PMID- 24076329
TI  - Birds of a feather... Generalization of facial structures following massive
      familiarization.
AB  - Three experiments examined the effects of symmetry and complexity, as facial
      structures, on the aesthetic judgments of faces, and how these effects are
      modulated by moderate or massive familiarization. Results showed that symmetrical
      faces were judged as more attractive than nonsymmetrical faces, and simple faces
      were judged as more attractive than complex faces-with complexity defined as the
      number of facial elements. Complexity in faces seemed to have overridden the
      usually positive effects of facial symmetry. Moreover, while moderate
      familiarization did not modulate the effects, massive familiarization to a
      specific face type resulted in structural generalization effects: participants
      provided higher aesthetic judgments to faces that were new, but similarly
      structured to those which they were familiarized. This latter result contrasts
      previous studies that have found structural contrast effects following
      familiarization to meaningless, abstract stimuli. Taken together, these results
      reflect the greater biological and social significance of faces as compared to
      other objects in the world. They also show that people are drawn to those with
      familiar characteristics. 

PMID- 24076330
TI  - The impact of domain-specific beliefs on decisions and causal judgments.
AB  - Extensive evidence suggests that people often rely on their causal beliefs in
      their decisions and causal judgments. To date, however, there is a dearth of
      research comparing the impact of causal beliefs in different domains. We
      conducted two experiments to map the influence of domain-specific causal beliefs
      on the evaluation of empirical evidence when making decisions and subsequent
      causal judgments. Participants made 120 decisions in a two-alternative forced
      choice task, framed in either a medical or a financial domain. Before each
      decision, participants could actively search for information about the outcome
      ("occurrence of a disease" or "decrease in a company's share price") on the basis
      of four cues. To analyze the strength of causal beliefs, we set two cues to have
      a generative relation to the outcome and two to have a preventive relation to the
      outcome. To examine the influence of empirical evidence, we manipulated the
      predictive power (i.e., cue validities) of the cues. Both experiments included a
      validity switch, where the four selectable cues switched from high to low
      validity or vice versa. Participants had to make a causal judgment about each cue
      before and after the validity switch. In the medical domain, participants stuck
      to the causal information in causal judgments, even when evidence was
      contradictory, while decisions showed an effect of both empirical and causal
      information. In contrast, in the financial domain, participants mainly adapted
      their decisions and judgments to the cue validities. We conclude that the
      strength of causal beliefs (1) is shaped by the domain, and (2) has a
      differential influence on the degree to which empirical evidence is taken into
      account in causal judgments and decision making. 

PMID- 24076331
TI  - Evidence for a response preparation bottleneck during dual-task performance:
      effect of a startling acoustic stimulus on the psychological refractory period.
AB  - The present study was designed to investigate the mechanism associated with dual
      task interference in a psychological refractory period (PRP) paradigm. We used a
      simple reaction time paradigm consisting of a vocal response (R1) and key-lift
      task (R2) with a stimulus onset asynchrony (SOA) between 100ms and 1500ms. On
      selected trials we implemented a startling acoustic stimulus concurrent with the
      second stimulus to determine if we could involuntarily trigger the second
      response. Our results indicated that the PRP delay in the second response was
      present for both control and startle trials at short SOAs, suggesting the second
      response was not prepared in advance. These results support a response
      preparation bottleneck and can be explained via a neural activation model of
      preparation. In addition, we found that the reflexive startle activation was
      reduced in the dual-task condition for all SOAs, a result we attribute to
      prepulse inhibition associated with dual-task processing. 

PMID- 24076332
TI  - Single-digit Arabic numbers do not automatically activate magnitude
      representations in adults or in children: evidence from the symbolic same
      different task.
AB  - We investigated whether the mere presentation of single-digit Arabic numbers
      activates their magnitude representations using a visually-presented symbolic
      same-different task for 20 adults and 15 children. Participants saw two single
      digit Arabic numbers on a screen and judged whether the numbers were the same or
      different. We examined whether reaction time in this task was primarily driven by
      (objective or subjective) perceptual similarity, or by the numerical difference
      between the two digits. We reasoned that, if Arabic numbers automatically
      activate magnitude representations, a numerical function would best predict
      reaction time; but if Arabic numbers do not automatically activate magnitude
      representations, a perceptual function would best predict reaction time. Linear
      regressions revealed that a perceptual function, specifically, subjective visual
      similarity, was the best and only significant predictor of reaction time in
      adults and in children. These data strongly suggest that, in this task, single
      digit Arabic numbers do not necessarily automatically activate magnitude
      representations in adults or in children. As the first study to date to
      explicitly study the developmental importance of perceptual factors in the
      symbolic same-different task, we found no significant differences between adults
      and children in their reliance on perceptual information in this task. Based on
      our findings, we propose that visual properties may play a key role in symbolic
      number judgements. 

PMID- 24076333
TI  - Cephalic secretion release in the male dwarf spider Oedothorax retusus
      (Linyphiidae: Erigoninae): an ultrastructural analysis.
AB  - Secondary sexual traits in males can extend to glandular structures that play a
      role during courtship and mating. In dwarf spiders (Linyphiidae, Erigoninae),
      glandular secondary sexual traits are particularly common. Males are
      characterized by cephalic modifications which produce secretions that females
      contact with their mouthparts during courtship and/or copulation. We used the
      dwarf spider Oedothorax retusus as a model species to investigate if and when the
      contents of the glands are released during a mating sequence and if so, if the
      gland reservoirs are refilled after mating. To this aim, we quantitatively
      compared the glandular tissue on the ultrastructural level between a)
      inexperienced males, b) males that performed courtship, c) males immediately
      after copulation, and d) males three days after mating. We assessed whether the
      treatment groups differed in the filling state of the conducting canals and
      receiving canals (reservoir regions) of the glandular units. Our study shows that
      courting males as well as males three days after mating did not differ
      significantly from control (inexperienced) males in the presence of secretions.
      However, males exhibited significantly less secretion immediately after mating.
      This strongly suggests that the main function of the secretions is gustatorial
      courtship and not the emission of volatile pheromones for mate attraction as was
      previously assumed. 

PMID- 24076334
TI  - High Laccase2 expression is likely involved in the formation of specific
      cuticular structures during soldier differentiation of the termite Reticulitermes
      speratus.
AB  - Termite soldiers are morphologically specialized for colony defense. Analysis of
      the mechanisms of soldier differentiation is important for understanding the
      establishment of termite societies. Soldiers differentiate from workers through a
      presoldier stage and have well-sclerotized and pigmented cuticles. These
      characteristics are important for nest defense and are likely to be caused by
      soldier-specific mechanisms of cuticular tanning. The molecular mechanisms
      leading to cuticular tanning have not been elucidated. Laccase2 (Lac2) plays
      important roles in this process in insects, and we hypothesized that Lac2
      expression may be involved in soldier-specific cuticular tanning. We observed
      inner and outer head cuticle changes and compared the Lac2 expression patterns
      among three molts (worker-worker, worker-presoldier and presoldier-soldier) in
      the termite Reticulitermes speratus. Quantitative analyses of head cuticle colors
      showed that the color properties changed more conspicuously in presoldier-soldier
      molts than in the other two molts. Histological observations showed that the
      exocuticles of soldier heads were substantially thicker than those of worker and
      presoldier heads, underwent tanning before or just after ecdysis, and were
      pigmented at earlier time points than other molts. Finally, markedly higher Lac2
      expression levels were observed just before and after ecdysis only in the
      presoldier-soldier molt. These results suggest that specific cuticular formation
      occurs in the exocuticles during soldier differentiation, and that the high level
      of Lac2 expression during the presoldier-soldier molt is related to soldier
      specific cuticular tanning. We speculate that evolution of the regulatory
      mechanisms of Lac2 expression were important for the acquisition of soldier
      specific cuticles. 

PMID- 24076335
TI  - Characterization of fluoxetine effects on ethanol withdrawal-induced cortical
      hyperexcitability by EEG spectral power in rats.
AB  - Antidepressants have been used for treatment of ethanol withdrawal symptoms
      mainly in observational studies. However, cortical frequency oscillation of
      ethanol withdrawal treatment with antidepressants remained to be elucidated. This
      study aimed to identify surrogate biomarkers that represent intact biological or
      ethanol withdrawal processes and response to pretreatment with fluoxetine, a
      selective serotonin reuptake inhibitor, with quantitative methods. Adult male
      Wistar rats implanted with electrodes over the frontal and parietal cortices were
      rendered dependent on ethanol via modified liquid diet (MLD) containing ethanol.
      Then, ethanol-containing MLD was replaced with isocaloric ethanol-free MLD to
      induce ethanol withdrawal symptoms. Locomotor activity, sleep-wakefulness and
      spectral frequencies of electroencephalographic (EEG) pattern during ethanol
      withdrawal period were analyzed. One-way ANOVA confirmed significant increases in
      locomotor activity and time spent in awake state and decreases time spent in non
      rapid eye movement (NREM) sleep and REM-sleep during ethanol withdrawal period.
      Fast Fourier Transformation also revealed predominant increases in gamma spectral
      powers within both the frontal and parietal cortices during ethanol withdrawal.
      However, these changes, except sleep-wake disturbances, were significantly
      attenuated by fluoxetine pretreatment (10 mg/kg). The present study supports the
      hypothesis that serotonergic hypofunction may underlie most of ethanol withdrawal
      symptoms and proposes that electroencephalographic patterns are valid biomarkers
      for ethanol withdrawal evaluation and treatment. 

PMID- 24076336
TI  - A role for tau at the synapse in Alzheimer's disease pathogenesis.
AB  - Alzheimer's disease (AD) is characterized by brain deposition of amyloid plaques
      and tau neurofibrillary tangles along with steady cognitive decline. Although the
      mechanism by which AD pathogenesis occurs is unclear, accumulating evidence
      suggests that dysfunction and loss of synaptic connections may be an early event
      underlying disease progression. Profound synapse degeneration is observed in AD,
      and the density of these connections strongly correlates with cognitive ability.
      Initial investigations into AD-related synaptic changes focused on the toxic
      effects of amyloid. However, recent research suggests an emerging role for tau at
      the synapse. Even in the absence of tangles, mice overexpressing human tau
      display significant synaptic degeneration, suggesting that soluble, oligomeric
      tau is the synaptotoxic species. However, the localization of tau within synapses
      in both healthy and AD brains indicates that tau might play a role in normal
      synaptic function, which may be disrupted in disease. Tau is able to impact
      synaptic activity in several ways: studies show tau interacting directly with
      post-synaptic signaling complexes, regulating glutamatergic receptor content in
      dendritic spines, and influencing targeting and function of synaptic
      mitochondria. Early trials of tau-targeted immunotherapy reduce tau pathology and
      synapse loss, indicating that the toxic effects of tau may be reversible within a
      certain time frame. Understanding the role of tau in both normal and degenerating
      synapses is crucial for the development of therapeutic strategies designed to
      ameliorate synapse loss and prevent AD pathogenesis. This article is part of the
      Special Issue entitled 'The Synaptic Basis of Neurodegenerative Disorders'. 

PMID- 24076338
TI  - Albumin for hyperacute stroke: another failed neuroprotectant.

PMID- 24076337
TI  - High-dose albumin treatment for acute ischaemic stroke (ALIAS) Part 2: a
      randomised, double-blind, phase 3, placebo-controlled trial.
AB  - BACKGROUND: In animal models of ischaemic stroke, 25% albumin reduced brain
      infarction and improved neurobehavioural outcome. In a pilot clinical trial,
      albumin doses as high as 2 g/kg were safely tolerated. We aimed to assess whether
      albumin given within 5 h of the onset of acute ischaemic stroke increased the
      proportion of patients with a favourable outcome. METHODS: We did a randomised,
      double-blind, parallel-group, phase 3, placebo-controlled trial between Feb 27,
      2009, and Sept 10, 2012, at 69 sites in the USA, 13 sites in Canada, two sites in
      Finland, and five sites in Israel. Patients aged 18-83 years with ischaemic (ie,
      non-haemorrhagic) stroke with a baseline National Institutes of Health stroke
      scale (NIHSS) score of 6 or more who could be treated within 5 h of onset were
      randomly assigned (1:1), via a central web-based randomisation process with a
      biased coin minimisation approach, to receive 25% albumin (2 g [8 mL] per kg;
      maximum dose 750 mL) or the equivalent volume of isotonic saline. All study
      personnel and participants were masked to the identity of the study drug. The
      primary endpoint was favourable outcome, defined as either a modified Rankin
      scale score of 0 or 1, or an NIHSS score of 0 or 1, or both, at 90 days. Analysis
      was by intention to treat. Thrombolytic therapies were permitted. This trial is
      registered with ClinicalTrials.gov, number NCT00235495. FINDINGS: 422
      participants were randomly assigned to receive albumin and 419 to receive saline.
      On Sept 12, 2012, the trial was stopped early for futility (n=841). The primary
      outcome did not differ between patients in the albumin group and those in the
      saline group (186 [44%] vs 185 [44%]; risk ratio 0.96, 95% CI 0.84-1.10, adjusted
      for baseline NIHSS score and thrombolysis stratum). Mild-to-moderate pulmonary
      oedema was more common in patients given albumin than in those given saline (54
      [13%] of 412 vs 5 [1%] of 412 patients); symptomatic intracranial haemorrhage
      within 24 h was also more common in patients in the albumin group than in the
      placebo group (17 [4%] of 415 vs 7 [2%] of 414 patients). Although the rate of
      favourable outcome in patients given albumin remained consistent at 44-45% over
      the course of the trial, the cumulative rate of favourable outcome in patients
      given saline rose steadily from 31% to 44%. INTERPRETATION: Our findings show no
      clinical benefit of 25% albumin in patients with ischaemic stroke; however, they
      should not discourage further efforts to identify effective strategies to protect
      the ischaemic brain, especially because of preclinical literature showing
      convincing proof-of-principle for the possibility of this outcome. FUNDING:
      National Institute of Neurological Disorders and Stroke, US National Institutes
      of Health; and Baxter Healthcare Corporation.

PMID- 24076339
TI  - Thyroid hormone-dependent development of the GABAergic pre- and post-synaptic
      components in the rat hippocampus.
AB  - Thyroid hormone (TH) plays essential roles in normal brain development mainly by
      regulating gene expression through binding to specific nuclear receptors which
      serve as transcription factors. Previous studies showed that perinatal deficiency
      of TH or impairment of its signaling severely affect brain development,
      especially the development of the gamma-aminobutyric acid (GABA) system, but
      cellular and molecular targets of the hormone are only partly uncovered. In the
      present study, we focused on the developing rat hippocampus which was confirmed
      to be one of the regions highly sensitive to TH status, and found two new targets
      of the hormone among the pre- and post-synaptic components of the GABAergic
      system. One was glutamic acid decarboxylase 65 (GAD65), the protein level of
      which was reduced to less than 50% of control in the hippocampus of hypothyroid
      rats (obtained by administering 0.025% methimazole in drinking water to pregnant
      dams from gestational day 15 until 4 weeks postpartum) and recovered to control
      levels by daily thyroxine-replacement after birth. Reduction in GAD65 protein was
      correlated immunohistochemically with a 37% reduction in the number of GAD65
      positive cells as well as a reduction in GAD65-positive processes. In contrast,
      the other GAD isotype, GAD67, was not affected by TH status. A subpopulation of
      GABAergic neurons containing parvalbumin was also confirmed to be highly
      dependent on TH status. The second target of thyroid hormone was neuron-specific
      K(+)/Cl(-) co-transporter, KCC2, which is responsible for switching of GABA
      action from excitatory to inhibitory. In the euthyroid hippocampus, a sharp rise
      of kcc2 expression was observed at postnatal day (PND)10 which was followed by a
      large increase in KCC2 protein at PND15. This transient rise in kcc2 expression
      was completely suppressed by hypothyroidism, resulting in nearly 80% reduction in
      KCC2 protein at PND15. These results indicate that the development of GABAergic
      terminals and the excitatory to inhibitory maturation of GABA signaling are
      strongly dependent on TH. 

PMID- 24076340
TI  - Co-delivery of viral proteins and a TLR7 agonist from polysaccharide
      nanocapsules: a needle-free vaccination strategy.
AB  - Here we report a new nanotechnology-based nasal vaccination concept intended to
      elicit both, specific humoral and cellular immune responses. The concept relies
      on the use of a multifunctional antigen nanocarrier consisting of a hydrophobic
      nanocore, which can allocate lipophilic immunostimulants, and a polymeric corona
      made of chitosan (CS), intended to associate antigens and facilitate their
      transport across the nasal mucosa. The Toll-like receptor 7 (TLR7) agonist,
      imiquimod, and the recombinant hepatitis B surface antigen (HB), were selected as
      model molecules for the validation of the concept. The multifunctional
      nanocarriers had a nanometric size (around 200 nm), a high positive zeta
      potential (+45 mV) and a high antigen association efficiency (70%). They also
      exhibited the ability to enter macrophages in vitro and to effectively deliver
      the associated imiquimod intracellularly, as noted by the secretion of pro
      inflammatory cytokines (i.e. IL-6 and TNF-alpha). However, the nanocarriers did
      not induce the in vitro activation of the complement cascade. Finally, the
      positive effect of the co-delivery of HB and imiquimod from the nanocapsules was
      evidenced upon intranasal administration to mice. The nanocapsules containing
      imiquimod elicited a protective immune response characterized by increasing IgG
      levels over time and specific immunological memory. Additionally, the levels of
      serum IgG subclasses (IgG1 and IgG2a) indicated a balanced cellular/humoral
      response, thus suggesting the capacity of the nanocapsules to modulate the
      systemic immune response upon nasal vaccination.

PMID- 24076341
TI  - User-centered design in brain-computer interfaces-a case study.
AB  - OBJECTIVE: The array of available brain-computer interface (BCI) paradigms has
      continued to grow, and so has the corresponding set of machine learning methods
      which are at the core of BCI systems. The latter have evolved to provide more
      robust data analysis solutions, and as a consequence the proportion of healthy
      BCI users who can use a BCI successfully is growing. With this development the
      chances have increased that the needs and abilities of specific patients, the end
      users, can be covered by an existing BCI approach. However, most end-users who
      have experienced the use of a BCI system at all have encountered a single
      paradigm only. This paradigm is typically the one that is being tested in the
      study that the end-user happens to be enrolled in, along with other end-users.
      Though this corresponds to the preferred study arrangement for basic research, it
      does not ensure that the end-user experiences a working BCI. In this study, a
      different approach was taken; that of a user-centered design. It is the
      prevailing process in traditional assistive technology. Given an individual user
      with a particular clinical profile, several available BCI approaches are tested
      and - if necessary - adapted to him/her until a suitable BCI system is found.
      METHODS: Described is the case of a 48-year-old woman who suffered from an
      ischemic brain stem stroke, leading to a severe motor- and communication deficit.
      She was enrolled in studies with two different BCI systems before a suitable
      system was found. The first was an auditory event-related potential (ERP)
      paradigm and the second a visual ERP paradigm, both of which are established in
      literature. RESULTS: The auditory paradigm did not work successfully, despite
      favorable preconditions. The visual paradigm worked flawlessly, as found over
      several sessions. This discrepancy in performance can possibly be explained by
      the user's clinical deficit in several key neuropsychological indicators, such as
      attention and working memory. While the auditory paradigm relies on both
      categories, the visual paradigm could be used with lower cognitive workload.
      Besides attention and working memory, several other neurophysiological and 
      psychological indicators - and the role they play in the BCIs at hand - are
      discussed. CONCLUSION: The user's performance on the first BCI paradigm would
      typically have excluded her from further ERP-based BCI studies. However, this
      study clearly shows that, with the numerous paradigms now at our disposal, the
      pursuit for a functioning BCI system should not be stopped after an initial
      failed attempt.

PMID- 24076342
TI  - The auditory P300-based single-switch brain-computer interface: paradigm
      transition from healthy subjects to minimally conscious patients.
AB  - OBJECTIVE: Within this work an auditory P300 brain-computer interface based on
      tone stream segregation, which allows for binary decisions, was developed and
      evaluated. METHODS AND MATERIALS: Two tone streams consisting of short beep tones
      with infrequently appearing deviant tones at random positions were used as
      stimuli. This paradigm was evaluated in 10 healthy subjects and applied to 12
      patients in a minimally conscious state (MCS) at clinics in Graz, Wurzburg, Rome,
      and Liege. A stepwise linear discriminant analysis classifier with 10*10 cross
      validation was used to detect the presence of any P300 and to investigate
      attentional modulation of the P300 amplitude. RESULTS: The results for healthy
      subjects were promising and most classification results were better than random.
      In 8 of the 10 subjects, focused attention on at least one of the tone streams
      could be detected on a single-trial basis. By averaging 10 data segments,
      classification accuracies up to 90.6% could be reached. However, for MCS patients
      only a small number of classification results were above chance level and none of
      the results were sufficient for communication purposes. Nevertheless, signs of
      consciousness were detected in 9 of the 12 patients, not on a single-trial basis,
      but after averaging of all corresponding data segments and computing significant
      differences. These significant results, however, strongly varied across sessions
      and conditions. CONCLUSION: This work shows the transition of a paradigm from
      healthy subjects to MCS patients. Promising results with healthy subjects are,
      however, no guarantee of good results with patients. Therefore, more
      investigations are required before any definite conclusions about the usability
      of this paradigm for MCS patients can be drawn. Nevertheless, this paradigm might
      offer an opportunity to support bedside clinical assessment of MCS patients and
      eventually, to provide them with a means of communication.

PMID- 24076343
TI  - Facing the challenge: bringing brain-computer interfaces to end-users.

PMID- 24076344
TI  - Correlation between operative and histological excision margins for cutaneous
      squamous cell carcinomas.

PMID- 24076345
TI  - Vascularised toe proximal interphalangeal joint transfer in posttraumatic finger
      joint reconstruction: the effect of skin paddle design on extensor lag.
AB  - Vascularised joint transfer (VJT) from the toe proximal interphalangeal joint
      (PIPJ) has been criticised for providing a limited range of motion (ROM) and
      significant extensor lag in reconstructed digits. The original technique includes
      the dorsal skin of toe PIPJ as a marker of joint viability, while a modified
      technique uses the skin flap of the great toe and the dorsal foot. This
      systematic review aimed to assess vascularised toe-to-finger PIPJ transfers with
      respect to functional outcomes, and in particular, whether a modified skin paddle
      design can improve extensor lag. METHODS: A MEDLINE search was performed. Studies
      were included if they present five or more vascularised toe-to-finger PIPJ
      transfers for posttraumatic reconstruction, and with the functional outcome data
      available. RESULTS: Seven studies including 92 VJTs met the inclusion criteria.
      The overall survival rate was 93.5%. Among the successful 86 VJTs, mean single
      joint ROM was 37.4 +/- 21.1 degrees , with a mean extension lag of 31.8 +/- 18.8
      degrees  and a mean flexion of 69.2 +/- 22.8 degrees . The traditional group with
      the skin paddle taken from the dorsum of the toe PIPJ had a statistically
      significantly greater extensor lag than the modified group with the skin paddle
      harvested from the great toe and dorsal foot (37.8 degrees  vs. 17.1 degrees , p
      < 0.001). The secondary variable of interest was age of the patient at time of
      transfer (children vs. adults). There was no significant difference in ROM
      between younger (<=16 years) and older patients (>16 years). CONCLUSIONS: This
      systematic review suggests that extensor lag may be improved by using the
      modified skin paddle design by harvesting it from the great toe and the dorsal
      foot. This effect may be mediated by the preservation of the native extensor
      tendon apparatus in the finger.

PMID- 24076346
TI  - Was it really Radiesse or whose algorithm is better?

PMID- 24076347
TI  - A simple and effective all-inside repair for FDP in zone 1.

PMID- 24076348
TI  - Involvement of the spinal NALP1 inflammasome in neuropathic pain and aspirin
      triggered-15-epi-lipoxin A4 induced analgesia.
AB  - Neuroinflammation plays an important role in nerve-injury-induced neuropathic
      pain, but the explicit molecular mechanisms of neuroinflammation in neuropathic
      pain remain unclear. As one of the most critical inflammatory cytokines,
      interleukin-1beta (IL-1beta) has been regarded as broadly involved in the
      pathology of neuropathic pain. The inflammasome caspase-1 platform is one primary
      mechanism responsible for the maturation of IL-1beta. Lipoxins, a type of
      endogenous anti-inflammatory lipid, have proved to be effective in relieving
      neuropathic pain behaviors. The present study was designed to examine whether the
      inflammasome caspase-1 IL-1beta platform is involved in chronic constriction
      injury (CCI)-induced neuropathic pain and in lipoxin-induced analgesia. After
      rats were subjected to the CCI surgery, mature IL-1beta was significantly
      increased in the ipsilateral spinal cord, and the inflammasome platform
      consisting of NALP1 (NAcht leucine-rich-repeat protein 1), caspase-1 and ASC
      (apoptosis-associated speck-like protein containing a caspase-activating
      recruitment domain) was also activated in spinal astrocytes and neurons,
      especially at the superficial laminae of the spinal dorsal horn; The aspirin
      triggered-15-epi-lipoxin A4 (ATL), which shares the potent actions of the
      endogenous lipoxins, was administered to the CCI rats. Repeated intrathecal
      injection with ATL markedly attenuated the CCI-induced thermal hyperalgesia and
      significantly inhibited NALP1 inflammasome activation, caspase-1 cleavage, and IL
      1beta maturation. These results suggested that spinal NALP1 inflammasome was
      involved in the CCI-induced neuropathic pain and that the analgesic effect of ATL
      was associated with suppressing NALP1 inflammasome activation. 

PMID- 24076349
TI  - Hesperidin pretreatment protects hypoxia-ischemic brain injury in neonatal rat.
AB  - Neonatal hypoxia-ischemic encephalopathy (HIE) remains a major cause of brain
      damage, leading to high disability and mortality rates in neonates. In vitro
      studies have shown that hesperidin, a flavanone glycoside found abundantly in
      citrus fruits, acts as an antioxidant. Although hesperidin has been considered as
      a potential treatment for HIE, its effects have not been fully evaluated. In this
      study, the protective effect of hesperidin pretreatment against hypoxia-ischemic
      (HI) brain injury and possible signal pathways were investigated using in vivo
      and in vitro models. In vivo HI model employed unilateral carotid ligation in
      postnatal day 7 rat with exposure to 8% hypoxia for 2.5h, whereas in vitro model
      employed primary cortical neurons of neonatal rats subjected to oxygen and
      glucose deprivation for 2.5h. Hesperidin pretreatment significantly reduced HI
      induced brain tissue loss and improved neurological outcomes as shown in 2,3,5
      triphenyltetrazolium chloride monohydrate staining and foot-fault results. The
      neuroprotective effects of hesperidin are likely the results of preventing an
      increase in intracellular reactive oxygen species and lipid peroxide levels.
      Hesperidin treatment also activated a key survival signaling kinase, Akt, and
      suppressed the P-FoxO3 level. Hesperidin pretreatment protected neonatal HIE by
      reducing free radicals and activating phosphorylated Akt. 

PMID- 24076350
TI  - SCN1A rs3812718 polymorphism and susceptibility to epilepsy with febrile
      seizures: a meta-analysis.
AB  - BACKGROUND: Evidence showed that the SCN1A IVS5N+5G>A polymorphism might be
      associated with susceptibility to epilepsy with febrile seizures (EFS), however,
      the published data were inconclusive. Therefore, a meta-analysis was performed to
      estimate the overall EFS risk with the polymorphism. METHODS: The PubMed and
      Medline were searched up to March, 2013 for studies on the association between
      SCN1A IVS5N+5G>A polymorphism and EFS risk. Odds ratios (ORs) and 95% confidence
      intervals (CIs) were estimated by means of a genetic model free approach. The
      heterogeneity and sensitivity of each report and the publication bias were also
      performed. All the statistical analyses were done using the STATA 11.0 software.
      RESULT: A total of 6 studies with 2719 cases and 2317 controls met the selection
      criteria. We found significant association between SCN1A polymorphism and EFS (A
      vs. G: OR=1.498, 95%CI=1.138-1.972; AA vs. GG: OR=2.292, 95%CI=1.620-3.243; AG
      vs. GG: OR=1.414, 95%CI=1.010-1.978; recessive model: OR=1.747, 95%CI=1.119-2.728
      and dominant model: OR=1.730, 95%CI=1.259-2.376). When compared with the epilepsy
      without febrile seizure (EWFS), the subgroup analysis stratified by ethnicity
      showed that the SNP was significantly associated with EFS in Caucasian (A vs. G:
      OR=1.505, 95%CI=1.218-1.861; AA vs. GG: OR=2.081, 95%CI=1.358-3.189; recessive
      model: OR=1.715, 95%CI=1.273-2.310 and dominant model: OR=1.625, 95%CI=1.096
      2.410), but not in Indian and Chinese. When applying Bonferroni correction
      (significance was set at 0.05/20), the Caucasian still has robust association
      with EFS and epilepsy. CONCLUSION: The present meta-analysis suggests that SCN1A
      IVS5N+5G>A polymorphism is a risk factor of EFS and epilepsy, especially in
      Caucasian.

PMID- 24076351
TI  - GALNT11 as a new molecular marker in chronic lymphocytic leukemia.
AB  - Aberrant mucin O-glycosylation often occurs in different cancers and is
      characterized by immature expression of simple mucin-type carbohydrates. At
      present, there are some controversial reports about the Tn antigen (GalNAcalpha-O
      Ser/Thr) expression and there is a great lack of information about the [UDP-N
      acetyl-alpha-d-galactosamine:polypeptide N-acetylgalactosaminyltransferase
      (GalNAc-Ts)] expression in chronic lymphocytic leukemia (CLL). To gain insight in
      these issues we evaluated the Tn antigen expression in CLL patient samples using
      two Tn binding proteins with different fine specificity. We also studied the
      expression from 14 GalNAc-Ts genes in CLL patients by RT-PCR. Our results have
      provided additional information about the expression level of the Tn antigen,
      suggesting that a low density of Tn residues is expressed in CLL cells. We also
      found that GALNT11 was expressed in CLL cells and normal T cell whereas little or
      no expression was found in normal B cells. Based on these results, GALNT11
      expression was assessed by qPCR in a cohort of 50 CLL patients. We found
      significant over-expression of GALNT11 in 96% of B-CLL cells when compared to
      normal B cells. Moreover, we confirmed the expression of this enzyme at the
      protein level. Finally we found that GALNT11 expression was significantly
      associated with the mutational status of the immunoglobulin heavy chain variable
      region (IGHV), [?(2)(1)=18.26; P<0.0001], lipoprotein lipase expression
      [?(2)(1)=13.72; P=0.0002] and disease prognosis [?(2)(1)=15.49; P<0.0001]. Our
      evidence suggests that CLL patient samples harbor aberrant O-glycosylation
      highlighted by Tn antigen expression and that the over-expression of GALNT11
      constitutes a new molecular marker for CLL. 

PMID- 24076352
TI  - Uncoupling of osteoblast-osteoclast regulation in a chemical murine model of
      Gaucher disease.
AB  - Gaucher disease (GD) is caused by mutations in the GBA gene that confer a
      deficient level of activity of glucocerebrosidase (GCase). This deficiency leads
      to accumulation of the glycolipid glucocerebroside in the lysosomes of cells of
      monocyte/macrophage system. Type I GD is the mildest form and is characterized by
      the absence of neuronopathic affection. Bone compromise in Gaucher disease
      patients is the most disabling aspect of the disease. However, pathophysiological
      aspects of skeletal alterations are still poorly understood. The homeostasis of
      bone tissue is maintained by the balanced processes of bone resorption by
      osteoclasts and formation by osteoblasts. We decided to test whether bone
      resorption and/or bone formation could be altered by the use of a chemical in
      vitro murine model of Gaucher disease. We used two sources of cells from
      monocyte/macrophages lineage isolated from normal mice, splenocytes (S) and
      peritoneal macrophages (PM), and were exposed to CBE, the inhibitor of GCase (S
      CBE and PM-CBE, respectively). Addition of both conditioned media (CM) from S-CBE
      and PM-CBE induced the differentiation of osteoclasts precursors from bone marrow
      to mature and functional osteoclasts. TNF-alpha could be one of the factors
      responsible for this effect. On the other hand, addition of CM to an osteoblast
      cell culture resulted in a reduction in expression of alkaline phosphatase and
      mineralization process. In conclusion, these results suggest implication of
      changes in both bone formation and bone resorption and are consistent with the
      idea that both sides of the homeostatic balance are affected in GD.

PMID- 24076353
TI  - Angiotensin converting enzyme insertion/deletion polymorphism is associated with
      increased adiposity and blood pressure in obese children and adolescents.
AB  - BACKGROUND: The insertion/deletion polymorphism in the gene encoding the
      angiotensin-converting enzyme (ACE I/D) was associated with arterial hypertension
      and obesity in adults, but the data in children are scarce and yielded
      contrasting results. We assessed the impact of the ACE I/D on blood pressure and
      obesity related traits in a Brazilian cohort of obese children and adolescents.
      METHODS AND RESULTS: ACE I/D was genotyped in 320 obese children and adolescents
      (64% of girls) aged 7-16years, referred for a weight-loss program. We observed an
      association of the D-allele with blood pressure and with pre
      hypertension/hypertension in boys (odds ratio 2.44, 95% C.I. 1.34-4.68, p=0.005
      for a codominant model). The D-allele, insulin resistance and body fat mass had
      independent and additive effects and explained 14% of the variance of pre
      hypertension/hypertension. The BMI, waist circumference, and body fat mass were
      significantly higher in DD/ID boys than in II boys (p<0.005). Allelic
      associations with obesity related traits were independent of the association with
      blood pressure. No genotype associations were observed in girls. CONCLUSIONS: The
      D-allele of the ACE I/D polymorphism was associated with arterial hypertension
      and with obesity related traits in boys, but not in girls, in a cohort of obese
      children and adolescents. These associations were independent of each other, as
      well as of the effects of other confounding traits such as insulin secretion,
      insulin sensitivity and glucose tolerance. Our results are in agreement with
      experimental evidences suggesting that the renin-angiotensin system plays a role
      in the regulation of visceral adipose tissue accumulation.

PMID- 24076354
TI  - Identification and expression analysis of the leukocyte cell-derived chemotaxin-2
      (LECT2) gene in duck (Anas platyrhynchos).
AB  - Leukocyte cell-derived chemotaxin 2 (LECT2), first identified as a chemotactic
      factor, is involved in the regulation of liver regeneration, carcinogenesis, and
      natural killer T-cell homeostasis in mammals. The function of LECT2 in the duck
      remains unclear, however. A suppression subtractive cDNA library was constructed
      from the livers of 3-day-old ducklings treated with duck hepatitis virus type I
      (DHV-1). A total of 66 expressed sequence tags (ESTs) were identified in the
      libraries. Among the novel gene fragments identified was the LECT2 gene. Full
      length duck LECT2 (duLECT2) complementary DNA (cDNA) was obtained using the
      reverse transcription-polymerase chain reaction (RT-PCR) and rapid amplification
      of the cDNA ends (RACE). The cDNA consisted of a 50 nucleotide 5' untranslated
      region (UTR), an 84 nucleotide 3' UTR, and a 1020 nucleotide open reading frame
      encoding a single protein of 339 amino acids. In agreement with a previously
      reported LECT2 sequence, the predicted amino acid sequence contains
      characteristic phosphorylation and N-glycosylation sites. DuLECT2 is highly
      similar to LECT2 genes from other vertebrates. Phylogenetic analysis demonstrated
      that the LECT2 gene has been highly conserved throughout vertebrate evolution. RT
      PCR analyses revealed that duLECT2 mRNA is widely expressed in healthy tissues.
      They also showed that duLECT2 mRNA is significantly up-regulated in the liver and
      spleen following injection with DHV-1 or polyriboinosinic polyribocytidylic acid
      (poly I:C), peaking 4 or 12h post-challenge in the liver and spleen,
      respectively, and afterwards gradually returning to normal. Our findings suggest
      that duLECT2 contributes to the innate immune response against viral infections. 

PMID- 24076355
TI  - Identification of differentially-expressed genes potentially implicated in
      drought response in pitaya (Hylocereus undatus) by suppression subtractive
      hybridization and cDNA microarray analysis.
AB  - Drought is one of the most severe threats to the growth, development and yield of
      plant. In order to unravel the molecular basis underlying the high tolerance of
      pitaya (Hylocereus undatus) to drought stress, suppression subtractive
      hybridization (SSH) and cDNA microarray approaches were firstly combined to
      identify the potential important or novel genes involved in the plant responses
      to drought stress. The forward (drought over drought-free) and reverse (drought
      free over drought) suppression subtractive cDNA libraries were constructed using
      in vitro shoots of cultivar 'Zihonglong' exposed to drought stress and drought
      free (control). A total of 2112 clones, among which half were from either forward
      or reverse SSH library, were randomly picked up to construct a pitaya cDNA
      microarray. Microarray analysis was carried out to verify the expression
      fluctuations of this set of clones upon drought treatment compared with the
      controls. A total of 309 expressed sequence tags (ESTs), 153 from forward library
      and 156 from reverse library, were obtained, and 138 unique ESTs were identified
      after sequencing by clustering and blast analyses, which included genes that had
      been previously reported as responsive to water stress as well as some
      functionally unknown genes. Thirty six genes were mapped to 47 KEGG pathways,
      including carbohydrate metabolism, lipid metabolism, energy metabolism,
      nucleotide metabolism, and amino acid metabolism of pitaya. Expression analysis
      of the selected ESTs by reverse transcriptase polymerase chain reaction (RT-PCR)
      corroborated the results of differential screening. Moreover, time-course
      expression patterns of these selected ESTs further confirmed that they were
      closely responsive to drought treatment. Among the differentially expressed genes
      (DEGs), many are related to stress tolerances including drought tolerance.
      Thereby, the mechanism of drought tolerance of this pitaya genotype is a very
      complex physiological and biochemical process, in which multiple metabolism
      pathways and many genes were implicated. The data gained herein provide an
      insight into the mechanism underlying the drought stress tolerance of pitaya, as
      well as may facilitate the screening of candidate genes for drought tolerance. 

PMID- 24076356
TI  - Molecular cloning, characterization and expression of myoglobin in Tibetan
      antelope (Pantholops hodgsonii), a species with hypoxic tolerance.
AB  - The Tibetan antelope (Pantholops hodgsonii) is a hypoxia-tolerant species that
      lives at an altitude of 4,000-5,000 m above sea level on the Qinghai-Tibetan
      plateau. Myoglobin is an oxygen-binding cytoplasmic hemoprotein that is
      abundantly expressed in oxidative skeletal and cardiac myocytes. Numerous studies
      have implicated that hypoxia regulates myoglobin expression to allow adaptation
      to conditions of hypoxic stress. Few studies have yet looked at the effect of
      myoglobin on the adaptation to severe environmental stress on TA. To investigate
      how the Tibetan antelope (TA) has adapted to a high altitude environment at the
      molecular level, we cloned and analyzed the myoglobin gene from TA, compared the
      expression of myoglobin mRNA and protein in cardiac and skeletal muscle between
      TA and low altitude sheep. The results indicated that the full-length myoglobin
      cDNA is composed of 1154 bp with a 111 bp 5' untranslated region (UTR), a 578 bp
      3' UTR and a 465 bp open reading frame (ORF) encoding a polypeptide of 154 amino
      acid residues with a predicted molecular weight of 17.05 kD. The TA myoglobin
      cDNA sequence and the deduced amino acid sequence were highly homologous with
      that of other species. When comparing the myoglobin sequence from TA with the
      Ovis aries myoglobin sequence, variations were observed at codons 21 (GGT->GAT)
      and 78 (GAA->AAG), and these variations lead to changes in the corresponding
      amino acids, i.e., Gly->Asp and Glu->Lys, respectively. But these amino acid
      substitutions are unlikely to effect the ability of binding oxygen because their
      location is less important, which is revealed by the secondary structure and 3D
      structure of TA myoglobin elaborated by homology modeling. However, the results
      of myoglobin expression in cardiac and skeletal muscles showed that they were
      both significantly higher than that in plain sheep not only in mRNA but also
      protein level. We speculated that the higher expression of myoglobin in TA
      cardiac and skeletal muscles improves their ability to obtain and store oxygen
      under hypoxic conditions. This study indicated that TA didn't improve the ability
      of carrying oxygen by changing the molecular structure of myoglobin, but through
      increasing the expression of myoglobin in cardiac and skeletal muscles.

PMID- 24076357
TI  - Inhibition of primary clinical isolates of human parainfluenza virus by DAS181 in
      cell culture and in a cotton rat model.
AB  - DAS181 is a novel drug in development for the treatment of influenza as well as
      human parainfluenza viruses (hPIVs). Previous studies demonstrated that DAS181
      inhibited laboratory strains of hPIV, but no tests were conducted with primary
      clinical isolates of hPIV. To fill this gap, we studied six primary isolates
      including hPIV-2 and hPIV-3. First tests showed that the amplification of all
      viruses in vitro was reproducibly inhibited with DAS181 drug concentrations
      ranging between 0.1 and 1nM. An hPIV-3 primary clinical isolate was then tested
      in a cotton rat model for sensitivity to 0.3-1mg/kg drug treatments. Results
      showed that virus amplification in the lower respiratory tract was significantly
      and reproducibly inhibited by drug. Together, experiments demonstrated that
      DAS181 inhibited primary clinical isolates of hPIV in vitro and in vivo at doses
      similar to those previously described for inhibition of laboratory hPIV and
      influenza virus isolates. 

PMID- 24076358
TI  - Ten years of dengue drug discovery: progress and prospects.
AB  - To combat neglected diseases, the Novartis Institute of Tropical Diseases (NITD)
      was founded in 2002 through private-public funding from Novartis and the
      Singapore Economic Development Board. One of NITD's missions is to develop
      antivirals for dengue virus (DENV), the most prevalent mosquito-borne viral
      pathogen. Neither vaccine nor antiviral is currently available for DENV. Here we
      review the progress in dengue drug discovery made at NITD as well as the major
      discoveries made by academia and other companies. Four strategies have been
      pursued to identify inhibitors of DENV through targeting both viral and host
      proteins: (i) HTS (high-throughput screening) using virus replication assays;
      (ii) HTS using viral enzyme assays; (iii) structure-based in silico docking and
      rational design; (iv) repurposing hepatitis C virus inhibitors for DENV. Along
      the developmental process from hit finding to clinical candidate, many inhibitors
      did not advance beyond the stage of hit-to-lead optimization, due to their poor
      selectivity, physiochemical or pharmacokinetic properties. Only a few compounds
      showed efficacy in the AG129 DENV mouse model. Two nucleoside analogs, NITD-008
      and Balapiravir, entered preclinical animal safety study and clinic trial, but
      both were terminated due to toxicity and lack of potency, respectively.
      Celgosivir, a host alpha-glucosidase inhibitor, is currently under clinical
      trial; its clinical efficacy remains to be determined. The knowledge accumulated
      during the past decade has provided a better rationale for ongoing dengue drug
      discovery. Though challenging, we are optimistic that this continuous, concerted
      effort will lead to an effective dengue therapy. 

PMID- 24076359
TI  - The impact of anxiety and depression on patients within a large type 1 diabetes
      insulin pump population. An observational study.
AB  - BACKGROUND: Continuous subcutaneous insulin infusion (CSII) is generally
      successful for patients with type 1 diabetes in improving glycaemic control,
      alleviating the burden of hypoglycaemia and improving the quality of life. There
      is however, a cohort of patients who fail to thrive on pump therapy and
      psychological factors or "brittleness" have been posited as a cause for this. We
      aimed to assess the extent and spectrum of psychological illness in a population
      of pump patients. METHODS: We analysed the patient data and records of 350
      patients with type 1 diabetes who formed the insulin pump patient population from
      a large teaching hospital and compared them with an age and sex matched reference
      population of patients with type 1 diabetes. We quantified the prevalence of
      anxiety and depression before and after the initiation of pump therapy and looked
      to see whether this had implications for changes in glycaemic control and
      hypoglycaemia reduction. RESULTS: Mental health problems amongst patients
      selected for CSII occur significantly more frequently than in a matched
      population with type 1 diabetes (51% vs 40%, P<0.05). Depression and anxiety were
      more prevalent in the CSII group. Of those with mental health problems, there is
      a tendency to do less well in terms of improvements in glycaemic control as
      indicated by changes in HbA(1c) and hypoglycaemia reduction--the latter most
      notable in patients with co-existent depression. CONCLUSIONS: The incidence and
      prevalence of mental health problems in individuals with diabetes is greater than
      that of the general population. In patients who are selected to go onto insulin
      pump therapy, the incidence is again greater. We have shown that in those with
      psychological illness, they tend to do less well in terms of improving their
      overall diabetes control. These results suggest that CSII may not be a suitable
      route of therapy alone for all of those who would fulfill the traditional
      criteria and suggest that psychological assessment, therapy and intervention may
      be an altogether more appropriate or alternative or adjunctive course of action
      in supporting their diabetes self management. The wider implication is that all
      the patients with diabetes should be regularly assessed for psychological
      problems and that there needs to be greater psychology/psychiatric support
      available to intensive diabetes clinics, especially as part of a pre-pump
      pathway.

PMID- 24076360
TI  - Influence of migration on characteristics of type 2 diabetes in sub-Saharan
      Africans.
AB  - AIM: This study compared the clinical and biochemical characteristics and
      microvascular complications found in three groups of type 2 diabetes (T2D)
      patients: Africans living in Africa; African immigrants living in France; and
      Caucasians living in France. METHODS: Diagnosed T2D Africans living in Cameroon
      (n=100) were compared with 98 African migrants diagnosed with T2D after having
      moved to France, and a group of 199 T2D Caucasian patients living in France. All
      underwent clinical and biochemical evaluations, and all were assessed for
      microvascular complications. RESULTS: The median duration of stay of the migrants
      in France was 15years before being diagnosed with diabetes. Despite similar
      durations of diagnosis, they were 8.9years younger at the time of diagnosis than
      Africans living in Cameroon (P<0.001). Caucasians and African immigrants in
      France had lower HbA1c values than Africans in Cameroon (P<0.001); they were also
      more aggressively treated for hypertension and dyslipidaemia and, therefore, had
      significantly lower blood pressure levels and better lipid profiles. Diabetic
      nephropathy and retinopathy rates were higher in Cameroon than in the two other
      groups. After adjusting for age, diabetes duration, HbA1c, hypertension and other
      covariates, only the prevalence of diabetic nephropathy (OR: 5.61, 95% CI: 2.32
      13.53; P<0.0001) was higher in Cameroon compared with those living in France.
      CONCLUSION: Our results suggest that Africans who emigrate to France may develop
      diabetes earlier than those staying in their home country. However, the latter
      may be a reflection of late diagnosis of diabetes. Also, the less adequate
      diabetes and hypertension control in the latter would explain their higher rates
      of nephropathy. Large-scale cohorts are now warranted to substantiate these
      observations.

PMID- 24076361
TI  - A novel method for the identification of factors involved in host-pathogen
      interactions in Drosophila melanogaster.
AB  - A new method was established, standardized and validated for screening factors
      involved in the response to septic injury in Drosophila melanogaster. The method,
      based on inducing lesion by removing the tarsal segments of the first pair of
      legs of Drosophila adults and exposing them to different bacteria, imitates
      injury that often occurs in the natural habitat. The method is easy to perform,
      highly reproducible and suitable for large-scale genetic screens with the aim of
      identifying factors involved in host-pathogen interactions. The technique was
      validated by using mutant variations of different components of the immune
      response, blood clotting as well as the involvement of a number of genes known to
      be instrumental in the humoral and cell-mediated immune responses of Drosophila
      was confirmed. Moreover, the combination of the present method with antibiotic
      treatment allows the screening of potential antimicrobial drugs in vivo. 

PMID- 24076362
TI  - Carotenoids.

PMID- 24076363
TI  - Body mass index in childhood and adult risk of primary liver cancer.
AB  - BACKGROUND & AIMS: Childhood overweight increases the risk of early development
      of non-alcoholic fatty liver disease, which may predispose to carcinogenesis. We
      investigated if childhood body size during school ages was associated with the
      risk of primary liver cancer in adults. METHODS: A cohort of 285,884 boys and
      girls, born 1930 through 1980, who attended school in Copenhagen, were followed
      from 1977 to 31 December 2010. Their heights and weights were measured by school
      doctors or nurses at ages 7 through 13 years. Body mass index (BMI) z-scores were
      calculated from an internal age- and sex-specific reference. Information on liver
      cancer was obtained from the National Cancer Registry. Hazard ratios and 95%
      confidence intervals (95% CI) of liver cancer were estimated by Cox regression.
      RESULTS: During 6,963,105 person-years of follow-up, 438 cases of primary liver
      cancer were recorded. The hazard ratio (95% CI) of adult liver cancer was 1.20
      (1.07-1.33) and 1.30 (1.16-1.46) per 1-unit BMI z-score at 7 years and 13 years
      of age, respectively. Similar associations were found in boys and girls, for
      hepatocellular carcinoma only, across years of birth, and after accounting for
      diagnoses of viral hepatitis, alcohol-related disorders, and biliary cirrhosis.
      CONCLUSIONS: Higher BMI in childhood increases the risk of primary liver cancer
      in adults. In view of the high case fatality of primary liver cancer, this result
      adds to the future negative health outcomes of the epidemic of childhood
      overweight, reinforcing the need for its prevention.

PMID- 24076364
TI  - The changing role of beta-blocker therapy in patients with cirrhosis.
AB  - Cirrhosis is a leading cause of death in the United States and worldwide. Beta
      blockers have been established in numerous studies as part of the cornerstone of
      the medical management of cirrhosis, particularly in the primary and secondary
      prevention of variceal hemorrhage. However, new evidence has cautioned the use of
      beta-blockers in patients with end-stage cirrhosis and refractory ascites. In
      this article, we review the beneficial effects of beta-blocker therapy, the
      potential harms of aggressive beta-blocker therapy, and provide suggestions
      regarding the appropriate use of this class of medications in patients with
      cirrhosis. 

PMID- 24076365
TI  - The iron-induced cysteine proteinase TvCP4 plays a key role in Trichomonas
      vaginalis haemolysis.
AB  - Trichomonas vaginalis has multiple proteinases, mainly of the cysteine type
      (CPs), including a 34 kDa precursor cathepsin L-like CP dubbed TvCP4. TvCP4 is an
      iron-up-regulated CP. The goal of this work was to identify the role of TvCP4 in
      the virulence of T. vaginalis. We cloned, expressed, and purified the recombinant
      mature enzyme region of TvCP4 (TvCP4r) to produce a rabbit polyclonal antibody
      (alpha-TvCP4r). This antibody reacted with a ~24 kDa protein band in total
      protein extracts that could correspond to the mature enzyme. By two-dimensional
      western blot assays TvCP4 corresponded to three protein spots of ~24 kDa with pI
      values of ~6.7, 6.9, and 7.0 and two spots of ~22 and ~21 kDa with a pI of 6.9,
      as confirmed by mass spectrometry. As expected, a higher amount of TvCP4 was
      detected in cytoplasmic vesicles, lysosomes, and on the surface of iron-rich
      parasites when compared with normal and iron-depleted parasites. The alpha-TvCP4r
      antibody protected human erythrocytes from trichomonal lysis. Additionally, TvCP4
      is expressed during infection and is part of the released products detected in
      vaginal fluids of patients with trichomonosis. Thus, data show that TvCP4 is an
      iron-induced CP that participates in T. vaginalis haemolysis. 

PMID- 24076366
TI  - A new class of aggregation inhibitor of amyloid-beta peptide based on an O-acyl
      isopeptide.
AB  - Inhibition of amyloid beta peptide (Abeta) aggregation is a potential therapeutic
      approach to treat Alzheimer's disease. We report that an O-acyl isopeptide of
      Abeta1-42 (1) containing an ester bond at the Gly(25)-Ser(26) moiety inhibits
      Abeta1-42 fibril formation at equimolar ratio. Inhibitory activity was retained
      by an N-Me-beta-Ala(26) derivative (2), in which the ester of 1 was replaced with
      N-methyl amide to improve chemical stability at physiological pH. Inhibition was
      verified by fluorescence anisotropy, Western blot, and atomic force microscopy.
      This report suggests a new class of Abeta aggregation inhibitor based on
      modification of Abeta1-42 at Gly(25)-Ser(26). 

PMID- 24076367
TI  - Effects of long-acting bronchodilators and prednisolone on inspiratory lung
      function parameters in stable COPD.
AB  - BACKGROUND: In chronic obstructive pulmonary disease (COPD), there is a poor
      correlation between forced expiratory volume in 1 s (FEV1) and dyspnea following
      bronchodilator use. Better correlations have been observed between inspiratory
      lung function parameters (ILPs) and dyspnea, which drives our interest in ILPs.
      However, the acute and prolonged effects of long-acting bronchodilators and oral
      corticosteroids on ILPs have not been well investigated. Therefore, the aim of
      this study was to investigate the effects of these treatments on the ILPs, FEV1,
      dyspnea (visual analog scale (VAS)) and clinical COPD questionnaire (CCQ).
      METHODS: Twenty-eight stable COPD patients had their ILPs and FEV1 measured both
      before and 2 h after the use of a single dose of 18 mcg bronchodilator tiotropium
      and 50 mcg salmeterol. Thereafter, the patients were randomized to 2 weeks of
      treatment with 30 mg oral prednisolone once daily or oral placebo in combination
      with daily treatment with these two bronchodilators. Four weeks after the
      cessation of the randomized treatment, the ILPs and FEV1 were again measured.
      After each intervention, any change in the VAS score was assessed. RESULTS: With
      both bronchodilators, significant improvements in ILPs were demonstrated (p <
      0.005), with the exception of changes in ILPs inspiratory capacity (IC) and
      forced inspiratory flow at 50% of the vital capacity (FIF50) after tiotropium
      inhalation. After 2 weeks of treatment with prednisolone, significant differences
      were found for ILP forced inspiratory volume in 1 s (FIV1) and FEV1 compared with
      placebo. These differences were no longer present 4 weeks after the cessation of
      prednisolone. Significant relationships between ILPs and VAS scores were only
      found after 2 weeks of treatment with prednisolone or placebo. CONCLUSIONS: After
      a single dose of long-acting bronchodilator salmeterol, significant improvements
      are observed in all ILPs and in FIV1 and PIF after tiotropium. Two weeks of oral
      corticosteroid treatment improved the FIV1 and FEV1. The dyspnea VAS score was
      only significantly correlated with the ILPs after 2 weeks of oral corticosteroid
      treatment.

PMID- 24076368
TI  - Effectiveness and safety of macrolides in bronchiectasis patients: a meta
      analysis and systematic review.
AB  - PURPOSE: Macrolides has been studied as a potential therapeutic anti-inflammatory
      agent for bronchiectasis patients, which has used as an immunoregulation agent.
      However, the efficacy and safety results of macrolides across available
      randomized controlled trials (RCTs) are controversial. The aim of this systematic
      review is to evaluate the efficacy and safety of macrolides in bronchiectasis.
      METHODS: RCTs of macrolides treatment for the patients of bronchiectasis
      published in PubMed and Cochrane Library were searched. Two authors independently
      extracted data and assessment the methodological quality. The primary efficacy
      outcome was the impact on the number of pulmonary exacerbation. Safety outcomes
      included adverse events and mortality. RESULTS: Seven RCTs were found in the
      systematic review and six studies were included in the present meta-analysis.
      Macrolides treatment showed a significant reduced rate of pulmonary exacerbation
      (RR = 0.55, 95%CI = 0.43-0.70) compared with control groups. However, subgroup
      analysis failed to find any significant changes in total 46 patients (RR = 0.20,
      95%CI = 0.03-1.58) for treatment not more than 3 months. The incidence rates of
      total adverse events showed no significant difference among the macrolides group
      and control groups. CONCLUSIONS: Long-term treatment of bronchiectasis with
      macrolides can reduce incidence of pulmonary exacerbation, especially in the
      subgroup treatment 6 months or more. There was no evidence of increased adverse
      events with macrolides. However, to verify the best macrolides regimen, more
      studies based on larger sample size and stratified by ethnicity are still needed.
      CHEMICAL COMPOUNDS STUDIED IN THIS ARTICLE: Erythromycin (PubChem CID 12560);
      Azithromycin (PubChem CID: 447043); Clarithromycin (PubChem CID: 84029);
      Roxithromycin (PubChem CID: 5480431).

PMID- 24076369
TI  - Determining the difficulty of Word Sense Disambiguation.
AB  - Automatic processing of biomedical documents is made difficult by the fact that
      many of the terms they contain are ambiguous. Word Sense Disambiguation (WSD)
      systems attempt to resolve these ambiguities and identify the correct meaning.
      However, the published literature on WSD systems for biomedical documents report
      considerable differences in performance for different terms. The development of
      WSD systems is often expensive with respect to acquiring the necessary training
      data. It would therefore be useful to be able to predict in advance which terms
      WSD systems are likely to perform well or badly on. This paper explores various
      methods for estimating the performance of WSD systems on a wide range of
      ambiguous biomedical terms (including ambiguous words/phrases and abbreviations).
      The methods include both supervised and unsupervised approaches. The supervised
      approaches make use of information from labeled training data while the
      unsupervised ones rely on the UMLS Metathesaurus. The approaches are evaluated by
      comparing their predictions about how difficult disambiguation will be for
      ambiguous terms against the output of two WSD systems. We find the supervised
      methods are the best predictors of WSD difficulty, but are limited by their
      dependence on labeled training data. The unsupervised methods all perform well in
      some situations and can be applied more widely. 

PMID- 24076370
TI  - Taishan Pinus massoniana pollen polysaccharides promote immune responses of
      recombinant Bordetella avium ompA in BALB/c mice.
AB  - To study the effects of Taishan Pinus massoniana pollen polysaccharides (TPPPS)
      on Bordetella avium outer membrane protein A (ompA) recombinant protein vaccine,
      ompA was expressed, confirmed by Western blotting and mixed with TPPPS. Female
      BALB/c mice were randomly divided into six groups (I-VI). Groups I, II, and III
      were treated with TPPPS-ompA at doses of 200, 400, and 800 mg/ml, respectively.
      Groups IV, V, and VI were treated with Freund's adjuvant-ompA, pure ompA, and
      physiological saline, respectively. On days 3, 7, 14, 21, 28, 35, 42, and 49
      after the first vaccination, antibody titers, interleukin-2 (IL-2) levels,
      peripheral blood CD4+ and CD8+ levels, and T lymphocyte proliferation rates in
      peripheral blood, as well as secreting-type immunoglobulin A (SIgA) levels in the
      duodenum, were measured. The antibody titers against ompA, IL-2, T lymphocyte
      proliferation rate, CD4+, and CD8+ in Group II were significantly (P<0.05) higher
      than those in other groups. However, little difference in SIgA content was
      observed among Groups I, II, and IV. These results indicated that TPPPS
      strengthened humoral and cellular immune response against recombinant ompA
      vaccine and 400 mg/ml TPPPS showed significance (P<0.05) compared with Freund's
      adjuvant. Therefore, TPPPS can be developed into an adjuvant for recombinant
      protein vaccines or plant-derived medicine for animal husbandry.

PMID- 24076371
TI  - Quercetin inhibits lipopolysaccharide-induced nitric oxide production in BV2
      microglial cells by suppressing the NF-kappaB pathway and activating the Nrf2
      dependent HO-1 pathway.
AB  - Abnormal nitrosative stress-induced neuroinflammation is implicated in the
      pathogenesis of neurodegenerative diseases. Therefore, it has been thought that
      nitric oxide (NO) production is a good therapeutic target. In this sense,
      quercetin is a good chemopreventive component, because it has free radical
      scavenging and anti-inflammatory activities. However, explicit mechanisms are not
      clear in the lipopolysaccharide (LPS)-stimulated BV2 microglial cell line. Here,
      we found that quercetin significantly suppressed LPS-induced NO production and
      inducible NO synthase (iNOS) expression. Notably, quercetin inhibited nuclear
      factor-kappaB (NF-kappaB) activation by inhibiting degradation of the inhibitor
      of kappa Balpha (IkappaBalpha) in LPS-stimulated BV2 microglial cells
      corresponding to the inhibitory effect of specific NF-kappaB inhibitors, namely
      proteasome inhibitor I (PSI) and MG132. Quercetin caused significant increases in
      the levels of heme oxgenase-1 (HO-1) mRNA and protein. Notably, treatment with an
      HO-1 inducer, cobalt protoporphyrin (CoPP), significantly diminished LPS
      stimulated NO production. Additionally, quercetin induced the specific DNA
      binding activity of nuclear factor-2-erythroid 2-related factor 2 (Nrf2), and
      siRNA-mediated knockdown of Nrf2 expression reduced the inhibitory effect of
      quercetin on LPS-stimulated NO production by inhibiting HO-1 expression,
      indicating that quercetin regulated NO production by inducing Nrf2-mediated HO-1
      expression. Therefore, quercetin has the potential to decrease nitrosative stress
      by suppressing NF-kappaB activation and inducing Nrf2-mediated HO-1 expression. 

PMID- 24076372
TI  - p53 Suppresses E2F1-dependent PLK1 expression upon DNA damage by forming p53-E2F1
      DNA complex.
AB  - E2F1 is implicated in transcriptional activation of polo-like kinase-1 (PLK1),
      but yet the mechanism is not fully understood. PLK1 suppression plays an
      important checkpoint role in response to DNA damage. Suppression of the PLK1 gene
      by binding of p53 to upstream p53RE2 element in the promoter has been recently
      revealed. Here we report another mechanism, in which p53 interacts with E2F1 to
      form p53-E2F1-DNA complex repressing E2F1-dependent PLK1 expression. PLK1 was
      downregulated in cisplatin exposed HCT116p53(+/+) but not HCT116p53(-/-) cells,
      indicating p53-suppressed PLK1 upon DNA damage. Co-transfection and reporter
      enzyme assays revealed that p53 suppressed but E2F1 promoted PLK1 gene
      activation. 5'-Deletion and substitution mutations showed multiple positive cis
      elements residing in the PLK1 promoter, of which at least two E2F1 sites at
      positions -75/-68 and -40/-32 were required for the full activity of the
      promoter. Combination of 5'-deletion and substitution mutations with over
      expression of p53 showed that suppression of the PLK1 gene by p53 was E2F1
      dependent: mutation of the E2F1 site at position -75/-68 partially abrogated
      suppression activity of p53; mutation of E2F1 site at position -40/-32 released
      from p53 suppression of PLK1 gene completely. Co-immunoprecipitation and
      electrophoretic mobility shift assay showed that DNA damage promoted p53-E2F1
      interaction, thereby creating a p53-E2F1 complex assembly on the PLK1 promoter in
      vitro. The in vivo formation of p53-E2F1-PLK1 promoter complex upon DNA damage
      was further evidenced by chromatin immunoprecipitation (ChIP) and re-ChIP. In
      addition, we showed that suppression of PLK1 by p53 promoted apoptosis. Our data
      suggest that p53 may interact with E2F1 to form p53-E2F1-DNA complex suppressing
      E2F1-dependent PLK1 expression. The model of p53 action on E2F1-activated PLK1
      gene may explain at least partly how p53 as a suppressor regulates the downstream
      effects of E2F1 in cellular stresses including DNA damage stress. 

PMID- 24076373
TI  - Late-assembly of human ribosomal protein S20 in the cytoplasm is essential for
      the functioning of the small subunit ribosome.
AB  - Using immuno-fluorescent probing and Western blotting analysis, we reveal the
      exclusive cytoplasm nature of the small subunit ribosomal protein S20. To
      illustrate the importance of the cellular compartmentation of S20 to the function
      of small subunit 40S, we created a nuclear resident S20NLS mutant gene and
      examined polysome profile of cells that had been transfected with the S20NLS
      gene. As a result, we observed the formation of recombinant 40S carried S20NLS
      but this recombinant 40S was never found in the polysome, suggesting such a
      recombinant 40S was translation incompetent. Moreover, by the tactic of the
      energy depletion and restoration, we were able to restrain the nuclear-resided
      S20NLS in the cytoplasm. Yet, along a progressive energy restoration, we observed
      the presence of recombinant 40S subunits carrying the S20NLS in the polysome.
      This proves that S20 needs to be cytoplasmic in order to make a functional 40S
      subunit. Furthermore, it also implies that the assembly order of ribosomal
      protein in eukaryote is orderly regulated. 

PMID- 24076374
TI  - Musashi2 modulates K562 leukemic cell proliferation and apoptosis involving the
      MAPK pathway.
AB  - The RNA-binding protein Musashi2 (Msi2) has been identified as a master regulator
      within a variety of stem cell populations via the regulation of translational
      gene expression. A recent study has suggested that Msi2 is strongly expressed in
      leukemic cells of acute myeloid leukemia patients, and elevated Msi2 is
      associated with poor prognosis. However, the potential role of Msi2 in
      leukemogenesis is still not well understood. Here, we investigated the effect of
      Msi2 knockdown on the biological properties of leukemic cells. High expression of
      Msi2 was found in K562 and KG-1a leukemic cell lines, and low expression was
      observed in the U937 cell line. We transduced K562 cells with two independent
      adenoviral shRNA vectors targeting Msi2 and confirmed knockdown of Msi2 at the
      mRNA and protein levels. Msi2 silencing inhibited cell growth and caused cell
      cycle arrest by increasing the expression of p21 and decreasing the expression of
      cyclin D1 and cdk2. In addition, knockdown of Msi2 promoted cellular apoptosis
      via the upregulation of Bax and downregulation of Bcl-2 expression. Furthermore,
      Msi2 knockdown resulted in the inactivation of the ERK/MAPK and p38/MAPK
      pathways, but no remarkable change in p-AKT was observed. These data provide
      evidence that Msi2 plays an important role in leukemogenesis involving the MAPK
      signaling pathway, which indicates that Msi2 may be a novel target for leukemia
      treatment.

PMID- 24076376
TI  - Spatial attention: differential shifts in pseudoneglect direction with time-on
      task and initial bias support the idea of observer subtypes.
AB  - Asymmetry in human spatial attention has long been documented. In the general
      population the majority of individuals tend to misbisect horizontal lines to the
      left of veridical centre. Nonetheless in virtually all previously reported
      studies on healthy participants, there have been subsets of people displaying
      rightward biases. In this study, we report differential time-on task effects
      depending on participants' initial pseudoneglect bias: participants with an
      initial left bias in a landmark task (in which they had to judge whether a
      transection mark appeared closer to the right or left end of a line) showed a
      significant rightward shift over the course of the experimental session, whereas
      participants with an initial right bias shifted leftwards. We argue that these
      differences in initial biases as well as the differential shifts with time-on
      task reflect genuine observer subtypes displaying diverging behavioural patterns.
      These observer subtypes could be driven by differences in brain organisation
      and/or lateralisation such as varying anatomical pathway asymmetries (Thiebaut de
      Schotten et al., 2011). 

PMID- 24076375
TI  - Child abuse is related to inflammation in mid-life women: role of obesity.
AB  - OBJECTIVE: Elevated inflammation biomarkers are associated with incident
      cardiovascular disease. Several studies suggest that childhood abuse may be
      associated with inflammation later in life. This study examined whether childhood
      abuse predicted elevated levels of C-reactive protein (CRP) and whether the
      association was due to body size. METHODS: Participants were 326 (104 Black, 222
      White) women from the Pittsburgh site of the Study of Women's Health Across the
      Nation (SWAN). SWAN included a baseline assessment of pre-menopausal or early
      peri-menopausal women in mid-life (mean age=45.7), and CRP, depressive symptoms,
      body mass index (BMI), and other covariates were measured over 7 annual follow-up
      visits. The Childhood Trauma Questionnaire, a standardized measure that
      retrospectively assesses abuse and neglect in childhood and adolescence, was
      administered at year 8 or 9 of follow-up. RESULTS: Approximately 37% of the
      participants reported a history of abuse or neglect. Generalized estimating
      equations showed that sexual and emotional abuse, emotional and physical neglect,
      and the total number of types of abuse were associated with higher CRP levels
      over 7 years, adjusting for race, age, education, smoking status, use of hormone
      therapy, depressive symptoms, occurrence of heart attack or stroke, and
      medications for hypertension. The coefficients for indirect effects for emotional
      and sexual abuse, physical neglect, and total number of types of abuse on CRP
      levels through BMI were significant. A history of emotional abuse and neglect was
      related to percent change in CRP over the 7 years but not through percent change
      in BMI over the 7 years. CONCLUSION: A history of childhood abuse and neglect
      retrospectively reported is related to overall elevated inflammation in mid-life
      women, perhaps through obesity. A history of some types of abuse and neglect
      (emotional) may be related to change in inflammation, independent of
      simultaneously measured change in BMI.

PMID- 24076377
TI  - Re: Bhageria A, Nayak B, Seth A, Dogra PN, Kumar R. Pediatric percutaneous
      nephrolithotomy: Single-centre 10-year experience. J Pediatr Urol 2013;9:472-5.

PMID- 24076378
TI  - Response to "Reputation rankings for pediatric urology moderately".

PMID- 24076379
TI  - Assessment of small fiber neuropathy to predict future risk of type 2 diabetes.
AB  - OBJECTIVE: Sudomotor dysfunction due to small fiber neuropathy can be observed
      very early in pre-diabetes. The aim of this study was to assess the predictive
      power of EZSCAN, a non invasive, quick and simple measurement of sudomotor
      function to identify glucose impairment. RESEARCH DESIGN AND METHODS: The study
      was performed in 76 German subjects at risk of diabetes. Glucose metabolism was
      assessed by using, oral glucose tolerance test (OGTT) at baseline and after 2
      year follow-up. Sudomotor function was evaluated by measuring hand and foot
      electrochemical sweat conductances to calculate a risk score. RESULTS: At
      baseline, 38 patients had normal glucose tolerance (NGT), 34 had pre-diabetes
      (impaired fasting glucose, IFG and/or impaired glucose tolerance, IGT) and 4 had
      newly diagnosed type 2 diabetes. The AUC values for FPG, 2h-OGTT glucose, 1h-OGTT
      glucose, HbA1C and EZSCAN score to predict pre-diabetes were 0.50, 0.65, 0.64,
      0.72 and 0.76, respectively. Subjects having a moderate or high EZSCAN score
      (>50) at baseline had a substantially increased risk for having IFG and/or IGT at
      follow-up visit presented by an odds ratio of 12.0 [1.4-100.5], the OR for having
      1h-OGTT >= 8.6mmol/L at follow-up was 9.8 [1.0-92.8] and for having HbA1C >= 5.7%
      was 15.7 [1.9-131.5] compared to subjects with low EZSCAN risk. CONCLUSIONS: This
      preliminary study, which must be confirmed in a larger population, shows that
      EZSCAN risk score is associated with diabetes progression which have implications
      for prevention and disease management.

PMID- 24076380
TI  - Five novel naphthylisoquinoline alkaloids with growth inhibitory activities
      against human leukemia cells HL-60, K562 and U937 from stems and leaves of
      Ancistrocladus tectorius.
AB  - Two new 7,6'-coupled naphthylisoquinolines, namely ancistrotectorines A (1) and B
      (2), two new 5,3'-coupled naphthylisoquinolines, namely ancistrotectorines C (3)
      and D (4), and one new 7,8-coupled naphthylisoquinoline, namely ancistrotectorine
      E (5), together with 9 known naphthylisoquinoline alkaloids, hamatine (6),
      ancistrobertsonine B (7), ancistrocladinine (8), hamatinine (9),
      ancistrotanzanine A (10), ancistrotanzanine B (11), ancistrotectoriline B (12), 7
      epi-ancistrobrevine D (13), and ancistrotectorine (14), were isolated from the
      70% EtOH extract of Ancistrocladus tectorius. Their structures were elucidated
      based on the extensive analysis of spectroscopic data (1D, 2D NMR and MS).
      Compound 5 exhibited inhibitory activities against HL-60, K562 and U937 cell
      lines with IC50 values of 1.70, 4.18 and 2.56 MUM respectively.

PMID- 24076381
TI  - Numerical approximation abilities correlate with and predict informal but not
      formal mathematics abilities.
AB  - Previous research has found a relationship between individual differences in
      children's precision when nonverbally approximating quantities and their school
      mathematics performance. School mathematics performance emerges from both
      informal (e.g., counting) and formal (e.g., knowledge of mathematics facts)
      abilities. It remains unknown whether approximation precision relates to both of
      these types of mathematics abilities. In the current study, we assessed the
      precision of numerical approximation in 85 3- to 7-year-old children four times
      over a span of 2years. In addition, at the final time point, we tested children's
      informal and formal mathematics abilities using the Test of Early Mathematics
      Ability (TEMA-3). We found that children's numerical approximation precision
      correlated with and predicted their informal, but not formal, mathematics
      abilities when controlling for age and IQ. These results add to our growing
      understanding of the relationship between an unlearned nonsymbolic system of
      quantity representation and the system of mathematics reasoning that children
      come to master through instruction. 

PMID- 24076382
TI  - Emergent self-regulation skills among very young ethnic minority children: a
      confirmatory factor model.
AB  - Emerging self-regulation skills were assessed in 407 low-income African American
      and Latino (primarily Mexican-origin) preschoolers. A battery of self-regulation
      tasks was administered when children were 21/2 years old and again approximately
      1 year later. Confirmatory factor analyses supported four components of self
      regulation: inhibitory control, complex response inhibition, set shifting, and
      working memory. Complex response inhibition was too rare a skill in this sample
      to be detected reliably from measures collected at 21/2 years of age, but it
      emerged from measures collected at 31/2 years. In addition, significant ethnic
      differences were found in that African American children scored better on
      measures of complex response inhibition and set shifting, whereas Latino children
      scored better on measures of inhibitory control and working memory. Implications
      of study findings for measuring self-regulation in low-income ethnic diverse
      populations of young children, as well as for developing interventions to enhance
      self-regulation development, are discussed. 

PMID- 24076383
TI  - Attending to what matters: flexibility in adults' and infants' action perception.
AB  - Action perception is selective in that observers attend to and encode certain
      dimensions of action over others. But how flexible is action perception in its
      selection of perceptual information? One possibility is that observers
      consistently attend to particular dimensions of action over others across
      different contexts. Another possibility, tested here, is that observers flexibly
      vary their attention to different dimensions of action based on the context in
      which action occurs. We investigated 9.5-month-old infants' and adults' ability
      to attend to drop height under varying contexts-aiming to drop an object into a
      narrow container versus a wide container. We predicted differential attention to
      increases in aiming height for the narrow container versus the wide container
      because an increase in aiming height has a differential effect on success (i.e.,
      getting the object into the container) depending on the width of the container.
      Both adults and infants showed an asymmetry in their attention to aiming height
      as a function of context; in the wide container condition increases and decreases
      in aiming height were equally detectable, whereas in the narrow container
      condition observers more readily discriminated increases over decreases in aiming
      height. These results indicate that action perception is both selective and
      flexible according to context, aiding in action prediction and infants' social
      cognitive development more broadly. 

PMID- 24076384
TI  - Limited impairments of associative learning in a mouse model of accelerated
      senescence.
AB  - Research concerning impairment of associative learning during aging remains
      limited. The senescence-accelerated mice (SAM) prone/8 (P8) has been proposed as
      a useful model for the study of aging, and SAM resistant/1(SAMR1) is its control
      as a normal aging strain. Classical eyeblink conditioning has long been served as
      a model of associative learning. In order to explore the effects of aging on
      associative learning in SAM, the present study successively tested three
      paradigms of eyeblink conditioning in SAMP8 and SAMR1: classical single cue trace
      eyeblink conditioning (TEC), discriminative trace eyeblink conditioning and
      reversal learning of TEC. Behavioral performance indicated that SAMP8 could
      acquire limited single-cue trace eyeblink conditioning task and two-tone
      discrimination trace eyeblink conditioning with a relative lower acquisition rate
      compared to SAMR1. Both SAMP8 and SAMR1 failed to acquire reversal learning of
      discriminative TEC, and SAMP8' startle reflex to tone CS was lower than SAMR1.
      These results indicated that the impairments of aging on associative learning
      were incomplete in SAMP8. 

PMID- 24076385
TI  - Selection for low mortality in laying hens affects catecholamine levels in the
      arcopallium, a brain area involved in fear and motor regulation.
AB  - Feather pecking (FP) in laying hens may cause mortality due to cannibalism. Novel
      breeding methods using survival days of group-housed siblings allow for the
      genetic selection of laying hens with low mortality (LML: low mortality line) due
      to cannibalism. Previous studies have demonstrated less fear-related behavior and
      also less FP in LML hens compared to CL. Selection also caused changes in
      locomotor behavior in an open field. It is unknown, however, whether selection
      for low mortality affects central neurotransmitter levels. In this study, brain
      monoamine levels were measured in the dorsal thalamus, medial striatum,
      hippocampus and arcopallium of adult laying hens of both LML and CL using HPLC.
      Brain samples were collected after 5-min of manual restraint. The most prominent
      line differences were found in the arcopallium. Compared to CL, LML had lower
      levels of noradrenaline (NA) and 3,4-dihydroxyphenylacetic acid (DOPAC) and
      tended to have lower levels of dopamine (DA), homovanillic acid (HVA), and 5
      hydroxyindoleacetic acid (5-HIAA). Levels of serotonin (5-HT), 5-HT- and DA
      turnover in this brain area were not affected by line. LML showed less fear
      related behavior during the restraint than CL. These findings show that selection
      for low mortality in hens leads to changes of predominantly the dopaminergic
      system in the chicken's arcopallium, a forebrain somatomotor area also related to
      fear. This suggests a relationship between catecholamine functioning in this
      brain area and FP and cannibalistic behavior in chickens and underpins previously
      found relationships between FP, fear and high activity.

PMID- 24076386
TI  - Proposed docking interface between peptidoglycan and the target recognition
      domain of zoocin A.
AB  - A docking model is proposed for the target recognition domain of the lytic
      exoenzyme zoocin A with the peptidoglycan on the outer cell surface of sensitive
      bacterial strains. Solubilized fragments from such peptidoglycans perturb
      specific backbone and side chain amide resonances in the recombinant form of the
      domain designated rTRD as detected in two-dimensional (1)H-(15)N correlation NMR
      spectra. The affected residues comprise a shallow surface cleft on the protein
      surface near W115, N53, N117, and Q105 among others, which interacts with the
      peptide portion of the peptidoglycan. Calculations with AutoDock Vina provide
      models of the docking interface. There is approximate homology between the rTDR
      peptidoglycan docking site and the antigen binding site of Fab antibodies with
      the immunoglobin fold. EDTA was also found to bind to rTRD, but at a site
      distinct from the proposed peptidoglycan docking site. 

PMID- 24076387
TI  - Lentiviral-mediated transfer of CDNF promotes nerve regeneration and functional
      recovery after sciatic nerve injury in adult rats.
AB  - Peripheral nerve injury is often followed by incomplete and unsatisfactory
      functional recovery and may be associated with sensory and motor impairment of
      the affected limb. Therefore, a novel method is needed to improve the speed of
      recovery and the final functional outcome after peripheral nerve injuries. This
      report investigates the effect of lentiviral-mediated transfer of conserved
      dopamine neurotrophic factor (CDNF) on regeneration of the rat peripheral nerve
      in a transection model in vivo. We observed notable overexpression of CDNF
      protein in the distal sciatic nerve after recombinant CDNF lentiviral vector
      application. We evaluated sciatic nerve regeneration after surgery using light
      and electron microscopy and the functional recovery using the sciatic functional
      index and target muscle weight. HE staining revealed better ordered structured in
      the CDNF-treated group at 8 weeks post-surgery. Quantitative analysis of
      immunohistochemistry of NF200 and S-100 in the CDNF group revealed significant
      improvement of axonal and Schwann cell regeneration compared with the control
      groups at 4 weeks and 8 weeks after injury. The thickness of the myelination
      around the axons in the CDNF group was significantly higher than in the control
      groups at 8 weeks post-surgery. The CDNF group displayed higher muscle weights
      and significantly increased sciatic nerve index values. Our findings suggest that
      CDNF gene therapy could provide durable and stable CDNF protein concentration and
      has the potential to enhance peripheral nerve regeneration, morphological and
      functional recovery following nerve injury, which suggests a promising strategy
      for peripheral nerve repair.

PMID- 24076388
TI  - Ran GTPase protein promotes human pancreatic cancer proliferation by deregulating
      the expression of Survivin and cell cycle proteins.
AB  - Ran, a member of the Ras GTPase family, has important roles in nucleocytoplasmic
      transport. Herein, we detected Ran expression in pancreatic cancer and explored
      its potential role on tumour progression. Overexpressed Ran in pancreatic cancer
      tissues was found highly correlated with the histological grade. Downregulation
      of Ran led to significant suppression of cell proliferation, cell cycle arrest at
      the G1/S phase and induction of apoptosis. In vivo studies also validated that
      result. Further studies revealed that those effects were at least partly mediated
      by the downregulation of Cyclin A, Cyclin D1, Cyclin E, CDK2, CDK4, phospho-Rb
      and Survivin proteins and up regulation of cleaved Caspase-3.

PMID- 24076389
TI  - Highly purified, multi-wall carbon nanotubes induce light-chain 3B expression in
      human lung cells.
AB  - Bronchial epithelial cells are targets of inhalation and play a critical role in
      the maintenance of mucosal integrity as mechanical barriers against various
      particles. Our previous result suggest that vapor-grown carbon fiber, HTT2800,
      which is one of the most highly purified multi-wall carbon nanotubes (MWCNT)
      showed cellular uptake of the carbon nanotube, increased cell death, enhanced DNA
      damage, and induced cytokine release. Increasing evidence suggests that autophagy
      may critically influence vital cellular processes such as apoptosis, cell
      proliferation and inflammation and thereby may play a critical role in pulmonary
      diseases. Autophagy was recently recognized as a critical cell death pathway, and
      autophagosome accumulation has been found to be associated with the exposure of
      various nanoparticles. In this study, the authors focus on the autophagic
      responses of HTT2800 exposure. The HTT2800-exposed cells induced LC3B expression
      and induced cell growth inhibition.

PMID- 24076390
TI  - Direct inhibition of cell surface ephrin-B2 by recombinant ephrin-B2/FC.
AB  - First messengers and viral transfection are the two most common ways to stimulate
      cells for signal output, although their applications are limited. We investigated
      mechanisms of inducing neural stem cell differentiation using recombinant ephrin
      B2/Fc and found that it acted as a ligand and inhibited endogenous ephrin-B2,
      which maintenance of the neural progenitor cell state, by direct interference.
      Our results showed the movement of ephrin-B2/Fc within the cell and indicated
      that it recycled to the plasma membrane surface, revealing a possible pattern of
      ephrin trafficking. Our results also serve as proof of concept for the
      reconstruction of the intracellular domain of ephrin using an artificial receptor
      to direct input signals in future studies.

PMID- 24076391
TI  - The Reelin receptors ApoER2 and VLDLR are direct target genes of HIC1
      (Hypermethylated In Cancer 1).
AB  - The tumor suppressor gene HIC1 (Hypermethylated In Cancer 1) is located in
      17p13.3 a region frequently hypermethylated or deleted in tumors and in a
      contiguous-gene syndrome, the Miller-Dieker syndrome which includes classical
      lissencephaly (smooth brain) and severe developmental defects. HIC1 encodes a
      transcriptional repressor involved in the regulation of growth control, DNA
      damage response and cell migration properties. We previously demonstrated that
      the membrane-associated G-protein-coupled receptors CXCR7, ADRB2 and the tyrosine
      kinase receptor EphA2 are direct target genes of HIC1. Here we show that ectopic
      expression of HIC1 in U2OS and MDA-MB-231 cell lines decreases expression of the
      ApoER2 and VLDLR genes, encoding two canonical tyrosine kinase receptors for
      Reelin. Conversely, knock-down of endogenous HIC1 in BJ-Tert normal human
      fibroblasts through RNA interference results in the up-regulation of these two
      Reelin receptors. Finally, through chromatin immunoprecipitation (ChIP) in BJ
      Tert fibroblasts, we demonstrate that HIC1 is a direct transcriptional repressor
      of ApoER2 and VLDLR. These data provide evidence that HIC1 is a new regulator of
      the Reelin pathway which is essential for the proper migration of neuronal
      precursors during the normal development of the cerebral cortex, of Purkinje
      cells in the cerebellum and of mammary epithelial cells. Deregulation of this
      pathway through HIC1 inactivation or deletion may contribute to its role in tumor
      promotion. Moreover, HIC1, through the direct transcriptional repression of ATOH1
      and the Reelin receptors ApoER2 and VLDLR, could play an essential role in normal
      cerebellar development. 

PMID- 24076392
TI  - TNF receptor 2 protects oligodendrocyte progenitor cells against oxidative
      stress.
AB  - The neuroprotective role of TNF receptor 2 (TNFR2) has been shown in various
      studies. However, a direct role of TNFR2 in oligodendrocyte function has not yet
      been demonstrated. Using primary oligodendrocytes of transgenic mice expressing
      human TNFR2, we show here that TNFR2 is primarily expressed on oligodendrocyte
      progenitor cells. Interestingly, preconditioning with a TNFR2 agonist protects
      these cells from oxidative stress, presumably by increasing the gene expression
      of distinct anti-apoptotic and detoxifying proteins, thereby providing a
      potential mechanism for the neuroprotective role of TNFR2 in oligodendrocyte
      progenitor cells.

PMID- 24076393
TI  - The flavonoid myricetin reduces nocturnal melatonin levels in the blood through
      the inhibition of serotonin N-acetyltransferase.
AB  - Melatonin is secreted during the hours of darkness and is thought to influence
      the circadian and seasonal timing of a variety of physiological processes. AANAT,
      which is expressed in the pineal gland, retina, and various other tissues,
      catalyzes the conversion of serotonin to N-acetylserotonin and is the rate
      limiting enzyme in the biosynthetic pathway of melatonin. The compounds that
      modulate the activity of AANAT can be used to treat patients with circadian
      rhythm disorders that are associated with specific circadian rhythm alterations,
      such as shift work disorder. In the present study, we screened modulators of
      AANAT activity from the water extracts of medicinal plants. Among the 267 tested
      medicinal plant extracts, Myricae Cortex (Myrica rubra), Perillae Herba (Perilla
      sikokiana), and Eriobotryae Folium (Eriobotrya japonica) showed potent inhibition
      of AANAT activity. Myricetin (5,7,3',4',5'-pentahydroxyflavonol), a main
      component of the Myricae Cortex, strongly inhibited the activity of AANAT and
      probably block the access to the substrate by docking to the catalytic residues
      that are important for AANAT activity. Myricetin significantly decreased the
      nocturnal serum melatonin levels in rats. In addition, the locomotor activity of
      rats treated with myricetin decreased during the nighttime and slightly increased
      throughout the day. These results suggest that myricetin could be used as a
      therapy to increase nighttime alertness by changing the circadian rhythm of serum
      melatonin and locomotor activity.

PMID- 24076395
TI  - Skin penetration of topically applied white mustard extract and its effects on
      epidermal Langerhans cells and cytokines.
AB  - White mustard (Sinapis alba L.), a traditional Chinese medicine, is widely used
      in China for clinical prevention and treatment of the common winter diseases of
      asthma and bronchitis by percutaneous administration in the summer. The present
      study is to investigate the skin penetration behavior of white mustard extract to
      elucidate the possible mechanism underlying its immune regulation activity. The
      principle active compound of the extract, sinapine thiocyanate (ST), was used as
      a marker. The skin penetration of ST in white mustard extract was examined in
      vitro and in vivo. In vitro study on excised guinea pig hairless skin using Franz
      diffusion cell revealed ST can permeate through the skin and also accumulate in
      the skin. In vivo study was carried out on the guinea pig hairless skin for 24 h,
      and then skin was excised for frozen section, ST from the sections were extracted
      to quantify the amount of drug in different skin layers. The detailed
      distribution of ST showed that it accumulated in the epidermis, especially in the
      stratum corneum. After treatment with white mustard extract for 24h, the skin was
      stained with ATPase, and the morphometric parameters of epidermal LCs were
      compared to the untreated control through image-analysis system. A statistically
      significant reduction in LC density and increase in shape factor were observed.
      Cytokines related to LCs migration including interleukin 1beta (IL-1beta) and
      tumor necrosis factor alpha (TNF-alpha) were also measured after white mustard
      extract treated at different time points. Compared to the untreated group, white
      mustard extract significantly enhanced the release of IL-1beta and TNFalpha. The
      morphometric changes of LCs and the local cytokine release after topical white
      mustard treatment may explain the activity of the white mustard extract against
      asthma and bronchitis.

PMID- 24076394
TI  - Structural and functional plasticity in long-term cultures of adult ventricular
      myocytes.
AB  - Cultured heart cells have long been valuable for characterizing biological
      mechanism and disease pathogenesis. However, these preparations have limitations,
      relating to immaturity in key properties like excitation-contraction coupling and
      beta-adrenergic stimulation. Progressive attenuation of the latter is intimately
      related to pathogenesis and therapy in heart failure. Highly valuable would be a
      long-term culture system that emulates the structural and functional changes that
      accompany disease and development, while concurrently permitting ready access to
      underlying molecular events. Accordingly, we here produce functional monolayers
      of adult guinea-pig ventricular myocytes (aGPVMs) that can be maintained in long
      term culture for several weeks. At baseline, these monolayers exhibit
      considerable myofibrillar organization and a significant contribution of
      sarcoplasmic reticular (SR) Ca(2+) release to global Ca(2+) transients. In terms
      of electrical signaling, these monolayers support propagated electrical activity
      and manifest monophasic restitution of action-potential duration and conduction
      velocity. Intriguingly, beta-adrenergic stimulation increases chronotropy but not
      inotropy, indicating selective maintenance of beta-adrenergic signaling. It is
      interesting that this overall phenotypic profile is not fixed, but can be readily
      enhanced by chronic electrical stimulation of cultures. This simple environmental
      cue significantly enhances myofibrillar organization as well as beta-adrenergic
      sensitivity. In particular, the chronotropic response increases, and an inotropic
      effect now emerges, mimicking a reversal of the progression seen in heart
      failure. Thus, these aGPVM monolayer cultures offer a valuable platform for
      clarifying long elusive features of beta-adrenergic signaling and its plasticity.

PMID- 24076396
TI  - Precipitation-lyophilization-homogenization (PLH) for preparation of
      clarithromycin nanocrystals: influencing factors on physicochemical properties
      and stability.
AB  - Nanocrystals is one of effective technologies used to improve solubility and
      dissolution behavior of poorly soluble drugs. Clarithromycin is classified in BCS
      class II having low bioavailability due to very low dissolution behavior. The
      main purpose of this study was to investigate an efficiency of clarithromycin
      nanocrystals preparation by precipitation-lyophilization-homogenization (PLH)
      combination method in comparison with high pressure homogenization (HPH) method.
      The factors influencing particle size reduction and physical stability were
      assessed. The results showed that the PLH technique provided an effective and
      rapid reduction of particle size of nanocrystals to 460 +/- 10 nm with
      homogeneity size distribution after only the fifth cycle of homogenization,
      whereas the same size was attained after 30 cycles by the HPH method. The
      smallest nanocrystals were achieved by using the combination of poloxamer 407
      (2%, w/v) and SLS (0.1%, w/v) as stabilizers. This combination could prevent the
      particle aggregation over 3-month storage at 4  degrees C. The results from SEM
      showed that the clarithromycin nanocrystals were in cubic-shaped similar to its
      initial particle morphology. The DSC thermogram and X-ray diffraction pattern of
      nanocrystals were not different from the original drug except for intensity of
      peaks which indicated the presenting of nanocrystals in the crystalline state
      and/or partial amorphous form. In addition, the dissolution of the clarithromycin
      nanocrystals was dramatically increased as compared to the coarse clarithromycin.

PMID- 24076397
TI  - Skin electroporation for transdermal drug delivery: the influence of the order of
      different square wave electric pulses.
AB  - Electroporation can be used as an active enhancement method for intra- and
      transdermal drug delivery. Differences in response of skin to electric pulses
      depend on their amplitude, duration and number and have been a point of interest
      in the past. While protocols consisting of the same repetitive, mostly
      exponentially decaying pulses have been used before, this study is focused on
      comparing different combinations of square wave short high voltage (HV) and
      longer low voltage (LV) electroporation pulses. Our in vitro experimental results
      show that longer LV pulses significantly increase subsequent passive transport of
      calcein through dermatomed pig skin, while short HV pulses alone result in
      negligible calcein passive transdermal transport. Surprisingly, when the long LV
      pulses are preceded by short duration HV pulses, the total calcein transported is
      reduced significantly. This result is explained using a theoretical physics based
      model of individual local transport region (LTR) evolution during the applied LV
      pulse. The theoretical model shows that HV pulses alter the structure of the
      stratum corneum in such a way that when the LV pulses are applied, insufficient
      thermal energy is generated to initiate LTR expansion. Together, the experimental
      results and theoretical predictions show that the total pulse energy alone cannot
      account for total solute transport: that the order of the types of pulses
      administered must also be considered. Our findings open a direction for further
      improvement of the method using new protocols. 

PMID- 24076398
TI  - Accelerated ketoprofen release from polymeric matrices: importance of the
      homogeneity/heterogeneity of excipient distribution.
AB  - Polymeric matrices loaded with 10-50% ketoprofen were prepared by hot-melt
      extrusion or spray-drying. Eudragit E, PVP, PVPVA and HPMC were studied as matrix
      formers. Binary "drug-Eudragit E" as well as ternary "drug-Eudragit E-PVP", "drug
      Eudragit E-PVPVA" and "drug-Eudragit E-HPMC" combinations were investigated and
      characterized by optical macro/microscopy, SEM, particle size measurements, mDSC,
      X-ray diffraction and in vitro drug release studies in 0.1 M HCl. In all cases
      ketoprofen release was much faster compared to a commercially available product
      and the dissolution of the drug powder (as received). Super-saturated solutions
      were obtained, which were stable during at least 2 h. Importantly, not only the
      composition of the systems, but also their inner structure potentially
      significantly affected the resulting ketoprofen release kinetics: For instance,
      spray-drying ternary ketoprofen:Eudragit E:HPMC combinations led to a more
      homogenous HPMC distribution within the systems than hot-melt extrusion, as
      revealed by mDSC and X-ray diffraction. This more homogenous HPMC distribution
      resulted in more pronounced hindrance for water and drug diffusion and, thus,
      slower drug release from spray-dried powder compared to hot-melt extrudates of
      identical composition. This "homogeneity/heterogeneity effect" even
      overcompensated the "system size effect": the surface exposed to the release
      medium was much larger in the case of the spray-dried powder. All formulations
      were stable during storage at ambient conditions in open vials.

PMID- 24076399
TI  - MCM-41 as a useful vector for rutin topical formulations: synthesis,
      characterization and testing.
AB  - Rutin, the glycoside of quercetin, could be used in topical preparations because
      of its antioxidant and radical scavenging properties, but its employ in cosmetic
      and pharmaceutical products is limited by poor physico-chemical stability. These
      issues were addressed by preparing, characterizing and testing rutin inclusion
      complexes with MCM-41 mesoporous silica. The effect of surface functionalization
      with aminopropyl groups (NH2-MCM-41) on the molecules properties was studied. The
      organic/inorganic interaction was confirmed by many techniques. In particular,
      the high inclusion of rutin in the pores of NH2-MCM-41 was assessed by XRD, TGA,
      gas-volumetric analysis (BET), while FTIR spectroscopy allowed to analyse with
      great detail the molecular interaction with the inorganic surface. Rutin was
      stabilized against UV degradation, mostly by its inclusion in NH2-MCM-41. Ex vivo
      studies showed a greater accumulation in porcine skin in the case of rutin
      complexed with NH2-MCM-41. Not only antioxidant properties of rutin were
      maintained after immobilization but, with aminopropyl silica, the metal-chelating
      activity increased noticeably. The immobilization of rutin in aminopropyl silica
      resulted in better performance in terms of activity and photostability,
      suggesting the importance of functionalization in stabilizing organic molecules
      within silica pores.

PMID- 24076401
TI  - IARC classes 1 and 2 carcinogens are successfully identified by an alternative
      strategy that detects DNA-reactivity and cell transformation ability of
      chemicals.
AB  - For decades, traditional toxicology has been the ultimate source of information
      on the carcinogenic potential of chemicals; however with increasing demand on
      regulation of chemicals and decreasing resources for testing, opportunities to
      accept "alternative" approaches have dramatically expanded. The need for tools
      able to identify carcinogens in shorter times and at a lower cost in terms of
      animal lives and money is still an open issue, and the present strategies and
      regulations for carcinogenicity pre-screening do not adequately protect human
      health. In previous papers, we have proposed an integrated in vitro/in silico
      strategy that detects DNA-reactivity and tissue disorganization/disruption by
      chemicals, and we have shown that the combination of Salmonella and Structural
      Alerts for the DNA-reactive carcinogens, and in vitro cell transformation assays
      for nongenotoxic carcinogens permits the identification of a very large
      proportion (up to 95%) of rodent carcinogens, while having a considerable
      specificity with the rodent noncarcinogens. In the present paper we expand the
      previous investigation and show that this alternative strategy identifies
      correctly IARC Classes 1 and 2 carcinogens. If implemented, this alternative
      strategy can contribute to improve the protection of human health while
      decreasing the use of animals. 

PMID- 24076400
TI  - [Report of the ordinary general assembly of the Morphologists' Association].

PMID- 24076402
TI  - Level of primary DNA damage in the early stage of metabolic syndrome.
AB  - Metabolic syndrome (MetS) is a multi-component disease, characterised by
      abdominal obesity, hypertension, hyperglycaemia and dyslipidaemia. Since the
      number of MetS patients has significantly increased over the past two decades and
      because MetS may lead to development of cardiovascular diseases, diabetes type-2,
      and cancer, it has become important to extend the knowledge on the pathogenesis
      of MetS and to establish its possible early biomarkers. Studies on MetS and DNA
      damage are few and are inconclusive. The aim of this study was to elucidate the
      involvement of DNA damage in the development of MetS and to establish if DNA
      damage can serve as early biomarker of MetS. A total of 121 subjects participated
      in the study: 56 healthy controls and 65 MetS patients who were diagnosed with
      MetS for the first time. The amount of primary DNA damage in peripheral
      leukocytes of the subjects was assessed with three types of comet assay: the
      alkaline, the hOGG1-modified, and the neutral comet assay. In addition, the
      extent of oxidative DNA damage was monitored in urine by assessing 8-oxo-dG. The
      parameters of the three types of comet assay did not differ between the control
      and the MetS group. Interestingly, urinary 8-oxo-dG level in the control group
      was higher than in the MetS group. Our results imply that DNA damage is not
      involved in the early stage of MetS and, therefore, DNA damage cannot serve as an
      early marker of MetS. 

PMID- 24076403
TI  - Activation of AMP-activated protein kinase revealed by hydrogen/deuterium
      exchange mass spectrometry.
AB  - AMP-activated protein kinase (AMPK) monitors cellular energy, regulates genes
      involved in ATP synthesis and consumption, and is allosterically activated by
      nucleotides and synthetic ligands. Analysis of the intact enzyme with
      hydrogen/deuterium exchange mass spectrometry reveals conformational
      perturbations of AMPK in response to binding of nucleotides, cyclodextrin, and a
      synthetic small molecule activator, A769662. Results from this analysis clearly
      show that binding of AMP leads to conformational changes primarily in the gamma
      subunit of AMPK and subtle changes in the alpha and beta subunits. In contrast,
      A769662 causes profound conformational changes in the glycogen binding module of
      the beta subunit and in the kinase domain of the alpha subunit, suggesting that
      the molecular binding site of the latter resides between the alpha and beta
      subunits. The distinct short- and long-range perturbations induced upon binding
      of AMP and A769662 suggest fundamentally different molecular mechanisms for
      activation of AMPK by these two ligands. 

PMID- 24076404
TI  - A helical RGD motif promoting cell adhesion: crystal structures of the
      Helicobacter pylori type IV secretion system pilus protein CagL.
AB  - RGD tripeptide motifs frequently mediate ligand binding to integrins. The type IV
      secretion system (T4SS) protein CagL of the gastric pathogen Helicobacter pylori
      also contains an RGD motif. CagL decorates the T4SS pilus and may function as an
      adhesin for host cells. Whether CagL binds integrins via its RGD motif is under
      debate. Here, we present crystal structures of CagL revealing an elongated four
      helix bundle that appears evolutionarily unrelated to the proposed VirB5
      orthologs. The RGD motif is surface-exposed but located within a long alpha
      helix. This is unprecedented as previously characterized integrin-binding RGD
      motifs are located within extended or flexible loops. Yet, adhesion of gastric
      epithelial cells to CagL was strictly RGD-dependent. Comparison of seven
      crystallographically independent molecules reveals substantial structural
      flexibility. Intramolecular disulfide bonds engineered to reduce CagL flexibility
      resulted in more stable protein, but unable to support cell adhesion. CagL may
      thus partly unfold during receptor binding. 

PMID- 24076405
TI  - Structural analysis of the G-box domain of the microcephaly protein CPAP suggests
      a role in centriole architecture.
AB  - Centrioles are evolutionarily conserved eukaryotic organelles composed of a
      protein scaffold surrounded by sets of microtubules organized with a 9-fold
      radial symmetry. CPAP, a centriolar protein essential for microtubule
      recruitment, features a C-terminal domain of unknown structure, the G-box. A
      missense mutation in the G-box reduces affinity for the centriolar shuttling
      protein STIL and causes primary microcephaly. Here, we characterize the molecular
      architecture of CPAP and determine the G-box structure alone and in complex with
      a STIL fragment. The G-box comprises a single elongated beta sheet capable of
      forming supramolecular assemblies. Structural and biophysical studies highlight
      the conserved nature of the CPAP-STIL complex. We propose that CPAP acts as a
      horizontal "strut" that joins the centriolar scaffold with microtubules, whereas
      G-box domains form perpendicular connections. 

PMID- 24076406
TI  - Improved crystallographic structures using extensive combinatorial refinement.
AB  - Identifying errors and alternate conformers and modeling multiple main-chain
      conformers in poorly ordered regions are overarching problems in crystallographic
      structure determination that have limited automation efforts and structure
      quality. Here, we show that implementation of a full factorial designed set of
      standard refinement approaches, termed ExCoR (Extensive Combinatorial
      Refinement), significantly improves structural models compared to the traditional
      linear tree approach, in which individual algorithms are tested linearly and are
      only incorporated if the model improves. ExCoR markedly improved maps and models
      and reveals building errors and alternate conformations that were masked by
      traditional refinement approaches. Surprisingly, an individual algorithm that
      renders a model worse in isolation could still be necessary to produce the best
      overall model, suggesting that model distortion allows escape from local minima
      of optimization target function, here shown to be a hallmark limitation of the
      traditional approach. ExCoR thus provides a simple approach to improving
      structure determination. 

PMID- 24076407
TI  - Positive emotion dysregulation across mood disorders: how amplifying versus
      dampening predicts emotional reactivity and illness course.
AB  - Maladaptive regulation of positive emotion has increasingly been associated with
      psychopathology. Little is known, however, about how individual strategies used
      to manage positive emotion predict concurrent emotional responding and
      prospective illness course across mood disorders. The present study examined the
      concurrent and prospective influence of amplification and dampening regulation
      strategies of positive emotion (i.e., self-focused positive rumination, emotion
      focused positive rumination, and dampening) among remitted individuals with
      bipolar I disorder (BD; n=31) and major depressive disorder (MDD; n=31).
      Rumination over positive emotional states concurrently predicted increased
      positive emotion across both mood disordered groups during an experimental
      rumination induction. However, dampening positive emotion concurrently predicted
      increased emotional reactivity (i.e., heart rate and negative affect) and
      prospective increases in manic and depressive symptoms for the BD group only.
      This suggests that amplifying positive emotion transdiagnostically increases
      positive emotion across mood disordered groups, while attempts to dampen positive
      emotion may paradoxically exacerbate emotional reactivity and illness course in
      BD. For individuals with BD, negative thinking about one's positive emotion (via
      dampening) may be particularly maladaptive.

PMID- 24076408
TI  - Implementation of cognitive therapy for PTSD in routine clinical care:
      effectiveness and moderators of outcome in a consecutive sample.
AB  - OBJECTIVE: Trauma-focused psychological treatments are recommended as first-line
      treatments for Posttraumatic Stress Disorder (PTSD), but clinicians may be
      concerned that the good outcomes observed in randomized controlled trials (RCTs)
      may not generalize to the wide range of traumas and presentations seen in
      clinical practice. This study investigated whether Cognitive Therapy for PTSD (CT
      PTSD) can be effectively implemented into a UK National Health Service Outpatient
      Clinic serving a defined ethnically mixed urban catchment area. METHOD: A
      consecutive sample of 330 patients with PTSD (age 17-83) following a wide range
      of traumas were treated by 34 therapists, who received training and supervision
      in CT-PTSD. Pre and post treatment data (PTSD symptoms, anxiety, depression) were
      collected for all patients, including dropouts. Hierarchical linear modeling
      investigated candidate moderators of outcome and therapist effects. RESULTS: CT
      PTSD was well tolerated and led to very large improvement in PTSD symptoms,
      depression and anxiety. The majority of patients showed reliable
      improvement/clinically significant change: intent-to-treat: 78.8%/57.3%;
      completer: 84.5%/65.1%. Dropouts and unreliable attenders had worse outcome.
      Statistically reliable symptom exacerbation with treatment was observed in only
      1.2% of patients. Treatment gains were maintained during follow-up (M=280 days,
      n=220). Few of the selection criteria used in some RCTs, demographic, diagnostic
      and trauma characteristics moderated treatment outcome, and only social problems
      and needing treatment for multiple traumas showed unique moderation effects.
      There were no random effects of therapist on symptom improvement, but therapists
      who were inexperienced in CT-PTSD had more dropouts than those with greater
      experience. CONCLUSIONS: The results support the effectiveness of CT-PTSD and
      suggest that trauma-focused cognitive behavior therapy can be successfully
      implemented in routine clinical services treating patients with a wide range of
      traumas.

PMID- 24076409
TI  - Host genetic factors respond to pathogenic step-specific virulence factors of
      Helicobacter pylori in gastric carcinogenesis.
AB  - The interindividual differences in risk of Helicobacter pylori (H. pylori)
      associated gastric cancer involve significant heterogeneities of both host
      genetics and H. pylori strains. Several recent studies proposed a distinct
      sequence for H. pylori exerting its virulence in the host stomach: (i) adhering
      to and colonizing the surface of gastric epithelial cells, (ii) evading and
      attenuating the host defense, and (iii) invading and damaging the gastric mucosa.
      This review focuses on several key issues that still need to be clarified, such
      as which virulence factors of H. pylori are involved in the three pathogenic
      steps, which host genes respond to the step-specific virulence factors, and
      whether and/or how the corresponding host genetic variations influence the risk
      of gastric carcinogenesis. Urease, BabA and SabA in the adhesion-step, PGN and
      LPS in the immune evasion-step, and CagA, VacA and Tipalpha in the mucosal damage
      step were documented to play an important role in step-specific pathogenicity of
      H. pylori infection. There is evidence further supporting a role of potentially
      functional polymorphisms of host genes directly responding to these pathogenic
      step-specific virulence factors in the susceptibility of gastric carcinogenesis,
      especially for urease-interacting HLA class II genes, BabA-interacting MUC1, PGN
      interacting NOD1, LPS-interacting TLR4, and CagA-interacting PTPN11 and CDH1.
      With the continuous improvement of understanding the genetic profile of H. pylori
      associated gastric carcinogenesis, a person at increased risk for gastric cancer
      may benefit from several aspects of efforts: (i) prevent H. pylori infection with
      a vaccine targeting certain step-specific virulence factor; (ii) eradicate H.
      pylori infection by blocking step-specific psychopathological characteristics of
      virulence factors; and (iii) adjust host physiological function to resist the
      carcinogenic role of step-specific virulence factors or interrupt the cellular
      signal transduction of the interplay between H. pylori and host in each
      pathogenic step, especially for the subjects with precancerous lesions in the
      stomach. 

PMID- 24076410
TI  - Cognitive interference and a food-related memory bias in binge eating disorder.
AB  - The present study was concerned with cognitive interference and a specific memory
      bias for eating-related stimuli in binge eating disorder (BED). Further
      objectives were to find out under which circumstances such effects would occur,
      and whether they are related with each other and with reported severity of BED
      symptoms. A group of women diagnosed with BED and a matched sample of overweight
      controls completed two paradigms, an n-back task with lures and a recent-probes
      task. The BED group generally experienced more interference in the n-back task.
      Additionally, they revealed selectively increased interference for food items in
      the recent-probes task. Findings can be reconciled with the view that control
      functions are generally impaired in BED, and that there is an additional bias for
      eating-related stimuli, both of which were related with reported severity of BED
      symptoms. 

PMID- 24076412
TI  - The potential neuroprotective effect of human adipose stem cells conditioned
      medium against light-induced retinal damage.
AB  - Human adipose-derived stem cells (hASCs) are present in adult adipose tissue and
      have been reported to secrete various factors that have neuroprotective effects.
      In the present study, we examined whether hASC-conditioned medium (hASC-CM) was
      effective against experimental degenerative retinal disease. Mature adipocytes
      (MAs) and hASCs were isolated from human subcutaneous adipose tissue. The
      isolated hASCs were identified based on their capacity for bone and neural
      differentiation. The effects of hASC-CM against tunicamycin-, H2O2-, and light
      induced retinal photoreceptor damage were evaluated in vitro by measuring cell
      death. Moreover, we identified various factors present in hASC-CM using antibody
      arrays. Retinal damage induced in mice by exposure to white light was studied in
      vivo, and photoreceptor damage was evaluated according to the thickness of the
      outer nuclear layer and electroretinography results. In addition, the effect of
      hASC-CM on Akt phosphorylation at Ser473 was confirmed by western blotting.
      Finally, the effects of the secreted proteins identified in the hASC-CM on light
      induced damage were evaluated in vivo. Isolated hASCs differentiated to
      osteocytes and neurons. hASC-CM protected against tunicamycin-, H2O2-, and light
      induced cell death. In addition, hASC-CM inhibited photoreceptor degeneration and
      retinal dysfunction after exposure to light. Several proteins secreted by hASCs,
      such as the tissue inhibitor of metalloproteinase-1 (TIMP-1) and the secreted
      protein acidic and rich in cysteine (SPARC), protected against light-induced
      damage in vitro and in vivo. The results of the present study showed that hASC-CM
      has neuroprotective effects against light-induced retinal damage and suggest that
      hASCs have a therapeutic potential in retinal degenerative diseases via their
      secreted proteins, without requiring transplantation. 

PMID- 24076411
TI  - Hypoxia-induced expression of VEGF splice variants and protein in four retinal
      cell types.
AB  - The purpose of this study was to investigate the hypoxia-induced Vegf120, Vegf164
      and Vegf188 mRNA expression profiles in rat Muller cells (MC), astrocytes,
      retinal pigmented epithelial cells (RPE) and retinal microvascular endothelial
      cells (RMEC) and correlate these findings to VEGF secreted protein. Cultured
      cells were exposed to normoxia or hypoxia. Total RNA was isolated from cell
      lysates and Vegf splice variant mRNA copy numbers were assayed by a validated qRT
      PCR external calibration curve method. mRNA copy numbers were normalized to input
      total RNA. Conditioned medium was collected from cells and assayed for total VEGF
      protein by ELISA. Hypoxia increased total Vegf mRNA and secreted protein in all
      the retinal cell types, with the highest levels observed in MC and astrocytes
      ranking second. Total Vegf mRNA levels in hypoxic RPE and RMEC were comparable;
      however, the greatest hypoxic induction of each Vegf splice variant mRNA was
      observed in RMEC. RPE and RMEC ranked 3rd and 4th respectively, in terms of
      secreted total VEGF protein in hypoxia. The Vegf120, Vegf164 and Vegf188 mRNA
      splice variants were all increased in hypoxic cells compared to normoxic
      controls. In normoxia, the relative Vegf splice variant mRNA levels ranked from
      highest to lowest for each cell type were Vegf164 > Vegf120 > Vegf188. Hypoxic
      induction did not alter this ranking, although it did favor an increased
      stoichiometry of Vegf164 mRNA over the other two splice variants. MC and
      astrocytes are likely to be the major sources of total Vegf, Vegf164 splice
      variant mRNAs, and VEGF protein in retinal hypoxia. 

PMID- 24076413
TI  - 1,25-Dihydroxyvitamin D decreases HTRA1 promoter activity in the rhesus monkey--a
      plausible explanation for the influence of vitamin D on age-related macular
      degeneration?
AB  - Age-related macular degeneration is the major cause of blindness in the elderly
      worldwide and the risk is influenced by both environmental and genetic risk
      factors. One important disease-associated region in humans is located on 10q26
      and includes the two candidate genes ARMS2 and HTRA1. However, determination of
      the causative gene has not yet been possible and examining the situation in the
      rhesus monkey may help understand the situation in humans. In a recent paper, we
      characterized the rhesus monkey 10q26-orthologue region on chromosome 9 in detail
      and identified the drusen-associated HTRA1 promoter SNP rs196357513 as a putative
      risk factor. In this study, we predicted 9 binding sites for the vitamin D
      dependent transcription factor vitamin D receptor in the rhesus HTRA1 promoter,
      one of which is destroyed by the rs196357513-risk allele. As patients with
      vitamin D deficit are at increased risk for age-related macular degeneration, a
      luciferase assay in transiently transfected ARPE19-cells was performed to
      evaluate the influence of the SNP rs196357513 and of 1,25-dihydroxyvitamin D on
      the rhesus monkey HTRA1 promoter activity. This revealed that the luciferase
      activity of the promoter construct containing the rs196357513 wild type allele
      was significantly reduced after vitamin D stimulation. An in silico analysis and
      literature search imply that this regulation could also play a role in human
      HTRA1 expression. Moreover, HTRA1 promoter activity of the construct containing
      the rs196357513 risk allele appeared diminished in comparison to the construct
      with the wild type allele, albeit this difference was not significant. The lower
      promoter activity due to the rhesus monkey rs196357513 risk allele apparently
      contradicts the common hypothesis for the human HTRA1 promoter risk allele of SNP
      rs11200638, for which a higher promoter activity has been observed. Our data
      point to a yet unexpected effect of decreased HTRA1 expression on drusen
      pathogenesis. Thus not only a higher HTRA1 expression, but an imbalance of HTRA1
      might be disease-relevant. Both findings require closer analysis, but if
      relevance for humans proves true, it would impact current age-related macular
      degeneration research and treatment. 

PMID- 24076414
TI  - Outcomes of liver transplantation for nonalcoholic steatohepatitis: a systematic
      review and meta-analysis.
AB  - BACKGROUND & AIMS: Little is known about outcomes of patients with nonalcoholic
      steatohepatitis (NASH) who receive liver transplants. We performed a systematic
      review and meta-analysis to estimate post-transplant outcomes, survival times,
      and mortality from cardiovascular complications, sepsis, and graft failure in
      these patients. METHODS: We searched PubMed and EMBASE, and Cochrane library and
      Web of Science databases for studies published through September 1, 2012 of
      patients who underwent liver transplantation for NASH or nonalcoholic fatty liver
      disease (NAFLD). All original studies from single institutions that reported
      outcomes of patients with or without NASH after liver transplantation were
      considered. Odds ratios (ORs) were calculated for patients with NASH, compared
      with patients without NASH; 95% confidence intervals (CIs) were calculated.
      RESULTS: Our final analysis included 9 publications, on 717 patients with NASH
      and 3520 without, all of whom underwent liver transplantation. Similar
      proportions of patients with and without NASH who received liver transplants
      survived for 1, 3, and 5 years (OR for survival of patient with NASH 1 year after
      liver transplantation, 0.77; 95% CI, 0.59-1.00; P = .05; OR 3 years after
      transplantation, 0.97; 95% CI, 0.67-1.40; P = .86; OR 5 years after
      transplantation, 1.09; 95% CI, 0.77-1.56; P = .63). Patients with NASH had a
      greater risk of death from cardiovascular complications after liver
      transplantation (OR, 1.65; 95% CI, 1.01-2.70; P = .05) and from sepsis (OR, 1.71;
      95% CI, 1.17-2.50; P = .006). However, patients with NASH were at lower risk of
      graft failure compared with patients without NASH (OR, 0.21; 95% CI, 0.05-0.89; P
      = .03). CONCLUSIONS: Similar proportions of patients with and without NASH
      survive for 1, 3, and 5 years after liver transplantation. However, patients with
      NASH are more likely to die from cardiovascular complications or sepsis. More
      attention and careful consideration are therefore required in selecting patients
      with NASH for liver transplantation, along with aggressive management of
      cardiovascular complications and sepsis after transplantation.

PMID- 24076415
TI  - Effects of coffee consumption, smoking, and hormones on risk for primary
      sclerosing cholangitis.
AB  - BACKGROUND & AIMS: Little is known about nongenetic risk factors for primary
      sclerosing cholangitis (PSC), except a possible protective effect of smoking. We
      investigated the relationship between environmental risk factors and
      susceptibility to PSC. METHODS: A questionnaire was distributed to patients with
      PSC, recruited from Oslo University Hospital Rikshospitalet in Norway through
      2011, and randomly chosen individuals from the Norwegian Bone Marrow Donor
      Registry (control subjects). Data were analyzed from 240 patients with PSC and
      245 control subjects, matched for gender and age. RESULTS: A lower proportion of
      patients with PSC were daily coffee drinkers than control subjects, both
      currently (76% vs 86%; odds ratio [OR], 0.52; 95% confidence interval [CI], 0.32
      0.82; P = .006) and at the age of 18 years (35% vs 49%; OR, 0.58; 95% CI, 0.40
      0.83; P = .003). The associations were mainly attributed to differences observed
      in men. Twenty percent of the patients were ever (current or former) daily
      smokers compared with 43% of control subjects (OR, 0.33; 95% CI, 0.22-0.50; P <
      .001). Ever daily smoking before PSC diagnosis was associated with older age at
      diagnosis (42 years vs 32 years; P < .001). Ever daily smoking (P < .001) and
      being a coffee drinker at the age of 18 years (P = .048) were independently and
      negatively associated with PSC. Fewer female patients with PSC than control
      subjects reported ever use of hormonal contraception (51% vs 85%; P < .001).
      Among female patients, there was a strong correlation between increasing number
      of children before the diagnosis of PSC and increasing age at diagnosis (r =
      0.63; P < .001). CONCLUSIONS: Coffee consumption and smoking might protect
      against development of PSC. In women, the disease might be influenced by hormonal
      factors.

PMID- 24076416
TI  - Long-term outcomes of patients with Wilson disease in a large Austrian cohort.
AB  - BACKGROUND & AIMS: Wilson disease is an autosomal recessive disorder that affects
      copper metabolism, leading to copper accumulation in liver, central nervous
      system, and kidneys. There are few data on long-term outcomes and survival from
      large cohorts; we studied these features in a well-characterized Austrian cohort
      of patients with Wilson disease. METHODS: We analyzed data from 229 patients
      diagnosed with Wilson disease from 1961 through 2013; 175 regularly attended a
      Wilson disease outpatient clinic and/or their physicians were contacted for
      information on disease and treatment status and outcomes. For 53 patients lost
      during the follow-up period, those that died and reasons for their death were
      identified from the Austrian death registry. RESULTS: The mean observation period
      was 14.8 +/- 11.4 years (range, 0.5-52.0 years), resulting in 3116 patient-years.
      Of the patients, 61% presented with hepatic disease, 27% with neurologic
      symptoms, and 10% were diagnosed by family screening at presymptomatic stages.
      Patients with a hepatic presentation were diagnosed younger (21.2 +/- 12.0 years)
      than patients with neurologic disease (28.8 +/- 12.0; P < .001). In 2% of
      patients, neither symptoms nor onset of symptoms could be determined with
      certainty. Most patients stabilized (35%) or improved on chelation therapy (26%
      fully recovered, 24% improved), but 15% deteriorated; 8% required a liver
      transplant, and 7.4% died within the observation period (71% of deaths were
      related to Wilson disease). A lower proportion of patients with Wilson disease
      survived for 20 years (92%) than healthy Austrians (97%), adjusted for age and
      sex (P = .03). Cirrhosis at diagnosis was the best predictor of death (odds
      ratio, 6.8; 95% confidence interval, 1.5-31.03; P = .013) and need for a liver
      transplant (odds ratio, 07; 95% confidence interval, 0.016-0.307; P < .001). Only
      84% of patients with cirrhosis survived 20 years after diagnosis (compared with
      healthy Austrians, P =.008). CONCLUSION: Overall, patients who receive adequate
      care for Wilson disease have a good long-term prognosis. However, cirrhosis
      increases the risk of death and liver disease. Early diagnosis, at a precirrhotic
      stage, might increase survival times and reduce the need for a liver transplant.

PMID- 24076417
TI  - Factors associated with response to therapy and outcome of patients with primary
      biliary cirrhosis with features of autoimmune hepatitis.
AB  - BACKGROUND & AIMS: For patients with primary biliary cirrhosis (PBC) with
      features of autoimmune hepatitis (AIH), treatment with ursodeoxycholic acid
      (UDCA) alone or in combination with immunosuppression is controversial. Little is
      known about the factors associated with initial response to therapy or outcome.
      We performed a retrospective analysis of treatment strategies and factors
      associated with outcomes of patients with PBC-AIH. METHODS: We analyzed data from
      88 patients who were diagnosed with PBC-AIH according to Paris criteria, from 7
      centers in 5 countries. First-line therapies included UDCA alone (n = 30) or a
      combination of UDCA and immunosuppression (n = 58). RESULTS: Of patients who
      received UDCA alone as the first-line therapy, 37% did not respond to treatment.
      Severe interface hepatitis was independently associated with lack of response to
      treatment (P = .024; odds ratio, 0.05; 95% confidence interval, 0.004-0.68). The
      combination of UDCA and immunosuppression was effective in 73% of patients who
      had not been previously treated or had not responded to UDCA. The presence of
      advanced fibrosis was associated with lack of response to the combination of UDCA
      and immunosuppression (P = .003; odds ratio, 0.13; 95% confidence interval, 0.03
      0.48). Second-line immunosuppressive agents (cyclosporine, tacrolimus, and
      mycophenolate mofetil) led to biochemical remission in 54% of patients who did
      not respond to initial immunosuppression. Liver transplants were given to 4
      patients with PBC-AIH. Five patients died during follow-up (3 from liver-related
      causes). CONCLUSIONS: In a retrospective study of a large cohort of patients with
      PBC-AIH, UDCA alone did not produce a biochemical response in most patients with
      severe interface hepatitis; these patients require additional therapy with
      immunosuppression. Second-line immunosuppressive agents are effective in
      controlling disease activity in patients who do not respond to conventional
      immunosuppression.

PMID- 24076418
TI  - Changes in cortical beta activity related to a biceps brachii movement task while
      experiencing exercise induced muscle damage.
AB  - Exercise-induced-muscle-damage (EIMD) is a well-described phenomenon which leads
      to decreased force output and altered neuromuscular function. How these symptoms
      of EIMD affect brain function, in particular cortical activity has not been
      described. Therefore the aim of this study was to investigate the relationship
      between the symptoms of EIMD and cortical beta (beta) activity during a
      submaximal biceps brachii movement. Half of the subjects participated in an EIMD
      protocol. Control and EIMD groups were monitored for 132h thereafter. Muscle pain
      scores in the EIMD group peaked after 36h with the lowest muscle torque reported
      at 12h. Beta-1 and -2 activity was increased in the frontal and parietal area in
      the experimental group at 12h. This suggests an impact of EIMD induced
      neuromuscular changes on the cortical proprioceptive and motor perceptive
      networks. Beta-2 activity decreased in the control group over time suggesting a
      loss in focused attention and greater familiarization with the protocol as the
      study progressed. These data suggest that a change in beta-1 and -2 activity is
      associated with integrating movement perception and proprioception post-EIMD. 

PMID- 24076419
TI  - Evolution and phylogeny of the corticotropin-releasing factor (CRF) family of
      peptides: expansion and specialization in the vertebrates.
AB  - New sequence data on CRF family members from a number of genomes has led to the
      modification of our understanding of CRF evolution in the Metazoa. The
      corticotropin-releasing factor (CRF) family of peptides include four paralogous
      lineages in jawed vertebrates; CRF, urotensin-I/urocortin/sauvagine, urocortin 2
      (Ucn2) and urocortin 3 (Ucn3). CRF and the urotensin-I/urocortin/sauvagine group
      represent a gene duplication from one lineage, whereas Ucns 2 and 3 are the
      result of a gene duplication in the other paralogous lineage. Both paralogous
      lineages are the result of a gene duplication from a single ancestral peptide
      that occurred after the divergence of the tunicates from the ancestor that led to
      the evolution of chordates and vertebrates. The presence of a single CRF-like
      peptide in tunicates and insects suggests that a single CRF-like ancestor was
      present before the separation of deuterostomes and protostomes. Currently there
      is no strong evidence that indicates that CRF-like peptides were present in
      metazoan taxa that evolved before this time although the structural similarity
      between some CRF peptides in insects, tunicates and vertebrates with the
      calcitonin family of peptides hints that prior to the formation of deuterostomes
      and protostomes the ancestral peptide possessed both CRF and calcitonin-like
      structural attributes. Here, we show evidences of conservation of CRF-like
      function dating back to early prokaryotes. This ancestral CRF-calcitonin-like
      peptide may have initially resulted from a horizontal gene transfer event from
      prokaryotes to a protistan species that later gave rise to the metazoans. 

PMID- 24076420
TI  - Role of phospholipases A2 in diabetic retinopathy: in vitro and in vivo studies.
AB  - Diabetic retinopathy is one of the leading causes of blindness and the most
      common complication of diabetes with no cure available. We investigated the role
      of phospholipases A2 (PLA2) in diabetic retinopathy using an in vitro blood
      retinal barrier model (BRB) and an in vivo streptozotocin (STZ)-induced diabetic
      model. Mono- and co-cultures of endothelial cells (EC) and pericytes (PC),
      treated with high or fluctuating concentrations of glucose, to mimic the diabetic
      condition, were used. PLA2 activity, VEGF and PGE2 levels and cell proliferation
      were measured, with or without PLA2 inhibition. Diabetes was induced in rats by
      STZ injection and PLA2 activity along with VEGF, TNFalpha and ICAM-1 levels were
      measured in retina. High or fluctuating glucose induced BRB breakdown, and
      increased PLA2 activity, PGE2 and VEGF in EC/PC co-cultures; inhibition of PLA2
      in mono- or co-cultures treated with high or fluctuating glucose dampened PGE2
      and VEGF production down to the levels of controls. High or fluctuating glucose
      increased EC number and reduced PC number in co-cultures; these effects were
      reversed after transfecting EC with small interfering RNA targeted to PLA2. PLA2
      and COX-2 protein expressions were significantly increased in microvessels from
      retina of diabetic rats. Diabetic rats had also high retinal levels of VEGF, ICAM
      1 and TNFalpha that were reduced by treatment with a cPLA2 inhibitor. In
      conclusion, the present findings indicate that PLA2 upregulation represents an
      early step in glucose-induced alteration of BRB, possibly upstream of VEGF; thus,
      PLA2 may be an interesting target in managing diabetic retinopathy. 

PMID- 24076422
TI  - Stopped-flow fluorescence kinetic study of protein sliding and intersegment
      transfer in the target DNA search process.
AB  - Kinetic characterizations of protein translocation on DNA are nontrivial because
      the simultaneous presence of multiple different mechanisms makes it difficult to
      extract the information specific to a particular translocation mechanism. In this
      study, we have developed new approaches for the kinetic investigations of
      proteins' sliding and intersegment transfer (also known as "direct transfer") in
      the target DNA search process. Based on the analytical expression of the mean
      search time for the discrete-state stochastic model, we derived analytical forms
      of the apparent rate constant kapp for protein-target association in systems
      involving competitor DNA and the intersegment transfer mechanism. Our analytical
      forms of kapp facilitate the experimental determination of the kinetic rate
      constants for intersegment transfer and sliding in the target association
      process. Using stopped-flow fluorescence data for the target association kinetics
      along with the analytical forms of kapp, we have studied the translocation of the
      Egr-1 zinc-finger protein in the target DNA association process. Sliding was
      analyzed using the DNA-length-dependent kapp data. Using the dependence of kapp
      on the concentration of competitor DNA, we determined the second-order rate
      constant for intersegment transfer. Our results indicate that a major pathway in
      the target association process for the Egr-1 zinc-finger protein is the one
      involving intersegment transfer to a nonspecific site and the subsequent sliding
      to the target. 

PMID- 24076421
TI  - IFITMs restrict the replication of multiple pathogenic viruses.
AB  - The interferon-inducible transmembrane protein (IFITM) family inhibits a growing
      number of pathogenic viruses, among them influenza A virus, dengue virus,
      hepatitis C virus, and Ebola virus. This review covers recent developments in our
      understanding of the IFITM's molecular determinants, potential mechanisms of
      action, and impact on pathogenesis. 

PMID- 24076423
TI  - Vertical-plane sound localization with distorted spectral cues.
AB  - For human listeners, the primary cues for localization in the vertical plane are
      provided by the direction-dependent filtering of the pinnae, head, and upper
      body. Vertical-plane localization generally is accurate for broadband sounds, but
      when such sounds are presented at near-threshold levels or at high levels with
      short durations (<20 ms), the apparent location is biased toward the horizontal
      plane (i.e., elevation gain <1). We tested the hypothesis that these effects
      result in part from distorted peripheral representations of sound spectra. Human
      listeners indicated the apparent position of 100-ms, 50-60 dB SPL, wideband noise
      burst targets by orienting their heads. The targets were synthesized in virtual
      auditory space and presented over headphones. Faithfully synthesized targets were
      interleaved with targets for which the directional transfer function spectral
      notches were filled in, peaks were leveled off, or the spectral contrast of the
      entire profile was reduced or expanded. As notches were filled in progressively
      or peaks leveled progressively, elevation gain decreased in a graded manner
      similar to that observed as sensation level is reduced below 30 dB or, for brief
      sounds, increased above 45 dB. As spectral contrast was reduced, gain dropped
      only at the most extreme reduction (25% of normal). Spectral contrast expansion
      had little effect. The results are consistent with the hypothesis that loss of
      representation of spectral features contributes to reduced elevation gain at low
      and high sound levels. The results also suggest that perceived location depends
      on a correlation-like spectral matching process that is sensitive to the
      relative, rather than absolute, across-frequency shape of the spectral profile.

PMID- 24076425
TI  - Phase effects in masking by harmonic complexes: speech recognition.
AB  - Harmonic complexes that generate highly modulated temporal envelopes on the
      basilar membrane (BM) mask a tone less effectively than complexes that generate
      relatively flat temporal envelopes, because the non-linear active gain of the BM
      selectively amplifies a low-level tone in the dips of a modulated masker
      envelope. The present study examines a similar effect in speech recognition.
      Speech reception thresholds (SRTs) were measured for a voice masked by harmonic
      complexes with partials in sine phase (SP) or in random phase (RP). The masker's
      fundamental frequency (F0) was 50, 100 or 200 Hz. SRTs were considerably lower
      for SP than for RP maskers at 50-Hz F0, but the two converged at 100-Hz F0, while
      at 200-Hz F0, SRTs were a little higher for SP than RP maskers. The results were
      similar whether the target voice was male or female and whether the masker's
      spectral profile was flat or speech-shaped. Although listening in the masker dips
      has been shown to play a large role for artificial stimuli such as Schroeder
      phase complexes at high levels, it contributes weakly to speech recognition in
      the presence of harmonic maskers with different crest factors at more moderate
      sound levels (65 dB SPL).

PMID- 24076426
TI  - Manipulating number generation: loud + long = large?
AB  - Humans make numerous choices every day and tend to perceive these choices as
      free. The present study shows how simple free choices are biased by experiencing
      unrelated auditory information. In two experiments, participants categorized
      tones according to their intensity on the dimensions volume and duration on the
      majority of trials. On some trials, however, they were to randomly generate a
      number, and we found these choices to be influenced by tone intensity.
      Particularly, if participants were cued toward volume, loud tones clearly biased
      participants to generate larger numbers. For tone duration, a similar effect only
      emerged if spatial information was reinforced by the motor context of the task.
      The findings extend previous findings relating to the ATOM framework (A Theory of
      Magnitude) by an explicit focus on auditory magnitude processing. As such, they
      also constrain ATOM by showing that the connections between different magnitude
      dimensions vary to a considerable degree. 

PMID- 24076424
TI  - Auditory neuroimaging with fMRI and PET.
AB  - For much of the past 30 years, investigations of auditory perception and language
      have been enhanced or even driven by the use of functional neuroimaging
      techniques that specialize in localization of central responses. Beginning with
      investigations using positron emission tomography (PET) and gradually shifting
      primarily to usage of functional magnetic resonance imaging (fMRI), auditory
      neuroimaging has greatly advanced our understanding of the organization and
      response properties of brain regions critical to the perception of and
      communication with the acoustic world in which we live. As the complexity of the
      questions being addressed has increased, the techniques, experiments and analyses
      applied have also become more nuanced and specialized. A brief review of the
      history of these investigations sets the stage for an overview and analysis of
      how these neuroimaging modalities are becoming ever more effective tools for
      understanding the auditory brain. We conclude with a brief discussion of open
      methodological issues as well as potential clinical applications for auditory
      neuroimaging. This article is part of a Special Issue entitled Human Auditory
      Neuroimaging.

PMID- 24076427
TI  - Insights into the regulation of GPEET procyclin during differentiation from early
      to late procyclic forms of Trypanosoma brucei.
AB  - The procyclic form of Trypanosoma brucei colonises the gut of its insect vector,
      the tsetse fly. GPEET and EP procyclins constitute the parasite's surface coat at
      this stage of the life cycle, and the presence or absence of GPEET distinguishes
      between early and late procyclic forms, respectively. Differentiation from early
      to late procyclic forms in vivo occurs in the fly midgut and can be mimicked in
      culture. Our analysis of this transition in vitro delivered new insights into the
      process of GPEET repression. First, we could show that parasites followed a
      concrete sequence of events upon triggering differentiation: after undergoing an
      initial growth arrest, cells lost GPEET protein, and finally late procyclic forms
      resumed proliferation. Second, we determined the stability of both GPEET and EP
      mRNA during differentiation. GPEET mRNA is exceptionally stable in early
      procyclic forms, with a half-life >6h. The GPEET mRNA detected in late procyclic
      form cultures is a mixture of transcripts from both bona fide late procyclic
      forms and GPEET-positive 'laggard' parasites present in these cultures. However,
      its stability was clearly reduced during differentiation and in late procyclic
      form cultures. Alternatively processed GPEET transcripts were enriched in samples
      from late procyclic forms, suggesting that altered mRNA processing might
      contribute to repression of GPEET in this developmental stage. In addition, we
      detected GPEET transcripts with non-templated oligo(U) tails that were enriched
      in late procyclic forms. To the best of our knowledge, this is the first study
      reporting a uridylyl-tailed, nuclear-encoded mRNA species in trypanosomatids or
      any other protozoa. 

PMID- 24076428
TI  - Circumvention of resistance to photodynamic therapy in doxorubicin-resistant
      sarcoma by photochemical internalization of gelonin.
AB  - A wide range of anti-cancer therapies have been shown to induce resistance upon
      repetitive treatment and such adapted resistance may also cause cross-resistance
      to other treatment modalities. We here show that MES-SA/Dx5 cells with adapted
      resistance to doxorubicin (DOX) are cross-resistant to photodynamic therapy
      (PDT). A DOX-induced increased expression of the reactive oxygen species (ROS)
      scavenging proteins glutathione peroxidase (GPx) 1 and GPx4 in MES-SA/Dx5 cells
      was indicated as the mechanism of resistance to PDT in line with the reduction in
      PDT-generated ROS observed in this cell line. ROS-induced p38 activation was, in
      addition, shown to be reduced to one-third of the signal of the parental MES-SA
      cells 2h after PDT, and addition of the p38 inhibitor SB203580 confirmed p38
      activation as a death signal after PDT in the MES-SA cells. The MES-SA/Dx5 cells
      were also cross-resistant to ionizing radiation in agreement with the increased
      GPx1 and GPx4 expression. Surprisingly, PDT-induced endo/lysosomal release of the
      ribosome-inactivating protein gelonin (photochemical internalization (PCI)) was
      more effective in the PDT-resistant MES-SA/Dx5 cells, as measured by synergy
      calculations in both cell lines. Analysis of death-inducing signaling indicated a
      low activation of caspase-3 and a strong PARP I cleavage after PDT and PCI in
      both cell lines. The PARP I activation was, however, stronger after PCI than
      after PDT in the MES-SA cells, but not in the MES-SA/Dx5 cells, and therefore
      cannot explain the strong PCI effect in the MES-SA/Dx5 cells. In conclusion PCI
      of recombinant gelonin circumvents ROS resistance in an apoptosis-independent
      manner. 

PMID- 24076430
TI  - Tacrolimus toxicity following topical treatment of perianal Crohn's disease: an
      admonitory anecdote.

PMID- 24076431
TI  - IL-33 mediates the expressions of IL-5 and IL-13 in Angiostrongylus cantonensis
      infected mice.
AB  - Angiostrongylus cantonensis is the major cause of human eosinophilic
      meningoencephalitis. C57BL/6 mice were experimentally infected with 35 infectious
      larvae. Two groups of infected mice received intraperitoneal injections of mouse
      IL-33 (1MUg) or anti-IL-33 monoclonal antibody (mAb) (10MUg) 3days post infection
      (dpi) and subsequent booster shots of the same dose at 5day intervals. Blood
      samples from each group were collected weekly for assays. IgE levels were
      significantly increased in all infected mice. The eosinophil percentage and
      levels of IL-5 and IL-13 significantly increased in the IL-33-treated group
      relative to infected but non-treated animals. The level of IL-5 decreased in the
      mAb-treated group. The severity of eosinophilic meningitis was exacerbated in the
      IL-33 injected group. Taken together, these results suggest that IL-33 mediates
      the expressions of IL-5 and IL-13, and plays a crucial role in the pathogenesis
      of angiostrongylosis. 

PMID- 24076432
TI  - Degree of anemia correlates with increased utilization of heme by Leishmania
      donovani parasites in visceral leishmaniasis.
AB  - Anemia in kala-azar patients is a serious problem. The present study has
      addressed this problem with the hypothesis that as the Leishmania parasite is
      completely devoid of heme biosynthetic pathway, therefore the excessive use of
      heme by the parasites in the human patients can be one of the possible reason of
      anemia. We investigated that whether, the inability of Leishmania donovani to
      synthesize heme, can enforce Leishmania parasite to utilize heme derived from
      host sources in Indian KA patients. Patients had higher tendency of their
      macrophages to bind with Hb which was pronounced after sensitization with drug
      resistant Leishmania strain compared to sensitive. 

PMID- 24076429
TI  - Imaging Plasmodium immunobiology in the liver, brain, and lung.
AB  - Plasmodium falciparum malaria is responsible for the deaths of over half a
      million African children annually. Until a decade ago, dynamic analysis of the
      malaria parasite was limited to in vitro systems with the typical limitations
      associated with 2D monocultures or entirely artificial surfaces. Due to extremely
      low parasite densities, the liver was considered a black box in terms of
      Plasmodium sporozoite invasion, liver stage development, and merozoite release
      into the blood. Further, nothing was known about the behavior of blood stage
      parasites in organs such as the brain where clinical signs manifest and the
      ensuing immune response of the host that may ultimately result in a fatal
      outcome. The advent of fluorescent parasites, advances in imaging technology, and
      availability of an ever-increasing number of cellular and molecular probes have
      helped illuminate many steps along the pathogenetic cascade of this deadly
      tropical parasite. 

PMID- 24076433
TI  - Synthesis and antiviral evaluation of 6'-acylamido-6'-deoxy-alpha-D
      mannoglycerolipids.
AB  - Eight new aminomannoglycerolipids (2a-h) with linear, branched, or aromatic acyl
      chains were synthesized and evaluated for their anti-influenza A virus (IAV)
      activity. By comparing six mannosyl donors with different protecting and leaving
      groups, the critical glycosylation reaction employed mannosyl
      trichloroacetimidate with 2-O-benzoyl protecting group as the donor to give the
      glycoside with absolute alpha-anomeric selectivity. The bioactivity results
      showed that the branched compound 2g could effectively inhibit IAV multiplication
      in MDCK cells with IC50 69.9MUM. 

PMID- 24076434
TI  - Ghrelin and peptide YY increase with weight loss during a 12-month intervention
      to reduce dietary energy density in obese women.
AB  - Reducing dietary energy density (ED) promotes weight loss; however, underlying
      mechanisms are not well understood. The purpose of this study was to determine if
      low-ED diets facilitate weight loss through actions on ghrelin and peptide YY
      (PYY), independent of influences of psychosocial measures. Seventy-one obese
      women (BMI 30-40 kg/m(2)) ages 22-60 years received counseling to reduce ED.
      Fasting blood samples were analyzed for total ghrelin and total PYY by
      radioimmunoassay at months 0, 3, 6, and 12. Restraint, disinhibition, and hunger
      were assessed by the Eating Inventory. Body weight (-7.8 +/- 0.5 kg), BMI (-2.9
      +/- 0.2 kg/m(2)), body fat (-3.0 +/- 0.3%), and ED (-0.47 +/- 0.05 kcal/g or 
      1.97 +/- 0.21 kJ/g) decreased from months 0 to 6 (p<0.05) after which no change
      occurred from months 6 to 12. Ghrelin increased in a curvilinear fashion (month
      0: 973 +/- 39, month 3: 1024 +/- 37, month 6: 1109 +/- 44, and month 12: 1063 +/-
      45 pg/ml, p<0.001) and PYY increased linearly (month 0: 74.2 +/- 3.1, month 3:
      76.4 +/- 3.2, month 6: 77.2 +/- 3.0, month 12: 82.8 +/- 3.2 pg/ml, p<0.001). ED,
      body weight, and hunger predicted ghrelin, with ED being the strongest predictor
      (ghrelin = 2674.8+291.6 * ED-19.2 * BW-15 * H; p<0.05). There was a trend toward
      a significant association between ED and PYY (PYY = 115.0-43.1 * ED; p = 0.05).
      Reductions in ED may promote weight loss and weight loss maintenance by opposing
      increases in ghrelin and promoting increases in PYY.

PMID- 24076435
TI  - Discovery of clinical pathway patterns from event logs using probabilistic topic
      models.
AB  - Discovery of clinical pathway (CP) patterns has experienced increased attention
      over the years due to its importance for revealing the structure, semantics and
      dynamics of CPs, and to its usefulness for providing clinicians with explicit
      knowledge which can be directly used to guide treatment activities of individual
      patients. Generally, discovery of CP patterns is a challenging task as treatment
      behaviors in CPs often have a large variability depending on factors such as
      time, location and patient individual. Based on the assumption that CP patterns
      can be derived from clinical event logs which usually record various treatment
      activities in CP executions, this study proposes a novel approach to CP pattern
      discovery by modeling CPs using mixtures of an extension to the Latent Dirichlet
      Allocation family that jointly models various treatment activities and their
      occurring time stamps in CPs. Clinical case studies are performed to evaluate the
      proposed approach via real-world data sets recording typical treatment behaviors
      in patient careflow. The obtained results demonstrate the suitability of the
      proposed approach for CP pattern discovery, and indicate the promise in research
      efforts related to CP analysis and optimization. 

PMID- 24076436
TI  - Understanding semantic mapping evolution by observing changes in biomedical
      ontologies.
AB  - Knowledge Organization Systems (KOSs) are extensively used in the biomedical
      domain to support information sharing between software applications. KOSs are
      proposed covering different, but overlapping subjects, and mappings indicate the
      semantic relation between concepts from two KOSs. Over time, KOSs change as do
      the mappings between them. This can result from a new discovery or a revision of
      existing knowledge which includes corrections of concepts or mappings. Indeed,
      changes affecting KOS entities may force the underline mappings to be updated in
      order to ensure their reliability over time. To tackle this open research
      problem, we study how mappings are affected by KOS evolution. This article
      presents a detailed descriptive analysis of the impact that changes in KOS have
      on mappings. As a case study, we use the official mappings established between
      SNOMED CT and ICD-9-CM from 2009 to 2011. Results highlight factors according to
      which KOS changes in varying degrees influence the evolution of mappings. 

PMID- 24076437
TI  - Summarizing techniques that combine three non-parametric scores to detect disease
      associated 2-way SNP-SNP interactions.
AB  - Identifying susceptibility genes that influence complex diseases is extremely
      difficult because loci often influence the disease state through genetic
      interactions. Numerous approaches to detect disease-associated SNP-SNP
      interactions have been developed, but none consistently generates high-quality
      results under different disease scenarios. Using summarizing techniques to
      combine a number of existing methods may provide a solution to this problem. Here
      we used three popular non-parametric methods-Gini, absolute probability
      difference (APD), and entropy-to develop two novel summary scores, namely
      principle component score (PCS) and Z-sum score (ZSS), with which to predict
      disease-associated genetic interactions. We used a simulation study to compare
      performance of the non-parametric scores, the summary scores, the scaled-sum
      score (SSS; used in polymorphism interaction analysis (PIA)), and the multifactor
      dimensionality reduction (MDR). The non-parametric methods achieved high power,
      but no non-parametric method outperformed all others under a variety of epistatic
      scenarios. PCS and ZSS, however, outperformed MDR. PCS, ZSS and SSS displayed
      controlled type-I-errors (<0.05) compared to GS, APDS, ES (>0.05). A real data
      study using the genetic-analysis-workshop 16 (GAW 16) rheumatoid arthritis
      dataset identified a number of interesting SNP-SNP interactions. 

PMID- 24076438
TI  - Genetic variants and effects on milk traits of the caprine paired-like
      homeodomain transcription factor 2 (PITX2) gene in dairy goats.
AB  - The paired-like homeodomain transcription factor 2 (PITX2) gene plays a critical
      role in cell proliferation, differentiation, hematopoiesis and organogenesis.
      This gene regulates several genes' expressions in the Wnt/beta-catenin and POU1F1
      pathways, thereby probably affecting milk performance. The goal of this study was
      to characterize the genetic variants of the PITX2 gene and test their
      associations with milk traits in dairy goats. Herein, four novel single
      nucleotide polymorphisms (SNPs), AC_000163:g.18117T>C, g.18161C>G, g.18322C>A and
      g.18353T>C, within the caprine PITX2 gene, were found in two famous Chinese dairy
      goat breeds. These SNPs mapping at Cys28Arg, Pro42Pro, IVS1+79C>A and
      IVS1+110T>C, were genotyped by the MvaI, SmaI, MspI and RsaI aCRS-RFLP or PCR
      RFLP methods, respectively. Accordingly, two main haplotypes (CGCT and CGCC) were
      identified among the specimens. Association testing revealed that the SmaI and
      RsaI polymorphisms were significantly associated with the milk fat content, milk
      lactose content and milk density (P<0.05 or P<0.01) in the Guanzhong (GZ) dairy
      goats, respectively. At the same time, the RsaI locus was also found to
      significantly link to the second lactation milk yield, milk fat content, milk
      lactose content, milk density and milk total solid content (P<0.05 or P<0.01) in
      the Xinong Saanen (XNSN) dairy goats, respectively. These results indicated that
      the caprine PITX2 gene had the significant effects on milk traits. Hence, the
      RsaI and SmaI loci could be regarded as two DNA markers for selecting superior
      milk performance in dairy goats. These preliminary findings not only would extend
      the spectrum of genetic variation of the goat PITX2 gene, but also would
      contribute to implementing marker-assisted selection (MAS) in breeding and
      genetics in dairy goats.

PMID- 24076439
TI  - Impact of genetic polymorphisms in base excision repair genes on the risk of
      breast cancer in a Korean population.
AB  - The contribution of single nucleotide polymorphisms (SNPs) in base excision
      repair (BER) genes to the risk of breast cancer (BC) was evaluated by focusing on
      two key genes: apurinic/apyrimidinic endonuclease 1 (APEX1) and 8-oxoguanine DNA
      glycosylase (OGG1). Genetic variations in the genes encoding these DNA repair
      enzymes may alter their functions and increase susceptibility to carcinogenesis.
      The aim of this study was to analyze polymorphisms in two BER genes, exploring
      their associations and particularly the combined effects of these variants on BC
      risk in a Korean population. Three SNPs of two BER genes were genotyped using the
      Illumina GoldenGateTM method. In total, 346 BC patients and 361 cancer-free
      controls were genotyped for these BER gene polymorphisms and analyzed for their
      correlation with BC risk in multiple logistic regression models. Multiple
      logistic regression models adjusted for age, family history of BC, and body mass
      index were used. The APEX1 Asp148Glu polymorphism was weakly associated with BC
      risk. The combined analysis among the BER genes, however, showed significant
      effects on BC risk. The APEX1 Asp148Glu carrier, in combination with OGG1
      rs2072668 and OGG1 Ser326Cys, was strongly associated with an increased risk of
      BC. Moreover, the combination of the C-C haplotype of OGG1 with the APEX1
      Asp148Glu genotype was also associated with an additive risk effect of BC
      [ORs=2.44, 2.87, and 3.50, respectively]. The combined effect of APEX1 Asp148Glu
      was found to be associated with an increased risk of BC. These results suggest
      that the combined effect of different SNPs within BER genes may be useful in
      predicting BC risk.

PMID- 24076440
TI  - Interleukin-23 receptor genetic variants contribute to susceptibility of multiple
      cancers.
AB  - AIM: Interleukin-23 (IL-23) and IL-23 receptor (IL23R) play an important role
      during the T-helper 17 (Th17) cell-mediated inflammatory process as well as
      pathogenesis of multiple cancers. Several IL-23R single nucleotide polymorphisms
      (SNPs), especially rs6682925, rs10889677 and rs1884444 polymorphisms, are
      considered to have significant impacts on susceptibility of multiple cancers. A
      number of case-control studies have explored the role these genetic polymorphisms
      in development of carcinogenesis, but the conclusions are inconsistent.
      Therefore, we conducted this meta-analysis to systematically investigate the
      associations between the three genetic variants and multiple cancer risk.
      METHODS: A total of ten studies are eligible (12,211 patients and 14,650
      controls). Pooled odds ratios (ORs) and the 95% confidence interval (95% CI) were
      appropriately calculated using either fixed-effect model or random-effect model.
      RESULTS: Significant associations between rs6682925 or rs10889677 polymorphism
      and cancer risk were found (OR=1.11, 95% CI=1.03-1.21, P=0.007; or OR=0.85, 95%
      CI=0.71-0.92, P=0.001). However, there was no such association between rs1884444
      genotypes and cancer susceptibility (P>0.05). CONCLUSION: These findings reveal
      that the IL-23R rs6682925 and rs10889677 genetic variants play a more important
      part in pathogenesis of multiple cancers.

PMID- 24076441
TI  - Cervical kinematics and radiological changes after Discover artificial disc
      replacement versus fusion.
AB  - BACKGROUND CONTEXT: The cervical disc arthroplasty has emerged as a promising
      alternative to the anterior cervical discectomy and fusion (ACDF) in patients
      with radiculopathy or myelopathy with disc degeneration disease. The advantages
      of this technique have been reported to preserve the cervical mobility and
      possibly reduce the adjacent segment degeneration. However, no studies have
      compared the clinical outcomes and radiological results in patients treated with
      Discover artificial disc replacement to those observed in matched group of
      patients that have undergone ACDF. PURPOSE: We conducted this clinical study to
      compare the cervical kinematics and radiographic adjacent-level changes after
      Discover artificial disc replacement with ACDF. STUDY DESIGN: Analysis and
      evaluation of data acquired in a comparative clinical study. PATIENT SAMPLE: The
      number of patients in the Discover and ACDF group were 149 and 196, respectively.
      OUTCOME MEASURES: The Neck Disability Index (NDI) and visual analog scale (VAS)
      pain score were evaluated. The range of movement (ROM) by the shell angle, the
      functional segment unit and global angles were measured, and the postoperative
      radiological changes at adjacents levels were observed. METHODS: A total of 149
      patients with symptomatic single or two-level cervical degenerative diseases
      received the Discover cervical artificial disc replacement from November 2008 to
      February 2010. During the same period, there were a total of 196 patients
      undergoing one or two-level ACDF. The average follow-up periods of the Discover
      disc group and ACDF group were 22.1 months and 22.5 months, respectively. Before
      surgery, patients were evaluated using static and dynamic cervical spine
      radiographs in addition to computerized tomography and magnetic resonance
      imaging. Static and dynamic cervical spine radiographs were obtained after
      surgery and then at 3- and 6-month follow-up. Then, the subsequent follow-up
      examinations were performed at every 6-month interval. The clinical results in
      terms of NDI and VAS scores, the parameters of cervical kinematics, postoperative
      radiological changes at adjacent levels, and complications in the two groups were
      statistically analyzed and compared. No funding was received for this study, and
      the authors report no potential conflict of interest-associated biases in the
      text. RESULTS: Although the clinical improvements in terms of NDI and VAS scores
      were achieved in both the Discover and ACDF group, no significant difference was
      found between the two groups for both single- (VAS p=.13, NDI p=.49) and double
      level surgeries (VAS p=.28, NDI p=.21). Significant differences of cervcial
      kinematics occurred between the Discover and the ACDF group for both the single-
      and double-level surgeries at the operative segments (p<.001). Except the upper
      adjacent levels for the single-level Discover and ACDF groups (p=.33),
      significant increases in adjacent segment motion were observed in the ACDF group
      compared with the minimal ROM changes in adjacent segment motion noted in the
      Discover group, and the differences between the two groups for both single and
      double-level procedures were statistically significant (p<.05). There were
      significant differences in the postoperative radiological changes at adjacent
      levels between the Discover and ACDF groups for the single-level surgery (p<.001,
      chi(2)=18.18) and the double-level surgery (p=.007, chi2=7.2). No significant
      difference of complications was found between the Discover and ACDF groups in
      both single (p=.25, chi2=1.32) and double-level cases (p=.4, chi2=0.69).
      CONCLUSIONS: The adjacent segment ROM and the incidence of radiographic adjacent
      level changes in patients undergoing ACDF were higher than those undergoing
      Discover artificial disc replacement. The cervical mobility was relatively well
      maintained in the Discover group compared with the ACDF group, and the Discover
      cervical disc arthroplasty can be an effective alternative to the fusion
      technique.

PMID- 24076442
TI  - Accurately measuring the quality and effectiveness of cervical spine surgery in
      registry efforts: determining the most valid and responsive instruments.
AB  - BACKGROUND CONTEXT: There is a growing demand to measure the real-world
      effectiveness and value of care across all specialties and disease states.
      Prospective registries have emerged as a feasible way to capture real-world care
      across large patient populations. However, the proven validity of more robust and
      cumbersome patient-reported outcome instruments (PROi) must be balanced with what
      is feasible to apply in large-scale registry efforts. Hence, commercial registry
      efforts that measure quality and effectiveness of care in an attempt to guide
      quality improvement, pay for performance, or value-based purchasing should
      incorporate measures that most accurately represent patient-centered improvement.
      PURPOSE: We set out to establish the relative validity and responsiveness of
      common PROi in accurately determining effectiveness of cervical surgery for neck
      and arm pain in registry efforts. STUDY DESIGN: Prospective cohort study. PATIENT
      SAMPLE: Eighty-eight patients undergoing primary anterior cervical discectomy and
      fusion (ACDF) for neck and arm pain. OUTCOME MEASURES: Patient-reported outcome
      measures for pain (numeric rating scale for neck pain [NRS-NP] and arm pain [NRS
      AP]), disability (neck disability index [NDI]), general health (short-form 12
      item survey physical component summary [SF-12 PCS] and mental component summary
      [SF-12 MCS]), and quality of life (Euro-Qol-5D [EQ-5D]) were assessed. METHODS:
      Eighty-eight patients undergoing primary ACDF for neck and arm pain were entered
      into a Web-based prospective registry. Baseline and 12-month patient-reported
      outcomes (NRS-NP, NRS-AP, NDI, SF-12 PCS, SF-12 MCS, and EQ-5D) were assessed.
      Patients were also asked whether they experienced a level of improvement after
      ACDF that met their expectation (meaningful improvement). To assess the validity
      of NRS-NP, NRS-AP, and NDI (measures of pain and disability) to discriminate
      between meaningful and nonmeaningful improvement and the validity of SF-12 PCS,
      SF-12 MCS, and EQ-5D (measures of general health and quality of life) to
      discriminate between meaningful and nonmeaningful improvement, receiver-operating
      characteristic curves were generated for each outcome instrument. The greater the
      area under the curve (AUC), the more valid the discriminator. The difference
      between standardized response means (SRMs) in patients reporting meaningful
      improvement versus not was calculated to determine the relative responsiveness of
      each outcome instrument to changes in pain and QOL after surgery. RESULTS: For
      pain and disability, both NDI (AUC=0.75) and NRS-AP (AUC=0.74) were valid
      discriminators of meaningful improvement. Numeric rating scale for neck pain
      (AUC=0.69) was a poor discriminator. Neck disability index was also most
      responsive to postoperative improvement (SRM difference 0.78), followed by NRS-AP
      (SRM difference 0.59) and NRS-NP (SRM difference 0.46). For general health and
      quality of life, SF-12 PCS (AUC=0.79) was the only valid discriminator of
      meaningful improvement. Euro-Qol-5D (AUC=0.68) and SF-12 MCS (AUC=0.44) were poor
      discriminators. Short-form 12 physical component summary (SRM difference 1.08)
      was also most responsive compared with EQ-5D (SRM difference 0.89) and SF-12 MCS
      (SRM difference 0.01). CONCLUSIONS: For pain and disability, NDI is the most
      valid and responsive measure of improvement after surgery for neck and arm pain.
      Numeric rating scale for neck pain and NRS-AP are poor substitutes for NDI when
      measuring effectiveness of care in registry efforts. For health-related quality
      of life, only SF-12 PCS could accurately discriminate meaningful improvement
      after cervical surgery and was found to be most valid and responsive. Large-scale
      registry efforts aimed at measuring effectiveness of cervical spine surgery
      should use NDI and SF-12 to accurately assess improvements in pain, disability,
      and quality of life.

PMID- 24076443
TI  - Characteristics and surgical management of neuropathic (Charcot) spinal
      arthropathy after spinal cord injury.
AB  - BACKGROUND CONTEXT: Neuropathic (Charcot) spinal arthropathy (CSA) is a rare but
      progressive and severe degenerative disease that develops in the absence of deep
      sensation, for example, after spinal cord injury. The diagnosis of CSA is often
      delayed as a result of the late onset or slow progression of the disease and the
      nonspecific nature of the reported clinical signs. Considering risk factors of
      CSA in combination with the common clinical signs may facilitate timely diagnosis
      and prevent severe presentation of the disease. However, there is a lack of data
      concerning the early signs and risk factors of CSA. Furthermore, the
      complications and outcomes after surgical treatment are documented
      insufficiently. PURPOSE: To investigate the early signs and risk factors of CSA
      after spinal cord injury, as well as the complications and outcome after surgical
      treatment. STUDY DESIGN: Retrospective case series from a single center. PATIENT
      SAMPLE: Twenty-eight patients with 39 Charcot joints of the spine. OUTCOME
      MEASURES: Clinical signs, radiological signs, risk factors, and complications.
      METHODS: The case histories and radiological images of patients suffering from
      CSA were investigated. RESULTS: The first clinical symptoms included spinal
      deformity, sitting imbalance, and localized back pain. Long-segment
      stabilization, laminectomy, scoliosis, and excessive loading of the spine were
      identified as risk factors for the development of the disease. Postoperative
      complications included implant loosening, wound healing disturbance, and
      development of additional Charcot joints. All patients were able to return to
      their previous levels of activities. CONCLUSIONS: Radiological follow-up of the
      entire thoracic and lumbar spine should be performed in paraplegic patients. Risk
      factors in combination with typical symptoms should be considered to facilitate
      early detection. Functional restoration can be achieved with appropriate surgical
      techniques.

PMID- 24076444
TI  - Relationship between left atrial appendage morphology and stroke in patients with
      atrial fibrillation.
AB  - BACKGROUND: Atrial fibrillation (AF) is an important cause of stroke. Given the
      morbidity and mortality associated with stroke, the risk stratification of
      patients based on left atrial appendage (LAA) characteristics is of great
      interest. OBJECTIVE: To explore the association between LAA morphology and LAA
      characteristics including the extent of trabeculations, orifice diameter, and
      length with prevalent stroke in a large cohort of patients with drug refractory
      AF who underwent AF ablation to develop mechanistic insight regarding the risk of
      stroke. METHODS: An institutional cohort of 1063 patients referred for AF
      ablation from 2003 to 2012 was reviewed to identify patients that underwent
      preprocedural cardiac computed tomography (CT). LAA morphology was characterized
      as chicken wing, cactus, windsock, or cauliflower by using previously reported
      methodology. Left atrial size and LAA trabeculations, morphology, orifice
      diameter, and length were compared between patients with prevalent stroke and
      patients without prevalent stroke. RESULTS: Of 678 patients with CT images, 65
      (10%) had prior stroke or transient ischemic attack. In univariate analyses,
      prevalent heart failure (7.7% in cases vs 2.8% in controls; P = .033), smaller
      LAA orifice (2.26 +/- 0.52 cm vs 2.78 +/- 0.71 cm ; P < .001), shorter LAA length
      (5.06 +/- 1.17 cm vs 5.61 +/- 1.17 cm; P < .001), and extensive LAA
      trabeculations (27.7% vs 14.4%; P = .019) were associated with stroke. LAA
      morphologies were unassociated with stroke risk. In multivariable analysis,
      smaller LAA orifice diameter and extensive LAA trabeculations remained
      independently associated with thromboembolic events. CONCLUSIONS: The extent of
      LAA trabeculations and smaller LAA orifice diameter are associated with prevalent
      stroke and may mediate the previously described association of cauliflower LAA
      morphology with stroke.

PMID- 24076445
TI  - A cost-effectiveness analysis of a proactive management strategy for the Sprint
      Fidelis recall: a probabilistic decision analysis model.
AB  - BACKGROUND: The management of the recall is complicated by the competing risks of
      lead failure and complications that can occur with lead revision. Many of these
      patients are currently undergoing an elective generator change--an ideal time to
      consider lead revision. OBJECTIVE: To determine the cost-effectiveness of a
      proactive management strategy for the Sprint Fidelis recall. METHODS: We obtained
      detailed clinical outcomes and costing data from a retrospective analysis of 341
      patients who received the Sprint Fidelis lead in British Columbia, where patients
      younger than 60 years were offered lead extraction when undergoing generator
      replacement. These population-based data were used to construct and populate a
      probabilistic Markov model in which a proactive management strategy was compared
      to a conservative strategy to determine the incremental cost per lead failure
      avoided. RESULTS: In our population, elective lead revisions were half the cost
      of emergent revisions and had a lower complication rate. In the model, the
      incremental cost-effectiveness ratio of proactive lead revision versus a
      recommended monitoring strategy was $12,779 per lead failure avoided. The
      proactive strategy resulted in 21 fewer failures per 100 patients treated and
      reduced the chance of an additional complication from an unexpected surgery.
      CONCLUSIONS: Cost-effectiveness analysis suggests that prospective lead revision
      should be considered when patients with a Sprint Fidelis lead present for pulse
      generator change. Elective revision of the lead is justified even when 25% of the
      population is operated on per year, and in some scenarios, it is both less costly
      and provides a better outcome.

PMID- 24076446
TI  - Differential sequential septal pacing: a simple maneuver to differentiate nodal
      versus extranodal ventriculoatrial conduction.
AB  - BACKGROUND: Distinguishing retrograde nodal conduction from extranodal conduction
      using an accessory pathway (AP) can sometimes be challenging. OBJECTIVE: To
      distinguish nodal from extranodal ventriculoatrial (VA) conduction regardless of
      AP location by proposing a simple method. This method is based on the principle
      that moving the pacing site progressively from the basal region toward the
      entrance of the His-Purkinje system should shorten VA time for nodal but not for
      AP conduction. METHODS: Sixty-seven patients with supraventricular tachycardia
      were prospectively recruited. Quadripolar catheters were placed at the right
      ventricular (RV) apex, right atrium, and His and coronary sinus. The RV septum
      was sequentially paced at 4 sites: (1) basal, (2) high midventricle, (3) low
      midventricle, and (4) apex at a cycle length 100 ms shorter than the resting
      cycle length. The stimulus-to-atrial (SA) interval was measured by using the
      proximal coronary sinus atrial electrogram. RESULTS: Group 1 (n = 33) had nodal
      VA conduction; all patients had typical atrioventricular nodal reentrant
      tachycardia. Group 2 (n = 34) had extranodal VA conduction via an AP: 19 left
      sided, 6 right-sided, and 9 posteroseptal. In group 1, the SA interval decreased
      significantly as pacing site moved closer toward the apex (site 1: 166 +/- 35 ms,
      site 2: 153 +/- 32 ms, site 3: 149 +/- 32 ms, site 4: 154 +/- 33 ms, P < .001,
      respectively, at sites 2-4 compared with site 1). In contrast, in group 2, the SA
      interval increased significantly toward the apex (site 1: 149 +/- 45 ms, site 2:
      158 +/- 43 ms, site 3: 161 +/- 43 ms, and site 4: 163 +/- 40 ms, P < .001,
      respectively, at sites 2-4 compared with site 1). The SA interval at the high
      midventricular site (site 2) - SA interval at the base (site 1) <= 0 ms for nodal
      and > 0 ms for extranodal conduction had optimal sensitivity and specificity
      (nodal: selectivity = 97.0% and specificity = 85.3%; extranodal: selectivity =
      85.3% and specificity = 97.0%). CONCLUSIONS: Differential sequential pacing of
      the RV septum reliably distinguishes retrograde atrioventricular nodal conduction
      from AP conduction.

PMID- 24076447
TI  - Supraventricular tachycardia termination after atrial noncapture: what is the
      mechanism?

PMID- 24076448
TI  - Hemodynamic changes during neural deactivation in awake mice: a measurement by
      laser-Doppler flowmetry in crossed cerebellar diaschisis.
AB  - Crossed cerebellar diaschisis (CCD) caused by contralateral supratentorial
      lesions can be considered a condition of neural deactivation, and hemodynamic
      changes in CCD were investigated with positron emission tomography (PET) in
      humans. In the present study, to investigate the effects of neural deactivation
      on hemodynamics, we developed a new mouse model of CCD, which was caused by
      middle cerebral artery occlusion (MCAO), and measured changes in cerebellar blood
      flow (CbBF), red blood cell (RBC) velocity and concentration due to CCD using
      laser-Doppler flowmetry (LDF) in awake mice. The ratio of the CCD side to the
      unaffected side in the cerebellum for CbBF 1 day after MCAO was decreased by -18%
      compared to baseline (before CCD). The ratio of the CCD side to the unaffected
      side for RBC concentration 1 day after MCAO was decreased by -23% compared to
      baseline. However, no significant changes in the ratio of the CCD side to the
      unaffected side were observed for RBC velocity. The present results indicate that
      the reduction of CbBF induced by neural deactivation was mainly caused by the
      decrease in RBC concentration. In contrast, our previous study showed that RBC
      velocity had a dominant role in the increase in cerebral blood flow (CBF) induced
      by neural activation. If RBC concentration can be considered an indicator of
      cerebral blood volume (CBV), hemodynamic changes due to neural activation and
      deactivation measured by LDF in mice might be in good agreement with human PET
      studies. 

PMID- 24076449
TI  - The effect of high fat diet and saturated fatty acids on insulin signaling in the
      amygdala and hypothalamus of rats.
AB  - Insulin injections into the central nucleus of the amygdala (CeA) inhibit food
      intake but this response is lost quickly on feeding a high fat diet. The purpose
      of the studies described in this manuscript was to identify the potential
      mechanism for the development of this insulin resistance. High fat diets (HFD)
      induced PKCtheta activation and blocked the stimulation of Akt but not mTOR
      phosphorylation in the amygdala in response to CeA insulin injections. Infusions
      of palmitic acid onto the CeA had identical effects to HFD on PKCtheta expression
      and insulin signaling in the amygdala. CeA insulin also induced an increase in
      Akt phosphorylation in the hypothalamus but had no effect on hypothalamic mTOR
      phosphorylation. Feeding HFD but not CeA palmitate infusions reversed the
      hypothalamic Akt signaling response to CeA insulin. These data, which show the
      independence of Akt and mTOR signaling responses to insulin in the amygdala and
      the effect of insulin signaling in the CeA on hypothalamic Akt signaling, suggest
      that the amygdala might also have a significant role in regulating hypothalamic
      responses to dietary fat.

PMID- 24076450
TI  - Applicability of the concept of "platinum sensitivity" to recurrent endometrial
      cancer: the SGSG-012/GOTIC-004/Intergroup study.
AB  - OBJECTIVE: The concept of "platinum sensitivity" has been widely applied in the
      management of recurrent ovarian cancer. This study aimed to evaluate the
      applicability of this concept to recurrent endometrial cancer. PATIENTS AND
      METHODS: In this multicenter retrospective cohort study, the clinical data of
      patients with recurrent endometrial cancer, who had a history of receiving first
      line platinum-based chemotherapy and who received second-line platinum-based
      chemotherapy at the time of recurrence between January 2005 and December 2009
      were reviewed. RESULTS: A total of 262 patients from 30 centers with initial FIGO
      stage classifications of I (29), II (23), III (122), and IV (88) were enrolled.
      In total, 153 endometrioid adenocarcinomas, 34 serous adenocarcinomas, 17 clear
      cell adenocarcinomas, 36 carcinosarcomas, and 22 "other" tumors were documented.
      The response rates for patients with platinum-free intervals of <6 months, 6-11
      months, 12-23 months, and >=24 months were 25%, 38%, 61%, and 65%, respectively.
      The median progression-free survival after second-line platinum-based
      chemotherapy for patients with platinum-free intervals of <12 months and >=12
      months was 4.4 (95% confidence interval (CI)=3.7-5.8) months and 10.3 (95% CI=8.2
      12.6) months, respectively (log-rank P<0.0001), and the median overall survival
      was 13.8 (95% CI=10.6-18.1) months and 40.9 (95% CI=25.3-54.2) months,
      respectively (log-rank P<0.0001). CONCLUSION: Platinum-free interval is a
      predictor of response and survival after second-line platinum-based chemotherapy
      in patients with recurrent endometrial cancer. The concept of "platinum
      sensitivity" could be applicable to recurrent endometrial cancer.

PMID- 24076452
TI  - A class of compartmental models for long-distance tracer transport in plants.
AB  - Studies of long-distance tracer transport in plants result in spatio-temporal
      data sets. Compartmental tracer transport models can be used to quantitatively
      characterize or compare such data sets derived from different experiments.
      Depending on the specific experimental situation it might be necessary to apply
      different models. Here, we present a general class of compartmental tracer
      transport models which allows a systematic comparison of different models
      regarding the quality of fitting to the experimental data. This model class is
      defined by a system of partial differential equations (PDEs) for an arbitrary
      number of parallel compartments with individual transport velocities and numerous
      lateral exchange connections. A large number of model instances with adjustable
      complexity can be derived from this model class by permitting only certain model
      parameters such as flux velocities or exchange rates between compartments to be
      non-zero. Since some of these models are either inconsistent or redundant we
      designed a model filter using combinatory rules in order to keep only valid and
      unique models. A numerical solver for the PDEs was implemented using finite
      volumes and a weighted essentially non-oscillatory (WENO) scheme. Several
      candidate models were fitted to experimental data using a Monte Carlo multi-start
      strategy to approximate the global optimum within a certain parameter space.
      Analysis of exemplary tracer transport experiments on sugar beet, radish and
      maize root resulted in different best models depending on the respective data and
      the required fit quality. 

PMID- 24076451
TI  - The impact of heterogeneous transmission on the establishment and spread of
      antimalarial drug resistance.
AB  - Despite the important insights gained by extending the classical models of
      malaria, other factors, such as immunity, heterogeneous biting, and differential
      patterns of drug use have not been fully explored due to the complexity of
      modeling multiple simultaneous malaria infections competing within a host.
      Understanding these factors is important for understanding how to control the
      spread of drug resistance to artemisinin which is just emerging in Southeast
      Asia. The emergence of resistance plays out at the population level, but is the
      result of competition within individuals for transmission events. Most studies of
      drug resistance evolution have focused on transmission between hosts and ignored
      the role of within-host competition due to the inherent complexity of modeling at
      multiple scales. To embed within-host competition in the model, we used an agent
      based framework that was developed to understand how deviations from the
      classical assumptions of the Ross-MacDonald type models, which have been well
      described and analyzed, impact the dynamics of disease. While structured to be a
      stochastic analog to classical Ross-Macdonald type models, the model is
      nonetheless based on individuals, and thus aspects of within-host competition can
      be explored. We use this framework to explore the role of heterogeneous biting
      and transmission on the establishment and spread of resistance in a population.
      We find that heterogeneous transmission slows the establishment of resistance in
      a population, but once resistance is established, it speeds the spread of
      resistance through the population. These results are due to the skewed
      distribution of biting which makes onward transmission a low probability and
      suggests that targeting the "core" group of individuals that provide the vast
      majority of bites could significantly slow the spread of resistance. 

PMID- 24076453
TI  - Long-term models of oxidative stress and mitochondrial damage in insulin
      resistance progression.
AB  - Insulin resistance, characterized by a reduced cellular response to insulin, is a
      major factor in type 2 diabetes pathogenesis, with a complex etiology consisting
      of a combination of environmental and genetic factors. Oxidative stress, which
      develops through an accumulation of toxic reactive oxygen species generated by
      mitochondria, is believed to contribute to insulin resistance in certain tissues.
      We develop mathematical models of feedback between reactive oxygen species
      production and dysfunction in mitochondria to provide insight into the role of
      oxidative stress in insulin resistance. Our models indicate that oxidative stress
      generated by glucose overload accelerates irreversible mitochondrial dysfunction.
      These models provide a foundation for understanding the long-term progression of
      insulin resistance and type 2 diabetes. 

PMID- 24076454
TI  - Novel polymorphs of the anti-Trypanosoma cruzi drug benznidazole.
AB  - Benznidazole (N-benzyl-2-(2-nitro-1H-imidazol-1-yl)acetamide), is a nitro
      heterocyclic drug used in the treatment of Chagas disease. Despite the fact that
      this drug was released more than 30 years ago, little information about its solid
      state properties is available in the literature. In this study, it was verified
      that this drug exhibits three polymorphs, which were characterized in situ by X
      ray powder diffraction, thermal analysis, hot stage microscopy and infrared
      spectroscopy. The thermodynamic relationships among these polymorphs were also
      discussed.

PMID- 24076455
TI  - Interaction peculiarities of 5,10,15,20-tetrakis(4-N-methylpyridil) tetra iodide
      porphyrin with albumin.
AB  - In present work interactions of bovine serum albumin with 5,10,15,20-tetrakis(4-N
      methylpyridil) tetra iodide porphyrin have been studied by electron absorption
      and fluorescence spectroscopy. The studies were carried out in aqueous media at
      different pH and in water-dimethylformamide mixtures containing up to 0.19 M of
      the organic solvent. It has been demonstrated that the porphyrin forms stable
      complexes with BSA in which the porphyrin is located subdomains IB and IIA. The
      stability constants of the complexes is practically independent of pH.

PMID- 24076456
TI  - Synthesis, spectroscopic characterization and structural investigations of new
      adduct compound of carbazole with picric acid: DNA binding and antimicrobial
      studies.
AB  - Carbazole picrate (CP), a new organic compound has been synthesized,
      characterized by various analytical and spectroscopic technique such as FT-IR, UV
      Vis, (1)H and (13)C NMR spectroscopy. An orthorhombic geometry was proposed based
      on single crystal XRD study. The thermal stability of the crystal was studied by
      using thermo-gravimetric and differential thermal analyses and found that it was
      stable up to 170 degrees C. Further, the newly synthesized title compound was
      tested for its in vitro antibacterial and antifungal activity against various
      bacterial and fungal species. Also, the compound was tested for its binding
      activity with Calf thymus (CT) DNA and the results show a considerable
      interaction between CP and CT-DNA. 

PMID- 24076458
TI  - Molecular modeling and multispectroscopic studies of the interaction of
      mesalamine with bovine serum albumin.
AB  - The interaction of mesalamine (5-aminosalicylic acid (5-ASA)) with bovine serum
      albumin (BSA) was investigated by fluorescence quenching, absorption
      spectroscopy, circular dichroism (CD) techniques, and molecular docking.
      Thermodynamic parameters (DeltaH<0 and DeltaS 0) indicated that the hydrogen bond
      and electrostatic forces played the major role in the binding of 5-ASA to BSA.
      The results of CD and UV-vis spectroscopy showed that the binding of this drug to
      BSA induces some conformational changes in BSA. Displacement experiments
      predicted that the binding of 5-ASA to BSA is located within domain III, Sudlows
      site 2, that these observations were substantiated by molecular docking studies.
      In addition, the docking result shows that the 5-ASA in its anionic form mainly
      interacts with Gln-416 residue through one hydrogen bond between H atom of 5-ASA
      anion and the adjacent O atom of the hydroxyl group of Gln-416. 

PMID- 24076457
TI  - Non-destructive analysis of the conformational differences among feedstock
      sources and their corresponding co-products from bioethanol production with
      molecular spectroscopy.
AB  - The objective of this study was to determine the possibility of using molecular
      spectroscopy with multivariate technique as a fast method to detect the source
      effects among original feedstock sources of wheat and their corresponding co
      products, wheat DDGS, from bioethanol production. Different sources of the
      bioethanol feedstock and their corresponding bioethanol co-products, three
      samples per source, were collected from the same newly-built bioethanol plant
      with current bioethanol processing technology. Multivariate molecular spectral
      analyses were carried out using agglomerative hierarchical cluster analysis
      (AHCA) and principal component analysis (PCA). The molecular spectral data of
      different feedstock sources and their corresponding co-products were compared at
      four different regions of ca. 1800-1725 cm(-1) (carbonyl CO ester, mainly related
      to lipid structure conformation), ca. 1725-1482 cm(-1) (amide I and amide II
      region mainly related to protein structure conformation), ca. 1482-1180 cm(-1)
      (mainly associated with structural carbohydrate) and ca. 1180-800 cm(-1) (mainly
      related to carbohydrates) in complex plant-based system. The results showed that
      the molecular spectroscopy with multivariate technique could reveal the
      structural differences among the bioethanol feedstock sources and among their
      corresponding co-products. The AHCA and PCA analyses were able to distinguish the
      molecular structure differences associated with chemical functional groups among
      the different sources of the feedstock and their corresponding co-products. The
      molecular spectral differences indicated the differences in functional,
      biomolecular and biopolymer groups which were confirmed by wet chemical analysis.
      These biomolecular and biopolymer structural differences were associated with
      chemical and nutrient profiles and nutrient utilization and availability.
      Molecular spectral analyses had the potential to identify molecular structure
      difference among bioethanol feedstock sources and their corresponding co
      products.

PMID- 24076459
TI  - Raman, infrared and near-infrared spectroscopic characterization of the herderite
      hydroxylherderite mineral series.
AB  - Natural single-crystal specimens of the herderite-hydroxylherderite series from
      Brazil, with general formula CaBePO4(F,OH), were investigated by electron
      microprobe, Raman, infrared and near-infrared spectroscopies. The minerals occur
      as secondary products in granitic pegmatites. Herderite and hydroxylherderite
      minerals show extensive solid solution formation. The Raman spectra of
      hydroxylherderite are characterized by bands at around 985 and 998 cm(-1),
      assigned to nu1 symmetric stretching mode of the HOPO3(3-) and PO4(3-) units.
      Raman bands at around 1085, 1128 and 1138 cm(-1) are attributed to both the HOP
      and PO antisymmetric stretching vibrations. The set of Raman bands observed at
      563, 568, 577, 598, 616 and 633 cm(-1) are assigned to the nu4 out of plane
      bending modes of the PO4 and H2PO4 units. The OH Raman stretching vibrations of
      hydroxylherderite were observed ranging from 3626 cm(-1) to 3609 cm(-1). The
      infrared stretching vibrations of hydroxylherderites were observed between 3606
      cm(-1) and 3599 cm(-1). By using a Libowitzky type function, hydrogen bond
      distances based upon the OH stretching bands were calculated. Characteristic NIR
      bands at around 6961 and 7054 cm(-1) were assigned to the first overtone of the
      fundamental, whilst NIR bands at 10,194 and 10,329 cm(-1) are assigned to the
      second overtone of the fundamental OH stretching vibration. Insight into the
      structure of the herderite-hydroxylherderite series is assessed by vibrational
      spectroscopy.

PMID- 24076460
TI  - FT-IR, FT-Raman, UV, NMR spectra, molecular structure, ESP, NBO and HOMO-LUMO
      investigation of 2-methylpyridine 1-oxide: a combined experimental and DFT study.
AB  - In this paper, the equilibrium geometry, bonding features, vibrational
      frequencies, (1)H and (13)C chemical shift values, molecular electrostatic
      potential maps, HOMO-LUMO energies and several thermodynamic parameters of title
      compound in the ground state have been calculated by using the density functional
      method with 6-31G(d,p) and 6-311G(d,p) basis sets. A detailed interpretation of
      the infrared and Raman spectra of 2-methylpyridine 1-oxide was reported.
      Furthermore, natural bond orbitals were performed in this work. The theoretical
      results showed an excellent agreement with the experimental values. 

PMID- 24076461
TI  - Ethnobotanical study of nutri-medicinal plants used for the management of
      HIV/AIDS opportunistic ailments among the local communities of western Uganda.
AB  - ETHNOPHARMACOLOGICAL RELEVANCE: Herbal remedies are a source of therapeutics for
      nearly 80% of the population in Uganda. Poor health facilities and limited access
      to antiretroviral drugs have perpetuated and increased the use of traditional
      medicine especially in rural areas for the treatment of opportunistic ailments of
      HIV/AIDS. To document the traditional uses of nutri-medicinal plants in the
      management of immunocompromised ailments associated with HIV/AIDS. To document
      the parts and growth forms of plants used, methods of preparation and
      administration of the herbal remedies. MATERIALS AND METHODS: The study was
      conducted in Mbarara and Isingiro districts of western Uganda between December
      2010 and May 2011. Ethnobotanical information was collected from 64 respondents
      who were sampled based on recommendations of local elders and administrators.
      Ethnobotanical data on the use of nutri-medicinal plants for traditional
      treatment of HIV/AIDS opportunistic ailments were collected by employing semi
      structured interviews with selected respondents, house hold visits and field
      observations as described by (Martin, 1995a). The respondents were mainly
      traditional medical practitioners who treat patients who are already receiving
      antiretroviral drugs. Fidelity levels of plant species and informant consensus
      factor were determined to show the percentage of informants claiming the use of
      certain plant species for the same major purpose and to analyse people's
      knowledge of plant use. RESULTS: The study revealed 81 plant species most of
      which were herbs (49%). Leaves (71%) were the most frequently used parts in
      remedy preparations which were mainly administered orally (85%). The majority of
      plants (54%) were harvested from wild populations. Hibiscus sabdariffa L.,
      Plumeria obtusa L., and Abutilon guineense (Shumach.) Baker. F and Exell were the
      nutri-medicinal plants that scored the highest Fidelity level values. The
      informant's consensus about usages of plants ranged from 0.75 to 0.80. Plants
      that are presumed to be effective in treating a certain disease have higher
      informant consensus factor (ICF) values. Family Asteraceae accounted for 18% of
      the total species recorded. Thirteen species (16%) of the plants are edible and
      provide nutritional support. CONCLUSION: The study recorded plant species with
      potential to treat ailments associated with immunocompromised people living with
      HIV/AIDS in western Uganda. Such studies can help stimulate confidence in
      traditional medicine and enhance appreciation of herbal medicine among the people
      and to appreciate the value of the plant resources and therefore enhance
      conservation efforts of the plant species. The high consensus means the majority
      of informants agree on the use of plant species and this reflects the
      intercultural relevance and the agreement in the use of the nutri-medicinal
      plants to the people. We recommend the documented plants for further
      Ethnopharmacological studies.

PMID- 24076462
TI  - Enzymatic, antimicrobial and toxicity studies of the aqueous extract of Ananas
      comosus (pineapple) crown leaf.
AB  - ETHNOPHARMACOLOGICAL RELEVANCE: Various parts of the plant pineapple (Ananas
      comosus) are used in traditional medicine worldwide for treatment of a number of
      diseases and disorders. In folk medicine, pineapple leaf extract was used as an
      antimicrobial, vermicide, purgative, emmenagoogue, abortifacient, anti-oedema and
      anti-inflammatory agent. Compared to the fruit and stem extracts of pineapple,
      information about its leaf extract is limited. The potential of pineapple crown
      leaf extract as an ethno-medicine has been evaluated in terms of its enzymatic
      activities related to wound healing, antimicrobial property and toxicity.
      MATERIALS AND METHODS: Major protein components of the extract were revealed by 2
      D gel electrophoresis followed by MS/MS analysis. Zymography, DQ-gelatin assay
      were performed to demonstrate proteolytic, fibrinolytic, gelatinase and
      collagenase activities. DNase and RNase activities were revealed from agarose gel
      electrophoresis. Antimicrobial activity was evaluated spectrophotometrically from
      growth inhibition. Sprague-Dawley rat model was used to measure acute and sub
      acute toxicity of the extract by analyzing blood markers. RESULT: The extract
      contains several proteins that were clustered under native condition. Proteomic
      studies indicated presence of fruit bromelain as major protein constituent of the
      extract. It showed nonspecific protease activity, gelatinolytic, collagenase,
      fibrinolytic, acid and alkaline phosphatase, peroxidase, DNase and RNase
      activities along with considerable anti-microbial property. The leaf extract did
      not induce any toxicity in rats after oral administration of acute and sub-acute
      doses. CONCLUSION: Pineapple leaf extract is nontoxic, contains enzymes related
      to damage tissue repairing, wound healing and possibly prevents secondary
      infections from microbial organisms.

PMID- 24076463
TI  - Carboxymethyl cellulose wafers containing antimicrobials: a modern drug delivery
      system for wound infections.
AB  - Lyophilised wafers have been shown to have potential as a modern dressing for
      mucosal wound healing. The wafer absorbs wound exudates and transforms into a
      gel, thus providing a moist environment which is essential for wound healing. The
      objective of this study was to develop a carboxymethyl cellulose wafer containing
      antimicrobials to promote wound healing and treat wound infection. The pre
      formulation studies began with four polymers, sodium carboxymethyl cellulose
      (NaCMC), methylcellulose (MC), sodium alginate and xanthan gum, but only NaCMC
      and MC were chosen for further investigation. The wafers were characterised by
      physical assessments, solvent loss, microscopic examination, swelling and
      hydration properties, drug content uniformity, drug release and efficacy of
      antimicrobials. Three of the antimicrobials, neomycin trisulphate salt hydrate,
      sulphacetamide sodium and silver nitrate, were selected as model drugs. Among the
      formulations, NaCMC wafer containing neomycin trisulphate exhibited the most
      desirable wound dressing characteristics (i.e., flexibility, sponginess, uniform
      wafer texture, high content drug uniformity) with the highest in vitro drug
      release and the greatest inhibition against both Gram positive and Gram negative
      bacteria. In conclusion, we successfully developed a NaCMC lyophilised wafer
      containing antimicrobials, and this formulation has potential for use in mucosal
      wounds infected with bacteria. 

PMID- 24076464
TI  - In vivo pharmacokinetics, biodistribution and antitumor effect of amphiphilic
      poly(L-amino acids) micelles loaded with a novel all-trans retinoic acid
      derivative.
AB  - Poly(amino acid)s are well-known as biodegradable and environmentally acceptable
      materials. In this study, a series of poly(L-aspartic acid)-b-poly(L
      phenylalanine) (PAA-PPA) compounds with different degrees of polymerization were
      used to prepare copolymer micelles for a poorly water-soluble drug 4-amino-2
      trifluoromethyl-phenyl retinate (ATPR, a novel all-trans retinoic acid
      derivative) and in vivo pharmacokinetics, biodistribution and antitumor efficacy
      of ATPR delivered by PAA-PPA micelles were evaluated. The area under the plasma
      concentration time curve AUC0->infinity of ATPR-loaded PAA20PPA20 micelles was
      2.23 and 1.97 times higher than that of ATPR solution and ATPR CrmEL solution,
      respectively; In addition, the mean residence time (MRT) was increased 1.67 and
      1.97-fold, respectively and the total body clearance (CL) was reduced 2.25 and
      1.98-fold, respectively. The biodistribution study indicated that most of the
      ATPR in the ATPR-M group was distributed in the liver and there was delayed liver
      aggregation compared with the ATPR solution and ATPR CrmEL solution groups.
      Furthermore, the antitumor efficacy of ATPR-loaded PAA20PPA20 micelles was
      demonstrated in in vivo antitumor models involving mice inoculated with the human
      gastric cancer cell line SGC-7901. At the same dose of 7mg/kg, the ATPR-loaded
      micelles group demonstrated a better tumor growth inhibition and induced
      differentiation than the groups given ATPR solution and ATPR CrmEL solution.
      Therefore, the ATPR-loaded PAA-PPA micelles appear to be a potentially useful
      drug delivery system for ATPR and suitable for the chemotherapy of gastric
      cancer.

PMID- 24076465
TI  - Human lung fibroblasts increase CD4(+)CD25(+)Foxp3(+) T cells in co-cultured
      CD4(+) lymphocytes.
AB  - Aim of this study was to evaluate functional modifications induced by human lung
      fibroblasts in co-cultured CD4(+) T lymphocytes. CD4(+) T cells, resting or
      stimulated with ionomycin/PMA for 6h, were co-cultured with fibroblasts isolated
      from pulmonary biopsies, in contact or separated by a semi-permeable membrane.
      The expression of CD25, CTLA-4, TGF-beta, IFNgamma, IL-2, IL-4, IL-10 and Foxp3
      was evaluated by flow cytometric analysis. Fibroblasts induced a significant
      increment in CD25(+) cells in co-cultured activated CD4(+) T lymphocytes
      separated by a membrane. Moreover, fibroblasts treatment with a COX2 inhibitor
      abrogated the increment in CD25(+) cells whereas exogenous PGE2 restored it. The
      CD25(+) subpopulation was characterized by increased presence of Fox-P3, CTLA-4,
      IL-10 and TGF-beta positive cells while IFN-gamma and IL-2 positive cells were
      diminished. Proliferative response of CD4(+) to the anti CD3/CD28-Abs was
      abrogated in CD4(+) co-cultured with fibroblasts thus demonstrating a suppressive
      feature of the expanded CD25(+) subpopulation. 

PMID- 24076466
TI  - A shocking cystory.

PMID- 24076467
TI  - Quality redefined.

PMID- 24076468
TI  - Targeted expression, purification, and cleavage of fusion proteins from inclusion
      bodies in Escherichia coli.
AB  - Today, proteins are typically overexpressed using solubility-enhancing fusion
      tags that allow for affinity chromatographic purification and subsequent removal
      by site-specific protease cleavage. In this review, we present an alternative
      approach to protein production using fusion partners specifically designed to
      accumulate in insoluble inclusion bodies. The strategy is appropriate for the
      mass production of short peptides, intrinsically disordered proteins, and
      proteins that can be efficiently refolded in vitro. There are many fusion protein
      systems now available for insoluble expression: TrpLE, ketosteroid isomerase,
      PurF, and PagP, for example. The ideal fusion partner is effective at directing a
      wide variety of target proteins into inclusion bodies, accumulates in large
      quantities in a highly pure form, and is readily solubilized and purified in
      commonly used denaturants. Fusion partner removal under denaturing conditions is
      biochemically challenging, requiring harsh conditions (e.g., cyanogen bromide in
      70% formic acid) that can result in unwanted protein modifications. Recent
      advances in metal ion-catalyzed peptide bond cleavage allow for more mild
      conditions, and some methods involving nickel or palladium will likely soon
      appear in more biological applications. 

PMID- 24076469
TI  - DHTKD1 is essential for mitochondrial biogenesis and function maintenance.
AB  - Maintaining the functional integrity of mitochondria is crucial for cell
      function, signal transduction and overall cell activities. Mitochondrial
      dysfunctions may alter energy metabolism and in many cases are associated with
      neurological diseases. Recent studies have reported that mutations in
      dehydrogenase E1 and transketolase domain-containing 1 (DHTKD1), a mitochondrial
      protein encoding gene, could cause neurological abnormalities. However, the
      function of DHTKD1 in mitochondria remains unknown. Here, we report a strong
      correlation of DHTKD1 expression level with ATP production, revealing the fact
      that DHTKD1 plays a critical role in energy production in mitochondria. Moreover,
      suppression of DHTKD1 leads to impaired mitochondrial biogenesis and increased
      reactive oxygen species (ROS), thus leading to retarded cell growth and increased
      cell apoptosis. These findings demonstrate that DHTKD1 contributes to
      mitochondrial biogenesis and function maintenance. 

PMID- 24076470
TI  - Imaging natural cognition in action.
AB  - The primary function of the human brain is arguably to optimize the results of
      our motor actions in an ever-changing environment. Our cognitive processes and
      supporting brain dynamics are inherently coupled both to our environment and to
      our physical structure and actions. To investigate human cognition in its most
      natural forms demands imaging of brain activity while participants perform
      naturally motivated actions and interactions within a full three-dimensional
      environment. Transient, distributed brain activity patterns supporting
      spontaneous motor actions, performed in pursuit of naturally motivated goals, may
      involve any or all parts of cortex and must be precisely timed at a speed faster
      than the speed of thought and action. Hemodynamic imaging methods give
      information about brain dynamics on a much slower scale, and established
      techniques for imaging brain dynamics in all modalities forbid participants from
      making natural extensive movements so as to avoid intractable movement-related
      artifacts. To overcome these limitations, we are developing mobile brain/body
      imaging (MoBI) approaches to study natural human cognition. By synchronizing
      lightweight, high-density electroencephalographic (EEG) recording with recordings
      of participant sensory experience, body and eye movements, and other
      physiological measures, we can apply advanced data analysis techniques to the
      recorded signal ensemble. This MoBI approach enables the study of human brain
      dynamics accompanying active human cognition in its most natural forms. Results
      from our studies have provided new insights into the brain dynamics supporting
      natural cognition and can extend theories of human cognition and its evolutionary
      function - to optimize the results of our behavior to meet ever-changing goals,
      challenges, and opportunities. 

PMID- 24076471
TI  - Antidiabetic and antioxidant effects of Annona muricata (Annonaceae), aqueous
      extract on streptozotocin-induced diabetic rats.
AB  - ETHNOPHARMACOLOGICAL RELEVANCE: The leaves of Annona muricata are used in
      Cameroon to manage diabetes and its complications. The aim of this study was to
      evaluate the antidiabetic, antioxidant activities and the potential toxicity of
      aqueous extract of Annona muricata in streptozotocin-induced diabetic rats.
      MATERIAL AND METHODS: Oral administration of Annona muricata aqueous extract
      (100mg/kg or 200mg/kg) was studied in normal and streptozotocin-induced diabetic
      rats. In long term treatment, 2 weeks after streptozotocin-induced diabetic rats,
      animals received plant extract during 28 consecutive days. For a protective
      effect, extract was administered 3 days prior to streptozotocin exposure and
      animals were observed 2 weeks without treatment. RESULTS: The plant extract was
      not effective in normal rats. In diabetic rats, single administration of the
      extract significantly reduced blood glucose levels by 75% and 58.22% respectively
      at the dose of 100mg/kg and 200mg/kg as compared to the initial value. Treatment
      of normal rats 3 days prior to diabetes induction showed that, Annona muricata
      extract has no effect within 72h following STZ injection. However, after 14 days
      post-treatment, the extract at the dose of 100mg/kg significantly reduced blood
      glucose levels as compared with initial value and diabetic control rats.
      Immunohistochemical staining of pancreatic beta-cells of diabetic rats treated
      with the dose of 100mg/kg expressed strong staining for beta-cell compared to
      diabetic control. In a long-term study daily administration of Annona muricata
      aqueous extract for 28 days to diabetic rats, reduced blood glucose levels, serum
      creatinine, MDA, AST, ALT activity, and nitrite levels LDL-cholesterol. Total
      cholesterol, triglycerides, SOD, and CAT activity contents were restored.
      CONCLUSION: These different results show that the antidiabetic activity of Annona
      muricata aqueous extract can be explained by its hypolipidaemic effect, its
      antioxidant and protective action on pancreatic beta-cells, which in turn improve
      glucose metabolism.

PMID- 24076472
TI  - Inhibition of the human neutrophil oxidative metabolism by Baccharis
      dracunculifolia DC (Asteraceae) is influenced by seasonality and the ratio of
      caffeic acid to other phenolic compounds.
AB  - ETHNOPHARMACOLOGICAL RELEVANCE: The great potential of phytotherapic drugs for
      treating and preventing inflammatory diseases mediated by increased neutrophil
      reactive oxygen species (ROS) generation has guided the search for new natural
      products with antioxidant and immunomodulatory properties. Baccharis
      dracunculifolia D.C. (Asteraceae), the main botanical source of Brazilian green
      propolis, is a native plant from Brazil widely used in folk medicine as anti
      inflammatory. This study aims: (a) to determine the influence of seasonality on
      the chemical profile and biological activity of Baccharis dracunculifolia
      (Asteraceae) leaf extracts (BdE); (b) to analyze the correlation between the
      major compounds and the ability of BdE to modulate the superoxide anion and total
      ROS generation by human neutrophils. MATERIALS AND METHODS: The extracts were
      obtained from leaf samples collected monthly during one year. The superoxide
      anion and total ROS generation were assessed by the lucigenin (CL-luc)- and
      luminol (CL-lum)-enhanced chemiluminescence assays. RESULTS: Seasonality
      influenced more the quantitative than the qualitative chemical profile of B.
      dracunculifolia, and affected its biological activity. The major compounds
      identified were caffeic acid, p-coumaric acid, aromadendrin-4'-methyl ether
      (AME), isosakuranetin and artepillin C. The IC50 values obtained for CL-lum and
      CL-luc inhibition by BdE ranged from 8.1-15.8 and 5.8-13.3ugmL(-1), respectively,
      and correlated positively with caffeic acid concentration. CL-luc inhibition
      correlated negatively with the concentration of artepillin C, AME, isosakuranetin
      and total flavonoids. The BdE sample from May/07 inhibited CL-lum and CL-luc the
      most strongly (IC50=8.1 +/- 1.6 and 5.8 +/- 1.0 ug mL(-1), respectively), and
      contained the highest ratio of caffeic acid to the other isolated compounds; so,
      this ratio could be employed as chemical marker for this biological activity of
      B. dracunculifolia. CONCLUSION: The ability of B. dracunculifolia to inhibit the
      neutrophil ROS generation depends more on the type and ratio of phenolic
      compounds and flavonoids than on their high absolute concentrations. Together,
      our results help select the most appropriate plant material for the production of
      phytotherapic drugs to be used in the treatment of inflammatory diseases mediated
      by increased neutrophil activation.

PMID- 24076473
TI  - Analgesic activity of DaChuanXiongFang after intranasal administration and its
      potential active components in vivo.
AB  - ETHNOPHARMACOLOGICAL RELEVANCE: DaChuanXiongFang was a well-known formula
      originated from Jin Dynasty, China. It has been used in both China and Japan to
      treat migraine. In the present study, the analgesic and sedative efficacy of
      DaChuanXiongFang ethanol extract (DCXFEE) after intranasal administration was
      tested and compared with that by intragastric route. MATERIALS AND METHODS: Three
      mice experimental models: acetic acid-induced writhing response test, hot-plate
      latent pain response test and pentobarbital-induced sleep model were used to
      evaluate DCXFEE activity. To further explore the in vivo potential active
      components of DCXFEE that contribute to the difference of activity induced by
      different administration route, ultra performance liquid chromatography-mass
      spectrometer (UPLC-MS) was utilized to analyze components in rat brain after
      given DCXFEE (60 mg/kg). RESULTS: DCXFEE showed analgesic efficacy after
      intranasal administration (15, 30 and 60 mg/kg) in acetic acid-induced writhing
      response in mice. While after intragastric administration, DCXFEE only showed
      analgesic efficacy at high dose (60 mg/kg). Moreover, the analgesic potency was
      weaker after intragastric administration compared with that after intranasal
      administration at the same dose (60 mg/kg). Similar results were obtained in hot
      plate latent pain response test in mice. DCXFEE (60 mg/kg) had no sedative effect
      after intranasal and intragastric administration. No components originated from
      DCXFEE were identified in rat brain 15 min after oral administration. One major
      parent component ligustilide was detected in rat brain after intranasal
      administration. CONCLUSION: These data demonstrate that DCXFEE had faster onset
      of action as well as better analgesic efficacy after intranasal administration
      than that after intragastric administration. DCXFEE has no sedative activity on
      potentiation of pentobarbital-induced sleep in mice given by both routes.
      Ligustilide might represents the potential major bioactive component of DCXFEE
      after intranasal administration and contribute to its analgesic activity in vivo.

PMID- 24076474
TI  - The effect of NADPH-oxidase inhibitor apocynin on cognitive impairment induced by
      moderate lateral fluid percussion injury: role of inflammatory and oxidative
      brain damage.
AB  - Traumatic brain injury (TBI) is a devastating disease that commonly causes
      persistent mental disturbances and cognitive deficits. Although studies have
      indicated that overproduction of free radicals, especially superoxide (O2(-))
      derived from nicotinamide adenine dinucleotide phosphate (NADPH) oxidase is a
      common underlying mechanism of pathophysiology of TBI, little information is
      available regarding the role of apocynin, an NADPH oxidase inhibitor, in
      neurological consequences of TBI. Therefore, the present study evaluated the
      therapeutic potential of apocynin for treatment of inflammatory and oxidative
      damage, in addition to determining its action on neuromotor and memory
      impairments caused by moderate fluid percussion injury in mice (mLFPI).
      Statistical analysis revealed that apocynin (5mg/kg), when injected
      subcutaneously (s.c.) 30min and 24h after injury, had no effect on neuromotor
      deficit and brain edema, however it provided protection against mLFPI-induced
      object recognition memory impairment 7days after neuronal injury. The same
      treatment protected against mLFPI-induced IL-1beta, TNF-alpha, nitric oxide
      metabolite content (NOx) 3 and 24h after neuronal injury. Moreover, apocynin
      treatment reduced oxidative damage (protein carbonyl, lipoperoxidation) and was
      effective against mLFPI-induced Na(+), K(+)-ATPase activity inhibition. The
      present results were accompanied by effective reduction in lesion volume when
      analyzed 7days after neuronal injury. These data suggest that superoxide (O2(-))
      derived from NADPH oxidase can contribute significantly to cognitive impairment,
      and that the post injury treatment with specific NADPH oxidase inhibitors, such
      as apocynin, may provide a new therapeutic approach to the control of
      neurological disabilities induced by TBI. 

PMID- 24076475
TI  - Formation and functions of the corneocyte lipid envelope (CLE).
AB  - Corneocytes in mammalian stratum corneum are surrounded by a monolayer of
      covalently bound omega-OH-ceramides that form the corneocyte (-bound) lipid
      envelope (CLE). We review here the structure, composition, and possible functions
      of this structure, with insights provided by inherited and acquired disorders of
      lipid metabolism. This article is part of a Special Issue entitled The Important
      Role of Lipids in the Epidermis and their Role in the Formation and Maintenance
      of the Cutaneous Barrier. Guest Editors: Kenneth R. Feingold and Peter Elias. 

PMID- 24076477
TI  - Magnetically separable Fe3O4@SiO2@TiO2-Ag microspheres with well-designed
      nanostructure and enhanced photocatalytic activity.
AB  - Major efforts in modern material chemistry are devoted to the design and
      fabrication of nanostructured systems with tunable physical-chemical properties
      for advanced catalytic applications. Here, a novel Fe3O4@SiO2@TiO2-Ag
      nanocomposite has been synthesized and characterized by a series of techniques
      including SEM, TEM, XRD, XPS as well as magnetization measurement and
      subsequently tested for the photocatalytic activities. The well-designed
      nanocomposite exhibits significantly superior activity to that of the commercial
      Degussa P25 thanks to the suppression of electron-hole pairs from recombination
      by Ag nanoparticles, and can be easily recycled by applying an external magnetic
      field while maintaining the catalytic activity without significant decrease even
      after running 10 times. The unique nanostructure makes Fe3O4@SiO2@TiO2-Ag a
      highly efficient, recoverable, stable, and cost-effective photocatalytic system
      offering broad opportunities in the field of catalyst synthesis and application. 

PMID- 24076476
TI  - Effects of alpha-eleostearic acid on asolectin liposomes dynamics: relevance to
      its antioxidant activity.
AB  - In this study, the effect of alpha-eleostearic acid (alpha-ESA) on the lipid
      peroxidation of soybean asolectin (ASO) liposomes was investigated. This effect
      was correlated to changes caused by the fatty acid in the membrane dynamics. The
      influence of alpha-ESA on the dynamic properties of liposomes, such as hydration,
      mobility and order, were followed by horizontal attenuated total reflection
      Fourier transform infrared spectroscopy (HATR-FTIR), nuclear magnetic resonance
      (NMR), differential scanning calorimetry (DSC) and UV-vis techniques. The alpha
      ESA showed an in vitro antioxidant activity against the damage induced by
      hydroxyl radical (OH) in ASO liposomes. The analysis of HATR-FTIR frequency
      shifts and bandwidths and (1)H NMR spin-lattice relaxation times, related to
      specific lipid groups, showed that alpha-ESA causes an ordering effect on the
      polar and interfacial regions of ASO liposomes, which may restrict the OH
      diffusion in the membrane. The DSC enthalpy variation analysis suggested that the
      fatty acid promoted a disordering effect on lipid hydrophobic regions, which may
      facilitate interactions between the reactive specie and alpha-ESA. Turbidity
      results showed that alpha-ESA induces a global disordering effect on ASO
      liposomes, which may be attributed to a change in the lipid geometry and shape.
      Results of this study may allow a more complete view of alpha-ESA antioxidant
      mode of action against OH, considering its influence on the membrane dynamics. 

PMID- 24076478
TI  - Schwertmannite as a new Fenton-like catalyst in the oxidation of phenol by H2O2.
AB  - In this study, schwertmannite was prepared through a hydrothermal method and used
      as a new Fenton-like catalyst in the oxidation of phenol by H2O2. The synthesized
      iron oxide had a formula of Fe8O8(OH)4.5(SO4)1.75 with a weak crystalline
      structure as well as a high specific surface area of 325.52 m(2) g(-1). However,
      schwertmannite has not been used as a Fenton-like catalyst so far, and its
      catalytic mechanism in the oxidation of phenol is still unknown. This study
      confirmed that schwertmannite had a good catalytic activity in the oxidation of
      phenol via a OH radical mechanism. The free radicals could be generated on the
      schwertmannite surface by = Fe(III) species and in bulk solution by dissolved
      Fe(III) over a wide pH range. The synthesized schwertmannite also showed a high
      catalytic ability in the oxidation of phenol in the presence of 0.5M nitrate,
      chloride or sulfate anions at initial pH 5.0, indicating its potential
      application in the treatment of high salinity wastewater. In addition, phenol
      removal percentage could still reach 98% after schwertmannite was successively
      used for 12 cycles, indicating the good reusability of this catalyst, although a
      phase transformation of schwertmannite to goethite was observed.

PMID- 24076479
TI  - Microwave-assisted synthesis, characterization and antibacterial activity of
      Ag/ZnO nanoparticles supported bentonite clay.
AB  - Composites of silver-zinc oxide nanoparticles supported on bentonite clay were
      synthesized by the microwave-assisted synthesis method for use as an
      antibacterial material. Silver nitrate was used as the precursor of silver
      nanoparticles while zinc oxide nanoparticles were commercially sourced. The
      composites were characterized by powder X-ray diffraction (XRD), transmission
      electron microscope (TEM), Fourier transform infrared (FTIR) and BET surface area
      measurements. XRD spectra showed peaks of silver confirming the formation of the
      silver and not of the silver nitrate or any other impurity of the metal.
      Meanwhile TEM confirmed the formation of silver and zinc oxide nanoparticles on
      the clay layers, with particle sizes ranging from 9-30 nm and 15-70 nm,
      respectively. The antibacterial activities of the composites were evaluated
      against Gram negative Escherichia coli bacteria and Gram positive Enterococcus
      faecalis bacteria by the disc diffusion method. Whereas both composites of Ag
      clay and ZnO-clay showed good antibacterial activity against bacteria, a better
      antibacterial activity was observed with Ag/ZnO-clay composite. The results
      therefore reveal that Ag/ZnO-clay composite is a promising bactericide that can
      be used for deactivating microbes in water.

PMID- 24076480
TI  - Effective visible light-active boron and europium co-doped BiVO4 synthesized by
      sol-gel method for photodegradion of methyl orange.
AB  - Eu-B co-doped BiVO4 visible-light-driven photocatalysts have been synthesized
      using the sol-gel method. The resulting materials were characterized by a series
      of joint techniques, including XPS, XRD, SEM, BET, and UV-vis DRS analyses.
      Compared with BiVO4 and B-BiVO4 photocatalysts, the Eu-B-BiVO4 photocatalysts
      exhibited much higher photocatalytic activity for methyl orange (MO) degradation
      under visible light irradiation. The optimal Eu doping content is 0.8 mol%. It
      was revealed that boron and europium were doped into the lattice of BiVO4 and
      this led to more surface oxygen vacancies, high specific surface areas, small
      crystallite size, a narrower band gap and intense light absorbance in the visible
      region. The doped Eu(III) cations can help in the separation of photogenerated
      electrons. The synergistic effects of boron and europium in doped BiVO4 were the
      main reason for improving visible light photocatalytic activity.

PMID- 24076481
TI  - Perfluorooctanoic acid degradation in the presence of Fe(III) under natural
      sunlight.
AB  - Due to the high bond dissociation energy (BDE) of CF bonds (116 kcal/mol),
      perfluorooctanoic acid (PFOA) is a highly recalcitrant pollutant. Herein, we
      demonstrate a novel method to decompose PFOA in the presence of sunlight and
      ferric iron (Fe(III)). Under such conditions, 97.8 +/- 1.7% of 50 MUM PFOA
      decomposed within 28 days into shorter-chain intermediates and fluoride (F(-)),
      with an overall defluorination extent of 12.7 +/- 0.5%. No PFOA was removed under
      visible light, indicating that UV radiation is required for PFOA decomposition.
      Spectroscopic analysis indicates that the decomposition reaction is likely
      initiated by electron-transfer from PFOA to Fe(III), forming Fe(II) and an
      unstable organic carboxyl radical. An alternative mechanism for the formation of
      this organic radical involves hydroxyl radicals, detected by electron
      paramagnetic resonance (EPR). The observation that PFOA can be degraded by
      Fe(III) under solar irradiation provides mechanistic insight into a possibly
      overlooked natural attenuation process. Because Fe(III) is abundant in natural
      waters and sunlight is essentially free, this work represents a potentially
      important step toward the development of simple and inexpensive remediation
      strategies for PFOA-contaminated water.

PMID- 24076482
TI  - Chelant extraction of heavy metals from contaminated soils using new selective
      EDTA derivatives.
AB  - Soil washing is one of the few permanent treatment alternatives for removing
      metal contaminants. Ethylenediaminetetraacetic acid (EDTA) and its salts can
      substantially increase heavy metal removal from contaminated soils and have been
      extensively studied for soil washing. However, EDTA has a poor utilization ratio
      due to its low selectivity resulting from the competition between soil major
      cations and trace metal ions for chelation. The present study evaluated the
      potential for soil washing using EDTA and three of its derivatives: CDTA (trans
      1,2-cyclohexanediaminetetraacetic acid), BDTA (benzyldiaminetetraacetic acid),
      and PDTA (phenyldiaminetetraacetic acid), which contain a cylcohexane ring, a
      benzyl group, and a phenyl group, respectively. Titration results showed that
      PDTA had the highest stability constants for Cu(2+) and Ni(2+) and the highest
      overall selectivity for trace metals over major cations. Equilibrium batch
      experiments were conducted to evaluate the efficacy of the EDTA derivatives at
      extracting Cu(2+), Zn(2+), Ni(2+), Pb(2+), Ca(2+), and Fe(3+) from a contaminated
      soil. At pH 7.0, PDTA extracted 1.5 times more Cu(2+) than did EDTA, but only 75%
      as much Ca(2+). Although CDTA was a strong chelator of heavy metal ions, its
      overall selectivity was lower and comparable to that of EDTA. BDTA was the least
      effective extractant because its stability constants with heavy metals were low.
      PDTA is potentially a practical washing agent for soils contaminated with trace
      metals. 

PMID- 24076483
TI  - Reactivity of NiO for 2,4-D degradation with ozone: XPS studies.
AB  - 2,4-Dichlorophenoxyacetic acid (2,4-D) is usually used as a refractory model
      compound that requires a prolonged reaction time for mineralization. In this
      study, we found that nickel oxide (NiO) significantly improved 2,4-D degradation
      and mineralization in reaction with ozone. Other metal oxides, such as titania,
      silica and alumina, were also tested in this reaction, so that, the
      mineralization degree was almost the same for all of them (ca. 25%), whereas NiO
      showed more than 60% in 1h. These outstanding results led us to study in more
      depth the role of NiO as catalyst in the degradation of 2,4-D. For instance, the
      optimum NiO loading amount was 0.3 g L(-1). The catalytic ozonation showed a high
      stability after three reaction cycles. With the aim of identifying the surface
      species responsible for the high activity of NiO, besides knowing the byproducts
      during the degradation of 2,4-D, XPS and HPLC were mainly used as analytical
      tools. According to the results, the mineralization of 2,4-D was directly
      influenced by the adsorbed chlorate organic compounds and oxalate group onto NiO.
      Therefore, NiO plays a true role as a catalyst forming surface compounds which
      are subsequently decomposed causing an increase in the mineralization efficiency.
      In addition, it was possible to identify several degradation byproducts (2,4
      diclorophenol, glycolic, fumaric, maleic and oxalic acids) that were included in
      a rational reaction pathway. It was proposed that 2,4-D elimination in presence
      of NiO as catalyst is a combination of processes such as: conventional ozonation,
      indirect mechanism (OH) and surface complex formation.

PMID- 24076485
TI  - Adaptive enrichment with subpopulation selection at interim: methodologies,
      applications and design considerations.
AB  - There is a growing interest in pursuing adaptive enrichment for drug development
      because of its potential to achieve the goal of personalized medicine. There are
      many versions of adaptive enrichment proposed across many disease indications.
      Some are exploratory adaptive enrichment and others aim at confirmatory adaptive
      enrichment. In this paper, we give a brief overview on adaptive enrichment and
      the methodologies that are growing in statistical literature. A case example is
      provided to illustrate a regulatory experience that led to drug approval. There
      were two design elements used for adaptation in this case example: population
      adaptation and statistical information adaptation. We articulate the challenges
      in the implementation of a confirmatory adaptive enrichment trial. The challenges
      include logistic aspects on the appropriate choice of study population for
      adaptation and the ability to follow the pre-specified rules for statistical
      information or sample size adaptation. We assess the consistency of treatment
      effect before and after adaptation using the approach laid out in Wang et al.
      (2013). We provide the rationales for what would be an appropriate treatment
      effect estimate for reporting in the drug label. We discuss and articulate design
      considerations for adaptive enrichment among a dual-composite null hypothesis, a
      flexible dual-independent null hypothesis and a rigorous dual-independent null
      hypothesis. 

PMID- 24076486
TI  - Changes in the relationship between volume of consumption and alcohol-related
      problems in Sweden during 1979-2003.
AB  - AIMS: The aim of the study was to investigate (i) whether the strength of the
      relationship between self-reported volume of consumption and alcohol-related
      problems has become weaker in Sweden, and (ii) whether such a change can be
      related to temporal changes in drinking patterns or to changes in the
      distribution of consumption and related problems in the population. METHODS:
      Three cross-sectional general population surveys conducted in Sweden in 1979,
      1995 and 2003 yielded data on 5650 Swedish adults aged 18-69 years. The
      relationship between self-reported volume of consumption and self-reported
      alcohol-related problems was estimated using Poisson regression models. Analyses
      of drinking patterns focused on changes in frequency of drinking, volume per
      occasion and frequency of drinking to intoxication. Lorenz curves were used to
      analyse the distributions of consumption and alcohol-related problems. RESULTS:
      Poisson regression estimates revealed that the relationship between volume of
      consumption and alcohol-related problems became weaker over time; a 10% per cent
      change in self-reported volume of consumption was associated with a smaller per
      cent change in the number of experienced problems in 2003 (5%) compared with 1995
      (6%) and 1979 (7%). This change was not related to a hypothesized general shift
      towards a more southern European style of drinking, as no such tendency was
      found. CONCLUSION: The changed relationship appears to be a reflection of a
      redistribution of consumption and alcohol-related problems in the population,
      such that a larger share of all consumption and related problems occurs among
      light or moderate drinkers in 2003 compared with 1979.

PMID- 24076484
TI  - Sex differences in anxiety and depression: role of testosterone.
AB  - Compelling evidence exists for pervasive sex differences in pathological
      conditions, including anxiety and depressive disorders, with females more than
      twice as likely to be afflicted. Gonadal hormones may be a major factor in this
      disparity, given that women are more likely to experience mood disturbances
      during times of hormonal flux, and testosterone may have protective benefits
      against anxiety and depression. In this review we focus on the effects of
      testosterone in males and females, revealed in both human and animal studies. We
      also present possible neurobiological mechanisms underlying testosterone's mostly
      protective benefits, including the brain regions, neural circuits, and cellular
      and molecular pathways involved. While the precise underlying mechanisms remain
      unclear, both activational and organizational effects of testosterone appear to
      contribute to these effects. Future clinical studies are necessary in order to
      better understand when and how testosterone therapy may be effective in both
      sexes. 

PMID- 24076487
TI  - The effect of dabigatran plasma concentrations and patient characteristics on the
      frequency of ischemic stroke and major bleeding in atrial fibrillation patients:
      the RE-LY Trial (Randomized Evaluation of Long-Term Anticoagulation Therapy).
AB  - OBJECTIVES: The goal of this study was to analyze the impact of dabigatran plasma
      concentrations, patient demographics, and aspirin (ASA) use on frequencies of
      ischemic strokes/systemic emboli and major bleeds in atrial fibrillation
      patients. BACKGROUND: The efficacy and safety of dabigatran etexilate were
      demonstrated in the RE-LY (Randomized Evaluation of Long-Term Anticoagulation
      Therapy) trial, but a therapeutic concentration range has not been defined.
      METHODS: In a pre-specified analysis of RE-LY, plasma concentrations of
      dabigatran were determined in patients treated with dabigatran etexilate 110 mg
      twice daily (bid) or 150 mg bid and correlated with the clinical outcomes of
      ischemic stroke/systemic embolism and major bleeding using univariate and
      multivariate logistic regression and Cox regression models. Patient demographics
      and ASA use were assessed descriptively and as covariates. RESULTS: Plasma
      concentrations were obtained from 9,183 patients, with 112 ischemic
      strokes/systemic emboli (1.3%) and 323 major bleeds (3.8%) recorded. Dabigatran
      levels were dependent on renal function, age, weight, and female sex, but not
      ethnicity, geographic region, ASA use, or clopidogrel use. A multiple logistic
      regression model (c-statistic 0.657, 95% confidence interval [CI]: 0.61 to 0.71)
      showed that the risk of ischemic events was inversely related to trough
      dabigatran concentrations (p = 0.045), with age and previous stroke (both p <
      0.0001) as significant covariates. Multiple logistic regression (c-statistic
      0.715, 95% CI: 0.69 to 0.74) showed major bleeding risk increased with dabigatran
      exposure (p < 0.0001), age (p < 0.0001), ASA use (p < 0.0003), and diabetes (p =
      0.018) as significant covariates. CONCLUSIONS: Ischemic stroke and bleeding
      outcomes were correlated with dabigatran plasma concentrations. Age was the most
      important covariate. Individual benefit-risk might be improved by tailoring
      dabigatran dose after considering selected patient characteristics. (Randomized
      Evaluation of Long Term Anticoagulant Therapy [RE-LY] With Dabigatran Etexilate;
      NCT00262600).

PMID- 24076488
TI  - Reply: Of mice and men: atrial fibrillation in veteran endurance runners.

PMID- 24076489
TI  - Hot topics in tetralogy of Fallot.
AB  - Tetralogy of Fallot (TOF) is the most common cyanotic congenital heart defect. We
      explore "hot topics" to highlight areas of emerging science for clinicians and
      scientists in moving toward a better understanding of the long-term management of
      patients with repaired TOF. From a genetic perspective, the etiology of TOF is
      multifactorial, with a familial recurrence risk of 3%. Cardiac magnetic resonance
      is the gold standard assessment tool based on its superior imaging of the right
      ventricular (RV) outflow tract, pulmonary arteries, aorta, and aortopulmonary
      collaterals, and on its ability to quantify biventricular size and function,
      pulmonary regurgitation (PR), and myocardial viability. Atrial re-entrant
      tachycardia will develop in more than 30% of patients, and high-grade ventricular
      arrhythmias will be seen in about 10% of patients. The overall incidence of
      sudden cardiac death is estimated at 0.2%/yr. Risk stratification, even with
      electrophysiologic testing and cardiac magnetic resonance, remains imperfect.
      Drug therapy has largely been abandoned, and defibrillator placement, despite its
      high risks for complications and inappropriate discharges, is often recommended
      for patients at higher risk. Definitive information about optimal surgical
      strategies for primary repair to preserve RV function, reduce arrhythmia, and
      optimize functional status is lacking. Post-operative lesions are often amenable
      to transcatheter intervention. In selected cases, PR may be treated with
      transcatheter valve insertion. Ongoing surveillance of RV function is a crucial
      component of clinical assessment. Except for resynchronization with biventricular
      pacing, no medical therapies have been shown to be effective after RV dysfunction
      occurs. In patients with significant PR with RV dilation, optimal timing of
      pulmonary valve replacement remains uncertain, although accepted criteria are
      emerging.

PMID- 24076491
TI  - The challenge of voltage channels.

PMID- 24076490
TI  - Building quality indicators to improve care for adults with congenital heart
      disease.
AB  - OBJECTIVES: This study sought to develop quality indicators (QIs) for outpatient
      management of adult congenital heart disease (ACHD) patients. BACKGROUND: There
      are no published QIs to promote quality measurement and improvement for ACHD
      patients. METHODS: Working groups of ACHD experts reviewed published data and
      United States, Canadian, and European guidelines to identify candidate QIs. For
      each QI, we specified a numerator, denominator, period of assessment, and data
      source. We submitted the QIs to a 9-member panel of international ACHD experts.
      The panel rated the QIs for validity and feasibility in 2 rounds on a scale of 1
      to 9 using the RAND/University of California-Los Angeles modified-Delphi method,
      and final QI selection was on the basis of median scores. RESULTS: A total of 62
      QIs were identified regarding appropriateness and timing of clinical management,
      testing, and test interpretation. Each QI was ascertainable from health records.
      After the first round of rating, 29 QIs were accepted, none were rejected, and 33
      were equivocal; on the second round, 55 QIs were accepted. Final QIs included: 8
      for atrial septal defects; 9 for aortic coarctation; 12 for Eisenmenger; 9 for
      Fontan; 9 for D-transposition of the great arteries; and 8 for tetralogy of
      Fallot. CONCLUSIONS: This project resulted in development of the first set of QIs
      for ACHD care based on published data, guidelines, and a modified Delphi process.
      These QIs provide a quality of care assessment tool for 6 ACHD conditions. This
      rigorously designed set of QIs should facilitate measuring and improving the
      quality of care for this growing group of patients.

PMID- 24076492
TI  - Of mice and men: atrial fibrillation in veteran endurance runners.

PMID- 24076493
TI  - Consensus and update on the definition of on-treatment platelet reactivity to
      adenosine diphosphate associated with ischemia and bleeding.
AB  - Dual antiplatelet therapy with aspirin and a P2Y12 receptor blocker is a key
      strategy to reduce platelet reactivity and to prevent thrombotic events in
      patients treated with percutaneous coronary intervention. In an earlier consensus
      document, we proposed cutoff values for high on-treatment platelet reactivity to
      adenosine diphosphate (ADP) associated with post-percutaneous coronary
      intervention ischemic events for various platelet function tests (PFTs). Updated
      American and European practice guidelines have issued a Class IIb recommendation
      for PFT to facilitate the choice of P2Y12 receptor inhibitor in selected high
      risk patients treated with percutaneous coronary intervention, although routine
      testing is not recommended (Class III). Accumulated data from large studies
      underscore the importance of high on-treatment platelet reactivity to ADP as a
      prognostic risk factor. Recent prospective randomized trials of PFT did not
      demonstrate clinical benefit, thus questioning whether treatment modification
      based on the results of current PFT platforms can actually influence outcomes.
      However, there are major limitations associated with these randomized trials. In
      addition, recent data suggest that low on-treatment platelet reactivity to ADP is
      associated with a higher risk of bleeding. Therefore, a therapeutic window
      concept has been proposed for P2Y12 inhibitor therapy. In this updated consensus
      document, we review the available evidence addressing the relation of platelet
      reactivity to thrombotic and bleeding events. In addition, we propose cutoff
      values for high and low on-treatment platelet reactivity to ADP that might be
      used in future investigations of personalized antiplatelet therapy. 

PMID- 24076494
TI  - Reply: The challenge of voltage channels.

PMID- 24076495
TI  - Left atrial appendage occlusion: opportunities and challenges.
AB  - Stroke prevention in patients with atrial fibrillation is a growing clinical
      dilemma as the incidence of the arrhythmia increases and risk profiles worsen.
      Strategies in patients with nonvalvular atrial fibrillation have included
      anticoagulation with a variety of drugs. Knowledge that stroke in this setting
      typically results from thrombus in the left atrial appendage has led to the
      development of mechanical approaches, both catheter-based and surgical, to
      occlude that structure. Such a device, if it were safe and effective, might avoid
      the need for anticoagulation and prevent stroke in the large number of patients
      who are currently not treated with anticoagulants. Regulatory approval has been
      difficult due to trial design challenges, balance of the risk-benefit ratio,
      specific patient populations studied, selection of treatment in the control
      group, and specific endpoints and statistical analyses selected. Accumulating
      data from randomized trials and registries with longer-term follow-up continues
      to support a role for left atrial appendage exclusion from the central
      circulation as an alternative to anticoagulation in carefully-selected patient
      populations. 

PMID- 24076496
TI  - Reply to the editor- amiloride concentrations in clinical practice.

PMID- 24076497
TI  - A comparative numerical study of rotating and stationary RF coils in terms of
      flip angle and specific absorption rate for 7 T MRI.
AB  - While high-field magnetic resonance imaging promises improved image quality and
      faster scan time, it is affected by non-uniform flip angle distributions and
      unsafe specific absorption rate levels within the patient, as a result of the
      complicated radiofrequency (RF) field-tissue interactions. This numerical study
      explored the possibility of using a single mechanically rotating RF coil for RF
      shimming and specific absorption rate management applications at 7 T. In
      particular, this new approach (with three different RF coil element arrangements)
      was compared against both an 8-channel parallel coil array and a birdcage volume
      coil, with and without RF current optimisation. The evaluation was conducted
      using an in-house developed and validated finite-difference time-domain method in
      conjunction with a tissue-equivalent human head model. It was found that, without
      current optimisation, the rotating RF coil method produced a more uniform flip
      angle distribution and a lower maximum global and local specific absorption rate
      compared to the 8-channel parallel coil array and birdcage resonator. In
      addition, due to the large number of degrees of freedom in the form of rotated
      sensitivity profiles, the rotating RF coil approach exhibited good RF shimming
      and specific absorption rate management performance. This suggests that the
      proposed method can be useful in the development of techniques that address
      contemporary RF issues associated with high-field magnetic resonance imaging.

PMID- 24076498
TI  - A barrel-related interneuron in layer 4 of rat somatosensory cortex with a high
      intrabarrel connectivity.
AB  - Synaptic connections between identified fast-spiking (FS), parvalbumin (PV)
      positive interneurons, and excitatory spiny neurons in layer 4 (L4) of the barrel
      cortex were investigated using patch-clamp recordings and simultaneous biocytin
      fillings. Three distinct clusters of FS L4 interneurons were identified based on
      their axonal morphology relative to the barrel column suggesting that these
      neurons do not constitute a homogeneous interneuron population. One L4 FS
      interneuron type had an axonal domain strictly confined to a L4 barrel and was
      therefore named "barrel-confined inhibitory interneuron" (BIn). BIns established
      reliable inhibitory synaptic connections with L4 spiny neurons at a high
      connectivity rate of 67%, of which 69% were reciprocal. Unitary IPSPs at these
      connections had a mean amplitude of 0.9 +/- 0.8 mV with little amplitude
      variation and weak short-term synaptic depression. We found on average 3.7 +/-
      1.3 putative inhibitory synaptic contacts that were not restricted to perisomatic
      areas. In conclusion, we characterized a novel type of barrel cortex interneuron
      in the major thalamo-recipient layer 4 forming dense synaptic networks with L4
      spiny neurons. These networks constitute an efficient and powerful inhibitory
      feedback system, which may serve to rapidly reset the barrel microcircuitry
      following sensory activation. 

PMID- 24076499
TI  - Pathogenesis of highly virulent African swine fever virus in domestic pigs
      exposed via intraoropharyngeal, intranasopharyngeal, and intramuscular
      inoculation, and by direct contact with infected pigs.
AB  - To investigate the pathogenesis of African swine fever virus (ASFV), domestic
      pigs (n=18) were challenged with a range (10(2)-10(6) 50% hemadsorbing doses
      (HAD50)) of the highly virulent ASFV-Malawi strain by inoculation via the
      intraoropharyngeal (IOP), intranasopharyngeal (INP), or intramuscular (IM)
      routes. A subsequent contact challenge experiment was performed in which six IOP
      inoculated donor pigs were allowed to have direct contact (DC) with six naive
      pigs for exposure times that varied from 24 to 72 h. All challenge routes
      resulted in clinical progression and postmortem lesions similar to those
      previously described in experimental and natural infection. The onset of clinical
      signs occurred between 1 and 7 days post inoculation (dpi) and included pyrexia
      with variable progression to obtundation, hematochezia, melena, moribundity and
      death with a duration of 4-11 days. Viremia was first detected between 4 and 5
      dpi in all inoculation groups whereas ASFV shedding from the nasal cavity and
      tonsil was first detected at 3-9 dpi. IM and DC were the most consistent modes of
      infection, with 12/12 (100%) of pigs challenged by these routes becoming
      infected. Several clinical and virological parameters were significantly
      different between IM and DC groups indicating dissimilarity between these modes
      of infection. Amongst the simulated natural routes, INP inoculation resulted in
      the most consistent progression of disease across the widest range of doses
      whilst preserving simulation of natural exposure and therefore may provide a
      superior system for pathogenesis and vaccine efficacy investigation.

PMID- 24076500
TI  - Determining a pre-mining radiological baseline from historic airborne gamma
      surveys: a case study.
AB  - Knowing the baseline level of radioactivity in areas naturally enriched in
      radionuclides is important in the uranium mining context to assess radiation
      doses to humans and the environment both during and after mining. This
      information is particularly useful in rehabilitation planning and developing
      closure criteria for uranium mines as only radiation doses additional to the
      natural background are usually considered 'controllable' for radiation protection
      purposes. In this case study we have tested whether the method of contemporary
      groundtruthing of a historic airborne gamma survey could be used to determine the
      pre-mining radiological conditions at the Ranger mine in northern Australia. The
      airborne gamma survey was flown in 1976 before mining started and groundtruthed
      using ground gamma dose rate measurements made between 2007 and 2009 at an
      undisturbed area naturally enriched in uranium (Anomaly 2) located nearby the
      Ranger mine. Measurements of (226)Ra soil activity concentration and (222)Rn
      exhalation flux density at Anomaly 2 were made concurrent with the ground gamma
      dose rate measurements. Algorithms were developed to upscale the ground gamma
      data to the same spatial resolution as the historic airborne gamma survey data
      using a geographic information system, allowing comparison of the datasets.
      Linear correlation models were developed to estimate the pre-mining gamma dose
      rates, (226)Ra soil activity concentrations, and (222)Rn exhalation flux
      densities at selected areas in the greater Ranger region. The modelled levels
      agreed with measurements made at the Ranger Orebodies 1 and 3 before mining
      started, and at environmental sites in the region. The conclusion is that our
      approach can be used to determine baseline radiation levels, and provide a
      benchmark for rehabilitation of uranium mines or industrial sites where
      historical airborne gamma survey data are available and an undisturbed
      radiological analogue exists to groundtruth the data. 

PMID- 24076501
TI  - Diatom community response to climate variability over the past 37,000 years in
      the sub-tropics of the Southern Hemisphere.
AB  - Climate change is impacting global surface water resources, increasing the need
      for a deeper understanding of the interaction between climate and biological
      diversity. This is particularly the case in the Southern Hemisphere sub-tropics,
      where little information exists on the aquatic biota response to climate
      variations. Palaeolimnological techniques, in particular the use of diatoms, are
      well established and can significantly contribute to the understanding of
      climatic variability and the impacts that change in climate have on aquatic
      ecosystems. A sediment core from Lake McKenzie, Fraser Island (Australia), was
      used to investigate interactions between climate influences and aquatic
      ecosystems. This study utilises a combination of proxies including biological
      (diatom), geochemical and chronological techniques to investigate long-term
      aquatic changes within the perched-dune lake. A combination of (210)Pb and AMS
      (14)C dates showed that the retrieved sediment represented a history of ca.
      37,000 cal.yBP. The sedimentation rate in Lake McKenzie is very low, ranging on
      average from 0.11 mm to 0.26 mm per year. A sediment hiatus was observed between
      ca. 18,300 and 14,000 cal.yBP suggesting a period of dry conditions at the site.
      The diatom record shows little variability over the period of record, with
      benthic, freshwater acidic tolerant species dominating. Relative abundance of
      planktonic species and geochemical results indicates a period of increased water
      depth and lake productivity in the early Holocene and a gradual decrease in
      effective precipitation throughout the Holocene. Results from this study not only
      support earlier work conducted on Fraser Island using pollen reconstructions but
      also demonstrate that diatom community diversity has been relatively consistent
      throughout the Holocene and late Pleistocene with only minor cyclical fluctuation
      evident. This record is consistent with the few other aquatic palaeoecological
      records from the Southern Hemisphere sub-tropics.

PMID- 24076502
TI  - Transfer of antibiotic resistance plasmids in pure and activated sludge cultures
      in the presence of environmentally representative micro-contaminant
      concentrations.
AB  - The presence of antibiotics in the natural environment has been a growing issue.
      This presence could also account for the influence that affects microorganisms in
      such a way that they develop resistance against these antibiotics. The aim of
      this study was to evaluate whether the antibiotic resistant gene (ARG) plasmid
      transfer can be facilitated by the impact of 1) environmentally representative
      micro-contaminant concentrations in ppb (part per billion) levels and 2) donor
      recipient microbial complexity (pure vs. mixed). For this purpose, the multidrug
      resistant plasmid, pB10, and Escherichia coli DH5alpha were used as a model
      plasmid and a model donor, respectively. Based on conjugation experiments with
      pure (Pseudomonas aeruginosa PAKexoT) and mixed (activated sludge) cultures as
      recipients, increased relative plasmid transfer frequencies were observed at ppb
      (MUg/L) levels of tetracycline and sulfamethoxazole micro-contaminant exposure.
      When sludge, a more complex community, was used as a recipient, the increases of
      the plasmid transfer rate were always statistically significant but not always in
      P. aeruginosa. The low concentration (10 ppb) of tetracycline exposure led to the
      pB10 transfer to enteric bacteria, which are clinically important pathogens.

PMID- 24076503
TI  - Comparison of particulate matter dose and acute heart rate variability response
      in cyclists, pedestrians, bus and train passengers.
AB  - Exposure to airborne particulate matter (PM) has been linked to cardiovascular
      morbidity and mortality. Heart rate variability (HRV) is a measure of the change
      in cardiac autonomic function, and consistent links between PM exposure and
      decreased HRV have been documented in studies. This study quantitatively assesses
      the acute relative variation of HRV with predicted PM dose in the lungs of
      commuters. Personal PM exposure, HR and HRV were monitored in 32 young healthy
      cyclists, pedestrians, bus and train passengers. Inhaled and lung deposited PM
      doses were determined using a numerical model of the human respiratory tract
      which accounted for varying ventilation rates between subjects and during
      commutes. Linear mixed models were used to examine air pollution dose and HRV
      response relationships in 122 commutes sampled. Elevated PM2.5 and PM10 inhaled
      and lung deposited doses were significantly (p<0.05) associated with decreased
      HRV indices. Percent declines in SDNN (standard deviation of normal RR intervals)
      relative to resting, due to an inter-quartile range increase in PM10 lung
      deposited dose were stronger in cyclists (-6.4%, 95% CI: -11.7, -1.3) and
      pedestrians (-5.8%, 95% CI: -11.3, -0.5), in comparison to bus (-3.2%, 95% CI: 
      6.4, -0.1) and train (-1.8%, -7.5, 3.8) passengers. A similar trend was observed
      in the case of PM2.5 lung deposited dose and results for rMSSD (the square root
      of the squared differences of successive normal RR intervals) followed similar
      trends to SDNN. Inhaled and lung deposited doses accounting for varying
      ventilation rates between modes, individuals and during commutes have been
      neglected in other studies relating PM to HRV. The findings here indicate that
      exercise whilst commuting has an influence on inhaled PM and PM lung deposited
      dose, and these were significantly associated with acute declines in HRV,
      especially in pedestrians and cyclists. 

PMID- 24076504
TI  - Evaluation of impact of shale gas operations in the Barnett Shale region on
      volatile organic compounds in air and potential human health risks.
AB  - Shale gas exploration and production (E&P) has experienced substantial growth
      across the U.S. over the last decade. The Barnett Shale, in north-central Texas,
      contains one of the largest, most active onshore gas fields in North America,
      stretching across 5000 square miles and having an estimated 15,870 producing
      wells as of 2011. Given that these operations may occur in relatively close
      proximity to populated/urban areas, concerns have been expressed about potential
      impacts on human health. In response to these concerns, the Texas Commission on
      Environmental Quality established an extensive air monitoring network in the
      region. This network provides a unique data set for evaluating the potential
      impact of shale gas E&P activities on human health. As such, the objective of
      this study was to evaluate community-wide exposures to volatile organic compounds
      (VOCs) in the Barnett Shale region. In this current study, more than 4.6 million
      data points (representing data from seven monitors at six locations, up to 105
      VOCs/monitor, and periods of record dating back to 2000) were evaluated. Measured
      air concentrations were compared to federal and state health-based air comparison
      values (HBACVs) to assess potential acute and chronic health effects. None of the
      measured VOC concentrations exceeded applicable acute HBACVs. Only one chemical
      (1,2-dibromoethane) exceeded its applicable chronic HBACV, but it is not known to
      be associated with shale gas production activities. Annual average concentrations
      were also evaluated in deterministic and probabilistic risk assessments and all
      risks/hazards were below levels of concern. The analyses demonstrate that, for
      the extensive number of VOCs measured, shale gas production activities have not
      resulted in community-wide exposures to those VOCs at levels that would pose a
      health concern. With the high density of active wells in this region, these
      findings may be useful for understanding potential health risks in other shale
      play regions.

PMID- 24076505
TI  - A review of soil heavy metal pollution from mines in China: pollution and health
      risk assessment.
AB  - Heavy metal pollution has pervaded many parts of the world, especially developing
      countries such as China. This review summarizes available data in the literature
      (2005-2012) on heavy metal polluted soils originating from mining areas in China.
      Based on these obtained data, this paper then evaluates the soil pollution levels
      of these collected mines and quantifies the risks these pollutants pose to human
      health. To assess these potential threat levels, the geoaccumulation index was
      applied, along with the US Environmental Protection Agency (USEPA) recommended
      method for health risk assessment. The results demonstrate not only the severity
      of heavy metal pollution from the examined mines, but also the high carcinogenic
      and non-carcinogenic risks that soil heavy metal pollution poses to the public,
      especially to children and those living in the vicinity of heavily polluted
      mining areas. In order to provide key management targets for relevant government
      agencies, based on the results of the pollution and health risk assessments, Cd,
      Pb, Cu, Zn, Hg, As, and Ni are selected as the priority control heavy metals;
      tungsten, manganese, lead-zinc, and antimony mines are selected as the priority
      control mine categories; and southern provinces and Liaoning province are
      selected as the priority control provinces. This review, therefore, provides a
      comprehensive assessment of soil heavy metal pollution derived from mines in
      China, while identifying policy recommendations for pollution mitigation and
      environmental management of these mines. 

PMID- 24076506
TI  - Analysis of U.S. soil lead (Pb) studies from 1970 to 2012.
AB  - Although lead (Pb) emissions to the air have substantially decreased in the
      United States since the phase-out of leaded gasoline by 1995, amounts of lead in
      some soils remain elevated. Lead concentrations in residential and recreational
      soils are of concern because health effects have been associated with Pb
      exposure. Elevated soil Pb is especially harmful to young children due to their
      higher likelihood of soil ingestion. The purpose of this study is to create a
      comprehensive compilation of U.S. soil Pb data published from 1970 through 2012
      as well as to analyze the collected data to reveal spatial and/or temporal soil
      Pb trends in the U.S. over the past 40 years. A total of 84 soil Pb studies
      across 62 U.S. cities were evaluated. Median soil Pb values from the studies were
      analyzed with respect to year of sampling, residential location type (e.g.,
      urban, suburban), and population density. In aggregate, there was no
      statistically significant correlation between year and median soil Pb; however,
      within single cities, soil Pb generally declined over time. Our analysis shows
      that soil Pb quantities in city centers were generally highest and declined
      towards the suburbs and exurbs of the city. In addition, there was a
      statistically significant, positive relationship between median soil Pb and
      population density. In general, the trends examined here align with previously
      reported conclusions that soil Pb levels are higher in larger urban areas and Pb
      tends to remain in soil for long periods of time.

PMID- 24076507
TI  - Formulated minimal-length synthetic small hairpin RNAs are potent inhibitors of
      hepatitis C virus in mice with humanized livers.
AB  - Short synthetic hairpin RNAs (sshRNAs) (SG220 and SG273) that target the internal
      ribosome entry site of the hepatitis C virus (HCV) were formulated into lipid
      nanoparticles and administered intravenously to HCV-infected urokinase
      plasminogen activator-severe combined immunodeficient mice with livers
      repopulated with human hepatocytes (humanized livers). Weekly administration of
      2.5 mg/kg of each sshRNA for 2 weeks resulted in a maximal mean reduction in
      viral load of 2.5 log10 from baseline. The viral load remained reduced by more
      than 90% at 14 days after the last dose was given. The sshRNAs were well
      tolerated and did not significantly increase liver enzyme levels. These findings
      indicate the in vivo efficacy of a synthetic RNA inhibitor against the HCV genome
      in reducing HCV infection.

PMID- 24076508
TI  - Temporal relation discovery between events and temporal expressions identified in
      clinical narrative.
AB  - The automatic detection of temporal relations between events in electronic
      medical records has the potential to greatly augment the value of such records
      for understanding disease progression and patients' responses to treatments. We
      present a three-step methodology for labeling temporal relations using machine
      learning and deterministic rules over an annotated corpus provided by the 2012
      i2b2 Shared Challenge. We first create an expanded training network of relations
      by computing the transitive closure over the annotated data; we then apply hand
      written rules and machine learning with a feature set that casts a wide net
      across potentially relevant lexical and syntactic information; finally, we employ
      a voting mechanism to resolve global contradictions between the local predictions
      made by the learned classifier. Results over the testing data illustrate the
      contributions of initial prediction and conflict resolution. 

PMID- 24076509
TI  - The evil of sluits: a re-assessment of soil erosion in the Karoo of South Africa
      as portrayed in century-old sources.
AB  - Deep, linear gullies are a common feature of the present landscape of the Karoo
      of South Africa, where they were known locally in the early twentieth century as
      'sluits'. Recent research has shown that many of these features are now stable
      and are no longer significant sediment sources, although they are efficient
      connectors in the landscape. Because most of the gully networks predate the first
      aerial photographs, little is known in the scientific literature about the timing
      of their formation. One secondary source, however, throws interesting light on
      the origin of these features, and the early response by landowners to their
      rehabilitation. The Agricultural Journal of the Cape of Good Hope at the turn of
      the Twentieth Century carried a number of articles by farmers and agricultural
      officers concerning the "evil of sluits". The authors gave accounts of widespread
      incision of valley bottoms by deep, wide gullies. Many of these gullies had been
      in existence for some thirty years but apparently had formed within living
      memory. A number of attempts to prevent further erosion had been put in place at
      the time of writing. This paper presents a review of land degradation,
      specifically gully erosion, and rehabilitation recommendations as given by
      authors writing in this journal. It reflects on the findings in the context of
      assessing land degradation processes through the local knowledge portrayed in the
      journal. 

PMID- 24076510
TI  - Early warning of illegal development for protected areas by integrating cellular
      automata with neural networks.
AB  - Ecological security has become a major issue under fast urbanization in China. As
      the first two cities in this country, Shenzhen and Dongguan issued the ordinance
      of Eco-designated Line of Control (ELC) to "wire" ecologically important areas
      for strict protection in 2005 and 2009 respectively. Early warning systems (EWS)
      are a useful tool for assisting the implementation ELC. In this study, a multi
      model approach is proposed for the early warning of illegal development by
      integrating cellular automata (CA) and artificial neural networks (ANN). The
      objective is to prevent the ecological risks or catastrophe caused by such
      development at an early stage. The integrated model is calibrated by using the
      empirical information from both remote sensing and handheld GPS (global
      positioning systems). The MAR indicator which is the ratio of missing alarms to
      all the warnings is proposed for better assessment of the model performance. It
      is found that the fast urban development has caused significant threats to
      natural-area protection in the study area. The integration of CA, ANN and GPS
      provides a powerful tool for describing and predicting illegal development which
      is in highly non-linear and fragmented forms. The comparison shows that this
      multi-model approach has much better performances than the single-model approach
      for the early warning. Compared with the single models of CA and ANN, this
      integrated multi-model can improve the value of MAR by 65.48% and 5.17%
      respectively. 

PMID- 24076511
TI  - A question of fit: reflections on boundaries, organizations and social-ecological
      systems.
AB  - Although there is acknowledgment that the complexity of social-ecological systems
      governance demands representation from diverse perspectives, there is little
      agreement in the literature on how to cross both fiat (human-demarcated) and bona
      fide (physical) boundaries to address such complexities. As a cohort of
      interdisciplinary scholars, we navigate the boundary between science and practice
      to address the question of fit regarding the role of organizations in
      transcending boundaries. We found there is a need to rectify discrepancies
      between theories about boundaries and theories about organizations. To this end,
      we propose a conceptual framework to analyze transboundary organizations, an
      umbrella term to group the literature on boundary organizations, intermediaries
      and bridging organizations; we introduce this term to illustrate they are not
      mutually exclusive and to facilitate interdisciplinary research. We first examine
      social-ecological systems (SES), a framework intended to improve understandings
      of boundaries and governance. We then continue to unpack the complexity of
      boundaries and organizations, specifically through important transboundary
      concepts such as scale and organizational learning. This helps frame our
      examination of the literature on: 1) boundary organizations; 2) bridging
      organizations (third-party entities); and 3) intermediaries (distinguished by
      their position between other actors). Our review identifies a number of
      discrepancies that pertain to the types of boundaries discussed and the roles
      assigned to organizations governing SES. Important characteristics have emerged
      from our review of transboundary organizations including legitimacy, saliency,
      urgency, and credibility. In developing a conceptual framework, we argue that
      transboundary organizations: 1) expand upon the boundary spectrum, 2) incorporate
      transboundary concepts, and 3) hybridize characteristics of boundary, bridging,
      and intermediary organizations. We conclude with a number of considerations for
      transboundary organizations and recommendations for further research. 

PMID- 24076512
TI  - Influence of cadmium on the symbiotic interaction established between peanut
      (Arachis hypogaea L.) and sensitive or tolerant bradyrhizobial strains.
AB  - Heavy metals in soil are known to affect rhizobia-legume interaction reducing not
      only rhizobia viability, but also nitrogen fixation. In this work, we have
      compared the response of the symbiotic interaction established between the peanut
      (Arachis hypogaea L.) and a sensitive (Bradyrhizobium sp. SEMIA6144) or a
      tolerant (Bradyrhizobium sp. NLH25) strain to Cd under exposure to this metal.
      The addition of 10 MUM Cd reduced nodulation and nitrogen content in both
      symbiotic associations, being the interaction established with the sensitive
      strain more affected than that with the tolerant one. Plants inoculated with the
      sensitive strain accumulated more Cd than those inoculated with the tolerant
      strain. Nodules showed an increase in reactive oxygen species (ROS) production
      when exposed to Cd. The histological structure of the nodules exposed to Cd
      revealed a deposit of unknown material on the cortex and a significant reduction
      in the infection zone diameter in both strains, and a greater number of
      uninfected cells in those nodules occupied by the sensitive strain. In
      conclusion, Cd negatively impacts on peanut-bradyrhizobia interaction,
      irrespective of the tolerance of the strains to this metal. However, the
      inoculation of peanut with Bradyrhizobium sp. NLH25 results in a better symbiotic
      interaction suggesting that the tolerance observed in this strain could limit Cd
      accumulation by the plant. 

PMID- 24076513
TI  - Typology and indicators of ecosystem services for marine spatial planning and
      management.
AB  - The ecosystem services concept provides both an analytical and communicative tool
      to identify and quantify the link between human welfare and the environment, and
      thus to evaluate the ramifications of management interventions. Marine spatial
      planning (MSP) and Ecosystem-based Management (EBM) are a form of management
      intervention that has become increasingly popular and important globally. The
      ecosystem service concept is rarely applied in marine planning and management to
      date which we argue is due to the lack of a well-structured, systematic
      classification and assessment of marine ecosystem services. In this paper we not
      only develop such a typology but also provide guidance to select appropriate
      indicators for all relevant ecosystem services. We apply this marine-specific
      ecosystem service typology to MSP and EBM. We thus provide not only a novel
      theoretical construct but also show how the ecosystem services concept can be
      used in marine planning and management. 

PMID- 24076514
TI  - Continuous electricity generation in stacked air cathode microbial fuel cell
      treating domestic wastewater.
AB  - This study examined the continuous performance of air cathode MFC stacks for
      domestic wastewater treatments at two different temperatures (23 +/- 3  degrees C
      and 30 +/- 1  degrees C) and organic loading rates to determine the effects of
      the electrode connection and hydraulic flow mode on the stack performance. The
      power density and process stability were affected significantly by the electrode
      connection type, flow mode, and operating parameters. The parallel electrode
      connection system (in series flow mode) had benefits of COD removal, Coulombic
      efficiency and maximal power density due to the higher stability of the ORP in
      overall cells. The highest power density of 420 mW/m(2) (12.8 W/m(3)) was
      achieved in series flow and parallel connection mode at an organic loading rate
      of 25.6 g COD/L-d (HRT of 0.33 h) under mesophilic conditions, achieving a COD
      removal of 44%. The results highlight the importance of prefermentation process
      in the application of a stacked MFC for an actual wastewater treatment. 

PMID- 24076515
TI  - Microbacterium oxydans, a novel alginate- and laminarin-degrading bacterium for
      the reutilization of brown-seaweed waste.
AB  - There is a growing demand for the efficient treatment of seaweed waste. We
      identified six bacterial strains from the marine environment for the
      reutilization of brown-seaweed waste, and the most potentially useful strain,
      Microbacterium oxydans, was chosen and further investigated. Plate assays
      indicated that this bacterial isolate possessed both alginate lyase and
      laminarinase activities. The optimal inoculum size, pH, temperature and substrate
      concentration for the degradation of brown-seaweed polysaccharides by the isolate
      were as follows: 20% (v v(-1)), pH 6.0, 37  degrees C, and 5 g L(-1) for alginate
      and 20% (v v(-1)), pH 6.0, 30  degrees C, and 10 g L(-1) for laminarin,
      respectively. During 6 d in culture under the optimal conditions, the isolate
      produced 0.17 g L(-1) of reducing sugars from alginate with 11.0 U mL(-1) of
      maximal alginate lyase activity, and 5.11 and 2.88 g L(-1) of reducing sugars and
      glucose from laminarin, respectively. In particular, a fair amount of laminarin
      was degraded to glucose (28.8%) due to the isolate's exolytic laminarinase
      activity. As a result, the reutilization of brown-seaweed waste by this isolate
      appears to be possible for the production of reducing sugars as a valuable
      resource. This is the first study to directly demonstrate the ability of M.
      oxydans to degrade both alginate and laminarin. 

PMID- 24076516
TI  - Degradation of pesticides chlorpyrifos, cypermethrin and chlorothalonil in
      aqueous solution by TiO2 photocatalysis.
AB  - Degradation of pesticides chlorpyrifos, cypermethrin and chlorothalonil in
      aqueous solution by TiO2 photocatalysis under UVA (365 nm) irradiation was
      examined. Enhancement of degradation and improvement in biodegradability index
      (BOD5/COD ratio) by H2O2 addition were also evaluated. UVA irradiation per se
      produced insignificant degradation of the pesticides. In UV/TiO2 photocatalysis
      (TiO2 1.5 g L(-1), pH 6 and 300 min irradiation), COD and TOC removal were 25.95
      and 8.45%, respectively. In UV/TiO2/H2O2 photocatalysis (TiO2 1.5 g L(-1), H2O2
      100 mg L(-1), pH 6 and 300 min irradiation), COD and TOC removal were 53.62 and
      21.54%, respectively and biodegradability index improved to 0.26. Ammonia
      nitrogen (NH3-N) decreased from 22 to 7.8 mg L(-1) and nitrate-nitrogen (NO3(-)
      N) increased from 0.7 to 13.8 mg L(-1) in 300 min, indicating mineralization.
      Photocatalytic degradation followed pseudo-first order kinetics with rate
      constant (k) of 0.0025 and 0.0008 min(-1) for COD and TOC removal, respectively.
      FTIR spectra indicated degradation of the organic bonds of the pesticides.
      UV/TiO2/H2O2 photocatalysis is effective in degradation of pesticides
      chlorpyrifos, cypermethrin and chlorothalonil in aqueous solution. UV/TiO2/H2O2
      photocatalysis may be applied as pretreatment of a chlorpyrifos, cypermethrin and
      chlorothalonil pesticide wastewater at pH 6, for biological treatment. 

PMID- 24076517
TI  - Adsorption of Direct Blue 53 dye from aqueous solutions by multi-walled carbon
      nanotubes and activated carbon.
AB  - Multi-walled carbon nanotubes (MWCNT) and powder activated carbon (PAC) were used
      as adsorbents for adsorption of Direct Blue 53 dye (DB-53) from aqueous
      solutions. The adsorbents were characterised using Raman spectroscopy, N2
      adsorption/desorption isotherms, and scanning and transmission electron
      microscopy. The effects of initial pH, contact time and temperature on adsorption
      capacity of the adsorbents were investigated. At pH 2.0, optimum adsorption of
      the dye was achieved by both adsorbents. Equilibrium contact times of 3 and 4 h
      were achieved by MWCNT and PAC adsorbents, respectively. The general order
      kinetic model provided the best fit of the experimental data compared to pseudo
      first order and pseudo-second order kinetic adsorption models. For DB-53 dye, the
      equilibrium data (298-323 K) were best fitted to the Sips isotherm model. The
      maximum sorption capacity for adsorption of the dye occurred at 323 K, with the
      values of 409.4 and 135.2 mg g(-1) for MWCNT and PAC, respectively. Studies of
      adsorption/desorption were conducted and the results showed that DB-53 loaded
      MWCNT could be regenerated (97.85%) using a mixture 50% acetone + 50% of 3 mol L(
      1) NaOH. Simulated dye house effluents were used to evaluate the application of
      the adsorbents for effluent treatment (removal of 99.87% and 97.00% for MWCNT and
      PAC, respectively, were recorded). 

PMID- 24076518
TI  - Differential expression of human placental neurotrophic factors in preterm and
      term deliveries.
AB  - Neurotrophic factors such as brain derived neurotrophic factor (BDNF) and nerve
      growth factor (NGF) are involved in development of the placenta and fetal brain.
      A series of human and animal studies in our department have shown that
      micronutrients (folic acid, vitamin B12) and omega 3 fatty acids like DHA are all
      interlinked in the one carbon cycle. Any alterations in one carbon components
      will lead to changes in methylation patterns that further affect the gene
      expression at critical periods of development resulting in complications during
      pregnancy. This may further contribute to risk for neurodevelopmental disorders
      in children born preterm. Therefore this study for the first time examines the
      mRNA levels from preterm and term placentae. A total number of 38 women
      delivering preterm (<37 weeks gestation) and 37 women delivering at term (=>37
      weeks gestation) were recruited. The mRNA levels of BDNF and NGF were analyzed by
      real time quantitative polymerase chain reaction. Our results indicate that BDNF
      and NGF mRNA levels were lower in preterm group as compared to term group. There
      was a positive association of placental BDNF and NGF mRNA levels with cord plasma
      BDNF and NGF levels. The differential expression of BDNF and NGF gene in preterm
      placentae may also alter the vascular development in preterm deliveries. Our data
      suggests that the reduced mRNA levels of BDNF and NGF may possibly be a result of
      altered epigenetic mechanisms and may have an implication for altered fetal
      programming in children born preterm. 

PMID- 24076519
TI  - Ion channels, channelopathies, and tooth formation.
AB  - The biological functions of ion channels in tooth development vary according to
      the nature of their gating, the species of ions passing through those gates, the
      number of gates, localization of channels, tissue expressing the channel, and
      interactions between cells and microenvironment. Ion channels feature unique and
      specific ion flux in ameloblasts, odontoblasts, and other tooth-specific cell
      lineages. Both enamel and dentin have active chemical systems orchestrating a
      variety of ion exchanges and demineralization and remineralization processes in a
      stage-dependent manner. An important role for ion channels is to regulate and
      maintain the calcium and pH homeostasis that are critical for proper enamel and
      dentin biomineralization. Specific functions of chloride channels, TRPVs, calcium
      channels, potassium channels, and solute carrier superfamily members in tooth
      formation have been gradually clarified in recent years. Mutations in these ion
      channels or transporters often result in disastrous changes in tooth development.
      The channelopathies of tooth include altered eruption (CLCN7, KCNJ2, TRPV3), root
      dysplasia (CLCN7, KCNJ2), amelogenesis imperfecta (KCNJ1, CFTR, AE2, CACNA1C,
      GJA1), dentin dysplasia (CLCN5), small teeth (CACNA1C, GJA1), tooth agenesis
      (CLCN7), and other impairments. The mechanisms leading to tooth channelopathies
      are primarily related to pH regulation, calcium homeostasis, or other alterations
      of the niche for tooth eruption and development.

PMID- 24076520
TI  - Transdermal flux predictions for selected selective oestrogen receptor modulators
      (SERMs): comparison with experimental results.
AB  - The aim of this work was to evaluate the feasibility of delivering transdermally
      a series of highly lipophilic compounds (log P ~4-7), comprising several
      selective oestrogen receptor modulators and a modified testosterone (danazol).
      The maximum fluxes of the drugs were predicted theoretically using the modified
      Potts & Guy algorithm (to determine the permeability coefficient (kp) from water)
      and the calculated aqueous solubilities. The correction provided by Cleek & Bunge
      took into account the contribution of the viable epidermal barrier to the skin
      permeation of highly lipophilic compounds. Experimental measurements of drug
      fluxes from saturated hydroalcoholic solutions were determined in vitro through
      excised pig skin. Overall, the predicted fluxes were in good general agreement
      (within a factor of 10) with the experimental results. Most of the experimental
      fluxes were greater than those predicted theoretically suggesting that the 70:30
      v/v ethanol-water vehicle employed may have had a modest skin penetration
      enhancement effect. This investigation shows that the transdermal fluxes of
      highly lipophilic compounds can be reasonably predicted from first principles
      provided that the viable epidermis, underlying the stratum corneum, is included
      as a potentially important contributor to the skin's overall barrier function.
      Furthermore, the absolute values of the measured fluxes, when considered in
      parallel with previous clinical studies, indicate that it might be feasible to
      topically deliver a therapeutically useful amount of some of the compounds
      considered to treat cancerous breast tissue.

PMID- 24076521
TI  - Hierarchically assembled DNA origami tubules with reconfigurable chirality.
AB  - The dynamic reconfiguration of a hierarchically assembled tubular structure is
      demonstrated using the DNA origami technique. Short cylindrical DNA origami
      monomers are synthesized and linked into elongated tubules, which can then be
      disassembled via toehold-mediated strand displacement. The disassembled subunits
      are subsequently linked into tubules of a different chirality. The
      reconfiguration is performed with the subunits carrying dumbbell hairpin DNA
      oligonucleotides or gold nanoparticles (AuNPs). The reconfiguration of higher
      order origami structures presented here is useful for constructing dynamic
      nanostructures that exceed the size limit of single DNA origami and may
      facilitate the study of molecular or particle interactions by tuning their
      relative distance and organization. 

PMID- 24076522
TI  - Fast, simultaneous quantification of three novel cardiac drugs in human urine by
      MEPS-UHPLC-MS/MS for therapeutic drug monitoring.
AB  - A sensitive and selective ultra-high performance liquid chromatography coupled to
      tandem mass spectrometry (UHPLC-MS/MS) method was developed for the fast,
      simultaneous quantification of three novel cardiac drugs (aliskiren, prasugrel
      and rivaroxaban) in human urine. Sample preparation was performed with
      microextraction with packed sorbent (MEPS), which is a miniaturization of solid
      phase extraction. The optimal conditions for MEPS extraction were obtained using
      C8 sorbent, small sample volumes and a short time period (about 3min for the
      entire sample preparation step). Chromatographic separation of the selected
      compounds was achieved in less than 1.5min on a Zorbax Rapid Resolution High
      Definition SB-C18 column using isocratic elution with 0.1% formic acid and
      acetonitrile (70:30, v/v) at a flow rate of 0.8mLmin(-1). The detection was
      performed on a triple quadrupole tandem mass spectrometer by multiple reaction
      monitoring via an electrospray ionization source with positive ionization mode.
      The method was fully validated according to the latest recommendations of
      international guidelines. The lower limit of quantification was 5.0pgmL(-1) for
      aliskiren and rivaroxaban and 0.5pgmL(-1) for prasugrel. The intra- and inter-day
      precision was within 7.12% and the accuracy ranged from -7.54% to 4.17%. The mean
      extraction recoveries of the MEPSC8 methodology were found to be 98.3% for
      aliskiren, 100.3% for rivaroxaban and 99.9% for prasugrel. This MEPSC8-UHPLC
      MS/MS method offers a fast, simple and precise way to determine selected novel
      cardiac drugs in human urine that could be applied to therapeutic drug monitoring
      and pharmacokinetic studies. 

PMID- 24076523
TI  - High sensitivity LC-MS/MS method for direct quantification of human parathyroid 1
      34 (teriparatide) in human plasma.
AB  - Teriparatide, the 1-34 fragment of human parathyroid hormone, is used to treat
      osteoporosis patients with a high risk of fracture by stimulating new bone
      formation. Routinely teriparatide is quantified using radioimmunoassay however
      the LC-MS/MS described here has the potential to achieve greater accuracy and
      precision, higher specificity, and is readily implemented in routine
      bioanalytical laboratories. Hence a complete method combining effective sample
      prep with appropriate LC separation and selected reaction monitoring (SRM) MS
      detection was developed to selectively separate teriparatide from closely related
      endogenous peptides and to reduce interferences. Samples were concentrated
      without evaporation, minimizing the risk of adsorptive losses. Chromatography was
      performed on a sub 2MUm particle charged surface hybrid column, which provided
      significantly higher peak capacity than a traditional C18 column when formic acid
      was used as the mobile phase modifier. Total LC cycle time was 6min. An LOD of
      15pg/mL (3.6fmol/mL) from 200MUL of human plasma was readily achieved and
      standard curves were accurate and precise from 15pg/mL to 500pg/mL. Mean QC
      accuracies ranged from 90% to 106%. Mean QC precision was better than 7%. The CV
      of matrix factors across 6 sources of human plasma was 5%. The assay presented
      here is the first LC-MS method which reaches clinically relevant detection limits
      for teriparatide. 

PMID- 24076524
TI  - The application of an LC-MS/MS method in a pharmacokinetic study for the
      determination of the concentration of nifekalant in human plasma.
AB  - In the present study, a simple, rapid, and accurate liquid chromatography-tandem
      mass spectrometry (LC-MS/MS) method for the determination of the concentration of
      Nifekalant in human plasma was developed and validated. The analyte and the
      internal standard were extracted from human plasma using dichloromethane and
      analyzed using an ultra-fast liquid chromatographer (UFLC) coupled to an
      electrospray ionization (ESI) tandem mass spectrometer in the positive mode. The
      chromatographic analysis was performed isocratically on an Inertsil ODS-SP column
      (150mm*4.6mm I.D., 5MUm). The mobile phase was a mixture of 15% 10mM aqueous
      ammonium formate and 85% methanol (the pH was adjusted to 3.5 with formic acid)
      at a flow rate of 0.8mL/min with a split ratio of 1:1 to the ionization source.
      The lower limit of quantification (LLOQ) was 5.05ng/mL, and a linear calibration
      curve was obtained over the concentration range of 5.05 to 3030ng/mL. The intra
      day and inter-day assay variations were less than 9.06%, and the accuracy values
      (relative error) were in the range of -10.95% to 2.27%. The essential
      pharmacokinetic parameters of the intravenously injection of Nifekalant were
      found to be the following: t1/2=1.26+/-0.16h,Cmax=1.943+/-0.411mg/L, and AUC0
      12h=4.600+/-0.756mg/L.h. 

PMID- 24076525
TI  - Anion-exchange purification of recombinant factor IX from cell culture
      supernatant using different chromatography supports.
AB  - Both recombinant and plasma-derived factor IX concentrates are used in
      replacement therapies for the treatment of haemophilia B. In the present work,
      the capture step for a recombinant FIX (rFIX) purification process was
      investigated. Different strong anion-exchange chromatography media (the resins Q
      Sepharose((r)) FF and Fractogel((r)) TMAE, the monolith CIM((r)) QA and the
      membrane adsorber Sartobind((r)) Q) were tested for their rFIX binding capacity
      under dynamic conditions. In these experiments, crude supernatant from CHO cells
      was used, thus in the presence of supernatant contaminants and mimicking process
      conditions. The highest dynamic binding capacity was obtained for the monolith,
      which was then further investigated. To study pseudoaffinity elution of
      functional rFIX with Ca(2+) ions, a design of experiments to evaluate the effects
      of pH, NaCl and CaCl2 on yield and purification factor was carried out. The
      effect of pH was not statistically significant, and a combination of no NaCl and
      45mM CaCl2 yielded a good purification factor combined with a high yield of
      active rFIX. Under these conditions, activity yield of rFIX was higher than the
      mass yield, confirming selective elution of functional, gamma-carboxylated rFIX.
      Scaling-up of this process 8 fold resulted in very similar process performance.
      Monitoring of the undesired activated FIX (FIXa) revealed that the FIXa/FIX ratio
      (1.94%) was higher in the eluate than in the loaded sample, but was still within
      an acceptable range. HCP and DNA clearances were high (1256 and 7182 fold,
      respectively), indicating that the proposed process is adequate for the intended
      rFIX capture step. 

PMID- 24076526
TI  - From the editor.

PMID- 24076527
TI  - Small valve area with low-gradient aortic stenosis: beware the hard hearted.

PMID- 24076528
TI  - The complex nature of discordant severe calcified aortic valve disease grading:
      new insights from combined Doppler echocardiographic and computed tomographic
      study.
AB  - OBJECTIVES: With concomitant Doppler echocardiography and multidetector computed
      tomography (MDCT) measuring aortic valve calcification (AVC) load, this study
      aimed at defining: 1) independent physiologic/structural determinants of aortic
      valve area (AVA)/mean gradient (MG) relationship; 2) AVC thresholds best
      associated with severe aortic stenosis (AS); and 3) whether, in AS with
      discordant MG, severe calcified aortic valve disease is generally detected.
      BACKGROUND: Aortic stenosis with discordant markers of severity, AVA in severe
      range but low MG, is a conundrum, unresolved by outcome studies. METHODS:
      Patients (n = 646) with normal left ventricular ejection fraction AS underwent
      Doppler echocardiography and AVC measurement by MDCT. On the basis of AVA-indexed
      to-body surface area (AVAi) and MG, patients were categorized as concordant
      severity grading (CG) with moderate AS (AVAi >0.6 cm2/m2, MG <40 mm Hg), severe
      AS (AVAi <=0.6 cm2/m2, MG >= 40 mm Hg), discordant-severity-grading (DG) with low
      MG (AVAi <=0.6 cm(2)/m(2), MG <40 mm Hg), or high-MG (AVAi >0.6 cm(2)/m(2), MG
      >=40 mm Hg). RESULTS: The MG (discordant in 29%) was strongly determined by AVA
      and flow but also independently and strongly influenced by AVC-load (p < 0.0001)
      and systemic arterial compliance (p < 0.0001). The AVC-load (median
      [interquartile range]) was similar within patients with DG (low-MG: 1,619 [965 to
      2,528] arbitrary units [AU]; high-MG: 1,736 [1,209 to 2,894] AU; p = 0.49),
      higher than CG-moderate-AS (861 [427 to 1,519] AU; p < 0.0001) but lower than CG
      severe-AS (2,931 [1,924 to 4,292] AU; p < 0.0001). The AVC-load thresholds
      separating severe/moderate AS were defined in CG-AS with normal flow (stroke
      volume-index >35 ml/m(2)). The AVC-load, absolute or indexed, identified severe
      AS accurately (area under the curve >=0.89, sensitivity >=86%, specificity >=79%)
      in men and women. Upon application of these criteria to DG-low MG, at least one
      half of the patients were identified as severe calcified aortic valve disease,
      irrespective of flow. CONCLUSIONS: Among patients with AS, MG is often discordant
      from AVA and is determined by multiple factors, valvular (AVC) and non-valvular
      (arterial compliance) independently of flow. The AVC-load by MDCT, strongly
      associated with AS severity, allows diagnosis of severe calcified aortic valve
      disease. At least one-half of the patients with discordant low gradient present
      with heavy AVC-load reflective of severe calcified aortic valve disease,
      emphasizing the clinical yield of AVC quantification by MDCT to diagnose and
      manage these complex patients.

PMID- 24076529
TI  - Off-pump transapical implantation of artificial neo-chordae to correct mitral
      regurgitation: the TACT Trial (Transapical Artificial Chordae Tendinae) proof of
      concept.
AB  - OBJECTIVES: The goal of this study was to evaluate the safety and performance of
      the NeoChord DS1000 system (NeoChord, Inc., Minneapolis, Minnesota). BACKGROUND:
      There is an increasing interest in transcatheter mitral valve (MV) treatment. The
      NeoChord DS 1000 system enables off-pump beating heart transapical MV repair with
      implantation of artificial neo-chordae. METHODS: Patients with severe mitral
      regurgitation (MR) due to isolated posterior prolapse were included in this TACT
      (Transapical Artificial Chordae Tendinae) trial. All patients were scheduled for
      off-pump transapical implantation of neo-chordae. RESULTS: Thirty patients at 7
      centers were enrolled. Major adverse events included 1 death due to post
      cardiotomy syndrome and concomitant sepsis and 1 minor stroke with the patient
      fully recovered at the 30-day follow-up visit. Additional patients experienced
      procedural major adverse events related to a reoperation or conversion to
      standard of care. Acute procedural success (placement of at least 1 neo-chord and
      reduction of MR from 3+ or 4+ to <=2+) was achieved in 26 patients (86.7%). In 4
      patients neo-chordae were not placed for technical and/or patient-specific
      reasons. These patients underwent intraoperative (3 patients) or post-operative
      (1 patient) standard MV repair. At 30 days, 17 patients maintained an MR grade
      <=2+. Four patients who developed recurrent MR were successfully treated with
      open MV repair during 30-day follow-up. Results improved with experience: durable
      reduction in MR to <=2+ at 30 days was achieved in 5 (33.3%) of the first 15
      patients and 12 (85.7%) of the last 14 patients. CONCLUSIONS: Off-pump
      transapical implantation of artificial chordae to correct MR is technically safe
      and feasible; however, it yields further potential for improvement of efficacy
      and durability. (Safety and Performance Study of the NeoChord Device [TACT];
      NCT01777815).

PMID- 24076530
TI  - Importance of rigorous evaluation in comparative biomarker studies.

PMID- 24076532
TI  - Left atrial volume index: relation to long-term clinical outcome in type 2
      diabetes.
AB  - OBJECTIVES: The study sought to determine the prognostic importance of left
      atrial (LA) dilation in patients with type 2 diabetes mellitus (T2DM) and no
      history of cardiovascular disease (CVD). BACKGROUND: T2DM is associated with the
      development of CVD, and morphological changes in the heart may appear before
      symptoms arise. METHODS: A total of 305 T2DM patients without known CVD referred
      to a diabetes clinic were included consecutively (age 58.6 +/- 11.3 years,
      diabetes duration 2.0 [interquartile range: 0 to 6.0] years). Each patient
      underwent a comprehensive echocardiogram and a myocardial perfusion scintigraphy
      (MPS) at inclusion. Patients were divided according to left atrial volume index
      (LAVi) >=32 ml/m(2). Patients were followed for median of 5.6 (interquartile
      range: 5.1 to 6.1) years for the occurrence of major cardiac events and death.
      RESULTS: LAVi >=32 ml/m(2) was found in 105 patients (34%). During follow-up, 60
      patients (20%) experienced the composite endpoint, of whom 28 (9%) died. Patients
      with LAVi >=32 ml/m(2) had a significantly higher cardiac event rate and death
      rate (p < 0.001 and p = 0.002, respectively). Univariate predictors of the
      composite endpoint were age, hypertension, left ventricular diastolic function,
      E/e'septum-ratio and LAVi >=32 ml/m(2); however, myocardial ischemia on MPS was
      not a predictor. When adjusting for age and hypertension, only LAVi >=32 ml/m(2)
      was a predictor of the composite endpoint (hazard ratio: 1.82 [95% confidence
      interval: 1.08 to 3.07], p = 0.024). CONCLUSIONS: Increased LAVi was an
      independent and incremental predictor of cardiovascular morbidity and mortality
      in T2DM patients with no history of CVD. (Presence of Macrovascular Disease in
      Type 2 Diabetes Mellitus; NCT00298844).

PMID- 24076531
TI  - Head-to-head comparison of 2 myocardial fibrosis biomarkers for long-term heart
      failure risk stratification: ST2 versus galectin-3.
AB  - OBJECTIVES: ST2 and galectin-3 (Gal-3) were compared head-to-head for long-term
      risk stratification in an ambulatory heart failure (HF) population on top of
      other risk factors including N-terminal pro-B-type natriuretic peptide.
      BACKGROUND: ST2 and Gal-3 are promising biomarkers of myocardial fibrosis and
      remodeling in HF. METHODS: This cohort study included 876 patients (median age:
      70 years, median left ventricular ejection fraction: 34%). The 2 biomarkers were
      evaluated relative to conventional assessment (11 risk factors) plus N-terminal
      pro-B-type natriuretic peptide in terms of discrimination, calibration, and
      reclassification analysis. Endpoints were 5-year all-cause and cardiovascular
      mortality, and the combined all-cause death/HF hospitalization. RESULTS: During a
      median follow-up of 4.2 years (5.9 for alive patients), 392 patients died. In
      bivariate analysis, Gal-3 and ST2 were independent variables for all endpoints.
      In multivariate analysis, only ST2 remained independently associated with
      cardiovascular mortality (hazard ratio: 1.27, 95% confidence interval [CI]: 1.05
      to 1.53, p = 0.014). Incorporation of ST2 into a full-adjusted model for all
      cause mortality (including clinical variables and N-terminal pro-B-type
      natriuretic peptide) improved discrimination (C-statistic: 0.77, p = 0.004) and
      calibration, and reclassified significantly better (integrated discrimination
      improvement: 1.5, 95% CI: 0.5 to 2.5, p = 0.003; net reclassification index: 9.4,
      95% CI: 4.8 to 14.1, p < 0.001). Incorporation of Gal-3 showed no significant
      increase in discrimination or reclassification and worse calibration metrics. On
      direct model comparison, ST2 was superior to Gal-3. CONCLUSIONS: Head-to-head
      comparison of fibrosis biomarkers ST2 and Gal-3 in chronic HF revealed
      superiority of ST2 over Gal-3 in risk stratification. The incremental predictive
      contribution of Gal-3 to existing clinical risk factors was trivial.

PMID- 24076533
TI  - Vasectomy: replacing the preoperative outpatient appointment with a DVD.

PMID- 24076534
TI  - Practical advice for avoidance of pain associated with insertion of intrauterine
      contraceptives.
AB  - Few studies in the scientific literature provide clear direction on the
      prevention or management of pain associated with intrauterine contraceptive (IUC)
      placement. Those that have been published have studied small numbers of women and
      fail to provide definitive conclusions. There are also no guidelines available
      detailing recognised standard approaches to this problem. The consensus
      recommendations in this review focus primarily on non-pharmacological and often
      non-evidence-based interventions. This review includes general considerations,
      practical recommendations for both routine and more difficult cases and guidance
      on the optimal choice of instruments. General considerations, including pre
      insertion counselling, the setting for the procedure, the confidence and
      technique of the provider and the interplay between the provider and assistant,
      can influence women's level of anxiety and, in turn, influence their perception
      of pain and their overall experience. Further studies are required to refine the
      optimal strategy for managing pain associated with IUC insertion. 

PMID- 24076535
TI  - An experimental system for controlled exposure of biological samples to
      electrostatic discharges.
AB  - Electrostatic discharges occur naturally as lightning strokes, and artificially
      in light sources and in materials processing. When an electrostatic discharge
      interacts with living matter, the basic physical effects can be accompanied by
      biophysical and biochemical phenomena, including cell excitation,
      electroporation, and electrofusion. To study these phenomena, we developed an
      experimental system that provides easy sample insertion and removal, protection
      from airborne particles, observability during the experiment, accurate discharge
      origin positioning, discharge delivery into the sample either through an electric
      arc with adjustable air gap width or through direct contact, and reliable
      electrical insulation where required. We tested the system by assessing
      irreversible electroporation of Escherichia coli bacteria (15 mm discharge arc,
      100 A peak current, 0.1 MUs zero-to-peak time, 0.2 MUs peak-to-halving time), and
      gene electrotransfer into CHO cells (7 mm discharge arc, 14 A peak current, 0.5
      MUs zero-to-peak time, 1.0 MUs peak-to-halving time). Exposures to natural
      lightning stroke can also be studied with this system, as due to radial current
      dissipation, the conditions achieved by a stroke at a particular distance from
      its entry are also achieved by an artificial discharge with electric current
      downscaled in magnitude, but similar in time course, correspondingly closer to
      its entry.

PMID- 24076536
TI  - Eye-tracking the own-race bias in face recognition: revealing the perceptual and
      socio-cognitive mechanisms.
AB  - Own-race faces are recognised more accurately than other-race faces and may even
      be viewed differently as measured by an eye-tracker (Goldinger, Papesh, & He,
      2009). Alternatively, observer race might direct eye-movements (Blais, Jack,
      Scheepers, Fiset, & Caldara, 2008). Observer differences in eye-movements are
      likely to be based on experience of the physiognomic characteristics that are
      differentially discriminating for Black and White faces. Two experiments are
      reported that employed standard old/new recognition paradigms in which Black and
      White observers viewed Black and White faces with their eye-movements recorded.
      Experiment 1 showed that there were observer race differences in terms of the
      features scanned but observers employed the same strategy across different types
      of faces. Experiment 2 demonstrated that other-race faces could be recognised
      more accurately if participants had their first fixation directed to more
      diagnostic features using fixation crosses. These results are entirely consistent
      with those presented by Blais et al. (2008) and with the perceptual
      interpretation that the own-race bias is due to inappropriate attention allocated
      to the facial features (Hills & Lewis, 2006, 2011). 

PMID- 24076537
TI  - Fading perceptual resemblance: a path for rhesus macaques (Macaca mulatta) to
      conceptual matching?
AB  - Cognitive, comparative, and developmental psychologists have long been intrigued
      by humans' and animals' capacity to respond to abstract relations like sameness
      and difference, because this capacity may underlie crucial aspects of cognition
      like analogical reasoning. Recently, this capacity has been explored in higher
      order, relational matching-to-sample (RMTS) tasks in which humans and animals try
      to complete analogies of sameness and difference between disparate groups of
      items. The authors introduced a new paradigm to this area, by yoking the
      relational-matching cue to a perceptual-matching cue. Then, using established
      algorithms for shape distortion, the perceptual cue was weakened and eliminated.
      Humans' RMTS performance easily transcended the elimination of perceptual
      support. In contrast, RMTS performance by six macaques faltered as they were
      weaned from perceptual support. No macaque showed evidence of mature RMTS
      performance, even given more than 260,000 training trials during which we tried
      to coax a relational-matching performance from them. It is an important species
      difference that macaques show so hesitant a response to conceptual relations when
      humans respond to them so effortlessly. It raises theoretical questions about the
      emergence of this crucial capacity during humans' cognitive evolution and during
      humans' cognitive development. 

PMID- 24076538
TI  - Gene structure and expression of leptin in Chinese perch.
AB  - Leptin is an important hormone involved in regulation of food intake, energy
      expenditure and reproduction in mammals, but its role in acanthomorph fishes
      remains scant. In the present study, we characterized leptin gene structure and
      its tissue expression in Chinese perch (Siniperca chuatsi). In contrast to
      typical leptin gene organization of 3 exons and 2 introns in other vertebrates,
      Chinese perch leptin gene consisted of 2 exons and 1 intron. This is the first
      leptin gene characterized in Perciformes, and is also the first leptin gene
      lacking an intron reported in Perciformes. The unique gene structure, the
      conservation of both cysteines that form the single disulfide bridge in leptin,
      and stable clustering in phylogenetic analyses substantiate the unambiguous
      orthology of mammalian and fish leptins, despite low amino acid identity.
      Polymorphism of leptin gene was examined in wild and cultivated populations of
      Chinese perch by direct sequencing of 120 fish. No SNP was found in leptin gene.
      Leptin mRNA of Chinese perch was highly expressed in liver, and expressed at low
      levels in brain, visceral adipose tissue, intestine, spleen and muscle. 

PMID- 24076539
TI  - Increased hepatic yolk precursor synthesis, secretion and facilitated uptake by
      follicles are involved in the rejuvenation of reproductive performance of molted
      hens (Gallus gallus domesticus).
AB  - Molt, a natural behavior that is initiated at the end of a lay cycle in birds, is
      implicated in the regression of the reproductive system in birds followed by a
      rejuvenation of egg-laying potential. The aim of the present study was to
      evaluate the physiological basis for the apparent rejuvenation of egg production
      that occurs following molting. Eighty-three-week-old Hy-line hens, were obtained
      and subjected to forced molting. Blood and tissue samples were obtained at the
      beginning of molt (at 83 weeks of age), during molt (at 85 weeks of age) and
      postmolt (at 89 weeks of age). The laying performance, egg quality, blood
      parameters and gene expression in the liver and the ovary were investigated
      before, during and after molt. There was an obvious increase in the postmolt
      laying rate from 70% premolt to 93% postmolt. Eggshell thickness, albumin height,
      Haugh unit and egg shape index were all significantly improved after molt. The
      circulating levels of estrogen and progesterone were lower in the postmolt hens,
      whereas the concentrations of luteinizing hormone and follicle stimulating
      hormone were not significantly affected by molt. These results indicate that
      enhanced hepatic yolk precursor synthesis and secretion contribute to increased
      postmolt laying performance. Molt enhanced the sensitivity of sex hormones in F1
      follicles. Augmented gene expression in the ovary was involved in the
      rejuvenation of the reproductive performance of molted hens. These results
      suggest that facilitated yolk-precursor uptake by follicles is involved in the
      rejuvenation of the reproductive performance of molted hens.

PMID- 24076540
TI  - Maximum atropine dose without clinical signs or symptoms.
AB  - PURPOSE: Atropine 1% has been used to slow the progression of myopia; however, it
      has not gained worldwide clinical acceptance because it results in clinically
      significant pupillary mydriasis and accommodative paralysis. Lower concentrations
      of atropine (0.5 to 0.01%) have been reported to be associated with fewer
      symptoms, while still controlling myopia. It is the purpose of this study to find
      the highest concentration of atropine that does not result in significant
      symptoms from pupillary dilation and accommodative paralysis. METHODS: A 3 * 3
      phase I clinical trial paradigm was used in 12 subjects, to determine the maximum
      dosage of atropine which could be prescribed without creating symptoms or
      clinical signs of insufficient accommodation or excessive pupillary dilation.
      Accommodation was measured by pushouts and pupillary dilation by photography.
      Prior to this study, we established the following criteria for comfort: 5D or
      more of residual amplitude of accommodation, less than or equal to a 3 mm
      pupillary difference between the eyes, and a report of minimal symptoms of near
      vision blur or outside photophobia. RESULTS: Our results indicate that atropine
      0.02% is the highest concentration that did not result in clinical symptoms and
      findings associated with higher dosages. Mean pupillary dilation was 3 mm, and
      mean accommodative amplitude was 8 diopters with this concentration. Further,
      reduction of the concentration of atropine from 0.02 to 0.01% did not seem to
      result in a decrease in clinical signs or symptoms associated with atropine.
      CONCLUSIONS: Atropine 0.02% is the highest concentration that does not produce
      significant clinical symptoms from accommodation paresis or pupillary dilation.
      This would be an appropriate starting point in evaluating a low dosage of
      atropine to slow myopic progression.

PMID- 24076541
TI  - Can manipulation of orthokeratology lens parameters modify peripheral refraction?
AB  - PURPOSE: To investigate changes in peripheral refraction, corneal topography, and
      aberrations induced by changes in orthokeratology (OK) lens parameters in myopes.
      METHODS: Subjects were fitted with standard OK lenses that were worn overnight
      for 2 weeks. Peripheral refraction, corneal topography, and corneal surface
      aberrations were measured at baseline and after 14 nights of OK lens wear.
      Subsequent to a 2-week washout period, subjects were refitted with another set of
      lenses where one eye was randomly assigned to wear an OK lens with a smaller
      optic zone diameter (OZD) and the other eye with a steeper peripheral tangent.
      Measurements were taken again at a second baseline and after 14 days of overnight
      wear of the second OK lens set. RESULTS: Standard OK lenses with a 6-mm OZD and
      1/4 peripheral tangent caused significant changes in both peripheral refraction
      and corneal topography. Significant hyperopic shift occurred in the central
      visual field (VF) while a myopic shift was found at 35 degrees in the nasal VF.
      OK induced significant reductions in corneal power at all positions along the
      horizontal corneal chord except at 2.4 mm nasal where there was no significant
      change and at 2.8 mm nasal where there was an increase in corneal refractive
      power. A positive shift in spherical aberration was induced for all investigated
      lens designs except for the 1/2 tangent design when calculated over a 4-mm pupil.
      Reducing OZD and steepening the peripheral tangent did not cause significant
      changes in peripheral refraction or corneal topography profiles across the
      horizontal meridian. CONCLUSIONS: OK lenses caused significant changes in
      peripheral refraction, corneal topography, and corneal surface aberrations.
      Modifying OZD and peripheral tangent made no significant difference to the
      peripheral refraction or corneal topography profile. Attempting to customize
      refraction and topography changes through manipulation of OK lens parameters
      appears to be a difficult task.

PMID- 24076542
TI  - Peripheral defocus with spherical and multifocal soft contact lenses.
AB  - PURPOSE: To describe peripheral defocus when myopic eyes are corrected with
      spherical and center-distance multifocal soft contact lenses while looking at
      distance and near. METHODS: Twenty-five young adults with spherical contact lens
      corrected refractive error of -0.50 to -6.00 D participated. Refractive error of
      each participant's right eye was measured while it wore a spherical soft contact
      lens (Biofinity) and again while it wore a center-distance multifocal soft
      contact lens with a +2.50-D add (Biofinity Multifocal "D"). Measurements were
      made centrally and along the horizontal meridian at +/-20, +/-30, and +/-40
      degrees from the line of sight at distance and near (3.33-D demand). RESULTS: The
      mean (+/-SD) age and spherical equivalent refractive error were 23.8 +/- 1.3
      years and -3.62 +/- 1.56 D, respectively. At distance, the multifocal contact
      lens resulted in significantly more myopic defocus than the spherical contact
      lens at the 40- and 30-degree locations on the nasal retina and at the 20- and 30
      degree locations on the temporal retina (p < 0.0001). When accommodating to a
      near target, peripheral defocus was more myopic with the multifocal lens than
      with the spherical lens (p < 0.0001). When viewing the near target with the
      spherical lens, participants experienced foveal hyperopic defocus and peripheral
      hyperopic defocus at all but one peripheral location. While participants also
      experienced foveal hyperopic defocus with the multifocal when looking at near,
      peripheral defocus was minimal (not significantly different than zero) at several
      locations (i.e., peripheral emmetropia). CONCLUSIONS: The center-distance
      multifocal lens created peripheral myopic defocus when looking at distance. When
      looking at near, the multifocal lens resulted in relatively more myopic (less
      hyperopic) peripheral defocus than the spherical lens. The defocus profiles
      experienced with the multifocal contact lens in this study make it a good
      candidate for studies seeking to examine the effect of peripheral myopic defocus
      on myopia progression in children.

PMID- 24076543
TI  - Corneal shapes of Chinese emmetropes and myopic astigmats aged 10 to 45 years.
AB  - PURPOSE: Myopia and astigmatism are highly prevalent in the Hong Kong Chinese.
      This study aimed to determine the effects of age and myopic astigmatism (MA) on
      the corneal shape factors in the Hong Kong Chinese. METHODS: One hundred subjects
      with compound MA or emmetropia (EM) were recruited from three age groups: 10 to
      15 years (n = 32), 20 to 25 years (n = 37), and 40 to 45 years (n = 31).
      Refractive errors were measured by noncycloplegic subjective refraction. Corneal
      astigmatism and corneal shape factors were measured by the Scheimpflug-based
      Pentacam. The effects of age and refractive errors on the whole corneal shape
      (mean-P) and the semimeridian corneal shapes (semi-Ps) at the nasal, temporal,
      superior, and inferior corneal quadrants (from corneal apex to 3 mm peripheral
      cornea) were analyzed. RESULTS: Age had significant effects on the mean-P and
      semi-Ps (both p < 0.001), with both EM and MA showing less prolate corneal shapes
      in older age groups. Partial correlation analyses adjusted for age showed that
      mean-P and semi-Ps were correlated with multiple refractive-error components
      (Pearson r = -0.30 to -0.78, all p < 0.05), with higher correlations found along
      the horizontal semi-Ps in MA (Pearson r = +0.37 to -0.78, all p < 0.01). Compared
      with EM, MA had more prolate temporal semi-Ps in all the three age groups (p <
      0.05). Strikingly, age and refractive errors also had significant impacts on the
      asymmetry of the corneal shape along the horizontal meridian. CONCLUSIONS:
      Corneal shapes were influenced by age and MA in the Hong Kong Chinese. These
      results highlight the importance of controlling these factors when designing a
      study on corneal shape.

PMID- 24076544
TI  - Bright light induces choroidal thickening in chickens.
AB  - PURPOSE: Bright light is a potent inhibitor of myopia development in animal
      models. Because development of refractive errors has been linked to changes in
      choroidal thickness, we have studied in chickens whether bright light may exert
      its effects on myopia also through changes in choroidal thickness. METHODS: Three
      day-old chickens were exposed to "bright light" (15,000 lux; n = 14) from 10 AM
      to 4 PM but kept under "normal light" (500 lux) during the remaining time of the
      light phase for 5 days (total duration of light phase 8 AM to 6 PM). A control
      group (n = 14) was kept under normal light during the entire light phase.
      Choroidal thickness was measured in alert, hand-held animals with optical
      coherence tomography at 10 AM, 4 PM, and 8 PM every day. RESULTS: Complete data
      sets were available for 12 chicks in bright light group and nine in normal light
      group. The striking inter-individual variability in choroidal thickness
      (coefficient of variance: 23%) made it necessary to normalize changes to the
      individual baseline thickness of the choroid. During the 6 hours of exposure to
      bright light, choroidal thickness decreased by -5.2 +/- 4.0% (mean +/- SEM). By
      contrast, in the group kept under normal light, choroidal thickness increased by
      +15.4 +/- 4.7% (difference between both groups p = 0.003). After an additional 4
      hours, choroidal thickness increased also in the "bright light group" by +17.8 +/
      3.5%, while there was little further change (+0.6 +/- 4.0%) in the "normal light
      group" (difference p = 0.004). Finally, the choroid was thicker in the "bright
      light group" (+7.6 +/- 26.0%) than in the "normal light group" (day 5: -18.6 +/-
      26.9%; difference p = 0.036). CONCLUSIONS: Bright light stimulates choroidal
      thickening in chickens, although the response is smaller than with experimentally
      imposed myopic defocus, and it occurs with some time delay. It nevertheless
      suggests that choroidal thickening is also involved in myopia inhibition by
      bright light.

PMID- 24076547
TI  - Treatment of refractory sclerodermatous chronic graft-versus-host disease with
      intravenous lidocaine infusions.

PMID- 24076549
TI  - Risk factors and organ involvement of chronic GVHD in Japan.
AB  - Few studies have evaluated the risk factors for chronic GVHD and organ
      involvement associated with different graft types, including unrelated cord blood
      (U-CB). We retrospectively studied 4818 adult patients who received their first
      allogeneic transplantation and survived for at least 100 days. The incidence of
      chronic GVHD at 2 years was 37%. The following factors were associated with the
      development of chronic GVHD: female donor/male recipient, CMV-Ab seropositivity,
      matched related peripheral blood grafts vs matched related BM grafts, no in vivo
      T-cell depletion and the occurrence of grade II-IV acute GVHD. Among these
      factors, the association with acute GVHD occurrence was consistently significant
      across donor subtypes. The use of U-CB was not associated with chronic GVHD, but
      was associated with a low incidence of extensive chronic GVHD. Chronic GVHD
      patients who had received U-CB transplants showed less frequent involvement of
      the oral cavity (28% vs 55%), eye (12% vs 26%), liver (20% vs 44%), lung (11% vs
      25%) and joint (0% vs 6%) than those with matched related BM grafts. In
      conclusion, we found that U-CB transplants were associated with a low incidence
      of extensive chronic GVHD and less frequent involvement of the oral cavity, eye,
      liver, lung and joints. 

PMID- 24076550
TI  - 18F-FDG PET/CT for the assessment of gastrointestinal GVHD: results of a pilot
      study.
AB  - This prospective pilot study aimed to evaluate the predictive value of (18)F-FDG
      PET/CT for early diagnosis of acute gastrointestinal GVHD (GI-GVHD). In all, 42
      consecutive patients who received allo-SCT were included. (18)F-FDG PET/CT was
      systematically performed at a median of 28 (range, 24-38) days after allo-SCT.
      (18)F-FDG PET/CT data review was positive in 15 cases (36%) (9 true positive (TP)
      cases and 6 false positive (FP) cases) and negative in 27 cases (64%; 26 true
      negative (TN) cases and 1 false negative (FN) case) at visual analysis.
      Sensitivity, specificity, positive predictive value, negative predictive value
      and accuracy of (18)F-FDG PET/CT for the diagnosis of acute GI-GVHD were,
      respectively, 81%, 90%, 60%, 96% and 83%. There were no significant differences
      of SUVmax values between grade 1-2 GI-GVHD and severe grade 3-4 GI-GVHD. Overall,
      these preliminary findings suggested that the inflammatory activity of the
      gastrointestinal tract associated with acute GI-GVHD could be assessed by (18)F
      FDG PET/CT suggesting that noninvasive (18)F-FDG PET/CT could become a valuable
      examination to be performed shortly before endoscopy to map acute GI-GVHD
      lesions, guide the biopsy sites and choose the appropriate endoscopic procedure,
      especially in those asymptomatic patients with a positive (18)F-FDG PET/CT. 

PMID- 24076548
TI  - Hematopoietic SCT with cryopreserved grafts: adverse reactions after
      transplantation and cryoprotectant removal before infusion.
AB  - Transplantation of hematopoietic stem cells (HSCs) has been successfully
      developed as a part of treatment protocols for a large number of clinical
      indications, and cryopreservation of both autologous and allogeneic sources of
      HSC grafts is increasingly being used to facilitate logistical challenges in
      coordinating the collection, processing, preparation, quality control testing and
      release of the final HSC product with delivery to the patient. Direct infusion of
      cryopreserved cell products into patients has been associated with the
      development of adverse reactions, ranging from relatively mild symptoms to much
      more serious, life-threatening complications, including
      allergic/gastrointestinal/cardiovascular/neurological complications,
      renal/hepatic dysfunctions, and so on. In many cases, the cryoprotective agent
      (CPA) used-which is typically dimethyl sulfoxide (DMSO)-is believed to be the
      main causal agent of these adverse reactions and thus many studies recommend
      depletion of DMSO before cell infusion. In this paper, we will briefly review the
      history of HSC cryopreservation, the side effects reported after transplantation,
      along with advances in strategies for reducing the adverse reactions, including
      methods and devices for removal of DMSO. Strategies to minimize adverse effects
      include medication before and after transplantation, optimizing the infusion
      procedure, reducing the DMSO concentration or using alternative CPAs for
      cryopreservation and removing DMSO before infusion. For DMSO removal, besides the
      traditional and widely applied method of centrifugation, new approaches have been
      explored in the past decade, such as filtration by spinning membrane, stepwise
      dilution-centrifugation using rotating syringe, diffusion-based DMSO extraction
      in microfluidic channels, dialysis and dilution-filtration through hollow-fiber
      dialyzers and some instruments (CytoMate, Sepax S-100, Cobe 2991, microfluidic
      channels, dilution-filtration system, etc.) as well. However, challenges still
      remain: development of the optimal (fast, safe, simple, automated, controllable,
      effective and low cost) methods and devices for CPA removal with minimum cell
      loss and damage remains an unfilled need. 

PMID- 24076551
TI  - Pattern of relapse and progression after autologous SCT as upfront treatment for
      multiple myeloma.
AB  - The achievement of CR is the crucial step for a prolonged PFS and OS after an
      autologous SCT in multiple myeloma (MM). Unfortunately, even with the use of new
      regimens and the current high CR rates, most, if not all, patients will
      ultimately relapse or progress. We analyzed the type of relapse or progression
      (asymptomatic vs symptomatic), clinical features including the presence of
      extramedullary involvement and time to next treatment in 211 patients who
      underwent melphalan-based autologous SCT over an 18-year period at our
      institution. After autologous SCT, serological or asymptomatic
      relapse/progression was observed in about one half of the patients. The treatment
      free interval was significantly longer in patients relapsing from CR than in
      those progressing from PR (P=0.017). Patients with serological
      relapse/progression had a significantly longer OS than those relapsing from
      symptomatic disease (P=0.002). The relapse pattern was similar to the initial
      clinical presentation. Survival after relapse/progression was shorter in those
      patients with a 24-h urine M-protein excretion of at least 200 mg (P=0.048).
      Extramedullary involvement was frequent (24%), being the highest risk in patients
      with extramedullary involvement at diagnosis (P=0.001). 

PMID- 24076546
TI  - Insights into rapid modulation of neuroplasticity by brain estrogens.
AB  - Converging evidence from cellular, electrophysiological, anatomic, and behavioral
      studies suggests that the remodeling of synapse structure and function is a
      critical component of cognition. This modulation of neuroplasticity can be
      achieved through the actions of numerous extracellular signals. Moreover, it is
      thought that it is the integration of different extracellular signals regulation
      of neuroplasticity that greatly influences cognitive function. One group of
      signals that exerts powerful effects on multiple neurologic processes is
      estrogens. Classically, estrogens have been described to exert their effects over
      a period of hours to days. However, there is now increasing evidence that
      estrogens can rapidly influence multiple behaviors, including those that require
      forebrain neural circuitry. Moreover, these effects are found in both sexes.
      Critically, it is now emerging that the modulation of cognition by rapid
      estrogenic signaling is achieved by activation of specific signaling cascades and
      regulation of synapse structure and function, cumulating in the rewiring of
      neural circuits. The importance of understanding the rapid effects of estrogens
      on forebrain function and circuitry is further emphasized as investigations
      continue to consider the potential of estrogenic-based therapies for
      neuropathologies. This review focuses on how estrogens can rapidly influence
      cognition and the emerging mechanisms that underlie these effects. We discuss the
      potential sources and the biosynthesis of estrogens within the brain and the
      consequences of rapid estrogenic-signaling on the remodeling of neural circuits.
      Furthermore, we argue that estrogens act via distinct signaling pathways to
      modulate synapse structure and function in a manner that may vary with cell type,
      developmental stage, and sex. Finally, we present a model in which the
      coordination of rapid estrogenic-signaling and activity-dependent stimuli can
      result in long-lasting changes in neural circuits, contributing to cognition,
      with potential relevance for the development of novel estrogenic-based therapies
      for neurodevelopmental or neurodegenerative disorders. 

PMID- 24076552
TI  - PBSC collection from family donors in Japan: a prospective survey.
AB  - Severe adverse events (SAE) and late hematological malignancies have been
      reported after PBSC donation. No prospective data on incidence and risk factors
      have been available for family donors so far. The Japan Society for Hematopoietic
      Cell Transplantation (JSHCT) introduced therefore in 2000 a mandatory
      registration system. It defined standards for donor eligibility and asked harvest
      centers to report any SAE immediately. All donors were examined at day 30 and
      were to be contacted once each year for a period of 5 years. Acute SAEs within
      day 30 were reported from 47/3264 donations (1.44%) with 14 events considered as
      unexpected and severe (0.58%). No donor died within 30 days. Late SAEs were
      reported from 39/1708 donors (2.3%). The incidence of acute SAEs was
      significantly higher among donors not matching the JSHCT standards (P=0.0023).
      Late hematological malignancies in PBSC donors were not different compared with a
      retrospective cohort of BM donors (N:1/1708 vs N:2/5921; P=0.53). In conclusion,
      acute and late SAEs do occur in PBSC donors at relatively low frequency but risk
      factors can be defined. 

PMID- 24076553
TI  - Angiogenic factors in preeclampsia: potential for diagnosis and treatment.
AB  - PURPOSE OF REVIEW: The review summarizes new observations of key roles for
      circulating angiogenic factors in diagnosing, managing, and treating
      preeclampsia. RECENT FINDINGS: Alterations in circulating angiogenic factors
      (soluble fms-like tyrosine kinase-1 and placental growth factor) in preeclampsia
      correlate with the diagnosis and adverse outcomes, particularly when the disease
      presents prematurely (<34 weeks). Measurement of these angiogenic biomarkers
      further helps differentiate preeclampsia and its complications from other
      disorders that present with similar clinical profiles. A ratio of soluble fms
      like tyrosine kinase-1/placental growth factor greater than 85 appears ideal as
      the cut-off for both diagnosis and prognosis. There is also evidence that
      modulating these factors has therapeutic effects, suggesting a future role for
      angiogenic factors in treatment and prevention of preeclampsia. SUMMARY:
      Circulating angiogenic biomarkers help in diagnostic and prognostic profiling of
      preeclampsia and may facilitate better management of these patients.

PMID- 24076545
TI  - Mu opioids and their receptors: evolution of a concept.
AB  - Opiates are among the oldest medications available to manage a number of medical
      problems. Although pain is the current focus, early use initially focused upon
      the treatment of dysentery. Opium contains high concentrations of both morphine
      and codeine, along with thebaine, which is used in the synthesis of a number of
      semisynthetic opioid analgesics. Thus, it is not surprising that new agents were
      initially based upon the morphine scaffold. The concept of multiple opioid
      receptors was first suggested almost 50 years ago (Martin, 1967), opening the
      possibility of new classes of drugs, but the morphine-like agents have remained
      the mainstay in the medical management of pain. Termed mu, our understanding of
      these morphine-like agents and their receptors has undergone an evolution in
      thinking over the past 35 years. Early pharmacological studies identified three
      major classes of receptors, helped by the discovery of endogenous opioid peptides
      and receptor subtypes-primarily through the synthesis of novel agents. These
      chemical biologic approaches were then eclipsed by the molecular biology
      revolution, which now reveals a complexity of the morphine-like agents and their
      receptors that had not been previously appreciated. 

PMID- 24076554
TI  - Current issues in the management and monitoring of hypertension in chronic kidney
      disease.
AB  - PURPOSE OF REVIEW: This review highlights recent developments in the management
      and monitoring of hypertension in adults with chronic kidney disease (CKD), not
      on dialysis. RECENT FINDINGS: Ambulatory blood pressure (BP) monitoring and self
      measured BP monitoring can classify abnormal BP patterns better than clinic BP
      readings. Self-measured BP monitoring lowers BP and allows tailoring of
      antihypertensive treatment. Dosing of antihypertensive medication at night
      improves nocturnal hypertension. Recent guidelines recommend a BP target less
      than 140/90 mmHg for patients with CKD without proteinuria and less than 130/80
      mmHg for those with proteinuria. Lower salt intake is associated with a greater
      effect of renin-angiotensin-aldosterone system blockage in CKD. Lifestyle
      modification resulting in weight loss reduces BP in individuals with CKD. Of
      overweight or obese CKD patients, 8% report taking weight loss medication, which
      is a potential safety concern. Weight loss from intensive lifestyle modification
      in individuals with diabetes prevents CKD. SUMMARY: Although we have effective
      tools to monitor and lower BP, we still need clinical outcome studies to inform
      BP targets for specific age groups, types of CKD disease, and comorbidities. How
      to treat obesity to improve hypertension and other comorbidities in patients with
      CKD remains another important area of research.

PMID- 24076555
TI  - The buttonhole technique for fistula cannulation: pros and cons.
AB  - PURPOSE OF REVIEW: There has been increased interest in buttonhole cannulation,
      particularly in the last 5 years, because of the perceived benefit of improved
      fistula outcomes. The recent randomized trials provide for a timely review
      regarding the potential benefit and possible harms of the buttonhole technique.
      RECENT FINDINGS: The majority of observational studies report a reduction in pain
      with buttonhole; however, after reviewing the results from five randomized
      trials, buttonhole cannulation, when delivered by a nurse, does not appear to be
      less painful than rope ladder cannulation. Studies consistently report fewer
      infiltrations, reduced hematoma and a reduction of aneurysm formation with
      buttonhole. These benefits must be balanced against the increased risk of
      infection and septic complications seen with buttonhole cannulation. SUMMARY: On
      the basis of the current studies, buttonhole, when done in an in-center
      environment with many rotating staff nurses, is a complex and challenging
      technique. Buttonhole technique might be best utilized for difficult or limited
      fistula needling sites. An infection prevention education campaign along with
      regular audits regarding localized infections and bacteremias should be a
      critical part of any program which uses buttonhole cannulation. A randomized
      trial comparing buttonhole to rope ladder needling among home hemodialysis or
      self-needled patients should be the focus for future research.

PMID- 24076557
TI  - Acute kidney injury in kidney transplantation.
AB  - PURPOSE OF REVIEW: Acute kidney injury (AKI) in transplant recipients is a
      prevalent condition with a broad list of potential inciting causes. This review
      highlights recent data describing the epidemiology and long-term consequences of
      transplant AKI, novel interventions in the management of delayed graft function
      (DGF), and noninvasive diagnostic strategies. RECENT FINDINGS: The incidence and
      outcomes of nontransplant AKI are well documented, and similar data are emerging
      in the transplant setting with recent reports suggesting a high incidence rate
      and significant impact on long-term graft outcomes. DGF represents a 'pure' form
      of transplant AKI, and many interventional trials aiming to limit ischemia
      reperfusion-induced injury have recently been reported or are currently ongoing.
      The search for accurate noninvasive predictors of DGF and acute rejection is
      ongoing and recent literature describes novel plasma and urine-based biomarkers
      as well as transcriptional profiling methods with high potential for clinical
      applicability. SUMMARY: AKI in transplant recipients is a frequent occurrence
      with significant potential for poor long-term graft outcomes. Recent efforts to
      limit ischemia-reperfusion injury and diagnose transplant AKI via noninvasive
      methods may help to minimize the impact of AKI on future graft function.

PMID- 24076558
TI  - Transplanting the highly sensitized patient: trials and tribulations.
AB  - PURPOSE OF REVIEW: Humoral sensitization to antigens of the human leukocyte
      antigen and ABO systems remains one of the largest barriers to further expansion
      in renal transplantation. This barrier translates into prolonged waiting time and
      a greater likelihood of death. The number of highly sensitized patients on the
      renal transplant waiting list continues to increase. This review focuses on the
      options available to these patients and speculates on future directions for
      incompatible transplantation. RECENT FINDINGS: Desensitization protocols (to
      remove antibodies), kidney-paired donation (to circumvent antibodies) or a hybrid
      technique involving a combination of both have broadened the access to
      transplantation for patients disadvantaged by immunologic barriers. However, the
      risk of antibody-mediated rejection may be increased and warrants caution.
      Technical advances in antibody characterization using sensitive bead immunoassays
      and the C1q assay and therapeutic modalities such as complement inhibitors and
      proteasome inhibitors have been used to avoid or confront these antibody
      incompatibilities. SUMMARY: A growing body of knowledge and literature indicates
      that these diagnostic and therapeutic modalities can facilitate a safer and more
      successful treatment course for these difficult-to-treat patients. Rigorous
      investigations into newer interventions will help in broadening the options for
      these patients and also expand the living donor pool.

PMID- 24076556
TI  - New models of chronic kidney disease care including pharmacists: improving
      medication reconciliation and medication management.
AB  - PURPOSE OF REVIEW: Patients with chronic kidney disease (CKD) are complex, have
      many medication-related problems (MRPs) and high rates of medication
      nonadherence, and are less adherent to some medications than patients with higher
      levels of kidney function. Nonadherence in CKD patients increases the odds of
      uncontrolled hypertension, which can increase the risk of CKD progression. This
      review discusses reasons for gaps in medication-related care for CKD patients,
      pharmacy services to reduce these gaps and successful models that incorporate
      pharmacist care. RECENT FINDINGS: Pharmacists are currently being trained to
      deliver patient-centred care, including identification and management of MRPs and
      helping patients overcome barriers to improve medication adherence. A growing
      body of evidence indicates that pharmacist services for CKD patients, including
      medication reconciliation and medication therapy management, positively affect
      clinical and cost outcomes, including lower rates of decline in glomerular
      filtration rates, reduced mortality and fewer hospitalizations and hospital days,
      but more robust research is needed. Team-based models including pharmacists exist
      today and are being studied in a wide range of innovative care and reimbursement
      models. SUMMARY: Opportunities are growing to include pharmacists as integral
      members of CKD and dialysis healthcare teams to reduce MRPs, increase medication
      adherence and improve patient outcomes.

PMID- 24076559
TI  - Adverse effects of systemic glucose absorption with peritoneal dialysis: how good
      is the evidence?
AB  - PURPOSE OF REVIEW: Treatment of end-stage renal disease with peritoneal dialysis
      is associated with an obligatory absorption of carbohydrates with both glucose
      and icodextrin-based dialysate. In this review, we examine the evidence linking
      this obligatory absorption with adverse systemic effects. RECENT FINDINGS:
      Systemic glucose absorption is associated with worse glycemic control; this can
      be ameliorated with glucose-sparing peritoneal dialysis regimens. The studies
      examining the benefit of glucose-sparing regimens on dyslipidemia are
      inconsistent and the magnitude of benefit is potentially small. There are no
      studies demonstrating any improvement in clinically meaningful patient outcomes
      with glucose-sparing regimens. SUMMARY: Although it is conceivable that the
      obligatory carbohydrate absorption with peritoneal dialysis increases systemic
      cardiovascular risk, this premise has not been systematically or rigorously
      examined to date, there are no robust biomarkers to measure the risk,
      modification of which may favorably improve outcomes, and whether glucose-sparing
      peritoneal dialysis regimens will lower the putative risk is currently unknown.
      Hence, there is a compelling need to bridge our gap in understanding the role of
      systemic glucose absorption with peritoneal dialysis on the health of individuals
      undergoing peritoneal dialysis.

PMID- 24076560
TI  - Managing and preventing atypical hemolytic uremic syndrome recurrence after
      kidney transplantation.
AB  - PURPOSE OF REVIEW: Several genetic and acquired abnormalities leading to abnormal
      activation of the alternative pathway of complement have been identified in
      patients with atypical hemolytic uremic syndrome (aHUS). The purpose of this
      review is to shed light on how advances in the understanding of aHUS pathogenesis
      have impacted on prevention and cure of aHUS recurrence after kidney
      transplantation. RECENT FINDINGS: Studies over the past decade have shown that
      the risk of posttransplant recurrence of aHUS depends on the underlying genetic
      abnormality. The risk is high in patients with mutations in genes encoding
      circulating complement proteins and regulators, whereas patients with mutations
      in membrane cofactor protein generally show good transplant outcome. Given the
      poor outcome associated with recurrence, isolated renal transplantation had been
      contraindicated in aHUS patients. Combined kidney-liver transplantation and
      prophylactic plasma exchange have been used to prevent posttransplant
      recurrences. More recent data have provided evidence about the efficacy of the
      anti-C5 monoclonal antibody eculizumab in the prevention and treatment of
      posttransplant aHUS recurrences. SUMMARY: This review summarizes recent advances
      on preventing and managing aHUS recurrence after kidney transplantation and
      discusses the issues that still need clarification.

PMID- 24076561
TI  - Dual personality of Mad1: regulation of nuclear import by a spindle assembly
      checkpoint protein.
AB  - Nuclear transport is a dynamic process that can be modulated in response to
      changes in cellular physiology. We recently reported that the transport activity
      of yeast nuclear pore complexes (NPCs) is altered in response to kinetochore
      microtubule (KT-MT) interaction defects. Specifically, KT detachment from MTs
      activates a signaling pathway that prevents the nuclear import of cargos by the
      nuclear transport factor Kap121p. This loss of Kap121p-mediated import is thought
      to influence the nuclear environment, including the phosphorylation state of
      nuclear proteins. A key regulator of this process is the spindle assembly
      checkpoint protein Mad1p. In response to unattached KTs, Mad1p dynamically cycles
      between NPCs and KTs. This cycling appears to induce NPC molecular rearrangements
      that prevent the nuclear import of Kap121p-cargo complexes. Here, we discuss the
      underlying mechanisms and the physiological relevance of Mad1p cycling and the
      inhibition of Kap121p-mediated nuclear import, focusing on outstanding questions
      within the pathway. 

PMID- 24076562
TI  - Study on gas chromatography-mass spectrometry fingerprint of Acanthopanax
      brachypus.
AB  - As a peculiar folk medicinal plant, Acanthopanax brachypus was widely used to
      treat various diseases in China. At present, however, there is not a good quality
      standard for its quality evaluation. In this study, on the basis of the
      validation tests of precision, stability and repeatability, the chromatographic
      fingerprint of A. brachypus was established by using gas chromatography (GC)
      flame ionization detector (FID) and GC-MS techniques, as well as computer aided
      similarity evaluation system. Thirty-two different batches of samples collected
      from the different producing regions and the different parts of A. brachypus were
      studied. The results showed that the dominant constituents of all oils were
      monoterpenes and sesquiterpenes, as well as oxygenated monoterpenes and
      sesquiterpenes. The fingerprinting profiles were found to be consistent for the
      fresh stem bark acquired from various production areas, 48 common peaks were
      determined, but the relative abundance of peaks was varied. beta-Pinene,
      linalool, p-cymene, spathulenol, camphene, endo-borneol, verbenone, beta
      caryophyllene, gamma-terpinene, germacrene-D, camphor, beta-thujone and beta
      cadinene were the main constituents of the fresh stem bark oil. Except for the
      leaf, the chemical components among different medicinal parts of fresh plant were
      inconsistent with the stem bark. Besides, the varieties and relative levels of
      chemical components in the fresh stem bark were more abundant than in the dry
      counterpart. The GC-MS fingerprint can be successfully applied to distinguish the
      substitute or adulterant, and further assess the differences of A. brachypus
      grown in various areas of China. 

PMID- 24076563
TI  - Quantitative imaging of rapidly decaying evanescent fields using plasmonic near
      field scanning optical microscopy.
AB  - Non-propagating evanescent fields play an important role in the development of
      nano-photonic devices. While detecting the evanescent fields in far-field can be
      accomplished by coupling it to the propagating waves, in practice they are
      measured in the presence of unwanted propagating background components. It leads
      to a poor signal-to-noise ratio and thus to errors in quantitative analysis of
      the local evanescent fields. Here we report on a plasmonic near-field scanning
      optical microscopy (p-NSOM) technique that incorporates a nanofocusing probe for
      adiabatic focusing of propagating surface plasmon polaritons at the probe apex,
      and for enhanced coupling of evanescent waves to the far-field. In addition, a
      harmonic demodulation technique is employed to suppress the contribution of the
      background. Our experimental results show strong evidence of background free near
      field imaging using the new p-NSOM technique. Furthermore, we present
      measurements of surface plasmon cavity modes, and quantify their contributing
      sources using an analytical model. 

PMID- 24076564
TI  - Iatrogenic retained foreign body in the right atrium. Lessons to Learn.
AB  - INTRODUCTION: We report a case of a retained foreign body in the right atrium and
      the review of the literature discussing several cases where the poor attention
      and management of medical staff has led to worsening consequences to patient's
      health. PRESENTATION OF CASE: In our case the mass demonstrated on MRI scan
      turned out to be an inflammatory process and organized clotted blood built around
      a broken piece of a plastic cannula protruding out of the right atrium. This
      caused debilitating pleuritic pain to the patient on presentation. DISCUSSION:
      The cause of this iatrogenic retained piece of cannula may well be from the
      patients prior diagnostic investigations. CONCLUSION: Algorithm managed
      indications for surgical removal of such foreign bodies in symptomatic patients
      lead to better patient's outcomes and decreases the chances of infection,
      embolization, or erosions within the heart. Keeping this in view, we managed our
      patient with success.

PMID- 24076565
TI  - Invasive micropapillary carcinoma of the breast in a male patient: Report of a
      case.
AB  - INTRODUCTION: We report a rare case of invasive micropapillary carcinoma in the
      male breast. PRESENTATION OF CASE: A 63-year-old man was referred to our hospital
      for investigation of a left breast tumor, which could be palpated in the upper
      lateral quadrant of the left nipple-areola complex. The tumor invaded the areola
      skin. Ultrasonography showed a 14.8*15.0*12.4mm low echoic mass, with an
      irregular lobulated border. Core needle biopsy indicated invasive ductal
      carcinoma, but the subtype could not be accurately determined. Mastectomy with
      axillary lymph node dissection was performed. Pathological examination indicated
      invasive micropapillary carcinoma, no lymph node metastasis, and a nuclear grade
      of 2. Immunohistochemical examination showed positive staining for estrogen and
      progesterone receptors, but negative staining for HER2. The Ki67 index was 5%.
      Tamoxifen was administered, and recurrence has not been noted for 1 year.
      DISCUSSION: Women's IMPC generally shows a high HER2 positivity rate. However,
      HER2 positivity was noted in only 1 male patient with IMPC (14%) according to our
      literature review. Furthermore, in all cases of the mixed type that were
      reviewed, IMPC was associated with papillotubular carcinoma. These findings may
      be specific to IMPC in male patients. CONCLUSION: IMPC is associated with a high
      rate of lymph node metastasis or recurrence and advanced vessel invasion,
      aggressive adjuvant chemotherapy following surgical resection should be selected
      for patients with IMPC.

PMID- 24076566
TI  - Cervical leverage: A new procedure to deliver deep retrosternal goitres without
      thoracotomy.
AB  - INTRODUCTION: Although most retrosternal goitres can be removed through a
      standard collar incision, some cases require extra-cervical incisions for
      complete resection. We report a new technique to remove large retrosternal
      goitres without extra-cervical incisions. PRESENTATION OF CASE: We present two
      cases in which a US Army-Navy (Parker-Langenback) retractor was used to deliver
      large retrosternal components into the cervical incisions. DISCUSSION: This
      technique is useful in cases where the retrosternal component extends beyond the
      reach of the exploring finger and a well-developed plane can be developed between
      the gland and surrounding tissue. CONCLUSION: The cervical leverage technique
      allows removal of a large retrosternal component through a cervical incision,
      thereby avoiding the attendant morbidity of a thoracotomy or median sternotomy.
      It should not be used if there is suspected neoplastic disease, dense adherence
      to or invasion of surrounding intra-thoracic structures.

PMID- 24076567
TI  - Translational dynamics of photoexcited atoms in 4He nanodroplets: the case of
      silver.
AB  - The dynamics following the photoexcitation of Ag atoms in (4)He nanodroplets via
      the 5p (2)P1/2 <- 5s (2)S1/2 and 5p (2)P3/2 <- 5s (2)S1/2 transitions has been
      investigated in a joint experimental and theoretical effort. It has been
      experimentally found that upon excitation to the (2)P1/2 state, the Ag atoms are
      ejected with a speed distribution peaking at about 55 m s(-1). When Ag is excited
      to the (2)P3/2 state, a rich phenomenology is found. While a fraction of the
      impurities remains solvated, the impurities that are ejected from the droplets
      either as Ag or AgHe have speed distributions similar, but not identical, to
      those found for excitation to the (2)P1/2 state. The experimental findings are
      qualitatively analyzed within a three-dimensional, time-dependent density
      functional approach for the helium droplet. The dynamics of the Ag-(4)He1000
      system has been followed for several tens of picoseconds, long enough to observe
      AgHe exciplex formation and the departure of the photoexcited Ag atom from the
      helium droplet. 

PMID- 24076569
TI  - Assessing the application of advanced oxidation processes, and their combination
      with biological treatment, to effluents from pulp and paper industry.
AB  - The closure of water circuits within pulp and paper mills has resulted in a
      higher contamination load of the final mill effluent, which must consequently be
      further treated in many cases to meet the standards imposed by the legislation in
      force. Different treatment strategies based on advanced oxidation processes
      (ozonation and TiO2-photocatalysis), and their combination with biological
      treatment (MBR), are herein assessed for effluents of a recycled paper mill and a
      kraft pulp mill. Ozone treatment achieved the highest efficiency of all. The
      consumption of 2.4 g O3 L(-1) resulted in about a 60% COD reduction treating the
      effluent from the kraft pulp mill at an initial pH=7; although it only reached
      about a 35% COD removal for the effluent of the recycled paper mill. Otherwise,
      photocatalysis achieved about a 20-30% reduction of the COD for both type of
      effluents. In addition, the effluent from the recycled paper mill showed a higher
      biodegradability, so combinations of these AOPs with biological treatment were
      tested. As a result, photocatalysis did not report any significant COD reduction
      improvement whether being performed as pre- or post-treatment of the biological
      process; whereas the use of ozonation as post-biological treatment enhanced COD
      removal a further 10%, summing up a total 90% reduction of the COD for the
      combined treatment, as well as it also supposed an increase of the presence of
      volatile fatty acids, which might ultimately enable the resultant wastewater to
      be recirculated back to further biological treatment.

PMID- 24076570
TI  - Micro-structural characterization of the hydration products of bauxite
      calcination-method red mud-coal gangue based cementitious materials.
AB  - In this research, the micro-structural characterization of the hydration products
      of red mud-coal gangue based cementitious materials has been investigated through
      SEM-EDS, (27)Al MAS NMR and (29)Si MAS NMR techniques, in which the used red mud
      was derived from the bauxite calcination method. The results show that the red
      mud-coal gangue based cementitious materials mainly form fibrous C-A-S-H gel,
      needle-shaped/rod-like AFt in the early hydration period. With increasing of the
      hydration period, densification of the pastes were promoted resulting in the
      development of strength. EDS analysis shows that with the Ca/Si of red mud-coal
      gangue based cementitious materials increases, the average Ca/Si and Ca/(Si+Al)
      atomic ratio of C-A-S-H gel increases, while the average Al/Si atomic ratio of C
      A-S-H gel decreases. MAS NMR analysis reveals that Al in the hydration products
      of red mud-coal gangue based cementitious materials exists in the forms of Al(IV)
      and Al(VI), but mainly in the form of Al(VI). Increasing the Ca/Si ratio of raw
      material promotes the conversion of [AlO4] to [AlO6] and inhibits the combination
      between [AlO4] and [SiO4] to form C-A-S-H gel. Meanwhile, the polymerization
      degree of [SiO4] in the hydration products declines. 

PMID- 24076571
TI  - Photoeletrocatalytic activity of an n-ZnO/p-Cu2O/n-TNA ternary heterojunction
      electrode for tetracycline degradation.
AB  - In this study, a novel ternary heterojunction n-ZnO/p-Cu2O/n-TiO2 nanotube arrays
      (n-ZnO/p-Cu2O/n-TNA) nanophotocatalyst with a sandwich-like nanostructure was
      constructed and applied for the photoelectrocatalytic (PEC) degradation of
      typical PPCPs, tetracycline (TC). The ternary heterojunction n-ZnO/p-Cu2O/n-TNA
      was obtained by depositing Cu2O on the surface of TNA via sonoelectrochemical
      deposition (SED) and subsequently building a layer of ZnO onto the p-Cu2O/n-TNA
      surface through hydrothermal synthesis. After being deposited by the Cu2O, the
      absorption-band edge of the p-Cu2O/n-TNA was obviously red-shifted to the visible
      region (to 505 nm), and the band gap was reduced from its original 3.20 eV to
      2.46 eV. The band gap absorption edge of the ternary n-ZnO/p-Cu2O/n-TNA is
      similar to that of p-Cu2O/n-TN and extends the visible spectrum absorption to 510
      nm, corresponding to an Eg value of about 2.43 eV. Under illumination of visible
      light, the photocurrent density of the ternary heterojunction n-ZnO/p-Cu2O/n-TNA
      electrode at 0.5 V (vs. Ag/AgCl) was more than 106 times as high as that of the
      pure TNAs electrode, 3.6 times as high as that of the binary heterojunction p
      Cu2O/n-TNA electrode. The degradation of TC indicated that the ternary
      heterojunction n-ZnO/p-Cu2O/n-TNA electrode maintained a very high
      photoelectrocatalytic activity and excellent stability and reliability. Such kind
      of ternary heterojunction electrode material has a broad application prospect not
      only in pollution control but also in many other fields.

PMID- 24076568
TI  - Novel strategies targeting cancer stem cells through phytochemicals and their
      analogs.
AB  - Cancer stem cells (CSCs) are cells that exist within a tumor with a capacity of
      self-renewal and an ability to differentiate, giving rise to heterogeneous
      populations of cancer cells. These cells are increasingly being implicated in
      resistance to conventional therapeutics and have also been implicated in tumor
      recurrence. Several cellular signaling pathways including Notch, Wnt,
      phosphoinositide-3-kinase-Akt-mammalian target of rapamycin pathways, and known
      markers such as CD44, CD133, CD166, ALDH, etc. have been associated with CSCs.
      Here, we have reviewed our current understanding of self-renewal pathways and
      factors that help in the survival of CSCs with special emphasis on those that
      have been documented to be modulated by well characterized natural agents such as
      curcumin, sulforaphane, resveratrol, genistein, and epigallocatechin gallate.
      With the inclusion of a novel derivative of curcumin, CDF, we showcase how
      natural agents can be effectively modified to increase their efficacy,
      particularly against CSCs. We hope that this article will generate interest among
      researchers for further mechanistic and clinical studies exploiting the cancer
      preventive and therapeutic role of nutraceuticals by targeted elimination of
      CSCs. 

PMID- 24076573
TI  - Behaviour of fullerenes (C60) in the terrestrial environment: potential release
      from biosolids-amended soils.
AB  - Owing of their wide-range of commercial applications, fullerene (C60)
      nanoparticles, are likely to reach environments through the application of
      treated sludge (biosolids) from wastewater treatment plants to soils. We examined
      the release behaviour of C60 from contaminated biosolids added to soils with
      varying physicochemical characteristics. Incubation studies were carried out in
      the dark for up to 24 weeks, by adding biosolids spiked (1.5mg/kg) with three
      forms of C60 (suspended in water, in humic acid, and precipitated/particulate) to
      six contrasting soils. Leaching of different biosolids+soil systems showed that
      only small fractions of C60 (<5% of applied amount) were released, depending on
      incubation time and soil properties (particularly dissolved organic carbon
      content). Release of C60 from unamended soils was greater (at least twice as
      much) than from biosolids-amended soils. The form of C60 used to spike the
      biosolids had no significant effect on the release of C60 from the different
      systems. Contact time of C60 in these systems only slightly increased the
      apparent release up to 8 weeks, followed by a decrease to 24 weeks. Mass balance
      analysis at the completion of the experiment revealed that 20-60% of the initial
      C60 applied could not be accounted for in these systems; the reasons for this are
      discussed. 

PMID- 24076572
TI  - Vermiremediation: detoxification of Parthenin toxin from Parthenium weeds.
AB  - The aim of this work is the production of Parthenin toxin (sesquiterpene lactone)
      free vermicompost from Parthenium hysterophorus L. Five different concentration
      of P. hysterophorus and cow dung mixtures were vermicomposted using Eudrilus
      eugeniae. Parthenium mediated vermicompost showed an increase in plant nutrition,
      but decrease in organic carbon and phenol contents when it was compared to
      initial feed mixtures. The 30-35% of organic carbon and 32-48% of phenol contents
      were reduced during vermicomposting, which was achieved after 45 days of
      earthworm's activity. FT-IR spectra revealed the absence of Parthenin
      (sesquiterpene lactone) and phenols in vermicompost which was obtained at high
      concentration of cow dung. Earthworm's biomass gain was in low level in high
      concentration of P. hysterophorus (without cow dung). The results indicated that
      Parthenin toxin and phenols can be eradicated via vermicomposting if P.
      hysterophorus is mixed with appropriate quantity of cow dung. 

PMID- 24076574
TI  - Validation of OpenFoam for heavy gas dispersion applications.
AB  - In the present paper heavy gas dispersion calculations were performed with
      OpenFoam. For a wind tunnel test case, numerical data was validated with
      experiments. For a full scale numerical experiment, a code to code comparison was
      performed with numerical results obtained from Fluent. The validation was
      performed in a gravity driven environment (slope), where the heavy gas induced
      the turbulence. For the code to code comparison, a hypothetical heavy gas release
      into a strongly turbulent atmospheric boundary layer including terrain effects
      was selected. The investigations were performed for SF6 and CO2 as heavy gases
      applying the standard k-E turbulence model. A strong interaction of the heavy gas
      with the turbulence is present which results in a strong damping of the
      turbulence and therefore reduced heavy gas mixing. Especially this interaction,
      based on the buoyancy effects, was studied in order to ensure that the turbulence
      buoyancy coupling is the main driver for the reduced mixing and not the global
      behaviour of the turbulence modelling. For both test cases, comparisons were
      performed between OpenFoam and Fluent solutions which were mainly in good
      agreement with each other. Beside steady state solutions, the time accuracy was
      investigated. In the low turbulence environment (wind tunnel test) which for both
      codes (laminar solutions) was in good agreement, also with the experimental data.
      The turbulent solutions of OpenFoam were in much better agreement with the
      experimental results than the Fluent solutions. Within the strong turbulence
      environment, both codes showed an excellent comparability. 

PMID- 24076575
TI  - The inclusion of ADA-SCID in expanded newborn screening by tandem mass
      spectrometry.
AB  - Severe combined immunodeficiency due to adenosine-deaminase defect (ADA-SCID) is
      usually deadly in childhood because of severe recurrent infections. When clinical
      diagnosis is done, permanent damages due to infections or metabolite accumulation
      are often present. Gene therapy, bone marrow transplantation or enzyme
      replacement therapy may be effective if started early. The aim of this study was
      to set-up a robust method suitable for screening with a minimized preparation
      process and with inexpensive running costs, for diagnosing ADA-SCID by tandem
      mass spectrometry. ADA-SCID satisfies all the criteria for inclusion in a newborn
      screening program. We describe a protocol revised to incorporate adenosine and 2
      deoxyadenosine testing into an expanded newborn screening program. We assessed
      the effectiveness of this approach testing dried blood spots from 4 genetically
      confirmed early-onset and 5 delayed-onset ADA-SCID patients. Reference values
      were established on 50,000 healthy newborns (deoxyadenosine <0.09MUmol/L,
      adenosine <1.61MUmol/L). We also developed a second tier test to distinguish true
      positives from false positives and improve the positive predictive value of an
      initial abnormal result. In the first 18 months, the pilot project has identified
      a newborn with a genetically confirmed defect in adenosine deaminase (ADA) gene.
      The results show that the method having great simplicity, low cost and low
      process preparations can be fully applicable to a mass screening program. 

PMID- 24076576
TI  - Comparative tissue distribution profiles of five major bio-active components in
      normal and blood deficiency rats after oral administration of Danggui Buxue
      Decoction by UPLC-TQ/MS.
AB  - Astragali Radix (AR) and Angelicae Sinensis Radix (ASR) were frequently combined
      and used in China as herbal pair called as Danggui Buxue Decoction (DBD) for
      treatment of blood deficiency syndrome, such as women's ailments. This study is
      to investigate the tissue distribution profiles of five major bio-active
      constituents (ferulic acid, caffeic acid, calycosin-7-O-beta-glucoside, ononin
      and astragaloside IV) in DBD after oral administration of DBD in blood deficiency
      rats, and to compare the difference between normal and blood deficiency rats. The
      blood deficiency rats were induced by bleeding from orbit at the dosages of
      5.0mLkg(-1) every day, and the experimental period was 12 days. At the finally
      day of experimental period, both normal and blood deficiency rats were orally
      administrated with DBD, and then the tissues samples were collected at different
      time points. Ferulic acid, caffeic acid, calycosin-7-O-beta-glucoside, ononin and
      astragaloside IV in different tissues were detected simultaneously by UPLC-TQ/MS,
      and the histograms were drawn. The results showed that the overall trend was
      CLiver>CKidney>CHeart>CSpleen>CLung, CC-30min>CM-30min>CM-60min>CC-5min>CM
      5min>CC-60min>CM-240min>CC-240min. The contents of the detected compounds in
      liver were more than that in other tissues no matter in normal or blood
      deficiency rats. Compared to normal rats, partial contents of the compounds in
      blood deficiency rats' tissues at different time points had significant
      difference (P<0.05). This study was the first report about tissue distribution
      investigation in blood deficiency animals which is conducted by bleeding. And the
      results demonstrated that the five DBD components in normal and blood deficiency
      rats had obvious differences in some organs and time points, suggesting that the
      blood flow and perfusion rate of the organ were altered in blood deficiency
      animals. 

PMID- 24076577
TI  - Crosslinked polymer sheaths for dispersing individual single-walled carbon
      nanotubes in nonaqueous solvents.
AB  - Single-walled carbon nanotubes have been suspended individually in water by
      encasing them in a thin, uniform layer of the crosslinkable polymer poly (N
      vinylpyrrolidone-co-allylamine). When this polymer is crosslinked under dilute
      conditions, the polymer sheath, formerly stabilized by the hydrophobic effect,
      becomes stable to changes in the solvent system. 

PMID- 24076578
TI  - Immunotherapeutics for breast cancer.
AB  - PURPOSE OF REVIEW: We review recent advances leading to a new understanding of
      immunology of breast cancer with its potential clinical applications. RECENT
      FINDINGS: With the exception of antibody-based HER2 targeting, immunotherapy in
      breast cancer has largely been an unsatisfying experience. To improve the
      efficacy of breast cancer immunotherapeutics, a better understanding of the
      relation between innate and adaptive immune responses, of the immune escape
      mechanisms, the discovery of mechanisms underlying immunological tolerance, and
      the acknowledgment of the importance of both cell-mediated and humoral adaptive
      immunity for the control of tumor growth are needed. SUMMARY: Cancer takes
      advantage of the ability to hide from the immune system by exploiting a series of
      immune escape mechanisms. Among these mechanisms are the hijackings of immune
      cell-intrinsic checkpoints that are induced on T-cell activation. Blockade of
      these checkpoints - cytotoxic T-lymphocyte-associated antigen 4 or the programmed
      death 1 receptor - recently provided the first evidence of activity of an immune
      modulation approach in the treatment of solid tumors. The future frontier in the
      immunotherapeutics of breast cancer requires identification of predictive
      factors. The immune system remembers what it targets, so once the system is
      correctly activated, it may mediate a long-lasting tumor response.

PMID- 24076579
TI  - Management of relapsed acute lymphoblastic leukemia in childhood with
      conventional and innovative approaches.
AB  - PURPOSE OF REVIEW: To review and summarize the available evidence on factors
      predicting prognosis of children with relapsed acute lymphoblastic leukemia (ALL)
      and on the currently used treatment strategies, as well as on the most promising
      and innovative molecular or cellular therapies. RECENT FINDINGS: Relapse still
      represents the most common cause of treatment failure, occurring in approximately
      15-20% of childhood ALL. Risk-oriented standard salvage regimens are mostly based
      on combinations of the same agents incorporated in frontline therapies.
      Allogeneic hematopoietic stem cell transplantation (HSCT) is largely employed as
      postremission therapy, being superior to chemotherapy in high-risk patients. With
      conventional therapies including HSCT, 40-50% of children with relapsed ALL can
      be rescued. Thus, innovative approaches are needed to further improve the outcome
      of patients, especially when carrying poor prognostic factors. The last decade
      has witnessed the development of novel agents, including nucleoside analogues,
      anti-CD22 monoclonal antibodies and bi-specific, anti-CD3/CD19 antibodies,
      together with new formulations of existing chemotherapeutic agents and targeted
      molecules, such as tyrosine kinase inhibitors and FLT3 inhibitors. SUMMARY: A
      significant proportion of children with relapsed ALL are salvaged by risk
      oriented therapies. Novel agents should be integrated into combination regimens
      with the aim of further improving outcome of patients.

PMID- 24076580
TI  - Recent advances in the management of mantle cell lymphoma.
AB  - PURPOSE OF REVIEW: This review will discuss the most recent literature regarding
      frontline therapy, treatment of patients not eligible for intensive chemotherapy,
      and novel agents for relapsed/refractory patients with mantle cell lymphoma
      (MCL). RECENT FINDINGS: Longer follow-up of previously studied intensive regimens
      still demonstrates encouraging results, but late relapses are still evident.
      Consolidation and maintenance strategies continue to be attractive options to be
      explored in this disease that is characterized by frequent relapses and short
      remissions. The combination of bendamustine-rituximab was demonstrated to be
      noninferior and less toxic to R-CHOP and should be considered the new standard of
      care for elderly patients. Multiple novel agents directed towards different
      molecular targets like BTK, mTOR, PI3K, HDAC, and BCL-2, involved in the
      pathogenesis of MCL have shown promising results. SUMMARY: Management of MCL
      still represents a challenge due to heterogeneity of the disease. As we approach
      the molecular era of oncology, future strategies should focus on combination of
      newer agents with known effective regimens to improve outcome.

PMID- 24076581
TI  - Medulloblastoma molecular dissection: the way toward targeted therapy.
AB  - PURPOSE OF REVIEW: The advent of integrated genomics revealed profound insights
      into medulloblastoma pathogenesis. However, these biological findings have yet to
      be translated into the clinic, as current treatment comprises surgical resection,
      conventional irradiation, and chemotherapy resulting in significant long-term
      sequelae. We sought to highlight the potential areas for targeted therapy based
      on our new understanding of the subgroup-specific tumor biology. RECENT FINDINGS:
      Recently, four distinct molecular subgroups of medulloblastoma have been
      identified [WNT (wingless), SHH (sonic hedgehog), Group 3, and Group 4].
      Profiling of these subgroups revealed distinct genomic events, several of which
      represent actionable targets for therapy. Specifically, stratification of
      patients into their respective subgroups has profound prognostic impact, wherein
      therapy can be de-escalated in patients with favorable prognosis, and intensified
      therapy or novel agents can be considered in patients with poor prognosis. Novel
      subgroup-specific therapies are being explored in clinical trials, particularly
      for the SHH subgroup. Epigenetic modifiers are also recurrently affected in
      medulloblastoma suggesting that epigenetic therapy can be considered in a subset
      of patients. SUMMARY: The identification of subgroup-specific, actionable
      therapeutic targets has the potential to revolutionize therapy for
      medulloblastoma patients, and result in significantly improved quality of life in
      survivors and improved overall survival.

PMID- 24076582
TI  - Biology and management of therapy-related acute promyelocytic leukemia.
AB  - PURPOSE OF REVIEW: Therapy-related acute promyelocytic leukemia (t-APL) has been
      increasingly reported after exposure to cytotoxic and/or immunosuppressive agents
      given for prior malignancies or autoimmune diseases. t-APL represents both a
      model for better understanding human leukemogenesis and an interesting
      therapeutic subset which requires specific adaptations for optimal management.
      RECENT FINDINGS: We discuss here potential risk factors for t-APL development and
      the main biologic and clinical characteristics of t-APL as compared to de-novo
      APL.In addition, we review therapeutic results obtained in patients with t-APL
      receiving conventional retinoic acid and chemotherapy and discuss new treatment
      opportunities with minimal or no exposure to conventional cytotoxic agents.
      SUMMARY: Genomic studies in patients at risk of t-APL are relevant to better
      adapt treatment for the primary disease and to implement monitoring during follow
      up and early diagnosis of t-APL. Improved molecular characterization of t-APL may
      include next generation sequencing approaches to better identify distinguishing
      features as compared to de-novo APL. Early diagnosis of t-APL through careful
      monitoring of patients at higher risk, coupled to incorporation in the
      therapeutic armamentarium of novel effective agents such as arsenic trioxide
      could result in improved clinical outcome for these patients.

PMID- 24076583
TI  - Predictive biomarkers in adult gliomas: the present and the future.
AB  - PURPOSE OF REVIEW: This review summarizes recent studies on the predictive value
      of molecular markers in adult gliomas, including 1p/19q codeletion, MGMT
      methylation, IDH mutation and markers identified using omics and next-generation
      sequencing studies. RECENT FINDINGS: The long-term results of the Radiation
      Therapy Oncology Group and European Organization for Research and Treatment of
      Cancer trials in anaplastic oligodendroglial glioma have shown that the 1p/19q
      codeletion predicts an overall survival benefit from early PCV (procarbazine CCNU
      vincristine) chemotherapy. This benefit can also be predicted using gene
      expression-based molecular subtypes of gliomas while the predictive value of the
      IDH mutation in this context requires further study. In elderly patients with
      glioblastoma, the analysis of MGMT methylation status in two phase III trials
      suggests that this alteration may guide treatment decisions; however, this
      finding still needs confirmation in prospective studies. Omics and next
      generation sequencing studies have identified additional potential predictive
      markers. In particular, IDH mutations, BRAF V600E mutations and FGFR gene fusions
      might predict efficacy of therapies targeted against these alterations. SUMMARY:
      Currently, the 1p/19q codeletion is the only well established predictive marker
      with clinical utility. However, it is likely that other molecular markers such as
      MGMT methylation, IDH mutation and those identified using omics and next
      generation sequencing studies will further guide treatment decisions in adult
      gliomas.

PMID- 24076585
TI  - Sparse Methods for Biomedical Data.
AB  - Following recent technological revolutions, the investigation of massive
      biomedical data with growing scale, diversity, and complexity has taken a center
      stage in modern data analysis. Although complex, the underlying representations
      of many biomedical data are often sparse. For example, for a certain disease such
      as leukemia, even though humans have tens of thousands of genes, only a few genes
      are relevant to the disease; a gene network is sparse since a regulatory pathway
      involves only a small number of genes; many biomedical signals are sparse or
      compressible in the sense that they have concise representations when expressed
      in a proper basis. Therefore, finding sparse representations is fundamentally
      important for scientific discovery. Sparse methods based on the [Formula: see
      text] norm have attracted a great amount of research efforts in the past decade
      due to its sparsity-inducing property, convenient convexity, and strong
      theoretical guarantees. They have achieved great success in various applications
      such as biomarker selection, biological network construction, and magnetic
      resonance imaging. In this paper, we review state-of-the-art sparse methods and
      their applications to biomedical data.

PMID- 24076584
TI  - Current status of interleukin-10 and regulatory T-cells in cancer.
AB  - PURPOSE OF REVIEW: Tumor growth elicits antigen-specific cytotoxic as well as
      immune suppressive responses. Interleukin-10 (IL-10) is a key immune-suppressive
      cytokine produced by regulatory T-cells and by helper T-cells. Here, we review
      pleiotropic functions of IL-10 that impact the immune pathology of cancer. RECENT
      FINDINGS: The role of IL-10 in cancer has become less certain with the knowledge
      of its immune stimulatory functions. IL-10 is needed for T-helper cell functions,
      T-cell immune surveillance, and suppression of cancer-associated inflammation. By
      promoting tumor-specific immune surveillance and hindering pathogenic
      inflammation, IL-10 is emerging as a key cytokine in the battle of the host
      against cancer. SUMMARY: IL-10 functions at the cross-roads of immune stimulation
      and immune suppression in cancer. Immunological mechanisms of action of IL-10 can
      be ultimately exploited to develop novel and effective cancer therapies.

PMID- 24076586
TI  - The role, mechanism and potentially therapeutic application of microRNA-29 family
      in acute myeloid leukemia.
AB  - Abnormal proliferation, apoptosis repression and differentiation blockage of
      hematopoietic stem/progenitor cells have been characterized to be the main
      reasons leading to acute myeloid leukemia (AML). Previous studies showed that miR
      29a and miR-29b could function as tumor suppressors in leukemogenesis. However, a
      comprehensive investigation of the function and mechanism of miR-29 family in AML
      development and their potentiality in AML therapy still need to be elucidated.
      Herein, we reported that the family members, miR-29a, -29b and -29c, were
      commonly downregulated in peripheral blood mononuclear cells and bone marrow (BM)
      CD34+ cells derived from AML patients as compared with the healthy donors.
      Overexpression of each miR-29 member in THP1 and NB4 cells markedly inhibited
      cell proliferation and promoted cell apoptosis. AKT2 and CCND2 mRNAs were
      demonstrated to be targets of the miR-29 members, and the role of miR-29 family
      was attributed to the decrease of Akt2 and CCND2, two key signaling molecules.
      Significantly increased Akt2, CCND2 and c-Myc levels in the AML cases were
      detected, which were correlated with the decreased miR-29 expression in AML
      blasts. Furthermore, a feed-back loop comprising of c-Myc, miR-29 family and Akt2
      were found in myeloid leukemogenesis. Reintroduction of each miR-29 member
      partially corrected abnormal cell proliferation and apoptosis repression and
      myeloid differentiation arrest in AML BM blasts. An intravenous injection of miR
      29a, -29b and -29c in the AML model mice relieved leukemic symptoms
      significantly. Taken together, our finding revealed a pivotal role of miR-29
      family in AML development and rescue of miR-29 family expression in AML patients
      could provide a new therapeutic strategy. 

PMID- 24076587
TI  - Mapping the p53 transcriptome universe using p53 natural polymorphs.
AB  - The tumor suppressor p53 has defined roles in varied cellular processes including
      apoptosis and DNA repair. While conventional genomic approaches have suggested a
      large number of p53 targets, there is a need for a systematic approach to
      validate these putative genes. We developed a method to identify and validate
      p53's transcriptional behavior by utilizing 16 non-synonymous p53 single
      nucleotide polymorphism (SNP) variants. Five SNPs located within the DNA-binding
      domain of p53 were found to be functionally null, whereas the other 11 SNPs were
      p53WT-like in behavior. By integrating p53 ChIP-seq analysis with transcriptome
      data from the p53 SNP variants, 592 genes were identified as novel p53 targets.
      Many of these genes mapped to previously less well-characterized aspects of p53
      function, such as cell signalling, metabolism, central nervous system, and immune
      system. These data provide pivotal insights into the involvement of p53 in
      diverse pathways of normal physiological processes and open new avenues for
      investigation of p53 function. 

PMID- 24076589
TI  - Enzalutamide: The emperor of all anti-androgens.

PMID- 24076588
TI  - A novel subset of helper T cells promotes immune responses by secreting GM-CSF.
AB  - Helper T cells are crucial for maintaining proper immune responses. Yet, they
      have an undefined relationship with one of the most potent immune stimulatory
      cytokines, granulocyte macrophage-colony-stimulating factor (GM-CSF). By
      depleting major cytokines during the differentiation of CD4(+) T cells in vitro,
      we derived cells that were found to produce large amounts of GM-CSF, but little
      of the cytokines produced by other helper T subsets. By their secretion of GM
      CSF, this novel subset of helper T cells (which we have termed ThGM cells)
      promoted the production of cytokines by other T-cell subtypes, including type 1
      helper T cell (Th1), type 2 helper T cell (Th2), type 1 cytotoxic T cell (Tc1),
      type 2 cytotoxic T cell (Tc2), and naive T cells, as evidenced by the fact that
      antibody neutralization of GM-CSF abolished this effect. ThGM cells were found to
      be highly prone to activation-induced cell death (AICD). Inhibitors of TRAIL or
      granzymes could not block AICD in ThGM cells, whereas inhibition of FasL/Fas
      interaction partially rescued ThGM cells from AICD. Thus, ThGM cells are a novel
      subpopulation of T helper cells that produce abundant GM-CSF, exhibit exquisite
      susceptibility to apoptosis, and therefore play a pivotal role in the regulation
      of the early stages of immune responses. 

PMID- 24076590
TI  - Construction and expression of hepatitis B surface antigen escape variants within
      the "a" determinant by site directed mutagenesis.
AB  - BACKGROUND: The antibody response to hepatitis B surface antigen (HBsAg) controls
      hepatitis B virus infection. The "a" determinant of HBsAg is the most important
      target for protective antibody response, diagnosis and immunoprophylaxis.
      Mutations in this area may induce immune escape mutants and affect the
      performance of HBsAg assays. OBJECTIVES: To construct clinically relevant
      recombinant mutant forms of HBsAg and assessment of their reactivity with anti
      HBs monoclonal antibodies (MAbs). METHODS: Wild type (wt) and mutant (mt) HBsAg
      genes were constructed by site directed mutagenesis and SEOing PCR. The amplified
      genes were inserted into pCMV6-neo plasmid and transfected in CHO cell line. The
      expression of wt- and mtHBsAg was assessed by commercial ELISA assays and stable
      cells were established and cloned by limiting dilution. The recombinant mutants
      were further characterized using a panel of anti-HBs monoclonal antibodies (MAbs)
      and the pattern of their reactivity was assessed by ELISA. RESULTS: Ten HBsAg
      mutants having single mutation within the "a" determinant including P120E, T123N,
      Q129H, M133L, K141E, P142S, D144A, G145R, N146S and C147S together with a wt form
      were successfully constructed and expressed in CHO cells. Reactivity of anti-HBs
      MAbs with mtHBsAgs displayed different patterns. The effect of mutations on
      antibody binding differed depending on the amino acid involved and its location
      within the ''a'' determinant. Mutation at amino acids 123 and 145 resulted in
      either complete loss or significant reduction of binding to all anti-HBs MAbs.
      CONCLUSION: Our panel of mtHBsAgs is a valuable tool for assessment of the
      antibody response to HBV escape mutants and may have substantial implications in
      HBV immunological diagnostics.

PMID- 24076591
TI  - Arteether exerts antitumor activity and reduces CD4+CD25+FOXP3+ T-reg cells in
      vivo.
AB  - BACKGROUND: Chemo-immunotherapy is one of the new achievements for treatment of
      cancer, by which the success of anti-cancer therapy can be increased. In vitro
      studies have been shown that Arteether (ARE) induces apoptosis in tumor cells,
      but not in normal cells. OBJECTIVE: To investigate the cytotoxic and
      immunomodulatory properties of Arteether in-vivo and in-vitro. METHODS: In this
      study, we used MTT assay for evaluation of cytotoxicity of Arteether on tumor
      cell line and Peripheral Blood Mononuclear Cells (PBMCs) from healthy
      individuals. Balb/c mice were subcutaneously transplanted with tumor tissue taken
      from Spontaneous Mouse Mammary Tumor (SMMT) bearing female mice. Arteether was
      administered to breast tumor-bearing Balb/c mice at a dose of 6mg/kg/day
      intraperitoneally. Tumor sizes, lymphocyte proliferation, cytokines production,
      and the percentage of splenic T-reg cells were measured. RESULTS: We observed
      that ARE could reduce the cell growth of 4T1 cell line in a dose-dependent manner
      but it had no cytotoxic effect on the growth of peripheral blood lymphocytes. ARE
      administered intraperitoneally to tumor-bearing Balb/c mice could reduce the
      tumor growth rate and splenic T-reg cells. No difference in the IFN-gamma, IL-10
      and IL-4 production was observed between tumor antigen-stimulated splenocytes of
      mice treated with ARE and control mice. CONCLUSION: These results underscore
      antitumor properties of Arteether that may aid in development of more effective
      antitumor agents.

PMID- 24076592
TI  - KIR gene content does not contribute to susceptibility to Graves' disease.
AB  - BACKGROUND: Killer cell immunoglobulin-like receptors (KIR) are expressed on NK
      cells and a subset of T cells. The variable KIR receptors along with their
      ligands, HLA class I, influence risk for autoimmune and malignant diseases.
      OBJECTIVE: To investigate the KIR gene profiles in relation to susceptibility to
      Graves' disease in patients with ophthalmopathy. METHODS: KIR genes profiles were
      analyzed in 90 patients presenting Graves' disease with ophthalmopathy
      representing upper eyelid retraction, swelling, redness, conjunctivitis, and
      bulging eyes and were compared with the KIR gene profiles of 112 healthy
      controls. The presence and absence of 11 variable KIR genes were characterized
      using a gene-specific PCR typing system. RESULTS: There was no significant
      difference in the distribution of KIR gene profiles between patients and
      controls. CONCLUSION: Our data show that none of the KIR genotypes contribute in
      susceptibility to Graves' disease; although the role of HLA ligand remains to be
      characterized.

PMID- 24076593
TI  - Interleukin-8 but not interleukin-6 variant may affect susceptibility to
      brucellosis.
AB  - BACKGROUND: Increased levels of interleukin-8 (IL-8) and interleukin-6 (IL-6) in
      acute human brucellosis have been reported. Previous studies have shown that the
      production and level of IL-6 and IL-8 cytokines are associated with the
      polymorphism of the encoding genes. OBJECTIVE: To investigate the probable
      association between IL-6 (-174 C/G) and IL-8 (-251 A/T) gene polymorphisms and
      susceptibility/resistance to brucellosis. METHODS: The patient group included 196
      patients suffering from Brucella infection and the control group consisted of 82
      healthy animal husbandmen from the same geographical area. IL-8 (-251 A/C) and IL
      6 (-174 C/G) gene polymorphisms were analyzed by PCR-RFLP and Allele Specific PCR
      (AS-PCR) respectively. RESULTS: The frequency of -251 IL-8 AA genotype was
      significantly lower in the controls compared with that of the patients
      (p=0.0051), while the frequencies of other genotypes (AT and TT) and alleles (A
      and T) were not significantly different among the participants. No association
      was found between IL-6 (-174 C/G) polymorphism and brucellosis. CONCLUSION: This
      study indicates that the IL-8 -251 AA genotype may be considered as a genetic
      susceptibility factor for brucellosis.

PMID- 24076594
TI  - Serum IL-18 and hsCRP correlate with insulin resistance without effect of
      calcitriol treatment on type 2 diabetes.
AB  - BACKGROUND: Chronic low-grade systemic inflammation presented in Type 2 diabetes
      mellitus plays a major role in disease progression as well as development of
      micro- and macro-vascular complications of diabetes. Therefore, reducing
      inflammation can be beneficial in prevention of diabetes complications.
      OBJECTIVES: To investigate the association between insulin resistance and
      inflammatory markers, and assessing the effects of oral Calcitriol on
      inflammatory cytokines in type 2 diabetic patients. METHODS: In this double-blind
      randomized placebo-controlled trial, 70 participants with type-2 diabetes were
      randomly divided to two groups. One group received two capsules of Calcitriol
      (0.25 MUg 1,25-dihydroxy cholecalciferol per each capsule) per day. The second
      group received placebo tablets. At the beginning of the study, we assessed
      insulin resistance and its relation to inflammatory profile. Serum high sensitive
      C-reactive protein (hs CRP), interleukin-6 and interleukin-18 were also measured
      at the beginning and the end of the 12-week supplementation trial. RESULTS: Mean
      calcium, phosphorus and vitamin D concentrations in the study participants were
      8.98 +/- 0.79 mg/dL, 3.86 +/- 0.50 mg/dL and 40.91 +/- 30.9 ng/mL, respectively.
      IL-18 and hsCRP had significant positive associations with insulin resistance
      markers and negative associations with insulin sensitivity markers. At the end of
      the 12-week supplementation trial, no significant difference was seen in serum
      levels of hsCRP, IL-6 and IL-18 between the two groups, while these values were
      adjusted for baseline values. CONCLUSION: Inflammation was associated with
      insulin resistance in diabetic patients. No anti-inflammatory effect of
      Calcitriol in terms of decreasing hsCRP, IL-6 and IL-18 detected.

PMID- 24076595
TI  - Interleukin-17 gene expression and serum levels in children with severe asthma.
AB  - BACKGROUND: IL-17 is a major cytokine player in T cell mediated leukocyte
      associated inflammation. IL-17 is also recognized to participate in the
      pathophysiology of asthma. OBJECTIVE: To determine the role of IL-17 in
      predicting severe asthma. METHODS: We obtained serum samples from asthmatic
      children under the age of 5-year in three different groups of mild (n=33),
      moderate (n=28) and severe (n=32) persistent asthma. IL-17 serum concentrations
      and mRNA expression were determined by ELISA and real time PCR assays,
      respectively. RESULTS: Serum IL-17 concentrations were significantly higher in
      patients with severe asthma than the other two groups of children with mild and
      moderate disease (p=0.00). Mean serum IL-17 values were 142.04 pg/ml in mild
      group, 180.4 pg/ml in moderate group and 251.25 pg/ml in severe group. IL-17 mRNA
      levels were also significantly elevated in severe asthmatic patients compared to
      mild and moderate asthmatic children (p=0.00). CONCLUSION: Our data reveal an
      increase in the serum IL-17 concentration and IL-17 mRNA expression in children
      with severe asthma compared to those with mild and moderate forms of the disease.

PMID- 24076596
TI  - A peculiar case of splenic marginal zone lymphoma and review of literature.

PMID- 24076597
TI  - Does nitric oxide generated by dendritic cells contribute to the low incidence of
      GVHD after cord blood transplantation?

PMID- 24076598
TI  - Controlling cellular uptake of nanoparticles with pH-sensitive polymers.
AB  - The major challenge in cancer therapy is to efficiently translocate drug
      molecules into cancer tumors without doing any damage to healthy tissues. Since
      there exist pH gradients between tumor and normal tissues, pH-sensitive materials
      may have great potential to overcome such challenge. Here, we report one new type
      of pH-responsive drug delivery system where pH-sensitive polymers are introduced
      to control the cellular uptake of nanoparticles under different pH environments
      through dissipative particle dynamics simulations. Interestingly, the behavior of
      cellular uptake of nanoparticles here exhibits "smart" pH-responsive properties:
      for lower and higher pH, the nanoparticles can be taken up by cell membranes,
      while for pH in middle range, the endocytosis is blocked. Further, it is found
      that receptor-ligand interactions as well as surface charge property of
      nanoparticles and membranes can also have important impacts on the endocytosis.
      The present study may give some significant insights into future stimulus
      responsive medical materials design. 

PMID- 24076599
TI  - Comparative analysis of empiric antimicrobial treatments for skin and soft tissue
      infections in newly hospitalized patients.
AB  - PURPOSE: Intravenous vancomycin is the standard empiric treatment for complicated
      skin and soft tissue infections (SSTIs) due to its coverage against methicillin
      resistant Staphylococcus aureus (MRSA). The objective of this study was to
      compare the hospital length of stay (LOS) between vancomycin-treated patients and
      patients receiving newer anti-MRSA agents. The study also aimed to identify
      factors associated with therapy change in patients receiving vancomycin on
      admission. METHODS: Electronic medical records were used to conduct this
      retrospective cohort study. The LOS was compared among 5 groups of adult patients
      with admission diagnoses for SSTI who were initiated on linezolid, daptomycin,
      ceftaroline, tigecycline, or vancomycin. Survival analysis was used to identify
      factors associated with therapy change from vancomycin to another study
      medication. RESULTS: Vancomycin was prescribed in 1046 (92%) admissions. Although
      none of the between-group differences in LOS reached statistical significance,
      there was a trend toward shorter LOS in vancomycin-treated patients compared to
      linezolid-treated patients (P = .059). Coagulopathy was independently associated
      with increased likelihood of therapy change from vancomycin (hazard ratio = 4.71;
      P <.001). CONCLUSIONS: In the treatment of SSTI, newer agents result in LOS
      comparable to vancomycin. In patients initiated on vancomycin, therapy change was
      associated with longer LOS. Coagulopathy was independently associated with
      increased probability of therapy change.

PMID- 24076600
TI  - BMP signaling controls muscle mass.
AB  - Cell size is determined by the balance between protein synthesis and degradation.
      This equilibrium is affected by hormones, nutrients, energy levels, mechanical
      stress and cytokines. Mutations that inactivate myostatin lead to excessive
      muscle growth in animals and humans, but the signals and pathways responsible for
      this hypertrophy remain largely unknown. Here we show that bone morphogenetic
      protein (BMP) signaling, acting through Smad1, Smad5 and Smad8 (Smad1/5/8), is
      the fundamental hypertrophic signal in mice. Inhibition of BMP signaling causes
      muscle atrophy, abolishes the hypertrophic phenotype of myostatin-deficient mice
      and strongly exacerbates the effects of denervation and fasting. BMP-Smad1/5/8
      signaling negatively regulates a gene (Fbxo30) that encodes a ubiquitin ligase
      required for muscle loss, which we named muscle ubiquitin ligase of the SCF
      complex in atrophy-1 (MUSA1). Collectively, these data identify a critical role
      for the BMP pathway in adult muscle maintenance, growth and atrophy.

PMID- 24076601
TI  - The long noncoding RNA SChLAP1 promotes aggressive prostate cancer and
      antagonizes the SWI/SNF complex.
AB  - Prostate cancers remain indolent in the majority of individuals but behave
      aggressively in a minority. The molecular basis for this clinical heterogeneity
      remains incompletely understood. Here we characterize a long noncoding RNA termed
      SChLAP1 (second chromosome locus associated with prostate-1; also called
      LINC00913) that is overexpressed in a subset of prostate cancers. SChLAP1 levels
      independently predict poor outcomes, including metastasis and prostate cancer
      specific mortality. In vitro and in vivo gain-of-function and loss-of-function
      experiments indicate that SChLAP1 is critical for cancer cell invasiveness and
      metastasis. Mechanistically, SChLAP1 antagonizes the genome-wide localization and
      regulatory functions of the SWI/SNF chromatin-modifying complex. These results
      suggest that SChLAP1 contributes to the development of lethal cancer at least in
      part by antagonizing the tumor-suppressive functions of the SWI/SNF complex.

PMID- 24076603
TI  - Truncating mutations of MAGEL2 cause Prader-Willi phenotypes and autism.
AB  - Prader-Willi syndrome (PWS) is caused by the absence of paternally expressed,
      maternally silenced genes at 15q11-q13. We report four individuals with
      truncating mutations on the paternal allele of MAGEL2, a gene within the PWS
      domain. The first subject was ascertained by whole-genome sequencing analysis for
      PWS features. Three additional subjects were identified by reviewing the results
      of exome sequencing of 1,248 cases in a clinical laboratory. All four subjects
      had autism spectrum disorder (ASD), intellectual disability and a varying degree
      of clinical and behavioral features of PWS. These findings suggest that MAGEL2 is
      a new gene causing complex ASD and that MAGEL2 loss of function can contribute to
      several aspects of the PWS phenotype.

PMID- 24076604
TI  - Global chromatin profiling reveals NSD2 mutations in pediatric acute
      lymphoblastic leukemia.
AB  - Epigenetic dysregulation is an emerging hallmark of cancers. We developed a high
      information-content mass spectrometry approach to profile global histone
      modifications in human cancers. When applied to 115 lines from the Cancer Cell
      Line Encyclopedia, this approach identified distinct molecular chromatin
      signatures. One signature was characterized by increased histone 3 lysine 36
      (H3K36) dimethylation, exhibited by several lines harboring translocations in
      NSD2, which encodes a methyltransferase. A previously unknown NSD2 p.Glu1099Lys
      (p.E1099K) variant was identified in nontranslocated acute lymphoblastic leukemia
      (ALL) cell lines sharing this signature. Ectopic expression of the variant
      induced a chromatin signature characteristic of NSD2 hyperactivation and promoted
      transformation. NSD2 knockdown selectively inhibited the proliferation of NSD2
      mutant lines and impaired the in vivo growth of an NSD2-mutant ALL xenograft.
      Sequencing analysis of >1,000 pediatric cancer genomes identified the NSD2
      p.E1099K alteration in 14% of t(12;21) ETV6-RUNX1-containing ALLs. These findings
      identify NSD2 as a potential therapeutic target for pediatric ALL and provide a
      general framework for the functional annotation of cancer epigenomes.

PMID- 24076602
TI  - Analysis of immune-related loci identifies 48 new susceptibility variants for
      multiple sclerosis.
AB  - Using the ImmunoChip custom genotyping array, we analyzed 14,498 subjects with
      multiple sclerosis and 24,091 healthy controls for 161,311 autosomal variants and
      identified 135 potentially associated regions (P < 1.0 * 10(-4)). In a
      replication phase, we combined these data with previous genome-wide association
      study (GWAS) data from an independent 14,802 subjects with multiple sclerosis and
      26,703 healthy controls. In these 80,094 individuals of European ancestry, we
      identified 48 new susceptibility variants (P < 5.0 * 10(-8)), 3 of which we found
      after conditioning on previously identified variants. Thus, there are now 110
      established multiple sclerosis risk variants at 103 discrete loci outside of the
      major histocompatibility complex. With high-resolution Bayesian fine mapping, we
      identified five regions where one variant accounted for more than 50% of the
      posterior probability of association. This study enhances the catalog of multiple
      sclerosis risk variants and illustrates the value of fine mapping in the
      resolution of GWAS signals.

PMID- 24076606
TI  - Prognostic value of shock index in children with septic shock.
AB  - OBJECTIVES: Septic shock is frequent in children and is associated with high
      mortality and morbidity rates. Early recognition of severe sepsis improve
      outcome. Shock index (SI), ratio of heart rate (HR) and systolic blood pressure
      (SBP), may be a good noninvasive measure of hemodynamic instability that has been
      poorly studied in children. The aim of the study was to explore the usefulness of
      SI as an early index of prognosis for septic shock in children. METHODS: The
      study was retrospective and performed in 1 pediatric intensive care unit at a
      university hospital. The following specific data were collected at 0, 1, 2, 4,
      and 6 hours after admission: HR and SBP for SI calculation and lactate
      concentration. Patients were divided into 2 groups according to their outcome
      (death/survival). RESULTS: A total of 146 children admitted with septic shock
      between January 2000 and April 2010 were included. Shock index was significantly
      different between survivors and nonsurvivors at 0, 4, and 6 hours after admission
      (P = 0.02, P = 0.03, and P = 0.008, respectively). Age-adjusted SIs were
      different between survivors and nonsurvivors at 0 and 6 hours, with a relative
      risk of death at these time points of 1.85 (1.04-3.26) (P = 0.03) and 2.17 (1.18
      3.96) (P = 0.01), respectively. Moreover, an abnormal SI both at admission and at
      6 hours was predictive of death with relative risk of 1.36 (1.05-1.76).
      CONCLUSIONS: In our population of children with septic shock, SI was a clinically
      relevant and easily calculated predictor of mortality. It could be a better
      measure of hemodynamic status than HR and SBP alone, allowing for the early
      recognition of severe sepsis.

PMID- 24076605
TI  - Population-based biomonitoring of exposure to organophosphate and pyrethroid
      pesticides in New York City.
AB  - BACKGROUND: Organophosphates and pyrethroids are the most common classes of
      insecticides used in the United States. Widespread use of these compounds to
      control building infestations in New York City (NYC) may have caused higher
      exposure than in less-urban settings. OBJECTIVES: The objectives of our study
      were to estimate pesticide exposure reference values for NYC and identify
      demographic and behavioral characteristics that predict exposures. METHODS: The
      NYC Health and Nutrition Examination Survey was a population-based, cross
      sectional study conducted in 2004 among adults >= 20 years of age. It measured
      urinary concentrations of organophosphate metabolites [dimethylphosphate (DMP),
      dimethylthiophosphate (DMTP), dimethyldithiophosphate, diethylphosphate,
      diethylthiophosphate, and diethyldithiophosphate] in 883 participants, and
      pyrethroid metabolites [3-phenoxybenzoic acid (3-PBA), trans-3-(2,2
      dichlorovinyl)-2,2-dimethylcyclopropane-1-carboxylic acid (trans-DCCA), 4-fluoro
      3-phenoxybenzoic acid, and cis-3-(2,2-dibromovinyl)-2,2-dimethylcyclopropane-1
      carboxylic acid] in 1,452 participants. We used multivariable linear regression
      to estimate least-squares geometric mean total dialkylphospate (SigmaDAP) and 3
      PBA concentrations across categories of predictors. RESULTS: The dimethyl
      organophosphate metabolites had the highest 95th percentile concentrations (87.4
      MUg/L and 74.7 MUg/L for DMP and DMTP, respectively). The highest 95th
      percentiles among pyrethroid metabolites were measured for 3-PBA and trans-DCCA
      (5.23 MUg/L and 5.94 MUg/L, respectively). Concentrations of SigmaDAP increased
      with increasing age, non-Hispanic white or black compared with Hispanic
      race/ethnicity, professional pesticide use, and increasing frequency of fruit
      consumption; they decreased with non-green vegetable consumption. Absolute
      differences in geometric mean urinary 3-PBA concentrations across categories of
      predictors were too small to be meaningful. CONCLUSION: Estimates of exposure to
      pyrethroids and dimethyl organophosphates were higher in NYC than in the United
      States overall, underscoring the importance of considering pest and pesticide
      burdens in cities when formulating pesticide use regulations.

PMID- 24076607
TI  - Evaluation of a novel pediatric appendicitis pathway using high- and low-risk
      scoring systems.
AB  - OBJECTIVES: This study aimed to determine the test characteristics of a pathway
      for pediatric appendicitis and its effects on emergency department (ED) length of
      stay, imaging, and admissions. METHODS: Children age 3 to 18 years with suspicion
      for appendicitis at 1 tertiary care ED were prospectively enrolled, using
      validated low- and high-risk scoring systems incorporating history, physical
      examination, and white blood cell count. Low-risk patients were discharged or
      observed in the ED. High-risk patients were admitted. Those meeting neither low
      risk nor high-risk criteria were evaluated by surgery, with imaging at their
      discretion. Chart review or telephone follow-up was conducted 2 weeks after the
      visit. A retrospective study before and after was also performed. Charts of a
      random sample of patients evaluated for appendicitis in the 8 months before and
      after the pathway implementation were reviewed. RESULTS: Appendicitis was
      diagnosed in 65 of 178 patients. Of those with appendicitis, 63 were not low-risk
      (sensitivity, 96.9%; specificity, 40.7%). The high-risk criteria had a
      sensitivity of 75.3% and specificity of 75.2%. We reviewed 292 visits before and
      290 after the pathway implementation. Emergency department length of stay was
      similar (253 minutes before vs 257 minutes after, P = 0.77). Computed tomography
      was used in 12.7% of visits before and 6.9% of visits after (P = 0.02). Use of
      ultrasound was not significantly different (47.3% vs 53.7%). Admission rates were
      not significantly different (45.5% vs 42.7%). CONCLUSIONS: The low-risk criteria
      had good sensitivity in ruling out appendicitis. The high-risk criteria could be
      used to guide referral or admission. Neither outperformed the a priori judgment
      of experienced providers.

PMID- 24076608
TI  - Accuracy of laceration length estimation in a pediatric emergency department and
      its impact on billing practices.
AB  - OBJECTIVES: This study aimed to determine the accuracy of laceration length
      estimation in a pediatric emergency department among health care providers of
      varying levels of training and its impact on billing practices. METHODS: This
      study involves a prospective case series. Children younger than 21 years with
      lacerations evaluated and repaired in the pediatric emergency department between
      January 1 and April 30, 2012, were eligible for enrollment. Each laceration was
      evaluated by a trainee/midlevel provider (frontline provider) and by an attending
      physician; each one offered an estimated laceration length. The true measurement
      was then documented by 1 of 6 pediatric emergency medicine fellows on shift. Data
      were analyzed using descriptive statistics. The mean error of estimation (the
      absolute differences between the estimated and the true laceration length) of
      attending physicians and frontline providers were determined and compared. The
      proportions of lacerations whose estimated length was in a different billing
      category were compared using chi(2). Cost analysis was documented. RESULTS: One
      hundred ninety patients were enrolled. The mean age was 5.9 years. A total of 119
      patients (62.6%) were male, and 134 lacerations (70.5%) were located on the face.
      Most repairs were simple (79%). There was no difference between the estimated and
      measured length among attendings and frontline providers (P = 0.583). An average
      of 8.2% of lacerations were misclassified and billed incorrectly with 20% (4/20)
      of facial lacerations up-coded. The mean overcharge was $12.04. Of 11 lacerations
      elsewhere on the body, 3 (27%) were down-coded, with an average difference of
      $6.97 for simple and $38.51 for layered repairs. CONCLUSIONS: Pediatric emergency
      medicine practitioners are accurate estimators of laceration length. Eight
      percent of lacerations are misclassified and billed incorrectly. Physicians
      should be required to report measured lengths for billing.

PMID- 24076609
TI  - Association of positive responses to suicide screening questions with hospital
      admission and repeated emergency department visits in children and adolescents.
AB  - OBJECTIVES: Although validated suicide screening tools exist for use among
      children and adolescents presenting to emergency departments (EDs), the
      associations between screening positive for suicide risk and immediate
      psychiatric hospital admission or subsequent ED use, stratified by age, have not
      been examined. METHODS: This is a retrospective cohort study of a consecutive
      case series of patients aged 8 to 18 years presenting with psychiatric chief
      complaints during a 9-month period to a single urban tertiary care pediatric ED.
      Eligible patients were administered a subset of questions from the Risk of
      Suicide Questionnaire. Outcomes included the odds of psychiatric hospitalization
      at the index visit and repeated ED visits for psychiatric complaints within the
      following year, stratified by age. RESULTS: Of the 568 patients presenting during
      the study period, responses to suicide screening questions were available for 442
      patients (78%). A total of 159 (36%) of 442 were hospitalized and 130 (29%) of
      442 had 1 or more ED visits within the following year. The proportion of patients
      providing positive responses to 1 or more suicide screening questions did not
      differ between patients aged 8 to 12 years and those aged 13 to 18 years (77/154
      [50%] vs 137/288 [48%], P = 0.63). A positive response to 1 or more of the
      questions was significantly associated with increased odds of psychiatric
      hospitalization in the older age group [adjusted odds ratio, 3.82; 95% confidence
      interval, 2.24-6.54) and with repeated visits to the ED in the younger age group
      (adjusted odds ratio, 3.55 95% confidence interval, 1.68-7.50). CONCLUSIONS:
      Positive responses to suicide screening questions were associated with acute
      psychiatric hospitalization and repeated ED visits. Suicide screening in a
      pediatric ED may identify children and adolescents with increased need of
      psychiatric resources.

PMID- 24076610
TI  - Emergency department conditions associated with the number of patients who leave
      a pediatric emergency department before physician assessment.
AB  - OBJECTIVES: As emergency department (ED) waiting times and volumes increase,
      substantial numbers of patients leave without being seen (LWBS) by a physician.
      The objective of this study was to identify ED conditions reflecting patient
      input, throughput, and output associated with the number of patients who LWBS in
      a pediatric setting. METHODS: This study was a retrospective, descriptive study
      using data from 1 urban, tertiary care pediatric ED. The study population
      consisted of all patient visits to the ED from April 2005 to March 2007.
      Multivariate Poisson regression analyses were used to examine the impact of the
      timing of patient arrival and ED conditions including patient acuity, volume, and
      waiting times on the number of patients who LWBS. RESULTS: During the study
      period, there were 138,361 patient visits corresponding to 2190 consecutive
      shifts; 11,055 patients (8%) left without being seen by a physician.In the
      multivariate analysis, the throughput variables, time from triage to physician
      assessment (rate ratio, 2.11; 95% confidence interval, 2.01-2.21), and time from
      registration to triage (rate ratio, 1.55; 95% confidence interval, 1.25-1.90) had
      the largest association with the number of patients who LWBS. CONCLUSIONS: In the
      study ED, throughput variables played a more important role than input or output
      variables on the number of patients who LWBS. This finding, which contrasts with
      a work done previously in an ED serving primarily adults, highlights the
      importance of pediatric specific research on the impacts of increasing ED waiting
      times and volumes.

PMID- 24076611
TI  - Emergency department crowding and younger age are associated with delayed
      corticosteroid administration to children with acute asthma.
AB  - OBJECTIVE: This study aimed to identify factors associated with delayed or
      omission of indicated steroids for children seen in the emergency department (ED)
      for moderate-to-severe asthma exacerbation. METHODS: This was a retrospective
      study of pediatric (age <= 21 years) patients treated in a general academic ED
      from January 2006 to September 2011 with a primary diagnosis of asthma
      (International Classification of Diseases, Ninth Revision code 493.xx) and
      moderate-to-severe exacerbations. A moderate-to-severe exacerbation was defined
      as requiring 2 or more (or continuous) bronchodilators. We determined the
      proportion of visits in which steroids were inappropriately omitted or delayed
      (>1 hour from arrival). Multivariable logistic regression models were used to
      identify patient, physician, and system factors associated with delayed or
      omitted steroids. RESULTS: Of 1333 pediatric asthma ED visits, 817 were for
      moderate-to-severe exacerbation; 645 (79%) received steroids. Patients younger
      than 6 years (odds ratio [OR], 2.25; 95% confidence interval [CI], 1.19-4.24),
      requiring more bronchodilators (OR, 2.82; 95% CI, 2.10-3.79), initially hypoxic
      (OR, 2.78; 95% CI, 1.33-5.83), or tachypneic (OR, 1.52; 95% CI, 1.05-2.20) were
      more likely to receive steroids. Median time to steroid administration was 108
      minutes (interquartile range, 65-164 minutes). Steroid administration was delayed
      in 502 visits (78%). Patients with hypoxia (OR, 1.91; 95% CI, 1.11-3.27) or
      tachypnea (OR, 1.82; 95% CI, 1.17-2.84) were more likely to receive steroids 1
      hour or less of arrival, whereas children younger than 2 years (OR, 0.16; 95% CI,
      0.07-0.35) and those arriving during periods of higher ED volume (OR, 0.79; 95%
      CI, 0.67-0.94) were less likely to receive timely steroids. CONCLUSIONS: In this
      ED, steroids were underprescribed and frequently delayed for pediatric ED
      patients with moderate-to-severe asthma exacerbation. Greater ED volume and
      younger age are associated with delays. Interventions are needed to expedite
      steroid administration, improving adherence to National Institutes of Health
      asthma guidelines.

PMID- 24076612
TI  - Behavior changes after minor emergency procedures.
AB  - OBJECTIVES: Procedures are common in pediatric emergency departments and
      frequently cause distress from pain and/or anxiety. The objective of this study
      was to describe the incidence, types, and magnitude of long-term behavior changes
      after procedures in the emergency setting. METHODS: This is a descriptive pilot
      study to determine if children display negative behavioral changes after a minor
      emergency department procedure (abscess drainage or laceration repair). Behavior
      change was measured at 1 week by telephone follow-up using the 27-item Post
      Hospitalization Behavior Questionnaire, a well-validated instrument that measures
      behavior changes across 6 categories: general anxiety, separation anxiety,
      anxiety about sleep, eating disturbances, aggression toward authority, and
      apathy/withdrawal. Significant behavior change was defined as 5 or more negative
      behavior changes on the 27-item questionnaire. RESULTS: Twenty percent of
      children who underwent abscess drainage (n = 30) and 20% who underwent laceration
      repair (n = 30) displayed significant negative behavior change at 1 week.
      Children who displayed significant negative behavior change tended to be younger
      (3.6 vs 5.9 years) and trended toward being more likely to have received
      anxiolysis or sedation (16.7% vs 8.3%). Separation anxiety, sleep difficulties,
      and aggression toward authority were the most common behavior changes.
      CONCLUSIONS: In this pilot study, a significant percentage of children undergoing
      common emergency procedures exhibited an appreciable burden of negative behavior
      change at 1 week; these results demonstrate the need for further rigorous
      investigation of predictors of these changes and interventions, which can
      ameliorate these changes.

PMID- 24076613
TI  - Energy drink and other substance use among adolescent and young adult emergency
      department patients.
AB  - OBJECTIVE: This study aimed to understand current patterns of energy drink use
      and compare the extent of usage of energy drinks and other commonly used and
      misused substances between adolescent (13-17-years-old) and young adult (18-25
      years-old) emergency department (ED) patients. METHODS: During a 6-week period
      between June and August 2010, all patients presenting to an adult or pediatric ED
      were asked to complete a computer-based, anonymous questionnaire regarding use of
      energy drinks and other substances. Wilcoxon rank-sum, 2-sample tests of binomial
      proportions, Pearson chi(2) testing, and regression models were used to compare
      energy drink and substance use by age groups. RESULTS: Past 30-day energy drink
      use was greater for young adults (57.9%) than adolescents (34.9%) (P < 0.03).
      Adolescents typically consumed a mean of 1.5 and young adults a mean of 2.6
      energy drinks per day when using energy drinks and drank at most a mean of 2.4
      and 2.6 drinks per day, respectively. Among adolescents, energy drink usage was
      more common than alcohol, "street" or illicit drugs, and tobacco usage, but less
      common than caffeine product usage. For young adults, energy drink usage was more
      common than "street" or illicit drugs, but less common than caffeine use, and
      similar to tobacco and alcohol usage. Young adult energy drink users were more
      likely than young adult non-energy drink users also to use tobacco and caffeine.
      CONCLUSIONS: Energy drink use is common among ED patients. Given the high
      prevalence of energy drink use observed, emergency physicians should consider the
      involvement of energy drinks in the presentations of young people.

PMID- 24076614
TI  - Role of central metal ions in hematoporphyrin-functionalized titania in solar
      energy conversion dynamics.
AB  - In this study, we have investigated the efficacy of electron transfer processes
      in hematoporphyrin (HP) and iron hematoporphyrin ((Fe)HP) sensitized titania as
      potential materials for capturing and storing solar energy. Steady-state and
      picosecond-resolved fluorescence studies show the efficient photoinduced electron
      transfer processes in hematoporphyrin-TiO2 (HP-TiO2) and Fe(III)-hematoporphyrin
      TiO2 (Fe(III)HP-TiO2) nanohybrids, which reveal the role of central metal ions in
      electron transfer processes. The bidentate covalent attachment of HP onto TiO2
      particulates is confirmed by FTIR, Raman scattering and X-ray photoelectron
      spectroscopy (XPS) studies. The iron oxidation states and the attachment of iron
      to porphyrin through pyrrole nitrogen atoms were investigated by cyclic
      voltammetry and FTIR studies, respectively. We also investigated the potential
      application of HP-TiO2 and Fe(III)HP-TiO2 nanohybrids for the photodegradation of
      a model organic pollutant methylene blue (MB) in aqueous solution under
      wavelength dependent light irradiation. To further investigate the role of iron
      oxidation states in electron transfer processes, photocurrent measurements were
      done by using Fe(III) and Fe(II) ions in porphyrin. This work demonstrates the
      role of central metal ions in fundamental electron transfer processes in
      porphyrin sensitized titania and their implications for dye-sensitized device
      performance.

PMID- 24076615
TI  - Stern potential and Debye length measurements in dilute ionic solutions with
      electrostatic force microscopy.
AB  - We demonstrate the ability to measure Stern potential and Debye length in dilute
      ionic solution with atomic force microscopy. We develop an analytic expression
      for the second harmonic force component of the capacitive force in an ionic
      solution from the linearized Poisson-Boltzmann equation. This allows us to
      calibrate the AFM tip potential and, further, obtain the Stern potential of
      sample surfaces. In addition, the measured capacitive force is independent of van
      der Waals and double layer forces, thus providing a more accurate measure of
      Debye length. 

PMID- 24076616
TI  - A fluorine-mediated hydrothermal method to synthesize mesoporous rhombic ZnO
      nanorod arrays and their gas sensor application.
AB  - A facile fluorine-mediated hydrothermal method was developed to synthesize
      mesoporous rhombic ZnO nanorod arrays. Fluorine ions play an essential role in
      the growth process. The novel ZnO nanorod array based gas sensor showed high
      performance for ethanol detection. 

PMID- 24076617
TI  - A mouse model for HBV immunotolerance and immunotherapy.
AB  - Lack of an appropriate small animal model remains a major hurdle for studying the
      immunotolerance and immunopathogenesis induced by hepatitis B virus (HBV)
      infection. In this study, we report a mouse model with sustained HBV viremia
      after infection with a recombinant adeno-associated virus (AAV) carrying a
      replicable HBV genome (AAV/HBV). Similar to the clinical HBV carriers, the mice
      infected with AAV/HBV were sero-negative for antibodies against HBV surface
      antigen (HBsAg). Immunization with the conventional HBV vaccine in the presence
      of aluminum adjuvant failed to elicit an immune response against HBV in these
      mice. To identify a vaccine that can potentially circumvent this tolerance, the
      TLR9 agonist CpG was added to HBsAg as an adjuvant. Vaccination of mice with
      HBsAg/CpG induced not only clearance of viremia, but also strong antibody
      production and T-cell responses. Furthermore, both the DNA replication and
      protein expression of HBV were significantly reduced in the livers of AAV/HBV
      infected mice. Accordingly, AAV/HBV-infected mice may be used as a robust model
      for investigating the underlying mechanism(s) of HBV immunotolerance and for
      developing novel immunotherapies to eradicate HBV infections. 

PMID- 24076619
TI  - Accuracy of computed tomography in the prediction of extracapsular spread of
      lymph node metastases in squamous cell carcinoma of the head and neck.
AB  - IMPORTANCE: At many institutions, computed tomography with iodinated intravenous
      contrast medium is the preferred imaging modality for staging of the neck in
      squamous cell carcinoma of the head and neck. However, few studies have
      specifically assessed the diagnostic accuracy of computed tomography for
      determining the presence or absence of extracapsular spread (ECS). OBJECTIVE: To
      determine the accuracy of modern, contrast-enhanced, multidetector computed
      tomography in the diagnosis of ECS of cervical lymph node metastases from
      squamous cell carcinoma of the head and neck. DESIGN, SETTING, AND PARTICIPANTS:
      Retrospective observational study at an academic tertiary referral center among
      100 consecutive patients between May 1, 2007, and February 1, 2012, who underwent
      a lateral cervical neck dissection for squamous cell carcinoma of the head and
      neck with neck metastases of at least 1 cm in diameter on pathologic assessment.
      Exclusion criteria included malignant neoplasms other than squamous cell
      carcinoma, a delay in surgery longer than 6 weeks from the time of staging
      computed tomography, and prior treatment of the neck or recurrent disease or a
      second primary. MAIN OUTCOMES AND MEASURES: Each patient was independently
      assigned a subjective score for the presence of ECS by 2 Certificate of Added
      Qualification-certified neuroradiologists according to a 5-point scale. Receiver
      operating characteristic curves were generated, and sensitivity, specificity,
      accuracy, positive predictive value, and negative predictive value were
      calculated for each observer. RESULTS: The areas under the receiver operating
      characteristic curve for observers 1 and 2 are 0.678 (95% CI, 0.578-0.768) and
      0.621 (95% CI, 0.518-0.716), respectively. For observer 1, the positive and
      negative predictive values for the detection of ECS were 84% (95% CI, 68%-93%)
      and 49% (95% CI, 36%-62%), respectively. For observer 2, the positive and
      negative predictive values for the detection of ECS were 71% (95% CI, 57%-82%)
      and 48% (95% CI, 32%-64%), respectively. CONCLUSIONS AND RELEVANCE: Computed
      tomography cannot be used to reliably determine the presence of pathologic ECS.
      Radiologic findings suggestive of ECS should not be relied on for treatment
      planning in squamous cell carcinoma of the head and neck.

PMID- 24076620
TI  - Female zebrafish (Danio rerio) are more vulnerable than males to microcystin-LR
      exposure, without exhibiting estrogenic effects.
AB  - Microcystins (MCs) released during cyanobacterial blooms exert varied toxicity on
      fish. Up to now, the reproductive toxicity of MCs on fish has rarely been
      reported. The present study investigated the reproductive toxicity of microcystin
      LR (MC-LR) on male and female zebrafish (Danio rerio) by subchronic immersion in
      1, 5, 20 MUg/L for 30 d. After MC-LR exposure, the hatchability and the 17 beta
      estradiol (E2) concentration in gonads significantly decreased in the 20 MUg/L
      group. In the 5 and 20 MUg/L groups, the whole body vitellogenin (VTG) levels
      significantly increased in females, while considerably decreased in males. The
      VTG1 transcriptional level significantly reduced in the liver of both female and
      male treated fish. Marked histological lesions were observed in the livers,
      ovaries and testes in MC-LR treated fish. Apoptotic rate in the ovaries
      significantly increased. Significant down-regulation of Bcl-2 transcriptional
      level was found in the gonads of all MC-LR treated fish, while marked up
      regulation of Bax transcription level was determined in the 20 MUg/L female
      treatment group, but a significant down-regulation in males. Although the
      transcriptional level of caspase-3 dropped in ovaries of the 5 and 20 MUg/L
      treatment groups, the significant increase of caspase-3 activation levels in the
      ovaries and testes were detected. The present findings indicate that MC-LR
      exposure exerts diverse reproductive toxicity in zebrafish with females
      exhibiting more sensitivity than males. The present study also confirmed for the
      first time that MC-LR does not cause any estrogenic effects in adult zebrafish.

PMID- 24076621
TI  - The use of invertebrate body burdens to predict ecological effects of metal
      mixtures in mining-impacted waters.
AB  - The present study investigated whether invertebrate body burdens can be used to
      predict metal-induced effects on aquatic invertebrate communities. Total
      dissolved metal levels and four invertebrate taxa (Leuctra sp., Simuliidae,
      Rhithrogena sp. and Perlodidae) were sampled in 36 headwater streams located in
      the north-west part of England. Using the River Invertebrate Prediction and
      Classification System (RIVPACS) taxonomic completeness of invertebrate
      communities was assessed. Quantile regression was used to relate invertebrate
      body burdens to a maximum (90th quantile) ecological response, both for all
      metals separately and in mixtures. Significant relations between Cu, Zn and Pb
      burdens in Leuctra sp. (Zn, Pb), Simuliidae (Zn, Pb), Rhithrogena sp. (Cu, Zn,
      Cu+Zn) and Perlodidae (Zn) and both taxonomic completeness (O/E taxa) and
      Biological Monitoring Working Party index scores (O/E BMWP) were observed.
      Correspondingly the obtained Cu-Zn mixture model an acceptable impact of 5%
      change in taxonomic completeness is expected at Rhithrogena sp. body burdens of
      1.9MUmolg(-1) Cu (121 MUg g(-1) Cu) in case of low Zn bioavailability
      (Rhithrogena sp. Zn body burden of 2.9 MUmol g(-1) or 190 MUg g(-1)), which will
      drop to 0.30 MUmol g(-1) Cu (19.1 MUg g(-1) Cu) in case of higher Zn
      bioavailability (Zn body burden of 72.6 MUmol g(-1) or 4747 MUg g(-1)). For Zn,
      5% change in taxonomic completeness is expected at Rhithrogena sp. body burdens
      of 76.4 MUmol g(-1) Zn (4995 MUg g(-1) Zn) in case of low Cu bioavailability (Cu
      body burden of 0.19 MUmol g(-1) or 12.1 MUg g(-1)), which will drop to 6.6 MUmol
      g(-1) Zn (432 MUg g(-1) Zn) at higher Cu bioavailability (Cu body burden of 1.74
      MUmol g(-1) or 111 MUg g(-1)). Overall, the present study concludes that
      invertebrate body burdens can be used to (1) predict metal-induced ecological
      effects and (2) to derive critical burdens for the protection of aquatic
      invertebrate communities.

PMID- 24076622
TI  - Unified treatment and measurement of the spectral resolution and temporal effects
      in frequency-resolved sum-frequency generation vibrational spectroscopy (SFG-VS).
AB  - The lack of understanding of the temporal effects and the restricted ability to
      control experimental conditions in order to obtain intrinsic spectral lineshapes
      in surface sum-frequency generation vibrational spectroscopy (SFG-VS) have
      limited its applications in surface and interfacial studies. The emergence of
      high-resolution broadband sum-frequency generation vibrational spectroscopy (HR
      BB-SFG-VS) with sub-wavenumber resolution [Velarde et al., J. Chem. Phys., 2011,
      135, 241102] offers new opportunities for obtaining and understanding the
      spectral lineshapes and temporal effects in SFG-VS. Particularly, the high
      accuracy of the HR-BB-SFG-VS experimental lineshape provides detailed information
      on the complex coherent vibrational dynamics through direct spectral
      measurements. Here we present a unified formalism for the theoretical and
      experimental routes for obtaining an accurate lineshape of the SFG response.
      Then, we present a detailed analysis of a cholesterol monolayer at the air/water
      interface with higher and lower resolution SFG spectra along with their temporal
      response. With higher spectral resolution and accurate vibrational spectral
      lineshapes, it is shown that the parameters of the experimental SFG spectra can
      be used both to understand and to quantitatively reproduce the temporal effects
      in lower resolution SFG measurements. This perspective provides not only a
      unified picture but also a novel experimental approach to measuring and
      understanding the frequency-domain and time-domain SFG response of a complex
      molecular interface. 

PMID- 24076624
TI  - Nanostructure and strain in InGaN/GaN superlattices grown in GaN nanowires.
AB  - The structural properties and the strain state of InGaN/GaN superlattices
      embedded in GaN nanowires were analyzed as a function of superlattice growth
      temperature, using complementary transmission electron microscopy techniques
      supplemented by optical analysis using photoluminescence and spatially resolved
      microphotoluminescence spectroscopy. A truncated pyramidal shape was observed for
      the 4 nm thick InGaN inclusions, where their (0001-) central facet was delimited
      by six-fold {101-l} facets towards the m-plane sidewalls of the nanowires. The
      defect content of the nanowires comprised multiple basal stacking faults
      localized at the GaN base/superlattice interface, causing the formation of zinc
      blende cubic regions, and often single stacking faults at the GaN/InGaN bilayer
      interfaces. No misfit dislocations or cracks were detected in the
      heterostructure, implying a fully strained configuration. Geometrical phase
      analysis showed a rather uniform radial distribution of elastic strain in the
      (0001-) facet of the InGaN inclusions. Depending on the superlattice growth
      temperature, the elastic strain energy is partitioned among the successive
      InGaN/GaN layers in the case of low-temperature growth, while at higher
      superlattice growth temperature the in-plane tensile misfit strain of the GaN
      barriers is accommodated through restrained diffusion of indium from the
      preceding InGaN layers. The corresponding In contents of the central facet were
      estimated at 0.42 and 0.25, respectively. However, in the latter case, successful
      reproduction of the experimental electron microscopy images by image simulations
      was only feasible, allowing for a much higher occupancy of indium adatoms at
      lattice sites of the semipolar facets, compared to the invariable 25% assigned to
      the polar facet. Thus, a high complexity in indium incorporation and strain
      allocation between the different crystallographic facets of the InGaN inclusions
      is anticipated and supported by the results of photoluminescence and spatially
      resolved microphotoluminescence spectroscopy.

PMID- 24076623
TI  - In situ label-free imaging for visualizing the biotransformation of a bioactive
      polyphenol.
AB  - Although understanding the high-resolution spatial distribution of bioactive
      small molecules is indispensable for elucidating their biological or
      pharmacological effects, there has been no analytical technique that can easily
      detect the naive molecular localization in mammalian tissues. We herein present a
      novel in situ label-free imaging technique for visualizing bioactive small
      molecules, using a polyphenol. We established a 1,5-diaminonaphthalene (1,5-DAN)
      based matrix-assisted laser desorption/ionization-mass spectrometry imaging
      (MALDI-MSI) technique for visualizing epigallocatechin-3-O-gallate (EGCG), the
      major bioactive green tea polyphenol, within mammalian tissue micro-regions after
      oral dosing. Furthermore, the combination of this label-free MALDI-MSI method and
      a standard-independent metabolite identification method, an isotopic fine
      structure analysis using ultrahigh-resolution mass spectrometer, allows for the
      visualization of spatially-resolved biotransformation based on simultaneous
      mapping of EGCG and its phase II metabolites. Although this approach has
      limitations of the detection sensitivity, it will overcome the drawbacks
      associated with conventional molecular imaging techniques, and could contribute
      to biological discovery. 

PMID- 24076625
TI  - Air pollution and individual and neighborhood socioeconomic status: evidence from
      the Multi-Ethnic Study of Atherosclerosis (MESA).
AB  - BACKGROUND: Although research has shown that low socioeconomic status (SES) and
      minority communities have higher exposure to air pollution, few studies have
      simultaneously investigated the associations of individual and neighborhood SES
      with pollutants across multiple sites. OBJECTIVES: We characterized the
      distribution of ambient air pollution by both individual and neighborhood SES
      using spatial regression methods. METHODS: The study population comprised 6,140
      participants from the Multi-Ethnic Study of Atherosclerosis (MESA). Year 2000
      annual average ambient PM2.5 and NOx concentrations were calculated for each
      study participant's home address at baseline examination. We investigated
      individual and neighborhood (2000 U.S. Census tract level) SES measures
      corresponding to the domains of income, wealth, education, and occupation. We
      used a spatial intrinsic conditional autoregressive model for multivariable
      analysis and examined pooled and metropolitan area-specific models. RESULTS: A 1
      unit increase in the z-score for family income was associated with 0.03-MUg/m3
      lower PM2.5 (95% CI: -0.05, -0.01) and 0.93% lower NOx (95% CI: -1.33, -0.53)
      after adjustment for covariates. A 1-SD-unit increase in the neighborhood's
      percentage of persons with at least a high school degree was associated with 0.47
      MUg/m3 lower mean PM2.5 (95% CI: -0.55, -0.40) and 9.61% lower NOx (95% CI: 
      10.85, -8.37). Metropolitan area-specific results exhibited considerable
      heterogeneity. For example, in New York, high-SES neighborhoods were associated
      with higher concentrations of pollution. CONCLUSIONS: We found statistically
      significant associations of SES measures with predicted air pollutant
      concentrations, demonstrating the importance of accounting for neighborhood- and
      individual-level SES in air pollution health effects research.

PMID- 24076626
TI  - Clinical practice guidelines.

PMID- 24076627
TI  - Physical therapy management of congenital muscular torticollis: an evidence-based
      clinical practice guideline: from the Section on Pediatrics of the American
      Physical Therapy Association.
AB  - BACKGROUND: Congenital muscular torticollis (CMT) is an idiopathic postural
      deformity evident shortly after birth, typically characterized by lateral flexion
      of the head to one side and cervical rotation to the opposite side due to
      unilateral shortening of the sternocleidomastoid muscle. CMT may be accompanied
      by other neurological or musculoskeletal conditions. KEY POINTS: Infants with CMT
      are frequently referred to physical therapists (PTs) to treat their asymmetries.
      This evidence-based clinical practice guideline (CPG) provides guidance on which
      infants should be monitored, treated, and/or referred, and when and what PTs
      should treat. Based upon critical appraisal of literature and expert opinion, 16
      action statements for screening, examination, intervention, and follow-up are
      linked with explicit levels of evidence. The CPG addresses referral, screening,
      examination and evaluation, prognosis, first-choice and supplemental
      interventions, consultation, discharge, follow-up, suggestions for implementation
      and compliance audits, flow sheets for referral paths and classification of CMT
      severity, and research recommendations.

PMID- 24076628
TI  - Commentary on "Physical activity and motor function in children and adolescents
      with neuromuscular disorders".

PMID- 24076629
TI  - Relationship between participation in leisure time physical activities and
      aerobic fitness in children with DCD.
AB  - PURPOSE: (1) To explore participation in leisure time physical activities (LTPAs)
      in children with developmental coordination disorder (DCD) compared with children
      developing typically. (2) To examine the association between participation in
      LTPA and aerobic fitness. METHODS: Thirty-eight children with DCD (aged 7-12
      years) were age and gender matched with 38 children developing typically.
      Participation in LTPA was self-administered by using an activity questionnaire,
      and aerobic fitness was estimated using a Shuttle Run Test. RESULTS: Children
      with DCD spent significantly less time in overall, nonorganized, and vigorous
      LTPA compared with children developing typically. Aerobic fitness was
      significantly lower for children with DCD. The best model, including age, group,
      and overall LTPA, explained 46.2% of the variance in aerobic fitness.
      CONCLUSIONS: Suitable physical activities should be fostered in children with
      DCD, who have a low participation rate and aerobic fitness level.

PMID- 24076630
TI  - Commentary on "Relationship between participation in leisure time physical
      activities and aerobic fitness in children with DCD".

PMID- 24076631
TI  - Commentary on "Psychosocial outcomes of children and adolescents with early-onset
      spinal cord injury and those with spina bifida".

PMID- 24076632
TI  - Low-cost virtual reality intervention program for children with developmental
      coordination disorder: a pilot feasibility study.
AB  - PURPOSE: To explore the feasibility of using a low-cost, off-the-shelf virtual
      reality (VR) game to treat young children with developmental coordination
      disorder (DCD) and to determine the effect of this intervention on motor
      function. METHODS: Nine children, aged 4 to 6 years, referred to physical therapy
      because of suspected DCD participated in 10 game-based intervention sessions.
      OUTCOME MEASURES: Outcome measures included Movement Assessment Battery for
      Children-2 (M-ABC-2), the DCD Questionnaire (DCD-Q), the 6-minute walk test, and
      10-m walk test. RESULTS: Statistically significant changes were observed in the
      total standard score (P = .024) and the balance subscore (P = .012) of the M-ABC
      2 and in the DCD-Q (P < .05). The children seemed to be motivated and to enjoy
      the interaction with the VR environment. CONCLUSION: VR games seemed to be
      beneficial in improving the children's motor function.

PMID- 24076633
TI  - Commentary on "Low-cost virtual game intervention program for children with
      developmental coordination disorder: a pilot feasibility study".

PMID- 24076634
TI  - Hypoxia-inducible factors enhance the effector responses of CD8(+) T cells to
      persistent antigen.
AB  - Cytolytic activity by CD8(+) cytotoxic T lymphocytes (CTLs) is a powerful
      strategy for the elimination of intracellular pathogens and tumor cells. The
      destructive capacity of CTLs is progressively dampened during chronic infection,
      yet the environmental cues and molecular pathways that influence immunological
      'exhaustion' remain unclear. Here we found that CTL immunity was regulated by the
      central transcriptional response to hypoxia, which is controlled in part by
      hypoxia-inducible factors (HIFs) and the von Hippel-Lindau tumor suppressor VHL.
      Loss of VHL, the main negative regulator of HIFs, led to lethal CTL-mediated
      immunopathology during chronic infection, and VHL-deficient CTLs displayed
      enhanced control of persistent viral infection and neoplastic growth. We found
      that HIFs and oxygen influenced the expression of pivotal transcription, effector
      and costimulatory-inhibitory molecules of CTLs, which was relevant to strategies
      that promote the clearance of viruses and tumors. 

PMID- 24076637
TI  - [Updates on rickets and osteomalacia: pathogenesis and pathophysiology of
      rickets].
AB  - Rickets is a condition of inadequate mineralization of osteoid and cartilage at
      the growing ends of bones in children. In this brief review, we first explained
      the regulation of serum Ca and P concentrations to understand Rickets. Second,
      four types of sub-division of Rickets are presented ; 1) Vitamin D dysfunction
      related, 2) Phosphate deficiency-related, 3) both 1) and 2) -related, 4) others.
      Finally, as most common entities, diagnosis and treatment in vitamin D deficiency
      and inherited hypophosphatemic Rickets/Osteomalacia are described. Over
      production of Klotho and inactivating mutations of FAM20c are explained as recent
      etiologies of non-hypercaluciuric inherited hypophosphatemic
      Rickets/Osteomalacia. 

PMID- 24076636
TI  - CD1d-lipid antigen recognition by the gammadelta TCR.
AB  - The T cell repertoire comprises alphabeta and gammadelta T cell lineages.
      Although it is established how alphabeta T cell antigen receptors (TCRs) interact
      with antigen presented by antigen-presenting molecules, this is unknown for
      gammadelta TCRs. We describe a population of human Vdelta1(+) gammadelta T cells
      that exhibit autoreactivity to CD1d and provide a molecular basis for how a
      gammadelta TCR binds CD1d-alpha-galactosylceramide (alpha-GalCer). The gammadelta
      TCR docked orthogonally, over the A' pocket of CD1d, in which the Vdelta1-chain,
      and in particular the germ line-encoded CDR1delta loop, dominated interactions
      with CD1d. The TCR gamma-chain sat peripherally to the interface, with the
      CDR3gamma loop representing the principal determinant for alpha-GalCer
      specificity. Accordingly, we provide insight into how a gammadelta TCR binds
      specifically to a lipid-loaded antigen-presenting molecule. 

PMID- 24076635
TI  - Defective sphingosine 1-phosphate receptor 1 (S1P1) phosphorylation exacerbates
      TH17-mediated autoimmune neuroinflammation.
AB  - Sphingosine 1-phosphate (S1P) signaling regulates lymphocyte egress from lymphoid
      organs into systemic circulation. The sphingosine phosphate receptor 1 (S1P1)
      agonist FTY-720 (Gilenya) arrests immune trafficking and prevents multiple
      sclerosis (MS) relapses. However, alternative mechanisms of S1P-S1P1 signaling
      have been reported. Phosphoproteomic analysis of MS brain lesions revealed S1P1
      phosphorylation on S351, a residue crucial for receptor internalization. Mutant
      mice harboring an S1pr1 gene encoding phosphorylation-deficient receptors
      (S1P1(S5A)) developed severe experimental autoimmune encephalomyelitis (EAE) due
      to autoimmunity mediated by interleukin 17 (IL-17)-producing helper T cells (TH17
      cells) in the peripheral immune and nervous system. S1P1 directly activated the
      Jak-STAT3 signal-transduction pathway via IL-6. Impaired S1P1 phosphorylation
      enhances TH17 polarization and exacerbates autoimmune neuroinflammation. These
      mechanisms may be pathogenic in MS. 

PMID- 24076638
TI  - [Updates on rickets and osteomalacia: etiology and pathophysiology of
      osteomalacia].
AB  - Impairment of bone mineralization causes rickets and osteomalacia. Rickets
      develops with impaired mineralization of bone prior to epiphyseal closure, and so
      does osteomalacia after the closure of epiphyses. Pain in lower extremities and
      back and bone pain are usually observed in patients with osteomalacia. Chronic
      hypophosphatemia and/or impairment of vitamin D action are involved in the
      development of osteomalacia. It is of great importance to suspect osteomalacia
      from clinical symptoms and laboratory data, such as hypophosphatemia and/or high
      serum alkaline phosphatase level. 

PMID- 24076639
TI  - [Updates on rickets and osteomalacia: guidelines for diagnosis of rickets and
      osteomalacia].
AB  - Rickets and osteomalacia are disorders of calcification characterized by defects
      of bone and cartilage mineralization during growth, and bone mineralization in
      adults, respectively. The specific x-ray findings including a cupping, flaring,
      and fraying of metaphysis and the elevation of the level of serum alkaline
      phosphatase are essential for the diagnosis of rickets. In addition,
      hypophosphatemia, hypocalcemia, and some symptoms including born deformity,
      spinal curvature, craniotabes, enlargement of the anterior fontanel, rachitic
      rosary, and joint swelling are also important. Clinicians need to consider the
      different normal ranges of the levels of serum alkaline phosphatase and phosphate
      depending on their patient's age when they diagnose their childhood patients. In
      contrast, the radiographic diagnosis of osteomalacia is difficult. The
      hypophosphatemia or hypocalcemia and the elevation of serum bone alkaline
      phosphatase are essential for the diagnosis of osteomalacia. Moreover, some
      clinical features including muscle weakness and bone pain, the decrease of bone
      density, and the finding of multiple uptake in bone scintigraphy or of the
      pseudofracture in bone x-ray study are also important. It is very useful for the
      differential diagnosis to measure the serum levels of 25-hydroxy vitamin D and
      fibroblast growth factor 23. 

PMID- 24076640
TI  - [Updates on rickets and osteomalacia: FGF23-mediated hypophosphatemic
      rickets/osteomalacia].
AB  - Some of the hypophosphatemic rickets/osteomalacia are caused by the increased
      bioactivity of FGF23, and classified into FGF23-mediated hypophosphatemic
      rickets/osteomalacia. This group includes various disorders such as X-linked,
      autosomal dominant and autosomal recessive hypophosphatemic rickets/osteomalacia,
      tumor-induced osteomalacia, and rickets/osteomalacia caused by the administration
      of iron polymaltose or saccharated ferric oxide. Measurement of serum levels of
      FGF23 is useful for diagnosis of these conditions. In the adult patients with
      FGF23-mediated hypophosphatemic rickets/osteomalacia, mineralizing enthesoopathy
      is an often observed complication. 

PMID- 24076641
TI  - [Updates on rickets and osteomalacia: vitamin D dependency].
AB  - Vitamin D dependency was first termed for patients resembling vitamin D
      deficiency but require high doses of vitamin D administration. Now this disease
      is known to be caused by defective conversion of 25OHD to 1,25 (OH) 2D, which is
      termed vitamin D-dependent rickets type 1 or 1alpha-hydroxylase deficiency, or by
      end-organ unresponsiveness to 1,25 (OH) 2D, which is called vitamin D-dependent
      rickets type 2 or hereditary vitamin D-resistant rickets. Recent advance in the
      molecular analysis of these diseases revealed variety in the presentation and in
      the inheritance patterns. Molecular diagnosis would be preferable for some
      atypical cases for adequate therapy. 

PMID- 24076642
TI  - [Updates on rickets and osteomalacia: the role of NaPi-2c/SLC34A3 and
      hypophosphataemic rickets].
AB  - Hereditary hypophosphatemic rickets with hypercalciuria (HHRH) , an autosomal
      recessive disorder first identified in a large Bedouin tribe, is characterized by
      hypophosphatemia secondary to renal inorganic phosphate (Pi) wasting, resulting
      in increased serum1,25-dihydroxyvitamin D3 concentrations with associated
      intestinal calcium hyperabsorption, hypercalciuria, rickets, and osteomalacia.
      Recent studies identified several mutations in the NaPi-2c/NPT2c transporter gene
      (SLC34A3) as the cause of HHRH. The fact that HHRH is caused by NaPi-2c loss-of
      function mutations is compatible with the HHRH phenotype and the prevailing view
      of renal Pi regulation. The NaPi-2c mutants in HHRH show defective processing and
      stability. 

PMID- 24076643
TI  - [Updates on rickets and osteomalacia: biological function of osteocyte and
      FGF23/klotho system].
AB  - Osteocytes are known to synthesize FGF23 which would bind to FGFR1c/klotho
      complex in proximal renal tubules in kidney, thereby, reducing serum
      concentration of Pi and the activity of 1alpha-hydroxylase. Meanwhile, recent
      studies suggest the possibility that osteocytes might induce osteolysis of lacuna
      walls. Compact, cortical bone develops well-organized distribution of osteocyte
      lacunar canalicular system (OLCS) , which appears to be efficient for osteocytic
      function. There seems some relation between the geometrical regularity of OLCS
      and osteocytic regulation of systemic and local mineral balance. 

PMID- 24076644
TI  - [Updates on rickets and osteomalacia: mechanism and regulation of bone
      mineralization].
AB  - Bone is mineralized when hydroxyapatite crystals derived from calcium ions and
      inorganic phosphate (Pi) grow along collagen fibrils in the extracellular matrix.
      Mineralization is initiated by nucleation of those crystals. Mature osteoblasts
      secrete matrix vesicles into osteoid, which contain growing hydroxyapatite
      crystal seeds. After rupture of the lipid bilayer of those vesicles, crystals
      continue to grow as a mineralized nodule and adhere to collagen fibrils. It
      remains controversial whether nucleation occurs mainly in matrix vesicles or also
      extra-vesicularly around collagen fibrils. Mineralization is inhibited by
      pyrophosphate (PPi) and by SIBLING family proteins, which carry an acidic serine-
      and aspartate-rich motif (ASARM) and include osteopontin, dentin matrix protein 1
      and MEPE. Intracellular and extracellular activity of these factors is regulated
      by the PPi-generating ectonucleotide pyrophosphatase/phosphodiesterase (ENPP1) ,
      the PPi-transporter progressive ankylosis (ANK) protein, the PPi-degrading/Pi
      generating ectoenzyme alkaline phosphatase (ALPL, TNAP) , and PHEX endopeptidase.
      Gain- or loss-of-function mutations in genes encoding these proteins are
      associated with mineralization disorders such as ectopic calcification and other
      pathologies. 

PMID- 24076645
TI  - [Updates on rickets and osteomalacia: anti-FGF23 antibody, a new therapeutic
      approach for hypophosphatemic rickets/osteomalacia].
AB  - In the last decade, Fibroblast growth factor (FGF) 23 has been shown to be a
      causative factor of hypophosphatemic rickets/osteomalacia, and considered as
      potential therapeutic target for this disease. Now the most attention is paid to
      FGF23 blockades as a new category of therapy that may replace the current
      supplementation of phosphate and active vitamin D. In this chapter,
      pharmacological actions of the FGF23-neutralizing antibodies in murine
      hypophosphatemic rickets/osteomalacia model are reviewed. In addition, other
      types of FGF23 blockades are also briefly discussed. 

PMID- 24076646
TI  - [Updates on rickets and osteomalacia: various roles of Klotho and FGF23 in vivo
      ].
AB  - Recent understandings of phosphate regulation have, at least in part, depended
      upon the findings of fibroblast growth factor (FGF) 23, the hormone specific for
      phosphate regulation. Moreover, FGF23 would be the most important marker for
      prognosis in chronic kidney disease (CKD) . On the other hand, Klotho was firstly
      developed as a responsible gene for senescence. Although the role of Klotho has
      been so far established as a co-receptor for FGF23 in mineral metabolism, Klotho
      would play rather various roles than FGF23 signaling. Thus Klotho is not
      necessarily equivalent to FGF23. Further studies for both Klotho and FGF23 will
      elucidate to understand mineral homeostasis. 

PMID- 24076647
TI  - [Updates on rickets and osteomalacia: vitamin D deficiency : its pathophysiology
      and treatment].
AB  - Vitamin D deficiency is a common cause of rickets/osteomalacia. Milder decrease
      in vitamin D store, vitamin D insufficiency, does not lead to clinical
      rickets/osoteomalacia but could result in mineralization defect and an increased
      fracture risk. Vitamin D store is easily assessed by serum 25 (OH) D
      concentration : less than 20 ng/mL is generally considered vitamin D deficiency
      whereas between 20 and 30 ng/mL vitamin D insufficiency. In the management of
      bone and mineral disorders including rickets/osteomalacia, it is a common
      practice in many countries to measure serum 25 (OH) D, and if
      deficiency/insufficiency is present, which would be corrected by native vitamin
      D. However, in Japan, serum 25 (OH) D is not routinely measured because it is not
      covered by national health insurance policy, thus vitamin D
      deficiency/insufficiency is often overlooked and even misdiagnosed. There has
      been no native vitamin D that can be prescribed in Japan, thus patients with
      vitamin D deficiency/insufficiency have been prescribed active instead of native
      vitamin D. These circumstances must be changed to increase the awareness of
      vitamin D deficiency/insufficiency. 

PMID- 24076648
TI  - [Updates on rickets and osteomalacia: the therapy for FGF23 related rickets].
AB  - FGF23 related rickets/osteomalacia was mainly composed of XLH, ADHR, ARHR1, ARHR2
      and tumor induced rickets/osteomalacia. Although the mechanism for increasing
      serum FGF23 levels was different from disease to disease, therapies for these
      patients were basically the same ; pharmacological doses of active vitamin D and
      phosphate administration. It is noted that phosphate therapy is associated with
      the occurrence of secondary hyperparathyroidism and nephrocalcinosis. Moreover,
      recent evidences indicated that these combination therapies increased serum FGF23
      levels. On the basis of these data, it is suggested that appropriate doses of
      active vitamin D and phosphate are to be selected according to the data of serum
      PTH, ALP and the amount of urinary excretion of calcium. For the children, the
      recovery of growth velocity is also an important factor for deciding the suitable
      doses of the therapies. 

PMID- 24076649
TI  - [Updates on rickets and osteomalacia. dental diseases in rickets].
AB  - Rickets is characterized by mineralization defect in bone and cartilage. X-linked
      hypophosphatemic rickets (XLH) is the most common form of inherited rickets.
      Mineralization defect is observed in dentin as well as in bone and cartilage in
      XLH. The dominant feature is the occurrence of infectious periradicular abscesses
      on deciduous and permanent teeth, not associated with trauma or decay. Dental
      care including the maintenance of good oral hygiene and periodical examinations
      should be performed. A preventive sealing of occlusal surfaces can be considered.
      Endodontic treatment or extraction are carried out in the presence of
      periradicular abscesses. Further studies are necessary for elucidating mechanisms
      of dentin mineralization defect and the occurrence of periradicular abscesses and
      for developing preventive and curative measures in XLH. 

PMID- 24076650
TI  - [Updates on rickets and osteomalacia: surgical treatment for
      rickets/osteomalacia].
AB  - In general, surgical treatments are indicated for severe extremity deformities
      due to impaired bone growth and fractures due to bone fragility in
      rickets/osteomalacia patients. Corrective osteotomy and fixation with external
      fixators, Kirshner's wires, intramedullary nail, plates and casting including
      epiphysiodesis is performed. For tumor induced osteomalacia patients, excision of
      causative tumor is indispensable as definitive therapy. In this article, surgical
      treatments were updated especially for tumor induced osteomalacia. 

PMID- 24076651
TI  - It cuts two ways: microtubule loss during Alzheimer disease.

PMID- 24076652
TI  - Usp16: key controller of stem cells in Down syndrome.

PMID- 24076653
TI  - CDC42 switches IRSp53 from inhibition of actin growth to elongation by clustering
      of VASP.
AB  - Filopodia explore the environment, sensing soluble and mechanical cues during
      directional motility and tissue morphogenesis. How filopodia are initiated and
      spatially restricted to specific sites on the plasma membrane is still unclear.
      Here, we show that the membrane deforming and curvature sensing IRSp53 (Insulin
      Receptor Substrate of 53 kDa) protein slows down actin filament barbed end
      growth. This inhibition is relieved by CDC42 and counteracted by VASP, which also
      binds to IRSp53. The VASP:IRSp53 interaction is regulated by activated CDC42 and
      promotes high-density clustering of VASP, which is required for processive actin
      filament elongation. The interaction also mediates VASP recruitment to liposomes.
      In cells, IRSp53 and VASP accumulate at discrete foci at the leading edge, where
      filopodia are initiated. Genetic removal of IRSp53 impairs the formation of VASP
      foci, filopodia and chemotactic motility, while IRSp53 null mice display
      defective wound healing. Thus, IRSp53 dampens barbed end growth. CDC42 activation
      inhibits this activity and promotes IRSp53-dependent recruitment and clustering
      of VASP to drive actin assembly. These events result in spatial restriction of
      VASP filament elongation for initiation of filopodia during cell migration,
      invasion, and tissue repair. 

PMID- 24076654
TI  - microRNA-17-92 cluster is a direct Nanog target and controls neural stem cell
      through Trp53inp1.
AB  - The transcription factor Nanog plays a critical role in the self-renewal of
      embryonic stem cells as well as in neural stem cells (NSCs). microRNAs (miRNAs)
      are also involved in stemness regulation. However, the miRNA network downstream
      of Nanog is still poorly understood. High-throughput screening of miRNA
      expression profiles in response to modulated levels of Nanog in postnatal NSCs
      identifies miR-17-92 cluster as a direct target of Nanog. Nanog controls miR-17
      92 cluster by binding to the upstream regulatory region and maintaining high
      levels of transcription in NSCs, whereas Nanog/promoter association and cluster
      miRNAs expression are lost alongside differentiation. The two miR-17 family
      members of miR-17-92 cluster, namely miR-17 and miR-20a, target Trp53inp1, a
      downstream component of p53 pathway. To support a functional role, the presence
      of miR-17/20a or the loss of Trp53inp1 is required for the Nanog-induced
      enhancement of self-renewal of NSCs. We unveil an arm of the Nanog/p53 pathway,
      which regulates stemness in postnatal NSCs, wherein Nanog counteracts p53 signals
      through miR-17/20a-mediated repression of Trp53inp1. 

PMID- 24076655
TI  - TRIAD1 and HHARI bind to and are activated by distinct neddylated Cullin-RING
      ligase complexes.
AB  - RING (Really Interesting New Gene)-in-between-RING (RBR) enzymes are a distinct
      class of E3 ubiquitin ligases possessing a cluster of three zinc-binding domains
      that cooperate to catalyse ubiquitin transfer. The regulation and biological
      function for most members of the RBR ligases is not known, and all RBR E3s
      characterized to date are auto-inhibited for in vitro ubiquitylation. Here, we
      show that TRIAD1 and HHARI, two members of the Ariadne subfamily ligases,
      associate with distinct neddylated Cullin-RING ligase (CRL) complexes. In
      comparison to the modest E3 ligase activity displayed by isolated TRIAD1 or
      HHARI, binding of the cognate neddylated CRL to TRIAD1 or HHARI greatly
      stimulates RBR ligase activity in vitro, as determined by auto-ubiquitylation,
      their ability to stimulate dissociation of a thioester-linked UBCH7~ubiquitin
      intermediate, and reactivity with ubiquitin-vinyl methyl ester. Moreover, genetic
      evidence shows that RBR ligase activity impacts both the levels and activities of
      neddylated CRLs in vivo. Cumulatively, our work proposes a conserved mechanism of
      CRL-induced Ariadne RBR ligase activation and further suggests a reciprocal role
      of this special class of RBRs as regulators of distinct CRLs. 

PMID- 24076657
TI  - Determination of school-related problems in children treated for cancer.
AB  - This descriptive and case-control study was carried out in a pediatric oncology
      outpatient clinic to determine the school-related physical, social, and
      psychological problems and problems experienced in academic achievement of
      children treated for cancer. The sample of the study consisted of 56 Turkish
      patients with cancer, aged 7-18 years, who were in remission and attending school
      as well as their parents, a control group of patients who did not have cancer,
      and their teachers. A Child Information Form, a Child Health Questionnaire
      Parent's Form of 50 questions, a Behavior Evaluation Scale for Children, and
      Young People and a Teacher's Report Form were used as data collection tools in
      the study. Of the children, 30.3% experienced various physical difficulties
      stemming from cancer therapy that affected their school life. The number of late
      enrollments, the number of children repeating a grade, and the rates of school
      absenteeism were also found to be higher in the survivors than in the controls. 

PMID- 24076658
TI  - Critical care paramedics in England: a national survey of ambulance services.
AB  - Critical care paramedics (CCPs) have been introduced by individual ambulance
      trusts in England, but there is a lack of national coordination of training and
      practice. We conducted an online survey of NHS ambulance services to provide an
      overview of the current utilization and role of CCPs in England. The survey found
      significant variations in training, competencies and the working patterns of the
      ~90 CCPs working in five ambulance services. All ambulance trusts currently
      employing CCPs are planning on increasing CCP numbers, whereas 'insufficient
      financial means' and 'insufficient scientific evidence' are the two major
      barriers to CCP utilization. The CCP model established in five ambulance services
      in England is unique within Europe. With increasing numbers of CCPs, concerns
      about lack of supportive scientific evidence and clinical need should be
      addressed. Optimal delivery of prehospital critical care in England remains
      controversial. 

PMID- 24076656
TI  - Endophilin, Lamellipodin, and Mena cooperate to regulate F-actin-dependent EGF
      receptor endocytosis.
AB  - The epidermal growth factor receptor (EGFR) plays an essential role during
      development and diseases including cancer. Lamellipodin (Lpd) is known to control
      lamellipodia protrusion by regulating actin filament elongation via Ena/VASP
      proteins. However, it is unknown whether this mechanism supports endocytosis of
      the EGFR. Here, we have identified a novel role for Lpd and Mena in clathrin
      mediated endocytosis (CME) of the EGFR. We have discovered that endogenous Lpd is
      in a complex with the EGFR and Lpd and Mena knockdown impairs EGFR endocytosis.
      Conversely, overexpressing Lpd substantially increases the EGFR uptake in an F
      actin-dependent manner, suggesting that F-actin polymerization is limiting for
      EGFR uptake. Furthermore, we found that Lpd directly interacts with endophilin, a
      BAR domain containing protein implicated in vesicle fission. We identified a role
      for endophilin in EGFR endocytosis, which is mediated by Lpd. Consistently, Lpd
      localizes to clathrin-coated pits (CCPs) just before vesicle scission and
      regulates vesicle scission. Our findings suggest a novel mechanism in which Lpd
      mediates EGFR endocytosis via Mena downstream of endophilin. 

PMID- 24076659
TI  - Factors associated with survival among patients with AIDS-related primary central
      nervous system lymphoma.
AB  - OBJECTIVE: AIDS-related primary central nervous system lymphoma (AR-PCNSL) has a
      poor prognosis. Improved understanding of specific patient, infectious,
      diagnostic, and treatment-related factors that affect overall survival (OS) is
      required to improve outcomes. DESIGN: Population-based registry linkage study.
      METHODS: Adult cases from the San Francisco AIDS registry (1990-2000) were
      matched with the California Cancer Registry (1985-2002) to ascertain AR-PCNSL
      data. Survival time was assessed through 31 December 2007. Risk factors and
      temporal trends for death were measured using two-sided Kaplan-Meier and Cox
      analyses. RESULTS: Two hundred and seven AR-PCNSL patients were identified: 68%
      were white, 20% Hispanic, 10% African-American, and 2% Asian. Nineteen percent of
      patients had central nervous system (CNS) opportunistic infections diagnosed
      prior to AR-PCNSL. Fifty-seven percent of patients received radiation and/or
      chemotherapy and 12% used HAART prior to or within 30 days of AR-PCNSL diagnosis.
      One hundred and ninety-nine patients died (34 deaths/100 person-years). In
      adjusted analysis, prior CNS opportunistic infection diagnosis increased risk of
      death (hazard ratio 1.9, P = 0.0006) whereas radiation and/or chemotherapy
      decreased risk (hazard ratio 0.6, P < 0.0001). AR-PCNSL diagnosis 1999-2002 had a
      lower mortality risk (hazard ratio = 0.4, P = 0.02) compared to 1990-1995.
      African-Americans had an increased risk of death compared to whites or Asians
      (hazard ratio = 2.0, P = 0.007). CONCLUSION: OS among AR-PCNSL patients improved
      over time but remains poor, especially among African-Americans. Prospective
      evaluation of curative therapy in AR-PCNSL is urgently needed. Accurate diagnosis
      of CNS mass lesions in patients with AIDS is required and for those with AR
      PCNSL, antiretroviral therapy with concomitant AR-PCNSL therapy, and
      antimicrobial supportive care may improve OS.

PMID- 24076660
TI  - Effect of antiretroviral therapy on patients' economic well being: five-year
      follow-up.
AB  - OBJECTIVE: Evaluate the effect of antiretroviral therapy (ART) on South African
      HIV patients' economic well being, as indicated by symptoms, normal activities,
      employment, and external support, during the first 5 years on treatment. METHODS:
      Prospective cohort study of 879 adult patients at public or nongovernmental
      clinics enrolled before ART initiation or on ART less than 6 months and followed
      for 5.5 years or less. Patients were interviewed during routine clinic visits.
      Outcomes were estimated using population-averaged logistic regression and
      reported as proportions of the cohort experiencing outcomes by duration on ART.
      RESULTS: For patients remaining in care, outcomes improved continuously and
      substantially, with all differences between baseline and 5 years statistically
      significant (P < 0.05) and continued significant improvement between year 3 and
      year 5. The probability of reporting pain last week fell from 69% during the
      three months before starting ART to 17% after 5 years on ART and fatigue from 62
      to 7%. The probability of not being able to perform normal activities in the
      previous week fell from 47 to 5% and of being employed increased from 32 to 44%;
      difficulty with job performance among those employed fell from 56 to 6%. As
      health improved, the probability of relying on a caretaker declined from 81 to
      less than 1%, and receipt of a disability grant, which initially increased, fell
      slightly over time on ART. CONCLUSION: Results from one of the longest
      prospective cohorts tracking economic outcomes of HIV treatment in Africa suggest
      continuous improvement during the first 5 years on treatment, confirming the
      sustained economic benefits of providing large-scale treatment.

PMID- 24076661
TI  - High attrition before and after ART initiation among youth (15-24 years of age)
      enrolled in HIV care.
AB  - OBJECTIVES: To compare pre and post-ART attrition between youth (15-24 years) and
      other patients in HIV care, and to investigate factors associated with attrition
      among youth. DESIGN: Cohort study utilizing routinely collected patient-level
      data from 160 HIV clinics in Kenya, Mozambique, Tanzania, and Rwanda. METHODS:
      Patients at least 10 years of age enrolling in HIV care between 01/05 and 09/10
      were included. Attrition (loss to follow-up or death 1 year after enrollment or
      ART initiation) was compared between youth and other patients using multivariate
      competing risk (pre-ART) and traditional (post-ART) Cox proportional hazards
      methods accounting for within-clinic correlation. Among youth, patient-level and
      clinic-level factors associated with attrition were similarly assessed. RESULTS:
      A total of 312,335 patients at least 10 years of age enrolled in HIV care;
      147,936 (47%) initiated ART, 17% enrolling in care and 10% initiating ART were
      youth. Attrition before and after ART initiation was substantially higher among
      youth compared with other age groups. Among youth, nonpregnant women experienced
      lower pre-ART attrition than men [sub-division hazard ratio = 0.90, 95%
      confidence interval (CI): 0.86-0.94], while both pregnant [adjusted hazard ratio
      (AHR) = 0.85, 95% CI: 0.74-0.97] and nonpregnant (AHR = 0.79, 95% CI: 0.73-0.86)
      female youth experienced lower post-ART attrition than men. Youth attending
      clinics providing sexual and reproductive health services including condoms (AHR
      = 0.47, 95% CI: 0.32-0.70) and clinics offering adolescent support groups (AHR =
      0.73, 95% CI: 0.52-1.0) experienced significantly lower attrition after ART
      initiation. CONCLUSION: Youth experienced substantially higher attrition before
      and after ART initiation compared with younger adolescents and older adults.
      Adolescent-friendly services were associated with reduced attrition among youth,
      particularly after ART initiation.

PMID- 24076662
TI  - 3D aligned-carbon-nanotubes@Li2FeSiO4 arrays as high rate capability cathodes for
      Li-ion batteries.
AB  - 3D aligned-carbon-nanotubes (ACNTs)@Li2FeSiO4 nanocomposite arrays on Al foil
      were developed as cathode materials for Li-ion batteries. The ACNTs were grown
      directly on an Al foil by a chemical vapor deposition method to achieve a 3D
      current collector structure for direct charge transport. Li2FeSiO4 nanoparticles
      were deposited on the surface of the ACNTs by a polyvinylalcohol (PVA)-assisted
      sol-gel method. The 3D samples showed a high degree of alignment of nanotubes
      with a favorable pore morphology before and after cycling. According to
      electrochemical measurements, the 3D sample with optimized mass ratio of ACNTs
      and Li2FeSiO4 (2:1) showed excellent rate capability and capacity retention,
      delivering a discharge specific capacity of 142 mAh g(-1) at a rate of 0.5 C (C =
      160 mAg(-1)) and maintaining 99% of the initial discharge capacity after 50
      cycles at 24  degrees  C. Up to 20 C, the delivered charge/discharge capacity was
      94 mAh g(-1) after 172 cycles, which is 54% of the value obtained at C/20 (175
      mAh g(-1)). In comparison, carbon coated nanoporous Li2FeSiO4 obtained under
      analogous conditions by a PVA-assisted sol-gel method can only deliver a capacity
      of 80 mAh g(-1) and showed poor rate capability. In addition, despite
      amorphization, dissolution and chemical composition changes occurring in the 3D
      samples upon extended cycling, the 3D samples showed good long-term cycling
      stability at a high current density (5 C), maintaining ~80% of the initial
      discharge capacity after 1000 cycles and ~70% after 2000 cycles.

PMID- 24076663
TI  - Metabolic characterization of a Sirt5 deficient mouse model.
AB  - Sirt5, localized in the mitochondria, is a member of sirtuin family of NAD+
      dependent deacetylases. Sirt5 was shown to deacetylate and activate carbamoyl
      phosphate synthase 1. Most recently, Sirt5 was reported to be the predominant
      protein desuccinylase and demalonylase in the mitochondria because the ablation
      of Sirt5 enhanced the global succinylation and malonylation of mitochondrial
      proteins, including many metabolic enzymes. In order to determine the
      physiological role of Sirt5 in metabolic homeostasis, we generated a germline
      Sirt5 deficient (Sirt5-/-) mouse model and performed a thorough metabolic
      characterization of this mouse line. Although a global protein hypersuccinylation
      and elevated serum ammonia during fasting were observed in our Sirt5-/- mouse
      model, Sirt5 deficiency did not lead to any overt metabolic abnormalities under
      either chow or high fat diet conditions. These observations suggest that Sirt5 is
      likely to be dispensable for the metabolic homeostasis under the basal
      conditions.

PMID- 24076666
TI  - Subfascial harvest of the extended latissimus dorsi myocutaneous flap in breast
      reconstruction: a comparative analysis of two techniques.
AB  - BACKGROUND: Widespread adoption of the extended latissimus dorsi myocutaneous
      flap in breast reconstruction has been limited by donor-site complications. The
      dissection plane may be either above or below the superficial layer of the
      thoracolumbar fascia, which may be transferred with the flap or retained on the
      back skin flaps. The aim of this study was to investigate whether varying the
      plane of dissection improves donor-site morbidity and complications. METHODS: A
      comparative analysis of consecutive women treated with extended latissimus dorsi
      myocutaneous breast reconstruction by a single surgeon (D.F.) between 2006 and
      2012 was performed. RESULTS: Eighty patients were reviewed. Between 2006 and
      2011, 47 patients were treated with traditional suprafascial harvest (group A);
      the subsequent 33 patients between 2011 and 2012 had subfascial harvest (group
      B), retaining the superficial fascia on the back skin flaps. When compared with
      group A, group B patients showed significant reduction in both mean number of
      seroma drainage events (p = 0.027) and mean total aspirated seroma volume, which
      was reduced by half (p = 0.006). Group B patients also reported significant
      reduction in donor-site pain (p = 0.041) and donor-site scar adherence to the
      chest wall (p = 0.026). No increases in flap or donor-site dehiscence, partial
      flap loss, or other minor or major complications were observed. CONCLUSION: The
      technique of subfascial harvest during autologous latissimus dorsi flap breast
      reconstruction significantly improves back donor-site morbidity without
      compromising flap survival. CLINICAL QUESTION/LEVEL OF EVIDENCE: Therapeutic,
      III.

PMID- 24076664
TI  - Activation of Hedgehog signaling by loss of GNAS causes heterotopic ossification.
AB  - Heterotopic ossification, the pathologic formation of extraskeletal bone, occurs
      as a common complication of trauma or in genetic disorders and can be disabling
      and lethal. However, the underlying molecular mechanisms are largely unknown.
      Here we demonstrate that Galphas restricts bone formation to the skeleton by
      inhibiting Hedgehog signaling in mesenchymal progenitor cells. In progressive
      osseous heteroplasia, a human disease caused by null mutations in GNAS, which
      encodes Galphas, Hedgehog signaling is upregulated in ectopic osteoblasts and
      progenitor cells. In animal models, we show that genetically-mediated ectopic
      Hedgehog signaling is sufficient to induce heterotopic ossification, whereas
      inhibition of this signaling pathway by genetic or pharmacological means strongly
      reduces the severity of this condition. As our previous work has shown that GNAS
      gain-of-function mutations upregulate WNT-beta-catenin signaling in osteoblast
      progenitor cells, resulting in their defective differentiation and fibrous
      dysplasia, we identify Galphas as a key regulator of proper osteoblast
      differentiation through its maintenance of a balance between the Wnt-beta-catenin
      and Hedgehog pathways. Also, given the results here of the pharmacological
      studies in our mouse model, we propose that Hedgehog inhibitors currently used in
      the clinic for other conditions, such as cancer, may possibly be repurposed for
      treating heterotopic ossification and other diseases caused by GNAS inactivation.

PMID- 24076665
TI  - Coordinate activation of Shh and PI3K signaling in PTEN-deficient glioblastoma:
      new therapeutic opportunities.
AB  - In glioblastoma, phosphatidylinositol 3-kinase (PI3K) signaling is frequently
      activated by loss of the tumor suppressor phosphatase and tensin homolog (PTEN).
      However, it is not known whether inhibiting PI3K represents a selective and
      effective approach for treatment. We interrogated large databases and found that
      sonic hedgehog (SHH) signaling is activated in PTEN-deficient glioblastoma. We
      demonstrate that the SHH and PI3K pathways synergize to promote tumor growth and
      viability in human PTEN-deficient glioblastomas. A combination of PI3K and SHH
      signaling inhibitors not only suppressed the activation of both pathways but also
      abrogated S6 kinase (S6K) signaling. Accordingly, targeting both pathways
      simultaneously resulted in mitotic catastrophe and tumor apoptosis and markedly
      reduced the growth of PTEN-deficient glioblastomas in vitro and in vivo. The
      drugs tested here appear to be safe in humans; therefore, this combination may
      provide a new targeted treatment for glioblastoma. 

PMID- 24076667
TI  - Breast reconstruction in the morbidly obese patient: assessment of 30-day
      complications using the 2005 to 2010 National Surgical Quality Improvement
      Program data sets.
AB  - BACKGROUND: The authors assess the risk and safety profiles of both implant and
      autologous breast reconstructions in the morbidly obese population using the
      National Surgical Quality Improvement Program data sets. METHODS: The authors
      reviewed the 2005 to 2010 National Surgical Quality Improvement Program
      databases, identifying encounters for Current Procedural Terminology codes
      including either implant-based reconstruction or autologous reconstruction.
      Patients were classified and compared based on World Health Organization obesity
      criteria. Complications were divided into three categories: major surgical
      complications, wound complications, and medical complications. RESULTS: During
      the study period, 15,937 breast reconstructions were identified. The incidence of
      obesity was 27.1 percent, with 4.0 percent defined as class III (morbidly) obese.
      Morbidly obese patients had significantly higher rates of almost all
      complications compared with nonobese patients, including major surgical
      complications (p < 0.001), medical complications (p < 0.001), respiratory
      complications (p = 0.015), venous thromboembolism (p = 0.001), and wound
      complications (p < 0.001). These patients also were more likely to require a
      return to the operating room both for any reason (p < 0.001) and specifically for
      prosthesis/flap failure (p < 0.001). Morbid obesity was found to be an
      independent predictor of wound complications (OR, 2.1; p < 0.001), surgical
      complications (OR, 1.6; p < 0.001), medical complications (OR, 1.6; p = 0.01),
      and return to the operating room (OR, 1.5; p < 0.001). There was no significant
      difference in the 30-day surgical complication rates between implant and
      autologous reconstructions in the morbidly obese (p = 0.23). CONCLUSION: Morbid
      obesity is associated with a significantly increased risk of perioperative
      complications that translates into progressive, higher rates of overall
      morbidity, regardless of reconstructive modality. CLINICAL QUESTION/LEVEL OF
      EVIDENCE: Risk, II.

PMID- 24076668
TI  - Demystifying the use of internal mammary vessels as recipient vessels in free
      flap breast reconstruction.
AB  - BACKGROUND: The internal mammary vessels are commonly used as primary recipient
      vessels for free flap breast reconstruction. However, there is debate about the
      reliability of the left internal mammary vein. The authors explored the anatomy
      of the internal mammary vessels as revealed during free flap breast
      reconstruction to determine whether microvascular complications differed between
      the left and right sides. METHODS: All free flap breast reconstructions performed
      using internal mammary recipient vessels at the authors' institution between
      January of 2000 and December of 2010 were reviewed. The authors compared left and
      right breast reconstructions for internal mammary vessel diameters and
      microvascular complications, pedicle thrombosis, and total flap losses. RESULTS:
      Overall, 1773 free flap breast reconstructions were performed in 1336 patients
      using the internal mammary vessels: 899 unilateral and 437 bilateral. The left
      side was used in 904 cases and the right side in 869 cases. Although the mean
      sizes of the left and right internal mammary arteries (2.44 and 2.47 mm,
      respectively) did not differ significantly, the left vein was significantly
      smaller than the right vein (2.47 mm versus 2.93 mm; p = 0.038). The overall rate
      of venous thrombosis was significantly higher on the left than on the right (3.0
      percent versus 2.3 percent; p = 0.028). The rates of flap loss in left and right
      breast reconstructions did not differ significantly (1.9 percent versus 2.2
      percent). CONCLUSION: Although the left internal mammary vein is smaller than the
      right and is at higher risk for venous complications, it remains an acceptable
      recipient vessel for free flap breast reconstruction. CLINICAL QUESTION/LEVEL OF
      EVIDENCE: Therapeutic, III.

PMID- 24076669
TI  - Discussion: Frequency of the preoperative flaws and commonly required maneuvers
      to correct them: a guide to reducing the revision rhinoplasty rate.

PMID- 24076670
TI  - Anatomical study of the medial crura and the effect on nasal tip projection in
      open rhinoplasty.
AB  - BACKGROUND: Common variations in morphology of the medial crura have been
      described. The authors' observation is that changes in nasal tip projection
      depend on the shape and strength of the medial crura. The authors investigated
      how differences in medial crura shape affect tip projection after surgical
      intervention. METHODS: Seventeen cadaver heads were dissected with an open
      rhinoplasty approach. Nasal tip projection and columellar length and width were
      measured. Medial crura shape was noted and classified. Anthropometric
      measurements were made preoperatively and after each of the following procedures:
      (1) elevation of skin envelope and closure of the columellar incision, (2)
      interdomal and medial crural sutures, and (3) placement and fixation of a
      floating columellar strut. RESULTS: Three anatomical variations of the medial
      crura were noted: type 1, asymmetric parallel (n = 7); type 2, flared symmetric
      (n = 5); and type 3, straight symmetric (n = 5). A significant difference in tip
      projection after elevation of the skin envelope and closure was discovered
      between types 1 and 3 (p = 0.004). Type 2 medial crura were found to have a mean
      reduction of 1.0 mm. Suture techniques resulted in return to baseline tip
      projection for types 1 and 2. Columellar strut placement increased tip projection
      in all types. CONCLUSIONS: Changes in tip projection after an open rhinoplasty
      depend on the shape of the medial crura. Straight symmetric (type 3) cartilages
      can maintain tip projection without any additional intervention during an open
      rhinoplasty. Asymmetric parallel (type 1) or flared symmetric (type 2) variants
      will require interdomal and medial crural sutures to maintain baseline tip
      projection.

PMID- 24076671
TI  - Discussion: Anatomical study of the medial crura and the effect on nasal tip
      projection in open rhinoplasty.

PMID- 24076672
TI  - Tear trough and palpebromalar groove in young versus elderly adults: a sectional
      anatomy study.
AB  - BACKGROUND: The tear trough and palpebromalar groove are of increasing interest
      to plastic surgeons, but their mechanisms of formation remain unclear. This study
      evaluated the anatomical foundation for tear trough and palpebromalar groove.
      METHODS: Sagittal dissection and layered dissection were performed on 20 elderly
      cadaveric hemifaces with obvious tear troughs and palpebromalar grooves and on 16
      young cadaveric hemifaces without obvious tear troughs and palpebromalar grooves.
      Cross-sectional specimens and tissue sections were compared between the two
      groups to identify the differences. RESULTS: The malar fat pad becomes atrophic
      and descends with aging. The orbicularis retaining ligament arose from the
      inferior orbital rim and ended at the junction of palpebral and orbital portions
      of the orbicularis oculi muscle. The ligament limited the descent of the
      orbicularis oculi muscle. The orbicularis retaining ligament continued with the
      origin of the orbicularis oculi muscle and the dense muscular attachment arose
      from the maxilla. Histologic evaluation confirmed the ligamentous features of the
      orbicularis retaining ligament. CONCLUSIONS: The orbicularis retaining ligament
      plays an important role in formation of the tear trough, and atrophy and descent
      of the malar fat pad make the tear trough and palpebromalar groove more obvious
      with aging. These findings may be of value in blepharoplasty and midfacial
      rejuvenation.

PMID- 24076673
TI  - Three-dimensional simulated images in breast augmentation surgery: an
      investigation of patients' satisfaction and the correlation between prediction
      and actual outcome.
AB  - BACKGROUND: Breast augmentation is one of the most commonly performed operations.
      Three-dimensional outcome simulation can be used to predict and demonstrate for
      the patient what the planned operation aims to achieve in terms of size and
      shape. However, there are still few studies in the literature that look at how
      close the simulation is to the actual postoperative result and how patients
      perceive the accuracy and usefulness of the simulation. METHODS: A prospective
      series of 150 patients underwent breast augmentation following consultation with
      the aid of three-dimensional simulation images. These patients were evaluated
      with a questionnaire 6 months postoperatively. A retrospective chart review of 52
      patients whose three-dimensional simulations were compared with the postoperative
      photographs were evaluated and graded by an independent panel of investigators.
      RESULTS: The independent panel graded the overall similarity of the three
      dimensional simulations to the actual breasts with a total average score +/- SD
      of 7.5 +/- 0.80 (range, 4.5 to 8.9) using a visual analogue scale ranging from 1
      to 10. The highest average score was given to projection, breast width, and
      height (7.8); the lowest average score was given to intermammary distance (7.0).
      Eighty-six percent of patients felt the simulated image was very accurate in
      predicting the actual result of their breasts. CONCLUSIONS: Patients prefer a
      center that offers three-dimensional imaging technology; they feel that the
      simulation is very accurate and helps them very much in choosing the implant; if
      they could go back in time, they would choose the same implant again. CLINICAL
      QUESTION/LEVEL OF EVIDENCE: Therapeutic, IV.

PMID- 24076674
TI  - Discussion: Three-dimensional simulated images in breast augmentation surgery: an
      investigation of patients' satisfaction and the correlation between prediction
      and actual outcome.

PMID- 24076675
TI  - Plastic surgery improves long-term weight control after bariatric surgery.
AB  - BACKGROUND: The positive impact of Roux-en-Y gastric bypass on weight,
      comorbidities, and health-related quality of life is well documented. However, 50
      percent of patients regain some of the lost weight after 2 years with Roux-en-Y
      gastric bypass and present a mean weight regain of 10 to 15 percent after several
      years, partially losing the previously obtained benefits. The authors hypothesize
      that body contouring could decrease weight regain, leading to better long-term
      weight control after Roux-en-Y gastric bypass. METHODS: In a matched control
      study, variations in weight for 98 patients with body contouring after Roux-en-Y
      gastric bypass were compared with those of 102 matched control patients with Roux
      en-Y gastric bypass alone. Data were collected prospectively at 1, 3, 6, 9, 12,
      and 18 months after Roux-en-Y gastric bypass and then yearly until 7 years.
      RESULTS: After a massive mean weight loss of 45.2 kg during the first 2 years
      after Roux-en-Y gastric bypass, patients with Roux-en-Y gastric bypass alone
      presented a higher continuous mean weight regain than those with Roux-en-Y
      gastric bypass and body contouring (1.78 kg/year versus 0.51 kg/year of weight
      regain, respectively; p = 0.001). After 7 years, patients with Roux-en-Y gastric
      bypass presented significantly higher mean weight regain than patients with Roux
      en-Y gastric bypass and body contouring (i.e., 10.8 percent versus 3.6 percent
      mean weight gain, respectively; p < 0.001). Netting out mean skin excision weight
      of 2.04 kg by body contouring, the weight regain was 22.9 kg for patients with
      Roux-en-Y gastric bypass alone and only 6.2 kg for those with Roux-en-Y gastric
      bypass and body contouring. CONCLUSIONS: The authors demonstrated that patients
      with body contouring present better long-term weight control after Roux-en-Y
      gastric bypass. Therefore, body contouring must be considered as a reconstructive
      operation in the treatment of morbid obesity. CLINICAL QUESTION/LEVEL OF
      EVIDENCE: Therapeutic, III.

PMID- 24076676
TI  - Lateral access recontouring blepharoplasty for rejuvenation of the lower lids.
AB  - BACKGROUND: Effective lower eyelid blepharoplasty is possible in a virtually
      closed fashion without either an anterior subciliary skin incision or a
      transconjunctival incision, both of which put the patient at risk for lower lid
      retraction. METHODS: Over a 6-year period, the author performed lower lid
      rejuvenation with only a lateral incision in 89 consecutive cases in 86 women and
      three men ranging in age from 42 to 65 years. Patients with lower lid laxity,
      prior surgery, trauma, significant excess skin, or festoons were excluded.
      Grading the aged eyelid in stages 1 to 3, with 3 being advanced, this procedure
      is indicated for stage 1 and 2 patients, characterized by deep nasojugal grooves,
      herniated lower lid compartment fat, mild to moderate rhytides, and increased
      lower lid height. The technique uses a lateral incision with dissection under the
      orbicularis and anterior to the orbital septum with release of the orbitomalar
      ligament. Loupe magnification is used. The nasal orbicularis fibers are released
      and the fat compartments are released and sewn to the midface fat using 6-0
      transcutaneous sutures. An orbicularis muscle lift is performed for support and a
      lateral retinacular suspension is performed if necessary. RESULTS: Follow-up
      ranged from 3 months to 6 years, and there have been no major complications. All
      patients have been satisfied with the results. CONCLUSIONS: Lateral incision-only
      lower lid blepharoplasty allows all necessary structures to be addressed for
      rejuvenation by recontouring in selected patients without anterior or posterior
      incisions into the central part of the lid. CLINICAL QUESTION/LEVEL OF EVIDENCE:
      Therapeutic, IV.

PMID- 24076677
TI  - Discussion: Lateral access recontouring blepharoplasty for rejuvenation of the
      lower lids.

PMID- 24076678
TI  - Discussion: Prevalence of endogenous CD34+ adipose stem cells predicts human fat
      graft retention in a xenograft model.

PMID- 24076679
TI  - Complete horizontal skin cell resurfacing and delayed vertical cell infiltration
      into porcine reconstructive tissue matrix compared to bovine collagen matrix and
      human dermis.
AB  - BACKGROUND: Xenogenous dermal matrices are used for hernia repair and breast
      reconstruction. Full-thickness skin replacement is needed after burn or degloving
      injuries with exposure of tendons or bones. The authors used a human skin organ
      culture model to study whether porcine reconstructive tissue matrix (Strattice)
      is effective as a dermal tissue replacement. METHODS: Skin cells or split
      thickness skin grafts were seeded onto human deepidermized dermis, Strattice, and
      Matriderm. Cellular resurfacing and matrix infiltration were monitored by live
      fluorescence imaging, histology, and electron microscopy. Proliferation,
      apoptosis, cell differentiation, and adhesion were analyzed by
      immunohistochemistry. RESULTS: Epithelial resurfacing and vertical proliferation
      were reduced and delayed with both bioartificial matrices compared with
      deepidermized dermis; however, no differences in apoptosis, cell differentiation,
      or basement membrane formation were found. Vertical penetration was greatest on
      Matriderm, whereas no matrix infiltration was found on Strattice in the first 12
      days. Uncompromised horizontal resurfacing was greatest with Strattice but was
      absent with Matriderm. Strattice showed no stimulatory effect on cellular
      inflammation. CONCLUSIONS: Matrix texture and surface properties governed
      cellular performance on tissues. Although dense dermal compaction delayed
      vertical cellular ingrowth for Strattice, it allowed uncompromised horizontal
      resurfacing. Dense dermal compaction may slow matrix decomposition and result in
      prolonged biomechanical stability of the graft. Reconstructive surgeons should
      choose the adequate matrix substitute depending on biomechanical requirements at
      the recipient site. Strattice may be suitable as a dermal replacement at
      recipient sites with high mechanical load requirements.

PMID- 24076680
TI  - A rat model for long-gap peripheral nerve reconstruction.
AB  - BACKGROUND: The rat model has had limited utility for the study of long nerve
      gaps because of the small size of the animal. The authors sought to develop a
      simple, effective rat model for reconstruction of long nerve gap defects.
      METHODS: Fifteen rats had a sciatic nerve transection followed by reconstruction.
      Positive control rats received a 1-cm isograft. Negative control rats received a
      3.5-cm hollow silicone conduit, and experimental rats received a 4-cm isograft;
      these were implanted in a looped configuration to accommodate the long length.
      Nerves were harvested at 6 weeks (1-cm grafts) and 12 weeks (3.5-cm conduits and
      4-cm grafts) for histologic and histomorphometric evaluation. RESULTS: The 1-cm
      and 4-cm isograft groups showed robust regeneration in the distal nerve segment.
      The 3.5-cm hollow conduits showed absolutely no initiation of nerve regeneration.
      Histomorphometric values were as expected for the specified gap length.
      CONCLUSIONS: This study describes a simple and effective long nerve gap rat model
      for experiments on nerve grafts and nerve conduits. The long nerve graft model
      can be useful for studying techniques such as processed nerve grafts, which are
      currently a topic of frequent investigation. The 3.5-cm hollow conduit "no
      regrowth" long-gap model is ideal for investigating conduit-based tissue
      engineering solutions for long-gap nerve repair. The authors' approach overcomes
      the size limitation of the small animal while exploiting the features that make
      the rat the model of choice for preliminary nerve studies.

PMID- 24076681
TI  - Electrophysiologic evaluation of inferior alveolar nerve regenerated by bifocal
      distraction osteogenesis in dogs.
AB  - BACKGROUND: Bifocal distraction osteogenesis has been shown to be a reliable
      method for reconstructing missing bone segments. However, there are no reports
      regarding inferior alveolar nerve regeneration during bifocal distraction. In the
      present study, the authors evaluated the function of inferior alveolar nerve
      regenerated by bifocal distraction after segmental resection in the mandibles of
      dogs. METHODS: Using a bifocal distraction osteogenesis method, the authors
      produced a 10-mm mandibular defect and distracted the transport disk at a rate of
      1 mm/day. The regenerated inferior alveolar nerve was evaluated by
      electrophysiologic analysis that was performed on all dogs after euthanasia at 3,
      6, and 12 months after the first operation. RESULTS: At 6 and 12 months, stable
      evoked potential measurements were obtained from the nerves throughout the study
      on electrophysiologic analyses. CONCLUSIONS: The authors' results indicate that
      the inferior alveolar nerve regenerated by bifocal distraction osteogenesis
      functioned electrophysiologically at 6 months after the first operation. Although
      our research is still at the stage of animal experiments, future application in
      humans is considered to be possible.

PMID- 24076682
TI  - Critical analysis of causality between negative ulnar variance and Kienbock
      disease.
AB  - BACKGROUND: Negative ulnar variance has been associated with Kienbock disease,
      both supporting a causal link and providing a basis for therapeutic
      recommendations. The aim of this study was to determine whether there is a causal
      relationship between Kienbock disease and negative ulnar variance. METHODS: The
      causal relationship between Kienbock disease and negative ulnar variance was
      assessed using three methodologies: (1) an analysis of the quantitative and
      qualitative distribution of ulnar variance in a case-control study of 81 patients
      with Kienbock disease and a control group of 212 healthy wrists; (2) a systematic
      literature review and meta-analysis of six case-control studies (including the
      case-control study presented in this article) to test for an association between
      Kienbock disease and negative ulnar variance; and (3) a determination of causal
      relationship by using the Bradford Hill criteria. RESULTS: The case-control study
      indicated that when Kienbock disease is associated with negative ulnar variance
      (59 of 81), in 75 percent of the cases negative ulnar variance was equal (29 of
      59) or less (15 of 59) pronounced on the contralateral healthy side. The odds
      ratio generated from the meta-analysis demonstrated a significant association
      between Kienbock disease and negative ulnar variance (OR, 3.58; 95 percent CI,
      1.59 to 8.06; p = 0.002, random effects method). Six of nine Bradford Hill
      criteria do not support a causal relationship. CONCLUSIONS: The significant
      association between Kienbock disease and negative ulnar variance can be well
      explained by selection bias because magnetic resonance imaging, which may detect
      and allow exclusion of a potential ulnar impaction syndrome, was performed in
      only the Kienbock disease group in all six case-control studies. The application
      of the Bradford Hill criteria does not provide sufficient scientific evidence to
      support a causal relationship between Kienbock disease and negative ulnar
      variance. CLINICAL QUESTION/LEVEL OF EVIDENCE: Risk, III.

PMID- 24076683
TI  - Clinical factors associated with replantation after traumatic major upper
      extremity amputation.
AB  - BACKGROUND: Little knowledge exists concerning replantation following traumatic
      major upper extremity amputation. This study characterizes the injury patterns
      and outcomes of patients suffering major upper extremity amputation and
      ascertains clinical factors associated with the decision to attempt replantation.
      METHODS: A retrospective cohort study was conducted on patients treated at a
      Level I trauma center between June of 2000 and August of 2011. Patients who
      experienced traumatic upper extremity amputation at or proximal to the
      radiocarpal joint were included in the study. The subset of patients subsequently
      undergoing replantation was identified. Medical records were reviewed and
      bivariate analysis was performed to identify factors associated with attempted
      replantation and replant survival. RESULTS: Sixty-two patients were treated for
      traumatic upper extremity amputation and 20 patients underwent replantation.
      Injury factors associated with attempted replantation included a
      sharp/penetrating injury (p = 0.004), distal level of amputation (p = 0.017),
      Injury Severity Score less than 16 (p = 0.020), absence of avulsion (p = 0.002),
      absence of significant contamination (p <= 0.001), and lack of multilevel
      involvement (p = 0.007). Replantation exhibited a complete replant survival rate
      of 70 percent. An Injury Severity Score of 16 or more was associated with replant
      failure (p = 0.004). Patients who underwent replantation demonstrated increased
      rates of secondary surgical revisions (p <= 0.001) and complications (p = 0.023)
      and had a greater length of hospital stay (p = 0.024). CONCLUSIONS: Several
      injury characteristics are associated with the decision to attempt replantation
      of the major upper extremity. A high global injury severity (Injury Severity
      Score >= 16) is associated with replantation failure when attempted. Patients who
      undergo replantation demonstrate higher resource use, warranting further cost
      analysis and outcomes investigation. CLINICAL QUESTION/LEVEL OF EVIDENCE: Risk,
      III.

PMID- 24076684
TI  - Secondary cleft nasoplasty at primary school age: quantitative evaluation of the
      efficacy of resorbable plates.
AB  - BACKGROUND: Secondary cleft nasal deformity in children of primary school age can
      result in permanent impact to a child's self-esteem. The ideal technique and
      timing of addressing the deformity remain controversial, as harvest of septal
      cartilage affects nasal growth and limits future options. METHODS: Fifty-three
      patients underwent secondary cleft nasoplasty with resorbable plate placement as
      a columellar strut. All patients had standardized preoperative and postoperative
      photographs. Basilar photographs were analyzed for height and width of each
      nostril, height and width of the nose, and deviation of the nasal tip from
      midline. RESULTS: In unilateral clefts, improvements in nostril width, nostril
      height, tip height, and tip deviation were found to be statistically significant
      in early postoperative photographs; improvements in nostril height, tip height,
      and tip deviation remained statistically significant in late photographs. In
      patients with bilateral clefts, improvements in nostril height and tip height
      were found to be significant in early postoperative photographs, with improvement
      in nostril height remaining significant in the long term. Partial plate exposure
      limited to the columellar base occurred in five patients (9.4 percent),
      successfully treated in the clinic setting with no loss of nasal tip support.
      CONCLUSIONS: The authors provide quantitative data regarding nasal outcomes
      following secondary cleft nasoplasty using resorbable plates for tip support.
      Significant long-term improvements in nasal appearance are possible using this
      technique with minimal complications. In those patients presenting with cleft
      nasal deformity at primary school age, the use of resorbable plates can improve
      nasal symmetry and spare native cartilage and thereby reduce the potential for
      nasal growth disturbance. CLINICAL QUESTION/LEVEL OF EVIDENCE: Therapeutic, IV.

PMID- 24076685
TI  - Soft-tissue profile changes following early Le Fort III distraction in growing
      children with syndromic craniosynostosis.
AB  - BACKGROUND: The purpose of this study was to characterize soft-tissue profile
      changes following Le Fort III (midface) distraction in growing patients with
      syndromic craniosynostosis. METHODS: The cohort consisted of 20 syndromic
      patients who underwent Le Fort III osteotomy with midface advancement using a
      rigid external distraction device. The mean age at surgery was 5.7 years (range,
      3 to 12.5 years). Lateral cephalograms were obtained preoperatively (time 1),
      after distraction device removal (time 2), and 1 year after distraction (time 3).
      Ten skeletal hard-tissue and 11 soft-tissue profile landmarks were identified and
      digitized at time points 1, 2, and 3. The x and y displacement of each landmark
      was studied to determine the ratios for soft- to hard-tissue change. RESULTS: The
      horizontal ratio of soft- to hard-tissue change for nasal dorsum to orbitale was
      0.73:1 and the soft-tissue tip of nose to the anterior nasal spine was 0.86:1.
      The horizontal ratio of soft-tissue A point to hard-tissue A point was 0.88:1.
      The horizontal ratio of the upper lip position to the labial surface of maxillary
      incisor was 0.88:1. The ratio for nasal tip elevation to the anterior nasal spine
      advancement was 0.27:1. CONCLUSIONS: The result of this study supported the
      hypothesis that there exists a linear relationship between soft- and hard-tissue
      changes in the horizontal direction for the midface landmarks following Le Fort
      III distraction. However, there was a nonlinear relationship between soft- and
      hard-tissue changes in the vertical direction. CLINICAL QUESTION/LEVEL OF
      EVIDENCE: Therapeutic, IV.

PMID- 24076686
TI  - Autologous immediate cranioplasty with vascularized bone in high-risk composite
      cranial defects.
AB  - BACKGROUND: Composite cranial defects in the setting of infection, irradiation,
      or cerebrospinal fluid leak present a significant risk for devastating neurologic
      sequelae. Such defects require soft-tissue coverage and skeletal reconstruction
      that can withstand the hostile environment of a precarious wound. METHODS:
      Patients with high-risk composite cranial defects treated with free flap
      reconstruction containing a vascularized osseous component from 2003 to 2012 were
      reviewed retrospectively. RESULTS: Fourteen patients received autologous
      vascularized cranioplasties between 2003 and 2012 with a mean age of 55.7 years
      and a mean follow-up of 14.1 months. Preoperatively, all patients had infection,
      irradiation, cerebrospinal fluid leak, or a combination thereof. Thirteen
      patients (92.9 percent) were reoperative cases for recurrent tumor, infection, or
      both. Six patients (42.9 percent) failed previous reconstructive procedures.
      Tissue biopsy-proven infection was present in 10 patients (71.4 percent) with
      calvarial osteomyelitis, both osteomyelitis and meningitis, or scalp soft-tissue
      infection only. Nine patients (64.3 percent) suffered from malignancy and six of
      these patients were irradiated preoperatively. Cranioplasty was achieved as part
      of a chimeric free flap using rib, scapula, both rib and scapula, or ilium.
      Vascularized duraplasty using serratus anterior fascia as a component of the
      chimeric flap was performed in three patients. No flap losses occurred and all
      patients had resolution of infection. CONCLUSIONS: Soft-tissue and skeletal
      restoration are the two critical components of composite cranial reconstruction.
      The authors report outcomes of the largest series of one-stage immediate
      cranioplasty consisting of autologous soft tissue and vascularized bone in high
      risk composite cranial wounds and suggest its application in defects associated
      with compromised wound beds. CLINICAL QUESTION/LEVEL OF EVIDENCE: Therapeutic,
      IV.

PMID- 24076687
TI  - Development of a reliable model of total abdominal wall transplantation.
AB  - BACKGROUND: Among the most common complications associated with abdominal organ
      transplantation are issues with abdominal wall closure. This difficulty, along
      with the recent rise in the use of vascularized composite allotransplantation,
      has led surgeons to the notion of abdominal wall transplantation. METHODS: The
      authors have developed a novel surgical model for a full-thickness total
      abdominal wall transplant based on a unilateral pedicle between fully major
      histocompatibility complex-mismatched rat strains. An established cuff technique
      was used to anastomose the donor's common iliac vessels to the recipient's
      femoral vessels. Three groups (n = 6 per group) received FK506 monotherapy, 0.25,
      0.50, or 0.75 mg/kg per day. The transplants were assessed daily for evidence of
      rejection by visual inspection. Hematoxylin and eosin skin biopsies and
      fluorescence-activated cell sorting analysis of the recipients' peripheral blood
      were performed. RESULTS: No signs of rejection were observed in the animals
      receiving FK506, 0.50 or 0.75 mg/kg per day. Those receiving 0.25 mg/kg per day,
      however, displayed a mixed rejection response. Flow cytometric analysis did not
      show evidence of donor-specific chimerism. CONCLUSIONS: A full-thickness
      abdominal wall graft based on a unilateral pedicle is a technically feasible and
      reliable small-animal surgical model. The use of greater than or equal to 0.50
      mg/kg per day FK506 results in 100 percent graft survival. Future plans are to
      use this model to investigate the immunologic interaction of a concomitant solid
      organ and an abdominal wall allograft, as would likely occur in the clinical
      situation.

PMID- 24076688
TI  - Discussion: The role of chronic and perioperative glucose management in high-risk
      surgical closures: a case for tighter glycemic control.

PMID- 24076689
TI  - External valvuloplasty for subcutaneous small veins to prevent venous reflux in
      lymphaticovenular anastomosis for lower extremity lymphedema.
AB  - BACKGROUND: Subcutaneous ecchymosis caused by venous reflux is a preventable
      complication following lymphaticovenular anastomosis. The authors developed a
      series of operative procedures to prevent venous reflux. This is probably the
      first report on valvuloplasty for small subcutaneous veins (diameter, <1 mm).
      METHODS: A total of 165 anastomoses in 39 limbs were operated on using this novel
      procedure (study group). Extended vein dissection was performed to ensure
      inclusion of some venous valves. Venous regurgitation was assessed using a
      retrograde milking test. When regurgitation was observed at all peripheral
      branches, external valvuloplasty was performed at the small subcutaneous vein to
      prevent backflow. The rate of venous reflux was compared with 151 anastomoses in
      34 limbs operated on using conventional procedures (control group). Moreover, the
      amount of volume reduction was compared between the patients with and without
      venous reflux. RESULTS: In the study group, the rate of regurgitation was reduced
      (3.0 percent) by extended vein dissection compared with that in the control group
      (9.9 percent), whereas the regurgitation ceased completely following external
      valvuloplasty (0 percent). In addition, postoperative ecchymosis was prevented
      completely in the study group (8.8 percent in the control group). Perioperative
      improvement in the lower extremity lymphedema index was significantly different
      between the patients with and without venous reflux (with venous reflux, 0.0706
      +/- 0.0742; without venous reflux, 0.0904 +/- 0.0614). CONCLUSIONS: The authors'
      results suggest that these operative procedures could be highly effective in
      preventing venous reflux. Moreover, venous reflux, if not corrected, leads to
      worsening of the results. Excellent results were consistently achieved by
      preventing venous reflux. CLINICAL QUESTION/LEVEL OF EVIDENCE: Therapeutic, III.

PMID- 24076690
TI  - Discussion: Nanofat grafting: basic research and clinical applications.

PMID- 24076691
TI  - So have you been to the Holy Land?

PMID- 24076692
TI  - Looking back: the plastic surgery application and interview process.

PMID- 24076695
TI  - Buried flap reconstruction after nipple-sparing mastectomy: advancing toward
      single-stage breast reconstruction.
AB  - BACKGROUND: Recent evolutions of oncologic breast surgery and reconstruction now
      allow surgeons to offer the appropriate patients a single-stage, autologous
      tissue reconstruction with the least donor-site morbidity. The authors present
      their series of buried free flaps in nipple-sparing mastectomies as proof of
      concept, and to explore indications, techniques, and early outcomes from their
      series. METHODS: From 2001 to 2011, a total of 2262 perforator-based free flaps
      for breast reconstruction were reviewed from the authors' prospectively
      maintained database. RESULTS: There were 338 free flaps performed on 215 patients
      following nipple-sparing mastectomy, including 84 patients who underwent breast
      reconstruction with 134 buried free flaps. Ductal carcinoma in situ and BRCA
      positive were the most common diagnoses, in 26 patients (30.9 percent) each. The
      most common flaps used were the deep inferior epigastric perforator (77.6
      percent), transverse upper gracilis (7.5 percent), profunda artery perforator
      (7.5 percent), and superficial inferior epigastric artery flaps (3.7 percent). An
      implantable Cook-Swartz Doppler was used to monitor all buried flaps. Fat
      necrosis requiring excision was present in 5.2 percent of breast reconstructions,
      and there were three flap losses (2.2 percent). Seventy-eight flaps (58.2
      percent) underwent minor revision for improved cosmesis; 56 (41.8 percent) needed
      no further surgery. CONCLUSIONS: Nipple-sparing mastectomy with immediate
      autologous breast reconstruction can successfully and safely be performed in a
      single stage; however, the authors are not yet ready to offer this as their
      standard of care. CLINICAL QUESTION/LEVEL OF EVIDENCE: Therapeutic, IV.

PMID- 24076696
TI  - Magnetic resonance imaging and ultrasound evaluation after breast autologous fat
      grafting combined with platelet-rich plasma.
AB  - BACKGROUND: Breast lipofilling is a fairly simple and safe procedure if it is
      performed by experienced surgeons. METHODS: The authors evaluated the radiologic
      findings from 24 breasts (15 women) subjected to a lipofilling procedure (two
      sessions) for corrective surgery or cosmetic reasons. Mammography, ultrasound,
      and magnetic resonance imaging were performed before the first lipofilling
      session (T0) and 12 months after the last session (T12); ultrasound and magnetic
      resonance imaging were used 3 months after the first session (Ti) and 3 and 6
      months after the last session (T3 and T6). Volumetric evaluations were also made
      through three-dimensional magnetic resonance imaging reconstruction. RESULTS:
      Ultrasound showed oily cysts in 66.67 percent of the breasts at Ti, 70.83 percent
      at T3, 62.5 percent at T6, and 45.83 percent at T12, whereas magnetic resonance
      imaging detected oily cysts in 8.33 percent at Ti and T3 and T6 months and 4.17
      percent at T12. At Ti, T3, and T6, the cytosteatonecrotic areas identified on
      both ultrasound and magnetic resonance imaging were unchanged (8.33 percent),
      whereas at T12 those cytosteatonecrotic areas were increased on ultrasound (12.5
      percent) and even more on the magnetic resonance imaging scans (16.67 percent).
      The average resorption percentage of injected volume was 15.36 percent at T6
      months and 28.23 percent at T12 months. CONCLUSIONS: Postlipofilling breast
      changes can be distinguished from malignant alterations by experienced
      radiologists and need not interfere with early cancer diagnosis if patients are
      checked regularly. Moreover, magnetic resonance imaging is very useful for breast
      volume assessments and for detecting possible changes during longitudinal study.
      CLINICAL QUESTION/LEVEL OF EVIDENCE: Therapeutic, IV.

PMID- 24076697
TI  - Combined epicanthoplasty and blepharoptosis correction in Asian patients.
AB  - BACKGROUND: In ptosis surgery, not addressing the epicanthal fold leaves a
      persistent rounded nasal scleral triangle, which blunts the effect of ptosis
      repair and leads to patient dissatisfaction. To achieve satisfactory results,
      epicanthoplasty is usually performed with ptosis correction. Furthermore,
      surgeons usually choose epicanthoplasty methods based on personal preference, and
      no guideline exists for selecting optimal methods. The aim of this study was to
      demonstrate the usefulness of a concomitant procedure (ptosis correction and
      epicanthoplasty) and to provide recommendations for the selection of
      epicanthoplasty. METHODS: The medical records of 99 patients that underwent
      simultaneous ptosis correction and epicanthoplasty from September of 2003 to
      January of 2011 were reviewed. Differences between preoperative and postoperative
      interepicanthal distances were analyzed by using patient photographs, and
      interepicanthal distance changes were evaluated for each epicanthoplasty.
      RESULTS: Epicanthoplasty was performed in the 99 patients using elliptical
      excision epicanthoplasty in 24 cases, periciliary epicanthoplasty in 12 cases,
      half-Z epicanthoplasty in eight cases, and V-W epicanthoplasty in 55 cases. Some
      changes in interepicanthal distances were observed after epicanthoplasty.
      Interepicanthal distance changes depended on the method used (elliptical excision
      epicanthoplasty, 3.1 mm; half-Z epicanthoplasty, 4 mm; periciliary
      epicanthoplasty, 5.3 mm; and V-W epicanthoplasty, 5.4 mm). The greatest
      differences between preoperative and postoperative interepicanthal distance
      values were found for periciliary and V-W epicanthoplasty, and these differences
      were statistically significant. No revision operations were conducted, and most
      patients were satisfied with results. CONCLUSIONS: In general, concurrent ptosis
      and epicanthus should be corrected to provide optimal cosmetic benefit.
      Periciliary or V-W epicanthoplasty is indicated when epicanthal folds are severe.
      CLINICAL QUESTION/LEVEL OF EVIDENCE: Therapeutic, IV.

PMID- 24076698
TI  - Discussion: Combined epicanthoplasty and blepharoptosis correction in Asian
      patients.

PMID- 24076699
TI  - Macrolane for volume restoration and contouring of the buttocks: magnetic
      resonance imaging study on localization and degradation.
AB  - BACKGROUND: Macrolane is a biocompatible, biodegradable, injectable stabilized
      hyaluronic acid-based gel of nonanimal origin manufactured using the nonanimal
      stabilized hyaluronic acid technology. This was a substudy to evaluate
      localization, displacement, and degradation of the gel when used for volume
      restoration and shaping of the buttocks. METHODS: Subjects aged 20 years or older
      seeking buttock augmentation received a maximum volume of 400 ml per subject. Gel
      localization and degradation up to 24 months after treatment was assessed using
      magnetic resonance imaging. Subjects carried out a self-assessment of aesthetic
      improvement using the Global Esthetic Improvement Scale. Safety assessments
      included adverse event reporting, blood sampling for analysis of systemic
      inflammatory responses, and body temperature. RESULTS: Eight subjects received a
      mean of 163 ml of nonanimal stabilized hyaluronic acid gel per buttock. After 6,
      12, and 24 months, respectively, 56, 36, and 24 percent of gel remained in the
      buttocks, located primarily in the subcutaneous fat. Sixty percent of subjects
      rated their buttocks as improved up to 24 months after treatment. Over the 24
      months, there was no gel displacement outside of the buttocks area, and the
      aesthetic result was not affected by minor gel displacement within the buttocks.
      There were no major inflammatory reactions or significant adverse events.
      CONCLUSIONS: These data demonstrate that nonanimal stabilized hyaluronic acid gel
      degraded as expected in the buttocks, with minimal displacement. The treatment
      was well tolerated, and subjects' and investigators' perceptions of aesthetic
      augmentation of the buttocks remained high, even if only small volumes of the gel
      remained. CLINICAL QUESTION/LEVEL OF EVIDENCE: Therapeutic, IV.

PMID- 24076700
TI  - Urinary excretion of oxidative damage markers in a rat model of vascularized
      composite allotransplantation.
AB  - BACKGROUND: Vascularized composite allotransplantation is an emerging field of
      transplantation that provides a potential treatment for complex tissue defects
      after traumatic loss or tumor resection and for the repair of congenital
      abnormalities. However, vascularized composite allotransplantation recipients
      have suffered from acute and chronic graft rejection that is associated with
      oxidative stress. This study investigated the oxidative damage in a rat
      vascularized composite allotransplantation model by measuring three urinary
      biomarkers, 8-oxo-7,8-dihydroguanine (8-oxoGua), 8-oxo-7,8-dihydro-2'
      deoxyguanosine (8-oxodG), and malondialdehyde. METHODS: Rats received two
      different immunosuppressants, including cyclosporine A and mycophenolate mofetil
      after transplantation, with one group also receiving mesenchymal stem cells
      before transplantation. Urine was collected and analyzed for 8-oxo-7,8
      dihydroguanine, 8-oxo-7,8-dihydro-2'-deoxyguanosine, and malondialdehyde by
      liquid chromatography coupled to tandem mass spectometry methods. RESULTS: Rats
      undergoing vascularized composite allotransplantation had higher urinary levels
      of 8-oxo-7,8-dihydroguanine, 8-oxo-7,8-dihydro-2'-deoxyguanosine, and
      malondialdehyde compared with rats undergoing syngeneic transplantation.
      Cyclosporine A/mycophenolate mofetil following treatment prolonged the allograft
      survival in a dose-dependent manner. Compared with rats undergoing vascularized
      composite allotransplantation with cyclosporine A/mycophenolate mofetil treatment
      alone, rats undergoing mesenchymal stem cell combined treatment showed the
      longest allograft survival, and had approximately 50 percent lower urinary levels
      of malondialdehyde together with approximately 2.7-times higher levels of 8-oxo
      7,8-dihydroguanine. CONCLUSIONS: Mesenchymal stem cell combined treatment
      efficiently managed oxidative stress in rats undergoing vascularized composite
      allotransplantation, and urinary 8-oxo-7,8-dihydroguanine and malondialdehyde
      could be regarded as good responders to the mesenchymal stem cell therapy.

PMID- 24076702
TI  - Decellularized tracheal matrix scaffold for tracheal tissue engineering: in vivo
      host response.
AB  - BACKGROUND: The authors have previously demonstrated promising results with
      tissue engineered trachea in vitro using decellularized matrix scaffolds. The
      present study aims to investigate the applicability of the construct in vivo.
      METHODS: Tracheae harvested from Brown Norway rats (donor) and Lewis rats
      (recipient) were decellularized with repeated detergent-enzymatic treatment
      cycles. Decellularized Brown Norway tracheal matrix scaffolds were seeded with
      Lewis rat stem cell-derived chondrocytes externally and tracheal epithelial cells
      internally to generate a bilaminated tracheal construct. Brown Norway tracheal
      matrix scaffolds (n = 6), Lewis rat scaffolds (n = 6), and the engineered
      constructs (n = 3) were implanted subcutaneously in Lewis rats and observed for 4
      weeks. Fresh Brown Norway (n = 6) and Lewis rat (n = 6) tracheae were implanted
      as controls. Histologic analysis for macrophage, CD8, and CD4 cell infiltration
      was performed. RESULTS: Allogeneic decellularized matrix scaffold showed
      significantly decreased macrophage, CD8+ and CD4+ cell infiltration compared with
      tracheal allografts, and demonstrated similar level of cell infiltration to
      syngeneic decellularized matrix scaffold. No significant differences in
      macrophage infiltration were observed between syngeneic decellularized matrix
      scaffolds and tracheal isografts. The engineered constructs achieved complete
      epithelial cell coverage and preserved lumen patency; however, chondrocytes
      failed to repopulate the cartilaginous matrix with statically seeding stem cell
      on scaffold. CONCLUSIONS: Decellularized tracheal matrix scaffold did not induce
      significant allograft rejection or foreign body reaction in vivo. Although the
      construct supported reepithelialization, stem cell-derived chondrocytes failed to
      engraft in the heterotopic environment and represent a focus of future
      investigations.

PMID- 24076701
TI  - Deferoxamine administration delivers translational optimization of distraction
      osteogenesis in the irradiated mandible.
AB  - BACKGROUND: The authors' laboratory has previously demonstrated that deferoxamine
      promotes angiogenesis and bone repair in the setting of radiation therapy coupled
      with distraction osteogenesis. However, clinically relevant effects of
      deferoxamine administration on union rate and micro-computed tomographic and
      biomechanical parameters are unknown. The authors posit that administration of
      deferoxamine will increase union rate, mineralization, and strength of the
      regenerate in an irradiated distraction osteogenesis model. METHODS: Sprague
      Dawley rats were randomized into three groups: distraction osteogenesis-control,
      distraction osteogenesis-radiation therapy, and distraction osteogenesis
      radiation therapy-deferoxamine. All animals underwent an osteotomy and
      distraction osteogenesis across a 5.1-mm distraction gap. Irradiated animals
      received 35-Gy human-equivalent radiation therapy 2 weeks before surgery, and
      deferoxamine was injected postoperatively in the regenerate site of treatment
      animals. Animals were killed on postoperative day 40, and mandibles were
      harvested to determine rates of bony union and micro-computed tomographic and
      biomechanical parameters. RESULTS: Compared with irradiated mandibles,
      deferoxamine-treated mandibles exhibited a higher union rate (11 percent versus
      92 percent, respectively). Across micro-computed tomographic and biomechanical
      parameters, significant diminutions were observed with administration of
      radiation therapy, whereas deferoxamine therapy resulted in significant
      restoration to levels of controls, with select metrics exhibiting significant
      increases even beyond controls. CONCLUSIONS: The authors' data confirm that
      deferoxamine restores clinically relevant metrics of bony union and micro
      computed tomographic and biomechanical parameters in a model of irradiated
      distraction osteogenesis in the murine mandible. Their findings support a
      potential use for deferoxamine in treatment protocols to allow predictable and
      reliable use of distraction osteogenesis as a viable reconstructive option in
      patients with head and neck cancer.

PMID- 24076703
TI  - Current concepts in the evaluation and treatment of mallet finger injury.
AB  - The mallet finger is a frequently encountered fingertip injury that leads to
      extensor lag of the distal phalanx. Classification systems stratify these
      injuries as ranging from soft-tissue disruption of the extensor mechanism alone
      to those that have articular involvement and volar subluxation. The management of
      mallet finger injuries varies based on injury pattern and surgeon preference.
      These treatment options include splinting regimens, closed reduction and
      percutaneous pinning, and open reduction and internal fixation. Although the
      final goal of treatment is to establish a congruent joint, the efficacy of each
      treatment modality has been shown to vary.

PMID- 24076704
TI  - Human flexor tendon tissue engineering: in vivo effects of stem cell reseeding.
AB  - BACKGROUND: Tissue-engineered human flexor tendons may be an option to aid in
      reconstruction of complex upper extremity injuries with significant tendon loss.
      The authors hypothesize that human adipose-derived stem cells remain viable
      following reseeding on human tendon scaffolds in vivo and aid in graft
      integration. METHODS: Decellularized human flexor tendons harvested from fresh
      frozen cadavers and reseeded with green fluorescent protein-labeled pooled human
      adipose-derived stem cells were examined with bioluminescent imaging and
      immunohistochemistry. Reseeded repaired tendons were compared biomechanically
      with unseeded controls following implantation in athymic rats at 2 and 4 weeks.
      The ratio of collagen I to collagen III at the repair site was examined using
      Sirius red staining. To confirm cell migration, reseeded and unseeded tendons
      were placed either in contact or with a 1-mm gap for 12 days. Green fluorescent
      protein signal was then detected. RESULTS: Following reseeding, viable cells were
      visualized at 12 days in vitro and 4 weeks in vivo. Biomechanical testing
      revealed no significant difference in ultimate load to failure and 2-mm gap
      force. Histologic evaluation showed host cell invasion and proliferation of the
      repair sites. No increase in collagen III was noted in reseeded constructs. Cell
      migration was confirmed from reseeded constructs to unseeded tendon scaffolds
      with tendon contact. CONCLUSIONS: Human adipose-derived stem cells reseeded onto
      decellularized allograft scaffolds are viable over 4 weeks in vivo. The movement
      of host cells into the scaffold and movement of adipose-derived stem cells along
      and into the scaffold suggests biointegration of the allograft.

PMID- 24076705
TI  - Revisiting the scapular flap: applications in extremity coverage for our U.S.
      combat casualties.
AB  - BACKGROUND: Combat injuries commonly result in massive bony and soft-tissue
      destruction within the extremities. These extremity wounds often require large
      free tissue transfers and/or composite flaps for definitive reconstruction. In
      U.S. military war trauma experience, the authors' practice has found the scapular
      flap increasingly useful for reconstruction of complex extremity injuries. The
      purpose of this study is to report the authors' experience using the scapular
      flap in extremity reconstruction and evaluate the indications for use in the
      authors' patient population. METHODS: All consecutive limb salvage cases
      requiring free flaps from 2009 to 2012 at Walter Reed National Military Medical
      Center were reviewed retrospectively. Scapular flap cases were identified. Data
      collected included Injury Severity Score, flap characteristics, and
      complications. RESULTS: Twelve scapular free flaps were performed for extremity
      reconstruction for combat-related trauma, representing 16.2 percent of all
      microsurgical reconstructions during that period. Cases included eight
      traditional scapular flaps, two osteocutaneous scapular flaps, one chimeric
      latissimus/scapular flap, and one chimeric parascapular/scapular/scapula bone
      flap. The complication rate was 17 percent, consisting of one flap hematoma and
      one donor-site dehiscence. Complication rates were similar between scapular
      flaps, other fasciocutaneous flaps, and muscle flaps. CONCLUSIONS: In a decade of
      war trauma, the authors' practice has found the scapular flap useful for
      reconstruction of complex extremity injuries. This flap is uniquely suited to the
      authors' patients, given the severity of their injuries and rehabilitation needs.
      The scapular flap continues to have various indications in injuries seen within
      the authors' military population that may be applicable to the authors' civilian
      patient counterparts. CLINICAL QUESTION/LEVEL OF EVIDENCE: Therapeutic, IV.

PMID- 24076706
TI  - High-pressure injection injuries in the hand: current treatment concepts.
AB  - BACKGROUND: High-pressure injection injury to the hand and upper extremity is a
      rare but very serious clinical entity. The objective of this article was to
      review the current available literature and highlight important topics. METHODS:
      A PubMed literature search was undertaken with the terms "high pressure injection
      injuries," "injection injuries," "finger injection injuries," and other related
      terms. Articles were reviewed with specific attention to clinical presentation,
      treatment, outcome, and prognostic variables. RESULTS: Most of the available
      literature included case studies, case series, retrospective cohorts, and
      literature reviews. The most common presentation of a high-pressure injection
      injury is a puncture wound on the nondominant index finger of a working class man
      in his mid thirties. Important factors at presentation include the time of injury
      and type and pressure of material injected. Initial treatment should include
      tetanus prophylaxis, broad-spectrum antibiotics, and urgent consultation with a
      hand surgeon. Injections with air, gas, or small amounts of veterinary vaccines
      can usually be managed with observation and serial examinations if there is not
      concern for compartment syndrome. Injections with other liquid materials
      typically require emergent surgical debridement, with the best outcomes occurring
      when treated within 6 hours. A wide surgical irrigation and debridement of
      necrotic tissues should be performed under general or regional anesthesia.
      Organic and caustic materials are associated with a higher amputation rate, and
      decreasing the time from injury to surgery improves the prognosis. CONCLUSIONS:
      High-pressure injection injuries to the hand can result in permanent impairment.
      Proper diagnosis and urgent treatment are essential for a good outcome.

PMID- 24076707
TI  - Surgical management of patients with a history of early Le Fort III advancement
      after they have attained skeletal maturity.
AB  - BACKGROUND: The classic Le Fort III procedure was recommended in syndromic
      craniosynostotic children to reduce exorbitism, improve airway function, and
      decrease dysmorphism. This study reports on a cohort of syndromic
      craniosynostosis patients who have undergone early primary subcranial (classic
      Tessier) Le Fort III advancement and who have been followed longitudinally
      through skeletal maturity and beyond. METHODS: In this study, the Le Fort III
      advancements all occurred between the ages of 3 to 5 years, with a mean age of
      4.6 years. Subsequently, these early Le Fort III patients were followed
      throughout development with longitudinal dental, medical, radiographic, and
      photographic evaluations conducted through skeletal maturity and beyond. For
      study inclusion, the patients had to have preoperative medical photographs and
      cephalometric studies at 6 months and 1, 5, and 10 years postoperatively after
      the primary Le Fort III advancement as well as cephalometric documentation 6
      months and 1 year after the secondary midface advancement after skeletal
      maturity. RESULTS: After early or primary Le Fort III advancement, there was no
      evidence of relapse and only minimal anterior or horizontal postoperative growth
      of the midface. However, there was also a return of occlusal disharmony from
      "anticipated" mandibular growth, approaching a maximum at skeletal maturity. The
      dysmorphic concave facial profile and malocclusion, and airway and ocular
      considerations, provided the impetus for secondary midface surgery after skeletal
      maturity was attained. CONCLUSION: The data demonstrate that early Le Fort III
      advancement performed before the age of mixed dentition does not obviate the need
      for a secondary advancement after skeletal maturity is reached. CLINICAL
      QUESTION/LEVEL OF EVIDENCE: Therapeutic, IV.

PMID- 24076708
TI  - Total cranial vault remodeling for isolated sagittal synostosis: part I.
      Postoperative cranial suture patency.
AB  - BACKGROUND: Total vault reconstruction addresses all phenotypic aspects of
      scaphocephaly. The clinical implications of remodeling across open cranial
      sutures, however, remain unclear. The purpose of this study was to assess patency
      of unaffected sutures following total vault remodeling for isolated sagittal
      synostosis. METHODS: The authors reviewed routine postoperative computed
      tomographic scans of patients who underwent total vault remodeling for isolated
      sagittal synostosis between 2004 and 2008. Sutural patency was scored by a single
      reviewer as follows: 0 = closed, 1 = partial, and 2 = open. Individual suture
      scores were tallied for a total sutural patency score. Computed tomographic scans
      were stratified by postoperative time and craniofacial surgeon. RESULTS: Forty
      two patients met the inclusion criteria. Individual sutural closure rates were
      42.6, 38.3, 74.5, and 74.5 percent for right coronal, left coronal, right
      lambdoidal, and left lambdoidal sutures, respectively. Lambdoidal sutures had a
      significantly higher rate of closure than coronal sutures (OR(Closure), 4.3; 95
      percent CI, 2.3 to 8.0; p < 0.001); lambdoidal patency significantly changed over
      time (chi2 = 9.9, p = 0.04). Across craniofacial surgeons, coronal and lambdoidal
      patency were equivalent. The total sutural patency score did not significantly
      correlate with postoperative time, surgical age, preoperative cephalic index, or
      craniofacial surgeon. CONCLUSIONS: Total vault remodeling for isolated sagittal
      synostosis results in a high degree of secondary craniosynostosis. Lambdoidal
      sutures are especially prone to closure, with their patency diminishing over
      time. At this time, radiographic fusion of adjacent sutures following surgery has
      not been related to any difference in head shape. CLINICAL QUESTION/LEVEL OF
      EVIDENCE: Therapeutic, IV.

PMID- 24076709
TI  - Introducing the tibial-dorsalis pedis osteocutaneous shin flap: a new option for
      oromandibular reconstruction.
AB  - BACKGROUND: The authors investigated the possibility of incorporating a well
      vascularized, partial corticotomy of the anterolateral aspect of the tibia "in
      series" with a dorsalis pedis fasciocutaneous free flap for oromandibular
      reconstruction. METHODS: A cadaveric injection study was performed to
      characterize the vascular territory of the anterior tibial artery with regard to
      the surrounding osseous and soft tissue. The two-point breaking strength of the
      tibia (twist) was examined with fracture strain gauge analysis to determine the
      threshold of tibia corticotomy that would lead to a pathologic fracture. Finally,
      the authors performed an in vivo prospective clinical examination of the tibial
      dorsalis pedis osteocutaneous shin flap. RESULTS: The perfusion study revealed
      that the anterior tibial artery provided a rich matrix of musculofascial
      periosteal blood supply to the anterolateral cortex of the tibia that could
      potentially support free osseous tibial transfer. Two-point osteotomy fracture
      strain gauge analysis demonstrated that the threshold of tibia corticotomy that
      would lead to pathologic fracture of the remaining tibia was greater than 30
      percent. The osteocutaneous shin flap was performed in eight patients. The mean
      follow-up was 61 months. There were no cases of flap loss, salivary fistula,
      nonunion, or tibia pathologic fracture. All patients achieved ambulation.
      CONCLUSIONS: The authors introduce the osteocutaneous tibial-dorsalis pedis free
      vascularized flap as a viable option for oromandibular reconstruction. Its most
      notable advantage is the independent mobility of the skin paddle, in combination
      with bone stock that replicates mandibular bone dimensions, facilitating primary
      osseointegration or denture rehabilitation. CLINICAL QUESTION/LEVEL OF EVIDENCE:
      Therapeutic, IV.

PMID- 24076710
TI  - Treatment of keloids and hypertrophic scars with bleomycin and electroporation.
AB  - BACKGROUND: Keloids and hypertrophic scars are the result of abnormal healing
      responses and dermal tissue proliferation; current surgical procedures can give
      rise to exuberant scarring and permanent functional loss or disfigurement.
      Considering the promising results reported when treating keloids and hypertrophic
      scars with intralesional bleomycin injection and the enhanced effect of bleomycin
      when combined with electroporation, the authors hypothesized that
      electrochemotherapy should be used to treat keloids and hypertrophic scars when
      other treatments have failed. METHODS: Twenty patients with keloids or
      hypertrophic scars were treated with one or more sessions of electrochemotherapy
      and followed prospectively. Bleomycin was administered intravenously followed by
      application of electrical pulses to the lesion site. Treatment efficacy was
      determined either by clinical evaluation (e.g., volume, flattening, pliability,
      erythema) or by the patient's self-reported symptomatology (e.g., pruritus,
      pain). RESULTS: Treatment was well tolerated by patients, and no serious adverse
      events were observed. A median reduction of 87 percent (range, 41 to 100 percent)
      was observed in volume size, and 33 lesions (94 percent) showed a volume
      reduction of more than 50 percent. Scar pliability and erythema scores were also
      significantly reduced (p < 0.0001). A reduction in hitching was observed in 89
      percent of patients (p < 0.0001), and a reduction in pain was observed in 94
      percent (p < 0.0001). Only one recurrence was observed after 18 months.
      CONCLUSION: Electroporation in combination with bleomycin is an effective
      treatment for patients affected by large keloids or hypertrophic scars or
      patients who are nonresponders to other treatments. CLINICAL QUESTION/LEVEL OF
      EVIDENCE: Therapeutic, IV.

PMID- 24076711
TI  - Fascia lata allografts as biological mesh in abdominal wall repair: preliminary
      outcomes from a retrospective case series.
AB  - BACKGROUND: The use of biological meshes in management of infected abdominal
      hernias or in abdominal fields at high risk of infection (potentially
      contaminated or with relevant comorbidities) is well established. Available
      products include xenogenic patches or decellularized dermal allografts. Despite
      their biomechanical features, banked fascial allografts have not been
      investigated yet in this setting. The authors evaluated the safety and
      effectiveness of banked fascia lata allografts as biological meshes in abdominal
      wall repair. METHODS: A consecutive series of patients affected by abdominal wall
      defects and who were candidates for repair by means of a biological mesh and
      treated in the authors' institution with banked fascia lata allografts were
      reviewed retrospectively. Data from clinical and instrumental follow-up
      evaluations up to 48 months (average, 23 months) were analyzed. RESULTS: Twenty
      one patients (aged 1 to 86 years) with abdominal wall defects resulting from
      traumatic (n = 1), neoplastic (n = 6), or multiple previous laparotomies (n = 14)
      were treated from January of 2008 to October of 2012. Operations had no relevant
      postoperative complications. At clinical/instrumental follow-up examinations, no
      major signs of recurrence, laxity, infection of grafts, or other related
      pathologic symptoms were recorded. Three patients suffered from temporary minor
      complications (e.g., wound seroma, partial cutaneous dehiscence). At instrumental
      (computed tomographic scan or magnetic resonance imaging) evaluations, the
      neofascial tissue appeared stable until medium-term follow-up (3 to 6 months),
      later being gradually degraded and apparently replaced by host tissue.
      CONCLUSION: According to limited preliminary outcomes, banked fascia lata
      allografts seem to provide a biocompatible, safe, and effective alternative to
      other biological meshes. CLINICAL QUESTION/LEVEL OF EVIDENCE: Therapeutic, IV.

PMID- 24076712
TI  - Discussion: Fascia lata allografts as biological mesh in abdominal wall repair:
      preliminary outcomes from a retrospective case series.

PMID- 24076713
TI  - Mastopexy.
AB  - Mastopexy includes multiple skin incision design and parenchymal manipulation
      options. Patient evaluation includes assessment of goals, degree of ptosis,
      tissue volume, skin quality, and breast position on the chest wall. There are
      critical technical details for each of the three incision options, the various
      methods of parenchymal manipulation, and implant placement. The potential for
      complications is greatest for combined augmentation and mastopexy. Although they
      are effective, mastopexy procedures have the greatest incidence of litigation
      among aesthetic breast procedures.

PMID- 24076714
TI  - Evidence-based Plastic and Reconstructive Surgery: developments over two decades.
AB  - BACKGROUND: Increasing awareness of the importance of evidence-based medicine is
      demonstrated not only by an increasing number of articles addressing it but also
      by a specialty-wide evidence-based medicine initiative. The authors critically
      analyzed the quality of reporting of randomized controlled trials published in
      this Journal over a 21-year period (1990 to 2010). METHODS: A hand search was
      conducted, including all issues of Plastic and Reconstructive Surgery from
      January of 1990 to December of 2010. All randomized controlled trials published
      during this time period were identified with the Cochrane decision tree for
      identification of randomized controlled trials. To assess the quality of
      reporting, a modification of the checklist of the Consolidated Standard of
      Reporting Trials Statement was used. RESULTS: Of 7121 original articles published
      from 1990 to 2010 in the Journal, 159 (2.23 percent) met the Cochrane criteria. A
      significant increase in the absolute number of randomized controlled trials was
      seen over the study period (p < 0.0001). The median quality of these trials from
      1990 to 2010 was "fair," with a trend toward improved quality of reporting over
      time (p = 0.127). CONCLUSIONS: A favorable trend is seen with respect to an
      increased number of published randomized controlled trials in Plastic and
      Reconstructive Surgery. Adherence to standard reporting guidelines is
      recommended, however, to further improve the quality of reporting. Consideration
      may be given to providing information regarding the quality of reporting in
      addition to the "level of evidence pyramid," thus facilitating critical
      appraisal.

PMID- 24076715
TI  - Nasal aesthetics: a cross-cultural analysis.

PMID- 24076716
TI  - Reply: Nasal aesthetics: a cross-cultural analysis.

PMID- 24076717
TI  - Outcomes of surgical excision with pressure therapy using magnets and
      identification of risk factors for recurrent keloids.

PMID- 24076718
TI  - Reply: Outcomes of surgical excision with pressure therapy using magnets and
      identification of risk factors for recurrent keloids.

PMID- 24076719
TI  - The volumetric analysis of fat graft survival in breast reconstruction.

PMID- 24076720
TI  - Reply: The volumetric analysis of fat graft survival in breast reconstruction.

PMID- 24076721
TI  - Nipple sensation losses in Hall-Findlay breast reduction technique.

PMID- 24076722
TI  - Reply: Nipple sensation losses in Hall-Findlay breast reduction techniques.

PMID- 24076723
TI  - A paradigm shift in U.S. breast reconstruction: part 2. The influence of changing
      mastectomy patterns on reconstructive rate and method.

PMID- 24076724
TI  - S-shaped brachioplasty: an effective technique to correct excess skin and fat of
      the upper arm.

PMID- 24076725
TI  - Reply: S-shaped brachioplasty: an effective technique to correct excess skin and
      fat of the upper arm.

PMID- 24076726
TI  - Acellular dermal matrix in hand reconstruction.

PMID- 24076727
TI  - Reply: Acellular dermal matrix in hand reconstruction.

PMID- 24076728
TI  - Arterial and venous revascularization with bifurcation of a single central
      artery: a reliable strategy for Tamai zone I replantation.

PMID- 24076729
TI  - Buttock augmentation with silicone implants: a multicenter survey review of 2226
      patients.

PMID- 24076730
TI  - Reply: Buttock augmentation with silicone implants: a multicenter survey review
      of 2226 patients.

PMID- 24076731
TI  - So you want to become a plastic surgeon? What you need to do and know to get into
      a plastic surgery residency.

PMID- 24076732
TI  - Reply: So you want to become a plastic surgeon? What you need to do and know to
      get into a plastic surgery residency.

PMID- 24076733
TI  - Plastic surgery and smoking: a prospective analysis of incidence, compliance, and
      complications.

PMID- 24076734
TI  - Reply: Plastic surgery and smoking: a prospective analysis of incidence,
      compliance, and complications.

PMID- 24076735
TI  - Alignment of the double-barrel fibula free flap for better cosmesis and bone
      height for osseointegrated dental implants.

PMID- 24076736
TI  - Is there enough evidence to use lipofilling in breast cancer reconstruction?

PMID- 24076737
TI  - The use of human acellular dermal matrix in the first stage of implant-based
      breast reconstruction simplifies the exchange procedure.

PMID- 24076738
TI  - Insurance coverage and reduction mammaplasty: a systematic review of current
      health care policies.

PMID- 24076739
TI  - An easy and novel method of preoperative laser-assisted marking for body lift
      procedures.

PMID- 24076740
TI  - Preexisting deep venous thrombosis in the peroneal vein of a free vascularized
      fibular graft.

PMID- 24076741
TI  - A helping hand for finding the right fellowship match.

PMID- 24076742
TI  - Re: Fernando Ortiz-Monasterio, M.D., 1923 to 2012.

PMID- 24076743
TI  - Unintended consequences? Water molecules at biological and crystallographic
      protein-protein interfaces.
AB  - The importance of protein-protein interactions (PPIs) is becoming increasingly
      appreciated, as these interactions lie at the core of virtually every biological
      process. Small molecule modulators that target PPIs are under exploration as new
      therapies. One of the greatest obstacles faced in crystallographically
      determining the 3D structures of proteins is coaxing the proteins to form
      "artificial" PPIs that lead to uniform crystals suitable for X-ray diffraction.
      This work compares interactions formed naturally, i.e., "biological", with those
      artificially formed under crystallization conditions or "non-biological". In
      particular, a detailed analysis of water molecules at the interfaces of high
      resolution (<=2.30 A) X-ray crystal structures of protein-protein complexes,
      where 140 are biological protein-protein complex structures and 112 include non
      biological protein-protein interfaces, was carried out using modeling tools based
      on the HINT forcefield. Surprisingly few and relatively subtle differences were
      observed between the two types of interfaces: (i) non-biological interfaces are
      more polar than biological interfaces, yet there is better organized hydrogen
      bonding at the latter; (ii) biological associations rely more on water-mediated
      interactions with backbone atoms compared to non-biological associations; (iii)
      aromatic/planar residues play a larger role in biological associations with
      respect to water, and (iv) Lys has a particularly large role at non-biological
      interfaces. A support vector machines (SVMs) classifier using descriptors from
      this study was devised that was able to correctly classify 84% of the two
      interface types.

PMID- 24076744
TI  - Metastastic choriocarcinoma in a term pregnancy: a case study.
AB  - The focus of this article is choriocarcinoma (CC), a rare and aggressive
      obstetric/gynecologic cancer that occurs once in every 20,000 to 40,000
      pregnancies. CC is a form of gestational trophoblastic disease, which is the
      result of abnormal trophoblastic activity encompassing a spectrum of nonmalignant
      and malignant disease. Forms of gestational trophoblastic disease include
      complete or partial mole, invasive mole, CC, placental site trophoblastic tumor,
      and epithelioid trophoblastic tumor. Typically asymptomatic, the first symptom of
      CC in 80% of cases is shortness of breath, indicative of metastasis to the lungs.
      CC affects women of all ages and can occur during pregnancy, after birth, or even
      years remote from the antecedent pregnancy. It is highly responsive to
      chemotherapy, with an overall remission rate greater than 90%. This case study
      presents the story of a pregnant adolescent thought to have an uneventful
      pregnancy until metastatic CC at term was diagnosed. Available treatments,
      outcomes and surveillance for the disease, psychosocial aspects, and implications
      for nursing care are discussed.

PMID- 24076745
TI  - Assessment of life after prematurity in 9- to 10- year-old children.
AB  - PURPOSE: To determine the extent to which alterations in health-related quality
      of life (HRQOL) and special healthcare needs are experienced by children born
      prematurely, compared to those born at term. STUDY DESIGN AND METHODS: A
      descriptive comparative design was utilized. A total of 96 children (preterm N =
      47, term N = 49) completed the PedsQL 4.0 Generic Core Scales 8- to 12-year-old
      self-report version. Parents of both groups of children completed the PedsQL 4.0
      Generic Core Scales parent-proxy version, the Children with Special Health Care
      Needs (CSHCN) Screener, and a demographic data form. RESULTS: Special healthcare
      needs were experienced by more than one half of the premature children evaluated.
      Mean HRQOL scores were significantly different between the children born
      prematurely and their peers born at term. Parents of both groups reported higher
      HRQOL scores than their children self-reported. CLINICAL NURSING IMPLICATIONS:
      Given the sustained high rate of premature birth, understanding of current health
      status of children born prematurely is critical for maternal-child nurses.
      Advocacy and coordination of care are important to improve the healthcare
      provided to families of children born prematurely. Future nursing research should
      incorporate assessment of special healthcare needs and HRQOL of children.

PMID- 24076746
TI  - Structural transitions of epitaxial ceria films on Si(111).
AB  - The structural changes of a (111) oriented CeO2 film grown on a Si(111) substrate
      covered with a hex-Pr2O3(0001) interface layer due to post deposition annealing
      are investigated. X-ray photoelectron spectroscopy measurements revealing the
      near surface stoichiometry show that the film reduces continuously upon extended
      heat treatment. The film is not homogeneously reduced since several coexisting
      crystalline ceria phases are stabilized due to subsequent annealing at different
      temperatures as revealed by high resolution low energy electron diffraction and X
      ray diffraction. The electron diffraction measurements show that after annealing
      at 660  degrees C the iota-phase (Ce7O12) is formed at the surface which exhibits
      a (?7 * ?7)R19.1 degrees  structure. Furthermore, a (?27 * ?27)R30 degrees 
      surface structure with a stoichiometry close to Ce2O3 is stabilized after
      annealing at 860  degrees C which cannot be attributed to any bulk phase of ceria
      stable at room temperature. In addition, it is shown that the fully reduced ceria
      (Ce2O3) film exhibits a bixbyite structure. Polycrystalline silicate
      (CeSi(x)O(y)) and crystalline silicide (CeSi1.67) are formed at 850  degrees C
      and detected at the surface after annealing above 900  degrees C.

PMID- 24076747
TI  - A sea of standards for omics data: sink or swim?
AB  - In the era of Big Data, omic-scale technologies, and increasing calls for data
      sharing, it is generally agreed that the use of community-developed, open data
      standards is critical. Far less agreed upon is exactly which data standards
      should be used, the criteria by which one should choose a standard, or even what
      constitutes a data standard. It is impossible simply to choose a domain and have
      it naturally follow which data standards should be used in all cases. The 'right'
      standards to use is often dependent on the use case scenarios for a given
      project. Potential downstream applications for the data, however, may not always
      be apparent at the time the data are generated. Similarly, technology evolves,
      adding further complexity. Would-be standards adopters must strike a balance
      between planning for the future and minimizing the burden of compliance. Better
      tools and resources are required to help guide this balancing act. 

PMID- 24076748
TI  - Mining high-dimensional administrative claims data to predict early hospital
      readmissions.
AB  - BACKGROUND: Current readmission models use administrative data supplemented with
      clinical information. However, the majority of these result in poor predictive
      performance (area under the curve (AUC)<0.70). OBJECTIVE: To develop an
      administrative claim-based algorithm to predict 30-day readmission using
      standardized billing codes and basic admission characteristics available before
      discharge. MATERIALS AND METHODS: The algorithm works by exploiting high
      dimensional information in administrative claims data and automatically selecting
      empirical risk factors. We applied the algorithm to index admissions in two types
      of hospitalized patient: (1) medical patients and (2) patients with chronic
      pancreatitis (CP). We trained the models on 26,091 medical admissions and 3218 CP
      admissions from The Johns Hopkins Hospital (a tertiary research medical center)
      and tested them on 16,194 medical admissions and 706 CP admissions from Johns
      Hopkins Bayview Medical Center (a hospital that serves a more general patient
      population), and vice versa. Performance metrics included AUC, sensitivity,
      specificity, positive predictive values, negative predictive values, and F
      measure. RESULTS: From a pool of up to 5665 International Classification of
      Diseases, 9th Revision, Clinical Modification (ICD-9-CM) diagnoses, 599 ICD-9-CM
      procedures, and 1815 Current Procedural Terminology codes observed, the algorithm
      learned a model consisting of 18 attributes from the medical patient cohort and
      five attributes from the CP cohort. Within-site and across-site validations had
      an AUC>=0.75 for the medical patient cohort and an AUC>=0.65 for the CP cohort.
      CONCLUSIONS: We have created an algorithm that is widely applicable to various
      patient cohorts and portable across institutions. The algorithm performed
      similarly to state-of-the-art readmission models that require clinical data.

PMID- 24076749
TI  - Sharing behavioral data through a grid infrastructure using data standards.
AB  - OBJECTIVE: In an effort to standardize behavioral measures and their data
      representation, the present study develops a methodology for incorporating
      measures found in the National Cancer Institute's (NCI) grid-enabled measures
      (GEM) portal, a repository for behavioral and social measures, into the cancer
      data standards registry and repository (caDSR). METHODS: The methodology consists
      of four parts for curating GEM measures into the caDSR: (1) develop unified
      modeling language (UML) models for behavioral measures; (2) create common data
      elements (CDE) for UML components; (3) bind CDE with concepts from the NCI
      thesaurus; and (4) register CDE in the caDSR. RESULTS: UML models have been
      developed for four GEM measures, which have been registered in the caDSR as CDE.
      New behavioral concepts related to these measures have been created and
      incorporated into the NCI thesaurus. Best practices for representing measures
      using UML models have been utilized in the practice (eg, caDSR). One dataset
      based on a GEM-curated measure is available for use by other systems and users
      connected to the grid. CONCLUSIONS: Behavioral and population science data can be
      standardized by using and extending current standards. A new branch of CDE for
      behavioral science was developed for the caDSR. It expands the caDSR domain
      coverage beyond the clinical and biological areas. In addition, missing terms and
      concepts specific to the behavioral measures addressed in this paper were added
      to the NCI thesaurus. A methodology was developed and refined for curation of
      behavioral and population science data.

PMID- 24076750
TI  - Supervised embedding of textual predictors with applications in clinical
      diagnostics for pediatric cardiology.
AB  - OBJECTIVE: Electronic health records possess critical predictive information for
      machine-learning-based diagnostic aids. However, many traditional machine
      learning methods fail to simultaneously integrate textual data into the
      prediction process because of its high dimensionality. In this paper, we present
      a supervised method using Laplacian Eigenmaps to enable existing machine learning
      methods to estimate both low-dimensional representations of textual data and
      accurate predictors based on these low-dimensional representations at the same
      time. MATERIALS AND METHODS: We present a supervised Laplacian Eigenmap method to
      enhance predictive models by embedding textual predictors into a low-dimensional
      latent space, which preserves the local similarities among textual data in high
      dimensional space. The proposed implementation performs alternating optimization
      using gradient descent. For the evaluation, we applied our method to over 2000
      patient records from a large single-center pediatric cardiology practice to
      predict if patients were diagnosed with cardiac disease. In our experiments, we
      consider relatively short textual descriptions because of data availability. We
      compared our method with latent semantic indexing, latent Dirichlet allocation,
      and local Fisher discriminant analysis. The results were assessed using four
      metrics: the area under the receiver operating characteristic curve (AUC),
      Matthews correlation coefficient (MCC), specificity, and sensitivity. RESULTS AND
      DISCUSSION: The results indicate that supervised Laplacian Eigenmaps was the
      highest performing method in our study, achieving 0.782 and 0.374 for AUC and
      MCC, respectively. Supervised Laplacian Eigenmaps showed an increase of 8.16% in
      AUC and 20.6% in MCC over the baseline that excluded textual data and a 2.69% and
      5.35% increase in AUC and MCC, respectively, over unsupervised Laplacian
      Eigenmaps. CONCLUSIONS: As a solution, we present a supervised Laplacian Eigenmap
      method to embed textual predictors into a low-dimensional Euclidean space. This
      method allows many existing machine learning predictors to effectively and
      efficiently capture the potential of textual predictors, especially those based
      on short texts.

PMID- 24076751
TI  - An informatics approach to medication adherence assessment and improvement using
      clinical, billing, and patient-entered data.
AB  - The aim of this study was to describe an integrated informatics approach to
      aggregating and displaying clinically relevant data that can identify problems
      with medication adherence and facilitate patient-provider communication about
      strategies to improve medication use. We developed a clinical dashboard within an
      electronic health record (EHR) system that uses data from three sources: the
      medical record, pharmacy claims, and a personal health record. The data are
      integrated to inform clinician-patient discussions about medication adherence.
      Whereas prior research on assessing patterns of medication adherence focused on a
      single approach using the EHR, pharmacy data, or patient-entered data, we present
      an approach that integrates multiple electronic data sources increasingly found
      in practice. Medication adherence is a complex challenge that requires patient
      and provider team input, necessitating an integrated approach using advanced EHR,
      clinical decision support, and patient-controlled technologies. Future research
      should focus on integrated strategies to provide patients and providers with the
      right combination of informatics tools to help them adequately address the
      challenge of adherence to complex medication therapies. 

PMID- 24076753
TI  - Visible-light sensitized luminescent europium(III)-beta-diketonate complexes:
      bioprobes for cellular imaging.
AB  - Visible-light sensitized luminescent europium(III) molecular materials are of
      considerable importance because their outstanding photophysical properties make
      them well suited as labels in fluorescence-based bioassays and low-voltage driven
      pure red-emitters in optoelectronic technology. One challenge in this field is
      development of visible-light sensitizing ligands that can form highly emissive
      europium(III) complexes with sufficient stability and aqueous solubility for
      practical applications. Indeed, some of the recent reports have demonstrated that
      the excitation-window can be shifted to longer-wavelengths in europium(III)-beta
      diketonate complexes by appropriate molecular engineering and suitably expanded
      pi-conjugation in the complex molecules. In this review, attention is focused on
      the latest innovations in the syntheses and photophysical properties of visible
      light sensitized europium(III)-beta-diketonate complexes and their application as
      bioprobes for cellular imaging. Furthermore, luminescent nanomaterials derived
      from long-wavelength sensitized europium(III)-beta-diketonate complexes and their
      application in life sciences are also highlighted.

PMID- 24076752
TI  - Reducing Sexual Risk Behaviors for HIV/STDs in Women with Alcohol Use Disorders.

PMID- 24076754
TI  - Tuning the Poisson's Ratio of Biomaterials for Investigating Cellular Response.
AB  - Cells sense and respond to mechanical forces, regardless of whether the source is
      from a normal tissue matrix, an adjacent cell or a synthetic substrate. In recent
      years, cell response to surface rigidity has been extensively studied by
      modulating the elastic modulus of poly(ethylene glycol) (PEG)-based hydrogels. In
      the context of biomaterials, Poisson's ratio, another fundamental material
      property parameter has not been explored, primarily because of challenges
      involved in tuning the Poisson's ratio in biological scaffolds. Two-photon
      polymerization is used to fabricate suspended web structures that exhibit
      positive and negative Poisson's ratio (NPR), based on analytical models. NPR webs
      demonstrate biaxial expansion/compression behavior, as one or multiple cells
      apply local forces and move the structures. Unusual cell division on NPR
      structures is also demonstrated. This methodology can be used to tune the
      Poisson's ratio of several photocurable biomaterials and could have potential
      implications in the field of mechanobiology.

PMID- 24076756
TI  - Prognostic factors associated with decreased survival in patients with acinic
      cell carcinoma.
AB  - IMPORTANCE: Acinic cell carcinoma is a rare salivary neoplasm that is generally
      associated with a good prognosis, although a subset of patients develops local
      and distant recurrences. Given the rarity of the disease, factors to identify
      patients at risk for recurrences or decreased survival are not clearly defined.
      OBJECTIVES: To identify clinicopathologic factors associated with adverse
      survival in patients with acinic cell carcinoma and to assess the effect of
      local, regional, and distant recurrences on survival. DESIGN, SETTING, AND
      PARTICIPANTS: Retrospective medical record review in a tertiary care cancer
      center of 155 patients treated for acinic cell carcinoma from January 1990
      through February 2013. MAIN OUTCOMES AND MEASURES: Primary outcomes evaluated
      were overall and disease-free survival. The end points assessed were age at
      diagnosis, sex, size of primary tumor, presence of positive surgical margins,
      postoperative radiation therapy, and development of local, regional, or distant
      recurrences. RESULTS: The median survival was 28.5 years, with 13 patients (8.4%)
      dying of their disease. Women (n = 104) were affected twice as often as men (n =
      51) but had an improved survival (P < .001). Patients diagnosed as having acinic
      cell carcinoma before or at the age of 45 years had an improved survival (P =
      .02) compared with their elder counterparts, a finding that was independent of
      sex. Neoplasms larger than 3 cm at presentation were associated with a decreased
      overall survival compared with smaller lesions (P = .02). The development of
      distant metastases was most associated with death from the disease (odds ratio,
      49.90; 95% CI, 6.49-2246.30; P < .001) compared with local and regional
      recurrences. CONCLUSIONS AND RELEVANCE: Although patients with acinic cell
      carcinoma generally have a favorable prognosis, we have identified several
      factors associated with decreased survival, including male sex, age older than 45
      years, neoplasms larger than 3 cm, and the development of a distant recurrence.
      These results suggest that maximizing local and regional control for this disease
      can offer substantial benefit when no distant disease is detectable.

PMID- 24076760
TI  - Bayesian Hierarchical Poisson Regression Models: An Application to a Driving
      Study with Kinematic Events.
AB  - Although there is evidence that teenagers are at a high risk of crashes in the
      early months after licensure, the driving behavior of these teenagers is not well
      understood. The Naturalistic Teenage Driving Study (NTDS) is the first U.S. study
      to document continuous driving performance of newly-licensed teenagers during
      their first 18 months of licensure. Counts of kinematic events such as the number
      of rapid accelerations are available for each trip, and their incidence rates
      represent different aspects of driving behavior. We propose a hierarchical
      Poisson regression model incorporating over-dispersion, heterogeneity, and serial
      correlation as well as a semiparametric mean structure. Analysis of the NTDS data
      is carried out with a hierarchical Bayesian framework using reversible jump
      Markov chain Monte Carlo algorithms to accommodate the flexible mean structure.
      We show that driving with a passenger and night driving decrease kinematic
      events, while having risky friends increases these events. Further the within
      subject variation in these events is comparable to the between-subject variation.
      This methodology will be useful for other intensively collected longitudinal
      count data, where event rates are low and interest focuses on estimating the mean
      and variance structure of the process. This article has online supplementary
      materials.

PMID- 24076757
TI  - Air pollution exposure and lung function in children: the ESCAPE project.
AB  - BACKGROUND: There is evidence for adverse effects of outdoor air pollution on
      lung function of children. Quantitative summaries of the effects of air pollution
      on lung function, however, are lacking due to large differences among studies.
      OBJECTIVES: We aimed to study the association between residential exposure to air
      pollution and lung function in five European birth cohorts with a standardized
      exposure assessment following a common protocol. METHODS: As part of the European
      Study of Cohorts for Air Pollution Effects (ESCAPE) we analyzed data from birth
      cohort studies situated in Germany, Sweden, the Netherlands, and the United
      Kingdom that measured lung function at 6-8 years of age (n = 5,921). Annual
      average exposure to air pollution [nitrogen oxides (NO2, NOx), mass
      concentrations of particulate matter with diameters < 2.5, < 10, and 2.5-10 MUm
      (PM2.5, PM10, and PMcoarse), and PM2.5 absorbance] at the birth address and
      current address was estimated by land-use regression models. Associations of lung
      function with estimated air pollution levels and traffic indicators were
      estimated for each cohort using linear regression analysis, and then combined by
      random effects meta-analysis. RESULTS: Estimated levels of NO2, NOx, PM2.5
      absorbance, and PM2.5 at the current address, but not at the birth address, were
      associated with small decreases in lung function. For example, changes in forced
      expiratory volume in 1 sec (FEV1) ranged from -0.86% (95% CI: -1.48, -0.24%) for
      a 20-MUg/m3 increase in NOx to -1.77% (95% CI: -3.34, -0.18%) for a 5-MUg/m3
      increase in PM2.5. CONCLUSIONS: Exposure to air pollution may result in reduced
      lung function in schoolchildren.

PMID- 24076761
TI  - eXtasy: variant prioritization by genomic data fusion.
AB  - Massively parallel sequencing greatly facilitates the discovery of novel disease
      genes causing Mendelian and oligogenic disorders. However, many mutations are
      present in any individual genome, and identifying which ones are disease causing
      remains a largely open problem. We introduce eXtasy, an approach to prioritize
      nonsynonymous single-nucleotide variants (nSNVs) that substantially improves
      prediction of disease-causing variants in exome sequencing data by integrating
      variant impact prediction, haploinsufficiency prediction and phenotype-specific
      gene prioritization. 

PMID- 24076762
TI  - Orthogonal Cas9 proteins for RNA-guided gene regulation and editing.
AB  - The Cas9 protein from the Streptococcus pyogenes CRISPR-Cas acquired immune
      system has been adapted for both RNA-guided genome editing and gene regulation in
      a variety of organisms, but it can mediate only a single activity at a time
      within any given cell. Here we characterize a set of fully orthogonal Cas9
      proteins and demonstrate their ability to mediate simultaneous and independently
      targeted gene regulation and editing in bacteria and in human cells. We find that
      Cas9 orthologs display consistent patterns in their recognition of target
      sequences, and we identify an unexpectedly versatile Cas9 protein from Neisseria
      meningitidis. We provide a basal set of orthogonal RNA-guided proteins for
      controlling biological systems and establish a general methodology for
      characterizing additional proteins. 

PMID- 24076763
TI  - Improved low-resolution crystallographic refinement with Phenix and Rosetta.
AB  - Refinement of macromolecular structures against low-resolution crystallographic
      data is limited by the ability of current methods to converge on a structure with
      realistic geometry. We developed a low-resolution crystallographic refinement
      method that combines the Rosetta sampling methodology and energy function with
      reciprocal-space X-ray refinement in Phenix. On a set of difficult low-resolution
      cases, the method yielded improved model geometry and lower free R factors than
      alternate refinement methods. 

PMID- 24076764
TI  - Differential abundance analysis for microbial marker-gene surveys.
AB  - We introduce a methodology to assess differential abundance in sparse high
      throughput microbial marker-gene survey data. Our approach, implemented in the
      metagenomeSeq Bioconductor package, relies on a novel normalization technique and
      a statistical model that accounts for undersampling-a common feature of large
      scale marker-gene studies. Using simulated data and several published microbiota
      data sets, we show that metagenomeSeq outperforms the tools currently used in
      this field. 

PMID- 24076765
TI  - Immunogenicity and safety of two doses of a non-adjuvanted influenza A H1N1/2009
      vaccine in young autoimmune rheumatic diseases patients.
AB  - OBJECTIVES: The aim of this study was to evaluate the immunogenicity and safety
      of the influenza A H1N1/2009 vaccine in children under 9 years old with
      autoimmune rheumatic diseases (ARD). METHODS: Thirty-eight ARD patients and 11
      healthy children received two doses of non-adjuvanted influenza
      A/California/7/2009 (H1N1) virus-like vaccine. Subjects were evaluated before and
      21 days after vaccination. Seroprotection (SP) and seroconversion (SC) rates,
      geometric mean titers (GMT) and factor increases (FI) in GMT were calculated.
      RESULTS: Mean ages were comparable between patients and controls. Pre-vaccination
      SP and GMT were similar in patients and controls (p > 0.05). Three weeks after
      immunization, SP (81.6% vs. 81.8%, p = 1.0), SC (81.6% vs. 90.9%, p = 0.66), GMT
      (151.5 vs. 282.1, p = 0.26) and the FI in GMT (16.7 vs. 36.3, p = 0.23) were
      similar in patients and controls, with both groups achieving an adequate
      response, according to the European Medicines Agency and Food and Drug
      Administration standards. Analysis of the possible factors influencing SC showed
      no difference in demographic data, leukocyte/lymphocyte counts or
      immunosuppressant use between seroconverted and non-seroconverted patients (p >
      0.05). The vaccine demonstrated a satisfactory safety profile in this population.
      CONCLUSIONS: Two doses of influenza A H1N1/2009 vaccination induced an effective
      antibody response and caused adverse events in rare instances, suggesting this
      vaccine is appropriate and can be recommended for this age group.

PMID- 24076766
TI  - Modeling the BOLD correlates of competitive neural dynamics.
AB  - Winner-take-all models are commonly used to model decision-making tasks where one
      outcome must be selected from several competing options. Related random walk and
      diffusion models have been used to explain such processes and apply them to
      psychometric and neurophysiological data. Recent model-based fMRI studies have
      sought to find the neural correlates of decision-making processes. However, due
      to the fact that hemodynamic responses likely reflect synaptic rather than
      spiking activity, the expected BOLD signature of winner-take-all circuits is not
      clear. A powerful way to integrate data from neurophysiology and brain imaging is
      by developing biologically plausible neural network models constrained and
      testable by neural and behavioral data, and then using Synthetic Brain Imaging -
      transforming the output of simulations with the model to make predictions
      testable against neuroimaging data. We developed a biologically realistic spiking
      winner-take-all model comprised of coupled excitatory and inhibitory neural
      populations. We varied the difficulty of a decision-making task by adjusting the
      contrast, or relative strength of inputs representing two response options.
      Synthetic brain imaging was used to estimate the BOLD response of the model and
      analyze its peak as a function of input contrast. We performed a parameter space
      analysis to determine values for which the model performs the task accurately,
      and given accurate performance, the distribution of the input contrast-BOLD
      response relationship. This underscores the need for models grounded in
      neurophysiological data for brain imaging analyses which attempt to localize the
      neural correlates of cognitive processes based on predicted BOLD responses. 

PMID- 24076767
TI  - Had enough of that crummy stuff.

PMID- 24076768
TI  - Penguin tissue as a proxy for relative krill abundance in East Antarctica during
      the Holocene.
AB  - Antarctic krill (Euphausia superba) is a key component of the Southern Ocean food
      web. It supports a large number of upper trophic-level predators, and is also a
      major fishery resource. Understanding changes in krill abundance has long been a
      priority for research and conservation in the Southern Ocean. In this study, we
      performed stable isotope analyses on ancient Adelie penguin tissues and inferred
      relative krill abundance during the Holocene epoch from paleodiets of Adelie
      penguin (Pygoscelis adeliae), using inverse of delta15N (ratio of 15N/14N) value
      as a proxy. We find that variations in krill abundance during the Holocene are in
      accord with episodes of regional climate changes, showing greater krill abundance
      in cold periods. Moreover, the low delta15N values found in modern Adelie
      penguins indicate relatively high krill availability, which supports the
      hypothesis of krill surplus in modern ages due to recent hunt for krill-eating
      seals and whales by humans.

PMID- 24076769
TI  - Proton computed tomography from multiple physics processes.
AB  - Proton CT (pCT) nowadays aims at improving hadron therapy treatment planning by
      mapping the relative stopping power (RSP) of materials with respect to water. The
      RSP depends mainly on the electron density of the materials. The main information
      used is the energy of the protons. However, during a pCT acquisition, the spatial
      and angular deviation of each particle is recorded and the information about its
      transmission is implicitly available. The potential use of those observables in
      order to get information about the materials is being investigated. Monte Carlo
      simulations of protons sent into homogeneous materials were performed, and the
      influence of the chemical composition on the outputs was studied. A pCT
      acquisition of a head phantom scan was simulated. Brain lesions with the same
      electron density but different concentrations of oxygen were used to evaluate the
      different observables. Tomographic images from the different physics processes
      were reconstructed using a filtered back-projection algorithm. Preliminary
      results indicate that information is present in the reconstructed images of
      transmission and angular deviation that may help differentiate tissues. However,
      the statistical uncertainty on these observables generates further challenge in
      order to obtain an optimal reconstruction and extract the most pertinent
      information. 

PMID- 24076770
TI  - The occasional role of low-risk human papillomaviruses 6, 11, 42, 44, and 70 in
      anogenital carcinoma defined by laser capture microdissection/PCR methodology:
      results from a global study.
AB  - Low-risk human papillomaviruses (LR-HPVs) have been associated occasionally with
      clinically and pathologically unusual anogenital malignancies. The relation
      between clinicopathologic features and any pathogenetic role of LR-HPV remains
      unclear. From a global study of 13,328 anogenital carcinomas, we identified 57
      cases in which whole-tissue polymerase chain reaction using SPF10-LiPA25 showed
      single LR-HPV infection. In 43/46 (93.5%) available carcinomas, multiple
      polymerase chain reaction assays confirmed single detection of HPV6, 11, 42, 44,
      or 70 DNA. In 75% (n=32) of these, LR-HPV DNA was confirmed in tumor cells by
      laser capture microdissection. In 2 cases, including 1 adenocarcinoma, viral DNA
      was only found outside the tumor. All anogenital tumors with confirmed HPV6/11
      showed a distinctive range of papillary, warty or warty-basaloid, squamous, or
      transitional histology with patchy or negative p16 expression. HPV6-associated
      cervical tumors occurred at a low median age. HPV42/70 was associated with
      typical squamous cell carcinoma showing diffuse p16 staining like high-risk HPV
      related malignancies. HPV44 was found in malignant cells in 1 case. Viral
      taxonomy and theoretical analysis show that HPV6/11 belong to a different genus
      from HPV42/70 with E6/E7 gene products that would not bind pRb or p53, whereas
      HPV42/70 could bind pRb. Our data support the causal involvement of LR-HPVs in
      the carcinogenesis of <2% of anogenital malignancies of 2 distinct
      clinicopathologic patterns related to the genetic structure of the HPV types 6/11
      and 70/42. HPV42/70 was associated with typical squamous carcinomas. Importantly
      all carcinomas associated with HPV6/11 globally showed verruco-papillary, well
      differentiated, squamous, or transitional histology without p16 expression. 

PMID- 24076771
TI  - Cervical squamocolumnar junction-specific markers define distinct, clinically
      relevant subsets of low-grade squamous intraepithelial lesions.
AB  - Low-grade cervical squamous abnormalities (low-grade squamous intraepithelial
      lesions [LSIL, CIN1]) can be confused with or followed by high-grade (HSIL,
      CIN2/3) lesions, expending considerable resources. Recently, a cell of origin for
      cervical neoplasia was proposed in the squamocolumnar junction (SCJ); HSILs are
      almost always SCJ, but LSILs include SCJ and SCJ subsets. Abnormal cervical
      biopsies from 214 patients were classified by 2 experienced pathologists (panel)
      as LSIL or HSIL using published criteria. SILs were scored SCJ and SCJ using SCJ
      specific antibodies (keratin7, AGR2, MMP7, and GDA). Assessments of interobserver
      agreement, p16 staining pattern, proliferative index, and outcome were compared.
      The original diagnostician agreed with the panel diagnosis of HSIL and SCJ LSIL
      in all cases (100%). However, for SCJ LSIL, panelists disagreed with each other
      by 15% and with the original diagnostician by 46.2%. Comparing SCJ and SCJ LSILs,
      60.2% and 94.9% were p16 positive, 23% and 74.4% showed strong (full-thickness)
      p16 staining, and 0/54 (0%) and 8/33 (24.2%) with follow-up had an HSIL outcome,
      respectively. Some SCJ LSILs are more likely to both generate diagnostic
      disagreement and be associated with HSIL. Conversely, SCJ LSILs generate little
      observer disagreement and, when followed, have a very low risk of HSIL outcome.
      Thus, SCJ biomarkers in conjunction with histology may segregate LSILs with very
      low risk of HSIL outcome and conceivably could be used as a management tool to
      reduce excess allocation of resources to the follow-up of these lesions. 

PMID- 24076772
TI  - Histologic features in colon biopsies can discriminate mycophenolate from GVHD
      induced colitis.
AB  - Mycophenolate mofetil (MMF) is a T-cell inhibitor frequently used in the
      treatment of acute allograft rejection. MMF may cause colitis that clinically and
      histologically resembles graft-versus-host disease (GVHD). The aim of this study
      was to evaluate a wide range of histologic features that may help differentiate
      MMF from GVHD-induced colitis and to validate significant features on a cohort of
      bone marrow transplant patients who were also taking MMF as part of their
      immunosuppressive regimen and developed a diarrheal illness due to colitis.
      Routinely processed colonic biopsies from 17 patients with MMF colitis and 40
      patients with GVHD-induced colitis were evaluated for the overall grade of
      colitis (grades 1 to 4) and histologically for a wide range of inflammatory,
      epithelial, and architectural changes in a blinded manner. Statistically
      significant features were then tested in a cohort of 20 bone marrow transplant
      patients who also received MMF, and later developed a diarrheal illness. Both
      univariate and multivariate analyses (including receiver operating characteristic
      analysis) were performed. Morphologic features shown to be independently
      associated with MMF include the presence and quantity of lamina propria
      eosinophils and endocrine cell aggregates and the presence and quantity of
      apoptotic microabscesses, hypereosinophilic (degenerated) crypts, and crypt
      distortion. Eosinophils were present in all MMF patients, but apoptotic
      microabscesses were present in none and endocrine cell aggregates in only 1 case.
      When a grade-by-grade comparison was made between MMF and GVHD, grade 1 or 2 MMF
      also showed an increased prevalence rate and quantity of lamina propria
      neutrophils in comparison with grade 1 or 2 GVHD. By receiver operating
      characteristic analysis, a combination of lamina propria eosinophils >15 per 10
      HPF, combined with a lack of endocrine cell aggregates and apoptotic
      microabscesses, revealed sensitivity, specificity, and positive and negative
      predictive values of 76%, 93%, 81%, and 90%, respectively, for identification of
      MMF colitis. On the basis of these data, we conclude that a variety of histologic
      features, in particular, eosinophils >15 per 10 HPF, lack of endocrine cell
      aggregates in the lamina propria, and lack of apoptotic microabscesses, can be
      used by pathologists to help separate MMF from GVHD-induced colitis in routine
      clinical practice. 

PMID- 24076773
TI  - Acinar cell cystadenoma of the pancreas: a benign neoplasm or non-neoplastic
      ballooning of acinar and ductal epithelium?
AB  - Acinar cell cystadenoma (ACA) of the pancreas was initially described as a non
      neoplastic cyst of the pancreas and, at that time, referred to as "acinar cystic
      transformation." In subsequent studies, these lesions were given the designation
      of "-oma," despite the relative lack of evidence supporting a neoplastic process.
      To characterize these lesions further, we examined the clinical, pathologic, and
      immunohistochemical features of 8 ACAs. The majority of patients were female (7
      of 8, 88%) and ranged in age from 18 to 57 years (mean, 43 y). Grossly, the cysts
      involved the head (n=5), body (n=1), or the entire pancreas (n=2). ACAs were
      either multilocular (n=4) or unilocular (n=4) and ranged in size from 1.8 to 15
      cm (mean, 6.8 cm). Histologically, multilocular ACAs were lined by patches of
      acinar and ductal epithelium. Immunolabeling, including double-labeling for
      cytokeratin 19 and chymotrypsin, highlighted the patchy pattern of the ductal and
      acinar cells lining the cysts. In some areas, the cysts with patches of acinar
      and ductal differentiation formed larger locules with incomplete septa as they
      appeared to fuse with other cysts. In contrast, the unilocular cases were lined
      by 1 to 2 cell layers of acinar cells with little intervening ductal epithelium.
      Nuclear atypia, mitotic figures, necrosis, infiltrative growth, and associated
      invasive carcinoma were absent in all cases. In addition, we assessed the clonal
      versus polyclonal nature of ACAs, occurring in women, using X-chromosome
      inactivation analysis of the human androgen receptor (AR) gene. Five of 7 cases
      were informative and demonstrated a random X-chromosome inactivation pattern.
      Clinical follow-up information was available for all patients, and follow-up
      ranged from 10 months to 7.8 years (mean, 3.6 y), with no evidence of recurrence
      or malignant transformation. We hypothesize that early lesions are marked by
      acinar dilatation that expands into and incorporates smaller ductules and later
      larger ducts. As the cysts increase in size, they fuse forming larger cysts.
      Later lesions demonstrate a unilocular cyst lined by predominantly acinar
      epithelium with scattered ductal cells. The term cystadenoma, with its neoplastic
      connotation, does not seem to accurately reflect the histologic,
      immunohistochemical, or molecular features of these lesions. We suggest
      readopting the term "acinar cystic transformation" until the non-neoplastic
      versus neoplastic origin of these lesions can be resolved.

PMID- 24076774
TI  - Interobserver agreement for assessing invasion in stage 1A vulvar squamous cell
      carcinoma.
AB  - Invasive squamous cell carcinoma of the vulva with <=1 mm stromal invasion is
      classified as stage 1A. Cancer staging systems state that the depth of invasion
      should be measured from the epithelial-stromal junction of the adjacent most
      superficial dermal papilla to the deepest point of the invasive tumor.
      Measurement of the depth of invasion guides patient management. Even though this
      measurement is critical, no studies have reported the reliability among
      pathologists for determining the cutoff point of <=1 mm stromal invasion in
      vulvar cancer. We assessed agreement among pathologists for determining whether a
      vulvar tumor is invasive, for the depth of invasion, and for tumor thickness.
      Forty-five cases of vulvar squamous cell carcinoma with a depth of invasion of
      <=5 mm were chosen. Eleven gynecologic pathologists independently reviewed the
      slides and, for a subset of cases, pictorially recorded measurements on
      photographs. The number of cases that were reported as invasive by the 11
      pathologists ranged from 21 to 44. The number of cases that were reported as
      showing a depth of invasion of <=1 mm ranged from 7 to 27. Eight pathologists
      provided measurements for all lesions reported as invasive, the remaining 3
      pathologists stated that they were unable to measure 2, 7, and 16 lesions,
      respectively. Mean kappa for diagnosing vulvar carcinoma as invasive was 0.24 and
      for measuring the depth of invasion and thickness was 0.51 and 0.49,
      respectively. There was only fair agreement in determining whether the lesion was
      invasive. In cases in which pathologists agreed upon the diagnosis of invasion,
      agreement on depth was moderate. When using the recommended cancer staging
      method, interpretation of the location of the most superficial dermal papilla
      varied among pathologists. Measuring thickness did not improve agreement. This is
      the first study that has assessed the reliability of the diagnosis of invasion in
      vulvar cancer among gynecologic pathologists, the interobserver agreement for
      reporting the critical 1 mm threshold of depth of stromal invasion, and the way
      in which the International Federation of Gynecology and Obstetrics method is used
      by pathologists. 

PMID- 24076775
TI  - Loss of ARID1A expression correlates with stages of tumor progression in uterine
      endometrioid carcinoma.
AB  - ARID1A is a recently identified tumor suppressor that functions in chromatin
      remodeling. Inactivating mutations of ARID1A and loss of its expression most
      frequently occur in ovarian clear cell carcinoma, ovarian endometrioid carcinoma,
      and uterine endometrioid carcinoma. In this study, we performed a detailed
      immunostaining analysis of ARID1A in 246 cases including benign endometrium and
      endometrioid carcinoma at different stages of progression. Special attention was
      paid to recording intratumoral heterogeneity of clonal loss of ARID1A
      immunoreactivity. All normal endometria (n=51) and endometrial polyps (n=14)
      retained ARID1A expression. Among complex atypical hyperplasias (n=38), 16%
      exhibited clonal loss of ARID1A, but none showed complete loss. Among low-grade
      endometrioid carcinomas (n=88), 25% exhibited complete loss and 24% exhibited
      clonal loss. In contrast, 44% of high-grade endometrioid carcinomas (n=55) showed
      complete loss of ARID1A, and 9% exhibited clonal loss. We found that 19 high
      grade carcinomas also contained concurrent low-grade carcinomas. In the high
      grade areas, 63% exhibited complete loss and 11% exhibited clonal loss, whereas
      in the low-grade areas, 37% exhibited complete loss and 42% clonal loss. In 5 of
      these 19 cases, progressive loss of ARID1A from retention or clonal loss to
      complete loss was observed between the low-grade and high-grade areas. Overall,
      the percentage of complete ARID1A loss increased from 0% in complex atypical
      hyperplasia, to 25% in low-grade endometrioid carcinoma, to 44% in high-grade
      endometrioid carcinoma. These findings suggest that loss of ARID1A expression,
      presumably due to mutation, plays an important role in tumor progression of
      uterine endometrioid carcinoma. 

PMID- 24076776
TI  - Morphologic characteristics and immunohistochemical profile of diffuse intrinsic
      pontine gliomas.
AB  - Tumors of the central nervous system are the second most common malignancy in
      children. In particular, diffuse intrinsic pontine gliomas (DIPGs) are aggressive
      tumors with poor prognosis and account for 10% to 25% of pediatric brain tumors.
      The majority of DIPGs are astrocytic, infiltrative, and localized to the pons.
      Studies have shown median survival times of less than a year, with 90% of
      children dying within 2 years. We built multitissue arrays with 24 postmortem
      DIPG samples and analyzed the morphology and expression of several proteins (p53,
      EGFR, GFAP, MIB1, BMI1, beta-catenin, p16, Nanog, Nestin, OCT4, OLIG2, SOX2) with
      the goal of identifying potential treatment targets and improving our
      understanding of the biology of these tumors. The majority of DIPGs were high
      grade gliomas (22), with 18 cases having features of glioblastoma (World Health
      Organization [WHO] grade IV) and 4 cases with high-grade features consistent with
      anaplastic astrocytoma (WHO grade III). One case was low grade (WHO grade II),
      and 1 case showed intermediate features between a grade II and grade III glioma
      (low mitotic rate but increased cellularity and cell atypia), being difficult to
      grade precisely. The majority of the tumors were positive for GFAP (24/24), MIB1
      (23/24), OLIG2 (22/24), p16 (20/24), p53 (20/24), SOX2 (19/24), EGFR (16/24), and
      BMI1 (9/24). Our results suggest that dysregulation of EGFR and p53 may play an
      important role in the development of DIPGs. The majority of DIPGs express stem
      cell markers such as SOX2 and OLIG2, consistent with a role for tumor stem cells
      in the origin and maintenance of these tumors. Targeted therapies against these
      proteins could be beneficial in treatment. 

PMID- 24076777
TI  - Intravascular adenomyomatosis: expanding the morphologic spectrum of
      intravascular leiomyomatosis.
AB  - Intravascular leiomyomatosis (IVL) is characterized by the presence of smooth
      muscle in venous and lymphatic spaces within the myometrium. Although the
      intravascular component usually consists solely of typical smooth muscle or
      variants of smooth muscle differentiation, we report 5 cases in which the
      intravascular component also included endometrioid glandular and stromal
      elements. We propose the term "intravenous adenomyomatosis" to describe this
      unusual variant of IVL. The mean age of the patients in this series was 50.2
      years, slightly older than that of patients with conventional IVL. In addition to
      intravenous adenomyomatosis, both adenomyosis and leiomyomas were identified in
      all of our cases, supporting the hypothesis that the intravascular smooth muscle
      component in IVL is derived from associated myometrial pathology rather than from
      vessel walls. In our series, intravenous adenomyomatosis had a similar benign
      clinical behavior to most cases of IVL with no metastatic or recurrent disease
      identified at follow-up in 4 cases for which follow-up information was available.
      The main differential diagnoses are adenomyosis with vascular involvement, low
      grade endometrial stromal sarcoma (ESS), including ESS with smooth muscle and
      glandular differentiation, and adenosarcoma with lymphovascular invasion. The
      possibility of intravenous adenomyomatosis should be borne in mind when
      considering these diagnoses, particularly ESS and adenosarcoma, which have
      different implications for patient management and prognosis. 

PMID- 24076779
TI  - ITK/SYK translocation in angioimmunoblastic T-cell lymphoma.

PMID- 24076778
TI  - Histotype-genotype correlation in 36 high-grade endometrial carcinomas.
AB  - Endometrioid, serous, and clear cell carcinomas are the major types of
      endometrial carcinoma. Histologic distinction between these different tumor types
      can be difficult in high-grade cases, in which significant interobserver
      diagnostic disagreement exists. Endometrioid and clear cell carcinomas frequently
      harbor ARID1A and/or PTEN mutations. Serous carcinoma acquires TP53
      mutations/inactivation at onset, with a significant subset harboring an
      additional mutation in PPP2R1A. This study examines the correlation between tumor
      histotype and genotype in 36 previously genotyped high-grade endometrial
      carcinomas. This included 23 endometrioid/clear cell genotype and 13 serous
      genotype tumors. Eight subspecialty pathologists reviewed representative online
      slides and rendered diagnoses before and after receiving p53, p16, and estrogen
      receptor immunostaining results. kappa statistics for histotype-genotype
      concordance were calculated. The average kappa values for histotype-genotype
      concordance was 0.55 (range, 0.30 to 0.67) on the basis of morphologic evaluation
      alone and it improved to 0.68 (range, 0.54 to 0.81) after immunophenotype
      consideration (P<0.001). Genotype-incompatible diagnoses were rendered by at
      least 2 pathologists in 12 of 36 cases (33%) (3 cases by 2/8 pathologists, 2 by
      3/8, 2 by 4/8, 3 by 6/8, 1 by 7/8, and 1 case by 8/8 pathologists). Six of the 12
      were endometrioid/clear cell genotype tumors, and the other 6 were serous
      genotype tumors. The histopathologic features associated with histotype-genotype
      discordant cases were reviewed, and specific diagnostic recommendations were made
      to improve concordance. This study found that although the majority of
      morphologic diagnoses are genotype concordant, genotype-incompatible diagnoses
      are made in a significant subset of cases. Judicious use and interpretation of
      p53 immunohistochemistry in selected scenarios can improve histotype-genotype
      concordance. 

PMID- 24076780
TI  - Luteinized thecomas (thecomatosis) associated with sclerosing peritonitis exhibit
      positive staining with sex cord markers steroidogenic factor-1 (SF-1) and FOXL2.

PMID- 24076781
TI  - Extracavitary KSHV-positive solid lymphoma: a large B-cell lymphoma within the
      spectrum of primary effusion lymphoma.

PMID- 24076782
TI  - Preparation of three-dimensional braided carbon fiber-reinforced PEEK composites
      for potential load-bearing bone fixations. Part I. Mechanical properties and
      cytocompatibility.
AB  - In this study, we focused on fabrication and characterization of three
      dimensional carbon fiber-reinforced polyetheretherketone (C3-D/PEEK) composites
      for orthopedic applications. We found that pre-heating of 3-D fabrics before hot
      pressing could eliminate pores in the composites prepared by 3-D co-braiding and
      hot-pressing techniques. The manufacturing process and the processing variables
      were studied and optimum parameters were obtained. Moreover, the carbon fibers
      were surface treated by the anodic oxidization and its effect on mechanical
      properties of the composites was determined. Preliminary cell studies with mouse
      osteoblast cells were also performed to examine the cytocompatibility of the
      composites. Feasibility of the C3-D/PEEK composites as load-bearing bone fixation
      materials was evaluated. Results suggest that the C3-D/PEEK composites show good
      promising as load-bearing bone fixations. 

PMID- 24076783
TI  - The effect of collagen-chitosan porous scaffold thickness on dermal regeneration
      in a one-stage grafting procedure.
AB  - Dermal substitutes are used as dermal regeneration templates to reduce scar
      formation and improve wound healing. Unlike autografts, dermal substitutes lack
      normal vascular networks. The increased distance required for diffusion of oxygen
      and nutrients to the autograft following interpositioning of the substitute
      dramatically affects graft survival. To evaluate the effect of collagen-chitosan
      scaffold thickness on dermal regeneration, single-layer collagen-chitosan porous
      scaffolds of 0.5-, 1- and 2-mm thicknesses were fabricated and used to treat full
      thickness wounds in a one-stage grafting procedure in a rat model. Skin-graft
      viability, wound contraction, histological changes, and wound tensile strength
      were evaluated. The results indicated that the distance for the diffusion of
      oxygen and nutrients to the autograft in the 2-mm-thick scaffold provided less
      support for graft take, which resulted in graft necrosis, extensive inflammatory
      reaction, marked foreign-body reaction (FBR), rapid scaffold degradation, and
      abnormal collagen deposition and remodeling. In contrast, the thinner scaffolds,
      especially of that 0.5-mm thickness, promoted earlier angiogenesis, ensuring skin
      graft viability with a mild FBR, and ordered fibroblast infiltration and better
      collagen remodeling. It can be concluded that collagen-chitosan porous scaffolds
      with a thickness of <1mm are more suitable for dermal regeneration and can be
      used as dermal templates for treatment of dermal defects using a one-stage
      grafting procedure. 

PMID- 24076961
TI  - PtII6 nanoscopic cages with an organometallic backbone as sensors for picric
      acid.
AB  - An organometallic building block 1,3,5-tris(4-trans
      Pt(PEt3)2I(ethynyl)phenyl)benzene (1) incorporating Pt-ethynyl functionality has
      been synthesized and characterized. [2 + 3] self-assembly of its nitrate analogue
      1,3,5-tris(4-trans-Pt(PEt3)2(ONO2)(ethynyl)phenyl)benzene (2) with "clip" type
      bidentate donors (L1-L3) separately afforded three trigonal prismatic
      architectures (3a-3c), respectively. All these prisms were characterized and
      their shapes/sizes are predicted through geometry optimization employing
      molecular mechanics universal force field (MMUFF) simulation. The extended pi
      conjugation including the presence of Pt-ethynyl functionality makes them
      electron rich as well as luminescent in nature. Macrocycles 3b and 3c exhibit
      fluorescence quenching in solution upon addition of picric acid [PA], which is a
      common constituent of many explosives. Interestingly, the non-responsive nature
      of fluorescent intensity towards other electron-deficient nitro-aromatic
      explosives (NAEs) makes them promising selective sensors for PA with a detection
      limit predicted to be ppb level. Furthermore, solid-state quenching of
      fluorescent intensity of the thin film of 3b upon exposure to saturated vapor of
      picric acid has drawn special attention for infield applications. 

PMID- 24076962
TI  - Lipopolysaccharide promotes contraction of uterine myocytes via activation of
      Rho/ROCK signaling pathways.
AB  - Myometrial contraction is a central feature of labor. Although a link between
      infection and preterm labor is widely accepted, surprisingly little is known
      about the mechanisms coupling infection-induced inflammation to myocyte
      contractile machinery. This study explores the myocyte response to pathogen
      derived ligands in vitro. The pregnant human myometrial cell line PHM1-41 and
      primary cultured uterine myocytes responded to Toll-like receptor (TLR) ligands,
      including the bacterial wall component LPS, which at 100 ng/ml increased
      contraction of cells embedded within collagen gels over 72 h compared to PBS. LPS
      treated myocytes secreted inflammatory mediators, including prostaglandin
      F2alpha, the cytokines TNF-alpha and IL-6, and a range of chemokines. The
      contractile response to LPS required TLR4 signaling and was independent of
      prostaglandin synthesis. Neutralizing TNF-alpha had no effect on LPS-mediated
      contraction; however, the Rho-associated protein kinase (ROCK) inhibitors Y-27632
      (10 MUM) and GSK-269962 (50 nM) both abrogated the contractile response. The
      finding of LPS-mediated contraction was supported by a 1.38 +/- 0.072-fold
      (mean+/-SE) increase in myosin light-chain phosphorylation 48 h post-treatment,
      assessed by in-cell Western blot analysis. Together, these data suggest that, in
      addition to modulating the local inflammatory environment, pathogen-derived
      ligands may directly promote myometrial contractility via Rho/ROCK signaling,
      thus contributing to preterm labor-mediated preterm birth.

PMID- 24076963
TI  - Sustained nitric oxide (NO)-releasing compound reverses dysregulated NO signal
      transduction in priapism.
AB  - We evaluated the therapeutic potential of a sustained nitric oxide (NO)-releasing
      compound to correct the molecular hallmarks and pathophysiology of priapism, an
      important but poorly characterized erectile disorder. 1,5-Bis-(dihexyl-N
      nitrosoamino)-2,4-dinitrobenzene (C6') and an inactive form of the compound [1,5
      bis-(dihexylamino)-2,4-dinitrobenzene (C6)] were tested in neuronal cell cultures
      and penile lysates for NO release (Griess assay) and biological activity (cGMP
      production). The effect of local depot C6' or C6 was evaluated in mice with a
      priapic phenotype due to double neuronal and endothelial NO synthase deletion
      (dNOS(-/-)) or human sickle hemoglobin transgenic expression (Sickle). Changes in
      NO signaling molecules and reactive oxygen species (ROS) surrogates were assessed
      by Western blot. The physiological response after C6' treatment was assessed
      using an established model of electrically stimulated penile erection. C6'
      generated NO, increased cGMP, and dose dependently increased NO metabolites. C6'
      treatment reversed abnormalities in key penile erection signaling molecules,
      including phosphodiesterase type 5, phosphorylated endothelial nitric oxide
      synthase, and phosphorylated vasodilator-stimulated phosphoprotein. In Sickle
      mice, C6' also attenuated the increased ROS markers gp91(phox), 4-hydroxynonenal,
      and 3-nitrotyrosine. Finally, C6' corrected the excessive priapic erection
      response of dNOS(-/-) mice. Exogenous sustained NO release from C6' corrects
      pathological erectile signaling in mouse models of priapism and suggests novel
      approaches to human therapy.

PMID- 24076964
TI  - Regulation of matrix metalloproteinase-1, -3, and -9 in Mycobacterium
      tuberculosis-dependent respiratory networks by the rapamycin-sensitive
      PI3K/p70(S6K) cascade.
AB  - This study was designed to investigate the role of the phosphatidyl inositol 3
      kinase (PI3K)/AKT/p70(S6K) signaling path on regulation of primary normal human
      bronchial epithelial cell-derived matrix metalloproteinase (MMP)-1, -3, and -9
      expression in tuberculosis (TB). These MMPs are key in pathological extracellular
      matrix degradation in TB. Normal human bronchial epithelials were stimulated with
      conditioned medium from monocytes infected with virulent TB (CoMTb) and
      components of the PI3K/AKT signaling pathway blocked using specific chemical
      inhibitors and siRNA. MMP gene expression was measured by RT-PCR and secretion by
      ELISA, luminex, or zymography. Phospho-p70 S6K was detected by Western blot
      analysis and activity blocked by rapamycin. Chemical blockade of the proximal
      catalytic PI3K p110 subunit augmented MMP-1 and MMP-9 in a dose-dependent manner
      (all P<0.001) but suppressed MMP-3 (P<0.01). Targeted siRNA studies identified
      the p110alpha isoform as key causing 5-fold increase in TB network-dependent MMP
      1 secretion to 4900 +/- 1100 pg/ml. Specific inhibition of the AKT node
      suppressed all 3 MMPs. Phospho-p70(S6K) was identified in the cellular model, and
      rapamycin, a p70(S6K) inhibitor, inhibited MMP-1 (P<0.001) and MMP-3 (P<0.01) but
      not MMP-9. Controls were epithelial cells that were unstimulated or exposed to
      conditioned medium from monocytes not exposed to TB. In summary, blockade of the
      proximal PI3K catalytic subunit increases MMP-1 and MMP-9, whereas rapamycin
      decreased both MMP-1 and MMP-3. The regulation of the PI3K path in TB is complex,
      MMP specific, and a potential immunotherapeutic target in diseases characterized
      by tissue destruction.

PMID- 24076966
TI  - Core-shell Si-N-doped C assembled via an oxidative template for lithium-ion
      anodes.
AB  - The Si-NC core-shell composite was synthesized by a modified oxidative template
      assembly route using a facile carbonization process. The images of the obtained
      Si-NC composites showed that an amorphous NC layer adsorbed stably and tightly on
      the nano-Si surface with an only several nanometers thickness to the formation of
      the Si-NC core-shell structure, which was beneficial for the electronic contact
      of Si nanoparticles. For the Si-NC-700 anode, it could be calculated that the
      initial charge capacity was 986.2 mA h g(-1) at a rate of 0.2 C. And it could
      still be kept at 764.4 mA h g(-1) over 100 cycles, with a little capacity loss of
      0.22% per cycle. Moreover, it was concluded that the Si-NC-700 anode could
      achieve a capacity of 790.8 mA h g(-1) for the first cycle, and significantly
      remain at 778.2 mA h g(-1) over 500 cycles at a rate of 0.5 C. These excellent
      electrochemical performances could probably be due to the N-doping generating the
      extrinsic defects and the absorption of Li ions, and hence result in a superior
      long-term cycling stability and rate capability. This suggests that the core
      shell Si-NC composite is a promising material for improving the electrochemical
      performance of lithium-ion anodes. 

PMID- 24076967
TI  - HIV RNA and genotype in resource-limited settings: can we do better?

PMID- 24076965
TI  - Dynamin-related protein 1 (Drp1)-mediated diastolic dysfunction in myocardial
      ischemia-reperfusion injury: therapeutic benefits of Drp1 inhibition to reduce
      mitochondrial fission.
AB  - Mitochondrial fission, regulated by dynamin-related protein-1 (Drp1), is a newly
      recognized determinant of mitochondrial function, but its contribution to left
      ventricular (LV) impairment following ischemia-reperfusion (IR) injury is
      unknown. We report that Drp1 activation during IR results in LV dysfunction and
      that Drp1 inhibition is beneficial. In both isolated neonatal murine
      cardiomyocytes and adult rat hearts (Langendorff preparation) mitochondrial
      fragmentation and swelling occurred within 30 min of IR. Drp1-S637 (serine 637)
      dephosphorylation resulted in Drp1 mitochondrial translocation and increased
      mitochondrial fission. The Drp1 inhibitor Mdivi-1 preserved mitochondrial
      morphology, reduced cytosolic calcium, and prevented cell death. Drp1 siRNA
      similarly preserved mitochondrial morphology. In Langendorff hearts, Mdivi-1
      reduced mitochondrial reactive oxygen species, improved LV developed pressure
      (92+/-5 vs. 28+/-10 mmHg, P<0.001), and lowered LV end diastolic pressure (10+/-1
      vs. 86+/-13 mmHg, P<0.001) following IR. Mdivi-1 was protective if administered
      prior to or following ischemia. Because Drp1-S637 dephosphorylation is
      calcineurin sensitive, we assessed the effects of a calcineurin inhibitor, FK506.
      FK506 treatment prior to IR prevented Drp1-S637 dephosphorylation and preserved
      cardiac function. Likewise, therapeutic hypothermia (30 degrees C) inhibited Drp1
      S637 dephosphorylation and preserved mitochondrial morphology and myocardial
      function. Drp1 inhibition is a novel strategy to improve myocardial function
      following IR.

PMID- 24076968
TI  - Extraordinary heterogeneity of virological outcomes in patients receiving highly
      antiretroviral therapy and monitored with the World Health Organization public
      health approach in sub-saharan Africa and southeast Asia.
AB  - BACKGROUND: The limited access to virological monitoring in developing countries
      is a major weakness of the current antiretroviral treatment (ART) strategy in
      these settings. We conducted a large cross-sectional study in Burkina Faso,
      Cameroon, Cote d'Ivoire, Senegal, Togo, Thailand, and Vietnam to assess
      virological failure and drug resistance mutations (DRMs) after 12 or 24 months of
      ART. METHODS: Between 2009 and 2011, we recruited adults attending ART centers 10
      14 months (the M12 group) or 22-26 months (M24 group) after initiating ART.
      Demographic and clinical data were collected on site, and viral load was
      measured. Samples with a viral load of >= 1000 copies/mL, considered as the
      failure threshold, were genotyped for drug resistance assessment. RESULTS:
      Overall, 3935 patients were recruited (2060 at M12 and 1875 at M24). Median ages
      varied from 32 to 42 years. Median CD4(+) T-cell counts at ART initiation were
      low (99-172 cells/uL). The main ART regimens included stavudine/zidovudine plus
      lamivudine plus nevirapine/efavirenz. Overall, virological failure frequency was
      11.1% for M12 patients and 12.4% for M24 patients, and 71.0% to 86.1% of these
      patients, respectively, had drug-resistant virus. Across sites, virological
      failure varied from 2.9% to 20.6% in M12 patients and from 3.7% to 26.0% in M24
      patients. Predominant DRMs were associated with ART regimens, but virus in
      several patients accumulated DRMs to drugs not received, such as abacavir,
      didanosine, tenofovir, etravirine, and rilpivirine. CONCLUSIONS: Our findings
      show heterogeneous virological failure and illustrate that, in addition to
      routine access to viral load, good management of ART programs is even more
      critical to improve treatment outcomes in resource-limited countries.

PMID- 24076970
TI  - Invasive Haemophilus influenzae type b disease in England and Wales: who is at
      risk after 2 decades of routine childhood vaccination?
AB  - BACKGROUND: The introduction of the Haemophilus influenzae serotype b (Hib)
      conjugate vaccine into national immunization has led to rapid and sustained
      declines in invasive Hib disease incidence across all age groups. In
      industrialized countries with established Hib vaccination programs, however,
      little is known about individuals who develop invasive Hib disease. This study
      describes the epidemiology of invasive Hib disease in England and Wales during
      2000-2012 and the clinical characteristics of laboratory-confirmed Hib cases
      diagnosed during 2009-2012. METHODS: Public Health England (PHE) conducts
      enhanced national surveillance of invasive Hib disease in England and Wales.
      Detailed clinical information was obtained for all laboratory-confirmed Hib cases
      diagnosed during 2009-2012. RESULTS: Invasive Hib disease in England and Wales
      has been declining since 2002, reaching its lowest incidence of 0.02 per 100 000
      (14 cases) in 2012. In children aged <5 years of age, Hib incidence was 0.06 per
      100 000 (2 cases), compared with 35.5 per 100 000 prior to routine Hib
      vaccination. Follow-up of all 106 case patients over the 4-year period revealed
      that most cases occurred in adults (73%) who often had preexisting medical
      conditions (77%) and presented with pneumonia (56%). The Hib-associated case
      fatality rate was 9.4% (10/106 cases). CONCLUSIONS: Control of Hib disease in
      England and Wales is currently the best that has been achieved since the
      introduction of routine Hib vaccination in 1992. Invasive Hib disease is no
      longer a major cause of acute bacterial meningitis in children but, instead,
      cases are more likely to present as pneumonia in older adults with comorbidities,
      similar to the less virulent nonencapsulated H. influenzae.

PMID- 24076969
TI  - Virological, serological, and antiviral studies in an imported human case of
      avian influenza A(H7N9) virus in Taiwan.
AB  - We describe the clinical course and virological characteristics of the first H7N9
      influenza case in a Taiwanese patient; this patient had detectable viruses in the
      airway for 2 weeks, during which time an oseltamivir resistance-associated R292K
      mutation rapidly emerged. Anti-H7N9 antibody was detected 21 days after onset of
      symptoms, when H7N9 viral load declined significantly. 

PMID- 24076971
TI  - Shift work and cognition in the Nurses' Health Study.
AB  - Rotating night-shift work, which can disrupt circadian rhythm, may adversely
      affect long-term health. Experimental studies indicate that circadian rhythm
      disruption might specifically accelerate brain aging; thus, we prospectively
      examined shift-work history at midlife as associated with cognitive function
      among older women in the Nurses' Health Study. Women reported their history of
      rotating night-shift work in 1988 and participated in telephone-based cognitive
      interviews between 1995 and 2001; interviews included 6 cognitive tests that were
      subsequently repeated 3 times, at 2-year intervals. We focused on shift work
      through midlife (here, ages 58-68 years) because cognitive decline is thought to
      begin during this period. Using multivariable-adjusted linear regression, we
      evaluated mean differences in both "average cognitive status" at older age
      (averaging cognitive scores from all 4 interviews) and rates of cognitive decline
      over time across categories of shift-work duration at midlife (none, 1-9, 10-19,
      or >=20 years). There was little association between shift work and average
      cognition in later life or between shift work and cognitive decline. Overall,
      this study does not clearly support the hypothesis that shift-work history in
      midlife has long-term effects on cognition in older adults. 

PMID- 24076972
TI  - Prospective study of venous thromboembolism in patients with head and neck cancer
      after surgery.
AB  - IMPORTANCE: Venous thromboembolism (VTE) is associated with significant morbidity
      and mortality in surgery patients, but little data exist on the incidence of VTE
      in head and neck cancer surgical patients. OBJECTIVE: To determine the incidence
      of VTE in postoperative patients with head and neck cancer. DESIGN, SETTING, AND
      PARTICIPANTS: A prospective study of 100 consecutive patients hospitalized at a
      tertiary care academic surgical center who underwent surgery to treat head and
      neck cancer. Routine chemoprophylaxis was not used. On postoperative day (POD) 2
      or 3, participants received clinical examination and duplex ultrasonographic
      evaluation (US). Participants with negative findings on clinical examination and
      US were followed up clinically; participants with evidence of deep venous
      thrombosis (DVT) or pulmonary embolism (PE) were given therapeutic
      anticoagulation. Participants with superficial VTE underwent repeated US on POD
      4, 5, or 6. Participants were monitored for 30 days after surgery. MAIN OUTCOME
      AND MEASURE: Total number of new cases of VTE (superficial and deep) identified
      within 30 days of surgery and confirmed on diagnostic imaging. RESULTS: Of the
      111 participants enrolled, 11 withdrew before completing the study; thus, 100
      participants were included. The overall incidence of VTE was 13%. Eight
      participants were identified with clinically significant VTE: 7 DVT and 1 PE. An
      additional 5 participants had asymptomatic lower extremity superficial VTE
      detected on US alone. Fourteen percent of patients received some form of
      postoperative anticoagulation therapy; the rate of bleeding complications in
      these patients (30.1%) was higher than that in patients without anticoagulation
      therapy (5.6%) (P = .01). CONCLUSIONS AND RELEVANCE: Hospitalized patients with
      head and neck cancer not routinely receiving anticoagulation therapy after
      surgery have an increased risk of VTE. Bleeding complications are elevated in
      patients receiving postoperative anticoagulation.

PMID- 24076973
TI  - Toward advancing nano-object count metrology: a best practice framework.
AB  - BACKGROUND: A movement among international agencies and policy makers to classify
      industrial materials by their number content of sub-100-nm particles could have
      broad implications for the development of sustainable nanotechnologies.
      OBJECTIVES: Here we highlight current particle size metrology challenges faced by
      the chemical industry due to these emerging number percent content thresholds,
      provide a suggested best-practice framework for nano-object identification, and
      identify research needs as a path forward. DISCUSSION: Harmonized methods for
      identifying nanomaterials by size and count for many real-world samples do not
      currently exist. Although particle size remains the sole discriminating factor
      for classifying a material as "nano," inconsistencies in size metrology will
      continue to confound policy and decision making. Moreover, there are concerns
      that the casting of a wide net with still-unproven metrology methods may stifle
      the development and judicious implementation of sustainable nanotechnologies.
      Based on the current state of the art, we propose a tiered approach for
      evaluating materials. To enable future risk-based refinements of these emerging
      definitions, we recommend that this framework also be considered in environmental
      and human health research involving the implications of nanomaterials.
      CONCLUSION: Substantial scientific scrutiny is needed in the area of nanomaterial
      metrology to establish best practices and to develop suitable methods before
      implementing definitions based solely on number percent nano-object content for
      regulatory purposes. Strong cooperation between industry, academia, and research
      institutions will be required to fully develop and implement detailed frameworks
      for nanomaterial identification with respect to emerging count-based metrics.

PMID- 24076974
TI  - An-1 encodes a basic helix-loop-helix protein that regulates awn development,
      grain size, and grain number in rice.
AB  - Long awns are important for seed dispersal in wild rice (Oryza rufipogon), but
      are absent in cultivated rice (Oryza sativa). The genetic mechanism involved in
      loss-of-awn in cultivated rice remains unknown. We report here the molecular
      cloning of a major quantitative trait locus, An-1, which regulates long awn
      formation in O. rufipogon. An-1 encodes a basic helix-loop-helix protein, which
      regulates cell division. The nearly-isogenic line (NIL-An-1) carrying a wild
      allele An-1 in the genetic background of the awnless indica Guangluai4 produces
      long awns and longer grains, but significantly fewer grains per panicle compared
      with Guangluai4. Transgenic studies confirmed that An-1 positively regulates awn
      elongation, but negatively regulates grain number per panicle. Genetic variations
      in the An-1 locus were found to be associated with awn loss in cultivated rice.
      Population genetic analysis of wild and cultivated rice showed a significant
      reduction in nucleotide diversity of the An-1 locus in rice cultivars, suggesting
      that the An-1 locus was a major target for artificial selection. Thus, we propose
      that awn loss was favored and strongly selected by humans, as genetic variations
      at the An-1 locus that cause awn loss would increase grain numbers and
      subsequently improve grain yield in cultivated rice. 

PMID- 24076975
TI  - The tomato Fni3 lysine-63-specific ubiquitin-conjugating enzyme and suv ubiquitin
      E2 variant positively regulate plant immunity.
AB  - The activation of an immune response in tomato (Solanum lycopersicum) against
      Pseudomonas syringae relies on the recognition of E3 ligase-deficient forms of
      AvrPtoB by the host protein kinase, Fen. To investigate the mechanisms by which
      Fen-mediated immunity is regulated, we characterize in this study a Fen
      interacting protein, Fni3, and its cofactor, S. lycoperiscum Uev (Suv). Fni3
      encodes a homolog of the Ubc13-type ubiquitin-conjugating enzyme that catalyzes
      exclusively Lys-63-linked ubiquitination, whereas Suv is a ubiquitin-conjugating
      enzyme variant. The C-terminal region of Fen was necessary for interaction with
      Fni3, and this interaction was required for cell death triggered by
      overexpression of Fen in Nicotiana benthamiana leaves. Fni3 was shown to be an
      active E2 enzyme, but Suv displayed no ubiquitin-conjugating activity; Fni3 and
      Suv together directed Lys-63-linked ubiquitination. Decreased expression of Fni3,
      another tomato Ubc13 homolog, Sl-Ubc13-2, or Suv in N. benthamiana leaves
      diminished cell death associated with Fen-mediated immunity and cell death
      elicited by several other resistance (R) proteins and their cognate effectors. We
      also discovered that coexpression of Fen and other R proteins/effectors with a
      Fni3 mutant that is compromised for ubiquitin-conjugating activity diminished the
      cell death. These results suggest that Fni3/Sl-Ubc13-2 and Suv regulate the
      immune response mediated by Fen and other R proteins through Lys-63-linked
      ubiquitination. 

PMID- 24076976
TI  - Repression of growth regulating factors by the microRNA396 inhibits cell
      proliferation by UV-B radiation in Arabidopsis leaves.
AB  - Because of their sessile lifestyle, plants are continuously exposed to solar UV-B
      radiation. Inhibition of leaf growth is one of the most consistent responses of
      plants upon exposure to UV-B radiation. In this work, we investigated the role of
      Growth-Regulating Factors (GRFs) and of microRNA miR396 in UV-B-mediated
      inhibition of leaf growth in Arabidopsis thaliana plants. We demonstrate that
      miRNA396 is upregulated by UV-B radiation in proliferating tissues and that this
      induction is correlated with a decrease in GRF1, GRF2, and GRF3 transcripts.
      Induction of miR396 results in inhibition of cell proliferation, and this outcome
      is independent of the UV-B photoreceptor UV resistance locus 8, as well as ATM
      AND RAD3-related and the mitogen-activated protein kinase MPK6, but is dependent
      on MPK3. Transgenic plants expressing an artificial target mimic directed against
      miR396 (MIM396) with a decrease in the endogenous microRNA activity or plants
      expressing miR396-resistant copies of several GRFs are less sensitive to this
      inhibition. Consequently, at intensities that can induce DNA damage in
      Arabidopsis plants, UV-B radiation limits leaf growth by inhibiting cell division
      in proliferating tissues, a process mediated by miR396 and GRFs.

PMID- 24076977
TI  - Plant callus: mechanisms of induction and repression.
AB  - Plants develop unorganized cell masses like callus and tumors in response to
      various biotic and abiotic stimuli. Since the historical discovery that the
      combination of two growth-promoting hormones, auxin and cytokinin, induces callus
      from plant explants in vitro, this experimental system has been used extensively
      in both basic research and horticultural applications. The molecular basis of
      callus formation has long been obscure, but we are finally beginning to
      understand how unscheduled cell proliferation is suppressed during normal plant
      development and how genetic and environmental cues override these repressions to
      induce callus formation. In this review, we will first provide a brief overview
      of callus development in nature and in vitro and then describe our current
      knowledge of genetic and epigenetic mechanisms underlying callus formation. 

PMID- 24076978
TI  - Establishing a framework for the Ad/abaxial regulatory network of Arabidopsis:
      ascertaining targets of class III homeodomain leucine zipper and KANADI
      regulation.
AB  - The broadly conserved Class III homeodomain leucine zipper (HD-ZIPIII) and KANADI
      transcription factors have opposing and transformational effects on polarity and
      growth in all tissues and stages of the plant's life. To obtain a comprehensive
      understanding of how these factors work, we have identified transcripts that
      change in response to induced HD-ZIPIII or KANADI function. Additional criteria
      used to identify high-confidence targets among this set were presence of an
      adjacent HD-ZIPIII binding site, expression enriched within a subdomain of the
      shoot apical meristem, mutant phenotype showing defect in polar leaf and/or
      meristem development, physical interaction between target gene product and HD
      ZIPIII protein, opposite regulation by HD-ZIPIII and KANADI, and evolutionary
      conservation of the regulator-target relationship. We find that HD-ZIPIII and
      KANADI regulate tissue-specific transcription factors involved in subsidiary
      developmental decisions, nearly all major hormone pathways, and new actors (such
      as indeterminate domain4) in the ad/abaxial regulatory network. Multiple feedback
      loops regulating HD-ZIPIII and KANADI are identified, as are mechanisms through
      which HD-ZIPIII and KANADI oppose each other. This work lays the foundation
      needed to understand the components, structure, and workings of the ad/abaxial
      regulatory network directing basic plant growth and development.

PMID- 24076980
TI  - Assessment of motor imagery in cerebral palsy via mental chronometry: the case of
      walking.
AB  - Recent studies show varying results on whether motor imagery capacity is
      compromised in individuals with cerebral palsy (CP). Motor imagery studies in
      children predominantly used the implicit hand laterality task. In this task
      participants judge the laterality of displayed hand stimuli. A more explicit way
      of studying motor imagery is mental chronometry. This paradigm is based on the
      comparison between the movement durations of actually performing a task and
      imagining the same task. The current study explored motor imagery capacity in CP
      by means of mental chronometry of a whole body task. Movement durations of 20
      individuals with CP (mean age=13 years, SD=3.6) were recorded in two conditions:
      actual walking and imagined walking. Six unique trajectories were used that
      varied in difficulty via manipulation of walking distance and path width. We
      found no main effect of condition (actual walking versus imagining) on movement
      durations. Difficulty of the walking trajectory did affect movement durations. In
      general, this was expressed by an increase in movement durations with increasing
      difficulty of the task. No interaction between task difficulty and movement
      condition was found. Our results show that task difficulty has similar effects on
      movement durations for both actual walking and imagined walking. These results
      exemplify that the tested individuals were able to use motor imagery in an
      explicit task involving walking. Previous studies using the implicit hand
      laterality task showed varying results on motor imagery capacity in CP. We
      therefore conclude that motor imagery capacity is task dependent and that an
      explicit paradigm as the one used in this study may reveal the true motor imagery
      capacity. The implications of these findings for the use of motor imagery
      training are discussed. 

PMID- 24076979
TI  - Dual role for phospholipid:diacylglycerol acyltransferase: enhancing fatty acid
      synthesis and diverting fatty acids from membrane lipids to triacylglycerol in
      Arabidopsis leaves.
AB  - There is growing interest in engineering green biomass to expand the production
      of plant oils as feed and biofuels. Here, we show that
      phospholipid:diacylglycerol acyltransferase1 (PDAT1) is a critical enzyme
      involved in triacylglycerol (TAG) synthesis in leaves. Overexpression of PDAT1
      increases leaf TAG accumulation, leading to oil droplet overexpansion through
      fusion. Ectopic expression of oleosin promotes the clustering of small oil
      droplets. Coexpression of PDAT1 with oleosin boosts leaf TAG content by up to
      6.4% of the dry weight without affecting membrane lipid composition and plant
      growth. PDAT1 overexpression stimulates fatty acid synthesis (FAS) and increases
      fatty acid flux toward the prokaryotic glycerolipid pathway. In the
      trigalactosyldiacylglycerol1-1 mutant, which is defective in eukaryotic thylakoid
      lipid synthesis, the combined overexpression of PDAT1 with oleosin increases leaf
      TAG content to 8.6% of the dry weight and total leaf lipid by fourfold. In the
      plastidic glycerol-3-phosphate acyltransferase1 mutant, which is defective in the
      prokaryotic glycerolipid pathway, PDAT1 overexpression enhances TAG content at
      the expense of thylakoid membrane lipids, leading to defects in chloroplast
      division and thylakoid biogenesis. Collectively, these results reveal a dual role
      for PDAT1 in enhancing fatty acid and TAG synthesis in leaves and suggest that
      increasing FAS is the key to engineering high levels of TAG accumulation in green
      biomass.

PMID- 24076981
TI  - Attentional lapse and inhibition control in adults with Williams Syndrome.
AB  - Research exploring cognitive processing associated with Williams Syndrome (WS)
      has suggested that executive functioning deficits exist across the developmental
      spectrum. Such executive functions include problem solving, planning, dividing
      attention and inhibiting responses. Within a framework of executive functions,
      the aim of the current study was to explore attentional lapse and inhibition
      skills in older adults with WS (n=20; aged 36-61 yr) and consider the
      implications of deficits within this group. Participants with WS were compared to
      typical adults of the same chronological age and typical older adults (aged
      65+yr) to consider attentional changes seen in the ageing process. The study
      employed a sustained attention to response task known to assess inhibition and
      attentional lapse but which had not previously been used with this population.
      Compared to both groups of typical matches, the results indicated atypicalities
      of attention and inhibition in adults with WS. Specifically, compared to the
      typical matches, adults with WS failed to withhold a response (showing inhibition
      deficits), had problems re-engaging attentional control processes after making an
      error and showed a generalised deficit of concentration and task engagement. We
      conclude that further attention should be paid to the cognitive capacity of older
      individuals with WS in order to consider the everyday challenges faced by this
      group and to provide adequate intervention and support for daily living.

PMID- 24076982
TI  - Further evaluation of a telephone technology for enabling persons with multiple
      disabilities and lack of speech to make phone contacts with socially relevant
      partners.
AB  - This study assessed whether a girl and a woman with multiple disabilities could
      (a) make phone contacts with relevant partners through a special telephone
      technology, and (b) enjoy their telephone-mediated communication with them. The
      technology involved a net-book computer, a global system for mobile communication
      modem (GSM), an optic microswitch, and specific software. The technology was
      programmed to present the names of the partners available for contact, and the
      participants could choose at each presentation sequence the one they wanted to
      contact with a simple microswitch response. Such response triggered the computer
      to place a phone call to that partner. Both participants (a) learned to use the
      technology quite rapidly to contact relevant partners and maintained the
      successful use of it over the intervention and post-intervention sessions, (b)
      showed high levels of indices of happiness during the phone calls as opposed to
      pre-baseline control sessions, and (c) showed preferences among the partners.
      Implications of the findings are discussed. 

PMID- 24076983
TI  - Incontinence in individuals with Angelman syndrome: a comparative study.
AB  - Frequency and type of incontinence and variables associated with incontinence
      were assessed in individuals with Angelman syndrome (AS; n=71) and in a matched
      control group (n=69) consisting of individuals with non-specific intellectual
      disability (ID). A Dutch version of the "Parental Questionnaire: Enuresis/Urinary
      Incontinence" (Beetz, von Gontard, & Lettgen, 1994) was administered and
      information on primary caretakers' perspectives regarding each individual's
      incontinence was gathered. Results show that diurnal incontinence and fecal
      incontinence during the day more frequently occurred in the control group than in
      the AS group. In both groups, nocturnal enuresis was the most common form of
      incontinence. More incontinence was seen in individuals with AS who were younger,
      had a lower level of adaptive functioning and/or had epilepsy. Individuals with
      AS were able to stay dry for longer periods of time than the controls and often
      showed both in-toilet urination and urinary accidents during the day, whereas
      accidents and correct voids during the day were more set apart in the control
      group. Also, persons with AS had a lower micturition frequency implying possible
      voiding postponement. Both groups showed high rates of LUTS (lower urinary tract
      symptoms) possibly indicative of functional bladder disorders such as voiding
      postponement, dysfunctional voiding, or even an underactive bladder. In general,
      most primary caretakers reported severe intellectual disability as the main cause
      for urinary incontinence. Based on these results incontinence does not appear to
      be part of the behavioral phenotype of Angelman syndrome. Therefore, pediatric or
      urologic diagnostics and treatment are recommended for all persons with
      incontinence and intellectual disability. Further implications for practice and
      research are given. 

PMID- 24076984
TI  - Diagnostic profiles of children with developmental dyslexia in a transparent
      orthography.
AB  - In the present study for 108 typical and 122 atypical Dutch readers in second
      grade, the accuracy and speed of decoding words and pseudowords, as well as the
      accuracy of spelling words were assessed along with four types of phonological
      precursor measures: rapid naming, verbal working memory, phoneme awareness and
      letter knowledge. The data show that the group being diagnosed as poor readers
      were significantly behind in all reading and spelling measures. It was also found
      that the criterion measures of reading and spelling explained already two third
      of the variance associated with the group distinction. Finally, we found word and
      pseudoword efficiency in the typical group to be explained by phonological
      awareness (spoonerism) and rapid naming of letters, word and pseudoword accuracy
      by phonological awareness, and spelling by phonological awareness and letter
      dictation. In the group of poor readers, a much greater variety of precursor
      measures was involved in explaining the variance in reading and spelling
      abilities. 

PMID- 24076985
TI  - ExpressionBlast: mining large, unstructured expression databases.

PMID- 24076986
TI  - Building an ENCODE-style data compendium on a shoestring.

PMID- 24076987
TI  - Genomics in the clouds.

PMID- 24076988
TI  - hiFRET: some tailwind for FRET resolves weak protein interactions.

PMID- 24076989
TI  - Recommendations for the design and analysis of epigenome-wide association
      studies.
AB  - Epigenome-wide association studies (EWAS) hold promise for the detection of new
      regulatory mechanisms that may be susceptible to modification by environmental
      and lifestyle factors affecting susceptibility to disease. Epigenome-wide
      screening methods cover an increasing number of CpG sites, but the complexity of
      the data poses a challenge to separating robust signals from noise. Appropriate
      study design, a detailed a priori analysis plan and validation of results are
      essential to minimize the danger of false positive results and contribute to a
      unified approach. Epigenome-wide mapping studies in homogenous cell populations
      will inform our understanding of normal variation in the methylome that is not
      associated with disease or aging. Here we review concepts for conducting a
      stringent and powerful EWAS, including the choice of analyzed tissue, sources of
      variability and systematic biases, outline analytical solutions to EWAS-specific
      problems and highlight caveats in interpretation of data generated from samples
      with cellular heterogeneity. 

PMID- 24076991
TI  - Commentary: lessons learned from case fatality risk estimates of 2009 pandemic
      influenza.

PMID- 24076990
TI  - Cas9 as a versatile tool for engineering biology.
AB  - RNA-guided Cas9 nucleases derived from clustered regularly interspaced short
      palindromic repeats (CRISPR)-Cas systems have dramatically transformed our
      ability to edit the genomes of diverse organisms. We believe tools and techniques
      based on Cas9, a single unifying factor capable of colocalizing RNA, DNA and
      protein, will grant unprecedented control over cellular organization, regulation
      and behavior. Here we describe the Cas9 targeting methodology, detail current and
      prospective engineering advances and suggest potential applications ranging from
      basic science to the clinic. 

PMID- 24076992
TI  - Direct and indirect effects of screening for Chlamydia trachomatis on the
      prevention of pelvic inflammatory disease: a mathematical modeling study.
AB  - BACKGROUND: Pelvic inflammatory disease (PID) results from the ascending spread
      of microorganisms, including Chlamydia trachomatis, to the upper genital tract.
      Screening could improve outcomes by identifying and treating chlamydial
      infections before they progress to PID (direct effect) or by reducing chlamydia
      transmission (indirect effect). METHODS: We developed a compartmental model that
      represents a hypothetical heterosexual population and explicitly incorporates
      progression from chlamydia to clinical PID. Chlamydia screening was introduced,
      with coverage increasing each year for 10 years. We estimated the separate
      contributions of the direct and indirect effects of screening on PID cases
      prevented per 100,000 women. We explored the influence of varying the time point
      at which clinical PID could occur and of increasing the risk of PID after
      repeated chlamydial infections. RESULTS: The probability of PID at baseline was
      3.1% by age 25 years. After 5 years, the intervention scenario had prevented 187
      PID cases per 100,000 women and after 10 years 956 PID cases per 100,000 women.
      At the start of screening, most PID cases were prevented by the direct effect.
      The indirect effect produced a small net increase in PID cases, which was
      outweighed by the effect of reduced chlamydia transmission after 2.2 years. The
      later that progression to PID occurs, the greater the contribution of the direct
      effect. Increasing the risk of PID with repeated chlamydial infection increases
      the number of PID cases prevented by screening. CONCLUSIONS: This study shows the
      separate roles of direct and indirect PID prevention and potential harms, which
      cannot be demonstrated in observational studies.

PMID- 24076993
TI  - Air pollution from incinerators and reproductive outcomes: a multisite study.
AB  - BACKGROUND: The few studies that have investigated the relationship between
      emissions from municipal solid-waste incinerators and adverse pregnancy outcomes
      have had conflicting results. We conducted a study to assess the effects of air
      emissions from the eight incinerators currently in operation in the Emilia
      Romagna Region of Italy on reproductive outcomes (sex ratio, multiple births,
      preterm births, and small for gestational age [SGA] births). METHODS: We
      considered all births (n = 21,517) to women residing within a 4-km radius of an
      incinerator at the time of delivery during the period 2003-2010 who were
      successfully linked to the Delivery Certificate database. This source also
      provided information on maternal characteristics and deliveries. Each newborn was
      georeferenced and characterized by a specific level of exposure to incinerator
      emissions, categorized in quintiles of PM10, and other sources of pollution (NOx
      quartiles), evaluated by means of ADMS-Urban system dispersion models. We ran
      logistic regression models for each outcome, adjusting for exposure to other
      pollution sources and maternal covariates. RESULTS: Incinerator pollution was not
      associated with sex ratio, multiple births, or frequency of SGA. Preterm delivery
      increased with increasing exposure (test for trend, P < 0.001); for the highest
      versus the lowest quintile exposure, the odds ratio was 1.30 (95% confidence
      interval = 1.08-1.57). A similar trend was observed for very preterm babies.
      Several sensitivity analyses did not alter these results. CONCLUSIONS: Maternal
      exposure to incinerator emissions, even at very low levels, was associated with
      preterm delivery.

PMID- 24076994
TI  - Commentary: case-control studies of screening for colorectal cancer: tailoring
      the design and analysis to the specific research question.

PMID- 24076996
TI  - Air pollution and liver enzymes.

PMID- 24076995
TI  - A conversation with Joseph F. Fraumeni, Jr. Interviewed by Robert N. Hoover.

PMID- 24076997
TI  - Relative risks from case-population data.

PMID- 24076998
TI  - Sufficient-cause modeling with matched data using SAS.

PMID- 24076999
TI  - Reporting instrumental variable analyses.

PMID- 24077000
TI  - Big data in epidemiology: too big to fail?

PMID- 24077001
TI  - Big data in epidemiology: too big to fail?

PMID- 24077002
TI  - Glycol ethers and congenital malformations.

PMID- 24077003
TI  - Glycol ethers and congenital malformations.

PMID- 24077004
TI  - Contrast-enhanced imaging of SPIO-labeled platelets using magnetomotive
      ultrasound.
AB  - The ability to image platelets in vivo can provide insight into blood clotting
      processes and coagulopathies, and aid in identifying sites of vascular
      endothelial damage related to trauma or cardiovascular disease. Toward this end,
      we have developed a magnetomotive ultrasound (MMUS) system that provides contrast
      enhanced imaging of superparamagnetic iron oxide (SPIO) labeled platelets via
      magnetically-induced vibration. Platelets are a promising platform for functional
      imaging contrast because they readily take up SPIOs and are easily harvested from
      blood. Here we report a novel MMUS system that accommodates an arbitrarily thick
      sample while maintaining portability. We employed a frequency- and phase-locked
      motion detection algorithm based on bandpass filtering of the differential RF
      phase, which allows for the detection of sub-resolution vibration amplitudes on
      the order of several nanometers. We then demonstrated MMUS in homogenous tissue
      phantoms at SPIO concentrations as low as 0.09 mg ml(-1) Fe (p < 0.0001, n = 6, t
      test). Finally, we showed that our system is capable of three-dimensional imaging
      of a 185 uL simulated clot containing SPIO-platelets. This highlights the
      potential utility for non-invasive imaging of platelet-rich clots, which would
      constitute a fundamental advance in technology for the study of hemostasis and
      detection of clinically relevant thrombi. 

PMID- 24077006
TI  - Clinical introduction to the hyaluronic acid dermal filler using cohesive
      polydensified matrix technology. Foreword.

PMID- 24077005
TI  - Musculoskeletal pain in overweight and obese children.
AB  - This review seeks to provide a current overview of musculoskeletal pain in
      overweight and obese children. Databases searched were Academic Search Complete,
      CINAHL, Medline, Proquest Health and Medical Complete, Scopus, Google Scholar,
      SPORTDiscuss and Trove for studies published between 1 January 2000 and 30
      December 2012. We used a broad definition of children within a 3- to 18-year age
      range. The search strategy included the following terms: obesity, morbid obesity,
      overweight, pain, musculoskeletal pain, child, adolescent, chronic pain, back
      pain, lower back pain, knee pain, hip pain, foot pain and pelvic pain. Two
      authors independently assessed each record, and any disagreement was resolved by
      the third author. Data were analysed using a narrative thematic approach owing to
      the heterogeneity of reported outcome measures. Ninety-seven records were
      initially identified using a variety of terms associated with children, obesity
      and musculoskeletal pain. Ten studies were included for thematic analysis when
      predetermined inclusion criteria were applied. Bone deformity and dysfunction,
      pain reporting and the impact of children being overweight or obese on physical
      activity, exercise and quality of life were the three themes identified from the
      literature. Chronic pain, obesity and a reduction in physical functioning and
      activity may contribute to a cycle of weight gain that affects a child's quality
      of life. Future studies are required to examine the sequela of overweight and
      obese children experiencing chronic musculoskeletal pain. 

PMID- 24077007
TI  - Molecular weight analyses and enzymatic degradation profiles of the soft-tissue
      fillers Belotero Balance, Restylane, and Juvederm Ultra.
AB  - BACKGROUND: In this study, the authors sought to determine the molecular weight
      distribution of three hyaluronic acids-Belotero Balance, Restylane, and Juvederm
      Ultra-and their rates of degradation following exposure to hyaluronidase. Lot
      consistency of Belotero Balance also was analyzed. METHODS: Three lots of
      Belotero Balance were analyzed using liquid chromatography techniques. The
      product was found to have high-molecular-weight and low-molecular-weight species.
      One lot of Belotero Balance was compared to one lot each of Juvederm Ultra and
      Restylane. Molecular weights of the species were analyzed. The hyaluronic acids
      were exposed to ovine testicular hyaluronidase at six time points-baseline and
      0.5, 1, 2, 6, and 24 hours-to determine degradation rates. RESULTS: Belotero
      Balance lots were remarkably consistent. Belotero Balance had the largest high
      molecular-weight species, followed by Juvederm Ultra and Restylane (p < 0.001).
      Low-molecular-weight differences among all three hyaluronic acids were not
      statistically significant. Percentages of high-molecular-weight polymer differ
      among the three materials, with Belotero Balance having the highest fraction of
      high-molecular-weight polymer. Degradation of the high-molecular-weight species
      over time showed different molecular weights of the high-molecular-weight
      fraction. Rates of degradation of the hyaluronic acids following exposure to
      ovine testicular hyaluronidase were similar. All hyaluronic acids were fully
      degraded at 24 hours. CONCLUSIONS: Fractions of high-molecular-weight polymer
      differ across the hyaluronic acids tested. The low-molecular-weight differences
      are not statistically significant. The high-molecular-weight products have
      different molecular weights at the 0.5- and 2-hour time points when exposed to
      ovine testicular hyaluronidase and are not statistically different at 24 hours.

PMID- 24077008
TI  - Review of key Belotero Balance safety and efficacy trials.
AB  - Belotero Balance is a novel highly cross-linked hyaluronic acid that uses
      cohesive polydensified matrix technology to achieve cohesive gel; improved
      adaptation by the dermis; and a soft, smooth fill. Several studies have now
      compared Belotero Balance to bovine collagen and other hyaluronic acids. Two
      pivotal studies demonstrated the noninferiority and superiority of Belotero
      Balance to bovine collagen. In the first study, more than half of the patients
      maintained optimal correction at 6 months on the Belotero-treated side of the
      face. The second of those two studies followed patients to week 96 and
      demonstrated that the effects of Belotero Balance in this long-term, open-label
      study persisted in the majority of subjects without repeated treatment for at
      least one interval of 48 weeks. The filler was well tolerated, with only one of
      34 total adverse events (injection-site bruising) considered to be related to the
      study device. A third study compared the safety and efficacy of other hyaluronic
      acids (i.e., Juvederm and Restylane) with Belotero Balance. In this study, the
      safety profiles of all three hyaluronic acids were generally favorable, with site
      specific adverse events mild to moderate and comparable across each hyaluronic
      acid. Aesthetic results were also similar, although Belotero Balance resulted in
      greater evenness than Restylane at 4 weeks by one indicator used in the study.
      Finally, a 5-year retrospective safety review of 317 patients treated with
      Belotero Balance over a 5-year period revealed no severe adverse events in any
      patients, including the absence of persistent nodules or granulomas.

PMID- 24077010
TI  - A multicenter study of the safety and effectiveness of hyaluronic acid with a
      cohesive polydensified matrix for treatment of nasolabial folds in subjects with
      Fitzpatrick skin types IV, V, and VI.
AB  - BACKGROUND: Although the use of the hyaluronic acid with cohesive polydensified
      matrix hyaluronic acid has been well explored in subjects with lighter skin
      (i.e., Fitzpatrick skin types I, II, and III), further exploration in subjects
      with Fitzpatrick skin types IV, V, and IV is warranted. The primary purpose of
      the study was to assess the safety of a cohesive polydensified matrix hyaluronic
      acid in the correction of nasolabial folds in subjects with Fitzpatrick skin
      types IV, V and VI, especially assessment of hyperpigmentation, hypopigmentation,
      and scarring. Effectiveness was also assessed. METHODS: A total of 93 subjects
      were enrolled in this 24-week investigation at three sites in the United States.
      All were injected bilaterally for nasolabial fold correction with cohesive
      polydensified matrix hyaluronic acid. Assessments included the recording of
      adverse events; injected volumes; wrinkle severity ratings; and global aesthetic
      improvement by evaluating investigators, treating investigators, and study
      subjects. RESULTS: Injection of cohesive polydensified matrix hyaluronic acid for
      the treatment of nasolabial folds in subjects with Fitzpatrick skin types IV, V,
      and VI showed no evidence of an association with hypopigmentation,
      hyperpigmentation, or scarring. Adverse events reported were typical of dermal
      filler injections with respect to type, rate, duration, and severity. CONCLUSION:
      Cohesive polydensified matrix hyaluronic acid is a safe and well-tolerated dermal
      filler for subjects with Fitzpatrick skin types IV, V, and VI.

PMID- 24077011
TI  - A problem-oriented approach to nodular complications from hyaluronic acid and
      calcium hydroxylapatite fillers: classification and recommendations for
      treatment.
AB  - BACKGROUND: Hyaluronic acid and calcium hydroxylapatite fillers are generally
      safe, efficacious, and well tolerated. However, complications are inevitable, as
      with any medical procedure. Nodules at the site of filler implantation may pose
      the greatest challenge, as treatment is often empiric and can be influenced by
      misconceptions. METHODS: Hyaluronic acid and calcium hydroxylapatite filler
      nodules, with or without inflammation, may form at various times during and after
      injection. The probable causes of these complications are described. Clinicians
      can benefit from a problem-oriented approach to their diagnosis and management.
      The need to consider common causes--notably, infection--before rare ones, such as
      hypersensitivity to filler material, is discussed. RESULTS: Better understanding
      of the possible causes of hyaluronic acid and calcium hydroxylapatite filler
      nodules effectively guides treatment and prevents underestimation of the role of
      contamination-including mycobacteria-in the pathogenesis of inflammatory nodules.
      It can also inform preventative strategies. The authors advocate ultrasonographic
      imaging for patients with persistent nodules, to help determine the precise
      nature and location of the implanted materials. CONCLUSIONS: When used
      appropriately, hyaluronic acid and calcium hydroxylapatite fillers have low
      complication rates. Filler nodules are often treated without full evaluation of
      possible causes. A problem-oriented approach that does not overlook the most
      common causes could improve the outcome of these unfortunate events and help
      prevent their occurrence and/or recurrence. Complications from currently
      available hyaluronic acid and calcium hydroxylapatite fillers are typically
      related to aspects of the injection procedure, such as suboptimal technique and
      bacterial contamination, rather than to the products themselves.

PMID- 24077012
TI  - A blanching technique for intradermal injection of the hyaluronic acid Belotero.
AB  - With the proliferation of dermal fillers in the aesthetic workplace have come
      instructions from various manufacturers regarding dermal placement. Determination
      of injection needle location in the dermis has in large part been based on
      physician expertise, product and needle familiarity, and patient-specific skin
      characteristics. An understanding of the precise depth of dermal structures may
      help practitioners improve injection specificity. Unlike other dermal fillers
      that suggest intradermal and deep dermal injection planes, a new hyaluronic acid
      with a cohesive polydensified matrix may be more appropriate for the superficial
      dermis because of its structure and its high degree of integration into the
      dermis. To that end, the authors designed a small study to quantify the depth of
      the superficial dermis by means of ultrasound and histology. Using ultrasound
      resources, the authors determined the depths of the epidermis, the dermis, and
      the reticular dermis in the buttocks of six patients; the authors then
      extrapolated the depth of the superficial reticular dermis. Histologic studies of
      two of the patients showed full integration of the product in the reticular
      dermis. Following determination of injection depths and filler integration, the
      authors describe a technique ("blanching") for injection of the cohesive
      polydensified matrix hyaluronic acid into the superficial dermis. At this time,
      blanching is appropriate only for injection of the cohesive polydensified matrix
      hyaluronic acid known as Belotero Balance in the United States, although it may
      have applications for other hyaluronic acid products outside of the United
      States.

PMID- 24077013
TI  - Biophysical characteristics of hyaluronic acid soft-tissue fillers and their
      relevance to aesthetic applications.
AB  - BACKGROUND: The purpose of this study was to present new rheologic data for
      hyaluronic acid filler products, correlate them with recent tissue integration
      studies, and provide a scientific rationale for selecting appropriate products
      for volume replacement within different tissue levels and anatomical zones. A
      brief overview of the methodology of filler rheology studies and data analysis is
      provided. METHODS: Six U.S. Food and Drug Administration-approved, cross-linked,
      nonanimal-derived hyaluronic acid filler products and one hyaluronic acid product
      approved in Europe and elsewhere were studied: one cohesive polydensifiedmatrix
      hyaluronic acid (Belotero Balance, also known as Belotero Basic), two Hylacross
      hyaluronicacids (Juvederm Ultra and Juvederm Ultra Plus), one Vycross hyaluronic
      acid (Juvederm Voluma), and three nonanimal stabilized hyaluronic acids (Perlane,
      Restylane and Restylane SubQ) [corrected].The elastic modulus, complex viscosity,
      and viscous modulus of each filler gel were quantified. Tan delta for each filler
      gel and also for calcium hydroxylapatite filler (Radiesse) was calculated at 0.7
      Hz. RESULTS: Cohesive polydensified matrix hyaluronic acid (Belotero Balance) has
      the lowest elasticity and viscosity and the highest tan delta. This predicts its
      soft, flowing qualities and correlates with its homogeneous pattern of tissue
      integration after intradermal implantation. Nonanimal stabilized hyaluronic acid
      (Perlane and Restylane) has the highest elasticity and viscosity and low tan
      delta. This predicts its firm, less flowing qualities and correlates with a bolus
      like pattern of tissue integration. Hylacross hyaluronic acid (Juvederm) has
      intermediate elasticity, viscosity, and tan delta, correlating with its
      intermediate pattern of tissue integration. CONCLUSIONS: Rheologic evaluation
      reliably predicts tissue integration patterns and appropriate clinical
      applications of the studied fillers. Paradigms of layered filler placement can be
      designed to optimally address individual patient need.

PMID- 24077014
TI  - Clinical application and assessment of Belotero: a roundtable discussion.
AB  - In this final article for the Supplement, the authors address the physical and
      aesthetic characteristics of the latest hyaluronic acid, Belotero Balance. Topics
      include unique characteristics of the hyaluronic acid, aesthetic indications,
      administration techniques, adverse events, and differences between Belotero and
      other hyaluronic acids. The article closes with a brief discussion about
      nomenclature of hyaluronic acid products.

PMID- 24077015
TI  - Chromosome position at the spindle equator is regulated by chromokinesin and a
      bipolar microtubule array.
AB  - The chromosome alignment is mediated by polar ejection and poleward forces acting
      on the chromosome arm and kinetochores, respectively. Although components of the
      motile machinery such as chromokinesin have been characterized, their dynamics
      within the spindle is poorly understood. Here we show that a quantum dot (Qdot)
      binding up to four Xenopus chromokinesin (Xkid) molecules behaved like a nanosize
      chromosome arm in the meiotic spindle, which is self-organized in cytoplasmic egg
      extracts. Xkid-Qdots travelled long distances along microtubules by changing
      several tracks, resulting in their accumulation toward and distribution around
      the metaphase plate. The analysis indicated that the direction of motion and
      velocity depend on the distribution of microtubule polarity within the spindle.
      Thus, this mechanism is governed by chromokinesin motors, which is dependent on
      symmetrical microtubule orientation that may allow chromosomes to maintain their
      position around the spindle equator until correct microtubule-kinetochore
      attachment is established. 

PMID- 24077016
TI  - Analyzing discharge strategies during acute care: a discrete-event simulation
      study.
AB  - BACKGROUND: We developed a discrete-event simulation model of patient pathway
      through an acute care hospital that comprises an ED and several inpatient units.
      The effects of discharge timing on ED waiting and boarding times, ambulance
      diversions, leave without treatment, and readmissions were explicitly modeled. We
      then analyzed the impact of 1 static and 2 proactive discharge strategies on
      these system outcomes. RESULTS: Our analysis indicated that although the 2
      proactive discharge strategies significantly reduced ED waiting and boarding
      times, and several other measures, compared with the static strategy (P < 0.01),
      the number of readmissions increased substantially. Further analysis indicated
      that these findings are sensitive to changes in patient arrival rate and
      conditions for ambulance diversion. CONCLUSIONS: Determining the appropriate time
      to discharge patients not only can affect individual patients' health outcomes,
      but also can affect various aspects of the hospital. The study improves our
      understanding of how individual inpatient discharge decisions can be objectively
      viewed in terms of their impact on other operations, such as ED crowding and
      readmission, in an acute care hospital.

PMID- 24077017
TI  - Altered levels of amyloid precursor protein intracellular domain-interacting
      proteins in Alzheimer disease.
AB  - BACKGROUND: The amyloid precursor protein intracellular domain (AICD) is an
      intrinsically unstructured molecule with functional promiscuity that plays an
      important role in determining the fate of the neurons during its degeneration.
      Its association with Alzheimer disease (AD) recently played a key role in
      propelling scientists to choose AICD as a major molecule of interest. Although
      several studies have been conducted elucidating AICD's participation in inducing
      neurodegenerative outcomes in AD condition, much remains to be deciphered
      regarding the linkage of AICD with cellular pathways in the AD scenario. RESULTS:
      In the present study, we have pulled down interactors of nonphosphorylated AICD
      from the cerebrospinal fluid of AD subjects, identified them by matrix assisted
      laser desorption ionization mass spectrometry, and subsequently studied the
      differential expression of these interactors in AD and control cases by 2
      dimensional difference gel electrophoresis. The study has yielded some AICD
      interactors that are differentially expressed in the AD cases and are involved in
      diverse cellular functions. CONCLUSIONS: This proteomic-based approach highlights
      the first step in finding the possible cellular pathways engaged in AD
      pathophysiology on the basis of interaction of one or more of their members with
      AICD.

PMID- 24077018
TI  - Neuropsychological deficits associated with route learning in Alzheimer disease,
      MCI, and normal aging.
AB  - BACKGROUND: The background of route learning (RL) abilities in Alzheimer disease
      (AD), mild cognitive impairment (MCI), and normal aging needs further study. We
      searched for neuropsychological and demographical predictors of RL impairment.
      METHODS: RL was investigated in a clinical study including subjects classified as
      early AD (n=37), MCI (n=34), and aged normal controls (n=46). An ecological
      assessment procedure of RL was employed and landmarks learning and navigational
      abilities were evaluated. The consortium to establish a registry of Alzheimer's
      disease test battery was used for neuropsychological assessment. RESULTS: Almost
      all AD patients, and most subjects with MCI misidentified landmarks and made
      navigational errors when following the route without assistance. Moreover, a
      small subgroup of normal controls also had problems with RL. Poor RL performance
      was best predicted by impairments in memory and executive functions. CONCLUSIONS:
      RL impairment is common in early AD and MCI, and is occasionally also found in
      normal elderly subjects. Its characteristic appearance is a combination of poor
      landmark recognition and defective directional guidance. Poor RL can be predicted
      by neuropsychological testing. In MCI and in a subset of normal aged persons, RL
      impairment may herald incipient dementia.

PMID- 24077019
TI  - Electrochemical discharge of nanocrystalline magnetite: structure analysis using
      X-ray diffraction and X-ray absorption spectroscopy.
AB  - Magnetite (Fe3O4) is an abundant, low cost, environmentally benign material with
      potential application in batteries. Recently, low temperature coprecipitation
      methods have enabled preparation of a series of nanocrystalline magnetite samples
      with a range of crystallite sizes. Electrochemical cells based on Li/Fe3O4 show a
      linear increase in capacity with decreasing crystallite size at voltages >=1.2 V
      where a 2* capacity improvement relative to commercial (26.2 nm) magnetite is
      observed. In this report, a combination of X-ray powder diffraction (XRD) and X
      ray absorption spectroscopy (XAS) is used to measure magnetite structural changes
      occurring upon electrochemical reduction, with parent Fe3O4 crystallite size as a
      variable. Notably, XAS provides evidence of metallic iron formation at high
      levels of electrochemical reduction. 

PMID- 24077021
TI  - The "Fenton like" reaction of MoO43- involves two H2O2 molecules.
AB  - Surprisingly the oxidation of MoO4(3-) by H2O2 involves two H2O2 molecules. It is
      proposed that generally when the reaction of a reducing agent with H2O2, to form
      a single electron oxidized product and a hydroxyl radical, is endothermic the
      reaction involves more than one H2O2 molecule. 

PMID- 24077020
TI  - Production of functional gametes from cryopreserved primordial germ cells of the
      Japanese quail.
AB  - The Japanese quail (Coturnix japonica) is a valuable bird as both an experimental
      animal, for a wide range of scientific disciplines, and an agricultural animal,
      for the production of eggs and meat. Cryopreservation of PGCs would be a feasible
      strategy for the conservation of both male and female fertility cells in Japanese
      quail. However, the effects of freeze-thaw treatment on viability, migration
      ability and germline transmission ability of quail PGCs still remain unclear. In
      the present study, male and female PGCs were isolated from the blood of 2-day-old
      embryos, which were cooled by slow freezing and then cryopreserved at -196 C for
      77-185 days, respectively. The average recovery rate of PGCs after freeze-thawing
      was 47.0%. The viability of PGCs in the frozen group was significantly lower than
      that of the control group (P<0.05) (85.5% vs. 95.1%). Both fresh and Frozen
      thawed PGCs that were intravascularly transplanted into recipient embryos
      migrated toward and were incorporated into recipient gonads, although the number
      of PGCs settled in the gonads was 48.5% lower in the frozen group than in the
      unfrozen control group (P<0.05). Genetic cross analysis revealed that one female
      and two male recipients produced live progeny derived from the frozen-thawed
      PGCs. The frequency of donor-derived offspring was slightly lower than that of
      unfrozen controls, but the difference was not significant (4.0 vs. 14.0%). These
      results revealed that freeze-thaw treatment causes a decrease in viability,
      migration ability and germline transmission ability of PGCs in quail. 

PMID- 24077022
TI  - Cu(II) complex formation by ACES buffer.
AB  - ACES (N-(2-Acetamido)-2-aminoethanesulfonic acid), a popular Good's buffer, binds
      Cu(II) ions with a moderate affinity. Although this interaction was the subject
      of previous studies, no consensus in the literature was found. We used
      potentiometry to establish binding constants, and controlled the potentiometric
      model selection and binding constant calculations by UV-vis spectroscopy. As a
      result, we obtained a consistent set of complex stoichiometries and binding
      constants in this system, which contains Cu(2+), CuL(+), CuL2, CuH-1L2(-1) and
      CuH(-)2L2(-2) complexes. The negative indexes at H atoms in these formulae denote
      the Cu(II) assisted deprotonation of the amide nitrogen present in the ACES
      molecule. The affinity of ACES for Cu(II) strongly depends on the concentration
      and ACES:Cu(II) ratio, reaching submicromolar apparent affinities at ratios
      higher than 100. These results will enable more accurate determinations of
      biologically relevant stability constants of Cu(II) complexes using ACES buffer. 

PMID- 24077023
TI  - Impact of surgical resection on survival in patients with advanced head and neck
      cancer involving the carotid artery.
AB  - IMPORTANCE: The present study addresses the survival benefit of aggressive
      surgical treatment of head and neck cancer involving the carotid artery.
      OBJECTIVE: To assess survival outcomes in patients treated for advanced squamous
      cell carcinoma involving the carotid artery using different treatment strategies.
      DESIGN, SETTING, AND PARTICIPANTS: Retrospective study at a tertiary care center
      of 44 consecutive patients with squamous cell carcinoma involving the carotid
      artery from 2005 to 2012 with a median follow-up of 12 months. The radiologist
      was blinded to the outcome of surgical procedures. INTERVENTIONS: Surgery with or
      without radiotherapy, and definitive chemoradiation. MAIN OUTCOMES AND MEASURES:
      Overall survival and rates of locoregional and distant failures. The hypothesis
      was formulated before data collection. RESULTS: Of 44 patients, 35 (80%) were
      treated with curative intent with surgery with or without adjuvant therapy (n =
      27 [61%]) or definitive chemoradiation therapy (n = 8 [18%]), while 9 patients
      (21%) were treated in a palliative fashion. Patients treated with curative intent
      had improved overall survival (median survival, 13.5 months) compared with the
      palliative group (median survival, 3.6 months) (P = .001). Of patients treated
      with curative intent, those with previously untreated disease (n = 14 [40%]) had
      an improved outcome relative to patients with recurrent or persistent disease (n
      = 21 [60%]), with median survival of 38.7 and 9.6 months, respectively (P =
      .008). Patients were treated with curative intent using 3 different treatment
      strategies (ie, carotid artery resection with or without reanastamosis) (n = 6
      [17%]), curative peeling with or without adjuvant therapy (n = 21 [ 60%]), and
      definitive chemoradiation therapy (n = 8 [23%]). Survival outcome was not
      significantly different between subgroups treated with curative intention (P =
      .47). When reviewed by a head and neck radiologist in a blinded fashion (n = 30),
      preintervention imaging had a positive predictive value of 72.7% for
      resectability of cancer involving the carotid artery. In cases with almost
      circumferential involvement (>270 degrees ) and narrowing of the carotid artery,
      the disease was unresectable (n = 3). CONCLUSIONS AND RELEVANCE: Advanced head
      and neck cancer involving the carotid artery can be treated with curative intent
      with favorable results in most patients. If disease burden merits, an aggressive
      approach involving resection with or without reanastamosis of the carotid artery
      can be used without significant added morbidity.

PMID- 24077024
TI  - Racial and Gender Discrimination in the Stress Process: Implications for African
      American Women's Health and Well-Being.
AB  - In recent decades, sociologists have increasingly adopted an intersectionality
      framework to explore and explain the complex and interconnected nature of
      inequalities in the areas of race, class, and gender. Using an inclusion-centered
      approach and a sample of 204 low-socioeconomic-status (SES) African American
      women, the authors theorize and explore the role of racial and gender
      discrimination in the stress process. Analyses examine relationships between
      social stressors (racial and gender discrimination) and individual stressors
      occurring in each of six distinct social contexts. Furthermore, the authors
      evaluate the effects of racial and gender discrimination as compared to
      individual stressors on three indicators of mental health and well-being.
      Findings suggest that racial and gender discrimination increases risk for poor
      health and low well-being, working both directly and indirectly through increased
      vulnerability to individual stressors. This research demonstrates the value of a
      more comprehensive study of stressors that influence the health of low-SES
      African American women and other multiply disadvantaged groups.

PMID- 24077025
TI  - IN THE TRANSLATOR'S WORKSHOP.
AB  - Hunayn ibn Ishaq's Arabic translation of Galen's commentary on the Hippocratic
      Epidemics is an invaluable source for our knowledge of Galenic medicine and its
      transmission history, not least because much of it is extant only in Arabic. Its
      importance for the Arabic medical tradition is amply attested in the later
      medical literature. It also tells us much about the methods and self-image of
      contemporary translators. Throughout the translation, we find remarks by Hunayn
      discussing the quality of his source text, his own interpretation and also his
      attempts to reconstruct problematic or damaged passages. Based on an edition of
      these notes, their analysis and comparison to similar texts and Galen's own
      thought on editing and interpreting difficult medical texts, this article aims to
      situate Hunayn's methods in the context of the Greek-Arabic translation movement.
      It argues that his approach differs in important respects from that of preceding
      Greek-Arabic and Greek-Syriac translators and that he was indebted to Galen not
      just as a physician, but also as a translator and exegete.

PMID- 24077026
TI  - Effects of MRTI sampling characteristics on estimation of HIFU SAR and tissue
      thermal diffusivity.
AB  - While the non-invasive and three-dimensional nature of magnetic-resonance
      temperature imaging (MRTI) makes it a valuable tool for high-intensity focused
      ultrasound (HIFU) treatments, random and systematic errors in MRTI measurements
      may propagate into temperature-based parameter estimates used for pretreatment
      planning. This study assesses the MRTI effects of zero-mean Gaussian noise (SD =
      0.0-2.0  degrees C), temporal sampling (tacq = 1.0-8.0 s), and spatial averaging
      (Res = 0.5-2.0 mm isotropic) on HIFU temperature measurements and temperature
      based estimates of the amplitude and full width half maximum (FWHM) of the HIFU
      specific absorption rate and of tissue thermal diffusivity. The ultrasound beam
      used in simulations and ex vivo pork loin experiments has lateral and axial FWHM
      dimensions of 1.4 mm and 7.9 mm respectively. For spatial averaging simulations,
      beams with lateral FWHM varying from 1.2-2.2 mm are also assessed. Under noisy
      conditions, parameter estimates are improved by fitting to data from larger voxel
      regions. Varying the temporal sampling results in minimal changes in measured
      temperatures (<2% change) and parameter estimates (<5% change). For the HIFU
      beams studied, a spatial resolution of 1 * 1 * 3 mm(3) or smaller is required to
      keep errors in temperature and all estimated parameters less than 10%. By
      quantifying the errors associated with these sampling characteristics, this work
      provides researchers with appropriate MRTI conditions for obtaining estimates of
      parameters essential to pretreatment modeling of HIFU thermal therapies. 

PMID- 24077027
TI  - Sensitive capture of circulating tumour cells by functionalized graphene oxide
      nanosheets.
AB  - The spread of cancer throughout the body is driven by circulating tumour cells
      (CTCs). These cells detach from the primary tumour and move from the bloodstream
      to a new site of subsequent tumour growth. They also carry information about the
      primary tumour and have the potential to be valuable biomarkers for disease
      diagnosis and progression, and for the molecular characterization of certain
      biological properties of the tumour. However, the limited sensitivity and
      specificity of current methods for measuring and studying these cells in patient
      blood samples prevents the realization of their full clinical potential. The use
      of microfluidic devices is a promising method for isolating CTCs. However, the
      devices are reliant on three-dimensional structures, which limits further
      characterization and expansion of cells on the chip. Here we demonstrate an
      effective approach to isolating CTCs from blood samples of pancreatic, breast and
      lung cancer patients, by using functionalized graphene oxide nanosheets on a
      patterned gold surface. CTCs were captured with high sensitivity at a low
      concentration of target cells (73 +/- 32.4% at 3-5 cells per ml blood).

PMID- 24077028
TI  - Self-assembly of carbon nanotubes and antibodies on tumours for targeted
      amplified delivery.
AB  - Single-walled carbon nanotubes (SWNTs) can deliver imaging agents or drugs to
      tumours and offer significant advantages over approaches based on antibodies or
      other nanomaterials. In particular, the nanotubes can carry a substantial amount
      of cargo (100 times more than a monoclonal antibody), but can still be rapidly
      eliminated from the circulation by renal filtration, like a small molecule, due
      to their high aspect ratio. Here we show that SWNTs can target tumours in a two
      step approach in which nanotubes modified with morpholino oligonucleotide
      sequences bind to cancer cells that have been pretargeted with antibodies
      modified with oligonucleotide strands complementary to those on the nanotubes.
      The nanotubes can carry fluorophores or radioisotopes, and are shown to
      selectively bind to cancer cells in vitro and in tumour-bearing xenografted mice.
      The binding process is also found to lead to antigen capping and internalization
      of the antibody-nanotube complexes. The nanotube conjugates were labelled with
      both alpha-particle and gamma-ray emitting isotopes, at high specific activities.
      Conjugates labelled with alpha-particle-generating (225)Ac were found to clear
      rapidly, thus mitigating radioisotope toxicity, and were shown to be
      therapeutically effective in vivo. 

PMID- 24077029
TI  - Programmable chemical controllers made from DNA.
AB  - Biological organisms use complex molecular networks to navigate their environment
      and regulate their internal state. The development of synthetic systems with
      similar capabilities could lead to applications such as smart therapeutics or
      fabrication methods based on self-organization. To achieve this, molecular
      control circuits need to be engineered to perform integrated sensing, computation
      and actuation. Here we report a DNA-based technology for implementing the
      computational core of such controllers. We use the formalism of chemical reaction
      networks as a 'programming language' and our DNA architecture can, in principle,
      implement any behaviour that can be mathematically expressed as such. Unlike
      logic circuits, our formulation naturally allows complex signal processing of
      intrinsically analogue biological and chemical inputs. Controller components can
      be derived from biologically synthesized (plasmid) DNA, which reduces errors
      associated with chemically synthesized DNA. We implement several building-block
      reaction types and then combine them into a network that realizes, at the
      molecular level, an algorithm used in distributed control systems for achieving
      consensus between multiple agents. 

PMID- 24077030
TI  - Switching of ferroelectric polarization in epitaxial BaTiO3 films on silicon
      without a conducting bottom electrode.
AB  - Epitaxial growth of SrTiO3 on silicon by molecular beam epitaxy has opened up the
      route to the integration of functional complex oxides on a silicon platform.
      Chief among them is ferroelectric functionality using perovskite oxides such as
      BaTiO3. However, it has remained a challenge to achieve ferroelectricity in
      epitaxial BaTiO3 films with a polarization pointing perpendicular to the silicon
      substrate without a conducting bottom electrode. Here, we demonstrate
      ferroelectricity in such stacks. Synchrotron X-ray diffraction and high
      resolution scanning transmission electron microscopy reveal the presence of
      crystalline domains with the long axis of the tetragonal structure oriented
      perpendicular to the substrate. Using piezoforce microscopy, polar domains can be
      written and read and are reversibly switched with a phase change of 180 degrees .
      Open, saturated hysteresis loops are recorded. Thus, ferroelectric switching of 8
      to 40-nm-thick BaTiO3 films in metal-ferroelectric-semiconductor structures is
      realized, and field-effect devices using this epitaxial oxide stack can be
      envisaged.

PMID- 24077031
TI  - The effect of the polymorphisms of 5-HTTLPR on new onset of depression in
      patients who underwent pacemaker implantation.
AB  - AIM: To study the role of serotonin transporter gene (5-HTTLPR) polymorphisms in
      the incidence of depression in a Chinese cohort who underwent pacemaker (PM)
      implantation. METHODS: A total of 294 patients treated with PMs were enrolled.
      The 5-HTTLPR gene polymorphism was determined. RESULTS: We found that the 5
      HTTLPR SS genotype was significantly associated with the risk of depression after
      PM implantation (odds ratio=3.916, compared with LL carriers, P<0.001),
      especially in female patients and patients who are smokers. Female SS genotype
      carries 9.75 times higher risk for depression, and smokers with the SS genotype
      had 9.45 times higher risk for new onset of depression after the procedure. Pace
      mode had no influence on the onset of depression. CONCLUSION: This study suggests
      a significant association between the 5-HTTLPR gene polymorphism and the new
      onset of depression after PM implantation, especially in women or those who were
      smokers.

PMID- 24077032
TI  - Time-course of attention biases in social phobia.
AB  - Theoretical models of social phobia implicate preferential attention to social
      threat in the maintenance of anxiety symptoms, though there has been limited work
      characterizing the nature of these biases over time. The current study utilized
      eye-movement data to examine the time-course of visual attention over 1500ms
      trials of a probe detection task. Nineteen participants with a primary diagnosis
      of social phobia based on DSM-IV criteria and 20 non-clinical controls completed
      this task with angry, fearful, and happy face trials. Overt visual attention to
      the emotional and neutral faces was measured in 50ms segments across the trial.
      Over time, participants with social phobia attend less to emotional faces and
      specifically less to happy faces compared to controls. Further, attention to
      emotional relative to neutral expressions did not vary notably by emotion for
      participants with social phobia, but control participants showed a pattern after
      1000ms in which over time they preferentially attended to happy expressions and
      avoided negative expressions. Findings highlight the importance of considering
      attention biases to positive stimuli as well as the pattern of attention between
      groups. These results suggest that attention "bias" in social phobia may be
      driven by a relative lack of the biases seen in non-anxious participants. 

PMID- 24077034
TI  - CD8+ T cell recognition of epitopes within the capsid of adeno-associated virus 8
      based gene transfer vectors depends on vectors' genome.
AB  - Self-complementary adeno-associated viral (AAV) vectors expressing human factor
      IX (hF.IX) have achieved transient or sustained correction of hemophilia B in
      human volunteers. High doses of AAV2 or AAV8 vectors delivered to the liver
      caused in several patients an increase in transaminases accompanied by a rise in
      AAV capsid-specific T cells and a decrease in circulating hF.IX levels suggesting
      immune-mediated destruction of vector-transduced cells. Kinetics of these adverse
      events differed in patients receiving AAV2 or AAV8 vectors causing rise in
      transaminases at 3 versus 8 weeks after vector injection, respectively. To test
      if CD8+ T cells to AAV8 vectors, which are similar to AAV2 vectors are fully
      gutted vectors and thereby fail to encode structural viral proteins, could cause
      damage at this late time point, we tested in a series of mouse studies how long
      major histocompatibility (MHC) class I epitopes within AAV8 capsid can be
      presented to CD8+ T cells. Our results clearly show that depending on the
      vectors' genome, CD8+ T cells can detect such epitopes on AAV8's capsid for up to
      6 months indicating that the capsid of AAV8 degrades slowly in mice.

PMID- 24077033
TI  - Association of CRHR1 variants and posttraumatic stress symptoms in hurricane
      exposed adults.
AB  - Posttraumatic stress disorder (PTSD) is a moderately heritable anxiety disorder
      that may develop after exposure to trauma. However, only few genetic variants
      that relate to PTSD have been studied. This study examined the relationship
      between 12 single nucleotide polymorphisms (SNPs) in the corticotropin-releasing
      hormone receptor 1 gene (CRHR1) and post-disaster PTSD symptoms and diagnosis in
      adults exposed to 2004 Florida hurricanes. CRHR1 regulates the hypothalamic
      pituitary-adrenal (HPA) axis; dysregulation of the HPA axis is characteristic of
      stress phenotypes. Final analyses were conducted in the European-American (EA)
      subsample (n=564) due to population stratification. After correction for multiple
      testing, rs12938031 and rs4792887 remained associated with post-hurricane PTSD
      symptoms. Additionally, rs12938031 was associated with post-hurricane diagnosis
      of PTSD. This study is the first to examine CRHR1 in relation to PTSD in adults,
      and provides evidence for the importance of CRHR1 variation in the etiology of
      PTSD. Although results are preliminary and require replication, they justify
      follow-up efforts to characterize how this gene relates to PTSD. 

PMID- 24077037
TI  - Antone (Tony) L. Brooks: a life in science during the first three-quarters of a
      century of the atomic age.

PMID- 24077035
TI  - [Advanced directives: nurses' and physicians' representations in 2012].
AB  - In cancer patients, decision-making process is crucial and patient's involvement
      is described as a central component. In 2005, a new tool appears to convey
      patient's opinion even if he is not able to communicate anymore: advanced
      directives (AD). Unfortunately, their documentation is marginal. The objective of
      this study was to investigate nurses' and physicians' representations towards AD.
      A questionnaire had been sent to hospitals, public health facilities and liberal
      practitioners during February 2012. We collected responses from 42/251 physicians
      (17 %) and 80/198 nurses (40 %). Sixty percent of participants reported that they
      were not familiar with the legislative framework for AD. For physicians, main
      barriers were patient cognitive impairment (P = 0.004) and lack of information on
      the clinical situation (P = 0.004). For nurses, difficulties were toward end of
      life and prognosis discussion (P = 0.002), clinical situation evolution since AD
      documentation (P = 0.008), time frame for AD application (P < 0.001) and the fact
      that final decision is made by physician alone (P = 0.015). AD should be part of
      a good medical practice and literature has highlighted the benefit of AD on
      patient's quality of life. End of life discussion therefore requires dedicated
      time and specific training for physicians and nurses to improve the rate of
      patients with AD.

PMID- 24077038
TI  - Thirty-sixth Lauriston S. Taylor Lecture on radiation protection and measurements
      -from the field to the laboratory and back: the what ifs, wows, and who cares of
      radiation biology.
AB  - My scientific journey started at the University of Utah chasing fallout. It was
      on everything, in everything, and was distributed throughout the ecosystem. This
      resulted in radiation doses to humans and caused me great concern. From this
      concern I asked the question, "Are there health effects from these radiation
      doses and levels of radioactive contamination?" I have invested my scientific
      career trying to address this basic question. While conducting research, I got
      acquainted with many of the What ifs of radiation biology. The major What if in
      my research was, "What if we have underestimated the radiation risk for
      internally-deposited radioactive material?" While conducting research to address
      this important question, many other What ifs came up related to dose, dose rate,
      and dose distribution. I also encountered a large number of Wows. One of the
      first was when I went from conducting environmental fallout studies to research
      in a controlled laboratory. The activity in fallout was expressed as pCi L-1,
      whereas it was necessary to inject laboratory animals with MUCi g-1 body weight
      to induce measurable biological changes, chromosome aberrations, and cancer. Wow!
      That is seven to nine orders of magnitude above the activity levels found in the
      environment. Other Wows have made it necessary for the field of radiation biology
      to make important paradigm shifts. For example, one shift involved changing from
      "hit theory" to total tissue responses as the result of bystander effects.
      Finally, Who cares? While working at U.S. Department of Energy headquarters and
      serving on many scientific committees, I found that science does not drive
      regulatory and funding decisions. Public perception and politics seem to be major
      driving forces. If scientific data suggested that risk had been underestimated,
      everyone cared. When science suggested that risk had been overestimated, no one
      cared. This result-dependent Who cares? was demonstrated as we tried to generate
      interactions by holding meetings with individuals involved in basic low-dose
      research, regulators, and the news media. As the scientists presented their
      "exciting data" that suggested that risk was overestimated, many of the
      regulators simply said, "We cannot use such data." The newspaper people said, "It
      is not possible to get such information by my editors." In spite of these
      difficulties, research results from basic science must be made available and
      considered by members of the public as well as by those that make regulatory
      recommendations. Public outreach of the data is critical and must continue to be
      a future focus to address properly the question of, "Who cares?" My journey in
      science, like many of yours, has been a mixture of chasing money, beatings, and
      the joys of unique and interesting research results. Perhaps through our
      experiences, we can improve research environments, funding, and use of the
      valuable information that is generated. Scientists that study at all levels of
      biological organization, from the environment to the laboratory and human
      epidemiology, must share expertise and data to address the What Ifs, Wows, and
      Who Cares of radiation biology.

PMID- 24077040
TI  - Ninth Annual Warren K. Sinclair Keynote Address: effects of childhood radiation
      exposure: an issue from computed tomography scans to Fukushima.
AB  - The acute and chronic effects of radiation on children have been and will
      continue to be of great social, public health, scientific, and clinical
      importance. The focus of interest on ionizing radiation and children has been
      clear for over half a century and ranges from the effects of fallout from nuclear
      weapons testing to exposures from accidents, natural radiation, and medical
      procedures. There is a loosely stated notion that "children are three to five
      times more sensitive to radiation than adults." Is this really true? In fact,
      children are at greater risk for some health effects, but not all. For a few
      sequelae, children may be more resistant than adults. Which are those effects?
      How and why do they occur? While there are clear instances of increased risk of
      some radiation-induced tumors in children compared to adults, there are other
      tumor types in which there appears to be little or no difference in risk by age
      at exposure and some in which published models that assume the same relative
      increase in risks for child compared to adult exposures apply to nearly all tumor
      types are not supported by the scientific data. The United Nations Scientific
      Committee on Effects of Atomic Radiation (UNSCEAR) has a task group producing a
      comprehensive report on the subject. The factors to be considered include
      relevant radiation sources; developmental anatomy and physiology; dosimetry; and
      stochastic, deterministic, and hereditary effects. 

PMID- 24077041
TI  - Radiological protection of the patient: an integral part of quality of care.
AB  - Modern medicine now demands rapid diagnosis and treatment often centered on
      multiple investigations using ionizing radiation, particularly computed
      tomography (CT). Technological development continues at a rapid pace, and there
      is also an inexorable rise in minimally invasive therapy using fluoroscopically
      guided techniques. This has offered great benefit to many patients, who otherwise
      may not be fit enough for more invasive surgery. However, there are now many
      younger patients being treated using such techniques, where the risks of
      radiation in the longer term become more of an issue. 

PMID- 24077043
TI  - Efforts to optimize radiation protection in interventional fluoroscopy.
AB  - While it has been known for more than a century that radiation presents risks to
      both the physician and the patient, skin injuries from fluoroscopy became
      increasingly rare after the 1930s, and radiation risk from fluoroscopy appeared
      to be adequately controlled. However, beginning in approximately 1975, new
      technologies and materials for interventional devices were developed. These
      enabled new procedures, and as these were instituted, skin injuries again
      occurred in patients. Four central issues were identified: equipment, quality
      management, operator training, and occupational radiation protection. Recognition
      that these were areas for improvement provoked changes in technology and practice
      that continue today. 

PMID- 24077044
TI  - Standardization versus individualization: how each contributes to managing dose
      in computed tomography.
AB  - Dose management in medical imaging is about using the right dose for the specific
      patient and the specific diagnostic task; since patients and diagnostic tasks
      vary widely, the applied doses must also vary widely. Thus, a large amount of the
      variation observed in the computed tomography (CT) doses applied in medical
      imaging is appropriate. However, unacceptable sources of variations also exist.
      For similar sized patients and similar diagnostic tasks, variations in the
      applied doses should be small. It is the responsibility of the medical
      professionals in the imaging community, therefore, to ensure appropriate
      variations while minimizing unacceptable variations. That is, imaging
      professionals must make it standard practice to optimize scan parameters in a way
      that is specific to both patient size and diagnostic task. 

PMID- 24077046
TI  - The Fukushima Dai-ichi accident: additional lessons from a radiological emergency
      assistance mission.
AB  - In response to the March 2011 earthquake-tsunami disaster and the Fukushima Dai
      ichi nuclear accident, a special nongovernmental Radiological Emergency
      Assistance Mission flew to Japan from the United States. Invited by one of
      Japan's largest hospital and healthcare groups and facilitated by a New York
      based international disaster relief organization, the mission included an
      emergency physician, a health physicist, and a disaster management specialist.
      During the 10 d mission, team members conducted fieldwork in areas affected by
      the earthquake, tsunami, and nuclear accident; went to cities and towns in the 20
      30 km Emergency Evacuation Preparation Zone around the damaged nuclear plant;
      visited other communities affected by the nuclear accident; went to evacuation
      shelters; met with mayors and other local officials; met with central government
      officials; exchanged observations, experiences, and information with Japanese
      medical, emergency response, and disaster management colleagues; and provided
      radiological information and training to more than 1,100 Japanese hospital and
      healthcare personnel and first responders. The mission produced many insights
      with potential relevance for radiological/nuclear emergency preparedness and
      response. The first "lessons learned" were published in December 2011. Since that
      time, additional broad insights from the mission and mission followup have been
      identified. Five of these new lessons, which focus primarily on community impacts
      and responses and public communication issues, are presented and discussed in
      this article. 

PMID- 24077047
TI  - Rad Resilient City: a preparedness checklist to save lives following a nuclear
      detonation.
AB  - The Rad Resilient City Checklist is a local planning tool that can help save tens
      of thousands of lives following a nuclear detonation. If prevention of nuclear
      terrorism fails, then reducing exposure to radioactive fallout is the
      intervention that can save the most lives following a nuclear detonation. Yet,
      most Americans are not familiar with correct safety measures against fallout, and
      many believe that nothing can be done to reduce the suffering and death inflicted
      by a nuclear attack. Moreover, cities have no checklist on how to prepare the
      emergency management infrastructure and the larger population for this hazard,
      despite hundreds of pages of useful guidance from the federal government and
      radiation professional organizations. The Rad Resilient City Checklist reverses
      this situation by converting the latest federal guidance and technical reports
      into clear, actionable steps for communities to take to protect their residents
      from exposure to radioactive fallout. The checklist reflects the shared judgment
      of the Nuclear Resilience Expert Advisory Group, a national panel led by the
      Center for Biosecurity and comprised of government decision makers, scientific
      experts, emergency responders, and leaders from business, volunteer, and
      community sectors. 

PMID- 24077049
TI  - Reference levels in the context of Fukushima and related lessons learned.
AB  - About 1 mo after the Fukushima Dai-ichi nuclear power plant accident, which was
      caused by the Great East Japan earthquake and tsunami on 11 March 2011, Japanese
      authorities set a dose criterion for the use of school playgrounds in Fukushima
      at 20 mSv y-1 based on the International Commission on Radiological Protection
      recommendation for the reference level for the public under the existing exposure
      situation. This dose criterion was intended as a start line for reducing the dose
      to children; however, it caused much confusion among the public due to the
      misunderstanding of the concept of optimization and the application of reference
      level. Also, concerns were caused by the lack of precise but understandable
      information on radiation effects. This situation highlighted the importance of an
      understanding of radiation protection concepts by members of the general public
      and the outreach activities of radiation protection experts, both of which are
      essential for Fukushima recovery.

PMID- 24077053
TI  - Effect of interactions with the chaperonin cavity on protein folding and
      misfolding.
AB  - Recent experimental and computational results have suggested that attractive
      interactions between a chaperonin and an enclosed substrate can have an important
      effect on the protein folding rate: it appears that folding may even be slower
      inside the cavity than under unconfined conditions, in contrast to what we would
      expect from excluded volume effects on the unfolded state. Here we examine
      systematically the dependence of the protein stability and folding rate on the
      strength of such attractive interactions between the chaperonin and substrate, by
      using molecular simulations of model protein systems in an idealised attractive
      cavity. Interestingly, we find a maximum in stability, and a rate which indeed
      slows down at high attraction strengths. We have developed a simple
      phenomenological model which can explain the variations in folding rate and
      stability due to differing effects on the free energies of the unfolded state,
      folded state, and transition state; changes in the diffusion coefficient along
      the folding coordinate are relatively small, at least for our simplified model.
      In order to investigate a possible role for these attractive interactions in
      folding, we have studied a recently developed model for misfolding in multidomain
      proteins. We find that, while encapsulation in repulsive cavities greatly
      increases the fraction of misfolded protein, sufficiently strong attractive
      protein-cavity interactions can strongly reduce the fraction of proteins reaching
      misfolded traps. 

PMID- 24077054
TI  - Environmental factors acting during development to influence MS risk: insights
      from animal studies.
AB  - Multiple sclerosis (MS) is an autoimmune demyelinating disease of the central
      nervous system with an increasing incidence in females. Epidemiological data
      strongly implicate environmental factors acting at the population level during
      gestation, childhood and adulthood in the increasing incidence of MS. Several
      such factors are implicated in disease risk, but their causality remains
      unproven, while other factors remain unknown. An understanding of the risk
      factors acting during development is particularly limited. Animal studies could
      potentially bridge the gap between observational epidemiology and clinical
      intervention, providing not only direct evidence of causality for a given
      environmental agent, but also an opportunity to dissect the underlying molecular
      mechanisms. Given a rodent's short gestational and developmental period, the
      effects of developmental exposure can also be readily addressed. Nonetheless,
      studies in this area so far are few. In this review, we summarize the insights
      gleaned from studies that test environmental influences in animal models of MS,
      with a particular focus on gestational and early life exposures. 

PMID- 24077055
TI  - Contact investigation for active tuberculosis among child contacts in Uganda.
AB  - BACKGROUND: Tuberculosis is a large source of morbidity and mortality among
      children. However, limited studies characterize childhood tuberculosis disease,
      and contact investigation is rarely implemented in high-burden settings. In one
      of the largest pediatric tuberculosis contact investigation studies in a resource
      limited setting, we assessed the yield of contact tracing on childhood
      tuberculosis and indicators for disease progression in Uganda. METHODS: Child
      contacts aged <15 years in Kampala, Uganda, were enrolled from July 2002 to June
      2009 and evaluated for tuberculosis disease via clinical, radiographic, and
      laboratory methods for up to 24 months. RESULTS: Seven hundred sixty-one child
      contacts were included in the analysis. Prevalence of tuberculosis in our child
      population was 10%, of which 71% were culture-confirmed positive. There were no
      cases of disseminated tuberculosis, and 483 of 490 children (99%) started on
      isoniazid preventative therapy did not develop disease. Multivariable testing
      suggested risk factors including human immunodeficiency virus (HIV) status (odds
      ratio [OR], 7.90; P < .001), and baseline positive tuberculin skin test (OR,
      2.21; P = .03); BCG vaccination was particularly protective, especially among
      children aged <=5 years (OR, 0.23; P < .001). Adult index characteristics such as
      sex, HIV status, and extent or severity of disease were not associated with
      childhood disease. CONCLUSIONS: Contact tracing for children in high-burden
      settings is able to identify a large percentage of culture-confirmed positive
      tuberculosis cases before dissemination of disease, while suggesting factors for
      disease progression to identify who may benefit from targeted screening.

PMID- 24077056
TI  - Editorial commentary: more evidence to support screening of child contacts of
      tuberculosis cases: if not now, then when?

PMID- 24077057
TI  - Interaction between the transcriptional corepressor Sin3B and voltage-gated
      sodium channels modulates functional channel expression.
AB  - Proteins that interact with voltage-gated sodium (Na(v)) channels are important
      in channel sorting and modulation. In this study, we identified the
      transcriptional regulator, Sin3B, as a novel binding partner of Na(v) channels in
      a yeast two-hybrid screen and confirmed the interaction using pull-down assays,
      co-immunoprecipitation, and immunofluorescence-colocalization. Because both long
      (~1100-residue) and short (N-terminal 293 residues) Sin3B variants interacted
      with Na(v) channels, binding occurred within the N-terminal region containing two
      paired-amphipathic helix domains. In Na(v) channels, Sin3B bound to a 132-residue
      portion of the cytoplasmic C-terminus. Expression of the short Sin3B variant
      strongly reduced native sodium current and Na(v)-channel gating charge in the
      neuronal cell line N1E-115, without affecting the voltage-dependence of
      activation. Because the total amount of channel protein was unchanged by Sin3B,
      binding of Sin3B likely decreases the number of channels in the plasma membrane,
      suggesting that interaction with Sin3B influences Na(v)-channel trafficking or
      stability in the membrane.

PMID- 24077058
TI  - Combination of myocardial perfusion imaging and SYNTAX Score. A more rational
      approach to revascularization.

PMID- 24077059
TI  - Linoleic acid. A novel mechanism of endothelial cell dysfunction.

PMID- 24077060
TI  - Impact of physical activity on cardiovascular events in patients with chronic
      heart failure. A multicenter prospective cohort study.
AB  - BACKGROUND: We have previously demonstrated that the prevalence of metabolic
      syndrome in chronic heart failure (CHF) is more than double compared with the
      general population in Japan. However, the impact of physical activity on
      cardiovascular events in CHF patients remains to be fully elucidated. METHODS AND
      RESULTS: We performed a prospective, nationwide large-scale multicenter study of
      9,178 patients with stage A/B/C/D CHF in Japan. We obtained the baseline physical
      activity data for 7,292 and yearly changes in physical activity data during a 3
      year follow-up period for 4,353 patients. We divided the patients into high- and
      low-exercise groups by using the median value of physical activity in the stage
      A/B and C/D groups. In both groups, patients who exercised more were
      characterized by younger age and less advanced stage of CHF. Importantly, the
      baseline physical activity levels were significantly associated with all-cause
      death, heart failure (HF) hospitalization and other cardiovascular events (except
      acute myocardial infarction, stroke, HF hospitalization). Furthermore, the yearly
      change in physical activity level was also significantly associated with HF
      hospitalization and other cardiovascular events in both groups. CONCLUSIONS: The
      baseline level of physical activity and its yearly changes are significantly
      associated with all-cause death and major cardiovascular events in both stage A/B
      and C/D patients, suggesting that physical activity could be an important
      therapeutic target to improve the long-term prognosis of CHF patients.

PMID- 24077061
TI  - Ultrafine particle concentrations in the surroundings of an urban area: comparing
      downwind to upwind conditions using Generalized Additive Models (GAMs).
AB  - The aim of this study was to investigate the influence of an urban area on
      ultrafine particle (UFP) concentration in nearby surrounding areas. We assessed
      how downwind and upwind conditions affect the UFP concentration at a site placed
      a few kilometres from the city border. Secondarily, we investigated the
      relationship among other meteorological factors, temporal variables and UFP. Data
      were collected for 44 days during 2008 and 2009 at a rural site placed about 3
      kilometres from Bologna, in northern Italy. Measurements were performed using a
      spectrometer (FMPS TSI 3091). The average UFP number concentration was 11 776 (+/
      7836) particles per cm(3). We analysed the effect of wind direction in a
      multivariate Generalized Additive Model (GAM) adjusted for the principal
      meteorological parameters and temporal trends. An increase of about 25% in UFP
      levels was observed when the site was downwind of the urban area, compared with
      the levels observed when wind blew from rural areas. The size distribution of
      particles was also affected by the wind direction, showing higher concentration
      of small size particles when the wind blew from the urban area. The GAM showed a
      good fit to the data (R(2) = 0.81). Model choice was via Akaike Information
      Criteria (AIC). The analysis also revealed that an approach based on
      meteorological data plus temporal trends improved the goodness of the fit of the
      model. In addition, the findings contribute to evidence on effects of exposure to
      ultrafine particles on a population living in city surroundings. 

PMID- 24077063
TI  - Accelerating free breathing myocardial perfusion MRI using multi coil radial k-t
      SLR.
AB  - The clinical utility of myocardial perfusion MR imaging (MPI) is often restricted
      by the inability of current acquisition schemes to simultaneously achieve high
      spatio-temporal resolution, good volume coverage, and high signal to noise ratio.
      Moreover, many subjects often find it difficult to hold their breath for
      sufficiently long durations making it difficult to obtain reliable MPI data.
      Accelerated acquisition of free breathing MPI data can overcome some of these
      challenges. Recently, an algorithm termed as k - t SLR has been proposed to
      accelerate dynamic MRI by exploiting sparsity and low rank properties of dynamic
      MRI data. The main focus of this paper is to further improve k - t SLR and
      demonstrate its utility in considerably accelerating free breathing MPI. We
      extend its previous implementation to account for multi-coil radial MPI
      acquisitions. We perform k - t sampling experiments to compare different radial
      trajectories and determine the best sampling pattern. We also introduce a novel
      augmented Lagrangian framework to considerably improve the algorithm's
      convergence rate. The proposed algorithm is validated using free breathing rest
      and stress radial perfusion data sets from two normal subjects and one patient
      with ischemia. k - t SLR was observed to provide faithful reconstructions at high
      acceleration levels with minimal artifacts compared to existing MPI acceleration
      schemes such as spatio-temporal constrained reconstruction and k - t
      SPARSE/SENSE. 

PMID- 24077064
TI  - Cerebellar morphology and the effects of stimulant medications in youths with
      attention deficit-hyperactivity disorder.
AB  - The cerebellum is emerging as a key anatomical structure underlying normal
      attentional and cognitive control mechanisms. Dysregulation within cerebellar
      circuits may contribute to the core symptoms of Attention Deficit/Hyperactivity
      Disorder (ADHD). In the present study we aimed to characterize surface
      morphological features of the cerebellum in ADHD and healthy comparison youths.
      Further, we studied the association of cerebellar morphology with the severity of
      ADHD symptoms and the effects of stimulant treatment. We examined 46 youths with
      ADHD and 59 comparison youths 8-18 years of age in a cross-sectional, case
      control study using magnetic resonance imaging. Measures of cerebellar surface
      morphology were the primary outcome. Relative to comparison participants, youths
      with ADHD exhibited smaller regional volumes corresponding to the lateral surface
      of the left anterior and the right posterior cerebellar hemispheres. Stimulant
      medication was associated with larger regional volumes over the left cerebellar
      surface, whereas more severe ADHD symptoms were associated with smaller regional
      volumes in the vermis. We used optimized measures of morphology to detect
      alterations in cerebellar anatomy specific to ADHD, dimensions of symptomology,
      and stimulant treatment. Duration of treatment correlated positively with volumes
      of specific cerebellar subregions, supporting a model whereby compensatory
      morphological changes support the effects of stimulant treatment. 

PMID- 24077065
TI  - Hippocampal and amygdalar volumetric differences in pathological gambling: a
      preliminary study of the associations with the behavioral inhibition system.
AB  - The behavioral inhibition system (BIS) and behavioral activation system (BAS) are
      hypothesized to underlie motivated behavior, relate to hippocampal and amygdalar
      function, and link to pathological gambling (PG). Prior studies have not
      investigated hippocampal and amygdalar volumes in PG and their relationships to
      BIS/BAS measures. Structural MRI scans and BIS/BAS and other clinical measures
      were obtained from 32 PG individuals and 47 healthy comparison (HC) individuals.
      Volumetric measures of the hippocampus and amygdala were assessed using
      FreeSurfer and related to BIS/BAS measures. PG relative to HC individuals
      demonstrated diminished volume in the left hippocampus and right amygdala and
      higher BIS and BAS scores. BIS scores were positively correlated with left
      hippocampal and left amygdalar volumes in PG individuals. The findings of
      relatively diminished hippocampal and amygdalar volumes in PG individuals
      resonate with findings from substance-dependent groups. Relationships between
      amygdalar and hippocampal volumes and BIS measures in PG suggest that individual
      differences in these structures may contribute to avoidance behaviors in PG. 

PMID- 24077066
TI  - Neurosteroid Agonist at GABAA receptor induces persistent neuroplasticity in VTA
      dopamine neurons.
AB  - The main fast-acting inhibitory receptors in the mammalian brain are gamma
      aminobutyric acid type-A (GABAA) receptors for which neurosteroids, a subclass of
      steroids synthesized de novo in the brain, constitute a group of endogenous
      ligands with the most potent positive modulatory actions known. Neurosteroids can
      act on all subtypes of GABAA receptors, with a preference for delta-subunit
      containing receptors that mediate extrasynaptic tonic inhibition. Pathological
      conditions characterized by emotional and motivational disturbances are often
      associated with perturbation in the levels of endogenous neurosteroids. We
      studied the effects of ganaxolone (GAN)-a synthetic analog of endogenous
      allopregnanolone that lacks activity on nuclear steroid receptors-on the
      mesolimbic dopamine (DA) system involved in emotions and motivation. A single
      dose of GAN in young mice induced a dose-dependent, long-lasting neuroplasticity
      of glutamate synapses of DA neurons ex vivo in the ventral tegmental area (VTA).
      Increased alpha-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid (AMPA)/N
      methyl-D-aspartate ratio and rectification of AMPA receptor responses even at 6
      days after GAN administration suggested persistent synaptic targeting of GluA2
      lacking AMPA receptors. This glutamate neuroplasticity was not observed in GABAA
      receptor delta-subunit-knockout (delta-KO) mice. GAN (500 nM) applied locally to
      VTA selectively increased tonic inhibition of GABA interneurons and triggered
      potentiation of DA neurons within 4 h in vitro. Place-conditioning experiments in
      adult wild-type C57BL/6J and delta-KO mice revealed aversive properties of
      repeated GAN administration that were dependent on the delta-subunits. Prolonged
      neuroadaptation to neurosteroids in the VTA might contribute to both the
      physiology and pathophysiology underlying processes and changes in motivation,
      mood, cognition, and drug addiction. 

PMID- 24077067
TI  - Monkeys that voluntarily and chronically drink alcohol damage their brains: a
      longitudinal MRI study.
AB  - Neuroimaging has consistently documented reductions in the brain tissue of
      alcoholics. Inability to control comorbidity, environmental insult, and
      nutritional deficiency, however, confound the ability to assess whether ethanol
      itself is neurotoxic. Here we report monkey oral ethanol self-administration
      combined with MR imaging to characterize brain changes over 15 months in 18 well
      nourished rhesus macaques. Significant brain volume shrinkage occurred in the
      cerebral cortices of monkeys drinking >= 3 g/kg ethanol/day (12 alcoholic drinks)
      at 6 months, and this persisted throughout the period of continuous access to
      ethanol. Correlation analyses revealed a cerebral cortical volumetric loss of
      ~0.11% of the intracranial vault for each daily drink (0.25 g/kg), and selective
      vulnerability of cortical and non-cortical brain regions. These results
      demonstrate for the first time a direct relation between oral ethanol intake and
      measures of decreased brain gray matter volume in vivo in primates. Notably,
      greater volume shrinkage occurred in monkeys with younger drinking onset that
      ultimately became heavier drinkers than monkeys with older drinking onset. The
      pattern of volumetric changes observed in nonhuman primates following 15 months
      of drinking suggests that cerebral cortical gray matter changes are the first
      macroscopic manifestation of chronic ethanol exposure in the brain.

PMID- 24077069
TI  - ADHD symptom prevalence and risk factors in a sample of toddlers with ASD or who
      are at risk for developmental delay.
AB  - Individuals with attention deficit/hyperactivity disorder (ADHD) experience
      difficulties with inattention, hyperactivity, and impulsivity which significantly
      interfere with their daily functioning. Symptoms of the disorder occur in
      children, but the developmental trajectory of ADHD symptoms is not known. The
      present study examines the prevalence of ADHD symptomology in a sample of 2956
      children who were determined to be at risk for developmental delay. Prevalence
      rates for ADHD in the overall sample was 4.50%, and prevalence rates by gender,
      race, and presence of autism spectrum disorder (ASD) were comparable. The
      prevalence was not significantly different in children with an ASD diagnosis. No
      significant effects of gender or ASD diagnosis were observed. ADHD should be
      considered as a diagnosis among young children who present to clinics for
      children at risk for developmental delay, and future researchers should further
      study its developmental trajectory, beginning at an early age. 

PMID- 24077068
TI  - Adolescents with a history of specific language impairment (SLI): strengths and
      difficulties in social, emotional and behavioral functioning.
AB  - Adolescents with specific language impairment (SLI) are at a greater risk of
      emotional and behavioral problems compared to their typically developing (TD)
      peers, but little is known about their self-perceived strengths and difficulties.
      In this study, the self-reported social, emotional and behavioral functioning of
      139 adolescents with a history of SLI and 124 TD individuals at age 16 was
      examined. The self-report version of the Strengths and Difficulties Questionnaire
      (SDQ) was used to assess their prosocial behavior and levels of peer, emotional
      and behavioral difficulties. Associations of these areas of functioning with
      gender, verbal and non-verbal skills were also investigated. Adolescents with a
      history of SLI were more likely than their TD peers to report higher levels of
      peer problems, emotional symptoms, hyperactivity and conduct problems. The
      majority of adolescents in both groups (87% SLI and 96% TD), however, reported
      prosocial behavior within the typical range. Difficulty with peer relations was
      the strongest differentiator between the groups, with the odds of reporting
      borderline or abnormally high levels of peer problems being 12 times higher for
      individuals with a history of SLI. Adolescents with poorer receptive language
      skills were also more likely to report higher levels of emotional and behavioral
      difficulties. The findings of this study identify likely traits that may lead to
      referral to services. 

PMID- 24077070
TI  - Development of a scale to measure fidelity to manualized group-based cognitive
      behavioural interventions for people with intellectual disabilities.
AB  - The context for the present study was a cluster-randomized controlled trial of a
      group-based anger-management intervention, delivered by day-service staff. We
      aimed to develop a scale to measure the fidelity of manualized cognitive
      behavioural therapy (CBT) delivered to adults with intellectual disabilities in
      group-based settings. A 30-item monitoring instrument (the MAnualized Group
      Intervention Check: MAGIC) was adapted from an existing fidelity-monitor
      instrument for individual CBT. Two sessions for 27 groups were observed by pairs
      of monitors who had no other contact with the intervention. 16 observers
      participated, in 15 unique pairings. Observers recorded high levels of inter
      rater reliability and the scale had good internal consistency. Fidelity ratings
      predicted two key outcomes of the intervention, and were themselves predicted by
      the therapists' clinical supervisors. 

PMID- 24077071
TI  - Health-related physical fitness children with severe and moderate developmental
      coordination disorder.
AB  - The present study aims to examine physical fitness among children with
      developmental coordination disorder (DCD) with varying degrees of severity
      (moderate and severe - mDCD, sDCD), and a group of children without DCD (wDCD),
      in the city of Manaus, Brazil. Initially, 180 children aged 6-10 years old
      participated in this study. After being diagnosed according to the DSM-IV-TR, 63
      children were then divided into three groups (21 in each group). Health-related
      physical fitness was measured by means of the Fitnessgram, which included several
      core components, namely, body composition, muscle strength and endurance,
      flexibility, and cardiorespiratory resistance. The results showed no
      statistically significant differences between both groups in any of the assessed
      components. However, when analyzing the results of each component according to
      the criteria of the Fitnessgram, we observed that, regardless of the
      classification group, less than half of the children achieved scores that,
      according to the motor tests, would classify them as having a healthy fitness.
      Children with sDCD, mDCD and wDCD presented similar levels of health-related
      physical fitness, with an unsatisfactory performance for the component strength
      and muscular endurance. We therefore emphasize the importance of further research
      in this area, more particularly when it comes to following the development of
      motor skills and physical fitness in children with DCD, as well as the
      observation of the interactions between these variables over time.

PMID- 24077072
TI  - Technology-aided programs to enable persons with multiple disabilities to choose
      among environmental stimuli using a smile or a tongue response.
AB  - Persons with multiple disabilities, including pervasive motor impairment, may
      have problems controlling even small responses (e.g., vocal emissions, finger
      movements, or prolonged eyelid closures) within time-sensitive situations, such
      as those involved in choice programs. Recent research has indicated that smile
      expressions can be used as functional choice responses for some of these persons.
      The present two studies were aimed at assessing the smile response for a child
      with congenital multiple disabilities and a tongue response for a post-coma man
      who had recovered his consciousness but presented with pervasive multiple
      disabilities. The first of the two studies represented a research extension
      (i.e., a new case with a slightly adapted microswitch technology) concerning the
      smile response, which had recently been evaluated with few other cases. The
      second study represented a new effort to assess the tongue response within a
      choice program and for a post-coma man with multiple disabilities. The results
      showed that the participants used the smile and the tongue responses successfully
      while they were apparently unsuccessful in using a slight head/chin movement
      response. Their choice behavior focused reliably on preferred stimuli and avoided
      non-preferred stimuli. Implications of the results are discussed. 

PMID- 24077073
TI  - In planta assessment of the role of thioredoxin h proteins in the regulation of S
      locus receptor kinase signaling in transgenic Arabidopsis.
AB  - The self-incompatibility (SI) response of the Brassicaceae is mediated by allele
      specific interaction between the stigma-localized S-locus receptor kinase (SRK)
      and its ligand, the pollen coat-localized S-locus cysteine-rich protein (SCR).
      Based on work in Brassica spp., the thioredoxin h-like proteins THL1 and THL2,
      which interact with SRK, have been proposed to function as oxidoreductases that
      negatively regulate SRK catalytic activity. By preventing the spontaneous
      activation of SRK in the absence of SCR ligand, these thioredoxins are thought to
      be essential for the success of cross pollinations in self-incompatible plants.
      However, the in planta role of thioredoxins in the regulation of SI signaling has
      not been conclusively demonstrated. Here, we addressed this issue using
      Arabidopsis thaliana plants transformed with the SRKb-SCRb gene pair isolated
      from self-incompatible Arabidopsis lyrata. These plants express an intense SI
      response, allowing us to exploit the extensive tools and resources available in
      A. thaliana for analysis of SI signaling. To test the hypothesis that SRK is
      redox regulated by thioredoxin h, we expressed a mutant form of SRKb lacking a
      transmembrane-localized cysteine residue thought to be essential for the SRK
      thioredoxin h interaction. We also analyzed transfer DNA insertion mutants in the
      A. thaliana orthologs of THL1 and THL2. In neither case did we observe an effect
      on the pollination responses of SRKb-expressing stigmas toward incompatible or
      compatible pollen. Our results are consistent with the conclusion that, contrary
      to their proposed role, thioredoxin h proteins are not required to prevent the
      spontaneous activation of SRK in the A. thaliana stigma. 

PMID- 24077075
TI  - Question on long-lived impurities of yttrium-90 labeled microspheres.

PMID- 24077076
TI  - Response to DeCaire.

PMID- 24077074
TI  - Root transcript profiling of two Rorippa species reveals gene clusters associated
      with extreme submergence tolerance.
AB  - Complete submergence represses photosynthesis and aerobic respiration, causing
      rapid mortality in most terrestrial plants. However, some plants have evolved
      traits allowing them to survive prolonged flooding, such as species of the genus
      Rorippa, close relatives of Arabidopsis (Arabidopsis thaliana). We studied plant
      survival, changes in carbohydrate and metabolite concentrations, and
      transcriptome responses to submergence of two species, Rorippa sylvestris and
      Rorippa amphibia. We exploited the close relationship between Rorippa species and
      the model species Arabidopsis by using Arabidopsis GeneChip microarrays for whole
      genome transcript profiling of roots of young plants exposed to a 24-h
      submergence treatment or air. A probe mask was used based on hybridization of
      genomic DNA of both species to the arrays, so that weak probe signals due to
      Rorippa species/Arabidopsis mismatches were removed. Furthermore, we compared
      Rorippa species microarray results with those obtained for roots of submerged
      Arabidopsis plants. Both Rorippa species could tolerate deep submergence, with R.
      sylvestris surviving much longer than R. amphibia. Submergence resulted in the
      induction of genes involved in glycolysis and fermentation and the repression of
      many energy-consuming pathways, similar to the low-oxygen and submergence
      response of Arabidopsis and rice (Oryza sativa). The qualitative responses of
      both Rorippa species to submergence appeared roughly similar but differed
      quantitatively. Notably, glycolysis and fermentation genes and a gene encoding
      sucrose synthase were more strongly induced in the less tolerant R. amphibia than
      in R. sylvestris. A comparison with Arabidopsis microarray studies on submerged
      roots revealed some interesting differences and potential tolerance-related genes
      in Rorippa species. 

PMID- 24077077
TI  - RSO interview with Les Morrison.

PMID- 24077078
TI  - An improved method for calibrating the gantry angles of linear accelerators.
AB  - Linear particle accelerators (linacs) are widely used in radiotherapy procedures;
      therefore, accurate calibrations of gantry angles must be performed to prevent
      the exposure of healthy tissue to excessive radiation. One of the common methods
      for calibrating these angles is the spirit level method. In this study, a new
      technique for calibrating the gantry angle of a linear accelerator was examined.
      A cubic phantom was constructed of Styrofoam with small lead balls, embedded at
      specific locations in this foam block. Several x-ray images were taken of this
      phantom at various gantry angles using an electronic portal imaging device on the
      linac. The deviation of the gantry angles were determined by analyzing the images
      using a customized computer program written in ImageJ (National Institutes of
      Health). Gantry angles of 0, 90, 180, and 270 degrees were chosen and the results
      of both calibration methods were compared for each of these angles. The results
      revealed that the image method was more precise than the spirit level method. For
      the image method, the average of the measured values for the selected angles of
      0, 90, 180, and 270 degrees were found to be -0.086 +/- 0.011, 90.018 +/- 0.011,
      180.178 +/- 0.015, and 269.972 +/- 0.006 degrees, respectively. The corresponding
      average values using the spirit level method were 0.2 +/- 0.03, 90.2 +/- 0.04,
      180.1 +/- 0.01, and 269.9 +/- 0.05 degrees, respectively. Based on these
      findings, the new method was shown to be a reliable technique for calibrating the
      gantry angle.

PMID- 24077080
TI  - Analysis of exposure to electromagnetic fields in a healthcare environment:
      simulation and experimental study.
AB  - Recent advances in wireless technologies have lead to an increase in wireless
      instrumentation present in healthcare centers. This paper presents an analytical
      method for characterizing electric field (E-field) exposure within these
      environments. The E-field levels of the different wireless communications systems
      have been measured in two floors of the Canary University Hospital Consortium
      (CUHC). The electromagnetic (EM) conditions detected with the experimental
      measures have been estimated using the software EFC-400-Telecommunications (Narda
      Safety Test Solutions, Sandwiesenstrasse 7, 72793 Pfullingen, Germany). The
      experimental and simulated results are represented through 2D contour maps, and
      have been compared with the recommended safety and exposure thresholds. The
      maximum value obtained is much lower than the 3 V m(-1) that is established in
      the International Electrotechnical Commission Standard of Electromedical Devices.
      Results show a high correlation in terms of E-field cumulative distribution
      function (CDF) between the experimental and simulation results. In general, the
      CDFs of each pair of experimental and simulated samples follow a lognormal
      distribution with the same mean.

PMID- 24077079
TI  - Interceptor and Phantom Trials of EDNS at UPMC.
AB  - University of Pittsburgh Medical Center (UPMC) installed an Emergency Department
      Notification System (EDNS) in one of its hospitals. The system, manufactured by
      Thermo Fisher Scientific (Thermo Fisher Scientific, Inc., 81 Wyman Street,
      Waltham, MA 02454), consists of four NaI(Tl) scintillation detectors, a 2.5 L PVT
      gamma counter, a 512 channels multi-channel analyzer, a system controller, and a
      database-monitoring server. We evaluated a portable Interceptor InterceptorTM
      hand-held detector (Thermo Fisher Scientific, Inc., 81 Wyman Street, Waltham, MA
      02454) as part of the system for potential ambulancebased early detection and
      warning unit. We present the minimum detectable activity, distance, and isotope
      identification success rates along with the change in detector response to
      various radioisotope sources placed in a Rando(r) humanoid phantom. (The Phantom
      Laboratory. P.O. Box 511, Salem, NY 12865-0511 USA). The present paper reports
      these results.

PMID- 24077081
TI  - Experience in the management of disused lightning rods containing 241Am in a
      research institute in Brazil.
AB  - Radioactive lightning rods (RLR) were manufactured and installed in Brazil for
      almost two decades, before they were prohibited in 1989. Structures protected by
      this type of lightning preventers included residential buildings, schools,
      commercial and industrial facilities, among others. It is estimated that about
      3.4 TBq of 241Am were used by manufacturers, and a total of 75,000 pieces with a
      mean activity of about 46 MBq were in the market. While only a fraction of the
      total has been recovered, the almost twenty thousand pieces already collected at
      the Nuclear and Energy Research Institute (IPEN) had their sources successfully
      separated from the remaining recyclable metal scrap and are now encapsulated in
      lead containers for final disposal.

PMID- 24077082
TI  - Management of leaded PPE in the healthcare environment.
AB  - Management of a quality assurance program for leaded personal protective
      equipment (PPE) can be a challenge for large healthcare organizations. A program
      has been developed to effectively manage hundreds of pieces of leaded PPE at a
      large health system in North Carolina. Physical identification of pieces is
      accomplished using a combination of durable serialized labels for identification
      of individual pieces, and a color-coded tagging system for instant visual
      identification of inspection status. This process, coupled with maintaining
      routine quality assurance records using standard spreadsheet software, resulted
      in an effective leaded PPE management program with minimal capital overhead. 

PMID- 24077083
TI  - Using tablet technology in operational radiation safety applications.
AB  - Tablet computers have become a mainstream product in today's personal,
      educational, and business worlds. These tablets offer computing power, storage,
      and a wide range of available products to meet nearly every user need. To take
      advantage of this new computing technology, a system was developed for the Apple
      iPad (Apple Inc. 1 Infinite Loop Cupertino, CA 95014) to perform health and
      safety inspections in the field using editable PDFs and saving them to a database
      while keeping the process easy and paperless. 

PMID- 24077084
TI  - Role of 1-methyl-3-octylimidazolium chloride in the micellization behavior of
      amphiphilic drug amitriptyline hydrochloride.
AB  - The mixed micellization behaviour of amitriptyline hydrochloride (AMT) with ionic
      liquid (IL) 1-methyl-3-octylimidazolium hydrochloride, [C8mim][Cl], have been
      investigated using electrical conductivity, at different temperatures. The non
      ideal behaviour (i.e., synergistic interaction) of AMT-[C8mim][Cl] binary
      mixtures, explained by the deviations in critical micelle concentration (cmc)
      from ideal critical micelle concentration (cmc*) and micellar mole fraction
      (X(m)) from ideal micellar mole fraction (X(ideal)) values. The values of
      interaction parameter (beta) and activity coefficients (f1 and f2), also confirm
      the synergistic interaction. The excess free energy (DeltaGex) for the AMT
      [C8mim][Cl] binary mixtures explains, stability of mixed micelles in comparison
      to micelles of pure, AMT and [C8mim][Cl]. The calculated thermodynamic parameters
      (viz., the standard Gibbs energy change, DeltaGm(?), the standard enthalpy
      change, DeltaHm(?), the standard entropy change, DeltaSm(?)), suggest the
      dehydration of hydrophobic part of the drug at higher temperatures (>313K), not
      only in case of AMT but also in the presence of [C8mim][Cl]. 

PMID- 24077085
TI  - Influence of internal interfacial area on nanosecond relaxation of wheat gluten
      proteins as probed by broadband ultrasonic spectroscopy.
AB  - Understanding interactions between interfaces and biopolymers in complex
      industrially processed materials of plant origin will allow for their better
      utilization. Wheat flour doughs are one such material whose industrial use
      strongly depends on such interactions due to their effect on the mechanical
      properties of the dough. To date, mechanical characterizations of dough have been
      limited to a narrow range of frequencies. Here, ultrasonic spectroscopy
      measurements over a very broad frequency range are used to show that a fast
      volumetric relaxation occurs in dough; the nanosecond timescale of the relaxation
      is associated with ultrasonic stress-induced changes in the secondary structure
      of gluten proteins. Interestingly, there is a four-fold difference in the speed
      of this relaxation phenomenon in doughs mixed in air (where substantial internal
      interfacial area exists) compared to those mixed under vacuum (where bubbles are
      absent). Given the large internal interfacial area in dough, the amphiphilic
      proteins residing at gas bubble interfaces significantly alter the high-frequency
      mechanical response of this important material. 

PMID- 24077086
TI  - [Treatment of primary thyroid lymphomas].
AB  - Primary lymphomas of the thyroid (LPT) are a rare entity. LPT represent between 5
      and 15% of all thyroid neoplasms. Cytology has limited value; biopsy should be
      recommended. The differential diagnosis of thyroid carcinoma is differentiated
      forms indolent or aggressive forms for anaplastic and high grade that may occur
      by a mass rapidly progressive and compressive. LPT represent a histologically and
      clinically heterogeneous disease. The most common forms are high-grade LPT
      (DBLCL) of diffuse large cell type or mucosa-associated lymphoid tissue (MALT).
      DBLCL receive chemotherapy. The benefit of irradiation is highly debated in view
      of the data from randomized lymphoma studies (nodal with a minority of extranodal
      forms) versus those of retrospective studies specifically addressing the case of
      LPT. Localized MALT lymphomas can be treated with radiation alone. The treatment
      of other LPT is presented. 

PMID- 24077087
TI  - Correlation of fundus autofluorescence with foveal microstructures and vision in
      branch retinal vein occlusion.
AB  - PURPOSE: To investigate the correlation of fundus autofluorescence (FAF) with the
      findings of spectral domain optical coherence tomography and visual acuity in
      patients with branch retinal vein occlusion and to determine the visual
      prognostic factors. METHODS: Retrospectively, an evaluation of FAF, spectral
      domain optical coherence tomography images, and visual acuity before and after
      intravitreal injection of bevacizumab (pre- and post-IVB) was obtained in 42
      patients with branch retinal vein occlusion who underwent IVB as their first
      treatment. The FAF of fovea was graded on a scale of 1 to 4. RESULTS: The visual
      acuity post-IVB was associated with the visual acuity pre-IVB. Preservation of
      external limiting membrane and photoreceptor inner and outer segment junction pre
      and post-IVB were associated with better visual acuity post-IVB. Eyes with less
      FAF pre-IVB were closely associated with better visual acuity post-IVB.
      CONCLUSION: The shorter length of photoreceptor inner and outer segment junction
      and external limiting membrane defect and less FAF pre-IVB showed a significant
      association with better visual acuity post-IVB. These associations could help to
      predict potential restoration of photoreceptor integrity and visual recovery in
      patients with branch retinal vein occlusion, in whom photoreceptor integrity
      before treatment could not be adequately evaluated, even with spectral domain
      optical coherence tomography.

PMID- 24077088
TI  - Intravitreal pharmacokinetics after posterior subtenon triamcinolone acetonide
      injection in vitrectomized rabbit eyes.
AB  - PURPOSE: To investigate the intraocular pharmacokinetics of triamcinolone
      acetonide (TA) injected into the posterior subtenon of vitrectomized rabbit eyes.
      METHODS: Vitrectomy was performed on the right eyes of 35 rabbits. Triamcinolone
      acetonide (40 mg/mL) was injected into the posterior subtenon space of both eyes.
      Five rabbits each were killed at days 1, 3, 7, 14, 28, 56, and 84. Both eyes were
      enucleated. The vitreous was isolated, and TA concentration was measured.
      RESULTS: In vitrectomized eyes, the intravitreal concentrations of TA were 1763,
      822.9, 321.5, 113.3, 35.5, 14.4, and 6.7 ng/mL, respectively, at the time points
      indicated above; the concentrations in nonvitrectomized eyes were 397.8, 360.4,
      154.4, 48.5, 30.7, 15.2, and 8.0 ng/mL, respectively. Triamcinolone acetonide
      concentrations were significantly higher in the vitrectomized eyes at days 1, 3,
      7, and 14. The terminal half-life of intravitreal TA was 23.3 days in the
      vitrectomized eyes and 28.9 days in the nonvitrectomized eyes. CONCLUSION:
      Intravitreal absorption and excretion of TA in the posterior subtenon space are
      increased after vitrectomy. Although the terminal half-life of TA was shorter,
      higher early concentration and similar effective duration were achieved in the
      vitrectomized eyes.

PMID- 24077089
TI  - Restoration of retinal layers after epiretinal membrane peeling.
AB  - PURPOSE: To evaluate the morphologic restoration of retinal anatomy after surgery
      for epiretinal membrane (ERM) peeling using spectral domain optical coherence
      tomography. Correlation of retinal structure with visual outcome. DESIGN:
      Retrospective consecutive case series. METHODS: Thirty-four consecutive eyes with
      ERM underwent surgery with 1 year follow-up examination. Spectral domain optical
      coherence tomography scans were analyzed preoperatively and 1, 3, 6, 9, and 12
      months postoperative. Best-corrected visual acuity (BCVA) using Early Treatment
      Diabetic Retinopathy Study charts was measured at each visit. RESULTS: All eyes
      showed a significant improvement of BCVA after ERM peeling (P = 0.002). The time
      point of BCVA and retinal restoration seen on spectral domain optical coherence
      tomography occurred simultaneously and varied between individuals (occurrence of
      BCVA: mean, 4.82 months; retinal restoration: mean, 4.24 months). At 3 months,
      the retinal anatomical restoration rate was 70% and 88% at 6 months. CONCLUSION:
      Restoration of the retinal anatomical structure predominantly occurs within the
      first 3 months post-ERM peeling. An improvement of BCVA and anatomical retinal
      restoration after ERM removal varies in individuals. If retinal layers fully
      restore in their anatomical structure, BCVA improves at the same time point.

PMID- 24077090
TI  - Glial cells and collagens in epiretinal membranes associated with idiopathic
      macular holes.
AB  - PURPOSE: To investigate the identity of collagens and cellular components in the
      epiretinal membrane (ERM) associated with full-thickness idiopathic macular hole
      and their clinical relevance. METHODS: Pars plana vitrectomy with the peeling of
      internal limiting membrane and ERM was performed by 2 surgeons in 40 eyes with
      idiopathic macular holes. The clinical data were reviewed and the surgical
      specimens were processed for flat-mount and immunohistochemical analysis.
      RESULTS: Epiretinal membrane is a GFAP-positive gliotic and fibrotic scar which
      contains newly formed Type I, III, and V collagens. Type VI collagen was not
      observed. Colocalization studies found cells coexpressing GFAP/CRALBP, GFAP/alpha
      SMA, and alpha-SMA/CRALBP, which are consistent with transdifferentiation of
      Muller cells into fibroblasts and myofibroblasts. The clinically significant ERMs
      can be divided into two groups according to the amount of cells in ERM: sparse
      cellular proliferation and dense cellular proliferation. The latter group is
      associated with a higher chance of surgical difficulty during internal limiting
      membrane peeling (P = 0.006). Preoperative and postoperative visual function were
      not affected by the density of the cellular proliferation. CONCLUSION: Retinal
      glial cells, probably transdifferentiated Muller cells, are involved in the
      formation of full-thickness macular hole-associated ERMs by a gliotic and
      fibrotic process. Such ERMs contain newly formed Type I, III, and V collagen
      depositions. The cell density of ERM affects its biomechanical properties and
      determines the difficulty of ERM peeling.

PMID- 24077091
TI  - Validation of a method for reconstructing historical rates of smoking prevalence.
AB  - The validity of methods for reconstructing historical rates of smoking prevalence
      has not been assessed before. Our objective was to assess their validity. We
      reconstructed smoking prevalence rates for each calendar year from 1940 to 2007
      for men and women in Spain, using data on ages of smoking initiation and
      cessation available in the Spanish National Health Surveys of 2003-2004 and 2006
      2007. To assess the validity of the reconstruction, we computed the differences
      between the reconstructed smoking prevalence and the contemporary observed
      smoking prevalence measured in the Spanish National Health Surveys of 1987, 1993,
      1995, 1997, and 2001. We also compared reconstructed smoking prevalence trends
      with 35-year lagged lung cancer mortality rates in Spain as a proxy for the real
      prevalence trends. Reconstructed smoking prevalence rates compared with
      contemporary measured rates showed small differences in men (between -2.1% and
      2.1%) and an overestimation in women (between 2.0% and 5.7%). Reconstructed
      smoking prevalence trends were significantly correlated with lagged lung cancer
      mortality trends (P = 0.004 for men, P < 0.0001 for women). The reconstruction of
      smoking prevalence rates through this methodology offers a feasible tool with
      which countries lacking previous smoking surveys can understand historical trends
      in their tobacco epidemic, which aids in designing and implementing adequate
      tobacco control interventions.

PMID- 24077092
TI  - Causal inference in occupational epidemiology: accounting for the healthy worker
      effect by using structural nested models.
AB  - In a recent issue of the Journal, Kirkeleit et al. (Am J Epidemiol.
      2013;177(11):1218-1224) provided empirical evidence for the potential of the
      healthy worker effect in a large cohort of Norwegian workers across a range of
      occupations. In this commentary, we provide some historical context, define the
      healthy worker effect by using causal diagrams, and use simulated data to
      illustrate how structural nested models can be used to estimate exposure effects
      while accounting for the healthy worker survivor effect in 4 simple steps. We
      provide technical details and annotated SAS software (SAS Institute, Inc., Cary,
      North Carolina) code corresponding to the example analysis in the Web Appendices,
      available at http://aje.oxfordjournals.org/. 

PMID- 24077093
TI  - Self-controlled case series and misclassification bias induced by case selection
      from administrative hospital databases: application to febrile convulsions in
      pediatric vaccine pharmacoepidemiology.
AB  - Vaccine safety studies are increasingly conducted by using administrative health
      databases and self-controlled case series designs that are based on cases only.
      Often, several criteria are available to define the cases, which may yield
      different positive predictive values, as well as different sensitivities, and
      therefore different numbers of selected cases. The question then arises as to
      which is the best case definition. This article proposes new methodology to guide
      this choice based on the bias of the relative incidence and the power of the
      test. We apply this methodology in a validation study of 4 nested algorithms for
      identifying febrile convulsions from the administrative databases of 10 French
      hospitals. We used a sample of 695 children aged 1 month to 3 years who were
      hospitalized in 2008-2009 with at least 1 diagnosis code of febrile convulsions.
      The positive predictive values of the algorithms ranged from 81% to 98%, and
      their sensitivities were estimated to be 47%-99% in data from 1 large hospital.
      When applying our proposed methods, the algorithm we selected used a restricted
      diagnosis code and position on the discharge abstract. These criteria, which
      resulted in the selection of 502 cases with a positive predictive value of 95%,
      provided the best compromise between high power and low relative bias. 

PMID- 24077094
TI  - Sorption behavior of 20 wastewater originated micropollutants in groundwater-
      column experiments with pharmaceutical residues and industrial agents.
AB  - Since sorption is an essential process with regard to attenuation of organic
      pollutants during subsurface flow, information on the sorption properties of each
      pollutant are essential for assessing their environmental fate and transport
      behavior. In the present study, the sorption behavior of 20 wastewater originated
      organic micropollutants was assessed by means of sediment column experiments,
      since experimentally determined data for these compounds are not or sparsely
      represented in the literature. Compounds investigated include various
      psychoactive drugs, phenazone-type pharmaceuticals and beta-blockers, as well as
      phenacetine, N-methylphenacetine, tolyltriazole and para-toluenesulfonamide.
      While for most of the compounds no or only a low sorption affinity was observed,
      an elevated tendency to sorb onto aquifer sand was obtained for the beta-blockers
      atenolol, propranolol and metoprolol. A comparison between experimental data and
      data estimated based on the octanol/water partition coefficient following the
      QSAR approach demonstrated the limitations of the latter to predict the
      adsorption behavior in natural systems for the studied compounds. 

PMID- 24077096
TI  - Factors influencing patients' dignity: A qualitative study.
AB  - Dignity represents the essence of nursing care; hence, nurses are professionally
      responsible for promoting understanding about the promotion, provision, and
      preservation of every patient's dignity, while considering contextual
      differences. The aim of this study was to explore the factors that influence,
      promote, or compromise patient dignity. A purposeful sample of 14 participants
      with hospitalization experience was chosen, and individual in-depth semi
      structured interviews were conducted for data collection. Using inductive content
      analysis, the themes and subthemes related to factors influencing patients'
      dignity were explored: "persona" ("personal beliefs" and "personal
      characteristics"), "communication behaviors" ("verbal interaction," "body
      language," "compassionate behavior," and "devoting enough time"), and "staff
      conduct" ("professional commitment," "adequate human resources," and "staff's
      proficiency and competency"). The findings revealed that it is essential to
      expand nurses' insights and knowledge about preserving patients' dignity and the
      factors that influence these. Recognizing and focusing on these factors will help
      nurses to establish practical measures for preserving and promoting patients'
      dignity and providing more dignified care at the bedside. 

PMID- 24077095
TI  - Hypothalamic-pituitary-adrenal axis effects of mometasone furoate/formoterol
      fumarate vs fluticasone propionate/salmeterol administered through metered-dose
      inhaler.
AB  - BACKGROUND: The effects of mometasone furoate and fluticasone propionate on the
      hypothalamic-pituitary-adrenal axis were compared when administered from
      combination metered-dose inhaler (MDI) products. METHODS: In a randomized, open
      label, placebo-controlled, parallel group study, 66 patients with mild to
      moderate asthma received one of the following four treatments bid through an MDI
      for 42 days: mometasone furoate/formoterol (MF/F) 200 MUg/10 MUg, MF/F 400 MUg/10
      MUg, fluticasone propionate/salmeterol (FP/S) 460 MUg/42 MUg, or placebo. Plasma
      cortisol concentrations were measured over 24 h on days -1 (baseline) and 42.
      Geometric mean ratio (GMR) and 90% CI for mean change from baseline to day 42 in
      24-h plasma cortisol area under the curve (AUC) were calculated for each
      treatment. If the 90% CI for the GMRs fell within 70% to 143%, treatments were
      deemed comparable. RESULTS: Mean baseline cortisol AUCs were similar across
      groups. Mean cortisol effects (change from baseline) were similar for MF/F 400
      MUg/10 MUg and FP/S 460 MUg/42 MUg (GMR, 119%; 90% CI, 101%-140%). Effects of
      MF/F 200 MUg/10 MUg on cortisol AUC were similar to placebo (GMR, 92%; 90% CI,
      78%-110%), whereas MF/F 400 MUg/10 MUg and FP/S 460 MUg/42 MUg lowered cortisol
      AUC vs placebo (GMR, 78% [90% CI, 66%-92%] and 66% [90% CI 56%-78%],
      respectively). All treatments were generally well tolerated. CONCLUSIONS: MF/F
      400 MUg/10 MUg or FP/S 460 MUg/42 MUg bid through an MDI led to similar
      reductions from baseline in mean cortisol AUC (22% and 34% lower than placebo,
      respectively), whereas the effect of MF/F 200 MUg/10 MUg was similar to placebo.

PMID- 24077097
TI  - Microbial production of short-chain alkanes.
AB  - Increasing concerns about limited fossil fuels and global environmental problems
      have focused attention on the need to develop sustainable biofuels from renewable
      resources. Although microbial production of diesel has been reported, production
      of another much in demand transport fuel, petrol (gasoline), has not yet been
      demonstrated. Here we report the development of platform Escherichia coli strains
      that are capable of producing short-chain alkanes (SCAs; petrol), free fatty
      acids (FFAs), fatty esters and fatty alcohols through the fatty acyl (acyl
      carrier protein (ACP)) to fatty acid to fatty acyl-CoA pathway. First, the beta
      oxidation pathway was blocked by deleting the fadE gene to prevent the
      degradation of fatty acyl-CoAs generated in vivo. To increase the formation of
      short-chain fatty acids suitable for subsequent conversion to SCAs in vivo, the
      activity of 3-oxoacyl-ACP synthase (FabH), which is inhibited by unsaturated
      fatty acyl-ACPs, was enhanced to promote the initiation of fatty acid
      biosynthesis by deleting the fadR gene; deletion of the fadR gene prevents
      upregulation of the fabA and fabB genes responsible for unsaturated fatty acids
      biosynthesis. A modified thioesterase was used to convert short-chain fatty acyl
      ACPs to the corresponding FFAs, which were then converted to SCAs by the
      sequential reactions of E. coli fatty acyl-CoA synthetase, Clostridium
      acetobutylicum fatty acyl-CoA reductase and Arabidopsis thaliana fatty aldehyde
      decarbonylase. The final engineered strain produced up to 580.8 mg l(-1) of SCAs
      consisting of nonane (327.8 mg l(-1)), dodecane (136.5 mg l(-1)), tridecane (64.8
      mg l(-1)), 2-methyl-dodecane (42.8 mg l(-1)) and tetradecane (8.9 mg l(-1)),
      together with small amounts of other hydrocarbons. Furthermore, this platform
      strain could produce short-chain FFAs using a fadD-deleted strain, and short
      chain fatty esters by introducing the Acinetobacter sp. ADP1 wax ester synthase
      (atfA) and the E. coli mutant alcohol dehydrogenase (adhE(mut)). 

PMID- 24077098
TI  - Diabetic hyperglycaemia activates CaMKII and arrhythmias by O-linked
      glycosylation.
AB  - Ca(2+)/calmodulin-dependent protein kinase II (CaMKII) is an enzyme with
      important regulatory functions in the heart and brain, and its chronic activation
      can be pathological. CaMKII activation is seen in heart failure, and can directly
      induce pathological changes in ion channels, Ca(2+) handling and gene
      transcription. Here, in human, rat and mouse, we identify a novel mechanism
      linking CaMKII and hyperglycaemic signalling in diabetes mellitus, which is a key
      risk factor for heart and neurodegenerative diseases. Acute hyperglycaemia causes
      covalent modification of CaMKII by O-linked N-acetylglucosamine (O-GlcNAc). O
      GlcNAc modification of CaMKII at Ser 279 activates CaMKII autonomously, creating
      molecular memory even after Ca(2+) concentration declines. O-GlcNAc-modified
      CaMKII is increased in the heart and brain of diabetic humans and rats. In
      cardiomyocytes, increased glucose concentration significantly enhances CaMKII
      dependent activation of spontaneous sarcoplasmic reticulum Ca(2+) release events
      that can contribute to cardiac mechanical dysfunction and arrhythmias. These
      effects were prevented by pharmacological inhibition of O-GlcNAc signalling or
      genetic ablation of CaMKIIdelta. In intact perfused hearts, arrhythmias were
      aggravated by increased glucose concentration through O-GlcNAc- and CaMKII
      dependent pathways. In diabetic animals, acute blockade of O-GlcNAc inhibited
      arrhythmogenesis. Thus, O-GlcNAc modification of CaMKII is a novel signalling
      event in pathways that may contribute critically to cardiac and neuronal
      pathophysiology in diabetes and other diseases. 

PMID- 24077099
TI  - Synthetic non-oxidative glycolysis enables complete carbon conservation.
AB  - Glycolysis, or its variations, is a fundamental metabolic pathway in life that
      functions in almost all organisms to decompose external or intracellular sugars.
      The pathway involves the partial oxidation and splitting of sugars to pyruvate,
      which in turn is decarboxylated to produce acetyl-coenzyme A (CoA) for various
      biosynthetic purposes. The decarboxylation of pyruvate loses a carbon equivalent,
      and limits the theoretical carbon yield to only two moles of two-carbon (C2)
      metabolites per mole of hexose. This native route is a major source of carbon
      loss in biorefining and microbial carbon metabolism. Here we design and construct
      a non-oxidative, cyclic pathway that allows the production of stoichiometric
      amounts of C2 metabolites from hexose, pentose and triose phosphates without
      carbon loss. We tested this pathway, termed non-oxidative glycolysis (NOG), in
      vitro and in vivo in Escherichia coli. NOG enables complete carbon conservation
      in sugar catabolism to acetyl-CoA, and can be used in conjunction with CO2
      fixation and other one-carbon (C1) assimilation pathways to achieve a 100% carbon
      yield to desirable fuels and chemicals. 

PMID- 24077100
TI  - Cell intrinsic immunity spreads to bystander cells via the intercellular transfer
      of cGAMP.
AB  - The innate immune defence of multicellular organisms against microbial pathogens
      requires cellular collaboration. Information exchange allowing immune cells to
      collaborate is generally attributed to soluble protein factors secreted by
      pathogen-sensing cells. Cytokines, such as type I interferons (IFNs), serve to
      alert non-infected cells to the possibility of pathogen challenge. Moreover, in
      conjunction with chemokines they can instruct specialized immune cells to contain
      and eradicate microbial infection. Several receptors and signalling pathways
      exist that couple pathogen sensing to the induction of cytokines, whereas
      cytosolic recognition of nucleic acids seems to be exquisitely important for the
      activation of type I IFNs, master regulators of antiviral immunity. Cytosolic DNA
      is sensed by the receptor cyclic GMP-AMP (cGAMP) synthase (cGAS), which catalyses
      the synthesis of the second messenger cGAMP(2'-5'). This molecule in turn
      activates the endoplasmic reticulum (ER)-resident receptor STING, thereby
      inducing an antiviral state and the secretion of type I IFNs. Here we find in
      murine and human cells that cGAS-synthesized cGAMP(2'-5') is transferred from
      producing cells to neighbouring cells through gap junctions, where it promotes
      STING activation and thus antiviral immunity independently of type I IFN
      signalling. In line with the limited cargo specificity of connexins, the proteins
      that assemble gap junction channels, most connexins tested were able to confer
      this bystander immunity, thus indicating a broad physiological relevance of this
      local immune collaboration. Collectively, these observations identify cGAS
      triggered cGAMP(2'-5') transfer as a novel host strategy that serves to rapidly
      convey antiviral immunity in a transcription-independent, horizontal manner. 

PMID- 24077101
TI  - When LPS sneaks into the cell.

PMID- 24077102
TI  - Divergent Reaction Pathways for Phenol Arylation by Arynes: Synthesis of
      Helicenes and 2-Arylphenols.
AB  - Two reactions of phenols with arynes have been developed. If LiTMP base is
      employed, arynes generated from aryl chlorides react with phenols to form
      helicenes. o-Arylation of phenols can be achieved by employing tBuONa base in the
      presence of AgOAc. Direct arylation of binol was achieved leading to the shortest
      pathway to o,o'-diarylbinols.

PMID- 24077104
TI  - A device for measuring spin selectivity in electron transfer.
AB  - A new type of device is presented that allows direct measurement of spin
      selectivity in charge transfer processes occurring in adsorbed molecules. The new
      device provides direct information about the nature of the charge being
      transferred (electrons or holes) and on spin selectivity, if it exists. Here the
      device is applied for establishing the spin-dependent electron transfer through
      double-stranded DNA and its variation with the length of the oligomer. The DNA is
      self-assembled on a silver substrate and is measured under ambient conditions.
      The device is based on monitoring the electric potential between a ferromagnetic
      Ni layer and a silver layer, on top of which the DNA is self-assembled. When a
      dye molecule, attached to the DNA, is photoexcited, a charge transfer between the
      dye and the silver substrate takes place, resulting in a change in the electric
      potential between the Ni and the silver. If the charge transfer is spin
      selective, the electric potential measured depends on the direction of
      magnetization of the Ni. 

PMID- 24077105
TI  - Increasing maximum tumor dose to manage range uncertainties in IMPT treatment
      planning.
AB  - The accuracy of intensity modulated proton therapy (IMPT) is sensitive to range
      uncertainties. Geometric margins, as dosimetric surrogates, are ineffective and
      robust optimization strategies are needed. These, however, lead to increased
      normal tissue dose. We explore here how this dose increase can be reduced by
      increasing the maximum tumor dose instead. We focus on range uncertainties,
      modeled by scaling the stopping powers 5% up (undershoot) or down (overshoot)
      compared to the nominal scenario. Robust optimization optimizes for target dose
      conformity in the most likely scenario, not the worst, while constraining target
      coverage for the worst-case scenario. Non-robust plans are also generated.
      Different maximum target doses are applied (105% versus 120% versus 140%) to
      investigate the effect on normal tissue dose reduction. The method is tested on a
      homogeneous and a lung phantom and on a liver patient. Target D99 of the robust
      plans equals the prescription dose of 60 GyE for all scenarios, but decreases to
      36 GyE for the non-robust plans. The mean normal tissue dose in a 2 cm ring
      around the target is 11% to 31% higher for the robust plans. This increase can be
      reduced to -8% and 3% (compared to the non-robust plan) by allowing a maximum
      tumor dose of 120% instead of 105%. Thus robustness leads to more normal tissue
      dose, but it can be compensated by allowing a higher maximum tumor dose. 

PMID- 24077103
TI  - Cancer cell glycocalyx mediates mechanotransduction and flow-regulated invasion.
AB  - Mammalian cells are covered by a surface proteoglycan (glycocalyx) layer, and it
      is known that blood vessel-lining endothelial cells use the glycocalyx to sense
      and transduce the shearing forces of blood flow into intracellular signals. Tumor
      cells in vivo are exposed to forces from interstitial fluid flow that may affect
      metastatic potential but are not reproduced by most in vitro cell motility
      assays. We hypothesized that glycocalyx-mediated mechanotransduction of
      interstitial flow shear stress is an un-recognized factor that can significantly
      enhance metastatic cell motility and play a role in augmentation of invasion.
      Involvement of MMP levels, cell adhesion molecules (CD44, alpha3 integrin), and
      glycocalyx components (heparan sulfate and hyaluronan) was investigated in a
      cell/collagen gel suspension model designed to mimic the interstitial flow
      microenvironment. Physiological levels of flow upregulated MMP levels and
      enhanced the motility of metastatic cells. Blocking the flow-enhanced expression
      of MMP activity or adhesion molecules (CD44 and integrins) resulted in blocking
      the flow-enhanced migratory activity. The presence of a glycocalyx-like layer was
      verified around tumor cells, and the degradation of this layer by hyaluronidase
      and heparinase blocked the flow-regulated invasion. This study shows for the
      first time that interstitial flow enhancement of metastatic cell motility can be
      mediated by the cell surface glycocalyx - a potential target for therapeutics. 

PMID- 24077106
TI  - Analytical methods for quantitation of prenylated flavonoids from hops.
AB  - The female flowers of hops (Humulus lupulus L.) are used as a flavoring agent in
      the brewing industry. There is growing interest in possible health benefits of
      hops, particularly as estrogenic and chemopreventive agents. Among the possible
      active constituents, most of the attention has focused on prenylated flavonoids,
      which can chemically be classified as prenylated chalcones and prenylated
      flavanones. Among chalcones, xanthohumol (XN) and desmethylxanthohumol (DMX) have
      been the most studied, while among flavanones, 8-prenylnaringenin (8-PN) and 6
      prenylnaringenin (6-PN) have received the most attention. Because of the interest
      in medicinal properties of prenylated flavonoids, there is demand for accurate,
      reproducible and sensitive analytical methods to quantify these compounds in
      various matrices. Such methods are needed, for example, for quality control and
      standardization of hop extracts, measurement of the content of prenylated
      flavonoids in beer, and to determine pharmacokinetic properties of prenylated
      flavonoids in animals and humans. This review summarizes currently available
      analytical methods for quantitative analysis of the major prenylated flavonoids,
      with an emphasis on the LC-MS and LC-MS-MS methods and their recent applications
      to biomedical research on hops. This review covers all methods in which
      prenylated flavonoids have been measured, either as the primary analytes or as a
      part of a larger group of analytes. The review also discusses methodological
      issues relating to the quantitative analysis of these compounds regardless of the
      chosen analytical approach.

PMID- 24077107
TI  - Effects of Millettia macrophylla (Fabaceae) extracts on estrogen target organs of
      female wistar rat.
AB  - The present study aims to determine the estrogenicity of Millettia macrophylla, a
      Cameroonian medicinal plant, in ovariectomized rats and to investigate the
      underlying mechanisms, in order to justify scientifically its traditional use. To
      accomplish this objective, we used dichloromethane (DCM) and methanol (MeOH)
      extracts of the stem bark of M. macrophylla. In the cell culture based assay, the
      MeOH extract significantly transactivated estrogen receptor alpha (ERalpha) and
      estrogen receptor beta (ERbeta); in addition, the estrogen-like effects of both,
      DCM and MeOH extracts, could be inhibited in vitro by the pure ER antagonist ICI
      182,780, indicating that these effects were primarily mediated through ERs. In
      animal experiments, both DCM and MeOH extracts significantly increased the
      uterine and vaginal epithelial heights in the 3-day treatment assay, while only
      the MeOH extract exhibited such effects in the sub-chronic treatment regimen.
      Furthermore, the MeOH extract significantly decreased fasting serum
      triglycerides, total cholesterol levels and artherogenic risk in the sub-chronic
      treatment. These results indicate that M. macrophylla extracts have estrogen-like
      effects supporting their traditional use in Cameroon to alleviate some menopausal
      problems (See graphical abstract in Supplementary Fig. 1, available in the online
      version only). 

PMID- 24077108
TI  - Perinatal exposure to low-dose bisphenol A impairs spatial learning and memory in
      male rats.
AB  - Bisphenol A (BPA) is an estrogenic endocrine disruptor used for producing
      polycarbonate plastics and epoxy resins. This study investigated the effects of
      perinatal BPA exposure on learning and memory, general activity, and emotionality
      in male Sprague Dawley rats using a battery of behavioral tests, including an
      appetite-motivated maze test (MAZE test) used to assess spatial learning and
      memory. Mother rats were orally administered BPA (50 or 500 MUg?kg(-1)/day) or
      vehicle (1 ml?kg(-1)/day) from gestational day 10 to postnatal day 14. In the
      MAZE test, compared to the offspring of vehicle-treated rat mothers, male
      offspring of mothers exposed to 50 MUg?kg(-1)/day of BPA, but not those of
      mothers exposed to 500 MUg?kg(-1)/day of BPA, needed significantly more time to
      reach the reward. Although male offspring of mothers exposed to 50 MUg?kg(-1)/day
      of BPA showed an increase in a behavioral measure of wariness after repeated
      testing in the open-field test, no significant effects were observed in locomotor
      activities. No significant differences were observed in any other behavioral test
      including the elevated plus-maze test. The present study suggests that perinatal
      exposure to low-dose BPA specifically and non-monotonically impairs spatial
      learning and memory in male offspring rats. 

PMID- 24077109
TI  - Endothelin receptor signaling: new insight into its regulatory mechanisms.
AB  - The endothelin (ET) system consists of two G protein coupled-receptors (GPCRs),
      ET type A receptor (ETAR) and ET type B receptor (ETBR), and three endogenous
      ligands, ET-1, ET-2, and ET-3. Stimulation of ETRs with ET-1 induces an increase
      in intracellular Ca(2+) concentration that is involved in a diverse array of
      physiological and pathophysiological processes, including vasoconstriction, and
      cell proliferation. Store-operated Ca(2+) entry and receptor-operated Ca(2+)
      entry triggered by activation of ETRs are regulated or modulated by endoplasmic
      reticulum Ca(2+) sensor (stromal interaction molecule 1) and voltage-independent
      cation channels (transient receptor potential canonical channels and Orai1). The
      ET-1-induced Ca(2+) mobilization results from activation of heterotrimeric G
      proteins by ETRs. In contrast, GPCR biology including modulation of receptor
      function and trafficking is regulated by a variety of GPCR interacting proteins
      (GIPs) that generally interact with the C-terminal domain of GPCRs. The ETR
      signaling is also regulated by GIPs such as Jun activation domain-binding protein
      1. This review focuses on the regulatory mechanisms of the ETR signaling with
      special attention to the components involved in Ca(2+) signaling and to GIPs in
      the signal transduction, modification, and degradation of ETRs. 

PMID- 24077110
TI  - [Clinical, diagnostic significance and theranostic interest of PIK3CA gene
      mutations in breast cancer].
AB  - Breast cancer is the most common cancer among women with more than 53,000 new
      cases every year in France. The PI3K/AKT pathway is one of the major pathways
      involved in mammary tumorigenesis. The first effector of this pathway downstream
      Human Epidermal growth factor Receptor (HER receptors) is the enzyme phosphatidyl
      inositol-3-kinase (PI3K). Some mutations in the gene encoding for the catalytic
      subunit of this enzyme, the PIK3CA gene, plays an important role, especially in
      the resistance to targeted therapies used clinically during the last decade.
      Indeed, the presence of alterations, an overexpression of the PI3K/AKT pathway,
      or the presence of PIK3CA mutation could explain some resistance to targeted
      therapies. PIK3CA mutations also appear to have a significant interest in the
      prediction of response to targeted therapies. Finally, many drugs in development,
      specifically targeting PI3K or other effectors of the PI3K/AKT pathway are
      intended to be administered only to patients with tumor bearing a mutation of
      PIK3CA, which makes the somatic mutations detection more and more important. The
      aim of this article is to consider biological aspects, clinical significance,
      diagnostic and theranostic interest of PIK3CA mutations in breast cancer. 

PMID- 24077111
TI  - Antimicrobial activity and cytocompatibility of Ag plasma-modified hierarchical
      TiO2 film on titanium surface.
AB  - To improve the antimicrobial ability and cytocompatibility of biomedical titanium
      implants, many efforts have been made to modify their surface topography and
      chemical composition. In this work, Ag plasma-modified hierarchical TiO2 film was
      fabricated on titanium surface via acid etching to produce micropit, hydrothermal
      treatment to generate TiO2 nanorod and subsequent plasma immersion ion
      implantation process to impregnate Ag into TiO2 surface. In view of the potential
      clinical applications, their antimicrobial activity, bioactivity and
      cytocompatibility were systematically evaluated. The hierarchical TiO2 film
      showed enhanced bioactivity and bacteriostatic effect on both microbes due to
      more negative zeta potential, constructing the first defense line against
      microbial adhesion by electrostatic repulsion. Addition of embedded Ag remarkably
      enhanced the antimicrobial efficiency toward both microbes based on Schottky
      contact without Ag(+) release, establishing the second defense line targeting
      microbial membrane. Furthermore, the addition of Ag degraded the bioactivity very
      little and exerted nearly no adverse or even promoted effect on MG63 cell
      functions, including adhesion, spreading and proliferation. This work illustrates
      a two-defense-line antimicrobial activity in darkness with both prior
      electrostatic repulsion to inhibit most microbes adhesion and posterior biocidal
      action to kill residual ones that luckily infiltrated through the first defense
      line, and provide proof of concept using both clinically relevant human
      pathogens. In conclusion, the Ag-embedded hierarchical TiO2 film with excellent
      antimicrobial activity, bioactivity and cytocompatibility provides a promising
      candidate for orthopedic and dental implants. 

PMID- 24077112
TI  - Alginate/cashew gum nanoparticles for essential oil encapsulation.
AB  - Alginate/cashew gum nanoparticles were prepared via spray-drying, aiming at the
      development of a biopolymer blend for encapsulation of an essential oil.
      Nanoparticles were characterized regarding to their hydrodynamic volume, surface
      charge, Lippia sidoides essential oil content and release profile, in addition to
      being analyzed by infrared spectroscopy (FT-IR), thermal analysis (TGA/DSC) and X
      ray diffractometry. Nanoparticles in solution were found to have averaged sizes
      in the range 223-399 nm, and zeta potential values ranging from -30 to -36 mV.
      Encapsulated oil levels varied from 1.9 to 4.4% with an encapsulation efficiency
      of up to 55%. The in vitro release profile showed that between 45 and 95% of oil
      was released within 30-50h. Kinetic studies revealed that release pattern follow
      a Korsmeyer-Peppas mechanism.

PMID- 24077113
TI  - Solid state characterisation of silver sulfadiazine loaded on
      montmorillonite/chitosan nanocomposite for wound healing.
AB  - Biopolymer chitosan/montmorillonite nanocomposites loaded with silver
      sulfadiazine for wound healing purposes were prepared via intercalation solution
      technique. Structure and morphology of loaded nanocomposites were studied and
      compared with pure components and unloaded nanocomposites. X-ray diffraction,
      Fourier transformed infrared spectroscopy, high resolution transmission electron
      microscopy coupled with energy-dispersion X-ray analysis, thermal and elemental
      analysis were employed for the characterisation. The results confirmed that the
      drug was effectively loaded in the three-dimensional nanocomposite structures, in
      which chitosan chains were adsorbed in monolayers into the clay mineral
      interlayer spaces. 

PMID- 24077114
TI  - Micellar nanoparticles loaded with gemcitabine and doxorubicin showed synergistic
      effect.
AB  - Gemcitabine and doxorubicin were separately chemically linked to biodegradable
      polymers to prepare polymer-gemcitabine and polymer-doxorubicin conjugates.
      Moreover, the two conjugates can self-assemble into micelles with both
      gemcitabine and doxorubicin. In this way, the two anticancer drugs were combined.
      The in vitro MTT assay with these combined drugs showed synergistic effect
      compared to single use of each drug. 

PMID- 24077115
TI  - Microbial ecology: a bacterial decoy skews plant defences.

PMID- 24077116
TI  - Demonstration of electron acceleration in a laser-driven dielectric
      microstructure.
AB  - The enormous size and cost of current state-of-the-art accelerators based on
      conventional radio-frequency technology has spawned great interest in the
      development of new acceleration concepts that are more compact and economical.
      Micro-fabricated dielectric laser accelerators (DLAs) are an attractive approach,
      because such dielectric microstructures can support accelerating fields one to
      two orders of magnitude higher than can radio-frequency cavity-based
      accelerators. DLAs use commercial lasers as a power source, which are smaller and
      less expensive than the radio-frequency klystrons that power today's
      accelerators. In addition, DLAs are fabricated via low-cost, lithographic
      techniques that can be used for mass production. However, despite several DLA
      structures having been proposed recently, no successful demonstration of
      acceleration in these structures has so far been shown. Here we report high
      gradient (beyond 250 MeV m(-1)) acceleration of electrons in a DLA. Relativistic
      (60-MeV) electrons are energy-modulated over 563 +/- 104 optical periods of a
      fused silica grating structure, powered by a 800-nm-wavelength mode-locked
      Ti:sapphire laser. The observed results are in agreement with analytical models
      and electrodynamic simulations. By comparison, conventional modern linear
      accelerators operate at gradients of 10-30 MeV m(-1), and the first linear radio
      frequency cavity accelerator was ten radio-frequency periods (one metre) long
      with a gradient of approximately 1.6 MeV m(-1) (ref. 5). Our results set the
      stage for the development of future multi-staged DLA devices composed of
      integrated on-chip systems. This would enable compact table-top accelerators on
      the MeV-GeV (10(6)-10(9) eV) scale for security scanners and medical therapy,
      university-scale X-ray light sources for biological and materials research, and
      portable medical imaging devices, and would substantially reduce the size and
      cost of a future collider on the multi-TeV (10(12) eV) scale. 

PMID- 24077117
TI  - Accelerating materials property predictions using machine learning.
AB  - The materials discovery process can be significantly expedited and simplified if
      we can learn effectively from available knowledge and data. In the present
      contribution, we show that efficient and accurate prediction of a diverse set of
      properties of material systems is possible by employing machine (or statistical)
      learning methods trained on quantum mechanical computations in combination with
      the notions of chemical similarity. Using a family of one-dimensional chain
      systems, we present a general formalism that allows us to discover decision rules
      that establish a mapping between easily accessible attributes of a system and its
      properties. It is shown that fingerprints based on either chemo-structural
      (compositional and configurational information) or the electronic charge density
      distribution can be used to make ultra-fast, yet accurate, property predictions.
      Harnessing such learning paradigms extends recent efforts to systematically
      explore and mine vast chemical spaces, and can significantly accelerate the
      discovery of new application-specific materials. 

PMID- 24077119
TI  - A highly sensitive and wide-ranged electrochemical zinc(II) aptasensor fabricated
      on core-shell SiO2-Pt@meso-SiO2.
AB  - In this work, bi-functional SiO2-Pt@meso-SiO2 core-shell nanoparticles were
      designed to prepare a highly sensitive and selective electrochemical zinc(II)
      aptasensor. This core-shell structure boasts its SiO2 mesoporous shell and the
      inside Pt nanoparticles. SiO2 mesoporous shell can fix aptamer without affecting
      its configuration and can admit electrolyte through the shell. SiO2 core inside
      can be the substrate of larger amount of Pt nanoparticles that improve the
      conductivity of the modified electrode dramatically. Due to the application of
      such a special bi-functional structure and the aptamer's strong combination
      capacity with Zn(2+), Zn(2+) is pre-enriched onto the electrode effectively and
      specifically, so that it can be determined sensitively and selectively. Results
      have shown that the zinc(II) aptasensor can be utilized at a wide linear working
      range from 100 pM to 50 MUM and a low detection limit of 65 pM, which makes it
      practical in both biological samples and environment monitoring. This method has
      been successfully applied in Zn(2+) monitoring in human blood and disrupted human
      cells (MCF-7).

PMID- 24077120
TI  - Prevention of chronic PTSD with early cognitive behavioral therapy. A meta
      analysis using mixed-effects modeling.
AB  - Post-traumatic stress disorder (PTSD) is of great interest to public health, due
      to the high burden it places on both the individual and society. We meta-analyzed
      randomized-controlled trials to examine the effectiveness of early trauma-focused
      cognitive-behavioral treatment (TFCBT) for preventing chronic PTSD. Systematic
      bibliographic research was undertaken to find relevant literature from on-line
      databases (Pubmed, PsycINFO, Psyndex, Medline). Using a mixed-effect approach, we
      calculated effect sizes (ES) for the PTSD diagnoses (main outcome) as well as
      PTSD and depressive symptoms (secondary outcomes), respectively. Calculations of
      ES from pre-intervention to first follow-up assessment were based on 10 studies.
      A moderate effect (ES = 0.54) was found for the main outcome, whereas ES for
      secondary outcomes were predominantly small (ES = 0.27-0.45). The ES for the main
      outcome decreased to small (ES = 0.34) from first follow-up to long-term follow
      up assessment. The mean dropout rate was 16.7% pre- to post-treatment. There was
      evidence for the impact of moderators on different outcomes (e.g., the number of
      sessions on PTSD symptoms). Future studies should include survivors of other
      trauma types (e.g., burn injuries) rather than predominantly survivors of
      accidents and physical assault, and should compare early TFCBT with other
      interventions that previously demonstrated effectiveness. 

PMID- 24077121
TI  - Semisynthesis and antifeedant activity of new derivatives of a dihydro-beta
      agarofuran from Parnassia wightiana.
AB  - Five new derivatives (2-6) were semi-synthesized using compound 1, a dihydro-beta
      agarofuran sesquiterpene with C-2 ketone obtained from Parnassia wightiana, as
      the starting material by acylation, oxidation, reduction, esterification, and
      amination, respectively. Structures of 2-6 were confirmed by 1D- and 2D-NMR and
      HR-ESI-MS spectra. In addition, antifeedant activities of these compounds (1-6)
      were tested against the 3rd-instar larvae of Mythimna separata. Antifeedant
      effects of compounds 2 and 4 were greater than the parent compound 1 whereas
      other compounds exhibited low to no feeding deterrent effects against third
      instar M. separata larvae in lab bioassays. Therefore, our results suggest that
      acylated and reduced derivatives at C-8 and C-2, respectively, of 1 may improve
      the antifeeding effect. This preliminary information will be useful in designing
      new insect control agents against M. separata and other important pests. 

PMID- 24077122
TI  - Molecular research in penile cancer-lessons learned from the past and bright
      horizons of the future?
AB  - Penile cancer is a rare tumor. There is a limited understanding of the biological
      mediators of prognostic and therapeutic importance in penile cancer. However,
      there exists some fundamental understanding of the major pathways involved in the
      development of penile pre-neoplastic lesions and neoplasms. The aim of the
      present review is to highlight our current state of molecular knowledge in penile
      cancer to foster the necessary tools for researchers to pave major advancements
      in our current treatment paradigms and cancer specific outcomes. 

PMID- 24077123
TI  - Single molecule studies on dynamics in liquid crystals.
AB  - Single molecule (SM) methods are able to resolve structure related dynamics of
      guest molecules in liquid crystals (LC). Highly diluted small dye molecules on
      the one hand explore structure formation and LC dynamics, on the other hand they
      report about a distortion caused by the guest molecules. The anisotropic
      structure of LC materials is used to retrieve specific conformation related
      properties of larger guest molecules like conjugated polymers. This in particular
      sheds light on organization mechanisms within biological cells, where large
      molecules are found in nematic LC surroundings. This review gives a short
      overview related to the application of highly sensitive SM detection schemes in
      LC. 

PMID- 24077124
TI  - Synthesis and activity of novel acylthiourea with hydantoin.
AB  - The 41 novel acylthiourea derivatives with hydantoin were synthesized in moderate
      to excellent yields by using 5-(4-aminophenyl)- and 5-(4-aminobenzyl)-hydantoin
      or 5-(4-aminobenzyl)-thiohydantoin as raw materials and characterized by IR, 1H
      NMR spectra and elementary analysis. The preliminary bioassay showed that these
      compounds exhibit certain selectively herbicidal activities with the 91%, 94% and
      87% inhibition rates of 7l, 8o and 8p against B. campestris, 100%, 100% and 95%
      efficacy against B. campestris in a greenhouse test, respectively. 7a, 7b, 7c and
      7d exhibited 74%, 79%, 79% and 71% inhibition rates against F. oxysporum,
      respectively. 

PMID- 24077125
TI  - Isolation and characterization of squamous cell carcinoma-derived stem-like
      cells: role in tumor formation.
AB  - In human epidermis, keratinocyte stem cells (KSC) are characterized by high
      levels of beta1-integrin, resulting in the rapid adhesion to type IV collagen.
      Since epithelial tumors originate from KSC, we evaluated the features of rapidly
      adhering (RAD) keratinocytes derived from primary human squamous cell carcinoma
      of the skin (cSCC). RAD cells expressed higher levels of survivin, a KSC marker,
      as compared to non-rapidly adhering (NRAD) cells. Moreover, RAD cells
      proliferated to a greater extent and were more efficient in forming colonies than
      NRAD cells. RAD cells also migrated significantly better than NRAD cells. When
      seeded in a silicone chamber and grafted onto the back skin of NOD SCID mice, RAD
      cells formed tumors 2-4 fold bigger than those derived from NRAD cells. In tumors
      derived from RAD cells, the mitotic index was significantly higher than in those
      derived from NRAD cells, while Ki-67 and survivin expression were more pronounced
      in RAD tumors. This study suggests that SCC RAD stem cells play a critical role
      in the formation and development of epithelial tumors. 

PMID- 24077126
TI  - Investigations of the binding of [Pt2(DTBPA)Cl2](II) and [Pt2(TPXA)Cl2](II) to
      DNA via various cross-linking modes.
AB  - We have constructed models for a series of platinum-DNA adducts that represent
      the binding of two agents, [Pt2(DTBPA)Cl2](II) and [Pt2(TPXA)Cl2](II), to DNA via
      inter- and intra-strand cross-linking, and carried out molecular dynamics
      simulations and DNA conformational dynamics calculations. The effects of trans-
      and cis-configurations of the centers of these di-nuclear platinum agents, and of
      different bridging linkers, have been investigated on the conformational
      distortions of platinum-DNA adducts formed via inter- and intra-strand cross
      links. The results demonstrate that the DNA conformational distortions for the
      various platinum-DNA adducts with differing cross-linking modes are greatly
      influenced by the difference between the platinum-platinum distance for the
      platinum agent and the platinum-bound N7-N7 distance for the DNA molecule, and by
      the flexibility of the bridging linkers in the platinum agent. However, the
      effects of trans/cis-configurations of the platinum-centers on the DNA
      conformational distortions in the platinum-DNA adducts depend on the inter- and
      intra-strand cross-linking modes. In addition, we discuss the relevance of DNA
      base motions, including opening, shift and roll, to the changes in the parameters
      of the DNA major and minor grooves caused by binding of the platinum agent. 

PMID- 24077127
TI  - Compression versus inner sole for venous patients with foot static disorders: a
      prospective trial comparing symptoms and quality of life.
AB  - OBJECTIVE: To prospectively compare the improvement in quality of life and
      symptoms achieved when using two treatments-medical compression stockings and
      inner sole-in subjects with symptomatic chronic venous disease in the presence of
      foot static disorders. MATERIALS AND METHODS: This prospective study included 24
      patients with a symptomatic chronic venous disease associated with foot static
      disorders. The basic CEAP was used to classify the patients. The venous symptoms
      were recorded using a 10-point visual analog scale and scored using a customized
      questionnaire. Patient-reported quality of life data were acquired using a CIVIC
      questionnaire. A standardized measurement of the Djian-Annonier angle was used to
      quantify the foot static disorders. We compared the use of the following two
      treatments: medical compression stockings (18 mm of Hg) and inner sole. For this
      comparison, we used a crossover technique over 4 successive weeks. RESULTS: One
      male and 23 female patients were included in this study. We found significant
      improvement in quality of life scores when only medical compression stockings
      were used (p < 0.005), only inner sole were used (p < 0.01) and also when both
      treatments were used together (p < 0.001), compared with no treatment. This was
      mainly observed for the somatic component of CIVIC. The symptoms of pain,
      heaviness, swollen feeling, and cramps were significantly improved by the two
      treatments, whether given separately (p < 0.001) or together (p < 0.0001). No
      additive effect of the treatments was observed. CONCLUSION: This study suggests
      that a number of leg symptoms occurring in varicose veins patients are not likely
      to have a venous origin. They are frequently related to a foot static disorder,
      which is responsible for postural changes. This study also strongly demonstrates
      the need for correction of the foot static disorder if such a disorder is present
      in any patient with chronic venous disease. The use of the inner sole will
      improve the symptoms and also the quality of life with an efficiency that is
      almost equal to that provided by the medical compression stockings and the
      combined use of both treatments is recommended.

PMID- 24077128
TI  - Small field dosimetric characterization of a new 160-leaf MLC.
AB  - The goal of this work was to perform a 6 MV small field characterization of the
      new Agility 160-leaf multi-leaf collimator (MLC) from Elekta. This included
      profile measurement analysis and central axis relative output measurements using
      various diode detectors and an air-core fiber optic scintillation dosimeter
      (FOD). Data was acquired at a depth of 10.0 cm for field sizes of 1.0, 0.9, 0.8,
      0.7, 0.6 and 0.5 cm. Three experimental data sets, comprised of five readings,
      were made for both the relative output and profile measurements. Average detector
      specific output ratios (OR[overline](f(clin))(det))) were calculated with respect
      to a field size of 3.0 cm and small field replacement correction factors
      (k(f(clin),f(msr))(Q(clin),Q(msr))) derived for the diodes using the
      scintillation dosimeter readings as the baseline. The standard experimental
      uncertainty on OR[overline](f(clin))(det)) was calculated at a 90% confidence
      interval and the coefficient of variation (CV) used to characterize the detector
      specific measurement precision. The positional accuracy of the collimation system
      was also investigated by analyzing the repeated profile measurements and field
      width constancy investigated as a function of collimator rotation. For comparison
      the output and profile measurements were repeated using the Elekta 80-leaf MLCi2
      on a beam matched linac at 6 MV. The measured OR[overline](f(clin))(det)) varied
      as a function of detector and MLC design. At the smallest field size the standard
      experimental uncertainty on OR[overline](f(clin))(det)) was consistent across all
      detectors at approximately 0.5% and 1.0% for Agility and MLCi2 collimators
      respectively. The CV associated with the FOD measurements were greater than that
      of the diodes but did not translate into increased measurement uncertainty. At
      the smallest field size, the diode detector correction factors were approximately
      2% greater for MLCi2 than that required for the Agility. Profile data revealed
      the Agility MLC to have a greater positional reproducibility than both the MLCi2
      and the linac diaphragms (jaws), as also reflected in the experimental
      uncertainties on OR[overline](f(clin))(det)). The relative output, profile widths
      and associated uncertainties were all found to differ between the two MLC systems
      investigated, as were the field size specific diode detector replacement
      correction factors. The data also clearly showed that the Agility 160-leaf MLC
      performs to a tighter positional tolerance than the MLCi2.

PMID- 24077129
TI  - A photoionization investigation of small, homochiral clusters of glycidol using
      circularly polarized radiation and velocity map electron-ion coincidence imaging.
AB  - A detailed study of the valence photoionization of small homochiral glycidol
      (C3O2H6) clusters is carried out with the help of circularly-polarized VUV
      synchrotron radiation by recording photoionization-based spectroscopic data
      detected by velocity map electron imaging with coincidence ion selection. We show
      that information on the stability of cationic as well as neutral chiral clusters
      can be obtained with enhanced sensitivity by examining the chiral fingerprint
      encapsulated in Photoelectron Circular Dichroism (PECD) spectra. In particular,
      by varying the clustering conditions we demonstrate that the PECD signal
      effectively carries the signature of the neutral precursor species, prior to any
      fragmentation of the ion, as may be inferred from the below-threshold monomer
      measurements (including ion imaging). Here the monomer's direct ionization
      channel is closed and the monomer ion hence must result exclusively as a fragment
      from dissociative ionization of the dimer (or higher) clusters. At higher photon
      energies, the mass-selection on the electron spectroscopy data, achieved through
      filtering the electron images in coincidence with selected ion masses, evidently
      succeeds in providing a degree of size-selection on the neutral clusters being
      ionized with, in particular, a clear differentiation of monomer and dimer PECD,
      showing the strong sensitivity of this chiroptical effect to the non-local long
      range molecular potential. 

PMID- 24077130
TI  - Parallel measurements of reaction kinetics using ultralow-volumes.
AB  - We present a new platform for the production and manipulation of microfluidic
      droplets in view of measuring the evolution of a chemical reaction. Contrary to
      existing approaches, our device uses gradients of confinement to produce a single
      drop on demand and guide it to a pre-determined location. In this way, two
      nanoliter drops containing different reagents can be placed in contact and merged
      together, in order to trigger a chemical reaction. The reaction rate is extracted
      from an analysis of the observed reaction-diffusion front. We show that the
      results obtained using this platform are in excellent agreement with stopped-flow
      measurements, while decreasing the sample consumption 5000 fold. We also show how
      the device operation can be parallelized in order to react an initial sample with
      a range of compounds or concentrations, on a single integrated chip. This
      integrated chip thus further reduces sample consumption while reducing the time
      required for the experimental runs from hours to minutes. 

PMID- 24077132
TI  - Combined tibial tubercle osteotomy with medial opening wedge high tibial
      osteotomy minimizes changes in patellar height: a prospective cohort study with
      historical controls.
AB  - BACKGROUND: Medial opening wedge high tibial osteotomy (HTO) for the treatment of
      varus gonarthrosis can be associated with inadvertent decreases in patellar
      height. HYPOTHESIS: Decreases in patellar height observed after medial opening
      wedge HTO can be minimized with the addition of a tibial tubercle osteotomy
      (TTO). STUDY DESIGN: Cohort study; Level of evidence, 3. METHODS: Twenty-nine
      patients undergoing medial opening wedge HTO with a concurrent TTO were matched
      with 29 controls who previously underwent medial opening wedge HTO without a TTO.
      Both groups had substantial varus malalignment (mean mechanical axis angle, -10
      degrees  +/- 3 degrees ) requiring large corrections. Measurements of patellar
      height and posterior tibial slope were calculated from standing lateral
      radiographs and compared preoperatively and 6 months postoperatively. Patellar
      height measures included the Blackburne-Peel index, Caton-Deschamps index, Miura
      Kawamura index, Insall-Salvati ratio, and modified Insall-Salvati ratio. RESULTS:
      The changes in the Blackburne-Peel, Caton-Deschamps, and Miura-Kawamura indices
      were significantly less in the HTO/TTO group versus the HTO group. There were 3
      of 29 (10%) new cases that met the radiographic criteria for patella infera in
      the HTO/TTO group versus 11 of 29 (38%) new cases of patella infera found
      postoperatively in the HTO group, suggesting an absolute risk reduction of 28%
      with TTO. The changes in the Blackburne-Peel and Caton-Deschamps indices were
      correlated to a larger preoperative varus deformity in the coronal plane (r =
      0.52 and r = 0.41, respectively). CONCLUSION: The addition of a TTO when
      performing a medial opening wedge HTO minimizes the decreases in patellar height
      associated with the procedure.

PMID- 24077134
TI  - RCVS invites voluntary disclosure of criminal convictions.

PMID- 24077133
TI  - FAO, OIE and WHO issue joint statement on rabies.

PMID- 24077131
TI  - Update on the neurobiology of schizophrenia: a role for extracellular
      microdomains.
AB  - The glutamate system includes presynaptic glutamatergic terminals, complex post
      synaptic densities found on diverse types of neurons expressing glutamate
      receptors, as well as glutamate transporters and enzymes that facilitate the
      glutamate/glutamine cycle. Abnormalities of this system have been implicated in
      schizophrenia based on an accumulating body of evidence from postmortem, imaging,
      and preclinical studies. However, recent work has suggested that astrocytes may
      have more than a bystander role in the synchronization of neuronal responses in
      the brain. Converging evidence suggests that extrasynaptic glutamate microdomains
      are formed by astrocytes and may facilitate neuroplasticity via the modulation of
      extra-synaptic glutamate receptors on neuronal membranes within these domains. In
      this article the authors propose that the composition and localization of protein
      complexes in glutamate microdomains is abnormal in schizophrenia, leading to
      pathological neuroplastic changes in the structure and function of glutamate
      circuits in this illness.

PMID- 24077136
TI  - Salaries survey brings 'sobering news' for vets in small animal practice.

PMID- 24077135
TI  - Target in sight for Mission Rabies.

PMID- 24077138
TI  - Limited response to FOI requests on badger cull.

PMID- 24077139
TI  - A career devoted to improving welfare.

PMID- 24077143
TI  - Disciplinary case adjourned after vet removes himself from the Register.

PMID- 24077144
TI  - The big problem: battling companion animal obesity.

PMID- 24077145
TI  - Not small horses: improving treatments for donkeys.

PMID- 24077146
TI  - Small-scale flock seroprevalence study indicates incomplete natural protection
      against SBV.

PMID- 24077147
TI  - Ear droop and stertor in dairy calves associated with Mycoplasma bovis.

PMID- 24077148
TI  - Thrombotic thrombocytopenic purpura and cardiac papillary fibroelastoma: a
      'unique coexistence'.
AB  - Thrombotic thrombocytopenic purpura (TTP), a complex thrombotic microangiopathy,
      remains an evolving enigma. A 49-year-old African-American woman presented with
      acute left hemiplegia, an ischemic cerebrovascular accident involving the right
      middle cerebral artery. Sequential appearance of thrombocytopenia and evidence of
      microangiopathic haemolysis led to the diagnosis of acquired idiopathic
      autoimmune TTP. This was managed with plasma exchange (PEX) and steroids. Early
      haematologic relapse within a month was managed with the addition of rituximab
      attaining sustained remission. The patient presented 3 years later with acute
      confusion and expressive aphasia due to multiple infarcts involving the left
      parieto-occipital cortex. Transoesophageal echocardiography demonstrated a
      pedunculated 6 mm mitral valvular mass consistent with a papillary fibroelastoma.
      Anticoagulation was instituted and the patient was continued on therapeutic oral
      warfarin. A haematologic relapse of TTP eventually emerged and was managed with
      PEX, steroids and rituximab. This vignette demonstrates several dilemmas in the
      clinical presentation, diagnosis and management of TTP in current day practice.
      Rituximab has adjuvant benefits to PEX and is being investigated as potential
      first-line therapy. Monitoring ADAMTS13 activity and inhibitor titre, as in our
      case, prove to have prognostic significance. Cardiac fibroelastomas are rare
      benign cardiac tumours usually arising from valvular endocardium with
      thromboembolic potential. One of the proposed mechanisms of origin of these
      masses is organizing thrombi in the setting of endocardial injury and
      inflammation questioning a possible link to thrombotic microangiopathy. To the
      best of our knowledge, this is the first report of this unique coexistence. 

PMID- 24077149
TI  - Hydrothermal pretreatment of bamboo and cellulose degradation.
AB  - A systematic hydrothermal pretreatment of bamboo chips had been conducted with an
      aim to trace the cellulose degradation. The results showed that cellulose chain
      cleavage basically occurred when the temperature exceeded 150 degrees C. A
      slightly higher DP (degree of polymerization) than starting material had been
      observed at low temperature pretreatment. Treatment at higher temperature (>= 170
      degrees C) caused severe cleavage of cellulose and therefore gave rise to low DP
      with more soluble species. DP of cellulose declined drastically without
      additional hemicelluloses dissolution when hemicelluloses removal reached to the
      limit level. Cellulose degradation under hydrothermal pretreatment generally
      followed the zero reaction kinetics with the activity energy of 121.0 kJ/mol.
      Besides, the increase of cellulose crystalline index and the conversion of Ialpha
      Ibeta had also observed at the hydrothermal pretreatment.

PMID- 24077150
TI  - The adsorption behavior and mechanism investigation of Pb(II) removal by
      flocculation using microbial flocculant GA1.
AB  - In this work, microbial flocculant GA1 (MBFGA1) was used to remove Pb(II) ions
      from aqueous solution. A series of experimental parameters including initial pH,
      MBFGA1 dose, temperature and initial calcium ions concentration on Pb(II) uptake
      was evaluated. Meanwhile, the flocculation mechanism of MBFGA1 was investigated.
      The removal efficiency of Pb(II) reached up to 99.85% when MBFGA1 was added in
      two stages, separately. The results indicated that Pb(II) adsorption could be
      described by the Langmuir adsorption model, and being the monolayer capacity
      negatively affected with an increase in temperature. The adsorption process could
      be described by pseudo-second-order kinetic model. Fourier transform-infrared
      spectra and environmental scanning electron microscope analysis indicated that
      MBFGA1 had a large number of functional groups, which had strong capacity for
      removing Pb(II). The main mechanisms of Pb(II) removal by MBFGA1 could be charge
      neutralization and adsorption bridging. 

PMID- 24077151
TI  - Integration of a phenolic-acid recovery step in the CaCCO process for efficient
      fermentable-sugar recovery from rice straw.
AB  - An advanced sugar-platform bioprocess for lignocellulosic feedstocks by adding a
      phenolic-acid (PA: p-coumaric acid and ferulic acid) recovery step to the CaCCO
      process was designed. For efficient PA extraction, pretreatment was 95 degrees C
      for 2h, producing a yield of 7.30 g/kg-dry rice straw (65.2% of total ester
      linked PAs) with insignificant effects on saccharification. PAs were readily
      recovered in solution during the repeated washings of solids, and the glucose
      yield, after 72-h saccharification of the washed solids, was significantly
      improved from 65.9% to 70.3-72.7%, suggesting the removal of potential enzyme
      inhibitors. The promotion of xylose yield was insignificant, probably due to 13.1
      17.8% loss of xylose residues after washing(s). This new bioprocess, termed the
      SRB (simultaneous recovery of by-products)-CaCCO process, would effectively
      produce fermentable sugars and other valuables from feedstocks, strengthening the
      platform in both economic and environmental terms.

PMID- 24077152
TI  - The characteristics of extracellular polymeric substances and soluble microbial
      products in moving bed biofilm reactor-membrane bioreactor.
AB  - The characteristics of extracellular polymeric substances (EPS) and soluble
      microbial products (SMP) in conventional membrane bioreactor (MBR) and in moving
      bed biofilm reactor-membrane bioreactors (MBBR-MBR) were investigated in long
      term (170 days) experiments. The results showed that all reactors had high
      removal efficiency of ammonium and COD, despite very different fouling
      conditions. The MBBR-MBR with media fill ratio of 26.7% had much lower total
      membrane resistance and no obvious fouling were detected during the whole
      operation. In contrast, MBR and MBBR-MBR with lower and higher media fill
      experienced more significant fouling. Low fouling at optimum fill ratio may be
      due to the higher percentage of small molecular size (<1 kDa) and lower
      percentage of large molecular size (>100 kDa) of EPS and SMP in the reactor. The
      composition of EPS and SMP affected fouling due to different O-H bonds in
      hydroxyl functional groups, and less polysaccharides and lipids.

PMID- 24077153
TI  - Optimisation of the two-phase dry-thermophilic anaerobic digestion process of
      sulphate-containing municipal solid waste: population dynamics.
AB  - Microbial population dynamics and anaerobic digestion (AD) process to eight
      different hydraulic retention times (HRTs) (from 25d to 3.5d) in two-phase dry
      thermophilic AD from sulphate-containing solid waste were investigated. Maximum
      values of gas production (1.9 +/- 0.2 l H2/l/d; 5.4 +/- 0.3 l CH4/l/d and 82 +/-
      9 ml H2S/l/d) and microbial activities were obtained at 4.5d HRT; where basically
      comprised hydrolysis step in the first phase (HRT=1.5d) and acidogenic step
      finished in the second phase as well as acetogenic-methanogenic steps (HRT=3d).
      In the first phase, hydrolytic-acidogenic bacteria (HABs) was the main group (44
      77%) and Archaea, acetogens and sulphate-reducing bacteria (SRBs) contents were
      not significant; in the second phase (except to 2d HRT), microbial population was
      able to adapt to change in substrate and HRTs to ensure the proper functioning of
      the system and both acetogens and Archaea were dominated over SRBs. Decreasing
      HRT resulted in an increase in microbial activities.

PMID- 24077154
TI  - Establishment and assessment of a novel cleaner production process of corn grain
      fuel ethanol.
AB  - An integrated corn ethanol-methane fermentation system was proposed to solve the
      problem of stillage handling, where thin stillage was treated by anaerobic
      digestion and then reused to make mash for the following ethanol fermentation.
      This system was evaluated at laboratory and pilot scale. Anaerobic digestion of
      thin stillage ran steadily with total chemical oxygen demand removal efficiency
      of 98% at laboratory scale and 97% at pilot scale. Ethanol production was not
      influenced by recycling anaerobic digestion effluent at laboratory and pilot
      scale. Compared with dried distillers' grains with solubles produced in
      conventional process, dried distillers' grains in the proposed system exhibited
      higher quality because of increased protein concentration and decreased salts
      concentration. Energetic assessment indicated that application of this novel
      process enhanced the net energy balance ratio from 1.26 (conventional process) to
      1.76. In conclusion, the proposed system possessed technical advantage over the
      conventional process for corn fuel ethanol production. 

PMID- 24077155
TI  - Hydrolysis and acidification of dewatered sludge under mesophilic, thermophilic
      and extreme thermophilic conditions: effect of pH.
AB  - This study investigated the effect of pH (uncontrolled, 8.0, 10.0 and 12.0) and
      temperature (mesophilic, thermophilic and extreme thermophilic) on hydrolysis and
      acidification of dewatered sludge in 7-day batch fermentation experiment.
      Solublization of COD, protein and carbohydrates as well as concentration and
      composition of VFAs were investigated. Sludge hydrolysis was enhanced with higher
      pH and temperature. The maximum SCOD, soluble protein and carbohydrates was
      observed at pH 12.0 at extreme thermophilic condition. The maximum VFAs yield was
      obtained at thermophilic and was 2.15 times that at mesophilic condition, but it
      took more time to reach the maximum. The VFAs consisted of acetic, propionic, iso
      butyric, n-butyric, iso-valeric, and n-valeric acids, and acetic acid was the
      prevalent product in most cases except for uncontrolled pH and pH 8.0 at
      mesophilic condition. The methane production was as follows: pH 8.0>pH
      10.0>uncontrolled (0.015)>pH 12.0; mesophilic>thermophilic>extreme thermophilic. 

PMID- 24077156
TI  - Start-up of the completely autotrophic nitrogen removal process using low
      activity anammox inoculum to treat low strength UASB effluent.
AB  - The start-up of the completely autotrophic nitrogen removal process was examined
      in a sequencing batch reactor (SBR) using low activity anoxic ammonium oxidation
      (anammox) inoculum. The SBR received effluent from an upflow anaerobic sludge
      blanket (UASB) that treated low strength wastewater. The volumetric nitrogen
      loading rate (vNLR) was first 0.24 +/- 0.11 kg Nm(-3)d(-1) and then reduced to
      0.10 +/- 0.02 kg Nm(-3)d(-1). The average specific anammox activity was 2.27 +/-
      1.31 mg N (gVSS h)(-1), at 30 degrees C representing an increase of 161% compared
      to the inoculum. The decrease in vNLR did not significantly affect anammox
      activity, but resulted in a decrease of denitrifying heterotrophic activity to
      very low levels after the first 30 days owing to the decrease of organic loading
      rate (OLR). Fluorescence in situ hybridization (FISH) analysis confirmed the
      stable presence of anammox bacteria in biomass. Numerous filamentous
      microorganisms were present, several of which were in a state of endogenous
      respiration.

PMID- 24077157
TI  - Effect of dark/light periods on the polyhydroxyalkanoate production of a
      photosynthetic mixed culture.
AB  - This work studied the possibility of operating a viable polyhydroxyalkanoate
      (PHA) producing photosynthetic mixed culture (PMC) under dark/light periods
      without aeration. The culture was subjected to a feast and famine regime, being
      fed in the dark phase and entering into famine during the light phase. Throughout
      consecutive feast and famine dark/light periods, the PMC became enriched in PHA
      accumulating organisms, where non-PHA producing algae that can grow under
      continuous illumination were out-competed. The very low algae levels enabled
      greater light and carbon source availability for PHA accumulating bacteria,
      leading to higher metabolic rates and PHA levels. The PMC reached a PHA content
      of 30% PHA/VSS, and doubled its specific PHA production rate in relation to PMCs
      operated previously under continuous illumination. This new process takes a
      further step towards operating a more cost effective PMC system for PHA
      production, opening up the possibility for direct sunlight utilization in the
      future. 

PMID- 24077158
TI  - Comparing the short and long term stability of biodegradable, ceramic and cation
      exchange membranes in microbial fuel cells.
AB  - The long and short-term stability of two porous dependent ion exchange materials;
      starch-based compostable bags (BioBag) and ceramic, were compared to commercially
      available cation exchange membrane (CEM) in microbial fuel cells. Using bi
      directional polarisation methods, CEM exhibited power overshoot during the
      forward sweep followed by significant power decline over the reverse sweep (38%).
      The porous membranes displayed no power overshoot with comparably smaller drops
      in power during the reverse sweep (ceramic 8%, BioBag 5.5%). The total internal
      resistance at maximum power increased by 64% for CEM compared to 4% (ceramic) and
      6% (BioBag). Under fixed external resistive loads, CEM exhibited steeper pH
      reductions than the porous membranes. Despite its limited lifetime, the BioBag
      proved an efficient material for a stable microbial environment until failing
      after 8 months, due to natural degradation. These findings highlight porous
      separators as ideal candidates for advancing MFC technology in terms of cost and
      operation stability. 

PMID- 24077159
TI  - Lipid-enhancement of activated sludges obtained from conventional activated
      sludge and oxidation ditch processes.
AB  - Lipid-enhancement of activated sludges was conducted to increase the amount of
      saponifiable lipids in the sludges. The sludges were obtained from a conventional
      activated sludge (CAS) and an oxidation ditch process (ODP). Results showed 59
      222% and 150-250% increase in saponifiable lipid content of the sludges from CAS
      and ODP, respectively. The fatty acid methyl ester (FAMEs) obtained from
      triacylglycerides was 57-67% (of total FAMEs) for enhanced CAS and 55-73% for
      enhanced ODP, a very significant improvement from 6% to 10% (CAS) and 4% to 8%
      (ODP). Regardless of the source, the enhancement resulted in sludges with similar
      fatty acid profile indicating homogenization of the lipids in the sludges. This
      study provides a potential strategy to utilize existing wastewater treatment
      facilities as source of significant amount of lipids for biofuel applications. 

PMID- 24077160
TI  - [Vasculitis 2013. What are the changes introduced in the 2012 Chapel Hill
      Consensus Conference?].
AB  - Vasculitis is a heterogeneous group of rare disorders in which inflammation of
      blood vessels is the common feature. Due to the increasing number of diseases as
      well as overlaps and gaps in the definition and nomenclature, the classification
      criteria were constantly changing in the past decades. The classifications were
      based essentially on the size of affected blood vessels and pathologic
      characteristics of inflamed vessel walls. The standard procedures and validated
      diagnostic criteria are missing from the diagnostics of vasculitis, thus in
      clinical practice the classification criteria are applicable. The 2012 Chapel
      Hill Consensus Conference brought a change in the definition, nomenclature and
      classification of previously uncategorized diseases. The definitions of subgroups
      accurately determine the diagnosis of the specific disease, and they are suitable
      for establishing homogeneous disease groups. By better understanding of the
      etiopathogenetic factors, further diseases and subgroups may be defined in the
      near future.

PMID- 24077161
TI  - [Hungarian twin studies: results of four decades].
AB  - Twin studies play a role in examining the contribution of genetic variations and
      environmental factors responsible for the determination of phenotypic variables
      and of genetic linkage between genotypes. Hungarian twin studies, supported by
      three twin registries (among them two twin-database), date back to 1970s. Studies
      mainly focused on various congenital abnormalities, the effect of contraceptive
      pills and folic acid on the frequency of twin pregnancies, as well as
      psychosexual and alcohol consumptional behaviors. Monogenic Mendelian inheritance
      of lactose (mal)absorption was demonstrated for the first time. Hungarian Twin
      Registry was founded in 2007, which contributed to the current understanding on
      the background of several disorders, e.g. metabolic syndrome and atherosclerosis.
      As part of an international twin study, among others, arterial stiffness, central
      blood pressure, carotid intima/media thickness, venous biomechanics, body
      composition, lung function and smoking characteristics were also assessed.
      Absence of genetic background in non-alcoholic fatty liver disease and high
      inheritance of carotid plaque characteristics were demonstrated for the first
      time. The review also aims to summarize future plans of the Hungarian Twin
      Registry.

PMID- 24077162
TI  - [Patient adherence in antihypertensive treatment].
AB  - Hypertension is one of the most frequent chronic diseases as well as most
      important cardiovascular risk factors in developed countries. Blood pressure
      control to target levels can significantly decrease the risk for development of
      coronary artery disease, stroke, chronic renal disease and mortality. Adequately
      maintained blood pressure is very important in high risk patients. In the
      treatment of hypertension, life style therapy and drug treatment have essential
      roles. Further, patient adherence plays a significant part of the treatment, too.
      Importantly, about half of the patients only become adherent to antihypertensive
      therapy by the end of the first year treatment. Hence, non-adherence of patients
      is an important cause for resistant hypertension. Adherence is influenced by the
      complexity of drug regimen and characteristic of drug class, as well as age and
      gender of patients.

PMID- 24077163
TI  - [Sleep duration among school-age children in Hungary and Romania].
AB  - INTRODUCTION: Children's sleep duration is decreasing in the last decade. Despite
      of the well known negative consequences, there are no data on children's sleep
      duration in Hungary and Romania. AIM: The aim of the authors was to assess sleep
      duration of school-age children in Hungary and Romania. METHOD: A self-edited
      questionnaire was used for the study. 2446 children were enrolled. All elementary
      and secondary schools in a Hungarian city, and one elementary and secondary
      school in a Romanian city took part in the study. RESULTS: Mean sleep duration
      was 8.3 +/- 1.2 hours on weekdays. There was a significant difference between the
      two countries (Hungary vs. Romania, 8.5 +/- 1.2 hours vs. 7.8 +/- 0.9 hours, p =
      0.001). Age correlated with sleep duration on weekdays (r= -0.605, p = 0.001),
      but not during weekend. CONCLUSIONS: This is the first study on children's sleep
      duration in Hungary and Romania. The difference between countries may be due to
      the difference in mean age or cultural and/or geographical differences.

PMID- 24077164
TI  - [Prof. dr. Magdolna Zajacz (1932-2013)].

PMID- 24077165
TI  - [The Bible -- a medical approach. VIII. Goliath syndrome: does it exist? Eye
      diseases in the Bible].

PMID- 24077166
TI  - [To the Editors regarding S. Magony et al., "In the labyrinth of calcium
      metabolism"].

PMID- 24077167
TI  - Ten-eleven translocation-2 (TET2) is a master regulator of smooth muscle cell
      plasticity.
AB  - BACKGROUND: Smooth muscle cells (SMCs) are remarkably plastic. Their reversible
      differentiation is required for growth and wound healing but also contributes to
      pathologies such as atherosclerosis and restenosis. Although key regulators of
      the SMC phenotype, including myocardin (MYOCD) and KLF4, have been identified, a
      unifying epigenetic mechanism that confers reversible SMC differentiation has not
      been reported. METHODS AND RESULTS: Using human SMCs, human arterial tissue, and
      mouse models, we report that SMC plasticity is governed by the DNA-modifying
      enzyme ten-eleven translocation-2 (TET2). TET2 and its product, 5
      hydroxymethylcytosine (5-hmC), are enriched in contractile SMCs but reduced in
      dedifferentiated SMCs. TET2 knockdown inhibits expression of key procontractile
      genes, including MYOCD and SRF, with concomitant transcriptional upregulation of
      KLF4. TET2 knockdown prevents rapamycin-induced SMC differentiation, whereas TET2
      overexpression is sufficient to induce a contractile phenotype. TET2
      overexpression also induces SMC gene expression in fibroblasts. Chromatin
      immunoprecipitation demonstrates that TET2 coordinately regulates phenotypic
      modulation through opposing effects on chromatin accessibility at the promoters
      of procontractile versus dedifferentiation-associated genes. Notably, we find
      that TET2 binds and 5-hmC is enriched in CArG-rich regions of active SMC
      contractile promoters (MYOCD, SRF, and MYH11). Loss of TET2 and 5-hmC positively
      correlates with the degree of injury in murine models of vascular injury and
      human atherosclerotic disease. Importantly, localized TET2 knockdown exacerbates
      injury response, and local TET2 overexpression restores the 5-hmC epigenetic
      landscape and contractile gene expression and greatly attenuates intimal
      hyperplasia in vivo. CONCLUSIONS: We identify TET2 as a novel and necessary
      master epigenetic regulator of SMC differentiation.

PMID- 24077168
TI  - UnTEThering (smooth muscle) cell plasticity.

PMID- 24077169
TI  - Association of low-grade albuminuria with adverse cardiac mechanics: findings
      from the hypertension genetic epidemiology network (HyperGEN) study.
AB  - BACKGROUND: Albuminuria is a marker of endothelial dysfunction and has been
      associated with adverse cardiovascular outcomes. The reasons for this association
      are unclear but may be attributable to the relationship between endothelial
      dysfunction and intrinsic myocardial dysfunction. METHODS AND RESULTS: In the
      Hypertension Genetic Epidemiology Network (HyperGEN) Study, a population- and
      family-based study of hypertension, we examined the relationship between urine
      albumin-to-creatinine ratio (UACR) and cardiac mechanics (n=1894, all of whom had
      normal left ventricular ejection fraction and wall motion). We performed speckle
      tracking echocardiographic analysis to quantify global longitudinal,
      circumferential, and radial strain, and early diastolic (e') tissue velocities.
      We used E/e' ratio as a marker of increased left ventricular filling pressures.
      We used multivariable-adjusted linear mixed effect models to determine
      independent associations between UACR and cardiac mechanics. The mean age was
      50+/-14 years, 59% were female, and 46% were black. Comorbidities were
      increasingly prevalent among higher UACR quartiles. Albuminuria was associated
      with global longitudinal strain, global circumferential strain, global radial
      strain, e' velocity, and E/e' ratio on unadjusted analyses. After adjustment for
      covariates, UACR was independently associated with lower absolute global
      longitudinal strain (multivariable-adjusted mean global longitudinal strain [95%
      confidence interval] for UACR Quartile 1 = 15.3 [15.0-15.5]% versus UACR Q4 =
      14.6 [14.3-14.9]%, P for trend <0.001) and increased E/e' ratio (Q1 = 25.3 [23.5
      27.1] versus Q4 = 29.0 [27.0-31.0], P=0.003). The association between UACR and
      global longitudinal strain was present even in participants with UACR < 30 mg/g
      (P<0.001 after multivariable adjustment). CONCLUSIONS: Albuminuria, even at low
      levels, is associated with adverse cardiac mechanics and higher E/e' ratio.

PMID- 24077170
TI  - Inaccuracy of estimated resting oxygen uptake in the clinical setting.
AB  - BACKGROUND: The Fick principle (cardiac output = oxygen uptake ( O2)/systemic
      arterio-venous oxygen difference) is used to determine cardiac output in numerous
      clinical situations. However, estimated rather than measured O2 is commonly used
      because of complexities of the measurement, though the accuracy of estimation
      remains uncertain in contemporary clinical practice. METHODS AND RESULTS: From
      1996 to 2005, resting O2 was measured via the Douglas bag technique in adult
      patients undergoing right heart catheterization. Resting O2 was estimated by each
      of 3 published formulae. Agreement between measured and estimated O2 was assessed
      overall, and across strata of body mass index, sex, and age. The study included
      535 patients, with mean age 55 yrs, mean body mass index 28.4 kg/m2; 53% women;
      64% non-white. Mean (+/-standard deviation) measured O2 was 241 +/- 57 ml/min.
      Measured O2 differed significantly from values derived from all 3 formulae, with
      median (interquartile range) absolute differences of 28.4 (13.1, 50.2) ml/min,
      37.7 (19.4, 63.3) ml/min, and 31.7 (14.4, 54.5) ml/min, for the formulae of
      Dehmer, LaFarge, and Bergstra, respectively (P<0.0001 for each). The measured and
      estimated values differed by >25% in 17% to 25% of patients depending on the
      formula used. Median absolute differences were greater in severely obese patients
      (body mass index > 40 kg/m2), but were not affected by sex or age. CONCLUSIONS:
      Estimates of resting O2 derived from conventional formulae are inaccurate,
      especially in severely obese individuals. When accurate hemodynamic assessment is
      important for clinical decision-making, O2 should be directly measured.

PMID- 24077171
TI  - Two new monoterpenes from the fruits of Illicium lanceolatum.
AB  - Two new monoterpenes, p-mentha-1(7),8-dien-2-O-beta-D-glucoside and trans-2,4
      dihydroxy-2,4-dimethyl-trans-1-acetic acid gamma-lactone were isolated from the
      fruits of Illicium lanceolatum along with trans-2,4-dihydroxy-2,4-dimethyl-cis-1
      acetic acid gamma-lactone, (1R,2R,4R)-8-p-menthen-1,2-diol, trans-sobrerol,
      (1S,2S,4R)-p-menthane-1,2,8-triol and (1S, 2S, 4R, 8R)-p-menthane-1,2,9-triol.
      The structures of the isolates were confirmed by spectroscopic analysis and they
      showed no inhibitory effects on the in vitro growth of microbial organisms
      (Escherichia coli, Staphyloccocus aureus, Bacillus subtilis) at less than 1.0
      mg/mL.

PMID- 24077172
TI  - Nuclear magnetic resonance approaches in the study of 2-oxo acid dehydrogenase
      multienzyme complexes--a literature review.
AB  - The 2-oxoacid dehydrogenase complexes (ODHc) consist of multiple copies of three
      enzyme components: E1, a 2-oxoacid decarboxylase; E2, dihydrolipoyl acyl
      transferase; and E3, dihydrolipoyl dehydrogenase, that together catalyze the
      oxidative decarboxylation of 2-oxoacids, in the presence of thiamin diphosphate
      (ThDP), coenzyme A (CoA), Mg2+ and NAD+, to generate CO2, NADH and the
      corresponding acyl-CoA. The structural scaffold of the complex is provided by E2,
      with E1 and E3 bound around the periphery. The three principal members of the
      family are pyruvate dehydrogenase (PDHc), 2-oxoglutarate dehydrogenase (OGDHc)
      and branched-chain 2-oxo acid dehydrogenase (BCKDHc). In this review, we report
      application of NMR-based approaches to both mechanistic and structural issues
      concerning these complexes. These studies revealed the nature and reactivity of
      transient intermediates on the enzymatic pathway and provided site-specific
      information on the architecture and binding specificity of the domain interfaces
      using solubilized truncated domain constructs of the multi-domain E2 component in
      its interactions with the E1 and E3 components. Where studied, NMR has also
      provided information about mobile loops and the possible relationship of mobility
      and catalysis.

PMID- 24077173
TI  - Measuring dynamic and kinetic information in the previously inaccessible supra
      tau(c) window of nanoseconds to microseconds by solution NMR spectroscopy.
AB  - Nuclear Magnetic Resonance (NMR) spectroscopy is a powerful tool that has enabled
      experimentalists to characterize molecular dynamics and kinetics spanning a wide
      range of time-scales from picoseconds to days. This review focuses on addressing
      the previously inaccessible supra-tc window (defined as tau(c) < supra-tau(c) <
      40 MUs; in which tc is the overall tumbling time of a molecule) from the
      perspective of local inter-nuclear vector dynamics extracted from residual
      dipolar couplings (RDCs) and from the perspective of conformational exchange
      captured by relaxation dispersion measurements (RD). The goal of the first
      section is to present a detailed analysis of how to extract protein dynamics
      encoded in RDCs and how to relate this information to protein functionality
      within the previously inaccessible supra-tau(c) window. In the second section,
      the current state of the art for RD is analyzed, as well as the considerable
      progress toward pushing the sensitivity of RD further into the supra-tau(c) scale
      by up to a factor of two (motion up to 25 MUs). From the data obtained with these
      techniques and methodology, the importance of the supra-tau(c) scale for protein
      function and molecular recognition is becoming increasingly clearer as the
      connection between motion on the supra-tau(c) scale and protein functionality
      from the experimental side is further strengthened with results from molecular
      dynamics simulations.

PMID- 24077175
TI  - An efficient solvent-free synthesis of 2-hydroxy-2-(trifluoromethyl)-2H-chromenes
      using silica-immobilized L-proline.
AB  - An efficient synthesis of 2-hydroxy-2-(trifluoromethyl)-2H-chromene-3
      carboxylates was carried out under solvent-free conditions in an oven or
      microwave oven via the Knoevenagel condensation of salicylaldehydes with ethyl
      trifluoroacetoacetate followed by intramolecular cyclization in the presence of
      silica-immobilized L-proline. The structures of the title compounds were
      characterized by IR, 1H-NMR, 13C-NMR, HRMS and X-ray single crystal diffraction.
      The improved method described herein is economical, easily-operated and
      environmentally friendly. Furthermore, the catalyst can be recovered conveniently
      and reused without obvious loss of activity.

PMID- 24077174
TI  - Macrocyclic pyridyl polyoxazoles: structure-activity studies of the aminoalkyl
      side-chain on G-quadruplex stabilization and cytotoxic activity.
AB  - Pyridyl polyoxazoles are 24-membered macrocyclic lactams comprised of a pyridine,
      four oxazoles and a phenyl ring. A derivative having a 2-(dimethylamino)ethyl
      chain attached to the 5-position of the phenyl ring was recently identified as a
      selective G-quadruplex stabilizer with excellent cytotoxic activity, and good in
      vivo anticancer activity against a human breast cancer xenograft in mice. Here we
      detail the synthesis of eight new dimethylamino-substituted pyridyl polyoxazoles
      in which the point of attachment to the macrocycle, as well as the distance
      between the amine and the macrocycle are varied. Each compound was evaluated for
      selective G-quadruplex stabilization and cytotoxic activity. The more active
      analogs have the amine either directly attached to, or separated from the phenyl
      ring by two methylene groups. There is a correlation between those macrocycles
      that are effective ligands for the stabilization of G-quadruplex DNA (DT(tran)
      15.5-24.6  degrees C) and cytotoxicity as observed in the human tumor cell lines,
      RPMI 8402 (IC50 0.06-0.50 MUM) and KB3-1 (IC50 0.03-0.07 MUM). These are highly
      selective G-quadruplex stabilizers, which should prove especially useful for
      evaluating both in vitro and in vivo mechanism(s) of biological activity
      associated with G-quaqdruplex ligands.

PMID- 24077176
TI  - Synthesis and antibacterial evaluation of some novel imidazole and benzimidazole
      sulfonamides.
AB  - Several new substituted sulfonamide compounds were synthesized and their
      structures were confirmed by 1H-NMR, 13C-NMR, FT-IR, and mass spectroscopy. The
      antibacterial activities of the synthesized compounds were screened against
      standard strains of six Gram positive and four Gram negative bacteria using the
      microbroth dilution assay. Most of the compounds studied showed promising
      activities against both types of bacteria.

PMID- 24077177
TI  - Structural correlation of some heterocyclic chalcone analogues and evaluation of
      their antioxidant potential.
AB  - A series of six novel heterocyclic chalcone analogues 4(a-f) has been synthesized
      by condensing 2-acetyl-5-chlorothiophene with benzaldehyde derivatives in
      methanol at room temperature using a catalytic amount of sodium hydroxide. The
      newly synthesized compounds are characterized by IR, mass spectra, elemental
      analysis and melting point. Subsequently; the structures of these compounds were
      determined using single crystal X-ray diffraction. All the synthesized compounds
      were screened for their antioxidant potential by employing various in vitro
      models such as DPPH free radical scavenging assay, ABTS radical scavenging assay,
      ferric reducing antioxidant power and cupric ion reducing antioxidant capacity.
      Results reflect the structural impact on the antioxidant ability of the
      compounds. The IC0 values illustrate the mild to good antioxidant activities of
      the reported compounds. Among them, 4f with a p-methoxy substituent was found to
      be more potent as antioxidant agent.

PMID- 24077178
TI  - Role of sirtuins in lifespan regulation is linked to methylation of nicotinamide.
AB  - Sirtuins, a family of histone deacetylases, have a fiercely debated role in
      regulating lifespan. In contrast with recent observations, here we find that
      overexpression of sir-2.1, the ortholog of mammalian SirT1, does extend
      Caenorhabditis elegans lifespan. Sirtuins mandatorily convert NAD(+) into
      nicotinamide (NAM). We here find that NAM and its metabolite, 1
      methylnicotinamide (MNA), extend C. elegans lifespan, even in the absence of sir
      2.1. We identify a previously unknown C. elegans nicotinamide-N
      methyltransferase, encoded by a gene now named anmt-1, to generate MNA from NAM.
      Disruption and overexpression of anmt-1 have opposing effects on lifespan
      independent of sirtuins, with loss of anmt-1 fully inhibiting sir-2.1-mediated
      lifespan extension. MNA serves as a substrate for a newly identified aldehyde
      oxidase, GAD-3, to generate hydrogen peroxide, which acts as a mitohormetic
      reactive oxygen species signal to promote C. elegans longevity. Taken together,
      sirtuin-mediated lifespan extension depends on methylation of NAM, providing an
      unexpected mechanistic role for sirtuins beyond histone deacetylation. 

PMID- 24077179
TI  - Small molecules intercept Notch signaling and the early secretory pathway.
AB  - Notch signaling has a pivotal role in numerous cell-fate decisions, and its
      aberrant activity leads to developmental disorders and cancer. To identify
      molecules that influence Notch signaling, we screened nearly 17,000 compounds
      using automated microscopy to monitor the trafficking and processing of a ligand
      independent Notch-enhanced GFP (eGFP) reporter. Characterization of hits in vitro
      by biochemical and cellular assays and in vivo using zebrafish led to five
      validated compounds, four of which induced accumulation of the reporter at the
      plasma membrane by inhibiting gamma-secretase. One compound, the dihydropyridine
      FLI-06, disrupted the Golgi apparatus in a manner distinct from that of brefeldin
      A and golgicide A. FLI-06 inhibited general secretion at a step before exit from
      the endoplasmic reticulum (ER), which was accompanied by a tubule-to-sheet
      morphological transition of the ER, rendering FLI-06 the first small molecule
      acting at such an early stage in secretory traffic. These data highlight the
      power of phenotypic screening to enable investigations of central cellular
      signaling pathways. 

PMID- 24077180
TI  - Mycobacterium tuberculosis nitrogen assimilation and host colonization require
      aspartate.
AB  - Here we identify the amino acid transporter AnsP1 as the unique aspartate
      importer in the human pathogen Mycobacterium tuberculosis. Metabolomic analysis
      of a mutant with an inactive AnsP1 revealed that the transporter is essential for
      M. tuberculosis to assimilate nitrogen from aspartate. Virulence of the AnsP1
      mutant is impaired in vivo, revealing that aspartate is a primary nitrogen source
      required for host colonization by the tuberculosis bacillus. 

PMID- 24077181
TI  - Effect of CPAP on blood pressure in patients with OSA/hypopnea a systematic
      review and meta-analysis.
AB  - BACKGROUND: CPAP is considered the therapy of choice for OSA, but the extent to
      which it can reduce BP is still under debate. We undertook a systematic review
      and meta-analysis of randomized controlled trials (RCTs) to quantify the effect
      size of the reduction of BP by CPAP therapy compared with other passive (sham
      CPAP, tablets of placebo drug, conservative measures) or active (oral appliance,
      antihypertensive drugs) treatments. METHODS: We searched four different databases
      (MEDLINE, EMBASE, Web of Science, and the Cochrane Library) with specific search
      terms and selection criteria. RESULTS: From 1,599 articles, we included 31 RCTs
      that compared CPAP with either passive or active treatment. In a random-effects
      meta-analysis vs passive treatment (29 RCTs, 1,820 subjects), we observed a
      mean+/-SEM net difference in systolic BP of 2.6+/-0.6 mm Hg and in diastolic BP
      of 2.0+/-0.4 mm Hg, favoring treatment with CPAP (P<.001). Among studies using 24
      h ambulatory BP monitoring that presented data on daytime and nighttime periods,
      the mean difference in systolic and diastolic BP was, respectively, 2.2+/-0.7 and
      1.9+/-0.6 mm Hg during daytime and 3.8+/-0.8 and 1.8+/-0.6 mm Hg during
      nighttime. In meta-regression analysis, a higher baseline apnea/hypopnea index
      was associated with a greater mean net decrease in systolic BP (beta+/-SE, 0.08+/
      0.04). There was no evidence of publication bias, and heterogeneity was mild (
      I2, 34%-36%). CONCLUSIONS: Therapy with CPAP significantly reduces BP in patients
      with OSA but with a low effect size. Patients with frequent apneic episodes may
      benefit the most from CPAP.

PMID- 24077182
TI  - A novel [1,2,4] triazolo [1,5-a] pyrimidine-based phenyl-linked steroid dimer:
      synthesis and its cytotoxic activity.
AB  - A novel [1,2,4] triazolo [1,5-a] pyrimidine-based phenyl-linked steroid dimer was
      designed, synthesized and evaluated for its cytotoxic activity against five human
      cancer cell lines and the cytotoxicity against human normal liver cell L-02.
      Compound 3 showed excellent cytotoxic activity and good selectivity between
      cancer and normal cells. Further mechanistic studies revealed that treatment of
      EC109 cells with compound 3 caused an obvious G2/M arrest in a concentration- and
      time-dependent manner and induced apoptosis probably through the mitochondrial
      pathway accompanied with the decrease of mitochondrial membrane potential,
      activations of caspase-9/-3, cleavage of MDM2 as well as up-regulation of the
      expressions of p53 and Bax. 

PMID- 24077184
TI  - Waterborne cadmium impacts immunocytotoxic and cytogenotoxic endpoints in green
      lipped mussel, Perna canaliculus.
AB  - Mussels are sentinel species that can be used to monitor coastal metal pollution
      through the application of biomarkers. Among the several important metal
      toxicants in coastal settings, cadmium (Cd) is of particular concern, being a non
      essential metal that is known to cause harmful impacts in aquatic organisms at
      low concentrations. The aim of the present study was to examine the
      immunocytotoxic and cytogenotoxic effects of Cd on the green-lipped mussel, Perna
      canaliculus, under laboratory conditions. The acute (96 h; 0, 2000 and 4000 MUg
      Cd L(-1)) and subchronic (28 d; 0, 200 and 2000 MUg Cd L(-1)) toxic effects of
      waterborne Cd were measured in haemocytes and gill cells using differential
      haemocyte cell count, the micronucleus test and the comet assay. During
      subchronic exposure to Cd the relative counts of eosinophils and hyalinocytes
      increased significantly in Cd-exposed mussels while the proportion of basophils
      decreased. All of these effects were time- and concentration-dependent.
      Conversely, the relative numbers of basophils and eosinophils increased
      significantly during acute Cd exposure. Nuclear aberrations such as the formation
      of micronuclei, nuclear buds, fragmented-apoptotic cells and binuclei were
      observed in gill cells of Cd-exposed mussels. All of these parameters increased
      significantly at 2000 MUg Cd L(-1) during subchronic exposure to Cd, and all
      showed a strong and significant correlation to gill Cd accumulation. Comet assay
      results demonstrated a significant increase in DNA damage in the haemocytes of
      mussels exposed to subchronic Cd concentrations. The results indicate that Cd has
      the capacity to induce immune system and genotoxic damage in green-lipped
      mussels, an impact that may have implications such as reduced disease resistance
      and compromised survival. These data also suggest that immunocytotoxic and
      cytogenotoxic biomarkers would be a valuable addition to environmental monitoring
      programmes using green-lipped mussels.

PMID- 24077183
TI  - Modulation of A2B adenosine receptor by 1-Benzyl-3-ketoindole derivatives.
AB  - We have disclosed a series of 1-benzyl-3-ketoindole derivatives acting as either
      positive or negative modulators of the human A(2B) adenosine receptor (A(2B) AR)
      depending on small differences in their side chain. The new compounds were
      designed taking into account structural similarities between AR antagonists and
      ligands of the GABA(A)/benzodiazepine receptor. All compounds resulted totally
      inactive at A(2A) and A3 ARs and showed small (8a,b) or none (7a,b, 8c and 9a,b)
      affinity for A1 AR. When tested on A(2B) AR-transfected CHO cells, 7a,b and 8a
      acted as positive modulators, whereas 8b,c and 9a,b acted as negative modulators,
      enhancing or weakening the NECA-induced increase of cAMP levels, respectively.
      Compounds 7-9 might be regarded as useful biological and pharmacological tools to
      explore the therapeutic potential of A(2B) AR modulators, while their 3
      ketoindole scaffold might be taken as a reference to design new analogs.

PMID- 24077185
TI  - Vitamin A and E profiles as biomarkers of PCB exposure in beluga whales
      (Delphinapterus leucas) from the western Canadian Arctic.
AB  - We evaluated the utility of vitamin A and E profiles as biomarkers of contaminant
      exposure in beluga whales (Delphinapterus leucas; n=66) harvested by the
      Inuvialuit in the Beaufort Sea. Blubber was an important repository for these
      vitamins, accounting for 76.8+/-2.6% of the total body store of vitamin A, and
      98.5+/-0.4% of total vitamin E. While the free alcohol form of vitamin A
      (retinol) appeared highly regulated, the vitamin A esters were influenced by
      several biological factors including age, body condition and length. Vitamin E
      concentrations in liver and blubber were related to age, condition, length and
      feeding ecology, as described delta(15)N and delta(13)C. Despite the influence of
      these factors, collective results from univariate statistics, best fit multiple
      regressions, and principal component analysis (PCA) identified polychlorinated
      biphenyls (PCBs) as important determinants of vitamin concentrations and profiles
      in beluga tissues. Blubber PCB concentrations best explained variation of the
      first principal component in a PCA of hepatic vitamins (r(2)=0.13, p=0.014), and
      regression models found that vitamin A concentrations were negatively correlated
      with PCB levels in liver (esters: r(2)=0.19, p=0.001), but positively in plasma
      (retinol: r(2)=0.20, p=0.06) and blubber (retinol: r(2)=0.22, p=0.001, esters:
      r(2)=0.43, p<0.001). Our analyses provide a basis to propose an integrated
      toxicity reference value for disruption of vitamin A and E profiles in beluga of
      1.6 mg/kg lw PCBs. This disruption of vitamin profiles by moderate levels of PCBs
      in an arctic cetacean highlights the global reach and impact of these legacy
      chemicals decades after their peak use.

PMID- 24077186
TI  - Field study of cyclic hypoxic effects on gene expression in grass shrimp
      hepatopancreas.
AB  - Grass shrimp, Palaemonetes pugio, are widely used for ecological and
      toxicological research. They commonly experience cyclic hypoxia in their natural
      habitats. The response of grass shrimp to laboratory-controlled cyclic hypoxia
      has been studied in detail, but little is known about how field acclimatized
      grass shrimp regulate the gene expression and response to cyclic hypoxia. In this
      study we examined morphometric parameters, relative fecundity and gene expression
      of grass shrimp collected from two areas in Weeks Bay (Mobile, Alabama). One is a
      traditionally normoxic location (WBM), and the other is a traditionally cyclic
      hypoxic location (WC). In the week preceding grass shrimp collection dissolved
      oxygen (DO) at the field sites was measured continuously. DO was <2 (mg/L DO) and
      between 2 and 3 (mg/L DO) for 0 and 255min at WBM, and for 285 and 1035min at WC,
      respectively. Weight and length of WBM grass shrimp were significantly greater
      than weight and length of WC shrimp. WBM shrimp had more eggs than WC shrimp, but
      the difference was not significant. Shrimp from WC had a significant higher
      number of parasites than those from WBM. A cDNA microarray was utilized to
      investigate the changes in gene expression in grass shrimp hepatopancreas. Five
      genes, previously identified as hypoxia/cyclic hypoxia-responsive genes in
      laboratory exposure studies, were significantly up-regulated in WC shrimp
      relative to WBM. A total of 5 genes were significantly down-regulated in the
      field study. Only one of those genes, vitellogenin, has been previously found in
      chronic and cyclic hypoxic studies. Up and down-regulation of 7 selected genes
      was confirmed by qPCR. The overall pattern of gene expression in wild shrimp from
      cyclic DO sites in Weeks Bay showed only weak correlations with gene expression
      in shrimp from chronic and cyclic hypoxic laboratory studies. It appears
      therefore that transcriptome profiles of laboratory acclimated animals are of
      limited utility for understanding responses in field acclimatized animals that
      are exposed to a broader array of environmental variables. 

PMID- 24077187
TI  - Functional and pathway enrichment analysis for integrated regulatory network of
      high- and low-metastatic lung cancer.
AB  - Metastasis is a common feature of lung cancer, involving relationships between
      genes, proteins and miRNAs. However, lack of early detection and limited options
      for targeted therapies are weaknesses that cantribute to the dismal statistics
      observed in lung cancer metastasis. In this paper, gene expression profiling
      analysis for genes differentially expressed between high- (95D) and low
      metastatic lung cancer cell lines (95C) was performed using gene annotation,
      pathway analysis, literature mining, and the integrated regulatory network as
      well as motif analysis of miRNA-DEG and TF-DEG. In addition, the expression of
      EGR-1 (early growth reponse-1) in surgically resected lung squamous carcinomas,
      adenocarcinomas and normal lung tissue was detected by immunohistochemistry to
      reveal the relationships between EGR-1 and lung cancer metastasis. A total of 570
      different expressed genes (DEGs) were screened, the vast majority of up-regulated
      DEGs were connected to cell adhesion and focal adhesion. EGR-1 was observed in
      the center node of the regulatory network, which seems to play a role in the
      process of cancer metastasis, and further immunohistochemistry detection
      confirmed this reasoning. Besides EGR-1, several significant module-related DEGs
      were enriched in the pathway within cancer and focal adhesion according to KEGG
      pathway enrichment analysis of network modules. The construction of an integrated
      regulatory network and the functional prediction of EGR-1 provided us with the
      cytological basis of lung cancer metastasis research and an understanding of the
      mechanism of metastasis in lung cancer. EGR-1 should be considered as a potential
      target gene in therapeutic agent for lung cancer metastasis. 

PMID- 24077188
TI  - Physician response to medtronic's position on the use of off-label medications in
      the synchromed pump.

PMID- 24077189
TI  - Recommendations of the Medicare Payment Advisory Commission (MEDPAC) on the
      Health Care Delivery System: the impact on interventional pain management in 2014
      and beyond.
AB  - Continuing rise in health care costs in the United States, the Affordable Care
      Act (ACA), and a multitude of other regulations impact providers in 2013. Despite
      federal spending slowing in the past 2 years, the Board of Medicare Trustees
      believes that cost savings are only achievable if health care providers are able
      to realize productivity improvements at a quicker pace than experienced
      historically. Consequently, the re-engineering of U.S. health care and bridging
      of the divide between health and health care have been proposed beyond affordable
      care. Thus, the Medicare Payment Advisory Commission (MedPAC) envisions alignment
      of Medicare payment systems to eliminate variable rates for the same ambulatory
      services provided to similar patients in different settings, such as the
      physician's office, hospital outpatient departments (HOPDs), and ambulatory
      surgery centers (ASCs). MedPAC believes that if the same service can be safely
      provided in different settings, a prudent purchaser should not pay more for that
      service in one setting than in another. MedPAC is also concerned that payment
      variations across settings encourage arrangements among providers that result in
      care being provided in high paid settings. MedPAC recommends that payment rates
      be based on the resources needed to treat patients in the most efficient setting,
      adjusting for differences in patient severity, to the extent the severity
      differences affect costs. MedPAC has analyzed the costs of evaluation and
      management (E&M) services and the differences between providing them in a HOPD
      setting compared to a physician office setting, echocardiography services, and
      multiple services provided in ASCs and HOPDs. MedPAC has shown that for an
      established patient office visit (CPT 99213) provided in a free-standing
      physician's office, the program pays the physician 70% less than in HOPD setting
      with a payment for physician practice of $72.50 versus $123.38 for HOPD setting.
      Similarly, for a Level II echocardiogram, HOPD costs 141% more for the same
      service than a free-standing office ($188.31 versus $452.89). For interventional
      techniques, Medicare payments vary from physician office to HOPD setting, with
      $211.96 in an office setting, $407.28 in ASC setting, and $655.62 in HOPD for
      procedures such as epidural injections. The MedPAC proposal for changing HOPD
      payment rates for services would reduce program spending and result in
      beneficiary cost sharing by $900 million in one year. On average, hospitals'
      overall Medicare revenue will decline by 0.6% and HOPD revenue would fall by
      2.7%. Further, MedPAC provided a specific example that aligning payment rates
      between HOPDs and free-standing offices only for cardiac imaging services would
      reduce program spending and beneficiary cost sharing by $500 million in one year.
      In estimating the savings that would be realized by equalizing payment rates
      between HOPDs and ASCs for certain ambulatory surgical procedures, MedPAC have
      shown potential Medicare program spending and beneficiary cost savings to be
      about $590 million per year. The impact of the proposed policies that are
      discussed in this manuscript would result in savings of approximately $1.5
      billion per year for Medicare. MedPAC also has recommended a stop-loss policy
      that would limit the loss of Medicare revenue for those hospitals. 

PMID- 24077190
TI  - Vertebral augmentation versus conservative therapy for emergently admitted
      vertebral compression deformities: an economic analysis.
AB  - BACKGROUND: Vertebral augmentation (VA) performed on inpatients with painful
      osteoporotic vertebral compression fractures (VCFs) has been shown to facilitate
      discharge, decrease analgesic requirements, and improve pain. OBJECTIVE: The
      purpose of our study was to compare the overall cost, length of stay, and
      readmission data for patients hospitalized with painful osteoporotic VCFs,
      treated either medically or with inpatient VA. SETTING: A single academic medical
      center. STUDY DESIGN: Economic analysis METHODS: Patients admitted with VCF over
      a 30-month period were identified using ICD-9 codes. The total length of stay,
      hospitalization costs, average daily cost, and 30-day readmission rates were
      compared between those who underwent VA and those managed nonoperatively. A
      subgroup analysis was performed with an age matched group of controls as well.
      Two-tailed t-tests were used for statistical significance. RESULTS: Thirty-nine
      inpatients underwent VA; 61 levels were augmented. Their average age was 81.7
      years. There were 209 patients who were treated nonoperatively for VCF. Their
      average age was 72.7 years, a significant age difference from the VA group (P <
      0.01). The VA patients' average length of stay was 13.8 days, compared to 8.1
      days in the medically managed group (P < 0.01). Average total costs were $26,074
      in the VA group and $15,507 in the medically managed group (P < 0.01). The daily
      costs of admission were $2,040 in the VA group and $2,069 in the medically
      managed group (P = 0.85). The readmission rates related to VCF were 0% in the VA
      group; 5.2% in the medically managed group; and 7.7% in the age-matched control
      group. Of those who underwent VA, 43% experienced delays in care related to
      anticoagulation or medical comorbidities. LIMITATIONS: The study is retrospective
      and uses billing data as a marker for total cost of care, The study does not
      account for cost differences between vertebroplasty and kyphoplasty. CONCLUSION:
      Inpatient VA can be cost effective as demonstrated by the same daily cost between
      the VA and medically managed groups. Early identification and consultation can
      facilitate VA and rapid discharge. Anticoagulation issues and medical
      comorbidities can delay VA and lengthen hospital stays. Hospital admitted
      patients with painful osteoporotic VCF who are managed conservatively and
      discharged are at risk for readmission.

PMID- 24077191
TI  - Unilateral versus bilateral balloon kyphoplasty for osteoporotic vertebral
      compression fractures.
AB  - BACKGROUND: Osteoporotic vertebral compression fractures (VCFs) commonly occur in
      aged people. Balloon kyphoplasty (KP) has been proven to be efficacious for pain
      relief and reduction of vertebral height for patients with osteoporotic VCFs.
      However, very little is known about the comparison of clinical and radiographic
      outcomes between unilateral and bilateral balloon KP in treating this kind of
      patients. OBJECTIVE: To compare the safety and long-term radiographic and
      clinical outcomes of unilateral or bilateral balloon KP to treat patients with
      osteoporotic VCFs. STUDY DESIGN: A systemic review and meta-analysis of all
      randomized controlled trials (RCTs) comparing the analgesic efficacy,
      radiographic outcomes, and complications between unilateral and bilateral balloon
      KP in patients with osteoporotic VCFs. SETTING: The MEDLINE, EMBASE, Pubmed,
      CINAHL databases, Bandolier, and the Cochrane Controlled Trials Register were
      systematically searched for evidence from their inception to July 2012 by 2 of
      the authors (J.L. and L.Z.). METHODS: Relevant reports were reviewed by 2
      assessors independently and the reference lists of retrieved papers were
      scrutinized to identify further studies for inclusion, using guidelines set by
      PRISMA statement criteria. RESULTS: Three RCTs were enrolled in this study. The
      VAS scores showed no statistical difference between the groups before surgery and
      either at short-term or long-term follow-up. There was no statistical
      significance in polymethylmethacrylate (PMMA) leakage between the groups.
      Analysis of 2 studies showed statistical significance in surgery time (WMD -23.77
      [-27.83, -19.71]; P < 0.00001) and PMMA (WMD -1.65 [-2.28, -1.02]; P < 0.00001)
      consumption between the groups. LIMITATIONS: There were few data sources from
      which to extract abstracted data or published studies. There were only 3 RCTs
      that met criteria enrollment in this meta-analysis. The quality of these trials
      was quite low (Jadad score: 1-2). Variable reporting of end points and
      inconsistent definitions meant that we were not able to include every study for
      each outcome. There was also clinical heterogeneity among the studies.
      CONCLUSION: The efficacy of both unilateral and bilateral balloon KP to provide
      rapid, significant, and sustained pain relief for patients with osteoporotic VCFs
      is validated. Unilateral balloon KP is a reasonable treatment for patients with
      osteoporotic VCFs considering that it could achieve equivalent pain relief with
      less surgery time and PMMA consumption compared to bilateral balloon KP. There
      was no evidence to prove that unilateral balloon KP results in higher incidence
      of PMMA leakage than bilateral balloon KP. Although unilateral balloon KP was
      less efficacious in the reduction of fractured vertebral body, it is still
      unclear if the clinical results of balloon KP were positively correlated with the
      restoration of vertebral height and amount.

PMID- 24077193
TI  - A randomized, double-blind, active control trial of fluoroscopic cervical
      interlaminar epidural injections in chronic pain of cervical disc herniation:
      results of a 2-year follow-up.
AB  - BACKGROUND: A recent evaluation of the state of U.S. health from 1990 to 2010
      placed neck pain as the fourth condition leading to disability, with low back
      pain being the number one. Multiple treatment modalities have been described in
      managing neck and upper extremity pain secondary to cervical disc herniation
      after the failure of conservative management. The treatment modalities for
      chronic persistent pain of cervical disc herniation include surgery and epidural
      injections. The growth of interventional techniques in managing chronic spinal
      pain in recent years has been enormous. Evidence for the efficacy of cervical
      interlaminar epidural injections, however, continues to be debated, despite
      positive evidence derived from controlled randomized trials and systematic
      reviews. STUDY DESIGN: A randomized, double-blind, active control trial. SETTING:
      A private, specialty referral, interventional pain management practice in the
      United States. OBJECTIVES: To evaluate the effectiveness of epidural injections
      in managing chronic pain related to cervical disc herniation. METHODS: Patients
      were randomly assigned to one of 2 groups of 60, with a total of 120 patients.
      Group I patients received cervical epidural injections with lidocaine 0.5%
      preservative-free, 5 mL, whereas Group II patients received 0.5% preservative
      free lidocaine mixed with 1 mL or 6 mg of non-particulate betamethasone. OUTCOME
      ASSESSMENT: Multiple outcome measures included the numeric rating pain scale
      (NRS), the Neck Disability Index (NDI), employment status, opioid intake with
      assessment at 3, 6, 12, 18, and 24 months post treatment. Significant improvement
      was described as pain relief with a 50% improvement in functional status.
      RESULTS: This evaluation showed significant improvement as 50% pain relief and
      improvement in functional status in 72% of the patients at 2 year follow-up in
      the local anesthetic group and 68% in those patients receiving local anesthetic
      and steroid. In the successful group of participants however, significant
      improvement was seen in 77% in Group I and 80% in Group II. Overall, the average
      number of procedures was 5 to 6 in both groups. The average total relief for 2
      years was 75.9 +/- 29.9 weeks in Group I and 72.7 +/- 31.1 in Group II, the
      successful group of participants. Taking into consideration all of the
      participants, the average total relief for 2 years was 69.6 +/- 35 weeks in Group
      I and 62.1 +/- 38.4 weeks in Group II. LIMITATIONS: The results of the study are
      limited by the lack of a placebo group. CONCLUSION: Cervical epidural injections
      with local anesthetic with or without steroids. [corrected].

PMID- 24077192
TI  - Comparing pain reduction following vertebroplasty and conservative treatment for
      osteoporotic vertebral compression fractures: a meta-analysis of randomized
      controlled trials.
AB  - BACKGROUND: Osteoporotic vertebral compression fractures (OVCFs) are the most
      common osteoporotic fractures. Pain is the main symptom. Percutaneous
      vertebroplasty (PVP) is a therapeutic procedure performed to reduce pain in
      vertebral compression fractures. Numerous case series and several small, non
      blinded, non-randomized controlled studies have suggested that vertebroplasty is
      an effective means of relieving pain from osteoporotic fractures. However, a
      recent pooled analysis from 2 multicenter randomized controlled trials concluded
      that the improvement in pain afforded by PVP was similar to placebo. OBJECTIVE:
      To compare the amount of pain reduction measured using the visual analog scale
      when OVCF is treated with vertebroplasty or conservatively, and assess the
      clinical utility of PVP. DESIGN: A meta-analysis and systematic review of
      randomized controlled trials was performed comparing pain reduction following
      vertebroplasty and conservative treatment. LIMITATIONS: There were few data
      sources from which to extract abstracted data or published studies. There were
      only 5 randomized controlled trials that met our criteria. The conservative
      treatments used as comparators in these trials were different. METHODS: A search
      of MEDLINE from January 1980 to July 2012 using PubMed, the Cochrane Database of
      Systematic Reviews and Controlled Trials, CINAHL, and EMBASE. Relevant reports
      were examined by 2 independent reviewers and the references from these reports
      were searched for additional trials, using the criteria established in the QUOROM
      statement. RESULTS: Pooled results from 5 randomized controlled trials are shown.
      There was no difference in pain relief in the PVP group at 2 weeks and one month
      when compared with the conservatively managed group. Pain relief in the PVP group
      was greater than that of the conservative group at 3 months, 6 months, and 12
      months. However, after subgroup analysis, pain scores were similar between the
      PVP group and the sham injection group from 2 weeks to 6 months. Compared with
      non-operative therapy, PVP reduced pain at all times studied. CONCLUSION: PVP has
      some value for relieving pain; however, the possibility of a placebo effect
      should be considered. PVP has gained acceptance as a complementary treatment when
      conservative management has failed before its benefits have been fully
      understood. More large scale, double blinded, controlled trials are necessary in
      order to quantify the pain relief afforded by PVP more precisely.

PMID- 24077194
TI  - Indications for repeat diagnostic medial branch nerve blocks following a failed
      first medial branch nerve block.
AB  - No studies have directly measured the false negative rate of medial branch block
      (MBB) with correlation to medial branch neurotomy (MBN) outcome. We investigated
      the potential false negative MBB rate and the subsequent MBN outcome on a
      consecutive audit of all patients undergoing a double MBB protocol. We
      prospectively collected audit data and retrospectively collected data by phone on
      229 consecutive patients undergoing diagnostic MBB. One-hundred-twenty-two
      patients reporting greater than 50% of subjective pain relief subsequently
      underwent either MBN or a confirmatory block followed by MBN. A total of 55
      patients underwent a second confirmatory MBB and within that group 27.3% (15/55)
      reported less than 50% relief post initial MBB and 30.9% (17/55) between 50% and
      69% relief. We performed an in-depth analysis of these 2 subgroups focusing on
      the reason a second MBB was performed despite a "negative" or "indeterminant"
      first MBB. We divided the "negative" responders to the first MBB into those
      reporting < 50% relief (Group 1) and those reporting between 50% and 69% relief
      (Group 2). We calculated a potential 46.7% false negative rate in Group 1 and
      47.1% false negative in Group 2; however, the false negative results in Group 1
      were predominately in those patients reporting delayed relief of pain and those
      re-blocked greater than 2 years after the first MBB. The success rate in all
      patients undergoing MBN was 87% compared to the 75% relief in the false negative
      groups with no statistically significant difference. In summary, the false
      negative rate for patients reporting less than 50% relief post MBB is probably
      less than 20% although there is a high "apparent negative" responds in patients
      reporting delayed relief or in those who had a second block 2 or more years post
      initial MBB. Patients reporting between 50 and 69% pain relief have a false
      negative response rate of 47.1% and should be considered for a confirmatory
      block. 

PMID- 24077195
TI  - Evaluation of interaction between a spinal cord stimulator and implanted
      cardioverter-defibrillator in a swine model.
AB  - BACKGROUND: Spinal cord stimulators (SCS) have been used for many years to treat
      a myriad of chronic pain conditions using electrical signals to diminish the
      perception of a painful stimulus. Because of the electrical nature of the
      devices, there is a concern about the potential for electromagnetic interaction
      between the device and lifesaving cardiac implantable cardioverters
      defibrillators (ICVD). OBJECTIVE: The purpose of this study was to use a swine
      model to evaluate the potential for interaction between an implanted SCS and ICVD
      using the closest possible proximity, highest stimulation settings, and most
      sensitive ICVD settings. METHODS: A pig was anesthetized and subsequently an ICVD
      and ICVD lead (Cogni 100-D and Endotak Reliance(r), Boston Scientific, Natick,
      MA) were placed into the right prepectoral region and the right ventricle,
      respectively. An SCS (50 cm linear ST Precision Plu octad electrode lead [Boston
      Scientific, Valencia, CA] with 3 mm wide contacts spaced one mm apart- ) was
      implanted using fluoroscopic guidance into the posterior epidural space. Remote
      interrogation and programming of the ICVD were performed while the SCS lead was
      placed in as close proximity as possible, using fluoroscopy to guide the final
      position of the SCS electrode. After confirming that both systems were working,
      appropriately 9 stimulating configurations of varying current, pulse width, and
      frequency, including maximal settings, were delivered through the SCS. The
      effects on the ICVD were recorded at 2 sensitivity settings. RESULTS: None of the
      tested SCS configurations caused interference with the proper functioning of the
      ICVD. LIMITATIONS: The anatomical proximity of the posterior epidural space and
      right ventricle of the swine is different from humans. While the entire pacer,
      including generator, was imbedded in a subcutaneous pocket, an implantable pulse
      generator for the SCS was not implanted, which did not allow us to study if any
      damage or a resetting of settings had occurred to the generator. Only one
      manufacturer was used in this study. Also, this study was performed in an
      anesthetized pig and the anatomical positions remained static. Realistically,
      changes in position of the devices would occur in patients who perform activities
      of daily living, and this can potentially shorten the distance between the 2
      leads causing adverse interaction. CONCLUSION: This study clearly demonstrated
      the feasibility of the 2 devices coexisting and functioning appropriately in an
      animal model using an ICVD and SCS donated by Boston Scientific. Further studies
      are needed to elucidate restrictions, optimal settings and parameters in a human
      setting.

PMID- 24077196
TI  - Concordant pressure paresthesia during interlaminar lumbar epidural steroid
      injections correlates with pain relief in patients with unilateral radicular
      pain.
AB  - BACKGROUND: Transforaminal and interlaminar epidural steroid injections are
      commonly used interventional pain management procedures in the treatment of
      radicular low back pain. Even though several studies have shown that
      transforaminal injections provide enhanced short-term outcomes in patients with
      radicular and low back pain, they have also been associated with a higher
      incidence of unintentional intravascular injection and often dire consequences
      than have interlaminar injections. OBJECTIVES: We compared 2 different
      approaches, midline and lateral parasagittal, of lumbar interlaminar epidural
      steroid injection (LESI) in patients with unilateral lumbosacral radiculopathic
      pain. We also tested the role of concordant pressure paresthesia occurring during
      LESI as a prognostic factor in determining the efficacy of LESI. STUDY DESIGN:
      Prospective, randomized, blinded study. SETTING: Pain management center, part of
      a teaching-community hospital in a major metropolitan US city. METHODS: After
      Institutional Review Board approval, 106 patients undergoing LESI for radicular
      low back pain were randomly assigned to one of 2 groups (53 patients each) based
      on approach: midline interlaminar (MIL) and lateral parasagittal interlaminar
      (PIL). Patients were asked to grade any pressure paresthesia as occurring
      ipsilaterally or contralaterally to their "usual and customary pain," or in a
      distribution atypical of their daily pain. Other variables such as: the Oswestry
      Disability Index questionnaire, pain scores at rest and during movement, use of
      pain medications, etc. were recorded 20 minutes before the procedure, and on days
      1, 7, 14, 21, 28, 60, 120, 180 and 365 after the injection. RESULTS: Results of
      this study showed statistically and clinically significant pain relief in
      patients undergoing LESI by both the MIL and PIL approaches. Patients receiving
      LESI using the lateral parasagittal approach had statistically and clinically
      longer pain relief then patients receiving LESI via a midline approach. They also
      had slightly better quality of life scores and improvement in everyday
      functionality; they also used less pain medications than patients receiving LESI
      using a midline approach. Furthermore, patients in the PIL group described
      significantly higher rates of concordant moderate-to-severe pressure paresthesia
      in the distributions of their "usual and customary pain" compared to the MIL
      group. In addition, patients who had concordant pressure paresthesia and no
      discordant pressure paresthesia (i.e., "opposite side or atypical") during
      interventional treatment had better and longer pain relief after LESI. Two
      patients from each group required discectomy surgery in the one-year observation
      period. LIMITATIONS: The major limitation of this study is that we did not
      include a transforaminal epidural steroid injection group, since that is one of
      the approaches still commonly used in contemporary pain practices for the
      treatment of low back pain with unilateral radicular pain. CONCLUSIONS: This
      study showed that the lateral parasagittal interlaminar approach was more
      effective than the midline interlaminar approach in targeting low back pain with
      unilateral radicular pain secondary to degenerative lumbar disc disease. It also
      showed that pressure paresthesia occurring ipsilaterally during an LESI
      correlates with pain relief and may therefore be used as a prognostic factor.

PMID- 24077197
TI  - Clinical and radiological characteristics of concomitant peripheral arterial
      obstructive disease in patients with lumbar spinal stenosis.
AB  - BACKGROUND: Intermittent claudication is a typical symptom of lumbar spinal
      stenosis (LSS) and peripheral arterial obstructive disease (PAD). Because both
      LSS and PAD are predominantly associated with degenerative conditions,
      concomitant conditions are not uncommon. However, few reports of the demographic,
      clinical, and radiological characteristics of concomitant LSS and PAD (LSSPAD)
      have been published. OBJECTIVE: To identify the demographic, clinical, and
      radiological risk factors for concomitant PAD in LSS. STUDY DESIGN: A
      retrospective matched-control study. METHODS: This study involved a retrospective
      cohort of 43 consecutive patients with LSSPAD and a control cohort of 45 age- and
      gender-matched patients diagnosed with LSS without PAD. Each patient in both
      groups underwent plain lumbar radiographs, magnetic resonance imaging of the
      lumbar spine, and ankle-brachial index (ABI) measurement. Demographic and
      clinical parameters were obtained. The abdominal aorta calcification score (AACS)
      was evaluated on the lateral lumbar radiographs. Computed tomographic angiography
      (CTA) of the lower limb was performed to confirm PAD. RESULTS: The mean age of
      the LSSPAD group was 67.7 +/- 10.7 years (52 - 88 years). The prevalence of
      diabetes mellitus (DM) was significantly higher in the LSSPAD group than in the
      LSS group (P = 0.022). The mean ABI was 0.71 +/- 0.22 (0.32 - 0.91) for the
      LSSPAD group and 0.96 +/- 0.18 (0.83 - 1.10) for LSS group (P < 0.001). The
      prevalence of aortic calcification was significantly higher in the LSSPAD group
      than in the LSS group (P < 0.001). The mean AACS was 10.2 +/- 3.2 (2 - 18) for
      the LSSPAD group and 3.4 +/- 4.1 (0 - 14) for the LSS group (P < 0.001).
      LIMITATIONS: Retrospective design. CONCLUSION: We found that concomitant PAD in
      patients with LSS is associated with old age, DM, the presence of aortic
      calcification, and ABI < 0.9. When these risk factors exist, further work up is
      needed to exclude the concomitant PAD.

PMID- 24077198
TI  - Vertebroplasty augmentation procedures: examining the controversy.
AB  - BACKGROUND: Vertebral compression fractures are a common pathology affecting
      primarily the elderly, postmenopausal women, and those with metastatic vertebral
      disease. Vertebral augmentation procedures are popular treatment options for
      stability and pain relief. Preliminary studies have suggested that such
      procedures are adequately efficacious. However, the first randomized controlled
      trials (RCTs) published in the New England Journal of Medicine in 2009 showed
      that these procedures were not significantly different than placebo with regards
      to pain relief and quality of life. These studies were met with considerable
      criticism. The matter was further complicated when The Lancet published an RCT of
      its own that demonstrated the superiority of vertebroplasty over conservative
      management. The conflicting evidence has sparked ongoing debate in the medical
      community. All sides have provided arguments supported by evidence of varying
      strength and validity. OBJECTIVE: To provide a concise and comprehensive
      presentation of the controversy surrounding vertebral augmentation procedures and
      the evidence cited by proponents on both sides of the debate. METHODS: We began
      by researching the major randomized controlled trials both for and against
      vertebroplasty. These articles were already known to us, and were used as a
      starting point. We then performed a literature search in PubMed for articles
      dated from 2000 through 2012. The bibliographies of major articles and reviews
      were also cross-referenced for additional sources. RESULTS: A number of articles
      that included comprehensive and systematic reviews, meta-analyses, and
      commentaries about noted studies were found. These provided a broad, detailed
      overview of the subject. Many of the common themes of these articles included
      limitations in the design, methods, and patient selection with regard to the RCTs
      and other available studies. LIMITATIONS: This review does not analyze the
      quality of evidence available nor does it provide an opinion in this regard. The
      conclusions of the present article are, therefore, general and descriptive in
      nature. CONCLUSIONS: The arguments presented by proponents of both sides of the
      debate appear to have validity. All of the major studies cited as evidence for or
      against vertebral augmentation procedures have limitations in their quality.
      Consequently, the debate cannot be concluded, convincingly, until more elaborate
      studies are conducted involving larger numbers of patients with clear procedure
      methods agreed upon by the major authorities in the field.

PMID- 24077199
TI  - A randomized, double-blind, active-controlled trial of fluoroscopic lumbar
      interlaminar epidural injections in chronic axial or discogenic low back pain:
      results of 2-year follow-up.
AB  - BACKGROUND: Chronic low back with or without lower extremity pain is extremely
      common, expensive, and disabling. However, all modalities of treatments are
      directed towards disc herniation which is responsible for a very small proportion
      of the patients. Thus, chronic low back pain without disc herniation is common.
      Multiple modalities of treatments are utilized in managing axial or discogenic
      pain including surgery and epidural injections including surgery, intradiscal
      therapies, and epidural injections. However, there is continued debate on the
      effectiveness, indications, and medical necessity of all modalities treatments in
      managing axial or discogenic pain in the lumbar spine. STUDY DESIGN: A
      randomized, double-blind, active control trial. SETTING: A private practice,
      specialty referral, interventional pain management practice in the United States.
      OBJECTIVES: To evaluate the ability to assess the effectiveness of lumbar
      interlaminar epidural injections in managing chronic axial or discogenic low back
      pain with epidural injections of local anesthetic with or without steroids.
      METHODS: In this study, a total of 120 patients were randomly allocated to one of
      the 2 groups receiving either local anesthetic alone or local anesthetic with
      steroids with 60 patients in each group. The primary outcome measure was at least
      50% improvement in the numeric rating scale (NRS) and Oswestry Disability Index
      (ODI). Outcomes were assessed at 3, 6, 12, 18, and 24 months post treatment.
      RESULTS: Significant pain relief and functional status improvement defined as at
      least 50% or more reduction in scores from baseline were observed in 72% of
      patients receiving local anesthetic alone and 67% of the patients receiving local
      anesthetic with steroids. Opioid intake was reduced from baseline in each group
      for 2 years. LIMITATIONS: The results of the study are limited by the lack of a
      placebo group. CONCLUSION: Lumbar interlaminar epidural injections of local
      anesthetic with or without steroids are effective in patients with chronic axial
      low back pain of discogenic origin without facet joint pain, disc herniation,
      and/or radiculitis. TRIAL REGISTRATION: NCT00681447.

PMID- 24077200
TI  - Comparison of balloon kyphoplasty with the new Kiva(r) VCF system for the
      treatment of vertebral compression fractures.
AB  - BACKGROUND: Vertebral compression fractures are common among the elderly, which
      is conditioned by osteoporosis. They cause back pain and limit the patient's
      activities. The Kiva(r) VCF Treatment System is a new device to treat vertebral
      compression fractures. Compared to other methods, the utilization of the Kiva
      System reduces the risk for complications and delivers improvements in back pain
      reduction and functionality. OBJECTIVES: Evaluation of safety and effectiveness
      of the Kiva System in comparison to balloon kyphoplasty on the basis of matched
      pairs. METHODS: 52 patients (47 - 89 years, 68 fractures) were treated with
      balloon kyphoplasty or with the new Kiva System. Back pain and impairment of
      motility were assessed preoperatively and 6 months postoperatively, with the
      Visual Analog Scale (VAS) and Oswestry Disability Index (ODI). The operation time
      and cement extravasation were recorded. Control radiographs were evaluated for
      new fractures and vertebral heights. RESULTS: Mean VAS values in both groups
      improved from preoperatively 87.6 +/- 12.8 and 83.1 +/- 14.9 to 10.8 +/- 20.8 and
      24.6 +/- 11.0 6 months after the treatment. The improvement after 6 months in the
      Kiva group was significantly better than in the balloon kyphoplasty group (P <
      0.0001). Mean ODI scores in both groups also improved from 68.7% +/- 15.8% in the
      Kiva group and 80.6% +/- 8.6% in the balloon kyphoplasty group preoperatively to
      24.8 +/- 18.6% and 33.2 +/- 6.3% 6 months after treatment. The mean operation
      time for the Kiva group was 12.7 +/- 3.7 minutes per vertebra and cement leakage
      occurred in 6 patients. The mean operation time for the balloon kyphoplasty group
      was 34.1 +/- 7.0 minutes per vertebra and cement leakage occurred in 8 patients.
      Anterior and mid vertebral height in the Kiva group increased from preoperatively
      21.06 +/- 7.44 mm and 18.36 +/- 5.64 mm to postoperatively 22.41 +/- 7.14 mm and
      20.41 +/- 6.00 mm. Anterior and mid vertebral height in the balloon kyphoplasty
      group increased from preoperatively 21.68 +/- 2.06 mm and 21.97 +/- 1.78 mm to
      postoperatively 25.09 +/- 2.54 mm and 25.29 +/- 2.10 mm. Vertebral height
      restoration could be therefore maintained with both procedures for 6 months. In
      the Kiva group 2 cases of nonadjacent fractures and one case of adjacent
      fractures were observed. In the balloon kyphoplasty group 9 cases of adjacent, as
      well as 5 cases of nonadjacent, fractures were observed. In the Kiva group
      significant fewer fractures occurred. LIMITATIONS: The study includes only 26
      patients for each procedure, which were compared on the basis of matched pairs.
      CONCLUSION: The Kiva System appears to be a safe and effective procedure for the
      treatment of vertebral compression fractures. Six months after treatment with the
      Kiva System, better VAS values than the values after the treatment with balloon
      kyphoplasty were recorded. Reduction in functional impairment was as successful
      as it was after balloon kyphoplasty. Vertebral height restoration was observed in
      both groups, which was sustained for 6 months. The risk of cement extravasation
      during the Kiva Treatment is nearly the same as in balloon kyphoplasty; however,
      it requires a shorter operation time and produces less new fractures.

PMID- 24077201
TI  - Comparison between radiofrequency targeted vertebral augmentation and balloon
      kyphoplasty in the treatment of vertebral compression fractures: addressing
      factors that affect cement extravasation and distribution.
AB  - BACKGROUND: Both vertebroplasty and balloon kyphoplasty have been described for
      treatment of vertebral compression fractures. Vertebroplasty is known for its
      high leakage rate compared with balloon kyphoplasty. In vitro studies have shown
      that high-viscosity cements significantly decrease the incidence of cement
      leakage and increase the predictability of cement fill in cancellous bonelike
      substrates compared with low-viscosity cements. OBJECTIVE: This study compares
      the incidence and pattern of cement leakage in cases treated with standard
      balloon kyphoplasty (BKP) and a novel vertebral augmentation procedure,
      radiofrequency targeted vertebral augmentation (RF-TVA). STUDY DESIGN:
      Retrospective evaluation of postoperative radiographs. SETTING: Single center
      inpatient and outpatient population. METHODS: Two methods of vertebral
      augmentation were utilized. Conventional bipedicular BKP and RF-TVA, a novel
      unipedicular technique which uses a navigational osteotome to create targeted,
      bone sparing cavities and RF energy to deliver an ultra-high viscosity cement at
      a consistent rate via a remote controlled, automated hydraulic delivery system.
      Postoperative radiographs of patients treated with the 2 techniques were
      critically analyzed for the incidence and location of cement leakage. Eighty
      consecutive patients with 106 treated levels were included. Thirty-five patients
      with 49 levels in the BKP and 45 patients with 57 levels in RF-TVA group were
      evaluated. RESULTS: Leakages less than 1-2 mm were not reported since they may
      not represent any clinical significance. In the BKP group, 6 leakages (12%) were
      reported (3 discal, 2 venous, one paravaertebral, and no epidural). In the RF-TVA
      group, a total of 3 leakages (5%) were reported, (one discal, 2 venous, no
      paravaertebral or epidural). Using contingency analysis for leakage per level,
      there was a statistical difference for leakage between RF-TVA and standard BKP, P
      < 0.01. LIMITATIONS: Retrospective study, single center. CONCLUSIONS: The RF-TVA
      technique may provide an approximately 50% reduction in leakage rate when
      compared to standard BKP. This may be related to the combination of controlled
      delivery of radiofrequency activated (high viscosity) cement at a fixed, low rate
      of delivery into site-specific channels created using a navigational osteotome.
      Additionally, based on the unipedicular access and remotely controlled cement
      delivery RF-TVA may decrease procedural invasiveness and physician radiation
      exposure, respectively.INSTITUTIONAL REVIEW: This study was approved by the
      Institutional Review Board.

PMID- 24077202
TI  - Criteria for the appropriate treatment of osteoporotic vertebral compression
      fractures.
AB  - BACKGROUND: The heterogeneity of patients with osteoporotic vertebral compression
      fractures (VCF) necessitates a tailored approach of balancing the benefits and
      limitations of available treatments. Current guidelines are divergent, sometimes
      contradictory, and often insufficiently detailed to guide practice decisions.
      OBJECTIVES: This study aimed at establishing treatment recommendations at the
      patient-specific level. STUDY DESIGN: Using the RAND/UCLA Appropriateness Method
      (RAM), the appropriateness of different treatment options for osteoporotic VCFs
      was assessed. SETTING: The assessment was conducted by a European
      multidisciplinary panel of 12 experts. METHODS: The appropriateness of non
      surgical management (NSM), vertebroplasty (VP), and balloon kyphoplasty (BKP) was
      determined for 128 hypothetical patient profiles. These were unique combinations
      of clinical factors considered relevant to treatment choice (time since fracture,
      MRI findings, impact and evolution of symptoms, spinal deformity, ongoing
      fracture process, and pulmonary dysfunction). After 2 individual rating rounds
      and plenary meetings, appropriateness statements (appropriate, inappropriate, and
      uncertain) were calculated for all clinical scenarios. RESULTS: Disagreement
      dropped from 31% in the first round to 7% in the second round. Appropriateness
      outcomes showed specific patterns for the 3 treatments. For three-quarters of the
      profiles, only one treatment was considered appropriate: NSM 25%, VP 6%, and BKP
      45%. NSM was usually appropriate in patients with a negative MRI or a positive
      MRI without other unfavorable conditions (poor outcomes for the other variables).
      VP was usually appropriate in patients with a positive MRI, time since fracture
      >= 6 weeks, and no spinal deformity. BKP was recommended for all patients with an
      ongoing fracture process, and also in most patients with a positive MRI and >= 1
      other unfavorable factor. LIMITATIONS: The prevalence of the patient profiles in
      daily practice is yet unknown. CONCLUSION: The panel results may help to support
      treatment choice in the heterogeneous population of patients with osteoporotic
      VCF.

PMID- 24077203
TI  - Evaluation of prognostic predictors of percutaneous adhesiolysis using a Racz
      catheter for post lumbar surgery syndrome or spinal stenosis.
AB  - BACKGROUND: Percutaneous adhesiolysis (PA) is considered to be a reasonable
      nonoperative treatment for herniation of intervertebral disc (HIVD), spinal
      stenosis, and post-lumbar-surgery syndrome (PLSS). The success of PA depends on
      the removal of epidural fibrosis and drug delivery to the target region. However,
      prognostic predictors of the effects of PA are not well known. OBJECTIVE: The aim
      of this study was to evaluate prognostic predictors of PA using a Racz catheter
      for patients with PLSS or spinal stenosis. STUDY DESIGN: Retrospective
      assessment. METHODS: PA using a Racz catheter was performed on 78 patients. We
      assessed the effectiveness of PA at pretreatment, 2 weeks, 3 months, and 6 months
      following the procedure. Effectiveness was defined as a 50% or more reduction of
      the Numeric Rating Scale (NRS) for back and leg pain or a 40% or more reduction
      of the Oswestry Disability Index (ODI) following the procedure. Data collected
      for each patient included age, gender, BMI, grade and location of stenosis in
      magnetic resonance imaging (MRI), symptom durations, and history of previous
      lumbar surgery. The adjusted odds ratios (OR) and 95% confidence intervals (CI)
      for each variable were analyzed by logistic regression. RESULTS: PA using a Racz
      catheter was more effective in patients with no previous lumbar surgery (OR,
      7.426; 95% CI, 1.820-30.302; P = 0.005) or root compression with HIVD or
      foraminal stenosis (OR, 5.479; 95% CI, 1.137-26.391; P = 0.036). Other included
      factors were not related to PA effectiveness. LIMITATIONS: The number of patients
      examined in this study was relatively small. CONCLUSION: Good prognostic
      predictors were identified as no previous lumbar surgery or root compression with
      HIVD or foraminal stenosis. These results are expected to contribute to the
      establishment of indications for PA.

PMID- 24077204
TI  - Ultrasound-guided trigeminal nerve block via the pterygopalatine fossa: an
      effective treatment for trigeminal neuralgia and atypical facial pain.
AB  - BACKGROUND: Patients presenting with facial pain often have ineffective pain
      relief with medical therapy. Cases refractory to medical management are
      frequently treated with surgical or minimally invasive procedures with variable
      success rates. We report on the use of ultrasound-guided trigeminal nerve block
      via the pterygopalatine fossa in patients following refractory medical and
      surgical treatment. OBJECTIVE: To present the immediate and long-term efficacy of
      ultrasound-guided injections of local anesthetic and steroids in the
      pterygopalatine fossa in patients with unilateral facial pain that failed
      pharmacological and surgical interventions. SETTING: Academic pain management
      center. STUDY DESIGN: Prospective case series. METHODS: Fifteen patients were
      treated with ultrasound-guided trigeminal nerve block with local anesthetic and
      steroids placed into the pterygopalatine fossa. RESULTS: All patients achieved
      complete sensory analgesia to pin prick in the distribution of the V2 branch of
      the trigeminal nerve and 80% (12 out of 15) achieved complete sensory analgesia
      in V1, V2, V3 distribution within 15 minutes of the injection. All patients
      reported pain relief within 5 minutes of the injection. The majority of patients
      maintained pain relief throughout the 15 month study period. No patients
      experienced symptoms of local anesthetic toxicity or onset of new neurological
      sequelae. LIMITATIONS: Prospective case series. CONCLUSION: We conclude that the
      use of ultrasound guidance for injectate delivery in the pterygopalatine fossa is
      a simple, free of radiation or magnetization, safe, and effective percutaneous
      procedure that provides sustained pain relief in trigeminal neuralgia or atypical
      facial pain patients who have failed previous medical interventions.

PMID- 24077205
TI  - Combinations of low-dose antidepressants and low-dose pregabalin as useful
      adjuvants to opioids for intractable, painful bone metastases.
AB  - BACKGROUND: Systemic analgesics would not provide good enough pain relief for
      some kinds of cancer pain. Metastatic bone pain is characteristic of one of the
      refractory cancer pains, since the pain is not only nociceptive but also
      neuropathic. A low-dose antiepileptic-antidepressant combination with opioids is
      effective in the management of neuropathic cancer pain. OBJECTIVE: The aim was to
      see whether a low-dose antiepileptic-antidepressant combination is effective in
      the treatment of bone metastases. STUDY DESIGN: Randomized, controlled trial.
      SETTING: Pain Clinic in Japan. METHODS: Thirty-seven cancer patients, confirmed
      to have bone metastases, were allocated into 3 groups: P group took pregabalin 50
      mg every 8 hours orally; P-I group took pregabalin 25 mg every 8 hours orally and
      imipramine 5 mg every 12 hours orally; P-M group took pregabalin 25 mg every 8
      hours orally and mirtazapine 7.5 mg every 12 hours orally. Pain assessments were
      performed for 2 weeks. RESULTS: The total pain score significantly decreased in
      all 3 groups even one day after the start of the medication. The decreases in the
      P-I and P-M groups were significantly greater than those in the P group from Day
      2. Also, the daily paroxysmal pain episodes significantly decreased in all 3
      groups at Day one. The decreases in the P-M groups were significantly greater
      than those in the P group from Day one. The decreases in the P-I group were
      significantly greater than those in the P group from Day 3. CONCLUSION: Low-dose
      pregabalin-antidepressant combinations with opioids were effective in the
      management of painful bone metastases.

PMID- 24077206
TI  - Dual reuptake inhibitor milnacipran and spinal pain pathways in fibromyalgia
      patients: a randomized, double-blind, placebo-controlled trial.
AB  - BACKGROUND: Investigations based on quantitative sensory testing have
      consistently shown evidence of allodynia in fibromyalgia syndrome (FMS) patients
      involving both the spinal and supraspinal pain regulatory systems. Functional
      imaging studies have demonstrated enhanced neural activities in pain-related
      brain areas as well as impairment of pain inhibition in the descending
      nociceptive regulatory system. A higher state of excitability of spinal
      nociceptive neurons as evidenced by lowered nociceptive flexion reflex R-III
      (NFR) threshold was reported for FMS patients. The NFR procedure has been shown
      to be a valuable tool to evaluate pharmacologically active therapeutic agents at
      the spinal level. OBJECTIVE: Serotonin-noradrenaline reuptake inhibitors have
      been shown to reduce pain in FMS patients possibly through descending
      monoaminergic pain pathways modulation. This randomized double-blind placebo
      controlled trial assessed the pharmacodynamic activity of the dual-reuptake
      inhibitor milnacipran (MLN) at the spinal level by means of the objective spinal
      NFR. STUDY DESIGN: Randomized, double-blind, placebo-controlled trial. SETTING: A
      single academic medical center, outpatient setting. METHODS: Seven-week exposure
      (100, 150, 200mg/day) in women fibromyalgia patients. Evaluation consisted of
      extensive quantitative sensory testing including determination of the NFR
      threshold, self-reported standard questionnaires investigating pain, visual
      analog scales, fibromyalgia impact, health-related quality of life, depression
      and anxiety questionnaires, as well as the Patient's Global Impression of Change
      (PGIC). Analysis of covariance adjusted for baseline value was used for all
      endpoints. RESULTS: Seventy-seven (39 placebo, 38 milnacipran all doses) out of
      80 randomized patients were available for analysis. The absence of influence of
      MLN (any dose) on the NFR surprisingly contrasted with the dose-dependent
      analgesic effect observed in MLN-treated patients with an adjusted change
      difference of -18.4mm (-30.9; -5.8) in pain reduction between placebo and the
      maximum dosage (200 mg) MLN groups (P = 0.02). Unchanged depression and anxiety
      scores confirmed the predominant selectivity of the analgesic effect of MLN on
      nociceptive pain pathway. Self-reported questionnaires consistently reflected the
      positive effects of MLN on quality of life and psychological well-being. Odds
      ratio 5.1 for PGIC responders (i.e. much/very much improved) was significantly in
      favor of MLN (P = 0.04). CONCLUSION: Milnacipran has a predominantly supraspinal
      analgesic effect as evidenced by the significant clinical benefits and the
      absence of changes in the nociceptive spinal reflex threshold. Higher dose was
      associated with higher pain reduction. Reported analgesia was independent of
      patients' emotional status.

PMID- 24077207
TI  - Magnesium L-threonate prevents and restores memory deficits associated with
      neuropathic pain by inhibition of TNF-alpha.
AB  - BACKGROUND: Clinical studies have shown that about two-thirds of patients with
      chronic pain suffer from short-term memory (STM) deficits and an effective drug
      for treatment of the neurological disorder is lacking at present. OBJECTIVE: We
      tested whether chronic oral application of magnesium L-threonate (MgT), which has
      been shown to improve memory in normal and aging animals by elevating Mg2+ in the
      brain, could prevent or restore the STM deficits induced by spared nerve injury
      (SNI), an animal model of chronic neuropathic pain. The mechanisms underlying the
      effect of MgT on STM deficits were also investigated. STUDY DESIGN: The
      experiments were conducted in a random and double-blind fashion in adult male
      rats. MgT was administrated via drinking water at a dose of 609 mg/kg/d for 2
      weeks, starting either one week before SNI (preventative group) or one week after
      SNI (therapeutic group), and water without the drug served as control. METHODS:
      STM was accessed with a novel object recognition test (NORT), followed by
      recording of long-term potentiation (LTP) in the hippocampus in vivo and the
      measurement of the expression of tumor necrosis factor-alpha (TNF-alpha) with
      Western Blot or Immunohistochemistrical staining, a-amino-3-hydroxy-5-methyl-4
      isoxazole-propionic acid (AMPA) and N-methyl-D-aspartic acid (NMDA) receptor
      (NMDAR) currents were recorded with patch clamp in CA1 neurons in acute and
      cultured hippocampal slices. RESULT: We found that chronic oral application of
      MgT was able to prevent and restore the deficits of STM and of LTP at CA3-CA1
      synapses in the hippocampus induced by SNI. Furthermore, both preventative and
      therapeutic chronic oral application of MgT blocked the up-regulation of TNF
      alpha in the hippocampus, which has been previously shown to be critical for
      memory deficits. SNI reduced NMDAR current and the effect was dramatically
      attenuated by elevating extracellular Mg2+ concentration ([Mg2+]?). In cultured
      hippocampal slices, chronic application of recombinant rat TNF-alpha (rrTNF
      alpha) for 3 days reduced NMDAR current in a concentration-dependent manner and
      the effect was again blocked by elevating [Mg2+]?. LIMITATIONS: We showed that
      oral application of MgT inhibited the over-expression of TNF-alpha and rescued
      the dysfunction of the NMDAR, but the causal relationship between them remains
      elusive. CONCLUSIONS: Our data suggested that oral application of MgT was able to
      prevent and restore the STM deficits in an animal model of chronic neuropathic
      pain by reversing the dysfunction of the NMDAR, and normalization of TNF-alpha
      expression may play a role in the effect. Oral application of MgT may be a simple
      and potent means for handling this form of memory deficit.

PMID- 24077208
TI  - Chronic constriction injury induced long-term changes in spontaneous membrane
      potential oscillations in anterior cingulate cortical neurons in vivo.
AB  - BACKGROUND: Neuropathic pain induction by nerve injury has been shown by in vitro
      studies to be accompanied by synaptic strengthening in the anterior cingulate
      cortex (ACC) and has been shown by pharmacological studies in vivo to be
      prevented by blocking N-methyl-D-aspartate (NMDA) receptor-dependent ACC
      plasticity. These findings indicate that ACC neurons undergo nerve injury-induced
      synaptic modifications and further raise a new question about neuropathic pain
      associated changes in neuronal activity in the ACC in vivo, particularly
      spontaneous neuronal oscillations - a process believed to be fundamental for many
      forms of brain function. OBJECTIVE: In this study, we examined the change of
      spontaneous membrane-potential (MP) oscillations in the ACC in vivo in a
      neuropathic pain animal model of chronic constriction injury (CCI), which may
      account for neuropathic pain development, as well as pain hypersensitivity and
      spontaneous pain. STUDY DESIGN: Experimental trial in rats. METHODS: Neuropathic
      pain rats were produced by CCI surgery on the common sciatic nerve. Neuropathic
      pain-related behaviors were accessed by evoked responses to both mechanical and
      thermal stimuli, as well as spontaneous pain indicated by spontaneous foot
      lifting. In vivo whole-cell recording was performed in both control and
      neuropathic pain rats under anaesthesia. MP and action-potential (AP) changes of
      layer II/III ACC pyramidal cells were measured in current-clamp mode. The level
      of anaesthesia was evaluated by monitoring respiratory and heart rates in some
      experiments. RESULTS: Within 7 to 14 days after CCI surgery, the frequency of MP
      oscillations of ACC neurons was found to be significantly higher than that in
      control rats. Such an increase in oscillation frequency after surgery was not due
      to periphery transmission via the sciatic nerve subjected to CCI surgery and was
      indicated to be accounted for by neuronal modifications in the central nervous
      system. Furthermore, this increase was found to result in a higher overall level
      of MP excitation as well as an increase in spontaneous AP firing. LIMITATIONS:
      Our findings in MP and AP changes were obtained in anaesthetized brains; this
      issue remains to be further examined by using whole-cell recording in awake
      behaving animals. CONCLUSIONS: Neuropathic pain is accompanied by the increase in
      rates of spontaneous oscillations of ACC neurons. This change may be critical for
      neuropathic pain development, as well as pain hypersensitivity and spontaneous
      pain in neuropathic pain animals.

PMID- 24077209
TI  - Catechol-O-methyltransferase Val158Met polymorphism is associated with pain and
      disability, but not widespread pressure pain sensitivity, in women with carpal
      Tunnel syndrome.
AB  - BACKGROUND: The genetic influence of Val158Met polymorphisms, one of the
      potential genetic determinants for nociceptive processing, has not been
      previously investigated in women with carpal tunnel syndrome (CTS). OBJECTIVES:
      To investigate the association between the Val158Met polymorphism with CTS and to
      assess the relationship between the Val158Met polymorphism and the clinical
      outcomes and widespread pressure pain hypersensitivity in women with CTS. STUDY
      DESIGN: Case control study. SETTING: Neurology department at an urban hospital.
      METHOD: One hundred nine (n = 109) women (mean age: 47 +/- 9 years) with a
      clinical and electrodiagnostic diagnosis of CTS and 109 matched healthy women
      participated. After amplifying the Val158Met polymorphism by polymerase chain
      reactions, rs4680 genotype frequencies and allele distributions were calculated.
      We classified individuals according to their Val158Met polymorphism: Val/Val,
      Val/Met, Met/Met. The intensity of the pain was assessed with a numeric rating
      scale (0-10) and disability was determined with the Boston Carpal Tunnel
      Questionnaire. Pressure pain thresholds were bilaterally assessed over median,
      radial, and ulnar nerve trunks; C5-C6 facet joints; and carpal tunnel and
      tibialis anterior muscles.Institutional Review Board: The study project was
      approved by the local human research committee (HUFA-12/14). All participants
      signed an informed consent prior to their inclusion in the study. RESULTS: The
      distribution of the 3 Val158Met genotypes (Val/Val, Val/Met, Met/Met) and alleles
      was not significantly different between women with CTS and healthy women (Chi
      Square = 0.498; P = 0.780). Women with CTS carrying the Met/Met genotype showed
      higher levels of pain and disability than those with the Val/Met genotype (P <
      0.01) and with the Val/Val genotype (P < 0.001). No differences in the years with
      pain (P = 0.954), age (P = 0.740), depression (P = 0.530), severity of CTS (P =
      0.744) or presence of unilateral-bilateral symptoms (P = 0.279) existed depending
      on the rs4680 Val158Met genotype. No significant differences in widespread
      pressure pain sensitivity were observed in any of the points depending on the
      rs4680 Val158Met genotype (P > 0.315). LIMITATIONS: We only recruited women from
      a specialized department. CONCLUSION: Current results indicated that the
      Val158Met polymorphism seems not to be a risk factor for the development of CTS;
      however, it was associated with increased perception of pain and higher
      disability scores.

PMID- 24077210
TI  - Pulsed radiofrequency modulates pain regulatory gene expression along the
      nociceptive pathway.
AB  - BACKGROUND: Pulsed radiofrequency (PRF) therapy is a clinical treatment utilizing
      electromagnetic energy aimed to relieve neuropathic pain. This is the first study
      examining the modulated expression of pain regulatory genes following the
      induction of the spared nerve injury (SNI) pain model and subsequently treated
      with PRF therapy. OBJECTIVES: The present study investigated the behavioral
      efficacy of PRF therapy in rats exhibiting sciatic nerve injury and examined gene
      expression changes in the sciatic nerve, ipsilateral L5 dorsal root ganglia
      (DRG), and spinal cord. STUDY DESIGN: A randomized, experimental trial. SETTING:
      Department of Biological Sciences, Illinois State University and Department of
      Psychology, Illinois Wesleyan University. METHODS: An SNI model was used in male
      Sprague-Dawley rats (weight 260-310 g). A sham surgery was also performed as a
      control group. After 3 days development of the SNI model, an RF electrode was
      applied to the sciatic nerve proximal to the site of injury and stimulated for 3
      minutes. The response to mechanical stimuli was assessed throughout the duration
      of the study. Furthermore, changes in gene expression along the nociceptive tract
      (sciatic nerve, DRG, and spinal cord) were assessed 24 hours post-PRF therapy.
      RESULTS: It was observed that the mechanical allodynia, induced by SNI model, was
      reversed to control values within 24 hours post-PRF therapy. Additionally,
      modulated expression of pain regulatory genes was observed after induction of the
      SNI model. Following PRF therapy, expression of many of these genes returned to
      control values (sham) in each of the tissues tested. Increased proinflammatory
      gene expression, such as TNF-alpha and IL-6, observed in the sciatic nerve (site
      of injury) in the SNI group was returned to baseline values following PRF
      therapy. Up-regulation of GABAB-R1, Na/K ATPase, and 5-HT3r as well as down
      regulation of TNF-alpha and IL-6 were also observed in the DRG in the SNI-PRF
      group relative to the SNI group. Up-regulation of Na/K ATPase and c-Fos was found
      in the spinal cord following PRF treatment relative to the SNI group.
      LIMITATIONS: Immediate changes in gene expression were observed at 24 hours to
      better determine the mechanism with no long-term data at this time. Protein
      expression was not assessed in addition to gene expression changes. CONCLUSION:
      These results indicate that the electromagnetic energy applied via PRF therapy
      influences the reversal of behavioral and molecular effects of hypersensitivity
      developed from a peripheral nerve injury.

PMID- 24077211
TI  - Intrathecal lentivirus-mediated transfer of interleukin-10 attenuates chronic
      constriction injury-induced neuropathic pain through modulation of spinal high
      mobility group box 1 in rats.
AB  - BACKGROUND: Neuropathic pain is a complex state of chronic pain that is usually
      accompanied by peripheral and central nervous system damage or dysfunction.
      Previous studies have indicated that neuroinflammation in the spinal cord is an
      important contributor to neuropathological and behavioral abnormalities. A series
      of early inflammatory markers, such as IL-1, TNF-alpha, and IFN-gamma, and
      advanced inflammatory markers, such as high-mobility group box 1 (HMGB1), are
      involved in neuroinflammation. STUDY DESIGN: A randomized, double blind,
      controlled animal trial. OBJECTIVE: In this study, a lentivirus delivering human
      IL-10 (LV/hIL-10) was administered intrathecally to determine the effects of IL
      10 on allodynia and hyperalgesia in a chronic constriction injury-induced (CCI)
      rat model of neuropathic pain. METHODS: Sprague-Dawley rats weighting 260 - 320 g
      were randomly divided into 4 groups. Group Sham (Sham), Group CCI+/-Normal Saline
      (NS), Group CCI+/-LV/hIL-10 (LV/hIL-10), and Group CCI+/-LV/control (vector).
      Rats in each group were intrathecally delivered with NS, LV/control, or
      recombinant vector LV/hIL-10 in a total volume of 10 MUl. Paw withdrawal
      mechanical thresholds (PWMT) and paw withdrawal thermal latency PWTL were
      measured one day before CCI (baseline) and 0, 3, 7, 14, and 28 days after
      intrathecal administration. Cerebrospinal fluid (CSF) samples were collected
      during surgical plane anesthesia and the collected CSF samples were used to assay
      for human IL-10, rat IL-1beta, rat IL-6, and rat TNF-alpha by enzyme-linked
      immunosorbent assay (ELISA). Animals were sacrificed and the L4-5 lumbar segment
      of the spinal cord was removed for determination of green fluorescent protein
      (GFP) expression. Immunohistochemical analysis was performed using anti HMGB1
      antibodies and the expression of HMGB1 protein in the spinal cord was determined
      by western blot analysis after intrathecal delivery (n = 8 each). RESULTS: The
      results show that intrathecal LV/hIL-10 reverses enhanced pain states. Moreover,
      the increased level of HMGB1 exhibited in a late stage of CCI was inhibited by
      exogenous overexpression of hIL-10 in the CCI model. Expression of HMGB1, RAGE,
      and pAkt were lower in CCI-induced rats treated with LV/hIL-10 than in those
      treated with LV/control (vector) or saline (NS). Our results showed that IL-10
      inhibits activation of the inflammatory HMGB1-RAGE pathway in the CCI rat model.
      LIMITATIONS: Further experimental investigations are needed to clarify the
      specific biological roles played by HMGB1 in IL-10-mediated regulation of
      neuropathic pain. CONCLUSION: Our results indicate that intrathecal lentiviral
      mediated transfer of IL-10 attenuates CCI-induced neuropathic pain in rats. The
      anti-thermal hyperalgesia and anti-mechanical allodynia may be partly
      attributable to the decreased expression of HMGB1 and inhibition of HMGB1-RAGE
      pathway.

PMID- 24077212
TI  - False positive radiographical evidence of pump catheter migration into the spinal
      cord.
AB  - Intrathecal drug delivery systems are becoming an increasingly common modality
      used by physicians to treat patients. Specifically, chronic spasticity secondary
      to multiple sclerosis (MS) may be treated with intrathecal baclofen (ITB) therapy
      when oral antispasmodics do not provide adequate relief. ITB therapy is
      effective, localizes drug delivery, and does not have the same degree of
      intolerable systemic effects often seen with oral and parenteral medications. As
      the use of intrathecal drug delivery systems has become more common, so has the
      incidence of adverse events. ITB administration requires the surgical
      implantation of indwelling catheters and a pump reservoir. Although this therapy
      is useful in treating spasticity, risks unique to intrathecal drug delivery
      systems include medication dosing errors, pump malfunction, infection, and
      catheter breakage or dislocation. To our knowledge intrathecal pump catheter
      migration into the spinal cord is a very rare complication with only 2 such
      complications reported. We present a case of an intrathecal baclofen pump
      catheter that was initially believed to have migrated into the spinal cord and
      the innovative use of cinefluoroscopy and digital subtraction used to identify
      catheter placement. Moreover, after confirmation of the catheter position within
      the spinal cord on magnetic resonance imaging (MRI) our team elected to perform a
      laminectomy, which demonstrated that the catheter was not in the spinal cord but
      was surrounded by arachnoid adhesions. We hope our efforts will provide the
      clinician insight into the common difficulties that arise and how best to
      troubleshoot them to serve this specific patient population and prevent
      potentially life-threatening complications. 

PMID- 24077213
TI  - Using pulsed radiofrequency ablation to treat pain associated with a tumor
      involving the brachial plexus: a molecular mechanism.

PMID- 24077214
TI  - Serotonin syndrome with perioperative oxycodone and pregabalin.

PMID- 24077215
TI  - Optimum nanoparticles for electrocatalytic oxygen reduction: the size, shape and
      new design.
AB  - The electrocatalytic oxygen reduction reaction (ORR) on nanoparticles has
      attracted much attention in recent years for its significance in fuel cell
      applications. Here by combining density functional theory (DFT) calculations with
      the periodic continuum solvation model based on modified-Poisson-Boltzmann (CM
      MPB) electrostatics, we analyzed the ORR activity on a set of differently sized
      Pt nanoparticles in order to identify the optimum particles for a better designed
      catalyst. We show that Pt nanoparticles of ~2 nm size have the highest ORR mass
      activity, which is attributed to the variation of the effective reaction sites on
      the exposed {111} facet at the electrochemical conditions. We propose a type of a
      new nanocatalyst for the electrocatalytic oxygen reduction based on the knowledge
      from large-scale first principles simulations on Pt nanoparticles. The new
      catalyst has inert metal Au as the frame for the Pt nanoparticle and exposed
      Pt{111} sites are the active site for oxygen reduction. Such an architecture can
      not only prevent the initial O corrosion at the edge sites but also significantly
      improve the activity. The theoretical work provides a promising new direction for
      the rational design of a stable and active ORR catalyst via nano-structure
      engineering. 

PMID- 24077217
TI  - Trace Ratio Linear Discriminant Analysis for Medical Diagnosis: A Case Study of
      Dementia.
AB  - Dementia is one of the most common neurological disorders among the elderly.
      Identifying those who are of high risk suffering dementia is important to the
      administration of early treatment in order to slow down the progression of
      dementia symptoms. However, to achieve accurate classification, significant
      amount of subject feature information are involved. Hence identification of
      demented subjects can be transformed into a pattern recognition problem with high
      dimensional nonlinear datasets. In this paper, we introduce trace ratio linear
      discriminant analysis (TR-LDA) for dementia diagnosis. An improved ITR algorithm
      (iITR) is developed to solve the TR-LDA problem. This novel method can be
      integrated with advanced missing value imputation method and utilized for the
      analysis of the nonlinear datasets in many real-world medical diagnosis problems.
      Finally, extensive simulations are conducted to show the effectiveness of the
      proposed method. The results demonstrate that our method can achieve higher
      accuracies for identifying the demented patients than other state-of-art
      algorithms.

PMID- 24077218
TI  - Experimental research on the effectiveness of speed reduction markings based on
      driving simulation: a case study.
AB  - The objective of this paper is to test the effectiveness of speed reduction
      markings (SRMs). The empirical data including vehicle operations and drivers'
      psychological and physical reactions were collected in a driving simulator. An
      index-the relative speed difference-was developed to evaluate the effectiveness
      of speed reduction markings. Researchers analyzed data to test the effectiveness
      of speed reduction markings and quantitatively study their effects and the
      deceleration process. Out of 15 subjects, there were 1 (7%), 2 (13%), and 7 (47%)
      subjects who decelerated while driving through the downhill section in the No
      SRMs scenario, Longitudinal SRMs scenario and Transverse SRMs scenario,
      respectively. In terms of speed and subjects' decelerating maneuver, the results
      of the analysis of variance (ANOVA) and the contrast analysis (S-N-K method)
      showed that transverse speed reduction markings (TSRMs) could significantly
      influence subjects' speed choice and maneuver (P<0.05). 

PMID- 24077216
TI  - MiRNAs confer phenotypic robustness to gene networks by suppressing biological
      noise.
AB  - miRNAs are small non-coding RNAs able to modulate target gene expression. It has
      been postulated that miRNAs confer robustness to biological processes, but clear
      experimental evidence is still missing. Here, using a synthetic biological
      approach, we demonstrate that microRNAs provide phenotypic robustness to
      transcriptional regulatory networks by buffering fluctuations in protein levels.
      We construct a network motif in mammalian cells exhibiting a 'toggle-switch'
      phenotype in which two alternative protein expression levels define its ON and
      OFF states. The motif consists of an inducible transcription factor that self
      regulates its own transcription and that of a miRNA against the transcription
      factor itself. We confirm, using mathematical modelling and experimental
      approaches, that the microRNA confers robustness to the toggle-switch by enabling
      the cell to maintain and transmit its state. When absent, a dramatic increase in
      protein noise level occurs, causing the cell to randomly switch between the two
      states. 

PMID- 24077219
TI  - Motion-compensated PET image reconstruction with respiratory-matched attenuation
      correction using two low-dose inhale and exhale CT images.
AB  - Positron emission tomography (PET) is widely used for diagnosis and follow up
      assessment of radiotherapy. However, thoracic and abdominal PET suffers from
      false staging and incorrect quantification of the radioactive uptake of lesion(s)
      due to respiratory motion. Furthermore, respiratory motion-induced mismatch
      between a computed tomography (CT) attenuation map and PET data often leads to
      significant artifacts in the reconstructed PET image. To solve these problems, we
      propose a unified framework for respiratory-matched attenuation correction and
      motion compensation of respiratory-gated PET. For the attenuation correction, the
      proposed algorithm manipulates a 4D CT image virtually generated from two low
      dose inhale and exhale CT images, rather than a real 4D CT image which
      significantly increases the radiation burden on a patient. It also utilizes CT
      driven motion fields for motion compensation. To realize the proposed algorithm,
      we propose an improved region-based approach for non-rigid registration between
      body CT images, and we suggest a selection scheme of 3D CT images that are
      respiratory-matched to each respiratory-gated sinogram. In this work, the
      proposed algorithm was evaluated qualitatively and quantitatively by using
      patient datasets including lung and/or liver lesion(s). Experimental results show
      that the method can provide much clearer organ boundaries and more accurate
      lesion information than existing algorithms by utilizing two low-dose CT images. 

PMID- 24077220
TI  - Role of matrix metalloproteinase-10 in the BMP-2 inducing osteoblastic
      differentiation.
AB  - Fibrodysplasia ossificans progressiva (FOP) is a skeletal disorder with
      progressive heterotopic ossification in skeletal muscle. A mutation causing
      constitutive activation in a bone morphogenetic protein (BMP) type 1 receptor
      [ALK2(R206H)] is found in most patients with FOP. However, the details in the
      heterotopic ossification of muscle in FOP and the role of matrix
      metalloproteinase-10 (MMP-10) in bone remain to be fully elucidated. In the
      present study, we investigated the role of MMP-10 in the differentiation of mouse
      myoblastic C2C12 cells into osteoblasts. MMP-10 was extracted as a factor, whose
      expression was most extensively enhanced by ALK2 (R206H) transfection in C2C12
      cells. MMP-10 significantly augmented the levels of Osterix, type 1 collagen,
      alkaline phosphatase (ALP) and osteocalcin mRNA as well as ALP activity enhanced
      by BMP-2 in C2C12 cells. Moreover, a reduction in endogenous MMP-10 levels by
      siRNA significantly decreased the levels of Runx2, Osterix, type 1 collagen, ALP
      and osteocalcin mRNA enhanced by BMP-2 in these cells. In addition, MMP-10
      increased the phosphorylation of Smad1/5/8 as well as enhanced the levels of
      Smad6 and Smad7 mRNA induced by BMP-2. In conclusion, the present study first
      demonstrated that MMP-10 promotes the differentiation of myoblasts into
      osteoblasts by interacting with the BMP signaling pathway. MMP-10 may play some
      important role in the heterotopic ossification of muscle in FOP. 

PMID- 24077221
TI  - Lymphatic drainage, regional metastases and surgical management of papillary
      thyroid carcinoma arising in pyramidal lobe--a single institution experience.
AB  - Papillary thyroid carcinoma (PTC) arising in pyramidal lobe (PL) is very rare.
      The aim of this study was to determine the incidence of single PTC focus in PL
      and its lymphonodal metastases, as well as to present a single surgeon experience
      in management of PL PTC. We performed a retrospective analysis of records of all
      patients surgically treated for PTC in our institution from year 2003 to 2013.
      Only patients with single PTC focus in PL were included. Out of total 753
      patients, majority (66.52%) had PTC focus in one of the lobes, while only 3
      patients (0.4%) had solitary PTC focus in PL. They were all females, aged 36, 41
      and 22. During surgery, methylene-blue dye was injected peritumorally. After
      frozen section analysis of excised PL and isthmus and confirmation of malignancy,
      we performed total thyroidectomy with central neck dissection, as well as
      sentinel lymph node biopsy in both jugulo-carotid regions. Pathology showed
      encapsulated PTC stage T1 and solitary metastasis in Delphian lymph node of the
      youngest patient. All patients were disease free in the follow-up. PTC single
      focus in PL is very rare and only individual experiences can be discussed
      regarding the extent of the surgery. 

PMID- 24077222
TI  - Prognosis of primary aldosteronism in Japan: results from a nationwide
      epidemiological study.
AB  - The Research Committee of Disorders of Adrenal Hormones, Japan, undertook a
      nationwide epidemiological study of primary aldosteronism (PA). The present study
      was undertaken as a part of this study to reveal the relationship between type of
      treatment and the prognosis of PA. In the primary survey, 4161 patients with PA
      during the period January 1, 2003-December 31, 2007 were reported from 3252
      departments of internal medicine, pediatrics and urology. In the secondary
      survey, a questionnaire that requested detailed clinical information on
      individual patients was sent to those departments reporting patients in the
      primary survey. In total, data on 1706 patients with PA were available in the
      present study. Among patients with bilateral or unilateral aldosterone-producing
      adenoma, after adjustment for age at which prognosis was examined, sex, surgical
      treatment and medical treatment, surgical treatment was significantly associated
      with amelioration of hypertension (adjusted odds ratio [OR]: 0.47 [95% confidence
      interval (CI): 0.29-0.77]) and hypokalemia (adjusted OR: 0.17 [95% CI: 0.11
      0.29]). No significant relationship was observed between medical treatment and
      such prognosis in this group of patients. Among patients with bilateral or
      unilateral adrenal hyperplasia, surgical, but not medical, treatment was
      significantly associated with amelioration of hypokalemia (adjusted OR: 0.23 [95%
      CI: 0.06-0.74]), while there was no relationship between surgical or medical
      treatment and the prognosis of hypertension. In conclusion, surgery offered a
      better prognosis of PA than medication with regards to hypertension and
      hypokalemia, with the limitation that a new anti-aldosterone drug, eplerenone,
      was not available during the study period. 

PMID- 24077223
TI  - Promiscuous RNA binding by Polycomb repressive complex 2.
AB  - Polycomb repressive complex 2 (PRC2) is a histone methyltransferase required for
      epigenetic silencing during development and cancer. Long noncoding RNAs (lncRNAs)
      recruit PRC2 to chromatin, but the general role of RNA in maintaining repressed
      chromatin is unknown. Here we measure the binding constants of human PRC2 to
      various RNAs and find comparable affinity for human lncRNAs targeted by PRC2 as
      for irrelevant transcripts from ciliates and bacteria. PRC2 binding is size
      dependent, with lower affinity for shorter RNAs. In vivo, PRC2 predominantly
      occupies repressed genes; PRC2 is also associated with active genes, but most of
      those are not regulated by PRC2. These findings support a model in which PRC2's
      promiscuous binding to RNA transcripts allows it to scan for target genes that
      have escaped repression, thus leading to maintenance of the repressed state. Such
      RNAs may also provide a decoy for PRC2. 

PMID- 24077224
TI  - Genome-wide analysis of A-to-I RNA editing by single-molecule sequencing in
      Drosophila.
AB  - The accurate and thorough genome-wide detection of adenosine-to-inosine editing,
      a biologically indispensable process, has proven challenging. Here, we present a
      discovery pipeline in adult Drosophila, with 3,581 high-confidence editing sites
      identified with an estimated accuracy of 87%. The target genes and specific sites
      highlight global biological properties and functions of RNA editing, including
      hitherto-unknown editing in well-characterized classes of noncoding RNAs and 645
      sites that cause amino acid substitutions, usually at conserved positions. The
      spectrum of functions that these gene targets encompass suggests that editing
      participates in a diverse set of cellular processes. Editing sites in Drosophila
      exhibit sequence-motif preferences and tend to be concentrated within a small
      subset of total RNAs. Finally, editing regulates expression levels of target
      mRNAs and strongly correlates with alternative splicing. 

PMID- 24077227
TI  - Coronary artery disease: an international disease-oriented journal.

PMID- 24077226
TI  - Divergent evolution of protein conformational dynamics in dihydrofolate
      reductase.
AB  - Molecular evolution is driven by mutations, which may affect the fitness of an
      organism and are then subject to natural selection or genetic drift. Analysis of
      primary protein sequences and tertiary structures has yielded valuable insights
      into the evolution of protein function, but little is known about the evolution
      of functional mechanisms, protein dynamics and conformational plasticity
      essential for activity. We characterized the atomic-level motions across
      divergent members of the dihydrofolate reductase (DHFR) family. Despite
      structural similarity, Escherichia coli and human DHFRs use different dynamic
      mechanisms to perform the same function, and human DHFR cannot complement DHFR
      deficient E. coli cells. Identification of the primary-sequence determinants of
      flexibility in DHFRs from several species allowed us to propose a likely scenario
      for the evolution of functionally important DHFR dynamics following a pattern of
      divergent evolution that is tuned by cellular environment. 

PMID- 24077228
TI  - Applications and limitations of cardiac computed tomography in the evaluation of
      coronary artery disease.
AB  - Cardiac computed tomography angiography (CCTA) has rapidly emerged in recent
      years as a promising noninvasive imaging modality for the evaluation of coronary
      artery disease. This is predominantly because of its proven ability to exclude
      coronary stenosis in patients without a history of coronary artery disease and
      with a low-intermediate pre-test likelihood. There is also increasing data on the
      utility of CCTA in risk stratification and assessment of prognosis. However, it
      is important to realize the shortcomings of the current technology before
      advocating its widespread use. Importantly, the utility of CCTA is limited when
      an abnormal study is anticipated. Because of current limitations on spatial and
      temporal resolution, CCTA cannot precisely assess the degree of stenosis as
      compared with invasive coronary angiography. This tendency of CCTA to
      overestimate stenosis severity along with its the poor positive predictive value
      can lead to increased downstream testing including additional stress testing and
      unnecessary invasive coronary angiography. Moreover, despite improvements in
      technology, the radiation burden of CCTA in real-world clinical practice remains
      significant. To justify greater use of CCTA in the current healthcare
      environment, future studies need to demonstrate improvements in patient outcomes,
      better accuracy compared with established tests, and/or reductions in healthcare
      costs. 

PMID- 24077225
TI  - Conformation and dynamics of the periplasmic membrane-protein-chaperone complexes
      OmpX-Skp and tOmpA-Skp.
AB  - The biogenesis of integral outer-membrane proteins (OMPs) in Gram-negative
      bacteria requires molecular chaperones that prevent the aggregation of OMP
      polypeptides in the aqueous periplasmic space. How these energy-independent
      chaperones interact with their substrates is not well understood. We have used
      high-resolution NMR spectroscopy to examine the conformation and dynamics of the
      Escherichia coli periplasmic chaperone Skp and two of its complexes with OMPs.
      The Skp trimer constitutes a flexible architectural scaffold that becomes more
      rigid upon substrate binding. The OMP substrates populate a dynamic
      conformational ensemble with structural interconversion rates on the
      submillisecond timescale. The global lifetime of the chaperone-substrate complex
      is seven orders of magnitude longer, emerging from the short local lifetimes by
      avidity. The dynamic state allows for energy-independent substrate release and
      provides a general paradigm for the conformation of OMP polypeptides bound to
      energy-independent chaperones. 

PMID- 24077229
TI  - Echocardiographic evaluation of coronary artery disease.
AB  - Although the availability and utilization of other noninvasive imaging modalities
      for the evaluation of coronary artery disease have expanded over the last decade,
      echocardiography remains the most accessible, cost-effective, and lowest risk
      imaging choice for many indications. The clinical utility of mature
      echocardiographic methods (i.e. two-dimensional echocardiography, stress
      echocardiography, contrast echocardiography) across the spectrum of coronary
      artery disease has been well established by numerous clinical studies. With
      continuing advancements in ultrasound technology, emerging ultrasound
      technologies such as three-dimensional echocardiography, tissue Doppler imaging,
      and speckle tracking methods hold significant promise to further widen the scope
      of clinical applications and improve diagnostic accuracy. In this review, we
      provide an update on the role of echocardiography in the diagnosis, management,
      and prognosis of coronary artery disease and introduce emerging technologies that
      are anticipated to further increase the clinical utility of echocardiography in
      the evaluation of patients with coronary artery disease. 

PMID- 24077230
TI  - Oxidation Kinetics and Magnetic Properties of Elemental Iron Nanoparticles.

PMID- 24077231
TI  - Impaired leaf CO2 diffusion mediates Cd-induced inhibition of photosynthesis in
      the Zn/Cd hyperaccumulator Picris divaricata.
AB  - Mechanisms of cadmium (Cd)-induced inhibition of photosynthesis in the Zn/Cd
      hyperaccumulator Picris divaricata were investigated using photosynthesis
      limitation analysis. P. divaricata seedlings were grown in nutrient solution
      containing 0, 5, 10, 25, 50, or 75 MUM Cd for 2 weeks. Total limitations to
      photosynthesis (TL) increased from 0% at 5 MUM Cd to 68.8% at 75 MUM Cd. CO2
      diffusional limitation (DL) made the largest contribution to TL, accounting for
      93-98% of TL in the three highest Cd treatments, compared to just 2-7% of TL
      attributable to biochemical limitation (BL). Microscopic imaging revealed
      significantly decreased stomatal density and mesophyll thickness in the three
      highest Cd treatments. Chlorophyll fluorescence parameters related to
      photosynthetic biochemistry (Fv/Fm, NPQ, PhiPSII, and qP) were not significantly
      decreased by increased Cd supply. Our results suggest that increased DL in leaves
      is the main cause of Cd-induced inhibition of photosynthesis in P. divaricata,
      possibly due to suppressed function of mesophyll and stomata. Analysis of
      chlorophyll fluorescence showed that Cd supply had little effect on
      photochemistry parameters, suggesting that the PSII reaction centers are not a
      main target of Cd inhibition of photosynthesis in P. divaricata. 

PMID- 24077232
TI  - Risk factors for comorbidities in Czech psoriatic patients: results of a hospital
      based case-control study.
AB  - BACKGROUND: Psoriasis is now known to be associated with multiple other
      diseases/comorbidities - including the metabolic syndrome, atherosclerosis and
      gastrointestinal diseases which are all significantly higher in psoriasis
      patients. Research results however are highly variable and the conclusions are
      ambiguous. As no similar study has been performed to date in Czech psoriatic
      patients, this study aimed at identifying risk factors and early stages of
      selected diseases/comorbidities in the patients. METHODS AND RESULTS: The study
      was designed as a hospital-based case-control study. 131 patients with chronic
      plaque psoriasis formed the cases and 267 patients with other skin disorders
      formed the controls. A comparison was made of basic demographic and
      anthropometric indicators, metabolic parameters, the presence of specific
      antibodies (ASCA, AEP, p-ANCA, AGC, EMA, ARA, t-TG, AGA) and non-specific signs
      of gastrointestinal diseases. The chi squared, MWU tests and binary logistical
      model were used to evaluate the data. The results showed significant differences
      (P<0.05) for the following parameters: blood pressure, waist circumference,
      weight, BMI values, leucocytes values, HDL cholesterol level, glycemia and
      gliadine antibody IgA level. All differences were to the detriment of psoriasis
      patients. In the binary logistical model the following parameters were associated
      with psoriasis: diastolic blood pressure, leucocyte value and glycemia. For all
      variables included in the logistical model P<=0.001. CONCLUSIONS: The results
      were coherent and consistent with existing data. They indicate that psoriasis is
      interconnected with hypertension, higher BMI and a decreased level of HDL
      cholesterol. These parameters have been clearly demonstrated as risk factors for
      the development of cardiovascular diseases. Higher levels of gliadine IgA
      antibodies are one of the diagnostic markers of celiac disease. Higher values of
      leukocytes may be interpreted as a nonspecific indicator of gastrointestinal
      inflammatory diseases. The associations between psoriasis and diastolic blood
      pressure, BMI value and glycemia are statistically significant in the binary
      logistic regression model. Care for psoriatic patients should focus especially on
      secondary prevention of predisposing diseases.

PMID- 24077233
TI  - Pediatric parotideomasseteric pilomatrixoma in children.
AB  - AIMS: To review definitive histological diagnoses of patients with great salivary
      gland tumors with focus on the relatively high incidence of pediatric
      pilomatrixomas. The authors focus on clinical investigation, imaging methods and
      fine needle aspiration cytology of pilomatrixomas. METHODS: We treated 12
      children with great salivary gland masses aged from 6 months to 18 years from
      1995 to 2010. The records of these patients were reviewed to determine sex, age,
      clinical presentation, and histological findings. RESULTS: Among children having
      true neoplasms, there was a prevalence of carcinomas (6 out of 9), with low-grade
      mucoepidermoid and acinic cell carcinomas (two each) as the dominating
      histopathological diagnosis. There was one adenoid cystic carcinoma and one
      curious undifferentiated carcinoma in a 6 month old baby. Among all 6 benign
      lesions, accounting for a half of the total, pilomatrixoma was the most common (2
      out of 6) diagnosis, representing 17% (2 out of 12) of all salivary gland lumps
      and 66% (2 out of 3) of all true benign neoplasms. CONCLUSIONS: Pilomatrixoma
      should be included in the differential diagnosis of pediatric parotideomasseteric
      lumps. Clinical investigation reveals adherence to the skin but not to the
      underlying tissue. Clinical assessment and ultrasound guided fine needle
      aspiration cytology in typical findings strongly support the diagnosis.
      Cytopathologists must be aware of the preliminary diagnosis of a pilomatrixoma to
      use proper fixation of the smears. In doubts, frozen biopsy must be sent before
      parotidectomy is performed.

PMID- 24077234
TI  - The relationship between renal cell carcinoma and nuclear retinoid/rexinoid
      receptors.
AB  - BACKGROUND: Renal cell carcinoma (RCC) is a urologic malignancy with a steady
      rise in incidence and high mortality rate. Between 60 to 70% of patients with
      renal cell carcinoma can only be cured with surgery but despite advances in early
      diagnostis, in around 20-30% of cases there is metastasis. For these patients,
      chemotherapy and radiotherapy are ineffective and hence the prognosis is poor.
      Retinoids are biologically active compounds of either natural or synthetic origin
      that are involved in complex physiological and developmental processes in many
      tissues including cell proliferation and activation of tumour suppression genes.
      This article reviews the role of retinoids and their cognate nuclear
      retinoid/rexinoid receptors in relation to renal cell carcinoma. METHODS: A
      literature search using ScienceDirect and Medline with a focus on the
      relationship between renal cell carcinoma and nuclear retinoid/rexinoid
      receptors. RESULTS: Use of retinoids/rexinoids in the treatment of locally
      advanced and metastatic RCC significantly prolongs median time of tumour
      progression and overall survival of patients. Combination therapy with other
      preparations has greater efficacy than treatment with retinoids alone. Patient
      survival can be predicted on the basis of the expression of different all-trans
      retinoic acid receptor (RAR) and 9-cis retinoic acid receptor (RXR) subtypes.
      CONCLUSIONS: Since nuclear retinoid receptors play a crucial role as ligand
      activated, DNA binding, trans-acting, transcription-modulating proteins involved
      in a general molecular mechanism responsible for transcriptional responses in
      target genes, retinoids might be an alternative approach for the treatment of
      renal cell carcinoma.

PMID- 24077235
TI  - In vitro testing of immunosupressive effects of mesenchymal stromal cells on
      lymphocytes stimulated with alloantigens.
AB  - AIMS: Mesenchymal stromal cells (MSC) derived from adult bone marrow or adipose
      tissue offer the potential to open a new frontier in medicine. MSC are involved
      in modulating immune response and tissue repair in vitro and in vivo.
      Experimental evidence and preliminary clinical studies have demonstrated that MSC
      exhibit an important immunomodulatory function in patients with graft versus host
      disease (GVHD) following allogeneic hematopoietic stem cell transplantation. The
      immunosuppressive properties of MSC have already been exploited in the clinical
      setting. However the precise mechanisms are being still investigated. METHODS: We
      examined the immunosuppressive function of MSC by coculturing them with
      stimulated HLA incompatible allogeneic lymphocytes in a mixed lymphocyte culture
      test. The metabolic and proliferative activity of lymphocytes was determined by
      MTT test. RESULTS: After stimulation with alloantigens the presence of MSC caused
      significant decrease of absorbance levels by 62% (P<0.01), 26% (P<0.01) and 6%
      (P=0.0437) in comparison to positive control depending on the MSC/lymphocyte
      ratio (1:5, 1:50, 1:500). The mitogenic stimulation of lymphocytes with fMLP or
      PHA was also significantly reduced during MSC cocultivation. The absorbance was
      reduced by 42% (P<0.001) and 67% (P<0.001). CONCLUSIONS: Allogeneic bone marrow
      is an ideal source of MSC for clinical application. The experiments confirmed the
      dose-dependent inhibitory effect of MSC on lymphocyte proliferation triggered by
      cellular or mitogenic stimulation. The mixed lymphocyte culture test offers a
      simple method for characterization and verification of the immunosuppressive
      potential of MSC, being prepared for clinical use.

PMID- 24077236
TI  - Amniotic fluid embolism--investigation of fatal cases in Slovakia in the years
      2005-2010 compared with fatal cases in the United Kingdom.
AB  - BACKGROUND: Amniotic fluid embolism (AFE) is a rare, often severe complication of
      pregnancy. The clinical diagnosis is difficult to establish and is one of
      exclusion. The aim of this study was to investigate 6 fatal cases of AFE in
      Slovakia and compare the incidence, risk factors, course, management and neonatal
      outcomes with fatal cases of AFE in the United Kingdom (UK). MATERIALS AND
      METHODS: Data on fatal cases of AFE in Slovakia were analysed and compared with
      fatal cases in the UK in the years 2005-2010. RESULTS: The incidence in Slovakia
      was significantly higher than in the UK from 2005-2010 (RR 5.03, 95% CI 1.98
      12.75, P=0.003). However, 5/6 deaths occurred in 2009 coinciding with the H1N1
      flu virus pandemic in Slovakia. There were no significant differences in the
      characteristics of women who died, with the exception of gestational age at
      delivery; significantly higher in Slovakia (median 41 versus 39 weeks, P=0.01).
      In Slovakia most of the cases occurred after delivery, 83.3%, compared with 52.9%
      in the UK. There were no significant differences in clinical signs, use of
      recombinant factor VIIa or performance of obstetric hysterectomy. In Slovakia
      83.3% and in the UK 94.7% of infants survived, but 20% and 27.8% had some long
      term sequelae. CONCLUSION: AFE is now the leading cause of maternal deaths in
      Slovakia. However, we found no significant differences in the possible risk
      factors, course, management or outcomes between Slovakia and the UK. This
      analysis is limited by study power; we propose that establishment of a national
      register of cases of AFE in Slovakia would help further investigate and monitor
      mortality from this condition.

PMID- 24077238
TI  - An instrument to measure adherence to weight loss programs: the compliance praxis
      survey-diet (COMPASS-Diet).
AB  - Adherence to behavioral weight loss strategies is important for weight loss
      success. We aimed to examine the reliability and validity of a newly developed
      compliance praxis-diet (COMPASS-diet) survey with participants in a 10-week
      dietary intervention program. During the third of five sessions, participants of
      the "slim-without-diet" weight loss program (n = 253) completed the COMPASS-diet
      survey and provided data on demographic and clinical characteristics, and general
      self-efficacy. Group facilitators completed the COMPASS-diet-other scale
      estimating participants' likely adherence from their perspective. We calculated
      internal consistency, convergent validity, and predictive value for objectively
      measured weight loss. Mean COMPASS-diet-self score was 82.4 (SD 14.2) and COMPASS
      diet-other score 80.9 (SD 13.6) (possible range 12-108), with lowest scores in
      the normative behavior subscale. Cronbach alpha scores of the COMPASS-diet-self
      and -other scale were good (0.82 and 0.78, respectively). COMPASS-diet-self
      scores (r = 0.31) correlated more highly with general self-efficacy compared to
      COMPASS-diet-other scores (r = 0.04) providing evidence for validity. In
      multivariable analysis adjusted for age and gender, both the COMPASS-diet-self (F
      = 10.8, p < 0.001, r2 = 0.23) and other (F = 5.5, p < 0.001, r2 = 0.19) scales
      were significantly associated with weight loss achieved at program conclusion.
      COMPASS-diet surveys will allow group facilitators or trainers to identify
      patients who need additional support for optimal weight loss.

PMID- 24077239
TI  - Non-Celiac Gluten sensitivity: the new frontier of gluten related disorders.
AB  - Non Celiac Gluten sensitivity (NCGS) was originally described in the 1980s and
      recently a "re-discovered" disorder characterized by intestinal and extra
      intestinal symptoms related to the ingestion of gluten-containing food, in
      subjects that are not affected with either celiac disease (CD) or wheat allergy
      (WA). Although NCGS frequency is still unclear, epidemiological data have been
      generated that can help establishing the magnitude of the problem. Clinical
      studies further defined the identity of NCGS and its implications in human
      disease. An overlap between the irritable bowel syndrome (IBS) and NCGS has been
      detected, requiring even more stringent diagnostic criteria. Several studies
      suggested a relationship between NCGS and neuropsychiatric disorders,
      particularly autism and schizophrenia. The first case reports of NCGS in children
      have been described. Lack of biomarkers is still a major limitation of clinical
      studies, making it difficult to differentiate NCGS from other gluten related
      disorders. Recent studies raised the possibility that, beside gluten, wheat
      amylase-trypsin inhibitors and low-fermentable, poorly-absorbed, short-chain
      carbohydrates can contribute to symptoms (at least those related to IBS)
      experienced by NCGS patients. In this paper we report the major advances and
      current trends on NCGS. 

PMID- 24077240
TI  - Cocoa and heart health: a historical review of the science.
AB  - The medicinal use of cocoa has a long history dating back almost five hundred
      years when Hernan Cortes's first experienced the drink in Mesoamerica. Doctors in
      Europe recommended the beverage to patients in the 1700s, and later American
      physicians followed suit and prescribed the drink in early America--ca. 1800s.
      This article delineates the historic trajectory of cocoa consumption, the linkage
      between cocoa's bioactive-mechanistic properties, paying special attention to
      nitric oxides role in vasodilation of the arteries, to the current indicators
      purporting the benefits of cocoa and cardiovascular health.

PMID- 24077241
TI  - Dietary factors and type 2 diabetes in the Middle East: what is the evidence for
      an association?--a systematic review.
AB  - This review aims to search and summarise the available evidence on the
      association between dietary factors and type 2 diabetes mellitus (T2DM) in Middle
      Eastern populations, where diabetes prevalence is among the highest in the world.
      Electronic databases were searched; authors, libraries, and research centres in
      the Middle East were contacted for further studies and unpublished literature.
      Included studies assessed potential dietary factors for T2DM in Middle Eastern
      adults. Two reviewers assessed studies independently. Extensive searching yielded
      17 studies which met the inclusion criteria for this review. The findings showed
      that whole-grain intake reduces the risk of T2DM, and potato consumption was
      positively correlated with T2DM. Vegetables and vegetable oil may play a
      protective role against T2DM. Dietary patterns that are associated with diabetes
      were identified, such as Fast Food and Refined Grains patterns. Two studies
      demonstrated that lifestyle interventions decreased the risk of T2DM. In summary,
      the identified studies support an association between some dietary factors and
      T2DM; however, many of the included studies were of poor methodological quality
      so the findings should be interpreted with caution. The review draws attention to
      major gaps in current evidence and the need for well-designed studies in this
      area. 

PMID- 24077242
TI  - The unappreciated importance of blood pressure in recent and older atrial
      fibrillation trials.
AB  - Atrial fibrillation and arterial hypertension represent two common clinical
      conditions that frequently coexist, especially in older individuals, and are
      associated with increased risk of stroke. Antihypertensive therapy reduces the
      risk of stroke by approximately 40%. It has been observed that stroke rates were
      reduced by 10% for every 2-mmHg reduction of blood pressure. Antithrombotic
      therapy reduces significantly the risk for ischemic stroke in patients with
      atrial fibrillation at the expense of increased risk of intracranial bleeding.
      The importance of hypertension in patients with atrial fibrillation is recognized
      by its inclusion both in the CHA2DS2-VASc (risk for stroke) and the HAS-BLED
      (Hypertension, Abnormal renal/liver function, Stroke, Bleeding history or
      predisposition, Labile international normalized ratio, Elderly, Drugs/alcohol
      concomitantly) scores (risk for bleeding) and the presence of hypertension alone
      is an indication to initiate antithrombotic treatment. However, blood pressure
      remains remarkably unappreciated in previous and recent atrial fibrillation
      trials. Very limited, if any, data are provided regarding blood pressure,
      including in-study and final blood pressure levels, blood pressure control, and
      concomitant antihypertensive medication. In contrast, several lines of evidence
      point toward a significant role of pre and in-treatment blood pressure for
      ischemic and hemorrhagic stroke in patients with atrial fibrillation as well as
      for the incidence of intracranial bleeding during antithrombotic treatment. We
      propose that regular blood pressure recording should be mandatory in all future
      studies with antithrombotic therapy, analyses based on final and in-study blood
      pressure values, hypertension control, and antihypertensive medication should be
      performed, and the outcome be adjusted for blood pressure-related variables. 

PMID- 24077237
TI  - Polyphenols: benefits to the cardiovascular system in health and in aging.
AB  - Numerous studies have demonstrated the importance of naturally occurring dietary
      polyphenols in promoting cardiovascular health and emphasized the significant
      role these compounds play in limiting the effects of cellular aging. Polyphenols
      such as resveratrol, epigallocatechin gallate (EGCG), and curcumin have been
      acknowledged for having beneficial effects on cardiovascular health, while some
      have also been shown to be protective in aging. This review highlights the
      literature surrounding this topic on the prominently studied and documented
      polyphenols as pertaining to cardiovascular health and aging. 

PMID- 24077243
TI  - Interventional hypertension: a new hope or a new hype? The need to redefine
      resistant hypertension.

PMID- 24077244
TI  - A new, accurate predictive model for incident hypertension.
AB  - OBJECTIVE: Data mining represents an alternative approach to identify new
      predictors of multifactorial diseases. This work aimed at building an accurate
      predictive model for incident hypertension using data mining procedures. METHODS:
      The primary study population consisted of 1605 normotensive individuals aged 20
      79 years with 5-year follow-up from the population-based study, that is the Study
      of Health in Pomerania (SHIP). The initial set was randomly split into a training
      and a testing set. We used a probabilistic graphical model applying a Bayesian
      network to create a predictive model for incident hypertension and compared the
      predictive performance with the established Framingham risk score for
      hypertension. Finally, the model was validated in 2887 participants from INTER99,
      a Danish community-based intervention study. RESULTS: In the training set of SHIP
      data, the Bayesian network used a small subset of relevant baseline features
      including age, mean arterial pressure, rs16998073, serum glucose and urinary
      albumin concentrations. Furthermore, we detected relevant interactions between
      age and serum glucose as well as between rs16998073 and urinary albumin
      concentrations [area under the receiver operating characteristic (AUC 0.76)]. The
      model was confirmed in the SHIP validation set (AUC 0.78) and externally
      replicated in INTER99 (AUC 0.77). Compared to the established Framingham risk
      score for hypertension, the predictive performance of the new model was similar
      in the SHIP validation set and moderately better in INTER99. CONCLUSION: Data
      mining procedures identified a predictive model for incident hypertension, which
      included innovative and easy-to-measure variables. The findings promise great
      applicability in screening settings and clinical practice.

PMID- 24077245
TI  - Differences between office and ambulatory blood pressures in children and
      adolescents attending a hospital hypertension clinic.
AB  - BACKGROUND AND OBJECTIVES: Information on ambulatory blood pressure monitoring
      (ABPM) in children is scarce. While in adults office BP (OBP) is higher than ABP
      and the difference increases as OBP increases, information in children suggests
      that at this young age ABP is no lower and often higher than OBP. This study was
      aimed at describing OBP-ABP differences in a cohort of children of different ages
      and BPs, and investigating whether OBP-ABP differences are dependent on age or
      OBP level. METHODS: We retrospectively compared OBP and 24-h, daytime and night
      time ABP in 433 children and adolescents aged 4-18 years, referred to our
      hospital clinic. RESULTS: OBP was found to be significantly lower than 24-h and
      daytime ABP in the low age tertile (4-10 years) but not in the medium and high
      tertiles. OBP was also lower than ABP in normotensive patients (n = 182), but
      higher than ABP in untreated hypertensive patients (n = 92) despite similar ages.
      Continuous analyses showed a weak correlation of OBP-ABP differences with age,
      and a much stronger correlation with OBP so that 24-h ABP was higher than OBP at
      OBP values less than 117/73 mmHg and lower than OBP at higher OBP values.
      Logistic regression analysis indicates that also in children OBP accounts for
      most of the OBP-ABP difference. CONCLUSION: There is a common relation both in
      children and adults between OBP and ABP. It is only because high OBP is common in
      the elderly, and the lowest OBP is usually found in young children that large
      positive OBP-ABP differences have been associated with old age, and negative
      differences with childhood. OBP-ABP differences, often defined as white-coat
      effect, can have different directions and are likely to be largely due to
      regression to the mean.

PMID- 24077246
TI  - Carotid-femoral pulse wave velocity assessment using novel cuff-based techniques:
      comparison with tonometric measurement.
AB  - BACKGROUND: Carotid-femoral pulse wave velocity, a predictor of cardiovascular
      outcome, is conventionally measured using a tonometer sequentially placed upon
      the carotid and femoral arteries, gated using an electrocardiogram. Leg cuff
      detection of the femoral pulse removes the need for signal gating, reduces the
      time required for a single measurement, but gives different pulse wave velocity
      values to tonometric analysis. A novel algorithm to correct for the transit time
      and distance related to the additional femoral segment was applied to the cuff
      based approach in this study. METHOD: Eighty-eight individuals were recruited
      across four centres and carotid-femoral pulse wave velocity measured in
      triplicate using two operators with both a tonometer-based device and a device
      using an inflated thigh cuff with and without the use of the novel algorithm.
      Comparison was made by Bland-Altman and regression analysis. RESULTS: The
      unadjusted cuff-based approach gave lower pulse wave velocity values than the
      tonometer-based approach (6.11 +/- 1.27 and 7.02 +/- 1.88 m/s, P < 0.001). With
      application of the algorithm, the cuff-based device gave similar pulse wave
      velocity values (7.04 +/- 1.72 m/s) as the tonometer-based approach (P = 0.86).
      Analysis of covariance with age showed a difference between the tonometer and
      cuff-based methods (P < 0.001), with a dependence upon age (P = 0.004). The
      adjusted cuff-based method gave similar results to the tonometer-based method (P
      = 0.94), with no dependence upon age (P = 0.46). CONCLUSION: This study provided
      validation of a cuff-based assessment of carotid-femoral pulse wave velocity
      against the universally accepted tonometric method. Adjusting the cuff-based
      method for the additional femoral segment measured gives results comparable to
      the tonometer-based method, for which the majority of population data exist to
      date.

PMID- 24077247
TI  - Angiotensin-II induced hypertension and renovascular remodelling in tissue
      inhibitor of metalloproteinase 2 knockout mice.
AB  - BACKGROUND: Sustained hypertension induces renovascular remodelling by altering
      extracellular matrix (ECM) components. Matrix metalloproteinases (MMPs) are Zn
      dependent enzymes that regulate ECM turnover in concert with their inhibitors,
      tissue inhibitors of metalloproteinases (TIMPs). Increased MMP-2 and MMP-9 have
      been implicated in hypertensive complications; however, the contribution of
      individual MMPs/TIMPs in renal remodelling has not been fully elucidated. The
      purpose of this study was to determine the effect of TIMP2 deficiency and thus
      MMP-2 on angiotensin-II (Ang-II) induced renal remodelling. METHOD: C57BL/6J
      (wild-type) and TIMP2 knockout mice were infused with Ang-II at 250 ng/kg per min
      for 4 weeks. Blood pressure was measured weekly and end-point laser Doppler
      flowmetry was done to assess cortical blood flow. Immunohistochemical staining
      was performed for collagen and elastin analyses. The activity of MMP-9 and MMP-2
      was determined by Gelatin zymography. RESULTS: Ang-II induced similar elevation
      in mean blood pressure in TIMP2 and wild-type mice. In TIMP2 mice, Ang-II
      treatment was associated with a greater reduction in renal cortical blood flow
      and barium angiography demonstrated decreased vascular density compared with Ang
      II treated wild-type mice. Peri-glomerular and vascular collagen deposition was
      increased and elastin content was decreased causing increased wall-to-lumen ratio
      in TIMP2 mice compared with wild-type mice receiving Ang-II. Ang-II increased the
      expression and activity of MMP-9 predominantly in TIMP2 mice than in wild-type
      mice. CONCLUSION: These results suggest that TIMP2 deficiency exacerbates
      renovascular remodelling in agonist-induced hypertension by a mechanism that may,
      in part, be attributed to increased activity of MMP-9.

PMID- 24077248
TI  - Effects of sex and hypertension subtype on haemodynamics and left ventricular
      diastolic function in older patients with stage 1 hypertension.
AB  - BACKGROUND: Hypertension is associated with cardiovascular stiffening and left
      ventricular diastolic dysfunction, leading to comorbidities such as heart failure
      with preserved ejection fraction (HFpEF). It is unknown whether sex and
      hypertension subtype affect haemodynamics and left ventricular function in older
      individuals. METHODS: Ninety-five older patients with Stage 1 hypertension
      (ambulatory awake SBP135-159 mmHg) and 56 normotensive controls were enrolled.
      Patients were stratified prospectively into isolated systolic hypertension (ISH,
      DBP <85 mmHg) or systolic-diastolic hypertension (SDH, DBP >=85 mmHg).
      Haemodynamics and Doppler variables including early filling (E) and averaged
      mitral annular (E'mean) velocities were measured during supine rest. RESULTS:
      Ambulatory awake blood pressures (BPs) were the highest in SDH, whereas supine
      SBP was similar in both hypertensive groups. No sex difference was observed in
      supine or ambulatory awake BPs in all groups. Stroke volume was similar among
      groups within the same sex, but smaller in women. Women exhibited faster E,
      slower E'mean and greater E/E'mean, whereas no group difference was observed in E
      within the same sex. In women, E'mean was significantly slower in SDH (5.9 +/-
      1.6 vs. 7.4 +/- 1.1 cm/s, P < 0.01) and ISH (6.6 +/- 1.6 cm/s, P = 0.07) than
      controls, resulting in the highest E/E'mean in SDH. In men, E'mean and E/E'mean
      were similar among the three groups. CONCLUSION: These results suggest that
      elderly hypertensive women may have left ventricular early diastolic dysfunction
      and higher estimated filling pressure, consistent with their susceptibility to
      HFpEF. Women with SDH seemed to have more left ventricular diastolic dysfunction,
      which might be explained by the greater cumulative afterload when ambulatory.

PMID- 24077249
TI  - Effects of telmisartan and linagliptin when used in combination on blood pressure
      and oxidative stress in rats with 2-kidney-1-clip hypertension.
AB  - OBJECTIVE: To investigate the effects of linagliptin alone and in combination
      with the angiotensin II receptor blocker (ARB), telmisartan on blood pressure
      (BP), kidney function, heart morphology and oxidative stress in rats with
      renovascular hypertension. METHODS: Fifty-seven male Wistar rats underwent
      unilateral surgical stenosis of the renal artery [2-kidney-1-clip (2k1c) method].
      Animals were randomly divided into four treatment groups (n = 14-18 per group)
      receiving: telmisartan (10 mg/kg per day in drinking water), linagliptin (89 ppm
      in chow), combination (linagliptin 89 ppm + telmisartan 10 mg/kg per day) or
      placebo. An additional group of 12 rats underwent sham surgery. BP was measured
      one week after surgery. Hypertensive animals entered a 16-week dosing period. BP
      was measured 2, 4, 8, 12 and 16 weeks after the initiation of treatment. Blood
      and urine were tested for assessment of kidney function and oxidative stress 6,
      10, 14 and 18 weeks after surgery. Blood and urine sampling and organ harvesting
      were finally performed. RESULTS: Renal stenosis caused an increase in mean +/- SD
      systolic BP as compared with the sham group (157.7 +/- 29.3 vs. 106.2 +/- 20.5
      mmHg, respectively; P < 0.001). Telmisartan alone and in combination with
      linagliptin, normalized SBP (111.1 +/- 24.3 mmHg and 100.4 +/- 13.9 mmHg,
      respectively; P < 0.001 vs. placebo). Telmisartan alone and in combination with
      linagliptin significantly prevented cardiac hypertrophy, measured by heart weight
      and myocyte diameter. Renal function measured by cystatin C was not affected by
      2k1c surgery. Telmisartan significantly increased plasma concentration of
      cystatin C. 2k1c surgery initiated fibrosis in both kidneys. Telmisartan promoted
      further fibrotic changes in the clipped kidney, as measured by protein expression
      of Col1a1 and histology for interstitial fibrosis and glomerulosclerosis. In non
      clipped kidneys, telmisartan demonstrated antifibrotic properties, reducing
      Col1a1 protein expression. Plasma levels of oxidized low-density lipoprotein were
      higher in the placebo-treated 2k1c rats as compared to sham-operated animals. The
      increase was abolished by linagliptin alone (P = 0.03 vs. placebo) and in
      combination with telmisartan (P = 0.02 vs. placebo). Combination therapy also
      significantly reduced plasma concentration of carbonyl proteins (P = 0.04 vs.
      placebo). CONCLUSION: Inhibition of type 4 dipeptidyl peptidase with linagliptin
      did not counter BP-lowering effects of ARB in 2k1c rats. Linagliptin reduced
      lipid and protein oxidation in 2k1c rats, and this effect was BP-independent.

PMID- 24077250
TI  - Eplerenone enhances cardioprotective effects of standard heart failure therapy
      through matricellular proteins in hypertensive heart failure.
AB  - AIMS: The addition of an aldosterone receptor antagonist on top of current
      optimal therapy (based on angiotensin II inhibition) has demonstrated an
      important clinical benefit in heart failure patients with systolic dysfunction.
      Whether this finding also applies to heart failure patients with preserved
      systolic function is unknown. Therefore, we have studied the effect of adding
      eplerenone to standard pharmacological heart failure therapy (angiotensin
      converting enzyme inhibitor/angiotensin receptor blocker and diuretic and beta
      blocker) in the progression of heart failure in spontaneously hypertensive heart
      failure (SHHF) rats. METHODS AND RESULTS: Two-month-old SHHF rats were randomized
      to receive no treatment (SHHF group), a standard heart failure therapy (quinapril
      torasemide-carvedilol; ST-SHHF group), or the combination of eplerenone and
      standard heart failure therapy (Eple+ST-SHHF group) for 20 months. Untreated SHHF
      was characterized by progressive left ventricular hypertrophy, fibrosis, and
      myocardial contractile and relaxation abnormalities, leading to pulmonary
      congestion. Despite similar blood pressure control, the addition of eplerenone to
      standard heart failure therapy further prevented left ventricular hypertrophy,
      contractile and relaxation alterations, and pulmonary congestion than standard
      heart failure therapy alone. ST-SHHF and Eple + ST-SHHF rats showed similar
      inhibition of structural extracellular matrix proteins collagen I, collagen III
      and fibronectin and metalloproteinase (MMP)-2, MMP-7, MMP-12, and MMP-13.
      However, only the coadministration of eplerenone with standard heart failure
      therapy normalized the expression of matricellular proteins thrombospondin 1,
      tenascin C, periostin, and secreted protein acidic rich in cysteine/osteonectin
      to values comparable to normotensive rats. CONCLUSION: In a hypertensive heart
      failure rat model, the addition of eplerenone to conventional heart failure
      therapy further improves cardiac structural and functional parameters, delaying
      the progression of heart failure. These beneficial effects of eplerenone were
      associated with normalization of matricellular protein expression.

PMID- 24077251
TI  - Phylogenomic analysis of Cation Diffusion Facilitator proteins uncovers Ni2+/Co2+
      transporters.
AB  - The ubiquitous Cation Diffusion Facilitator proteins (CDF) play a key role in
      maintaining the cellular homeostasis of essential metal ions. Previous neighbor
      joining phylogenetic analysis classified CDF proteins into three substrate
      defined groups: Zn(2+), Fe(2+)/Zn(2+) and Mn(2+). These studies were unable to
      discern substrate-defined clades for Ni(2+), Co(2+), Cd(2+) and Cu(2+)
      transporters, despite their existence in this family. In this study we improved
      the accuracy of this previous functional classification using a phylogenomic
      approach based on a thorough maximum-likelihood phylogeny and the inclusion of
      recently characterized CDF transporters. The inference of CDF protein function
      predicted novel clades for Zn(2+), Fe(2+), Cd(2+) and Mn(2+). The Ni(2+)/Co(2+)
      and Co(2+) substrate specificities of two clades containing uncharacterized
      proteins were defined through the functional characterization of nepA and cepA
      metal inducible genes which independently conferred Ni(2+) and Co(2+) resistances
      to Rhizobium etli CFN42 and increased, respectively, Ni(2+)/Co(2+) and Co(2+)
      resistances to Escherichia coli. Neither NepA nor CepA confer Zn(2+), Fe(2+) and
      Mn(2+) resistances. The ability of NepA to confer Ni(2+)/Co(2+) resistance is
      dependent on clade-specific residues Asn(88) and Arg(197) whose mutations produce
      a non-functional protein.

PMID- 24077253
TI  - Bioaccumulation and trophic transfer of perfluorinated compounds in a eutrophic
      freshwater food web.
AB  - In this study, the bioaccumulation of perfluorinated compounds from a food web in
      Taihu Lake in China was investigated. The organisms included egret bird species,
      carnivorous fish, omnivorous fish, herbivorous fish, zooplankton, phytoplankton,
      zoobenthos and white shrimp. Isotope analysis by delta(13)C and delta(15)N
      indicated that the carnivorous fish and egret were the top predators in the
      studied web, occupying trophic levels intermediate between 3.66 and 4.61, while
      plankton was at the lowest trophic level. Perfluorinated carboxylates (PFCAs)
      with 9-12 carbons were significantly biomagnified, with trophic magnification
      factors (TMFs) ranging from 2.1 to 3.7. The TMF of perfluorooctane sulfonate
      (PFOS) (2.9) was generally comparable to or lower than those of the PFCAs in the
      same food web. All hazard ratio (HR) values reported for PFOS and
      perfluorooctanoate (PFOA) were less than unity, suggesting that the detected
      levels would not cause any immediate health effects to the people in Taihu Lake
      region through the consumption of shrimps and fish.

PMID- 24077252
TI  - Obstructive lung disease in Mexican Americans and non-Hispanic whites: an
      analysis of diagnosis and survival in the National Health and Nutritional
      Examination Survey III Follow-up Study.
AB  - BACKGROUND: Although obstructive lung disease (OLD), which includes COPD, affects
      all the populations, Hispanics seem to be protected against COPD development and
      progression. Whether this advantage translates into a survival benefit for this
      population is unknown. We aimed to determine the risk for OLD in Mexican
      Americans, the largest US Hispanic subgroup, compared with non-Hispanic whites
      and to assess all-cause mortality in subjects with OLD. METHODS: We assessed the
      relationships between Mexican American ethnicity and spirometric OLD and risk of
      death among 6,456 US adults aged >= 40 years who participated in the Third
      National Health and Nutritional Examination Survey Follow-up Study. We used
      logistic and Cox regression analyses to estimate the OR for OLD among Mexican
      Americans and the hazard ratio (HR) for all-cause mortality among Mexican
      Americans with OLD, respectively. RESULTS: After adjustment for demographic
      factors, socioeconomic status, and COPD risk factors, Mexican Americans had
      decreased odds of OLD diagnosis compared with whites (OR, 0.72 [95% CI, 0.54
      0.95]). Among the 1,734 participants with OLD, 1,054 (60.8%) died during median
      follow-up of 12 years. In an adjusted model, Mexican Americans had no advantage
      in mortality from all causes (HR, 0.88 [95% CI, 0.69-1.13]). After accounting for
      the fact that some Mexican Americans may have moved back to Mexico and died there
      (thus, had no US death certificate), there was still no difference in mortality
      between these groups. CONCLUSIONS: Although Mexican Americans appear to have
      lower risk for OLD, subjects of this ethnicity with OLD do not seem to have a
      survival advantage.

PMID- 24077254
TI  - Occurrence of phthalic acid esters in source waters: a nationwide survey in China
      during the period of 2009-2012.
AB  - The first nationwide survey of six phthalic acid esters (PAEs) (diethyl phthalate
      (DEP); dimethyl phthalate (DMP); di-n-butyl phthalate (DBP); butyl benzyl
      phthalate (BBP); bis(2-ethylhexyl) phthalate (DEHP); di-n-octyl phthalate (DnOP))
      in source waters was conducted in China. The results showed these PAEs were
      ubiquitous in source waters. DBP and DEHP were the most frequently detected with
      high concentrations ranging nd-1.52 MUg/L and nd-6.35 MUg/L, respectively. These
      PAEs concentrations (except DBP) in surface water (rivers, lakes and reservoirs)
      were generally higher than those in groundwater; DBP had high concentrations in
      groundwater in Northeast China (Liao River Basin) and North China (Hai River
      Basin). Their concentrations in the northern regions were generally higher than
      those in the southern and eastern regions; particularly, in North China. Three
      short-chain PAEs (DMP, DEP and DBP) were detected with high concentrations in Hai
      River Basin, Pearl River Basin and Yellow River Basin. 

PMID- 24077255
TI  - Predicting nitrogen and acidity effects on long-term dynamics of dissolved
      organic matter.
AB  - Increases in dissolved organic carbon (DOC) fluxes may relate to changes in
      sulphur and nitrogen pollution. We integrated existing models of vegetation
      growth and soil organic matter turnover, acid-base dynamics, and organic matter
      mobility, to form the 'MADOC' model. After calibrating parameters governing
      interactions between pH and DOC dissolution using control treatments on two field
      experiments, MADOC reproduced responses of pH and DOC to additions of acidifying
      and alkalising solutions. Long-term trends in a range of acid waters were also
      reproduced. The model suggests that the sustained nature of observed DOC
      increases can best be explained by a continuously replenishing potentially
      dissolved carbon pool, rather than dissolution of a large accumulated store. The
      simulations informed the development of hypotheses that: DOC increase is related
      to plant productivity increase as well as to pH change; DOC increases due to
      nitrogen pollution will become evident, and be sustained, after soil pH has
      stabilised. 

PMID- 24077256
TI  - Cadmium contamination of agricultural soils and crops resulting from sphalerite
      weathering.
AB  - The biogeochemistry and bioavailability of cadmium, released during sphalerite
      weathering in soils, were investigated under contrasting agricultural scenarios
      to assess health risks associated with sphalerite dust transport to productive
      soils from mining. Laboratory experiments (365 d) on temperate and sub-tropical
      soils amended with sphalerite (<63 MUm, 0.92 wt.% Cd) showed continuous, slow
      dissolution (0.6-1.2% y(-1)). Wheat grown in spiked temperate soil accumulated
      ~38% (29 MUmol kg(-1)) of the liberated Cd, exceeding food safety limits. In
      contrast, rice grown in flooded sub-tropical soil accumulated far less Cd (0.60
      MUmol kg(-1)) due to neutral soil pH and Cd bioavailability was possibly also
      controlled by secondary sulfide formation. The results demonstrate long-term
      release of Cd to soil porewaters during sphalerite weathering. Under oxic
      conditions, Cd may be sufficiently bioavailable to contaminate crops destined for
      human consumption; however flooded rice production limits the impact of
      sphalerite contamination. 

PMID- 24077257
TI  - PCDD/F and dioxin-like PCB bioaccumulation by Manila clam from polluted areas of
      Venice lagoon (Italy).
AB  - POP bioaccumulation pathways in the clam Tapes philippinarum were examined for
      two years from juveniles to adult size. Two polluted sites, one with sandy
      sediment, the other muddy were compared with a reference site characterized by
      low contamination levels. Juvenile clams coming from a hatchery were reared both
      on the sediment and in nets suspended at 30 cm from the bottom. POP changes in
      clam tissue were related to the concentrations recorded in sediments and in the
      particulate matter during the entire fattening period. Results provided
      interesting data on the relationships between environmental contamination and
      bioaccumulation. Contrary to studies on the decontamination times of the clams
      collected in polluted areas, this work investigates the preferential clam
      bioaccumulation pathways during growth under different environmental conditions.
      In general POP bioaccumulation resulted to be correlated to concentrations in SPM
      rather than in sediments and was higher in S-clams rather than in B-clams. 

PMID- 24077258
TI  - Dental application of novel finite element analysis software for three
      dimensional finite element modeling of a dentulous mandible from its computed
      tomography images.
AB  - This study focused on the application of novel finite-element analysis software
      for constructing a finite-element model from the computed tomography data of a
      human dentulous mandible. The finite-element model is necessary for evaluating
      the mechanical response of the alveolar part of the mandible, resulting from
      occlusal force applied to the teeth during biting. Commercially available patient
      specific general computed tomography-based finite-element analysis software was
      solely applied to the finite-element analysis for the extraction of computed
      tomography data. The mandibular bone with teeth was extracted from the original
      images. Both the enamel and the dentin were extracted after image processing, and
      the periodontal ligament was created from the segmented dentin. The constructed
      finite-element model was reasonably accurate using a total of 234,644 nodes and
      1,268,784 tetrahedral and 40,665 shell elements. The elastic moduli of the
      heterogeneous mandibular bone were determined from the bone density data of the
      computed tomography images. The results suggested that the software applied in
      this study is both useful and powerful for creating a more accurate three
      dimensional finite-element model of a dentulous mandible from the computed
      tomography data without the need for any other software. 

PMID- 24077259
TI  - Natural genotypes via genetic engineering.

PMID- 24077261
TI  - Turekian reflections.

PMID- 24077260
TI  - Hydrologic impacts of past shifts of Earth's thermal equator offer insight into
      those to be produced by fossil fuel CO2.
AB  - Major changes in global rainfall patterns accompanied a northward shift of
      Earth's thermal equator at the onset of an abrupt climate change 14.6 kya. This
      northward pull of Earth's wind and rain belts stemmed from disintegration of
      North Atlantic winter sea ice cover, which steepened the interhemispheric
      meridional temperature gradient. A southward migration of Earth's thermal equator
      may have accompanied the more recent Medieval Warm to Little Ice Age climate
      transition in the Northern Hemisphere. As fossil fuel CO2 warms the planet, the
      continents of the Northern Hemisphere are expected to warm faster than the
      Southern Hemisphere oceans. Therefore, we predict that a northward shift of
      Earth's thermal equator, initiated by an increased interhemispheric temperature
      contrast, may well produce hydrologic changes similar to those that occurred
      during past Northern Hemisphere warm periods. If so, the American West, the
      Middle East, and southern Amazonia will become drier, and monsoonal Asia,
      Venezuela, and equatorial Africa will become wetter. Additional paleoclimate data
      should be acquired and model simulations should be conducted to evaluate the
      reliability of this analog. 

PMID- 24077262
TI  - Bounded population sizes, fluctuating selection and the tempo and mode of
      coexistence.
AB  - Existing theory predicts competitors (species or genetic clones) cannot coexist
      in a fluctuating environment unless relative fitness is negatively frequency
      dependent (relative fitness declines as the frequency of a competitor increases).
      We develop simple theory to show coexistence does not require frequency-dependent
      selection, and we confirm this prediction by direct experiment. The conditions
      for coexistence in a fluctuating environment are precisely the same as those for
      coexistence in a spatially variable environment, conditions that arise naturally
      whenever population abundances are bounded. Simulations show the likelihood of
      coexistence increases with environmental uncertainty. The capacity of temporally
      variable environments to maintain biological diversity is far broader than
      generally envisaged. 

PMID- 24077263
TI  - Chemical reactivity and long-range transport potential of polycyclic aromatic
      hydrocarbons--a review.
AB  - Polycyclic aromatic hydrocarbons (PAHs) are of considerable concern due to their
      well-recognised toxicity and especially due to the carcinogenic hazard which they
      present. PAHs are semi-volatile and therefore partition between vapour and
      condensed phases in the atmosphere and both the vapour and particulate forms
      undergo chemical reactions. This article briefly reviews the current
      understanding of vapour-particle partitioning of PAHs and the PAH deposition
      processes, and in greater detail, their chemical reactions. PAHs are reactive
      towards a number of atmospheric oxidants, most notably the hydroxyl radical,
      ozone, the nitrate radical (NO3) and nitrogen dioxide. Rate coefficient data are
      reviewed for reactions of lower molecular weight PAH vapour with these species as
      well as for heterogeneous reactions of higher molecular weight compounds. Whereas
      the data for reactions of the 2-3-ring PAH vapour are quite extensive and
      generally consistent, such data are mostly lacking for the 4-ring PAHs and the
      heterogeneous rate data (5 and more rings), which are dependent on the substrate
      type and reaction conditions, are less comprehensive. The atmospheric reactions
      of PAH lead to the formation of oxy and nitro derivatives, reviewed here, too.
      Finally, the capacity of PAHs for long range transport and the results of
      numerical model studies are described. Research needs are identified. 

PMID- 24077264
TI  - Automated bone segmentation from large field of view 3D MR images of the hip
      joint.
AB  - Accurate bone segmentation in the hip joint region from magnetic resonance (MR)
      images can provide quantitative data for examining pathoanatomical conditions
      such as femoroacetabular impingement through to varying stages of osteoarthritis
      to monitor bone and associated cartilage morphometry. We evaluate two state-of
      the-art methods (multi-atlas and active shape model (ASM) approaches) on
      bilateral MR images for automatic 3D bone segmentation in the hip region
      (proximal femur and innominate bone). Bilateral MR images of the hip joints were
      acquired at 3T from 30 volunteers. Image sequences included water-excitation dual
      echo stead state (FOV 38.6 * 24.1 cm, matrix 576 * 360, thickness 0.61 mm) in all
      subjects and multi-echo data image combination (FOV 37.6 * 23.5 cm, matrix 576 *
      360, thickness 0.70 mm) for a subset of eight subjects. Following manual
      segmentation of femoral (head-neck, proximal-shaft) and innominate
      (ilium+ischium+pubis) bone, automated bone segmentation proceeded via two
      approaches: (1) multi-atlas segmentation incorporating non-rigid registration and
      (2) an advanced ASM-based scheme. Mean inter- and intra-rater reliability Dice's
      similarity coefficients (DSC) for manual segmentation of femoral and innominate
      bone were (0.970, 0.963) and (0.971, 0.965). Compared with manual data, mean DSC
      values for femoral and innominate bone volumes using automated multi-atlas and
      ASM-based methods were (0.950, 0.922) and (0.946, 0.917), respectively. Both
      approaches delivered accurate (high DSC values) segmentation results; notably,
      ASM data were generated in substantially less computational time (12 min versus
      10 h). Both automated algorithms provided accurate 3D bone volumetric
      descriptions for MR-based measures in the hip region. The highly computational
      efficient ASM-based approach is more likely suitable for future clinical
      applications such as extracting bone-cartilage interfaces for potential cartilage
      segmentation. 

PMID- 24077265
TI  - Mn(II) deposition on anodes and its effects on capacity fade in spinel lithium
      manganate-carbon systems.
AB  - Dissolution and migration of manganese from cathode lead to severe capacity
      fading of lithium manganate-carbon cells. Overcoming this major problem requires
      a better understanding of the mechanisms of manganese dissolution, migration and
      deposition. Here we apply a variety of advanced analytical methods to study
      lithium manganate cathodes that are cycled with different anodes. We show that
      the oxidation state of manganese deposited on the anodes is +2, which differs
      from the results reported earlier. Our results also indicate that a metathesis
      reaction between Mn(II) and some species on the solid-electrolyte interphase
      takes place during the deposition of Mn(II) on the anodes, rather than a
      reduction reaction that leads to the formation of metallic Mn, as speculated in
      earlier studies. The concentration of Mn deposited on the anode gradually
      increases with cycles; this trend is well correlated with the anodes rising
      impedance and capacity fading of the cell. 

PMID- 24077266
TI  - Germinoma in two brothers: case report.
AB  - We present a third reported case of intracranial germinomas occurring in two
      brothers. They underwent chemotherapy and radiotherapy after biopsy and are doing
      well for 10 years and 20 months, respectively. The pertinent literatures are
      reviewed, and the possible role of heredity in the pathogenesis of familial
      occurrence of germinomas is discussed. 

PMID- 24077267
TI  - Skull metastasis from intrahepatic cholangiocarcinoma: report of 3 cases and
      review of the literature.
AB  - Skull metastases occur in patients with various malignancies; however, those
      resulting from intrahepatic cholangiocarcinoma (ICC) have been rarely reported.
      In our hospital, 324 patients were diagnosed with metastatic brain or skull
      tumors from June 1969 to June 2011, but only 3 of them (0.9%) developed skull
      metastases from ICC. We report the case of 3 patients with skull metastases from
      ICC. A combination of computed tomography (CT), contrast-enhanced magnetic
      resonance imaging (MRI), 18F-fluorodeoxyglucose positron emission tomography (FDG
      PET), and methionine-PET were used for imaging. Sites of tumors were the lateral
      left orbit and right parietal bone in case 1, the left parietal bone, left
      temporal bone, and lateral left orbit in case 2, the right petrous bone, right
      occipital bone, and upper cervical vertebra in case 3. The metastases were
      confirmed to have originated from ICC by biopsy in two of the cases and diagnosed
      by MRI and FDG-PET in case 2. Radiosurgery and radiotherapy had positive effects
      on symptom improvement and cosmetic problems. 

PMID- 24077268
TI  - Convexity en plaque meningioma manifesting as subcutaneous mass: case report.
AB  - A 67-year-old woman sensed a slowly growing, painless hard mass in the left
      parietal region. Cranial computed tomography showed focal bony erosion and
      homogeneous sclerotic change at the affected site. Magnetic resonance (MR)
      imaging revealed an enhanced subcutaneous mass and irregularly thickened dura
      mater. Intraoperatively, the subcutaneous tumor was found to be strongly adhered
      to the temporalis muscle. The outer table was eroded adjacent to the subcutaneous
      tumor, whereas the bony structures of the inner table were intact. The dura mater
      underneath had irregular-shaped, yellowish convolutions both on the outer and
      inner surfaces. The patient underwent total tumor resection with sufficient
      normal margins. The histological diagnosis was World Health Organization (WHO)
      grade I meningioma, with finger-like outward extensions through the dura mater
      and overlying skull, and infiltration among into the temporalis muscle fibers.
      Meningiomas may form a subcutaneous mass without intracranial growth. 

PMID- 24077269
TI  - Long-term hearing outcome after retrosigmoid removal of vestibular schwannoma.
AB  - Although many investigators have reported the hearing function in the immediate
      postoperative period in patients with vestibular schwannoma (VS), little is known
      about the long-term outcomes of the postoperative hearing. The aim of this study
      was to analyze the long-term hearing outcomes at a mean follow-up of 5 years in
      patients with unilateral VS treated via the retrosigmoid approach. Twenty-four
      patients with immediate postoperative serviceable hearing who underwent repeated
      audiogram or phone interview were included in this study. During the mean follow
      up period (68.8 +/- 30.2 months, range 14-123 months), serviceable hearing was
      preserved in 20 out of the 24 patients (83%). Pure tone average (PTA) was
      reevaluated within 6 months in seven patients. In the two patients whose PTA
      deteriorated >= 5 dB in 6 months after surgery, their PTA worsened >= 15 dB
      compared to the immediate postoperative PTA. In the remaining five patients whose
      PTA deteriorated < 5 dB in 6 months after surgery, PTA was maintained within a 15
      dB deterioration at the final follow-up (p = 0.04, Fisher's exact test).
      According to Kaplan-Meier survival plots, the 5-year or 7-year preservation rate
      of serviceable hearing was 86.2% or 71.8%, respectively. Further study will be
      needed to clarify the mechanism underlying the long-term decline of serviceable
      hearing; however, the deterioration of PTA in the early postoperative period may
      help to predict the long-term outcomes of hearing. 

PMID- 24077270
TI  - Suprasellar hemangioblastoma mimicking a craniopharyngioma: result of extended
      endoscopic transsphenoidal approach--case report.
AB  - Hemangioblastoma in the suprasellar region is rare. We present a case of a
      suprasellar hemangioblastoma that underwent surgical resection using an extended
      endoscopic transsphenoidal approach. A 64-year-old female patient presented with
      headache and decreased visual acuity for the last four years, computed tomography
      (CT) and magnetic resonance imaging (MRI) revealed a 2.5 cm irregular lesion in
      the suprasellar region. Our preoperative presumptive diagnosis was
      craniopharyngioma. The patient underwent an extended endoscopic transsphenoidal
      approach, the mass was subtotally removed. An endoscopic endonasal repair was
      needed due to the cerebrospinal fluid (CSF) leak. However, 1 month later, the
      patient got disturbance of consciousness because of the hydrocephalus.
      Ventriculoperitoneal shunt was used to solve the problem. Pathological findings
      were compatible with hemangioblastoma. Suprasellar hemangioblastoma is very rare.
      Any highly vascular lesions located in the suprasellar region should alert the
      surgeon to the possibility of hemangioblastoma. Extended endoscopic
      transsphenoidal approach adopted by us should not be the first choice of the
      treatment procedure for this kind of large and vascular tumor. 

PMID- 24077271
TI  - Pituitary apoplexy caused by hemorrhage from pituitary metastatic melanoma: case
      report.
AB  - Melanoma metastases to the pituitary gland are extremely rare, with only a few
      reported cases. We report an unusual case of pituitary metastatic melanoma in
      which the patient presented with pituitary apoplexy. A 68-year-old man presented
      general fatigue and anorexia following sudden headache. Neurological examination
      disclosed bitemporal hemianopsia. Computed tomography (CT) scans revealed a
      suprasellar mass including intratumoral hematoma. Magnetic resonance (MR) images
      demonstrated a circumscribed mass lesion in the intra- and suprasellar regions,
      compressing the optic chiasm. Surgical exploration was performed through a
      transsphenoidal approach, and a mixture of tumor and necrotic tissue with old
      hematoma was obtained. The histological examination of the specimen revealed a
      partly necrotic, malignant tumor with focal melanotic pigmentation.
      Histopathologically, the diagnosis was consistent with pituitary apoplexy caused
      by hemorrhage from pituitary metastatic melanoma.

PMID- 24077272
TI  - Long-term follow-up of growth hormone-producing pituitary carcinoma with multiple
      spinal metastases following multiple surgeries: case report.
AB  - This report describes a rare case of a patient with growth hormone (GH)-secreting
      pituitary adenoma with malignant transformation resulting in multiple metastases
      to the dura mater of the cerebral convexity and high cervical spine. The patient
      was a 60-year-old man with a previous history of pituitary adenoma with
      suprasellar extension who had undergone transsphenoidal surgery, craniotomy for a
      convexity tumor, and suboccipital craniotomy for a cerebellar tumor. Thirteen
      years after the initial surgery, suboccipital craniotomy for a cervicomedullary
      junction tumor and cervicospinal surgery for a metastatic tumor was performed.
      Histologic findings of resected specimens demonstrated that the primary pituitary
      tumor was typical adenoma (similar to specimens from the initial surgery) but
      that the cerebellar and the dural tumor from the high cervical spine had a high
      incidence of mitotic figures, and cellular anaplasia with nuclear polymorphism
      and necrosis. In addition, the serum levels of GH were noted to have decreased
      with recurrence of the tumor. It was concluded that patients with pituitary
      adenoma, even when benign, must be carefully followed for signs of malignant
      transformation, and spinal or distant metastases. 

PMID- 24077273
TI  - Melanotic schwannoma of the cervical spine progressing with pulmonary metastasis:
      case report.
AB  - Melanotic schwannoma (MS) is an unusual variant of nerve sheath neoplasm. Only
      10% of these tumors will undergo malignant degeneration, with exceedingly rare
      reported metastasis. We present a 32-year-old woman with a 6-month history of
      cervical pain and left arm progressive weakness. Neurological examination showed
      a left upper limb radicular pain, with pyramidal syndrome at C5 level. The
      magnetic resonance imaging (MRI) study highlighted an intradural extramedullary
      heterogeneous mass along the spinal cord at the C4-C5 level, slightly
      hyperintense with T1 and hypointense with T2-weighted sequences, invading the
      left neural foramen. The patient underwent C3-C5 laminectomy with total resection
      of a black tumor. In the postoperative period, a patent deficit of shoulder
      abduction ensued related to the nervous section. Microscopically, compactly
      fascicles of spindle-shaped cells with pleomorphic and hypercromatic nuclei, dark
      brown intracellular pigments, as well as some mitotic figures were seen.
      Immunohistochemical stains for S-100, Human Melanoma Black-45 (HMB-45), and
      vimentin were positive, with Ki-67 Labelling Index (LI) of 15% compatible with
      MS. Six months after radiotherapy she presents local recurrence and lung
      metastatic dissemination of the MS. She underwent left pulmonary segmentectomy,
      followed by chemotherapy and radiosurgery. The patient developed a febrile
      neutropenia and worsening of general status, and died after 3 months due to
      respiratory complications. MS are rare tumors with potential for local recurrence
      and distal metastasis. Complete surgical resection remains as the treatment of
      choice, once the uncommon cases with malignant progression shows low response to
      chemo and radiotherapy. 

PMID- 24077274
TI  - Intramedullary and retroperitoneal melanocytic tumor associated with congenital
      blue nevus and nevus flammeus: an uncommon combination of neurocutaneous
      melanosis and phacomatosis pigmentovascularis--case report.
AB  - Neurocutaneous melanosis (NCM) is a rare condition characterized by central
      nervous system melanocytic tumors associated with congenital melanocytic nevi.
      Phacomatosis pigmentovascularis (PPV) is an association of vascular nevus with
      pigmentary nevus. Aberrant maturation of neural crest-derived cells is considered
      to be related to pathogenesis in both conditions. However, association of NCM and
      PPV has not been reported to the best of our knowledge. Melanocytoma, which
      usually involves the leptomeninges or spinal cord, is extremely rare in the
      retroperitoneum. We present here a case of a patient with NCM, PPV, and
      melanocytic tumors in the spinal cord and retroperitoneum, which were treated
      surgically. A 40-year-old woman had a 2-year history of dysesthesia and weakness
      in the left leg. History included congenital giant blue nevus-like lesion in the
      trunk, a port-wine stain in the sacral area, and Caesarean section performed 8
      years before, when diffuse pigmentation in the peritoneum was noted. Magnetic
      resonance (MR) imaging of the spine revealed an intramedullary tumor at T10 level
      with paramagnetic signal characteristics. The spinal cord tumor was totally
      removed, and the histological diagnosis was melanocytoma. Three months later, a
      left retroperitoneal mass with histological features of melanocytic tumor was
      removed. Neither tumors recurred and the patient stays ambulatory 4 years after
      the surgery. Multiple subtypes of melanocytic tumors with distinctive features of
      NCM and PPV can develop simultaneously, mimicking malignant melanoma. Gross total
      resection of each tumor, when indicated, is beneficial. 

PMID- 24077275
TI  - Slow progression of calcified cerebellar metastasis from ovarian cancer: a case
      report and review of the literature.
AB  - The report describes a rare case of a patient with a calcified cerebellar
      metastasis arising from a primary ovarian cancer. The patient was a 33-year-old
      woman with a long history of stage IIIc ovarian cancer who had undergone
      transabdominal hysterectomy and bilateral oophorectomy followed by chemotherapy
      with gemcitabine hydrochloride. Incidentally, computed tomography (CT) revealed a
      cerebellar tumor with calcification. The size of the tumor gradually increased,
      and lateral suboccipital craniotomy was performed for gross total removal of the
      tumor. The histological diagnosis was ovarian mucinous adenocarcinoma. The
      patient's postoperative course was uneventful, and she was discharged two days
      after surgery. Brain metastases from ovarian cancer are rare. In the review of
      metastatic brain tumors arising from a primary ovarian cancer in the Department
      of Obstetrics and Gynecology at our institution, this phenomenon was noted in
      only 10 cases (0.24%) of 4,158 patients with ovarian cancer seen at our center
      over a period of 8 years. Moreover, only three cases of calcified metastatic
      brain tumor have been reported previously. In conclusion, complete tumor
      resection may be an acceptable approach for patients with calcified metastatic
      tumors both for therapeutic considerations and to obtain tissue for confirmation
      of histopathological diagnosis. Metastatic brain tumors can be calcified, and
      should be considered within the differential diagnosis of calcified intracranial
      lesions to avoid any delay in diagnosis or treatment. 

PMID- 24077276
TI  - Characteristics of intraoperative abnormal hemodynamics during resection of an
      intra-fourth ventricular tumor located on the dorsal medulla oblongata.
AB  - Abnormal hemodynamics during extirpation of a para-medulla oblongata (MO) tumor
      is common and may be associated with direct vagal stimulation of the medullary
      circuit. However, resection of tumors on the dorsal MO may also induce
      hemodynamic instability without direct vagal stimulus. The objective of this
      study was to examine the characteristics of hemodynamic instability unrelated to
      vagal stimulus during dissection of an intra-fourth ventricular tumor with
      attachment to the dorsal MO. A retrospective analysis was performed in 13
      patients. Abnormal hemodynamics were defined as a > 20% change from the means of
      the intraoperative mean arterial pressure (MAP) and heart rate (HR).
      Relationships of intraoperative hemodynamics were evaluated with various
      parameters, including the volume of the MO. Six patients (46.2%) had
      intraoperative hypertension during separation of the tumor bulk from the dorsal
      MO. The maximum MAP and HR in these patients were significantly greater than
      those in patients with normal hemodynamics (116.0 +/- 18.0 mmHg versus 85.6 +/-
      6.5 mmHg; 124.3 +/- 22.8 bpm versus 90.5 +/- 14.7 bpm). All six cases with
      abnormal hemodynamics showed hemodynamic fluctuation during separation of the
      tumor bulk from the dorsal MO. The preoperative volume of the MO in these
      patients was 1.11 cc less than that in patients with normal hemodynamics, but the
      volume after tumor resection was similar in the two groups (5.23 cc and 5.12 cc).
      This suggests that the MO was compressed by the conglutinate tumor bulk, with
      resultant fluctuation of hemodynamics. Recognition of and preparation for this
      phenomenon are important for surgery on a tumor located on the dorsal MO. 

PMID- 24077277
TI  - An R132H mutation in isocitrate dehydrogenase 1 enhances p21 expression and
      inhibits phosphorylation of retinoblastoma protein in glioma cells.
AB  - Cytosolic isocitrate dehydrogenase 1 (IDH1) with an R132H mutation in brain
      tumors loses its enzymatic activity for catalyzing isocitrate to alpha
      ketoglutarate (alpha-KG) and acquires new activity whereby it converts alpha-KG
      to 2-hydroxyglutarate. The IDH1 mutation induces down-regulation of tricarboxylic
      acid cycle intermediates and up-regulation of lipid metabolism. Sterol regulatory
      element-binding proteins (SREBPs) regulate not only the synthesis of cholesterol
      and fatty acids but also acyclin-dependent kinase inhibitor p21 that halts the
      cell cycle at G1. Here we show that SREBPs were up-regulated in U87 human
      glioblastoma cells transfected with an IDH1(R132H)-expression plasmid. Small
      interfering ribonucleic acid (siRNA) for SREBP1 specifically decreased p21
      messenger RNA (mRNA) levels independent of the p53 pathway. In IDH1(R132H)
      expressing U87 cells, phosphorylation of Retinoblastoma (Rb) protein also
      decreased. We propose that metabolic changes induced by the IDH1 mutation enhance
      p21 expression via SREBP1 and inhibit phosphorylation of Rb, which slows
      progression of the cell cycle and may be associated with non-aggressive features
      of gliomas with an IDH1 mutation. 

PMID- 24077278
TI  - Intramedullary medullocervical ependymoma--surgical treatment, functional
      recovery, and long-term outcome.
AB  - To evaluate the long-term outcome and functional recovery of intramedullary
      medullocervical ependymoma (IME), the clinical charts of 38 surgically treated
      consecutive cases of IME were reviewed. Follow-up was obtained prospectively. The
      mean age of the patients (19 male and 19 female) was 35.3 years (range: 11-60
      years). Complete resection was achieved in 33 (86.8%) patients. Fourteen patients
      worsened postoperatively; five and seven of these improved to their baseline
      levels within 1 and 3 months, respectively. By 1 year postoperatively, 17
      patients returned to work. After a mean follow-up duration of 81.5 months, 31
      patients improved or stabilized, and 3 had recurrence. The means of the modified
      McCormick grade (mMG) scores before the operation, at discharge, 1 year after the
      operation, and at the most recent evaluation were 1.76, 2.13, 1.82, and 1.84,
      respectively. A favorable long-term outcome of the mMG was associated with a good
      preoperative status (mMG I) (odds ratio [OR] = 9.956, p = 0.008) and well-defined
      tumor boundary (OR = 7.829, p = 0.035). Improvements in the postoperative walking
      dysfunction and paresthesia over time were associated with the absence of
      preoperative walking dysfunction (p = 0.047) and paresthesia (p = 0.028),
      respectively. The 12-year progression/recurrence-free survival and overall
      survival rates were 92.0% and 93.7%, respectively. The study suggests that the
      goal of surgery is to stabilize the preoperative neurological function and that a
      favorable outcome may be achieved in patients with good preoperative statuses and
      well-defined tumor boundaries. Surgery should be performed as soon as possible
      after the diagnoses and before the neurological functions deteriorate. 

PMID- 24077279
TI  - Electrocorticographic-histopathologic correlations implying epileptogenicity of
      dysembryoplastic neuroepithelial tumor.
AB  - Based on intracranial-video electroencephalography (EEG), histopathological
      features, and postoperative seizure outcome, we elucidated the epileptogenicity
      in patients with dysembryoplastic neuroepithelial tumor (DNT). Five patients (P1
      P5) pathologically diagnosed with DNT underwent intracranial-video EEG to
      identify the ictal onset zone and irritative zone. We evaluated the correlations
      of ictal onset zone and irritative zone with the magnetic resonance imaging
      visible lesion (MRI-lesion) and their histopathological features. Intracranial
      video EEG located the ictal onset zone adjacent to the MRI-lesion margin in four
      patients with complex/simple forms of DNT subcategory, and on the MRI-lesion in
      P3 with a nonspecific DNT form. The irritative zone extended to surrounding
      regions of the ictal onset zone in all patients. Histopathologically, MRI-lesions
      were characterized by specific glioneuronal elements, whereas the ictal onset
      zone and irritative zone were represented with dysplastic cortex accompanying
      oligodendroglia-like cells in four (P1, P2, P4, and P5) of five patients.
      Cortical dysplasia was identified with typical histopathologic features in the
      irritative zone remote from the MRI-lesion in P5. P3, with a nonspecific form,
      indicated prominent component of dysplastic cortex with oligodendroglia-like
      cells scattered in the MRI-lesion. Lesionectomy of MRI-lesion with additional
      cortical resections (including the ictal onset zone and irritative zone) yielded
      postoperative seizure freedom (Engel Class I) in P3, P4, and P5, while P1 and P2
      (with only lesionectomy) experienced postoperative residual seizure (Class II and
      III in each patient). Our results suggest the intrinsic epileptogenicity of DNT.
      The topographical correlation indicated that the dysplastic cortex accompanying
      oligodendroglia-like cells was more epileptogenic than the specific glioneuronal
      elements itself. Meticulous intracranial-video EEG analysis delineating the MRI
      nonvisible ictal onset zone and the irritative zone may yield better seizure
      outcome. 

PMID- 24077280
TI  - Cell type-dependent pathogenic functions of overexpressed human cathepsin B in
      murine breast cancer progression.
AB  - The cysteine protease cathepsin B (CTSB) is frequently overexpressed in human
      breast cancer and correlated with a poor prognosis. Genetic deficiency or
      pharmacological inhibition of CTSB attenuates tumor growth, invasion and
      metastasis in mouse models of human cancers. CTSB is expressed in both cancer
      cells and cells of the tumor stroma, in particular in tumor-associated
      macrophages (TAM). In order to evaluate the impact of tumor- or stromal cell
      derived CTSB on Polyoma Middle T (PyMT)-induced breast cancer progression, we
      used in vivo and in vitro approaches to induce human CTSB overexpression in PyMT
      cancer cells or stromal cells alone or in combination. Orthotopic transplantation
      experiments revealed that CTSB overexpression in cancer cells rather than in the
      stroma affects PyMT tumor progression. In 3D cultures, primary PyMT tumor cells
      showed higher extracellular matrix proteolysis and enhanced collective cell
      invasion when CTSB was overexpressed and proteolytically active. Coculture of
      PyMT cells with bone marrow-derived macrophages induced a TAM-like macrophage
      phenotype in vitro, and the presence of such M2-polarized macrophages in 3D
      cultures enhanced sprouting of tumor spheroids. We employed a doxycycline (DOX)
      inducible CTSB expression system to selectively overexpress human CTSB either in
      cancer cells or in macrophages in 3D cocultures. Tumor spheroid invasiveness was
      only enhanced when CTSB was overexpressed in cancer cells, whereas CTSB
      expression in macrophages alone did not further promote invasiveness of tumor
      spheroids. We conclude that CTSB overexpression in the PyMT mouse model promotes
      tumor progression not by a stromal effect, but by a direct, cancer cell-inherent
      mode of action: CTSB overexpression renders the PyMT cancers more invasive by
      increasing proteolytic extracellular matrix protein degradation fostering
      collective cell invasion into adjacent tissue. 

PMID- 24077281
TI  - FOXO3a loss is a frequent early event in high-grade pelvic serous carcinogenesis.
AB  - Serous ovarian carcinoma is the most lethal gynecological malignancy in Western
      countries. The molecular events that underlie the development of the disease have
      been elusive for many years. The recent identification of the fallopian tube
      secretory epithelial cells (FTSECs) as the cell-of-origin for most cases of this
      disease has led to studies aimed at elucidating new candidate therapeutic
      pathways through profiling of normal FTSECs and serous carcinomas. Here we
      describe the results of transcriptional profiles that identify the loss of the
      tumor suppressive transcription factor FOXO3a in a vast majority of high-grade
      serous ovarian carcinomas. We show that FOXO3a loss is a hallmark of the earliest
      stages of serous carcinogenesis and occurs both at the DNA, RNA and protein
      levels. We describe several mechanisms responsible for FOXO3a inactivity,
      including chromosomal deletion (chromosome 6q21), upregulation of miRNA-182 and
      destabilization by activated PI3K and MEK. The identification of pathways
      involved in the pathogenesis of ovarian cancer can advance the management of this
      disease from being dependant on surgery and cytotoxic chemotherapy alone to the
      era of targeted therapy. Our data strongly suggest FOXO3a as a possible target
      for clinical intervention. 

PMID- 24077282
TI  - Pivotal role of augmented alphaB-crystallin in tumor development induced by
      deficient TSC1/2 complex.
AB  - Tuberous sclerosis complex 1 (TSC1) and TSC2 are suppressors of mechanistic
      target of rapamycin (mTOR). mTOR is the major component of two protein complexes:
      mTOR complex 1 (mTORC1) and mTORC2. Inactive mutation of either TSC1 or TSC2
      unleashes mTOR signaling and consequently causes TSC, a benign tumor syndrome
      affecting multiple organs. We report here that expression of alphaB-crystallin
      was upregulated in Tsc1-/- or Tsc2-/- mouse embryonic fibroblasts, Eker rat
      uterine leiomyoma-derived Tsc2-deficient ELT3 cells, mutant Tsc2-associated mouse
      kidney tumors, and human lung lymphangioleiomyomatosis nodules. alphaB-crystallin
      was transcriptionally activated by mTOR complex 2 (mTORC2): nuclear factor-kappa
      B (NFkappaB) signaling cascade. The augmented alphaB-crystallin was critical for
      the migration, invasion and apoptotic resistance of Tsc2-defective cells.
      Disruption of alphaB-crystallin suppressed Tsc2-null cell proliferation and
      tumorigenesis. Therefore, enhanced alphaB-crystallin has an essential role in
      TSC1/2 complex deficiency-mediated tumorigenesis, and inhibition of alphaB
      crystallin may complement the current therapy for TSC. 

PMID- 24077284
TI  - Signaling events mediated by alpha3beta1 integrin are essential for mammary
      tumorigenesis.
AB  - The constitutive activation of beta-catenin signaling in the mammary basal
      epithelial cell layer in transgenic K5DeltaNbetacat mice leads to basal-type
      tumor development. Integrins of the beta1 family and integrin-mediated signaling
      events have an important role in breast tumor growth and progression. We show
      here that the deletion of alpha3beta1 integrin, a major laminin receptor, from
      the basal layer of the mammary epithelium of K5DeltaNbetacat mice completely
      prevented the tumorigenesis induced by beta-catenin signaling. Moreover, the
      depletion of alpha3beta1 integrin from a spontaneously transformed mouse mammary
      basal epithelial cell line (MEC) prevented the cells from forming colonies in
      soft agar and greatly reduced tumor development in orthotopic grafts. Inhibition
      of the integrin signaling intermediates Rac1 or PAK1 (P21-activated Kinase 1) in
      MEC affected tumor cell growth in soft agar, whereas the expression of activated
      forms of these effectors in alpha3-depleted cells rescued the capacity of these
      cells to grow in non-adherent conditions. Similarly, the tumorigenic potential of
      alpha3-depleted cells was restored by the expression of activated PAK1, as
      assessed by orthotopic transplantation assay. In three-dimensional Matrigel
      culture, MEC survival and proliferation were affected by the depletion of
      alpha3beta1 integrin, which also significantly decreased the activation of focal
      adhesion kinase (FAK), mitogen-activated protein kinase (MAPK) and c-Jun NH2
      terminal kinase (JNK). Our data suggest that the activation of signaling cascades
      downstream from alpha3beta1 and involving the Rac1/PAK1 pathway, MAPK and JNK,
      promotes prosurvival and proproliferative signals required for the malignant
      growth of basal mammary epithelial cells, providing further insight into the
      molecular mechanisms underlying breast cancer initiation and progression. 

PMID- 24077283
TI  - Invading one step at a time: the role of invadopodia in tumor metastasis.
AB  - The ability to degrade extracellular matrix is critical for tumor cells to invade
      and metastasize. Recent studies show that tumor cells use specialized actin-based
      membrane protrusions termed invadopodia to perform matrix degradation.
      Invadopodia provide an elegant way for tumor cells to precisely couple focal
      matrix degradation with directional movement. Here we discuss several key
      components and regulators of invadopodia that have been uniquely implicated in
      tumor invasion and metastasis. Furthermore, we discuss existing and new
      therapeutic opportunities to target invadopodia for anti-metastasis treatment. 

PMID- 24077285
TI  - An EGFR wild type-EGFRvIII-HB-EGF feed-forward loop regulates the activation of
      EGFRvIII.
AB  - EGFRvIII is a key oncogene in glioblastoma (GBM). EGFRvIII results from an in
      frame deletion in the extracellular domain of EGFR, does not bind ligand and is
      thought to be constitutively active. Although EGFRvIII dimerization is known to
      activate EGFRvIII, the factors that drive EGFRvIII dimerization and activation
      are not well understood. Here we present a new model of EGFRvIII activation and
      propose that oncogenic activation of EGFRvIII in glioma cells is driven by co
      expressed activated EGFR wild type (EGFRwt). Increasing EGFRwt leads to a
      striking increase in EGFRvIII tyrosine phosphorylation and activation while
      silencing EGFRwt inhibits EGFRvIII activation. Both the dimerization arm and the
      kinase activity of EGFRwt are required for EGFRvIII activation. EGFRwt activates
      EGFRvIII by facilitating EGFRvIII dimerization. We have previously identified HB
      EGF, a ligand for EGFRwt, as a gene induced specifically by EGFRvIII. In this
      study, we show that HB-EGF is induced by EGFRvIII only when EGFRwt is present.
      Remarkably, altering HB-EGF recapitulates the effect of EGFRwt on EGFRvIII
      activation. Thus, increasing HB-EGF leads to a striking increase in EGFRvIII
      tyrosine phosphorylation while silencing HB-EGF attenuates EGFRvIII
      phosphorylation, suggesting that an EGFRvIII-HB-EGF-EGFRwt feed-forward loop
      regulates EGFRvIII activation. Silencing EGFRwt or HB-EGF leads to a striking
      inhibition of EGFRvIII-induced tumorigenicity, while increasing EGFRwt or HB-EGF
      levels resulted in accelerated EGFRvIII-mediated oncogenicity in an orthotopic
      mouse model. Furthermore, we demonstrate the existence of this loop in human GBM.
      Thus, our data demonstrate that oncogenic activation of EGFRvIII in GBM is likely
      maintained by a continuous EGFRwt-EGFRvIII-HB-EGF loop, potentially an attractive
      target for therapeutic intervention. 

PMID- 24077286
TI  - Tumor resident mesenchymal stromal cells endow naive stromal cells with tumor
      promoting properties.
AB  - Bone marrow mesenchymal stem/stromal cells (BM-MSCs) can infiltrate into tumors
      and subsequently evolve into tumor resident MSCs in tumor microenvironment. In
      this study, using a mouse lymphoma model, we showed that the lymphoma resident
      MSCs (L-MSCs) are able to confer tumor-promoting property to the naive cocultured
      BM-MSCs. Examination of cytokines and chemokines showed that post exposure to L
      MSCs, BM-MSCs acquired an expression profile that is similar to that in L-MSCs.
      In vivo, BM-MSCs educated by L-MSCs (BM-L-MSCs) possess a greatly enhanced
      ability in promoting lymphoma growth. Consistent with an elevated CCL-2
      expression in BM-L-MSCs, the tumor-promoting effect of BM-L-MSCs largely depends
      on CCR2-mediated macrophage recruitment to tumor sites. We further showed that
      the transmission of tumor-promoting effect is partially mediated by soluble
      factors. Our findings thus revealed a novel reinforcing mechanism in the
      maintenance of tumor microenvironment.

PMID- 24077287
TI  - Epithelial splicing regulatory protein 1 is a favorable prognostic factor in
      pancreatic cancer that attenuates pancreatic metastases.
AB  - Epithelial splicing regulatory protein 1 (ESRP1) binds the FGFR-2 auxiliary cis
      element ISE/ISS-3, located in the intron between exon IIIb and IIIc, and
      primarily promotes FGFR-2 IIIb expression. Here we assessed the role of ESRP1 in
      pancreatic ductal adenocarcinoma (PDAC). Immunohistochemical analysis was
      performed using anti-ESRP1, FGFR-2 IIIb and FGFR-2 IIIc antibodies in 123 PDAC
      cases. ESRP1 expression vector and small interference RNA (siRNA) targeting ESRP1
      were transfected into human PDAC cells, and cell growth, migration and invasion
      were analyzed. In vivo heterotopic and orthotopic implantations using ESRP1
      overexpression clones were performed and effects on pancreatic tumor volumes and
      hepatic and pulmonary metastases determined. ESRP1 immunoreactivity was strong in
      the nuclei of cancer cells in well-to-moderately differentiated PDACs but weak in
      poorly differentiated cancers. Well-to-moderately differentiated cancers also
      exhibited high FGFR-2 IIIb and low FGFR-2 IIIc expression, whereas this ratio was
      reversed in the poorly differentiated cancers. Increased ESRP1 expression was
      associated with longer survival in comparison with low ESRP1 expression, and PANC
      1 cells engineered to express ESRP1 exhibited increased FGFR-2 IIIb expression
      and decreased migration and invasion in vitro, whereas ESRP1 siRNA-transfected
      KLM-1 cells exhibited increased FGFR-2 IIIc expression and increased cell growth,
      migration and invasion. In vivo, ESRP1-overexpressing clones formed significantly
      fewer liver metastases as compared with control clones. ESRP1 regulates the
      expression pattern of FGFR-2 isoforms, attenuates cell growth, migration,
      invasion and metastasis, and is a favorable prognostic factor in PDAC. Therefore,
      devising mechanisms to upregulate ESRP1 may exert a beneficial therapeutic effect
      in PDAC. 

PMID- 24077288
TI  - Antibody-directed coupling of endoglin and MMP-14 is a key mechanism for endoglin
      shedding and deregulation of TGF-beta signaling.
AB  - Endoglin is a transforming growth factor beta (TGF-beta) coreceptor that serves
      as a prognostic, diagnostic and therapeutic vascular target in human cancer. A
      number of endoglin ectodomain-targeting antibodies (Abs) can effectively suppress
      both normal and tumor-associated angiogenesis, but their molecular actions remain
      poorly characterized. Here we define a key mechanism for TRACON105 (TRC105), a
      humanized monoclonal Ab in clinical trials for treatment of advanced or
      metastatic tumors. TRC105, along with several other endoglin Abs tested, enhance
      endoglin shedding through direct coupling of endoglin and the membrane-type 1
      matrix metalloproteinase (MMP)-14 at the cell surface to release the
      antiangiogenic factor, soluble endoglin (sEng). In addition to this coupling
      process, endoglin shedding is further amplified by increased MMP-14 expression
      that requires TRC105 concentration-dependent c-Jun N-terminal kinase (JNK)
      activation. There were also notable counterbalancing effects on canonical Smad
      signaling in which TRC105 abrogated both the steady-state and TGF-beta-induced
      Smad1/5/8 activation while augmenting Smad2/3 activation. Interestingly, TRC105
      induced sEng and aberrant Smad signaling resulted in an excessive migratory
      response through enhanced stress fiber formation and disruption of endothelial
      cell-cell junctions. Collectively, our study defines endoglin shedding and
      deregulated TGF-beta signaling during migration as major mechanisms by which
      TRC105 inhibits angiogenesis.

PMID- 24077289
TI  - Estrogen receptor beta upregulates FOXO3a and causes induction of apoptosis
      through PUMA in prostate cancer.
AB  - Estrogen receptor beta (ERbeta) is emerging as a critical factor in understanding
      prostate cancer biology. Although reduced in prostate cancer above Gleason grade
      3, ERbeta is a potential drug target at the initial stage of the disease. In
      human prostate cancer cells, we found that ERbeta causes apoptosis by increasing
      the expression of pro-apoptotic factor p53-upregulated modulator of apoptosis
      (PUMA), independent of p53, but dependent on the forkhead transcription factor
      class-O family member, FOXO3a. FOXO3a has previously been shown to induce PUMA
      after growth factor withdrawal and inhibition of the Akt pathway. Surprisingly,
      the phosphorylation of FOXO3a remained unchanged, while the mRNA and total
      protein levels of FOXO3a were increased in response to ERbeta expression or
      treatment of PC3, 22Rv1 and LNCaP cells with the ERbeta-specific ligands 3beta
      Adiol (5alpha-androstane-3beta,17beta-diol), DPN (diarylpropionitrile) or 8beta
      VE2 (8-vinylestra-1,3,5 (10)-triene-3,17beta-diol). Knockdown of FOXO3a or ERbeta
      expression abolished the increase of PUMA in response to 3beta-Adiol in LNCaP and
      PC3 cells, suggesting that FOXO3a mediates the apoptotic effect of 3beta-Adiol
      activated ERbeta. Moreover, the ventral prostate of ERbeta-/- mice had decreased
      expression of FOXO3a and PUMA compared with the ERbeta+/+ mice, indicating a
      relationship between ERbeta and FOXO3a expression. The regulation of FOXO3a by
      ERbeta in normal basal epithelial cells indicates a function of ERbeta in cell
      differentiation and maintenance of cells in a quiescent state. In addition, the
      expression of ERbeta, FOXO3a and PUMA is comparable and higher in benign
      prostatic hyperplasia than in prostate cancer Gleason grade 4 or higher, where
      there is substantial loss of ERbeta, FOXO3a and PUMA. We conclude that ERbeta
      induces apoptosis of prostate cancer cells by increasing transcription of FOXO3a,
      leading to an increase of PUMA and subsequent triggering of apoptosis via the
      intrinsic pathway involving caspase-9. Furthermore, we conclude that ligands
      specifically activating ERbeta could be useful pharmaceuticals in the treatment
      of prostate cancer. 

PMID- 24077290
TI  - A small compound targeting TACC3 revealed its different spatiotemporal
      contributions for spindle assembly in cancer cells.
AB  - The mitotic spindle is assembled by the coordinated action of centrosomes and
      kinetochore microtubules. An evolutionally conserved protein family, transforming
      acidic coiled-coil (TACC), has been shown to be involved in this process. In
      humans, TACC3 is aberrantly expressed in a variety of human cancers, but its
      biological significance remains to be elucidated. Here, using a novel compound
      targeting TACC3, spindlactone (SPL), we show that the perturbation of TACC3
      selectively inhibited the nucleation of centrosome microtubules in ovarian cancer
      cells. In contrast to centrosome microtubules, the kinetochore microtubules were
      robustly assembled, forming ectopic spindle poles that resulted in multipolar
      spindles. Interestingly, the extensive inhibition of TACC3 partially suppressed
      the nucleation of kinetochore microtubules. These dose-dependent effects of SPL
      were consistent with the results observed by the depletion of TACC3 and its
      binding partner, colonic and hepatic tumor overexpressed gene protein (TOGp).
      Although these proteins both have roles in the assembly of centrosome and
      kinetochore microtubules, their contributions were spatiotemporally different.
      Notably, SPL did not affect spindle assembly in normal cells. Furthermore, the
      oral administration of SPL significantly suppressed tumor growth in vivo. The
      unique mechanism of action of SPL not only enables it to be used as a tool to
      dissect the molecular basis of spindle assembly but also to provide a rationale
      for the use of TACC3 as a molecular target for cancer treatment. This rationale
      offers an opportunity to develop new strategies for cancer chemotherapy that
      overcome the limitations of microtubule toxins and expand their scope and
      clinical efficacy. 

PMID- 24077291
TI  - Inhibition of monocarboxylate transporter-4 depletes stem-like glioblastoma cells
      and inhibits HIF transcriptional response in a lactate-independent manner.
AB  - Hypoxic regions are frequent in glioblastoma (GBM), the most common type of
      malignant adult brain tumor, and increased levels of tumor hypoxia have been
      associated with worse clinical outcomes. To unmask genes important in hypoxia, we
      treated GBM neurospheres in hypoxia and identified monocarboxylate transporter-4
      (MCT4) as one of the most upregulated genes. To investigate the clinical
      importance of MCT4 in GBM, we examined clinical outcomes and found that MCT4
      overexpression is associated with shorter patient survival. Consistent with this,
      MCT4 upregulation correlated with the aggressive mesenchymal subset of GBM, and
      MCT4 downregulation correlated with the less aggressive G-CIMP (Glioma CpG
      Methylator Phenotype) subset of GBM. Immunohistochemical analysis of tissue
      microarrays confirmed that MCT4 protein levels were increased in high-grade as
      compared with lower-grade astrocytomas, further suggesting that MCT4 is a
      clinically relevant target. To test the requirement for MCT4 in vitro, we
      transduced neurospheres with lentiviruses encoding short-hairpin RNAs (shRNAs)
      against MCT4, resulting in growth inhibition of 50-80% under hypoxia in two
      lines. MCT4 knockdown was associated with a decreased percentage of cells
      expressing the stem-cell marker CD133 and increased apoptotic fraction. We also
      found that flow-sorted CD133-positive cells had almost sixfold higher MCT4 levels
      than CD133-negative cells, suggesting that the stem-like population might have a
      greater requirement for MCT4. Most importantly, MCT4 silencing also slowed GBM
      intracranial xenograft growth in vivo. Interestingly, whereas MCT4 is a well
      characterized lactate exporter, we found that both intracellular and
      extracellular lactate levels did not change following MCT4 silencing, suggesting
      a novel lactate export-independent mechanism for growth inhibition in GBMs. To
      identify this potential mechanism, we performed microarray analysis on control
      and shMCT4-expressing neurospheres and found a dramatic reduction in the
      expression of multiple Hypoxia-Inducible Factor (HIF)-regulated genes following
      MCT4 knockdown. The overall reduction in HIF transcriptional response was further
      validated using a hypoxia response element (HRE)-dependent green-fluorescent
      protein (GFP) reporter line. 

PMID- 24077292
TI  - Early induction of Fe-SOD gene expression is involved in tolerance to Mn toxicity
      in perennial ryegrass.
AB  - Manganese (Mn) toxicity limits plant growth in acid soils. Although Mn toxicity
      induces oxidative stress, the role of superoxide dismutase (SOD, EC.1.15.1.1)
      isoforms in conferring Mn tolerance remains unclear. Seedlings of ryegrass
      cultivars Nui (Mn-sensitive) and Kingston (Mn-tolerant) were hydroponically grown
      at 2.4 (optimal) or 750 MUM Mn (toxic) concentration, and harvested from 2 to 48
      h. Kingston showed higher shoot Mn than Nui at 2.4 MUM Mn. At toxic supply, shoot
      Mn concentration steadily increased in both cultivars, with Kingston having the
      highest accumulation at 48 h. An early (2 h) increase in lipid peroxidation under
      Mn excess occurred, but it returned (after 6 h) to the basal level in Kingston
      only. Kingston exhibited higher SOD activity than Nui, and that difference
      increased due to toxic Mn. In general, Mn-induced gene expression of Mn- and
      Cu/Zn-SOD isoforms was higher in Nui than Kingston. Nevertheless, under Mn
      excess, we found a greater Fe-SOD up-regulation (up to 5-fold) in Kingston
      compared to Nui. Thus, Fe-SOD induction in Kingston might explain, at least
      partly, its high tolerance to Mn toxicity. This is the first evidence that Mn
      toxicity causes differential gene expression of SOD isoforms in ryegrass
      cultivars in the short-term. 

PMID- 24077294
TI  - Molecular endocrinology articles in the spotlight for October 2013.

PMID- 24077296
TI  - New vaccinia virus promoter as a potential candidate for future vaccines.
AB  - Here we describe the design and strength of a new synthetic late-early optimized
      (LEO) vaccinia virus (VACV) promoter used as a transcriptional regulator of GFP
      expression during modified vaccinia Ankara infection. In contrast to the
      described synthetic VACV promoter (pS), LEO induced significantly higher levels
      of GFP expression in vitro within the first hour after infection, which
      correlated with an enhancement in the GFP-specific CD8 T-cell response detected
      in vivo, demonstrating its potential use in future vaccines. 

PMID- 24077297
TI  - Whole-genome sequences of two turkey adenovirus types reveal the existence of two
      unknown lineages that merit the establishment of novel species within the genus
      Aviadenovirus.
AB  - There are eight species established for aviadenoviruses: Fowl adenovirus A-E,
      Goose adenovirus A, Falcon adenovirus A and Turkey adenovirus B. The aim of this
      study was to sequence and analyse the complete genomes of turkey adenovirus 4
      (TAdV-4) and TAdV-5 (strain 1277BT) in addition to almost two-thirds of the
      genome of another TAdV-5 strain (strain D1648). By applying next-generation
      sequencing, the full genomes were found to be 42 940 and 43 686 bp and the G+C
      content was 48.5 and 51.6 mol% for TAdV-4 and TAdV-5, respectively. One fiber
      gene was identified in TAdV-4, whereas two fiber genes were found in TAdV-5. The
      genome organization of TAdV-4 resembled that of fowl adenovirus 5 (FAdV-5), but
      it had ORF1C near the left end of the genome. TAdV-4 also had five 123 bp tandem
      repeats followed by five 33 bp tandem repeats, but they occurred before and not
      after ORF8, as in several fowl adenoviruses. The genome organization of TAdV-5
      was almost the same as that of FAdV-1 but with a possible difference in the
      splicing pattern of ORF11 and ORF26. Phylogenetic analyses and G+C content showed
      differences that seem to merit the establishment of two new species within the
      genus Aviadenovirus: Turkey adenovirus C (for TAdV-4) and Turkey adenovirus D
      (for TAdV-5). Our analyses suggest a common evolutionary origin of TAdV-5 and
      FAdV-1. 

PMID- 24077299
TI  - Implementation of non-equilibrium vertex corrections in KKR: transport through
      disordered layers.
AB  - The theoretical description of modern nanoelectronic devices requires a quantum
      mechanical treatment and often involves disorder, e.g. from alloys. Therefore,
      the ab initio theory of transport using non-equilibrium Green's functions is
      extended to the case of disorder described by the coherent potential
      approximation. This requires the calculation of non-equilibrium vertex
      corrections. We implement the vertex corrections in a Korringa-Kohn-Rostoker
      multiple scattering scheme. In order to verify our implementation and to
      demonstrate the accuracy and applicability we investigate a system of an iron
      cobalt alloy layer embedded in copper. The results obtained with the coherent
      potential approximation are compared to supercell calculations. It turns out that
      vertex corrections play an important role for this system.

PMID- 24077298
TI  - Evolution of DS-1-like human G2P[4] rotaviruses assessed by complete genome
      analyses.
AB  - Group A rotaviruses (RVAs) are a leading cause of viral gastroenteritis in
      children, with G2P[4] RVA being one of the most common human strains worldwide.
      The complete genome sequences of nine G2P[4] RVA strains, selected from a 26-year
      archival collection (1985-2011) established in Palermo, Italy, were determined. A
      strain associated with a peak of G2P[4] RVA activity in 1996 resembled a
      reassortant strain identified in Kenya in 1982 and differed completely in genomic
      make up from more recent strains that circulated during 2004-2011. Conversely,
      the 2004-2011 G2P[4] RVAs were genetically more similar to contemporary RVA
      strains circulating globally. Recent G2P[4] strains possessed either single or
      multiple genome segments (VP1, VP3 and/or NSP4) likely derived from ruminant
      viruses through intra-genotype reassortment. Amino acid substitutions were
      selected and maintained over time in the VP7 and VP8* antigenic proteins,
      allowing the circulation of two contemporary G2P[4] variants to be distinguished.
      Altogether, these findings suggest that major changes in the genomic composition
      of recent G2P[4] RVAs occurred in the early 2000s, leading to the appearance of a
      novel variant of the DS-1-like genotype constellation. Whether the modifications
      observed in the neutralizing antigens and in the genome composition of modern
      G2P[4] RVAs may affect the long-term effectiveness of the vaccination programmes
      remains to be explored. 

PMID- 24077300
TI  - Comparing two epidemiologic surveillance methods to assess underestimation of
      human stampedes in India.
AB  - BACKGROUND: Two separate but complementary epidemiologic surveillance methods for
      human stampedes have emerged since the publication of the topic in 2009. The
      objective of this study is to estimate the degree of underreporting in India.
      METHOD: The Ngai Search Method was compared to the Roy Search Method for human
      stampede events occurring in India between 2001 and 2010. RESULTS: A total of 40
      stampedes were identified by both search methods. Using the Ngai method, 34 human
      stampedes were identified. Using a previously defined stampede scale: 2 events
      were class I, 21 events were class II, 8 events were class III, and 3 events were
      class IV. The median deaths were 5.5 per event and median injuries were 13.5 per
      event. Using the Roy method, 27 events were identified, including 9 events that
      were not identified by the Ngai method. After excluding events based on exclusion
      criteria, six additional events identified by the Roy's method had a median of 4
      deaths and 30 injuries. In multivariate analysis using the Ngai method, religious
      (6.52, 95%CI 1.73-24.66, p=0.006) and political (277.09, 95%CI 5.12-15,001.96,
      p=0.006) events had higher relative number of deaths. CONCLUSION: Many causes
      accounting for the global increase in human stampede events can only be
      elucidated through systematic epidemiological investigation. Focusing on a
      country with a high recurrence of human stampedes, we compare two independent
      methods of data abstraction in an effort to improve the existing database and to
      identify pertinent risk factors. We concluded that our previous publication
      underestimated stampede events in India by approximately 18% and an international
      standardized database to systematically record occurrence of human stampedes is
      needed to facilitate understanding of the epidemiology of human stampedes.

PMID- 24077301
TI  - Noncoding RNAs of the Ultrabithorax domain of the Drosophila bithorax complex.
AB  - RNA transcripts without obvious coding potential are widespread in many
      creatures, including the fruit fly, Drosophila melanogaster. Several noncoding
      RNAs have been identified within the Drosophila bithorax complex. These first
      appear in blastoderm stage embryos, and their expression patterns indicate that
      they are transcribed only from active domains of the bithorax complex. It has
      been suggested that these noncoding RNAs have a role in establishing active
      domains, perhaps by setting the state of Polycomb Response Elements A
      comprehensive survey across the proximal half of the bithorax complex has now
      revealed nine distinct noncoding RNA transcripts, including four within the
      Ultrabithorax transcription unit. At the blastoderm stage, the noncoding
      transcripts collectively span ~75% of the 135 kb surveyed. Recombination-mediated
      cassette exchange was used to invert the promoter of one of the noncoding RNAs, a
      23-kb transcript from the bxd domain of the bithorax complex. The resulting
      animals fail to make the normal bxd noncoding RNA and show no transcription
      across the bxd Polycomb Response Element in early embryos. The mutant flies look
      normal; the regulation of the bxd domain appears unaffected. Thus, the bxd
      noncoding RNA has no apparent function. 

PMID- 24077303
TI  - Mapping quantitative trait loci by controlling polygenic background effects.
AB  - A new mixed-model method was developed for mapping quantitative trait loci (QTL)
      by incorporating multiple polygenic covariance structures. First, we used genome
      wide markers to calculate six different kinship matrices. We then partitioned the
      total genetic variance into six variance components, one corresponding to each
      kinship matrix, including the additive, dominance, additive * additive, dominance
      * dominance, additive * dominance, and dominance * additive variances. The six
      different kinship matrices along with the six estimated polygenic variances were
      used to control the genetic background of a QTL mapping model. Simulation studies
      showed that incorporating epistatic polygenic covariance structure can improve
      QTL mapping resolution. The method was applied to yield component traits of rice.
      We analyzed four traits (yield, tiller number, grain number, and grain weight)
      using 278 immortal F2 crosses (crosses between recombinant inbred lines) and 1619
      markers. We found that the relative importance of each type of genetic variance
      varies across different traits. The total genetic variance of yield is
      contributed by additive * additive (18%), dominance * dominance (14%), additive *
      dominance (48%), and dominance * additive (15%) variances. Tiller number is
      contributed by additive (17%), additive * additive (22%), and dominance *
      additive (43%) variances. Grain number is mainly contributed by additive (42%),
      additive * additive (19%), and additive * dominance (31%) variances. Grain weight
      is almost exclusively contributed by the additive (73%) variance plus a small
      contribution from the additive * additive (10%) variance. Using the estimated
      genetic variance components to capture the polygenic covariance structure, we
      detected 39 effects for yield, 39 effects for tiller number, 24 for grain number,
      and 15 for grain weight. The new method can be directly applied to polygenic
      effect-adjusted genome-wide association studies (GWAS) in human and other
      species. 

PMID- 24077302
TI  - Initiation of meiotic recombination in Ustilago maydis.
AB  - A central feature of meiosis is the pairing and recombination of homologous
      chromosomes. Ustilago maydis, a biotrophic fungus that parasitizes maize, has
      long been utilized as an experimental system for studying recombination, but it
      has not been clear when in the life cycle meiotic recombination initiates. U.
      maydis forms dormant diploid teliospores as the end product of the infection
      process. Upon germination, teliospores complete meiosis to produce four haploid
      basidiospores. Here we asked whether the meiotic process begins when teliospores
      germinate or at an earlier stage in development. When teliospores homozygous for
      a cdc45 mutation temperature sensitive for DNA synthesis were germinated at the
      restrictive temperature, four nuclei became visible. This implies that
      teliospores have already undergone premeiotic DNA synthesis and suggests that
      meiotic recombination initiates at a stage of infection before teliospores
      mature. Determination of homologous recombination in plant tissue infected with
      U. maydis strains heteroallelic for the nar1 gene revealed that Nar(+)
      recombinants were produced at a stage before teliospore maturation. Teliospores
      obtained from a spo11Delta cross were still able to germinate but the process was
      highly disturbed and the meiotic products were imbalanced in chromosomal
      complement. These results show that in U. maydis, homologous recombination
      initiates during the infection process and that meiosis can proceed even in the
      absence of Spo11, but with loss of genomic integrity. 

PMID- 24077304
TI  - Gene amplification and functional diversification of melanocortin 4 receptor at
      an extremely polymorphic locus controlling sexual maturation in the platyfish.
AB  - In two swordtail species of the genus Xiphophorus, the onset of puberty has been
      shown to be modulated at the P locus by sequence polymorphism and gene copy
      number variation affecting the type 4 melanocortin hormone receptor Mc4r. The
      system works through the interaction of two allelic types, one encoding wild type
      and the other dominant-negative receptors. We have analyzed the structure and
      evolution of the P locus in the platyfish Xiphophorus maculatus, where as many as
      nine alleles of P determining the onset of sexual maturity in males and females,
      fecundity in females, and adult size in males are located on both the X and Y
      chromosomes in a region linked to the master sex-determining locus. In this
      species, mc4r has been amplified to up to 10 copies on both the X and Y
      chromosomes through recent large serial duplications. Subsequently, mc4r
      paralogues have diverged considerably into many different subtypes. Certain
      copies have acquired new untranslated regions through genomic rearrangements, and
      transposable element insertions and other mutations have accumulated in promoter
      regions, possibly explaining observed deviations from the classical mc4r
      transcriptional pattern. In the mc4r-coding sequence, in-frame insertions and
      deletions as well as nonsense and missense mutations have generated a high
      diversity of Mc4r-predicted proteins. Most of these variants are expressed in
      embryos, adults, and/or tumors. Functional receptor characterization demonstrated
      major divergence in pharmacological behavior for Mc4r receptors encoded by
      different copies of platyfish mc4r, with differences in constitutive activity as
      well as binding and stimulation by hormones. The high degree of allelic and copy
      number variation observed between individuals can explain the high level of
      polymorphism for sexual maturation, fecundity, and body size in the platyfish:
      multiple combinations of Mc4r variants with different biochemical properties
      might interact to modulate the melanocortin signaling that regulates the
      hypothalamus-pituitary-gonadal axis. 

PMID- 24077305
TI  - Adaptive divergence in experimental populations of Pseudomonas fluorescens. V.
      Insight into the niche specialist fuzzy spreader compels revision of the model
      Pseudomonas radiation.
AB  - Pseudomonas fluorescens is a model for the study of adaptive radiation. When
      propagated in a spatially structured environment, the bacterium rapidly
      diversifies into a range of niche specialist genotypes. Here we present a genetic
      dissection and phenotypic characterization of the fuzzy spreader (FS) morphotype
      a type that arises repeatedly during the course of the P. fluorescens radiation
      and appears to colonize the bottom of static broth microcosms. The causal
      mutation is located within gene fuzY (pflu0478)-the fourth gene of the five-gene
      fuzVWXYZ operon. fuzY encodes a beta-glycosyltransferase that is predicted to
      modify lipopolysaccharide (LPS) O antigens. The effect of the mutation is to
      cause cell flocculation. Analysis of 92 independent FS genotypes showed each to
      have arisen as the result of a loss-of-function mutation in fuzY, although
      different mutations have subtly different phenotypic and fitness effects.
      Mutations within fuzY were previously shown to suppress the phenotype of mat
      forming wrinkly spreader (WS) types. This prompted a reinvestigation of FS niche
      preference. Time-lapse photography showed that FS colonizes the meniscus of broth
      microcosms, forming cellular rafts that, being too flimsy to form a mat, collapse
      to the vial bottom and then repeatably reform only to collapse. This led to a
      reassessment of the ecology of the P. fluorescens radiation. Finally, we show
      that ecological interactions between the three dominant emergent types (smooth,
      WS, and FS), combined with the interdependence of FS and WS on fuzY, can, at
      least in part, underpin an evolutionary arms race with bacteriophage SBW25Phi2,
      to which mutation in fuzY confers resistance. 

PMID- 24077306
TI  - Tolerance of Escherichia coli to fluoroquinolone antibiotics depends on specific
      components of the SOS response pathway.
AB  - Bacteria exposed to bactericidal fluoroquinolone (FQ) antibiotics can survive
      without becoming genetically resistant. Survival of these phenotypically
      resistant cells, commonly called "persisters," depends on the SOS gene network.
      We have examined mutants in all known SOS-regulated genes to identify functions
      essential for tolerance in Escherichia coli. The absence of DinG and UvrD
      helicases and the Holliday junction processing enzymes RuvA and RuvB leads to a
      decrease in survival. Analysis of the respective mutants indicates that, in
      addition to repair of double-strand breaks, tolerance depends on the repair of
      collapsed replication forks and stalled transcription complexes. Mutation in recF
      results in increased survival, which identifies RecAF recombination as a
      poisoning mechanism not previously linked to FQ lethality. DinG acts upstream of
      SOS promoting its induction, whereas RuvAB participates in repair only. UvrD
      directly promotes all repair processes initiated by FQ-induced damage and
      prevents RecAF-dependent misrepair, making it one of the crucial SOS functions
      required for tolerance. 

PMID- 24077309
TI  - Chernobyl and Fukushima nuclear accidents: what has changed in the use of
      atmospheric dispersion modeling?
AB  - The threat of a major accidental or deliberate event that would lead to hazardous
      materials emission in the atmosphere is a great cause of concern to societies.
      This is due to the potential large scale of casualties and damages that could
      result from the release of explosive, flammable or toxic gases from industrial
      plants or transport accidents, radioactive material from nuclear power plants
      (NPPs), and chemical, biological, radiological or nuclear (CBRN) terrorist
      attacks. In order to respond efficiently to such events, emergency services and
      authorities resort to appropriate planning and organizational patterns. This
      paper focuses on the use of atmospheric dispersion modeling (ADM) as a support
      tool for emergency planning and response, to assess the propagation of the
      hazardous cloud and thereby, take adequate counter measures. This paper intends
      to illustrate the noticeable evolution in the operational use of ADM tools over
      25 y and especially in emergency situations. This study is based on data
      available in scientific publications and exemplified using the two most severe
      nuclear accidents: Chernobyl (1986) and Fukushima (2011). It appears that during
      the Chernobyl accident, ADM were used few days after the beginning of the
      accident mainly in a diagnosis approach trying to reconstruct what happened,
      whereas 25 y later, ADM was also used during the first days and weeks of the
      Fukushima accident to anticipate the potentially threatened areas. We argue that
      the recent developments in ADM tools play an increasing role in emergencies and
      crises management, by supporting stakeholders in anticipating, monitoring and
      assessing post-event damages. However, despite technological evolutions, its
      prognostic and diagnostic use in emergency situations still arise many issues. 

PMID- 24077307
TI  - Regulation of Toll signaling and inflammation by beta-arrestin and the SUMO
      protease Ulp1.
AB  - The Toll signaling pathway has a highly conserved function in innate immunity and
      is regulated by multiple factors that fine tune its activity. One such factor is
      beta-arrestin Kurtz (Krz), which we previously implicated in the inhibition of
      developmental Toll signaling in the Drosophila melanogaster embryo. Another level
      of controlling Toll activity and immune system homeostasis is by protein
      sumoylation. In this study, we have uncovered a link between these two modes of
      regulation and show that Krz affects sumoylation via a conserved protein
      interaction with a SUMO protease, Ulp1. Loss of function of krz or Ulp1 in
      Drosophila larvae results in a similar inflammatory phenotype, which is
      manifested as increased lamellocyte production; melanotic mass formation; nuclear
      accumulation of Toll pathway transcriptional effectors, Dorsal and Dif; and
      expression of immunity genes, such as Drosomycin. Moreover, mutations in krz and
      Ulp1 show dosage-sensitive synergistic genetic interactions, suggesting that
      these two proteins are involved in the same pathway. Using Dorsal sumoylation as
      a readout, we found that altering Krz levels can affect the efficiency of SUMO
      deconjugation mediated by Ulp1. Our results demonstrate that beta-arrestin
      controls Toll signaling and systemic inflammation at the level of sumoylation. 

PMID- 24077308
TI  - Evidence for tissue-specific Jak/STAT target genes in Drosophila optic lobe
      development.
AB  - The evolutionarily conserved JAK/STAT pathway plays important roles in
      development and disease processes in humans. Although the signaling process has
      been well established, we know relatively little about what the relevant target
      genes are that mediate JAK/STAT activation during development. Here, we have used
      genome-wide microarrays to identify JAK/STAT targets in the optic lobes of the
      Drosophila brain and identified 47 genes that are positively regulated by
      JAK/STAT. About two-thirds of the genes encode proteins that have orthologs in
      humans. The STAT targets in the optic lobe appear to be different from the
      targets identified in other tissues, suggesting that JAK/STAT signaling may
      regulate different target genes in a tissue-specific manner. Functional analysis
      of Nop56, a cell-autonomous STAT target, revealed an essential role for this gene
      in the growth and proliferation of neuroepithelial stem cells in the optic lobe
      and an inhibitory role in lamina neurogenesis. 

PMID- 24077310
TI  - Too much of a good thing....

PMID- 24077311
TI  - Increased prevalence of Trichomonas vaginalis in mid-aged women is linked to
      sexual activity and not to hormonal changes.

PMID- 24077312
TI  - Reply to letter: increased prevalence of Trichomonas vaginalis in mid-aged women
      is linked to sexual activity and not to hormonal changes.

PMID- 24077313
TI  - Using cognitive task analysis to create a teaching protocol for bovine dystocia.
AB  - When learning skilled techniques and procedures, students face many challenges.
      Learning is easier when detailed instructions are available, but experts often
      find it difficult to articulate all of the steps involved in a task or relate to
      the learner as a novice. This problem is further compounded when the technique is
      internal and unsighted (e.g., obstetrical procedures). Using expert bovine
      practitioners and a life-size model cow and calf, the steps and decision making
      involved in performing correction of two different dystocia presentations
      (anterior leg back and breech) were deconstructed using cognitive task analysis
      (CTA). Video cameras were positioned to capture movement inside and outside the
      cow model while the experts were asked to first perform the technique as they
      would in a real situation and then perform the procedure again as if articulating
      the steps to a novice learner. The audio segments were transcribed and, together
      with the video components, analyzed to create a list of steps for each expert.
      Consensus was achieved between experts during individual interviews followed by a
      group discussion. A "gold standard" list or teaching protocol was created for
      each malpresentation. CTA was useful in defining the technical and cognitive
      steps required to both perform and teach the tasks effectively. Differences
      between experts highlight the need for consensus before teaching the skill. In
      addition, the study identified several different, yet effective, techniques and
      provided information that could allow experts to consider other approaches they
      might use when their own technique fails. 

PMID- 24077314
TI  - Team-based learning increases active engagement and enhances development of
      teamwork and communication skills in a first-year course for veterinary and
      animal science undergraduates.
AB  - Team-based learning (TBL) was implemented into a first-year course (Principles in
      Animal Behaviour, Welfare and Ethics) for BSc Veterinary Bioscience (VB) and
      Animal Science (AS) students. TBL is now used widely in teaching medical
      students, but has had more limited uptake in veterinary education. This study
      reports its use over 2 years with cohorts of 126 and 138 students in 2011 and
      2012, respectively. Average individual marks for multiple-choice question (MCQ)
      tests in the Readiness Assurance component of TBL were higher for the teams than
      for individuals for each session, explicitly demonstrating the advantages of
      teamwork. Students reported that they felt actively involved and that TBL helped
      them both with their learning and in developing other important skills, such as
      teamwork and communication. Qualitative analysis of written feedback from the
      students revealed positive themes of discussion, application, revelation,
      socializing, engagement, clarification, and retention/revision. In 2011 negative
      comments included the need to shorten the TBL sessions, but in 2012 tightening of
      the timelines meant that this was no longer a major concern. Requests to provide
      better introductory and background materials and ambiguity in questions in the
      TBL activities were what students least liked about the TBL. However, most
      comments were positive rather than negative in nature, and many students
      preferred the TBL to lectures. With requirements for curricula to teach
      professional skills, such as communication and teamwork, and the positive results
      from TBL's implementation, it is hoped that this study will encourage others to
      trial the use of TBL in veterinary education. 

PMID- 24077316
TI  - Electrical resistivity-based study of self-sensing properties for shape memory
      alloy-actuated artificial muscle.
AB  - Shape memory alloy (SMA) has great potential to develop light and compact
      artificial muscle (AM) due to its muscle-like high power-to-weight ratio,
      flexibility and silent operation properties. In this paper, SMA self-sensing
      properties are explored and modeled in depth to imitate the integrated muscle
      like functions of actuating and self-sensing for SMA-AM based on the
      investigation of SMA electrical resistivity (ER). Firstly, an ER transformation
      kinetics model is proposed based on the simulation of SMA differential scanning
      calorimetry (DSC) curves. Then a series of thermal-electrical-mechanical
      experiments are carried out to verify the validity of the ER model, whereby the
      SMA-AM self-sensing function is well established under different stress
      conditions. Finally the self-sensing capability is further demonstrated by its
      application to a novel SMA-AM-actuated active ankle-foot orthosis (AAFO). 

PMID- 24077317
TI  - A low density microarray method for the identification of human papillomavirus
      type 18 variants.
AB  - We describe a novel microarray based-method for the screening of oncogenic human
      papillomavirus 18 (HPV-18) molecular variants. Due to the fact that sequencing
      methodology may underestimate samples containing more than one variant we
      designed a specific and sensitive stacking DNA hybridization assay. This
      technology can be used to discriminate between three possible phylogenetic
      branches of HPV-18. Probes were attached covalently on glass slides and
      hybridized with single-stranded DNA targets. Prior to hybridization with the
      probes, the target strands were pre-annealed with the three auxiliary contiguous
      oligonucleotides flanking the target sequences. Screening HPV-18 positive cell
      lines and cervical samples were used to evaluate the performance of this HPV DNA
      microarray. Our results demonstrate that the HPV-18's variants hybridized
      specifically to probes, with no detection of unspecific signals. Specific probes
      successfully reveal detectable point mutations in these variants. The present DNA
      oligoarray system can be used as a reliable, sensitive and specific method for
      HPV-18 variant screening. Furthermore, this simple assay allows the use of
      inexpensive equipment, making it accessible in resource-poor settings. 

PMID- 24077318
TI  - Highly selective fluorescent sensing of proteins based on a fluorescent
      molecularly imprinted nanosensor.
AB  - A fluorescent molecularly imprinted nanosensor was obtained by grafting imprinted
      polymer onto the surface of multi-wall carbon nanotubes and post-imprinting
      treatment with fluorescein isothiocyanate (FITC). The fluorescence of lysozyme
      imprinted polymer (Lys-MIP) was quenched more strongly by Lys than that of
      nonimprinted polymer (NIP), which indicated that the Lys-MIP could recognize Lys.
      The resulted imprinted material has the ability to selectively sense a target
      protein, and an imprinting factor of 3.34 was achieved. The Lys-MIP also showed
      selective detection for Lys among other proteins such as cytochrome C (Cyt C),
      hemoglobin (HB) and bovine serum albumin (BSA) due to the imprinted sites in the
      Lys-MIP. This approach combines the high selectivity of surface molecular
      imprinting technology and fluorescence, and converts binding events into
      detectable signals by monitoring fluorescence spectra. Therefore, it will have
      further applications for Lys sensing. 

PMID- 24077319
TI  - Assessing routing strategies for cognitive radio sensor networks.
AB  - Interest in the cognitive radio sensor network (CRSN) paradigm has gradually
      grown among researchers. This concept seeks to fuse the benefits of dynamic
      spectrum access into the sensor network, making it a potential player in the next
      generation (NextGen) network, which is characterized by ubiquity. Notwithstanding
      its massive potential, little research activity has been dedicated to the network
      layer. By contrast, we find recent research trends focusing on the physical
      layer, the link layer and the transport layers. The fact that the cross-layer
      approach is imperative, due to the resource-constrained nature of CRSNs, can make
      the design of unique solutions non-trivial in this respect. This paper seeks to
      explore possible design opportunities with wireless sensor networks (WSNs),
      cognitive radio ad-hoc networks (CRAHNs) and cross-layer considerations for
      implementing viable CRSN routing solutions. Additionally, a detailed performance
      evaluation of WSN routing strategies in a cognitive radio environment is
      performed to expose research gaps. With this work, we intend to lay a foundation
      for developing CRSN routing solutions and to establish a basis for future work in
      this area. 

PMID- 24077320
TI  - Simple and rapid determination of ferulic acid levels in food and cosmetic
      samples using paper-based platforms.
AB  - Ferulic acid is an important phenolic antioxidant found in or added to diet
      supplements, beverages, and cosmetic creams. Two designs of paper-based platforms
      for the fast, simple and inexpensive evaluation of ferulic acid contents in food
      and pharmaceutical cosmetics were evaluated. The first, a paper-based
      electrochemical device, was developed for ferulic acid detection in uncomplicated
      matrix samples and was created by the photolithographic method. The second, a
      paper-based colorimetric device was preceded by thin layer chromatography (TLC)
      for the separation and detection of ferulic acid in complex samples using a
      silica plate stationary phase and an 85:15:1 (v/v/v) chloroform: methanol: formic
      acid mobile phase. After separation, ferulic acid containing section of the TLC
      plate was attached onto the patterned paper containing the colorimetric reagent
      and eluted with ethanol. The resulting color change was photographed and
      quantitatively converted to intensity. Under the optimal conditions, the limit of
      detection of ferulic acid was found to be 1 ppm and 7 ppm (S/N = 3) for first and
      second designs, respectively, with good agreement with the standard HPLC-UV
      detection method. Therefore, these methods can be used for the simple, rapid,
      inexpensive and sensitive quantification of ferulic acid in a variety of samples.

PMID- 24077321
TI  - Autonomic nervous system responses can reveal visual fatigue induced by 3D
      displays.
AB  - Previous research has indicated that viewing 3D displays may induce greater
      visual fatigue than viewing 2D displays. Whether viewing 3D displays can evoke
      measureable emotional responses, however, is uncertain. In the present study, we
      examined autonomic nervous system responses in subjects viewing 2D or 3D
      displays. Autonomic responses were quantified in each subject by heart rate,
      galvanic skin response, and skin temperature. Viewers of both 2D and 3D displays
      showed strong positive correlations with heart rate, which indicated little
      differences between groups. In contrast, galvanic skin response and skin
      temperature showed weak positive correlations with average difference between
      viewing 2D and 3D. We suggest that galvanic skin response and skin temperature
      can be used to measure and compare autonomic nervous responses in subjects
      viewing 2D and 3D displays. 

PMID- 24077322
TI  - Fast and sensitive detection of Pb2+ in foods using disposable screen-printed
      electrode modified by reduced graphene oxide.
AB  - In this study, reduced graphene oxide (rGO) was electrochemically deposited on
      the surface of screen-printed carbon electrodes (SPCE) to prepare a disposable
      sensor for fast detection of Pb2+ in foods. The SEM images showed that the rGO
      was homogeneously deposited onto the electrode surface with a wrinkled
      nanostructure, which provided 2D bridges for electron transport and a larger
      active area for Pb2+ adsorption. Results showed that rGO modification enhanced
      the activity of the electrode surface, and significantly improved the
      electrochemical properties of SPCE. The rGO modified SPCE (rGO-SPCE) was applied
      to detect Pb2+ in standard aqueous solution, showing a sharp stripping peak and a
      relatively constant peak potential in square wave anodic stripping voltammetry
      (SWASV). The linear range for Pb2+ detection was 5~200 ppb (R2 = 0.9923) with a
      low detection limit of 1 ppb (S/N = 3). The interference of Cd2+ and Cu2+ at low
      concentrations was effectively avoided. Finally, the rGO-SPCE was used for
      determination of lead in real tap water, juice, preserved eggs and tea samples.
      Compared with results from graphite furnace atomic absorption spectroscopy
      (GFAAS), the results based on rGO-SPCE were both accurate and reliable,
      suggesting that the disposable sensor has great potential in application for
      fast, sensitive and low-cost detection of Pb2+ in foods. 

PMID- 24077323
TI  - A temperature sensor based on a polymer optical fiber macro-bend.
AB  - The design and development of a plastic optical fiber (POF) macrobend temperature
      sensor is presented. The sensor has a linear response versus temperature at a
      fixed bend radius, with a sensitivity of . The sensor system used a dummy fiber
      optic sensor for reference purposes having a resolution below 0.3  degrees C. A
      comprehensive experimental analysis was carried out to provide insight into the
      effect of different surrounding media on practical macro-bend POF sensor
      implementation. Experimental results are successfully compared with bend loss
      calculations. 

PMID- 24077324
TI  - The association of brachial artery diameter with noncalcified coronary plaque
      burden in apparently healthy individuals.
AB  - OBJECTIVE: Coronary atherosclerosis has been associated with systemic arterial
      remodeling even in nonatherosclerotic vessels. However, it is not known whether
      systemic remodeling is differentially associated with the cumulative
      atherosclerotic process, reflected by putatively quiescent calcified plaque (CP),
      or with active atherosclerosis, consisting of noncalcified plaque (NCP). We thus
      examined the association of brachial artery diameter (BAD), an artery that does
      not suffer clinical atherosclerosis, with the presence and the extent of coronary
      CP and NCP. METHODS: We studied 688 apparently healthy, asymptomatic participants
      from 350 families with a history of early-onset coronary artery disease (<60
      years of age) by measuring coronary artery disease risk factors and coronary
      plaque using dual-source computed tomographic angiography. Plaque volumes were
      quantified using a validated automated method. BAD was measured during diastole
      using B-mode ultrasound. The association of resting BAD with any detectable
      plaque, and log-transformed CP and NCP volumes if detectable, was tested using
      generalized estimating equations adjusted for age, sex, race, current smoking,
      diabetes, hypertension, BMI, and non-HDL and HDL cholesterol. RESULTS: Higher
      quintiles of BAD were associated with greater age and male sex (both P<0.001). In
      the fully adjusted analysis, CP volume was not associated with BAD (P=0.65) but a
      1 ml greater NCP volume was associated with a 0.65 mm larger BAD (P=0.027).
      CONCLUSION: Our results suggest that systemic arterial remodeling of
      nonatherosclerotic arteries is a dynamic process that is correlated with the
      extent of putatively active atherosclerotic processes in distant beds but not
      with inactive accumulated plaque burden.

PMID- 24077325
TI  - Cytochrome c release in acute myocardial infarction predicts poor prognosis and
      myocardial reperfusion on contrast-enhanced magnetic resonance imaging.
AB  - BACKGROUND: Myocardial ischemia and reperfusion injury in ST-segment elevation
      myocardial infarction (STEMI) can trigger no-flow, resulting in myocardial
      necrosis and apoptosis, even a poor prognosis. Cytochrome c can induce an
      apoptotic process. The aim of our study was to assess the relationship between
      systemic cytochrome c levels and the occurrence of no-reflow in STEMI. METHODS:
      One hundred and sixty patients with STEMI undergoing a primary percutaneous
      coronary intervention (PPCI) were randomly chosen. Patients were divided into two
      groups defined by the mean cytochrome c peak level after PPCI. No-reflow was
      assessed using three different methods after PPCI: myocardial blush grade,
      electrocardiographic ST-resolution, and microvascular obstruction (MO) assessed
      by cardiovascular magnetic resonance imaging. The primary clinical end points
      were major adverse cardiovascular events (defined as cardiac death, reinfarction,
      or new congestive heart failure). Clinical follow-up was carried out for 1 year.
      RESULTS: Patients with a cytochrome c level of at least the mean peak level had a
      greater creatine kinase-MB isoenzyme peak level (P=0.044), a lower left
      ventricular ejection fraction (P=0.029), a significantly higher occurrence of
      early MO (P=0.008), and a significantly larger extent of early MO (P=0.020). The
      cytochrome c peak level was elevated in patients with early MO (P=0.025),
      myocardial blush grade 0-1 (P=0.002), and ST-resolution less than 30% (P=0.003)
      after PPCI. A higher incidence of cardiac death at the 1-year follow-up was found
      in the patients with cytochrome c levels of at least the mean peak level (log
      rank, P=0.029). CONCLUSION: Cytochrome c levels above the mean peak level were
      related to no-reflow and mortality in patients with STEMI.

PMID- 24077326
TI  - The relationship of plasma neuropeptide Y levels with coronary collateral
      development.
AB  - OBJECTIVE: Neuropeptide Y (NPY), a sympathetic cotransmitter, has been shown to
      promote angiogenesis in in-vitro models. The aim of this study was to evaluate
      the relationship of plasma NPY levels with coronary collateral vessel development
      in patients with coronary artery disease. METHODS: The study included 81 patients
      with at least one coronary stenosis with at least 80% narrowing in coronary
      angiography. Collateral vessels were graded according to the Rentrop
      classification. The study patients were divided into two groups, namely patients
      with well-developed collaterals and patients with poorly developed collaterals.
      Well-developed collaterals were defined as Rentrop collateral score of at least
      2. Plasma levels of NPY, vascular endothelial growth factor, fibroblast growth
      factor, and noradrenaline were measured using an enzyme-linked immunosorbent
      assay. RESULTS: Plasma NPY was significantly higher in patients with well
      developed collaterals as compared with patients with poorly developed collaterals
      (P=0.026). In contrast, plasma noradrenaline was significantly lower in patients
      with well-developed collaterals (P=0.022). There was no statistically significant
      difference in vascular endothelial growth factor and fibroblast growth factor
      levels between groups. The NPY level was positively correlated with the presence
      of diabetes (r=0.528, P<0.001). The extent of coronary artery disease (Gensini
      score) was significantly higher in patients with well-developed collaterals
      (P<0.001). After confounding variables were controlled for, the NPY level in
      patients with well-developed collaterals was significantly higher than those
      patients with poorly developed collaterals. CONCLUSION: In this study, NPY levels
      were found to be significantly higher in patients with well-developed coronary
      collaterals compared with patients with poorly developed collaterals. New studies
      are needed to show whether this relationship is causal.

PMID- 24077327
TI  - Nanoparticle accumulation and transcytosis in brain endothelial cell layers.
AB  - The blood-brain barrier (BBB) is a selective barrier, which controls and limits
      access to the central nervous system (CNS). The selectivity of the BBB relies on
      specialized characteristics of the endothelial cells that line the
      microvasculature, including the expression of intercellular tight junctions,
      which limit paracellular permeability. Several reports suggest that nanoparticles
      have a unique capacity to cross the BBB. However, direct evidence of nanoparticle
      transcytosis is difficult to obtain, and we found that typical transport studies
      present several limitations when applied to nanoparticles. In order to
      investigate the capacity of nanoparticles to access and transport across the BBB,
      several different nanomaterials, including silica, titania and albumin- or
      transferrin-conjugated gold nanoparticles of different sizes, were exposed to a
      human in vitro BBB model of endothelial hCMEC/D3 cells. Extensive transmission
      electron microscopy imaging was applied in order to describe nanoparticle
      endocytosis and typical intracellular localisation, as well as to look for
      evidence of eventual transcytosis. Our results show that all of the nanoparticles
      were internalised, to different extents, by the BBB model and accumulated along
      the endo-lysosomal pathway. Rare events suggestive of nanoparticle transcytosis
      were also observed for several of the tested materials. 

PMID- 24077329
TI  - Arthropod fossil data increase congruence of morphological and molecular
      phylogenies.
AB  - The relationships of major arthropod clades have long been contentious, but
      refinements in molecular phylogenetics underpin an emerging consensus.
      Nevertheless, molecular phylogenies have recovered topologies that morphological
      phylogenies have not, including the placement of hexapods within a paraphyletic
      Crustacea, and an alliance between myriapods and chelicerates. Here we show
      enhanced congruence between molecular and morphological phylogenies based on 753
      morphological characters for 309 fossil and Recent panarthropods. We resolve
      hexapods within Crustacea, with remipedes as their closest extant relatives, and
      show that the traditionally close relationship between myriapods and hexapods is
      an artefact of convergent character acquisition during terrestrialisation. The
      inclusion of fossil morphology mitigates long-branch artefacts as exemplified by
      pycnogonids: when fossils are included, they resolve with euchelicerates rather
      than as a sister taxon to all other euarthropods.

PMID- 24077330
TI  - Appetitive and Defensive Motivation: Goal-Directed or Goal-Determined?
AB  - Our view is that fundamental appetitive and defensive motivation systems evolved
      to mediate a complex array of adaptive behaviors that support the organism's
      drive to survive-defending against threat and securing resources. Activation of
      these motive systems engages processes that facilitate attention allocation,
      information intake, sympathetic arousal, and, depending on context, will prompt
      tactical actions that can be directed either toward or away from the strategic
      goal, whether defensively or appetitively determined. Research from our
      laboratory that measures autonomic, central, and somatic reactions when
      processing emotional scenes is described which indicates that motivationally
      relevant cues, whether appetitive or defensive, capture attention preferentially,
      prompt enhanced perceptual processing and information gathering, and occasion
      metabolic arousal that mobilizes the organism for coping actions.

PMID- 24077328
TI  - Nuclear targeting of dystroglycan promotes the expression of androgen regulated
      transcription factors in prostate cancer.
AB  - Dystroglycan is frequently lost in adenocarcinoma, but the mechanisms and
      consequences are poorly understood. We report an analysis of beta-dystroglycan in
      prostate cancer in human tissue samples and in LNCaP cells in vitro. There is
      progressive loss of beta-dystroglycan immunoreactivity from basal and lateral
      surfaces of prostate epithelia which correlates significantly with increasing
      Gleason grade. In about half of matched bone metastases there is significant
      dystroglycan re-expression. In tumour tissue and in LNCaP cells there is also a
      tyrosine phosphorylation-dependent translocation of beta-dystroglycan to the
      nucleus. Analysis of gene expression data by microarray, reveals that nuclear
      targeting of beta-dystroglycan in LNCaP cells alters the transcription of
      relatively few genes, the most unregulated being the transcription factor ETV1.
      These data suggest that proteolysis, tyrosine phosphorylation and translocation
      of dystroglycan to the nucleus resulting in altered gene transcription could be
      important mechanisms in the progression of prostate cancer. 

PMID- 24077331
TI  - Temperament and the Development of Conscience: The Moderating Role of Effortful
      Control.
AB  - In this longitudinal study we examined whether two components of effortful
      control, behavioral control and executive function, moderated the relation
      between temperament and conscience development. Temperament was assessed when
      participants were 2 years of age, and three temperament groups were formed;
      inhibited, exuberant, and low reactive. At 4.5 years of age children's behavioral
      control and executive function were assessed. Moral behavior, emotionality during
      an empathy film, and false-belief understanding were measured at 5.5 years of age
      as components of conscience. Results indicate that inhibited children may benefit
      most from higher levels of effortful control. Inhibited children with higher
      levels of behavioral control performed better on false-belief understanding tasks
      whereas inhibited children who scored higher on executive function tests reported
      less emotional response to the evocative film. Finally, as a group, inhibited
      children exhibited more moral behavior than exuberant and low reactive children.

PMID- 24077332
TI  - A stable isotope approach for source apportionment of chlorinated ethene plumes
      at a complex multi-contamination events urban site.
AB  - The stable carbon isotope composition of chlorinated aliphatic compounds such as
      chlorinated methanes, ethanes and ethenes was examined as an intrinsic
      fingerprint for apportionment of sources. A complex field site located in Ferrara
      (Italy), with more than 50years history of use of chlorinated aliphatic
      compounds, was investigated in order to assess contamination sources. Several
      contamination plumes were found in a complex alluvial sandy multi-aquifer system
      close to the river Po; sources are represented by uncontained former industrial
      and municipal dump sites as well as by spills at industrial areas. The carbon
      stable isotope signature allowed distinguishing 2 major sources of contaminants.
      One source of chlorinated aliphatic contaminants was strongly depleted in 13C (<
      600/00) suggesting production lines which have used depleted methane for
      synthesis. The other source had typical carbon isotope compositions of >-400/00
      which is commonly observed in recent production of chlorinated solvents. The
      degradation processes in the plumes could be traced interpreting the isotope
      enrichment and depletion of parent and daughter compounds, respectively. We
      demonstrate that, under specific production conditions, namely when highly
      chlorinated ethenes are produced as by-product during chloromethanes production,
      13C depleted fingerprinting of contaminants can be obtained and this can be used
      to track sources and address the responsible party of the pollution in urban
      areas.

PMID- 24077334
TI  - Alcohol licensing data: why is it an underused resource in public health?
AB  - Alcohol-related harm is related to alcohol availability. Due to complex
      regulatory and environmental factors, alcohol availability varies spatially.
      However, the extent of this variation is largely unknown in the UK, despite its
      potential influence on patterns of alcohol-related harm. We investigate why
      administrative data is underused in the study of alcohol-related harm in the UK.
      We found that local authorities routinely collect a rich supply of licensing
      data. However, this information is stored in databases that are sometimes
      difficult to access. With greater coordination between researchers and
      practitioners, this data can be used to fulfil its primary administrative purpose
      and also contribute to understanding and prevention of alcohol-related health and
      social problems. 

PMID- 24077333
TI  - C-N bond forming cross-coupling reactions: an overview.
AB  - Nitrogen containing compounds are of great importance because of their
      interesting and diverse biological activities. The construction of the C-N bond
      is of significant importance as it opens avenues for the introduction of nitrogen
      in organic molecules. Despite significant advancements in this field, the
      construction of the C-N bond is still a major challenge for organic chemists, due
      to the involvement of harsh reaction conditions or the use of expensive catalysts
      in many cases. Thus, it is a challenge to develop alternative, milder and cheaper
      methodologies for the construction of C-N bonds. Herein, we have selected some
      prime literature reports that may serve this purpose. 

PMID- 24077335
TI  - Measuring spatial accessibility to healthcare for populations with multiple
      transportation modes.
AB  - Few measures of healthcare accessibility have considered multiple transportation
      modes when people seek healthcare. Based on the framework of the 2 Step Floating
      Catchment Area Method (2SFCAM), we proposed an innovative method to incorporate
      transportation modes into the accessibility estimation. Taking Florida, USA, as a
      study area, we illustrated the implementation of the multi-mode 2SFCAM, and
      compared the accessibility estimates with those from the traditional single-mode
      2SFCAM. The results suggest that the multi-modal method, by accounting for
      heterogeneity in populations, provides more realistic accessibility estimations,
      and thus offers a better guidance for policy makers to mitigate health inequity
      issues. 

PMID- 24077336
TI  - Time evolution of luminescence of Sr2SiO4:Eu2+.
AB  - In this contribution, the photoluminescence, time-resolved luminescence and
      luminescence kinetics of alpha'-Sr2SiO4:Eu(2+) are studied. The luminescence of
      Sr2SiO4:Eu(2+) consists of two broad bands, peaked at 490 nm (blue-green) and 570
      nm (yellow-orange), which originate from two luminescence centers, related to
      Eu(2+) in ten-coordinated SI and nine-coordinated SII sites, respectively. Based
      on spectroscopic data the energetic structure of Sr2SiO4:Eu(2+) has been
      developed, which includes the bands edges, energies of Eu(2+) in the SI and SII
      sites and energies of strontium and oxygen vacancies. To investigate the long
      lasting luminescence phenomenon in Sr2SiO4:Eu(2+) the temperature influence on
      the time evolution of luminescence was analyzed. It has been found that the long
      lasting luminescence is related to the Eu(2+) in SII site. The shallowest traps
      responsible for emission decaying within a few seconds are tentatively attributed
      to the [Eu(3+)(SII)-[Formula: see text]] centers. The depth of traps responsible
      for the long-lasting luminescence observed at room temperature has been estimated
      as equal 0.73 eV.

PMID- 24077337
TI  - Revision of total knee arthroplasty in a patient with contralateral transfemoral
      amputation: case report.
AB  - BACKGROUND: Knee arthroplasty is an efficient solution for osteoarthrosis in
      amputees. However, because of overload on the implant, it is apparently more
      subject to failure than in the non-amputated population. The aim of this case
      report is to show a failure of primary total knee arthroplasty contralateral to
      transfemoral amputation that required revision involving a tissue bank because of
      severely compromised knee bone. Surgical strategies, rehabilitation, and
      postoperative care for the operated limb and the contralateral prosthesis were
      demonstrated. CASE DESCRIPTION AND METHODS: A 60-year-old patient with early
      failure of total knee arthroplasty contralateral to transfemoral amputation
      underwent arthroplasty revision in which a graft from a tissue bank was used.
      After the revision, prosthesis length adjustment and exercise therapy were
      fundamental to the rehabilitation. FINDINGS AND OUTCOMES: The patient progressed
      well after the revision of the arthroplasty, with increases on the Knee Society
      Score and 36-Item Short Form Health Survey scales. CONCLUSION: Knee arthroplasty
      in amputees should be planned differently to that of the general population. For
      the procedure to be successful, there should be greater attention to implant
      stability, equalization of leg length, and a postoperative regimen including
      muscle strengthening and range of motion exercises to achieve the required knee
      flexion. CLINICAL RELEVANCE: This case report is important because it presents a
      challenging case of a unilateral transfemoral amputee with failed arthroplasty
      over the years in the contralateral limb. To our knowledge, such a case has not
      been described in the scientific literature. It would be helpful for surgeons and
      rehabilitation professionals to chart out a treatment protocol and also to
      prevent premature failure of the joint.

PMID- 24077338
TI  - Energy- and time-resolved detection of prompt gamma-rays for proton range
      verification.
AB  - In this work, we present experimental results of a novel prompt gamma-ray
      detector for proton beam range verification. The detection system features an
      actively shielded cerium-doped lanthanum(III) bromide scintillator, coupled to a
      digital data acquisition system. The acquisition was synchronized to the
      cyclotron radio frequency to separate the prompt gamma-ray signals from the later
      arriving neutron-induced background. We designed the detector to provide a high
      energy resolution and an effective reduction of background events, enabling
      discrete proton-induced prompt gamma lines to be resolved. Measuring discrete
      prompt gamma lines has several benefits for range verification. As the discrete
      energies correspond to specific nuclear transitions, the magnitudes of the
      different gamma lines have unique correlations with the proton energy and can be
      directly related to nuclear reaction cross sections. The quantification of
      discrete gamma lines also enables elemental analysis of tissue in the beam path,
      providing a better prediction of prompt gamma-ray yields. We present the results
      of experiments in which a water phantom was irradiated with proton pencil-beams
      in a clinical proton therapy gantry. A slit collimator was used to collimate the
      prompt gamma-rays, and measurements were performed at 27 positions along the path
      of proton beams with ranges of 9, 16 and 23 g cm(-2) in water. The magnitudes of
      discrete gamma lines at 4.44, 5.2 and 6.13 MeV were quantified. The prompt gamma
      lines were found to be clearly resolved in dimensions of energy and time, and had
      a reproducible correlation with the proton depth-dose curve. We conclude that the
      measurement of discrete prompt gamma-rays for in vivo range verification of
      clinical proton beams is feasible, and plan to further study methods and detector
      designs for clinical use.

PMID- 24077339
TI  - Body mass index, physical activity, and fracture among young adults: longitudinal
      results from the Thai cohort study.
AB  - BACKGROUND: We investigated risk factors for fracture among young adults,
      particularly body mass index (BMI) and physical activity, which although
      associated with fracture in older populations have rarely been investigated in
      younger people. METHODS: In 2009, 4 years after initial recruitment, 58 204 Thais
      aged 19 to 49 years were asked to self-report fractures incident in the preceding
      4 years. Conditional logistic regression was used to calculate odds ratios (ORs)
      and 95% CIs for associations of fracture incidence with baseline BMI and physical
      activity. RESULTS: Very obese women had a 70% increase in fracture risk (OR =
      1.73, 95% CI 1.21-2.46) as compared with women with a normal BMI. Fracture risk
      increased by 15% with every 5-kg/m(2) increase in BMI. The effects were strongest
      for fractures of the lower limbs. Frequent purposeful physical activity was also
      associated with increased fracture risk among women (OR = 1.52, 95% CI 1.12-2.06
      for 15 episodes/week vs none). Neither BMI nor physical activity was associated
      with fracture among men, although fracture risk decreased by 4% with every
      additional 2 hours of average sitting time per day (OR = 0.96, 95% CI 0.93-0.99).
      CONCLUSIONS: The increase in obesity prevalence will likely increase fracture
      burden among young women but not young men. While active lifestyles have health
      benefits, our results highlight the importance of promoting injury prevention
      practices in conjunction with physical activity recommendations, particularly
      among women.

PMID- 24077340
TI  - Association of inflammatory gene polymorphisms and conventional risk factors with
      arterial stiffness by age.
AB  - BACKGROUND: Inflammatory gene polymorphisms are potentially associated with
      atherosclerosis risk, but their age-related effects are unclear. To investigate
      the age-related effects of inflammatory gene polymorphisms on arterial stiffness,
      we conducted cross-sectional and 5-year follow-up studies using the cardio-ankle
      vascular index (CAVI) as a surrogate marker of arterial stiffness. METHODS: We
      recruited 1850 adults aged 34 to 69 years from the Japanese general population.
      Inflammatory gene polymorphisms were selected from NF-kB1, CD14, IL-6, IL-10, MCP
      1, ICAM-1, and TNF-alpha. Associations of CAVI with genetic and conventional risk
      factors were estimated by sex and age group (34-49, 50-59, and 60-69 years) using
      a general linear model. The association with 5-year change in CAVI was examined
      longitudinally. RESULTS: Glucose intolerance was associated with high CAVI among
      women in all age groups, while hypertension was associated with high CAVI among
      participants in all age groups, except younger women. Mean CAVI for the CD14 CC
      genotype was lower than those for the TT and CT genotypes (P for trend = 0.005),
      while the CD14 polymorphism was associated with CAVI only among men aged 34 to 49
      years (P = 0.006). No association of the other 6 polymorphisms with CAVI was
      observed. No association with 5-year change in CAVI was apparent. CONCLUSIONS:
      Inflammatory gene polymorphisms were not associated with arterial stiffness. To
      confirm these results, further large-scale prospective studies are warranted.

PMID- 24077341
TI  - Analysis of petroleum-contaminated soils by diffuse reflectance spectroscopy and
      sequential ultrasonic solvent extraction-gas chromatography.
AB  - In this study, we demonstrate that partial least-squares regression analysis with
      full cross-validation of spectral reflectance data estimates the amount of
      polycyclic aromatic hydrocarbons in petroleum-contaminated tropical rainforest
      soils. We applied the approach to 137 field-moist intact soil samples collected
      from three oil spill sites in Ogoniland in the Niger Delta province (5.317
      degrees N, 6.467 degrees E), Nigeria. We used sequential ultrasonic solvent
      extraction-gas chromatography as the reference chemical method. We took soil
      diffuse reflectance spectra with a mobile fibre-optic visible and near-infrared
      spectrophotometer (350-2500 nm). Independent validation of combined data from
      studied sites showed reasonable prediction precision (root-mean-square error of
      prediction = 1.16-1.95 mg kg(-1), ratio of prediction deviation = 1.86-3.12, and
      validation r(2) = 0.77-0.89). This suggests that the methodology may be useful
      for rapid assessment of the spatial variability of polycyclic aromatic
      hydrocarbons in petroleum-contaminated soils in the Niger Delta to inform risk
      assessment and remediation. 

PMID- 24077342
TI  - Short- and medium-term prognosis in patients hospitalized for COPD exacerbation:
      the CODEX index.
AB  - BACKGROUND: No valid tools exist for evaluating the prognosis in the short and
      medium term after hospital discharge of patients with COPD. Our hypothesis was
      that a new index based on the CODEX (comorbidity, obstruction, dyspnea, and
      previous severe exacerbations) index can accurately predict mortality, hospital
      readmission, and their combination for the period from 3 months to 1 year after
      discharge in patients hospitalized for COPD. METHODS: A multicenter study of
      patients hospitalized for COPD exacerbations was used to develop the CODEX index,
      and a different patient cohort was used for validation. Comorbidity was measured
      using the age-adjusted Charlson index, whereas dyspnea, obstruction, and severe
      exacerbations were calculated according to BODEX (BMI, airfl ow obstruction,
      dyspnea, and previous severe exacerbations) thresholds. Information about
      mortality and readmissions for COPD or other causes was collected at 3 and 12
      months after hospital discharge. RESULTS: Two sets of 606 and 377 patients were
      included in the development and validation cohorts, respectively. The CODEX index
      was associated with mortality at 3 months ( P < .0001; hazard ratio [HR], 1.5;
      95% CI, 1.2-1.8) and 1 year ( P < .0001; HR, 1.3; 95% CI, 1.2-1.5 ), hospital
      readmissions in the same periods, and their combination (all P < .0001). All
      CODEX C statistics were superior to those of the BODEX, DOSE (dyspnea, airfl ow
      obstruction, smoking status, and exacerbation frequency), and updated ADO (age,
      dyspnea, and airfl ow obstruction) indexes. CONCLUSIONS: The CODEX index was a
      useful predictor of survival and readmission at both 3 months and 1 year after
      hospital discharge for a COPD exacerbation, with a prognostic capacity superior
      to other previously published indexes.

PMID- 24077343
TI  - Intestinal aGVHD and infection after hematopoietic stem cell transplantation.
AB  - BACKGROUND: We aimed to guide clinical nursing by studying the relationship
      between intestinal acute graft-versus-host disease and intestinal infection after
      hematopoietic stem cell transplantation. MATERIAL/METHODS: We present an
      effective nursing method by comparing and analyzing the degree, duration time,
      and volume of diarrhea, and the distribution of pathogens in 44 patients who
      developed intestinal aGVHD after hematopoietic stem cell transplantation (24
      patients with no intestinal infection). RESULTS: 21.4% of patients with grade I
      II intestinal aGVHD developed into intestinal infection and 87.5% of patients
      with grade III-IV intestinal aGVHD developed into intestinal infection (P<0.05).
      Higher mortality was found in the grade III-IV intestinal aGVHD patients with
      intestinal infection. Patient age had no effect on the incidence of GVHD
      according to our data (P<0.05). We found remarkable differences in the amount and
      duration of diarrhea between patients with and without intestinal infection
      (P<0.05). The most common pathogens cultivated were Candida glabrata (24%) and
      Candida albicans (22.67%). CONCLUSIONS: The incidence of intestinal infection
      increased remarkably after intestinal aGVHD occurred. Severe aGVHD can easily
      lead to fungus infection. Nursing care can decrease the incidence of intestinal
      infection in aGVHD.

PMID- 24077344
TI  - Rapid and quantitative one-pot synthesis of sequence-controlled polymers by
      radical polymerization.
AB  - A long-standing challenge in polymer chemistry has been to prepare synthetic
      polymers with not only well-defined molecular weight, but also precisely
      controlled microstructure in terms of the distribution of monomeric units along
      the chain. Here we describe a simple and scalable method that enables the
      synthesis of sequence-controlled multiblock copolymers with precisely defined
      high-order structures, covering a wide range of functional groups. We develop a
      one-pot, multistep sequential polymerization process with yields >99%, giving
      access to a wide range of such multifunctional multiblock copolymers. To
      illustrate the enormous potential of this approach, we describe the synthesis of
      a dodecablock copolymer, a functional hexablock copolymer and an icosablock (20
      blocks) copolymer, which represents the largest number of blocks seen to date,
      all of very narrow molecular weight distribution for such complex structures. We
      believe this approach paves the way to the design and synthesis of a new
      generation of synthetic polymers.

PMID- 24077345
TI  - Formaldehyde induces toxic effects and regulates the expression of damage
      response genes in BM-MSCs.
AB  - In this study, we assessed the toxic effects of formaldehyde (FA) on mouse bone
      marrow mesenchymal stem cells (BM-MSCs). Cytotoxicity was measured by using MTT
      assay. DNA strand breakage was detected by standard alkaline comet assay and
      comet assay modified with proteinase K (PK). DNA-protein crosslinks (DPCs) were
      detected by KCl-SDS precipitation assay. We found that FA at a concentration from
      75 to 200 MUM inhibited cell survival and induced DPCs over 125 MUM. The PK
      modified comet assay showed that FA-induced DNA strand breakage was increased in
      a dose-dependent manner from 75 to 200 MUM. On the other hand, standard alkaline
      comet assay showed that DNA strand breakage was decreased with FA concentration
      over 125 MUM. We confirmed by using Pearson correlation that there was a negative
      linear correlation between DPCs and survival rate (r = -0.987, P < 0.01) and
      positive linear relationships between DPCs and (i) sister chromatid exchange and
      (ii) micronucleus (r = 0.995, P < 0.01; r = 0.968, P < 0.01). DNA damage RT(2)
      profiler polymerase chain reaction array was used to investigate the changes in
      the expression of damage response genes. Xpa and Xpc of the nucleotide excision
      repair pathway and Brca2, Rad51, and Xrcc2 of the homologous recombination
      pathway were all up-regulated in both 75 and 125 MUM FA. However, the same genes
      were down-regulated with 175 MUM FA. The expressions of Chek1 and Hus1, which are
      involved in cell cycle regulation, were altered in the same manner with 75, 125,
      and 175 MUM FA. These results indicated that Xpa, Xpc, Brca2, Rad51, Xrcc2,
      Chek1, and Hus1 were essential for the BM-MSCs to counteract the effects of FA. 

PMID- 24077346
TI  - PI3K pathway activation provides a novel therapeutic target for pediatric
      ependymoma and is an independent marker of progression-free survival.
AB  - PURPOSE: Currently, there are few effective adjuvant therapies for pediatric
      ependymoma outside confocal radiation, and prognosis remains poor. The
      phosphoinositide 3-kinase (PI3K) pathway is one of the most commonly activated
      pathways in cancer. PI3Ks transduce signals from growth factors and cytokines,
      resulting in the phosphorylation and activation of AKT, which in turn induces
      changes in cell growth, proliferation, and apoptosis. EXPERIMENTAL DESIGN: PI3K
      pathway status was analyzed in ependymoma using gene expression data and
      immunohistochemical analysis of phosphorylated AKT (P-AKT). The effect of the
      PI3K pathway on cell proliferation was investigated by immunohistochemical
      analysis of cyclin D1 and Ki67, plus in vitro functional analysis. To identify a
      potential mechanism of PI3K pathway activation, PTEN protein expression and the
      mutation status of PI3K catalytic subunit alpha-isoform gene (PIK3CA) was
      investigated. RESULTS: Genes in the pathway displayed significantly higher
      expression in supratentorial than in posterior fossa and spinal ependymomas. P
      AKT protein expression, indicating pathway activation, was seen in 72% of tumors
      (n = 169) and P-AKT expression was found to be an independent marker of a poorer
      progression-free survival. A significant association between PI3K pathway
      activation and cell proliferation was identified, suggesting that pathway
      activation was influencing this process. PTEN protein loss was not associated
      with P-AKT staining and no mutations were identified in PIK3CA. CONCLUSIONS: Our
      results suggest that the PI3K pathway could act as a biomarker, not only
      identifying patients with a worse prognosis but also those that could be treated
      with therapies targeted against the pathway, a strategy potentially effective in
      a high percentage of ependymoma patients.

PMID- 24077347
TI  - Associations between single-nucleotide polymorphisms in the PI3K-PTEN-AKT-mTOR
      pathway and increased risk of brain metastasis in patients with non-small cell
      lung cancer.
AB  - PURPOSE: Non-small cell lung cancer (NSCLC) metastasizes fairly often to the
      brain, but identifying which patients will develop brain metastases is
      problematic. The phosphoinositide 3-kinase (PI3K)-AKT-mTOR signaling pathway is
      important in the control of cell growth, tumorigenesis, and cell invasion. We
      hypothesized that genotype variants in this pathway could predict brain
      metastasis in patients with NSCLC. METHODS: We genotyped 16 single-nucleotide
      polymorphisms (SNP) in five core genes (PIK3CA, PTEN, AKT1, AKT2, and FRAP1) by
      using DNA from blood samples of 317 patients with NSCLC, and evaluated potential
      associations with the subsequent development of brain metastasis, the cumulative
      incidence of which was estimated with Kaplan-Meier analysis. Multivariate Cox
      regression analysis was used to analyze correlations between genotype variants
      and the occurrence of brain metastasis. RESULTS: In analysis of individual SNPs,
      the GT/GG genotype of AKT1: rs2498804, CT/TT genotype of AKT1: rs2494732, and
      AG/AA genotype of PIK3CA: rs2699887 were associated with higher risk of brain
      metastasis at 24-month follow-up [respective HRs, 1.860, 95% confidence interval
      (CI) 1.199-2.885, P = 0.006; HR 1.902, 95% CI 1.259-2.875, P = 0.002; and HR
      1.933, 95% CI 1.168-3.200, P = 0.010]. We further found that these SNPs had a
      cumulative effect on brain metastasis risk, with that risk being highest for
      patients carrying both of these unfavorable genotypes (P = 0.003). CONCLUSIONS:
      Confirmation of our findings, the first to indicate that genetic variations in
      PI3K-AKT-mTOR can predict brain metastasis, in prospective studies would
      facilitate stratification of patients for brain metastasis prevention trials.

PMID- 24077348
TI  - JMJD2B promotes epithelial-mesenchymal transition by cooperating with beta
      catenin and enhances gastric cancer metastasis.
AB  - PURPOSE: This study investigated the role of histone demethylase Jumonji domain
      containing protein 2B (JMJD2B) in promoting epithelial-mesenchymal transition
      (EMT) and underlying molecular mechanisms in the progression of gastric cancer.
      EXPERIMENTAL DESIGN: The induction of EMT by JMJD2B in gastric cancer cells and
      its underlying mechanisms were examined by a series of assays. In vivo and in
      vitro assays were performed to clarify invasive potential of JMJD2B in gastric
      cancer cells. The expression dynamics of JMJD2B were detected using
      immunohistochemistry in 101 cases of primary gastric cancer tissues. RESULTS:
      Inhibition of JMJD2B by specific siRNA suppresses EMT of gastric cancer cells,
      whereas ectopic expression of JMJD2B induces EMT. Importantly, JMJD2B is
      physically associated with beta-catenin and enhances its nuclear localization and
      transcriptional activity. JMJD2B, together with beta-catenin, binds to the
      promoter of the beta-catenin target gene vimentin to increase its transcription
      by inducing H3K9 demethylation locally. JMJD2B inhibition attenuates migration
      and invasion of gastric cancer cells in vitro and metastasis in vivo. The
      expression of JMJD2B was positively correlated with tumor size (P = 0.017),
      differentiation status (P = 0.002), tumor invasion (P = 0.045), lymph node
      metastasis (P = 0.000), distant metastasis (P = 0.024), and tumor-node-metastasis
      (TNM) stage (P = 0.002) in patients with gastric cancer. CONCLUSIONS: The data
      reveal a novel function of JMJD2B in promoting EMT and gastric cancer invasion
      and metastasis, implicating JMJD2B as a potential target for reversing EMT and
      intervention of the progression of gastric cancer.

PMID- 24077349
TI  - Promoter hypomethylation of EpCAM-regulated bone morphogenetic protein gene
      family in recurrent endometrial cancer.
AB  - PURPOSE: Epigenetic regulation by promoter methylation plays a key role in
      tumorigenesis. Our goal was to investigate whether altered DNA methylation
      signatures associated with oncogenic signaling delineate biomarkers predictive of
      endometrial cancer recurrence. EXPERIMENTAL DESIGN: Methyl-CpG-capture sequencing
      was used for global screening of aberrant DNA methylation in our endometrial
      cancer cohort, followed by validation in an independent The Cancer Genome Atlas
      (TCGA) cohort. Bioinformatics as well as functional analyses in vitro, using RNA
      interference (RNAi) knockdown, were performed to examine regulatory mechanisms of
      candidate gene expression and contribution to aggressive phenotype, such as
      epithelial-mesenchymal transition (EMT). RESULTS: We identified 2,302
      hypermethylated loci in endometrial tumors compared with control samples. Bone
      morphogenetic protein (BMP) family genes, including BMP1, 2, 3, 4, and 7, were
      among the frequently hypermethylated loci. Interestingly, BMP2, 3, 4, and 7 were
      less methylated in primary tumors with subsequent recurrence and in patients with
      shorter disease-free interval compared with nonrecurrent tumors, which was
      validated and associated with poor survival in the TCGA cohort (BMP4, P = 0.009;
      BMP7, P = 0.007). Stimulation of endometrial cancer cells with epidermal growth
      factor (EGF) induced EMT and transcriptional activation of these genes, which was
      mediated by the epithelial cell adhesion molecule (EpCAM). EGF signaling was
      implicated in maintaining the promoters of candidate BMP genes in an active
      chromatin configuration and thus subject to transcriptional activation.
      CONCLUSIONS: Hypomethylation signatures of candidate BMP genes associated with
      EpCAM-mediated expression present putative biomarkers predictive of poor survival
      in endometrial cancer.

PMID- 24077350
TI  - Proteomic markers of DNA repair and PI3K pathway activation predict response to
      the PARP inhibitor BMN 673 in small cell lung cancer.
AB  - PURPOSE: Small cell lung carcinoma (SCLC) is an aggressive malignancy affecting
      nearly 30,000 people annually in the United States. We have previously identified
      elevated PARP1 levels in SCLC and demonstrated in vitro sensitivity to the PARP
      inhibitors AZD 2281 and AG014699. Here, we evaluate activity of a novel, potent
      PARP inhibitor, BMN 673, and identify markers of response as a basis for
      developing predictive markers for clinical application. EXPERIMENTAL DESIGN:
      Inhibition of SCLC proliferation by BMN 673 was assayed in vitro and effects on
      tumor growth were measured in SCLC xenograft models. Protein expression and
      pathway activation was assessed by reverse phase protein array and western blot
      analysis. PARP inhibition was confirmed using a PAR ELISA. RESULTS: We
      demonstrate striking, single agent activity of BMN 673 in SCLC cell lines and
      xenografts, with single agent BMN 673 exhibiting in vivo activity similar to
      cisplatin. Sensitivity to BMN 673 was associated with elevated baseline
      expression levels of several DNA repair proteins, whereas greater drug resistance
      was observed in SCLC models with baseline activation of the PI3K/mTOR pathway.
      Furthermore, we developed and confirmed these data with a novel "DNA repair
      score" consisting of a group of 17 DNA repair proteins. CONCLUSIONS: Elevated
      expression of multiple DNA repair proteins, as well as a corresponding "DNA
      repair protein score," predict response to BMN 673 in in vitro SCLC models. These
      observations complement recent work in which PI3K inhibition sensitizes breast
      cancer models to PARP inhibition, suggesting cooperation between DNA repair and
      PI3K pathways.

PMID- 24077351
TI  - Phase I study of vismodegib in children with recurrent or refractory
      medulloblastoma: a pediatric brain tumor consortium study.
AB  - PURPOSE: To investigate the safety, dose-limiting toxicities, and
      pharmacokinetics of the smoothened inhibitor vismodegib in children with
      refractory or relapsed medulloblastoma. EXPERIMENTAL DESIGN: Initially,
      vismodegib was administered daily at 85 mg/m(2) and escalated to 170 mg/m(2). The
      study was then revised to investigate a flat-dosing schedule of 150 mg for
      patients with small body surface area (BSA, 0.67-1.32 m(2)) or 300 mg for those
      who were larger (BSA, 1.33-2.20 m(2)). Pharmacokinetics were performed during the
      first course of therapy, and the right knees of all patients were imaged to
      monitor bone toxicity. Immunohistochemical analysis was done to identify patients
      with Sonic Hedgehog (SHH)-subtype medulloblastoma. RESULTS: Thirteen eligible
      patients were enrolled in the initial study: 6 received 85 mg/m(2) vismodegib,
      and 7 received 170 mg/m(2). Twenty eligible patients were enrolled in the flat
      dosing part of the study: 10 at each dosage level. Three dose-limiting toxicities
      were observed, but no drug-related bone toxicity was documented. The median
      (range) vismodegib penetration in the cerebrospinal fluid (CSF) was 0.53 (0.26
      0.78), when expressed as a ratio of the concentration of vismodegib in the CSF to
      that of the unbound drug in plasma. Antitumor activity was seen in 1 of 3
      patients with SHH-subtype disease whose tumors were evaluable, and in none of the
      patients in the other subgroups. CONCLUSIONS: Vismodegib was well tolerated in
      children with recurrent or refractory medulloblastoma; only two dose-limiting
      toxicities were observed with flat dosing. The recommended phase II study dose is
      150 or 300 mg, depending on the patient's BSA. Clin Cancer Res; 19(22); 6305-12.
      (c)2013 AACR.

PMID- 24077354
TI  - Analysis of metaplastic breast carcinoma: FNAC; histopathology and
      immunohistochemistry are complementary for diagnosis.
AB  - BACKGROUND: Metaplastic breast carcinoma (MBC) is a rare malignancy comprised of
      ductal, squamous and/or mesenchymal elements with problematic diagnosis.
      OBJECTIVE: This study analyses MBC identifying its cytologic and histologic
      features and emphasizing the combined role of FNAC, histopathology and
      immunohistochemistry (IHC) in its diagnosis. MATERIALS AND METHODS: Cytology and
      histopathology files search yielded 21 cases identified as MBC from January 2005
      to December 2010. FNAC and the histopathology slides were re-examined for the
      presence and frequency of various elements. Cytological and histopathological
      diagnoses were made and the cases subtyped according to WHO classification.
      Cytokeratin and vimenten IHC were used to confirm diagnosis when required.
      RESULTS: On FNAC, 52.4% were diagnosed as malignant, 9.5% as suspicious for
      malignancy and 38.1% as benign lesions. Most frequent cytologic findings were
      squamous and spindle cell elements (52.4% each). Histopathology revealed 76.2%
      pure epithelial tumors and 23.8% mixed epithelial-mesenchymal tumors. Squamous
      cell carcinoma was the most frequent histological subtype (33.3%).
      Carcinosarcomas were dimorphic on IHC& spindle cell carcinomas were positive for
      both cytokeratin and vimentin. CONCLUSION: Presence of dual components, squamous,
      spindle elements, mesenchymal fragments and necrosis in moderate to high
      cellularity breast FNAC provides clues for the diagnosis of MBC. FNAC;
      histopathology and IHC complement for diagnosis.

PMID- 24077353
TI  - New strategies in radiation therapy: exploiting the full potential of protons.
AB  - Protons provide significant dosimetric advantages compared with photons because
      of their unique depth-dose distribution characteristics. However, they are more
      sensitive to the effects of intra- and intertreatment fraction anatomic
      variations and uncertainties in treatment setup. Furthermore, in the current
      practice of proton therapy, the biologic effectiveness of protons relative to
      photons is assumed to have a generic fixed value of 1.1. However, this is a
      simplification, and it is likely higher in different portions of the proton beam.
      Current clinical practice and trials have not fully exploited the unique physical
      and biologic properties of protons. Intensity-modulated proton therapy, with its
      ability to manipulate energies (in addition to intensities), provides an entirely
      new dimension, which, with ongoing research, has considerable potential to
      increase the therapeutic ratio.

PMID- 24077352
TI  - Molecular chaperone gp96 is a novel therapeutic target of multiple myeloma.
AB  - PURPOSE: gp96 (grp94) is a key downstream chaperone in the endoplasmic reticulum
      (ER) to mediate unfolded protein response (UPR) and the pathogenesis of multiple
      myeloma is closely linked to dysregulated UPR. In this study, we aimed to
      determine the roles of gp96 in the initiation and progression of multiple myeloma
      in vivo and in vitro. EXPERIMENTAL DESIGN: We generated a mouse model with
      overexpression of XBP1s and conditional deletion of gp96 in B-cell compartment
      simultaneously to identify the roles of gp96 in the development of multiple
      myeloma in vivo. Using a short hairpin RNA (shRNA) system, we silenced gp96 in
      multiple human multiple myeloma cells and examined the effect of gp96 knockdown
      on multiple myeloma cells by cell proliferation, cell-cycle analysis, apoptosis
      assay, immunohistochemistry, and human myeloma xenograft model. The anticancer
      activity of gp96 selective inhibitor, WS13, was evaluated by apoptosis assay and
      MTT assay. RESULTS: Genetic deletion of gp96 in XBP1s-Tg mice attenuates multiple
      myeloma. Silencing of gp96 causes severe compromise in human multiple myeloma
      cell growth through inhibiting Wnt-LRP-survivin pathway. We also confirmed that
      knockdown of gp96 decreased human multiple myeloma growth in a murine xenograft
      model. The targeted gp96 inhibitor induced apoptosis and blocked multiple myeloma
      cell growth, but did not induce apoptosis in pre-B leukemic cells. We have
      demonstrated that myeloma growth is dependent on gp96 both genetically and
      pharmacologically. CONCLUSIONS: gp96 is essential for multiple myeloma cell
      proliferation and survival, suggesting that gp96 is a novel therapeutic target
      for multiple myeloma. Clin Cancer Res; 19(22); 6242-51. (c)2013 AACR.

PMID- 24077355
TI  - First-principle calculations on the structural stability and electronic
      properties of superhard BxCy compounds.
AB  - With first-principle calculations, we studied the structural stability and
      electronic properties of the BxCy compounds based on three kinds of phases
      including diamond-like, C20-like and B15-like phases. The C20-like structure
      B8C12 is found to be a new stable structure with relatively low formation energy
      in middle boron concentration and is expected to be synthesized experimentally.
      Combined with a microscopic model, the Vickers hardness of the different
      configurations of BxCy compounds is analyzed with the change of boron
      concentration. It is found that the hardness of the B-C system has a decreasing
      trend with the increase of boron concentration. In addition, all the structures
      have metallic properties, except B12C3 and B14C. With the analysis of Mulliken
      bond population and charge distribution, the bonds with high electron density and
      short bond length have an important contribution to the hardness in the B-C
      system, while the effect of metallicity to hardness can be ignored.

PMID- 24077356
TI  - Development and validation of a lifetime exposure questionnaire for use among
      Chinese populations.
AB  - The sunlight exposure questionnaire for use in the Chinese population was
      constructed based on extensive literature review and item suitability for
      measuring life-time exposure. The content validity index (CVI) was derived from
      ratings by, an expert panel to assess the item content and relevance. 650
      population-based Chinese women completed the sunlight exposure questionnaire
      through telephone interview. To assess the questionnaire reliability, 94 women
      were re-interviewed after 2 weeks. 98.4% of the sunlight exposure questionnaire
      items were found to have valid CVI (>0.83). The Scree plot and the Principal
      Components Factor Analysis showed a two-factor construct was appropriate and no
      questionnaire item needed to be excluded. The questionnaire also had a good test
      retest reliability (ICC: 0.59-0.93; k: 0.51-100). This sunlight exposure
      questionnaire was found to be adequate for measurement of life-time sunlight
      exposure among Hong Kong Chinese women. 

PMID- 24077357
TI  - Synthesis and anti-angiogenetic activity evaluation of N-(3-aryl
      acryloyl)aminosaccharide derivatives.
AB  - In order to find novel potent inhibitors for signal pathways of FGF/FGFR,
      nineteen N-(3-aryl acryloyl)aminosaccharide derivatives were designed and
      synthesized based on the binding sites of FGF and oligosaccharides of heparin.
      Their structures were confirmed by IR, (1)H NMR, (13)C NMR, MS and elemental
      analysis. The nineteen target compounds were evaluated for biological activity
      against HUVEC cell. In vitro assays showed that compound 10s (IC50=5.3MUM)
      exhibited comparable inhibitory effects on endothelial cell growth with topotecan
      (IC50=2.7MUM). Compound 10s (10MUg/egg) also showed obvious anti-angiogenetic
      activity in the in vivo chicken chorio allantoic membrane (CAM) assay, and the
      potency was similar to topotecan (10MUg/egg). 

PMID- 24077358
TI  - A 68-year-old phenotypically male patient with 21-hydroxylase deficiency and
      concomitant adrenocortical neoplasm producing testosterone and cortisol.
AB  - The steroidogenic enzyme 21-hydroxylase is necessary for the synthesis of both
      glucocorticoids and mineralocorticoids. 21-hydroxylase is a cytochrome P-450
      enzyme and is encoded by the gene CYP21A2. Here we report a 68-year-old
      phenotypically 'male' but genetically female patient with 21-hydroxylase
      deficiency (21OHD) and the concomitant virilizing adrenocortical carcinoma. This
      patient grew up as a male and has not encountered any episodes of adrenal
      insufficiency without glucocorticoid replacement in his lifetime. A chromosome
      test at admission, however, identified the 46, XX karyotype, and serum 17
      hydroxyprogesterone and urine pregnanetriolone and 11beta-hydroxyandrostendione
      were all elevated, consistent with 21OHD. Moreover, serum testosterone was 1.90
      ng/ml, much higher than the female standard levels, and serum cortisol was 5.7
      ug/ml, slightly lower than standard levels. Genetic analysis identified the
      patient as a heterozygote of the two pathogenic mutations in the CYP21A2 gene:
      IVS2-13C(A)>G and R356W. Magnetic resonance imaging (MRI) revealed the presence
      of left adrenal tumor measuring 6 cm, which was subsequently diagnosed as
      adrenocortical carcinoma based on the criteria of Weiss. Immunohistochemical
      analysis of the tumor specimens revealed the expression of various enzymes
      involved in testosterone production, including 3beta-hydroxysteroid
      dehydrogenase, 17alpha-hydroxylase/17,20-lyase, and 17beta-hydroxysteroid
      dehydrogenase. Importantly, the expression of immunoreactive 21-hydroxylase was
      detected in these tumor cells. The levels of adrenal tumor-derived steroid
      metabolites were all markedly decreased following the surgery. This is the first
      report on a virilized 21OHD patient associated with the adrenocortical tumor that
      produces testosterone. Moreover, the concomitant adrenocortical tumor may
      ameliorate adrenocortical insufficiency by producing cortisol. 

PMID- 24077359
TI  - Impact of fluid-rock chemical interactions on tracer transport in fractured
      rocks.
AB  - In this paper, we investigate the impact of chemical interactions, in the form of
      mineral precipitation and dissolution reactions, on tracer transport in fractured
      rocks. When a tracer is introduced in fractured rocks, it moves through the
      fracture primarily by advection and it also enters the stagnant water of the
      surrounding rock matrix through diffusion. Inside the porous rock matrix, the
      tracer chemically interacts with the solid materials of the rock, where it can
      precipitate depending on the local equilibrium conditions. Alternatively, it can
      be dissolved from the solid phase of the rock matrix into the matrix pore water,
      diffuse into the flowing fluids of the fracture and is advected out of it. We
      show that such chemical interactions between the fluid and solid phases have
      significant impact on tracer transport in fractured rocks. We invoke the dual
      porosity conceptualization to represent the fractured rocks and develop a semi
      analytical solution to describe the transient transport of tracers in interacting
      fluid-rock systems. To test the accuracy and stability of the semi-analytical
      solution, we compare it with simulation results obtained with the TOUGHREACT
      simulator. We observe that, in a chemically interacting system, the tracer
      breakthrough curve exhibits a pseudo-steady state, where the tracer concentration
      remains more or less constant over a finite period of time. Such a pseudo-steady
      condition is not observed in a non-reactive fluid-rock system. We show that the
      duration of the pseudo-state depends on the physical and chemical parameters of
      the system, and can be exploited to extract information about the fractured rock
      system, such as the fracture spacing and fracture-matrix interface area. 

PMID- 24077360
TI  - Hybrid ternary rice paper-manganese oxide-carbon nanotube nanocomposites for
      flexible supercapacitors.
AB  - Modern portable electronic devices create a strong demand for flexible energy
      storage devices. Paper based nanocomposites are attractive as sustainable
      materials for such applications. Here, we directly explored the hydroxyl
      chemistry of cellulose fibers to synthesize hybrid ternary nanocomposites,
      comprised of rice paper, single-walled carbon nanotubes (SWCNTs) and manganese
      oxide nanoparticles. The functional groups on cellulose fibers can react with
      adsorbed permanganate ions, resulting in uniform deposition of manganese oxide
      nanoparticles. SWCNTs coated on top of manganese oxide nanoparticles form a
      highly conductive network connecting individual manganese oxide particles. By
      using the hybrid ternary composites as electrodes, the assembled two-electrode
      supercapacitors demonstrated high capacitance (260.2 F g(-1)), energy (9.0 W h
      kg(-1)), power (59.7 kW kg(-1)), and cycle stability (12% drop after 3000
      cycles). In addition, the nanocomposites show good strength and excellent
      mechanical flexibility, and their capacitance shows negligible changes after
      bending more than 100 times. These findings suggest that opportunities exist to
      further explore the rich chemistry of cellulose fibers for innovative energy
      applications. 

PMID- 24077361
TI  - Engineering metal-based luminescence in coordination polymers and metal-organic
      frameworks.
AB  - The rapidly growing number of luminescent coordination polymers (CPs) and metal
      organic frameworks (MOFs) illustrates high interest as well as accessibility of
      such materials. The interplay between inorganic and organic components in these
      materials offers a large number of viable luminescence processes. The enormous
      variability of available ligand-metal combinations opens the possibility of
      creating luminescence "by design", based on a proper understanding of the
      processes involved. Together with the multifunctionality of MOFs (e.g. porosity)
      further options like sensing become accessible. This tutorial review covers the
      main luminescence processes and focuses especially on metal-based luminescence of
      coordination polymers and MOFs. 

PMID- 24077362
TI  - Construction and Evaluation of a Prototype High Resolution, Silicon
      Photomultiplier-Based, Tandem Positron Emission Tomography System.
AB  - While the performance of most current commercially available PET scanners is
      sufficient for many standard clinical applications, some specific tasks likely
      require specialized imaging systems. The goal of this project is to explore the
      capabilities and limitations of a small, high-resolution prototype system for
      obtaining PET images. The scanner consists of a tandem of detectors. One is a
      small detector consisting of a 20 * 20 array of 0.7 * 0.7 * 3 mm3 (pitch 0.8 mm)
      LYSO elements. The scintillator array is coupled to an array of silicon
      photomultipliers. The second detector is a 96 * 72 array of 2 * 2 * 15 mm3 (pitch
      = 2.1 mm) LYSO elements coupled to PSPMTs. Separation between the two devices is
      180 mm. The detectors are operated in coincidence with each other. Image
      reconstruction is performed using a limited angle, Maximum Likelihood Expectation
      Maximization (MLEM) algorithm. Evaluation of the device included measurements of
      spatial resolution and detection sensitivity as a function of distance. The
      transaxial radial and tangential spatial resolution of the system ranged from 0.6
      mm to 0.9 mm FWHM; axial resolution ranged from 2.7 mm to 4.6 mm FWHM. Detection
      sensitivity ranged from 0.05 to 0.28%. Spatial resolution and field-of-view vary
      as a function of distance from the small detector. The tandem detector insert
      permitted differentiation of the smallest (1 mm diameter) rods in a mini-hot rod
      phantom. The results indicate that a tandem PET imaging scheme can be potentially
      employed in applications where high-resolution images over a small region are
      required.

PMID- 24077363
TI  - Integration of Administrative Data and Chart Review for Reporting Health Care
      Utilization Among Children With Sickle Cell Disease.
AB  - Health care utilization of children with sickle cell disease (SCD) has been well
      documented due to an increase in the use of administrative data sets. While use
      of such data sources is relatively efficient and low cost, questions remain as to
      whether they provide sufficient information to fully characterize health care
      use. The aim of this study was to determine whether administrative data have the
      capacity to fully assess health care utilization among children with SCD. We
      studied the health care utilization of 154 low-income children with SCD in a
      managed care organization combining administrative data and medical record
      review. In our comparison, we found that administrative claims provided key
      information on the scope and location of health service use and that sole
      reliance on medical record review may undercount unique members and encounters.

PMID- 24077365
TI  - VP1 B-C and D-E loops of bovine enterovirus cluster B can effectively display
      foot-and-mouth disease virus type O-conserved neutralizing epitope.
AB  - On the basis of generation of an infectious cDNA clone for the BHM26 strain of
      bovine enterovirus cluster B (BEV-B), 22 sites on different loops of the BHM26
      capsid were selected according to an alignment of its sequence with the
      structural motifs of BEV-A strain VG-5-27 for insertion of the foot-and-mouth
      disease virus (FMDV) type O-conserved neutralizing epitope 8E8. Two recombinant
      viruses, rBEV-A1 and rBEV-DE, in which the FMDV epitope was inserted into the VP1
      B-C or D-E loops, were rescued by transfection of BHK-21 cells with the in vitro
      transcribed RNA of the recombinant BHM26 genome-length cDNA constructs. The two
      epitope-inserted viruses were genetically stable and exhibited growth properties
      similar to those of their parental virus in BHK-21 and IBRS-2 cells, which are
      susceptible to both BEV and FMDV. However, the two recombinant BEVs (rBEVs) had a
      significantly lower growth titre than those of the parental virus BHM26 in MDBK
      and Marc145 cells, which are susceptible to BEV but not to FMDV. These results
      indicated that insertion of the FMDV epitope into the VP1 B-C or D-E loops of the
      BEV particle altered the replication properties of BEV. In addition, the two
      rBEVs were sensitive to neutralization by the FMDV type O-specific mAb 8E8, and
      anti-FMDV IgG antibodies were induced in mice by intramuscular inoculation with
      the rBEV-A1 and rBEV-DE viruses. Our results demonstrate that the VP1 B-C and D-E
      loops of the BEV-B particle can effectively display a foreign epitope, making
      this an attractive approach for the design of BEV-vectored and epitope-based
      vaccines. 

PMID- 24077364
TI  - Deep sequencing identifies two genotypes and high viral genetic diversity of
      human pegivirus (GB virus C) in rural Ugandan patients.
AB  - Human pegivirus (HPgV), formerly 'GB virus C' or 'hepatitis G virus', is a member
      of the genus Flavivirus (Flaviviridae) that has garnered significant attention
      due to its inhibition of HIV, including slowing disease progression and
      prolonging survival in HIV-infected patients. Currently, there are six proposed
      HPgV genotypes that have roughly distinct geographical distributions. Genotypes 2
      and 3 are the most comprehensively characterized, whereas those genotypes
      occurring on the African continent, where HPgV prevalence is highest, are less
      well studied. Using deep sequencing methods, we identified complete coding HPgV
      sequences in four of 28 patients (14.3%) in rural Uganda, east Africa. One of
      these sequences corresponds to genotype 1 and is the first complete genome of
      this genotype from east Africa. The remaining three sequences correspond to
      genotype 5, a genotype that was previously considered exclusively South African.
      All four positive samples were collected within a geographical area of less than
      25 km(2), showing that multiple HPgV genotypes co-circulate in this area.
      Analysis of intra-host viral genetic diversity revealed that total single
      nucleotide polymorphism frequency was approximately tenfold lower in HPgV than in
      hepatitis C virus. Finally, one patient was co-infected with HPgV and HIV, which,
      in combination with the high prevalence of HIV, suggests that this region would
      be a useful locale to study the interactions and co-evolution of these viruses.

PMID- 24077366
TI  - Delayed induction of proinflammatory cytokines and suppression of innate
      antiviral response by the novel Middle East respiratory syndrome coronavirus:
      implications for pathogenesis and treatment.
AB  - The high mortality associated with the novel Middle East respiratory syndrome
      coronavirus (MERS-CoV) has raised questions about the possible role of a cytokine
      storm in its pathogenesis. Although recent studies showed that MERS-CoV infection
      is associated with an attenuated IFN response, no induction of inflammatory
      cytokines was demonstrated during the early phase of infection. To study both
      early and late cytokine responses associated with MERS-CoV infection, we measured
      the mRNA levels of eight cytokine genes [TNF-alpha, IL-1beta, IL-6, IL-8, IFN
      beta, monocyte chemotactic protein-1, transforming growth factor-beta and IFN
      gamma-induced protein (IP)-10] in cell lysates of polarized airway epithelial
      Calu-3 cells infected with MERS-CoV or severe acute respiratory syndrome (SARS)
      CoV up to 30 h post-infection. Among the eight cytokine genes, IL-1beta, IL-6 and
      IL-8 induced by MERS-CoV were markedly higher than those induced by SARS-CoV at
      30 h, whilst TNF-alpha, IFN-beta and IP-10 induced by SARS-CoV were markedly
      higher than those induced by MERS-CoV at 24 and 30 h in infected Calu-3 cells.
      The activation of IL-8 and attenuated IFN-beta response by MERS-CoV were also
      confirmed by protein measurements in the culture supernatant when compared with
      SARS-CoV and Sendai virus. To further confirm the attenuated antiviral response,
      cytokine response was compared with human HCoV-229E in embryonal lung fibroblast
      HFL cells, which also revealed higher IFN-beta and IP-10 levels induced by HCoV
      229E than MERS-CoV at 24 and 30 h. Whilst our data supported recent findings that
      MERS-CoV elicits attenuated innate immunity, this represents the first report to
      demonstrate delayed proinflammatory cytokine induction by MERS-CoV. Our results
      provide insights into the pathogenesis and treatment of MERS-CoV infections. 

PMID- 24077367
TI  - Antigenicity and transmissibility of a novel clade 2.3.2.1 avian influenza H5N1
      virus.
AB  - A genetic variant of the H5N1 influenza virus, termed subclade 2.3.2.1, was first
      identified in Bulgaria in 2010 and has subsequently been found in Vietnam and
      Laos. Several cases of human infections with this virus have been identified.
      Thus, it is important to understand the antigenic properties and transmissibility
      of this variant. Our results showed that, although it is phylogenetically closely
      related to other previously characterized clade 2.3 viruses, this novel 2.3.2.1
      variant exhibited distinct antigenic properties and showed little cross
      reactivity to sera raised against other H5N1 viruses. Like other H5N1 viruses,
      this variant bound preferentially to avian-type receptors, but contained
      substitutions at positions 190 and 158 of the haemagglutinin (HA) protein that
      have been postulated to facilitate HA binding to human-type receptors and to
      enhance viral transmissibility among mammals, respectively. However, this virus
      did not appear to have acquired the capacity for airborne transmission between
      ferrets. These findings highlight the challenges in selecting vaccine candidates
      for H5N1 influenza because these viruses continue to evolve rapidly in the field.
      It is important to note that some variants have obtained mutations that may gain
      transmissibility between model animals, and close surveillance of H5N1 viruses in
      poultry is warranted. 

PMID- 24077368
TI  - Publishing in Physical and rehabilitation medicine. An update on the European
      point of view.

PMID- 24077369
TI  - Total Bregman Divergence and its Applications to Shape Retrieval.
AB  - Shape database search is ubiquitous in the world of biometric systems, CAD
      systems etc. Shape data in these domains is experiencing an explosive growth and
      usually requires search of whole shape databases to retrieve the best matches
      with accuracy and efficiency for a variety of tasks. In this paper, we present a
      novel divergence measure between any two given points in [Formula: see text] or
      two distribution functions. This divergence measures the orthogonal distance
      between the tangent to the convex function (used in the definition of the
      divergence) at one of its input arguments and its second argument. This is in
      contrast to the ordinate distance taken in the usual definition of the Bregman
      class of divergences [4]. We use this orthogonal distance to redefine the Bregman
      class of divergences and develop a new theory for estimating the center of a set
      of vectors as well as probability distribution functions. The new class of
      divergences are dubbed the total Bregman divergence (TBD). We present the l1-norm
      based TBD center that is dubbed the t-center which is then used as a cluster
      center of a class of shapes The t-center is weighted mean and this weight is
      small for noise and outliers. We present a shape retrieval scheme using TBD and
      the t-center for representing the classes of shapes from the MPEG-7 database and
      compare the results with other state-of-the-art methods in literature.

PMID- 24077370
TI  - Effects of 18-week in-season heavy-resistance and power training on throwing
      velocity, strength, jumping, and maximal sprint swim performance of elite male
      water polo players.
AB  - We examined the effects of 18 weeks of strength and high-intensity training on
      key sport performance measures of elite male water polo (WP) players. Twenty
      seven players were randomly assigned to 2 groups, control (in-water training
      only) and strength group, (strength training sessions [twice per week] + in-water
      training). In-water training was conducted 5 d.wk. Twenty-meter maximal sprint
      swim, maximal dynamic strength 1-repetition maximum (1RM) for upper bench press
      (BP) and lower full squat (FS) body, countermovement jump (CMJ), and throwing
      velocity were measured before and after the training. The training program
      included upper and lower body strength and high-intensity exercises (BP, FS,
      military press, pull-ups, CMJ loaded, and abs). Baseline-training results showed
      no significant differences between the groups in any of the variables tested. No
      improvement was found in the control group; however, meaningful improvement was
      found in all variables in the experimental group: CMJ (2.38 cm, 6.9%, effect size
      [ES] = 0.48), BP (9.06 kg, 10.53%, ES = 0.66), FS (11.06 kg, 14.21%, ES = 0.67),
      throwing velocity (1.76 km.h(-1), 2.76%, ES = 0.25), and 20-m maximal sprint swim
      (-0.26 seconds, 2.25%, ES = 0.29). Specific strength and high-intensity training
      in male WP players for 18 weeks produced a positive effect on performance
      qualities highly specific to WP. Therefore, we propose modifications to the
      current training methodology for WP players to include strength and high
      intensity training for athlete preparation in this sport.

PMID- 24077371
TI  - The acute effect of mouth only breathing on time to completion, heart rate, rate
      of perceived exertion, blood lactate, and ventilatory measures during a high
      intensity shuttle run sequence.
AB  - This study investigated the effect of restricting nasal breathing during a series
      of 20-m shuttle runs. Ten male participants (mean age = 21.7 +/- 2.4 years,
      height = 1.80 +/- 0.62 m, mass = 79.2 +/- 10.4 kg, sum of 4 skinfolds = 54.5 +/-
      7.8 mm) were required to either (a) dive on the ground and complete a rolling
      sequence (condition = GRD) or (b) complete the shuttles while staying on their
      feet and tagging the line with 1 foot, at the end of each 20-m segment (condition
      = STD). The shuttle runs were completed with and without a nose clip (no clip =
      nc; with a clip = clip) under 4 different trial conditions in a randomized order
      (GRDnc; GRDclip; STDnc; and STDclip), requiring the participants to return on 4
      separate occasions separated by 5-7 days. Heart rate was recorded throughout each
      trial, and the rate of perceived exertion (RPE) was measured at the completion of
      each shuttle sequence. Pretrial and posttrial lactate and respiratory function
      measures were also recorded. The general linear model with repeated measures
      analysis indicated that there was a significant effect for Roll (GRD > STD) (p <=
      0.05) but not for Clip (p > 0.05) on total time to completion in the trials.
      There was no significant interaction of the conditions (Roll * Clip) for RPE (p >
      0.05). Similarly, there was no significant effect for blood lactate measured 3
      minutes post the last shuttle for Roll (p > 0.05) and Clip (p > 0.05). There was
      a significant main effect on the HR across all 6 time points (i.e., pre,
      intervals 1-4 and 10 minutes post) (p <= 0.05) and for Roll (GRD > STD) (p <=
      0.05), but not for Clip (p > 0.05). No significant effect of Roll or Clip was
      found for any of the recorded ventilation measures (p > 0.05). On the basis of
      these findings, the use of restricted nasal breathing, while performing a high
      intensity shuttle sequence as a method of increasing the acute training effect on
      athletes, is questionable, so strength and conditioning coaches should carefully
      consider their rationale for using such a training strategy.

PMID- 24077372
TI  - Effects of body fat and dominant somatotype on explosive strength and aerobic
      capacity trainability in prepubescent children.
AB  - The purpose of this study was to analyze the influence of body fat and somatotype
      on explosive strength and aerobic capacity trainability in the prepubertal growth
      spurt, marked by rapid changes in body size, shape, and composition, all of which
      are sexually dimorphic. One hundred twenty-five healthy children (58 boys, 67
      girls), aged 10-11 years (10.8 +/- 0.4 years), who were self-assessed in Tanner
      stages 1-2, were randomly assigned into 2 experimental groups to train twice a
      week for 8 weeks: strength training group (19 boys, 22 girls), endurance training
      group (21 boys, 24 girls), and a control group (18 boys, 21 girls). Evaluation of
      body fat was carried out using the method described by Slaughter. Somatotype was
      computed according to the Heath-Carter method. Increased endomorphy reduced the
      likelihood of vertical jump height improvement (odds ratio [OR], 0.10; 95%
      confidence interval [CI], 0.01-0.85), increased mesomorphy (OR, 6.15; 95% CI,
      1.52-24.88) and ectomorphy (OR, 6.52; 95% CI, 1.71-24.91) increased the
      likelihood of sprint performance, and increased ectomorphy (OR, 3.84; 95% CI,
      1.20-12.27) increased the likelihood of aerobic fitness gains. Sex did not affect
      the training-induced changes in strength or aerobic fitness. These data suggest
      that somatotype has an effect on explosive strength and aerobic capacity
      trainability, which should not be disregarded. The effect of adiposity on
      explosive strength, musculoskeletal magnitude on running speed, and relative
      linearity on running speed and aerobic capacity seem to be crucial factors
      related to training-induced gains in prepubescent boys and girls.

PMID- 24077373
TI  - Technical-tactical analysis of youth olympic taekwondo combat.
AB  - The purpose of this study was to define the technical and tactical profiles of
      official youth taekwondo competitions played under the most recent rules of the
      International Taekwondo Federation. Tactical actions (i.e., attack, defense, and
      block), technical executions (from 1- to 4-point scores), kicking legs (i.e.,
      front/rear and right/left), and overall technical effectiveness were investigated
      in relation to match outcome of semifinal and final competitions (n = 50) of
      youth (aged 13-14 years) black belt athletes during the Italian Taekwondo Cadet
      Championship. Differences (p < 0.001) were found among all action typologies
      (Attack: 50.9 +/- 2.2%; Defense: 27.7 +/- 1.5%; Block: 21.3 +/- 1.6%), with
      winners showing fewer (p = 0.005) offensive actions and more (p = 0.001)
      defensive actions with respect to non-winners. Independently from match outcome,
      technical exchanges showed differences (p < 0.001) for technical executions.
      Winners resulted more efficient (p < 0.001) for both technical and tactical
      variables. In general, these findings showed that Cadets tend to adopt an
      offensive strategy. In considering that the adoption of the new electronic system
      requires athletes to execute correct technical actions to have a score assigned,
      coaches should emphasize the effectiveness of scoring techniques and help
      athletes to effectively improve their defense and counterattack capabilities.

PMID- 24077374
TI  - Acute effect of constant torque and angle stretching on range of motion, muscle
      passive properties, and stretch discomfort perception.
AB  - The aim of the present study was to compare the acute effects of constant torque
      (CT) and constant angle (CA) stretching exercises on the maximum range of motion
      (ROMmax), passive stiffness (PS), and ROM corresponding to the first sensation of
      tightness in the posterior thigh (FSTROM). Twenty-three sedentary men (age, 19-33
      years) went through 1 familiarization session and afterward proceeded randomly to
      both CA and CT treatment stretching conditions, on separate days. An isokinetic
      dynamometer was used to analyze hamstring muscles during passive knee extension.
      The subjects performed 4 stretches of 30 seconds each with a 15-second interval
      between them. In the CA stretching, the subject reached a certain ROM (95% of
      ROMmax), and the angle was kept constant. However, in the CT stretching exercise,
      the volunteer reached a certain resistance torque (corresponding to 95% of
      ROMmax) and it was kept constant. The results showed an increase in ROMmax for
      both CA and CT (p < 0.001), but the increase was greater for CT than for CA (CA
      vs. CT in poststretching, p = 0.002). Although the PS decreased for both CA and
      CT (p < 0.001), the decrease was greater for CT than for CA (CA vs. CT in
      poststretching, p = 0.002). The FSTROM increased for both CA and CT, but the
      increase for CT was greater than that for CA (CA vs. CT in poststretching, p =
      0.003). The greater increase in ROMmax for the CT stretch may be explained by
      greater changes in the biomechanical properties of the muscle-tendon unit and
      stretch tolerance, as indicated by the results of PS and FSTROM.

PMID- 24077375
TI  - Six-Minute Walk Test Vs. Three-Minute Step Test for Measuring Functional
      Endurance.
AB  - The purpose of this study was to compare 2 practical measures of functional
      endurance. Specifically, the six-minute walk test (SMWT) and three-minute step
      test (TMST) were compared to determine their appropriateness for use as field
      tests and inclusion in the NIH Toolbox for the assessment of neurological and
      behavioral function. Individuals between 14 and 85 years performed both the SMWT
      and TMST in random order. We documented completion rates, criterion performance,
      heart rate responses, and subjective exertion associated with the 2 tests. All
      189 participants completed the SMWT, but only 73.0% completed the TMST. Those
      completing the TMST were more likely to be male, report better health, and have a
      younger age and lower body mass index. The SMWT distance was greater for those
      who did vs. those who did not complete the TMST. For those completing both tests,
      the average distance walked in 6 minutes was 595.9 m; the average cumulative
      heart beats during the minute after the TMST was 107.4. Distance walked and
      cumulative heart beats correlated weakly. Average heart rate and perceived
      exertion were significantly higher after the TMST than the SMWT. Posttest heart
      rate and perceived exertion for the 2 tests correlated significantly but not
      strongly. We conclude that the SMWT is more likely to be completed and is usually
      less stressful physiologically than the TMST and therefore may be a better option
      for field testing functional endurance and inclusion in the NIH Toolbox.

PMID- 24077376
TI  - Development and implementation of a novel measure for quantifying training loads
      in rowing: the T2minute method.
AB  - The systematic management of training requires accurate training load
      measurement. However, quantifying the training of elite Australian rowers is
      challenging because of (a) the multicenter, multistate structure of the national
      program; (b) the variety of training undertaken; and (c) the limitations of
      existing methods for quantifying the loads accumulated from varied training
      formats. Therefore, the purpose of this project was to develop a new measure for
      quantifying training loads in rowing (the T2minute method). Sport scientists and
      senior coaches at the National Rowing Center of Excellence collaborated to
      develop the measure, which incorporates training duration, intensity, and mode to
      quantify a single index of training load. To account for training at different
      intensities, the method uses standardized intensity zones (T zones) established
      at the Australian Institute of Sport. Each zone was assigned a weighting factor
      according to the curvilinear relationship between power output and blood lactate
      response. Each training mode was assigned a weighting factor based on whether
      coaches perceived it to be "harder" or "easier" than on-water rowing. A common
      measurement unit, the T2minute, was defined to normalize sessions in different
      modes to a single index of load; one T2minute is equivalent to 1 minute of on
      water single scull rowing at T2 intensity (approximately 60-72% VO2max). The
      T2minute method was successfully implemented to support national training
      strategies in Australian high performance rowing. By incorporating duration,
      intensity, and mode, the T2minute method extends the concepts that underpin
      current load measures, providing 1 consistent system to quantify loads from
      varied training formats.

PMID- 24077377
TI  - Performance trends in large 10-km road running races in the United States.
AB  - Our study examines the current trends of runners participating in 10-km road
      races in the United States. Finish times and ages of all runners participating in
      10 of the largest 10-km running races in the United States between 2002-2005 and
      2011 were recorded. Linear regression analysis was performed to examine the
      trends for age, sex, and finishing time for all participants completing the
      course in <1 hour. A total of 408,296 runners were analyzed. There was a
      significant annual decrease in the ratio of men to women finishers (p < 0.001, r
      = 0.976). The average finishing time of the top 10 (men, p <= 0.05), 100 (men and
      women, p <= 0.05), and 1,000 (men and women, p < 0.01) significantly decreased
      annually. The total number of subhour finishers increased annually across all
      races (194 men per year, r = 0.584, p = 0.045; 161 women per year, r = 0.779, p =
      0.008), whereas the percentage of overall finishers completing the course in less
      than an hour significantly declined for men and women (p <= 0.003). There was a
      significant trend toward younger men in all top groups except for the single
      fastest runner (p <= 0.017). Our study demonstrates that for large 10-km U.S.
      races: the top men and women seem to be getting faster; there are more subhour
      finishers, with increasingly more women accomplishing this feat compared with
      men; an increasingly lower percentage of overall finishers is finishing in <1
      hour; and the fastest men are also increasingly younger.

PMID- 24077378
TI  - The Effect of Intermittent Arm and Shoulder Cooling on Baseball Pitching
      Velocity.
AB  - The throwing arm of a baseball pitcher is subjected to high stress as a result of
      the repetitive activity of pitching. Intermittent cryotherapy may facilitate
      recovery from this repeated high stress, but few researchers have investigated
      cryotherapy's efficacy in an ecologically valid setting. This study investigated
      the effects of intermittent cryotherapy on pitching velocity and subjective
      measures of recovery and exertion in a simulated baseball game. Trained college
      aged male baseball pitchers (n = 8) threw 12 pitches (1 pitch every 20 seconds)
      per inning for 5 total innings during a simulated pitching start. Between each
      inning, pitchers received shoulder and arm cooling (AC) or, on a separate
      occasion, no cooling (NC). All sessions took place in a temperate environment
      (18.3 +/- 2.8 degrees  C; 49 +/- 4% relative humidity). Pitch speeds were
      averaged for each participant each inning and overall for 5 innings. Perceived
      exertion (rating of perceived exertion [RPE]) was recorded at the end of each
      simulated inning. Perceived recovery (perceived recovery scale [PRS]) was
      recorded after treatment between each inning. Mean pitching velocity for all
      innings combined was higher (p = 0.04) for shoulder and elbow cooling (AC) (31.2
      +/- 2.1 m.s) than for no cooling (NC) (30.6 +/- 2.1 m.s). Average pitch speed was
      significantly higher in the fourth (p = <0.01) and fifth (p = 0.02) innings in AC
      trial (31.3 +/- 2 m.s for both innings) compared with NC trial (30.0 +/- 2.22 m.s
      and 30.4 +/- 1.99 m.s, for the fourth and fifth innings, respectively. AC
      resulted in a significantly lower RPE (p <= 0.01) and improved PRS (p <= 0.01)
      compared with NC. Intermittent cryotherapy attenuated velocity loss in baseball
      pitching, decreased RPE, and facilitated subjective recovery during a 5-inning
      simulated game.

PMID- 24077379
TI  - Characteristics of shoulder impingement in the recreational weight-training
      population.
AB  - Despite reports implicating subacromial impingement syndrome (SIS) as an
      etiologic source of shoulder pain among weight-training (WT) participants, a
      paucity of case-controlled evidence exists to support this premise. The purpose
      of this study was to determine whether WT participants present with
      characteristics of SIS. Additionally, we investigated the role of exercise
      selection among those identified as having SIS. Seventy-seven (154 shoulders) men
      (mean age, 28) were recruited, including 46 individuals who engaged in WT a
      minimum of 2 days per week; and 31 controls with no history of WT participation.
      Before testing, participants completed a questionnaire summarizing their training
      patterns. On completing questionnaire, 2 previously validated tests used to
      identify SIS were performed on both groups and included the painful arc sign and
      Hawkins-Kennedy test. When clustered, these tests have a positive likelihood
      ratio of 5.0 for identifying SIS when compared with diagnostic gold standards.
      Analysis identified significant between-group differences in the combined
      presence of a positive painful arc and Hawkins-Kennedy (p < 0.001) test. A
      significant association existed between clinical characteristics of SIS (p <=
      0.004) and both lateral deltoid raises and upright rows above 90 degrees .
      Conversely, a significant inverse association was found between external rotator
      strengthening and characteristics of SIS. Results suggest that WT participants
      may be predisposed to SIS. Avoiding performance of lateral deltoid raises and
      upright rows beyond an angle of 90 degrees  and efforts to strengthen the
      external rotators may serve as a useful means to mitigate characteristics
      associated with SIS.

PMID- 24077380
TI  - Static stretching and performance in multiple sets in the bench press exercise.
AB  - The purpose of this study was to analyze the acute effect of static stretching on
      the performance of multiple sets in the bench press (BP) exercise. Fifteen men
      (26.2 +/- 0.7 years, 72.4 +/- 1.3 kg, 1.78 +/- 0.1 m, 22.8 +/- 0.3 kg.m)
      performed 4 sets of the BP exercise at 80% of 1 repetition maximum until
      concentric failure, both in the stretching condition (SC) and control condition
      (CC). The rate of force decline between the first and the fourth set was used as
      fatigue index. A randomized, counterbalanced, crossover design was performed with
      48 hours between each session. Two static stretching exercises (pectoral and
      triceps brachii muscles) were performed in a single set before BP in SC, whereas
      in CC, subjects remained at rest for 150 seconds. For each stretching exercise,
      the muscle was held at the maximal stretched position for 30 seconds. No
      significant difference (p > 0.05) was identified for total repetitions performed
      in 4 sets (SC, 21.3 +/- 0.7% vs. CC, 20.5 +/- 0.7%) and in the fatigue index (SC,
      75.5 +/- 1.3% vs. CC, 73.2 +/- 1.9%). The results suggest that the performance of
      multiple sets in the BP exercise does not seem to be influenced by previous
      static stretching.

PMID- 24077381
TI  - Vibration training for upper body: transmission of platform vibrations through
      cables.
AB  - The aim of the present study was to evaluate the vibration transmission from a
      vibration platform through Vectran cables to the upper body and its relationship
      to induced muscular activation. Fifteen clinically healthy participants performed
      3 different arm exercises-biceps curl, triceps curl, and lateral raise. Vibration
      transmission to the upper body was assessed over a wide range of accelerations
      (from 1.90 to 5.98 g) and frequencies (from 25 to 40 Hz). To assess the vibration
      transmission, 7 triaxial accelerometers were attached from the hand up to the
      head, and the root-mean-square of acceleration signal of each site-specific body
      point was calculated. Muscular activity of biceps brachii, triceps brachii,
      deltoid, and upper trapezius was recorded. The results showed a significant
      attenuation of the platform accelerations transmitted through the Vectran cables
      to the upper body. Handle vibration ranged between 27 and 44% of the acceleration
      delivered by the platform depending on platform vibration parameters
      (acceleration/frequency). Vibration increased the muscle activity of biceps
      brachii, triceps brachii, deltoid, and upper trapezius muscles significantly only
      during biceps curl exercises. No frequency or acceleration effect was found on
      the size of the muscle response. The results of the present study suggest that a
      cable-pulley resistance system on a vibration platform channels the vibration
      safely from the platform to the arms and induces additional muscle activation in
      some arm muscles when biceps curl exercises are performed.

PMID- 24077382
TI  - An examination of the strength and electromyographic responses after concentric
      vs. eccentric exercise of the forearm flexors.
AB  - The purpose of this study was to examine the strength and electromyographic (EMG)
      responses in exercised and nonexercised limbs after concentric (CON) vs.
      eccentric (ECC) exercise of the forearm flexors. Twenty-five men (mean +/- SD
      age, 23.6 +/- 3.8 years; height, 179.7 +/- 6.6 cm; body weight, 87.4 +/- 14.6 kg)
      performed 6 sets of 10 maximal CON isokinetic (CON exercise) or ECC isokinetic
      (ECC exercise) muscle actions of the dominant (DOM) forearm flexors on 2 separate
      randomly ordered visits. Each subject performed isometric maximal voluntary
      contractions (MVCs) of both the DOM and nondominant (NONDOM) forearm flexors
      before (PRE) and immediately after (POST) the exercise interventions. The DOM
      limb was the only limb exercised for both interventions. A bipolar EMG signal was
      detected from the biceps brachii during each MVC. The results showed that there
      were significant 17 and 21% decreases in maximal strength after the CON exercise
      and ECC exercise, respectively. When collapsed across exercise conditions,
      strength for the DOM and NONDOM limbs significantly decreased 36 and 4% after
      exercise, respectively. Accompanied with the strength losses, normalized EMG
      amplitude for the DOM and NONDOM limbs also reduced 21 and 7%, respectively.
      These findings suggested that the CON exercise and ECC exercise interventions
      caused similar strength losses for the exercised arm. There was also a strength
      loss in the contralateral nonexercised arm that was likely because of neural
      factors.

PMID- 24077383
TI  - Peristaltic pulse dynamic compression of the lower extremity enhances
      flexibility.
AB  - This study investigated the effects of peristaltic pulse dynamic compression
      (PPDC) on range-of-motion (ROM) changes in forward splits. Serious stretching
      usually involves discomfort and large time investments. Tissue structural changes
      and stretch tolerance have heretofore been considered the primary mechanisms of
      enhanced ROM. The PPDC treatment was computer controlled. Circumferential and
      segmented inflation pressures were induced by feet to hip leggings. Nine
      subjects, experienced in stretching and a forward split position, volunteered.
      The subjects were familiarized with the protocol and randomly assigned to an
      initial condition: experimental (PPDC), or control (CONT). The study involved a
      crossover design. Second conditions were tested within 1-5 days. All tests were 2
      trials of right and left forward splits. Split flexibility was assessed by
      measuring the height of the anterior superior iliac spine of the rear leg from
      the floor. Pelvic posture was controlled by rear leg position. The PPDC treatment
      was 15 minutes of seated PPDC. The control condition was the same except that
      leggings were not inflated. Pressures of 5 cells in the leggings were set at
      factory defaults, 70 mm Hg sequentially. Difference score results indicated
      statistically significant (p <= 0.05) differences by condition and the condition
      by leg interaction. The rapid acute changes in ROM (PPDC: right 25.3%, left
      33.3%; CONT: right 12.2%, left 1.0%) support the premise that changes in ROM were
      dependent on mechanisms other than tissue structural changes and/or stretch
      tolerance. PPDC provides a means of rapidly enhancing acute ROM requiring less
      discomfort and time.

PMID- 24077384
TI  - Cardiac autonomic recovery after a single session of resistance exercise with and
      without vascular occlusion.
AB  - The aim of this study was to investigate the heart rate variability (HRV) after
      resistance training with and without vascular occlusion. It was hypothesized that
      low intensity (LI) with vascular occlusion (LIO) would elicit comparable
      postexercise HRV responses with that of high intensity (HI) without vascular
      occlusion. Nine subjects undertook 4 experimental sessions of leg press exercise
      on different days: (a) 1 repetition maximum (1RM) test, (b) 4 sets of 8
      repetitions + 1 set until exhaustion at 80% of 1RM without vascular occlusion
      (HI), (c) 4 sets of 16 repetitions + 1 set until exhaustion at 40% of 1RM with
      vascular occlusion (LIO), and (d) 4 sets of 16 repetitions + 1 set with the
      number of repetitions equal to the last set of LIO but at 40% of 1RM without
      vascular occlusion (LI). Heart rate variability was analyzed 10 minutes, 20
      minutes, 30 minutes, 1 hour, 5 hours, and 24 hours after the HI, LIO, and LI
      sessions. The HI session increased the heart rate (HR) and reduced the root mean
      square of the successive difference of R-R intervals (RMSSD) and log-transformed
      high-frequency (lnHF) power during prolonged recovery (HR = 5 hours; RMSSD = 30
      minutes; lnHF = 1 hour) at a greater magnitude when compared with LIO and LI.
      Despite the same intensity of exercise for LIO and LI, the occlusion delayed the
      recovery of HR and HRV variables. Postexercise blood lactate concentration was
      moderate to strongly correlated with peak HR (r = 0.87), RMSSD (r = -0.64), and
      lnHF (r = -0.68). This study has demonstrated that LIO was able to reduce cardiac
      autonomic stress when compared with HI.

PMID- 24077385
TI  - Shaken adult syndrome: report of 2 cases.
AB  - IMPORTANCE: To establish that the intracranial and ophthalmologic findings
      present in victims of abusive head trauma can also be seen in shaken adults.
      OBSERVATIONS: We report 2 cases of shaken adults with intracranial and
      ophthalmologic findings that resulted from repetitive acceleration-deceleration
      injury. These findings included intracranial hemorrhages, hemorrhages involving
      the optic nerve sheath, intraretinal and subretinal hemorrhages, and macular
      folds. CONCLUSIONS AND RELEVANCE: The intracranial and ophthalmologic findings
      that are characteristic of abusive head trauma--subdural hemorrhages, optic nerve
      sheath hemorrhages, and retinal hemorrhages--are generally thought to be limited
      to young children and infants. Adults may also be victims of shaking abuse, and
      an ophthalmic examination may be beneficial when shaking is suspected.

PMID- 24077386
TI  - Non-wetting droplets on hot superhydrophilic surfaces.
AB  - Controlling wettability by varying surface chemistry and roughness or by applying
      external stimuli is of interest for a wide range of applications including
      microfluidics, drag reduction, self-cleaning, water harvesting, anti-corrosion,
      anti-fogging, anti-icing and thermal management. It has been well known that
      droplets on textured hydrophilic, that is superhydrophilic, surfaces form thin
      films with near-zero contact angles. Here we report an unexpected behaviour where
      non-wetting droplets are formed by slightly heating superhydrophilic
      microstructured surfaces beyond the saturation temperature (>5  degrees C).
      Although such behaviour is generally not expected on superhydrophilic surfaces,
      an evaporation-induced pressure in the structured region prevents wetting. In
      particular, the increased thermal conductivity and decreased vapour permeability
      of the structured region allows this behaviour to be observed at such low
      temperatures. This phenomenon is distinct from the widely researched Leidenfrost
      and offers an expanded parametric space for fabricating surfaces with desired
      temperature-dependent wettability.

PMID- 24077387
TI  - A systematic review of predictors and moderators of response to psychological
      therapies in OCD: do we have enough empirical evidence to target treatment?
AB  - Obsessive-compulsive disorder (OCD) is a disabling mental health condition.
      Despite effective psychological treatments for OCD, a significant percentage of
      patients fail to experience lasting benefit. Factors underlying variable
      treatment response are poorly understood. Moderators of outcome can help
      understand "for whom" and "under what circumstances" an intervention works best
      and thus improve service effectiveness. This paper synthesizes the evidence on
      predictors and moderators and assesses the quality of reporting of related
      analyses in psychological therapies for adults with OCD. Trials were identified
      through electronic searches (CENTRAL, MEDLINE, PsycINFO, EMBASE), key author, and
      reference list searches of relevant systematic reviews. Fifty five percent
      (38/69) of relevant trials reported baseline factors associated with outcome;
      these encompassed clinical, demographic, interpersonal, OCD symptom-specific,
      psychological/psychosocial, and treatment-specific variables. Predictors were
      commonly assessed via a validated pre-randomization measure, though few trials
      adopted best practice by stating a priori hypotheses or conducting a test of
      interaction. Potential associations emerged between worse OCD treatment outcome
      and the following factors: hoarding pathology, increased anxiety and OCD symptom
      severity, certain OCD symptom subtypes, unemployment, and being single/not
      married. However, the applied utility of these analyses is currently limited by
      methodological weaknesses. 

PMID- 24077388
TI  - Symmetry breaking gives rise to energy spectra of three states of matter.
AB  - A fundamental task of statistical physics is to start with a microscopic
      Hamiltonian, predict the system's statistical properties and compare them with
      observable data. A notable current fundamental challenge is to tell whether and
      how an interacting Hamiltonian predicts different energy spectra, including
      solid, liquid and gas phases. Here, we propose a new idea that enables a unified
      description of all three states of matter. We introduce a generic form of an
      interacting phonon Hamiltonian with ground state configurations minimising the
      potential. Symmetry breaking SO(3) to SO(2), from the group of rotations in
      reciprocal space to its subgroup, leads to emergence of energy gaps of shear
      excitations as a consequence of the Goldstone theorem, and readily results in the
      emergence of energy spectra of solid, liquid and gas phases. 

PMID- 24077389
TI  - Electrochemical fabrication of ZnO-CdSe core-shell nanorod arrays for efficient
      photoelectrochemical water splitting.
AB  - Efficient hydrogen production from photoelectrochemical (PEC) water splitting is
      a promising route to solve the approaching energy crisis. Herein, we report a
      facile all-electrochemical approach to fabricate well-aligned ZnO-CdSe core-shell
      nanorod arrays with excellent uniformity on transparent indium tin oxide (ITO)
      substrates. The shell thickness of the core-shell nanorods can be tuned precisely
      by adjusting the charge density passing through the working electrode during the
      deposition of CdSe quantum dots (QDs). The optimized ZnO-CdSe nanorod arrays
      showed excellent PEC performance with a significant saturated photocurrent
      density of 14.9 mA cm(-2) at 0.8 V (vs. RHE) under AM 1.5 illumination, which is,
      to the best of our knowledge, the highest value ever reported for similar
      nanostructures, owing to the favourable band alignment and good distribution of
      CdSe QDs on ZnO nanorods. Our results demonstrate that the electrochemically
      deposited ZnO-CdSe nanorod arrays can be utilized as efficient photoanodes in PEC
      water splitting cells. 

PMID- 24077390
TI  - The evolution of evolvability in microRNA target sites in vertebrates.
AB  - The lack of long-term evolutionary conservation of microRNA (miRNA) target sites
      appears to contradict many analyses of their functions. Several hypotheses have
      been offered, but an attractive one-that the conservation may be a function of
      taxonomic hierarchy (vertebrates, mammals, primates, etc.)-has rarely been
      discussed. For such an analysis, we cannot use evolutionary conservation as a
      criterion of target identification, and hence, have used high confidence target
      sites in the cross-linking immunoprecipitation (CLIP) data. Assuming that a
      proportion, p, of target sites in the CLIP data are conserved, we define the
      evolvability of miRNA targets as 1-p. Genomic data from vertebrate species show
      that the evolvability between human and fish is very high, at more than 90%. The
      evolvability decreases to 50% between birds and mammals, 20% among mammalian
      orders, and only 6% between human and chimpanzee. Within each taxonomic
      hierarchy, there is a set of targets that are conserved only at that level of
      evolution. Extrapolating the evolutionary trend, we find the evolvability in any
      single species to be close to 0%. Thus, all miRNA target sites identified by the
      CLIP method are evolutionarily conserved in one species, but the conservation is
      lost step by step in larger taxonomic groups. The changing evolvability of miRNA
      targets suggests that miRNA-target interactions may play a role in the evolution
      of organismal diversity. 

PMID- 24077391
TI  - High-throughput chromatin motion tracking in living yeast reveals the flexibility
      of the fiber throughout the genome.
AB  - Chromosome dynamics are recognized to be intimately linked to genomic
      transactions, yet the physical principles governing spatial fluctuations of
      chromatin are still a matter of debate. Using high-throughput single-particle
      tracking, we recorded the movements of nine fluorescently labeled chromosome loci
      located on chromosomes III, IV, XII, and XIV of Saccharomyces cerevisiae over an
      extended temporal range spanning more than four orders of magnitude (10(-2)-10(3)
      sec). Spatial fluctuations appear to be characterized by an anomalous diffusive
      behavior, which is homogeneous in the time domain, for all sites analyzed. We
      show that this response is consistent with the Rouse polymer model, and we
      confirm the relevance of the model with Brownian dynamics simulations and the
      analysis of the statistical properties of the trajectories. Moreover, the
      analysis of the amplitude of fluctuations by the Rouse model shows that yeast
      chromatin is highly flexible, its persistence length being qualitatively
      estimated to <30 nm. Finally, we show that the Rouse model is also relevant to
      analyze chromosome motion in mutant cells depleted of proteins that bind to or
      assemble chromatin, and suggest that it provides a consistent framework to study
      chromatin dynamics. We discuss the implications of our findings for yeast genome
      architecture and for target search mechanisms in the nucleus. 

PMID- 24077393
TI  - Advertising, expectations and informed consent: the contents and functions of
      acupuncture leaflets.
AB  - OBJECTIVE: To evaluate the content of patient information leaflets about
      acupuncture. METHODS: 401 patient information leaflets were obtained from
      practising UK acupuncturists and subjected to content and thematic analysis.
      RESULTS: 59% of included leaflets were from NHS physiotherapists. Almost all the
      leaflets defined acupuncture and the majority explained how it might work,
      described the treatment process and placed it in a historical context. Most
      described possible benefits and risks of acupuncture and discussed
      contraindications and safety. Just under a third of leaflets (120, 30%) suggested
      conditions that might be helped by acupuncture, most commonly musculoskeletal
      pain, arthritis and injuries. By emphasising differences between individuals in
      acupuncture treatments and responsiveness, the leaflets fostered hope for
      positive effects without making any guarantees. CONCLUSIONS: Information leaflets
      are broadly consistent with the evidence for acupuncture, but some claims are
      inconsistent with official advice from advertising regulators. An ethically
      sound, scientifically grounded and psychologically effective leaflet should
      accurately convey both benefits and risks of treatment, optimise patients'
      expectations and allay concerns about needling. This study suggests that
      acupuncture leaflets might achieve these multiple functions but care should be
      taken to ensure adequate coverage of risks.

PMID- 24077392
TI  - Hominoid fission of chromosome 14/15 and the role of segmental duplications.
AB  - Ape chromosomes homologous to human chromosomes 14 and 15 were generated by a
      fission event of an ancestral submetacentric chromosome, where the two
      chromosomes were joined head-to-tail. The hominoid ancestral chromosome most
      closely resembles the macaque chromosome 7. In this work, we provide insights
      into the evolution of human chromosomes 14 and 15, performing a comparative study
      between macaque boundary region 14/15 and the orthologous human regions. We
      construct a 1.6-Mb contig of macaque BAC clones in the region orthologous to the
      ancestral hominoid fission site and use it to define the structural changes that
      occurred on human 14q pericentromeric and 15q subtelomeric regions. We
      characterize the novel euchromatin-heterochromatin transition region (~20 Mb)
      acquired during the neocentromere establishment on chromosome 14, and find it was
      mainly derived through pericentromeric duplications from ancestral hominoid
      chromosomes homologous to human 2q14-qter and 10. Further, we show a relationship
      between evolutionary hotspots and low-copy repeat loci for chromosome 15,
      revealing a possible role of segmental duplications not only in mediating but
      also in "stitching" together rearrangement breakpoints. 

PMID- 24077394
TI  - A smooth polaron-molecule crossover in a Fermi system.
AB  - The problem of a single down-spin particle interacting with a Fermi sea of up
      spin particles is of current interest in the field of cold atoms. The Hubbard
      model, appropriate to atoms in an optical lattice potential, is considered in
      parallel with a gas model. As the strength of an attractive short-range
      interaction is increased there is a crossover from 'polaron' behaviour, in which
      the Fermi sea is weakly perturbed, to 'molecule' behaviour in which the down-spin
      particle is bound to a single up-spin particle. It is shown that this is a smooth
      crossover, not a sharp transition as claimed by many authors. 

PMID- 24077395
TI  - New development on materials and techniques used in the heraldic designs of
      illuminated Manueline foral charters by multi-analytical methods.
AB  - In the illuminated foral charters commissioned by D. Manuel I, King of Portugal
      (1495-1521), heraldry played a prominent role. In this work, royal emblems
      corresponding to the third heraldic design, applied to the Charter of Couto de
      Teixedo, are studied by means of EDXRF, SEM-EDS, micro-Raman, micro-FTIR and HPLC
      DAD to characterize the materials and techniques used to produce this masterpiece
      of Portuguese Renaissance. By comparing this data with the results previously
      obtained in other three charters, this research allows for the first time an
      accurate insight into the reformed manuscripts production, especially since the
      illuminated charters under consideration were all investigated on the basis of
      similar micro-spectroscopic techniques. Inks, metal coatings, pigments, organic
      dyes, fillers or extenders, and binding media are discussed, and their use
      enlightened by the politic and legal messages the foral charters had to convey.
      Parchment analysis allowed us to identify the animal species, and all undertaken
      processes along its preparation. HPLC-DAD allowed us to differentiate the gums
      used. CaSO4 was observed in the parchment as a degradation product of CaCO3 used
      in parchment production in the presence of metal sulfates coming from the ink.
      Pigments used in the different colors as well as some specific phases for some
      colors were identified. Silvering and gilding processes, metal caratage and
      silver oxidation compounds were also objects of the present study.

PMID- 24077399
TI  - Sol-gel microencapsulation of odorants and flavors: opening the route to
      sustainable fragrances and aromas.
AB  - The sol-gel approach to encapsulate fragrance and aroma chemicals in porous
      silica-based materials has the potential to afford odorant and flavoured
      materials with novel and unique beneficial properties. Amorphous sol-gel SiO2 is
      non-toxic and safe, whereas the sol-gel entrapment of delicate chemicals in its
      inner pores results in pronounced chemical and physical stabilization of the
      entrapped actives, thereby broadening the practical utilization of chemically
      unstable essential oils. Reviewing progress in the fabrication of diverse odorant
      and flavoured sol-gels, we show how different synthetic strategies afford
      advanced materials suitable for practical application with important health and
      environmental benefits. 

PMID- 24077398
TI  - Pair distribution function computed tomography.
AB  - An emerging theme of modern composites and devices is the coupling of
      nanostructural properties of materials with their targeted arrangement at the
      microscale. Of the imaging techniques developed that provide insight into such
      designer materials and devices, those based on diffraction are particularly
      useful. However, to date, these have been heavily restrictive, providing
      information only on materials that exhibit high crystallographic ordering. Here
      we describe a method that uses a combination of X-ray atomic pair distribution
      function analysis and computed tomography to overcome this limitation. It allows
      the structure of nanocrystalline and amorphous materials to be identified,
      quantified and mapped. We demonstrate the method with a phantom object and
      subsequently apply it to resolving, in situ, the physicochemical states of a
      heterogeneous catalyst system. The method may have potential impact across a
      range of disciplines from materials science, biomaterials, geology, environmental
      science, palaeontology and cultural heritage to health.

PMID- 24077400
TI  - Recent advances in the treatment of melanoma.

PMID- 24077402
TI  - Videoscopic inguinal lymphadenectomy for metastatic melanoma.
AB  - BACKGROUND: The standard treatment of care for melanoma metastatic to the
      inguinal lymph node basin is lymphadenectomy. However, up to 50% of patients
      forgo the operation partly due to concerns about morbidity. Videoscopic inguinal
      lymphadenectomy (VIL) is a minimally invasive technique designed to minimize
      wound complications while achieving comparable oncological control. METHODS: We
      reviewed pertinent literature related to open inguinal lymphadenectomy and VIL
      specific to melanoma, offering personal experience where appropriate. RESULTS:
      Despite efforts to minimize the complications of open inguinal lymphadenectomy,
      approximately 50% of patients experience a wound-related complication. However,
      performing minimally invasive VIL has led to a significant decrease in length of
      hospital stay, a decrease in complications, and equivalent or superior lymph node
      retrieval in patients with metastatic melanoma to the inguinal basin.
      CONCLUSIONS: VIL is an alternative to open inguinal lymphadenectomy for patients
      with melanoma and regional metastases.

PMID- 24077401
TI  - Identifying risk factors using a skin cancer screening program.
AB  - BACKGROUND: The incidence of melanoma and nonmelanoma skin cancer continues to
      increase. To detect lesions at an earlier phase in their progression, skin cancer
      screening programs have been advocated by some. However, the effectiveness of
      skin cancer screening and the ideal population that these screenings should
      target have yet to be firmly established. This study details the relationship of
      a group of well-known risk factors with presumptive diagnoses in a large series
      of individuals self-referred for free skin cancer screening. METHODS: Data
      obtained during 2007 to 2010 from a descriptive cross-sectional study skin cancer
      screening program are presented. Participant history was recorded using
      standardized medical history forms prior to skin examination. Screeners conducted
      a skin examination varying from whole-body to limited areas (per participant
      preference) and recorded diagnoses. Diagnoses were assigned to the nonmelanoma
      cancer (NMC) or suspicious pigmented lesion group for analysis. RESULTS: A
      presumptive diagnosis of NMC was associated with male sex, age >= 50 years,
      personal history of skin cancer, lower skin phototype, increased sunscreen use,
      and increased chronic sun exposure (all P values <= .0001). After controlling for
      skin phototype, increased sunscreen use was not associated with a presumptive
      diagnosis of NMC (P = .96). Presumptive diagnosis of a suspicious pigmented
      lesion was associated with a reported history of "changing mole" (P < .0001) and
      negatively associated with age >= 50 years (P < .0001) and a personal history of
      skin cancer (P = .0119). CONCLUSIONS: Several known risk factors for nonmelanoma
      skin cancer correlated with a presumptive diagnosis of NMC. The yield of
      presumptive atypical pigmented lesions was increased in participants aged < 50
      years, supporting the notion that this population may benefit from screening.

PMID- 24077403
TI  - Melanoma mutagenesis and aberrant cell signaling.
AB  - BACKGROUND: Malignant melanoma is the most fatal type of skin cancer. Traditional
      melanoma classification has been based on histological subtype or anatomical
      location. However, recent evidence suggests that melanoma comprises a group of
      diseases characterized by distinct molecular mutations. These mutations affect
      disease behavior but provide unique opportunities for targeted therapy. METHODS:
      In this review, several signaling pathways in melanoma are described as well as
      how mutations of BRAF, NRAS, KIT, GNAQ, and GNA11 genes cause aberrant signaling
      and malignant transformation. RESULTS: Multiple genes affecting both the mitogen
      activated protein kinase (MAPK) and phosphatidylinositol 3-kinase (PI3K) pathway
      are mutated in melanoma. Melanomas harboring the BRAF V600E mutation have
      demonstrated sensitivity to both RAF and MAPK/extracellular signal regulated
      kinase (ERK) inhibitors in vitro and in vivo. In addition, KIT-mutant melanomas,
      often arising from mucosal, acral, and chronically sun-damaged skin surfaces,
      have shown clinical response to several inhibitors of the type III transmembrane
      receptor tyrosine kinase KIT. Uveal melanoma, which often harbors GNAQ or GNA11
      mutations, may also be sensitive to MAPK/ERK or protein kinase C/PI3K pathway
      inhibition. CONCLUSIONS: Emerging knowledge of these molecular alterations has
      led to clinical advances in patients with melanoma. The study of known mutations
      and identification of new potential targets must continue in an effort to develop
      more effective therapies for this disease.

PMID- 24077404
TI  - New targeted therapies in melanoma.
AB  - BACKGROUND: The previous 2 years have been an exciting time in melanoma research,
      due in part to the approval of vemurafenib and ipilimumab for advanced melanoma.
      Increased knowledge of the molecular biology leading to melanoma has led to the
      development of several new agents that target specific oncogenes. METHODS: The
      authors review the latest developments in signal transduction inhibitors and in
      immune modulators for the treatment of melanoma. Investigational agents currently
      in development are also discussed. RESULTS: Vemurafenib and ipilimumab have
      improved overall survival in patients with metastatic melanoma. Many new agents
      are in development, including programmed death-1 antibodies and combination
      signal transduction inhibitors. CONCLUSIONS: A recognition of the genetic
      diversity of melanoma and a better understanding of the immune system have
      resulted in improvements in overall survival in patients with metastatic
      melanoma. Refractory cases remain challenging, and combination therapies are
      being explored in an effort to overcome resistance mechanisms. New molecular
      targets need to be identified to help the subset of patients who do not harbor
      BRAF mutations.

PMID- 24077405
TI  - Adoptive cell transfer for patients with metastatic melanoma: the potential and
      promise of cancer immunotherapy.
AB  - BACKGROUND: Current FDA-approved therapeutic options for patients with metastatic
      melanoma include dacarbazine, interleukin 2, ipilimumab, vemurafenib, dabrafenib,
      and trametinib, but long-term tumor regression using available agents remains out
      of reach for most patients. Adoptive cell transfer (ACT) with autologous tumor
      infiltrating lymphocytes (TILs) has shown encouraging results in clinical trials,
      with evidence of durable ongoing complete responses in patients with advanced
      melanoma. Emerging techniques to engineer T-cell receptors (TCRs) or chimeric
      antigen receptors (CARs) using lymphocytes from peripheral blood may offer new
      tactics in ACT. METHODS: We reviewed the literature to provide a synopsis on the
      development and clinical trial results of ACT, as well as the future outlook for
      using ACT in patients with metastatic melanoma. RESULTS: ACT with TILs as part of
      a lymphodepleting regimen has been shown in clinical trials to cause objective
      clinical responses in approximately 40% to 72% of patients with metastatic
      melanoma, with up to 40% of those patients experiencing complete responses
      lasting up to 7 years ongoing. Pilot trials using TCR-engineered cells against
      melanoma-associated antigens MART-1 and gp100 and the cancer-testis antigen NY
      ESO-1 have shown clinical responses in patients with melanoma. CAR cells directed
      against melanoma have been tested only in preclinical models; however, CAR cells
      targeting other histologies such as lymphoma have elicited antitumor responses in
      patients. CONCLUSIONS: An example of state-of-the-art personalized medicine, ACT
      is a potentially curative therapy for patients with metastatic melanoma. Ongoing
      trials aiming to simplify the regimens may allow a broader range of patients to
      be treated and enable ACT to be offered by academic cancer centers.

PMID- 24077406
TI  - Novel treatments for melanoma brain metastases.
AB  - BACKGROUND: The development of brain metastases is common in patients with
      melanoma and is associated with a poor prognosis. Treating patients with melanoma
      brain metastases (MBMs) is a major therapeutic challenge. Standard approaches
      with conventional chemotherapy are disappointing, while surgery and radiotherapy
      have improved outcomes. METHODS: In this article, we discuss the biology of MBMs,
      briefly outline current treatment approaches, and emphasize novel and emerging
      therapies for MBMs. RESULTS: The mechanisms that underlie the metastases of
      melanoma to the brain are unknown; therefore, it is necessary to identify
      pathways to target MBMs. Most patients with MBMs have short survival times.
      Recent use of immune-based and targeted therapies has changed the natural history
      of metastatic melanoma and may be effective for the treatment of patients with
      MBMs. CONCLUSIONS: Developing a better understanding of the factors responsible
      for MBMs will lead to improved management of this disease. In addition,
      determining the optimal treatments for MBMs and how they can be optimized or
      combined with other therapies, along with appropriate patient selection, are
      challenges for the management of this disease.

PMID- 24077407
TI  - Cutaneous leiomyosarcoma: treatment and outcomes with a standardized margin of
      resection.
AB  - BACKGROUND: Cutaneous leiomyosarcoma is primarily a low-grade malignancy that
      affects elderly male Caucasians. It is a rare dermal-based tumor for which
      treatment algorithms have been poorly defined. METHODS: We retrospectively
      reviewed the use of a median 1-cm margin for resection to treat patients with
      cutaneous leiomyosarcoma referred for treatment between 2005 and 2010. RESULTS:
      Thirty-three patients with cutaneous leiomyosarcoma were treated. Of these, 76%
      were male, 97% were Caucasian (median age: 63.5 years), and 67% of tumors were
      located on the extremities. Preoperative staging was negative for distant
      metastasis in all patients. A majority of the tumors (88%) were low grade (median
      size: 1.3 cm). All of the tumors were positive for smooth-muscle actin. A total
      of 94% of patients underwent primary surgical resection with a median margin of 1
      cm. Final resection margin was negative in 97% of patients. Adjuvant radiotherapy
      was used in 15%. No metastatic spread or recurrences were present, and 100% of
      patients were alive at last follow-up (median: 15.5 months). CONCLUSIONS: Good
      oncological control and excellent outcomes are possible with a 1-cm resection
      margin in most cases of cutaneous leiomyosarcoma.

PMID- 24077409
TI  - Segmentation of the thrombus of giant intracranial aneurysms from CT angiography
      scans with lattice Boltzmann method.
AB  - Computed Tomography Angiography (CTA) plays an essential role in the diagnosis,
      treatment evaluation, and monitoring of cerebral aneurysms. Segmentation of CTA
      medical images of giant intracranial aneurysms (GIA) provides quantitative
      measurements of thrombus and aneurysms geometrical characteristics allowing 3D
      reconstruction. In fact, GIA demonstrated neuroradiological features and
      propensity of partial or total spontaneous intra-aneurysmal thrombosis generating
      a thrombus. Despite intensive researches on medical image segmentation, aneurysm
      (Lumen, Thrombus, and Parent Blood Vessels) segmentation remains as a difficult
      problem that has not been yet resolved. In this paper, we proposed a Lattice
      Boltzmann Geodesic Active Contour Method (LBGM) for aneurysm segmentation in CTA
      images in order to estimate both the volumes of the thrombus and the aneurysm.
      Although the noise in the CTA images is very strong and the edges of the thrombus
      are not so different than the surrounding tissues, the aneurysms are segmented
      effectively. Based on these results, a method using a dome-neck aspect ratio (AR)
      parameter for the evaluation of the Spontaneous Thrombosis (ST) phenomena
      demonstrates the promising potentiality of this LBGM for clinical applications. 

PMID- 24077408
TI  - A serotonin-induced N-glycan switch regulates platelet aggregation.
AB  - Serotonin (5-HT) is a multifunctional signaling molecule that plays different
      roles in a concentration-dependent manner. We demonstrated that elevated levels
      of plasma 5-HT accelerate platelet aggregation resulting in a hypercoagulable
      state in which the platelet surface becomes occupied by several glycoproteins.
      Here we study the novel hypothesis that an elevated level of plasma 5-HT results
      in modification of the content of N-glycans on the platelet surface and this
      abnormality is associated with platelet aggregation. Mass spectrometry of total
      surface glycoproteins on platelets isolated from wild-type mice infused for 24
      hours with saline or 5-HT revealed that the content of glycoproteins on platelets
      from 5-HT-infused mice switched from predominantly N-acetyl-neuraminic acid
      (Neu5Ac) to N-glycolyl-neuraminic acid (Neu5Gc). Cytidine monophosphate-N
      acetylneuraminate hydroxylase (CMAH) synthesizes Neu5Gc from Neu5Ac. Up
      regulation of Neu5Gc content on the platelet surface resulted from an increase in
      the catalytic function, not expression, of CMAH in platelets of 5-HT-infused
      mice. The highest level of Neu5Gc was observed in platelets of 5-HT-infused, 5-HT
      transporter-knock out mice, suggesting that the surface delineated 5-HT receptor
      on platelets may promote CMAH catalytic activity. These new findings link
      elevated levels of plasma 5-HT to altered platelet N-glycan content, a previously
      unrecognized abnormality that may favor platelet aggregation. 

PMID- 24077411
TI  - Height restoration and preservation in osteoporotic vertebral compression
      fractures: a biomechanical analysis of standard balloon kyphoplasty versus
      radiofrequency kyphoplasty in a cadaveric model.
AB  - STUDY DESIGN: Biomechanical cadaver study. OBJECTIVE: The aim of the present
      study was to evaluate 2 different methods with respect to height restoration and
      preservation in a cadaver model under cyclic loading. SUMMARY OF BACKGROUND DATA:
      Standard balloon kyphoplasty (BKP) represents a well-established treatment
      opportunity for osteoporotic vertebral compression fractures. BKP was developed
      to restore vertebral height and improve sagittal alignment. Its use has grown
      significantly over the last 2 decades. In contrast, distinct biomechanical data
      are missing. Within the last few years, several alternative techniques with
      regard to height restoration have emerged, such as radiofrequency kyphoplasty
      (RFK). METHODS: Twenty-five vertebral bodies of 2 female cadavers with secured
      osteoporosis were examined. Standardized vertebral wedge compression fractures
      were created. Afterward, 2 groups were randomly assigned: 12 vertebral bodies
      were treated with BKP and 13 vertebral bodies by RFK under a preload of 100 N.
      Then the vertebral bodies underwent cyclic loading (100,000 cycles, 100 to 600 N,
      5 Hz). Anterior, central, and posterior vertebral body heights were evaluated by
      CT scans. RESULTS: Anterior height was reduced after fracture 6.3 mm (SD 3) for
      the BKP group and 7.2 mm (SD 3) in the RFK group (P>0.1). After treatment, the
      difference in the initial anterior height was 4.5 mm (SD 2) for the BKP group and
      4.7 mm (SD 3) for the RFK group (P>0.1). After cyclic loading, the difference was
      5.3 mm (SD 3) for the BKP group and 5.2 mm (SD 3) for the RFK group (P>0.1). The
      average cement volume used was 8.7 mL (SD 1) for the BKP group and 4.8 mL (SD 2)
      for the RFK group (P<0.0001). CONCLUSIONS: On the basis of our results, the
      unipedicular RFK in osteoporotic compression fractures might represent a
      promising alternative for the clinical setting.

PMID- 24077412
TI  - Percutaneous Pedicle Screw Placement in the Lumbar Spine: A Comparison Study
      Between the Novel Guidance System and the Conventional Fluoroscopy Method.
AB  - STUDY DESIGN: The clinical study was conducted on 145 patients who received
      either a novel guidance method or a conventional fluoroscopic method for the
      percutaneous pedicle screw placement in the lumbar spine. OBJECTIVE: The aim of
      this study was to introduce a novel guidance method for percutaneous pedicle
      screw placement and to compare it with the conventional fluoroscopic method.
      SUMMARY OF BACKGROUND DATA: Conventional fluoroscopic method was associated with
      a long screw placement and a more fluoroscopy time. The novel guidance system
      effectively minimized the insertion and the radiation exposure times. METHODS: A
      total of 145 patients were divided into 2 groups. A total of 65 patients (group
      A) underwent 152 percutaneous pedicle screw fixation by conventional fluoroscopic
      method. A total of 80 patients (group B) underwent 185 percutaneous pedicle screw
      fixation by a novel guidance method. Age, body mass index, and sex ratio were
      comparable between the 2 groups (P>0.05). The time of insertion, radiation
      exposure, and accuracy of the screw placement between the 2 groups were compared.
      RESULTS: The mean time for a single pedicle screw placement was found to be
      15.11+/-3.32 minutes in group A and 10.35+/-2.82 minutes in group B,
      respectively. The average radiation exposure was 9.06+/-2.15 s in group B and
      13.07+/-3.06 s in group A, respectively. The differences were statistically
      significant for both screw placement and radiation exposure times (P<0.05). A
      total of 131 screws (86.2%) in group A and 163 screws (88.1%) in group B were
      perfectly located within the pedicle. The statistical difference was not
      significant (chi=0.277, P=0.598). CONCLUSIONS: The novel guidance system
      significantly reduced the insertion time and radiation exposure, provided the
      screw placement was accurately performed when compared with the conventional
      method.

PMID- 24077413
TI  - The Compensatory Relationship of Upper and Subaxial Cervical Motion in the
      Presence of Cervical Spondylosis.
AB  - STUDY DESIGN: This study was an in vivo kinematic magnetic resonance imaging
      analysis of cervical spinal motion in human subjects. OBJECTIVE: The objective of
      the study was to identify associations between disk degeneration in the subaxial
      cervical spine and upper cervical spinal motion in patients with general age
      related cervical spondylosis. SUMMARY OF BACKGROUND DATA: The kinematic
      relationship between the occipital-atlantoaxial complex and subaxial cervical
      spine in patients with cervical spondylosis and decreased cervical motion is not
      well understood. METHODS: A total of 446 symptomatic patients who had neck pain
      with and without neurogenic symptoms were included in this study. Kinematic
      magnetic resonance imaging was performed with dynamic motion of the cervical
      spine in upright, weight-bearing neutral, flexion, and extension positions.
      Intervertebral disk degeneration for each segment from C2-3 to C7-T1 and sagittal
      angular motion between flexion and extension for each segment from Oc-C1 to C7-T1
      was evaluated. Depending on the amount of sagittal subaxial angular motion, the
      patients were classified into 3 groups by sagittal angular motion using cutoff
      points based on tertile (<36-degree group: 149 cases; 36-47-degree group: 148
      cases; and >47-degree group: 149 cases). RESULTS: A significant correlation was
      found between subaxial angular motion and intervertebral disk degeneration,
      indicating that the subaxial motion decreases according to the degree of disk
      degeneration. Mean angular motion of the occipital-atlantoaxial complex,
      especially of Oc-C1, was significantly higher in the <36-degree and 36-47-degree
      group than in the >47-degree group, whereas no significant difference was found
      at C1-C2. CONCLUSIONS: Our study demonstrates that decreased subaxial cervical
      spinal motion is associated with intervertebral disk degeneration in a
      symptomatic population. This decrease in mobility at the subaxial cervical spine
      is compensated for by an increase in angular mobility of the upper cervical spine
      at the occipital-atlantoaxial complex, especially at Oc-C1.

PMID- 24077416
TI  - Fusion Rates of Different Anterior Grafts in Thoracolumbar Fractures.
AB  - STUDY DESIGN: Retrospective CT analysis of anterior fusion in thoracolumbar
      trauma. OBJECTIVE: The aim of this study was to compare fusion rates of different
      bone grafts and to analyze risk factors for pseudarthrosis. SUMMARY OF BACKGROUND
      DATA: Interbody fusion is indicated in anterior column defects. Different grafts
      are used: autologous iliac crest, titanium mesh cages filled with cancellous
      bone, and autologous ribs. It is not clear which graft offers the most reliable
      fusion. MATERIAL AND METHODS: Radiologic data of 116 patients (71 men, 45 women)
      operated for type A2, A3, B, or C fractures were analyzed. The average age was
      44.6 years (range, 16-75 y) and follow-up was 2.7 years (range, 1-9 y). All
      patients were treated by posterior instrumentation followed by an anterior graft:
      53 cases with iliac crest, 43 cases with mesh cages, and 20 with rib grafts.
      Fusion was evaluated on CT and classified into complete fusion, partial fusion,
      unipolar pseudarthrosis, and bipolar pseudarthrosis. RESULTS: Iliac crest fused
      in 66%, cages in 98%, and rib grafts in 90%. The fusion rate of cages filled with
      bone was significantly higher as the iliac graft fusion rate (P=0.002). The same
      was applied to rib grafts compared with iliac crest (P=0.041). Additional bone
      formation around the main graft, bridging both vertebral bodies, was observed in
      31 of the 53 iliac crests grafts. Pseudarthrosis occurred more often in smokers
      (P=0.042). A relationship between fracture or instrumentation types, sex, age,
      BMI, and fusion could not be determined. CONCLUSIONS: Tricortical iliac crest
      grafts showed an unexpected high pseudarthrosis rate in thoracolumbar injuries.
      Their cortical bone is dense and their fusion surface is small. Rib grafts led to
      a better fusion when used in combination with the cancellous bone from the
      fractured vertebral body. Titanium mesh cages filled with cancellous bone led to
      the highest fusion rate and built a complete bony bridge between vertebral
      bodies. Smoking seemed to influence fusion. LEVEL OF EVIDENCE: Case control
      study, Level III.

PMID- 24077418
TI  - Coronal Spinal Balance in Adult Spine Deformity Patients With Long Spinal
      Fusions: A Minimum 2- to 5-Year Follow-up Study.
AB  - STUDY DESIGN: This study was a retrospective one. OBJECTIVE: The objective of the
      study was to analyze the causes, prevalence of, and risk factors for coronal
      decompensation in long adult lumbar spinal instrumentation and fusion (from
      thoracic or upper lumbar spine) to L5 or S1. SUMMARY OF BACKGROUND DATA: Coronal
      and sagittal decompensation after long fusions for spinal deformities can affect
      outcomes negatively. There is no study reporting the natural history of coronal
      spinal balance after long spinal fusions. METHODS: A single-center retrospective
      review of data from 54 patients with spinal deformity was performed. Inclusion
      criteria were patients over 18 years with long fusions (>4 segments) to L5 or the
      pelvis who had full spine standing radiographs before surgery and up to 2-5 years
      postoperatively. Radiographic data included C7PL, magnitude of scoliotic curve,
      shoulder or pelvic asymmetry in the coronal plane, thoracic kyphosis, lumbar
      lordosis, and pelvic parameters (pelvic incidence, pelvic tilt, sacral slope).
      Coronal imbalance (CI) was considered if the C7PL was >4 cm lateral to the
      central sacral line, and sagittal imbalance (SI) was considered when the C7
      plumbline was >4 cm anterior to the middle of the upper sacral plate. Paired t
      test, chi test, and repeated measures regression analysis using demographic data
      (age, sex, body mass index), operative (previous fusion, posterior only or
      anteroposterior fusion, iliac fixation or not, decompression or not, osteotomy or
      not) and postoperative (complications, use of bracing) data, and radiographic
      parameters (including SI) were performed. RESULTS: Patients showing CI equaled 11
      (19.3%) preoperatively, remained 11 (19.3%) (4 of whom were new patients with CI)
      at 6 weeks postoperatively, and increased (P<0.001) to 18 (31.6%) (8 of them
      without initial CI) at 2-5 years follow-up. However, in terms of numeric distance
      of C7PL from the midsacrum, there was no statistically significant change
      (P>0.05) from preoperative to last follow-up. SI showed significant improvement
      (P<0.05) from preoperative to 6 weeks postoperative and no statistical
      significant change (P>0.05) from 6 weeks to 2-5 years postoperatively. Repeated
      measures regression analysis showed that the presence of osteoporosis and the
      combination of anterior approach surgery with a history of previous surgery were
      significant (P<0.05) factors predictive of changes in coronal balance.
      CONCLUSIONS: After surgical correction of spinal deformities, coronal spinal
      decompensation appears in an increased number of patients at last follow-up
      postoperatively but without significant differences in coronal plane C7PL during
      the postoperative period. Attention should be paid to patients with osteoporosis
      and those with a combination of previous same site posterior spine surgery and
      new anterior approach surgery for changes of coronal balance postoperatively.

PMID- 24077419
TI  - Magnetic entropy change in core/shell and hollow nanoparticles.
AB  - The development of positive magnetic entropy change in the case of ferromagnetic
      (FM) nanostructures is a rare occurrence. We observe positive magnetic entropy
      change in core/shell (Fe/gamma-Fe2O3) and hollow (gamma-Fe2O3) nanoparticles and
      its origin is attributed to a disordered state in the nanoparticles due to the
      random distribution of anisotropy axes which inhibits any long range FM ordering.
      The effect of the energy barrier distribution on the magnetic entropy change and
      its impact on the universal behavior based on rescaled entropy change curves for
      core/shell and hollow nanostructures is discussed. Our study emphasizes that the
      magnetic entropy change is an excellent parameter to study temperature and field
      dependent magnetic freezing in such complex nanostructures. 

PMID- 24077420
TI  - Socioeconomic and Outdoor Meteorological Determinants of Indoor Temperature and
      Humidity in New York City Dwellings.
AB  - BACKGROUND: Numerous mechanisms link outdoor weather and climate conditions to
      human health. It is likely that many health conditions are more directly affected
      by indoor rather than outdoor conditions. Yet, the relationship between indoor
      temperature and humidity conditions to outdoor variability, and the heterogeneity
      of the relationship among different indoor environments are largely unknown.
      METHODS: We use 5-14 day measures of indoor temperature and relative humidity
      from 327 dwellings in New York City for the years 2008-2011 to investigate the
      relationship between indoor climate, outdoor meteorological conditions,
      socioeconomic conditions, and building descriptors. Study households were
      primarily middle-income and located across the boroughs of Brooklyn, Queens,
      Bronx, and Manhattan. RESULTS: Indoor temperatures are positively associated with
      outdoor temperature during the warm season and study dwellings in higher
      socioeconomic status neighborhoods are significantly cooler. During the cool
      season, outdoor temperatures have little effect on indoor temperatures; however,
      indoor temperatures can range more than 10  degrees C between dwellings despite
      similar outdoor temperatures. Apartment buildings tend to be significantly warmer
      than houses and dwellings on higher floors are also significantly warmer than
      dwellings on lower floors. Outdoor specific humidity is positively associated
      with indoor specific and relative humidity, but there is no consistent
      relationship between outdoor and indoor relative humidity. CONCLUSIONS: In New
      York City, the relationship between indoor and outdoor temperature and humidity
      conditions vary significantly between dwellings. These results can be used to
      inform studies of health outcomes for which temperature or humidity is an
      established factor affecting human health and highlights the need for more
      research on the determinants of indoor climate.

PMID- 24077421
TI  - Computerized provider order entry awareness for nursing: unintended consequences
      and remediation plan.

PMID- 24077424
TI  - Returning genetic research results: study type matters.
AB  - AIM: The return of individual genetic research results has been identified as one
      of the most pressing ethical challenges warranting immediate policy attention. We
      explored the practices and perspectives of genome-wide association studies (GWAS)
      investigators on this topic. MATERIALS & METHODS: Corresponding authors of
      published GWAS were invited to participate in a semistructured interview.
      Interviews (n = 35) were transcribed and analyzed using conventional content
      analysis. RESULTS: Most investigators had not returned GWAS results. Several had
      experience returning results in the context of linkage/family studies, and many
      felt that it will become a larger issue in whole-genome/-exome sequencing.
      CONCLUSIONS: Research context and nature of the study are important
      considerations in the decision to return results. More nuanced ethical guidelines
      should take these contextual factors into account.

PMID- 24077425
TI  - Choroidal thickness in patients with a history of retinopathy of prematurity.
AB  - IMPORTANCE: The cause of reduced vision in patients with a history of retinopathy
      of prematurity (ROP) is not yet fully understood. The role of the choroid in ROP
      remains unknown and existing studies of choroidal thickness in patients with a
      history of ROP are limited. It might be helpful to understand the association of
      the choroid with ROP by measuring the choroidal thickness in patients with a
      history of ROP and correlating these findings with the visual outcome of these
      patients. OBJECTIVE: To examine choroidal thickness by spectral-domain optical
      coherence tomography in children with a history of ROP and assess the impact of
      choroidal thickness on visual acuity. DESIGN: A prospective cross-sectional
      analysis from August 2011 to September 2012. SETTING: Institutional referral
      centers. PARTICIPANTS: Children aged 6 to 14 years with a history of ROP were
      classified into the following 2 groups: patients with a history of threshold ROP
      and treatment with laser or cryotherapy (treated group) and those with regressed
      ROP who had not received any treatment (nontreated group). All of the patients
      had a normal-appearing posterior pole. INTERVENTION: Examinations of visual
      acuity, refractive errors, and optical components and measurement of choroidal
      thickness. MAIN OUTCOMES AND MEASURES: Best-corrected visual acuity, optical
      components, and optical coherence tomography findings. RESULTS: In total, 49
      patients were enrolled in the study. Patients in the treated group had a
      significantly thinner choroidal thickness than the patients in the nontreated
      group after adjusting for age, axial length, and spherical power. Choroidal
      thickness was found to be positively associated with spherical power and
      spherical equivalent and negatively associated with axial length and vitreous
      depth. In addition, a thin choroidal thickness was associated with a worse best
      corrected visual acuity. CONCLUSIONS AND RELEVANCE: Choroidal thickness is
      thinner in patients with threshold ROP compared with the patients with
      spontaneously regressed ROP. A thinner choroid is associated with worse vision in
      these patients. This study might imply the association of choroid circulation
      with ROP.

PMID- 24077426
TI  - Coma, metabolic acidosis, and methemoglobinemia in a patient with acetaminophen
      toxicity.
AB  - We present a case of early coma, metabolic acidosis and methemoglobinemia after
      substantial acetaminophen toxicity in the absence of hepatic failure. A 77-year
      old female presented to the emergency department with a decreased level of
      consciousness. She was found unresponsive by a family member in her bed, and was
      reported to be acting normally when she was last seen eight hours earlier.
      Laboratory results on arrival were: pH 7.19, sodium 139 mmol/L, chloride 106
      mmol/L, potassium 3.3 mmol/L, CO2 8 mmol/L, and an anion gap of 25. Both venous
      lactate (10.2 mmol/L) and methemoglobin (9.4 %) were elevated. The patient's
      acetaminophen concentration was markedly elevated at 7138 umol/L (1078 ug/ml).
      Hepatic enzymes and coagulation tests were normal [alanine transaminase (ALT) 8
      U/L, international normalized ratio (INR) 1.0]. Intravenous N-acetylcysteine
      (NAC) was initiated at a dose of 150 mg/kg over 15 minutes, followed by 50 mg/kg
      over the next four hours, followed by 100 mg/kg over the next 16 hours. Twenty
      four hours after admission, the anion gap metabolic acidosis had resolved, and
      the methemoglobin was 2.1%. Aminotransferases peaked at 44 U/L and INR peaked at
      1.9. A urine 5-oxoproline assay performed five days after admission was negative,
      suggesting no evidence of a 5-oxoprolinase deficiency. We describe the
      pathophysiology and discuss the literature on acetaminophen-induced coma and
      metabolic acidosis in the absence of hepatic injury; and propose mechanisms for
      associated methemoglobinemia.  

PMID- 24077427
TI  - TMS to the "occipital face area" affects recognition but not categorization of
      faces.
AB  - The human cortical system for face perception is comprised of a network of
      connected regions including the middle fusiform gyrus ("fusiform face area" or
      FFA), the inferior occipital cortex ("occipital face area" or OFA), and the
      superior temporal sulcus. The traditional hierarchical feedforward model of
      visual processing suggests information flows from early visual cortex to the OFA
      for initial face feature analysis to higher order regions including the FFA for
      identity recognition. However, patient data suggest an alternative model.
      Patients with acquired prosopagnosia, an inability to visually recognize faces,
      have been documented with lesions to the OFA but who nevertheless show face
      selective activation in the FFA. Moreover, their ability to categorize faces
      remains intact. This suggests that the FFA is not solely responsible for face
      recognition and the network is not strictly hierarchical, but may be organized in
      a reverse hierarchical fashion. We used transcranial magnetic stimulation (TMS)
      to temporarily disrupt processing in the OFA in neurologically-intact individuals
      and found participants' ability to categorize intact versus scrambled faces was
      unaffected, however face identity discrimination was significantly impaired. This
      suggests that face categorization but not recognition can occur without the
      "earlier" OFA being online and indicates that "lower level" face category
      processing may be assumed by other intact face network regions such as the FFA.
      These results are consistent with the patient data and support a non
      hierarchical, global-to-local model with re-entrant connections between the OFA
      and other face processing areas. 

PMID- 24077428
TI  - Automated activity-aware prompting for activity initiation.
AB  - Performing daily activities without assistance is important to maintaining an
      independent functional lifestyle. As a result, automated activity prompting
      systems can potentially extend the period of time that adults can age in place.
      In this paper we introduce AP, an algorithm to automate activity prompting based
      on smart home technology. AP learns prompt rules based on the time when
      activities are typically performed as well as the relationship between activities
      that normally occur in a sequence. We evaluate the AP algorithm based on smart
      home datasets and demonstrate its ability to operate within a physical smart
      environment.

PMID- 24077429
TI  - Low threshold amplified spontaneous emission from tin oxide quantum dots: a
      instantiation of dipole transition silence semiconductors.
AB  - Direct bandgap semiconductors, such as In2O3, Cu2O, and SnO2, have enormous
      applications in photochemistry, photovoltaics, and optoelectronics. Due to the
      same parity of conduction and valence bands, the dipole transition is silent in
      these direct bandgap semiconductors. The low band-to-band transition efficiency
      prevents them from high intensity light emission or absorption. Here, we report
      the fabrication of SnO2 quantum dots (QDs) with sizes less than the exciton Bohr
      radius by a facile "top-down" strategy based on laser fragmentation of SnO in
      water. The SnO2 QDs shows exciton emission at ~300 nm with a high quantum yield
      of ~17%. Amplified spontaneous exciton emission is also achieved from a thin
      layer of SnO2 QDs dispersed in PEG400 on a quartz substrate. Therefore, we have
      shown that SnO2 QDs can be a potential luminescent material suitable for the
      realization of ultraviolet B lasing devices.

PMID- 24077430
TI  - Sleep in frontotemporal dementia is equally or possibly more disrupted, and at an
      earlier stage, when compared to sleep in Alzheimer's disease.
AB  - BACKGROUND: Conversely to other neurodegenerative diseases (i.e., Alzheimer's
      disease, AD), sleep in frontotemporal dementia (FTD) has not been studied
      adequately. Although some evidence exists that sleep-wake disturbances occur in
      FTD, very little is known regarding sleep macrostructure and/or primary sleep
      disorders. OBJECTIVE: To investigate these issues in this population and compare
      them to similar issues in AD and in healthy elderly (HE). METHODS: Twelve drug
      naive behavioral-variant FTD (bvFTD) patients (7 men/5 women) of mean age 62.5 +/
      8.6 years were compared to seventeen drug-naive AD patients (8 men/9 women) of
      mean age 69.0 +/- 9.9 years and twenty drug-naive HE (12 men/8 women) of mean age
      70.2 +/- 12.5 years. All participants were fully assessed clinically, through a
      sleep questionnaire, an interview, and video-polysomnography recordings. RESULTS:
      The two patient groups were comparably cognitively impaired. However, compared to
      FTD patients, the AD patients had a statistically significant longer disease
      duration. Overall, the sleep profile was better preserved in HE. Sleep complaints
      did not differ considerably between the two patient groups. Sleep parameters and
      sleep macrostructure were better preserved in AD compared to FTD patients,
      regardless of primary sleep disorders, which occurred equally in the two groups.
      CONCLUSIONS: With respect to AD, FTD patients had several sleep parameters
      similarly or even more affected by neurodegeneration, but in a much shorter time
      span. The findings probably indicate a centrally originating sleep deregulation.
      Since in FTD patients sleep disturbances may be obvious from an early stage of
      their disease, and possibly earlier than in AD patients, physicians and
      caregivers should be alert for the early detection and treatment of these
      symptoms.

PMID- 24077432
TI  - Oral infections and orofacial pain in Alzheimer's disease: a case-control study.
AB  - BACKGROUND: Dental infections are frequent and have recently been implicated as a
      possible risk factor for Alzheimer's disease (AD). Despite a lack of studies
      investigating orofacial pain in this patient group, dental conditions are known
      to be a potential cause of pain and to affect quality of life and disease
      progression. OBJECTIVES: To evaluate oral status, mandibular function and
      orofacial pain in patients with mild AD versus healthy subjects matched for age
      and gender. METHODS: Twenty-nine patients and 30 control subjects were evaluated.
      The protocol comprised a clinical questionnaire and dental exam, research
      diagnostic criteria for temporomandibular disorders, the McGill Pain
      Questionnaire, the decayed, missing, and filled teeth index, and included a full
      periodontal evaluation. AD signs and symptoms as well as associated factors were
      evaluated by a trained neurologist. RESULTS: A higher prevalence of orofacial
      pain (20.7%, p < 0.001), articular abnormalities in temporomandibular joints (p <
      0.05), and periodontal infections (p = 0.002) was observed in the study group
      compared to the control group. CONCLUSION: Orofacial pain and periodontal
      infections were more frequent in patients with mild AD than in healthy subjects.
      Orofacial pain screening and dental and oral exams should be routinely performed
      in AD patients in order to identify pathological conditions that need treatment
      thus improving quality of life compromised due to dementia.

PMID- 24077431
TI  - In vivo diffusion tensor imaging of amyloid-beta-induced white matter damage in
      mice.
AB  - BACKGROUND: Diffusion tensor imaging (DTI) suggests the presence of white matter
      abnormality at the prodromal stage in human Alzheimer's disease (AD). OBJECTIVE:
      To use a mouse model of AD to determine whether the white matter abnormality
      detected by in vivo DTI is associated with functional deficits and axon damage.
      METHODS: Amyloid-beta1-42 (Abeta1-42) was injected into the left lateral
      ventricle in mice. Two months after the injection, in vivo DTI and visual evoked
      potential (VEP) recordings were performed, followed by immunohistochemistry of
      phosphorylated neurofilament and myelin basic protein. RESULTS: DTI of Abeta1-42
      treated mice showed a significant increase of radial diffusivity in white matter
      including the optic nerves and tracts. The abnormality was associated with
      decreased amplitude and increased latency of VEP. Immunohistochemistry confirmed
      a significant loss of axons and myelin integrity. CONCLUSION: White matter damage
      induced by Abeta1-42 in mice can be detected non-invasively by DTI.

PMID- 24077433
TI  - Genetic interactions within inositol-related pathways are associated with
      longitudinal changes in ventricle size.
AB  - The genetic etiology of late-onset Alzheimer's disease (LOAD) has proven complex,
      involving clinical and genetic heterogeneity and gene-gene interactions. Recent
      genome wide association studies in LOAD have led to the discovery of novel
      genetic risk factors; however, the investigation of gene-gene interactions has
      been limited. Conventional genetic studies often use binary disease status as the
      primary phenotype, but for complex brain-based diseases, neuroimaging data can
      serve as quantitative endophenotypes that correlate with disease status and
      closely reflect pathological changes. In the Alzheimer's Disease Neuroimaging
      Initiative cohort, we tested for association of genetic interactions with
      longitudinal MRI measurements of the inferior lateral ventricles (ILVs), which
      have repeatedly shown a relationship to LOAD status and progression. We performed
      linear regression to evaluate the ability of pathway-derived SNP-SNP pairs to
      predict the slope of change in volume of the ILVs. After Bonferroni correction,
      we identified four significant interactions in the right ILV (RILV) corresponding
      to gene-gene pairs SYNJ2-PI4KA, PARD3-MYH2, PDE3A-ABHD12B, and OR2L13-PRKG1 and
      one significant interaction in the left ILV (LILV) corresponding to SYNJ2-PI4KA.
      The SNP-SNP interaction corresponding to SYNJ2-PI4KA was identical in the RILV
      and LILV and was the most significant interaction in each (RILV: p = 9.13 * 10(
      12); LILV: p = 8.17 * 10(-13)). Both genes belong to the inositol phosphate
      signaling pathway which has been previously associated with neurodegeneration in
      AD and we discuss the possibility that perturbation of this pathway results in a
      down-regulation of the Akt cell survival pathway and, thereby, decreased neuronal
      survival, as reflected by increased volume of the ventricles.

PMID- 24077435
TI  - Detecting the effect of Alzheimer's disease on everyday motion behavior.
AB  - BACKGROUND: Early detection of behavioral changes in Alzheimer's disease (AD)
      would help the design and implementation of specific interventions. OBJECTIVE:
      The target of our investigation was to establish a correlation between diagnosis
      and unconstrained motion behavior in subjects without major clinical behavior
      impairments. METHOD: We studied everyday motion behavior in 23 dyads with one
      partner suffering from AD dementia and one cognitively healthy partner in the
      subjects' home, employing ankle-mounted three-axes accelerometric sensors. We
      determined frequency features obtained from the signal envelopes computed by an
      envelope detector for the carrier band 0.5 Hz to 5 Hz. Based on these features,
      we employed quadratic discriminant analysis for building models discriminating
      between AD patients and healthy controls. RESULTS: After leave-one-out cross
      validation, the classification accuracy of motion features reached 91% and was
      superior to the classification accuracy based on the Cohen-Mansfield Agitation
      Inventory (CMAI). Motion features were significantly correlated with MMSE and
      CMAI scores. CONCLUSION: Our findings suggest that changes of everyday behavior
      are detectable in accelerometric behavior protocols even in the absence of major
      clinical behavioral impairments in AD.

PMID- 24077434
TI  - A randomized placebo-controlled pilot trial of omega-3 fatty acids and alpha
      lipoic acid in Alzheimer's disease.
AB  - Oxidative stress, inflammation, and increased cholesterol levels are all
      mechanisms that have been associated with Alzheimer's disease (AD) pathology.
      Several epidemiologic studies have reported a decreased risk of AD with fish
      consumption. This pilot study was designed to evaluate the effects of
      supplementation with omega-3 fatty acids alone (omega-3) or omega-3 plus alpha
      lipoic acid (omega-3 + LA) compared to placebo on oxidative stress biomarkers in
      AD. The primary outcome measure was peripheral F2-isoprostane levels (oxidative
      stress measure). Secondary outcome measures included performance on: Mini-Mental
      State Examination (MMSE), Activities of Daily Living/Instrumental Activities of
      Daily Living (ADL/IADL), and Alzheimer Disease Assessment Scale-cognitive
      subscale (ADAS-cog). Thirty-nine AD subjects were randomized to one of three
      groups: 1) placebo, 2) omega-3, or 3) omega-3 + LA for a treatment duration of 12
      months. Eighty seven percent (34/39) of the subjects completed the 12-month
      intervention. There was no difference between groups at 12 months in peripheral
      F2-isoprostane levels (p = 0.83). The omega-3 + LA and omega-3 were not
      significantly different than the placebo group in ADAS-cog (p = 0.98, p = 0.86)
      and in ADL (p = 0.15, p = 0.82). Compared to placebo, the omega-3 + LA showed
      less decline in MMSE (p < 0.01) and IADL (p = 0.01) and the omega-3 group showed
      less decline in IADL (p < 0.01). The combination of omega-3 + LA slowed cognitive
      and functional decline in AD over 12 months. Because the results were generated
      from a small sample size, further evaluation of the combination of omega-3 fatty
      acids plus alpha-lipoic acid as a potential treatment in AD is warranted. 

PMID- 24077436
TI  - Amyloid-beta alters the DNA methylation status of cell-fate genes in an
      Alzheimer's disease model.
AB  - Alzheimer's disease (AD) is characterized by neurofibrillary tangles and
      extracellular amyloid-beta plaques (Abeta). Despite ongoing research, some
      ambiguity remains surrounding the role of Abeta in the pathogenesis of this
      neurodegenerative disease. While several studies have focused on the mutations
      associated with AD, our understanding of the epigenetic contributions to the
      disease remains less clear. To that end, we determined the changes in DNA
      methylation in differentiated human neurons with and without Abeta treatment. DNA
      was isolated from neurons treated with Abeta or vehicle, and the two samples were
      digested with either a methylation-sensitive (HpaII) or a methylation-insensitive
      (MspI) restriction endonuclease. The fragments were amplified and co-hybridized
      to a commercial promoter microarray. Data analysis revealed a subset of genomic
      loci that shows a significant change in DNA methylation following Abeta treatment
      in comparison to the control group. After mapping these loci to nearby genes, we
      discovered high enrichment for cell-fate genes that control apoptosis and
      neuronal differentiation. Finally, we incorporated three of those genes in a
      possible model suggesting the means by which Abeta contributes to the brain
      shrinkage and memory loss seen in AD. 

PMID- 24077437
TI  - What is the main driver of ageing in long-lived winter honeybees: antioxidant
      enzymes, innate immunity, or vitellogenin?
AB  - To date five different theories compete in explaining the biological mechanisms
      of senescence or ageing in invertebrates. Physiological, genetical, and
      environmental mechanisms form the image of ageing in individuals and groups.
      Social insects, especially the honeybee Apis mellifera, present exceptional model
      systems to study developmentally related ageing. The extremely high phenotypic
      plasticity for life expectancy resulting from the female caste system provides a
      most useful system to study open questions with respect to ageing. Here, we used
      long-lived winter worker honeybees and measured transcriptional changes of 14
      antioxidative enzyme, immunity, and ageing-related (insulin/insulin-like growth
      factor signaling pathway) genes at two time points during hibernation.
      Additionally, worker bees were challenged with a bacterial infection to test
      ageing- and infection-associated immunity changes. Gene expression levels for
      each group of target genes revealed that ageing had a much higher impact than the
      bacterial challenge, notably for immunity-related genes. Antimicrobial peptide
      and antioxidative enzyme genes were significantly upregulated in aged worker
      honeybees independent of bacterial infections. The known ageing markers
      vitellogenin and IlP-1 were opposed regulated with decreasing vitellogenin levels
      during ageing. The increased antioxidative enzyme and antimicrobial peptide gene
      expression may contribute to a retardation of senescence in long-lived
      hibernating worker honeybees. 

PMID- 24077438
TI  - Effect of dexamethasone administered with magnesium sulfate on inflammation
      mediated degradation of the blood-brain barrier using an in vitro model.
AB  - Patients at risk for preterm delivery are frequently administered both antenatal
      steroids for fetal maturation and magnesium sulfate for neuroprotection. In this
      study, we investigate whether steroids coadministered with magnesium sulfate
      preserve blood-brain barrier integrity in neuroinflammation. Human umbilical vein
      endothelial cells were grown in astroglial conditioned media in a 2-chamber cell
      culture apparatus. Treatment with tumor necrosis factor-alpha (TNF-alpha) or
      catalytically active recombinant matrix metalloproteinase 9 (MMP-9) simulated
      neuroinflammation. Membrane integrity was assessed by zona occludens 1 (ZO-1)
      immunoreactivity, permeability to fluorescently conjugated dextran, and
      transendothelial electrical resistance (TEER). The TNF-alpha and MMP-9 treatment
      increased the rate of dextran transit, decreased TEER, and decreased ZO-1
      immunoreactivity at junctional interfaces. Dexamethasone pretreatment alone or in
      combination with 0.5 mmol/L magnesium sulfate preserved monolayer integrity after
      inflammatory insult. Magnesium sulfate alone was not protective. This study
      supports a possible interaction between steroids and magnesium in
      neuroprotection.

PMID- 24077440
TI  - The role of oxidative stress in the development of cisplatin resistance in
      epithelial ovarian cancer.
AB  - OBJECTIVE: To investigate the role of oxidative stress in the development of
      cisplatin resistance in epithelial ovarian cancer (EOC). METHODS: Two parent EOC
      cell lines (MDAH-2774 and SKOV-3) and their chemoresistant counterparts
      (cisplatin, 50 umol/L) were used. Total RNA was extracted and subjected to real
      time reverse transcriptase polymerase chain reaction to evaluate the expression
      of glutathione reductase (GSR) and inducible nitric oxide synthase (iNOS), as
      well as nitrate/nitrite levels. Analysis of variance was used for main effects
      and Tukey for post hoc analysis at P < .05 for statistical significance. RESULTS:
      Both cisplatin resistant cell lines displayed a significant decrease in GSR
      messenger RNA (mRNA) levels and activity (P < .01). As compared to sensitive
      controls, nitrate/nitrite levels were significantly higher in SKOV-3 cisplatin
      resistant cells while iNOS mRNA levels were significantly higher in MDAH-2774
      cisplatin resistant cells (P < .05). CONCLUSION: Our data suggest that the
      development of cisplatin resistance tilts the balance toward a pro-oxidant state
      in EOC.

PMID- 24077439
TI  - Developmental programming: postnatal estradiol amplifies ovarian follicular
      defects induced by fetal exposure to excess testosterone and dihydrotestosterone
      in sheep.
AB  - Excess of prenatal testosterone (T) induces reproductive defects including
      follicular persistence. Comparative studies with T and dihydrotestosterone (DHT)
      have suggested that follicular persistence is programmed via estrogenic actions
      of T. This study addresses the androgenic and estrogenic contributions in
      programming follicular persistence. Because humans are exposed to estrogenic
      environmental steroids from various sources throughout their life span and
      postnatal insults may also induce organizational and/or activational changes, we
      tested whether continuous postnatal exposure to estradiol (E) will amplify
      effects of prenatal steroids on ovarian function. Pregnant sheep were treated
      with T, DHT, E, or ED (E and DHT) from days 30 to 90 of gestation. Postnatally, a
      subset of the vehicle (C), T, and DHT females received an E implant. Transrectal
      ultrasonography was performed in the first breeding season during a synchronized
      cycle to monitor ovarian follicular dynamics. As expected, number of >=8 mm
      follicles was higher in the T versus C group. Postnatal E reduced the number of 4
      to 8 mm follicles in the DHT group. Percentage of females bearing luteinized
      follicles and the number of luteinized follicles differed among prenatal groups.
      Postnatal E increased the incidence of subluteal cycles in the prenatal T-treated
      females. Findings from this study confirm previous findings of divergences in
      programming effects of prenatal androgens and estrogens. They also indicate that
      some aspects of follicular dynamics are subject to postnatal modulation as well
      as support the existence of an extended organizational period or the need for a
      second insult to uncover the previously programmed event. 

PMID- 24077441
TI  - The pattern of tyrosine phosphorylation in human sperm in response to binding to
      zona pellucida or hyaluronic acid.
AB  - In mammalian species, acquisition of sperm fertilization competence is dependent
      on the phenomenon of sperm capacitation. One of the key elements of capacitation
      is protein tyrosine phosphorylation (TP) in various sperm membrane regions. In
      previous studies performed, the pattern of TP was examined in human sperm bound
      to zona pellucida of oocytes. In the present comparative study, TP patterns upon
      sperm binding to the zona pellucida or hyaluronic acid (HA) were investigated in
      spermatozoa arising from the same semen samples. Tyrosine phosphorylation,
      visualized by immunofluorescence, was localized within the acrosomal cap,
      equatorial head region, neck, and the principal piece. Tyrosine phosphorylation
      has increased in a time-related manner as capacitation progressed, and the
      phosphorylation pattern was identical within the principal piece and neck,
      regardless of the sperm bound to the zona pellucida or HA. Thus, the data
      demonstrated that the patterns of sperm activation-related TP were similar
      regardless of the spermatozoa bound to zona pellucida or HA. Further, sperm with
      incomplete development, as detected by excess cytoplasmic retention, failed to
      exhibit TP. 

PMID- 24077442
TI  - Luminol-based bioluminescence imaging of mouse mammary tumors.
AB  - Polymorphonuclear neutrophils (PMNs) are the most abundant circulating blood
      leukocytes. They are part of the innate immune system and provide a first line of
      defense by migrating toward areas of inflammation in response to chemical signals
      released from the site. Some solid tumors, such as breast cancer, also cause
      recruitment and activation of PMNs and release of myeloperoxidase. In this study,
      we demonstrate that administration of luminol to mice that have been transplanted
      with 4T1 mammary tumor cells permits the detection of myeloperoxidase activity,
      and consequently, the location of the tumor. Luminol allowed detection of
      activated PMNs only two days after cancer cell transplantation, even though
      tumors were not yet palpable. In conclusion, luminol-bioluminescence imaging
      (BLI) can provide a pathway towards detection of solid tumors at an early stage
      in preclinical tumor models. 

PMID- 24077443
TI  - Model studies of force-dependent kinetics of multi-barrier reactions.
AB  - According to transition state theory, the rate of a reaction that traverses
      multiple energy barriers is determined by the least stable (rate-determining)
      transition state. The preceding ('inner') energy barriers are kinetically
      'invisible' but mechanistically significant. Here we show experimentally and
      computationally that the reduction rate of organic disulphides by phosphines in
      water, which in the absence of force proceeds by an equilibrium formation of a
      thiophosphonium intermediate, measured as a function of force applied on the
      disulphide moiety yields a usefully accurate estimate of the height of the inner
      barrier. We apply varying stretching force to the disulphide by incorporating it
      into a series of increasingly strained macrocycles. This force accelerates the
      reduction, even though the strain-free rate-determining step is orthogonal to the
      pulling direction. The observed rate-force correlation is consistent with the
      simplest model of force-dependent kinetics of a multi-barrier reaction. 

PMID- 24077444
TI  - A method for non-experts in assessing exposure to risk factors for work-related
      musculoskeletal disorders--ERIN.
AB  - A practical method for non-experts in assessing exposure to risk factors for work
      related musculoskeletal disorders (WMSDs) is presented. Evaluacion del Riesgo
      Individual (Individual Risk Assessment) (ERIN) is based on available ergonomic
      tools, epidemiological evidence and the joint IEA-WHO project for developing
      WMSDs risk management in developing countries. ERIN focuses primarily on the
      interaction of some physical workplace factors but also includes the workers'
      assessment. A scoring system has been proposed to indicate the level of
      intervention required to reduce the risk of injury. A worksheet has also been
      designed for increasing the usability of the method. Preliminary tests show that
      it is easy and quick to use, but further work is needed to establish its
      reliability and validity. The use of ERIN can contribute to the prevention of
      WMSDs in Cuba and other developing countries. 

PMID- 24077445
TI  - Cost-benefit analysis of comprehensive mental health prevention programs in
      Japanese workplaces: a pilot study.
AB  - We examined the implementation of mental health prevention programs in Japanese
      workplaces and the costs and benefits. A cross-sectional survey targeting mental
      health program staff at 11 major companies was conducted. Questionnaires explored
      program implementation based on the guidelines of the Japanese Ministry of
      Health, Labor and Welfare. Labor, materials, outsourcing costs, overheads,
      employee mental discomfort, and absentee numbers, and work attendance were
      examined. Cost-benefit analyses were conducted from company perspectives
      assessing net benefits per employee and returns on investment. The surveyed
      companies employ an average of 1,169 workers. The implementation rate of the
      mental health prevention programs was 66% for primary, 51% for secondary, and 60%
      for tertiary programs. The program's average cost was 12,608 yen per employee and
      the total benefit was 19,530 yen per employee. The net benefit per employee was
      6,921 yen and the return on investment was in the range of 0.27-16.85. Seven of
      the 11 companies gained a net benefit from the mental health programs. 

PMID- 24077446
TI  - Analysis of construction accidents in Turkey and responsible parties.
AB  - Construction is one of the world's biggest industry that includes jobs as diverse
      as building, civil engineering, demolition, renovation, repair and maintenance.
      Construction workers are exposed to a wide variety of hazards. This study
      analyzes 1,117 expert witness reports which were submitted to criminal and labour
      courts. These reports are from all regions of the country and cover the period
      1972-2008. Accidents were classified by the consequence of the incident, time and
      main causes of the accident, construction type, occupation of the victim,
      activity at time of the accident and party responsible for the accident. Falls
      (54.1%), struck by thrown/falling object (12.9%), structural collapses (9.9%) and
      electrocutions (7.5%) rank first four places. The accidents were most likely
      between the hours 15:00 and 17:00 (22.6%), 10:00-12:00 (18.7%) and just after the
      lunchtime (9.9%). Additionally, the most common accidents were further divided
      into sub-types. Expert-witness assessments were used to identify the parties at
      fault and what acts of negligence typically lead to accidents. Nearly two thirds
      of the faulty and negligent acts are carried out by the employers and employees
      are responsible for almost one third of all cases. 

PMID- 24077448
TI  - Expert insights into the contemporary management of older adults with acute
      myeloid leukemia.

PMID- 24077447
TI  - The effects of impact vibration on peripheral blood vessels and nerves.
AB  - Research regarding the risk of developing hand-arm vibration syndrome after
      exposure to impact vibration has produced conflicting results. This study used an
      established animal model of vibration-induced dysfunction to determine how
      exposure to impact vibration affects peripheral blood vessels and nerves. The
      tails of male rats were exposed to a single bout of impact vibration (15 min
      exposure, at a dominant frequency of 30 Hz and an unweighted acceleration of
      approximately 345 m/s(2)) generated by a riveting hammer. Responsiveness of the
      ventral tail artery to adrenoreceptor-mediated vasoconstriction and acetylcholine
      mediated re-dilation was measured ex vivo. Ventral tail nerves and nerve endings
      in the skin were assessed using morphological and immunohistochemical techniques.
      Impact vibration did not alter vascular responsiveness to any factors or affect
      trunk nerves. However, 4 days following exposure there was an increase in protein
      gene product (PGP) 9.5 staining around hair follicles. A single exposure to
      impact vibration, with the exposure characteristics described above, affects
      peripheral nerves but not blood vessels. 

PMID- 24077449
TI  - Medium-term outcomes of cemented prostheses and cementless modular prostheses in
      revision total hip arthroplasty.
AB  - There is an increasing trend towards cementless modular femoral prostheses for
      revision hip replacement surgery, especially in patients with severe proximal
      femoral bone defects. However, for minor femoral bone defects, the benefit of
      cementless modular is not clear. We designed a retrospective cross-sectional
      study to compare outcomes of the two femoral implant designs. There were no
      significant differences in terms of visual analog pain scores, Harris hip scores,
      femoral bone restoration, stem subsidence, leg length correction, or overall
      complication rate. Three femoral reoperations (11%) occurred in the cemented
      group, and two (9%) in the cementless modular group. One femoral stem re-revised
      (4%) in the cemented group due to recurrent deep infection. Five-year survival
      for femoral reoperation was 88.2% for patients with the cemented implant and
      91.3% for cementless group. Both groups had good clinical and radiological
      outcomes for femoral revision in patients with minor femoral bone defects during
      medium-term follow-up. 

PMID- 24077450
TI  - Ferromagnetism and re-entrant spin-glass transition in quasicrystal approximants
      Au-SM-Gd (SM = Si, Ge).
AB  - Magnetic susceptibility and specific heat measurements on quasicrystalline
      approximants Au-Si-Gd and Au-Ge-Gd reveal that a ferromagnetic (FM) transition
      occurs at Tc = 22.5(5) K for Au-Si-Gd and at Tc = 13(1) K for Au-Ge-Gd, which are
      the first examples of ferromagnetism in crystalline approximants. In addition, a
      re-entrant spin-glass (RSG) transition is observed at TRSG = 3.3 K for Au-Ge-Gd
      in contrast to Au-Si-Gd. The different behaviors are understood based on the
      recent structural models reported by Gebresenbut et al (2013 J. Phys.: Condens.
      Matter 25 135402). The RSG transition in Au-Ge-Gd is attributed to a random
      occupation of the center of the Gd12 icosahedron by Gd atoms; a central Gd spin
      hinders the long-range FM order.

PMID- 24077451
TI  - Internet self-management uniform reporting framework: the need for uniform
      reporting criteria when reporting internet interventions.
AB  - A review of the literature was conducted to identify the "active ingredients"
      needed to produce successful Internet interventions that support older adults in
      self-management of chronic disease. The term "Internet intervention" was used as
      an umbrella term to include all online self-management programs. Thirteen
      articles were found to meet the inclusion criteria from the initial 204 articles
      identified. Ritterband's Model of Internet Interventions was used as a framework
      to classify the intervention components reported. It was found that online self
      management interventions can improve outcomes for some older adults. However, the
      wide diversity of interventions and the measures reported, coupled with the
      complex nature of the studies, made it difficult to identify the "active
      ingredients." To overcome this problem, the authors propose a minimum reporting
      set, the Internet Self-Management Uniform Reporting Framework, which can be used
      in the reporting of all interventions. Internet Self-Management Uniform Reporting
      Framework proposes the collection of specific data from six domains: Web site
      design, support, study design, Web site use, user characteristics and reporting
      outcomes. The adoption of Internet Self-Management Uniform Reporting Framework
      would enable easy comparison of online interventions targeting chronic diseases. 

PMID- 24077452
TI  - Health-related quality of life in patients with advanced nonsquamous non-small
      cell lung cancer receiving bevacizumab or bevacizumab-plus-pemetrexed maintenance
      therapy in AVAPERL (MO22089).
AB  - INTRODUCTION: In the phase III AVAPERL trial, patients with advanced nonsquamous
      non-small-cell lung cancer receiving bevacizumab-plus-pemetrexed maintenance
      after first-line induction had a significant progression-free survival benefit
      relative to those treated with single-agent bevacizumab maintenance but with an
      increase in grade >=3 adverse events. Here, we compare health-related quality of
      life (HRQOL) between AVAPERL maintenance arms. METHODS: Patient-reported outcomes
      were collected at designated intervals from preinduction to final visits. HRQOL
      was assessed using the self-administered European Organisation for Research and
      Treatment of Cancer Quality of Life Questionnaire Core 30 and the Quality of Life
      Lung Cancer-Specific Module 13. Differences in scores of 10 points or more
      between arms were above the minimum important difference threshold and considered
      clinically meaningful. RESULTS: During induction, patient-reported coughing
      symptoms improved slightly, whereas fatigue and appetite loss scores worsened
      relative to preinduction baseline. During maintenance, changes in mean global
      health status and the majority of Quality of Life Questionnaire Core 30 and
      Quality of Life Lung Cancer-Specific Module 13 subscale scores did not differ
      between trial arms by the minimum important difference defining clinically
      meaningful (better or worse) patient-reported outcomes. Exceptions were patient
      reported role functional status, fatigue symptoms and appetite loss symptoms
      (favoring bevacizumab), and pain in arm or shoulder symptoms (favoring
      bevacizumab-plus-pemetrexed maintenance), which differed by clinically meaningful
      amounts at more than one maintenance assessment. CONCLUSIONS: In AVAPERL, HRQOL
      remained relatively stable throughout maintenance and was generally similar in
      both arms. Despite an increase in adverse event rates, the addition of pemetrexed
      to bevacizumab maintenance resulted in similar stabilization of disease symptoms
      with improved efficacy outcomes.

PMID- 24077453
TI  - Transesophageal ultrasonography for lung cancer staging: learning curves of
      pulmonologists.
AB  - INTRODUCTION: Accurate mediastinal nodal staging is essential for patients with
      resectable non-small-cell lung cancer and is achieved by combined endobronchial
      ultrasound and transesophageal endoscopic ultrasound (EUS). Training requirements
      for EUS-guided fine-needle aspiration (FNA) for lung cancer staging are unknown.
      METHODS: Pulmonologists from Denmark and The Netherlands were enrolled in a
      dedicated, supervised training program. They performed standardized EUS-FNA
      procedures for mediastinal nodal analysis and their performances were assessed by
      EUS experts using a validated EUS assessment tool. Data were collected
      prospectively and used to plot learning curves and relate these to procedures
      performed by experienced investigators. RESULTS: Four participants performed 91
      EUS-FNA procedures (range, 19-24). The performances of the participants improved
      significantly and became more consistent, but were still highly variable even in
      the latter part of the learning curves. Only two of the participants reached the
      mean score of experienced operators-after 17 and 23 procedures, respectively.
      CONCLUSIONS: Pulmonologists with knowledge of lung cancer staging and experience
      in bronchoscopy quickly improved their performance of EUS-FNA. However,
      acquisition of skills varies between individuals, and certification should be
      based on assessment of performance of multiple cases. Twenty procedures were not
      enough to secure consistent and competent performance of all trainees.

PMID- 24077454
TI  - CDKN2A/p16 inactivation mechanisms and their relationship to smoke exposure and
      molecular features in non-small-cell lung cancer.
AB  - INTRODUCTION: CDKN2A (p16) inactivation is common in lung cancer and occurs via
      homozygous deletions, methylation of promoter region, or point mutations.
      Although p16 promoter methylation has been linked to KRAS mutation and smoking,
      the associations between p16 inactivation mechanisms and other common genetic
      mutations and smoking status are still controversial or unknown. METHODS: We
      determined all three p16 inactivation mechanisms with the use of multiple
      methodologies for genomic status, methylation, RNA, and protein expression, and
      correlated them with EGFR, KRAS, STK11 mutations and smoking status in 40 cell
      lines and 45 tumor samples of primary non-small-cell lung carcinoma. We also
      performed meta-analyses to investigate the impact of smoke exposure on p16
      inactivation. RESULTS: p16 inactivation was the major mechanism of RB pathway
      perturbation in non-small-cell lung carcinoma, with homozygous deletion being the
      most frequent method, followed by methylation and the rarer point mutations.
      Inactivating mechanisms were tightly correlated with loss of mRNA and protein
      expression. p16 inactivation occurred at comparable frequencies regardless of
      mutational status of EGFR, KRAS, and STK11, however, the major inactivation
      mechanism of p16 varied. p16 methylation was linked to KRAS mutation but was
      mutually exclusive with EGFR mutation. Cell lines and tumor samples demonstrated
      similar results. Our meta-analyses confirmed a modest positive association
      between p16 promoter methylation and smoking. CONCLUSION: Our results confirm
      that all the inactivation mechanisms are truly associated with loss of gene
      product and identify specific associations between p16 inactivation mechanisms
      and other genetic changes and smoking status.

PMID- 24077455
TI  - Prognostic value of fibroblast growth factor receptor 1 gene locus amplification
      in resected lung squamous cell carcinoma.
AB  - INTRODUCTION: Fibroblast growth factor receptor 1 (FGFR1) gene amplification was
      recently reported as a recurrent abnormality in 10% to 20% of primary lung
      squamous cell carcinomas (SqCCs), and has attracted significant interest as a
      potential therapeutic target. Limited data are available for its prognostic
      impact in early-stage SqCC. METHODS: Tissue microarrays containing 135 primary
      lung SqCCs and 58 matching lymph node metastases were tested by interphase
      fluorescence in situ hybridization for DNA copy number (CN) abnormalities at the
      8p12 region including FGFR1. RESULTS: FGFR1amplification was found in 18.2% (22
      of 121 evaluable) of primary SqCC, using a definition of average copies of FGFR1
      per cell of 5.0 or more. Concordance rate between primaries and matching lymph
      node metastases was 97.7% (43 of 44; 7 amplified and 37 nonamplified), with the
      only discordant case showing CN at approximately the dichotomous cutoff.
      Similarly, concordance between two separate lymph node metastases in each of 10
      patients was 100% (1 amplified and 9 nonamplified). Using various CN cutoffs, we
      found no statistically significant association between FGFR1 CN abnormalities and
      patient age, sex, tumor grade, stage, smoking status, disease-free survival,
      cause-specific survival, or overall survival. CONCLUSION: FGFR1 amplification is
      not prognostic in resected lung squamous cell carcinoma patients.

PMID- 24077457
TI  - Stereotactic body radiation therapy for primary lung cancers >3 centimeters.
AB  - INTRODUCTION: A retrospective analysis of the outcomes of stereotactic body
      radiation therapy (SBRT) in the treatment of large (>3 cm) non-small-cell lung
      cancers (NSCLCs). METHODS: Between February 2007 and November 2011, 63 patients
      with T2-T4N0 NSCLC were treated with SBRT. Toxicity was graded per Common
      Terminology Criteria for Adverse Events, version 4.0. Local failure-free survival
      (LFFS), recurrence-free survival, and overall survival curves were estimated
      using the Kaplan-Meier method and univariate analysis was performed using Cox
      regression. RESULTS: Median follow-up was 16.9 months. One- and 2-year LFFS was
      88.8% and 75.7%, 1- and 2-year recurrence-free survival was 59.0% and 41.6%, and
      1- and 2-year overall survival was 77.1% and 57.6%, respectively. Planning target
      volume less than 106 cm was associated with a significantly higher 1- and 2-year
      LFFS (p =0.05). Grade 2 or higher acute and late pulmonary toxicities occurred in
      19.3% and 19.3% of patients, respectively, and were not associated with common
      dose-volume parameters; 22.8% of patients developed grade 2 or higher chest wall
      pain, which was significantly associated with chest wall V30 70 cm or more (p =
      0.03). CONCLUSIONS: SBRT for larger NSCLC tumors achieves high LFFS with
      acceptable toxicity. LFFS was worse with planning target volume 106 cm or more.
      Grade 2 or higher chest wall pain was associated with chest wall V30 70 cm or
      more.

PMID- 24077456
TI  - Radioprotection of lung tissue by soy isoflavones.
AB  - INTRODUCTION: Radiation-induced pneumonitis and fibrosis have restricted
      radiotherapy for lung cancer. In a preclinical lung tumor model, soy isoflavones
      showed the potential to enhance radiation damage in tumor nodules and
      simultaneously protect normal lung from radiation injury. We have further
      dissected the role of soy isoflavones in the radioprotection of lung tissue.
      METHODS: Naive Balb/c mice were treated with oral soy isoflavones for 3 days
      before and up to 4 months after radiation. Radiation was administered to the left
      lung at 12 Gy. Mice were monitored for toxicity and breathing rates at 2, 3, and
      4 months after radiation. Lung tissues were processed for histology for in situ
      evaluation of response. RESULTS: Radiation caused damage to normal hair
      follicles, leading to hair loss in the irradiated left thoracic area.
      Supplementation with soy isoflavones protected mice against radiation-induced
      skin injury and hair loss. Lung irradiation also caused an increase in mouse
      breathing rate that was more pronounced by 4 months after radiation, probably
      because of the late effects of radiation-induced injury to normal lung tissue.
      However, this effect was mitigated by soy isoflavones. Histological examination
      of irradiated lungs revealed a chronic inflammatory infiltration involving
      alveoli and bronchioles and a progressive increase in fibrosis. These adverse
      effects of radiation were alleviated by soy isoflavones. CONCLUSION: Soy
      isoflavones given pre- and postradiation protected the lungs against adverse
      effects of radiation including skin injury, hair loss, increased breathing rates,
      inflammation, pneumonitis and fibrosis, providing evidence for a radioprotective
      effect of soy.

PMID- 24077458
TI  - Radiotherapy for postoperative thoracic lymph node recurrence of non-small-cell
      lung cancer provides better outcomes if the disease is asymptomatic and a single
      station involvement.
AB  - OBJECTIVE: Thoracic lymph node recurrence after complete resection is common in
      non-small-cell lung cancer but it mostly occurs along with distant metastases.
      The recurrent disease might be localized and curative intent radiation therapy is
      the treatment of choice if no evidence of hematogenous metastasis is observed. We
      sought to describe the outcomes of thoracic radiotherapy for thoracic lymph node
      recurrences. METHODS: Fifty patients who had developed thoracic lymph node
      recurrence after complete resection received curative intent radiotherapy between
      1997 and 2009. The clinical endpoints included the tumor response, overall
      survival, progression-free survival, locoregional recurrence within the
      irradiated field, and any other recurrence. RESULTS: The planned total
      radiotherapy was completed in 49 patients with minor toxicity. The median follow
      up time after radiotherapy was 41 (19-98) months among the survivors. The
      response to treatment was complete response in 65%, partial response in 24%, and
      progressive disease in 10% of the evaluated patients. The median overall survival
      after radiotherapy was 37.3 months. The 5-year overall survival, progression-free
      survival, and local control rate were 36.1%, 22.2%, and 61.1%, respectively. A
      multivariate analysis revealed that the absence of symptoms and the involvement
      of a single lymph node station were significant factors associated with a better
      overall survival. CONCLUSIONS: Radiation therapy for thoracic lymph node
      recurrence after complete resection is safe and provides acceptable disease
      control. This treatment provides a better outcome if the disease is asymptomatic
      and has a single-station involvement. Early detection of the recurrence may thus
      improve the effectiveness of this treatment.

PMID- 24077459
TI  - Radiotherapy for intubated patients with malignant airway obstruction: futile or
      facilitating extubation?
AB  - INTRODUCTION: The optimal approach to patients with malignant airway obstruction
      who require intubation and mechanical ventilation but are ineligible for
      bronchoscopic interventions is uncertain. Radiotherapy (RT) may be delivered but
      requires substantial resources in this patient population. In the absence of
      evidence, it is unknown whether RT facilitates extubation or delays an
      appropriate transition to end-of-life care. METHODS: We performed a 10-year
      retrospective review of intensive care unit (ICU) patients treated with RT while
      on mechanical ventilation for malignant airway obstruction. Primary study
      endpoints were overall survival (OS) and extubation success (ES), defined as 48
      hours or more without reintubation or death. Secondary endpoints included rates
      of discharge from the ICU and to home. Logistic regression and Cox regression
      analyses were performed to identify factors associated with OS and ES. RESULTS:
      Twenty-six patients were eligible for analysis. Seven patients (27%) were
      extubated; extubations occurred between days 4 and 22 after RT initiation. All
      patients were discharged from the ICU and most (n = 6) were also discharged home.
      An association between higher radiation doses and ES was observed (odds ratio per
      5 Gy increase: 0.63; p = 0.080). Median OS was only 0.36 months (range, 0-113
      months), and 6-month OS was 11%. On Cox regression analysis, increased radiation
      dose was predictive of improved OS (hazard ratio per 5 Gy increase: 0.74; p =
      0.016). CONCLUSIONS: A significant minority of patients receiving RT were
      successfully extubated. Higher radiation doses were predictive of improved OS and
      showed a trend for increased ES. Survival beyond 6 months was uncommon, however,
      the majority of patients with ES were able to be discharged home.

PMID- 24077461
TI  - Facile fabrication of novel highly microporous carbons with superior size
      selective adsorption and supercapacitance properties.
AB  - A facile approach to fabricate novel highly microporous carbons has been
      developed by direct carbonization of lowly cross-linked polystyrene. The as
      prepared highly microporous carbons demonstrate unusually high micropore rate
      (97%), high surface area (1108 m(2) g(-1)) and uniform pore size distribution,
      and thus exhibit excellent size-selective adsorption and electrochemical
      properties. 

PMID- 24077460
TI  - Development of a practical complete-kill assay to evaluate anti-Acanthamoeba
      drugs.
AB  - IMPORTANCE: Acanthamoeba keratitis is a debilitating eye disease that requires
      effective topical drug therapy. Currently, there is no standard in vitro test to
      evaluate anti-Acanthamoeba drugs. OBJECTIVE: To develop a practical in vitro
      complete-kill assay to assess anti-Acanthamoeba drugs. DESIGN AND SETTING:
      Isolates of Acanthamoeba strains (n = 15) evaluated in a clinical laboratory. An
      in vitro laboratory assay was created to determine whether polyhexamethylene
      biguanide, 0.02%, chlorhexidine digluconate, 0.02%, hexamidine diisethioonate,
      0.1%, and voriconazole, 1.0%, were effective in completely killing 15 different
      isolates of Acanthamoeba at time points of 24, 48, and 72 hours in comparison
      with a saline control. Each 0.5-mL volume of drug was inoculated with 0.1 mL of
      Acanthamoeba cysts (range, 1-3 * 10(6)/mL) (determined with a hemacytometer) and
      allowed to incubate at 30 degrees C. At the time points listed, 0.05 mL from each
      treatment group was inoculated onto nonnutrient agar overlaid with Enterobacter
      aerogenes. The plates were microscopically examined for growth 1 and 2 weeks
      after inoculation. At 2 weeks, all plates were subcultured onto a fresh medium.
      At another 7 days, the growth in subculture at each time point was graded "1" for
      growth and "0" for no growth. MAIN OUTCOMES AND MEASURES: The cumulative grades
      of 3 time points (range, 0-3) for each drug and isolate were nonparametrically
      compared to determine differences in growth between the drugs. The "kill"
      incidence rates over the 3 time points were also compared. RESULTS: In vitro
      testing determined that antiacanthamoebal efficacy (determined by the median
      growth grade and the kill incidence rate) was more prominent for hexamidine
      diisethioonate (median growth grade, 0.0; kill incidence rate, 93% [14 of 15
      isolates]) and polyhexamethylene biguanide (median growth grade, 0.0; kill
      incidence rate, 80% [12 of 15 isolates]) than for chlorhexidine digluconate
      (median growth grade, 1.0; kill incidence rate, 40% [6 of 15 isolates]),
      voriconazole (median growth grade, 2.0; kill incidence rate, 13% [2 of 15
      isolates]), and saline (median growth grade, 3.0; kill incidence rate, 0% [0 of
      15 isolates]). CONCLUSIONS AND RELEVANCE: The complete-kill assay appears to
      provide separation in the effectiveness of different antiamoebic drug solutions.
      This assay may be helpful for guiding topical Acanthamoeba therapy and providing
      a practical method to evaluate and screen new anti-infectives in the treatment of
      Acanthamoeba keratitis.

PMID- 24077462
TI  - Photophysics and electrochemistry of a platinum-acetylide disubstituted
      perylenediimide.
AB  - The synthesis and photophysical study of a perylene diimide (PDI) functionalised
      with platinum acetylide units of the type, trans{-C=C-Pt(PBu3)2-C=C-Ph} and
      comparison with a phenylacetylide substituted model compound are reported. The
      model compound demonstrates typical perylene absorption and photoluminescence
      spectra characteristic of singlet excited state formation and decay. The Pt
      substitution, however, appears to induce spin-orbit coupling into the chromophore
      and giving rise to a triplet excited state which was confirmed by transient
      absorption measurements. This excited state is quenched by oxygen, leading to the
      formation of singlet oxygen in dichloromethane, recorded by time-resolved near
      infrared luminescence measurements.

PMID- 24077463
TI  - Do young children spell words syllabically? Evidence from learners of Brazilian
      Portuguese.
AB  - The theory that learners of alphabetic writing systems go through a period during
      which they treat writing as representing syllables is highly influential,
      especially as applied to learners of Romance languages. The results of Study 1, a
      2-year longitudinal study of 76 Portuguese speakers in Brazil from 4 to 6 years
      of age, did not support this theory. Although most children produced some
      spellings of words in which the number of letters matched the number of
      syllables, few children produced significantly more such spellings than expected
      on the basis of chance. When such spellings did occur, they appeared to reflect
      partially successful attempts to represent phonemes rather than attempts to
      represent syllables. Study 2, with 68 Brazilian 4- and 5-year-olds, found similar
      results even when children spelled words that contained three or four syllables
      in which all vowels are letter names--conditions that have been thought to favor
      syllabic spelling. The influential theory that learners of Romance languages go
      through a period during which they use writing to represent the level of
      syllables appears to lack a solid empirical foundation.

PMID- 24077464
TI  - Attention to lexical stress and early vocabulary growth in 5-month-olds at risk
      for autism spectrum disorder.
AB  - Typically developing infants differentiate strong-weak (trochaic) and weak-strong
      (iambic) stress patterns by 2months of age. The ability to discriminate
      rhythmical patterns, such as lexical stress, has been argued to facilitate
      language development, suggesting that a difficulty in discriminating stress might
      affect early word learning as reflected in vocabulary size. Children with autism
      spectrum disorder (ASD) often have difficulty in correctly producing lexical
      stress, yet little is known about how they perceive it. The current study tested
      5-month-old infants with typically developing older siblings (SIBS-TD) and
      infants with an older sibling diagnosed with ASD (SIBS-A) on their ability to
      differentiate the trochaic and iambic stress patterns of the word form gaba. SIBS
      TD infants showed an increased interest in attention to the trochaic stress
      pattern, which was also positively correlated with vocabulary comprehension at
      12months of age. In contrast, SIBS-A infants attended equally to these stress
      patterns, although this was unrelated to later vocabulary size. 

PMID- 24077465
TI  - Young children's analogical problem solving: gaining insights from video
      displays.
AB  - This study examined how toddlers gain insights from source video displays and use
      the insights to solve analogous problems. The sample of 2- and 2.5-year-olds
      viewed a source video illustrating a problem-solving strategy and then attempted
      to solve analogous problems. Older, but not younger, toddlers extracted the
      problem-solving strategy depicted in the video and spontaneously transferred the
      strategy to solve isomorphic problems. Transfer by analogy from the video was
      evident only when the video illustrated the complete problem goal structure,
      including the character's intention and the action needed to achieve a goal. The
      same action isolated from the problem-solving context did not serve as an
      effective source analogue. These results illuminate the development of early
      representation and processes involved in analogical problem solving. Theoretical
      and educational implications are discussed. 

PMID- 24077466
TI  - Development of serial processing in reading and rapid naming.
AB  - Serial rapid automatized naming (RAN) is more strongly related to reading fluency
      than naming of isolated words, suggesting that the implementation of serial
      processing may underlie the RAN-reading relationship. In this study, 107 Greek
      children from Grade 2 and 107 from Grade 6 were tested with discrete and serial
      naming of digits, objects, and words in 50-item arrays. The correlation between
      discrete and serial word reading was very high in Grade 2 but only moderate in
      Grade 6. In confirmatory factor analysis, a reading-naming latent structure fit
      the Grade 2 data best; in contrast, a serial-discrete structure fit the Grade 6
      data. Thus, the superficial longitudinal stability of RAN-reading correlations
      belies vastly different patterns of interrelations, indicative of changes in the
      developing cognitive processes underlying both naming and reading. Word fluency
      tasks in Grade 2 are apparently accomplished largely as a series of isolated
      individual word naming trials even though multiple individual letters in each
      word may be processed in parallel. In contrast, specifically serial procedures
      are applied in Grade 6, presumably via simultaneous processing of multiple
      individual words at successive levels. It is proposed that this feat requires
      endogenous control of cognitive cascades. 

PMID- 24077467
TI  - Autism in children and correlates in Lebanon: a pilot case-control study.
AB  - BACKGROUND: Autism spectrum disorder (ASD) is a neurological disorder typically
      appearing before the age of three. The exact cause of autism remains uncertain,
      and several factors may be involved in its onset: genetic factors and possible
      environmental factors. The aim of this study was to assess the correlates of
      autism in the Lebanese population. METHODS: We investigated the association of
      autism with several factors in 86 autism cases from specialized schools for
      children with developmental disabilities and 172 control children from regular
      public schools in the same regions. Several risk factors for autism were
      investigated after comparison with a cohort control on parental age, sex,
      maternal unhappy feeling during pregnancy, consanguineous marriage, and province
      of residence. The Chi-square test was used to compare nominal variables, and
      Fisher exact test was used in case expected values within cells were inferior to
      five. For quantitative variables, we used t-test to compare means between two
      groups, after checking their distribution normality. For multivariate analysis,
      we used a forward stepwise likelihood ratio logistic regression. RESULTS: We
      observed male predominance (79.1%) among autistic infants. There was a
      significant association between autism and older parents age (OR=1.27), male sex
      (OR=3.38), unhappy maternal feeling during pregnancy (OR=5.77), living close to
      industry (OR=6.58), previous childhood infection (OR=8.85), but none concerning
      maternal age, paternal age and consanguinity. CONCLUSIONS: In this pilot
      epidemiological study of autism in Lebanon, we found several prenatal and
      perinatal risk factors for autism that could be modified.

PMID- 24077468
TI  - Prevalence and risk factors of urinary incontinence in women residing in a tribal
      area in Maharashtra, India.
AB  - BACKGROUND: To study the prevalence and risk factors of urinary incontinence in
      tribal women and to assess the treatment seeking behavior of affected women.
      METHODS: A cross-sectional descriptive study was conducted in Khardi, a tribal
      village, selected by random sampling, in Thane district, Maharashtra, India
      during the period October 2010 to January 2011. All women aged 20 years and above
      were selected for the study except pregnant and lactating women and those with
      neurological disorders affecting bladder continence. A semi-structured
      questionnaire assessing socio-demographic factors of women, severity, type of
      incontinence, obstetric and other risk factors of incontinence was administered
      to the study participants. The participants who suffered from incontinence were
      inquired regarding their treatment seeking behavior for the same. Logistic
      regression analysis was used to determine the independent association between
      these factors and primary outcome of incontinence. RESULTS: Of 353 women
      participated in the study, 90 (25.5%) reported urinary incontinence. Prevalence
      of urinary incontinence showed significant association with increasing age
      (P<0.010). Associated obstetric factors included high parity (P<0.001), early
      post-partum resumption of heavy work (P<0.050) and prolonged labor (P<0.010).
      Other risk factors like hypertension, diabetes, chronic cough and constipation
      were predictors of incontinence in regression analysis (R2=0.47). Healthcare
      seeking rate was only 14.4% since they either accepted incontinence as a normal
      ageing process or were embarrassed to seek medical advice. CONCLUSIONS: Urinary
      incontinence is a neglected problem in tribal women predicted by obstetric and
      other risk factors.

PMID- 24077469
TI  - Exposure to extremely low frequency electromagnetic fields during pregnancy and
      the risk of spontaneous abortion: a case-control study.
AB  - BACKGROUND: Exposure to extremely low frequency electromagnetic fields is
      increasingly common, but the potential influence on pregnant women has not been
      thoroughly investigated. METHODS: In this case-control study, 58 women who had an
      unexplained spontaneous abortion at < 14 weeks gestation and 58 matched pregnant
      women >14 weeks gestation were enrolled in 2012. The women completed the
      questionnaire, which was used to collect data about socioeconomic and obstetric
      characteristics, medical and reproductive histories. Then, to evaluate the
      extremely low frequency electromagnetic fields , we determined the magnitude of
      electromagnetic fields in the participants' houses by an exposure level tester
      (3D EMF tester/ Model: ELF-828; Taiwan).The instrument covers a limited frequency
      range (30 HZ to 3 KHZ). RESULTS: The magnitude of extremely low frequency
      electromagnetic fields in the participants' houses was significantly different
      between the two groups (P<0.001). CONCLUSIONS: Extremely low frequency
      electromagnetic fields exposure is probably related to early spontaneous
      abortions.

PMID- 24077470
TI  - Study on the performance of wet electroscrubber in purifying airborne particles.
AB  - BACKGROUND: In this study, an electroscrubber was designed and experimented for
      evaluation of integrating particle and droplet charging effects separately and
      jointly on collection efficiency of a spray tower and also to discover the
      optimal condition. METHODS: A homogenous concentration of relatively fine
      particles was introduced to influent air stream and electroscrubber efficiency in
      purifying them was determined through the measurement of input and output
      particles concentration. The effect of various conditions such as particles and
      droplets charging alone and together (bipolar) for several applied voltages has
      been studied. RESULTS: In all of experiments, the applied charging voltage has a
      key role in promotion of electroscrubber efficiency. Maximum collection
      efficiency has achieved for 15 Kilovolt (Kv). The effectiveness of bipolar
      charging of particles and droplets with 15 Kv was higher than that of no-charging
      and singly charging. In other words, efficiency can be increased from 84.43% to
      93.22 for total particles and from 50.8% to 75.16% for submicron particles. The
      maximum improvement of collection efficiency (42.2%) relates to bipolar charging
      of the initial size group with diameter smaller than 0.3 micrometer (um) and the
      minimum (0.5%) to sizing group of 11 with diameter 4-5 um. CONCLUSIONS: This
      approach can be an appropriate option for the purpose of purifying submicron
      particles in spray tower scrubbers.

PMID- 24077471
TI  - Social hidden groups size analyzing: application of count regression models for
      excess zeros.
AB  - BACKGROUND: In the case of sensitive questions such as number of alcoholics
      known, majority of respondents might give an answer of zero. Poisson regression
      model (P) is the standard tool to analyze count data. However, P provides poor
      fit in the case of zero inflated counts, when over-dispersion exists. Therefore,
      the questions to be addressed are to compare performance of alternative count
      regression models; and to investigate whether characteristics of respondents
      affect their responses. METHODS: A total of 700 participants were asked about
      number of people they know in hidden groups; alcoholics, methadone users, and
      Female Sex Workers (FSW). Five regression models were fitted to these outcomes:
      Logistic, P, Negative Binomial (NB), Zero Inflated Poisson (ZIP), and Zero
      Inflated Negative Binomial (ZINB). Models were compared in terms of Likelihood
      Ratio Test (LRT), Vuong, AIC and Sum Square of Error (SSE). RESULTS: Percentages
      of zero were 35% for number of alcoholics, 50% for methadone users, and 65% for
      FSWs. ZINB provided the best fit for alcoholics, and NB provided the best fit for
      other outcomes. In addition, we noticed that young respondents, male and those
      with low education were more likely to know or reveal sensitive information.
      CONCLUSIONS: Although P is the first choice for modeling of count data in many
      cases, it seems because of over-dispersion of zero inflated counts in the case of
      sensitive questions, other models, specifying NB and ZINB, might have better
      goodness of fit.

PMID- 24077473
TI  - Prevalence of overweight, obesity and central obesity among elementary school
      children in Birjand, east of Iran, 2012.
AB  - BACKGROUND: Prevalence of obesity in children has been increasing during recent
      decades all over the world. Obesity, particularly central obesity, is associated
      with metabolic syndrome and cardiovascular diseases. The present study aimed to
      assess obesity and central obesity in 6-11 year old Birjand elementary school
      children, East of Iran. METHODS: This cross-sectional study was conducted on 1541
      elementary school children, i.e. 851 girls and 690 boys, selected from Birjand
      elementary schools through multiple-cluster sampling in 2012. In order to
      determine overweight and obesity the percentile of CDC was used, so that, 85-95th
      percentile were taken as overweight and >95th percentile was defined as obese
      with respect to age and sex. For determination of central obesity, waist
      circumference and the >=90th percentile were used regarding age and sex. The
      obtained data was analyzed by means of SPSS software (V: 15) using t and chi
      square statistical tests at the 0.05 significant level. RESULTS: Out of the
      studied children, 9.6% (11% of boys and 8.3% of girls) were overweight and 9.2%
      of children (i.e. 10.9% of boys and 7.9% of girls) were obese. About 15.7% of
      children (i.e. 20.3% of boys and 12% of girls) had central obesity. CONCLUSIONS:
      Regarding high prevalence of obesity, central obesity, and overweight in Birjand
      elementary school children, it is recommended that families should be provided
      with necessary information with respect to correcting life-style and preventing
      obesity in children.

PMID- 24077472
TI  - Risk factors of congenital hypothyroidism using propensity score: a matched case
      control study.
AB  - BACKGROUND: The aim of this study was to investigate the relationship between
      congenital hypothyroidism and several variables using two different adjustment
      methods. METHODS: This matched case-control study was conducted in Hamadan
      Province, the west of Iran, in 2012 enrolling neonates born between 2005 and 2011
      and covered by screening program for congenital hypothyroidism. The neonates with
      TSH titer more than 10 mU/l or T4 titer less than 6.4 MUg/dl were considered as
      cases. Each case was individually matched for birth place and year with four
      neonates with normal TSH and T4 titers as controls. The data were analyzed using
      two different approaches including propensity score and multiple conditional
      logistic regression model. RESULTS: Of 1313 enrolled neonates, 277 (159 girls)
      were cases and 1036 (531 girls) were controls. The most important prognostic
      factors which had significant effect on congenital hypothyroidism included twin,
      birth season, maturity, jaundice at birth, birth weight, age at pregnancy,
      maternal anemia and goiter, gestational age, delivery type, father's education
      and smoking status, and consanguinity. The associations reported by logistic
      regression were stronger that of than propensity score analysis in most items,
      although the differences were not statistically significant. CONCLUSIONS: We
      addressed the effect of numerous potential risk factors on congenital
      hypothyroiditis and the impact of these factors on the disease occurrence.
      However, future prospective studies are needed to test these findings and
      hypothesis and to investigate the true effect of these potential risk factors on
      congenital hypothyroiditis.

PMID- 24077474
TI  - High prevalence of multidrug resistance and metallo-beta-lactamase (MbetaL)
      producing Acinetobacter baumannii isolated from patients in ICU wards, Hamadan,
      Iran.
AB  - BACKGROUND: Acinetobacter baumannii is gram- negative opportunistic coccobacilli,
      the most important agent in nosocomial infections with high mortality rate.
      Multidrug resistance in strains isolated from nosocomial infections, making it
      difficult to treat and sometimes impossible. The aim of the present study was to
      investigate antibiotic resistance in A. baumannii isolates from Iranian patients
      in Hamadan, west of Iran. METHODS: In this cross sectional study 100 A. baumannii
      isolated from trachea, blood, urine, sputum and wound samples of patients
      bedridden in Intensive care unit (ICU) wards of three educational hospitals
      during June 2011 to October 2012 was included. Isolates confirmed at species
      level using biochemical tests and tracing blaOXA-51 gene using Polymerase chain
      reaction (PCR) and preserved frozen at -70  degrees C until examination. Their
      susceptibility to 17 antibiotics was performed using Kirby-Bauer disc diffusion
      method. Determination of minimum inhibitory concentration and Metallo-beta
      lactamase production was carried out using E-test method. RESULTS: Resistance
      rate of isolates were 94%, 85%, 84%, 97%, 95% and 98% against meropenem,
      imipenem, amikacin, ciprofloxacin, piperacillin/tazobactam and cefotaxime,
      respectively. No resistant isolate was observed against tigecycline and also no
      sensitive isolate seen against aztreonam and cefotaxime. Results of E-test
      illustrated that 99% of all isolates were Metallo-beta-lactamase (MbetaL)
      producing, which were resistance to imipenem; also 85% of them were resistance to
      meropenem. MIC50 and MIC90 of the isolates were >=256 and >=32 mg/ml for imipenem
      and meropenem, respectively. CONCLUSIONS: The antibiotic resistance against most
      of the antibiotics, especially carbapenems is very high in Hamadan region. In
      addition colistin sulfate and tigecycline were most effective antibiotics and to
      be used in A. baumannii infections.

PMID- 24077475
TI  - Modeling the relationship between physical activity and quality of life in
      menopausal-aged women: a cross-sectional study.
AB  - BACKGROUND: The purpose of the present study was (a) to assess the relationship
      between physical activity and the intensity and duration of menopausal symptoms,
      (b) to investigate the relationship between physical activity and the four
      domains of health-related quality of life (HRQOL) and (c) to assess the
      relationship between physical activity and chronic diseases. METHODS: This
      descriptive-analytical study that was conducted in Tabriz City, Iran. Data were
      collected in 2012 by personal home-based interviews, using structured
      questionnaires. All participants (n= 273), who were middle-aged (age range of 40
      60 yr) were recruited from two of the 25 urban health service centers' clients,
      by clustered random sampling allocation. RESULTS: There was a positive
      significant relationship between Psychological, Social, and Environmental domains
      of HRQOL with physical activity (P<0.001). In addition, a negative significant
      relation was found between somatic complaints including sexual problems (P<
      0.017) and vaginal dryness (P<0.030) as well as joint-muscular discomfort
      (P<0.018), and the level of physical activity. Diabetic (P<0.047) and women with
      history of heart disease (P<0.040) performed 2.670 and 3.548 hours more than who
      were not. CONCLUSIONS: Regular physical activity would be effective in decreasing
      menopausal symptoms as well as improving healthy aging and also physical activity
      promotion as a part of healthy life style promotion programs needs to be improved
      in communities where women are physically inactive. In addition, women need to be
      informed about importance of physical activity on their life which it leads to
      feel healthy aging and pre and post- menopausal stages.

PMID- 24077476
TI  - Pediculosis capitis and relevant factors in secondary school students of Hamadan,
      west of Iran.
AB  - BACKGROUND: Pediculosis capitis is a problem in children and has worldwide
      distribution. The aim of the present study was to determine the prevalence of
      pediculosis degree and its relevant factors in the secondary schools in Hamadan
      west of Iran. METHODS: The study was carried out in two phases. A cross-sectional
      procedure was used to determine the prevalence of pediculosis, and the case study
      was done to identify the relevant factors to the infestation. Totally, 10841
      secondary students were chosen and classified in accordance with the clustering
      sample. RESULTS: The prevalence of pediculosis was 1.05%. It was 1.27% among the
      urban student; whereas 0.05% among the rural students. About 2.3% belonged to
      female students, and 0.11% was pertained to the male students. The greatest
      amount of infestation prevalence was reported from the schools of urban areas
      particularly in the public schools of suburbia. Furthermore, the prevalence of
      infestation was more where some individuals had pediculosis previous history and
      suffered from head inching. It turned out to be a significant relationship
      between pediculosis, head itching (P<0.001) and previous history of pediculosis
      (P<0.001). CONCLUSIONS: The prevalence of pediculosis in Hamadan is low, but is
      more in the areas which are deprived of the access to health facilities.
      Therefore, there is a need for educational campaigns about danger of infection
      and regular mass screening at school.

PMID- 24077477
TI  - Risk assessment of vapor cloud explosions in a hydrogen production facility with
      consequence modeling.
AB  - BACKGROUND: New technologies using hazardous materials usually have certain
      risks. It is more serious when the technology is supposed to be applied in a
      large scale and become widely used by many people. The objective of this paper
      was to evaluate the risk of vapor cloud explosion in a hydrogen production
      process. METHODS: Potential hazards were identified using the conventional hazard
      identification method (HAZID). The frequency of the proposed scenarios was
      estimated from statistical data and existing records. The PHAST professional
      software was applied for consequence modeling. Both individual and societal risks
      were evaluated. This cross-sectional study was conducted from June 2010 to
      December 2011 in a Hydrogen Production Plant in Tehran. RESULTS: The full bore
      rupture in heat exchanger had the highest harm effect distance. The full bore
      rupture in desulphurization reactor had the highest (57% of total) individual
      risk. Full bore rupture in heat exchanger was the highest contributor to social
      risk. It carried 64% & 66.7% of total risk in day and night respectively.
      CONCLUSIONS: For the sake of safety, mitigation measures should be implemented on
      heat exchanger, reformer and hydrogen purification absorbers. The main proposed
      risk reductive measures included; the increasing of installed equipment
      elevation, the application of smaller vessels and pipes.

PMID- 24077478
TI  - Treatment of waste sludge: a comparison between anodic oxidation and electro
      Fenton processes.
AB  - BACKGROUND: Electrochemical methods, as one of the advanced oxidation processes
      (AOPs), have recently been applied to remove different contaminants from water
      and wastewater. This study compares the performance of anodic oxidation (AO) and
      electro-Fenton (EF) methods on waste sludge treatment. METHODS: This experimental
      study was performed on real sludge and the effect of operating parameters such as
      solution pH, operating time, current density, supporting electrolyte and hydrogen
      peroxide concentration were investigated in a batch reactor. For determination of
      oxidation and treatability of the sludge, chemical oxygen demand (COD) and total
      coliform (TC) removal were examined. Pb/PbO2 and iron electrodes respectively for
      AO and EF were applied. RESULTS: Experimental data indicated for both AO and EF
      as the operating time and current density increased, COD removal increased.
      pH=4.0 and 3.0 and current density=1.75 and 2 A respectively for AO  and EF and
      the concentration = 57.2 mMol of hydrogen peroxide for EF were measured as the
      optimum amounts of these variables. The removal efficiency of COD in AO and EF
      process was 76% and 72%, respectively. Of course, the efficiency of EF in TC
      removal was better and the percentage of TC removal in 60 min for AO and EF was
      99.0% and 99.9%, respectively. The amounts of consumed electrical energy for AO
      and EF were 8.6 and 28.0 kWh kg-1 COD, respectively. CONCLUSIONS: AO was more
      effective in treatment and mineralization of waste sludge and TC removal than EF
      in terms of environmental economical features.

PMID- 24077479
TI  - The status of diabetes control in Kurdistan province, west of Iran.
AB  - BACKGROUND: Based on some estimation more than two million peoples in Iran are
      affected by Type 2 diabetes. The present study was designed to evaluate the
      status of diabetes control among Type 2 diabetes patients in Kurdistan, west of
      Iran and its associated factors. METHODS: In our cross sectional study conducted
      in 2010, 411 Type 2 diabetes patients were randomly recruited from Sanandaj,
      Capital of Kurdistan. Chi square test was used in univariate analysis to address
      the association between HgAlc and FBS status and other variables. The significant
      results from Univariate analysis were entered in multivariate analysis and
      multinomial logistic regression model. RESULTS: In 38% of patients, FBS was in
      normal range (70-130) and in 47% HgA1c was <7% which is normal range for HgA1c.
      In univariate analysis, FBS level was associated with educational levels
      (P=0.001), referral style (P=0.001), referral time (P=0.009), and insulin
      injection (P=0.016). In addition, HgA1c had a relationship with sex (P=0.023),
      age (P=0.035), education (P=0.001), referral style (P=0.001), and insulin
      injection (P=0.008). After using multinomial logistic regression for significant
      results of univariate analysis, it was found that FBS was significantly
      associated with referral style. In addition HgA1c was significantly associated
      with referral style and Insulin injection. CONCLUSIONS: Although some of patients
      were under the coverage of specialized cares, but their diabetes were not
      properly controlled.

PMID- 24077481
TI  - Cognitive processes and functions in patients with type 2 diabetes in comparison
      to pre-diabetic patients.
AB  - BACKGROUND: Type 2 diabetes is an important risk factor for cognitive decline in
      diabetic patients. The main goal of this study was the assessment of memory,
      attention and visuospatial ability dysfunctions in patients with type 2 diabetes
      in comparison to pre-diabetic patients and normal subjects in Endocrine and
      Metabolism Center of Isfahan City from April 2011 to July 2011. METHODS: The
      sample comprised of 32 patients with type 2 diabetes, 28 pre-diabetic patients
      and 30 healthy individuals. Memory, attention and visuospatial ability were
      assessed by Rey Complex Figure Test (RCFT), Paced Auditory Serial Addition Test
      (PASAT) and sub tests of Wechsler Adult Intelligence Scale-revised (WAIS-R).
      RESULTS: The pair wise comparisons of cognitive functions among three groups,
      suggesting a significant difference between diabetic and normal groups in
      PASAT3". PASAT2", RCFT (recall trial) and Symbol coding (P=0.003, P=0.009,
      P=0.010, and P<0.001, respectively). But there was no difference in copy trial of
      RCFT and block design between two groups (P=0.170, P=0.490). There was
      significant difference between pre-diabetic group and normal group in recall
      trial of RCFT (P=0.020), as well as significant difference between diabetes type
      2 and pre-diabetic group in symbol coding (P=0.001). CONCLUSIONS: There were
      significant differences in cognitive functions in patient with type2 diabetes,
      pre-diabetic patients and normal individuals. Thus monitoring neuropsychological
      status besides controlling levels of blood sugar in these patients is important.

PMID- 24077480
TI  - Noise annoyance due to construction worksites.
AB  - BACKGROUND: Noise pollution can contribute to adverse health effects in humans.
      Noise annoyance and related problems, caused by noise emission during the
      progress of building construction, have become increasingly important. These
      problems can influence the exposed workers, as well as vicinity residents. The
      goal of the present study was to assess the noise annoyance due to noise from
      construction worksites among residents of Hamadan City (west of Iran). METHODS:
      In this cross-sectional study, 20 construction worksites and 140 near vicinity
      residents were selected. The main sources of construction worksite noise were
      diesel power generators, cutting and welding processes, heavy machinery (such as
      trucks) and transport of materials. Ambient noise levels were measured using a
      calibrated sound level meter, at each home of the residents included in the
      study. A noise annoyance questionnaire was employed for annoyance assessment.
      RESULTS: The majority of subjects had very high annoyance (87.1%). The mean and
      SD of ambient levels were 74.57+/-7.12 dB (A) which exceeded the acceptable
      recommended level for residential areas. The most common problems among the
      participants were disturbance in sleep, difficulty in reading and distraction.
      Results showed significant relationship between noise annoyance and some factors
      including residing which floors had highest annoyance (F=13.22, P<0.001) and
      ambient noise (F=11.313, P<0.001). CONCLUSIONS: High levels of noise annoyance
      among near vicinity residents who are affected by construction activities. This
      means that construction activities and other noise related sources should be
      regarded as the major source of ambient noise leading to noise annoyance.

PMID- 24077482
TI  - Carbon nanotubes functionalized with fibroblast growth factor accelerate
      proliferation of bone marrow-derived stromal cells and bone formation.
AB  - Multi-walled carbon nanotubes (MWCNTs) were functionalized with fibroblast growth
      factor (FGF) and the advantages of their use as scaffolds for bone augmentation
      were evaluated in vitro and in vivo. The activity of FGF was assessed by
      measuring the effect on the proliferation of rat bone marrow stromal cells
      (RBMSCs). The presence of FGF enhanced the proliferation of RBMSCs and the FGF
      covalently conjugated to the nanotubes (FGF-CNT) showed the same effect as FGF
      alone. In addition, FGF-CNT coated sponges were implanted between the parietal
      bone and the periosteum of rats and the formation of new bone was investigated.
      At day 14 after implantation, a larger amount of newly formed bone was clearly
      observed in most pores of FGF-CNT coated sponges. These findings indicated that
      MWCNTs accelerated new bone formation in response to FGF, as well as the
      integration of particles into new bone during its formation. Scaffolds coated
      with FGF-CNT could be considered as promising novel substituting materials for
      bone regeneration in future tissue engineering applications. 

PMID- 24077483
TI  - Segmentation of brain magnetic resonance angiography images based on MAP-MRF with
      multi-pattern neighborhood system and approximation of regularization
      coefficient.
AB  - Existing maximum a posteriori probability and Markov random field (MRF) models
      have limitations associated with: (1) the ordinary neighborhood system being
      unable to differentiate subtle changes due to several-to-one correspondence
      within the neighborhood; and (2) difficulty finding an appropriate parameter to
      balance between the spatial context and the data likelihood. Aiming at overcoming
      the limitations and applications to segmentation of cerebral vessels from
      magnetic resonance angiography images, we have proposed (1) a multi-pattern
      neighborhood system and corresponding energy equation to enable the MRF model for
      segmenting fine cerebral vessels with complicated context; and (2) an iterative
      approximation algorithm based on the maximum pseudo-likelihood and the space
      coding mode for the automatic parameter estimation of high level model of MRF. In
      the implementation, two computational strategies have been employed to speed up:
      the candidate space of cerebral vessels based on a threshold of the response to
      multi-scale filtering, and parallel computation of major equations. Three
      phantoms simulating segmentation challenges of vessels have been devised to
      quantitatively validate the algorithm. In addition, 10 three-dimensional clinical
      data sets have been used to validate the algorithm qualitatively. It has been
      shown that the proposed method could yield smaller error, improve the spatial
      resolution of MRF model, and better balance the smoothing and data likelihood
      than the traditional trial-and-error estimation. Comparative studies have shown
      that the proposed method is better than the 3 segmentation algorithms (Hassouna
      et al., 2006; Hao et al., 2008; Gao et al., 2011) in terms of segmentation
      accuracy, robustness to noise and varying curvatures as well as radii. 

PMID- 24077485
TI  - Chlorobenzenes, lindane and dieldrin induce apoptotic alterations in human
      peripheral blood lymphocytes (in vitro study).
AB  - In this study, we have assessed apoptotic effect of 1,2,4-trichlorobenzene,
      hexachlorobenzene, lindane and dieldrin on human peripheral blood lymphocytes. We
      observed an increase in ROS formation and a decrease in mitochondrial
      transmembrane potential in the cells incubated with low concentrations of all
      compounds studied, in particular lindane and dieldrin. ROS formation and changes
      in mitochondrial transmembrane potential may have influenced caspase-3
      activation, a crucial enzyme in the apoptotic process. Moreover, chlorobenzenes,
      and in particular lindane and dieldrin changed cells' membrane permeability and
      induced phosphatidylserine translocation, which confirmed that they are capable
      of inducing apoptosis in human lymphocytes. Apoptotic changes in human
      lymphocytes provoked by biologically relevant concentrations of these substances
      suggest that they may disturb function of immunological system especially among
      people occupationally exposed to their action. 

PMID- 24077484
TI  - Brief hearing loss disrupts binaural integration during two early critical
      periods of auditory cortex development.
AB  - Early binaural experience can recalibrate central auditory circuits that support
      spatial hearing. However, it is not known how binaural integration matures
      shortly after hearing onset or whether various developmental stages are
      differentially impacted by disruptions of normal binaural experience. Here we
      induce a brief, reversible unilateral conductive hearing loss (CHL) at several
      experimentally determined milestones in mouse primary auditory cortex (A1)
      development and characterize its effects ~1 week after normal hearing is
      restored. We find that CHL shapes A1 binaural selectivity during two early
      critical periods. CHL before P16 disrupts the normal coregistration of interaural
      frequency tuning, whereas CHL on P16, but not before or after, disrupts
      interaural level difference sensitivity contained in long-latency spikes. These
      data highlight an evolving plasticity in the developing auditory cortex that may
      relate to the aetiology of amblyaudia, a binaural hearing impairment associated
      with bouts of otitis media during human infancy.

PMID- 24077486
TI  - [New knowledge from past decade: role of zinc in immune system].
AB  - Zinc (Zn) is essential for normal cell structure and physiology. Its deficiency
      causes growth retardation, neuronal degeneration, and immunodeficiency. Zn
      homeostasis is tightly controlled through Zn transporters and metallothioneins,
      which regulate Zn concentration and Zn distribution in individual cells, and
      contributes to Zn-binding protein in cells. Although many molecules involved in
      these processes have Zn-binding motifs, the molecular mechanisms underlying the
      role of Zn in the immune system have not been clarified. Recently, we and other
      groups have demonstrated that Zn plays diverse and specific roles in vivo and in
      vitro, in studies on the genetic knockout of Zn transporter functions. In this
      review, we discuss the impact of Zn on mast cell-mediated allergy and T cell
      mediated immune responses. We also describe Zn dysregulation as a leading health
      problem in allergy and immune responses. 

PMID- 24077487
TI  - [Principles and methods for vaccine epidemiology: evaluation of immunogenicity
      and effectiveness of pandemic H1N1 influenza vaccine].
AB  - Influenza vaccination is the most effective method of preventing influenza and
      its complications. In the 2009 influenza A (H1N1) pandemic, monovalent strain
      specific pandemic vaccines were developed rapidly. However, they were only
      available in limited supply at the initial stage of the vaccination campaign.
      Thus, tiered use of vaccines, after careful prioritization and determination of
      dose per individual, was important to maximize the benefit of the available
      doses. In this study, the principles and methods of epidemiological evaluation of
      influenza vaccines were investigated, focusing on the immunogenicity and
      effectiveness. The results of the study of the 2009/H1N1 pandemic will then be
      detailed. 

PMID- 24077488
TI  - [Comparison of data between intratracheal instillation and inhalation studies for
      estimation of harmful effects of manufactured nanomaterials].
AB  - We reviewed the difference in data between the inhalation and intratracheal
      instillation studies of inhaled materials and how to diminish the difference in
      data between the two studies in order to examine the usefulness of intratracheal
      instillation study for the estimation of the harmful effects of manufactured
      nanomaterials. The differences in the data of the intratracheal instillation
      study from those of the inhalation study, which is the gold standard, are as
      follows: 1) artificial effect of the bolus, 2) nonuniformity of lung distribution
      of materials, 3) no threshold of clearance, 4) low deposition level of materials
      in the brain and neonates, and 5) the effect of dispersant on the lung. We
      consider that the approaches to diminishing the difference in data between the
      two studies are as follows: 1) maintain the dispersion of nanomaterials, 2) avoid
      the overdosing of nanomaterials, and 3) maintain a low concentration of the
      dispersant in the intratracheal instillation study. 

PMID- 24077489
TI  - [National survey on eyelash extensions and their related health problems].
AB  - BACKGROUND: Eyelash extensions involve the attachment of synthetic eyelashes made
      of chemical fibers or other materials individually onto natural lashes. However,
      there are no uniform or well-established guidelines for this procedure.
      Consultations with ophthalmologists and local consumer centers regarding eyelash
      extension-related skin and eye disorders have been increasing yearly throughout
      Japan. This study was conducted to obtain epidemiologic data on eyelash
      extensions and their related health problems among the Japanese. METHODS: A web
      based survey was prepared and conducted with questions regarding the basic
      characteristics of the study participants, their experience with eyelash
      extensions (including the number of procedures, frequency of extension, year of
      first extension, and years since the first extension), and any extension-related
      health problems. Data from 2000 women, aged 15 to 59 years and randomly selected
      from across the country in accordance with the demographic composition of Japan,
      were included in the analysis. RESULTS: In total, 205 (10.3%) respondents
      reported having experienced eyelash extensions (average, 6.2 procedures; median,
      3.0), with a peak among those aged 25 to 29 years and a larger proportion of
      those living in urban areas than in rural areas. Of these women, 55 (26.8%)
      experienced health problems such as ocular hyperemia, pain, and itchy swollen
      eyelids. Multivariate analysis revealed that short intervals of extensions were
      associated with health problems (multiadjusted odds ratio (95% confidence
      interval); 2.88 (1.09-7.61)). CONCLUSIONS: Eyelash extensions are a popular
      procedure, especially among urban, young women. However, attention must be paid
      to the potential health risks of the procedure.

PMID- 24077490
TI  - [Physical and mental reactions to forest relaxation video--studies on gender
      differences].
AB  - OBJECTIVE: To explore gender differences in physical and mental relaxation in
      subjects who watched a forest relaxation video. METHODS: The subjects were 12
      males and 12 females in their 20's, with an average age of 21.67 +/- 1.00 and
      21.42 +/- 1.56, respectively. They rested for 5 minutes, and then watched either
      a forest relaxation video or control video (grey screen, no sound). After the
      video session, they rested again for 5 minutes. Thus, the total experimental
      duration was 20 minutes. Before and after the video session, subjects completed
      visual analog scales (VAS) on mood and Profile of Mood States (POMS)
      questionnaires. Subjects also pointed out the most comfortable scenes on the
      video. In addition, we measured their heart rates. Analyses were based on the
      semantic differential (SD) technique. RESULTS: The heart rate of male subjects
      decreased just after watching the relaxation video (p<0.05-0.01), and the LnHF
      increased (p<0.05-0.01), indicating significant activation of the parasympathetic
      nervous system. Regarding VAS scales, the "refreshment" score increased in male
      subjects (p<0.01). In females, all three scores for "pleasantness", "calmness",
      and "refreshment" increased after watching the relaxation video (p<0.05-0.001).
      In addition, the "tension-anxiety" score of the POMS decreased after watching the
      video (p<0.05). CONCLUSIONS: Both male and female subjects felt relaxed after the
      forest relaxation video. Especially, heart rate changes suggested that male
      subjects experienced relaxation after the video, whereas female subjects
      experienced mental relaxation.

PMID- 24077491
TI  - [Normative study of the Boston naming test in 7-year-old Japanese children].
AB  - OBJECTIVES: The Boston Naming Test (BNT) has been used to assess the language
      development of children in many epidemiology studies, and its usefulness is
      confirmed. The BNT consists of 60 black and white line drawings of objects and
      animals. There are no normative data available for this test for Japanese
      children. The purpose of this study was to collect normative information in Japan
      and to examine the correlation between the score of the BNT and Intelligence
      Quotient (IQ) of the Wechsler Intelligence Scale for Children third edition (WISC
      III). METHODS: The BNT was translated into Japanese and administered in children
      registered to the birth cohort of the Tohoku Study of Child Development at the
      age of 84 months. The participants for analysis in this study were 449 children
      (237 boys, 212 girls). RESULTS: There were four items with percentage scores
      below 1%; Igloo, Knocker, Muzzle, and Yoke. Many Japanese children could answer
      'abacus' and 'compass', which are difficult for US children. Although the score
      of the BNT correlated with IQ of the WISC-III (p<0.001), as compared with the
      previous studies, the correlation coefficient was low. CONCLUSIONS: The BNT is
      quick and easy to use and valuable for researchers in evaluating language ability
      in children. Since the BNT was developed in the United States, the cultural
      values of that country are reflected in the BNT score. This implies that the BNT
      should be modified to fit Japanese population.

PMID- 24077492
TI  - [Experience of weight loss and its related factors of thin females who still
      wished to lose weight among junior high school students].
AB  - OBJECTIVE: This study was aimed at clarifying the experience of weight loss and
      its related factors of thin females who still wished to lose weight among junior
      high school students. METHODS: The subjects were 1,302 males and females in the
      second and third grades in 17 junior high schools in A area in Wakayama
      Prefecture, Japan. The anonymous self-administered questionnaire included items
      on attributes, items relevant to weight loss, lifestyle, subjective symptoms, and
      items relevant to stress. A logistic regression analysis (likelihood ratio) was
      used with the question items showing a statistically significant difference when
      comparing the two groups as independent variables to identify the factors related
      to the experience of weight loss. RESULTS: There were 1,168 respondents (response
      rate, 89.7%). Eighty females who were less than -10% of the standard for obesity,
      but who still wished to lose weight, were selected from among 544 females. They
      were divided into two groups: those who had experienced losing weight (N=31,
      dieting group) and those who had never experienced losing weight (N=49,
      nondieting group). Between the two groups, there was a statistically significant
      difference in eight question items. The logistic regression analysis showed that
      believing oneself to be heavy by self-assessment, going to bed after midnight,
      and a short attention span were factors related to the experience of losing
      weight. CONCLUSION: Forty percent of the thin females who still wished to lose
      weight experienced weight loss. Distortion in the self-assessment of one's
      figure, inappropriate lifestyle, and subjective symptoms were designated as
      related factors.

PMID- 24077493
TI  - [Economic damage caused by lowered prices in the agro-food sector in areas
      contaminated by radioactive materials leaked from the nuclear power plant
      severely damaged by the 2011 Great East Japan Earthquake--consideration from the
      viewpoints of epidemiology, economics and social psychology].
AB  - INTRODUCTION: Large amounts of radioactive materials were leaked into the
      environment from the Fukushima Daiichi Nuclear Power Plant (FDNPP) of the Tokyo
      Electric Power Company, which was severely damaged by the 2011 Tohoku Region
      Pacific Coast Earthquake and accompanying tsunami. Economic damage due to lowered
      prices and supplies of food products produced in the areas contaminated by the
      radioactive materials leaked from the damaged FDNPP to the agro-food sector in
      the affected areas is notable. In Japanese, this is known as fuhyo higai. In this
      study, we investigated fuhyo higai from the viewpoints of epidemiology,
      economics, and social psychology in an effort to seek solutions. METHOD:
      Information was obtained from articles in print and on the Internet. RESULTS AND
      DISCUSSION: Fuhyo higai, or economic damage of the agro-food sector, which is the
      main industry in the contaminated areas, is serious because it is difficult to
      reassure the general population regarding food safety. This fuhyo higai does not
      derive solely from rumor. It has been reported that improving the science
      literacy of the general population is important as a countermeasure against fuhyo
      higai, but this may not be effective because of the human social structure and
      behavior of people who seek subjective safety. Almost all radiological laboratory
      results of samples of food produced in the contaminated areas were below
      detectable limits. Very high values were rarely detected. In general, information
      about the dose-response relationship is obtained under the assumption that there
      may be error in the response but not in the dose. The rare cases of extremely
      high radiological values of food samples from the contaminated areas may
      correspond to large errors in dose. However, it is difficult to deny a high-dose
      risk. The reported information on the dose-response relationship obtained under
      the assumption that there is no error in dose is not sufficient. Thus, response,
      i.e., health risk, cannot be correctly estimated. This leads the general
      population to choose food products from areas far from the FDNPP over those from
      the contaminated areas. In order to resolve this problem, thorough
      decontamination of radioactive areas, including large forests, is necessary for
      the market to regain competitiveness to the level it was before the accident. The
      cost of such decontamination is enormous and requires much labor. Decontamination
      will create employment and is indispensable in restoring the deteriorated
      economic conditions of the affected areas.

PMID- 24077496
TI  - [Editor's note].

PMID- 24077494
TI  - [In memory of Mr. Toru Takeuchi].

PMID- 24077497
TI  - Isolation and characterization of bioactive compounds from the bark of Litsea
      costalis.
AB  - The bark of Litsea costalis affords two new compounds named 4,4'-diallyl-5,5'
      dimethoxy-[1,1'-biphennyl]-2,2'-diol, biseugenol A (1) and 2,2'-oxybis (4-allyl-1
      methoxybenzene), biseugenol B (2) along with two known compounds (3-4), namely 5
      methoxy-2-Hydroxy Benzaldehyde (3), and (E)-4-styrylphenol (4). The structures of
      1 and 2 were determined using 1D and 2D NMR data. Also, the IR and NMR data were
      combined with quantum chemical calculations in the DFT approach using the hybrid
      B3LYP exchange-correlation function to confirm the structures of the compounds.
      Compounds showed fairly potent anticancer activity against cell lines and
      antioxidant (DPPH). 

PMID- 24077498
TI  - Risk factors for falls of older citizens.
AB  - OBJECTIVE: Fall prevention is a major issue in the ageing society. This study
      provides an overview of all risk factors for falls of older citizens. METHOD: A
      literature search was conducted to retrieve studies of the past 25 years. All
      participants from the studies lived in the community or institutions and were
      aged 60 or older. The following key word combinations were used, limited to the
      title: elderly or older people or older adults and fall and risk. The risk
      factors were categorised as relevant and amendable, relevant but non amendable,
      inconclusive or unsupported. RESULTS: In total 30 publications were studied in
      2013 in Enschede, the Netherlands. The relevant intrinsic risk factors are muscle
      strength, balance capacity, reactive power, dual tasking and sleep disturbance.
      Relevant extrinsic risk factors are home hazards, wrong use of assistive devices
      and bad footwear. Behaviour-related risk factors are hurrying, risk taking,
      physical inactivity and fear of falling. Relevant symptoms that could be caused
      by underlying risk factors are mobility problems, gait problems, vertigo, use of
      assisting devices and history of falls. CONCLUSIONS: Several risk factors are
      determined to be relevant and amendable. The provided overview could be used to
      create fall preventive measures for elderly.

PMID- 24077499
TI  - [Surgical treatment of patients with stomach cancer and severe concomitant cardio
      vascular pathology].
AB  - 51 patients with gastric cancer and severe concomitant ischemic heart disease
      (90.2%), valvular heart disease (5.9%), critical stenosis of the internal carotid
      artery (2%) or abdominal aortic aneurism (2%) were operated on during 1995
      2011yy. Of them men were 41, women - 10; mean age was 65.1 years (51-82). The
      first stage of gastric cancer was diagnosed in 18 (35.3%) of patients, second,
      third and fourth in 12 (23.5%), 17 (33.3%) and 4 (7.8%), respectively. Radical
      tumor resection was achieved in 37 (72.5%), palliative operations were performed
      in 13 (25.5%) patients. 17.6% of patients were operated on stomach and vessels
      simultaneously. 82.4% received the stepwise treatment. Intra- and postoperative
      complications were registered in 47.1% (24 of 51 patients); of whom 5.9% (3
      patients) ended lethally. Simultaneous operations showed the 55.6% complications
      and zero lethality rate, whereas stepwise treatment resulted in 45.2%
      complications and 7.1% lethality. 

PMID- 24077500
TI  - [The multifocal breast cancer].
AB  - Survival data of patients with multifocal breast cancer in dependence on surgical
      resection volume were analyzed. Two types of surgery were performed: the modified
      radical mastectomy by Madden and radical resection of the mammary gland. It was
      stated, that organ-preserving operation in combination with complex adjuvant
      therapy of the multifocal breast cancer stage I-II did not lead to the decrease
      of the overall and recurrence-free 5 and 10-year survival rate. 

PMID- 24077501
TI  - [The mithral valve replacement with biological prostheses: early and long-term
      results].
AB  - 442 patients underwent the mitral valve replacement (MVR) with KemCor and PeriCor
      stented bioprostheses. The study results justified the preference of the "totally
      biological" PeriCor valve in patients with active infectious endocarditis. The
      longest follow-up period was 11 years, the mean follow-up was 51+/-34 months. The
      risk of the structural valve disfunction was shown to be inversely proportional
      to the age (p=0.03). 38% of the operated women younger the 45, developed the
      structural valve disfunction in 79+/-27 months after surgery. Thus, MVR with
      stented bioprostheses proved to be clinically efficient early after the
      operation. Predictability of the results of KemCor and PeriCor valve implantation
      allows the theoretically substantiated approach to the rehabilitation,
      especially, considering the adverse event rate in different patient groups at
      certain follow-up periods. 

PMID- 24077502
TI  - [The quality of life after cholecystectomy].
AB  - The quality of life (QOL) of three groups of patients who had undergone the
      routine cholecystectomy (RCE), laparoscopic cholecystectomy (LCE), or
      cholecystectomy using the minilaparatomy approach (MCE). QOL was assessed using
      the standard SF-36 questionnaire and on selected criteria. The postoperative
      complications rate after any version of cholecystectomy did not exceed the
      average rate in other studies. Patients with a history of LCE and MCE, returned
      to their normal social and intellectual activity faster; they reported higher
      perception and judgment on the state of their health and well-being, which in
      turn suggests the higher quality of life. Patients after RCE reported worse
      results due to a longer recovery period. 

PMID- 24077503
TI  - [Early progressive organ failure in patients with severe acute pancreatitis].
AB  - The aim of the study was to investigate the role of early multiple organ failure
      in 152 patients with severe acute pancreatitis admitted to the intensive care
      unit for the period from 2002 to 2009. The group of patients with early
      progressive multiple organ failure had high early (29%) and overall mortality
      (45%) rate, infectious complications rate (39%) and long intensive care unit stay
      (median - 8 (5; 18) days). Based on the statistical analysis of data the criteria
      to predicted risk progression of multiple organ failure on admission were: APACHE
      II score >=12, SOFA score >=4, failure >2 organs/systems, Ranson score >=7. 

PMID- 24077504
TI  - [Results of the upper digestive tract stenting with self-expanding stents].
AB  - The work is based on the analysis of the palliative treatment of 66 patients with
      malignant upper digestive tract obstruction who underwent implantation of 75 self
      expanding metallic stents in the period of 2003-2012 yy. Early postoperative
      complications developed in 10 (15.2%) cases. Procedure-related complications were
      observed in 8 (12.1%) patients, non-specific complications occurred in 2 (3.0%)
      patients. In-hospital lethality was 4.5% (3 patients). 51 patients were followed
      until death. Symptomatic relapse of obstruction was observed in 4 cases. Median
      survival was 97 days. Stenting with self-expanding metal stents was concluded to
      be an effective and safe method of palliation of malignant upper digestive tract
      stenosis. 

PMID- 24077505
TI  - [The organ-preserving surgical treatment of the splenic rupture after the blunt
      abdominal trauma].
AB  - The outcomes of 383 cases of heavy combined traumas (n=273) and isolated (n=110)
      closed injuries of the abdomen with spleen damage were analyzed. The overall
      mortality was 11.74% (n=45), whereas the mortality rate during the first day
      after admission was 7.83% (n=30). Removal of a spleen was executed at 228
      patients. The spleen-preserving operation with ligation of splenic artery, was
      performed in 155 patients. The optimal level of the splenic artery ligation
      proved to be in its proximal and median parts. The postoperative CT-angiogarphy
      and Doppler US scanning together with the three-dimensional reconstruction
      confirmed that blood supply of the body and tail of the pancreas was satisfactory
      thanks to the natural collateral blood circulation. The dramatic decrease in
      lethality and of postoperative complication rates allows to consider spleen
      preserving resections to be a good alternative to spleenectomy. 

PMID- 24077507
TI  - [The differential choice of surgical modalities for the ventral postoperative
      hernia treatment].
AB  - The experience of 127 hernioplastics for postoperative ventral hernia using
      different methods during the period of 2000-2010 yy was analyzed. The algorithm
      for incisional ventral hernia has been worked out, considering the presence of
      recurrence risk factors and biochemical parameters. The results of treatment of
      18 patients, using the algorithm, showed no local and general postoperative
      complications, which allowed to consider it as the evidence of algorythm's
      effectiveness. 

PMID- 24077506
TI  - [Chemichal desympathization in the treatment of throphic ulcer in patients with
      varicose veins of the lower limbs].
AB  - The in vivo study on 25 rabbits and clinical study, involving 60 patients with
      lower limbs' varicose disease and trophic ulcers was carried out. The in-vivo
      study was based on the chemical distruction of the sympathic trunk by injecting
      95% ethanol and 6% phenol paraneurally along the vascular bundle in the ear. The
      regeneration of the sympathic neural trunk was registered within 2-3 months after
      the injury. In human patients the US-guided chemical desympathization led to the
      increase of the capillary circulation (1.9 times at rest and 0.3 times under the
      load) during 2 months. The fact favoured the faster regress of inflammatory
      process in the ulcer. 

PMID- 24077508
TI  - [Inhalation induction anesthesia: special indications or a routine procedure?].
AB  - The efficacy, safety and expediency of various types of the induction anesthesia
      before the long-lasting major surgery were analyzed. The combination of
      inhalation of sevoflurane in maximal concentration with phentanil allowed the
      effective and safe induction and trachea intubation on the 3-4th minute on the
      background of the nimbex myoplegia. The monoinduction with sevoflurane provides
      the sufficient analgesia not earlier then after 7-9th minute, which allows the
      safe intubation at a time. Therefore, the study proved, that the inhalation
      induction with sevoflurane in various modifications, could be the standard method
      of inductive anesthesia. 

PMID- 24077509
TI  - [Mesenterial by-pass in a female patient with multifocal atherosclerosis].

PMID- 24077510
TI  - [The duplicational gastric cyst in a 3 years old child].

PMID- 24077512
TI  - Fluorescence in-situ hybridization and dermoscopy in the assessment of
      controversial melanocytic tumors.
AB  - Although the 'gold standard' for melanoma diagnosis remains histopathological
      analysis, presently dermoscopists play a significant role in the diagnostic
      process. However, even a combined approach may not allow a clear-cut judgment on
      equivocal melanocytic lesions. Fluorescence in-situ hybridization (FISH) can
      offer assistance in the evaluation of chromosome abnormalities associated with
      malignancies, and its role is emerging in melanoma diagnosis. The aim of this
      study was to evaluate the diagnostic role of the FISH in the assessment of
      controversial lesions, defined as those lesions showing discrepancies between
      dermatoscopic and histological evaluations. Twenty clinically and histologically
      ambiguous melanocytic lesions were selected. After the first histopathologic
      diagnosis, a second pathologist examined the specimens in a blinded review for a
      second opinion and to identify the most suitable areas to hybridize using probes
      specific to RREB1, MYB, and CCND1 genes and the centromere of chromosome 6. The
      first histopathological evaluation led to the diagnosis of melanoma in seven
      cases, whereas the second identified eight cases of malignant melanoma and was in
      agreement with the first in 65% of cases and with dermoscopy in 40% of cases.
      Cytogenetic abnormalities detected by FISH are markers of malignancy that can be
      useful in the characterization of difficult-to-diagnose melanocytic tumors, when
      the dermatologist and the pathologist have a different opinions. 

PMID- 24077511
TI  - Chemoprevention of skin melanoma: facts and myths.
AB  - Melanoma is the most dangerous type of skin cancer. Despite the rise of public
      awareness, the incidence rate among the white population has been rising
      constantly for several decades. Systematic improvement in knowledge about the
      biology of pigment cells and molecular mechanisms of their neoplastic
      transformation has enhanced the possibility of melanoma chemoprevention. Hence,
      chemopreventive agents that prevent, inhibit, or reverse melanoma development are
      being investigated intensively. Among synthetic compounds, especially well
      studied are lipid-lowering drugs and cyclooxygenase inhibitors. Substances found
      in everyday diet, such as genistein, apigenin, quercetin, resveratrol, and
      curcumin may also have potential chemopreventive qualities. However, studies
      examining the chemopreventive activity of these compounds have shown widely
      varying results. Early reports on the possible chemopreventive activity of
      statins and fibrates were not proved by the results of randomized clinical
      trials. Similarly, case-control studies examining the influence of NSAIDs on the
      risk of melanoma do not confirm the antitumor activity of cyclooxygenase
      inhibitors. Further clinical trials involving carefully selected target
      populations as well as the identification of specific biomarkers of prognostic
      and predictive value seem to be essential for the evaluation of the
      chemopreventive activity of the studied substances. 

PMID- 24077513
TI  - [Service agreements vith Icelandic GP's--better service for the public
      [Editorial]].

PMID- 24077514
TI  - [Modernising when downsizing--opening a psychiatric intensive care unit at
      Landspitali [Editorial]].

PMID- 24077515
TI  - [Medication use in nursing homes in Iceland 2002-2004. A descriptive study].
AB  - PURPOSE: To describe medication use in nursing homes in Iceland during the years
      2002-2004. METHODS: In nursing homes using automated medication delivery, the
      number of medications used were calculated, from the beginning of 2002 to the end
      of 2004. Information was obtained from 10 nursing homes; a total of 1409
      individuals or approximately 60% of the inhabitants of all nursing homes in
      Iceland. 65% of the population were women, mean age was 83 years and 43% died
      during the study periond. The total number of prescribed medications was
      collected as well as their use for common chronic conditions and symptoms was
      analysed. RESULT: There were on average 8.9 (+/-4,0) medications used at the
      beginning of the study period, increasing to 9.9 (+/-4,3) by its end. On average,
      women got one more medication than men (p<0,001). 56.2% of women and 47% of men
      received >10 kinds of medication by the end of the study. Women got more
      psychiatric medications than men, but men got more medications for cardiovascular
      diseases. 82% of the population used psychiatric medications regularly, 65% used
      sedatives/hypnotics, 50% antidepressants and 20 % antipsychotics. Approximately
      additional 15% used psychiatric medication temporarily over the study period. The
      majority of medications were used constantly during the study period, especially
      cardiovascular medications. Medication for urinary incontinence, non steroidal
      antiinflammatory medications, medications for osteoporosis and medications
      against Alzheimers disease were used more often temporarily than constantly.
      Medications that were in constant use by >40% of the population were
      sedative/hypnotics, antidepressants, paracetamol, diuretics and vitamin D.
      CONCLUSION: There is a high number of medications used in nursing homes in
      Iceland. Most medications were already in use at the start of the study and
      continued throughout the study period indicating that medication review might be
      lacking. There are no indications of under-treated of pain or depression. Vitamin
      D is frequently used but should be used more often not least among men.

PMID- 24077516
TI  - [Spontaneus intracerebral haemhorrhage--review].
AB  - Spontaneous intracerebral hemorrhage occurs when a blood vessel within the brain
      parenchyma ruptures without a near related trauma. It is the second most common
      form of stroke, accounting for approximately 10% to 15% of new strokes. The 30
      day mortality is very high (25-50%). Hypertension is the most common cause.
      Unfortunately, surgery has not proven to be helpful except in certain exceptions
      such as in large cerebellar hemorrhage. Nonetheless, it is very important that
      patients with ICH are admitted to an intensive care or a stroke unit with close
      surveillance of consciousness, focal neurologic symptoms, blood pressure and
      fluid balance.

PMID- 24077518
TI  - From the Cross (and Crescent) to the Cedar and Back Again: Transnational Religion
      and Politics Among Lebanese Christians in Senegal.
AB  - This article examines the changing relationship between religion, secularism,
      national politics, and identity formation among Lebanese Christians in Senegal.
      Notre Dame du Liban, the first Lebanese religious institution in West Africa,
      draws on its Lebanese "national" character to accommodate Lebanese Maronite
      Catholic and Greek Orthodox Christians in Dakar, remaining an icon of "Lebanese"
      religion, yet departing from religious sectarianism in Lebanon. As such,
      transnational religion can vary from national religion, gaining new resonances
      and reinforcing a wider "secular" ethno-national identity.

PMID- 24077517
TI  - Cancer stem cells and therapeutic targets: an emerging field for cancer
      treatment.
AB  - Recent paradigm in the field of cancer defines its origin from a small population
      of fast growing cells known as cancer stem cells (CSCs), and they are mainly
      responsible for disease aggressiveness, drug resistance and tumor relapse. The
      existence of CSCs has been proven in different types of cancer and possesses
      characteristic expression of a wide array of cell surface markers specific to the
      type of cancer. CSCs have been isolated and enriched using several surface
      markers in different cancer types. Self-renewal, drug resistance and the ability
      to transition from epithelial to mesenchymal phenotype are the major features
      attributed to this fraction of mutated stem cells. The CSC hypothesis proposes
      that these CSCs mimic stem cells by sharing similar pathways, such as Wnt, SHH,
      Notch and others. Further, the niche, which in this case is the tumor
      microenvironment, plays a very important role in the maintenance of CSCs.
      Altogether, this emerging field of research on CSCs is expected to unveil answers
      to the most difficult issues of one of the most dreadful diseases called cancer. 

PMID- 24077520
TI  - Photoelectrocatalytic performance of a titania-keggin type polyoxometalate-gold
      nanocomposite modified electrode in methanol oxidation.
AB  - Aminosilicate sol-gel supported titania-keggin type polyoxometalate-gold
      nanocomposite materials (APS/(P25-PTA-Au)NCM) (APS, (3
      aminopropyl)triethoxysilane; P25, Degussa-TiO2; PTA, Na3PW12O40.xH2O) were
      prepared by a simple chemical reduction method and characterized by diffuse
      reflectance spectroscopy, photoluminescence, x-ray diffraction, transmission
      electron microscopy and energy-dispersive x-ray analysis. The as-prepared
      APS/(P25-PTA-Au)NCM was used to fabricate the photoelectrode for a
      photoelectrochemical cell. The photoelectrocatalytic activity of the APS/(P25-PTA
      Au)NCM modified photoelectrode in methanol oxidation was investigated. The
      APS/(P25-PTA-Au)NCM modified photoelectrode showed a higher photocurrent for
      methanol oxidation than control photoelectrodes. The modification of titania
      using PTA and Au nanoparticles significantly boosted the photoelectrocatalytic
      performance by a synergistic effect and thus improved the interfacial charge
      transfer processes. The presence of Au nanoparticles enhances the interfacial
      electron transfer process. The APS silicate sol-gel matrix acts as a very good
      support material for the preparation of the nanocomposite material and for
      preparation of the chemically modified electrode. This newly fabricated APS/(P25
      PTA-Au)NCM modified photoelectrode could be a promising candidate for
      photoelectrochemical cells.

PMID- 24077519
TI  - Thin-film tunable filters for hyperspectral fluorescence microscopy.
AB  - Hyperspectral imaging is a powerful tool that acquires data from many spectral
      bands, forming a contiguous spectrum. Hyperspectral imaging was originally
      developed for remote sensing applications; however, hyperspectral techniques have
      since been applied to biological fluorescence imaging applications, such as
      fluorescence microscopy and small animal fluorescence imaging. The spectral
      filtering method largely determines the sensitivity and specificity of any
      hyperspectral imaging system. There are several types of spectral filtering
      hardware available for microscopy systems, most commonly acousto-optic tunable
      filters (AOTFs) and liquid crystal tunable filters (LCTFs). These filtering
      technologies have advantages and disadvantages. Here, we present a novel tunable
      filter for hyperspectral imaging-the thin-film tunable filter (TFTF). The TFTF
      presents several advantages over AOTFs and LCTFs, most notably, a high percentage
      transmission and a high out-of-band optical density (OD). We present a comparison
      of a TFTF-based hyperspectral microscopy system and a commercially available AOTF
      based system. We have characterized the light transmission, wavelength
      calibration, and OD of both systems, and have then evaluated the capability of
      each system for discriminating between green fluorescent protein and highly
      autofluorescent lung tissue. Our results suggest that TFTFs are an alternative
      approach for hyperspectral filtering that offers improved transmission and out-of
      band blocking. These characteristics make TFTFs well suited for other biomedical
      imaging devices, such as ophthalmoscopes or endoscopes.

PMID- 24077521
TI  - Fluorescent light-up probe with aggregation-induced emission characteristics for
      in vivo imaging of cell apoptosis.
AB  - In this paper, a new live-cell permeable, fluorescent light-up probe comprised of
      a hydrophilic caspase-specific Asp-Glu-Val-Asp (DEVD) peptide and a hydrophobic
      tetraphenylethene pyridinium unit has been developed for in vivo cell apoptosis
      imaging and drug screening. The probe shows a specific light-up response to
      activated caspase-3/7 with a high signal-to-background ratio. The significant
      fluorescence turn-on response of the probe is due to the aggregation of cleaved
      hydrophobic residues that populate the radiative decay channels. With good water
      solubility and biocompatibility, the probe is demonstrated to be a promising
      candidate for in vivo real time monitoring of caspase activation and in situ
      screening of apoptosis-inducing drugs. 

PMID- 24077522
TI  - Multiple genetic origins of histidine-rich protein 2 gene deletion in Plasmodium
      falciparum parasites from Peru.
AB  - The majority of malaria rapid diagnostic tests (RDTs) detect Plasmodium
      falciparum histidine-rich protein 2 (PfHRP2), encoded by the pfhrp2 gene.
      Recently, P. falciparum isolates from Peru were found to lack pfhrp2 leading to
      false-negative RDT results. We hypothesized that pfhrp2-deleted parasites in Peru
      derived from a single genetic event. We evaluated the parasite population
      structure and pfhrp2 haplotype of samples collected between 1998 and 2005 using
      seven neutral and seven chromosome 8 microsatellite markers, respectively. Five
      distinct pfhrp2 haplotypes, corresponding to five neutral microsatellite-based
      clonal lineages, were detected in 1998-2001; pfhrp2 deletions occurred within
      four haplotypes. In 2003-2005, outcrossing among the parasite lineages resulted
      in eight population clusters that inherited the five pfhrp2 haplotypes seen
      previously and a new haplotype; pfhrp2 deletions occurred within four of these
      haplotypes. These findings indicate that the genetic origin of pfhrp2 deletion in
      Peru was not a single event, but likely occurred multiple times. 

PMID- 24077524
TI  - In vitro antimalarial activity, beta-haematin inhibition and structure-activity
      relationships in a series of quinoline triazoles.
AB  - A novel series of quinoline triazole amide analogues (38-51) has been
      synthesized. Analogues 38-44 had a Cl substituent at the 7-position of the
      quinoline ring, while 45-51 had a CN substituent at this position. Compounds 40,
      45 and 49 were found to be the most active in the series against the Plasmodium
      falciparum chloroquine-sensitive D10 strain, with IC50 values in the range of 349
      1247 nM, with 40 and 45, but not 49 also exhibiting similar activity against the
      chloroquine-resistant K1 strain of parasite. Quinoline triazoles 40 and 44 were
      the most active beta-haematin inhibitors, with 50% inhibitory concentrations of
      14.7 and 8.9 MUM respectively. In vitro antimalarial activity of the 7-Cl bearing
      analogues 38-44 exhibited a strong linear dependence of log(1/IC50) on log P.
      Thus, the more lipophilic, the more active it was found be. The 7-CN series 45-51
      showed no such dependence. The resistance index (IC50 K1/IC50 D10) also exhibited
      a linear dependence on log P, with a substantially steeper slope in the case of
      the 7-Cl series. The findings demonstrate the feasibility of producing
      hydrophilic analogues with strong activity and low cross-resistance with
      chloroquine.

PMID- 24077523
TI  - Stem Cells for Neurovascular Repair in Stroke.
AB  - Stem cells exert therapeutic effects against ischemic stroke via transplantation
      of exogenous stem cells or stimulation of endogenous stem cells within the
      neurogenic niches of subventricular zone and subgranular zone, or recruited from
      the bone marrow through peripheral circulation. In this paper, we review the
      different sources of stem cells that have been tested in animal models of stroke.
      In addition, we discuss specific mechanisms of action, in particular
      neurovascular repair by endothelial progenitor cells, as key translational
      research for advancing the clinical applications of stem cells for ischemic
      stroke.

PMID- 24077525
TI  - Synthesis, antibacterial and antioxidant activities of new 1-alkyl-4-(1-alkyl-4
      oxo-1,4-dihydroquinolin-2-yl)pyridinium bromides.
AB  - New 1-alkyl-4-(1-alkyl-4-oxo-1,4-dihydroquinolin-2-yl)pyridinium bromides (3a-k)
      were synthesized from 1,4'-diazaflavone [2-pyridin-4-ylquinolin-4(1H)-one] and
      evaluated for antibacterial and antioxidant activities. A rapid one-pot
      preparation of 1,4'-diazaflavone (2) was done from 2'-amino substituted chalcone
      (1) by intramolecular Michael addition using solvent-free microwave heating. New
      N,N'-dialkyl substituted (C5-C15) 1,4'-diazaflavonium bromides were synthesized
      from compound 2 with corresponding alkyl halides. Compounds 3a-k were active
      against six bacteria (MIC: 7.8-500.0 MUg/mL). They also showed good antioxidant
      activities in DPPH scavenging (SC50: 45-133 MUg/mL) and ferric
      reducing/antioxidant power (14-141 MUM TEAC) tests. The biological activities
      decreased as alkyl chain length increased. The reason behind the obvious negative
      effect of alkyl chain elongation is unclear and requires investigations about the
      intermolecular interactions of these pyridinium salts with bioassay components.

PMID- 24077526
TI  - Development of 3-phenyl-4,5,6,7-tetrahydro-1H-pyrazolo[4,3-c]pyridine derivatives
      as novel Mycobacterium tuberculosis pantothenate synthetase inhibitors.
AB  - Forty 3-phenyl-4,5,6,7-tetrahydro-1H-pyrazolo[4,3-c]pyridine derivatives were
      synthesized from piperidin-4-one by five step synthesis and evaluated for
      Mycobacterium tuberculosis (MTB) pantothenate synthetase (PS) inhibition study,
      in vitro activities against MTB, cytotoxicity against RAW 264.7 cell line. Among
      the compounds, 1-benzoyl-N-(4-nitrophenyl)-3-phenyl-6,7-dihydro-1H-pyrazolo[4,3
      c]pyridine-5(4H)-carboxamide (6ac) was found to be the most active compound with
      IC50 of 21.8 +/- 0.8 MUM against MTB PS, inhibited MTB with MIC of 26.7 MUM and
      it was non-cytotoxic at 50 MUM.

PMID- 24077527
TI  - Squaric acid/4-aminoquinoline conjugates: novel potent antiplasmodial agents.
AB  - We report the synthesis and structure-activity relationship (SAR) analysis of a
      series of hybrid compounds containing a squaric moiety conjugated with
      heterocyclic moieties from well-known antimalarials. This novel series of
      compounds presents improved antiplasmodial activity compared with the squaric
      derivatives described in our previous work. Three compounds, 8b (IC50 = 99 nM),
      8c (IC50 = 95 nM), and 8d (IC50 = 105 nM) had greater in vitro potency than
      chloroquine 1 (IC50 = 140 nM) against chloroquine resistant Plasmodium
      falciparum. In addition, they were noncytotoxic against NIH 3T3 and Hek 293T
      cells.

PMID- 24077528
TI  - Synthesis and anticancer activity of some novel trifluoromethylquinolines
      carrying a biologically active benzenesulfonamide moiety.
AB  - Several trifluoromethylquinoline derivatives containing a biologically active
      benzenesulfonamide moiety 2-14, 16, urea derivatives 15, 17, 4-isothiocyanate 18
      and the corresponding carbamimidothioic acid derivatives 19-30, were synthesized
      from the strategic starting material 4-chloro-7-trifluoromethylquinoline 1. The
      structures of the newly synthesized compounds were elucidated on the basis of
      elemental and spectral analyses. All the prepared compounds were evaluated for
      their in vitro anticancer activity against various cancer cell lines. Most of the
      synthesized compounds showed good activity, especially compound 15 which
      exhibited higher activity than the reference drug doxorubicin. In order to
      suggest the mechanism of action for their cytotoxic activity, molecular docking
      for all synthesized compounds was done on the active site of PI3K and good
      results were obtained.

PMID- 24077530
TI  - Activity profile relationships between structurally similar promiscuous
      compounds.
AB  - Compound promiscuity results from specific interactions of a small molecule with
      multiple biological targets and is an emerging concept in medicinal chemistry and
      drug discovery as it provides the basis for polypharmacology. Recent studies have
      assessed the degree of promiscuity among drugs and bioactive compounds. On the
      basis of currently available data, many drugs and bioactive compounds have been
      found to interact with more than one target. Herein, we further extend the study
      of promiscuity by focusing on structurally similar promiscuous compounds,
      comparing their activity profiles, and determining multi-target activity
      patterns. The analysis revealed that most structurally similar promiscuous
      compounds have identical or similar activity profiles but also detected different
      types of structure-activity pattern relationships. In addition, the propensity of
      activity cliff formation among promiscuous compounds was determined. Activity
      cliffs were formed at a high rate among promiscuous compounds indicating that
      many structurally similar promiscuous compounds have greatly varying activity
      against one or more targets they share. Taken together, these findings show that
      compound promiscuity and target selectivity are not mutually exclusive and
      further refine current views of promiscuity. 

PMID- 24077531
TI  - On the edge: the clinician-scientist in ophthalmology.

PMID- 24077529
TI  - Design, synthesis and efficacy of novel G protein-coupled receptor kinase 2
      inhibitors.
AB  - G protein-coupled receptor kinase 2 (GRK2) is a relevant signaling node of the
      cellular transduction network, playing major roles in the physiology of various
      organs/tissues including the heart and blood vessels. Emerging evidence suggests
      that GRK2 is up regulated in pathological situations such as heart failure,
      hypertrophy and hypertension, and its inhibition offers a potential therapeutic
      solution to these diseases. We explored the GRK2 inhibitory activity of a library
      of cyclic peptides derived from the HJ loop of G protein-coupled receptor kinases
      2 (GRK2). The design of these cyclic compounds was based on the conformation of
      the HJ loop within the X-ray structure of GRK2. One of these compounds, the
      cyclic peptide 7, inhibited potently and selectively the GRK2 activity, being
      more active than its linear precursor. In a cellular system, this peptide
      confirms the beneficial signaling properties of a potent GRK2 inhibitor.
      Preferred conformations of the most potent analog were investigated by NMR
      spectroscopy. 

PMID- 24077532
TI  - Chiral heterobimetallic complexes targeting human DNA-topoisomerase Ialpha.
AB  - The chiral monometallic Cu(II) (1) and Zn(II) (2) and heterobimetallic Cu(II)
      Sn(IV) and Zn(II)-Sn(IV) complexes with tridentate chiral Schiff base -ONO-ligand
      in the presence of nitrogen donor heterocyclic ligand imidazole; were prepared
      and characterized by various physico-chemical and spectroscopic methods.
      Preliminary complex-DNA interaction studies employing optical methods revealed
      that 3 displayed a higher propensity towards the drug target DNA double helix and
      recommended predominantly an electrostatic mode of interaction as well as a
      groove binding affinity of the complex with CT-DNA. This was quantified by Kb and
      KSV values of complexes 1-4, which demonstrated a multifold increase in complex 3
      binding to CT DNA and clearly demonstrates its potency to act as a
      chemotherapeutic agent. Furthermore, the gel electrophoretic patterns of
      supercoiled pBR322 DNA with varying concentrations of complex 3 exhibits the
      ability to cleave DNA and follow a freely diffusible radical mechanism. The
      antiproliferative effects of complex 3 on human hepatoma cancer cells (Huh7) was
      investigated. Human Topo I inhibition assay by complex 3 was performed and
      results confirmed significantly good activity at lower concentrations than some
      of the classical Topo I inhibitors. Additionally, complex 3 was investigated for
      the expression of MMP-2 and TGF-beta by real time PCR. The cellular uptake of
      complex 3 by HeLa cells was studied by confocal microscopy. 

PMID- 24077533
TI  - Demonstration of a novel focusing small-angle neutron scattering instrument
      equipped with axisymmetric mirrors.
AB  - Small-angle neutron scattering (SANS) is the most significant neutron technique
      in terms of impact on science and engineering. However, the basic design of SANS
      facilities has not changed since the technique's inception about 40 years ago, as
      all SANS instruments, save a few, are still designed as pinhole cameras. Here we
      demonstrate a novel concept for a SANS instrument based on axisymmetric focusing
      mirrors. We build and test a small prototype, which shows a performance
      comparable to that of conventional large SANS facilities. By using a detector
      with 48-MUm pixels, we build the most compact SANS instrument in the world. This
      work, together with the recent demonstration that such mirrors could increase the
      signal rate at least 50-fold, for large samples, while improving resolution,
      paves the way to novel SANS instruments, thus affecting a broad community of
      scientists and engineers.

PMID- 24077535
TI  - Integrated management strategies for tomato Fusarium wilt.
AB  - Fusarium wilt is caused by the fungal pathogens, Fusarium oxysporum or Fusarium
      solani. It is a devastating disease that affects many important food and
      vegetable crops and a major source of loss to farmers worldwide. Initial
      strategies developed to combat this devastating plant disease include the use of
      cultural, physical and chemical control. None of these strategies have been able
      to give the best results of completely ameliorating the situation except for the
      cultural method which is mainly preventive. A good knowledge of the nature,
      behaviour and environmental conditions of growth of the disease agent is very
      important to controlling the disease development in that case. Biological control
      has been shown to be an environmentally friendly alternative. It makes use of
      rhizospheric and endophytic microorganisms that can survive and compete
      favourably well with the Fusarium wilt pathogen. They include plant growth
      promoting rhizobacteria (PGPR) such as Bacillus spp. and Pseudomonas spp. For
      PGPR to control or inhibit the growth of the Fusarium wilt pathogen, they make
      use of mechanisms such as indole acetic acid production, siderophore production,
      phosphate solublilization, systemic resistance induction and antifungal volatile
      production among others.

PMID- 24077536
TI  - Synergistic effect of proanthocyanidin on the bactericidal action of the
      photolysis of H2O2.
AB  - The in vitro antibacterial activity of the hydroxyl radical generation system by
      the photolysis of H2O2 in combination with proanthocyanidin, which refers to a
      group of polyphenolic compounds, was examined. Bactericidal activity of photo
      irradiated H2O2 at 405 nm against Streptococcus mutans, a major pathogen of
      dental caries, was augmented in the presence of proanthocyanidin, whose
      bactericidal effect by itself was very poor, in a concentration-dependent manner.
      This combination was also proven effective against Porphyromonas gingivalis, a
      major pathogen of periodontitis. It is speculated that H2O2, generated from photo
      irradiated proanthocyanidin around the bacterial cells, is photolyzed to the
      hydroxyl radical, which would in turn affect the membrane structure and function
      of the bacterial cells, resulting in augmented sensitivity of bacterial cells to
      the disinfection system utilizing the photolysis of H2O2. The present study
      suggests that the combination of H2O2 and proanthocyanidin works synergistically
      to kill bacteria when photo-irradiated. 

PMID- 24077537
TI  - Phenol-oxidizing enzyme expression in Lentinula edodes by the addition of sawdust
      extract, aromatic compounds, or copper in liquid culture media.
AB  - This study examined how the addition of a sawdust extract from Castanopsis
      cuspidata, several aromatic compounds, and copper affected the expression of a
      phenol-oxidizing enzyme in the white-rot basidiomycete, Lentinula edodes.
      Compared to liquid media that had not been supplemented with sawdust extract
      (MYPG), MYPG containing low (MYPG-S100) or high (MYPG-S500) concentrations of
      sawdust extract had a marked effect on the promotion of mycelial growth. No
      manganese peroxidase (MnP) production was observed in either MYPG or MYPG-S100
      media until 35 days after inoculation. However, MnP production was enhanced by
      culture in MYPG-S500, with a marked increase observed suddenly at 14 days after
      inoculation. Northern blot analysis revealed that the transcription of the lemnp2
      gene coding extracellular MnP was initially observed at detectable levels at day
      10 after the initial inoculation of MYPG-S500, increasing gradually thereafter
      until days 22-25. However, laccase (Lcc) production was not observed in any of
      the media until 35 days after inoculation. Addition of 10 mM aromatic compounds -
      1,2-benzenediol, 2-methoxyphenol, hydroquinone, and 4-anisidine--into the MYPG
      S500 medium completely inhibited MnP production and did not enhance any Lcc
      production. While the addition of 1 or 2 mM Cu2+ (CuSO4 x 5H2O) to MYPG-S500
      medium completely inhibited MnP production, this Cu2+ addition caused a marked
      increase in Lcc production at 17 and 6 days after the addition, respectively.

PMID- 24077538
TI  - Antimicrobial activity of the carnivorous plant Dionaea muscipula against food
      related pathogenic and putrefactive bacteria.
AB  - Solvent extracts from the carnivorous plant Dionaea muscipula (Venus flytrap)
      were prepared using eight different organic solvents, and examined for
      antibacterial activity against food-related pathogenic and putrefactive bacteria.
      All solvent extracts showed higher antibacterial activity against gram positive
      bacteria than against gram negative bacteria. The TLC-bioautography analysis of
      the extracts revealed that a yellow spot was detected at Rf value of 0.85, which
      showed strong antibacterial activity. The UV, MS, and NMR analyses revealed that
      the antibacterial compound was plumbagin.

PMID- 24077539
TI  - Evaluation of immunochromatography for the rapid and specific identification of
      Listeria monocytogenes from food.
AB  - To rapidly, simply and specifically detect and identify Listeria monocytogenes
      from food samples, an immunochromatographic assay, based on gold-labeled
      monoclonal antibodies directed against an antigen common to all serovars of L.
      monocytogenes, was used. All strains of L. monocytogenes serovars showed a
      positive reaction to the assay, but all other gram positive and negative bacteria
      did not. The detection limit of the assay was in the order of 10(6) cfu/ml in
      fluid medium. The assay could simply and rapidly identify L. monocytogenes within
      30 min by a pure culture without special instruments. Even if the selective
      enrichment cultivation was employed for the isolation and growth of bacteria from
      food materials, the application of the assay system could detect and identify L.
      monocytogenes precisely in various food materials within 2 to 3 days. 

PMID- 24077541
TI  - Isolation of Legionella species from Noyu (unattended natural hot springs in
      mountains and fields) samples in Japan.
AB  - In order to understand the habitation conditions of the bacteria of the genus
      Legionella in Noyu (unattended natural hot springs in mountains and fields) in
      Japan, isolation of Legionella spp. was attempted in the Noyu samples from 11
      prefectures nationwide between May and September 2012, and the following results
      were obtained. Overall, Legionella spp. was isolated from 16 of 43 samples
      (37.2%). The species was isolated from the Hokkaido region to the Chugoku region
      but not from the Shikoku region to the Kyushu region. The number of bacteria
      detected was usually small, less than 5.0 * 10(1) CFU/100 ml, as found in 11
      samples (68.8%), while counts of 10(2) or more to 10(3) or less CFU/100 ml were
      found in two samples (12.5%). Legionella pneumophila was the most commonly found
      strain, with 19 strains (90.5%) found, and was the dominant species. Regarding
      the serogrouping, four strains (21.1%) fell under group 1, the most common
      grouping, followed by three strains (15.8%) in group 3, two strains (10.5%) in
      group 5, etc. Moreover, the detected bacterial strains other than L. pneumophila
      included two strains (9.5%) of L. londiniensis. The temperature of the Noyu from
      which Legionella spp. was isolated was between 33.1 degrees C and 41.5 degrees C
      with a pH ranging from 5.2 to 8.1. The present report is the first report to
      clarify the habitation conditions of strains of Legionella spp. isolated from
      Noyu in Japan.

PMID- 24077540
TI  - Antimicrobial activity of isothiocyanates (ITCs) extracted from horseradish
      (Armoracia rusticana) root against oral microorganisms.
AB  - The antimicrobial activity of isothiocyanates (ITCs) extracted from horseradish
      root was investigated against oral microorganisms: 6 strains of facultative
      anaerobic bacteria, Streptococcus mutans, Streptococcus sobrinus, Lactobacillus
      casei, Staphylococcus aureus, Enterococcus faecalis and Aggregatibacter
      actinomycetemcomitans; one strain of yeast, Candida albicans, and 3 strains of
      anaerobic bacteria, Fusobacterium nucleatum, Prevotella nigrescens, and
      Clostridium perfringens. The ITCs extracted from horseradish root showed
      antimicrobial activity against all oral microorganisms by the paper disk method.
      The minimum bactericidal concentration (MBC) of the ITCs extracted from
      horseradish root ranged from 1.25 to 5.00 mg/ml against 6 strains of facultative
      anaerobic bacteria and one strain of yeast, and 4.17 to 16.67 mg/ml against 3
      strains of anaerobic bacteria. The ITCs extracted from horseradish root showed
      the strongest antimicrobial activity, with a MBC of 1.25 mg/ml, against C.
      albicans among facultative microorganisms, and 4.17 mg/ml against F. nucleatum
      among anaerobic bacteria. These results suggest that the ITCs extracted from
      horseradish root may be a candidate for use as an antimicrobial agent against
      oral microorganisms.

PMID- 24077542
TI  - Development of a predictive program for Salmonella enteritidis growth in ground
      chicken and liquid egg products.
AB  - In this study, we developed a predictive program for Salmonella Enteritidis
      growth in ground chicken and liquid egg products at various temperature patterns.
      The ground chicken samples were sterilized chicken and raw chicken containing
      high and low levels of natural microflora, and the liquid egg products were
      pasteurized or unpasteurized. Microbial growth data published in our previous
      papers were used for prediction with our new logistic model. The program for the
      bacterial growth in those food materials was developed on a commercially
      available spread-sheet program. Users can instantly predict the Salmonella growth
      in those chicken and egg yolk products by inputting their temperature histories.
      The growth of natural microflora in the chicken products can also be predicted
      with the program. This program could be a useful tool to ensure the microbial
      safety of those materials with regards to Salmonella Enteritidis growth.

PMID- 24077543
TI  - Heuristic-based tabu search algorithm for folding two-dimensional AB off-lattice
      model proteins.
AB  - The protein structure prediction problem is a classical NP hard problem in
      bioinformatics. The lack of an effective global optimization method is the key
      obstacle in solving this problem. As one of the global optimization algorithms,
      tabu search (TS) algorithm has been successfully applied in many optimization
      problems. We define the new neighborhood conformation, tabu object and acceptance
      criteria of current conformation based on the original TS algorithm and put
      forward an improved TS algorithm. By integrating the heuristic initialization
      mechanism, the heuristic conformation updating mechanism, and the gradient method
      into the improved TS algorithm, a heuristic-based tabu search (HTS) algorithm is
      presented for predicting the two-dimensional (2D) protein folding structure in AB
      off-lattice model which consists of hydrophobic (A) and hydrophilic (B) monomers.
      The tabu search minimization leads to the basins of local minima, near which a
      local search mechanism is then proposed to further search for lower-energy
      conformations. To test the performance of the proposed algorithm, experiments are
      performed on four Fibonacci sequences and two real protein sequences. The
      experimental results show that the proposed algorithm has found the lowest-energy
      conformations so far for three shorter Fibonacci sequences and renewed the
      results for the longest one, as well as two real protein sequences, demonstrating
      that the HTS algorithm is quite promising in finding the ground states for AB off
      lattice model proteins. 

PMID- 24077544
TI  - [Epilepsy and the functional organization of the autonomic nervous system].
AB  - Results of the studies on the state of the autonomic nervous system (ANS) in
      symptomatic temporal epilepsy (TE) and frontal epilepsy (FE) are presented. It
      was investigated the functional state of catecholamine system, autonomic
      background, reaction and ANS supply in response to the physical and psycho
      emotional tests according to the clinical data, psychological testing and
      evaluation of the skin sympathetic response (SSR) as well as EEG parameters
      (paroxysmal index, slow activity in the background and in response to
      hyperventilation). The control group included healthy subjects. Comparison groups
      consisted of patients with panic attacks or with the combination of epilepsy and
      panic attacks. The disturbance of the self-regulation of catecholamine system and
      its exhaustion in TE were identified. The authors suggested the concept of the
      denervation hypersensitivity. According to the SSR, a start of the response to
      external stimuli always begins from the parasympathetic reaction both in healthy
      people and in all groups of patients studied. It means that the stable adaptive
      mechanism in the form of anticipating reaction from the side of the mechanisms
      stabilizing homeostasis had been formed during the phylogenies. Different
      patterns of the disturbance of ANS functional state in TE and FE were
      established. The data obtained indicate that the neocortical motor cortex has a
      direct relation to the suprasegmental formations which realize the ergotrophic
      supply of the motor activity. 

PMID- 24077545
TI  - [Hypochondriac symptoms in late-onset depression: the relationship between
      hypochondria and somatic state of patients].
AB  - Authors studied 276 women with late-onset depression. Concomitant chronic somatic
      diseases were identified in 90%. The presence of disease and its nosological
      definition did not impact on the development of hypochondriac symptoms in
      patients with late-onset depression. Patients with hypochondriac late-onset
      depression more often had disability pension due to somatic disease because they
      more often referred to internists in case of similar objective severity of
      somatic pathology. It was singled out three variants of the relationship between
      hypochondria and somatic state: hypernosognostic (a complete coincidence of
      hypochondria content with actual somatic pathology; anosognostic (a lack of
      coincidence) and disharmonic (a partial coincidence). The themes of hypochondria
      in late-nset depressions were correlated with a total number of somatic diseases
      and their severity. At the same time, there was no correlation between the
      content of hypochondria and the character of somatic disease. 

PMID- 24077546
TI  - [Early outcomes of Asperger's syndrome].
AB  - Mental state of adult patients, who since childhood had features of Asperger's
      syndrome (AS), was studied. We examined 107 patients (89 men and 18 women). At
      the moment of inclusion in the study, all the patients met criteria of ICD=10 for
      AS. This was confirmed by the examination of the patients with the help of ASDASQ
      and ASDI scales. Based on the results of psychopathological and psychological
      five variants of AS outcomes in the age of early adulthood were identified as
      follows: integrated, inhibitory, peculiar, border-line and hypernormative. At the
      moment of examination, psychosocial compensation was observed in 38% of patients,
      only 28% of patients were on treatment and 20% had a history of transitory
      psychotic episodes. The authors conclude that the results of the study suggest
      the relatively favorable prognosis of AS. The differential clinical evaluation of
      this group as well as implication of adequate psychosocial and psychotherapeutic
      methods in their treatment is needed. 

PMID- 24077547
TI  - [The effectiveness of dynamic proprioceptive correction in patients with cerebral
      palsy with cognitive impairment].
AB  - One hundred and sixty-seven patients with cerebral palsy (CP), aged 11-16 years,
      with spastic diplegia (n=87) and hemiparetic forms (n=80), with subgroups of
      mental retardation (MR) or intellectual delay (ID) have been studied. Standard
      treatment and application of a method of dynamic proprioceptive correction (MDPC)
      in the complex rehabilitation with the use of a medical and loading Adeli suit
      were used. Cognitive deficit in patients was characterized by the relative
      integrity of short-term nonverbal memory and marked impairment of verbal memory,
      verbal and nonverbal intellect. CP patients with intellectual delay demonstrated
      the predominant impairment of verbal functions. CP patients with mental
      retardation have the deficiency of both verbal and non-verbal cognitive
      functions. An individual profile of brain functional asymmetry in patients with
      CP was more lateralized than in healthy peers that can represent a mechanism for
      irregular development of cognitive functions in CP. Implementing the MDPC into
      comprehensive rehabilitation promotes the improvement of postural regulation and
      cognitive functions in children with CP compared to traditional methods of
      treatment. This is accompanied by the changes in functioning of the associative
      brain areas and hemispheric interaction. 

PMID- 24077548
TI  - [The use of biperiden (akineton) in patients with ephedrone encephalopathy].
AB  - An open comparative cross-over trial of the selective central M1 cholinoreceptors
      blocker - biperiden (akineton) was carried out in 35 patients with efedron
      encephalopathy (EEP) with mean illness duration 6,9 years. Patients received
      biperiden in individually adjusted dose, maximally up to 10 mg daily. Seventeen
      patients initially were treated with trihexyphenidyl in dosage 10 mg daily with
      switching to biperiden after 3 months. The total duration of treatment was 6
      months. There was a significant decrease on the Fahn-Marsden scale and a clinical
      EEP scale, along with the moderate improvement quality of life assessed with the
      EQ-5D and the increase of the Barthel index. The decrease on the Fahn-Marsden
      scale by more than 30% was found in 40% patients treated with biperiden during 6
      months and in 29% patients treated with trihexyphenidyl. Among patients switched
      to biperiden, 36% preferred to continue with the drug and only 12% preferred
      trihexyphenidyl. 

PMID- 24077549
TI  - [Attention deficit syndrome in adults: clinical, psychophysiological features and
      treatment].
AB  - The authors present the results of examination of 34 patients, aged from 18 to 30
      years, with attention deficit hyperactivity disorder (ADHD) (ICD-10 item F90.0).
      The study has shown that inattentive type of ADHD is noted in 50%, combined type
      in 38.3% and hyperactivity/impulsivity type in 11.7% of patients. Adult patients
      with ADHD also have a high level of anxiety and asthenic disorders. This study
      evaluated the efficacy and safety of adaptol in dosage 1500 mg daily during 8
      weeks in the treatment of this group of patients. The high efficacy (improvement
      in 64,7% of cases) and safety of adaptol confirmed by the data of clinical,
      psychological and neurophysiological studies. 

PMID- 24077550
TI  - [Event-related potentials in moderate cognitive impairment in patients with
      chronic cerebral ischemia treated with cytoflavin].
AB  - Authors compared cognitive functions in 60 patients (main group) with different
      stages of discirculatory encephalopathy (DE), I, II and III stages. A comparison
      group included 10 age-matched normals without DE. All patients underwent a
      clinical-neurological investigation and performed neuropsychological tests (MMSE,
      the Clock drawing test, Burdon probe) and Spilberger-Khanin test. Cognitive
      evoked potentials, including P300, were recorded. Results revealed the decrease
      in performance on neuropsychological tests and P300 components that indicated the
      slowing of metabolic processes in the cerebral cells of patients with DE. In
      patients treated with cytoflavin, the activation of metabolic processes in the
      brain cells that indicated the protection of the cellular cluster clinically
      manifested itself in neurocognitive and electrophysiological improvements was
      observed. 

PMID- 24077551
TI  - [Genomic abnormalities in children with mental retardation and autism: the use of
      comparative genomic hybridization in situ (HRCGH) and molecular karyotyping with
      DNA-microchips (array CGH)].
AB  - Genomic abnormalities occur with high frequency in children with mental
      retardation and autistic spectrum disorders (ADS). Molecular karyotyping using
      DNA microarrays is a new technology for diagnosis of genomic and chromosomal
      abnormalities in autism implemented in the fields of biological psychiatry and
      medical genetics. We carried out a comparative analysis of the frequency and
      spectrum of genome abnormalities in children with mental retardation and autism
      of unknown etiology using high-resolution comparative genomic methods for
      hybridization (HRCGH) and molecular karyotyping (array CGH). In a study of 100
      children with autism, learning difficulties and congenital malformations by
      HRCGH, we identified genomic rearrangements in 46% of cases. Using array CGH we
      examined 50 children with autism. In 44 cases out of 50 (88%), different genomic
      abnormalities and genomic variations (CNV - copy number variations) were
      identified. Unbalanced genomic rearrangements, including deletions and
      duplications, were found in 23 cases out of 44 (52%). These data suggest that
      genomic abnormalities which are not detectable by common methods of chromosome
      analysis are often discovered by molecular cytogenetic techniques in children
      autism spectrum disorders. In addition, 54 children with idiopathic mental
      retardation and congenital malformations (31 boys and 23 girls) without autism
      spectrum disorders were examined using molecular karyotyping and microarray
      containing an increased number of DNA samples for genomic loci of chromosome X.
      Deletions and duplications affecting different regions of the chromosome X were
      detected in 11 out of 54 children (20.4%). 

PMID- 24077552
TI  - [The association of COMT and DRD2 gene polymorphisms with a cognitive ability to
      understand others in schizophrenic patients].
AB  - To evaluate a role of dopamine transmission in the theory of mind (ToM)
      dysfunction in schizophrenia, authors studied the association of ToM with COMT
      and DRD2 gene polymorphisms in 209 patients with schizophrenia and 172 healthy
      people. All subjects performed second-order false belief (FB2) and faux pas
      stories. The association between the COMT Val158Met polymorphism and performance
      on FB2 was found. The association was sex-specific. The worse performance was
      associated with a Met allele in female patients and with the ValVal genotype in
      male ones. A correlation analysis of the COMT Val158Met polymorphism, performance
      on FB2 task, neurocognitive and clinical symptoms suggests that in female
      patients the association was modified, in part, by the higher stress sensitivity
      caused by the severity of clinical symptoms and its consequences for cognitive
      functioning. 

PMID- 24077553
TI  - [Shanges in heart rate variability in presymptomatic and symptomatic stages of
      Parkinson's disease under pharmacological influences: an experimental study].
AB  - The disbalance of autonomic heart regulation (AHR) develops already in the
      presymptomatic stage of Parkinson's disease. The early symptomatic stage is
      accompanied by the aggravation of heart dysfunction due to the shift of the
      autonomic balance towards the increase of sympathetic and decrease of
      parasympathic effect on the heart. Coronary disorders concomitant to Parkinson's
      disease increase a risk of life threatening arrhythmia and sudden death syndrome
      not only in the early symptomatic stage but also in the presymptomatic stage. L
      DOPA effectively restores the structure of AHR and prevents the risk of life
      threatening arrhythmia only in the presymptomatic stage of Parkinson's disease. 

PMID- 24077554
TI  - [Quality of life and social adaptation of patients with Guillain-Barre syndrome].

PMID- 24077555
TI  - [Kinesia paradoxica and cueing in parkinsonism: similarity and differences].

PMID- 24077556
TI  - Visuomotor process in movement correction: role of internal feedback loop.
AB  - This study examined the role of the internal feedback loop in movement correction
      during interceptive actions when what the performers expect to happen changes
      quickly. Eleven participants performed an interceptive task with a moving target
      under two conditions [Brief (8 m/s) or Long (4 m/s)]. We manipulated the
      probability of these target conditions to induce movement correction (20-80, 50
      50, and 80-20%) and delivered transcranial magnetic stimulation before movement
      initiation to disrupt the prediction of the movement consequence in the
      supplementary motor area of the cerebral cortex. In the 20% probability
      condition, which requires movement correction, the transcranial magnetic
      stimulation pulse had a significant adverse effect on the temporal error in the
      Brief condition, but not in the Long condition. The present results indicate that
      the internal feedback loop is crucial for movement correction for relatively
      brief interceptions. 

PMID- 24077557
TI  - Impaired prefrontal gamma band synchrony in autism spectrum disorders during gaze
      cueing.
AB  - Orienting to eye gaze is a vital social skill that is absent or developmentally
      delayed in autism spectrum disorders (ASD). Neural synchrony in the gamma
      frequency band is believed to be involved in perceptual and cognitive functions
      such as eye-gaze processing, and has been found to be abnormal in ASD. The
      current study used magnetoencephalography to measure neural synchrony in the
      gamma frequency band in neurotypicals (n=8) and individuals with ASD (n=10) while
      performing a directional eye-gaze processing task. Results support impaired
      generation of neural synchrony in the gamma frequency band during eye-gaze
      processing in ASD. Impaired gamma oscillatory activity in the prefrontal cortex
      may be associated with impairments in social cognitive functions such as eye-gaze
      processing in ASD. 

PMID- 24077558
TI  - The synthesis of chiral beta-aryl-alpha,beta-unsaturated amino alcohols via a Pd
      catalyzed asymmetric allylic amination.
AB  - Chiral beta-aryl-alpha,beta-unsaturated amino alcohols were synthesized via a Pd
      catalyzed asymmetric allylic amination of 4-aryl-1,3-dioxolan-2-one using planar
      chiral 1,2-disubstituted ferrocene-based phosphinooxazolines as ligands. Under
      the optimized reaction conditions, a series of substrates were examined and the
      products were obtained in good to excellent yields (up to 92%) and
      enantioselectivities (up to 98% ee) under mild reaction conditions. The desired
      products were determined to be of (R)-configuration and could subsequently be
      transformed into compounds with interesting biological activity using simple
      transformations. 

PMID- 24077559
TI  - Anti-leishmanial activity of heteroleptic organometallic Sb(v) compounds.
AB  - In seeking new drugs for the treatment of the parasitic disease Leishmaniasis, an
      extensive range of organometallic antimony(v) dicarboxylates of the form
      [SbR3(O2CR')2] have been synthesised, characterised and evaluated. The
      organometallic moieties (R) in the complexes vary in being Ph, tolyl (o, m or p),
      or benzyl. The carboxylates are predominantly substituted benzoates with some
      compounds incorporating acetato or cinnamato ligands. The crystal structures of
      [Sb(p-Tol)3(O2CC6H2-3,4,5-(OMe)3)2].0.5PhMe and [SbPh3(m-CH3C6H4CH2CO2)2] were
      determined and shown to adopt a typical trigonal pyramidal geometry, being
      monomeric with a five coordinate Sb centre. In total, the biological activity of
      26 Sb(v) compounds was assessed against the Leishmania major parasite, and also
      human fibroblast skin cells to give a measure of general toxicity. Of these, 11
      compounds (predominantly substituted benzoates with m- or p-tolyl ligands) proved
      to be highly effective against the parasite amastigotes at concentrations of 0.5
      3.5 MUM, while being non-toxic towards the mammalian cells at levels below 25
      MUM, making them highly promising drug candidates. 

PMID- 24077560
TI  - Preserved working memory and altered brain activation in persons at risk for
      psychosis.
AB  - OBJECTIVE: Patients with schizophrenia exhibit impairments in working memory that
      often appear in attenuated form in persons at high risk for the illness. The
      authors hypothesized that deviations in task-related brain activation and
      deactivation would occur in persons with an at-risk mental state performing a
      working memory task that entailed the maintenance and manipulation of letters.
      METHOD: Participants at ultra high risk for developing psychosis (N=60),
      identified using the Comprehensive Assessment of At-Risk Mental States, and
      healthy comparison subjects (N=38) 14 to 29 years of age underwent functional MRI
      while performing a verbal working memory task. Group differences in brain
      activation were identified using analysis of covariance. RESULTS: The two groups
      did not show significant differences in speed or accuracy of performance, even
      after accounting for differences in education. Irrespective of task condition, at
      risk participants exhibited significantly less activation than healthy comparison
      subjects in the left anterior insula. During letter manipulation, at-risk persons
      exhibited greater task-related deactivation within the default-mode network than
      comparison subjects. Region-of-interest analysis in the at-risk group revealed
      significantly greater right dorsolateral prefrontal cortex activation during
      manipulation of letters. CONCLUSIONS: Despite comparable behavioral performance,
      at-risk participants performing a verbal working memory task exhibited altered
      brain activation compared with healthy subjects. These findings demonstrate an
      altered pattern of brain activation in at-risk persons that contains elements of
      reduced function as well as compensation.

PMID- 24077561
TI  - A new type of microglia gene targeting shows TAK1 to be pivotal in CNS autoimmune
      inflammation.
AB  - Microglia are brain macrophages and, as such, key immune-competent cells that can
      respond to environmental changes. Understanding the mechanisms of microglia
      specific responses during pathologies is hence vital for reducing disease burden.
      The definition of microglial functions has so far been hampered by the lack of
      genetic in vivo approaches that allow discrimination of microglia from closely
      related peripheral macrophage populations in the body. Here we introduce a mouse
      experimental system that specifically targets microglia to examine the role of a
      mitogen-associated protein kinase kinase kinase (MAP3K), transforming growth
      factor (TGF)-beta-activated kinase 1 (TAK1), during autoimmune inflammation.
      Conditional depletion of TAK1 in microglia only, not in neuroectodermal cells,
      suppressed disease, significantly reduced CNS inflammation and diminished axonal
      and myelin damage by cell-autonomous inhibition of the NF-kappaB, JNK and ERK1/2
      pathways. Thus, we found TAK1 to be pivotal in CNS autoimmunity, and we present a
      tool for future investigations of microglial function in the CNS. 

PMID- 24077562
TI  - Computation of linear acceleration through an internal model in the macaque
      cerebellum.
AB  - A combination of theory and behavioral findings support a role for internal
      models in the resolution of sensory ambiguities and sensorimotor processing.
      Although the cerebellum has been proposed as a candidate for implementation of
      internal models, concrete evidence from neural responses is lacking. Using
      unnatural motion stimuli, which induce incorrect self-motion perception and eye
      movements, we explored the neural correlates of an internal model that has been
      proposed to compensate for Einstein's equivalence principle and generate neural
      estimates of linear acceleration and gravity. We found that caudal cerebellar
      vermis Purkinje cells and cerebellar nuclei neurons selective for actual linear
      acceleration also encoded erroneous linear acceleration, as would be expected
      from the internal model hypothesis, even when no actual linear acceleration
      occurred. These findings provide strong evidence that the cerebellum might be
      involved in the implementation of internal models that mimic physical principles
      to interpret sensory signals, as previously hypothesized. 

PMID- 24077563
TI  - Equalization of odor representations by a network of electrically coupled
      inhibitory interneurons.
AB  - Robustness of neuronal activity patterns against variations in input intensity is
      critical for neuronal computations. We found that odor representations in the
      olfactory bulb were stabilized by interneurons that were densely coupled to the
      output neurons by electrical and GABAergic synapses. This interneuron network
      modulated responses of output neurons as a function of stimulus intensity in two
      ways: it globally boosted responses to weak odors, but attenuated responses to
      strong odors, and it increased the sensitivity of some output neurons, but
      decreased the sensitivity of others. These effects are closely related to
      strategies used in engineering to increase dynamic range. Together, they
      maintained not only the mean, but also the distribution, of activity across the
      population of output neurons within narrow limits, which is important for pattern
      classification. Neuronal circuits in the olfactory bulb therefore stabilize
      combinatorial sensory representations against variations in stimulus intensity by
      generic mechanisms. 

PMID- 24077565
TI  - Category-specific integration of homeostatic signals in caudal but not rostral
      human insula.
AB  - Prevailing theories hold that the insula is functionally organized along its
      caudal-to-rostral axis, with posterior regions coding lower-level sensory
      information and anterior regions coding higher-level stimulus significance
      relative to the body's homeostatic needs. Contrary to predictions of this model,
      the response of the taste-sensitive region of the caudal, but not rostral, insula
      to food images was directly related to the body's homeostatic state as indexed by
      levels of peripheral glucose. 

PMID- 24077567
TI  - Model selection for prognostic time-to-event gene signature discovery with
      applications in early breast cancer data.
AB  - Model selection between competing models is a key consideration in the discovery
      of prognostic multigene signatures. The use of appropriate statistical
      performance measures as well as verification of biological significance of the
      signatures is imperative to maximise the chance of external validation of the
      generated signatures. Current approaches in time-to-event studies often use only
      a single measure of performance in model selection, such as logrank test p
      values, or dichotomise the follow-up times at some phase of the study to
      facilitate signature discovery. In this study we improve the prognostic signature
      discovery process through the application of the multivariate partial Cox model
      combined with the concordance index, hazard ratio of predictions, independence
      from available clinical covariates and biological enrichment as measures of
      signature performance. The proposed framework was applied to discover prognostic
      multigene signatures from early breast cancer data. The partial Cox model
      combined with the multiple performance measures were used in both guiding the
      selection of the optimal panel of prognostic genes and prediction of risk within
      cross validation without dichotomising the follow-up times at any stage. The
      signatures were successfully externally cross validated in independent breast
      cancer datasets, yielding a hazard ratio of 2.55 [1.44, 4.51] for the top ranking
      signature.

PMID- 24077566
TI  - Olfactory imprinting is triggered by MHC peptide ligands.
AB  - Olfactory imprinting on environmental, population- and kin-specific cues is a
      specific form of life-long memory promoting homing of salmon to their natal
      rivers and the return of coral reef fish to natal sites. Despite its ecological
      significance, natural chemicals for olfactory imprinting have not been identified
      yet. Here, we show that MHC peptides function as chemical signals for olfactory
      imprinting in zebrafish. We found that MHC peptides consisting of nine amino
      acids elicit olfactory imprinting and subsequent kin recognition depending on the
      MHC genotype of the fish. In vivo calcium imaging shows that some olfactory bulb
      neurons are highly sensitive to MHC peptides with a detection threshold at 1 pM
      or lower, indicating that MHC peptides are potent olfactory stimuli. Responses to
      MHC peptides overlapped spatially with responses to kin odour but not food odour,
      consistent with the hypothesis that MHC peptides are natural signals for
      olfactory imprinting. 

PMID- 24077564
TI  - Maturation of silent synapses in amygdala-accumbens projection contributes to
      incubation of cocaine craving.
AB  - In rat models of drug relapse and craving, cue-induced cocaine seeking
      progressively increases after withdrawal from the drug. This 'incubation of
      cocaine craving' is partially mediated by time-dependent adaptations at
      glutamatergic synapses in nucleus accumbens (NAc). However, the circuit-level
      adaptations mediating this plasticity remain elusive. We studied silent synapses,
      often regarded as immature synapses that express stable NMDA receptors with AMPA
      receptors being either absent or labile, in the projection from the basolateral
      amygdala to the NAc in incubation of cocaine craving. Silent synapses were
      detected in this projection during early withdrawal from cocaine. As the
      withdrawal period progressed, these silent synapses became unsilenced, a process
      that involved synaptic insertion of calcium-permeable AMPA receptors (CP-AMPARs).
      In vivo optogenetic stimulation-induced downregulation of CP-AMPARs at amygdala
      to-NAc synapses, which re-silenced some of the previously silent synapses after
      prolonged withdrawal, decreased incubation of cocaine craving. Our findings
      indicate that silent synapse-based reorganization of the amygdala-to-NAc
      projection is critical for persistent cocaine craving and relapse after
      withdrawal. 

PMID- 24077568
TI  - Cucurbita spp. and Cucumis sativus enhance the dissipation of polychlorinated
      biphenyl congeners by stimulating soil microbial community development.
AB  - A number of Cucurbita species have the potential to extract polychlorinated
      biphenyls (PCBs) from soil, but their impact on the soil microbial communities
      responsible for PCB degradation remains unclear. A greenhouse experiment was
      conducted to investigate the effect of three Cucurbita and one Cucumis species on
      PCB dissipation and soil microbial community structure. Compared to the unplanted
      control, enhanced losses of PCBs (19.5%-42.7%) were observed in all planted
      soils. Cucurbita pepo and Cucurbita moschata treatments were more efficient in
      PCB dissipation, and have similar patterns of soil phospholipid fatty acids
      (PLFAs) and PCB congener profiles. Cucurbita treatments tend to have higher soil
      microbial biomass than Cucumis. Gram-negative (G(-)) bacteria were significantly
      correlated with PCB degradation rates (R(2) = 0.719, p < 0.001), while fungi and
      G(-) bacteria were correlated with dissipation of the penta homologue group (R(2)
      = 0.590, p < 0.01). Therefore, Cucurbita related soil microorganisms could play
      an important role in remediation of PCB contaminated soils. 

PMID- 24077569
TI  - Incorporation of M(H2O)6(2+) between layers {M(H2O)2Ru2(CO3)4Cl2}n(2n-) (M = Zn,
      Mn): syntheses, structures and magnetic properties.
AB  - Isostructural heterometallic diruthenium carbonates
      KM(H2O)6[M(H2O)2Ru2(CO3)4Cl2].4H2O [M = Zn (1) and Mn (2)] were synthesized from
      the reaction of the precursors [Ru2(CO3)4Cl2](5-) and transitional metal ions in
      aqueous solution. Complexes 1 and 2 show layered structures in which Ru2(II,III)
      units are linked by four octahedral environment M(H2O)2(2+) ions in a cross
      fashion and vice versa giving a negative bimetallic square grid layer
      {M(H2O)2Ru2(CO3)4Cl2}n(3n-). M(H2O)6(2+) ions, linked by K(+) forming zigzag
      chain {KM(H2O)6}n(3+), are located in the void spaces between the layers. The
      adjacent bimetallic carbonate layers are connected with K-O and K-Cl bonds, and
      hydrogen bonding, forming a supramolecular 3D framework structure. Their magnetic
      properties were characterized in detail, and intralayer ferromagnetic coupling
      between the Ru2 dimer and Mn(2+) ion, as well as long-range ordering (Tc = 5.2 K)
      coexistence of domain movement behavior were observed for complex 2.

PMID- 24077570
TI  - Orthostatic hypotension in patients with dementia: clinical features and response
      to treatment.
AB  - OBJECTIVE: To evaluate orthostatic hypotension (OH) prevalence, risk factors,
      signs and symptoms, and treatment response in patients with dementia. BACKGROUND:
      No previous studies had systematically delineated the clinical features of OH in
      patients with dementia and determined the effects of treatment. Diagnosing this
      treatable disorder may prevent the severe consequences of falls, syncope,
      confusion, ischemic brain injury, and death; mortality risk rises with worsening
      OH. Lesser consequences include skin injuries, sprains, fractures, and subdural
      hematomas. METHODS: We reviewed the charts of 188 patients with dementia who had
      been treated by author D.F., a solo neurologist/neurobehaviorist. About half of
      the patients had been diagnosed with OH. D.F. had treated the OH until the
      patients had much improved blood pressure and symptoms, were asymptomatic, or no
      longer met OH diagnostic criteria. We collected data on diagnoses, blood
      pressures, and clinical features before and after treatment. RESULTS: Our
      patients' most frequent OH signs and symptoms were mental fluctuations (65.6% of
      patients), excessive sleeping in chairs (29.2%), slow falls without losing
      consciousness (20.8%), lethargy or fatigue (15.6%), and dizziness (13.5%). All 5
      of these signs and symptoms improved significantly with treatment. CONCLUSIONS:
      Patients with dementia were less likely to have traditional OH symptoms like
      dizziness than to have mental fluctuations and confusion, drowsiness, and slow
      falls. Blaming these problems on worsening dementia and neglecting OH as a
      potential cause may delay diagnosis and specific treatments that can improve
      patients' safety, daily function, and quality of life.

PMID- 24077571
TI  - Alexithymia and empathy predict changes in autonomic arousal during affective
      stimulation.
AB  - BACKGROUND: Alexithymia, the inability to describe one's own emotions, is linked
      to deficits in empathy, manifesting as a diminished capacity to recognize or
      understand the emotions and mental states of others. Several brain centers of
      autonomic control and interoception that are activated in empathy are thought to
      misfunction in alexithymia. We hypothesized that individual differences in
      autonomic changes under affective stimulation might be associated with
      differences in alexithymia and empathy. METHODS: We studied 21 healthy
      volunteers, comparing their alexithymia and empathy scores with changes in their
      sympathetic autonomic arousal, indexed by the palmar skin potential level, during
      3 tasks: playing a computer game, performing mental arithmetic, and watching a
      negative emotional valence video. RESULTS: Both autonomic and subjective sense of
      arousal increased at the beginning of each task and then gradually subsided over
      the course of the task. Higher autonomic arousal at the onset of the computer
      game was associated with higher empathy scores, and at the onset of the negative
      video with higher scores for both empathy and alexithymia. Alexithymia delayed
      the habituation of autonomic arousal during the computer game, while the empathy
      score was related to a faster decline in arousal during the negative video task.
      CONCLUSIONS: High alexithymia and high empathy scores were linked to increased
      autonomic arousal at the onset of emotional stimulation, but were distinguishable
      in the rates of habituation of the evoked arousal. Our data provide insight into
      the relationships among interacting psychological traits, physiologic regulation,
      and the arousal dimension of emotional experience.

PMID- 24077572
TI  - Hypometric allocentric and egocentric distance estimates in Parkinson disease.
AB  - OBJECTIVE AND BACKGROUND: Persons with Parkinson disease (PD) show hypometric
      movements and make hypometric estimates of imagined actions. These deficits may
      be related to misestimates of the length of body parts. Our objective was to
      learn whether patients with PD are impaired in their estimations of their arm's
      length and standard units of distance. METHODS: We tested 20 patients with PD,
      all on therapeutic doses of dopaminergic medications, and 13 healthy controls. In
      half of the trials, the participants stood so that either their right or left
      shoulder was adjacent to a wall; in the other half, their right or left shoulder
      was 5 feet from the wall. In the egocentric testing condition, they were asked to
      move their body toward or away from the wall to what they considered was an arm's
      length from the wall. In the allocentric testing condition, they were to move
      toward or away from the wall so that their proximal shoulder was a standard unit
      distance of 1, 2, or 3 feet from the wall. RESULTS: The patients with PD made
      much greater hypometric (too close to the wall) errors. Since at 5 feet from the
      wall they had to move farther to underestimate distances, their errors cannot be
      explained by hypometric movements. The results did not differ significantly by
      egocentric or allocentric estimation, side of shoulder proximity, or side of PD
      onset. CONCLUSIONS: Our findings support the idea that the egocentric and
      allocentric hypometria associated with PD is a perceptual rather than motor
      disorder.

PMID- 24077573
TI  - Usefulness of cube copying in evaluating clinical profiles of patients with
      Parkinson disease.
AB  - OBJECTIVE: To clarify the relationship between the quantitatively assessed cube
      copying test (CCT) and clinical profiles of cognitive and motor ability in
      Chinese patients with Parkinson disease (PD). METHODS: We gave the Montreal
      Cognitive Assessment (MoCA), which includes the CCT, to evaluate the cognitive
      function of 102 outpatients with PD. We also gave the Unified Parkinson's Disease
      Rating Scale (UPDRS) II and III and the Hoehn-Yahr scale to evaluate the
      patients' motor function and disease severity, respectively. We used Maeshima's
      method for quantitative assessment of the CCT, and calculated CCT errors by
      adding incomplete connections and plane-drawing errors. We divided the patients
      into 2 groups based on normal (no errors) versus abnormal (>=1 errors) CCT
      scores. RESULTS: We found 34 patients with normal scores and 68 with abnormal
      scores. The 2 groups had significant differences in age of onset, MoCA score,
      UPDRS II and III scores, and cognitive deterioration rate. CCT errors correlated
      inversely with cognitive domains except for orientation. Executive function was
      most commonly affected in both groups. We found correlations between numbers of
      CCT errors and left-limb movement, fine hand movement, postural instability and
      gait disorders, UPDRS II and III scores, and cognitive and motor deterioration
      rates. CONCLUSIONS: The quantitatively assessed CCT may be useful in estimating
      cognitive and motor dysfunction in patients with PD, and in monitoring disease
      progression.

PMID- 24077574
TI  - Psychosis and hallucinations in frontotemporal dementia with the C9ORF72
      mutation: a detailed clinical cohort.
AB  - OBJECTIVE: To specify the presenting symptoms and clinical course of patients
      with frontotemporal dementia (FTD) and chromosome 9 open reading frame 72
      (C9ORF72) repeat expansion. BACKGROUND: The 2011 discovery of the C9ORF72 repeat
      expansion causing familial FTD and amyotrophic lateral sclerosis has permitted
      retrospective evaluation of potential defining clinical characteristics that may
      distinguish carriers of the C9ORF72 mutation from other patients with FTD. Prior
      reports identified a subset of patients with FTD who had an unusually high
      prevalence of psychosis, although their specific symptoms had not yet been fully
      described. METHODS: From a cohort of 62 patients with FTD, we conducted a
      retrospective chart review of 7 patients who had C9ORF72 mutations on genetic
      testing, and 1 untested sibling of a C9ORF72 carrier. RESULTS: Detailed histories
      revealed a higher prevalence of psychosis, including visual and auditory
      hallucinations and delusions, in the 8 C9ORF72 carriers than in our patients with
      sporadic FTD. CONCLUSIONS: This cohort confirms and adds clinical details to the
      reports of a high prevalence of psychotic phenomena in patients who have C9ORF72
      mutations as well as FTD or amyotrophic lateral sclerosis.

PMID- 24077575
TI  - Vitamin D and long-term memory in multiple sclerosis.
AB  - BACKGROUND AND OBJECTIVE: Memory disturbance is a frequent cognitive complaint by
      patients with multiple sclerosis (MS). Recent dementia research suggests a
      beneficial role for vitamin D in long-term memory functioning. While data suggest
      ameliorative effects of vitamin D for the physical impairments of MS, it is
      unknown whether vitamin D can benefit the cognitive sequelae. We examined the
      relationship between serum levels of vitamin D and performance on verbal and
      nonverbal tests of long-term memory in patients with MS. METHODS: A sample of 35
      adults with relapsing-remitting MS completed cognitive testing and a vitamin D
      serum (25[OH]D) assay. Memory assessment used clinically established
      neuropsychological tests with multiple testing formats to determine whether
      vitamin D level was associated with memory during conditions of varying retrieval
      demands. Intellectual functioning and mood were also assessed to control for
      potential confounds. RESULTS: Vitamin D level was positively associated with
      performance on immediate and delayed recall trials of the Rey Complex Figure
      Test, effects that held after controlling for intelligence and disease duration.
      Vitamin D level was not associated with mood, intelligence, or verbal memory
      performance on the California Verbal Learning Test, Second Edition. CONCLUSIONS:
      Higher vitamin D level was associated with better nonverbal long-term memory
      performance in MS, particularly in conditions when no aid was given to help
      retrieval. These results supplement the literature on the neuroprotective effects
      of vitamin D and suggest that vitamin D is a worthwhile adjunct treatment for MS.

PMID- 24077576
TI  - Resolution of neuropsychological and FDG-PET abnormalities in a patient with
      neuropsychiatric systemic lupus erythematosus.
AB  - Many patients with systemic lupus erythematosus have central nervous system
      involvement. Routine diagnostic studies may not yield evidence of
      neuropsychiatric dysfunction and are therefore not useful as objective measures
      to monitor treatment response. We present a case of a 64-year-old woman whom we
      diagnosed with systemic lupus erythematosus by the American College of
      Rheumatology criteria after she reported recent cognitive decline.
      Neuropsychological assessment showed prominent deficits, and an F-18
      fluorodeoxyglucose positron emission tomography scan of the brain showed
      significant abnormalities. Both the neuropsychiatric and scan abnormalities
      improved dramatically with immunosuppressive treatment. F-18 fluorodeoxyglucose
      positron emission tomography shows promise in the diagnosis and treatment
      monitoring of patients who have lupus with neuropsychiatric involvement. 

PMID- 24077577
TI  - BLACK AND HISPANIC IMMIGRANTS' RESILIENCE AGAINST NEGATIVE ABILITY RACIAL
      STEREOTYPES AT SELECTIVE COLLEGES AND UNIVERSITIES IN THE UNITED STATES*
AB  - Stereotype threat is a widely supported theory for understanding the racial
      achievement gap in college grade performance. However, today's minority college
      students are increasingly of immigrant origins, and it is unclear whether two
      dispositional mechanisms that may increase susceptibility to stereotype threat
      are applicable to immigrants. We use survey data to examine whether and how
      negative ability stereotypes affect the grades of 1,865 first, second, and third
      generation or higher (domestic) minority students at 28 selective American
      colleges. Structural equation model results indicate that first generation
      immigrants are highly-resistant to both dispositional identity threat mechanisms
      we consider. Second generation immigrants experience only certain dispositional
      elements of identity threat. Drawing on research in social psychology, we suggest
      immigrants tend to resist stereotype threat in part due to the primacy of their
      immigrant identities and their connectedness to the opportunity structure of
      mainstream society.

PMID- 24077578
TI  - Preoperative particle and glue embolization of meningiomas: indications, results,
      and lessons learned from 117 consecutive patients.
AB  - BACKGROUND: Preoperative embolization of meningiomas remains contentious, with
      persisting uncertainty over the safety and efficacy of this adjunctive technique.
      OBJECTIVE: To evaluate the safety of presurgical embolization of meningiomas and
      its impact on subsequent transfusion requirement with respect to the extent of
      embolization and technique used. METHODS: One hundred seventeen consecutive
      patients between 2001 and 2010 were referred for embolization of presumed
      intracranial meningioma before surgical resection. Glue and/or particles were
      used to devascularize the tumor in 107 patients, all of whom went on to operative
      resection. The extent and nature of embolization-related complications, degree of
      angiographic devascularization, and the intraoperative blood transfusion
      requirements were analyzed. RESULTS: Mean blood transfusion requirement during
      surgery was 0.8 units per case (range, 1-14 units). Blood transfusion was
      significantly lower in patients whose meningiomas were completely,
      angiographically devascularized (P = .035). Four patients had complications as a
      direct result of the embolization procedure. These included intratumoral
      hemorrhage in 2, sixth cranial nerve palsy in 1, and scalp necrosis requiring
      reconstructive surgery in 1 patient. CONCLUSION: The complication rate was 3.7%.
      No relationship between the embolic agent and the degree of devascularization was
      observed. Achieving a complete devascularization resulted in a lower blood
      transfusion requirement, considered an indirect measure of operative blood loss.
      This series demonstrates that preoperative meningioma embolization is safe and
      may reduce operative blood loss. We present distal intratumoral injection of
      liquid embolic as a safe and effective alternative to more established particle
      embolization techniques.

PMID- 24077579
TI  - Endovascular balloon-assisted embolization of intracranial and cervical
      arteriovenous malformations using dual-lumen coaxial balloon microcatheters and
      Onyx: initial experience.
AB  - BACKGROUND: Ethylene vinyl alcohol copolymer (Onyx) is widely used for the
      embolization of arteriovenous malformations (AVMs) of the brain, head, and neck.
      Balloon-assisted Onyx embolization may provide additional unique advantages in
      the treatment of AVMs in comparison with traditional catheter-based techniques.
      OBJECTIVE: To report our initial experience in performing balloon-assisted AVM
      embolization for brain and neck AVMs with the use of the new Scepter-C and
      Scepter-XC coaxial dual-lumen balloon microcatheters. METHODS: Balloon-assisted
      transarterial embolization was performed in a series of 7 patients with AVMs (4
      with brain AVMs, 1 with a dural arteriovenous fistula, and 2 with neck AVMs) by
      using Onyx delivered through the lumen of Scepter-C or Scepter XC coaxial balloon
      microcatheters. Following the initial balloon-catheter navigation into a feeding
      artery and the subsequent inflation of the balloon, the embolization was
      performed by using Onyx 18, Onyx 34, or both. RESULTS: A total of 12 embolization
      sessions were performed via 17 arterial feeders in these 7 patients. In 1
      patient, there was an arterial perforation from the inflation of the balloon; in
      all others, the embolization goals were successfully achieved with no adverse
      events. CONCLUSION: The balloon microcatheters showed excellent navigability, and
      there were no problems with retrieval or with the repeated inflation and
      deflation of the balloons. A proximal Onyx plug, which is crucial in many AVM
      embolizations, was not necessary with this technique. Additionally, fluoroscopy
      and procedural times seemed lower with this technique compared with conventional
      embolization methods.

PMID- 24077580
TI  - Surgical treatment of spinal extradural arteriovenous fistula with parenchymal
      drainage: report on 5 cases.
AB  - BACKGROUND AND IMPORTANCE: Spinal extradural arteriovenous fistula (SEDAVF) with
      parenchymal drainage (type A) is a rare clinical entity that causes venous
      congestive myelopathy. Treatment includes endovascular and open microsurgical
      interventions. We reviewed the clinical records of patients treated for a type A
      SEDAVF to evaluate the feasibility of our treatment strategy. CLINICAL
      PRESENTATION: Between 2004 and 2010, 5 patients with a type A SEDAVF were treated
      at our institutes (4 men and 1 woman; mean age, 60 years). We performed
      endovascular transvenous embolization (TVE) when lesions were accessible
      transvenously; otherwise, microsurgical perimedullary drainer occlusion was
      performed. Follow-up ranged from 23 to 94 months (mean, 45.8 months). One patient
      was treated with TVE, and the remaining 4 were treated with microsurgical drainer
      occlusion. After a simple intradural drainer occlusion, an epidural venous lake
      was completely thrombosed in 2 patients. In 1 patient, postoperative angiography
      revealed that a part of the epidural component had persisted; however, the
      patient has been asymptomatic. In the remaining case with multiple intradural
      draining veins, sole drainer occlusion was not sufficient. A second surgery was
      required to meticulously coagulate the venous lake. As a consequence, parenchymal
      drainers disappeared. Overall, all patients stabilized or improved neurologically
      and experienced no recurrence. CONCLUSION: To treat a type A SEDAVF, either TVE
      or microsurgical intradural drainer occlusion can be used for satisfactory long
      term results with minimal surgical risks. For a case with multiple intradural
      draining veins, detachment of the venous lake should be considered.

PMID- 24077581
TI  - The volumetric response of brain metastases after stereotactic radiosurgery and
      its post-treatment implications.
AB  - BACKGROUND: Changes in tumor volume are seen on magnetic resonance imaging within
      weeks after stereotactic radiosurgery (SRS), but it remains unclear what clinical
      outcomes early radiological changes portend. OBJECTIVE: We hypothesized that
      rapid, early reduction in tumor volume post-SRS is associated with prolonged
      local control and favorable clinical outcome. METHODS: A retrospective review of
      patients treated with CyberKnife SRS for brain metastases at the University of
      North Carolina from 2007 to 2009 was performed. Patients with at least 1
      radiological follow-up, minimal initial tumor volume of 0.1 cm, no previous focal
      radiation, and no recent whole-brain radiation therapy were eligible for
      inclusion. RESULTS: Fifty-two patients with 100 metastatic brain lesions were
      analyzed and had a median follow-up of 15.6 months (range, 2-33 months) and a
      median of 2 (range, 1-8) metastatic lesions. In treated metastases in which there
      was a significant tumor volume reduction by 6 or 12 weeks post-SRS, there was no
      local progression for the duration of the study. Furthermore, patients with
      metastases that did not reduce in volume by 6 or 12 weeks post-SRS were more
      likely to require corticosteroids (P = .01) and to experience progression of
      neurological symptoms (P = .003). CONCLUSION: Significant volume reductions of
      brain metastases measured at either 6 or 12 weeks post-SRS were strongly
      associated with prolonged local control. Furthermore, early volume reduction was
      associated with less corticosteroid use and stable neurological symptoms.

PMID- 24077582
TI  - Embolization of spinal dural arteriovenous fistula via the retrocorporeal artery:
      case report.
AB  - BACKGROUND AND IMPORTANCE: The goal of spinal dural arteriovenous fistula (DAVF)
      treatment is to permanently occlude the proximal draining vein and the fistula
      itself, which can be achieved by open surgery or endovascular treatment. The
      endovascular approach is currently the primary treatment, but it requires the
      presence of an access as close to the site of the fistula as possible. This case
      illustrates that the retrocorporeal artery may be an alternative option in case
      of previous embolization failure with proximal occlusion of the radicular
      arteries. CLINICAL PRESENTATION: A 54-year-old man presented with an 18-month
      history of progressive paraparesis secondary to right L2 spinal DAVF. The first
      endovascular treatment failed to achieve occlusion of the fistula via the
      ipsilateral L2 and L3 radicular arteries. Given the proximal occlusion of these
      feeders during the first embolization, the dilated retrocorporeal arteries were
      approached via the contralateral L2 and L3 radicular arteries. Complete occlusion
      of the fistula was achieved with Onyx in a single session with progressive
      improvement of preoperative neurological deficit. CONCLUSION: The retrocorporeal
      artery may provide a safe alternative approach to spinal DAVFs in cases in which
      a conventional endovascular approach failed, thus avoiding invasive surgical
      treatment.

PMID- 24077584
TI  - The dilemma of early postoperative magnetic resonance imaging: when efficiency
      compromises accuracy: case report.
AB  - BACKGROUND AND IMPORTANCE: Postoperative magnetic resonance imaging (MRI) is
      critical to the clinical decision-making process for patients undergoing
      resection of intracranial tumors. The accuracy of immediate postoperative MRI in
      determining the presence of residual disease following intracranial tumor
      resection, however, has not been studied. CLINICAL PRESENTATION: A 57-year-old
      man underwent an uncomplicated retrosigmoid craniotomy for the resection of a
      cystic vestibular schwannoma. Immediate gadolinium-enhanced postoperative MRI,
      performed within 1.5 hours of surgery, was notable for a plaquelike, lobular,
      avidly enhancing collection with MRI characteristics consistent with fluid
      density extending from the porus acusticus into the cerebellopontine angle. This
      anomalous lesion disappeared upon repeat imaging 48 hours later, and the patient
      had no attributable clinical sequelae. He was discharged home without issues
      within 12 hours of repeat imaging. CONCLUSION: We demonstrate here that immediate
      postoperative, gadolinium-enhanced MRI scans after tumor resection may result in
      avid enhancement in the region of surgical manipulation, likely due to leakage of
      gadolinium chelates into the subarachnoid space from residual compromise of the
      blood-brain barrier immediately following surgical manipulation. Early imaging is
      no longer routinely performed at our institution unless otherwise clinically
      indicated. ABBREVIATIONS: FLAIR, fluid-attenuated inversion recoveryIAC, internal
      auditory canal.

PMID- 24077583
TI  - Comparison of Endovascular and Intraventricular Gene Therapy With Adeno
      Associated Virus-alpha-L-Iduronidase for Hurler Disease.
AB  - BACKGROUND: Hurler disease (mucopolysaccharidosis type I [MPS-I]) is an inherited
      metabolic disorder characterized by deficiency of the lysosomal enzyme alpha-L
      iduronidase (IDUA). Currently, the only therapies for MPS-I, enzyme replacement
      and hematopoietic stem cell transplantation, are generally ineffective for
      central nervous system manifestations. OBJECTIVE: To test whether brain-targeted
      gene therapy with recombinant adeno-associated virus (rAAV5)-IDUA vectors in an
      MPS-I transgenic mouse model would reverse the pathological hallmarks. METHODS:
      Gene therapy approaches were compared using intraventricular or endovascular
      delivery with a marker (rAAV5-green fluorescent protein) or therapeutic (rAAV5
      IDUA) vector. To improve the efficiency of brain delivery, we tested different
      applications of hyperosmolar mannitol to disrupt the blood-brain barrier or
      ependymal-brain interface. RESULTS: Intraventricular delivery of 1 * 10 viral
      particles of rAAV5-IDUA with systemic 5 g/kg mannitol co-administration resulted
      in IDUA expression throughout the brain, with global enzyme activity >200% of the
      baseline level in age-matched, wild-type mice. Endovascular delivery of 1 * 10
      viral particles of rAAV5-IDUA to the carotid artery with 29.1% mannitol blood
      brain barrier disruption resulted in mainly ipsilateral brain IDUA expression and
      ipsilateral brain enzyme activity 42% of that in wild-type mice. Quantitative
      assays for glycosaminoglycans showed a significant decrease in both hemispheres
      after intraventricular delivery and in the ipsilateral hemisphere after
      endovascular delivery compared with untreated MPS-I mice. Immunohistochemistry
      for ganglioside GM3, another disease marker, showed reversal of neuronal
      inclusions in areas with IDUA co-expression in both delivery methods. CONCLUSION:
      Physiologically relevant biochemical correction is possible with neurosurgical or
      endovascular gene therapy approaches for MPS-I. Intraventricular or endovascular
      delivery of rAAV5-IDUA was effective in reversing brain pathology, but in the
      latter method, effects were limited to the ipsilateral hemisphere.

PMID- 24077585
TI  - The artery of von Haller: a constant anterior radiculomedullary artery at the
      upper thoracic level.
AB  - BACKGROUND: Although recognized since the 18th century, radiculomedullary
      arteries (RMAs) originating from upper thoracic intersegmental arteries are
      generally considered to be inconstant branches of little clinical importance.
      Yet, such vessels are commonly observed during spinal angiography. OBJECTIVE: To
      evaluate the angiographic prevalence of upper thoracic RMAs, in particular,
      branches supplying the anterior spinal artery (ASA). METHODS: Fifty spinal
      angiograms were reviewed. Anterior and posterior RMAs originating in the upper
      thoracic region (T3 to T7) were recorded. The level of origin of the artery of
      Adamkiewicz (T8 to L3) was also noted. RESULTS: Forty-three patients (86%) had at
      least 1 ASA contributor between T3 and T7. Of the other 7 patients, 4 had one at
      an immediately adjacent level (T2 or T8). The most frequent origin of upper
      thoracic anterior RMAs was left T5 (n = 10). Only left T9 (n = 12) and left T8 (n
      = 11) were more common. When combining the left and right sides, an ASA
      contributor was more frequent at T5 (n = 16) than at any other level (n = 15 for
      T9, n = 14 for T8). The sum of ASA contributors at T4 and T5 (n = 27) represented
      54% of all upper thoracic anterior RMAs, and 23% of all anterior RMAs between T3
      and L3. CONCLUSION: A significant upper thoracic anterior RMA distinct from the
      artery of Adamkiewicz appears to be a constant anatomic feature, which undermines
      the classic concept of an arterial watershed zone in the thoracic region. We
      propose to name this artery after Albrecht von Haller, who documented its
      existence in 1754.

PMID- 24077586
TI  - Effectiveness of exercise-heat acclimation for preventing heat illness in the
      workplace.
AB  - The incidence of heat-related illness in the workplace is linked to whether or
      not workers have acclimated to a hot environment. Heat acclimation improves
      endurance work performance in the heat and thermal comfort at a given work rate.
      These improvements are achieved by increased sweating and skin blood flow
      responses, better fluid balance and cardiovascular stability. As a practical
      means of acclimatizing the body to heat stress, daily aerobic exercise training
      is recommended since thermoregulatory capacity and blood volume increase with
      physical fitness. In workers wearing personal protective suits in hot
      environments, however, little psychophysiological benefit is received from short
      term exercise training and/or heat acclimation because of the ineffectiveness of
      sweating for heat dissipation and the aggravation of thermal discomfort with the
      accumulation of sweat within the suit. For a manual laborer who works under
      uncompensable heat stress, better management of the work rate, the work
      environment and health is required. 

PMID- 24077587
TI  - Case of multiple endocrine neoplasia 2B with probable ectopic adrenocorticotropic
      hormone-secreting liver metastasis from medullary thyroid carcinoma.
AB  - A 31 year old woman was diagnosed with multiple endocrine neoplasia (MEN) 2B at
      10 years old. Dark pigmentation gradually developed on her skin and her serum
      adrenocorticotropic hormone (ACTH) was high, suggesting concurrent ectopic ACTH
      syndrome (EAS). Corticotropin-releasing hormone (CRH) loading test ruled out
      Cushing's disease and supported the diagnosis of EAS. Multiple low attenuation
      mass in the liver was observed in a computed tomography (CT) scan, and was
      suspected as ectopic ACTH-secreting metastatic tumor from medullary thyroid
      carcinoma (MTC). ACTH production by MTC is relatively rare, particularly in
      patients with MEN; patients with ectopic ACTH-secreting liver metastatic tumor
      from MTC in MEN 2B have never been reported previously. 

PMID- 24077588
TI  - [Verification of the hygienic hypothesis by evaluating the regional incidence of
      eosinophilic pustular folliculitis].
AB  - Eosinophilic pustular folliculitis (EPF) is a disorder associated with a high
      expression of interleukin-5 by T helper 2 cells. Treatment involving T helper 1
      (Th1) modulation has been shown to be effective. We report that the occurrence of
      Bowen's disease in the medical care zone of the University of Occupational and
      Environmental Health in the Kitakyushu industrial area is more frequent in
      Yahatahigashi-ku, Yahatanishi-ku, and Wakamatsu-ku than in Tobata-ku, Kokurakita
      ku, and Kokuraminamiku. We also show that these cases are more common in the
      regions with steel- and coal-related industries, which is suggestive of a higher
      rate of Th1 modulation associated with these occupations. Similarly, the
      incidence of EPF per unit population was found to be high in Tobata-ku and low in
      Yahatahigashi-ku, which indicates that EPF is a typical disease of hygiene
      hypothesis.

PMID- 24077589
TI  - [Effect of metformin in elderly type 2 diabetes].
AB  - It has become possible in Japan to use high-dose metformin for patients with type
      2 diabetes. The aim of this retrospective study was to determine the effects and
      safety of metformin in elderly patients with type 2 diabetes. The study subjects
      (98 patients who were treated with metformin) were assigned into two groups: (I)
      59 patients who were younger, aged less than 65 years, and (II) 39 patients who
      were elderly, aged more than 65 years. The primary endpoint was the change in
      glycosylated hemoglobin A1c (HbA1c) at 12 weeks. The secondary endpoints were the
      safety variables, including hypoglycemic events and adverse events. Although
      HbA1c decreased significantly in both group I (-0.5%) and group II (-0.9%), the
      difference between the two groups in the change in HbA1c was not significant.
      There were no incidences of hypoglycemia or adverse events in either group.
      Metformin improved glycemic control in the elderly patients as well as in the non
      elderly patients. It is necessary to examine what dose of metformin and serum
      creatinin level (Cre), eGFR is appropriate for elderly patients.

PMID- 24077590
TI  - [Case of primary lymphoplasmacytic lymphoma limited to the paratracheal
      mediastinum].
AB  - A 54 year old Japanese man was introduced to Saiseikai General hospital for an
      evaluation of an abnormal chest X-ray film. Abnormal soft tissue area was
      observed in the mediastinum surrounding anterior area of the trachea on chest CT.
      Because the mediastinal tumor showed slow enlargement after temporal decrease and
      surgical resection of the tumor was performed 3 years after the first visit.
      Pathologically, diffuse proliferation of oval-shaped plasmacytic or small
      lymphocytic cells with eccentrically-located nuclei with rough chromatin were
      observed in the tumor. Immunohistochemically, these cells were positive for CD20,
      weakly positive for IgM, negative for CD3, CD5, CD10, suggesting
      lymphoplasmacytic lymphoma (LPL). The patient was treated with rituximab after
      the surgical treatment, and showed no exacerbation for 3.5 years after surgery.
      LPL localized to the paratracheal mediastinum is rare, and a surgical approach is
      important for prompt and proper diagnosis. 

PMID- 24077591
TI  - [Implementation of acute stroke rehabilitation services in our hospital 
      comparison between the years 2010 and 2000-].
AB  - We retrospectively compared the stroke rehabilitation services in our hospital in
      2010 with those in 2000. The severity of strokes in 2010 was worse than that in
      2000. The period between the onset of stroke and beginning of physical therapy
      was shortened from 11.3 days to 4.0 days, and the period between prescription and
      beginning of physical therapy was shortened from 1.1 days to 0.2 days. We
      consider that two reasons for these changes were that requests to the department
      of rehabilitation came at earlier stages in the development of symptoms and that
      we could shift chronic rehabilitation services to acute rehabilitation services
      due to an increase in the number of physical therapists. Introducing the
      electronic medical record system might also have been efficient for these
      changes. 

PMID- 24077592
TI  - [Evaluation of the application of the clinical pathway using Diagnosis Procedure
      Combination (DPC) data].
AB  - The clinical pathway (CP) is a schedule of a standard set of treatments for a
      particular clinical condition. The horizontal axis of the CP indicates
      hospitalization days and the vertical axis indicates a set of procedures for each
      day. Using the CP, medical staff (i.e., physicians and nurses) and patients can
      have a clear image of the content of treatment and its schedule, and can
      understand the tests, operation schedules and the aim of the discharge day, and
      avoid excessive or deficient tests and care. The health care service can function
      smoothly as a team because it is clear who is responsible for what. However, it
      requires a considerable amount of time and work for medical staff to evaluate
      clinical activities based on the established CP, to monitor the appropriateness
      of the CP, and to modify its content if necessary. Because of this, it is not
      rare for hospital staff to stop using CPs. In this study, we tried to develop a
      method to systematically evaluate the appropriate level of CP based on Diagnosis
      Procedure Combination (DPC) data. Furthermore, we developed a methodology to
      formulate a new CP based on DPC data. The present study has clarified that
      management staff can support medical staff in CP - based clinical evaluation and
      CP development by using the DPC data. This kind of partnership between management
      and medical staffs should contribute to the standardization and amelioration of
      clinical quality. 

PMID- 24077593
TI  - [Psychological processes and readaptation to life in society of elderly
      widowers].
AB  - This study used a literature review to examine the psychological processes and
      readaptation to life in society of elderly widowers. The psychological
      restoration process after a bereavement is different among individuals, and there
      are various types of coping patterns. However the relationship between the
      psychological process after a bereavement and the psychological isolation caused
      by environmental factors of having social roles in the community or not, have not
      yet been clarified. Further research is needed on these points to support elderly
      widowers in their readaptation to life in society. 

PMID- 24077595
TI  - Legend omitted and number misrepresented.

PMID- 24077596
TI  - Motor unit changes seen with skeletal muscle sarcopenia in oldest old rats.
AB  - Sarcopenia leads to many changes in skeletal muscle that contribute to atrophy,
      force deficits, and subsequent frailty. The purpose of this study was to
      characterize motor unit remodeling related to sarcopenia seen in extreme old age.
      Whole extensor digitorum longus muscle and motor unit contractile properties were
      measured in 19 adult (11-13 months) and 12 oldest old (36-37 months) Brown-Norway
      rats. Compared with adults, oldest old rats had significantly fewer motor units
      per muscle, smaller muscle cross-sectional area, and lower muscle specific force.
      However, mean motor unit force generation was similar between the two groups due
      to an increase in innervation ratio by the oldest old rats. These findings
      suggest that even in extreme old age both fast- and slow-twitch motor units
      maintain the ability to undergo motor unit remodeling that offsets some effects
      of sarcopenia. 

PMID- 24077598
TI  - Loneliness, health, and longevity.
AB  - BACKGROUND: Objective measures of loneliness and poor social contacts are
      associated with negative health outcomes. However, the influence of subjective
      loneliness among elderly persons is poorly documented. We hypothesized that
      loneliness among persons aged 70-90 years is associated with subsequent decline
      in health, function, and longevity. METHODS: Mortality data for subjects aged 70
      90 years were obtained; subjective loneliness, health, comorbidity, depression,
      and functional status were assessed through the Jerusalem Longitudinal Cohort
      Study (1990-2010), a prospective longitudinal study. A representative sample of
      407, 661, and 1,113 participants born 1920-1921 were assessed at home at ages 70,
      78, and 85, respectively. Participants were asked how often they felt lonely,
      with answers dichotomized to never versus rarely/often/very often. In the age
      group of 70, 78, and 85, we excluded 67, 141, and 408 depressed participants from
      the study sample, which, thus, comprised 340, 520, and 705 participants,
      respectively. RESULTS: At age 70, 78, and 85, prevalence of loneliness was 27.9%
      (n = 95), 23.8% (n = 124), and 24% (n = 169), respectively. The only factor
      consistently associated at all ages with increased likelihood of loneliness was
      not being married. After adjusting for baseline variables, we found no
      association between loneliness and subsequent deterioration 7 years later in
      functional status, mood, cognition, chronic pain, or rising comorbidity between
      ages 70 and 78 or 78 and 85. Loneliness was not associated with mortality among
      the participants aged 70-78, 78-85, and 85-90. We repeated all data analysis,
      without excluding depressed participants, without any change in overall findings.
      CONCLUSIONS: Our findings do not support the hypothesis that subjective
      loneliness is associated with increased morbidity or mortality from age 70 to 90.

PMID- 24077597
TI  - Longitudinal analysis of calorie restriction on rat taste bud morphology and
      expression of sweet taste modulators.
AB  - Calorie restriction (CR) is a lifestyle intervention employed to reduce body
      weight and improve metabolic functions primarily via reduction of ingested
      carbohydrates and fats. Taste perception is highly related to functional
      metabolic status and body adiposity. We have previously shown that sweet taste
      perception diminishes with age; however, relatively little is known about the
      effects of various lengths of CR upon taste cell morphology and function. We
      investigated the effects of CR on taste bud morphology and expression of sweet
      taste-related modulators in 5-, 17-, and 30-month-old rats. In ad libitum (AL)
      and CR rats, we consistently found the following parameters altered significantly
      with advancing age: reduction of taste bud size and taste cell numbers per taste
      bud and reduced expression of sonic hedgehog, type 1 taste receptor 3 (T1r3),
      alpha-gustducin, and glucagon-like peptide-1 (GLP-1). In the oldest rats, CR
      affected a significant reduction of tongue T1r3, GLP-1, and alpha-gustducin
      expression compared with age-matched AL rats. Leptin receptor immunopositive
      cells were elevated in 17- and 30-month-old CR rats compared with age-matched AL
      rats. These alterations of sweet taste-related modulators, specifically during
      advanced aging, suggest that sweet taste perception may be altered in response to
      different lengths of CR. 

PMID- 24077599
TI  - Neuropathologic changes associated with atrial fibrillation in a population-based
      autopsy cohort.
AB  - BACKGROUND: Atrial fibrillation (AF) is associated with higher risk of dementia
      and Alzheimer's disease. To better understand the mechanism, we examined
      neuropathologic changes seen with AF. METHODS: We analyzed data from an autopsy
      series arising from a population-based, prospective cohort study set within Group
      Health, an integrated health care delivery system. Participants were people aged
      65 and older, community-dwelling, and nondemented at study enrollment, who died
      during follow-up and underwent autopsy. AF was defined from medical records.
      Permanent AF was defined as having two or more electrocardiograms showing AF
      between 6 and 36 months apart with no evidence of sinus rhythm in between. The
      primary study outcomes were gross infarcts, neuritic plaques, and neurofibrillary
      tangles, ascertained using consensus guidelines. Adjusted relative risks and 95%
      CIs were calculated using modified Poisson regression, weighted to account for
      selection into the autopsy cohort. RESULTS: Three hundred and twenty-eight
      participants underwent autopsy; 134 (41%) had AF. People with AF were more likely
      to have gross infarcts than those without AF (45% vs 31%; relative risk 1.82, 95%
      CI 1.23-2.71); in 30%, these infarcts were not clinically recognized before
      death. Alzheimer's disease neuropathologic changes were not associated with ever
      having AF but were more common in people with permanent AF. Adjusted relative
      risks for frequent neuritic plaques and neurofibrillary tangles were 1.47 (0.96
      2.28) and 1.40 (0.79-2.49), respectively, for people with permanent AF versus no
      AF. CONCLUSIONS: AF is associated with gross infarcts. Permanent AF may
      contribute to Alzheimer's disease neuropathologic changes, but more study is
      needed.

PMID- 24077600
TI  - Virtual drug design: Skp1-Skp2 inhibition targets cancer stem cells.
AB  - The dysregulation of pathways regulating cellular function is a frequent hallmark
      of cancer and the development of specific pathway inhibitors that alter tumor
      growth and progression are the focus of multiple recent studies. E3 ubiquitin
      ligases are a large group of diverse protein enzymes that specifically target
      proteins for clearance, and their importance to normal cellular function is
      illustrated in the many diseases associated with their loss of function or
      inappropriate targeting. S-phase kinase-associated protein 2 (Skp2) is an F box
      protein that plays critical roles in cell-cycle progression, senescence,
      metabolism, and acts as an Skp1-Cullin-1-F box (SCF) ubiquitin ligase substrate
      recognition factor. Overexpression of Skp2 is associated with poor prognosis and
      metastasis in many cancers and is a well validated drug target. In a recent
      report, Chan et al. have identified an Skp2 inhibitor that selectively impairs
      Skp2 E3 ligase activity using an integrated virtual high-throughput drug
      screening and experimental validation approach. This Skp2 inhibitor restricts
      cancer stemness and potentiates sensitivity to chemotherapeutic agents in
      multiple animal tumor models. These findings identify a new novel small molecule
      that targets the Skp2 and reduces tumor growth by attenuating aerobic glycolysis
      and inducing cellular senescence.

PMID- 24077601
TI  - Autonomic nerve development contributes to prostate cancer progression.
AB  - In a significant translational study, Magnon et al. investigated the role that
      the autonomic nervous system plays in the development and spread of prostate
      cancer in both mice and human models. The study shows different roles for both
      branches of the autonomic nervous system, with the sympathetic system promoting
      early stages of tumorigenesis, and the parasympathetic system promoting cancer
      dissemination. This information could lead to important new foundations for
      treatment, therapies and management of prostate cancer.

PMID- 24077602
TI  - Scaffold attachment factor B1: an intrinsic inhibitor of androgen receptor
      downregulated in prostate cancer.
AB  - The androgen receptor (AR) is a pleiotrophic transcription factor that regulates
      expression of a large number of genes involved in many diverse cellular
      processes. The AR activation pathways have been studied extensively. However, the
      molecular mechanism and biological significance of AR inhibitory signals remain
      poorly understood. Mukhopadhyay et al. have now identified the nuclear matrix
      protein scaffold attachment factor B1 (SAFB1) as a novel AR corepressor. The
      authors found that SAFB1 physically associates with AR protein and inhibits AR
      transcriptional activity and androgen-sensitive gene expression. SAFB1 had no
      effect on chromatin occupancy of AR, but silencing of SAFB1 abolished recruitment
      MST1, a known AR repressor, at AR target loci. They also showed that SAFB1
      interacts with EZH2, SUZ12 and EED, three core components of the Polycomb
      repressive complex 2 (PRC2), which catalyzes the gene repression histone
      modification H3 lysine 27 trimethylation (H3K27me3). The authors further showed
      that forced expression of SAFB1 increases H3K27me3 at AR target loci and this
      effect requires EZH2. Finally, the authors demonstrated that expression of SAFB1
      is downregulated in human prostate cancer (PCa) specimens and SAFB1 knockdown
      results in an aggressive phenotype of PCa. These findings identify SAFB1 as an
      important node for integration of multiple inhibitory signals of AR, which
      represents a viable pathway for therapeutic intervention of PCa.

PMID- 24077603
TI  - CYCLES OF POVERTY, FOOD INSECURITY, AND PSYCHOSOCIAL STRESS AMONG AIDS CARE
      VOLUNTEERS IN URBAN ETHIOPIA.
AB  - With the rollout of AIDS therapies, volunteer AIDS care has been promoted across
      Africa under the assumption that volunteerism is economically imperative in
      settings of health professional and resource scarcity. As low-income volunteers
      have become a major part of HIV/AIDS prevention and treatment workforces, it is
      imperative to question how poverty impacts their well-being. This chapter
      presents epidemiologic data collected during the 2008 food crisis from a sample
      of 110 AIDS care volunteers in Addis Ababa, Ethiopia, as well as narratives
      offered by HIV-positive volunteers, highlighting a widely overlooked way in which
      food insecurity and mental distress impact efforts to treat AIDS in sub-Saharan
      Africa. Food insecurity and elevated common mental disorder (CMD) symptom loads
      were common and tightly linked among the volunteers in the sample. Volunteers who
      were HIV-positive (17 percent) fared slightly worse in terms of food insecurity
      and psychosocial well-being. However, positive HIV serostatus was not associated
      with CMD in multivariate analyses accounting for food insecurity. Narratives
      illustrate how being HIV-positive shaped experiences of psychosocial stress,
      which involved unemployment and lack of prospects for marital relationships or
      strife within them. Our focus demonstrates the potential for mixing ethnographic
      and epidemiological methods to inform policy questions regarding poverty
      reduction through compensation for volunteers' valuable labor, as well as AIDS
      care program sustainability. [volunteerism, AIDS care, food insecurity,
      livelihoods, HIV, psychosocial health].

PMID- 24077604
TI  - Arterial grafting and complete revascularization: challenge or compromise?
AB  - PURPOSE OF REVIEW: Arterial grafting is superior to venous grafting in coronary
      artery bypass graft surgery with respect to graft patency and long-term patient
      outcome, but it may be difficult to achieve complete arterial revascularization.
      RECENT FINDINGS: Use of arterial grafts, especially bilateral internal mammary
      artery grafts, is not common, whereas there are clear indications that it may
      increase survival. Definitions of complete revascularization are varied and
      confusing, making study comparisons difficult. Technical challenges in complete
      revascularization with arterial grafts can be minimized by surgical techniques.
      Competitive flow in moderately stenosed coronary arteries grafted with arterial
      conduits may result in reduced patency. While internal mammary arteries may be
      used in arteries with at least 60% stenosis, radial artery and gastroepiploic
      grafts are best placed onto coronaries with severe stenosis. Moderate lesions in
      the left coronary circulation should be bypassed, but right coronary artery
      lesions can be left untouched as there is minimal progression over time. Complete
      revascularization may not be necessary or possible in every patient because of
      technical challenges. CONCLUSION: Complete revascularization with arterial grafts
      presents both technical and physiological challenges. However, with techniques to
      maximize length of arterial conduits, knowledge of competitive flow and which
      moderate lesions should be addressed, complete revascularization with arterial
      grafts can be accomplished in the majority of patients, notwithstanding it may
      not be possible or even indicated for every patient.

PMID- 24077605
TI  - Therapeutic strategies to prevent contrast-induced acute kidney injury.
AB  - PURPOSE OF REVIEW: Contrast-induced acute kidney injury (CI-AKI) accounts for
      approximately 10% of all causes of hospital-acquired renal failure, causes a
      prolonged in-hospital stay, and represents a powerful predictor of poor early and
      late outcome. Here, we highlight endpoints used to assess major strategies to
      prevent CI-AKI. RECENT FINDINGS: A general consensus exists on the beneficial
      prophylactic effect of hydration. This seems to act by increasing urine flow rate
      and, thereby, by limiting the time of contact between the contrast media and the
      epithelial tubular cells. On the contrary, both observational trials and
      randomized studies are often controversial in their conclusions on the efficacy
      of several drugs tested to prevent CI-AKI. Compounds evaluated include diuretics
      (furosemide), antioxidants (i.e., N-acetylcysteine and statins), and vasodilators
      (i.e., calcium antagonists, dopamine, and fenoldopam). Due to the negative and/or
      controversial clinical results, none of these drugs has been currently
      recommended to prevent CI-AKI. CONCLUSION: More reliable markers of acute kidney
      injury and new prophylactic strategies are warranted to prevent the incidence of
      CI-AKI.

PMID- 24077607
TI  - Intraaortic balloon pump use in high-risk percutaneous coronary intervention.
AB  - PURPOSE OF REVIEW: Despite the long-term availability and clinical usage of
      intraaortic balloon pump (IABP) counterpulsation, there is a paucity of
      randomized trial evidence for its use. Here, we will review the latest evidence
      for its usage in different clinical settings. RECENT FINDINGS: There have been
      decades of nonrandomized and observational data available, but only in the last 3
      years has there been availability of randomized evidence for IABP use in acute
      myocardial infarction (AMI) with cardiogenic shock, ST elevation acute coronary
      syndromes (STE-ACS) without shock and high-risk percutaneous coronary
      intervention (PCI) cohorts. SUMMARY: To the surprise of many, despite the sound
      physiological benefits achieved by the use of IABP counterpulsation in these
      situations, all the recent trials did not achieve the primary endpoint, although
      there is a trend towards long-term benefit with its use. This may alter its
      elective use in practice and may lead to changes in current guidance and possibly
      increase the focus on other mechanical circulatory devices. Despite the neutral
      primary endpoints in these recent trials, there is a signal that a subset of the
      population may benefit by elective IABP use and get good haemodynamic support,
      thus suggesting, in our view, that further understanding and research are
      required to gain maximum physiological benefit from this device and to aid
      decision making for an individualized, patient-centred approach.

PMID- 24077606
TI  - Time-perspective in cardiovascular risk of NSAID use after first-time myocardial
      infarction.
AB  - PURPOSE OF REVIEW: Despite the fact that NSAIDs are not recommended among
      patients with established cardiovascular disease, many patients receive NSAID
      treatment for a short period of time. However, up until recently, data on the
      relationship between treatment duration and associated cardiovascular risk were
      sparse and have not been summarized. RECENT FINDINGS: A series of recent studies
      of patients with prior myocardial infarction (MI) demonstrated that short-term
      treatment with most NSAIDs is associated with an increased cardiovascular risk
      relative to no NSAID treatment. These studies furthermore demonstrated that NSAID
      use among patients with first-time MI was associated with persistently increased
      risk of all-cause mortality and of a composite of coronary death or nonfatal
      recurrent MI for at least 5 years thereafter. SUMMARY: The present review
      indicates that there is no apparent well-tolerated therapeutic window for
      associated cardiovascular risk and NSAID use in patients with prior MI. Further
      randomized studies are warranted to evaluate the cardiovascular safety of NSAIDs,
      but, at this point, the overall evidence suggests advising caution in using
      NSAIDs at all times after MI. Legislation bodies need to address this issue of
      public health proportions, as studies have shown that utilization rates of NSAID
      keep increasing.

PMID- 24077608
TI  - Minimally invasive coronary artery bypass grafting: is it time for the robot?
AB  - PURPOSE OF REVIEW: Minimally invasive coronary artery bypass grafting (MICS CABG)
      consists of single-vessel or multivessel revascularization via a small left
      thoracotomy, and has been proposed as an alternative to a standard sternotomy
      approach. The purpose of this article is to examine the current status of MICS
      CABG and discuss its future directions. RECENT FINDINGS: Experience in the first
      450 cases was reported in 2009, and established the efficacy and safety of a
      small thoracotomy approach for multivessel and single-vessel revascularization.
      In addition to earlier recovery and rehabilitation, MICS CABG is associated with
      fewer transfusions and fewer wound infections than off-pump CABG. Recently, the
      MICS CABG Patency Study showed excellent graft patency in patients assessed by 64
      slice computed tomography angiography 6 months after operation. We also showed
      that the use of cardiopulmonary bypass assistance may help alleviate some of the
      learning curve inherent in this operation. SUMMARY: MICS CABG has developed into
      a reproducible, high-quality, complete surgical revascularization alternative to
      conventional CABG. Preservation of sternal integrity allows patients to recover
      earlier, require fewer transfusions, and experience fewer infections. Further
      research on expanding the applicability of MICS CABG and enhancing its advantages
      over conventional CABG is warranted.

PMID- 24077609
TI  - Percutaneous coronary intervention for postcardiac arrest syndrome.
AB  - PURPOSE OF REVIEW: Sudden cardiac arrest is a major cause of unexpected death, as
      well as a major clinical issue. Primary percutaneous coronary intervention (PCI)
      can drastically improve outcomes among patients with ST-elevation myocardial
      infarction without cardiac arrest. Recent studies reported that using emergency
      PCI to resuscitate patients has the potential to improve their outcomes. The
      purpose of this review is to elucidate the effects of PCI among resuscitated
      patients. RECENT FINDINGS: To the best of current understanding, no randomized
      clinical trial has assessed PCI for postcardiac arrest syndrome. Several
      observational studies suggested a positive effect of PCI for resuscitated out-of
      hospital cardiac arrest (OHCA) patients, and a number of observational studies
      reported a limited beneficial effect. Several studies reported that a combination
      of therapeutic hypothermia and PCI may be feasible and effective. However, the
      presence of bias and unmeasured confounders in these studies may have affected
      the outcomes. SUMMARY: PCI for postcardiac arrest syndrome may improve outcomes
      of OHCA patients; however, randomized trials of PCI for postcardiac arrest
      syndrome are necessary to confirm this issue. Alternative cardiopulmonary
      resuscitation using venoarterial extracorporeal membrane oxygenation and PCI may
      have the potential to improve the outcomes of refractory cardiac arrest patients.

PMID- 24077610
TI  - Reconstruction of Sensory Stimuli Encoded with Integrate-and-Fire Neurons with
      Random Thresholds.
AB  - We present a general approach to the reconstruction of sensory stimuli encoded
      with leaky integrate-and-fire neurons with random thresholds. The stimuli are
      modeled as elements of a Reproducing Kernel Hilbert Space. The reconstruction is
      based on finding a stimulus that minimizes a regularized quadratic optimality
      criterion. We discuss in detail the reconstruction of sensory stimuli modeled as
      absolutely continuous functions as well as stimuli with absolutely continuous
      first-order derivatives. Reconstruction results are presented for stimuli encoded
      with single as well as a population of neurons. Examples are given that
      demonstrate the performance of the reconstruction algorithms as a function of
      threshold variability.

PMID- 24077611
TI  - Atomic structure of titania nanosheet with vacancies.
AB  - Titania nanosheets are two-dimensional single crystallites of titanium oxide with
      a thickness of one titanium or two oxygen atoms, and they show attractive
      material properties, such as photocatalytic reactions. Since a titania (Ti0.87O2)
      nanosheet is synthesized by the delamination of a parent layered
      K0.8Ti1.73Li0.27O4 crystal using a soft chemical procedure, substantial Ti
      vacancies are expected to be included and affect the material properties. The
      atomic arrangement of a titania nanosheet with vacancies has not been revealed
      owing to the difficulties of direct observation. Here, we have directly
      visualized the atomic arrangement and Ti vacancies of a titania nanosheet using
      advanced lower-voltage transmission electron microscopy (TEM). Analyses of the
      results of first-principles calculations and TEM image simulations for various Ti
      vacancy structure models indicate that two particular oxygen atoms around each Ti
      vacancy are desorbed, suggesting the sites where atomic reduction first occurs.

PMID- 24077612
TI  - Polymerization of propylene promoted by zirconium benzamidinates.
AB  - New bis(N,N-trimethylsilylarylamidinate) zirconium dichloride complexes with
      various carbon substituents were prepared, and their solid as well as solution
      state structures were studied. In the polymerization of propylene, after
      activation by MAO, these catalysts provided two fractions. Ether soluble polymers
      were obtained at a low activity as sticky polymers with lower molecular weights,
      except with the o-OMe substituted complex. The solid fractions were composed of a
      highly isotactic polymer and a moderately syndiotactic polymer. An interesting
      linear correlation was found between the rates of the 2,1 and 3,1 insertions for
      the ether soluble fractions. 

PMID- 24077613
TI  - Genetic and family and community environmental effects on drug abuse in
      adolescence: a Swedish national twin and sibling study.
AB  - OBJECTIVE: Using Swedish nationwide registry data, the authors investigated
      genetic and environmental risk factors in the etiology of drug abuse by twin
      sibling modeling. The authors followed up with epidemiological analyses to
      identify shared environmental influences on drug abuse. METHOD: Drug abuse was
      defined using public medical, legal, or pharmacy records. Twin and sibling pairs
      were obtained from the national twin and genealogical registers. Information
      about sibling pair residence within the same household, small residential area,
      or municipality was obtained from Statistics Sweden. The authors predicted
      concordance for drug abuse by years of co-residence until the older sibling
      turned 21 and risk for future drug abuse in adolescents living with parental
      figures as a function of family-level socioeconomic status and neighborhood
      social deprivation. RESULTS: The best twin sibling fit model predicted
      substantial heritability for drug abuse in males (55%) and females (73%), with
      environmental factors shared by siblings operating only in males and accounting
      for 23% of the variance in liability. For each year of living in the same
      household, the probability of sibling concordance for drug abuse increased 2%-5%.
      When not residing in the same household, concordance was predicted from residence
      in the same small residential area or municipality. Risk for drug abuse was
      predicted both by family socioeconomic status and neighborhood social
      deprivation. Controlling for family socioeconomic status, each year of living in
      a high social deprivation neighborhood increased the risk for drug abuse by 2%.
      CONCLUSIONS: Using objective registry data, the authors found that drug abuse is
      highly heritable. A substantial proportion of the shared environmental effect on
      drug abuse comes from community-wide rather than household-level influences.
      Genetic effects demonstrated in twin studies have led to molecular analyses to
      elucidate biological pathways. In a parallel manner, environmental effects can be
      followed up by epidemiological studies to clarify social mechanisms.

PMID- 24077614
TI  - Substrate selectivity of high-activity mutants of human butyrylcholinesterase.
AB  - Cocaine is one of the most addictive drugs, and there is still no FDA (Food and
      Drug Administration)-approved medication specific for cocaine abuse. A promising
      therapeutic strategy is to accelerate cocaine metabolism, producing biologically
      inactive metabolites via a route similar to the primary cocaine-metabolizing
      pathway, i.e. cocaine hydrolysis catalyzed by butyrylcholinesterase (BChE) in
      plasma. However, the native BChE has a low catalytic efficiency against the
      abused cocaine, i.e. (-)-cocaine. Our recently designed and discovered
      A199S/F227A/S287G/A328W/Y332G mutant and other mutants of human BChE have a
      considerably improved catalytic efficiency against (-)-cocaine. In the present
      study, we carried out both computational modeling and experimental kinetic
      analysis on the catalytic activities of these promising new BChE mutants against
      other known substrates, including neurotransmitter acetylcholine (ACh),
      acetylthiocholine (ATC), butyrylthiocholine (BTC), and (+)-cocaine, in comparison
      with the corresponding catalytic activity against (-)-cocaine. Both the
      computational modeling and kinetic analysis have consistently revealed that all
      the examined amino acid mutations only considerably improve the catalytic
      efficiency of human BChE against (-)-cocaine, without significantly improving the
      catalytic efficiency of the enzyme against any of the other substrates examined.
      In particular, all the examined BChE mutants have a slightly lower catalytic
      efficiency against neurotransmitter ACh compared to the wild-type BChE. This
      observation gives us confidence in developing an anti-cocaine enzyme therapy by
      using one of these BChE mutants, particularly the A199S/F227A/S287G/A328W/Y332G
      mutant. 

PMID- 24077616
TI  - The role of GluA1 in central nervous system disorders.
AB  - In the brain, the four subunits of the alpha-amino-3-hydroxy-5-methyl-4
      isoxazolepropionic acid (AMPA) receptor, glutamate A1 (GluA1), GluA2, GluA3, and
      GluA4 form functionally different tetramers. Of these, GluA1 is very important.
      It forms calcium-permeable (without GluA2) AMPA receptors and induces the
      trafficking and integration of AMPA receptors within synaptic membranes.
      Increased GluA1 expression and their phosphorylation are common mechanisms for
      the treatment of Alzheimer's disease, schizophrenia, depression, and chronic drug
      addiction. Moreover, GluA1 is also involved in pain and epilepsy. Increased
      phosphorylation of serine831 in the GluA1 receptor is a mechanism necessary to
      alleviate Alzheimer's disease and depression. GluA1-/- knockout mice are used as
      a model of schizophrenia. A decrease in the total cell AMPA receptor currents and
      phosphorylation of serine845 of GluA1 is observed in chronic drug addiction.
      Increased expression of GluA1 causes pain and is involved in epilepsy. GluA1
      promoting AMPA receptor potentiators could be used to treat Alzheimer's disease
      and memory loss. In conclusion, GluA1 agonists or antagonists might be effective
      in various disorders and conditions of the central nervous system that are based
      on GluA1 status at the synaptic region.

PMID- 24077617
TI  - Mechanisms and pathways underlying the therapeutic effect of transcranial
      magnetic stimulation.
AB  - It has been almost 40 years since Barker, Jalinous, and Freeston designed and
      used the first device of transcranial magnetic stimulation (TMS). From then until
      now, this technique has evolved vertiginously, appearing a lot of new protocols
      and device modifications, which associated with new technologies complement and
      enhance the versatility of this technique. TMS has demonstrated to be a safe
      technology and become a key tool in the study of the complex brain processes.
      Despite this, it is as a therapeutic tool where this technique has caused a
      revolution. In this regard, this type of non-invasive brain stimulation has been
      proven useful in a variety of neurodegenerative and psychiatric disorders due to
      its biochemical, molecular, and cellular effects, with depression being the
      paradigm of the therapeutic effectiveness of this technique. This review focuses
      on a detailed vision of how this type of radiation modifies different biochemical
      and cellular processes that induce the mechanisms and pathways underlying the
      therapeutic effects of TMS.

PMID- 24077618
TI  - Baptisms of fire or death knells for acute-slice physiology in the age of 'omics'
      and light?
AB  - With increasing use of various techniques to record optically and
      electrophysiologically from awake behaving animals and the growing developments
      of brain-machine interfaces, one might wonder if the use of acute-slice
      physiology is on its deathbed. Have we actually arrived at a stage where we can
      abandon the use of acute slices, with most of the information about brain
      functions coming from in vivo experiments? We do not believe that this is the
      case, given that our understanding of the nuts and bolts of the nervous system,
      such as ion channels and transporters in near-native state, neuronal
      compartmentalization, and single-neuron computation, is far from complete. We
      believe that in the foreseeable future, questions in these fields will still be
      best addressed by acute-slice physiology. We approach this review from the
      perspective of improving acute-slice physiology so it can continue to provide
      relevant and valuable contributions to neuroscience. We conclude that the death
      of acute-slice physiology is an obituary prematurely written, merely due to
      waxing and waning trends in science and the shortsightedness of investigators.
      Acute-slice physiology has at least one more life to live after the hype around
      new techniques has passed, but it needs to reinvent itself in light of current
      knowledge.

PMID- 24077615
TI  - The role of the actin cytoskeleton in regulating Drosophila behavior.
AB  - Over the past decade, the function of the cytoskeleton has been studied
      extensively in developing and mature neurons. Actin, a major cytoskeletal
      protein, is indispensable for the structural integrity and plasticity of neurons
      and their synapses. Disruption of actin dynamics has significant consequence for
      neurons, neuronal circuits, and the functions they govern. In particular, cell
      adhesion molecules, members of the Rho family of GTPases, and actin-binding
      proteins are important modulators of actin dynamics and neuronal as well as
      behavioral plasticity. In this review, we discuss recent advances in Drosophila
      that highlight the importance of actin regulatory proteins in mediating fly
      behaviors such as circadian rhythm, courtship behavior, learning and memory, and
      the development of drug addiction.

PMID- 24077619
TI  - Brain-computer interface technologies: from signal to action.
AB  - Here, we present a state-of-the-art review of the research performed on the brain
      computer interface (BCI) technologies with a focus on signal processing
      approaches. BCI can be divided into three main components: signal acquisition,
      signal processing, and effector device. The signal acquisition component is
      generally divided into two categories: noninvasive and invasive. For noninvasive,
      this review focuses on electroencephalogram. For the invasive, the review
      includes electrocorticography, local field potentials, multiple-unit activity,
      and single-unit action potentials. Signal processing techniques reviewed are
      divided into time-frequency methods such as Fourier transform, autoregressive
      models, wavelets, and Kalman filter and spatiotemporal techniques such as
      Laplacian filter and common spatial patterns. Additionally, various signal
      feature classification algorithms are discussed such as linear discriminant
      analysis, support vector machines, artificial neural networks, and Bayesian
      classifiers. The article ends with a discussion of challenges facing BCI and
      concluding remarks on the future of the technology.

PMID- 24077620
TI  - Impact of minocycline on neurodegenerative diseases in rodents: a meta-analysis.
AB  - Minocycline is a semisynthetic second-generation tetracycline derivative, and
      many publications provide evidence of its successful neuroprotection in a variety
      of animal models. We searched PubMed and Chinese CNKI databases from January 1992
      to May 2012 for studies on minocycline in neurodegenerative diseases in rodents.
      A meta-analysis that adopted weighted Cohen's d effect sizes, percent overlap,
      Fail-Safe N statistics, and confidence intervals was conducted. In total, 16
      English and 3 Chinese articles with high or medium quality were included in this
      meta-analysis. The treatment benefits for rodents from low-dose (5 mg/kg/day),
      moderate-dose (45, 50, or 55 mg/kg/day), and high-dose (90 mg/kg/day) minocycline
      were larger in Huntington's disease, Alzheimer's disease, and stroke mouse
      models, respectively. In rats, a moderate dose (45 mg/kg/day) of minocycline was
      most effective. In conclusion, minocycline exerts neuroprotective effects in
      rodent models of neurodegenerative diseases. Anti-inflammatory, antiapoptotic,
      and antioxidant activities are discussed as the basis of this effect. However,
      there is insufficient information from these animal models on side effects of
      minocycline therapy.

PMID- 24077621
TI  - Efficient analysis of Q-level nested hierarchical general linear models given
      ignorable missing data.
AB  - This article extends single-level missing data methods to efficient estimation of
      a Q-level nested hierarchical general linear model given ignorable missing data
      with a general missing pattern at any of the Q levels. The key idea is to
      reexpress a desired hierarchical model as the joint distribution of all variables
      including the outcome that are subject to missingness, conditional on all of the
      covariates that are completely observed and to estimate the joint model under
      normal theory. The unconstrained joint model, however, identifies extraneous
      parameters that are not of interest in subsequent analysis of the hierarchical
      model and that rapidly multiply as the number of levels, the number of variables
      subject to missingness, and the number of random coefficients grow. Therefore,
      the joint model may be extremely high dimensional and difficult to estimate well
      unless constraints are imposed to avoid the proliferation of extraneous
      covariance components at each level. Furthermore, the over-identified
      hierarchical model may produce considerably biased inferences. The challenge is
      to represent the constraints within the framework of the Q-level model in a way
      that is uniform without regard to Q; in a way that facilitates efficient
      computation for any number of Q levels; and also in a way that produces unbiased
      and efficient analysis of the hierarchical model. Our approach yields Q-step
      recursive estimation and imputation procedures whose qth-step computation
      involves only level-q data given higher-level computation components. We
      illustrate the approach with a study of the growth in body mass index analyzing a
      national sample of elementary school children.

PMID- 24077622
TI  - Young adults on disability benefits in 7 countries.
AB  - BACKGROUND: This article, based on a study by the Swedish Social Insurance
      Inspectorate, describes the development of young adults receiving disability
      benefits due to reduced working capability, and the disability benefit systems in
      seven European countries; Denmark, Finland, Iceland, Norway, the Netherlands,
      Sweden, and the UK. This comparative study mainly uses Sweden as a benchmark.
      METHODS: Apart from a documentary and legal data collection and analysis, 26 semi
      structured interviews were conducted with representatives of the responsible
      ministries and authorities in the studied countries. In addition, national and
      European data was collected. RESULTS: There is an increasing trend of young
      adults, aged 19-29, on disability benefits in all studied countries. The most
      common diagnosis group among young adults on disability benefits is mental and
      behavioural disorders, ranging from 58% in the UK to 80% in Denmark. CONCLUSIONS:
      The comparison of the different disability benefit systems shows that there are
      relatively large national differences in terms of rules and regulations, the
      handling of disability benefit cases, and offered rehabilitation activities and
      other measures to support young adults on disability benefits to strengthen their
      working capability, and hence enable them to approach the labour market in the
      future. However, it is clear that these countries face similar challenges, and
      therefore there could be a lot to learn from European exchange of experiences and
      expertise in this area. This article identifies a number of measures of special
      interest to study and discusses further with regard to the further development of
      the Swedish system for disability benefits for young adults.

PMID- 24077623
TI  - [Definition, diagnosis, and prevalence of occult hepatitis B virus infection].
AB  - Occult HBV infection is characterized by the absence of serum HBsAg with
      persistence of low level of intrahepatic HBV DNA. Several suggested mechanisms
      for the origin of occult HBV infection include strong suppression of viral
      replication and gene expression, mutation in the regulatory regions of HBV
      genome, formation of immunoglobulin-bound HBsAg, viral interference, and blockage
      of HBsAg secretion from infected hepatocytes. Standardized assays are not yet
      available, and sensitive HBV DNA amplification assay is necessary for the
      diagnosis of cryptic infection. Detection rate of HBV DNA is highest in IgG anti
      HBc positive population. However, neither anti-HBc nor anti-HBs can be detected
      in a significant proportion of infected persons. Occult HBV infection occurs in a
      number of clinical settings and is highly prevalent in HCV-infected patients as
      well as in patients with cryptogenic chronic liver disease including
      hepatocellular carcinoma.

PMID- 24077624
TI  - [Occult hepatitis B virus infection: transmission and reactivation].
AB  - Occult HBV infection (OBI) is defined as presence of HBV DNA in the liver tissue
      in patients with serologically undetectable HBsAg. There are differences in
      virologic and serological profiles of OBI. Majority of OBI are positive for anti
      HBs and/or anti-HBc and minor portion are negative for all HBV markers. However,
      there are no HBV mutations in the surface and its regulatory regions. HBV
      infection persists by the presence of covalently closed circular DNA (cccDNA)
      within the infected hepatocytes, which serves as a reservoir for future
      infection. OBI increases the risk of HBV transmission through transfusion,
      hemodialysis, and organ transplantation. Therefore effective measures should be
      employed to screen OBI. Antiviral therapy is needed in HBsAg-negative transplant
      patients who are anti-HBc positive to prevent the recurrence of HBV infection.
      Since HBV replication is strongly suppressed by immune surveillance system in OBI
      patients, immunosuppression results in massive HBV replication. This leads to
      acute hepatitis and sometimes mortality when immune surveillance is recovered
      after stopping immunosuppressive drugs/anticancer chemotherapy. Therefore, narrow
      surveillance is required to recognize the viral reactivation and start antiviral
      agents during immunosuppressive therapy/anticancer chemotherapy in patients with
      OBI.

PMID- 24077625
TI  - [Occult hepatitis B virus infection in chronic hepatitis C].
AB  - Occult HBV infection is defined as the presence of HBV DNA in the liver (with or
      without detectable or undetectable HBV DNA in the serum) of individuals testing
      negative for HBsAg. Studies on occult HBV infection in hepatitis C patients have
      reported highly variable prevalence, because the prevalence of occult HBV
      infection varies depending on the hepatitis B risk factors and methodological
      approaches. The most reliable diagnostic approach for detecting occult HBV
      detection is through examination of liver DNA extracts. HCV has been suspected to
      strongly suppress HBV replication up to the point where it may be directly
      responsible for occult HBV infection development. However, more data are needed
      to arrive at a definitive conclusion regarding the role of HCV in inducing occult
      HBV infection. Occult HBV infection in chronic hepatitis C patients is a complex
      biological entity with possible relevant clinical implications. Influence of
      occult HBV infection on the clinical outcomes of chronic hepatitis C may be
      considered negative. However, recent studies have shown that occult HBV infection
      could be associated with the development of hepatocellular carcinoma and
      contribute to the worsening of the course of chronic liver disease over time in
      chronic hepatitis C patients. Nevertheless, the possible role of occult HBV
      infection in chronic hepatitis C is still unresolved and no firm conclusion has
      been made up until now. It still remains unclear how occult HBV infection affects
      the treatment of chronic hepatitis C. Therefore, in order to resolve current
      controversies and understand the pathogenic role and clinical impacts of occult
      HBV infection in chronic hepatitis C patients, well-designed clinical studies are
      needed.

PMID- 24077626
TI  - [Occult hepatitis B virus infection and hepatocellular carcinoma].
AB  - Many studies have suggested that occult HBV infection has a substantial clinical
      relevance to hepatocellular carcinoma (HCC). Occult HBV infection is an important
      risk factor for the development of cirrhosis and HCC in patients without HBsAg.
      As a matter of fact, occult HBV infection is one of the most common causes of
      crytogenic HCC in endemic areas of HBV. However, there still are controversial
      issues about the association between occult HBV infection and HCC according to
      the underlying liver disease. In alcoholic cirrhosis, occult HBV infection may
      exert synergistic effect on the development of HCC. However, there is
      insufficient evidence to relate occult HBV infection to hepatocarcinogenesis in
      non-alcoholic fatty liver disease. In cryptogenic HCC, occult HBV infection may
      play a direct role in the development of HCC. In order to elucidate the
      assocciation between occult HBV infection and HCC, underlying liver disease must
      be specified and larger number of cases must be included in future studies.

PMID- 24077627
TI  - A case of a jejunal ectopic pancreas presenting as obscure gastrointestinal
      bleeding.
AB  - A jejunal ectopic pancreas, where pancreatic tissue is found outside of the usual
      anatomical location, is a rare submucosal tumor that may cause obscure
      gastrointestinal (GI) bleeding. After initial negative endoscopic evaluation of
      the obscure GI bleeding, including colonoscopy and/or upper endoscopy, it is
      reasonable to proceed with further evaluation of the small bowel. Diagnostic
      options for the evaluation of the small bowel may include capsule endoscopy, push
      enteroscopy, or barium contrast small bowel studies. Here, we report a case of
      obscure GI bleeding caused by a jejunal ectopic pancreas, diagnosed through
      capsule endoscopy and barium contrast small bowel studies, which was treated
      successfully with single incision access laparoscopy.

PMID- 24077628
TI  - A rare case of free bowel perforation associated with infliximab treatment for
      stricturing Crohn's disease.
AB  - Crohn's disease is characterized by chronic transmural inflammation of the bowel
      and is associated with serious complications, such as bowel strictures,
      abscesses, fistula formation, and perforation. As neither medical nor surgical
      therapy provides a cure for Crohn's disease, the primary goals of therapy are to
      induce and maintain remission and prevent complications. As a biologic agent,
      infliximab, a monoclonal antibody to tumor necrosis factor, is indicated for
      refractory luminal and fistulizing Crohn's disease that does not respond to other
      medical therapies or surgery. Infliximab has proven to be very effective for
      inducing and maintaining remission in Crohn's disease; however, infliximab
      treatment has several potential complications. Here, we report a case of free
      perforation following a therapeutic response after an initial dose of infliximab
      for Crohn's disease. This is the first case report describing a free perforation
      in a Crohn's disease patient after an initial dose of infliximab.

PMID- 24077629
TI  - A case of diaphragmatic hernia induced by radiofrequency ablation for
      hepatocellular carcinoma.
AB  - Because of its safety and treatment effectiveness, the popularity of
      radiofrequency ablation (RFA) for the treatment of hepatocellular carcinoma (HCC)
      has gradually increased. However, some serious complications of RFA such as
      hepatic infarction, bowel perforation, and tumor seeding have been reported.
      Recently, we experienced a case of diaphragmatic hernia after RFA for HCC. A 61
      year-old man with alcoholic cirrhosis was diagnosed with a 1.0 cm sized HCC in
      segment (S) 5 and a 1.3 cm sized HCC in S 8 of the liver. He was treated by
      transarterial chemoembolization and RFA. After RFA, an abdominal CT revealed a
      diaphragmatic defect with herniating mesentery. Twenty-two months after the RFA,
      the chest CT showed the diaphragmatic defect with herniating colon and mesentery.
      Because he had no symptoms, and surgical repair for the diaphragmatic hernia
      would be a high risk operation for him, we decided to treat the patient
      conservatively. For its great rarity, we report this case with a review of the
      literature.

PMID- 24077630
TI  - [A case of spontaneous bacterial peritonitis caused by Listeria monocytogenes].
AB  - Spontaneous bacterial peritonitis (SBP) is a life-threatening complication in
      patients with ascites caused by advanced liver disease. While gram negative
      bacteria, such as Escherichia coli and Klebsiella pneumonia are the common
      pathogens, Listeria monocytogenes has been recognized as a very rare pathogen.
      Empirical treatment with third generation cephalosporins does not provide
      adequate antibiotics coverage against L. monocytogenes. Diagnosis is often
      delayed as it requires confirmation from ascitic fluid culture. Herein, we
      describe the first case of SBP caused by L. monocytogenes in a patient with
      advanced alcoholic liver cirrhosis in Korea. Clinicians should be aware of the
      atypical pathogens, especially in patients with inadequate response to empirical
      antibiotics.

PMID- 24077631
TI  - In vitro functional characterization of 37 CYP2C9 allelic isoforms found in
      Chinese Han population.
AB  - AIM: Cytochrome P450 2C9 (CYP2C9) is a polymorphic enzyme that is responsible for
      the metabolism of approximately 15% of clinically important drugs. The aim of
      this study was to assess the catalytic characteristics of 37 CYP2C9 allelic
      isoforms found in Chinese Han population on the metabolism of tolbutamide in
      vitro. METHODS: The wild-type and 36 CYP2C9 variants were expressed in sf21
      insect cells using a baculovirus-mediated expression system. Then the insect
      microsomes were prepared for assessing the metabolic characteristics of each
      variant toward the CYP2C9-specific drug substrate tolbutamide. RESULTS: Of 36
      allelic variants tested, the intrinsic clearance values of 2 allelic isoforms
      (CYP2C9.36 and CYP2C9.51) were much higher than the wild-type CYP2C9.1 protein, 3
      allelic isoforms (CYP2C9.11, CYP2C9.56 and N418T) exhibited similar intrinsic
      clearance values as the wild-type enzyme, whereas the other 31 variants showed
      significantly reduced intrinsic clearance values, ranging from 0.08% to 66.88%,
      for tolbutamide. CONCLUSION: Our study provides the most comprehensive data
      concerning the enzymatic activity of the CYP2C9 variants that are present in the
      Chinese Han population, and our data suggest that most of the carriers of these
      alleles might be paid more attention when using CYP2C9 mediated drugs clinically.

PMID- 24077632
TI  - Benzbromarone, an old uricosuric drug, inhibits human fatty acid binding protein
      4 in vitro and lowers the blood glucose level in db/db mice.
AB  - AIM: Fatty acid-binding protein 4 (FABP4) plays an important role in maintaining
      glucose and lipid homeostasis. The aim of this study was to find new inhibitors
      of FABP4 for the treatment of type 2 diabetes. METHODS: Human FABP4 protein was
      expressed, and its inhibitors were detected in 1,8-ANS displacement assay. The
      effect of the inhibitor on lipolysis activity was examined in mouse 3T3-L1
      preadipocytes. The db/db mice were used to evaluate the anti-diabetic activity of
      the inhibitor. Molecular docking and site-directed mutagenesis studies were
      carried out to explore the binding mode between the inhibitor and FABP4. RESULTS:
      From 232 compounds tested, benzbromarone (BBR), an old uricosuric drug, was
      discovered to be the best inhibitor of FABP4 with an IC50 value of 14.8 MUmol/L.
      Furthermore, BBR (25 MUmol/L) significantly inhibited forskolin-stimulated
      lipolysis in 3T3-L1 cells. Oral administration of BBR (25 or 50 mg/kg, for 4
      weeks) dose-dependently reduced the blood glucose level and improved glucose
      tolerance and insulin resistance in db/db mice. Molecular docking revealed that
      the residues Ser55, Asp76, and Arg126 of FABP4 formed important interactions with
      BBR, which was confirmed by site-directed mutagenesis studies. CONCLUSION: BBR is
      an inhibitor of FABP4 and a potential drug candidate for the treatment of type 2
      diabetes and atherosclerosis.

PMID- 24077633
TI  - Sodium tanshinone IIA sulfonate protects rat myocardium against ischemia
      reperfusion injury via activation of PI3K/Akt/FOXO3A/Bim pathway.
AB  - AIM: To investigate the mechanisms underlying the protective effects of sodium
      tanshinone IIA sulfonate (STS) in an ischemia-reperfusion (I/R)-induced rat
      myocardial injury model. METHODS: Male SD rats were iv injected with STS,
      STS+LY294002 or saline (NS) for 15 d. Then the hearts were subjected to 30 min of
      global ischemia followed by 2 h of reperfusion. Cardiac function, infarction size
      and area at risk were assessed. Cell apoptosis was evaluated with TUNEL staining,
      DNA laddering and measuring caspase-3 activity. In addition, isolated
      cardiomyocytes of neonatal rats were pretreated with the above drugs, then
      exposed to H2O2 (200 mol/L) for 1 h. Cell apoptosis was detected using flow
      cytometric assay. The levels of p-Akt, p-FOXO3A and Bim were examined with
      immunoblotting. RESULTS: Compared to NS group, administration of STS (20 mg/kg)
      significantly reduced myocardial infarct size (40.28%+/-5.36% in STS group vs
      59.52%+/-7.28% in NS group), and improved the myocardial function as demonstrated
      by the increased values of dp/dtmax, LVDP and coronary flow at different
      reperfusion time stages. Furthermore, STS significantly decreased the rate of
      apoptotic cells (15.11%+/-3.71% in STS group vs 38.21%+/-7.83% in NS group), and
      reduced caspase-3 activity to nearly a quarter of that in NS group. Moreover, STS
      significantly increased the phosphorylation of Akt and its downstream target
      FOXO3A, and decreased the expression of pro-apoptotic gene Bim. Co-treatment with
      the PI3K inhibitor LY294002 (40 mg/kg) partially countered the protective effects
      induced by STS treatment. In isolated cardiomyocytes, STS exerted similar
      protective effects as shown in the ex vivo I/R model. CONCLUSION: STS
      pretreatment reduces infarct size and improves cardiac function in an I/R-induced
      rat myocardial injury model via activation of Akt/FOXO3A/Bim-mediated signal
      pathway.

PMID- 24077634
TI  - Punicalagin induces apoptotic and autophagic cell death in human U87MG glioma
      cells.
AB  - AIM: To investigate the effects of punicalagin, a polyphenol isolated from Punica
      granatum, on human U87MG glioma cells in vitro. METHODS: The viability of human
      U87MG glioma cells was evaluated using MTT assay. Cell cycle was detected with
      flow cytometry analysis. The levels of Bcl-2, cleaved caspase-9, cleaved poly(ADP
      ribose) polymerase (PARP), phosphor-AMPK and phosphor-p27 at Thr198 were measured
      using immunoblot analyses. Caspase-3 activity was determined with
      spectrophotometer. To determine autophagy, LC3 cleavage and punctate patterns
      were examined. RESULTS: Punicalagin (1-30 MUg/mL) dose-dependently inhibited the
      cell viability in association with increased cyclin E level and decreased cyclin
      B and cyclin A levels. The treatment also induced apoptosis as shown by the
      cleavage of PARP, activation of caspase-9, and increase of caspase-3 activity in
      the cells. However, pretreatment of the cells with the pan-caspase inhibitor z
      DEVD-fmk (50 MUmol/L) did not completely prevent the cell death. On the other
      hand, punicalagin treatment increased LC3-II cleavage and caused GFP-LC3-II
      stained punctate pattern in the cells. Suppressing autophagy of cells with
      chloroquine (1-10 MUmol/L) dose-dependently alleviated the cell death caused by
      punicalagin. Punicalagin (1-30 MUg/mL) also increased the levels phosphor-AMPK
      and phosphor-p27 at Thr198 in the cells, which were correlated with the induction
      of autophagic cell death. CONCLUSION: Punicalagin induces human U87MG glioma cell
      death through both apoptotic and autophagic pathways.

PMID- 24077635
TI  - Ethnicity, socioeconomic position and severity of problems as predictors of
      mental health care use in 5- to 8-year-old children with problem behaviour.
AB  - BACKGROUND: Empirical research on mental health care use and its determinants in
      young school-aged children is still scarce. In this study, we investigated the
      role of ethnicity, socioeconomic position (SEP) and perceived severity by both
      parents and teachers on mental health care use in 5- to 8-year old children with
      emotional and/or behavioural problems. METHODS: Data from 1,269 children with a
      high score([P90) on the Strengths and Difficulties Questionnaire (SDQ) in the
      school year 2008-2009 were linked to psychiatric case register data over the
      years 2010-2011. Cox proportional hazards models were used to predict mental
      health care use from ethnicity, SEP and perceived severity of the child's
      problems. RESULTS: During the follow-up period, 117 children with high SDQ scores
      (9.2 %) had used mental health care for the first time. Ethnic minority children
      were less likely to receive care than Dutch children (HR Moroccan/Turkish:0.26;
      95 % CI 0.13-0.54, HR other ethnicity: 0.26; 95 %CI 0.12-0.58). No socioeconomic
      differences were found.After correction for previous care use, ethnicity and
      parental perceived severity, impact score as reported by teachers was
      significantly associated with mental healthcare use (HR 1.58; 95 % CI 1.01-2.46).
      CONCLUSIONS: Ethnicity is an important predictor of mental health care use in
      young children. Already in the youngest school-aged children, ethnic differences
      in the use of mental health care are present.A distinct predictor of care use in
      this age group is severity of emotional and behavioural problems as perceived by
      teachers. Therefore, teachers may be especially helpful in the process of
      identifying young children who need specialist mental health care.

PMID- 24077636
TI  - First-day iodine kinetics is useful for individualizing radiation safety
      precautions for thyroid carcinoma patients.
AB  - OBJECTIVE: There is considerable variation in the national regulations of
      different countries for the release of patients from hospitals after radioiodine
      therapy. Individual variations make these practices, when based on the worst case
      scenarios, too restrictive for the majority of patients. However, there are cases
      in which strict rules are needed to comply with the dose limits to other
      individuals, especially children. We have developed a method to individualize
      radiation safety precautions. MATERIALS AND METHODS: Twenty-three patients with
      differentiated thyroid carcinoma were included in the study. Four weeks after
      thyroidectomy, 1.1-3.7 GBq of radioiodine was administered and iodine kinetics
      were followed with external measurements until hospital discharge. The absorbed
      dose at the wrist holder was measured with thermoluminescence dosimetry (TLD)
      during hospital stay and after hospital discharge for up to 1 week. The TLD
      results were compared with the iodine kinetics. The dose to other individuals was
      estimated with extra TLDs located both on the patient's bed and given to family
      members. The kinetics data were fitted in both monoexponential and biexponential
      models and both for the full measurement period (down to the residual activity
      level<400 MBq) and for the first 24 h after radioiodine administration. RESULTS:
      The biexponential model was capable of predicting the cumulated dose up to 1 week
      for both the longer and the shorter measured data set. The occupancy factors both
      for a person sleeping on the same bed and for a person living in the same
      apartment with the patient were in agreement with the recommended occupancy
      factor values of the American Thyroid Association. From these findings it is
      possible to individualize radiation safety precautions by taking into account the
      iodine pharmacokinetics and living conditions of a patient. CONCLUSION: By
      measuring the activity content within the body for the first 24 h after
      radioiodine administration it is possible to individualize radiation safety
      precautions for thyroid carcinoma patients.

PMID- 24077637
TI  - Nabothian cyst associated with high false-positive incidence of iodine-131 uptake
      in whole-body scans after treatment for differentiated thyroid cancer.
AB  - OBJECTIVE: This study aimed to analyze the focal uptake of iodine-131 (131I) in
      the upper pelvis superior to the urinary bladder on whole-body images of patients
      who underwent this treatment after thyroidectomy for differentiated thyroid
      cancer. METHODS: Between June 2012 and March 2013, 205 patients (72 men and 133
      women, with an average age of 47.9 +/- 11.7 years) who underwent 131I radioactive
      treatment after thyroid cancer surgery were analyzed retrospectively.
      Pathological findings confirmed papillary thyroid carcinoma. A whole-body scan
      was acquired 5 days after 100-120 mCi sodium iodide was administered orally to
      the patients. Single-photon emission computed tomography/computed tomography
      (SPECT/CT) scanning was carried out to locate the lesion; this showed abnormal
      intense activity in the upper pelvis superior to the urinary bladder, which was
      further evaluated by ultrasonography. RESULTS: Using 131I-SPECT scanning, five
      (3.76%) female patients were shown to have abnormal focal radioactivity in the
      lower abdomen. Subsequent SPECT/CT examination showed that the radioactivity was
      located in the cervix in four of the five patients and in the sigmoid colon in
      one patient. Transvaginal ultrasonography was performed in the former four
      patients, which revealed several echo-free regions in the cervix. These findings
      are consistent with the diagnosis of a nabothian cyst. Three of these patients
      were administered a second course of radioiodine therapy. Radioactive uptake was
      still visible at the same sites on whole-body imaging. CONCLUSION: Nabothian cyst
      should be considered in cases in which abnormal uptake in the upper pelvis
      superior to the urinary bladder is detected on 131I whole-body scans after
      differentiated thyroid cancer resection.

PMID- 24077638
TI  - Cyclometalated platinum(II) with ethynyl-linked azobenzene ligands: an original
      switching mode.
AB  - The photophysical properties of 6-phenyl-2,2'-bipyridyl platinum(ii) complexes
      bearing different sigma-alkynyl-linked azobenzene ancillary ligands were
      investigated. These complexes exhibited strong, broad, structureless charge
      transfer bands in the visible region, which were red-shifted when the electron
      donating ability of the para substituent on the azo-acetylide ligand increased.
      When excited at the charge-transfer absorption band, the complexes exhibited weak
      green emission, which was assigned to a triplet metal-to-ligand charge
      transfer/interligand charge transfer emission ((3)MLCT/(3)L'LCT). The presence of
      an amino substituent in the azobenzene moiety opened the possibility of
      protonation, which led to the formation of an azonium based derivative and
      resulted in drastic perturbations of the molecular orbitals and photophysical
      properties of the Pt-acetylide complex. These studies are fully supported by DFT
      and TD-DFT calculations. 

PMID- 24077640
TI  - On the Effect of Preferential Sampling in Spatial Prediction.
AB  - The choice of the sampling locations in a spatial network is often guided by
      practical demands. In particular, many locations are preferentially chosen to
      capture high values of a response, for example, air pollution levels in
      environmental monitoring. Then, model estimation and prediction of the exposure
      surface become biased due to the selective sampling. Since prediction is often
      the main utility of the modeling, we suggest that the effect of preferential
      sampling lies more importantly in the resulting predictive surface than in
      parameter estimation. Our contribution is to offer a direct simulation-based
      approach to assessing the effects of preferential sampling. We compare two
      predictive surfaces over the study region, one originating from the notion of an
      'operating' intensity driving the selection of monitoring sites, the other under
      complete spatial randomness. We can consider a range of response models. They may
      reflect the operating intensity, introduce alternative informative covariates, or
      just propose a flexible spatial model. Then, we can generate data under the given
      model. Upon fitting the model and interpolating (kriging), we will obtain two
      predictive surfaces to compare. It is important to note that we need suitable
      metrics to compare the surfaces and that the predictive surfaces are random, so
      we need to make expected comparisons.

PMID- 24077639
TI  - 'Keller & Barnes' after 5 years - still inadmissible as evidence.

PMID- 24077641
TI  - Who has housing affordability problems? Disparities in Housing Cost burden by
      Race, Nativity and Legal Status in Los Angeles.
AB  - Housing costs are a substantial component of U.S. household expenditures. Those
      who allocate a large proportion of their income to housing often have to make
      difficult financial decisions with significant short-term and long-term
      implications for adults and children. This study employs cross-sectional data
      from the first wave of the Los Angeles Family and Neighborhood Survey (L.A.FANS)
      collected between 2000 and 2002 to examine the most common U.S. standard of
      housing affordability, the likelihood of spending thirty percent or more of
      income on shelter costs. Multivariate analyses of a low-income sample of U.S.
      born Latinos, Whites, African Americans, authorized Latino immigrants and
      unauthorized Latino immigrants focus on baseline and persistent differences in
      the likelihood of being cost burdened by race, nativity and legal status. Nearly
      half or more of each group of low-income respondents experience housing
      affordability problems. The results suggest that immigrants' legal status is the
      primary source of disparities among those examined, with the multivariate
      analyses revealing large and persistent disparities for unauthorized Latino
      immigrants relative to most other groups. Moreover, the higher odds of housing
      cost burden observed for unauthorized immigrants compared with their authorized
      immigrant counterparts remains substantial, accounting for traditional indicators
      of immigrant assimilation. These results are consistent with emerging scholarship
      regarding the role of legal status in shaping immigrant outcomes in the United
      States.

PMID- 24077642
TI  - Combining Surface Treatments with Shallow Slots to Improve the Spatial Resolution
      Performance of Continuous, Thick LYSO Detectors for PET.
AB  - Positron emission tomography (PET) detectors based on continuous scintillation
      crystals can achieve very good performance and have a number of practical
      advantages compared to detectors based on a pixelated array of crystals. Our goal
      is to develop a thick continuous detector with high energy and spatial
      resolution, along with high gamma-photon capture efficiency. We examine the
      performance of two crystal blocks: a 46 * 46 * 14 mm3 and a 48 * 48 * 25 mm3
      block of LYSO (Lutetium Yttrium Orthosilicate). Using Maximum Likelihood (ML)
      positioning based upon the light response function (LRF) in the 14 mm thick
      crystal, we measure a spatial resolution of 3 mm in the central region of the
      crystal with degradation near the edges due to reflections off the crystal sides.
      We also show that we can match the spatial resolution achieved using a 14 mm
      thick crystal by using a 25 mm thick crystal with slots cut into the gamma
      entrance surface to narrow the LRF. We also find that we can improve the spatial
      resolution performance near the detector edges by reducing the reflectivity of
      the crystal sides, albeit with some loss in energy resolution.

PMID- 24077643
TI  - Patient personality and therapist response: an empirical investigation.
AB  - OBJECTIVE: The aim of this study was to examine the relationship between
      therapists' emotional responses and patients' personality disorders and level of
      psychological functioning. METHOD: A random national sample of psychiatrists and
      clinical psychologists (N=203) completed the Therapist Response Questionnaire to
      identify patterns of therapists' emotional response, and the Shedler-Westen
      Assessment Procedure-200 to assess personality disorders and level of
      psychological functioning in a randomly selected patient currently in their care
      and with whom they had worked for a minimum of eight sessions and a maximum of 6
      months (one session per week). RESULTS: There were several significant
      relationships between therapists' responses and patients' personality pathology.
      Paranoid and antisocial personality disorders were associated with
      criticized/mistreated countertransference, and borderline personality disorder
      was related to helpless/inadequate, overwhelmed/disorganized, and
      special/overinvolved countertransference. Disengaged countertransference was
      associated with schizotypal and narcissistic personality disorders and negatively
      associated with dependent and histrionic personality disorders. Schizoid
      personality disorder was associated with helpless/inadequate responses. Positive
      countertransference was associated with avoidant personality disorder, which was
      also related to both parental/protective and special/overinvolved therapist
      responses. Obsessive-compulsive personality disorder was negatively associated
      with special/overinvolved therapist responses. In general, therapists' responses
      were characterized by stronger negative feelings when working with lower
      functioning patients. CONCLUSIONS: Patients' specific personality pathologies are
      associated with consistent emotional responses, which suggests that clinicians
      can make diagnostic and therapeutic use of their responses to patients.

PMID- 24077644
TI  - To kiss or not to kiss? Impact of final kissing-balloon inflation  on early and
      long-term results of percutaneous coronary  intervention for bifurcation lesions.
AB  - Final kissing-balloon inflation is often recommended for percutaneous coronary
      intervention (PCI) of bifurcation lesions. However, randomized trials focusing on
      kissing inflation have not confirmed its beneficial impact. We compared outcomes
      of kissing inflation for PCI of bifurcation lesions, explicitly stratifying
      results according to stenting strategy. Patients undergoing bifurcation PCI were
      retrospectively enrolled. Subjects receiving final kissing inflation were
      compared with those not undergoing kissing inflation, after stratification for a
      single-stent technique. The primary end point was the long-term rate of major
      adverse cardiac events (MACE, i.e., death, myocardial infarction, or target
      lesion revascularization (TLR)). A total of 4314 patients were included: 1176
      (27.3 %) treated with a single stent and kissing inflation, 1637 (37.9 %) with a
      single stent but no kissing, 1072 (24.8 %) with two stents and kissing, and 429
      (9.9 %) with two stents but no kissing. At unadjusted analyses kissing was
      associated with fewer short-term MACE and deaths in the two-stent group, and with
      fewer long-term MACE, cardiac deaths, and side-branch TLR in the two-stent group
      (all P < 0.05). Conversely, kissing appeared detrimental after single stenting.
      However, after multivariable analyses, kissing no longer significantly affected
      the risk of adverse events, with the exception of the risk of side-branch TLR,
      which was lower in those receiving two stents and final kissing inflation (hazard
      ratio = 0.52, 95 % confidence interval 0.30-0.90, P = 0.020). Kissing inflation
      can be avoided in bifurcation lesions uneventfully treated with single-stent PCI.
      However, final kissing-balloon inflation appears beneficial in reducing the risk
      of side-branch repeat revascularization after using a two-stent strategy.

PMID- 24077645
TI  - Adolescent blood pressure hyperreactors have a higher reactive hyperemic index at
      the fingertip.
AB  - PURPOSE: The use of peripheral arterial tonometry (PAT) to assess microvascular
      endothelial function is getting increasingly popular in the pediatric population.
      The aim of the present study was to examine the impact of blood pressure (BP)
      hyperreactivity on microvascular hyperemic reaction in healthy, normotensive
      adolescents. METHODS: Fifty-two adolescents with a mean age of 14.5 +/- 0.7 years
      were investigated. Microvascular endothelial function was assessed at rest and
      after exhaustive cycling exercise using PAT to determine the reactive hyperemic
      index (RHI, primary endpoint). Hyperreactors were identified according to their
      cardiovascular response to a cold pressor test. Indices of autonomic tone were
      assessed with an ambulatory electrocardiograph and cardiopulmonary exercise
      testing was performed on a cycle ergometer. Physical activity was measured using
      accelerometry. ANOVA with repeated measures and Tukey HSD post hoc tests were
      applied to determine differences between BP hyperreactors and controls (normal
      reactors). RESULTS: Sixteen adolescents were identified as hyperreactors and
      matched with regard to age, sex, pubertal status, and height with 16 normal
      reactors. At rest, hyperreactors had a significantly higher RHI than normal
      reactors (2.1 +/- 0.4 vs. 1.6 +/- 0.4, P = 0.003). After exhaustive cycling
      exercise, the differences in RHI were abolished. No differences between these two
      groups existed in physical activity levels, exercise capacity and indices of
      autonomic tone. CONCLUSIONS: Our data suggest that normotensive hyperreactors
      have a markedly higher RHI compared to normal reactors. Future studies using PAT
      to assess microvascular endothelial function should bare in mind the large effect
      of vascular hyperreactivity.

PMID- 24077647
TI  - Carotid intima media thickness, oxidative stress, and inflammation in children
      with chronic kidney disease.
AB  - OBJECTIVE: We evaluated the association between inflammation and oxidative stress
      with carotid intima media thickness (cIMT) and elasticity increment module
      (E(inc)) in pediatric patients with chronic kidney disease (CKD). METHODS: This
      analytical, cross-sectional study assessed 134 children aged 6-17 years with CKD.
      Anthropometric measurements and biochemistry of intact parathyroid hormone
      (iPTH), high-sensitivity C-reactive protein (CRP), interleukin (IL)-6, IL-1beta,
      reduced glutathione (GSH), malondialdehyde, nitric oxide, and homocysteine were
      recorded. Bilateral carotid ultrasound (US) was taken. Patients were compared
      with controls for cIMT and E(inc) using >= 75 percentile (PC). RESULTS: Mean cIMT
      was 0.528 +/- 0.089 mm; E(inc) was 0.174 +/- 0.121 kPa * 10(3); cIMT negatively
      correlated with phosphorus (r -0.19, p =0.028) and the calcium * phosphorus (Ca *
      P) product (r -0.26, p =0.002), and positively with iPTH (r 0.19,p =0.024). After
      adjusting for potential confounders, hemodialysis (HD) (beta=0.111, p =<0.001),
      automated peritoneal dialysis (APD) (beta=0.064, p =0.026), and Ca x P
      product(beta=-0.002, p =0.015) predicted cIMT (R(2)=0.296). In patients on
      dialysis, HD (beta=0.068, p =0.010), low-density lipoprotein cholesterol (LDL-C)
      (beta=0.001, p =0.048), and GSH(beta=-0.0001, p=0.041) independently predicted
      cIMT (R(2)=0.204); HD, hypoalbuminemia, and high iPTH increased the risk of
      increased cIMT. In dialysis, E(inc) was inversely associated with GSH, and in
      predialysis, Ca * P correlated with/predicted E(inc) (beta=0.001, p =0.009).
      CONCLUSIONS: cIMT and E(inc) strongly associate with several biochemical
      parameters and GSH but not with other oxidative stress or inflammation markers.

PMID- 24077648
TI  - SASP: roadblock for tissue re-organization.

PMID- 24077649
TI  - Ultrasonographic evaluation of calcification patterns in costal cartilage:
      implications for rib graft harvesting.
AB  - IMPORTANCE: Complex augmentation rhinoplasty often requires the use of
      cartilaginous grafts, especially in revision surgery. When using costal
      cartilage, the possibility of inadequate cartilage material because of excessive
      calcification must always be kept in mind. Furthermore, cartilage may be
      harvested but found to be not ideal, causing unsatisfying results. OBJECTIVE: To
      report our experience with the use of preoperative ultrasonographic (US)
      examinations for quality analysis of costal cartilage. DESIGN, SETTING, AND
      PARTICIPANTS: In an academic research setting, US imaging of the anterior rib
      cage was performed before 83 revision rhinoplasties requiring costal cartilage
      grafting. MAIN OUTCOMES AND MEASURES: Cartilage volume, quality, sex-specific
      calcification patterns, and the location of hidden calcification islands within
      viable cartilage were recorded. RESULTS: Two different calcification patterns, 1
      central and 1 peripheral, were identified. CONCLUSIONS AND RELEVANCE: We found
      this cost-effective technique to be a valuable tool for easy preoperative
      cartilage assessment. Furthermore, US screening guides the surgeon to areas of
      harvestable cartilage and to cartilage that is best suited for rhinoplasty in
      terms of distribution patterns of calcification areas. LEVEL OF EVIDENCE: NA.

PMID- 24077650
TI  - MIGRATION, WAR, AND THE MAKING OF A TRANSNATIONAL LEBANESE SHI'I COMMUNITY IN
      SENEGAL.

PMID- 24077651
TI  - Arsenic exposure affects embryo development of sea urchin, Paracentrotus lividus
      (Lamarck, 1816).
AB  - Toxicity tests were performed with embryos of Paracentrotus lividus to
      investigate the toxicological effect of two arsenic species: arsenate (As(V)),
      expected to be more toxic, and dimethyl-arsinate (DMA) expected to be less toxic.
      Exposures to toxicants were performed at different developmental stages in order
      to identify the most sensitive phase of embryological development. Statistical
      analysis revealed a high significance of each factor (Molecule, Concentration and
      Time of exposure) and their interaction for the dependent variable "Percentage of
      normal-shaped plutei". In particular, the 8 cell stage was the most sensitive to
      arsenic; at a concentration of 50 MUg L(-1) DMA proved to be more toxic than
      As(V), resulting in nearly 50 % of normal-shaped plutei against the 74 % recorded
      for As(V). Starting the administration of arsenic at the morula stage, arsenate
      proved to be significantly more toxic when compared to DMA.

PMID- 24077652
TI  - Spatial variation in the bacterial and denitrifying bacterial community in a
      biofilter treating subsurface agricultural drainage.
AB  - Denitrifying biofilters can remove agricultural nitrates from subsurface
      drainage, reducing nitrate pollution that contributes to coastal hypoxic zones.
      The performance and reliability of natural and engineered systems dependent upon
      microbially mediated processes, such as the denitrifying biofilters, can be
      affected by the spatial structure of their microbial communities. Furthermore,
      our understanding of the relationship between microbial community composition and
      function is influenced by the spatial distribution of samples.In this study we
      characterized the spatial structure of bacterial communities in a denitrifying
      biofilter in central Illinois. Bacterial communities were assessed using
      automated ribosomal intergenic spacer analysis for bacteria and terminal
      restriction fragment length polymorphism of nosZ for denitrifying bacteria.Non
      metric multidimensional scaling and analysis of similarity (ANOSIM) analyses
      indicated that bacteria showed statistically significant spatial structure by
      depth and transect,while denitrifying bacteria did not exhibit significant
      spatial structure. For determination of spatial patterns, we developed a package
      of automated functions for the R statistical environment that allows directional
      analysis of microbial community composition data using either ANOSIM or Mantel
      statistics.Applying this package to the biofilter data, the flow path correlation
      range for the bacterial community was 6.4 m at the shallower, periodically in
      undated depth and 10.7 m at the deeper, continually submerged depth. These
      spatial structures suggest a strong influence of hydrology on the microbial
      community composition in these denitrifying biofilters. Understanding such
      spatial structure can also guide optimal sample collection strategies for
      microbial community analyses.

PMID- 24077654
TI  - A review on five cases of intramedullary dermoid cyst.
AB  - PURPOSE: Intramedullary dermoid cyst is a type of rare congenital intraspinal
      lesions. Its proximity and its strong adherence to the surrounding spinal cord
      tissue often make a complete resection of the cyst wall problematic. We
      retrospectively studied five cases of intramedullary dermoid cyst, focusing the
      recurrence of intramedullary dermoid cyst after surgery and the probable method
      to prevent the recurrence. METHODS: Five cases of intramedullary dermoid cyst
      with or without other concomitant deformities were retrospectively reviewed.
      Subjects consisted of three males and two females, aged 2-24 years. Diagnosis was
      confirmed by spinal MRI and pathology studies. Surgical outcomes were analyzed.
      In case 2, an Ommaya reservoir was implanted in the cystic cavity, and the cystic
      content was sucked though the Ommaya reservoir. An 18-113 months of follow-up was
      conducted. RESULTS: The contents of intramedullary dermoid cyst were loose and
      easy to be cleared in the operations. The cyst wall was closely adhered to the
      spinal cord, and complete resection was difficult. During the follow-up of 18-113
      months, the lesion reoccurred in three cases. CONCLUSION: Intramedullary dermoid
      cyst is prone to recurrence. The presence of residual cyst wall might be the
      cause of dermoid cyst recurrence. When a complete resection of cyst wall becomes
      infeasible, placement of an intraspinal Ommaya reservoir may help to delay and
      minimize clinical symptoms by aspiration of cystic contents in case of
      recurrence.

PMID- 24077653
TI  - Epigenetics of diabetic complications.
AB  - Type 1 and Type 2 diabetes are complex diseases associated with multiple
      complications, and both genetic and environmental factors have been implicated in
      these pathologies. While numerous studies have provided a wealth of knowledge
      regarding the genetics of diabetes, the mechanistic pathways leading to diabetes
      and its complications remain only partly understood. Studying the role of
      epigenetics in diabetic complications can provide valuable new insights to
      clarify the interplay between genes and the environment. DNA methylation and
      histone modifications in nuclear chromatin can generate epigenetic information as
      another layer of gene transcriptional regulation sensitive to environmental
      signals. Recent evidence shows that key biochemical pathways and epigenetic
      chromatin histone methylation patterns are altered in target cells under diabetic
      conditions and might also be involved in the metabolic memory phenomenon noted in
      clinical trials and animal studies. New therapeutic targets and treatment options
      could be uncovered from an in-depth study of the epigenetic mechanisms that might
      perpetuate diabetic complications despite glycemic control.

PMID- 24077655
TI  - Genomic sequence analysis of Helicoverpa armigera nucleopolyhedrovirus isolated
      from Australia.
AB  - The complete genomic sequence of Helicoverpa armigera nucleopolyhedrovirus from
      Australia, HearNPV-Au, was determined and analyzed. The HearNPV-Au genome was
      130,992 bp in size with a G+C content of 39 mol% and contained 134 predicted open
      reading frames (ORFs) consisting of more than 150 nucleotides. HearNPV-Au shared
      94 ORFs with AcMNPV, HearSNPV-G4 and SeMNPV, and was most closely related to
      HearSNPV-G4. The nucleotide sequence identity between HearNPV-Au and HearSNPV-G4
      genome was 99%. The major differences were found in homologous regions (hrs) and
      baculovirus repeat ORFs (bro) genes. Five hrs and two bro genes were identified
      in the HearNPV-Au genome. All of the 134 ORFs identified in HearNPV-Au were also
      found in HearSNPV-G4, except the homologue of ORF59 (bro) in HearSNPV-G4. The
      sequence data strongly suggested that HearNPV-Au and HearSNPV-G4 belong to the
      same virus species.

PMID- 24077656
TI  - Viroid-like RNAs from cherry trees affected by leaf scorch disease: further data
      supporting their association with mycoviral double-stranded RNAs.
AB  - Cherry trees from Spain affected by cherry leaf scorch (CLS), a fungal disease
      proposed to be caused by Apiognomonia erythrostoma, show symptoms (translucent
      chlorotic leaf spots evolving into rusty areas) very similar to those of cherry
      chlorotic rusty spot disease (CCRS) and Amasya cherry disease, reported in Italy
      and Turkey, respectively. The three maladies are closely associated with 10-12
      double-stranded viral RNAs, and CCRS is additionally associated with two cherry
      small circular RNAs (cscRNA1 and cscRNA2). Here, we report that a small viroid
      like RNA similar to the CCRS-associated cscRNA1 is also present in CLS-affected
      trees, thus extending the link between the two diseases. Both CLS and CCRS
      cscRNA1 elements have common features, including sequence identity (88%), a
      predicted quasi rod-like conformation with short bifurcations at both termini,
      and the presence of hammerhead ribozymes in the strands of both polarities.
      However, cscRNA2, apparently derived from cscRNA1 by deletion of a short hairpin,
      was not detected in CLS-affected material. Although the biological nature of
      cscRNAs is unknown, the identification of at least cscRNA1 in different cherry
      cultivars and in two distinct geographic areas (Spain and Italy), always in close
      association with the same mycoviral dsRNAs, supports that these viroid-like RNAs
      could be satellite RNAs.

PMID- 24077658
TI  - Learning Incoherent Sparse and Low-Rank Patterns from Multiple Tasks.
AB  - We consider the problem of learning incoherent sparse and low-rank patterns from
      multiple tasks. Our approach is based on a linear multi-task learning
      formulation, in which the sparse and low-rank patterns are induced by a
      cardinality regularization term and a low-rank constraint, respectively. This
      formulation is non-convex; we convert it into its convex surrogate, which can be
      routinely solved via semidefinite programming for small-size problems. We propose
      to employ the general projected gradient scheme to efficiently solve such a
      convex surrogate; however, in the optimization formulation, the objective
      function is non-differentiable and the feasible domain is non-trivial. We present
      the procedures for computing the projected gradient and ensuring the global
      convergence of the projected gradient scheme. The computation of projected
      gradient involves a constrained optimization problem; we show that the optimal
      solution to such a problem can be obtained via solving an unconstrained
      optimization subproblem and an Euclidean projection subproblem. We also present
      two projected gradient algorithms and analyze their rates of convergence in
      details. In addition, we illustrate the use of the presented projected gradient
      algorithms for the proposed multi-task learning formulation using the least
      squares loss. Experimental results on a collection of real-world data sets
      demonstrate the effectiveness of the proposed multi-task learning formulation and
      the efficiency of the proposed projected gradient algorithms.

PMID- 24077657
TI  - Do comorbid anxiety disorders moderate the effects of psychotherapy for bipolar
      disorder? Results from STEP-BD.
AB  - OBJECTIVE: At least 50% of individuals with bipolar disorder have a lifetime
      anxiety disorder. Individuals with both bipolar disorder and a co-occurring
      anxiety disorder experience longer illness duration, greater illness severity,
      and poorer treatment response. The study explored whether comorbid lifetime
      anxiety in bipolar patients moderates psychotherapy treatment outcome. METHOD: In
      the Systematic Treatment Enhancement Program randomized controlled trial of
      psychotherapy for bipolar depression, participants received up to 30 sessions of
      intensive psychotherapy (family-focused therapy, interpersonal and social rhythm
      therapy, or cognitive-behavioral therapy) or collaborative care, a three-session
      comparison treatment, plus pharmacotherapy. Using the number needed to treat, we
      computed effect sizes to analyze the relationship between lifetime anxiety
      disorders and rates of recovery across treatment groups after 1 year. RESULTS: A
      total of 269 patients (113 women) with a comorbid lifetime anxiety disorder
      (N=177) or without a comorbid lifetime anxiety disorder (N=92) were included in
      the analysis. Participants with a lifetime anxiety disorder were more likely to
      recover with psychotherapy than with collaborative care (66% compared with 49%
      recovered over 1 year; number needed to treat=5.88, small to medium effect). For
      patients without a lifetime anxiety disorder, there was no difference between
      rates of recovery in psychotherapy compared with collaborative care (64% compared
      with 62% recovered; number needed to treat=50, small effect). Participants with
      one lifetime anxiety disorder were likely to benefit from intensive psychotherapy
      compared with collaborative care (84% compared with 53% recovered; number needed
      to treat=3.22, medium to large effect), whereas patients with multiple anxiety
      disorders exhibited no difference in response to the two treatments (54% compared
      with 46% recovered; number needed to treat=12.5, small effect). CONCLUSIONS:
      Depressed patients with bipolar disorder and comorbid anxiety may be in
      particular need of additional psychotherapy for treating acute depression. These
      results need to be replicated in studies that stratify bipolar patients to
      treatments based on their anxiety comorbidity status.

PMID- 24077659
TI  - Younger and older adults' beliefs about the experience and expression of emotions
      across the life span.
AB  - OBJECTIVES: Although theorists acknowledge that beliefs about emotions may play a
      role in age-related emotion behavior, no research has explored these beliefs.
      This research examined beliefs about the experience and expression of emotions
      across the life span, especially across the adult years. METHODS: Younger and
      older adults rated the extent to which infants, children, adolescents, young
      adults, middle-aged adults, and older adults were likely to experience and
      express a range of emotions. RESULTS: Younger and older adults held similar
      beliefs about the course of emotions across the life span. Moreover, these
      beliefs differed across emotion categories. In particular, although older adults
      were believed to experience and express fewer highly charged, negative emotions,
      they were expected to be more likely to experience and express positive, low
      arousal emotions, as well as negative, low arousal emotions. The experience and
      expression of positive, high arousal emotions were seen as more characteristic of
      very young age groups as opposed to older age groups. DISCUSSION: These findings
      beg questions about if and how beliefs about emotion may affect age-related
      emotion regulation strategies and other everyday emotion-focused behaviors, as
      well as social reactions to older adults observed experiencing and expressing
      particular types of emotions.

PMID- 24077660
TI  - Patterns of widowhood mortality.
AB  - OBJECTIVES: Becoming widowed is a known risk factor for mortality. This article
      examines the magnitude of, explanations for, and variation in the association
      between widowhood and mortality. Previous research on widowhood mortality has
      revealed variation by socioeconomic status (SES), in that SES is not protective
      in widowhood, and by gender, such that men's mortality increases more than
      women's mortality after the death of spouse. METHOD: Using data from the Health
      and Retirement Study, we estimated Cox proportional hazard models to estimate the
      association between widowhood and mortality. RESULTS: Becoming widowed is
      associated with a 48% increase in risk of mortality. Approximately one third of
      the increase can be attributed to selection, in that those who become widows are
      socioeconomically disadvantaged. In contrast to previous studies, SES is
      protective for widows. Widowhood mortality risk increases for men if their wives'
      deaths were unexpected rather than expected; for women, the extent to which their
      husbands' death was expected matters less. DISCUSSION: Widowhood's harmful
      association with mortality show how strongly social support and individual's
      health and mortality are related. These findings support the larger literature on
      the importance of social support for health and longevity.

PMID- 24077661
TI  - The MDM2-p53 pathway: multiple roles in kidney development.
AB  - The molecular basis of nephron progenitor cell renewal and differentiation into
      nascent epithelial nephrons is an area of intense investigation. Defects in these
      early stages of nephrogenesis lead to renal hypoplasia, and eventually
      hypertension and chronic kidney disease. Terminal nephron differentiation, the
      process by which renal epithelial precursor cells exit the cell cycle and acquire
      physiological functions is equally important. Failure of terminal epithelial cell
      differentiation results in renal dysplasia and cystogenesis. Thus, a better
      understanding of the transcriptional frameworks that regulate early and late
      renal cell differentiation is of great clinical significance. In this review, we
      will discuss evidence implicating the MDM2-p53 pathway in cell fate determination
      during development. The emerging central theme from loss- and gain-of-function
      studies is that tight regulation of p53 levels and transcriptional activity is
      absolutely required for nephrogenesis. We will also discuss how post
      translational modifications of p53 (e.g., acetylation and phosphorylation) alter
      the spatiotemporal and functional properties of p53 and thus cell fate during
      kidney development. Mutations and polymorphisms in the MDM2-p53 pathway are
      present in more than 50 % of cancers in humans. This raises the question of
      whether sequence variants in the MDM2-p53 pathway increase the susceptibility to
      renal dysgenesis, hypertension or chronic kidney disease. With the advent of
      whole exome sequencing and other high throughput technologies, this hypothesis is
      testable in cohorts of children with renal dysgenesis.

PMID- 24077662
TI  - Evaluation of magnetic resonance imaging issues for implantable microfabricated
      magnetic actuators.
AB  - The mechanical robustness of microfabricated torsional magnetic actuators in
      withstanding the strong static fields (7 T) and time-varying field gradients (17
      T/m) produced by an MR system was studied in this investigation. The static and
      dynamic mechanical characteristics of 30 devices were quantitatively measured
      before and after exposure to both strong uniform and non-uniform magnetic fields.
      The results showed no statistically significant change in both the static and
      dynamic mechanical performance, which mitigate concerns about the mechanical
      stability of these devices in association with MR systems under the conditions
      used for this assessment. The MR-induced heating was also measured in a 3-T/128
      MHz MR system. The results showed a minimal increase (1.6  degrees C) in
      temperature due to the presence of the magnetic microactuator array. Finally, the
      size of the MR-image artifacts created by the magnetic microdevices were
      quantified. The signal loss caused by the devices was approximately four times
      greater than the size of the device.

PMID- 24077663
TI  - Sequential gemcitabine and platinum versus first-line combination  of gemcitabine
      and platinum for advanced pancreatic cancer  treatment: a retrospective study.
AB  - OBJECTIVE: The purpose of this study was to investigate the impact of
      combinational versus sequential gemcitabine and platinum on prognosis of advanced
      pancreatic cancer. METHODS: Two hundred and three patients with advanced
      pancreatic cancer were selected. They were divided into GemP (first-line
      gemcitabine and platinum), Gem-then-P(sequential gemcitabine and platinum),
      Gem/other (first-line gemcitabine-based therapy without subsequent platinum),and
      Gem (first-line gemcitabine-based therapy without subsequent systemic therapy)
      groups. The Kaplan-Meier method and log-rank test were used for survival
      analyses. Cox regression model and propensity score matching were used for
      prognostic analyses. RESULTS: The median survival was 12.5 months [95 %confidence
      interval (CI), 11.2-13.7] in the GemP group(N = 65), 8.3 months (95 % CI 5.0
      11.7) in the Gem-then-P group (N = 35), 11.6 months (95 % CI 4.6-18.5) in the
      Gem/other group (N = 26), and 4.7 months (95 % C I3.3-6.0) in the Gem group (N =
      77) (P<0.001). Considering the GemP and Gem-then-P groups, performance status,
      serum creatinine, and response to first-line treatment were independent
      prognostic factors for overall survival in the multivariate analysis. No specific
      factors were identified for predicting the choice between GemP and Gem-then-P.
      CONCLUSIONS: First-line gemcitabine and platinum-based combinations were not
      superior to sequential gemcitabine and platinum for overall survival. The best
      sequence of chemotherapy for advanced pancreatic cancer should be explored in
      future clinical trials.

PMID- 24077664
TI  - Concentration effects of sumatriptan on the properties of model membranes by
      molecular dynamics simulations.
AB  - In this work, we report a molecular dynamics simulations study of protonated
      sumatriptan (pSMT) in a fully hydrated bilayer of 1-palmitoyl-2-oleoyl-sn-glycero
      3-phosphatidyl-choline at the fluid lamellar phase. The simulations were carried
      out at three different drug/lipid stoichiometries, 1:75, 1:10 and 1:3, under NPT
      conditions. Our results show partition of pSMT between the lipid head-water
      interphase and water phase. The main interactions that stabilized the systems
      were hydrogen bonds, salt bridges and cation-pi. Besides, pSMT molecules have no
      access to the hydrophobic region of the bilayer at the studied concentrations.
      From an atomistic point of view, this work could contribute to the discussion of
      drug-membrane interactions regarding the limitation of sumatriptan to cross the
      blood-brain barrier.

PMID- 24077666
TI  - Crude extract of Fusarium oxysporum induces apoptosis and structural alterations
      in the skin of healthy rats.
AB  - We evaluate the biological and physicochemical effects of a Fusarium oxysporum
      crude extract (CE) on the skin of healthy rats. The CE is topically applied and
      subsequently the skin is collected after 3, 6, 12, and 24 h. The samples are
      analyzed by Fourier transform infrared photoacoustic spectroscopy (FTIR-PAS) and
      histomorphometric analysis. Terminal dUTP nick end labeling (TUNEL assay) is
      performed to detect both the cells in apoptosis and proliferation. There is a
      thickening of the epidermis after 6, 12, and 24 h and dermis after 12 and 24 h of
      CE application. A reduction of the dermis thickness is observed at 3 and 6 h. The
      treated skin shows higher labeling intensity by TUNEL at 3 h, while a higher
      intensity by proliferating cell nuclear antigen occurs at 3 and 12 h. FTIR-PAS
      data support the histology observations showing an increase in the absorption
      peaks in the dermis after the application of the CE. F. oxysporum CE permeated
      through the epidermis and the dermis, reaching the subcutaneous tissue, inducing
      cell apoptosis, and causing physicochemical changes in the organic molecules
      located in the dermis. This is the first known study associating
      histopathological and physical chemistry changes on healthy skin after the
      application of F. oxysporum CE.

PMID- 24077665
TI  - Tissue-specific isoform switch and DNA hypomethylation of the pyruvate kinase PKM
      gene in human cancers.
AB  - The M2 isoform of pyruvate kinase (PKM2) plays an important role in aerobic
      glycolysis and is a mediator of the Warburg effect in tumors. It was previously
      thought that tumor cells switch expression of PKM from normal tissue-expressed
      PKM1 to tumor-specific PKM2 via an alternative splicing mechanism. This view was
      challenged by a recent report demonstrating that PKM2 is already the major PKM
      isoform expressed in many differentiated normal tissues. Here, through analyses
      on sixteen tumor types using the cancer genome atlas RNA-Seq and exon array
      datasets, we confirmed that isoform switch from PKM1 to PKM2 occurred in
      glioblastomas but not in other tumor types examined. Despite lacking of isoform
      switches, PKM2 expression was found to be increased in all cancer types examined,
      and correlated strongly to poor prognosis in head and neck cancers. We further
      demonstrated that elevated PKM2 expression correlated well with the
      hypomethylation status of intron 1 of the PKM gene in multiple cancer types,
      suggesting epigenetic regulation by DNA methylation as a major mechanism in
      controlling PKM transcription in tumors. Our study suggests that isoform switch
      of PKM1 to PKM2 in cancers is tissue-specific and targeting PKM2 activity in
      tumors remains a promising approach for clinical intervention of multiple cancer
      types. 

PMID- 24077668
TI  - Optimized sample treatment protocol by solid-phase peptide libraries to enrich
      for protein traces.
AB  - Combinatorial peptide ligand libraries have been extensively used for the
      enrichment of very low-abundance proteins, while concomitantly reducing the
      concentration of major species. A number of biological extracts have been
      reported with great success. Nevertheless, there are examples where the
      enrichment was not as good as expected. It has been demonstrated that the
      protocol itself may be responsible for the final results and is not necessarily
      applied as it should. In this paper, technical details along with important
      suggestions are given for an optimized enrichment of gene products present at
      trace levels among very many other proteins.

PMID- 24077667
TI  - Fecal calprotectin, MMP-9, and human beta-defensin-2 levels in pediatric
      inflammatory bowel disease.
AB  - PURPOSE: Fecal MMP-9 and human beta-defensin-2 (HBD-2)levels, potential markers
      of intestinal inflammation, are in sufficiently explored in pediatric
      inflammatory bowel disease(IBD). The aim was to study fecal MMP-9 and HBD-2 in
      pediatric IBD to compare their performance to calprotectin and to study whether
      they would provide additional value in categorizing patients according to their
      disease subtype. METHODS: Fecal calprotectin, MMP-9, and HBD-2 levels were
      measured with ELISA in 110 pediatric patients with IBD(Crohn's disease, n = 68;
      ulcerative colitis (UC), n = 27; unclassified, n = 15; median age, 14). To
      compare the performance of the fecal markers, the area under the receiver
      operating characteristics curve (+/-95 % CI) was used. In addition,the best cut
      off values of each measure to differentiate IBD patients and controls (n = 27
      presenting with diarrhea, abdominal pain, and/or anemia) were derived by
      maximizing sensitivity and specificity. RESULTS: Of the fecal markers studied,
      calprotectin performed best for separation of IBD and non-IBD patients with the
      are a under curve (AUC) of 0.944 (95 % CI, 0.907 to 0.981). For MMP-9, AUC was
      0.837 (95% CI, 0.766 to 0.909), the levels being significantly higher in active
      IBD and in UC compared with Crohn's disease (p = 0.0013), but categorization of
      these patient groups did not take place. HBD-2 did not categorize any of the
      studied groups. CONCLUSIONS: Calprotectin was the best fecal marker in pediatric
      IBD, but MMP-9 showed almost comparable performance in UC, suggesting
      applicability as a surrogate marker of inflammation. Fecal HBD-2 did not bring
      information to the disease characteristics of pediatric IBD patients.

PMID- 24077669
TI  - Multiple forms of mouse antizyme inhibitor 1 mRNA differentially regulated by
      polyamines.
AB  - Antizyme inhibitor 1 (Azin1), a positive regulator of cellular polyamines, is
      induced by various proliferative stimuli and repressed by polyamines. It has been
      reported that the translational repression of Azin1 by polyamines involves an
      upstream open reading frame on the mRNA, but little has been known about
      polyamine effect on its transcription or splicing. We found multiple forms of
      Azin1 transcripts formed by alternative splicing and initiation of transcription
      from putative alternative start sites. One of the novel splice variants, Azin1-X,
      has a premature termination codon on 5' extension of exon 7, encodes a C-terminal
      truncated form of protein (Azin1DeltaC), and is subject to nonsense-mediated mRNA
      decay. 2-Difluoromethylornithine (DFMO), an inhibitor of polyamine synthesis,
      increased both transcription from the canonical transcription start site and the
      ratio of the full-length mRNA to Azin1-X mRNA, whereas polyamines show the
      opposite effect. Thus, polyamines regulate two novel steps of Azin1 expression,
      namely the transcription and a particular splicing pattern, both of which may
      affect the level of mRNA encoding the full-length active Azin1 protein.

PMID- 24077670
TI  - Intercellular protein expression variability as a feature of stem cell
      pluripotency.
AB  - The expression of pluripotent stem cell protein markers, self-renewal, the
      potential to differentiate in cell types of all three germlines and teratoma
      formation in nude mice form the spectrum of the stringent pluripotency criteria
      for human stem cells. Currently, intercellular variability is discussed as an
      additional putative defining property of pluripotent stem cells. In future, it
      will be of relevance to clarify the genesis of intercellular variability for each
      stem cell line/population before its application in basic science or therapy.
      Furthermore, for a better understanding of stemness it will be indispensable to
      separately investigate the issue of intercellular variability for each feature of
      pluripotency.

PMID- 24077671
TI  - Anatomic ACL reconstruction produces greater graft length   change during knee
      range-of-motion than transtibial technique.
AB  - PURPOSE: Because distance between the knee ACL femoral and tibial footprint
      centrums changes during knee range-of-motion, surgeons must understand the effect
      of ACL socket position on graft length, in order to avoid graft rupture which may
      occur when tensioning and fixation is performed at the incorrect knee flexion
      angle. The purpose of this study is to evaluate change in intra-articular length
      of a reconstructed ACL during knee range-of-motion comparing anatomic versus
      transtibial techniques. METHODS: After power analysis, seven matched pair
      cadaveric knees were tested. The ACL was debrided, and femoral and tibial
      footprint centrums for anatomic versus transtibial techniques were identified and
      marked. Asuture anchor was placed at the femoral centrum and a custom, cannulated
      suture-centring device at the tibial centrum, and excursion of the suture,
      representing length change of an ACL graft during knee range-of-motion, was
      measured in millimeters and recorded using a digital transducer. RESULTS: Mean
      increase in length as the knee was ranged 120 degrees -0 degrees  (full
      extension) was 4.5 mm (+/-2.0 mm) for transtibial versus 6.7 mm (+/-0.9 mm) for
      anatomic ACL technique. A significant difference in length change occurs during
      knee range-of-motion both within groups and between the two groups. CONCLUSIONS:
      Change in length of the ACL intra-articular distance during knee range-of-motion
      is greater for anatomic socket position compared to transtibial position.
      Surgeons performing anatomic single-bundle ACL reconstruction may tension and fix
      grafts with the knee in full extension to minimize risk of graft stretch or
      rupture or knee capture during full extension. This technique may also result in
      knee anterior-posterior laxity in knee flexion.

PMID- 24077672
TI  - Clinical testing of otolith function: perceptual thresholds and myogenic
      potentials.
AB  - Cervical and ocular vestibular-evoked myogenic potential (cVEMP/oVEMP) tests are
      widely used clinical tests of otolith function. However, VEMP testing may not be
      the ideal measure of otolith function given the significant inter-individual
      variability in responses and given that the stimuli used to elicit VEMPs are not
      physiological. We therefore evaluated linear motion perceptual threshold testing
      compared with cVEMP and oVEMP testing as measures of saccular and utricular
      function, respectively. A multi-axis motion platform was used to measure
      horizontal (along the inter-aural and naso-occipital axes) and vertical motion
      perceptual thresholds. These findings were compared with the vibration-evoked
      oVEMP as a measure of utricular function and sound-evoked cVEMP as a measure of
      saccular function. We also considered how perceptual threshold and cVEMP/oVEMP
      testing are each associated with Dizziness Handicap Inventory (DHI) scores. We
      enrolled 33 patients with bilateral vestibulopathy of different severities and 42
      controls to have sufficient variability in otolith function. Subjects with
      abnormal oVEMP amplitudes had significantly higher (poorer) perceptual thresholds
      in the inter-aural and naso-occipital axes in age-adjusted analyses; no
      significant associations were observed for vertical perceptual thresholds and
      cVEMP amplitudes. Both oVEMP amplitudes and naso-occipital axis perceptual
      thresholds were significantly associated with DHI scores. These data suggest that
      horizontal perceptual thresholds and oVEMPs may estimate the same underlying
      physiological construct: utricular function.

PMID- 24077673
TI  - Anthropogenic edges, isolation and the flowering time and fruit set of
      Anadenanthera peregrina, a cerrado savanna tree.
AB  - Fragmentation exposes plants to extreme environmental conditions with
      implications for species phenology and reproduction.We investigated whether
      isolation and edge effects influence size, flowering time, fruit set, and
      seedling establishment of Anadenanthera peregrina var. falcata. We compared trees
      in the interior (n =85), and on the edge (n =74) of a cerrado savanna fragment as
      well as in a pasture (n =26) with respect to size, flowering phenology, flower
      and fruit production, fruit and seed set, predispersal seed predation, and
      seedling establishment. Trees in the pasture were larger and produced a higher
      number of flowers and fruits than trees on the edge and interior, yet seed set
      did not differ across environments. The plant size structure explained the flower
      and fruit production, and the self-compatibility breeding system caused a similar
      seed set regardless of the environment. First flowering was later and fruit set
      higher in the interior. We argue that time of first flower influenced the fruit
      set of Anadenathera. Edge and isolated trees started to flower earlier as a
      response to microclimatic conditions--mainly temperature--reducing the fruit set.
      Predispersal seed predation was lower among pasture trees. Conversely, we found
      seedlings only on the edge and in the interior of cerrado, suggesting that the
      pasture was of poor quality habitat for Anadenanthera recruitment. Isolation
      affected the plant size structure and reproduction of Anadenanthera trees.
      Studies comparing plant phenology under contrasting environmental conditions may
      offer clues on how global change may affect plant reproduction in the tropics.

PMID- 24077674
TI  - Evaluation of the plan for surveillance and controlling of the effects of heat
      waves in Madrid.
AB  - This paper presents evaluation of a plan for surveillance of and controlling the
      effects of heat-related mortality (PSCEHW), implemented in Madrid in 2004 through
      a time series analysis conducted with ARIMA modeling. From the public health
      point of view, prevention plans should be implemented as adaptive measures to
      heat waves. In 2003, the impact attributable to the heat wave was an increase in
      mortality per  degrees C of 22.39 %. All heat waves since 2003 have been of lower
      intensity, and yet, in 2005 there was a heat wave of lower intensity that had a
      greater impact, i.e. an increase in mortality per  degrees C of 45.71 %. With the
      methodology used here, we cannot say whether implementation of PSCEHW has
      resulted in a decrease of mortality attributable to high temperatures in the city
      of Madrid.

PMID- 24077676
TI  - Direct inguinal hernias and anterior surgical approach are risk factors for
      female inguinal hernia recurrences.
AB  - PURPOSE: The purpose of this study was to establish the risk of recurrence after
      direct and indirect inguinal hernia operation in a large-scale female population
      and to establish the relationship between the type of hernia at the primary and
      recurrent procedure. METHODS: Using data from the Danish Hernia Database (DHDB),
      a cohort was generated: all females operated on electively for a primary inguinal
      hernia by either Lichtenstein's technique or laparoscopy from 1998 to 2012.
      Within this prospectively collected cohort, the hernia type at the primary
      procedure (direct inguinal hernia (DIH), indirect inguinal hernia (IIH),
      combination hernia), the hernia type at the recurrent procedure (DIH, IIH,
      combination hernia, femoral hernia), anesthesia type, and time from primary
      procedure to reoperation were registered. RESULTS: A total of 5,893 females with
      primary elective inguinal hernia operation on in the study period (61 % IIH, 37 %
      DIH, 2 % combined hernias) were included with a median follow-up time of 72
      months (range 0 to 169). A total of 305 operations for suspected recurrences were
      registered (61 % inguinal recurrences, 38 % femoral recurrences, 1 % no hernias),
      which corresponded to an overall reoperation rate of 5.2 %. All femoral
      recurrences occurred after a previous open anterior operation. The crude
      reoperation rate after primary DIH operation was 11.0 %, 3.0 % after primary IIH
      operation and 0.007 % after combined hernia operation (p < 0.001). The
      multivariate adjusted analysis found that DIH at primary operation was a
      substantial risk factor for recurrence with a hazard ratio of 3.1 (CI 95 % 2.4
      3.9) compared with IIH at primary operation (p < 0.001), and that laparoscopic
      operation gave a lower risk of recurrence with a hazard ratio of 0.57 (CI 95 %
      0.43-0.75) compared with Lichtenstein's technique (p < 0.001). The risk of
      femoral recurrence was correlated to operation for DIH with a hazard ratio of 2.4
      (CI 95 % 1.7-3.5) compared with operation for IIH. CONCLUSION: In a female
      nationwide prospectively gathered cohort, we found that operation for a DIH
      resulted in a higher risk of reoperation than operation for an IIH. We found that
      femoral hernia recurrences exclusively existed after anterior open primary
      operation.

PMID- 24077675
TI  - Glucose conjugation for the specific targeting and treatment of cancer.
AB  - Cancers of diverse origins exhibit marked glucose avidity and high rates of
      aerobic glycolysis. Increased understanding of this dysfunctional metabolism
      known as the Warburg effect has led to an interest in targeting it for cancer
      therapy. One promising strategy for such targeting is glycoconjugation, the
      linking of a drug to glucose or another sugar. This review summarizes the most
      salient examples of glycoconjugates, in which known cytotoxins or targeted
      anticancer therapeutics have been linked to glucose (or another glucose
      transporter substrate sugar) for improved cancer targeting and selectivity.
      Building on these examples, this review also provides a series of guidelines for
      the design and mechanistic evaluation of future glycoconjugates.

PMID- 24077677
TI  - From Shattered Assumptions to Weakened Worldviews: Trauma Symptoms Signal Anxiety
      Buffer Disruption.
AB  - The fundamental assertion of worldview-based models of posttraumatic stress
      disorder is that trauma symptoms result when traumatic experiences cannot be
      readily assimilated into previously held worldviews. In two studies, we test the
      anxiety buffer disruption hypothesis, which states that trauma symptoms result
      from the disruption of normal death anxiety-buffering functions of worldview. In
      Study 1, participants with trauma symptoms greater than the cutoff for PTSD
      evinced greater death-thought accessibility than those with sub-clinical or
      negligible symptoms after a reminder of death. In Study 2, participants with
      clinically significant trauma symptoms showed no evidence of worldview defense
      though death-thoughts were accessible. These results support the anxiety buffer
      disruption hypothesis, and suggest an entirely new approach to experimental PTSD
      research.

PMID- 24077678
TI  - The biophysics of renal sympathetic denervation using radiofrequency energy.
AB  - Renal sympathetic denervation is currently performed in the treatment of
      resistant hypertension by interventionists who otherwise do not typically use
      radiofrequency (RF) energy ablation in their clinical practice. Adequate RF
      lesion formation is dependent upon good electrode-tissue contact, power delivery,
      electrode-tissue interface temperature, target-tissue impedance and the size of
      the catheter's active electrode. There is significant interplay between these
      variables and hence an appreciation of the biophysical determinants of RF lesion
      formation is required to provide effective and safe clinical care to our
      patients. In this review article, we summarize the biophysics of RF ablation and
      explain why and how complications of renal sympathetic denervation may occur and
      discuss methods to minimise them.

PMID- 24077679
TI  - Disease distribution and outcome in troponin-positive patients with or without
      revascularization in a chest pain unit: results of the German CPU-Registry.
AB  - OBJECTIVES: The aim of this analysis was to compare troponin-positive patients
      presenting to a chest pain unit (CPU) and undergoing coronary angiography with or
      without subsequent revascularization. Leading diagnosis, disease distribution,
      and short-term outcomes were evaluated. BACKGROUND: Chest pain units are
      increasingly implemented to promptly clarify acute chest pain of uncertain
      origin, including patients with suspected acute coronary syndrome (ACS). METHODS:
      A total of 11,753 patients were prospectively enrolled into the German CPU
      Registry of the German Cardiac Society between December 2008 and April 2011. All
      patients with elevated troponin undergoing a coronary angiography were selected.
      Three months after discharge a follow-up was performed. RESULTS: A total of 2,218
      patients were included. 1,613 troponin-positive patients (72.7 %) underwent a
      coronary angiography with subsequent PCI or CABG and had an ACS in 96.0 %. In
      contrast, 605 patients (27.3 %) underwent a coronary angiography without
      revascularization and had an ACS in 79.8 %. The most frequent non-coronary
      diagnoses in non-revascularized patients were acute arrhythmias (13.4 %),
      pericarditis/myocarditis (4.5 %), decompensated congestive heart failure (3.7 %),
      Takotsubo cardiomyopathy (2.7 %), hypertensive crisis (2.4 %), and pulmonary
      embolism (0.3 %). During the 3-month followup, patients without revascularization
      had a higher mortality (12.1 vs. 4.5 %, p<0.0001) representing the major
      contributor to the higher rate of MACCE (15.1 vs. 8.1 %, p<0.001). These data
      were confirmed in a subgroup analysis of ACS patients with or without
      revascularization. CONCLUSIONS: Patients presenting to a CPU with elevated
      troponin levels mostly suffer from ACS and in a smaller proportion a variety of
      different diseases are responsible. The short-term outcome in troponin-positive
      patients with or without an ACS not undergoing a revascularization was worse,
      indicating that these patients were more seriously ill than patients with
      revascularization of the culprit lesion. Therefore, an adequate diagnostic
      evaluation and improved treatment strategies are warranted.

PMID- 24077680
TI  - Socially assigned gender nonconformity: A brief measure for use in surveillance
      and investigation of health disparities.
AB  - Discrimination and violence targeting people perceived as gender nonconforming
      have been linked to a range of negative health outcomes, and large-scale
      representative data are needed to begin population surveillance of associated
      health disparities. A brief self-report measure of gender expression as perceived
      by others was tested using cognitive interviewing methods in a diverse sample of
      82 young adults aged 18-30 years, recruited from the New England region in the
      U.S. Results identified themes related to item clarity, gender expression
      variation, undesirability of highest or lowest ends of item range, and tension
      between self and others' perceptions. The item performed as expected and is
      recommended for use on studies of health disparities, including statewide and
      national public health surveillance tools.

PMID- 24077681
TI  - CCAT2, a novel long non-coding RNA in breast cancer: expression study and
      clinical correlations.
AB  - The clinical outcome of BC patients receiving the same treatment is known to vary
      considerably and thus, there is a compelling need to identify novel biomarkers
      that can select the patients that would benefit most from a given therapy and can
      predict the clinical outcome. The aim of this study was to determine the
      prognostic value of CCAT2, a novel long ncRNA recently characterized by our group
      and overlapping SNP rs6983267, in BC patients. We first evaluated by RT-qPCR and
      ISH the expression of CCAT2 in normal breast tissue and BC tissue and further
      analyzed CCAT2 expression in an independent set of 997 primary BC with regard to
      clinical, histological, pathological and other biological factors. Also, we
      explored the possibility of CCAT2 adding to the prognostic value of multivariate
      models that already included the traditional prognostic factors. Finally, we
      identified in in vitro models the impact of CCAT2 expression and SNP rs6983267
      genotype on cell migration and chemoresistance. Our results revealed that
      although overexpressed in BCs in two out of three sets of patients, and having
      the highest expression in lymph node negative (LNN) disease, CCAT2 expression
      levels are informative solely for a subgroup of BC patients, namely for patients
      with LNP disease that have received adjuvant CMF chemotherapy. For this subgroup
      high levels of CCAT2 suggest the patients will not benefit from CMF containing
      adjuvant chemotherapy (shorter MFS and OS). Additionally, we found that CCAT2
      upregulates cell migration and downregulates chemosensitivity to 5'FU in a
      rs6983267-independent manner. 

PMID- 24077683
TI  - Hydrolysis of milk-derived bioactive peptides by cell-associated extracellular
      peptidases of Streptococcus thermophilus.
AB  - The trend to confer new functional properties to fermented dairy products by
      supplementation with bioactive peptides is growing in order to encounter the
      challenge of health-promoting foods. But these functional ingredients have not to
      be hydrolysed by proteases of bacteria used in the manufacture of these products.
      One of the two yoghurt bacteria, Streptococcus thermophilus, has long been
      considered as weakly proteolytic since its only cell wall-associated subtilisin
      like protease, called PrtS, is not always present. Nevertheless, a recent study
      pointed out a possible peptidase activity in certain strains. In this present
      study, the stability of milk-derived bioactive peptides, e.g. the anxiolytic
      peptide, alphas1-CN-(f91-97), in the presence of two different S. thermophilus
      strains with PrtS+ or PrtS- phenotype was studied. Both strains appeared to be
      capable of hydrolysing the alphas1-CN-(f91-97) and other bioactive peptides by
      recurrent removal of N-terminal residues. The hydrolysis was neither due to
      intracellular peptidases nor to HtrA protease. Results obtained showed that the
      observed activity originates from the presence at the surface of both strains of
      an extracellular aminopeptidase activity. Moreover, a cell wall-associated X
      prolyl dipeptidyl peptidase activity was also highlighted when beta-casomorphin-7
      was used as substrate. All of these findings suggest that, in order to use
      fermented milks as vector of bioactive peptides, the stability of these bioactive
      peptides in this kind of products implies to carefully characterize the potential
      action of the surface proteolytic enzymes of S. thermophilus.

PMID- 24077682
TI  - Anti-septic effects of pellitorine in HMGB1-induced inflammatory responses in
      vitro and in vivo.
AB  - High mobility group box 1 (HMGB1) acts as a late mediator of vascular
      inflammatory conditions. Pellitorine (PT), an active amide compound from Asarum
      sieboldii, is known to possess antibacterial and anticancer properties. In this
      study, we investigated the anti-septic effects of PT against pro-inflammatory
      responses in human umbilical vein endothelial cells (HUVECs) induced by HMGB1 and
      the associated signaling pathways. According to our findings, treatment with PT
      resulted in inhibited release of HMGB1, down-regulation of HMGB1-dependent
      inflammatory responses in HUVECs, and inhibited HMGB1-mediated hyperpermeability
      and leukocyte migration in mice. In addition, treatment with PT resulted in
      reduced cecal ligation and puncture (CLP)-induced release of HMGB1 and sepsis
      related mortality. PT suppressed the production of tumor necrosis factor-alpha
      and interleukin 6 and the activation of nuclear factor-kappaB and extracellular
      regulated kinases 1/2 by HMGB1. Collectively, these results indicate the
      potential of PT as a candidate therapeutic agent for treatment of various severe
      vascular inflammatory diseases via inhibition of the HMGB1 signaling pathway. 

PMID- 24077684
TI  - Poly-gamma-glutamate from Bacillus subtilis inhibits tyrosinase activity and
      melanogenesis.
AB  - Poly-gamma-glutamate (gamma-PGA) has been considered as one of the most promising
      biomaterials with a wide range of applications, but there has been no report that
      directly shows the anti-tyrosinase and anti-melanogenesis properties of gamma
      PGA. In the present study, we investigated the inhibitory effects of gamma- PGA
      with low molecular weight (Mw; lgamma-PGA) and high Mw (hgamma-PGA) on mushroom
      tyrosinase and murine tyrosinase activities and on melanogenesis in B16 melanoma
      cells. First, we showed that both lgamma-PGA and hgamma-PGA could effectively
      inhibit mushroom tyrosinase activities including monophenolase and diphenolase
      activities in a dose-dependent manner. Second, both lgamma-PGA and hgamma-PGA
      showed strong anti-tyrosinase activity and anti-melanogenesis in B16 melanoma
      cells. Third, both lgamma-PGA and hgamma-PGA inhibited forskolin-induced
      tyrosinase activity and melanogenesis by decreasing the levels of intracellular
      reactive oxygen species and nitric oxide while increasing the catalase activity
      in B16 cells. This is the first report on the anti-melanogenesis effect of gamma
      PGA, which suggests that gamma-PGA could have a potential in the cosmetic skin
      whitening business, therapeutic applications and the food industry.

PMID- 24077685
TI  - Child and parent perspectives of the chronic graft-versus-host disease (cGVHD)
      symptom experience: a concept elicitation study.
AB  - PURPOSE: Chronic graft-versus-host disease (cGVHD) is a significant cause of
      mortality and morbidity after allogeneic hematopoietic cell transplant and is
      associated with a wide range of distressing symptoms. A pediatric measure of
      cGVHD-related symptoms is needed to advance clinical research. Our aim was to
      elicit descriptions of the cGVHD symptom experience directly from children and to
      compare the specific language used by children to describe their symptoms and the
      comprehension of symptom concepts across the developmental spectrum. METHODS: We
      used qualitative methods to identify the phrases, terms, and constructs that
      children (ages 5-8 [n =8], 9-12 [n =8], and 13-17 [n =8]) with cGVHD employ when
      describing their symptoms. The symptom experience of each participant was
      determined through individual interviews with each participant and parent (5-7
      year olds were interviewed together with a parent). Medical practitioners with
      experience in evaluating cGVHD performed clinical assessments of each
      participant. RESULTS: Pediatric transplant survivors and their parents identified
      a wide range of bothersome cGVHD symptoms, and common concepts and terminologies
      to describe these experiences emerged. Overall concordance between patient and
      parent reports was moderate (70-75 %). No consistent pattern of child under- or
      over-reporting in comparison to the parent report was observed. CONCLUSION: These
      study results identify concepts and vocabulary to inform item generation for a
      new pediatric self-report measure of cGVHD symptoms for use in clinical research.
      The findings also confirm the prevalence and nature of symptom distress in
      pediatric patients with cGVHD and support implementation of systematic approaches
      to symptom assessment and intervention in routine clinical practice.

PMID- 24077686
TI  - Timing of code status documentation and end-of-life outcomes in patients admitted
      to an oncology ward.
AB  - PURPOSE: Guidelines recommend documentation of care preferences for patients with
      advanced cancer upon hospital admission.We assessed end-of-life outcomes for
      patients who did or did not have code status (CS) documented within 48 h of
      admission. METHODS: This was a retrospective cohort study of patients who died on
      an inpatient oncology ward between January 2004 and February 2009. Primary end-of
      life outcomes were "code blues" and cardiopulmonary resuscitation (CPR) attempts;
      secondary outcomes included unsuccessful CPR attempts, intensive care unit (ICU),
      consultations, and ICU admissions. Using logistic regression, outcomes were
      compared between those with and without CS documentation <= 48 h from admission
      (full code or do-not-resuscitate), controlling for significant confounders.
      RESULTS: The 336 patients had a median age of 61 years; 97 % had advanced cancer.
      The median time from admission to death was 12 days (range <1-197 days); 151
      patients (45 %) had CS documentation <= 48 h from admission. Controlling for
      confounders of reason for admission and marital status, patients with CS
      documentation <= 48 h from admission had fewer "code blues" (2 vs. 15 %; adjusted
      odds ratio(AOR) 0.12, 95% confidence interval (CI) 0.02-0.43), CPR attempts (1
      vs. 11 %; AOR 0.12, 95 % CI 0.01-0.51), unsuccessful CPR attempts (0 vs. 11 %),
      ICU consultations (9 vs. 30 %; AOR 0.19, 95 % CI 0.08-0.40) and ICU admissions (2
      vs. 5 %; AOR 0.18, 95 %CI 0.02-0.85). CONCLUSIONS: In patients who died on an
      oncology ward, CS documentation within 48 h of admission was associated with less
      aggressive end-of-life care, regardless of the reason for admission.

PMID- 24077687
TI  - Rigid intramedullary nail fixation of femoral fractures in adolescents: what
      evidence is available?
AB  - BACKGROUND: Femoral fracture in adolescents is a significant injury. It is
      generally agreed that operative fixation is the treatment of choice, and rigid
      intramedullary nail fixation is a treatment option. However, numerous types of
      rigid nails to fix adolescent femoral fractures have been described. Hence, the
      aim of this paper was to collate and evaluate the available evidence for managing
      diaphyseal femoral fractures in adolescents using rigid intramedullary nails.
      MATERIALS AND METHODS: A literature search was undertaken using the healthcare
      database website ( http://www.library.nhs.uk/hdas ). Medline, CINAHL, Embase, and
      the Cochrane Library databases were searched to identify prospective and
      retrospective studies of rigid intramedullary nail fixation in the adolescent
      population. RESULTS: The literature search returned 1,849 articles, among which
      51 relevant articles were identified. Of these 51 articles, 23 duplicates were
      excluded, so a total of 28 articles were reviewed. First-generation nails had a
      high incidence of limb length discrepancy (Kuntscher 5.8 %, Grosse-Kempf 9 %),
      whilst second-generation nails had a lower incidence (Russell-Taylor 1.7 %, AO
      2.6 %). Avascular necrosis was noted with solid Ti nails (2.6 %), AO femoral
      nails (1.3 %) and Russell-Taylor nails (0.85 %). These complications have not
      been reported with the current generation of nails. CONCLUSIONS: Rigid
      intramedullary nail fixation of femoral fractures in adolescents is a useful
      procedure with good clinical results. A multiplanar design and lateral
      trochanteric entry are key to a successful outcome of titanium alloy nail
      fixation.

PMID- 24077688
TI  - DNA binding, antitumor activities, and hydroxyl radical scavenging properties of
      novel oxovanadium (IV) complexes with substituted isoniazid.
AB  - Four novel oxovanadium(IV) complexes-[VO(PAHN)(phen)] (1; PAHN is 4
      pyridinecarboxylic acid, 2-[(2-hydroxy)-1-naphthalenylene] hydrazide, phen is
      1,10-phenanthroline), [VO(PAHN)(bpy)] (2; bpy is 2,2'-bipyridine),
      [VO(PAH)(phen)] (3; PAH is 4-pyridinecarboxylic acid, 2-[(2-hydroxy)-1
      phenyl]methylene hydrazide), and [VO(PAH)(bpy)] (4)-have been synthesized and
      characterized by elemental analysis, UV-vis spectroscopy, electrospray ionization
      mass spectrometry, IR spectroscopy, 1H-NMR spectroscopy, and 13C-NMR
      spectroscopy. Their interactions with calf thymus DNA were investigated. The
      results suggest that these complexes bind to DNA in an intercalative mode. All
      four complexes exhibited highly cytotoxic activity against tumor cells (SH-SY5Y,
      MCF-7, and SK-N-SH), with 50 % inhibitory concentrations of the same order of
      magnitude as for cisplatin or of lower order of magnitude. Complex 1 exhibited
      the highest interaction ability and was found to be the most potent antitumor
      agent among the four complexes. It can cause G2/M phase arrest of the cell cycle,
      induces significant apoptosis in SK-N-SH cells, and displays typical
      morphological apoptotic characteristics. In addition, their hydroxyl radical
      scavenging properties have been tested, and complex 1 was the best inhibitor.

PMID- 24077689
TI  - A comprehensive five-phase rehabilitation programme after hip arthroscopy for
      femoroacetabular impingement.
AB  - PURPOSE: Recent advancements in the understanding of hip biomechanics have led to
      the development of techniques to remove bony impingement and repair and/or
      preserve the labrum during hip arthroscopy. Although much attention in the
      literature is devoted to diagnosis and treatment, there is little information
      about post-operative rehabilitation. Therefore, the purpose of this review is to
      (1) provide a five-phase rehabilitation protocol following arthroscopic treatment
      for FAI and (2) report clinical and functional outcomes of patients following
      this protocol at minimum 1-year follow-up, in order to provide the surgeon and
      therapist with a protocol that is supported by clinical data. METHODS: All
      consecutive patients undergoing hip arthroscopy and subsequent five-phase
      rehabilitation protocol at a single institution from 1 April 2011 to 1 April 2012
      were analysed. Inclusion criteria were as follows: no prior ipsilateral hip
      surgery, completion of the five-phase rehabilitation protocol, minimum 1-year
      follow-up, and documented outcome scores. Prospective outcomes were assessed with
      modified Harris hip score (MHHS) and hip outcome score (HOS). RESULTS: Fifty-two
      patients (19 male and 33 female) met the inclusion criteria with a median age of
      42 (range 16-59) years. Mean MHHS, HOS-ADL, and HOS-sport scores at a mean 12.5
      (range 12-15) months were 80.1 +/- 19.9 (0-100), 83.6 +/- 19.2 (13.2-100), and
      70.3 +/- 27.0 (0-100), respectively. CONCLUSION: This five-phase rehabilitation
      programme provides a framework where progression from surgery to increasing post
      operative activity level can take place in a predictable manner. Patients
      following this rehabilitation protocol after hip arthroscopy demonstrated
      satisfactory clinical and functional outcomes, validating its implementation.

PMID- 24077692
TI  - Engineering at the limits of antibody space.

PMID- 24077690
TI  - Post-operative blood loss in total knee arthroplasty: knee flexion versus
      pharmacological techniques.
AB  - PURPOSE: To compare the blood loss and the blood transfusion between a control
      group and a group of patients following either a local administration of
      tranexamic acid or a mechanical post-operative knee flexion, a controlled
      randomized study was performed. METHODS: Sixty patients affected by primary knee
      osteoarthritis and candidates to receive a primary unilateral total knee
      arthroplasty were enrolled in a prospective, randomized, controlled study.
      Exclusion criteria were the following: tranexamic acid allergy, the use of
      pharmacological anticoagulant therapy, previous knee surgery and renal failure.
      For each patient, the following parameters were investigated: the blood loss
      volume, the haemoglobin and haematocrit concentrations and the blood transfusion
      needs. RESULTS: Compared to the control group, the administration of systemic
      tranexamic acid significantly reduces (p < 0.05) both the blood loss (average
      reduction 39.8%) and the blood transfusion needs (64%). Furthermore, the
      tranexamic acid group shows a significant reduction (p < 0.05) compared to the
      knee flexion group of the blood loss (average reduction 31.8%) and the
      transfusion needs (65%). However, even if the knee flexion technique slightly
      reduces the blood loss (average reduction 11.6%) compared to the control group,
      this difference is not statistically significant (n.s.). Moreover, this treatment
      did not reduce the transfusion needs compared to the control group (n.s.).
      Incidence of complications was not influenced by any of the treatments.
      CONCLUSIONS: The use of tranexamic acid compared to knee flexion and to control
      group significantly reduces blood loss and transfusion needs, without wound
      complications or symptomatic deep vein thrombosis. LEVEL OF EVIDENCE: Prospective
      therapeutic study, Level I.

PMID- 24077693
TI  - Plantago maxima leaves extract inhibits adipogenic action  of a high-fat diet in
      female Wistar rats.
AB  - PURPOSE: The primary objective of this study is to investigate the content of
      biologically active compounds producing an antioxidant effect in Plantago maxima
      and their influence on main mechanisms of dietary obesity development. METHODS:
      Biologically active compounds in P. maxima were tested using paper
      chromatography. In in vivo experiment, high-fat-fed Wistar rats obtained P.
      maxima water extract for 3 months. Morphometric parameters, weight gain, serum
      adipokines, and cytokines, as well as oxidative stress biomarkers in rats'
      tissues were evaluated. Gut microflora was also examined. RESULTS: Plantago
      maxima leaves used in the experiment contained significant amount of flavonoids,
      iridoids, phenol carboxylic acids, and tannins and ascorbic acid. Our in vivo
      experiment data demonstrate that P. maxima water extract prevents excessive
      adiposity in a diet-induced model. P. maxima consumption reduced serum leptin
      (twofold), macrophage chemoattractant protein-1 (sevenfold), tumornecrosis factor
      alpha (25%), and interleukine-6 (26%) levels. P. maxima water extract decreased
      adipose tissue oxidative stress biomarkers in rats fed a high-fat diet. In
      addition, increased bacterial growth in the diet-induced obesity model was
      reversed by the P. maxima extract treatment. CONCLUSION: Plantago maxima water
      extract possessed antiadipogenic, antidiabetic, antiinflammatory, antioxidant
      activity, and normalized gut microflora in a rat model of diet-induced excessive
      adiposity due to a high content of biologically active compounds.

PMID- 24077694
TI  - Phase-II metabolism limits the antiproliferative activity of urolithins in human
      colon cancer cells.
AB  - PURPOSE: Urolithins, gut microbiota metabolites derived from ellagic acid and
      ellagitannins, reach micromolar concentrations in the colon lumen where can have
      anti-inflammatory and anticancer effects. The antiproliferative activity of
      urolithins (Uro-A, Uro-B, Uro-C and Uro-D) and their most relevant in vivo
      glucuronides were evaluated in three human colon cancer cell lines (Caco-2, SW480
      and HT-29). METHODS: Cell proliferation was evaluated by 3-(4,5-dimethyl-2
      thiazolyl)-2,5-diphenyl-2H-tetrazolium bromide and Trypan blue exclusion assays.
      Cell cycle was evaluated by flow cytometry and urolithins metabolism by HPLC
      MS/MS. RESULTS: Urolithins inhibited cell proliferation and cell cycle
      progression in a time- and dose-dependent manner and arrested the cells at S and
      G2/M phases, depending on the urolithin. Uro-A exerted the highest
      antiproliferative activity, followed by Uro-C, Uro-D and Uro-B. Unlike Caco-2 and
      SW480 cells, HT-29 cells partially overcame the effects after 48 h, which was
      related to the complete glucuronidation of urolithins. Uro-A or Uro-B
      glucuronides did not affect cell cycle and showed lower antiproliferative
      activity than their aglycone counterparts. Uro-A or Uro-B plus inhibitors of drug
      efflux ABC transporters partially prevented the glucuronidation of urolithins in
      HT-29 cells which became more sensitive. CONCLUSIONS: Uro-A, Uro-B, Uro-C and Uro
      D exerted different antiproliferative effects depending on the colon cancer cell
      line. We also report here, for the first time, the role of ABC transporters and
      Phase-II metabolism in HT-29 cells as a mechanism of cancer resistance against
      urolithins due to their conversion to glucuronide conjugates that exerted lower
      antiproliferative activity.

PMID- 24077698
TI  - IkappaBalpha beyond the NF-kB dogma.

PMID- 24077695
TI  - Cl- channels in smooth muscle cells.
AB  - In smooth muscle cells (SMCs), the intracellular chloride ion (Cl-) concentration
      is high due to accumulation by Cl-/HCO3- exchange and Na+-K+-Cl-
      cotransportation. The equilibrium potential for Cl- (ECl) is more positive than
      physiological membrane potentials (Em), with Cl- efflux inducing membrane
      depolarization. Early studies used electrophysiology and nonspecific antagonists
      to study the physiological relevance of Cl- channels in SMCs. More recent reports
      have incorporated molecular biological approaches to identify and determine the
      functional significance of several different Cl- channels. Both "classic" and
      cGMP-dependent calcium (Ca2+)-activated (ClCa) channels and volume-sensitive Cl-
      channels are present, with TMEM16A/ANO1, bestrophins, and ClC-3, respectively,
      proposed as molecular candidates for these channels. The cystic fibrosis
      transmembrane conductance regulator (CFTR) has also been described in SMCs. This
      review will focus on discussing recent progress made in identifying each of these
      Cl- channels in SMCs, their physiological functions, and contribution to diseases
      that modify contraction, apoptosis, and cell proliferation.

PMID- 24077696
TI  - MaxiK channel and cell signalling.
AB  - The large-conductance Ca2+- and voltage-activated K+ (MaxiK, BK, BKCa, Slo1,
      KCa1.1) channel role in cell signalling is becoming apparent as we learn how the
      channel interacts with a multiplicity of proteins not only at the plasma membrane
      but also in intracellular organelles including the endoplasmic reticulum,
      nucleus, and mitochondria. In this review, we focus on the interactions of MaxiK
      channels with seven-transmembrane G protein-coupled receptors and discuss
      information suggesting that, the channel big C-terminus may act as the nucleus of
      signalling molecules including kinases relevant for cell death and survival.
      Increasing evidence indicates that the channel is able to associate with a
      variety of receptors including beta-adrenergic receptors, G protein-coupled
      estrogen receptors, acetylcholine receptors, thromboxane A2 receptors, and
      angiotensin II receptors, which highlights the varied functions that the channel
      has (or may have) not only in regulating contraction/relaxation of muscle cells
      or neurotransmission in the brain but also in cell metabolism, proliferation,
      migration, and gene expression. In line with this view, MaxiK channels have been
      implicated in obesity and in brain, prostate, and mammary cancers. A better
      understanding on the molecular mechanisms underlying or triggered by MaxiK
      channel abnormalities like overexpression in certain cancers may lead to new
      therapeutics to prevent devastating diseases.

PMID- 24077699
TI  - Should the dosage of controlled-release oxycodone in advanced cancer be modified
      on the basis of patient characteristics?
AB  - PURPOSE: This study aimed to investigate whether the characteristics of patients
      with advanced cancer explain the variability in oxycodone clearance, with the
      potential for this information to determine maintenance dosing. METHODS: Patients
      (n = 36) with advanced cancer who were receiving delayed-release oxycodone
      (Oxycontin(r)) (mean dose, 31.4 mg; range, 5-120 mg) mostly twice daily (mean
      duration = 80 days; range, 5-651 days) provided venous blood samples (n = 139,
      median = 3 per patient) drawn from 0.25 to 23.4 h post-dose. Plasma was assayed
      for oxycodone (mean = 39.4 ng/mL; range, 1-256 ng/mL) by high-performance liquid
      chromatography with tandem mass spectrometry detection. Pharmacokinetic modeling
      was performed using nonlinear mixed-effects modeling (NONMEM). RESULTS: A one
      compartment model with first-order absorption and elimination best described the
      data. Typical population values and between-subject variability (coefficient of
      variation, percent) for oxycodone clearance and the oral absorption rate constant
      were 73 L/h (31.9 %) and 0.0735 h (133 %), respectively. The volume of
      distribution was estimated based on literature values for intravenous oxycodone
      in cancer patients. The inclusion of weight, sex, age, creatinine clearance, and
      serum albumin concentration did not significantly explain pharmacokinetic
      variability in clearance or absorption rate constant. The subject with the most
      elevated liver function test values also had the lowest clearance per kilogram.
      CONCLUSIONS: Oxycodone clearance was similar to that reported previously for
      healthy adults. Despite reports that patient characteristics significantly affect
      oxycodone pharmacokinetics, our results do not support alteration of current
      prescribing practices for maintenance dosing of Oxycontin(r) in most patients
      with advanced cancer. The influence of marked liver dysfunction on oxycodone
      clearance requires further investigation.

PMID- 24077701
TI  - High-efficiency thermal asymmetric interlaced PCR (hiTAIL-PCR) for determination
      of a highly degenerated prophage WO genome in a Wolbachia strain infecting a fig
      wasp species.
AB  - Temperate bacteriophage WO is a model system for studying tripartite interactions
      among viruses, bacteria, and eukaryotes, especially investigations of the genomic
      stability of obligate intracellular bacteria. Few WO genomes exist because of the
      difficulty in isolating viral DNA from eukaryotic hosts, and most reports are by
      products of Wolbachia sequencing. Only one partial genome of a WO phage has been
      determined directly from isolated particles. We determine the complete genome
      sequence of prophage WO (WOSol) in Wolbachia strain wSol, which infects the fig
      wasp Ceratosolen solmsi (Hymenoptera: Chalcidoidea), by high-efficiency thermal
      asymmetric interlaced PCR. The genome of WOSol is highly degenerated and
      disrupted by a large region (14,267 bp) from Wolbachia. Consistent with previous
      molecular studies of multiple WO genomes, the genome of WOSol appears to have
      evolved by single nucleotide mutations and recombinations. 

PMID- 24077700
TI  - Depth-related changes in community structure of culturable mineral weathering
      bacteria and in weathering patterns caused by them along two contrasting soil
      profiles.
AB  - Bacteria play important roles in mineral weathering and soil formation. However,
      few reports of mineral weathering bacteria inhabiting subsurfaces of soil
      profiles have been published, raising the question of whether the subsurface
      weathering bacteria are fundamentally distinct from those in surface communities.
      To address this question, we isolated and characterized mineral weathering
      bacteria from two contrasting soil profiles with respect to their role in the
      weathering pattern evolution, their place in the community structure, and their
      depth-related changes in these two soil profiles. The effectiveness and pattern
      of bacterial mineral weathering were different in the two profiles and among the
      horizons within the respective profiles. The abundance of highly effective
      mineral weathering bacteria in the Changshu profile was significantly greater in
      the deepest horizon than in the upper horizons, whereas in the Yanting profile it
      was significantly greater in the upper horizons than in the deeper horizons. Most
      of the mineral weathering bacteria from the upper horizons of the Changshu
      profile and from the deeper horizons of the Yanting profile significantly
      acidified the culture media in the mineral weathering process. The proportion of
      siderophore-producing bacteria in the Changshu profile was similar in all
      horizons except in the Bg2 horizon, whereas the proportion of siderophore
      producing bacteria in the Yanting profile was higher in the upper horizons than
      in the deeper horizons. Both profiles existed in different highly depth-specific
      culturable mineral weathering community structures. The depth-related changes in
      culturable weathering communities were primarily attributable to minor bacterial
      groups rather than to a change in the major population structure. 

PMID- 24077703
TI  - Effect of bacteriophage application on Campylobacter jejuni loads in commercial
      broiler flocks.
AB  - Campylobacteriosis is the most frequent food-borne human enteritis. The major
      source for infection with Campylobacter spp. is broiler meat. Risk assessments
      consider the reduction of Campylobacter in primary production to be most
      beneficial for human health. The aim of this study was to test the efficacy of a
      bacteriophage application under commercial conditions which had proved to be
      effective in previous noncommercial studies under controlled experimental
      conditions. A phage cocktail for Campylobacter reduction was tested on three
      commercial broiler farms each with a control and an experimental group.
      Colonization of Campylobacter was confirmed prior to phage application in fecal
      samples. Subsequently, a phage cocktail was applied via drinking water in the
      experimental group (log10 5.8 to 7.5 PFU/bird). One day after phage application,
      Campylobacter counts of one experimental group were reduced under the detection
      limit (<50 CFU/g, P=0.0140) in fecal samples. At slaughter, a significant
      reduction of >log10 3.2 CFU/g cecal content compared to the control was still
      detected (P=0.0011). No significant reduction was observed in the experimental
      groups of the other trials. However, a significant drop in cecal Campylobacter
      counts occurred in a phage-contaminated control. These results suggest that
      maximum reduction of Campylobacter at the slaughterhouse might be achieved by
      phage application 1 to 4 days prior to slaughter.

PMID- 24077702
TI  - Composite bacterial hopanoids and their microbial producers across oxygen
      gradients in the water column of the California Current.
AB  - Hopanoids are pentacyclic triterpenoid lipids produced by many prokaryotes as
      cell membrane components. The structural variations of composite hopanoids, or
      bacteriohopanepolyols (BHPs), produced by various bacterial genera make them
      potentially useful molecular biomarkers of bacterial communities and metabolic
      processes in both modern and ancient environments. Building on previous work
      suggesting that organisms in low-oxygen environments are important contributors
      to BHP production in the marine water column and that there may be physiological
      roles for BHPs specific to these environments, this study investigated the
      relationship between trends in BHP structural diversity and abundance and the
      genetic diversity of BHP producers for the first time in a low-oxygen environment
      of the Eastern Tropical North Pacific. Amplification of the hopanoid biosynthesis
      gene for squalene hopene cyclase (sqhC) indicated far greater genetic diversity
      than would be predicted by examining BHP structural diversity alone and that
      greater sqhC genetic diversity exists in the marine environment than is
      represented by cultured representatives and most marine metagenomes. In addition,
      the genetic relationships in this data set suggest microaerophilic environments
      as potential "hot spots" of BHP production. Finally, structural analysis of BHPs
      showed that an isomer of the commonly observed BHP bacteriohopanetetrol may be
      linked to a producer that is more abundant in low-oxygen environments. Results of
      this study increase the known diversity of BHP producers and provide a detailed
      phylogeny with implications for the role of hopanoids in modern bacteria, as well
      as the evolutionary history of hopanoid biosynthesis, both of which are important
      considerations for future interpretations of the marine sedimentary record. 

PMID- 24077704
TI  - Cooperative degradation of chitin by extracellular and cell surface-expressed
      chitinases from Paenibacillus sp. strain FPU-7.
AB  - Chitin, a major component of fungal cell walls and invertebrate cuticles, is an
      exceedingly abundant polysaccharide, ranking next to cellulose. Industrial demand
      for chitin and its degradation products as raw materials for fine chemical
      products is increasing. A bacterium with high chitin-decomposing activity,
      Paenibacillus sp. strain FPU-7, was isolated from soil by using a screening
      medium containing alpha-chitin powder. Although FPU-7 secreted several
      extracellular chitinases and thoroughly digested the powder, the extracellular
      fluid alone broke them down incompletely. Based on expression cloning and
      phylogenetic analysis, at least seven family 18 chitinase genes were found in the
      FPU-7 genome. Interestingly, the product of only one gene (chiW) was identified
      as possessing three S-layer homology (SLH) domains and two glycosyl hydrolase
      family 18 catalytic domains. Since SLH domains are known to function as anchors
      to the Gram-positive bacterial cell surface, ChiW was suggested to be a novel
      multimodular surface-expressed enzyme and to play an important role in the
      complete degradation of chitin. Indeed, the ChiW protein was localized on the
      cell surface. Each of the seven chitinase genes (chiA to chiF and chiW) was
      cloned and expressed in Escherichia coli cells for biochemical characterization
      of their products. In particular, ChiE and ChiW showed high activity for
      insoluble chitin. The high chitinolytic activity of strain FPU-7 and the
      chitinases may be useful for environmentally friendly processing of chitin in the
      manufacture of food and/or medicine. 

PMID- 24077705
TI  - A novel Rickettsia species detected in Vole Ticks (Ixodes angustus) from Western
      Canada.
AB  - The genomic DNA of ixodid ticks from western Canada was tested by PCR for the
      presence of Rickettsia. No rickettsiae were detected in Ixodes sculptus, whereas
      18% of the I. angustus and 42% of the Dermacentor andersoni organisms examined
      were PCR positive for Rickettsia. The rickettsiae from each tick species were
      characterized genetically using multiple genes. Rickettsiae within the D.
      andersoni organisms had sequences at four genes that matched those of R.
      peacockii. In contrast, the Rickettsia present within the larvae, nymphs, and
      adults of I. angustus had novel DNA sequences at four of the genes characterized
      compared to the sequences available from GenBank for all recognized species of
      Rickettsia and all other putative species within the genus. Phylogenetic analyses
      of the sequence data revealed that the rickettsiae in I. angustus do not belong
      to the spotted fever, transitional, or typhus groups of rickettsiae but are most
      closely related to "Candidatus Rickettsia kingi" and belong to a clade that also
      includes R. canadensis, "Candidatus Rickettsia tarasevichiae," and "Candidatus
      Rickettsia monteiroi." 

PMID- 24077706
TI  - Iterative saturation mutagenesis of -6 subsite residues in cyclodextrin
      glycosyltransferase from Paenibacillus macerans to improve maltodextrin
      specificity for 2-O-D-glucopyranosyl-L-ascorbic acid synthesis.
AB  - 2-O-d-Glucopyranosyl-l-ascorbic acid (AA-2G), a stable l-ascorbic acid
      derivative, is usually synthesized by cyclodextrin glycosyltransferase (CGTase),
      which contains nine substrate-binding subsites (from +2 to -7). In this study,
      iterative saturation mutagenesis (ISM) was performed on the -6 subsite residues
      (Y167, G179, G180, and N193) in the CGTase from Paenibacillus macerans to improve
      its specificity for maltodextrin, which is a cheap and easily soluble glycosyl
      donor for AA-2G synthesis. Site saturation mutagenesis of four sites-Y167, G179,
      G180, and N193-was first performed and revealed that four mutants-Y167S, G179R,
      N193R, and G180R-produced AA-2G yields higher than those of other mutant and wild
      type CGTases. ISM was then conducted with the best positive mutant as a template.
      Under optimal conditions, mutant Y167S/G179K/N193R/G180R produced the highest AA
      2G titer of 2.12 g/liter, which was 84% higher than that (1.15 g/liter) produced
      by the wild-type CGTase. Kinetics analysis of AA-2G synthesis using mutant
      CGTases confirmed the enhanced maltodextrin specificity and showed that compared
      to the wild-type CGTase, the mutants had no cyclization activity but high
      hydrolysis and disproportionation activities. A possible mechanism for the
      enhanced substrate specificity was also analyzed through structure modeling of
      the mutant and wild-type CGTases. These results indicated that the -6 subsite
      played crucial roles in the substrate binding and catalytic reactions of CGTase
      and that the obtained CGTase mutants, especially Y167S/G179K/N193R/G180R, are
      promising starting points for further development through protein engineering. 

PMID- 24077707
TI  - Rapid transposon liquid enrichment sequencing (TnLE-seq) for gene fitness
      evaluation in underdeveloped bacterial systems.
AB  - Whole-genome fitness analysis in microbes that uses saturating transposon
      mutagenesis combined with massively parallel sequencing (Tn-seq) is providing a
      measure of the contribution of each gene to a given growth condition. With this
      technique, gene fitness profiles and essential genes are discovered by
      simultaneous analyses of whether the absence of each gene product alters the
      growth kinetics of the bacterium. Here we modify the standard Tn-seq procedure to
      simplify and shorten the process by including delivery of the transposon through
      conjugation and liquid culture enrichment of the mutant pool, creating transposon
      liquid enrichment sequencing (TnLE-seq). To illustrate the success of these
      modifications and the robustness of the procedure, analyses of gene fitness of
      two cultures of the strictly anaerobic bacterium Desulfovibrio vulgaris
      Hildenborough were performed, with growth on lactate as the electron donor and
      sulfate as the electron acceptor. These data demonstrate reproducibility and
      provide a base condition for analysis of fitness changes in deletion mutants and
      in various growth conditions. The procedural modifications will facilitate the
      application of this powerful genetic analysis to microbes lacking a facile
      genetic system. Pilot studies produced 2.5*10(5) and 3.4*10(5) unique insertion
      mutants in the anaerobe Desulfovibrio vulgaris Hildenborough grown under typical
      laboratory conditions in rich medium. These analyses provided two similar high
      resolution maps of gene fitness across the genome, and the method was also
      applied to growth in minimal medium. These results were also compared to the
      coverage obtained with a ca. 13,000-member cataloged transposon library
      constructed by sequencing transposon insertion sites in individual mutants.

PMID- 24077708
TI  - Interactions between Bifidobacterium and Bacteroides species in cofermentations
      are affected by carbon sources, including exopolysaccharides produced by
      bifidobacteria.
AB  - Cocultures of strains from two Bifidobacterium and two Bacteroides species were
      performed with exopolysaccharides (EPS) previously purified from bifidobacteria,
      with inulin, or with glucose as the carbon source. Bifidobacterium longum NB667
      and Bifidobacterium breve IPLA20004 grew in glucose but showed poor or no growth
      in complex carbohydrates (inulin, EPS E44, and EPS R1), whereas Bacteroides grew
      well in the four carbon sources tested. In the presence of glucose, the growth of
      Bacteroides thetaiotaomicron DSM-2079 was inhibited by B. breve, whereas it
      remained unaffected in the presence of B. longum. Ba. fragilis DSM-2151
      contributed to a greater survival of B. longum, promoting changes in the
      synthesis of short-chain fatty acids (SCFA) and organic acids in coculture with
      respect to monocultures. In complex carbohydrates, cocultures of bifidobacterium
      strains with Ba. thetaiotaomicron did not modify the behavior of Bacteroides nor
      improve the poor growth of bifidobacteria. The metabolic activity of Ba. fragilis
      in coculture with bifidobacteria was not affected by EPS, but greater survival of
      bifidobacteria at late stages of incubation occurred in cocultures than in
      monocultures, leading to a higher production of acetic acid than in monocultures.
      Therefore, cocultures of Bifidobacterium and Bacteroides can behave differently
      against fermentable carbohydrates as a function of the specific characteristics
      of the strains from each species. These results stress the importance of
      considering specific species and strain interactions and not simply higher
      taxonomic divisions in the relationship among intestinal microbial populations
      and their different responses to probiotics and prebiotics. 

PMID- 24077709
TI  - Occurrence of potentially human-pathogenic Escherichia coli O103 in Norwegian
      sheep.
AB  - The investigation of an outbreak of hemorrhagic-uremic syndrome in Norway in 2006
      indicated that the outbreak strain Escherichia coli O103:H25 could originate from
      sheep. A national survey of the Norwegian sheep population was performed, with
      the aim of identifying and describing a possible reservoir of potentially human
      pathogenic E. coli O103, in particular of the H types 2 and 25. The investigation
      of fecal samples from 585 sheep flocks resulted in 1,222 E. coli O103 isolates
      that were analyzed for the presence of eae and stx genes, while a subset of 369
      isolates was further examined for flagellar antigens (H typing), stx subtypes,
      bfpA, astA, and molecular typing by pulsed-field gel electrophoresis (PFGE). The
      total ovine E. coli O103 serogroup was genetically diverse by numbers of H types,
      virulotypes, and PFGE banding patterns identified, although a tendency of
      clustering toward serotypes was seen. The flocks positive for potentially human
      pathogenic E. coli O103 were geographically widely distributed, and no
      association could be found with county or geographical region. The survey showed
      that eae-negative, stx-negative E. coli O103, probably nonpathogenic to humans,
      is very common in sheep, with 27.5% of flocks positive. Moreover, the study
      documented a low prevalence (0.7%) of potentially human-pathogenic Shiga toxin
      producing E. coli O103:H2, while STEC O103:H25 was not detected. However, 3.1%
      and 5.8% of the flocks were positive for enteropathogenic E. coli O103 belonging
      to H types 2 and 25, respectively. These isolates are of concern as potential
      human pathogens by themselves but more importantly as possible precursors for
      human-pathogenic STEC. 

PMID- 24077710
TI  - Cell size distributions of soil bacterial and archaeal taxa.
AB  - Cell size is a key ecological trait of soil microorganisms that determines a wide
      range of life history attributes, including the efficiency of nutrient
      acquisition. However, because of the methodological issues associated with
      determining cell sizes in situ, we have a limited understanding of how cell
      abundances vary across cell size fractions and whether certain microbial taxa
      have consistently smaller cells than other taxa. In this study, we extracted
      cells from three distinct soils and fractionated them into seven size ranges (5
      MUm to 0.2 MUm) by filtration. Cell abundances in each size fraction were
      determined by direct microscopy, with the taxonomic composition of each size
      fraction determined by high-throughput sequencing of the 16S rRNA gene. Most of
      the cells were smaller than cells typically grown in culture, with 59 to 67% of
      cells <1.2 MUm in diameter. Furthermore, each size fraction harbored distinct
      bacterial and archaeal communities in each of the three soils, and many of the
      taxa exhibited distinct size distribution patterns, with the smaller size
      fractions having higher relative abundances of taxa that are rare or poorly
      characterized (including Acidobacteria, Gemmatimonadetes, Crenarchaeota,
      Verrucomicrobia, and Elusimicrobia). In general, there was a direct relationship
      between average cell size and culturability, with those soil taxa that are poorly
      represented in culture collections tending to be smaller. Size fractionation not
      only provides important insight into the life history strategies of soil
      microbial taxa but also is a useful tool to enable more focused investigations
      into those taxa that remain poorly characterized. 

PMID- 24077711
TI  - Catabolism of glucose and lactose in Bifidobacterium animalis subsp. lactis,
      studied by 13C Nuclear Magnetic Resonance.
AB  - Bifidobacteria are widely used as probiotics in several commercial products;
      however, to date there is little knowledge about their carbohydrate metabolic
      pathways. In this work, we studied the metabolism of glucose and lactose in the
      widely used probiotic strain Bifidobacterium animalis subsp. lactis BB-12 by in
      vivo (13)C nuclear magnetic resonance (NMR) spectroscopy. The metabolism of [1
      (13)C]glucose was characterized in cells grown in glucose as the sole carbon
      source. Moreover, the metabolism of lactose specifically labeled with (13)C on
      carbon 1 of the glucose or the galactose moiety was determined in suspensions of
      cells grown in lactose. These experiments allowed the quantification of some
      intermediate and end products of the metabolic pathways, as well as determination
      of the consumption rate of carbon sources. Additionally, the labeling patterns in
      metabolites derived from the metabolism of glucose specifically labeled with
      (13)C on carbon 1, 2, or 3 in cells grown in glucose or lactose specifically
      labeled in carbon 1 of the glucose moiety ([1-(13)Cglucose]lactose), lactose
      specifically labeled in carbon 1 of the galactose moiety ([1
      (13)Cgalactose]lactose), and [1-(13)C]glucose in lactose-grown cells were
      determined in cell extracts by (13)C NMR. The NMR analysis showed that the
      recovery of carbon was fully compatible with the fructose 6-phosphate, or bifid,
      shunt. The activity of lactate dehydrogenase, acetate kinase, fructose 6
      phosphate phosphoketolase, and pyruvate formate lyase differed significantly
      between glucose and lactose cultures. The transcriptional analysis of several
      putative glucose and lactose transporters showed a significant induction of
      Balat_0475 in the presence of lactose, suggesting a role for this protein as a
      lactose permease. This report provides the first in vivo experimental evidence of
      the metabolic flux distribution in the catabolic pathway of glucose and lactose
      in bifidobacteria and shows that the bifid shunt is the only pathway involved in
      energy recruitment from these two sugars. On the basis of our experimental
      results, a model of sugar metabolism in B. animalis subsp. lactis is proposed. 

PMID- 24077712
TI  - Glycerol-3-phosphate Acyltransferase contributes to triacylglycerol biosynthesis,
      lipid droplet formation, and host invasion in Metarhizium robertsii.
AB  - Enzymes involved in the triacylglycerol (TAG) biosynthesis have been well studied
      in the model organisms of yeasts and animals. Among these, the isoforms of
      glycerol-3-phosphate acyltransferase (GPAT) redundantly catalyze the first and
      rate-limiting step in glycerolipid synthesis. Here, we report the functions of
      mrGAT, a GPAT ortholog, in an insect-pathogenic fungus, Metarhizium robertsii.
      Unlike in yeasts and animals, a single copy of the mrGAT gene is present in the
      fungal genome and the gene deletion mutant is viable. Compared to the wild type
      and the gene-rescued mutant, the DeltamrGAT mutant demonstrated reduced abilities
      to produce conidia and synthesize TAG, glycerol, and total lipids. More
      importantly, we found that mrGAT is localized to the endoplasmic reticulum and
      directly linked to the formation of lipid droplets (LDs) in fungal cells. Insect
      bioassay results showed that mrGAT is required for full fungal virulence by
      aiding fungal penetration of host cuticles. Data from this study not only advance
      our understanding of GPAT functions in fungi but also suggest that filamentous
      fungi such as M. robertsii can serve as a good model to elucidate the role of the
      glycerol phosphate pathway in fungal physiology, particularly to determine the
      mechanistic connection of GPAT to LD formation. 

PMID- 24077713
TI  - Risk factors associated with Salmonella and Listeria monocytogenes contamination
      of produce fields.
AB  - Identification of management practices associated with preharvest pathogen
      contamination of produce fields is crucial to the development of effective Good
      Agricultural Practices (GAPs). A cross-sectional study was conducted to (i)
      determine management practices associated with a Salmonella- or Listeria
      monocytogenes-positive field and (ii) quantify the frequency of these pathogens
      in irrigation and nonirrigation water sources. Over 5 weeks, 21 produce farms in
      New York State were visited. Field-level management practices were recorded for
      263 fields, and 600 environmental samples (soil, drag swab, and water) were
      collected and analyzed for Salmonella and L. monocytogenes. Management practices
      were evaluated for their association with the presence of a pathogen-positive
      field. Salmonella and L. monocytogenes were detected in 6.1% and 17.5% of fields
      (n = 263) and 11% and 30% of water samples (n = 74), respectively. The majority
      of pathogen-positive water samples were from nonirrigation surface water sources.
      Multivariate analysis showed that manure application within a year increased the
      odds of a Salmonella-positive field (odds ratio [OR], 16.7), while the presence
      of a buffer zone had a protective effect (OR, 0.1). Irrigation (within 3 days of
      sample collection) (OR, 6.0), reported wildlife observation (within 3 days of
      sample collection) (OR, 6.1), and soil cultivation (within 7 days of sample
      collection) (OR, 2.9) all increased the likelihood of an L. monocytogenes
      positive field. Our findings provide new data that will assist growers with
      science-based evaluation of their current GAPs and implementation of preventive
      controls that reduce the risk of preharvest contamination. 

PMID- 24077714
TI  - Abilities of the mCP Agar method and CRENAME alpha toxin-specific real-time PCR
      assay to detect Clostridium perfringens spores in drinking water.
AB  - We first determined the analytical specificity and ubiquity (i.e., the ability to
      detect all or most strains) of a Clostridium perfringens-specific real-time PCR
      (rtPCR) assay based on the cpa gene (cpa rtPCR) by using a bacterial strain panel
      composed of C. perfringens and non-C. perfringens Clostridium strains. All non-C.
      perfringens Clostridium strains tested negative, whereas all C. perfringens
      strains tested positive with the cpa rtPCR, for an analytical specificity and
      ubiquity of 100%. The cpa rtPCR assay was then used to confirm the identity of
      116 putative C. perfringens isolates recovered after filtration of water samples
      and culture on mCP agar. Colonies presenting discordant results between the
      phenotype on mCP agar and cpa rtPCR were identified by sequencing the 16S rRNA
      and cpa genes. Four mCP(-)/rtPCR(+) colonies were identified as C. perfringens,
      whereas 3 mCP(+)/rtPCR(-) colonies were identified as non-C. perfringens. The cpa
      rtPCR was negative with all 51 non-C. perfringens strains and positive with 64 of
      65 C. perfringens strains. Finally, we compared mCP agar and a CRENAME
      (concentration and recovery of microbial particles, extraction of nucleic acids,
      and molecular enrichment) procedure plus cpa rtPCR (CRENAME + cpa rtPCR) for
      their abilities to detect C. perfringens spores in drinking water. CRENAME + cpa
      rtPCR detected as few as one C. perfringens CFU per 100 ml of drinking water
      sample in less than 5 h, whereas mCP agar took at least 25 h to deliver results.
      CRENAME + cpa rtPCR also allows the simultaneous and sensitive detection of
      Escherichia coli and C. perfringens from the same potable water sample. In
      itself, it could be used to assess the public health risk posed by drinking water
      potentially contaminated with pathogens more resistant to disinfection. 

PMID- 24077715
TI  - Insecticidal activity of Bacillus thuringiensis Cry1Bh1 against Ostrinia
      nubilalis (Hubner) (Lepidoptera: Crambidae) and other lepidopteran pests.
AB  - Bacillus thuringiensis is an important source of insect resistance traits in
      commercial crops. In an effort to prolong B. thuringiensis trait durability,
      insect resistance management programs often include combinations of insecticidal
      proteins that are not cross resistant or have demonstrable differences in their
      site of action as a means to mitigate the development of resistant insect
      populations. In this report, we describe the activity spectrum of a novel B.
      thuringiensis Cry protein, Cry1Bh1, against several lepidopteran pests, including
      laboratory-selected B. thuringiensis-resistant strains of Ostrinia nubilalis and
      Heliothis virescens and progeny of field-evolved B. thuringiensis-resistant
      strains of Plutella xylostella and Spodoptera frugiperda. Cry1Bh1 is active
      against susceptible and B. thuringiensis-resistant colonies of O. nubilalis, P.
      xylostella, and H. virescens in laboratory diet-based assays, implying a lack of
      cross-resistance in these insects. However, Cry1Bh1 is not active against
      susceptible or Cry1F-resistant S. frugiperda. Further, Cry1Bh1 does not compete
      with Cry1Fa or Cry1Ab for O. nubilalis midgut brush border membrane binding
      sites. Cry1Bh1-expressing corn, while not completely resistant to insect damage,
      provided significantly better leaf protection against Cry1Fa-resistant O.
      nubilalis than did Cry1Fa-expressing hybrid corn. The lack of cross-resistance
      with Cry1Ab and Cry1Fa along with independent membrane binding sites in O.
      nubilalis makes Cry1Bh1 a candidate to further optimize for in-plant resistance
      to this pest. 

PMID- 24077716
TI  - Use of a hierarchical oligonucleotide primer extension approach for multiplexed
      relative abundance analysis of methanogens in anaerobic digestion systems.
AB  - In this study, we established a rapid multiplex method to detect the relative
      abundances of amplified 16S rRNA genes from known cultivatable methanogens at
      hierarchical specificities in anaerobic digestion systems treating industrial
      wastewater and sewage sludge. The method was based on the hierarchical
      oligonucleotide primer extension (HOPE) technique and combined with a set of 27
      primers designed to target the total archaeal populations and methanogens from 22
      genera within 4 taxonomic orders. After optimization for their specificities and
      detection sensitivity under the conditions of multiple single-nucleotide primer
      extension reactions, the HOPE approach was applied to analyze the methanogens in
      19 consortium samples from 7 anaerobic treatment systems (i.e., 513 reactions).
      Among the samples, the methanogen populations detected with order-level primers
      accounted for >77.2% of the PCR-amplified 16S rRNA genes detected using an
      Archaea-specific primer. The archaeal communities typically consisted of 2 to 7
      known methanogen genera within the Methanobacteriales, Methanomicrobiales, and
      Methanosarcinales and displayed population dynamic and spatial distributions in
      anaerobic reactor operations. Principal component analysis of the HOPE data
      further showed that the methanogen communities could be clustered into 3
      distinctive groups, in accordance with the distribution of the Methanosaeta,
      Methanolinea, and Methanomethylovorans, respectively. This finding suggested that
      in addition to acetotrophic and hydrogenotrophic methanogens, the methylotrophic
      methanogens might play a key role in the anaerobic treatment of industrial
      wastewater. Overall, the results demonstrated that the HOPE approach is a
      specific, rapid, and multiplexing platform to determine the relative abundances
      of targeted methanogens in PCR-amplified 16S rRNA gene products. 

PMID- 24077717
TI  - Effect of incubation temperature on the detection of thermophilic campylobacter
      species from freshwater beaches, nearby wastewater effluents, and bird fecal
      droppings.
AB  - This large-scale study compared incubation temperatures (37 degrees C versus 42
      degrees C) to study the detection of thermophilic Campylobacter species,
      including Campylobacter jejuni, C. coli, and C. lari, in various surface water
      samples and bird fecal droppings around Hamilton Harbor, Lake Ontario. The
      putative culture isolates obtained from incubation temperatures of 37 and 42
      degrees C were confirmed by Campylobacter genus- and species-specific triplex PCR
      assays targeting the 16S rRNA gene and the 16S-23S rRNA gene internal transcribed
      spacer (ITS) region. A total of 759 water, wastewater, and bird fecal dropping
      samples were tested. Positive amplification reactions for the genus Campylobacter
      were found for 454 (60%) samples incubated at 37 degrees C, compared to 258 (34%)
      samples incubated at 42 degrees C. C. jejuni (16%) and C. lari (12%) were
      detected significantly more frequently at the 42 degrees C incubation temperature
      than at 37 degrees C (8% and 5%, respectively). In contrast, significantly higher
      rates of C. coli (14%) and other Campylobacter spp. (36%) were detected at the 37
      degrees C incubation temperature than at 42 degrees C (8% and 7%, respectively).
      These results were consistent across surface water, wastewater, and bird fecal
      dropping samples. At times, Campylobacter spp. were recovered and detected at 37
      degrees C (3% for C. jejuni, 10% for C. coli, and 3% for C. lari) when the same
      samples incubated at 42 degrees C were negative. A significantly higher rate of
      other Campylobacter spp. was detected only at 37 degrees C (32%) than only at 42
      degrees C (3%). These results indicate that incubation temperature can
      significantly influence the culturability and detection of thermophilic and other
      fastidious Campylobacter spp. and that a comprehensive characterization of the
      Campylobacter spp. in surface water, wastewaters, or bird fecal droppings will
      require incubation at both 37 and 42 degrees C. 

PMID- 24077719
TI  - Arachnoid cyst accompanied by proptosis and unilateral  high myopia.
AB  - An 8-year-old boy presented with proptosis of the left eye. On ophthalmic
      examination,unilateral axial elongation of the left eye was evident.Computed
      tomography and magnetic resonance imaging revealed an arachnoid cyst in the left
      middle cranial fossa, which expanded the bone and deformed the posterolateral
      wall of the left orbit. The lesion was observed with serial examinations and
      reviewed by a neurosurgeon and a radiologist. After 6 months of follow-up, there
      was no progression of the cyst. We believe this is the youngest reported case of
      an arachnoid cyst associated with isolated proptosis in the setting of unilateral
      high myopia. Neuroimaging should be considered in cases of prominent or
      progressive proptosis in the context of unilateral axial myopia in order to
      detect other possible etiologies.

PMID- 24077718
TI  - DNA double-strand break repair at--15{degrees}C.
AB  - The survival of microorganisms in ancient glacial ice and permafrost has been
      ascribed to their ability to persist in a dormant, metabolically inert state. An
      alternative possibility, supported by experimental data, is that microorganisms
      in frozen matrices are able to sustain a level of metabolic function that is
      sufficient for cellular repair and maintenance. To examine this experimentally,
      frozen populations of Psychrobacter arcticus 273-4 were exposed to ionizing
      radiation (IR) to simulate the damage incurred from natural background IR sources
      in the permafrost environment from over ~225 kiloyears (ky). High-molecular
      weight DNA was fragmented by exposure to 450 Gy of IR, which introduced an
      average of 16 double-strand breaks (DSBs) per chromosome. During incubation at 
      15 degrees C for 505 days, P. arcticus repaired DNA DSBs in the absence of net
      growth. Based on the time frame for the assembly of genomic fragments by P.
      arcticus, the rate of DNA DSB repair was estimated at 7 to 10 DSBs year(-1) under
      the conditions tested. Our results provide direct evidence for the repair of DNA
      lesions, extending the range of complex biochemical reactions known to occur in
      bacteria at frozen temperatures. Provided that sufficient energy and nutrient
      sources are available, a functional DNA repair mechanism would allow cells to
      maintain genome integrity and augment microbial survival in icy terrestrial or
      extraterrestrial environments. 

PMID- 24077721
TI  - Effects of bovine lactoferrin to oral Candida albicans and Candida glabrata
      isolates recovered from the saliva in elderly people.
AB  - The effects of bovine lactoferrin (bLF) on the growth of Candida species and on
      inflammatory cytokine production in gingival keratinocytes, NDUSD-1 co-cultured
      with Candida strains were investigated. The results showed that bLF at 10 and 100
      MUg/mL significantly inhibits the growth of two C. albicans strains and two C.
      glabrata strains isolated from the saliva of elderly people requiring nursing
      care, respectively. The levels of inflammatory cytokines, interleukin (IL)-6, and
      IL-8 in NDUSD-1 co-cultured with each of these four Candida strains were
      measured. C. albicans tend to have a more potent capacity than C. glabrata to
      induce the production of the inflammatory cytokines in NDUSD-1. The levels of IL
      6 and IL-8 in NDUSD-1 co-cultured with each of Candida species were measured
      after addition of bLF. bLF at concentrations from 1 to 100 MUg/mL significantly
      inhibited the production of these cytokines in NDUSD-1 co-cultured with Candida
      species. These findings suggest that bLF may be useful in reducing the risk of
      aspiration pneumonia among elderly people requiring care for whom oral care is
      difficult.

PMID- 24077720
TI  - Transient increase of retinal nerve fiber layer thickness  after macular hole
      surgery.
AB  - We studied the changes in the thickness of the retinal nerve fiber layer (RNFL)
      after surgery for idiopathic macular hole (MH) using spectral-domain optical
      coherence tomography (SD-OCT). Twenty eyes of 20 consecutive patients who
      underwent vitrectomy to close a MH were studied. The peripapillary RNFL thickness
      was measured by SD-OCT before and at 1, 3, and 6 months after surgery. The mean
      overall thickness, the thickness of the four quadrants, and the thickness of each
      of the 12 clock hours of the RNFL were analyzed. The mean overall RNFL thickness
      before surgery was 93.3 +/- 9.6 lm,and it increased significantly to 98.7 +/- 7.4
      lm at 1 month after surgery (P?0.05). The mean overall thickness then returned to
      the pre-surgery level at three and 6 months. The transient increase of RNFL
      thickness at 1 month after surgery was statistically significant in the superior,
      nasal, and inferior quadrants. The increase in the thickness of the nasal
      quadrants was maintained for up to 6 months. When the thickness of the individual
      12 clock hours were analyzed, the transient increase of RNFL thickness at 1 month
      after surgery was significant at each of the 0-5 o'clock positions. The transient
      increase in the RNFL thickness after MH surgery may be caused by mild edema of
      the inner retinal layers caused by the MH surgery.

PMID- 24077722
TI  - Self-eating to grow and kill: autophagy in filamentous ascomycetes.
AB  - Autophagy is a tightly controlled degradation process in which eukaryotic cells
      digest their own cytoplasm containing protein complexes and organelles in the
      vacuole or lysosome. Two types of autophagy have been described: macroautophagy
      and microautophagy. Both types can be further divided into nonselective and
      selective processes. Molecular analysis of autophagy over the last two decades
      has mostly used the unicellular ascomycetes Saccharomyces cerevisiae and Pichia
      pastoris. Genetic analysis in these yeasts has identified 36 autophagy-related
      (atg) genes; many are conserved in all eukaryotes, including filamentous
      ascomycetes. However, the autophagic machinery also evolved significant
      differences in fungi, as a consequence of adaptation to diverse fungal
      lifestyles. Intensive studies on autophagy in the last few years have shown that
      autophagy in filamentous fungi is not only involved in nutrient homeostasis but
      in other cellular processes such as cell differentiation, pathogenicity and
      secondary metabolite production. This mini-review focuses on the specific roles
      of autophagy in filamentous fungi.

PMID- 24077723
TI  - L-amino acid oxidase as biocatalyst: a dream too far?
AB  - L-amino acid oxidase (LAAO) is a flavoenzyme containing non-covalently bound
      flavin adenine dinucleotide, which catalyzes the stereospecific oxidative
      deamination of l-amino acids to alpha-keto acids and also produces ammonia and
      hydrogen peroxide via an imino acid intermediate. LAAOs purified from snake
      venoms are the best-studied members of this family of enzymes, although a number
      of LAAOs from bacterial and fungal sources have been also reported. From a
      biochemical point of view, LAAOs from different sources are distinguished by
      molecular mass, substrate specificity, post-translational modifications and
      regulation. In analogy to the well-known biotechnological applications of d-amino
      acid oxidase, important results are expected from the availability of suitable
      LAAOs; however, these expectations have not been fulfilled yet because none of
      the "true" LAAOs has successfully been expressed as a recombinant protein in
      prokaryotic hosts, such as Escherichia coli. In enzyme biotechnology, recombinant
      production of a protein is mandatory both for the production of large amounts of
      the catalyst and to improve its biochemical properties by protein engineering. As
      an alternative, flavoenzymes active on specific l-amino acids have been
      identified, e.g., l-aspartate oxidase, l-lysine oxidase, l-phenylalanine oxidase,
      etc. According to presently available information, amino acid oxidases with
      "narrow" or "strict" substrate specificity represent as good candidates to obtain
      an enzyme more suitable for biotechnological applications by enlarging their
      substrate specificity by means of protein engineering.

PMID- 24077724
TI  - Characterization of the human dynein light chain Rp3  and its use as a non-viral
      gene delivery vector.
AB  - Dynein light chains mediate the interaction between the cargo and the dynein
      motor complex during retrograde microtubule-mediated transport in eukaryotic
      cells. In this study, we expressed and characterized the recombinant human dynein
      light chain Rp3 and developed a modified variant harboring an N-terminal DNA
      binding domain (Rp3-Db). Our approach aimed to explore the retrograde cell
      machinery based on dynein to enhance plasmid DNA (pDNA) traffic along the cytosol
      toward the nucleus. In the context of non-viral gene delivery, Rp3-Db is expected
      to simultaneously interact with DNA and dynein, thereby enabling a more rapid and
      efficient transport of the genetic material across the cytoplasm. We successfully
      purified recombinant Rp3 and obtained a low-resolution structural model using
      small-angle X-ray scattering. Additionally, we observed that Rp3 is a homodimer
      under reducing conditions and remains stable over a broad pH range. The ability
      of Rp3 to interact with the dynein intermediate chain in vitro was also observed,
      indicating that the recombinant Rp3 is correctly folded and functional. Finally,
      Rp3-Db was successfully expressed and purified and exhibited the ability to
      interact with pDNA and mediate the transfection of cultured HeLa cells. Rp3-Db
      was also capable of interacting in vitro with dynein intermediate chains,
      indicating that the addition of the N-terminal DNA-binding domain does not
      compromise its function. The transfection level observed for Rp3-Db is far
      superior than that reported for protamine and is comparable to that of the
      cationic lipid LipofectamineTM. This report presents an initial characterization
      of a non-viral delivery vector based on the dynein light chain Rp3 and
      demonstrates the potential use of modified human light chains as gene delivery
      vectors.

PMID- 24077725
TI  - Nanofiltration of polysaccharides from Agaricus subrufescens.
AB  - A simplified submerged airlift cultivation was established for the production of
      biomass from Agaricus subrufescens. In this work, soluble polysaccharides
      extracted from fungal mycelium, fruiting bodies, and the residual culture media
      were concentrated by nanofiltration. Total and high molar mass polysaccharides
      and soluble solids were determined in the concentrate for the three extracts.
      Additionally, the permeate flow, the influences of temperature and pressure, and
      the resistance to the permeate flow during filtration were also evaluated. Ayield
      of 5.5 g/L of biomass with 35%glucose conversion was obtained when 0.5 g/L of
      initial inoculum was employed. Average specific speed of growth was 0.4/day, with
      biomass productivity of about 0.76 g/(L day). Nanofiltration has yielded
      polysaccharide increases of 85, 82, and 92% in the extracts from fruiting bodies,
      mycelium, and liquid media, respectively. A reduction in the permeate flow was
      observed during filtration, and it was compensated by higher pressures and
      temperatures. The higher resistance to the permeate flux was caused by
      polarization due to concentration (polarized gel layer), reaching values of 88%
      for the culture media. Maximal resistance caused by the membrane reached values
      of 40% for the extract from the fruiting bodies. On the other hand, resistance
      caused by fouling was responsible for less than 3.5%. In conclusion,
      nanofiltration is efficient to concentrate these functional compounds extracted
      from A. subrufescens and can, therefore, be applied in different biotechnological
      areas.

PMID- 24077727
TI  - Genetic engineering of Streptomyces bingchenggensis  to produce milbemycins A3/A4
      as main components  and eliminate the biosynthesis of nanchangmycin.
AB  - Milbemycins A3/A4 are important 16-membered macrolides which have been
      commercialized and widely used as pesticide and veterinary medicine. However,
      similar to other milbemycin producers, the production of milbemycins A3/A4 in
      Streptomyces bingchenggensis is usually accompanied with undesired by-products
      such as C5-O - methylmilbemycins B2/B3 (alpha-class) and beta1/beta2 (beta-class)
      together with nanchangmycin. In order to obtain high yield milbemycins A3/A4
      producing strains that produce milbemycins A3/A4 as main components, milD, a
      putative C5-O-methyltransferase gene of S. bingchenggensis , was biofunctionally
      investigated by heterologous expression in Escherichia coli . Enzymatic analysis
      indicated that MilD can catalyze both alpha-class (A3/A4) and beta-class
      milbemycins (beta11) into C5-O-methylmilbemycins B2/B3 and beta1, respectively,
      suggesting little effect of furan ring formed between C6 and C8a on the C5-O
      methylation catalyzed by MilD. Deletion of milD gene resulted in the elimination
      of C5-Omethylmilbemycins B2/B3 and beta1/beta2 together with an increased yield
      of milbemycins A3/A4 in disruption strain BCJ13. Further disruption of the gene
      nanLD encoding loading module of polyketide synthase responsible for the
      biosynthesis of nanchangmycin led to strain BCJ36 that abolished the production
      of nanchangmycin. Importantly, mutant strain BCJ36 (DeltamilDDeltananLD) produced
      milbemycins A3/A4 as main secondary metabolites with a yield of 2312 +/- 47
      MUg/ml, which was approximately 74 % higher than that of the initial strain S.
      bingchenggensis BC-109-6 (1326 +/- 37 MUg/ml).

PMID- 24077726
TI  - Reverse-transcriptional gene expression of anammox and ammonia-oxidizing archaea
      and bacteria in soybean and rice paddy soils of Northeast China.
AB  - The relative gene expression of hydrazine oxidoreductase encoding gene (hzo) for
      anaerobic ammonium oxidizing bacteria (anammox) and ammonia monooxygenase
      encoding gene (amoA) for both ammonia-oxidizing archaea (AOA) and ammonia
      oxidizing bacteria (AOB) in Sanjiang Plain soybean and rice paddy soils of
      Northeast China was investigated by using real-time reverse-transcriptional
      quantitative PCR. Metabolically active populations of anammox, AOA, and AOB in
      rice paddy soils were evident by the presence and successful quantification of
      hzo mRNA and amoA mRNA genes. The expression ratio of amoA gene for both AOA and
      AOB varied between soybean soils and different rice paddy soils while the
      expression of hzo gene for anammox was detectable only in rice paddy soils by
      showing a diverse relative expression ratio in each soil sample. Gene expression
      of both archaeal and bacterial amoA genes in rice paddy soils differed among the
      three sampling depths, but that of hzo was not. Both archaeal and bacterial amoA
      genes showed an increase trend of expression level with continuation of rice
      paddy cultivation, but the low expression ratio of hzo gene indicated a
      relatively small contribution of anammox in overall removal of inorganic nitrogen
      through N2 even under anoxic and high nitrogen input in agriculture. Bacterial
      amoA gene from two soybean fields and three rice paddy fields were also analyzed
      for community composition by denaturing gradient gel electrophoresis fingerprint.
      Community shift was observed between soybean and paddy fields and within each of
      them. The consistent occurrence of three bands 5, 6, and 7 in all samples showed
      their high adaptability for both arid cultivation and continuous rice paddy
      cultivation. Our data suggest that AOA and AOB are playing a more important role
      in nitrogen transformation in agricultural soils in oxic or anoxic environment
      and anammox bacteria may also contribute but in a less extent to N transformation
      in these agricultural soils under anoxic condition.

PMID- 24077728
TI  - Specific aerobic granules can be developed in a completely mixed tank reactor by
      bioaugmentation using micro-mycelial pellets of Phanerochaete chrysosporium.
AB  - Aerobic granules were firstly developed in a completely mixed tank reactor (CMTR)
      by seeding micro-mycelial pellets (MMPs) of Phanerochaete chrysosporium. During
      phenol wastewater treatment, sludge granulation rate reached 67 % after 15-day
      operation. The granules in CMTR are different from aerobic granules described in
      literature in morphology, and a majority of them are rod-shaped or rodlike sludge
      besides spherical granules. The polymorphic granules, having no essential
      difference with aerobic granules previously reported, achieve advantages over
      conventional activated sludge in settling ability, biomass concentration,
      density, integrity coefficient and removal ability to phenol wastewater. The
      optimized parameters for sludge granulation in CMTR including temperature,
      inoculum quantity, rotary speed and superficial air upflow velocity are 30 
      degrees C, 5-7 g/l, 150 rpm, and 0.5 cm/s, respectively. Analysis on sludge
      granulation mechanism indicates that MMPs not only result in the formation of
      aerobic granules containing MMPs as nuclei, but also induce the formation of
      biogranules which do not have MMP at their cores. The work challenges the general
      belief that the homogenous circular flow pattern of microbial aggregates is
      necessary for aerobic sludge granulation.

PMID- 24077729
TI  - Synthesis, characterization, and DNA binding of a novel ligand and its Cu (II)
      complex.
AB  - A novel naphthalene-2,3-diamine-2-salicylaldehyde (NS) ligand and its mononuclear
      copper(II) complex (CuNS) have been synthesized and structurally characterized.
      The UV-vis absorption and emission spectra of NS showed obvious changes on
      addition of Cu2+ solution. The interaction of the compounds with calf thymus DNA
      and G-quadruplex DNA were investigated by spectroscopic methods and thermal
      melting assay. The nucleolytic cleavage activity of the compounds was
      investigated on double-stranded circular pBR322 plasmid DNA and G-quadruplex DNA
      by electrophoretic mobility shift assay. The results show that CuNS has a greater
      ability to stabilize G-quadruplex DNA over calf-thymus DNA. The cytotoxicity of
      the compounds toward HpeG2 cancer cells was also studied, and they showed
      significant potential for antineoplastic effects.

PMID- 24077731
TI  - Pharmacological treatment of depression in women with breast cancer: a systematic
      review.
AB  - The objective of this study is to review the literature on pharmacological
      treatment of depression in women with breast cancer. According to the PRISMA
      guidelines, we conducted a systematic review of randomized, controlled clinical
      trials and open label prospective studies on antidepressants effects on
      depression in women with breast cancer up to January 14, 2013. In this analysis,
      a total of 213 studies were identified, and six studies met the inclusion
      criteria. Of the six studies, three were placebo-controlled randomized controlled
      clinical trials with fluoxetine, a selective serotonin reuptake inhibitor; and
      Mianserin-a noradrenergic and specific serotonergic antidepressant. Both studies
      found that fluoxetine and mianserin significantly improved depressive symptoms
      and quality of life (QOL) compared with placebo. Conversely, desipramine, a
      tricyclic antidepressant, and the SSRI, paroxetine, showed no significant effects
      on depression compared with placebo. A double-blind, parallel group study
      comparing a tricyclic antidepressant, amitriptyline, and paroxetine showed a
      significant and comparable improvement in depression and QOL. Two open label,
      prospective studies found that escitalopram and the norepinephrine reuptake
      inhibitor, reboxetine, significantly improved depression and QOL compared with
      baseline values. In conclusion, depression is a clinical problem in patients with
      breast cancer. Pharmacological treatment with antidepressants may improve
      depression and QOL. However, the evidence is limited, and the studies are too
      heterogeneous to recommend one regimen or drug over another. Further
      antidepressant studies are needed to guide depression treatment in patients with
      breast cancer.

PMID- 24077732
TI  - Metastasis tumor-associated protein 2 enhances metastatic behavior and is
      associated with poor outcomes in estrogen receptor-negative breast cancer.
AB  - Metastasis remains a major clinical problem in breast cancer. One family of genes
      previously linked with metastasis is the metastasis tumor-associated (MTA)
      family, with members MTA1 enhancing and MTA3 inhibiting cancer metastasis. We
      have previously found that MTA2 enhances anchorage-independent growth in estrogen
      receptor alpha (ERalpha) breast cancers, and, in combination with other genes,
      performed as a predictive biomarker in ERalpha-positive breast cancer. We
      therefore hypothesized that MTA2 enhances breast cancer progression. To test
      this, cell growth, soft-agar colony formation, migration, and in vivo metastasis
      were examined in MTA2-overexpressing and Vector control transfected ERalpha
      negative breast cancer cells. Pathways regulating cell-cell interaction,
      adhesion, and signaling through the Rho pathway were also investigated. Effects
      of the inhibition of the Rho pathway using a Rho Kinase inhibitor were assessed
      in soft-agar colony formation and motility assays in MTA2-overexpressing cells.
      MTA2 expression was associated with poor prognostic markers, and levels of MTA2
      were associated with increased risk of early recurrence in retrospective
      analyses. MTA2 overexpression was associated with enhanced metastasis, and
      pathways regulating cell-cell interactions in vitro and in vivo. Most critically,
      MTA2-enhanced motility could be blocked by inhibiting Rho pathway signaling. We
      present the novel finding that MTA2 defined a subset of ERalpha-negative patients
      with a particularly poor outcome.

PMID- 24077734
TI  - Astrocytic A20 ameliorates experimental autoimmune encephalomyelitis by
      inhibiting NF-kappaB- and STAT1-dependent chemokine production in astrocytes.
AB  - Single-nucleotide polymorphisms in the tumor necrosis factor, alpha-induced
      protein 3 gene, which encodes the ubiquitin-modifying protein A20, are linked to
      susceptibility to multiple sclerosis (MS), a demyelinating autoimmune disease of
      the central nervous system (CNS). Since it is unresolved how A20 regulates MS
      pathogenesis, we examined its function in a murine model of MS, namely
      experimental autoimmune encephalomyelitis (EAE). Deletion of A20 in
      neuroectodermal cells (astrocytes, neurons, and oligodendrocytes; Nestin-Cre
      A20fl/fl mice) or selectively in astrocytes (GFAP-Cre A20fl/fl mice) resulted in
      more severe EAE as compared to control animals. In Nestin-Cre A20fl/fl and GFAP
      Cre A20fl/fl mice demyelination and recruitment of inflammatory leukocytes were
      increased as compared to A20fl/fl control mice. Importantly, numbers of
      encephalitogenic CD4+ T cells producing interferon (IFN)-gamma, interleukin (IL)
      17, and granulocyte-macrophage colony-stimulating factor (GM-CSF), respectively,
      as well as mRNA production of IFN-gamma, IL-17, tumor necrosis factor (TNF), GM
      CSF, IL-6, CXCL1, CCL2, and CXCL10 were significantly increased in spinal cords
      of Nestin-Cre A20fl/fl and GFAP-Cre A20fl/fl mice, respectively. Compared to A20
      sufficient astrocytes, A20-deficient astrocytes displayed stronger activation of
      nuclear factor kappa-light-chain enhancer of activated B cells (NF-kappaB) in
      response to TNF, IL-17, and GM-CSF, and of signal transducer and activator of
      transcription 1 (STAT1) upon IFN-gamma stimulation. Due to NF-kappaB and STAT1
      hyperactivation, A20-deficient astrocytes produced significantly more chemokines
      in response to these key encephalitogenic cytokines of autoimmune CD4+ T cells
      resulting in an amplification of CD4+ T cell recruitment to the CNS. Thus,
      astrocytic A20 is an important inhibitor of autoimmune-mediated demyelination in
      the CNS.

PMID- 24077735
TI  - Growth inhibition of Erwinia amylovora and related Erwinia species by neutralized
      short-chain fatty acids.
AB  - Short-chain fatty acids (SCFAs) are used to preserve food and could be a tool for
      control of fire blight caused by Erwinia amylovora on apple, pear and related
      rosaceous plants. Neutralized acids were added to buffered growth media at 0.5-75
      mM and tested at pHs ranging from 6.8 to 5.5. Particularly at low pH, SCFAs with
      a chain length exceeding that of acetic acid such as propionic acid were
      effective growth inhibitors of E. amylovora possibly due to uptake of free acid
      and its intracellular accumulation. We also observed high inhibition with
      monochloroacetic acid. An E. billingiae strain was as sensitive to the acids as
      E. amylovora or E. tasmaniensis. Fire blight symptoms on pear slices were reduced
      when the slices were pretreated with neutralized propionic acid. Propionic acid
      is well water soluble and could be applied in orchards as a control agent for
      fire blight.

PMID- 24077736
TI  - Estrogen response in luminal breast cancer.

PMID- 24077737
TI  - Stromal interaction molecule 1 (STIM1) regulates sarcoplasmic/endoplasmic
      reticulum Ca2+-ATPase 1a (SERCA1a) in skeletal muscle.
AB  - Stromal interaction molecule 1 (STIM1) mediates Ca2+ movements from the
      extracellular space to the cytosol through a store-operated Ca2+ entry (SOCE)
      mechanism in various cells including skeletal muscle cells. In the present study,
      to reveal the unidentified functional role of the STIM1 C terminus from 449 to
      671 amino acids in skeletal muscle, binding assays and quadrupole time-of-flight
      mass spectrometry were used to identify proteins binding in this region along
      with proteins that mediate skeletal muscle contraction and relaxation. STIM1
      binds to sarcoplasmic/endoplasmic reticulum Ca2+-ATPase 1a (SERCA1a) via this
      region (called STIM1-SBR). The binding was confirmed in endogenous full-length
      STIM1 in rabbit skeletal muscle and mouse primary skeletal myotubes via co
      immunoprecipitation assay and immunocytochemistry. STIM1 knockdown in mouse
      primary skeletal myotubes decreased Ca2+ uptake from the cytosol to the
      sarcoplasmic reticulum (SR) through SERCA1a only at micromolar cytosolic Ca2+
      concentrations, suggesting that STIM1 could be required for the full activity of
      SERCA1a possibly during the relaxation of skeletal muscle. Various Ca2+ imaging
      experiments using myotubes expressing STIM1-SBR suggest that STIM1 is involved in
      intracellular Ca2+ distributions between the SR and the cytosol via regulating
      SERCA1a activity without affecting SOCE. Therefore, in skeletal muscle, STIM1
      could play an important role in regulating Ca2+ movements between the SR and the
      cytosol.

PMID- 24077739
TI  - Students with autism spectrum disorder in the university context: peer acceptance
      predicts intention to volunteer.
AB  - With growing numbers of individuals with autism spectrum disorder (ASD) entering
      post-secondary institutions, strategies are needed to facilitate the social
      integration of these students. The goal of this study was to examine the role of
      various factors in university students' acceptance of, and intention to volunteer
      with, a peer with ASD. Both contact quantity and quality emerged as significant
      predictors of acceptance; however, for those who had experienced direct contact
      with individuals with ASD, only perceived quality emerged as significant.
      Moreover, acceptance played a significant role in participants' likelihood of
      signing up to volunteer. These findings point to the central role that positive
      experiences play in attitude formation for this population.

PMID- 24077738
TI  - P4-ATPases: lipid flippases in cell membranes.
AB  - Cellular membranes, notably eukaryotic plasma membranes, are equipped with
      special proteins that actively translocate lipids from one leaflet to the other
      and thereby help generate membrane lipid asymmetry. Among these ATP-driven
      transporters, the P4 subfamily of P-type ATPases (P4-ATPases) comprises lipid
      flippases that catalyze the translocation of phospholipids from the exoplasmic to
      the cytosolic leaflet of cell membranes. While initially characterized as
      aminophospholipid translocases, recent studies of individual P4-ATPase family
      members from fungi, plants, and animals show that P4-ATPases differ in their
      substrate specificities and mediate transport of a broader range of lipid
      substrates, including lysophospholipids and synthetic alkylphospholipids. At the
      same time, the cellular processes known to be directly or indirectly affected by
      this class of transporters have expanded to include the regulation of membrane
      traffic, cytoskeletal dynamics, cell division, lipid metabolism, and lipid
      signaling. In this review, we will summarize the basic features of P4-ATPases and
      the physiological implications of their lipid transport activity in the cell.

PMID- 24077740
TI  - The Autism-Spectrum Quotient and Visual Search: Shallow and Deep Autistic
      Endophenotypes.
AB  - A high Autism-Spectrum Quotient (AQ) score (Baron-Cohen et al. in J Autism Dev
      Disord 31(1):5-17, 2001) is increasingly used as a proxy in empirical studies of
      perceptual mechanisms in autism. Several investigations have assessed perception
      in non-autistic people measured for AQ, claiming the same relationship exists
      between performance on perceptual tasks in high-AQ individuals as observed in
      autism. We question whether the similarity in performance by high-AQ individuals
      and autistics reflects the same underlying perceptual cause in the context of two
      visual search tasks administered to a large sample of typical individuals
      assessed for AQ. Our results indicate otherwise and that deploying the AQ as a
      proxy for autism introduces unsubstantiated assumptions about high-AQ
      individuals, the endophenotypes they express, and their relationship to Autistic
      Spectrum Conditions (ASC) individuals. 

PMID- 24077742
TI  - High anger expression exacerbates the relationship between age and metabolic
      syndrome.
AB  - OBJECTIVE: Building on prior work linking high anger expression to poor health,
      this cross-sectional study addressed whether anger expression exacerbated age
      related risk for metabolic syndrome in a national sample of adults, known as
      MIDUS (Midlife in the United States). METHOD: Respondents reported anger
      expression via survey assessments and completed an overnight clinic visit.
      RESULTS: Unadjusted metabolic syndrome prevalence was 40.6%. Men, less educated
      individuals, and those who reported not getting regular physical activity were at
      significantly higher risk for metabolic syndrome. Anger expression did not
      predict higher risk for metabolic syndrome in main effects models, but it
      moderated the relationship between age and metabolic syndrome. Age-associated
      risk for metabolic syndrome was significant only for adults with high anger
      expression. DISCUSSION: Among older adults, anger expression predicted higher
      prevalence of metabolic syndrome. Older adults reporting low anger expression had
      metabolic syndrome rates comparable to younger adults. Results highlight that
      failing to show the frequently observed decline in anger expression with age may
      have pernicious health concomitants.

PMID- 24077743
TI  - Age differences in the underlying mechanisms of stereotype threat effects.
AB  - OBJECTIVES: The goals of the present study were to (a) examine whether age
      differences exist in the mechanisms underlying stereotype threat effects on
      cognitive performance and (b) examine whether emotion regulation abilities may
      buffer against threat effects on performance. METHOD: Older and younger adults
      were exposed to positive or negative age-relevant stereotypes, allowing us to
      examine the impact of threat on regulatory focus and working memory. Self
      reported emotion regulation measures were completed prior to the session.
      RESULTS: Older adults' performance under threat suggested a prevention-focused
      approach to the task, indexed by increased accuracy and reduced speed. The same
      pattern was observed in younger adults, but the effects were not as strong. Age
      differences emerged when examining the availability of working memory resources
      under threat, with young adults showing decrements, whereas older adults did not.
      Emotion regulation abilities moderated threat effects in young adults but not in
      older adults. CONCLUSIONS: The results provide support for the notion that
      stereotype threat may lead to underperformance through somewhat different
      pathways in older and younger adults. Future research should further examine
      whether the underlying reason for this age difference is rooted in age-related
      improvements in emotion regulation.

PMID- 24077744
TI  - Perceived threat of Alzheimer's disease among Chinese American older adults: the
      role of Alzheimer's disease literacy.
AB  - OBJECTIVES: Guided by a Sociocultural Health Belief Model (SHBM), this study
      examined the roles of cultural beliefs of Alzheimer's disease (AD) and scientific
      knowledge of AD in influencing the perceived threat of AD in a sample of Chinese
      American older adults. METHOD: With the input from focus groups of 17 older
      Chinese volunteers, survey questionnaires were refined and then delivered through
      face-to-face interviews to 385 participants aged 55-100 in the Phoenix
      metropolitan area. RESULTS: Hierarchical regression analyses found that those
      aged 55-64 were more worried about AD than those aged 85 or older. Both cultural
      beliefs of AD and AD factual knowledge contributed to higher levels of perceived
      threat of AD. Education tended to moderate the effect of cultural beliefs of AD
      and AD knowledge on perceived threat of AD. DISCUSSIONS: Findings support
      inclusion of key factors in the SHBM relevant to perceived threat of AD and help
      enrich the understanding of AD literacy from both scientific and cultural
      perspectives. AD education programs and interventions should help address crucial
      cultural beliefs related to AD and the emotional consequences (e.g., concerns or
      fear of AD) that might be due to the exposure to AD factual knowledge,
      particularly for those with limited education.

PMID- 24077745
TI  - Predictors of anxiety and depression in people with colorectal cancer.
AB  - BACKGROUND: People living with colorectal cancer are at risk of anxiety and
      depression. We investigated what factors were most highly associated with these.
      METHODS: Four hundred and ninety-six people with colorectal cancer completed the
      Hospital Anxiety and Depression Scale (HADS). Data on functioning, symptoms,
      illness perceptions and social difficulties were collected by questionnaire. Case
      note-identified disease, treatment and co-morbidity data were recorded. Multiple
      logistic regression identified factors independently predictive of anxiety and
      depression caseness. RESULTS: Self-reported history of anxiety/depression
      predicted anxiety but not depression caseness. Depression caseness predicted
      anxiety caseness (p = 0.043), as did poorer self-reported cognitive functioning
      (p = 0.001), dyspnoea (p = 0.015) or diarrhoea (p = 0.021), reporting a high
      negative life and emotional impact (p < 0.001) and having difficulties with
      finance (p = 0.007). Having neo-adjuvant radiotherapy increased the odds of
      depression caseness (p = 0.007), as did poorer physical (p = 0.007), cognitive (p
      < 0.001) and social (p < 0.001) functioning, having constipation (p = 0.011),
      reporting a high negative life and emotional impact (p < 0.001), having
      difficulties with personal care (p = 0.022) and communicating with others (p =
      0.014). CONCLUSION: Levels of anxiety caseness were similar to those of non
      clinical samples, but depression caseness was higher, particularly in those who
      had received neo-adjuvant radiotherapy. Most factors associated with possible or
      probable depression may be modified with appropriate intervention.

PMID- 24077746
TI  - Reply to Molassiotis.

PMID- 24077747
TI  - Oral health is an important issue in end-of-life care, December 2012.

PMID- 24077749
TI  - Accuracy of acromioclavicular joint injections: letter to the editor.

PMID- 24077750
TI  - The superficial quad technique: letter to the editor.

PMID- 24077751
TI  - Perceived age discrimination in older adults.
AB  - OBJECTIVES: to examine perceived age discrimination in a large representative
      sample of older adults in England. METHODS: this cross-sectional study of over
      7,500 individuals used data from the fifth wave of the English Longitudinal Study
      of Ageing (ELSA), a longitudinal cohort study of men and women aged 52 years and
      older in England. Wave 5 asked respondents about the frequency of five everyday
      discriminatory situations. Participants who attributed any experiences of
      discrimination to their age were treated as cases of perceived age
      discrimination. Multivariable logistic regression analysis was used to estimate
      the odds ratios of experiencing perceived age discrimination in relation to
      selected sociodemographic factors. RESULTS: approximately a third (33.3%) of all
      respondents experienced age discrimination, rising to 36.8% in those aged 65 and
      over. Perceived age discrimination was associated with older age, higher
      education, lower levels of household wealth and being retired or not in
      employment. The correlates of age discrimination across the five discriminatory
      situations were similar. CONCLUSION: understanding age discrimination is vital if
      we are to develop appropriate policies and to target future interventions
      effectively. These findings highlight the scale of the challenge of age
      discrimination for older adults in England and illustrate that those groups are
      particularly vulnerable to this form of discrimination.

PMID- 24077752
TI  - Cognitive function is associated with impaired heart rate variability in ageing
      adults: the Irish longitudinal study on ageing wave one results.
AB  - OBJECTIVE: To examine the independent association between heart rate variability
      (HRV) and cognitive performance, in a nationally representative population study
      of older adults. METHODS: Cross-sectional analysis of wave 1 data from the Irish
      longitudinal study on ageing (TILDA) was performed. A subset of 4,763
      participants who underwent ECG recording during resting and paced breathing
      periods were used for the analysis. HRV indices were divided into quintiles for
      comparison of values and cognitive performance was defined using the Montreal
      cognitive assessment (MOCA) score. Multivariate linear regression was used to
      model the association between cognition and different quintiles of each HRV
      index, after adjustment for covariates. RESULTS: The mean age was 61.7 +/- 8.3
      years and 2,618 (55 %) were female. Lower quintiles of SDNN (P = 0.01-paced), LF
      (P = 0.001-paced), and LF:HF ratio (P = 0.049-paced) were significantly
      associated with lower MOCA scores (during both recording periods), independent of
      confounders. Sub-domains of MOCA responsible for the relationship were
      predominantly memory recall and language. INTERPRETATION: Reduced HRV is
      significantly associated with lower cognitive performance at a population level
      in people aged 50 and older. This further strengthens the relationship between
      autonomic dysfunction and cognitive disorders.

PMID- 24077753
TI  - 17 novel polymorphic microsatellite markers for the giant water bug, Abedus
      herberti (Belostomatidae).
AB  - The giant water bug (Abedus herberti) is a large flightless insect that is a
      keystone predator in aridland aquatic habitats. Extended droughts, possibly due
      to climate change and groundwater pumping, are causing once-perennial aquatic
      habitats to dry, resulting in serious conservation concern for some populations.
      A. herberti also exhibits exclusive male parental care, which has made it a model
      organism for studying mating systems evolution. Here we describe 17 novel
      polymorphic microsatellite loci developed for A. herberti. Number of alleles per
      locus ranged from 2 to 15, and average observed and expected heterozygosities
      were 0.579 and 0.697, respectively. These loci can successfully resolve both
      population genetic structure among sites separated by 3-100 km (FST = 0.08-0.21,
      P < 0.0001), and divergent mating strategies within local populations, making
      them highly useful for conservation genetics studies of this vulnerable species.

PMID- 24077754
TI  - Excellent side-to-side symmetry in glenoid size and shape.
AB  - OBJECTIVE: In quantifying glenoid bone loss and as a means to determine initial
      glenoid size, the abnormal glenoid is often compared with the contralateral
      normal glenoid. The assumption is that good symmetry exists between both glenoid
      surfaces with regard to size and shape. The purpose of this study is to
      critically analyze the structural symmetry of both glenoids in an objective and
      quantitative manner to ascertain the degree of symmetry present. MATERIALS AND
      METHODS: The study cohort comprised 60 subjects (35 males and 25 females) with no
      shoulder pathology or injury. Each glenoid surface was extracted from the whole
      scapular model constructed from CT data using a 3D curvature-based incremental
      watershed algorithm. Glenoid morphometric analysiswas carried out based on the 2D
      contour of the glenoid projected on the principal plane. RESULTS: There was no
      side-to-side difference in glenoid length (p =0.53), width (p =0.42), area (p
      =0.36), or circumference (p =0.73). All glenoid dimensions were larger in males
      than females (p <0.05). Point-wise curvature analysis showed no significant shape
      difference between both glenoids (all p >0.1). Regression analysis revealed a
      positive correlation (R2=0.3-0.5) between increasing age and increasing glenoid
      size. CONCLUSIONS: In normal subjects, both glenoids are highly symmetric in
      shape and size. This study provides objective and quantitative justification for
      using the normal counterlateral glenoid as a reference standard for initial
      glenoid shape in patients with unilateral glenoid bone loss.

PMID- 24077755
TI  - Society of Skeletal Radiology 2013 Annual Meeting summary.
AB  - Peer-reviewed abstracts presented at the 2013 Society of Skeletal Radiology (SSR)
      Annual Meeting were reviewed following oral presentation. Topics felt to be of
      potential interest to musculoskeletal investigators and practicing clinicians are
      highlighted in this compilation and analysis of the meeting. New concepts
      regarding musculoskeletal and spine imaging and intervention, musculoskeletal
      protocols and techniques, radiology education, and quality improvement are
      included. ePoster highlights are also presented.

PMID- 24077756
TI  - Progressive destructive bone changes in patients with cystinosis.
AB  - Nephropathic cystinosis is an autosomal recessive lysosomal storage disorder in
      which intracellular cystine accumulates. It is caused by mutations in the CTNS
      gene. Clinical manifestations include renal tubular Fanconi syndrome in the first
      year of life, rickets, hypokalaemia, polyuria, dehydration and acidosis, growth
      retardation, hypothyroidism, photophobia and renal glomerular deterioration. Late
      complications include myopathy, pancreatic insufficiency and retinal blindness.
      Skeletal manifestations described in these patients include failure to thrive,
      osteomalacia, rickets and short stature. This paper describes progressive bony
      abnormalities in three unrelated patients with nephropathic cystinosis that have
      not been reported previously.

PMID- 24077757
TI  - MMP-1 overexpression induced by IL-1beta: possible mechanism for inflammation in
      degenerative lumbar facet joint.
AB  - BACKGROUND: More and more attention has been focused on the inflammation or
      degeneration caused by biochemical factors in radiculopathy during lumbar facet
      joint degeneration. This study was designed to examine the expression and
      relationship of MMP-1/TIMP-1 and interleukin-1beta (IL-1beta), and to analyze the
      possible mechanism in degenerative lumbar facet joint disease. METHODS: Lumbar
      facet joint cartilage and synovial tissues in 36 cases of posterior lumbar
      surgery were harvested to investigate IL-1beta and MMP-1/TIMP-1 by
      immunohistochemistry and Western blot analysis. Double labeling
      immunofluorescence and real-time PCR, respectively, were used to assess the
      relationship between IL-1beta and MMP-1. RESULTS: IL-1beta and MMP-1 were low in
      the lumbar disc herniation (LDH) group, and increased markedly in the lumbar
      spinal canal stenosis (LSCS) group (P < 0.05). However, there is no significant
      difference of TIMP-1 between LDH group and LSCS group (P > 0.05). Double staining
      results indicated that IL-1beta overlapped with MMP-1 in the LSCS group.
      Moreover, real-time PCR results showed that MMP-1 mRNA in chondrocytes in vitro
      was affected in a dose- and time-dependent manner in response to IL-1beta
      stimulation. CONCLUSIONS: Overexpression of MMP-1, induced by IL-1beta, plays an
      important role in the inflammatory process of lumbar facet joint degeneration.

PMID- 24077758
TI  - Assessing patient-oriented results after revision total knee  arthroplasty.
AB  - BACKGROUND: Revision total knee arthroplasties (TKA) have been performed with
      increasing frequency over the last 25 years. METHODS: In this study, we
      retrospectively analyzed 78 patients who underwent 78 revision TKAs during the
      years 2003-2007 with an average follow-up of 81 months (range 60-108 months). All
      patients were treated with a standard rotating hinge prosthesis (TC3, DePuy,
      Warsaw, IN, USA) due to significant instability. We evaluated the postoperative
      results using the Knee Society clinical rating system and the WOMAC rating
      system. RESULTS: Clinical results revealed significant improvements in both
      scores. Complications occurred in almost one-third of the cases, with a
      reoperation rate of 26 %. CONCLUSION: Our mid-term findings show that revision
      TKAs lead to an improvement in patient-perceived outcomes of physical variables.
      While revision TKA is a useful option for patients, procedure-associated
      complications should not be neglected. During the course of the procedure, it is
      important to collect patient-oriented data and focus on responsive and valid
      scores.

PMID- 24077759
TI  - Quantitative index for deciding whether to administer  preventive anticoagulant
      therapy in osteoarthritis  patients undergoing total knee arthroplasty.
AB  - BACKGROUND: The 2008 American Academy of Orthopedic Surgeons recommended that
      surgeons assess the relative risks of venous thromboembolism and bleeding in
      patients undergoing total knee arthroplasty (TKA). In this situation, a
      quantitative index is required for deciding whether to administer preventive
      anticoagulant therapy for deep venous thrombosis (DVT). In this study, we
      investigated the risk factors for DVT after TKA. METHODS: We included 102
      patients (122 knees) who underwent primary TKA for osteoarthritis of the knee
      between October 2007 and March 2010. DVT was evaluated using lower limb venous
      ultrasonography. Cutoff values for individual risk factors were determined using
      a receiver-operating characteristic analysis, and the patients were grouped
      according to the cutoff values; the odds ratios (95% CI) were also investigated.
      The Wilcoxon signed-rank test and chi2 test were also used. RESULTS: DVT was
      positive in 25 knees (20.5%). Three risk factors for DVT after TKA were
      identified: age 76 years or older, preoperative maximum soleus vein (MAX-SV)
      diameter of 6.0 mm or greater, and preoperative D-dimer value of 1.1 MUg/dl or
      higher. The incidence of DVT was significantly higher in the group with two or
      more risk factors than in the group with one or no risk factors (p = 0.0001).
      CONCLUSIONS: Development of postoperative DVT correlated significantly with the
      presence of the following risk factors: age 76 years or older, preoperative MAX
      SV diameter of 6.0 mm or greater, and a preoperative D-dimer value of 1.1 MUg/dl
      or higher. Considering the risk-benefit ratio, avoiding preventive anticoagulant
      therapy following TKA can be an option for patients with osteoarthritis with one
      or no risk factors.

PMID- 24077760
TI  - Mammography utilization among Black and White Medicare beneficiaries in high
      breast cancer mortality US counties.
AB  - BACKGROUND: Disparities in US breast cancer mortality between older Black and
      White women have increased in the last 20 years. Regular mammography use is
      important for early detection and treatment: its utilization among older Blacks
      especially in counties with high Black mortality is of interest, but its extent
      and determinants are unknown. METHODS: We used Medicare claims for Black and
      White women 65-74 years old in 203 counties with the highest Black breast cancer
      mortality. Outcomes over 6 years were as follows: ever mammogram, i.e., C 1
      screening mammogram, and regular mammogram, i.e., C 3 mammograms. With logistic
      regressions, we examined the independent effect of race on screening controlling
      for individual- and county-level factors. RESULTS: Of 406,602 beneficiaries, 17 %
      were Black. Ever and regular mammogram was significantly lower among Blacks (51.6
      vs. 56.9 %; 32.9 vs. 43.1 %, respectively). Controlling for covariates, including
      use of cervical cancer screening, flu shots, or lipids tests, Black women were
      more likely to have ever mammogram (OR 1.23, CI 1.20-1.25), but not regular
      mammogram (OR 0.95, CI 0.93-0.97) than White women. County-level managed care
      penetration was negatively associated with ever and regular mammograms.
      CONCLUSIONS: In Medicare enrollees from these counties, breast cancer screening
      was low. Black women had same or better odds of screening than White women. Some
      health care factors, e.g., managed care, were negatively associated with
      screening. Further studies on the determinants of mammography utilization in
      older women from these counties are warranted.

PMID- 24077761
TI  - Oral contraceptive use and impact of cumulative intake of estrogen and progestin
      on risk of ovarian cancer.
AB  - PURPOSE: Oral contraceptive use decreases the risk of ovarian cancer, but no
      previous studies have assessed the impact of cumulative intake of estrogen and
      progestin on ovarian cancer risk. METHODS: We used data from a population-based
      case-control study conducted in Denmark in 1995-1999 among women aged 35-79
      years; 554 women with epithelial ovarian cancer and 1,564 age-matched controls
      were included in the analyses. Data were analyzed in multiple logistic regression
      models. RESULTS: The use of combined oral contraceptives only and the mixed use
      of combined and progestin-only pills decreased the risk of ovarian cancer, while
      no association was found with exclusive use of progestin-only pills. No major
      differences in risk were found for users of combined oral contraceptives with
      high- and low-potency estrogen and progestin. There was no effect of cumulative
      progestin intake, but decreased risks of ovarian cancer with increasing
      cumulative intake of estrogen (OR = 0.82; 95 % CI 0.67-0.99, per 100 mg estrogen)
      and increasing duration of oral contraceptive use (OR = 0.95; 95 % CI 0.92-0.98,
      per year of use) were found. No effect of cumulative estrogen intake was found,
      however, after adjustment for duration of oral contraceptive use. CONCLUSIONS:
      The protective effect of oral contraceptives against ovarian cancer may be
      sufficiently explained by duration of anovulation. This suggests that if the
      estrogen and progestin doses are sufficient to cause anovulation, a higher intake
      of estrogen or progestin confers no extra protection against ovarian cancer.

PMID- 24077765
TI  - Consultants.

PMID- 24077764
TI  - Going Green: The Role of the Green Tea Component EGCG in Chemoprevention.
AB  - Tea is one of the most consumed beverages worldwide, and green tea is the least
      processed from the buds of the Camellia sinensis plant. The most abundant
      component of green tea is (-)-epigallocatechin-3-gallate (EGCG), which has been
      the focus of many cell culture, animal and clinical trials, revealing that EGCG
      possesses antiproliferative, antimutagenic, antioxidant, antibacterial, antiviral
      and chemopreventive effects. In this review we briefly summarize the mechanism of
      action(s) of the green tea component EGCG, highlighting recent advances in the
      epigenetic regulation by EGCG. Additionally, we provide an overview of mouse
      chemoprevention studies and EGCG chemoprevention clinical trials.

PMID- 24077766
TI  - News and comment.
AB  - NATIONAL COACHES CONFERENCE. -Physicians interested in sports medicine will have
      the opportunity to learn from and mingle with several of the nation's leading
      authorities on sports-related injuries.A Medical Panel will be one of the
      features of the American Football and Basketball Conference, to be held at the
      University of Notre Dame, March 23 through 26, 1972.Among the nationally known
      medical authorities addressing thousands of football and basketball coaches,
      athletic directors, trainers, and their associates expected to attend the "Coach
      In" will be the following:Dr. James A. Nicholas, New York Jets Team Physician,
      who earlier this season operated on New York Jets quarterback Joe Namath; Dr.
      Leslie M. Bodnar, Orthopedic Consultant, Notre Dame University, and clinical
      Associate Professor of Orthopedic Surgery at Indiana University Medical College;
      Dr. Frank McCue, Team Physician, University of Virginia, and leading lecturer and
      authority on the treatment of athletic injuries.Among the topics the. 

PMID- 24077767
TI  - Have We Hatched the Addiction Egg: Reward Deficiency Syndrome Solution SystemTM
AB  - This article co-authored by a number of scientists, ASAM physicians, clinicians,
      treatment center owners, geneticists, neurobiologists, psychologists, social
      workers, criminologists, nurses, nutritionist, and students, is dedicated to all
      the people who have lost loved ones in substance-abuse and "reward deficiency
      syndrome" related tragedies. Why are we failing at reducing the incidence of 'Bad
      Behaviors'? Are we aiming at the wrong treatment targets for behavioral
      disorders? We are proposing a paradigm shift and calling it "Reward Deficiency
      Solution System" providing evidence for its adoption.

PMID- 24077768
TI  - Genomic divergence during speciation driven by adaptation to altitude.
AB  - Even though Darwin's "On the Origin of Species" implied selection being the main
      driver of species formation, the role of natural selection in speciation remains
      poorly understood. In particular, it remains unclear how selection at a few genes
      can lead to genomewide divergence and the formation of distinct species. We used
      a particularly attractive clear-cut case of recent plant ecological speciation to
      investigate the demography and genomic bases of species formation driven by
      adaptation to contrasting conditions. High-altitude Senecio aethnensis and low
      altitude S. chrysanthemifolius live at the extremes of a mountain slope on Mt.
      Etna, Sicily, and form a hybrid zone at intermediate altitudes but remain
      morphologically distinct. Genetic differentiation of these species was analyzed
      at the DNA polymorphism and gene expression levels by high-throughput sequencing
      of transcriptomes from multiple individuals. Out of ~ 18,000 genes analyzed, only
      a small number (90) displayed differential expression between the two species.
      These genes showed significantly elevated species differentiation (FST and Dxy),
      consistent with diversifying selection acting on these genes. Genomewide genetic
      differentiation of the species is surprisingly low (FST = 0.19), while ~ 200
      genes showed significantly higher (false discovery rate < 1%; mean outlier FST >
      0.6) interspecific differentiation and evidence for local adaptation.
      Diversifying selection at only a handful of loci may be enough for the formation
      and maintenance of taxonomically well-defined species, despite ongoing gene flow.
      This provides an explanation of why many closely related species (in plants, in
      particular) remain phenotypically and ecologically distinct despite ongoing
      hybridization, a question that has long puzzled naturalists and geneticists
      alike.

PMID- 24077769
TI  - The evolution of small insertions and deletions in the coding genes of Drosophila
      melanogaster.
AB  - Studies of protein evolution have focused on amino acid substitutions with much
      less systematic analysis on insertion and deletions (indels) in protein coding
      genes. We hence surveyed 7,500 genes between Drosophila melanogaster and D.
      simulans, using D. yakuba as an outgroup for this purpose. The evolutionary rate
      of coding indels is indeed low, at only 3% of that of nonsynonymous
      substitutions. As coding indels follow a geometric distribution in size and tend
      to fall in low-complexity regions of proteins, it is unclear whether selection or
      mutation underlies this low rate. To resolve the issue, we collected genomic
      sequences from an isogenic African line of D. melanogaster (ZS30) at a high
      coverage of 70* and analyzed indel polymorphism between ZS30 and the reference
      genome. In comparing polymorphism and divergence, we found that the divergence to
      polymorphism ratio (i.e., fixation index) for smaller indels (size <= 10 bp) is
      very similar to that for synonymous changes, suggesting that most of the within
      species polymorphism and between-species divergence for indels are selectively
      neutral. Interestingly, deletions of larger sizes (size >= 11 bp and <= 30 bp)
      have a much higher fixation index than synonymous mutations and 44.4% of fixed
      middle-sized deletions are estimated to be adaptive. To our surprise, this
      pattern is not found for insertions. Protein indel evolution appear to be in a
      dynamic flux of neutrally driven expansion (insertions) together with adaptive
      driven contraction (deletions), and these observations provide important insights
      for understanding the fitness of new mutations as well as the evolutionary
      driving forces for genomic evolution in Drosophila species.

PMID- 24077770
TI  - Effects of feedback on the perception of inspiratory resistance in children with
      persistent asthma: a signal detection approach.
AB  - OBJECTIVE: Accurate perception of asthma episodes increases the likelihood that
      they will be managed effectively. The purpose of the study was to examine the
      effect of feedback in a signal detection task on perception of increased airflow
      obstruction in children with persistent asthma. METHODS: The effect of feedback
      training on the perception of resistive loads was evaluated in 155 children with
      persistent asthma between 8 and 15 years of age. Each child participated in four
      experimental sessions that occurred approximately once every 2 weeks, an initial
      session followed by three training sessions. During the initial session, the
      threshold resistance to breathing was determined for each child. Subsequently,
      each child was randomly assigned to one of two resistive load training conditions
      in a signal detection paradigm: training with immediate performance feedback or
      training with no performance feedback. RESULTS: The threshold resistance to
      breathing, determined in the initial session, was equivalent between groups.
      Children in the feedback condition discriminated more accurately between both the
      presence and the absence of increases in the resistance to breathing (206 [48]
      versus 180 [39] correct responses, p < .001), and differences over time between
      groups increased reliably as a function of training (165 [40] versus 145 [32]
      correct responses, p < .001). Response times and confidence ratings were
      equivalent between groups, and no differences in breathing patterns were observed
      between conditions. CONCLUSIONS: Feedback training results in improved perception
      of respiratory sensations in children with asthma, a finding with implications
      for strategies of asthma self-management.

PMID- 24077771
TI  - Salivary nerve growth factor reactivity to acute psychosocial stress: a new
      frontier for stress research.
AB  - OBJECTIVE: Neurotrophins such as nerve growth factor (NGF) may represent a stress
      responsive system complementing the better known neuroendocrine (hypothalamic
      pituitary-adrenal axis) and autonomic nervous system, but there is little
      evidence for NGF response to acute stress in humans because noninvasive measures
      have not been available. We investigated salivary NGF (sNGF) in 40 healthy young
      adults confronting a romantic conflict stressor. METHODS: Five saliva samples-two
      collected before and three after the conflict-were assayed for sNGF, cortisol
      (hypothalamic-pituitary-adrenal marker), and alpha-amylase (sAA; ANS marker). In
      addition, a control group (n = 20) gave saliva samples at the same time intervals
      to determine whether sNGF changes were specific to the conflict stressor.
      RESULTS: sNGF showed significant reactivity from entry to the first poststress
      sample among study participants (beta = .13, p = .001), with nonsignificant
      change across poststress samples. Control participants showed no change in sNGF
      across the same period. Within-person changes in sNGF were generally aligned with
      both cortisol (beta = .17, p = .003) and sAA (beta = .17, p = .021) responses.
      Preconflict negative emotion predicted lower sNGF reactivity (beta = -.08, p =
      .009) and less alignment with sAA (beta = -.09, p = .040), whereas positive
      emotion predicted less alignment with cortisol (beta = -.10, p = .019).
      CONCLUSIONS: This study is the first to document sNGF as a marker that responds
      to stress in humans.

PMID- 24077773
TI  - Substantial expression of luteinizing hormone-releasing hormone (LHRH) receptor
      type I in human uveal melanoma.
AB  - Uveal melanoma is the most common primary intraocular malignancy in adults, with
      a very high mortality rate due to frequent liver metastases. Consequently, the
      therapy of uveal melanoma remains a major clinical challenge and new treatment
      approaches are needed. For improving diagnosis and designing a rational and
      effective therapy, it is essential to elucidate molecular characteristics of this
      malignancy. The aim of this study therefore was to evaluate as a potential
      therapeutic target the expression of luteinizing hormone-releasing hormone (LHRH)
      receptor in human uveal melanoma. The expression of LHRH ligand and LHRH receptor
      transcript forms was studied in 39 human uveal melanoma specimens by RT-PCR using
      gene specific primers. The binding charachteristics of receptors for LHRH on 10
      samples were determined by ligand competition assays. The presence of LHRH
      receptor protein was further evaluated by immunohistochemistry. The expression of
      mRNA for type I LHRH receptor was detected in 18 of 39 (46%) of tissue specimens.
      mRNA for LHRH-I ligand could be detected in 27 of 39 (69%) of the samples. Seven
      of 10 samples investigated showed high affinity LHRH-I receptors. The specific
      presence of full length LHRH receptor protein was further confirmed by
      immunohistochemistry. A high percentage of uveal melanomas express mRNA and
      protein for type-I LHRH receptors. Our results support the merit of further
      investigation of LHRH receptors in human ophthalmological tumors. Since diverse
      analogs of LHRH are in clinical trials or are already used for the treatment of
      various cancers, theseanalogs could be considered for the LHRH receptor-based
      treatment of uveal melanoma. 

PMID- 24077772
TI  - Racial differences in heart rate variability during sleep in women: the study of
      women across the nation sleep study.
AB  - BACKGROUND: Heart rate variability (HRV) differs markedly by race, yet few
      studies have evaluated these relationships in women, and none have done so during
      sleep (sHRV). METHODS: We addressed these gaps by examining sHRV in women of
      African American, Chinese American, or European American origin or descent (mean
      [standard deviation] age = 51.2 [2.2] years). RESULTS: HRV during Stage 2 non
      rapid eye movement (NREM) and rapid eye movement (REM) sleep differed
      significantly by race after adjusting for possible confounders. Normalized high
      frequency HRV was significantly lower in European American compared with African
      American and Chinese American participants (European American NREM = 0.35 [0.01],
      REM = 0.23 [0.01]; African American NREM = 0.43 [0.02], REM = 0.29 [0.02];
      Chinese American NREM = 0.47 [0.03], REM = 0.33 [0.02]; p values <.001). European
      Americans also exhibited higher low-to-high-frequency HRV ratios during sleep
      compared with African American and Chinese American women (European American NREM
      = 2.42 [1.07], REM = 5.05 [1.07]; African American NREM = 1.69 [1.09], REM = 3.51
      [1.09]; Chinese American NREM = 1.35 [1.07], REM = 2.88 [1.13]; p values <.001).
      CONCLUSIONS: Race was robustly related to sHRV. Compared with women of African
      American or Chinese American origin or descent, European American women exhibited
      decreased vagally mediated control of the heart during sleep. Prospective data
      are needed to evaluate whether sHRV, including race differences, predicts
      cardiovascular disease.

PMID- 24077774
TI  - Going, going, gone? Proactive control prevents the congruency   sequence effect
      from rapid decay.
AB  - The congruency sequence effect, the finding of a reduced congruency effect
      following incongruent trials in conflict tasks, has received considerable
      attention in the research on cognitive control over the last two decades. This
      effect can reflect either the expectancy-guided, preparatory biasing of attention
      in anticipation of the upcoming stimulus (i.e. proactive control), or the phasic
      enhancement of the attentional set in response to conflict on the previous trial
      (i.e. reactive control). A recent study by Egner et al. in Front Psychol 1 (2010)
      set out to contrast these two alternatives, by exploring the congruency sequence
      effect across a wide range of inter-trial intervals. It was found that congruency
      sequence effects were subject to rapid decay over time. This decay fits well with
      the notion of reactive control, while at the same time speaking against the
      involvement of proactive regulation-which should also (and even mainly) be
      evident at longer intervals. In the present study, we first replicate the
      reduction of the congruency sequence effect with increasing inter-trial interval
      in a face-word Stroop task. In a second experiment, we show that congruency
      sequence effects are observed at longer intervals, too, when the proportion of
      trials with the longest inter-trial interval is increased. Our findings indicate
      that proactive control can prevent the congruency sequence effect from decaying
      rapidly.

PMID- 24077775
TI  - Vertical metaphor with motion and judgment: a valenced  congruency effect with
      fluency.
AB  - Following metaphorical theories of affect, several research studies have shown
      that the spatial cues along a vertical dimension are useful in qualifying
      emotional experience (HAPPINESS is UP, SADNESS is DOWN). Three experiments were
      conducted to examine the role of vertical motion in affective judgment. They
      showed that positive stimuli moving UPWARD were evaluated more positively than
      those moving DOWNWARD, whereas negative stimuli moving DOWNWARD were evaluated as
      less negative than those moving UPWARD. They showed a valenced congruency effect,
      but an alternative hypothesis in terms of MORE is UP and LESS is DOWN was also
      examined. Finally, fluency mechanisms were investigated to confirm that
      relationships between affect and verticality were in accordance with a valenced
      congruency effect.

PMID- 24077776
TI  - Worrying and rumination are both associated with reduced  cognitive control.
AB  - Persistent negative thought is a hallmark feature of both major depressive
      disorder and generalized anxiety disorder. Despite its clinical significance,
      little is known about the underlying mechanisms of persistent negative thought.
      Recent studies suggest that reduced cognitive control might be an explanatory
      factor. We investigated the association between persistent negative thought and
      switching between internal representations in working memory, using the internal
      shift task (IST). The IST was administered to a group of undergraduates,
      classified as high-ruminators versus low-ruminators, or high-worriers versus low
      worriers. Results showed that high-ruminators and high-worriers have more
      difficulties to switch between internal representations in working memory as
      opposed to low-ruminators and low-worriers. Importantly, results were only
      significant when the negative stimuli used in the IST reflected personally
      relevant worry themes for the participants. The results of this study indicate
      that rumination and worrying are both associated with reduced cognitive control
      for verbal information that is personally relevant.

PMID- 24077777
TI  - The European "year of the air": fact, fake or vision?

PMID- 24077778
TI  - Letter to the editor: surgical treatment of vertically unstable lateral clavicle
      fractures (Neer 2b) with locked plate fixation and coracoclavicular ligament
      reconstruction.

PMID- 24077779
TI  - Clinical and radiographical results after double flip button stabilization of
      acute grade III and IV acromioclavicular joint separations.
AB  - INTRODUCTION: Persistent horizontal instability after acute acromioclavicular
      (AC) joint separation may provoke unsatisfactory results of conservative
      treatment. HYPOTHESIS: the arthroscopically assisted double flip button
      stabilization of acute horizontally unstable grade III and IV AC joint
      disruptions results in full functional restoration and stable radiological
      reposition. MATERIALS: 21 patients treated for an acute grade III or IV AC joint
      separation were enrolled. Clinical assessment at least 2-year postoperative
      included the constant score (CS) and the simple shoulder test. A panorama stress
      view, bilateral axial view and an AC view were obtained for radiographic
      evaluation. RESULTS: 19 individuals (mean 37 years; 17 men) with 16 Rockwood type
      III and 3 type IV injuries were available for examination 24-51 months
      postoperatively. The mean CS was 90.2 points (SD 6.5) with no statistically
      significant difference between CS and age-adjusted normative values. The mean
      Simple Shoulder Test scored 11.5 points (range 8-12). Loss of reduction of more
      than 2 mm in the coronal plane stress views was present in 6 patients (32 %) with
      no associated loss of functional outcome. Two of four reported complications in
      four patients were treated surgically (one open revision with graft augmentation
      for coracoid implant break out, one arthroscopic capsular release for persistent
      glenohumeral stiffness). CONCLUSION: Arthroscopically assisted double flip button
      stabilization for acute grade III and IV AC joint separation restores fully
      horizontal stability and age-expected shoulder function, resulting in high
      patient satisfaction, despite a loss of reduction observed radiographically in
      approximately one-third of patients. LEVEL OF EVIDENCE: IV.

PMID- 24077780
TI  - Is hospital volume associated with length of stay, re-admissions and reoperations
      for total hip replacement? A population-based register analysis of 78 hospitals
      and 54,505 replacements.
AB  - INTRODUCTION: Hospital volume has been suggested to be a significant determinant
      of the outcome of joint replacement surgery. We updated previously published data
      on the effect of hospital volume on length of stay, re-admissions, and
      reoperations for total hip replacement (THR) at the population level in Finland.
      MATERIALS AND METHODS: A total of 54,505 THRs for primary osteoarthritis
      performed between 1998 and 2010 were identified from the Hospital Discharge
      Register and the Finnish Arthroplasty Register. Hospitals were classified into
      four groups according to the number of primary and revision total hip and knee
      arthroplasties performed on an annual basis over the whole study period: 1-199
      (group 1), 200-499 (group 2), 500-899 (group 3), and >900 (group 4). We analyzed
      the association between hospital procedure volume and length of stay (LOS),
      length of uninterrupted institutional care (LUIC), re-admissions and
      reoperations. RESULTS: The larger the volume group, the shorter were LOS and LUIC
      (p < 0.01). According to the adjusted data, risk for re-admission in 42 days was
      greater in group 1 than in group 4 (OR = 1.14; 95 % CI: 1.05-1.23). There was no
      difference in the risk for reoperation. CONCLUSION: LOS and LUIC ought to be
      shortened in lower volume hospitals.

PMID- 24077781
TI  - Immunoregulatory function of PIR-A/B+ DCs in the inflammatory responses of
      dextran sodium sulfate-induced colitis.
AB  - BACKGROUND: Dendritic cells (DCs) may play an important role in forms of
      inflammatory bowel disease (IBD), such as Crohn's disease and ulcerative colitis.
      DCs are generally recognized as initiators of acquired immunity and also serve as
      regulators of both innate and acquired immunity. We used the animal model of
      colitis induced by dextran sodium sulfate (DSS), and examined whether DCs
      prepared from the colon show immunoregulatory roles in the termination of DSS
      induced colitis. METHODS: C57BL/6 mice exposed to DSS for 5 days developed acute
      colitis. DCs were isolated from the large intestinal lamina propria, and then
      analyzed for phenotypical, functional, and genetic data. RESULTS: Only PIR
      A/B(low) conventional DCs (cDCs) were detected in the steady state. However,
      after the treatment of DSS, PIR-A/B(high) cDCs appeared and gradually increased
      from day 5 to day 7, at which time the DSS-induced colitis was terminated. Then,
      allogeneic mixed leukocyte reaction (MLR) was performed. The stimulatory activity
      of PIR-A/B(high) cDCs obtained on day 7 was very low, and the addition of PIR
      A/B(high) cDCs suppressed the T cell proliferation in MLR, indicating the
      immunoregulatory role of PIR-A/B(high) cDCs. The immunoregulatory role of PIR
      A/B(high) cDCs was confirmed by the in vivo transfer experiment, showing their
      therapeutic effect on DSS-induced colitis. The message level of TGFbetai was
      significantly higher in PIR-A/B(high) cDCs, while that of IFN-gamma was highly
      upregulated in PIR-A/B(low) cDCs, being well in accordance with the fact that PIR
      A/B(high) cDCs showed a suppressive function against activated T cells.
      CONCLUSION: PIR-A/B(high) cDCs showed a suppressive function against activated T
      cells by producing inhibitory cytokines.

PMID- 24077782
TI  - Antiepileptic medications in autism spectrum disorder: a systematic review and
      meta-analysis.
AB  - Electroencephalogram-recorded epileptiform activity is common in children with
      autism spectrum disorder (ASD), even without clinical seizures. A systematic
      literature search identified 7 randomized, placebo-controlled trials of
      antiepileptic drugs (AEDs) in ASD (total n = 171), including three of valproate,
      and one each of lamotrigine, levetiracetam, and topiramate. Meta-analysis
      revealed no significant difference between medication and placebo in four studies
      targeting irritability/agitation and three studies investigating global
      improvement, although limitations include lack of power and different medications
      with diverse actions. Across all seven studies, there was no significant
      difference in discontinuation rate between two groups. AEDs do not appear to have
      a large effect size to treat behavioral symptoms in ASD, but further research is
      needed, particularly in the subgroup of patients with epileptiform abnormalities.

PMID- 24077783
TI  - Strategies for perceiving facial expressions in adults with autism spectrum
      disorder.
AB  - Rutherford and McIntosh (J Autism Dev Disord 37:187-196, 2007) demonstrated that
      individuals with autism spectrum disorder (ASD) are more tolerant than controls
      of exaggerated schematic facial expressions, suggesting that they may use an
      alternative strategy when processing emotional expressions. The current study was
      designed to test this finding using photographs of real people. In addition, two
      control tasks were added to eliminate alternative explanations. We replicated the
      findings of Rutherford and McIntosh (J Autism Dev Disord 37:187-196, 2007) and
      also demonstrated that adults with ASD do not show this tolerance when evaluating
      how realistic the expressions are. These results suggest adults with ASD employ a
      rule-based strategy to a greater extent than typical adults when processing
      facial expressions but not when processing other aspects of faces.

PMID- 24077784
TI  - Developing mirror self awareness in students with autism spectrum disorder.
AB  - A teaching methodology and curriculum was designed to develop and increase
      positive self-awareness in students diagnosed with autism spectrum disorders
      (ASD). Joint attention (JA) strategies were first utilized to directly teach
      students about reflected mirror images, and then subsequently, to indirectly
      teach students about their reflected image. Not only were Mirror Self Awareness
      Development (MSAD) JA activities initiated and preferred by students over non
      MSAD JA activities, they yielded a four step framework with which to measure
      increases in student selfawareness. While the focus of this study was to increase
      positive self-awareness in students with ASD, it may contribute to understanding
      the developmental stages of 'Self'.

PMID- 24077785
TI  - Periodontal intraligament injection as alternative to inferior alveolar nerve
      block--meta-analysis of the literature from 1979 to 2012.
AB  - OBJECTIVES: In a first meta-analysis, inferior alveolar nerve block (IANB) and
      periodontal intraligamentary injection anesthesia (ILA) were compared with focus
      on the failure rate of local anesthesia, pain during injection, additional
      injections, cardiovascular disturbances (CVD), and method-inherent differences
      (unwanted side effects, latency time, amount of anesthetic solution, duration of
      anesthesia) in adult patients. MATERIALS AND METHODS: Prospective and
      retrospective studies with clinical comparison of both injection techniques
      considering the relevant outcome parameters in adult patients from 1979 to 2012
      were included. A specific tool for assessing risk of bias in each included study
      was adopted. Data were assessed for methodological reliability and extracted and
      supplemented by sensitivity analysis by two independent reviewers. RESULTS: Seven
      studies were included [evidence grade Ib (n=1), IIb (n=3), and III (n=3)]. For
      other parameter than CVD, the significant heterogeneity of the random effects did
      not allow the reporting of pooled summary effect estimates. CVD were found
      significantly more often after IANB [odds ratio (OR): 0.12 (0.02-0.69)]. Further
      analysis revealed less injection pain in cases of ILA [OR: 0.32 (0.1-1)]. For
      failure rates as well as for needed additional injections, no significant
      differences were detected. IANB showed a latency of >3 min, whereas ILA had
      nearly none. The effect of IANB is longer than for ILA. CONCLUSIONS:
      Methodological and reporting flaws were consistently observed in the included
      articles. Except for CVD, it could not be shown that ILA is neither superior nor
      inferior compared to IANB. CLINICAL RELEVANCE: IANB as "gold standard" for
      routine dental treatments should be discussed.

PMID- 24077786
TI  - Improving the dose-myelotoxicity correlation in radiometabolic therapy of bone
      metastases with 153Sm-EDTMP.
AB  - PURPOSE: (153)Sm-ethylene diamine tetramethylene phosphonic acid ((153)Sm-EDTMP)
      is widely used to palliate pain from bone metastases, and is being studied for
      combination therapy beyond palliation. Conceptually, red marrow (RM) dosimetry
      allows myelotoxicity to be predicted, but the correlation is poor due to
      dosimetric uncertainty, individual sensitivity and biological effects from
      previous treatments. According to EANM guidelines, basic dosimetric procedures
      have been studied to improve the correlation between dosimetry and myelotoxicity
      in (153)Sm-EDTMP therapy. METHODS: RM dosimetry for 33 treatments of bone
      metastases from breast, prostate and lung tumours was performed prospectively
      (with (99m)Tc-MDP) and retrospectively, acquiring whole-body scans early and late
      after injection. The (153)Sm-EDTMP activity was calculated by prospective
      dosimetry based on measured skeletal uptake and full physical retention, with the
      RM absorbed dose not exceeding 3.8 Gy. Patient-specific RM mass was evaluated by
      scaling in terms of body weight (BW), lean body mass (LBM) and trabecular volume
      (TV) estimated from CT scans of the L2-L4 vertebrae. Correlations with toxicity
      were determined in a selected subgroup of 27 patients, in which a better
      correlation between dosimetry and myelotoxicity was expected. RESULTS: Skeletal
      uptakes of (99m)Tc and (153)Sm (Tc% and Sm%) were well correlated. The median Sm%
      was higher in prostate cancer (75.3 %) than in lung (60.5%, p = 0.005) or breast
      (60.8%, p = 0.008). PLT and WBC nadirs were not correlated with administered
      activity, but were weakly correlated with uncorrected RM absorbed doses, and the
      correlation improved after rescaling in terms of BW, LBM and TV. Most patients
      showed transient toxicity (grade 1-3), which completely and spontaneously
      recovered over a few days. Using TV, RM absorbed dose was in the range 2-5 Gy,
      with a median of 312 cGy for PLT in patients with toxicity and 247 cGy in those
      with no toxicity (p = 0.019), and 312 cGy for WBC in those with toxicity and 232
      cGy in those with no toxicity (p = 0.019). ROC curves confirmed the correlations,
      yielding toxicity absorbed dose thresholds of 265 cGy for PLT and 232 cGy for
      WBC. CONCLUSION: The best predictor of myelotoxicity and blood cells nadir was
      obtained scaling the RM absorbed dose in terms of the estimated TV. It seems
      clear that the increase in skeletal uptake due to the presence of bone metastases
      and the assumption of full physical retention cause an overestimation of the RM
      absorbed dose. Nevertheless, an improvement of the dose-toxicity correlation is
      easily achievable by simple methods, also leading to possible improvement in
      multifactorial analyses of myelotoxicity.

PMID- 24077787
TI  - Altered mental status in a teenager.

PMID- 24077788
TI  - Commentary.

PMID- 24077789
TI  - Commentary.

PMID- 24077790
TI  - Ulf-Hakan Stenman.

PMID- 24077791
TI  - A case of solid blood.

PMID- 24077795
TI  - An artist who vastly enriched medical education: Frank H. Netter.

PMID- 24077796
TI  - Direct cerebral and cardiac 17O-MRI at 3 Tesla: initial results at natural
      abundance.
AB  - PURPOSE: To establish direct (17)O-magnetic resonance imaging (MRI) for metabolic
      imaging at a clinical field strength of 3 T. METHODS: An experimental setup
      including a surface coil and transmit/receive switch was constructed. Natural
      abundance in vivo brain images of a volunteer were acquired with a radial three
      dimensional (3D) sequence in the visual cortex and in the heart with
      electrocardiogram (ECG)-gating. RESULTS: In the brain, a signal-to-noise ratio of
      36 was found at a nominal resolution of (5.6 mm)(3), and a transverse relaxation
      time of T(2)* = (1.9 +/- 0.2) ms was obtained. In the heart (17)O images were
      acquired with a temporal resolution of 200 ms. CONCLUSION: Cerebral and cardiac
      (17)O-MRI at natural abundance is feasible at 3 T.

PMID- 24077797
TI  - Nitric oxide and Takotsubo syndrome: an "angle" in need of exploration and
      exploitation.

PMID- 24077798
TI  - In vivo selection of tumor-specific antibodies.

PMID- 24077801
TI  - Correlation of reduction and clinical outcome in patients with degenerative
      spondylolisthesis.
AB  - STUDY DESIGN: Prospective cohort study. INTRODUCTION: Operative treatment is
      increasingly implemented for the treatment of degenerative lumbar listhesis, with
      lumbar fusion the most common intervention. Prediction of clinical outcomes after
      such procedures is of ongoing relevance, and the correlation of radiologic
      parameters with clinical outcome remains controversial. In particular, clinical
      studies have not determined conclusively whether reduction of slipped vertebrae
      is beneficial. METHODS: We performed a monocenter prospective analysis of a
      comprehensive set of quality of life scores (QLS) (Core Outcome Measure Index,
      Oswestry Low Back Pain Disability Index, SF-36) of 40 patients, who underwent a
      standardized PLIF procedure for symptomatic, Spondylolisthesis. Follow-up was 24
      months. The correlations between the radiologic parameters (degree of slippage,
      sagittal rotation) and the clinical scores before surgery as well as 12 and 24
      months post-operatively were examined. RESULTS: All QLS showed a statistically
      significant improvement after 12 and 24 months post-operatively (p < 0.05). The
      mean amount of the anterior slippage was 34.2 +/- 14.7 % (minimum 12 %, maximum
      78 %). After 12 months, there was an average 19.1 % decrease to 15.1 +/- 8.3 %
      (minimum 2 %, maximum 38 %, p < 0.000) and after 24 months it was decreased by
      18.0-16.2 +/- 9.0 % (minimum 2.9 %, maximum 40 %, p < 0.000). Average sagittal
      rotation measured 67.3 degrees  +/- 16.6 degrees  initially (minimum 35 degrees ,
      maximum 118) and decreased by 4.3 degrees  to an average of 63.0 degrees  +/-
      15.2 degrees  at 12 months post-surgery (minimum 15 degrees , maximum 101 degrees
      , p = 0.065,), and by 5.7 degrees  to an average of 61.6 degrees  +/- 13.0
      degrees  at 24 months (minimum 15 degrees , maximum 90 degrees , p = 0.044). The
      data show positive correlations between the amount of reduction of the slipped
      vertebra as well as the amount of correction of the sagittal rotation and the
      improvement of the clinical outcomes(r = 0.31-0.54, p < 0.05). CONCLUSION: The
      current study indicates a modest advantage for the best possible reposition in
      respect of the clinical outcome.

PMID- 24077802
TI  - Volunteerism or Labor Exploitation? Harnessing the Volunteer Spirit to Sustain
      AIDS Treatment Programs in Urban Ethiopia.
AB  - Based on ethnographic research in Addis Ababa, Ethiopia, this paper describes NGO
      efforts to encourage AIDS care volunteers to eschew material returns for their
      labor and instead reflect on the goodness of sacrificing to promote the survival
      of people living with HIV/AIDS. Consensus analysis of motivational survey data
      collected from a sample of AIDS care volunteers (n=110) suggests that they
      strongly share a sacrificial and prosocial motivational model. These results may
      be explained by several factors, including the efforts of the organizations to
      shape volunteers' motivations, the self-selection of volunteers, positive
      reinforcement in seeing one's patients become healthy, and social desirability
      bias. In-depth interviews examining the motivations and behaviors of volunteers
      reveal a more complicated picture: even ostensibly devoted and altruistic
      volunteers strongly question their service commitments. The complexity and
      ambivalence of volunteers' motivations reflect the profound uncertainty that they
      face in achieving improved socioeconomic status for themselves and their families
      amid widespread unemployment and sharply rising food prices. Their desires for
      economic opportunities explain why local NGOs exert so much effort to shape and
      sustain-and yet fail to completely control-their motivations. This recasts
      economically-insecure volunteers' consent to donate their labor as a process of
      negotiation with their organizers. Future research should explore how models of
      health care volunteerism and volunteer motivations are shaped by individual and
      collective experiences in political-economic context.

PMID- 24077803
TI  - Competition and interplay between the lithium bonding and hydrogen bonding:
      R3C...HY...LiY and R3C...LiY...HY triads as a working model (R=H, CH3; Y=CN, NC).
AB  - UMP2 calculations with aug-cc-pVDZ basis set were used to analyze intermolecular
      interactions in R3C...HY...LiY and R3C...LiY...HY triads (R=H, CH3; Y=CN, NC),
      which are connected via lithium and hydrogen bonds. To better understand the
      properties of these systems, the corresponding dyads were also studied. Molecular
      geometries and binding energies of dyads, and triads were investigated at the
      UMP2/aug-cc-pVDZ computational level. Particular attention was paid to parameters
      such as cooperative energies, and many-body interaction energies. All studied
      complexes, with the simultaneous presence of a lithium bond and a hydrogen bond,
      showed cooperativity with energy values ranging between -1.71 and -9.03 kJ mol-1.
      The electronic properties of the complexes were analyzed using parameters derived
      from atoms in molecules (AIM) methodology. Energy decomposition analysis revealed
      that the electrostatic interactions are the major source of the attraction in the
      title complexes.

PMID- 24077804
TI  - Effects of repeated treatment with the dopamine D2/D3 receptor partial agonist
      aripiprazole on striatal D2/D3 receptor availability in monkeys.
AB  - RATIONALE: Chronic treatment with dopamine (DA) receptor agonists and antagonists
      can differentially affect measures of DA D2/D3 receptor number and function, but
      the effects of chronic treatment with a partial D2/D3 receptor agonist are not
      clear. OBJECTIVE: We used a within-subjects design in male cynomolgus monkeys to
      determine the effects of repeated (17-day) treatment with the D2/D3 receptor
      partial agonist aripiprazole (ARI; 0.03 mg/kg and 0.1 mg/kg i.m.) on food
      reinforced behavior (n = 5) and on D2/D3 receptor availability as measured with
      positron emission tomography (PET; n = 9). METHODS: Five monkeys responded under
      a fixed-ratio 50 schedule of food reinforcement and D2/D3 receptor availability
      was measured before and 4 days after ARI treatment using PET and the D2/D3
      receptor-selective radioligand [18F]fluoroclebopride (FCP). Four additional
      monkeys were studied using [11C]raclopride and treated sequentially with each
      dose of ARI for 17 days. RESULTS: ARI decreased food-maintained responding with
      minimal evidence of tolerance. Repeated ARI administration increased FCP and
      raclopride distribution volume ratios (DVRs) in the caudate nucleus and putamen
      in most monkeys, but decreases were observed in monkeys with the highest baseline
      DVRs. CONCLUSIONS: The results indicate that repeated treatment with a low
      efficacy DA receptor partial agonist produces effects on brain D2/D3 receptor
      availability that are qualitatively different from those of both high-efficacy
      receptor agonists and antagonists, and suggest that the observed individual
      differences in response to ARI treatment may reflect its partial agonist
      activity.

PMID- 24077805
TI  - 5-azacytidine reduces methylation, promotes differentiation and induces tumor
      regression in a patient-derived IDH1 mutant glioma xenograft.
AB  - Somatic mutations in Isocitrate Dehydrogenase 1 (IDH1) are frequent in low grade
      and progressive gliomas and are characterized by the production of 2
      hydroxyglutarate (2-HG) from alpha-ketoglutarate by the mutant enzyme. 2-HG is an
      "oncometabolite" that competitively inhibits alpha-KG dependent dioxygenases
      resulting in various widespread cellular changes including abnormal
      hypermethylation of genomic DNA and suppression of cellular differentiation.
      Despite the growing understanding of IDH mutant gliomas, the development of
      effective therapies has proved challenging in part due to the scarcity of
      endogenous mutant in vivo models. Here we report the generation of an endogenous
      IDH1 anaplastic astrocytoma model which rapidly grows in vivo, produces 2-HG and
      exhibits DNA hypermethylation. Using this model, we have demonstrated the
      preclinical efficacy and mechanism of action of the FDA approved demethylating
      drug 5-azacytidine in vivo. Long term administration of 5-azacytidine resulted in
      reduction of DNA methylation of promoter loci, induction of glial
      differentiation, reduction of cell proliferation and a significant reduction in
      tumor growth. Tumor regression was observed at 14 weeks and subsequently showed
      no signs of re-growth at 7 weeks despite discontinuation of therapy. These
      results have implications for clinical trials of demethylating agents for
      patients with IDH mutated gliomas. 

PMID- 24077806
TI  - Dopamine- and zinc-induced autophagosome formation facilitates PC12 cell
      survival.
AB  - Dopamine oxidation and divalent cations have been reported to induce neuronal
      cell death. Although autophagy is involved in neuronal cell death, it has also
      been suggested to facilitate cell survival. We sought to investigate the role of
      autophagy in PC12 cells and cultured neurons treated with dopamine and Zn2+.
      Cells expressing EGFP-LC3 were treated with high concentrations of dopamine and
      Zn2+, and the formation of EGFP-LC3 fluorescence aggregates was monitored. Our
      results showed a significant increase in the number of fluorescent puncta in the
      cytosol of PC12 cells treated with these chemicals. These treatments enhanced LC3
      lipidation levels in PC12 cells. Decreasing the ATG7 protein level using specific
      small interference RNA (siRNA) and pretreating with phosphatidylinositol 3
      phosphate kinase blockers, wortmannin and LY294002, inhibited puncta formation.
      Dopamine or Zn2+ treatment significantly elevated the intracellular Zn2+
      concentration ([Zn2+] i ); however, inhibiting the [Zn2+] i elevation in dopamine
      treated cells suppressed the puncta formation. LY294002 or siRNA-directed members
      of the autophagy pathway increased the fraction of phosphatidylserine present on
      the outer membrane leaflet in PC12 cells treated with dopamine or Zn2+,
      suggesting an increase in apoptosis. Primary embryonic midbrain neurons
      expressing EGFP-LC3 also displayed a significant increase in the number of
      fluorescent aggregates in cells upon treatment with dopamine or Zn2+. Dopamine or
      Zn2+ treatment significantly elevated the [Zn2+] i in neurons and caused neuronal
      death. Our results indicate that treating cells with dopamine and Zn2+ results in
      the activation of the autophagy pathway in an effort to enhance cell survival.

PMID- 24077807
TI  - FK506 affects mitochondrial protein synthesis and oxygen consumption in human
      cells.
AB  - FK506 is an important immunosuppressive medication. However, it can provoke
      neurotoxicity, nephrotoxicity, and diabetes as adverse side effects. The decrease
      in oxygen consumption of rat cells treated with pharmacologically relevant
      concentrations of FK506, along with other evidences, has insinuated that some of
      the toxic effects are probably caused by drug-induced mitochondrial dysfunction
      at the level of gene expression. To confirm this suggestion, we have analyzed
      cell respiration and mitochondrial protein synthesis in human cell lines treated
      with FK506. This drug provokes an important decrease in oxygen consumption,
      accompanied by a slight reduction in the synthesis of mitochondria DNA-encoded
      proteins. These results are similar to those triggered by rapamycin, another
      macrolide with immunosuppressive properties, therefore insinuating a common toxic
      pathway.

PMID- 24077808
TI  - Computational Modeling of Human Paraoxonase 1: Preparation of Protein Models,
      Binding Studies, and Mechanistic Insights.
AB  - The enzyme human paraoxonase 1 (huPON1) has demonstrated significant potential
      for use as a bioscavenger for treatment of exposure to organophosphorus (OP)
      nerve agents. Herein we report the development of protein models for the human
      isoform derived from a crystal structure of a chimeric version of the protein
      (pdb ID: 1V04) and a homology model derived from the related enzyme
      diisopropylfluorophosphatase (pdb ID: 1XHR). From these structural models,
      binding modes for OP substrates are predicted, and these poses are found to
      orient substrates in proximity to residues known to modulate specificity of the
      enzyme. Predictions are made with regard to the role that residues play in
      altering substrate binding and turnover, in particular with regard to the
      stereoselectivity of the enzyme, and the known differences in activity related to
      a natural polymorphism in the enzyme. Potential mechanisms of action of the
      protein for catalytic hydrolysis of OP substrates are also evaluated in light of
      the proposed binding modes.

PMID- 24077809
TI  - Modeling of stem cell dynamics in human colonic crypts in silico.
AB  - BACKGROUND: Several possible scenarios of cellular dynamics in human colonic
      crypts have been inferred from transgenic animal experiments. However, because of
      the discrepancy in size and physiology between humans and animals, quantitative
      predictions of tissue renewal and cancer development are difficult to execute.
      METHODS: A two-dimensional individual based model was developed for the first
      time to predict cellular dynamics in human colonic crypts. A simple scenario, in
      which stem cells were not fixed positionally, divide symmetrically and
      asymmetrically in a stochastic fashion in the lower part of the crypt, was
      proposed and implemented in the developed model. Numerical simulations of the
      model were executed in silico. RESULTS: By comparing the results of computational
      simulations with available experimental data, the presented scenario was
      consistent with various experimental evidence. Using this scenario, we simulated
      and visualized monoclonal conversion in the human colonic crypt. We also
      predicted that the propensity for monoclonal expansion of a mutant cell was
      largely dependent on the phenotype, the cell type, the position and the state of
      the crypt. CONCLUSIONS: Using the computational framework developed in this
      study, model users can verify possible scenarios of stem cell dynamics occurring
      in human colonic crypts and quantitatively predict cell behavior. Its
      applicability in scenario verification and predictability makes it a valuable
      tool for elucidation of stem cell dynamics in human colonic crypts.

PMID- 24077811
TI  - Mucins in Gastric Cancer - An Update.
AB  - Mucins are high-molecular-weight glycoproteins expressed throughout the
      gastrointestinal tract, with a key role in mucosal protection and function. In
      gastric cancer expression of MUC5AC and MUC1 is reduced and denovo expression of
      MUC2 occurs. With progressive loss of tumor differentiation and increased tumor
      stage, expression of MUC5AC and MUC1 is further reduced, and MUC2 decreases.
      Isolated MUC2 expression (the intestinal phenotype) correlates with metastatic
      spread and poor survival. There is emerging evidence that MUC1 acts as an
      oncoprotein when overexpressed. The cytoplasmic tail of MUC1 interacts with the
      H. pylori virulence factor cagA and is a major effector of the wnt-beta catenin
      intracellular signalling cascade. Polymorphism in the MUC1 gene has been
      identified in gastric cancer patients and may have a prospective role in the
      stratification of high-risk subjects. The MUC1 gene also mediates resistance to
      the recombinant HER2/neu antibody trastuzumab. Future research efforts will
      examine targeting MUC1 for therapeutic purposes.

PMID- 24077810
TI  - Connections between preimplantation embryo physiology and culture.
AB  - PURPOSE: To review the history of experimental embryo culture and how culture
      media that permitted complete preimplantation development in vitro were first
      discovered, and the physiological insights gained. METHODS: This article reviews
      the history of in vitro mammalian embryo culture, in particular the efforts that
      led to the current generation of successful culture media and how these reflect
      embryo physiology, highlighting the contributions of Dr. John D. Biggers and his
      colleagues and students. RESULTS: The culture of mammalian embryos began about a
      century ago. However, defined media without biological fluids were only developed
      in the late 1950s, and the first live young born from cultured embryos, using
      these media, were produced by McLaren and Biggers in 1958. It wasn't until the
      late 1980s, however, that preimplantation mammalian embryos could generally be
      cultured in vitro from fertilized eggs to blastocysts. These new media led to
      insights into embryo physiology, including the importance of cell volume
      homeostasis to early embryo viability. CONCLUSIONS: The development of successful
      preimplantation embryo culture media has had a profound effect on assisted
      reproduction technologies and on research into early embryo physiology.

PMID- 24077812
TI  - Five-year postoperative outcomes of apodized diffractive multifocal intraocular
      lens implantation.
AB  - PURPOSE: To assess the long-term postoperative visual performance of an apodized
      diffractive multifocal intraocular lens (IOL). METHODS: Twenty-one patients (42
      eyes) underwent cataract surgery with bilateral implantation of an apodized
      diffractive multifocal IOL. The monocular uncorrected and corrected distance
      visual acuities, uncorrected, distance-corrected and corrected near visual
      acuities, and manifest refractive spherical equivalent were measured 1 and 5
      years postoperatively. The contrast sensitivity, incidence of glare or halos, and
      rate of neodynium:YAG (Nd:YAG) posterior capsulotomy were evaluated 5 years
      postoperatively. RESULTS: No significant differences were found between the
      distance and near visual acuities at 1 and 5 years postoperatively. The contrast
      sensitivity was within the normal range for all spatial frequencies. No patients
      reported severe glare or halos. Six (14.3 %) eyes required Nd:YAG posterior
      capsulotomy. CONCLUSIONS: The apodized diffractive multifocal IOL provides good,
      stable distance and near visual acuity levels over a 5-year follow-up period.

PMID- 24077813
TI  - Stem cell therapy for stress urinary incontinence: a systematic  review in human
      subjects.
AB  - PURPOSE: To systematically evaluate the current evidence on the safety and
      efficacy of stem cell therapy (SCT) in stress urinary incontinence (SUI) to allow
      objective comparison with existing surgical techniques. METHODS: Systematic
      literature search of Medline from years 1946-2012 using terms: "stem", "cell",
      "stress", "urinary", and "incontinence". Included studies presented empirical
      data on the treatment of SUI using SCT. OUTCOMES: adverse events, incontinence,
      quality of life, urodynamic, transurethral ultrasound and urethral EMG findings.
      RESULTS: Eight studies met inclusion criteria (seven observational and one
      randomized). Quality score: median 10.75 of 20 (range 2-12.5). Adverse events:
      one patient had bladder perforation and two procedures could not be completed due
      to pain. Temporary urinary retention and cystitis were also reported.
      Incontinence score: Four studies describe significant improvement. Quality of
      life: significant improvement in four studies. Urodynamic outcomes: four studies
      show significant improvement in contractility of urethral sphincter; three
      studies demonstrate no change in bladder capacity and significant reduction in
      residual volume; significant improvement in urinary flow three studies, although
      two found no difference; increase in leak point pressure and detrusor pressure in
      three studies. Urethral ultrasound: three studies found significant increases in
      rhabdosphincter thickness and contractility. Urethral EMG: two studies found
      significant increases in the EMG at rest and at contraction. CONCLUSION: Data
      suggest that SC treatment for SUI is safe and effective in the short term.
      However, the quality and maturity of the data are limited. Robust data from
      better quality studies comparing this to current surgical techniques are needed.

PMID- 24077814
TI  - A girl with labium majus swelling.
AB  - Asymmetric vulva swelling during prepubertal period is related to a variety of
      inflammatory and neoplastic lesions. An 11-year-old girl with childhood
      asymmetric labium majus enlargement is presented.

PMID- 24077815
TI  - Staging, surveillance, and evaluation of response to therapy in renal cell
      carcinoma: role of MDCT.
AB  - Renal cell carcinoma is the most common malignant renal tumor in the adults.
      Significant advances have been made in the management of localized and advanced
      renal cell carcinoma. Surgery is the standard of care and accurate pre-operative
      staging based on imaging is critical in guiding appropriate patient management.
      Besides staging, imaging plays a key role in the post-operative surveillance and
      evaluation of response to systemic therapies. Both CT and MR are useful in the
      staging and follow up of renal cell carcinoma, but CT is more commonly used due
      to its lower costs and wider availability. In this article, we discuss and
      illustrate the role of multi-detector CT in pre-operative staging, post-operative
      surveillance, and evaluation of response to systemic therapy in renal cell
      carcinoma.

PMID- 24077825
TI  - A catalyst for change in reproductive science: John D. Biggers as a mentor's
      mentor.

PMID- 24077826
TI  - Efficient induction of differentiation and growth inhibition in IDH1 mutant
      glioma cells by the DNMT Inhibitor Decitabine.
AB  - Mutation in the IDH1 or IDH2 genes occurs frequently in gliomas and other human
      malignancies. In intermediate grade gliomas, IDH1 mutation is found in over 70%
      of tumors. These mutations impart the mutant IDH enzyme with a neomorphic
      activity - the ability to synthesize 2-hydroxyglutarate (2-HG). This ability
      leads to a reprogramming of chromatin state, a block in differentiation, and the
      establishment of the glioma hypermethylator phenotype (G-CIMP). It has been
      hypothesized but not proven that the extensive DNA methylation that occurs in G
      CIMP tumors helps maintain and "lock in" glioma cancer cells in a
      dedifferentiated state. Here, we tested this hypothesis by treating patient
      derived IDH1 mutant glioma initiating cells (GIC) with non-cytotoxic,
      epigenetically targeted doses of the DNMT inhibitor decitabine. Global methylome
      analysis of treated IDH1 mutant GICs showed that DAC treatment resulted in
      reversal of DNA methylation marks induced by IDH and the re-expression of genes
      associated with differentiation. Accordingly, treatment of IDH1 mutant glioma
      cells resulted in a dramatic loss of stem-like properties and efficient adoption
      of markers of differentiation, effects not seen in decitabine treated IDH wild
      type GICs. Induction of differentiation was much more efficient than that seen
      following treatment with a specific inhibitor of mutant IDH enzyme (Agios).
      Decitabine also decreased replicative potential and tumor growth in vivo.
      Reexpression of polycomb regulated genes accompanied these DAC-induced
      phenotypes. In total, our data indicates that targeting the pathologic DNA
      methylation in IDH mutant cells can reverse mutant IDH induced hypermethylation
      and block in differentiation and promote tumor control. These findings have
      substantial impact for exploring new treatment strategies for patients with IDH
      mutant gliomas. 

PMID- 24077827
TI  - Maternal educational level and blood pressure, aortic stiffness, cardiovascular
      structure and functioning in childhood: the generation R study.
AB  - BACKGROUND: In adults, low level of education was shown to be associated with
      higher blood pressure levels and alterations in cardiac structures and function.
      It is currently unknown whether socioeconomic inequalities in arterial and
      cardiac alterations originate in childhood. Therefore, we investigated the
      association of maternal education with blood pressure levels, arterial stiffness,
      and cardiac structures and function at the age of 6 years and potential
      underlying factors. METHODS: The study included 5,843 children participating in a
      prospective cohort study in the Netherlands. Maternal education was assessed at
      enrollment. Blood pressure, carotid-femoral pulse wave velocity, left atrial
      diameter, aortic root diameter, left ventricular mass, and fractional shortening
      were measured at the age of 6 years. RESULTS: Children with low educated
      (category 1) mothers had higher systolic (2.80mm Hg; 95% confidence interval (CI)
      = 1.62-2.94) and diastolic (1.80mm Hg; 95% CI = 1.25-2.35) blood pressure levels
      compared with children with high educated (category 4) mothers. The main
      explanatory factors were the child's body mass index (BMI), maternal BMI, and
      physical activity. Maternal education was negatively associated with fractional
      shortening (P trend = 0.008), to which blood pressure and child's BMI contributed
      the most. No socioeconomic gradient was observed in other arterial and cardiac
      measurements. CONCLUSIONS: Socioeconomic inequalities in blood pressure are
      already present in childhood. Higher fractional shortening among children from
      low socioeconomic families might be a first cardiac adaptation to higher blood
      pressure and higher BMI. Interventions should be aimed at lowering child BMI and
      increasing physical activity among children from low socioeconomic families.

PMID- 24077828
TI  - Prevalence, awareness, treatment, and control rate of hypertension in HIV
      infected patients: the HIV-HY study.
AB  - BACKGROUND: We aimed to assess the prevalence of hypertension in an unselected
      human immunodeficiency virus (HIV)-infected population and to identify factors
      associated with hypertension prevalence, treatment, and control. METHODS: We used
      a multicenter, cross-sectional, nationwide study that sampled 1,182 unselected,
      consecutive, HIV-infected patients. Office blood pressure was accurately measured
      with standard procedures. RESULTS: Patients were 71% men and 92% white, with a
      median age of 47 years (range = 18-78); 6% were antiretroviral treatment naive.
      The overall prevalence of hypertension was 29.3%; high-normal pressure accounted
      for an additional 12.3%. Among hypertensive subjects, 64.9% were aware of their
      hypertensive condition, 52.9% were treated, and 33.0% were controlled (blood
      pressure < 140/90 mm Hg). Blood pressure-lowering medications were used in
      monotherapy in 54.3% of the subjects. Angiotensin-converting enzyme inhibitors
      and angiotensin receptor blockers were the most frequently used drugs (76.1%:
      monotherapy = 39.1%, combination treatment = 37.0%). In multivariable regression
      models, hypertension was independently predicted by traditional risk factors,
      including age >=50 years, male sex, family history of cardiovascular disease,
      body mass index >=25 kg/m2, previous cardiovascular events, diabetes, central
      obesity, and metabolic syndrome, as well as by duration of HIV infection,
      duration of antiretroviral therapy, and nadir CD4+ T-cell count <200/MUl. The
      choice of protease inhibitors vs. nonnucleoside reverse transcriptase inhibitors
      as a third antiretroviral drug was irrelevant. CONCLUSIONS: Hypertension affects
      nearly 30% of HIV adult outpatients in Italy. More than one-third of the
      hypertensive subjects are unaware of their condition, and more than two-thirds
      are uncontrolled. A higher level of attention to the diagnosis and treatment of
      hypertension is mandatory in this setting.

PMID- 24077829
TI  - Effect of mobile phase on resolution of the isomers and homologues of tocopherols
      on a triacontyl stationary phase.
AB  - Reversed-phase liquid chromatographic (RPLC) separation of isomers and homologues
      of similar polarity is challenging. Tocopherol isomers and homologues are one
      such example. alpha, beta, gamma, and delta-tocopherols have been successfully
      separated by RPLC on triacontyl (C30) stationary phase. System suitability was
      tested by using four mobile phases, and observed chromatographic separations of
      beta and gamma-tocopherols were compared. Comparison indicated that methanol-tert
      butyl methyl ether (TBME) 95:5 (v/v) at a flow rate of 0.75 mL min(-1) was the
      best mobile phase. Detection systems were also evaluated on the basis of limit of
      quantification; it was concluded that fluorescence detection was best. The method
      was validated by analysis of two homologues and two isomers of tocopherol in
      sesame, maize, and soybean samples. MS coupled with an ESI interface in negative
      ion mode [M - H](-) was used for identification of individual components. It was
      concluded that addition of TBME to methanol was required to enhance the
      separation of beta and gamma-tocopherols, although methanol alone provided
      similar results. The applicability of the method to cereal, pulse, and oilseed
      samples was confirmed. The reproducibility of the procedure was good, with
      relative standard deviations in the range 1.7-3.9%. Recovery of tocopherols added
      to sesame samples ranged from 91 to 99%.

PMID- 24077830
TI  - Circulating miRNAs: a new generation of anti-doping biomarkers.
AB  - MicroRNAs (miRNAs) are small non-coding RNAs that regulate a variety of
      biological processes. Cell-free miRNAs detected in blood plasma are used as
      specific and sensitive markers of physiological processes and some diseases.
      Circulating miRNAs are highly stable in body fluids, for example plasma.
      Therefore, profiles of circulating miRNAs have been investigated for potential
      use as novel, non-invasive anti-doping biomarkers. This review describes the
      biological mechanisms underlying the variation of circulating miRNAs, revealing
      that they have great potential as a new class of biomarker for detection of
      doping substances. The latest developments in extraction and profiling
      technology, and the technical design of experiments useful for anti-doping, are
      also discussed. Longitudinal measurements of circulating miRNAs in the context of
      the athlete biological passport are proposed as an efficient strategy for the use
      of these new markers. The review also emphasizes potential challenges for the
      translation of circulating miRNAs from research into practical anti-doping
      applications.

PMID- 24077831
TI  - Identification of volatiles from oxidised phosphatidylcholine molecular species
      using headspace solid-phase microextraction (HS-SPME) and gas chromatography-mass
      spectrometry (GC-MS).
AB  - Headspace solid-phase microextraction (HS-SPME) followed by gas chromatography
      mass spectrometry analysis (GC-MS) was used to investigate the volatile compounds
      from oxidised phosphatidylcholine molecular species. 1-stearoyl-2-oleoyl-sn
      glycero-3-phosphocholine (SOPC) and 1-stearoyl-2-linoleoyl-sn-glycero-3
      phosphocholine (SLPC) were chosen as models. The influence of several parameters
      on the efficiency of volatile oxidised compounds (VOCs) microextraction, such as
      type of fibre, extraction duration and temperature were studied. The best results
      were obtained with a polydimethylsiloxane/divinylbenzene (PDMS/DVB) fibre used at
      50  degrees C during 25 min. The effect of oxidation temperature on the yield of
      VOCs from SOPC and SLPC was investigated. Oxidative kinetics of SOPC and SLPC
      were investigated by measuring both the production of VOCs and the degradation of
      starting materials. More than 30 VOCs were detected by means of the reference
      mass spectra of the National Institute of Standards and Technology mass spectral
      library, and most of them were further confirmed by comparing their mass spectra
      and retention time with those obtained from authentic reference compounds under
      the same analytical conditions. Moreover, the origins of VOCs from oxidised PLs
      were studied by comparing those obtained from their corresponding
      triacylglycerides under the same experimental conditions. The main VOCs
      identified from oxidised SOPC were (E)-2-decenal, nonanal and octanal and from
      oxidised SLPC were (E)-2-heptenal, (E)-2-octenal and (E, E)-2,4-decadienal. The
      proposed method was applied to a real food sample, soy lecithin.

PMID- 24077832
TI  - Palatal perforation with McGrath Series 5 videolaryngoscope.

PMID- 24077833
TI  - Stroke volume-directed administration of hydroxyethyl starch   (HES 130/0.4) and
      Ringer's acetate in prone position   during neurosurgery: a randomized controlled
      trial.
AB  - PURPOSE: General anesthesia in the prone position is associated with hypotension.
      We studied stroke volume (SV)-directed administration of hydroxyethyl starch (HES
      130 kDa/0.4) and Ringer's acetate (RAC) in neurosurgical patients operated on in
      a prone position to determine the volumes required for stable hemodynamics and
      possible coagulatory effects. METHODS: Thirty elective neurosurgical patients
      received either HES (n = 15) or RAC (n = 15). Before positioning, SV measured by
      arterial pressure waveform analysis was maximized by fluid boluses until SV did
      not increase more than 10 %. SV was maintained by repeated administration of
      fluid. RAC 3 ml/kg/h was infused in both groups. Thromboelastometry assessed
      coagulation. Mann-Whitney U test, Wilcoxon signed-rank test, ANOVA on ranks, and
      a linear mixed model were applied. RESULTS: Comparable hemodynamics were achieved
      with the mean cumulative (SD) boluses of HES or RAC 240 (51) or 267 (62) ml (P =
      0.207) before positioning, 340 (124) or 453 (160) ml (P = 0.039) 30 min after
      positioning, and 440 (229) or 653 (368) ml at the end of surgery (P = 0.067). The
      mean dose of basal RAC infusion was 813 (235) and 868 (354) ml (P = 0.620) in the
      HES and RAC group, respectively. Formation and maximum strength of the fibrin
      clot were decreased in the HES group. Intraoperative blood loss was comparable
      between groups (P = 0.861). CONCLUSION: The amount of RAC needed in the prone
      position was 25 % greater. The cumulative dose of 440 ml HES induced a slight
      disturbance in fibrin formation and clot strength. We suggest cautious
      administration of HES during neurosurgery.

PMID- 24077834
TI  - Use of an emergency department in Saint-Laurent du Maroni, French guiana: does
      being undocumented make a difference?
AB  - Few data exist on the health status and heathcare utilization of the undocumented
      migrants in France. Data are particularly scarce in French overseas territories
      where this population is numerous. We aimed to describe the characteristics of
      undocumented patients who use the emergency department of Saint-Laurent du Maroni
      Hospital(SLMH) in French Guiana, and to identify factors associated with their
      subsequent hospitalization. In a random sample of 177 patients, we used logistic
      regression models to test the mediational role of health-care system utilization
      and medical characteristics at admission in the association between residency
      status and hospitalization.More than a quarter of patients (27.7 %) were
      undocumented migrants, who were subsequently hospitalized more often than the
      others [OR 3.11, 95 % CI (1.32-7.34)]. More-severe symptoms at admission, a
      poorer access to health insurance, a greater distance between their home and
      SLMH, and poorer French language skills partially explained this higher
      hospitalization rate. Despite the fact that France has instituted a specific
      insurance program for the undocumented, an increasing number of barriers to
      accessing health care is being reported for these people. Our results suggest
      that these obstacles have some impacts in the utilization of hospital care.

PMID- 24077836
TI  - Health Fair Report of Asian Americans in Michigan.
AB  - There is little information about Asian American health in Michigan. This
      highlights an urgent need to collect their health data to understand and help
      this fastest growing ethnic group live healthier lives and reduce health
      disparities. Data for about 300 individuals attending two major health fairs were
      collected to study older Chinese and Vietnamese immigrants. The analyses show
      that they have high prevalence rates of hypertension, high cholesterol and
      diabetes, even though their body mass index is relatively low. The report of
      these analyses is a starting point to understand the study groups. Such data can
      help health care providers give sound advice to their patients and allow those of
      us in public health to design proper health programs that may benefit them. But
      more data is needed to include major Asian ethnic groups and identify common
      health concerns among all Asian Americans.

PMID- 24077835
TI  - Discrimination and psychiatric disorder among Asian American immigrants: a
      national analysis by subgroups.
AB  - Although considerable evidence suggests that discrimination negatively affects
      mental health for Asian American (AA) immigrants, few studies have disaggregated
      this heterogeneous community and/or differentiated effects of different forms of
      discrimination. Using the first nationally representative data on AA immigrants
      in US, this study examines whether perceived racial discrimination, perceived
      language discrimination, and vicarious racism experiences increase the risk of
      psychiatric disorder for different Asian immigrant groups in the past 12 months.
      Results from group specific logistic regressions show that both perceived racial
      and language discrimination have strong deleterious effects on mental health only
      for Filipinos, while Vietnamese and Chinese are more likely to be affected by
      vicarious racism experiences. No significant association was found between racial
      discrimination and the mental health outcome for Vietnamese and Chinese. Findings
      were discussed in the light of inter-racial contact pattern and acculturation
      status for each group.

PMID- 24077837
TI  - Theoretical investigations on the synthesis mechanism of cyanuric acid from NH3
      and CO2.
AB  - In the synthesis of cyanuric acid from NH3 and CO2, urea and isocyanic acid OCNH
      are two pivotal intermediates. Based on density functional theory (DFT)
      calculations, the synthesis mechanism of cyanuric acid from NH3 + CO2 was
      investigated systematically. Urea can be synthesized from NH3 and CO2, and
      cyanuric acid can be obtained from urea or NH3 + CO2. In the stepwise mechanism
      of cyanuric acid from urea or NH3 + CO2, the energy barriers are relatively high,
      and the condition of high pressure and temperature does not decrease the energy
      barriers. Our theoretical model shows that cyanuric acid is actually acquired
      from OCNH via a one-step cycloaddition reaction.

PMID- 24077838
TI  - A theoretical investigation on the conformation and the interaction of
      CHF2OCF2CHF2 (desflurane II) with one water molecule.
AB  - The conformation and the interaction of CHF2OCF2CHF2 (desflurane II) with one
      water molecule is investigated theoretically using the ab initio MP2/aug-cc-pvdz
      and DFT-based M062X/6-311++G(d,p) methods. The calculations include the optimized
      geometries, the harmonic frequencies of relevant vibrational modes along with a
      natural bond orbital (NBO) analysis including the NBO charges, the hybridization
      of the C atom and the intra- and intermolecular hyperconjugation energies. In the
      two most stable conformers, the CH bond of the F2HCO- group occupies the gauche
      position. The hyperconjugation energies are about the same for both conformers
      and the conformational preference depends on the interaction between the non
      bonded F and H atoms. The deprotonation enthalpies of the CH bonds are about the
      same for both conformers, the proton affinity of the less stable conformer being
      3 kcal mol-1 higher. Both conformers of desflurane II interact with water forming
      cyclic complexes characterized by CH...O and OH...F hydrogen bonds. The binding
      energies are moderate, ranging from -2.4 to -3.2 kcal mol-1 at the MP2 level. The
      origin of the blue shifts of the nu(CH) vibrations is analyzed. In three of the
      complexes, the water molecule acts as an electron donor. Interestingly, in these
      cases a charge transfer is also directed to the non bonded OH group of the water
      molecule. This effect seems to be a property of polyfluorinated ethers.

PMID- 24077839
TI  - siRNA-participated chemotherapy: an efficient and specific therapeutic against
      gastric cancer.
AB  - PURPOSE: This study aims to investigate the role of siRNA silencing fibroblast
      growth factor receptor (FGFR) expression in promoting chemotherapy effect of
      gastric cancer and to explore its mechanism. METHODS: Human gastric cancer cells
      MGC80-3 were divided into four groups: control group, cisplatin group (2 MUg/L),
      cisplatin (2 MUg/L) + siRNA group and siRNA group. The expressions of FGFR in
      four groups were detected by immunofluorescence. The cell proliferation and
      apoptosis were detected by MTT assay and flow cytometry. The protein expression
      levels of vascular endothelial growth factor receptor (VEGFR), caspase-3 and Bax
      were detected by Western blot. Further, animal model of gastric cancer was
      established and divided into four groups as in vitro experiment. The expression
      of FGFR mRNA in tumor tissue was detected by the real-time fluorescence
      quantitative polymerase chain reaction. The size of tumor was measured to analyze
      the effects of treatment. Histopathological detections were performed by
      hematoxylin and eosin staining and immunohistochemistry. RESULTS: For in vitro
      experiment, significant decrease inFGFR expression, inhibition of proliferation
      and promotion of apoptosis were observed in siRNA-treated cells, so as cisplatin
      group. siRNA also resulted in the reduction of VEGFR and rise in apoptosis
      related protein (caspase-3). As for the experiment in vivo, siRNA also suppressed
      the expression of FGFR and enhanced tumor shrink. Furthermore, the co
      administration of siRNA and cisplatin revealed a more excellent antitumor effect
      than other therapies. CONCLUSIONS: siRNA can effectively suppress FGFR expression
      and cell proliferation, but promote apoptosis in vitro and also inhibit tumor
      growth and FGFR production in vivo. siRNA-participated chemotherapy may provide
      an efficient therapeutic approach to treat gastric cancer.

PMID- 24077840
TI  - Association between survivin -31G>C polymorphism and cancer risk: meta-analysis
      of 29 studies.
AB  - PURPOSE: A growing body of evidence has shown the possible relevance of survivin 
      31G>C (rs9904341) promoter polymorphism to the genetic susceptibility of cancer.
      Because of the lack of available conclusive data, we performed a meta-analysis of
      all relevant available studies to derive a more precise estimation of the
      relationship. METHODS: A comprehensive literature search of Medline electronic
      database was conducted to collect relevant studies until August 18, 2013.
      References of the retrieved articles were also screened. The extracted data were
      statistically analyzed, and pooled odds ratios (ORs) with 95 % confidence
      intervals (CIs) were calculated to estimate the association strength using Stata
      version 11.2 software. RESULTS: A total of 29 studies with 7,473 cancer cases and
      9,086 controls were included in the meta-analysis. Overall, the pooled analysis
      revealed that suvivin -31G>C polymorphism was significantly associated with
      increased cancer risk under multiple genetic models (CC vs. GG: OR = 1.37, 95 %
      CI 1.06-1.76; CC vs. CG: OR = 1.27, 95 % CI = 1.10-1.46; CC vs. CG + GG: OR =
      1.31, 95 % CI = 1.10-1.57). In subgroup analysis with different cancer types, the
      -31G>C polymorphism significantly increased the risk of colorectal, gastric, and
      urothelial cancers, while this SNP remarkably decreased the susceptibility to
      hepatocellular carcinoma. Further stratification analysis by ethnicity showed an
      increasing cancer risk in the Asian population (CC vs. GG: OR = 1.61, 95 % CI
      1.17-2.21; CC vs. CG: OR = 1.31, 95 % CI 1.12-1.53; CC vs. CG + GG: OR = 1.43, 95
      % CI 1.16-1.77) but not in Europeans. CONCLUSIONS: The survivin -31G>C
      polymorphism is associated with elevated cancer risk, especially among
      colorectal, gastric, and urothelial cancers and Asian populations.

PMID- 24077841
TI  - BBGRE: brain and body genetic resource exchange.
AB  - Studies of copy number variation (genomic imbalance) are providing insight into
      both complex and Mendelian genetic disorders. Array comparative genomic
      hybridization (array CGH), a tool for detecting copy number variants at a
      resolution previously unattainable in clinical diagnostics, is increasingly used
      as a first-line test at clinical genetics laboratories. Many copy number variants
      are of unknown significance; correlation and comparison with other patients will
      therefore be essential for interpretation. We present a resource for clinicians
      and researchers to identify specific copy number variants and associated
      phenotypes in patients from a single catchment area, tested using array CGH at
      the SE Thames Regional Genetics Centre, London. User-friendly searching is
      available, with links to external resources, providing a powerful tool for the
      elucidation of gene function. We hope to promote research by facilitating
      interactions between researchers and patients. The BBGRE (Brain and Body Genetic
      Resource Exchange) resource can be accessed at the following website:
      http://bbgre.org DATABASE URL: http://bbgre.org.

PMID- 24077843
TI  - The effect of 7-ketocholesterol and 25-hydroxycholesterol on the integrity of the
      human aortic endothelial and intestinal epithelial barriers.
AB  - OBJECTIVE AND DESIGN: The damage of barrtier tissues, such as the vascular
      endothelium and intestinal epithelium, may lead to disturbances of local immune
      homeostasis. The aim of the study was to assess and compare the effect of
      oxidized cholesterols (7-ketocholesterol and 25-hydroxycholesterol) on the
      barrier properties of human primary aortic endothelium (HAEC) and intestinal
      epithelium Caco-2 cells using a realtime cell electric impedance sensing system
      (RTCA-DP). MATERIALS AND METHODS: HAEC and Caco-2 cells were stimulated with 7
      ketocholesterol and 25-hydroxycholesterol by the RTCA-DP system. Apoptosis was
      assessed by flow cytometry and cell monolayer morphology was assessed under a
      light microscope. RESULTS: 7-ketocholesterol decreased impedance (nCI) in both
      the endothelium and epithelium. However, the decrease was more profound in the
      endothelium. Similarly, although 25-hydroxycholesterol decreased nCI in both the
      endothelium and epithelium, the effect was weaker than that of 7-ketocholesterol,
      which caused extensive damage to the endothelial monolayer, while 25
      hydroxycholesterol caused partial damage and did not affect the epithelial
      monolayer. 7-ketocholesterol, but not 25-hydroxycholesterol, increased
      endothelial cell apoptosis and decreased the viability of endothelial cells.
      However, 7-ketocholesterol and 25-hydroxycholesterol decreased epithelial cell
      apoptosis and increased viability. CONCLUSION: Oxidized cholesterols destroy the
      HAEC, but not the Caco-2 epithelial barrier, via cell apoptosis dependent on the
      site of oxidation. Damage to the endothelium by oxidized cholesterol may disrupt
      local homeostasis and provide open access to inner parts of the vascular wall for
      lipids, other peripheral blood-derived agents, and immune cells, leading to
      inflammation and atherogenesis.

PMID- 24077844
TI  - Novel exon 2 alpha spectrin mutation and intragenic crossover: three
      morphological phenotypes associated with four distinct alpha spectrin defects.
AB  - Hereditary pyropoikilocytosis is a severe hemolytic anemia caused by spectrin
      deficiency and defective spectrin dimer self-association, typically found in
      African populations. We describe two Utah families of northern European ancestry
      including 2 propositi with atypical non-microcytic hereditary pyropoikilocytosis,
      7 hereditary elliptocytosis members and one asymptomatic carrier. The underlying
      molecular defect is a novel mutation in the alpha(alpha) spectrin gene,
      SPTA(R34P) that impairs spectrin tetramer formation. It is inherited in trans to
      the hypomorphic SPTA(alphaLELY) in the 2 propositi and 5 of 7 hereditary
      elliptocytosis individuals indicating that SPTA(alphaLELY) is not the sole
      determinant of the variable clinical expression. alpha Spectrin mRNA was mildly
      decreased in all hereditary elliptocytosis subjects, whereas both hereditary
      pyropoikilocytosis propositi had a severe decrease to ~10% of normal. Genotyping
      identified a unique SPTA intragenic crossover and uniparental disomy in one
      hereditary elliptocytosis individual. Two additional crossover events
      demonstrated the susceptibility of SPTA gene to rearrangement and revealed a
      novel segregation of the two SPTA(alphaLELY) mutations. We conclude that the
      profound phenotypic heterogeneity in these families can be attributed to the
      SPTA(R34P) mutation in combination with: 1) inheritance in trans of either
      SPTA(alphaLELY); or 2) the wild-type SPTA; 3) a decrease of alpha spectrin mRNA;
      and 4) SPTA intragenic crossover. 

PMID- 24077845
TI  - Acquired ASXL1 mutations are common in patients with inherited GATA2 mutations
      and correlate with myeloid transformation.
AB  - Inherited or sporadic heterozygous mutations in the transcription factor GATA2
      lead to a clinical syndrome characterized by non-tuberculous mycobacterial and
      other opportunistic infections, a severe deficiency in monocytes, B cells and
      natural killer cells, and progression from a hypocellular myelodysplastic
      syndrome to myeloid leukemias. To identify acquired somatic mutations associated
      with myeloid transformation in patients with GATA2 mutations, we sequenced the
      region of the ASXL1 gene previously associated with transformation from
      myelodysplasia to myeloid leukemia. Somatic, heterozygous ASXL1 mutations were
      identified in 14/48 (29%) of patients with GATA2 deficiency, including four out
      of five patients who developed a proliferative chronic myelomonocytic leukemia.
      Although patients with GATA2 mutations had a similarly high incidence of myeloid
      transformation when compared to previously described patients with ASXL1
      mutations, GATA2 deficiency patients with acquired ASXL1 mutation were
      considerably younger, almost exclusively female, and had a high incidence of
      transformation to a proliferative chronic myelomonocytic leukemia. These patients
      may benefit from allogeneic hematopoietic stem cell transplantation before the
      development of acute myeloid leukemia or chronic myelomonocytic leukemia.
      (ClinicalTrials.gov identifier NCT00018044, NCT00404560, NCT00001467,
      NCT00923364.). 

PMID- 24077846
TI  - Autologous transplantation for Philadelphia chromosome-positive acute
      lymphoblastic leukemia achieves outcomes similar to allogeneic transplantation:
      results of CALGB Study 10001 (Alliance).
AB  - Allogeneic stem cell transplantation is the standard approach to Philadelphia
      chromosome positive acute lymphoblastic leukemia. We hypothesized that imatinib
      plus sequential chemotherapy will result in significant leukemia cell
      cytoreduction in patients with Philadelphia chromosome positive acute
      lymphoblastic leukemia, allowing collection of normal hematopoietic stem cells
      uncontaminated by residual BCR/ABL1(+) lymphoblasts and thus reduce the
      likelihood of relapse after autologous stem cell transplantation for patients
      under 60 years of age without sibling donors. We enrolled 58 patients; 19
      underwent autologous and 15 underwent allogeneic stem cell transplantation on
      study. Imatinib plus sequential chemotherapy resulted in reverse-transcriptase
      polymerase chain reaction-negative stem cells in 9 patients and remained
      minimally positive in 4 (6 were not evaluable). Overall survival (median 6.0
      years vs. not reached) and disease-free survival (median 3.5 vs. 4.1 years) were
      similar between those who underwent autologous and those who underwent allogeneic
      stem cell transplantation. We conclude that autologous stem cell transplantation
      represents a safe and effective alternative for allogeneic stem cell
      transplantation in Philadelphia chromosome positive acute lymphoblastic leukemia
      patients without sibling donors (clinicaltrials.gov identifier:00039377). 

PMID- 24077847
TI  - Age effects on extracellular matrix production of vocal fold scar fibroblasts in
      rats.
AB  - Vocal fold (VF) fibroblasts are the central subject of interest in fibrogenesis
      and wound healing after VF injury. Scar fibroblasts (SF) exhibit an aberrant
      production of several extracellular matrix (ECM) components which lead either to
      VF fibrosis or scarless wound healing. This study aimed to investigate the role
      of age at the time of injury on ECM production of SF. This is designed as an
      animal study. VF injury was established unilaterally in eight male Sprague-Dawley
      rats [3 months of age (n = 4), 11 months of age (n = 4)], while the other side
      was left intact. Three months after injury the larynges were excised and
      fibroblasts were extracted from VF [normal fibroblasts (NF)-scar fibroblasts
      (SF)] and cultured in vitro. After first passage, VF fibroblasts were plated in
      24-well plates and levels of hyaluronic acid (HA) and collagen type I were
      determined enzymatically from supernatant after 24 and 72 h. Cultured SF from
      younger animals produced significantly higher levels of HA compared to NF
      fibroblasts from the same animals. HA concentrations of the older animals did not
      differ significantly between the NF and SF cultures, but the range in SF cultures
      was large. In contrast to previous studies, we found that even 3 months after VF
      injury cultured SF from young animals expressed higher levels of HA in comparison
      to SF from older animals. No difference in collagen levels were observed between
      the younger and older animals. Age of animals is an essential factor during VF
      healing and has to be considered for study design.

PMID- 24077849
TI  - Positive charge loading at protein termini is due to membrane protein topology,
      not a translational ramp.
AB  - In the great majority of genomes, the use of positive charge increases, on
      average, approaching protein N-termini. Such charged residues slow ribosomes by
      interacting with the negatively charged exit tunnel. This has been proposed to be
      selectively advantageous as it provides an elongation speed ramp at translational
      starts. Positive charges, however, are known to orientate proteins in membranes
      by the positive-inside rule whereby excess charge lies on the cytoplasmic side of
      the membrane. Which of these two models better explains the N-terminal loading of
      positively charged amino acids? We find strong evidence that the tendency for
      average positive charge use to increase at termini is exclusively due to membrane
      protein topology: 1) increasing N-terminal positive charge is not found in
      cytosolic proteins, but in transmembrane ones with cytosolic N-termini, with
      signal sequences contributing additional charge; 2) positive charge density at N
      termini corresponds to the length of cytoplasmically exposed transmembrane tails,
      its usage increasing just up until the membrane; 3) membrane-related patterns are
      repeated at C-termini, where no ramp is expected; and 4) N-terminal positive
      charge patterns are no different from those seen internally in proteins in
      membrane-associated domains. The overall apparent increase in positive charge
      across all N-termini results from membrane proteins using positive charge
      adjacent to the cytosolic leaflet, combined with a skewed distribution of where N
      termini cross the plasma membrane; 5) while Escherichia coli was predicted to
      have a 5' ribosomal occupancy ramp of at least 31 codons, in contrast to what is
      seen in yeast, we find in ribosomal footprinting data no evidence for such a
      ramp. In sum, we find no need to invoke a translational ramp to explain the
      rising positive charge densities at N-termini. The membrane orientation model
      makes a full account of the trend. 

PMID- 24077848
TI  - An empirical test of convergent evolution in rhodopsins.
AB  - Rhodopsins are photochemically reactive membrane proteins that covalently bind
      retinal chromophores. Type I rhodopsins are found in both prokaryotes and
      eukaryotic microbes, whereas type II rhodopsins function as photoactivated G
      protein coupled receptors (GPCRs) in animal vision. Both rhodopsin families share
      the seven transmembrane alpha-helix GPCR fold and a Schiff base linkage from a
      conserved lysine to retinal in helix G. Nevertheless, rhodopsins are widely cited
      as a striking example of evolutionary convergence, largely because the two
      families lack detectable sequence similarity and differ in many structural and
      mechanistic details. Convergence entails that the shared rhodopsin fold is so
      especially suited to photosensitive function that proteins from separate origins
      were selected for this architecture twice. Here we show, however, that the
      rhodopsin fold is not required for photosensitive activity. We engineered
      functional bacteriorhodopsin variants with novel folds, including radical
      noncircular permutations of the alpha-helices, circular permutations of an eight
      helix construct, and retinal linkages relocated to other helices. These results
      contradict a key prediction of convergence and thereby provide an experimental
      attack on one of the most intractable problems in molecular evolution: how to
      establish structural homology for proteins devoid of discernible sequence
      similarity. 

PMID- 24077851
TI  - Conventional evaluations of improvement interventions: more trials or just more
      tribulations?

PMID- 24077850
TI  - Reducing unnecessary urinary catheter use and other strategies to prevent
      catheter-associated urinary tract infection: an integrative review.
AB  - BACKGROUND: Catheter-associated urinary tract infections (CAUTI) are costly,
      common and often preventable by reducing unnecessary urinary catheter (UC) use.
      METHODS: To summarise interventions to reduce UC use and CAUTIs, we updated a
      prior systematic review (through October 2012), and a meta-analysis regarding
      interventions prompting UC removal by reminders or stop orders. A narrative
      review summarises other CAUTI prevention strategies including aseptic insertion,
      catheter maintenance, antimicrobial UCs, and bladder bundle implementation.
      RESULTS: 30 studies were identified and summarised with interventions to prompt
      removal of UCs, with potential for inclusion in the meta-analyses. By meta
      analysis (11 studies), the rate of CAUTI (episodes per 1000 catheter-days) was
      reduced by 53% (rate ratio 0.47; 95% CI 0.30 to 0.64, p<0.001) using a reminder
      or stop order, with five studies also including interventions to decrease initial
      UC placement. The pooled (nine studies) standardised mean difference (SMD) in
      catheterisation duration (days) was -1.06 overall (p=0.065) including a
      statistically significant decrease in stop-order studies (SMD -0.37; p<0.001) but
      not in reminder studies (SMD, -1.54; p=0.071). No significant harm from catheter
      removal strategies is supported. Limited research is available regarding the
      impact of UC insertion and maintenance technique. A recent randomised controlled
      trial indicates antimicrobial catheters provide no significant benefit in
      preventing symptomatic CAUTIs. CONCLUSIONS: UC reminders and stop orders appear
      to reduce CAUTI rates and should be used to improve patient safety. Several
      evidence-based guidelines have evaluated CAUTI preventive strategies as well as
      emerging evidence regarding intervention bundles. Implementation strategies are
      important because reducing UC use involves changing well-established habits.

PMID- 24077853
TI  - Improved terminology for experimental field-flow fractionation.

PMID- 24077852
TI  - The immunogenicity of a novel cytotoxic T lymphocyte epitope from tumor antigen
      PL2L60 could be enhanced by 4-chlorophenylalanine substitution at position 1.
AB  - PIWIL2, a member of PIWI/AGO family, is expressed in germline stem cells and
      precancerous stem cells, but not in adult somatic cells. PIWIL2 plays an
      important role in tumor development. It is considered as a cancer-testis antigen
      (CT80). It has been reported that the spliced fragment of PIWIL2, PL2L60, was
      widely expressed in cancer cell lines. In this study, HLA-A2-restricted epitopes
      from PL2L60 were predicted by online tools. To improve the activity of the native
      epitope, a candidate peptide P281 with potent binding affinity was chosen to
      investigate the modification strategy. A series of aromatic amino acids were
      introduced to substitute the first residue of P281. Then, we tested the binding
      affinity and stability of the peptide analogs and their ability to elicit
      specific immune responses both in vitro and in vivo. Our results indicated that
      the cytotoxic T lymphocytes (CTLs) induced by [4-Cl-Phe1]P281 could elicit more
      potent activities than that of P281 and other analogs. The CTLs induced by this
      analog could lyze target cells in HLA-A2-restricted and antigen-specific manners.
      [4-Cl-Phe1]P281 also showed the best resistance against degradation in human
      serum. In conclusion, the introduction of the unnatural amino acid, 4-Cl-Phe,
      into the first position could enhance the activity of the native epitope to
      induce cytotoxic T lymphocytes. It might be a good strategy to modify other
      promising native epitopes. The novel epitopes identified in this study could be
      used as novel candidates to the immunotherapy of HLA-A2 positive patients with
      tumors expressing PL2L60.

PMID- 24077854
TI  - A novel electrochemical method for efficient reduction of disulfide bonds in
      peptides and proteins prior to MS detection.
AB  - A novel electrochemical (EC) method for fast and efficient reduction of the
      disulfide bonds in proteins and peptides is presented. The method does not use
      any chemical agents and is purely instrumental. To demonstrate the performance of
      the EC reactor cell online with electrospray mass spectrometry, insulin and
      somatostatin were used as model compounds. Efficient reduction is achieved in
      continuous infusion mode using an EC reactor cell with a titanium-based working
      electrode. Under optimized conditions, the presented method shows almost complete
      reduction of insulin and somatostatin. The method does not require any special
      sample preparation, and the EC reactor cell makes it suitable for automation.
      Online EC reduction followed by collision-induced dissociation fragmentation of
      somatostatin showed more backbone cleavages and improved sequence coverage. By
      adjusting the settings, the EC reaction efficiency was gradually changed from
      partial to full disulfide bonds reduction in alpha-lactalbumin, and the expected
      shift in charge state distribution has been demonstrated. The reduction can be
      controlled by adjusting the square-wave pulse, flow rate or mobile phase
      composition. We have shown the successful use of an EC reactor cell for fast and
      efficient reduction of disulfide bonds for online mass spectrometry of proteins
      and peptides. The possibility of online and gradual disulfide bond reduction adds
      a unique dimension to characterization of disulfide bonds in mid-and top-down
      proteomics applications.

PMID- 24077855
TI  - An in vitro experiment on the interaction of charcoal or wheat bran with 11-nor-9
      carboxy-Delta(9)-tetrahydrocannabinol and its glucuronide.
AB  - The rather long yet variable terminal half-lives and detection times since last
      use of urinary cannabinoids may partly be attributed to their enterohepatic
      circulation which generally can be interrupted or restricted by chemical
      adsorbents. Therefore, an in vitro experiment was performed to study the
      adsorption/binding of 11-nor-9-carboxy-Delta9-tetrahydrocannabinol (THC-COOH) and
      its glucuronide to activated charcoal and wheat bran; remaining concentrations
      were determined by liquid chromatography/tandem mass spectrometry.
      Adsorption/binding of 1,000 ng/mL of free or conjugated THC-COOH was complete
      using as little as 5 mg of charcoal whereas adsorption/binding to wheat bran
      increased with increasing amounts. Taking of remedies affecting enterohepatic
      recycling of THC-COOH and its glucuronide may challenge interpretation of
      cannabinoid concentrations used to detect or assess frequency of drug use or the
      time since last drug consumption.

PMID- 24077856
TI  - Immunocytochemical localization of TASK-3 protein (K2P9.1) in the rat brain.
AB  - Among all K2P channels, TASK-3 shows the most widespread expression in rat brain,
      regulating neuronal excitability and transmitter release. Using a recently
      purified and characterized polyclonal monospecific antibody against TASK-3, the
      entire rat brain was immunocytochemically analyzed for expression of TASK-3
      protein. Besides its well-known strong expression in motoneurons and
      monoaminergic and cholinergic neurons, TASK-3 expression was found in most
      neurons throughout the brain. However, it was not detected in certain neuronal
      populations, and neuropil staining was restricted to few areas. Also, it was
      absent in adult glial cells. In hypothalamic areas, TASK-3 was particularly
      strongly expressed in the supraoptic and suprachiasmatic nuclei, whereas other
      hypothalamic nuclei showed lower protein levels. Immunostaining of hippocampal
      CA1 and CA3 pyramidal neurons showed strongest expression, together with clear
      staining of CA3 mossy fibers and marked staining also in the dentate gyrus
      granule cells. In neocortical areas, most neurons expressed TASK-3 with a
      somatodendritic localization, most obvious in layer V pyramidal neurons. In the
      cerebellum, TASK-3 protein was found mainly in neurons and neuropil of the
      granular cell layer, whereas Purkinje cells were only faintly positive.
      Particularly weak expression was demonstrated in the forebrain. This report
      provides a comprehensive overview of TASK-3 protein expression in the rat brain.

PMID- 24077857
TI  - Prednisolone induces microglial activation in the subnucleus caudalis of the rat
      trigeminal sensory complex.
AB  - Prednisolone is a member of synthetic glucocorticoids which are widely used to
      treat chronic inflammatory diseases. In this study, neuronal degeneration and
      cell death, and glial reaction were investigated in the rat trigeminal ganglion
      (TG) and brainstem after subcutaneous injection of prednisolone for 7 days.
      Expression of c-Jun activating transcription factor 3 and caspase-3 was absent or
      infrequent in the TG, and cranial sensory and motor nuclei of saline- and
      prednisolone-treated animals. In these animals, distribution of calcitonin gene
      related peptide-immunoreactive (-IR) neurons and nerve fibers was similar in the
      brainstem. In addition, the number of Iba1- and glial fibrillary acidic protein
      (GFAP)-IR cells with some processes in the brainstem was barely affected by
      prednisolone treatment. However, the treatment increased ramification of Iba1-IR
      processes in the subnucleus caudalis of the trigeminal sensory complex.
      Prednisolone scarcely influenced the morphology of GFAP-IR cells in the
      brainstem. Expression of p38 mitogen-activated protein kinase was very rare in
      the brainstem of saline- and prednisolone-treated animals. The present study
      suggests that microglia are activated by prednisolone in the subnucleus caudalis
      of the trigeminal sensory complex. The glucocorticoid may affect nociceptive
      transmission in the brainstem.

PMID- 24077858
TI  - The effect of preoperative anxiety on postoperative analgesia   and anesthesia
      recovery in patients undergoing laparascopic   cholecystectomy.

PMID- 24077859
TI  - Perioperative management of Eagle syndrome  complicated by carotid artery
      dissection.

PMID- 24077860
TI  - Parametric comparisons of intracranial mechanical responses from three validated
      finite element models of the human head.
AB  - A number of human head finite element (FE) models have been developed from
      different research groups over the years to study the mechanisms of traumatic
      brain injury. These models can vary substantially in model features and
      parameters, making it important to evaluate whether simulation results from one
      model are readily comparable with another, and whether response-based injury
      thresholds established from a specific model can be generalized when a different
      model is employed. The purpose of this study is to parametrically compare
      regional brain mechanical responses from three validated head FE models to test
      the hypothesis that regional brain responses are dependent on the specific head
      model employed as well as the region of interest (ROI). The Dartmouth Scaled and
      Normalized Model (DSNM), the Simulated Injury Monitor (SIMon), and the Wayne
      State University Head Injury Model (WSUHIM) were selected for comparisons. For
      model input, 144 unique kinematic conditions were created to represent the range
      of head impacts sustained by male collegiate hockey players during play. These
      impacts encompass the 50th, 95th, and 99th percentile peak linear and rotational
      accelerations at 16 impact locations around the head. Five mechanical variables
      (strain, strain rate, strain * strain rate, stress, and pressure) in seven ROIs
      reported from the FE models were compared using Generalized Estimating Equation
      statistical models. Highly significant differences existed among FE models for
      nearly all output variables and ROIs. The WSUHIM produced substantially higher
      peak values for almost all output variables regardless of the ROI compared to the
      DSNM and SIMon models (p < 0.05). DSNM also produced significantly different
      stress and pressure compared with SIMon for all ROIs (p < 0.05), but such
      differences were not consistent across ROIs for other variables. Regardless of FE
      model, most output variables were highly correlated with linear and rotational
      peak accelerations. The significant disparities in regional brain responses
      across head models regardless of the output variables strongly suggest that model
      predicted brain responses from one study should not be extended to other studies
      in which a different model is utilized. Consequently, response-based injury
      tolerance thresholds from a specific model should not be generalized to other
      studies either in which a different model is used. However, the similar
      relationships between regional responses and the linear/rotational peak
      accelerations suggest that each FE model can be used independently to assess
      regional brain responses to impact simulations in order to perform statistical
      correlations with medical images and/or well-selected experiments with documented
      injury findings.

PMID- 24077861
TI  - Accumulation of oocytes from a few modified natural cycles to improve IVF
      results: a pilot study.
AB  - PURPOSE: To evaluate the role of co-transfer of embryos derived from vitrified
      oocytes accumulated during the previous modified natural cycles and an embryo
      developed from the last one as an alternative to repetitive single embryo
      transfer ina fresh modified natural cycle. METHODS: Thirty-six patients underwent
      ICSI procedure with three frozen natural oocytes supplemented by a fresh one
      obtained from the fourth modified natural cycle. Thirty-one controls received at
      least three consecutive single embryo transfer in a fresh modified natural cycle.
      RESULTS: In the study group the oocyte retrieval, survival and total
      fertilization rate were 73.0 %, 78.1 %, and 64.5 %, respectively. Fifty-two
      embryos were transferred in 29 transfers. In the control group the oocyte
      retrieval and fertilization rate was 77.4 % and 83.7 %, respectively. Fifty
      single embryo transfers were performed. Of a total 14 pregnancies obtained in the
      study group 10 were defined as clinical and 4 as abortions. In the control group
      a total of 8 single clinical pregnancies and 2 miscarriages were encountered. The
      overall (20.0 % vs 48.2 %) and the clinical (16.0 % vs 34.4 %) pregnancy rate
      were significantly higher in the study group having cumulative embryo transfer
      following the oocyte accumulation. CONCLUSIONS: These data demonstrate that the
      co-transfer of embryos derived from vitrified oocytes accumulated during the
      previous modified natural cycles and an embryo developed from the last fresh
      modified natural cycle assure an excellent clinical outcome with the overall and
      clinical pregnancy rate significantly higher compared to the repetitive single
      embryo transfer in a fresh modified natural cycle.

PMID- 24077862
TI  - Patient classification and hospital reimbursement for inguinal  hernia repair: a
      comparison across 11 European countries.
AB  - PURPOSE: This comparative study examines the categorisation of patients
      undergoing surgical repair of inguinal hernia in the diagnosis-related group
      (DRG) systems of 11 European countries (Austria, England, Estonia, Finland,
      France, Germany, Ireland, the Netherlands, Poland, Spain and Sweden).
      Understanding the design and operation of DRG systems for this common surgical
      procedure is important, given their increasing use internationally for hospital
      reimbursement and performance measurement. METHODS: A common definition was used
      to identify inguinal hernia patients and the corresponding data were extracted
      from national databases. The analysis compared the variables and algorithms for
      classifying these patients to DRGs across the participating countries, as well as
      the number, composition and relative resource intensity of groups. An index case
      and six standardised vignettes were grouped using each country's DRG system and
      the associated quasi-prices were calculated. RESULTS: The number of groups to
      which inguinal hernia patients are assigned is typically three or four, but
      ranges from two in Poland to ten in France. In most systems, categorising
      patients is contingent on procedure, principal and secondary diagnoses, and age,
      with treatment setting (day case/inpatient) being less common. Added to these,
      the French system also incorporates length of stay and whether the patient died.
      More resource intensive DRGs generally contained patients who were older, treated
      as inpatients, did not die, had (more severe) complications and/or co
      morbidities, and/or underwent laparoscopic repair. There are cross-country
      disparities in day case rates and the use of laparoscopic repairs. CONCLUSIONS:
      The categorisation of inguinal hernia patients varies across the 11 European DRG
      systems under study. By highlighting the main differences across these systems,
      this comparative analysis allows the relevant decision makers to assess the
      adequacy and specificity of their own DRG systems.

PMID- 24077863
TI  - Early psychologically informed interventions for workers at risk for pain-related
      disability: does matching treatment to profile improve outcome?
AB  - PURPOSE: This randomized controlled trial had two main aims. The first aim was to
      investigate the effect of early preventive, psychologically informed,
      interventions for pain-related disability. The second aim was explore whether
      people who are matched to an intervention specifically targeting their
      psychological risk profile had better outcomes than people who were not matched
      to interventions. METHODS: A total of 105 participants were recruited from their
      workplace, screened for psychological risk factors and classified as being at
      risk for long-term pain-related disability. They were subgrouped into one of
      three groups based on their psychological profile. Three behaviorally oriented
      psychological interventions were developed to target each of the three risk
      profiles. Half of the participants were assigned a matched intervention developed
      to target their specific profile, and half were assigned an unmatched
      intervention. After treatment, repeated measure ANOVAs and v2 tests were used to
      determine if treatments had an effect on primary and secondary outcomes including
      perceived disability, sick leave, fear and avoidance, pain catastrophizing and
      distress, and if matched participants had better outcomes than did unmatched.
      RESULTS: Treatments had effects on all outcome variables (effect sizes d ranging
      between 0.23 and 0.66), but matched participants did not have better outcomes
      than unmatched. CONCLUSIONS: Early, preventive interventions have an impact on a
      number of outcome variables but it is difficult to realize a matching procedure.
      More in-depth research of the process of matching is needed.

PMID- 24077864
TI  - Perspectives in anaesthesia for cancer surgery.
AB  - BACKGROUND: It is a fact that inflammatory scores are important prognostic
      factors in cancer surgery. Many data have been published last year showing that
      inflammation is a causative event in many cancers and a concomitant event in all
      malignant tumours. MONITORING OF THE INFLAMMATION: What is new is that we can
      assess inflammatory status during the preoperative period of our cancer patients
      with simple and widely available parameters, such as the neutrophil/lymphocyte
      ratio. This kind of biomarkers will be helpful, for the clinicians, to stratify
      the patients and, for the researcher, to incorporate it in clinical trials.
      RATIONALE FOR TRIALS AFTER DATABASE ANALYSES: Promising clinical trials, focusing
      on perioperative inflammation, are ongoing. Rationale for these trials came from
      database analyses. This kind of analyses must be extended to follow the long-term
      effects of our interventions. NON-STEROIDAL ANTI-INFLAMMATORY DRUGS: We have
      shown a correlation between non-steroidal anti-inflammatory drugs, especially
      ketorolac, and improved outcome (metastasis-free survival and/or overall
      survival) in breast and lung cancer patients. CONCLUSION: Focusing on a high-risk
      group with preoperative inflammation could lead to a clinical trial to test the
      effect of ketorolac on cancer outcome.

PMID- 24077865
TI  - Treatment outcomes of transcatheter arterial chemoembolization combined with
      local ablative therapy versus monotherapy in hepatocellular carcinoma: a meta
      analysis.
AB  - PURPOSE: To evaluate the effectiveness comparing the combination of TACE with
      local ablative therapy and monotherapy on the treatment of HCC using meta
      analytical techniques. METHODS: Randomized controlled trials and clinical studies
      comparing TACE plus local ablative therapy with monotherapy for HCC were included
      in this meta-analysis. Response rate, 1-, 2-, 3-, and 5-year survival rate, and
      overall survival (OS) were analyzed and compared. RESULTS: Eighteen studies
      included a total of 2,120 patients with HCC 1,071 and 1,049 patients for
      treatment with combination therapy and monotherapy, respectively. The combination
      therapy group had a significantly better survival in terms of 1-, 2-, 3-, and 5
      year survival rate (RR 1.10, 95 % CI 1.03-1.18, P = 0.005; RR 1.20, 95 % CI 1.10
      1.30, P < 0.0001; RR 1.43, 95 % CI 1.18-1.73, P < 0.0001; RR 1.40, 95 % CI 1.22
      1.61, P < 0.0001, respectively), OS (HR 0.66, 95 % CI 0.51-0.85, P = 0.001), and
      response rate (RR 1.54, 95 % CI 1.09-2.18, P = 0.013) than that monotherapy group
      in patients with HCC. CONCLUSIONS: The meta-analysis indicates that the
      combination of TACE with local ablative therapy was superior to monotherapy in
      the treatment for patients with HCC.

PMID- 24077866
TI  - Human osteoblast damage after antiseptic treatment.
AB  - PURPOSE: Antiseptics are powerful medical agents used for wound treatment and
      decontamination and have a high potential for defeating joint infections in
      septic surgery. Both chlorhexidine and polyhexanide are frequently used in
      clinical practice and have a broad antimicrobial range, but their effect on human
      osteoblasts has not been sufficiently studied. Our objective was to investigate
      the toxic effects of polyhexanide and chlorhexidine on human osteoblasts in vitro
      to evaluate their clinical applicability in septic surgery. METHODS: We isolated
      and cultivated human osteoblasts in vitro and assayed the toxic effects of
      chlorhexidine 0.1% and polyhexanide 0.04%, concentrations commonly applied in
      clinical practice. Toxicity analysis was performed by visualisation of cell
      structure, lactate dehydrogenase (LDH) activity and evaluation of vital cells.
      Toxicity was evaluated by microscopic inspection of cell morphology, trypan blue
      staining and determination of LDH release. RESULTS: Damaged cell structure could
      be shown by microscopy. Both antiseptics promoted LDH activity after incubation
      with osteoblasts. The evaluation of vital osteoblasts showed a significant
      decrease of vital cells. CONCLUSIONS: Both antiseptics induced significant cell
      death of osteoblasts at optimum exposure. We therefore recommend cautious use of
      polyhexanide and chlorhexidine in septic surgery to avoid severe osteoblast
      toxicity.

PMID- 24077867
TI  - Locking versus non-locking neutralization plates for treatment of lateral
      malleolar fractures: a randomized controlled trial.
AB  - PURPOSE: The reduction of periosteal compression through the use of a locking
      plate may minimize disturbances of bone blood supply and may improve the rate of
      bone union. A single-centre, assessor blinded randomized controlled trial was
      conducted to compare the clinical effectiveness of a locking plate and a non
      locking plate. METHODS: A total of 52 patients with AO/OTA 44B lateral malleolar
      fractures were included in this study. All patients underwent surgical fixation
      using a lag screw and neutralization plate. An identical treatment protocol was
      used in all patients, with exception of plate selection. The rate of radiographic
      bone union, defined as the complete disappearance of fracture lines confirmed
      through anteroposterior, lateral, and internal oblique views was compared at
      three, six, and 12 months following surgery. In addition, the Medical Outcomes 36
      Item Short-Form Health Survey (SF-36) score, the time required for resolution of
      tenderness at the fracture site and the complication rate were evaluated.
      RESULTS: Twenty-three patients were randomly assigned to undergo fixation using a
      locking plate, and 29 patients were assigned to undergo fixation using a non
      locking plate. Intention-to-treat analysis showed no difference in the
      radiographic bone union rate of fibula, SF-36 score, the time for resolution of
      tenderness at the fracture site and complication rates. CONCLUSION: No
      differences were observed in patients with AO/OTA 44B lateral malleolar fractures
      undergoing fixation with a locking versus non-locking neutralization plate.

PMID- 24077868
TI  - Vocal cord paralysis caused by stingray.
AB  - Foreign bodies in the oral cavity and pharynx are commonly encountered in the
      emergency room and outpatient departments, and the most frequently observed of
      these foreign bodies are fish bones. Among the possible complications resulting
      from a pharyngeal foreign body, vocal cord fixation is extremely rare, with only
      three cases previously reported in the English literature. The mechanisms of
      vocal cord fixation can be classified into mechanical articular fixation, direct
      injury of the recurrent laryngeal nerve, or recurrent laryngeal nerve paralysis
      secondary to inflammation. The case discussed here is different from previous
      cases. We report a rare case of vocal cord paralysis caused by the venom of a
      stingray tail in the hypopharynx.

PMID- 24077869
TI  - Transoral robotic surgery of the central skull base: preclinical investigations.
AB  - In this study we explored possible applications of the da Vinci system in
      approaching the skull base at optic chiasm level on two cryopreserved cadavers,
      using an entirely transoral robotic technique (TORS). We used a standard 12 mm
      endoscopy and 8 mm terminals. Bone drilling was performed manually. The da Vinci
      system is equipped with very good illumination and 3D viewing, thus providing
      excellent vision and great maneuverability even in the less accessible areas of
      the skull. Our experience demonstrates that an entirely transoral skull base
      robotic approach to this complex anatomical region has many advantages as
      compared to traditional techniques.

PMID- 24077870
TI  - The effect of corticosteroid therapy on cyclooxygenase 2, vascular endothelial
      growth factor, and inducible nitric oxide synthase expression levels in nasal
      polyposis.
AB  - Nasal and oral corticosteroid therapy is the ultimate treatment for sinonasal
      polyposis. Although there are numerous clinical studies regarding the factors
      associated with the formation of nasal polyposis, there is not enough literature
      on how these factors are influenced by steroid treatment. Twenty-one patients
      that had no prior medical therapy for nasal polyposis or had received medical
      therapy at least 6 months earlier were included in the study. Patients were
      treated with oral and nasal corticosteroid therapy. Nasal polyp biopsies were
      taken before and after medical treatment and immunohistochemical staining for
      cyclooxygenase 2 (COX-2), vascular endothelial growth factor (VEGF) and inducible
      nitric oxide synthase (iNOS) were applied to the specimens. In this study, we
      tried to demonstrate the effects of corticosteroid therapy on nasal polyposis
      tissue immunohistochemically. There was no change at immunohistochemical
      expression level of COX-2; however, the decline of immunohistochemical expression
      levels of VEGF and iNOS was statistically significant. Short-term steroid therapy
      does not affect COX-2 level of the nasal polyposis tissue, but has an influence
      on iNOS and VEGF levels. Our findings were harmonious with those of the previous
      studies of the literature. Further studies are needed to demonstrate the long
      term effects with a larger patient group.

PMID- 24077871
TI  - Effectiveness of olfactory rehabilitation according to a structured protocol with
      potential of regaining pre-operative levels in laryngectomy patients using nasal
      airflow-inducing manoeuvre.
AB  - This pilot study aims to evaluate the effectiveness of the Nasal Airflow-Inducing
      Manoeuvre (NAIM) when employing a structured protocol as well as investigate if
      early rehabilitation has the potential to return olfaction to pre-operative
      levels in patients undergoing laryngectomy following laryngeal cancer.
      Prospective study of cases conducted during 1 year, 2009-2010, at the Department
      of Ear-, Nose and Throat at Sahlgrenska University Hospital, Gothenburg, Sweden.
      Ten patients with laryngeal cancer and about to undergo laryngectomy were
      identified, of which four were included in the study. The remaining six patients
      were unfit to participate (n = 4) or declined participation (n = 2). Testing was
      conducted pre- and post-operatively and at each NAIM training session. Patients
      received three initial NAIM sessions followed by reinforcement training at 3, 6
      and 12 months. Measures included Scandinavian Odour-Identification Test (SOIT), a
      semi-structured interview and questionnaires including European Organisation for
      Research and Treatment of Cancer, QLQ-C30 and QLQ-H&N35. All patients were
      normosmic smellers according to SOIT at the study end-point. One patient reported
      higher SOIT scores at 12 months follow-up compared to pre-operatively. Remaining
      patients had scores close to that reported pre-operatively. Using subjective
      measures, olfaction improved in all patients with one patient's final score
      surpassing pre-operative scores. By implementing a structured protocol consisting
      of three training sessions early following laryngectomy with additional
      reinforcement sessions at 3, 6 and 12 months, NAIM is effective in terms of
      improving smelling ability. There also appears to be potential for restoring
      olfaction to a patient's pre-operative level as reflected by both olfactory
      testing and PRO instruments. However, larger studies are needed to further
      explore the findings highlighted by this study.

PMID- 24077872
TI  - Pharyngo-cutaneous fistula complicating laryngectomy in the chemo-radiotherapy
      organ-preservation epoch.
AB  - Pharyngo-cutaneous fistula is a serious complication of laryngectomy, with a
      significant associated morbidity and mortality. The oncologic success of organ
      preservation protocols with radiotherapy or chemo-radiotherapy for laryngeal
      carcinoma means laryngectomy is increasingly reserved for surgical salvage in the
      event of persistent or recurrent disease. A retrospective review of fistula
      incidence after laryngectomy in 171 patients in a UK tertiary referral centre
      over the last decade was conducted to identify trends in this complication in the
      epoch of non-surgical organ preservation. The overall fistula incidence following
      laryngectomy is 29.2% (50/171). Fistula incidence following salvage total
      laryngectomy is significantly higher than after primary total laryngectomy [19/51
      (37.3%) vs. 8/47 (17.0%), chi2 = 5.02, p = 0.03]. There is no significant effect
      of prior treatment on fistula incidence following laryngo-pharyngectomy or
      pharyngo-laryngo-oesophagectomy [14/39 (35.9%) vs. 9/27 (33.3%), chi2 = 0.05, p =
      0.83]. Prophylactic vascularised tissue flaps to reinforce the pharyngeal suture
      line may reduce fistula incidence and fistula severity in salvage total
      laryngectomy.

PMID- 24077873
TI  - NANOSCALE SELF-ASSEMBLY FOR DELIVERY OF THERAPEUTICS AND IMAGING AGENTS.
AB  - Self-assemblies are complex structures spontaneously organized from simpler
      subcomponents, primarily through noncovalent interactions. These structures are
      being exploited as delivery vehicles of therapeutic and imaging agents. They have
      two unique advantages in comparison to other vehicles: 1) they are able to assume
      complex structures that are difficult to attain by chemical synthesis, and 2) the
      dissociation of self-assembled structures can be triggered by external stimuli,
      which can serve as a mechanism of payload release. In this review, we discuss two
      naturally occurring (proteins and viral capsids) and five engineered self
      assemblies (vesicles, micelles, proteins, hydrogels, and inclusion complexes)
      that are under development for delivery of drugs and imaging agents. For each
      class of self-assembled supramolecular structures, we examine its structural and
      physicochemical properties, and potential applications within the context of
      assembly, loading, and payload release.

PMID- 24077874
TI  - A review of phosphate mineral nucleation in biology and geobiology.
AB  - Relationships between geological phosphorite deposition and biological apatite
      nucleation have often been overlooked. However, similarities in biological
      apatite and phosphorite mineralogy suggest that their chemical formation
      mechanisms may be similar. This review serves to draw parallels between two newly
      described phosphorite mineralization processes, and proposes a similar novel
      mechanism for biologically controlled apatite mineral nucleation. This mechanism
      integrates polyphosphate biochemistry with crystal nucleation theory. Recently,
      the roles of polyphosphates in the nucleation of marine phosphorites were
      discovered. Marine bacteria and diatoms have been shown to store and concentrate
      inorganic phosphate (Pi) as amorphous, polyphosphate granules. Subsequent release
      of these P reserves into the local marine environment as Pi results in
      biologically induced phosphorite nucleation. Pi storage and release through an
      intracellular polyphosphate intermediate may also occur in mineralizing oral
      bacteria. Polyphosphates may be associated with biologically controlled apatite
      nucleation within vertebrates and invertebrates. Historically, biological apatite
      nucleation has been attributed to either a biochemical increase in local Pi
      concentration or matrix-mediated apatite nucleation control. This review proposes
      a mechanism that integrates both theories. Intracellular and extracellular
      amorphous granules, rich in both calcium and phosphorus, have been observed in
      apatite-biomineralizing vertebrates, protists, and atremate brachiopods. These
      granules may represent stores of calcium-polyphosphate. Not unlike phosphorite
      nucleation by bacteria and diatoms, polyphosphate depolymerization to Pi would be
      controlled by phosphatase activity. Enzymatic polyphosphate depolymerization
      would increase apatite saturation to the level required for mineral nucleation,
      while matrix proteins would simultaneously control the progression of new
      biological apatite formation.

PMID- 24077875
TI  - Standardizing evaluation of pQCT image quality in the presence of subject
      movement: qualitative versus quantitative assessment.
AB  - Peripheral quantitative computed tomography (pQCT) is an essential tool for
      assessing bone parameters of the limbs, but subject movement and its impact on
      image quality remains a challenge to manage. The current approach to determine
      image viability is by visual inspection, but pQCT lacks a quantitative
      evaluation. Therefore, the aims of this study were to (1) examine the reliability
      of a qualitative visual inspection scale and (2) establish a quantitative motion
      assessment methodology. Scans were performed on 506 healthy girls (9-13 years) at
      diaphyseal regions of the femur and tibia. Scans were rated for movement
      independently by three technicians using a linear, nominal scale. Quantitatively,
      a ratio of movement to limb size (%Move) provided a measure of movement artifact.
      A repeat-scan subsample (n = 46) was examined to determine %Move's impact on bone
      parameters. Agreement between measurers was strong (intraclass correlation
      coefficient = 0.732 for tibia, 0.812 for femur), but greater variability was
      observed in scans rated 3 or 4, the delineation between repeat and no repeat. The
      quantitative approach found >=95% of subjects had %Move <25 %. Comparison of
      initial and repeat scans by groups above and below 25% initial movement showed
      significant differences in the >25 % grouping. A pQCT visual inspection scale can
      be a reliable metric of image quality, but technicians may periodically
      mischaracterize subject motion. The presented quantitative methodology yields
      more consistent movement assessment and could unify procedure across
      laboratories. Data suggest a delineation of 25% movement for determining whether
      a diaphyseal scan is viable or requires repeat.

PMID- 24077877
TI  - Assessing English literacy as a predictor of postschool outcomes in the lives of
      deaf individuals.
AB  - Lower English literacy achievement of deaf students is often hypothesized to be
      an impediment for successful adult life experiences. Yet, literacy practices that
      individuals engage in throughout their daily lives are much more complex than
      what school-based measures of English can capture and particularly so for deaf
      individuals. A national large-scale data set with a sample of over 1,000 deaf
      youths was used to assess what, precisely, standardized measures of literacy may
      predict in terms of postschool outcomes in three domains: life, employment, and
      education. Regression analyses indicate that these measures predicted some
      postschool outcomes, but not all, and if significant, only a small amount of
      variation in the outcomes was explained. Findings suggest that English literacy,
      particularly the narrow conceptualization of English literacy skills that are
      measured through school-based assessments, may not play a significant role in the
      lives of deaf individuals, contrary to expectations. 

PMID- 24077876
TI  - Impact of T cell selection methods in the success of clinical adoptive
      immunotherapy.
AB  - Chemotherapy and/or radiotherapy regular regimens used for conditioning of
      recipients of hematopoietic stem cell transplantation (SCT) induce a period of
      transient profound immunosuppression. The onset of a competent immunological
      response, such as the appearance of viral-specific T cells, is associated with a
      lower incidence of viral infections after haematopoietic transplantation. The
      rapid development of immunodominant peptide virus screening together with
      advances in the design of genetic and non-genetic viral- and tumoural-specific
      cellular selection strategies have opened new strategies for cellular
      immunotherapy in oncologic recipients who are highly sensitive to viral
      infections. However, the rapid development of cellular immunotherapy in SCT has
      disclosed the role of the T cell selection method in the modulation of functional
      cell activity and of in vivo secondary effects triggered following immunotherapy.

PMID- 24077878
TI  - The expression changes of vacuolar protein sorting 4B (VPS4B) following middle
      cerebral artery occlusion (MCAO) in adult rats brain hippocampus.
AB  - Vacuolar protein sorting 4 (VPS4), is a member of ATPases associated with diverse
      cellular activities protein family. VPS4 is composed of VPS4A and VPS4B, VPS4B
      plays an important role in the lysosomal degradation pathway, intracellular
      protein trafficking, virus budding and abscission of cytokinesis. However,
      information regarding its distribution and possible function in the central
      nervous system is limited. Therefore, we performed a middle cerebral artery
      occlusion (MCAO) in adult rats and detected the dynamic changes of VPS4B in
      hippocampus CA1 subregion. We found that the VPS4B expression was increased
      strongly after MCAO and reached the peak after 3 days. VPS4B mainly located in
      the cytoplasm of neurons, but not astrocytes and microglia. Moreover, there was a
      concomitant up-regulation of active caspase-3. In vitro studies indicated that
      the up-regulation of VPS4B may be involved in oxygen-glucose deprivation-induced
      PC12 cell death. And knock-down of VPS4B in cultured differentiated PC12 cells by
      siRNA showed that VPS4B promoted the expression of active caspase-3.
      Collectively, all these results and MTT assay suggested that the up-regulation of
      VPS4B played an important role in the pathophysiology after MCAO, and further
      research is needed to have a good understanding of its function and mechanism.

PMID- 24077879
TI  - A NOVEL DYNAMIC SYSTEM IN THE SPACE OF SPD MATRICES WITH APPLICATIONS TO
      APPEARANCE TRACKING.

PMID- 24077880
TI  - Negotiating markets for health: an exploration of physicians' engagement in dual
      practice in three African capital cities.
AB  - Scarce evidence exists on the features, determinants and implications of
      physicians' dual practice, especially in resource-poor settings. This study
      considered dual practice patterns in three African cities and the respective
      markets for physician services, with the objective of understanding the influence
      of local determinants on the practice. Forty-eight semi-structured qualitative
      interviews were conducted in the three cities to understand features of the
      practice and the respective markets. A survey was carried out in a sample of 331
      physicians to explore their characteristics and decisions to work in public and
      private sectors. Descriptive analysis and inferential statistics were employed to
      explore differences in physicians' engagement in dual practice across the three
      locations. Different forms of dual practice were found to exist in the three
      cities, with public physicians engaging in private practice outside but also
      inside public facilities, in regulated as well as unregulated ways. Thirty-four
      per cent of the respondents indicated that they worked in public practice only,
      and 11% that they engaged exclusively in private practice. The remaining 55%
      indicated that they engaged in some form of dual practice, 31% 'outside' public
      facilities, 8% 'inside' and 16% both 'outside' and 'inside'. Local health system
      governance and the structure of the markets for physician services were linked to
      the forms of dual practice found in each location, and to their prevalence. Our
      analysis suggests that physicians' decisions to engage in dual practice are
      influenced by supply and demand factors, but also by how clearly separated public
      and private markets are. Where it is possible to provide little-regulated
      services within public infrastructure, less incentive seems to exist to engage in
      the formal private sector, with equity and efficiency implications for service
      provision. The study shows the value of analysing health markets to understand
      physicians' engagement in professional activities, and contributes to an evidence
      base for its regulation. 

PMID- 24077881
TI  - Arbuscular mycorrhizal fungi: potential biocontrol agents against the damaging
      root hemiparasite Pedicularis kansuensis?
AB  - Spatial expansion of root hemiparasitic Pedicularis kansuensis in Bayanbulak
      Grassland of Xinjiang Uygur Autonomous Region (China) has caused great loss of
      herbage yield and has threatened the local livestock industry. Current management
      practices using manual eradication and chemical control have been proved
      problematic. Arbuscular mycorrhizal (AM) fungi have been suggested to be
      potential biocontrol agents against a number of plant pests, but experimental
      evidence is lacking against weedy P. kansuensis. In this study, we tested the
      hypothesis that inoculation with AM fungi will cause growth depression in P.
      kansuensis and reduce its damage to host plants. Based on the confirmation of AM
      status and host community of the hemiparasite in the field, a pot cultivation
      experiment was conducted to test the influence of an AM fungus (Glomus mosseae)
      on growth of P. kansuensis and the parasitized host (Elymus nutans). AM
      colonization was observed in roots of P. kansuensis, but the levels were much
      lower than those of its adjacent host species. A negative correlation between AM
      levels and the numbers of haustoria was detected for the field samples of the
      hemiparasite. Strong suppression of haustorium formation, a significant reduction
      in plant dry weight (DW), as well as marked reduction in the survival rate of P.
      kansuensis after inoculation with AM fungi was observed. In contrast, inoculation
      with G. mosseae increased root DW and whole plant DW of parasitized host plants.
      Our findings demonstrated significantly repressive effects of AM fungi on growth
      performance of P. kansuensis with and without the presence of a host. The
      potential of AM fungi as biocontrol agents against the damaging hemiparasite was
      confirmed.

PMID- 24077882
TI  - Morphological and functional effects on cardiac tissue induced by moderate zinc
      deficiency during prenatal and postnatal life in male and female rats.
AB  - The aim of this study was to evaluate whether moderate zinc restriction in rats
      throughout fetal life, lactation, and/or postweaning growth results in early
      changes in cardiac morphology predisposing the onset of cardiac dysfunction in
      adult life as well as sex-related differences in the adaptation to this
      nutritional injury. Female Wistar rats received low or control zinc diets from
      the beginning of pregnancy up to offspring weaning. After being weaned, offspring
      were fed either a low or control zinc diet until 81 days. Systolic blood pressure
      was measured. Echocardiographic and electrocardiographic examinations,
      morphological experiments, and apoptosis by TUNEL assay were performed in the
      left ventricle. In the early stages, zinc-deficient male and female offspring
      showed an increase in cardiomyocyte diameter, probably associated with an
      increase in cardiac apoptotic cells, but smaller myocyte diameters in adulthood.
      In adult males, this nutritional injury induced decreased contractility and
      dilatation of the left ventricle, not allowing the heart to compensate the higher
      levels of blood pressure, and hypertrophic remodeling of coronary arteries
      associated with increased blood pressure. Adequate zinc intake during postweaning
      life did not overcome blood pressure levels but reversed some of the detrimental
      effects of earlier zinc deficiency in cardiac morphology and function. Females
      were less sensitive to this deficiency, exhibiting normal levels of blood
      pressure and no structural or functional heart alterations in adult life. The
      present study demonstrates that the effects of zinc deficiency on blood pressure,
      cardiac morphology, and function differ between sexes, with males more
      predisposed to develop cardiovascular diseases in adulthood.

PMID- 24077884
TI  - Computational study of culture conditions and nutrient supply  in a hollow
      membrane sheet bioreactor for large-scale bone tissue  engineering.
AB  - Successful bone tissue culture in a large implant is still a challenge. We have
      previously developed a porous hollow membrane sheet (HMSh) for tissue engineering
      applications (Afra Hadjizadeh and Davod Mohebbi-Kalhori, J Biomed. Mater. Res.
      Part A [2]). This study aims to investigate culture conditions and nutrient
      supply in a bioreactor made of HMSh. For this purpose, hydrodynamic and mass
      transport behavior in the newly proposed hollow membrane sheet bioreactor
      including a lumen region and porous membrane (scaffold) for supporting and
      feeding cells with a grooved section for accommodating gel-cell matrix was
      numerically studied. A finite element method was used for solving the governing
      equations in both homogenous and porous media. Furthermore, the cell resistance
      and waste production have been included in a 3D mathematical model. The
      influences of different bioreactor design parameters and the scaffold properties
      which determine the HMSh bioreactor performance and various operating conditions
      were discussed in detail. The obtained results illustrated that the novel
      scaffold can be employed in the large-scale applications in bone tissue
      engineering.

PMID- 24077883
TI  - Systems proteomics of cardiac chromatin identifies nucleolin as a regulator of
      growth and cellular plasticity in cardiomyocytes.
AB  - Myocyte hypertrophy antecedent to heart failure involves changes in global gene
      expression, although the preceding mechanisms to coordinate DNA accessibility on
      a genomic scale are unknown. Chromatin-associated proteins alter chromatin
      structure by changing their association with DNA, thereby altering the gene
      expression profile. Little is known about the global changes in chromatin
      subproteomes that accompany heart failure, and the mechanisms by which these
      proteins alter chromatin structure. The present study tests the fundamental
      hypothesis that cardiac growth and plasticity in the setting of disease
      recapitulates conserved developmental chromatin remodeling events. We used
      quantitative proteomics to identify chromatin-associated proteins extracted via
      detergent and to quantify changes in their abundance during disease. Our study
      identified 321 proteins in this subproteome, demonstrating it to have modest
      conservation (37%) with that revealed using strong acid. Of these proteins, 176
      exhibited altered expression during cardiac hypertrophy and failure; we conducted
      extensive functional characterization of one of these proteins, Nucleolin.
      Morpholino-based knockdown of nucleolin nearly abolished protein expression but
      surprisingly had little impact on gross morphological development. However,
      hearts of fish lacking Nucleolin displayed severe developmental impairment,
      abnormal chamber patterning and functional deficits, ostensibly due to defects in
      cardiac looping and myocyte differentiation. The mechanisms underlying these
      defects involve perturbed bone morphogenetic protein 4 expression, decreased rRNA
      transcription, and a shift to more heterochromatic chromatin. This study reports
      the quantitative analysis of a new chromatin subproteome in the normal and
      diseased mouse heart. Validation studies in the complementary model system of
      zebrafish examine the role of Nucleolin to orchestrate genomic reprogramming
      events shared between development and disease.

PMID- 24077885
TI  - An approximation of the Cioslowski-Mixon bond order indexes using the AlteQ
      approach.
AB  - Fast and reliable prediction of bond orders in organic systems based upon
      experimentally measured quantities can be performed using electron density
      features at bond critical points (J Am Chem Soc 105:5061-5068, 1983; J Phys Org
      Chem 16:133-141, 2003; Acta Cryst B 61:418-428, 2005; Acta Cryst B 63:142-150,
      2007). These features are outcomes of low-temperature high-resolution X-ray
      diffraction experiments. However, a time-consuming procedure of gaining these
      quantities makes the prediction limited. In the present work we have employed an
      empirical approach AlteQ (J Comput Aided Mol Des 22:489-505, 2008) for evaluation
      of electron density properties. This approach uses a simple exponential function
      derived from comparison of electron density, gained from high-resolution X-ray
      crystallography, and distance to atomic nucleus what allows calculating density
      distribution in time-saving manner and gives results which are very close to
      experimental ones. As input data AlteQ accepts atomic coordinates of isolated
      molecules or molecular ensembles (for instance, protein-protein complexes or
      complexes of small molecules with proteins, etc.). Using AlteQ characteristics we
      have developed regression models predicting Cioslowski-Mixon bond order (CMBO)
      indexes (J Am Chem Soc 113(42):4142-4145, 1991). The models are characterized by
      high correlation coefficients lying in the range from 0.844 to 0.988 dependently
      on the type of covalent bond, thereby providing a bonding quantification that is
      in reasonable agreement with that obtained by orbital theory. Comparative
      analysis of CMBOs approximated using topological properties of AlteQ and
      experimental electron densities has shown that the models can be used for fast
      determination of bond orders directly from X-ray crystallography data and
      confirmed that AlteQ characteristics can replace experimental ones with
      satisfactory extent of accuracy.

PMID- 24077886
TI  - Favourable results of a new intraoperative and postoperative filtered autologous
      blood re-transfusion system in total hip arthroplasty: a randomised controlled
      trial.
AB  - PURPOSE: A new intraoperative filtered salvaged blood re-transfusion system has
      been developed for primary total hip arthroplasty (THA) that filters and re
      transfuses the blood that is lost during THA. This system is intended to increase
      postoperative haemoglobin (Hb) levels, reduce perioperative net blood loss and
      reduce the need for allogeneic transfusions. It supposedly does not have the
      disadvantages of intraoperative cell-washing/separating re-transfusion systems,
      such as extensive procedure, high costs and need for specialised personnel. To re
      transfuse as much as blood as possible, postoperatively drained blood was also re
      transfused. METHODS: A randomised, controlled, blinded, single-centre trial was
      conducted in which 118 THA patients were randomised to an intraoperative
      autologous blood re-transfusion (ABT) filter system combined with a postoperative
      ABT filter unit or high-vacuum closed-suction drainage. RESULTS: On average, 577
      ml of blood was re-transfused in the ABT group: 323 ml collected intraoperatively
      and 254 ml collected postoperatively. Hb level was higher in the ABT vs the high
      vacuum drainage group: 11.4 vs. 10.8 g/dl, p = 0.02 on day one (primary endpoint)
      and 11.0 vs. 10.4 g/dl, p = 0.007 on day three. Total blood loss was less in the
      autotransfusion group: 1472 vs. 1678 ml, p = 0.03. Allogeneic transfusions were
      needed in 3.6 % of patients in the ABT group and 6.5 % in the drainage group, p =
      0.68. CONCLUSION: The use of a new intraoperative ABT filter system combined with
      a postoperative ABT unit resulted in higher postoperative Hb levels and less
      total blood loss compared with a high-vacuum drain following THA.

PMID- 24077887
TI  - The incidence of implant fractures after total hip arthroplasty.
AB  - PURPOSE: Implant fractures after total hip arthroplasty (THA) are considered as
      rare in clinical practice. Nevertheless they are relevant complications for
      patients, physicians, and the public health system leading to high socioeconomic
      burdens. The aim of this study was to assess the incidence of fractures after
      THAs in a comparative analysis of clinical studies and worldwide arthroplasty
      register datasets. METHODS: We calculated the pooled incidence of revision
      operations after fractures of THAs in a comparison of clinical studies published
      in Medline-listed journals and annual reports of worldwide arthroplasty registers
      in a structured literature analysis based on a standardised methodology. RESULTS:
      Included clinical studies (sample-based datasets) were mono-centre trials
      comprising a cumulative number of approximately 70,000 primary implantations
      whereas worldwide national arthroplasty register datasets referred to 733,000
      primary implantations, i.e. approximately ten times as many as sample-based
      datasets. In general, sample-based datasets presented higher revision rates than
      register datasets with a maximum deviation of a 14.5 ratio for ceramic heads,
      respectively. The incidence of implant fractures in total hip arthroplasty in
      pooled worldwide arthroplasty register datasets is 304 fractures per 100,000
      implants. In other words, one out of 323 patients has to undergo revision surgery
      due to an implant fracture after THA in their lifetime. CONCLUSIONS: Implant
      fractures in total hip arthroplasty occur in a relevant number of patients. The
      authors believe that comprehensive arthroplasty register datasets allow more
      general evaluations and conclusions on that topic in contrast to clinical
      studies.

PMID- 24077888
TI  - Identification and diversity of functional centromere satellites in the wild rice
      species Oryza brachyantha.
AB  - The centromere is a key chromosomal component for sister chromatid cohesion and
      is the site for kinetochore assembly and spindle fiber attachment, allowing each
      sister chromatid to faithfully segregate to each daughter cell during cell
      division. It is not clear what types of sequences act as functional centromeres
      and how centromere sequences are organized in Oryza brachyantha, an FF genome
      species. In this study, we found that the three classes of centromere-specific
      CentO-F satellites (CentO-F1, CentO-F2, and CentOF3) in O. brachyantha share no
      homology with the CentO satellites in Oryza sativa. The three classes of CentO-F
      satellites are all located within the chromosomal regions to which the spindle
      fibers attach and are characterized by megabase tandem arrays that are flanked by
      centromere-specific retrotransposons, CRR-F, in the O. brachyantha centromeres.
      Although these CentO-F satellites are quantitatively variable among 12 O.
      brachyantha centromeres, immunostaining with an antibody specific to CENH3
      indicates that they are colocated with CENH3 in functional centromere regions.
      Our results demonstrate that the three classes of CentO-F satellites may be the
      major components of functional centromeres in O. brachyantha.

PMID- 24077890
TI  - Pathology of clinical and preclinical Alzheimer's disease.
AB  - Alzheimer's disease (AD) is characterized neuropathologically by the presence of
      amyloid plaques, neuritic plaques, and neurofibrillary tangles (NFTs). These
      lesions occur not only in demented individuals with AD but also in non-demented
      persons. In non-demented individuals, amyloid and neuritic plaques are usually
      accompanied with NFTs and are considered to represent asymptomatic or preclinical
      AD (pre-AD) pathology. Here, we defined and characterized neuropathological
      differences between clinical AD, non-demented pre-AD, and non-AD control cases.
      Our results show that clinical AD may be defined as cases exhibiting late stages
      of NFT, amyloid, and neuritic plaque pathology. This is in contrast to the
      neuropathological changes characteristic of pre-AD, which display early stages of
      these lesions. Both AD and pre-AD cases often exhibit cerebral amyloid angiopathy
      (CAA) and granulovacuolar degeneration (GVD), and when they do, these AD-related
      pathologies were at early stages in pre-AD cases and at late stages in
      symptomatic AD. Importantly, NFTs, GVD, and CAA were also observed in non-AD
      cases, i.e., in cases without amyloid plaque pathology. Moreover, soluble and
      dispersible, high-molecular-weight amyloid beta-protein (Abeta) aggregates
      detected by blue-native polyacrylamide gel electrophoresis were elevated in
      clinical AD compared to that in pre-AD and non-AD cases. Detection of NFTs, GVD,
      and CAA in cases without amyloid plaques, presently classified as non-AD, is
      consistent with the idea that NFTs, GVD, and CAA may precede amyloid plaque
      pathology and may represent a pre-amyloid plaque stage of pre-AD not yet
      considered in the current recommendations for the neuropathological diagnosis of
      AD. Our finding of early stages of AD-related NFT, amyloid, and GVD pathology
      provides a more clear definition of pre-AD cases that is in contrast to the
      changes in clinical AD, which is characterized by late stages of these AD-related
      pathologies. The observed elevation of soluble/dispersible Abeta aggregates from
      pre-AD compared to that in AD cases suggests that, in addition to more widespread
      AD-related pathologies, soluble/dispersible Abeta aggregates in the neuropil play
      a role in the conversion of pre-AD to clinical AD.

PMID- 24077889
TI  - Depressive syndromes in neurological disorders.
AB  - Depressive syndromes represent a common and often characteristic feature in a
      number of neurological disorders. One prominent example is the development of
      post-stroke depression, which can be observed in more than one-third of stroke
      survivors in the aftermath of an ischemic stroke. Thus, post-stroke depression
      represents one of the most prevalent, disabling, and potentially devastating
      psychiatric post-stroke complications. On the other hand, depressive syndromes
      may also be considered as a risk factor for certain neurological disorders, as
      recently revealed by a meta-analysis of prospective cohort studies, which
      demonstrated an increased risk for ischemic events in depressed patients.
      Moreover, depressive syndromes represent common comorbidities in a number of
      other neurological disorders such as Parkinson's disease, multiple sclerosis, or
      epilepsy, in which depression has a strong impact on both quality of life and
      outcome of the primary neurological disorder.

PMID- 24077891
TI  - Effect of protein aggregation on the spectroscopic properties  and excited state
      kinetics of the LHCII pigment-protein  complex from green plants.
AB  - Steady-state and time-resolved absorption and fluorescence spectroscopic
      experiments have been carried out at room and cryogenic temperatures on
      aggregated and unaggregated monomeric and trimeric LHCII complexes isolated from
      spinach chloroplasts. Protein aggregation has been hypothesized to be one of the
      mechanistic factors controlling the dissipation of excess photo-excited state
      energy of chlorophyll during the process known as nonphotochemical quenching. The
      data obtained from the present experiments reveal the role of protein aggregation
      on the spectroscopic properties and dynamics of energy transfer and excited state
      deactivation of the protein-bound chlorophyll and carotenoid pigments.

PMID- 24077893
TI  - High-efficiency system for construction and evaluation of customized TALENs for
      silkworm genome editing.
AB  - Transcription activator-like effector nuclease (TALEN) possesses the
      characteristics of ease design and precise DNA targeting. In the silkworm Bombyx
      mori, TALEN has been successfully used to knockout an endogenous Bombyx gene, and
      shown the huge potential in functional genes research and improvement of the
      economical characteristics of silkworm. Thus, there is an urgent need to develop
      an applicable system that permits the efficient construction of customized TALEN
      with high activity that could efficiently induce the hereditable mutagenesis in
      the silkworm. In this study, we constructed an efficient assembly and evaluation
      system of the customized TALEN especiallly for silkworm genome editing by
      combination of a modified Golden Gate ligation strategy, a luciferase (LUC)
      reporter system in insect cell culture for binding activity and a surveyor
      nuclease assay system in silkworm embryos for cleavage efficiency. We showed the
      reliability of this system by assembling a pair of TALENs targeting a silkworm
      genome locus and assaying their binding and cleavage activities. The assembly
      strategy was convenient and efficient which allows the rapid construction of
      customized TALEN in less than 1 week, and the evaluation system was reliable and
      necessary for screening of the customized TALEN pair with high binding and
      cleavage activities. The results showed this system is a reliable and efficient
      tool for the construction of customized TALEN with high activity for gene
      targeting of silkworm, and will contribute to the wide application of TALEN
      technology in the functional gene research of silkworm.

PMID- 24077892
TI  - The nonheme iron in photosystem II.
AB  - Photosystem II (PSII), the light-driven water:plastoquinone (PQ) oxidoreductase
      of oxygenic photosynthesis, contains a nonheme iron (NHI) at its electron
      acceptor side. The NHI is situated between the two PQs QA and QB that serve as
      one-electron transmitter and substrate of the reductase part of PSII,
      respectively. Among the ligands of the NHI is a (bi)carbonate originating from
      CO2, the substrate of the dark reactions of oxygenic photosynthesis. Based on
      recent advances in the crystallography of PSII, we review the structure of the
      NHI in PSII and discuss ideas concerning its function and the role of bicarbonate
      along with a comparison to the reaction center of purple bacteria and other
      enzymes containing a mononuclear NHI site.

PMID- 24077894
TI  - Validation of a Chinese version of the Frenchay Activities Index in patients with
      traumatic limb injury.
AB  - PURPOSE: The Frenchay Activities Index (FAI) is a frequently used measure that
      assesses instrumental activities of daily living (IADL). However, the measurement
      properties of the FAI are largely unknown for patients with traumatic limb
      injuries. The purpose of this study was to examine the measurement properties of
      a Chinese version of the FAI, including score distribution, internal consistency,
      construct validity, predictive validity, and responsiveness in patients with
      traumatic limb injuries. METHODS: We performed a secondary data analysis,
      primarily using non-parametric item response theory, on a data set. The FAI and
      the World Health Organization Quality of Life Assessment (WHOQOL-BREF) were
      administered via telephone interview to a cohort of patients at 3, 6, and 12
      months after injury. Totals of 342 patients' data (at 3 months after injury),
      1,010 patients' data (6 months), and 987 patients' data (12 months) were
      available for analysis. RESULTS: After the deletion of 5 items (i.e., travel
      outings, gardening, household/car maintenance, reading books, and gainful work),
      the 10-item revised FAI (R-FAI) formed a unidimensional construct. The R-FAI
      exhibited a unidimensional construct at each of the 3 time points. The R-FAI had
      sufficient score distribution, internal consistency, predictive validity, and
      responsiveness in patients with limb injuries. CONCLUSIONS: Our results support
      the conclusion that the R-FAI has satisfactory measurement properties. The R-FAI
      is useful for assessing IADL in patients with limb injuries.

PMID- 24077895
TI  - Endothelial signaling and the molecular basis of arteriovenous malformation.
AB  - Arteriovenous malformations occur when abnormalities of vascular patterning
      result in the flow of blood from arteries to veins without an intervening
      capillary bed. Recent work has revealed the importance of the Notch and TGF-beta
      signaling pathways in vascular patterning. Specifically, Notch signaling has an
      increasingly apparent role in arterial specification and suppression of
      branching, whereas TGF-beta is implicated in vascular smooth muscle development
      and remodeling under angiogenic stimuli. These physiologic roles, consequently,
      have implicated both pathways in the pathogenesis of arteriovenous malformation.
      In this review, we summarize the studies of endothelial signaling that contribute
      to arteriovenous malformation and the roles of genes implicated in their
      pathogenesis. We further discuss how endothelial signaling may contribute to
      vascular smooth muscle development and how knowledge of signaling pathways may
      provide us targets for medical therapy in these vascular lesions.

PMID- 24077896
TI  - Obesity, health-care utilization, and health-related quality of life after
      fracture in postmenopausal women: Global Longitudinal Study of Osteoporosis in
      Women (GLOW).
AB  - Fractures may be associated with higher morbidity in obese postmenopausal women
      than in nonobese women. We compared health-care utilization, functional status,
      and health-related quality of life (HRQL) in obese, nonobese, and underweight
      women with fractures. Information from the GLOW study, started in 2006, was
      collected at baseline and at 1, 2, and 3 years. In this subanalysis, self
      reported incident clinical fractures, health-care utilization, HRQL, and
      functional status were recorded and examined. Women in GLOW (n = 60,393) were
      aged >=55 years, from 723 physician practices at 17 sites in 10 countries.
      Complete data for fracture and body mass index were available for 90 underweight,
      3,270 nonobese, and 941 obese women with one or more incident clinical fractures
      during the 3-year follow-up. The median hospital length of stay, adjusted for
      age, comorbidities, and fracture type, was significantly greater in obese than
      nonobese women (6 vs. 5 days, p = 0.017). Physical function and vitality score
      were significantly worse in obese than in nonobese women, both before and after
      fracture; but changes after fracture were similar across groups. Use of
      antiosteoporosis medication was significantly lower in obese than in nonobese or
      underweight women. In conclusion, obese women with fracture undergo a longer
      period of hospitalization for treatment and have poorer functional status and
      HRQL than nonobese women. Whether these differences translate into higher
      economic costs and adverse effects on longer-term outcomes remains to be
      established.

PMID- 24077897
TI  - Anterior pedicle screw fixation of C2: an anatomic analysis of axis morphology
      and simulated surgical fixation.
AB  - STUDY DESIGN: Human cadaveric study measuring the morphology of C2 vertebra,
      description of anterior placement of pedicle screw with post-fixation computed
      tomography (CT) analysis. OBJECTIVE: To assess the potential feasibility and
      safety anterior placement of C2 pedicle screws. SUMMARY OF BACKGROUND DATA:
      Posterior pedicle screw fixation has become an established technique for upper
      cervical reconstruction. To our knowledge few reports in the previous literature
      have described the placement of or anatomy related to anteriorly approach C2
      pedicle screws. METHODS: The morphology of 60 human C2 vertebrae was measured
      directly to assess the size, position, and relative approach angle of the
      pedicles from an anterior perspective. In an additional 20 cadaveric cervical
      spines, bilateral 3.5 mm titanium C2 pedicle screws were placed and analyzed for
      pedicle morphology and placement accuracy with thin cut, 1 mm axial CT. RESULTS:
      The mean C2 pedicle width measured directly and by CT scan was 7.8 and 6.6 mm,
      and the average length of the right and left pedicle was 26.4 and 25 mm,
      respectively. The mean transverse angle (alpha) was 17.6 degrees  and 21.4
      degrees , whereas declination angle (beta) anterior to posterior was 13.8 degrees
      and 10.6 degrees , respectively. CONCLUSIONS: Quantitative data regarding C2
      pedicle shape and location with respect to the anterior placement of pedicle
      screws have not been previously reported. This study indicates that anterior
      placement of 3.5 mm C2 pedicle screws through a transoral approach may be both
      feasible and safe and also provides an important anatomic analysis that may guide
      clinical application.

PMID- 24077898
TI  - Masters of their Conditions III: Clinical applications of theater anthropology in
      cultural psychiatry.
AB  - Body learning gives actors basic structures and references that enable them to
      codify their actions in a script or score. With this score, acquired through
      training, performing and transmitting, actors who work with theater anthropology
      methodology offer strategies and tools that healers can use with their patients.
      This actor's score has inspired a mode of working with patients both to
      understand the case history and guide the course of therapy. In this approach,
      patients are like authors who want to act out their dramaturgy, but who need a
      director-healer to organize the story and help them build their healing process.
      Together, patient and therapist work on stage to advance the treatment, at the
      same time enhancing their strategies and methods for collaboration. 

PMID- 24077899
TI  - Noninvasive evaluation of cardiac autonomic modulation in children with primary
      Raynaud's phenomenon: a controlled study.
AB  - This study aimed to objectively evaluate autonomic nervous function in children
      with primary Raynaud's phenomenon (PRP). Thirty-two children with PRP and 30
      healthy subjects were included in the study. We analyzed heart rate variability
      (HRV) in the time domain by the following six standard time-domain measures:
      standard deviation of all normal R-R intervals during 24 h (SDNN), standard
      deviation of all normal R-R intervals for all 5-min segments (SDNNi), standard
      deviation of the average normal R-R intervals for all 5-min segments (SDANN),
      root mean square of the successive normal R-R interval difference, percentage of
      successive normal R-R intervals longer than 50 ms, and triangular index (integral
      of the density distribution of NN intervals divided by the maximum of the density
      distribution). The mean heart rate throughout 24 h was significantly higher in
      the PRP group than in the control group (p = 0.001). Although heart rate during
      the activity period was not significantly different from that during the night
      period, it was higher in the PRP group than in the control group (p = 0.002). In
      children with PRP, HRV analysis showed significantly lower values of SDNN (p =
      0.01), SDNNi (p = 0.005), SDANN (p = 0.02), and HRV triangular index (p = 0.02)
      compared with the control group. HRV analysis for sympathovagal balance
      demonstrated a preponderance for the sympathetic component in patients with PRP.
      We conclude that all time-domain parameters evaluated in HRV analysis are
      significantly lower in children with PRP than in healthy subjects.

PMID- 24077900
TI  - Experiences of gout-related disability from the patients' perspective: a mixed
      methods study.
AB  - Disability is a common problem in patients with gout. Recently, the Health
      Assessment Questionnaire Disability Index (HAQ-DI) was recommended for assessing
      patient reported activity limitations in gout. However, few studies have explored
      experiences and issues of disability from the perspective of gout patients
      themselves. The objectives of this study were to explore disability issues in
      patients with gout and to examine the content validity of the HAQ-DI in this
      patient group. Two studies were performed: a semi-structured interview study with
      seven male gout patients and a cross-sectional survey study among 34 other
      patients with gout. In both studies, specific examples of activity limitations
      were elicited using open-ended methods. The survey study additionally aimed to
      quantify the relevance of the activities listed in the HAQ-DI. Most patients
      experienced several gout attacks in the previous year. Limitations were reported
      to occur during a flare, but patients were generally not limited between attacks.
      During an attack, patients mainly experienced limitations related to mobility,
      especially walking and climbing stairs. Patients also mentioned limitations in
      activities related to domestic life, such as gardening and doing housework.
      Limitations related to self-care or activities requiring the use of the upper
      extremities were rarely mentioned. Corresponding HAQ-DI items were skewed towards
      very low disability scores over the past week. Assessments of gout-related
      disability should particularly focus on mobility and lower extremity functioning
      and should consider the intermittent nature of the disease. The HAQ-DI may not
      adequately meet these requirements, suggesting the need to explore other measures
      of gout-related disability

PMID- 24077901
TI  - Rotational thromboelastometry (ROTEM) in Behcet's disease.

PMID- 24077902
TI  - Gout: from international guidelines to current practice. Results from a physician
      questionnaire.

PMID- 24077903
TI  - In Defence of Professional Judgement.
AB  - A judgement is an assertion made with evidence or good reason in a context of
      uncertainty. In psychiatry the uncertainty is inherent in the professional
      context, and the evidence derives from the academic literature and scientific
      studies as they are applied to a specific patient. The nature of the uncertainty
      and the factors which should inform professional judgement are explored.
      Professional judgement is currently facing two serious challenges: an obsession
      with numbers, which comes from within medicine, and the 'patient choice' agenda,
      which is politically inspired and comes from outside medicine. This paper strives
      to defend professional judgement in the clinic against both challenges.

PMID- 24077904
TI  - No Evidence of Significant Levels of Toxigenic V. cholerae O1 in the Haitian
      Aquatic Environment During the 2012 Rainy Season.
AB  - BACKGROUND: On October 21, 2010, Haiti was struck by a cholera epidemic for the
      first time in over a century. Epidemiological and molecular genetic data have
      clearly demonstrated that the bacterium was imported. Nevertheless, the
      persistence of the epidemic for more than two years, the high incidence rates in
      some coastal areas and the seasonal exacerbations of the epidemic during the
      rainy seasons have prompted us to examine the levels of toxigenic Vibrio cholerae
      in the Haitian aquatic environment. METHODS: In July 2012, during the warm and
      rainy season, 36 aquatic stations were sampled to search for toxigenic V.
      cholerae. These stations included fresh, brackish and saline surface waters as
      well as waste water; the sampling sites were located in both rural and urban
      areas (around Port-au-Prince and Gonaives) located in the West and Artibonite
      Departments. V. cholerae bacteria were detected in enrichment cultures of water
      samples (sample volumes included 1 L, 100 mL, 10 mL, 1 mL, 0.1 mL, 0.01 mL and
      0.001 mL depending on the context). Detection methods included both culture on
      selective agar (for strain isolation) and PCR assays targeting the genes ompW (V.
      cholerae species), O1-rfb and O139-rfb (O1 and O139 V. cholerae serogroups,
      respectively), and the cholera toxin gene ctxA, which is present exclusively in
      toxigenic cholera strains. RESULTS: A total of 411 culturable V. cholerae
      isolates from 29 stations were obtained via selective culture; however, only one
      of these isolates displayed a late positive reaction with polyvalent anti-O1
      serum. Positive V. cholerae PCR results were obtained from each of the 32 tested
      stations (a total of 77 enrichments out of 107 yielded a positive result); only
      one sample yielded a positive V. cholerae O1 PCR result. The cholera toxin gene
      ctxA was never detected via PCR with either primer pair, which includes samples
      derived from the two stations yielding positive O1 culture or positive O1 PCR
      results. Therefore, we could not demonstrate the presence of toxigenic V.
      cholerae O1 among the 36 stations sampled. This suggests that all water samples
      analyzed contained less than 10 toxigenic V. cholerae O1 bacteria per liter, a
      level 1000-fold below the dose that has been shown to provoke cholera in healthy
      adults. CONCLUSIONS: Currently, there is no evidence of a significant level of
      contamination of the aquatic environment in Haiti by the imported toxigenic V.
      cholerae O1 strain. The reemergence of cholera outbreaks in Haiti during rainy
      seasons is therefore more likely due to persisting outbreaks insufficiently
      tackled during the dry periods rather than the commonly suspected aquatic
      reservoir of toxigenic bacteria.

PMID- 24077905
TI  - Race and incarceration in an aging cohort of Vietnam veterans in treatment for
      post-traumatic stress disorder (PTSD).
AB  - Cross sectional studies have addressed the incarceration of Vietnam veterans with
      post-traumatic stress disorder (PTSD), but no studies have examined changes in
      incarceration as they age. This study examines patterns of incarceration among
      Vietnam veterans treated in specialized veterans affairs (VA) intensive PTSD
      programs over time. Data was drawn from admission data from the initial episode
      of treatment of Caucasian and African American Vietnam veterans entering VA
      specialized intensive PTSD programs between 1993 and 2011 (N = 31,707). Bivariate
      correlations and logistic regression were used to examine associations among race
      and incarceration over time and the potentially confounding influence of
      demographic and clinical covariates on this relationship. Rates of reported
      incarceration declined from 63 to 43%. Over time, African American veterans were
      34% more likely than Caucasian veterans to have a lifetime history of
      incarceration while interaction analysis showed steeper declines for Caucasians
      than African Americans. Rates of incarceration among these Vietnam veterans
      declined as they aged. Furthermore, African American veterans were substantially
      more likely than Caucasian veterans to have been incarcerated and showed less
      decline as the cohort aged. While reduced, needs for clinical PTSD services
      remain among aging combat veterans.

PMID- 24077906
TI  - Illness conceptualizations among older rural Mexican-Americans with anxiety and
      depression.
AB  - Research on barriers and utilization of mental health services in older ethnic
      minorities has been productive. However, little is known about the
      characterization and beliefs about anxiety and depression symptoms among older
      Mexican-Americans. Exploration of these conceptualizations will lead to better
      detection and provision of care to this large, yet underserved group. The present
      study used a mixed methods approach to explore conceptualizations of anxiety and
      depression in a group of rural older Mexican-Americans. Twenty-five Spanish
      speaking participants (mean age 71.2) responded to flyers that solicited
      individuals who felt "tense or depressed." Participants completed a structured
      diagnostic interview as well as self-report questionnaires about medical health,
      anxiety and depressive symptoms, and cognitive functioning. Qualitative
      interviews included questions about how participants describe, conceptualize, and
      cope with anxiety and depression symptoms. Sixty-eight percent of the sample met
      criteria for at least one anxiety or mood disorder with high comorbidity rates.
      Self-reported symptoms of depression, anxiety, and somatization were below
      clinical ranges for all participants. Medical illness, cognitive impairment, age,
      education, and acculturation were not associated with distress. Qualitative
      analyses revealed that nearly half of the terms used by the sample to describe
      distress phenomena deviated from Western labels traditionally used to indicate
      anxious and depressive symptomatology. Multiple methods of symptom endorsement
      demonstrated that older Mexican-Americans may report distress differently than
      detected by traditional self-report measures or common Western terminology.
      Understanding these additional illness conceptualizations may have implications
      for improving the detection of mental illness and increasing service use among
      this growing population.

PMID- 24077907
TI  - Which level of competence and performance is expected? A survey among European
      employers of public health professionals.
AB  - OBJECTIVES: To explore largely unknown experience and expectations of European
      employers of public health professionals with regard to competences required to
      perform in the best way for the public health. METHODS: A survey targeting
      employers in Europe was carried out September 2011-October 2012. The web-based
      questionnaire on public health competences and expected performance levels was
      returned by 63 organisations out of 109 contacted (57.8 %) as provided by Schools
      and Departments of Public Health (SDPH) in 30 European countries. RESULTS: The
      assessment of the current and desired levels of performance did not show
      significant differences between employer categories. However, current and desired
      levels across all employers differ significantly (p < 0.001), varying around a
      difference of one rank of a five-point scale. On the other hand, SDPH rank the
      exit qualifications of their graduates with one exception (presumed competences
      in preparedness for public health emergencies) higher than the current
      performance level as determined by employers, i.e. closer to their expectations.
      CONCLUSIONS: SDPH should reconsider priorities and question their estimate of
      exit qualifications in close contact with potential employers of their graduates.

PMID- 24077908
TI  - A prospective study of paediatric obsessive-compulsive symptomatology in a
      Spanish community sample.
AB  - The obsessive-compulsive manifestations course was assessed with the Leyton
      obsessional inventory-child version survey (LOI-CV) in a 3-year prospective
      study, using a non-clinical sample. From an initial sample of 1,514 school-age
      children who underwent symptoms screening for obsessive-compulsive, anxiety and
      depression, 562 subjects (risk group/without risk group) were re-assessed in the
      2nd phase and 242 subjects were monitored after 3 years. LOI-CV scores
      significantly decreased over time independently of age and gender. The
      prevalence, persistence and incidence for two levels of severity of obsessive
      compulsive manifestations ranged between 4.8-30.4%, 9.3-28.4% and 1.1-14.4%,
      respectively. 34.6-64.5% of obsessive-compulsive symptomatology was predicted by
      anxiety, depressive and obsessive-compulsive symptoms. For the obsessiveness
      (less severe form of obsessive-compulsive manifestations), the depressive
      symptoms were not predictors. Gender and socioeconomic status were not related
      with obsessive-compulsive manifestations. These data support a substantial
      continuity of the obsessive-compulsive manifestations and the existence of
      different levels of severity within the obsessive-compulsive spectrum.

PMID- 24077909
TI  - Toward the development of a supported employment program for individuals with
      high-functioning autism in Germany.
AB  - Human-human interactions are of central relevance for the success in professional
      and occupational environments, which also substantially influence quality of
      life. This is especially true in the case of individuals with high-functioning
      autism (HFA), who experience deficits in social cognition that often lead to
      social exclusion and unemployment. Despite good education and high motivation,
      individuals with HFA do not reach employment rates that are substantially higher
      than 50 %. This is an alarmingly high rate of unemployment considering that the
      United Nations have recently emphasized the inclusion of handicapped persons as a
      mandatory human right. To date, the specific needs of autistic persons with
      respect to their working environment are largely unexplored. It remains moreover
      an open question how support systems and activities, including newly developed
      communication devices for professional environments of individuals with HFA,
      should look like. The German health and social care systems are not adequately
      prepared for the proper support of this population. This leads us to suggest that
      supported employment programs should be developed for adults with HFA that
      specifically address their needs and requirements. Such programs should comprise
      (1) the adequate assessment of HFA, including a neuropsychological profile and an
      individual matching of persons' preferences with requirements of the working
      place, (2) on-the-job coaching activities that include systematic communication
      and interaction training, and (3) instruction of non-autistic peers, including
      colleagues and supervisors, about weaknesses and strengths of HFA.

PMID- 24077910
TI  - Adult attention-deficit/hyperactivity disorder in major depressed  and bipolar
      subjects: role of personality traits and clinical  implications.
AB  - A significant comorbidity between attention-deficit/hyperactivity disorder (ADHD)
      and affective disorders has been consistently reported in adults. Less data
      regarding the role of personality traits and the influence of ADHD co-occurrence
      on clinical characteristics and outcome of mood disorders are currently
      available. One hundred and six remitted major depressed, 102 euthymic bipolar
      subjects, and 120 healthy controls, homogeneous with respect to demographic
      characteristics, were included in the study. ADHD diagnosis was based on DSM-IV
      TR criteria. Childhood and adult ADHD features were measured with the Wender Utah
      Rating Scale, the Adult ADHD Self-rating Scale, and the Brown Attention-Deficit
      Disorder Scale. The Revised NEO Personality Inventory was also administered to
      the clinical groups, in order to investigate personality dimensions. The
      occurrence of adult ADHD in subjects with bipolar disorders (BD) or major
      depressive disorder (MDD) was 15.7 and 7.5 %, respectively, compared to 3.3 % in
      healthy controls (HC). Significant associations (p < .001) between personality
      traits (neuroticism, conscientiousness, and extraversion) and ADHD features were
      observed. Logistic regression analysis of all clinical subjects (n = 208) showed
      that those with lower levels of neuroticism (OR = 1.031; p = .025) had a lower
      frequency of ADHD comorbidity. The present study emphasizes the close
      relationship between affective disorders, especially BD, and ADHD in adults. Our
      findings support the need to assess subjects with mood disorders in the clinical
      setting for possible coexisting ADHD and to further investigate personality
      traits to better understand the etiology of affective disorders and ADHD co
      occurrence.

PMID- 24077911
TI  - Information density and dependency length as complementary cognitive models.
AB  - Certain English constructions permit two syntactic alternations. (1) a. I looked
      up the number. b. I looked the number up. (2) a. He is often at the office. b. He
      often is at the office. This study investigates the relationship between
      syntactic alternations and processing difficulty. What cognitive mechanisms are
      responsible for our attraction to some alternations and our aversion to
      others?This article reviews three psycholinguistic models of the relationship
      between syntactic alternations and processing: Maximum Per Word Surprisal
      (building on the ideas of Hale, in Proceedings of the 2nd Meeting of the North
      American chapter of the association for computational linguistics. Association
      for Computational Linguistics, Pittsburgh, PA, pp 159-166, 2001), Uniform
      Information Density (UID) (Levy and Jaeger in Adv Neural Inf Process Syst 19:849
      856, 2007; inter alia), and Dependency Length Minimization (DLM) (Gildea and
      Temperley in Cognit Sci 34:286-310, 2010). Each theory makes predictions about
      which alternations native speakers should favor. Subjects were recruited using
      Amazon Mechanical Turk and asked to judge which of two competing syntactic
      alternations sounded more natural. Logistic regression analysis on the resulting
      data suggests that both UID and DLM are powerful predictors of human preferences.
      We conclude that alternations that approach uniform information density and
      minimize dependency length are easier to process than those that do not. 

PMID- 24077912
TI  - The Human Gene Mutation Database: building a comprehensive mutation repository
      for clinical and molecular genetics, diagnostic testing and personalized genomic
      medicine.
AB  - The Human Gene Mutation Database (HGMD(r)) is a comprehensive collection of
      germline mutations in nuclear genes that underlie, or are associated with, human
      inherited disease. By June 2013, the database contained over 141,000 different
      lesions detected in over 5,700 different genes, with new mutation entries
      currently accumulating at a rate exceeding 10,000 per annum. HGMD was originally
      established in 1996 for the scientific study of mutational mechanisms in human
      genes. However, it has since acquired a much broader utility as a central unified
      disease-oriented mutation repository utilized by human molecular geneticists,
      genome scientists, molecular biologists, clinicians and genetic counsellors as
      well as by those specializing in biopharmaceuticals, bioinformatics and
      personalized genomics. The public version of HGMD (http://www.hgmd.org) is freely
      available to registered users from academic institutions/non-profit organizations
      whilst the subscription version (HGMD Professional) is available to academic,
      clinical and commercial users under license via BIOBASE GmbH.

PMID- 24077913
TI  - Anti-TNF therapy in patients with HBV infection--analysis of 87 patients with
      inflammatory arthritis.
AB  - This study aims to investigate the incidence of hepatitis B virus (HBV)
      reactivation in inflammatory arthritis (IA) patients with HBV infection using
      anti-tumor necrosis factor (TNF) agents and evaluate the efficacy of antiviral
      therapy in reducing the risk of viral reactivation in chronic HBV infection. IA
      patients using anti-TNF agents from six centers were enrolled. Their HBV
      infection conditions and ALT and HBV-DNA levels were monitored periodically.
      Among the six chronic hepatitis B patients, HBV reactivation was found in two
      patients without antivirus prophylaxis and no viral replication was detected in
      the other four patients with antivirus prophylaxis. In the 31 inactive carriers,
      the increase of viral load was detected in 6 of 22 (27.3 %) patients without
      antiviral prophylaxis, and there was no viral reactivation in the other 9
      patients with antiviral prophylaxis. HBV reactivation was not found in the 50
      patients with resolved HBV infection. It is suggested that anti-TNF therapy might
      increase the risk of HBV reactivation in patients with chronic HBV infection, and
      antiviral prophylaxis could effectively decrease the risk. Anti-TNF agents seem
      to be safe in patients with resolved HBV infection.

PMID- 24077915
TI  - Another surprise from Metformin: novel mechanism of action via K-Ras influences
      endometrial cancer response to therapy.
AB  - Metformin is an oral biguanide commonly used for the treatment of type II
      diabetes and has recently been demonstrated to possess antiproliferative
      properties that can be exploited for the prevention and treatment of a variety of
      cancers. The mechanisms underlying this effect have not been fully elucidated.
      Using both in vitro and in vivo models, we examined the effects of metformin on
      endometrial tumors with defined aberrations in the PI3K/PTEN/mTOR and MAPK
      signaling pathways to understand metformin mechanism of action and identify
      clinically useful predictors of response to this agent. In vitro assays of
      proliferation, cytotoxicity, and apoptosis were used to quantify the effects of
      metformin on endometrial cancer cell lines with mutations in the PI3K/PTEN/mTOR
      and MAPK signaling pathways. The in vivo effects of oral metformin on tumor
      progression were further examined using xenograft mouse models of endometrial
      cancer. K-Ras localization was analyzed by confocal microscopy using GFP-labeled
      oncogenic K-Ras and by immunoblot following subcellular fractionation. Metformin
      inhibited cell proliferation, induced apoptosis, and decreased tumor growth in
      preclinical endometrial cancer models, with the greatest response observed in
      cells harboring activating mutations in K-Ras. Furthermore, metformin displaces
      constitutively active K-Ras from the cell membrane, causing uncoupling of the
      MAPK signaling pathway. These studies provide a rationale for clinical trials
      using metformin in combination with PI3K-targeted agents for tumors harboring
      activating K-Ras mutations, and reveal a novel mechanism of action for metformin.

PMID- 24077916
TI  - Safety and efficacy of neratinib in combination with weekly paclitaxel and
      trastuzumab in women with metastatic HER2-positive breast cancer: an NSABP
      Foundation Research Program phase I study.
AB  - PURPOSE: Neratinib is an oral, small-molecule inhibitor that irreversibly binds
      to pan-HER (ErbB) receptor tyrosine kinases. Studies suggest that dual anti-HER
      therapies utilized in breast cancer patients are more efficacious than single
      agents in both the metastatic and neoadjuvant settings. In this phase I study,
      neratinib was combined with trastuzumab and paclitaxel in metastatic HER2
      positive patients. METHODS: Twenty-one patients entered this dose-escalation
      study to determine the maximum-tolerated dose, safety, and efficacy of neratinib
      (120 up to 240 mg/day) with trastuzumab (4 mg/kg IV loading dose, then 2 mg/kg IV
      weekly), and paclitaxel (80 mg/m(2) IV days 1, 8, and 15 of a 28-day cycle) in
      women with HER2-positive metastatic breast cancer previously treated with anti
      HER agent(s) and a taxane. RESULTS: The recommended phase II dose of neratinib
      with trastuzumab and paclitaxel was 200 mg/day. Common grade 3/4 adverse events
      were diarrhea (38 %), dehydration (14 %), electrolyte imbalance (19 %), and
      fatigue (19 %). With mandated primary diarrheal prophylaxis, >=grade 3 diarrhea
      was not observed. Objective responses, complete (CR) and partial (PR), occurred
      in eight patients (38 %), with a clinical benefit of CR + PR+ stable disease (SD)
      >=24 weeks in 11 patients (52 %). Median time-to-disease progression was 3.7
      months. CONCLUSIONS: Dual anti-HER blockade with neratinib and trastuzumab
      resulted in significant clinical benefit despite prior exposure to trastuzumab,
      lapatinib, T-DM1, a taxane, and multiple lines of chemotherapy. In selected
      populations, inhibiting multiple ErbB-family receptors may be more advantageous
      than single-agent inhibition. Based on favorable tolerance and efficacy, this
      three-drug combination will be further assessed in a randomized phase II
      neoadjuvant trial (NSABP FB-7:NCT01008150).

PMID- 24077917
TI  - [Healing times and the need for hospitalization for leg ulcers of different
      etiologies].
AB  - BACKGROUND: Leg ulcers are a symptom of a heterogeneous group of diseases. Their
      treatment causes substantial costs due to the long healing times and extensive
      wound care measures. There is a paucity of information about healing times and
      the necessity of hospital treatment for leg ulcers of different etiologies.
      MATERIALS AND METHODS: In this retrospective study, healing times and the
      frequency of in-hospital treatment of 355 patients with leg ulcers attending a
      wound care clinic of a university hospital were examined. RESULTS: The proportion
      of healed ulcers was 32.0% after 3 months and 54.3% after 6 months with an
      average treatment duration of 6.1 months for all ulcers. This proportion of
      healed ulcers was higher for venous ulcers with 45.5% after 3 months and 63.0%
      after 6 months, whereas only 30.0% of mixed arterial-venous ulcers and 35.0% of
      hypertensive ischemic leg ulcers (HYTILU) were healed after 6 months. Of the
      latter group, 71% of patients were hospitalized at least once during the
      observation period as compared to 47% of patients with a venous ulcer. The
      duration of the hospital stay was longer for mixed ulcers and HYTILU with an
      average of 30 days vs. 23 days for venous ulcers. CONCLUSIONS: These data
      indicate that the healing times of ulcers of different etiologies differ
      substantially and that especially ulcers with arteriosclerosis as a causative
      factor have longer healing times. The fact that they require in-hospital
      treatment more frequently and for longer periods has significant socio-economic
      consequences.

PMID- 24077918
TI  - Low aseptic loosening and revision rate in Zweymuller-Plus total hip arthroplasty
      with ceramic-on-ceramic bearings.
AB  - A recent comparative study reported lower revision rate and higher survival in
      ceramic-on-ceramic (CoC) than in metal-on-metal (MoM) coupling in Zweymuller-Plus
      THA. We retrospectively studied 87 consecutive patients (94 hips), who primarily
      received Zweymuller-Plus THA (SL-Plus stem, ceramic 28-mm ball head, Bicon cup)
      with third-generation CoC bearing surfaces for osteoarthritis. Survival, revision
      and osteolysis rate were studied and compared to those observed in historical
      series from this institution with the same THA and MoM articulation. The mean +/-
      SD follow-up was 7.4 +/- 1.7 years (range 6-10 years). Four hips (4%) in four
      patients were revised 1-6 years following primary implantation: one (1%) for
      aseptic loosening of SL-Plus stem and Bicon 5 years after index surgery; one (1%)
      for malpositioning of the Bicon and recurrent dislocations 1 year following
      implantation; and two (2%) for septic loosening 1 and 6 years postoperatively.
      Intraoperatively on inspection, there were neither findings for impingement in
      the revised hips, nor fracture of the Bicon ceramic inlay and ball head.
      Expansile osteolysis was shown around SL-Plus stem and Bicon in the revised for
      aseptic loosening hip. With revision of any component for aseptic loosening as
      the endpoint, the survival was 99% (95% CI 91-100%), while for revision for any
      reason, it was 95% (95% CI 87-98%) at 10 years. Zweymuller-Plus THA with CoC
      bearings showed, at mid-term follow-up, high survival and low revision rate for
      aseptic loosening. These rates were better than the historical series of the same
      THA with MoM articulation performed by the same surgeon. LEVEL OF EVIDENCE: Level
      IV.

PMID- 24077919
TI  - Anthelmintic effects of Salix babylonica L. and Leucaena  leucocephala Lam.
      extracts in growing lambs.
AB  - Twenty Katahdin * Pelibuey crossbreed male lambs, 3 to 4 months of age and 24 +/-
      0.3 kg of body weight, were used to study the anthelmintic effects of
      administering extracts of Salix babylonica L. (SB) and Leucaena leucocephala Lam.
      (LL). Lambs had not been treated with anthelmintics previously and were randomly
      allocated into four groups of five lambs each in a completely randomized design.
      Treatments were as follows: control (lambs fed on total mixed ration without
      extracts), SB (as control plus S. babylonica L. extract at 30 ml/day), LL (as
      control plus L. leucocephala Lam. extract at 30 ml/day), and SBLL (as control
      plus 30 ml/day of S. babylonica L. and L. leucocephala Lam. extracts in a 1:1
      (v/v) mixture) for 63 days. Extracts were orally administered before the 8:00
      a.m. feeding to each lamb. Rectal fecal samples were collected from each lamb at
      day 22 (P1), day 43 (P2), and day 63 (P3) of the experiment. Adult worm and egg
      counts were determined in each fecal sample immediately after collection. Plant
      secondary metabolites of total phenolics, saponins, and the aqueous fraction were
      50 % lower in the SB versus LL extracts. Overall, the oral administration of
      extracts has improved the egg and worm count reductions in lamb feces by 54, 47,
      and 40 % for LL, SB, and SBLL, respectively, versus the control lambs. Reductions
      of worm egg counts in lamb feces were higher (P < 0.05) in P2 and P3 versus P1.
      Extracts of SB and LL or possibly isolated bioactive compounds could be a
      promising alternative to conventional anthelmintics to treat gastrointestinal
      parasites of small ruminants. Such treatments could be used in control strategies
      against gastrointestinal nematodes in organic and conventional production
      systems.

PMID- 24077920
TI  - Body development, carcass, and meat quality of confined  lambs fed increasing
      levels of whole rice meal.
AB  - The objective of this trial was to evaluate the effect of whole rice meal (WRM)
      inclusion in the concentrate upon body development, carcass traits, and meat
      quality of lambs. Twenty-four castrated lambs with an average initial body weight
      of 17.90 +/- 2.72 kg were randomly blocked according to two genetic groups
      (Corriedale and Texel by Corriedale crossbreds). Three isocaloric (11.3 MJ/kg of
      metabolizable energy) and isonitrogenous (17 % crude protein) diets were offered
      to the animals for 74 days. Diets consisted of 40 % forage and 60 % concentrate
      diet, on a dry matter basis, with 0, 15, or 30 % of WRM inclusion into the
      concentrate. Body growth (after slaughter), carcass, and meat traits were
      evaluated on each animal. Results obtained indicated that genotype did not affect
      body growth, carcass, and meat traits except for yellowness. No significant
      interaction between diet and genotype were detected. Inclusion of up to 30 % WRM
      did not significantly (P > 0.05) affect body growth, carcass, and meat traits,
      except for meat color. Meat luminosity progressively increased (36.32 + 0.055X)
      while redness (15.13 - 0.03X) decreased with the inclusion of WRM in the diet,
      but still remained within acceptable values. The study indicates that WRM may be
      included up to 30 % in the concentrate replacing corn without adverse effects
      upon body development, carcass traits, and meat quality of lambs.

PMID- 24077921
TI  - Influence of S. babylonica extract on feed intake, growth  performance and diet
      in vitro gas production profile  in young lambs.
AB  - An experiment was completed to determine the effect of Salix babylonica (SB)
      extract supplementation to the diet of growing lambs. Eighteen Katahdin *
      Pelibuey male lambs (14 +/- 2 kg live body weight) were divided randomly in
      individual cages into three groups and fed three diets varying in SB: a control
      group was fed on total mixed ration (TMR) without SB (SB0), an SB25 group was fed
      on TMR plus SB extract at 25 mL/lamb/day, and an SB50 group was fed on TMR plus
      SB extract at 50 mL/lamb/day on dry matter intake (DMI), average daily gain
      (ADG), feed efficiency, and in vitro gas production (GP) in lambs fed on TMR. In
      vitro GP of the TMR fed to lambs was recorded at 2, 4, 6, 8, 10, 12, 24, 48, and
      72 h of incubation with 0, 0.6, 1.2, and 1.8 mL extract per gram of DM. Addition
      of SB extract at low and high doses improved the DMI of lambs by 59.9 and 33.2 %,
      respectively. Relative to the control, low and high extract doses achieved
      greater lamb ADG during the experimental period. The asymptotic GP increased (P <
      0.05) with increasing dose of SB extract without affecting the rate of GP or the
      initial delay before GP begins. Linear increases for in vitro GP with advancing
      time with different SB extract doses were observed. It is suggested that the use
      of S. babylonica extract with the rate of 25 mL/lamb/day is beneficial to young
      lamb's performance growth and thus can be safely used as a feed additive in diets
      without any negative effects on animal health.

PMID- 24077922
TI  - Production and economic performance of F1-crossbred dairy  cattle fed non
      conventional protein supplements in Zimbabwe.
AB  - The effects of supplementing crossbred cows with non-conventional protein sources
      on dry matter intake, milk yield parameters and economic returns were
      investigated. Twenty-five lactating F1 Holstein-Mashona crossbreds averaging 115
      +/- 24 days in milk were used. Five treatments, total mixed ration (TMR), urea
      treated maize stover, untreated maize stover, Macroptilium atropurpureum
      (Siratro) hay and veld hay, were randomly assigned to cows and replicated five
      times in a completely randomised design. Nutrient composition, intake, milk yield
      and economic returns were determined. M. atropurpureum hay, urea-treated maize
      stover and TMR had equal crude protein content. Daily dry matter intake and yield
      differed significantly among the treatment diets (P < 0.05). Cows on TMR, urea
      treated maize stover and M. atropurpureum consumed more (P < 0.05) than cows on
      untreated maize stover and veld hay. Supplementing with TMR, urea-treated maize
      stover and M. atropurpureum hay increased (P < 0.05) milk yields. Mean daily milk
      yield was highest for cows supplemented with urea-treated maize stover. Percent
      fat, protein and total solids in milk from cows fed urea-treated stover compared
      favourably to that of milk for cows supplemented with TMR. Income over supplement
      cost was highest for cows supplemented with M. atropurpureum hay and urea-treated
      maize stover. Urea-treated maize stover and M. atropurpureum can therefore be
      used as a replacer protein supplements for dairy cattle in Zimbabwe.

PMID- 24077923
TI  - The up-regulation of histone deacetylase 8 promotes proliferation and inhibits
      apoptosis in hepatocellular carcinoma.
AB  - BACKGROUND: Histone deacetylase 8 (HDAC8), a member of class I HDACs, has been
      reported to be involved in transcriptional regulation, cell cycle progression,
      and developmental events, and several studies have shown that HDAC8 plays a
      critical role in tumorigenesis. However, the expression level and the potential
      role of HDAC8 in hepatocellular carcinoma (HCC) remain unclear. AIM: The purpose
      of this study was to investigate protein expression of HDAC8 in HCC tissues and
      the effects of HDAC8 knockdown on the proliferation and apoptosis of liver cancer
      cells, and to explore the possible mechanisms. METHODS: First, we used
      quantitative real-time reverse transcription polymerase chain reaction (qRT-PCR),
      immunohistochemical staining, and western blot to examine the mRNA and protein
      expression of HDAC8 in HCC cell lines and tissues. Then, we assessed the
      correlation between clinicopathological parameters and the protein expression of
      HDAC8. Furthermore, we employed the interfering RNA method to explore the
      potential role of HDAC8 in HCC progression in vitro. RESULTS: Our results showed
      that expression of HDAC8 was significantly up-regulated both in HCC cell lines
      and tumor tissues compared to human normal liver cell line LO2 and corresponding
      non-tumor tissues. Moreover, we found that HDAC8 knockdown could dramatically
      inhibit HCC cell proliferation and enhance the apoptosis rate in vitro. Western
      blot revealed that intrinsic apoptotic pathway proteins, including BAX, BAD, and
      BAK, were elevated after HDAC8 knockdown. The cleavage of caspase-3 and PARP,
      which are downstream of intrinsic apoptotic pathway, were also enhanced. In
      addition, suppression of HDAC8 also elevated the expression of p53 and
      acetylation of p53 at Lys382, whereas the acetylation of p53 at Lys373 did not
      change. CONCLUSIONS: Our study revealed that HDAC8 was overexpressed in HCC.
      HDAC8 knockdown suppresses tumor growth and enhances apoptosis in HCC via
      elevating the expression of p53 and acetylation of p53 at Lys382. HDAC8 might
      serve as a potential therapeutic target in HCC.

PMID- 24077924
TI  - Donor factors similarly impact survival outcome after liver transplantation in
      hepatocellular carcinoma and non-hepatocellular carcinoma patients.
AB  - BACKGROUND: Many have advocated the preferential use of high risk allografts for
      hepatocellular carcinoma patients undergoing liver transplantation.
      Hepatocellular carcinoma (HCC) patients tend to have relatively preserved liver
      function, and their outcome is felt to be driven largely by tumor-related
      factors. AIM: The aim of this study was to compare the relative importance of
      donor versus recipient factors on post-orthotopic liver transplantation survival
      among HCC and non-HCC recipients. METHODS: The study group included Scientific
      Registry of Transplant Recipients data on adult recipients of deceased donor
      liver transplants from February 2002 through December 2008. Recipients were
      classified as HCC based on MELD exception applications and were compared to all
      other recipients. Predictors of post-LT survival were identified by Cox
      regression. To test whether donor factors have less impact on survival in HCC
      patients, interaction terms were created between HCC diagnosis and donor factors.
      RESULTS: Of the 40,212 DDLTs during the study period, 29,020 (72 %) met study
      criteria. A total of 7,786 (27 %)were transplanted with a diagnosis of HCC. The
      mean donor risk index was 1.5 in both cohorts. The 1-/5-year survival was 88 %/68
      % and 87 %/74 % among HCC and non-HCC recipients, respectively (p?0.0001). On
      multivariate analysis, there was no statistically significant interaction between
      HCC diagnosis and DRI (HR 0.94,p = 0.317). Likewise, no interaction was seen
      between HCC diagnosis and individual donor factors. In both groups, donor and
      recipient factors carried similar weight in determining post-LT survival.
      CONCLUSIONS: Contrary to previous assumptions, donor factors play a similar role
      in determining survival post-LT among HCC patients and non-HCC patients.

PMID- 24077925
TI  - Spatial scaling relationships for spread of disease caused by a wind-dispersed
      plant pathogen.
AB  - Spatial scale is of great importance to understanding the spread of organisms
      exhibiting long-distance dispersal (LDD). We tested whether epidemics spread in
      direct proportion to the size of the host population and size of the initial
      disease focus. This was done through analysis of a previous study of the effects
      of landscape heterogeneity variables on the spread of accelerating epidemics of
      wheat (Triticum aestivum) stripe rust, caused by the fungus Puccinia striiformis
      f. sp. tritici. End-of-season disease gradients were constructed by estimating
      disease prevalence at regular distances from artificially inoculated foci of
      different sizes, in field plots of different dimensions. In one set of
      comparisons, all linear dimensions (plot width and length, focus width and
      length, and distance between observation points) differed by a factor of four.
      Disease spread was substantially greater in large plot/large focus treatments
      than in small plot/small focus treatments. However, when disease gradients were
      plotted using focus width as the unit distance, they were found to be highly
      similar, suggesting a proportional relationship between focus or plot size and
      disease spread. A similar relationship held when comparing same-size plots
      inoculated with different-sized foci, an indication that focus size is the driver
      of this proportionality. Our results suggest that power law dispersal of LDD
      organisms results in scale-invariant relationships, which are useful for better
      understanding spatial spread of biological invasions, extrapolating results from
      small-scale experiments to invasions spreading over larger scales, and predicting
      speed and pattern of spread as an invasion expands.

PMID- 24077926
TI  - Religiosity/spirituality of German doctors in private practice and likelihood of
      addressing R/S issues with patients.
AB  - This study examined the self-assessed religiosity and spirituality (R/S) of a
      representative sample of German physicians in private practice (n = 414) and how
      this related to their addressing R/S issues with patients. The majority of
      physicians (49.3 %)reported a Protestant denomination, with the remainder
      indicating mainly either Catholic(12.5 %) or none (31.9 %). A significant
      proportion perceived themselves as either religious(42.8 %) or spiritual (29.0
      %). Women were more likely to rate themselves R/S than did men. Women (compared
      to men) were also somewhat more likely to attend religious services (7.4 vs. 2.1
      % at least once a week) and participate in private religious activities(14.9 vs.
      13.7 % at least daily), although these differences were not statistically
      significant.The majority of physicians (67.2 %) never/seldom addressed R/S issues
      with a typical patient. Physicians with higher self-perceived R/S and more
      frequent public and private religious activity were much more likely to address
      R/S issues with patients. Implications for patient care and future research are
      discussed.

PMID- 24077927
TI  - Revisiting a hoary chestnut: the nature of early cattle domestication in North
      East Africa.
AB  - It has been almost three decades since the Wendorf & Schild-Andrew Smith debate
      over the timing and location of domesticated cattle in North Africa reached its
      climax. The time is now appropriate for a review of the old models in light of
      subsequent anatomical and genetic data which have come to light. This article
      summarises the main issues and models, and attempts to provide suggestions for
      future investigations.

PMID- 24077928
TI  - Optimizing content for pre-exposure prophylaxis (PrEP) counseling for men who
      have sex with men: Perspectives of PrEP users and high-risk PrEP naive men.
AB  - Existing trials of antiretroviral (ARV) medication as chemoprophylaxis against
      HIV reveal that the degree of protection is primarily dependent on product
      adherence. However, there is a lack of data on targets for behavioral
      interventions to improve adherence to ARV as prevention. Information from
      individuals who have used ARV as pre-exposure prophylaxis (PrEP) can inform
      behavioral intervention development. Thirty-nine HIV-uninfected MSM at high risk
      for HIV acquisition participated in one of four semi-structured focus groups. Two
      of the focus groups consisted of MSM who had been prescribed and used PrEP in the
      context of a clinical trial; the other two consisted of high-risk MSM who had not
      previously used PrEP. An in-depth, within-case/across-case content analysis
      resulted in six descriptive themes potentially salient for a PrEP adherence
      behavioral intervention: (1) motivations to use PrEP, (2) barriers to PrEP use,
      (3) facilitators to PrEP use, (4) sexual decision-making in the context of PrEP,
      (5) prospective PrEP education content, and, (6) perceived effective
      characteristics of PrEP delivery personnel. Addressing these themes in behavioral
      interventions in the context of prescribing PrEP may result in the optimal
      "packaging" public health programs that implement PrEP for high-risk MSM.

PMID- 24077929
TI  - Opioid analgesic misuse is associated with incomplete antiretroviral adherence in
      a cohort of HIV-infected indigent adults in San Francisco.
AB  - There is little or no data examining the association between either pain or the
      use or misuse of opioid analgesic with adherence to antiretroviral medications
      (ARVs) among HIV-infected adults. We interviewed a community-based cohort of HIV
      infected indigent adults prescribed antiretroviral medications (ARVs) quarterly
      to examine the association between (1) pain, (2) receipt of opioid analgesics,
      and (3) opioid analgesic misuse with self-reported ARV adherence. Of 281
      participants, most (82.5 %) reported severe or moderate pain, half (52.4 %)
      received a prescription for opioids, and one quarter (24.6 %) misused opioid
      analgesics. Most (71.9 %) reported >90 % ARV adherence. In a GEE model, neither
      pain (unadjusted OR 1.14, CI 0.90-1.45) nor prescription of opioid analgesics
      (unadjusted OR 1.11, CI 0.84-1.49) were significantly associated with ARV
      adherence. Misuse of opioid analgesics was associated with incomplete adherence
      (AOR 1.42, CI 1.09-1.86). Individuals who misuse opioid analgesics, like those
      who use illicit substances, may have difficulty adhering to medication regimens.

PMID- 24077930
TI  - Critical consciousness, racial and gender discrimination, and HIV disease markers
      in African American women with HIV.
AB  - Critical consciousness, the awareness of social oppression, is important to
      investigate as a buffer against HIV disease progression in HIV-infected African
      American women in the context of experiences with discrimination. Critical
      consciousness comprises several dimensions, including social group
      identification, discontent with distribution of social power, rejection of social
      system legitimacy, and a collective action orientation. The current study
      investigated self-reported critical consciousness as a moderator of perceived
      gender and racial discrimination on HIV viral load and CD4+ cell count in 67
      African American HIV-infected women. Higher critical consciousness was found to
      be related to higher likelihood of having CD4+ counts over 350 and lower
      likelihood of detectable viral load when perceived racial discrimination was
      high, as revealed by multiple logistic regressions that controlled for highly
      active antiretroviral therapy (HAART) adherence. Multiple linear regressions
      showed that at higher levels of perceived gender and racial discrimination, women
      endorsing high critical consciousness had a larger positive difference between
      nadir CD4+ (lowest pre-HAART) and current CD4+ count than women endorsing low
      critical consciousness. These findings suggest that raising awareness of social
      oppression to promote joining with others to enact social change may be an
      important intervention strategy to improve HIV outcomes in African American HIV
      infected women who report experiencing high levels of gender and racial
      discrimination.

PMID- 24077931
TI  - Outcomes of HIV-infected patients receiving care at multiple clinics.
AB  - Receiving care at multiple clinics may compromise the therapeutic patient
      provider alliance and adversely affect the treatment of people living with HIV.
      We evaluated 12,759 HIV-infected adults in Philadelphia, PA between 2008 and 2010
      to determine the effects of using multiple clinics for primary HIV care. Using
      generalized estimating equations with logistic regression, we examined the
      relationship between receiving care at multiple clinics (>= 1 visit to two or
      more clinics during a calendar year) and two outcomes: (1) use of ART and (2) HIV
      viral load <= 200 copies/mL for patients on ART. Overall, 986 patients (8 %)
      received care at multiple clinics. The likelihood of attending multiple clinics
      was greater for younger patients, women, blacks, persons with public insurance,
      and for individuals in their first year of care. Adjusting for sociodemographic
      factors, patients receiving care at multiple clinics were less likely to use ART
      (AOR = 0.62, 95 % CI 0.55-0.71) and achieve HIV viral suppression (AOR = 0.78, 95
      % CI 0.66-0.94) than individuals using one clinic. Qualitative data are needed to
      understand the reasons for visiting multiple clinics.

PMID- 24077932
TI  - Fast state-space methods for inferring dendritic synaptic connectivity.
AB  - We present fast methods for filtering voltage measurements and performing optimal
      inference of the location and strength of synaptic connections in large dendritic
      trees. Given noisy, subsampled voltage observations we develop fast l1-penalized
      regression methods for Kalman state-space models of the neuron voltage dynamics.
      The value of the l1-penalty parameter is chosen using cross-validation or, for
      low signal-to-noise ratio, a Mallows' Cp-like criterion. Using low-rank
      approximations, we reduce the inference runtime from cubic to linear in the
      number of dendritic compartments. We also present an alternative, fully Bayesian
      approach to the inference problem using a spike-and-slab prior. We illustrate our
      results with simulations on toy and real neuronal geometries. We consider
      observation schemes that either scan the dendritic geometry uniformly or measure
      linear combinations of voltages across several locations with random
      coefficients. For the latter, we show how to choose the coefficients to offset
      the correlation between successive measurements imposed by the neuron dynamics.
      This results in a "compressed sensing" observation scheme, with an important
      reduction in the number of measurements required to infer the synaptic weights.

PMID- 24077933
TI  - Development of spatial coarse-to-fine processing in the visual pathway.
AB  - The sequential analysis of information in a coarse-to-fine manner is a
      fundamental mode of processing in the visual pathway. Spatial frequency (SF)
      tuning, arguably the most fundamental feature of spatial vision, provides
      particular intuition within the coarse-to-fine framework: low spatial frequencies
      convey global information about an image (e.g., general orientation), while high
      spatial frequencies carry more detailed information (e.g., edges). In this paper,
      we study the development of cortical spatial frequency tuning. As feedforward
      input from the lateral geniculate nucleus (LGN) has been shown to have
      significant influence on cortical coarse-to-fine processing, we present a firing
      rate based thalamocortical model which includes both feedforward and feedback
      components. We analyze the relationship between various model parameters
      (including cortical feedback strength) and responses. We confirm the importance
      of the antagonistic relationship between the center and surround responses in
      thalamic relay cell receptive fields (RFs), and further characterize how specific
      structural LGN RF parameters affect cortical coarse-to-fine processing. Our
      results also indicate that the effect of cortical feedback on spatial frequency
      tuning is age-dependent: in particular, cortical feedback more strongly affects
      coarse-to-fine processing in kittens than in adults. We use our results to
      propose an experimentally testable hypothesis for the function of the extensive
      feedback in the corticothalamic circuit.

PMID- 24077934
TI  - Cardiac morbidity of carotid endarterectomy using regional anesthesia is similar
      to carotid stent angioplasty.
AB  - Carotid artery stenting (CAS) was presented by carotid revascularization
      endarterectomy versus stenting trial as a minimally invasive approach with less
      risk of postoperative myocardial infarction (MI) when compared to carotid
      endarterectomy (CEA). Our study aimed to compare the postoperative MI rate for
      CAS with CEA under general anesthesia (GA) and local anesthesia (LA). A
      retrospective study was conducted at our institution comparing CAS with CEA under
      LA and CEA under GA. Thirty-day postoperative MI and strokes were evaluated for
      the different subgroups. A total of 1127 procedures were included in the
      analysis: 421 CEAs under GA, 611 CEAs under LA, and 95 CAS. No significant
      difference in postoperative MI was encountered between CAS and CEA under LA (0.2%
      vs 1.1%, P = .25). The CEA under GA was found to have a statistically significant
      higher risk of MI compared to LA (1.2% vs 0.2%, P = .044). Our evidence suggests
      that CEA under LA does not have an increased risk of MI compared to CAS. 

PMID- 24077935
TI  - The impact of CYP2D6 polymorphisms on the pharmacokinetics of codeine and its
      metabolites in Mongolian Chinese subjects.
AB  - PURPOSE: Codeine is an analgesic drug acting on MU-opioid receptors predominantly
      via its metabolite morphine formed almost exclusively by CYP2D6. Genetic
      polymorphisms in CYP2D6 are associated with diminished pain relief and/or severe
      opioid side effects. In Chinese individuals, CYP2D6*10 is the most common allele
      with reduced enzyme activity. In this study, we investigated the effect of this
      allele on the pharmacokinetics of codeine and its metabolites. METHOD: A blood
      sample was collected from healthy Mongolian volunteers for CYP2D6 genotyping
      using a PCR-RFLP assay. A pharmacokinetic study was then carried out in three
      groups with CYP2D6*1/*1 (n=10), CYP2D6*1/*10 (n=10) and CYP2D6*10/*10 (n=9)
      genotypes by collecting serial blood samples for determination of plasma levels
      of codeine and its metabolites, morphine, morphine 3-glucuronide (M3G) and
      morphine 6-glucuronide (M6G) before and after a single 30-mg oral dose of codeine
      phosphate. Codeine and its metabolites were measured by LC-MS/MS. RESULTS: No
      significant differences were observed in the pharmacokinetic parameters of
      codeine in the three genotype groups. However, the C( max) and AUC(0-infinity) of
      morphine, M3G and M6G were significantly different between the study groups
      (P<0.05). Compared with the *1/*1 group, the AUC(0-infinity) for morphine in the
      *1/*10 and *10/*10 groups decreased by ratios (95 % CI) of 0.93 (0.26-1.59) and
      0.494 (0.135-0.853) respectively. Corresponding ratios for M3G were 0.791 (0.294
      1.288) and 0.615 (0.412-0.818) and for M6G were 0.643 (0.39-0.957) and 0.423
      (0.267-0.579). CONCLUSION: This study demonstrates that the CYP2D6*10 allele
      plays an important role in the pharmacokinetics of the O-demethylated metabolites
      of codeine after oral administration.

PMID- 24077936
TI  - Effects of exercise training on sleep apnea: a meta-analysis.
AB  - BACKGROUND: Several studies have shown a favorable effect of supervised exercise
      training on obstructive sleep apnea (OSA). This meta-analysis was conducted to
      analyze the data from these studies on the severity of OSA (primary outcome) in
      adults. Secondary outcomes of interest included body mass index (BMI), sleep
      efficiency, daytime sleepiness and cardiorespiratory fitness. METHODS: Two
      independent reviewers searched PubMed and Embase (from inception to March 6,
      2013) to identify studies on the effects of supervised exercise training in
      adults with OSA. Pre- and postexercise training data on our primary and secondary
      outcomes were extracted. RESULTS: A total of 5 studies with 6 cohorts that
      enrolled a total of 129 study participants met the inclusion criteria. The pooled
      estimate of mean pre- to postintervention (exercise) reduction in AHI was -6.27
      events/h (95 % confidence interval [CI] -8.54 to -3.99; p < 0.001). The pooled
      estimates of mean changes in BMI, sleep efficiency, Epworth sleepiness scale and
      VO2 peak were -1.37 (95 % CI -2.81 to 0.07; p = 0.06), 5.75 % (95 % CI 2.47-9.03;
      p = 0.001), -3.3 (95 % CI -5.57 to -1.02; p = 0.004), and 3.93 mL/kg/min (95 % CI
      2.44-5.42; p < 0.001), respectively. CONCLUSIONS: This meta-analysis shows a
      statistically significant effect of exercise in reducing the severity of sleep
      apnea in patients with OSA with minimal changes in body weight. Additionally, the
      significant effects of exercise on cardiorespiratory fitness, daytime sleepiness,
      and sleep efficiency indicate the potential value of exercise in the management
      of OSA.

PMID- 24077937
TI  - Involvement of galectin-1 in reproduction: past, present and future.
AB  - BACKGROUND: After recognition of its pivotal contribution to fetomaternal
      tolerance, the study of galectin-1 (gal-1) functions in the context of pregnancy
      became an attractive topic in reproductive medicine. Despite considerable
      advances in the understanding of the immuno- and growth-regulatory properties of
      gal-1 at the fetal-maternal interface, many functional aspects of this lectin in
      reproduction are only emerging. METHODS: The published literature was searched
      using Pubmed focusing on gal-1 signalling and functional properties at the
      maternal-fetal interface, including data on its implication in pregnancy
      disorders and malignancies of the female reproductive system. Papers discussing
      animal and human studies were included. RESULTS: This review provides an overview
      of gal-1 functions during pregnancy, such as modulation of maternal immune
      responses and roles in embryo implantation and placentation. We also emphasize
      the role of gal-1 in key regulatory processes, including trophoblast migration,
      invasion, syncytium formation and expression of non-classical MHC class I
      molecules (HLA-G). In addition, we argue in favour of gal-1 pro-angiogenic
      properties, as observed in tumourigenesis and other pathological settings, and
      its implication in the angiogenesis process associated with early gestation.
      CONCLUSION: The involvement of gal-1 in the regulation of different processes
      during the establishment, development and maintenance of pregnancy could be
      described as unique. Gal-1 has emerged as an important lectin with major
      functions in pregnancy.

PMID- 24077938
TI  - Childbearing attitudes and decisions of young breast cancer survivors: a
      systematic review.
AB  - BACKGROUND: Young breast cancer survivors often need to deal with adverse effects
      of treatments on fertility and complex reproductive decisions. In this systematic
      review, we highlight what is known about childbearing and parenthood attitudes
      and decisions of young breast cancer survivors from their own perspective.
      METHODS: We conducted manual and electronic searches on Pubmed, PsychInf and
      CINAHL databases for articles, published in English between 1 January 1990 and 31
      October 2012, that assessed childbearing, pregnancy and parenthood
      attitudes/decisions of female breast cancer survivors (premenopausal and/or <50
      years old). Eligible articles were classified into quantitative studies,
      qualitative studies and mixed methods studies. Data from each study were
      individually extracted by all the authors, and standardized tables were created
      and discussed to ensure congruence of the information extracted. RESULTS: Of the
      493 publications identified in PubMed (results are presented for PubMed searches
      as the other databases did not yield any new relevant papers), 8 met the
      inclusion criteria, in addition to 2 publications retrieved manually. A total of
      10 studies provided information on pregnancy and parenthood attitudes and
      decisions, in addition to risks and benefits of childbearing after breast cancer.
      Survivors had mixed attitudes towards the issue. Fear associated with future
      pregnancy was reported, namely the risk of cancer recurrence. However, for many
      survivors, pregnancy and parenthood can represent normalcy, happiness and life
      fulfilment. CONCLUSIONS: Childbearing after breast cancer is an important issue
      for survivors. Future larger and prospective studies should be implemented to
      increase certainty of conclusions of current research. Clinicians may benefit
      from a deeper understanding of the importance of pregnancy and parenthood to
      survivors in order to provide the needed educational and psychosocial support
      services, overcome misinformation and better assist women with their fertility
      related decisions.

PMID- 24077939
TI  - The relationship between intra-articular meniscal, chondral, and ACL lesions:
      finding from 1,774 knee arthroscopy patients and evaluation by gender.
AB  - Knowing the relationship between diagnoses is important in knee arthroscopy in
      terms of defining possible treatment modalities preoperatively. The purpose of
      our study was to define the diagnoses made intraoperatively through knee
      arthroscopy and the relationships between them. We evaluated the results of knee
      arthroscopies performed over a 10-year period. The sites and sizes of chondral
      lesions, the existence of anterior cruciate ligament (ACL) injury, and the sites
      of meniscal lesions were noted for a total of 1,774 patients. The relationships
      between these lesions were evaluated statistically. Chondral lesions and
      posterior medial meniscal tears were predominant in females, whereas complete ACL
      tears were predominant in males. ACL tears were commonly accompanied by medial
      and lateral meniscal bucket-handle tears. In cases with advanced chondral
      lesions, medial and lateral posterior meniscal and lateral anterior meniscal
      tears were more common. According to our results, posterior tears of the medial
      menisci, medial and lateral femoral condyles, lateral tibial plateau type 3 or 4
      cartilage lesions, and the rate of diagnostic arthroscopy were higher in females,
      while middle substance and bucket-handle tears of medial menisci and total
      rupture of the ACL were more common in males. ACL injuries were seen to coexist
      with medial or lateral menisci bucket-handle tears, with no relationship between
      the site or size of the chondral lesions. A relationship between medial and
      lateral meniscal tears and the site of femoral and tibial chondral surface
      lesions was detected. 

PMID- 24077940
TI  - Partial rupture of the hamstring muscle complex: a literature   review on
      treatment options.
AB  - Injuries of the hamstring muscle complex (HMC) often affect athletes
      participating in specific sporting activities. Mild injuries that constitute a
      mere strain of the muscle can be managed symptomatically, while severe injuries
      often require surgical intervention to precipitate a return to function.
      Neglected injuries usually result in a long-term functional impairment.
      Therefore, surgical reconstruction of the HMC is advised for both partial and
      complete lesions. Without acute repair, a chronic lesion referred to as hamstring
      syndrome can result due to dysfunction of the HMC. Surgical intervention is
      usually recommended. A case of a chronic severe partial injury to the HMC managed
      conservatively in a 49-year old female is presented to illustrate the level of
      function that can be achieved after non-operative management. The clinical and
      radiological findings are presented 18 months post-injury along with a review of
      the current literature. There are no previous reports in the literature
      describing this scenario. This case indicates the need for re-evaluation in
      treatment options in partial hamstring muscle ruptures. A surgical treatment of
      partial rupture should be considered more often as an adequate treatment option
      and cofactors that influence the prognosis must be revealed. The indication of
      surgical intervention should be re-evaluated within the first months in case of
      conservative treatment.

PMID- 24077942
TI  - Palliative stent for malignant colonic obstruction by extracolonic malignancy: a
      comparison with colorectal cancer.
AB  - BACKGROUND AND AIM: Palliative self-expandable metal stent placement for colonic
      obstruction arising from an extracolonic malignancy might be as useful as that
      for colorectal cancer, but data are limited. The purposes of this study were to
      investigate success and complications of stent placement in patients with
      extracolonic malignancy and to compare long-term clinical outcomes for an
      extracolonic malignancy group with those for a colorectal cancer group. PATIENTS
      AND METHODS: We reviewed short-term and long-term outcomes for patients treated
      with palliative stents for colonic obstruction by extracolonic malignancy (n =
      44) or unresectable colorectal cancer (n = 53) from January 2006 to March 2011.
      RESULTS: Neither the technical success (93.2 vs. 98.1 %, respectively; P = 0.326)
      nor clinical success (77.3 vs. 84.9 %, respectively; P = 0.433) of stent
      placement differed significantly in the two groups. Complications as a result of
      stent placement also differed only slightly in the two groups (perforation: 4.8 %
      (two cases) vs. 0 %, respectively; migration: 4.8 vs. 5.8 %, respectively, P =
      0.343). With regard to long-term outcomes, although stent patency was shorter in
      the extracolonic malignancy group (P = 0.015), because overall survival in this
      group was also shorter (P = 0.018), it was sufficient for palliative purposes.
      CONCLUSIONS: Palliative stent placement was equally effective and safe for
      treatment of colonic obstruction arising from either extracolonic malignancy or
      unresectable colorectal cancer. Even in cases of colonic obstruction arising from
      extracolonic malignancy, stent placement should be considered as primary
      palliative therapy.

PMID- 24077943
TI  - Severe iron deficiency: rare etiology, easy treatment.

PMID- 24077944
TI  - Characterization of a novel tumorigenic esophageal adenocarcinoma cell line:
      OANC1.
AB  - BACKGROUND: Esophageal adenocarcinoma (EAC) has a very high case fatality rate
      and is one of the fastest rising cancers worldwide. At the same time, research
      into EAC has been hampered by a relative lack of pre-clinical models, including
      representative cell lines. AIM: The purpose of this study was to establish and
      characterize a new EAC cell line. METHODS: Tumor cells were isolated from EAC
      tissue by enzymatic digestion. Origin of the cell line was confirmed by
      microsatellite based genotyping. A panel of cancer-related genes was screened for
      mutations by targeted deep sequencing, Sanger sequencing and high resolution
      melting.CDKN2A promoter methylation was assessed by methylation specific high
      resolution melting. HER2 amplification was assessed by fluorescent in situ
      hybridization. Immunohistochemistry was used to assess expression of markers in
      xenografts grown in SCID mice. RESULTS: A novel EAC cell line, OANC1, was derived
      from a Barrett's-associated EAC. Microsatellite-based genotyping of OANC1 and
      patient DNA confirmed the origin of the cell line. Sequencing of OANC1 DNA
      identified homozygous TP53 missense (c.856G[A, p.E286K)and SMAD4 nonsense
      (c.1333C[T, p.R445X) mutations.OANC1 are tumorigenic when injected sub
      cutaneously into SCID mice and xenografts were positive for columnar, glandular
      and intestinal epithelial markers commonly expressed in EAC. Xenografts exhibited
      strong p53 expression, consistent with a TP53 mutation. Some proteins, including
      p16, EGFR and b-catenin, had heterogeneous expression patterns across xenograft
      cross-sections, indicative of tumor heterogeneity. CONCLUSIONS: OANC1 represents
      a valuable addition to the limited range of pre-clinical models for EAC. This new
      cell line will be a useful model system for researchers studying both basic and
      translational aspects of this disease.

PMID- 24077945
TI  - RGS3 controls T lymphocyte migration in a model of Th2-mediated airway
      inflammation.
AB  - T cell migration toward sites of antigen exposure is mediated by G protein
      signaling and is a key function in the development of immune responses.
      Regulators of G protein signaling (RGS) proteins modulate G protein signaling;
      however, their role in the regulation of adaptive immune responses has not been
      thoroughly explored. Herein we demonstrated abundant expression of the Gi/Gq
      specific RGS3 in activated T cells, and that diminished RGS3 expression in a T
      cell thymoma increased cytokine-induced migration. To examine the role of
      endogenous RGS3 in vivo, mice deficient in the RGS domain (RGS3(DeltaRGS)) were
      generated and tested in an experimental model of asthma. Compared with littermate
      controls, the inflammation in the RGS3(DeltaRGS) mice was characterized by
      increased T cell numbers and the striking development of perivascular lymphoid
      structures. Surprisingly, while innate inflammatory cells were also increased in
      the lungs of RGS3(DeltaRGS) mice, eosinophil numbers and Th2 cytokine production
      were equivalent to control mice. In contrast, T cell numbers in the draining
      lymph nodes (dLN) were reduced in the RGS3(DeltaRGS), demonstrating a
      redistribution of T cells from the dLN to the lungs via increased RGS3(DeltaRGS)
      T cell migration. Together these novel findings show a nonredundant role for
      endogenous RGS3 in controlling T cell migration in vitro and in an in vivo model
      of inflammation.

PMID- 24077946
TI  - Efficient gene delivery to primary alveolar epithelial cells by nucleofection.
AB  - Primary alveolar epithelial cells play a pivotal role in lung research,
      particularly when focusing on gas exchange, barrier function, and transepithelial
      transport processes. However, efficient transfection of primary alveolar
      epithelial cells continues to be a major challenge. In the present study, we
      applied nucleofection, a novel method of gene and oligonucleotide delivery to the
      nucleus of cells by electroporation, to achieve highly efficient transfection of
      primary alveolar epithelial type II (ATII) cells. To quantify the amount of ATII
      cells effectively transfected, we applied a plasmid expressing GFP and assessed
      the amount of GFP-expressing cells by flow cytometry. Analysis of the
      nucleofected ATII cells revealed a concentration-dependent transfection
      efficiency of up to 50% when using 3-8 MUg plasmid DNA without affecting cell
      viability. Nucleofection of cultured A549 and H441 cells yielded similar
      transfection rates. Importantly, nucleofection of ATII cells did not interfere
      with the integrity of ATII monolayers even with use of relatively high
      concentrations of plasmid DNA. In subsequent studies, we also efficiently
      delivered small interfering RNAs to ATII cells by nucleofection, thereby
      silencing Akt and the multiligand receptor megalin, which has been recently shown
      to play a key role in removal of excess protein from the alveolar space, and
      effectively inhibited megalin-driven uptake and transcellular transport of
      albumin in ATII cells. Thus we report successful transfection of primary rat
      alveolar epithelial cells with both plasmids and oligonucleotides via
      nucleofection with high viability and consistently good transfection rates
      without impairing key physiological properties of the cells. 

PMID- 24077947
TI  - Decreased Kv1.5 expression in intrauterine growth retardation rats with
      exaggerated pulmonary hypertension.
AB  - Chronic hypoxia pulmonary hypertension (CH-PHT) in adulthood is likely to be of
      fetal origin following intrauterine growth retardation (IUGR). Oxygen (O2)
      sensitive voltage-gated potassium channels (Kv channels) in resistance pulmonary
      artery smooth muscle cells (PASMCs) play an important role in scaling pulmonary
      artery (PA) pressure. Expression and functional changes of Kv channels are
      determined, in part, by embryonic development. We hypothesized that O2-sensitive
      Kv channels play an important role in exaggerated CH-PHT following IUGR. We
      established a rat model of IUGR by restricting maternal food during the entire
      pregnancy and exposed IUGR rats and their age-matched controls aged 12 wk to
      hypoxia for 2 wk. We found that hypoxia exposure significantly induced increased
      PA pressure and thicker smooth muscle layer in the IUGR group relative to
      controls. We compared the constriction of the resistance PA to inhibitors of K+
      channels, 4-aminopyridine (4-AP), tetraethylammonium, and BaCl2. Despite the
      thickness of the smooth muscle layer, the constriction to 4-AP was significantly
      reduced in the IUGR group exposed to hypoxia. Consistent with these changes in
      pulmonary vascular reactivity, 2 wk of hypoxia induced weaker 4-AP-sensitive Kv
      currents in a single IUGR PASMC. Moreover, after 2 wk of hypoxia, Kv1.5
      expression in resistance PAs decreased significantly in the IUGR group.
      Overexpression of Kv1.5 in cultured PASMCs could offset hypoxia-induced cell
      proliferation and hypoxia-inhibited Kv currents in the IUGR group. These results
      suggest that the inhibited expression of Kv1.5 in PASMCs contribute to the
      development of exaggerated CH-PHT in IUGR rats during adulthood.

PMID- 24077948
TI  - Actin cytoskeleton redox proteome oxidation by cadmium.
AB  - Epidemiological studies associate environmental cadmium (Cd) exposure with the
      risk of lung diseases. Although mechanisms are not fully elucidated, several
      studies demonstrate Cd effects on actin and actin-associated proteins. In a
      recent study of Cd at concentrations similar to environmental exposures, we found
      that redox-dependent inflammatory signaling by NF-kappaB was sensitive to the
      actin-disrupting agent, cytochalasin D. The goal of the present study was to use
      mass spectrometry-based redox proteomics to investigate Cd effects on the actin
      cytoskeleton proteome and related functional pathways in lung cells at low
      environmental concentrations. The results showed that Cd under conditions that
      did not alter total protein thiols or glutathione redox state caused significant
      oxidation of peptidyl Cys of proteins regulating actin cytoskeleton.
      Immunofluorescence microscopy of lung fibroblasts and pulmonary artery
      endothelial cells showed that low-dose Cd exposure stimulated filamentous actin
      formation and nuclear localization of destrin, an actin-depolymerizing factor.
      Taken together, the results show that redox states of peptidyl Cys in proteins
      associated with actin cytoskeleton pathways are selectively oxidized in lung by
      Cd at levels thought to occur from environmental exposure. 

PMID- 24077949
TI  - Reduction of eotaxin production and eosinophil recruitment by pulmonary
      autologous macrophage transfer in a cockroach allergen-induced asthma model.
AB  - We sought to investigate the effects of cockroach allergen (CRA) exposure on the
      lung macrophage population to determine how different macrophage phenotypes
      influence exacerbation of disease. CRA exposure caused significantly reduced
      expression of CD86 on lung macrophages. These effects were not systemic, as
      peritoneal macrophage CD86 expression was not altered. To investigate whether
      naive macrophages could reduce asthma-like pulmonary inflammation, autologous
      peritoneal macrophages were instilled into the airways 24 h before the final CRA
      challenge. Pulmonary inflammation was assessed by measurement of airway
      hyperresponsiveness, mucin production, inflammatory cell recruitment, and
      cytokine production. Cell transfer did not have significant effects in control
      mice, nor did it affect pulmonary mucin production or airway hyperresponsiveness
      in control or CRA-exposed mice. However, there was significant reduction in the
      number of eosinophils recovered in the bronchoalveolar lavage (BAL) (5.8 * 105
      vs. 0.88 * 105), and total cell recruitment to the airways of CRA-exposed mice
      was markedly reduced (1.1 * 106 vs. 0.57 * 106). The reduced eosinophil
      recruitment was reflected by substantially lower levels of eosinophil peroxidase
      in the lung and significantly lower concentrations of eotaxins in BAL (eotaxin 1:
      3 pg/ml vs. undetectable; eotaxin 2: 2,383 vs. 131 pg/ml) and lung homogenate
      (eotaxin 1: 1,043 vs. 218 pg/ml; eotaxin 2: 10 vs. 1.5 ng/ml). We conclude that
      CRA decreases lung macrophage CD86 expression. Furthermore, supplementation of
      the lung cell population with peritoneal macrophages inhibits eosinophil
      recruitment, achieved through reduction of eotaxin production. These data
      demonstrate that transfer of naive macrophages will reduce some aspects of asthma
      like pulmonary inflammation in response to CRA.

PMID- 24077950
TI  - PECAM-1 and caveolae form the mechanosensing complex necessary for NOX2
      activation and angiogenic signaling with stopped flow in pulmonary endothelium.
AB  - We showed that stop of flow triggers a mechanosignaling cascade that leads to the
      generation of reactive oxygen species (ROS); however, a mechanosensor coupled to
      the cytoskeleton that could potentially transduce flow stimulus has not been
      identified. We showed a role for KATP channel, caveolae (caveolin-1), and NADPH
      oxidase 2 (NOX2) in ROS production with stop of flow. Based on reports of a
      mechanosensory complex that includes platelet endothelial cell adhesion molecule
      1 (PECAM-1) and initiates signaling with mechanical force, we hypothesized that
      PECAM-1 could serve as a mechanosensor in sensing disruption of flow. Using lungs
      in situ, we observed that ROS production with stop of flow was significantly
      reduced in PECAM-1(-/-) lungs compared with lungs from wild-type (WT) mice. Lack
      of PECAM-1 did not affect NOX2 activation machinery or the caveolin-1 expression
      or caveolae number in the pulmonary endothelium. Stop of flow in vitro triggered
      an increase in angiogenic potential of WT pulmonary microvascular endothelial
      cells (PMVEC) but not of PECAM-1(-/-) PMVEC. Obstruction of flow in lungs in vivo
      showed that the neutrophil infiltration as observed in WT mice was significantly
      lowered in PECAM-1(-/-) mice. With stop of flow, WT lungs showed higher
      expression of the angiogenic marker VEGF compared with untreated (sham) and PECAM
      1(-/-) lungs. Thus PECAM-1 (and caveolae) are parts of the mechanosensing
      machinery that generates superoxide with loss of shear; the resultant ROS
      potentially drives neutrophil influx and acts as an angiogenic signal. 

PMID- 24077951
TI  - Two-year clinical and radiologic follow-up of early RA patients treated with
      initial step up monotherapy or initial step down therapy with glucocorticoids,
      followed by a tight control approach: lessons from a cohort study in daily
      practice.
AB  - The objective of the study was to evaluate the effect of initial disease
      modifying antirheumatic drug (DMARD) combination therapy with steroids (ICTS) and
      DMARD monotherapy (IMT) on the clinical and radiologic evolution of patients with
      early rheumatoid arthritis (RA) over a 2-year treatment period, applying tight
      control (TC) in daily practice. Seventy-four DMARD-naive early RA patients
      received ICTS or IMT in a TC setting. Baseline and year 1 and year 2 X-rays of
      hands and feet were scored according to Sharp/van der Heijde. Rapid radiographic
      progression (RRP) was defined as total Sharp score (TSS) of >5 units/year. At
      year 1, both treatment groups achieved 50 % remission. At year 2, 37 % of IMT and
      60 % of ICTS patients were in remission, despite ICTS patients having initially a
      more severe RA profile. RRP was found in 4/74 patients at year 1: 3 IMT and 1
      ICTS patients. Remarkably, three of these four patients had no radiographic
      progression in the second year. Five other patients had RRP in the second year:
      four IMT and one ICTS patients. In a TC setting, ICTS and IMT can prevent
      radiographic progression in the majority of patients in the daily practice of a
      Belgian academic hospital over 2 years. ICTS seems to be more effective than IMT
      in achieving higher remission rates and less radiographic progression.

PMID- 24077952
TI  - Anti-apolipoprotein A-1 antibodies and carotid intima-media thickness in Egyptian
      women with systemic lupus erythematosus.
AB  - The objective of the study was to evaluate anti-apolipoprotein A-I (Apo A-I) and
      carotid intima-media thickness (cIMT) as cardiovascular risk factors in Egyptian
      women with systemic lupus erythematosus (SLE). The study included 160 subjects,
      80 women with SLE and 80 healthy women as a control group. Disease activity score
      (SLEDAI), disease damage index (SLICC/ACR), lipid profile, complement C3 and C4,
      high-sensitivity CRP (hsCRP), anti-dsDNA and anticardiolipin antibodies were
      evaluated in addition to anti-Apo A-I antibodies and cIMT. The mean age of
      patients was 28.35 +/- 7.06 years with mean disease duration of 4.58 +/- 3.36
      years. Anti-Apo A-I antibody titer was significantly higher in SLE patients than
      in controls (mean 35.3 +/- 6.8 vs. 21.4 +/- 5.91 U/L; P = 0.000). Carotid
      ultrasound showed significantly thickened intima in SLE patients compared with
      control subjects (mean thickness, 0.5 +/- 0.08 vs. 0.45 +/- 0.06 mm; P = 0.003).
      Correlation studies with other cardiovascular risk factors demonstrated
      significant associations between anti-Apo A-I and SLEDAI, SLICC/ACR, C3 and C4.
      On the other hand, cIMT showed significant association with age, systolic blood
      pressure, hsCRP and body mass index. Thus, SLE disease activity is associated
      with a significant increase in anti-Apo A-I titer. Also, increased cIMT might be
      a cardiovascular risk factor in Egyptian patients with SLE.

PMID- 24077954
TI  - Bactericidal genes of Staphylococcal bacteriophage Sb-1.
AB  - Bacteriophage genes offer a potential resource for development of new
      antibiotics. Here, we identify at least six genes of Staphylococcus aureus phage
      Sb-1 that have bactericidal activity when expressed in Escherichia coli. Since
      the natural host is gram-positive, and E. coli is gram-negative, it is likely
      that a variety of quite different bacterial pathogens would be susceptible to
      each of these bactericidal activities, which therefore might serve as the basis
      for development of new wide-spectrum antibiotics. We show that two of these gene
      products target E. coli protein synthesis.

PMID- 24077953
TI  - Insights on the genotype distribution among Cryptococcus neoformans and C. gattii
      Portuguese clinical isolates.
AB  - This study provides a comprehensive picture of the C. neoformans/C. gattii
      molecular types most often associated with human cryptococcosis in Portugal and
      assesses the impact of C. gattii in these infections. One hundred and twenty-two
      clinical isolates, from distinct patients, were identified as C. neoformans and
      genotyped by URA5-RFLP, with the molecular types VNI (45.5 %) and VNIII (30.9 %)
      being the most commonly found ones. The molecular types VNII (11.4 %) and VNIV
      (11.4 %) were less abundant. One patient was found to be infected with a VGII
      isolate. This patient exhibited unusual clinical symptoms of cryptococcosis,
      reinforcing the suspicion for the presence of a different genotypic pattern, as
      determined afterwards. This case was detected in 2007 and is the first report of
      a potential autochthonous C. gattii infection case in Portugal, as the patient
      revealed no historical record of travelling outside the country.

PMID- 24077955
TI  - Decreased expression of cystic fibrosis transmembrane conductance regulator
      impairs sperm quality in aged men.
AB  - Sperm quality declines with aging; however, the underlying molecular mechanism
      remains elusive. The cystic fibrosis transmembrane conductance regulator (CFTR)
      has been shown to play an essential role in fertilizing capacity of sperm and
      male fertility. This study aimed to investigate the involvement of age-dependent
      CFTR downregulation in lowering sperm quality in old age. Two hundred and one
      healthy fertile men of three age groups (20-40 years, n=64; 40-60 years, n=61;
      and >60 years, n=76) were recruited. Expression of CFTR was determined by RT-PCR,
      western blot, and immunofluorescence staining. Collected sperm were treated with
      CFTR inhibitor or potentiator. Sperm quality was assessed by motility and
      bicarbonate-induced capacitation. The results showed that the expression of CFTR
      on the equatorial segment and neck region of sperm was significantly decreased in
      an age-dependent manner. Reduction of CFTR expression in sperm from old men was
      correlated with lowered forward motility and decreased HCO3(-) sensitivity
      required for sperm capacitation. Activation of CFTR by genistein partially
      rescued the decreased forward motility in sperm from old men. Decreased CFTR
      expression in sperm was also found to be associated with lowered sperm quality in
      aging mice. These results suggest that age-dependent downregulation of CFTR in
      sperm leads to lowered sperm quality in old age sperm. CFTR may be a pontential
      target for rescuing sperm motility as well as a fertility indicator in old age
      men. 

PMID- 24077956
TI  - Ovarian signalling pathways regulated by leptin during the ovulatory process.
AB  - Leptin, a protein secreted by different tissues, is able to exert both
      stimulatory and inhibitory effects on the ovulatory process. Thus, we
      investigated whether these opposite effects involve changes in the ovarian
      signalling pathways in response to different levels of leptin. To this end, we
      performed both in vivo and in vitro assays using immature rats primed with
      gonadotrophins to induce ovulation. The acute treatment with leptin, which
      inhibits the ovulatory process, caused a significant decrease in the
      phosphorylation of both STAT3 and ERK1/2 and a simultaneous increase in
      suppressors of cytokine signalling 3 (SOCS3) protein. However, daily
      administration of a low dose of leptin, which induces the ovulatory process,
      showed increased phosphorylation of both STAT3 and ERK1/2 and a decreased
      expression of SOCS3 protein. Using ovarian explant cultures, we also found that
      leptin was able to activate both STAT3 and ERK1/2 at 10 ng/ml but only STAT3 at
      300-500 ng/ml. In addition, at 100-300 ng/ml, leptin increased protein but not
      mRNA expression of SOCS3. The addition of specific inhibitors of JAK/STAT and
      MAPK signalling pathways suppressed both the increase and the decrease in leptin
      induced progesterone secretion. These results indicate that i) different levels
      of leptin are able to regulate STAT3, ERK1/2 and SOCS3 at both intra- and extra
      ovarian level and that ii) the dual action of leptin on steroidogenesis seems to
      occur, at least in part, through both the ERK and STAT cascades.

PMID- 24077958
TI  - Effects of supplementing Leucaena leucocephala  and conserved forages from
      natural pasture  on the performance of grazing calves.
AB  - Twelve white Fulani * N'dama cross-bred calves weighing 83.79 +/- 1.16 kg were
      used in an 84-day experiment to investigate the utilization of forage resources
      from natural grazing land. The experimental diets were sole grazing, grazing +
      hay, grazing + silage and grazing + Leucaena leucocephala leaves. The calves were
      divided into four groups of three animals each and were randomly assigned to the
      four experimental diets. Crude protein (CP) contents of the forages ranged from
      59 to 171 g/kg dry matter (DM). Neutral detergent fibre (NDF) and acid detergent
      fibre (ADF) contents of the forages ranged from 560 to 705 g/kg DM and 363 to 440
      g/kg DM, respectively. Significantly (P < 0.05) higher values in mineral contents
      (Ca, K, P and Mg) were recorded for L. leucocephala leaves compared to other
      forage resources. Variations (P < 0.05) were observed in the average daily gain.
      Animals on grazing + L. leucocephala leaves diet had the highest (113 g/day)
      average daily gain, while those on sole grazing showed the least value (26.2
      g/day). Packed cell volume (PCV), total serum protein, urea and calcium
      concentration showed significant differences (P < 0.05). Effective utilization of
      forage resources from the natural pasture by the calves was attained on
      supplementation with conserved forages and L. leucocephala leaves without any
      deleterious effects on the haematological and serum parameters.

PMID- 24077957
TI  - A biologically constrained model of the whole basal ganglia addressing the
      paradoxes of connections and selection.
AB  - The basal ganglia nuclei form a complex network of nuclei often assumed to
      perform selection, yet their individual roles and how they influence each other
      is still largely unclear. In particular, the ties between the external and
      internal parts of the globus pallidus are paradoxical, as anatomical data suggest
      a potent inhibitory projection between them while electrophysiological recordings
      indicate that they have similar activities. Here we introduce a theoretical study
      that reconciles both views on the intra-pallidal projection, by providing a
      plausible characterization of the relationship between the external and internal
      globus pallidus. Specifically, we developed a mean-field model of the whole basal
      ganglia, whose parameterization is optimized to respect best a collection of
      numerous anatomical and electrophysiological data. We first obtained models
      respecting all our constraints, hence anatomical and electrophysiological data on
      the intrapallidal projection are globally consistent. This model furthermore
      predicts that both aforementioned views about the intra-pallidal projection may
      be reconciled when this projection is weakly inhibitory, thus making it possible
      to support similar neural activity in both nuclei and for the entire basal
      ganglia to select between actions. Second, we predicts that afferent projections
      are substantially unbalanced towards the external segment, as it receives the
      strongest excitation from STN and the weakest inhibition from the striatum.
      Finally, our study strongly suggests that the intrapallidal connection pattern is
      not focused but diffuse, as this latter pattern is more efficient for the overall
      selection performed in the basal ganglia.

PMID- 24077959
TI  - Microarrays as a diagnostic tool in prenatal screening strategies: ethical
      reflection.
AB  - Genomic microarray analysis is increasingly being applied as a prenatal
      diagnostic tool. Microarrays enable searching the genome at a higher resolution
      and with higher sensitivity than conventional karyotyping for identifying
      clinically significant chromosomal abnormalities. As yet, no clear guidelines
      exist on whether microarrays should be applied prenatally for all indications or
      only in selected cases such as ultrasound abnormalities, whether a targeted or
      genome-wide array should be used, and what these should include exactly. In this
      paper, we present some ethical considerations on the prenatal use of microarrays.
      There is a strong consensus, at least in Western countries, that the aim of
      prenatal screening for foetal abnormalities should be understood as facilitating
      autonomous reproductive choice for prospective parents. The tests offered should
      be valid and useful to reach that purpose. Against this background, we address
      several ethical issues raised by the prenatal application of microarrays. First,
      we argue that the general distinction between a targeted and a genome-wide
      microarray needs to be scrutinised. Then we examine whether microarrays are
      'suitable tests' to serve either a screening or a diagnostic purpose. Given the
      wide range of findings possibly generated by microarrays, the question arises
      whether microarrays actually promote or interfere with autonomous reproductive
      decision-making. Moreover, if variants of unknown clinical significance are
      identified, this adds to the burden and complexity of reproductive decision
      making. We suggest a qualified use of microarrays in the prenatal context.

PMID- 24077960
TI  - Do educational meetings and group detailing change adherence to drug formularies
      in hospitals? A cluster randomized controlled trial.
AB  - PURPOSE: The aim of this study was to examine whether educational meetings and
      group detailing could increase the use of drugs from the ward lists or the drug
      formulary in hospitals. METHODS: Twelve medical wards from two hospitals were
      randomized into three groups: control, basic and extended intervention. All wards
      had a ward list review before interventions. Moreover, the basic intervention
      consisted of an educational meeting, and the extended intervention included two
      group detailing sessions. The proportion of drugs used from the ward list or
      hospital drug formulary (HDF) was the primary outcome. Data (defined daily doses
      [DDDs], numbers and cost [Euros]) on drugs sold to the wards were retrieved from
      the two hospitals from 1 July 2011 to 31 August 2012. BASELINE DATA: from July to
      September 2011, and follow-up data: from June to August 2012. RESULTS: The
      proportion of formulary drugs used increased for the extended intervention group
      (0.04, range -0.02 to 0.09) and basic intervention group (0.03, range -0.03 to
      0.09) in comparison with a decrease in the control group (-0.01, range -0.03 to 
      0.02). The interventions did not significantly change odds for selecting drugs
      from the formulary in comparison with the control group (basic intervention: OR
      1.09 [95 % CI 0.81 to 1.46]; extended intervention: OR 1.00 [95 % CI 0.75 to
      1.35]). CONCLUSIONS: In this study, educational meetings and group detailing do
      not significantly improve adherence to ward lists or HDF. The adherence to the
      formularies at baseline was relatively high, which may explain why the
      interventions did not have a significant effect.

PMID- 24077961
TI  - Understanding how Latino parents choose beverages to serve to infants and
      toddlers.
AB  - To determine Latino parents' beliefs on the health effects of beverages on
      infants and toddlers, their sources of information on beverages and perceived
      barriers to following guidelines for healthy beverage consumption by children. We
      conducted 29 interviews with parents of Latino children ages 6-36 months. Parents
      were recruited in three community health centers in Northern California. The
      interviews were recorded, transcribed and analyzed using standard qualitative
      methods. The following dominant themes emerged. Parents believed that water and
      milk were healthy beverages for children and that sugar-sweetened beverages
      (SSBs) were unhealthy. Views on 100% fruit juice were mixed. Parents
      distinguished between homemade beverages such as "agua fresca" which they
      considered healthy, despite containing added sugar, and beverages from stores
      which were viewed as unhealthy. Participants' main source of information on
      beverages was the federal nutrition program for Women, Infants, and Children
      (WIC). Parents were confused, however, as to why WIC provides juice yet counseled
      parents to avoid giving their children juice. Parents preferred to receive
      information on beverages from experts. Differing practices among family members
      regarding which beverages they provide to children was the most important barrier
      to following beverage guidelines. Our study suggests that Latino parents are
      receptive to counseling on beverages from expert sources. Such counseling should
      address both store-bought and homemade beverages. The WIC program is a key source
      of information on beverages for Latino parents; thus counseling offered by WIC
      should be evidence-based and avoid mixed messages.

PMID- 24077962
TI  - Maternal depressive symptoms and weight-related parenting behaviors.
AB  - This study examined associations between mothers' depressive symptoms and
      parenting behaviors related to children's nutrition and physical activity. Data
      from the Early Childhood Longitudinal Study-Birth Cohort, a nationally
      representative study of children from infancy through kindergarten entry.
      Contemporaneous and lagged associations between maternal depressive symptoms and
      mothers' parenting behaviors were tested, controlling for background
      characteristics. The mediating effect of use of a physician's office or clinic as
      a source for routine care was tested. At each wave, between 18 and 20 % of
      mothers were considered as having moderate or severe depressive symptoms. These
      mothers were 1.3 percentage points more likely to put their infants to bed with a
      bottle, 2.6 percentage points less likely to have rules about the foods their
      children eat, and their children were 3.0 percentage points less likely to be in
      bed by 9:00 p.m. than mothers lacking depressive symptoms. These mothers also
      reported that their families ate dinner together fewer nights per week, and their
      children watched more television per day, than non-depressed mothers. The use of
      a physician's office or clinic partially mediated associations between maternal
      depressive symptoms and whether infants went to bed with a bottle. Interventions
      that identify maternal depression early may be useful in promoting healthy
      parenting behaviors and weight outcomes among young children.

PMID- 24077963
TI  - Boron neutron capture therapy (BNCT) for liver metastasis in an experimental
      model: dose-response at five-week follow-up based on retrospective dose
      assessment in individual rats.
AB  - Boron neutron capture therapy (BNCT) was proposed for untreatable colorectal
      liver metastases. Employing an experimental model of liver metastases in rats, we
      recently demonstrated that BNCT mediated by boronophenylalanine (BPA-BNCT) at 13
      Gy prescribed to tumor is therapeutically useful at 3-week follow-up. The aim of
      the present study was to evaluate dose-response at 5-week follow-up, based on
      retrospective dose assessment in individual rats. BDIX rats were inoculated with
      syngeneic colon cancer cells DHD/K12/TRb. Tumor-bearing animals were divided into
      three groups: BPA-BNCT (n = 19), Beam only (n = 8) and Sham (n = 7) (matched
      manipulation, no treatment). For each rat, neutron flux was measured in situ and
      boron content was measured in a pre-irradiation blood sample for retrospective
      individual dose assessment. For statistical analysis (ANOVA), individual data for
      the BPA-BNCT group were pooled according to absorbed tumor dose, BPA-BNCT I: 4.5
      8.9 Gy and BPA-BNCT II: 9.2-16 Gy. At 5 weeks post-irradiation, the tumor surface
      area post-treatment/pre-treatment ratio was 12.2 +/- 6.6 for Sham, 7.8 +/- 4.1
      for Beam only, 4.4 +/- 5.6 for BPA-BNCT I and 0.45 +/- 0.20 for BPA-BNCT II;
      tumor nodule weight was 750 +/- 480 mg for Sham, 960 +/- 620 mg for Beam only,
      380 +/- 720 mg for BPA-BNCT I and 7.3 +/- 5.9 mg for BPA-BNCT II. The BPA-BNCT II
      group exhibited statistically significant tumor control with no contributory
      liver toxicity. Potential threshold doses for tumor response and significant
      tumor control were established at 6.1 and 9.2 Gy, respectively.

PMID- 24077964
TI  - Deletion of SHP-2 in mesenchymal stem cells causes growth retardation, limb and
      chest deformity, and calvarial defects in mice.
AB  - In mice, induced global disruption of the Ptpn11 gene, which encodes the SHP-2
      tyrosine phosphatase, results in severe skeletal abnormalities. To understand the
      extent to which skeletal abnormalities can be attributed to perturbation of SHP-2
      function in bone-forming osteoblasts and chondrocytes, we generated mice in which
      disruption of Ptpn11 is restricted to mesenchymal stem cells (MSCs) and their
      progeny, which include both cell types. MSC-lineage-specific SHP-2 knockout (MSC
      SHP-2 KO) mice exhibited postnatal growth retardation, limb and chest deformity,
      and calvarial defects. These skeletal abnormalities were associated with an
      absence of mature osteoblasts and massive chondrodysplasia with a vast increase
      in the number of terminally differentiated hypertrophic chondrocytes in affected
      bones. Activation of mitogen activated protein kinases (MAPKs) and protein kinase
      B (PKB; also known as AKT) was impaired in bone-forming cells of MSC SHP-2 KO
      mice, which provides an explanation for the skeletal defects that developed.
      These findings reveal a cell-autonomous role for SHP-2 in bone-forming cells in
      mice in the regulation of skeletal development. The results add to our
      understanding of the pathophysiology of skeletal abnormalities observed in humans
      with germline mutations in the PTPN11 gene (e.g. Noonan syndrome and LEOPARD
      syndrome). 

PMID- 24077965
TI  - Molecular mechanism of sphingosine-1-phosphate action in Duchenne muscular
      dystrophy.
AB  - Duchenne muscular dystrophy (DMD) is a lethal muscle-wasting disease. Studies in
      Drosophila showed that genetic increase of the levels of the bioactive
      sphingolipid sphingosine-1-phosphate (S1P) or delivery of 2-acetyl-5
      tetrahydroxybutyl imidazole (THI), an S1P lyase inhibitor, suppresses dystrophic
      muscle degeneration. In the dystrophic mouse (mdx), upregulation of S1P by THI
      increases regeneration and muscle force. S1P can act as a ligand for S1P
      receptors and as a histone deacetylase (HDAC) inhibitor. Because Drosophila has
      no identified S1P receptors and DMD correlates with increased HDAC2 levels, we
      tested whether S1P action in muscle involves HDAC inhibition. Here we show that
      beneficial effects of THI treatment in mdx mice correlate with significantly
      increased nuclear S1P, decreased HDAC activity and increased acetylation of
      specific histone residues. Importantly, the HDAC2 target microRNA genes miR-29
      and miR-1 are significantly upregulated, correlating with the downregulation of
      the miR-29 target Col1a1 in the diaphragm of THI-treated mdx mice. Further gene
      expression analysis revealed a significant THI-dependent decrease in inflammatory
      genes and increase in metabolic genes. Accordingly, S1P levels and functional
      mitochondrial activity are increased after THI treatment of differentiating C2C12
      cells. S1P increases the capacity of the muscle cell to use fatty acids as an
      energy source, suggesting that THI treatment could be beneficial for the
      maintenance of energy metabolism in mdx muscles. 

PMID- 24077966
TI  - The unfolded protein response has a protective role in yeast models of classic
      galactosemia.
AB  - Classic galactosemia is a human autosomal recessive disorder caused by mutations
      in the GALT gene (GAL7 in yeast), which encodes the enzyme galactose-1-phosphate
      uridyltransferase. Here we show that the unfolded protein response pathway is
      triggered by galactose in two yeast models of galactosemia: lithium-treated cells
      and the gal7Delta mutant. The synthesis of galactose-1-phosphate is essential to
      trigger the unfolded protein response under these conditions because the deletion
      of the galactokinase-encoding gene GAL1 completely abolishes unfolded protein
      response activation and galactose toxicity. Impairment of the unfolded protein
      response in both yeast models makes cells even more sensitive to galactose,
      unmasking its cytotoxic effect. These results indicate that endoplasmic reticulum
      stress is induced under galactosemic conditions and underscores the importance of
      the unfolded protein response pathway to cellular adaptation in these models of
      classic galactosemia. 

PMID- 24077968
TI  - The iron-binding protein lactoferrin protects vulnerable dopamine neurons from
      degeneration by preserving mitochondrial calcium homeostasis.
AB  - Previous studies on postmortem human brain tissue have shown that the iron
      binding glycoprotein lactoferrin is upregulated in dopamine (DA) neurons
      resistant to degeneration in Parkinson disease (PD). To study how this could
      possibly relate to disease progression, we used midbrain cultures and
      experimental settings that model the progressive loss of DA neurons in this
      disorder. Human lactoferrin of either recombinant or natural origin provided
      robust protection to vulnerable DA neurons in a culture paradigm in which these
      neurons die spontaneously and selectively as they mature. The efficacy of
      lactoferrin was comparable to that of glial cell line-derived neurotrophic
      factor, a prototypical neurotrophic factor for DA neurons. Neuroprotection by
      lactoferrin was attributable to its binding to heparan sulfate proteoglycans on
      the cell surface of DA neurons and subsequently to partial inactivation of focal
      adhesion kinase (FAK), a major effector kinase of integrins. We established that
      FAK inactivation served to unmask a prosurvival phosphoinositide 3-kinase/AKT
      dependent signaling pathway that stimulates calcium shuttling from endoplasmic
      reticulum to mitochondria. DA neurons exposed to the mitochondrial toxin 1-methyl
      4-phenylpyridinium were also partially protected by lactoferrin, further
      supporting the view that mitochondria may represent a downstream target for
      lactoferrin protective actions. Finally, we found that the iron binding
      capability of lactoferrin intervened in DA cell rescue only when
      neurodegeneration was consecutive to iron-catalyzed oxidative stress. Overall,
      our data suggest that the accumulation of lactoferrin in PD brains might be
      evidence of an attempt by the brain to minimize the consequences of
      neurodegeneration. 

PMID- 24077967
TI  - Mechanism of action of novel lung edema therapeutic AP301 by activation of the
      epithelial sodium channel.
AB  - AP301 [Cyclo(CGQRETPEGAEAKPWYC)], a cyclic peptide comprising the human tumor
      necrosis factor lectin-like domain (TIP domain) sequence, is currently being
      developed as a treatment for lung edema and has been shown to reduce
      extravascular lung water and improve lung function in mouse, rat, and pig models.
      The current paradigm for liquid homeostasis in the adult mammalian lung is that
      passive apical uptake of sodium via the amiloride-sensitive epithelial Na+
      channel (ENaC) and nonselective cyclic-nucleotide-gated cation channels creates
      the major driving force for reabsorption of water through the alveolar epithelium
      in addition to other ion channels such as potassium and chloride channels. AP301
      can increase amiloride-sensitive current in A549 cells as well as in freshly
      isolated type II alveolar epithelial cells from different species. ENaC is
      expressed endogenously in all of these cell types. Consequently, this study was
      undertaken to determine whether ENaC is the specific target of AP301. The effect
      of AP301 in A549 cells as well as in human embryonic kidney cells and Chinese
      hamster ovary cells heterologously expressing human ENaC subunits (alpha, beta,
      gamma, and delta) was measured in patch clamp experiments. The congener TIP
      peptide AP318 [Cyclo(4-aminobutanoic acid-GQRETPEGAEAKPWYD)] activated ENaC by
      increasing single-channel open probability. AP301 increased current in
      proteolytically activated (cleaved) but not near-silent (uncleaved) ENaC in a
      reversible manner. alphabetagamma- or deltabetagamma-ENaC coexpression was
      required for maximal activity. No increase in current was observed after
      deglycosylation of extracellular domains of ENaC. Thus, our data suggest that the
      specific interaction of AP301 with both endogenously and heterologously expressed
      ENaC requires precedent binding to glycosylated extracellular loop(s).

PMID- 24077969
TI  - [National and international schizophrenia guidelines. Update 2013 regarding
      recommendations about antipsychotic pharmacotherapy].
AB  - Treatment guidelines provide evidence-based recommendations for diagnosis and
      treatment to assist clinicians, care givers and patients in finding an optimized
      treatment option in given clinical situations. Specific treatment guidelines for
      schizophrenia issued by the German Association of Psychiatry, Psychotherapy and
      Psychosomatics (DGPPN) and published under the auspices of the Working Group for
      Scientific Medical Specialist Societies (AWMF) (i.e. fulfilling the highest
      quality standards at the S3 level) have been available in Germany since 2006.
      Currently, a comprehensive revision process is ongoing to update these guidelines
      with the aim to publish the revision before 2014. However, since publication of
      the German treatment guidelines many clinical trials and meta-analyses have been
      published which appear to make a new evaluation of antipsychotic drug treatment
      necessary. Currently available national and international guidelines, such as the
      WFSBP, PORT and NICE guidelines, place less emphasis on the general superiority
      of atypical antipsychotic medication but support the idea to evaluate
      antipsychotic drugs based on the side effect profiles. The present overview
      discusses the recent guidelines development processes regarding schizophrenia and
      compares the available German treatment guidelines with recently published
      international guidelines. Current developments and issues for discussion are
      described in detail to provide possible implications for changes in treatment
      recommendations.

PMID- 24077971
TI  - Effectiveness of Mindfulness-Based Cognitive Therapy on the Quality of Life,
      Emotional Status, and CD4 Cell Count of Patients Aging with HIV Infection.
AB  - Long-term diagnosed and treated HIV-infected patients have to cope with a wide
      range of challenges that threaten their ability to age successfully. We report
      the results of a randomized controlled trial testing the effects of a mindfulness
      based cognitive therapy (MBCT) program on quality of life (QoL), emotional
      status, and immune status over a 3-month period. Forty HIV-infected patients
      diagnosed prior to 1996 and on cART for a minimum of 5 years were randomized to
      follow an MBCT program (n = 20) or remain as controls (routine follow-up) (n =
      20). A regression analysis was performed, and the measurement of effect size was
      estimated using Cohen's d. QoL, psychological stress, depressive symptoms, and
      anxiety symptoms improved in the MBCT group compared with the control group.
      During follow-up, patients in the MBCT group had a significantly increased CD4
      cell count. Effect sizes for MBCT on the variables assessed were large (d = 0.8).
      The findings suggest that this program may help to promote successful aging in
      these patients.

PMID- 24077970
TI  - Cognitive and field testing of a new set of medication adherence self-report
      items for HIV care.
AB  - We conducted four rounds of cognitive testing of self-report items that included
      66 sociodemographically diverse participants, then field tested the three best
      items from the cognitive testing in a clinic waiting room (N = 351) and in an
      online social networking site for men who have sex with men (N = 6,485). As part
      of the online survey we conducted a randomized assessment of two versions of the
      adherence questionnaire-one which asked about adherence to a specific
      antiretroviral medication, and a second which asked about adherence to their "HIV
      medicines" as a group. Participants were better able to respond using adjectival
      and adverbial scales than visual analogue or percent items. The internal
      consistency reliability of the three item adherence scale was 0.89. Mean scores
      for the two different versions of the online survey were similar (91.0 vs. 90.2,
      p < 0.05), suggesting that it is not necessary, in general, to ask about
      individual medications in an antiretroviral therapy regimen when attempting to
      describe overall adherence.

PMID- 24077972
TI  - Correlates of HIV infection among African American women from 20 cities in the
      United States.
AB  - Little research has been conducted to investigate multiple levels of HIV risk
      individual risk factors, sex partner characteristics, and socioeconomic factors
      among African American women, who, in 2010, comprised 64 % of the estimated 9,500
      new infections in women. Respondent-driven sampling was used to recruit and
      interview women in 20 cities with high AIDS prevalence in the United States
      through the National HIV Behavioral Surveillance System. We assessed individual
      risk factors, sex partner characteristics, and socioeconomic characteristics
      associated with being HIV-positive but unaware of the infection among African
      American women. Among 3,868 women with no previous diagnosis of HIV, 68 % had
      high school education or more and 84 % lived at or below the poverty line. In
      multivariable analysis, women who were 35 years or older, homeless, received
      Medicaid, whose last sex partner ever used crack cocaine or was an exchange sex
      partner were more likely to be HIV-positive-unaware. Developing and implementing
      strategies that address socioeconomic factors, such as homelessness and living in
      poverty, as well as individual risk factors, can help to maximize the
      effectiveness of the public health response to the HIV epidemic.

PMID- 24077973
TI  - Comparing Estimates of Multiple and Concurrent Partnerships Across Population
      Based Surveys: Implications for Combination HIV Prevention.
AB  - We compare estimates of multiple and concurrent sexual partnerships from
      Demographic and Health Surveys (DHS) with comparable Population Services
      International (PSI) surveys in four African countries (Kenya, Lesotho, Uganda,
      Zambia). DHS data produce significantly lower estimates of all indicators for
      both sexes in all countries. PSI estimates of multiple partnerships are 1.7 times
      higher [1.4 for men (M), 3.0 for women (W)], cumulative prevalence of concurrency
      is 2.4 times higher (2.2 M, 2.7 W), the point prevalence of concurrency is 3.5
      times higher (3.5 M, 3.3 W), and the fraction of multi-partnered persons who
      report concurrency last year is 1.4 times higher (1.6 M, 0.9 W). These findings
      provide strong empirical evidence that DHS surveys systematically underestimate
      levels of multiple and concurrent partnerships. The underestimates will
      contaminate both empirical analyses of the link between sexual behavior and HIV
      infection, and theoretical models for combination prevention that use these data
      for inputs.

PMID- 24077974
TI  - Virtual versus physical spaces: which facilitates greater HIV risk taking among
      men who have sex with men in East and South-East Asia?
AB  - Increasing use of the Internet to seek sex partners is accompanied by rising HIV
      infections among men who have sex with men (MSM) in East and South-East Asia. We
      examined whether the Internet facilitates greater HIV risk taking among MSM in
      the region. A cross-sectional sample of 9,367 MSM was recruited via the Internet
      in 2010. We compared socio-demographic and HIV-related behavioral characteristics
      among MSM who met sex partners on the Internet only, who met sex partners offline
      only, and who met sex partners through both. Multinomial logistic regression was
      used to identify independent correlates that were associated with differences in
      where participants met their male sex partners. Compared to MSM who met partners
      offline only, those who met partners online only were less likely to have
      multiple male sex partners, have paid for sex, have consumed recreational drugs,
      and have used alcohol before sex. MSM who met partners both online and offline
      appeared to be the riskiest group that they were more likely to have multiple
      male sex partners, have engaged in UIAI, and have consumed alcohol before sex.
      These findings suggest that social networking websites alone do not facilitate
      greater HIV risk taking among MSM. Rather, they provide additional venues for MSM
      who already engage in HIV-related high risk behaviors to seek sex partners. The
      Internet offers incredible opportunities to reach large numbers of MSM in East
      and South-East Asia for HIV prevention and research. Web-based outreach and
      prevention activities are needed to reach these men. In addition, mobile and
      application-based interventions should also be developed and disseminated.

PMID- 24077975
TI  - Attitude and behavior changes among gay and bisexual men after use of rapid home
      HIV tests to screen sexual partners.
AB  - HIV testing can now be self-administered outside clinical settings through the
      purchase of home testing (HT) kits. Individuals also can use the kits to perform
      a test on a potential sexual partner prior to intercourse. We provided a 3-month
      supply of HT kits to men who reported multiple male partners and little or no
      condom use for anal intercourse. Participants used the test kits with partners in
      over 100 occasions. At the end of the study, approximately half of the
      participants described shifts in their attitudes and/or behaviors related to
      sexual risk. Reported changes included increased awareness of risk, increased
      discussion of STI/HIV safety measures, changes in partner choice and heightened
      consciousness of partner thinking. Easy access to HT kits may be a risk-reduction
      strategy for men with a high risk profile because their regular use could have an
      impact beyond the specific sexual encounter.

PMID- 24077977
TI  - Clinical characteristics of children with positive anti-SSA/SSB  antibodies.
AB  - This study aimed to characterize the manifestations of clinical symptoms and
      signs, primary rheumatic diseases, and other autoantibodies in pediatric patients
      with positive anti-SSA and/or anti-SSB antibodies. Subjects under age 18 with
      positive anti-SSA and/or anti-SSB antibodies were screened and enrolled in a
      tertiary hospital in Taiwan. Data were collected via medical records,including
      age, gender, onset of the primary rheumatic disease, clinical symptoms and signs,
      and the medication used. Schirmer test for Sjogren's syndrome (SS) screening was
      performed in all enrolled patients. Among twenty enrolled subjects, seventeen of
      them had systemic lupus erythematosus; four of them were diagnosed as SS with
      positive Schirmer test. In addition to antinuclear antibodies and anti-DNA
      antibodies, other common autoantibodies were anti-RNP antibodies (50 %) and anti
      Sm antibodies(30 %). The most common symptoms were arthritis (60 %)followed by
      malar rash (40 %). In conclusion, we observed that a low proportion of childhood
      SS (4/20) exists in our patients with positive SSA and/or anti-SSB antibodies. It
      is suggested that clinicians should focus more on the clinical symptoms in these
      patients, rather than undertaking invasive diagnostic interventions to rule out
      Sjogren's syndrome.

PMID- 24077978
TI  - A critical assessment of the endocrine susceptibility of the human testis to
      phthalates from fetal life to adulthood.
AB  - BACKGROUND: A very large proportion of the literature on the endocrine disruptors
      categorized as anti-androgens deals with phthalates, which are produced in large
      amounts for use as plastic emollients and additives. In this review, we bring
      together and analyse work on the effects of phthalates in animals and humans at
      different stages of their development to assess whether or not their possible
      anti-androgenic properties represent a significant threat to human health.
      METHODS: The database PubMed was systematically searched for all English language
      articles until July 2013 in each subject area discussed. RESULTS: We provide an
      up-to-date exhaustive, comparative and critical assessment of both in vivo and in
      vitro studies undertaken to explore the effects of phthalates on the human testis
      from fetal life to adulthood. These results are compared and discussed in the
      light of the key data reported in the literature for mice and rats. CONCLUSIONS:
      The current literature highlights the fact that (i) there is a huge difference
      between the number of studies performed in animals and in humans, with many fewer
      for humans; (ii) there are differences in the way rats, mice, primates and humans
      respond to phthalates, for reasons that need to be further explored; (iii) more
      work is required to clarify the contradictions, in the few existing human
      epidemiological studies at all stages of development, which may be partly
      explained by varying methods of exposure assessment; (iv) in accordance with
      recent findings in rodents, it cannot be excluded that transgenerational effects
      of phthalates and/or epigenetic changes exist in humans; (v) a number of
      methodological limitations need to be solved for the in vitro and xenografting
      models using human fetal testis to fulfil their 'missing link' role between
      epidemiological studies in humans and rodent models; and (vi) epidemiological and
      in vitro studies generally converge sufficiently to conclude that phthalate anti
      androgenicity is plausible in adult men.

PMID- 24077980
TI  - Individualization of controlled ovarian stimulation in IVF using ovarian reserve
      markers: from theory to practice.
AB  - BACKGROUND: The main objective of individualization of treatment in IVF is to
      offer every single woman the best treatment tailored to her own unique
      characteristics, thus maximizing the chances of pregnancy and eliminating the
      iatrogenic and avoidable risks resulting from ovarian stimulation.
      Personalization of treatment in IVF should be based on the prediction of ovarian
      response for every individual. The starting point is to identify if a woman is
      likely to have a normal, poor or a hyper response and choose the ideal treatment
      protocol tailored to this prediction. The objective of this review is to
      summarize the predictive ability of ovarian reserve markers, such as antral
      follicle count (AFC) and anti-Mullerian hormone (AMH), and the therapeutic
      strategies that have been proposed in IVF after this prediction. METHODS: A
      systematic review of the existing literature was performed by searching Medline,
      EMBASE, Cochrane library and Web of Science for publications in the English
      language related to AFC, AMH and their incorporation into controlled ovarian
      stimulation (COS) protocols in IVF. Literature available to May 2013 was
      included. RESULTS: The search generated 305 citations of which 41 and 25 studies,
      respectively, reporting the ability of AMH and AFC to predict response to COS
      were included in this review. The literature review demonstrated that AFC and
      AMH, the most sensitive markers of ovarian reserve identified to date, are ideal
      in planning personalized COS protocols. These sensitive markers permit prediction
      of the whole spectrum of ovarian response with reliable accuracy and clinicians
      may use either of the two markers as they can be considered interchangeable.
      Following the categorization of expected ovarian response to stimulation
      clinicians can adopt tailored therapeutic strategies for each patient. Current
      scientific trend suggests the elective use of the GnRH antagonist based regimen
      for hyper-responders, and probably also poor responders, as likely to be
      beneficial. The selection of the appropriate and individualized gonadotrophin
      dose is also of paramount importance for effective COS and subsequent IVF
      outcomes. CONCLUSION: Personalized IVF offers several benefits; it enables
      clinicians to give women more accurate information on their prognosis thus
      facilitating counselling especially in cases of extremes of ovarian response. The
      deployment of therapeutic strategies based on selective use of GnRH analogues and
      the fine tuning of the gonadotrophin dose on the basis of potential ovarian
      response in every single woman can allow for a safer and more effective IVF
      practice.

PMID- 24077981
TI  - Multicenter phase II study of oxaliplatin and sorafenib in advanced gastric
      adenocarcinoma after failure of cisplatin and fluoropyrimidine treatment. A
      GEMCAD study.
AB  - BACKGROUND: Cisplatin and fluoropyrimidine (CF) are standard first- line
      treatment in advanced gastric cancer, but no second-line treatment has yet been
      established. We present a phase II study in which we evaluated the efficacy and
      toxicity of the combination of Sorafenib (S), and Oxaliplatin as second-line
      therapy. METHODS: Patients with progressive gastric adenocarcinoma after CF-
      first-line, ECOG 0-2, and measurable disease were included. The primary objective
      was PFS. Treatment doses were Oxaliplatin 130 mg/m2/3 weeks and Sorafenib 800
      mg/bid/d. RESULTS: We included 40 patients. CR was 2.5% and SD was 47.2%. Grade 3
      4 toxic effects were neutropenia (9.8%), thrombocytopenia (7.3%), neurotoxicity
      (4.9%) and diarrhea (4.9%). Median PFS was 3 months (95%CI: 2.3-4.1) and median
      OS was 6.5 months (95% CI: 5.2-9.6). Time to progression (TTP) to first line
      therapy was a prognosis factor. Median OS was 9.7 months when time-to-progression
      during first-line chemotherapy was >6 months and 5.6 m when it was <6 months (p =
      0.04). CONCLUSIONS: Time-to-progression under a CF-based first-line therapy
      determines subgroups of GC patients with different prognosis. The combination of
      Oxaliplatin-Sorafenib in advanced GC patients previously treated with CF appears
      safe, but our results do not support the implementation of a phase III trial.

PMID- 24077982
TI  - A phase I, dose-escalation study of the Eg5-inhibitor EMD 534085 in patients with
      advanced solid tumors or lymphoma.
AB  - BACKGROUND: The kinesin spindle protein Eg5 is involved in mitosis, and its
      inhibition promotes mitotic arrest. EMD 534085, a potent, reversible Eg5
      inhibitor, demonstrated significant preclinical antitumor activity. METHODS: This
      first-in-man, single-center, open-label, phase I dose-escalation study (3 + 3
      design) investigated EMD 534085 safety, pharmacokinetics and antitumor activity
      in refractory solid tumors, Hodgkin's lymphoma, or non-Hodgkin's lymphoma. EMD
      534085 (starting dose 2 mg/m2/day) was administered intravenously every 3 weeks.
      Doses were escalated in 100% steps in successive cohorts of 3 patients until
      grade 2 toxicity occurred, followed by 50% until the first dose-limiting toxicity
      (DLT) arose. If <2 of 6 patients experienced a DLT, doses were further increased
      by 25%. Dose-escalation was stopped if a DLT occurred in >=2 of 6 patients.
      RESULTS: Forty-four patients received EMD 534085. Median treatment duration was
      43 days (range, 21-337). Thirty-eight patients (86%) received >=2 cycles. DLTs
      were grade 4 neutropenia (1 patient each at 108 and 135 mg/m2/day), and grade 3
      acute coronary syndrome with troponin I elevation (1 patient at 135 mg/m2/day).
      The maximum tolerated dose (MTD) was 108 mg/m2/day. The most common treatment
      related adverse events were asthenia (50%) and neutropenia (32%). EMD 534085
      appeared to have linear pharmacokinetics. Increase in phospho-histone H3 positive
      cells in paired pre- and on-treatment biopsies showed evidence of target
      modulation. No complete or partial responses were observed. Best response was
      stable disease in 23 patients (52%). CONCLUSIONS: EMD 534085 appeared to be well
      tolerated; MTD was 108 mg/m2/day. Preliminary antitumor results suggested limited
      activity in monotherapy.

PMID- 24077984
TI  - Optimisation of Downscaled Tandem Affinity Purifications to Identify Core Protein
      Complexes.
AB  - In this study we show that via stable, retroviral-expression of tagged EGFR del
      (L747-S752 deletion mutant) in the PC9 lung cancer cell line and stable
      doxycycline-inducible expression of tagged Grb2 using a Flp-mediated
      recombination HEK293 cell system, the SH-TAP can be downscaled to 5 to 12.5 mg
      total protein input (equivalent to 0.5 - 1 * 15 cm culture plate or 4 - 8 * 106
      cells). The major constituents of the EGFR del complex (USB3B, GRB2, ERRFI,
      HSP7C, GRP78, HSP71) and the Grb2 complex (ARHG5, SOS1, ARG35, CBL, CBLB, PTPRA,
      SOS2, DYN2, WIPF2, IRS4) were identified. Adjustment of the quantity of digested
      protein injected into the mass spectrometer reveals that optimisation is required
      as high quantities of material led to a decrease in protein sequence coverage and
      the loss of some interacting proteins. This investigation should aid other
      researchers in performing tandem affinity purifications in general, and in
      particular, from low quantities of input material.

PMID- 24077985
TI  - The association of gestational weight gain with birth weight in obese pregnant
      women by obesity class and diabetic status: a population-based historical cohort
      study.
AB  - Small-for-gestational-age (SGA) and large-for gestational-age (LGA) infants are
      associated with increased adverse outcomes. While studies have estimated the
      association of gestational weight gain with birth weight in obese women,
      estimates are lacking by obesity class and diabetic status. A population-based
      historical cohort study of 66,010 obese pregnant women in Missouri delivering
      liveborn, singleton, term infants in 2002-2008 was conducted. Adjusted odds
      ratios for SGA and LGA infants were calculated for gestational weight gain
      categories with multiple logistic regression using the revised Institute of
      Medicine(IOM) recommended 11-20 pounds as the reference group. A weight gain of 3
      10 pounds was not significantly associated with an increased risk of an SGA
      infant compared to 11-20 pounds in 5/6 obesity class/diabetic status
      combinations.The exception was Class I Obese non-diabetic women(adjusted odds
      ratio = 1.28, 95 % confidence interval 1.07, 1.52). When lower amounts of weight
      gain were considered, diabetic women who gained <=2 pounds (including women who
      lost weight) did not have a significantly increased risk of an SGA infant
      compared to diabetic women who gained 11-20 pounds in any obesity class. Weight
      gains less than 11-20 pounds were significantly associated with a decreased risk
      of an LGA infant in 5/6 obesity class/diabetic status combinations. Weight gains
      lower than the IOM recommendation of 11-20 pounds during pregnancy for obese
      women generally were significantly associated with decreased risk of LGA infants
      without being significantly associated with increased risk of SGA infants and
      differed by obesity class and diabetic status.

PMID- 24077979
TI  - The role of angiogenic factors in fibroid pathogenesis: potential implications
      for future therapy.
AB  - BACKGROUND: It is well established that tumors are dependent on angiogenesis for
      their growth and survival. Although uterine fibroids are known to be benign
      tumors with reduced vascularization, recent work demonstrates that the
      vasculature of fibroids is grossly and microscopically abnormal. Accumulating
      evidence suggests that angiogenic growth factor dysregulation may be implicated
      in these vascular and other features of fibroid pathophysiology. METHODS:
      Literature searches were performed in PubMed and Google Scholar for articles with
      content related to angiogenic growth factors and myometrium/leiomyoma. The
      findings are hereby reviewed and discussed. RESULTS: Multiple growth factors
      involved in angiogenesis are differentially expressed in leiomyoma compared with
      myometrium. These include epidermal growth factor (EGF), heparin-binding-EGF,
      vascular endothelial growth factor, basic fibroblast growth factor, platelet
      derived growth factor, transforming growth factor-beta and adrenomedullin. An
      important paradox is that although leiomyoma tissues are hypoxic, leiomyoma
      feature down-regulation of key molecular regulators of the hypoxia response.
      Furthermore, the hypoxic milieu of leiomyoma may contribute to fibroid
      development and growth. Notably, common treatments for fibroids such as GnRH
      agonists and uterine artery embolization (UAE) are shown to work at least partly
      via anti-angiogenic mechanisms. CONCLUSIONS: Angiogenic growth factors play an
      important role in mechanisms of fibroid pathophysiology, including abnormal
      vasculature and fibroid growth and survival. Moreover, the fibroid's abnormal
      vasculature together with its aberrant hypoxic and angiogenic response may make
      it especially vulnerable to disruption of its vascular supply, a feature which
      could be exploited for treatment. Further experimental studies are required in
      order to gain a better understanding of the growth factors that are involved in
      normal and pathological myometrial angiogenesis, and to assess the potential of
      anti-angiogenic treatment strategies for uterine fibroids.

PMID- 24077986
TI  - Learning to Use an Alphabetic Writing System.
AB  - Gaining facility with spelling is an important part of becoming a good writer.
      Here we review recent work on how children learn to spell in alphabetic writing
      systems. Statistical learning plays an important role in this process. Thus,
      young children learn about some of the salient graphic characteristics of written
      texts and attempt to reproduce these characteristics in their own productions
      even before they use letters to represent phonemes. Later, children apply their
      statistical learning skills to links between phonemes and spellings, including
      those that are conditioned by context and morphology. Children use what they know
      about language and about letter names when learning about spelling, and learning
      to spell in turn influences their ideas about language. Although children learn
      about some aspects of spelling implicitly, explicit instruction has an important
      role to play. We discuss some implications of the research for the design of that
      instruction.

PMID- 24077983
TI  - Genetic influences on brain developmental trajectories on neuroimaging studies:
      from infancy to young adulthood.
AB  - Human brain development has been studied intensively with neuroimaging. However,
      little is known about how genes influence developmental brain trajectories, even
      though a significant number of genes (about 10,000, or approximately one-third)
      in the human genome are expressed primarily in the brain and during brain
      development. Interestingly, in addition to showing differential expression among
      tissues, many genes are differentially expressed across the ages (e.g.,
      antagonistic pleiotropy). Age-specific gene expression plays an important role in
      several critical events in brain development, including neuronal cell migration,
      synaptogenesis and neurotransmitter receptor specificity, as well as in aging and
      neurodegenerative disorders (e.g., Alzheimer disease or amyotrophic lateral
      sclerosis). In addition, the majority of psychiatric and mental disorders are
      polygenic, and many have onsets during childhood and adolescence. In this review,
      we summarize the major findings from neuroimaging studies that link genetics with
      brain development, from infancy to young adulthood. Specifically, we focus on the
      heritability of brain structures across the ages, age-related genetic influences
      on brain development and sex-specific developmental trajectories.

PMID- 24077987
TI  - Happy, 'healthy' and enjoying life on dialysis: an elderly perspective.

PMID- 24077988
TI  - Calcular pulmonary embolism.
AB  - Many complications of percutaneous nephrolithotomy(PNL) were reported. In this
      report, we present a rare complication, which has never been reported. It is the
      migration of stone fragments into the venous system causing pulmonary emboli. We
      reviewed the literatures reporting complications following PNL, and there was no
      available previous report about such complication. It was suspected
      intraoperative and confirmed radiologically postoperative. In this case,
      pulmonary emboli have had no clinical consequences and were managed
      conservatively.

PMID- 24077989
TI  - Relative CO2/NH3 permeabilities of human RhAG, RhBG and RhCG.
AB  - Mammalian glycosylated rhesus (Rh) proteins include the erythroid RhAG and the
      nonerythroid RhBG and RhCG. RhBG and RhCG are expressed in multiple tissues,
      including hepatocytes and the collecting duct (CD) of the kidney. Here, we
      expressed human RhAG, RhBG and RhCG in Xenopus oocytes (vs. H2O-injected control
      oocytes) and used microelectrodes to monitor the maximum transient change in
      surface pH (DpHS) caused by exposing the same oocyte to 5 % CO2/33 mM HCO3- (an
      increase) or 0.5 mM NH3/NH4+ (a decrease). Subtracting the respective values for
      day-matched, H2O-injected control oocytes yielded channel-specific values (*).
      (DeltapH*(S))(CO2) and (-DeltapH*(S))(NH3) were each significantly >0 for all
      channels, indicating that RhBG and RhCG--like RhAG--can carry CO2 and NH3. We
      also investigated the role of a conserved aspartate residue, which was reported
      to inhibit NH3 transport. However, surface biotinylation experiments indicate the
      mutants RhBG(D178N) and RhCG(D177N) have at most a very low abundance in the
      oocyte plasma membrane. We demonstrate for the first time that RhBG and RhCG-
      like RhAG--have significant CO2 permeability, and we confirm that RhAG, RhBG and
      RhCG all have significant NH3 permeability. However, as evidenced by
      (DeltapH*(S))(CO2)/ (-DeltapH*(S))(NH3) values, we could not distinguish among
      the CO2/ NH3 permeability ratios for RhAG, RhBG and RhCG. Finally, we propose a
      mechanism whereby RhBG and RhCG contribute to acid secretion in the CD by
      enhancing the transport of not only NH3 but also CO2 across the membranes of CD
      cells.

PMID- 24077990
TI  - Mitochondrial DNA analysis of Swedish population samples.
AB  - As a contribution to the geographic coverage of EMPOP, currently the best
      available forensic mitochondrial DNA (mtDNA) database, a total of 299 Swedish
      individuals were analysed by sequencing of the first and second hypervariable
      regions of the mtDNA genome. In this sample set, a total of 179 different
      haplotypes were detected. The genetic diversity was estimated to be 0.9895 (+/
      0.0023), and the random match probability was 1.39 %. The most abundant
      haplogroups were HV (including its subhaplogroups H andV) with a frequency of
      46.5%, followed by haplogroup U(including its subhaplogroup K) at 27.8 %,
      haplogroup T at 10.0 % and haplogroup J at 7.0 %, a distribution that is
      consistent with previous observations in other European populations.

PMID- 24077991
TI  - Psychomotor developmental delay and epilepsy in an offspring  of father-daughter
      incest: quantification of the causality  probability.

PMID- 24077992
TI  - Diapause-specific gene expression in Calliphora vicina (Diptera: Calliphoridae)-
      a useful diagnostic tool for forensic entomology.
AB  - Estimating the post mortem interval (PMImin) by age determination of blow fly
      larvae has been well-established for moderate temperatures. Low-temperature
      developmental data is only available sparsely and usually does not take
      overwintering strategies into account. The blow fly Calliphora vicina hibernates
      by diapausing in the third larval stage extending the duration of this
      developmental stage up to several weeks or even months. As the diagnosis of the
      diapause status is not possible by morphological characteristics, PMImin
      estimations might be biased during the cold season if only based on age
      determination of third instar larvae of C. vicina. Molecular markers were
      searched for which allows one to identify diapause in larvae. Expression analysis
      of 19 genes was performed in diapausing and non-diapausing larvae. Three genes
      encoding for heat shock proteins (hsp23, hsp24 and hsp70) were found to be up
      regulated distinctly in diapausing larvae and at 1 day in non-diapausing larvae.
      If several larvae are subjected to an analysis, a high variance in the expression
      level of the gene encoding for the anterior fat body protein is a further marker
      for diapause. The present study proves the potential use of gene expression
      analysis as a suitable diagnosis tool for diapause in C. vicina. 

PMID- 24077993
TI  - Regeneration of the limb: opinions on the reality.
AB  - Whenever the topic of re-growing human limbs is posed for discussion, it is often
      argued that 'if a newt can do it, then so can we'. This notion, albeit promising,
      is somewhat like watching a science-fiction film; the individual components are
      currently available but we are far from realizing the complete picture. Today's
      reality is that if we are faced with a limb-severing injury, any regenerative
      attempt would endeavour to accelerate the pace at which the tissue heals to a
      clinically relevant/functional state. The science of limb regeneration can be
      approached from three different angles, developmental biology; regenerative
      medicine; and tissue engineering. This opinion piece describes how each approach
      can be used to understand the concepts behind regeneration, how far each approach
      has advanced and the hurdles faced by each of the approaches.

PMID- 24077994
TI  - Can we regrow a human arm? A negative perspective from an upper-limb surgeon.
AB  - If we would like to devote time and money to the task of regrowing a human arm,
      we should feel free to do it, in principle. However, if we recognize a purpose in
      biomedical research, we must scrutinize this task in the light of a possible
      clinical application. We will then discover that regrowing a human arm is not
      only likely to be not possible, but also not required in the clinic. Bionic arms
      and better reconstructive surgery already provide a different, simpler and easier
      solution to the loss of a human arm, and should be promoted. Probably, ''can we
      regrow a human arm?'' is not the right question. Instead, we should ask, ''can we
      restore the function of a lost human arm?''.

PMID- 24077996
TI  - Nanoclays reinforced glass ionomer cements: dispersion and interaction of polymer
      grade (PG) montmorillonite with poly(acrylic acid).
AB  - Montmorillonite nanoclays (PGV and PGN) were dispersed in poly(acrylic acid)
      (PAA) for utilization as reinforcing filler in glass ionomer cements (GICs).
      Chemical and physical interaction of PAA and nanoclay (PGV and PGN) was studied.
      PAA-PGV and PAA-PGN solutions were prepared in different weight percent loadings
      of PGV and PGN nanoclay (0.5-8.0 wt%) via exfoliation-adsorption method.
      Characterization was carried out by X-ray diffraction (XRD), X-ray photoelectron
      spectroscopy (XPS) and fourier transform infrared (FTIR) spectroscopy. XRD
      results of PAA-PGN demonstrated that the interlayer space expanded from 12.83 to
      16.03 A indicating intercalation whereas the absence of the peak at d(001) in PAA
      PGV indicated exfoliation. XPS scans of PGV and PGN nanoclays depicted the main
      peak of O 1s photoelectron due to Si-O-M (M = Mg, Al, Fe) whereas, Si-O-Al
      linkages were identified by Si 2p or Si 2s and Al 2p or Al 2s peaks. The
      disappearance of the Na peak confirmed that PAA molecules exchanged sodium ions
      present on surface of silicate layers and significantly reduced the electrostatic
      van-der-Waals forces between silicate plates resulting in intercalation or
      exfoliation. FTIR spectra of PAA-nanoclay suspensions demonstrated the presence
      of a new peak at 1,019 cm(-1) associated with Si-O- stretching vibrations which
      increased with increasing nanoclays concentration. Information concerning the
      dispersion of nanoclay in PAA aqueous solutions, chemical reaction and increase
      interlayer space in montmorillonite nanoclay is particularly useful regarding
      dispersion and reinforcement of nanoclay in PAA.

PMID- 24077995
TI  - Promising perspectives towards regrowing a human arm.
AB  - Despite the great enthusiasm about tissue engineering during the 1980s and the
      many significant basic observations made since then, the clinical application of
      tissue-engineered products has been limited. However, the prospect of creating
      new human tissues and organs is still exciting and continues to be a significant
      challenge for scientists and clinicians. A human arm is an extremely complicated
      biological construction. Considering regrowing a human arm requires asking about
      the current state-of-the-art of tissue engineering and the real capabilities that
      it may offer within a realistic time horizon. This work briefly addresses the
      state-of-the-art in the fields of cells and scaffolds that have high regenerative
      potential. Additional tools that are required to reconstruct more complex parts
      of the body, such as a human arm, seem achievable with the already available more
      sophisticated culture systems including three-dimensional organization, dynamic
      conditions and co-cultures. Finally, we present results on cell differentiation
      and cell and tissue maturation in culture when cells are exposed to mechanical
      forces. We postulate that in the foreseeable future even such complicated
      structures such as a human arm will be regrown in full in vitro under the
      conditions of a mechanically controlled co-culture system.

PMID- 24077997
TI  - Diagnostic value of 18F-FDG PET/CT for lymph node metastasis of esophageal
      squamous cell carcinoma.
AB  - PURPOSE: This study investigated the diagnostic accuracy of hybrid positron
      emission tomography/computed tomography (PET/CT) for lymph node (LN) metastasis
      of esophageal cancer. We also investigated the correlation between the size of
      metastatic nests and the detection by PET/CT. METHODS: Two hundred and fifty
      eight patients with esophageal squamous cell carcinoma who underwent
      esophagectomy with two- or three-field radical lymphadenectomy were analyzed
      retrospectively. We compared the diagnosis of preoperative PET/CT to the
      postoperative histopathological examination by each anatomical field (n = 1,231)
      in all 258 patients. The metastatic LNs resected from PET/CT positive fields were
      classified as belonging to the PET/CT-N-positive group (n = 229) and those from
      negative fields as belonging to the PET/CT-N-negative group (n = 352). The cross
      sectional areas of metastatic nests were measured in each metastatic LN. RESULTS:
      Of the 1,231 fields, 275 (22 %) were positive for metastasis, including 581 LNs
      from 408 regional LN stations. The sensitivity and specificity of PET/CT examined
      by each anatomical field were 25.8 and 97.8 %, respectively. The median area of
      metastatic nests was 17.7 mm2 in the PET/CT-N-positive group, and 7.7 mm2 in the
      PET/CT-N-negative group (p < 0.001). CONCLUSIONS: A significant correlation was
      suggested between the nest size and detection by PET/CT. Because of its low
      sensitivity, PET/CT alone is insufficient to determine the surgical procedures,
      especially when considering reduction surgery.

PMID- 24077998
TI  - Interim report of the Japanese original donor evaluation and management system:
      the medical consultant system.
AB  - PURPOSE: Lung transplantation (LTx) is an established therapy for end-stage lung
      failure. However, in Japan, the donor organ shortage is extremely severe compared
      with other developed countries, because of the strict Japanese Organ
      Transplantation Law. To maximize LTx opportunities in Japan, we have established
      a special donor evaluation and management system termed the medical consultant
      (MC) system. METHODS: Data from 171 lung donor candidates registered in Japan
      from May 1998 to May 2012 were obtained and investigated in a retrospective
      manner. The candidates were separated into the non-MC-intervened and MC
      intervened groups, and then data regarding the PaO2/FiO2 ratio, donation rate and
      organ survival rate were analyzed and compared between the groups. RESULTS: The
      PaO2/FiO2 ratio of the MC-intervened group was ameliorated from the time of first
      brain death diagnosis to organ harvest. Although the base condition of the MC
      intervened group was significantly worse than that of the non-MC-intervened
      group, the donation rates showed no significant difference (0.64 and 0.66,
      respectively; p = 0.89). There was a difference in the organ survival rate
      between the non-MC and MC-intervened groups (5-year survival rates of 67.2 and
      88.3 %, respectively; p = 0.16). CONCLUSION: The MC system used for organ donor
      evaluation and management in Japan has achieved acceptable interim results.

PMID- 24077999
TI  - Prognostic factors for peritoneal carcinomatosis originating  from colorectal
      cancer: an analysis of 921 patients  from a multi-institutional database.
AB  - PURPOSE: The purpose of this study was to clarify the factors affecting R0
      resection and the prognosis of patients with peritoneal carcinomatosis (PC) from
      colorectal cancer (CRC) in the Japanese population. METHODS: A multi
      institutional retrospective analysis of 921 patients who underwent surgery
      between 1991 and 2007 for CRC with PC was conducted. Clinicopathological
      variables were analyzed for prognostic significance. A multivariate analysis
      using a Cox regression modeling was performed to assess the prognostic value of
      the variables. RESULTS: The median survival time of all patients was 14.3 months
      (range 0-209 months) and the 5-year overall survival rate was 9.7%. The
      multivariate analysis revealed that a lymph node status of pN0/1, the absence of
      blood-born metastasis, R0 resection and adjuvant chemotherapy favorably affected
      the survival. Furthermore, the completion of R0 resection was significantly
      affected by the preoperative serum CEA level, the presence of blood-born
      metastasis and the grade of PC. The 5-year overall survival and median survival
      time of the patients with four favorable prognostic factors, namely pN0/1, the
      absence of blood-born metastasis, R0 resection and adjuvant chemotherapy, were
      significantly better than those of the remaining patients (37.1 vs. 7.2% and 37.0
      vs. 13.3 months, respectively; p < 0.0001). CONCLUSIONS: Although few patients
      with PC from CRC survive for more than 5 years, performing R0 resection with
      curative intent in association with postoperative adjuvant chemotherapy should be
      considered in appropriately selected patients.

PMID- 24078001
TI  - Sciatic hernia: is it really rare?
AB  - PURPOSE: It is generally believed that sciatic hernia is extremely rare; however,
      asymptomatic sciatic hernia is occasionally found in patients with an obturator
      hernia. We investigated the frequency, risk factors, and prognosis of
      asymptomatic sciatic hernia, which have never been discussed in a published
      report. METHODS: We retrospectively reviewed multidetector-row computed
      tomography (MDCT) images of 38 consecutive cases of new-onset obturator hernia.
      The co-existence of sciatic hernia was diagnosed from the MDCT findings of some
      of these patients. The clinical characteristics and clinical courses were
      compared between the sciatic hernia group and the non-sciatic hernia group.
      RESULTS: Nine patients (24 %) had concomitant asymptomatic sciatic hernias, five
      (13 %) of which were bilateral.The body mass index (BMI) was significantly lower
      in the patients with a concomitant sciatic hernia (17.2 +/- 2.4 kg/m(2)) than in
      those without a sciatic hernia (19.6 +/- 2.6 kg/m(2); P = 0.02). All patients
      received treatment for incarcerated obturator hernias, but none underwent repair
      of the concomitant sciatic hernia because all were non-incarcerated and
      asymptomatic. None of the patients has had trouble with their untreated sciatic
      hernia after the obturator hernia treatment. CONCLUSIONS: Up to 24 % of these
      obturator hernia patients had a concomitant sciatic hernia. A low BMI was a risk
      factor for concomitant sciatic hernia. Immediate surgical repair of the sciatic
      hernia may not be needed, unless it is symptomatic.

PMID- 24078000
TI  - Ischemia-reperfusion injury in patients with fatty liver   and the clinical
      impact of steatotic liver on hepatic surgery.
AB  - Hepatic steatosis is one of the most common hepatic disorders in developed
      countries. The epidemic of obesity in developed countries has increased with its
      attendant complications, including metabolic syndrome and non-alcoholic fatty
      liver disease. Steatotic livers are particularly vulnerable to
      ischemia/reperfusion injury, resulting in an increased risk of postoperative
      morbidity and mortality after liver surgery, including liver transplantation.
      There is growing understanding of the molecular and cellular mechanisms and
      therapeutic approaches for treating ischemia/reperfusion injury in patients with
      steatotic livers. This review discusses the mechanisms underlying the
      susceptibility of steatotic livers to ischemia/reperfusion injuries, such as
      mitochondrial dysfunction and signal transduction alterations, and summarizes the
      clinical impact of steatotic livers in the setting of hepatic resection and liver
      transplantation. This review also describes potential therapeutic approaches,
      such as ischemic and pharmacological preconditioning, to prevent
      ischemia/reperfusion injury in patients with steatotic livers. Other approaches,
      including machine perfusion, are also under clinical investigation; however, many
      pharmacological approaches developed through basic research are not yet suitable
      for clinical application.

PMID- 24078002
TI  - Successful management of postoperative pain with pregabalin after thoracotomy.
AB  - PURPOSE: There is no established treatment for intercostal neuralgia associated
      with thoracotomy. We investigated the administration of pregabalin as a new
      perioperative treatment, assessing its safety and efficacy for intercostal
      neuralgia after thoracotomy. METHODS: Thirty patients suffering pain after
      thoracotomy severe enough to cause insomnia were prospectively enrolled and
      treated with 150 mg of pregabalin. We evaluated pain scores (Numeric Rating
      Scale, NRS), severity of nocturnal insomnia, and adverse effects before and after
      pregabalin administration. RESULTS: We noted significant decreases in pain
      scores, before vs. after pregabalin administration, from 8.2 +/- 1.3 to 3.4 +/-
      1.3 (p < 0.0001), with improvement in nocturnal insomnia in 29 out of 30
      patients. Eight patients reported adverse effects, including dizziness and
      daytime drowsiness; however, by reducing the dose of pregabalin, these effects
      were minimized while pain was controlled well. CONCLUSION: Pregabalin was highly
      effective for neuralgia associated with intercostal damage after thoracotomy.

PMID- 24078003
TI  - A recombinant trans-membrane protein hMnSOD-R9 inhibits the proliferation of
      cervical cancer cells in vitro.
AB  - Human manganese superoxide dismutase (hMnSOD) is a new type of cancer suppressor.
      Nonamer of arginine (R9) is an efficient protein transduction domain (PTD). The
      aim of the study was to improve the transduction efficiency of hMnSOD and
      investigate its activity in vitro. In this study, we designed, constructed,
      expressed, and purified a novel fusion protein containing the hMnSOD domain and
      R9 PTD (hMnSOD-R9). The DNA damaged by Fenton's reagent was found to be
      significantly reduced when treated with hMnSOD-R9. hMnSOD-R9 fusion protein was
      successfully delivered into HeLa cells. The MTT assay showed that proliferation
      of various cancer cell lines were inhibited by hMnSOD-R9 in a dose-dependent
      manner. In addition, the cell cycle of HeLa cells was arrested at the sub-G0
      phase by hMnSOD-R9. hMnSOD-R9 induced apoptosis of HeLa cells in a dose-dependent
      manner. With hMnSOD-R9 treatment, Bax, JNK, TBK1 gene expression was increased
      and STAT3 gene expression was gradually down-regulated in HeLa cells. We also
      found that apoptosis was induced by hMnSOD-R9 in HeLa cells via up-regulation of
      cleaved caspase-3 and down-regulation phospho-STAT3 pathway. These results
      indicated that hMnSOD-R9 may provide benefits to cervical cancer treatment.

PMID- 24078004
TI  - MiR-25 promotes gastric cancer cells growth and motility by targeting RECK.
AB  - Gastric cancer (GC) is the second leading cause of cancer-related death
      worldwide. Recently, accumulating evidence suggests that microRNAs (miRNAs) play
      prominent roles in tumorigenesis and metastasis. Here, we confirmed that miR-25
      was significantly increased in human GC tissues and cell lines. Forced expression
      of miR-25 remarkably enhanced cell proliferation, migration, and invasion in GC
      cells, whereas inhibition of miR-25 by inhibitor caused significant suppression
      of proliferation and significant increase of apoptosis. Moreover, inhibition of
      miR-25 significantly decreased migration and invasion of GC cells. Finally,
      reversion-inducing-cysteine-rich protein with kazal motifs (RECK) was found to be
      a target of miR-25. Overexpression of RECK could significantly reverse the
      oncogenic effect of miR-25. Taken together, miR-25 might promote GC cells growth
      and motility partially by targeting RECK.

PMID- 24078005
TI  - Fatal septicemia caused by the zoonotic bacterium Streptococcus iniae during an
      outbreak in Caribbean reef fish.
AB  - An outbreak of Streptococcus iniae occurred in the early months of 2008 among
      wild reef fish in the waters of the Federation of St Kitts and Nevis, lasting
      almost 2 months. Moribund and dead fish were collected for gross, histological,
      bacteriological, and molecular analysis. Necropsy findings included diffuse
      fibrinous pericarditis, pale friable livers, and serosal petechiation.
      Cytological and histological analysis revealed granulocytic and granulomatous
      inflammation with abundant coccoid bacterial organisms forming long chains.
      Necrosis, inflammation, and vasculitis were most severe in the pericardium,
      meninges, liver, kidneys, and gills. Bacterial isolates revealed beta-hemolytic,
      Gram-positive coccoid bacteria identified as S. iniae by amplification and 16S
      ribosomal RNA gene sequencing. Results from biochemical and antimicrobial
      susceptibility analysis, together with repetitive element palindromic polymerase
      chain reaction fingerprinting, suggest that a single strain was responsible for
      the outbreak. The inciting cause for this S. iniae-associated cluster of
      mortalities is unknown. 

PMID- 24078006
TI  - Rodent immunohistochemistry: pitfalls and troubleshooting.
AB  - Immunohistochemistry (IHC) is a common adjunct in pathology for morphologic
      diagnosis, research pathology, and studying the pathogenesis of the disease.
      Proper technique and interpretation of an immunohistochemistry assay is of utmost
      importance. A variety of problems, including the presence of artifacts
      (nonspecific background or other staining problems) and the differentiation
      between nonspecific and specific staining, commonly occur. It is essential that
      antibody quality and IHC technique be optimized. We review the histologic
      patterns of specific and nonspecific staining after using IHC techniques, as well
      as basic troubleshooting procedures, and provide some examples of nonspecific
      staining and other artifacts especially in formalin-fixed, paraffin-embedded
      tissues (FFPE) of mice. 

PMID- 24078007
TI  - Necrosuppurative orchitis and scrotal necrotizing dermatitis following
      intratesticular administration of zinc gluconate neutralized with arginine
      (EsterilSol) in 2 mixed-breed dogs.
AB  - Intratesticular injection of EsterilSol (zinc gluconate neutralized with
      arginine) is a chemical sterilant for male dogs sometimes used in population
      control campaigns. Adverse reactions have been reported in 1% to 4% of treated
      dogs, but detailed histomorphologic descriptions are lacking. During a behavioral
      study conducted in the Chilean Patagonia in 2012, severe necrosuppurative
      orchitis and ulcerative dermatitis were observed in 2 of 36 (6%) dogs sterilized
      with EsterilSol according to the manufacturer's instructions. Reactions were
      noted on days 8 and 7 postinjection and required scrotal ablation on days 8 and
      13, respectively; neither reaction was associated with the injection site.
      Although self-trauma following administration may have contributed, the cause of
      the adverse reactions is uncertain. EsterilSol is a relatively uncomplicated
      method to sterilize male dogs, but the occurrence of severe adverse reactions
      several days after administration emphasizes the need for the provision of long
      term monitoring and veterinary care during sterilization campaigns using this
      product. 

PMID- 24078008
TI  - The hazards of death by smoking in middle-aged women.
AB  - Recent studies have found that the risk of death continues to increase among
      female smokers, as compared with women who have never smoked. We wanted to
      examine the effect of smoking on all-cause and cause-specific mortality and
      calculate the corresponding population attributable fraction (PAF) of mortality
      in the Norwegian women and cancer study; a nationally representative prospective
      cohort study. We followed 85,320 women, aged 31-70 years, who completed a
      questionnaire in 1991-1997, through linkages to national registries through
      December 2008. Questionnaire data included information on lifestyle factors,
      including lifetime history of smoking. Poisson regression models were fitted to
      estimate relative risks (RRs) with 95 % confidence intervals (CIs) adjusting for
      age, birth cohort, education, postmenopausal status, alcohol consumption and body
      mass index, all at enrollment. During a mean follow-up time of 14 years 2,842
      deaths occurred. Compared with that of never smokers, current smokers had a
      mortality rate that was double (RR = 2.34; 95 % CI 2.13-2.62) from deaths
      overall, triple (RR = 3.30; 95 % CI 2.21-4.82) from cerebrovascular disease and
      myocardial infarction (RR = 3.65; 95 % CI 2.18-6.15), 12 times (RR = 12.16; 95 %
      CI 7.80-19.00) from lung cancer and seventeen times (RR = 17.00; 95 % CI 5.90
      48.78) from chronic obstructive pulmonary diseases. The PAF of mortality due to
      smoking was 34 % (CI 30-39). In summary, one in three deaths among middle aged
      women in Norway could have been prevented if the women did not smoke. More middle
      aged women, than ever before, are dying prematurely due to smoking in Norway.

PMID- 24078009
TI  - Chronic kidney disease is associated with high abdominal incisional hernia rates
      and wound healing disturbances.
AB  - BACKGROUND AND OBJECTIVES: Incisional hernias are among the most frequent
      complications following abdominal surgery with impact on morbidity and mortality
      rates. Elevated uremia toxins may inhibit granulation tissue formation and impair
      wound healing, thereby promoting incisional hernia development. Here, we
      quantified the hazard ratio for incisional hernia prevalence in patients at risk
      undergoing abdominal reoperations with interrelationship to kidney function. In
      the same cohort, incidence rates for de novo wound healing disturbances within a4
      month follow-up period were determined. DESIGN, SETTING, PARTICIPANTS AND
      MEASUREMENTS: Upon hospitalization for elective abdominal surgery in a university
      hospital (tertiary medical center), past medical histories were recorded in 251
      patients and incisional hernia prevalence rates were calculated. Known modifiers
      for hernia formation as well as laboratory values for estimated glomerular
      filtration rate (eGFR) were recorded. The status of wound healing was assessed by
      a blinded investigator 4 months postoperatively. Chronic kidney disease(CKD) was
      defined as eGFR <60 ml/min/1.73 m2. To identify independent risk factors for
      incisional hernia or postoperative wound healing disorder, multivariate
      regression analyses were performed. RESULTS: The incisional hernia prevalence was
      24.3 % in the overall cohort. Patients with CKD (32/251; 12.8 %)were more likely
      to suffer from incisional hernias with an odds ratio (OR) of 2.8 ([95 % CI 1.2
      6.1]; p = 0.014) than patients with eGFR >60 ml/min (219/251; 88.2 %). In
      multivariate analyses, CKD proved to be an independent risk factor for incisional
      hernia development with an OR similar to obesity (BMI>25; OR 2.6 [95 % CI 1.3
      5.1];p = 0.007). In the prospective analysis, disturbed wound healing occurred in
      32 of 251 (12.8 %) patients undergoing abdominal operations. Frequency of wound
      healing was increased when CKD was present (8/32; 25 %; OR 2.3[95 % CI 1.1-6.7];
      p = 0.026) compared to patients with eGFR>60 ml/min (24/219; 11 %). CONCLUSIONS:
      Chronic kidney disease is associated with impaired wound healing and constitutes
      an independent risk factor for incisional hernia development.

PMID- 24078010
TI  - Risk factors for predicting venous thromboembolism in patients with nephrotic
      syndrome: focus on haemostasis-related parameters.
AB  - PURPOSE: The venous thromboembolic events (VTE) incidence is high in nephrotic
      syndrome (NS). We aimed to assess prospectively the risk of VTE in a large cohort
      of NS patients and to identify predictive factors for VTE, especially haemostasis
      related parameters. METHODS: This is the prospective, observational study
      conducted in 256 adults with idiopathic NS. VTE were the study outcome. Clinical
      data, proteinuria, albuminuria, haemostasis and fibrinolysis parameters, and D
      dimers were evaluated every 6 months. RESULTS: Median follow-up time was 24 [IQR
      12-72] months. VTE cumulative and rate incidence were 11 % and 4.4 per 100
      patient-years. Baseline higher proteinuria,lower serum albumin, low antithrombin
      III activity, and,surprisingly, high ionized calcium were VTE independent
      predictors. Proteinuria and serum albumin cut-offs, and positive and negative
      predictive values (PPV and NPV) for VTE were 9.0 g/24 h (30 % PPV and 90 % NPV)
      and 1.5 g/dL (69 % PPV and 93 % NPV). CONCLUSIONS: The rate of VTE incidence of
      4.4 per 100 patient-years found in this prospective study confirms the idiopathic
      nephrotic syndrome as a thromboembolism-generating condition. Severe and
      unremitting proteinuria and hypoalbuminemia,low antithrombin III activity, and,
      surprisingly, high ionized calcium are independent VTE predictors.

PMID- 24078011
TI  - Copy number variation of chromosome 5A and its association with Q gene
      expression, morphological aberrations, and agronomic performance of winter wheat
      cultivars.
AB  - KEY MESSAGE: Our investigations combine chromosome 5A copy number variation
      associated with relative 5A Q gene expression and morphological and agronomic
      data to characterize the occurrence of speltoid plants in winter wheat cultivars.
      The occurrence of speltoid aberrants in wheat breeding is a serious problem that
      may result in rejection of a candidate cultivar during licensing. The spear
      shaped, hard threshing spike is caused by copy number reduction of the
      domestication gene Q, located on the long arm of wheat chromosome 5A. As a member
      of the APETALA2-like transcription factor family, the 5AQ gene is involved in
      flower development and pleiotropically controls other agronomic traits. In this
      report, a characterization of instability of chromosome 5A is given and effects
      due to the loss of the Q gene and other genes are discussed. Based on
      pyrosequencing, we correctly predicted the 5AQ copy number for 392 of 402 tested
      offspring plants (97.5 %) originating from single speltoid plants of eleven wheat
      cultivars. The findings indicate that the resulting speltoid plants were either
      reduced in chromosome 5A copy number or possessed a partial deletion of the
      distal end of chromosome arm 5AL. 5AQ specific real-time PCR analysis revealed
      varying transcription levels among cultivars. During early spike development, the
      relative transcription of the 5AQ gene was always lower in speltoids than in
      normal square headed wheat plants, most likely leading to the occurrence of the
      characteristic speltoid spike phenotype. The parallel analysis of 18 agronomic
      traits revealed pleiotropic effects governed by genes located on 5A. Our results
      demonstrate that through pyrosequencing one can identify aneuploidy or deletions
      within chromosome 5A to select against the occurrence of speltoid plants in wheat
      seedlings.

PMID- 24078012
TI  - Quantitative trait loci associated with tipburn, heat stress-induced
      physiological disorders, and maturity traits in crisphead lettuce.
AB  - Crisphead lettuce (Lactuca sativa L.) crops exhibit several economically
      important, physiological disorders when grown in high temperature conditions.
      These include tipburn, rib discoloration, premature bolting, ribbiness, and
      internal rib cracking. We evaluated seven physiological disorders and three
      agronomic traits segregating in a recombinant inbred line (RIL) population
      consisting of 152 F7 RILs derived from an intra-specific cross between two
      crisphead cultivars, L. sativa cv. Emperor x L. sativa cv. El Dorado; evaluations
      were carried out at each of two parental maturities in one planting and at one
      intermediate maturity in a second planting in each of 2 years for a total of six
      evaluations. A genetic map was developed using 449 polymorphic SNP markers; it
      comprises 807 cM in 20 linkage groups that covered 51 % of the nine lettuce
      chromosomes. Composite interval mapping revealed a total of 36 significant QTLs
      for eight out of the ten traits evaluated. Significant QTLs were distributed in
      11 linkage groups on seven of the chromosomes and accounted for up to 83 % of the
      phenotypic variation observed. The three largest QTLs for rib discoloration,
      which accounted individually for 7-21 % of the variation, were clustered with
      stem length, two with ribbiness and one with head firmness. Three major clusters
      of QTLs revealed pleiotropic effects or tight linkage between tipburn incidence
      and severity, head type, stem length, head firmness and ribbiness. One QTL,
      qTPB5.2, was detected in multiple trials and described 38-70 % of the variation
      in tipburn incidence. qTPB5.2 is, therefore, a useful candidate gene for breeding
      for tipburn resistance using marker-assisted selection.

PMID- 24078013
TI  - Time-resolved assessment of collateral flow using 4D CT angiography in large
      vessel occlusion stroke.
AB  - OBJECTIVES: In acute stroke patients with large vessel occlusion, collateral
      blood flow affects tissue fate and patient outcome. The visibility of collaterals
      on computed tomography angiography (CTA) strongly depends on the acquisition
      phase, but the optimal time point for collateral imaging is unknown. METHODS: We
      analysed collaterals in a time-resolved fashion using four-dimensional (4D) CTA
      in 82 endovascularly treated stroke patients, aiming to determine which
      acquisition phase best depicts collaterals and predicts outcome. Early, peak and
      late phases as well as temporally fused maximum intensity projections (tMIP) were
      graded using a semiquantitative regional leptomeningeal collateral score,
      compared with conventional single-phase CTA and correlated with functional
      outcome. RESULTS: The total extent of collateral flow was best visualised on
      tMIP. Collateral scores were significantly lower on early and peak phase as well
      as on single-phase CTA. Collateral grade was associated with favourable
      functional outcome and the strength of this relationship increased from earlier
      to later phases, with collaterals on tMIP showing the strongest correlation with
      outcome. CONCLUSIONS: Temporally fused tMIP images provide the best depiction of
      collateral flow. Our findings suggest that the total extent of collateral flow,
      rather than the velocity of collateral filling, best predicts clinical outcome.
      KEY POINTS: * Collateral flow visibility on CTA strongly depends on the
      acquisition phase * tMIP offers the best visualisation of the extent of
      collaterals * Outcome prediction may be better with tMIP than with earlier
      phases.* Total extent of collaterals seems more important than their filling
      speed * If triggered too early, CTA may underestimate collateral flow.

PMID- 24078015
TI  - Intracellular deoxyribonucleotide pool imbalance and DNA damage in cells treated
      with hydroxyurea, an inhibitor of ribonucleotide reductase.
AB  - Imbalance in the nucleotide pool of mammalian cells has been shown to result in
      genotoxic damage. The goal of this study was to devise a sensitive, reproducible
      and simple method for detection of nucleotide pool changes in mammalian cells
      that could be used for problem-solving activities in drug development, e.g.
      mechanistic explanation of a positive response in a mammalian in vitro
      genotoxicity test. The method evaluated in this study is based on ethanol
      extraction of the total nucleotide pool, heat treatment and filtration, treatment
      with calf intestine alkaline phosphatase to convert nucleotides to nucleosides
      and analysis of the nucleosides by high-performance liquid chromatography with
      ultraviolet detection. The method was applied to measure the intracellular levels
      of deoxyribonucleotides in mouse lymphoma (ML) L5178Y cells treated with various
      concentrations of a model compound, hydroxyurea (HU), a ribonucleotide reductase
      inhibitor. DNA strand breakage and micronuclei formation were assessed in the
      same experiments. Imbalance of nucleotide pool (i.e. changes in the relative
      ratios between individual nucleotide pools) in HU-treated ML cells has been
      observed already at a concentration of 0.01 mmol/l, whereas genotoxic effects
      became apparent only at higher concentrations of HU (i.e. 0.25 mmol/l and higher)
      as indicated by formation of DNA strand breaks and micronuclei. 

PMID- 24078014
TI  - The perception of pain and its management in disorders of consciousness.
AB  - One of the most controversial issues in the management of patients in a
      vegetative state or a minimally conscious state concerns their hypothetical
      capacity to continue to experience pain despite an apparent absence of self- and
      environmental awareness. Recent functional neuroimaging studies have shown a
      greater perception of pain in patients in minimally conscious state compared with
      patients in vegetative state, suggesting the possible involvement of preserved
      cognitive mechanisms in the process of pain modulation in the former. In
      addition, a subgroup of patients might continue to experience some elementary
      emotional and affective feelings, as suggested by the reported activation of
      specific cerebral areas in response to situations, which commonly generate
      empathy. However, the available evidence is not sufficient to draw conclusions
      about the presence or absence of pain experience in patients with disorders of
      consciousness. Future studies should contribute to a better understanding of
      which central neural pathways are involved in the perception and modulation of
      pain in healthy subjects and in patients with severe brain injuries. Such studies
      should thus also improve our know-how about pain management in this particularly
      challenging group of patients. 

PMID- 24078017
TI  - Desulfotomaculum tongense sp. nov., a moderately thermophilic sulfate-reducing
      bacterium isolated from a hydrothermal vent sediment collected from the Tofua Arc
      in the Tonga Trench.
AB  - A novel, strictly anaerobic, moderately thermophilic, endospore-forming, sulfate
      reducing bacterium, designated TGB60-1T, was isolated from a hydrothermal
      sediment vent collected from the Tofua Arc in the Tonga Trench. The strain was
      characterized phenotypically and phylogenetically. The isolated strain was
      observed to be Gram-positive, with slightly curved rod-shaped cells and a polar
      flagellum. Strain TGB60-1T was found to grow anaerobically at 37-60  degrees C
      (optimum, 50  degrees C), at pH 6.0-8.5 (optimum, pH 7.0) and with 1.0-4.0 %
      (w/v) NaCl (optimum, 3.0 %). The electron acceptors utilised were determined to
      be sulfate, sulfite, and thiosulfate. Strain TGB60-1T was found to utilise
      pyruvate and H2 as electron donors. Strain TGB60-1T was determined to be related
      to representatives of the genus Desulfotomaculum and the closest relatives within
      this genus were identified as Desulfotomaculum halophilum SEBR 3139T,
      Desulfotomaculum alkaliphilum S1T and Desulfotomaculum peckii LINDBHT1T (92.7,
      92.1, and 91.8 % 16S rRNA gene sequence similarity, respectively). The major
      fatty acids (>20 %) were identified as C16:0 and C18:1 omega7c. The G+C content
      of the genomic DNA of this novel bacterium was determined to be 53.9 mol%. Based
      on this polyphasic taxonomic study, strain TGB60-1T is considered to represent a
      novel species in the genus Desulfotomaculum, for which the name Desulfotomaculum
      tongense sp. nov. is proposed. The type strain of D. tongense is strain TGB60-1T
      (= KTCT 4534T = JCM 18733T).

PMID- 24078019
TI  - Weak reward source memory in depression reflects blunted activation of VTA/SN and
      parahippocampus.
AB  - Reward responses in the medial temporal lobes and dopaminergic midbrain boost
      episodic memory formation in healthy adults, and weak memory for emotionally
      positive material in depression suggests this mechanism may be dysfunctional in
      major depressive disorder (MDD). To test this hypothesis, we performed a study in
      which unmedicated adults with MDD and healthy controls encoded drawings paired
      with reward or zero tokens during functional magnetic resonance imaging. In a
      recognition test, participants judged whether drawings were previously associated
      with the reward token ('reward source') or the zero token ('zero source'). Unlike
      controls, depressed participants failed to show better memory for drawings from
      the reward source vs the zero source. Consistent with predictions, controls also
      showed a stronger encoding response to reward tokens vs zero tokens in the right
      parahippocampus and dopaminergic midbrain, whereas the MDD group showed the
      opposite pattern-stronger responses to zero vs reward tokens-in these regions.
      Differential activation of the dopaminergic midbrain by reward vs zero tokens was
      positively correlated with the reward source memory advantage in controls, but
      not depressed participants. These data suggest that weaker memory for positive
      material in depression reflects blunted encoding responses in the dopaminergic
      midbrain and medial temporal lobes.

PMID- 24078018
TI  - Underconnectivity of the superior temporal sulcus predicts emotion recognition
      deficits in autism.
AB  - Neurodevelopmental disconnections have been assumed to cause behavioral
      alterations in autism spectrum disorders (ASDs). Here, we combined measurements
      of intrinsic functional connectivity (iFC) from resting-state functional magnetic
      resonance imaging (fMRI) with task-based fMRI to explore whether altered activity
      and/or iFC of the right posterior superior temporal sulcus (pSTS) mediates
      deficits in emotion recognition in ASD. Fifteen adults with ASD and 15 matched
      controls underwent resting-state and task-based fMRI, during which participants
      discriminated emotional states from point light displays (PLDs). Intrinsic FC of
      the right pSTS was further examined using 584 (278 ASD/306 controls) resting
      state data of the Autism Brain Imaging Data Exchange (ABIDE). Participants with
      ASD were less accurate than controls in recognizing emotional states from PLDs.
      Analyses revealed pronounced ASD-related reductions both in task-based activity
      and resting-state iFC of the right pSTS with fronto-parietal areas typically
      encompassing the action observation network (AON). Notably, pSTS-hypo-activity
      was related to pSTS-hypo-connectivity, and both measures were predictive of
      emotion recognition performance with each measure explaining a unique part of the
      variance. Analyses with the large independent ABIDE dataset replicated reductions
      in pSTS-iFC to fronto-parietal regions. These findings provide novel evidence
      that pSTS hypo-activity and hypo-connectivity with the fronto-parietal AON are
      linked to the social deficits characteristic of ASD.

PMID- 24078022
TI  - Targeted mutagenesis tools for modelling psychiatric disorders.
AB  - In the 1980s, the basic principles of gene targeting were discovered and forged
      into sharp tools for efficient and precise engineering of the mouse genome. Since
      then, genetic mouse models have substantially contributed to our understanding of
      major neurobiological concepts and are of utmost importance for our comprehension
      of neuropsychiatric disorders. The "domestication" of site-specific recombinases
      and the continuous creative technological developments involving the
      implementation of previously identified biological principles such as
      transcriptional and posttranslational control now enable conditional mutagenesis
      with high spatial and temporal resolution. The initiation and successful
      accomplishment of large-scale efforts to annotate functionally the entire mouse
      genome and to build strategic resources for the research community have
      significantly accelerated the rapid proliferation and broad propagation of mouse
      genetic tools. Addressing neurobiological processes with the assistance of
      genetic mouse models is a routine procedure in psychiatric research and will be
      further extended in order to improve our understanding of disease mechanisms. In
      light of the highly complex nature of psychiatric disorders and the current lack
      of strong causal genetic variants, a major future challenge is to model of
      psychiatric disorders more appropriately. Humanized mice, and the recently
      developed toolbox of site-specific nucleases for more efficient and simplified
      tailoring of the genome, offer the perspective of significantly improved models.
      Ultimately, these tools will push the limits of gene targeting beyond the mouse
      to allow genome engineering in any model organism of interest. 

PMID- 24078021
TI  - Medial frontal cortex and anterior insula are less sensitive to outcome
      predictability when monetary stakes are higher.
AB  - Prior research links greater activation of posterior medial frontal cortex (pMFC)
      and anterior insula (AI) with decreasing outcome predictability during decision
      making, as measured by decreasing probability for the more likely outcome out of
      two or increasing outcome variance. In addition to predictability, much work
      indicates that the magnitude or 'stakes' of the outcome is also important.
      Despite the interest in the neural correlates of these decision variables, it is
      unknown whether pMFC and AI are differentially sensitive to predictability when
      magnitude is varied. This study examined brain activity during decision making in
      relation to decreasing outcome predictability for low as compared with high
      magnitude decisions. For low magnitude decisions, reduced predictability of the
      outcome was associated with greater activity in pMFC and bilateral AI,
      replicating prior studies. In contrast, there was no relationship between
      predictability and brain activity for high magnitude decisions, which tended to
      elicit greater pMFC and AI activity than low magnitude decisions for more
      predictable outcomes. These data indicate that the relationship between outcome
      predictability and pMFC and AI activity during decision making depends on
      magnitude, and suggest that these regions may be responding to the motivational
      salience of the decision rather than predictability information per se. 

PMID- 24078020
TI  - Psychological, endocrine and neural responses to social evaluation in subclinical
      depression.
AB  - This study aimed to identify vulnerability patterns in psychological,
      physiological and neural responses to mild psychosocial challenge in a population
      that is at a direct risk of developing depression, but who has not as yet
      succumbed to the full clinical syndrome. A group of healthy and a group of
      subclinically depressed participants underwent a modified Montreal Imaging Stress
      task (MIST), a mild neuroimaging psychosocial task and completed state self
      esteem and mood measures. Cortisol levels were assessed throughout the session.
      All participants showed a decrease in performance self-esteem levels following
      the MIST. Yet, the decline in performance self-esteem levels was associated with
      increased levels of anxiety and confusion in the healthy group, but increased
      levels of depression in the subclinical group, following the MIST. The
      subclinical group showed overall lower cortisol levels compared with the healthy
      group. The degree of change in activity in the subgenual anterior cingulate
      cortex in response to negative evaluation was associated with increased levels of
      depression in the whole sample. Findings suggest that even in response to a mild
      psychosocial challenge, those individuals vulnerable to depression already show
      important maladaptive response patterns at psychological and neural levels. The
      findings point to important targets for future interventions. 

PMID- 24078023
TI  - Trends in hospitalizations of patients with sepsis and factors associated with
      inpatient mortality in the Region of Madrid, 2003-2011.
AB  - The objectives of this investigation were to study the temporal trends in
      hospitalizations of patients with sepsis in the Region of Madrid (Spain) from
      2003 to 2011 and analyze the factors associated with inpatient mortality. All
      sepsis hospitalizations from the minimum basic data set (MBDS) during 2003 to
      2011 in the Region of Madrid were analyzed. Genderspecific crude and age-adjusted
      rates were calculated each year. Factors associated with death in these patients
      were studied with bivariate and multivariate analyses. Simultaneously, sepsis
      inpatients also underwent descriptive analysis. The study included 98,898 sepsis
      episodes. The incidence of sepsis hospitalizations per 100,000 habitants
      increased in males from 114.4 in 2003 to 262.2 in 2011, and in females from 91.2
      to 209.1 between 2003 and 2011. The observed inpatient mortality was 23.2 %.
      There were 45,936 (46.4 %) episodes of severe sepsis (>=1 organ failure),
      revealing a clear upward trend, especially in multi-organ failure. Severe sepsis
      mortality showed a decreasing trend in both males (40.0 to 31.8 % from 2003
      through 2011) and females (41.6 to 35.2 % from 2003 through 2011). Death was most
      frequent among the elderly and in patients with more organ failures and
      comorbidities. In a populous region of Southern Europe, an upward trend in sepsis
      incidence was observed between 2003 and 2011, as well as a decreasing trend in
      mortality for sepsis inpatients. Mortality increased with age, comorbidities, and
      organ failures.

PMID- 24078025
TI  - Safety of hematopoietic stem cell transplantation from hepatitis B core
      antibodies-positive donors with low/undetectable viremia in HBV-naive children.
AB  - Scarce data exist on allogeneic hematopoietic stem cell transplantation (HSCT)
      outcomes in hepatitis B virus (HBV)-naive recipients from HBV-experienced donors.
      Long-term follow-up is herein reported for 17 allogeneic HSCT performed in 13 HBV
      naive children from HBc-antibodies-positive donors between 2006 and 2012. Four
      donors were HBs-antigen-positive, with detectable but low viremia in 2 cases (<2
      log10IU/ml). HBV-DNA was undetectable in all transplanted cell products.
      Recipients' HBV prophylaxis consisted of pre-transplant vaccination, polyvalent
      immune globulins, specific anti-HBV immune globulins, and/or oral lamivudine in
      3, 12, 8, and 8 children, respectively. No case of HBV transmission occurred
      based on negative close monitoring of recipients' HBV serology and plasma HBV-DNA
      during a median follow-up of 22 months. In case of undetectable viremia in the
      donor, prophylaxis with vaccination and/or immune globulins in the recipient
      seems to be sufficient and lamivudine prophylaxis might be unnecessary to prevent
      viral transmission. In case of undetectable viremia in the donor, a systematic
      screening of HBV DNA in the stem cell product might be unnecessary to confirm the
      low risk of viral transmission. Prior exposure to HBV in the donor should not be
      considered a contraindication to HSCT.

PMID- 24078024
TI  - Subtype determination of Blastocystis isolates by matrix-assisted laser
      desorption/ionisation time-of-flight mass spectrometry (MALDI-TOF MS).
AB  - The pathogenic role of the enteric parasite Blastocystis remains controversial.
      Recent studies have suggested that various subtypes (STs) found in human samples
      could be correlated to the presence or absence and variability of clinical
      manifestations, and that STs can differ with respect to drug sensitivity.
      Polymerase chain reaction (PCR) techniques used to determine these STs are
      expensive and are usually restricted to research laboratory settings. This study
      evaluates the potential application of the inexpensive matrix-assisted laser
      desorption/ionisation time-of-flight mass spectrometry (MALDI-TOF MS) technique
      to discriminate Blastocystis STs. A database of parasitic protein signatures was
      constructed for five Blastocystis STs, and the reference spectra were challenged
      with those from 19 axenic cultures of ST1, ST2, ST3, ST4 and ST8 and those from
      nine xenic liquid cultures of ST3 and ST4. Samples from axenic cultures were
      prepared using standard formic acid extraction and direct deposition procedures.
      The reference spectra revealed five distinct spectral profiles, and the database
      library allowed for discrimination between all of the cultures with reliability
      indices ranging from 2.038 to greater than 2.8 when an extraction was performed.
      The direct deposition procedure resulted in greater variability in the
      discrimination and direct MALDI-TOF MS identification from xenic liquid cultures
      was effective in 3 out of 9 samples. MALDI-TOF MS proved to be an effective
      technology for efficiently discriminating Blastocystis STs in axenic cultures.

PMID- 24078026
TI  - Bayesian estimation of HIV-1 dynamics in vivo.
AB  - Statistical analysis of viral dynamics in HIV-1 infected patients undergoing
      structured treatment interruptions were performed using a novel model that
      accounts for treatment efficiency as well as total CD8+ T cell counts. A brief
      review of parameter estimates obtained in other studies is given, pointing to a
      considerable variation in the estimated values. A Bayesian approach to parameter
      estimation was used with longitudinal measurements of CD4+ and CD8+ T cell counts
      and HIV RNA. We describe an estimation procedure which uses spline approximations
      of CD8+ T cells dynamics. This approach reduces the number of parameters that
      must be estimated and is especially helpful when the CD8+ T cells growth function
      has a delayed dependence on the past. Seven important parameters related to HIV-1
      in-host dynamics were estimated, most of them treated as global parameters across
      the group of patients. The estimated values were mainly in keeping with the
      estimates obtained in other reports, but our paper also introduces the estimates
      of some new parameters which supplement the current knowledge. The method was
      also tested on a simulated data set. 

PMID- 24078028
TI  - Intradermal absorbable sutures to close pilonidal sinus wounds:  a safe closure
      method?
AB  - PURPOSE: The aim of this study was to demonstrate the safety of using intradermal
      absorbable sutures for pilonidal sinus skin closure. METHODS: The study was
      prospectively carried out in 203 patients randomized into two groups of patients.
      In the first group (103 patients), interrupted sutures were used; in the second
      group (100 patients), a continuous intradermal suture was used. We have analyzed
      the time off work, time to walk without pain, time to sit on the toilet without
      pain, wound infections, satisfaction rate and esthetic results. RESULTS: There
      were no significant differences between the groups with regard to the time off
      work, time to walk without pain and time to sit on a toilet without pain. There
      was also no significant difference between the groups with regard to the wound
      infection rates (p = 0.64). The study suggested that the patients' satisfaction
      was higher when an intradermal suture was used (p = 0.001). Similarly, a better
      cosmetic appearance of the scar was obtained with an intradermal suture (p =
      0.01). CONCLUSIONS: Our results suggest that using intradermal sutures after
      excision and primary closure of the pilonidal sinus is safe and has advantages in
      terms of the cosmetic results and patient satisfaction.

PMID- 24078029
TI  - Simultaneous disruption of estrogen receptor and Wnt/beta-catenin signaling is
      involved in methyl amooranin-mediated chemoprevention of mammary gland
      carcinogenesis in rats.
AB  - Methyl-amoorain (methyl-25-hydroxy-3-oxoo-lean-12-en-28-oate, AMR-Me), a novel
      synthetic oleanane triterpenoid, exerts a striking chemopreventive effect against
      7,12-dimethylbenz(a)anthracene (DMBA)-induced rat mammary tumorigenesis through
      antiproliferative and proapoptotic actions. Nevertheless, the underlying
      mechanisms of action remain to be established. As estrogen receptor (ER) and
      canonical Wnt/b-catenin signaling are involved in the development and progression
      of breast cancer, the current study was designed to investigate the effects of
      AMR-Me treatment on the expressions of ER-a, ER-b, b-catenin and cyclin D1 in rat
      mammary tumors induced by DMBA. Mammary tumor samples were harvested from an 18
      week chemopreventive study in which AMR-Me (0.8-1.6 mg/kg) was shown to inhibit
      mammary carcinogenesis in a dose-response manner. The expressions of ER-a, ER-b,
      b-catenin, and cyclin D1 were determined by immunohistochemistry and reverse
      transcription-polymerase chain reaction. AMR-Me downregulated the expression of
      intratumor ER-a and ER-b and lowered the ratio of ER-a to ER-b. AMR-Me also
      reduced the expression, cytoplasmic accumulation, and nuclear translocation of b
      catenin, the essential transcriptional cofactor for Wnt signaling. Furthermore,
      AMR-Me modulated the expression of cell growth regulatory gene cyclin D1, which
      is a downstream target for both ER and Wnt signaling. AMR-Me at 1.6 mg/kg for 18
      weeks did not exhibit any hepatotoxicity or renotoxicity. The results of the
      present study coupled with our previous findings indicate that simultaneous
      disruption of ER and Wnt/b-catenin signaling possibly contributes to
      antiproliferative and apoptosis-inducing effects implicated in AMR-Me-mediated
      chemoprevention of DMBA-induced breast tumorigenesis in rats. Our results also
      suggest a possible crosstalk between two key regulatory pathways, namely ER and
      Wnt/b-catenin signaling, involved in mammary carcinogenesis and the value of
      simultaneously targeting these pathways to achieve breast cancer chemoprevention.

PMID- 24078030
TI  - Characterization of a unique motif in LIM mineralization protein-1 that interacts
      with jun activation-domain-binding protein 1.
AB  - Development and repair of the skeletal system and other organs are highly
      dependent on precise regulation of the bone morphogenetic protein (BMP) pathway.
      The use of BMPs clinically to induce bone formation has been limited in part by
      the requirement of much higher doses of recombinant proteins in primates than
      were needed in cell culture or rodents. Therefore, increasing cellular
      responsiveness to BMPs has become our focus. We determined that an osteogenic LIM
      mineralization protein, LMP-1 interacts with Smurf1 (Smad ubiquitin regulatory
      factor 1) and prevents ubiquitination of Smads resulting in potentiation of BMP
      activity. In the region of LMP-1 responsible for bone formation, there is a motif
      that directly interacts with the Smurf1 WW2 domain and thus effectively competes
      for binding with Smad1 and Smad5, key signaling proteins in the BMP pathway. Here
      we show that the same region also contains a motif that interacts with Jun
      activation-domain-binding protein 1 (Jab1) which targets a common Smad, Smad4,
      shared by both the BMP and transforming growth factor-beta (TGF-beta) pathways,
      for proteasomal degradation. Jab1 was first identified as a coactivator of the
      transcription factor c-Jun. Jab1 binds to Smad4, Smad5, and Smad7, key
      intracellular signaling molecules of the TGF-beta superfamily, and causes
      ubiquitination and/or degradation of these Smads. We confirmed a direct
      interaction of Jab1 with LMP-1 using recombinantly expressed wild-type and mutant
      proteins in slot-blot-binding assays. We hypothesized that LMP-1 binding to Jab1
      prevents the binding and subsequent degradation of these Smads causing increased
      accumulation of osteogenic Smads in cells. We identified a sequence motif in LMP
      1 that was predicted to interact with Jab1 based on the MAME/MAST sequence
      analysis of several cellular signaling molecules that are known to interact with
      Jab-1. We further mutated the potential key interacting residues in LMP-1 and
      showed loss of binding to Jab1 in binding assays in vitro. The activities of
      various wild-type and mutant LMP-1 proteins were evaluated using a BMP-responsive
      luciferase reporter and alkaline phosphatase assay in mouse myoblastic cells that
      were differentiated toward the osteoblastic phenotype. Finally, to strengthen
      physiological relevance of LMP-1 and Jab1 interaction, we showed that
      overexpression of LMP-1 caused nuclear accumulation of Smad4 upon BMP treatment
      which is reflective of increased Smad signaling in cells.

PMID- 24078031
TI  - Ameliorating effect of eugenol on hyperglycemia by attenuating the key enzymes of
      glucose metabolism in streptozotocin-induced diabetic rats.
AB  - Epidemiological studies have demonstrated that diabetes mellitus is a serious
      health burden for both governments and healthcare providers. This study was
      hypothesized to evaluate the antihyperglycemic potential of eugenol by determine
      the activities of key enzymes of glucose metabolism in streptozotocin (STZ)
      induced diabetic rats. Diabetes was induced into male albino Wistar rats by
      intraperitoneal administration of STZ (40 mg/kg body weight (b.w.)). Eugenol was
      administered to diabetic rats intragastrically at 2.5, 5, and 10 mg/kg b.w. for
      30 days. The dose 10 mg/kg b.w. significantly reduced the levels of blood glucose
      and glycosylated hemoglobin (HbA1c) and increased plasma insulin level. The
      altered activities of the key enzymes of carbohydrate metabolism such as
      hexokinase, pyruvate kinase, glucose-6-phosphate dehydrogenase, glucose-6
      phosphatase, fructose-1,6-bisphosphatase, and liver marker enzymes (AST, ALT, and
      ALP), creatine kinase and blood urea nitrogen in serum and blood of diabetic rats
      were significantly reverted to near normal levels by the administration of
      eugenol. Further, eugenol administration to diabetic rats improved body weight
      and hepatic glycogen content demonstrated the antihyperglycemic potential of
      eugenol in diabetic rats. The present findings suggest that eugenol can
      potentially ameliorate key enzymes of glucose metabolism in experimental
      diabetes, and it is sensible to broaden the scale of use of eugenol in a trial to
      alleviate the adverse effects of diabetes.

PMID- 24078041
TI  - Specific labeling and assignment strategies of valine methyl groups for NMR
      studies of high molecular weight proteins.
AB  - The specific protonation of valine and leucine methyl groups in proteins is
      typically achieved by overexpressing proteins in M9/D2O medium supplemented with
      either labeled alpha-ketoisovalerate for the labeling of the four prochiral
      methyl groups or with 2-acetolactate for the stereospecific labeling of the
      valine and leucine side chains. However, when these labeling schemes are applied
      to large protein assemblies, significant overlap between the correlations of the
      valine and leucine methyl groups occurs, hampering the analysis of 2D methyl
      TROSY spectra. Analysis of the leucine and valine biosynthesis pathways revealed
      that the incorporation of labeled precursors in the leucine pathway can be
      inhibited by the addition of exogenous l-leucine-d10. We exploited this property
      to label stereospecifically the pro-R and pro-S methyl groups of valine with
      minimal scrambling to the leucine residues. This new labeling protocol was
      applied to the 468 kDa homododecameric peptidase TET2 to decrease the complexity
      of its NMR spectra. All of the pro-S valine methyl resonances of TET2 were
      assigned by combining mutagenesis with this innovative labeling approach. The
      assignments were transferred to the pro-R groups using an optimally labeled
      sample and a set of triple resonance experiments. This improved labeling scheme
      enables us to overcome the main limitation of overcrowding in the NMR spectra of
      prochiral methyl groups, which is a prerequisite for the site-specific
      measurement of the structural and dynamic parameters or for the study of
      interactions in very large protein assemblies.

PMID- 24078042
TI  - Independent valine and leucine isotope labeling in Escherichia coli protein
      overexpression systems.
AB  - The addition of labeled alpha-ketoisovalerate to the growth medium of a protein
      expressing host organism has evolved into a versatile tool to achieve concomitant
      incorporation of specific isotopes into valine- and leucine- residues. The
      resulting target proteins represent excellent probes for protein NMR analysis.
      However, as the sidechain resonances of these residues emerge in a narrow
      spectral range, signal overlap represents a severe limitation in the case of high
      molecular-weight NMR probes. We present a protocol to eliminate leucine labeling
      by supplying the medium with unlabeled alpha-ketoisocaproate. The resulting
      spectra of a model protein exclusively feature valine signals of increased
      intensity, confirming the method to be a first example of independent valine and
      leucine labeling employing alpha-ketoacid precursor compounds.

PMID- 24078043
TI  - Neural correlates of the mini-SEA (Social cognition and Emotional Assessment) in
      behavioral variant frontotemporal dementia.
AB  - Although Frontotemporal Dementia (FTD) is the second most common form of dementia
      after Alzheimer's disease, its diagnosis remains particularly challenging today.
      This is particularly true for the behavioral variant (bvFTD), the most common
      phenotype of FTD, which is characterised by dramatic changes in personal and
      social conduct. Novel clinical cognitive tests have been recently proposed to
      diagnose and assess these patients. Among them, the mini-SEA (Social cognition &
      Emotional Assessment) has shown promising results. This quick clinical tool
      evaluates emotion recognition and theory of mind deficits, both recognized as
      hallmark features of bvFTD. In this study, we investigated the neural correlates
      of the mini-SEA in twenty bvFTD patients, using single photon emission computed
      tomography (SPECT) and focusing on the mPFC. Results showed that detection of
      faux pas during a theory of mind evaluation was related to rostral mPFC perfusion
      (BA 10) while recognition of emotion involved more dorsal regions within the mPFC
      (BA 9). As significant and early dysfunction of the mPFC has been extensively
      described in bvFTD, this study supports the use of the mini-SEA in evaluation and
      diagnosis purposes in bvFTD.

PMID- 24078044
TI  - Molecular evolution of the hemagglutinin and neuraminidase genes of pandemic
      (H1N1) 2009 influenza viruses in Sendai, Japan, during 2009-2011.
AB  - Analyzing the evolutionary pattern of the influenza A(H1N1)pdm09 strain in
      different regions is important for understanding its diversification. We
      therefore conducted this study to elucidate the genetic variability and molecular
      evolution of the influenza A(H1N1)pdm09 strains that circulated during the 2009
      2010 and 2010-2011 influenza seasons in Sendai, Japan. Nasopharyngeal swab
      specimens were collected from patients with influenza-like illnesses who visited
      outpatient clinics in Sendai City, Japan, from September 2009 to April 2011. A
      total of 75 isolates were selected from September 2009 to April 2011 to analyze
      the genetic changes in the entire hemagglutinin 1 (HA1) segment of the HA gene
      and the neuraminidase (NA) gene based on sequence analysis. Bayesian coalescent
      Markov chain Monte Carlo analyses of HA1 and NA gene sequences were performed for
      further analysis. High sequence identities were observed for HA1 and NA in
      influenza A(H1N1)pdm09, displaying 99.06 and 99.33 % nucleotide identities,
      respectively, with the A(H1N1)pdm09 vaccine strain A/California/07/2009. The
      substitution rates of nucleotides for HA1 in the 2009-2010 and 2010-2011 were 1.5
      * 10-3 and 1.6 * 10-3 substitutions per site per year, respectively. Phylogenetic
      tree analysis demonstrated that Sendai isolates were clustered into global clade
      7, which is characterized by an S203T mutation in the HA1 gene. Moreover, two
      distinct circulation clusters were present in the 2010-2011 season. Mutations
      were present in antigenic or receptor-binding domains of the HA1 segment,
      including A141V, S143G, S183P, S185T, and S203T. The Bayesian skyline plot model
      illustrated a steady rate for the maintenance of genetic diversity, followed by a
      slight increase in the later part of the 2010-2011 season. Selection analysis
      revealed that the HA1 (position 197) and NA (position 46) sites were under
      positive selection; however, no known mutation conferring resistance to NA
      inhibitors such as H275Y was observed. The effect on control of the influenza
      A(H1N1)pdm09 virus, including vaccine strain selection, requires continuous
      monitoring of the strain by genetic surveillance.

PMID- 24078046
TI  - Results of the PERFORM magnetic resonance imaging study.
AB  - The PERFORM MRI Project was an ancillary study of the PERFORM trial. Its aim was
      to investigate the potential effects of terutroban in patients with
      atherothrombotic disorders, in comparison to aspirin, on the evolution of
      magnetic resonance imaging (MRI) lesions after a recent ischemic stroke or
      transient ischemic attack (TIA). The change in both hypointense and hyperintense
      lesions on the fluid attenuated inversion recovery (FLAIR) sequence, in the total
      brain volume and in the hippocampal volume from baseline (M1) to the final visit
      (M24) was assessed as well as the number of emergent microbleeds. A total of 748
      patients had their MRI examination validated both at M1 and M24 during the study.
      At baseline, the volume of hypointense and hyperintense lesions on FLAIR images,
      the total brain volume, the hippocampal volume and the number of patients with
      microbleeds did not differ between the two groups. During follow-up, the mean
      volumetric increase of lesions hypointense or hyperintense on FLAIR images (from
      5 to 8 %), the mean reduction of total brain volume (-0.4 %) and of hippocampal
      volume (-4 %), did not differ between the two treatment arms. The same parameters
      analysed ipsilateral to the ischaemic lesion did not differ either between the
      two groups. In the terutroban group, 16.3 % of patients presented with emergent
      microbleeds, 10.7 % in the aspirin group; this difference was not significant. In
      the PERFORM study, the progression of FLAIR lesions, of cerebral or hippocampal
      atrophy and of microbleeds did not differ between patients treated by terutroban
      and those treated by aspirin.

PMID- 24078047
TI  - Phelan-McDermid syndrome presenting with autistic spectrum: are we
      underdiagnosing chromosomal diseases in patients with autism?

PMID- 24078045
TI  - Expression of a non-coding RNA in ectromelia virus is required for normal plaque
      formation.
AB  - Poxviruses are dsDNA viruses with large genomes. Many genes in the genome remain
      uncharacterized, and recent studies have demonstrated that the poxvirus
      transcriptome includes numerous so-called anomalous transcripts not associated
      with open reading frames. Here, we characterize the expression and role of an
      apparently non-coding RNA in orthopoxviruses, which we call viral hairpin RNA
      (vhRNA). Using a bioinformatics approach, we predicted expression of a transcript
      not associated with an open reading frame that is likely to form a stem-loop
      structure due to the presence of a 21 nt palindromic sequence. Expression of the
      transcript as early as 2 h post-infection was confirmed by northern blot and
      analysis of publicly available vaccinia virus infected cell transcriptomes. The
      transcription start site was determined by RACE PCE and transcriptome analysis,
      and early and late promoter sequences were identified. Finally, to test the
      function of the transcript we generated an ectromelia virus knockout, which
      failed to form plaques in cell culture. The important role of the transcript in
      viral replication was further demonstrated using siRNA. Although the function of
      the transcript remains unknown, our work contributes to evidence of an
      increasingly complex poxvirus transcriptome, suggesting that transcripts such as
      vhRNA not associated with an annotated open reading frame can play an important
      role in viral replication.

PMID- 24078048
TI  - Magnetic resonance imaging following endoscopic nasopharyngectomy with a
      potassium-titanyl-phosphate (KTP) laser for early locally recurrent
      nasopharyngeal carcinoma.
AB  - INTRODUCTION: This study aims to investigate the spectrum of magnetic resonance
      imaging (MRI) features following endoscopic potassium-titanyl-phosphate (KTP)
      laser nasopharyngectomy. METHODS: From January 2005 to December 2010, a total of
      35 patients underwent KTP laser nasopharyngectomy for early recurrent NPC (rT1 or
      rT2) at our institute. Those who were lost to follow-up (N = 2) were excluded.
      Among the remaining patients, ten were proved to have locally recurrent disease
      and the other 23 not locally recurrent within 2 years of postoperative follow-up.
      Their serial MRIs were evaluated. RESULTS: Postoperative nasopharyngeal mucosal
      changes were present in all of the subjects on first follow-up MRI, ranged from
      focal mucosal thinning (19/33, 57.6 %), focal mucosal thickening (8/33, 24.2 %)
      to mixed thinning and thickening (6/33, 18.2 %). Nasopharyngeal submucosal soft
      tissue volume loss was found in 23 (23/33, 69.7 %), and parapharyngeal soft
      tissue necrosis was found in 3 (3/33, 9.1 %). Postoperative bone marrow change
      involved the clivus in 31 (31/33, 93.9 %) and the petrous or pterygoid in 17
      (17/33, 51.5 %). There were no significant differences between the two groups in
      the changes of mucosa, adjacent soft tissue, and skull base on the first MRI. The
      evaluation of serial MRIs disclosed that the patients in the recurrent group were
      more likely to develop new or enlarging mucosal masses (p = 0.01) and enlarging
      skull base changes (p = 0.0001). CONCLUSIONS: KTP laser nasopharyngectomy induces
      mucosal and skull base changes that could be misinterpreted as tumor progression
      on early postoperative MRI scans. Sequential imaging is required to distinguish
      between postoperative changes and progressive disease.

PMID- 24078050
TI  - Assessment of organic and inorganic contaminants in sediments of an urban
      tropical eutrophic reservoir.
AB  - Although the Ibirite reservoir (an urban tropical eutrophic reservoir) has been
      the recipient of the discharge of a large volume of raw urban sewage, the key
      cause of ecosystem degradation has been historically solely attributed to the
      discharge of effluents from an oil refinery. This fact motivated an investigation
      to unravel the compositions of contaminants in the sediments to evaluate their
      distributions, possible sources, and potential impacts on sediment-water quality.
      The concentrations of polycyclic aromatic and aliphatic hydrocarbons and of
      metals and metalloids were, in general, significantly lower than some selected
      polluted sites used for comparison. Calculated distribution indexes showed that
      the hydrocarbon sources were petrogenic, pyrogenic, and biogenic. Only a few PAHs
      exceeded the threshold effects level (TEL) guideline. Industrial activities are
      the presumed sources of metals and metalloids except for copper, which is from
      copper sulfate used as algaecide in the reservoir. The bioavailable
      concentrations of some metal and metalloid exceeded the TEL-PEL guidelines. The
      acid volatile sulfide concentration was greater than that of the simultaneously
      extracted metals in the clayey-silty reservoir sediments, whereas the opposite
      result was observed for the sandy sediments of the tributaries. The sediment
      interstitial water toxic units were >1 for metals, thus indicating that metals
      are potentially toxic to the benthos. Considering the data set generated in this
      study, it can be concluded that the degradation of Ibirite reservoir and its
      tributaries cannot be solely attributed to the input of hydrocarbons, but
      predominantly to the discharge of raw urban sewage and effluents from other
      industrial sources.

PMID- 24078049
TI  - Biomonitoring of cadmium, chromium, nickel and arsenic in general population
      living near mining and active industrial areas in Southern Tunisia.
AB  - The human health impact of the historic and current mining and industrial
      activities in Tunisia is not known. This study assessed the exposure to metals in
      the population of Southern Tunisia, using biomonitoring. The aim of this pilot
      study was to evaluate metal exposure on 350 participants living near mining and
      active industrial areas in the South of Tunisia. Blood specimens were analyzed
      for metals (Cd, Cr, As, and Ni) by Atomic Absorption Spectrometer equipped with
      Zeeman background correction and AS-800 auto sampler by graphite furnace and
      graphite tubes with integrated L'vov platform. The sample population was
      classified according to different age groups, sex, smoking habit, sea food and
      water drinking consumption, occupational exposure, amalgam fillings and place of
      residence. The blood As, Cd, Cr and Ni values expressed as mean +/- SD were 1.56
      +/- 2.49, 0.74 +/- 1.15, 35.04 +/- 26.02 and 30.56 +/- 29.96 MUg/l, respectively.
      Blood Cd and Ni levels in smokers were 2 and 1.2 times, respectively, higher than
      in non-smokers. Blood Cd levels increase significantly with age (p = 0.002). As,
      Cd and Ni were significantly correlated with gender and age (p < 0.05). Cd level
      in blood samples of subjects occupationally exposed was 1.3 times higher than
      that of non-exposed. Blood metals were not significantly affected by amalgam
      fillings, place of living and sea food and drinking water consumption. This first
      biomonitoring study of metal exposure in the South of Tunisia reveals a
      substantial exposure to several metals. The pathways of exposure and health
      significance of these findings need to be further investigated.

PMID- 24078051
TI  - Vegetation response to hydrologic and geomorphic factors in an arid region of the
      Baja California Peninsula.
AB  - Remotely sensed imageries were used to analyze the response of desert vegetation
      to physiographic factors and accumulated precipitation in drier and wetter years
      within a region of >16,500 km(2) sampled with 5,000 random pixels of 30 m.
      Vegetation development was indexed by the annual maximum values for greenness
      (SAVI) and canopy water content (NDII). Precipitation was interpolated from the
      0.25 degrees  grid of the Tropical Rainfall Measurement Mission satellite-based
      estimates, showing a regional average of ~55 mm in the wetter year. The
      vegetation indices were only weakly related to total precipitation, often in a
      negative sense. Terrain factors that most often affected the vegetation indices,
      in multiple regression models, were Topographic Wetness Index, elevation, and
      slope gradient; these often had different signs for SAVI and for NDII. Models for
      NDII on intrusive igneous rocks gave better results than on extrusive igneous
      rocks. The strongest patterns in vegetation development were the contrast among
      Pacific coast, Cordillera, and Gulf coast subregions and the generally stronger
      results for NDII than SAVI.

PMID- 24078052
TI  - Monitoring and risk assessment of pesticides in a tropical river of an
      agricultural watershed in northern Thailand.
AB  - The increasing application of pesticides in the uplands of northern Thailand has
      increased the transfer of pesticides to surface water. To assess the risk of
      pesticide use for stream water quality, we monitored the concentrations of seven
      pesticides (atrazine, dichlorvos, chlorpyrifos, dimethoate, chlorothalonil,
      (alpha-, beta-) endosulfan, cypermethrin) frequently used in the Mae Sa watershed
      (77 km(2)) in water and sediment samples over a period of one and a half years
      (2007-2008). All investigated pesticides were recorded in the river. Chlorpyrifos
      was detected most often in water samples (75% at the headwater station), while
      cypermethrin was most often found in riverbed (86%) and in all suspended sediment
      samples. The highest concentrations of the pesticides were detected during the
      rainy season. About 0.002 to 4.1% by mass of the applied pesticides was lost to
      surface water. The risk assessment was based on the risk characterization ratio
      (RCR). The RCRs of dichlorvos in water, (alpha-, beta-) endosulfan, and
      cypermethrin in water and sediments were higher than unity indicating that they
      are likely to pose a threat to aquatic ecosystem. Finally, we discuss the role of
      sampling design on ecotoxicological risk assessment. Our study shows that
      pesticide contamination of surface waters is an environmental issue in the Mae Sa
      watershed and that measures need to be undertaken to reduce the loss of
      pesticides from soil to surface waters.

PMID- 24078053
TI  - Artificial neural network modeling of dissolved oxygen in reservoir.
AB  - The water quality of reservoirs is one of the key factors in the operation and
      water quality management of reservoirs. Dissolved oxygen (DO) in water column is
      essential for microorganisms and a significant indicator of the state of aquatic
      ecosystems. In this study, two artificial neural network (ANN) models including
      back propagation neural network (BPNN) and adaptive neural-based fuzzy inference
      system (ANFIS) approaches and multilinear regression (MLR) model were developed
      to estimate the DO concentration in the Feitsui Reservoir of northern Taiwan. The
      input variables of the neural network are determined as water temperature, pH,
      conductivity, turbidity, suspended solids, total hardness, total alkalinity, and
      ammonium nitrogen. The performance of the ANN models and MLR model was assessed
      through the mean absolute error, root mean square error, and correlation
      coefficient computed from the measured and model-simulated DO values. The results
      reveal that ANN estimation performances were superior to those of MLR. Comparing
      to the BPNN and ANFIS models through the performance criteria, the ANFIS model is
      better than the BPNN model for predicting the DO values. Study results show that
      the neural network particularly using ANFIS model is able to predict the DO
      concentrations with reasonable accuracy, suggesting that the neural network is a
      valuable tool for reservoir management in Taiwan.

PMID- 24078054
TI  - Grading of cerebral glioma with multiparametric MR imaging and 18F-FDG-PET:
      concordance and accuracy.
AB  - OBJECTIVES: To retrospectively evaluate concordance rates and predictive values
      in concordant cases among multiparametric MR techniques and FDG-PET to grade
      cerebral gliomas. METHODS: Multiparametric MR imaging and FDG-PET were performed
      in 60 consecutive patients with cerebral gliomas (12 low-grade and 48 high-grade
      gliomas). As the dichotomic variables, conventional MRI, minimum apparent
      diffusion coefficient in diffusion-weighted imaging, maximum relative cerebral
      blood volume ratio in perfusion-weighted imaging, choline/creatine ratio and
      (lipid and lactate)/creatine ratio in MR spectroscopy, and maximum standardised
      uptake value ratio in FDG-PET in low- and high-grade gliomas were compared. Their
      concordance rates and positive/negative predictive values (PPV/NPV) in concordant
      cases were obtained for the various combinations of multiparametric MR techniques
      and FDG-PET. RESULTS: There were significant differences between low- and high
      grade gliomas in all techniques. Combinations of two, three, four, and five out
      of the five techniques showed concordance rates of 77.0 +/- 4.8%, 65.5 +/- 4.0%,
      58.3 +/- 2.6% and 53.3%, PPV in high-grade concordant cases of 97.3 +/- 1.7%,
      99.1 +/- 1.4%, 100.0 +/- 0% and 100.0% and NPV in low-grade concordant cases of
      70.2 +/- 7.5%, 78.0 +/- 6.0%, 80.3 +/- 3.4% and 80.0%, respectively. CONCLUSION:
      Multiparametric MR techniques and FDG-PET have a concordant tendency in a two
      tiered classification for the grading of cerebral glioma. If at least two
      examinations concordantly indicated high-grade gliomas, the PPV was about 95%.
      KEY POINTS: * Modern imaging techniques can help predict the aggressiveness of
      cerebral gliomas. * Multiparametric MRI and FDG-PET have a concordant tendency to
      grade cerebral gliomas. * Their high-grade concordant cases revealed at least 95
      % positive predictive values. * Their low-grade concordant cases revealed about
      70-80% negative predictive values.

PMID- 24078055
TI  - 3-T breast magnetic resonance imaging in patients with suspicious
      microcalcifications on mammography.
AB  - OBJECTIVE: To investigate the diagnostic value of 3-Tesla (T) breast MRI in
      patients presenting with microcalcifications on mammography. METHODS: Between
      January 2006 and May 2009, 123 patients with mammographically detected BI-RADS 3
      5 microcalcifications underwent 3-T breast MRI before undergoing breast biopsy.
      All MRIs of the histopathologically confirmed index lesions were reviewed by two
      breast radiologists. The detection rate of invasive carcinoma and ductal
      carcinoma in situ (DCIS) was evaluated, as well as the added diagnostic value of
      MRI over mammography and breast ultrasound. RESULTS: At pathology, 40/123 (33%)
      lesions proved malignant; 28 (70%) DCIS and 12 (30%) invasive carcinoma. Both
      observers detected all invasive malignancies at MRI, as well as 79% (observer 1)
      and 86% (observer 2) of in situ lesions. MRI in addition to conventional imaging
      led to a significant increase in area under the receiver operating characteristic
      (ROC) curve from 0.67 (95% CI 0.56-0.79) to 0.79 (95% CI 0.70-0.88, observer 1)
      and to 0.80 (95% CI 0.71-0.89, observer 2), respectively. CONCLUSIONS: 3-T breast
      MRI was shown to add significant value to conventional imaging in patients
      presenting with suspicious microcalcifications on mammography. KEY POINTS: * 3-T
      MRI is increasingly used for breast imaging in clinical practice. * On 3-T breast
      MRI up to 86% of DCIS lesions are detected. * 3-T MRI increases the diagnostic
      value in patients with mammographically detected microcalcifications.

PMID- 24078056
TI  - Objectively assessed sedentary time and type 2 diabetes mellitus: a case-control
      study.

PMID- 24078057
TI  - Matrix metalloproteinase-10 plays an active role in microvascular complications
      in type 1 diabetic patients.
AB  - AIMS/HYPOTHESIS: The role of metalloproteinase-10 (MMP-10) in type 1 diabetes is
      not known. We hypothesise that it plays a role in the onset and progression of
      diabetic nephropathy and retinopathy. METHODS: Serum MMP-10 levels from 269
      patients with type 1 diabetes were measured, and their association with
      microvascular complications was analysed. We also studied whether knocking out
      the Mmp10 gene influenced the extent of renal injury and retinal damage in a
      streptozotocin-induced diabetic mouse model. RESULTS: The risk of nephropathy and
      proliferative retinopathy associated with the highest vs the lowest MMP-10
      tertile was increased three to four times independently of the classical risk
      factors. Accordingly, renal function and morphology were better preserved in
      diabetic Mmp10 -/- mice than in their Mmp10 +/+ counterparts. There were more
      kidney-infiltrating macrophages in diabetic Mmp10+/+ mice, suggesting that MMP-10
      contributes to the inflammatory response leading to microvascular complications.
      The loss of neuronal cells in the retinas of diabetic Mmp10 +/+ mice was higher
      than in Mmp10 -/- mice. Retinal inflammation was decreased in Mmp10 -/- mice, as
      indicated by their reduced retinal caspase-1 levels. CONCLUSIONS/INTERPRETATION:
      MMP-10 is involved in the development of microvascular complications in type 1
      diabetes and emerges as a potential therapeutic target for slowing down the
      evolution of diabetic nephropathy and retinopathy.

PMID- 24078058
TI  - Increased circulating levels of betatrophin in individuals with long-standing
      type 1 diabetes.
AB  - AIMS/HYPOTHESIS: The hormone betatrophin was recently described as a potent
      stimulator of beta cell proliferation in mice. Insulin resistance, but not
      insulin deficiency, caused upregulation of betatrophin expression. If these
      findings were found to be fully applicable in humans, this would open up the
      possibility of future betatrophin treatment in type 1 diabetes. The present study
      measured for the first time betatrophin concentrations in humans and tested the
      hypothesis that there would be no difference in circulating betatrophin
      concentrations between patients with type 1 diabetes and healthy individuals.
      METHODS: Betatrophin concentrations in plasma of 33 patients with type 1 diabetes
      and 24 age-matched healthy controls were measured by ELISA. The study
      participants were characterised for blood lipids, BMI, plasma glucose and HbA1c,
      and, for the diabetic patients, their insulin requirements and any residual C
      peptide concentrations. RESULTS: Plasma betatrophin concentrations were normally
      ~300 pg/ml, but were approximately doubled in patients with type 1 diabetes. In
      the patients, there were no correlations between betatrophin and age, blood
      lipids, BMI, glucose control or insulin requirement, whereas in controls
      betatrophin levels increased with age. BMI, blood pressure and triacylglycerol,
      LDL-cholesterol and HDL-cholesterol levels were similar in patients and healthy
      controls. CONCLUSIONS/INTERPRETATION: Circulating concentrations of betatrophin
      are increased in type 1 diabetes in contrast with what was recently described in
      an insulin-deficient mouse model. However, increased betatrophin concentrations
      do not protect against loss of C-peptide. Betatrophin treatment in type 1
      diabetes would therefore probably not be successful without the use of
      supraphysiological doses or a combination with immune regulatory treatment.

PMID- 24078059
TI  - Leptin resistance and obesity in mice with deletion of methyl-CpG-binding protein
      2 (MeCP2) in hypothalamic pro-opiomelanocortin (POMC) neurons.
AB  - AIMS/HYPOTHESIS: Pro-opiomelanocortin (POMC) neurons in the arcuate nucleus (ARC)
      regulate energy homeostasis by secreting alpha-melanocyte-stimulating hormone
      (alpha-MSH), derived from POMC precursor, in response to leptin signalling.
      Expression of Pomc is subject to multiple modes of regulation, including
      epigenetic regulation. Methyl-CpG-binding protein 2 (MeCP2), a nuclear protein
      essential for neuronal function, interacts with promoters to influence gene
      expression. We aim to address whether MeCP2 regulates hypothalamic Pomc
      expression and to investigate the role of epigenetics, particularly DNA
      methylation, in this process. METHODS: We generated a mouse line with MeCP2
      specifically deleted in POMC neurons (Mecp2 flox/y /Pomc-Cre [PKO]) and
      characterised its metabolic phenotypes. We examined the DNA methylation pattern
      of the Pomc promoter and its impact on hypothalamic gene expression. We also
      studied the requirement of MeCP2 for, and the effects of, DNA methylation on Pomc
      promoter activity using luciferase assays. RESULTS: PKO mice are overweight, with
      increased fat mass resulting from increased food intake and respiratory exchange
      ratio. PKO mice also exhibit elevated plasma leptin. Deletion of MeCP2 in POMC
      neurons leads to increased DNA methylation of the hypothalamic Pomc promoter and
      reduced Pomc expression. Furthermore, in vitro studies show that hypermethylation
      of the Pomc promoter reduces its transcriptional activity and reveal a functional
      synergy between MeCP2 and cAMP responsive element binding protein 1 (CREB1) in
      positively regulating the Pomc promoter. CONCLUSIONS/INTERPRETATION: Our results
      demonstrate that MeCP2 positively regulates Pomc expression in the hypothalamus.
      Absence of MeCP2 in POMC neurons leads to increased DNA methylation of the Pomc
      promoter, which, in turn, downregulates Pomc expression, leading to obesity in
      mice with an accentuating degree of leptin resistance.

PMID- 24078060
TI  - Continuity of Care in Children's Mental Health: development of a measure.
AB  - A new measure, Continuity of Care in Children's Mental Health (C3MH), is
      presented. The study involved item generation, pre-testing, pilot testing, and
      validation. The C3MH was administered to 364 parents recruited from 13 children's
      mental health agencies in Ontario, Canada. The measure includes five scales
      supported by confirmatory factor analysis. Scale validity was supported through
      analyses of relationships with established measures of satisfaction, problem
      severity, and therapeutic alliance, as well as through known-group differences.
      The results of a pilot youth-report version (N = 57) are presented. The C3MH will
      be a useful tool for assessing improvements in system integration.

PMID- 24078061
TI  - Pyrithiamine-induced thiamine deficiency alters proliferation and neurogenesis in
      both neurogenic and vulnerable areas of the rat brain.
AB  - Thiamine deficiency (TD) leads to Wernicke's encephalopathy (WE), in which focal
      histological lesions occur in periventricular areas of the brain. Recently,
      impaired neurogenesis has been reported in the hippocampus during the dietary
      form of TD, and in pyrithiamine-induced TD (PTD), a well-characterized model of
      WE. To further characterize the consequences of PTD on neural stem/progenitor
      cell (NSPC) activity, we have examined the effect of this treatment in the rat on
      both the subventricular zone (SVZ) of the rostral lateral ventricle and
      subgranular layer (SGL) of the hippocampus, and in the thalamus and inferior
      colliculus, two vulnerable brain regions in this disorder. In both the SVZ and
      SGL, PTD led to a decrease in the numbers of bromodeoxyuridine-stained cells,
      indicating that proliferation of NSPCs destined for neurogenesis in these areas
      was reduced. Doublecortin (DCX) immunostaining in the SGL was decreased,
      indicating a reduction in neuroblast formation, consistent with impaired NSPC
      activity. DCX labeling was not apparent in focal areas of vulnerability. In the
      thalamus, proliferation of cells was absent while in the inferior colliculus,
      numerous actively dividing cells were apparent, indicative of a differential
      response between these two brain regions. Exposure of cultured neurospheres to
      PTD resulted in decreased proliferation of NSPCs, consistent with our in vivo
      findings. Together, these results indicate that PTD considerably affects cell
      proliferation and neurogenesis activity in both neurogenic areas and parts of the
      brain known to display structural and functional vulnerability, confirming and
      extending recent findings on the effects of TD on neurogenesis. Future use of
      NSPCs in vitro may allow a closer and more detailed examination of the
      mechanism(s) underlying inhibition of these cells during TD.

PMID- 24078063
TI  - Impact of therapeutic regimen and clinical presentation on overall survival in
      CNS lymphoma.
AB  - BACKGROUND: The authors present a retrospective analysis of 45 patients who
      underwent treatment of CNS lymphoma (both primary and secondary) at a single
      institution between 2005 and 2012. METHODS: This study involves 21 female and 24
      male patients with a mean age of 59.2 years. All medical records and pathology
      reports were reviewed for each patient. Univariate and multivariate analyses of
      overall survival were performed. RESULTS: Presentation with altered mental status
      was a significant risk factor for worse overall survival. An HIV infection, deep
      lesion location, and age over 60 did not impact survival. A survival benefit was
      demonstrated with the use of systemic therapy, specifically rituximab, and
      radiation. The CNS Lymphoma Score was derived from this cohort, which proved a
      powerful predictive tool for overall survival. The surgical complication rate in
      this series was 17.8 %. CONCLUSIONS: This study highlights the prognostic
      importance of presenting mental status on outcomes in CNS lymphoma and
      demonstrates a summative benefit of rituximab and whole brain radiation therapy.
      Considering these factors together provides an easily applicable and meaningful
      stratification for this patient population. The surgical complication rate in
      this patient population is not negligible. The high percentage of wound-related
      surgical complications suggests the need for a waiting period between surgery and
      initiation of chemotherapy to allow for wound healing.

PMID- 24078064
TI  - Postsurgical screening for psychosocial disorders in neurooncological patients.
AB  - BACKGROUND: The diagnosis of a brain tumor can cause severe psychosocial
      distress, which can have a variety of negative consequences on patients' physical
      and mental well-being. The detection of psychosocial distress in daily clinical
      routine is difficult and subsequent referral to mental health professionals is
      rare. The aim of this study was to determine the incidence of psychological
      disorders of patients early postoperatively and to investigate both the Hornheide
      Screening Instrument (HSI) and Distress Thermometer (DT) as screening tools in
      neurooncological practice. METHODS: One hundred and thirty-four patients with
      brain tumors of different histology were postoperatively evaluated by the
      Distress Thermometer and Hornheide Screening Instrument. Additionally,
      correlation to gender, age, localization of the tumor, Karnofsky performance
      score and tumor entity were analyzed. RESULTS: After initial surgery 36 patients
      (26.9 %) showed pathologic results in the HSI and 50 patients (36.7 %) were
      severely distressed (DT Score>=6). Women had the highest rate of psychological
      disorders, followed by patients suffering from gliomas and meningiomas. Further
      highlighting the results of both tests, over 80 % of those patients who scored
      pathologically in both tests were in need of professional psychiatric help due to
      depression. CONCLUSION: Both the DT and HSI are suitable instruments for
      identifying patients in psychological distress after brain tumor surgery in
      neurooncological routine. Our results confirm that nearly one third of patients
      are unable to overcome the difficulties facing the diagnosis of a brain tumor in
      this early situation and should be supported by mental health professionals.

PMID- 24078062
TI  - Determinants of virulence of influenza A virus.
AB  - Influenza A viruses cause yearly seasonal epidemics and occasional global
      pandemics in humans. In the last century, four human influenza A virus pandemics
      have occurred. Occasionally, influenza A viruses that circulate in other species
      cross the species barrier and infect humans. Virus reassortment (i.e. mixing of
      gene segments of multiple viruses) and the accumulation of mutations contribute
      to the emergence of new influenza A virus variants. Fortunately, most of these
      variants do not have the ability to spread among humans and subsequently cause a
      pandemic. In this review, we focus on the threat of animal influenza A viruses
      which have shown the ability to infect humans. In addition, genetic factors which
      could alter the virulence of influenza A viruses are discussed. The
      identification and characterisation of these factors may provide insights into
      genetic traits which change virulence and help us to understand which genetic
      determinants are of importance for the pandemic potential of animal influenza A
      viruses.

PMID- 24078065
TI  - A-trains for intraoperative monitoring in patients with recurrent vestibular
      schwannoma.
AB  - BACKGROUND: Second surgery of recurrent vestibular schwannoma (VS) after previous
      surgery, stereotactic radiosurgery (SR) or fractionated radiotherapy (FR) carries
      an increased risk for deterioration of facial nerve function, e.g., due to
      adhesions, underlining the need for intraoperative monitoring. Facial "Atrain"
      EMG activity ("traintime") correlates with the degree of postoperative facial
      palsy. Studies investigating A-trains in VS patients with previous surgery, SR or
      FR are missing. We therefore investigated the value of A-train monitoring in
      patients undergoing second surgery for VS. METHOD: Intraoperative EMG data from
      patients who underwent second surgery for VS after previous surgery, SR and/or FR
      at our institution between 2006 and 2012 were retrospectively analyzed. Ten
      patients were selected (5 male): Seven had previous SR/RT and MS, three previous
      surgery only. Traintime values and distribution was compared to published
      thresholds and to 77 patients who underwent first surgery for VS during the same
      time period. RESULTS: A-trains were recorded early after opening of the dura,
      before facial nerve preparation. Mean traintime was 46.9 s (18.51 s - 80.82 s) in
      patients with previous SR/RT. In patients with previous MS only, traintime was
      0.06 s, 0.99 s and 22.46 s. Compared to the literature, traintime was higher than
      expected in six patients (four with previous SR/RT, two without), respectively
      seven compared to the 77 patients with first surgery (5 SR/RT). Seven patients
      with previous SR/RT and none with previous surgery showed diffuse A-train
      distributions without significant percentages in single channels, compared to 60
      of 77 patients with first surgery (p <0.02). CONCLUSIONS: Especially SR/RT, but
      also previous surgery seems to induce changes in the facial nerve leading to
      hyperexcitability and exceedingly high traintime values. Based on these findings,
      A-train monitoring in this specific patient group should be interpreted with
      caution.

PMID- 24078066
TI  - Depression and insomnia in cancer: prevalence, risk factors, and effects on
      cancer outcomes.
AB  - Over two-thirds of the 11.4 million cancer survivors in the United States can
      expect long-term survival, with many others living with cancer as a chronic
      disease controlled by ongoing therapy. Behavioral comorbidities often arise
      during treatment and persist long term to complicate survival and reduce quality
      of life. This review focuses on depression and insomnia with an emphasis on
      understanding the role of cancer-specific factors and their contribution to the
      prevalence of these behavioral comorbidities in cancer patients following cancer
      diagnosis and treatment. The clinical significance of depression and insomnia for
      cancer patients is further stressed by epidemiological observations that link
      depression and insomnia to cancer morbidity and mortality risk. 

PMID- 24078067
TI  - Mindfulness and acceptance-based behavioral therapies for anxiety disorders.
AB  - This article presents a brief conceptual overview of acceptance-based behavioral
      therapies (ABBTs) for anxiety disorders, followed by a review and summary of the
      recent efficacy studies of ABBTs for anxiety and comorbid disorders. We discuss
      clinical implications, including the importance of targeting reactivity and
      experiential avoidance in interventions for anxiety disorders through the use of
      mindfulness and other acceptance-based strategies, as well the encouragement of
      engagement in meaningful activities or valued action. We also address future
      directions for research, such as expanding research to include more randomized
      control trials comparing ABBTs for specific anxiety disorders to other active
      treatments, examining mechanisms of change, exploring adaptations in different
      care-delivery contexts, as well as determining the applicability of these
      approaches to clients from marginalized or non-dominant statuses.

PMID- 24078068
TI  - Group III metabotropic glutamate receptors and drug addiction.
AB  - Neuroadaptations of glutamatergic transmission in the limbic reward circuitry are
      linked to persistent drug addiction. Accumulating data have demonstrated roles of
      ionotropic glutamate receptors and group I and II metabotropic glutamate
      receptors (mGluRs) in this event. Emerging evidence also identifies Galphai/o
      coupled group III mGluRs (mGluR4/7/8 subtypes enriched in the limbic system) as
      direct substrates of drugs of abuse and active regulators of drug action. Auto-
      and heteroreceptors of mGluR4/7/8 reside predominantly on nerve terminals of
      glutamatergic corticostriatal and GABAergic striatopallidal pathways,
      respectively. These presynaptic receptors regulate basal and/or phasic release of
      respective transmitters to maintain basal ganglia homeostasis. In response to
      operant administration of common addictive drugs, such as psychostimulants
      (cocaine and amphetamine), alcohol and opiates, limbic group III mGluRs undergo
      drastic adaptations to contribute to the enduring remodeling of excitatory
      synapses and to usually suppress drug seeking behavior. As a result, a loss-of
      function mutation (knockout) of individual group III receptor subtypes often
      promotes drug seeking. This review summarizes the data from recent studies on
      three group III receptor subtypes (mGluR4/7/8) expressed in the basal ganglia and
      analyzes their roles in the regulation of dopamine and glutamate signaling in the
      striatum and their participation in the addictive properties of three major
      classes of drugs (psychostimulants, alcohol, and opiates).

PMID- 24078075
TI  - Cigarette brand loyalty in Australia: findings from the ITC Four Country Survey.
AB  - BACKGROUND AND AIM: There is little academic research on tobacco brand loyalty
      and switching, and even less in restrictive marketing environments such as
      Australia. This paper examines tobacco brand family loyalty, reasons for choice
      of brand and the relation between these and sociodemographic variables over a
      period of 10 years in Australia. METHODS: Data from current Australian smokers
      from 9 waves of the International Tobacco Control Policy Evaluation 4-Country
      Survey covering the period from 2002 to early 2012. Key measures reported were
      having a regular brand, use for at least 1 year, brand stability (derived from
      same reported brand at successive waves), and reasons for choosing brands.
      RESULTS: Measures of brand loyalty showed little change across the period, with
      around 80% brand stability and 95% reporting a regular brand. Older adults were
      more brand-loyal than those under 25. Young people's brand choice was influenced
      more by friends, whereas older adults were more concerned about health. Price was
      the most reported reason for brand switching. Those in the higher income tertiles
      showed more loyalty than those in the lowest. The least addicted smokers also
      showed less brand loyalty. We found no clear relationship between brand loyalty
      and policies that were implemented to affect tobacco use. CONCLUSIONS: Levels of
      brand loyalty in Australia are quite high and consistent, and do not appear to
      have been influenced greatly by changes in tobacco control policies.

PMID- 24078076
TI  - Who purchases cigarettes from cheaper sources in China? Findings from the ITC
      China Survey.
AB  - OBJECTIVE: The availability of cigarettes from cheaper sources constitutes a
      major challenge to public health throughout the world, including China, because
      it may counteract price-based tobacco control policies. The goal of this study
      was to identify factors associated with purchasing cigarettes from cheaper
      sources among adult smokers in China. METHODS: Data were analysed from Waves 1 to
      3 of the International Tobacco Control China Survey conducted in 2006-2009 among
      adult smokers in six cities in China (N=7980). One survey question asked, "In the
      last 6 months, have you purchased cheaper cigarettes than you can get from local
      stores for economic reasons?" We examined whether sociodemographic factors and
      smoking intensity were associated with purchasing cigarettes from cheaper sources
      using the general estimating equations model. Sociodemographic factors considered
      were gender, age, marital status, monthly household income, education, employment
      status and city of residence. RESULTS: 15.6% of smokers reported purchasing
      cigarettes from cheaper sources. After controlling for other covariates, the
      associations of the behaviour of purchasing cigarettes from cheaper sources with
      age (adjusted OR (AOR)=1.49, 95% CI 1.17 to 3.92 for age 18-24 compared with age
      55+) and with income (AOR=2.93, 95% CI 2.27 to 3.79 for low income compared with
      high income) were statistically significant, but there was no statistically
      significant relationship with smoking intensity. CONCLUSIONS: Our findings
      indicate that young and low-income smokers are more likely than older and high
      income smokers to purchase cigarettes from cheaper sources in China. Tobacco
      control policies that reduce the availability of cigarettes from cheaper sources
      could have an impact on reducing cigarette consumption among young and low-income
      smokers in China.

PMID- 24078078
TI  - Leading the Herd Astray: An Experimental Study of Self-Fulfilling Prophecies in
      an Artificial Cultural Market.
AB  - Individuals influence each others' decisions about cultural products such as
      songs, books, and movies; but to what extent can the perception of success become
      a "self-fulfilling prophecy"? We have explored this question experimentally by
      artificially inverting the true popularity of songs in an online "music market,"
      in which 12,207 participants listened to and downloaded songs by unknown bands.
      We found that most songs experienced self-fulfilling prophecies, in which
      perceived-but initially false-popularity became real over time. We also found,
      however, that the inversion was not self-fulfilling for the market as a whole, in
      part because the very best songs recovered their popularity in the long run.
      Moreover, the distortion of market information reduced the correlation between
      appeal and popularity, and led to fewer overall downloads. These results,
      although partial and speculative, suggest a new approach to the study of cultural
      markets, and indicate the potential of web-based experiments to explore the
      social psychological origin of other macro-sociological phenomena.

PMID- 24078077
TI  - Reduction in Golgi apparatus dimension in the absence of a residential protein, N
      acetylglucosaminyltransferase V.
AB  - Various proteins are involved in the generation and maintenance of the membrane
      complex known as the Golgi apparatus. We have used mutant Chinese hamster ovary
      (CHO) cell lines Lec4 and Lec4A lacking N-acetylglucosaminyltransferase V
      (GlcNAcT-V, MGAT5) activity and protein in the Golgi apparatus to study the
      effects of the absence of a single glycosyltransferase on the Golgi apparatus
      dimension. Quantification of immunofluorescence in serial confocal sections for
      Golgi alpha-mannosidase II and electron microscopic morphometry revealed a
      reduction in Golgi volume density up to 49 % in CHO Lec4 and CHO Lec4A cells
      compared to parental CHO cells. This reduction in Golgi volume density could be
      reversed by stable transfection of Lec4 cells with a cDNA encoding Mgat5.
      Inhibition of the synthesis of beta1,6-branched N-glycans by swainsonine had no
      effect on Golgi volume density. In addition, no effect on Golgi volume density
      was observed in CHO Lec1 cells that contain enzymatically active GlcNAcT-V, but
      cannot synthesize beta1,6-branched glycans due to an inactive GlcNAcT-I in their
      Golgi apparatus. These results indicate that it may be the absence of the GlcNAcT
      V protein that is the determining factor in reducing Golgi volume density. No
      dimensional differences existed in cross-sectioned cisternal stacks between Lec4
      and control CHO cells, but significantly reduced Golgi stack hits were observed
      in cross-sectioned Lec4 cells. Therefore, the Golgi apparatus dimensional change
      in Lec4 and Lec4A cells may be due to a compaction of the organelle.

PMID- 24078079
TI  - Do climatic conditions affect host and parasite phenotypes differentially? A case
      study of magpies and great spotted cuckoos.
AB  - Climatic conditions, through their effects on resource availability, may affect
      important life history strategies and trade-offs in animals, as well as their
      interactions with other organisms such as parasites. This impact may depend on
      species-specific pathways of development that differ even among species with
      similar resource requirements (e.g., avian brood parasites and their hosts). Here
      we explore the degree of covariation between environmental-climatic conditions
      and nestling phenotypes (i.e., tarsus length, body mass, immune response to
      phytohemagglutinin injection) and ectoparasite loads of great spotted cuckoos
      (Clamator glandarius) and those of their magpie (Pica pica) hosts, both within
      and among 11 study years (1997-2011). Our main results were that (1) nestling
      phenotypes differed among years, but differently for great spotted cuckoos and
      magpies; (2) nestling phenotypes showed significant among-year covariation with
      breeding climatic conditions (temperature and precipitation); and (3) these
      associations differed for cuckoos and magpies for some phenotypic traits. As the
      average temperature at the beginning of the breeding season (April) increased,
      body mass and tarsus length increased only for cuckoos, but not for magpie hosts,
      while immune response decreased in both species. Finally, (4) the strength of the
      within-year relationships between the probability of ectoparasitism by Carnus
      hemapterus flies and laying date (used as an estimate of the within-year
      variation in climatic conditions) was negatively affected by the annual
      accumulated precipitation in April. These results strongly suggest that variation
      in climatic conditions would result in asymmetric effects on different species
      with respect to the probability of ectoparasitism, immunity and body size. Such
      asymmetric effects may affect animal interactions in general and those of brood
      parasites and their hosts in particular.

PMID- 24078080
TI  - The influence of ambient ultraviolet light on sperm quality and sexual
      ornamentation in three-spined sticklebacks (Gasterosteus aculeatus).
AB  - Exposure to enhanced levels of ambient ultraviolet (UV) radiation (UVR) can have
      adverse effects on aquatic organisms including damage at the cellular and
      molecular level and impairment of development, fecundity and survival. Much
      research has been conducted on the role of the harmful UVB radiation. However,
      due to its greater penetration in water the more abundant UVA radiation can also
      act as an environmental stressor. Little is known about UVR effects on sperm
      characteristics although sperm cells should be especially prone to UV-induced
      oxidative stress. Moreover, UV-related changes in oxidative status may affect the
      phenotypic expression of energetically costly sexual ornaments. We investigated
      the effects of long-term exposure to ecologically relevant levels of simulated
      UVA radiation on sperm quality and sexual ornamentation in three-spined
      sticklebacks (Gasterosteus aculeatus). Males were assigned to three spectral
      exposure treatments differing in the UV spectral part so that they received
      either enhanced, moderate or no UVA radiation. The results reveal that exposure
      to enhanced ambient UVA levels had detrimental effects on both male breeding
      coloration and sperm velocity providing evidence that UVR affects traits targeted
      by pre- and post-copulatory sexual selection. By highlighting the role of UVA as
      a factor influencing fitness-relevant traits, our findings may contribute to a
      better understanding of the consequences of current and future levels of solar
      UVR for mating systems and life history.

PMID- 24078081
TI  - Propagule pressure-invasibility relationships: testing the influence of soil
      fertility and disturbance with Lespedeza cuneata.
AB  - Although invasion risk is expected to increase with propagule pressure (PP), it
      is unclear whether PP-invasibility relationships follow an asymptotic or some
      other non-linear form and whether such relationships vary with underlying
      environmental conditions. Using manipulations of PP, soil fertility and
      disturbance, we tested how each influence PP-invasibility relationships for
      Lespedeza cuneata in a Kansas grassland and use recruitment curve models to
      determine how safe sites may contribute to plant invasions. After three growing
      seasons, we found that the PP-invasibility relationships best fit an asymptotic
      model of invasion reflecting a combination of density-independent and density
      dependent processes and that seeds were aggregated within the plant community
      despite efforts to uniformly sow seeds. Consistent with some models, community
      invasibility decreased with enhanced soil fertility or reduced levels of
      disturbance in response to changes in the fraction of safe sites. Our results
      illustrate that disturbance and soil fertility can be a useful organizing
      principle for predicting community invasibility, asymptotic models are a
      reasonable starting point for modeling invasion, and new modeling techniques
      coupled with classic experimental approaches-can enhance our understanding of the
      invasion process.

PMID- 24078082
TI  - Nutrient resorption of two evergreen shrubs in response to long-term
      fertilization in a bog.
AB  - Plant resorption of multiple nutrients during leaf senescence has been
      established but stoichiometric changes among N, P and K during resorption and
      after fertilization are poorly understood. We anticipated that increased N supply
      would lead to further P limitation or co-limitation with N or K [i.e. P
      (co)limitation], decrease N resorption and increase P and K resorption, while P
      and K addition would decrease P and K resorption and increase N resorption.
      Furthermore, Ca would accumulate while Mg would be resorbed during leaf
      senescence, irrespective of fertilization. We investigated the effect of N, P and
      K addition on resorption in two evergreen shrubs (Chamaedaphne calyculata and
      Rhododendron groenlandicum) in a long-term fertilization experiment at Mer Bleue
      bog, Ontario, Canada. In general, N addition caused further P-(co)limitation,
      increased P and K resorption efficiency but did not affect N resorption. P and K
      addition did not shift the system to N limitation and affect K resorption, but
      reduced P resorption proficiency. C. calyculata resorbed both Ca and Mg while R.
      groenlandicum resorbed neither. C. calyculata showed a higher resorption than R.
      groenlandicum, suggesting it is better adapted to nutrient deficiency than R.
      groenlandicum. Resorption during leaf senescence decreased N:P, N:K and K:P
      ratios. The limited response of N and K and the response of P resorption to
      fertilization reflect the stoichiometric coupling of nutrient cycling, which
      varies among the two shrub species; changes in species composition may affect
      nutrient cycling in bogs.

PMID- 24078083
TI  - Comparison of serious adverse reactions between thalidomide and lenalidomide:
      analysis in the French Pharmacovigilance database.
AB  - Thalidomide and lenalidomide are structural analogs and immunomodulatory drugs.
      Lenalidomide appears to have a different safety profile than thalidomide and
      could be less toxic, and as far as we know, we did not found any study comparing
      their safety profile. The objective of our study was to review and compare
      serious adverse drug reactions (SADRs) of thalidomide and lenalidomide
      spontaneously reported to the French Pharmacovigilance database. We extracted all
      medically confirmed spontaneous reports of SADR for lenalidomide-based regimens
      and thalidomide-based regimens from the French Pharmacovigilance database. A
      "serious" adverse drug reaction (ADR) was defined as an ADR that is fatal or life
      threatening, which causes hospitalization or prolongation of hospitalization, or
      permanent or significant disability. The study period was between marketing of 2
      drugs and January 15, 2012. A total of 392 SADRs related to thalidomide-based
      regimens were identified in 244 patients and 377 SADRs related to lenalidomide
      based regimens in 220 patients. In spite of their structural analogy, this study
      highlights interesting differences between lenalidomide and thalidomide's safety
      profile: nervous system and vascular disorders are more frequent with thalidomide
      based regimens while hematologic, skin, infectious disorders and secondary
      primary cancers are more frequent with lenalidomide-based regimens. 

PMID- 24078084
TI  - The enzyme engineering of mutant homodimer and heterodimer of coproporphyinogen
      oxidase contributes to new insight into hereditary coproporphyria and
      harderoporphyria.
AB  - Hereditary coproporphyria (HCP) is an autosomal dominant-inherited disease of
      haem biosynthesis caused by partial deficiency of the enzyme coproporphyrinogen
      oxidase (CPOX). Patients with HCP show <50% of normal activity and those with the
      rare autosomal recessive harderoporphyria accumulate harderoporphyrinogen, an
      intermediate porphyrin of the CPOX reaction. To clarify the relationship of the
      low enzyme activity with these diseases, we expressed mutant CPOX carrying His
      tag from these porphyria patients and co-expressed mutant CPOX carrying His-tag
      and normal CPOX carrying HA-tag in a tandem fashion in Escherichia coli.
      Purification of the His-tag-containing enzyme revealed that the His-enzyme forms
      a heterodimer in association with the HA-enzyme, and analysis using a cross-link
      reagent confirmed that the enzyme is a dimer (~70 kDa). Then, we expressed homo-
      and heterodimers composed of the wild-type (wt) and engineered mutants of the
      enzyme or mutants from HCP patients. The monomer form of mutated CPOX did not
      show any activity and homodimeric enzymes derived from HCP mutant showed low
      activity (<20% of the control). Some mutations of amino acids 401-404 were
      associated with marked accumulation of harderoporphyrinogen, with a decrease in
      the production of protoporphyrinogen, whereas K404E derived from patients with
      harderoporphyria produced less harderoporphyrinogen. The heterodimers with wt and
      mutated subunits from HCP patients showed low protoporphyrinogen producing
      activity. These results show that the substitution of amino acids from R401 to
      K404 results in extremely low enzyme activity with either mutant homodimer or
      heterodimers containing normal and mutated subunits and can be linked to HCP
      disease. 

PMID- 24078085
TI  - Computational prediction and experimental validation of microRNAs in the brown
      alga Ectocarpus siliculosus.
AB  - We used an in silico approach to predict microRNAs (miRNAs) genome-wide in the
      brown alga Ectocarpus siliculosus. As brown algae are phylogenetically distant
      from both animals and land plants, our approach relied on features shared by all
      known organisms, excluding sequence conservation, genome localization and pattern
      of base-pairing with the target. We predicted between 500 and 1500 miRNAs
      candidates, depending on the values of the energetic parameters used to filter
      the potential precursors. Using quantitative polymerase chain reaction assays, we
      confirmed the existence of 22 miRNAs among 72 candidates tested, and of 8
      predicted precursors. In addition, we compared the expression of miRNAs and their
      precursors in two life cycle states (sporophyte, gametophyte) and under salt
      stress. Several miRNA precursors, Argonaute and DICER messenger RNAs were
      differentially expressed in these conditions. Finally, we analyzed the gene
      organization and the target functions of the predicted candidates. This showed
      that E. siliculosus miRNA genes are, like plant miRNA genes, rarely clustered
      and, like animal miRNA genes, often located in introns. Among the predicted
      targets, several widely conserved functional domains are significantly
      overrepresented, like kinesin, nucleotide-binding/APAF-1, R proteins and CED-4
      (NB-ARC) and tetratricopeptide repeats. The combination of computational and
      experimental approaches thus emphasizes the originality of molecular and cellular
      processes in brown algae. 

PMID- 24078086
TI  - Rapid construction of insulated genetic circuits via synthetic sequence-guided
      isothermal assembly.
AB  - In vitro recombination methods have enabled one-step construction of large DNA
      sequences from multiple parts. Although synthetic biological circuits can in
      principle be assembled in the same fashion, they typically contain repeated
      sequence elements such as standard promoters and terminators that interfere with
      homologous recombination. Here we use a computational approach to design
      synthetic, biologically inactive unique nucleotide sequences (UNSes) that
      facilitate accurate ordered assembly. Importantly, our designed UNSes make it
      possible to assemble parts with repeated terminator and insulator sequences, and
      thereby create insulated functional genetic circuits in bacteria and mammalian
      cells. Using UNS-guided assembly to construct repeating promoter-gene-terminator
      parts, we systematically varied gene expression to optimize production of a
      deoxychromoviridans biosynthetic pathway in Escherichia coli. We then used this
      system to construct complex eukaryotic AND-logic gates for genomic integration
      into embryonic stem cells. Construction was performed by using a standardized
      series of UNS-bearing BioBrick-compatible vectors, which enable modular assembly
      and facilitate reuse of individual parts. UNS-guided isothermal assembly is
      broadly applicable to the construction and optimization of genetic circuits and
      particularly those requiring tight insulation, such as complex biosynthetic
      pathways, sensors, counters and logic gates. 

PMID- 24078087
TI  - Changes in transcriptional pausing modify the folding dynamics of the pH
      responsive RNA element.
AB  - Previously, we described a novel pH-responsive RNA element in Escherichia coli
      that resides in the 5' untranslated region of the alx gene and controls its
      translation in a pH-dependent manner. Under normal growth conditions, this RNA
      region forms a translationally inactive structure, but when transcribed under
      alkaline conditions, it forms an active structure producing the Alx protein. We
      identified two distinct transcriptional pause sites and proposed that pausing at
      these sites interfered with the formation of the inactive structure while
      facilitating folding of the active one. Alkali increases the longevity of pausing
      at these sites, thereby promoting folding of the translationally active form of
      alx RNA. We show here that mutations that modify the extent and/or position of
      pausing, although silent with regard to structure stability per se, greatly
      influence the dynamics of folding and thereby translation. Our data illustrate
      the mechanistic design of alx regulation, relying on precise temporal and spatial
      characteristics. We propose that this unique design provides an opportunity for
      environmental signals such as pH to introduce structural changes in the RNA and
      thereby modulate expression. 

PMID- 24078088
TI  - The adaptive potential of hybridization demonstrated with bacteriophages.
AB  - The success or failure of hybrids and the factors that determine their fitness
      have ecological, evolutionary, medical, and economic implications. Hybrid fitness
      is a major determinant of the size of hybrid zones and the maintenance of related
      species with overlapping ranges. It also influences the evolution of emerging
      pathogens and the success of economically important crop species experimentally
      hybridized in search of strains with increased yields or disease resistance.
      Hybrid fitness may largely be determined by the pervasiveness of epistasis in the
      genome, as epistasis is known to debilitate hybrids through disrupted inter- and
      intragenic interactions. We identified two bacteriophages isolated from their
      natural environment, one the result of a past hybridization event involving an
      ancestor of the other phage and a third, unknown phage. By performing a
      reciprocal cross of the affected region of the genome, consisting of a single
      complete gene, we both approximately recreated and reversed this original
      hybridization event in two chimeric bacteriophage genomes. Subsequent adaptation
      of the hybrid phages allowed for the recovery of fitness losses incurred by the
      hybrid genotypes. Furthermore, adaptation led to the ascension of a substantially
      higher and previously inaccessible adaptive peak. We show that by allowing
      genotypes to take large leaps across the adaptive landscape rather than single
      mutational steps, hybridization can lead to huge long-term fitness gains in spite
      of short-term costs resulting from disrupted epistatic interactions,
      demonstrating that the success or failure of hybrids may be determined not by
      their initial fitness, but rather by their adaptive potential.

PMID- 24078089
TI  - The anti-tumor effect and increased tregs infiltration mediated by rAAV-SLC
      vector.
AB  - To explore the anti-tumor effect and immune mechanism mediated by a new
      recombinant adeno-associated virus (rAAV) encoding secondary lymphoid tissue
      chemokine (SLC) mature peptide gene. AAV Helper-Free system was used for rAAV-SLC
      package. The anti-tumor effect of SLC was detected by bearing tumor established
      from Hepal-6 cells both in C57BL/6J and nude mice. Flow cytometry analysis and
      IHC for Tumor-infiltrating T cells and CD11c+DCs were also investigated to
      explore the immunological mechanism. rAAV-SLC was successfully packaged in AAV293
      cells and transfected Hepal-6 tumor cells at high efficiency. The anti-tumor
      effect was demonstrated by less tumor weight and longer survival outcome.
      Coincident with the anti-tumor response, local elaboration of SLC within the
      tumor bed elicited a heavy infiltration of CD4+, CD8+T cells and CD11c+ dendritic
      cells into the tumor sites. More importantly, there was higher infiltration of
      Foxp3+ regulatory T cells (Tregs). Local elaboration of SLC mediated by rAAV-SLC
      has strong T cell mediated anti-tumor effect. The study also suggested that Tregs
      in the tumor microenvironment tampered the anti-tumor effect.

PMID- 24078091
TI  - Association between SNPs in microRNA-machinery genes and tuberculosis
      susceptibility in Chinese Tibetan population.
AB  - Tuberculosis (TB) is caused by infection with Mycobacterium tuberculosis and
      remains a leading cause of morbidity and mortality caused by infectious agents
      worldwide. Although our current understanding of the pathogenesis of TB is far
      from clear, there is a growing body of evidence suggesting a genetic contribution
      to the etiology of TB. By analyzing 294 TB cases and 287 healthy controls in a
      Chinese Tibetan population, we used a candidate gene approach to evaluate the
      association between six single nucleotide polymorphisms (rs10719, rs3757,
      rs3742330, rs636832, rs7813, and rs3744741) in microRNA machinery genes and TB
      susceptibility. The genotypic distributions of rs3757 and rs3744741 in controls
      were not in accordance with the Hardy-Weinberg Equilibrium (P < 0.05). Logistic
      regression analysis demonstrated that subjects carrying rs3742330 GG genotype had
      significantly decreased risk for TB than individuals carrying AA genotype [odds
      ratio (OR) = 0.31, 95 % confidence interval (CI) 0.12-0.75, P = 0.004. Carrying
      the G allele of rs3742330 was associated with a 27 % decreased risk for TB (95 %
      CI 0.55-0.97, P = 0.03). However, no significant associations were found for
      rs10719, rs636832 and rs7813. Computational modeling suggests that the rs3742330
      lies within a predicted binding site (seed region) for microRNA-632 (miR-632) and
      that the G allele alters the affinity of microRNA-mRNA binding by disrupting the
      local structure of dicer 1, ribonuclease type III (DICER) mRNA, presumably
      allowing for upregulated DICER expression. Taken together, our data suggest that
      common genetic variations DICER may influence TB risk, possibly through miR-632
      mediated regulation. Replication of our studies in other populations will
      strengthen our understanding of this association.

PMID- 24078092
TI  - Association between the receptor for advanced glycation end products gene
      polymorphisms and coronary artery disease.
AB  - Receptor for advanced glycation end products (RAGE) is a cell-surface molecule
      member of the immunoglobulin superfamily and thought to play a critical role in
      diabetic atherosclerosis. A growing body of studies has been conducted to
      determine the extent to which the variants of RAGE gene influence the risk of
      coronary artery disease (CAD). However, these have reported conflicting results.
      To investigate this inconsistency, we performed a comprehensive meta-analysis on
      the associations between the RAGE -374T/A, -429T/C, and Gly82Ser polymorphisms
      and the risk of CAD. A total of 4,402 cases and 6,081 controls from 17 published
      case-control studies were included. The overall odds ratio (OR) of CAD was 0.99
      (95 % CI 0.87-1.13), 1.06 (95 % CI 0.95-1.18) and 1.12 (95 % CI 0.90-1.39) for 
      374A, -429C, and the minor S allele of the Gly82Ser polymorphism, respectively.
      Similarly, no significant results were observed for these polymorphisms using
      dominant model. However, when stratified by diabetic/non-diabetic status of the
      CAD patients, we found significant association among Caucasian type two diabetic
      CAD patients with the -374A allele [OR 1.39, 95 % CI 1.10-1.76, P(Z) = 0.006],
      while no association was detected between the -374T/A polymorphism and non
      diabetic CAD in Caucasians [OR 0.79, 95 % CI 0.58-1.07, P(Z) = 0.13]. In
      conclusion, this meta-analysis suggested that possession of the -374A allele may
      be a risk factor in CAD among Caucasian patients with type two diabetes.

PMID- 24078093
TI  - Cytokine single nucleotide polymorphisms in patients' with gallstone: dose TGF
      beta gene variants affect gallstone formation?
AB  - Gallstone is a common biliary disorder with several risk factors. Immune
      responses and inflammatory cytokines are important in this disease; as a result,
      some cytokines can be detected in bile fluid. In this research, cytokine gene
      polymorphisms were studied, and their effects on gallstone formation were
      evaluated. On 158 gallstone patients and 254 normal subjects, by PCR- RFLP
      method, IL-4-C590T polymorphism and by ARMS-PCR method, IFN-gamma T+874A, TNF
      alpha-A308G, IL-6 G-174C and TGF-beta T+869C variants were studied. Pathologic
      evaluations were done on surgical specimens. There were no significant
      differences in distribution of evaluated polymorphisms between patient group and
      normal control group (P > 0.05), except TGF-beta +869T allele (P = 0.04, OR =
      1.23, 95 % CI = 1-1.79) which was higher in patients with gallstone. Although the
      pro-inflammatory cytokines such as TNF-alpha and IL-6 may promote gallstone
      formation, in this study no significant correlation between TNF-alpha and IL-6
      polymorphisms and gallstone formation was seen. It is taught that TGF-beta may
      affect gallbladder cells to promote gallstone formation and higher producer TGF
      beta +869T allele can be a risk factor of gallstone disease, so further studies
      would be more elucidative

PMID- 24078094
TI  - Association of CDKN1B gene polymorphisms with susceptibility to breast cancer: a
      meta-analysis.
AB  - A number of case-control studies have been conducted to investigate the
      association of CDKN1B gene polymorphisms with breast cancer. However, these
      studies reported conflicting results. The aim of our study was to quantitatively
      summarize the association of CDKN1B gene polymorphisms with breast cancer.
      Systemic searches of the PubMed, Excerpta Medica Database, and Chinese Biomedical
      Literature Database databases were performed, with the last report up to Oct
      2012. Odds ratios (ORs) with 95 % confidence intervals (CIs) were used to assess
      the strength of the association. Seven studies including 6,822 cases and 7,186
      controls were involved in this meta-analysis, which was performed for two CDKN1B
      gene polymorphisms (rs2066827 and rs34330). Significant association was found for
      rs34330 polymorphism (T versus C: OR = 1.10, 95 % CI = 1.03-1.18, P = 0.003; CT +
      TT versus CC: OR = 1.38, 95 % CI = 0.98-1.93, P = 0.07; TT versus CC + CT: OR =
      1.06, 95 % CI = 0.93-1.21, P = 0.38; TT versus CC: OR = 1.23, 95 % CI = 1.04
      1.45, P = 0.02; CT versus CC: OR = 1.42, 95 % CI = 0.97-2.09, P = 0.07), but not
      for rs2066827 polymorphism (G versus T: OR = 0.99, 95 % CI = 0.91-1.08, P = 0.84;
      TG + GG versus TT: OR = 0.98, 95 % CI = 0.89-1.08, P = 0.69; GG versus TT + TG:
      OR = 1.04, 95 % CI = 0.83-1.30, P = 0.75; GG versus TT: OR = 1.03, 95 % CI = 0.82
      1.30, P = 0.77; TG versus TT: OR = 0.97, 95 % CI = 0.88-1.08, P = 0.58). This
      meta-analysis suggests that breast cancer may be associated with CDKN1B gene
      rs34330 polymorphism, but not rs2066827 polymorphism.

PMID- 24078095
TI  - Circulating microparticles in patients with coronary heart disease and its
      correlation with interleukin-6 and C-reactive protein.
AB  - Microparticles (MPs) are vesicles released from activated or apoptotic cells. MP
      derive from various cells, most notably platelets, but also leucocytes,
      lymphocytes, erythrocytes, and endothelial cells. The aim of this study was to
      investigate endothelial MP (EMP), platelet MP (PMP), lymphocyte MP and monocyte
      MP and TF-positive MPs (TF+ MPs) in patients with coronary heart disease (CHD),
      and to evaluate the correlation of these MPs with Interleukin-6 (IL-6) and C
      reactive protein (CRP). Different cell-derived MPs and TF+ MPs were analyzed by
      flow cytometry in 40 patients with myocardial infarction (MI), 30 unstable angina
      (UA), 20 stable angina (SA) and 20 healthy individuals, and IL-6 and CRP were
      determined by ELISA and special protein analyzer, respectively. Compared with SA
      and control, EMP and PMP was significantly elevated in MI and UA (P < 0.001), and
      TF+ MPs was significantly elevated in MI and UA (P < 0.001). EMP and PMP
      correlated with IL-6 (r = 0.822, P < 0.001 and r = 0.567, P < 0.001;
      respectively) or CRP level (r = 0.597, P < 0.001 and r = 0.66, P < 0.001;
      respectively). Different cell-derived MPs in CHD may indicate the different
      pathophysiological changes in vessels, and MPs may both participate in the
      development of thrombosis and enhance the vascular inflammation.

PMID- 24078090
TI  - Molecular phylogeny and biogeography of lac insects (Hemiptera: Kerriidae)
      inferred from nuclear and mitochondrial gene sequences.
AB  - Lac insects are commercial scale insects with high economic value. The combined
      molecular phylogeny of 20 lac insect populations was generated using elongation
      factor 1 alpha, mitochondrial cytochrome c oxidase subunit I and the small
      subunit ribosomal RNA gene loci. The 20 populations of lac insects clustered into
      four distinct clades supported by high bootstrap values in maximum parsimony,
      maximum likelihood and Bayesian analyses. Clade A at the base of the dendrogram
      comprises Kerria ruralis and two populations of Kerria lacca and is the branch
      with most primitive species. Clade B includes K. lacca, Kerria sindica and the
      three populations P, V and Z from India. They clustered with high bootstrap
      support and have evolved later than those in Clade A. The three unidentified
      populations P, V and Z exhibited a close relationship with K. lacca and are the
      same species. In Clade C, three populations of Kerria yunnanensis (Ym, Yj and
      Yl), population Ys from Thailand and population H from India clustered as a
      group, in which population H clustered with Ym with 100 % bootstrap in all three
      analysis methods. In Clade D, Kerria chinensis, Kerria pusana and three
      populations of K. yunnanensis clustered together with strong support, and are
      located in the upper branches of the dendrogram and are recently evolved taxa.
      The majority of populations from the Indian subcontinent clade are more closely
      related to outgroup taxa from the primitive family Pseudococcidae, as compared to
      the Eurasian populations. Phylogenetic analysis reveals that the Indian
      subcontinent is the centre of original of lac insects which have translocated to
      the Eurasian Continent. Based on the theory of continental drift and existing
      fossil records, it is suggested that lac insect evolved from ancient scale
      insects during the late Cretaceous period when the Indian subcontinent drifted
      towards the Eurasian Continent. Changes in the global environment have impacted
      on the distribution and evolution of lac insects during the mid-Cretaceous and
      early Cenozoic. With increasing temperatures lac insects are likely to
      translocate to subtropical areas.

PMID- 24078096
TI  - Association of fibroblast growth factor (FGF-21) as a biomarker with primary
      mitochondrial disorders, but not with secondary mitochondrial disorders
      (Friedreich Ataxia).
AB  - Mitochondrial respiratory chain deficiencies are a group of more than 100
      disorders of adults and children, with highly variable phenotypes. The high
      prevalence of mitochondrial disorders (MIDs) urges the clinician to diagnose
      these disorders accurately, which is difficult in the light of highly variable
      and overlapping phenotypes, transmission patterns and molecular backgrounds.
      Fibroblast growth factor 21 (FGF-21) is an important endocrine and paracrine
      regulator of metabolic homeostasis. The FGF-21 transcript is reported to be
      abundantly expressed in liver, but little is known about the regulation of FGF-21
      expression in other tissues. FGF-21 could play a role in the metabolic
      alterations that are often associated with mitochondrial diseases. The aim of
      this study was to show the association of the FGF-21 biomarker with human primary
      MIDs and secondary MIDs in suspected patients in Iran. Serum FGF-21 levels were
      determined using ELISA in 47 mitochondrial patients, including 32 with primary
      MIDs, 15 patients with Friedreich ataxia as a secondary MID and 30 control
      subjects. Serum FGF-21 levels were significantly higher in subjects with the
      primary MIDs (p < 0.05), compared to subjects without MIDs. However, serum FGF-21
      levels did not show significant increase in subjects with FA as a secondary MID.
      There is an association between increasing concentrations of FGF-21 with
      mitochondrial diseases, suggesting FGF-21 as a biomarker for diagnosis of primary
      MIDs in humans. However, this biomarker is not appropriate for the diagnosis of
      FA.

PMID- 24078097
TI  - Regulation and function of Arabidopsis AtGALK2 gene in abscisic acid response
      signaling.
AB  - AtGALK2 belongs to galactokinase of GHMP family in Arabidopsis thaliana. Two
      homozygous T-DNA insertion mutants (Atgalk2-1 and Atgalk2-2) of the AtGALK2 gene
      were identified. The AtGALK2 gene was highly expressed in flowers and roots, but
      less in stems, leaves and petioles. It was found that the expression of AtGALK2
      gene was induced by NaCl and ABA. The two Atgalk2 mutants showed higher
      germination activity when treated with ABA and NaCl than wild type (Col-0).
      Through comparing the results of seed germination, root growth, stomatal
      aperture, water loss, and proline accumulation between the Atgalk2 mutants and
      Col-0, it was found that Atgalk2 mutants showed less sensitive to ABA than Col-0.
      The expression levels of ABI1, ABI2, RAB18, ABF3, RD22, RD29A, and RD29B in the
      Atgalk2 mutants were higher than in Col-0. However, the expression level of OST1
      in the Atgalk2 mutants was lower than in Col-0. Taken together, these results
      suggested AtGALK2 was required for abscisic acid regulation of seed germination,
      root growth and gene expression, and was involved in salt and osmotic stress
      response in the early development stage. This study provides important clues to
      galactokinase activities of GHMP family in ABA signaling and plant development.

PMID- 24078098
TI  - Molecular characterization of two small heat shock protein genes in rice: their
      expression patterns, localizations, networks, and heterogeneous overexpressions.
AB  - Heat stress is an example of a severe abiotic stress that plants can suffer in
      the field, causing a significant detrimental effect on their growth and
      productivity. Understanding the mechanism of plant response to heat stress is
      important for improving the productivity of crop plants under global warming. We
      used a microarray dataset that is deposited in the public database to evaluate
      plant responses to heat stress, and we selected the top 10 genes that are highly
      expressed under heat stress in rice. Two genes, OsSHSP1 (Os03g16030) and OsSHSP2
      (Os01g04380), were selected for further study. These genes were highly induced in
      response to salt and drought but not in response to cold. In addition, OsSHSP1
      and OsSHSP2 gene transcripts were induced under abscisic acid and salicylic acid
      but not under jasmonic acid and ethylene. Subcellular localization of proteins of
      35S::OsSHSP1 were associated with the cytosol, whereas those of and 35S::OsSHSP2
      were associated with the cytosol and nucleus. Heterogeneous overexpression of
      both genes exhibited higher germination rates than those of wild-type plants
      under the salt treatment, but not under heat or drought stress, supporting a
      hypothesis regarding functional specialization of members of small heat-shock
      protein family over evolutionary time. The network of both genes harboring nine
      sHSPs as well as at least 13 other chaperone genes might support the idea of a
      role for sHSPs in the chaperone network. Our findings might provide clues to shed
      light on the molecular functions of OsSHSP1 and OsSHSP2 in response to abiotic
      stresses, especially heat stress.

PMID- 24078100
TI  - Endobronchial ultrasound-guided transbronchial biopsy and brushing: a comparative
      evaluation for the diagnosis of peripheral pulmonary lesions.
AB  - OBJECTIVES: The diagnosis of peripheral pulmonary lesions (PPLs) often involves
      endobronchial ultrasound (EBUS)-guided transbronchial biopsy (TBB), washing and
      brushing. Certain echoic features of PPL have been associated with biopsy yield.
      This study compared yields of TBB and bronchial washing (TBBW) with those of TBBW
      plus bronchial brushing and analysed the associations between clinical and echoic
      features and yield. METHODS: We performed a retrospective review of 271 patients
      undergoing TBB for PPL. TBBW was performed in 139 patients and 132 underwent TBBW
      plus brushing. RESULTS: The diagnostic yield of TBBW plus brushing was superior
      to that of TBBW (80.3 vs 66.2%, P < 0.01). In TBBW patients, lesions <3 cm (57.1
      vs 73.7%, P < 0.05), EBUS probe adjacent to the lesion (47.6 vs 74.2%, P < 0.01),
      continuous margin (56.5 vs 75.7%, P < 0.01) and homogeneous echogenicity (51.0 vs
      75.0%, P < 0.01) predicted lower yields, but adding bronchial brushing rendered
      the diagnostic yields similar, irrespective of EBUS echoic features, leaving
      lesion size of <3 cm (odds ratio 2.81; 95% confidence interval 1.08-7.31, P <
      0.05) as the single independent predictor of lower yield by multivariate
      regression analysis. TBB plus brushing was not inferior to TBBW plus brushing
      (78.8 vs 80.3%, P = 0.88). CONCLUSIONS: Bronchial brushing boosted diagnostic
      yields, particularly for PPLs with echoic features previously associated with a
      reduced biopsy yield.

PMID- 24078099
TI  - Enhanced cognitive control near the hands.
AB  - Recent research has shown that objects near the hands receive preferential visual
      processing. However, it is not known whether proximity to the hands can affect
      executive functions. Here we show, using two popular paradigms, that people
      exhibit enhanced cognitive control for stimuli that are near their hands: We
      observed reduced interference from incongruent flankers in a visual attention
      task, and reduced costs when switching to an alternative task in a task-switching
      paradigm. The results reveal a remarkable influence of posture on cognitive
      function and have implications for assessing the potential benefits of working on
      handheld devices.

PMID- 24078101
TI  - Computed tomography manifestations of a malignant solitary fibrous tumour of the
      pleura with distinct blood supply from celiac trunk.
AB  - Solitary fibrous tumours of the pleura (SFTPs) are rare and roughly 80% of them
      have a benign course. Malignant SFTPs are seldom reported, as are their computed
      tomography (CT) manifestations. We report the case of a 45-year old male patient
      who presented with coughing for over 2 months. A large lesion in his right
      hemithorax was found by chest X-ray. CT scan showed patchy areas and a sharp time
      attenuation curve. CT angiography reconstruction revealed a distinct feeding
      vessel from celiac trunk. After surgery, the tumour was confirmed to be a
      malignant SFTP by immunochemistry. 

PMID- 24078102
TI  - Significance and function of different spinal collateral compartments following
      thoracic aortic surgery: immediate versus long-term flow compensation.
AB  - Iatrogenic paraplegia has been accompanying cardiovascular surgery since its
      beginning. As a result, surgeons have been developing many theories about the
      exact mechanisms of this devastating complication. Thus, the impact of single
      arteries that contribute to the spinal perfusion is one of the most discussed
      subjects in modern surgery. The subsequent decision of reattachment or the
      permanent disconnection of these intercostal arteries divides the surgical
      community. On the one hand, the anatomical or vascular approach pleads for the
      immediate reimplantation to reconstruct the anatomical situation. On the other
      hand, the decision of the permanent disconnection aims at avoiding stealing
      phenomenon away from the spinal vascular network. This spinal collateral network
      can be described as consisting of three components-the intraspinal and two
      paraspinal compartments-that feed the nutrient arteries of the spinal cord. The
      exact functional impact of the different compartments of the collateral network
      remains poorly understood. In this review, the function of the intraspinal
      compartment in the context of collateral network principle as an immediate
      emergency backup system is described. The exact structure and architectural
      principles of the intraspinal compartment are described. The critical parameters
      with regard to the risk of postoperative spinal cord ischaemia are the number of
      anterior radiculomedullary arteries (ARMAs) and the distance between them in
      relation to the longitudinal extent of aortic disease. The paraspinal network as
      a sleeping reserve is proposed as the long-term backup system. This sleeping
      reserve has to be activated by arteriogenic stimuli. These are presented briefly,
      and prior findings regarding arteriogenesis are discussed in the light of the
      collateral network concept. Finally, the role of preoperative visualization of
      the ARMAs in order to evaluate the risk of postoperative paraplegia is
      emphasized. 

PMID- 24078103
TI  - Granuloma in ANCA-associated vasculitides: another reason to distinguish between
      syndromes?
AB  - The 2012 renewed Chapel Hill Consensus Conference (CHCC) officially named three
      clinicopathological entities, i.e. granulomatosis with polyangiitis (GPA),
      eosinophilic granulomatosis with polyangiitis (EGPA), and microscopic
      polyangiitis (MPA), as major variants of anti-neutrophil cytoplasmic antibody
      (ANCA)-associated vasculitides (AAV). Recent genetic and cohort studies revealed
      the need for further differentiation between the entities, for example regarding
      differences in outcome. As well as ANCA reactivity, upper and lower airway
      disease were found to be differentiating factors for AAV variants, improving
      prognostic ability regarding relapse prediction and associated clinical features.
      Extravascular granulomatosis, or "granuloma", which describes both clinically
      relevant granulomatous manifestations and histopathologically documented
      granulomatous inflammation, is characteristic of localized and systemic GPA, but
      not MPA. This review summarizes new knowledge regarding granuloma in the head and
      neck region of AAV, its histomorphological equivalents in the upper and lower
      respiratory tract, and evidence for a granulomatous phenotype of a persistent
      localized GPA variant. This comprises the development of disease activity and
      damage scores for extravascular lesions in the ear, nose, and throat (ENT)
      regions, and imaging techniques. In addition, findings linking extravascular
      manifestations to granulomatous inflammation are described. We hypothesize that,
      as for ANCA, necrotizing granulomatous inflammation and its clinical
      manifestations are discriminators, assisting subclassification of AAV and/or GPA
      subphenotypes which will be useful both for designing clinical trials and for
      treating patients successfully. 

PMID- 24078104
TI  - Updated review of complementary and alternative medicine treatments for systemic
      lupus erythematosus.
AB  - It is estimated that over 50 % of patients with systemic lupus erythematosus
      (SLE) have utilized complementary and alternative medicine (CAM) treatments to
      reduce symptoms and manage their health. However, there are relatively few
      randomized controlled trials of CAM for SLE. This review describes recent studies
      of vitamins and supplements, acupuncture, and mind-body interventions in SLE
      patients. The recent trials of CAM treatments for SLE indicate that supplements
      such as vitamin D, omega 3 fatty acids, N-acetyl cysteine and turmeric show some
      promise for reducing SLE disease activity. In addition, mind-body methods such as
      cognitive-behavioral therapy and other counseling interventions may improve mood
      and quality of life in SLE. 

PMID- 24078105
TI  - Innovations in diagnostic imaging of localized prostate cancer.
AB  - PURPOSE: In recent years, various imaging modalities have been developed to
      improve diagnosis, staging, and localization of early-stage prostate cancer
      (PCa). METHODS: A MEDLINE literature search of the time frame between 01/2007 and
      06/2013 was performed on imaging of localized PCa. RESULTS: Conventional
      transrectal ultrasound (TRUS) is mainly used to guide prostate biopsy. Contrast
      enhanced ultrasound is based on the assumption that PCa tissue is
      hypervascularized and might be better identified after intravenous injection of a
      microbubble contrast agent. However, results on its additional value for cancer
      detection are controversial. Computer-based analysis of the transrectal
      ultrasound signal (C-TRUS) appears to detect cancer in a high rate of patients
      with previous biopsies. Real-time elastography seems to have higher sensitivity,
      specificity, and positive predictive value than conventional TRUS. However, the
      method still awaits prospective validation. The same is true for prostate
      histoscanning, an ultrasound-based method for tissue characterization. Currently,
      multiparametric MRI provides improved tissue visualization of the prostate, which
      may be helpful in the diagnosis and targeting of prostate lesions. However, most
      published series are small and suffer from variations in indication, methodology,
      quality, interpretation, and reporting. CONCLUSIONS: Among ultrasound-based
      techniques, real-time elastography and C-TRUS seem the most promising techniques.
      Multiparametric MRI appears to have advantages over conventional T2-weighted MRI
      in the detection of PCa. Despite these promising results, currently, no
      recommendation for the routine use of these novel imaging techniques can be made.
      Prospective studies defining the value of various imaging modalities are urgently
      needed.

PMID- 24078106
TI  - Existential neuroscience: effects of mortality salience on the neurocognitive
      processing of attractive opposite-sex faces.
AB  - Being reminded of the inherently finite nature of human existence has been
      demonstrated to elicit strivings for sexual reproduction and the formation and
      maintenance of intimate relationships. Recently, it has been proposed that the
      perception of potential mating partners is influenced by mortality salience.
      Using functional magnetic resonance imaging, we investigated the neurocognitive
      processing of attractive opposite-sex faces after priming with death-related
      words for heterosexual men and women. Significant modulations of behavioral and
      neural responses were found when participants were requested to decide whether
      they would like to meet the presented person. Men were more in favor of meeting
      attractive women after being primed with death-related words compared to a no
      prime condition. Increased neural activation could be found under mortality
      salience in the left anterior insula and the adjacent lateral prefrontal cortex
      (lPFC) for both men and women. As previously suggested, we believe that the lPFC
      activation reflects an approach-motivated defense mechanism to overcome concerns
      that are induced by being reminded of death and dying. Our results provide
      insight on a neurocognitive level that approach motivation in general, and mating
      motivation in particular is modulated by mortality salience. 

PMID- 24078107
TI  - Opioid receptor blockade and warmth-liking: effects on interpersonal trust and
      frontal asymmetry.
AB  - The emotion 'warmth-liking' (WL) associated with feelings of affection and
      acceptance is regularly activated in social contexts. WL has been suggested to be
      more closely related to the consummatory phase of post-goal attainment positive
      affect than to pre-goal attainment positive affect/approach motivation and to be
      partly mediated by brain opioids. To validate these assumptions we employed
      film/imagery to induce either a neutral emotional state or WL in female
      participants after intake of either placebo or the opioid antagonist naltrexone.
      Dependent variables were emotion self-report, interpersonal trust (TRUST, i.e. a
      behavioral indicator of WL) and frontal asymmetry (i.e. an electroencephalogram
      (EEG) indicator of approach motivation/behavioral activation). We found that
      participants reported more WL in the placebo/WL group than in the placebo/neutral
      group and both naltrexone groups. In addition, TRUST increased in the WL group
      after placebo, but not after naltrexone, and this pattern was reversed in the
      neutral control groups. Consequently, opioid blockade suppressed or even reversed
      the effects of the WL induction on the levels of self-report and behavior,
      respectively. In addition, we observed reduced relative left-frontal asymmetry in
      the WL (vs neutral) group, consistent with reduced approach motivation. Overall,
      these results suggest opioidergic influences on WL and TRUST and reduced approach
      motivation/behavioral activation for the positive emotion WL.

PMID- 24078108
TI  - Drosera peltata Smith var. lunata (Buch.-Ham.) C. B. Clarke as a feasible source
      of plumbagin: phytochemical analysis and antifungal activity assay.
AB  - Drosera peltata Smith var. lunata (Buch.-Ham.) C. B. Clarke (DPVL) fractions and
      plumbagin were tested via broth microdilution techniques on Rhizopus oryzae,
      Aspergillus flavus, Aspergillus niger, Aspergillus oryzae, Penicillium citrinum.
      All of the test substances [petroleum ether, chloroform, ethyl acetate, n-butanol
      fraction and aqueous residue (AR)] except for the AR were active against all the
      tested strains. The petroleum ether fraction (PEF) was the most active (MIC =
      5.86-46.88 MUg/ml, MFC = 23.44-93.75 MUg/ml) of the five tested substances and
      therefore, was selected for further analysis. Based on antifungal activity,
      bioactivity-guided fractionation of the PEF led to the isolation of plumbagin.
      The structure of plumbagin was elucidated by 1H and 13C NMR. Using HPLC, DPVL was
      found to be a new source of plumbagin. Reversed-phase HPLC was performed using a
      mobile phase of water and methanol, and peaks were detected at 254 nm. Plumbagin
      showed a good linear relationship at concentrations ranging from 0.625 to 10
      MUg/ml. Both the intraday and the interday precision showed that the method was
      precise, with RSDs of at least 3% at different concentrations. Recovery rates
      ranging from 97.86 to 99.94% were observed, which indicate that the method is
      accurate. The specificity of the method was established by checking the peak
      purity of plumbagin. For six independent measurements, the average plumbagin
      content in DPVL was 11.05 +/- 0.31 mg/g of dried material. The validated HPLC
      method provides a new basis for assessing DPVL quality.

PMID- 24078109
TI  - A rapid knockdown effect of Penicillium citrinum for control of the mosquito
      Culex quinquefasciatus in Thailand.
AB  - Twenty local isolates of entomopathogenic fungi were determined for control of
      the larvae and adults of Culex quinquefasciatus. In a laboratory experiment, a
      Penicillium sp. CM-010 caused 100% mortality of third-instar larvae within 2 h
      using a conidial suspension of 1 * 106 conidia ml-1. Its LC50 was 3 * 105 conidia
      ml-1, and the lethal time (LT50) was 1.06 h. Cloning and sequencing of its
      internal transcribed spacer region indicated that this Penicillium species is
      Penicillium citrinum (100% identity in 434 bp). Mortality of the adult was
      highest with Aspergillus flavus CM-011 followed with Metarhizium anisopliae CKM
      048 from 1 * 109 conidia ml-1. P. citrinum CM-010 at 1 * 106 conidia ml-1 killed
      100% larvae within 2 h while Bacillus thuringiensis var. israelensis at 5 ITU ml
      1 required 24 h. This P. citrinum CM-010 also greatly reduced survival of C.
      quinquefasciatus larvae in an unreplicated field test. Light and transmission
      electron micrographs showed that the fungal conidia were ingested by the larvae
      and deposited in the gut. The metabolite patulin was produced by P. citrinum CM
      010 instead of citrinin.

PMID- 24078110
TI  - Direct production of feruloyl oligosaccharides and hemicellulase inducement and
      distribution in a newly isolated Aureobasidium pullulans strain.
AB  - Studies were carried out to screen and identify strains that are able to directly
      produce ferulic oligosaccharides (FOs) from wheat bran (WB). The inducement and
      distribution of hemicellulases from strain 2012, which was identified as a non
      melanin secreting strain of Aureobasidium pullulans (A. pullulans), were also
      determined. In a 60 g/L WB solution, A. pullulans could produce 545 nmol/L FOs,
      64.12 IU/mL xylanase and 0.14 IU/mL ferulic acid esterase (FAE). A. pullulans was
      cultivated in media with WB, glucose, xylose, sucrose, lactose or xylan as the
      carbon source, and hemicellulases were mainly induced by xylan and WB and
      inhibited by glucose and sucrose. Xylanase and FAE were mainly present in the
      culture filtrate, xylosidase in the hyphal filaments and arabinofuranosidase was
      a membrane-bound enzyme. The yield of FOs was positively correlated to the
      hemicellulases activity, and significantly positively (P < 0.05) correlated to
      the xylanase activity (r = 0.992).

PMID- 24078111
TI  - Method for RNA extraction and cDNA library construction from microbes in crop
      rhizosphere soil.
AB  - Techniques to analyze the transcriptome of the soil rhizosphere are essential to
      reveal the interactions and communications between plants and microorganisms in
      the soil ecosystem. In this study, different volumes of Al2(SO4)3 were added to
      rhizosphere soil samples to precipitate humic substances, which interfere with
      most procedures of RNA and DNA analyses. After humic substances were
      precipitated, cells of soil microorganisms were broken by vortexing with glass
      beads, and then DNA and RNA were recovered using Tris-HCl buffer with LiCl, SDS,
      and EDTA. The crude extract was precipitated and dissolved in RNAse-free water,
      and then separated by agarose gel electrophoresis. We determined the optimum
      volume of Al2(SO4)3 for treating rhizosphere soil of rice, tobacco, sugarcane,
      Rehmannia glutinosa, and Pseudostellaria heterophylla. The crude nucleic acids
      extract from rice soil was treated with DNase I and then RNA was purified using a
      gel filtration column. The purified RNA was reverse-transcribed into single
      strand cDNA and then ligated with an adaptor at each end before amplifying ds
      cDNA. The ds cDNA was sub-cloned for subsequent gene sequence analysis. We
      conducted qPCR to amplify 16S ribosomal DNA and observed highly efficient
      amplification. These results show that the extraction method can be optimized to
      isolate and obtain high-quality nucleic acids from microbes in different
      rhizosphere soils, suitable for genomic and post-genomic analyses.

PMID- 24078112
TI  - MU-Synthesis of dissimilation process of glycerol to 1,3-propanediol in microbial
      continuous culture.
AB  - In this paper, robust control problem using MU-synthesis in microbial continuous
      culture is studied. The dissimilation process of glycerol to 1,3-propanediol
      cannot avoid the disturbances caused by uncertain factors. Based on the
      biodynamical model, a control system with the initial glycerol concentration as
      input control is proposed to simplify the controller design. MU-synthesis method
      is applied to find a feedback controller to assure both of robust stability and
      robust performance of the closed-loop system simultaneously. To solve the
      corresponding structured singular value optimization problem, a converged result
      is obtained through D-K iteration method. The MU-synthesis system is also
      compared with the corresponding H(infinity) system. The simulation results
      indicate that the MU-controller might be more feasible for the continuous
      bioprocess controlling.

PMID- 24078114
TI  - Craniotomy vs. craniectomy for posterior fossa tumors: a prospective study to
      evaluate complications after surgery.
AB  - BACKGROUND: Posterior fossa surgery traditionally implies permanent bone removal.
      Although suboccipital craniectomy offers an excellent exposure, it could lead to
      complications. Thus, some authors proposed craniotomy as a valuable alternative
      to craniectomy. In the present study we compare postoperative complications after
      craniotomy or craniectomy for posterior fossa surgery. METHODS: We prospectively
      collected data for a consecutive series of patients who underwent either
      posterior fossa craniotomy or craniectomy for tumor resection. We divided
      patients into two groups based on the surgical procedure performed and safety,
      complication rates and length of hospitalization were analyzed. Craniotomies were
      performed with Control-Depth-Attachment((r)) drill and chisel, while we did
      craniectomies with perforator and rongeurs. RESULTS: One-hundred-fifty-two
      patients were included in the study (craniotomy n =100, craniectomy n =52). We
      detected no dural damage after bone removal in both groups. The total
      complication rate related to the technique itself was 7 % for the craniotomy
      group and 32.6 % for the craniectomy group (<0.0001). Pseudomeningocele occurred
      in 4 % vs. 19.2 % (p =0.0009), CSF leak in 2 % vs. 11.5 % (p =0.006) and wound
      infection in 1 % vs. 1.9 % (p =0.33), respectively. Post-operative hydrocephalus,
      a multi-factorial complication which could affect our results, was also
      calculated and occurred in 4 % of the craniotomy vs. 9.6 % of the craniectomy
      group (p =0.08). The mean length of in-hospital stay was 9.3 days for the
      craniotomy group and 11.8 days for the craniectomy group (p =0.10). CONCLUSIONS:
      The present study suggests that fashioning a suboccipital craniotomy is as
      effective and safe as performing a craniectomy; both procedures showed similar
      results in preserving dural integrity, while post-operative complications were
      fewer when a suboccipital craniotomy was performed.

PMID- 24078113
TI  - Molecular diversity of the ammonia-oxidizing bacteria community in disused tin
      mining ponds located within Kampar, Perak, Malaysia.
AB  - Disused tin-mining ponds make up a significant amount of water bodies in Malaysia
      particularly at the Kinta Valley in the state of Perak where tin-mining
      activities were the most extensive, and these abundantly available water sources
      are widely used in the field of aquaculture and agriculture. However, the natural
      ecology and physicochemical conditions of these ponds, many of which have been
      altered due to secondary post-mining activities, remains to be explored. As
      ammonia-oxidizing bacteria (AOB) are directly related to the nutrient cycles of
      aquatic environments and are useful bioindicators of environmental variations,
      the focus of this study was to identify AOBs associated with disused tin-mining
      ponds that have a history of different secondary activities in comparison to
      ponds which were left untouched and remained as part of the landscape. The 16S
      rDNA gene was used to detect AOBs in the sediment and water sampled from the
      three types of disused mining ponds, namely ponds without secondary activity,
      ponds that were used for lotus cultivation and post-aquaculture ponds. When the
      varying pond types were compared with the sequence and phylogenetic analysis of
      the AOB clone libraries, both Nitrosomonas and Nitrosospira-like AOB were
      detected though Nitrosospira spp. was seen to be the most ubiquitous AOB as it
      was present in all ponds types. However, AOBs were not detected in the sediments
      of idle ponds. Based on rarefaction analysis and diversity indices, the disused
      mining pond with lotus culture indicated the highest richness of AOBs. Canonical
      correspondence analysis indicated that among the physicochemical properties of
      the pond sites, TAN and nitrite were shown to be the main factors that influenced
      the community structure of AOBs in these disused tin-mining ponds.

PMID- 24078115
TI  - Spinal magnetic resonance imaging with reduced specific absorption rate in
      patients harbouring a spinal cord stimulation device - A single-centre
      prospective study analysing safety, tolerability and image quality.
AB  - BACKGROUND: Spinal cord stimulation (SCS) is an accepted treatment in patients
      with failed back surgery (FBS), complex regional pain syndrome (CRPS) and
      persistent radicular pain following surgery. In order to avoid patient hazards or
      device malfunction manufacturers advise to abstain from magnetic resonance
      imaging (MRI) in patients with implanted electrodes or pulse generators. METHODS:
      In a prospective study, 13 patients harbouring an implanted Medtronic Spinal Cord
      Stimulation (SCS) device underwent MRI (1.5 T) of the lumbar (n=13), the cervical
      (n=2) or the thoracic spine (n=1) following the development of new spinal
      symptoms. An adapted MRI protocol was used limiting the transmitted energy and
      specific absorption rate. Tolerability and safety were assessed by means of a
      standardized patient evaluation form documenting pain on a visual analogue scale
      (0-10), neurologic deficit, and discomfort during the scan. In addition, overall
      satisfaction with the examination procedure was rated on a Likert scale (1-5).
      Image quality was rated independently and blinded to the presence of a SCS device
      by the radiologist and the surgeon as equivalent, superior or inferior compared
      to the standard spine MRI examination. RESULTS: None of the 13 patients
      investigated by the modified spinal MRI protocol experienced new neurological
      deficits, worsening of symptoms or a defect/malfunction of the implant device.
      Three patients (23.1 %) reported transient warm sensation in the location of the
      electrode and in one case intermittent slight tingling in the lower extremities.
      Overall satisfaction with the examination was 1.13 +/- 0.34 according to Likert
      scale (1-5). The image quality was rated - not statistically significant -
      slightly inferior to standard lumbar spine imaging (0.82 +/- 0.54) with a kappa
      value of 0.68 between the two investigators. MRI examinations detected relevant
      and new lesions in 9 (69.2 %) patients which affected treatment in 8 (61.5 %)
      individuals. CONCLUSION: Using a protocol with a reduced specific energy
      absorption rate, spinal MRI examinations in patients with SCS can be considered
      safe. The current view that neurostimulators are a general contraindication to MR
      examinations has to be reconsidered in patients with new or progressive spinal
      symptoms.

PMID- 24078117
TI  - Effects of low-intensity pulsed ultrasound on cell viability, proliferation and
      neural differentiation of induced pluripotent stem cells-derived neural crest
      stem cells.
AB  - Low-intensity pulsed ultrasound (LIPUS) acting on induced pluripotent stem cells
      derived neural crest stem cells (iPSCs-NCSCs) is considered a promising therapy
      to improve the efficacy of injured peripheral nerve regeneration. Effects of
      LIPUS on cell viability, proliferation and neural differentiation of iPSCs-NCSCs
      were examined respectively in this study. LIPUS at 500 mW cm(-2) enhanced the
      viability and proliferation of iPSCs-NCSCs after 2 days and, after 4 days, up
      regulated gene and protein expressions of NF-M, Tuj1, S100beta and GFAP in iPSCs
      NCSCs whereas after 7 days expression of only NF-M, S100beta and GFAP were up
      regulated. LIPUS treatment at an appropriate intensity can, therefore, be an
      efficient and cost-effective method to enhance cell viability, proliferation and
      neural differentiation of iPSCs-NCSCs in vitro for peripheral nerve tissue
      engineering.

PMID- 24078116
TI  - Bcl-2 family in inter-organelle modulation of calcium signaling; roles in
      bioenergetics and cell survival.
AB  - Bcl-2 family proteins, known for their apoptosis functioning at the mitochondria,
      have been shown to localize to other cellular compartments to mediate calcium
      (Ca2+) signals. Since the proper supply of Ca2+ in cells serves as an important
      mechanism for cellular survival and bioenergetics, we propose an integrating role
      for Bcl-2 family proteins in modulating Ca2+ signaling. The endoplasmic reticulum
      (ER) is the main Ca2+ storage for the cell and Bcl-2 family proteins
      competitively regulate its Ca2+ concentration. Bcl-2 family proteins also
      regulate the flux of Ca2+ from the ER by physically interacting with inositol
      1,4,5-trisphosphate receptors (IP3Rs) to mediate their opening. Type 1 IP3Rs
      reside at the bulk ER to coordinate cytosolic Ca2+ signals, while type 3 IP3Rs
      reside at mitochondria-associated ER membrane (MAM) to facilitate mitochondrial
      Ca2+ uptake. In healthy cells, mitochondrial Ca2+ drives pyruvate into the citric
      acid (TCA) cycle to facilitate ATP production, while a continuous accumulation of
      Ca2+ can trigger the release of cytochrome c, thus initiating apoptosis. Since
      multiple organelles and Bcl-2 family proteins are involved in Ca2+ signaling, we
      aim to clarify the role that Bcl-2 family proteins play in facilitating Ca2+
      signaling and how mitochondrial Ca2+ is relevant in both bioenergetics and
      apoptosis. We also explore how these insights could be useful in controlling
      bioenergetics in apoptosis-resistant cell lines.

PMID- 24078118
TI  - Glycosylation analysis of recombinant neutral protease I from Aspergillus oryzae
      expressed in Pichia pastoris.
AB  - Neutral protease I from Aspergillus oryzae 3.042 was expressed in Pichia pastoris
      and its N-glycosylation properties were analyzed. After purification by nickel
      affinity chromatography column, the recombinant neutral protease (rNPI) was
      confirmed to be N-glycosylated by periodicacid/Schiff's base staining and Endo H
      digestion. Moreover, the deglycosylated protein's molecular weight decreased to
      43.3 kDa from 54.5 kDa analyzed by SDS-PAGE and MALDI-TOF-MS, and the
      hyperglycosylation extent was 21 %. The N-glycosylation site of rNPI was analyzed
      by nano LC-MS/MS after digesting by trypsin and Glu-C, and the unique potential
      site Asn41 of mature peptide was found to be glycosylated. Homology modeling of
      the 3D structure of rNPI indicated that the attached N-glycans hardly affected
      neutral protease's activity due to the great distance away from the active site
      of the enzyme.

PMID- 24078119
TI  - Plant-derived mAbs have effective anti-cancer activities by increasing
      ganglioside expression in colon cancers.
AB  - An epithelial cell adhesion molecule (EpCAM) was selectively expressed in human
      colorectal carcinoma. Treatment with plant-derived anti-EpCAM mAb (mAbP CO17-1A)
      and RAW264.7 cells inhibited cell growth in the human colorectal cancer cell line
      SW620. In SW620 treated with mAbP CO17-1A and RAW264.7 cells, expression of p53
      and p21 increased, whereas the expression of G1 phase-related proteins, cyclin
      D1, CDK4, cyclin E, and CDK2, decreased, similar to mammalian-derived mAb (mAbM)
      CO17-1A. Similar to mAbM CO17-1A, treatment with mAbP CO17-1A and RAW264.7 cell
      decreased the expression of anti-apoptotic protein, Bcl-2, but the expression of
      pro-apoptotic proteins Bax, TNF-alpha, caspase-3, caspase-6, caspase-8 and
      caspase-9, increased. Cells treated with mAbP CO17-1A and RAW264.7 cells
      expressed metastasis-related gangliosides, GM1 and GD1a, similar to mAbM CO17-1A.
      These results suggest that mAbP CO17-1A is as effective on anti-cancer activity
      as mAbM CO17-1A.

PMID- 24078120
TI  - Stabilization of human immunodeficiency virus type 1 reverse transcriptase by
      site-directed mutagenesis.
AB  - Human immunodeficiency virus type 1 (HIV-1) reverse transcriptase (RT) is a
      heterodimer containing 66 kDa p66 and 51 kDa p51 subunits. We previously showed
      that HIV-1 group M (HIV-1 M) RT and HIV-1 group O (HIV-1 O) RT have higher
      affinities for dTTP and template-primer (T/P) than Moloney murine leukemia virus
      RT, which is currently used for cDNA synthesis, suggesting that they might also
      be useful for cDNA synthesis (Konishi et al. Appl Biochem Biotechnol 2013, 169:77
      87). Here, we have increased the thermostability of both HIV-1 M RT and HIV-1 O
      RT by site-directed mutagenesis. The Asp443 -> Ala mutation, which abolishes
      RNase H activity, was introduced into the p66 subunits of HIV-1 M RT and HIV-1 O
      RT. The temperatures that reduced the initial activity by 50 % of the resulting
      mutants, HIV-1 M p66D443A/p51 and HIV-1 O p66D443A/p51, were 44 and 52  degrees
      C, respectively, which were higher than those of wild-type HIV-1 M p66/p51 (42 
      degrees C) and HIV-1 O p66/p51 (48  degrees C). The highest temperature at which
      both HIV-1 M p66D443A/p51 and HIV-1 O p66D443A/p51 exhibited cDNA synthesis
      activity was 68  degrees C, which was higher than for the wild-type enzymes (62
      and 66  degrees C, respectively).

PMID- 24078121
TI  - Gene cloning and soluble expression of Aspergillus niger phytase in E. coli
      cytosol via chaperone co-expression.
AB  - A phytase gene from Aspergillus niger was isolated and two Escherichia coli
      expression systems, based on T7 RNA polymerase promoter and tac promoter, were
      used for its recombinant expression. Co-expression of molecular chaperone,
      GroES/EL, aided functional cytosolic expression of the phytase in E. coli BL21
      (DE3). Untagged and maltose-binding protein-tagged recombinant phytase showed an
      activity band of ~49 and 92 kDa, respectively, on a zymogram. Heterologously
      expressed phytase was fractionated from endogenous E. coli phytase by (NH4)2SO4
      precipitation. The enzyme had optimum activity at 50  degrees C and pH 6.5.

PMID- 24078122
TI  - Decolorization of Alizarin Red and other synthetic dyes by a recombinant laccase
      from Pichia pastoris.
AB  - A cDNA encoding for a laccase was isolated from the white-rot fungus Lenzites
      gibbosa by RT-PCR and expressed in the Pichia pastoris. The laccase native signal
      peptide efficiently directed the secretion of the recombinant laccase in an
      active form. Factors influencing laccase expression, such as pH, cultivation
      temperature, copper concentration and methanol concentration, were optimized. The
      recombinant enzyme was purified to electrophoretic homogeneity, and was estimated
      to have a MW of ~61.5 kDa. The purified enzyme behaved similarly to the native
      laccase produced by L. gibbosa and efficiently decolorized Alizarin Red, Neutral
      Red, Congo Red and Crystal Violet, without the addition of redox mediators. The
      decolorization capacity of this recombinant enzyme suggests that it could be a
      useful biocatalyst for the treatment of dye-containing effluents. This study is
      the first report on the synthetic dye decolorization by a recombinant L. gibbosa
      laccase.

PMID- 24078123
TI  - Development of a low-cost, phyto-tunnel system using Portulaca grandiflora and
      its application for the treatment of dye-containing wastewaters.
AB  - A phyto-tunnel was developed using a drilled PVC pipe. It was planted with
      Portulaca grandiflora and used for the treatment of a textile effluent and a dye
      mixture. COD, BOD, TOC, conductivity, turbidity, total suspended solids and total
      dissolved solids of the textile effluent, and dye mixture were decreased by 57,
      45, 43, 52, 76, 77 and 24 % within 96 h, and 49, 62, 41, 63, 58, 71 and 33 %,
      within 60 h, respectively, after treatment. The effluent and dye mixture were
      decolorized up to 87 and 90 % within 96 and 60 h, respectively. Significant
      induction in activities of lignin peroxidase, tyrosinase and DCIP reductase was
      observed in root tissues of the plants. FTIR, HPLC and HPTLC of untreated and
      treated samples showed the formation of new metabolites and preferential dye
      removal. Phytotoxicity studies revealed the non-toxic nature of the metabolites.

PMID- 24078124
TI  - Optimization of gamma-amino butyric acid production in a newly isolated
      Lactobacillus brevis.
AB  - An isolate from kimchi, identified as Lactobacillus brevis, accumulated gamma
      aminobutyric acid (GABA), a major inhibitory neurotransmitter, in the culture
      medium. Optimal culture conditions for growth of L. brevis and production of GABA
      were 6 % (w/v) l-glutamic acid, 4 % (w/v) maltose, 2 % (w/v) yeast extract, 1 %
      (w/v) NaCl, 1 % (w/v) CaCl2, 2 g Tween 80/l, and 0.02 mM pyridoxal 5'-phosphate
      at initial pH 5.25 and 37  degrees C. GABA reached 44.4 g/l after 72 h
      cultivation with a conversion rate 99.7 %, based on the amount (6 %) of l
      glutamic acid added. GABA was purified using ion exchange column chromatography
      with 70 % recovery and 97 % purity.

PMID- 24078125
TI  - Finding elementary flux modes in metabolic networks based on flux balance
      analysis and flux coupling analysis: application to the analysis of Escherichia
      coli metabolism.
AB  - Elementary modes (EMs) are steady-state metabolic flux vectors with minimal set
      of active reactions. Each EM corresponds to a metabolic pathway. Therefore,
      studying EMs is helpful for analyzing the production of biotechnologically
      important metabolites. However, memory requirements for computing EMs may hamper
      their applicability as, in most genome-scale metabolic models, no EM can be
      computed due to running out of memory. In this study, we present a method for
      computing randomly sampled EMs. In this approach, a network reduction algorithm
      is used for EM computation, which is based on flux balance-based methods. We show
      that this approach can be used to recover the EMs in the medium- and genome-scale
      metabolic network models, while the EMs are sampled in an unbiased way. The
      applicability of such results is shown by computing "estimated" control-effective
      flux values in Escherichia coli metabolic network.

PMID- 24078126
TI  - Production of ginsenosides Rg1 and Rh1 by hydrolyzing the outer glycoside at the
      C-6 position in protopanaxatriol-type ginsenosides using beta-glucosidase from
      Pyrococcus furiosus.
AB  - The specific activity of a recombinant beta-glucosidase from Pyrococcus furiosus
      for protopanaxatriol (PPT)-type ginsenosides followed the order Rf > R1 > Re > R2
      > Rg2, which were converted to Rh1, Rg1, Rg1, Rh1, and Rh1, respectively. No
      activity was observed with Rg1 and Rh1. Thus, P. furiosus beta-glucosidase
      hydrolyzed the outer glycoside at the C-6 position in PPT-type ginsenosides
      whereas the enzyme did not hydrolyze the inner glucoside at the C-6 position and
      the glucoside at the C-20 position. The activity for Rf was optimal at 95 
      degrees C, pH 5.5, 5 mM ginsenoside, and 32 U enzyme l-1. Under these conditions,
      P. furiosus beta-glucosidase completely converted from R1 to Rg1 after 10 h, with
      a productivity of 0.4 g l-1 h-1 and completely converted Rf to Rh1 after 1.2 h,
      with a productivity of 2.74 g l-1 h-1.

PMID- 24078127
TI  - Nutrient limitation in Auxenochlorella protothecoides induces qualitative changes
      of fatty acid and expression of caleosin as a membrane protein associated with
      oil bodies.
AB  - Oil bodies formed in Auxenochlorella protothecoides induced during limited
      nutrition had a coating of caleosin. The total lipid content obtained from A.
      protothecoides in unstressed cultures (first week) was ~210 mg/g compared to the
      231 mg/g obtained in the third week (nutrient limited) and 290 mg/g obtained in
      the fourth week (nutrient limited). The proportion of total saturated fatty acids
      increased from 28 to 46 %, whereas that of total polyunsaturated fatty acids
      decreased from 52 to 35 %. The expression levels of the 28 kDa caleosin protein
      in A. protothecoides rose to a maximum up to 4 weeks; immunolocalization studies
      showed that caleosin was predominantly associated with the membranes of oil
      bodies.

PMID- 24078128
TI  - Production of 2-butanol from crude glycerol by a genetically-engineered
      Klebsiella pneumoniae strain.
AB  - Klebsiella pneumoniae was engineered to produce 2-butanol from crude glycerol as
      a sole carbon source by expressing acetolactate synthase (ilvIH), keto-acid
      reducto-isomerase (ilvC) and dihydroxy-acid dehydratase (ilvD) from K.
      pneumoniae, and alpha-ketoisovalerate decarboxylase (kivd) and alcohol
      dehydrogenase (adhA) from Lactococcus lactis. Engineered K. pneumonia, ?ldhA/pBR
      iBO (ilvIH-ilvC-ilvD-kivd-adhA), produced 2-butanol (160 mg l-1) from crude
      glycerol. To increase the yield of 2-butanol, we eliminated the 2,3-butanediol
      pathway from the recombinant strain by inactivating alpha-acetolactate
      decarboxylase (adc). This further engineering step improved the yield of 2
      butanol from 160 to 320 mg l-1. This represents the first successful attempt to
      produce 2-butanol from crude glycerol.

PMID- 24078129
TI  - Impact of heparin-binding domain of recombinant human osteocalcin-fibronectinIII9
      14 on the osteoblastic cell response.
AB  - Fibronectin (FN) containing a heparin-binding domain (HBD) and an Arg-Gly-Asp
      (RGD) domain can promote cell adhesion and proliferation compared to FN that
      contained only RGD. Here, we have engineered recombinant human osteocalcin (rhOC)
      with FN type III9-14 (rhOC-FNIII9-14) containing RGD and HBD to promote the
      cellular activity of MC3T3-E1 cells, including adhesion, proliferation, and
      differentiation. RhOC-FNIII9-14 significantly increased cell adhesion and
      proliferation of MC3T3-E1 cells compared to rhOC-FNIII9-10 (P < 0.05). Moreover,
      rhOC-FNIII9-14 showed osteogenic differentiation of MC3T3-E1 cells in
      mineralization activity and osteogenic gene expression.

PMID- 24078130
TI  - Production and secretion of a heterologous protein by turnip hairy roots with
      superiority over tobacco hairy roots.
AB  - A fully contained and efficient heterologous protein production system was
      designed using Brassica rapa rapa (turnip) hairy roots. Two expression cassettes
      containing a cauliflower mosaic virus (CaMV) 35S promoter with a duplicated
      enhancer region, an Arabidopsis thaliana sequence encoding a signal peptide and
      the CaMV polyadenylation signal were constructed. One cassette was used to
      express the green fluorescent protein (GFP)-encoding gene in hairy roots grown in
      flasks. A stable and fast-growing hairy root line secreted GFP at >120 mg/l
      culture medium. GFP represented 60 % of the total soluble proteins in the culture
      medium. Turnip hairy roots retained sustainable growth and stable GFP production
      over 3 years. These results were superior to those obtained using tobacco hairy
      roots.

PMID- 24078131
TI  - Identification and functional characterization of polyunsaturated fatty acid
      elongase (McELOVL5) gene from pike eel (Muraenesox cinereus).
AB  - The cDNA coding for a polyunsaturated fatty acid elongase (McELOVL5) was isolated
      from the brain of the pike eel (Muraenesox cinereus) being based on available
      sequences in 23 types of fish. Four sequence variants were identified with
      different amino acid substitutions as compared with two clones of McELOVL5 gene
      (McELOVL5 11.7 and McELOVL5 12.4). When the two variants of McELOVL5 were
      expressed in Saccharomyces cerevisiae, the two recombinant yeasts elongated gamma
      linolenic acid (GLA, 18:3n-6) to di-homo-gamma-linolenic acid (DGLA, 20:3n-6) but
      differed in the rate of GLA conversion to DGLA. Cells transformed with McELOVL5
      12.4 also converted arachidonic acid (20:4n-6) and eicosapentaenoic acid (20:5n
      3) to docosatetraenoic acid (22:4n-6) and docosapentaenoic acid (22:5n-3),
      respectively. However McELOVL5 11.7 lost its function for the elongation of C20
      fatty acids. The four sequence variants have changed substrate specificities.
      Three-dimensional models of the McELOVL5 proteins are suggested.

PMID- 24078132
TI  - Permeabilized probiotic Lactobacillus plantarum as a source of beta-galactosidase
      for the synthesis of prebiotic galactooligosaccharides.
AB  - Permeabilized probiotic Lactobacillus plantarum was used as a source of beta
      galactosidase for the synthesis of galactooligosaccharides (GOS) from lactose.
      beta-galactosidase activity was highest when galactose (1,724 Miller Units) was
      used as a carbon source compared to lactose, sucrose or glucose at 37  degrees C,
      18 h. Permeabilized cells had the highest transgalactosylation activity resulting
      in 34 % (w/w) GOS synthesis from 40 % (w/v) lactose at 50  degrees C over 12 h.
      HPLC revealed that the GOS were composed of 13 % disaccharides (non-lactose), 17
      % trisaccharides and 4 % tetrasaccharides that were further confirmed by ESI-MS.

PMID- 24078133
TI  - Cloning, expression, and characterization of coenzyme-B12-dependent diol
      dehydratase from Lactobacillus diolivorans.
AB  - The three gldCDE genes from Lactobacillus diolivorans, that encode the three
      subunits of the glycerol dehydratase, were cloned and the proteins were co
      expressed in soluble form in Escherichia coli with added sorbitol and betaine
      hydrochloride. The purified enzyme exists as a heterohexamer (alpha2beta2gamma2)
      structure with a native molecular mass of 210 kDa. It requires coenzyme B12 for
      catalytic activity and is subject to suicide inactivation by glycerol during
      catalysis. The enzyme had maximum activity at pH 8.6 and 37  degrees C. The
      apparent K m values for coenzyme B12, 1,2-ethanediol, 1,2-propanediol, and
      glycerol were 1.5 MUM, 10.5 mM, 1.3 mM, and 5.8 mM, respectively. Together, these
      results indicated that the three genes gldCDE encoding the proteins make up a
      coenzyme B12-dependent diol dehydratase and not a glycerol dehydratase.

PMID- 24078134
TI  - RNA interference-mediated repression of SmCPS (copalyldiphosphate synthase)
      expression in hairy roots of Salvia miltiorrhiza causes a decrease of tanshinones
      and sheds light on the functional role of SmCPS.
AB  - Tanshinones are a group of bioactive abietane-type norditerpenoid quinone
      compounds in Salvia miltiorrhiza. Copalyldiphosphate synthase of S. miltiorrhiza
      (SmCPS) is the first key enzyme in tanshinone biosynthesis from the universal
      diterpene precursor geranylgeranyl diphosphate. Hairy roots of S. miltiorrhiza
      were transformed with Agrobacterium rhizogenes carrying an RNA interference
      (RNAi) construct designed to silence SmCPS, and we examined the resulting SmCPS
      expression and tanshinone accumulation. In SmCPS-RNAi hairy roots, the transcript
      level of SmCPS was reduced to 26 % while the dihydrotanshinone I and
      cryptotanshinone levels were decreased by 53 and 38 % compared to those of the
      vector control hairy roots; tanshinone IIA was not detected. Therefore, the
      decreased expression of SmCPS caused a decrease in tanshinone levels which
      verifies that SmCPS is a key enzyme for tanshinone biosynthesis in S.
      miltiorrhiza.

PMID- 24078135
TI  - The potential of novel biomarkers to improve risk prediction of type 2 diabetes.
AB  - The incidence of type 2 diabetes can be reduced substantially by implementing
      preventive measures in high-risk individuals, but this requires prior knowledge
      of disease risk in the individual. Various diabetes risk models have been
      designed, and these have all included a similar combination of factors, such as
      age, sex, obesity, hypertension, lifestyle factors, family history of diabetes
      and metabolic traits. The accuracy of prediction models is often assessed by the
      area under the receiver operating characteristic curve (AROC) as a measure of
      discrimination, but AROCs should be complemented by measures of calibration and
      reclassification to estimate the incremental value of novel biomarkers. This
      review discusses the potential of novel biomarkers to improve model accuracy. The
      range of molecules that serve as potential predictors of type 2 diabetes includes
      genetic variants, RNA transcripts, peptides and proteins, lipids and small
      metabolites. Some of these biomarkers lead to a statistically significant
      increase of model accuracy, but their incremental value currently seems too small
      for routine clinical use. However, only a fraction of potentially relevant
      biomarkers have been assessed with regard to their predictive value. Moreover,
      serial measurements of biomarkers may help determine individual risk. In
      conclusion, current risk models provide valuable tools of risk estimation, but
      perform suboptimally in the prediction of individual diabetes risk. Novel
      biomarkers still fail to have a clinically applicable impact. However, more
      efficient use of biomarker data and technological advances in their measurement
      in clinical settings may allow the development of more accurate predictive models
      in the future.

PMID- 24078136
TI  - Aggravation of diabetic nephropathy in BCL-2 interacting cell death suppressor
      (BIS)-haploinsufficient mice together with impaired induction of superoxide
      dismutase (SOD) activity.
AB  - AIMS/HYPOTHESIS: B cell CLL/lymphoma 2 (BCL-2)-interacting cell death suppressor
      (BIS), known as an anti-stress and anti-apoptotic protein, has been reported to
      modulate susceptibility to oxidative stress. This study investigated the
      potential role of BIS as an antioxidant protein in diabetic nephropathy. METHODS:
      Diabetes was induced in BIS-heterozygote (BIS-HT) mice via streptozotocin
      injections and the resulting phenotypes were compared with those of BIS-wild-type
      (BIS-WT) mice over the 20 weeks following diabetes induction. RESULTS: Renal
      injuries, represented by increased plasma creatinine levels and increased
      albuminuria, were greater in diabetic BIS-HT mice than in diabetic BIS-WT mice,
      and were accompanied by a significant increase in reactive oxygen species (ROS)
      and oxidative stress markers. Moreover, renal pathological changes and the
      apoptotic process were accelerated in diabetic BIS-HT mice compared with diabetic
      BIS-WT mice with the same degree of hyperglycaemia; all were restored by 4
      hydroxy-2,2,6,6-tetramethylpiperidine-N-oxyl (tempol) treatment. The levels of
      NADPH oxidase and related proteins were not significantly higher in diabetic BIS
      HT mice compared with diabetic BIS-WT mice. However, levels of superoxide
      dismutase (SOD)1 and SOD2 increased on the induction of diabetes in BIS-WT mice
      but not in BIS-HT mice, correlating with the total SOD activity. An in vitro
      study showed that knockdown of BIS production also resulted in impaired induction
      of SOD activity as well as SOD levels in HK-2 and NMS cells, concomitant with
      significant ROS accumulation. CONCLUSION/INTERPRETATION: Our results suggest that
      the decreased antioxidant capacity of BIS aggravates diabetic nephropathy in
      diabetic BIS-HT mice, possibly as a result of the disruption in the regulation of
      SOD protein quality under oxidative stress.

PMID- 24078137
TI  - Retinal proteome alterations in a mouse model of type 2 diabetes.
AB  - AIMS/HYPOTHESIS: Diabetic retinopathy is a major complication of type 2 diabetes
      and the leading cause of blindness in adults of working age. Neuronal defects are
      known to occur early in disease, but the source of this dysfunction is unknown.
      The aim of this study was to examine differences in the retinal membrane proteome
      among non-diabetic mice and mouse models of diabetes either with or without
      metformin treatment. METHODS: Alterations in the retinal membrane proteome of 10
      week-old diabetic db/db mice, diabetic db/db mice orally treated with the anti
      hyperglycaemic metformin, and congenic wild-type littermates were examined using
      label-free mass spectrometry. Pathway enrichment analysis was completed with
      Genomatix and Ingenuity. Alterations in Slc17a7 mRNA and vesicular glutamate
      transporter 1 (VGLUT1) protein expression were evaluated using real-time
      quantitative PCR and IMMUNOFLUORESCENCE. RESULTS: A total of 98 proteins were
      significantly differentially abundant between db/db and wild-type animals.
      Pathway enrichment analysis indicated decreases in levels of proteins related to
      synaptic transmission and cell signalling. Metformin treatment produced 63
      differentially abundant proteins compared with untreated db/db mice, of which
      only 43 proteins were found to occur in both datasets, suggesting that treatment
      only partially normalises the alterations induced by diabetes. VGLUT1, which is
      responsible for loading glutamate into synaptic vesicles, was found to be
      differentially abundant in db/db mice and was not normalised by metformin. The
      decrease in Slc17a7/VGLUT1 was confirmed by transcriptomic and immunocytochemical
      analysis. CONCLUSIONS/INTERPRETATION: These findings expand the knowledge of the
      protein changes in diabetic retinopathy and suggest that membrane-associated
      signalling proteins are susceptible to changes that are partially ameliorated by
      treatment

PMID- 24078138
TI  - The state of the art of endothermal ablation.
AB  - Complaints relating to reflux in the venous system can be addressed by
      conservative, surgical, or interventional treatment options. The aim of the
      treatment is to prevent complications and progression of venous disease and to
      improve patients' quality of life. Endovenous thermal ablation therapies have
      become the most frequently used type of therapy for saphenous varicose veins. The
      available endovenous thermal techniques are endovenous laser ablation,
      radiofrequency ablation, and endovenous steam ablation. In this review, the
      procedures, indications, and treatment parameters of the three endovenous thermal
      ablation treatments are discussed as well as their advantages and disadvantages.

PMID- 24078139
TI  - The factors affecting success rate of emergency intubation.

PMID- 24078140
TI  - The factors affecting success rate of emergency intubation:  author's reply.

PMID- 24078141
TI  - Biological endpoints, enzyme activities, and blood cell parameters in two anuran
      tadpole species in rice agroecosystems of mid-eastern Argentina.
AB  - Different biological variables of tadpoles, including survival, development and
      growth rates, and biomarkers [cholinesterases, glutathione-S-transferases (GST),
      and blood cell morphology] were evaluated in two anuran species, Scinax
      squalirostris (Hylidae) and Leptodactylus mystacinus (Leptodactylidae), using in
      situ experimental chambers in a rice field (RF) sprayed with insecticide Lambda
      cyhalothrin (LTC) by aircraft in Santa Fe Province, Argentina. We found a
      significant decrease in body weight (0.62 +/- 0.04 g) of L. mystacinus and an
      increased development rate of S. squalirostris in individuals from RF (41 +/- 1;
      Gosner) with respect to individuals from the reference site (RS: 0.93 +/- 0.04 g
      and 37 +/- 0; respectively). In S. squalirostris, individuals from RF mean values
      of butyrylcholinesterase activities decreased at 48 (4.09 +/- 0.32 nmol min-1 mg
      1 of TP) and 96 h (3.74 +/- 0.20 nmol min-1 mg-1 of TP), whereas inhibition of
      acetylcholinesterase was observed at 96 h (47.44 +/- 2.78 nmol min-1 mg-1 of TP).
      In L. mystacinus from RF, an induction of acetylcholinesterase activity was
      observed at 96 h (36.01 +/- 1.09 nmol min-1 mg-1 of TP). Glutathione-S
      transferase levels varied between species, being higher in L. mystacinus
      individuals but lower in S. squalirostris from RF at 48 (272.29 +/-11.78 and
      71.87 +/- 1.70 nmol min-1 mg-1 of TP; respectively) and 96 h (279.25 +/- 13.06
      and 57.62 +/- 4.58 nmol min-1 mg-1 of TP, respectively). Blood cell parameters
      revealed a lower number of mitotic cells (MC: 0.36 +/- 0.31%o for S.
      squalirostris and 0.08 +/- 0.05 %o for L. mystacinus) and higher number of
      eosinophils (E: 3.45 +/- 1.75 %o for S. squalirostris and 7.64 +/- 0.98 %o for L.
      mystacinus) in individuals from the RF than in individuals from the RS (MC: 2.55
      +/- 0.74 %o for S. squalirostris and 1.87 +/- 0.72%o for L. mystacinus; and E:
      0.13 +/- 0.09 for S. squalirostris and 3.20 +/- 0.80 for L. mystacinus). Overall,
      our results demonstrate the existence of apparent differences in sensitivity
      between species in a series of sublethal responses to short-term exposure in RF
      after the application of Lambda-cyhalothrin. We suggest that the integral use of
      biological endpoints (development and growth) together with biomarkers
      (cholinesterase, GST, and blood cell parameters) may be a promising integral
      procedure for investigating pesticide exposure in wild frog populations.

PMID- 24078142
TI  - Determinants of diarrhea prevalence in urban slums: a comparative assessment
      towards enhanced environmental management.
AB  - This study relies on a comparative assessment of diarrhea occurrence in two urban
      slums to identify salient factors influencing case prevalence. Primary data were
      collected from both areas using a structured closed-ended questionnaire coupled
      with bottled and public water quality sampling and analysis at households
      reporting diarrhea cases. The water quality analysis showed contamination at the
      household level due primarily to the location of water storage tanks, as well as
      in some brands of bottled water due to lack of enforcement of source monitoring.
      Descriptive statistics and chi-square distribution tests revealed significant
      difference in diarrhea cases in both study areas which was correlated with the
      educational level of household head, financial status, type of water storage
      tank, and corresponding cleaning frequency as well as the adoption of measures to
      treat water or the use of bottled water.

PMID- 24078143
TI  - Spatial distribution and risk assessment of heavy metals in sediments from a
      hypertrophic plateau lake Dianchi, China.
AB  - The sediment in Dianchi Lake, a hypereutrophic plateau lake in southwest China,
      was investigated and the concentration of heavy metals (Cu, Cr, Ni, Zn, Pb, Fe,
      Mn, and Cd) in the sediment and sediment properties were determined. Their
      spatial distribution and sources were analyzed using multivariate statistics. The
      result indicated that the studied metals exhibited three distinct spatial
      patterns; that is, Cu, Pb, Zn, and Ni had a similar distribution, with a
      concentration gradient from the north to the south part of the lake; Cd and Cr
      presented a similar distribution; Fe and Mn presented a quite different
      distribution than other metals, which indicated their different sources and
      geochemistry processes. Correlation and cluster analysis (CA) provided origin
      information on these metals and the CA result was observed corresponding to those
      three spatial patterns. Principal component analysis further displayed metal
      source and driving factors; that is, Cu, Pb, Zn, Ni, Cd, and Cr were mainly
      derived from anthropogenic sources, and Fe and Mn were mainly the result of
      natural processes. Sediment assessment was conducted using geoaccumulation index
      (Igeo), potential ecological risk indices, and USEPA guidelines. The result
      indicated that, generally, Cd was the most serious risk metal; Pb and Cu posed
      moderate potential ecological risk; Cr, Zn, and Ni had slight ecological risk; Fe
      and Mn had little risk. Comparison of the assessment tools showed that each of
      the methods had its limitation and could bias the result, and the combined use of
      the methodologies and local knowledge on lithology or metal background value of
      soil in the practice would give a more comprehensive understanding of the metal
      risk or pollution. Statistical analysis also indicated that nutrients had
      different impacts on Fe, Mn, and trace elements, which implied that in the
      assessment of metal risk, nutrients impact should be taken into consideration
      especially for eutrophic waters.

PMID- 24078144
TI  - Biological monitoring and health effects of low-level exposure to N-methyl-2
      pyrrolidone: a cross-sectional study.
AB  - PURPOSE: To examine the value of urinary 5-hydroxy-N-methyl-2-pyrrolidone (5
      HNMP) and 2-hydroxy-N-methylsuccinimide (2-HMSI) in a population of workers
      exposed to N-methyl-2-pyrrolidone (NMP) and to look for health effects of
      exposure to this organic solvent. METHODS: Airborne NMP was determined according
      to the NIOSH method. Urinary 5-HNMP and 2-HMSI (after and before next shift) were
      determined by liquid chromatography with tandem mass spectrometry. Outcomes were
      effects on lung, kidney, skin and mucous membranes, nervous system,
      haematopoiesis and liver determined by clinical examination and laboratory
      measurements. Univariate statistical methods and multiple regressions were used
      to analyse results. Skin resorption, smoking and other potential confounders were
      taken into account. RESULTS: Three hundred twenty-seven workers were eligible out
      of which 207 workers (63%) participated. Ninety-one of these worked with NMP.
      Occupational exposure to NMP did often not occur daily and ranged from non
      detectable to 25.8 mg/m3 (median = 0.18). Urinary 2-HMSI (mg/l; before next
      shift) was the best biomarker of exposure to NMP, explaining about 70% of the
      variance, but most likelihood ratios did not allow for ruling exposure in or out,
      at these low levels of exposure. Creatinine adjustment did not improve the
      results clearly. No clear and consistent health effects could be associated with
      NMP exposure. No indication for a bias due to non-participation was found.
      CONCLUSIONS: Biological monitoring, primarily urinary 2-HMSI (mg/l; before next
      shift), is of value to estimate exposure to NMP even when exposure is irregular
      and low. Likelihood ratios of urinary 5-HMNP or 2-HMSI are, however, not quite
      satisfactory at these low levels. No irritant or other health effects were found.

PMID- 24078145
TI  - Toxicokinetic study of pyrrole adducts and its potential application for
      biological monitoring of 2,5-hexanedione subacute exposure.
AB  - PURPOSE: The formation of pyrrole adducts might be responsible for peripheral
      nerve injury caused by n-hexane, but there is not an effective biomarker for
      monitoring occupational exposure of n-hexane. The current study was designed to
      investigate the changes of pyrrole adducts in serum and urine of rats exposed to
      2,5-hexanedione (2,5-HD) and analyze the correlation between pyrrole adducts and
      2,5-HD. METHODS: Two groups of male Wistar rats (n = 8) were administered a
      single dose of 200 and 400 mg/kg 2,5-HD (i.p.), and another two groups (n = 8)
      were given daily dose of 200 and 400 mg/kg 2,5-HD (i.p.) for 5 days. Pyrrole
      adducts and 2,5-HD in serum and urine were determined, at different time points
      after dosing, using Ehrlich's reagent and gas chromatography, respectively.
      RESULTS: The levels of pyrrole adducts in serum accumulated in a time-dependant
      manner after repeated exposure to 2,5-HD, while pyrrole adducts in urine, and 2,5
      HD in serum and urine were kept stable. The half-life times (t1/2) of 2,5-HD and
      pyrrole adducts in serum were 2.27 +/- 0.28 and 25.3 +/- 3.34 h, respectively.
      Furthermore, the levels of pyrrole adducts in urine were significantly correlated
      with the levels of 2,5-HD in serum (r = 0.736, P < 0.001) and urine (r = 0.730, P
      < 0.001), and the levels of pyrrole adducts in serum were correlated with the
      cumulative dosage of 2,5-HD (r = 0.965, P < 0.001). CONCLUSION: The results
      suggested that pyrrole adducts in serum and urine might be markers of chronic
      exposure to n-hexane or 2,5-HD.

PMID- 24078146
TI  - Gas hold-up and oxygen mass transfer in three pneumatic bioreactors operating
      with sugarcane bagasse suspensions.
AB  - Sugarcane bagasse is a low-cost and abundant by-product generated by the
      bioethanol industry, and is a potential substrate for cellulolytic enzyme
      production. The aim of this work was to evaluate the effects of air flow rate
      (QAIR), solids loading (%S), sugarcane bagasse type, and particle size on the gas
      hold-up (epsilonG) and volumetric oxygen transfer coefficient (kLa) in three
      different pneumatic bioreactors, using response surface methodology. Concentric
      tube airlift (CTA), split-cylinder airlift (SCA), and bubble column (BC)
      bioreactor types were tested. QAIR and %S affected oxygen mass transfer
      positively and negatively, respectively, while sugarcane bagasse type and
      particle size (within the range studied) did not influence kLa. Using large
      particles of untreated sugarcane bagasse, the loop-type bioreactors (CTA and SCA)
      exhibited higher mass transfer, compared to the BC reactor. At higher %S, SCA
      presented a higher kLa value (0.0448 s-1) than CTA, and the best operational
      conditions in terms of oxygen mass transfer were achieved for %S < 10.0 g L-1 and
      QAIR > 27.0 L min-1. These results demonstrated that pneumatic bioreactors can
      provide elevated oxygen transfer in the presence of vegetal biomass, making them
      an excellent option for use in three-phase systems for cellulolytic enzyme
      production by filamentous fungi.

PMID- 24078147
TI  - Effect of bioconversion conditions on vanillin production by Amycolatopsis sp.
      ATCC 39116 through an analysis of competing by-product formation.
AB  - This study investigated the effects of transformation conditions such as initial
      pH, the initial concentration of glucose and yeast extract in the medium, and the
      separate addition of ferulic acid and vanillic acid, on the production of
      vanillin through an analysis of competing by-product formation by Amycolatopsis
      sp. ATCC 39116. The extent and nature of by-product formation and vanillin yield
      were affected by initial pH and different initial concentrations of glucose and
      yeast extract in the medium, with a high yield of vanillin and high cell density
      obtained at pH 8.0, 10 g/l glucose, and 8 g/l yeast extract. High concentrations
      of ferulic acid were found to negatively affect cell density. Additional
      supplementation of 100 mg/l vanillic acid, a metabolically linked by-product, was
      found to result in a high concentration of vanillin and guaiacol, an intermediate
      of vanillin. Via an analysis of the effect of these transformation conditions on
      competing by-product formation, high concentrations of ferulic acid were
      transformed with a molar yield to vanillin of 96.1 and 95.2 %, by Amycolatopsis
      sp. ATCC 39116 and Streptomyces V1, respectively, together with a minor
      accumulation of by-products. These are among the highest performance values
      reported in the literature to date for Streptomyces in batch cultures.

PMID- 24078148
TI  - Biohydrogen production from CO-rich syngas via a locally isolated
      Rhodopseudomonas palustris PT.
AB  - Biohydrogen production through water-gas shift (WGS) reaction by a biocatalyst
      was conducted in batch fermentation. The isolated photosynthetic bacterium
      Rhodopseudomonas palustris PT was able to utilize carbon monoxide and
      simultaneously produce hydrogen. Light exposure was provided as an indispensable
      requirement for the first stage of bacterial growth, but throughout the hydrogen
      production stage, the energy requirement was met through the WGS reaction. At
      ambient pressure and temperature, the effect of various sodium acetate
      concentrations in presence of CO-rich syngas on cell growth, carbon monoxide
      consumption, and biohydrogen production was also investigated. Maximal efficiency
      of hydrogen production in response to carbon monoxide consumption was recorded at
      86 % and the highest concentration of hydrogen at 33.5 mmol/l was achieved with
      sodium acetate concentration of 1.5 g/l. The obtained results proved that the
      local isolate; R. palustris PT, was able to utilize CO-rich syngas and generate
      biohydrogen via WGS reaction.

PMID- 24078149
TI  - Microscale methods to rapidly evaluate bioprocess options for increasing
      bioconversion yields: application to the omega-transaminase synthesis of chiral
      amines.
AB  - This work aims to establish microscale methods to rapidly explore bioprocess
      options that might be used to enhance bioconversion reaction yields: either by
      shifting unfavourable reaction equilibria or by overcoming substrate and/or
      product inhibition. As a typical and industrially relevant example of the
      problems faced we have examined the asymmetric synthesis of (2S,3R)-2-amino-1,3,4
      butanetriol from l-erythrulose using the omega-transaminase from Chromobacterium
      violaceum DSM30191 (CV2025 omega-TAm) and methylbenzylamine as the amino donor.
      The first process option involves the use of alternative amino donors. The second
      couples the CV2025 omega-TAm with alcohol dehydrogenase and glucose dehydrogenase
      for removal of the acetophenone (AP) by-product by in situ conversion to (R)-1
      phenylethanol. The final approaches involve physical in-situ product removal
      methods. Reduced pressure conditions, attained using a 96-well vacuum manifold
      were used to selectively increase evaporation of the volatile AP while polymeric
      resins were also utilised for selective adsorption of AP from the bioconversion
      medium. For the particular reaction studied here the most promising bioprocess
      options were use of an alternative amino donor, such as isopropylamine, which
      enabled a 2.8-fold increase in reaction yield, or use of a second enzyme system
      which achieved a 3.3-fold increase in yield.

PMID- 24078150
TI  - Up-regulation of tripartite motif-containing 29 promotes cancer cell
      proliferation and predicts poor survival in colorectal cancer.
AB  - Tripartite motif-containing 29 (TRIM29), also known as ataxia-telangiectasia
      group D, is structurally a member of the tripartite motif family of proteins,
      which characterized by the conserved RING finger, B-box, and coiled-coil domains.
      TRIM29 functions as an oncogene or a tumor suppressor depending on the tumor
      types. In this study, we aim to evaluate whether TRIM29 affects the tumorigenesis
      and progression of colorectal cancer. The expression of TRIM29 was investigated
      using real-time PCR in 40 pairs of colorectal cancer tissues and
      immunohistochemistry on a tissue microarray containing 203 cases of primary
      colorectal cancer paired with non-cancerous tissues. Down-regulation of TRIM29
      was achieved by transient transfection in RKO cell lines, and the effects of
      TRIM29 on tumor proliferation were evaluated by MTT and plate colony formation
      assays. Results indicated that TRIM29 expression was much higher in colorectal
      cancer tissues and significantly associated with the depth of tumor invasion,
      lymph node metastasis, distant metastasis, histological differentiation, vascular
      invasion, ki-67 index, and advanced tumor stage. Patients with TRIM29-positive
      tumors had a higher recurrence rate and poorer survival than patients with TRIM29
      negative tumors. In multivariate analyses, the TRIM29 expression was an
      independent factor for determining colorectal cancer prognosis after surgery.
      Moreover, down-regulation of TRIM29 inhibited tumor cell proliferation in vitro.
      In conclusion, TRIM29 plays an important role in promoting colorectal cancer
      progression. Our findings suggest that TRIM29 may serve as a novel biomarker for
      tumor recurrence and survival for colorectal cancer patients. 

PMID- 24078151
TI  - The paradox of dual roles in the RNA world: resolving the conflict between stable
      folding and templating ability.
AB  - The hypothesized dual roles of RNA as both information carrier and biocatalyst
      during the earliest stages of life require a combination of features: good
      templating ability (for replication) and stable folding (for ribozymes). However,
      this poses the following paradox: well-folded sequences are poor templates for
      copying, but poorly folded sequences are unlikely to be good ribozymes. Here, we
      describe a strategy to overcome this dilemma through G:U wobble pairing in RNA.
      Unlike Watson-Crick base pairs, wobble pairs contribute highly to the energetic
      stability of the folded structure of their sequence, but only slightly, if at
      all, to the stability of the folded reverse complement. Sequences in the RNA
      World might thereby combine stable folding of the ribozyme with an unstructured,
      reverse-complementary genome, resulting in a "division of labor" between the
      strands. We demonstrate this strategy using computational simulations of RNA
      folding and an experimental model of early replication, nonenzymatic template
      directed RNA primer extension. Additional study is needed to solve other problems
      associated with a complete replication cycle, including separation of strands
      after copying. Interestingly, viroid RNA sequences, which have been suggested to
      be relics of an RNA World (Diener, Proc Natl Acad Sci USA 86:9370-9374, 1989),
      also show significant asymmetry in folding energy between the infectious (+) and
      template (-) strands due to G:U pairing, suggesting that this strategy may even
      be used by replicators in the present day.

PMID- 24078152
TI  - Authors' response to: the case of acoustic neuroma: comment on mobile phone use
      and risk of brain neoplasms and other cancers.

PMID- 24078153
TI  - The case of acoustic neuroma: comment on: mobile phone use and risk of brain
      neoplasms and other cancers.

PMID- 24078154
TI  - Breathing manoeuvre-dependent changes in myocardial oxygenation in healthy
      humans.
AB  - AIMS: CO2 is an intrinsic vasodilator for cerebral and myocardial blood vessels.
      Myocardial vasodilation without a parallel increase of the oxygen demand leads to
      changes in myocardial oxygenation. Because apnoea and hyperventilation modify
      blood CO2, we hypothesized that voluntary breathing manoeuvres induce changes in
      myocardial oxygenation that can be measured by oxygenation-sensitive
      cardiovascular magnetic resonance (CMR). METHODS AND RESULTS: Fourteen healthy
      volunteers were studied. Eight performed free long breath-hold as well as a 1-
      and 2-min hyperventilation, whereas six aquatic athletes were studied during a 60
      s breath-hold and a free long breath-hold. Signal intensity (SI) changes in T2*
      weighted, steady-state free precession, gradient echo images at 1.5 T were
      monitored during breathing manoeuvres and compared with changes in capillary
      blood gases. Breath-holds lasted for 35, 58 and 117 s, and hyperventilation for
      60 and 120 s. As expected, capillary pCO2 decreased significantly during
      hyperventilation. Capillary pO2 decreased significantly during the 117-s breath
      hold. The breath-holds led to a SI decrease (deoxygenation) in the left
      ventricular blood pool, while the SI of the myocardium increased by 8.2% (P =
      0.04), consistent with an increase in myocardial oxygenation. In contrast,
      hyperventilation for 120 s, however, resulted in a significant 7.5% decrease in
      myocardial SI/oxygenation (P = 0.02). Change in capillary pCO2 was the only
      independently correlated variable predicting myocardial oxygenation changes
      during breathing manoeuvres (r = 0.58, P < 0.01). CONCLUSION: In healthy
      individuals, breathing manoeuvres lead to changes in myocardial oxygenation,
      which appear to be mediated by CO2. These changes can be monitored in vivo by
      oxygenation-sensitive CMR and thus, may have value as a diagnostic tool.

PMID- 24078155
TI  - The educational consequences of teen childbearing.
AB  - A huge literature shows that teen mothers face a variety of detriments across the
      life course, including truncated educational attainment. To what extent is this
      association causal? The estimated effects of teen motherhood on schooling vary
      widely, ranging from no discernible difference to 2.6 fewer years among teen
      mothers. The magnitude of educational consequences is therefore uncertain,
      despite voluminous policy and prevention efforts that rest on the assumption of a
      negative and presumably causal effect. This study adjudicates between two
      potential sources of inconsistency in the literature-methodological differences
      or cohort differences-by using a single, high-quality data source: namely, The
      National Longitudinal Study of Adolescent Health. We replicate analyses across
      four different statistical strategies: ordinary least squares regression;
      propensity score matching; and parametric and semiparametric maximum likelihood
      estimation. Results demonstrate educational consequences of teen childbearing,
      with estimated effects between 0.7 and 1.9 fewer years of schooling among teen
      mothers. We select our preferred estimate (0.7), derived from semiparametric
      maximum likelihood estimation, on the basis of weighing the strengths and
      limitations of each approach. Based on the range of estimated effects observed in
      our study, we speculate that variable statistical methods are the likely source
      of inconsistency in the past. We conclude by discussing implications for future
      research and policy, and recommend that future studies employ a similar
      multimethod approach to evaluate findings.

PMID- 24078156
TI  - Alterations in expression profile of iron-related genes in colorectal cancer.
AB  - Iron can play a role in colorectal cancer (CRC) development. The expression of
      genes involved in iron metabolism and its regulation in CRC has not been
      investigated well. Also the correlation between the level of iron-related genes
      expression and cancer progression is not known. In this study we collected paired
      samples of primary adenocarcinoma and adjacent normal mucosa from 73 patients. We
      assessed the mRNA or miRNA levels of 21 genes and verify their association with
      clinicopathological characteristics of CRC patients. Our experiments revealed,
      that the level of divalent metal transporter 1 transcript is well correlated with
      mRNA levels of iron regulatory proteins (IRPs) in tumor specimens. We have shown,
      that IRP2 can also be engaged in the mRNA stabilization of other iron transporter
      transferrin receptor 1 (TfR1) in early stage of disease, however, in more
      advanced stages of CRC, mRNA level of TfR1 is related to miR-31 level. For the
      first time we have shown, that ferroportin concentration is significantly
      associated with miR-194 level, causing the reduction of this transporter amount
      in tumor tissues of patients with more advanced stages of CRC. We have also shown
      the alterations in expressing profile of miR-31, miR-133a, miR-141, miR-145, miR
      149, miR-182 and miR-194, which were observed even in the early stage of disease,
      and identified a set of genes, which take place in correct assigning of patients
      in dependence of CRC stage. These iron-related genes could become potential
      diagnostic or prognostic indicators for patients with CRC.

PMID- 24078157
TI  - Screening of candidate proteins interacting with IE-2 of Bombyx mori
      nucleopolyhedrovirus.
AB  - IE-2 of Bombyx mori nucleopolyhedrovirus (BmNPV) has been shown to play important
      roles in baculovirus infection, which are involved in gene expression and viral
      replication. However, the mechanism remains unknown. In this paper, by TargetP
      software, four genes, i.e.-2, odv-e26, odv-e56 and BmNPV-gp101 (Ac-orf116) of
      BmNPV and Autographa californica multiple NPV (AcMNPV) were predicted to be
      located in mitochondria. By BLAST tool using BmNPV IE-2 protein sequence, 14 NPVs
      were found to have IE-2 homologues in GenBank, and most of them were predicted to
      be located in mitochondria, except for that of Antheraea pernyi NPV (AnpeNPV) and
      Anticarsia gemmatalis NPV (AngeNPV). To observe the subcellular localization of
      BmNPV IE-2, a recombinant virus overexpressed the IE-2 and eGFP fusion protein
      was constructed. In infected BmN cells, the fluorescence specifically enriched in
      the cellular mitochondria. This evidence was accordant with the prediction.
      Further, Pull-down assay was used to select protein candidates interacting with
      IE-2 in B. mori cells infected with BmNPV. Of several isolated protein
      components, sixteen candidates were identified by MALDI-TOF mass-spectrometry,
      eight baculoviral proteins (ALK-EXO, F protein, IAP-1, LEF-3, LEF-9, ODV-NC42,
      TLP, and VP39), and eight proteins from B. mori (Actin, ADP/ATP translocase, ATP
      synthase subunit beta, Beta-tubulin, DNA topoisomerase 2, Histone H4, Soluble
      guanylyl cyclae alpha-1 subunit, Transketolase). From the functional point of
      view, most of these proteins were generally divided into two groups,
      mitochondrial interaction proteins and viral DNA replication proteins. These
      results implied that the IE-2 had multiple functions involved in regulating viral
      gene expression, viral replication and also as a component of mitochondrial
      factors to regulate the cellular energy supply and apoptosis.

PMID- 24078159
TI  - Genetic variation in the vitamin D receptor gene and vitamin D serum levels in
      Egyptian women with polycystic ovary syndrome.
AB  - Obesity, insulin resistance, and hyperandrogenism are considered crucial
      parameters of polycystic ovary syndrome (PCOS) which might be related to vitamin
      D metabolism. The aim of this study was to investigate the associations between
      polymorphisms (TaqI and ApaI) in the vitamin D receptor gene (VDR) and PCOS among
      Egyptian women. We aimed also to elucidate the impact of these polymorphisms on
      vitamin D level, hormonal and metabolic parameters of PCOS. One hundred and fifty
      Egyptian women with PCOS and 150 unrelated controls were enrolled in this study.
      Polymorphisms of VDR Taq-I T/C (rs731236) and Apa-I A/C (rs7975232) gene were
      genotyped using polymerase chain reaction restriction fragment length
      polymorphism (PCR-RFLP). Serum 25 hydroxy vitamin D [25(OH) D] levels were
      measured by high-performance liquid chromatography. PCOS women had significantly
      lower levels of 25(OH) D compared to healthy women. Our results revealed that Taq
      I CC genotype and C allele were associated with increased risk of PCOS, while the
      Apa-I polymorphism was not. Haplotype Taq-I C/ Apa-I C was associated with a
      higher PCOS risk more than controls. Moreover, there was a significant decrease
      of 25(OH) D levels in carriers of haplotype Taq-I C/ Apa-I C (with variant
      alleles) compared to the non-carriers. Results showed also that there was an
      obesity- VDR Taq-I genotypes interactions. These results suggested that, VDR Taq
      I gene polymorphism is associated with increased risk of PCOS in Egyptian women.

PMID- 24078160
TI  - Sulfadiazine binds and unfolds bovine serum albumin: an in vitro study.
AB  - Sulfonamide derivatives, such as sulfadiazine (SD) are used as antibiotics and,
      very recently, anti-amyloid properties of these have been reported. We have
      evaluated binding of SD with bovine serum albumin (BSA) followed by unfolding of
      protein. Studies were accomplished at physiological conditions of temperature (37
      degrees C) and pH (7.4), employing UV, fluorescence, circular dichroism (CD) and
      Fourier transform infra-red (FTIR) spectroscopies. In presence of drug, UV
      spectrum of BSA was altered from the spectrum of native BSA due to the
      interaction between albumin and drug. Excitation of protein at 295 nm showed that
      fluorescence quenching of BSA by SD is a result of the formation of SD-BSA
      complex. The data were analyzed using Stern-Volmer and Lineweaver-Burk methods.
      From both methods it was evaluated that the quenching involved in BSA-SD binding
      was static. BSA had only one binding site for SD. Synchronous fluorescence
      spectra have shown a red shift and advocated that hydrophobicity around both Trp
      and Tyr residues was decreased. CD results revealed that the conformation of
      macromolecule remain undisturbed at low concentrations (up to 20 MUM of the SD)
      and there was small perturbation in the secondary structure from 20 to 50 MUM of
      SD followed by a large change and consequent unfolding on further increase in the
      drug concentration. Both synchronous and CD measurements were consistent to each
      other. FTIR spectra revealed the shifting of amide I band which is also an
      indication of conformational change of the protein.

PMID- 24078158
TI  - Analysis of expression profiles of selected genes associated with the
      regenerative property and the receptivity to gene transfer during somatic
      embryogenesis in Triticum aestivum L.
AB  - The physiological, biochemical and molecular mechanisms regulating the initiation
      of a regenerative pathway remain partially unknown. Efforts to identify the
      biological features that confer transformation ability, or the tendency of some
      cells to induce transgene silencing, would help to improve plant genetic
      engineering. The objective of our study was to monitor the evolution of plant
      cell competencies in relation to both in vitro tissue culture regeneration and
      the genetic transformation properties. We used a simple wheat regeneration
      procedure as an experimental model for studying the regenerative capacity of
      plant cells and their receptivity to direct gene transfer over the successive
      steps of the regenerative pathway. Target gene profiling studies and biochemical
      assays were conducted to follow some of the mechanisms triggered during the
      somatic-to-embryogenic transition (i.e. dedifferentiation, cell division
      activation, redifferentiation) and affecting the accessibility of plant cells to
      receive and stably express the exogenous DNA introduced by bombardment. Our
      results seem to indicate that the control of cell-cycle (S-phase) and host
      defense strategies can be crucial determinants of genetic transformation
      efficiency. The results from studies conducted at macro-, micro- and molecular
      scales are then integrated into a holistic approach that addresses the question
      of tissue culture and transgenesis competencies more broadly. Through this
      multilevel analysis we try to establish functional links between both
      regenerative capacity and transformation receptiveness, and thereby to provide a
      more global and integrated vision of both processes, at the core of
      defense/adaptive mechanisms and survival, between undifferentiated cell
      proliferation and organization.

PMID- 24078161
TI  - KRAS mutations in colorectal cancer from Tunisia: relationships with
      clinicopathologic variables and data on TP53 mutations and microsatellite
      instability.
AB  - Mutations in KRAS gene are among the critical transforming alterations occurring
      during CRC tumorigenesis. Here we screened 51 primary CRC tumors from Tunisia for
      mutations in KRAS (codons 12 and 13) using PCR-direct sequencing. Our aim was to
      analyze tumor mutation frequencies and spectra in Tunisian patients with CRC.
      KRAS status and mutation site/type were than correlated with familial and
      clinicopathologic variables and data on TP53 mutations and nuclear protein
      accumulation and microsatellite instability (MSI). A KRAS somatic mutation has
      been detected in the CRC tumor of 31.5 % (16/51) of the patients. 81.2 % had a
      single mutation at codon 12 and 23 % had a single mutation at codon 13. The most
      common single mutation (50 %) was a G>A transition in codon 12 (c.35G>A;
      p.Gly12Asp). 81.25 % of the KRAS mutations were transitions and 23 % were
      transversions. All the mutations in codon 13 were a c.38G>A transition, whereas
      both G>A transitions and G>T and G>C transversions were found in codon 12. The
      mutation spectrum was different between MSS and MSI-H tumors and more varied
      mutations have been detected in MSS tumors. Some amino acid changes were detected
      only in MSS tumors, i.e. p.Gly12Ser, p.Gly12Cys and p.Gly12Ala. Whereas, the KRAS
      mutation p.Gly13Asp have been detected only in MSI-H. 43.75 % of the patients
      harboured combined mutations in KRAS and TP53 genes and the tumor of 71.42 % of
      them showed TP53 overexpression. In conclusion, the frequency and types of KRAS
      mutations were as reported for non-Tunisian patients. However, no significant
      associations have been detected between KRAS mutations and clinicopathologic
      variables and MSI in Tunisian patients as previously reported.

PMID- 24078162
TI  - Systematic expression analysis of genes related to multidrug-resistance in
      isogenic docetaxel- and adriamycin-resistant breast cancer cell lines.
AB  - Docetaxel (Doc) and adriamycin (Adr) are two of the most effective
      chemotherapeutic agents in the treatment of breast cancer. However, their
      efficacy is often limited by the emergence of multidrug resistance (MDR). The
      purpose of this study was to investigate MDR mechanisms through analyzing
      systematically the expression changes of genes related to MDR in the induction
      process of isogenic drug resistant MCF-7 cell lines. Isogenic resistant sublines
      selected at 100 and 200 nM Doc (MCF-7/100 nM Doc and MCF-7/200 nM Doc) or at 500
      and 1,500 nM Adr (MCF-7/500 nM Adr and MCF-7/1,500 nM) were developed from human
      breast cancer parental cell line MCF-7, by exposing MCF-7 to gradually increasing
      concentrations of Doc or Adr in vitro. Cell growth curve, flow cytometry and MTT
      cytotoxicity assay were preformed to evaluate the MDR characteristics developed
      in the sublines. Some key genes on the pathways related to drug resistance
      (including drug-transporters: MDR1, MRP1 and BCRP; drug metabolizing-enzymes:
      CYP3A4 and glutathione S-transferases (GST) pi; target genes: topoisomerase II
      (TopoIIalpha) and Tubb3; apoptosis genes: Bcl-2 and Bax) were analyzed at RNA and
      protein expression levels by real time RT-qPCR and western blot, respectively.
      Compared to MCF-7/S (30.6 h), cell doubling time of MCF-7/Doc (41.6 h) and MCF
      7/Adr (33.8 h) were both prolonged, and the cell proportion of resistant sublines
      in G1/G2 phase increased while that in S-phase decreased. MCF-7/100 nM Doc and
      MCF-7/200 nM Doc was 22- and 37-fold resistant to Doc, 18- and 32-fold to Adr,
      respectively. MCF-7/500 nM Adr and MCF-7/1,500 nM Adr was 61- and 274-fold
      resistant to Adr, three and 12-fold to Doc, respectively. Meantime, they also
      showed cross-resistance to the other anticancer drugs in different degrees.
      Compared to MCF-7/S, RT-qPCR and Western blot results revealed that the
      expression of MDR1, MRP1, BCRP, Tubb3 and Bcl-2 were elevated in both MCF-7/Doc
      and MCF-7/Adr, and TopoIIalpha, Bax were down-regulated in both the sublines,
      while CYP3A4, GST pi were increased only in MCF-7/Doc and MCF-7/Adr respectively.
      Furthermore, the changes above were dose-dependent. The established MCF-7/Doc or
      MCF-7/Adr has the typical MDR characteristics, which can be used as the models
      for resistance mechanism study. The acquired process of MCF-7/S resistance to Doc
      or Adr is gradual, and is complicated with the various pathways involved in.
      There are some common resistant mechanisms as well as own drug-specific changes
      between both the sublines.

PMID- 24078163
TI  - Assessment of 11-beta hydroxysteroid dehydrogenase (11-betaHSD1) 4478T>G and
      tumor necrosis factor-alpha (TNF-alpha)-308G>A polymorphisms with obesity and
      insulin resistance in Asian Indians in North India.
AB  - 11-beta hydroxysteroid dehydrogenase (11-betaHSD1), tumor necrosis factor-alpha
      (TNF-alpha) and their role in obesity, regional adiposity and insulin resistance
      has been sparsely evaluated. We determined the polymorphic status of 11-betaHSD1
      4478T>G and TNF-alpha-308G>A in Asian Indians in north India. In this cross
      sectional study (n = 498; 258 males, 240 females), association of genotypes (PCR
      RFLP) of 11-betaHSD1 and TNF-alpha were analyzed with obesity [BMI >= 25 kg/m(2),
      percentage body fat (%BF by DEXA); subcutaneous and intra-abdominal fat area (L(2
      3) level by single slice MRI) in a sub sample] and insulin resistance. 46 percent
      subjects had generalized obesity, 55 % abdominal obesity and 23.8 % were insulin
      resistant. Frequencies (%) of [T/T] and [T/G] genotypes of 11-betaHSD1 were 89.57
      and 10.43 respectively. Homozygosity for 11-betaHSD1 4478G/G was absent with no
      association with parameters of obesity and insulin resistance. Frequencies (%) of
      TNF-alpha [G] and [A] alleles were 88 and 12 respectively. Higher frequency of
      variant -308[A/A] was observed in females versus males (p = 0.01). Females with
      at least one single A allele of TNF-alpha-308G>A had significantly high %BF and
      total skinfold, whereas higher values of waist hip ratio, total cholesterol,
      triglycerides and VLDL were observed in males. Subjects with even a single A
      allele in TNF-alpha genotype showed higher subscapular skinfold predisposing them
      to truncal subcutaneous adiposity (p = 0.02). Our findings of association of TNF
      alpha-308G>A variant in females with obesity indices suggests a gender-specific
      role of this polymorphism in obesity. High truncal subcutaneous adiposity is
      associated with A allele of TNF-alpha-308G>A in this population.

PMID- 24078164
TI  - Circulating C5L2 gene polymorphism is associated with type 2 diabetes mellitus in
      Saudi population.
AB  - The aim of the present study was to examine the relationship between the novel
      single nucleotide polymorphism, 698C>T that causes an amino acid change from
      proline to leucine at codon 233 and type 2 diabetes mellitus (T2DM) in the Saudi
      population. From the general population in the Saudi Arabia a total of 551
      samples were collected and categorized them as T2DM (n = 376) and healthy
      controls (n = 175). Five ml of the blood sample was collected and used for the
      Biochemical and Molecular analysis. With the help of serum sample lipid profile:
      Fasting blood sugar (FBS), Total Cholesterol (TC), Triglycerides (TG), High
      Density Lipoprotein Cholesterol (HDL-C), Low Density Lipoprotein Cholesterol (LDL
      C) and VLDL were performed. PCR-RFLP was performed after separating the genomic
      DNA from the EDTA blood. The genotype distribution of C698T polymorphism was
      performed by the Chi square test with SPSS version 16.0 software for comparing
      T2DM subjects and healthy controls. In our study, genotypic distributions of C5L2
      C698T polymorphism and allele frequency of patients and controls were found to be
      significant difference in the allele and the genotypic distribution. [For T Vs C;
      p = 0.01; Odds ratio = 3.594 (95 % CI; 1.256-10.28); and CT+TT Vs CC; p = 0.009;
      Odds ratio = 3.707 (95 % CI; 1.285-10.69)]. TT genotype was completely absent in
      both the cases and the controls. In conclusion, our study indicates that 698C>T
      polymorphism of C5L2 gene is associated with the T2DM in individuals of Saudi
      population which was found to be similar with other studies.

PMID- 24078165
TI  - Molecular characterization and expression analysis of a KIFC1-like kinesin gene
      in the testis of Eumeces chinensis.
AB  - The member of the kinesin-14 subfamily, KIFC1, is a carboxyl-terminal motor
      protein that plays an important role in the elongation of nucleus and acrosome
      biogenesis during the spermiogenesis of mammals. Here, we had cloned and
      sequenced the cDNA of a mammalian KIFC1 homologue (termed ec-KIFC1) from the
      total RNA of the testis of the reptile Eumeces chinensis. The full-length
      sequence was 2,339 bp that contained a 216 bp 5'-untranslated region (5'UTR), a
      194 bp 3'-untranslated region (3'UTR) and a 1,929 bp open reading frame that
      encoded a special protein of 643 amino acids (aa). The calculated molecular
      weight of the putative ec-KIFC1 was 71 kDa and its estimated isoelectric point
      was 9.47. The putative ec-KIFC1 protein owns a tail domain from 1 to 116 aa, a
      stalk domain from 117 to 291 aa and a conserved carboxyl motor domain from 292 to
      642 aa. Protein alignment demonstrated that ec-KIFC1 had 45.6, 42.8, 44.6, 36.9,
      43.7, 46.4, 45.1, 55.6 and 49.8 % identity with its homologues in Mus musculus,
      Salmo salar, Danio rerio, Eriocheir sinensis, Rattus norvegicus, Homo sapiens,
      Bos taurus, Gallus gallus and Xenopus laevis, respectively. Tissue expression
      analysis showed the presence of ovary, heart, liver, intestine, oviduct, testis
      and muscle. The phylogenetic tree revealed that ec-KIFC1 was more closely related
      to vertebrate KIFC1 than to invertebrate KIFC1. In situ hybridization showed that
      the ec-KIFC1 mRNA was localized in the periphery of the nuclear membrane and the
      center of the nucleus in early spermatids. In mid spermatids, the ec-KIFC1 had
      abundant expression in the center of nucleus, and was expressed in the tail and
      the anterior part of spermatids. In the late spermatid, the nucleus gradually
      became elongated, and the ec-KIFC1 mRNA signal was still centralized in the
      nucleus. In mature spermatids, the signal of the ec-KIFC1 gradually became weak,
      and was mainly located at the tail of spermatids. Therefore, the ec-KIFC1
      probably plays a critical role in the spermatogenesis of E. chinensis.

PMID- 24078166
TI  - Taste performance in Parkinson's disease.
AB  - While olfactory deficit is already known to be associated with early-stage
      Parkinson's disease (PD), taste perception has not fully clarified so far. In
      this study, we investigated the taste performance in 61 patients with PD and 66
      healthy controls (HC) using the Whole Mouth (WMT) and Taste Strip Tests (TST). In
      addition, we evaluated their olfactory function by means of the Sniffin' Sticks
      Test (SST). TST score was significantly lower in PD patients than in HC (TST
      score 11.0 +/- 2.8 vs. 12.2 +/- 2.1; p<0.018) while WMT showed no difference. The
      olfactory evaluation confirmed the results reported in the literature with a
      significant reduction of the SST score in PD patients than in HC (SST score 7.0
      +/- 2.8 vs. 11.3 +/- 2.8; p<0.0001). The conflicting results revealed by TST and
      WMT could rely on a taste impairment not detectable at supra-threshold
      concentration of tastes, typical of the daily life. Possible biological
      correlates of taste impairment in PD are discussed.

PMID- 24078167
TI  - Lack of association of morphologic and functional retinal changes with motor and
      non-motor symptoms severity in Parkinson's disease.
AB  - Visual symptoms are common among the nonmotor symptoms in Parkinson's disease.
      The aims of this study were to assess the diagnostic accuracy and relationship of
      retinal morphologic and functional changes with motor and non-motor symptoms
      disturbances in Parkinson's disease. Thirty patients with Parkinson's disease,
      with a median Hoehn-Yahr stage of 2 (1-4), were compared to 30 age- and gender
      matched controls. Retinal thinning and function were measured using optical
      coherence tomography (OCT), visual evoked potentials (VEP), and pattern
      electroretinography. Motor impairment and motor laterality were measured using
      the Short Parkinson's Evaluation Scale/Scales for Outcomes in Parkinson's
      disease, and non-motor symptoms severity using the nonmotor symptoms
      questionnaire. Only pattern electroretinography, P50 and N95 amplitudes, were
      lower in patients with Parkinson's disease, compared to controls (p = 0.01,
      respectively). Age, disease duration, levodopa dose, motor, and non-motor
      impairment were not significantly associated with retinal thinning and functional
      changes. The patients vs. controls area under the curve of OCT, VEP, and pattern
      electroretinography receiver-operating-characteristic curves were<0.50. In
      conclusion, morphologic and functional retina changes are not significantly
      correlated with motor and non-motor symptoms impairment severity, and do not
      discriminate between Parkinson's disease and controls.

PMID- 24078169
TI  - Cochrane in CORR(r): Arthroplasty versus fusion in single-level cervical
      degenerative disc disease.

PMID- 24078170
TI  - Injury complexity factors predict heterotopic ossification restricting motion
      after elbow trauma.
AB  - BACKGROUND: Heterotopic ossification (HO) is a common extrinsic cause of elbow
      stiffness after trauma. However, factors associated with the development of HO
      are incompletely understood. QUESTIONS/PURPOSES: We retrospectively identified
      (1) patient-related demographic factors, (2) injury-related factors, and (3)
      treatment-related factors associated with the development of HO severe enough to
      restrict motion after surgery for elbow trauma. We also determined what
      percentage of the variation in HO restricting motion was explained by the
      variables studied. METHODS: Between 2001 and 2007, we performed surgery on 417
      adult patients for elbow fractures; of these, 284 (68%) were available for
      radiographs at a minimum of 4 months and clinical review at a minimum of 6 months
      after surgery (mean, 7.9 months; range, 6-31 months). HO was classified according
      to the Hastings and Graham system. Patients with HO restricting motion (defined
      as a Hastings and Graham Class II or III) were compared with patients without HO
      restricting motion in terms of demographics, fracture location, elbow
      dislocation, open wound, mechanism of injury, ipsilateral fracture, head trauma,
      time from injury to surgery, number of surgeries within 4 weeks, total number of
      surgeries, bone graft, and infection, using bivariate and multivariable analyses.
      A total of 96 patients had radiographic HO, and in 27 (10% of those available for
      followup), it restricted motion. RESULTS: There were no patient-related
      demographic factors that predicted the formation of symptomatic HO. Ulnohumeral
      dislocation in addition to fracture (odds ratio, 2.38; 95% CI, 1.01-5.64; p =
      0.048) but not fracture location was associated with HO. Longer time from injury
      to definitive surgery and number of surgical procedures in the first 4 weeks were
      also independent predictors of HO (p = 0.01 and 0.004, respectively). These
      factors explained 20% of the variance in risk for HO restricting motion.
      CONCLUSIONS: HO restricting motion after operative elbow fracture treatment
      associates with factors that seem related to injury complexity, in particular,
      ulnohumeral dislocation, delay, and number of early surgeries; however, a
      substantial portion of the variation among patients with elbow fracture who
      develop restrictive HO remains unexplained. LEVEL OF EVIDENCE: Level III,
      therapeutic study. See Instructions for Authors for a complete description of
      levels of evidence.

PMID- 24078171
TI  - Adverse reactions of artificial bone graft substitutes: lessons learned from
      using tricalcium phosphate geneX(r).
AB  - BACKGROUND: Artificial bone graft substitutes are widely used to fill bony
      defects after curettage of benign tumors. We sought to evaluate the efficacy of
      one such bone graft substitute, geneX(r), which contains tricalcium phosphate and
      calcium sulphate; however, during the course of this study we observed a high
      number of complications. QUESTIONS/PURPOSES: The primary aim of this prospective
      series was assessment of the effectiveness of geneX(r) concerning resorption
      profile and bone healing and remodeling after surgery. We present the types and
      frequencies of complications observed in patients treated for bone tumors by
      curettage and filling the defect using geneX(r). METHODS: We planned to study 40
      patients; however, after enrollment of the first 31 patients, the study was
      stopped as a result of serious complications. There were 20 female and 11 male
      patients with a mean age at surgery of 40 years (range, 6-71 years). Plain
      radiographs were obtained at different intervals during followup and CT scans
      were obtained 6 and 12 months postoperatively. Complications were assessed using
      a 5-point scale according to Goslings and Gouma. RESULTS: Five of the 31 patients
      (16%) had complications develop after surgery. In three cases, a sterile
      inflammation adjacent to the geneX(r) occurred, with delayed wound healing in two
      patients and local pain. In the third patient, geneX(r) produced moderate to
      severe skin damage in the area of the scar, needing revision surgery. In two
      other patients, inflammatory cystic formations developed in the soft tissues with
      sizes up to 15 cm, which gradually reduced in size with time. Overall, there were
      four Grade 1 complications and one Grade 2 according to Goslings and Gouma.
      CONCLUSIONS: We concluded from this series of patients that geneX(r) causes soft
      tissue inflammation and pain with its use. Based on this experience we believe
      that this type of bone substitute should not be used in the treatment of bony
      defects. LEVEL OF EVIDENCE: Level IV, therapeutic study. See the Instructions for
      Authors for a complete description of levels of evidence.

PMID- 24078174
TI  - Tumor progression and transformation of low-grade glial tumors  associated with
      pregnancy.
AB  - Brain tumor growth or progression has been shown to occur in low-grade glial
      tumors and meningiomas. While progression has been documented in this population,
      transformation to a more aggressive high-grade glial tumor that can lead to
      increased morbidity and mortality has not been identified. In this case series,
      we document transformation from low-grade gliomas to high-grade gliomas (WHO
      grade III and IV) in young women during pregnancy. We further discuss the
      possible etiologies of this phenomenon.

PMID- 24078173
TI  - Fractionated stereotactic radiosurgery for recurrent ependymoma  in children.
AB  - Outcomes for children with relapsed ependymoma are poor. Re-irradiation is a
      potentially viable salvage option in these patients. Data were reviewed for 12
      patients (median age 5.6 years) with relapsed ependymoma who received
      fractionated stereotactic radiosurgery (fSRS) following maximal surgical
      resection from 1995 to 2012. Four patients experienced a second recurrence,
      including 2 in-field and 2 distant failures. Median time to second recurrence (32
      months) was significantly longer than time to first recurrence (24 months) (p =
      0.008). Three-year local control was 89 %, and median event free survival from
      fSRS was 3.4 years. Radiation necrosis was observed in 6 patients, 3 who were
      symptomatic. In conclusion, fSRS offers durable response with a tolerable
      toxicity profile in children with recurrent EPN.

PMID- 24078175
TI  - Mapping the patterns of care, the receipt of palliative care  and the site of
      death for patients with malignant glioma.
AB  - High-grade malignant glioma patients face a poor prognosis, preceded by rapid
      functional and neurobehavioural changes, making multidisciplinary care
      incorporating supportive and palliative care important. This study aimed to
      quantify the association between symptoms,receipt of supportive and palliative
      care and site of death. We undertook a retrospective cohort study between 2003
      and 2009 of incident malignant glioma cases who survived for at least 120 days
      between their first hospitalisation and their death (n = 678) in Victoria,
      Australia, using linked hospital, emergency department and death data. The median
      age of patients was 62 years, 40% were female, and the median survival was 11
      months. Twenty-six percent of patients died outside of hospital, 49% in a
      palliative care bed/hospice setting and 25% in an acute hospital bed. Patients
      having 1 or more symptoms were more than five times as likely to receive
      palliative care. Patients who receive palliative care are 1.7 times more likely
      to die outside of hospital. In conclusion malignant glioma patients with a high
      burden of symptoms are more likely to receive palliative care and, in turn,
      patients who receive palliative care are more likely to die at home.

PMID- 24078172
TI  - ZNF804A and cortical structure in schizophrenia: in vivo and postmortem studies.
AB  - Recent evidence indicated that the ZNF804A (rs1344706) risk allele A is
      associated with better cognitive performance in patients with schizophrenia.
      Moreover, it has been demonstrated that ZNF804A may also be related to relatively
      intact gray matter volume in patients. To further explore these putatively
      protective effects, the impact of ZNF804A on cortical thickness and folding was
      examined in this study. To elucidate potential molecular mechanisms, an allelic
      specific gene expression study was also carried out. Magnetic resonance imaging
      cortical thickness and folding were computed in 55 genotyped patients with
      schizophrenia and 40 healthy controls. Homozygous risk allele carriers (AA) were
      compared with AC/CC carriers. ZNF804A gene expression was analyzed in a
      prefrontal region using postmortem tissue from another cohort of 35 patients. In
      patients, AA carriers exhibited significantly thicker cortex in prefrontal and
      temporal regions and less disturbed superior temporal cortical folding, whereas
      the opposite effect was observed in controls, ie, AA carrier status was
      associated with thinner cortex and more severe altered cortical folding. Along
      with this, our expression analysis revealed that the risk allele is associated
      with lower prefrontal ZNF804A expression in patients, whereas the opposite effect
      in controls has been observed by prior analyses. In conclusion, our analyses
      provide convergent support for the hypothesis that the schizophrenia-associated
      ZNF804A variant mediates protective effects on cortex structure in patients. In
      particular, the allele-specific expression profile in patients might constitute a
      molecular mechanism for the observed protective influence of ZNF804A on cortical
      thickness and folding and potentially other intermediate phenotypes. 

PMID- 24078176
TI  - Recalcitrance of nature: chemocatalysis for the production of biomass-based
      building blocks.

PMID- 24078179
TI  - Early-stage comparative sustainability assessment of new bio-based processes.
AB  - Our increasing demand for materials and energy has put critical roadblocks on our
      path towards a sustainable society. To remove these roadblocks, it is important
      to engage in smart research and development (R&D). We present an early-stage
      sustainability assessment framework that is used to analyze eight new bio-based
      process alternatives developed within the CatchBio research consortium in the
      Netherlands. This assessment relies on a multi-criteria approach, integrating the
      performance of chemical conversions based on five indicators into an index value.
      These indicators encompass economics, environmental impact, hazards and risks
      thereby incorporating elements of green chemistry principles, and techno-economic
      and life cycle assessments. The analyzed bio-based options target the production
      of fuels and chemicals through chemical catalysis. For each bio-based process,
      two R&D stages (current laboratory and expected future) are assessed against a
      comparable conventional process. The multi-criteria assessment in combination
      with the uncertainty and scenario analysis shows that the chemical production
      processes using biomass as feedstock can provide potential sustainability
      benefits over conventional alternatives. However, further development is
      necessary to realize the potential benefits from biomass gasification and
      pyrolysis processes for fuel production. This early stage assessment is intended
      as an input for R&D decision making to support optimal allocation and utilization
      of resources to further develop promising bio-based processes. 

PMID- 24078180
TI  - Ligand effects on the hydrogenation of biomass-inspired substrates with
      bifunctional Ru, Ir, and Rh complexes.
AB  - We herein report on the application and structural investigation of a new set of
      complexes that contain bidentate N-heterocyclic carbenes (NHCs) and primary amine
      moieties of the type [M(arene)Cl(L)] [M=Ru, Ir, or Rh; arene=p-cymene or
      pentamethylcyclopentadienyl; L=1-(2-aminophenyl)-3-(n-alkyl)imidazol-2-ylidine].
      These complexes were tested and compared in the hydrogenation of acetophenone
      with hydrogen. Structural variations in the chelate ring size of the
      heteroditopic ligand revealed that smaller chelate ring sizes in combination with
      ring conjugation in the ligand are beneficial for the activity of this type of
      catalyst, favoring an inner-sphere coordination pathway. Additionally, increasing
      the steric bulk of the alkyl substituent on the NHC aided the reaction, showing
      almost no induction period and formation of a more active catalyst for the n
      butyl complex relative to complexes with smaller Me and Et substituents. As is
      common in hydrogenation reactions, the activity of the complexes decreases in the
      order Ru>Ir>Rh. The application of [Ru(p-cym)Cl(L)]PF6 , which outperforms its
      reported analogues, has been successfully extended to the hydrogenation of more
      challenging biomass-inspired substrates. 

PMID- 24078181
TI  - Mechanism-based selection of a potent kallikrein-related peptidase 7 inhibitor
      from a versatile library based on the sunflower trypsin inhibitor SFTI-1.
AB  - Potent and specific enzyme inhibition is a key goal in the development of
      therapeutic inhibitors targeting proteolytic activity. The backbone-cyclized
      peptide, Sunflower Trypsin Inhibitor (SFTI-1) affords a scaffold that can be
      engineered to achieve both these aims. SFTI-1's mechanism of inhibition is
      unusual in that it shows fast-on/slow-off kinetics driven by cleavage and
      religation of a scissile bond. This phenomenon was used to select a nanomolar
      inhibitor of kallikrein-related peptidase 7 (KLK7) from a versatile library of
      SFTI variants with diversity tailored to exploit distinctive surfaces present in
      the active site of serine proteases. Inhibitor selection was achieved through the
      use of size exclusion chromatography to separate protease/inhibitor complexes
      from unbound inhibitors followed by inhibitor identification according to
      molecular mass ascertained by mass spectrometry. This approach identified a
      single dominant inhibitor species with molecular weight of 1562.4 Da, which is
      consistent with the SFTI variant SFTI-WCTF. Once synthesized individually this
      inhibitor showed an IC50 of 173.9 +/- 7.6 nM against chromogenic substrates and
      could block protein proteolysis. Molecular modeling analysis suggested that
      selection of SFTI-WCTF was driven by specific aromatic interactions and
      stabilized by an enhanced internal hydrogen bonding network. This approach
      provides a robust and rapid route to inhibitor selection and design.

PMID- 24078182
TI  - Foreword for ICCP2012 Issue of Biopolymers Peptide Science Circular Proteins:
      Never Ending Possibilities.

PMID- 24078183
TI  - Continuous lipase-catalyzed esterification of soybean fatty acids under
      ultrasound irradiation.
AB  - This work investigates the continuous production of alkyl esters from soybean
      fatty acid (FA) charges using immobilized Novozym 435 as catalyst. The
      experiments were performed in a packed-bed bioreactor evaluating the effects of
      FA charge to alcohol (methanol and ethanol) molar ratio, from 1:1 to 1:6,
      substrate flow rate in the range of 0.5-2.5 mL/min and output irradiation power
      up to 154 W, at fixed temperature of 65  degrees C, on the reaction conversion.
      Results showed that almost complete conversions to fatty acids ethyl esters were
      achieved at mild ultrasonic power (61.6 W), FA to ethanol molar ratio of 1:6,
      operating temperature (65  degrees C) and remained nearly constant for long-term
      reactions without negligible enzyme activity losses. 

PMID- 24078184
TI  - Stable operation of microbial fuel cells at low temperatures (5-10  degrees C)
      with light exposure and its anodic microbial analysis.
AB  - Performances of microbial fuel cells (MFCs) were studied at 5-10 and 25-30 
      degrees C. Results showed stable operation of the MFCs at low temperatures with
      only slight reductions of voltage and power generation (11 versus 14 % for double
      chamber MFC, while 14 versus 21 % for single-chamber MFC, 1,000 Omega) compared
      to those at mesophilic temperatures. MFCs operated at low temperatures showed
      lower COD removal rates accompanied by higher coulombic efficiencies (CEs). PCR
      DGGE analysis revealed that psychrotrophic microbes (mainly Arcobacter,
      Pseudomonas, and Geobacter) dominated on anodes of the MFCs at low temperatures.
      Interestingly, light-induced red substances appeared on anode of the MFCs
      operated at low temperature and were proven to be the main anodic microbes
      (Arcobacter and Pseudomonas). Co-existence of the aforementioned microbes could
      assist stable low-temperature operation of the MFCs. Cyclic voltammetry analysis
      supported the results of the CE and DGGE. Stable performance of MFCs at low
      temperatures might be achieved by the control of anodic bacteria.

PMID- 24078185
TI  - Biosynthesis of poly(3-hydroxybutyrate) (PHB) by Cupriavidus necator H16 from
      jatropha oil as carbon source.
AB  - Poly(3-hydroxybutyrate) (PHB) is a biodegradable polymer that can be synthesized
      through bacterial fermentation. In this study, Cupriavidus necator H16 is used to
      synthesize PHB by using Jatropha oil as its sole carbon source. Different
      variables mainly jatropha oil and urea concentrations, and agitation rate were
      investigated to determine the optimum condition for microbial fermentation in
      batch culture. Based on the results, the highest cell dry weight and PHB
      concentrations of 20.1 and 15.5 g/L, respectively, were obtained when 20 g/L of
      jatropha oil was used. Ethanol was used as external stress factor and the
      addition of 1.5 % ethanol at 38 h had a positive effect with a high PHB yield of
      0.987 g PHB/g jatropha oil. The kinetic studies for cell growth rate and PHB
      production were conducted and the data were fitted with Logistic and Leudeking
      Piret models. The rate constants were evaluated and the theoretical values were
      in accordance with the experimental data obtained

PMID- 24078186
TI  - Evaluation of genetic homogeneity in tissue culture regenerates of Jatropha
      curcas L. using flow cytometer and DNA-based molecular markers.
AB  - The present investigation aimed to evaluate the reliability of in vitro
      propagation methods for elite genotypes of Jatropha curcas L., that maintain
      genetic integrity of tissue culture (TC) regenerates among two regeneration
      systems developed through direct shoot bud regeneration using nodal/apical shoot
      segments (protocol-A) and in vitro-derived leaves (protocol-B) as explants.
      Random amplified polymorphic DNA (RAPD), intersimple sequence repeat (ISSR),
      simple sequence repeat (SSR) molecular markers, and flow cytometery (FCM) were
      employed to evaluate genetic homogeneity in TC-regenerates at different passages
      of subcultures. RAPD markers showed genetic homogeneity in fifth-generation TC
      regenerates of both protocols. ISSR markers showed genetic stability of leaf
      regenerates (protocol-B) at 10th generation. FCM analysis of TC-regenerates at
      10th generation in protocol-B and at 20th generation in both protocols, showed
      stability of ploidy level. SSR assessment of TC-regenerates at 20th generation in
      both protocols confirmed genetic homogeneity. The results confirmed the genetic
      stability of the TC-regenerates and demonstrated the reliability of the
      regeneration systems developed so far using explants of two different origins,
      for large-scale multiplication of elite genotypes of Jatropha.

PMID- 24078187
TI  - Extract from Eugenia punicifolia is an antioxidant and inhibits enzymes related
      to metabolic syndrome.
AB  - The present study aimed to investigate in vitro biological activities of extract
      of Eugenia punicifolia leaves (EEP), emphasizing the inhibitory activity of
      enzymes related to metabolic syndrome and its antioxidant effects. The
      antioxidant activity was analyzed by free radicals scavengers in vitro assays:
      DPPH., ABTS(.+), O2(.-), and NO. and a cell-based assay. EEP were tested in
      inhibitory colorimetric assays using alpha-amylase, alpha-glucosidase, xanthine
      oxidase, and pancreatic lipase enzymes. The EEP exhibited activity in ABTS(.+),
      DPPH., and O2(.-) scavenger (IC50 = 10.5 +/- 1.2, 28.84 +/- 0.54, and 38.12 +/-
      2.6 MUg/mL), respectively. EEP did not show cytotoxic effects, and it showed
      antioxidant activity in cells in a concentration-dependent manner. EEP exhibited
      inhibition of alpha-amylase, alpha-glucosidase, and xanthine oxidase activities
      in vitro assays (IC50 = 122.8 +/- 6.3; 2.9 +/- 0.1; 23.5 +/- 2.6), respectively;
      however, EEP did not inhibit the lipase activity. The findings supported that
      extract of E. punicifolia leaves is a natural antioxidant and inhibitor of
      enzymes, such as alpha-amylase, alpha-glucosidase, and xanthine oxidase, which
      can result in a reduction in the carbohydrate absorption rate and decrease of
      risks factors of cardiovascular disease, thereby providing a novel dietary
      opportunity for the prevention of metabolic syndrome.

PMID- 24078188
TI  - Characterization of biocatalysts prepared with Thermomyces lanuginosus lipase and
      different silica precursors, dried using aerogel and xerogel techniques.
AB  - The use of lipases in industrial processes can result in products with high
      levels of purity and at the same time reduce pollutant generation and improve
      both selectivity and yields. In this work, lipase from Thermomyces lanuginosus
      was immobilized using two different techniques. The first involves the
      hydrolysis/polycondensation of a silica precursor (tetramethoxysilane (TMOS)) at
      neutral pH and ambient temperature, and the second one uses tetraethoxysilane
      (TEOS) as the silica precursor, involving the hydrolysis and polycondensation of
      the alkoxide in appropriate solvents. After immobilization, the enzymatic
      preparations were dried using the aerogel and xerogel techniques and then
      characterized in terms of their hydrolytic activities using a titrimetric method
      with olive oil and by the formation of 2-phenylethyl acetate in a
      transesterification reaction. The morphological properties of the materials were
      characterized using scanning electron microscopy, measurements of the surface
      area and pore size and volume, thermogravimetric analysis, and exploratory
      differential calorimetry. The results of the work indicate that the use of
      different silica precursors (TEOS or TMOS) and different drying techniques
      (aerogel or xerogel) can significantly affect the properties of the resulting
      biocatalyst. Drying with supercritical CO2 provided higher enzymatic activities
      and pore sizes and was therefore preferable to drying, using the xerogel
      technique. Thermogravimetric analysis and differential scanning calorimetry
      analyses revealed differences in behavior between the two biocatalyst
      preparations due to the compounds present.

PMID- 24078189
TI  - Quantitative determination of glycine in aqueous solution using glutamate
      dehydrogenase-immobilized glyoxal agarose beads.
AB  - In this study, an enzymatic procedure for the determination of glycine (Gly) was
      developed by using a column containing immobilized glutamate dehydrogenase (GDH)
      on glyoxal agarose beads. Ammonia is produced from the enzymatic reactions
      between Gly and GDH with NAD(+) in phosphate buffer medium. The indophenol blue
      method was used for ammonia detection based on the spectrophotometric
      measurements of blue-colored product absorbing at 640 nm. The calibration graph
      is linear in the range of 0.1-10 mM of Gly concentrations. The effect of pH,
      temperature, and time interval was studied to find column stability, and also the
      interference effects of other amino acids was investigated. The interaction
      between GDH and glyoxal agarose beads was analyzed by Fourier transform infrared
      (FTIR) spectroscopy. The morphology of the immobilized and non-immobilized
      agarose beads were characterized by atomic force microscopy (AFM).

PMID- 24078190
TI  - L-Ribose production from L-arabinose by immobilized recombinant Escherichia coli
      co-expressing the L-arabinose isomerase and mannose-6-phosphate isomerase genes
      from Geobacillus thermodenitrificans.
AB  - L-Ribose is an important precursor for antiviral agents, and thus its high-level
      production is urgently demanded. For this aim, immobilized recombinant
      Escherichia coli cells expressing the L-arabinose isomerase and variant mannose-6
      phosphate isomerase genes from Geobacillus thermodenitrificans were developed.
      The immobilized cells produced 99 g/l L-ribose from 300 g/l L-arabinose in 3 h at
      pH 7.5 and 60  degrees C in the presence of 1 mM Co(2+), with a conversion yield
      of 33 % (w/w) and a productivity of 33 g/l/h. The immobilized cells in the packed
      bed bioreactor at a dilution rate of 0.2 h(-1) produced an average of 100 g/l L
      ribose with a conversion yield of 33 % and a productivity of 5.0 g/l/h for the
      first 12 days, and the operational half-life in the bioreactor was 28 days. Our
      study is first verification for L-ribose production by long-term operation and
      feasible for cost-effective commercialization. The immobilized cells in the
      present study also showed the highest conversion yield among processes from L
      arabinose as the substrate.

PMID- 24078191
TI  - Human immunodeficiency virus and hepatitis C virus  coinfection in Nepal.
AB  - OBJECTIVES: The study aimed at finding prevalence, mode of transmission, and
      pattern of CD4 cell count among hepatitis C virus (HCV) coinfected human
      immunodeficiency virus (HIV)-positive individuals in Nepal. METHODS: This was a
      descriptive cross-sectional study carried out in three Volunteer Counseling and
      Testing clinics, one from Dharan and two from Kathmandu, Nepal. Three hundred and
      thirteen individuals were recruited. RESULTS: Forty-two percent of HIV-infected
      persons had HCV coinfection. Significant associations with HIV and HCV
      coinfection were male gender (p <0.001) and injection drug use (IDU) (p <0.001).
      The mean CD4 cell count was significantly lower in HCV coinfected individuals,
      compared to those without coinfection, after 1.5 years (p =0.017), 2 years (p
      =0.0457), 3 years (p =0.011), and 3.5 years (p <0.001) of antiretroviral therapy.
      CONCLUSION: HCV coinfection was common in HIV-infected individuals in Nepal and
      was associated with male gender, IDU, and lower CD4 counts.

PMID- 24078192
TI  - Rothia aeria mitral valve endocarditis complicated by multiple  mycotic
      aneurysms: laboratory identification expedited using  MALDI-TOF MS.
AB  - Rothia aeria has only rarely been described as a human pathogen. We describe a
      case of Rothia aeria causing mitral valve endocarditis and multiple mycotic
      aneurysms, including cerebral mycotic aneurysms. In the case described, early
      identification of Rothia aeria was achieved using matrix-assisted laser
      desorption ionization-time of flight mass spectrometry (MALDI-TOF MS).

PMID- 24078193
TI  - Antibiotic hospital consumption expressed in defined daily doses (DDD)/100 bed
      days.

PMID- 24078194
TI  - Pediatric Sleep Survey Instrument--a screening tool for sleep disordered
      breathing.
AB  - PURPOSE: The aim of this study was to assess the construct validity and clinical
      application of the Pediatric Sleep Survey Instrument (PSSI) as a tool to screen
      for sleep disordered breathing (SDB) in children. METHODS: Polysomnography (PSG)
      outcomes and PSSI subscale scores were compared between a clinical cohort (N =
      87, 5-10 years, 62 M/25 F) and a nonsnoring community sample (N = 55, 5-10 years,
      28 M/27 F). Group comparisons assessed the ability of the PSSI subscales to
      discriminate between the clinical and community cohorts. Receiver operating
      characteristic (ROC) curves assessed construct validity, with the Apnea/Hypopnea
      Index (AHI) >5 events/h, OSA-18 score >60, and Pediatric Daytime Sleepiness Scale
      (PDSS) above the 70th percentile as the target references. RESULTS: The clinical
      group had more respiratory events, respiratory-related arousals, fragmented
      sleep, and lower oxygen saturation nadir than the community group (p < 0.001 for
      all). PSSI subscale scores of Morning Tiredness, Night Arousals, SDB, and
      Restless Sleep were higher (p < 0.001 for all) in the clinical cohort, confirming
      the tool's ability to identify clinically relevant sleep problems. ROC curves
      confirmed the diagnostic accuracy of the SDB subscale against an AHI > 5 events/h
      (area under the curve (AUC) = 0.7), an OSA-18 score >60 (AUC = 0.7), and a PDSS
      score in the 70th percentile (AUC = 0.8). The Morning Tiredness subscale
      accurately predicted a PDSS score in the 70th percentile (AUC = 0.8). A cutoff
      score of 5 on the SDB subscale showed a sensitivity of 0.94 and a specificity of
      0.76, correctly identifying 77 and 100 % of the clinical and community cohorts,
      respectively. CONCLUSION: The PSSI Sleep Disordered Breathing subscale is a valid
      tool for screening SDB and daytime sleepiness in children aged 5-10 years.

PMID- 24078195
TI  - Leftward displacement of septum primum in children with congenital heart disease.

PMID- 24078196
TI  - Bicuspid aortic valve: a neglected feature of Shone's complex?

PMID- 24078197
TI  - Assessment of non-clinical attributes in paramedicine using multiple mini
      interviews.
AB  - BACKGROUND: Non-clinical attributes are increasingly emphasised as an important
      factor in paramedic practice. However, the assessment of these attributes often
      lacks the evidence base to support it. Exploring the relationship between non
      clinical attributes and clinical skills is also of theoretical and practical
      importance. OBJECTIVE: To first seek evidence of reliability and validity for the
      assessment of non-clinical attributes using the multiple mini-interview (MMI) in
      paramedic contexts and second, to explore the association between non-clinical
      attributes and clinical skills in paramedicine. METHODS: Entry to practice level
      paramedic candidates completed a 10-station MMI to assess non-clinical attributes
      on day 1 and a 10-station simulation-based assessment (SBA) of clinical skills on
      day 2. Both were assessed using different global rating scales. Our primary
      outcomes included MMI inter-station reliability (calculated using
      generalisability theory) and Pearson's correlation between non-clinical
      attributes and clinically focused skills. RESULTS: 30 trainees completed the MMI
      and 26 of the 30 completed the SBA. Inter-station reliability for the MMI reached
      0.77. Pearson's correlations (disattenuated correlations in parentheses) between
      the overall MMI score and mean SBA global rating scores reached r=0.31 (r=0.48)
      and ranged by dimension from r=-0.11 (-0.17) (procedural skills) to
      r=0.54(r=0.83) (communication). CONCLUSIONS: The MMI demonstrated evidence of
      reliability and validity for the assessment of non-clinical attributes in
      paramedic contexts. Non-clinical attributes and paramedic clinical skills are
      likely distinct but related constructs, each contributing to the construct of
      paramedic practice. Programmes of assessment should include both to ensure the
      construct of paramedic practice is adequately represented.

PMID- 24078198
TI  - Paramedic Initiated Lisinopril For Acute Stroke Treatment (PIL-FAST): results
      from the pilot randomised controlled trial.
AB  - BACKGROUND: High blood pressure (BP) during acute stroke is associated with
      poorer stroke outcome. Trials of treatments to lower BP have not resulted in
      improved outcome, but this may be because treatment commenced too late. Emergency
      medical service staff (paramedics) are uniquely placed to administer early
      treatment; however, experience of prehospital randomised controlled trials (RCTs)
      is very limited. METHODS: We conducted a pilot RCT to determine the feasibility
      of a definitive prehospital BP-lowering RCT in acute stroke. Paramedics were
      trained to identify, consent and deliver a first dose of lisinopril or placebo to
      adults with suspected stroke and hypertension while responding to the emergency
      call. Further treatment continued in hospital. Study eligibility, recruitment
      rate, completeness of receipt of study medication and clinical data (eg, BP) were
      collected to inform the design of a definitive RCT. RESULTS: In 14 months, 14
      participants (median age=73 years, median National Institute of Health Stroke
      Scale=4) were recruited and received the prehospital dose of medication. Median
      time from stroke onset (as assessed by paramedic) to treatment was 70 min. Four
      participants completed 7 days of study treatment. Of ambulance transported
      suspected stroke patients, 1% were both study eligible and attended by a PIL-FAST
      paramedic. CONCLUSIONS: It is possible to conduct a paramedic initiated double
      blind RCT of a treatment for acute stroke. However, to perform a definitive RCT
      in a reasonable timescale, a large number of trained paramedics across several
      ambulance services would be needed to recruit the number of patients likely to be
      required. CLINICAL TRIAL REGISTRATION: http://www.clinicaltrials.gov. Unique
      identifier: NCT01066572.

PMID- 24078199
TI  - Surgeons strive hard to break the Da Vinci code.

PMID- 24078200
TI  - A physiological analysis of color vision in batoid elasmobranchs.
AB  - The potential for color vision in elasmobranchs has been studied in detail;
      however, a high degree of variation exists among the group. Evidence for
      ultraviolet (UV) vision is lacking, despite the presence of UV vision in every
      other vertebrate class. An integrative physiological approach was used to
      investigate color and ultraviolet vision in cownose rays and yellow stingrays,
      two batoids that inhabit different spectral environments. Both species had peaks
      in UV, short, medium, and long wavelength spectral regions in dark-, light-, and
      chromatic-adapted electroretinograms. Although no UV cones were found with
      microspectrophotometric analysis, both rays had multiple cone visual pigments
      with lambda max at 470 and 551 nm in cownose rays (Rhinoptera bonasus) and 475,
      533, and 562 nm in yellow stingrays (Urobatis jamaicensis). The same analysis
      demonstrated that both species had rod lambda max at 500 and 499 nm,
      respectively. The lens and cornea of cownose rays maximally transmitted
      wavelengths greater than 350 nm and greater than 376 nm in yellow stingrays.
      These results support the potential for color vision in these species and future
      investigations should reveal the extent to which color discrimination is
      significant in a behavioral context.

PMID- 24078201
TI  - Our ASHRM journey continues: ERM for our patients' safety.
AB  - First and foremost, as your 2013 ASHRM president, I'd like to thank you for all
      of the significant accomplishments you've helped ASHRM attain this year. And I'll
      be forever grateful for your support and making my personal and professional
      dream come true-to serve as your president. Advocating on behalf of all
      healthcare risk managers and furthering the quest of Getting to Zero for our
      patients' safety through Enterprise Risk Management, or ERM, has been an honor,
      because everyone is a risk manager! 

PMID- 24078202
TI  - Growing patient safety through ERM.

PMID- 24078203
TI  - Procedural sedation and implications for quality and risk management.
AB  - A successful procedural sedation program requires a robust institutional policy
      backed by a solid educational program and an administrative structure. Given the
      nature of the services provided, combined with the growth in complexity of both
      patients and procedures, sedation presents a potential liability for both the
      provider and the institution. A sedation program is built with a
      multidisciplinary team of experts representing all stakeholders: healthcare
      providers, risk and quality improvement managers, and facility administration. An
      institutional procedural sedation policy should be based on nationally and state
      recognized practice requirements and guidelines. Clinical care must be supported
      with a robust risk and quality structure built within the program to ensure best
      practice at the point of care. 

PMID- 24078205
TI  - A red-flag-based approach to risk management of EHR-related safety concerns.
AB  - Although electronic health records (EHRs) have a significant potential to improve
      patient safety, EHR-related safety concerns have begun to emerge. Based on 369
      responses to a survey sent to the memberships of the American Society for
      Healthcare Risk Management and the American Health Lawyers Association and
      supplemented by our previous work in EHR-related patient safety, we identified
      the following common EHR-related safety concerns: (1) incorrect patient
      identification; (2) extended EHR unavailability (either planned or unplanned);
      (3) failure to heed a computer-generated warning or alert; (4) system-to-system
      interface errors; (5) failure to identify, find, or use the most recent patient
      data; (6) misunderstandings about time; (7) incorrect item selected from a list
      of items; and (8) open or incomplete orders. In this article, we present a "red
      flag"-based approach that can be used by risk managers to identify potential EHR
      safety concerns in their institutions. An organization that routinely conducts
      EHR-related surveillance activities, such as the ones proposed here, can
      significantly reduce risks associated with EHR implementation and use. 

PMID- 24078204
TI  - An evidence-based toolkit for the development of effective and sustainable root
      cause analysis system safety solutions.
AB  - Root cause analysis (RCA) after adverse events in healthcare is a standard
      practice at many institutions. However, healthcare has failed to see a dramatic
      improvement in patient safety over the last decade. In order to improve the RCA
      process, this study used systems safety science, which is based partly on human
      factors engineering principles and has been applied with success in other high
      risk industries like aviation. A multi-institutional dataset of 334 RCA cases and
      782 solutions was analyzed using qualitative methods. A team of safety science
      experts developed a model of 13 RCA solutions categories through an iterative
      process, using semi-structured interview data from 44 frontline staff members
      from 7 different hospital-based unit types. These categories were placed in a
      model and toolkit to help guide RCA teams in developing sustainable and effective
      solutions to prevent future adverse events. This study was limited by its
      retrospective review of cases and use of interviews rather than clinical
      observations. In conclusion, systems safety principles were used to develop
      guidelines for RCA teams to promote systems-level sustainable and effective
      solutions for adverse events. 

PMID- 24078206
TI  - Enhance patient safety by identifying and minimizing risk exposures affecting
      nurse practitioner practice.
AB  - A study analyzing closed professional liability claims against nurse
      practitioners over a 5-year period was completed by CNA and Nurses Service
      Organization (NSO). Of 200 closed claims, the average total incurred payment per
      claim was $285 645. The study identifies current liability patterns and trends
      and provides risk-control recommendations to enhance patient safety and minimize
      liability exposure. Study results indicate that while the number of nurse
      practitioner claims have been relatively stable over the past 5 years (2007
      2011), the number of claims resulting in very severe indemnity payment have
      increased 19% since 2009. The data also show that many claims develop from a
      failure involving core competencies, such as treatment and care management, and
      medication prescribing. Allegations related to failure to diagnose and delay in
      making a correct diagnosis were found most frequently. The claims demonstrate
      that nurse practitioners are responsible for obtaining and documenting the
      results of appropriate tests, consultations, and overall need for medical
      intervention to meet the patient's medical needs. 

PMID- 24078207
TI  - Determining hospital risk management staffing through analytics.
AB  - This article presents the development of an independent research project to
      gather time data from hospital risk managers in order to establish an objective,
      justifiable means of determining staffing levels recommended to support risk
      management activities and department functions. 

PMID- 24078208
TI  - Case law update. Freudeman v. The Landing at Canton, No. 12-3130 (6th Cir
      December 19, 2012).

PMID- 24078209
TI  - Comparative metabolomics of muscle interstitium fluid in human trapezius myalgia:
      an in vivo microdialysis study.
AB  - PURPOSE: The mechanisms behind trapezius myalgia are unclear. Many hypotheses
      have been presented suggesting an altered metabolism in the muscle. Here, muscle
      microdialysate from healthy and myalgic muscle is analysed using metabolomics.
      Metabolomics analyse a vast number of metabolites, enabling a comprehensive
      explorative screening of the cellular processes in the muscle. METHODS:
      Microdialysate samples were obtained from the shoulder muscle of healthy and
      myalgic subjects that performed a work and stress test. Samples from the baseline
      period and from the recovery period were analysed using gas chromatography-mass
      spectrometry (GC-MS) together with multivariate analysis to detect differences in
      extracellular content of metabolites between groups. Systematic differences in
      metabolites between groups were identified using multivariate analysis and
      orthogonal partial least square discriminate analysis (OPLS-DA). A complementary
      Mann-Whitney U test of group difference in individual metabolites was also
      performed. RESULTS: A large number of metabolites were detected and identified in
      this screening study. At baseline, no systematic differences between groups were
      observed according to the OPLS-DA. However, two metabolites, l-leucine and
      pyroglutamic acid, were significantly more abundant in the myalgic muscle
      compared to the healthy muscle. In the recovery period, systematic difference in
      metabolites between the groups was observed according to the OPLS-DA. The groups
      differed in amino acids, fatty acids and carbohydrates. Myristic acid and
      putrescine were significantly more abundant and beta-d-glucopyranose was
      significantly less abundant in the myalgic muscle. CONCLUSION: This study
      provides important information regarding the metabolite content, thereby
      presenting new clues regarding the pathophysiology of the myalgic muscle.

PMID- 24078210
TI  - BP regulation VI: elevated sympathetic outflow with human aging: hypertensive or
      homeostatic?
AB  - Though conventional wisdom suggests that a rise in blood pressure is a reality of
      advancing age, in fact, it appears that progressive elevation in sympathetic
      activity, not necessarily accompanied by increased blood pressure, is intrinsic
      to cardiovascular aging in humans. The mechanism behind this elevation would seem
      to reside in homeostatic cardiovascular regulation; nonetheless, the balance of
      factors that result in elevated sympathetic outflow with age remains elusive. Age
      related increases in sympathetic nervous outflow cannot be fully explained by
      increases in body mass, body adiposity, or other metabolic factors;
      interrelations among cardiac output, peripheral resistance, and blood pressure
      may not reflect a determinative hemodynamic interrelation but rather parallel
      phenomena; and there is no simple linear relationship between baroreflex control
      and resting levels of sympathetic activity. In contrast to systemic
      relationships, available data suggest that elevated sympathetic outflow may
      derive from the inter-relationship between centrally driven sympatho-excitation
      and a decline in the ability of sympathetic outflow to effect peripheral vascular
      responses. This review aims to integrate the current knowledge of mechanisms
      underlying elevated sympathetic outflow with age. It seeks to synthesize these
      data in the context of proposing that an age-related decline in the ability of
      sympathetic outflow to effect regional vascular responses incites a compensatory
      elevation in resting sympathetic activity to maintain homeostatic balance,
      presumably to maintain adequate control of blood pressure.

PMID- 24078211
TI  - Dark chocolate reduces endothelial dysfunction after successive breath-hold dives
      in cool water.
AB  - OBJECTIVE: The aim of this study is to observe the effects of dark chocolate on
      endothelial function after a series of successive apnea dives in non
      thermoneutral water. METHODS: Twenty breath-hold divers were divided into two
      groups: a control group (8 males and 2 females) and a chocolate group (9 males
      and 1 female). The control group was asked to perform a series of dives to 20 m
      adding up to 20 min in the quiet diving pool of Conflans-Ste-Honorine (Paris,
      France), water temperature was 27  degrees C. The chocolate group performed the
      dives 1 h after ingestion of 30 g of dark chocolate. Flow-mediated dilatation
      (FMD), digital photoplethysmography, nitric oxide (NO), and peroxynitrite ONOO-)
      levels were measured before and after each series of breath-hold dives. RESULTS:
      A significant decrease in FMD was observed in the control group after the dives
      (95.28 +/- 2.9 % of pre-dive values, p < 0.001) while it was increased in the
      chocolate group (104.1 +/- 2.9 % of pre-dive values, p < 0.01). A decrease in the
      NO level was observed in the control group (86.76 +/- 15.57 %, p < 0.05) whereas
      no difference was shown in the chocolate group (98.44 +/- 31.86 %, p > 0.05). No
      differences in digital photoplethysmography and peroxynitrites were observed
      between before and after the dives. CONCLUSION: Antioxidants contained in dark
      chocolate scavenge free radicals produced during breath-hold diving. Ingestion of
      30 g of dark chocolate 1 h before the dive can thus prevent endothelial
      dysfunction which can be observed after a series of breath-hold dives.

PMID- 24078213
TI  - Risk factors and long-term survival in adult patients with primary malignant
      spinal cord astrocytomas.
AB  - Primary intramedullary spinal cord tumors are a rare entity, comprising 4-10 % of
      all spinal cord tumors. The current report presents data on intramedullary spinal
      cord anaplastic astrocytomas and glioblastomas in adults using the national
      surveillance, epidemiology, and end results database (1973-2008), and evaluates
      the impact of demographic and treatment factors on survival. Eighty nine adults
      were evaluated (mean age of 43 years); 49 % of patients had anaplastic
      astrocytoma and 51 % of patients had glioblastoma. 88 % of patients had surgical
      intervention and 85 % of patients had radiotherapy. In univariate analysis, male
      gender (HR = 0.50, CI: 0.29-0.86, P = 0.01), surgical treatment (HR = 0.37, CI:
      0.15-0.93, P = 0.03), and tumor histology (HR = 1.83, CI: 1.06-3.18, P = 0.03)
      were significant predictors of survival. Results remained significant or
      marginally significant after multivariate adjustment analyses. Adjuvant
      radiotherapy and age at diagnosis did not have a significant influence on
      survival. Future prospective studies from collaborative institutions combining
      richer detail in perioperative treatment, radiotherapy dosing, chemotherapy
      treatment, neurologic examinations, functional outcomes, and quality of life
      measures would contribute to more concrete, evidence-based treatment protocols
      for adult patients with primary malignant spinal cord astrocytomas.

PMID- 24078212
TI  - Acute low-load resistance exercise with and without blood flow restriction
      increased protein signalling and number of satellite cells in human skeletal
      muscle.
AB  - PURPOSE: To investigate hypertrophic signalling after a single bout of low-load
      resistance exercise with and without blood flow restriction (BFR). METHODS: Seven
      subjects performed unilateral knee extensions at 30 % of their one repetition
      maximum. The subjects performed five sets to failure with BFR on one leg, and
      then repeated the same amount of work with the other leg without BFR. Biopsies
      were obtained from m. vastus lateralis before and 1, 24 and 48 h after exercise.
      RESULTS: At 1-h post-exercise, phosphorylation of p70S6KThr389 and
      p38MAPKThr180/Tyr182 was elevated in the BFR leg, but not in the free-flow leg.
      Phospho-p70S6KThr389 was elevated three- to fourfold in both legs at 24-h post
      exercise, but back to baseline at 48 h. The number of visible satellite cells
      (SCs) per muscle fibre was increased for all post-exercise time points and in
      both legs (33-53 %). The proportion of SCs with cytoplasmic extensions was
      elevated at 1-h post in the BFR leg and the number of SCs positive for myogenin
      and/or MyoD was increased at 1- and 24-h post-exercise for both legs combined.
      CONCLUSION: Acute low-load resistance exercise with BFR resulted in early (1 h)
      and late (24 h) enhancement of phospho-p70S6KThr389, an early response of
      p38MAPK, and an increased number of SCs per muscle fibre. Enhanced phospho
      p70S6KThr389 at 24-h post-exercise and increases in SC numbers were seen also in
      the free-flow leg. Implications of these findings for the hypertrophic effects of
      fatiguing low-load resistance exercise with and without BFR are discussed.

PMID- 24078214
TI  - Effects of pigment epithelium derived factor (PEDF) on malignant peripheral nerve
      sheath tumours (MPNSTs).
AB  - Neurofibromatosis type 1 (NF1) is an inherited genetic disease affecting 1 in
      3,500 individuals. A prominent feature of NF1 is the formation of benign tumours
      of the peripheral nerve sheath (neurofibromas). However, these can become
      malignant and form highly metastatic malignant peripheral nerve sheath tumours
      (MPNST), which are usually fatal despite aggressive surgery, chemotherapy, and
      radiotherapy. Recent studies have shown that pigment epithelium-derived factor
      (PEDF) can induce differentiation and inhibit angiogenesis in several kinds of
      tumours. The present study was designed to determine the in vitro and in vivo
      effects of PEDF on MPNST angiogenesis and tumour growth. PEDF inhibited
      proliferation and augmented apoptosis in S462 MPNST cells after 48 h of treatment
      in culture. In xenografts of S462 MPNST cells in athymic nude mice, PEDF
      suppressed MPNST tumour burden, due mainly to inhibition of angiogenesis. These
      results demonstrate for the first time inhibitory effects of PEDF on the growth
      of human MPNST via induction of anti-angiogenesis and apoptosis. Our results
      suggest that PEDF could be a novel approach for future therapeutic purposes
      against MPNST.

PMID- 24078215
TI  - Temozolomide and irradiation combined treatment-induced Nrf2  activation
      increases chemoradiation sensitivity in human  glioblastoma cells.
AB  - Resistance to chemoradiotherapy is a major obstacle to successful treatment of
      glioblastoma. Recently, the role of NF-E2-related factor 2 (Nrf2) in enhancing
      chemoradiation sensitivity has been reported in several types of cancers. Here,
      we investigated whether temozolomide (TMZ) and irradiation (IR) combined
      treatment induced Nrf2 activation in human glioblastoma cells. And we further
      performed a preliminary study about the effect of Nrf2 on chemoradiation
      sensitivity. Immunohistochemical staining for Nrf2 in paired clinical specimens
      showed that TMZ and IR combined treatment increased the expression and nuclear
      localization of Nrf2 in human glioblastoma tissues. Moreover, we found nuclear
      Nrf2 expression in the glioblastoma tissues obtained from the patients undergoing
      TMZ and IR combined treatment was associated with the time to tumor recurrence.
      In vitro, we further verified these findings. First, we detected increased
      nuclear localization of Nrf2 following treatment with TMZ+IR in human
      glioblastoma cell lines. Second, we demonstrated TMZ+IR increased the levels of
      Nrf2 protein in both nuclear and cytoplasmic fractions of U251 cells and induced
      Nrf2 target genes expression. Finally, downregulating Nrf2 expression increased
      TMZ+IR-induced cell death in the U251 cells. These findings suggest TMZ+IR
      combined treatment induces Nrf2 activation in human glioblastoma cells. The
      activation of Nrf2 may be associate with enhancing chemoradiation sensitivity in
      human glioblastoma cell. Blocking Nrf2 activation may be a promising method
      enhancing chemoradiation sensitivity of glioblastoma cells.

PMID- 24078216
TI  - Physiological changes to the swallowing mechanism following (chemo)radiotherapy
      for head and neck cancer: a systematic review.
AB  - Emerging research suggests that preventative swallowing rehabilitation,
      undertaken before or during (chemo)radiotherapy ([C]RT), can significantly
      improve early swallowing outcomes for head and neck cancer (HNC) patients.
      However, these treatment protocols are highly variable. Determining specific
      physiological swallowing parameters that are most likely to be impacted post
      (C)RT would assist in refining clear targets for preventative rehabilitation.
      Therefore, this systematic review (1) examined the frequency and prevalence of
      physiological swallowing deficits observed post-(C)RT for HNC, and (2) determined
      the patterns of prevalence of these key physiological deficits over time post
      treatment. Online databases were searched for relevant papers published between
      January 1998 and March 2013. A total of 153 papers were identified and appraised
      for methodological quality and suitability based on exclusionary criteria.
      Ultimately, 19 publications met the study's inclusion criteria. Collation of
      reported prevalence of physiological swallowing deficits revealed reduced
      laryngeal excursion, base-of-tongue (BOT) dysfunction, reduced pharyngeal
      contraction, and impaired epiglottic movement as most frequently reported. BOT
      dysfunction and impaired epiglottic movement showed a collective prevalence of
      over 75 % in the majority of patient cohorts, whilst reduced laryngeal elevation
      and pharyngeal contraction had a prevalence of over 50 %. Subanalysis suggested a
      trend that the prevalence of these key deficits is dynamic although persistent
      over time. These findings can be used by clinicians to inform preventative
      intervention and support the use of specific, evidence-based therapy tasks
      explicitly selected to target the highly prevalent deficits post-(C)RT for HNC.

PMID- 24078217
TI  - Convergence of goals: phylogenetical, morphological, and physiological
      characterization of tolerance to drought stress in tall fescue (Festuca
      arundinacea Schreb.).
AB  - The aim of this study is to find Iranian tall fescue accessions that tolerate
      drought stress and investigation on phylogenetical, morphological, and
      physiological characterization of them. For this propose, inter-simple sequence
      repeats (ISSR) markers were used to examine the genetic variability of accessions
      from different provinces of Iran. Of 21 primers, 20 primers generated highly
      reproducible fragments. Using these primers, 390 discernible DNA fragments were
      produced with 367 (93.95 %) being polymorphic. The polymorphic information
      content (PIC) values ranged from 0.948 to 0.976, with a mean PIC value of 0.969.
      Probability identity (PI) and discriminating power (D = 1-PI) among the primers
      ranged from 0.001 to 0.004 and 0.998 to 0.995, respectively. A binary qualitative
      data matrix was constructed. Data analyses were performed using the NTSYS
      software and the similarity values were used to generate a dendrogram via UPGMA.
      To study the drought stress, plants were irrigated at 25 % FC condition for three
      times. Fresh leaves were collected to measure physiological characters including:
      superoxide dismutase, catalase, and peroxidase activities and proline and total
      chlorophyll content at two times, before and after stress application. Relative
      water content, fresh and dry weight ratio, survival percentage, and visual
      quality were evaluated after stress. Morphological and physiological characters
      were assessed in order to classify accessions as either tolerant or sensitive
      using Ward's method of Hierarchical cluster analysis in SPSS software. The
      results of present study demonstrated that the ISSR markers are useful for
      studying tall fescue genetic diversity. Convergence of morphological and
      physiological characterizations during drought stress and phylogenetic
      relationship results showed that accessions can be grouped into four clusters;
      drought-tolerant accessions that collected from west of Iran, drought-tolerant
      accessions collected from northwest of Iran, drought semi-tolerant accessions
      collected from center of Iran, and drought-sensitive accessions collected from
      north of Iran. Data presented could be used to classify the tall fescue
      accessions based on suitability of cultivation in the regions studied or the
      regions with the similar environmental condition.

PMID- 24078218
TI  - Cytoprotection by the NO-donor SNAP against ischemia/reoxygenation injury in
      mouse embryonic stem cell-derived cardiomyocytes.
AB  - Embryonic stem cell (ESC)-derived cardiomyocytes are a promising cell source for
      the screening for potential cytoprotective molecules against ischemia/reperfusion
      injury, however, little is known on their behavior in hypoxia/reoxygenation
      conditions. Here we tested the cytoprotective effect of the NO-donor SNAP and its
      downstream cellular pathway. Mouse ESC-derived cardiomyocytes were subjected to
      150-min simulated ischemia (SI) followed by 120-min reoxygenation or
      corresponding non-ischemic conditions. The following treatments were applied
      during SI or normoxia: the NO-donor S-Nitroso-N-acetyl-D,L-penicillamine (SNAP),
      the protein kinase G (PKG) inhibitor, the KATP channel blocker glibenclamide, the
      particulate guanylate cyclase activator brain type natriuretic peptide (BNP), and
      a non-specific NO synthase inhibitor (N-Nitro-L-arginine, L-NNA) alone or in
      different combinations. Viability of cells was assayed by propidium iodide
      staining. SNAP attenuated SI-induced cell death in a concentration-dependent
      manner, and this protection was attenuated by inhibition of either PKG or KATP
      channels. However, SI-induced cell death was not affected by BNP or by L-NNA. We
      conclude that SNAP protects mESC-derived cardiomyocytes against SI/R injury and
      that soluble guanylate-cyclase, PKG, and KATP channels play a role in the
      downstream pathway of SNAP-induced cytoprotection. The present mESC-derived
      cardiomyocyte based screening platform is a useful tool for discovery of
      cytoprotective molecules.

PMID- 24078220
TI  - Isolation and functional characterization of a novel seed-specific promoter
      region from peanut.
AB  - The importance of using tissue-specific promoters in the genetic transformation
      of plants has been emphasized increasingly. Here, we report the isolation of a
      novel seed-specific promoter region from peanut and its validation in Arabidopsis
      and tobacco seeds. The reported promoter region referred to as groundnut seed
      promoter (GSP) confers seed-specific expression in heterologous systems, which
      include putative promoter regions of the peanut (Arachis hypogaea L.) gene
      8A4R19G1. This region was isolated, sequenced, and characterized using gel shift
      assays. Tobacco transgenics obtained using binary vectors carrying uidA reporter
      gene driven by GSP and/or cauliflower mosaic virus 35S promoters were confirmed
      through polymerase chain reaction (PCR), RT-PCR, and computational analysis of
      motifs which revealed the presence of TATA, CAAT boxes, and ATG signals. This
      seed-specific promoter region successfully targeted the reporter uidA gene to
      seed tissues in both Arabidopsis and tobacco model systems, where its expression
      was confirmed by histochemical analysis of the transgenic seeds. This promoter
      region is routinely being used in the genetic engineering studies in legumes
      aimed at targeting novel transgenes to the seeds, especially those involved in
      micronutrient enhancement, fungal resistance, and molecular pharming.

PMID- 24078219
TI  - Design and optimization of SPR-based binding assay for evaluation and screening
      of MITF-E-box binding inhibitor.
AB  - Melanin synthesis is a complex phenomenon which involves about 192 known gene
      products. Among them, MITF is a key transcription factor for tyrosinase, Trp1 and
      Trp2 proteins, which are essential for melanin biosynthesis. Thus, intervening
      inhibitor for the MITF-E-box complex formation can downregulate melanin
      synthesis. The focus of the present study is to develop a surface plasmon
      resonance-based system to screen the MITF-E-box complex inhibitor. The
      standardization of the MITF and E-box binding assay was calibrated for kinetics
      and specificity, in the presence of a pre-incubated 22 mer sequence containing
      mutated E-box (CTTGAG) along MITF. The binding assay with C17 was optimized and
      the steady-state kinetics was evaluated. C17 was identified as inhibitor to MITF
      E-box, by virtual screening followed by in vitro assessment and EMSA assay. The
      k(a) and k(d) were found to be 5.5 9 103 M-1 s-1 and 0.0014 s-1, respectively,
      while the steady-state association constant (K(A)) was 3.928 9 106 M-1. The
      resonance variations after inhibition were quantified and analyzed to develop the
      standard method for screening of microphthalmia transcription factor-E-box
      binding inhibitor.

PMID- 24078221
TI  - n-3 LC-PUFA deposition efficiency and appetite-regulating hormones are modulated
      by the dietary lipid source during rainbow trout grow-out and finishing periods.
AB  - Largely attributable to concerns surrounding sustainability, the utilisation of
      omega-3 long-chain polyunsaturated fatty acid-rich (n-3 LC-PUFA) fish oils in
      aquafeeds for farmed fish species is an increasingly concerning issue. Therefore,
      strategies to maximise the deposition efficiency of these key health beneficial
      fatty acids are being investigated. The present study examined the effects of
      four vegetable-based dietary lipid sources (linseed, olive, palm and sunflower
      oil) on the deposition efficiency of n-3 LC-PUFA and the circulating blood plasma
      concentrations of the appetite-regulating hormones, leptin and ghrelin, during
      the grow-out and finishing phases in rainbow trout culture. Minimal detrimental
      effects were noted in fish performance; however, major modifications were
      apparent in tissue fatty acid compositions, which generally reflected that of the
      diet. These modifications diminished somewhat following the fish oil finishing
      phase, but longer-lasting effects remained evident. The fatty acid composition of
      the alternative oils was demonstrated to have a modulatory effect on the
      deposition efficiency of n-3 LC-PUFA and on the key endocrine hormones involved
      in appetite regulation, growth and feed intake during both the grow-out and
      finishing phases. In particular, n-6 PUFA (sunflower oil diet) appeared to
      'spare' the catabolism of n-3 LC-PUFA and, as such, resulted in the highest
      retention of these fatty acids, ultimately highlighting new nutritional
      approaches to maximise the maintenance of the qualitative benefits of fish oils
      when they are used in feeds for aquaculture species.

PMID- 24078222
TI  - In vitro exposure to copper influences lipid metabolism in hepatocytes from grass
      carp (Ctenopharyngodon idellus).
AB  - In the present study, three different copper (Cu) concentrations (control, 10 and
      100 lM, respectively) and three incubation times (24, 48 and 96 h) were chosen to
      assess in vitro effect of Cu on lipid metabolism in hepatocytes of grass carp
      Ctenopharyngodon idellus. Increased glucose 6-phosphate dehydrogenase, 6
      phosphogluconate dehydrogenase and carnitine palmitoyltransferase I activities
      were observed in hepatocytes with increasing Cu concentration and exposure
      duration. Cu decreased mRNA levels of several lipogenic and lipolytic genes at 24
      h. However, at 48 h, Cu down-regulated the process of lipogenesis but up
      regulated that of lipolysis. The Cudriven up-regulation of lipolytic genes was
      maintained after 96 h and accompanied by a decreased intracellular triglyceride
      accumulation, while no effect on lipogenic genes was shown. Thus, 96-h Cu
      exposure induced lipid depletion, possibly due to the upregulation of lipolysis.
      Although in this process, lipogenesis might be up-regulated, it was not enough to
      compensate lipid consumption. Our study represents the first approach to
      concentration- and time-dependent in vitro effects of Cu on lipid metabolism of
      fish hepatocytes and provides new insights into Cu toxicity in fish at both
      enzymatic and molecular levels.

PMID- 24078223
TI  - Economic evaluation of Cardio inCode(r), a clinical-genetic function for coronary
      heart disease risk assessment.
AB  - BACKGROUND: A clinical-genetic function (Cardio inCode(r)) was generated using
      genetic variants associated with coronary heart disease (CHD), but not with
      classical CHD risk factors, to achieve a more precise estimation of the CHD risk
      of individuals by incorporating genetics into risk equations [Framingham and
      REGICOR (Registre Gironi del Cor)]. OBJECTIVE: The objective of this study was to
      conduct an economic analysis of the CHD risk assessment with Cardio inCode(r),
      which incorporates the patient's genetic risk into the functions of REGICOR and
      Framingham, compared with the standard method (using only the functions).
      METHODS: A Markov model was developed with seven states of health (low CHD risk,
      moderate CHD risk, high CHD risk, CHD event, recurrent CHD, chronic CHD, and
      death). The reclassification of CHD risk derived from genetic information and
      transition probabilities between states was obtained from a validation study
      conducted in cohorts of REGICOR (Spain) and Framingham (USA). It was assumed that
      patients classified as at moderate risk by the standard method were the best
      candidates to test the risk reclassification with Cardio inCode(r). The utilities
      and costs (?; year 2011 values) of Markov states were obtained from the
      literature and Spanish sources. The analysis was performed from the perspective
      of the Spanish National Health System, for a life expectancy of 82 years in
      Spain. An annual discount rate of 3.5 % for costs and benefits was applied.
      RESULTS: For a Cardio inCode(r) price of ?400, the cost per QALY gained compared
      with the standard method [incremental cost-effectiveness ratio (ICER)] would be
      ?12,969 and ?21,385 in REGICOR and Framingham cohorts, respectively. The
      threshold price of Cardio inCode(r) to reach the ICER threshold generally
      accepted in Spain (?30,000/QALY) would range between ?668 and ?836. The greatest
      benefit occurred in the subgroup of patients with moderate-high risk, with a high
      risk reclassification of 22.8 % and 12 % of patients and an ICER of ?1,652/QALY
      and ?5,884/QALY in the REGICOR and Framingham cohorts, respectively. Sensitivity
      analyses confirmed the stability of the study results. CONCLUSIONS: Cardio
      inCode(r) is a cost-effective risk score option in CHD risk assessment compared
      with the standard method.

PMID- 24078226
TI  - Haemagglutinin and nucleoprotein replicon particle vaccination of swine protects
      against the pandemic H1N1 2009 virus.
AB  - The recent emergence of the pandemic H1N1 (pH1N1) and H3N2 variant influenza A
      viruses (IAV) in 2009 and 2011-2012, respectively, highlight the zoonotic
      potential of influenza viruses and the need for vaccines capable of eliciting
      heterosubtypic protection. In these studies, single-cycle, propagation-defective
      replicon particle (RP) vaccines expressing IAV haemagglutinin (HA) and
      nucleoprotein (NP) genes were constructed and efficacy was evaluated in
      homologous and heterologous pig challenge studies with the pH1N1 2009 influenza
      virus (A/California/04/2009). Homologous HA RP vaccination eliminated virus
      shedding and decreased pulmonary pathology in pigs following pH1N1 2009
      challenge. An RP vaccine expressing an H3N2-derived NP gene was able to decrease
      nasal shedding and viral load following heterosubtypic pH1N1 2009 challenge in
      pigs. These studies indicate that although homologous vaccination of swine
      remains the most effective means of preventing IAV infection, other vaccine
      alternatives do offer a level of heterosubtypic protection, and should continue
      to be evaluated for their ability to provide broader protection. 

PMID- 24078227
TI  - Trochlear wedge migration: an unusual complication following patellar luxation
      surgery.

PMID- 24078228
TI  - A novel zoometric index for assessing body composition in adult rabbits.
AB  - Obesity is an emerging problem in domesticated rabbits, and an easy-to-use
      measure of adipose tissue mass is needed. The current study aimed to develop a
      zoometric ratio, capable of estimating body condition in rabbits. Body weight
      (BW), body condition score (BCS), and zoometric measures (distal forelimb length,
      DFL; vertebral length, VL were measured in 150 pet rabbits. Zoometric formulae
      were created, combining BW with a zoometric measure, and these were tested for
      their ability to predict adipose tissue mass judged by BCS. Seventy-five (50 per
      cent) of the rabbits were in ideal condition (BCS 2.5-3.5), 52 (35 per cent) were
      overweight (BCS>3.5), and 23 (15 per cent) were underweight (BCS<2.5). Median
      (range) DFL and VL measurements were 12.1 (8.8-16.4 cm) and 34.0 (26.5-50.5 cm),
      respectively. In rabbits of medium breed size, the BW/DFL ratio was most strongly
      associated with BCS (Kendall's tau 0.80, P<0.001). Using BW/DFL limits for
      optimum body condition (eg, minimum 0.16; maximum 0.21), all underweight and
      overweight rabbits were correctly classified, while only 2/61 (3 per cent)
      rabbits with an optimum BCS were incorrectly classified as overweight. This study
      provides preliminary evidence that the BW/DFL might be a useful indirect measure
      of adipose tissue mass in rabbits of medium breed size. 

PMID- 24078230
TI  - Body weight and risk of early death.

PMID- 24078229
TI  - Aryl hydrocarbon receptor in breast cancer-a newly defined prognostic marker.
AB  - Aryl hydrocarbon receptor (AhR) has been reported to exert various anticancer
      effects upon breast carcinoma cells in vitro but its details have remained
      largely unknown. Therefore, we first examined the AhR status in 90 invasive
      ductal carcinoma patients using immunohistochemistry. We then performed in vitro
      studies including wound healing assay, invasion assay, and matrix
      metalloproteinase (MMP) protein array in order to further elucidate the roles of
      AhR signaling in breast carcinoma. The status of AhR immunoreactivity was
      inversely correlated with histological grade (P = 0.0135) and Ki-67 labeling
      index (LI; P = 0.0087) of the patients. In addition, results of both uni- and
      multivariate analyses revealed that AhR in carcinoma cells turned out an
      independent prognostic factor with a protective relative risk (P = 0.0179). An
      administration of 10 nM 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD), a ligand of
      AhR, significantly decreased Ki-67 LI in an AhR-dependent fashion in MCF-7, T47D,
      ZR75-1, and MDA-MB-231. Wound healing and invasion assays performed in T47D and
      ZR75-1 further demonstrated that 10 nM TCDD inhibited estrogen-induced migration
      and invasion of cells. MMP proteins associated with AhR in breast carcinoma cells
      were also firstly identified. These results demonstrated that AhR in breast
      carcinoma cells is considered a newly defined histological prognostic parameter
      of the breast cancer patients and effects of AhR activation on proliferation and
      MMPs expression may be related to the relatively good clinical outcome of AhR
      positive breast cancer patients.

PMID- 24078231
TI  - Does being overweight really reduce mortality?

PMID- 24078232
TI  - The metabolically healthy overweight and obese and their impact on all-cause
      mortality.

PMID- 24078233
TI  - Identification of quantitative trait loci associated with resistance to viral
      haemorrhagic septicaemia (VHS) in turbot (Scophthalmus maximus ): a comparison
      between bacterium, parasite and virus diseases.
AB  - One of the main objectives of genetic breeding programs in turbot industry is to
      reduce disease-related mortality. In the present study, a genome scan to detect
      quantitative trait loci (QTL) affecting resistance and survival to viral
      haemorrhagic septicaemia (VHS) was carried out. Three full-sib families with
      approximately 90 individuals each were genotyped and evaluated by linear
      regression and maximum likelihood approaches. In addition, a comparison between
      QTL detected for resistance and survival time to other important bacterial and
      parasite diseases affecting turbot (furunculosis and scuticociliatosis) was also
      carried out. Finally, the relationship between QTL affecting resistance/survival
      time to the virus and growth-related QTL was also evaluated. Several genomic
      regions controlling resistance and survival time to VHS were detected. Also
      significant associations between the evaluated traits and genotypes at particular
      markers were identified, explaining up to 14 % of the phenotypic variance.
      Several genomic regions controlling general and specific resistance to different
      diseases in turbot were detected. A preliminary gene mining approach identified
      candidate genes related to general or specific immunity. This information will be
      valuable to develop marker-assisted selection programs and to discover candidate
      genes related to disease resistance to improve turbot production.

PMID- 24078234
TI  - Minimally invasive endovascular and biliary treatments of children with acute
      hepatic artery thrombosis following liver transplantation.
AB  - Hepatic artery thrombosis is a major problem after pediatric liver
      transplantation. Ischemia caused by hepatic artery thrombosis results in severe
      biliary and parenchymal damage and is associated with high rates of graft loss
      and mortality. We present a case-based pictorial essay to illustrate the role of
      minimally invasive treatment in the prompt management of acute hepatic artery
      thrombosis, and the associated biliary complications.

PMID- 24078235
TI  - Amelioration of acidic soil using various renewable waste resources.
AB  - In this study, improvement of acidic soil with respect to soil pH and
      exchangeable cations was attempted for sample with an initial pH of approximately
      5. Acidic soil was amended with various waste resources in the range of 1 to 5
      wt.% including waste oyster shells (WOS), calcined oyster shells (COS), Class C
      fly ash (FA), and cement kiln dust (CKD) to improve soil pH and exchangeable
      cations. Upon treatment, the soil pH was monitored for periods up to 3 months.
      The exchangeable cations were measured after 1 month of curing. After a curing
      period of 1 month, a maize growth experiment was conducted with selected-treated
      samples to evaluate the effectiveness of treatment. The treatment results
      indicate that in order to increase the soil pH to a value of 7, 1 wt.% of WOS, 3
      wt.% of FA, and 1 wt.% of CKD are required. In the case of COS, 1 wt.% was more
      than enough to increase the soil pH value to 7 because of COS's strong
      alkalinity. Moreover, the soil pH increases after a curing period of 7 days and
      remains virtually unchanged thereafter up to 1 month of curing. Upon treatment,
      the summation of cations (Ca, Mg, K, and Na) significantly increased. The growth
      of maize is superior in the treated samples rather than the untreated one,
      indicating that the amelioration of acidic soil is beneficial to plant growth,
      since soil pH was improved and nutrients were replenished.

PMID- 24078236
TI  - The integrated biomarker response revisited: optimization to avoid misuse.
AB  - The growing need to evaluate the quality of aquatic ecosystems led to the
      development of numerous monitoring tools. Among them, the development of
      biomarker-based procedures, that combine precocity and relevance, is recommended.
      However, multi-biomarker approaches are often hard to interpret, and produce
      results that are not easy to integrate in the environmental policies framework.
      Integrative index have been developed, and one of the most used is the integrated
      biomarker response (IBR). However, an analysis of available literature
      demonstrated that the IBR suffers from a frequent misuse and a bias in its
      calculation. Then, we propose here a new calculation method based on both a more
      simple formula and a permutation procedure. Together, these improvements should
      rightly avoid the misuse and bias that were recorded. Additionally, a case study
      illustrates how the new procedure enabled to perform a reliable classification of
      site along a pollution gradient based on biomarker responses used in the IBR
      calculations.

PMID- 24078237
TI  - Speciation of metals in contaminated sediments from Oskarshamn Harbor,
      Oskarshamn, Sweden.
AB  - Bottom sediments in coastal regions have been considered the ultimate sink for a
      number of contaminants, e.g., toxic metals. In this current study, speciation of
      metals in contaminated sediments of Oskarshamn harbor in the southeast of Sweden
      was performed in order to evaluate metal contents and their potential mobility
      and bioavailability. Sediment speciation was carried out by the sequential
      extraction BCR procedure for As, Cd, Cr, Cu, Hg, Ni, Pb, and Zn and the
      exchangeable (F1), reducible (F2), oxidizable (F3), and residual (R)
      fractionswere determined. The results have shown that Zn and Cd were highly
      associated with the exchangeable fraction (F1) with 42-58 % and 43-46 %,
      respectively, of their total concentrations in the mobile phase. The assessment
      of sediment contamination on the basis of quality guidelines established by the
      Swedish Environmental Protection Agency (SEPA) and the Italian Ministry of
      Environment (Venice protocol for dredged sediments) has shown that sediments from
      Oskarshamn harbor are highly contaminated with toxic metals, especially Cu, Cd,
      Pb, Hg, As, and Zn posing potential ecological risks. Therefore, it is of crucial
      importance the implementation of adequate strategies to tackle contaminated
      sediments in coastal regions all over the world.

PMID- 24078238
TI  - Baseline resolution of isomers by traveling wave ion mobility mass spectrometry:
      investigating the effects of polarizable drift gases and ionic charge
      distribution.
AB  - We have studied the behavior of isomers and analogues by traveling wave ion
      mobility mass spectrometry (TWIM-MS) using drift-gases with varying masses and
      polarizabilities. Despite the reduced length of the cell (18 cm), a pair of
      constitutional isomers, N-butylaniline and para-butylaniline, with theoretical
      collision cross-section values in helium (OmegaHe ) differing by as little as 1.2
      A(2) (1.5%) but possessing contrasting charge distribution, showed baseline peak
      to-peak resolution (Rp-p ) for their protonated molecules, using carbon dioxide
      (CO2), nitrous oxide (N2O) and ethene (C2H4 ) as the TWIM drift-gas. Near
      baseline Rp-p was also obtained in CO2 for a group of protonated haloanilines
      (para-chloroaniline, para-bromoaniline and para-iodoaniline) which display
      contrasting masses and theoretical OmegaHe , which differ by as much as 15.7 A(2)
      (19.5%) but similar charge distributions. The deprotonated isomeric pair of trans
      oleic acid and cis-oleic acid possessing nearly identical theoretical OmegaHe and
      OmegaN2 as well as similar charge distributions, remained unresolved.
      Interestingly, an inversion of drift-times were observed for the 1,3
      dialkylimidazolium ions when comparing He, N2 and N2O. Using density functional
      theory as a means of examining the ions electronic structure, and He and N2-based
      trajectory method algorithm, we discuss the effect of the long-range charge
      induced dipole attractive and short-range Van der Waals forces involved in the
      TWIM separation in drift-gases of differing polarizabilities. We therefore
      propose that examining the electronic structure of the ions under investigation
      may potentially indicate whether the use of more polarizable drift-gases could
      improve separation and the overall success of TWIM-MS analysis.

PMID- 24078239
TI  - MALDI ionization mechanisms: the coupled photophysical and chemical dynamics
      model correctly predicts 'temperature'-selected spectra.
AB  - A number of possible ultraviolet MALDI ionization mechanisms based on different
      fundamental phenomena have been proposed. Recently, it has been argued, based on
      'temperature'-selected spectra, that photoionization models should be rejected in
      favor of thermal ones. Here, one non-thermal photoionization model, the coupled
      photophysical and chemical dynamics model, is shown to be fully consistent with
      the data.

PMID- 24078240
TI  - Boron forms unexpected glycopeptide derivatives during MALDI-MS experiment.

PMID- 24078241
TI  - H2O loss in the fragmentation of deprotonated N-o-tolylamides in tandem mass
      spectrometry.

PMID- 24078242
TI  - Distinguishing two isomeric mephedrone substitutes with selective reagent
      ionisation mass spectrometry (SRI-MS).
AB  - The isomers 4-methylethcathinone and N-ethylbuphedrone are substitutes for the
      recently banned drug mephedrone. We find that with conventional proton transfer
      reaction mass spectrometry (PTR-MS), it is not possible to distinguish between
      these two isomers, because essentially for both substances, only the protonated
      molecules are observed at a mass-to-charge ratio of 192 (C12 H18NO(+)). However,
      when utilising an advanced PTR-MS instrument that allows us to switch the reagent
      ions (selective reagent ionisation) from H3O(+) (which is commonly used in PTR
      MS) to NO(+), O2(+) and Kr(+), characteristic product (fragment) ions are
      detected: C4H10N(+) (72 Da) for 4-methylethcathinone and C5 H12N(+) (86 Da) for N
      ethylbuphedrone; thus, selective reagent ionisation MS proves to be a powerful
      tool for fast detection and identification of these compounds.

PMID- 24078243
TI  - Revealing the metabolic sites of atazanavir in human by parallel administrations
      of D-atazanavir analogs.
AB  - Atazanavir (Reyataz((r))) is an important member of the HIV protease inhibitor
      class. Because of the complexity of its chemical structure, metabolite
      identification and structural elucidation face serious challenges. So far, only
      seven non-conjugated metabolites in human plasma have been reported, and their
      structural elucidation is not complete, especially for the major metabolites
      produced by oxidations. To probe the exact sites of metabolism and to elucidate
      the relationship among in vivo metabolites of atazanavir, we designed and
      performed two sets of experiments. The first set of experiments was to determine
      atazanavir metabolites in human plasma by LC-MS, from which more than a dozen
      metabolites were discovered, including seven new ones that have not been
      reported. The second set involved deuterium labeling on potential metabolic sites
      to generate D-atazanavir analogs. D-atazanavir analogs were dosed to human in
      parallel with atazanavir. Metabolites of D-atazanavir were identified by the same
      LC-MS method, and the results were compared with those of atazanavir. A
      metabolite structure can be readily elucidated by comparing the results of the
      analogs and the pathway by which the metabolite is formed can be proposed with
      confidence. Experimental results demonstrated that oxidation is the most common
      metabolic pathway of atazanavir, resulting in the formation of six metabolites of
      monooxidation (M1, M2, M7, M8, M13, and M14) and four of dioxidation (M15, M16,
      M17, and M18). The second metabolic pathway is hydrolysis, and the third is N
      dealkylation. Metabolites produced by hydrolysis include M3, M4, and M19.
      Metabolites formed by N-dealkylation are M5, M6a, and M6b.

PMID- 24078244
TI  - Novel and cost-effective 6-plex isobaric tagging reagent, DiART, is effective for
      identification and relative quantification of complex protein mixtures using PQD
      fragmentation.
AB  - Deuterium isobaric Amine Reactive Tag (DiART) reagents facilitate relative
      quantification during proteomic analysis in a functionally similar manner to
      commercially available isobaric tag for relative and absolute quantitation
      (iTRAQ) and tandem mass tag (TMT) reagents. In contrast to iTRAQ and TMT, DiART
      reagents incorporate deuterium isotopes which significantly reduce the number of
      required synthesis steps and hence have potential to significantly reduce reagent
      production cost. We examined the capability of DiART for performing quantitative
      proteomic experiments using a linear ion-trap mass spectrometer with Pulsed Q
      Dissociation (PQD) fragmentation. Using a synthetic peptide tagged with DiART
      reagent, we observed a precise mass shift of 144.79 Da on the triply charged
      precursor ion, which shows complete derivatization of the N-terminus and epsilon
      amino group of lysine. A DiART tagged tryptic digest of bovine serum albumin
      showed a sequence coverage of 57.99% which was very comparable to that showed by
      iTRAQ, 54.77%. Furthermore, a ten protein mixture tagged with DiART reagents and
      mixed in 1:1:1:1:1:1 exhibited < 15% error, whereas a linear trend (slope of
      1.085) was observed when tagged proteins were mixed in the ratio 2:1:2:4:10:14
      and plotted against theoretical ratios. Finally, when complex cell-wall protein
      mixtures from the model fungus A. nidulans were tagged with DiART reagents and
      mixed in different ratios, they exhibited similar trends. We conclude that DiART
      reagents are capable of performing quantitative proteomic experiments using PQD
      on a linear ion trap mass spectrometer.

PMID- 24078245
TI  - Document authentication at molecular levels using desorption atmospheric pressure
      chemical ionization mass spectrometry imaging.
AB  - Molecular images of documents were obtained by sequentially scanning the surface
      of the document using desorption atmospheric pressure chemical ionization mass
      spectrometry (DAPCI-MS), which was operated in either a gasless, solvent-free or
      methanol vapor-assisted mode. The decay process of the ink used for handwriting
      was monitored by following the signal intensities recorded by DAPCI-MS.
      Handwritings made using four types of inks on four kinds of paper surfaces were
      tested. By studying the dynamic decay of the inks, DAPCI-MS imaging
      differentiated a 10-min old from two 4 h old samples. Non-destructive forensic
      analysis of forged signatures either handwritten or computer-assisted was
      achieved according to the difference of the contour in DAPCI images, which was
      attributed to the strength personalized by different writers. Distinction of the
      order of writing/stamping on documents and detection of illegal printings were
      accomplished with a spatial resolution of about 140 um. A Matlab(r) written
      program was developed to facilitate the visualization of the similarity between
      signature images obtained by DAPCI-MS. The experimental results show that DAPCI
      MS imaging provides rich information at the molecular level and thus can be used
      for the reliable document analysis in forensic applications.

PMID- 24078246
TI  - LC-MS analysis of estradiol in human serum and endometrial tissue: Comparison of
      electrospray ionization, atmospheric pressure chemical ionization and atmospheric
      pressure photoionization.
AB  - Accurate measurement of estradiol (E2) is important in clinical diagnostics and
      research. High sensitivity methods are critical for specimens with E2
      concentrations at low picomolar levels, such as serum of men, postmenopausal
      women and children. Achieving the required assay performance with LC-MS is
      challenging due to the non-polar structure and low proton affinity of E2.
      Previous studies suggest that ionization has a major role for the performance of
      E2 measurement, but comparisons of different ionization techniques for the
      analysis of clinical samples are not available. In this study, female serum and
      endometrium tissue samples were used to compare electrospray ionization (ESI),
      atmospheric pressure chemical ionization (APCI) and atmospheric pressure
      photoionization (APPI) in both polarities. APPI was found to have the most
      potential for E2 analysis, with a quantification limit of 1 fmol on-column. APCI
      and ESI could be employed in negative polarity, although being slightly less
      sensitive than APPI. In the presence of biological background, ESI was found to
      be highly susceptible to ion suppression, while APCI and APPI were largely
      unaffected by the sample matrix. Irrespective of the ionization technique,
      background interferences were observed when using the multiple reaction
      monitoring transitions commonly employed for E2 (m/z 271 > 159; m/z 255 > 145).
      These unidentified interferences were most severe in serum samples, varied in
      intensity between ionization techniques and required efficient chromatographic
      separation in order to achieve specificity for E2.

PMID- 24078247
TI  - Trapping mode dipolar DC collisional activation in the RF-only ion guide of a
      linear ion trap/time-of-flight instrument for gaseous bio-ion declustering.
AB  - The application of dipolar direct current (DDC) to the radio frequency-only ion
      guide (Q0) of a hybrid quadrupole/time-of-flight mass spectrometer for collision
      induced declustering of large bio-ions is described. As a broadband technique,
      ion trap DDC collisional activation (CA) is employed to decluster ions
      simultaneously over a relatively broad mass-to-charge (m/z) range. Declustering
      DDC CA can yield significantly narrower peaks relative to those observed in the
      absence of declustering methods, depending upon the extent of noncovalent
      adduction associated with the ions, and can also be used in conjunction with
      other methods, such as nozzle-skimmer CA. The key experimental variables in the
      DDC experiment are the DDC voltage (VDDC), VRF , and the time over which VDDC is
      applied. The VDDC/VRF ratio is key to the extent to which ion temperatures are
      elevated and also influences the upper m/z limit for ion storage. The VDDC/VRF
      ratio affects ion temperatures and the upper m/z limit in opposing directions.
      That is, as the ratio increases, the ion temperature also increases, whereas the
      upper m/z storage limit decreases. However, for a given VDDC /VRF ratio, the
      upper m/z storage limit can be increased by increasing VRF, at the expense of the
      lower m/z limit for ion storage. The key value of the approach is that it affords
      a relatively precise degree of control over ion temperatures as well as the time
      over which they are elevated to a higher temperature. The utility of the method
      is illustrated by the application of ion trap DDC CA in Q0 to oligonucleotide,
      protein, and multimeric protein complex analyte ions.

PMID- 24078249
TI  - Enhancement of ADP release from the RAD51 presynaptic filament by the SWI5-SFR1
      complex.
AB  - Homologous recombination catalyzed by the RAD51 recombinase eliminates
      deleterious DNA lesions from the genome. In the presence of ATP, RAD51 forms a
      nucleoprotein filament on single-stranded DNA, termed the presynaptic filament,
      to initiate homologous recombination-mediated DNA double-strand break repair. The
      SWI5-SFR1 complex stabilizes the presynaptic filament and enhances its ability to
      mediate the homologous DNA pairing reaction. Here we characterize the RAD51
      presynaptic filament stabilization function of the SWI5-SFR1 complex using
      optical tweezers. Biochemical experiments reveal that SWI5-SFR1 enhances ATP
      hydrolysis by single-stranded DNA-bound RAD51. Importantly, we show that SWI5
      SFR1 acts by facilitating the release of ADP from the presynaptic filament. Our
      results thus provide mechanistic understanding of the function of SWI5-SFR1 in
      RAD51-mediated DNA recombination. 

PMID- 24078250
TI  - Covariation between homeodomain transcription factors and the shape of their DNA
      binding sites.
AB  - Protein-DNA recognition is a critical component of gene regulatory processes but
      the underlying molecular mechanisms are not yet completely understood. Whereas
      the DNA binding preferences of transcription factors (TFs) are commonly described
      using nucleotide sequences, the 3D DNA structure is recognized by proteins and is
      crucial for achieving binding specificity. However, the ability to analyze DNA
      shape in a high-throughput manner made it only recently feasible to integrate
      structural information into studies of protein-DNA binding. Here we focused on
      the homeodomain family of TFs and analyzed the DNA shape of thousands of their
      DNA binding sites, investigating the covariation between the protein sequence and
      the sequence and shape of their DNA targets. We found distinct homeodomain
      regions that were more correlated with either the nucleotide sequence or the DNA
      shape of their preferred binding sites, demonstrating different readout
      mechanisms through which homeodomains attain DNA binding specificity. We
      identified specific homeodomain residues that likely play key roles in DNA
      recognition via shape readout. Finally, we showed that adding DNA shape
      information when characterizing binding sites improved the prediction accuracy of
      homeodomain binding specificities. Taken together, our findings indicate that DNA
      shape information can generally provide new mechanistic insights into TF binding.

PMID- 24078251
TI  - Modulation of lysine methylation in myocyte enhancer factor 2 during skeletal
      muscle cell differentiation.
AB  - Myocyte enhancer factor 2 (MEF2) is a family of transcription factors that
      regulates many processes, including muscle differentiation. Due to its many
      target genes, MEF2D requires tight regulation of transcription activity over time
      and by location. Epigenetic modifiers have been suggested to regulate MEF2
      dependent transcription via modifications to histones and MEF2. However, the
      modulation of MEF2 activity by lysine methylation, an important posttranslational
      modification that alters the activities of transcription factors, has not been
      studied. We report the reversible lysine methylation of MEF2D by G9a and LSD1 as
      a regulatory mechanism of MEF2D activity and skeletal muscle differentiation. G9a
      methylates lysine-267 of MEF2D and represses its transcriptional activity, but
      LSD1 counteracts it. This residue is highly conserved between MEF2 members in
      mammals. During myogenic differentiation of C2C12 mouse skeletal muscle cells,
      the methylation of MEF2D by G9a decreased, on which MEF2D-dependent myogenic
      genes were upregulated. We have also identified lysine-267 as a
      methylation/demethylation site and demonstrate that the lysine methylation state
      of MEF2D regulates its transcriptional activity and skeletal muscle cell
      differentiation. 

PMID- 24078253
TI  - Lung biopsy in diffuse interstitial lung disease (simple technique).
AB  - A simple, safe, easily reproducible and quick method of taking lung biopsy in
      diffuse interstitial lung disease is described.

PMID- 24078252
TI  - Genome-wide profiling reveals stimulus-specific functions of p53 during
      differentiation and DNA damage of human embryonic stem cells.
AB  - How tumor suppressor p53 selectively responds to specific signals, especially in
      normal cells, is poorly understood. We performed genome-wide profiling of p53
      chromatin interactions and target gene expression in human embryonic stem cells
      (hESCs) in response to early differentiation, induced by retinoic acid, versus
      DNA damage, caused by adriamycin. Most p53-binding sites are unique to each state
      and define stimulus-specific p53 responses in hESCs. Differentiation-activated
      p53 targets include many developmental transcription factors and, in pluripotent
      hESCs, are bound by OCT4 and NANOG at chromatin enriched in both H3K27me3 and
      H3K4me3. Activation of these genes occurs with recruitment of p53 and H3K27me3
      specific demethylases, UTX and JMJD3, to chromatin. In contrast, genes associated
      with cell migration and motility are bound by p53 specifically after DNA damage.
      Surveillance functions of p53 in cell death and cell cycle regulation are
      conserved in both DNA damage and differentiation. Comparative genomic analysis of
      p53-targets in mouse and human ESCs supports an inter-species divergence in p53
      regulatory functions during evolution. Our findings expand the registry of p53
      regulated genes to define p53-regulated opposition to pluripotency during early
      differentiation, a process highly distinct from stress-induced p53 response in
      hESCs. 

PMID- 24078254
TI  - Purification and characterization of a urethanase from Penicillium variabile.
AB  - Urethanase produced by Penicillium variabile was purified through
      ultrasonication, concentration by polyethylene glycol 20,000, and Superdex G-200
      gel filtration chromatography. The molecular weight of urethanase was determined
      to be around 96 kDa by gel filtration. The purified enzyme showed a single band
      in SDS-PAGE with the molecular weight of ~13.7 kDa, which suggests that the
      enzyme has a multimeric structure composed of the same subunits. Peptide map
      fingerprinting analysis was then carried out by MALDI/TOF-TOF MS. Within the
      known sequences in NCBI, glucosamine-6-phosphate deaminase and 6-phosphogluconate
      dehydrogenase get high score as compared with urethanase. Sequence analysis
      informs that N-terminal sequence of urethanase is GTNTADNDAA. The Minchaelis
      constant (Km) and maximum reaction rate (Vm) of urethanase are 27.2 mmol/L and
      156.25 MUmol/L min, respectively.

PMID- 24078255
TI  - Succinic acid production from corn cob hydrolysates by genetically engineered
      Corynebacterium glutamicum.
AB  - Corynebacterium glutamicum wild type lacks the ability to utilize the xylose
      fractions of lignocellulosic hydrolysates. In the present work, we constructed a
      xylose metabolic pathway in C. glutamicum by heterologous expression of the xylA
      and xylB genes coming from Escherichia coli. Dilute-acid hydrolysates of corn
      cobs containing xylose and glucose were used as a substrate for succinic acid
      production by recombinant C. glutamicum NC-2. The results indicated that the
      available activated charcoal pretreatment in dilute-acid hydrolysates of corn
      cobs could be able to overcome the inhibitory effect in succinic acid production.
      Succinic acid was shown to be efficiently produced from corn cob hydrolysates (55
      g l(-1) xylose and 4 g l(-1) glucose) under oxygen deprivation with addition of
      sodium carbonate. Succinic acid concentration reached 40.8 g l(-1) with a yield
      of 0.69 g g(-1) total sugars within 48 h. It was the first report of succinic
      acid production from corn cob hydrolysates by metabolically engineered C.
      glutamicum. This study suggested that dilute-acid hydrolysates of corn cobs may
      be an alternative substrate for the efficient production of succinic acid by C.
      glutamicum.

PMID- 24078256
TI  - Kinetic modeling of ethanol production by Scheffersomyces stipitis from xylose.
AB  - This work focuses on the kinetics of ethanol production by Scheffersomyces
      stipitis on xylose with the development of a mathematical model considering the
      effect of substrate and product concentrations on growth rate. Experiments were
      carried out in batch and continuous modes, with substrate concentration varying
      from 7.2 to 145 g L(-1). Inhibitory effects on cell growth, substrate uptake, and
      ethanol production rates were found to be considerable. Kinetic parameters were
      obtained through linear and non-linear regression methods. Experiments in
      continuous mode were performed at different dilution rates to evaluate the
      inhibitory effect of ethanol. A mixed mathematical model which combined Andrews
      and Levenspiel's models, combining substrate and product inhibition, was used. A
      quasi-Newton routine was applied to obtain a more accurate fitting of kinetic
      parameters. The parameters such as cell to product factor (YP/X) and limiting
      cell yield (YX) were shown to be dependent on substrate concentration. The
      kinetic model fitted satisfactorily the experimental data.

PMID- 24078257
TI  - NCI Cooperative Clinical Trials Groups proceed with reorganization: new system
      aims to improve efficiency and address changing research needs.

PMID- 24078258
TI  - Significant undiagnosed disease found among survivors of childhood cancer:
      researchers increasingly target metabolism in the search for new cancer
      treatments.

PMID- 24078259
TI  - Young breast cancer patients often opt for mastectomy.

PMID- 24078260
TI  - Clinical manifestations of disease in X-linked carriers of chronic granulomatous
      disease.
AB  - Chronic Granulomatous Disease (CGD) is a rare primary immunodeficiency due to a
      defect in one of the NADPH oxidase complex subunits; 70 % of cases are X-linked,
      due to a CYBB mutation, resulting in defective production of gp91PHOX. Female
      carriers of X-linked CGD have previously been considered to be unaffected. It is
      increasingly recognized that they may suffer from similar problems to CGD
      patients. This review will examine the literature about clinical manifestations
      of disease in X-linked carriers of CGD.

PMID- 24078261
TI  - Decreased NAA in gray matter is correlated with decreased availability of acetate
      in white matter in postmortem multiple sclerosis cortex.
AB  - Multiple sclerosis (MS) is an inflammatory neurodegenerative disease of the
      central nervous system (CNS) which leads to progressive neurological disability.
      Our previous studies have demonstrated mitochondrial involvement in MS cortical
      pathology and others have documented decreased levels of the neuronal
      mitochondrial metabolite N-acetyl aspartate (NAA) in the MS brain. While NAA is
      synthesized in neurons, it is broken down in oligodendrocytes into aspartate and
      acetate. The resulting acetate is incorporated into myelin lipids, linking
      neuronal mitochondrial function to oligodendrocyte-mediated elaboration of myelin
      lipids in the CNS. In the present study we show that treating human SH-SY5Y
      neuroblastoma cells with the electron transport chain inhibitor antimycin A
      decreased levels of NAA as measured by HPLC. To better understand the
      significance of the relationship between mitochondrial function and levels of NAA
      and its breakdown product acetate on MS pathology we then quantitated the levels
      of NAA and acetate in MS and control postmortem tissue blocks. Regardless of
      lesion status, we observed that levels of NAA were decreased 25 and 32 % in gray
      matter from parietal and motor cortex in MS, respectively, compared to controls.
      Acetate levels in adjacent white matter mirrored these decreases as evidenced by
      the 36 and 45 % reduction in acetate obtained from parietal and motor cortices.
      These data suggest a novel mechanism whereby mitochondrial dysfunction and
      reduced NAA levels in neurons may result in compromised myelination by
      oligodendrocytes due to decreased availability of acetate necessary for the
      synthesis of myelin lipids.

PMID- 24078262
TI  - Oxysophoridine protects against focal cerebral ischemic injury by inhibiting
      oxidative stress and apoptosis in mice.
AB  - Our previous studies have demonstrated that oxysophoridine (OSR) has protective
      effects on cerebral neurons damage in vitro induced by oxygen and glucose
      deprivation. In this study, we further investigated whether OSR could reduce
      ischemic cerebral injury in vivo and its possible mechanism. Male Institute of
      cancer research mice were intraperitoneally injected with OSR (62.5, 125 and 250
      mg/kg) for seven successive days, then subjected to brain ischemia induced by the
      model of middle cerebral artery occlusion. After reperfusion, neurological scores
      and infarct volume were estimated. Morphological examination of tissues was
      performed. Apoptotic neurons were detected by terminal deoxynucleotidyl
      transferase mediated dUTP nick end labeling staining. Oxidative stress levels
      were assessed by measurement of malondialdehyde (MDA), superoxide dismutase (SOD)
      and glutathione peroxidase (GSH-Px) levels. The expression of various apoptotic
      markers as Caspase-3, Bax and Bcl-2 were investigated by immunohistochemistry and
      Western-blot analysis. OSR pretreatment groups significantly reduced infract
      volume and neurological deficit scores. OSR decreased the percentage of apoptotic
      neurons, relieved neuronal morphological damage. Moreover, OSR markedly decreased
      MDA content, and increased SOD, GSH-Px activities. Administration of OSR (250
      mg/kg) significantly suppressed overexpression of Caspase-3 and Bax, and
      increased Bcl-2 expression. These findings indicate that OSR has a protective
      effect on focal cerebral ischemic injury through antioxidant and anti-apoptotic
      mechanisms.

PMID- 24078263
TI  - The CacyBP/SIP protein is sumoylated in neuroblastoma NB2a cells.
AB  - The Calcyclin binding protein and Siah-1 interacting protein (CacyBP/SIP) protein
      is highly expressed in mammalian brain as well as in neuroblastoma NB2a cells and
      pheochromocytoma PC12 cells. This protein interacts with several targets such as
      cytoskeletal proteins or ERK1/2 kinase and seems to be involved in many cellular
      processes. In this work we examined a post-translational modification of
      CacyBP/SIP which might have an effect on its function. Since theoretical analysis
      of the amino acid sequence of CacyBP/SIP indicated several lysine residues which
      could potentially be sumoylated we checked experimentally whether this protein
      might be modified by SUMO attachment. We have shown that indeed CacyBP/SIP bound
      the E2 SUMO ligase, Ubc9, in neuroblastoma NB2a cell extract and was sumoylated
      in these cells. By fractionation of NB2a cell extract we have found that,
      contrary to the majority of SUMO-modified proteins, sumoylated CacyBP/SIP is
      present in the cytoplasmic and not in the nuclear fraction. We have also
      established that lysine 16 is the residue which undergoes sumoylation in the
      CacyBP/SIP protein.

PMID- 24078264
TI  - Modulation of ionotropic GABA receptors by 6-methoxyflavanone and 6
      methoxyflavone.
AB  - We evaluated the effects of 6-methoxyflavanone and 6-methoxyflavone on wild-type
      alpha1/alpha2beta2gamma2L GABAA and rho1 GABAC receptors and on mutant rho1I307S,
      rho1W328 M, rho1I307S/W328 M GABAC receptors expressed in Xenopus oocytes using
      two-electrode voltage clamp and radioligand binding. 6-Methoxyflavanone and 6
      methoxyflavone act as a flumazenil-insensitive positive allosteric modulator of
      GABA responses at human recombinant alpha1beta2gamma2L and alpha2beta2gamma2L
      GABAA receptors. However, unlike 6-methoxyflavone, 6-methoxyflavanone was
      relatively inactive at alpha1beta2 GABAA receptors. 6-Methoxyflavanone inhibited
      [(3)H]-flunitrazepam binding to rat brain membranes. Both flavonoids were found
      to be inactive as modulators at rho1, rho1I307S and rho1W328 M GABA receptors but
      acted as positive allosteric modulators of GABA at the benzodiazepine sensitive
      rho1I307S/W328 M GABA receptors. This double mutant retains rho1 properties of
      being insensitive to bicuculline and antagonised by TPMPA and THIP. Additionally,
      6-methoxyflavanone was also a partial agonist at rho1W328 M GABA receptors. The
      relative inactivity of 6-methoxyflavanone at alpha1beta2 GABAA receptors and it's
      partial agonist action at rho1W328 M GABA receptors suggest that it exhibits a
      unique profile not matched by other flavonoids. 

PMID- 24078265
TI  - Dynactin Deficiency in the CNS of Humans with Sporadic ALS and Mice with
      Genetically Determined Motor Neuron Degeneration.
AB  - Dynactin is a complex motor protein involved in the retrograde axonal transport
      disturbances of which may lead to amyotrophic lateral sclerosis (ALS). Mice with
      hSOD1G93A mutation develop ALS-like symptoms and are used as a model for the
      disease studies. Similar symptoms demonstrate Cra1 mice, with Dync1h1 mutation.
      Dynactin heavy (DCTN1) and light (DCTN3) subunits were studied in the CNS of
      humans with sporadic ALS (SALS), mice with hSOD1G93A (SOD1/+), Dync1h1 (Cra1/+),
      and double (Cra1/SOD1) mutation at presymptomatic and symptomatic stages. In SALS
      subjects, in contrast to control cases, expression of DCTN1-mRNA but not DCTN3
      mRNA in the motor cortex was higher than in the sensory cortex. However, the mean
      levels of DCTN1-mRNA and protein were lower in both SALS cortexes and in the
      spinal cord than in control structures. DCTN3 was unchanged in brain cortexes but
      decreased in the spinal cord on both mRNA and protein levels. In all SALS tissues
      immunohistochemical analyses revealed degeneration and loss of neuronal cells,
      and poor expression of dynactin subunits. In SOD1/+ mice both subunits expression
      was significantly lower in the frontal cortex, spinal cord and hippocampus than
      in wild-type controls, especially at presymptomatic stage. Fewer changes occurred
      in Cra1/SOD1 and Cra1/+ mice.It can be concluded that in sporadic and SOD1
      related ALS the impairment of axonal retrograde transport may be due to dynactin
      subunits deficiency and subsequent disturbances of the whole dynein/dynactin
      complex structure and function. The Dync1h1 mutation itself has slight negative
      effect on dynactin expression and it alleviates the changes caused by SOD1G93A
      mutation.

PMID- 24078266
TI  - Intravenous Administration of Human Umbilical Cord Mesenchymal Stem Cells
      Improves Cognitive Impairments and Reduces Amyloid-Beta Deposition in an
      AbetaPP/PS1 Transgenic Mouse Model.
AB  - Alzheimer's disease (AD) is characterized by Amyloid-beta (Abeta) deposition in
      senile plaques in specific areas of the brain and by intraneuronal p-tau
      accumulation in neurofibrillary tangles. Cumulative evidence supports that
      oxidative stress is an important factor in the pathogenesis of AD and contributes
      to Abeta generation. However, there is no effective treatment for AD. Human
      umbilical cord mesenchymal stem cells (HUMSCs) have potential therapeutic value
      for the treatment of neurological disease. However, the therapeutic impact of
      systemic administration of HUMSCs and their mechanism of action in AD have not
      yet been determined. Here, we found that intravenous infusion of HUMSCs
      significantly improved spatial learning and alleviated memory decline in an
      AbetaPP/PS1 mouse model of AD. HUMSC treatment also increased glutathione (GSH)
      activity and ratio of GSH to oxidative glutathione as well as superoxide
      dismutase activity, while decreasing malondialdehyde activity and protein
      carbonyl level, which suggests that HUMSC infusion alleviated oxidative stress in
      AbetaPP/PS1 mice. In addition, HUMSC infusion reduced beta-secretase 1 and
      CTFbeta, thus reducing Abeta deposition in mice. HUMSCs may have beneficial
      effects in the prevention and treatment of AD.

PMID- 24078268
TI  - Implicit and explicit clinical ethics support in The Netherlands: a mixed methods
      overview study.
AB  - Internationally, the prevalence of clinical ethics support (CES) in health care
      has increased over the years. Previous research on CES focused primarily on
      ethics committees and ethics consultation, mostly within the context of hospital
      care. The purpose of this article is to investigate the prevalence of different
      kinds of CES in various Dutch health care domains, including hospital care,
      mental health care, elderly care and care for people with an intellectual
      disability. A mixed methods design was used including two survey questionnaires,
      sent to all health care institutions, two focus groups and 17 interviews with
      managing directors or ethics support staff. The findings demonstrate that the
      presence of ethics committees is relatively high, especially in hospitals. Moral
      case deliberation (MCD) is available in about half of all Dutch health care
      institutions, and in two-thirds of the mental health care institutions. Ethics
      consultants are not very prominent. A distinction is made between explicit CES
      forms, in which the ethical dimension of care is structurally and professionally
      addressed and implicit CES forms, in which ethical issues are handled indirectly
      and in an organic way. Explicit CES forms often go together with implicit forms
      of CES. MCD might function as a bridge between the two. We conclude that explicit
      and implicit CES are both relevant for clinical ethics in health care. We
      recommend research regarding how to combine them in an appropriate way.

PMID- 24078269
TI  - Geometric design of microfluidic chambers: platelet adhesion versus accumulation.
AB  - Arterial, platelet-rich thrombosis depends on shear rates and integrin binding to
      either a collagen surface or to the growing thrombus, which are mechanistically
      different. In general, small microfluidic test sections may favor platelet
      surface adhesion without testing for the primary mode of intra-arterial
      thrombosis, i.e. platelet-platelet bonding and accumulation. In the present
      report, the ratio of platelet-platelet to platelet-surface interactions, R, and
      the percentage of platelet-platelet interactions, P, are estimated using an
      analytical approach for circular and rectangular test sections. Results show that
      the test section geometry strongly affects both R and P, with test section height
      in low-aspect ratio channels or diameter greater than 90 MUm dominated by
      platelet-platelet interactions (R >10). Increasing rectangular test section
      aspect ratio decreases the required height. R increases linearly while P
      approaches 100 % asymptotically with increasing channel dimension. Analysis of
      platelet shape shows that the assumption of spherical platelets has a small
      effect on R compared to discoid platelets adhering flat against test section
      wall. However, an increase in average platelet volume resulted in a large
      decrease in R. Nonetheless, Monte Carlo simulations of a typical distribution of
      human platelet sizes show intrasubject variation in platelet size has only a 10 %
      net effect on R. Finally, experiments of thrombus formation show that platelet
      surface lag times and platelet-platelet accumulation are similar for rectangular
      microfluidic test sections and round test sections when R >10. The findings show
      that the size of a microfluidic test section should be carefully considered in
      studies of cell-cell accumulation versus cell-surface adhesion.

PMID- 24078270
TI  - Parametric control of collision rates and capture rates in geometrically enhanced
      differential immunocapture (GEDI) microfluidic devices for rare cell capture.
AB  - The enrichment and isolation of rare cells from complex samples, such as
      circulating tumor cells (CTCs) from whole blood, is an important engineering
      problem with widespread clinical applications. One approach uses a microfluidic
      obstacle array with an antibody surface functionalization to both guide cells
      into contact with the capture surface and to facilitate adhesion; geometrically
      enhanced differential immunocapture is a design strategy in which the array is
      designed to promote target cell-obstacle contact and minimize other interactions
      (Gleghorn et al. 2010; Kirby et al. 2012). We present a simulation that uses
      capture experiments in a simple Hele-Shaw geometry (Santana et al. 2012) to
      inform a target-cell-specific capture model that can predict capture probability
      in immunocapture microdevices of any arbitrary complex geometry. We show that
      capture performance is strongly dependent on the array geometry, and that it is
      possible to select an obstacle array geometry that maximizes capture efficiency
      (by creating combinations of frequent target cell-obstacle collisions and shear
      stress low enough to support capture), while simultaneously enhancing purity by
      minimizing nonspecific adhesion of both smaller contaminant cells (with
      infrequent cell-obstacle collisions) and larger contaminant cells (by focusing
      those collisions into regions of high shear stress).

PMID- 24078271
TI  - The aggressive peripheral T-cell lymphomas: 2013.
AB  - BACKGROUND: T-cell lymphomas make up approximately 10-15% of lymphoid
      malignancies. The frequency of these lymphomas varies geographically, with the
      highest incidence in parts of Asia. DIAGNOSIS: The diagnosis of aggressive
      peripheral T-cell lymphoma (PTCL) is usually made using the WHO classification.
      The ability of hematopathologists to reproducibly diagnosis aggressive PTCL is
      lower than for aggressive B-cell lymphomas, with a range of 72-97% for the
      aggressive PTCLs. RISK STRATIFICATION: Patients with aggressive PTCL are staged
      using the Ann Arbor Classification. Although somewhat controversial, PET scans
      appear to be useful as they are in aggressive B-cell lymphomas. The most commonly
      used prognostic index is the International Prognostic Index. The specific subtype
      of aggressive PTCL is an important risk factor, with the best survival seen in
      anaplastic large cell lymphoma-particularly young patients with the anaplastic
      lymphoma kinase positive subtype. RISK ADAPTED THERAPY: Anaplastic large cell
      lymphoma is the only subgroup to have a good response to a CHOP-like regimen.
      Angioimmunoblastic T-cell lymphoma has a prolonged disease-free survival in only
      ~20% of patients, but younger patients who have an autotransplant in remission
      seem to do better. PTCL-NOS (not otherwise specified) is not one disease.
      Anthracycline containing regimens have disappointing results and a new approach
      is needed. NK/T-cell lymphoma localized to the nose and nasal sinuses seems to be
      best treated with radiotherapy containing regimens. Enteropathy associated PTCL
      and hepatosplenic PTCL are rare disorders with a generally poor response to
      therapy, although selected patients with enteropathy associated PTCL seem to
      benefit from intensive therapy.

PMID- 24078272
TI  - Rapid screening of different chelating agents in the lead extraction from cathode
      ray tube (CRT) funnel glass.
AB  - The cathode ray tube (CRT) glass is one of the most important problem that
      afflicts the electronic waste disposal whose solution lies in the identification
      of efficient and ecofriendly processes to detoxify and reutilize lead-contained
      funnel glass. This study is focused on a rapid screening of different chemical
      and mechanochemical processes to reduce lead content in waste CRT glass
      downgrading the risk correlated to it. In particular, as a possibility to clean
      waste CRT glass, treatments of lead-containing glass with different chelating
      agents (EDTA, NTA, ATMP, EDTMP and HEDP) were performed to evaluate their
      extractive capabilities. Furthermore, the influence of the grinding, the
      chelating agent functional groups (polyamino-carboxylic acid, carboxylic acid,
      and polyamino phosphonic acid), and the time and the temperature on lead content
      reduction were analyzed. ESEM and EDS analysis were performed on all the samples
      to evaluate the lead amount before and after the treatments.

PMID- 24078273
TI  - Urinary concentrations of trichlorophenols in the Korean adult population:
      results of the National Human Biomonitoring Survey 2009.
AB  - Trichlorophenols such as 2,4,5-trichlorophenol (2, 4,5-TCP) and 2,4,6
      trichlorophenol (2,4,6-TCP) are organochlorine compounds to which the general
      public can be exposed via contaminated food, water, and air. This study assessed
      exposure to 2,4,5-TCP and 2,4,6-TCP in Koreans age 18-69 years based on the
      Korean National Human Biomonitoring Survey conducted in 2009. Using data from
      1,865 representative Koreans, we found that the geometric mean urinary
      concentrations of 2,4,5-TCP and 2,4,6-TCP were 83.4 pg/mL [95 % confidence
      interval (CI)=78.6-88.6] and 0.39 ng/mL (95 % CI=0.35-0.42), respectively. The
      creatinine-adjusted geometric mean 2,4,5-TCP and 2,4, 6-TCP levels were 78.8 ng/g
      creatinine (95 % CI=73.8-84.1) and 0.36 MUg/g creatinine (95 % CI=0.33-0.40),
      respectively. Of the Korean adult population, about 67.5 and 87.5 % had
      respective urine 2,4,5-TCP and 2,4,6-TCP concentrations >0.05 ng/mL (the limit of
      detection, LOD). Urine 2,4,5-TCP concentrations were significantly associated
      with age and place of residence, whereas urine 2,4,6-TCP concentrations were
      higher in rural residents. These findings suggest that most Koreans had
      detectable levels of 2,4,5-TCP and 2,4,6-TCP in their urine and that the body
      burden of 2,4,5-TCP and 2,4,6-TCP varied according to demographic and geographic
      factors.

PMID- 24078274
TI  - Pyrolysis temperature influences ameliorating effects of biochars on acidic soil.
AB  - The biochars were prepared from straws of canola, corn, soybean, and peanut at
      different temperatures of 300, 500, and 700  degrees C by means of oxygen-limited
      pyrolysis.Amelioration effects of these biochars on an acidic Ultisol were
      investigated with incubation experiments, and application rate of biochars was 10
      g/kg. The incorporation of these biochars induced the increase in soil pH, soil
      exchangeable base cations, base saturation, and cation exchange capacity and the
      decrease in soil exchangeable acidity and exchangeable Al. The ameliorating
      effects of biochars on acidic soil increased with increase in their pyrolysis
      temperature. The contribution of oxygen-containing functional groups on the
      biochars to their ameliorating effects on the acidic soil decreased with the rise
      in pyrolysis temperature, while the contribution from carbonates in the biochars
      changed oppositely. The incorporation of the biochars led to the decrease in soil
      reactive Al extracted by 0.5mol/L CuCl2, and the content of reactive Al was
      decreased with the increase in pyrolysis temperature of incorporated biochars.
      The biochars generated at 300  degrees C increased soil organically complexed Al
      due to ample quantity of oxygen-containing functional groups such as carboxylic
      and phenolic groups on the biochars, while the biochars generated at 500 and 700 
      degrees C accelerated the transformation of soil exchangeable Al to hydroxyl-Al
      polymers due to hydrolysis of Al at higher pH. Therefore, the crop straw-derived
      biochars can be used as amendments for acidic soils and the biochars generated at
      relatively high temperature have great ameliorating effects on the soils.

PMID- 24078275
TI  - Effect of long-term dietary lead exposure on some maturation and reproductive
      parameters of a female Prussian carp (Carassius gibelio B.).
AB  - Lead is reported to be an endocrine disruptor. In the current study, we exposed
      female Prussian carp to artificial feed, supplemented with five doses of dietary
      Pb (0, 1 (control), 8, 13, 24, and 49 mg/kg) over either a 24-month period or a
      12-month period, followed by further 12 months where the fish were fed the
      control diet. Periodically, oocyte maturation, gonadosomatic index (GSI), ability
      to secret luteinizing hormone (LH) as well as gonad Pb concentrations were
      measured. It was found that the reproductive system of the female Prussian carp
      is not indifferent to chronic exposure to lead. The negative effect was
      manifested by a decrease in the GSI after 12 months despite the fact that a
      higher proportion of oocytes at more advanced maturity stages were concurrently
      observed. After 12 months of exposure, the effect on LH secretion varied
      according to the dose. In the group exposed to the lowest dose (8 mg/kg), LH
      decreased spontaneously, and in the groups exposed to the highest two doses (24
      and 48 mg/kg), a significantly higher LHRH-A-stimulated LH secretion was
      observed. After 24 months of lead exposure, the effects on oocyte maturation and
      size and on GSI values were not pronounced. Analysis of the effect of lead
      exposure on LH secretion showed that the relationships were similar to those
      observed after 12 months but nonsignificant. During chronic a 24-month period
      exposure to Pb, Prussian carp female appears to acclimate to Pb doses used in the
      experiment. After 12 months of exposure and 12 months of depuration, the levels
      of spontaneous and stimulated LH secretion observed in all the groups were
      similar to the control, which is evidence that depuration eliminates the
      previously observed effects of exposure to lead. Lead is easily accumulated in
      the ovary, reaching a fivefold higher level (0.8 mg/kg tissue) compared to the
      control(0.15 mg/kg tissue), but after discontinuation of exposure, this organ is
      quickly depurated. The results indicate that environmental Pb can be a potent
      endocrine disruptor affecting ovarian steroidogenesis, gametogenesis, and
      ovulation, which may lead to adverse impacts on fish reproduction and population
      density and that female Prussian carp become resistant to the negative effects of
      lead with advancing age, and their organs cope by reaching a state of
      homeostasis.

PMID- 24078278
TI  - Relationship between absolute neutrophil count profiles and pharmacokinetics of
      DA-3031, a pegylated granulocyte colony-stimulating factor (pegylated-G-CSF): a
      dose block-randomized, double-blind, dose-escalation study in healthy subjects.
AB  - BACKGROUND: DA-3031 is a newly developed pegylated filgrastim, a recombinant
      human granulocyte colony-stimulating factor, that is expected to have an extended
      duration of action compared with non-modified filgrastim. OBJECTIVE: This study
      evaluated the tolerability, pharmacokinetics, and pharmacodynamics of DA-3031 in
      humans, and compared them with filgrastim. METHODS: The study was conducted in 48
      healthy male Korean subjects. Forty subjects received subcutaneous single doses
      of 1.8, 3.6, 6, or 18 mg of DA-3031 or placebo in a dose block-randomized, double
      blind, dose-escalation design. The remaining eight subjects were given
      subcutaneous doses of 100 MUg/m2 of filgrastim daily for 5 days. Serial blood
      samples were collected for pharmacokinetic and pharmacodynamic analyses up to 312
      h after the administration of DA-3031 and up to 264 h following the first
      administration of filgrastim. RESULTS: DA-3031 reached its peak plasma
      concentration at 6.0-48.0 h and was eliminated mono-exponentially. The
      pharmacokinetic parameters of DA-3031 increased with dose in a non-linear
      fashion. Absolute neutrophil count (ANC) levels increased with the dose of DA
      3031, although the extent of the increase in ANC decreased at higher dose levels.
      DA-3031 resulted in similar ANC changes in the 3.6 to 6 mg dose range as 100
      MUg/m2 of filgrastim. The most frequent adverse event was back pain, which was
      observed after both DA-3031 and filgrastim administration. CONCLUSIONS: DA-3031
      showed non-linear pharmacodynamic and pharmacokinetic profiles and an extended
      duration of action compared with non-modified filgrastim, without unexpected
      toxicities in healthy subjects.

PMID- 24078279
TI  - Neutrophil-to-lymphocyte ratio in chronic obstructive pulmonary disease: a
      retrospective study.
AB  - Chronic obstructive pulmonary disease (COPD) is a common chronic inflammatory
      disease of the lung with a high mortality and morbidity rate. Some of the
      inflammatory markers such as C-reactive protein (CRP), leukocyte count are
      associated with COPD. In this study, we aimed to evaluate the role of neutrophil
      to-lymphocyte ratio (NLR) in COPD patients comparing with the other well-known
      inflammatory markers. We retrospectively enrolled the laboratory results of 269
      COPD patients of which 178 patients at stable period and 91 patients during acute
      exacerbation and 50 sex- and age- matched healthy controls. We found that NLR
      values of the stable COPD patients were significantly higher than those of the
      controls (P < 0.001). During acute exacerbation of the disease there was a
      further increase compared to stable period (P < 0.001). NLR values were also
      positively correlated with serum CRP levels and red cell distribution width (RDW)
      and negatively correlated with mean platelet volume (MPV) in both COPD groups. In
      conclusion, NLR could be considered as a new inflammatory marker for assessment
      of inflammation in COPD patients with its quick, cheap, easily measurable
      property with routine complete blood count analysis. 

PMID- 24078280
TI  - Training the novice to become cardiac surgeon: does the "early learning curve"
      training compromise surgical outcomes?
AB  - OBJECTIVE: It is unclear whether novice trainees can be taught safely to perform
      adult cardiac surgery without any impact on early or late outcomes. METHODS: All
      patients (n = 1305) data were obtained from an externally validated, mandatory
      institutional database (2003-2010). 'Novice' is defined as a trainee who required
      substantial assistance or supervision to perform part or whole of the specified
      procedure (Intercollegiate Surgical Curriculum Programme UK, Competency Level
      <=2). Outcome measures were in-hospital mortality, composite score of in-hospital
      mortality-morbidities, mid-term survival and revascularisation rate after CABG.
      Follow-up up to 7 years (median 3.2 years) was determined. RESULTS: Some 39 % (n
      = 510) of the cases involved novice (28 %-part, 11 %-whole procedure), 12 % (n =
      157) competent trainees and 49 % (n = 638) consultant. Median EuroSCORE was
      higher in consultant group (p < 0.001). Without risk adjustment, composite
      outcome score and mid-term mortality were higher in consultant group (p = 0.03).
      With adjustment using EuroSCORE and propensity scores, EuroSCORE was
      significantly predictive of in-hospital mortality [odd ratio (OR) 1.38, 95 %CI
      1.20-1.57, p < 0.001], composite outcome (OR 1.26, 95 %CI 1.15-1.37, p < 0.001)
      and mid-term mortality (HR 1.24, 95 %CI 1.18-1.31, p < 0.001) but not the
      operator categories. Further analysis of subcohort undergoing first-time,
      isolated CABG (n = 1070) showed that EuroSCORE remained predictive of adjusted in
      hospital mortality (OR 1.39, 95 %CI 1.13-1.71, p = 0.002), composite outcome (OR
      1.33, 95 %CI 1.19-1.49, p < 0.001) and mid-term mortality (HR 1.22, 95 %CI 1.10
      1.35, p < 0.001). The operator categories were not associated with adjusted
      outcome measures including revascularisation rate after CABG. CONCLUSION:
      Supervised training in adult cardiac surgery can be achieved safely at the early
      learning curve phase without compromising both early and mid-term clinical
      outcomes.

PMID- 24078281
TI  - Introduction of cardiac surgery residency program at an earlier stage in surgical
      training.
AB  - OBJECTIVE: Reform of the Japanese postgraduate residency program has dramatically
      influenced the recruitment system. Because shortage of young cardiac surgeons is
      anticipated, an effective program for residents who want to become cardiac
      surgeons must be established at an earlier stage in surgical training. METHODS: A
      3-year cardiac surgery residency curriculum was developed for senior residents.
      The surgical training program includes harvesting of the saphenous vein, radial
      artery and internal thoracic artery, and repair of abdominal aortic aneurysm and
      specifies the target number of surgical procedures for each training. Academic
      training is provided in addition to clinical skills training. Nine residents
      completed the 3-year program between 2004 and 2012. The number of surgical
      procedures performed, presentations made at scientific meetings, and scientific
      papers published were investigated and analyzed. RESULTS: Each resident
      participated in 438 operations during 3-year program, 25.9 +/- 8.3 (5.9 %) as
      main operator and 182.2 +/- 15.8 (42 %) as first assistant. The average number of
      procedures per resident over the 3 years was 43.0 +/- 6.7 for saphenous vein
      harvest, 14.4 +/- 3.9 for radial artery harvest, 27.9 +/- 13.0 for internal
      thoracic artery harvest, 7.1 +/- 4.6 for abdominal aortic aneurysm. In addition,
      over the 3 years, the mean number of presentations at scientific meetings was
      13.2 +/- 3.2 and the mean number of publication of scientific papers was 1.9 +/-
      1.4. CONCLUSION: The new cardiac surgery training curriculum for residents worked
      fairly well. A system for assessment of the program by an authoritative body
      should be established in the future.

PMID- 24078282
TI  - Ovarian and tubal torsion: imaging findings on US,  CT, and MRI.
AB  - Accurate diagnosis of adnexal torsion is often challenging, as clinical
      presentation is nonspecific and the differential for pelvic pain is broad.
      However, prompt diagnosis and treatment is critical to good clinical outcomes and
      preservation of the ovary and/or fallopian tube. Ultrasound (US) imaging is most
      frequently used to assess torsion. However, as computed tomography (CT)
      utilization in the emergency setting has increased, there are times when CT is
      the initial imaging test. Additionally, the nonspecific clinical presentation may
      initially be interpreted as gastrointestinal in etiology, where CT is the
      preferred exam. For these reasons, it is imperative to know the findings of
      adnexal torsion on CT as well as US. Magnetic resonance imaging (MRI) is helpful
      in cases where the diagnosis remains unclear and is particularly helpful in the
      young or pregnant patient with equivocal sonographic findings, as it provides
      excellent soft tissue contrast without ionizing radiation. This article will
      illustrate the findings of surgically confirmed ovarian and fallopian tube
      torsion on US, CT, and MRI, including those in the pregnant patient. Ovarian
      enlargement, adnexal mass, twisting of the vascular pedicle, edematous and
      heterogeneous appearance of the ovary, peripheral ovarian follicles, free fluid,
      uterine deviation towards the side of torsion, adnexal fat stranding, tubal
      dilatation, and decreased adnexal enhancement will be reviewed. Familiarity with
      the range of imaging findings across multiple modalities is key to improving the
      likelihood of timely diagnosis and therefore improved clinical outcomes.

PMID- 24078283
TI  - Advanced glycation end products and diabetic nephropathy: a comparative study
      using diabetic and normal rats with methylglyoxal-induced glycation.
AB  - Hyperglycemia-related advanced glycation end product (AGE) formation is a key
      mechanism in diabetic nephropathy. Since methylglyoxal (MG) is a potent AGE
      precursor, we aimed to assess the role of MG-related AGE formation in the
      progression of renal damages. A comparative study between Wistar (W, normal) and
      Goto-Kakizaki (GK, nonobese type 2 diabetic) rats was performed at 6 and 14
      months old and after 14 weeks of MG administration to 6-month-old rats. Diabetic
      rats showed progressive structural, biochemical, and functional alterations,
      including AGE, albuminuria, and tissue hypoxia, which were partially mimicked by
      MG administration to young GK rats. Aged Wistar rats had an impairment of some
      parameters, whereas MG administration caused a phenotype similar to young GK
      rats, including oxidative stress, impaired apoptotic and angiogenic markers, and
      structural lesions. MG accumulation specifically impaired several of the renal
      disease markers progressively observed in diabetic rats, and thus, it contributes
      to the progression of diabetic nephropathy.

PMID- 24078284
TI  - Mas-related G protein-coupled receptor D is coupled to endogenous calcium
      activated chloride channel in Xenopus oocytes.
AB  - Mas-related G protein-coupled receptor D (MrgD) is expressed almost exclusively
      in nociceptive primary sensory neurons and the neurons located in stratum
      granulosum of skin. More and more evidence suggest that MrgD plays an important
      role in pain sensation and/or transduction. Recent studies have demonstrated that
      the receptor is also involved in itch sensation in both mouse and human. In the
      present study, we identified a robust inward current in MrgD-expressing Xenopus
      oocytes by using beta-alanine, a putative ligand of MrgD. The currents were
      sensitive to inhibitor of Ca(2+)-activated chloride channels (CaCCs) and
      intracellular Ca(2+) chelator, suggesting they were produced by endogenous CaCCs.
      Furthermore, it was demonstrated that upon the application of phospholipase C
      (PLC) inhibitor, or antisense oligonucleotides of inositol trisphosphate receptor
      (IP3R), the beta-alanine-induced currents were dramatically depressed. However,
      protein kinase C inhibitor did not display any visible effect on CaCC currents.
      In summary, our data suggest that the activation of MrgD promotes the open of
      endogenous CaCCs via G(q)-PLC-IP3-Ca(2+) pathway. The current findings reveal the
      functional coupling between MrgD and CaCCs in Xenopus oocytes and also provide a
      facile model to assay the activity of MrgD.

PMID- 24078285
TI  - The plume also rises: trajectories of pheromone plumes issuing from point sources
      in an orchard canopy at night.
AB  - The trajectories of pheromone plumes in canopied habitats, such as orchards, have
      been little studied. We documented the capture of male navel orangeworm moths,
      Amyelois transitella, in female-baited traps positioned at 5 levels, from ground
      level to the canopy top, at approximately 6 m above ground, in almond orchards.
      Males were captured in similar proportions at all levels, suggesting that they do
      not favor a particular height during ranging flight. A 3-D sonic anemometer was
      used to establish patterns of wind flow and temperature at 6 heights from 2.08 to
      6.65 m in an almond orchard with a 5 m high canopy, every 3 h over 72 h. The
      horizontal velocity of wind flow was highest above the canopy, where its
      directionality also was the most consistent. During the time of A. transitella
      mating (0300-0600), there was a net vertical displacement upward. Vertical
      buoyancy combined with only minor reductions in the distance that plumes will
      travel in the lower compared to the upper canopy suggest that the optimal height
      for release of pheromone from high-release rate sources, such as aerosol
      dispensers ("puffers"), that are deployed at low densities (e.g., 3 per ha.)
      would be at mid or low in the canopy, thereby facilitating dispersion of
      disruptant throughout the canopy. Optimal placement of aerosol dispensers will
      vary with the behavioral ecology of the target pest; however, our results suggest
      that current protocols, which generally propose dispenser placement in the upper
      third of the canopy, should be reevaluated.

PMID- 24078286
TI  - Prediction of H3 receptor occupancy diurnal fluctuations using population
      modeling and simulation with focus on guiding dose selection in a Phase IIa
      study.
AB  - PURPOSE: 4-[(1S,2S)-2-(4-cyclobutylpiperazine-1-carbonyl)cyclopropyl]benzamide
      ("AZ1") is a histamine 3 (H3) autoreceptor in vivo antagonist. Sleep disturbance
      is a well-known class-effect for H3 antagonists and associated with high H3
      receptor occupancy (RO) at night. The objective of the present work was to
      investigate if it was possible to obtain large diurnal fluctuations in RO for AZ1
      and to suggest suitable doses for a Phase IIa study. METHODS: Four Phase I
      studies were pooled and used to build a population pharmacokinetic model in
      NONMEM. Based on simulations of the PK model and the reported Ki-value for H3 RO
      from a human PET-study, RO vs. time profiles were simulated. RESULTS: The model
      well described the AZ1 pharmacokinetics. Simulations predicting plasma
      concentration and RO vs. time profiles for several doses were explored and doses
      with a wide range of fluctuation in RO over the dosing interval could be
      identified. CONCLUSIONS: By using population modeling and simulations of PK data
      and the Ki-value from a human PET study, predictions of RO vs. time for unstudied
      doses of AZ1 was made. Using this methodology it was possible to suggest doses
      with expected large diurnal fluctuations in RO.

PMID- 24078288
TI  - Complications of "very high" leukocytosis in pediatric acute leukemia patients
      managed without rasburicase and leukopheresis.
AB  - The authors evaluated complications in pediatric acute leukemia with "very high"
      leukocytosis (VHL) prior to rasburicase availability and without leukopheresis.
      From Jun 2003 through Dec 2009, 45 out of 457 (10 %) pediatric acute leukemia
      patients had VHL. Median WBC for acute lymphoblastic leukemia (ALL) and acute
      myeloid leukemia (AML) patients was 296,500/mm3 (200,000-615,220) and 206,300/mm3
      (106,100-541,900) respectively. Laboratory and clinical tumor-lysis-syndrome was
      seen in 37.7 % and 13.3 % patients respectively; none required dialysis; 6.6 %
      died due to CNS/pulmonary bleed. Thrombocytopenia <31,000/mm3 was associated with
      hypocalcemia (p = 0.04) and mortality (p = 0.04), and hypoalbuminemia with kidney
      dysfunction (p = 0.04). In resource-limited setting, VHL patients with
      thrombocytopenia may warrant rasburicase with or without leukopheresis, and
      aggressive platelet support.

PMID- 24078287
TI  - Regulation of cytochrome b5 expression by miR-223 in human liver: effects on
      cytochrome P450 activities.
AB  - PURPOSE: Cytochrome b5 (b5) is a hemoprotein that transfers electrons to several
      enzymes to fulfill functions in fatty acid desaturation, methemoglobin reduction,
      steroidogenesis, and drug metabolism. Despite the importance of b5, the
      regulation of b5 expression in human liver remains largely unknown. We
      investigated whether microRNA (miRNA) might be involved in the regulation of
      human b5. METHODS: Twenty-four human liver specimens were used for correlation
      analysis. In silico analysis and luciferase assay were performed to determine
      whether the predicted miRNAs functionally target to b5. The miR-223 was
      overexpressed into HepG2 cells infected with adenovirus expressing human
      cytochrome P450. RESULTS: In human livers, the b5 protein levels were not
      positively correlated with the b5 mRNA levels, and miR-223 levels were inversely
      correlated with the b5 mRNA levels or the translational efficiencies. The
      luciferase assay showed that miR-223 functionally binds to the element in the 3'
      untranslated region of b5 mRNA. The overexpression of miR-223 significantly
      reduced the endogenous b5 protein level and the mRNA stability in HepG2 cells.
      Moreover, the overexpression of miR-223 significantly reduced CYP3A4-catalyzed
      testosterone 6beta-hydroxylation activity and CYP2E1-catalyzed chlorzoxazone 6
      hydroxylase activity but not CYP1A2-catalyzed 7-ethoxyresorufin O-deethylase
      activity. CONCLUSIONS: miR-223 down-regulates b5 expression in the human liver,
      modulating P450 activities.

PMID- 24078289
TI  - Surface electromyography in premature infants: a series of case reports and their
      methodological aspects.
AB  - OBJECTIVES: To analyze the development of a method for using Surface
      Electromyography (sEMG) to evaluate the suckling of premature infants and
      describe five case reports. METHODS: The five premature infants who took part in
      the study were submitted to sEMG evaluation of the masseter and buccinator
      muscles during different feeding methods. RESULTS: Higher masseter muscle
      activity was observed in the infants that breastfed or used a cup; masseter
      muscle activity was reduced and buccinator muscle activity was increased in
      infants who were fed artificially using only a bottle. CONCLUSIONS: Masseter
      action was reduced in bottle-fed infants, and there were similarities in masseter
      activity during breastfeeding and cup-feeding.

PMID- 24078290
TI  - Editorial: allergy and immunology.

PMID- 24078291
TI  - A single centre experience of active surveillance as management strategy for low
      risk prostate cancer in Ireland.
AB  - INTRODUCTION: Active surveillance (AS) is a management strategy for addressing
      the widely acknowledged problem of over diagnosis and over treatment of
      clinically indolent prostate cancer. METHODS: A total of 80 patients were
      enrolled on the AS program in our institution between January 2008 and June 2012.
      All data were collected prospectively in a secure database. RESULTS: The mean age
      of patients enrolled was 62.7 years (range 50-72). Median PSA at enrolment was
      5.6 ng/mL (range 1.2-13.4). The mean follow-up was 32 months (range 2-54). In
      total, 85 % of patients had a repeat biopsy after 1-year with 30 % having another
      biopsy after 3 years. Overall, 45 % of patients remain on AS. In the remainder;
      42.5 % of patients have been removed from AS for definitive treatment, while 8.75
      % of patients are now on watchful waiting, 2.5 % of patients self discharged from
      the program and one patient died of cardiovascular disease. The prostate cancer
      specific survival rate is 100 %. Reasons for removal from AS and referral for
      treatment were; 67.6 % of patients had upgrade of disease on repeat biopsy, 17.6
      % of patients had PSA progression, 11.8 % patients had progression of disease on
      MRI, and one patient developed a palpable nodule. Regarding definitive treatment;
      52.9 % of patients have been for referred for external beam radiotherapy, 14.7 %
      have been referred for brachytherapy, 29.4 % have been referred for surgery and
      one patient has refused definitive treatment. CONCLUSION: Our findings to date
      support active surveillance as a valid strategy for early, localised prostate
      cancer.

PMID- 24078293
TI  - Adverse event reporting patterns of newly approved drugs in the USA in 2006: an
      analysis of FDA Adverse Event Reporting System data.
AB  - BACKGROUND: The Weber effect states that adverse event (AE) reporting tends to
      increase in the first 2 years after a new drug is placed onto the market, peaks
      at the end of the second year, and then declines. However, since the Weber effect
      was originally described, there has been improvement in the communication of
      safety information and new policies regarding the reporting of AEs by healthcare
      professionals and consumers, prompting reassessment of the existence of the Weber
      effect in the current AE reporting scenario. OBJECTIVES: To determine the AE
      reporting patterns for new molecular entity (NME) drugs and biologics approved in
      2006 and to examine these patterns for the existence of the Weber effect.
      METHODS: Publicly available FDA Adverse Event Reporting System data were used to
      assess the AE reporting patterns for a 5-year period from the drug's approval
      date. The total number of annual reports from all sources, based on the report
      date, was plotted against time (in years). RESULTS: In the period from 2006 to
      2011, a total of 91,187 AE reports were submitted for 19 NMEs approved in 2006.
      The highest number of AE reports were submitted for varenicline tartrate (N =
      47,158) and the lowest number for anidulafungin (N = 161). Anidulafungin was
      reported to have the highest proportion of death reports (36 %) and varenicline
      tartrate the lowest proportion (1.7 %). The classic Weber pattern was not
      observed for any of the 19 NMEs approved in 2006. While there was no one
      predominant pattern of AE report volume, we grouped the drugs into four general
      categories; the majority of drugs had either a continued increase in reports
      (Category A 31.6 %) or an N-pattern with reporting reaching an initial peak in
      year 2 or 3, declining and then beginning to climb again (Category B 42.1 %).
      CONCLUSIONS AND RELEVANCE: There have been numerous changes in AE reporting,
      particularly a huge increase in overall annual report volume, since the Weber
      effect was first reported. Our results suggest that a Weber-type reporting
      pattern should not be assumed in the design or interpretation of analyses based
      on AE reports.

PMID- 24078292
TI  - Effects of Passiflora nitida Kunth leaf extract on digestive enzymes and high
      caloric diet in rats.
AB  - The present study investigated inhibition of pancreatic lipase and metabolic
      effects of high caloric diet in rats. The Passiflora nitida hydroethanol leaf
      extract (PNE) was used in in vitro assays or administered to rats to study
      dyslipidemia. Inhibition of lipase in vitro was studied by a spectrophotometric
      assay using orlistat as the positive control. The effects of PNE on reduction of
      postprandial triglyceride were studied by oral fat-overloading in rats. Metabolic
      alterations were induced using the cafeteria diet and 4 weeks post-treatment with
      PNE or orlistat and blood samples were collected and biochemical analyses were
      performed. Liver and retroperitoneal fat tissues were obtained to analyze weight
      and steatosis. IC50 (lg/mL) values for pancreatic lipase inhibition were 21.2 +/-
      0.8 and 0.1 +/- 0.01 for PNE and orlistat, respectively. Oral administration of
      lipid emulsion resulted in postprandial hypertriglyceridemia at 3 h
      postadministration and when rats were then administered PNE and orlistat there
      was decreased of triglyceride levels by 15 % compared to control. Although the
      energy consumption by the cafeteria diet had been higher, there was no
      significant weight gain observed in the study groups. The cafeteria diet resulted
      in a significant increase of weight in the retroperitoneal fat and
      hypertriglyceridemia levels that could be significantly reduced by PNE and
      orlistat treatment. We hypothesized that PNE administration prevented the
      hypertriglyceridemia in rats with a high caloric diet, possibly owing to
      reduction of lipid absorption and pancreatic lipase inhibition.

PMID- 24078297
TI  - Luminescent Fluorene-Based Bis-Pyrazolyl Aniline Ligand for Aluminum Detection.
AB  - The design, synthesis, and photophysical properties of a new fluorene-based
      fluorescent chemosensor, 4-((E)-2-(2-(benzo[d]thiazol-2-yl)-9,9-diethyl-9H
      fluoren-7-yl)vinyl)-N,N-bis((3,5-dimethyl-1H-pyrazol-1-yl)methyl)benzenamine (AXF
      Al), is described for the detection of Al3+. AXF-Al exhibited absorption at 382
      nm and strong fluorescence emission at 542 nm (fluorescence quantum yield, Phi F,
      of 0.80). The capture of Al3+ by the pyrazolyl aniline receptor resulted in
      nominal change in the linear absorption (372 nm) but a large hypsochromic shift
      of 161 nm in the fluorescence spectrum (542 to 433 nm, Phi F = 0.88), from which
      Al3+ was detected both ratiometrically and colorimetrically. The addition of
      other metal ions, namely Mg2+, Ca2+, Mn2+, Fe2+, Co2+, Ni2+, Cu2+, Zn2+, Cd2+, Hg
      2+ and Pb2+, produced only minimal changes in the optical properties of this
      probe. The emission band of this probe was also accessed by two-photon excitation
      in the near-IR, as two-photon absorption (2PA) is important for potential
      applications in two-photon fluorescence microscopy (2PFM) imaging. The 2PA cross
      section of the free fluorenyl ligand AXF-Al was 220 GM at 810 nm and 235 GM at
      810 nm for the Al-ligand complex, practically useful properties for 2PFM.

PMID- 24078298
TI  - Menstrual cycle effects on attitudes toward romantic kissing.
AB  - Hormonal changes associated with the human menstrual cycle have been previously
      found to affect female mate preference, whereby women in the late follicular
      phase of their cycle (i.e., at higher risk of conception) prefer males displaying
      putative signals of underlying genetic fitness. Past research also suggests that
      romantic kissing is utilized in human mating contexts to assess potential mating
      partners. The current study examined whether women in their late follicular cycle
      phase place greater value on kissing at times when it might help serve mate
      assessment functions. Using an international online questionnaire, results showed
      that women in the follicular phase of their menstrual cycle felt that kissing was
      more important at initial stages of a relationship than women in the luteal phase
      of their cycle. Furthermore, it was found that estimated progesterone levels were
      a significant negative predictor for these ratings.

PMID- 24078299
TI  - Methylene blue does not have to be considered only as rescue therapy for
      distributive shock.

PMID- 24078302
TI  - Community pharmacists' interventions with electronic prescriptions in England: an
      exploratory study.
AB  - BACKGROUND: Prescribing errors in primary care are problematic. The electronic
      prescription service (EPS) is an English electronic system linking prescribing,
      dispensing and reimbursement, designed to rectify some of the problems associated
      with paper-based prescribing. OBJECTIVE: To document the numbers and types of
      interventions made by community pharmacists and their staff using EPS release 2
      (EPSR2), compare these with those made for other prescription types, and comment
      on potential effects of EPSR2 on pharmacy practice. METHODS: We invited staff in
      15 community pharmacies to record problems encountered arising from failures in
      prescribing, dispensing or supply systems for prescribed medication, for a 2 week
      period. RESULTS: Eight pharmacies participated, of which five used EPSR2. These
      pharmacies reported 69 problems with 68 prescriptions (median 7.5 problems per
      pharmacy, range 2-22). A total of 33 problems were clinical in nature and 6 were
      organisational or logistical in origin. Thirty unsigned prescriptions were
      reported, all non-EPSR2. Of the 69 problems, eight were primarily related to
      EPSR2 functionality. CONCLUSION: EPSR2 should reduce the number of unsigned
      prescriptions in circulation. However, prescribers should avoid the use of Latin
      abbreviations that cannot be interpreted directly by patients, and consider the
      compatibility of regularly prescribed items with the NHS dictionary of medicines
      and devices.

PMID- 24078303
TI  - Personal, Social and Environmental Risk Factors of Problematic Gambling Among
      High School Adolescents in Addis Ababa, Ethiopia.
AB  - Understanding risk factors of problematic gambling is prerequisite to effective
      intervention design to alleviate the negative consequences of gambling. This
      study explored the personal, social and environmental risk factors of problematic
      gambling in four high schools in Addis Ababa, Ethiopia, among students (N = 422)
      ranging from 12 to 21 years of age. Results from the cross-sectional survey
      showed that personal feelings (e.g., self-esteem, false perceptions about
      winning, drug abuse), social factors (e.g., peer influence, parental gambling),
      and environmental factors (e.g., accessibility of gambling venues,
      advertisements) were significant correlates of problematic gambling. The study
      also revealed that men were more at risk for severe problematic gambling than
      females. Among the identified types of gambling activities, the most prevalent
      ones were playing cards followed by flipping coin and pool gambling while
      internet gambling was among the least reported gambling activities. By
      identifying personal, social and environmental correlates of risky gambling
      activities this study provides evidence-based information for the systematic
      design and evaluation of educational interventions to prevent problematic
      gambling in young people.

PMID- 24078300
TI  - 2013 update of the 2011 American College of Rheumatology recommendations for the
      treatment of juvenile idiopathic arthritis: recommendations for the medical
      therapy of children with systemic juvenile idiopathic arthritis and tuberculosis
      screening among children receiving biologic medications.

PMID- 24078304
TI  - Validation of the Gambling Refusal Self-Efficacy Questionnaire for Chinese
      Undergraduate Students.
AB  - Although research on self-efficacy in the gambling literature took place more
      than 25 years ago, only in the recent decade did researchers attempt to develop
      valid and reliable measures of gambling-related self-efficacy. Recently Casey et
      al. (J Gambl Stud 24:229-246, 2008) developed the Gambling Refusal Self-Efficacy
      Questionnaire (GRSEQ) in an Australian sample, which is a valuable tool for
      gambling research. The first objective of this study is to validate the measure
      in a new sample. Given that previous research on Chinese's gamblers' self
      efficacy is lacking, and that related research often used ad-hoc measures of the
      construct, a second objective of this study is to evaluate whether the GRSEQ is
      suitable for Chinese people. A sample of 427 university students (56.4 % females,
      50.7 % gamblers) answered a questionnaire with measures including the GRSEQ,
      subjective norms, intentions toward gambling, general self-efficacy,
      impulsiveness, and pathological gambling symptoms. Evidence was found for the
      four-factor structure, internal consistency, criterion-related validity, and
      discriminant validity of the Chinese version of the GRSEQ among this young
      Chinese group.

PMID- 24078313
TI  - Chinese worm community made delightful wiggles in Hefei September 6 to September
      8, 2013.

PMID- 24078305
TI  - Stress signaling pathways for the pathogenicity of Cryptococcus.
AB  - Sensing, responding, and adapting to the surrounding environment are crucial for
      all living organisms to survive, proliferate, and differentiate in their
      biological niches. This ability is also essential for Cryptococcus neoformans and
      its sibling species Cryptococcus gattii, as these pathogens have saprobic and
      parasitic life cycles in natural and animal host environments. The ability of
      Cryptococcus to cause fatal meningoencephalitis is highly related to its
      capability to remodel and optimize its metabolic and physiological status
      according to external cues. These cues act through multiple stress signaling
      pathways through a panoply of signaling components, including receptors/sensors,
      small GTPases, secondary messengers, kinases, transcription factors, and other
      miscellaneous adaptors or regulators. In this minireview, we summarize and
      highlight the importance of several stress signaling pathways that influence the
      pathogenicity of Cryptococcus and discuss future challenges in these areas. 

PMID- 24078312
TI  - Organic trace mineral levels in the first 96-h post-hatch impact growth
      performance and intestinal gene expression in broiler chicks.
AB  - Alterations in nutrient intake in the avian neonatal posthatch period can impact
      development, performance, and metabolism in adulthood. Very little is known about
      how mineral levels during the post-hatch period affect or "program" gene
      expression patterns later in life. The objective of this study was to determine
      the effect of post-hatch (0 to 96 h) dietary mineral supplementation on
      performance, tissue mineral content, and intestinal gene expression profiles in
      21-day-old broiler chicks. One-day-old chicks were randomly assigned to one of
      two treatment groups consisting of N (organic Zn, Cu, and Mn provided at 100 % of
      recommendations (National Research Council 1994)) and/or L (organic Zn, Cu, and
      Mn provided at 20 % of recommendations (National Research Council 1994)) diets
      fed in two intervals (days 1-4, days 5-21) as follows: (1)N-Lor (2)L-L.
      Performance parameters did not differ between treatments except that body weight
      gain was greater (P < 0.05) in L-L birds than N-L birds over the experimental
      period. Bone mineral content was similar for both treatments at day 21.
      Intestinal gene expression profiling was examined using the Affymetrix GeneChip
      Chicken genome array. Ingenuity pathway analysis revealed differences in gene
      expression profiles between N and L treatments at day 5. At day 21, profiles were
      unique between N-L and L-L, suggesting that the diet fed until day 4 had an
      impact on gene expression patterns at day 21 even when birds were fed the same
      diets day 5-day 21. In this study, we demonstrated that diets fed for the 96 h
      post-hatch had long-term effects on gene expression, providing unique information
      as to why post-hatch diets are so important for the longterm bird health and
      productivity.

PMID- 24078306
TI  - The Taz1p transacylase is imported and sorted into the outer mitochondrial
      membrane via a membrane anchor domain.
AB  - Mutations in the mitochondrial transacylase tafazzin, Taz1p, in Saccharomyces
      cerevisiae cause Barth syndrome, a disease of defective cardiolipin remodeling.
      Taz1p is an interfacial membrane protein that localizes to both the outer and
      inner membranes, lining the intermembrane space. Pathogenic point mutations in
      Taz1p that alter import and membrane insertion result in accumulation of
      monolysocardiolipin. In this study, we used yeast as a model to investigate the
      biogenesis of Taz1p. We show that to achieve this unique topology in
      mitochondria, Taz1p follows a novel import pathway in which it crosses the outer
      membrane via the translocase of the outer membrane and then uses the Tim9p-Tim10p
      complex of the intermembrane space to insert into the mitochondrial outer
      membrane. Taz1p is then transported to membranes of an intermediate density to
      reach a location in the inner membrane. Moreover, a pathogenic mutation within
      the membrane anchor (V224R) alters Taz1p import so that it bypasses the Tim9p
      Tim10p complex and interacts with the translocase of the inner membrane, TIM23,
      to reach the matrix. Critical targeting information for Taz1p resides in the
      membrane anchor and flanking sequences, which are often mutated in Barth syndrome
      patients. These studies suggest that altering the mitochondrial import pathway of
      Taz1p may be important in understanding the molecular basis of Barth syndrome. 

PMID- 24078314
TI  - Fatalism and cancer risk knowledge among a sample of highly acculturated Latinas.
AB  - Fatalistic beliefs about cancer are associated with decreased likelihood of
      knowing about cancer risk factors and engaging in cancer prevention and screening
      behaviors. Research suggests that Latinas are especially likely to hold
      fatalistic beliefs. However, this research has been in less-acculturated, high
      poverty convenience samples. This study examined cancer knowledge, cancer
      fatalism, and the association between fatalism and knowledge in a national sample
      of highly acculturated, middle-income Latinas (N = 715). Results indicate that
      cancer fatalism is pervasive, and knowledge about cancer risk factors is lacking
      among this population. Fatalistic beliefs are paradoxically associated with
      cancer knowledge. Opportunities for tailored communications to improve health
      behaviors and additional research to understand causes/effects of these findings
      are discussed in the context of a growing body of research about how to
      communicate health information to more-acculturated Latinos.

PMID- 24078315
TI  - An evaluation of a community-academic-clinical partnership to reduce prostate
      cancer disparities in the South.
AB  - Engaging partners in the planning, implementation, and evaluation of cancer
      education programs is critical for improving the health of our communities. A 2
      year pilot education intervention on prostate cancer decision making and
      participation in medical research was funded by the National Cancer Institute.
      The partnership involving community members and clinical staff at a cancer center
      was used to develop recruitment strategies and plan for the implementation of the
      intervention with African-American middle-age and older men and female family
      members. We assessed partners' perceptions of this community-academic-clinical
      research collaboration. In year 2, eight project advisory council members were
      selected among existing partners and year 1 participants to serve as a formal
      committee. Council members were required to participate in telephone and in
      person meetings and actively support recruitment/implementation efforts. At the
      conclusion of the project, 20 individuals (all clinical and community partners,
      including the eight advisory council members) were invited to complete a survey
      to assess their perceived impact of the collaboration on the community and
      provide suggestions for future collaborations. Most partners agreed that their
      organization benefitted from the collaboration and that various aspects of the
      advisory council process (e.g., both formal and informal communication) worked
      well. The most noted accomplishment of the partnership related to leveraging the
      collaboration to make men more knowledgeable about prostate cancer decision
      making. Suggested improvements for future collaborations included distributing
      more frequent updates regarding project successes. Evaluating partners'
      perceptions of this collaboration provided important recommendations for future
      planning, implementation, and evaluation of community-based cancer education
      programs.

PMID- 24078316
TI  - The role of bariatric surgery in the treatment of type 2 diabetes: current
      evidence and clinical guidelines.
AB  - The incidence of type 2 diabetes (T2D) continues to rise worldwide. The
      management of T2D is challenging and therefore amenable to multimodality
      treatment options. Many published observations of obese individuals with T2D that
      have undergone bariatric surgery consistently demonstrate remarkable improvement
      and short-term remission of T2D. Recently published randomized trials confirm
      these findings and demonstrate significantly improved glycemic control following
      bariatric procedures, especially Roux-en-Y gastric bypass and laparoscopic sleeve
      gastrectomy. However, the question of long-term remission remains uncertain.
      Clinicians may consider the use of bariatric surgery as a treatment option for
      certain obese patients with T2D who have failed intensive lifestyle intervention
      and conventional pharmacotherapy. 

PMID- 24078317
TI  - Preventing type 2 diabetes, CVD, and mortality: surgical versus non-surgical
      weight loss strategies.
AB  - The burden of type 2 diabetes is increasing. The prevention of the disease,
      improvement of metabolic control, and more importantly reduction in mortality
      remain a challenge for primary care doctors, diabetologists, researchers and
      policymakers. In this article, the available literature is reviewed with a focus
      on recent developments. Comparison between medical and surgical interventions is
      performed using mainly head-to-head trials where possible. Weight loss surgery is
      effective for glycaemic control. The need for level 1 data with hard end points
      such as cardiovascular risk and mortality is highlighted, and the prospect of the
      combination of existing therapy options is emphasized. 

PMID- 24078318
TI  - Elevated white blood cell counts in Cushing's disease: association with
      hypercortisolism.
AB  - BACKGROUND: Glucocorticoid receptors are expressed in white blood cells (WBC's)
      and are known to play a role in cell adhesion and WBC's recruitment from bone
      marrow. In Cushing's disease leukocytosis is frequently mentioned as laboratory
      finding. However, there is no data on the prevalence of this finding among
      patients, or correlation with disease severity. PURPOSE: To investigate the
      prevalence of leukocytosis in patients with Cushing's disease, alterations in
      other blood count parameters and correlation with degree of hypercortisolism.
      METHODS: Data of 26 patients diagnosed and followed for Cushing's disease at our
      clinic was reviewed. Two patients had disease relapse after complete remission
      and were studied as 2 separate events. RESULTS: Of the 26 patients, 17 were women
      (71 %), with a mean age of 39.8 +/- 12.7 years. Mean baseline WBC count was
      10,500 +/- 2,600 cells/MUl and dropped to 8,400 +/- 1,900 cells/MUl (p < 0.05)
      after treatment, mean neutrophil count at baseline was 7,600 +/- 2,600 cells/MUl
      and dropped to 5,300 +/- 1,700 cells/MUl (p < 0.05), lymphocyte count was 2,000
      +/- 600 cells/MUl and raised to 2,300 +/- 600 cells/MUl (p < 0.05), hemoglobin
      was 13.7 +/- 1.2 g/dl and dropped to 12.8 +/- 1.4 g/dl (p < 0.05), and platelet
      number did not change. Elevated WBC count was present in 11/28 cases (40 %).
      Those patients with normal baseline WBC (mean 9,000 +/- 1,500 cells/MUl) dropped
      also to 7,700 +/- 1,300 cells/MUl after treatment (p < 0. 05). There was a
      significant positive correlation between decrease in UFC secretion and change in
      WBC's following treatment (r = 0.67, p < 0.01). CONCLUSIONS: Patients with
      Cushing's disease present with leukocytosis in approximately 40 % of cases. In
      most cases, including those without elevated baseline count, the WBC's decreased
      with disease remission, demonstrating the effect of glucocorticoids on these
      blood cells.

PMID- 24078319
TI  - Second attempt to withdraw cabergoline in prolactinomas: a pilot study.
AB  - PURPOSE: According to Pituitary and Endocrine Society recommendations,
      cabergoline (CAB) therapy can be discontinued after 2 years in hyperprolactinemic
      patients who fit certain criteria. Previous studies found recurrence rates
      ranging between 26 and 69 %. Whether CAB therapy can be successfully discontinued
      after one unsuccessful withdrawal is unknown. METHODS: We conducted a pilot
      prospective two-center study on a second attempt of CAB withdrawal. Inclusion
      criteria were: (1) recurrence of hyperprolactinemia after first withdrawal; (2)
      additional CAB therapy for at least 2 years; (3) normal serum prolactin; (4) CAB
      dose <= 1 mg/week. Prolactin level was monitored after discontinuing therapy.
      Median follow up for patients who are still in remission was 42 months (range =
      24-60). RESULTS: A total of 17 patients were recruited. Mean age was 41.0 +/-
      17.3 years. 65 % were female. Initial tumors were microadenoma in 64.7 %, and
      macroadenoma in 35.3 %. The average weekly CAB dose at second withdrawal was 0.38
      +/- 0.20 mg (median = 0.25, range = 0.175-1). Eleven of 17 patients (64.7 %)
      recurred. Median time to recurrence was 6 months. The incidence of recurrence was
      44 events per 100 person-years. The estimated cumulative hazard of recurrence was
      40 and 82 % at 6 and 12 months respectively. The probability to be recurrence
      free at 6 and 12 months was 65 and 41 %, respectively. CONCLUSIONS: Second
      attempt of CAB withdrawal after 2 additional years of therapy may be successful
      in some patients. A second withdrawal can be attempted with close monitoring of
      prolactin level. In this study, we could not identify any predictor of
      recurrence. Most of the recurrences occurred within the first 12 months after
      withdrawal.

PMID- 24078320
TI  - An animal PET scanner using flat-panel position-sensitive PMTs.
AB  - OBJECTIVE: To design, build, and evaluate an animal PET scanner, which can be
      used with non-human primates under conscious condition, incorporating flat-panel
      position-sensitive photomultiplier tubes (PS-PMTs). METHODS: The system contains
      30 detector modules, each having two PS-PMTs and 16*18 lutetium-yttrium oxyortho
      silicate scintillation crystal arrays. The system has 17,280 crystals (480 per
      ring) arranged in 36 rings, with a diameter of 508 mm and axial extent of 108 mm.
      The gantry tilt mechanism enables PET studies to be performed on a monkey in the
      sitting position. Data can be acquired in either the 2D or 3D mode, with the
      slice collimators being retracted in the 3D mode. RESULTS: At the center of the
      field-of-view, radial resolution is 2.7 mm full width at half maximum (FWHM) and
      tangential resolution is 2.4 mm FWHM, while axial resolution is 2.5 mm FWHM for
      direct slices and 2.7 mm FWHM for cross slices. Scatter fraction, count rate
      capability, and sensitivity were evaluated using a cylindrical phantom 10 cm in
      diameter. The noise equivalent count rate in the 3D mode is equivalent to that in
      the 2D mode at a three times higher radioactivity level. Total system sensitivity
      is 1.3 kcps/(kBq/mL) in 2D mode and 7.4 kcps/(kBq/mL) in the 3D mode. Animal
      studies with a monkey were performed to evaluate the imaging capabilities of the
      scanner. CONCLUSION: The new PET scanner will be a useful research tool with non
      human primates for pre-clinical drug development.

PMID- 24078321
TI  - Predictors of cervical cancer screening among Vietnamese American women.
AB  - This study examines Pap testing behavior among 265 Vietnamese American women aged
      18 or above. A community-based survey was conducted with Vietnamese women in five
      cities: Houston (TX), Springfield (MA), Camden (NJ), Charlotte (NC), and Falls
      Church (VA). Seventy-five percent of the study sample ever received a Pap test,
      45% within the last 12 months. Women's perceived risks of cancer, belief that
      cancer can be detected early with screening, and disagreement that it is
      embarrassing to get tested and that only married women should get tested are
      related to Pap testing. Having health insurance is the most important predictor
      of Pap testing. Main reasons for not having tested in the last 12 months include:
      feeling well, having no insurance, and high costs. Interventions should improve
      financial access to Pap testing among Vietnamese American women. Results also
      suggest that future communication programs should emphasize preventive practices
      and change traditional attitudes and misconceptions related to Pap testing.

PMID- 24078325
TI  - High concentration of gadolinium ion modifying isolated rice mitochondrial
      biogenesis.
AB  - Mitochondria play an important role in plant growth and development, cooperating
      with the endoplasmic reticulum and nucleus. Gadolinium, one of the rare earth
      elements, is an inhibitor of stretch-activated calcium channels located on the
      endoplasmic reticulum and plasma membrane and has no effect on nuclear calcium
      variation in plant cells. We analyzed the effects of Gd3+ on mitochondria
      function by monitoring mitochondrial swelling, changes of membrane fluidity, and
      transmembrane potential collapse and by observing mitochondrial ultrastructure.
      We found that high concentration of Gd3+ induces rice mitochondrial dysfunction
      through mitochondrial permeability transition (MPT). The protection of DTT and
      EDTA demonstrate that Gd3+ blocks the inner membrane ion channel through thiol
      chelation.

PMID- 24078326
TI  - Analysis of immune-relevant genes expressed in spleen of Capra hircus kids fed
      with trivalent chromium.
AB  - Chromium is a biologically important element for humans and laboratory animals.
      Although the favorable effects of trivalent chromiumon immune responses of
      studied animals have been well documented, the precise mechanisms by which the
      chromium acts on immune system is relatively poor studied. In this study, real
      time qPCR technique was employed to evaluate the expression profiles of four
      immune-related genes (B2M, MHCA, MHCB, and Rap2A) in spleens of the domestic
      goats, Capra hircus, feeding on four different levels of supplemental chromium
      (0, 0.5, 1, and 1.5 mg/day) as chromium- methionine. The results showed that 1.5
      mg/day of supplemental chromium significantly increased the expression of the
      four studied genes (P <0.01). Since the studied genes play important roles in
      development, activation, and migration of lymphocytes, their increased expression
      seems to be an unknown mechanism by which chromium impose reinforcing effects on
      immune system. Therefore, supplemental chromium can be potentially used to
      improve immune responses especially in animals experiencing any type of stress
      such as invasion by a pathogen.

PMID- 24078327
TI  - Metabolism, intake, and digestibility of lambs supplemented with organic
      chromium.
AB  - The aim of the present study was to evaluate the metabolism of organic chromium
      and its effect on digestibility and intake of lambs. Four 4-month-old male lambs,
      each weighing 28 kg, were used. The animals were kept in metabolic cages for a
      period of 20 days (15 days of adaptation and 5 days of experimentation), in two
      experimental phases, with inverted treatments. Organic chromium was administered
      by intraruminal infusion of 1 mg of chromium-rich yeast (Saccharomyces
      cerevisiae) throughout the adaptive and experimental period. The dry material
      rates of the diet and feces of the animals were evaluated to estimate
      consumption, digestibility, and fecal production. During the experimental period,
      blood, feces, and urine were collected every 24 h to determine chromium levels.
      There was no significant difference in the excretion of chromium in the urine,
      and no mineral remnants were detected in the blood. Excretion was generally
      fecal. There was greater excretion of chromium in the feces of lambs in the
      treated group on day 0 and day 3, compared with the control group. The use of
      organic chromium promoted an increase in the consumption of dry material in the
      treated animals only at day 0 (P <0.05). The production of fecal dry matter was
      greater among the treated lambs than among the animals of the control group on
      day 1, day 2, day 3, and day 4 (P <0.05). The results obtained showed that
      organic chromium associated with live yeasts is not absorbed by the body and do
      not affect the intake time in the dose used.

PMID- 24078328
TI  - Journal clubs: an educational approach to advance understanding among community
      partners and academic researchers about CBPR and cancer health disparities.
AB  - Journal clubs may enhance the knowledge and skills necessary to engage in
      community-based participatory research (CBPR) that will ultimately impact cancer
      health disparities. This article (1) describes an innovative approach to adapting
      the traditional journal club format to meet community and academic participants'
      needs, (2) presents evaluation data, and (3) explores whether responses differed
      between academic and community members. Five journal clubs occurred between
      February 2011 and May 2012 as a training activity of a regional cancer health
      disparities initiative. Each journal club was jointly planned and facilitated by
      an academic member in collaboration with a community partner. Attendees were
      recruited from academic programs across the Moffitt Cancer Center/University and
      community partners. Responses to a 13-item evaluation of each journal club
      session were compared to assess whether certain topics were evaluated more
      favorably, and explore differences between academic and community participants'
      assessment of the topic relevance. Evaluations were positive (mean ratings >4 out
      of 5) on most items and overall. No statistically significant differences were
      observed between academic and community members' ratings. Key overlapping
      interests by community partners and academic researchers/trainees for future
      journal club topics included discussing real-world CBPR examples and methods for
      involving the community in research. Although the initial goal was to use journal
      clubs as an educational tool to increase CBPR knowledge and skills of junior
      faculty trainees, results suggest mutual academic-community benefit and interest
      in learning more about CBPR as a way to reduce cancer health disparities.

PMID- 24078329
TI  - Pathogenic LRRK2 mutations in nuclear ageing--a new organelle to study in
      Parkinson's disease.

PMID- 24078330
TI  - Restoring impaired protein metabolism in Parkinson's disease--TFEB-mediated
      autophagy as a novel therapeutic target.

PMID- 24078331
TI  - Commentary.

PMID- 24078332
TI  - Walking speed and health-related quality of life in multiple sclerosis.
AB  - OBJECTIVE: The aim of this study was to evaluate the association between slower
      walking and health-related quality of life (HRQoL) in multiple sclerosis (MS)
      patients. METHODS: We used North American Research Committee on Multiple
      Sclerosis data to conduct a study of participants completing both the regular
      semiannual and supplemental spring 2010 surveys. Question 10 of the 12-item
      Multiple Sclerosis Walking Scale ("How much has your MS slowed down your
      walking?") was used to assess patient-perceived impact of walking speed on
      HRQoL.HRQoL assessments included the Short Form-12 (SF-12),EuroQoL-5 Dimension
      (EQ-5D), Short Form-6 Dimension(SF-6D), and a visual analog scale (VAS). RESULTS:
      A total of 3,670 registrants completed both surveys and were included. Unadjusted
      analyses showed that compared with those classifying the impact of MS on walking
      speed as "not at all" (n = 661), participants stating MS impacted their walking
      speed "a little" (n = 722), "moderately" (n = 486), "quite a bit" (n = 714), and
      "extremely" (n = 1,087) reported poorerSF-12 physical component scale (PCS) (r = 
      0.69,p?0.001), mental component scale (MCS) (r = -0.16,p?0.001), and health
      status index scores (r = -0.50 to-0.51 for the EQ-VAS, EQ-5D and SF-6D, p?0.001
      for all). After adjustment for demographics and additional MS related disability
      and symptoms, the impact of walking speed remained significant, although less
      profound for the PCS (reductions of 3.59 -12.31 across walking speed
      classifications)and index scores (reductions ranging from 1.98 to 14.06, 0.04 to
      0.13, and 0.02 to 0.07 for the EQ-VAS,EQ-5D, and SF-6D). Reduction in walking
      speed was no longer associated with a worse MCS (p[0.05 all classifications of
      walking speed). CONCLUSION: Incremental decrements in HRQoL were observed as
      patients perceived greater levels of reduction in their walking speed.

PMID- 24078333
TI  - Increased bone fractures among elderly United States hemodialysis patients.
AB  - BACKGROUND: Fractures are an important cause of morbidity in hemodialysis
      patients. Multiple advances in the treatment of mineral and bone disease in
      hemodialysis patients have occurred. The purpose of this study was to determine
      whether the rate of fractures in hemodialysis patients has changed over time.
      METHODS: We studied US Renal Data System (USRDS) datasets to determine the rates
      of hospitalized fractures among hemodialysis patients. The primary outcome was
      incidence of fractures requiring hospitalization. The fracture rate per 1000
      person-years was calculated by year from 1992 to 2009. The first 90 days after
      initiating dialysis were excluded from analysis. RESULTS: The incidence of hip
      and vertebral fractures increased from 12.5 fractures per 1000 patient-years in
      1992 to 25.3 per 1000 patient-years in 2004 (P < 0.0001). Arm and leg fractures
      increased from 3.2 per 1000 patient-years in 1992 to 7.7 per 1000 patient-years
      in 2009 (P < 0.0001). The greatest increase in hip and verterbral fracture rate
      was seen in white patients >65 years of age. After 2004, the incidence rate of
      these fractures stabilized and subtly declined, but did not decrease
      significantly. CONCLUSIONS: Fracture rates increased significantly in
      hemodialysis patients from 1992 to 2004, with most of the increase occurring in
      elderly white patients. Assessment of fracture risk and management in dialysis
      patients at greatest risk requires greater emphasis and further study.

PMID- 24078334
TI  - Postprandial responses of incretin and pancreatic hormones in non-diabetic
      patients with end-stage renal disease.
AB  - BACKGROUND: Patients with end-stage renal disease (ESRD) have glucometabolic
      disturbances resulting in a high prevalence of prediabetes. The underlying
      pathophysiology remains unclear, but may prove important for the strategies
      employed to prevent progression to overt diabetes. Meal-induced release of the
      insulinotropic gut-derived incretin hormones and pancreatic hormones play a
      critical role in the maintenance of a normal postprandial glucose tolerance.
      METHODS: We studied patients with ESRD and either normal (n = 10) or impaired (n
      = 10) glucose tolerance, and control subjects (n = 11). Plasma concentrations of
      glucose, insulin, glucagon, glucagon-like peptide-1 (GLP-1), glucose-dependent
      insulinotropic polypeptide (GIP) and paracetamol were measured repeatedly during
      a standardized 4-h liquid meal including 1.5 g paracetamol (added for evaluation
      of gastric emptying). RESULTS: Fasting glucose and postprandial glucose responses
      were comparable between groups (P > 0.082). Patients with ESRD exhibited higher
      fasting levels of GIP and glucagon compared with controls (P < 0.001). Baseline
      corrected GLP-1 and glucagon responses were enhanced (P < 0.002), baseline
      corrected insulin responses and insulin excursions were reduced (P < 0.035), and
      paracetamol excursions were delayed (P < 0.024) in patients with ESRD compared
      with controls. None of the variables differed between the two ESRD subgroups.
      CONCLUSIONS: Non-diabetic patients with ESRD were characterized by reduced
      postprandial insulin responses despite increased secretion of the insulinotropic
      incretin hormone GLP-1. Fasting levels and baseline-corrected responses of
      glucagon were elevated and gastric emptying was delayed in the ESRD patients.
      These perturbations seem to be caused by uraemia per se and may contribute to the
      disturbed glucose metabolism in ESRD patients.

PMID- 24078335
TI  - Effects of daily hemodialysis on heart rate variability: results from the
      Frequent Hemodialysis Network (FHN) Daily Trial.
AB  - BACKGROUND: End-stage renal disease is associated with reduced heart rate
      variability (HRV), components of which generally are associated with advanced
      age, diabetes mellitus and left ventricular hypertrophy. We hypothesized that
      daily in-center hemodialysis (HD) would increase HRV. METHODS: The Frequent
      Hemodialysis Network (FHN) Daily Trial randomized 245 patients to receive 12
      months of six versus three times per week in-center HD. Two hundred and seven
      patients had baseline Holter recordings. HRV measures were calculated from 24-h
      Holter electrocardiograms at both baseline and 12 months in 131 patients and
      included low-frequency power (LF, a measure of sympathetic modulation), high
      frequency power (HF, a measure of parasympathetic modulation) and standard
      deviation (SD) of the R-R interval (SDNN, a measure of beat-to-beat variation).
      RESULTS: Baseline to Month 12 change in LF was augmented by 50% [95% confidence
      interval (95% CI) 6.1-112%, P =0.022] and LF + HF was augmented by 40% (95% CI
      3.3-88.4%, P = 0.03) in patients assigned to daily hemodialysis (DHD) compared
      with conventional HD. Changes in HF and SDNN were similar between the randomized
      groups. The effects of DHD on LF were attenuated by advanced age and diabetes
      mellitus (predefined subgroups). Changes in HF (r = -0.20, P = 0.02) and SDNN (r
      = -0.18, P = 0.04) were inversely associated with changes in left ventricular
      mass (LVM). CONCLUSIONS: DHD increased the LF component of HRV. Reduction of LVM
      by DHD was associated with increased vagal modulation of heart rate (HF) and with
      increased beat-to-beat heart rate variation (SDNN), suggesting an important
      functional correlate to the structural effects of DHD on the heart in uremia.

PMID- 24078336
TI  - The emerging epidemic of heart failure with preserved ejection fraction.
AB  - Heart failure with preserved ejection fraction (HFpEF), which currently
      represents approximately 50 % of heart failure (HF) cases, is common and
      associated with high morbidity and mortality. Understanding the epidemiology of
      HFpEF has been difficult due to the challenges in HFpEF diagnosis and the
      heterogeneous etiologies and pathophysiologies that underlie HFpEF. Nevertheless,
      several high-quality epidemiology and observational registry studies of HFpEF
      demonstrate that an increasing prevalence of HFpEF in both the outpatient and
      inpatient settings, coupled with a lack of evidence-based effective treatments
      for HFpEF, is resulting in an emerging epidemic of HFpEF. In this review, we
      discuss the emerging HFpEF epidemic, focusing on: (1) reasons for the rising
      prevalence of HFpEF; (2) the abnormalities in cardiac structure and function that
      dictate the transition from risk factors to HFpEF; (3) novel HFpEF mechanisms
      that may underlie the increase in HFpEF prevalence; (4) prognosis of HFpEF; and
      (5) risk prediction in HFpEF. We conclude with 10 unanswered questions onHFpEF
      epidemiology thatwill be important areas for future investigation.

PMID- 24078338
TI  - Gene coexpression as Hebbian learning in prokaryotic genomes.
AB  - Biological interaction networks represent a powerful tool for characterizing
      intracellular functional relationships, such as transcriptional regulation and
      protein interactions. Although artificial neural networks are routinely employed
      for a broad range of applications across computational biology, their underlying
      connectionist basis has not been extensively applied to modeling biological
      interaction networks. In particular, the Hopfield network offers nonlinear
      dynamics that represent the minimization of a system energy function through
      temporally distinct rewiring events. Here, a scaled energy minimization model is
      presented to test the feasibility of deriving a composite biological interaction
      network from multiple constituent data sets using the Hebbian learning principle.
      The performance of the scaled energy minimization model is compared against the
      standard Hopfield model using simulated data. Several networks are also derived
      from real data, compared to one another, and then combined to produce an
      aggregate network. The utility and limitations of the proposed model are
      discussed, along with possible implications for a genomic learning analogy where
      the fundamental Hebbian postulate is rendered into its genomic equivalent: Genes
      that function together junction together.

PMID- 24078337
TI  - Heart failure in children in tropical regions.
AB  - With the ever increasing younger population in tropical countries, the number of
      children with heart failure is increasing. However, the etiology of heart failure
      in this region varies considerably from that in the temperate region, with
      infectious causes leading the list. In this review, we have summarized the
      important causes of heart failure seen in the pediatric population in tropical
      regions.

PMID- 24078342
TI  - Long-term results of pulmonary vein antrum isolation in patients with atrial
      fibrillation: an analysis in regards to substrates and pulmonary vein
      reconnections.
AB  - AIMS: To examine the impact of left atrial (LA) low-voltage zones (LVZs) on
      atrial fibrillation (AF) recurrence after pulmonary vein antrum isolation (PVAI)
      without LA substrate modification. METHODS AND RESULTS: Seventy-six patients with
      AF (paroxysmal/persistent 65/11) were prospectively enroled. Left atrial voltage
      maps were constructed during sinus rhythm using NavX to identify LVZs (<0.5 mV),
      and PVAI without any LA substrate modification was performed using an open
      irrigation catheter. After PVAI, 20 mg of adenosine triphosphate (ATP) was
      injected. Adenosine triphosphate-induced PV reconnections were eliminated by
      touch-up ablation when unmasked. Voltage maps revealed LVZs in 24 patients (32%)
      and no LVZs in 52 (68%). During 24 +/- 7 months of follow-up, 15 patients (63%)
      with LVZs and 10 (19%) without had AF recurrences off antiarrhythmic drugs (log
      rank P < 0.001). A multivariate logistic regression analysis revealed that LVZ
      areas [odds ratio (OR): 1.12 per 1 cm(2), 95% confidence interval (CI): 1.04
      1.23, P = 0.001] and ATP-induced reconnection (OR: 2.08, 95% CI: 1.01-4.91, P =
      0.046) were significant predictors of recurrence. In those with LVZs, the LVZ
      area was strongly correlated with the LA body volume (r = 0.81, P < 0.001) and a
      unique predictor of recurrence (OR: 1.17 per 1 cm(2), 95% CI: 1.01-1.55, P =
      0.031), while in those without an LVZ, ATP-induced PV reconnection was a unique
      predictor (OR: 3.24, 95% CI: 1.15-15.39, P = 0.025). CONCLUSION: The LVZ area was
      an independent predictor of recurrence after PVAI without any LA substrate
      modification. Adenosine triphosphate-induced PV reconnection was also an
      independent predictor, especially in those without LVZs.

PMID- 24078339
TI  - Isolation and functional characterization of a tau-cadinol synthase, a  new
      sesquiterpene synthase from Lavandula angustifolia.
AB  - In this paper we characterize three sTPSs: a germacrene D (LaGERDS), a (E)-beta
      caryophyllene (LaCARS) and a tau-cadinol synthase (LaCADS). tau-cadinol synthase
      is reported here for the first time and its activity was studied in several
      biological models including transiently or stably transformed tobacco species.
      Three dimensional structure models of LaCADS and Ocimum basilicum gamma-cadinene
      synthase were built by homology modeling using the template structure of
      Gossypium arboreum delta-cadinene synthase. The depiction of their active site
      organization provides evidence of the global influence of the enzymes on the
      formation of tau-cadinol: instead of a unique amino-acid, the electrostatic
      properties and solvent accessibility of the whole active site in LaCADS may
      explain the stabilization of the cadinyl cation intermediate. Quantitative PCR
      performed from leaves and inflorescences showed two patterns of expression.
      LaGERDS and LaCARS were mainly expressed during early stages of flower
      development and, at these stages, transcript levels paralleled the accumulation
      of the corresponding terpene products (germacrene D and (E)-beta-caryophyllene).
      By contrast, the expression level of LaCADS was constant in leaves and flowers.
      Phylogenetic analysis provided informative results on potential duplication
      process leading to sTPS diversification in lavender.

PMID- 24078343
TI  - 'Preferred' management of atrial fibrillation in Europe.

PMID- 24078344
TI  - Thulium ion promotes apoptosis of primary mouse bone marrow stromal cells.
AB  - Bone is one of the main target organs for the lanthanides (Ln). Biodistribution
      studies of Tm-based compounds in vivo showed that bone had significant uptake.
      But the effect of Tm(3+) on primary mouse bone marrow stromal cells (BMSCs) has
      not been reported. So we investigated the effect and underlying mechanisms of
      Tm(3+) on BMSCs. Cell viability, cell apoptosis, reactive oxygen species (ROS)
      level, lactate dehydrogenase (LDH) activity and mitochondrial membrane potential
      (MMP) were studied. The results indicated that Tm(3+) increased the viability of
      BMSCs at concentrations of 1*10(-7), 1*10(-6), 1*10(-5), and 1*10(-4) mol/L in a
      dose-dependent manner, turned to decrease the viability of BMSCs at the highest
      concentration of 1*10(-3) mol/L for 24, 48, and 72 h. Tm(3+) at 1*10(-3) mol/L
      promoted apoptosis of BMSCs, increased the ROS and LDH levels, and decreased MMP
      in BMSCs. Taken together, we demonstrated that Tm(3+) + at 1*10(-3) mol/L might
      induce cellular apoptosis through mitochondrial pathway. These resultsmay be
      helpful for more rational application of Tm-based compounds in the future.

PMID- 24078345
TI  - Exploring prostate cancer literacy and family cancer awareness in college
      students: getting ahead of the curve in cancer education.
AB  - Cancer literacy and family cancer experiences have not been widely researched
      from the perspective of young adults. This study examined health literacy related
      to prostate cancer and family cancer awareness among a sample of 146 male and
      female college students. Results supported conventional wisdom that males would
      be more knowledgeable about the anatomical location of the prostate as compared
      to females. More notably, across the sample participants had limited knowledge of
      comprehensive prostate cancer screening but were generally aware of the prostate
      specific antigen blood test, as well as age and diet as risk factors for prostate
      cancer. Emerging associations between sexual health history and prostate cancer
      risk were not widely known by the sample as a whole and perceived availability of
      prostate health education in college was low. Finally, gender differences in
      family communication about cancer and racial differences in the number of family
      members with cancer were observed, which could have implications for perpetuating
      existing gender and racial gaps in health literacy and cancer awareness. A
      lifespan approach to cancer education research is suggested to identify ways to
      promote lifelong learning about cancer, promote prevention behaviors and informed
      screening in young adulthood, and beyond and better prepare adults to face a
      family or personal cancer diagnosis should that occur in the future.

PMID- 24078346
TI  - Implementing a one-on-one peer support program for cancer survivors using a
      motivational interviewing approach: results and lessons learned.
AB  - Peer Connect matches cancer survivors and caregivers (guides) with those
      currently experiencing cancer-related issues seeking support (partners).
      Motivational interviewing (MI)-based communication skills are taught to provide
      patient-centered support. There is little guidance about MI-based applications
      with cancer survivors who may have multiple coping needs. This paper addresses
      the results and lessons learned from implementing Peer Connect. Thirteen cancer
      survivors and two caregivers received a 2-day MI, DVD-based training along with
      six supplemental sessions. Nineteen partners were matched with guides and
      received telephone support. Evaluation included guide skill assessment
      (Motivational Interviewing Treatment Integrity Code) and 6-month follow-up
      surveys with guides and partners. Guides demonstrated MI proficiency and
      perceived their training as effective. Guides provided on average of five calls
      to each partner. Conversation topics included cancer fears, family support needs,
      coping and care issues, and cancer-related decisions. Partners reported that
      guides provided a listening ear, were supportive, and nonjudgmental. Limited time
      availability of some guides was a challenge. MI can provide support for cancer
      survivors and caregivers without specific behavioral concerns (e.g., weight and
      smoking). An MI support model was both feasible and effective and can provide
      additional support outside of the medical system.

PMID- 24078347
TI  - Genetic markers for cardiovascular disease in psoriasis: the missing piece.
AB  - Psoriasis is a common, chronic inflammatory disease associated with serious
      comorbidities. Severe psoriasis has been associated with increase cardiovascular
      mortality, due to a higher prevalence of traditional cardiovascular risk factors
      such as diabetes, hypertension, dyslipidemia and obesity, and premature
      atherosclerosis, as a consequence of its systemic inflammation. It is likely that
      there are genetic links between psoriasis, its comorbidities and cardiovascular
      disease. Although there are some studies performed in rheumatoid arthritis
      reporting some gene polymorphisms that may be associated with cardiovascular
      diseases and comorbidities these studies are lacking in psoriasis. Recognizing
      genetic markers that could predict which patients are at risk of developing
      psoriasis-linked cardiovascular comorbidities would facilitate screening
      strategies and permit an earlier management of cardiovascular risk factors, with
      important clinical implications.

PMID- 24078348
TI  - An analysis of polymorphisms within the Wnt signaling pathway in relation to
      ovarian cancer risk in a Polish population.
AB  - BACKGROUND AND OBJECTIVE: The Wnt/beta-catenin signaling pathway has been
      considered to be a factor in the development and progression of ovarian cancer.
      METHODS: All patients with ovarian cancer and controls were tested for BRCA1
      mutations (5382incC, C61G, 4153delA) with HybProbe assays and for BRCA2 mutation
      (5946delT) using high-resolution melting curve analysis (HRM). Mutation carriers
      were excluded from the association analysis. We studied nine single nucleotide
      polymorphisms (SNPs) located in CTNNB1 (beta-catenin) [rs4533622, rs2953], APC
      (rs11954856, rs351771, rs459552), and AXIN2 (rs4074947, rs7224837, rs3923087,
      rs2240308) in women with ovarian cancer without BRCA1/BRCA2 mutations (n = 228)
      and controls (n = 282). Genotyping of CTNNB1 rs4533622, rs2953, APC rs351771,
      AXIN2 rs4074947, rs3923087, and rs2240308 was performed by HRM, while that of APC
      rs11954856, rs459552 and AXIN2 rs7224837 was conducted by PCR followed by the
      appropriate restriction enzyme digestion [PCR-restriction fragment length
      polymorphism (PCR-RFLP)]. RESULTS: The most common BRCA1/BRCA2 mutations were
      identified in 30 patients with ovarian cancer. These mutations were not found in
      controls. The lowest p values of the trend test (p trend) were observed for the
      APC rs351771 and rs11954856 SNPs in patients with ovarian cancer (p trend = 0.006
      and p trend = 0.007, respectively). Using a dominant inheritance model, we found
      that the APC rs11954856 SNP is associated with an increased risk of ovarian
      cancer development [odds ratio = 2.034 (95 % CI 1.302-3.178); p = 0.002]. We also
      observed significant allelic differences for the APC rs351771 SNP between
      patients and controls (p = 0.006). CONCLUSION: Our study demonstrated
      significantly increased APC rs11954856 and rs351771 SNP frequencies in Polish
      women with ovarian cancer.

PMID- 24078349
TI  - Deformable image registration for temporal subtraction of chest  radiographs.
AB  - PURPOSE: Temporal subtraction images constructed from image registration can
      facilitate the visualization of pathologic changes. In this study, we propose a
      deformable image registration (DIR) framework for creating temporal subtraction
      images of chest radiographs. METHODS: We developed a DIR methodology using two
      different image similarity metrics, varying flow (VF) and compressible flow (CF).
      The proposed registration method consists of block matching, filtering, and
      interpolation. Specifically, corresponding point pairs between reference and
      target images are initially determined by minimizing a nonlinear least squares
      formulation using grid-searching optimization. A two-step filtering process,
      including least median of squares filtering and backward matching filtering, is
      then applied to the estimated point matches in order to remove erroneous matches.
      Finally, moving least squares is used to generate a full displacement field from
      the filtered point pairs. RESULTS: We applied the proposed DIR method to 10 pairs
      of clinical chest radiographs and compared it with the demons and B-spline
      algorithms using the five-point rating score method. The average quality scores
      were 2.7 and 3 for the demons and B-spline methods, but 3.5 and 4.1 for the VF
      and CF methods. In addition, subtraction images improved the visual perception of
      abnormalities in the lungs by using the proposed method. CONCLUSION: The VF and
      CF models achieved a higher accuracy than the demons and the B-spline methods.
      Furthermore, the proposed methodology demonstrated the ability to create
      clinically acceptable temporal subtraction chest radiographs that enhance
      interval changes and can be used to detect abnormalities such as non-small cell
      lung cancer.

PMID- 24078350
TI  - Incorporating novel agents in the management of elderly myeloma patients.
AB  - In recent years, the treatment of multiple myeloma has undergone significant
      changes. The availability of novel agents bortezomib, thalidomide and
      lenalidomide considerably improved the outcome of patients. The advantages
      related to the use of novel agents have been shown in various studies in patients
      eligible and ineligible for transplant. In elderly patients, novel agents have
      also revolutionized the treatment paradigm and have replaced the traditional
      melphalan-prednisone regimen. A sequential approach consisting of an induction
      regimen associated with a high rate of complete response, followed by
      consolidation/maintenance therapy, induces a profound cytoreduction and delays
      relapse, thus improving survival. Patients older than 75 years or who are
      otherwise vulnerable are more susceptible to adverse events. In this setting,
      less toxic regimens and appropriate dose-reductions should be adopted. This
      article provides an overview of the main trials for transplant-ineligible
      multiple myeloma patients. Recommendations on how to manage unfit patients and
      treatment-related toxicities are also provided.

PMID- 24078351
TI  - Thrombembolic complications after total ankle replacement.
AB  - The literature addressing functional outcome and survivorship of prosthesis
      components is constantly growing. However, the data on thromboprophylaxis and
      thrombembolic complications in patients who underwent TAR are scarce. A total of
      31 studies were included in the systemic literature review. The incidence of
      thrombembolic complications varied between 0.0 % and 9.8 %. Most commonly, low
      molecular weight heparin was used as thromboprophylaxis for 6 weeks
      postoperatively. The incidence of thrombembolic complications was comparable with
      that of symptomatic deep vein thrombosis in patients with total knee or hip
      replacement.

PMID- 24078352
TI  - Computational determination of the pigment binding motif  in the chlorosome
      protein a of green sulfur bacteria.
AB  - We present a molecular-scale model of Bacteriochlorophyll a (BChl a) binding to
      the chlorosome protein A (CsmA) of Chlorobaculum tepidum, and the aggregated
      pigment-protein dimer, as determined from protein-ligand docking and quantum
      chemistry calculations. Our calculations provide strong evidence that the BChl a
      molecule is coordinated to the His25 residue of CsmA, with the magnesium center
      of the bacteriochlorin ring situated?3 A degrees  from the imidazole nitrogen
      atom of the histidine sidechain, and the phytyl tail aligned along the nonpolar
      residues of the a-helix of CsmA. We also confirm that the Qy band in the
      absorption spectra of BChl a experiences a large (?16 to ?43 nm) redshift when
      aggregated with another BChl a molecule in the CsmA dimer, compared to the BChl a
      in solvent; this redshift has been previously established by experimental
      researchers. We propose that our model of the BChl a-CsmA binding motif, where
      the dimer contains parallel aligned N-terminal regions, serves as the smallest
      repeating unit in a larger model of the para-crystalline chlorosome baseplate
      protein.

PMID- 24078353
TI  - Influence and predictive capacity of climate anomalies on daily to decadal
      extremes in canopy photosynthesis.
AB  - Significant advances have been made over the past decades in capabilities to
      simulate diurnal and seasonal variation of leaf-level and canopy-scale
      photosynthesis in temperate and boreal forests. However, long-term prediction of
      future forest productivity in a changing climate may be more dependent on how
      climate and biological anomalies influence extremes in interannual to decadal
      variability of canopy ecosystem carbon exchanges. These exchanges can differ
      markedly from leaf level responses, especially owing to the prevalence of long
      lags in nutrient and water cycling. Until recently, multiple long-term (10+ year)
      high temporal frequency (daily) observations of canopy exchange were not
      available to reliably assess this claim. An analysis of one of the longest
      running North American eddy covariance flux towers reveals that single climate
      variables do not adequately explain carbon exchange anomalies beyond the seasonal
      timescale. Daily to weekly lagged anomalies of photosynthesis positively
      autocorrelate with daily photosynthesis. This effect suggests a negative feedback
      in photosynthetic response to climate extremes, such as anomalies in
      evapotranspiration and maximum temperature. Moisture stress in the prior season
      did inhibit photosynthesis, but mechanisms are difficult to assess. A complex
      interplay of integrated and lagged productivity and moisture-limiting factors
      indicate a critical role of seasonal thresholds that limit growing season length
      and peak productivity. These results lead toward a new conceptual framework for
      improving earth system models with long-term flux tower observations.

PMID- 24078355
TI  - Introduction: promoting concept driven teaching strategies in biochemistry and
      molecular biology.

PMID- 24078356
TI  - Raising environmental awareness through applied biochemistry laboratory
      experiments.
AB  - Our environment is under constant pressure and threat from various sources of
      pollution. Science students, in particular chemistry students, must not only be
      made aware of these issues, but also be taught that chemistry (and science) can
      provide solutions to such real-life issues. To this end, a newly developed
      biochemistry laboratory experiment is described that guides students to learn
      about the applicability of peroxidase enzymes to degrade organic dyes (as model
      pollutants) in simulated waste water. In addition to showing how enzymes can
      potentially be used for waste water remediation, various factors than can affect
      enzyme-based reactions such as pH, temperature, concentration of
      substrates/enzymes, and denaturants can also be tested. This "applied
      biotechnology" experiment was successfully implemented in an undergraduate
      biochemistry laboratory course to enhance students' learning of environmental
      issues as well important biochemistry concepts. Student survey confirmed that
      this laboratory experiment was successful in achieving the objectives of raising
      environmental awareness in students and illustrating the usefulness of chemistry
      in solving real-life problems. This experiment can be easily adopted in an
      introductory biochemistry laboratory course and taught as an inquiry-guided
      exercise.

PMID- 24078357
TI  - Commentary: teaching biochemistry and molecular biology in 3D: the new next
      generation science standards.

PMID- 24078358
TI  - Fatty acid metabolism: a metabolic verse.

PMID- 24078361
TI  - Reflections on using theory in research on continuing education in the health
      professions.

PMID- 24078360
TI  - A late recognition of tapia syndrome: a case report and literature review.
AB  - Tapia syndrome is characterized by concurrent paralysis of the recurrent
      laryngeal and hypoglossal nerves. The mechanism is associated with airway
      manipulation in 70% of patients and is attributed to compression or stretching of
      these nerves. Diagnosis is based on recognition of the concurrent paralyses and
      investigations to exclude central or vascular causes. Treatment is supportive,
      with emphasis on empiric corticosteroids and dysphagia therapy. Recovery is
      excellent in 30% of patients, incomplete in 39% of patients, and none in over 26%
      of patients. A case of a 48-year-old woman is described, who was diagnosed with
      Tapia syndrome 3 years after the suspected injury.

PMID- 24078362
TI  - The 2013 Journal of Continuing Education in the Health Professions Award for
      Excellence in Research.

PMID- 24078363
TI  - Effect of a performance improvement CME activity on management of patients with
      diabetes.
AB  - INTRODUCTION: Primary care in the United States faces unprecedented challenges
      from an aging population and the accompanying prevalence of chronic disease. In
      response, continuing medical education (CME) initiatives have begun to adopt the
      principles of performance improvement (PI) into their design, although currently
      there is a dearth of evidence from national initiatives supporting the
      effectiveness of this methodology. The specific aim of this study was to
      demonstrate the value of a national PI-CME activity to improve the performance of
      physicians treating patients with diabetes. METHODS: We analyzed data from the
      American Academy of Family Physicians' METRIC(r) PI-CME activity in a cohort of
      family physician learners. The study utilized the 3-stage design standard
      approved for PI-CME. Baseline and follow-up performance data across a range of
      clinical and systems-based measures were compared in aggregate. RESULTS: Data
      were assessed for 509 learners who completed the activity. Statistically
      significant changes occurred both for self-assessment of a range of practice
      aspects and for diabetes care measures. Learners recognized that the organization
      of their practices had improved, and mechanisms were in place for better staff
      feedback, as well as aspects of patient self-management. Based on the clinical
      data obtained from 11 538 patient charts, 6 out of 8 diabetes measures were
      significantly improved. DISCUSSION: The activity appears to have had a positive,
      measurable impact on the medical practice of learners and suggests that, when
      appropriately designed and executed, PI-CME on a national scale can be a useful
      vehicle to influence performance change in physicians and to inform future CME
      activities.

PMID- 24078364
TI  - Cultural competence education for practicing physicians: lessons in cultural
      humility, nonjudgmental behaviors, and health beliefs elicitation.
AB  - INTRODUCTION: Although numerous studies have examined cultural competence
      training, debate still exists about efficacious approaches to this training.
      Furthermore, little focus has been placed on training and evaluating practicing
      physicians. METHODS: A skills-based course on culturally competent diabetes care
      was developed and subsequently tested in a controlled trial of primary physicians
      caring for patients enrolled in one state's Medicaid program. We hypothesized
      that physicians completing the course would show higher levels of self-reported
      cultural competence as measured by a Cultural Competence Assessment Tool (CCAT)
      than those in the control group. Differences in CCAT subscale scores were also
      compared. RESULTS: Ninety physicians completed the study, with 41 in the control
      and 49 in the intervention group. Most were female (66%), with an average age of
      44, and 12 years in practice. There were no significant differences on total CCAT
      score (212.7 +/- 26.7 for control versus 217.2 +/- 28.6 for intervention, p =
      .444) or subscales measuring cultural knowledge. There were significant positive
      differences on the subscales measuring physicians' nonjudgmental
      attitudes/behaviors (subscale score 2.38 +/- 0.46 for control versus 2.69 +/-
      0.52 for intervention, p = .004) and future likelihood of eliciting patients'
      beliefs about diabetes and treatment preferences (3.11 +/- 0.53 for control
      versus 3.37 +/- 0.45 for intervention, p = .014). There was, however, a
      significant negative difference on the subscale measuring cultural self-awareness
      (3.48 +/- 0.36 for control versus 3.26 +/- 0.48 for intervention, p = .018).
      DISCUSSION: A predominantly skills-based approach to training physicians did not
      change aggregate measures of cultural competence, but did affect key attitudes
      and behaviors, which may better reflect the goals of cultural competence
      training.

PMID- 24078365
TI  - Evolution of a remedial CME course in professionalism: addressing learner needs,
      developing content, and evaluating outcomes.
AB  - INTRODUCTION: Scant information is available about the nature of the professional
      violations resulting in referral of physicians for remedial continuing medical
      education (CME). The CME program at Case Western Reserve University (CWRU) School
      of Medicine has developed the Intensive Course in Medical Ethics, Boundaries, and
      Professionalism (medical ethics course) for physician referrals due to ethical
      breaches. In this report, the authors present 7 years of data regarding the type
      of behavior that resulted in course referral as well as information regarding
      course and outcome evaluation development and participant demographics. METHODS:
      The medical ethics course has been designed in consultation with licensure
      agencies to address the learning needs of physicians with problems in the areas
      of boundary maintenance and ethics. Teaching methods and outcome evaluations
      include lectures, case discussions, multiple-choice question tests, skill
      practice sessions, and writing a reflective essay based on the participants'
      ethical lapse. Information is also gathered regarding participant demographics,
      training, and practice characteristics. RESULTS: Between September 2005 and
      February 2012, 358 learners participated in the course. The average age was 52
      years and 73% were board certified. Of the 269 physicians who wrote a reflective
      essay, the reasons for referral included prescribing of controlled drugs, sexual
      boundary issues, providing services to family or friends, not maintaining proper
      medical records, and billing issues. DISCUSSION: This report outlines the
      strategies used by CWRU to develop remedial CME courses using the medical ethics
      course as an example for course and outcome evaluation development. This is the
      first report characterizing the type and frequency of the medical ethics
      violations that result in mandatory participation in remedial CME.

PMID- 24078366
TI  - Geriatrics, interprofessional practice, and interorganizational collaboration: a
      knowledge-to-practice intervention for primary care teams.
AB  - INTRODUCTION: Caring for frail seniors requires health professionals with skills
      and knowledge in 3 core competencies: geriatrics, interprofessional practice, and
      interorganizational collaboration. Despite a growing population of frail seniors
      in all developed countries, significant gaps exist in preparation of health
      professionals in these skills. To help close these gaps, a knowledge-to-practice
      (KTP) process was undertaken to increase the capacity of newly created family
      health teams and longer standing Community Health Centers in the Province of
      Ontario, Canada. METHODS: Each team identified a staff member to become its
      facilitator in the 3 core skill sets. Guided by a KTP framework, a set of
      training modules were created, compiled into a digital toolkit for transfer into
      practice, translated in a multimethods workshop, and implemented using a variety
      of strategies to optimize practice change. RESULTS: Staff from 82% of the
      targeted primary care teams learned to use the toolkit in a train-the-facilitator
      process that was highly valued, and prompted a range of changes in personal and
      team practice. A digital toolkit for primary care teams remains an enduring and
      often used resource. DISCUSSION: Closing the knowledge gap in the core
      competencies for frailty focused care is complex. A KTP framework helped guide a
      staged multimethod process that produced both individual and team practice change
      and on online toolkit that has a continuing influence.

PMID- 24078367
TI  - Sailing a safe ship: improving patient safety by enhancing the leadership skills
      of new consultant specialist surgeons.
AB  - INTRODUCTION: The potential for "discontinuities in care" arising from the
      turbulent transition from specialist trainee to consultant specialist presents
      risks to patient safety. But it is easy to lose sight of the affective needs of
      individuals facing the burden of keeping patients safe. This article describes a
      2-day program focused on new and prospective consultant specialist ophthalmic
      surgeons entitled "Sailing a Safe Ship" (SASS). The purpose was to facilitate
      understanding and analysis of their personal holistic learning needs and enhance
      individual agency in optimizing learning during the transition period. METHODS:
      The program used gaming, team challenges, meta-planning, role play and
      professional actors, interactive presentations, and self-analysis tools to
      portray the real world of consultant specialist practice in terms of ill-defined
      problems requiring "elite communication" and effective negotiation of value
      differences and priorities for their resolution. Participants' insights into
      their individual learning were recorded in scheduled reflective sessions. The
      immediate impact on their learning was also considered in terms of direct
      (instructional) and indirect (nurturant) effects. RESULTS: Participants' insights
      reflected 4 key themes: admitting vulnerability and uncertainty, taking
      responsibility for managing risk, being self-aware and reflexive, and
      internalizing authentic leadership. Four instructional and 4 nurturant effects
      were revealed. Preliminary findings on long-term impact on participants' practice
      are outlined. DISCUSSION: Evidence from the evaluation indicated that
      participants felt empowered to construct a personal strategic response to
      unfamiliar and unanticipated workplace demands and pressures, adopt a capability
      mindset that would accelerate their capacity to fulfill an enhanced leadership
      role, and take a holistic approach to their continuing self-directed development
      as leaders and educators.

PMID- 24078368
TI  - A single exposure to acrolein desensitizes baroreflex responsiveness and
      increases cardiac arrhythmias in normotensive and hypertensive rats.
AB  - Short-term exposure to air pollutants has been linked to acute cardiovascular
      morbidity and mortality. Even in the absence of overt signs or symptoms,
      pollutants can cause subtle disruptions to internal compensatory mechanisms,
      which maintain homeostatic balance in response to various environmental and
      physiological stressors. We hypothesized that a single exposure to acrolein, a
      ubiquitous gaseous air pollutant, would decrease the sensitivity of baroreflex
      (BRS), which maintains blood pressure by altering heart rate (HR), modify cardiac
      electrophysiological properties and increase arrhythmia in rats. Wistar-Kyoto
      normotensive (WKY) and spontaneously hypertensive (SH) rats implanted with
      radiotelemeters and a chronic jugular vein catheter were tested for BRS using
      phenylephrine and sodium nitroprusside 2 days before and 1 h after whole-body
      exposure to 3 ppm acrolein (3 h). HR and electrocardiogram (ECG) were
      continuously monitored for the detection of arrhythmia in the pre-exposure,
      exposure and post-exposure periods. Whole-body plethysmography was used to
      continuously monitor ventilation in conscious animals. SH rats had higher blood
      pressure, lower BRS and increased frequency of AV block as evidence by non
      conducted p-waves when compared with WKY rats. A single exposure to acrolein
      caused a decrease in BRS and increased incidence of arrhythmia in both WKY and SH
      rats. There were minimal ECG differences between the strains, whereas only SH
      rats experienced irregular breathing during acrolein. These results demonstrate
      that acrolein causes immediate cardiovascular reflexive dysfunction and
      persistent arrhythmia in both normal and hypertensive animals. As such,
      homeostatic imbalance may be one mechanism by which air pollution increases risk
      24 h after exposure, particularly in people with underlying cardiovascular
      disease. 

PMID- 24078369
TI  - The impact of dental treatment on the salivary cortisol levels of children with
      severe early childhood caries.
AB  - AIM: To compare salivary cortisol levels of caries-free children with those of
      children with severe early childhood caries (S-ECC) before and 3 months after
      comprehensive dental treatment. METHODS: Thirty children with S-ECC were matched
      with 30 caries-free children from middle income families with college-educated
      working mothers. Early-morning saliva samples were collected from the children
      using the passive drool method. Post-treatment saliva samples were collected 3
      months after completion of treatment in the S-ECC group. Salivary cortisol levels
      were analysed using electrochemiluminescence immunoassay. RESULTS: Salivary
      cortisol levels of caries-free children were significantly lower than both the
      pre-treatment and post-treatment levels of children with S-ECC (F = 26.221, p <
      0.0001). The pre-treatment cortisol levels of children with S-ECC were
      significantly higher than the post-treatment levels (t = 2.588, p = 0.015). No
      significant differences in cortisol levels were observed between genders or
      between children treated over multiple visits under local analgesia and in a
      single visit under general anaesthesia. CONCLUSION: Dental treatment
      significantly reduced the salivary cortisol levels of children with S-ECC,
      however, the post-treatment levels remained significantly higher than those of
      caries-free children.

PMID- 24078371
TI  - Automated implant segmentation in cone-beam CT using edge  detection and particle
      counting.
AB  - PURPOSE: To develop a fully automated, accurate and robust segmentation technique
      for dental implants on cone-beam CT (CBCT) images. METHODS: A head-size
      cylindrical polymethyl methacrylate phantom was used, containing titanium rods of
      5.15 mm diameter. The phantom was scanned on 17 CBCT devices, using a total of 39
      exposure protocols. Images were manually thresholded to verify the applicability
      of adaptive thresholding and to determine a minimum threshold value (Tmin). A
      three-step automatic segmentation technique was developed. Firstly, images were
      pre-thresholded using Tmin. Next, edge enhancement was performed by filtering the
      image with a Sobel operator. The filtered image was thresholded using an
      iteratively determined fixed threshold (Tedge) and converted to binary. Finally,
      a particle counting method was used to delineate the rods. The segmented area of
      the titanium rods was compared to the actual area, which was corrected for
      phantom tilting. RESULTS: Manual thresholding resulted in large variation in
      threshold values between CBCTs. After applying the edgeenhancing filter, a stable
      Tedge value of 7.5% was found. Particle counting successfully detected the rods
      for all but one device. Deviations between the segmented and real area ranged
      between -2.7 and +14.4mm(2) with an average absolute error of 2.8mm(2).
      Considering the diameter of the segmented area, submillimeter accuracy was seen
      for all but two data sets. CONCLUSION: A segmentation technique was defined which
      can be applied to CBCT data for an accurate and fully automatic delineation of
      titanium rods. The technique was validated in vitro and will be further tested
      and refined on patient data.

PMID- 24078370
TI  - Alcohol use and sexual risk behaviors among individuals infected with HIV: a
      systematic review and meta-analysis 2012 to early 2013.
AB  - The purpose of this meta-analytic study is to summarize the current science
      concerning the (a) prevalence of alcohol use, (b) prevalence of sexual risk
      behaviors, and (c) association between alcohol use and sexual risk behaviors
      among people livingwithHIV/AIDS (PLWHA). Studies were included if they sampled
      PLWHA, evaluated both alcohol use and sexual risk behavior (e.g., condom use,
      multiple partners), and were published between January 1, 2012, and April 1,
      2013. Comprehensive electronic database searches located 728 published studies
      with relevant keywords; 17 studies (k =19 reports) were included. Findings
      indicate that a substantial proportion of PLWHA use alcohol and engage in sexual
      risk behaviors. Among PLWHA, alcohol use was significantly associated with
      unprotected sex (d +=0.23, 95 % CI=0.05, 0.40; k =5). Secondary prevention
      programs for PLWHA that address alcohol use in the context of sexual behavior are
      needed.

PMID- 24078372
TI  - The superiority of allogeneic hematopoietic stem cell transplantation from
      unrelated donor over chemotherapy for adult patients with high-risk acute
      lymphoblastic leukemia in first remission.
AB  - For adult patients with acute lymphoblastic leukemia (ALL), allogeneic
      hematopoietic stem cell transplantation(allo-HSCT) from HLA-matched related
      donors(MSD) is recommended for standard and high-risk patients. The role of
      unrelated donor transplantation (URD) in first remission has not been fully
      determined. We sought to compare directly the outcome of URD allo-HSCT and
      chemotherapy in patients with high-risk ALL. In this single center retrospective
      analysis, we included 74 consecutive adult patients with high-risk ALL in first
      complete remission(CR) and without a sibling donor, in which 32 patients received
      URD allo-HSCT in CR1 with busulfan-cyclophosphamide preparation regimen and in
      vivo T-cell depletion with anti-T-lymphoglobulin (ATG). The remaining 42 patients
      received chemotherapy consolidation and maintenance only in first remission. With
      median follow-up of 18 months, in the URD allo-HSCT group, the relapse rate(RR)
      was 30.6 +/- 11.4 % which was significantly lower than that of the chemotherapy
      group (80.5 +/- 10.1 %,p < 0.001), while non-relapse mortality (NRM) was
      higher(16.4 +/- 6.7 % vs. 0, p = 0.028). Overall, 3-year leukemia free survival
      (LFS) was superior in the URD allo-HSCT group compared to chemotherapy group
      (57.8 +/- 10.6 vs.19.5 +/- 10.5 %, p = 0.002), as was 3-year overall survival(OS,
      63.5 +/- 13.3 vs. 31.6 +/- 10.6 %, p = 0.016). URDHSCT was the only factor
      associated with improved OS, LFS and reduced RR in multivariate analysis. Based
      on our data, URD allo-HSCT significantly reduced the relapse in high-risk ALL and
      the benefit translated into improvement in both LFS and OS. Prospective studies
      based on availability of HLA-matched URD are warranted to evaluate the precise
      role of URD transplantation in adult ALL.

PMID- 24078373
TI  - Evaluation of a Swedish version of the Strengthening Families Programme.
AB  - BACKGROUND: Adolescents' alcohol consumption is a public health concern in Sweden
      as well as in many other countries. Underage drinking is associated with
      increased risks of alcohol-related injuries, risky sexual behaviours and
      dependence later in life. Different strategies have been used in the effort to
      prevent this behaviour, and to postpone the onset of alcohol. The Strengthening
      Families Programme 10-14 (SFP 10-14) from the USA has been highlighted as one of
      the more effective prevention programmes. The aim of the present article was to
      evaluate the effectiveness of a culturally adapted Swedish version of the SFP 10
      14. METHODS: This was a cluster randomized controlled trial including 587 sixth
      grade students (age 12) and their parents in 19 elementary schools in Stockholm.
      Schools were randomly assigned to either control (9 schools, 216 students) or to
      the family skills training intervention (10 schools, 371 students). The SFP
      Swedish version consisted of two parts with seven and five sessions,
      respectively, held separately for youths and parents except two joint family
      sessions. Measures of students' self-reported episodes of drunkenness, smoking,
      illicit drug use and other norm-breaking behaviours were collected at baseline
      (March 2003) and at three subsequent yearly surveys. Data were analysed using
      multilevel models with an intention-to-treat approach. RESULTS: No preventive
      effects were found for smoking, alcohol and illicit drug use and other norm
      breaking behaviours, nor did moderators affect the outcome. CONCLUSION: The
      Swedish version of the SFP 10-14 was not effective in preventing youths'
      substance use in a Swedish context.

PMID- 24078374
TI  - Levels of advertised unprotected vaginal and oral sex by independent indoor
      female sex workers in West Yorkshire, UK.
AB  - OBJECTIVES: To assess the proportion of independent indoor female sex workers
      (FSW) in West Yorkshire, UK who advertise unprotected sex, and to investigate any
      association with cost, location and provision of anal sex. METHODS: Data on
      whether independent indoor FSW (defined as those not advertising via an escort
      agency or through a parlour) advertised unprotected sexual services, along with
      demographic data, were collected from 462 advertisement profiles of FSW in West
      Yorkshire from the website http://www.adultwork.com. Independent t test and
      chi(2) statistics were used to test the association between advertised
      unprotected vaginal and oral sex, and FSW age, cost of services, location and
      whether they advertised anal sex. RESULTS: Unprotected vaginal sex was advertised
      by 8% of FSW, and unprotected oral sex by 74% of FSW. FSW advertising unprotected
      vaginal sex were more likely to live in Wakefield and Bradford than in Leeds, had
      significantly lower hourly rates, and were more likely to advertise anal sex.
      CONCLUSIONS: Advertised condom use for vaginal and oral sex by independent indoor
      FSW in West Yorkshire was significantly lower than reported rates of protected
      sex found in previous studies based in London and the south of England. The
      advertisement of unprotected vaginal sex is associated with factors such as lower
      hourly rates and the advertisement of higher risk anal sex, which may signify
      greater economic need. FSW offering unprotected sex therefore represent an at
      risk target group for health promotion.

PMID- 24078381
TI  - Carbon black nanoparticle intratracheal instillation does not alter cardiac gene
      expression.
AB  - Exposure to nanoparticles has been associated with inflammation-related
      progression of atherosclerosis. To examine nanoparticle-induced cardiac effects
      in more detail, we characterized heart gene expression profiles alongside plasma
      proteins associated with cardiovascular disease in C57BL/6 mice intratracheally
      instilled with vehicle or 0.162 mg Printex 90 carbon black nanoparticles (CBNPs).
      Mice were killed 1, 3, and 28 days after the exposure and expression profiles
      were derived using DNA microarrays. Cardiac gene expression was unperturbed by
      CBNP exposure in two independent experiments, despite substantive changes in
      pulmonary and hepatic gene expression. MicroRNAs were not affected. Plasma levels
      of cell adhesion molecules (sE-selectin, sICAM-1, sVCAM-1) and total PAI-1 were
      immediately increased up to day 3, whereas Apo-A1 and Apo-E were marginally
      decreased on day 1. These data suggest that though adverse cardiovascular effects
      are likely following CBNP exposure, these effects are unlikely to be mediated by
      major direct effects on cardiac gene expression.

PMID- 24078383
TI  - Sublethal heat shock induces premature senescence rather than apoptosis in human
      mesenchymal stem cells.
AB  - Stem cells in adult organism are responsible for cell turnover and tissue
      regeneration. The study of stem cell stress response contributes to our knowledge
      on the mechanisms of damaged tissue repair. Previously, we demonstrated that
      sublethal heat shock (HS) induced apoptosis in human embryonic stem cells. This
      study aimed to investigate HS response of human adult stem cells. Human
      mesenchymal stem cells (MSCs) cultivated in vitro were challenged with sublethal
      HS. It was found that sublethal HS did not affect the cell viability assessed by
      annexin V/propidium staining. However, MSCs subjected to severe HS exhibited
      features of stress-induced premature senescence (SIPS): irreversible cell cycle
      arrest, altered morphology, increased expression of senescence-associated beta
      galactosidase (SA-beta-gal) activity, and induction of cyclin-dependent kinase
      inhibitor p21 protein. High level of Hsp70 accumulation induced by sublethal HS
      did not return to the basal level, at least, after 72 h of the cell recovery when
      most cells exhibited SIPS hallmarks. MSCs survived sublethal HS, and resumed
      proliferation sustained the properties of parental MSCs: diploid karyotype,
      replicative senescence, expression of the cell surface markers, and capacity for
      multilineage differentiation. Our results showed for the first time that in human
      MSCs, sublethal HS induced premature senescence rather than apoptosis or
      necrosis. MSC progeny that survived sublethal HS manifested stem cell properties
      of the parental cells: limited replicative life span and multilineage capacity.

PMID- 24078382
TI  - The corneal epithelial basement membrane: structure, function, and disease.
AB  - The corneal epithelial basement membrane (BM) is positioned between basal
      epithelial cells and the stroma. This highly specialized extracellular matrix
      functions not only to anchor epithelial cells to the stroma and provide
      scaffolding during embryonic development but also during migration,
      differentiation, and maintenance of the differentiated epithelial phenotype.
      Basement membranes are composed of a diverse assemblage of extracellular
      molecules, some of which are likely specific to the tissue where they function;
      but in general they are composed of four primary components--collagens, laminins,
      heparan sulfate proteoglycans, and nidogens--in addition to other components such
      as thrombospondin-1, matrilin-2, and matrilin-4 and even fibronectin in some BM.
      Many studies have focused on characterizing BM due to their potential roles in
      normal tissue function and disease, and these structures have been well
      characterized in many tissues. Comparatively few studies, however, have focused
      on the function of the epithelial BM in corneal physiology. Since the normal
      corneal stroma is avascular and has relatively low keratocyte density, it is
      expected that the corneal BM would be different from the BM in other tissues. One
      function that appears critical in homeostasis and wound healing is the barrier
      function to penetration of cytokines from the epithelium to stroma (such as
      transforming growth factor beta-1), and possibly from stroma to epithelium (such
      as keratinocyte growth factor). The corneal epithelial BM is also involved in
      many inherited and acquired corneal diseases. This review examines this structure
      in detail and discusses the importance of corneal epithelial BM in homeostasis,
      wound healing, and disease.

PMID- 24078384
TI  - Identification of signaling pathways modulated by RHBDD2 in breast cancer cells:
      a link to the unfolded protein response.
AB  - Rhomboid domain containing 2 (RHBDD2) was previously observed overexpressed and
      amplified in breast cancer samples. In order to identify biological pathways
      modulated by RHBDD2, gene expression profiles of RHBDD2 silenced breast cancer
      cells were analyzed using whole genome human microarray. Among the statistically
      significant overrepresented biological processes, we found protein metabolism
      with the associated ontological terms folding , ubiquitination, and proteosomal
      degradation-cell death, cell cycle, and oxidative phosphorylation. In addition,
      we performed an in silico analysis searching for RHBDD2 co-expressed genes in
      several human tissues. Interestingly, the functional analysis of these genes
      showed similar results to those obtained with the microarray data, with negative
      regulation of protein metabolism and oxidative phosphorylation as the most
      enriched gene ontology terms. These data led us to hypothesize that RHBDD2 might
      be involved in endoplasmic reticulum (ER) stress response. Thus, we specifically
      analyzed the unfolding protein response (UPR) of the ER stress process. We used a
      lentivirus-based approach for stable silencing of RHBDD2 mRNA in the T47D breast
      cancer cell line, and we examined the transcriptional consequences on UPR genes
      as well as the phenotypic effects on migration and proliferation processes. By
      employing dithiothreitol as an UPR inducer, we observed that cells with silenced
      RHBDD2 showed increased expression of ATF6, IRE1, PERK, CRT, BiP, ATF4, and CHOP
      (p <0.01). We also observed that RHBDD2 silencing inhibited colony formation and
      decreased cell migration. Based on these studies, we hypothesize that RHBDD2
      overexpression in breast cancer could represent an adaptive phenotype to the
      stressful tumor microenvironment by modulating the ER stress response.

PMID- 24078385
TI  - Genetics and the molecular pathogenesis of pulmonary arterial hypertension.
AB  - Mutations in the bone morphogenetic protein type II receptor (BMPR-II) gene
      (BMPR2) have been recognized to cause heritable PAH (HPAH). Recent studies
      focused on novel BMPR2 mutations in the Asian population and provided evidence
      for genotype-phenotype correlations. A candidate gene strategy has suggested
      additional mutations in SMAD, TBX4 and TSP1 in PAH. A genome-wide association
      study (GWAS) identified an association at the CBLN2 locus with PAH. Studies have
      addressed the role of additional factors required for disease penetrance. The
      unbalance between TGF beta1 and BMPRII signaling may stimulate inflammatory
      cytokine expression and leukocyte extravasation. Epigenetics, including DNA
      methylation and microRNAs, appear to play a role in the development of PAH. Next
      generation sequencing with advances in bioinformatics will provide further
      insights into the underlying genetic and epigenetic architecture underlying the
      pathobiology of PAH.

PMID- 24078386
TI  - The enigmatic ERH protein: its role in cell cycle, RNA splicing and cancer.
AB  - Enhancer of rudimentary homolog (ERH) is a small, highly conserved protein among
      eukaryotes. Since its discovery nearly 20 years ago, its molecular function has
      remained enigmatic. It has been implicated to play a role in transcriptional
      regulation and in cell cycle. We recently showed that ERH binds to the Sm complex
      and is required for the mRNA splicing of the mitotic motor protein CENP-E.
      Furthermore, cancer cells driven by mutations in the KRAS oncogene are
      particularly sensitive to RNAi-mediated suppression of ERH function, and ERH
      expression is inversely correlated with survival in colorectal cancer patients
      whose tumors harbor KRAS mutation. These recent findings indicate that ERH plays
      an important role in cell cycle through its mRNA splicing activity and is
      critically required for genomic stability and cancer cell survival.

PMID- 24078388
TI  - Anatomophysiology of the pharyngo-upper esophageal area in light of high
      resolution manometry.
AB  - INTRODUCTION: The motility of the pharynx, upper esophageal sphincter (UES), and
      proximal esophagus is still poorly understood. These structures have anatomical
      and functional peculiarities that hinder the accurate study of their motility
      with the technology traditionally available. High-resolution manometry (HRM) has
      characteristics that make it more suitable for the study of the upper digestive
      tract. This study aims to evaluate in healthy volunteers, using HRM and
      transnasal pharyngoscopy, (1) the correlation between anatomical landmarks and
      HRM plots and (2) the normal values for manometric parameters of the pharynx,
      UES, and proximal esophagus. METHODS: We studied 40 asymptomatic volunteers with
      HRM (50 % male; median age, 27 years). Fourteen of those also underwent
      transnasal pharyngoscopy. RESULTS AND DISCUSSION: Pharyngeal peak pressure, rise
      time, recovery time, and duration of contraction were 128 mmHg (range, 100-164
      mmHg), 197 ms (range, 169-268 ms), 385 ms (range, 285-465 ms), and 604 ms (range,
      544-626 ms) at the velum and 116 mmHg (range, 97-139 mmHg), 128 ms (range, 100
      156 ms), 194 ms (range, 148-219 ms), and 336 ms (range, 267-386 ms) at the
      epiglottis, respectively. UES extension, basal pressure, residual pressure, and
      duration of relaxation were 3 cm (range, 2.6-3.6 cm), 76 mmHg (range, 58-109
      mmHg), 4.4 mmHg (range, 1.2-6.9 mmHg), and 678 ms (range, 636-757 ms),
      respectively. In the proximal esophagus, wave amplitudes at 2, 4, and 6 cm below
      the UES were 72 mmHg (range, 53-97 mmHg), 56 mmHg (range, 42-76 mmHg), and 48
      mmHg (range, 35-59 mmHg), respectively. CONCLUSIONS: In conclusion, normal values
      were established. These values may prove clinically useful and could contribute
      to future studies with dysphagic patients.

PMID- 24078387
TI  - Toward pluripotency by reprogramming: mechanisms and application.
AB  - The somatic epigenome can be reprogrammed to a pluripotent state by a combination
      of transcription factors. Altering cell fate involves transcription factors
      cooperation, epigenetic reconfiguration, such as DNA methylation and histone
      modification, posttranscriptional regulation by microRNAs, and so on.
      Nevertheless, such reprogramming is inefficient. Evidence suggests that during
      the early stage of reprogramming, the process is stochastic, but by the late
      stage, it is deterministic. In addition to conventional reprogramming methods,
      dozens of small molecules have been identified that can functionally replace
      reprogramming factors and significantly improve induced pluripotent stem cell
      (iPSC) reprogramming. Indeed, iPS cells have been created recently using chemical
      compounds only. iPSCs are thought to display subtle genetic and epigenetic
      variability; this variability is not random, but occurs at hotspots across the
      genome. Here we discuss the progress and current perspectives in the field.
      Research into the reprogramming process today will pave the way for great
      advances in regenerative medicine in the future.

PMID- 24078389
TI  - Somatic involvement assessed through a cumulative score  of clinical severity in
      patients with eating disorders.
AB  - PURPOSE: To evaluate the overall somatic involvement in patients with eating
      disorders (EDs). METHODS: The medical records of 206 patients (age 15-56 years,
      96.1% females) with diagnosis of anorexia nervosa (AN, n = 63, 30.6%), bulimia
      nervosa (BN, n = 78, 37.9%), or eating disorder not otherwise specified (EDNOS, n
      = 65, 31.6 %) were analyzed. A cumulative score of clinical severity (SCS) was
      computed according to the presence of physical, instrumental, and laboratory
      abnormalities, as well as to their prognostic impact. Based on the tertile
      distribution of SCS, three levels of severity were defined: low, medium, and
      high. RESULTS: A medium/high level of severity was found in 63% of the whole
      sample, 89% of AN, 49% of BN, and 55% of EDNOS. In the whole sample, the risk of
      medium/high SCS was significantly and inversely related to the body mass index
      (BMI) and to the lifetime minimum BMI. The severity level was significantly and
      positively associated with diagnosis of AN, duration of amenorrhea C1 year, and
      presence of ED-related symptoms. EDNOS patients showed a higher risk for
      increased SCS than BN patients, although not significantly. CONCLUSION: The non
      negligible frequency of a relevant somatic involvement in patients with EDNOS
      suggests that a transdiagnostic scoring system might be helpful to identify ED
      cases at risk of medical complications.

PMID- 24078390
TI  - Nitric oxide, S-nitrosation, and endothelial permeability.
AB  - S-Nitrosation is rapidly emerging as a regulatory mechanism in vascular biology,
      with particular importance in the onset of hyperpermeability induced by pro
      inflammatory agents. This review focuses on the role of endothelial nitric oxide
      synthase (eNOS)-derived nitric oxide (NO) in regulating S-Nitrosation of adherens
      junction proteins. We discuss evidence for translocation of eNOS, via caveolae,
      to the cytosol and analyze the significance of eNOS location for S-Nitrosation
      and onset of endothelial hyperpermeability to macromolecules.

PMID- 24078391
TI  - Functional role of transient conformations: Rediscovering "chronosteric effects"
      thirty years later.
AB  - Proteins are dynamic entities that exert, in some cases, their functions via
      complex pathways, involving active transient species. This phenomenon was
      highlighted for the first time in 1983 by Antonini et al. (J. Biol. Chem. 258,
      4676-4678), who demonstrated that at least one intermediate occurring in the
      formation of the bovine beta-trypsin-Kunitz inhibitor complex displayed catalytic
      properties different from those of the active enzyme and of the inactive enzyme
      inhibitor adduct. Since it was impossible to explain this phenomenon in terms of
      static three-dimensional structures, the term "chronosteric effects" was coined
      to capture the observation that transient species are relevant to protein
      function(s). Here, some recent results on the folding and function of proteins
      are reported on the light of chronosteric effects.

PMID- 24078392
TI  - Impact of exercise on muscle and nonmuscle organs.
AB  - Exercise is known to prevent and treat metabolic diseases such as diabetes.
      However, the underlying mechanisms are not fully understood, and there is
      currently much focus on detailing such pathways. Traditionally, much emphasis has
      been placed on skeletal muscle; however, recently, nonmuscle organs such as
      adipose tissue have been highlighted in mediating protective actions after
      training. Moreover, novel paracrine- and endocrine-signaling molecules have been
      shown to trigger important responses in nonmuscle organs after exercise. This is
      exciting because, when administered exogenously, such signals have obvious
      therapeutic potential. In this review, the authors have described some general
      and historical aspects of training and disease protection. The authors have also
      highlighted some of the current knowledge on how exercise impacts nonmuscle
      organs.

PMID- 24078393
TI  - Biochemical and structural aspects of the ATP-binding domain in inflammasome
      forming human NLRP proteins.
AB  - Nucleotide-binding domain and leucine-rich repeat-containing receptors (NLRs)
      regulate innate immunity by activating inflammatory responses in a variety of
      biological systems following the recognition of pathogen- or disease-associated
      molecular patterns. NLRs are characterized by a central nucleotide-binding and
      oligomerization (NACHT) domain found in P-loop NTPases. In this review, we detail
      the functional and structural properties of the NACHT domain of a subfamily of
      NLRs, the NLRPs (NLR containing a pyrin domain), based on previous studies,
      sequence analysis, homology modeling, and structure predictions. Several NLRPs
      have been found to regulate inflammatory responses through the assembly of
      oligomeric caspase 1-activating platforms known as inflammasomes, the 3
      dimensional structure of the NLRP NACHT domain has still not been solved.
      Homology modeling suggests that sequence variability within the NACHT domains of
      different NLRP family members may alter the topology of the ATP-binding pocket.
      Based on this finding, we discuss the potential therapeutic prospects aligned
      with the NACHT domain and the development of selective inhibitors of inflammasome
      activity.

PMID- 24078394
TI  - Iron homeostasis in insects: Insights from Drosophila studies.
AB  - Iron is essential for the survival of almost all organisms. Our current
      understanding of iron metabolism in different organisms suggests it is a
      partially conserved but not identical process. Many aspects of iron metabolism in
      insects remain poorly understood. This review summarizes what we know so far
      about insect iron homeostasis, including dietary iron absorption, iron transport
      and storage, as well as homeostasis regulation. New findings made in the model
      organism Drosophila are emphasized and their implications discussed.

PMID- 24078401
TI  - Molecular insight in gastric cancer induction: an overview of cancer stemness
      genes.
AB  - Gastric cancer is one of the most outgoing human cancers in the world. Two main
      functional types were described: Intestinal adenocarcinoma and diffuse one. The
      most important purpose of this review is to analyze and investigate the main
      genetic factors involved in tumorogenesis of stomach and the molecular mechanism
      of their expression regulation alongside with the importance of cancer stem cells
      and their relationship with gastric cancer. It is evident that proper diagnosis
      of molecular case of cancer may lead to absolute treatment and at least reduction
      in the disease severity. However, stemness factors such as Sox2, Oct3/4, and
      Nanog were related with induced pluripotent stem cells, proposing a correlation
      between these stemness factors and cancer stem cells. Moreover, aberrant
      induction by Helicobacter pylori of the intestinal-specific homeobox
      transcription factors, CDX1 and CDX2, also plays an important role in this
      modification. There are some genes which are directly activated by CDX1 in
      gastric cancer and distinguished stemness-related reprogramming factors like
      SALL4 and KLF5. Correspondingly, we also aimed to present the main important
      epigenetic changes such as DNA methylation, histone modification, and chromatin
      modeling of stemness genes in disease development. Remarkably, a better
      understanding of molecular bases of cancer may lead to novel diagnostic,
      therapeutic, and preventive approaches by some genetic and epigenetic changes
      such as gene amplifications, gene silencing by DNA methylation, losses of
      imprinting, LOH, and mutations. Consequently, genome-wide searches of gene
      expression are widely important for surveying the proper mechanisms of cancer
      emergence and development. Conspicuously, this review explains an outline of the
      molecular mechanism and new approaches in gastric cancer. 

PMID- 24078402
TI  - The novel heterocyclic trioxirane [(1,3,5-tris oxiran-2-yl)methyl)-1,3,5
      triazinane-2,4,6-trione (TATT)] exhibits a better anticancer effect than platinum
      based chemotherapy by induction of apoptosis and curcumin further enhances its
      chemosensitivity.
AB  - The heterocyclic trioxirane compound [1,3,5-tris((oxiran-2-yl)methyl)-1,3,5
      triazinane-2,4,6-trione (TATT)] is a synthetic compound which has been used as an
      experimental anticancer agent in human clinical trials. Curcumin, an active
      natural compound in turmeric and curry, is an ingredient commonly used in the
      traditional diet of many Asian countries. In the present study, we observed that
      TATT exhibited a better anticancer effect on chemoresistant human colorectal
      cancer HT-29 cells and displayed less cytotoxicity on normal human umbilical vein
      endothelial cells, compared with FDA-approved anticancer drugs (cisplatin,
      carboplatin, or oxaliplatin) using MTT assay. TATT also induced a stronger
      apoptotic effect than that seen with the three studied anticancer drugs, as
      characterized by externalization of phosphatidylserine using flow cytometry.
      Administration of caspase 8-specific inhibitor (z-IETD-fmk) and mitochondrial
      permeability transition pore inhibitor (cyclosporin A) demonstrated that TATT
      induced apoptosis proceeded via both extrinsic and intrinsic signaling pathways.
      It is noteworthy that coadministration of curcumin further significantly
      increased TATT-induced cytotoxicity, externalization of phosphatidylserine
      (representing early apoptosis), and the percentages of cells at the sub-G1 phase
      (representing late apoptosis), producing an additivity and/or synergistic effect,
      and vice versa. Suppression of nuclear NF-kappaB was involved in curcumin
      enhanced chemosensitivity of TATT. Overall, our data indicate that TATT exerts a
      chemotherapeutic effect on colorectal cancer cells and coadministration of
      curcumin enhances the treatment effect of TATT. 

PMID- 24078405
TI  - Positive Deviance: A New Tool for Infection Prevention and Patient Safety.
AB  - Positive deviance (PD) may have an important role in infection prevention and
      patient safety in the hospital. There are many descriptions of successful stories
      of PD in different sectors from public health to education to business. PD has
      been applied in the healthcare setting to improve hand hygiene compliance, reduce
      methicillin-resistant Staphylococcus aureus, and reduce bloodstream infections in
      an outpatient hemodialysis center. PD promotes dialogue among leaders, managers
      and healthcare workers, which is a key factor in establishing a safety culture.
      It also enables cultural changes aimed at empowering frontline workers (the
      positive deviants) to innovate and improve compliance with infection prevention
      measures. The structure and the process of PD, and its ability to offer a space
      for experience discussions, changing ideas and making plans that emerge from team
      participation will also be discussed.

PMID- 24078404
TI  - Species and inter-individual differences in metabolic capacity of di(2
      ethylhexyl)phthalate (DEHP) between human and mouse livers.
AB  - OBJECTIVES: This study was conducted to assess inter-species and inter-individual
      differences in the metabolism of di(2-ethylhexyl)phthalate (DEHP) in humans and
      mice. METHODS: The activities of four DEHP-metabolizing enzymes [lipase, UDP
      glucuronocyltransferase (UGT), alcohol dehydrogenase (ADH), aldehyde
      dehydrogenase (ALDH)] were measured in the livers of 38 human subjects of various
      ages and in eight 129/Sv male mice. RESULTS: Microsomal lipase activity was
      significantly lower in humans than in mice. The V max/K m value in humans was one
      seventh of that in mice, microsomal UGT activity in humans was a sixth of that in
      mice, and cytosolic ALDH activity for 2-ethylhexanal in humans was one-half of
      that in mice. In contrast, ADH activity for 2-ethylhexanol was twofold higher in
      humans than in mice. The total amount of DEHP urinary metabolites and the
      concentration of mono(2-ethylhexyl)phthalate (MEHP) were much higher in intact
      mice than in the U.S. general population based on data reported elsewhere,
      regardless of the similar estimated DEHP intake between these mice and the human
      reference population. However, mono(2-ethyl-5-oxo-hexyl)phthalate (5oxo-MEHP) and
      mono(2-ethyl-5-carboxypentyl)phthalate (5cx-MEPP) levels were higher in the
      latter than in the former. Of note, inter-subject variability in the activities
      of all enzymes measured was 10-26-fold. CONCLUSION: The inter-individual
      variation in the metabolism of DEHP in humans may be greater than the difference
      between mice and humans (inter-species variation), and both may affects the risk
      assessment of DEHP.

PMID- 24078406
TI  - The impact of financial barriers on access to care, quality of care and vascular
      morbidity among patients with diabetes and coronary heart disease.
AB  - BACKGROUND: The prevalence and consequences of financial barriers to health care
      among patients with multiple chronic diseases are poorly understood. OBJECTIVE:
      We sought to assess the prevalence of self-reported financial barriers to health
      care among individuals with diabetes and coronary heart disease (CHD) and to
      determine their association with access to care, quality of care and clinical
      outcomes. DESIGN: The 2007 Centers for Disease Control Behavioral Risk Factor
      Surveillance Survey. PARTICIPANTS: Diabetic patients with CHD. MAIN MEASURES:
      Financial barriers to health care were defined by a self-reported time in the
      past 12 months when the respondent needed to see a doctor but could not because
      of cost. The primary clinical outcome was vascular morbidity-a composite of
      stroke, retinopathy, nonhealing foot sores or bilateral foot amputations. KEY
      RESULTS: Among the 11,274 diabetics with CHD, 1,541 (13.7 %) reported financial
      barriers to health care. Compared to individuals without financial barriers,
      those with financial barriers had significantly reduced rates of medical
      assessments within the past 2 years, hemoglobin (Hgb) A1C measurements in the
      past year, cholesterol measurements at any time, eye and foot examinations within
      the past year, diabetic education, antihypertensive treatment, aspirin use and a
      higher prevalence of vascular morbidity. In multivariable analyses, financial
      barriers to health care were independently associated with reduced odds of
      medical checkups (Odds Ratio [OR], 0.61; 95 % Confidence Intervals [CI], 0.55
      0.67), Hgb A1C measurement (OR, 0.85; 95 % CI, 0.77-0.94), cholesterol
      measurement (OR, 0.76; 95 % CI, 0.67-0.86), eye (OR, 0.85; 95 % CI, 0.79-0.92)
      and foot (OR, 0.92; 95 % CI, 0.84-1.00) examinations, diabetic education (OR,
      0.93; 95 % CI, 0.87-0.99), aspirin use (OR, 0.88; 95 % CI, 0.81-0.96) and
      increased odds of vascular morbidity (OR, 1.23; 95 % CI, 1.14-1.33). CONCLUSIONS:
      In diabetic adults with CHD, financial barriers to health care were associated
      with impaired access to medical care, inferior quality of care and greater
      vascular morbidity. Eliminating financial barriers and adherence to guideline
      based recommendations may improve the health of individuals with multiple chronic
      diseases.

PMID- 24078407
TI  - The role of self-efficacy, coping, and lapses in weight maintenance.
AB  - PURPOSE: Successful weight maintenance after weight loss is exceedingly rare. The
      present study aimed to identify psychological predictors of lapses and weight
      maintenance. METHODS: Self-efficacy, coping, and perceptions of lapses were
      examined as potential predictors of lapse frequency and weight maintenance
      (percentage weight loss maintained). Participants included 67 adults (85.3 %
      women) who had intentionally lost a mean of 16 % of their body weight and had
      stopped losing weight at least 6 months prior to data collection. Participants
      completed a 7-day lapse diary tracking the frequency and perceived severity of
      their dietary and activity lapses, along with questionnaires on self-efficacy,
      coping, and characteristics of their weight loss. RESULTS: Participants had lost
      a mean of 13.9 kg, 20.4 months prior to data collection. More frequent lapsing
      was correlated with lower self-efficacy and greater perceived lapse severity.
      Lower percentage of weight loss maintained was correlated with lower self
      efficacy, poorer coping, greater perceived lapse severity, and longer time since
      weight loss ended. "Regainers," who maintained <90 % of their weight loss, had
      poorer self-efficacy, poorer coping, greater lapse frequency, and greater
      perceived lapse severity, than "maintainers," who maintained at least 90 % of
      their weight loss. CONCLUSIONS: The results suggest that self-efficacy, coping,
      and perceived lapse severity are significant predictors of weight maintenance,
      consistent with the relapse prevention model. The goals of improving self
      efficacy and coping skills might be important additions to weight maintenance
      programs.

PMID- 24078408
TI  - Association between CTLA-4 genetic polymorphisms and susceptibility to
      osteosarcoma in Chinese Han population.
AB  - Osteosarcoma (OS) is the most common malignant primary bone tumor in the world.
      The cytotoxic T-lymphocyte antigen-4 gene (CTLA-4) is an important candidate gene
      for influencing the development of OS. This study aimed to investigate the
      potential association of CTLA-4 genetic polymorphisms with OS risk in Chinese Han
      population. A total of 415 OS patients and 431 healthy controls were enrolled in
      this study. The created restriction site-polymerase chain reaction (CRS-PCR) and
      DNA sequencing methods were used to detect the genotyping of CTLA-4 c.75G[C and
      c.326G[A genetic polymorphisms. We observed that the genotypes/alleles of c.75G[C
      and c.326G[A genetic polymorphisms were statistically associated with the
      increased risk of OS (for c.75G[C, CC versus (vs.) GG: OR 1.72, 95% CI 1.09-2.74;
      C vs. G: OR 1.30, 95% CI 1.06-1.60; for c.326G[A, AA vs. GG: OR 2.12, 95% CI 1.31
      3.42; A vs. G: OR 1.31, 95% CI 1.07-1.61). The allele-C/genotype-CC of c.75G[C
      and allele-A/genotype-AA of c.326G[A may contribute to OS susceptibility. These
      data indicate that CTLA-4 genetic polymorphisms are potentially related to OS
      risk in Chinese Han population, and might be used as molecular markers for
      evaluating the risk of OS.

PMID- 24078409
TI  - Moderate to severe nausea in radioactive iodine (RAI) therapy  is associated with
      the RAI dose per body weight  and was not prevented by ramosetron.
AB  - To retrospectively analyze the individual risk factors for radioactive iodine
      (RAI)-associated nausea and vomiting, and to examine the anti-emetic effect of
      ramosetron (5-hydroxytryptamine-3 receptor antagonist) in RAI therapy. Patients
      with differentiated thyroid carcinoma who underwent first-time RAI therapy at
      Nagasaki University Hospital between January 2009 and 2013 were included (N =
      81). As a routine treatment, all patients were administered 30 mg of domperidone
      per day. Patients who underwent RAI therapy between April 2011 and January 2013
      were also administered 0.1 mg of ramosetron per day in addition to domperidone.
      Nausea and vomiting were evaluated based on Common Terminology Criteria for
      Adverse Events version 4.0. RAI-associated nausea and vomiting of any grade were
      seen in 37.0 and 6.2 % of patients in total, respectively. Moderate to severe
      nausea (grade 2-3) was seen in 22.2 % of patients and associated with the dose of
      RAI per body weight (odds ratio = 1.046, p = 0.013), but not with the use of
      ramosetron, in multivariate logistic regression analysis. We have identified the
      dose of RAI per body weight to be an individual risk factor associated with
      moderate to severe RAI-associated nausea. This study failed to show that the
      combined use of ramosetron and domperidone reduced the frequency of RAI
      associated nausea and vomiting.

PMID- 24078410
TI  - Treatment satisfaction and glycemic control in young Type 1 diabetic patients in
      transition from pediatric health care: CSII versus MDI.
AB  - To evaluate whether continuous subcutaneous insulin infusion (CSII) may have any
      advantage over multiple daily injections (MDI) on glycemic control and treatment
      satisfaction in young patients with Type 1 diabetes in transition to an adult
      diabetes center. The study population consisted of 125 patients on MDI; 38 out of
      the 43 patients considered eligible for CSII completed the study and the 82
      remaining on MDI served as control group. Glycemic control and treatment
      satisfaction [diabetes treatment satisfaction questionnaire (DTSQ)] were
      evaluated in all patients at baseline and after 12 weeks. At baseline, the two
      groups were well matched for demographic characteristics and glycemic control.
      DTSQ score was lower in CSII group (21.1 +/- 8.8 vs. 25.1 +/- 7.1, P = 0.011).
      After 12 weeks, a similar decrease in HbA1C was observed in both groups
      [difference -0.3 % (95 % CI-0.6 to 0.1, P = 0.847)]. Mean amplitude glucose
      excursions,blood glucose standard deviation, and overall hypoglycemia were
      significantly reduced in CSII group. DTSQ overall score increased in CSII and
      decreased in MDI (difference between groups = 9.9, 95 % CI 8.0-12.0, P<0.001),
      while perceived hyperglycemia and hypoglycemia decreased in CSII compared with
      MDI (difference:-2.5 and -2.0, respectively, P<0.001 for both). Among young Type
      1 diabetic patients in transition from Pediatrics,CSII showed a similar efficacy
      in reducing HbA1c compared with MDI, with less hypoglycemia and glycemic
      excursions, and was better in improving overall treatment satisfaction and the
      rate of perceived hyperglycemia and hypoglycemia.

PMID- 24078411
TI  - Decrease in TSH levels after lactose restriction in Hashimoto's thyroiditis
      patients with lactose intolerance.
AB  - We aimed to evaluate the prevalence of lactose intolerance (LI) in patients with
      Hashimoto's thyroiditis(HT) and the effects of lactose restriction on thyroid
      function in these patients. Eighty-three HT patients taking L-thyroxine (LT4)
      were enrolled, and lactose tolerance tests were performed on all patients.
      Lactose intolerance was diagnosed in 75.9 % of the patients with HT. Thirty-eight
      patients with LI were started on a lactose-restricted diet for 8 weeks. Thirty
      eight patients with LI (30 euthyroid and 8 with subclinical hypothyroidism), and
      12 patients without LI were included in the final analysis. The level of TSH
      significantly decreased in the euthyroid and subclinical hypothyroid patients
      with LI [from 2.06 +/- 1.02 to 1.51 +/-1.1 IU/mL and from 5.45 +/- 0.74 to 2.25
      +/- 1.88 IU/mL,respectively (both P<0.05)]. However, the level of TSH in patients
      without LI did not change significantly over the 8 weeks (P>0.05). Lactose
      intolerance occurs at a high frequency in HT patients. Lactose restriction leads
      to decreased levels of TSH, and LI should be considered in hypothyroid patients
      who require increasing LT4 doses,have irregular TSH levels and are resistant to
      LT4 treatment.

PMID- 24078414
TI  - Direct access to highly substituted 1-naphthols through palladium-catalyzed
      oxidative annulation of benzoylacetates and internal alkynes.
AB  - One for the pot: 1-Naphthols, well-known structural design elements in medicinal
      chemistry, were readily prepared by means of a one-pot palladium-catalyzed
      oxidative annulation of readily available benzoylacetates to internal alkynes. 

PMID- 24078415
TI  - Evolution of a multicomponent system: computational and mechanistic studies on
      the chemo- and stereoselectivity of a divergent process.
AB  - The evolution of a ternary molecular system (imine, diene and nitrile) is
      analyzed to disclose the pathways leading to a divergent synthetic outcome. The
      Lewis acid catalyzed reaction between cyclohexadiene, 2-phenyl-indol-3-one and
      acetonitrile yields the imino-Diels-Alder adduct as the major product together
      with minor amounts of the Mannich-Ritter-amidine product. The experimental and
      computational data show that the relative orientation of the initial reactants
      dictates the synthetic outcome. The exo approach between imine and diene leads to
      the Diels-Alder adduct in a concerted process, whereas the endo mode leads to a
      polarized intermediate, which is trapped by acetonitrile to yield the
      multicomponent adduct. 

PMID- 24078416
TI  - Recurrent embolic events after PFO closure: how often and why?

PMID- 24078417
TI  - Pulmonary vein stenosis: recognizing an important cause of dyspnea after
      pulmonary vein isolation.

PMID- 24078418
TI  - Take it out, still in doubt?

PMID- 24078419
TI  - Thromboaspiration and IIb/IIIa therapy in STEMI: abciximab redux?

PMID- 24078420
TI  - What is a cardiologist to do: and it can only get better.

PMID- 24078421
TI  - Perioperative MI: is there a clot or not?

PMID- 24078422
TI  - Balloon aortic valvuloplasty to stabilize patients prior to aortic valve
      replacement: strategy of the future or a bridge to the past?

PMID- 24078423
TI  - Transcatheter aortic valve implantation in the real world: a lesson in sharing
      the sandbox.

PMID- 24078424
TI  - Squeezing TAVR into a very narrow funnel.

PMID- 24078425
TI  - TAVR technology-size matters!

PMID- 24078427
TI  - Infectious Complications of Mechanical Circulatory Support (MCS) Devices.
AB  - Left-ventricular assist devices and other forms of mechanical circulatory support
      are increasingly important in the routine therapy of patients with end-stage
      congestive heart failure. Technology may help to decrease the rate of infections
      associated with these devices, but with larger numbers of implants being utilized
      across the globe, infections overall are becoming more commonplace. Becoming
      familiar with appropriate techniques for prevention and with the ideal approach
      to diagnostic and therapeutic strategies is key to managing mechanical
      circulatory support infections in this unique, but growing, patient population.

PMID- 24078426
TI  - Squamous cell/adenosquamous carcinomas and adenocarcinomas of the gallbladder: an
      immunohistochemistry study of prognostic markers.
AB  - Gallbladder cancers (GBCs) are highly aggressive and lethal diseases. However,
      the key molecular mechanisms responsible for the progression and prognosis of
      GBCs have not been identified. No biological markers for effectively identifying
      GBC subtypes have been reported. In this study the expression of keratin 19
      (KRT19) and human achaete-scute homolog 1 (hASH1) proteins in 46 squamous
      cell/adenosquamous carcinomas (SC/ASC) and 80 adenocarcinomas (AC) were examined
      using immunohistochemistry. Negative KRT19 or positive hASH1 expression were
      significantly associated with lymph node metastasis, invasion and TNM stage of
      SC/ASC patients. In contrast, positive KRT19 and hASH1 expression were
      significantly associated with large tumor size, lymph metastasis, invasion, and
      TNM stage in AC patients. Univariate Kaplan-Meier analysis showed that loss of
      KRT19 or elevated hASH1 expression significantly correlated with decreased
      survival in SC/ASC patients. In contrast, positive KRT19 and hASH1 expression
      correlated with a shorter survival time in AC patients. Multivariate Cox
      regression analysis showed that negative KRT19 expression or positive hASH1
      expression was an independent poor-prognostic predictor in SC/ASC, but positive
      KRT19 and hASH1 expression were poor-prognostic factors in AC patients. Our study
      suggested that hASH1 can be used to determine the malignancy of SC/ASC and AC
      tumors and is associated with poor prognosis. In contrast, KRT19 is a protective
      factor in AC patients but a sign of malignancy in SC/ASC patients.

PMID- 24078428
TI  - Clinical Experience with Immune Monitoring for Cytomegalovirus in Solid-Organ
      Transplant Recipients.
AB  - Novel strategies are needed to further reduce the burden of cytomegalovirus (CMV)
      disease in solid-organ transplant (SOT) recipients. Measurement of the specific
      cell-mediated immunity against CMV can identify the actual risk for the
      development of CMV disease in a given patient. Thus, immune monitoring is an
      attractive strategy for individualizing the management of CMV after
      transplantation. A growing number of observational studies on immune monitoring
      for CMV have been published over recent years, although there is a lack of data
      coming from interventional trials. In high-risk patients, measurement of CMV
      specific T-cell responses appropriately stratifies the risk of CMV disease after
      discontinuation of antiviral prophylaxis. Immune monitoring may also help to
      identify patients followed by the preemptive approach at low risk for progression
      to CMV disease. Pretransplant assessment of cell-mediated immunity in
      seropositive patients may predict the development of posttransplant CMV
      infection. Overall, these studies indicate that the use of cell-mediated immunity
      assays has the potential to improve the management of CMV disease in SOT
      recipients.

PMID- 24078429
TI  - Crystalline bone marrow in systemic oxalosis.

PMID- 24078430
TI  - Re: Nuchal translucency and major congenital heart defects in fetuses with normal
      karyotype: a meta-analysis. A. Sotiriadis, S. Papatheodorou, M. Eleftheriades and
      G. Makrydimas. Ultrasound Obstet Gynecol 2013; 42: 383-389.

PMID- 24078431
TI  - Re: Three-dimensional fetal echocardiography for prediction of postnatal surgical
      approach in double outlet right ventricle: a pilot study. V. Zidere, K.
      Pushparajah, L. D. Allan and J. M. Simpson. Ultrasound Obstet Gynecol 2013; 42:
      421-425.

PMID- 24078435
TI  - New eremophilane-type sesquiterpenes from an Antarctic deepsea  derived fungus,
      Penicillium sp. PR19 N-1.
AB  - Chemical investigation of an Antarctic deepsea derived fungus Penicillium sp.
      PR19 N-1 yielded five new eremophilane-type sesquiterpenes 1-5 and a new rare
      lactam-type eremophilane 6, together with three known compounds 7-9. The
      structures of these diverse sesquiterpenes were determined by extensive NMR and
      mass spectroscopic analyses. Compounds 1, 2, 4-6, 8 and 9 were evaluated for
      their cytotoxities against HL-60 and A-549 human cancer cell lines, and 5 was the
      most active one with IC50 value of 5.2 lM against the A-549 cells.

PMID- 24078432
TI  - Perinatal morbidity and mortality in early-onset fetal growth restriction: cohort
      outcomes of the trial of randomized umbilical and fetal flow in Europe (TRUFFLE).
AB  - OBJECTIVES: Few data exist for counseling and perinatal management of women after
      an antenatal diagnosis of early-onset fetal growth restriction. Yet, the
      consequences of preterm delivery and its attendant morbidity for both mother and
      baby are far reaching. The objective of this study was to describe perinatal
      morbidity and mortality following early-onset fetal growth restriction based on
      time of antenatal diagnosis and delivery. METHODS: We report cohort outcomes for
      a prospective multicenter randomized management study of fetal growth restriction
      (Trial of Randomized Umbilical and Fetal Flow in Europe (TRUFFLE)) performed in
      20 European perinatal centers between 2005 and 2010. Women with a singleton fetus
      at 26-32 weeks of gestation, with abdominal circumference < 10(th) percentile and
      umbilical artery Doppler pulsatility index > 95(th) percentile, were recruited.
      The main outcome measure was a composite of fetal or neonatal death or severe
      morbidity: survival to discharge with severe brain injury, bronchopulmonary
      dysplasia, proven neonatal sepsis or necrotizing enterocolitis. RESULTS: Five
      hundred and three of 542 eligible women formed the study group. Mean +/- SD
      gestational age at diagnosis was 29 +/- 1.6 weeks and mean +/- SD estimated fetal
      weight was 881 +/- 217 g; 12 (2.4%) babies died in utero. Gestational age at
      delivery was 30.7 +/- 2.3 weeks, and birth weight was 1013 +/- 321 g. Overall,
      81% of deliveries were indicated by fetal condition and 97% were by Cesarean
      section. Of 491 liveborn babies, outcomes were available for 490 amongst whom
      there were 27 (5.5%) deaths and 118 (24%) babies suffered severe morbidity. These
      babies were smaller at birth (867 +/- 251 g) and born earlier (29.6 +/- 2.0
      weeks). Death and severe morbidity were significantly related to gestational age,
      both at study entry and delivery and also with the presence of maternal
      hypertensive morbidity. The median time to delivery was 13 days for women without
      hypertension, 8 days for those with gestational hypertension, 4 days for pre
      eclampsia and 3 days for HELLP syndrome. CONCLUSIONS: Fetal outcome in this study
      was better than expected from contemporary reports: perinatal death was uncommon
      (8%) and 70% survived without severe neonatal morbidity. The intervals to
      delivery, death and severe morbidity were related to the presence and severity of
      maternal hypertensive conditions.

PMID- 24078436
TI  - Familial isolated pituitary adenoma caused by a Aip gene mutation not described
      before in a family context.
AB  - The cause of familial isolated pituitary adenomas (FIPA) remains unknown in a
      high percentage of cases, but the AIP gene plays an important role in the
      etiology. The aim of the study is to describe a family with FIPA syndrome and the
      results of genomic studies. A 16-year-old man had a giant prolactinoma resistant
      tomedical treatment with delayed growth and pubertal development. His mother had
      been previously diagnosed with a nonfunctioning pituitary macroadenoma.
      Transsphenoidal endoscopic resection was performed and a genetic study revealed a
      heterozygous mutation in exon 6: 974G>A (p.Arg325Gln). Because the AIP gene is a
      tumor suppressor gene, we searched for loss of heterozygosity within the AIP gene
      by amplifying exon 6 from tumor tissue of the patient. In the electropherogram,
      only the A allele was amplified (hemizygous state), indicating loss of the normal
      allele. We report a Spanish family with FIPA in whom a mutation in the AIP gene
      previously unreported in a familiar context was identified.

PMID- 24078437
TI  - Family-based treatment without a family: case report  of an adolescent with
      anorexia nervosa.

PMID- 24078440
TI  - Iatrogenic fungal infections of central nervous system.
AB  - Iatrogenic fungal infections of the central nervous system had been considered a
      medical curiosity. Generally, they are a rare isolated complication of
      neurosurgical procedures, but periodically these infections are observed in
      larger populations as a result of exposure to contaminated materials during
      diagnostic or therapeutic procedures. In the last year, an epidemic of iatrogenic
      fungal central nervous system disease accompanied the use of fungal-contaminated
      compounded methylprednisolone distributed by one facility, heightening the
      attention given to this infectious disorder. As of May 6, 2013, 758 individuals
      from 20 US states have developed meningitis and/or spinal or paraspinal infection
      because of contaminated methylprednisolone from the New England Compounding
      Center in Framingham, Massachusetts, and 58 deaths have been reported. A total of
      12 different fungi have been identified; Exserohilum rostratum, a filamentous
      environmental fungus rarely associated with human disease previously, has been
      the most commonly isolated pathogen. Meningitis has dominated the clinical
      presentation, accounting for more than half of the cases, but spinal and
      paraspinal infections, arachnoiditis, and stroke have also been observed. The
      diagnosis can be challenging as the organisms may be fastidious. An assay for
      beta-D-glycan has been proposed as an effective adjunctive test for E. rostratum
      infection. The current therapeutic recommendation is a 6 mg/kg dose of
      voriconazole every 12 h followed by liposomal amphotericin B. In some instances,
      surgical debridement and drainage may be necessary.

PMID- 24078438
TI  - Metabolic and storage lung diseases: spectrum of imaging appearances.
AB  - : Metabolic and storage diseases constitute a heterogeneous group of disorders
      that occur in the setting of altered biochemical homeostasis. Many of these
      disorders affect the lungs, either exclusively or as part of a systemic syndrome.
      For example, amyloidosis can be limited to the tracheobronchial tree or involve
      the kidneys, lungs and heart. The indolent course of some of these disorders and
      the non-specific clinical symptoms often result in a diagnostic challenge.
      Imaging, particularly high-resolution computed tomography (HRCT), is an
      invaluable asset in the diagnosis of these clinical conditions. Some metabolic
      and storage diseases have characteristic HRCT appearances, helping narrow the
      differential diagnosis. Correlation of the radiological and histopathological
      findings of this group of diseases has also helped improve understanding of these
      disorders. In addition, CT can offer guidance when tissue sampling is warranted
      and aid in histopathological diagnosis. This article describes the pertinent
      clinical features of the more common metabolic and storage diseases affecting the
      lungs, illustrates their respective HRCT findings and provides the relevant
      differential diagnosis. TEACHING POINTS: * To recognise the various metabolic and
      storage lung diseases * To identify the characteristic imaging findings in
      various metabolic and storage lung diseases * To discuss the relevant
      differential diagnoses of each of these diseases.

PMID- 24078441
TI  - The bone anabolic therapy.
AB  - Teriparatide (TPTD), the amino-terminal parathyroid hormone recombinant peptide
      [PTH (1-34)], is a drug with a proven anabolic action on the bone, effective in
      preventing vertebral and non-vertebral fragility fractures. Recent publications
      have investigated in great detail the TPTD action on the cortical bone,
      highlighting the increased strength in the critical zone of the hip with high
      risk of fracture in osteoporotic patients Poole (PLoS ONE 6:e16190, 2011). In
      November 2002, TPTD was approved by the FDA for use in post-menopausal women and
      men with osteoporosis at high risk of fracture and in patients with
      glucocorticoid-induced osteoporosis and, since then, has been used to treat more
      than 1 million patients worldwide (J Bone Miner Res 27(12):2429-2437, 2012). The
      unchanged safety profile and the well-known mechanism of action of this drug have
      led doctors to explore the use of TPTD in other conditions such as delayed
      fracture healing, non-union, osteonecrosis of the jaw, etc. The positive reports
      that have resulted from these studies are helping to hypothesize a new
      perspective on the wider use of this drug, but warrant further clinical
      investigation to consolidate these results.

PMID- 24078442
TI  - The relationship between age and the intraoperative  complication rate during
      phacoemulsification surgery.
AB  - AIM: The aim of this study was to determine if aging is a factor that increases
      the intraoperative complication rate during phacoemulsification surgery.
      MATERIALS AND METHODS: Patients who underwent phacoemulsification surgery were
      divided into three age groups according to World Health Organization
      classification, as follows: <= 59, 60-74, and >= 75 years. The intraoperative
      complications which occurred during the operation were recorded. Binary logistics
      regression analysis, Pearson's correlation analysis, and Duncan's (multiple
      range) test were used for statistical analysis. RESULTS: In total, 789 patients
      who underwent phacoemulsification surgery at Nigde State Hospital, Ophthalmology
      Clinic between 01 July 2010 and 31 October 2012 were retrospectively reviewed,
      and intraoperative complications that occurred during surgery were recorded. Mean
      age of the patients was 68.98 years (range 38-93 years). In all, 132 (16.7 %)
      patients were aged <= 59 years, 406 (51.5 %) were aged 60 - 74 years, and 251
      (31.8 %) were aged >= 75 years. The complication rates were 3.78 % in the <= 59
      year-old age group, 5.17 % in the 60- to 74-year-old age group, and 5.30 % in the
      >= 75-year-old age group. Age did not have a significant effect on intraoperative
      complication rates during phacoemulsification surgery, according to binary
      logistic regression analysis (P = 0.58) and Pearson's correlation analysis (P =
      0.076). The incidence and risk of intraoperative complications in the age groups
      did not differ statistically (Duncan's test, P = 0.18). CONCLUSION: Age has no
      effect on the rate of intraoperative complications during phacoemulsification
      surgery.

PMID- 24078443
TI  - Batch tautomer generation with MolTPC.
AB  - Besides all their conformational degrees of freedom, drug-like molecules and
      natural products often also undergo tautomeric interconversions. Compared to the
      huge efforts made in experimental investigation of tautomerism, open and free
      algorithmic solutions for prototropic tautomer generation are surprisingly rare.
      The few freely available software packages limit their output to a subset of the
      possible configurational space by sometimes unwanted prior assumptions and
      complete neglection of ring-chain tautomerism. Here, we describe an adjustable
      fully automatic tautomer enumeration approach, which is freely available and also
      incorporates the detection of ring-chain variants. The algorithm is implemented
      in the MolTPC framework and accessible on SourceForge.

PMID- 24078446
TI  - Artemisinin inhibits gastric cancer cell proliferation through upregulation of
      p53.
AB  - Recent population studies suggest that the use of artemisinin is associated with
      reduced incidence and improved prognosis of certain cancers. In the current
      study, we assessed the effect of artemisinin on gastric cancer cells (AGS and
      MKN74 cells). We found that artemisinin inhibited growth and modulated expression
      of cell-cycle regulators in these cells. Treatment with artemisinin was also
      associated with induction of p27 kip1 and p21 kip1, two negative cell-cycle
      regulators. Furthermore, we revealed that artemisinin treatment led to an
      increased expression of p53. Taken together, these results provide evidence for a
      mechanism that may contribute to the antineoplastic effects of artemisinin
      suggested by recent population studies and justify further work to explore
      potential roles for it in gastric cancer prevention and treatment.

PMID- 24078447
TI  - ASAP3 expression in non-small cell lung cancer: association with cancer
      development and patients' clinical outcome.
AB  - ASAP3 belongs to Arf-specific GTPase-activating proteins which regulate Arfs by
      stimulating their intrinsic GTP hydrolysis. ASAP3 expression and the clinical
      significance in malignant tumors are largely unknown. In this study, we examined
      ASAP3 expression in non-small cell lung cancer (NSCLC) to find out its
      clinicopathological significance. Immunohistochemistry shows elevated expression
      of ASAP3 in cancer tissues (54.8 % (57/104)) compared to normal lung tissues
      (18.0 % (9/50)) (p < 0.05). Increased ASAP3 expression was associated with poor
      differentiation, lymph node metastasis, and advanced TNM stages in NSCLC (p <
      0.05). Survival analysis reveals that ASAP3 expression contributes to patients'
      poor clinical outcome (p < 0.05). We also examined ASAP3 expression in several
      lung cancer cell lines using Western blotting. We downregulated ASAP3 expression
      in LTE cell which has a relative high level of ASAP3 expression using siRNA and
      found that reduced ASAP3 leads to significant inhibition of cancer cell invasion
      (p < 0.05). These data indicate that ASAP3 is elevated in NSCLC and may
      contribute to cancer development and patients' poor clinical outcome, which is
      possibly due to its critical roles in regulating cancer invasion.

PMID- 24078448
TI  - miR-34 is associated with poor prognosis of patients with gallbladder cancer
      through regulating telomere length in tumor stem cells.
AB  - miR-34a has been identified as a tumor suppressor in several tumors, but its
      involvement in gallbladder cancer (GBC) has not been reported. In this study, the
      miR-34a level and telomere length were measured in 77 gallbladder adenocarcinomas
      and 36 peritumoral tissues by real-time PCR. Forced miR-34a expression was
      established by an adenovirus carrying a miR-34a expression cassette. The colony
      forming ability of isolated CD44+CD133+ GBC tumor stem-like cells was measured by
      matrigel colony assay. The xenograft tumor models were established by inoculating
      nude mice with CD44+CD133+cells. Results showed that significantly lower miR-34a
      expression and longer telomere length were observed in gallbladder adenocarcinoma
      tissues, which correlated with poor prognosis of GBC patients. Forced
      overexpression of miR-34a inhibited the colony-forming ability of CD44+CD133+ GBC
      tumor stem-like cells in vitro and xenograft tumor growth in vivo. Injection of
      Ad-miR-34a downregulated PNUTS expression and reduced telomere length in
      xenograft GBC tumor cells. In conclusion, miR-34a is a tumor suppressor in
      gallbladder cancer. Both low miR-34a expression and long telomere length are
      markers for poor prognosis of patients with gallbladder adenocarcinoma. Our study
      also suggests that the miR-34a gene could be a target for targeting therapy of
      GBC.

PMID- 24078449
TI  - Prognostic significance of VEGF-C immunohistochemical expression in breast
      cancer: a meta-analysis.
AB  - Vascular endothelial growth factor-C (VEGF-C) is considered as a prime mediator
      of lymphangiogenesis and has been implicated in carcinogenesis and metastasis.
      Various studies examined the relationship between VEGF-C protein overexpression
      with the clinical outcome in patients with breast cancer but yielded conflicting
      results. Electronic databases updated to April 2013 were searched to find
      relevant studies. A meta-analysis was conducted with eligible studies which
      quantitatively evaluated the relationship between VEGF-C overexpression and
      survival of patients with breast cancer. Survival data were aggregated and
      quantitatively analyzed. We performed a meta-analysis of 11 studies (n = 1,357
      patients) that evaluated the correlation between VEGF-C overexpression detected
      by immunohistochemistry and survival in patients with breast cancer. Combined
      hazard ratios suggested that VEGF-C overexpression was not associated with poor
      prognosis of disease-free survival (HR [hazard ratio] = 0.80, 95 % CI [confidence
      interval]: 0.51-1.09), overall survival (OS) (HR = 1.08, 95 % CI: 0.37-1.78) in
      patients with breast cancer. In the stratified analysis by patient source,
      significantly risks were not found among Asians or non-Asians. No significant
      heterogeneity was observed among all studies. VEGF-C overexpression was not
      associated with poor disease-free survival or overall survival in breast cancer.

PMID- 24078450
TI  - TP53 immunohistochemical expression is associated with the poor outcome for
      hepatocellular carcinoma: evidence from a meta-analysis.
AB  - Various studies examined the relationship between p53 expression with the
      clinical outcome in patients with hepatocellular carcinoma (HCC), but yielded
      conflicting results. Electronic databases updated to July 2013 were searched to
      find relevant studies. A meta-analysis was conducted with eligible studies which
      quantitatively evaluated the relationship between p53 expression and survival of
      patients with HCC. Survival data were aggregated and quantitatively analyzed. We
      performed a meta-analysis of 24 studies that evaluated the correlation between
      p53 expression and survival in patients with HCC. Combined hazard ratios
      suggested that p53 expression had an unfavorable impact on overall survival (OS)
      (HR (hazard ratio) = 1.55, 95 % CI (confidence interval) 1.36-1.74) and disease
      free survival (DFS) (HR = 1.54, 95 % CI 1.21-1.88) in patients with HCC. No
      significant heterogeneity was observed among 20 studies for OS (P = 0.786) and
      among 11 studies for DFS (P = 0.698). P53 expression indicates a poor prognosis
      for patients with hepatocellular carcinoma.

PMID- 24078451
TI  - Methylenetetrahydrofolate reductase polymorphisms and breast cancer risk in
      Chinese population: a meta-analysis of 22 case-control studies.
AB  - The association between methylenetetrahydrofolate reductase (MTHFR) gene
      polymorphisms and breast cancer risk in the Chinese population has been widely
      reported, but results were inconsistent. In order to derive a more precise
      estimation of the relationship, a meta-analysis was performed. Eligible articles
      were identified through search of databases including Medline, PubMed, Web of
      Science, Embase, Chinese Biomedical Literature Database (CBM, Chinese), China
      National Knowledge Infrastructure (CNKI, Chinese), and Wangfang Database
      (Chinese). The association between the MTHFR polymorphism and breast cancer risk
      was conducted using odds ratios (ORs) and 95 % confidence intervals (95 % CIs).
      Finally, a total of 22 studies with 6,103 cases and 7,913 controls were included
      in our meta-analysis: 13 studies with 3,273 cases and 4,419 controls for C677T
      polymorphism and 9 studies with 2,830 cases and 3,494 controls for A1298C
      polymorphism. With regard to C677T polymorphism, significant association was
      found with breast cancer risk under three models (T vs. C: OR = 1.12, 95 % CI =
      1.02-1.23, P = 0.015; TT vs. CC: OR = 1.35, 95 % CI = 1.10-1.67, P = 0.005; TT
      vs. CC/CT: OR = 1.37, 95 % CI = 1.11-1.70, P = 0.004). There was no significant
      association found between A1298C polymorphism and breast cancer risk under all
      genetic models (C vs. A: OR = 0.96, 95 % CI = 0.89-1.03, P = 0.268; CC vs. AA: OR
      = 0.98, 95 % CI = 0.77-1.26, P = 0.899; AC vs. AA: OR = 0.95, 95 % CI = 0.88
      1.02, P = 0.174; CC vs. AC/AA: OR = 1.00, 95 % CI = 0.78-1.28, P = 0.996, CC/AC
      vs. AA: OR = 0.96, 95 % CI = 0.89-1.02, P = 0.196). In summary, during this meta
      analysis, we found that MTHFR C677T polymorphism was significantly associated
      with breast cancer risk in the Chinese population. Meanwhile, MTHFR A1298C
      polymorphism was not associated with breast cancer risk in the Chinese
      population.

PMID- 24078452
TI  - The VDR gene FokI polymorphism and ovarian cancer risk.
AB  - The polymorphism of vitamin D receptor (VDR) gene is demonstrated to affect the
      activity of its encoding protein and the subsequent downstream effects mediated
      by vitamin D. Mutations in VDR gene FokI have been suggested in the development
      of various cancers. Whether the polymorphism of the VDR gene FokI confers risk to
      ovarian cancer still remains controversial across the published studies in
      different ethnicity. The aim of this meta-analysis was to determine the role of
      VDR gene FokI variant in the susceptibility to ovarian cancer. Six publications
      with 14 individual case-control studies involving a total of 10,964 subjects were
      finally included into our study after a comprehensive literature search of the
      PubMed, Embase, Web of Science, and Wanfang databases. The strength of the
      association between the VDR gene FokI polymorphism and ovarian cancer risk was
      estimated under the allelic (T vs. C), homozygous (TT vs. CC), additive (CT vs.
      CC), recessive (TT vs. CC + CT), and dominant (CT + TT vs. CC) gene models. The
      overall odds ratios (ORs) for the contrast models of T vs. C, TT vs. CC, CT vs.
      CC, and CT + TT vs. CC indicated that the VDR gene FokI variant was related to an
      increased risk of ovarian cancer (OR(T vs. C) = 1.09, 95 % confidence interval
      (CI) 1.03-1.15, P(OR) = 0.004; OR(TT vs. CC) = 1.17, 95 % CI 1.04-1.32, P(OR) =
      0.011; OR(CT vs. CC) = 1.10, 95 % CI 1.01-1.20, P(OR) = 0.027; OR(CT + TT vs. CC)
      = 1.12, 95 % CI 1.03-1.21, P(OR) = 0.007). The stratified analysis among the
      Caucasians also identified a significant association between the VDR gene FokI
      polymorphism and the susceptibility to ovarian cancer. The present meta-analysis
      with large available published data has revealed that the VDR gene FokI
      polymorphism confers susceptibility to ovarian cancer, particularly among the
      Caucasian population.

PMID- 24078456
TI  - Tricuspid valve endocarditis complicated by septic pulmonary embolism in an
      intravenous drug user.

PMID- 24078453
TI  - Cell-based reparative therapies for multiple sclerosis.
AB  - The strong rationale for cell-based therapy in multiple sclerosis is based on the
      ability of stem and precursor cells of neural and mesenchymal origin to attenuate
      neuroinflammation, to facilitate endogenous repair processes, and to participate
      directly in remyelination, if directed towards a myelin-forming fate. However,
      there are still major gaps in knowledge regarding induction of repair in chronic
      multiple sclerosis lesions, and whether transplanted cells can overcome the
      multiple environmental inhibitory factors which underlie the failure of
      endogenous repair. Major challenges in clinical translation include the
      determination of the optimal cellular platform, the route of cell delivery, and
      candidate patients for treatment. 

PMID- 24078457
TI  - Novel CT-guided coil localization of peripheral pulmonary nodules prior to video
      assisted thoracoscopic surgery: a pilot study.
AB  - BACKGROUND: Small peripheral lung nodules detected on computed tomography (CT)
      scans are often difficult to find during thoracoscopic resection, and the present
      localizing techniques are inefficient or impractical. PURPOSE: To evaluate a
      novel marking procedure for small peripheral pulmonary nodules using an
      embolization coil. MATERIAL AND METHODS: Patients with small peripheral pulmonary
      nodules underwent preoperative CT-guided nodule localization using an
      embolization coil and then resection by fluoroscopically-guided video-assisted
      thoracoscopic surgery (VATS; group A, n = 22), or, underwent conventional VATS
      without prior location procedures (group B, n = 16). Comparisons were made
      between group A and group B concerning operative time, hospitalization,
      postoperative drainage, and complications. Histopathological diagnoses were made
      immediately after resection of pulmonary nodules. RESULTS: All CT-guided
      embolization coil fixations were successful. No patient in group A and eight
      (50%) in group B required conversion to open thoracotomy (P < 0.0001). No severe
      complications occurred in either group. Compared with group B, group A had a
      significantly shorter mean operative time and hospitalization, and less
      postoperative drainage. CONCLUSION: Preoperative localization of small peripheral
      pulmonary nodules using CT-guided embolization coil insertion and subsequent
      fluoroscopically-guided VATS resection is safer and more effective than
      conventional VATS.

PMID- 24078458
TI  - Continuously moving table aorto-iliofemoral run-off contrast-enhanced magnetic
      resonance angiography: image quality analysis in comparison to the multistep
      acquisition.
AB  - BACKGROUND: Optimal vessel contrast is a prerequisite for vascular imaging.
      Consecutive stationary imaging of multiple fields of view is contrary to the
      continuous contrast material passage through the vascular tree. A continuous
      acquisition of a magnetic resonance (MR) sequence might overcome this limitation.
      PURPOSE: To investigate the image quality of a continuously moving table (CMT)
      acquisition compared with the established multistep approach for contrast
      enhanced magnetic resonance angiography (CE-MRA) of the aorto-iliofemoral run
      off. MATERIAL AND METHODS: Institutional review board approved this retrospective
      interindividual study of 60 consecutive patients referred to CE-MRA for
      peripheral arterial disease. Thirty patients underwent CE-MRA using the routine
      multistep acquisition and 30 patients were scanned using the CMT technique at 1.5
      Tesla. All patients received a fixed contrast dose of 25 mL gadoterate meglumine.
      A quantitative analysis was performed to assess the relative contrast of 10
      vascular segments from the proximal abdominal aorta to the distal calf arteries.
      A qualitative evaluation of three separate vascular regions (abdomen and pelvis,
      thighs, and calves) was performed. Two radiologists graded independently arterial
      vessel conspicuity, venous contamination, presence of artifacts, and diagnostic
      confidence on a 4-point scale. Overall scan time, including all localizer scans,
      was recorded. Statistical differences were tested using the Wilcoxon signed-rank
      test with Bonferroni correction. RESULTS: No significant differences were found
      between the continuously moving table acquisition and the multistep acquisition
      with regard to the relative vascular contrast and the qualitative image criteria.
      The agreement between both readers was significant (Kendall tau rank correlation
      coefficient, 0.373). The absolute reader agreement was 71.4%. The mean overall
      scan time was 12 min 44 s for the CMT protocol and 21 min 41 s for the multistep
      protocol. CONCLUSION: Aorto-iliofemoral run-off CE-MRA acquired with CMT
      technique provides a high image quality equivalent to a multistep technique at an
      overall scan time reduction of 41.3%.

PMID- 24078459
TI  - Reproducibility of manual and semi-automated late enhancement quantification in
      patients with Fabry disease.
AB  - BACKGROUND: Late enhancement (LE) imaging is increasingly used for diagnosis of
      non-ischemic cardiomyopathy. However, the mostly patchy appearance of LE in this
      context may reduce the reproducibility of LE measurement. PURPOSE: To report
      intra- and inter-observer variabilities of LE measurements in Fabry disease using
      manual and semi-automated quantification. MATERIAL AND METHODS: Twenty MRI data
      sets of male patients aged 44 +/- 7 years were analyzed twice (interval 12
      months) by one observer and additionally once by a second observer. Left
      ventricular (LV) parameters were determined using cine MRI. Gradient-echo LE
      images were analyzed by manual planimetry and by a semi-automatic prototype
      software. Variabilities were determined by Bland-Altman analyses and additionally
      intra-class correlation coefficient (ICC) values were calculated to survey intra-
      and inter-observer reproducibility. RESULTS: The amount of LE was 5.2 +/- 5.1 mL
      or 2.8 +/- 2.6 % of LV mass (observer 2). LE was detected predominantly
      intramurally in a patchy pattern. All patients had LE restricted to the basal
      infero-lateral parts of the LV. The extent of LE correlated to LV mass (207 +/-
      70 g, P < 0.05, r = 0.6). The intra- and inter-observer variabilities were -0.6
      to 1.0 mL and -0.7 to 1.6 mL, respectively (95% confidence intervals). ICC values
      were 0.981-0.999. The semi-automatic software allowed quantification of LE areas
      in all patients. The comparison of LE amount determined by semi-automatic
      software versus manual planimetry yielded an intra-observer variability ranging
      from -1.9 to 2.3 mL. CONCLUSION: Semi-automatic planimetry of patchy LE in
      patients with Fabry disease is feasible. The determined intra- and inter-observer
      variabilities for manual and semi-automatic planimetry were in the range of 20
      40% of LE amount with high ICC values.

PMID- 24078460
TI  - Unmet needs and research challenges for late-life  mood disorders.
AB  - Mood disorders are common and often under-recognised in older people whereby,
      together with the general ageing of the population, they are becoming a
      significant and growing public health problem worldwide. However, the need to
      address the problem of late life mood disorders in a real-world setting is met
      with a surprising lack of strong evidence in this field. Randomised clinical
      trials which focus on elderly mood disorders are not very common and the majority
      of them focus on pharmacological treatment of major depression. The aim of this
      study was to review first the main unmet needs and research challenges in late
      life mood disorders as a basis to then review the state of the art evidence
      resulting from randomised clinical trials and the main critical aspects of their
      implementation. Comorbidity as well as polypharmacy, cognitive decline,
      unpredictable placebo response, and uncertainty on optimal duration of trials are
      some of the challenges the investigator has to address. Moreover, some
      methodological limitations of randomised clinical trials reduce the applicability
      of the results of such studies to common clinical practices and have encouraged
      some authors to investigate the existence of possible alternative research
      designs such as pragmatic randomised clinical trials.

PMID- 24078461
TI  - Cysteine (C)-X-C Receptor 4 Regulates NADPH Oxidase-2 During Oxidative Stress in
      Prostate Cancer Cells.
AB  - Reactive oxygen species (ROS) are implicated in many human diseases, including
      cancer. We have previously demonstrated that ROS increased the expression and
      activity of the chemokine receptor, CXCR4, which enhanced metastatic functions in
      prostate cancer cells. Studies have also revealed that CXCR4 and its ligand, SDF
      1alpha, promoted ROS accumulation; however the source of ROS was not
      investigated. Recent evidence suggested that ROS accumulation in prostate cancer
      cell lines was contributed by the NADPH oxidase (NOX) family of enzymes. Herein,
      we sought to determine whether the CXCR4/SDF-1alpha signaling axis mediates ROS
      production through NOX in prostate cancer. We observed an increase in
      intracellular ROS generation in prostate cancer cells upon SDF-1alpha stimulation
      compared to untreated samples. Conversely, lower levels of ROS were detected in
      cells treated with AMD3100 (CXCR4 antagonist) or the ROS scavenger, N-acetyl
      cysteine (NAC). Markedly reduced levels of ROS were observed in cells treated
      with apocynin (NOX inhibitor) compared to rotenone (mitochondrial complex I
      inhibitor)-treated cells. Specifically, we determined that NOX2 responded to, and
      was regulated by, the SDF-1alpha/CXCR4 signaling axis. Moreover, chemical
      inhibition of the ERK1/2 and PI3K pathways revealed that PI3K/AKT signaling
      participated in CXCR4-mediated NOX activity, and that these collective signaling
      events resulted in enhanced cell movement towards a chemoattractant. Finally,
      NOX2 may be a potential therapeutic target, as Oncomine microarray database
      analysis of normal prostate, benign prostatic hyperplasia (BPH) and prostatic
      intraepithelial neoplasia (PIN) tissue samples determined a correlation between
      NOX2 expression and prostate cancer. Taken together, these results suggest that
      CXCR4/SDF-1alpha-mediated ROS production through NOX2 enzymes may be an emerging
      concept by which chemokine signaling progresses tumorigenesis.

PMID- 24078462
TI  - Optimization of RI-MP2 auxiliary basis functions for 6-31G** and 6-311G** basis
      sets for first-, second-, and third-row elements.
AB  - Auxiliary basis functions for second-order Moller-Plesset perturbation theory
      with resolution-of-identity approximation (RI-MP2) are developed for first-,
      second-, and third-row elements, which are suitable for Pople-type 6-31G** and 6
      311G** basis sets. Atomic-centered Gaussian functions up to the g-type function
      are used for auxiliary basis functions to obtain higher accuracy for molecules
      with the accurate description of bonding properties. The performance of the
      developed auxiliary basis functions were tested and evaluated for 114 small and
      23 large molecules. The developed auxiliary basis functions show much smaller
      energy differences between MP2 and RI-MP2 than other auxiliary basis functions
      used for 6-31G** and 6-311G** basis sets with similar computational costs.

PMID- 24078465
TI  - Oxymatrine induces mitochondria dependent apoptosis in human osteosarcoma
      MNNG/HOS cells through inhibition of PI3K/Akt pathway.
AB  - The cytostatic drug from traditional Chinese medicinal herb has acted as a
      chemotherapeutic agent used in treatment of a wide variety of cancers.
      Oxymatrine, classified as a quinolizidine alkaloid, is a phytochemical product
      derived from Sophora flavescens, and has been reported to possess anticancer
      activities. However, the cancer growth inhibitory effects and molecular
      mechanisms in human osteosarcoma MNNG/HOS cell have not been well studied. In the
      present study, the cytotoxic effects of oxymatrine on MNNG/HOS cells were
      examined by MTT and bromodeoxyuridine (BrdU) incorporation assays. The percentage
      of apoptotic cells and the level of mitochondrial membrane potential (Deltapsi m)
      were assayed by flow cytometry. The levels of apoptosis-related proteins were
      measured by Western blot analysis or enzyme assay Kit. Our results showed that
      treatment with oxymatrine resulted in a significant inhibition of cell
      proliferation and DNA synthesis in a dose-dependent manner, which has been
      attributed to apoptosis. Furthermore, we found that oxymatrine considerably
      inhibited the expression of Bcl-2 whilst increasing that of Bax. This promoted
      mitochondrial dysfunction, leading to the release of cytochrome c from the
      mitochondria to the cytoplasm, as well as the activation of caspase-9 and -3.
      Moreover, addition of oxymatrine to MNNG/HOS cells also attenuated
      phosphatidylinositol 3-kinase (PI3K) /Akt signaling pathway cascade, evidenced by
      the dephosphorylation of P13K and Akt. Likewise, oxymatrine significantly
      suppressed tumor growth in female BALB/C nude mice bearing MNNG/HOS xenograft
      tumors. In addition, no evidence of drug-related toxicity was identified in the
      treated animals by comparing the body weight increase and mortality. Therefore,
      these findings should be useful for understanding the apoptotic cellular
      mechanism mediated by oxymatrine and might offer a therapeutic potential
      advantage for human osteosarcoma chemoprevention or chemotherapy.

PMID- 24078466
TI  - Alternol inhibits migration and invasion of human hepatocellular carcinoma cells
      by targeting epithelial-to-mesenchymal transition.
AB  - Hepatocellular carcinoma (HCC) is the third most common cause of cancer-related
      deaths worldwide. Such deaths are due, in large part, to its propensity to
      metastasize. We have examined the effect of alternol on human HCC cells and the
      underlying molecular mechanism. Therapeutic effects of alternol on cancer cell
      migration and invasion were analyzed with Boyden chamber and wound healing
      assays. Effects of alternol on the levels of various proteins involved in cancer
      cell migration and invasion were determined with gelatin zymography,
      immunofluorescence, and Western blotting. As shown, treatment with alternol has
      resulted in a concentration-dependent inhibition of cell migration and invasion
      of HepG2 cells. The inhibition of HCC invasion by alternol was associated with
      the suppression of MMP-9 expression and reversal of epithelial-to-mesenchymal
      transition (EMT). The above results indicated that alternol has the ability to
      inhibit the migration and invasion of human HCC cells by reversing the process of
      EMT, suggesting that alternol may be developed as an alternative drug for the
      treatment of HCC.

PMID- 24078467
TI  - Anti-Candida albicans biofilm effect of novel heterocyclic compounds.
AB  - OBJECTIVES: The aims of this study were to develop new anti-biofilm drugs,
      examine their activity against Candida albicans biofilm and investigate their
      structure-activity relationship and mechanism of action. METHODS: A series of
      thiazolidinedione and succinimide derivatives were synthesized and their ability
      to inhibit C. albicans biofilm formation and destroy pre-formed biofilm was
      tested. The biofilms' structure, metabolic activity and viability were determined
      by XTT assay and propidium iodide and SYTO 9 live/dead stains combined with
      confocal microscopic analysis. The effect of the most active compounds on cell
      morphology, sterol distribution and cell wall morphology and composition was then
      determined by specific fluorescent stains and transmission electron microscopy.
      RESULTS: Most of the compounds were active at sub-MICs. Elongation of the
      aliphatic side chain resulted in reduced anti-biofilm activity and the sulphur
      atom contributed to biofilm killing, indicating a structure-activity
      relationship. The compounds differed in their effects on biofilm viability, yeast
      to-hyphal form transition, hyphal morphology, cell wall morphology and
      composition, and sterol distribution. The most effective anti-biofilm compounds
      were the thiazolidinedione S8H and the succinimide NA8. CONCLUSIONS: We developed
      novel anti-biofilm agents that both inhibited and destroyed C. albicans biofilm.
      With some further development, these agents might be suitable for therapeutic
      purposes.

PMID- 24078468
TI  - Relative efficacy of cefuroxime versus dicloxacillin as definitive antimicrobial
      therapy in methicillin-susceptible Staphylococcus aureus bacteraemia: a
      propensity-score adjusted retrospective cohort study.
AB  - OBJECTIVES: The objective of the present study was to compare the efficacy of
      cefuroxime with that of dicloxacillin as definitive antimicrobial therapy in
      methicillin-susceptible Staphylococcus aureus bacteraemia (MS-SAB) using a Danish
      bacteraemia database, information on the indication for antimicrobial therapy,
      multivariate adjustment and propensity score (PS) matching. METHODS: This was a
      retrospective cohort study. MS-SAB cases from 1 January 2006 to 31 December 2008
      were included from a total of seven hospitals in the greater Copenhagen area and
      seven hospitals in the North Denmark Region. Information including demographics,
      antimicrobial therapy and clinical condition was obtained. The physician's note
      detailing the indication for starting empirical antimicrobial therapy was given
      special attention. Hazard ratios (HRs) and 95% CIs for 30 day and 90 day
      mortality were calculated using PS-adjusted Cox proportional hazards regression
      analyses. In addition, PS matching was performed. RESULTS: A total of 691
      patients with MS-SAB received either dicloxacillin (n = 368) or cefuroxime (n =
      323) as definitive antimicrobial therapy. Twenty-eight different indications for
      empirical antimicrobial therapy were identified and grouped into eight
      categories. There was no statistically significant difference in 30 day mortality
      between the two groups (HR 1.02, 95% CI 0.68-1.52). Definitive antimicrobial
      therapy with cefuroxime was associated with increased 90 day mortality in a PS
      adjusted multivariate analysis (HR 1.43, 95% CI 1.03-1.98) and in the PS matching
      (OR 1.65, 95% CI 1.06-2.56). Antimicrobial therapy for an indication of 'severe
      infection' was independently associated with 90 day mortality (HR 1.97, 95% CI
      1.19-3.28). CONCLUSIONS: Definitive antimicrobial therapy with cefuroxime was
      associated with significantly higher 90 day mortality than was dicloxacillin
      therapy in patients with MS-SAB.

PMID- 24078469
TI  - Measuring osteoporosis quality: The work of the Joint Commission.
AB  - Recognizing the significant impact of osteoporosis, The Joint Commission has
      worked since 2005 to develop performance measures in osteoporosis across the care
      continuum.This work has led to the development of 3 measures, which may be used
      at any time to meet hospital quality improvement goals. Plans are in place to
      submit to the National Quality Forum for endorsement as national consensus
      standards. The measures were developed under the guidance of a 12 member
      Technical Advisory Panel.

PMID- 24078473
TI  - Human somatic cell nuclear transfer: a scientist's perspective.

PMID- 24078470
TI  - Parathyroid hormone and parathyroid hormone-related protein analogs as therapies
      for osteoporosis.
AB  - Osteoporotic fractures result in significant morbidity and mortality. Anabolic
      agents reverse the negative skeletal balance that characterizes osteoporosis by
      stimulating osteoblast-dependent bone formation to a greater degree than
      osteoclast-dependent bone resorption. Parathyroid hormone (PTH) and parathyroid
      hormone- related protein (PTHrP) are peptide hormones, which have anabolic
      actions when administered intermittently. The only FDA-approved anabolic bone
      agent for the treatment of osteoporosis in the United States is PTH 1-34, or
      teriparatide, administered by daily subcutaneous injections. However, PTH 1-84 is
      also available in Europe. Synthetic human PTHrP 1-36 and a PTHrP 1-34 analog,
      BA058, have also been shown to increase lumbar spine bone density. These agents
      and several other PTH and PTHrP analogs, including some which are not
      administered as injections, continue to be investigated as potential anabolic
      therapies for osteoporosis.

PMID- 24078475
TI  - Suicidal cardiac tamponade by a skewer.

PMID- 24078476
TI  - Maternal folic acid-deficient diet causes congenital malformations in the mouse
      eye.
AB  - BACKGROUND: The eye is a very complex structure derived from the neural tube,
      surface ectoderm, and migratory mesenchyme from a neural crest origin. Because
      structures that evolve from the neural tube may be affected by a folate/folic
      acid (FA) deficiency, the aim of this work was to investigate whether a maternal
      folic acid-deficient diet may cause developmental alterations in the mouse eye.
      METHODS: Female C57BL/6J mice (8 weeks old) were assigned into two different
      folic acid groups for periods ranging between 2 and 16 weeks. Animals were killed
      at gestation day 17. Hepatic folate was analyzed, and the eyes from 287 fetuses
      were macroscopically studied, sectioned and immunolabeled with anti-transforming
      growth factor (TGF)-beta2 and anti-TGF-betaRII. RESULTS: Mice exposed to a FA
      deficient diet exhibited numerous eye macroscopic anomalies, such as anophthalmia
      and microphthalmia. Microscopically, the eye was the most affected organ (43.7%
      of the fetuses). The highest incidence of malformations occurred from the 8th
      week onward. A statistically significant linear association between the number of
      maternal weeks on the FA-deficient diet and embryonic microscopic eye
      malformations was observed. The optic cup derivatives and structures forming the
      eye anterior segment showed severe abnormalities. In addition, TGF-beta2 and TGF
      betaRII expression in the eye was also altered. CONCLUSION: This study suggests
      that an adequate folic acid/folate status plays a key role in the formation of
      ocular tissues and structures, whereas a vitamin deficiency is negatively
      associated with a normal eye development even after a short-term exposure.

PMID- 24078478
TI  - Risk factors for the occurrence of spina bifida (a case-control study) and the
      prevalence rate of spina bifida in Japan.
AB  - BACKGROUND: The Japanese government recommended in 2000 that women planning
      pregnancy should take 400 MUg of folic acid daily to decrease the risk of having
      an infant with spina bifida. We aimed to identify risk factors for the occurrence
      of spina bifida and to evaluate how the prevalence rate has altered over the past
      3 decades. METHODS: Subjects comprised 360 women who gave birth to spina bifida
      affected offspring and 2333 women who gave birth to offspring without spina
      bifida between 2001 and 2012. A self-administered questionnaire was used to
      collect data, which were analyzed by multiple logistic regression models. The
      prevalence rate of spina bifida was obtained through data provided by
      international and domestic organizations. RESULTS: Four variables were
      significantly associated with the increased risk of having newborns afflicted
      with spina bifida: not taking folic acid supplements (odds ratios [OR], 2.50; 95%
      confidence interval [CI], 1.72-3.64), presence of spina bifida patients within
      third-degree relatives (OR, 4.26; 95% CI, 1.12-16.19), taking anti-epileptic
      drugs without folic acid (OR, 20.20; 95% CI, 2.06-198.17), and low birth weight
      in the newborns <= 2500 g (OR, 4.21; 95% CI, 3.18-5.59). The prevalence rate of
      spina bifida has remained 5 to 6 per 10,000 total births and has not shown any
      decreasing trend over the past 11 years. CONCLUSION: Four risk factors were
      identified among Japanese women. Because recommendations and information have not
      decreased the occurrence of spina bifida, the Japanese government should
      implement mandatory food fortification.

PMID- 24078479
TI  - [Counselling experts in rehabilitation].

PMID- 24078477
TI  - Neural tube defects, folate, and immune modulation.
AB  - Periconceptional supplementation with folic acid has led to a significant
      worldwide reduction in the incidence of neural tube defects (NTDs). However,
      despite increasing awareness of the benefits of folic acid supplementation and
      the implementation of food fortification programs in many countries, NTDs
      continue to be a leading cause of perinatal morbidity and mortality worldwide.
      Furthermore, there exists a significant subgroup of women who appear to be
      resistant to the protective effects of folic acid supplementation. The following
      review addresses emerging clinical and experimental evidence for a role of the
      immune system in the etiopathogenesis of NTDs, with the aim of developing novel
      preventative strategies to further reduce the incidence of NTD-affected
      pregnancies. In particular, recent studies demonstrating novel roles and
      interactions between innate immune factors such as the complement cascade,
      neurulation, and folate metabolism are explored.

PMID- 24078481
TI  - The horseshoe-shaped commissure of Wernekinck or the decussation of the brachium
      conjunctivum methodological changes in the 1840s.
AB  - Up till the 1840s, gross dissection was the only method available to study the
      tracts and fascicles of the white matter of the human brain. This changed
      dramatically with the introduction by Stilling (1842, 1843, 1846) of the
      microscopy of serial sections and his demonstration of the discriminative power
      of this method. The decussation of the brachium conjunctivum (the superior
      cerebellar peduncle) (International Anatomical Terminology (1998)) originally was
      known as the horseshoe-shaped commissure of Wernekinck. The first use of this
      name and the first illustrations of this commissure date from a book by
      Wernekinck's successor, Wilbrand (1840).Using gross dissection, he concluded that
      the commissure connects the dentate nucleus with the contralateral inferior
      olive. A few years later, Stilling (1846), using microscopy of serial sections
      through the human brain stem, illustrated the entire course of the brachium
      conjunctivum, its decussation,and its crossed ascending branch, up to the red
      nucleus. From his work, it became clear that Wernekinck and Wilbrand had included
      the central tegmental tract in their commissure, and that they had failed to
      identify its ascending branch.

PMID- 24078482
TI  - Transcranial direct current stimulation (tDCS) of the cortical motor areas in
      three cases of cerebellar ataxia.
AB  - The excitability of the motor areas of the cerebral cortex is reduced in ataxia.
      Since transcranial direct current stimulation (tDCS) is a noninvasive
      neuromodulation technique able to increase the cortical excitability, we assessed
      the effect of anodal tDCS over the motor cortex in three patients with ataxia. A
      clinical evaluation, a video-taped SARA rating scale and a gait analysis with
      cinematic parameters, were performed pre- and post-sham and anodal tDCS cycle.
      The full cycle was composed by five consecutive constant current sessions of
      stimulation. Anodal tDCS (2.0 mA, 20 min,max current density: 0.0278 mA/cm2, max
      total charge:0.033 C/cm2) was performed on the M1 area of the most affected side.
      The contralateral primary motor cortex underwent cathodal stimulation (2.0 mA, 20
      min, max current density:0.0278 mA/cm2, max total charge: 0.033 C/cm2). After
      anodal tDCS, gait analysis revealed an improvement of the symmetry of step
      execution and reduction of base-width lasting 30 days associated to patients'
      perception of amelioration. No relevant changes were found after sham
      stimulation. Our results suggest tDCS can improve gait symmetry in patients with
      ataxia for a short-term period. Future researches are needed in order to
      standardize time, amplitude, and area of stimulation in order to reach a long
      lasting effect on cerebellar ataxia.

PMID- 24078483
TI  - The growth of human scalp hair mediated by visible red light laser and LED
      sources in males.
AB  - BACKGROUND AND OBJECTIVES: Low level laser therapy (LLLT) has been used to
      promote hair growth. A double-blind randomized controlled trial was undertaken to
      define the safety and physiologic effects of LLLT on males with androgenic
      alopecia. METHODS: Forty-four males (18-48 yo, Fitzpatrick I-IV, Hamilton-Norwood
      IIa-V) were recruited. A transition zone scalp site was selected; hairs were
      trimmed to 3 mm height; the area was tattooed and photographed. The active group
      received a "TOPHAT655" unit containing 21, 5 mW lasers (655 +/- 5 nm), and 30
      LEDS (655 +/- 20 nm), in a bicycle-helmet like apparatus. The placebo group unit
      appeared identical, containing incandescent red lights. Patients treated at home
      every other day * 16 weeks (60 treatments, 67.3 J/cm(2) irradiance/25 minute
      treatment), with follow up and photography at 16 weeks. A masked 2.85 cm(2)
      photographic area was evaluated by another blinded investigator. The primary
      endpoint was the percent increase in hair counts from baseline. RESULTS: Forty
      one patients completed the study (22 active, 19 placebo). No adverse events or
      side effects were reported. Baseline hair counts were 162.7 +/- 95.9 (N = 22) in
      placebo and 142.0 +/- 73.0 (N = 22) and active groups respectively (P = 0.426).
      Post Treatment hair counts were 162.4 +/- 62.5 (N = 19) and 228.7 +/- 102.8 (N =
      22), respectively (P = 0.0161). A 39% percent hair increase was demonstrated
      (28.4 +/- 46.2 placebo, N = 19; 67.2 +/- 33.4, active, N = 22) (P = 0.001)
      Deleting one placebo group subject with a very high baseline count and a very
      large decrease, resulted in baseline hair counts of 151.1 +/- 81.0 (N = 21) and
      142.0 +/- 73.0 (N = 22), respectively (P = 0.680). Post treatment hair counts
      were 158.2 +/- 61.5 (N = 18) and 228.7 +/- 102.8 (N = 22) (P = 0.011), resulting
      in a 35% percent increase in hair growth (32.3 +/- 44.2, placebo, N = 18; 67.2 +/
      33.4, active, N = 22) (P = 0.003). CONCLUSIONS: LLLT of the scalp at 655 nm
      significantly improved hair counts in males with androgenetic alopecia.

PMID- 24078487
TI  - International Head and Neck Cancer Epidemiology Consortium: Update no. 12.

PMID- 24078485
TI  - Temporal trends in the incidence of osteoporotic fractures.
AB  - Osteoporotic fractures are associated with excess mortality and decreased
      functional capacity and quality of life. Age-standardized incidence rates of
      fragility fractures, particularly of the hip and forearm, have been noted to be
      decreasing in the last decade across many countries with the notable exception of
      Asia. The causes for the observed changes in fracture risk have not been fully
      identified but are likely the result of multiple factors, including birth cohort
      and period effects, increasing obesity, and greater use of anti-osteoporosis
      medications. Changing rates of fragility fractures would be expected to have an
      important impact on the burden of osteoporosis.

PMID- 24078486
TI  - Fluid responsiveness and brain tissue oxygen augmentation after subarachnoid
      hemorrhage.
AB  - BACKGROUND: The objective of this study was to investigate the relationship
      between cardiac index (CI) response to a fluid challenge and changes in brain
      tissue oxygen pressure (PbtO(2)) in patients with subarachnoid hemorrhage (SAH).
      METHODS: Prospective observational study was conducted in a neurological
      intensive care unit of a university hospital. Fifty-seven fluid challenges were
      administered to ten consecutive comatose SAH patients that underwent
      multimodality monitoring of CI, intracranial pressure (ICP), and PbtO(2),
      according to a standardized fluid management protocol. RESULTS: The relationship
      between CI and PbtO(2) was analyzed with logistic regression utilizing
      generalized estimating equations. Of the 57 fluid boluses analyzed, 27 (47 %)
      resulted in a >= 10 % increase in CI. Median absolute (+5.8 vs. +1.3 mmHg) and
      percent (20.7 vs. 3.5 %) changes in PbtO(2) were greater in CI responders than in
      non-responders within 30 min after the end of the fluid bolus infusion. In a
      multivariable model, a CI response was independently associated with PbtO(2)
      response (adjusted odds ratio 21.5, 95 % CI 1.4-324, P = 0.03) after adjusting
      for mean arterial pressure change and end-tidal CO(2). Stroke volume variation
      showed a good ability to predict CI and PbtO(2) response with areas under the ROC
      curve of 0.86 and 0.81 with the best cut-off values of 9 % for both responses.
      CONCLUSION: Bolus fluid resuscitation resulting in augmentation of CI can improve
      cerebral oxygenation after SAH.

PMID- 24078488
TI  - Keeping the 'Goose' on the Menu: Response to Commentaries on Financial Incentives
      in Health Behaviour Change.
AB  - We welcome the commentaries by Hagger et al. and Stephens and consider their
      observations to be timely and constructive. Hagger et al. raise concerns
      regarding the sustainability of behaviour change once incentives have been
      removed and their influence on intrinsic motivation.We concur that questions
      regarding both of these issues remain but argue that, in the case of
      sustainability, there is some evidence to support long-term behaviour change,
      given particular conditions. Given that the question of maintenance is applicable
      to any health intervention, we propose that the role of incentives may be better
      matched with motivating initial behaviour change, and researchers should explore
      other mechanisms for sustaining behaviour change and intrinsic motivation, over a
      longer period of time.Stephens highlights the complexity of health behaviours and
      warns of the dangers associated with taking an individualised approach to health
      promotion.We support the need for both downstream and upstream approaches to
      reducing health inequalities and contend that financial incentives still have a
      potential role to play in encouraging health behaviour change.

PMID- 24078490
TI  - Reported exposures to anti-smoking messages and their impact on Chinese smoker's
      subsequent quit attempts.
AB  - BACKGROUND: It is important to monitor whether anti-smoking messages (if any) are
      noticed by the public in China and whether they have any impact on smokers'
      quitting behaviours over time. PURPOSE: This study aimed to examine Chinese
      smokers' exposure to anti-smoking messages in a range of channels and to
      determine if exposure was associated with subsequent quit attempts. METHOD: A
      prospective cohort design was employed. Participants were 6,509 adult smokers who
      completed at least one of the first three waves (2006-2009) of the International
      Tobacco Control (ITC) China Survey sampled from six Chinese cities. The main
      measures were reported exposure to anti-smoking messages in a range of channels
      and smokers' subsequent quit attempts. Generalized Estimating Equations (GEE)
      modelling was used to combine respondents from all three waves while accounting
      for inherent within-person correlation. RESULTS: The overall exposure levels to
      anti-smoking messages were low and varied between cities and from one channel to
      another. Television was the medium with the greatest overall exposure (over 50%
      in almost all the cities across all the waves). After controlling for a range of
      covariates, higher level of combined exposure were positively related to higher
      subsequent quit attempts (adjusted odds ratio=1.03, 95% CI 1.02~1.05, p <.001);
      among the individual channels, exposures in newspapers and on posters were
      significant in their own right. CONCLUSION: The findings suggest that anti
      smoking warning messages have the potential to stimulate Chinese smokers to make
      quit attempts, but they also indicate that the levels and strength of warning
      messages in China need to be increased. China should consider adopting proven
      international practices, including mandating pictorial health warnings on
      cigarette packages, adopting prominent point-of-sale warnings, and carrying out
      strong and ongoing mass media campaigns.

PMID- 24078493
TI  - Lessons from developmental biology for regenerative medicine.
AB  - The ultimate goal of regenerative medicine is the functional restoration of lost
      or damaged tissues and organs. Since most tissues in man lack true regenerative
      properties and instead respond to injury with an inflammatory response and scar
      tissue formation, regenerative medicine strategies that include combinations of
      cells, scaffolds, and bioactive molecules to replace injured or missing tissues
      have been developed. The physical, chemical, and electrical cues that define the
      microenvironmental niche and the effect of these influences upon cell behavior
      during development are of interest to developmental biologists, with obvious
      overlap to the interest of the regenerative medicine field. This manuscript
      provides an overview of current approaches for tissue restoration being
      investigated in the field of regenerative medicine and attempts to identify areas
      of mutual beneficial interest with the field of developmental biology.

PMID- 24078491
TI  - The effects of tai chi on depression, anxiety, and psychological well-being: a
      systematic review and meta-analysis.
AB  - BACKGROUND: Tai chi, also called taiji or tai chi chuan, is a form of mind-body
      exercise that originated from China. It combines Chinese martial arts and
      meditative movements that promote balance and healing of the mind and body,
      involving a series of slowly performed, dance-like postures that flow into one
      another. As it comprises mental concentration, physical balance, muscle
      relaxation, and relaxed breathing, tai chi shows great potential for becoming
      widely integrated into the prevention and rehabilitation of a number of medical
      and psychological conditions. PURPOSE: A growing body of clinical research has
      begun to evaluate the efficacy of tai chi as a therapy for a variety of health
      issues. A systematic review and meta-analysis were carried out on randomized
      controlled trials (RCTs) and quasi-experimental (Q-E) trials that studied the
      effects of tai chi on psychological well-being. METHOD: Drawn from English and
      Chinese databases, 37 RCTs and 5 Q-E studies published up to May 31, 2013 were
      included in the systematic review. The methodological quality of the RCTs was
      evaluated based on the following criteria: adequate sequence generation,
      allocation concealment, blinding, completeness of outcome data, selective
      reporting, and other potential biases. Statistical analyses were performed using
      Review Manager version 5.0. RESULTS: The studies in this review demonstrated that
      tai chi interventions have beneficial effects for various populations on a range
      of psychological well-being measures, including depression, anxiety, general
      stress management, and exercise self-efficacy. Meta-analysis was performed on
      three RCTs that used depression as an outcome measure (ES=-5.97; 95% CI -7.06 to 
      4.87), with I2=0%. CONCLUSION: In spite of the positive outcomes, the studies to
      date generally had significant methodological limitations. More RCTs with
      rigorous research design are needed to establish the efficacy of tai chi in
      improving psychological well-being and its potential to be used in interventions
      for populations with various clinical conditions.

PMID- 24078494
TI  - Recent advances in heart regeneration.
AB  - Although cardiac stem cells (CSCs) and tissue engineering are very promising for
      cardiac regenerative medicine, studies with model organisms for heart
      regeneration will provide alternative therapeutic targets and opportunities.
      Here, we present a review on heart regeneration, with a particular focus on the
      most recent work in mouse and zebrafish. We attempt to summarize the recent
      progresses and bottlenecks of CSCs and tissue engineering for heart regeneration;
      and emphasize what we have learned from mouse and zebrafish regenerative models
      on discovering crucial genetic and epigenetic factors for stimulating heart
      regeneration; and speculate the potential application of these regenerative
      factors for heart failure. A brief perspective highlights several important and
      promising research directions in this exciting field.

PMID- 24078495
TI  - Osteoblast recruitment to sites of bone formation in skeletal development,
      homeostasis, and regeneration.
AB  - During endochondral bone development, bone-forming osteoblasts have to colonize
      the regions of cartilage that will be replaced by bone. In adulthood, bone
      remodeling and repair require osteogenic cells to reach the sites that need to be
      rebuilt, as a prerequisite for skeletal health. A failure of osteoblasts to reach
      the sites in need of bone formation may contribute to impaired fracture repair.
      Conversely, stimulation of osteogenic cell recruitment may be a promising osteo
      anabolic strategy to improve bone formation in low bone mass disorders such as
      osteoporosis and in bone regeneration applications. Yet, still relatively little
      is known about the cellular and molecular mechanisms controlling osteogenic cell
      recruitment to sites of bone formation. In vitro, several secreted growth factors
      have been shown to induce osteogenic cell migration. Recent studies have started
      to shed light on the role of such chemotactic signals in the regulation of
      osteoblast recruitment during bone remodeling. Moreover, trafficking of
      osteogenic cells during endochondral bone development and repair was visualized
      in vivo by lineage tracing, revealing that the capacity of osteoblast lineage
      cells to move into new bone centers is largely confined to undifferentiated
      osteoprogenitors, and coupled to angiogenic invasion of the bone-modeling
      cartilage intermediate. It is well known that the presence of blood vessels is
      absolutely required for bone formation, and that a close spatial and temporal
      relationship exists between osteogenesis and angiogenesis. Studies using
      genetically modified mouse models have identified some of the molecular
      constituents of this osteogenic-angiogenic coupling. This article reviews the
      current knowledge on the process of osteoblast lineage cell recruitment to sites
      of active bone formation in skeletal development, remodeling, and repair,
      considering the role of chemo-attractants for osteogenic cells and the interplay
      between osteogenesis and angiogenesis in the control of bone formation.

PMID- 24078496
TI  - Toward regeneration of articular cartilage.
AB  - Articular cartilage is classified as permanent hyaline cartilage and has
      significant differences in structure, extracelluar matrix components, gene
      expression profile, and mechanical property from transient hyaline cartilage
      found in the epiphyseal growth plate. In the process of synovial joint
      development, articular cartilage originates from the interzone, developing at the
      edge of the cartilaginous anlagen, and establishes zonal structure over time and
      supports smooth movement of the synovial joint through life. The cascade actions
      of key regulators, such as Wnts, GDF5, Erg, and PTHLH, coordinate sequential
      steps of articular cartilage formation. Articular chondrocytes are restrictedly
      controlled not to differentiate into a hypertrophic stage by autocrine and
      paracrine factors and extracellular matrix microenvironment, but retain potential
      to undergo hypertrophy. The basal calcified zone of articular cartilage is
      connected with subchondral bone, but not invaded by blood vessels nor replaced by
      bone, which is highly contrasted with the growth plate. Articular cartilage has
      limited regenerative capacity, but likely possesses and potentially uses
      intrinsic stem cell source in the superficial layer, Ranvier's groove, the intra
      articular tissues such as synovium and fat pad, and marrow below the subchondral
      bone. Considering the biological views on articular cartilage, several important
      points are raised for regeneration of articular cartilage. We should evaluate the
      nature of regenerated cartilage as permanent hyaline cartilage and not just
      hyaline cartilage. We should study how a hypertrophic phenotype of transplanted
      cells can be lastingly suppressed in regenerating tissue. Furthermore, we should
      develop the methods and reagents to activate recruitment of intrinsic
      stem/progenitor cells into the damaged site.

PMID- 24078498
TI  - Mirabegron for overactive bladder: a novel, first-in-class beta3-agonist therapy.
AB  - PURPOSE: To discuss the pharmacotherapeutic aspects of Mirabegron which is a
      first-in class novel beta3 receptor agonist drug recently approved by the food
      and drug administration (FDA) for the treatment of overactive bladder (OAB).
      MATERIALS AND METHODS: We conducted a computerized search of the MEDLINE/PUBMED
      databases with the word Mirabegron, beta3 receptor agonist and overactive
      bladder. RESULTS: Effect of Mirabegron on beta3 adrenergic receptor purportedly
      releases nitric oxide(NO) by an increase in intracellular Ca2+ through
      accumulation of cyclic adenosine monophosphate (cAMP). Along with NO which
      relaxes the detrusor muscle, it also releases an urothelial-derived inhibiting
      factor (UDIF) that inhibits contractions. It increases the bladder capacity by
      causing bladder relaxation during the storage phase. CONCLUSION: Mirabegron
      appears to be a promising treatment in OAB patients by shifting its management
      from reducing detrusor over-activity to inducing relaxation. Also it lacks the
      troublesome side effects associated with the standard antimuscarinic management.

PMID- 24078499
TI  - Transurethral extrusion of penile prosthesis.

PMID- 24078500
TI  - Comparative study between three analgesic agents for the pain management during
      extracorporeal shock wave lithotripsy.
AB  - PURPOSE: To compare the clinical efficacy between locally applied diclofenac
      diethylamine gel, EMLA cream and systemically given diclofenac sodium for the
      pain relief during extracorporeal shock wave lithotripsy (SWL) using Dornier
      Delta Compact Lithotripter. MATERIAL AND METHODS: One hundred five patients with
      renal stones were randomly divided in to 3 groups. Group A was given
      intramuscular diclofenac sodium (1 mg/kg), 45 minutes before the procedure. In
      group B, 10 gm of eutectic mixture of local anesthetic (EMLA) cream and in group
      C, 15 gm of diclofenac diethylamine gel was applied locally 45 minutes before the
      procedure. Ten-score linear and visual analogue scale (VAS) was used to assess
      the severity of pain during the procedure. Analysis of variance (ANOVA) test was
      used to compare various parameters and analyzed statistically. RESULTS: All the
      three groups were not statistically different with respect to age, weight, stone
      size, number of shock wave delivered and maximum voltage used (P > .05). The mean
      pain score in group A was 4.48, in group B was 3.60 and in group C was 3.95,
      which were not significantly different (P = 1.34). Complication like skin lesion
      was found only in injection diclofenac sodium group whereas cold sensation at the
      local site was typically found in diclofenac diethylamine gel group. CONCLUSION:
      Although not statistically significant, the mean pain score in locally applied
      analgesic agents (EMLA and diclofenac diethylamine gel) is lower as compared to
      intramuscularly given diclofenac sodium. Among these two locally acting drugs,
      diclofenac diethylamine gel is an equally effective alternative to EMLA.

PMID- 24078501
TI  - Anti-urolithiatic effect of ethanolic extract of Pedalium murex linn. fruits on
      ethylene glycol-induced renal calculi.
AB  - PURPOSE: To evaluate effect of ethanolic extract of Pedalium murex Linn. fruits
      on experimental model of calcium oxalate nephrolithiasis. MATERIALS AND METHODS:
      Thirty-six male Wistar albino rats were randomly divided in 6 groups.Normal
      controls received distilled water for 28 days. Other five groups received
      ethylene glycol(1% v/v) in distilled water for 28 days. Pedalium murex ethanolic
      extract was given 200 mg/kg and 400 mg/kg orally in distilled water for 28 days
      in prophylactic groups (III and IV) and from 15th to 28th days in treatment
      groups (V and VI). The urea, creatinine, random blood sugar, aspartate
      aminotransferase, alanine aminotransferase, alkaline phosphatase, bilirubin and
      calcium were measured on 28th day. 24 hr urinary oxalate and volume were measured
      on day 0 and 28. On day 28, kidneys were removed, weighed and subjected to
      histopathological examination. Calcium oxalate crystallization was evaluated by
      renal histopathology and in-vitro method of mineralization.All parameters were
      analyzed by Kruskal-Wallis or one-way ANOVA with post-hoc test. RESULTS: Pedalium
      murex showed significant improvement in renal function and kidney weight
      inprophylactic groups as compared to ethylene glycol controls. It did not show
      any effect on urinary oxalate, urine volume and any other serological parameters.
      Calcium oxalate crystallization was significantly reduced in all the Pedalium
      murex treated groups (P < .05). Calcium oxalate and phosphate mineralization were
      also inhibited by 33% and 57%. CONCLUSION: Ethanolic extract of Pedalium murex
      fruits possess significant activity for prevention of renal calculi.

PMID- 24078502
TI  - Long-term effects of elevated intra-abdominal pressure on testes an experimental
      model of laparoscopy.
AB  - PURPOSE: To determine the long-term outcomes of pneumoperitoneum on the testes in
      an experimental laparoscopy model. MATERIALS AND METHODS: Twenty-four rats were
      divided into three groups: Group A, the control group; Group B, exposed to a 10
      mmHg intra-abdominal pressure (IAP); and Group C, exposed to a 20 mmHg IAP with
      CO2 pneumoperitoneum for 60 minutes. After 6 weeks, the testes were removed, and
      testicular injury score and Johnson score were examined histologically. Germ cell
      apoptosis was also detected using flow cytometry. RESULTS: A significant
      difference was determined between all groups in terms of testicular injury
      scores, Johnson scores, and germ cell apoptosis percentages. For the testicular
      injury score, there were significant differences between the groups for the right
      testis (group A versus B, P = .009; group A versus C, P < .0001; and group B
      versus C, P = .001) and for the left testis (group A versus B, P = .001; group A
      versus C, P < .0001; and group B versus C, P = .002). Significant differences
      were determined in the Johnson scores for the right testis between all groups
      (group A versus B, P= .001; group A versus C, P < .0001; and group B versus C, P
      = .008, respectively). Percentage of apoptotic testis cells were significantly
      differed between all groups (P = .001 for each). CONCLUSION: This study shows
      that increased IAP during pneumoperitoneum causes histopathology and
      apoptotically-evident damage to the testes in the long-term, depending on the
      magnitude of IAP increase, which may cause sub/infertility. Considering the
      experimental nature of this study,further clinical studies are needed for a more
      decisive conclusion.

PMID- 24078497
TI  - Tendon and ligament regeneration and repair: clinical relevance and developmental
      paradigm.
AB  - As dense connective tissues connecting bone to muscle and bone to bone,
      respectively, tendon and ligament (T/L) arise from the somitic mesoderm,
      originating in a recently discovered somitic compartment, the syndetome.
      Inductive signals from the adjacent sclerotome and myotome upregulate expression
      of Scleraxis, a key transcription factor for tenogenic and ligamentogenic
      differentiation. Understanding T/L development is critical to establishing a
      knowledge base for improving the healing and repair of T/L injuries, a high
      burden disease due to the intrinsically poor natural healing response. Current
      treatment of the three most common tendon injuries-tearing of the rotator cuff of
      the shoulder, flexor tendon of the hand, and Achilles tendon-include mostly
      surgical repair and/or conservative approaches, including biophysical modalities
      such as rehabilitation and cryotherapy. Unfortunately, the fibrovascular scar
      formed during healing possesses inferior mechanical and biochemical properties,
      resulting in compromised tissue functionality. Regenerative approaches have
      sought to augment the injured tissue with cells, scaffolds, bioactive agents, and
      mechanical stimulation to improve the natural healing response. The key
      challenges in restoring full T/L function following injury include optimal
      combination of these biological agents as well as their delivery to the injury
      site. A greater understanding of the molecular mechanisms involved in T/L
      development and natural healing, coupled with the capability of producing complex
      biomaterials to deliver multiple biofactors with high spatiotemporal resolution
      and specificity, should lead to regenerative procedures that more closely
      recapitulate T/L morphogenesis, thereby offering future patients the prospect of
      T/L regeneration, as opposed to simple tissue repair.

PMID- 24078503
TI  - Cytosolic HMGB1 expression in human renal clear cell cancer indicates higher
      pathological T classifications and tumor grades.
AB  - PURPOSE: High mobility group box (HMGB) proteins are nuclear nonhistone
      chromosomal proteins that bend DNA, bind preferentially to distorted DNA
      structures, and promote the assembly of site-specific DNA binding proteins.
      Recent reports indicate that HMGB1 functions as a proinflammatory cytokine. Here,
      we studied expressions of HMGB1 and HMGB2 in human renal cancer. MATERIAL AND
      METHODS: Immunohistological expressions of HMGB1 and HMGB2 were assessed in 39
      surgically resected human renal cancer specimens. RESULTS: HMGB1 was expressed in
      the nucleus in 37 out of 39 (94.9%) renal clear cell cancers,while its expression
      in the cytosol was noted in 19 cases (48.7%). Cytosolic HMGB1 is expressed more
      frequently in cancers beyond the pT1b classification than in those at the pT1a
      classification. Higher tumor grades (>= G2) were also significantly linked with
      the cytosolic expression of HMGB1. HMGB2 was expressed in the nucleus in 35 of 39
      (89.7%) renal clear cell cancers, while its expression in the cytosol was
      observed in only 7 case (17.9%). Linkage between cytosolic expression of HMGB2
      and T classifications was weakly observed, while that between nuclear expression
      and T classifications was not. CONCLUSION: HMGB1 expressed in the cytoplasm may
      be an effective marker indicating higher T classifications and tumor grades.

PMID- 24078504
TI  - Bilateral cancer in prostate biopsy associates with the presence of extracapsular
      disease and positive surgical margins in low risk patients: a consideration for
      bilateral nerve sparing radical prostatectomy decision.
AB  - PURPOSE: To evaluate the epidemiological, clinical and pathological parameters
      that may predict the presence of positive surgical margins and extraprostatic
      disease in patients with low risk [prostate specific antigen (PSA) < 10, and
      Gleason score <= 6, stage T1c)] prostate cancer. MATERIALS AND METHODS: We
      retrospectively analyzed the medical records of patients who had undergone
      radical prostatectomy from January 2005 until January 2011. The analysis
      comprised patients age, preoperative serum prostate specific antigen (PSA) level,
      prostate volume, PSA density, biopsy Gleason score, the presence of bilateral
      disease according to the results of biopsy cores analysis, the percentage of
      cancer in biopsy material and the presence of high grade prostatic
      intraepithelial neoplasia. RESULTS: A total of 117 patients were included in the
      study. Positive surgical margins were found in 37 (31.6%) patients and 23 (19.7%)
      had advanced disease. The results of the multivariate analysis showed that
      bilateral disease was the single significant predictor for advanced disease
      prediction (P = .04). Same results was obtained by the univariate analysis of the
      variables for prediction of positive surgical margins, where bilateral disease
      after biopsy cores analysis was the only factor to be statistical significant (P
      = .018). CONCLUSION: Bilateral prostate cancer in prostate biopsy is
      significantly associated with positive surgical margins and advanced disease in
      patients that are operated for prostate cancer of low risk.This observation may
      assist the selection of patients in whom a bilateral nerve sparing radical
      prostatectomy is planned to be performed.

PMID- 24078505
TI  - The impact of unilateral experimental rat varicocele model on testicular
      histopathology, Leydig cell counts, and intratesticular testosterone levels of
      both testes.
AB  - PURPOSE: Varicocele, most treatable pathologic condition in male infertility,
      exerts unfavorable effects on testicular ultrastructure via various mechanisms.
      In this study we aimed to demonstrate adverse effects of varicocele on both
      testes. MATERIALS AND METHODS: Twenty one adult male Albino rats were divided
      into 3 groups. Sham operation was performed for group 1 (control group), and this
      group of rats were sacrificed 4 weeks later. Experimental varicocele model was
      performed for group 2 (varicocele group) and these animals were sacrificed 4
      weeks after the operation. In group 3 the rats were varicocelectomized 4 weeks
      later. This group of rats were sacrificed at 4 weeks postoperatively. The level
      of testicular damage was examined, and serum testosterone and intratesticular
      testosterone levels were measured. RESULTS: Mean (+/-SD) damage scores of the
      right testes of the sham, varicocele, and varicocelectomy groups were 0, 1.64 +/-
      1.3, and 1.21 +/- 0.3, respectively. There was no statistically significant
      differences between damage scores of groups 2, and 3 (P = .320), relevant scores
      of both groups were determined to be significantly higher than group 1 (P = .009,
      and P = .001). Mean (+/-) damage scores of the left testes of the three groups
      were detected to be 0.43 +/- 1.13, 2.29 +/- 1.15, and 1.78 +/- 0.39,
      respectively. The difference between varicocele, and varicocelectomy groups was
      not statistically significant (P = .112). CONCLUSION: Unilateral varicocele has
      deleterious effects on both testes. There was no statistically significant
      difference as for histopathologic recovery following varicocelectomy.

PMID- 24078506
TI  - Co-regulated expression of TGF-beta Variants and miR-21 in bladder cancer.
AB  - PURPOSE: To investigate a potential alteration in the expression levels of
      transforming growth factor beta (TGF-beta) and miR-21 in bladder cancer tissues.
      MATERIAL AND METHODS: Using real-time polymerase chain reaction (PCR) method, we
      examined a potential correlated expression of miR-21 and TGF-beta variants in 30
      bladder tumors and their marginal/non-tumor biopsy specimens obtained from the
      same patients. RESULTS: Our data revealed a significant down-regulation of TGF
      beta variants (P = .03) along with a non-significant alteration in the expression
      of miR-21 in tumor vs. non-tumor samples. However, in contrast to low-grade
      tumors, the expression of miR-21 was upregulated in high-grade ones, and the
      expression level can efficiently discriminate low-grade tumors from high-grade
      ones (P = .03). CONCLUSION: In accordance to the observed similarity between TGF
      beta variants and miR-21 gene expression alterations in bladder tumors, treating
      5637 bladder cancer cell line with TGF-beta recombinant protein caused a
      significant upregulation of miR-21. The later finding further confirmed a
      correlated expression of TGF-beta and miR-21 in bladder tumors.

PMID- 24078507
TI  - Unwanted intra-operative penile erection during pediatric hypospadiasis repair.
      Comparison of propofol and halothane.
AB  - PURPOSE: To compare the erectile effect of propofol and halothane on unwanted
      intraoperative penile erection (UIOPE) during pediatric hypospadiasis repair.
      MATERIALS AND METHODS: One hundred and seventeen boys who were in the age range
      of 6 months to 6 years and referred for hypospadiasis repair to our referral
      teaching hospital were included in this randomized clinical trial. Patients were
      randomly assigned to one of the two study groups before anesthesia induction.
      Anesthesia was maintained with a continuous intravenous infusion of propofol and
      inhalational halothane in the propofol (P) and halothane (H) groups,
      respectively. Data regarding the patients' age, weight, pre- and intra-operative
      chordee, UIOPE, anesthesia time, surgery time, hematoma formation, and wound
      infection were collected. The Chi-Square and Fisher's exact tests were used for
      comparison. RESULTS: No statistically significant differences were noted
      regarding age, weight, and pre and intra-operative chordee between the two
      groups. The incidence of UIOPE (10.34% versus 57.63%; P = .000), anesthesia time
      (174.15 +/- 15.02 versus 181.26 +/- 15.19; P =.012), and surgery time (162.34 +/-
      12.99 versus 167.69 +/- 13.90 +/- 13.90; P = .034) were significantly lower in
      group P compared with group H. CONCLUSION: The use of propofol during
      hypospadiasis surgical repair is more safe and effective than halothane in
      preventing UIOPE and reducing surgery and anesthesia time.

PMID- 24078508
TI  - Comparing the effectiveness of intranasal desmopressin and doxazosin in men with
      nocturia: a pilot randomized clinical trial.
AB  - PURPOSE: We aimed to compare the effectiveness of intranasal desmopressin and
      doxazosin treatments in patients with nocturia and benign prostatic hyperplasia
      (BPH). MATERIAL AND METHODS: Thirty one men with BPH and three or more episodes
      of nocturia were randomized to receive 2 mg doxazosin at night for two weeks
      increasing to 4 mg for a further two weeks versus 20 MUg intranasal desmopressin
      at night. For all patients, number of nocturia, urinary flow rate, residual urine
      volume and quality of life score were checked. Outcomes were measured at two
      months. The comparison of before and after treatment changes between the groups
      were done by student's t-test. RESULTS: In doxazosin group, mean number of
      nocturia were 3.2 &plus mn; 0.4 (3-4 times) times per night and 1.2 +/- 0.8 (0-3
      times) times per night before and after treatment, respectively. In desmopressin
      group, mean number of nocturia were 3.4 +/- 0.5 (3-4 times) and 1.5 +/- 0.6 (1-3
      times) times per night before and after treatment, respectively. In doxazosin
      group, mean residual urine volumes were 44.3 +/- 35.9 ml (range 0-120 ml) and
      23.1 +/- 18.8 ml (range 0-50 ml) before and after treatment, respectively. In
      desmopressin group, mean residual urine volumes were 36.6 +/- 32.4 ml (range 0
      120 ml) and 14.0 +/- 26.9 ml (range 0-90 ml) before and after treatment,
      respectively. Improvements in number of nocturia, residual urine volume, quality
      of life scores and peak urinary flow rates weren't statistically significant
      between two groups, whereas change in international prostate symptom score (IPSS)
      score was more significant in doxazosin group. CONCLUSION: Intranasal
      desmopressin, is an effective symptomatic treatment of men with BPH complaining
      of nocturia, as well as doxazosin treatment.

PMID- 24078510
TI  - Primary hydatid cyst of the kidney in a 10 year old boy.

PMID- 24078509
TI  - Autologous fibrin sealant in tubeless percutaneous nephrolithotomy; a prospective
      study.
AB  - PURPOSE: To evaluate the efficacy of autologous single-donor fibrin glue after
      tubeless percutaneous nephrolithotomy (PCNL). MATERIALS AND METHODS: Forty-three
      patients were planned for tubeless PCNL in a prospective cohort study and
      randomized in two groups with or without using fibrin glue. Randomization method
      was based on the computer-generated random numbers. RESULTS: Transfusion, urinary
      leakage, or major complications were found in neither of the groups. There was no
      difference between two groups in stone free rate (P = .53), and changes in
      hemoglobin (P = .61) and serum creatinine (P = .63) level. CONCLUSION: Although
      autologous fibrin glue did not play any significant role in improving results or
      decreasing complications after tubeless PCNL in our study, its use was safe and
      did not increase complications.

PMID- 24078511
TI  - Laparoscopy assisted 'U' configuration bilateral ileal ureter in pelvic
      lipomatosis with bilateral ureteric obstruction.

PMID- 24078512
TI  - Lower moiety pelvi ureteric junction obstruction leading to acute renal failure
      in an ectopic fused kidney.

PMID- 24078513
TI  - Emergency laparoscopic orchiectomy for intra-abdominal testicular torsion--a case
      report.

PMID- 24078514
TI  - Prostate cancer screening: yes or no?

PMID- 24078515
TI  - Predictors of endothelial dysfunction in patients with rheumatoid arthritis.
AB  - We investigated the predictors of endothelial dysfunction in patients with
      rheumatoid arthritis (RA) by brachial artery flow-mediated vasodilatation (FMD).
      The study population included 50 patients with RA and 30 controls. Disease
      activity score (DAS28) was calculated for patients with RA. An FMD response <7%
      was accepted as impaired FMD. Brachial artery Doppler study revealed that in
      patients with RA, FMD% was significantly lower as compared with controls (6.6% +/
      3.5% vs 9.7% +/- 41%, P = .002). After multivariate logistic regression
      analysis, erythrocyte sedimentation rate (ESR; OR: 1.086, 95% confidence interval
      [CI]: 1.012-1.167, P = .023), duration of RA (OR: 1.392, 95% CI: 1.044-1.856, P =
      .024), and DAS28 (OR: 3.335, 95% CI: 1.067-10.42, P = .038) were independent
      predictors of impaired FMD in patients with RA. Endothelial function is impaired
      in patients with RA. Disease duration, DAS28, and ESR indicating active
      inflammation are independent predictors of impaired FMD in patients with RA. 

PMID- 24078516
TI  - Increased aortic stiffness predicts contrast-induced nephropathy in patients with
      stable coronary artery disease undergoing percutaneous coronary intervention.
AB  - Increased aortic stiffness (AS) has been shown to be an independent risk factor
      for cardiovascular disease in renal failure and was also found to be associated
      with even mild renal insufficiency. We investigated the relationship between
      contrast-induced nephropathy (CIN) and AS parameters such as pulse wave velocity
      (PWV) and augmentation index (AIx). Patients (n = 440) with stable coronary
      artery disease (CAD) treated with percutaneous coronary intervention (PCI) were
      included prospectively (mean age: 60.3 +/- 10.3 years). The PWV and AIx were
      calculated using the single-point method. The PWV, age, diabetes, SYNTAX score,
      and contrast media dose were independent predictors for CIN (P < .05, for all).
      The cutoff value for PWV obtained by the receiver-operator characteristic curve
      analysis was 10.35 m/s for the prediction of CIN (95% confidence interval: 0.838
      0.916, sensitivity: 82.1%, specificity: 77.9%, and P < .001). In conclusion, a
      greater AS pre-PCI may predict CIN development in patients with stable CAD. 

PMID- 24078517
TI  - Combined coronary artery bypass grafting and open abdominal aortic aneurysm
      repair is a reasonable treatment approach: a systematic review.
AB  - We reviewed the literature for studies investigating the outcomes of combined 1
      stage coronary artery bypass grafting (CABG) and abdominal aortic aneurysm (AAA)
      open repair (OR) procedures. An electronic search of the English literature was
      conducted using the PubMed, EMBASE, and Cochrane databases. Age, coronary heart
      disease severity, AAA size, mean duration from CABG to AAA OR procedures, details
      of each procedure, mortality, and morbidity rates were analyzed. Between 1994 and
      2012, 12 studies (256 patients) with 1-stage treatment fulfilled the inclusion
      criteria and were analyzed. There were 20 early (30 days) deaths, accounting for
      a 30-day mortality rate of 7.8%. The early morbidity was 53% (136 of 256). One
      stage treatment when necessary can be undertaken with acceptable mortality and
      reasonable morbidity rates considering the complexity of both the operations.
      Nowadays, endovascular AAA repair is preferred over OR. The outcomes of combined
      cardiac surgery and endovascular AAA repair have not been extensively evaluated. 

PMID- 24078519
TI  - Site-dependent differences in density of sympathetic nerve fibers in muscle
      innervating nerves of the human head and neck.
AB  - The autonomic nerve supply of skeletal muscle has become a focus of interest
      because it is closely related to the adaptation of energy metabolism with aging.
      We have performed an immunohistochemistry study on tyrosine hydroxylase (TH) and
      neuronal nitric oxide synthase (nNOS) using specimens obtained from ten selected
      elderly cadavers (mean age 83.3 years) in which we examined muscle-innervating
      nerves (abbreviated ''muscle-nerves'' hereafter) of ten striated muscles (soleus,
      infraspinatus, extra-ocular inferior rectus, lateral rectus, superior obliquus,
      temporalis, orbicularis oculi, posterior cricoarytenoideus, trapezius and
      genioglossus) and, as a positive control, the submandibular ganglion. We found
      that the extra-ocular muscles received no or very few TH-positive nerve fibers.
      Muscle-nerves to the other head and neck muscles contained a few or several TH
      positive fibers per section, but their density (proportional area of TH-positive
      fibers per nerve cross-section) was one-half to one-third of that in nerves to
      the soleus or infraspinatus. We did not find nNOS-positive fibers in any of these
      muscle-nerves. In the head and neck muscles, with the exception of those of the
      tongue, there appeared to be very few TH-positive nerve fibers along the feeding
      artery. Consequently, the head and neck muscles seemed to receive much fewer
      sympathetic nerves than limb muscles. There was no evidence that nNOS-positive
      nerves contributed to vasodilation of feeding arteries in striated muscles. This
      site-dependent difference in sympathetic innervation would reflect its commitment
      to muscle activity. However, we did not find any rules determining the density of
      nerves according to muscle fiber type and the mode of muscle activity.

PMID- 24078518
TI  - Reference genes in real-time PCR.
AB  - This paper aims to discuss various aspects of the use of reference genes in qPCR
      technique used in the thousands of present studies. Most frequently, these are
      housekeeping genes and they must meet several criteria so that they can lay claim
      to the name. Lots of papers report that in different conditions, for different
      organisms and even tissues the basic assumption-the constant level of the
      expression is not maintained for many genes that seem to be perfect candidates.
      Moreover, their transcription can not be affected by experimental factors. Sounds
      simple and clear but a great number of designed protocols and lack of consistency
      among them brings confusion on how to perform experiment properly. Since during
      selection of the most stable normalizing gene we can not use any reference gene,
      different ways and algorithms for their selection were developed. Such methods,
      including examples of best normalizing genes in some specific cases and possible
      mistakes are presented based on available sources. Numerous examples of reference
      genes applications, which are usually in too few numbers in relevant articles not
      allowing to make a solid fundament for a reader, will be shown along with
      instructive compilations to make an evidence for presented statements and an
      arrangement of future qPCR experiments. To include all the pitfalls and problems
      associated with the normalization methods there is no way not to begin from
      sample preparation and its storage going through candidate gene selection, primer
      design and statistical analysis. This is important because numerous short reviews
      available cover the topic only in lesser extent at the same time giving the
      reader false conviction of complete topic recognition.

PMID- 24078520
TI  - Mechanisms of anti-inflammatory property of conserved dopamine neurotrophic
      factor: inhibition of JNK signaling in lipopolysaccharide-induced microglia.
AB  - Microglia are important resident immune cells in the central nervous system (CNS)
      and involved in the neuroinflammation caused by CNS disorders, including brain
      trauma, ischemia, stroke, infections, inflammation, and neurodegenerative
      diseases. Our study explores the hypothesis that conserved dopamine neurotrophic
      factor (CDNF), a secretory neurotrophic factor, may provide a novel therapy for
      associated with neuroinflammation related to the microglia. We observed that CDNF
      was upregulated in rat primary microglia treated with 1 MUg/mL
      lipopolysaccharide, an inflammatory inducer, for 24 h. Thus, we hypothesize that
      CDNF may play a role, mediator or inhibitor, in regulating the inflammation in
      microglial cells induced by LPS. Finally, our data showed that CDNF significantly
      attenuated the production of proinflammatory cytokines (PGE2 and IL-1beta) and
      remarkably alleviated the cytotoxicity (percentage of lactate dehydrogenase
      released) in the LPS-induced microglia by suppressing the phosphorylation of JNK,
      but not the P38 or ERK pathways. These results demonstrate the anti-inflammatory
      property of CDNF by inhibition of JNK signaling in LPS-induced microglia,
      suggesting that CDNF may be a potential novel agent for the treatment of
      neuroinflammation in the CNS disorders.

PMID- 24078521
TI  - Progress-curve analysis through integrated rate equations and its use to study
      cholinesterase reaction dynamics.
AB  - Michaelis and Menten found the direct mathematical analysis of their studied
      enzyme-catalyzed reaction unrealistic 100 years ago, and hence, they avoided this
      problem by correct adaptation and analysis of the experiment, i.e.,
      differentiation of the progress-curve data into rates. However, the most elegant
      and ideal simplification of the evaluation of kinetics parameters from progress
      curves can be performed when the algebraic integration of the rate equation
      results in an explicit mathematical equation that describes the dynamics of the
      model system of the reaction. Recently, it was demonstrated that such an
      alternative approach can be considered for enzymes that obey the generalized
      Michaelis-Menten reaction dynamics, although its use is now still limited for
      cholinesterases, which show kinetics that deviate from saturationlike hyperbolic
      behavior at high concentrations of charged substrates. However, a mathematical
      approach is reviewed here that might provide an alternative to the decades-old
      problemof data analysis of cholinesterase-catalyzed reactions, through the more
      complex Webb integrated rate equation.

PMID- 24078522
TI  - Femoroacetabular impingement: not just a square peg in a round hole.

PMID- 24078523
TI  - Achilles tendinopathy: A review of the current concepts of treatment.
AB  - The two main categories of Achilles tendon disorder are broadly classified by
      anatomical location to include non-insertional and insertional conditions. Non
      insertional Achilles tendinopathy is often managed conservatively, and many
      rehabilitation protocols have been adapted and modified, with excellent clinical
      results. Emerging and popular alternative therapies, including a variety of
      injections and extracorporeal shockwave therapy, are often combined with
      rehabilitation protocols. Surgical approaches have developed, with minimally
      invasive procedures proving popular. The management of insertional Achilles
      tendinopathy is improved by recognising coexisting pathologies around the
      insertion. Conservative rehabilitation protocols as used in non-insertional
      disorders are thought to prove less successful, but such methods are being
      modified, with improving results. Treatment such as shockwave therapy is also
      proving successful. Surgical approaches specific to the diagnosis are constantly
      evolving, and good results have been achieved.

PMID- 24078524
TI  - The current status of bracing for patients with adolescent idiopathic scoliosis.
AB  - Adolescent idiopathic scoliosis affects about 3% of children. Non-operative
      measures are aimed at altering the natural history to maintain the size of the
      curve below 40 degrees  at skeletal maturity. The application of braces to treat
      spinal deformity pre-dates the era of evidence-based medicine, and there is a
      paucity of irrefutable prospective evidence in the literature to support their
      use and their effectiveness has been questioned. This review considers this
      evidence. The weight of the evidence is in favour of bracing over observation.
      The most recent literature has moved away from addressing this question, and
      instead focuses on developments in the design of braces and ways to improve
      compliance.

PMID- 24078525
TI  - The recovery position for posterior surgery of the ankle and hindfoot.
AB  - Most posterior hindfoot procedures have been described with the patient
      positioned prone. This affords excellent access to posterior hindfoot structures
      but has several disadvantages for the management of the airway, the requirement
      for an endotracheal tube in all patients, difficulty with ventilation and an
      increased risk of pressure injuries, especially with regard to reduced ocular
      perfusion. We describe use of the 'recovery position', which affords equivalent
      access to the posterior aspect of the ankle and hindfoot without the morbidity
      associated with the prone position. A laryngeal mask rather than endotracheal
      tube may be used in most patients. In this annotation we describe this technique,
      which offers a safe and simple alternative method of positioning patients for
      posterior hindfoot and ankle surgery.

PMID- 24078526
TI  - Differences in the locations and modes of labral tearing between dysplastic hips
      and those with femoroacetabular impingement.
AB  - We investigated differences in the location and mode of labral tears between
      dysplastic hips and hips with femoroacetabular impingement (FAI). We also
      investigated the relationship between labral tear and adjacent cartilage damage.
      We retrospectively studied 72 symptomatic hips (in 68 patients: 19 men and 49
      women) with radiological evidence of dysplasia or FAI on high-resolution CT
      arthrography. The incidence and location of labral tears and modes of tear
      associated with the base of the labrum (Mode 1) or body of the labrum (Mode 2)
      were compared among FAI, mildly dysplastic and severely dysplastic hips. The
      locations predominantly involved with labral tears were different in FAI and mild
      dysplastic hips (anterior and anterosuperior zones) and in severely dysplastic
      hips (anterosuperior and superior zones) around the acetabulum. Significant
      differences were observed in the prevalence of Mode 1 versus Mode 2 tears in FAI
      hips (72% (n = 13) vs 28% (n = 5)) and severe dysplastic hips (25% (n = 2) vs 75%
      (n = 6)). The frequency of cartilage damage adjacent to Mode 1 tears was
      significantly higher (42% (n = 14)) than that adjacent to Mode 2 tears (14% (n =
      3)). Hip pathology is significantly related to the locations and modes of labral
      tears. Mode 1 tears may be a risk factor for the development of adjacent
      acetabular cartilage damage.

PMID- 24078527
TI  - Functional acetabular component position with supine total hip replacement.
AB  - Orientation of the acetabular component influences wear, range of movement and
      the incidence of dislocation after total hip replacement (THR). During surgery,
      such orientation is often referenced to the anterior pelvic plane (APP), but APP
      inclination relative to the coronal plane (pelvic tilt) varies substantially
      between individuals. In contrast, the change in pelvic tilt from supine to
      standing (dPT) is small for nearly all individuals. Therefore, in THR performed
      with the patient supine and the patient's coronal plane parallel to the operating
      table, we propose that freehand placement of the acetabular component placement
      is reliable and reflects standing (functional) cup position. We examined this
      hypothesis in 56 hips in 56 patients (19 men) with a mean age of 61 years (29 to
      80) using three-dimensional CT pelvic reconstructions and standing lateral pelvic
      radiographs. We found a low variability of acetabular component placement, with
      46 implants (82%) placed within a combined range of 30 degrees  to 50 degrees 
      inclination and 5 degrees  to 25 degrees  anteversion. Changing from the supine
      to the standing position (analysed in 47 patients) was associated with an
      anteversion change < 10 degrees  in 45 patients (96%). dPT was < 10 degrees  in
      41 patients (87%). In conclusion, supine THR appears to provide reliable freehand
      acetabular component placement. In most patients a small reclination of the
      pelvis going from supine to standing causes a small increase in anteversion of
      the acetabular component.

PMID- 24078528
TI  - Metal ion levels from well-functioning Birmingham Hip Resurfacings decline
      significantly at ten years.
AB  - A retrospective study was conducted to investigate the changes in metal ion
      levels in a consecutive series of Birmingham Hip Resurfacings (BHRs) at a minimum
      ten-year follow-up. We reviewed 250 BHRs implanted in 232 patients between 1998
      and 2001. Implant survival, clinical outcome (Harris hip score), radiographs and
      serum chromium (Cr) and cobalt (Co) ion levels were assessed. Of 232 patients, 18
      were dead (five bilateral BHRs), 15 lost to follow-up and ten had been revised.
      The remaining 202 BHRs in 190 patients (136 men and 54 women; mean age at surgery
      50.5 years (17 to 76)) were evaluated at a minimum follow-up of ten years (mean
      10.8 years (10 to 13.6)). The overall implant survival at 13.2 years was 92.4%
      (95% confidence interval 90.8 to 94.0). The mean Harris hip score was 97.7
      (median 100; 65 to 100). Median and mean ion levels were low for unilateral
      resurfacings (Cr: median 1.3 ug/l, mean 1.95 ug/l (< 0.5 to 16.2); Co: median 1.0
      ug/l, mean 1.62 ug/l (< 0.5 to 17.3)) and bilateral resurfacings (Cr: median 3.2
      ug/l, mean 3.46 ug/l (< 0.5 to 10.0); Co: median 2.3 ug/l, mean 2.66 ug/l (< 0.5
      to 9.5)). In 80 unilateral BHRs with sequential ion measurements, Cr and Co
      levels were found to decrease significantly (p < 0.001) from the initial
      assessment at a median of six years (4 to 8) to the last assessment at a median
      of 11 years (9 to 13), with a mean reduction of 1.24 ug/l for Cr and 0.88 ug/l
      for Co. Three female patients had a > 2.5 ug/l increase of Co ions, associated
      with head sizes <= 50 mm, clinical symptoms and osteolysis. Overall, there was no
      significant difference in change of ion levels between genders (Cr, p = 0.845;
      Co, p = 0.310) or component sizes (Cr, p = 0.505; Co, p = 0.370). Higher
      acetabular component inclination angles correlated with greater change in ion
      levels (Cr, p = 0.013; Co, p = 0.002). Patients with increased ion levels had
      lower Harris hip scores (p = 0.038). In conclusion, in well-functioning BHRs the
      metal ion levels decreased significantly at ten years. An increase > 2.5 ug/l was
      associated with poor function.

PMID- 24078529
TI  - Proximal tibial strain in medial unicompartmental knee replacements: A
      biomechanical study of implant design.
AB  - As many as 25% to 40% of unicompartmental knee replacement (UKR) revisions are
      performed for pain, a possible cause of which is proximal tibial strain. The aim
      of this study was to examine the effect of UKR implant design and material on
      cortical and cancellous proximal tibial strain in a synthetic bone model.
      Composite Sawbone tibiae were implanted with cemented UKR components of different
      designs, either all-polyethylene or metal-backed. The tibiae were subsequently
      loaded in 500 N increments to 2500 N, unloading between increments. Cortical
      surface strain was measured using a digital image correlation technique.
      Cancellous damage was measured using acoustic emission, an engineering technique
      that detects sonic waves ('hits') produced when damage occurs in material.
      Anteromedial cortical surface strain showed significant differences between
      implants at 1500 N and 2500 N in the proximal 10 mm only (p < 0.001), with
      relative strain shielding in metal-backed implants. Acoustic emission showed
      significant differences in cancellous bone damage between implants at all loads
      (p = 0.001). All-polyethylene implants displayed 16.6 times the total number of
      cumulative acoustic emission hits as controls. All-polyethylene implants also
      displayed more hits than controls at all loads (p < 0.001), more than metal
      backed implants at loads >= 1500 N (p < 0.001), and greater acoustic emission
      activity on unloading than controls (p = 0.01), reflecting a lack of implant
      stiffness. All-polyethylene implants were associated with a significant increase
      in damage at the microscopic level compared with metal-backed implants, even at
      low loads. All-polyethylene implants should be used with caution in patients who
      are likely to impose large loads across their knee joint.

PMID- 24078530
TI  - Unicompartmental knee replacement after high tibial osteotomy: Invalidating a
      contraindication.
AB  - The outcome of high tibial osteotomy (HTO) deteriorates with time, and additional
      procedures may be required. The aim of this study was to compare the clinical and
      radiological outcomes between unicompartmental knee replacement (UKR) and total
      knee replacement (TKR) after HTO as well as after primary UKR. A total of 63
      patients (63 knees) were studied retrospectively and divided into three groups:
      UKR after HTO (group A; n = 22), TKR after HTO (group B; n = 18) and primary UKR
      (group C; n = 22). The Oxford knee score (OKS), Knee Society score (KSS), hip
      knee-ankle angles, mechanical axis and patellar height were evaluated pre- and
      post-operatively. At a mean of 64 months (19 to 180) post-operatively the mean
      OKS was 43.8 (33 to 49), 43.3 (30 to 48) and 42.5 (29 to 48) for groups A, B and
      C, respectively (p = 0.73). The mean KSS knee score was 88.8 (54 to 100), 88.11
      (51 to 100) and 85.3 (45 to 100) for groups A, B and C, respectively (p = 0.65),
      and the mean KSS function score was 85.0 (50 to 100) in group A, 85.8 (20 to 100)
      in group B and 79.3 (50 to 100) in group C (p = 0.48). Radiologically the results
      were comparable for all groups except for patellar height, with a higher
      incidence of patella infra following a previous HTO (p = 0.02).

PMID- 24078531
TI  - Restoring the anatomical tibial slope and limb axis may maximise post-operative
      flexion in posterior-stabilised total knee replacements.
AB  - The optimal management of the tibial slope in achieving a high flexion angle in
      posterior-stabilised (PS) total knee replacement (TKR) is not well understood,
      and most studies evaluating the posterior tibial slope have been conducted on
      cruciate-retaining TKRs. We analysed pre- and post-operative tibial slope
      differences, pre- and post-operative coronal knee alignment and post-operative
      maximum flexion angle in 167 patients undergoing 209 TKRs. The mean pre-operative
      posterior tibial slope was 8.6 degrees  (1.3 degrees  to 17 degrees ) and post
      operatively it was 8.0 degrees  (0.1 degrees  to 16.7 degrees ). Multiple linear
      regression analysis showed that the absolute difference between pre- and post
      operative tibial slope (p < 0.001), post-operative coronal alignment (p = 0.02)
      and pre-operative range of movement (p < 0.001) predicted post-operative flexion.
      The variance of change in tibial slope became larger as the post-operative
      maximum flexion angle decreased. The odds ratio of having a post-operative
      flexion angle < 100 degrees  was 17.6 if the slope change was > 2 degrees . Our
      data suggest that recreation of the anatomical tibial slope appears to improve
      maximum flexion after posterior-stabilised TKR, provided coronal alignment has
      been restored.

PMID- 24078532
TI  - Patient satisfaction with total knee replacement cannot be predicted from pre
      operative variables alone: A cohort study from the National Joint Registry for
      England and Wales.
AB  - Pre-operative variables are increasingly being used to determine eligibility for
      total knee replacement (TKR). This study was undertaken to evaluate the
      relationships, interactions and predictive capacity of variables available pre-
      and post-operatively on patient satisfaction following TKR. Using nationally
      collected patient reported outcome measures and data from the National Joint
      Registry for England and Wales, we identified 22 798 patients who underwent TKR
      for osteoarthritis between August 2008 and September 2010. The ability of
      specific covariates to predict satisfaction was assessed using ordinal logistic
      regression and structural equational modelling. Only 4959 (22%) of 22 278
      patients rated the results of their TKR as 'excellent', despite the majority
      (71%, n = 15 882) perceiving their knee symptoms to be much improved. The
      strongest predictors of satisfaction were post-operative variables. Satisfaction
      was significantly and positively related to the perception of symptom improvement
      (operative success) and the post-operative EuroQol-5D score. While also
      significant within the models pre-operative variables were less important and had
      a minimal influence upon post-operative satisfaction. The most robust predictions
      of satisfaction occurred only when both pre- and post-operative variables were
      considered together. These findings question the appropriateness of restricting
      access to care based on arbitrary pre-operative thresholds as these factors have
      little bearing on post-operative satisfaction.

PMID- 24078533
TI  - The outcome of the Mobility total ankle replacement at a mean of four years: Can
      poor outcomes be predicted from pre- and post-operative analysis?
AB  - We performed a retrospective review of a consecutive series of 178 Mobility total
      ankle replacements (TARs) performed by three surgeons between January 2004 and
      June 2009, and analysed radiological parameters and clinical outcomes in a
      subgroup of 129 patients. The mean follow-up was 4 years (2 to 6.3). A total of
      ten revision procedures (5.6%) were undertaken. The mean Ankle Osteoarthritis
      Scale (AOS) pain score was 17 (0 to 88) and 86% of patients were clinically
      improved at follow-up. However, 18 patients (18 TARs, 14%) had a poor outcome
      with an AOS pain score of > 30. A worse outcome was associated with a pre
      operative diagnosis of post-traumatic degenerative arthritis. However, no pre- or
      post-operative radiological parameters were significantly associated with a poor
      outcome. Of the patients with persistent pain, eight had predominantly medial
      sided pain. Thirty TARs (29%) had a radiolucency in at least one zone. The
      outcome of the Mobility TAR at a mean of four years is satisfactory in > 85% of
      patients. However, there is a significant incidence of persistent pain,
      particularly on the medial side, for which we were unable to establish a cause.

PMID- 24078534
TI  - Use of the radial groove view intra-operatively to prevent damage to the extensor
      pollicis longus tendon by protruding screws during volar plating of a distal
      radial fracture.
AB  - The aims of this study were to assess the efficacy of a newly designed
      radiological technique (the radial groove view) for the detection of protrusion
      of screws in the groove for the extensor pollicis longus tendon (EPL) during
      plating of distal radial fractures. We also aimed to determine the optimum
      position of the forearm to obtain this view. We initially analysed the anatomy of
      the EPL groove by performing three-dimensional CT on 51 normal forearms. The mean
      horizontal angle of the groove was 17.8 degrees  (14 degrees  to 23 degrees ). We
      found that the ideal position of the fluoroscopic beam to obtain this view was 20
      degrees  in the horizontal plane and 5 degrees  in the sagittal plane. We then
      intra-operatively assessed the use of the radial groove view for detecting
      protrusion of screws in the EPL groove in 93 fractures that were treated by volar
      plating. A total of 13 protruding screws were detected. They were changed to
      shorter screws and these patients underwent CT scans of the wrist immediately
      post-operatively. There remained one screw that was protruding. These findings
      suggest that the use of the radial groove view intra-operatively is a good method
      of assessing the possible protrusion of screws into the groove of EPL when
      plating a fracture of the distal radius.

PMID- 24078535
TI  - Three-dimensional assessment of the dimensions of the osteoarthritic glenoid.
AB  - Osteoarthritis results in changes in the dimensions of the glenoid. This study
      aimed to assess the size and radius of curvature of arthritic glenoids. A total
      of 145 CT scans were analysed, performed as part of routine pre-operative
      assessment before total shoulder replacement in 91 women and 54 men. Only
      patients with primary osteoarthritis and a concentric glenoid were included in
      the study. The CT scans underwent three-dimensional (3D) reconstruction and were
      analysed using dedicated computer software. The measurements consisted of maximum
      superoinferior height, anteroposterior width and a best-fit sphere radius of
      curvature of the glenoid. The mean height was 40.2 mm (SD 4.9), the mean width
      was 29 mm (SD 4.3) and the mean radius of curvature was 35.4 mm (SD 7.8). The
      measurements were statistically different in men and women and had a Gaussian
      distribution with marked variation. All measurements were greater than the known
      values in normal subjects. With current shoulder replacement systems using a
      unique backside radius of curvature for the glenoid component, there is a risk of
      undertaking excessive reaming to adapt the bone to the component resulting in
      sacrifice of subchondral bone or under-reaming and instability of the component
      due to a 'rocking horse' phenomenon.

PMID- 24078536
TI  - The effect of excision of the radial head and metallic radial head replacement on
      the tension in the interosseous membrane.
AB  - We measured the tension in the interosseous membrane in six cadaveric forearms
      using an in vitro forearm testing system with the native radial head, after
      excision of the radial head and after metallic radial head replacement. The
      tension almost doubled after excision of the radial head during simulated
      rotation of the forearm (p = 0.007). There was no significant difference in
      tension in the interosseous membrane between the native and radial head
      replacement states (p = 0.09). Maximal tension occurred in neutral rotation with
      both the native and the replaced radial head, but in pronation if the radial head
      was excised. Under an increasing axial load and with the forearm in a fixed
      position, the rate of increase in tension in the interosseous membrane was
      greater when the radial head was excised than for the native radial head or
      replacement states (p = 0.02). As there was no difference in tension between the
      native and radial head replacement states, a radial head replacement should
      provide a normal healing environment for the interosseous membrane after injury
      or following its reconstruction. Load sharing between the radius and ulna becomes
      normal after radial head Replacement. As excision of the radial head
      significantly increased the tension in the interosseous membrane it may
      potentially lead to its attritional failure over time.

PMID- 24078537
TI  - Neurological deterioration due to missed thoracic spinal stenosis after
      decompressive lumbar surgery: A report of six cases of tandem thoracic and lumbar
      spinal stenosis.
AB  - There have been a few reports of patients with a combination of lumbar and
      thoracic spinal stenosis. We describe six patients who suffered unexpected acute
      neurological deterioration at a mean of 7.8 days (6 to 10) after lumbar
      decompressive surgery. Five had progressive weakness and one had recurrent pain
      in the lower limbs. There was incomplete recovery following subsequent thoracic
      decompressive surgery. The neurological presentation can be confusing. Patients
      with compressive myelopathy due to lower thoracic lesions, especially epiconus
      lesions (T10 to T12/L1 disc level), present with similar symptoms to those with
      lumbar radiculopathy or cauda equina lesions. Despite the rarity of this
      condition we advise that patients who undergo lumbar decompressive surgery for
      stenosis should have sagittal whole spine MRI studies pre-operatively to exclude
      proximal neurological compression.

PMID- 24078538
TI  - Total spondylectomy following carbon ion radiotherapy to treat chordoma of the
      mobile spine.
AB  - The main form of treatment of a chordoma of the mobile spine is total en bloc
      spondylectomy (TES), but the clinical results are not satisfactory. Stand-alone
      carbon ion radiotherapy (CIRT) for bone and soft-tissue sarcomas has recently
      been reported to have a high rate of local control with a low rate of local
      recurrence. We report two patients who underwent TES after CIRT for treating a
      chordoma in the lumbar spine with good medium-term outcomes. At operation, there
      remained histological evidence of viable tumour cells in both cases. After the
      combination use of TES following CIRT, neither patient showed signs of recurrence
      at the follow-up examination. These two cases suggest that CIRT should be
      combined with total spondylectomy in the treatment of chordoma of the mobile
      spine.

PMID- 24078539
TI  - The imaging and classification of severe pelvic ring fractures: Experiences from
      two level 1 trauma centres.
AB  - We describe the routine imaging practices of Level 1 trauma centres for patients
      with severe pelvic ring fractures, and the interobserver reliability of the
      classification systems of these fractures using plain radiographs and three
      dimensional (3D) CT reconstructions. Clinical and imaging data for 187 adult
      patients (139 men and 48 women, mean age 43 years (15 to 101)) with a severe
      pelvic ring fracture managed at two Level 1 trauma centres between July 2007 and
      June 2010 were extracted. Three experienced orthopaedic surgeons classified the
      plain radiographs and 3D CT reconstruction images of 100 patients using the
      Tile/AO and Young-Burgess systems. Reliability was compared using kappa
      statistics. A total of 115 patients (62%) had plain radiographs as well as two
      dimensional (2D) CT and 3D CT reconstructions, 52 patients (28%) had plain films
      only, 12 (6.4%) had 2D and 3D CT reconstructions images only, and eight patients
      (4.3%) had no available images. The plain radiograph was limited to an
      anteroposterior pelvic view. Patients without imaging, or only plain films, were
      more severely injured. A total of 72 patients (39%) were imaged with a pelvic
      binder in situ. Interobserver reliability for the Tile/AO (Kappa 0.10 to 0.17)
      and Young-Burgess (Kappa 0.09 to 0.21) was low, and insufficient for clinical and
      research purposes. Severe pelvic ring fractures are difficult to classify due to
      their complexity, the increasing use of early treatment such as with pelvic
      binders, and the absence of imaging altogether in important patient sub-groups,
      such as those who die early of their injuries.

PMID- 24078540
TI  - Internal fixation of intracapsular fractures of the hip using a dynamic locking
      plate: Two-year follow-up of 320 patients.
AB  - A consecutive series of 320 patients with an intracapsular fracture of the hip
      treated with a dynamic locking plate (Targon Femoral Neck (TFN)) were reviewed.
      All surviving patients were followed for a minimum of two years. During the
      follow-up period 109 patients died. There were 112 undisplaced fractures, of
      which three (2.7%) developed nonunion or re-displacement and five (4.5%)
      developed avascular necrosis of the femoral head. Revision to an arthroplasty was
      required for five patients (4.5%). A further six patients (5.4%) had elective
      removal of the plate and screws. There were 208 displaced fractures, of which 32
      (15.4%) developed nonunion or re-displacement and 23 (11.1%) developed avascular
      necrosis. A further four patients (1.9%) developed a secondary fracture around
      the TFN. Revision to a hip replacement was required for 43 patients (20.7%)
      patients and a further seven (3.3%) had elective removal of the plate and screws.
      It is suggested that the stronger distal fixation combined with rotational
      stability may lead to a reduced incidence of complications related to the healing
      of the fracture when compared with other contemporary fixation devices but this
      needs to be confirmed in further studies.

PMID- 24078541
TI  - A laboratory investigation to assess the influence of cement augmentation of
      screw and plate fixation in a simulation of distal femoral fracture of
      osteoporotic and non-osteoporotic bone.
AB  - The augmentation of fixation with bone cement is increasingly being used in the
      treatment of severe osteoporotic fractures. We investigated the influence of bone
      quality on the mechanics of augmentation of plate fixation in a distal femoral
      fracture model (AO 33 A3 type). Eight osteoporotic and eight non-osteoporotic
      femoral models were randomly assigned to either an augmented or a non-augmented
      group. Fixation was performed using a locking compression plate. In the augmented
      group additionally 1 ml of bone cement was injected into the screw hole before
      insertion of the screw. Biomechanical testing was performed in axial sinusoidal
      loading. Augmentation significantly reduced the cut-out distance in the
      osteoporotic models by about 67% (non-augmented mean 0.30 mm (sd 0.08) vs
      augmented 0.13 mm (sd 0.06); p = 0.017). There was no statistical reduction in
      this distance following augmentation in the non-osteoporotic models (non
      augmented mean 0.15 mm (sd 0.02) vs augmented 0.15 mm (sd 0.07); p = 0.915). In
      the osteoporotic models, augmentation significantly increased stability (p =
      0.017).

PMID- 24078542
TI  - Pelvic reconstruction with compound osteosynthesis following hemipelvectomy: A
      clinical study.
AB  - To date, all surgical techniques used for reconstruction of the pelvic ring
      following supra-acetabular tumour resection produce high complication rates. We
      evaluated the clinical, oncological and functional outcomes of a cohort of 35
      patients (15 men and 20 women), including 21 Ewing's sarcomas, six
      chondrosarcomas, three sarcomas not otherwise specified, one osteosarcoma, two
      osseous malignant fibrous histiocytomas, one synovial cell sarcoma and one
      metastasis. The mean age of the patients was 31 years (8 to 79) and the latest
      follow-up was carried out at a mean of 46 months (1.9 to 139.5) post-operatively.
      We undertook a functional reconstruction of the pelvic ring using polyaxial
      screws and titanium rods. In 31 patients (89%) the construct was encased in
      antibiotic-impregnated polymethylmethacrylate. Preservation of the extremities
      was possible for all patients. The survival rate at three years was 93.9% (95%
      confidence interval (CI) 77.9 to 98.4), at five years it was 82.4% (95% CI 57.6
      to 93.4). For the 21 patients with Ewing's sarcoma it was 95.2% (95% CI 70.7 to
      99.3) and 81.5% (95% CI 52.0 to 93.8), respectively. Wound healing problems were
      observed in eight patients, deep infection in five and clinically asymptomatic
      breakage of the screws in six. The five-year implant survival was 93.3% (95% CI
      57.8 to 95.7). Patients were mobilised at a mean of 3.5 weeks (1 to 7) post
      operatively. A post-operative neurological defect occurred in 12 patients. The
      mean Musculoskeletal Tumor Society score at last available follow-up was 21.2 (10
      to 27). This reconstruction technique is characterised by simple and
      oncologically appropriate applicability, achieving high primary stability that
      allows early mobilisation, good functional results and relatively low
      complication rates.

PMID- 24078543
TI  - Can computer navigation-assisted surgery reduce the risk of an intralesional
      margin and reduce the rate of local recurrence in patients with a tumour of the
      pelvis or sacrum?
AB  - We hypothesised that the use of computer navigation-assisted surgery for pelvic
      and sacral tumours would reduce the risk of an intralesional margin. We reviewed
      31 patients (18 men and 13 women) with a mean age of 52.9 years (13.5 to 77.2) in
      whom computer navigation-assisted surgery had been carried out for a bone tumour
      of the pelvis or sacrum. There were 23 primary malignant bone tumours, four
      metastatic tumours and four locally advanced primary tumours of the rectum. The
      registration error when using computer navigation was < 1 mm in each case. There
      were no complications related to the navigation, which allowed the preservation
      of sacral nerve roots (n = 13), resection of otherwise inoperable disease (n = 4)
      and the avoidance of hindquarter amputation (n = 3). The intralesional resection
      rate for primary tumours of the pelvis and sacrum was 8.7% (n = 2): clear bone
      resection margins were achieved in all cases. At a mean follow-up of 13.1 months
      (3 to 34) three patients (13%) had developed a local recurrence. The mean time
      alive from diagnosis was 16.8 months (4 to 48). Computer navigation-assisted
      surgery is safe and has reduced our intralesional resection rate for primary
      tumours of the pelvis and sacrum. We recommend this technique as being worthy of
      further consideration for this group of patients.

PMID- 24078544
TI  - Endoprosthetic replacement after extra-articular resection of bone and soft
      tissue tumours around the knee.
AB  - We evaluated the clinical results and complications after extra-articular
      resection of the distal femur and/or proximal tibia and reconstruction with a
      tumour endoprosthesis (MUTARS) in 59 patients (mean age 33 years (11 to 74)) with
      malignant bone or soft-tissue tumours. According to a Kaplan-Meier analysis, limb
      survival was 76% (95% confidence interval (CI) 64.1 to 88.5) after a mean follow
      up of 4.7 years (one month to 17 years). Peri-prosthetic infection was the most
      common indication for subsequent amputation (eight patients). Survival of the
      prosthesis without revision was 48% (95% CI 34.8 to 62.0) at two years and 25%
      (95% CI 11.1 to 39.9) at five years post-operatively. Failure of the prosthesis
      was due to deep infection in 22 patients (37%), aseptic loosening in ten patients
      (17%), and peri-prosthetic fracture in six patients (10%). Wear of the bearings
      made a minor revision necessary in 12 patients (20%). The mean Musculoskeletal
      Tumor Society score was 23 (10 to 29). An extensor lag > 10 degrees  was noted in
      ten patients (17%). These results suggest that limb salvage after extra-articular
      resection with a tumour prosthesis can achieve good functional results in most
      patients, although the rates of complications and subsequent amputation are
      higher than in patients treated with intra-articular resection.

PMID- 24078545
TI  - Surgical correction of a rotational deformity of the shoulder in patients with
      obstetric brachial plexus palsy: Short-term results in 270 patients.
AB  - We evaluated results at one year after surgical correction of internal rotation
      deformities in the shoulders of 270 patients with obstetric brachial plexus
      palsy. The mean age at surgery was 6.2 years (0.6 to 35). Two techniques were
      used: open subscapularis elongation and latissimus dorsi to infraspinatus
      transfer. In addition, open relocation was performed or attempted in all patients
      with subluxed or dislocated joints. A mixed effects model approach was used to
      evaluate the effects of surgery on internal and external rotation, abduction,
      flexion and Mallet score. Independent factors included operative status (pre- or
      post-operative), gender, age, the condition of the joint, and whether or not
      transfer was performed. The overall mean improvement in external rotation
      following surgery was 84.6 degrees  (95% confidence interval (CI) 80.2 to 89.1)
      and the mean Mallet score improved by 4.0 (95% CI 3.7 to 4.2). There was a mean
      decrease in internal rotation of between 27.6 degrees  and 34.4 degrees  in the
      relocated joint groups and 8.6 degrees  (95% CI 5.2 to 12.0) in the normal joint
      group. Abduction and flexion were unchanged following surgery. Adding a
      latissimus dorsi transfer did not result in greater improvement in the mean
      external rotation compared with elongation of the subscapularis alone.

PMID- 24078547
TI  - Am I still a scientist?

PMID- 24078548
TI  - The--YENPTY--domain of the amyloid precursor protein: much more than just
      endocytosis?

PMID- 24078552
TI  - Mass spectrometric study of the gas-phase difluorocarbene expulsion of
      polyfluorophenyl cations via F-atom migration.
AB  - An increasing number of fluorinated drugs, pesticides, and fine chemicals are now
      produced and applied, especially those containing polyfluorinated aromatic
      moieties. However, at present, the extent of literature covering the special mass
      spectrometric behaviors of these compounds remains limited. Herein, we report an
      unexpected but also general gas-phase dissociation mode of polyfluorinated
      aromatics in mass spectrometry: expulsion of difluorocarbene (50-Da neutral
      loss). Results from accurate mass measurements, tandem mass spectrometric
      experiments, and density functional theory (DFT) calculations support an
      intramolecular F-atom "ring-walk" migration mechanism for gas-phase CF2 loss.
      Based on an assessment of the electron ionization-mass spectrometry (EI-MS) data
      of more than 40 polyfluorinated aromatic compounds from the National Institute of
      Standards and Technology data bank, we generalized on the substitution group
      effects on the difluorocarbene dissociation process of polyfluorinated aromatic
      compounds in EI-MS. These studies have enriched our knowledge of the special gas
      phase reactivity of polyfluorinated aromatics and will provide valuable
      information in further analytical research of these compounds by mass
      spectrometry.

PMID- 24078553
TI  - Complete obstruction to flow in a three-way stopcock due to a manufacturing
      defect.

PMID- 24078554
TI  - The fentanyl concentration required for immobility under propofol anesthesia is
      reduced by pre-treatment with flurbiprofen axetil.
AB  - PURPOSE: We hypothesized that nonsteroidal anti-inflammatory drugs decrease the
      plasma fentanyl concentration required to produce immobility in 50% of patients
      in response to skin incision (Cp50incision) compared with placebo under target
      controlled infusion (TCI) propofol anesthesia. METHODS: Sixty-two unpremedicated
      patients scheduled to undergo gynecologic laparoscopy were randomly assigned to
      receive placebo (control group) or flurbiprofen axetil 1 mg.kg(-1) (flurbiprofen
      group) preoperatively. General anesthesia was induced with fentanyl and propofol,
      and intubation was performed after succinylcholine 1 mg.kg(-1). Propofol was
      administered via a target-controlled infusion (TCI) system (DiprifusorTM) set at
      an effect-site concentration of 5 MUg.mL(-1). Fentanyl was given by a TCI system
      using the STANPUMP software (Schafer model). The concentration for the first
      patient was set at 3 ng.mL(-1) and modified in each group according to the up
      down method. Skin incision was performed after more than ten minutes
      equilibration time. Serum fentanyl concentration, bispectral index (BIS), and
      hemodynamic parameters were measured two minutes before and after skin incision.
      The Cp50incision of fentanyl was derived from the mean of the crossovers (i.e.,
      the serum fentanyl concentrations of successive participants who responded and
      those who did not or vice versa). RESULTS: Ten and 11 independent crossover pairs
      were collected in the control and flurbiprofen groups, respectively, representing
      42 of 62 enrolled patients. The mean (SD) fentanyl Cp50incision was less in the
      flurbiprofen group [0.84 (0.63) ng.mL(-1)] than in the control group [1.65 (1.15)
      ng.mL(-1)]; P = 0.007; however, there were no differences in BIS, blood pressure,
      or heart rate, between groups. CONCLUSION: Preoperative flurbiprofen axetil
      decreased the Cp50incision of fentanyl by 49% during propofol anesthesia without
      changing the BIS or hemodynamic variables.

PMID- 24078555
TI  - Relation of neutrophil-to-lymphocyte ratio with GRACE risk score to in-hospital
      cardiac events in patients with ST-segment elevated myocardial infarction.
AB  - In this study, we aimed to investigate the association of the neutrophil-to
      lymphocyte ratio (NLR) with Global Registry of Acute Coronary Events (GRACE) risk
      score in patients with ST-segment elevated myocardial infarction (STEMI). We
      analyzed 101 consecutive patients with STEMI. Patients were divided into 3 groups
      by use of GRACE risk score. The association between NLR and GRACE risk score was
      assessed. The NLR showed a proportional increase correlated with GRACE risk score
      (P < .001). The occurrence of in-hospital cardiac death, reinfarction, or new
      onset heart failure was significantly related to NLR at admission (P < .001).
      Likewise, NLR and GRACE risk score showed a significant positive correlation (r =
      .803, P < .001). In multivariate analysis, NLR resulted as a predictor of worse
      in-hospital outcomes independent of GRACE risk score. Our study suggests that the
      NLR is significantly associated with adverse in-hospital outcomes, independent of
      GRACE risk score in patients with STEMI. 

PMID- 24078556
TI  - HIV clades B and C are associated with reduced brain volumetrics.
AB  - The human immunodeficiency virus (HIV) has multiple genetic clades with varying
      prevalence throughout the world. Both HIV clade C (HIV-C) and HIV clade B (HIV-B)
      can cause cognitive impairment, but it is unclear if these clades are
      characterized by similar patterns of brain dysfunction. We examined brain
      volumetrics and neuropsychological performance among highly active antiretroviral
      therapy (HAART)-naive HIV-B and HIV-C participants. Thirty-four HAART-naive HIV
      infected (HIV+) participants [17 HIV-B (USA); 17 HIV-C (South Africa)] and 34 age
      and education-matched HIV-uninfected (HIV-) participants were evaluated. All
      participants underwent similar laboratory, neuropsychological, and neuroimaging
      studies. Brain volume measures were assessed within the caudate, putamen,
      amygdala, thalamus, hippocampus, corpus callosum, and cortical (gray and white
      matter) structures. A linear model that included HIV status, region, and their
      interaction assessed the effects of the virus on brain volumetrics. HIV- and HIV+
      individuals were similar in age. On laboratory examination, HIV-C participants
      had lower CD4 cell counts and higher plasma HIV viral loads than HIV-B
      individuals. In general, HIV+ participants performed significantly worse on
      neuropsychological measures of processing speed and memory and had significantly
      smaller relative volumetrics within the thalamus, hippocampus, corpus callosum,
      and cortical gray and white matter compared to the respective HIV- controls. Both
      HIV-B and HIV-C are associated with similar volumetric declines when compared to
      matched HIV- controls. HIV-B and HIV-C were associated with significant
      reductions in brain volumetrics and poorer neuropsychological performance;
      however, no specific effect of HIV clade subtype was evident. These findings
      suggest that HIV-B and HIV-C both detrimentally affect brain integrity.

PMID- 24078557
TI  - Dual-mixed HIV-1 coreceptor tropism and HIV-associated neurocognitive deficits.
AB  - HIV coreceptor usage of CXCR4 (X4) is associated with decreased CD4+ T-cell
      counts and accelerated disease progression, but the role of X4 tropism in HIV
      associated neurocognitive disorders (HAND) has not previously been described.
      This longitudinal study evaluated data on 197 visits from 72 recently HIV
      infected persons who had undergone up to four sequential neurocognitive
      assessments over a median of 160 days (IQR, 138-192). Phenotypic tropism testing
      (Trofile ES, Monogram, Biosciences) was performed on stored blood samples.
      Multivariable mixed model repeated measures regression was used to determine the
      association between HAND and dual-mixed (DM) viral tropism, estimated duration of
      infection (EDI), HIV RNA, CD4 count, and problematic methamphetamine use. Six
      subjects (8.3 %) had DM at their first neurocognitive assessment and four
      converted to DM in subsequent sampling (for total of 10 DM) at a median EDI of
      10.1 months (IQR, 7.2-12.2). There were 44 (61.1 %) subjects who demonstrated
      HAND on at least one study visit. HAND was associated with DM tropism (odds
      ratio, 4.4; 95 % CI, 0.9-20.5) and shorter EDI (odds ratio 1.1 per month earlier;
      95 % CI, 1.0-1.2). This study found that recency of HIV-1 infection and the
      development of DM tropism may be associated with HAND in the relatively early
      stage of infection. Together, these data suggest that viral interaction with
      cellular receptors may play an important role in the early manifestation of HAND.

PMID- 24078559
TI  - Older individuals with HIV infection have greater memory deficits than younger
      individuals.
AB  - The prevalence of HIV-associated neurocognitive disorder (HAND) remains
      persistently high in the era of combination antiretroviral therapy. We aimed to
      characterize the pattern of neurocognitive dysfunction in older subjects with
      HAND in particular amnestic versus non-amnestic impairment. One hundred six
      subjects from the Johns Hopkins University NIMH Clinical Outcomes cohort
      underwent standardized neuropsychological (NP) testing between November 2006 and
      June 2010. We examined performance in seven cognitive domains (memory, attention,
      speed of processing,visuospatial, language, motor, and executive). Older subjects
      were defined as age >50 years at the time of NP testing.Subjects were diagnosed
      with HAND according to established criteria and dichotomized into amnestic
      cognitive impairment or non-amnestic cognitive impairment with deficit defined as
      z scores <-1.5 for the verbal and nonverbal memory domains.There were 32 older
      subjects with a mean age (SD) of 54.2 (2.8) years and 74 younger subjects, 43.7
      (4.3) years. Older age was associated with a 4.8-fold higher odds of memory
      deficits adjusted for potential confounders (p =0.035) identified a priori. With
      age modeled as a continuous covariate,every 1 year increase in age was associated
      with a 1.11-fold higher odds of memory deficit (p =0.05). There was a higher
      proportion of amnestic cognitive impairment among older subjects than younger
      subjects with HIV infection. Neurodegenerative processes other than those
      directly due to HIV maybe increasingly important as individuals with chronic HIV
      infection and HAND survive into older age.

PMID- 24078560
TI  - [Characteristics of RB1 gene mutations in Chinese patients with retinoblastoma].
AB  - OBJECTIVE: To study the characteristics of RB1 gene mutations in Chinese patients
      with retinoblastoma. METHODS: Peripheral blood samples of 35 patients with
      retinoblastoma were collected and genomic DNA was extracted. Multiplex PCR
      sequencing was carried out to identify RB1 gene mutations. Parents of 6 probands
      with RB1 mutations were also enrolled to identify the origins of mutations.
      RESULTS: Fourteen patients were found to have carried germline mutations, among
      whom 11 had bilateral tumors and 3 had unilateral tumors. Sixteen germline
      mutations were identified, among which 13 were pathological, which included 5
      nonsense mutations (c.1072C > T, c.1333C > T, c.1363C > T, c.1399C > T, c.2501C >
      A), 4 missense mutations (c.920C > T, c.1346G > A, c.1468G > A, c.1861C > A), 2
      frameshift mutations (c.1947delG, c.2403delA) and 2 large fragment deletions
      (c.139_168 del30, exon 8 deletion). Three were non-pathological mutations,
      including 2 intronic mutations (c.540-23 dupT, c.2664-10T > A) and 1 silent
      mutation (c.2192T > A). One carrier was identified among the 6 parents of
      children carrying a RB1 mutation. CONCLUSION: Screening for RB1 gene mutations in
      patients with bilateral or unilateral retinoblastoma can help to identify
      heritable mutations and provide important clues for genetic counseling and
      clinical management.

PMID- 24078558
TI  - HIV-related cognitive impairment shows bi-directional association with dopamine
      receptor DRD1 and DRD2 polymorphisms in substance-dependent and substance
      independent populations.
AB  - It has been postulated that drugs of abuse act synergistically with HIV, leading
      to increased neurotoxicity and neurocognitive impairment. The CNS impacts of HIV
      and drug use converge on the mesocorticolimbic dopamine (DA) system, which
      contains two main receptor subtypes: dopamine receptors 1 (DRD1) and 2 (DRD2).
      DRD1 and DRD2 have been linked to substance dependence; whether they predict HIV
      associated neurocognitive disorder (HAND) is unclear. Using an advanced-stage
      HIV+ population, we sought to determine if drug dependence impacts the
      contribution of DA receptor polymorphisms on neurocognition. We observed that
      both DRD1 and DRD2 polymorphisms were associated with opiate and cocaine
      dependence (P < 0.05) in Caucasian subjects, but not African-American
      individuals. Using linear regression analysis, we examined the polymorphisms for
      associations with neuropsychological performance in global and cognitive domain T
      scores (Motor, Processing Speed, Verbal Fluency, Learning, Memory, Executive
      Functioning, Working Memory) while controlling for opiate and cocaine dependency.
      In the Motor domain, we observed an association for two DRD2 polymorphisms (P <
      0.05) in Caucasian subjects. The effects differed for substance dependence groups
      as the direction of the correlations with DRD2 were opposite to what was seen in
      subjects without these dependencies. In African-American subjects, associations
      were observed in nearly every domain, and again, the direction of the correlation
      differed between substance-dependent and substance-independent groups. We
      conclude that studies to examine genetic risk for HAND must carefully account for
      substance dependence patterns when assaying dopaminergic systems, as the
      neurobiological substrates of cognition in HIV populations may vary with tonic
      alterations secondary to chronic substance exposures.

PMID- 24078561
TI  - [Mutational spectrum of phenylalanine hydroxylase gene and identification of
      novel mutations in patients with hyperphenylalaninemia in Jiangsu province].
AB  - OBJECTIVE: To study the characteristics of phenylalanine hydroxylase (PAH) gene
      mutations in patients with hyperphenylalaninemia from Jiangsu province by DNA
      sequencing, and to analyze the spectrum of PAH gene mutations. METHODS: A total
      of 70 patients and their parents were included in this study. All of the 13 exons
      and flanking introns of the PAH gene were analyzed with DNA sequencing. RESULTS:
      Forty five types of mutations were identified, which included 4 novel mutations
      (L37P, H107R, Q267L, S391T). A total of 125 mutations were identified in 140
      alleles (89.3%). All mutations were detected in exons 2-3, 5-7, 9-12 and introns
      2, 4, 7 and 8. Most mutations were found in exons 6, 7 and 12. EX6-96A > G, R243Q
      and R241C were the most common mutations. CONCLUSION: The mutational spectrum of
      Jiangsu province seems to be different from other regions. The spectrum can offer
      reliable information for genetic diagnosis of patients with
      hyperphenylalaninemia.

PMID- 24078562
TI  - [Genetic analysis and prenatal diagnosis for non-syndromic hearing impairment].
AB  - OBJECTIVE: To detect genetic mutations underlying non-syndromic hearing
      impairment (NSHI) and establish a method for prenatal diagnosis. METHODS: Sixty
      six NSHI patients were included in this study. DNA was extracted from peripheral
      blood. Genetic mutations were detected by gene chip analysis and direct
      sequencing of GJB2 gene. For 7 pregnant women at high risk, prenatal genetic
      diagnosis was provided. RESULTS: Fourteen cases (21.21%) were found to have GJB2
      mutations by both methods (homozygous 235delC mutation in 3 cases, homozygous
      176del16 mutation in 2 cases, 235delC and 299delAT compound heterozygous mutation
      in 2 cases, 299delAT and 176del16 compound heterozygous mutation in 1 case,
      c.339T > G and 313del12bp compound heterozygous mutation 1 case, and 235delC
      heterozygous mutation in 5 cases). 13 (19.70%) had SLC26A4 mutations (IVS7-2 A >G
      homozygous mutation in 2 cases, IVS7-2 A > G homozygous mutation in 2 cases, IVS7
      2 A > G and 2168A > G compound heterozygous mutation in 3 cases, 2168A>G
      heterozygous mutation in 3 cases, and IVS7-2 heterozygous mutation in 3 cases);
      and 3 had mtDNA12S rRNA mutation (1555A > G mutation in 2 cases, 1494C > T
      mutation in 1 case). Prenatal diagnosis suggested that 3 fetuses have carried a
      heterozygous mutation. Two fetuses were detected as normal and confirmed to have
      normal hearing after birth. Two fetuses were found to have carried compound
      mutations of GJB2. CONCLUSION: Gene chip combined with GJB2 gene analysis is an
      accurate and effective method for the diagnosis of NSHI. The results can
      facilitate accurate prenatal diagnosis.

PMID- 24078563
TI  - [Efficiency of multi-round fluorescence in situ hybridization and its influencing
      factors in preimplantation genetic diagnosis].
AB  - OBJECTIVE: To investigate the efficiency of multi-round fluorescence in situ
      hybridization (FISH) and its influencing factors in preimplantation genetic
      diagnosis (PGD). METHODS: A total of 48 couples accepted PGD because of various
      reasons: 24 with Robertsonian translocations, 16 with reciprocal translocations,
      2 with pericentric inversions, one with advanced maternal age who had a previous
      liveborn of Down syndrome, 3 suffered from sex chromosome abnormalities and 2
      repeated spontaneous miscarriages. After 72 retrieval cycles, 432 cleavage stage
      embryos with more than six cells were biopsied on day three. Only intact nuclei
      (396) were hybridized in order to verify the chromosomal status of the individual
      embryos. If previous FISH has failed to give conclusive results while the nuclei
      remained undamaged, the nuclei were hybridized once again. A total of 870 times
      of hybridization were conducted to 396 nuclei. Signal identification rates of
      each round as well as the influence of different probes to the hybridization
      efficiency were compared. Factors leading to inconclusive FISH results were
      analyzed as well. RESULTS: Five hundred and thirty five out of 870 hybridizations
      gave identifiable signals (61.5%). The second and third round FISH showed the
      best signals with an identification rate of 71.8% and 77.4%, respectively, which
      were significantly higher than those of the first round (52.8%, P < 0.01), the
      fourth round (55.8%, P < 0.05, P < 0.01), the fifth round (54.5%, P < 0.05) and
      the sixth round (27.3%, P < 0.01). The identification rate of centromere specific
      probe signals (CEP group) was 80.3% and the former three rounds in this group got
      the best quality of signals with an identification rate of 85.7%, 85.1% and
      88.0%, respectively, which was significantly higher than that of the latter three
      rounds. The identification rate of other probe was much lower than with the CEP
      probe (55.2% vs. 80.3%, P < 0.01) and the best quality of signal in this group
      was achieved in the fifth round (72.7%), followed by the second round (66.1%) and
      the third round (63.8%). The identification rate of the first round (50.3%) and
      the sixth round (22.2%) were significantly lower compared with the second round
      (P < 0.01). During the 6 rounds of FISH, 335 hybridizations did not give
      conclusion results (38.5%, 335/870). The main cause of unidentification was weak
      signals (20.9%, 182/870). Other common factors included background interference
      (7.6%, 66/870) and failed hybridization (6.1%, 53/870). Rare causes included
      nucleus damage (1.8%, 16/870), nucleus loss (1.1%, 10/870) and signal
      split/overlap (0.9%, 8/870). CONCLUSION: Multi-round FISH can improve the utility
      of single nucleus in PGD and the former three rounds have the highest efficiency.
      The hybridization effect of CEP is better than other probe. Poor signal quality
      is the common cause of unidentification results.

PMID- 24078565
TI  - [Mutation analysis and prenatal diagnosis of FBN1 gene mutations for four
      patients with Marfan syndrome].
AB  - OBJECTIVE: To screen for mutations of fibrillin-1 (FBN1) gene in 4 patients with
      Marfan syndrome in order to provide prenatal diagnosis and genetic counseling.
      METHODS: Potential mutations of the FBN1 gene in the probands were detected with
      PCR and DNA sequencing. Subsequently, genomic DNA was extracted from amniotic
      fluid sampled between 18 to 20 weeks gestation. The mutations were confirmed with
      denaturing high-performance liquid chromatography - robust microsatellite
      instability (DHPLC-MSI) analysis with maternal DNA as reference. The products
      were further analyzed by direct sequencing and BLAST search of NCBI database.
      RESULTS: An IVS46+1G>A substitution was identified in patient A at +1 position of
      intron 46 of the FBN1 gene. Two novel missense mutations were respectively
      discovered at positions +4453 of intron 35 in patient B (Cys1485Gly) and position
      +2585 of intron 21 in patient C (Cys862Tyr). In patient D, a novel deletion
      (c.3536 delA) was found at position +3536 of intron 28. In all of the 4 cases,
      the same mutations have been identified in the fetuses. CONCLUSION: FBN1 gene
      analysis can provide accurate diagnosis of Marfan syndrome, which can facilitate
      both prenatal diagnosis and genetic counseling.

PMID- 24078564
TI  - [Rapid screening for MTHFR gene 677C>T polymorphism in Down syndrome using high
      resolution melting curve and pyrosequencing].
AB  - OBJECTIVE: To establish a rapid method for detecting MTHFR gene 677C>T
      polymorphisms with high-resolution melting curve method (HRM) and pyrosequencing.
      METHODS: Peripheral blood samples were collected from 155 Down syndrome patients
      and 182 normal controls from Children's Hospital of Shanghai. The accuracy of
      three methods including regular HRM, internal control HRM and artificial
      heterozygosity HRM was compared. Meanwhile, allele frequencies in 10, 30 and 50
      mixed samples were measured with pyrosequencing, and the results were compared
      with that of HRM. RESULTS: Heterozygosity of 677C>T polymorphism could be
      distinguished by various HRM methods. However, homozygotes CC and TT were only
      identifiable by internal control HRM and artificial heterozygosity HRM. The
      accuracy of pyrosequencing for allele frequency has improved with increased
      sample number. When the number of mixed samples has exceeded 30, the difference
      between pyrosequencing results and actual values became less than 4%. TT genotype
      was more frequent in Down syndrome patients than controls (25.2% vs. 14.3%). No
      significant difference was found in T allele frequency between the two groups
      (44.9% vs. 40.1%). CONCLUSION: Respectively, internal control HRM and
      pyrosequencing may be ideal methods for determination of genotypic and allelic
      frequencies.

PMID- 24078566
TI  - [Analysis of small supernumerary marker chromosome 15q11 in four infertile
      males].
AB  - OBJECTIVE: To delineate the origins of small supernumerary marker chromosomes
      (sSMCs) identified in 4 infertile males. METHODS: The sSMCs were analyzed with
      combined G-banding, N-banding, multiplex ligation-dependent probe amplification
      (MLPA), fluorescence in situ hybridization (FISH) and single nucleotide
      polymorphisms array (SNP-array) techniques. RESULTS: G-banding analysis has
      suggested a 46,X,-Y,+mar karyotype in all of the 4 cases. N-banding revealed that
      all of the sSMCs have possessed two satellites located on both sides. By MLPA, 1
      patient showed copy number gains for 15q11.2 region. SNP-array analysis suggested
      that all had duplication for 15q11.1-q11.2 region, spanning 3.06 Mb, 0.9118 Mb,
      1.728 Mb and 0.287 Mb, respectively. By FISH analysis, all of the sSMCs showed
      two hybridization signals, indicating that they were dicentric chromosomes.
      CONCLUSION: In all of the four cases, the marker chromosomes have derived from
      chromosome 15 and were bisatellited and dicentric, which gave rise to a karyotype
      of 47,XY,+ish,inv dup(15)(q11)(D15Z4++). sSMC 15q11 therefore may be a major
      cause for male infertility.

PMID- 24078567
TI  - [Expression of BCL2L12 gene in de novo acute myeloid leukemia and its clinical
      implications].
AB  - OBJECTIVE: To explore the expression of BCL2L12 gene and its clinical
      significance for de novo acute myeloid leukemia (AML). METHODS: Real-time
      quantitative PCR (RQ-PCR) was employed to measure the expression of BCL2L12 gene
      in 134 patients with de novo AML. The results were correlated with clinical
      features of patients. RESULTS: BCL2L12 gene transcript was determined for 134 AML
      patients and 49 healthy controls, with the median levels measured 0.1029 (0.0119
      26.4090) and 0.2677 (0.0173-1.2858), respectively. There was a significant
      difference in the strength of BCL2L12 gene expression between patients and normal
      controls (P < 0.01). Those with lower BCL2L12 expression levels had a higher FLT3
      ITD mutation rate compared with those with higher levels (27% vs. 5%, P = 0.036).
      Relapsed or refractory AML patients had lower expression compared with newly
      diagnosed patients (0.0873 vs. 0.1359, P = 0.014). There was no difference in
      overall survival (OS) between patients with higher and lower expression levels.
      However, for AML patients with a normal karyotype, the OS for those with lower
      expression was significant shorter (P = 0.037). CONCLUSION: De novo AML patients
      have a lower level of BCL2L12 gene expression. AML patients with lower BCL2L12
      expression have a higher FLT3-ITD mutation rate, and most of them are relapse or
      refractory patients. In addition, among patients with a normal karyotype, those
      with a lower BCL2L12 expression have a shorter OS. Therefore, expression of the
      BCL2L12 gene may be used as a prognostic marker for AML patients with a normal
      karyotype.

PMID- 24078568
TI  - [Deletions and rearrangements of PAX5 gene in B-lineage acute lymphoblastic
      leukemia].
AB  - OBJECTIVE: To determine the frequency paired-box domain 5 (PAX5) gene alterations
      in B-lineage acute lymphoblastic leukemia (B-ALL) harboring 9p abnormalities and
      its implication for clinical prognosis. METHODS: Bacterial artificial chromosomes
      RP11-344B23 and RP11-652D9 encompassing the PAX5 gene were selected. DNA was
      extracted with conventional method and labeled with fluorescein by nicking
      transition. Fluorescence in situ hybridization (FISH) was used to determine the
      rearrangement or deletion of the PAX5 gene in B-ALL harboring chromosome 9p
      abnormalities. Clinical and laboratory features of patients were analyzed.
      RESULTS: Fifty cases were analyzed with FISH. Complete deletion was observed in
      23 patients (46%), partial deletion was observed in 2 patients (4%), and
      rearrangement was detected only in 1 case. The total frequency of abnormalities
      was 52% (26/50). No significant difference was found in clinical features of
      patients with or without PAX5 rearrangement or deletion. CONCLUSION: The
      frequency of PAX5 gene alterations in B-ALL harboring 9p abnormalities was 52%.
      However, no significant difference was found between patients with and without
      PAX5 alterations.

PMID- 24078569
TI  - [Influence of CETP gene -629C/A polymorphism on the efficacy of atorvastatin
      treatment and clinical outcome].
AB  - OBJECTIVE: To investigate cholesteryl ester transfer protein (CETP) gene
      polymorphism -629C/A among Han Chinese patients with coronary heart disease (CHD)
      in Tianjin region, and to assess the influence of genetic factors on therapeutic
      effect of atorvastatin and clinical outcome in order to provide a pharmacogenomic
      basis for personalized treatment. METHODS: From October 2010 to July 2011, 232
      patients with angiographically confirmed CHD were recruited. Polymorphism of
      position -629 of CETP gene promoter was determined with polymerase chain reaction
      - restricted fragment length polymorphism (PCR-RFLP) method. Serum level of CETP
      was determined with enzyme-linked immunosorbent assay (ELISA). Lipid level in all
      patients was determined at baseline and after 12 months of treatment with 20 mg/d
      atorvastatin. Clinical follow-up was carried out for more than a year (12-23
      months). Major adverse cardiac events including death, non-fatal infarction,
      revascularization and stroke (MACE) were recorded. A Kaplan-Meier log-rank test
      was used to compare MACE-free survival for individuals with various genotypes.
      RESULTS: The frequency of -629A allele was 0.408. Compared with CC or CA
      genotypes, individuals with AA genotype had lower CETP levels and higher high
      density lipoprotein cholesterol (HDL-C) levels, albeit without statistical
      significance (F = 0.893, P = 0.411 and F = 1.279, P = 0.282, respectively). There
      also appeared to be a negative correlation between serum HDL-C and CETP levels,
      though no statistical significance was detected (r = -0.151, P = 0.081). After 12
      months atorvastatin therapy, individuals with CC genotype had greater reduction
      of low-density lipoprotein cholesterol (LDL-C), reduced LP(a) and elevated HDL-C
      compared with CA or AA genotypes. LDL-C level has decreased by 35.41% in CC
      homozygotes, 18.84% in CA heterozygotes and 8.15% in AA homozygotes (P = 0.001).
      HDL-C level has increased by 14.37% in CC homozygotes, 10.48% in CA heterozygotes
      and 6.64% in AA homozygotes, respectively. However, above changes did not reach
      statistical significance (P = 0.470). The incidence of MACE after a mean follow
      up of (18.66 +/- 5.99) months was 7.76%, which included 2 (0.86%) deaths, 5
      (2.16%) non-fatal infarctions, 9 (3.88%) revascularizations and 2 (0.86%)
      strokes. The cumulative MACE-free survival rates were 92.4%, 85.3% and 65.0% for
      CC, CA and AA genotypes, respectively (Log-rank P = 0.444). CONCLUSION: Our
      results suggested that AA variant for the -629A allele of CETP gene had higher
      HDL-C levels and reduced CETP levels, though patients with CC genotype appeared
      to have better benefited from statin therapy with reduction in LDL-C and LP(a)
      levels. Long-term clinical prognosis was however not affected by the 3 genotypes.

PMID- 24078570
TI  - [Establishment of a hMSH2/hMSH6 protein interaction system and functional
      evaluation of hMSH2 gene missense mutations].
AB  - OBJECTIVE: To construct a hMSH2/hMSH6 protein interaction system, and to use it
      for evaluating missense mutations detected in hMSH2 gene. METHODS: Recombinant
      plasmids pGADT7-hMSH2, pGBKT7-hMSH6 and 7 recombinant pGBKT7 plasmids with
      different hMSH6 domains were constructed through genetic engineering.
      Subsequently, site-directed mutagenesis was used to construct 10 mutant pGADT7
      hMSH2 plasmids, which were transformed into yeast AH109. The growth of
      transformants was observed on a histidine-deficient culture. RESULTS: Both hMSH6
      MutSII-V and MutSIII-V could interact with hMSH2 in yeast AH109. Yeast two-hybrid
      transformants pGADT7-hMSH2/pGBKT7-hMSH6 MutSII-V were used to construct a
      hMSH2/hMSH6 protein interaction system. Compared with wild-type hMSH2, yeast two
      hybrid transformants c.505A>G, c.1168C>T, c.1255C>A, c.1261C>A could grow
      normally, c.1223A>G, c.1886A>G, c.2108C>A and c.2516A>G grew slowly, c.518T>G and
      c.1664 delA could not grow in a histidine-deficient medium in yeast AH109.
      CONCLUSION: A hMSH2/hMSH6 protein interaction system has been constructed with
      yeast two-hybrid system, which has been used for functional evaluation of hMSH2
      gene missense mutations. c.518T>G is a pathological mutation. c.1223A>G,
      c.1886A>G, c.2108C>A, c.2516A>G may in part affect the hMSH2 function. And
      c.505A>G, c.1168C>T, c.1255C>A, c.1261C>A were innocuous variants.

PMID- 24078571
TI  - [Involvement of sympathetic nervous system in the pathogenesis of hypertension].
AB  - Sustained activation of sympathetic nervous system in response to stimulation of
      a wide variety of stress factors is an independent risk factor for the
      development of essential hypertension. Adrenal hormone biosynthesis pathway as an
      important part of the sympathetic nervous system consists of hormones,
      neurotransmitters, receptors, and a variety of synthases and invertases. In this
      article, we have systematically reviewed research progresses made in elucidating
      the interactions between genes of the adrenal hormone biosynthesis pathway and
      stress factors in the pathogenesis of essential hypertension. 

PMID- 24078572
TI  - [Current status and implication of research on Bardet-Biedl syndrome].
AB  - OBJECTIVE: Bardet-Biedl syndrome (BBS) is a rare autosomal recessive disease
      initially reported by Bardet and Biedl in the 1920s. BBS is a pleiotropic and
      genetically heterogeneous disorder characterized by retinopathy, obesity,
      polydactyly, renal malformations and functional abnormalities, learning
      disabilities and hypogenitalism. BBS patients are also prone to diabetes
      mellitus, hypertension and congenital heart disease. To date, 16 BBS genes (BBS1
      BBS16) have been identified. However, the molecular etiology of BBS is not yet
      entirely clear. In this article, we have reviewed recent research on BBS and
      discussed its implications for understanding of ciliopathology.

PMID- 24078573
TI  - [Clinical and mutational features of maternal 3-methylcrotonyl coenzyme
      deficiency].
AB  - OBJECTIVE: To report on 5 patients with maternal 3-methylcrotonyl coenzyme A
      carboxylase deficiency (MCCD) and to confirm the clinical diagnosis through
      mutation analysis. METHODS: Five neonates with higher blood 3-hydroxy
      isovalerylcarnitine (C5-OH) concentration detected upon newborn screening with
      tandem mass spectrometry and their mothers were recruited. Urinary organic acids
      were analyzed with gas chromatography mass spectrometry. Gene mutation and
      protein function analysis were performed by PCR direct sequencing and PolyPhen-2
      software. RESULTS: Higher blood C5-OH concentrations (5.11-21.77 MUmol/L) and
      abnormal 3-hydroxy isovalerate and 3-methylcrotonyl glycine in urine were
      detected in the five asymptomatic mothers, who were diagnosed as benign MCCD.
      Higher C5-OH concentration was also detected in their neonates by tandem mass
      spectrometry, which had gradually decreased to normal levels in three neonates.
      Four new variations, i.e., c.ins1680A(25%), c.203C > T (p.A68V), c.572T > C
      (p.L191P) and c.639+5G > T were detected in the MCCC1 gene, in addition with 2
      mutations [c.1406G > T (p.R469L, novel variation) and c.592C > T (p.Q198X)]. The
      novel variations were predicted to have affected protein structure and function.
      CONCLUSION: For neonates with higher C5-OH concentration detected upon neonatal
      screening, their mothers should be also tested to rule out MCCD. Mutations in
      MCCC1 gene are quite common.

PMID- 24078574
TI  - [Identification of a novel PAX6 mutation in a family with congenital aniridia].
AB  - OBJECTIVE: To detect potential mutation in a Chinese family where two individuals
      were affected with hereditary congenital aniridia. METHODS: Peripheral blood
      samples were taken for genomic DNA extraction. All of the 15 exons of PAX6 gene
      were amplified with PCR. The product were purified with gel electrophoresis and
      sequenced. RESULTS: In both patients, a novel deletion mutation (c.957-958delCA)
      in exon 13 of the PAX6 gene was identified, which has produced a terminator
      codon. The same mutation was not found in healthy controls. CONCLUSION: A c.957
      958delCA mutation of PAX6 gene is probably the cause of aniridia in this Chinese
      family.

PMID- 24078575
TI  - [Analysis of PHEX gene mutation in a hypophosphatasia pedigree].
AB  - OBJECTIVE: To screen potential mutations of PHEX gene in a family featuring
      hypophosphatemic rickets in order to confirm the molecular diagnosis and
      pathogenetic mechanism. METHODS: Genomic DNA was extracted from peripheral venous
      blood samples. DNA sequence of PHEX gene was derived from UCSC database, and
      primers for its coding region were designed with Primer premier 5.0. Potential
      mutations were detected with PCR amplification and DNA sequence analysis.
      RESUTLS: A mutation was identified in intron 6 of the PHEX gene in the proband
      and his mother. CONCLUSION: The c.732+1G>T mutation underlies the
      hypophosphatemic rickets in this family.

PMID- 24078576
TI  - [Clinical and imaging features and genetic analysis of a case with adult-onset
      Krabbe disease].
AB  - OBJECTIVE: To investigate clinical and imaging features of a patient with adult
      onset Krabbe disease and to detect the underlying genetic mutations. METHODS:
      Clinical and cranial MRI features of the patient were analyzed. Pathogenesis,
      clinical manifestation, cranial MRI features and diagnostic criteria for the
      disease were discussed. RESULTS: The patient had presented asymmetric limb
      weakness and difficulty in walking. Electromyography suggested peripheral nerve
      demyelination. Cranial MRI showed increased signal intensity in white matter with
      involvement of the corticospinal tracts. Screening of GALC gene mutation has
      found the patient to be heterozygous for T1685C (Ile562Thr) and homozygous for
      A1921G (Thr641Ala), both of which were considered to be polymorphisms. In
      addition, he was heterozygous for G136T (Asp46Tyr), which had not been described
      previously. CONCLUSION: Clinical manifestations of adult-onset Krabbe disease may
      be atypical. Cranial MRI and galactocerebroside activity assay should be carried
      out for patients featuring chronic progressive corticospinal tract injury. An
      Asp46Tyr mutation probably underlies the disease in the current case.

PMID- 24078577
TI  - [Diagnosis and treatment of isolated methylmalonic acidemia].
AB  - OBJECTIVE: To explore the clinical feature, therapeutic effect and prognosis of
      isolated methylmalonic acidemia. METHODS: The clinical characteristics,
      laboratory findings, treatment and outcome of 40 patients were retrospectively
      analyzed. The main treatment was a low-protein diet supplemented with L-carnitine
      and special milk free of leucine, valine, threonine and methionine. Vitamin B12
      was also given to cobalamin responders. The patients were followed up every 1-3
      months. RESULTS: Mutations in the MUT gene were identified in 30 of 33 patients
      who had accepted DNA testing. Thirty cases were treated and followed up regularly
      for from 1 month to 8 years. Eight cases had died, 8 had developed normal
      intelligence, among whom 4 from newborn screening were asymptomatic. Psychomotor
      developmental delay and mental retardation were present in 14 cases. The
      propionylcarnitine level, ratio of propionylcarnitine/acetylcarnitine in blood,
      methylmalonic acid and methylcitric acid levels in urine have decreased
      significantly, with the median values reduced respectively from 24.15 (7.92
      81.02) MUmol/L, 1.08 (0.38-6.01), 705.34 (113.79-3078.60) and 7.71 (0.52-128.21)
      to 10.50 (3.00-30.92) MUmol/L, 0.63 (0.25-2.89), 166.23 (22.40-3322.21) and 3.96
      (0.94-119.13) (P < 0.05). CONCLUSION: The prognosis of isolated methylmalonic
      acidemia may be predicted with the enzymatic subgroup, age at onset and cobalamin
      responsiveness. Outcome is unfavorable in neonatal patients and those who were
      non-responsive to cobalamin.

PMID- 24078578
TI  - [Family-based association study of a variable number of tandem repeat
      polymorphism of DAT1 gene with Tourette syndrome in a Chinese Han population].
AB  - OBJECTIVE: To assess the association of a 40 bp variable number of tandem repeat
      (VNTR) polymorphism within 3 untranslated region of dopamine transporter gene
      (DAT1) with Tourette syndrome (TS) in a Chinese Han population. METHODS: A total
      of 160 TS patients and their parents were recruited. The VNTR polymorphism was
      detected with polymerase chain reaction-VNTR analysis, and its association with
      TS and its subtypes were assessed through a family-based association study
      comprising transmission disequilibrium test (TDT) and haplotype relative risk
      (HRR) analysis. RESULTS: The repeat numbers at the DAT1 40 bp locus were 11, 10,
      9, 7.5 and 7 among the patients and their parents, with the most common type
      being a 10-repeat allele. No significant association was detected between the
      polymorphism and TS (TDT: X 2 = 0.472, df = 1, P = 0.583; HRR: X 2 = 0.313, P =
      0.576, OR = 0.855, 95%CI: 0.493-1.481). CONCLUSION: Our data suggested that the
      VNTR polymorphism of DAT1 gene is not associated with susceptibility to TS in
      Chinese Han population. However, our results are to be validated in larger sets
      of patients collected from other populations.

PMID- 24078579
TI  - [Prenatal diagnosis of a case with X-linked spondyloepiphyseal dysplasia tarda].
AB  - OBJECTIVE: To analyze TRAPPC2 gene mutation in a family with X-linked
      spondyloepiphyseal dysplasia tarda and to provide genetic counseling and prenatal
      diagnosis. METHODS: All of 4 exons of the TRAPPC2 gene and their flanking
      sequences in the proband and her father were analyzed with polymerase chain
      reaction and direct DNA sequencing. Genomic DNA of the probands' fetus was
      extracted from amniotic fluid sampled at 18th gestational week. Gender of the
      fetus was determined by the presence of SRY gene. The sequence of fetal TRAPPC2
      gene was also analyzed. RESULTS: A c.209G>A mutation was identified in exon 4 of
      the TRAPPC2 gene in the proband and her father. The fetus of was determined to be
      a male and also have carried the c.209G>A mutation. CONCLUSION: A c.209G>A
      mutation of TRAPPC2 exon 4 probably underlies the clinical manifestations in this
      family. The proband is a carrier, and her fetus is a male carrying the same
      mutation. Prenatal diagnosis is an effective method for the prevention of the
      disease.

PMID- 24078580
TI  - [Association of chemokines and their receptors genes polymorphisms with risk of
      myocardial infarction].
AB  - OBJECTIVE: To assess the association of variations in chemokines (CCL5, CCL2),
      chemokine receptor (CCR5 and CCR2) genes with susceptibility to myocardial
      infarction (MI) through a case-control study. METHODS: Genotypes of patients with
      MI (n = 634) were compared with those of controls (n = 601). Genetic
      polymorphisms of CCL5 rs2107538 (-403G > A), CCL2 rs1024611 (-2518A > G), CCR5
      rs333 ( delta 32 ins or del) and CCR2 rs1799864 (190G > A) of 1235 individuals
      were determined with polymerase chain reaction and restriction fragment length
      polymorphism (PCR-RFLP). Particular genotypes were confirmed with DNA sequencing.
      RESULTS: No subject was found to carry the CCR5 - delta 32 allele. No association
      was found between CCL2 rs1024611 and CCR2 rs1799864 polymorphisms and MI. For
      CCL5 rs2107538 polymorphism, the A allele has occurred at a higher frequency in
      MI patients than controls, and its AA genotype has been associated with a
      significantly increased risk of MI independent of conventional risk factors (OR =
      3.346, 95%CI = 1.938-5.775, P < 0.01, AA vs. GG). Further analysis indicated that
      MI patients had significantly more A-403 - A-2518 haplotype (CCL5 -403G > A and
      CCL2 -2518A > G, 21.8% vs. 26.6%, OR = 1.229, 95%CI = 1.012-1.493, P = 0.038) and
      AA or AA genotype (CCL5 -403G > A - CCL2 -2518A > G, 5.0% vs. 12.1%, OR = 3.245,
      95%CI = 1.780-5.914, P < 0.01). CONCLUSION: Although our data dose not support an
      association between CCL2 rs1024611, CCR2 rs1799864 and CCR5 rs333 polymorphisms
      and MI, genetic variation in CCL5 gene may still be a useful marker for assessing
      susceptibility to MI in ethnic Han Chinese population.

PMID- 24078581
TI  - [Hereditary motor neuropathy - a family with 9 cases].

PMID- 24078582
TI  - [Clinical and cytogenetic analysis of 45,X/46,XY individuals].
AB  - OBJECTIVE: To analyze main clinical manifestations and cytogenetic
      characteristics of patients with a 45,X/46,XY karyotype. METHODS: G-banding
      karyotype analysis was carried out. PCR was performed to detect azoospermia
      factor (AZF) microdeletion in adult male patients and sex-determining region on Y
      chromosome (SRY) gene in all patients. Clinical phenotype and genetic
      characteristics were summarized. RESULTS: Among the 9 individuals with
      45,X/46,XY, there have been 7 males and 2 females. Six out of the 7 males have
      manifested primary infertility, which included 5 with azoospermia, 1 with
      oligospermia, and 1 with hypospadia. Three of the 6 infertile patients were found
      to have AZF microdeletions. Two females showed typical Turner syndrome. All of
      the 9 cases were SRY-positive. CONCLUSION: The 45,X/46,XY karyotype may result in
      a range of phenotypes. No correlation has been found between clinical
      manifestations and proportion of mosaicism cells for their peripheral blood
      karyotypes. As phenotypically normal male patients may produce sperm, infertile
      patients should undergo further examination at the molecular level.

PMID- 24078583
TI  - [Prenatal diagnosis and clinical counseling for fetal chromosomal reciprocal
      translocations].
AB  - OBJECTIVE: To analyze the clinical effect of fetal chromosomal reciprocal
      translocation in order to optimize procedures for prenatal diagnosis and clinical
      counseling. METHODS: Conventional G-banding karyotype analysis was performed on
      7901 amniotic fluid samples. For fetuses found to have carried a reciprocal
      translocation, karyotypes of their parents were checked. Fetuses with de novo
      translocations also underwent microarray analysis to exclude small deletions, and
      were subjected to prenatal ultrasound monitoring till birth and one year follow
      up. Those with de novo translocations were followed till 3 years old. RESULTS: A
      total of 24 fetal reciprocal translocations have been identified, which gave a
      detection rate of 0.30%. Analysis of parental karyotypes has found reciprocal
      translocations in 17 cases, including 9 maternal and 8 paternal cases. The
      remaining 4 were of de novo mutations, for which parental examination was refused
      in three cases. For fetuses with inherited translocations, prenatal ultrasound
      monitoring and follow-up results were all normal. For those with de novo
      translocations, although gene chip analysis has failed to detect copy number
      variations (CNVs), prenatal ultrasound and follow-up results had found three with
      abnormal outcome. These included 1 case with reciprocal translocation involving
      the X chromosome and an autosome. CONCLUSION: For prenatally detected reciprocal
      chromosome translocations, parental origin should be traced. Gene chip analysis
      can help to exclude small deletions and duplications. However, ultrasound
      monitoring and follow-up after birth are equally important. Based on
      comprehensive analysis of the results of combined testing, accurate counseling
      can be provided.

PMID- 24078584
TI  - [Application of ROC curve for evaluation of the effect of prenatal screening
      during second trimester of pregnancy].
AB  - OBJECTIVE: To develop a method for evaluating the feasibility of prenatal
      screening using local median value and determining the cut-off value. METHODS:
      With receiver operating characteristic curve (ROC) analysis, results of second
      trimester prenatal screening calculated by a local median value in a new model
      and the built-in median value in 2T software were compared. The cut-off value was
      set by serial analysis of true and false positive rates and other relevant data.
      RESULTS: The ROC curve has accurately estimated the difference in the screening
      efficacy between a local median value and that embedded in the 2T model, and
      established a reasonable cut-off value for the laboratory based on false positive
      rate and detection rate. CONCLUSION: The method of ROC curve can be used to
      evaluate the performance of local median value in prenatal screening and to test
      the rationality of cut-off value established in the laboratory. As the result, a
      better cut-off value may be derived.

PMID- 24078585
TI  - [DNA extraction and sex determination for human teeth dated 3000 years ago
      unearthed in Xi'an].
AB  - OBJECTIVE: To extracted DNA from ancient human teeth dated 3000 years ago
      unearthed in Xi'an and determine the genders for the individuals. METHODS: Thirty
      five ancient human teeth were studied. A 'Reverse-root-canal' technique and a
      Chelex-100 solution were used to extract the DNA. Specific primers for Amelogenin
      gene were designed for PCR amplification. RESULTS: Genomic DNA was successfully
      extracted from 30 samples, for which 8 were determined to be males and 22 were
      females. CONCLUSION: The 'Reverse-root-canal' technique may be used for
      extracting DNA from ancient human teeth. Genetics method can supplement physical
      anthropology for determination of sex for ancient samples.

PMID- 24078586
TI  - [Analysis of allele dropout at TH01 locus in paternity testing].
AB  - OBJECTIVE: To analyze allele dropout at TH01 locus in paternity testing in order
      to determine the accurate genotype. METHODS: To use a two STR loci genotyping
      system to verify an abnormal genotype for the TH01 locus with PCR using specific
      primers, cloning and DNA sequencing. RESULTS: A rare allele at TH01 locus named
      5.2, which was undetectable with PowerPlex 21 system, was detected with an
      Identifiler system. CONCLUSION: Genetic variations may result in rare alleles and
      loci loss. To avoid misjudgment, laboratories should have a variety of methods
      for detecting loci loss.

PMID- 24078587
TI  - [Analysis of polymorphisms of mitochondrial DNA in 3 ethnic groups of Guizhou].
AB  - OBJECTIVE: To analyze the population genetics characteristics of mitochondrial
      DNA (mtDNA) in Gelao, Mulao, Maonan ethnic groups from Guizhou. METHODS:
      Minisequenceing and restriction fragment length polymorphism (RFLP) were used to
      analyze 12 single nucleotide polymorphism (SNPs) of mitochondrial DNA in the 3
      ethnic groups. RESULTS: A total of 30 haplotypes were detected in 156 samples.
      The distribution of H1, H23 had differed between Mulao, Maonan and Gelao,
      respectively, and so did M7 among the three groups. The difference was
      statistically significant (P < 0.05). Mulao, Maonan had respectively differed
      from Gelao and the difference was also statistically significant (P < 0.05).
      CONCLUSION: There was a great similarity in the distribution of haplotypes of the
      mtDNA among the three ethnic groups, except for some difference in the
      distribution of certain haplotypes.

PMID- 24078590
TI  - N-acylated alanine methyl esters (NAMEs) from Roseovarius tolerans, structural
      analogs of quorum-sensing autoinducers, N-acylhomoserine lactones.
AB  - The Roseobacter clade is one of the most important bacteria group living in the
      ocean. Liquid cultures of Roseovarius tolerans EL 164 were investigated for the
      production of autoinducers such as N-acylhomoserine lactones (AHLs) and other
      secondary metabolites. The XAD extracts were analyzed by GC/MS. Two AHLs, Z7-C14
      : 1-homoserine lactone (HSL) and C15 : 1-HSL, were identified. Additionally, the
      extract contained five compounds with molecular-ion peaks at m/z 104, 145, and
      158, thus exhibiting mass spectra similar to those of AHLs with corresponding
      peaks at m/z 102, 143, and 156. Isolation of the main compound by column
      chromatography, NMR analysis, dimethyl disulfide derivatization for the
      determination of the location of the C?C bond and finally synthesis of the
      compound with the proposed structure confirmed the compound to be (Z)-N-(hexadec
      9-enoyl)alanine methyl ester. Four additional minor compounds were identified as
      C14 : 0-, C15 : 0-, C16 : 0-, and C17 : 1-N-acylated alanine methyl esters
      (NAMEs). All NAMEs have not been described from natural sources before. A BLASTp
      search showed the presence of AHL-producing luxI genes, but no homologous genes
      potentially responsible for the structurally closely related NAMEs were found.
      The involvement of the NAMEs in chemical communication processes of the bacteria
      is discussed. 

PMID- 24078591
TI  - Gates and binding pockets for nitric oxide with cytochrome c', according to
      molecular dynamics.
AB  - Random-acceleration molecular-dynamics (RAMD) simulations with models of
      homodimeric 6-ligated distal-NO and 5-ligated proximal-NO cytochrome c'
      complexes, in TIP3 H2 O, showed two distinct, non-intercommunicating worlds. In
      the framework of a long cavity formed by four protein helices with heme at one
      extremity, NO was observed to follow different pathways with the two complexes to
      reach the solvent. With the 6-ligated complex, NO was observed to progress by
      exploiting protein internal channels created by thermal fluctuations, and be
      temporarily trapped into binding pockets before reaching the preferred gate at
      the heme end of the cavity. In contrast, with the 5-ligated complex, NO was
      observed to surface the solvent-exposed helix 7, up to a gate at the other
      extremity of the protein, only occasionally finding an earlier, direct way out
      toward the solvent. That only bulk NO gets involved in forming the 5-ligated
      proximal-NO complex is in agreement with previous experimental observations,
      while the occurrence of binding pockets suggests that also reservoir NO might
      play a role with the distal-NO complex. 

PMID- 24078592
TI  - Chrotacumines E and F, two new chromone-alkaloid analogs from Dysoxylum
      acutangulum (Meliaceae) leaves.
AB  - A chemical investigation of the alkaloidal fraction of Dysoxylum acutangulum
      leaves led to the isolation and characterization of two new chromone alkaloid
      analogs named chrotacumines E and F (1 and 2, resp.). Structure elucidation of 1
      and 2 was achieved by spectroscopic analyses, including 2D-NMR. Both of these
      alkaloids exhibited modest activities as tyrosinase inhibitors with 29.2 and
      25.8% inhibition at 100 MUg/ml, respectively. 

PMID- 24078593
TI  - Aggregation-induced emission of 1,8-naphthalimide-casein micelle: investigation
      by synchronous spectrographic method.
AB  - A novel 1,8-naphthalimide probe 1, bearing two acetic-acid moieties was
      synthesized. The acetic-acid groups, docked into the sub-domains of casein
      micelle and bound with tryptophan residues, and the 1,8-naphthalimide chromophore
      adsorbed on the surface of casein micelle, forming a supermolecule, 1-casein
      micelle, which exhibited the aggregation-induced synchronous emission (AISE)
      characters. The effect of pH on the intensity of supermolecule was investigated,
      and the result indicated that the emission enhancement was mainly due to the 1,8
      naphthalimide chromophore aggregated onto the casein micelle. Based on AISE, a
      novel casein quantification method was developed, which exhibited a good linear
      range of 0.05-10.0 MUg ml(-1) and 0.07-9.5 MUg ml(-1) with the detection limits
      of 2.8 and 3.0 ng ml(-1) . The effects of metal ions and pH on the system of 1
      casein micelle were investigated. The proposed method was applied to determine
      casein in milk samples, and the results were in good agreement with the result of
      the Biuret method.

PMID- 24078594
TI  - cis-clerodane diterpenes from the liverwort Scapania ciliata.
AB  - Chemical investigation of the Chinese liverwort Scapania ciliata led to the
      isolation of four new cis-clerodane lactones, named ciliatolides A-D (1-4,
      resp.), among which compound 1 was found to be a tetranorclerodanoid. Their
      structures were determined by extensive analysis of spectroscopic data, and, in
      the case of compound 1, together with a single-crystal X-ray diffraction
      analysis. The absolute configurations were established by analysis of the CD
      spectra and by quantum-chemical CD calculations. The cytotoxicities of compounds
      1-4 were preliminarily tested against the PC3 and MCF-7 cell lines. 

PMID- 24078595
TI  - Cycloartanes from the gum resin of Gardenia gummifera L.f.
AB  - The gum resin exuding from the leaf buds of Gardenia gummifera was investigated.
      Eight new cycloartane triterpenes, 1-6, 8, and 10, together with two known
      triterpenes, 25-hydroxycycloart-23-en-3-one (7) and cycloartenone (9), were
      isolated and identified by extensive NMR spectroscopy. For cycloartenone (9),
      full NMR assignments are given as these data were not available in the
      literature. Eight compounds possess a C(3)=O group, two are 3,4-secocycloartanes
      bearing a free C(3)OOH group; in one of the cycloartanes, gummiferartane-9 (10),
      ring A occurs as a seven-membered lactone.

PMID- 24078596
TI  - Diterpenoids from Acanthopanax brachypus Harms.
AB  - Four diterpenoids, including two new ones, namely noracanthopanin A (1) and
      acanthopanolide B (2), and two known ones, ent-pimara-9(11),15-dien-19-oic acid
      (3) and ent-kaur-16-en-19-oic acid (4), were isolated from the stem bark of
      Acanthopanax brachypus Harms. Their structures were elucidated by physicochemical
      and spectroscopic analyses. Compound 1 and 2 exhibited moderate cytotoxicities
      against HO-8910 cells with IC50 values of 65.21+/-0.23 and 31.43+/-1.01 MUg/ml,
      respectively, and 2 showed selective weak cytotoxicity against SMMC-7721 cells
      (IC50 89.67+/-2.54 MUg/ml). 

PMID- 24078597
TI  - Triterpenoids from the stem bark of Melia toosendan and determination of their
      absolute configurations at C(24).
AB  - Six new triterpenoids, meliasenins S-X (1-6, resp.), were isolated from the stem
      bark of Melia toosendan. Their structures were elucidated by mass spectrometry,
      NMR experiments, and comparison with the known compounds. Particularly, the
      absolute configuration at C(24) in new compounds was determined through their CD
      spectra of the [Pr(FOD)3 ] complex (fod=1,1,1,2,2,3,3,7,7,7-decafluoroheptane-4,6
      dione) in CCl4 , as well as by using Mosher's method. 

PMID- 24078598
TI  - The volatile profiles of a rare apple (Malus domestica Borkh.) honey: shikimic
      acid-pathway derivatives, terpenes, and others.
AB  - The volatile profiles of rare Malus domestica Borkh. honey were investigated for
      the first time. Two representative samples from Poland (sample I) and Spain
      (sample II) were selected by pollen analysis (44-45% of Malus spp. pollen) and
      investigated by GC/FID/MS after headspace solid-phase microextraction (HS-SPME)
      and ultrasonic solvent extraction (USE). The apple honey is characterized by high
      percentage of shikimic acid-pathway derivatives, as well as terpenes,
      norisoprenoids, and some other compounds such as coumaran and methyl 1H-indole-3
      acetate. The main compounds of the honey headspace were (sample I; sample II):
      benzaldehyde (9.4%; 32.1%), benzyl alcohol (0.3%; 14.4%), hotrienol (26.0%,
      6.2%), and lilac aldehyde isomers (26.3%; 1.7%), but only Spanish sample
      contained car-2-en-4-one (10.2%). CH2 Cl2 and pentane/Et2 O 1 : 2 (v/v) were used
      for USE. The most relevant compounds identified in the extracts were:
      benzaldehyde (0.9-3.9%), benzoic acid (2.0-11.2%), terpendiol I (0.3-7.4%),
      coumaran (0.0-2.8%), 2-phenylacetic acid (2.0-26.4%), methyl syringate (3.9
      13.1%), vomifoliol (5.0-31.8%), and methyl 1H-indole-3-acetate (1.9-10.2%). Apple
      honey contained also benzyl alcohol, 2-phenylethanol, (E)-cinnamaldehyde, (E)
      cinnamyl alcohol, eugenol, vanillin, and linalool that have been found previously
      in apple flowers, thus disclosing similarity of both volatile profiles. 

PMID- 24078599
TI  - Variability of the root essential oils of Seseli rigidum Waldst. & Kit.
      (Apiaceae) from different populations in Serbia.
AB  - The chemical compositions of the essential oils of seven natural populations of
      Seseli rigidum were analyzed. The essential-oil yield ranged from 0.16 to 2.09%.
      Analysis of variance (ANOVA) revealed that there were no statistically
      significant differences in the mean essential-oil yields between the populations,
      and no significant influence of the climate or soil type on the oil yield was
      observed. In all 67 analyzed samples, the polyacetylene falcarinol was the main
      compound, followed by octanal, methyl linoleate, alpha-muurolene, 3
      butylphthalide, falcarinone, muurola-4,10(14)-dien-1beta-ol, beta
      sesquiphellandrene, salvial-4(14)-en-1-one, delta-amorphene, spathulenol, and
      isospathulenol. The principal component analysis (PCA), the canonical
      discriminant analysis (CDA), and the cluster analysis (CA) revealed
      differentiation between the populations based on the climate. Three groups of
      populations were formed; the first group was composed of samples growing in
      regions with a humid climate, with oils having high falcarinol and low
      sesquiterpene contents, and the second and third groups comprised samples exposed
      to semi-arid climate, with oils characterized by a lower falcarinol and higher
      alpha-muurolene, delta-amorphene, beta-sesquiphellandrene, and salvial-4(14)-en-1
      one contents. The semi-arid populations were divided into two groups, which were
      distinguished based on the oil contents of sesquiterpenes, falcarinone, and 3
      butylphthalide. On the other hand, no clear separation between populations based
      on the different soil types could be observed. 

PMID- 24078600
TI  - Chemical composition of essential oils and aromatic waters from different Italian
      Anthemis maritima populations.
AB  - The chemical composition of the essential oils and aromatic waters isolated from
      six Italian Anthemis maritima populations was determined by GC-FID and GC/MS
      analyses. In total, 122 and 100 chemical compounds were identified in the
      essential oils and the aromatic waters, respectively. The main compound classes
      represented in the oils were monoterpene hydrocarbons, oxygenated monoterpenes,
      sesquiterpene hydrocarbons, oxygenated sesquiterpenes, and terpene esters.
      Multivariate chemometric techniques such as cluster analysis (CA) and principal
      coordinate analysis (PCO) were used to classify the samples according to the
      geographical origin. Statistical analysis allowed the attribution of the analyzed
      populations to different chemotype groups. 

PMID- 24078601
TI  - Odor qualities and thresholds of physiological metabolites of 1,8-cineole as an
      example for structure-activity relationships considering chirality aspects.
AB  - The present study aimed at analyzing the odor properties of a group of
      physiological human metabolites of the odorant 1,8-cineole: 2,3-dehydro-,
      alpha2,3-epoxy-, alpha/beta2-hydroxy-, alpha3-hydroxy-, 4-hydroxy-, 7-hydroxy-, 9
      hydroxy-, 2-oxo-, and 3-oxo-1,8-cineole. These metabolites constitute a group of
      structurally closely related molecules, which differ mainly in nature and
      position of O-containing functional groups. They thus offer the possibility to
      correlate odor properties with molecular structure, i.e., to establish structure
      odor relationships of compounds that are biologically generated from a potent
      odorant as parent substance. Generally, the metabolites preserved the eucalyptus
      like odor quality of 1,8-cineole but showed additional odor notes such as sweet,
      citrus-like, plastic-like, earthy, musty, and faecal, which made them
      distinguishable. The individual enantiomers of chiral molecules also exhibited
      different odors. With the exception of 2,3-dehydro-1,8-cineole, all metabolites
      showed a highly decreased odor threshold in comparison to 1,8-cineole. The
      determination of odor qualities and odor thresholds was accomplished by gas
      chromatography/olfactometry (GC/O) on achiral and chiral GC capillaries. The
      results were correlated with common theories on structure-odor relationships.

PMID- 24078602
TI  - Increases in both acute and chronic temperature potentiate tocotrienol
      concentrations in wild barley at 'Evolution Canyon'.
AB  - Biosynthesis of tocols (vitamin E isoforms) is linked to response to temperature
      in plants. 'Evolution Canyon', an ecogeographical microcosm extending over an
      average of 200 meters (range 100-400) wide area in the Carmel Mountains of
      northern Israel, has been suggested as a model for studying global warming. Both
      domestic (Hordeum vulgare) and wild (Hordeum spontaneum) barley compared with
      wheat, oat, corn, rice, and rye show high tocotrienol/tocopherol ratios.
      Therefore, we hypothesized that tocol distribution might change in response to
      global warming. alpha-, beta-, gamma-, and delta-tocopherol, and alpha-, beta-,
      gamma-, and delta-tocotrienol concentrations were measured in wild barley (H.
      spontaneum) seeds harvested from the xeric (African) and mesic (European) slopes
      of Evolution Canyon over a six-year period from 2005-2011. Additionally, we
      examined seeds from areas contiguous to and distant from the part of the Canyon
      severely burned during the Carmel Fire of December 2010. Increased alpha
      tocotrienol (p<0.01) was correlated with 1) temperature increases, 2) to the
      hotter 'African' slope in contrast to the cooler 'European' slope, and 3) to
      propinquity to the fire. The study illustrates the role of alpha-tocotrienol in
      both chronic and acute temperature adaptation in wild barley and suggests future
      research into thermoregulatory mechanisms in plants. 

PMID- 24078603
TI  - Metabolic fate of depsides and alkaloid constituents in aqueous extracts from
      Mercurialis perennis L. during fermentation.
AB  - Dog's mercury (Mercurialis perennis L.) is an old medicinal plant, nowadays used
      in complementary medicine. Aqueous fermented extracts of the plant are being
      mainly applied in remedies to treat external inflammations, but a thorough
      phytochemical characterization is still lacking. Therefore, the conversion of
      characteristic compound classes from M. perennis extracts during fermentation and
      storage was investigated. The microbial transformation of the two main depsides
      phaselic acid (=(2R)-O-[(E)-caffeoyl]malic acid; 1) and mercurialis acid (=(2R)
      [(E)-caffeoyloxy]glutaric acid; 2) was monitored by HPLC-DAD. The degradation
      followed a second-order kinetic, and the calculated half-life periods of both
      constituents were 67 and 30 months, respectively. Several depside metabolites
      were detected by GC/MS in AcOEt extracts as (t) BuMe2 Si (TBDMS) derivatives
      after derivatization, mainly dihydrocinnamic acids. Moreover, numerous alpha
      hydroxy acids were found, allegedly as degradation products from amino acids or
      peptides. The microbial alteration of the main alkaloid hermidin was also
      examined. After three days of fermentation, three novel N-metabolites were formed
      and thoroughly assigned in CH2 Cl2 extracts as a mixture of 3-ethylhermidin, 3
      ethylhermidin quinone, and (E/Z)-3-ethylidenehermidin by GC/MS and NMR methods,
      as well as by means of total synthesis. A mechanism for the formation of these N
      metabolites starting from dimeric hermidin oxidation products is proposed. The
      obtained results reveal the complex pathways plant constituents may undergo
      during the fermentation of the extracts. 

PMID- 24078604
TI  - Ethnochemistry and human rights.

PMID- 24078605
TI  - Animates are better remembered than inanimates: further evidence from word and
      picture stimuli.
AB  - In three experiments, we showed that animate entities are remembered better than
      inanimate entities. Experiment 1 revealed better recall for words denoting
      animate than inanimate items. Experiment 2 replicated this finding with the use
      of pictures. In Experiment 3, we found better recognition for animate than for
      inanimate words. Importantly, we also found a higher recall rate of "remember"
      than of "know" responses for animates, whereas the recall rates were similar for
      the two types of responses for inanimate items. This finding suggests that
      animacy enhances not only the quantity but also the quality of memory traces,
      through the recall of contextual details of previous experiences (i.e., episodic
      memory). Finally, in Experiment 4, we tested whether the animacy effect was due
      to animate items being richer in terms of sensory features than inanimate items.
      The findings provide further evidence for the functionalist view of memory
      championed by Nairne and coworkers (Nairne, 2010; Nairne & Pandeirada, Cognitive
      Psychology, 61 :1-22, 2010a, 2010b).

PMID- 24078609
TI  - Exopolysaccharides from Sinorhizobium meliloti can protect against H2O2-dependent
      damage.
AB  - Sinorhizobium meliloti requires exopolysaccharides in order to form a successful
      nitrogen-fixing symbiosis with Medicago species. Additionally, during early
      stages of symbiosis, S. meliloti is presented with an oxidative burst that must
      be overcome. Levels of production of the exopolysaccharides succinoglycan (EPS-I)
      and galactoglucan (EPS-II) were found to correlate positively with survival in
      hydrogen peroxide (H2O2). H2O2 damage is dependent on the presence of iron and is
      mitigated when EPS-I and EPS-II mutants are cocultured with cells expressing
      either exopolysaccharide. Purified EPS-I is able to decrease in vitro levels of
      H2O2, and this activity is specific to the symbiotically active low-molecular
      weight form of EPS-I. This suggests a potential protective function of
      exopolysaccharides against H2O2 during early symbiosis. 

PMID- 24078610
TI  - Functional characterization of SbmA, a bacterial inner membrane transporter
      required for importing the antimicrobial peptide Bac7(1-35).
AB  - SbmA is an inner membrane protein of Gram-negative bacteria that is involved in
      the internalization of glycopeptides and prokaryotic and eukaryotic antimicrobial
      peptides, as well as of peptide nucleic acid (PNA) oligomers. The SbmA homolog
      BacA is required for the development of Sinorhizobium meliloti bacteroids within
      plant cells and favors chronic infections with Brucella abortus and Mycobacterium
      tuberculosis in mice. Here, we investigated functional features of SbmA/BacA
      using the proline-rich antimicrobial peptide Bac7(1-35) as a substrate. Circular
      dichroism and affinity chromatography studies were used to investigate the
      ability of SbmA to bind the peptide, and a whole-cell transport assay with
      fluorescently labeled peptide allowed the determination of transport kinetic
      parameters with a calculated Km value of 6.95 +/- 0.89 MUM peptide and a Vmax of
      53.91 +/- 3.17 nmol/min/mg SbmA. Use of a bacterial two-hybrid system coupled to
      SEC-MALLS (size exclusion chromatography coupled with multiangle laser light
      scattering) analyses established that SbmA is a homodimer in the membrane, and
      treatment of the cells with arsenate or ionophores indicated that the peptide
      transport mediated by SbmA is driven by the electrochemical gradient. Overall,
      these results shed light on the SbmA-mediated internalization of peptide
      substrates and suggest that the transport of an unknown substrate(s) represents
      the function of this protein. 

PMID- 24078611
TI  - Functional and structural study of the dimeric inner membrane protein SbmA.
AB  - SbmA protein has been proposed as a dimeric secondary transporter. The protein is
      involved in the transport of microcins B17 and J25, bleomycin, proline-rich
      antimicrobial peptides, antisense peptide phosphorodiamidate morpholino
      oligomers, and peptide nucleic acids into the Escherichia coli cytoplasm. The
      sbmA homologue is found in a variety of bacteria, though the physiological role
      of the protein is hitherto unknown. In this work, we carried out a functional and
      structural analysis to determine which amino acids are critical for the transport
      properties of SbmA. We created a set of 15 site-directed sbmA mutants in which
      single conserved amino acids were replaced by glycine residues. Our work
      demonstrated that strains carrying the site-directed mutants V102G, F219G, and
      E276G had a null phenotype for SbmA transport functions. In contrast, strains
      carrying the single point mutants W19G, W53G, F60G, S69G, N155G, R190, L233G,
      A344G, T255G, N308G, and R385G showed transport capacities indistinguishable from
      those of strains harboring a wild-type sbmA. The strain carrying the Y116G mutant
      exhibited mixed phenotypic characteristics. We also demonstrated that those sbmA
      mutants with severely impaired transport capacity showed a dominant negative
      phenotype. Electron microscopy data and in silico three-dimensional (3D) homology
      modeling support the idea that SbmA forms a homodimeric complex, closely
      resembling the membrane-spanning region of the ATP-binding cassette transporter
      family. Direct mapping of the sbmA single point mutants on the protein surface
      allowed us to explain the observed phenotypic differences in transport ability. 

PMID- 24078612
TI  - Phenotypic profiling of Mycobacterium tuberculosis EspA point mutants reveals
      that blockage of ESAT-6 and CFP-10 secretion in vitro does not always correlate
      with attenuation of virulence.
AB  - The EspA protein of Mycobacterium tuberculosis is essential for the type VII ESX
      1 protein secretion apparatus, which delivers the principal virulence factors
      ESAT-6 and CFP-10. In this study, site-directed mutagenesis of EspA was performed
      to elucidate its influence on the ESX-1 system. Replacing Trp(55) (W55) or
      Gly(57) (G57) residues in the putative W-X-G motif of EspA with arginines
      impaired ESAT-6 and CFP-10 secretion in vitro and attenuated M. tuberculosis.
      Replacing the Phe(50) (F50) and Lys(62) (K62) residues, which flank the W-X-G
      motif, with arginine and alanine, respectively, destabilized EspA, abolished ESAT
      6 and CFP-10 secretion in vitro, and attenuated M. tuberculosis. Likewise,
      replacing the Phe(5) (F5) and Lys(41) (K41) residues with arginine and alanine,
      respectively, also destabilized EspA and blocked ESAT-6 and CFP-10 secretion in
      vitro. However, these two particular mutations did not attenuate M. tuberculosis
      in cellular models of infection or during acute infection in mice. We have thus
      identified amino acid residues in EspA that are important for facilitating ESAT-6
      and CFP-10 secretion and virulence. However, our data also indicate for the first
      time that blockage of M. tuberculosis ESAT-6 and CFP-10 secretion in vitro and
      attenuation are mutually exclusive. 

PMID- 24078613
TI  - The sll1951 gene encodes the surface layer protein of Synechocystis sp. strain
      PCC 6803.
AB  - Sll1951 is the surface layer (S-layer) protein of the cyanobacterium
      Synechocystis sp. strain PCC 6803. This large, hemolysin-like protein was found
      in the supernatant of a strain that was deficient in S-layer attachment. An
      sll1951 deletion mutation was introduced into Synechocystis and was easily
      segregated to homozygosity under laboratory conditions. By thin-section and
      negative-stain transmission electron microscopy, a ~30-nm-wide S-layer lattice
      covering the cell surface was readily visible in wild-type cells but was absent
      in the Deltasll1951 strain. Instead, the Deltasll1951 strain displayed a smooth
      lipopolysaccharide surface as its most peripheral layer. In the presence of
      chaotropic agents, the wild type released a large (>150-kDa) protein into the
      medium that was identified as Sll1951 by mass spectrometry of trypsin fragments;
      this protein was missing in the Deltasll1951 strain. In addition, Sll1951 was
      prominent in crude extracts of the wild type, indicating that it is an abundant
      protein. The carotenoid composition of the cell wall fraction of the Deltasll1951
      strain was similar to that of the wild type, suggesting that the S-layer does not
      contribute to carotenoid binding. Although the photoautotrophic growth rate of
      the Deltasll1951 strain was similar to that of the wild-type strain, the
      viability of the Deltasll1951 strain was reduced upon exposure to lysozyme
      treatment and hypo-osmotic stress, indicating a contribution of the S-layer to
      the integrity of the Synechocystis cell wall. This work identifies the S-layer
      protein in Synechocystis and shows that, at least under laboratory conditions,
      this very abundant, large protein has a supportive but not a critical role in the
      function of the cyanobacterium.

PMID- 24078614
TI  - Tetracycline-related transcriptional regulation of the CTnDOT mobilization
      region.
AB  - CTnDOT is a 65-kb conjugative transposon (CTn) in Bacteroides spp. that confers
      resistance to the antibiotics erythromycin and tetracycline (Tc). Conjugative
      transfer of CTnDOT is regulated upon exposure of cells to Tc. In the absence of
      Tc, no transfer is detectable; however, a cascade of regulatory events results in
      the conjugative transfer of CTnDOT upon Tc induction. Previous studies addressing
      regulation of CTnDOT conjugative transfer focused primarily on the 13-kb transfer
      (tra) operon, which encodes the proteins required for assembly of the mating
      apparatus. We report here that the mob operon that encodes the relaxase and
      coupling proteins required for mobilization of CTnDOT are regulated at the
      transcriptional level upon Tc induction. The Xis2d and Exc excision proteins are
      required for the upregulation of mob transcription upon Tc induction, and yet a
      deletion of xis2c has no effect. We also show preliminary evidence suggesting
      that the integrase, IntDOT, may play a regulatory role, as pLYL72 transfer is not
      detectable when intDOT is provided in trans. 

PMID- 24078617
TI  - Opportunities for genome-wide selection for pig breeding in developing countries.
AB  - Genetic improvement of exotic and indigenous pigs in tropical developing
      countries is desired. Implementations of traditional selection methods on
      tropical pig populations are limited by lack of data recording and analysis
      infrastructure. Genome-wide selection (GS) provides an approach for achieving
      faster genetic progress without developing a pedigree recording system. The
      implications of GS on long-term gain and inbreeding should be studied before
      actual implementation, especially where low linkage disequilibrium (LD) is
      anticipated in the target population. A simulation case study of this option was
      performed on the basis of the available 60,000 SNP panel for porcine genome.
      Computer simulation was used to explore the effects of various selection methods,
      trait heritability, and different breeding programs when applying GS. Genomic
      predictions were based on the ridge regression method. Genome-wide selection
      performed better than BLUP and phenotypic selection methods by increasing genetic
      gain and maintaining genetic variation while lowering inbreeding, especially for
      traits with low heritability. Indigenous pig populations with low LD can be
      improved by using GS if high-density marker panels are available. The combination
      of GS with repeated backcrossing of crossbreds to exotic pigs in developing
      countries promises to rapidly improve the genetic merit of the commercial
      population. Application of this novel method on a real population will need to be
      performed to validate these results. 

PMID- 24078616
TI  - High-throughput screens for eEF-2 kinase.
AB  - eEF-2 kinase is a potential therapeutic target for breast cancer, gliomas, and
      depression. No potent inhibitors of eEF-2K have been reported, and thus
      development of high-throughput assay systems may expedite the process. Two high
      throughput assays are described for eEF-2K using recombinant, tag-free enzyme
      purified from bacteria. The first is a fluorescence-based assay that uses the
      phosphorylation of a Sox-based peptide substrate by eEF-2K, which results in a 5
      fold increase in fluorescence emission, allowing for continuous monitoring of the
      kinase activity. The second is a luminescence-based assay that produces a
      luminescence signal, which correlates with the amount of adenosine triphosphate
      remaining in the kinase reaction. Both assays have been optimized and
      miniaturized for a 384-well plate format and validated in screens. In conclusion,
      we demonstrated that a traditional radiolabeled assay can be readily transferred
      to universal spectroscopic assays that are robust and will facilitate high
      throughput screening of larger size libraries for the identification of small
      molecule inhibitors and significantly contribute to the development of therapies
      for targeting eEF2K. 

PMID- 24078615
TI  - ICESluvan, a 94-kilobase mosaic integrative conjugative element conferring
      interspecies transfer of VanB-type glycopeptide resistance, a novel bacitracin
      resistance locus, and a toxin-antitoxin stabilization system.
AB  - A 94-kb integrative conjugative element (ICESluvan) transferable to Enterococcus
      faecium and Enterococcus faecalis from an animal isolate of Streptococcus
      lutetiensis consists of a mosaic of genetic fragments from different Gram
      positive bacteria. A variant of ICESluvan was confirmed in S. lutetiensis from a
      patient. A complete Tn5382/Tn1549 with a vanB2 operon is integrated into a
      streptococcal ICESde3396-like region harboring a putative bacteriophage exclusion
      system, a putative agglutinin receptor precursor, and key components of a type IV
      secretion system. Moreover, ICESluvan encodes a putative MobC family mobilization
      protein and a relaxase and, thus, in total has all genetic components essential
      for conjugative transfer. A 9-kb element within Tn5382/Tn1549 encodes, among
      others, putative proteins similar to the TnpX site-specific recombinase in
      Faecalibacterium and VanZ in Paenibacillus, which may contribute to the detected
      low-level teicoplanin resistance. Furthermore, ICESluvan encodes a novel
      bacitracin resistance locus that is associated with reduced susceptibility to
      bacitracin when transferred to E. faecium. The expression of a streptococcal
      pezAT toxin-antitoxin-encoding operon of ICESluvan in S. lutetiensis, E. faecium,
      and E. faecalis was confirmed by reverse transcription (RT)-PCR, indicating an
      active toxin-antitoxin system which may contribute to stabilizing ICESluvan
      within new hosts. Junction PCR and DNA sequencing confirmed that ICESluvan
      excised to form a circular intermediate in S. lutetiensis, E. faecalis, and E.
      faecium. Transfer between E. faecalis cells was observed in the presence of
      helper plasmid pIP964. Sequence analysis of the original S. lutetiensis donor and
      enterococcal transconjugants showed that ICESluvan integrates in a site-specific
      manner into the C-terminal end of the chromosomal tRNA methyltransferase gene
      rumA. 

PMID- 24078618
TI  - Accuracy of predicting genomic breeding values for residual feed intake in Angus
      and Charolais beef cattle.
AB  - In beef cattle, phenotypic data that are difficult and/or costly to measure, such
      as feed efficiency, and DNA marker genotypes are usually available on a small
      number of animals of different breeds or populations. To achieve a maximal
      accuracy of genomic prediction using the phenotype and genotype data, strategies
      for forming a training population to predict genomic breeding values (GEBV) of
      the selection candidates need to be evaluated. In this study, we examined the
      accuracy of predicting GEBV for residual feed intake (RFI) based on 522 Angus and
      395 Charolais steers genotyped on SNP with the Illumina Bovine SNP50 Beadchip for
      3 training population forming strategies: within breed, across breed, and by
      pooling data from the 2 breeds (i.e., combined). Two other scenarios with the
      training and validation data split by birth year and by sire family within a
      breed were also investigated to assess the impact of genetic relationships on the
      accuracy of genomic prediction. Three statistical methods including the best
      linear unbiased prediction with the relationship matrix defined based on the
      pedigree (PBLUP), based on the SNP genotypes (GBLUP), and a Bayesian method
      (BayesB) were used to predict the GEBV. The results showed that the accuracy of
      the GEBV prediction was the highest when the prediction was within breed and when
      the validation population had greater genetic relationships with the training
      population, with a maximum of 0.58 for Angus and 0.64 for Charolais. The within
      breed prediction accuracies dropped to 0.29 and 0.38, respectively, when the
      validation populations had a minimal pedigree link with the training population.
      When the training population of a different breed was used to predict the GEBV of
      the validation population, that is, across-breed genomic prediction, the
      accuracies were further reduced to 0.10 to 0.22, depending on the prediction
      method used. Pooling data from the 2 breeds to form the training population
      resulted in accuracies increased to 0.31 and 0.43, respectively, for the Angus
      and Charolais validation populations. The results suggested that the genetic
      relationship of selection candidates with the training population has a greater
      impact on the accuracy of GEBV using the Illumina Bovine SNP50 Beadchip. Pooling
      data from different breeds to form the training population will improve the
      accuracy of across breed genomic prediction for RFI in beef cattle. 

PMID- 24078619
TI  - Individual physical characteristics of neonatal piglets affect preweaning
      survival of piglets born in a noncrated system.
AB  - The aim of this study was to investigate the effects of individual physical
      characteristics on preweaning survival and growth of piglets born in a noncrate
      system. Data were collected from 3,402 neonatal piglets from 203 Landrace *
      Yorkshire sows housed in noncrate pens in a commercial Danish sow herd. Piglets
      were categorized into groups according to their survivability: surviving to
      weaning (SURV), stillborn (STILL), or dead between birth and weaning (DBW), which
      was subdivided into dead d 0 to 1 after farrowing (DEAD1) or dead d 2 to 26 after
      farrowing (DEAD26). Linear models were used to determine which physical
      characteristics affected survivability and growth of piglets. Results showed that
      characteristics related to the individual piglets had a greater degree of
      explanatory power in relation to survival than variables related to the sow.
      Survival of piglets increased if piglets were females (P < 0.001), had a greater
      body mass index (P < 0.001), and were born to sows of parity 3 or more (P =
      0.017). Piglets with a greater birth weight were more likely to survive (P <
      0.001), but birth weight was inferior to body mass index in explaining
      differences between SURV and DBW. Piglets that died 2 to 26 d after birth had a
      lower birth weight (P < 0.001), were born to sows of parity 1 or 2 (P = 0.014),
      and were born after a shorter gestation (P = 0.011) compared with SURV. Piglets
      that died on d 0 to 1 after birth had a lower body mass index (P < 0.001),
      displayed a greater degree of growth restriction (P = 0.004), and were born in
      large litters (P = 0.005). The gender of the piglets affected survivability at
      both d 0 to 1 (P < 0.001) and d 2 to 26 (P < 0.001). Piglets in DEAD1 differed
      from STILL by having a shorter crown to rump length (P < 0.001), a birth weight
      that deviated more from the mean weight of the litter (P = 0.001), and being more
      likely to be born before d 116 of gestation (P = 0.008). The only physical
      characteristic that was important for growth performance in the suckling period
      was birth weight (P < 0.001), yet using only birth weight as an indicator for
      survivability was too simplistic. The results of this study emphasize that
      individual characteristics of neonatal piglets could serve as indicators of
      survivability of piglets born in noncrate systems; however, the results suggest
      that the importance of characteristics differed in different periods of the
      preweaning period. 

PMID- 24078620
TI  - Discrepancies in cancer incidence and mortality and its relationship to health
      expenditure in the 27 European Union member states.
AB  - BACKGROUND: The European Union (EU) is a confederation of 27 member states, the
      institutions of which work according to negotiated decisions. The EU has
      implemented similar legislation and a common market, and has adopted the same
      currency in most of its member states. Although financing health systems is a
      responsibility of the national governments, the EU has enacted the Charter of
      Fundamental Rights to standardize public health policies. However, for historical
      reasons, health policy and health expenditure is not uniform across the 27 EU
      member states (EU-27). MATERIAL AND METHODS: We hypothesized that increased
      health expenditure would be associated with better cancer outcome and that this
      would be most apparent in breast cancer, because of the availability of effective
      screening methods and treatments. Using publically available data from the World
      Health Organization, the International Monetary Fund, and the World Bank, we
      assessed associations between cancer indicators and wealth and health indicators.
      To do so, we constructed scatter plots and used the Spearman's rank correlation
      coefficient. RESULTS: A marked difference in wealth and health expenditure
      indicators was observed between Eastern and Western European countries, with
      Western European being the higher. Higher wealth and higher health expenditures
      were associated both with increased cancer incidence and decreased cancer
      mortality. In breast cancer, the association with incidence was stronger. We
      created mortality/incidence ratios and observed that the more spent on health,
      the fewer the deaths after a cancer diagnosis. CONCLUSION: Despite the
      initiatives to standardize public health policies of the EU-27, health
      expenditure continues to be higher in Western European countries and this is
      associated with better cancer outcome in these countries.

PMID- 24078621
TI  - Editor's letter.

PMID- 24078622
TI  - Norovirus-like virus outbreak at a correctional facility in Haliburton Kawartha
      Pine Ridge District Health Unit, March to April 2008.
AB  - In March 2008, an enteric outbreak was reported from a correctional facility in
      Central East Ontario to the Haliburton, Kawartha, Pine Ridge District Health
      Unit. The clinical and epidemiological data were compatible with the presence of
      norovirus in this enteric outbreak. This report summarizes the outbreak
      investigation conducted and the various public health measures undertaken through
      a coordinated response by the facility health care and correctional staff and
      local and provincial health authorities to contain the infection within the
      facility. Correctional facilities present unique challenges to the implementation
      of infection control measures, and the investigators eventually recommended that
      the facility be closed to transfers and new admissions until the outbreak was
      brought under control. 

PMID- 24078623
TI  - Health status, sexual and drug risk, and psychosocial factors relevant to
      postrelease planning for HIV+ prisoners.
AB  - The prevalence of HIV infection among male prison inmates is significantly higher
      than in the U.S. population. Adequate planning to ensure continued medication
      adherence and continuity of care after release is important for this population.
      This study describes the prerelease characteristics of 162 incarcerated HIV
      positive men (40 from jails and 122 from prisons). The results include a
      demographic description of the sample and the participants' sexual risk
      behaviors, substance use, health status and HIV medication adherence, health care
      utilization, mental health, and family and social support. The results highlight
      a potentially high level of need for services and low levels of support and
      social connectedness. Postrelease planning should include support for improving
      HIV medication adherence as well as reducing both sexual and injection drug
      related transmission risk for these individuals. 

PMID- 24078624
TI  - Policies and practices in the delivery of HIV services in correctional agencies
      and facilities: results from a multisite survey.
AB  - HIV risk is disproportionately high among incarcerated individuals. Corrections
      agencies have been slow to implement evidence-based guidelines and interventions
      for HIV prevention, testing, and treatment. The emerging field of implementation
      science focuses on organizational interventions to facilitate adoption and
      implementation of evidence-based practices. A survey of correctional agency
      partners from the Criminal Justice Drug Abuse Treatment Studies (CJ-DATS)
      revealed that HIV policies and practices in prevention, detection, and medical
      care varied widely, with some corrections agencies and facilities closely
      matching national guidelines and/or implementing evidence-based interventions.
      Others, principally attributed to limited resources, had numerous gaps in
      delivery of best HIV service practices. A brief overview is provided of a new CJ
      DATS cooperative research protocol, informed by the survey findings, to test an
      organization-level intervention to reduce HIV service delivery gaps in
      corrections. 

PMID- 24078627
TI  - Azadirone, a limonoid tetranortriterpene, induces death receptors and sensitizes
      human cancer cells to tumor necrosis factor-related apoptosis-inducing ligand
      (TRAIL) through a p53 protein-independent mechanism: evidence for the role of the
      ROS-ERK-CHOP-death receptor pathway.
AB  - Although tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) has
      shown efficacy in a phase 2 clinical trial, development of resistance to TRAIL by
      tumor cells is a major roadblock. We investigated whether azadirone, a limonoidal
      tetranortriterpene, can sensitize human tumor cells to TRAIL. Results indicate
      that azadirone sensitized cancer cells to TRAIL. The limonoid induced expression
      of death receptor (DR) 5 and DR4 but did not affect expression of decoy receptors
      in cancer cells. The induction of DRs was mediated through activation of ERK and
      through up-regulation of a transcription factor CCAAT enhancer-binding protein
      homologous protein (CHOP) as silencing of these signaling molecules abrogated the
      effect of azadirone. These effects of azadirone were cancer cell-specific. The
      CHOP binding site on the DR5 gene was required for induction of DR5 by azadirone.
      Up-regulation of DRs was mediated through the generation of reactive oxygen
      species (ROS) as ROS scavengers reduced the effect of azadirone on ERK
      activation, CHOP up-regulation, DR induction, and TRAIL sensitization. The
      induction of DRs by this limonoid was independent of p53, but sensitization to
      TRAIL was p53-dependent. The limonoid down-regulated the expression of cell
      survival proteins and up-regulated the proapoptotic proteins. The combination of
      azadirone with TRAIL was found to be additive at concentrations lower than IC50,
      whereas at higher concentrations, the combination was synergistic. Overall, this
      study indicates that azadirone can sensitize cancer cells to TRAIL through ROS
      ERK-CHOP-mediated up-regulation of DR5 and DR4 signaling, down-regulation of cell
      survival proteins, and up-regulation of proapoptotic proteins. 

PMID- 24078628
TI  - Sequential proteolytic processing of the triggering receptor expressed on myeloid
      cells-2 (TREM2) protein by ectodomain shedding and gamma-secretase-dependent
      intramembranous cleavage.
AB  - Triggering receptor expressed on myeloid cells-2 (TREM2) and its signaling
      adaptor protein TYROBP/DAP12 play important roles in signal transduction in
      dendritic cells, osteoclasts, tissue macrophages, and microglia. Recently, TREM2
      variants have been shown to be linked to late onset Alzheimer disease. Here, we
      demonstrate that TREM2 undergoes sequential proteolytic processing by ectodomain
      shedding and intramembrane proteolysis. The C-terminal fragment (CTF) of TREM2
      generated by ectodomain shedding is cleaved by gamma-secretase. Importantly,
      pharmacologic and genetic gamma-secretase inhibition resulted in accumulation of
      TREM2 CTF at the plasma membrane that also interacts with the signaling adaptor
      protein DAP12. Thus, the accumulated TREM2 CTF thereby might limit the
      interaction of DAP12 with the functional full-length receptor, resulting in
      decreased DAP12 phosphorylation and impaired metabolism of phosphatidylinositol
      4,5-bisphosphate. Together, these data demonstrate gamma-secretase-mediated
      intramembranous proteolysis of TREM2 and functionally link two Alzheimer disease
      associated proteins in one signaling pathway. 

PMID- 24078629
TI  - Early B-cell factor 1 regulates the expansion of B-cell progenitors in a dose
      dependent manner.
AB  - Transcription factor doses are of importance for normal and malignant B
      lymphocyte development; however, the understanding of underlying mechanisms and
      functional consequences of reduced transcription factor levels is limited. We
      have analyzed progenitor and B-lineage compartments in mice carrying heterozygote
      mutations in the E2a, Ebf1, or Pax5 gene. Although lymphoid progenitors from Ebf1
      or Pax5 heterozygote mice were specified and lineage-restricted in a manner
      comparable with Wt progenitors, this process was severely impaired in E2a
      heterozygote mutant mice. This defect was not significantly enhanced upon
      combined deletion of E2a with Ebf1 or Pax5. Analysis of the pre-B-cell
      compartment in Ebf1 heterozygote mice revealed a reduction in cell numbers. These
      cells expressed Pax5 and other B-lineage-associated genes, and global gene
      expression analysis suggested that the reduction of the pre-B-cell compartment
      was a result of impaired pre-B-cell expansion. This idea was supported by a
      reduction in IL2Ralpha-expressing late pre-B-cells as well as by cell cycle
      analysis and by the finding that the complexity of the VDJ rearrangement patterns
      was comparable in Wt and Ebf1(+/-) pre-B-cells, although the number of
      progenitors was reduced. Heterozygote deletion of Ebf1 resulted in impaired
      response to IL7 in vitro and reduced expression levels of pre-BCR on the cell
      surface, providing possible explanations for the observed stage-specific
      reduction in cellular expansion. Thus, transcription factor doses are critical
      for specification as well as expansion of B-lymphoid progenitors, providing
      increased insight into the molecular regulation of B-cell development. 

PMID- 24078630
TI  - LMBD1 protein serves as a specific adaptor for insulin receptor internalization.
AB  - Energy homeostasis is crucial for maintaining normally functioning cells;
      disturbances in this balance often cause various diseases. The limb region 1
      (LMBR1) domain containing 1 gene (lmbrd1) encodes the LMBD1 protein that
      possesses 9 putative transmembrane domains. LMBD1 has been suggested to be
      involved in the lysosome in aiding the export of cobalamin. In this study, we
      determined that LMBD1 plays a regulatory role in the plasma membrane. A micro
      positron emission tomography analysis showed that a single-allele knock-out of
      lmbrd1 increased the (18)F-fluorodeoxyglucose uptake in murine hearts. In
      addition, the knockdown of lmbrd1 resulted in an up-regulated signaling of the
      insulin receptor (IR) and its downstream signaling molecule, Akt. Confocal and
      live total internal reflection fluorescence microscopy showed that LMBD1 co
      localized and co-internalized with clathrin and the IR, but not with the
      transferrin receptor. The results of the mutation analysis and phenotypic rescue
      experiments indicate that LMBD1 interacts with adaptor protein-2 and is involved
      in the unique clathrin-mediated endocytosis of the IR. LMBD1 selectively
      interacts with the IR. The knockdown of lmbrd1 attenuated IR endocytosis,
      resulting in the perturbation of the IR recycling pathway and consequential
      enhancement of the IR signaling cascade. In summary, LMBD1 plays an imperative
      role in mediating and regulating the endocytosis of the IR. 

PMID- 24078631
TI  - An immunomodulating motif of the HIV-1 fusion protein is chirality-independent:
      implications for its mode of action.
AB  - An immunosuppressive motif was recently found within the HIV-1 gp41 fusion
      protein (termed immunosuppressive loop-associated determinant core motif (ISLAD
      CM)). Peptides containing the motif interact with the T-cell receptor (TCR)
      complex; however, the mechanism by which the motif exerts its immunosuppressive
      activity is yet to be determined. Recent studies showed that interactions between
      protein domains in the membrane milieu are not always sterically controlled.
      Therefore, we utilized the unique membrane leniency toward association between D-
      and L-stereoisomers to investigate the detailed mechanism by which ISLAD CM
      inhibits T-cell activation. We show that a D-enantiomer of ISLAD CM (termed ISLAD
      D-CM) inhibited the proliferation of murine myelin oligodendrocyte glycoprotein
      (MOG)-(35-55)-specific line T-cells to the same extent as the l-motif form.
      Moreover, the D- and L-forms preferentially bound spleen-derived T-cells over B
      cells by 13-fold. Furthermore, both forms of ISLAD CM co-localized with the TCR
      on activated T-cells and interacted with the transmembrane domain of the TCR.
      FRET experiments revealed the importance of basic residues for the interaction
      between ISLAD CM forms and the TCR transmembrane domain. Ex vivo studies
      demonstrated that ISLAD D-CM administration inhibited the proliferation (72%) and
      proinflammatory cytokine secretion of pathogenic MOG(35-55)-specific T-cells.
      This study provides insights into the immunosuppressive mechanism of gp41 and
      demonstrates that chirality-independent interactions in the membrane can take
      place in diverse biological systems. Apart from HIV pathogenesis, the D-peptide
      reported herein may serve as a potential tool for treating T-cell-mediated
      pathologies.

PMID- 24078632
TI  - The extracellular chaperone haptoglobin prevents serum fatty acid-promoted
      amyloid fibril formation of beta2-microglobulin, resistance to lysosomal
      degradation, and cytotoxicity.
AB  - Fibril formation of beta2-microglobulin and associated inflammation occur in
      patients on long term dialysis. We show that the plasma protein haptoglobin
      prevents the fatty acid-promoted de novo fibril formation of beta2-microglobulin
      even at substoichiometric concentration. The fibrils are cytotoxic, and
      haptoglobin abolishes the cytotoxicity by preventing fibril formation.
      Haptoglobin does not alleviate the cytotoxicity of preformed fibrils. Fibrillar
      beta2-microglobulin is resistant to lysosomal degradation. However, the species
      of beta2-microglobulin populated in the presence of haptoglobin is susceptible to
      degradation. We observed that haptoglobin interacts with oligomeric prefibrillar
      species of beta2-microglobulin but not with monomeric or fibrillar beta2
      microglobulin that may underlie the molecular mechanism. 1,1'-Bis(4
      anilino)naphthalene-5,5'-disulfonic acid cross-linking to haptoglobin
      significantly compromises its chaperone activity, suggesting the involvement of
      hydrophobic surfaces. Haptoglobin is an acute phase protein whose level increases
      severalfold during inflammation, where local acidosis can occur. Our data show
      that haptoglobin prevents fibril formation of beta2-microglobulin under
      conditions of physiological acidosis (between pH 5.5 and 6.5) but with relatively
      decreased efficiency. However, compromise in its chaperone activity under these
      conditions is more than compensated by its increased level of expression under
      inflammation. Erythrolysis is known to release hemoglobin into the plasma.
      Haptoglobin forms a 1:1 (mol/mol) complex with hemoglobin. This complex, like
      haptoglobin, interacts with the prefibrillar species of beta2-microglobulin,
      preventing its fibril formation and the associated cytotoxicity and resistance to
      intracellular degradation. Thus, our study demonstrates that haptoglobin is a
      potential extracellular chaperone for beta2-microglobulin even in moderately
      acidic conditions relevant during inflammation, with promising therapeutic
      implications in beta2-microglobulin amyloid-related diseases. 

PMID- 24078633
TI  - A mechanistic basis for the co-evolution of chicken tapasin and major
      histocompatibility complex class I (MHC I) proteins.
AB  - MHC class I molecules display peptides at the cell surface to cytotoxic T cells.
      The co-factor tapasin functions to ensure that MHC I becomes loaded with high
      affinity peptides. In most mammals, the tapasin gene appears to have little
      sequence diversity and few alleles and is located distal to several classical MHC
      I loci, so tapasin appears to function in a universal way to assist MHC I peptide
      loading. In contrast, the chicken tapasin gene is tightly linked to the single
      dominantly expressed MHC I locus and is highly polymorphic and moderately diverse
      in sequence. Therefore, tapasin-assisted loading of MHC I in chickens may occur
      in a haplotype-specific way, via the co-evolution of chicken tapasin and MHC I.
      Here we demonstrate a mechanistic basis for this co-evolution, revealing
      differences in the ability of two chicken MHC I alleles to bind and release
      peptides in the presence or absence of tapasin, where, as in mammals, efficient
      self-loading is negatively correlated with tapasin-assisted loading. We found
      that a polymorphic residue in the MHC I alpha3 domain thought to bind tapasin
      influenced both tapasin function and intrinsic peptide binding properties.
      Differences were also evident between the MHC alleles in their interactions with
      tapasin. Last, we show that a mismatched combination of tapasin and MHC alleles
      exhibit significantly impaired MHC I maturation in vivo and that polymorphic MHC
      residues thought to contact tapasin influence maturation efficiency.
      Collectively, this supports the possibility that tapasin and BF2 proteins have co
      evolved, resulting in allele-specific peptide loading in vivo. 

PMID- 24078634
TI  - Characterization of GdFFD, a D-amino acid-containing neuropeptide that functions
      as an extrinsic modulator of the Aplysia feeding circuit.
AB  - During eukaryotic translation, peptides/proteins are created using L-amino acids.
      However, a D-amino acid-containing peptide (DAACP) can be produced through post
      translational modification via an isomerase enzyme. General approaches to
      identify novel DAACPs and investigate their function, particularly in specific
      neural circuits, are lacking. This is primarily due to the difficulty in
      characterizing this modification and due to the limited information on neural
      circuits in most species. We describe a multipronged approach to overcome these
      limitations using the sea slug Aplysia californica. Based on bioinformatics and
      homology to known DAACPs in the land snail Achatina fulica, we targeted two
      predicted peptides in Aplysia, GFFD, similar to achatin-I (GdFAD versus GFAD,
      where dF stands for D-phenylalanine), and YAEFLa, identical to fulyal (YdAEFLa
      versus YAEFLa), using stereoselective analytical methods, i.e. MALDI MS
      fragmentation analysis and LC-MS/MS. Although YAEFLa in Aplysia was detected only
      in an all L-form, we found that both GFFD and GdFFD were present in the Aplysia
      CNS. In situ hybridization and immunolabeling of GFFD/GdFFD-positive neurons and
      fibers suggested that GFFD/GdFFD might act as an extrinsic modulator of the
      feeding circuit. Consistent with this hypothesis, we found that GdFFD induced
      robust activity in the feeding circuit and elicited egestive motor patterns. In
      contrast, the peptide consisting of all L-amino acids, GFFD, was not bioactive.
      Our data indicate that the modification of an L-amino acid-containing
      neuropeptide to a DAACP is essential for peptide bioactivity in a motor circuit,
      and thus it provides a functional significance to this modification.

PMID- 24078637
TI  - Baroreflex sensitivity after kidney transplantation: arterial or neural
      improvement?

PMID- 24078635
TI  - The RclR protein is a reactive chlorine-specific transcription factor in
      Escherichia coli.
AB  - Reactive chlorine species (RCS) such as hypochlorous acid are powerful
      antimicrobial oxidants. Used extensively for disinfection in household and
      industrial settings (i.e. as bleach), RCS are also naturally generated in high
      quantities during the innate immune response. Bacterial responses to RCS are
      complex and differ substantially from the well characterized responses to other
      physiologically relevant oxidants, like peroxide or superoxide. Several RCS
      sensitive transcription factors have been identified in bacteria, but most of
      them respond to multiple stressors whose damaging effects overlap with those of
      RCS, including reactive oxygen species and electrophiles. We have now used in
      vivo genetic and in vitro biochemical methods to identify and demonstrate that
      Escherichia coli RclR (formerly YkgD) is a redox-regulated transcriptional
      activator of the AraC family, whose highly conserved cysteine residues are
      specifically sensitive to oxidation by RCS. Oxidation of these cysteines leads to
      strong, highly specific activation of expression of genes required for survival
      of RCS stress. These results demonstrate the existence of a widely conserved
      bacterial regulon devoted specifically to RCS resistance. 

PMID- 24078636
TI  - Nuclear ALG-2 protein interacts with Ca2+ homeostasis endoplasmic reticulum
      protein (CHERP) Ca2+-dependently and participates in regulation of alternative
      splicing of inositol trisphosphate receptor type 1 (IP3R1) pre-mRNA.
AB  - The intracellular Ca(2+) signaling pathway is important for the control of broad
      cellular processes from fertilization to cell death. ALG-2 is a Ca(2+)-binding
      protein that contains five serially repeated EF-hand motifs and interacts with
      various proteins in a Ca(2+)-dependent manner. Although ALG-2 is present both in
      the cytoplasm and in the nucleus, little is known about its nuclear function.
      Ca(2+) homeostasis endoplasmic reticulum protein (CHERP) was first identified as
      an endoplasmic reticulum protein that regulates intracellular Ca(2+) mobilization
      in human cells, but recent proteomics data suggest an association between CHERP
      and spliceosomes. Here, we report that CHERP, containing a Pro-rich region and a
      phosphorylated Ser/Arg-rich RS-like domain, is a novel Ca(2+)-dependent ALG-2
      interactive target in the nucleus. Immunofluorescence microscopic analysis
      revealed localization of CHERP to the nucleoplasm with prominent accumulation at
      nuclear speckles, which are the sites of storage and modification for pre-mRNA
      splicing factors. Live cell time-lapse imaging showed that nuclear ALG-2 was
      recruited to the CHERP-localizing speckles upon Ca(2+) mobilization. Results of
      co-immunoprecipitation assays revealed binding of CHERP to a phosphorylated form
      of RNA polymerase II. Knockdown of CHERP or ALG-2 in HT1080 cells resulted in
      generation of alternatively spliced isoforms of the inositol 1,4,5-trisphosphate
      receptor 1 (IP3R1) pre-mRNA that included exons 41 and 42 in addition to the
      major isoform lacking exons 40-42. Furthermore, binding between CHERP and IP3R1
      RNA was detected by an RNA immunoprecipitation assay using a polyclonal antibody
      against CHERP. These results indicate that CHERP and ALG-2 participate in
      regulation of alternative splicing of IP3R1 pre-mRNA and provide new insights
      into post-transcriptional regulation of splicing variants in Ca(2+) signaling
      pathways. 

PMID- 24078638
TI  - Dialysis-induced segmental wall motion abnormalities, post-dialysis fatigue and
      cardiovascular mortality: the new Bermuda triangle?

PMID- 24078639
TI  - Time-course morphological and functional disorders of the kidney induced by long
      term high-fat diet intake in female rats.
AB  - BACKGROUND: Evidence is emerging that highlights the far-reaching consequences of
      a high-fat diet (HFD) on kidney morphology and function disorders. METHODS: The
      present study was performed on 3-, 5-, 7- and 9-week-old HFD female rats compared
      with the appropriate gender and age-matched animals. We evaluated the kidney
      expression of angiotensin type II receptor and fibrotic and epithelial-to
      mesenchymal transition (EMT) markers, by immunoblotting and immunohistochemical
      and histological techniques, in parallel with kidney function. RESULTS: In the
      current study, the time-course HFD-treated group showed, by immunoblotting and
      immunohistochemical analysis, an early time-course increase in the expression of
      transforming growth factor beta-1 (TGFbeta-1) in the entire kidney of HFD-treated
      rats, compared with that observed in the control group. Simultaneously, the study
      shows a transient increase in the expression of ZEB2 in the HFD whole kidney
      accompanied by a fall in the E-cadherin expression and increased collagen and
      fibronectin deposition. A pronounced decrease in fractional urinary sodium
      excretion was also demonstrated in the long-term HFD-treated rats. The decreased
      FENa(+) was accompanied by a fall in FEPNa(+) and FEPPNa(+), which occurred in
      association with significantly decreased CCr and, certainly on the sodium
      filtered load. The reduction in the glomerular filtration rate (GFR) occurred in
      parallel to proteinuria and glomerular desmin overexpression. CONCLUSIONS: The
      results of the current study suggest that podocyte injury in parallel with
      observed proteinuria and evidence of EMT transformation are associated with long
      term loss of kidney function and renal sodium and water retention.

PMID- 24078640
TI  - Kruppel-like factor 5 associates with melamine-cyanurate crystal-induced
      nephritis in rats.
AB  - BACKGROUND: Melamine and cyanuric acid (M/CA), when orally administered together
      to rats, can induce crystal formation within renal tubules and cause acute kidney
      injury. METHODS: To investigate the pathomechanism of crystal-induced nephritis,
      melamine and/or cyanuric acid were administered to 3-week-old (young) and 8-week
      old (adult) rats, respectively. RESULTS: Crystal formation, blood urea nitrogen
      elevation, tubular cell injury and macrophage infiltration were noted in rats fed
      with M/CA, but not in rats fed with vehicle, melamine or CA alone. These
      parameters were significantly higher in young rats than those in adult rats fed
      with M/CA 200 mg/kg body weight (BW) for 3 days. Kruppel-like factor 5 (KLF5) was
      expressed on distal tubule cells, especially when crystals deposited within the
      lumens. Both mRNA and protein levels were higher in young rats than those in
      adult rats fed with M/CA (200 mg/kg BW). KLF5 expression has been shown to
      modulate renal tissue cytokine production, and we found that proinflammatory
      cytokines like monocyte chemoattractant protein-1 and interlukin-6 were increased
      in kidney tissues of young rats fed with M/CA for 3 days. In contrast, interlukin
      10, an anti-inflammatory cytokine, was upregulated in kidneys of adult rats fed
      with M/CA for 3 days. CONCLUSIONS: Crystals are prone to deposition in distal
      tubules of young rats fed with M/CA. M/CA Crystal-related nephritis might be
      induced by the KLF5 expression, which modulated macrophage recruitment and
      proinflammatory cytokine production, subsequently leading to renal tubular injury
      and interstitial inflammation.

PMID- 24078641
TI  - Inhibition of hyaluronan is protective against renal ischaemia-reperfusion
      injury.
AB  - BACKGROUND: Ischaemia-reperfusion injury (IRI) to the kidney is a complex
      pathophysiological process that leads to acute renal failure and chronic
      dysfunction in renal allografts. It was previously demonstrated that during IRI,
      hyaluronan (HA) accumulates in the cortical and external medullary interstitium
      along with an increased expression of its main receptor, CD44, on inflammatory
      and tubular cells. The HA-CD44 pair may be involved in persistent post-ischaemic
      inflammation. Thus, we sought to determine the role of HA in the pathophysiology
      of ischaemia-reperfusion (IR) by preventing its accumulation in post-ischaemic
      kidney. METHODS: C57BL/6 mice received a diet containing 4-methylumbelliferone (4
      MU), a potent HA synthesis inhibitor. At the end of the treatment, unilateral
      renal IR was induced and mice were euthanized 48 h or 30 days post-IR. RESULTS: 4
      MU treatment for 14 weeks reduced the plasma HA level and intra-renal HA content
      at 48 h post-IR, as well as CD44 expression, creatininemia and histopathological
      lesions. Moreover, inflammation was significantly attenuated and proliferation
      was reduced in animals treated with 4-MU. In addition, 4-MU-treated mice had a
      significantly reduced expression of alpha-SMA and collagen types I and III, i.e.
      less renal fibrosis, 30 days after IR compared with untreated mice. CONCLUSION:
      Our results demonstrate that HA plays a significant role in the pathogenesis of
      IRI, perhaps in part through reduced expression of CD44. The suppression of HA
      accumulation during IR may protect renal function against ischaemic insults.

PMID- 24078642
TI  - Variation in intravenous iron use internationally and over time: the Dialysis
      Outcomes and Practice Patterns Study (DOPPS).
AB  - BACKGROUND: To examine patterns of intravenous (IV) iron use across 12 countries
      from 1999 to 2011. METHODS: Trends in iron use are described among 32 192
      hemodialysis (HD) patients in the Dialysis Outcomes and Practice Patterns Study.
      Adjusted associations of IV iron dose with serum ferritin and transferrin
      saturation (TSAT) values were also studied. RESULTS: IV iron was administered to
      50% of patients over 4 months in 1999, increasing to 71% during 2009-11, with
      increasing use in most countries. Among patients receiving IV iron, the mean
      monthly dose increased from 232 +/- 167 to 281 +/- 211 mg. Most countries used 3
      to 4 doses/month, but Canada used about 2 doses/month, Italy increased from 3 to
      almost 6 doses/month and Germany used 5 to 6 doses/month. The USA and most
      European countries predominantly used iron sucrose and sodium ferric gluconate. A
      significant use of iron dextran was limited to Canada and France; iron
      polymaltose was used in Australia and New Zealand; and Japan used ferric oxide
      saccharate, chondroitin polysulfate iron complex and cideferron. Ferritin values
      rose in most countries: 22% of patients had >= 800 ng/mL in the recent years of
      study. TSAT levels increased to a lesser degree over time. Japan had much lower
      IV iron dosing and ferritin levels, but similar TSAT levels. In adjusted
      analyses, serum ferritin and TSAT levels increased signifcantly by 14 ng/mL and
      0.16%, respectively, for every 100 mg/month higher mean monthly iron dose.
      CONCLUSIONS: IV iron prescription patterns varied between countries and changed
      over time from 1999 to 2011. IV iron use and dose increased in most countries,
      with notable increases in ferritin but not TSAT levels. With rising cumulative IV
      iron doses, studies of the effects of changing IV iron dosing and other anemia
      management practices on clinical outcomes should be a high priority.

PMID- 24078643
TI  - Impact of targeting Kt instead of Kt/V.
AB  - BACKGROUND: Patients must receive an adequate dialysis dose in each hemodialysis
      (HD) session. Ionic dialysance (ID) enables the dialysis dose to be monitored in
      each session. The aim of this study was to compare the achievement of Kt versus
      eKt/V values and to analyse the main impediments to reaching the dialysis dose.
      METHODS: Of 5316 patients from 54 Fresenius Medical Care centers in Spain
      undergoing their usual HD regime, 3275 received ID and were included in the
      study. RESULTS: The minimum prescribed dose of eKt/V was reached in 91.2% of the
      patients, while the minimum recommended dose of Kt was reached in only 66.8%.
      Patients not receiving the minimum Kt dose were older, had spent 7 months less on
      dialysis, had a dialysis duration of 6 min less, had 5.7 kg more of body weight
      and Qb was 47 mL/min lower. The target Kt was not reached by 62% of patients with
      catheters and by 37% of women. With each quintile increase of body weight, eKt/V
      decreased and Kt increased. Of patients with a body weight >80 kg, 1.4%, mostly
      men, reached the target Kt but not prescribed eKt/V. CONCLUSIONS: The impact of
      monitoring the dose with Kt instead of Kt/V is that identifies 25.8% of patients
      who did not reach the minimum Kt while achieving Kt/V. The main impediments to
      achieving an adequate dialysis dose were catheter use, female sex, advanced age,
      greater body weight, shorter dialysis time and lower Qb.

PMID- 24078644
TI  - Technique survival in home haemodialysis: a composite success rate and its risk
      predictors in a prospective longitudinal cohort from a tertiary renal network
      programme.
AB  - BACKGROUND: Resurgence of interest in home haemodialysis (HHD) is, in part, due
      to emerging evidence of the benefits of extended HD regimens, which are most
      feasibly provided in the home setting. Although specific HHD therapy established
      at home such as nocturnal HD (NHD) has been reported from individual programmes,
      little is known about overall HHD success. METHODS: The study included 166
      patients who were accepted in the Manchester (UK) HHD training programme through
      liberal selection criteria. All patients were followed up prospectively until a
      switch to alternative modality, to include 4528 patient-months of follow-up and
      about 81 508 HHD sessions during an 8-year period (January 2004-December 2011).
      Twenty-four patients switched to an alternative modality during the period.
      Combined technique survival (HHDc) as a composite of training (HHDtr) and at home
      (HHDhome) was analysed and clinical predictors of HHD modality failure since the
      commencement of the programme were calculated using Cox regression analysis.
      Technology-related interruptions to dialysis over a 12-month period and patient
      reported reasons for quitting the programme were analysed. RESULTS: Technique
      survival at 1, 2 and 5 years was 90.2, 87.4, 81.5% (HHDc) and 98.4, 95.4 and
      88.9% (HHDhome) when censored for training phase exits, death and
      transplantation. The combined HHDc modality switch rate is 1 in 192 patient
      months of dialysis follow-up. Age >60 years, diabetes, cardiac failure, unit
      decrease in Hb and increasing score of age-adjusted Charlson--comorbidity index
      were significantly associated with technique failure. Significant clinical
      predictors of HHD technique failure in a multivariate model were diabetes (P =
      0.002) and cardiac failure (P = 0.05). The majority (61%) switched to an
      alternative modality for non-medical reasons. The composite of operator error and
      mechanical breakdown resulting in temporary HHD technique failure was 0.7% per
      year. CONCLUSIONS: HHD training and technique failure rate are low. Technical
      errors are infrequent too. Diabetes and cardiac failure are associated with
      significant risk of technique failure. Although absolute rates are low, training
      failure is proportionally quite significant, highlighting the importance of
      reporting the composite technique failure rate (to include early HHD training
      phase) in HHD programmes.

PMID- 24078645
TI  - A multicentric, international matched pair analysis of body composition in
      peritoneal dialysis versus haemodialysis patients.
AB  - BACKGROUND: Volume status, lean and fat tissue are gaining interest as prognostic
      predictors in patients on dialysis. Comparative data in peritoneal dialysis (PD)
      versus haemodialysis (HD) patients are lacking. METHODS: In a cohort of PD
      (EuroBCM) and HD (Euclid database) patients, matched for country, gender, age and
      dialysis vintage, body composition was assessed by bioimpedance spectroscopy
      (BCM, Fresenius Medical Care). Time-averaged volume overload (TAVO) was defined
      as the mean of pre- and post-dialysis volume overload (VO), and relative (%)
      (TA)VO as (TA)VO/ECV. RESULTS: Four hundred and ninety-one matched pairs (55.2%
      males, median age 60.0 years) were included. The body mass index (BMI, PD = 26.5
      +/- 4.7 versus HD = 25.9 +/- 4.6 kg/m(2), P = 0.18 in males and 27.4 +/- 5.8
      versus 27.5 +/- 6.6 kg/m(2), P = 0.75 in females) and fat tissue index (males:
      11.5 +/- 5.3 versus 11.4 +/- 5.4 kg/m(2), P = 0.90, females: 14.8 +/- 6.7 versus
      15.4 +/- 7.2 kg/m(2), P = 0.30) were not different in PD versus HD patients,
      whereas the lean tissue index (LTI) was higher in PD versus HD patients (males:
      14.5 +/- 3.4 versus 13.7 +/- 3.1 kg/m(2), P = 0.001, females: 12.6 +/- 3.3 versus
      11.5 +/- 2.6 kg/m(2), P < 0.0001). VO/extracellular water (ECW) was not different
      between PD versus just before the HD treatment (males: 10.8 +/- 12.1 versus 9.2
      +/- 10.2%, P = 0.09; females: 6.5 +/- 10.8 versus 7.7 +/- 9.4%, P = 0.19). The
      relative TAVO was higher in PD versus HD (10.8 +/- 12.1% versus 3.2 +/- 11.2%,
      and 6.5 +/- 10.8% versus 1.2 +/- 10.9%, both P < 0.0001). CONCLUSIONS: The LTI
      was impaired, and this was more in males versus females, but was better preserved
      on PD versus HD, whereas fat tissue index (FTI) was increased, but not different
      between PD and HD. Volume overload was more present in PD versus HD when TAVO,
      but not when predialysis volume status, was used as a reference.

PMID- 24078647
TI  - Endovascular treatment of fusiform intracranial vertebral artery aneurysms using
      reconstructive techniques.
AB  - OBJECTIVE: To report our single center experience in the treatment of fusiform
      aneurysms involving the intracranial vertebral arteries using reconstructive
      endovascular techniques. PATIENTS AND METHODS: The neurointerventional database
      of our institution was retrospectively reviewed from June 2010 to February 2013.
      Patients who underwent endovascular treatment of fusiform intracranial vertebral
      artery aneurysms using reconstructive techniques were included in the analysis.
      Clinical presentation, size, reconstructive technique used, procedural
      complication, and clinical and angiographic follow-ups were included in the
      analysis. RESULTS: Nine patients, aged 41-76 years (mean 54.8 years), were
      included. Mean angiographic diameter of unruptured aneurysms was 8.4 mm (range 4
      14) while ruptured aneurysms averaged 6 mm (range 5-7 ). Two patients (two women)
      presented with acute subarachnoid hemorrhage (SAH). One patient with a large
      partially thrombosed aneurysm was treated with stent reconstruction requiring
      deployment of two stents (no coiling). There was one asymptomatic procedural
      complication (non-flow limiting cervical vertebral dissection). All patients had
      good clinical outcomes (modified Rankin Scale score of 0 or <=1) including the
      two patients that presented with SAH (Hunt and Hess grades 2 and 3). There were
      no late hemorrhages at a mean clinical follow-up of 12 months (6-24 months).
      Eight patients had angiographic follow-up (6-18 months, mean 10.5 months) and six
      demonstrated aneurysm occlusion with complete vessel reconstruction at the
      angiographic follow-up. CONCLUSIONS: The use of reconstructive techniques in the
      endovascular treatment of unruptured fusiform intracranial vertebral artery
      aneurysms is feasible, safe, and effective in the mid term. In patients
      presenting with SAH, however, the safety and effectiveness of these techniques
      remain unclear.

PMID- 24078648
TI  - Prevalence of the seven cardiovascular health metrics in a Mediterranean country:
      results from a cross-sectional study.
AB  - AIM: Primordial prevention is essential for reaching cardiovascular (CV) health.
      This is defined by seven health metrics identified by the American Heart
      Association. Aim of the present study was to assess prevalence and distribution
      of these seven CV health metrics within an unselected population. METHODS: All
      the 1110 consecutive individuals (mean age 56 +/- 13 years; 56% women) who agreed
      to be screened within the context of a national campaign of CV prevention were
      included. The following findings have been considered as ideal: never/former
      smoker, regular participation in physical activity, body mass index lower than
      25.0, healthy diet, cholesterol lower than 200 mg/dl, diabetes absence and a
      blood pressure lower than 120/80 mmHg. RESULTS: Participants presented, on
      average, 4.1 +/- 1.2 ideal CV health metrics, with a decreasing number across age
      groups. Only 10.4% covered more than five ideal CV health metrics and 8.3%
      covered less than three ideal health metrics. Only 1.9% of the study population
      met all the seven ideal metrics. In particular, only 34% (379 subjects) in our
      population presented an ideal level of cholesterol. The higher prevalence was
      observed in younger subjects (45%) and the lower (28%) in people older than 62
      years (P < 0.001). CONCLUSION: Prevalence of the seven CV health metrics was low
      in our population and just 1 in 10 met more than five ideal CV health metrics.
      Social initiatives and awareness policies from governments are mandatory to
      promote CV health. Further studies should address the impact of such CV metrics
      on several outcomes in European countries.

PMID- 24078649
TI  - Time trends of cigarette and waterpipe smoking among a cohort of school children
      in Irbid, Jordan, 2008-11.
AB  - BACKGROUND: Coordinated high-impact interventions and community-level changes in
      smoking behaviour norms effectively reduced prevalence of smoking among youth in
      many developed countries. Smoking trends among Jordanian adolescents are likely
      different than their Western counterparts and must be understood in the context
      of their daily lives to tailor interventions specifically for adolescents in this
      setting. METHODS: Between 2008 and 2011, a school-based longitudinal study was
      conducted in Irbid, Jordan. All seventh-grade students in 19 randomly selected
      schools (of 60) were surveyed annually for 4 years. Outcomes of interest were
      time trends in smoking behaviour, age at initiation and change in frequency of
      smoking. RESULTS: Among 1781 participants, baseline prevalence of current smoking
      (cigarettes or waterpipe) for boys was 22.9% and 8.7% for girls. Prevalence of
      ever-smoking and current any smoking, cigarette smoking, waterpipe smoking and
      dual cigarette/waterpipe smoking was significantly higher in boys than girls each
      year (P < 0.001). Smoking prevalence increased every year after year 2 for
      current smoking (P < 0.05) across all methods (any, cigarette, waterpipe and
      dual). At all time points for both boys and girls, prevalence of waterpipe
      smoking was higher than that of cigarette smoking (P < 0.001). CONCLUSION: This
      study shows intensive smoking patterns at early ages among Jordanian youth in
      Irbid, characterized by a predominance of waterpipe smoking and steeper age
      related increase in cigarette smoking. It also points to the possibility of
      waterpipe being the favourite method for introducing youth to tobacco, as well as
      being a vehicle for tobacco dependence and cigarette smoking.

PMID- 24078650
TI  - President's column.

PMID- 24078656
TI  - Testicular seminoma and non-seminoma: ESMO Clinical Practice Guidelines for
      diagnosis, treatment and follow-up.

PMID- 24078657
TI  - Gastric marginal zone lymphoma of MALT type: ESMO Clinical Practice Guidelines
      for diagnosis, treatment and follow-up.

PMID- 24078658
TI  - Waldenstrom's macroglobulinaemia: ESMO Clinical Practice Guidelines for
      diagnosis, treatment and follow-up.

PMID- 24078660
TI  - Newly diagnosed and relapsed epithelial ovarian carcinoma: ESMO Clinical Practice
      Guidelines for diagnosis, treatment and follow-up.

PMID- 24078661
TI  - Endometrial cancer: ESMO Clinical Practice Guidelines for diagnosis, treatment
      and follow-up.

PMID- 24078662
TI  - Oesophageal cancer: ESMO Clinical Practice Guidelines for diagnosis, treatment
      and follow-up.

PMID- 24078663
TI  - Gastric cancer: ESMO-ESSO-ESTRO Clinical Practice Guidelines for diagnosis,
      treatment and follow-up.

PMID- 24078664
TI  - Early colon cancer: ESMO Clinical Practice Guidelines for diagnosis, treatment
      and follow-up.

PMID- 24078665
TI  - Rectal cancer: ESMO Clinical Practice Guidelines for diagnosis, treatment and
      follow-up.

PMID- 24078666
TI  - Phytochrome-induced SIG2 expression contributes to photoregulation of phytochrome
      signalling and photomorphogenesis in Arabidopsis thaliana.
AB  - Chloroplast-localized sigma factor (SIG) proteins promote specificity of the
      plastid-encoded RNA polymerase. SIG2 function appears to be necessary for light
      grown Arabidopsis thaliana plants. Specific photoreceptors or light-dependent
      factors that impact the light-induced accumulation of SIG2 have not been
      reported. A molecular link between phytochromes and nuclear-encoded SIG2, which
      impacts photomorphogenesis specifically under red (R) and far-red (FR) light, is
      described here. Both phyA and phyB promote SIG2 transcript accumulation.
      Disruption of SIG2 results in R- and FR-specific defects in the inhibition of
      hypocotyl elongation and cotyledon expansion, although no impairments in these
      responses are detected for sig2 mutants under blue (B) or white (W) light. SIG2
      also impacts root elongation under W and R, and the R-dependent expression of
      PIF4, encoding a phytochrome-interacting factor, and HY2, which encodes a
      phytochrome chromophore biosynthetic enzyme. Whereas SIG2 apparently impacts the
      accumulation of the phytochromobilin (PPhiB) phytochrome chromophore, sig2
      mutants differ significantly from PPhiB mutants, primarily due to wavelength
      specific defects in photomorphogenesis and disruption of a distinct subset of
      phytochrome-dependent responses. The molecular link between phytochromes and SIG2
      is likely to be an important part of the co-ordination of gene expression to
      maintain stoichiometry between the nuclear-encoded phytochrome apoprotein and
      plastid-derived PPhiB, which combine to form photoactive phytochromes, and/or
      light-dependent SIG2 accumulation is involved in an inductive light signalling
      pathway co-ordinating components between nucleus and plastids. 

PMID- 24078667
TI  - Light-harvesting chlorophyll a/b-binding proteins, positively involved in
      abscisic acid signalling, require a transcription repressor, WRKY40, to balance
      their function.
AB  - The light-harvesting chlorophyll a/b-binding (LHCB) proteins are the apoproteins
      of the light-harvesting complex of photosystem II. In the present study, we
      observed that downregulation of any of the six LHCB genes resulted in abscisic
      acid (ABA)-insensitive phenotypes in seed germination and post-germination
      growth, demonstrating that LHCB proteins are positively involved in these
      developmental processes in response to ABA. ABA was required for full expression
      of different LHCB members and physiologically high levels of ABA enhanced LHCB
      expression. The LHCB members were shown to be targets of an ABA-responsive WRKY
      domain transcription factor, WRKY40, which represses LHCB expression to balance
      the positive function of the LHCBs in ABA signalling. These findings revealed
      that ABA is an inducer that fine-tunes LHCB expression at least partly through
      repressing the WRKY40 transcription repressor in stressful conditions in co
      operation with light, which allows plants to adapt to environmental challenges. 

PMID- 24078668
TI  - The Brassica rapa FLC homologue FLC2 is a key regulator of flowering time,
      identified through transcriptional co-expression networks.
AB  - The role of many genes and interactions among genes involved in flowering time
      have been studied extensively in Arabidopsis, and the purpose of this study was
      to investigate how effectively results obtained with the model species
      Arabidopsis can be applied to the Brassicacea with often larger and more complex
      genomes. Brassica rapa represents a very close relative, with its triplicated
      genome, with subgenomes having evolved by genome fractionation. The question of
      whether this genome fractionation is a random process, or whether specific genes
      are preferentially retained, such as flowering time (Ft) genes that play a role
      in the extreme morphological variation within the B. rapa species (displayed by
      the diverse morphotypes), is addressed. Data are presented showing that indeed Ft
      genes are preferentially retained, so the next intriguing question is whether
      these different orthologues of Arabidopsis Ft genes play similar roles compared
      with Arabidopsis, and what is the role of these different orthologues in B. rapa.
      Using a genetical-genomics approach, co-location of flowering quantitative trait
      loci (QTLs) and expression QTLs (eQTLs) resulted in identification of candidate
      genes for flowering QTLs and visualization of co-expression networks of Ft genes
      and flowering time. A major flowering QTL on A02 at the BrFLC2 locus co-localized
      with cis eQTLs for BrFLC2, BrSSR1, and BrTCP11, and trans eQTLs for the
      photoperiod gene BrCO and two paralogues of the floral integrator genes BrSOC1
      and BrFT. It is concluded that the BrFLC2 Ft gene is a major regulator of
      flowering time in the studied doubled haploid population. 

PMID- 24078669
TI  - Purinergic signalling: from discovery to current developments.
AB  - This lecture is about the history of the purinergic signalling concept. It begins
      with reference to the paper by Paton & Vane published in 1963, which identified
      non-cholinergic relaxation in response to vagal nerve stimulation in several
      species, although they suggested that it might be due to sympathetic adrenergic
      nerves in the vagal nerve trunk. Using the sucrose gap technique for simultaneous
      mechanical and electrical recordings in smooth muscle (developed while in
      Feldberg's department in the National Institute for Medical Research) of the
      guinea-pig taenia coli preparation (learned when working in Edith Bulbring's
      smooth muscle laboratory in Oxford Pharmacology), we showed that the
      hyperpolarizations recorded in the presence of antagonists to the classical
      autonomic neurotransmitters, acetylcholine and noradrenaline, were inhibitory
      junction potentials in response to non-adrenergic, non-cholinergic
      neurotransmission, mediated by intrinsic enteric nerves controlled by vagal and
      sacral parasympathetic nerves. We then showed that ATP satisfied the criteria
      needed to identify a neurotransmitter released by these nerves. Subsequently, it
      was shown that ATP is a cotransmitter in all nerves in the peripheral and central
      nervous systems. The receptors for purines and pyrimidines were cloned and
      characterized in the early 1990 s, and immunostaining showed that most non
      neuronal cells as well as nerve cells expressed these receptors. The physiology
      and pathophysiology of purinergic signalling is discussed.

PMID- 24078670
TI  - Postexercise syncope: Wingate syncope test and effective countermeasure.
AB  - Altered systemic haemodynamics following exercise can compromise cerebral
      perfusion and result in syncope. As the Wingate anaerobic test often induces
      presyncope, we hypothesized that a modified Wingate test could form the basis of
      a novel model for the study of postexercise syncope and a test bed for potential
      countermeasures. Along these lines, breathing through an impedance threshold
      device has been shown to increase tolerance to hypovolaemia, and could prove
      beneficial in the setting of postexercise syncope. Therefore, we hypothesized
      that a modified Wingate test followed by head-up tilt would produce postexercise
      syncope, and that breathing through an impedance threshold device
      (countermeasure) would prevent postexercise syncope in healthy individuals.
      Nineteen recreationally active men and women underwent a 60 deg head-up tilt
      during recovery from the Wingate test while arterial pressure, heart rate, end
      tidal CO2 and cerebral tissue oxygenation were measured on a control day and a
      countermeasure day. The duration of tolerable tilt was increased by a median time
      of 3 min 48 s with countermeasure in comparison to the control (P < 0.05), and
      completion of the tilt test increased from 42 to 67% with the countermeasure.
      During the tilt, mean arterial pressure was greater (108.0 +/- 4.1 versus 100.4
      +/- 2.4 mmHg; P < 0.05) with the countermeasure in comparison to the control.
      These data suggest that the Wingate syncope test produces a high incidence of
      presyncope, which is sensitive to countermeasures such as inspiratory impedance.

PMID- 24078671
TI  - Abscisic acid represses the transcription of chloroplast genes.
AB  - Numerous studies have shown effects of abscisic acid (ABA) on nuclear genes
      encoding chloroplast-localized proteins. ABA effects on the transcription of
      chloroplast genes, however, have not been investigated yet thoroughly. This work,
      therefore, studied the effects of ABA (75 MUM) on transcription and steady-state
      levels of transcripts in chloroplasts of basal and apical segments of primary
      leaves of barley (Hordeum vulgare L.). Basal segments consist of young cells with
      developing chloroplasts, while apical segments contain the oldest cells with
      mature chloroplasts. Exogenous ABA reduced the chlorophyll content and caused
      changes of the endogenous concentrations not only of ABA but also of cytokinins
      to different extents in the basal and apical segments. It repressed transcription
      by the chloroplast phage-type and bacteria-type RNA polymerases and lowered
      transcript levels of most investigated chloroplast genes drastically. ABA did not
      repress the transcription of psbD and a few other genes and even increased psbD
      mRNA levels under certain conditions. The ABA effects on chloroplast
      transcription were more pronounced in basal vs. apical leaf segments and enhanced
      by light. Simultaneous application of cytokinin (22 MUM 6-benzyladenine)
      minimized the ABA effects on chloroplast gene expression. These data demonstrate
      that ABA affects the expression of chloroplast genes differentially and points to
      a role of ABA in the regulation and coordination of the activities of nuclear and
      chloroplast genes coding for proteins with functions in photosynthesis. 

PMID- 24078672
TI  - Analysis of gene expression during the transition to climacteric phase in
      carnation flowers (Dianthus caryophyllus L.).
AB  - It has been generally thought that in ethylene-sensitive plants such as
      carnations, senescence proceeds irreversibly once the tissues have entered the
      climacteric phase. While pre-climacteric petal tissues have a lower sensitivity
      to ethylene, these tissues are converted to the climacteric phase at a critical
      point during flower development. In this study, it is demonstrated that the
      senescence process initiated by exogenous ethylene is reversible in carnation
      petals. Petals treated with ethylene for 12h showed sustained inrolling and
      senescence, while petals treated with ethylene for 10h showed inrolling followed
      by recovery from inrolling. Reverse transcription-PCR analysis revealed
      differential expression of genes involved in ethylene biosynthesis and ethylene
      signalling between 10h and 12h ethylene treatment. Ethylene treatment at or
      beyond 12h (threshold time) decreased the mRNA levels of the receptor genes
      (DcETR1, DcERS1, and DcERS2) and DcCTR genes, and increased the ethylene
      biosynthesis genes DcACS1 and DcACO1. In contrast, ethylene treatment under the
      threshold time caused a transient decrease in the receptor genes and DcCTR genes,
      and a transient increase in DcACS1 and DcACO1. Sustained DcACS1 accumulation is
      correlated with decreases in DcCTR genes and increase in DcEIL3 and indicates
      that tissues have entered the climacteric phase and that senescence proceeds
      irreversibly. Inhibition of ACS (1-aminocyclopropane-1-carboxylic acid synthase)
      prior to 12h ethylene exposure was not able to prevent reduction in transcripts
      of DcCTR genes, yet suppressed transcript of DcACS1 and DcACO1. This leads to the
      recovery from inrolling of the petals, indicating that DcACS1 may act as a
      signalling molecule in senescence of flowers. 

PMID- 24078673
TI  - Ontogeny strongly and differentially alters leaf economic and other key traits in
      three diverse Helianthus species.
AB  - The leaf economics spectrum (LES) describes large cross-species variation in
      suites of leaf functional traits ranging from resource-acquisitive to resource
      conservative strategies. Such strategies have been integral in explaining plant
      adaptation to diverse environments, and have been linked to numerous ecosystem
      processes. The LES has previously been found to be significantly modulated by
      climate, soil fertility, biogeography, growth form, and life history. One largely
      unexplored aspect of LES variation, whole-plant ontogeny, is investigated here
      using multiple populations of three very different species of sunflower:
      Helianthus annuus, Helianthus mollis, and Helianthus radula. Plants were grown
      under environmentally controlled conditions and assessed for LES and related
      traits at four key developmental stages, using recently matured leaves to
      standardize for leaf age. Nearly every trait exhibited a significant ontogenetic
      shift in one or more species, with trait patterns differing among populations and
      species. Photosynthetic rate, leaf nitrogen concentration, and leaf mass per area
      exhibited surprisingly large changes, spanning over two-thirds of the original
      cross-species LES variation and shifting from resource-acquisitive to resource
      conservative strategies as the plants matured. Other traits being investigated in
      relation to the LES, such as leaf water content, pH, and vein density, also
      showed large changes. The finding that ontogenetic variation in LES strategy can
      be substantial leads to a recommendation of standardization by developmental
      stage when assessing 'species values' of labile traits for comparative
      approaches. Additionally, the substantial ontogenetic trait shifts seen within
      single individuals provide an opportunity to uncover the contribution of gene
      regulatory changes to variation in LES traits. 

PMID- 24078674
TI  - Biologic discontinuation studies: a systematic review of methods; comment on the
      article by Yoshida et al.

PMID- 24078675
TI  - Loss of phosphatase and tensin homolog (PTEN) in myeloid cells controls
      inflammatory bone destruction by regulating the osteoclastogenic potential of
      myeloid cells.
AB  - OBJECTIVE: Local bone destruction in rheumatic diseases, which often leads to
      disability and severely reduced quality of life, is almost exclusively mediated
      by osteoclasts. Therefore, it is important to understand pathways regulating the
      generation of osteoclasts. Here, we analysed the impact of the Phosphoinositide-3
      Kinase (PI3K)/Phosphatase and tensin homolog (PTEN) axis on osteoclast generation
      and bone biology under basal and inflammatory conditions. METHODS: We analysed
      osteoclastogenesis of wildtype (wt) and PTEN(-/-) cells in vitro and in vivo, pit
      resorption and qPCR of osteoclasts in vitro. Mice with a myeloid cell-specific
      deletion of PTEN and wt littermate mice were investigated by bone
      histomorphometry and clinical and histological assessment in the human tumour
      necrosis factor (TNF)-transgenic (hTNFtg) arthritis model. RESULTS: We show that
      myeloid-specific PTEN(-/-) mice display increased osteoclastogenesis in vitro and
      in vivo compared to wt mice. Loss of PTEN did not affect the generation or
      survival of osteoclast precursor cells. However, PTEN deficiency greatly enhanced
      receptor activator of nuclear factor kappa-B ligand (RANKL)-induced expression of
      the master transcription factor of osteoclastogenesis, nuclear factor of
      activated T-cells, cytoplasmic 1 (NFATc1), resulting in markedly increased
      terminal differentiation of osteoclasts in vitro. We also observed increased
      osteoclastogenesis under inflammatory conditions in the hTNFtg mouse model of
      arthritis, where hTNFtg/myeloid-specific PTEN(-/-) mice displayed enhanced local
      bone destruction as well as osteoclast formation in the inflamed joints. The
      extent of synovial inflammation, however, as well as recruitment of osteoclast
      precursor cells was not different between wt and myeloid-specific PTEN(-/-) mice.
      CONCLUSIONS: These data demonstrate that loss of PTEN and, therefore, sustained
      PI3-Kinase signalling in myeloid cells especially, elevates the osteoclastogenic
      potential of myeloid cells, leading to enhanced inflammatory local bone
      destruction. Therefore, although our study allows no direct translational
      conclusion since we used a conditional knockout approach, the therapeutic
      targeting of the PI3-Kinase pathway may be of benefit in preventing structural
      joint damage.

PMID- 24078676
TI  - Response to 'Are steroids required for induction therapy and relapses in lupus
      nephritis?' by Abud-Mendoza et al.

PMID- 24078677
TI  - Cross-sectional and longitudinal associations between circulating leptin and knee
      cartilage thickness in older adults.
AB  - OBJECTIVE: To investigate cross-sectional and longitudinal associations between
      serum leptin levels and knee cartilage thickness in older adults. METHODS: A
      prospective cohort of 163 randomly selected subjects (mean 63 years, range 52-78,
      46% women) was studied. Knee cartilage thickness at medial tibial, lateral
      tibial, femoral and patellar sites was determined using T1-weighted fat
      suppressed MRI. Serum leptin levels were measured by radioimmunoassay.
      Radiographic osteoarthritis, body fat (%), trunk fat (%), weight and height were
      measured, and body mass index (BMI) was calculated. RESULTS: Cross-sectionally,
      serum levels of leptin were negatively associated with femoral (beta: -0.013, 95%
      CI -0.022 to -0.003), medial tibial (beta: -0.009, 95% CI -0.018 to -0.001),
      lateral tibial (beta: -0.012, 95% CI -0.021 to -0.003) and patellar (beta: 
      0.014, 95% CI -0.026 to -0.002) cartilage thickness after adjustment for
      covariates. Moreover, BMI, trunk fat and total body fat were negatively
      associated with cartilage thickness, and the significant associations disappeared
      after further adjustment for leptin. Longitudinally, both baseline leptin and
      change in leptin were associated with greater changes in medial tibial cartilage
      thickness (beta: -0.004, 95% CI -0.007 to -0.001 and beta: -0.009, 95% CI -0.018
      to -0.001, respectively) in multivariable analyses. CONCLUSIONS: Serum levels of
      leptin are independently and consistently associated with reduced cartilage
      thickness cross-sectionally and longitudinally. In addition, the associations
      between adiposity measures and cartilage thickness are mediated by leptin,
      suggesting leptin may play a key role in cartilage thinning.

PMID- 24078678
TI  - Genetic architecture of floral traits in Iris hexagona and Iris fulva.
AB  - The formation of hybrids among closely related species has been observed in
      numerous plant taxa. Selection by pollinators on floral traits can act as an
      early reproductive isolating barrier and may be especially important when there
      is overlap in distribution and flowering time. In this study, we use Quantitative
      Trait Locus (QTL) mapping based on 293 codominant SNP markers in an F2 population
      (n = 328) to assess the size, magnitude, and location of the genetic regions
      controlling floral traits known to be important for pollinator attraction in 2
      species of Lousiana Irises, Iris fulva and Iris hexagona. We also evaluate
      correlations among F2 traits and identify transgression in the hybrid population.
      Overall, we observe that differences in most floral traits between I. fulva and
      I. hexagona are controlled by multiple QTLs and are distributed across several
      linkage groups. We also find evidence of transgression at several QTL, suggesting
      that hybridization can contribute to generating phenotypic variation, which may
      be adaptive in rapidly changing environments. 

PMID- 24078679
TI  - MHC class II beta genes in the endangered Hainan Eld's deer (Cervus eldi
      hainanus).
AB  - Contrary to neutral markers, the major histocompatibility complex (MHC) can
      reflect the fitness and adaptive potential of a given species due to its
      association with the immune system. For this reason, the use of MHC in endangered
      wildlife management has increased greatly in recent years. Here, we isolated
      complementary DNA (cDNA) and genomic DNA (gDNA) sequences to characterize the MHC
      class II beta genes in Hainan Eld's deer (Cervus eldi hainanus), a highly
      endangered cervid, which recovered from a severe population bottleneck consisting
      of 26 animals. Analysis of 7 individuals revealed the presence of 3 DRB and 3 DQB
      putatively functional gDNA sequences. The Ceel-DRB and DQB sequences displayed
      high variability in exon 2, and most nonsynonymous substitutions were detected in
      this region. Phylogenetic analysis indicated that trans-species evolution of MHC
      class II beta might occur in the Cervinae subfamily. Comparison of the number of
      sequences between gDNA and cDNA revealed that all sequences isolated from the
      genome were detectable in the cDNA libraries derived from different tissues
      (including the liver, kidney, and spleen), suggesting none of these sequences
      were derived from silent genes or pseudogenes. Characterization of the MHC class
      II beta genes may lay the foundation for future studies on genetic structure,
      mate choice, and viability analysis in Hainan Eld's deer. 

PMID- 24078680
TI  - The role of heritable and dietary factors in the sexual signal of a Hispaniolan
      Anolis lizard, Anolis distichus.
AB  - The diversity of sexual signals is astounding, and divergence in these traits is
      believed to be associated with the early stages of speciation. An increasing
      number of studies also suggest a role for natural selection in driving signal
      divergence for effective transmission in heterogeneous environments. Both
      speciation and adaptive divergence, however, are contingent on the sexual signal
      being heritable, yet this often remains assumed and untested. It is particularly
      critical that the heritability of carotenoid-based sexual signals is investigated
      because such traits may instead be phenotypically plastic indicators of an
      individual's quality that exhibit no or little heritable variation. We present
      the first study to investigate the relative contribution of genetic and
      environmental factors to the striking diversity of dewlap color and pattern in
      Anolis lizards. Using a breeding experiment with Anolis distichus populations
      exhibiting different dewlap phenotypes, we raise F1 offspring in a common garden
      experiment to assess whether dewlap color is inherited. We follow this with
      carotenoid supplementation to investigate the influence of dietary pigments to
      dewlap color variation. We find significant differences in several aspects of
      dewlap color and pattern to persist to the F1 generation (fathers: N = 19; F1
      males: N = 50; P < 0.01) with no change in dewlap phenotype with carotenoid
      supplementation (N = 52; P > 0.05). These results strongly support that genetic
      differences underlie dewlap color variation, thereby satisfying a key requirement
      of natural selection. Our findings provide an important stepping-stone to
      understanding the evolution of an incredibly diverse signal important for sexual
      selection and species recognition. 

PMID- 24078681
TI  - At risk of population decline? An ecological and genetic approach to the
      threatened palm species Butia eriospatha (Arecaceae) of Southern Brazil.
AB  - To estimate the risk of population decline for the threatened palm species Butia
      eriospatha, we investigated the patterns of demography, natural regeneration,
      herbivory, and the levels of genetic diversity using 9 microsatellite loci from
      both adults and seedlings sampled from 4 populations in Southern Brazil (n =
      330). Our results indicate that cattle grazing in B. eriospatha population areas
      severely affect their demographic structure. Three B. eriospatha populations
      showed a bimodal age structure made up of adult plants and seedlings and high
      rates (>77%) of livestock herbivory. For 1 population, we describe and quantify
      for the first time the occurrence of 6 ontogenetic stages for this threatened
      palm species. Populations of B. eriospatha showed high levels of genetic
      differentiation (F ST adult plants = 0.287, F ST seedlings = 0.175). The amount
      of observed heterozygosity differed significantly between small (H O = 0.329) and
      large populations (H O = 0.461), indicating that small populations can be more
      susceptible to genetic drift. With no recruitment and a mortality rate of 2.0%,
      we show that the populations investigated in this study would be at an extremely
      high risk of local extinction, with a greater than 50% reduction in the effective
      population size, in the next 40 years. Although this study highlights the
      importance of analyzing both population ecology parameters and genetic data to
      better understand the level of risk facing threatened species, we emphasize that
      policy actions are urgently needed for effective conservation of this vulnerable
      biological resource. 

PMID- 24078682
TI  - Molecular causes of transcriptional response: a Bayesian prior knowledge
      approach.
AB  - MOTIVATION: The abundance of many transcripts changes significantly in response
      to a variety of molecular and environmental perturbations. A key question in this
      setting is as follows: what intermediate molecular perturbations gave rise to the
      observed transcriptional changes? Regulatory programs are not exclusively
      governed by transcriptional changes but also by protein abundance and post
      translational modifications making direct causal inference from data difficult.
      However, biomedical research over the last decades has uncovered a plethora of
      causal signaling cascades that can be used to identify good candidates explaining
      a specific set of transcriptional changes. METHODS: We take a Bayesian approach
      to integrate gene expression profiling with a causal graph of molecular
      interactions constructed from prior biological knowledge. In addition, we define
      the biological context of a specific interaction by the corresponding Medical
      Subject Headings terms. The Bayesian network can be queried to suggest upstream
      regulators that can be causally linked to the altered expression profile.
      RESULTS: Our approach will treat candidate regulators in the right biological
      context preferentially, enables hierarchical exploration of resulting hypotheses
      and takes the complete network of causal relationships into account to arrive at
      the best set of upstream regulators. We demonstrate the power of our method on
      distinct biological datasets, namely response to dexamethasone treatment, stem
      cell differentiation and a neuropathic pain model. In all cases relevant
      biological insights could be validated. AVAILABILITY AND IMPLEMENTATION: Source
      code for the method is available upon request.

PMID- 24078683
TI  - DockAFM: benchmarking protein structures by docking under AFM topographs.
AB  - Proteins can adopt a variety of conformations. We present a simple server for
      scoring the agreement between 3D atomic structures and experimental envelopes
      obtained by atomic force microscopy. Three different structures of
      immunoglobulins (IgG) or blood coagulation factor V activated were tested and
      their agreement with several topographical surfaces was computed. This approach
      can be used to test structural variability within a family of proteins.
      AVAILABILITY AND IMPLEMENTATION: DockAFM is available at
      http://biodev.cea.fr/dockafm.

PMID- 24078684
TI  - INVEX--a web-based tool for integrative visualization of expression data.
AB  - SUMMARY: Gene expression or metabolomics data generated from clinical settings
      are often associated with multiple metadata (i.e. diagnosis, genotype, gender,
      etc.). It is of great interest to analyze and to visualize the data in these
      contexts. Here, we introduce INVEX-a novel web-based tool that integrates the
      server-side capabilities for data analysis with the browse-based technology for
      data visualization. INVEX has two key features: (i) flexible differential
      expression analysis for a wide variety of experimental designs; and (ii)
      interactive visualization within the context of metadata and biological
      annotations. INVEX has built-in support for gene/metabolite annotation and a
      fully functional heatmap builder. AVAILABILITY AND IMPLEMENTATION: Freely
      available at http://www.invex.ca.

PMID- 24078685
TI  - Lep-MAP: fast and accurate linkage map construction for large SNP datasets.
AB  - MOTIVATION: Current high-throughput sequencing technologies allow cost-efficient
      genotyping of millions of single nucleotide polymorphisms (SNPs) for hundreds of
      samples. However, the tools that are currently available for constructing linkage
      maps are not well suited for large datasets. Linkage maps of large datasets would
      be helpful in de novo genome assembly by facilitating comprehensive genome
      validation and refinement by enabling chimeric scaffold detection, as well as in
      family-based linkage and association studies, quantitative trait locus mapping,
      analysis of genome synteny and other complex genomic data analyses. RESULTS: We
      describe a novel tool, called Lepidoptera-MAP (Lep-MAP), for constructing
      accurate linkage maps with ultradense genome-wide SNP data. Lep-MAP is fast and
      memory efficient and largely automated, requiring minimal user interaction. It
      uses simultaneously data on multiple outbred families and can increase linkage
      map accuracy by taking into account achiasmatic meiosis, a special feature of
      Lepidoptera and some other taxa with no recombination in one sex (no
      recombination in females in Lepidoptera). We demonstrate that Lep-MAP outperforms
      other methods on real and simulated data. We construct a genome-wide linkage map
      of the Glanville fritillary butterfly (Melitaea cinxia) with over 40 000 SNPs.
      The data were generated with a novel in-house SOLiD restriction site-associated
      DNA tag sequencing protocol, which is described in the online supplementary
      material. AVAILABILITY AND IMPLEMENTATION: Java source code under GNU general
      public license with the compiled classes and the datasets are available from
      http://sourceforge.net/users/lep-map.

PMID- 24078686
TI  - Fuzzy optimization for detecting enzyme targets of human uric acid metabolism.
AB  - MOTIVATION: Mathematical modeling and optimization have been used for detecting
      enzyme targets in human metabolic disorders. Such optimal drug design methods are
      generally differentiated as two stages, identification and decision-making, to
      find optimal targets. We developed a unified method named fuzzy equal metabolic
      adjustment to formulate an optimal enzyme target design problem for drug
      discovery. The optimization framework combines the identification of enzyme
      targets and a decision-making strategy simultaneously. The objectives of this
      algorithm include evaluations of the therapeutic effect of target enzymes, the
      adverse effects of drugs and the minimum effective dose (MED). RESULTS: An
      existing generalized mass action system model of human uric acid (UA) metabolism
      was used to formulate the fuzzy optimization method for detecting two types of
      enzymopathies: hyperuricemia caused by phosphoribosylpyrophosphate synthetase
      (PRPPS) overactivity and Lesch-Nyhan syndrome. The fuzzy objectives were set so
      that the concentrations of the metabolites were as close as possible to the
      healthy levels. The target design included a diet control of ribose-5-phospahate
      (R5P). The diet control of R5P served as an extra remedy to reduce phosphate
      uptake entering the purine metabolic pathway, so that we could obtain a more
      satisfactory treatment than obtained for those without a diet control. Moreover,
      enhancing UA excretion resulted in an effective treatment of hyperuricemia caused
      by PRPPS overactivity. This result correlates with using probenecid and
      benbromazone, which are uricosuric agents present in current clinical
      medications. By contrast, the Lesch-Nyhan syndrome required at least three enzyme
      targets to cure hyperuricemia.

PMID- 24078687
TI  - Syndecan-1, a cell surface proteoglycan, negatively regulates initial leukocyte
      recruitment to the brain across the choroid plexus in murine experimental
      autoimmune encephalomyelitis.
AB  - The cell surface heparan sulfate proteoglycan, syndecan-1, has been reported to
      be a negative regulator of various inflammatory processes, but its precise mode
      of action is poorly defined. In this study, we use the murine model of the 35-55
      peptide of myelin oligodendrocyte glycoprotein-induced experimental autoimmune
      encephalomyelitis (EAE), a T lymphocyte-mediated inflammation where the steps in
      disease development and recovery are well characterized, to decipher how syndecan
      1 impacts on the inflammatory reaction. Syndecan-1 knockout (Sdc-1(-/-)) mice
      show enhanced disease severity and impaired recovery. The use of bone marrow
      chimeric mice reveals that both an immune cell and a CNS-resident source of
      syndecan-1 contribute to this phenotype. Epithelial cells of the choroid plexus,
      where initial CCL20-induced leukocyte recruitment to the brain occurs, are
      identified as the predominant site of syndecan-1 expression. Syndecan-1 is lost
      from this site during the course of EAE by shedding into the cerebrospinal fluid,
      which correlates with loss of epithelial cell surface-bound CCL20 and is
      associated with the upregulation of IL-6 expression. In Sdc-1(-/-) mice, early
      leukocyte recruitment via the choroid plexus is enhanced, and IL-6 is elevated,
      which collectively results in higher numbers of the disease inducing Th17 cells
      in the CNS, thereby contributing to enhanced disease severity. Furthermore, Sdc
      1(-/-) mice have intrinsically elevated plasma cell numbers and higher myelin
      oligodendrocyte glycoprotein-specific Ab levels during EAE, which we propose
      contributes to impaired recovery. Our data identify the choroid plexus epithelium
      as a novel source of IL-6 in EAE and demonstrate that its expression negatively
      correlates with syndecan-1 expression at this site. 

PMID- 24078689
TI  - Large spectrum of HLA-C recognition by killer Ig-like receptor (KIR)2DL2 and
      KIR2DL3 and restricted C1 SPECIFICITY of KIR2DS2: dominant impact of
      KIR2DL2/KIR2DS2 on KIR2D NK cell repertoire formation.
AB  - The interactions of killer Ig-like receptor 2D (KIR2D) with HLA-C ligands
      contribute to functional NK cell education and regulate NK cell functions.
      Although simple alloreactive rules have been established for inhibitory KIR2DL,
      those governing activating KIR2DS function are still undefined, and those
      governing the formation of the KIR2D repertoire are still debated. In this study,
      we investigated the specificity of KIR2DL1/2/3 and KIR2DS1/2, dissected each
      KIR2D function, and assessed the impact of revisited specificities on the KIR2D
      NK cell repertoire formation from a large cohort of 159 KIR and HLA genotyped
      individuals. We report that KIR2DL2(+) and KIR2DL3(+) NK cells reacted similarly
      against HLA-C(+) target cells, irrespective of C1 or C2 allele expression. In
      contrast, KIR2DL1(+) NK cells specifically reacted against C2 alleles, suggesting
      a larger spectrum of HLA-C recognition by KIR2DL2 and KIR2DL3 than KIR2DL1.
      KIR2DS2(+) KIR2DL2(-) NK cell clones were C1-reactive irrespective of their HLA-C
      environment. However, when KIR2DS2 and KIR2DL2 were coexpressed, NK cell
      inhibition via KIR2DL2 overrode NK cell activation via KIR2DS2. In contrast,
      KIR2DL1 and KIR2DS2 had an additive enhancing effect on NK cell responses against
      C1C1 target cells. KIR2DL2/3/S2 NK cells predominated within the KIR repertoire
      in KIR2DL2/S2(+) individuals. In contrast, the KIR2DL1/S1 NK cell compartment is
      dominant in C2C2 KIR2DL2/S2(-) individuals. Moreover, our results suggest that
      together with KIR2DL2, activating KIR2DS1 and KIR2DS2 expression limits KIR2DL1
      acquisition on NK cells. Altogether, our results suggest that the NK cell
      repertoire is remolded by the activating and inhibitory KIR2D and their cognate
      ligands. 

PMID- 24078688
TI  - Identification of a tissue-specific, C/EBPbeta-dependent pathway of
      differentiation for murine peritoneal macrophages.
AB  - Macrophages and dendritic cells (DC) are distributed throughout the body and play
      important roles in pathogen detection and tissue homeostasis. In tissues,
      resident macrophages exhibit distinct phenotypes and activities, yet the
      transcriptional pathways that specify tissue-specific macrophages are largely
      unknown. We investigated the functions and origins of two peritoneal macrophage
      populations in mice: small and large peritoneal macrophages (SPM and LPM,
      respectively). SPM and LPM differ in their ability to phagocytose apoptotic
      cells, as well as in the production of cytokines in response to LPS. In steady
      state conditions, SPM are sustained by circulating precursors, whereas LPM are
      maintained independently of hematopoiesis; however, both populations are
      replenished by bone marrow precursors following radiation injury. Transcription
      factor analysis revealed that SPM and LPM express abundant CCAAT/enhancer binding
      protein (C/EBP)-beta. Cebpb(-/-) mice exhibit elevated numbers of SPM-like cells
      but lack functional LPM. Alveolar macrophages are also missing in Cebpb(-/-)
      mice, although macrophage populations in the spleen, kidney, skin, mesenteric
      lymph nodes, and liver are normal. Adoptive transfer of SPM into Cebpb(-/-) mice
      results in SPM differentiation into LPM, yet donor SPM do not generate LPM after
      transfer into C/EBPbeta-sufficient mice, suggesting that endogenous LPM inhibit
      differentiation by SPM. We conclude that C/EBPbeta plays an intrinsic, tissue
      restricted role in the generation of resident macrophages. 

PMID- 24078691
TI  - The MyD88 pathway in plasmacytoid and CD4+ dendritic cells primarily triggers
      type I IFN production against measles virus in a mouse infection model.
AB  - Infection by measles virus (MV) induces type I IFN via the retinoic acid
      inducible gene I/melanoma differentiation-associated gene 5/mitochondrial
      antiviral signaling protein (MAVS) pathway in human cells. However, the in vivo
      role of the MAVS pathway in host defense against MV infection remains
      undetermined. CD150 transgenic (Tg) mice, which express human CD150, an entry
      receptor for MV, with the disrupting IFNR gene (Ifnar(-/-)), are susceptible to
      MV and serve as a model for MV infection. In this study, we generated
      CD150Tg/Mavs(-/-) mice and examined MV permissiveness compared with that in
      CD150Tg/Ifnar(-/-) mice. MV replicated mostly in the spleen of i.p.-infected
      CD150Tg/Ifnar(-/-) mice. Strikingly, CD150Tg/Mavs(-/-) mice were not permissive
      to MV in vivo because of substantial type I IFN induction. MV barely replicated
      in any other organs tested. When T cells, B cells, and dendritic cells (DCs)
      isolated from CD150Tg/Mavs(-/-) splenocytes were cultured with MV in vitro, only
      the DCs produced type I IFN. In vitro infection analysis using CD150Tg/Mavs(-/-)
      DC subsets revealed that CD4(+) and plasmacytoid DCs, but not CD8alpha(+) and
      CD8alpha(-)CD4(-) double negative DCs, were exclusively involved in type I IFN
      production in response to MV infection. Because CD150Tg/Mavs(-/-) mice turned
      permissive to MV by anti-IFNAR Ab, type I IFN produced by CD4(+) DCs and
      plasmacytoid DCs plays a critical role in antiviral protection for neighboring
      cells expressing IFNAR. Induction of type I IFN in these DC subsets was abolished
      by the MyD88 inhibitory peptide. Thus, production of type I IFN occurs via the
      MyD88-dependent and MAVS-independent signaling pathway during MV infection. 

PMID- 24078690
TI  - Human CD4+CD3- innate-like T cells provide a source of TNF and lymphotoxin
      alphabeta and are elevated in rheumatoid arthritis.
AB  - Innate lymphoid cells encompass a diverse array of lymphocyte subsets with unique
      phenotype that initiate inflammation and provide host defenses in specific
      microenvironments. In this study, we identify a rare human CD4(+)CD3(-) innate
      like lymphoid population with high TNF expression that is enriched in blood from
      patients with rheumatoid arthritis. These CD4(+)CD3(-) cells belong to the T cell
      lineage, but the lack of AgR at the cell surface renders them nonresponsive to
      TCR-directed stimuli. By developing a culture system that sustains survival, we
      show that CD4(+)CD3(-) innate-like T cells display IL-7-dependent induction of
      surface lymphotoxin-alphabeta, demonstrating their potential to modify tissue
      microenvironments. Furthermore, expression of CCR6 on the CD4(+)CD3(-) population
      defines a CD127(high) subset that is highly responsive to IL-7. This CD4(+)CD3(-)
      population is enriched in the peripheral blood from rheumatoid arthritis
      patients, suggesting a link to their involvement in chronic inflammatory disease.

PMID- 24078692
TI  - Cooperation of TLR12 and TLR11 in the IRF8-dependent IL-12 response to Toxoplasma
      gondii profilin.
AB  - TLRs play a central role in the innate recognition of pathogens and the
      activation of dendritic cells (DCs). In this study, we establish that, in
      addition to TLR11, TLR12 recognizes the profilin protein of the protozoan
      parasite Toxoplasma gondii and regulates IL-12 production by DCs in response to
      the parasite. Similar to TLR11, TLR12 is an endolysosomal innate immune receptor
      that colocalizes and interacts with UNC93B1. Biochemical experiments revealed
      that TLR11 and TLR12 directly bind to T. gondii profilin and are capable of
      forming a heterodimer complex. We also establish that the transcription factor
      IFN regulatory factor 8, not NF-kappaB, plays a central role in the regulation of
      the TLR11- and TLR12-dependent IL-12 response of DCs. These results suggest a
      central role for IFN regulatory factor 8-expressing CD8(+) DCs in governing the
      TLR11- and TLR12-mediated host defense against T. gondii. 

PMID- 24078693
TI  - Proapoptotic chemotherapeutic drugs induce noncanonical processing and release of
      IL-1beta via caspase-8 in dendritic cells.
AB  - The identification of noncanonical (caspase-1-independent) pathways for IL-1beta
      production has unveiled an intricate interplay between inflammatory and death
      inducing signaling platforms. We found a heretofore unappreciated role for
      caspase-8 as a major pathway for IL-1beta processing and release in murine bone
      marrow-derived dendritic cells (BMDC) costimulated with TLR4 agonists and
      proapoptotic chemotherapeutic agents such as doxorubicin (Dox) or staurosporine
      (STS). The ability of Dox to stimulate release of mature (17-kDa) IL-1beta was
      nearly equivalent in wild-type (WT) BMDC, Casp1(-/-)Casp11(-/-) BMDC, WT BMDC
      treated with the caspase-1 inhibitor YVAD, and BMDC lacking the inflammasome
      regulators ASC, NLRP3, or NLRC4. Notably, Dox-induced production of mature IL
      1beta was temporally correlated with caspase-8 activation in WT cells and greatly
      suppressed in Casp8(-/-)Rip3(-/-) or Trif(-/-) BMDC, as well as in WT BMDC
      treated with the caspase-8 inhibitor, IETD. Similarly, STS stimulated robust IL
      1beta processing and release in Casp1(-/-)Casp11(-/-) BMDC that was IETD
      sensitive. These data suggest that TLR4 induces assembly of caspase-8-based
      signaling complexes that become licensed as IL-1beta-converting enzymes in
      response to Dox and STS. The responses were temporally correlated with
      downregulation of cellular inhibitor of apoptosis protein 1, suggesting
      suppressive roles for this and likely other inhibitor of apoptosis proteins on
      the stability and/or proteolytic activity of the caspase-8 platforms. Thus,
      proapoptotic chemotherapeutic agents stimulate the caspase-8-mediated processing
      and release of IL-1beta, implicating direct effects of such drugs on a
      noncanonical inflammatory cascade that may modulate immune responses in tumor
      microenvironments. 

PMID- 24078694
TI  - Characterization of distinct immunophenotypes across pediatric brain tumor types.
AB  - Despite increasing evidence that antitumor immune control exists in the pediatric
      brain, these findings have yet to be exploited successfully in the clinic. A
      barrier to development of immunotherapeutic strategies in pediatric brain tumors
      is that the immunophenotype of these tumors' microenvironment has not been
      defined. To address this, the current study used multicolor FACS of disaggregated
      tumor to systematically characterize the frequency and phenotype of infiltrating
      immune cells in the most common pediatric brain tumor types. The initial study
      cohort consisted of 7 pilocytic astrocytoma (PA), 19 ependymoma (EPN), 5
      glioblastoma (GBM), 6 medulloblastoma (MED), and 5 nontumor brain (NT) control
      samples obtained from epilepsy surgery. Immune cell types analyzed included both
      myeloid and T cell lineages and respective markers of activated or suppressed
      functional phenotypes. Immune parameters that distinguished each of the tumor
      types were identified. PA and EPN demonstrated significantly higher infiltrating
      myeloid and lymphoid cells compared with GBM, MED, or NT. Additionally, PA and
      EPN conveyed a comparatively activated/classically activated myeloid cell-skewed
      functional phenotype denoted in particular by HLA-DR and CD64 expression. In
      contrast, GBM and MED contained progressively fewer infiltrating leukocytes and
      more muted functional phenotypes similar to that of NT. These findings were
      recapitulated using whole tumor expression of corresponding immune marker genes
      in a large gene expression microarray cohort of pediatric brain tumors. The
      results of this cross-tumor comparative analysis demonstrate that different
      pediatric brain tumor types exhibit distinct immunophenotypes, implying that
      specific immunotherapeutic approaches may be most effective for each tumor type. 

PMID- 24078695
TI  - IL-1 induces proinflammatory leukocyte infiltration and regulates fibroblast
      phenotype in the infarcted myocardium.
AB  - In the infarcted myocardium, activation of the inflammatory cascade clears the
      wound from dead cells, whereas stimulating matrix degradation and chamber
      dilation, thus contributing to the development of heart failure. IL-1 is
      critically involved in the postinfarction inflammatory reaction and mediates
      adverse dilative remodeling. We hypothesized that IL-1 may regulate
      postinfarction repair and remodeling through cell-specific actions on leukocytes
      and fibroblasts. Flow cytometry demonstrated that in mouse infarcts, early
      recruitment of proinflammatory Ly6C(hi) cells expressing IL-1R1, the signaling
      receptor for IL-1, was followed by infiltration with cells expressing the decoy
      receptor, IL-1R2. Increased expression of IL-1R2 may serve to terminate IL-1
      driven inflammation after infarction. Loss of IL-1 signaling in IL-1R1 null mice
      globally attenuated leukocyte recruitment, reducing the number of infiltrating
      Ly6C(hi) and Ly6C(lo) cells. Nonmyeloid CD11b(-) cells harvested during the
      inflammatory phase of cardiac repair exhibited marked upregulation of chemokines
      and cytokines; their inflammatory activation was IL-1R1 dependent. Moreover, IL
      1beta attenuated TGF-beta-induced contractile activity of fibroblasts populating
      collagen pads, attenuated alpha-smooth muscle actin expression, and stimulated
      matrix metalloproteinase synthesis in an IL-1R1-dependent manner. The effects of
      IL-1 on TGF-beta responses in cardiac fibroblasts were not due to direct effects
      on Smad activation, but were associated with endoglin suppression and accentuated
      expression of bone morphogenetic protein and activin membrane-bound inhibitor, a
      negative regulator of TGF-beta signaling. IL-1 may orchestrate fibroblast
      responses in the infarct; early stimulation of fibroblast IL-1R1 signaling during
      the inflammatory phase may prevent premature activation of a matrix-synthetic
      contractile phenotype until the wound is cleared, and the infarct
      microenvironment can support mesenchymal cell growth. 

PMID- 24078696
TI  - IL-21 is a double-edged sword in the systemic lupus erythematosus-like disease of
      BXSB.Yaa mice.
AB  - The pleiotropic cytokine IL-21 is implicated in the pathogenesis of human
      systemic lupus erythematosus by polymorphisms in the molecule and its receptor
      (IL-21R). The systemic lupus erythematosus-like autoimmune disease of BXSB.Yaa
      mice is critically dependent on IL-21 signaling, providing a model for
      understanding IL-21/IL-21R signaling in lupus pathogenesis. In this study, we
      generated BXSB.Yaa mice selectively deficient in IL-21R on B cells, on all T
      cells, or on CD8(+) T cells alone and examined the effects on disease. We found
      that IL-21 signaling to B cells is essential for the development of all classical
      disease manifestations, but that IL-21 signaling also supports the expansion of
      central memory, CD8(+) suppressor cells and broadly represses the cytokine
      activity of CD4(+) T cells. These results indicate that IL-21 has both disease
      promoting and disease-suppressive effects in the autoimmune disease of BXSB.Yaa
      mice. 

PMID- 24078697
TI  - Characterization of human afferent lymph dendritic cells from seroma fluids.
AB  - Dendritic cells (DCs) migrate from peripheral tissues to secondary lymphoid
      organs (SLOs) through the afferent lymph. Owing to limitations in investigating
      human lymph, DCs flowing in afferent lymph have not been properly characterized
      in humans until now. In this study, DCs present in seroma, an accrual of human
      afferent lymph occurring after lymph node surgical dissection, were isolated and
      analyzed in detail. Two main DC subsets were identified in seroma that
      corresponded to the migratory DC subsets present in lymph nodes, that is, CD14(+)
      and CD1a(+). The latter also included CD1a(bright) Langerhans cells. The two DC
      subsets appeared to share the same monocytic precursor and to be developmentally
      related; both of them spontaneously released high levels of TGF-beta and
      displayed similar T cell-activating and -polarizing properties. In contrast, they
      differed in the expression of surface molecules, including TLRs; in their
      phagocytic activity; and in the expression of proteins involved in Ag processing
      and presentation. It is worth noting that although both subsets were detected in
      seroma in the postsurgical inflammatory phase, only CD1a(+) DCs migrated via
      afferent lymph under steady-state conditions. In conclusion, the high numbers of
      DCs contained in seroma fluids allowed a proper characterization of human DCs
      migrating via afferent lymph, revealing a continuous stream of DCs from
      peripheral regions toward SLOs under normal conditions. Moreover, we showed that,
      in inflammatory conditions, distinct subsets of DCs can migrate to SLOs via
      afferent lymph. 

PMID- 24078698
TI  - The transcription factor T-bet regulates parasitemia and promotes pathogenesis
      during Plasmodium berghei ANKA murine malaria.
AB  - The pathogenesis of experimental cerebral malaria (ECM) is an immunologic
      process, mediated in part by Th1 CD4(+) T cells. However, the role of the Th1
      CD4(+) T cell differentiation program on the ability to control parasitemia and
      susceptibility to ECM disease during blood stage malaria has never been assessed
      directly. Using the Plasmodium berghei ANKA murine model of ECM and mice
      deficient for the transcription factor T-bet (the master regulator of Th1 cells)
      on the susceptible C57BL/6 background, we demonstrate that although T-bet plays a
      role in the regulation of parasite burden, it also promotes the pathogenesis of
      ECM. T-bet-deficient (Tbx21(-/-)) mice had higher parasitemia than wild type
      controls did during the ECM phase of disease (17.7 +/- 3.1% versus 10.9 +/-
      1.5%). In addition, although 100% (10/10) of wild type mice developed ECM by day
      9 after infection, only 30% (3/10) of Tbx21(-/-) mice succumbed to disease during
      the cerebral phase of infection. Resistance to ECM in Tbx21(-/-) mice was
      associated with diminished numbers of IFN-gamma-producing CD4(+) T cells in the
      spleen and a lower accumulation of CD4(+) and CD8(+) T cells in the brain. An
      augmented Th2 immune response characterized by enhanced production of activated
      GATA-3(+) CD4(+) T cells and elevated levels of the eotaxin, MCP-1, and G-CSF
      cytokines was observed in the absence of T-bet. Our results suggest that in
      virulent malarias, immune modulation or therapy resulting in an early shift
      toward a Th2 response may help to ameliorate the most severe consequences of
      malaria immunopathogenesis and the prospect of host survival. 

PMID- 24078699
TI  - TLR2-induced IL-10 production impairs neutrophil recruitment to infected tissues
      during neonatal bacterial sepsis.
AB  - Sepsis is the third most common cause of neonatal death, with Group B
      Streptococcus (GBS) being the leading bacterial agent. The pathogenesis of
      neonatal septicemia is still unsolved. We described previously that host
      susceptibility to GBS infection is due to early IL-10 production. In this study,
      we investigated whether triggering TLR2 to produce IL-10 is a risk factor for
      neonatal bacterial sepsis. We observed that, in contrast to wild-type (WT) pups,
      neonatal TLR2-deficient mice were resistant to GBS-induced sepsis. Moreover, if
      IL-10 signaling were blocked in WT mice, they also were resistant to sepsis. This
      increased survival rate was due to an efficient recruitment of neutrophils to
      infected tissues that leads to bacterial clearance, thus preventing the
      development of sepsis. To confirm that IL-10 produced through TLR2 activation
      prevents neutrophil recruitment, WT pups were treated with the TLR2 agonist
      Pam3CSK4 prior to nebulization with the neutrophil chemotactic agent LTB4.
      Neutrophil recruitment into the neonatal lungs was inhibited in pups treated with
      Pam3CSK4. However, the migration was restored in Pam3CSK4-treated pups when IL-10
      signaling was blocked (either by anti-IL-10R mAb treatment or by using IL-10
      deficient mice). Our findings highlight that TLR2-induced IL-10 production is a
      key event in neonatal susceptibility to bacterial sepsis. 

PMID- 24078700
TI  - Increased mammalian target of rapamycin complex 2 signaling promotes age-related
      decline in CD4 T cell signaling and function.
AB  - CD4 T cell function declines significantly during aging. Although the mammalian
      target of rapamycin (TOR) has been implicated in aging, the roles of the TOR
      complexes (TORC1, TORC2) in the functional declines of CD4 T cells remain
      unknown. In this study, we demonstrate that aging increases TORC2 signaling in
      murine CD4 T cells, a change blocked by long-term exposure to rapamycin,
      suggesting that functional defects may be the result of enhanced TORC2 function.
      Using overexpression of Rheb to activate TORC1 and Rictor plus Sin1 to augment
      TORC2 in naive CD4 T cells from young mice, we demonstrated that increased TORC2,
      but not TORC1, signaling results in aging-associated biochemical changes.
      Furthermore, elevated TORC2 signaling in naive CD4 T cells from young mice leads
      to in vivo functional declines. The data presented in this article suggest a
      novel model in which aging increases TORC2 signaling and leads to CD4 T cell
      defects in old mice. 

PMID- 24078701
TI  - Selective ablation of lung epithelial IKK2 impairs pulmonary Th17 responses and
      delays the clearance of Pneumocystis.
AB  - Pneumocystis is an atypical fungal pathogen that causes severe, often fatal
      pneumonia in immunocompromised patients. Healthy humans and animals also
      encounter this pathogen, but they generate a protective CD4(+) T cell-dependent
      immune response that clears the pathogen with little evidence of disease.
      Pneumocystis organisms attach tightly to respiratory epithelial cells, and in
      vitro studies have demonstrated that this interaction triggers NF-kappaB
      dependent epithelial cell responses. However, the contribution of respiratory
      epithelial cells to the normal host response to Pneumocystis remains unknown.
      IkappaB kinase 2 (IKK2) is the upstream kinase that is critical for inducible NF
      kappaB activation. To determine whether IKK2-dependent lung epithelial cell (LEC)
      responses contribute to the anti-Pneumocystis immune response in vivo, transgenic
      mice with LEC-specific deletion of IKK2 (IKK2(DeltaLEC)) were generated. Compared
      to wild-type mice, IKK2(DeltaLEC) mice exhibited a delayed onset of Th17 and B
      cell responses in the lung and delayed fungal clearance. Importantly, delayed
      Pneumocystis clearance in IKK2(DeltaLEC) mice was associated with an exacerbated
      immune response, impaired pulmonary function, and altered lung histology. These
      data demonstrate that IKK2-dependent LEC responses are important regulators of
      pulmonary adaptive immune responses and are required for optimal host defense
      against Pneumocystis infection. LECs likely set the threshold for initiation of
      the pulmonary immune response and serve to prevent exacerbated lung inflammation
      by promoting the rapid control of respiratory fungal infection. 

PMID- 24078702
TI  - STAR: an integrated solution to management and visualization of sequencing data.
AB  - MOTIVATION: Easily visualization of complex data features is a necessary step to
      conduct studies on next-generation sequencing (NGS) data. We developed STAR, an
      integrated web application that enables online management, visualization and
      track-based analysis of NGS data. RESULTS: STAR is a multilayer web service
      system. On the client side, STAR leverages JavaScript, HTML5 Canvas and
      asynchronous communications to deliver a smoothly scrolling desktop-like
      graphical user interface with a suite of in-browser analysis tools that range
      from providing simple track configuration controls to sophisticated feature
      detection within datasets. On the server side, STAR supports private session
      state retention via an account management system and provides data management
      modules that enable collection, visualization and analysis of third-party
      sequencing data from the public domain with over thousands of tracks hosted to
      date. Overall, STAR represents a next-generation data exploration solution to
      match the requirements of NGS data, enabling both intuitive visualization and
      dynamic analysis of data. AVAILABILITY AND IMPLEMENTATION: STAR browser system is
      freely available on the web at http://wanglab.ucsd.edu/star/browser and
      https://github.com/angell1117/STAR-genome-browser.

PMID- 24078703
TI  - MS2PIP: a tool for MS/MS peak intensity prediction.
AB  - MOTIVATION: Tandem mass spectrometry provides the means to match mass
      spectrometry signal observations with the chemical entities that generated them.
      The technology produces signal spectra that contain information about the
      chemical dissociation pattern of a peptide that was forced to fragment using
      methods like collision-induced dissociation. The ability to predict these MS(2)
      signals and to understand this fragmentation process is important for sensitive
      high-throughput proteomics research. RESULTS: We present a new tool called
      MS(2)PIP for predicting the intensity of the most important fragment ion signal
      peaks from a peptide sequence. MS(2)PIP pre-processes a large dataset with
      confident peptide-to-spectrum matches to facilitate data-driven model induction
      using a random forest regression learning algorithm. The intensity predictions of
      MS(2)PIP were evaluated on several independent evaluation sets and found to
      correlate significantly better with the observed fragment-ion intensities as
      compared with the current state-of-the-art PeptideART tool. AVAILABILITY:
      MS(2)PIP code is available for both training and predicting at
      http://compomics.com/.

PMID- 24078704
TI  - Optimized atomic statistical potentials: assessment of protein interfaces and
      loops.
AB  - MOTIVATION: Statistical potentials have been widely used for modeling whole
      proteins and their parts (e.g. sidechains and loops) as well as interactions
      between proteins, nucleic acids and small molecules. Here, we formulate the
      statistical potentials entirely within a statistical framework, avoiding
      questionable statistical mechanical assumptions and approximations, including a
      definition of the reference state. RESULTS: We derive a general Bayesian
      framework for inferring statistically optimized atomic potentials (SOAP) in which
      the reference state is replaced with data-driven 'recovery' functions. Moreover,
      we restrain the relative orientation between two covalent bonds instead of a
      simple distance between two atoms, in an effort to capture orientation-dependent
      interactions such as hydrogen bonds. To demonstrate this general approach, we
      computed statistical potentials for protein-protein docking (SOAP-PP) and loop
      modeling (SOAP-Loop). For docking, a near-native model is within the top 10
      scoring models in 40% of the PatchDock benchmark cases, compared with 23 and 27%
      for the state-of-the-art ZDOCK and FireDock scoring functions, respectively.
      Similarly, for modeling 12-residue loops in the PLOP benchmark, the average main
      chain root mean square deviation of the best scored conformations by SOAP-Loop is
      1.5 A, close to the average root mean square deviation of the best sampled
      conformations (1.2 A) and significantly better than that selected by Rosetta (2.1
      A), DFIRE (2.3 A), DOPE (2.5 A) and PLOP scoring functions (3.0 A). Our Bayesian
      framework may also result in more accurate statistical potentials for additional
      modeling applications, thus affording better leverage of the experimentally
      determined protein structures. AVAILABILITY AND IMPLEMENTATION: SOAP-PP and SOAP
      Loop are available as part of MODELLER (http://salilab.org/modeller).

PMID- 24078705
TI  - p66Shc regulates vesicle-mediated secretion in mast cells by affecting F-actin
      dynamics.
AB  - The extracellular vesicular compartment has emerged as a novel system of
      intercellular communication; however, the mechanisms involved in membrane vesicle
      biogenesis and secretion are as yet unclear. Among immune cells releasing
      membrane vesicles-mast cells that reside near tissues exposed to the environment
      are master modulators of immune responses. Here, we have addressed the role of
      p66Shc, a novel regulator of mast cell activation and homeostasis, in the dynamic
      reorganization of the actin cytoskeleton that is associated with morphological
      changes during secretion. We show that p66Shc is recruited as a complex with the
      lipid phosphatase SHIP1 to the F-actin skeleton and impairs antigen-dependent
      cortical F-actin disassembly and membrane ruffling through the inhibition of Vav
      and paxillin phosphorylation. We also show that in addition to acting as a
      negative regulator of antigen-dependent mast cell degranulation, p66Shc limits
      the basal release of granule contents by inhibiting microvesicle budding from the
      plasma membrane and piecemeal degranulation. These findings identify p66Shc as a
      critical regulator of actin dynamics in mast cells, providing a basis for
      understanding the molecular mechanisms involved in vesicle-mediated secretion in
      these cells. 

PMID- 24078706
TI  - That's our policy!

PMID- 24078707
TI  - 1-O-acylceramides are natural components of human and mouse epidermis.
AB  - The lipid-rich stratum corneum functions as a barrier against pathogens and
      desiccation inter alia by an unbroken meshwork of extracellular lipid lamellae.
      These lamellae are composed of cholesterol, fatty acids, and ceramides (Cers) in
      an equimolar ratio. The huge class of skin Cers consists of three groups: group
      I, "classical" long and very long chain Cers; group II, ultra-long chain Cers;
      and group III, omega-esterified ultra-long chain Cers, which are esterified
      either with linoleic acid or with cornified envelope proteins and are required
      for the water permeability barrier. Here, we describe 1-O-acylceramides as a new
      class of epidermal Cers in humans and mice. These Cers contain, in both the N-
      and 1-O-position, long to very long acyl chains. They derive from the group I of
      classical Cers and make up 5% of all esterified Cers. Considering their chemical
      structure and hydrophobicity, we presume 1-O-acylceramides to contribute to the
      water barrier homeostasis. Biosynthesis of 1-O-acylceramides is not dependent on
      lysosomal phospholipase A2. However, glucosylceramide synthase deficiency was
      followed by a 7-fold increase of 1-O-acylceramides, which then contributed 30% to
      all esterified Cers. Furthermore, loss of neutral glucosylceramidase resulted in
      decreased levels of a 1-O-acylceramide subgroup. Therefore, we propose 1-O
      acylceramides to be synthesized at endoplasmic reticulum-related sites. 

PMID- 24078708
TI  - Contrasting metabolic effects of medium- versus long-chain fatty acids in
      skeletal muscle.
AB  - Dietary intake of long-chain fatty acids (LCFAs) plays a causative role in
      insulin resistance and risk of diabetes. Whereas LCFAs promote lipid accumulation
      and insulin resistance, diets rich in medium-chain fatty acids (MCFAs) have been
      associated with increased oxidative metabolism and reduced adiposity, with few
      deleterious effects on insulin action. The molecular mechanisms underlying these
      differences between dietary fat subtypes are poorly understood. To investigate
      this further, we treated C2C12 myotubes with various LCFAs (16:0, 18:1n9, and
      18:2n6) and MCFAs (10:0 and 12:0), as well as fed mice diets rich in LCFAs or
      MCFAs, and investigated fatty acid-induced changes in mitochondrial metabolism
      and oxidative stress. MCFA-treated cells displayed less lipid accumulation,
      increased mitochondrial oxidative capacity, and less oxidative stress than LCFA
      treated cells. These changes were associated with improved insulin action in MCFA
      treated myotubes. MCFA-fed mice exhibited increased energy expenditure, reduced
      adiposity, and better glucose tolerance compared with LCFA-fed mice. Dietary
      MCFAs increased respiration in isolated mitochondria, with a simultaneous
      reduction in reactive oxygen species generation, and subsequently low oxidative
      damage. Collectively our findings indicate that in contrast to LCFAs, MCFAs
      increase the intrinsic respiratory capacity of mitochondria without increasing
      oxidative stress. These effects potentially contribute to the beneficial
      metabolic actions of dietary MCFAs. 

PMID- 24078710
TI  - A user-oriented web crawler for selectively acquiring online content in e-health
      research.
AB  - MOTIVATION: Life stories of diseased and healthy individuals are abundantly
      available on the Internet. Collecting and mining such online content can offer
      many valuable insights into patients' physical and emotional states throughout
      the pre-diagnosis, diagnosis, treatment and post-treatment stages of the disease
      compared with those of healthy subjects. However, such content is widely
      dispersed across the web. Using traditional query-based search engines to
      manually collect relevant materials is rather labor intensive and often
      incomplete due to resource constraints in terms of human query composition and
      result parsing efforts. The alternative option, blindly crawling the whole web,
      has proven inefficient and unaffordable for e-health researchers. RESULTS: We
      propose a user-oriented web crawler that adaptively acquires user-desired content
      on the Internet to meet the specific online data source acquisition needs of e
      health researchers. Experimental results on two cancer-related case studies show
      that the new crawler can substantially accelerate the acquisition of highly
      relevant online content compared with the existing state-of-the-art adaptive web
      crawling technology. For the breast cancer case study using the full training
      set, the new method achieves a cumulative precision between 74.7 and 79.4% after
      5 h of execution till the end of the 20-h long crawling session as compared with
      the cumulative precision between 32.8 and 37.0% using the peer method for the
      same time period. For the lung cancer case study using the full training set, the
      new method achieves a cumulative precision between 56.7 and 61.2% after 5 h of
      execution till the end of the 20-h long crawling session as compared with the
      cumulative precision between 29.3 and 32.4% using the peer method. Using the
      reduced training set in the breast cancer case study, the cumulative precision of
      our method is between 44.6 and 54.9%, whereas the cumulative precision of the
      peer method is between 24.3 and 26.3%; for the lung cancer case study using the
      reduced training set, the cumulative precisions of our method and the peer method
      are, respectively, between 35.7 and 46.7% versus between 24.1 and 29.6%. These
      numbers clearly show a consistently superior accuracy of our method in
      discovering and acquiring user-desired online content for e-health research.
      AVAILABILITY AND IMPLEMENTATION: The implementation of our user-oriented web
      crawler is freely available to non-commercial users via the following Web site:
      http://bsec.ornl.gov/AdaptiveCrawler.shtml. The Web site provides a step-by-step
      guide on how to execute the web crawler implementation. In addition, the Web site
      provides the two study datasets including manually labeled ground truth, initial
      seeds and the crawling results reported in this article.

PMID- 24078709
TI  - Aberrant dolichol chain lengths as biomarkers for retinitis pigmentosa caused by
      impaired dolichol biosynthesis.
AB  - We observed a characteristic shortening of plasma and urinary dolichols in
      retinitis pigmentosa (RP) patients carrying K42E and T206A mutations in the
      dehydrodolichol diphosphate synthase (DHDDS) gene, using liquid chromatography
      mass spectrometry. Dolichol-18 (D18) became the dominant dolichol species in
      patients instead of dolichol-19 (D19) in normal individuals. The D18/D19 ratio
      was calculated and used as an index of dolichol length distribution. K42E/K42E
      and K42E/T206A patients have significantly higher plasma and urinary D18/D19
      ratios than K42E and T206A carriers. The ratios of carriers are significantly
      higher than normal individuals. Receiver operating characteristic (ROC) analysis
      shows that plasma and urinary D18/D19 ratios can unambiguously discriminate
      patients from carriers, and carriers from normal individuals. Dolichol analysis
      also provides evidence that the T206A mutation is RP-causative. The methodologies
      and procedures used for dolichol profiling are reliable, high throughput, and
      cost effective. Dolichol profiling, complementary to genotyping, can be readily
      adapted as a test in the clinic not only for the diagnosis of patients but also
      for identification of carriers with DHDDS or other genetic mutations that may
      impair dolichol biosynthesis. 

PMID- 24078711
TI  - GPCR ontology: development and application of a G protein-coupled receptor
      pharmacology knowledge framework.
AB  - MOTIVATION: Novel tools need to be developed to help scientists analyze large
      amounts of available screening data with the goal to identify entry points for
      the development of novel chemical probes and drugs. As the largest class of drug
      targets, G protein-coupled receptors (GPCRs) remain of particular interest and
      are pursued by numerous academic and industrial research projects. RESULTS: We
      report the first GPCR ontology to facilitate integration and aggregation of GPCR
      targeting drugs and demonstrate its application to classify and analyze a large
      subset of the PubChem database. The GPCR ontology, based on previously reported
      BioAssay Ontology, depicts available pharmacological, biochemical and
      physiological profiles of GPCRs and their ligands. The novelty of the GPCR
      ontology lies in the use of diverse experimental datasets linked by a model to
      formally define these concepts. Using a reasoning system, GPCR ontology offers
      potential for knowledge-based classification of individuals (such as small
      molecules) as a function of the data. AVAILABILITY: The GPCR ontology is
      available at http://www.bioassayontology.org/bao_gpcr and the National Center for
      Biomedical Ontologies Web site.

PMID- 24078712
TI  - BooleSim: an interactive Boolean network simulator.
AB  - SUMMARY: BooleSim (Boolean network simulator) is an open-source in-browser tool
      for simulation and manipulation of Boolean networks. It was developed mainly
      during Google's Summer of Code 2012 and uses the biographer project for network
      visualization. It can be used specifically for the modeling of gene regulatory or
      signal transduction networks. AVAILABILITY AND IMPLEMENTATION: BooleSim is free
      software and can be downloaded from GitHub
      (https://github.com/matthiasbock/BooleSim). Online version available at
      http://rumo.biologie.hu-berlin.de/boolesim/.

PMID- 24078713
TI  - ReportingTools: an automated result processing and presentation toolkit for high
      throughput genomic analyses.
AB  - It is common for computational analyses to generate large amounts of complex data
      that are difficult to process and share with collaborators. Standard methods are
      needed to transform such data into a more useful and intuitive format. We present
      ReportingTools, a Bioconductor package, that automatically recognizes and
      transforms the output of many common Bioconductor packages into rich,
      interactive, HTML-based reports. Reports are not generic, but have been
      individually designed to reflect content specific to the result type detected.
      Tabular output included in reports is sortable, filterable and searchable and
      contains context-relevant hyperlinks to external databases. Additionally, in-line
      graphics have been developed for specific analysis types and are embedded by
      default within table rows, providing a useful visual summary of underlying raw
      data. ReportingTools is highly flexible and reports can be easily customized for
      specific applications using the well-defined API. AVAILABILITY: The
      ReportingTools package is implemented in R and available from Bioconductor
      (version >= 2.11) at the URL:
      http://bioconductor.org/packages/release/bioc/html/ReportingTools.html.
      Installation instructions and usage documentation can also be found at the above
      URL.

PMID- 24078714
TI  - A C library for retrieving specific reactions from the BioModels database.
AB  - SUMMARY: We describe libSBMLReactionFinder, a C library for retrieving specific
      biochemical reactions from the curated systems biology markup language models
      contained in the BioModels database. The library leverages semantic annotations
      in the database to associate reactions with human-readable descriptions, making
      the reactions retrievable through simple string searches. Our goal is to provide
      a useful tool for quantitative modelers who seek to accelerate modeling efforts
      through the reuse of previously published representations of specific chemical
      reactions. AVAILABILITY AND IMPLEMENTATION: The library is open-source and dual
      licensed under the Mozilla Public License Version 2.0 and GNU General Public
      License Version 2.0. Project source code, downloads and documentation are
      available at http://code.google.com/p/lib-sbml-reaction-finder.

PMID- 24078715
TI  - Reporting results from whole-genome and whole-exome sequencing in clinical
      practice: a proposal for Canada?
AB  - PURPOSE: This article proposes recommendations for the use of whole-genome and
      whole-exome (WGS/WES) sequencing in clinical practice, endorsed by the board of
      directors of the Canadian College of Medical Geneticists. The publication of
      statements and recommendations by several international and national
      organisations on clinical WGS/WES has prompted a need for Canadian-specific
      guidance. METHODS: A multi-disciplinary group consisting of lawyers, ethicists,
      genetic researchers, and clinical geneticists was assembled to review existing
      guidelines on WGS/WES and identify provisions relevant to the Canadian context.
      RESULTS: Definitions were provided to orient the recommendations and to minimize
      confusion with other recommendations. Recommendations include the following:
      WGS/WES should be used in a judicious and cost-efficient manner; WGS/WES should
      be used to answer a clinical question; and physicians need to explain to adult
      patients the nature of the results that could arise, so as to allow them to make
      informed choices over whether to take the test and which results they wish to
      receive. Recommendations are also provided for WGS/WES in the pediatric context,
      and for when results implicate patients' family members. CONCLUSION: These
      recommendations are only a proposal to be developed into comprehensive Canadian
      based guidelines. They aim to promote discussion about the reporting of WGS/WES
      results, and to encourage the ethical implementation of these new technologies in
      the clinical setting.

PMID- 24078716
TI  - The cognitive burden of stroke emerges even with an intact NIH Stroke Scale
      Score: a cohort study.
AB  - BACKGROUND: We aim to facilitate recognition of the cognitive burden of stroke by
      describing the parallels between cognitive deficits and the National Institutes
      of Health Stroke Scale (NIHSS), a widely used measure of stroke severity.
      METHODS: A consecutive cohort of 223 working-age patients with an acute first
      ever ischaemic stroke was assessed neuropsychologically within the first weeks
      after stroke and at a 6-months follow-up visit and compared with 50 healthy
      demographic controls. The NIHSS was administered at the time of hospital
      admittance and upon discharge from the acute care unit. The associations between
      total NIHSS scores and domain-specific cognitive deficits were analysed
      correlatively and with a binary logistic regression. RESULTS: Of the NIHSS
      measurements (admittance median=3, range 0-24; discharge median=1, range 0-13),
      the total score at the time of discharge had systematically stronger correlations
      with cognitive impairment. Adjusted for demographics, the NIHSS discharge score
      stably predicted every cognitive deficit with ORs ranging from 1.4 (95% CI 1.2 to
      1.6) for episodic memory to 1.9 (95% CI 1.5 to 2.3) for motor skills. The
      specificities of the models ranged from 89.5-97.7%, but the sensitivities were as
      low as 11.6-47.9%. Cognitive deficits were found in 41% of patients with intact
      NIHSS scores and in all patients with NIHSS scores >=4, a finding that could not
      be accounted for by confounding factors. CONCLUSIONS: Cognitive deficits were
      common even in patients with the lowest NIHSS scores. Thus, low NIHSS scores are
      not effective indicators of good cognitive outcomes after stroke.

PMID- 24078717
TI  - Dopamine agonist withdrawal syndrome (DAWS) in a patient with a
      microprolactinoma.

PMID- 24078718
TI  - Immune reactivity to neurofilament proteins in the clinical staging of
      amyotrophic lateral sclerosis.
AB  - BACKGROUND: Neurofilament (NF) proteins detection in biological fluids as a by
      product of axonal loss is technically challenging and to date relies mostly on
      cerebrospinal fluid (CSF) measurements. Plasma antibodies against NF proteins and
      particularly to their soluble light chain (NF-L) could be a more practical
      surrogate marker for disease staging in amyotrophic lateral sclerosis (ALS), an
      invariably fatal and clinically heterogeneous neuromuscular disorder.
      METHODOLOGY: We have used a recombinant neurofilament light chain (NF-L) protein
      for the ELISA detection of antibodies against NF proteins in plasma samples from
      a well-characterised cohort of ALS individuals (n:73). The use of an established
      functional rating scale and of a recently proposed staging of disease progression
      allowed stratification of the ALS cohort based on disease stage, site of onset,
      survival and speed of disease progression. RESULTS: Antibody levels to NF
      proteins in plasma were significantly higher in ALS individuals compared to
      healthy controls (p<0.001). Higher NF plasma immunoreactivity was seen in
      advanced ALS cases (stage IVA-B) compared to earlier phases of the disease
      (p<0.05). There was no difference in anti-NF plasma antibodies between ALS
      individuals treated with riluzole and untreated patients; although riluzole
      treated ALS cases with an earlier age of onset and with a shorter diagnostic
      delay displayed higher anti-NFL antibody levels compared to untreated ALS
      patients with similar features. CONCLUSIONS: Immunoreactivity to plasma NF-L and
      homologous NF proteins is informative of the stage of disease progression in ALS.
      The determination of NF antibody levels in plasma could be added to the growing
      panel of disease-monitoring biomarkers in ALS targeting cytoskeletal antigens.

PMID- 24078722
TI  - Cell line contamination and misidentification.

PMID- 24078721
TI  - Clinical Cerenkov luminescence imaging of (18)F-FDG.
AB  - The aim of this study was to determine the feasibility of Cerenkov luminescence
      (CL) imaging of patients undergoing diagnostic (18)F-FDG scans to detect nodal
      disease. METHODS: Patients undergoing routine (18)F-FDG PET/CT for various
      malignancies consented to being scanned for CL. White-light and Cerenkov images
      (5-min acquisition) of the surface of the patient contralateral to and at the
      site of nodal (18)F-FDG uptake were acquired using a cooled, intensified charge
      coupled-device camera. RESULTS: The camera demonstrated linear correlation
      between activity and counts into the low nanocurie range using (18)F-FDG. Imaging
      of patients revealed the presence of (18)F-FDG uptake in nodes that demonstrated
      uptake on PET. A correlation between maximum standardized uptake value from PET
      and counting rate per area on the CL imaging was established. CONCLUSION: CL
      imaging with diagnostic doses of (18)F-FDG is feasible and can aid in detecting
      disease in the clinical setting.

PMID- 24078723
TI  - Hemorrhagic stroke: the broad horizon of aneurysm treatment.

PMID- 24078724
TI  - Discrimination in the UK's postgraduate examination in primary care.

PMID- 24078725
TI  - GPs' income has fallen 16% in real terms since 2004-05.

PMID- 24078726
TI  - Competition is holding back quality improvements, says NHS boss.

PMID- 24078727
TI  - Turkish police targeted doctors who helped protesters, report says.

PMID- 24078728
TI  - BMJ author hits out at attempts to dismiss findings of possible racial bias in
      RCGP exam.

PMID- 24078729
TI  - NICE guidelines urge local authorities to "spend to save" on public health.

PMID- 24078730
TI  - Scientists say they are 95% certain that humanity is responsible for climate
      change.

PMID- 24078731
TI  - Abeta-related angiitis: comparison with CAA without inflammation and primary CNS
      vasculitis.
AB  - OBJECTIVE: To analyze the clinical findings, response to therapy, and outcomes of
      patients with cerebral vascular amyloid-beta (Abeta) deposition with and without
      inflammatory vascular infiltration. METHODS: We report 78 consecutive patients
      with cerebral vascular Abeta deposition examined at Mayo Clinic Rochester over 25
      years (1987 through 2011). Specimens reviewed by a neuropathologist showed 40
      with vascular Abeta peptide without inflammation (cerebral amyloid angiopathy
      [CAA]), 28 with granulomatous vasculitis (Abeta-related angiitis or ABRA), and 10
      with perivascular CAA-related inflammation. We also matched findings in 118
      consecutive patients with primary CNS vasculitis (PCNSV) without Abeta seen over
      25 years (1983 through 2007). RESULTS: Compared to the 40 with CAA, the 28 with
      ABRA were younger at diagnosis (p = 0.05), had less altered cognition (p = 0.02),
      fewer neurologic deficits (p = 0.02), and fewer intracranial hemorrhages
      (<0.001), but increased gadolinium leptomeningeal enhancement (p = 0.01) at
      presentation, and less mortality and disability at last follow-up (p < 0.001).
      Compared with PCNSV, the 28 patients with ABRA were older at diagnosis (p <
      0.001), had a higher frequency of altered cognition (p = 0.05), seizures/spells
      (p = 0.006), gadolinium leptomeningeal enhancement (p < 0.001), and intracerebral
      hemorrhage (p = 0.02), lower frequency of hemiparesis (p = 0.01), visual symptoms
      (p = 0.04), and MRI evidence of cerebral infarction (p = 0.003), but higher CSF
      protein levels (p = 0.03). Results of treatment and outcomes in ABRA and PCNSV
      were similar. CONCLUSIONS: ABRA appears to represent a distinct subset of PCNSV.

PMID- 24078733
TI  - Fitness, depression, and poststroke fatigue: worn out or weary?
AB  - Each year, around 15 million people worldwide have a stroke. Of these, at least 5
      million die, a third remain disabled, and the remainder make a good recovery.(1)
      Yet more than half of all these 10 million survivors will have fatigue, one of
      the most debilitating, but least studied, poststroke symptoms. Poststroke fatigue
      (PSF) is a multifaceted phenomenon.(2) It has been correlated with lowered mood,
      as well as being influenced by other factors, like age, sex, and cognition. Many
      researchers have demonstrated that the presence of fatigue negatively influences
      quality of life, return to work, and perhaps mortality.(3,4) However, most
      studies have been conducted cross-sectionally, in the subacute or chronic phase
      after stroke.(4-6.) 

PMID- 24078732
TI  - Charcot-Marie-Tooth disease: genetic and clinical spectrum in a Spanish clinical
      series.
AB  - OBJECTIVES: To determine the genetic distribution and the phenotypic correlation
      of an extensive series of patients with Charcot-Marie-Tooth disease in a
      geographically well-defined Mediterranean area. METHODS: A thorough genetic
      screening, including most of the known genes involved in this disease, was
      performed and analyzed in this longitudinal descriptive study. Clinical data were
      analyzed and compared among the genetic subgroups. RESULTS: Molecular diagnosis
      was accomplished in 365 of 438 patients (83.3%), with a higher success rate in
      demyelinating forms of the disease. The CMT1A duplication (PMP22 gene) was the
      most frequent genetic diagnosis (50.4%), followed by mutations in the GJB1 gene
      (15.3%), and in the GDAP1 gene (11.5%). Mutations in 13 other genes were
      identified, but were much less frequent. Sixteen novel mutations were detected
      and characterized phenotypically. CONCLUSIONS: The relatively high frequency of
      GDAP1 mutations, coupled with the scarceness of MFN2 mutations (1.1%) and the
      high proportion of recessive inheritance (11.6%) in this series exemplify the
      particularity of the genetic distribution of Charcot-Marie-Tooth disease in this
      region.

PMID- 24078734
TI  - Fatigue in the acute phase after first stroke predicts poorer physical health 18
      months later.
AB  - OBJECTIVE: To determine whether fatigue in the acute phase following stroke
      predicts long-term patient-reported physical and mental health outcomes 18 months
      later. METHODS: Patients (n = 96, mean age 67.8 years, SD 12.9) were assessed
      within 2 weeks of hospital admission for first-ever stroke (acute phase) and 18
      months later. Measures included the Fatigue Severity Scale and the Beck
      Depression Inventory II. The Short Form-36 was used to assess self-reported
      physical and mental health. Multivariate regression analysis was used to evaluate
      the relationship between acute phase fatigue and later health outcomes,
      controlling for relevant covariates. RESULTS: Acute phase fatigue was associated
      with physical health at 18-month follow-up, but not with mental health. After
      adjusting for other potential predictors of health outcomes, including age, sex,
      cohabitation status, acute phase physical or mental health, and depressive
      symptoms, acute phase fatigue remained a significant predictor of later physical
      health but not of later mental health. The reverse relationships were also
      examined, but neither physical nor mental health in the acute phase predicted
      fatigue at 18 months; the best predictor of fatigue at 18-month follow-up was
      acute phase fatigue. CONCLUSIONS: These findings suggest that acute phase fatigue
      is an independent risk factor for poor physical health 18 months after stroke.
      Diagnosis and treatment of acute phase fatigue may improve physical health
      related quality of life among stroke survivors. Effective treatments for
      poststroke fatigue, both in the acute phase and later in the recovery period, are
      needed.

PMID- 24078736
TI  - Adult neurogenesis in the dentate gyrus: general concepts and potential
      implications.

PMID- 24078735
TI  - Gait speed in Parkinson disease correlates with cholinergic degeneration.
AB  - OBJECTIVE: We investigated dopaminergic and cholinergic correlates of gait speed
      in Parkinson disease (PD) and non-PD control subjects to test the hypothesis that
      gait dysfunction in PD may result from multisystem degeneration. METHODS: This
      was a cross-sectional study. Subjects with PD but without dementia (n = 125, age
      65.6 +/- 7.3 years) and elderly subjects without PD (n = 32, age 66.0 +/- 10.6
      years) underwent [11C]dihydrotetrabenazine dopaminergic and [(11)C]methyl-4
      piperidinyl propionate acetylcholinesterase PET imaging, and cognitive and
      clinical testing, including an 8.5-m walk in the dopaminergic "off" state. The
      fifth percentile of cortical cholinergic activity in the elderly without PD was
      used to define normal-range activity in the subjects with PD. RESULTS: Normal
      range cortical cholinergic activity was present in 87 subjects with PD (69.6%).
      Analysis of covariance using gait speed as the dependent variable demonstrated a
      significant model (F = 6.70, p < 0.0001) with a significant group effect (F =
      3.36, p = 0.037) and significant slower gait speed in the low cholinergic PD
      subgroup (0.97 +/- 0.22 m/s) with no significant difference between the normal
      range cholinergic PD subgroup (1.12 +/- 0.20 m/s) and control subjects (1.17 +/-
      0.18 m/s). Covariate effects were significant for cognition (F = 6.58, p =
      0.011), but not for striatal dopaminergic innervation, sex, or age. CONCLUSION:
      Comorbid cortical cholinergic denervation is a more robust marker of slowing of
      gait in PD than nigrostriatal denervation alone. Gait speed is not significantly
      slower than normal in subjects with PD with relatively isolated nigrostriatal
      denervation.

PMID- 24078737
TI  - Deletions in GRID2 lead to a recessive syndrome of cerebellar ataxia and tonic
      upgaze in humans.
AB  - OBJECTIVE: To identify the genetic cause of a syndrome causing cerebellar ataxia
      and eye movement abnormalities. METHODS: We identified 2 families with cerebellar
      ataxia, eye movement abnormalities, and global developmental delay. We performed
      genetic analyses including single nucleotide polymorphism genotyping, linkage
      analysis, array comparative genomic hybridization, quantitative PCR, and Sanger
      sequencing. We obtained eye movement recordings of mutant mice deficient for the
      ortholog of the identified candidate gene, and performed immunohistochemistry
      using human and mouse brain specimens. RESULTS: All affected individuals had
      ataxia, eye movement abnormalities, most notably tonic upgaze, and delayed speech
      and cognitive development. Homozygosity mapping identified the disease locus on
      chromosome 4q. Within this region, a homozygous deletion of GRID2 exon 4 in the
      index family and compound heterozygous deletions involving GRID2 exon 2 in the
      second family were identified. Grid2-deficient mice showed larger spontaneous and
      random eye movements compared to wild-type mice. In developing mouse and human
      cerebella, GRID2 localized to the Purkinje cell dendritic spines. Brain MRI in 2
      affected children showed progressive cerebellar atrophy, which was more severe
      than that of Grid2-deficient mice. CONCLUSIONS: Biallelic deletions of GRID2 lead
      to a syndrome of cerebellar ataxia and tonic upgaze in humans. The phenotypic
      resemblance and similarity in protein expression pattern between humans and mice
      suggest a conserved role for GRID2 in the synapse organization between parallel
      fibers and Purkinje cells. However, the progressive and severe cerebellar atrophy
      seen in the affected individuals could indicate an evolutionarily unique role for
      GRID2 in the human cerebellum.

PMID- 24078739
TI  - Micro-TLC Approach for Fast Screening of Environmental Samples Derived from
      Surface and Sewage Waters.
AB  - In this work we demonstrated analytical capability of micro-planar (micro-TLC)
      technique comprising one and two-dimensional (2D) separation modes to generate
      fingerprints of environmental samples originated from sewage and ecosystems
      waters. We showed that elaborated separation and detection protocols are
      complementary to previously invented HPLC method based on temperature-dependent
      inclusion chromatography and UV-DAD detection. Presented 1D and 2D micro-TLC
      chromatograms of SPE (solid-phase extraction) extracts were optimized for fast
      and low-cost screening of water samples collected from lakes and rivers located
      in the area of Middle Pomerania in northern part of Poland. Moreover, we studied
      highly organic compounds loaded in the treated and untreated sewage waters
      obtained from municipal wastewater treatment plant "Jamno" near Koszalin City
      (Poland). Analyzed environmental samples contained number of substances
      characterized by polarity range from estetrol to progesterone as well as
      chlorophyll-related dyes previously isolated and pre-purified by simple SPE
      protocol involving C18 cartridges. Optimization of micro-TLC separation and
      quantification protocols of such samples were discussed from the practical point
      of view using simple separation efficiency criteria including total peaks number,
      log(product DeltahRF), signal intensity and peak asymmetry. Outcomes of the
      presented analytical approach, especially using detection involving direct
      fluorescence (UV366/Vis) and phosphomolybdic acid (PMA) visualization are
      compared with UV-DAD HPLC-generated data reported previously. Chemometric
      investigation based on principal components analysis revealed that SPE extracts
      separated by micro-TLC and detected under fluorescence and PMA visualization
      modes can be used for robust sample fingerprinting even after long-term storage
      of the extracts (up to 4 years) at subambient temperature (-20  degrees C). Such
      approach allows characterization of wide range of sample components that are
      present in given extract in high and middle concentration range. Due to protocol
      simplicity and low cost of analysis this method can be useful for preliminary
      sample screening.

PMID- 24078740
TI  - A Modified Device for Pressurized Planar Electrochromatography and Preliminary
      Results with On-Line Sample Application.
AB  - Pressurized planar electrochromatography (PPEC) is a separating technique in
      which an electric field is applied to force the mobile phase movement through a
      porous media (electroosmotic effect). High separation efficiency, fast
      separations and changes in separation selectivity in comparison to liquid
      chromatography, especially thin layer chromatography (planar chromatography,
      TLC), are features of this technique. Constructional methodological challenges to
      PPEC are obstacles to its development and application in laboratory practice. In
      this article, an attempt to overcome the challenges related to device
      construction and sample application/injection is described. The introduced device
      enables both prewetting of the adsorbent layer and electrochromatogram
      development with a single PPEC device. It also enables simultaneous
      application/injection of six samples on a chromatographic plate in a stream of
      the mobile phase (on-line application/injection). In addition, the PPEC chamber
      was equipped with a thermostat. The device is characterized by an impressive
      throughput in comparison to the other planar technique, TLC/HPTLC. Although the
      developed device still needs improvement, it is, in our opinion, a considerable
      step toward possible automation of this planar separation technique.

PMID- 24078738
TI  - Microfluidic Paper-Based Analytical Devices (MUPADs) and Micro Total Analysis
      Systems (MUTAS): Development, Applications and Future Trends.
AB  - Microfluidic paper-based analytical devices and micro total analysis systems are
      relatively new group of analytical tools, capable of analyzing complex
      biochemical samples containing macromolecules, proteins, nucleic acids, toxins,
      cells or pathogens. Within one analytical run, fluidic manipulations like
      transportation, sorting, mixing or separation are available. Recently,
      microfluidic devices are a subject of extensive research, mostly for fast and non
      expensive biochemical analysis but also for screening of medical samples and
      forensic diagnostics. They are used for neurotransmitter detection, cancer
      diagnosis and treatment, cell and tissue culture growth and amplification, drug
      discovery and determination, detection and identification of microorganisms. This
      review summarizes development history, basic fabrication methods, applications
      and also future development trends for production of such devices.

PMID- 24078741
TI  - Comparison of TLC and Different Micro TLC Techniques in Analysis of Tropane
      Alkaloids and Their Derivatives Mixture from Datura Inoxia Mill. Extract.
AB  - Planar chromatography is a very useful tool for analysis of wide range of
      different mixtures. Thanks to its possibility for rapid separation of large
      number of samples simultaneously, low solvent consumption and ability to analyse
      rough material allow to receive precise and reliable results in short time and
      low cost. Miniaturization of planar techniques brings a lot of advantages, such
      as shortening distance and time of chromatogram development, and further lowering
      of solvent consumption. Besides, it often allows to improve separation parameters
      and raise efficiency of chromatographic system. In this paper, ability of
      analysis of tropane alkaloids mixture from Datura Inoxia Mill. extract using
      conventional TLC technique with five micro TLC techniques (short distance TLC,
      HPTLC, UTLC, OPLC and ETLC) in maximally closed chromatographic conditions was
      compared in order to present abilities of micro TLC techniques in plant material
      analysis.

PMID- 24078742
TI  - Micro 2D-TLC of Selected Plant Extracts in Screening of Their Composition and
      Antioxidative Properties.
AB  - Micro two-dimensional separations were performed on polar bonded stationary
      phases of the type cyanopropyl-silica using non-aqueous eluents (polar modifier
      dissolved in n-heptane) as the first direction eluents and aqueous eluents
      (organic modifier-MeOH dissolved in water) as the second direction eluents. The
      chromatographic process was performed in micro scale using 5 * 5 cm plates, small
      volumes of eluents and 10 MUL of plant extracts to obtain satisfying separation.
      Plates developed in horizontal chambers were dried and observed in UV light (254
      nm and 366 m) photographed by digital camera and derivatized by DPPH to detect
      antioxidants (free radical scavengers) or derivatized by Naturstoff reagent to
      detect phenolic compounds (characteristic luminescence of some phenolic
      compounds). The above experiments give the possibility to construct fingerprints
      for investigated Polygonum hydropiper, Betula verrucosa and Pulmonaria
      officinalis extracts. It can be used in quality control of the plant material and
      its antioxidative activity. Novelty of the paper is the micro-scale of the
      separation by two-dimensional thin layer chromatography mode. For the first time
      two-dimensional separation of plant extracts on 5 * 5 cm plates in two directions
      is performed.

PMID- 24078743
TI  - Academic Achievement and Loneliness of Migrant Children in China: School
      Segregation and Segmented Assimilation.
AB  - China's rural-urban migration presents a significant educational challenge. This
      study uses theories of segmented assimilation and school segregation to measure
      the assimilation and well-being of migrant children who attend either Beijing's
      public schools or its informal migrant schools. Controling for other factors, we
      find poorer achievement and greater loneliness among migrant children who are
      isolated in migrant schools than similar migrant students enrolled in regular
      urban public schools. We show there is little difference in learning outcome or
      loneliness between urban native children and migrant children who attend public
      schools. We further discuss similarities and differences between the experiences
      of migrant children in China and immigrant children in the United States.

PMID- 24078744
TI  - Design Optimization of a TOF, Breast PET Scanner.
AB  - A dedicated breast positron emission tomography (PET) scanner with limited angle
      geometry can provide flexibility in detector placement around the patient as well
      as the ability to combine it with other imaging modalities. A primary challenge
      of a stationary limited angle scanner is the reduced image quality due to
      artifacts present in the reconstructed image leading to a loss in quantitative
      information. Previously it has been shown that using time-of-flight (TOF)
      information in image reconstruction can help reduce these image artifacts arising
      due to missing angular projections. Our goal in this work is to optimize the TOF,
      breast scanner design by performing studies for estimating image uniformity and
      lesion activity uptake as a function of system timing resolution, scanner angular
      coverage and shape. Our results show that (i) 1.5 * 1.5 * 15 mm3 lutetium oxy
      orthosilicate (LSO) crystals provide a high spatial resolution and system
      sensitivity relative to clinical scanners, (ii) 2/3 angular coverage scanner
      design with TOF timing resolution less than 600 ps is appropriate for providing a
      tomographic image with fewer artifacts and good lesion uptake estimation relative
      to other partial ring designs studied in this work, (iii) a flat scanner design
      with 2/3 angular coverage is affected more by larger parallax error than a curved
      scanner geometry with the same angular coverage, but provides more uniform lesion
      contrast estimate over the imaging field-of-view (FOV), (iv) 2/3 angular
      coverage, flat, 300 ps TOF scanner design (for short, practical scan times of <=
      5 mins per breast) provides similar precision of contrast recovery coefficient
      (CRC) values to a full curved, non-TOF scanner, and (v) employing depth-of
      interaction (DOI) measuring detector and/or implementing resolution modeling (RM)
      in image reconstruction lead to improved and more uniform spatial resolution and
      lesion contrast over the whole FOV.

PMID- 24078745
TI  - Using Peer Injunctive Norms to Predict Early Adolescent Cigarette Smoking
      Intentions.
AB  - The present study investigated the importance of the perceived injunctive norm to
      predict early adolescent cigarette smoking intentions. A total of 271 6th graders
      completed a survey that included perceived prevalence of friend smoking
      (descriptive norm), perceptions of friends' disapproval of smoking (injunctive
      norm), and future smoking intentions. Participants also listed their five best
      friends, in which the actual injunctive norm was calculated. Results showed that
      smoking intentions were significantly correlated with the perceived injunctive
      norm but not with the actual injunctive norm. Secondly, the perceived injunctive
      norm predicted an additional 3.4% of variance in smoking intentions above and
      beyond the perceived descriptive norm. These results demonstrate the importance
      of the perceived injunctive norm in predicting early adolescent smoking
      intentions.

PMID- 24078746
TI  - Trajectories of Delinquency among Puerto Rican Children and Adolescents at Two
      Sites.
AB  - This study examined the trajectories of delinquency among Puerto Rican children
      and adolescents in two cultural contexts. Relying on data from the Boricua Youth
      Study, a longitudinal study of children and youth from Bronx, New York, and San
      Juan, Puerto Rico, a group-based trajectory procedure estimated the number of
      delinquency trajectories, whether trajectories differed across contexts, and the
      relation of risk and protective factors to each. Five trajectories fit the Bronx
      sample, and four fit the San Juan sample. Differences and similarities were
      observed. The Bronx sample had a higher rate of delinquency and sensation seeking
      and violence exposure strongly discriminated offender trajectories. In San Juan,
      the results were substantively the same. Thus, while the youth lived in different
      contexts, and the nature and level of delinquency varied across the sites, the
      effects of most risk factors were more similar than different.

PMID- 24078747
TI  - Comparative study on coating CdSe nanocrystals with surfactants.
AB  - We have synthesized CdSe nanocrystals (NCs) in sizes from 2.2 to 5.1 nm
      passivated with hydrophobic trioctylphosphine oxide (TOPO) in combination
      trioctylphosphine (TOP) or tributylphosphine (TBP) to obtain particles of the
      type CdSe/TOPO/TOP or CdSe/TOPO/TBP. These NCs were then dispersed in aqueous
      solution of ionic or non-ionic surfactants (such as stearate, oleic acid, Tween)
      using a biphase (water and chloroform or hexane) transfer method. It is found
      that both the structure of the surfactant and the native surface of the ligand
      govern the coating of the NCs with surfactants. More specifically, the
      hydrophobicity-hydrophilicity balance of the surfactant regulates the coating
      efficacy, thereby transferring the NC from the organic to the aqueous phase. The
      type of ligand on the NCs and the kind of coating surfactant also affect
      photoluminescence (PL). The ratio of PL and absorbance unit (defined as PL per
      0.1 AU) was implemented as a tool to monitor changes in PL intensity and
      wavelength as a function of size, coatings and surface defects. Finally, the
      distribution of CdSe nanocrystals between pseudophases in cloud point extraction
      was discussed based on experimental results. It was concluded that the size of
      CdSe nanocrystal present in an appropriate pseudophase is correlated with the way
      in which the non-ionic surfactant coats CdSe nanocrystals. FigureCoating of CdSe
      semiconductor nanocrystals with surfactants impacts nanocrystals' spectral
      features. Absorbance of first exciton absorption band was used to estimate
      ability of surfactant to disperse CdSe nanocrystals. Photoluminescence (PL)
      intensity and position of PL band were analysed in terms of nanocrystal's surface
      phenomena via surfactants applied for coating.

PMID- 24078748
TI  - An efficient and cost-effective preparation of di-O-acetyl-D-rhamnal.
AB  - We have developed a synthetic route to the frequently utilized deoxysugar
      building block di-O-acetyl-D-rhamnal originating from the inexpensive starting
      material methyl alpha-D-glucopyranoside. Our approach proceeds in five steps with
      minimal column chromatography purification needed to afford the title compound in
      good overall yield. 2009 Elsevier Ltd. All rights reserved.

PMID- 24078750
TI  - Correction.

PMID- 24078749
TI  - Changing patterns of cytomegalovirus seroprevalence among pregnant women in
      Norway between 1995 and 2009 examined in the Norwegian Mother and Child Cohort
      Study and two cohorts from Sor-Trondelag County: a cross-sectional study.
AB  - OBJECTIVES: To examine cytomegalovirus (CMV) seroprevalence and associated risk
      factors for CMV seropositivity in pregnant Norwegian women. DESIGN: Cross
      sectional study. SETTING: The Norwegian Mother and Child Cohort Study (MoBa) in
      addition to two random samples of pregnant women from Sor-Trondelag County in
      Norway. PARTICIPANTS: Study group 1 were 1000 pregnant women, randomly selected
      among 46 127 pregnancies in the MoBa (1999-2006) at 17/18 week of gestation. Non
      ethnic Norwegian women were excluded. Study groups 2 (n=1013 from 1995) and 3
      (n=979 from 2009) were pregnant women at 12 weeks of gestation from Sor-Trondelag
      County. OUTCOME MEASURES: CMV seropositivity in blood samples from pregnant
      Norwegian women. RESULTS: CMV-IgG antibodies were detected in 59.9% and CMV-IgM
      antibodies in 1.3% of pregnant Norwegian women in study group 1. Women from North
      Norway demonstrated a higher CMV-IgG seroprevalence (72.1%) than women from South
      Norway (58.5%) (OR 1.83, 95% CI 1.17 to 2.88). The CMV-IgG seroprevalence was
      higher among women with low education (70.5%) compared to women with higher
      education (OR 2.20, 95% CI 1.24 to 3.90). Between 1995 and 2009 the CMV-IgG
      seroprevalence increased from 63.1% to 71.4% in pregnant women from Sor-Trondelag
      County (study groups 2 and 3; p<0.001). The highest CMV-IgG seroprevalence
      (79.0%) was observed among the youngest pregnant women (<25 years) from Sor
      Trondelag County in 2009 (study group 3). CONCLUSIONS: The CMV-IgG seroprevalence
      of pregnant Norwegian women varies with geographic location and educational
      level. Additionally, the CMV-IgG seroprevalence appears to have increased over
      the last years, particularly among young pregnant women.

PMID- 24078751
TI  - Patient safety and estimation of renal function in patients prescribed new oral
      anticoagulants for stroke prevention in atrial fibrillation: a cross-sectional
      study.
AB  - OBJECTIVE: In clinical trials of dabigatran and rivaroxaban for stroke prevention
      in atrial fibrillation (AF), drug eligibility and dosing were determined using
      the Cockcroft-Gault equation to estimate creatine clearance as a measure of renal
      function. This cross-sectional study aimed to compare whether using estimated
      glomerular filtration rate (eGFR) by the widely available and widely used
      Modified Diet in Renal Disease (MDRD) equation would alter prescribing or dosing
      of the renally excreted new oral anticoagulants. PARTICIPANTS: Of 4712 patients
      with known AF within a general practitioner-registered population of 930 079 in
      east London, data were available enabling renal function to be calculated by both
      Cockcroft-Gault and MDRD methods in 4120 (87.4%). RESULTS: Of 4120 patients, 2706
      were <80 years and 1414 were >=80 years of age. Among those >=80 years, 14.9%
      were ineligible for dabigatran according to Cockcroft-Gault equation but would
      have been judged eligible applying MDRD method. For those <80 years, 0.8% would
      have been incorrectly judged eligible for dabigatran and 5.3% would have received
      too high a dose. For rivaroxaban, 0.3% would have been incorrectly judged
      eligible for treatment and 13.5% would have received too high a dose.
      CONCLUSIONS: Were the MDRD-derived eGFR to be used instead of Cockcroft-Gault in
      prescribing these new agents, many elderly patients with AF would either
      incorrectly become eligible for them or would receive too high a dose. Safety has
      not been established using the MDRD equation, a concern since the risk of major
      bleeding would be increased in patients with unsuspected renal impairment. Given
      the potentially widespread use of these agents, particularly in primary care,
      regulatory authorities and drug companies should alert UK doctors of the need to
      use the Cockcroft-Gault formula to calculate eligibility for and dosing of the
      new oral anticoagulants in elderly patients with AF and not rely on the MDRD
      derived eGFR.

PMID- 24078752
TI  - Reporting of harms data in RCTs: a systematic review of empirical assessments
      against the CONSORT harms extension.
AB  - OBJECTIVE: To determine the standard of reporting of harms-related data, in
      randomised controlled trials (RCTs) according to the Consolidated Standards of
      Reporting Trials (CONSORT) statement extension for harms. DESIGN: Systematic
      review. DATA SOURCES: The Cochrane library, Ovid MEDLINE, Scopus and ISI Web of
      Knowledge were searched for relevant literature. ELIGIBILITY CRITERIA FOR
      SELECTING STUDIES: We included publications of studies that used the CONSORT
      harms extension to assess the reporting of harms in RCTs. RESULTS: We identified
      7 studies which included between 10 and 205 RCTs. The clinical areas of the 7
      studies were: hypertension (1), urology (1), epilepsy (1), complimentary medicine
      (2) and two not restricted to a clinical topic. Quality of the 7 studies was
      assessed by a risk of bias tool and was found to be variable. Adherence to the
      CONSORT harms criteria reported in the 7 studies was inadequate and variable
      across the items in the checklist. Adverse events are poorly defined, with 6
      studies failing to exceed 50% adherence to the items in the checklist.
      CONCLUSIONS: Readers of RCT publications need to be able to balance the trade
      offs between benefits and harms of interventions. This systematic review suggests
      that this is compromised due to poor reporting of harms which is evident across a
      range of clinical areas. Improvements in quality could be achieved by wider
      adoption of the CONSORT harms criteria by journals reporting RCTs.

PMID- 24078753
TI  - A qualitative study of patients' perceptions and priorities when living with
      primary frozen shoulder.
AB  - OBJECTIVES: To elucidate the experiences and perceptions of people living with
      primary frozen shoulder and their priorities for treatment. DESIGN: Qualitative
      study design using semistructured interviews. SETTING: General practitioner (GP)
      and musculoskeletal clinics in primary and secondary care in one National Health
      Service Trust in England. PARTICIPANTS: 12 patients diagnosed with primary frozen
      shoulder were purposively recruited from a GP's surgery, community clinics and
      hospital clinics. Recruitment targeted the phases of frozen shoulder: pain
      predominant (n=5), stiffness predominant (n=4) and residual stiffness predominant
      following hospital treatment (n=2). One participant dropped out. INCLUSION
      CRITERIA: adult, male and female patients of any age, attending the clinics, who
      had been diagnosed with primary frozen shoulder. RESULTS: The most important
      experiential themes identified by participants were: pain which was severe as
      well as inexplicable; inconvenience/disability arising from increasing
      restriction of movement (due to pain initially, gradually giving way to
      stiffness); confusion/anxiety associated with delay in diagnosis and uncertainty
      about the implications for the future; and treatment-related aspects.
      Participants not directly referred to a specialist (whether physiotherapist,
      physician or surgeon) wanted a faster, better-defined care pathway. Specialist
      consultation brought more definitive diagnosis, relief from anxiety and usually
      self-rated improvement. The main treatment priority was improved function, though
      there was recognition that this might be facilitated by relief of pain or
      stiffness. There was a general lack of information from clinicians about the
      condition with over-reliance on verbal communication and very little written
      information. CONCLUSIONS: Awareness of frozen shoulder should be increased among
      non-specialists and the best available information made accessible for patients.
      Our results also highlight the importance of patient participation in frozen
      shoulder research.

PMID- 24078754
TI  - Method Development for the Determination of Diallyldimethylammonium Chloride at
      Trace Levels by Epoxidation Process.
AB  - Domestic water is abstracted from its sources in raw form with a high content of
      dissolved and suspended material. Polydiallyldimethylammonium chloride
      (polyDADMAC) is a cationic polyelectrolyte used in the initial water
      clarification process. However, its residues in treated water pose a health risk
      as they react with chlorine to produce a carcinogenic compound. There is a need
      to determine the concentration of the polyelectrolyte cations that pass through
      the flocculation stage before the chlorine disinfection process in water
      treatment plants to ascertain the safety of water to consumers. The cationic
      polymer is UV inactive, and previously available methods for determining the
      concentrations of polyelectrolytes are unsatisfactory due to poor detection
      limits. This paper describes a UV-Visible (UV-vis) spectrophotometry method for
      the determination of residual polyDADMAC as an epoxide. The novelty method lies
      on the epoxidation of polyDADMAC using 20 % sodium hydroxide dissolved in 30 %
      hydrogen peroxide to produce a UV-Vis active compound. The epoxidation was
      confirmed by UV-Vis, FTIR and 1H NMR techniques. Dilute solutions of varying
      concentrations of polyDADMAC (0.2-1.0 mg L-1) were treated with a basic solution
      of hydrogen peroxide then analysed by UV-Vis spectrophotometry. The wavelength at
      maximum absorption (lambdamax) was found to be 313 nm, and a linear calibration
      curve with a correlation coefficient (R2) of 0.993 was used for quantification
      purposes. The detection limit measured as three times the signal of the blank and
      was found to be 2.1 * 10-4 mg L-1. The method was applied to determine the
      concentration of polyDADMAC spiked in water samples collected from a pool as a
      model for environmental matrix. The results obtained agreed with the quantities
      spiked in the solution, thus qualified the method to be suitable for the
      determination of polyDADMAC in treated waters at trace levels. The method was
      also used to investigate the adsorption capacity of polyDADMAC on sand filters.
      The adsorption method was found to be in accordance with Langmuir with an
      adsorption capacity of 2.068 mg g-1.

PMID- 24078755
TI  - Electrochemical, Photochemical, and Photoelectrochemical Treatment of Sodium p 
      Cumenesulfonate.
AB  - The degradation of sodium p-cumenesulfonate (SCS) by electrochemical,
      photochemical, and photoelectrochemical methods in aqueous solution of NaClO4,
      NaCl, and NaClO has been studied. It was found that as a result of NaClO4
      electroreduction and photodecomposition, the ions Cl- and ClO3- are formed. These
      ions undergo transformations into radicals, mainly Cl*, Cl2*-, ClO*-, ClO2*-, and
      ClO3*-, due to electrochemical and photochemical reactions. It was shown that the
      interpretation of results of the studies over mineralization processes carried
      out in the presence of ClO4- cannot be adequate without taking into consideration
      the reduction of ClO4- to Cl- and ClO3-. Therefore, previous works presented in
      the literature should be rediscussed on the basis of the new data.
      Photoelectrochemical mineralization of substrate in NaCl solution at the
      concentration of 16 mmol L-1 is comparable with the efficiency of the reaction in
      NaClO4 solution containing more than 8 mmol L-1 of NaClO. Total SCS
      mineralization was obtained in the photoelectrochemical reactor with a UV
      immersion lamp with a power 15 W in the period of 135 min and current intensity
      of 350 mA. In such conditions, the power consumption was about 1.2 kWh per g of
      TOC removed.

PMID- 24078756
TI  - Application of Reclaimed Wastewater in the Irrigation of Rosebushes.
AB  - The use of reclaimed wastewater in agriculture can be a solution for regions with
      water shortages or low rainfall periods; besides fulfilling the crop's water
      needs, it would also promote the recycle of nutrients. However, care should be
      taken regarding soil salinization, especially in closed environments such as
      greenhouses for the cultivation of ornamental plants. The domestic effluents are
      rich in sodium which can accumulate on soil and cause soil sealing. This study
      evaluated the use of effluents from anaerobic filters and intermittent sand
      filters in the production of rosebushes (Rosa hybrida "Ambiance"). The crop yield
      of the rosebushes irrigated with reclaimed wastewater exceeded the one obtained
      with traditional cultivation, reaching a value 31.8 % higher when employing
      nitrified effluent originated from intermittent sand filters, with no difference
      in the product quality. The salinity levels are below the critical limits found
      in the literature; however, there was a significant increase compared to the
      irrigation with drinking water.

PMID- 24078757
TI  - Bioaugmentation with Petroleum-Degrading Consortia Has a Selective Growth
      Promoting Impact on Crop Plants Germinated in Diesel Oil-Contaminated Soil.
AB  - Rhizoremediation is a complex type of green clean-up technology that involves
      both plants and the rhizosphere-associated microorganisms to decompose hazardous
      compounds. The success of the strategy strongly depends on plant tolerance
      towards the pollutant, as well as plant's interactions with the rhizospheric
      microbes. The microorganisms may be stimulated by the secreted root exudates,
      which results in an increased breakdown of contaminants in the rhizosphere. The
      main goal of this study was to establish a potential rhizoremediation combination
      for a diesel-polluted site. Inoculation of plant roots or seeds with indigenous
      rhizospheric populations is a common approach in the rhizoremediation. However,
      we introduced hydrocarbon-degrading consortia (M10, R3, and K52) that were
      previously isolated from crude oil-contaminated soil instead of indigenous
      microbes. Bioaugmentation with these petroleum degraders was applied to screen
      four high biomass crop species (Indian mustard, alfalfa, high erucic acid
      rapeseed, HEAR, and low erucic acid rapeseed, LEAR) for their tolerance towards
      diesel oil. At no pollution, a promoting effect of M10 bacteria could be observed
      on germination and root elongation of all plant species. Moreover, M10
      consortiums increased the germination index at 6,000 mg diesel oil per kilogram
      dry soil in the case of Indian mustard, alfalfa, and HEAR. The latter species was
      found to increment its dry weight upon bioaugmentation with M10 bacteria and all
      diesel oil treatments (6,000 and 24,000 mg diesel oil per kilogram dry soil). The
      initial results indicate HEAR and the M10 bacterial consortium as a promising
      plant-microbe tandem for a long-term rhizoremediation process.

PMID- 24078758
TI  - Poor working memory and reduced blood pressure levels in concurrent users of khat
      and tobacco.
AB  - INTRODUCTION: The purpose of this study was to examine the extent in which
      concurrent use of khat and tobacco was associated with decrements in working
      memory. We also tested whether cardiovascular activity during a cognitive task
      was related to performance outcomes, as research has shown linkages between
      maladaptive physiological adjustments and cognitive functions. METHODS: Seventy
      four concurrent users of khat and tobacco, 49 khat-only users, and 52 nonusers (M
      age +/- SD: 23.8+/-4.8) completed a laboratory session including 10 min of a
      mental arithmetic challenge task. Systolic blood pressure (SBP) and diastolic
      blood pressure and heart rate were collected throughout the task. Analyses of
      variance and correlational analyses were conducted. RESULTS: We found that
      concurrent users evidenced the lowest number of correct responses on the math
      task among these 3 groups (ps < .05). Concurrent users also showed fewer number
      of attempts than khat-only users (ps < .01) and lower accuracy rate than nonusers
      (ps < .05). The performance of khat-only users and nonusers were comparable on
      these 3 measures (p > .76). Overall blood pressure levels were lower in
      concurrent users than in nonusers (p < .05). Correlational analysis found that
      lower SBP during the math task was associated with fewer number of correct
      responses and attempts and lower accuracy rate on the task (ps < .05). Multiple
      regression analysis controlling for gender found that concurrent use predicted
      math performance (ps < .05). Reported duration and frequency of khat and tobacco
      use and nicotine dependence predicted performance measures (ps < .05).
      CONCLUSIONS: These findings suggest potential linkages between concurrent use of
      khat and tobacco and impaired working memory.

PMID- 24078759
TI  - Smoking motivation in adults with attention-deficit/hyperactivity disorder using
      the Wisconsin inventory of smoking dependence motives.
AB  - INTRODUCTION: Smokers with attention-deficit/hyperactivity disorder (ADHD) differ
      from smokers without ADHD across a range of smoking outcomes (e.g., higher
      prevalence rates of smoking, faster progression to regular smoking, and greater
      difficulty quitting). Moreover, ADHD as a disorder has been characterized by
      deficits in fundamental motivational processes. To date, few studies have
      examined how motivation for smoking might differ between nicotine-dependent
      individuals with and without ADHD. The goal of this study was to assess whether
      specific smoking motivation factors differentiate smokers with and without ADHD
      as measured by an empirically derived self-report measure of smoking motivations.
      METHODS: Smokers with (n = 61) and without (n = 89) ADHD participated in a range
      of laboratory and clinical studies that included the Wisconsin Inventory of
      Smoking Dependence Motives (WISDM). RESULTS: A series of one-way analysis of
      covariances statistically controlling for age and race indicated that smokers
      with ADHD scored higher on the following WISDM subscales than their non-ADHD
      peers: automaticity, loss of control, cognitive enhancement, cue exposure, and
      negative reinforcement. Smokers in the non-ADHD group yielded higher scores on
      the social- environmental goads WISDM subscale. No group by gender interactions
      emerged. CONCLUSIONS: Cigarette smokers with ADHD report different motives for
      smoking than smokers without ADHD. Clarifying the role of these motivational
      factors has implications for smoking prevention and treatment.

PMID- 24078761
TI  - Estimating Net Interracial Mobility in the U.S. A Residual Methods Approach.
AB  - This paper presents a residual methods approach to identifying social mobility
      across race/ethnic categories. In traditional demographic accounting models,
      population growth is limited to changes in natural increase and migration. Other
      sources of growth are absorbed by the model residual and can only be estimated
      indirectly. While these residual estimates have been used to illuminate a number
      of elusive demographic processes, there has been little effort to incorporate
      shifts in racial identification into formal accounts of population change. In
      light of growing evidence that a number of Americans view race/ethnic identities
      as a personal choice, and not a fixed characteristic, mobility across racial
      categories may play important roles in the growth of race/ethnic sub-populations
      and changes to the composition of the U.S. To examine this potential, we derive a
      reduced-form population balancing equation that treats fertility and
      international migration as given and estimates survival from period life table
      data. After subtracting out national increase and migration and adjusting the
      balance of observed growth for changes in racial measurement and census coverage,
      we argue that the remaining error of closure provides a reasonable estimate of
      net interracial mobility among the native born. Using recent Census and ACS
      microdata, we illustrate the impact that identity shifts may have had on the
      growth of race/ethnic sub-populations in the past quarter century. Findings
      suggest a small drift from the non-Hispanic white population into race/ethnic
      minority groups, though the pattern varies by age and between time periods.

PMID- 24078760
TI  - Decline in cue-provoked craving during cue exposure therapy for smoking
      cessation.
AB  - INTRODUCTION: Based on the principles of Pavlovian learning and extinction, cue
      exposure therapy (CET) involves repeated exposure to substance-associated cues to
      extinguish conditioned cravings and reduce the likelihood of relapse. The
      efficacy of CET is predicated on successful extinction, yet the process of
      extinction in CET trials has rarely been demonstrated. This study explored the
      extinction process using a cue-reactivity paradigm in smokers undergoing multiple
      CET sessions as part of a comprehensive smoking cessation treatment. METHODS: The
      sample comprised 76 moderately dependent, treatment-seeking smokers who completed
      at least 4 CET sessions and 6 counseling sessions. The CET and counseling
      sessions were scheduled twice weekly, and participants began using transdermal
      nicotine replacement therapy on their quit day, which occurred prior to
      initiation of CET. Each CET session consisted of presentation of 140 images on a
      computer screen, with self-reported craving as the primary measure of cue
      reactivity. RESULTS: Mixed-model analyses revealed a progressive decline in cue
      provoked craving both within and across 6 sessions of CET. Moderator analyses
      showed that the decline in craving was greatest among those who displayed initial
      cue reactivity. CONCLUSIONS: These data are consistent with the premise that CET
      can produce extinction of laboratory-based cue-provoked smoking cravings and
      highlight important individual differences that may influence extinction.
      Implications for conducting cue exposure research and interventions are
      discussed.

PMID- 24078762
TI  - Estimating the Proportion of True Null Hypotheses Using the Pattern of Observed p
      values.
AB  - Estimating the proportion of true null hypotheses, pi0, has attracted much
      attention in the recent statistical literature. Besides its apparent relevance
      for a set of specific scientific hypotheses, an accurate estimate of this
      parameter is key for many multiple testing procedures. Most existing methods for
      estimating pi0 in the literature are motivated from the independence assumption
      of test statistics, which is often not true in reality. Simulations indicate that
      most existing estimators in the presence of the dependence among test statistics
      can be poor, mainly due to the increase of variation in these estimators. In this
      paper, we propose several data-driven methods for estimating pi0 by incorporating
      the distribution pattern of the observed p-values as a practical approach to
      address potential dependence among test statistics. Specifically, we use a linear
      fit to give a data-driven estimate for the proportion of true-null p-values in
      (lambda, 1] over the whole range [0, 1] instead of using the expected proportion
      at 1 - lambda. We find that the proposed estimators may substantially decrease
      the variance of the estimated true null proportion and thus improve the overall
      performance.

PMID- 24078763
TI  - Strategies for Recruitment and Retention of Families from Low-Income, Ethnic
      Minority Backgrounds in a Longitudinal Study of Caregiver Feeding and Child
      Weight.
AB  - BACKGROUND: Children from low-SES and ethnic minority backgrounds are at
      heightened risk for overweight, yet are underrepresented in the pediatric obesity
      literature. METHODS: The current paper describes strategies employed to minimize
      barriers to recruitment and retention of African-American families receiving WIC
      services in a longitudinal study examining caregiver feeding and child weight.
      RESULTS: Seventy-six families enrolled in the study over 3.5 years, and 50% of
      the families completed the study. IMPLICATIONS FOR PRACTICE: Despite effortful
      planning, unanticipated barriers likely contributed to lengthy recruitment and a
      modest retention rate. Future research should incorporate lessons learned to
      modify and develop effective strategies for increasing engagement of low-SES and
      ethnic minority families in research.

PMID- 24078764
TI  - A COMPARISON OF POWER APPROXIMATIONS FOR SATTERTHWAITE'S TEST.
AB  - When testing equality of means from two independent normal populations, many
      statisticians prefer heterogeneity tolerant tests. Moser, Stevens, and Watts
      described the noncentral density and a numerical integration algorithm for
      computing power. We present simple and accurate approximations for the power of
      the Satterthwaite test statistic. Two advantages accrue. First, the
      approximations substantially reduce the computational burden for tasks such as
      plotting power curves. Second, the approximations substantially simplify the
      programming and thereby make power calculations more widely available. Four
      methods of power approximation are evaluated for test sizes of .001, .01, .05,
      and .10, sample sizes of 6 and 51, variance ratios of 1 and 10, and noncentrality
      parameters from 0 to 50 by 1. A method based on a ratio of expected values is
      recommended due to its accuracy and simplicity.

PMID- 24078765
TI  - Clinical Application of the P1 Cortical Auditory Evoked Potential Biomarker in
      Children with Sensorineural Hearing Loss and Auditory Neuropathy Spectrum
      Disorder.
AB  - The P1 component of the cortical auditory evoked potential (CAEP) shows clearly
      documented age-related decreases in latency and changes in morphology in normal
      hearing children, providing a biomarker for development of the auditory cortical
      pathways in humans. In hearing-impaired children, auditory deprivation may affect
      the normal age-related changes in central auditory maturation. Appropriate early
      intervention with amplification and/or electrical stimulation can provide the
      necessary stimulation needed to drive progress in central auditory maturation and
      auditory skill development, however objective measures are needed to evaluate the
      effectiveness of these treatments in infants and young children. We describe
      three pediatric cases, where we explored the clinical utility of the P1 as an
      objective biomarker of auditory cortical development after early intervention. We
      assessed development of P1 CAEP latency and morphology in two children with
      sensorineural hearing loss (SNHL) who received intervention with hearing aids
      (case 1) and cochlear implants (case 2) and a child with Auditory Neuropathy
      Spectrum Disorder (ANSD) (case 3). Overall, we find that the P1 CAEP serves as
      useful tool for assessing the effectiveness of early intervention treatment and
      clinical management of pediatric hearing- impaired patients.

PMID- 24078766
TI  - Integrating transient heterogeneity of non-photochemical quenching in shade-grown
      heterobaric leaves of avocado (Persea americana L.): responses to CO2
      concentration, stomatal occlusion, dehydration and relative humidity.
AB  - Long-lived shade leaves of avocado had extremely low rates of photosynthesis. Gas
      exchange measurements of photosynthesis were of limited use, so we resorted to
      Chl fluorescence imaging (CFI) and spot measurements to evaluate photosynthetic
      electron transport rates (ETRs) and non-photochemical quenching (NPQ). Imaging
      revealed a remarkable transient heterogeneity of NPQ during photosynthetic
      induction in these hypostomatous, heterobaric leaves, but was adequately
      integrated by spot measurements, despite long-lasting artifacts from repeated
      saturating flashes during assays. Major veins (mid-vein, first- and second-order
      veins) defined areas of more static large-scale heterogeneous NPQ, with more
      dynamic small-scale heterogeneity most strongly expressed in mesophyll cells
      between third- and fourth-order veins. Both responded to external CO2
      concentration ([CO2]), occlusion of stomata with VaselineTM, leaf dehydration and
      relative humidity (RH). We interpreted these responses in terms of independent
      behavior of stomata in adjacent areoles that was largely expressed through CO2
      limited photosynthesis. Heterogeneity was most pronounced and prolonged in the
      absence of net CO2 fixation in 100 p.p.m. [CO2] when respiratory and
      photorespiratory CO2 cycling constrained the inferred ETR to ~75% of values in
      400 or 700 p.p.m. [CO2]. Likewise, sustained higher NPQ under VaselineTM, after
      dehydration or at low RH, also restricted ETR to ~75% of control values. Low NPQ
      in chloroplast-containing cells adjacent to major veins but remote from stomata
      suggested internal sources of high [CO2] in these tissues.

PMID- 24078767
TI  - HISN3 mediates adaptive response of Chlamydomonas reinhardtii to excess nickel.
AB  - Investigation of genes for heavy metal [e.g. nickel (Ni) and zinc (Zn)]
      absorption and detoxification in green algae is of great importance because some
      of the metals have become one of the major contaminants in the aquatic ecosystem.
      In plants, overload of heavy metals modifies many aspects of biological
      processes. However, the mechanisms by which heavy metals exert detrimental
      effects are not fully understood. The present study identified a biological role
      for HISN3 (the gene coding for phosphoribosylformimino-5-aminoimidazole
      carboxamide ribonucleotide isomerase) in regulating the response of Chlamydomonas
      reinhardtii, a unicellular green alga, to Ni toxicity. In higher plants, HISN3
      encodes an enzyme catalyzing the fourth step in the histidine biosynthesis
      pathway, but its functional importance is yet to be identified. Transgenic algae
      overexpressing HISN3 in C. reinhardtii showed high tolerance to excess Ni, with a
      48.3-57.4% increase in cell population and moderate histidine accumulation
      compared with the wild type. HISN3 overexpression improved accumulation of Chl
      and photosynthesis efficiency, but suppressed Ni-induced generation of reactive
      oxygen species and lipid peroxides. Interestingly, more Ni and other metals [Zn,
      iron (Fe), copper (Cu), manganese (Mn) and magnesium (Mg)] were accumulated in
      HISN3-overexpressing cells than in the wild type. In contrast, RNA interference
      of HISN3 depressed Ni accumulation but caused cellular sensitivity to Ni. The
      elevated metal absorption in the HISN3-overexpressing algae implies that the
      metals can be removed from water media. Thus, our work presents an example for
      algae genetically designed to improve tolerance to metal toxicity and
      environmental restoration of metal-contaminated aquatic ecosystems.

PMID- 24078768
TI  - Tunable drug release profiles from salicylate-based poly(anhydride-ester)
      matrices using small molecule admixtures.
AB  - Poly(anhydride-esters) with salicylic acid, a nonsteroidal anti-inflammatory
      drug, chemically incorporated into the polymer backbone provide high inherent
      drug loading. These poly(anhydride-esters) hydrolytically degrade to release
      salicylic acid over extended time periods (>30 days); however, an initial lag
      period of no salicylic acid release is observed. This lag period could be
      unfavorable in applications where immediate salicylic acid release is desired.
      Poly(anhydride-esters) with short (2 days) and long (11 days) lag periods were
      admixed with various small molecules as a means to shorten or eliminate the lag
      period. Salicylic acid, larger salicylic acid prodrugs, and 1:1 combinations of
      the two were physically admixed, each at 1%, 5%, and 10% (w/w). All admixtures
      resulted in immediate salicylic acid release and a decrease in glass transition
      temperatures compared to polymer alone. By varying the amounts of salicylic acid
      and salicylic acid prodrugs incorporated into the polymer matrix, immediate and
      constant salicylic acid release profiles over varied time periods were achieved.

PMID- 24078769
TI  - Trauma Systems Therapy in Residential Settings: Improving Emotion Regulation and
      the Social Environment of Traumatized Children and Youth in Congregate Care.
AB  - Although abundant evidence exists indicating the prevalence of trauma exposure
      among youth in residential care, few models exist for creating trauma-informed
      milieu treatment. This article outlines the problem and describes the
      implementation of Trauma Systems Therapy (TST) in three residential centers. TST
      is unique in emphasizing youth emotions and behaviors as well as the role a
      distressed or threatening social environment may play in keeping a traumatized
      youth in a dysregulated state. This dual emphasis makes TST specifically
      appropriate to implementation in congregate care, focusing assessment and
      intervention strategies on both clinical treatment and the functioning of the
      therapeutic milieu itself. Data are reported on incidents of the use of physical
      restraint; numbers of disrupted foster care placements following discharge from
      residential treatment; and scores on psychometric measures of children's
      functioning and emotion regulation capacity. Knowledge gained through TST
      implementation in these three residential centers has important implications for
      developing a model of trauma-informed congregate care.

PMID- 24078770
TI  - Improving treatment adherence in patients with rheumatologic disease.
AB  - Further evaluation of reasons for treatment nonadherence in patients with
      rheumatologic disease is key in the development of successful interventions.
      Patient education efforts alone are not sufficient to improve adherence; complex
      interventions are most effective. Because most rheumatologic diseases require
      lifetime therapy, the consequences of nonadherence can be deleterious. Several
      direct and indirect methods have been proposed to measure adherence. Pharmacy
      claims data have been used frequently in studying rheumatologic disease;
      electronic monitoring provides an accurate measure. Adherence is mediated through
      constructs of the patient-physician relationship.

PMID- 24078771
TI  - Meeting report - oocyte maturation and fertilization: lessons from canonical and
      emerging models.
AB  - The EMBO workshop 'Oocyte maturation and fertilization: lessons from canonical
      and emerging models' was held at the Oceanologic Observatory of Banyuls in France
      in June 2013 and was organized by Anne-Marie Geneviere, Olivier Haccard, Peter
      Lenart and Alex McDougall. A total of 78 participants shared their research on
      germline formation, oocyte development, sperm, fertilization and early
      development. Here, we report the highlights of this meeting. 

PMID- 24078772
TI  - A fluorescent colorimetric pH sensor and the influences of matrices on sensing
      performances.
AB  - A fluorescent colorimetric pH sensor was developed by a polymerization of a
      monomeric fluorescein based green emitter (SM1) with a monomeric 2
      dicyanomethylene-3-cyano-4,5,5-trimethyl-2,5-dihydrofuran derived red emitter
      (SM2) in poly(2-hydroxyethyl methacrylate)-co-polyacrylamide (PHEMA-co-PAM)
      matrices. Polymerized SM1 (PSM1) in the polymer matrices showed bright emissions
      at basic conditions and weak emissions at acidic conditions. Polymerized SM2
      (PSM2) in the polymer matrices exhibited a vastly different response when
      compared to PSM1. The emissions of PSM2 are stronger under acidic conditions than
      those under basic conditions. When SM1 and SM2 were polymerized in the same
      polymer matrix, a dual emission sensor acting as a ratiometric pH sensor (PSM1,2)
      was successfully developed. Because the PSM1 and PSM2 exhibited different pH
      responses and separated emission windows, the changes in the emission colors were
      clearly observed in their dual color sensor of PSM1,2, which changed emission
      colors dramatically from green at pH 7 to red at pH 4, which was detected
      visually and/or by using a color camera under an excitation of 488 nm. In
      addition to the development of the dual color ratiometric pH sensor, we also
      studied the effects of different matrix compositions, crosslinkers, and charges
      on the reporting capabilities of the sensors (sensitivity and pKa).

PMID- 24078773
TI  - A drug repositioning approach identifies tricyclic antidepressants as inhibitors
      of small cell lung cancer and other neuroendocrine tumors.
AB  - Small cell lung cancer (SCLC) is an aggressive neuroendocrine subtype of lung
      cancer with high mortality. We used a systematic drug repositioning
      bioinformatics approach querying a large compendium of gene expression profiles
      to identify candidate U.S. Food and Drug Administration (FDA)-approved drugs to
      treat SCLC. We found that tricyclic antidepressants and related molecules
      potently induce apoptosis in both chemonaive and chemoresistant SCLC cells in
      culture, in mouse and human SCLC tumors transplanted into immunocompromised mice,
      and in endogenous tumors from a mouse model for human SCLC. The candidate drugs
      activate stress pathways and induce cell death in SCLC cells, at least in part by
      disrupting autocrine survival signals involving neurotransmitters and their G
      protein-coupled receptors. The candidate drugs inhibit the growth of other
      neuroendocrine tumors, including pancreatic neuroendocrine tumors and Merkel cell
      carcinoma. These experiments identify novel targeted strategies that can be
      rapidly evaluated in patients with neuroendocrine tumors through the repurposing
      of approved drugs. SIGNIFICANCE: Our work shows the power of bioinformatics-based
      drug approaches to rapidly repurpose FDA-approved drugs and identifies a novel
      class of molecules to treat patients with SCLC, a cancer for which no effective
      novel systemic treatments have been identified in several decades. In addition,
      our experiments highlight the importance of novel autocrine mechanisms in
      promoting the growth of neuroendocrine tumor cells.

PMID- 24078774
TI  - Activation of the PD-1 pathway contributes to immune escape in EGFR-driven lung
      tumors.
AB  - The success in lung cancer therapy with programmed death (PD)-1 blockade suggests
      that immune escape mechanisms contribute to lung tumor pathogenesis. We
      identified a correlation between EGF receptor (EGFR) pathway activation and a
      signature of immunosuppression manifested by upregulation of PD-1, PD-L1, CTL
      antigen-4 (CTLA-4), and multiple tumor-promoting inflammatory cytokines. We
      observed decreased CTLs and increased markers of T-cell exhaustion in mouse
      models of EGFR-driven lung cancer. PD-1 antibody blockade improved the survival
      of mice with EGFR-driven adenocarcinomas by enhancing effector T-cell function
      and lowering the levels of tumor-promoting cytokines. Expression of mutant EGFR
      in bronchial epithelial cells induced PD-L1, and PD-L1 expression was reduced by
      EGFR inhibitors in non-small cell lung cancer cell lines with activated EGFR.
      These data suggest that oncogenic EGFR signaling remodels the tumor
      microenvironment to trigger immune escape and mechanistically link treatment
      response to PD-1 inhibition. SIGNIFICANCE: We show that autochthonous EGFR-driven
      lung tumors inhibit antitumor immunity by activating the PD-1/PD-L1 pathway to
      suppress T-cell function and increase levels of proinflammatory cytokines. These
      findings indicate that EGFR functions as an oncogene through non-cell-autonomous
      mechanisms and raise the possibility that other oncogenes may drive immune
      escape.

PMID- 24078775
TI  - Palmitic acid induces production of proinflammatory cytokines interleukin-6,
      interleukin-1beta, and tumor necrosis factor-alpha via a NF-kappaB-dependent
      mechanism in HaCaT keratinocytes.
AB  - To investigate whether palmitic acid can be responsible for the induction of
      inflammatory processes, HaCaT keratinocytes were treated with palmitic acid at
      pathophysiologically relevant concentrations. Secretion levels of interleukin-6
      (IL-6), tumor necrosis factor- alpha (TNF- alpha), interleukin-1 beta (IL-1
      beta), NF- kappa B nuclear translocation, NF- kappa B activation, Stat3
      phosphorylation, and peroxisome proliferator-activated receptor alpha (PPAR
      alpha) mRNA and protein levels, as well as the cell proliferation ability were
      measured at the end of the treatment and after 24 hours of recovery. Pyrrolidine
      dithiocarbamate (PDTC, a selective chemical inhibitor of NF- kappa B) and goat
      anti-human IL-6 polyclonal neutralizing antibody were used to inhibit NF- kappa B
      activation and IL-6 production, respectively. Our results showed that palmitic
      acid induced an upregulation of IL-6, TNF- alpha , IL-1 beta secretions,
      accompanied by NF- kappa B nuclear translocation and activation. Moreover, the
      effect of palmitic acid was accompanied by PPAR alpha activation and Stat3
      phosphorylation. Palmitic acid-induced IL-6, TNF- alpha , IL-1 beta productions
      were attenuated by NF- kappa B inhibitor PDTC. Palmitic acid was administered in
      amounts able to elicit significant hyperproliferation and can be attenuated by IL
      6 blockage. These data demonstrate for the first time that palmitic acid can
      stimulate IL-6, TNF- alpha , IL-1 beta productions in HaCaT keratinocytes and
      cell proliferation, thereby potentially contributing to acne inflammation and
      pilosebaceous duct hyperkeratinization.

PMID- 24078776
TI  - SOCS3 expression correlates with severity of inflammation, expression of
      proinflammatory cytokines, and activation of STAT3 and p38 MAPK in LPS-induced
      inflammation in vivo.
AB  - SOCS3 is an inducible endogenous negative regulator of JAK/STAT pathway, which is
      relevant in inflammatory conditions. We used a model of LPS-induced periodontal
      disease in rats to correlate SOCS3 expression with the inflammatory status. In
      vitro we used a murine macrophage cell line to assess the physical interaction
      between SOCS3 and STAT3 by coimmunoprecipitation. 30 ug of LPS from Escherichia
      coli were injected in the gingival tissues on the palatal aspect of first molars
      of the animals 3x/week for up to 4 weeks. Control animals were injected with the
      vehicle (PBS). The rats were sacrificed at 7, 15, and 30 days. Inflammation and
      gene expression were assessed by stereometric analysis, immunohistochemistry, RT
      qPCR, and western blot. LPS injections increased inflammation, paralleled by an
      upregulation of SOCS3, of the proinflammatory cytokines IL-1 beta , IL-6, and TNF
      alpha and increased phosphorylation of STAT3 and p38 MAPK. SOCS3 expression
      accompanied the severity of inflammation and the expression of proinflammatory
      cytokines, as well as the activation status of STAT3 and p38 MAPK. LPS
      stimulation in a macrophage cell line in vitro induced transient STAT3
      activation, which was inversely correlated with a dynamic physical interaction
      with SOCS3, suggesting that this may be a mechanism for SOCS3 regulatory
      function.

PMID- 24078777
TI  - Increased serum ox-LDL levels correlated with lung function, inflammation, and
      oxidative stress in COPD.
AB  - Chronic obstructive pulmonary disease (COPD) is associated with abnormal
      inflammation and high oxidative stress. Studies suggest that oxidized low density
      lipoprotein (ox-LDL) is involved in diseases associated with oxidative stress and
      inflammation. However, no data on the possible relationship between COPD and ox
      LDL are available. This study compared serum levels of ox-LDL in 48 COPD patients
      and 32 health controls and correlated them with lung function, systematic
      inflammation, and oxidative stress. Serum levels of ox-LDL, C-reactive protein
      (CRP), and oxidative stress (measured by reactive oxygen species, ROS) were
      analyzed using commercial kits. Mean levels of serum ox-LDL were significantly
      higher in COPD patients than in controls (18.62 +/- 7.56 versus 12.57 +/- 5.90
      mU/L, P < 0.05). Serum levels of CRP and ROS were also significantly higher in
      COPD patients. Serum levels of ox-LDL in COPD patients correlated inversely with
      FEV1% predicted, an index of lung function (r = -0.347, P = 0.016), while they
      correlated positively with CRP and ROS levels. These results suggest that serum
      levels of ox-LDL are increased in COPD patients and that these levels are
      associated with lung function, inflammation, and oxidative stress in COPD. Future
      studies are needed to determine whether and how ox-LDL plays a role in COPD.

PMID- 24078778
TI  - Victimization and Violent Offending: An Assessment of the Victim-Offender Overlap
      Among Native American Adolescents and Young Adults.
AB  - The purpose of this article is to evaluate the victim-offender overlap among a
      nationally representative sample of Native American adolescents and young adults.
      Data for this study were obtained from 338 Native American youth who participated
      in the National Longitudinal Study of Adolescent Health (Add Health) Waves I-IV.
      Group-based trajectory modeling was used to estimate trajectories of violence and
      victimization separately. Bivariate tests were used to assess the overlap between
      victimization and violent trajectory groups. Multinomial regression procedures
      were used to assess the predictors of victimization, offending, and the overlap
      category of both victimization and offending. Three trajectory groups were found
      for violence (nonviolent, escalators, and desistors) and victimization
      (nonvictim, decreasing victimization, and increasing victimization). We found
      substantial evidence of an overlap between victimization and offending among
      Native Americans, as 27.5% of the sample reported both victimization and
      offending. Those in the overlap group had greater number of risk factors present
      at baseline. These results suggest that the victim-offender overlap is present in
      Native American adolescents. Explanations and implications are discussed.

PMID- 24078779
TI  - Clinical and ethical aspects of financial capacity in dementia: a commentary.
AB  - In contrast to issues like treatment and research consent capacity, financial
      capacity has received relatively little clinical and ethical attention in the
      dementia literature. Yet issues of financial capacity emerge frequently in
      patients with Alzheimer's disease (AD), Parkinson's disease (PD) and related
      dementias, and commonly present ethical and clinical challenges for clinicians
      treating these patients. These issues include whether a patient with possible
      dementia has sufficient capacity independently to manage their financial affairs,
      needs referral for financial capacity assessment, and/or is being financially
      exploited or abused by others. The accurate identification, assessment and
      successful handling of such financial capacity issues can have a substantial
      impact on the financial and psychological well-being of patients and their family
      members. The present commentary presents an overview of financial capacity and
      associated clinical and ethical issues in dementia, and describes a set of
      possible clinician roles regarding these issues as they arise in clinical
      practice. The commentary concludes with a section describing educational
      resources available to clinicians and bioethicists seeking additional guidance in
      handling financial capacity issues. The ultimate goal of the paper is to focus
      clinical and ethical attention on a neglected capacity that is of fundamental
      importance for patients, families, and health care and legal professionals. 

PMID- 24078780
TI  - Endorsement of a Personal Responsibility to Adhere to the Minimum Drinking Age
      Law Predicts Consumption, Risky Behaviors, and Alcohol-Related Harms.
AB  - Despite minimum drinking age laws, underage college students engage in high
      levels of risky drinking and reach peak lifetime levels of alcohol dependence. A
      group of presidents of universities and colleges has argued that these laws
      promote disrespect for laws in general, and do not prevent drinking or related
      negative consequences. However, no study has investigated the policy-relevant
      question of whether students who endorse a personal responsibility to obey
      drinking laws, regardless of their opinions about the laws, are less likely to
      drink or to experience negative consequences. Therefore, we compared endorsers to
      non-endorsers, controlling for race, gender, and baseline outcomes, at two
      universities (Ns = 2007 and 2027). Neither sample yielded a majority (49% and 38%
      endorsement), but for both universities, all 17 outcome measures were
      significantly associated with endorsement across all types of analyses. Endorsers
      were less likely to drink, drank less, engaged in less high-risk behavior (e.g.,
      heavy/binge drinking), and experienced fewer harms (e.g., physical injury), even
      when controlling for covariates. Racial/ethnic minority groups were more likely
      to endorse, compared to White students. By isolating a small window of time
      between high school and college that produces large changes in drinking behavior,
      and controlling for covariates, we can begin to hone in on factors that might
      explain relations among laws, risky behaviors, and harms. Internalization of a
      social norm to adhere to drinking laws could offer benefits to students and
      society, but subsequent research is needed to pin down causation and causal
      mechanisms.

PMID- 24078781
TI  - Perceptions of health and risk management among home care workers in Sweden.
AB  - BACKGROUND: Municipal home care workers provide high-quality services to an
      increasing proportion of elderly people living in private homes. The work
      environments and working conditions of these workers vary to a great extent,
      implying rapid priority-making among both employers and employees to ensure that
      the work can be performed in a safe way. OBJECTIVES: This study aims to examine
      home care workers' perceptions of health, risks, working conditions, and risk
      management within their organization. METHOD: The study was based on cross
      sectional data collected from home care service staff in a municipality in the
      north of Sweden. Nursing assistants and care aides (n = 133) replied to a self
      administered questionnaire. Descriptive statistics and between-group differences
      were analysed. RESULTS: Home care work was perceived to require high levels of
      professional skill and ingenuity, a good psychosocial work situation, but
      required a high physical workload. The general health, the capacity and self
      efficacy of the staff in relation to work were good. Difficulty in performing
      risk assessments and following safety regulations due to lack of time, equipment,
      and information were identified. CONCLUSION: There is a need to increase
      participation in risk assessments among the staff, improve management support,
      structures, and cooperation with other divisions of the social services and the
      medical care organizations.

PMID- 24078782
TI  - Impact of COMT Val158Met on executive functioning in the context of HIV and
      methamphetamine.
AB  - The catechol-O-methyltransferease (COMT) Val allele has been linked to executive
      dysfunction among healthy individuals. The nature of this relationship is unknown
      in the context of HIV infection and/or methamphetamine (METH) dependence, two
      conditions that can alter dopaminergic system functioning. We sought to determine
      if the putative relationship between COMT and executive dysfunction could be
      observed among individuals with and without HIV-infection and/or METH dependence,
      and to explore the specificity of this relationship by examining other cognitive
      domains. Utilizing an existing cohort of 229 men with and without HIV infection
      and/or METH dependence we found that Met/Met carriers within the HIV-only and
      control groups, displayed better executive functioning compared to Val/Val and
      Val/Met carriers. However, this effect was attenuated in the METH-only and
      comorbid (ie, HIV+/METH+) groups. Examination of other neurocognitive domains
      were not consistent with effects found for executive functioning. Results support
      the presumed neuroprotective effect of Met/Met genotype on executive functioning
      among HIV-only and control groups. Among METH-only and comorbid groups, the
      slower rate of dopamine clearance conferred by the Met/Met genotype may increase
      the risk of adverse effects of METH, resulting in comparable executive
      dysfunction to that of Val allele carriers.

PMID- 24078783
TI  - Prenatal-postnatal correlations of brain abnormalities: how lesions and diagnoses
      change over time.
AB  - A combination of prenatal ultrasound and MRI can be used to detect and
      characterize many primary and secondary CNS abnormalities in the developing
      fetus. While this information is useful in prenatal patient counseling, it is
      important to understand the factors that can influence change in diagnosis and
      prognosis over time. The etiology of the abnormality, the conspicuity of
      associated findings, the change in appearance over time, and the opinion of
      subspecialty experts all can influence the diagnosis. Additionally, technical
      factors of imaging acquisition may allow the detection of an abnormality in the
      postnatal period and not prenatally. Having an understanding of the normal fetal
      central nervous system anatomy at varying gestational ages will aid in the
      imaging detection and interpretation of CNS pathology. Understanding how these
      appearances and diagnoses can change over time will aid in the discussion of
      prognosis with expectant parents, which is crucial in fetal CNS abnormalities.

PMID- 24078784
TI  - Correlates of health-related quality of life in pediatric inflammatory bowel
      disease: a cumulative risk model approach.
AB  - OBJECTIVE: To examine associations between disease-related, individual, and
      contextual risk factors and health-related quality of life (HRQoL) in a sample of
      youth with inflammatory bowel disease using a cumulative risk model framework.
      METHODS: Participants were 50 youth (58% male; M age = 15 years). Youth and
      parents completed measures of HRQoL, psychological functioning, and family
      functioning. Disease information was collected from medical record reviews.
      Medication adherence was electronically monitored via MEMS cap bottles. A
      cumulative risk index (CRI) was constructed based on disease activity, disease
      type, gender, anxiety/depression, medication adherence, general family
      functioning, disease-specific family functioning, and socioeconomic status.
      RESULTS: The CRI was associated with all youth- and mother-reported HRQoL
      domains. Furthermore, contextual domain factors were most consistently associated
      with youth and maternal reports of HRQoL. CONCLUSION: These results show promise
      in supporting the value of the CRI in identifying potential risk factors for
      lower HRQoL in a cross-sectional sample.

PMID- 24078786
TI  - Molecular and phenotypic characterization of seedling and adult plant leaf rust
      resistance in a world wheat collection.
AB  - Genetic resistance is the most effective approach to managing wheat leaf rust.
      The aim of this study was to characterize seedling and adult plant leaf rust
      resistance of a world wheat collection. Using controlled inoculation with ten
      races of Puccinia triticina, 14 seedling resistance genes were determined or
      postulated to be present in the collection. Lr1, Lr3, Lr10 and Lr20 were the most
      prevalent genes around the world while Lr9, Lr14b, Lr3ka and/or Lr30 and Lr26
      were rare. To confirm some gene postulations, the collection was screened with
      gene-specific molecular markers for Lr1, Lr10, Lr21 and Lr34. Although possessing
      the Lr1 and/or Lr10 gene-specific marker, 51 accessions showed unexpected high
      infection types to P. triticina race BBBD. The collection was tested in the
      field, where rust resistance ranged from nearly immune or highly resistant with
      severity of 1 % and resistant host response to highly susceptible with severity
      of 84 % and susceptible host response. The majority of the accessions possessing
      the adult plant resistance (APR) gene Lr34 had a maximum rust severity of 0-35 %,
      similar to or better than accession RL6058, a Thatcher-Lr34 near-isogenic line.
      Many accessions displayed an immune response or a high level of resistance under
      field conditions, likely as a result of synergy between APR genes or between APR
      and seedling resistance genes. However, accessions with three or more seedling
      resistance genes had an overall lower field severity than those with two or
      fewer. Immune or highly resistant accessions are potential sources for
      improvement of leaf rust resistance. In addition, some lines were postulated to
      have known but unidentified genes/alleles or novel genes, also constituting
      potentially important sources of novel resistance.

PMID- 24078787
TI  - The uncertain representation ranking framework for concept-based video retrieval.
AB  - Concept based video retrieval often relies on imperfect and uncertain concept
      detectors. We propose a general ranking framework to define effective and robust
      ranking functions, through explicitly addressing detector uncertainty. It can
      cope with multiple concept-based representations per video segment and it allows
      the re-use of effective text retrieval functions which are defined on similar
      representations. The final ranking status value is a weighted combination of two
      components: the expected score of the possible scores, which represents the risk
      neutral choice, and the scores' standard deviation, which represents the risk or
      opportunity that the score for the actual representation is higher. The framework
      consistently improves the search performance in the shot retrieval task and the
      segment retrieval task over several baselines in five TRECVid collections and two
      collections which use simulated detectors of varying performance.

PMID- 24078785
TI  - Utilization of transposable element mPing as a novel genetic tool for
      modification of the stress response in rice.
AB  - Transposable elements (TEs) are DNA fragments that have the ability to move from
      one chromosomal location to another. The insertion of TEs into gene-rich regions
      often affects changes in the expression of neighboring genes. Miniature Ping
      (mPing) is an active miniature inverted-repeat TE discovered in the rice genome.
      It has been found to show exceptionally active transposition in a few japonica
      rice varieties, including Gimbozu, where mPing insertion rendered adjacent genes
      stress-inducible. In the Gimbozu population, it is highly possible that several
      genes with modified expression profiles are segregating due to the de novo mPing
      insertions. In our study, we utilized a screening system for detecting de novo
      mPing insertions in the upstream region of target genes and evaluated the effect
      of mPing on the stress response of the target genes. Screening for 17 targeted
      genes revealed five genes with the mPing insertion in their promoters. In most
      cases, the alteration of gene expression was observed under stress conditions,
      and there was no change in the expression levels of those five genes under normal
      conditions. These results indicate that the mPing insertion can be used as a
      genetic tool to modify an expression pattern of a target gene under stress
      conditions without changing the expression profiles of those under natural
      conditions.

PMID- 24078788
TI  - Combining field epidemiological information and genetic data to comprehensively
      reconstruct the invasion history and the microevolution of the sudden oak death
      agent Phytophthora ramorum (Stramenopila: Oomycetes) in California.
AB  - Understanding the migration patterns of invasive organisms is of paramount
      importance to predict and prevent their further spread. Previous attempts at
      reconstructing the entire history of the sudden oak death (SOD) epidemic in
      California were limited by: (1) incomplete sampling; (2) the inability to include
      infestations caused by a single genotype of the pathogen; (3) collapsing of non
      spatially contiguous yet genetically similar samples into large meta-samples that
      confounded the coalescent analyses. Here, we employ an intensive sampling
      coverage of 832 isolates of Phytopthora ramorum (the causative agent of SOD) from
      60 California forests, genotyped at nine microsatellite loci, to reconstruct its
      invasion. By using age of infestation as a constraint on coalescent analyses, by
      dividing genetically indistinguishable meta-populations into highly-resolved sets
      of spatially contiguous populations, and by using Bruvo genetic distances for
      most analyses, we reconstruct the entire history of the epidemic and convincingly
      show infected nursery plants are the original source for the entire California
      epidemic. Results indicate that multiple human-mediated introductions occurred in
      most counties and that further disease sources were represented by large wild
      infestations. The study also identifies minor introductions, some of them
      relatively recent, linked to infected ornamental plants. Finally, using archival
      isolates collected soon after the discovery of the pathogen in California, we
      corroborate that the epidemic is likely to have resulted form 3 to 4 core founder
      individuals evolved from a single genotype. This is probably the most complete
      reconstruction ever completed for an invasion by an exotic forest pathogen, and
      the approach here described may be useful for the reconstruction of invasions by
      any clonally reproducing organism with a relatively limited natural dispersal
      range.

PMID- 24078789
TI  - Effects of serum on cytotoxicity of nano- and micro-sized ZnO particles.
AB  - Although an increasing number of in vitro studies are being published regarding
      the cytotoxicity of nanomaterials, the components of the media for toxicity
      assays have often varied according to the needs of the scientists. Our aim for
      this study was to evaluate the influence of serum-in this case, fetal bovine
      serum-in a cell culture medium on the toxicity of nano-sized (50-70 nm) and micro
      sized (<1 MUm) ZnO on human lung epithelial cells (A549). The nano- and micro
      sized ZnO both exhibited their highest toxicity when exposed to serum-free media,
      in contrast to exposure in media containing 5 or 10 % serum. This mainly comes
      not only from the fact that ZnO particles in the serum-free media have a higher
      dosage-per-cell ratio, which results from large aggregates of particles, rapid
      sedimentation, absence of protein protection, and lower cell growth rate, but
      also that extracellular Zn2+ release contributes to cytotoxicity. Although more
      extracellular Zn2+ release was observed in serum-containing media, it did not
      contribute to nano-ZnO cytotoxicity. Furthermore, non-dissolved particles
      underwent size-dependent particle agglomeration, resulting in size-dependent
      toxicity in both serum-containing and serum-free media. A low correlation between
      cytotoxicity and inflammation endpoints in the serum-free medium suggested that
      some signaling pathways were changed or induced. Since cell growth, transcription
      behavior for protein production, and physicochemical properties of ZnO particles
      all were altered in serum-free media, we recommend the use of a serum-containing
      medium when evaluating the cytotoxicity of NPs.

PMID- 24078790
TI  - Water molecular flow control with a (5,5) nanocoil switch.
AB  - Molecular dynamics simulation was employed to investigate the diffusion behaviors
      of water molecules within a (5,5) carbon nanocoil (CNC) at different tensile
      strains, the length and coil diameter of CNC are 22 and 6.83 A, respectively.
      Condensed-phase, optimized molecular potentials for atomistic simulation studies
      were employed to model the interaction between atoms. The results show that the
      diffusion in the axial direction can be enhanced by the tensile strain and the
      water molecule flow can be blocked at a higher strain once the deformed areas
      appear at the higher strain. Moreover, the deformed (5,5) CNC at strain of 2.8
      can recover its original structure at strain of 0, indicating that the adjustment
      of diffusion coefficient is repeatable by applying different strains in the axial
      direction.

PMID- 24078791
TI  - Chitosan-capped gold nanoparticles for selective and colorimetric sensing of
      heparin.
AB  - In this contribution, novel chitosan-stabilized gold nanoparticles (AuNPs) were
      prepared by mixing chitosan with citrate-reductive AuNPs under appropriate
      conditions. The as-prepared chitosan-stabilized AuNPs were positively charged and
      highly stably dispersed in aqueous solution. They exhibited weak resonance light
      scattering (RLS) intensity and a wine red color. In addition, the chitosan
      stabilized AuNPs were successfully utilized as novel sensitive probes for the
      detection of heparin for the first time. It was found that the addition of
      heparin induced a strong increase of RLS intensity for AuNPs and the color change
      from red to blue. The increase in RLS intensity and the color change of chitosan
      stabilized AuNPs caused by heparin allowed the sensitive detection of heparin in
      the range of 0.2-60 MUM (~6.7 U/mL). The detection limit for heparin is 0.8 MUM
      at a signal-to-noise ratio of 3. The present sensor for heparin detection
      possessed a low detection limit and wide linear range. Additionally, the proposed
      method was also applied to the detection of heparin in biological media with
      satisfactory results.

PMID- 24078792
TI  - How Well Does the American Community Survey Count Naturalized Citizens?
AB  - BACKGROUND: Citizenship status among the foreign born is a crucial indicator of
      social and political incorporation, yet there are good reasons to suspect that
      citizenship status is inaccurately reported on U.S. surveys. OBJECTIVE: This
      paper updates research carried out in the mid-1990s by Passel and Clark (1997) on
      the extent to which foreign-born non-citizen respondents in U.S. government
      sponsored surveys misreport as naturalized citizens. METHODS: We compare
      demographic estimates of the resident naturalized foreign-born population in
      2010, based on administrative data, to estimates from the 2010 American Community
      Survey (ACS). RESULTS: Similar to previous research, we find that misreporting in
      the ACS is especially high among immigrants from all countries/regions who report
      fewer than five years in the U.S. We also find that among longer-term foreign
      born residents, misreporting is concentrated only among those originating in
      Mexico, especially men, a finding that diverges from Passel and Clark in that we
      find no evidence of over-reporting among immigrants from Central America and the
      Caribbean. Finally, the estimated magnitude of misreporting, especially among
      longer-term Mexican-born men, is sensitive to assumptions about the rate of
      emigration in our administrative-based demographic estimates, and assumptions
      about coverage error in the ACS, though altering these assumptions does not
      change the conclusions drawn from the general patterns of the results.
      CONCLUSIONS: For applications that use citizenship as an indicator of legal
      status, we recommend that self-reported data on citizenship be accepted at face
      value for all groups except those with less than five years of U.S. residence and
      Mexican men.

PMID- 24078793
TI  - A wireless hybrid chemical sensor for detection of environmental volatile organic
      compounds.
AB  - A hybrid sensor for monitoring volatile organic compounds (VOCs) in air is
      developed. The device combines two orthogonal sensing principles, selective
      molecular binding with a microfabricated quartz tuning fork detector and
      separation of analytes with a column. The tuning fork detector is functionalized
      with molecular imprinted polymers for selective binding to benzene, toluene,
      ethylbenzene, and xylenes (BTEX), and the separation column provides further
      discrimination of the analytes for real world complex sample analysis. The device
      is wireless, portable, battery-powered, and cell-phone operated, and it allows
      reliable detection in parts per billion (ppb) by volume-levels of BTEX in the
      presence of complex interferents. The hybrid device is suitable for occupational,
      environmental health, and epidemiological applications.

PMID- 24078794
TI  - Testing the Conjoint Influence of Impulsivity and Drinking Restraint on Alcohol
      Use Consequences in College Student Drinkers.
AB  - OBJECTIVES: Impulsivity and drinking restraint play a role in excessive drinking
      patterns and related negative consequences. Two domains of drinking restraint
      include preoccupation with thoughts of drinking (CEP) and attempts to control
      drinking (CBC), which differentially predict varying alcohol use outcomes in
      clinical and non-clinical samples. However, findings do not replicate across
      clinical, dependent samples and risky drinking young adults. This study examined
      the moderating role of dispositional impulsivity on the association between
      drinking restraint and alcohol consequences among college students to help
      clarify inconsistencies in the literature. METHODS: Data were collected from a
      sample of college student drinkers (N = 393) on drinking behavior in the past 90
      days, alcohol-related problems, dispositional impulsivity, and drinking
      restraint. RESULTS: The association between CBC and alcohol consequences was
      significantly stronger for those higher than lower in dispositional impulsivity,
      after controlling for the effects of alcohol consumption. No such relationship
      was found for those high in trait temptation. CONCLUSIONS: Alcohol consequences
      are greater among those who attempt to control their drinking and who act rashly
      and without consideration of future consequences; those who are high on trait
      temptation show no such relationship.

PMID- 24078795
TI  - Numerical investigation of heat transfer and friction factor characteristics in a
      circular tube fitted with V-cut twisted tape inserts.
AB  - Numerical investigation of the heat transfer and friction factor characteristics
      of a circular fitted with V-cut twisted tape (VCT) insert with twist ratio (y =
      2.93) and different cut depths (w = 0.5, 1, and 1.5 cm) were studied for laminar
      flow using CFD package (FLUENT-6.3.26). The data obtained from plain tube were
      verified with the literature correlation to ensure the validation of simulation
      results. Classical twisted tape (CTT) with different twist ratios (y = 2.93,
      3.91, 4.89) were also studied for comparison. The results show that the
      enhancement of heat transfer rate induced by the classical and V-cut twisted tape
      inserts increases with the Reynolds number and decreases with twist ratio. The
      results also revealed that the V-cut twisted tape with twist ratio y = 2.93 and
      cut depth w = 0.5 cm offered higher heat transfer rate with significant increases
      in friction factor than other tapes. In addition the results of V-cut twist tape
      compared with experimental and simulated data of right-left helical tape inserts
      (RLT), it is found that the V-cut twist tape offered better thermal contact
      between the surface and the fluid which ultimately leads to a high heat transfer
      coefficient. Consequently, 107% of maximum heat transfer was obtained by using
      this configuration. 

PMID- 24078796
TI  - Research on formation of microsatellite communication with genetic algorithm.
AB  - For the formation of three microsatellites which fly in the same orbit and
      perform three-dimensional solid mapping for terra, this paper proposes an
      optimizing design method of space circular formation order based on improved
      generic algorithm and provides an intersatellite direct spread spectrum
      communication system. The calculating equation of LEO formation flying satellite
      intersatellite links is guided by the special requirements of formation-flying
      microsatellite intersatellite links, and the transmitter power is also confirmed
      throughout the simulation. The method of space circular formation order
      optimizing design based on improved generic algorithm is given, and it can keep
      formation order steady for a long time under various absorb impetus. The
      intersatellite direct spread spectrum communication system is also provided. It
      can be found that, when the distance is 1 km and the data rate is 1 Mbps, the
      input wave matches preferably with the output wave. And LDPC code can improve the
      communication performance. The correct capability of (512, 256) LDPC code is
      better than (2, 1, 7) convolution code, distinctively. The design system can
      satisfy the communication requirements of microsatellites. So, the presented
      method provides a significant theory foundation for formation-flying and
      intersatellite communication. 

PMID- 24078797
TI  - Genesis analysis of high-gamma ray sandstone reservoir and its log evaluation
      techniques: a case study from the Junggar basin, northwest China.
AB  - In the Junggar basin, northwest China, many high gamma-ray (GR) sandstone
      reservoirs are found and routinely interpreted as mudstone non-reservoirs, with
      negative implications for the exploration and exploitation of oil and gas. Then,
      the high GR sandstone reservoirs' recognition principles, genesis, and log
      evaluation techniques are systematically studied. Studies show that the sandstone
      reservoirs with apparent shale content greater than 50% and GR value higher than
      110API can be regarded as high GR sandstone reservoir. The high GR sandstone
      reservoir is mainly and directly caused by abnormally high uranium enrichment,
      but not the tuff, feldspar or clay mineral. Affected by formation's high water
      sensitivity and poor borehole quality, the conventional logs can not recognize
      reservoir and evaluate the physical property of reservoirs. Then, the nuclear
      magnetic resonance (NMR) logs is proposed and proved to be useful in reservoir
      recognition and physical property evaluation. 

PMID- 24078798
TI  - Query-biased preview over outsourced and encrypted data.
AB  - For both convenience and security, more and more users encrypt their sensitive
      data before outsourcing it to a third party such as cloud storage service.
      However, searching for the desired documents becomes problematic since it is
      costly to download and decrypt each possibly needed document to check if it
      contains the desired content. An informative query-biased preview feature, as
      applied in modern search engine, could help the users to learn about the content
      without downloading the entire document. However, when the data are encrypted,
      securely extracting a keyword-in-context snippet from the data as a preview
      becomes a challenge. Based on private information retrieval protocol and the core
      concept of searchable encryption, we propose a single-server and two-round
      solution to securely obtain a query-biased snippet over the encrypted data from
      the server. We achieve this novel result by making a document (plaintext)
      previewable under any cryptosystem and constructing a secure index to support
      dynamic computation for a best matched snippet when queried by some keywords. For
      each document, the scheme has O(d) storage complexity and O(log(d/s) + s + d/s)
      communication complexity, where d is the document size and s is the snippet
      length. 

PMID- 24078799
TI  - Online Activities for Enhancing Sex Education Curricula: Preliminary Evidence on
      the Effectiveness of the Abstinence and Contraception Education Storehouse.
AB  - The purpose of this research was to conduct a preliminary evaluation of the
      Abstinence and Contraception Education Storehouse (ACES), a digital, classroom
      based resource designed to supplement existing sex education curricula with
      highly interactive materials such as video clips, multimedia polls and quizzes,
      and audiovisual demonstrations. 335 students ages 14-19 were randomly assigned to
      an ACES-based (treatment) or a standard (control) sex education curriculum. Data
      were collected at the onset of the intervention and 3-months after the completion
      of the intervention. Preliminary results were highly encouraging, with ACES
      participants who were sexually initiated at baseline reporting at the 3-month
      follow-up significant reductions in the number of times they had sex in the past
      four weeks. Both sexually initiated and non-sexually initiated youth who
      experienced the ACES curriculum also demonstrated greater intent to abstain from
      the sex during the follow-up period than those in the control group.

PMID- 24078800
TI  - At a crossroads: reentry challenges and healthcare needs among homeless female ex
      offenders.
AB  - The exponential increase in the number of women parolees and probationers in the
      last decade has made women the most rapidly growing group of offenders in the
      United States. The purpose of this descriptive, qualitative study is to
      understand the unique gendered experiences of homeless female ex-offenders, in
      the context of healthcare needs, types of health services sought, and gaps in
      order to help them achieve a smooth transition post prison release. Focus group
      qualitative methodology was utilized to engage 14 female ex-offenders enrolled in
      a residential drug treatment program in Southern California. The findings
      suggested that for homeless female ex-offenders, there are a myriad of healthcare
      challenges, knowledge deficits, and barriers to moving forward in life, which
      necessitates strategies to prevent relapse. These findings support the
      development of gender-sensitive programs for preventing or reducing drug and
      alcohol use, recidivism, and sexually transmitted infections among this hard-to
      reach population. 

PMID- 24078801
TI  - A DNA methylation prognostic signature of glioblastoma: identification of NPTX2
      PTEN-NF-kappaB nexus.
AB  - Glioblastoma (GBM) is the most common, malignant adult primary tumor with dismal
      patient survival, yet the molecular determinants of patient survival are poorly
      characterized. Global methylation profile of GBM samples (our cohort; n = 44)
      using high-resolution methylation microarrays was carried out. Cox regression
      analysis identified a 9-gene methylation signature that predicted survival in GBM
      patients. A risk-score derived from methylation signature predicted survival in
      univariate analysis in our and The Cancer Genome Atlas (TCGA) cohort.
      Multivariate analysis identified methylation risk score as an independent
      survival predictor in TCGA cohort. Methylation risk score stratified the patients
      into low-risk and high-risk groups with significant survival difference. Network
      analysis revealed an activated NF-kappaB pathway association with high-risk
      group. NF-kappaB inhibition reversed glioma chemoresistance, and RNA interference
      studies identified interleukin-6 and intercellular adhesion molecule-1 as key NF
      kappaB targets in imparting chemoresistance. Promoter hypermethylation of
      neuronal pentraxin II (NPTX2), a risky methylated gene, was confirmed by
      bisulfite sequencing in GBMs. GBMs and glioma cell lines had low levels of NPTX2
      transcripts, which could be reversed upon methylation inhibitor treatment. NPTX2
      overexpression induced apoptosis, inhibited proliferation and anchorage
      independent growth, and rendered glioma cells chemosensitive. Furthermore, NPTX2
      repressed NF-kappaB activity by inhibiting AKT through a p53-PTEN-dependent
      pathway, thus explaining the hypermethylation and downregulation of NPTX2 in NF
      kappaB-activated high-risk GBMs. Taken together, a 9-gene methylation signature
      was identified as an independent GBM prognosticator and could be used for GBM
      risk stratification. Prosurvival NF-kappaB pathway activation characterized high
      risk patients with poor prognosis, indicating it to be a therapeutic target.

PMID- 24078802
TI  - Genetic and pharmacologic inhibition of mTORC1 promotes EMT by a TGF-beta
      independent mechanism.
AB  - Epithelial-to-mesenchymal transition (EMT) is a transdifferentiation process that
      converts epithelial cells into highly motile mesenchymal cells. This physiologic
      process occurs largely during embryonic development but is aberrantly reactivated
      in different pathologic situations, including fibrosis and cancer. We conducted a
      siRNA screening targeted to the human kinome with the aim of discovering new EMT
      effectors. With this approach, we have identified mTOR complex 1 (mTORC1), a
      nutrient sensor that controls protein and lipid synthesis, as a key regulator of
      epithelial integrity. Using a combination of RNAi and pharmacologic approaches,
      we report here that inhibition of either mTOR or RPTOR triggers EMT in mammary
      epithelial cells. This EMT was characterized by the induction of the mesenchymal
      markers such as fibronectin, vimentin, and PAI-1, together with the repression of
      epithelial markers such as E-cadherin and ZO-3. In addition, mTORC1 blockade
      enhanced in vivo migratory properties of mammary cells and induced EMT
      independent of the TGF-beta pathway. Finally, among the transcription factors
      known to activate EMT, both ZEB1 and ZEB2 were upregulated following mTOR
      repression. Their increased expression correlated with a marked reduction in miR
      200b and miR-200c mRNA levels, two microRNAs known to downregulate ZEB1 and ZEB2
      expression. Taken together, our findings unravel a novel function for mTORC1 in
      maintaining the epithelial phenotype and further indicate that this effect is
      mediated through the opposite regulation of ZEB1/ZEB2 and miR-200b and miR-200c.
      Furthermore, these results suggest a plausible etiologic explanation for the
      progressive pulmonary fibrosis, a frequent adverse condition associated with the
      therapeutic use of mTOR inhibitors.

PMID- 24078803
TI  - MabCent: Arctic marine bioprospecting in Norway.
AB  - The deep waters surrounding the coastline of the northern parts of Norway
      represent an exciting biotope for marine exploration. Dark and cold Arctic water
      generates a hostile environment where the ability to adapt is crucial to
      survival. These waters are nonetheless bountiful and a diverse plethora of marine
      organisms thrive in these extreme conditions, many with the help of specialised
      chemical compounds. In comparison to warmer, perhaps more inviting shallower
      tropical waters, the Arctic region has not been as thoroughly investigated.
      MabCent is a Norwegian initiative based in Tromso that aims to change this. Since
      2007, scientists within MabCent have focussed their efforts on the study of
      marine organisms inhabiting the Arctic waters with the long term goal of novel
      drug discovery and development. The activities of MabCent are diverse and range
      from sampling the Arctic ice shelf to the chemical synthesis of promising
      secondary metabolites discovered during the screening process. The current review
      will present the MabCent pipeline from isolation to identification of new
      bioactive marine compounds via an extensive screening process. An overview of the
      main activities will be given with particular focus on isolation strategies,
      bioactivity screening and structure determination. Pitfalls, hard earned lessons
      and the results so far are also discussed.

PMID- 24078805
TI  - Gender inequality: Bad for men's health.
AB  - Men's increased risk of death in ART programmes in sub-Saharan Africa is widely
      reported but poorly understood. Some studies have attributed this risk to men's
      poorer health-seeking behaviour, which may prevent them from accessing ART, being
      adherent to treatment, or remaining in care. In a multicentre analysis of 46 201
      adults starting ART in urban and rural settings in South Africa, these factors
      only partly explained men's increased mortality while receiving ART. Importantly,
      the gender difference in mortality among patients receiving ART (31% higher for
      men than women) was substantially smaller than that among HIV-negative South
      Africans, where men had twice the risk of death compared with women. Yet, this
      extreme gender inequality in mortality, both within and outside of ART
      programmes, has not given rise to widespread action. Here it is argued that,
      despite their dominance in society, men may be subject to a wide range of unfair
      discriminatory practices, which negatively affect their health outcomes. The
      health needs of men and boys require urgent attention.

PMID- 24078806
TI  - Convergence analysis of particle swarm optimizer and its improved algorithm based
      on velocity differential evolution.
AB  - This paper presents an analysis of the relationship of particle velocity and
      convergence of the particle swarm optimization. Its premature convergence is due
      to the decrease of particle velocity in search space that leads to a total
      implosion and ultimately fitness stagnation of the swarm. An improved algorithm
      which introduces a velocity differential evolution (DE) strategy for the
      hierarchical particle swarm optimization (H-PSO) is proposed to improve its
      performance. The DE is employed to regulate the particle velocity rather than the
      traditional particle position in case that the optimal result has not improved
      after several iterations. The benchmark functions will be illustrated to
      demonstrate the effectiveness of the proposed method. 

PMID- 24078804
TI  - Viewpoints on Medical Image Processing: From Science to Application.
AB  - Medical image processing provides core innovation for medical imaging. This paper
      is focused on recent developments from science to applications analyzing the past
      fifteen years of history of the proceedings of the German annual meeting on
      medical image processing (BVM). Furthermore, some members of the program
      committee present their personal points of views: (i) multi-modality for imaging
      and diagnosis, (ii) analysis of diffusion-weighted imaging, (iii) model-based
      image analysis, (iv) registration of section images, (v) from images to
      information in digital endoscopy, and (vi) virtual reality and robotics. Medical
      imaging and medical image computing is seen as field of rapid development with
      clear trends to integrated applications in diagnostics, treatment planning and
      treatment.

PMID- 24078807
TI  - In Vivo Noninvasive Imaging of Healthy Lower Lip Mucosa: A Correlation Study
      between High-Definition Optical Coherence Tomography, Reflectance Confocal
      Microscopy, and Histology.
AB  - In recent years, technology has allowed the development of new diagnostic
      techniques which allow real-time, in vivo, noninvasive evaluation of
      morphological changes in tissue. This study compares and correlates the images
      and findings obtained by high-definition optical coherence tomography (HD-OCT)
      and reflectance confocal microscopy (RCM) with histology in normal healthy oral
      mucosa. The healthy lip mucosa of ten adult volunteers was imaged with HD-OCT and
      RCM. Each volunteer was systematically evaluated by RCM starting in the uppermost
      part of the epithelium down to the lamina propia. Afterwards, volunteers were
      examined with a commercially available full-field HD-OCT system using both the
      "slice" and the "en-face" mode. A "punch" biopsy of the lower lip mucosa was
      obtained and prepared for conventional histology. The architectural overview
      offered by "slice" mode HD-OCT correlates with histologic findings at low
      magnification. In the superficial uppermost layers of the epithelium, RCM imaging
      provided greater cellular detail than histology. As we deepened into the
      suprabasal layers, the findings are in accordance with physiological cellular
      differentiation and correlate with the images obtained from conventional
      histology. The combined use of these two novel non-invasive imaging techniques
      provides morphological imaging with sufficient resolution and penetration depth,
      resulting in quasihistological images. 

PMID- 24078808
TI  - Stretta Radiofrequency Treatment for GERD: A Safe and Effective Modality.
AB  - Gastroesophageal reflux disease is one of the leading gastrointestinal disorders.
      Current treatments include lifestyle modifications, pharmacological therapies,
      surgical fundoplications, and, more recently, endoscopic procedures. The rising
      concern of long-term side effects of the popular proton-pump inhibitors and the
      more recent evidence raising doubts about the durability of fundoplication have
      spurred reinterest in endoscopic procedures to treat reflux disorders. In the
      aftermath of several innovative antireflux procedures that were introduced and
      failed clinically or financially over the past decade, there is lingering
      confusion regarding the merits of the presently available interventions. This
      paper focuses on one endoscopic procedure, Stretta, which now enjoys the longest
      experience, a recent meta-analysis, and robust data supporting its safety,
      efficacy, and durability. Stretta reduces esophageal acid exposure, decreases the
      frequency of transient lower esophageal relaxation, increases patient
      satisfaction, decreases medication use, and improves quality of life. As such,
      this procedure remains a valuable nonsurgical treatment option in the management
      of gastroesophageal reflux disease. 

PMID- 24078809
TI  - A tree-like model for brain growth and structure.
AB  - The Flory-Stockmayer theory for the polycondensation of branched polymers,
      modified for finite systems beyond the gel point, is applied to the connection
      (synapses) of neurons, which can be considered highly branched "monomeric" units.
      Initially, the process is a linear growth and tree-like branching between
      dendrites and axons of nonself-neurons. After the gel point and at the maximum
      "tree" size, the tree-like model prescribes, on average, one pair of twin
      synapses per neuron. About 13% of neurons, "unconnected" to the maximum tree,
      migrate to the surface to form cortical layers. The number of synapses in each
      neuron may reach 10000, indicating a tremendous amount of flexible, redundant,
      and neuroplastic loop-forming linkages which can be preserved or pruned by
      experience and learning. 

PMID- 24078810
TI  - Exercise for hepatic fat accumulation in type 2 diabetic subjects.
AB  - Type 2 diabetes is characterized by frequent ectopic fat accumulation in several
      tissues and organs. In particular, a number of studies showed that these subjects
      frequently have hepatic fat accumulation, which may play a role in the metabolic
      abnormalities typical of diabetes and has been also linked to increased risk for
      cardiovascular disease. In the last decade, the effect of exercise on ectopic fat
      content of type 2 diabetic patients has raised growing interest. However, there
      are only a few small randomized controlled trials on this topic. Results from
      these intervention studies indicate that exercise training, independent of
      dietary modifications, may reduce hepatic fat content and serum transaminases in
      these patients, suggesting that exercise per se may be an effective strategy to
      be combined with the traditional dietary interventions. As regards the different
      training modalities, there is recent evidence that both aerobic and resistance
      exercise may equally reduce hepatic fat accumulation in type 2 diabetic subjects.
      However, information regarding the effect of exercise on liver histology and fat
      accumulation in other ectopic sites is still very limited. 

PMID- 24078811
TI  - Proteomics of uveal melanoma: a minireview.
AB  - Uveal melanoma (UM) continues to be associated with a high mortality rate of up
      to 50% due to metastatic spread primarily to the liver. Currently there are
      relatively effective treatments for the primary tumor, though the management of
      the metastatic disease remains inadequate. Conventional diagnostic tools have a
      low sensitivity for detecting metastasis, and early detection of metastatic
      spread would allow more treatment options that could ultimately increase survival
      of UM patients. Advanced proteomic methods have already helped to find potential
      biomarkers associated with UM pathogenesis and metastasis. In the present review
      we discuss the field of proteomics in relation to studies elucidating biomarkers
      of UM, where proteins such as S-100 beta , osteopontin (OPN), and melanoma
      inhibitory activity (MIA) have been shown to be associated with metastasis. 

PMID- 24078812
TI  - Advances in optical adjunctive AIDS for visualisation and detection of oral
      malignant and potentially malignant lesions.
AB  - Traditional methods of screening for oral potentially malignant disorders and
      oral malignancies involve a conventional oral examination with digital palpation.
      Evidence indicates that conventional examination is a poor discriminator of oral
      mucosal lesions. A number of optical aids have been developed to assist the
      clinician to detect oral mucosal abnormalities and to differentiate benign
      lesions from sinister pathology. This paper discusses advances in optical
      technologies designed for the detection of oral mucosal abnormalities. The
      literature regarding such devices, VELscope and Identafi, is critically analysed,
      and the novel use of Narrow Band Imaging within the oral cavity is also
      discussed. Optical aids are effective in assisting with the detection of oral
      mucosal abnormalities; however, further research is required to evaluate the
      usefulness of these devices in differentiating benign lesions from potentially
      malignant and malignant lesions. 

PMID- 24078814
TI  - Circulating Levels of Soluble Receptor Activator of NF- kappa B Ligand and Matrix
      Metalloproteinase 3 (and Their Antagonists) in Asian Indian Patients with
      Ankylosing Spondylitis.
AB  - Background. Bone loss in ankylosing spondylitis may be related to inflammation.
      Data from previous studies on circulating levels of sRANKL, OPG, MMP3, and TIMP
      is inconsistent; thus this study is planned to look at this aspect in Asian
      Indian patients. Methods. Cross-sectional study included patients with ankylosing
      spondylitis and age- and gender-similar controls. Serum levels of sRANKL, OPG,
      MMP-3, and TIMP-1 were measured by ELISA. Results. Included 85 patients (M : F =
      82 : 3) having mean age (+/-SD) 33.0 +/- 10.0 years and disease duration 11.3 +/-
      7.3 years. BASDAI, BASFI, BASMI, and ESR were 4.0 +/- 2.2, 3.9 +/- 2.8, 3.0 +/-
      2.8, and 59.2 +/- 31.2, respectively. Patients had higher mean (+/-SD) OPG level
      (649.7 +/- 286.8, 389.3 +/- 244.8 pg/mL, P < 0.001). However, there was no
      difference in sRANKL (349.2 +/- 872.0, 554.7 +/- 1850.1, P = ns). Serum MMP-3
      (91.4 +/- 84.7, 55.9 +/- 37.1 ng/mL, P < 0.01) and TIMP-1 (520.6 +/- 450.7, 296.5
      +/- 114.2 ng/mL, P < 0.001) levels were higher in patients; however, there was no
      difference in MMP-3/TIMP-1 ratio. Conclusion. Circulating levels of OPG were
      higher; however, there was no difference in sRANKL in Asian Indian ankylosing
      spondylitis patients. Although both MMP-3 and TIMP-1 were raised, their ratio was
      not different from that of controls. 

PMID- 24078813
TI  - Regulation of the Ras-MAPK and PI3K-mTOR Signalling Pathways by Alternative
      Splicing in Cancer.
AB  - Alternative splicing is a fundamental step in regulation of gene expression of
      many tumor suppressors and oncogenes in cancer. Signalling through the Ras-MAPK
      and PI3K-mTOR pathways is misregulated and hyperactivated in most types of
      cancer. However, the regulation of the Ras-MAPK and PI3K-mTOR signalling pathways
      by alternative splicing is less well established. Recent studies have shown the
      contribution of alternative splicing regulation of these signalling pathways
      which can lead to cellular transformation, cancer development, and tumor
      maintenance. This review will discuss findings in the literature which describe
      new modes of regulation of components of the Ras-MAPK and PI3K-mTOR signalling
      pathways by alternative splicing. We will also describe the mechanisms by which
      signals from extracellular stimuli can be communicated to the splicing machinery
      and to specific RNA-binding proteins that ultimately control exon definition
      events. 

PMID- 24078815
TI  - Pure Red Cell Aplasia with Adult Onset Still's Disease.
AB  - Adult Onset Still's Disease (AOSD) is a rare inflammatory syndrome mostly seen in
      young adults. Known for its wide range of clinical manifestations, AOSD often
      presents with nonremitting systemic signs and symptoms. Many rare case
      associations have been described with AOSD, but only few with pure red cell
      aplasia (PRCA). We are presenting a fourth known case of a young female adult
      with AOSD and PRCA in the literature. 

PMID- 24078817
TI  - A simple methodology for conversion of mouse monoclonal antibody to human-mouse
      chimeric form.
AB  - Passive immunotherapy has mainly been used as a therapy against cancer and
      inflammatory conditions. Recent studies have shown that monoclonal antibody-(mAb
      ) based passive immunotherapy is a promising approach to combat virus infection.
      Specific mouse mAbs can be routinely generated in large amounts with the use of
      hybridoma technology but these cannot be used for therapy in human beings due to
      their immunogenicity. Therefore, the development of chimeric and humanized mAbs
      is important for therapeutic purpose. This is facilitated by a variety of
      molecular techniques like recombinant DNA technology and the better understanding
      of the structure and function of antibody. The human-mouse chimeric forms allow
      detailed analysis of the mechanism of inhibition and the potential for
      therapeutic applications. Here, a step-by-step description of the conversion
      process will be described. The commercial availability of the reagents required
      in each step means that this experimentation can be easily set up in research
      laboratories. 

PMID- 24078818
TI  - Microglia in development and disease.

PMID- 24078816
TI  - Sphingolipids and brain resident macrophages in neuroinflammation: an emerging
      aspect of nervous system pathology.
AB  - Sphingolipid metabolism is deeply regulated along the differentiation and
      development of the central nervous system (CNS), and the expression of a peculiar
      spatially and temporarily regulated sphingolipid pattern is essential for the
      maintenance of the functional integrity of the nervous system. Microglia are
      resident macrophages of the CNS involved in general maintenance of neural
      environment. Modulations in microglia phenotypes may contribute to pathogenic
      forms of inflammation. Since defects in macrophage/microglia activity contribute
      to neurodegenerative diseases, it will be essential to systematically identify
      the components of the microglial cell response that contribute to disease
      progression. In such complex processes, the sphingolipid systems have recently
      emerged to play important roles, thus appearing as a key new player in CNS
      disorders. This review provides a rationale for harnessing the sphingolipid
      metabolic pathway as a potential target against neuroinflammation. 

PMID- 24078820
TI  - Different Surface Electromyography of Propagated Sensation along Meridians
      Produced by Acupuncturing Quchi Acupoint (LI11) or Control Points.
AB  - This study investigated the propagated sensation along meridians (PSM) produced
      respectively by acupuncture at a specific acupoint of right-side Quchi (LI11), a
      nonacupoint on meridian (control meridian point), and neither meridian nor
      acupoint (control point). All the stimulated points were on the right
      brachioradialis along the large intestine meridian of hand Yangming. Surface
      electromyography (sEMG) was used to reflect the activity of the brachioradialis
      along the large intestine meridian of hand Yangming. The PSM rate of LI11
      (59.21%) and the control meridian point (53.95%) were significantly higher than
      the control point (38.16%) (P < 0.05). After acupuncture, the brachioradialis
      sEMG amplitude was 5.08 +/- 2.93 uV at LI11, 3.08 +/- 1.18 uV at the control
      point, and 2.77 +/- 1.36 uV at the control meridian point. The amplitude of LI11
      was significantly higher than both the control meridian point and the control
      point (P < 0.05). When the sEMG activity of brachioradialis returned to the
      stable base line, brachioradialis sEMG duration at LI11 (265 +/- 87.87 s) was
      significantly longer than that at the control meridian point (91.69 +/- 42.98 s)
      and the control point (83.31 +/- 32.76 s) (P < 0.05). In conclusion, acupuncture
      activated PSM at all points but showed an acupoint specificity at LI11 and a
      meridian specificity at the control meridian point. 

PMID- 24078819
TI  - Exploring the Needs and Concerns of Women with Early Breast Cancer during
      Chemotherapy: Valued Outcomes during a Course of Traditional Acupuncture.
AB  - Women diagnosed with breast cancer experience symptom clusters in addition to
      existential issues from a life-threatening diagnosis during chemotherapy. A
      complementary therapy, such as traditional acupuncture (TA) with its whole-person
      orientation, may help to modify these effects, alongside inducing other patient
      benefits. Exploring the needs and concerns of women and perceived benefits of TA
      would add to knowledge about its integrative treatment potential. Methods. A
      longitudinal qualitative study recruited fourteen women to receive up to ten
      sessions of TA during chemotherapy. They were interviewed before, during, and
      after chemotherapy. Two practitioners of TA delivered treatment and were
      interviewed before and after the study, and kept treatment logs and diaries.
      Interviews were recorded and transcribed, and the data were analysed using
      grounded theory. Findings. Both broad and specific benefits were reported by the
      women; a highly valued outcome was enabling coping through the alleviation of
      symptoms and increased well-being. Practitioners dealt with the presented symptom
      clusters facilitating outcome patterns, including and beyond individual symptom
      changes. Further research on TA as a flexible intervention able to respond to the
      changing needs and concerns of woman during chemotherapy along with the measure
      of such outcome patterns is warranted. 

PMID- 24078821
TI  - Effect of Electroacupuncture Intervention on Expression of CGRP, SP, COX-1, and
      PGE2 of Dorsal Portion of the Cervical Spinal Cord in Rats with Neck-Incision
      Pain.
AB  - The present study was aimed to determine if cervicospinal substance P (SP) and
      its neurokinin-1 receptor (NK-1R), calcitonin gene-related peptide (CGRP),
      cyclooxygenase-1 (COX-1), and prostaglandin E2 (PGE2) were involved in
      electroacupuncture (EA) analgesia in neck-incision pain rats. EA intervention was
      applied to bilateral Futu (LI18), Hegu (LI4)-Neiguan (PC6), and Zusanli (ST36)
      Yanglingquan (GB34) for 30 min. Cervicospinal SP and CGRP immunoactivity was
      detected by immunofluorescence technique, NK-1R and COX-1 protein and mRNA
      expression levels were determined using Western blot and real-time PCR,
      respectively, and PGE2 content was measured using ELISA. Outcomes indicated that
      EA of EA-LI18 and LI4-PC6 (not ST36-GB34) significantly suppressed neck-incision
      induced decrease of thermal pain threshold (P < 0.05). EA stimulation of LI18 and
      LI4-PC6 markedly inhibited neck-incision induced upregulation of SP and CGRP
      immunoactivity, NK-1 R and COX-1 mRNA and protein expression levels, as well as
      the increase of PGE2 content in the dorsal cervicospinal cord (P < 0.05). These
      findings showed that LI18 and LI4-PC6 EA stimulation-induced downregulation of
      SP, CGRP, NK-1R, COX-1, and PGE2 levels in the dorsal cervicospinal cord may
      contribute to their effects in relieving neck-incision pain. This study
      highlights the targets of EA intervention for reducing post-thyroid-surgery pain
      for the first time. 

PMID- 24078823
TI  - Effectiveness of traditional Japanese herbal (kampo) medicine, daiobotanpito, in
      combination with antibiotic therapy in the treatment of acute diverticulitis: a
      preliminary study.
AB  - In traditional Japanese herbal (Kampo) medicine, daiobotanpito (DBT) or Da Huang
      Mu Dan Tang in Chinese has been used in medical treatment of acute diverticulitis
      for many years based on the experience. Our aim was to investigate whether the
      treatment of acute diverticulitis can be treated with intravenous antibiotics
      plus orally administrated DBT than intravenous antibiotics alone. A retrospective
      nonrandomized open-label trial was established to compare patients with acute
      diverticulitis who received oral DBT associated with intravenous antibiotics with
      those who received intravenous antibiotic alone. We included 34 patients, eleven
      patients in group 1 with DBT and 23 patients in group 2 without DBT. Both groups
      were comparable in patient demographics and clinical characteristics. There was a
      significantly better outcome in the group treated with DBT than in the group
      without DBT when comparing duration of fever, abdominal pain, and antibiotics
      administration. A trend toward a day shorter mean hospital stay and fasting was
      seen in group 1, although this did not reach statistical significance. In
      conclusion, most patients with acute diverticulitis can be managed safely with
      oral DBT. Although randomized, double-blind study must be done, we could show the
      possibility to use daiobotanpito as an additional option in treating acute
      diverticulitis. 

PMID- 24078822
TI  - Standardized Extract of Bacopa monniera Attenuates Okadaic Acid Induced Memory
      Dysfunction in Rats: Effect on Nrf2 Pathway.
AB  - The aim of the present study is to investigate the effect of standardized extract
      of Bacopa monnieri (memory enhancer) and Melatonin (an antioxidant) on nuclear
      factor erythroid 2 related factor 2 (Nrf2) pathway in Okadaic acid induced memory
      impaired rats. OKA (200 ng) was administered intracerebroventricularly (ICV) to
      induce memory impairment in rats. Bacopa monnieri (BM-40 and 80 mg/kg) and
      Melatonin (20 mg/kg) were administered 1 hr before OKA injection and continued
      daily up to day 13. Memory functions were assessed by Morris water maze test on
      days 13-15. Rats were sacrificed for biochemical estimations of oxidative stress,
      neuroinflammation, apoptosis, and molecular studies of Nrf2, HO1, and GCLC
      expressions in cerebral cortex and hippocampus brain regions. OKA caused a
      significant memory deficit with oxidative stress, neuroinflammation, and neuronal
      loss which was concomitant with attenuated expression of Nrf2, HO1, and GCLC.
      Treatment with BM and Melatonin significantly improved memory dysfunction in OKA
      rats as shown by decreased latency time and path length. The treatments also
      restored Nrf2, HO1, and GCLC expressions and decreased oxidative stress,
      neuroinflammation, and neuronal loss. Thus strengthening the endogenous defense
      through Nrf2 modulation plays a key role in the protective effect of BM and
      Melatonin in OKA induced memory impairment in rats. 

PMID- 24078824
TI  - Protective effect of qiliqiangxin capsule on energy metabolism and myocardial
      mitochondria in pressure overload heart failure rats.
AB  - Qiliqiangxin capsule (QL) was developed under the guidance of TCM theory of
      collateral disease and had been shown to be effective and safe for the treatment
      of heart failure. The present study explored the role of and mechanism by which
      the herbal compounds QL act on energy metabolism, in vivo, in pressure overload
      heart failure. SD rats received ascending aorta constriction (TAC) to establish a
      model of myocardial hypertrophy. The animals were treated orally for a period of
      six weeks. QL significantly inhibited cardiac hypertrophy due to ascending aortic
      constriction and improved hemodynamics. This effect was linked to the expression
      levels of the signaling factors in connection with upregulated energy and the
      regulation of glucose and lipid substrate metabolism and with a decrease in
      metabolic intermediate products and the protection of mitochondrial function. It
      is concluded that QL may regulate the glycolipid substrate metabolism by
      activating AMPK/PGC-1 alpha axis and reduce the accumulation of free fatty acids
      and lactic acid, to protect cardiac myocytes and mitochondrial function. 

PMID- 24078825
TI  - Moving with ease: feldenkrais method classes for people with osteoarthritis.
AB  - Objective. To investigate the effects of Feldenkrais Method classes on gait,
      balance, function, and pain in people with osteoarthritis. Design. Prospective
      study with pre-/postmeasures. Setting. Community. Participants. Convenience
      sample of 15 community-dwelling adults with osteoarthritis (mean age 67 years)
      attending Feldenkrais Method classes. Intervention. Series of Feldenkrais Method
      classes, two classes/week for 30 weeks. MAIN OUTCOME MEASURES: Western Ontario
      and McMaster Universities osteoarthritis scale, Human Activity Profile, stair
      climbing test, 6-minute walk test, timed up-and-go test, Four Square Step Test
      (4SST), gait analysis, and assessment of quality of life (AQoL). Results.
      Participants improved on the 4SST and on some gait parameters. They also reported
      a greater ease of movement. Conclusions. A 30-week series of Feldenkrais classes
      held twice per week was feasible in the community setting. The lessons led to
      improvements in performance of the four square step test and changes in gait.

PMID- 24078826
TI  - Optimizing prescription of chinese herbal medicine for unstable angina based on
      partially observable markov decision process.
AB  - Objective. Initial optimized prescription of Chinese herb medicine for unstable
      angina (UA). Methods. Based on partially observable Markov decision process model
      (POMDP), we choose hospitalized patients of 3 syndrome elements, such as qi
      deficiency, blood stasis, and turbid phlegm for the data mining, analysis, and
      objective evaluation of the diagnosis and treatment of UA at a deep level in
      order to optimize the prescription of Chinese herb medicine for UA. Results. The
      recommended treatment options of UA for qi deficiency, blood stasis, and phlegm
      syndrome patients were as follows: Milkvetch Root + Tangshen + Indian Bread +
      Largehead Atractylodes Rhizome (ADR = 0.96630); Danshen Root + Chinese Angelica +
      Safflower + Red Peony Root + Szechwan Lovage Rhizome Orange Fruit (ADR = 0.76);
      Snakegourd Fruit + Longstamen Onion Bulb + Pinellia Tuber + Dried Tangerine peel
      + Largehead Atractylodes Rhizome + Platycodon Root (ADR = 0.658568). Conclusion.
      This study initially optimized prescriptions for UA based on POMDP, which can be
      used as a reference for further development of UA prescription in Chinese herb
      medicine. 

PMID- 24078827
TI  - The effects of adding elements of zinc and magnesium on ag-cu eutectic alloy for
      warming acupuncture.
AB  - The warming acupuncture for hyperthermia therapy is made of STS304. However, its
      needle point cannot be reached to a desirable temperature due to heat loss caused
      by low thermal conductivity, and the quantification of stimulation condition and
      the effective standard establishment of warming acupuncture are required as a
      heat source. Accordingly, in this study, after Ag-Cu alloys with different
      composition ratios were casted and then mixed with additives to improve their
      physical and mechanical properties, the thermal conductivity and biocompatibility
      of the alloy specimens were evaluated for selecting suitable material. Ag-Cu
      binary alloys and ternary alloys added 5 wt% Zn or 2 wt% Mg were casted and then
      cold drawn to manufacture needles for acupuncture, and their physical properties,
      thermal conductivity, and biocompatibility were evaluated for their potential use
      in warming acupuncture. The results of this study showed that the physical and
      mechanical properties of the Ag-Cu alloys were improved by additives and that the
      thermal conductivity, machinability, and biocompatibility of the Ag-Cu alloys
      were improved by Mg addition. 

PMID- 24078828
TI  - Eupafolin and Ethyl Acetate Fraction of Kalanchoe gracilis Stem Extract Show
      Potent Antiviral Activities against Enterovirus 71 and Coxsackievirus A16.
AB  - Enterovirus 71 (EV71) and coxsackievirus A16 (CoxA16) are main pathogens of hand
      foot-and-mouth disease, occasionally causing aseptic meningitis and encephalitis
      in tropical and subtropical regions. Kalanchoe gracilis, Da-Huan-Hun, is a
      Chinese folk medicine for treating pain and inflammation, exhibiting antioxidant
      and anti-inflammatory activities. Our prior report (2012) cited K. gracilis leaf
      extract as moderately active against EV71 and CoxA16. This study further rates
      antienteroviral potential of K. gracilis stem (KGS) extract to identify potent
      antiviral fractions and components. The extract moderately inhibits viral
      cytopathicity and virus yield, as well as in vitro replication of EV71 (IC50 =
      75.18  MU g/mL) and CoxA16 (IC50 = 81.41  MU g/mL). Ethyl acetate (EA) fraction
      of KGS extract showed greater antiviral activity than that of n-butanol or
      aqueous fraction: IC50 values of 4.21  MU g/mL against EV71 and 9.08  MU g/mL
      against CoxA16. HPLC analysis, UV-Vis absorption spectroscopy, and plaque
      reduction assay indicate that eupafolin is a vital component of EA fraction
      showing potent activity against EV71 (IC50 = 1.39  MU M) and CoxA16 (IC50 = 5.24 
      MU M). Eupafolin specifically lessened virus-induced upregulation of IL-6 and
      RANTES by inhibiting virus-induced ERK1/2, AP-1, and STAT3 signals. Anti
      enteroviral potency of KGS EA fraction and eupafolin shows the clinical potential
      against EV71 and CoxA16 infection. 

PMID- 24078829
TI  - The key role of cultural preservation in maize diversity conservation in the
      argentine yungas.
AB  - Farmers' decisions on what to grow and why can contribute in understanding the
      conservation of agrobiodiversity. Culture and ethnicity are indicated as first
      class factors leading preservation of heirloom cultivars but this has been little
      considered in studies examining factors that influence the loss or preservation
      of agrobiodiversity. We propose that corn's ethnotaxa of less diverse uses, which
      are also key partners in local cultural reproduction, are usually cultivated by a
      few households. We analyse if there is a relationship between uses and richness
      of cultivated ethnotaxa at household level and describe corn's medicinal and
      ritual uses. We found 25 cultivated ethnotaxa, heterogeneously distributed in the
      region, and we also found that ethnotaxa with less diverse uses are cultivated in
      fewer households. We identified that, at regional scale, richness is related with
      food use diversity. The most frequently cited medicinal uses were urinary and
      tract infections, diarrhoea, and liver disorders. Medicinal recipes involve
      combinations with other elements. Maize is an indispensable resource in the
      rituals that propitiate productive activity, to augur prosperity or misfortune
      according to signals. We have identified the vulnerability in preserving the
      richness of corn in the region and the factors that shape its cultivation at
      different scales. 

PMID- 24078830
TI  - Bisdemethoxycurcumin Increases Sirt1 to Antagonize t-BHP-Induced Premature
      Senescence in WI38 Fibroblast Cells.
AB  - Curcuminoids are well known for their capabilities to combat risk factors that
      are associated with ageing and cellular senescence. Recent reports have
      demonstrated that curcuminoids can extend the lifespan of model organisms.
      However, the underlying mechanisms by which these polyphenic compounds exert
      these beneficial effects remain unknown. In this study, t-BHP-induced premature
      senescence model in human fibroblasts was chosen to explore the protective
      effects of a curcuminoid, bisdemethoxycurcumin (BDMC), on cellular senescence.
      The results demonstrated that BDMC attenuated oxidative stress-induced senescence
      like features which include the induction of an enlarged cellular appearance,
      higher frequency of senescence-associated beta -galactosidase staining activity,
      appearance of senescence-associated heterochromatic foci in nuclei, decrease in
      proliferation capability, and alteration in related molecules such as p16 and
      retinoblastoma protein. Notably, we found that BDMC treatment activated
      Sirt1/AMPK signaling pathway. Moreover, downregulating Sirt1 by the
      pharmacological inhibitor nicotianamine or small interfering RNA blocked BDMC
      mediated protection against t-BHP-mediated decrease in proliferation. These
      results suggested that BDMC prevented t-BHP-induced cellular senescence, and BDMC
      induced Sirt1 may be a mechanism mediating its beneficial effects. 

PMID- 24078831
TI  - Interleukin-6 cytokine: a multifunctional glycoprotein for cancer.
AB  - Interleukin 6 is a multifunctional cytokine. Its increased levels have been
      associated with elevated cancer risk, and also these levels have been found to be
      a prognostic factor for several cancer types. In addition, increased levels have
      been found in coronary heart disease, insulin resistant patients, advance stage
      cancer patients, atopy/asthma and in patients with blood circulating
      micrometastasis. Additionally several studies with different types of cancers
      have been performed to identify the correlation between interleukin-6 levels,
      stage, treatment response and severity of symptoms. The influence of interleukin
      6 is performed mainly through the janus kinase-signal transducer and activator of
      transcription-zinc finger protein 1-2 signaling pathway. As a result, the
      increased levels of interleukin-6 are responsible for enhanced neo-angiogenesis,
      inhibition of cancer cell apoptosis and deregulation of the control mechanisms in
      the microenvironment. In addition, increased levels of inteleukin-6 have been
      found to increase the production of collagen and a-actin which induce
      interstitial lung disease. In the current mini review we will present information
      regarding the interleukin-6 and published results in several cancer studies and
      finally we will comment in future treatment approaches blocking this cytokine in
      cancer patients. 

PMID- 24078832
TI  - Circadian models of serum potassium, sodium, and calcium concentrations in
      healthy individuals and their application to cardiac electrophysiology
      simulations at individual level.
AB  - In the article a brief description of the biological basis of the regulation of
      human biological clocks was presented in order to introduce the role of circadian
      rhythms in physiology and specifically in the pharmacological translational tools
      based on the computational physiology models to motivate the need to provide
      models of circadian fluctuation in plasma cations. The main aim of the study was
      to develop statistical models of the circadian rhythm of potassium, sodium, and
      calcium concentrations in plasma. The developed ion models were further tested by
      assessing their influence on QT duration (cardiac endpoint) as simulated by the
      biophysically detailed models of human left ventricular cardiomyocyte. The main
      results are model equations along with an electronic supplement to the article
      that contains a fully functional implementation of all models. 

PMID- 24078834
TI  - Self-terminating diffraction gates femtosecond X-ray nanocrystallography
      measurements.
AB  - X-ray free-electron lasers have enabled new approaches to the structural
      determination of protein crystals that are too small or radiation-sensitive for
      conventional analysis1. For sufficiently short pulses, diffraction is collected
      before significant changes occur to the sample, and it has been predicted that
      pulses as short as 10 fs may be required to acquire atomic-resolution structural
      information1-4. Here, we describe a mechanism unique to ultrafast, ultra-intense
      X-ray experiments that allows structural information to be collected from
      crystalline samples using high radiation doses without the requirement for the
      pulse to terminate before the onset of sample damage. Instead, the diffracted X
      rays are gated by a rapid loss of crystalline periodicity, producing apparent
      pulse lengths significantly shorter than the duration of the incident pulse. The
      shortest apparent pulse lengths occur at the highest resolution, and our
      measurements indicate that current X-ray free-electron laser technology5 should
      enable structural determination from submicrometre protein crystals with atomic
      resolution.

PMID- 24078835
TI  - Design and development of topoisomerase inhibitors using molecular modelling
      studies.
AB  - Topoisomerase inhibitors are used as anticancer and antibacterial agents. A
      series of novel 2,4,6-tri-substituted pyridine derivatives reported as
      topoisomerase inhibitors were used for quantitative structure-activity
      relationship (QSAR) study. In order to understand the structural requirement of
      these topoisomerase inhibitors, a ligand-based pharmacophore and atom-based 3D
      QSAR model have been developed. A five-point pharmacophore with one hydrophobic
      group (H4), four aromatic rings (R5, R6, R7 and R8) was obtained. The
      pharmacophore hypothesis yielded a 3D-QSAR model with good partial least-square
      (PLS) statistic results. The training set correlation is characterized by PLS
      factors (r (2) = 0.7892, SD = 0.2948, F = 49.9, P = 1.379). The test set
      correlation is characterized by PLS factors (q (2) = 0.7776, root mean squared
      error = 0.2764, Pearson R = 0.8926). The docking study revealed the binding
      orientations of these inhibitors at active site amino acid residues of
      topoisomerases enzyme. The results of pharmacophore hypothesis and 3D-QSAR
      provided the detail structural insights as well as highlighted the important
      binding features of novel 2,4,6-tri-substituted pyridine derivatives and can be
      developed as potent topoisomerase inhibitors. FigureKey structural requirement
      for topoisomerase activity. 

PMID- 24078836
TI  - Conflicts of interest--an ever present challenge.

PMID- 24078838
TI  - Medical students' attitudes to and contact with the pharmaceutical industry: a
      survey at eight German university hospitals.
AB  - BACKGROUND: Drug companies maintain close contact with physicians. We studied the
      extent to which medical students are already in contact with drug companies, and
      their attitudes toward them. METHODS: An anonymous questionnaire containing 74
      questions was distributed to 1151 medical students at eight German universities.
      1038 (90.3%) of the questionnaires were filled out, returned, and evaluated.
      RESULTS: 12.1% of the students had never received any kind of gift from a drug
      company or participated in any drug company-sponsored event. 13.0% had received
      at least one sponsored lunch, and 24.6% had attended at least one sponsored
      lecture or CME event. 65.6% had received at least one non-informational gift,
      50.8% an informational gift, 39.3% a reprint, and 8.6% a drug sample. 39.8%
      considered sponsored lectures informative and helpful, but simultaneously judged
      the presentation of content as biased. 45.6% and 49.7% of students, respectively,
      considered it all right to accept gifts because their influence was minimal in
      any case or because they considered themselves in a bad financial situation.
      24.6% of the students thought gifts would influence their future prescribing
      behavior, while 45.1% thought gifts would influence their classmates' future
      prescribing behavior (p<0.001 for this difference). CONCLUSION: Medical students
      have extensive contact with the pharmaceutical industry even before they are out
      of medical school. Therefore, the medical school curriculum should include
      information about the strategies drug companies use to influence physicians'
      prescribing behavior, so that medical students can develop an appropriately
      critical attitude.

PMID- 24078837
TI  - Does the pharmaceutical industry influence guidelines?: two examples from
      Germany.
AB  - BACKGROUND: The recommendations in clinical guidelines are based on clinical
      trial findings and expert opinion. The influence of drug companies on these two
      factors is illustrated with two examples. METHODS: A judicially ordered expert
      review revealed that the market authorization holder (MAH) of gabapentin
      manipulated study data. Gabapentin was, therefore, chosen as an example for this
      article to analyze whether manipulated data serve as a basis for recommendations
      in German clinical guidelines. A search was carried out for manipulated
      publications on gabapentin that found their way into guidelines published by the
      Association of Scientific Medical Societies in Germany (Arbeitsgemeinschaft der
      Wissenschaftlichen Medizinischen Fachgesellschaften, AWMF). To analyze the
      possible effects of financial ties between guideline authors and drug companies,
      the S3 guideline on the treatment of psoriasis vulgaris with efalizumab was
      compared with guidelines whose authors had no conflicts of interest. One of the
      authors of this article had noted variable prescribing practices for psoriasis
      among dermatologists while carrying out an economic assessment for a German state
      Association of Statutory Health Insurance Physicians. RESULTS: The data that had
      been manipulated by the MAH of gabapentin served as a basis for recommendations
      to prescribe gabapentin in guidelines that were published by the AWMF. Efalizumab
      was judged more favorably in the S3 guideline than in a guideline issued by the
      National Institute of Health and Care Excellence: for example, the evidence for
      it was judged as good, the use of efalizumab for induction and combination
      therapy in psoriasis vulgaris was recommended, and efalizumab was said to improve
      patients' health-related quality of life. CONCLUSION: Public access to all trial
      data must be ensured so that independent evaluations are possible. We take the
      view that the responsibility for creating guidelines should be borne by authors
      and organizations that do not have any conflicts of interest.

PMID- 24078839
TI  - The treatment of proximal humeral fracture in adults.
AB  - BACKGROUND: The incidence of proximal humeral fractures lies between 105 and 342
      per 100 000 persons per year. Around the world, this type of fracture remains a
      major challenge for treating surgeons. While non-displaced fractures can be
      managed conservatively, displaced ones are often treated surgically. METHODS:
      Selective literature review. RESULTS: There are still no evidence-based schemes
      or guidelines for the treatment of proximal humeral fractures, and very few
      prospective randomized trials are available. The few that have been published
      recently show a trend in favor of conservative treatment, but they were carried
      out on small groups of patients and their findings are not directly
      generalizable. For younger patients, the goal of treatment is generally
      anatomical repositioning and osteosynthetic stabilization; for older patients,
      primary treatment with a prosthesis is a further option. Depending on the mode of
      treatment, complications can arise such as shoulder stiffness, necrosis of the
      humeral head, pain, infection, loss of reposition, and "cutting out." CONCLUSION:
      Current evidence supports the individualized treatment of proximal humeral
      fractures. Treatment decisions must always be made jointly with the patient in
      consideration of his or her individual needs and characteristics. Particularly
      for elderly patients, the possibility of conservative treatment should be
      carefully considered. If conservative treatment is not possible, then the type of
      operation performed should also be a function of the surgeon's individual skills
      and experience with particular types of implant.

PMID- 24078840
TI  - Correspondence (letter to the editor): Lack of precision in colloquial language
      results in incorrect therapeutic recommendation.

PMID- 24078841
TI  - Correspondence (reply): In reply.

PMID- 24078842
TI  - Correspondence (letter to the editor): Remember self-help.

PMID- 24078843
TI  - Correspondence (letter to the editor): The therapeutic objective: reducing the
      stress caused by tinnitus.

PMID- 24078844
TI  - Correspondence (letter to the editor): Research is needed.

PMID- 24078845
TI  - Correspondence (letter to the editor): Psychiatrists are not the first port of
      call.

PMID- 24078846
TI  - Correspondence (reply): In reply.

PMID- 24078848
TI  - Correspondence (letter to the editor): Numerous competing interests.

PMID- 24078847
TI  - The CARE guidelines: consensus-based clinical case reporting guideline
      development.
AB  - BACKGROUND: A case report is a narrative that describes, for medical, scientific,
      or educational purposes, a medical problem experienced by one or more patients.
      Case reports written without guidance from reporting standards are insufficiently
      rigorous to guide clinical practice or to inform clinical study design. Our
      primary objective was to develop, disseminate, and implement systematic reporting
      guidelines for case reports. METHODS: We used a three-phase consensus process
      consisting of (1) pre-meeting literature review and interviews to generate items
      for the reporting guidelines, (2) a face-to-face consensus meeting to draft the
      reporting guidelines, and (3) post-meeting feedback, review, and pilot testing,
      followed by finalization of the case reporting guidelines. RESULTS: This
      consensus process involved 27 participants and resulted in a 13-item checklist-a
      reporting guideline for case reports. The primary items of the checklist are
      title, key words, abstract, introduction, patient information, clinical findings,
      timeline, diagnostic assessment, therapeutic interventions, follow-up and
      outcomes, discussion, patient perspective, and informed consent. CONCLUSIONS: We
      believe the implementation of the CARE (CAse REporting) guidelines by medical
      journals will improve the completeness and transparency of published case reports
      and that the systematic aggregation of information from case reports will inform
      clinical study design, provide early signals of effectiveness and harms, and
      improve healthcare delivery.

PMID- 24078849
TI  - Correspondence (letter to the editor): One-sided publication.

PMID- 24078850
TI  - Correspondence (letter to the editor): Regular muscle activity.

PMID- 24078851
TI  - Correspondence (letter to the editor): Professional and ethical criticism.

PMID- 24078852
TI  - Correspondence (reply): In reply.

PMID- 24078853
TI  - Correspondence (letter to the editor): Treatment option not mentioned.

PMID- 24078854
TI  - Correspondence (reply): In reply.

PMID- 24078855
TI  - Degenerative lumbar spinal stenosis in older people: current treatment options.
AB  - BACKGROUND: Degenerative lumbar spinal stenosis is increasingly being diagnosed
      in persons over age 65. In 2011, 55 793 older people with this condition were
      treated as inpatients in German hospitals. Among physicians, there is much
      uncertainty about the appropriate treatment strategy. METHOD: Selective
      literature review. RESULTS: Lumbar spinal stenosis in older people is
      characterized by spinal claudication and neurological deficits. A precise
      clinical history and physical examination and ancillary radiological studies are
      the necessary prerequisites for treatment. Magnetic resonance imaging is the
      radiological study of choice. Conservative treatment consists of physiotherapy,
      drugs, and local injections; various surgical treatments can be considered,
      depending on the severity of the problem. The main purpose of surgery is to
      decompress the spinal canal. If the lumbar spine is demonstrably unstable, an
      instrumented fusion should be performed in addition. There is, however, only
      moderately good evidence supporting the superiority of surgery over conservative
      treatment. In a prospective study, the complication rate of purely decompressive
      surgery was found to be 18%. The utility of the current operative techniques
      cannot be definitively assessed, because they are applied to a wide variety of
      patients in different stages of the disease and at different degrees of severity,
      and the reported results are thus not comparable from one trial to another.
      CONCLUSION: No evidence-based recommendation on the diagnosis and treatment of
      lumbar spinal stenosis in older people can be formulated at present because of
      the lack of pertinent randomized trials.

PMID- 24078856
TI  - Retention loss of resin based fissure sealants - a valid predictor for clinical
      outcome?
AB  - PURPOSE: The null-hypothesis that retention loss of resin fissure sealants
      predicts caries manifestation no more accurately than random values was tested.
      METHODS: Systematic reviews were checked and electronic databases searched for
      clinical trials. Trials reporting on the retention of resin sealants and caries
      occurrence in permanent molar teeth, with minimum 24-month follow-up period, were
      included. Extracted data: number of sealed teeth, number of teeth without
      completely retained sealants, number of sealed teeth with caries. The number of
      teeth with complete sealant retention and absence of carious lesions/cavities was
      calculated; the predictive outcomes: true/false positive; false/true negative
      were established. Random values were generated as control-data. Diagnostic Odds
      ratios (DOR) were computed and tested for statistical difference. Summary
      Receiver Operating Characteristic curves were plotted. RESULTS: 95 trials were
      found. Median DOR values were 1.21 and 0.28 for test- and control data,
      respectively. Wilcoxon test (z = 0.56; p = 0.58) and Sign test (z = 1.38; p =
      0.17) results were statistically non-significant. The null-hypothesis was not
      rejected. CONCLUSIONS: Predictions based on the retention loss of resin sealants,
      regarding caries manifestation, was no more accurate than random guesses. Sealant
      retention loss appears not to be a valid predictor for clinical outcome.

PMID- 24078857
TI  - Tele-ICU: Efficacy and Cost-Effectiveness Approach of Remotely Managing the
      Critical Care.
AB  - Tele-ICU has an off-site command center in which a critical care team
      (intensivists and critical care nurses) is connected with patients in distance
      intensive care units (ICUs) through a real-time audio, visual and electronic
      means and health information is exchanged. The aim of this paper is to review
      literature to explore the available studies related to efficacy and cost
      effectiveness of Tele-ICU applications and to study the possible barriers to
      broader adoption. While studies draw conclusions on cost based on the mortality
      and Length of Stay (LOS), actual cost was not reported. Another problem in the
      studies was the lack of consistent measurement, reporting and adjustment for
      patient severity. From the data available, Tele-ICU seems to be a promising path,
      especially in the United States where there is a limited number of board
      certified intensivists. 

PMID- 24078858
TI  - Delay in Seeking Care for Sexually Transmitted Diseases in Young Men and Women
      Attending a Public STD Clinic.
AB  - BACKGROUND: Delay in seeking care for sexually transmitted diseases (STDs) has
      adverse consequences for both the individual and population. We sought to
      identify factors associated with delay in seeking care for STDs. METHODS:
      Subjects included 300 young men and women (aged 15-24) attending an urban STD
      clinic for a new STD-related problem due to symptoms or referral for an STD
      screening. Subjects completed a structured interview that evaluated STD history,
      attitudes and beliefs about STDs, depression, substance use, and other factors
      possibly associated with delay. Delay was defined as waiting > 7 days to seek and
      obtain care for STDs. RESULTS: Nearly one-third of participants delayed seeking
      care for > 7 days. Significant predictors for delay included self-referral for
      symptoms as the reason for visit (OR 5.3, 95% CI: 2.58 - 10.98), and the beliefs
      "my partner would blame me if I had an STD" (OR 2.44, 95% CI: 1.30 - 4.60) and
      "it's hard to find time to get checked for STDs" (OR 3.62, 95% CI: 1.95 - 6.69),
      after adjusting for age, race, sex, and other factors. Agreeing with the
      statement "would use a STD test at home if one were available" was associated
      with a decrease in delay (OR 0.24, 95% CI: 0.09 - 0.60). CONCLUSIONS: Many young
      persons delay seeking care for STDs for a number of reasons. Strategies to
      improve STD care-seeking include encouragement of symptomatic persons to seek
      medical care more rapidly, reduction of social stigmas, and improved access to
      testing options.

PMID- 24078859
TI  - BAYESIAN INFERENCE AND MODEL CHOICE IN A HIDDEN STOCHASTIC TWO-COMPARTMENT MODEL
      OF HEMATOPOIETIC STEM CELL FATE DECISIONS.
AB  - Despite rapid advances in experimental cell biology, the in vivo behavior of
      hematopoietic stem cells (HSC) cannot be directly observed and measured.
      Previously we modeled feline hematopoiesis using a two-compartment hidden Markov
      process that had birth and emigration events in the first compartment. Here we
      perform Bayesian statistical inference on models which contain two additional
      events in the first compartment in order to determine if HSC fate decisions are
      linked to cell division or occur independently. Pareto Optimal Model Assessment
      approach is used to cross check the estimates from Bayesian inference. Our
      results show that HSC must divide symmetrically (i.e., produce two HSC daughter
      cells) in order to maintain hematopoiesis. We then demonstrate that the augmented
      model that adds asymmetric division events provides a better fit to the
      competitive transplantation data, and we thus provide evidence that HSC fate
      determination in vivo occurs both in association with cell division and at a
      separate point in time. Last we show that assuming each cat has a unique set of
      parameters leads to either a significant decrease or a nonsignificant increase in
      model fit, suggesting that the kinetic parameters for HSC are not unique
      attributes of individual animals, but shared within a species.

PMID- 24078860
TI  - A regulatory role of NAD redox status on flavin cofactor homeostasis in S.
      cerevisiae mitochondria.
AB  - Flavin adenine dinucleotide (FAD) and nicotinamide adenine dinucleotide (NAD) are
      two redox cofactors of pivotal importance for mitochondrial functionality and
      cellular redox balance. Despite their relevance, the mechanism by which
      intramitochondrial NAD(H) and FAD levels are maintained remains quite unclear in
      Saccharomyces cerevisiae. We investigated here the ability of isolated
      mitochondria to degrade externally added FAD and NAD (in both its reduced and
      oxidized forms). A set of kinetic experiments demonstrated that mitochondrial FAD
      and NAD(H) destroying enzymes are different from each other and from the already
      characterized NUDIX hydrolases. We studied here, in some detail, FAD
      pyrophosphatase (EC 3.6.1.18), which is inhibited by NAD(+) and NADH according to
      a noncompetitive inhibition, with Ki values that differ from each other by an
      order of magnitude. These findings, together with the ability of mitochondrial
      FAD pyrophosphatase to metabolize endogenous FAD, presumably deriving from
      mitochondrial holoflavoproteins destined to degradation, allow for proposing a
      novel possible role of mitochondrial NAD redox status in regulating FAD
      homeostasis and/or flavoprotein degradation in S. cerevisiae. 

PMID- 24078861
TI  - Potentiation of antibiofilm activity of amphotericin B by superoxide dismutase
      inhibition.
AB  - This study demonstrates a role for superoxide dismutases (Sods) in governing
      tolerance of Candida albicans biofilms to amphotericin B (AmB). Coincubation of
      C. albicans biofilms with AmB and the Sod inhibitors N,N'-diethyldithiocarbamate
      (DDC) or ammonium tetrathiomolybdate (ATM) resulted in reduced viable biofilm
      cells and increased intracellular reactive oxygen species levels as compared to
      incubation of biofilm cells with AmB, DDC, or ATM alone. Hence, Sod inhibitors
      can be used to potentiate the activity of AmB against C. albicans biofilms. 

PMID- 24078862
TI  - Diaryl- and triaryl-pyrrole derivatives: inhibitors of the MDM2-p53 and MDMX-p53
      protein-protein interactions?Electronic supplementary information (ESI)
      available: Experimental details for compound synthesis, analytical data for all
      compounds and intermediates. Details for the biological evaluation. Further
      details for the modeling. Table of combustion analysis data. See DOI:
      10.1039/c3md00161jClick here for additional data file.
AB  - Screening identified 2-(3-((4,6-dioxo-2-thioxotetrahydropyrimidin-5(2H)
      ylidene)methyl)-2,5-dimethyl-1H-pyrrol-1-yl)-4,5,6,7-tetrahydrobenzo[b]thiophene
      3-carbonitrile as an MDM2-p53 inhibitor (IC50 = 12.3 MUM). MDM2-p53 and MDMX-p53
      activity was seen for 5-((1-(4-chlorophenyl)-2,5-diphenyl-1H-pyrrol-3
      yl)methylene)-2-thioxodihydropyrimidine-4,6(1H,5H)-dione (MDM2 IC50 = 0.11 MUM;
      MDMX IC50 = 4.2 MUM) and 5-((1-(4-nitrophenyl)-2,5-diphenyl-1H-pyrrol-3
      yl)methylene)pyrimidine-2,4,6(1H,3H,5H)-trione (MDM2 IC50 = 0.15 MUM; MDMX IC50 =
      4.2 MUM), and cellular activity consistent with p53 activation in MDM2 amplified
      cells. Further SAR studies demonstrated the requirement for the triarylpyrrole
      moiety for MDMX-p53 activity but not for MDM2-p53 inhibition.

PMID- 24078864
TI  - Fluorescent materials for pH sensing and imaging based on novel 1,4-diketopyrrolo
      [3,4-c]pyrrole dyes?Electronic supplementary information (ESI) available: NMR and
      MS spectra, further sensor characteristics and sensor long-time performance. See
      DOI: 10.1039/c3tc31130aClick here for additional data file.
AB  - New optical pH-sensors relying on 1,4-diketopyrrolo-[3,4-c]pyrroles (DPPs) as
      fluorescent pH-indicators are presented. Different polymer hydrogels are useful
      as immobilization matrices, achieving excellent sensitivity and good brightness
      in the resulting sensor. The operational pH can be tuned over a wide range (pH 5
      12) by selecting the fine structure of the indicator and the matrix. A
      ratiometric sensor in the form of nanoparticles is also presented. It is suitable
      for RGB camera readout, and its practical applicability for fluorescence imaging
      in microfluidic systems is demonstrated. The indicators are synthesized starting
      from the commercially available DPP pigments by a straightforward concept
      employing chlorosulfonation and subsequent reaction with amines. Their
      sensitivity derives from two distinct mechanisms. At high pH (>9), they exhibit a
      remarkable alteration of both absorption and fluorescence spectra due to
      deprotonation of the lactam nitrogen atoms. If a phenolic group is introduced,
      highly effective fluorescence quenching at near-neutral pH occurs due to
      photoinduced electron transfer (PET) involving the phenolate form.

PMID- 24078865
TI  - Lentiviral vectors for cancer immunotherapy and clinical applications.
AB  - The success of immunotherapy against infectious diseases has shown us the
      powerful potential that such a treatment offers, and substantial work has been
      done to apply this strategy in the fight against cancer. Cancer is however a
      fiercer opponent than pathogen-caused diseases due to natural tolerance towards
      tumour associated antigens and tumour-induced immunosuppression. Recent gene
      therapy clinical trials with viral vectors have shown clinical efficacy in the
      correction of genetic diseases, HIV and cancer. The first successful gene therapy
      clinical trials were carried out with onco(gamma-)retroviral vectors but
      oncogenesis by insertional mutagenesis appeared as a serious complication.
      Lentiviral vectors have emerged as a potentially safer strategy, and recently the
      first clinical trial of patients with advanced leukemia using lentiviral vectors
      has proven successful. Additionally, therapeutic lentivectors have shown clinical
      efficacy for the treatment of HIV, X-linked adrenoleukodystrophy, and beta
      thalassaemia. This review aims at describing lentivectors and how they can be
      utilized to boost anti-tumour immune responses by manipulating the effector
      immune cells. 

PMID- 24078866
TI  - Simultaneous Detection of Different MicroRNA Types Using the ZIP-Code Array
      System.
AB  - MicroRNAs (miRNAs) are important negative regulators of gene expression. Their
      implication in tumorigenesis is based on their dysregulation in many human cancer
      diseases. Interestingly, in tumor cells, an altered ratio of precursor and mature
      miRNA levels has been described. Consequently, differences in miRNA type levels
      have a high potential as biomarkers and comparative high-throughput-based
      detection might permit a more accurate characterization of subtypes, especially
      in the case of very heterogeneous tumor entities. Several molecular methods exist
      for the detection of mature and precursor miRNAs. DNA microarrays are
      predestinated as a high-throughput method for comprehensive miRNA detection in
      tumors. However, the simultaneous array-based detection of both these miRNA types
      is limited because the mature miRNA sequence is identically present in both
      forms. Here we present a ZIP-code DNA microarray-based system in combination with
      a novel labeling approach, which enables the simultaneous detection of precursor
      and mature miRNAs in one single experiment. Using synthetic miRNA templates, we
      demonstrate the specificity of the method for the different miRNA types, as well
      as the detection range up to four orders of magnitude. Moreover, mature and
      precursor miRNAs were detected and validated in human tumor cells. 

PMID- 24078867
TI  - Short- and midterm results between laparoscopic Roux-en-Y gastric bypass and
      laparoscopic sleeve gastrectomy for the treatment of morbid obesity.
AB  - BACKGROUND: Laparoscopic Roux-en-Y gastric bypass (LRYGB) is one of the most
      widely used bariatric procedures today, and laparoscopic sleeve gastrectomy (LSG)
      as a single-stage procedure for the treatment of morbid obesity is becoming
      increasingly popular in Europe. The aim of this study was to compare short- and
      midterm results between LRYGB and LSG. METHODS: An observational retrospective
      study from a database of patients undergoing LRYGB and LSG between January 2008
      and June 2011. Seventy patients (mean age 39 years) were included. Patients were
      followed at 6, 12, and 18 months. Operative time, length of stay, weight loss,
      comorbidity improvement or resolution, postoperative complications,
      reinterventions and mortality were evaluated. RESULTS: Thirty-six LRYGB and 34
      LSG were included. Mean operative time of LSG was 106 min while LRYGB was 196 min
      (P < 0.001). Differences in length of stay, early and late complications, and
      improvement or resolution in comorbidities were not significant (P > 0.05).
      Eighteen months after surgery, average excess weight loss was 77.6% in LRYGB and
      57.1% in LSG (P = 0.003). There was no surgery-related mortality. CONCLUSIONS:
      Both LRYGB and LSG are safe procedures that provide good results in weight loss
      and resolution of comorbidities at 18 months.

PMID- 24078869
TI  - Epileptic encephalopathies in children.

PMID- 24078868
TI  - Preliminary Evidence for Feasibility, Use, and Acceptability of Individualized
      Texting for Adherence Building for Antiretroviral Adherence and Substance Use
      Assessment among HIV-Infected Methamphetamine Users.
AB  - The feasibility, use, and acceptability of text messages to track methamphetamine
      use and promote antiretroviral treatment (ART) adherence among HIV-infected
      methamphetamine users was examined. From an ongoing randomized controlled trial,
      30-day text response rates of participants assigned to the intervention
      (individualized texting for adherence building (iTAB), n = 20) were compared to
      those in the active comparison condition (n = 9). Both groups received daily
      texts assessing methamphetamine use, and the iTAB group additionally received
      personalized daily ART adherence reminder texts. Response rate for
      methamphetamine use texts was 72.9% with methamphetamine use endorsed 14.7% of
      the time. Text-derived methamphetamine use data was correlated with data from a
      structured substance use interview covering the same time period (P < 0.05). The
      iTAB group responded to 69.0% of adherence reminder texts; among those responses,
      81.8% endorsed taking ART medication. Standardized feedback questionnaire
      responses indicated little difficulty with the texts, satisfaction with the
      study, and beliefs that future text-based interventions would be helpful.
      Moreover, most participants believed the intervention reduced methamphetamine use
      and improved adherence. Qualitative feedback regarding the intervention was
      positive. Future studies will refine and improve iTAB for optimal acceptability
      and efficacy. This trial is registered with ClinicalTrials.gov NCT01317277. 

PMID- 24078870
TI  - The protease activated receptor 2 (PAR2) polymorphic variant F240S constitutively
      activates PAR2 receptors and potentiates responses to small-molecule PAR2
      agonists.
AB  - AC-55541 [N-[[1-(3-bromo-phenyl)-eth-(E)-ylidene-hydrazinocarbonyl]-(4-oxo-3,4
      dihydro-phthalazin-1-yl)-methyl]-benzamide] and AC-264613 [2-oxo-4
      phenylpyrrolidine-3-carboxylic acid [1-(3-bromo-phenyl)-(E/Z)-ethylidene]
      hydrazide] are the first two small-molecule agonists described for the G protein
      coupled receptor protease-activated receptor 2 (PAR2), but whether they activate
      PAR2 through a similar mechanism as its tethered peptide ligand or soluble
      peptide mimetics of its tethered peptide ligand is unclear. Extracellular loop 2
      (ECL2) has been shown to play a critical role in the activation mechanism of
      PAR2. Therefore, we constructed a series of PAR2 receptors mutated in ECL2,
      including a previously described polymorphic variant of PAR2 (F240S), and
      compared AC-55541 and AC-264613 to SLIGRL and a potent analog of SLIGRL called 2
      furoyl LIGRLO in a series of functional assays, including cellular proliferation,
      phosphatidylinositol hydrolysis, and beta-arrestin recruitment assays.
      Surprisingly, receptors with the F240S mutation were constitutively active in all
      functional assays tested. Furthermore, AC-55541 and AC-264613 were potentiated
      over 30-fold at the receptors with the F240S mutation, whereas SLIGRL and 2
      furoyl LIGRLO were much less affected. In contrast, mutagenesis of charged
      residues in ECL2 confirmed their important role in the actions of peptide
      agonists of PAR2, whereas these mutations did not significantly affect activation
      of PAR2 by AC-55541 or AC-264613. These results suggest that F240S PAR2 receptors
      may be useful in screens to detect novel small-molecule PAR2 modulators and that
      further work on the biological importance of the F240S PAR2 variant is warranted.

PMID- 24078871
TI  - Older persons' experiences of depressive ill-health and family support.
AB  - The aim of this study was to explore experiences of the meaning of family support
      among older persons with depressive ill-health. Data were collected from twenty
      nine participants through semistructured interviews and analysed using
      interpretative hermeneutic and reflective methodology. The findings revealed a
      main theme, hovering between feelings of belongingness and aloneness in
      relationships with family members, based on two themes: a sense of being worthy
      and a sense of being unworthy. Experiences of support and lack of support from
      family members were not opposites but connected in internal relationships and can
      be pictured as a movement on a continuum of ambiguity. Family support promotes
      the emotional needs of older persons with depressive ill-health to be confirmed.
      The family plays a vital role, not always by direct assistance, but indirectly by
      supporting the older person's own "guiding principles" for managing her/his
      situation. The feelings of aloneness as well as shame and guilt at poor or absent
      family responsiveness should be adequately addressed. Innovative nursing care can
      lead to improvement by focusing on acquiescence to the older person's life
      situation. 

PMID- 24078872
TI  - Drug Resistance among Pulmonary Tuberculosis Patients in Calabar, Nigeria.
AB  - Background. This study aimed to determine the pattern of drug susceptibility to
      first-line drugs among pulmonary TB patients in two hospitals in Calabar,
      Nigeria. Methods. This was a descriptive cross-sectional study carried out
      between February 2011 and April 2012. Sputum samples from consecutive TB patients
      in Calabar were subjected to culture on Lowenstein-Jensen (LJ) slopes followed by
      drug susceptibility testing (DST). The DST was performed on LJ medium by the
      proportion method. Results. Forty-two of the 100 Mycobacterium tuberculosis
      strains were found to be resistant to at least one drug. Resistance to only one
      drug (monoresistance) was found in 17 patients. No strains with monoresistance to
      rifampicin were found. Resistance to two drugs was found in 22 patients, while
      one patient was resistant to both three and four drugs. MDR TB was seen in 4%
      (4/100). The independent variables of HIV serology and sex were not significantly
      associated with resistance (P > 0.05). Conclusion. There was a high prevalence of
      anti-TB drug resistance in Calabar. 

PMID- 24078873
TI  - Utilization of CT Pulmonary Angiography in Suspected Pulmonary Embolism in a
      Major Urban Emergency Department.
AB  - Objectives. We conducted a study to answer 3 questions: (1) is CT pulmonary
      angiography (CTPA) overutilized in suspected pulmonary embolism (PE)? (2) What
      alternative diagnoses are provided by CTPA? (3) Can CTPA be used to evaluate
      right ventricular dilatation (RVD)? Methods. We retrospectively reviewed the
      clinical information of 231 consecutive emergency department patients who
      underwent CTPA for suspected PE over a one-year period. Results. The mean age of
      our patients was 53 years, and 58.4% were women. The prevalence of PE was 20.7%.
      Among the 136 patients with low clinical probability of PE, a d-dimer test was
      done in 54.4%, and it was normal in 24.3%; none of these patients had PE. The
      most common alternative findings on CTPA were emphysema (7.6%), pneumonia (7%),
      atelectasis (5.5%), bronchiectasis (3.8%), and congestive heart failure (3.3%).
      The sensitivity and negative predictive value of CTPA for (RVD) was 92% and 80%,
      respectively. Conclusions. PE could have been excluded without CTPA in ~1 out of
      4 patients with low clinical probability of PE, if a formal assessment of
      probability and d-dimer test had been done. In patients without PE, CTPA did not
      provide an alternative diagnosis in 65%. In patients with PE, CTPA showed the
      potential to evaluate RVD. 

PMID- 24078875
TI  - Diagnosis and progression of sacroiliitis in repeated sacroiliac joint computed
      tomography.
AB  - Objective. To assess the clinical utility of repeat sacroiliac joint computed
      tomography (CT) in sacroiliitis by assessing the proportion of patients changing
      from normal to pathologic at CT and to which degree there is progression of
      established sacroiliitis at repeat CT. Methods. In a retrospective analysis of
      334 patients (median age 34 years) with symptoms suggestive of inflammatory back
      pain, CT had been performed twice, in 47 of these thrice, and in eight patients
      four times. The studies were scored as normal, equivocal, unilateral
      sacroiliitis, or bilateral sacroiliitis. Results. There was no change in 331 of
      389 repeat examinations. Ten patients (3.0%) had progressed from normal or
      equivocal to unilateral or bilateral sacroiliitis. Of 43 cases with sacroiliitis
      on the first study, 36 (83.7%) progressed markedly. Two normal cases had changed
      to equivocal. Eight equivocal cases were classified as normal on the repeat
      study. In further two patients, only small changes within the scoring grade
      equivocal were detected. Conclusions. CT is a valuable examination for diagnosis
      of sacroiliitis, but a repeated examination detects only a few additional cases
      of sacroiliitis. Most cases with already established sacroiliitis showed
      progression of disease. 

PMID- 24078876
TI  - Effectiveness of a novel device in the reduction of cesarean deliveries.
AB  - Objective. To test the hypothesis that the use of the HEM-AVERT Perianal
      Stabilizer will result in a reduction of cesarean births and shorter duration of
      second-stage labor. Study Design. In a prospective controlled trial, 102 women
      scheduled for vaginal delivery were randomized to either the HEM-AVERT
      investigational device or control group. Ninety eight (98) patients completed the
      study. A chi-square test was used to evaluate the difference in the number of
      cesarean deliveries between the investigational and control groups. Duration of
      second-stage labor was assessed as a secondary outcome. Results. Six (6) of the
      50 patients in the investigational group (12%) failed to deliver vaginally and
      required cesarean delivery. Comparatively, 19 of the 48 control patients (39.6%)
      required cesarean delivery. Duration of second-stage labor was shorter in the
      investigational group, but the difference was not statistically significant.
      Results from 4 patients were excluded due to protocol violations. Conclusion. The
      HEM-AVERT device effectively reduced the incidence rate of cesarean deliveries in
      the investigational group when compared to women who delivered without use of the
      device. This trial is registered with ClinicalTrials.gov NCT01739543. 

PMID- 24078877
TI  - Protective effects of Korean red ginseng against radiation-induced apoptosis in
      human HaCaT keratinocytes.
AB  - Radiation-induced oral mucositis is a dose-limiting toxic side effect for
      patients with head and neck cancer. Numerous attempts at improving radiation
      induced oral mucositis have not produced a qualified treatment. Ginseng
      polysaccharide has multiple immunoprotective effects. Our aim was to investigate
      the effectiveness of Korean red ginseng (KRG) on radiation-induced damage in the
      human keratinocyte cell line HaCaT and in an in vivo zebrafish model. Radiation
      inhibited HaCaT cell proliferation and migration in a cell viability assay and
      wound healing assay, respectively. KRG protected against these effects. KRG
      attenuated the radiation-induced embryotoxicity in the zebrafish model.
      Irradiation of HaCaT cells caused apoptosis and changes in mitochondrial membrane
      potential (MMP). KRG inhibited the radiation-induced apoptosis and intracellular
      generation of reactive oxygen species (ROS), and stabilized the radiation-induced
      loss of MMP. Western blots revealed KRG-mediated reduced expression of ataxia
      telangiectasia mutated protein (ATM), p53, c-Jun N-terminal kinase (JNK), p38 and
      cleaved caspase-3, compared with their significant increase after radiation
      treatment. The collective results suggest that KRG protects HaCaT cells by
      blocking ROS generation, inhibiting changes in MMP, and inhibiting the caspase,
      ATM, p38 and JNK pathways. 

PMID- 24078879
TI  - Antimutagenic and Antiapoptotic Effects of Aqueous Root Extract of Inula racemosa
      Hook. f. on 4-NQO-Induced Genetic Damage in Mice.
AB  - The present study was performed as part of an attempt to authenticate the use of
      Inula racemosa root extract as traditional medicine in India by experimentally
      investigating their protective effects on 4-nitroquinoline-1-oxide (4-NQO)
      induced DNA damage and apoptosis in mice bone marrow cells. Aqueous root extract
      (ARE) of Inula racemosa (100, 200 and 400 mg/kg bw) with and without 4-NQO along
      with vehicle control (H2O) were administered orally for five consecutive days. 4
      NQO (7.5 mg/kg bw) was injected intraperitoneally to the mice on the sixth day.
      After 24 h, the animals were sacrificed and extracted bone marrow cells were used
      for micronuclei and apoptotic analysis. Antiapoptotic effect of ARE (400 mg/kg
      bw) was measured by the use of Annexin V-FITC assay kit. 4-NQO generated the
      frequency of micronucleated polychromatic erythrocytes (MnPCEs) by about 4.7
      times the control value, 14.29 MnPCEs/2500 PCEs. Pretreatment with ARE
      significantly reduced the MnPCEs frequency (39-72%) with respect to their doses,
      and increased PCEs/NCEs ratio was observed over the 4-NQO alone. 4-NQO-induced
      total apoptotic cells were about 12% over the control which was significantly (P
      < 0.05) brought down to 3.5% by pretreatment with 400 mg/kg bw of ARE. This was
      the first report that recorded the protective effects of I. racemosa on 4-NQO
      induced DNA damage and apoptosis in mice bone marrow cells. 

PMID- 24078878
TI  - Comparing CT perfusion with oxygen partial pressure in a rabbit VX2 soft-tissue
      tumor model.
AB  - The aim of this study was to evaluate the oxygen partial pressure of the rabbit
      model of the VX2 tumor using a 64-slice perfusion CT and to compare the results
      with that obtained using the oxygen microelectrode method. Perfusion CT was
      performed for 45 successfully constructed rabbit models of a VX2 brain tumor. The
      perfusion values of the brain tumor region of interest, the blood volume (BV),
      the time to peak (TTP) and the peak enhancement intensity (PEI) were measured.
      The results were compared with the partial pressure of oxygen (PO2) of that
      region of interest obtained using the oxygen microelectrode method. The perfusion
      values of the brain tumor region of interest in 45 successfully constructed
      rabbit models of a VX2 brain tumor ranged from 1.3-127.0 (average, 21.1 +/- 26.7
      ml/min/ml); BV ranged from 1.2-53.5 ml/100g (average, 22.2 +/- 13.7 ml/100g); PEI
      ranged from 8.7-124.6 HU (average, 43.5 +/- 28.7 HU); and TTP ranged from 8.2
      62.3 s (average, 38.8 +/- 14.8 s). The PO2 in the corresponding region ranged
      from 0.14-47 mmHg (average, 16 +/- 14.8 mmHg). The perfusion CT positively
      correlated with the tumor PO2, which can be used for evaluating the tumor hypoxia
      in clinical practice. 

PMID- 24078880
TI  - Study on situational influences perceived in nursing discipline on health
      promotion: a qualitative study.
AB  - Introduction and Objectives. Nurses, as behavioral models, play a key role in
      health promotion, and their attitudes towards health promotion highly influence
      their health and performance. The aim of this study is to explore nursing
      students' perception of studies in nursing discipline as a situational influence
      on health promotion. Materials and Methods. This study was conducted using
      directed content analysis, by means of 20 deep semistructured interviews with
      nursing students. The participants were selected on purposive sampling. Data was
      analyzed by the qualitative content analysis method. All interviews were
      recorded, transcribed, and reviewed, and all codes were extracted and summarized.
      The codes were subcategorized on the basis of centralization and were categorized
      after review of subcategories, and finally, a theme was determined. Findings. The
      theme of nursing discipline's situational influence on nursing students' health
      promotion was revealed. This theme consisted of "choosing the field,"
      "unfavorable environmental factors," "negative impacts of studies in nursing
      discipline on health," "positive effects of studies in nursing discipline on
      health", "needs," "attractiveness (aesthetics)," and "coping with negative
      situational influences in nursing discipline." Conclusion. The perception of
      studies in nursing discipline as a health-promoting behavior is under influence
      of social environment. Considering the importance of the students' positive
      perception of the existing situation, it is essential to pay attention to their
      attitudes and perceptions so that they can provide better services to patients. 

PMID- 24078882
TI  - Correlation of tinnitus loudness and onset duration with audiological profile
      indicating variation in prognosis.
AB  - Purpose. Subjective tinnitus has different forms and degrees of severity. Many
      studies in the literature have assessed psychoacoustic characteristics of
      tinnitus but hardly any of them had focused on the association of audiological
      profile with onset duration and loudness perception. The aim of this study was to
      evaluate existence of any association between tinnitus loudness/onset duration
      and audiological profile to explain differences in prognosis. Method. Study
      design was prospective. The sample consisted of 26 subjects having tinnitus,
      which was divided into tinnitus and nontinnitus ears. Audiological profile
      included pure-tone audiometry, speech audiometry, tympanometry, acoustic reflex
      test, and auditory evoked potentials (early and middle latency). Unpaired t-test
      was applied to compare two subgroups. Correlation and association between
      tinnitus onset duration/loudness perception and audiological profile were also
      assessed by calculating Spearman's coefficient and Fischer exact value. Results.
      The two subgroups had significant differences for pure-tone and speech audiometry
      hearing thresholds. A significant association was observed between the high
      frequency/extended high frequency and tinnitus loudness/onset duration.
      Conclusion. The changes in hearing thresholds and auditory pathway are associated
      with an increase in tinnitus loudness and its onset duration. This knowledge
      would be helpful to differentiate between severity and chronicity of the patients
      for planning therapeutic management and predicting prognosis. 

PMID- 24078881
TI  - Lesion-induced alterations in astrocyte glutamate transporter expression and
      function in the hippocampus.
AB  - Astrocytes express the sodium-dependent glutamate transporters GLAST and GLT-1,
      which are critical to maintain low extracellular glutamate concentrations. Here,
      we analyzed changes in their expression and function following a mechanical
      lesion in the CA1 area of organotypic hippocampal slices. 6-7 days after lesion,
      a glial scar had formed along the injury site, containing strongly activated
      astrocytes with increased GFAP and S100 beta immunoreactivity, enlarged somata,
      and reduced capability for uptake of SR101. Astrocytes in the scar's periphery
      were swollen as well, but showed only moderate upregulation of GFAP and S100 beta
      and efficiently took up SR101. In the scar, clusters of GLT-1 and GLAST
      immunoreactivity colocalized with GFAP-positive fibers. Apart from these, GLT-1
      immunoreactivity declined with increasing distance from the scar, whereas GLAST
      expression appeared largely uniform. Sodium imaging in reactive astrocytes
      indicated that glutamate uptake was strongly reduced in the scar but maintained
      in the periphery. Our results thus show that moderately reactive astrocytes in
      the lesion periphery maintain overall glutamate transporter expression and
      function. Strongly reactive astrocytes in the scar, however, display clusters of
      GLAST and GLT-1 immunoreactivity together with reduced glutamate transport
      activity. This reduction might contribute to increased extracellular glutamate
      concentrations and promote excitotoxic cell damage at the lesion site. 

PMID- 24078883
TI  - Clinical study of graft selection in malaysian rhinoplasty patients.
AB  - Graft selection remains the greatest challenge for surgeons performing
      rhinoplasty. The preferred choice thus far for nasal reconstruction would be
      autograft compared to allograft due to its lower rate of infection and extrusion
      as it does not induce an immune response. We have evaluated 26 patients who
      underwent open structured rhinoplasty at our center and compared our experience
      regarding the operative technique, graft availability, indications, and
      limitations. The racial distribution was 18 Indians, 5 Chinese, and 3 Malays with
      a mean age, hospitalization, and followup of 30.5 years, 16.9 months, and 4.4
      days, respectively. Majority of the patients (57.6%) presented with twisted nose
      and 30.7% of the patients presented with history of nasal trauma. All the
      patients had deviated septum of varying severity. The most common graft used was
      quadrangular cartilage graft and the common complications noted were ala
      deformity and tip anaesthesia in 7.6% patients respectively. 

PMID- 24078884
TI  - Bidirectional microglia-neuron communication in the healthy brain.
AB  - Unlike other resident neural cells that are of neuroectodermal origin, microglia
      are resident neural cells of mesodermal origin. Traditionally recognized for
      their immune functions during disease, new roles are being attributed to these
      cells in the development and maintenance of the central nervous system (CNS)
      including specific communication with neurons. In this review, we highlight some
      of the recent findings on the bidirectional interaction between neurons and
      microglia. We discuss these interactions along two lines. First, we review data
      that suggest that microglial activity is modulated by neuronal signals, focusing
      on evidence that (i) neurons are capable of regulating microglial activation
      state and influence basal microglial activities; (ii) classic neurotransmitters
      affect microglial behavior; (iii) chemotactic signals attract microglia during
      acute neuronal injury. Next, we discuss some of the recent data on how microglia
      signal to neurons. Signaling mechanisms include (i) direct physical contact of
      microglial processes with neuronal elements; (ii) microglial regulation of
      neuronal synapse and circuit by fractalkine, complement, and DAP12 signaling. In
      addition, we discuss the use of microglial depletion strategies in studying the
      role of microglia in neuronal development and synaptic physiology. Deciphering
      the mechanisms of bidirectional microglial-neuronal communication provides novel
      insights in understanding microglial function in both the healthy and diseased
      brain. 

PMID- 24078886
TI  - Efficacy of the Radiotherapy on Darier's Disease: An Indirect Evidence.
AB  - Darier's disease (DD) is an autosomal dominant dermatosis characterized by
      hyperkeratotic papules that are mainly located in the seborrheic areas and
      pushups, handheld wells, and nails. The disease often appears at a young age,
      typically by the third decade, with no sex predilection. There is currently no
      standard therapy and there are usually topical palliative therapies. We present
      the case of an affected 42-year-old woman treated with radiation therapy for
      early breast cancer. Before the radiotherapy, the patient showed hyperkeratotic,
      brownish papules extending in a linear pattern for the neck to the abdomen,
      especially on both breasts and inframammary area. During the radiation, she
      developed grade 1 to 2 dermatitis in the irradiated area. At a followup of 6
      months, the patient has no skin lesions in the irradiated zone. This report
      suggests that the radiotherapy is not contraindicated and may indeed be effective
      in local control of skin lesions in DD. 

PMID- 24078885
TI  - Presynaptic glycine receptors increase GABAergic neurotransmission in rat
      periaqueductal gray neurons.
AB  - The periaqueductal gray (PAG) is involved in the central regulation of
      nociceptive transmission by affecting the descending inhibitory pathway. In the
      present study, we have addressed the functional role of presynaptic glycine
      receptors in spontaneous glutamatergic transmission. Spontaneous EPSCs (sEPSCs)
      were recorded in mechanically dissociated rat PAG neurons using a conventional
      whole-cell patch recording technique under voltage-clamp conditions. The
      application of glycine (100 uM) significantly increased the frequency of sEPSCs,
      without affecting the amplitude of sEPSCs. The glycine-induced increase in sEPSC
      frequency was blocked by 1 uM strychnine, a specific glycine receptor antagonist.
      The results suggest that glycine acts on presynaptic glycine receptors to
      increase the probability of glutamate release from excitatory nerve terminals.
      The glycine-induced increase in sEPSC frequency completely disappeared either in
      the presence of tetrodotoxin or Cd(2+), voltage-gated Na(+), or Ca(2+) channel
      blockers, suggesting that the activation of presynaptic glycine receptors might
      depolarize excitatory nerve terminals. The present results suggest that
      presynaptic glycine receptors can regulate the excitability of PAG neurons by
      enhancing glutamatergic transmission and therefore play an important role in the
      regulation of various physiological functions mediated by the PAG.

PMID- 24078887
TI  - Archaeal signal transduction: impact of protein phosphatase deletions on cell
      size, motility, and energy metabolism in Sulfolobus acidocaldarius.
AB  - In this study, the in vitro and in vivo functions of the only two identified
      protein phosphatases, Saci-PTP and Saci-PP2A, in the crenarchaeal model organism
      Sulfolobus acidocaldarius were investigated. Biochemical characterization
      revealed that Saci-PTP is a dual-specific phosphatase (against pSer/pThr and
      pTyr), whereas Saci-PP2A exhibited specific pSer/pThr activity and inhibition by
      okadaic acid. Deletion of saci_pp2a resulted in pronounced alterations in growth,
      cell shape and cell size, which could be partially complemented. Transcriptome
      analysis of the three strains (Deltasaci_ptp, Deltasaci_pp2a and the MW001
      parental strain) revealed 155 genes that were differentially expressed in the
      deletion mutants, and showed significant changes in expression of genes encoding
      the archaella (archaeal motility structure), components of the respiratory chain
      and transcriptional regulators. Phosphoproteome studies revealed 801 unique
      phosphoproteins in total, with an increase in identified phosphopeptides in the
      deletion mutants. Proteins from most functional categories were affected by
      phosphorylation, including components of the motility system, the respiratory
      chain, and regulatory proteins. In the saci_pp2a deletion mutant the up
      regulation at the transcript level, as well as the observed phosphorylation
      pattern, resembled starvation stress responses. Hypermotility was also observed
      in the saci_pp2a deletion mutant. The results highlight the importance of protein
      phosphorylation in regulating essential cellular processes in the crenarchaeon S.
      acidocaldarius. 

PMID- 24078889
TI  - Indigenous Infection with Francisella tularensis holarctica in The Netherlands.
AB  - We report here the first case of indigenous tularemia detected in The
      Netherlands, a nonendemic country, since 1953. Whole genome DNA sequence analysis
      assigned the isolate BD11-00177 to the genomic group B.FTNF002-00, which
      previously has been exclusively reported from Spain, France, Italy, Switzerland,
      and Germany. The patient had not been abroad for years, which implies that this
      is an indigenous infection. The current case might predict an upcoming
      distribution of Francisella tularensis holarctica genomic group B.FTNF002-00 in
      Europe. 

PMID- 24078888
TI  - Comprehensive cell-specific protein analysis in early and late pollen development
      from diploid microsporocytes to pollen tube growth.
AB  - Pollen development in angiosperms is one of the most important processes
      controlling plant reproduction and thus productivity. At the same time, pollen
      development is highly sensitive to environmental fluctuations, including
      temperature, drought, and nutrition. Therefore, pollen biology is a major focus
      in applied studies and breeding approaches for improving plant productivity in a
      globally changing climate. The most accessible developmental stages of pollen are
      the mature pollen and the pollen tubes, and these are thus most frequently
      analyzed. To reveal a complete quantitative proteome map, we additionally
      addressed the very early stages, analyzing eight stages of tobacco pollen
      development: diploid microsporocytes, meiosis, tetrads, microspores, polarized
      microspores, bipolar pollen, desiccated pollen, and pollen tubes. A protocol for
      the isolation of the early stages was established. Proteins were extracted and
      analyzed by means of a new gel LC-MS fractionation protocol. In total, 3817
      protein groups were identified. Quantitative analysis was performed based on
      peptide count. Exceedingly stage-specific differential protein regulation was
      observed during the conversion from the sporophytic to the gametophytic proteome.
      A map of highly specialized functionality for the different stages could be
      revealed from the metabolic activity and pronounced differentiation of
      proteasomal and ribosomal protein complex composition up to protective mechanisms
      such as high levels of heat shock proteins in the very early stages of
      development. 

PMID- 24078890
TI  - Use of an intubating stylet as a guide to complete uterine curettage complicated
      by uterine perforation.
AB  - Completion of uterine curettage may be challenging following uterine perforation
      even under sonographic and laparoscopic monitoring. This report illustrates the
      use of a flexible intubating stylet as a guide to place the suction curette into
      the uterine cavity when sonography and laparoscopy alone are not successful. Use
      of a malleable instrument such as an intubating stylet as a guide should be
      considered an option when insertion of the suction curette into the uterine
      cavity is complicated by anatomic variation and uterine perforation. 

PMID- 24078891
TI  - Cutaneous epithelioid clear cells angiosarcoma in a young woman with congenital
      lymphedema.
AB  - Angiosarcomas are rare aggressive neoplasms that can occur secondary to chronic
      lymphedema (Stewart-Treves syndrome). Although secondary angiosarcomas are
      commonly described after-mastectomy and/or after-radiotherapy, few cases have
      been reported in association with chronic lymphedema of congenital origin. We
      report the clinical, pathological, and cytogenetic findings in a case of
      cutaneous epithelioid clear cells angiosarcoma that occurred in a 21-year-old
      woman with hemibody congenital lymphedema. Surgical biopsies of the tumor mass
      revealed diffuse epithelioid proliferation of clear atypical cells, for which
      immunophenotyping highlighted the vascular differentiation. Despite en bloc
      resection of the tumor, the patient died of metastatic disease three months after
      diagnosis. This case illustrates the clinical and pathology characteristics of
      angiosarcoma that is a rare entity secondary to chronic lymphedema. It is the
      first reported case for which the c-MYC amplification status was assessed. The
      diagnostic value of this amplification should be further evaluated in this
      specific context. 

PMID- 24078892
TI  - Delayed Onset and Prolonged ECT-Related Delirium.
AB  - Electroconvulsive therapy (ECT) is effective in the treatment of depression.
      Delayed post-ECT delirium is rare but can occur in a small subset of patients
      with risk factors and in most cases resolves with the use of psychotropic
      medications. We report a unique presentation of a patient who developed a delayed
      post-ECT delirium with fecal incontinence that commenced 24 hours after the
      administration of ECT. The condition resolved spontaneously after 48 hours
      without the use of psychotropic medications. 

PMID- 24078893
TI  - Successful treatment of bleeding gastric varices with splenectomy in a patient
      with splenic, portal, and mesenteric thromboses.
AB  - A 59-year-old female with a history of multiple splanchnic and portal thromboses
      treated with warfarin underwent an esophagogastroduodenoscopy for cancer
      screening, and a polypoid mass was biopsied. One week later, she was admitted
      with upper gastrointestinal hemorrhage. Her therapeutic coagulopathy was reversed
      with fresh frozen plasma, and she was transfused with packed red blood cells. An
      esophagogastroduodenoscopy demonstrated an erosion of a gastric varix without
      evidence of recent bleeding. Conservative measures failed, and she continued to
      bleed during her stay. She was not considered a candidate for a shunt procedure;
      therefore, a splenectomy was performed. Postoperative esophagogastroduodenoscopy
      demonstrated near complete resolution of gastric varices. One year after
      discharge on warfarin, there has been no recurrence of hemorrhage. Gastric
      varices often arise from either portal hypertension or splenic vein thrombosis.
      Treatment of gastric variceal hemorrhage can be challenging. Transjugular
      intrahepatic portosystemic shunt is often effective for emergency control in
      varices secondary to portal hypertension. Splenectomy is the treatment for
      varices that arise from splenic vein thrombosis. However, treatment of gastric
      variceal hemorrhage in the context of multiple splanchnic and portal vein
      thromboses is more complicated. We report splenectomy as a successful treatment
      of gastric varices in a patient with multiple extrahepatic thromboses. 

PMID- 24078894
TI  - Intraperitoneal urinary bladder perforation observed in a patient with an
      indwelling urethral catheter.
AB  - This report describes a rare case of an 86-year-old man with an indwelling
      urethral catheter who developed severe abdominal pain and was diagnosed with
      intraperitoneal urinary bladder perforation. A home-visiting nurse suspected
      catheter obstruction and performed a catheter exchange. However, bladder
      irrigation could not subsequently be performed. Computed tomography of the
      abdomen and pelvis after transurethral perfusion of contrast medium demonstrated
      extravasation of the contrast material into the peritoneal cavity. Furthermore,
      the Foley catheter balloon was positioned in the peritoneal cavity through the
      bladder. The patient was diagnosed with peritonitis due to spontaneous
      intraperitoneal perforation of the urinary bladder, and exploratory laparotomy
      was performed. During exploration, a perforated tear at the top of the bladder
      was discovered where the Foley catheter had penetrated the bladder. The Foley
      catheter balloon was floating freely in the peritoneal cavity. There was no
      evidence of pathologic lesions, such as cancer or inflammatory mass at the site
      of the injured peritoneum. Successful closure of the damaged peritoneum and
      bladder was performed. Since the proportion of elderly individuals continues to
      increase in the general Japanese population, the incidence of the chronic Foley
      catheterization is expected to increase. Therefore, clinicians should be aware of
      this potential complication. 

PMID- 24078895
TI  - beta -Lactamase-Producing Multidrug-Resistant Bacterial Pathogens from Tracheal
      Aspirates of Intensive Care Unit Patients at National Institute of Neurological
      and Allied Sciences, Nepal.
AB  - The widespread use of tracheal intubation and mechanical ventilation to support
      the critically ill patients increases the risk of development of
      tracheobronchitis and bronchopneumonia. This cross-sectional study was conducted
      with an aim to isolate and identify bacterial pathogens from tracheal aspirates
      producing extended-spectrum beta -lactamase (ESBL), AmpC beta -lactamase, and
      metallo- beta -lactamase (MBL) from August 2011 to April 2012 at National
      Institute of Neurological and Allied Sciences (NINAS), Kathmandu, Nepal. ESBL was
      detected by combined disk assay using cefotaxime and cefotaxime with clavulanate,
      AmpC beta -lactamase by inhibitor-based method using cefoxitin and phenylboronic
      acid, and MBL by Imipenem-EDTA combined disk method. 167 bacterial strains were
      isolated from 187 samples and majority of them were Acinetobacter spp. followed
      by Klebsiella pneumoniae with 32.9% and 25.1%, respectively. 68.8% of isolates
      were multidrug resistant (MDR) and Acinetobacter spp. constituted 85.4%. ESBL,
      AmpC beta -lactamase, and MBL were detected in 35 (25%), 51 (37.2%), and 11
      (36.7%) isolates, respectively. Pseudomonas spp. (42.8%) were the predominant
      ESBL producer while Acinetobacter spp. were the major AmpC beta -lactamase
      producer (43.1%) and MBL producer (54.5%). 

PMID- 24078896
TI  - Robust Multi-Task Feature Learning.
AB  - Multi-task learning (MTL) aims to improve the performance of multiple related
      tasks by exploiting the intrinsic relationships among them. Recently, multi-task
      feature learning algorithms have received increasing attention and they have been
      successfully applied to many applications involving high-dimensional data.
      However, they assume that all tasks share a common set of features, which is too
      restrictive and may not hold in real-world applications, since outlier tasks
      often exist. In this paper, we propose a Robust MultiTask Feature Learning
      algorithm (rMTFL) which simultaneously captures a common set of features among
      relevant tasks and identifies outlier tasks. Specifically, we decompose the
      weight (model) matrix for all tasks into two components. We impose the well-known
      group Lasso penalty on row groups of the first component for capturing the shared
      features among relevant tasks. To simultaneously identify the outlier tasks, we
      impose the same group Lasso penalty but on column groups of the second component.
      We propose to employ the accelerated gradient descent to efficiently solve the
      optimization problem in rMTFL, and show that the proposed algorithm is scalable
      to large-size problems. In addition, we provide a detailed theoretical analysis
      on the proposed rMTFL formulation. Specifically, we present a theoretical bound
      to measure how well our proposed rMTFL approximates the true evaluation, and
      provide bounds to measure the error between the estimated weights of rMTFL and
      the underlying true weights. Moreover, by assuming that the underlying true
      weights are above the noise level, we present a sound theoretical result to show
      how to obtain the underlying true shared features and outlier tasks (sparsity
      patterns). Empirical studies on both synthetic and real-world data demonstrate
      that our proposed rMTFL is capable of simultaneously capturing shared features
      among tasks and identifying outlier tasks.

PMID- 24078897
TI  - A qualitative study to inform the development of a video game for adolescent HIV
      prevention.
AB  - PURPOSE: To inform the development of an interactive video game focused on
      behavior change to reduce risk and promote HIV prevention in young minority
      adolescents. METHODS: We used qualitative methods guided by community-partnered
      research principles to conduct and analyze 16 individual interviews and six focus
      groups with 10-15 year old boys and girls (36 unique participants) at a
      neighborhood-based non-profit organization serving youth from low-resource
      neighborhoods. RESULTS: We identified three recurring themes. Adolescents report
      protective factors and facilitators to engaging in risk behaviors including: 1)
      their personal ability to balance the tension between individuation and group
      membership; 2) the presence of stable mentor figures in their life; and 3) the
      neighborhood in which they live. CONCLUSIONS: By conducting a qualitative study
      guided by community-partnered research principles, we identified themes from our
      target audience that could be translated into a video game-based intervention,
      including the storyline and character development. These methods may increase the
      intervention's efficacy at promoting HIV prevention by making them more tailored
      and relevant to a specific population.

PMID- 24078898
TI  - Translating Drugs From Animals to Humans: Do We Need to Prove Efficacy?

PMID- 24078899
TI  - Non-Insertive Acupuncture and Neonatal Abstinence Syndrome: A Case Series from an
      Inner City Safety Net Hospital.
AB  - OBJECTIVE: We report on the safety of non-insertive acupuncture (NIA) in 54
      newborns diagnosed with Neonatal Abstinence Syndrome (NAS) in a busy inner city
      hospital. METHODS: For this case series, a retrospective chart review was
      conducted. Data on participant demographics, number of NIA treatments, provider
      referrals, and outcomes of interest (sleeping, feeding, and adverse events) were
      collected. RESULTS: Of the 54 newborns receiving NIA, 86% were non-Hispanic
      White; 87% were on Medicaid, and gestational age ranged from 33.2 to 42.1 weeks.
      Out of 54 chart reviews, a total of 92 NIA sessions were documented ranging from
      1 to 6 sessions per infant. Of the total number of treatments (n = 92), 73% were
      requested by a physician. Chart reviews reported restless infants calmed down
      during NIA, babies slept through or fell asleep immediately following NIA, and
      better feeding was noted following NIA. There were no adverse events noted in the
      medical records. CONCLUSIONS: This retrospective chart review shows potential for
      the use of NIA as an adjunctive treatment in newborns with NAS symptoms during
      hospitalization. More research is necessary to study whether the incorporation of
      NIA can result in positive outcomes in newborns withdrawing from narcotics.

PMID- 24078901
TI  - Comparing Web-based with Mail Survey Administration of the Consumer Assessment of
      Healthcare Providers and Systems (CAHPS(r)) Clinician and Group Survey.
AB  - CONTEXT: The CAHPS(r) survey instruments are widely used to assess patient
      experiences with care but there is limited information about web-based data
      collection with them. OBJECTIVE: To compare web-based data collection with
      standard mail survey mode of collection of CAHPS(r) Clinician and Group survey
      data. DESIGN SETTING AND PATIENTS: We randomized mode of data collection (web
      versus mail) of the CAHPS(r) Clinician and Group Survey to patients who had
      visited one of six clinics over a four-month period in Minnesota. A total of 410
      patients responded to the web-based survey (14% response rate) and 982 patients
      responded to the mail survey (33% response rate). MAIN OUTCOME MEASURES:
      Responses to CAHPS(r) survey dimensions and individual question responses,
      response rates, and participant characteristics. RESULTS: There were no
      significant differences in CAHPS(r) survey composites and individual question
      responses by mode, except for those addressing access. Those responding via the
      web reported less positive experiences with access to an appointment for urgent
      care as soon as needed, getting an appointment for routine care as soon as
      needed, getting answers to medical questions as soon as needed, and follow-up on
      test results (t's=-3.64, -7.15, -2.58, -2.23; p's=0.0003, <0.0001, 0.01, 0.03,
      respectively). Web respondents had more positive experiences about office wait
      time for the most recent visit (t = 2.32, p=0.021). Those who participated in the
      study tended to be older than those that did not (lambda2=247.51, df=8, p<0.0001
      for mail; lambda2= 4.56, df=8, p<0.0001 for the web). Females were significantly
      more likely than males to respond to the survey overall (24% vs. 18%,
      lambda2=6.45, 1 df, p=0.011) and relatively more likely than males to respond to
      web (15% vs. 13%, lambda2=1.32, 1 df, p=0.25) than mail (34% vs. 30%,
      lambda2=5.42, 1 df, p=0.02). Mail respondents were more likely than web
      respondents to be male (28% versus 18%, lambda2=16.27, 1 df, p<0.0001) and older
      (27% of the mail respondents and 19% of the web respondents were 65 or older,
      lambda2=10.88, 1 df, p=0.001). Costs of web-based surveys were less than mailed
      surveys and were returned more quickly than mailed surveys. The correlations
      between reports and ratings of clinicians and clinics by mode were unreliable
      because of the relatively small number of web responses. CONCLUSION: Web-based
      surveys yielded comparable results to mail (except for questions addressing
      access) more quickly at lower costs. The low response rates in this study are a
      concern although this was not intended as a test of increasing response rates.
      Strategies to increase response rates will be a key element of web-based data
      collection. The differences in costs will be an incentive for organizations to
      continue to pursue web-based surveying. Further studies are needed to evaluate
      the generalizability of the results of this one.

PMID- 24078900
TI  - In vivo dynamics of innate immune sentinels in the CNS.
AB  - The innate immune system is comprised of cellular sentinels that often serve as
      the first responders to injury and invading pathogens. Our basic understanding of
      innate immunity is derived from research conducted in peripheral lymphoid
      tissues. However, it is now recognized that most non-lymphoid tissues throughout
      the body are equipped with specialized innate immune cells that are uniquely
      adapted to the niches in which they reside. The central nervous system (CNS) is a
      particularly interesting compartment because it contains a population of post
      mitotic cells (neurons) that are intolerant of robust, cytopathic inflammatory
      responses observed in many peripheral tissues. Thus, evolutionary adaptations
      have fitted the CNS with a unique array of innate immune sentinels that
      facilitate the development of local inflammatory responses but attempt to do so
      in a manner that preserves the integrity of its post-mitotic residents.
      Interestingly, studies have even suggested that CNS resident innate immune cells
      contribute to the homeostasis of this compartment and promote neural activity. In
      this review we discuss recent advances in our understanding of CNS innate immune
      sentinels and how novel imaging approaches such as intravital two-photon laser
      scanning microscopy (TPLSM) have shed light on these cells during states of
      health and disease. 

PMID- 24078902
TI  - Gene Expression Under the Influence: Transcriptional Profiling of Ethanol in the
      Brain.
AB  - Sensitivity to ethanol intoxication, propensity to drink ethanol and
      vulnerability to develop alcoholism are all influenced by genetic factors.
      Conversely, exposure to ethanol or subsequent withdrawal produce gene expression
      changes, which, in combination with environmental variables, may participate in
      the emergence of compulsive drinking and relapse. The present review offers an
      integrated perspective on brain gene expression profiling in rodent models of
      predisposition to differential ethanol sensitivity or consumption, in rats and
      mice subjected to acute or chronic ethanol exposure, as well as in human
      alcoholics. The functional categories over-represented among differentially
      expressed genes suggest that the transcriptional effects of chronic ethanol
      consumption contribute to the neuroplasticity and neurotoxicity characteristic of
      alcoholism. Importantly, ethanol produces distinct transcriptional changes within
      the different brain regions involved in intoxication, reinforcement and
      addiction. Special emphasis is put on recent profiling studies that have provided
      some insights into the molecular mechanisms potentially mediating genome-wide
      regulation of gene expression by ethanol. In particular, current evidence for a
      role of transcription factors, chromatin remodeling and microRNAs in coordinating
      the expression of large sets of genes in animals predisposed to excessive ethanol
      drinking or exposed to protracted abstinence, as well as in human alcoholics, is
      presented. Finally, studies that have compared ethanol with other drugs of abuse
      have highlighted common gene expression patterns that may play a central role in
      drug addiction. The availability of novel technologies and a focus on mechanistic
      approaches are shaping the future of ethanol transcriptomics.

PMID- 24078904
TI  - Rhizobium pongamiae sp. nov. from root nodules of Pongamia pinnata.
AB  - Pongamia pinnata has an added advantage of N2-fixing ability and tolerance to
      stress conditions as compared with other biodiesel crops. It harbours "rhizobia"
      as an endophytic bacterial community on its root nodules. A gram-negative,
      nonmotile, fast-growing, rod-shaped, bacterial strain VKLR-01(T) was isolated
      from root nodules of Pongamia that grew optimal at 28 degrees C, pH 7.0 in
      presence of 2% NaCl. Isolate VKLR-01 exhibits higher tolerance to the prevailing
      adverse conditions, for example, salt stress, elevated temperatures and
      alkalinity. Strain VKLR-01(T) has the major cellular fatty acid as C(18:1)
      omega7c (65.92%). Strain VKLR-01(T) was found to be a nitrogen fixer using the
      acetylene reduction assay and PCR detection of a nifH gene. On the basis of
      phenotypic, phylogenetic distinctiveness and molecular data (16S rRNA, recA, and
      atpD gene sequences, G + C content, DNA-DNA hybridization etc.), strain VKLR
      01(T) = (MTCC 10513(T) = MSCL 1015(T)) is considered to represent a novel species
      of the genus Rhizobium for which the name Rhizobium pongamiae sp. nov. is
      proposed. Rhizobium pongamiae may possess specific traits that can be transferred
      to other rhizobia through biotechnological tools and can be directly used as
      inoculants for reclamation of wasteland; hence, they are very important from both
      economic and environmental prospects.

PMID- 24078903
TI  - RUNX Family Participates in the Regulation of p53-Dependent DNA Damage Response.
AB  - A proper DNA damage response (DDR), which monitors and maintains the genomic
      integrity, has been considered to be a critical barrier against genetic
      alterations to prevent tumor initiation and progression. The representative tumor
      suppressor p53 plays an important role in the regulation of DNA damage response.
      When cells receive DNA damage, p53 is quickly activated and induces cell cycle
      arrest and/or apoptotic cell death through transactivating its target genes
      implicated in the promotion of cell cycle arrest and/or apoptotic cell death such
      as p21(WAF1) , BAX, and PUMA. Accumulating evidence strongly suggests that DNA
      damage-mediated activation as well as induction of p53 is regulated by
      posttranslational modifications and also by protein-protein interaction. Loss of
      p53 activity confers growth advantage and ensures survival in cancer cells by
      inhibiting apoptotic response required for tumor suppression. RUNX family, which
      is composed of RUNX1, RUNX2, and RUNX3, is a sequence-specific transcription
      factor and is closely involved in a variety of cellular processes including
      development, differentiation, and/or tumorigenesis. In this review, we describe a
      background of p53 and a functional collaboration between p53 and RUNX family in
      response to DNA damage. 

PMID- 24078905
TI  - Uraemic toxins generated in the presence of fullerene C60, carbon-encapsulated
      magnetic nanoparticles, and multiwalled carbon nanotubes.
AB  - Uraemic toxins-creatol and N-methylguanidine-are generated in conversion of
      creatinine in water in the presence of various forms of carbon such as fullerene
      C60, carbon-encapsulated magnetic nanoparticles, and multiwalled carbon nanotubes
      and oxygen. The conversion degree for creatinine was different for fullerene C60,
      CEMNPs, and MWCNTs and was 9% (3.6% creatol, 5.4% N-methylguanidine), 35% (12%
      creatol, 23% N-methylguanidine), and 75% (16% creatol, 59% N-methylguanidine),
      respectively. 

PMID- 24078906
TI  - Secure encapsulation and publication of biological services in the cloud
      computing environment.
AB  - Secure encapsulation and publication for bioinformatics software products based
      on web service are presented, and the basic function of biological information is
      realized in the cloud computing environment. In the encapsulation phase, the
      workflow and function of bioinformatics software are conducted, the encapsulation
      interfaces are designed, and the runtime interaction between users and computers
      is simulated. In the publication phase, the execution and management mechanisms
      and principles of the GRAM components are analyzed. The functions such as remote
      user job submission and job status query are implemented by using the GRAM
      components. The services of bioinformatics software are published to remote
      users. Finally the basic prototype system of the biological cloud is achieved. 

PMID- 24078907
TI  - Wild plant assessment for heavy metal phytoremediation potential along the mafic
      and ultramafic terrain in northern Pakistan.
AB  - This study investigates the wild plant species for their phytoremediation
      potential of macro and trace metals (MTM). For this purpose, soil and wild plant
      species samples were collected along mafic and ultramafic terrain in the Jijal,
      Dubair, and Alpuri areas of Kohistan region, northern Pakistan. These samples
      were analyzed for the concentrations of MTM (Na, K, Ca, Mg, Fe, Mn, Pb, Zn, Cd,
      Cu, Cr, Ni, and Co) using atomic absorption spectrometer (AAS-PEA-700). Soil
      showed significant (P < .001) contamination level, while plants had greater
      variability in metal uptake from the contaminated sites. Plant species such as
      Selaginella jacquemontii, Rumex hastatus, and Plectranthus rugosus showed
      multifold enrichment factor (EF) of Fe, Mn, Cr, Ni, and Co as compared to
      background area. Results revealed that these wild plant species have the ability
      to uptake and accumulate higher metals concentration. Therefore, these plant
      species may be used for phytoremediation of metals contaminated soil. However,
      higher MTM concentrations in the wild plant species could cause environmental
      hazards in the study area, as selected metals (Fe, Mn, Cr, Ni, Co, and Pb) have
      toxicological concerns. 

PMID- 24078908
TI  - Recognition of multiple imbalanced cancer types based on DNA microarray data
      using ensemble classifiers.
AB  - DNA microarray technology can measure the activities of tens of thousands of
      genes simultaneously, which provides an efficient way to diagnose cancer at the
      molecular level. Although this strategy has attracted significant research
      attention, most studies neglect an important problem, namely, that most DNA
      microarray datasets are skewed, which causes traditional learning algorithms to
      produce inaccurate results. Some studies have considered this problem, yet they
      merely focus on binary-class problem. In this paper, we dealt with multiclass
      imbalanced classification problem, as encountered in cancer DNA microarray, by
      using ensemble learning. We utilized one-against-all coding strategy to transform
      multiclass to multiple binary classes, each of them carrying out feature
      subspace, which is an evolving version of random subspace that generates multiple
      diverse training subsets. Next, we introduced one of two different correction
      technologies, namely, decision threshold adjustment or random undersampling, into
      each training subset to alleviate the damage of class imbalance. Specifically,
      support vector machine was used as base classifier, and a novel voting rule
      called counter voting was presented for making a final decision. Experimental
      results on eight skewed multiclass cancer microarray datasets indicate that
      unlike many traditional classification approaches, our methods are insensitive to
      class imbalance. 

PMID- 24078910
TI  - Biomechanics.

PMID- 24078909
TI  - Helical tomotherapy for inoperable breast cancer: a new promising tool.
AB  - BACKGROUND: We investigated the feasibility of helical tomotherapy (HT) for
      inoperable large breast tumors, after failing to achieve adequate treatment
      planning with conformal radiation techniques. MATERIAL AND METHODS: Five
      consecutive patients with locally advanced breast cancer (LABC) were treated by
      preoperative HT. All patients received up-front chemotherapy before HT.
      Irradiated volumes included breast and nodal areas (45-50 Gy) in 4 patients. One
      patient received a simultaneous integrated boost (55 Gy) to gross tumor volume
      (GTV) without lymph node irradiation. Acute toxicity was assessed with Common
      Toxicity Criteria for Adverse Events v.4. Patients were evaluated for surgery at
      the end of treatment. RESULTS: Patients were staged IIB to IIIC (according to the
      AJCC staging system 2010). HT was associated in 4 patients with concomitant
      chemotherapy (5-fluorouracil and vinorelbine). Two patients were scored with
      grade 3 skin toxicity (had not completed HT) and one with grade 3 febrile
      neutropenia. One patient stopped HT with grade 2 skin toxicity. All patients were
      able to undergo mastectomy at a median interval of 43 days (31-52) from HT.
      Pathological partial response was seen in all patients. CONCLUSIONS: HT is
      feasible with acceptable toxicity profiles, potentially increased by
      chemotherapy. These preliminary results prompt us to consider a phase II study.

PMID- 24078911
TI  - Report on influenza A and B viruses: their coinfection in a Saudi leukemia
      patient.
AB  - PURPOSE: Influenza A and B viruses are the leading cause of respiratory
      infections in children worldwide, particularly in developing countries. There is
      a lack of data on coinfection of influenza A and B viruses circulating in Saudi
      Arabia. In this study, we aimed to identify the circulation of influenza viruses
      that contribute to respiratory tract infections in Saudi children. METHODS: We
      collected 80 nasopharyngeal aspirates (NPAs) from hospitalized children with
      acute respiratory illness (ARI) at Riyadh during the period extended from October
      2010 till April 2011. Samples were tested for the common respiratory viruses
      including influenza viruses by RT-PCR. RESULTS: Overall, 6 samples were found
      positive for influenza A and/or B viruses. Among these positive clinical samples,
      only one collected sample from a female one-year-old immunocompromised child with
      leukemia showed a coinfection with influenza A and B viruses. In present study
      coinfection was confirmed by inoculation of the clinical specimen in specific
      pathogenfree embryonating chicken eggs and identification of the virus isolates
      by hemagglutination and one-step RT-PCR. CONCLUSION: This study opens the scene
      for studying the role of influenza virus's coinfection in disease severity and
      virus evolution. Further studies are required to better understand the clinical
      importance of viral coinfection.

PMID- 24078912
TI  - Information content-based gene ontology semantic similarity approaches: toward a
      unified framework theory.
AB  - Several approaches have been proposed for computing term information content (IC)
      and semantic similarity scores within the gene ontology (GO) directed acyclic
      graph (DAG). These approaches contributed to improving protein analyses at the
      functional level. Considering the recent proliferation of these approaches, a
      unified theory in a well-defined mathematical framework is necessary in order to
      provide a theoretical basis for validating these approaches. We review the
      existing IC-based ontological similarity approaches developed in the context of
      biomedical and bioinformatics fields to propose a general framework and unified
      description of all these measures. We have conducted an experimental evaluation
      to assess the impact of IC approaches, different normalization models, and
      correction factors on the performance of a functional similarity metric. Results
      reveal that considering only parents or only children of terms when assessing
      information content or semantic similarity scores negatively impacts the approach
      under consideration. This study produces a unified framework for current and
      future GO semantic similarity measures and provides theoretical basics for
      comparing different approaches. The experimental evaluation of different
      approaches based on different term information content models paves the way
      towards a solution to the issue of scoring a term's specificity in the GO DAG. 

PMID- 24078913
TI  - Time course of improvement of metabolic parameters after a 12 week physical
      exercise programme in patients with type 2 diabetes: the influence of gender in a
      Nigerian population.
AB  - Gender is a major determinant of the outcomes of many health interventions. This
      study documents the order of significant improvements in metabolic parameters of
      patients with type 2 diabetes mellitus (T2DM) having metabolic syndrome within 12
      weeks of physical exercise programmes. Twenty-nine patients, mean age 49.6 +/-
      3.7 years, presenting with high fasting plasma glucose, high triglycerides,
      hypertension, and high waist circumference undertook a thrice weekly aerobic and
      endurance exercise programme in addition to their drugs and diet. Variables were
      assessed at baseline and end of every two weeks for twelve weeks. Compared with
      baseline, significant improvement (P < 0.05) in the metabolic parameters occurred
      in this order for the male participants: fasting glucose (2nd week),
      triglycerides and waist circumference (4th week), and systolic blood pressure
      (12th week). For the female participants, it was fasting glucose (4th week),
      triglycerides (6th week), and waist circumference (10th week). Regardless of the
      gender, fasting glucose was the first to improve significantly, followed by
      triglycerides. Hypertension did not improve significantly at all in the female
      participants as they may require more than twelve weeks of therapeutic exercise
      for any significant improvement in hypertension. 

PMID- 24078915
TI  - Molecular diagnostics.

PMID- 24078914
TI  - Regulatory interactions between androgens, Hoxb5, and TGF beta signaling in
      murine lung development.
AB  - Androgens enhance airway branching but delay alveolar maturation contributing to
      increased respiratory morbidity in prematurely born male infants. Hoxb5 protein
      positively regulates airway branching in developing lung. In other organs,
      androgen regulation intersects with Hox proteins and TGF beta -SMAD signaling,
      but these interactions have not been studied in the lung. We hypothesized that
      androgen alteration of airway branching early in lung development requires Hoxb5
      expression and that these androgen-Hoxb5 interactions occur partially through
      regional changes in TGF beta signaling. To evaluate acute effects of androgen and
      TGF beta on Hoxb5, E11 whole fetal mouse lungs were cultured with
      dihydrotestosterone (DHT) with/without Hoxb5 siRNA or TGF beta inhibitory
      antibody. Chronic in utero DHT exposure was accomplished by exposing pregnant
      mice to DHT (subcutaneous pellet) from E11 to E18. DHT's ability to enhance
      airway branching and alter phosphorylated SMAD2 cellular localization was
      partially dependent on Hoxb5. Hoxb5 inhibition also changed the cellular
      distribution of SMAD7 protein. Chronic in utero DHT increased Hoxb5 and altered
      SMAD7 mesenchymal localization. TGF beta inhibition enhanced airway branching,
      and Hoxb5 protein cellular localization was more diffuse. We conclude that DHT
      controls lung airway development partially through modulation of Hoxb5 protein
      expression and that this level of regulation involves interactions with TGF beta
      signaling. 

PMID- 24078916
TI  - Models of abnormal scarring.
AB  - Keloids and hypertrophic scars are thick, raised dermal scars, caused by
      derailing of the normal scarring process. Extensive research on such abnormal
      scarring has been done; however, these being refractory disorders specific to
      humans, it has been difficult to establish a universal animal model. A wide
      variety of animal models have been used. These include the athymic mouse, rats,
      rabbits, and pigs. Although these models have provided valuable insight into
      abnormal scarring, there is currently still no ideal model. This paper reviews
      the models that have been developed. 

PMID- 24078917
TI  - Predicting drugs side effects based on chemical-chemical interactions and protein
      chemical interactions.
AB  - A drug side effect is an undesirable effect which occurs in addition to the
      intended therapeutic effect of the drug. The unexpected side effects that many
      patients suffer from are the major causes of large-scale drug withdrawal. To
      address the problem, it is highly demanded by pharmaceutical industries to
      develop computational methods for predicting the side effects of drugs. In this
      study, a novel computational method was developed to predict the side effects of
      drug compounds by hybridizing the chemical-chemical and protein-chemical
      interactions. Compared to most of the previous works, our method can rank the
      potential side effects for any query drug according to their predicted level of
      risk. A training dataset and test datasets were constructed from the benchmark
      dataset that contains 835 drug compounds to evaluate the method. By a jackknife
      test on the training dataset, the 1st order prediction accuracy was 86.30%, while
      it was 89.16% on the test dataset. It is expected that the new method may become
      a useful tool for drug design, and that the findings obtained by hybridizing
      various interactions in a network system may provide useful insights for
      conducting in-depth pharmacological research as well, particularly at the level
      of systems biomedicine. 

PMID- 24078918
TI  - Analysis of the magnetic field influence on the rheological properties of healthy
      persons blood.
AB  - The influence of magnetic field on whole blood rheological properties remains a
      weakly known phenomenon. An in vitro analysis of the magnetic field influence on
      the rheological properties of healthy persons blood is presented in this work.
      The study was performed on blood samples taken from 25 healthy nonsmoking persons
      and included comparative analysis of the results of both the standard rotary
      method (flow curve measurement) and the oscillatory method known also as the
      mechanical dynamic analysis, performed before and after exposition of blood
      samples to magnetic field. The principle of the oscillatory technique lies in
      determining the amplitude and phase of the oscillations of the studied sample
      subjected to action of a harmonic force of controlled amplitude and frequency.
      The flow curve measurement involved determining the shear rate dependence of
      blood viscosity. The viscoelastic properties of the blood samples were analyzed
      in terms of complex blood viscosity. All the measurements have been performed by
      means of the Contraves LS40 rheometer. The data obtained from the flow curve
      measurements complemented by hematocrit and plasma viscosity measurements have
      been analyzed using the rheological model of Quemada. No significant changes of
      the studied rheological parameters have been found. 

PMID- 24078919
TI  - A model for provision of ENT health care service at primary and secondary
      hospital level in a developing country.
AB  - ENT problems are the most common reason for a visit to a doctor in both rural and
      urban communities. In many developing countries, there is a lack of ENT
      specialists and overburdened hospital facilities. To date, there is no
      comprehensive study that has evaluated the spectrum of ENT disorders in a rural
      community. METHODS: A prospective study was done for a period of three years to
      profile the cases presenting to the outpatient clinic in a secondary care
      hospital and in the camps conducted in tribal areas in Vellore District of Tamil
      Nadu, India. Trained community volunteers were used to identify ENT conditions
      and refer patients. RESULTS: A total of 2600 patients were evaluated and treated.
      Otological symptoms were the most commonly reported with allergic rhinitis being
      the second most commonly reported. Presbycusis was the most common disability
      reported in the rural community. The other symptoms presented are largely related
      to hygiene and nutrition. CONCLUSION: Using trained community workers to spread
      the message of safe ENT practices, rehabilitation of hearing loss through
      provision of hearing aids, and the evaluation and surgical management by ENT
      specialist helped the rural community to access the service.

PMID- 24078920
TI  - An alternative approach to protein folding.
AB  - A diffusion theory-based, all-physical ab initio protein folding simulation is
      described and applied. The model is based upon the drift and diffusion of protein
      substructures relative to one another in the multiple energy fields present.
      Without templates or statistical inputs, the simulations were run at physiologic
      and ambient temperatures (including pH). Around 100 protein secondary structures
      were surveyed, and twenty tertiary structures were determined. Greater than 70%
      of the secondary core structures with over 80% alpha helices were correctly
      identified on protein ranging from 30 to 200 amino-acid sequence. The drift
      diffusion model predicted tertiary structures with RMSD values in the 3-5
      Angstroms range for proteins ranging 30 to 150 amino acids. These predictions are
      among the best for an all ab initio protein simulation. Simulations could be run
      entirely on a desktop computer in minutes; however, more accurate tertiary
      structures were obtained using molecular dynamic energy relaxation. The drift
      diffusion model generated realistic energy versus time traces. Rapid secondary
      structures followed by a slow compacting towards lower energy tertiary structures
      occurred after an initial incubation period in agreement with observations. 

PMID- 24078921
TI  - The utility of digital linear tomosynthesis imaging of total hip joint
      arthroplasty with suspicion of loosening: a prospective study in 40 patients.
AB  - AIM: The clinical utility of digital linear tomosynthesis in musculoskeletal
      applications has been validated in only a few reports. Technical performance and
      utility in hip prosthesis imaging have been discussed in technical reports, but
      no clinical evaluation has been reported. The purpose of the current study was to
      assess the added clinical utility of digital linear tomosynthesis compared to
      radiography in loosening of total hip joint arthroplasty. MATERIALS AND METHODS:
      In a prospective study, radiography and digital tomosynthesis were performed in
      40 consecutive patients with total hip arthroplasty referred for suspect
      prosthesis loosening. Tomosynthesis images were compared to anterior-posterior
      (AP) and cross-table lateral radiographs regarding demarcation and extent of
      demineralization and osteolysis. Further noted were skeletal fractures, cement
      fractures, fragmentation, and artifacts interfering with the diagnosis. RESULTS:
      Tomosynthesis was superior to radiography with sharper delineation of
      demineralization and osteolysis in the AP projection. A limitation was the
      inability to generate lateral tomosynthesis images, with inferior assessment of
      the area anterior and posterior to the acetabular cup compared to cross-table
      radiographs. Artifacts interfering with diagnosis were found in one hip.
      CONCLUSION: Tomosynthesis improved evaluation of total hip arthroplasty in the AP
      projection but was limited by the lack of lateral projections.

PMID- 24078922
TI  - Antioxidant, antiproliferative, and antiangiogenesis effects of polyphenol-rich
      seaweed (Sargassum muticum).
AB  - In the present study, we evaluated the effect of brown seaweeds Sargassum muticum
      methanolic extract (SMME), against MCF-7 and MDA-MB-231 breast cancer cell lines
      proliferation. This algae extract was also evaluated for reducing activity and
      total polyphenol content. The MTT assay results indicated that the extracts were
      cytotoxic against breast cancer cell lines in a dose-dependent manner, with IC50
      of 22 MUg/ml for MCF-7 and 55 MUg/ml for MDA-MB-231 cell lines. The percentages
      of apoptotic MCF-7-treated cells increased from 13% to 67% by increasing the
      concentration of the SMME. The antiproliferative efficacy of this algal extract
      was positively correlated with the total polyphenol contents, suggesting a causal
      link related to extract content of phenolic acids. Cell cycle analysis showed a
      significant increase in the accumulation of SMME-treated cells at sub-G1 phase,
      indicating the induction of apoptosis by SMME. Further apoptosis induction was
      confirmed by Hoechst 33342 and AO/PI staining. Also SMME implanted in vivo into
      fertilized chicken eggs induced dose-related antiangiogenic activity in the
      chorioallantoic membrane (CAM). Our results imply a new insight on the novel
      function of Sargassum muticum polyphenol-rich seaweed in cancer research by
      induction of apoptosis, antioxidant, and antiangiogenesis effects.

PMID- 24078923
TI  - Exploring the possible role of lysine acetylation on Entamoeba histolytica
      virulence: a focus on the dynamics of the actin cytoskeleton.
AB  - Cytoskeleton remodeling can be regulated, among other mechanisms, by lysine
      acetylation. The role of acetylation on cytoskeletal and other proteins of
      Entamoeba histolytica has been poorly studied. Dynamic rearrangements of the
      actin cytoskeleton are crucial for amebic motility and capping formation,
      processes that may be effective means of evading the host immune response. Here
      we report the possible effect of acetylation on the actin cytoskeleton dynamics
      and in vivo virulence of E. histolytica. Using western blot, immunoprecipitation,
      microscopy assays, and in silico analysis, we show results that strongly suggest
      that the increase in Aspirin-induced cytoplasm proteins acetylation reduced cell
      movement and capping formation, likely as a consequence of alterations in the
      structuration of the actin cytoskeleton. Additionally, intrahepatic inoculation
      of Aspirin-treated trophozoites in hamsters resulted in severe impairment of the
      amebic virulence. Taken together, these results suggest an important role for
      lysine acetylation in amebic invasiveness and virulence. 

PMID- 24078924
TI  - Superoxide-dismutase deficient mutants in common beans (Phaseolus vulgaris L.):
      genetic control, differential expressions of isozymes, and sensitivity to
      arsenic.
AB  - Two common bean (Phaseolus vulgaris L.) mutants, sodPv 1 and sodPv 2, exhibiting
      foliar superoxide dismutase (SOD) activity of only 25% and 40% of their mother
      control (MC) cv. VL 63 were isolated in EMS-mutagenized (0.15%, 8 h) M2 progeny.
      Native-PAGE analysis revealed occurrence of Mn SOD, Fe SOD, Cu/Zn SOD I and Cu/Zn
      SOD II isozymes in MC, while Fe SOD, and Mn SOD were not formed in sodPv 1 and
      sodPv 2 leaves, respectively. In-gel activity of individual isozymes differed
      significantly among the parents. SOD deficiency is inherited as recessive
      mutations, controlled by two different nonallelic loci. Gene expressions using
      qRT PCR confirmed higher expressions of Cu/Zn SOD transcripts in both mutants and
      the absence of Fe SOD in sodPv 1 and Mn SOD in sodPv 2. In 50 MUM arsenic, Cu/Zn
      SODs genes were further upregulated but other isoforms downregulated in the two
      mutants, maintaining SOD activity in its control level. In an F2 double mutants
      of sodPv 1 * sodPv 2, no Fe SOD, and Mn SOD expressions were detectable, while
      both Cu/Zn SODs are down-regulated and arsenic-induced leaf necrosis appeared. In
      contrast to both mutants, ROS-imaging study revealed overaccumulation of both
      superoxides and H2O2 in leaves of double mutant.

PMID- 24078925
TI  - Prevalence of chronic headache in Croatia.
AB  - BACKGROUND: Chronic headache describes the presence of headache for >15 days per
      month on average for >3 months and fulfills the rest of the IHS criteria. The
      prevalence of chronic headache is within the range of 0.5-7.3% worldwide. The aim
      of this study was to determine the 1-year prevalence of chronic headache in adult
      Croatian population. METHODS: The data were collected from a cross-sectional
      survey of an adult population (>18 years of age) sample. Randomly selected
      patients from the general population in four Croatian cities were asked to
      fulfill a self-completed questionnaire. The prevalence of chronic headache was
      calculated in the sample representing 3,383,769 Croatian adults. RESULTS: The
      total sample included 1542 responders among which 616 were with headache. The 1
      year prevalence of chronic headache was 2.4%, and 0.9% of responders declared
      having headache 30 days per month. According to these results, 81,192 adult
      inhabitants in Croatia suffer from chronic headache. CONCLUSIONS: The prevalence
      of chronic headache in Croatia is comparable to other countries worldwide. These
      patients require special attention and should be offered multidisciplinary
      medical support.

PMID- 24078926
TI  - Responses of growth performance and proinflammatory cytokines expression to fish
      oil supplementation in lactation sows' and/or weaned piglets' diets.
AB  - The study was conducted to investigate whether dietary fish oil could influence
      growth of piglets via regulating the expression of proinflammatory cytokines. A
      split-plot experimental design was used with sow diet effect in the main plots
      and differing piglet diet effect in the subplot. The results showed that suckling
      piglets from fish oil fed dams grew rapidly (P < 0.05) than control. It was also
      observed that these piglets had higher ADG, feed intake, and final body weight (P
      < 0.05) during postweaning than those piglets from lard fed dams. Furthermore,
      there was a significant decrease (P < 0.01) in the expression of interleukin 6
      and tumor necrosis factor- alpha in longissimus dorsi muscle. In contrast, there
      was a tendency (P < 0.10) towards lower ADG and higher feed:gain in weaned
      piglets receiving fish oil compared with those receiving lard. Meanwhile, splenic
      proinflammatory cytokines expression was increased (P < 0.01) in piglets
      receiving fish oil during postweaning period. The results suggested that 7% fish
      oil addition to sows' diets alleviated inflammatory response via decreasing the
      proinflammatory cytokines expression in skeletal muscle and accelerated piglet
      growth. However, 7% fish oil addition to weaned piglets' diets might decrease
      piglet growth via increasing splenic proinflammatory cytokines expression.

PMID- 24078927
TI  - Synthesis of a novel thiazolidinedione and evaluation of its modulatory effect on
      IFN- gamma , IL-6, IL-17A, and IL-22 production in PBMCs from rheumatoid
      arthritis patients.
AB  - Rheumatoid arthritis (RA) is an autoimmune disease frequently characterized by
      chronic synovitis of multiple joints. The pathogenesis of RA is complex and
      involves many proinflammatory cytokines as Th17 related ones. PPAR gamma is a
      nuclear receptor activator that represses proinflammatory gene expression. Thus,
      this work aimed to synthetize a new thiazolidinedione (TZD) analogue based on a
      well-known anti-inflammatory and PPAR gamma agonist activity of this ring and
      evaluate its anti-inflammatory activity. After chemical structure confirmation,
      the compound named 5-(5-bromo-2-methoxy-benzylidene)-3-(2-nitro-benzyl)
      thiazolidine-2,4-dione TM17 was submitted to cytokine releasing inhibition and
      PPAR gamma genetic modulation assays. The new compound showed no toxicity on
      human and murine cells, decreasing IL-6 secretion by murine splenocytes and
      reducing IL-17A, IL-22, and IFN- gamma expression in peripheral blood mononuclear
      cells from patients with RA. TM17 was more efficient in modulating the mRNA
      expression of PPAR gamma than its well-used TZD agonist rosiglitazone.
      Surprisingly, TM17 was efficient on IL-17A and IFN- gamma reduction, like the
      positive control methylprednisolone, and presented a better effect on IL-22
      levels. In conclusion, PBMCs obtained from RA patients under TM17 treatment
      present a significant reduction in IL-17A, IL-22, and IFN- gamma levels, but not
      IL-6 when compared with nontreated cells, as well as increase PPAR gamma mRNA
      expression in absence of stimulus addressing it as a promising molecule in RA
      treatment. 

PMID- 24078928
TI  - Insight into biological apatite: physiochemical properties and preparation
      approaches.
AB  - Biological apatite is an inorganic calcium phosphate salt in apatite form and
      nano size with a biological derivation. It is also the main inorganic component
      of biological hard tissues such as bones and teeth of vertebrates. Consequently,
      biological apatite has a wide application in dentistry and orthopedics by using
      as dental fillers and bone substitutes for bone reconstruction and regeneration.
      Given this, it is of great significance to obtain a comprehensive understanding
      of its physiochemical and biological properties. However, upon the previous
      studies, inconsistent and inadequate data of such basic properties as the
      morphology, crystal size, chemical compositions, and solubility of biological
      apatite were reported. This may be ascribed to the differences in the source of
      raw materials that biological apatite are made from, as well as the effect of the
      preparation approaches. Hence, this paper is to provide some insights rather than
      a thorough review of the physiochemical properties as well as the advantages and
      drawbacks of various preparation methods of biological apatite. 

PMID- 24078929
TI  - Preventative and therapeutic probiotic use in allergic skin conditions:
      experimental and clinical findings.
AB  - Probiotics are ingested live microbes that can modify intestinal microbial
      populations in a way that benefits the host. The interest in probiotic
      preventative/therapeutic potential in allergic diseases stemmed from the fact
      that probiotics have been shown to improve intestinal dysbiosis and permeability
      and to reduce inflammatory cytokines in human and murine experimental models.
      Enhanced presence of probiotic bacteria in the intestinal microbiota is found to
      correlate with protection against allergy. Therefore, many studies have been
      recently designed to examine the efficacy of probiotics, but the literature on
      the allergic skin disorders is still very scarce. Here, our objective is to
      summarize and evaluate the available knowledge from randomized or nonrandomized
      controlled trials of probiotic use in allergic skin conditions. Clinical
      improvement especially in IgE-sensitized eczema and experimental models such as
      atopic dermatitis-like lesions (trinitrochlorobenzene and picryl chloride
      sensitizations) and allergic contact dermatitis (dinitrofluorobenzene
      sensitization) has been reported. Although there is a very promising evidence to
      recommend the addition of probiotics into foods, probiotics do not have a proven
      role in the prevention or the therapy of allergic skin disorders. Thus, being
      aware of possible measures, such as probiotics use, to prevent/heal atopic
      diseases is essential for the practicing allergy specialist. 

PMID- 24078930
TI  - Increased production of interleukin-4, interleukin-10, and granulocyte-macrophage
      colony-stimulating factor by type 2 diabetes' mononuclear cells infected with
      dengue virus, but not increased intracellular viral multiplication.
AB  - It has been reported that diabetes mellitus (DM) was an epidemiologically
      identified risk factor for development of dengue hemorrhagic fever (DHF)/severe
      dengue in dengue virus (DENV) affected patients, and T helper 2 (Th2) cytokines
      such as interleukin-4 (IL-4) and IL-10 each plays an important role in the
      immunopathogenesis of DHF in studies involving general population. To better
      understand the relationship between these epidemiological and immunological
      findings, we performed an in vitro study evaluating the sequential immunological
      reactions and viral load in the DENV infected mononuclear cells of adults with
      type 2 DM (T2DM group, n = 33) and normal adults (control group, n = 29). We
      found in the T2DM group significantly higher IL-4 level on the first (P = 0.049)
      and the third (P = 0.022) postinfection days, while higher IL-10 (P = 0.042) and
      granulocyte-macrophage colony-stimulating factor (GM-CSF) (P = 0.009) were
      detected on the third postinfection day. No significant difference in DENV viral
      load between the cultured mononuclear cells from both groups was found on the
      first and third post-infection days. These data immunologically suggest that
      patients with T2DM are at higher risk for development of DHF/severe dengue and
      strengthen the previously epidemiologically identified role of DM being a
      predictive risk factor for progressing into DHF/severe dengue in DENV-affected
      patients. 

PMID- 24078932
TI  - Closure of a percutaneous endoscopic gastrostomy-associated nonhealing
      gastrocutaneous fistula using endoscopic hemoclips.

PMID- 24078933
TI  - Dynamic position change at colonoscopy improves adenoma detection.

PMID- 24078931
TI  - An insight into the "-omics" based engineering of streptomycetes for secondary
      metabolite overproduction.
AB  - Microorganisms produce a range of chemical substances representing a vast
      diversity of fascinating molecular architectures not available in any other
      system. Among them, Streptomyces are frequently used to produce useful enzymes
      and a wide variety of secondary metabolites with potential biological activities.
      Streptomyces are preferred over other microorganisms for producing more than half
      of the clinically useful naturally originating pharmaceuticals. However, these
      compounds are usually produced in very low amounts (or not at all) under typical
      laboratory conditions. Despite the superiority of Streptomyces, they still lack
      well documented genetic information and a large number of in-depth molecular
      biological tools for strain improvement. Previous attempts to produce high
      yielding strains required selection of the genetic material through classical
      mutagenesis for commercial production of secondary metabolites, optimizing
      culture conditions, and random selection. However, a profound effect on the
      strategy for strain development has occurred with the recent advancement of whole
      genome sequencing, systems biology, and genetic engineering. In this review, we
      demonstrate a few of the major issues related to the potential of "-omics"
      technology (genomics, transcriptomics, proteomics, and metabolomics) for
      improving streptomycetes as an intelligent chemical factory for enhancing the
      production of useful bioactive compounds. 

PMID- 24078934
TI  - A simple method to improve adenoma detection rate during colonoscopy: altering
      patient position.
AB  - BACKGROUND: Colonoscopy is currently considered to be the gold standard method
      for detecting and removing adenomatous polyps. However, tandem colonoscopy
      studies reveal a pooled polyp miss rate of 22%. OBJECTIVE: A prospective
      randomized trial was conducted to assess whether alteration of patient position
      during colonoscopy withdrawal increases the adenoma detection rate (ADR). METHOD:
      The study group included 120 patients who presented for elective colonoscopic
      examination. After reaching the cecum, patients were randomly assigned in a 1:1
      ratio to examination in either the left lateral position or other positions (left
      lateral position for the cecum, ascending colon and hepatic flexure; supine for
      transverse colon; and supine and right lateral position for splenic flexure,
      descending and sigmoid colon) first. Examination of the colon was performed
      segment by segment. The size, morphology and location of all polyps were
      recorded. Polyps were removed immediately after examination of a colon segment
      when all positions were completed. ADR and polyp detection rates (PDR) were
      calculated. RESULTS: A total of 102 patients completed the study. Examination in
      the left lateral position revealed 66 polyps in 31 patients (PDR 30.3%) and 42
      adenomas in 24 patients (ADR 23.5%). PDR increased to 43.1% (81 polyps in 44
      patients) and the ADR to 33.3% (53 adenomas in 34 patients) after the colon was
      examined in the additional positions (P<0.001 and P=0.002, respectively). The
      increase in the number of adenomas detected was statistically significant in the
      transverse and sigmoid colon. The addition of position changes led to a 9.8%
      increase in the ADR in the transverse colon, splenic flexure, and descending and
      sigmoid colon. The frequency of surveillance interval was shortened in nine
      (8.8%) patients after examination of the colon in dynamic positions. CONCLUSION:
      Alteration of patient position during colonoscopy withdrawal is a simple and
      effective method to improve ADR.

PMID- 24078935
TI  - Biliary drainage method and temporal trends in patients admitted with
      cholangitis: a national audit.
AB  - BACKGROUND: In patients presenting with ascending cholangitis, better outcomes
      are reported in those undergoing endoscopic retrograde cholangiopancreatography
      (ERCP) compared with surgical drainage. OBJECTIVE: To identify factors associated
      with the type of intervention, and to examine temporal trends in the treatment of
      ascending cholangitis. METHODS: Data were extracted from the Nationwide Inpatient
      Sample. Patients >=18 years of age with a diagnosis of cholangitis between 1998
      and 2009 were selected. Temporal trends were assessed using Poisson regression
      models. Multivariable models were fitted to predict the likelihood of a patient
      undergoing ERCP, percutaneous or surgical drainage, or no drainage. RESULTS: A
      weighted estimate of 248,942 patients admitted for cholangitis was identified.
      Overall, 131,052 patients were treated with ERCP (52.6%), 10,486 with
      percutaneous drainage (4.2%) and 12,460 with surgical drainage (5.0%); 43.0% did
      not receive drainage during the admission. Temporal trends between 1998 and 2009
      showed a decline in surgical and percutaneous drainage, and a rise in ERCP. In
      multivariable analyses adjusted for clustering, ERCP and percutaneous drainage
      were more often performed in institutions with a high volume of admissions for
      cholangitis, those with a greater bed number and hospitals located in urban
      areas. CONCLUSION: Over the past decade, the use of surgical and percutaneous
      drainage has decreased while that of ERCP has risen. Patients treated at
      institutions with a low volume of admissions for cholangitis, small bed number
      and in rural areas were less likely to undergo ERCP or percutaneous drainage.

PMID- 24078936
TI  - General anesthetic versus light sedation: effect on pediatric endoscopy wait
      times.
AB  - BACKGROUND: Wait times are an important measure of health care system
      effectiveness. There are no studies describing wait times in pediatric
      gastroenterology for either outpatient visits or endoscopy. Pediatric endoscopy
      is performed under light sedation or general anesthesia. The latter is
      hypothesized to be associated with a longer wait time due to practical limits on
      access to anesthesia in the Canadian health care system. OBJECTIVE: To identify
      wait time differences according to sedation type and measure adverse clinical
      outcomes that may arise from increased wait time to endoscopy in pediatric
      patients. METHODS: The present study was a retrospective review of medical charts
      of all patients <18 years of age who had been assessed in the pediatric
      gastroenterology clinic and were scheduled for an elective outpatient endoscopic
      procedure at McMaster Children's Hospital (Hamilton, Ontario) between January
      2006 and December 2007. The primary outcome measure was time between clinic visit
      and date of endoscopy. Secondary outcome measures included other defined waiting
      periods and complications while waiting, such as emergency room visits and
      hospital admissions. RESULTS: The median wait time to procedure was 64 days for
      general anesthesia patients and 22 days for patients who underwent light sedation
      (P<0.0001). There was no significant difference between the two groups with
      regard to the number of emergency room visits or hospital admissions, both pre-
      and postendoscopy. CONCLUSIONS: Due to the lack of pediatric anesthetic
      resources, patients who were administered general anesthesia experienced a longer
      wait time for endoscopy compared with patients who underwent light sedation. This
      did not result in adverse clinical outcomes in this population.

PMID- 24078937
TI  - Immunoglobulin G4-related pancreatic and biliary diseases.
AB  - BACKGROUND: Autoimmune pancreatitis and autoimmune cholangitis are new clinical
      entities that are now recognized as the pancreatico-biliary manifestations of
      immunoglobulin (Ig) G4-related disease. OBJECTIVE: To summarize important
      clinical aspects of IgG4-related pancreatic and biliary diseases, and to review
      the role of IgG4 in the diagnosis of autoimmune pancreatitis (AIP) and autoimmune
      cholangitis (AIC). METHODS: A narrative review was performed using the PubMed
      database and the following keywords: "IgG4", "IgG4 related disease", "autoimmune
      pancreatitis", "sclerosing cholangitis" and "autoimmune cholangitis". A total of
      955 articles were retrieved; of these, 381 contained relevant data regarding the
      IgG4 molecule, pathogenesis of IgG-related diseases, and diagnosis, management
      and long-term follow-up for patients with AIP and AIC. Of these 381 articles, 66
      of the most pertinent were selected. RESULTS: The selected studies demonstrated
      the increasing clinical importance of both AIP and AIC, which can mimic
      pancreatic cancer and cholangiocarcinoma, respectively. IgG4 titration in tissue
      or blood cannot be used alone to diagnose all IgG4-related diseases; however, it
      is often a useful adjunct to clinical, radiological and histological features.
      AIP and AIC respond to steroids; however, relapse is common and long-term
      maintenance treatment often required. CONCLUSIONS: A review of the diagnosis and
      management of both AIC and AIP is timely and pertinent to clinical practice
      because the amount of information regarding these conditions has increased
      substantially in the past few years, resulting in significant impact on the
      clinical management of affected patients.

PMID- 24078939
TI  - We need better care coordination for polytraumatized patients.

PMID- 24078940
TI  - 5 points on transtibial anterior cruciate ligament reconstruction.

PMID- 24078938
TI  - Challenges in the diagnosis and management of autoimmune hepatitis.
AB  - BACKGROUND: Autoimmune hepatitis has diverse clinical phenotypes and outcomes
      that challenge current diagnostic criteria and management algorithms. OBJECTIVES:
      To highlight the major difficulties in diagnosis and management, describe the
      efforts to ease them and encourage further progress in problem solving. METHODS:
      The MEDLINE database was reviewed for published experiences from 1984 to 2013.
      RESULTS: Acute or acute severe (fulminant) hepatitis, asymptomatic mild disease,
      and histological findings of centrilobular necrosis or bile duct injury can
      confound diagnosis and treatment. Continuation of conventional therapy until
      normal liver test results and liver tissue reduces the frequency of relapse, but
      does not prevent its occurrence. Problematic patients can be identified using
      mathematical models, clinical phenotype, serological markers and the speed of
      improvement after treatment; however, their recognition and treatment are
      inconsistent. Mycophenolate mofetil can rescue patients with azathioprine
      intolerance but is less effective for refractory disease. Budesonide in
      combination with azathioprine can be used frontline, but is effective primarily
      in noncirrhotic, uncomplicated disease. Molecular and cellular interventions are
      feasible but largely unevaluated. DISCUSSION: Resolution of the current
      challenges requires revision of diagnostic criteria, characterization of
      biological markers that reflect pathogenic pathways, development of dynamic
      indexes based on changes in disease behaviour, and introduction of new
      pharmacological, molecular and cellular interventions that have undergone
      rigorous evaluation. CONCLUSION: These challenges reflect important remediable
      deficiencies in current management.

PMID- 24078941
TI  - Disk degeneration in lumbar spine precedes osteoarthritic changes in hip.
AB  - It is not clear whether spinal degeneration leads to hip arthritis, or hip
      arthritis leads to spinal degeneration. We conducted a study to determine which
      degenerative process precedes the other. We examined 340 cadaveric human
      specimens from the Hamann-Todd Osteological Collection (Cleveland, Ohio). Lumbar
      endplate degeneration was graded on a scale of 0 to 4, and hip degeneration on a
      scale of 0 to 3. Linear regression was used to analyze the relationship between
      hip osteoarthritis (OA) and lumbar degenerative disk disease (DDD). Exact tests
      were used to identify differences in each age group. Hip OA was significantly
      associated with endplate degeneration at the L1, L3, and L5 levels (P<.02). Of
      the specimens younger than 29 years, 35% had evidence of DDD in at least 1 lumbar
      level, and 17% of hip OA changes. At 70 years, 100% of the specimens had evidence
      of DDD and 50% of hip OA changes. There was a significant association between
      lumbar DDD and hip OA changes (P<.05). Early lumbar DDD was twice as common as
      hip OA changes in the early 20s age range. These findings suggest that lumbar
      degeneration precedes hip degeneration and may be a causative factor for hip OA. 

PMID- 24078942
TI  - Investigation of the asporin gene polymorphism as a risk factor for knee
      osteoarthritis in Iran.
AB  - Osteoarthritis (OA) is a degenerative disease of the joints characterized by
      degradation of the hyaline articular cartilage and remodeling of the subchondral
      bone with sclerosis. The asporin (ASPN) gene encodes a cartilage extracellular
      protein belonging to the small leucine-rich proteoglycan family. Polymorphisms in
      the aspartic acid (D) repeat region in the second exon of this gene, which
      consist of GAT repeats, are associated with OA susceptibility. The D14 allele,
      which contains 14 D-repeats, is associated with increased OA susceptibility in
      the Japanese and the Han Chinese but is not an important factor in OA etiology
      among Caucasians, though the D15 allele is a risk allele for the Greek
      population. To examine the possibility of this controversial association, we
      explored the effect of ASPN on Iranians with knee OA. The D-repeat polymorphism
      was genotyped in 100 knee OA patients and 100 controls, and the allelic
      association of the D-repeat was examined. Our data suggest that the D15 allele
      could be considered a risk allele significant only for women (P = .045, odds
      ratio = 1.73, 95% confidence interval [CI] = 1.01-2.94) in the Iranian
      population. This association is in part similar to that found for the Greek
      population. 

PMID- 24078943
TI  - Clinical measurement of patellar tendon: accuracy and relationship to surgical
      tendon dimensions.
AB  - Patellar tendon width and length are commonly used for preoperative planning for
      anterior cruciate ligament reconstruction (ACLR). In the study reported here, we
      assessed the accuracy of preoperative measurements made by palpation through the
      skin, and correlated these measurements with the actual dimensions of the tendons
      at surgery. Before making incisions in 53 patients undergoing ACLR with patellar
      tendon autograft, we measured patellar tendon length with the knee in full
      extension and in 90 degrees  of flexion, and tendon width with the knee in 90
      degrees  of flexion. The tendon was then exposed, and its width was measured with
      the knee in 90 degrees  of flexion. The length of the central third of the tendon
      was measured after the graft was prepared. Mean patellar tendon length and width
      with the knee in 90 degrees  of flexion were 39 mm and 32 mm, respectively. No
      clinical difference was found between the estimated pre-incision and surgical
      widths. However, the estimated pre-incision length with the knee in full
      extension and in 90 degrees  of flexion was significantly shorter than the
      surgical length. Skin measurements can be used to accurately determine patellar
      tendon width before surgery, but measurements of length are not as reliable. 

PMID- 24078944
TI  - Reliability and accuracy of templating humeral and ulnar components for total
      elbow arthroplasty.
AB  - We conducted a study to examine intraobserver reliability, interobserver
      reliability, and accuracy of preoperative templating in approximating humeral and
      ulnar component sizes in total elbow arthroplasty (TEA). Twenty-two patients
      underwent cemented TEA with 1 of 2 commonly used implants. Four independent
      reviewers performed templating in 2 separate sessions spaced a minimum of 2 weeks
      apart. Reviewers were blinded to patient information and used appropriately
      magnified templates provided by the implant manufacturer. Preoperative and
      postoperative films were assessed for humeral and ulnar stem width and length.
      For both implants combined, there was substantial (kappa > 0.7) intraobserver
      reliability for humeral width, humeral length, and ulnar length. Interobserver
      reliability was fair for humeral width (kappa = 0.28), substantial for humeral
      length (kappa = 0.64), and moderate for both ulnar width (kappa = 0.44) and ulnar
      length (kappa = 0.49). Preoperative templating accurately predicted exact stem
      size 72.7% of the time and within 1 size variation 96.9% of the time. Attending
      surgeons were slightly more accurate than fellows (75.5% vs 71.5%) in predicting
      stem sizes. Preoperative templating is moderately reliable and largely accurate
      in planning TEA. 

PMID- 24078945
TI  - Effects of bilateral distal femoral stress in a patient on long-term pamidronate.
AB  - Recent studies have shown an association between long-term bisphosphonate therapy
      and low-energy subtrochanteric femoral fractures. These fractures have the
      unusual characteristics of occurring after a period of prodromal symptoms such as
      local pain, stress reaction, and low-energy transverse or oblique fractures in
      the subtrochanteric area of the femur. In this article, we present the case of a
      62-year-old patient who was on pamidronate when she fell and sustained a femoral
      fracture resulting from bilateral stress phenomena in the distal third of the
      femoral shaft. Before the fracture, she had osteoporosis (confirmed with dual
      energy x-ray absorptiometry) and prodromal symptoms in the right thigh. She also
      had left thigh pain radiating to the left knee, which was attributed to lower
      thigh pain from a prior diagnosis of osteoarthritis (OA) in the left knee. The
      femoral fracture healed with retrograde nail fixation, the left thigh pain
      resolved with prophylactic nail fixation, and pamidronate therapy was continued.
      Management options for femoral stress phenomena in patients on long-term
      bisphosphonates include discontinuation of the medication and prophylactic
      stabilization of the femur. Associated ipsilateral knee OA, present in our
      patient's case, may be a red herring in distal femoral stress phenomena. 

PMID- 24078946
TI  - Irreducible longitudinal distraction-dislocation of the hallux interphalangeal
      joint.
AB  - Although volar and dorsal dislocations have been described in the literature,
      dislocation of the hallux interphalangeal joint is a disorder rarely encountered
      by orthopedic and foot surgeons. In this article, we report a case of a distinct
      irreducible longitudinal distraction-dislocation that originally presented to the
      emergency department but required open reduction in the operating room. We also
      describe the presentation, anatomy, and treatment of this unique disorder. 

PMID- 24078947
TI  - Cartilage defect of lunate facet of distal radius after fracture treated with
      osteochondral autograft from knee.
AB  - We describe using an osteochondral autograft from the lateral femoral condyle of
      the knee to treat a symptomatic die-punch lesion of the lunate facet of the
      distal radius. An 18-year-old woman who sustained a distal radius fracture
      remained symptomatic after nonoperative treatment and diagnostic wrist
      arthroscopy with microfracture. We used a commercial harvesting system to
      transfer an osteochondral plug into a cartilage defect involving the lunate facet
      of the distal radius. At final follow-up, 34 months after surgery, the patient
      was assessed with a visual analog scale (VAS) and Disabilities of the Arm,
      Shoulder, and Hand (DASH) scores and with a comprehensive physical examination.
      Magnetic resonance arthrogram was used to assess articular cartilage status. VAS
      pain score improved from 7 before surgery to 0.5 after surgery. Postoperative
      DASH score was 0. The patient was asymptomatic and had satisfactory wrist motion
      without mechanical symptoms. Magnetic resonance arthrogram showed the transferred
      osteochondral autograft incorporated in excellent position. 

PMID- 24078948
TI  - Comparative effectiveness of joint reconstruction and fixation for femoral neck
      fracture: inpatient and 30-day mortality.
AB  - Although functional outcomes of hip joint reconstruction may be superior to those
      of internal fixation, differences in mortality between the 2 procedures are
      poorly defined. We conducted a retrospective study of patients 50 years and older
      with femoral neck fracture treated with joint reconstruction or internal
      fixation, performing adjusted logistic regressions to compare the odds of
      inpatient and 30-day mortality among patients according to surgery type. Of
      12,867 patients with femoral neck fracture, 9001 had joint reconstruction and
      3866 had internal fixation. After adjustment for patient factors alone, the odds
      of inpatient mortality were higher with reconstruction (OR, 1.62; 95% CI, 1.18
      2.23; P=.003); however, the difference in the odds of 30-day mortality did not
      achieve statistical significance (OR, 1.18; 95% CI, 1.00-1.41; P=.053).
      Controlling for patient and hospital factors, we found higher odds of both
      inpatient mortality (OR, 1.65; 95% CI, 1.19-2.28; P=.003) and 30-day mortality
      (OR, 1.22; 95% CI, 1.02-1.46; P=.026) with reconstruction. Joint reconstruction
      is associated with a 60% increase in the odds of inpatient mortality after
      femoral neck fracture. 

PMID- 24078949
TI  - Try before you buy: simulate, then operate.

PMID- 24078951
TI  - The future of medicine--are you prepared?

PMID- 24078950
TI  - RE: The Affordable Care Act: politics over policy.

PMID- 24078952
TI  - A comparison of standard and high-flexion knees: are we getting what we expected?
AB  - Some patients have been less than satisfied with flexion after total knee
      arthroplasty (TKA). As early designs provided limited flexion, companies have
      developed high-flexion designs. We conducted a study to compare flexion between 2
      standard and 3 high-flexion designs and to compare clinical and radiographic
      postoperative flexion. Clinical and radiographic measurements were obtained by 3
      independent orthopedists. Clinical flexion, with the patient maximally bending
      his or her knee as far as possible, was measured with a goniometer, recorded, and
      compared with measurements from lateral radiographs of the knee in the same
      position. A total of 144 knees (108 patients) were included in the study. Mean
      preoperative flexion was 110 degrees  for both groups, and mean postoperative
      flexion was 111 degrees  clinically and 109 degrees  radiographically for the
      standard designs, and 114 degrees  clinically and 117 degrees  radiographically
      for the high-flexion designs (P<.05). The groups had similar preoperative and
      postoperative Knee Society knee and function scores. Measurements obtained by the
      3 independent examiners were highly correlated. Compared with the standard
      designs, the highflexion designs demonstrated statistically significantly more
      flexion, though the clinical increase in flexion was relatively small (3o). 

PMID- 24078953
TI  - Student opinions on orthopedic residency selection, education, and work hours.
AB  - Other articles have been written about resident selection, musculoskeletal
      education, work hours, and call coverage, but none has described orthopedic
      applicants' opinions on these issues. We conducted a study to gain insight into
      applicants' attitudes about issues relevant to the specialty. We distributed a
      survey to 53 applicants interviewing for an orthopedic residency. The survey used
      both a multiple-choice format and a Likert scale ranging from 1 (strongly
      disagree or least important) to 5 (strongly agree or most important). Respondents
      rated the adequacy of musculoskeletal education in medical school a mean standard
      deviation (SD) of 2.00 (0.8) on the Likert scale. Ranking the factors most
      valuable to an orthopedic surgery application, they rated United States Medical
      Licensing Examination (USMLE) Step 1 board examination scores a mean (SD) of 4.26
      (0.9). In addition, of the 53 respondents, 46 (87%) anticipated working as a
      resident more than 80 hours per week, and 36 (68%) anticipated working as an
      attending 60 to 70 hours per week or less. Respondents also agreed that they
      should receive compensation for call coverage. Therefore, students agreed that
      medical school education is insufficient, rated USMLE scores the most important
      application factor, anticipated working more than 80 hours per week, and agreed
      that call coverage should be compensated. 

PMID- 24078954
TI  - Retrospective study of scapular notches in reverse shoulder arthroplasties.
AB  - We conducted a retrospective study of 36 patients with reverse shoulder
      prostheses to assess whether placement of the glenoid component affected
      development of scapular notches. Minimum follow-up was 2 years. Glenosphere
      position and its relation to scapular notching was analyzed radiographically. The
      glenosphere overhung the inferior glenoid rim in 19 cases (52.8%) and was flush
      with the rim in the other 17 cases (47.2%). A scapular notch developed in 13
      (36.1%) of the 36 cases. The notch developed in 8 (42.1%) of the 19 cases in
      which the glenosphere overhung the inferior rim, and in 5 (29.4%) of the 17 cases
      in which the glenosphere was flush with the rim. There were no significant
      differences (P = .601) between the 2 groups (overhanging vs flush glenoid
      component) with respect to development of scapular notching. Preoperative and
      postoperative Constant-Murley Shoulder Outcome scores were 19.42 and 49.21 for
      the group with scapular notches, and 25.09 and 51.96 for the group without
      notches. From a clinical viewpoint, there were no significant differences in
      scapular notch development and functional Constant-Murley Shoulder Outcome scores
      between glenospheres overhanging the glenoid rim and glenospheres flush with the
      glenoid rim. 

PMID- 24078955
TI  - Diagnosing segmental wedge fracture of the tibia before performing intramedullary
      nailing.
AB  - Tibial shaft fractures with a wedge butterfly segment are often repaired with
      intramedullary fixation. At the time of presentation, the fragment may appear
      benign on radiographs as a portion of the cortical bone in an acceptable
      position. However, a segment that includes the entire circumference of the tibial
      cortex can be a problem during surgical stabilization. This ring effect will
      demand cannulation of the butterfly segment with the guide wire before rod
      insertion. Since computed tomography is not always necessary for minimally
      displaced fractures, this issue may not be discovered until surgery. Lack of
      cannulation may lead to painful nonunion. Preoperative recognition of this
      fracture pattern and intraoperative butterfly cannulation will improve the
      postoperative stability of this fracture. 

PMID- 24078956
TI  - Rare combination of ipsilateral acetabular fracture-dislocation and
      pertrochanteric fracture.
AB  - Acetabular fracture-dislocations are severe injuries that require urgent closed
      reduction of the hip and often require surgery to restore hip stability. Other
      authors have described acetabular fracture-dislocations associated with femoral
      neck fractures, but to our knowledge, this case report is the first to describe
      an acetabular fracture-dislocation in association with an ipsilateral
      pertrochanteric fracture and subtrochanteric extension. The polytraumatized
      patient initially was not stable enough for prolonged surgery. Through a 3-cm
      anterolateral hip incision, a 5-mm Schanz screw was introduced percutaneously
      into the femoral head through the primary fracture site under fluoroscopic
      guidance. With inline traction on the leg, the Schanz screw was used to
      manipulate the femoral head back into the acetabular fossa. The Schanz screw was
      removed, the head remained reduced, and a skeletal traction pin was placed to
      maintain length and alignment of the pertrochanteric fracture until definitive
      stabilization was possible. We propose a staged treatment strategy consisting of
      early closed reduction of the hip, and after the patient has been stabilized,
      reduction and fixation of the fractures. This strategy may be useful in managing
      an unstable polytraumatized patient or a patient who requires prolonged transfer
      to receive definitive care. 

PMID- 24078957
TI  - Progressive hematoma in an older adult: closed internal degloving injury of the
      knee.
AB  - Closed internal degloving injury of soft-tissues has been reported in the pelvic
      acetabular area after high-velocity trauma. More recently, this lesion has been
      reported in the knees of young athletes involved in contact sports. The injury is
      often brought late to the notice of the clinician, and sometimes the diagnosis is
      missed. Effective treatment relies heavily on clinical examination, and magnetic
      resonance imaging is helpful as a diagnostic tool. Treatment may depend on time
      between injury and presentation, patient age, collection severity, and the
      effects of previous treatment. Lesions that threaten skin vascularity and show
      rapid progression require emergency management. Minimally invasive techniques are
      preferred over extensive procedures. Elderly patients need to be observed for
      progression of the initial lesion and development of late complications, which
      may require emergency intervention. Clinicians should tailor the rehabilitation
      protocol to the patient's age and the severity of the lesion. This case report of
      a 55-year-old female patient covers the nature, diagnosis, and management of a
      progressively dissecting hematoma that evolved into a massive closed internal
      degloving lesion. 

PMID- 24078958
TI  - High-pressure paint gun injection injury to the palm.
AB  - High-pressure injection injuries often have a misleadingly benign presentation.
      However, it is important to recognize the potential surgical urgency and long
      term sequelae associated with these injuries. We present a case of paint gun
      injection to the palm and review the literature on high-pressure paint injection
      injuries. The 3 factors most important for the fate of the limb are material
      type, injection pressure, and injury site. The immediate use of antibiotics and
      tetanus prophylaxis, with or without steroids, is indicated. Urgent debridement
      in the operating room is imperative and can decompress the neurovascular
      structures and flexor tendon sheath by removing the irritating agents. Reported
      overall amputation rates have been as high as 30%. 

PMID- 24078959
TI  - The pros and cons of using larger femoral heads in total hip arthroplasty.
AB  - With the introduction of improved bearing surfaces for total hip arthroplasty
      (THA) has come a reintroduction of larger femoral heads with the promise of
      reducing the rate of hip instability and increasing hip range of motion (ROM).
      The size of femoral heads used for THA ranges from 22 to 40 mm, and even larger
      heads are used for hip resurfacing. With accurately positioned components, larger
      heads reduce the hip instability rate and theoretically increase hip ROM.
      However, for any given bearing surface, the volumetric wear rate is higher for
      larger heads than for smaller heads, which potentially jeopardizes the long-term
      survival of these reconstructions. In this article, we review the evidence for
      use of larger femoral heads with respect to stability, ROM, impingement, wear
      rate, bearing surfaces, and future directions. 

PMID- 24078961
TI  - Calcium pyrophosphate dihydrate crystal deposition disease (pseudogout) of lumbar
      spine mimicking osteomyelitis-discitis with epidural phlegmon.
AB  - Calcium pyrophosphate dihydrate crystal deposition disease (pseudogout) of the
      axial spine is rare. To our knowledge, there are few reports of the disease
      presenting with a presumed diagnosis of infection in the lumbar spine. As
      reported here, the diagnosis of osteomyelitis-discitis with epidural phlegmon was
      presumed before intervention. We present the case of a 60-year-old man with
      radiographic imaging and worsening clinical presentation at 2 consecutive
      hospitalizations. Axial magnetic resonance imaging originally showed increased
      signal intensity at the L5-S1 disk, which suggested an infectious rather than
      inflammatory process. Aspiration and biopsy at the time were nondiagnostic and
      showed no evidence of organisms. Two months after conservative treatment, the
      patient was readmitted with intractable low back pain and radiating bilateral leg
      pain. Repeat imaging showed increased interval signal in the L5-S1 disk, as well
      as enhancing soft-tissues that now extended to adjacent levels with extensive
      erosive changes. After surgical intervention for suspected infection, all
      cultures and stains for organisms were negative. Final pathology showed
      granulation tissue with focal inflammatory changes and calcium pyrophosphate
      crystal deposition. Although pseudogout is rare, physicians should add the
      disorder to the differential diagnosis for low back pain with radiculopathy and
      presumed infection. 

PMID- 24078960
TI  - Pancarpal synovial and tenosynovial chondromatosis in a 65-year-old man: a highly
      unusual presentation of a common condition.
AB  - Synovial chondromatosis is a rare, benign, metaplastic condition in which
      synovial tissue becomes hyperplastic, and foci of cartilaginous metaplasia
      develop in the synovial membranes of joints, bursae, or tendon sheaths.
      Involvement is most commonly monoarticular. The large joints are most commonly
      affected, with the knee accounting for more than half of all cases. There are
      isolated reports of synovial chondromatosis occurring in the small joints of the
      wrist and hand. However, it is very uncommon for the disease to involve multiple
      different synovial structures. We report the case of a middle-aged man with
      pancarpal synovial chondromatosis with involvement of numerous bony, articular,
      and tenosynovial structures within the hand and wrist. 

PMID- 24078962
TI  - Publish or perish; but what, when, and how?

PMID- 24078963
TI  - Avoiding unplanned resections of wrist sarcomas: an algorithm for evaluating
      dorsal wrist masses.
AB  - Ganglion cysts, soft-tissue masses that commonly occur about the wrist, are often
      excised without imaging or biopsy. In this article, we report a series of
      incompletely excised soft-tissue sarcomas about the wrist and offer an algorithm
      for their evaluation. We describe a series of 4 consecutive patients who each
      presented after incomplete resection of a soft-tissue sarcoma mistakenly
      diagnosed as a ganglion cyst. We also retrospectively review the cases of 7
      patients with incompletely excised sarcomas of the wrist. Three of the 4 patients
      with sarcomas mistaken for ganglion cysts did not have prior magnetic resonance
      imaging (MRI), 3 of the 4 did not have an attempted aspiration, and all 4 did not
      have transillumination. Common atypical characteristics included ulna-based
      lesions (3/4), symptoms for less than 6 months (3/4), and no appreciable
      fluctuation in size (3/4). Functional outcomes for all patients were poor because
      of multiple surgical procedures, re-excisions requiring flaps, and need for
      additional adjuvant therapies. Dorsal wrist masses with atypical characteristics
      should be approached with caution. Transillumination and aspiration are 2
      accessible, cost-efficient methods for evaluating these masses. If either test is
      abnormal, an MRI should be performed. 

PMID- 24078964
TI  - Saline-coupled bipolar sealing in revision total knee arthroplasty for infection.
AB  - Blood conservation with saline-coupled bipolar sealing devices in primary total
      knee arthroplasty (TKA) has had mixed results. Moreover, investigators have not
      studied these devices in infected TKA cases in which conventional methods of
      blood management cannot be used. We conducted a single-surgeon, case-control
      study to evaluate how the choice of an electrocautery device affects total blood
      loss, transfusion requirements, and total cost in revision TKA for infection.
      Each of the 80 patients in the study had an infected TKA and underwent surgery
      that involved the use of a saline-coupled bipolar sealing device at our
      institution. Results were compared with those of a control group of 40 patients
      immediately predating use of this device. Groups were matched for age, body mass
      index, American Society of Anesthesiologists (ASA) classification, and surgery
      type. We then compared the groups on multiple variables, including total blood
      loss, transfusion requirements, operative time, and hemoglobin decrease. The
      groups did not differ with respect to blood loss or transfusion requirements.
      However, operative time was significantly lower in the bipolar sealer group. This
      difference translated to an average net additional cost of about $70 per case.
      Given the results of this study, use of a saline-coupled bipolar sealing device
      in patients with infected TKAs is not clinically or economically justified. 

PMID- 24078965
TI  - Propensity for hip dislocation in normal gait loading versus sit-to-stand
      maneuvers in posterior wall acetabular fractures.
AB  - Treatment of posterior wall (PW) fractures of the acetabulum is guided by the
      size of the broken wall fragment and by hip instability. Biomechanical testing of
      hip instability typically is done by simulating the single-leg-stance (SLS) phase
      of gait, but this does not represent daily activities, such as sit-to-stand (STS)
      motion. We conducted a study to examine and compare hip instability after PW
      fractures in SLS and STS loading. We hypothesized that wall fragment size and
      distance from the dome (DFD) of the acetabulum to the simulated fracture would
      correlate with hip instability and, in the presence of a PW fracture, the hip
      would be more unstable during STS loading than during SLS loading. Incremental PW
      osteotomies were made in 6 cadaveric acetabula. After each osteotomy, a 1200-N
      load was applied to the acetabulum to simulate SLS and STS loading until
      dislocation occurred. All hip joints in the cadaveric models were more unstable
      in STS loading than in SLS loading. PW fragments at time of dislocation were
      larger (P<.001) in SLS loading (85% +/- 13%; range, 81%-100%) than in STS loading
      (40% +/- 7%; range, 33%-52%). Mean (SD) DFD at time of dislocation was 15.0 (3.5)
      mm (range, 14.4-19.6 mm) in STS loading and 5.3 (4.3) mm (range, 0.1-10.0 mm) in
      SLS loading (P<.04). There was more hip instability in STS loading than in SLS
      loading. In STS loading, hips dislocated with a PW fracture size of 33% or more
      and a DFD of 20 mm or less. 

PMID- 24078966
TI  - Evaluating factors affecting patellar component fixation strength in total knee
      arthroplasty.
AB  - Complications related to the patellofemoral joint after total knee arthroplasty
      (TKA) represent up to 50% of TKA reoperations. Shear forces across the knee
      produce wear and occasionally result in failure of fixation of all-polyethylene
      patellar components. We conducted a study to evaluate the effect of 2 factors on
      the shear strength of patellar component fixation: time between cement mixing and
      application of the patellar component, and amount of pressure applied during
      implantation. Fifty-four patellae were harvested from 27 cadavers and were
      prepared as for a TKA, allowing 3 different amounts of time for the cement to set
      or cure before application, and using 3 different pressures. The patellae were
      mounted and tested for fixation strength with a materials testing machine.
      Fixation was significantly stronger (P = .006) at 42 pounds of pressure after
      curing the cement for 8 minutes (compared with 2 minutes) and was significantly
      stronger (P = .005) after 2 minutes of curing at 42 pounds of pressure (compared
      with 62 pounds of pressure). We concluded that allowing the cement to cure while
      cementing the femoral and tibial components does not jeopardize fixation of the
      patellar component and that excessive compression of a patellar clamp may weaken
      fixation. 

PMID- 24078967
TI  - Extranodal Rosai-Dorfman disease as solitary lesion of the tibia in a 56-year-old
      woman.
AB  - We report the case of a 56-year-old woman who had severe leg pain and whose
      radiographs initially suggested metastatic carcinoma, lymphoma, osteogenic
      sarcoma, or adamantinoma. Results of multiple biopsies confirmed a diagnosis of
      Rosai-Dorfman disease, which typically presents in children and young adults
      (mean age at onset, 20 years). 

PMID- 24078968
TI  - New anticoagulants for thromboprophylaxis after total knee arthroplasty.
AB  - Total knee arthroplasty (TKA) is one of the most common orthopedic procedures in
      the United States. The number of TKAs is expected to rise significantly over the
      next 2 decades. One of the most common complications after TKA is venous
      thromboembolism (VTE), which is potentially fatal. The incidence of VTE is
      effectively reduced by prophylactic anticoagulants, and clinical guidelines have
      been developed to improve VTE management. However, current anticoagulants have
      limitations in terms of efficacy, safety, half-life, ease of administration, and
      patient adherence. Moreover, these anticoagulants require routine monitoring and
      dose adjustment, and potential bleeding complications represent an important
      concern. A new generation of anticoagulants, including recently approved
      rivaroxaban, is being developed to address the shortcomings of current agents.
      The efficacy and safety of these newer agents are comparable with those of
      existing ones. Rivaroxaban is the only new oral agent that is approved for use in
      TKA and that has demonstrated an efficacy superior to that of enoxaparin in phase
      3 trials. To optimize the management of VTE prophylaxis after TKAs, orthopedic
      surgeons must have a thorough understanding of these new oral agents. 

PMID- 24078969
TI  - The half-pin and the pin tract: a survey of the Limb Lengthening and
      Reconstruction Society.
AB  - Although the key principles of external fixation have changed little over the
      years, there remains a significant amount of variation in fixation methods and
      postoperative care. In particular, use and management of half-pins intended for
      prolonged reconstruction are the subject of strong opinions and intense debate.
      We conducted a study of common trends in use and management of half-pins and in
      treatment of pin-tract infections in circular fixation by polling subject matter
      experts who are members of the Limb Lengthening and Reconstruction Society.
      Although the distribution of stainless steel half-pins (52%) and titanium half
      pins (48%) was similar, most respondents preferred hydroxyapatite coating (81%).
      Respondents commonly encouraged use of a shower (60%) and a washing solution
      (67%) for pin-site care. For pin-tract infections, oral antibiotics were
      prescribed more often (83%) than parenteral antibiotics (17%) and were given for
      8 days on average. Results from this study helped identify trends in application
      techniques and in routine management of circular fixators. In addition, they
      helped identify several areas of clinical equipoise that should be studied,
      including metallurgy, pin-site care solutions, and antibiotics. 

PMID- 24078970
TI  - Repair of lumbar dural tears with a suture patch: retrospective single-surgeon
      case series.
AB  - Dural tears traditionally have been treated with repair and then flat bed rest of
      variable duration. We conducted a study to evaluate the outcome of treating dural
      tears with a suture patch and immediate mobilization. Fifty patients (28 male, 22
      female) had a lumbar dural tear repaired with suture patch and immediate
      mobilization. Mean age was 58.9 years (range, 31-81 years). Medical records were
      reviewed to determine the rate of signs and symptoms: headache, photophobia,
      tinnitus, neck pain, incisional fluctuance, wound drainage, and return to
      operating room. No patients reported postoperative headache, photophobia,
      tinnitus, or neck pain. No patients developed wound fluctuance or drainage. One
      patient was treated medically for a superficial wound infection. No patients
      required return to the operating room. Dural repair with suture patch appears to
      be effective and allows early mobilization. 

PMID- 24078971
TI  - Neck-shoulder crossover: how often do neck and shoulder pathology masquerade as
      each other?
AB  - Cases of consecutive new patients seen at orthopedic spine and shoulder clinics
      were reviewed. Four percent of spine patients had significant shoulder pathology,
      and 3.6% of shoulder patients had significant spine pathology. Identification of
      the correct pain generator is a prerequisite for effective treatment in patients
      with neck and/or shoulder problems. However, distinguishing between the two can
      be difficult. Relative frequencies of how often one is mistaken for the other
      have not been well established. Six hundred ninety-four new patients were seen at
      the orthopedic shoulder clinic (n = 452) or spine clinic (n = 242) at an academic
      institution during a 2-year period. One hundred seven patients had previous
      shoulder surgery, and 39 had previous neck surgery. The 548 patients (shoulder
      clinic, 345; spine clinic, 203) who had no previous surgery were reviewed with
      respect to workup performed, final diagnosis, subsequent operative procedures,
      and incidence of referral from the shoulder clinic to the spine clinic and vice
      versa. Among the patients seen at the shoulder clinic, 325 (94.2%) had shoulder
      pathology, 6 (1.7%) had neck but no shoulder pathology, 6 (1.7%) had shoulder and
      neck pathology, and 8 (2.3%) had an unidentifiable cause of pain. Of the 12
      patients with neck pathology, none underwent neck surgery. Among the patients
      seen at the spine clinic, 182 (89.7%) had neck pathology, 5 (2.5%) had shoulder
      but no neck pathology, 3 (1.5%) had neck and shoulder pathology, and 13 (6.4%)
      had an unidentifiable cause of pain. Of the 8 patients with shoulder pathology, 1
      (12.5%) underwent shoulder surgery. Our analysis suggests that for patients who
      present to a shoulder surgeon's clinic for shoulder pain, 3.6% will turn out to
      have neck pathology. For patients who present to a spine surgeon's clinic for
      neck pain, 4% may turn out to have shoulder pathology. Thus, approximately 1 in
      25 patients seen at a surgeon's clinic for a presumed shoulder or neck problem
      may exhibit neck-shoulder crossover, in which pathology in one may be mistaken
      for or coexist with the other. 

PMID- 24078972
TI  - Traumatic obturator hip dislocation in a 9-year-old boy.
AB  - Traumatic hip dislocation is a rare but potentially devastating injury in a
      child. Although most hip dislocations are posterior, other variants have been
      described. An anterior dislocation in the pediatric population is uncommon and,
      to our knowledge, this is the first case of anterior-inferior (obturator)
      dislocation (ie, the femoral head lies in the obturator foramen), to be reported
      in the English-language literature. In this article, we describe the case of a
      young boy with a traumatic obturator hip dislocation treated conservatively with
      closed reduction and followed closely for 1 year. The patient did not develop any
      sequelae throughout the follow-up year. This case report, along with a review of
      the literature, will help guide clinicians in the care of patients with this rare
      injury. 

PMID- 24078973
TI  - Editorial: more clinically relevant and more evidence based: a new look for
      Quintessence International.

PMID- 24078974
TI  - Loss of vertical dimension: extensive therapy in dentitions with erosion and
      abrasion.
AB  - There has been an increase in the incidence of tooth structures altered through
      abrasion and erosion. Such patients need to be offered adequate treatment. This
      case report shows that consistent treatment planning leads to functional and
      esthetic rehabilitation, even in cases with severe tooth wear. 

PMID- 24078975
TI  - Clinical outcomes following subgingival application of a novel erythritol powder
      by means of air polishing in supportive periodontal therapy: a randomized,
      controlled clinical study.
AB  - OBJECTIVES: The aim of this prospective, randomized, controlled clinical study
      was to compare the clinical outcomes of the subgingival treatment with erythritol
      powder by means of an air-polishing (EPAP) device and of scaling and root planing
      (SRP) during supportive periodontal therapy (SPT). METHOD AND MATERIALS: 40
      patients enrolled in SPT were randomly assigned to two groups of equal size.
      Sites had to show signs of inflammation (bleeding on probing [BOP]-positive) and
      a probing pocket depth (PPD) of >= 4 mm, however, without presence of detectable
      subgingival calculus. During SPT, these sites were treated with EPAP or SRP,
      respectively. Full mouth and site-specific plaque indices, BOP, PPD, and clinical
      attachment level (CAL) were recorded at baseline (BL) and at 3 months, whereas
      the percentage of study sites positive for BOP (BOP+) was considered as primary
      outcome variable. Additionally, patient comfort using a visual analog scale (VAS)
      and the time needed to treat per site was evaluated. RESULTS: At 3 months, mean
      BOP level measured 45.1% at test sites and 50.6% at control sites, respectively,
      without a statistically significant difference between the groups (P > .05). PPD
      and CAL slightly improved for both groups with comparable mean values at 3
      months. Evaluation of patient tolerance showed statistically significantly better
      values among patients receiving the test treatment (mean VAS [0-10], 1.51)
      compared to SRP (mean VAS [0-10], 3.66; P = .0012). The treatment of test sites
      was set to 5 seconds per site. The treatment of control sites, on the other hand,
      lasted 85 seconds on average. CONCLUSION: The new erythritol powder applied with
      an air-polishing device can be considered a promising modality for repeated
      instrumentation of residual pockets during SPT. CLINICAL RELEVANCE: With regard
      to clinical outcomes during SPT, similar results can be expected irrespective of
      the two treatment approaches of hand instrumentation or subgingival application
      of erythritol powder with an air-polishing device in sites where only biofilm
      removal is required.

PMID- 24078976
TI  - Massive bleeding from a gastric varix coil migration in a liver transplant
      patient.

PMID- 24078977
TI  - A rare case of intestinal obstruction.

PMID- 24078978
TI  - Challenges in organizing a transplantation system.

PMID- 24078979
TI  - Red pepper: from the kitchen to the pharmacy.

PMID- 24078980
TI  - Capsule endoscopy for colorectal cancer and polyp screening.

PMID- 24078981
TI  - Role of Helicobacter pylori infection in the thyroid diseases.

PMID- 24078982
TI  - Risk of colorectal cancer in Crohn's disease patients with colonic involvement
      and stenosing disease in a population-based cohort from Hungary.
AB  - BACKGROUND & AIMS: Since data is limited regarding the risk of colorectal cancer
      (CRC) in Crohn's disease (CD) patients who present with stenosing disease in the
      colon, this study was undertaken to assess CRC risk in such patients, using a
      population-based, Veszprem province database, which includes incidental patients
      diagnosed between January 1, 1977 and December 31, 2011. METHODS: Data from 640
      incidental CD patients were analyzed (M/F ratio: 321/319, age-at-diagnosis: 28
      years (IQR: 22-38)). Both hospital and outpatient records were collected and
      comprehensively reviewed. RESULTS: CRC was diagnosed in six CD patients during a
      follow-up of 7759 person-years. Sixty-two patients presented with
      colonic/ileocolonic disease and a stenotic lesion in the colon with a follow-up
      of 702 person-years (median: 10.5, IQR: 5-16years). Colorectal cancer developed
      in 6.5% (equalling 0.57/100 person-years), the SIR (6.53, 95% CI: 2.45-17.4) was
      increased with four patients observed versus 0.61 expected. In a Kaplan-Meier
      analysis, the probability of developing CRC was 5.5% and 7.5% after 5- and 10
      years, respectively, versus 0.4% in patients with other phenotypes (HR: 18.8,
      p<0.001). A sensitivity analysis included patients with stenosing colonic lesion
      at diagnosis or during follow-up (n=91, follow-up: 1180 person-years, median: 12,
      IQR: 6-17years). The probability of developing CRC was 3.6% and 4.9% after 5- and
      10 years, respectively. CONCLUSIONS: The risk of CRC in CD patients presenting
      with or developing a stenotic lesion in the colon is high even after a short
      disease duration, suggesting the need for careful surveillance.

PMID- 24078983
TI  - Infectious complications of TNF-alpha inhibitor monotherapy versus combination
      therapy with immunomodulators in inflammatory bowel disease: analysis of the Food
      and Drug Administration Adverse Event Reporting System.
AB  - BACKGROUND & AIM: Incremental increase in the risk of serious infections with
      combinations of tumor necrosis factor-alpha (TNF-alpha) inhibitors and
      immunomodulators compared to monotherapy with these agents in inflammatory bowel
      disease (IBD) is unclear. Our aim was to analyze whether there is such an
      incremental increase in the odds of serious infections. METHODS: The FDA Adverse
      Event Reporting System (2003 - June 2011) was queried for 'Primary Suspect'
      reports of various infections with TNF-alpha inhibitors, systemic corticosteroids
      and immunomodulators with usage indication of IBD. Odds ratios (ORs) were
      calculated for baseline odds of infections as well as serious infections
      (requiring hospitalization and/or death) with monotherapy and combination therapy
      (compared to 5-Aminosalicylates) as well as incremental increase in odds for dual
      or triple combination therapy (compared to monotherapy or dual combination
      therapy respectively) using Fisher's exact test with SPSS 20 (IBM Co. Armonk, NY,
      USA). RESULTS: TNF-alpha inhibitor (OR 1.95; CI, 1.06-3.59) and immunomodulator
      (OR 9.99; CI, 1.28-78.16) monotherapy as well as in combination augmented
      baseline odds of serious infection for IBD patients. No incremental increase in
      the odds with combination therapy was seen when an immunomodulator was added to a
      TNF-alpha inhibitor (OR 0.37; CI, 0.05-2.80) and when both were used with a
      systemic corticosteroid (OR 0.91; CI, 0.50-1.66). Variations in these were seen
      for the individual infection subtypes. CONCLUSIONS: TNF-alpha inhibitor and
      immunomodulator monotherapy increase the baseline odds of acquiring a serious
      infection. Combination therapy with these drugs does not further increase the
      odds of serious infections compared to monotherapy.

PMID- 24078984
TI  - Oral glutamine challenge improves the performance of psychometric tests for the
      diagnosis of minimal hepatic encephalopathy in patients with liver cirrhosis.
AB  - BACKGROUND & AIMS: Minimal hepatic encephalopathy is difficult to diagnose due to
      the lack of a gold standard test. Oral glutamine challenge has been found to
      increase blood ammonia in cirrhosis leading to secondary cognitive impairment.
      The aim of this study was to evaluate the value of oral glutamine challenge in
      improving the psychometric performance for the diagnosis of minimal hepatic
      encephalopathy, and the risk of this condition for overt hepatic encephalopathy
      in cirrhotic patients. METHODS: Fifty-four cirrhotics (34 males; mean age 55.2
      years) and 16 healthy controls were included. Minimal hepatic encephalopathy was
      assessed by the psychometric hepatic encephalopathy score. Arterial ammonia
      concentrations and psychometric tests were evaluated 60 minutes before and after
      a 20 g oral glutamine load. Follow-up lasted 12 months. RESULTS: At baseline, 29
      (53.7%) of 54 patients had minimal hepatic encephalopathy and significantly more
      (79.63%) post-glutamine (p<0.0001). Baseline arterial ammonia levels
      significantly raised post-glutamine in cirrhotics (85.2+/-20.8MUg/dL versus
      159.82 +/- 66.01MUg/dL, p<0.0001), while in controls they remained unchanged
      (p=0.064). For the diagnosis of minimal hepatic encephalopathy, baseline arterial
      blood ammonia showed an area under the ROC curve of 0.54 (CI95%: 0.402-0.680,
      p=0.58), with no significant post-glutamine changes (0.53, CI95%: 0.389-0.667,
      p=0.77). Ten patients (18.51%) developed overt hepatic encephalopathy, among
      which 9 had minimal hepatic encephalopathy (4 at baseline, 5 post-glutamine). At
      multivariate analysis, MELD score (1.5187, CI95%: 1.0690-2.1574, p=0.0197) was an
      independent predictor of the overt hepatic encephalopathy. CONCLUSIONS: In
      cirrhotic patients, an oral glutamine load improves the psychometric diagnostic
      performance for minimal hepatic encephalopathy. MELD score has been independently
      related to overt hepatic encephalopathy.

PMID- 24078985
TI  - Transient elastography for the detection of hepatocellular carcinoma in viral C
      liver cirrhosis. Is there something else than increased liver stiffness?
AB  - BACKGROUND & AIMS: Liver stiffness (LS) is increased in liver cirrhosis, higher
      values being associated with complications, among them the development of
      hepatocellular carcinoma (HCC). However, LS values alone cannot accurately
      differentiate patients with HCC. Therefore, our aim was to study the performance
      of LS measurement data and common biomarkers for the detection of HCC in HCV
      related liver cirrhosis. METHODS: We performed a case matching study comparing
      HCV cirrhotic patients with and without HCC (72 in each group) that were
      identical in terms of sex, age, BMI and duration of HCV infection. All patients
      underwent LS measurement, endoscopy, liver imaging and liver function tests. A
      multiple regression analysis was performed and a HCC detection model was
      calculated, which was further validated in another group of 40 HCV infected
      cirrhotics, of whom 52% had HCC. RESULTS: In the HCC group, LS was significantly
      higher (42 vs 27 kPa, p<0.0001). In the multivariate analysis higher values of
      LS, alanine-aminotransferase (ALAT), alpha-fetoprotein (AFP) and interquartile
      range (IQR) of LS measurements were independently associated with the presence of
      HCC (p<0.0001 for all parameters; Odds Ratios of 8.27, 1.01, 1.04 and 1.16,
      respectively). The detection model combining the four variables showed a good
      diagnostic performance in both training and validation groups, with AUROCs of
      0.86 and 0.8, respectively. All variables were also positively correlated with
      tumor size. CONCLUSION: In HCV related cirrhosis, HCC is associated with
      increased LS and IQR values and high ALAT and AFP levels. By combining these four
      parameters into a regression model, liver cancer may be noninvasively predicted
      with good accuracy.

PMID- 24078986
TI  - Treatment of hepatocellular carcinoma in a tertiary Romanian center. Deviations
      from BCLC recommendations and influence on survival rate.
AB  - BACKGROUND & AIM: The Barcelona-Clinic Liver Cancer (BCLC) staging system is
      based on the results obtained in the setting of several cohort studies and
      randomized clinical trials. We have evaluated the applicability of the BCLC
      staging system and the effect of treatment allocation according to BCLC on the
      survival rate and prognosis in patients with hepatocellular carcinoma (HCC) in a
      tertiary center. METHODS: Treatment indications for 473 patients referred to our
      center with the diagnosis of HCC were retrospectively analyzed. Patients were
      split in three groups: a group treated according to BCLC recommendation, an
      overtreated group and an undertreated group. The survival rate was calculated
      using the Kaplan Meier method and compared using the log-rank test. RESULTS:
      Patients distribution according to BCLC staging system was: 17 patients (3.6%) in
      very early stage (O), 161 (34.0 %) in early (A), 140 (29.6%) in intermediate (B),
      82 (17.3%) in advanced (C) and 73 patients (15.4%) in terminal stage (D). Only
      275 patients (58.1%) from stage 0, A-D were treated according to BCLC. The mean
      survival rate in stage 0 and A was higher for patients receiving curative
      treatment in comparison with undertreated patients (41 vs 28 months, p< 0.05).
      Overtreated patients in stage B or C had a better survival than patients treated
      according to BCLC (25 months vs 21 months, p=0.973, and 28 months vs 4 months,
      p=0.308, respectively), without statistical significance. Patients in stage B and
      C treated according to BCLC recommendations had a better survival than those
      undertreated (21 months vs 13 months, p=0.002, and 4 vs 3 months, p=0.036,
      respectively). CONCLUSIONS: Deviations from BCLC recommendations occur in 40% of
      patients with HCC. Undertreatment results in a decreased survival of patients
      diagnosed with HCC. Overtreated BCLC-B and C patients have an increased survival
      in comparison with those treated with standard therapy.

PMID- 24078988
TI  - Aflatoxins as a cause of hepatocellular carcinoma.
AB  - Aflatoxins, metabolites of the fungi Aspergillus flavus and Aspergillus
      parasiticus, are frequent contaminants of a number of staple foods, particularly
      maize and ground nuts, in subsistence farming communities in tropical and sub
      tropical climates in sub-Saharan Africa, Eastern Asia and parts of South America.
      Contamination of foods occurs during growth and as a result of storage in
      deficient or inappropriate facilities. These toxins pose serious public health
      hazards, including the causation of hepatocellular carcinoma by aflatoxin B1.
      Exposure begins in utero and is life-long. The innocuous parent molecule of the
      fungus is converted by members of the cytochrome p450 family into mutagenic and
      carcinogenic intermediates. Aflatoxin-B1 is converted into aflatoxin B1-8,9 exo
      epoxide, which is in turn converted into 8,9-dihydroxy-8-(N7) guanyl-9-hydroxy
      aflatoxin B1 adduct. This adduct is metabolized into aflatoxin B1
      formaminopyrimidine adduct. These adducts are mutagenic and carcinogenic. In
      addition, an arginine to serine mutation at codon 249 of the p53 tumor suppressor
      gene is produced, abrogating the function of the tumor suppressor gene, and
      contributing to hepatocarcinogenesis. Aflatoxin B1 acts synergistically with
      hepatitis B virus in causing hepatocellular carcinoma. A number of interactions
      between the two carcinogens may be responsible for this action, including
      integration of hepatitis B virus x gene and its consequences, as well as
      interference with nucleotide excision repair, activation of p21waf1/cip1,
      generation of DNA mutations, and altered methylation of genes. But much remains
      to be learnt about the precise pathogenetic mechanisms responsible for aflatoxin
      B1-induced hepatocellular carcinoma as well as the interaction between the toxin
      and hepatitis B virus in causing the tumor. 

PMID- 24078987
TI  - Dynamics of the Romanian waiting list for liver transplantation after changing
      organ allocation policy.
AB  - AIM: The aim of the present study was to characterize the dynamics of the
      Romanian waiting list (WL) for liver transplantation (LT) over two periods: 2004
      2007 vs. 2008-2011. METHODS: 1,085 patients listed for LT during the time period
      2004-2011 were included in our analysis. RESULTS: Death on the WL was
      significantly higher before 2008 (37% vs. 26.4%, p=0.0001) and risk of dying
      while on WL was 60% higher. Waiting time on the WL was 75% longer and time until
      LT was 102% longer before 2008 compared to the second time period (p=0.0001).
      After 2008, 62.3% of patients were listed for LT with Child Pugh class C compared
      to 22.1% before 2008 (p<0.0001). CONCLUSION: A significant reduction of mortality
      has been registered on the Romanian WL for LT after 2008, despite the increased
      severity of liver disease in patients listed for LT.

PMID- 24078989
TI  - MicroRNA in colorectal cancer: new perspectives for diagnosis, prognosis and
      treatment.
AB  - Colorectal cancer (CRC) is a common condition and represents a lethal disease,
      following a sequential progression from adenoma to carcinoma. Interfering with
      such natural history of CRC offers clues to prevention and cure, but current
      screening methods for CRC are still limited by unsatisfactory sensitivity and
      specificity. Novel diagnostic, prognostic tools are therefore being actively
      investigated for CRC. The discovery of microRNAs (miRNAs) has led to active
      research focusing on their role in cancer and several crucial pathways involving
      angiogenesis, cancer-stem-cell biology, epithelial-mesenchymal transition,
      formation of metastasis, and drug resistance. MiRNAs might soon represent novel
      prognostic and diagnostic tools in patients at high risk of CRC or being
      diagnosed with CRC. MiRNA might prove useful also as therapeutic tools, since
      dysregulation of miRNAs in cancer cells results in higher levels of messenger RNA
      (mRNA) specific to tumor promoter genes or tumor suppressor genes. Thus, novel
      anticancer therapies might originate from manipulation of oncogenic or tumor
      suppressor miRNAs in CRC. In this review, the innovative aspects of miRNA are
      discussed, with respect to biogenesis, their role in CRC, and their potential use
      as biomarkers. Before miRNAs can become available in the clinical setting,
      however, a number of large prospective studies are still required. 

PMID- 24078990
TI  - Sentinel node mapping in anal canal cancer: systematic review and meta-analysis.
AB  - BACKGROUND & AIMS: The pathological condition of inguinal lymph nodes is an
      independent prognostic factor in predicting tumor recurrence and overall survival
      in anal canal cancer. Sentinel node mapping is a non-invasive method for the
      detection of inguinal lymph node involvement in anal cancer. In the current
      study, we conducted a comprehensive search of literature in this regard and then
      interpreted the final results in a systematic review and meta-analysis format.
      METHODS: Medline, SCOPUS, and ISI Web of Knowledge were searched with the
      following search terms: (anal OR anus) AND sentinel. Outcomes of interest were
      inguinal detection rate and inguinal recurrence in patients receiving inguinal
      sparing radiotherapy due to pathologically negative inguinal sentinel nodes
      (false negative cases). RESULTS: Overall 16 studies (323 patients) were included
      in the meta-analysis. Pooled inguinal detection rate was 86.2%: 73.4-93.4%: for
      studies using both blue dye and radiotracer it was 90.1% [78.7-95.8] and for
      studies using radiotracer alone it was 72.4% [46.3-88.9]. Pooled sensitivity was
      90% [79-97%]. CONCLUSIONS: Sentinel node biopsy is a promising method for
      inguinal lymph node staging in anal cancer. Combined blue dye and radiotracer
      technique can maximize the inguinal detection rate. Location of the tumor is
      highly associated with the detection of inguinal sentinel nodes. Despite fairly
      high pooled sensitivity, no definite conclusion can be made regarding false
      negative rate of this technique due to low sample size and sub-optimal quality of
      the included studies. Large multicenter studies with long and consistent follow
      up are needed to definitely validate this technique in the future.

PMID- 24078991
TI  - An invasive extragastrointestinal stromal tumor curably resected following
      imatinib treatment.
AB  - Extragastrointestinal stromal tumors (EGISTs) are rare tumors located outside the
      gastrointestinal tract. While curable resection is accepted as a noninvasive
      EGIST treatment, the therapeutic strategy for invasive EGISTs has not yet been
      established. The present report is the first to show a case of invasive EGIST
      completely resected after downsizing the tumor with imatinib treatment. A 69-year
      old female had multiple masses adjacent to the stomach and ileocecum. The primary
      lesion measured 18 cm in size and had invaded the stomach, pancreas and liver.
      The histological findings of fine-needle aspiration samples revealed a
      proliferation of dysplastic spindle cells that exhibited immunoreactivity for
      anti-c-kit antibodies. The masses were therefore diagnosed as multiple GISTs with
      invasion to other organs, with origin difficult to determine at the time.
      Nineteen months after the imatinib treatment, the tumors were downsized and
      distinct from the stomach, pancreas and liver. Accordingly, the tumors were
      regarded to be EGISTs derived from the mesentery. Because they slightly regressed
      26 months after treatment, surgery was applied to remove the EGISTs. The
      intraoperative findings showed no invasive signs, and the tumors were completely
      removed. The histological findings revealed the presence of dysplastic and c-kit
      positive spindle cells in the tumor with an MIB-I index of more than 5%,
      resulting in a final diagnosis of high-risk EGIST derived from the mesentery. No
      recurrence was detected for 16 months after resection. In conclusion,
      preoperative treatment with imatinib followed by curable resection is a feasible
      option to cure invasive EGISTs. 

PMID- 24078992
TI  - Effect of infliximab induction therapy on secondary systemic amyloidosis
      associated with Crohn's disease: case report and review of the literature.
AB  - Secondary systemic (AA) amyloidosis is reported as a serious complication that
      occurs in long-standing Crohn's disease (CD), with an incidence of 0.3-10.9%.
      Various therapeutic approaches using medicines and elemental diet have been
      recommended, but still there are no established standards of treatment for
      secondary systemic amyloidosis in CD. Only a few studies have shown the role of
      TNFalpha ihibitors in the treatment of AA amyloidosis over a long term period. We
      report the case of a 24-year-old male with CD complicated by AA amyloidosis with
      renal and gastrointestinal tract involvement treated with infliximab as induction
      therapy. Intestinal AA amyloidosis progression occurred at the same time with the
      development of CD as an early complication, whereas duration of CD prior to the
      diagnosis of renal AA amyloidosis was 6 years. Infliximab therapy (3 infusions)
      caused a significant decrease of serum amyloid A protein (by 97.9%), C-reactive
      protein (by 70%), improvement of disease activity index, and CD caused clinical
      symptoms. At the same time gradual progression of the renal damage (reduction of
      renal function) was not affected by the treatment. Direct efficacy of infliximab
      infusions on serum amyloid protein level may support the hypothesis of TNFalpha
      induced reduction on the progression of AA amyloidosis described in previous
      study reports. Targeted histological analysis of tissue biopsy is crucial to
      clarify the presence of AA amyloidosis in CD induced multiorgan damage cases. 

PMID- 24078993
TI  - Premalignant lesion of heterotopic pancreas combined with gastritis cystica
      profunda in gastric fundus.
AB  - Heterotopic pancreas, also known as ectopic pancreas, is found mainly in the
      stomach, duodenum, or jejunum. Pancreatic intraepithelial neoplasia (PanIN) is
      the non-invasive precursor of pancreatic cancer and gastritis cystica profunda
      (GCP) is considered a precursor of gastric cancer. As with most putative cancer
      precursor lesions, the diagnosis and treatment of these lesions has been
      controversial. A patient with no history of gastric surgery visited our
      institution for a regular evaluation. Endoscopy showed a 2 x 2 cm sized,
      protruding mass lesion with overlying normal mucosa on the fundus of stomach.
      Endoscopic ultrasound (EUS) and computed tomography (CT) led to the possible
      diagnosis of a gastrointestinal stromal tumor with cystic change. Laparoscopic
      gastric wedge resection was performed with intra-operative endoscopic guidance.
      Microscopic examination identified the mass as pancreatic tissue. Furthermore, it
      demonstrated PanIN, grade 3 (PanIN-3) mixed pancreatobiliary and intestinal type,
      arising in the heterotopic pancreas and associated with GCP. This report
      describes a rare case of a PanIN lesion combined with GCP as precursors of
      precancerous lesions in heterotopic pancreas and stomach. 

PMID- 24078994
TI  - Combined hepatocellular carcinoma - cholangiocarcinoma harboring a metastasis of
      colon adenocarcinoma.
AB  - Combined hepatocellular carcinoma-cholangiocarcinoma (cHCC-CC) represents a rare
      form of primary hepatic neoplasia. We report an unusual case of tumor-to-tumor
      metastasis: a cHCC-CC harboring a metastasis of colon adenocarcinoma developed in
      a 59 year old patient with alcohol-related liver cirrhosis. To the best of our
      knowledge, this is the first case of such a simultaneous occurrence. 

PMID- 24078995
TI  - Gastric heterotopic pancreas can be identified by endoscopic direct imaging with
      submucosal endoscopy.
AB  - Heterotopic pancreas (HP) is pancreatic tissue found outside the usual anatomical
      location of the pancreas, typically in the upper gastrointestinal tract.
      Asymptomatic HP is considered a benign submucosal tumor (SMT) that can be
      followed without intervention. However, invasive surgery or endoscopic resection
      is often inappropriately applied in cases of HP due to the difficulty of
      preoperative diagnosis by endoscopic ultrasonography (EUS) and tissue sampling
      error. Therefore, it is very important to distinguish HP from neoplastic SMTs,
      such as gastrointestinal stromal tumor (GIST), preoperatively. Herein, we
      describe two asymptomatic gastric HP cases that were distinguished by endoscopic
      direct imaging (EDI) on submucosal endoscopy with a mucosal flap method (SEMF).
      In the two patients, EUS-guided fine needle aspiration (FNA) biopsy failed to
      accurately diagnose two SMTs, consistent with the suspicion of a GIST on EUS.
      Accordingly, we attempted to perform bloc biopsy using SEMF as a novel method for
      obtaining tissue samples for two indefinite SMTs. Direct endoscopic imaging via a
      dissected submucosal tunnel revealed a yellowish, multi-nodular mass identified
      as pancreatic tissue. Histopathology of the bloc biopsy confirmed the diagnosis
      of HP. Our findings indicate that the characteristic EDI findings of gastric HP
      may distinguish these lesions from neoplastic SMTs. Additional evaluations of
      this approach are warranted. 

PMID- 24078996
TI  - Intracavitary applications of ultrasound contrast agents in
      hepatogastroenterology.
AB  - The era of the real time low mechanical index (MI) contrast enhanced ultrasound
      (CEUS) began in 2004. Since then, CEUS with second generation contrast agents
      like SonoVue has been able to offer a new clinical utility both in diagnosis and
      in interventional therapies. Intracavitary administration of SonoVue is an off
      label, extravascular application of CEUS. There are two distinct applications in
      gastroenterology that are currently emerging: contrast agent injection into
      physiological cavities and injection into non-physiological cavities and
      fistulas. Numerous reports on the extravascular or intracavitary administration
      of SonoVue have been published and the results are positive, even though larger
      prospective studies are still lacking. 

PMID- 24078997
TI  - Non-invasive alternative methods to hepatic venous pressure gradient measurement.

PMID- 24078998
TI  - Reply: To PMID 23539394.

PMID- 24078999
TI  - Porcelain gallbladder and cancer - an association to be revised.

PMID- 24079000
TI  - Celiac disease in older adults.

PMID- 24079001
TI  - "Standard of care" treatment for chronic viral C hepatitis in 2013 in Romania.

PMID- 24079002
TI  - Abdominal pain after minor trauma in a patient with Crohn's disease.

PMID- 24079003
TI  - Cardiac arrest after transjugular intrahepatic porto-systemic shunt creation in a
      28 year-old patient with end stage liver disease secondary to cystic fibrosis.

PMID- 24079005
TI  - A polycyclic borazine radical cation: [1,2-B2{1,2-(MeN)2C6H4}2](+).
AB  - The radical cation [1,2-B2{1,2-(MeN)2C6H4}2](+) has been synthesised and its
      structure and bonding have been probed using a combination of X-ray
      crystallography, EPR spectroscopy and DFT calculations which show that it
      represents a new type of radical centred primarily on two N-heterocyclic units
      joined by a B2 linker but with only a minor contribution from boron-based
      orbitals. 

PMID- 24079004
TI  - MOF-76: from a luminescent probe to highly efficient U(VI) sorption material.
AB  - MOF-76 exhibits not only high sensitivity for the detection of U(vi), but also
      high adsorption capacity of 298 mg g(-1) at a low pH value of ~3.0. Furthermore,
      the high selectivity for uranium adsorption over a series of competing metal ions
      is also illustrated. 

PMID- 24079006
TI  - Design, synthesis and evaluation of a boronic acid based artificial receptor for
      (L)-DOPA in aqueous media.
AB  - Design and synthesis of a boronic acid based artificial receptor which
      selectively and effectively bound to a neurotransmitter, l-DOPA (), in aqueous
      media. In addition, the synthetic receptor was found to effectively inhibit the
      DDC (l-DOPA decarboxylase) enzymatic reaction under physiological conditions. 

PMID- 24079007
TI  - Ni-Catalyzed [8+3] cycloaddition of tropones with 1,1-cyclopropanediesters.
AB  - A variety of cycloheptapyrane derivatives were prepared via Ni-catalyzed formal
      [8+3] cycloaddition of tropones with 1,1-cyclopropanediesters. The asymmetric
      version of the process can be achieved using either an enantiomerically enriched
      cyclopropane as the starting material or a racemic cyclopropane and a chiral
      Lewis acid. 

PMID- 24079008
TI  - Paper-based photoelectrochemical immunosensing based on CdS QD sensitized
      multidimensional porous ZnO spheres promoted by carbon nanotubes.
AB  - An ultrasensitive photoelectrochemical (PEC) immunoassay was introduced into
      microfluidic paper-based analytical devices (MU-PADs) based on a multiple
      electron transfer system for the first time, which was constructed using narrow
      band-gap semiconductor nanoparticles (NPs), wide-band-gap semiconductor NPs, and
      an electron-accepting medium. 

PMID- 24079009
TI  - Synthesis of sequence controlled acrylate oligomers via consecutive RAFT monomer
      additions.
AB  - An effective procedure to synthesize sequence controlled oligoacrylates with up
      to four monomer insertions via the RAFT technique is presented. Two different
      sets of oligomers with a preferred monomer order were synthesized. Recycling SEC
      allowed for facile and automated purification of the monodisperse sequence
      controlled materials. 

PMID- 24079010
TI  - Synthesis, photophysical properties, and excited state dynamics of a platinum
      complex of tetracene imide disulfide.
AB  - A platinum complex containing a tetracene dicarboxylic imide disulfide (TIDS) was
      synthesized and structurally characterized by X-ray analysis. Steady-state
      absorption and emission spectroscopy for Pt-TIDS revealed its extended pi
      conjugated structure. Excited state studies characterized its triplet state with
      a lifetime of 0.18-0.28 MUs. 

PMID- 24079012
TI  - Crystal structure and morphology control of molybdenum carbide nanomaterials
      synthesized from an amine-metal oxide composite.
AB  - Multiple phases of molybdenum carbide have been synthesized using a unique amine
      metal oxide composite material. By combining molybdenum oxide and an amine, a
      templated precursor is formed which can be thermally decomposed to form
      molybdenum carbide with control over the structure and morphology of the nano
      sized products. 

PMID- 24079011
TI  - Rescuing recombinant proteins by sequestration into the P22 VLP.
AB  - Here we report the use of a self-assembling protein cage to sequester and
      solubilize recombinant proteins which are usually trafficked to insoluble
      inclusion bodies. Our results suggest that protein cages can be used as novel
      vehicles to rescue and produce soluble proteins that are otherwise difficult to
      obtain using conventional methods. 

PMID- 24079013
TI  - A reduced dimensionality quantum mechanical study of the H + HCF3 <-> H2 + CF3
      reaction.
AB  - Recently, the authors developed a new method to construct a two-dimensional
      potential energy surface (PES) for use in reduced-dimensionality quantum
      scattering calculations in chemical reactions. In this approach the minimum
      energy path of a reaction was utilized and the rest of the surface was fitted by
      a Morse function. Here we test this method on the H + HCF3 <-> H2 + CF3 reaction.
      The geometry optimizations and frequency calculations are done at the MP2/cc-pVTZ
      level of theory, while the energies are calculated at the CCSD(T)/aug-cc-pVTZ
      level. An adiabatic energy barrier of 59.61 kJ mol(-1) for the forward direction
      is suggested by our calculations, and the reaction is endothermic by 10.55 kJ
      mol(-1) in the same direction. When compared to classical transition state
      theory, quantum scattering calculations suggest that a tunnelling effect can be
      observed in both forward and backward reactions. For the forward direction, the
      quantum tunnelling is important at temperatures typically lower than 300 K. It
      has a greater contribution to the backward reaction, and is over a wider
      temperature range from 200 K to 1000 K. We also conducted an analysis of the
      kinetic isotope effects on the backward reaction by replacing H2 with D2. These
      results also clearly demonstrate the significance of quantum tunnelling in the
      reaction. 

PMID- 24079014
TI  - A myeloproliferative neoplasm with translocation t(8;9)(p22;p24) involving JAK2
      gene.

PMID- 24079015
TI  - Invasive mucormycosis without radiological alterations.

PMID- 24079016
TI  - Hopes and fears for future of coral reefs.
AB  - Coral reefs are widely recognised as vital yet highly vulnerable
      ecosystems.Recent studies have demonstrated the possibility of recovery after
      disturbance,but also the continuing threats and decline. Michael Gross reports.

PMID- 24079017
TI  - Bill Bement.

PMID- 24079018
TI  - Guest editorial: Advanced algorithms of bioinformatics.

PMID- 24079019
TI  - Guest editors' Introduction to the special section on computational methods in
      systems biology.

PMID- 24079020
TI  - Reply to A. Berti et al.

PMID- 24079021
TI  - Reply to K. Devisetty et al.

PMID- 24079022
TI  - [Confusion about morel mushrooms!].

PMID- 24079023
TI  - [The man before the treatment].

PMID- 24079025
TI  - Growing up virtual.

PMID- 24079024
TI  - Scientists. Curiosity and observation.

PMID- 24079026
TI  - Trans-Atlantic debate: whether level I evidence comparing thoracic endovascular
      repair and medical management is necessary for uncomplicated type B aortic
      dissections.

PMID- 24079028
TI  - A troubled state. Part 3. What can we learn from Iowa's experience?

PMID- 24079027
TI  - Trans-Atlantic debate: whether level I evidence comparing thoracic endovascular
      repair and medical management is necessary for uncomplicated type B aortic
      dissections.

PMID- 24079029
TI  - [One case report of pharyngeal bursa invasive fungal disease with lower cranial
      nerve involvement as the first manifestation].
AB  - To increase the identification of pharyngeal bursa invasive fungal disease with
      lower cranial nerve involvement, reduce the misdiagnosis and improve the
      awareness of invasive fungal disease. We report the clinical data of a case with
      lower cranial nerve involvement as the first manifestation and reviewed the
      related literature.

PMID- 24079030
TI  - Editor's note.

PMID- 24079031
TI  - [A case report of acute severe methamidophos poisoning associated with drowning].

PMID- 24079032
TI  - [Structural equation model analysis of risk factors for low back pain among
      greenhouse vegetable-planting farmers].
AB  - OBJECTIVE: To explore the risk factors of low back pain (LBP) among greenhouse
      vegetable planting farmers and estimate the level of the effects. METHODS: A self
      made questionnaire based on the Dutch Musculoskeletal Questionnaire and the
      Nordic Questionnaire was conducted to 639 greenhouse vegetable planting farmers
      and then structural equation model was used to analyze the risk factors of LBP in
      SmartPLS software. RESULTS: The coefficient of determination of the model was
      0.827, and the structural coefficients of dynamic loads, static loads, force
      exertion, ergonomic environment and repetitive loads on LBP were 0.21, 0.43,0.27,
      0.045 and 0.034 respectively, and the total effects of the above latent variables
      on LBP were 0.21, 0.43,0.27, 0.33 and 0.034 respectively. CONCLUSION: The main
      risk factors of LBP among greenhouse vegetable planting farmers were static
      loads, ergonomic environment, force exertion and dynamic loads.

PMID- 24079033
TI  - [Acute toluene or xylene poisoning case analysis of domestic journals].

PMID- 24079034
TI  - [Assessment comparison between area sampling and personal sampling noise
      measurement in new thermal power plant].
AB  - OBJECTIVE: To compare the results of noise hazard evaluations based on area
      sampling and personal sampling in a new thermal power plant and to analyze the
      similarities and differences between the two measurement methods. METHODS:
      According to Measurement of Physical agents in Workplace Part 8: Noise(GBZff
      189.8-2007), area sampling was performed at various operating points for noise
      measurement, and meanwhile the workers under different types of work wore noise
      dosimeters for personal noise exposure measurement. The two measurement methods
      were used to evaluate the level of noise hazards in the enterprise according to
      the corresponding occupational health standards, and the evaluation results were
      compared. RESULTS: Area sampling was performed at 99 operating points, the mean
      noise level was 88.9 +/- 11.1 dB (A)(range, 51.3-107.0 dB (A)), with an over
      standard rate of 75.8%. Personal sampling was performed (73 person times),and the
      mean noise level was 79.3 +/- 6.3 dB (A), with an over-standard rate of 6.6% (
      16/241 ). There was a statistically significant difference in the over-standard
      rate between the evaluation results of the two measurement methods ( x2=53.869,
      ?<0.001 ). CONCLUSION: Because of the characteristics of the work in new thermal
      power plants, the noise hazard evaluation based on area sampling cannot be used
      instead of personal noise exposure measurement among workers. Personal sampling
      should be used in the noise measurement in new thermal power plant.

PMID- 24079035
TI  - [The prevalence and influencing factors of eye diseases for IT industry video
      operation workers].
AB  - OBJECTIVE: To investigate the situation of video-contact and eye diseases for IT
      industry video operation workers, and to analyze the influencing factors,
      providing scientific evidence for the make of health-strategy for IT industry
      video operation workers. METHODS: We take the random cluster sampling method to
      choose 190 IT industry video operation workers in a city of Jiangsu province,
      analyzing the relations between video contact and eye diseases. RESULTS: The
      daily video contact time of IT industry video operation workers is 6.0-16.0
      hours, whose mean value is (I 0.1 +/- 1.8) hours. 79.5% of workers in this survey
      wear myopic lens, 35.8% of workers have a rest during their working, and 14.2% of
      IT workers use protective products when they feel unwell of their eyes. Following
      the BUT experiment, 54.7% of IT workers have the normal examine results of
      hinoculus, while 45.3% have the abnormal results of at least one eye.
      Simultaneously, 54.7% workers have the normal examine results of hinoculus in the
      SIT experiment, however, 42.1% workers are abnormal. According to the broad
      linear model, there are six influencing factors (daily mean time to video,
      distance between eye and displayer, the frequency of rest, whether to use
      protective products when they feel unwell of their eyes, the type of dis player
      and daily time watching TV.) have significant influence on vision, having
      statistical significance. At the same time, there are also six influencing
      factors (whether have a rest regularly,sex, the situation of diaphaneity for
      cornea, the shape of pupil, family history and whether to use protective products
      when they feel unwell of their eyes.) have significant influence on the results
      of BUT experiment,having statistical significance. However, there are seven
      influencing factors (the type of computer, sex, the shape of pupil, the situation
      of diaphaneity for cornea, the angle between displayer and workers' sight, the
      type of displayer and the height of operating floor.) have significant influence
      on the results of SIT experiment,having statistical significance. CONCLUSIONS:
      The health-situation of IT industry video operation workers' eye is not
      optimistic, most of workers are lack of protection awareness; we need to
      strengthen propaganda and education according to its influencing factors and to
      improve the level of medical control and prevention for eye diseases in relevant
      industries.

PMID- 24079036
TI  - [Study on the metabolism of toluene diisocyanate in urine of rats and its dose
      effect relationship].

PMID- 24079037
TI  - [Therapeutic efficacy of salbutamol and dexamethasone added into whole lung
      lavage fluid in patients with pneumoconiosis].
AB  - OBJECTIVE: To investigate the therapeutic efficacy and safety of salbutamol and
      dexamethasone added into large-volume whole lung lavage (WLL) fluid in patients
      with pneumoconiosis. METHODS: A total of 176 patients with pneumoconiosis were
      randomly divided into control group (n=86) and treatment group (n=90). The
      control group received WLL with 0.9% sodium chloride solution, while for the
      treatment group, salbutamol and dexamethasone were added into the WLL fluid for
      both lungs at the 1st and 4th WLLs.Before and after WLL, the pulmonary wheezing,
      arterial partial pressure of oxygen (Pa02), peak airway pressure(Pa peak), amount
      of intrapulmonary residual fluid, forced expiratory volume in one second (FEVw)
      (72 h later),diffusion capacity for carbon monoxide (DLCO ), and forced vital
      capacity (FVC) were measured for comparison between the two groups. RESULTS:
      After WLL, the treatment group had a significantly lower detection rate of
      pulmonary wheezing than the control group ( 13.3% vs 29.1 %, x2=5.028, ?=0.025),
      and the control group had a significantly higher incidence rate of pulmonary
      wheezing than the treatment group (21.8% vs 3.7%, 0R=5.423,95%CI 2.036-9.568 ).
      Compared with the control group, the treatment group had significantly higher
      Pa02 and significantly lower Pa peak and amount of intrapulmonary residual fluid
      (t =2.163 -4.132, P<0.05) and significantly higher FEV1, DLCO, and FVC (t=1.986
      2.345, P<0.05) after WLL. CONCLUSION: Salbutamol and dexamethasone added into
      large-volume WLL fluid may effectively alleviate bronchial spasm, reduce
      hypoxemia, and decrease Pa peak in patients with pneumoconiosis, thus promoting
      lung function recovery after WLL.

PMID- 24079038
TI  - [Observation on the effects of the treatment of sillicosis merger asthma].
AB  - OBJECTIVE: To investigate Salmeterol/Fluticasone Propionate and Totropiumi
      treatment of Sillicosis merger Asthma. METHODS: 30 patients with Sillicosis
      merger Asthma were randomly divided into group Salmeterol/Fluticasone Propionate(
      Single group) ( n=14) and group Salmeterol/Fluticasone Propionate and Totropiumi
      (Joint group) ( n= 16), patient in single group were only given
      Salmeterol/Fluticasone Propionate (50 f.Lg Bid) inhaling,and those in Joint group
      were given Salmeterol/Fluticasone Propionate (50 f.Lg Bid) and Totropiumi ( 18
      f.Lg Qd) inhaling. The treatment was last for 6 months.Before the
      treatment,evaluation of the two groups of Sillicosis installment,determination
      their foungation lung function and ACT score .. After the cause of treatment,
      lung function FEV10/FVC(% ), FEV10 pred%, FEV10(ml), ACT score, the incidence of
      side effects of two groups were compared and analyzed. RESULT: The two groups
      before the treatment of lung fuction and ACT score had no statistically
      significant difference. The two groups after treatment of lung fuction FEV10/FVC
      (% ),FEV10 pred%, ACT score obviously higher than before treatment (P<0.05),
      Joint group in FEV1/FVC(% ), ACT score significantly higher than in Single group
      (?<0.05), Joint group acute attack times(0.98+/-0.79)/time lower than Single
      group (2.10 +/- 0.81 )/time (t=3.86,P<0.05). There were no significant side
      effect in two groups. CONCLUSION: Salmeterol/Fluticasone Propionate or the
      combination of Salmeterol/Fluticasone Propionate and Totropiumi can improve lung
      function and clinical symptoms of patients with Sillicosis merger Asthma. It is
      also better that the combination of Salmeterol/Fluticasone Propionate and
      Totropiumi obviously improve clinical symptoms of patients and reduice acute
      attack times.

PMID- 24079039
TI  - [Effect of treatment with early blood purification combined with prednisone and
      cyclophosphamide for patients with acute paraquat poisoning].

PMID- 24079040
TI  - [Clinical analysis of 16 cases children paraquat poisoning].

PMID- 24079041
TI  - [The clinical characteristics of eight cases of acute epoxyethane poisoning].

PMID- 24079042
TI  - [Mercury poisoning presenting with erythromelaigia: a case report].

PMID- 24079043
TI  - [Hormonotherapy for treating femoral head necrosis induced by paraquat poisoning:
      a report of 2 cases].

PMID- 24079044
TI  - [Focal issues in treating acute poisoning by paraquate].

PMID- 24079045
TI  - [Pulmonary fibrosis and micro RNA].

PMID- 24079046
TI  - Reply of author.

PMID- 24079047
TI  - Left ventricular puncture after intercostal catheter insertion.

PMID- 24079048
TI  - [Q & A. Intestinal obstruction without history of laparotomy].

PMID- 24079049
TI  - 80 x 20: A call to action for Alabama nurses from the National Institute of
      Medicine (part 1).

PMID- 24079050
TI  - Healthwise RN: mindful health.

PMID- 24079051
TI  - Important provisions of Act 766 of 2013 (Arkansas Peer Review Fairness Act).

PMID- 24079052
TI  - The sleep sack innovation.

PMID- 24079053
TI  - G Richard Smith, MD: an experienced leader at Helm at the UAMS College of
      Medicine.

PMID- 24079054
TI  - Rabies post-exposure prophylaxis.

PMID- 24079055
TI  - Pancytopenia and lactic acidosis associated with linezolid use in a patient with
      empyema.
AB  - OBJECTIVE: To describe a patient who developed pancytopenia and lactic acidosis
      after receiving linezolid therapy. CASE SUMMARY: A 32-year-old man with past
      medical history of heart failure, hypertension received a 14-day course of
      linezolid for treatment of empyema with broncho-pleural fistula. During his
      follow up visit, he was found to be septic and further evaluation showed
      pancytopenia, acidosis and elevated liver enzymes. With the exclusion of other
      possible etiologies, the time course to development of these laboratory
      abnormalities correlated with the use of linezolid. Antibiotics were switched
      subsequently and the labs improved after reaching a nadir on the fourth day after
      stopping linezolid. DISCUSSION: Linezolid was noted to cause time and dose
      dependent reversible myelosuppression in preclinical studies. There are several
      case reports of throinbocytopenia occurring with linezolid use, but only few
      cases of pancytopenia and lactic acidosis are reported. Exact mechanism of
      toxicity is unknown, but many hypothesize it to be similar to chloramphenicol
      marrow toxicity because of the cross-reactivity to mitochondrial ribosomes.
      CONCLUSIONS: Clinicians should be aware of linezolid as a drug capable of causing
      pancytopenia, lactic acidosis and elevated liver enzymes. While recovery is
      usually complete following withdrawal of the drug, we need to still monitor for
      these rare but severe complications; and consider treating only for a shorter
      duration, if possible.

PMID- 24079056
TI  - Progressive kidney failure as the sole manifestation of extrapulmonary
      sarcoidosis.
AB  - Sarcoidosis is a chronic multisystem disorder characterized by an accumulation of
      T lymphocytes and mononuclear phagocytes, non-caseating epitheliod granulomas and
      derangement of normal tissue architecture in affected organs. Sarcoidosis can
      affect any organ system, however approximately 90% of patients with sarcoidosis
      have pulmonary, lymph node, cutaneous or ocular manifestations. Renal involvement
      in sarcoidosis is rare and clinically significant renal dysfunction even less
      common. We present a case of isolated renal sarcoidosis which manifested with
      progressively worsening renal function and hypercalcemia. A systematic diagnostic
      approach with pertinent laboratory studies, imaging and renal biopsy elucidated
      the diagnosis of renal sarcoidosis without any evidence of systemic involvement.

PMID- 24079057
TI  - Kitchen surgery and house calls in old Fort Smith.
AB  - Medical practice in the late nineteenth and early twentieth centuries consisted
      largely of kitchen surgery and house calls. The practices of Dr. St. Cloud Cooper
      and other Fort Smith doctors reflected the standards of practice in Arkansas and
      the nation as the principles of aseptic surgery gradually gained acceptance. The
      doctor's black bag used on house calls still lacked the effective agents which
      became available during the mid-twentieth century, leaving the physician to rely
      on personal inner resources in order to perform a useful service.

PMID- 24079058
TI  - Trans-catheter aortic valve implantation for non-classical indications.
AB  - BACKGROUND: Trans-catheter aortic valve implantation (TAVI) has emerged as a
      novel therapeutic approach for patients with severe tricuspid aortic stenosis
      (AS) not suitable for aortic valve replacement. OBJECTIVES: To describe our
      initial single-center experience with TAVI in patients with "off-label"
      indications. METHODS: Between August 2008 and December 2011 we performed TAVI in
      186 patients using trans-femoral, transaxillary, trans-apical and trans-aortic
      approaches. In 11 patients (5.9%) TAVL was undertaken due to: a) pure severe
      aortic regurgitation (AR) (n = 2), b) prosthetic aortic valve (AV) failure (n =
      5), c) bicuspid AV stenosis (n = 2), and d) prosthetic valve severe mitral
      regurgitation (MR) (n = 2). RESULTS: Implantation was successful in all: six
      patients received a CoreValve and five patients an Edwards-Sapien valve. In
      hospital mortality was 0%. Valve hemodynamics and function were excellent in all
      patients except for one who received an Edwards-Sapien that was inside a
      Mitroflow prosthetic AV and led to consistently high trans-aortic gradients. No
      significant residual regurgitation in AR and MR cases was observed. CONCLUSIONS:
      TAVI is a good alternative to surgical AV replacement in high risk or inoperable
      patients with severe AS. TAVI for non-classical indications such as pure AR,
      bicuspid AV, and failed prosthetic aortic and mitral valves is feasible and safe
      and may be considered in selected patients.

PMID- 24079059
TI  - Newborn screening for severe T and B cell immunodeficiency in Israel: a pilot
      study.
AB  - BACKGROUND: Enumeration of T cell receptor excision circles (TREC) was recently
      adopted as a neonatal screening assay for severe combined immunodeficiency
      (SCID). Enumeration of kappa-deleting recombination excision circle (KREC) copy
      numbers can be similarly used for early assessment of B cell lymphopenia.
      OBJECTIVE: To assess the ability of TREC and KREC counts to identify patients
      with combined T and B cell immunodeficiency in a pilot study in Israel. METHODS:
      We studied seven children born in Israel during the years 2010-2011 and later
      diagnosed with SCID, and an additional patient with pure B cell immunodeficiency.
      TREC and KREC in peripheral blood upon diagnosis and in their neonatal Guthrie
      cards were analyzed using real-time quantitative polymerase chain reaction, as
      were Guthrie cards with dried blood spots from healthy newborns and from normal
      and SCID-like controls. RESULTS: The first features suggestive of SCID presented
      at age 3.1 +/- 2.4 months in all patients. Yet, the diagnosis was made 4.1 +/-
      2.9 months later. Their TREC were undetectable or significantly low at their
      clinical diagnosis and in their originally stored Guthrie cards, irrespective of
      the amount of their circulating T cells. KREC were undetectable in six SCID
      patients who displayed B cell lymphopenia in addition to T cell lymphopenia. KREC
      were also undetectable in one patient with pure B cell immunodeficiency.
      CONCLUSIONS: TREC and KREC quantification are useful screening tests for severe T
      and B cell immunodeficiency. Implementation of these tests is highly important
      especially in countries such as Israel where a high frequency of consanguinity is
      known to exist.

PMID- 24079060
TI  - "General deterioration": a diagnosis that is a marker for risk of mortality upon
      re-admission.
AB  - BACKGROUND: Predicting mortality is important in treatment planning and
      professional duty towards patients and their families. OBJECTIVES: To evaluate
      the predictive value regarding patients' survival once the diagnosis of "general
      deterioration" replaces an ICD-9 diagnosis upon re-admission. METHODS: In this
      retrospective cohort case-control study, we screened the records of patients re
      admitted at least three times during the past 2 years. For each patient's death
      during the third hospitalization, we matched (for age and gender) a patient who
      survived the third hospitalization. We evaluated 14 parameters potentially
      accountable for increased risk of mortality, e.g., length of stay at each
      admission, interval to re-admission, etc. We applied a multifactorial analysis
      using logistic regression to predict the risk of mortality during the third
      hospitalization as potentially affected by the aforementioned parameters.
      RESULTS: The study included 81 study patients and 81 controls. Of the 14
      parameters potentially explaining an increased risk of mortality during the third
      hospitalization, several were found to be statistically significant. The most
      significant was the diagnostic switch from a specific ICD-9 diagnosis on first
      admission to the non-specific diagnosis of "general deterioration" at the second
      hospitalization. In such cases, the risk of death during the third
      hospitalization was increased by 5300% (odds ratio = 54, P = 0.008). The
      increased risk of mortality was not restricted to patients with malignancy as
      their background diagnosis. CONCLUSIONS: At re-admission a switch from disease
      specific diagnosis to the obscure diagnosis "general deterioration" increases the
      subsequent risk of mortality.

PMID- 24079061
TI  - Health services utilization under Qassam rocket attacks.
AB  - BACKGROUND: The Qassam rocket attacks on southern Israel during the years 2000
      2007 created a unique situation of life undera continuous threat. The effect of
      this unique situation on health services utilization has not been previously
      examined. OBJECTIVES: To evaluate health utilization patterns in two primary care
      clinics in southern Israel: one under continuous attacks of Qassam rockets as
      compared with a similar clinic not under a rocket threat. METHODS: We conducted a
      retrospective cross-sectional study in two primary care clinics in southern
      Israel, with 11,630 persons listed in the two clinics during the entire study
      period. The primary outcome measures were total annual number of visits per
      person to the clinic and for specific diagnoses, and the number of drug
      prescriptions issued, emergency room (ER) visits, hospitalization days, cardiac
      catheterizations and coronary bypass surgeries. RESULTS: In both clinics there
      was an increase over time in the mean annual number of visits per person. During
      the years of severe attacks there was an increase in visits with a chief
      complaint of depression and anxiety and an increase in the number of anxiolytic
      prescriptions in the study clinic compared with the control. During the same
      period there was a decrease in the number of ER visits in the study clinic
      compared with the control. CONCLUSIONS: The population under continuous life
      threatening events showed more depression and anxiety problems. Under severe
      bombardment, the residents prefer not to leave home, unless necessary.

PMID- 24079062
TI  - Double-blind placebo and active (caffeine) controlled study to examine the
      effects of the herbal nutritional supplement beverage "Wake up" on vigilance and
      function after lunch.
AB  - BACKGROUND: Post-lunch dip is a well-known phenomenon that results in a
      substantial deterioration in function and productivity after lunch. OBJECTIVES:
      To assess whether a new herbal-based potentially wake-promoting beverage is
      effective in counteracting somnolence and reduced post-lunch performance.
      METHODS: Thirty healthy volunteers were studied on three different days at the
      sleep clinic. On each visit they ate a standard lunch at noontime, followed by a
      drink of "Wake up," 50 mg caffeine, or a placebo in a cross-over double-blind
      regimen. At 30 and 120 minutes post-drinking, they underwent a battery of tests
      to determine the effects of the beverage. These included: a) a subjective
      assessment of alertness and performance based on a visual analog scale, and b)
      objective function tests: the immediate word recall test, the digit symbol
      substitution test (DSST), and hemodynamic measurements. The results of the three
      visits were compared using one-way analysis of variance, with P < 0.05 considered
      statistically significant. RESULTS: In all performance tests, subjective
      vigilance and effectiveness assessment, both Wake up and caffeine were
      significantly superior to placebo 30 minutes after lunch. However, at 2 hours
      after lunch, performance had deteriorated in those who drank the caffeine
      containing drink, while Wake up was superior to both caffeine and placebo. Blood
      pressure and pulse were higher 2 hours after caffeine ingestion, compared to both
      Wake up and placebo. CONCLUSIONS: These results suggest that a single dose of
      Wake up is effective in counteracting the somnolence and reduced performance
      during the post-lunch hours. In the current study it had no adverse hemodynamic
      consequences.

PMID- 24079063
TI  - Psychiatric consultation of all suicide-attempt patients during a one year period
      in a tertiary hospital.
AB  - BACKGROUND: Many tertiary hospitals provide psychiatric services that treat
      diverse clinical situations. Most patients referred to these services following a
      serious suicide attempt have psychiatric diagnoses, but their unique
      characteristics and needs are not known. OBJECTIVES: To examine the files of
      patients hospitalized in a tertiary hospital in Israel following a serious
      suicide attempt. Their mental conditions were determined and their unique
      demographic and clinical characteristics and needs compared to the other patients
      examined by the psychiatric service. METHODS: The study focused on 49 consecutive
      patients admitted after performing a life-threatening suicide attempt. They were
      compared to 389 non-suicidal patients assessed by the same psychiatric service
      during one year. RESULTS: Nearly half the patients hospitalized following a
      serious suicide attempt had only an axis II diagnosis (personality disorder). Non
      violent methods of suicide were used predominantly by females, and violent
      methods mainly by males. All suicide attempts by Muslims used violent methods,
      while less than half the attempts by Jews were violent. Compared to the non
      suicidal patients, the suicide-attempters group was younger and had greater
      representation of Jewish females and Muslim males. Compared to the non-suicidal
      patients, these patients required more intense psychiatric care, earlier
      commencement of treatment in the course of hospitalization, more psychiatric
      visits and treatment hours, and more referrals for further care. Several risk
      factors appear to be associated with a need for more intense in-hospital care and
      a greater need for referral: male gender, religion, method of suicide attempt
      (violent vs. non-violent), and the existence of a psychiatric diagnosis.
      CONCLUSIONS: Suicide-attempt patients who are in need of hospitalization for
      further medical treatment have unique clinical characteristics and require more
      intense treatment provided by the Consultation-Liaison Unit.

PMID- 24079064
TI  - Cricopharyngeal achalasia in children: surgical and medical treatment.
AB  - BACKGROUND: Cricopharyngeal achalasia (CA) is a rare cause of dysphagia in
      children presenting with non-specific symptoms such as choking, food
      regurgitation, nasal reflux, coughing, recurrent pneumonia, cyanosis, and failure
      to thrive. It results from failure of relaxation of the upper esophageal
      sphincter (UES) and may appea reither as an isolated lesion or in conjunction
      with other pathologies. Recognition and early diagnosis of this condition may
      minimize morbidity in children. OBJECTIVES: To evaluate the clinical course of
      four children with cricopharyngeal achalasia presenting to our clinic. METHODS:
      We conducted a 5 year retrospective chart review in a tertiary referral center.
      RESULTS: Four children were diagnosed with primary cricopharyngeal achalasia
      between 2006 and 2010. Diagnosis was established by videofluoroscopy and all
      underwent uneventful cricopharyngeal myotomy. Three children recovered completely
      and one child showed partial improvement. For residual UES spasm in a partially
      improved patient, botulinum toxin was injected into the UES which led to further
      improvement. Dysphagia recurred in one child who was successfully treated with
      botulinum toxin injection. CONCLUSIONS: Cricopharyngeal myotomy is a safe
      procedure in infants and young children. Botulinum toxin injection of the UES was
      found to be effective in refractory cases.

PMID- 24079065
TI  - Placebo for a single night improves sleep in patients with objective insomnia.
AB  - BACKGROUND: Insomnia is the most common sleep disorder. Treatment options are
      improved sleep hygiene, relaxation, cognitive behavioral therapy, and
      medications. Studies examining the effect of hypnotics on insomnia reported that
      placebo had a substantial beneficial effect. OBJECTIVES: To evaluate whether
      placebo is an effective treatment for insomnia. METHODS: We assessed 25 patients
      with insomnia who were enrolled in a hypnotic study but prior to the study were
      asked to undergo two full nights in laboratory polysomnography studies: with and
      without a placebo. Although they were not explicitly told that they were
      receiving a placebo, the participants knew that the results of these studies
      would determine whether they met the criteria to participate in the
      pharmaceutical study. RESULTS: Although the participants acknowledged that they
      were given a placebo, almost all measures of their sleep improved. With placebo,
      sleep latency was shortened from 55.8 +/- 43.5 to 39.8 +/- 58.5 minutes (P <
      0.05); total sleep time was extended from 283 +/- 72.5 to 362.9 +/- 56.3 minutes,
      and sleep efficiency improved from 59.57 +/- 14.78 to 75.5 +/- 11.70% (P < 0.05).
      Interestingly, placebo had no effect on the relative sleep stage distribution
      (percentage of total sleep time), except for a trend toward increased percentage
      of REM sleep. CONCLUSIONS: Our findings show a clear and significant beneficial
      effect of placebo on insomnia, despite participants' understanding that they were
      receiving placebo. These results emphasize the importance of the patients'
      perception and belief in insomnia treatment, and suggest that in some cases
      placebo may serve as a treatment.

PMID- 24079066
TI  - Aortic valve-sparing surgery in Marfan syndrome.
AB  - BACKGROUND: Patients with Marfan syndrome are referred for cardiac surgery due to
      root aneurysm with or without aortic valve regurgitation. Because these patients
      are young and frequently present with normal-appearing aortic cusps, valve
      sparing is often recommended. However, due to the genetic nature of the disease,
      the durability of such surgery remains uncertain. METHODS: Between February 2004
      and June 2012, 100 patients in our department suffering from aortic aneurysm with
      aortic valve regurgitation underwent elective aortic valve-sparing surgery. Of
      them, 30 had Marfan syndrome, were significantly younger (30 +/- 13 vs. 53 +/- 16
      years), and had a higher percentage of root aneurysm, compared with ascending
      aorta aneurysm in their non-Marfan counterparts. We evaluated the safety,
      durability, clinical and echocardiographic mid-term results of these patients.
      RESULTS: While no early deaths were reported in either group, there were a few
      major early complications in both groups. At follow-up (reaching 8 years with a
      mean of 34 +/- 26 months) there were no late deaths, and few major late
      complications in the Marfan group. Altogether, 96% and 78% of the patients were
      in New York Heart Association functional class I-II in the Marfan and non-Marfan
      groups respectively. None of the Marfan patients needed reoperation on the aortic
      valve. Freedom from recurrent aortic valve regurgitation > 3+ was 94% in the
      Marfan patients. CONCLUSIONS: Aortic valve-sparing surgery in Marfan symdrome
      patients is safe and yields good mid-term clinical outcomes.

PMID- 24079067
TI  - The "off-label" TAVI.

PMID- 24079068
TI  - A drop of prevention is worth a liter of cure: the case for newborn screening for
      severe T cell immune deficiency in Israel.

PMID- 24079069
TI  - Atypical femoral fractures and their relation to bisphosphonate use.

PMID- 24079070
TI  - Laryngeal edema, rhabdomyolysis and acute renal failure following ingestion of
      "black rock".

PMID- 24079071
TI  - Life-threatening oropharyngeal aphagia as the major manifestation of
      dermatomyositis.

PMID- 24079072
TI  - Electrical burn with abdominal visceral involvement managed by immediate
      aggressive debridement and flap coverage.

PMID- 24079073
TI  - Atypical presentation of Kaposi's sarcoma in an HIV-infected patient.

PMID- 24079074
TI  - Receptors of thyroid hormones.
AB  - The important physiological actions of the thyroid hormones are mediated by
      binding to nuclear thyroid hormone receptors (TRs), encoded by two genes TRalpha
      and TRbeta. These receptors act as hormone-dependent transcription factors by
      binding to DNA motifs located in the regulatory regions of target genes and
      recruiting coregulators (coactivators and corepresors), which alter chromatin
      structure. Novel thyromimetics have been developed that bind preferentially
      TRbeta could be used for treatment of hyperlipidemia and obesity. TRbeta gene
      mutations cause resistance to thyroid hormones (RTH), characterized by
      inappropriately high thyroid-stimulating hormone (TSH) levels due to lack of
      feedback inhibition of thyroid hormones on the hypothalamus and pituitary gland,
      and to reduced sensitivity of other TRbeta target tissues to thyroid hormones.
      Very recently, patients heterozygous for TRalpha mutations have been identified.
      These patients exhibit clinical symptoms of hypothyroidism in TRalpha target
      tissues such as intestine or hearth and near normal circulating TSH and thyroid
      hormone levels.

PMID- 24079075
TI  - Circulating non-coding RNAs as biomarkers of beta cell death in diabetes.
AB  - Death of pancreatic islet beta cells is a common feature of type 1 and 2 diabetes
      and often follows islet cell transplantation. Measurement of blood glucose is
      currently the only blunt instrument available to diagnose diabetes mellitus, and
      we lack tools to quantify islet cell loss or protection thereof. A class of RNA
      molecules (called microRNAs/miRNAs/miRs) that regulate endogenous gene expression
      via mRNA cleavage or translational arrest have been identified to be critical for
      birth, maintenance and regeneration of pancreatic beta cells. Recent
      demonstration that microRNAs can potentially be utilised as biomarkers due to
      their serum stability, has triggered increasing interest in understanding their
      role as regulators or biomarkers of disease. This review aims to delve into the
      potential of miRNA biomarkers, and whether miRNA profiles are indicators or
      effector of disease pathology. Furthermore, an outline for identifying and
      confirming islet-specific miRNA biomarkers is discussed.

PMID- 24079077
TI  - Adiponectin levels in south Indian children with type 1 diabetes mellitus and
      nondiabetic children and its correlation with anthropometry and glycemic control.
AB  - Studies have reported high adiponectin levels in children with type 1 diabetes
      mellitus (T1DM). Adiponectin has been found to have anti-atherogenic action and
      other protective functions. We wanted to estimate adiponectin level in south
      Indian T1DM children and compare it with that of non-diabetic children and study
      its correlation with anthropometry and glycemic status. Sixty children with T1DM
      and forty non-diabetic children of age less than 15 years were analysed. Mean
      adiponectin level was higher in T1DM group than in non diabetic group (p < 0.001)
      irrespective of the age group or sex. Negative correlation was observed between
      SFT- triceps and adiponectin in diabetic and control group. Multiple regression
      coefficient analysis of various parameters showed SFT- triceps as a statistically
      significant predictor of adiponectin level (p = 0.001). We conclude that,
      children with T1DM had higher adiponectin level than non-diabetic children. Low
      SFT- triceps measuremet may be a predictor of higher adiponectin level.

PMID- 24079078
TI  - Klinefelter syndrome and cancer: from childhood to adulthood.
AB  - The classic clinical manifestations of Klinefelter syndrome (KS) are expressions
      of the primary hypogonadism that causes severe alterations of the reproductive
      and endocrine functions of the testis. It is a syndrome that causes infertility,
      and in addition leads to multiple disorders that involve a variety of tissues and
      organs. Important medical conditions associated with KS are categorized as: 1)
      motor, cognitive, and behavioral dysfunction; 2) tumors; 3) vascular disease and
      4) endocrine/ metabolic and autoimmune diseases. The overall incidence of cancer
      in men with this syndrome is similar to that of the general population, but some
      malignancies show a significantly higher prevalence in these patients. It is
      possible that the increased risk of developing certain cancers can be attributed
      to a direct effect of the chromosomal abnormality (the supernumerary X
      chromosome), or the combined action of the abnormal chromosomes and hormonal
      imbalances. Although data in the literature on cancer and KS are abundant, most
      of them are individual case reports. Only three epidemiological studies with
      relatively large cohorts provide data with greater reliability, although each has
      inherent imitations related to study design. This review paper summarizes the
      current knowledge about cancer risk from childhood to adulthood in patients with
      KS.

PMID- 24079076
TI  - Anorexia nervosa, obesity and bone metabolism.
AB  - Anorexia nervosa and obesity are conditions at the extreme ends of the
      nutritional spectrum, associated with marked reductions versus increases
      respectively in body fat content. Both conditions are also associated with an
      increased risk for fractures. In anorexia nervosa, body composition and hormones
      secreted or regulated by body fat content are important determinants of low bone
      density, impaired bone structure and reduced bone strength. In addition, anorexia
      nervosa is characterized by increases in marrow adiposity and decreases in cold
      activated brown adipose tissue, both of which are related to low bone density. In
      obese individuals, greater visceral adiposity is associated with greater marrow
      fat, lower bone density and impaired bone structure. In this review, we discuss
      bone metabolism in anorexia nervosa and obesity in relation to adipose tissue
      distribution and hormones secreted or regulated by body fat content.

PMID- 24079079
TI  - Who will meet the need?

PMID- 24079080
TI  - Geriatrics: a specialty that needs more.

PMID- 24079081
TI  - Where's your mountain and how will you climb it?

PMID- 24079082
TI  - Balancing act: Clinical considerations in end-stage dementia.

PMID- 24079083
TI  - Polymyalgia rheumatica: don't mistake it for other common presentations of aging.

PMID- 24079084
TI  - Alcohol abuse: take action against the no. 1 drug problem in this country.

PMID- 24079085
TI  - Asthma management: focus on four primary goals.

PMID- 24079086
TI  - "Action must be taken to create a safer NHS".

PMID- 24079087
TI  - NHS pressures to fuel agency spend.

PMID- 24079089
TI  - "Robbing Peter to pay Paul won't fix the problems caused by cuts".

PMID- 24079090
TI  - "Today's nurses must find time for the fluffy stuff".

PMID- 24079088
TI  - "Unjust comparisons with the private sector sap nurses' morale".

PMID- 24079091
TI  - Managing anorexia nervosa in the community.
AB  - This article describes the development and evaluation of a new specialist
      intensive community-based service for adults (those aged 18 years and above) with
      severe and enduring eating disorders (SEEDs). The service was developed by the
      Yorkshire Centre for Eating Disorders based in Leeds. We developed and evaluated
      a nurse-delivered community-based service that aimed to manage the complex needs
      of people with SEEDs without hospital admission. The service was shown to improve
      quality of life, reduce the number of hospital admissions and improve
      communication with other health professionals involved in service users' care.

PMID- 24079092
TI  - Providing high-quality end-of-life care universally.
AB  - The National End of Life Care Programme was launched in November 2004, and has
      been instrumental in delivering the Department of Health's (2008) End-of-Life
      Care Strategy and the National Institute of Health and Clinical Excellence's
      (2011) Quality Standard for End of Life Care for Adults. End-of-life care now
      sits within NHS Improving Quality. In this article we discuss an overview of the
      programme's successes, challenges and priorities for the future.

PMID- 24079093
TI  - A vision of the future for patient experience.
AB  - Although Liverpool Heart and Chest Hospital Trust has been rated top in the
      country for "overall care", we were aware that improvements could be made. We
      included staff in designing a patient experience vision to help them prioritise
      the needs of patients and their families in everything they do. Both staff and
      patients reported that the vision improved patient experience and it became an
      integral part of trust culture. This article describes the development and
      implementation of the vision.

PMID- 24079094
TI  - Campaign best practice in intravenous therapy.
AB  - Intravenous therapy is an integral part of nursing care but is associated with a
      high risk of infection. This article outlines a campaign that aimed to increase
      awareness of best practice for IV therapy and reduce the risks of healthcare
      associated IV infections in hospital and community settings.

PMID- 24079096
TI  - 60 seconds with June Girvin.

PMID- 24079095
TI  - Evaluating the impact of scholarships.
AB  - The Florence Nightingale Foundation offers scholarships in travel, research and
      leadership for nurses, midwives and allied health professionals. An evaluation
      revealed scholars considered the programmes of great value, allowing them the
      opportunity to develop personally and professionally.

PMID- 24079097
TI  - Putting patients first.

PMID- 24079098
TI  - Neutrophil function and periodontitis in alcohol-dependent males without medical
      disorders.
AB  - BACKGROUND: Periodontitis and immune dysfunction are often reported in alcohol
      dependent patients. Our objectives were to investigate the effects of alcohol
      exposure on neutrophil function and the associated consequential effects on the
      periodontium in a group of African American (AA) males with documented history of
      alcohol use without medical complications. METHODS: Thirty-three AA males with
      documented history of alcohol use were included in this analysis. All subjects
      were free from systemic illness. Blood levels of gamma-glutamyl transpeptidase
      (GGTP) were determined and used as a measure of alcohol consumption. Periodontal
      evaluations including attachment levels (AL) were recorded on 6 sites per tooth.
      Enumerative and functional neutrophil measures were obtained. RESULTS: GGTP blood
      levels inversely associated with neutrophil bacterial killing (NBK) (p = 0.04).
      Regression analysis, adjusting for risk factors associated with periodontitis,
      showed an inverse association between NBK and percent of sites with AL > or = 5
      mm (p <0.05) and a direct significant interaction between GGTP (> 51
      international units) and increasing NBK activity on percent of sites with AL > or
      = 5 mm (p < 0.05). CONCLUSIONS: In AA males with excessive alcohol use,
      neutrophils show depressed NBK. Depressed NBK was not associated with loss of
      periodontal attachment in this population. Furthermore, AA males with excessive
      alcohol use and uncompromised neutrophil function are at greater risk of
      periodontal tissue damage.

PMID- 24079099
TI  - Is the Schneiderian membrane thickness affected by periodontal disease? A cone
      beam computed tomography-based extended case series.
AB  - OBJECTIVE: The aim was to assess the thickness of Schneiderian membranes (SM) in
      patients with advanced periodontal disease. METHODS: 17 dentate patients (DG)
      scheduled for periodontal surgery on maxillary molars were consecutively
      recruited and cone beam computed tomographies performed for preoperative
      diagnosis. Twenty-one patients (EG) requiring cone beam computed tomography-based
      planning of implant placement in the edentulous posterior maxilla served as
      controls. RESULTS: Schneiderian membrane thickness measured from cone beam
      computed tomography was significantly greater in the dentate group compared to
      the edentulous group, both in the first (p = 0.028) and second (p < 0.001) molar
      position. In the dentate group, clinical signs of periodontal destruction
      (increased probing pocket depth or furcation involvement) were not associated
      with Schneiderian membrane thickness. Additional findings, such as periapical
      lesions (p = 0.008), and the distance between root tips and maxillary sinus
      revealed a significant association (p = 0.036) with Schneiderian membrane
      thickness. CONCLUSION: In molar regions with periodontal destruction,
      Schneiderian membrane thickening occurred, particularly in combination with small
      bone layers above the root tips or periapical lesions.

PMID- 24079100
TI  - One stage, full-mouth, ultrasonic debridement in the treatment of severe chronic
      periodontitis in smokers: a preliminary, blind and randomized clinical trial.
AB  - OBJECTIVE: The aim of this clinical trial was to assess the performance of a full
      mouth ultrasonic debridement protocol in the treatment of severe chronic
      periodontitis in comparison with scaling and root planing in a quadrant-wise
      procedure in smokers. MATERIALS AND METHODS: The trial consisted of 30
      participants presenting with periodontitis divided into 3 groups: Group FMUD -
      full-mouth ultrasonic debridement, i.e., one session of 45 minutes of ultrasonic
      instrumentation for smokers (n = 10), Group SRP- scaling and root planing
      performed in a quadrant-wise manner for smokers (n = 10), and Group Control - SRP
      for nonsmokers (n = 10), treated following the same protocol as the SRP group.
      The parameters evaluated were: plaque/bleeding on probing indices, probing pocket
      depth, relative recession, and relative probing attachment level at baseline, 45,
      90 and 180 days after therapy. RESULTS: Full-mouth ultrasonic debridement and
      scaling and root planing resulted in comparable gain of attachment 6 months after
      therapy. Both groups exhibited probing pocket depth reduction at all experimental
      periods as compared to baseline. Smokers, however, had less probing pocket depth
      reduction and relative probing attachment level gain compared to non-smokers,
      despite the mechanical protocol used (p < 0.05). Moreover, at 180 days,
      nonsmokers presented with fewer sites requiring re-treatment (probing pocket
      depth > 5 mm and bleeding on probing) than smokers (p < 0.05). CONCLUSIONS: Full
      mouth ultrasonic debridement and scaling and root planing result in comparable
      clinical outcomes for the treatment of smokers with severe chronic periodontitis.
      Despite the non-surgical technique used, smokers had a less favorable clinical
      response than non-smokers.

PMID- 24079101
TI  - Alveolar ridge preservation using resorbable bioactive ceramic composite: a
      histological study.
AB  - PURPOSE: The purpose of this study was to histologically evaluate newly generated
      vital bone using porous granules of bioactive and resorbable silica-calcium
      phosphate nanocomposite (SCPC) in extraction sockets. MATERIAL AND METHODS: Six
      patients with a non-restorable maxillary central incisor requiring extraction
      followed by implant placement participated in the study. Extraction sockets were
      grafted with granules of SCPC. After 6 months, a bone core sample was retrieved
      from the center of the healed socket for histologic analysis, and dental implants
      were placed. Alveolar bone width was clinically assessed immediately after tooth
      extraction and 6 months after bone grafting, at the time of implant placement.
      Alveolar bone height was radiographically assessed immediately after tooth
      extraction and 6 months after extraction. RESULTS: Histomorphometric analyses of
      sockets grafted with SCPC for 6 months revealed 46.8% +/- 14% new vital bone and
      2.5% +/- 1.5% graft material remnants. In these sockets, the mean bone height
      resorption over the 6-month period of healing was 1.6 mm +/- 1.5 mm. The mean
      bone width resorption of 2 mm +/- 0.7 mm was found at the bone crest. CONCLUSION:
      The results of this study suggest that SCPC graft material reduces the amount of
      change in alveolar ridge dimensions after tooth extraction and facilitates the
      regeneration of new vital bone.

PMID- 24079102
TI  - Risk management: Jolie's decision sparks debate, need for more education.

PMID- 24079103
TI  - Better prepared workforce, better retention: programs illustrate the value of
      mentoring.

PMID- 24079104
TI  - ANA urges California justices to protect schoolchildren, nursing practice.

PMID- 24079105
TI  - If you were in charge, what would RN practice look like?

PMID- 24079106
TI  - Verbally abused new nurses less likely to stay.

PMID- 24079107
TI  - Code interwoven in job performance, peer review.

PMID- 24079108
TI  - Scope of practice wins in Iowa, Nevada, Oregon and Rhode Island.

PMID- 24079109
TI  - Nurse residency program empowers new grads.

PMID- 24079110
TI  - RISNA member helps shape regulation education.

PMID- 24079111
TI  - Inspiring nurses, providing for patients: how certification makes a difference.

PMID- 24079112
TI  - The role of biomarkers in the detection and treatment of prostate cancer.

PMID- 24079113
TI  - Schistosomiasis.
AB  - Schistosomiasis is a parasitic infection caused by flatworms (trematodes). It is
      second only to malaria in public health significance, with over 200 million
      people infected worldwide, leading to severe consequences in 20 million persons
      and 100,000 deaths, annually. There are four species that cause intestinal
      schistosomiasis: Schistosoma mansoni; Schistosoma japonicum, Schistosoma mekongi,
      and Schistosoma intercalatum. Schistosoma haematobium causes urinary
      schistosomias, and is endemic in Africa and the Middle East, with the greatest
      prevalence in poor rural areas. Fibrotic changes in the urinary tract can lead to
      hydroureter, hydronephrosis, bacterial urinary infections, and ultimately, kidney
      disease or eventually bladder cancer. A rare lesion can also arise in patients
      infected with Schistosomiasis haematobium, resulting in squamous and
      adenosquamous prostate cancers. Imported diseases, such as schistosomiasis, are
      entering the United States through immigration via illegal aliens, refugees, and
      travelers. Schistosomiasis is a neglected tropical disease, and its global health
      impact is grossly underestimated.

PMID- 24079114
TI  - Characteristics of women with continued use of vaginal pessaries.
AB  - Vaginal pessaries have been shown to be a safe, effective treatment for pelvic
      organ prolapse, and in some cases, female urinary incontinence. There are limited
      data that predict long-term pessary use; therefore, the aim of this
      retrospective, exploratory study was to describe selected characteristics of
      women using a pessary for 12 months or longer in a nurse-run clinic.

PMID- 24079115
TI  - Case study: Transitional care for a patient with benign prostatic hyperplasia and
      recurrent urinary tract infections.
AB  - Chronic urologic conditions, including benign prostatic hyperplasia, recurrent
      urinary tract infections, and urinary incontinence, are common in older adults.
      This article highlights the urologic and transitional care needs of an elderly,
      cognitively impaired male during and after an acute hospitalization.
      Collaboration between the patient, his family, the advanced practice nurse,
      primary care providers, and outpatient urology office are described. The
      importance of mutual goal setting and a focused plan for transitional care are
      discussed.

PMID- 24079116
TI  - A hard mass discovered in the corpus spongiosum after difficult urethral
      catheterization: two case reports.
AB  - Male urethral catheterization is a common procedure rarely causing complications.
      Difficult urethral catheterization, however, can be problematic for both
      clinician and patient, leading to unexpected complications. This article will
      present two unreported cases of urethral trauma during difficult catheterization
      that resulted in the development of a hard, tumor-like mass in the corpus
      spongiosum. This is a rare complication that if not recognized might lead to
      unnecessary invasive interventions for the patient.

PMID- 24079117
TI  - A randomized trial of 2% lidocaine gel versus plain lubricating gel for
      minimizing pain in men undergoing flexible cystoscopy.
AB  - This article presents findings from a randomized trial of intra-urethral
      lidocaine versus a plain lubricating gel for pain reduction in men undergoing
      flexible cystoscopy. Compared with the plain gel, use of lidocaine resulted in
      significantly less pain during the procedure.

PMID- 24079118
TI  - Effect of weight on indwelling catheter use among long-term care facility
      residents.
AB  - This study examined the effect of obesity on the use of indwelling urinary
      catheters among long-term care facility residents and found initial increases in
      usage by weight category, which declined during the next 12 months.

PMID- 24079119
TI  - The Affordable Care Act: can we all achieve presidential health?

PMID- 24079120
TI  - Thoughts on transforming the service transition process.

PMID- 24079121
TI  - 2013 Behavioral Healthcare Champions.

PMID- 24079122
TI  - Merge for mission, not for money.

PMID- 24079123
TI  - A new beginning for New Beginnings Recovery Center.

PMID- 24079124
TI  - Health insurance enrollment: navigators to play key role in Obamacare.

PMID- 24079125
TI  - MHCD turns paper into treatment rooms--and income.

PMID- 24079126
TI  - Room to roam, room to recover.

PMID- 24079127
TI  - Update on traumatic brain injury.

PMID- 24079128
TI  - Getting beyond the 'gotcha' syndrome.

PMID- 24079129
TI  - Look beyond stigma to find passion--and support.

PMID- 24079131
TI  - Your future as a provider: it's all in the data.

PMID- 24079130
TI  - Escaping the 'poverty trap'.

PMID- 24079132
TI  - Positive outlook for dental implants.

PMID- 24079134
TI  - Focus on: Implant complications.

PMID- 24079133
TI  - Why don't general dentists place more implants?

PMID- 24079135
TI  - Confronting controversial issues in dental implant therapy, part I.

PMID- 24079136
TI  - Direct custom implant impression copings: a method for accurate impression of
      highly shaped peri-implant gingiva.

PMID- 24079137
TI  - Aesthetic zone challenges: restoring the dark tooth, part 2. Using elective
      orthodontic extrusion to modify gingival and bone levels.

PMID- 24079138
TI  - Conquering a difficult case, part 2. Lithium disilicate as a restorative solution
      for amelogenesis imperfecta.

PMID- 24079139
TI  - Management of a maxillary second molar.

PMID- 24079140
TI  - One-step in-office immediate dentures.

PMID- 24079141
TI  - Magnification alternatives: seeing is believing, part 2.

PMID- 24079142
TI  - Action for Dental Health: Dentists Making a Difference.

PMID- 24079143
TI  - What's the deal with 'EPL'? Coverage guards against employment claims.

PMID- 24079144
TI  - Changes to the NPI? What do I have to do now?

PMID- 24079145
TI  - Copier data security: a guide for businesses.

PMID- 24079146
TI  - Do you need a security camera in your office?

PMID- 24079147
TI  - The 1-2-3's of security cameras.

PMID- 24079148
TI  - How can volunteering help?

PMID- 24079149
TI  - Are internet travel sites any good?

PMID- 24079150
TI  - Derek Ichimura, DMD.

PMID- 24079151
TI  - Who is this ball player?

PMID- 24079152
TI  - Focusing for better accessibility of the Ethiopian Medical Journal.

PMID- 24079153
TI  - Peer-review and editorial process of the Ethiopian Medical Journal: ten years
      assessment of the status of submitted manuscripts.
AB  - BACKGROUND: The Ethiopian Medical Journal (EMJ) is a peer-reviewed journal, now
      50 years old. Many medical journals, including EMJ, follow a peer review system
      that has evolved from the 18th century process for reviewing submitted
      manuscripts. However, not much is known about peer review and editorial processes
      by many authors who submit manuscripts to the EMJ. OBJECTIVE: To describe
      procedures related to EMJ peer-review and editorial decision making and asses the
      status of manuscripts submitted to the journal in the ten year period between
      2001 and 2010. METHODS: All the minutes of the editorial board meetings of the
      ten years period 2001-2010 and relevant documents were reviewed. The minutes have
      details including date of submission, dates to and from reviewers, date of
      decision, number of assigned peer reviewers and comments given by reviewers for
      each submitted manuscript. The length of time took in the processes and the
      decision made (accepted or rejected) for each submitted manuscript was calculated
      from the dates. RESULTS: All submitted manuscripts passed through three stages:
      internal per-review by an editorial board member, external peer review by
      selected reviewers and final editing stage by an assigned editorial member. A
      total of 615 manuscripts were submitted to EMJ in the ten years period 2001-2010.
      Five hundred and one (82.7%) manuscripts were accepted for publication by peer
      reviewers, while 74 (12.2%) were rejected and 31 (5.1%) were withdrawn.
      Acceptance was lowest among original articles (81.3%) followed by teaching or
      review articles (84.3%) and case reports (89.3%). Thirty-two (8.4%) manuscripts
      were accepted within 6 months following submission and 50% were accepted within
      in one year of submission. About 6% of manuscripts were delayed for more than two
      years with a maximum delay of 43 months. CONCLUSION: Even though, there is a
      decline trend on the delay of processing manuscripts, EMJ has long to go in order
      to improve the quality of the journal and shorten the slow peer review process.
      Expansion of the use of electronic technology to communicate with authors and
      reviewers and motivating reviewers by conducting workshops and continuing medical
      educations are recommended to strengthen the process of peer review in the EMJ.

PMID- 24079154
TI  - Prevalence of diabetic retinopathy in Jimma University Hospital, Southwest
      Ethiopia.
AB  - BACKGROUND: Diabetic retinopathy accounts for 5% of global blindness and the
      incidence of diabetic blindness is increasing. Although the epidemiology of
      diabetic retinopathy has been well described in Western populations, there
      remains a paucity of prevalence data in many developing countries such as
      Ethiopia. OBJECTIVE: To determine the prevalence, pattern and associated risk
      factors of diabetic retinopathy. METHODS: A cross sectional hospital based study
      was done on a total of sampled 324 diabetic patients attending medical diabetic
      clinic at Jimma University Hospital from February to March 2009. Eye examination
      for diabetic retinopathy was carried out using slit lamp biomicroscope and 90D
      Volk lens, and clinical grading of diabetic retinopathy was done using the
      Diabetic Retinopathy Study and Early Treatment Diabetic Retinopathy Study
      guidelines. RESULTS: The prevalence of diabetic retinopathy was 41.4%. Of these,
      2.2% of the cases had severe non-Proliferative diabetic retinopathy while about
      6% of patients had clinically significant macular edema. Vision threatening
      diabetic retinopathy was found in 7.3% of patients. Only 14.5% of the patients
      had prior eye check. The mean duration of diabetes mellitus, mean fasting blood
      sugar, mean systolic blood pressure, and mean diastolic blood pressure were 6.26
      years, 158.8 mg/dl, 124.6 mmHg and 77.65 mmHg respectively. There was a
      statistically significant association between diabetic retinopathy and duration
      of diabetes, fasting blood sugar, and systemic blood pressure (p < 0.05).
      CONCLUSION: The prevalence of diabetic retinopathy was high, and only a small
      proportion of the study subjects had diabetic eye check up. There is a need for
      integration of the Medical Diabetic Clinic and Eye Clinic for preventive diabetic
      care, better referral system and coordinated diabetic screening program in the
      study setting.

PMID- 24079155
TI  - Dental anxiety: prevalence and associated factors, among children who visited
      Jimma University Specialized Hospital Dental Clinic.
AB  - INTRODUCTION: Dental fear in children has been recognized as an important
      condition in patient management for many years. Its effects have been shown to
      persist into adulthood which can lead to dental avoidance. OBJECTIVE: The aim of
      this study is to assess the magnitude and factors associated with dental fear
      among pediatric age group dental clinic attendees at Jimma University Specialized
      Hospital. METHODS: A cross-sectional study was conducted on 240 children who
      visited the dental clinic. Consecutive children who came to the dental clinic
      participated in the study. Dental anxiety was measured using Corah's Dental
      Anxiety Scale (CDAS) and Dental Fear Survey (DFS). Data was collected by directly
      interviewing the children and their parents. Chi-square statistics were used to
      explore for level of significance of associations between the variables. RESULTS:
      The mean age of the study population was 10.45 years (SD = 3.19). The rate of
      dental anxiety in the children was found to be 74.1% ranging from moderate to
      severe anxiety. More than a third of the participants (36.6%) had moderate level
      of anxiety; 17% of them had high level of anxiety and 20.5% of them had severe
      anxiety. Sex of the child was not significantly associated with dental anxiety
      whereas age of the child was found to be significantly associated (P = 0.029).
      Having previous experience of dental procedure in general was not associated with
      the level of anxiety, however, having painful previous experience was found to be
      associated with higher anxiety level. Also, there was significant association is
      found between anxiety levels of parents and children (P < 0.001). Moreover,
      children with dental anxiety were found to have avoidance of dental treatment.
      CONCLUSION AND RECOMMENDATION: The huge burden of dental anxiety and dental fear
      as well as its consequent dental avoidance found in this study calls for further
      study. Dentists should be aware of the pervasiveness of the problem and be ready
      to address the issue in routine clinical care.

PMID- 24079156
TI  - Visual impairment and road traffic accidents among drivers in Jimma Town,
      Southwest Ethiopia.
AB  - BACKGROUND: Vision play a vital role in driving where good and efficient visual
      functioning of the driver is essential. Any significant loss of visual function
      will diminish a driver's ability to operate a motor vehicle safely and will thus
      contribute to road traffic injury. However, there is little evidence indicating
      that defects of vision alone cause road traffic accidents. OBJECTIVE: To
      determine the impact of visual impairment and other factors on road traffic
      accident among vehicle drivers. METHODS: A cross-sectional descriptive study was
      conducted on 249 sampled drivers in Southwest Ethiopia. A pretested interviewer
      led questionnaire was used for interview and vision tests were done using
      Snellen's acuity chart and Ishihara pseudo-isochromatic plates. Statistical
      analyses were performed using SPSS version 16.0. RESULTS: The mean age of drivers
      was 33.6 years (SD +/- 10.3). The relative frequency of self reported road
      traffic accident was 15.3%. The prevalence of uncorrected binocular visual
      impairment was 1.6% and there was a significant association between visual
      impairment and road traffic accident (P < 0.05). Uncorrected refractive error was
      seen in 7.6% and 8.8% of drivers in the right and left eyes respectively, and
      3.2% of them had vision less than what is required to obtain driving license
      (visual acuity of 6/12). None of the drivers with refractive errors were wearing
      appropriate corrections. Color vision impairment was seen in 1.6% of the drivers.
      A significant proportion (9.6%) of the drivers did not have eye exam for their
      driving license. CONCLUSION: Uncorrected binocular visual impairment was strongly
      associated with road traffic accident. There is need for consistent inspection
      and screening, strict rules and regulations of licensing and health education for
      drivers to minimize road traffic accident.

PMID- 24079157
TI  - Clinical assessment of goiter and low urinary iodine concentration depict
      presence of severe iodine deficiency in pregnant Ethiopian women: a cross
      sectional study in rural Sidama, southern Ethiopia.
AB  - BACKGROUND: Maternal iodine nutrition during pregnancy is critical and deficiency
      during this period may compromise optimal fetal development. OBJECTIVE: To
      determine iodine status and knowledge of iodine deficiency disorders (IDD) of
      pregnant women in rural Sidama, southern Ethiopia. METHODS: A cross-sectional
      community-based study was conducted in three kebeles which were selected randomly
      from the eight kebeles in the study area using probability proportional to size
      methods. Data were collected in January, 2009, from 172 pregnant women. Main
      outcome measures were urinary iodine concentration (UIC), % of population with
      UIC < 20 microg/L, % of households using iodized salt, iodine content of salt and
      total goiter rate (TGR). RESULTS: Median UIC was only 15 microg/L compared to the
      150 microg/L minimum recommendation from WHO/UNICEF/ ICCIDD for pregnant women.
      The UIC of 60% of the women was < 20 microg/L. More than 90% of households were
      not using iodized salt and median salt iodine content was almost zero compared to
      the recommended 15-40 mg/kg. TGR was 49% (95% CI: 42, 56) which is much higher
      than the 5% TGR cut-off signifying a problem of public health significance. In
      addition, > 90% of participants didn't know about IDD, about the cause of goiter
      or why iodized salt is important. CONCLUSION: Results indicated the presence of
      severe iodine deficiency in the study population; urgent intervention, through
      universal salt iodization, and iodine supplementation to high risk groups is
      required.

PMID- 24079158
TI  - Patterns of mediastinal tumors operated at the Tikur Anbessa Hospital, Addis
      Ababa, Ethiopia over a six years period.
AB  - BACKGROUND: The mediastinum is the space that lies between the two pleural
      cavities containing many vital structures in it. When tumors or cysts arise in
      the mediastinum they can be either asymptomatic or present as space occupying
      lesions causing symptoms and signs by their effect on the neighboring organs.
      Though mediastinal tumors are routinely treated at the study center, there are no
      studies in Ethiopia concerning the patterns, and modes of treatments of
      Mediastinal space occupying lesions. OBJECTIVE: To review all the primary
      mediastinal tumors and cysts operated upon at the Tikur Anbessa Teaching
      Hospital, Addis Ababa University over a six year period, from August 2005-2011.
      METHODOLOGY: Clinical retrospective review. RESULTS: In the six years, 73
      patients were operated, 49 (67.1%) were males, the and male to female ratio being
      2.04:1. The mean age of patients was 35.9 +/- 10.5 years (range 14 to 74). Forty
      five (61.6%) had lesions of the anterior mediastinum, 23 (31.5%) in the posterior
      mediastinum and 5 (6.8%) in the middle. The commonest anterior mediastinal tumors
      were thymic origin (24/45), and thymic lesions were found more common in females
      (17:7 ratio). From the 23 patients with posterior mediastinal tumors, 18 had
      benign neurogenic tumors (4 of which were dumbbell tumors). Chest pain and
      shortness of breath (dyspnea) were the two most common symptoms in 31 (42.4%) of
      the patients. Twenty three patients (31.5%) were asymptomatic, and all had benign
      lesions. None of the malignant lesions were asymptomatic. Eleven (15%) patients;
      eight with anterior and three with posterior mediastinal masses, had undergone
      pre-operative tissue diagnosis procedure by image guided FNAC. Fifty-nine (80.8%)
      patients were operated with intent of therapeutic surgical procedures. There were
      28 (38.5%) midline sternotomies, 40 (54.7%) thoracotomies, four underwent a left
      sided mediastinotomies and one mediastinoscopy performed. The rate of malignancy
      in this study was 24 (32.8%), of which 19 (79.1%) were in the anterior
      compartment. A total of 13 (17.8%) patients had complications in the hospital and
      four (5.4%) of the patients died CONCLUSION: Primary mediastinal tumors are not
      so rare in the setting. We would also like to recommend further large scale
      prospective studies which also included long-term outcome so that we can further
      understand the situation in the country.

PMID- 24079159
TI  - Contrast-enhanced voiding urosonography--a feasible modality for the diagnosis of
      vesicoureteral reflux in a developing country.

PMID- 24079160
TI  - Gallbadder volvulus.
AB  - A 50 years old man was admitted to Wolayita Soddo Hospital, southern Ethiopia,
      with the complaints of sudden onset right upper quadrant pain with repeated
      vomiting. Physical examination was remarkable for a dehydration and abdominal
      tenderness. The patient showed no improvement on conservative treatment and hence
      underwent laparotomy. The intraoperative finding was a gallbladder volvulus and
      cholecystectomy was uneventful.

PMID- 24079161
TI  - Natural clovanes from the gorgonian coral Rumphella antipathies.
AB  - Three natural clovane-related sesquiterpenoids, 2beta-acetoxyclovan-9alpha-ol
      (1), 9alpha-acetoxyclovan-2beta-ol (2) and clovan-2beta,9beta-diol (3), were
      isolated from the gorgonian coral Rumphella antipathies. The structures of
      clovanes 1-3 were elucidated by spectroscopic methods and by comparison of the
      spectral data with those of known clovane analogues. This is the first time that
      clovanes 1-3 have been isolated from a natural source. Clovanes 1 and 2 displayed
      inhibitory effects on the generation of superoxide anions and the release of
      elastase by human neutrophils.

PMID- 24079162
TI  - Microbial biotransformation of 16alpha,17-epoxy-ent-kaurane-19-oic acid by
      Beauveria sulfurescens ATCC 7159-F.
AB  - Biotransformation of 16alpha,17-epoxy-ent-kaurane-19-oic acid (1) by Beauveria
      sulfurescens ATCC 7159-F led to the production of a new ent-kaurane diterpenoid,
      7beta,17-dihydroxy-ent-kaur-15-en-19-oic acid (7), and four other ent-kauranes (8
      - 11), all of which were identified as their methyl esters. Compounds 9 and 10
      were found to be new stereoisomers. Structures of these were established by the
      extensive usage of their spectroscopic characteristics.

PMID- 24079163
TI  - Establishment of in vitro adventitious root cultures and analysis of
      andrographolide in Andrographis paniculata.
AB  - Andrographolide is the principal bioactive component of the medicinal plant
      Andrographis paniculata, to which various diverse pharmacological properties are
      attributed. Traditionally, andrographolide was extracted from the leaves, stems
      and other parts of the plant. Leaves have the highest andrographolide content (2
      3%) in comparison with the other plant parts. Adventitious root culture of leaf
      explants of A. paniculata was studied using different strength MS medium
      supplemented by different concentrations of auxins and a combination of NAA +
      kinetin for growth and andrographolide production. Among the different auxin
      treatments in adventitious root culture, only NAA was able to induce adventitious
      roots. Adventitious roots grown in modified strength MS medium showed the highest
      root growth (26.7 +/- 1.52), as well as the highest amount of andrographolide
      (133.3 +/- 1.5 mg/g DW) as compared with roots grown in half- and full-strength
      MS medium. Growth kinetics showed maximum biomass production after five weeks of
      culture in different strength MS liquid medium. The produced andrographolide
      content was 3.5 - 5.5 folds higher than that of the natural plant, depending on
      the medium strength.

PMID- 24079164
TI  - New cycloartane-type triterpenes from Marcetia latifolia (Melastomataceae) and in
      silico studies on Candida parapsilosis protease.
AB  - We have previously reported the antimicrobial activity of the ethyl acetate
      extract of Marcetia latifolia, particularly against Candida parapsilosis. In this
      work we describe the isolation of two new cycloartane-type triterpenes, 28,29-bis
      norcycloartan-3beta,4alpha-diol (1) and 28,29-bis-norcycloart-24-en-3beta,4alpha
      diol (2) from the same extract. These compounds were mainly characterized by one-
      (1H, 13C and APT) and two-dimensional (1H-1H-COSY, 1H-1H-NOESY, HMQC and HMBC)
      NMR spectroscopy, mass spectrometry and comparison with published structural
      data. In addition, the activity of triterpenes 1 and 2 on the Candida protease
      target was investigated by in silico methods using molecular docking.

PMID- 24079165
TI  - Triterpene glycosides from the sea cucumber Eupentacta fraudatrix. Structure and
      biological action of cucumariosides I1, I3, I4, three new minor disulfated
      pentaosides.
AB  - Three new minor triterpene glycosides, cucumariosides I1 (1), I3 (2) and I4 (3)
      have been isolated from the Far Eastern sea cucumber Eupentacta fraudatrix.
      Structures of the glycosides were elucidated by 2D NMR spectroscopy and MS.
      Glycosides 1-3 belong to the group of cucumariosides I, havingbranched
      pentasaccharide carbohydrate moieties with two sulfate groups and possessing 3-O
      methyl-D-xylose as a terminal monosaccharide unit that is a characteristic
      feature of all the glycosides isolated from E. fraudatrix. Glycosides 1 and 2
      differ from each other by the side chain structures in the holostane aglycone
      moieties, while cucumarioside I4 (3) has a 23, 24, 25, 26, 27-pentanorlanostane
      aglycone with an 18 (16)-lactone. Cytotoxic activities of glycosides 1-3 against
      mouse spleen lymphocytes and ascite form of mouse Ehrlich carcinoma cells, along
      with hemolytic activity against mouse erythrocytes and antifungal activity were
      studied. Glycoside 1, having an aglycone side chain with a 24 (25)-double bond,
      possesses moderate activity in all the tests, while glycoside 2, having 23 (24)
      double bond and 25-hydroxy group in the side chain, and glycoside 3 with an
      aglycone with an 18 (16)-lactone and shortened side chain have either low
      activity or are non-active.

PMID- 24079166
TI  - Improved extraction and complete mass spectral characterization of steroidal
      alkaloids from Veratrum californicum.
AB  - Four steroidal alkaloids extracted from the roots and rhizomes of Veratrum
      californicum were separated by high performance liquid chromatography (HPLC) and
      identified using high resolution electrospray ionization time of flight tandem
      mass spectrometry (ESI-TOF-MS/MS) as veratrosine, cycloposine, veratramine, and
      cyclopamine. This paper compares ethanol and benzene as extraction solvents, HPLC
      solvent conditions leading to good separation of steroidal alkaloids, and MS/MS
      fragmentation patterns for the four steroidal alkaloids which have been released
      to the public database MassBank.jp. The reported Soxhlet extraction method nearly
      triples the recovery of steroidal alkaloids from V. californicum.

PMID- 24079167
TI  - TLC-image analysis of non-chromophoric tuberostemonine alkaloid derivatives in
      Stemona species.
AB  - A simple, selective, precise, and accurate thin-layer chromatographic (TLC) image
      analytical method was developed and validated for simultaneous quantification of
      the major components in the root extracts of Stemona tuberosa (tuberostemonine,
      tuberostemonine N and neotuberostemonine)), and S. phyllantha (tuberostemonine
      and tuberostemonine A). The analysis was performed by TLC on silica gel 60 F254
      aluminum plates using a mixture of dichloromethane: ethyl acetate: methanol:
      ammonium hydroxide (50:45:4:1) as mobile phase. Post-derivatization was employed
      by dipping the TLC plate into Dragendorff's reagent to visualize the spots. Image
      analysis of the scanned TLC plate was performed to detect the contents of
      tuberostemonine derivatives. The polynomial regression data for the calibration
      plots showed good linear relationships within the concentration range of 2-7
      microg/spot. The method gave satisfactory precision, accuracy, selectivity and
      could simultaneously quantify tuberostemonine, tuberostemonine A, tuberostemonine
      N and neotuberostemonine. Dried powdered roots of S. tuberosa grown in Thailand
      contained 1.31 +/- 0.28, 1.63 +/- 0.18 and 1.24 +/- 0.27% tuberostemonine,
      tuberostemonine N, and neotuberostemonine (dry weight), respectively, while S.
      phyllantha roots contained 1.39 +/- 0.14% tuberostemonine and 0.39 +/- 0.08%
      tuberostemonine A (dry weight). The proposed method was simple, inexpensive, and
      more accessible to apply for many local authorities and small laboratories.

PMID- 24079168
TI  - Two new compounds from gorgonian-associated fungus Aspergillus sp.
AB  - One new gamma-lactone derivative 5-hydroxy-3-isopropyl-4-methoxyfuranone (1) and
      one new lactam derivative dehydrated-marinamide (2), along with two known
      compounds marinamide (3) and marinamide methyl ester (4) were isolated from the
      fermentation broth of the marine gorgonian-associated fungus Aspergillus sp.
      SCSGAF0093. Their structures were elucidated on the basis of spectroscopic and
      spectrometric analysis. Compound 1 showed significant toxicity to brine shrimp
      (Artemia salina) with a median lethal concentration (LC50) of 1.25 microM, and 3
      inhibited protein tyrosine phosphatase 1B (PTP1B) with a half maximal inhibitory
      concentration (IC50) of 23.3 microg/mL.

PMID- 24079169
TI  - New metabolites from the algal associated marine-derived fungus Aspergillus
      carneus.
AB  - The new oxepin-containing (1) and quinazolinone (2) alkaloids and new
      dihydrobenzofuran derivative (3) have been isolated from a marine strain of
      Aspergillus carneus KMM 4638. The structures of these metabolites were determined
      by HR-MS and 1D and 2D NMR, along with Marfey's method.

PMID- 24079170
TI  - Chiroptical studies of flavanone.
AB  - Chiral HPLC coupled to electronic circular dichroism and laser optical rotation
      detection (HPLC-ECD-OR) permitted the on-line chiroptical characterization of
      both enantiomers of racemic flavanone (1) as ECD(-)310-OR(-)670-flavanone and
      ECD(+) 310-OR(+)670-flavanone for the first and second eluted peaks,
      respectively. Calculation of the ECD spectrum of one enantiomer at the TD
      DFT/DGTZVP level of theory yielded the (S)-ECD(-)310-OR(-)670 and (R)-ECD(+)310
      OR(+)670-1 absolute configuration, in agreement with the use of empirical rules
      for stereochemical assignment. Vibrational circular dichroism spectra of
      enantiopure compounds, obtained through fraction collection during repeated HPLC
      runs, were recorded and compared with theoretical traces produced from DFT
      calculations at the B3LYP/DGDZVP and B3PW91/DGDZVP levels of theory, which
      further confirmed the absolute configuration obtained from the on-line
      chiroptical data.

PMID- 24079171
TI  - Flavonoids with anti-HSV activity from the root bark of Artocarpus lakoocha.
AB  - From the MeOH extract of the root bark of Artocarpus lakoocha, a new compound
      5,7,2',4'-tetrahydroxy-6-geranyl-3-prenyl-flavone (1) was isolated, along with
      three known flavonoids (+)-afzelechin-3-O-alpha-L-rhamnopyranoside (2), (+)
      catechin (3) and cudraflavone C (4). Evaluation of these isolates for inhibitory
      effects against Herpes simplex virus (HSV) types 1 and 2 was carried out using
      the inactivation method. Compounds 1 and 4 showed moderate and weak activity
      against both types of HSV, respectively, whereas 2 and 3 were devoid of activity.

PMID- 24079172
TI  - Orphan flavonoids and dihydrochalcones from Primula exudates.
AB  - Two orphan flavonoids containing an oxepin structure in ring A and named as
      Primcortusin (1) and 3'-OH-Primcortusin (2) were isolated from leaf exudates of
      Primula cortusoides, while P. glutinosa exudates yielded two dihydrochalcone
      derivatives (3,4). These novel structures have not been detected in other species
      of Primula so far. Chemical structures were elucidated by 2D NMR and mas
      spectrometry. The nature of compounds 1 and 2 is discussed, and ideas about their
      possible origin and that of unsubstituted flavone and other irregular substituted
      Primula flavones are presented.

PMID- 24079173
TI  - First identification of alpha-glucosidase inhibitors from okra (Abelmoschus
      esculentus) seeds.
AB  - Infusion of roasted okra seeds has long been consumed in Turkey for diabetes
      mellitus therapy. Previous reports of a hypoglycemic effect observed in rats
      administrated with okra seed extract indicated a possible connection with
      inhibition of intestinal alpha-glucosidase. An attempt to identify active
      components was first herein conducted using alpha-glucosidase-inhibition-guided
      isolation, yielding two major flavonol glucosides named isoquercetin (2) and
      quercetin-3-O-beta-glucopyranosyl-(1"' --> 6")-glucoside (3). They selectively
      inhibited rat intestinal maltase and sucrase, in which isoquercetin (2) was 6-10
      times more potent than its related diglucoside 3. This result suggested that an
      increase in hydrophilicity by the additional glucose residue in 3 led to a
      significant decline in the inhibitory effect and raised the possible involvement
      of the free 3-OH in exerting the inhibition. Our postulation was evaluated by
      examining alpha-glucosidase inhibition of quercetin (1), and the aglycone of 2
      and 3, whose 3-OH is free from any glucose moiety. Interestingly, 1 displayed a
      broad inhibitory effect toward rat intestinal and baker's yeast alpha
      glucosidases, with improved potency. A kinetic study of 1 indicated that it
      inhibited maltase by two distinct mechanisms, in competitive (K(i) 462 microM)
      and noncompetitive (K(i) 2153 microM) manners, whereas the mechanism underlying
      the inhibition of sucrase was verified as being of a competitive behavior (K(i)
      218 microM).

PMID- 24079174
TI  - In vitro anti-proliferative effect of naturally occurring oxyprenylated
      chalcones.
AB  - As a continuation of our ongoing studies aimed to depict the effects and
      mechanism of action of naturally occurring oxyprenylated phenylpropanoids and
      polyketides, in this paper we describe the synthesis and in vitro anti
      proliferative effects of selected compounds belonging to the above cited classes
      of secondary metabolites on six cancer cell lines using the MTT colorimetric
      assay. Our study revealed that among the natural products tested, only
      oxyprenylated chalcones exhibited an appreciable effect (mean IC50 = 32 - 64
      microM), while substituted alcohols, phenylpropenes, naphthoquinones, and
      aminoacid derivatives were by far less active or inactive.

PMID- 24079175
TI  - Kaempferol 3,7,4'-glycosides from the flowers of Clematis cultivars.
AB  - A new kaempferol glycoside, kaempferol 3-O-alpha-rhamnopyranosyl-(1 --> 6)-beta
      glucopyranoside-7,4'-di-O-beta-glucopyranoside (1) was isolated from the flowers
      of Clematis cultivars "Jackmanii Superba" and "Fujimusume", together with the
      known compound kaempferol 3,7,4'-tri-O-beta-glucopyranoside (2). The chemical
      structures of the isolated kaemferol glycosides were established by UV, 1H and
      13C NMR spectroscopy, LC-MS, and characterization of acid hydrolysates.

PMID- 24079176
TI  - 7-O-methylpelargonidin glycosides from the pale red flowers of Catharanthus
      roseus.
AB  - Two new anthocyanidin glycosides were isolated from the pale red flowers of
      Catharanthus roseus 'Equator Apricot with Red Eye', and identified as 7-O
      methylpelargonidin 3-O-[6-O-(alpha-rhamnopyranosyl)-beta-galactopyranoside] and 7
      O-methylpelargonidin 3-O-(beta-galactopyranoside) by chemical and spectroscopic
      methods.

PMID- 24079177
TI  - Pyranocoumarin and triterpene from Millettia richardiana.
AB  - From the stem bark of a Madagascan endemic plant, Millettia richardiana Baill.,
      lonchocarpenin and betulinic acid were isolated and their structures established
      by spectroscopic methods. The analysis of dichloromethane fractions suggested the
      presence of beta-amyrin, lupeol, palmitic acid, linoleic acid and stearic acid.
      Except for beta-amyrin and lupeol, these compounds are described for the first
      time for the Millettia genus.

PMID- 24079178
TI  - A concise and efficient total synthesis of alpha-mangostin and beta-mangostin
      from Garcinia mangostana.
AB  - The concise, efficient synthesis of alpha-mangostin is described in eight simple
      steps with 8.3% overall yield. Highlights include a practical approach to
      construct the isopentene groups and other diverse groups at C-2 and C-8 of the
      xanthene skeleton through Claisen rearrangement and Wittig reaction. Meanwhile
      the first total synthesis of beta-mangostin is presented with a similar approach.

PMID- 24079179
TI  - Variation in the contents of neochlorogenic acid, chlorogenic acid and three
      quercetin glycosides in leaves and fruits of Rowan (Sorbus) species and varieties
      from collections in Lithuania.
AB  - Our research aim was to investigate the quantitative composition of
      neochlorogenic acid, chlorogenic acid, rutin, hyperoside and isoquercitrin in
      leaves and fruit of introduced rowan plants to Lithuania using a HPLC method. In
      leaf and fruit samples, quantitative estimation of neochlorogenic acid (in leaf
      samples 1.11-11.49 mg/g, in fruit samples 0.93-5.43 mg/g), chlorogenic acid (in
      leaf samples 2.74-21.91 mg/g, in fruit samples 0.55-7.50 mg/g), rutin (in leaf
      samples 0.03-4.88 mg/g, in fruit samples 0.02-0.39 mg/g), hyperoside (in leaf
      samples 0.15-7.44 mg/g, in fruit samples 0.02-1.19 mg/g) and isoquercitrin (in
      leaf samples 0.75-5.24 mg/g, in fruit samples 0.02-0.65 mg/g) was performed. In
      leaf samples, the total content of identified phenolic compounds ranged from 7.18
      to 35.74 mg/g. In fruit, raw material total content of neochlorogenic acid,
      chlorogenic acid and identified flavonoids varied from 2.24 to 11.19 mg/g.
      Comparison of raw material samples of Sorbus species according to their
      quantitative composition of identified phenolic compounds using cluster analysis
      singularized S. commixta leaf and fruit samples. These contained the highest
      contents of chlorogenic acid, hyperoside and isoquercitrin, but also the lowest
      contents of neochlorogenic acid and rutin. The highest contents of neochlorogenic
      acid were recorded for S. lancifolia leaves, and of rutin for S. anglica leaves.

PMID- 24079180
TI  - A new cytotoxic phenolic derivative from the roots of Antidesma acidum.
AB  - A new phenolic derivative, acidumonate (1), together with a synthetically known
      compound, 4-((E)-3,3-dimethylpenta-1,4-dienyl)-phenol (2), and sixteen known
      natural products, antidesmol (3), mellein (4), sitosterol (5), stigmasterol (6),
      5-cholesten-3beta-ol (7), 4-cholesten-3-one (8), 3-(1,1-dimethylallyl)-scopoletin
      (9), (-)- 5,7-dihydroxy-2-eicosyl-chromone (10), 2,5-dimethoxy-1,4-benzoquinone
      (11), barbatumol A (12), N-trans-feruloyltyramine (13), syringic aldehyde (14), p
      hydroxybenzoic acid (15), taxifolin (16), (+)-catechin (17) and gallocatechin
      (18), were isolated from the roots of Antidesma acidum. The structural assignment
      of the new compound was based on spectroscopic methods. All isolated compounds
      were evaluated for their cytotoxicity (KB and HeLa cells). Compound 1 showed good
      cytotoxicity against both cell lines (with IC50 values of 2.60 and 3.80
      microg/mL, respectively).

PMID- 24079181
TI  - A new nervogenic acid glycoside with pro-coagulant activity from Liparis nervosa.
AB  - In an effort to identify hemostatic components from Liparis nervosa (Thunb.)
      Lindl. using a bioactivity-guided fractionation approach, the n-BuOH extract was
      found to promote ADP-induced platelet aggregation and two compounds were isolated
      from the active extract. Compound 1 was a new nervogenic acid glycoside and the
      structure was elucidated as 3,5-bis(3-methyl-but-2-enyl)-4-O-[beta-D
      xylopyranosyl-(1 -->2)-beta-D-glucopyranosyl]-benzoic acid by extensive
      spectroscopic measurements. Adenosine (2) was isolated from this plant for the
      first time. Compound 1 also showed good pro-coagulant activity in vitro.

PMID- 24079182
TI  - Biologically active secondary metabolites from Asphodelus microcarpus.
AB  - Bioassay guided fractionation of the ethanolic extract of Asphodelus microcarpus
      Salzm.et Vivi (Asphodelaceae) resulted in the isolation of one new metabolite,
      1,6-dimethoxy-3-methyl-2-naphthoic acid (1) as well as nine known compounds:
      asphodelin (2), chrysophanol (3), 8-methoxychrysophanol (4), emodin (5), 2-acetyl
      1,8-dimethoxy-3-methylnaphthalene (6), 10-(chrysophanol-7'-yl)-10
      hydroxychrysophanol-9-anthrone (7), aloesaponol-III-8-methyl ether (8), ramosin
      (9) and aestivin (10). The compounds were identified by 1D and 2D NMR and
      HRESIMS. Compounds 3, 6 and 10 were isolated for the first time from this
      species. Compounds 3 and 4 showed moderate to weak antileishmanial activity with
      IC50 values of 14.3 and 35.1 microg/mL, respectively. Compound 4 exhibited
      moderate antifungal activity against Cryptococcus neoformans with an IC50 value
      of 15.0 microg/mL, while compounds 5, 7 and 10 showed good to potent activity
      against methicillin resistant Staphylococcus aureus (MRSA) with IC50 values of
      6.6, 9.4 microg/mL and 1.4 microg/mL respectively. Compounds 5, 8 and 9 displayed
      good activity against S. aureus with IC50 values of 3.2, 7.3 and 8.5 microg/mL,
      respectively. Compounds 7 and 9 exhibited a potent cytotoxic activity against
      leukemia LH60 and K562 cell lines. Compound 10 showed potent antimalarial
      activities against both chloroquine-sensitive and chloroquine-resistant strains
      of Plasmodium falciparum with IC50 values in the range of 0.8-0.7 microg/mL
      without showing any cytotoxicity to mammalian cells.

PMID- 24079183
TI  - Dibenzylbutane lignans from the stems of Schisandra bicolor.
AB  - Further investigation of the stems of Schisandra bicolor led to the isolation of
      a new dibenzylbutane lignan, named schibicolignan A (1), as well as five known
      compounds, namely bis[dibenzylbutane] (2), machilin A (3), macelignan (4),
      saururenin (5) and sphenanlignan (6). The structure of the new lignan was
      elucidated on the basis of extensive spectroscopic analysis. Antioxidant activity
      of 1-6 was also evaluated.

PMID- 24079184
TI  - Absolute configuration of falcarinol (9Z-heptadeca-1,9-diene-4,6-diyn-3-ol) from
      Pastinaca sativa.
AB  - Falcarinol (9Z-heptadeca-1,9-diene-4,6-diyn-3-ol; (1) is a polyacetylene commonly
      found in several plant families. The absolute configuration of naturally
      occurring 1 is not clear and contradictory results have been reported in the
      literature. Determination of the absolute configuration of 1 from Pastinaca
      sativa L. was carried out. Isolation of 95% pure 1 was performed via successive
      fractionation and preparative-HPLC. A racemic mixture comprised of 3R-1 and 3S-1
      was synthesized in order to confirm the absolute configuration of the isolated
      natural product using chiral HPLC. Based on a combination of chiral HPLC and
      specific rotation, 1 present in P. saliva was found to have a 3R absolute
      configuration (i.e. (3R, 9Z)-heptadeca-1,9-diene-4,6-diyn-3-ol).

PMID- 24079185
TI  - A new macrolide from a marine-derived fungus Aspergillus sp.
AB  - A new 16-membered macrolide named aspergillide D (1), along with six known
      compounds, including two polyketones (2-3) and four alkaloids (4-7), were
      isolated from the culture broth of a marine-derived fungus Aspergillus sp. SCSGAF
      0076. The structure of 1 was elucidated on the basis of NMR and mass spectra.
      Compound 5 showed an obvious inhibitory effect on influenza virus strains H1N1
      and H3N2.

PMID- 24079187
TI  - Determination of antiplasmodial activity and binding affinity of selected natural
      products towards PfTrxR and PfGR.
AB  - In our study, the binding affinities of selected natural products towards PfTrxR,
      PfGR, human TrxR and human GR were determined using a mass spectrometry based
      ligand binding assay. The in vitro antimalarial activity and cytotoxicity of
      these ligands were also determined. Catharanthine, 11-(OH)-coronaridine,
      hernagine, vobasine and hispolone displayed antiplasmodial activity against PfK1
      (IC50 = 0.996-3.63 microg/mL).

PMID- 24079186
TI  - HPLC-MS and GC-MS analyses combined with orthogonal partial least squares to
      identify cytotoxic constituents from turmeric (Curcuma longa L.).
AB  - We investigated the fingerprints of 48 batches of turmeric total extracts (TTE)
      by HPLC-MS-MS and GC-MS analyses and 43 characteristic peaks (22 constituents
      from HPLC-MS-MS; 21 from GC-MS) were analyzed qualitatively and quantitatively.
      An MTT {3-(4,5-dimethylthiazol-2-yl)- 2,5-diphenyltetrazolium bromide} assay was
      implemented to measure the cytotoxicity of the TTE against HeLa cells. Then we
      utilized orthogonal partial least squares analysis, which correlated the chemical
      composition of the TTE to its cytotoxic activity, to identify potential cytotoxic
      constituents from turmeric. The result showed that 19 constituents contributed
      significantly to the cytotoxicity. The obtained result was verified by canonical
      correlation analysis. Comparison with previous reports also indicated some
      interaction between the curcuminoids and sesquiterpenoids in turmeric.

PMID- 24079188
TI  - In vitro anti-inflammatory and antioxidant potential of Si-Miao-San, its
      modifications and pure compounds.
AB  - The ancient Chinese prescription Si-Miao-San (SMS), which is widely used for the
      treatment of various diseases, e.g. rheumatic disorders, has been modified
      (m1SMS, m2SMS). The purpose of this study was to investigate the anti
      inflammatory, antioxidant, and anti-tyrosinase effects of Si-Miao-San, of its two
      modifications, the component herbs, and its main pure ingredients. In vitro
      tyrosinase, 2,2-diphenyl-1-picrylhydrazyl (DPPH), and lipid peroxidation (LPO)
      assays were carried out in order to determine the inhibitory potential of the
      samples. The traditionally applied decoctions as well as their fractions (n
      hexane, DCM, n-BuOH) were tested for their activities in concentrations of 100
      microg/mL and 400 microg/mL, and the pure compounds in a range 6.25 microg/mL to
      100 microg/mL. In conclusion, the decoction of m2SMS exhibited strong antioxidant
      activity in the DPPH assay, while the decoction of the classical SMS formulation
      showed low activity. The present results have shown the modifications to be more
      efficient scavengers of free radicals, such as superoxide and peroxide radicals.
      In addition, the decoctions of the two modifications have been shown to be more
      potent tyrosinase inhibitors. These formulas may thus be used as antiinflammatory
      and anti-aging prescriptions, as they may help to prevent cell damage. This study
      clearly establishes the two modifications of Si-Miao-San as valuable sources of
      natural antioxidants and anti-inflammatory agents, and also as candidates in the
      search for modem pharmaceuticals.

PMID- 24079189
TI  - Smooth muscle relaxation activity of an aqueous extract of dried immature fruit
      of Poncirus trifoliata (PF-W) on an isolated strip of rat ileum.
AB  - We demonstrated that an aqueous extract of dried immature fruit of Poncirus
      trifoliate (PF-W) produces relaxation of intestinal smooth muscle using the ileac
      strips of a rat. Furthermore, the underlying mechanism of its relaxant activity
      was investigated. PF-W was prepared using the standard extraction protocol. A 1.5
      - 2 cm long rat ileac strip was placed in an organ bath with Tyrode's solution
      and smooth muscle contractility was recorded by connecting it to a force
      transducer. Various compounds were added to the organ baths, and changes in
      muscular contractility were measured. PF-W concentration-dependently induced
      relaxation of rat ileac strips that were contracted both spontaneously and via
      acetylcholine treatment. Various potassium channel blockers did not inhibit the
      relaxation by PF-W. No difference in the effect of PF-W was observed between
      ileac strips treated with low (20 mM) and high concentrations (60 mM) of KCl. PF
      W inhibited the contraction of rat ileac strips induced by extracellular calcium.
      PF-W acts as a potent smooth muscle relaxant, implicating its possible action as
      a rapid acting reliever for abdominal pains and a cure for intestinal convulsion.
      Considering that PF-W also exhibits prokinetic activity, its use in various
      gastrointestinal disorders seems promising.

PMID- 24079190
TI  - Invertebrate water extracts as biocompatible reducing agents for the green
      synthesis of gold and silver nanoparticles.
AB  - We report the use of water extracts of two invertebrates, snail body and
      earthworm, as biocompatible reducing agents for the green synthesis of gold and
      silver nanoparticles. The reaction conditions were optimized by varying the
      extract concentration, gold ion or silver ion concentration, reaction time, and
      reaction temperature. The gold and silver nanoparticles exhibited their
      characteristic surface plasmon resonance bands. Mostly spherical and amorphous
      shapes of the nanoparticles were synthesized. The average diameters of the gold
      and silver nanoparticles were 4.56 +/- 1.81 nm and 11.12 +/- 5.25 nm,
      respectively, when the extract of snail body was used as the reducing agent. The
      earthworm extracts produced gold and silver nanoparticles with average diameters
      of 6.70 +/- 2.69 nm and 12.19 +/- 4.28 nm, respectively. This report suggests
      that the invertebrate natural products have potential as biocompatible reducing
      agents for the green synthesis of metallic nanoparticles. This utility would open
      up novel applications of invertebrate natural products as nanocomposites and in
      nanomedicine.

PMID- 24079191
TI  - Elemental analysis of Ginkgo biloba leaf samples collected during one vegetation
      period.
AB  - The object of our work was the identification and quantification of inorganic
      elements in Ginkgo biloba L. leaves (Ginkgonis folium, Ginkgoaceae) by X-ray
      fluorescence analysis. The plant material was obtained from a 50-years-old female
      tree at the Comenius University Botanical Garden (Bratislava, Slovakia). Leaves
      were collected from early May to late September, with the last sample consisting
      of fallen leaves. The elements analyzed were: phosphorus, sulfur, potassium,
      calcium, scandium, iron, zinc, yttrium, molybdenum, tellurium, samarium,
      gadolinium, dysprosium, iridium, thallium and lead. The amounts of the monitored
      heavy metals were below the limits specified in Ph. Eur. 7 and PhS 1.

PMID- 24079192
TI  - Wild Thymbra capitata from Western Rif (Morocco): essential oil composition,
      chemical homogeneity and yield variability.
AB  - Essential oils (EO, 15 collective samples and 47 individual samples) of Thymbra
      capitata collected from Moroccan Western Rif were analyzed using gas
      chromatography (GC) in combination with retention indices (RI), gas
      chromatography-mass spectrometry (GC-SM) and 13C NMR spectroscopy. Twenty
      components were identified. Carvacrol (68.2%-85.9%) was by far the major
      component of all the samples, while the content of thymol (0.1-0.3%) was very
      low. Other components present in appreciable amounts were gamma-terpinene (up to
      8.9%), p-cymene (up to 7.1%), linalool (up to 4.4%) and (E)-beta-caryophyllene
      (up to 4.1%). In contrast, the yield of EO varied drastically from sample to
      sample (0.5-3.7%). No correlation could be established between yield of EO and
      altitude, pH, chemical composition and granularity of the soil. Cultivation under
      controlled conditions is suggested to improve the quantitative characteristics of
      carvacrol-rich Moroccan T. capitata.

PMID- 24079193
TI  - Essential oils of Chiliadenus lopadusanus (Asteraceae).
AB  - The essential oils from the leaves and flowers of Chiliadenus lopadusanus growing
      on Lampedusa Island were obtained by hydrodistillation and analyzed by GC-MS. The
      major component was camphor (39.4% in the leaves and 24.0% in the flowers),
      followed in the leaves by torreyol (6.7%), t-cadinol (5.2%) and 1,8-cineole
      (3.8%), while in the flowers by t-cadinol (15.2%), t-muurolol (5.1%) and torreyol
      (4.5%). Among the compounds identified, several seem to play a role in
      antibacterial, antifungal, allelopathic and spasmolytic activity. In addition,
      several compounds identified in this study seem to influence the attraction of
      Megachile (Eutricharaea) apicalis (Megachilidae) and Halictus (Seladonia) gemmeus
      (Halictidae), two hymenopteran here identified as pollinators of Chiliadenus
      lopadusanus.

PMID- 24079194
TI  - Chemical composition of the essential oil of Lepidagathis fasciculata from Bondla
      forest of Goa, India.
AB  - The hydro-distilled essential oil obtained from the flowering aerial parts of
      Lepidagathis fasciculata Nees was analyzed by gas chromatography equipped with a
      flame ionization detector (GC-FID) and gas chromatography coupled with mass
      spectrometry (GC/MS). A total of 38 compounds have been identified, representing
      91.2% of the total oil. The major constituents were delta-cadinene (14.4 %),
      gamma-curcumene (9.8%), sandaracopimarinal (6.6%), germacrene D-4-ol (6.1%),
      cembrene (5.0%), beta-calacorene (3.6%), ar-curcumene (3.3%), trans-4,10-epoxy
      amorphane (3.2%), abietatriene (2.9%), and alpha-cubebene (2.8%). The oil was
      rich in sesquiterpene hydrocarbons (43.8%).

PMID- 24079195
TI  - Leaf oil from Vepris madagascarica (Rutaceae), source of (E)-anethole.
AB  - The volatile components isolated from leaves of Vepris madagascarica (Baillon) H.
      Perier (Rutaceae), an endemic species of north-eastern, sub-humid forests of
      Madagascar, were investigated by GC (Retention Indices), GC-MS and 13C NMR
      spectroscopy. Oil samples obtained on laboratory and industrial scales exhibited
      similar composition, dominated by phenylpropanoids. (E)-anethole (78.2% and
      78.6%) was the major component followed by estragole (15.6% and 15.4%). In
      addition, trunk bark oil also contained (E)-anethole as its major component
      (84.6%), as well as various sesquiterpenes in low contents.

PMID- 24079196
TI  - Cardiovascular effects of the essential oil of Croton zehntneri leaves in DOCA
      salt hypertensive, conscious rats.
AB  - This study investigated the cardiovascular effects of the essential oil of Croton
      zehntneri (EOCZ) in deoxycorticosterone-acetate (DOCA)-salt hypertensive rats.
      Furthermore, in vitro experiments using isolated thoracic aortic rings were
      performed to assess the vascular effects of the EOCZ. In conscious hypertensive
      rats, intravenous (i.v.) injections of EOCZ (1-20 mg/kg) induced rapid (2-4 s)
      and dose-dependent hypotension and bradycardia (phase 1). The hypotension was
      followed by a significant pressor effect that was more evident at the higher
      doses (10 and 20 mg/kg) of EOCZ. Hypotension and bradycardia of EOCZ (phase 1)
      were abolished and respectively reversed into pressor and tachycardiac effects by
      methylatropine (1 mg/kg, i.v.) pretreatment. In isolated endothelium-intact
      aortic preparations, increasing concentrations (1-1000 microg/mL) of EOCZ relaxed
      the potassium-induced contraction in a concentration-dependent manner with an
      IC50 (geometric mean [95% confidence interval]) value of 202.0 [92.0-443.7]
      microg/mL. This vasorelaxant effect remained unaffected by either mechanical
      removal of functional vascular endothelium (IC50 = 189.0 [159.4-224.7] microg/mL)
      or the addition of atropine (1 microM) (IC50 = 158.6 [79.8-316.2] microg/mL) in
      the perfusion medium. These data show that i.v. administration of EOCZ in DOCA
      salt hypertensive rats induces a vago-vagal reflex decreases in heart rate and
      blood pressure (phase 1). EOCZ may induce a second and delayed hypotension due to
      its direct endothelium-independent vasorelaxant effects, but it seems to be
      buffered by the pressor component (subsequent to phase 1) of EOCZ. This pattern
      of blood pressure and heart rate responses to EOCZ seems unaltered by DOCA-salt
      hypertension, as was similar to that previously reported in conscious
      normotensive rats.

PMID- 24079197
TI  - Chemical composition and antioxidant activity of the essential oil and fatty
      acids of the flowers of Rhanterium adpressum.
AB  - The essential oil obtained by hydrodistillation of the flowers of Rhanterium
      adpressum Coss. & Durieu was analyzed using GC and GC-MS. The essential oil was
      very rich in monoterpene compounds. The major components identified were the
      monoterpene hydrocarbons: camphene (21.8%), myrcene (19.3%) and alpha-pinene
      (17.4%). Other compounds, including limonene, beta-pinene and terpinol-4-ol, were
      present in low content (4-6%). The composition of the fatty acids in the lipid
      extract obtained from the flowers was also investigated by GC and GC-MS. The main
      fatty acids identified were palmitic (47.4%), oleic (12.9%) and stearic acids
      (10.6%). The total phenolic contents and the antioxidant activities were also
      evaluated for both extracts. The total phenolic contents were determined using
      the Folin-Ciocalteu reagent and the antioxidant activities were measured using
      three different assays: DPPH (1,1-diphenyl-2-picrylhydrazyl) free radical
      scavenging activity, FRAP (ferric reducing antioxidant potential) and a
      molybdenum assay. As a result of these tests, the lipid extract exhibited the
      highest antioxidant activities in comparison with the essential oil extract.

PMID- 24079198
TI  - Chemical composition and biological activity of Conyza bonariensis essential oil
      collected in Merida, Venezuela.
AB  - The essential oil from aerial parts of Conyza bonariensis (L) Cronquist collected
      in Merida was obtained by hydrodistillation and analysed by GC/MS. The major
      components were trans-beta-farnesene (37.8%), trans-ocimene (20.7%) and beta
      sesquiphellandrene (9.8%). Cytotoxicity assay was also performed with the
      essential oil against HeLa (cervix carcinoma), A-459 (lung carcinoma) and MCF-7
      (breast adenocarcinoma) human cell lines and against normal Vero cells (African
      green monkey kidney) with IC50 values ranging from 1.4 to 45.8 microg/mL.
      Additionally, the essential oil presented a significant bactericidal effect
      against Bacillus cereus, while a moderate activity was observed against
      Staphylococcus epidermidis and Candida albicans.

PMID- 24079199
TI  - Chemical compositions, phytotoxicity, and biological activities of Acorus calamus
      essential oils from Nepal.
AB  - Four essential oils from the leaf (P23) and rhizomes (P19, P22, P24) of Acorus
      calamus L., collected from various parts of Nepal, were obtained by
      hydrodistillation and analyzed by GC-MS. From a total of 61 peaks, 57 compounds
      were identified among the four essential oils accounting for 94.3%, 96.2%, 97.6%,
      and 94.1% of the oils, respectively. All of the essential oils were dominated by
      (Z)-asarone (78.1%-86.9%). The essential oils also contained (E)-asarone (1.9%
      9.9%) and small amounts of gamma-asarone (2.0-2.3%), (Z)-methyl isoeugenol (1.5
      2.0%), and linalool (0.2-4.3%). Allelopathic testing of the rhizome oil showed
      inhibition of seed germination of Lactuca sativa and Lolium perenne with IC50
      values of 450 and 737 microg/mL, respectively. The rhizome essential oil
      demonstrated stronger seedling growth inhibition of L. perenne than of L. sativa,
      however. The rhizome oil also showed notable brine shrimp lethality (LC50 = 9.48
      microg/mL), cytotoxic activity (92.2% kill on MCF-7 cells at 100 microg/mL), and
      antifungal activity against Aspergillus niger (MIC = 19.5 microg/mL).

PMID- 24079200
TI  - Review on research of suppression male fertility and male contraceptive drug
      development by natural products.
AB  - Male contraceptive development in the present scenario is most viable aspect of
      research due to uncontrolled population growth in the world. In this respect
      investigators are busy to find out a safe male contraceptive drug. Researchers
      have started their finding for a suitable drug from natural sources because these
      are safe and easily acceptable for common man, most of natural sources are plants
      and their products. In this review 137 plants and their effects on reproduction
      and reproductive physiology are summarized. Some of them have intense effect on
      male reproductive system and do not produce any side effects. Reproductive
      toxicological studies are also important aspects of these kinds of researches, so
      it is important that drugs are safe and widely acceptable. An ideal male
      contraceptive can influence semen, testes, hormone level, accessory reproductive
      organs and general physiology of animals and produced some alterations. Many
      plants in this review are showing antifertility as well as antispermatogenic
      effects, so these may be used for further study for contraceptives development
      but it is important to find out the mechanism of reaction and further laboratory
      and clinical research on some plants are needed for final male contraceptive drug
      development. In conclusion this review will help for finding suitable plant
      products for male contraceptive clinical and laboratory studies.

PMID- 24079201
TI  - Sebaceous cysts with unpleasant twists: cutaneous myiasis with Dermatobia
      hominis.
AB  - Dermatobia hominis (human Bot fly) causes furuncular myiasis (larval infection)
      in Central and South America. This report describes a case in a member of the UK
      Armed Forces who had recently taken part in an overseas training exercise in
      Belize. The importance of clinical history (including travel history) is
      highlighted. We also describe the outcomes of conservative treatment and surgical
      intervention for separate lesions in the same patient.

PMID- 24079202
TI  - Anterior chamber gas bubbles in open globe injury.
AB  - We present a case of a 40-year-old soldier who was in close proximity to the
      detonation of an improvised explosive device (IED). Bubbles of gas were visible
      within the anterior chamber of his left eye. The authors propose that intraocular
      gas, present acutely after trauma, is diagnostic of open globe injury and is of
      particular importance in remote military environments.

PMID- 24079203
TI  - Penetrating brain injury: a case of survival following blast fragmentation
      injuries to the head.
AB  - We present a case of penetrating head injuries caused by blast fragmentation,
      along with other serious injuries (including to the arms, face and neck), where a
      good recovery was made despite an Injury Severity Score (ISS) of 75. We suggest
      that survival and outcome are reliant on several factors and cannot be predicted
      from ISS, velocity of penetrating injury or presenting Glasgow Coma Scale (GCS)
      alone.

PMID- 24079204
TI  - The 'tobruk method'--a useful tool in treating femoral shaft fractures in
      children.

PMID- 24079205
TI  - Mastering trauma surgery: MSc (trauma surgery).

PMID- 24079206
TI  - Biomedical science in the Royal Navy.

PMID- 24079207
TI  - The creation of the Battle Back Centre, Lilleshall; helping wounded, injured &
      sick service men & women to recover.

PMID- 24079208
TI  - A visit to Haslar Hospital, near Portsmouth, England. 1854.

PMID- 24079209
TI  - Tourniquets--reinventing the wheel.

PMID- 24079210
TI  - DMSTG--a truly tri-service medical Field Gun Crew 2013.

PMID- 24079211
TI  - The hepatitis C crisis in the African American Community: findings and
      recommendations.

PMID- 24079212
TI  - Lactose intolerance and health disparities among African Americans and Hispanic
      Americans: an updated consensus statement.
AB  - Dairy foods contribute nine essential nutrients to the diet including calcium,
      potassium and vitamin D; nutrients identified by the 2010 Dietary Guidelines for
      Americans as being "of public health concern" within the U.S. population. Milk
      and milk product intake is associated with better diet quality and has been
      associated with a reduced risk of chronic diseases or conditions including
      hypertension, cardiovascular disease, metabolic syndrome, Type 2 Diabetes and
      osteoporosis. Some research also indicates dairy food intake may be linked to
      reduced body fat, when accompanied by energy-restriction. On average, both
      African Americans and Hispanic Americans consume less than the recommended levels
      of dairy foods, and perceived or actual lactose intolerance can be a primary
      reason for limiting or avoiding dairy intake. True lactose intolerance prevalence
      is not known because healthcare providers do not routinely measure for it, and no
      standardized assessment method exists. Avoiding dairy may lead to shortfalls of
      essential nutrients and increased susceptibility to chronic disease. This updated
      Consensus Statement aims to provide the most current information about lactose
      intolerance and health, with specific relevance to the African American and
      Hispanic American communities. Topics covered include diagnostic considerations,
      actual and recommended dairy food intake and levels of consumption of key dairy
      nutrients among African Americans and Hispanic Americans; prevalence of self
      reported lactose intolerance among various racial/ethnic groups; the association
      between dairy food intake, lactose intolerance and chronic disease; and research
      based management recommendations for those with lactose intolerance.

PMID- 24079213
TI  - Disparities in the surgical treatment of colorectal liver metastases.
AB  - BACKGROUND: Hepatectomy is an accepted standard of care for patients with
      resectable colorectal liver metastases (CLM). Given that it is unclear whether
      disparities exist between different patient populations, a population-based
      analysis was performed to analyze this issue with regards to resection rates and
      surgical mortality in patients with CLM. METHODS: Using the Nationwide Inpatient
      Sample, characteristics and outcomes of adult patients with a diagnosis of
      colorectal cancer and colorectal metastases that subsequently underwent a liver
      resection during the years 1993-2007 were identified. Multivariate analysis was
      used to determine the effects of demographic and clinical covariables on
      resection rates and in-hospital mortality. RESULTS: Incident colorectal and liver
      metastases were identified in 138,565 patients; 3,528 patients (2.6%) underwent
      subsequent resection. African American and Hispanic race were associated with
      lower resection rates compared to Caucasian patients (adjusted OR 0.61 (0.52 -
      0.71) and 0.81 (0.68 - 0.96) respectively). Medicaid insurance was associated
      with decreased resection rates compared to private insurance (AOR 0.47 (0.40 -
      0.56)). The overall inpatient mortality rate was 3.1%. Multivariate analysis
      determined that mortality rate was correlated to both insurance status and
      geographic region. CONCLUSIONS: The national resection rate is significantly
      lower than has been reported by most case series. Race and insurance status
      appear to be correlated to the likelihood of surgical resection. In-hospital
      mortality is equivalent to the rates reported elsewhere, but is correlated to
      insurance status and region.

PMID- 24079214
TI  - Reaching beyond disparity: safely improving asthma control in the at-risk African
      American population.
AB  - In the United States, substantial racial disparities exist in asthma prevalence,
      etiology, morbidity and mortality, particularly between African Americans and
      white Americans. African-American patients with asthma have inadequate access to
      appropriate healthcare, insufficient asthma management guidance from their
      physicians and poor adherence to asthma medications-all factors that may
      contribute to disproportionate morbidity. Historically, African Americans have
      been under-represented in clinical asthma studies, and a paucity of data exists
      surrounding asthma treatment response. One controversial study from 2006 suggests
      an increased safety risk with the use of long-acting beta2-adrenergic agonists
      (LABAs) in African Americans. More recently, several studies have evaluated the
      use of LABAs in combination with an ICS in African-American populations. This
      article reviews the existing data on asthma treatment outcomes, with particular
      emphasis on the recently published short- and long-term studies of ICS/LABA
      products conducted in African-American populations with moderate-to-severe
      asthma. Overall, evidence suggests that if African-American patients with asthma
      are provided with access to well-trained physicians, appropriate asthma
      management and effective medications, existing disparities in asthma control
      between African-American and white populations may be overcome.

PMID- 24079215
TI  - Physician-patient race concordance from the physician perspective.
AB  - BACKGROUND: The benefits of racial/ethnic physician-patient concordance have been
      cited to support increasing the number of minority physicians. Few studies have
      examined the rates at which physicians of different race/ethnicity groups or
      specialties see concordant visits. We aim to determine whether differences exist
      in rates at which physicians of different race/ethnicity groups and physician
      specialties see visits by patients of concordant race/ethnicity. METHODS: We used
      data from the National Ambulatory Medical Care Survey, 2001-2006, a nationally
      representative survey of visits to private physician's offices. For physicians of
      each race/ethnicity group, the percentage of visits by patients in each
      race/ethnicity group was calculated. A concordant visit was defined as one in
      which a physician in a particular race/ethnicity group saw a patient of the some
      race/ethnicity group. Concordance rates were calculated overall, and for visits
      to primary care, medical specialties, and surgical specialties individually.
      RESULTS: White physicians see a higher percentage of concordant visits than any
      other race/ethnicity of physician (84.3%, p < 0.001 vs. all others), followed by
      Hispanic physicians and non-Hispanic black physicians, who had statistically
      similar rates (50.0%, and 46.8%, p > 0.05 for comparison), with non-Hispanic
      Asian physicians having the lowest rate of concordant visits (14.5%, p < 0.001
      vs. all others). Minority surgical and medical specialists have significantly
      lower rates of concordant visits (33.4% and 33.6% respectively) compared to
      minority primary care physicians (49.5%, p < 0.001 for both comparisons).
      CONCLUSION: Concordance rates from the physician perspective differ by physician
      race/ethnicity and by physician specialty.

PMID- 24079217
TI  - Controlled evaluation of a community pediatrics intervention to stimulate
      interest in careers in medicine among low-income eighth-grade students.
AB  - OBJECTIVE: To determine in a controlled cohort whether a one-day hospital
      visitation program will affect long-term student interest in a career in
      medicine. DESIGN: Historical cohort study using data from alumni survey in fall
      2008. SETTING: Two academic hospitals, in collaboration with a community-based
      educational organization. PARTICIPANTS: A total of 775 motivated, high-achieving
      eighth-grade students from low-income households throughout New Jersey. The
      students were enrolled from school year 2000-01 through 2007-08 in a fourteen
      month academic enrichment curriculum run by the New Jersey Scholars, Educators,
      Excellence, Dedication, Success program (NJ SEEDS) at four sites across the
      state. INTERVENTION: Students from two of the four sites participated in NJ SEEDS
      Hospital Day, a one-day experiential hospital visit. MAIN OUTCOME MEASURE: The
      percentage of alumni who stated the intention to pursue a medical degree.
      RESULTS: Thirty-nine of 175 (22%) survey respondents who were offered a Hospital
      Day program stated a plan to pursue a medical degree, compared with 42 of 288
      (15%) respondents not offered a Hospital Day experience (p = .03). Adjusting for
      gender, race, year of participation, and tutoring by a Hospital Day physician,
      the factors that significantly increased the likelihood of planning to pursue a
      medical degree were Hospital Day participation (adjusted odds ratio (OR) 2.0; 95%
      confidence intervals (CI) 1.2-3.4) and Asian race (adjusted OR 3.6; CI 1.3-10.1).
      CONCLUSIONS: An interactive hospital-based one-day pipeline program was
      associated with increased plans to pursue a medical degree among NJ SEEDS
      students when surveyed one to eight years following participation.

PMID- 24079216
TI  - Association of care in a medical home and health care utilization among children
      with sickle cell disease.
AB  - OBJECTIVE: Sickle cell disease (SCD) is marked by high utilization of medical
      services. The aim of this study was to determine whether having a patient
      centered medical home (PCMH) is associated with a reduction in emergency care
      (ED) utilization or hospitalizations among children with SCD. METHODS: We
      collected and analyzed data from parents of 150 children, ages 1 to 17 years, who
      received care within a large children's hospital. The primary dependent variables
      were rates of parent-reported ED visits and hospitalizations. The principal
      independent variable was parent-reported experience with an overall PCMH or its
      four individual components (regular provider, comprehensive care, family-centered
      care, and coordinated care). Multivariate negative binomial regression, yielding
      incident rate ratios (IRR), was used for analysis. RESULTS: Children who received
      comprehensive care had half the rate of ED visits (IRR 0.51, 95% confidence
      interval, 0.33-0.78) and nearly half the rate of hospitalizations (IRR 0.56, 95%
      confidence interval, 0.33-0.93) compared to children without comprehensive care.
      No other component of the PCMH was significantly associated with ED visits or
      hospitalizations. Children reported to have excellent/very good/good health
      status had lower odds of ED visits and hospitalizations compared to those
      reported to be in fair/poor condition. CONCLUSIONS: Children with SCD reported to
      experience comprehensive care had lower rates of ED encounters and
      hospitalizations after controlling for demographics and health status. The
      overall findings highlight that the provision of comprehensive care--having a
      usual source of care and no problems with referrals--may provide a strategy for
      improving pediatric SCD care.

PMID- 24079218
TI  - Gender- and ethnic-specific associations with obesity: individual and
      neighborhood-level factors.
AB  - OBJECTIVES: Gender- and ethnicity-specific groups face different risks for
      obesity, but little is understood about the factors that predict group-specific
      risks. We evaluated individual and neighborhood factors in relation to obesity.
      DESIGN: Cross-sectional surveys of adults (ages 18-100 years) from southeastern
      Pennsylvania were analyzed. Individual- and neighborhood-level factors were
      included in fully-adjusted regression models to estimate relationships with
      obesity for specific gender-ethnic groups. The study included 679 Asian women,
      655 Asian men, 4190 African-American women, 1568 African-American men, 1248
      Hispanic women, 586 Hispanic men, 11791 European American women, and 6547
      European American men. RESULTS: There were significant differences in the
      predictors of obesity by gender-ethnic groups. Obesity was differentially
      associated with age (p < 0.001, positively associated with middle age in African
      American men and in all women except Asian; positively associated with older age
      in European American women but inversely in African-American men and European
      American men), employment (p < 0.01, positively associated in African-American
      men and European American men) and poverty (p < 0.001, positively associated in
      Asian men, African-American women, and European American women). Reporting
      good/excellent health was differentially associated with less obesity (p < 0.01,
      no association for African-American men and Asians). Interestingly, neighborhood
      level effects, however, did not differ significantly by gender-ethnic group.
      Inverse neighborhood effects on obesity prevalence were observed in most groups
      for higher neighborhood education and family income. Direct associations with
      obesity were observed for neighborhood poverty and neighborhood smoking.
      CONCLUSIONS: We observed that individual- and neighborhood-level variables are
      associated with obesity. Several individual-level effects differ by gender-ethnic
      group.

PMID- 24079220
TI  - Marjolin's ulcer of a primarily grafted burn.

PMID- 24079219
TI  - Characterizing depression and comorbid medical conditions in African American
      women in a primary care setting.
AB  - BACKGROUND: African American women are more likely to seek treatment for
      depression in primary care settings; however, few women receive guideline
      concordant depression treatment in these settings. This investigation focused on
      the impact of depression on overall functioning in African American women in a
      primary care setting. METHODS: Data was collected from a sample of 507 African
      American women in the waiting room of an urban primary care setting. The majority
      of women were well-educated, insured, and employed. The CESD-R was used to screen
      for depression, and participants completed the 36-Item Short-Form Survey to
      determine functional status. RESULTS: Among the participants with depression,
      there was greater functional impairment for role-physical (z = -0.88, 95% CI = 
      1.13, -0.64) when compared to individuals with diabetes and hypertension.
      Individuals with depression also had greater role-emotional impairment (z = 
      1.12, 95% CI = -1.37, -0.87) than individuals with diabetes and hypertension.
      African American women with comorbid hypertension and depression had greater
      functional impairment in role-physical when compared to African American women
      with hypertension and no depression (t(124) = -4.22, p < 0.01). CONCLUSION:
      African American women with depression are more likely to present with greater
      functional impairment in role function when compared to African American women
      with diabetes or hypertension. Because African American women often present to
      primary care settings for treatment of mental illness, primary care providers
      need to have a clear understanding of the population, as well as the most
      effective and appropriate interventions.

PMID- 24079221
TI  - A lack of living donor renal transplantation for Asian children represents an
      opportunity to improve pediatric healthcare.
AB  - INTRODUCTION: The relationship between pediatric primary care practitioners and
      families provides an early opportunity to address ethnic/racial pediatric
      subspecialty health care disparities. Living donor pediatric renal
      transplantation is safe and more effective than deceased donor renal
      transplantation. The purpose of this study is to identify groups of children who
      may be less likely to receive living donor renal transplantation, as the first
      step in assisting pediatric clinicians to increase living donor renal
      transplantation. METHOD: We employed a retrospective cohort design. We analyzed
      data from the medical records of 80 children receiving renal transplantation over
      20 years in a large pediatric medical center. RESULTS: The proportions of
      children receiving a living donor renal allograft differed by ethnicity/race (P =
      .04). Specifically, children of Asian ethnicity/ race were significantly less
      likely than children of White ethnicity/race to receive a living donor renal
      allograft (P = .01). There were no significant differences in age at
      transplantation or wait time for deceased donor transplantation. DISCUSSION: We
      discuss the possible reasons for the discrepancy and potential directions for
      family-centered pediatric practice, policy, and research to address this
      potential pediatric healthcare disparity.

PMID- 24079222
TI  - [Advance in studies on NGR peptide modified liposome and its anti-tumor
      performance].
AB  - Aspargine-glycine-arginine (NGR)-containing peptides are targeted peptides which
      can be integrated with CD13 receptors on tumor vascular endothelial cells. NGR
      peptides are connected to liposomes to obtain NGR peptide-modified liposomes. By
      intravenous injection of these liposomes, NGR peptides can be combined with CD13
      receptors on tumor vascular endothelial cells, position liposomes in tumor
      tissues, and concentrate drug in liposomes in tumor, so as to enhance the
      antitumor effect. The article starts with NGR peptides, summarizes definition of
      NGR, NGR peptide-modified liposomes, strengths and weaknesses of NGR peptide
      modified liposomes in antitumor and the latest study orientation of NGR peptide
      modified liposomes, and looks into the future of studies on NGR peptide-modified
      liposomes.

PMID- 24079223
TI  - [Advance in studies on phospholipid compound of traditional Chinese medicines].
AB  - According to Chinese and foreign literatures and reports in recent years, this
      article introduced the latest advance in studies on phospholipid compound of
      traditional Chinese medicines in terms of its preparation mechanism, preparation
      process, characterization and transmembrane absorption. Under appropriate
      conditions, traditional Chinese medicines could generate phospholipid compound,
      whose physico-chemical property differs from the original drug, with a better
      absorption and improved bioavailability. Therefore, there is huge room for
      further study and development of phospholipid compound with traditional Chinese
      medicines.

PMID- 24079224
TI  - [Advances in studies on aryltetralin lactone lignans].
AB  - Natural aryltetralin lactone lignans existed in the plants of family
      Berberidaceae, Acanthaceae, Burseraceae, Verbenaceae, Euphorbiaceae, etc. Due to
      the antineoplastic and antiviral properties, it has become a hot research topic
      in medicinal chemistry. This review covers extraction and isolation,
      biosynthesis, plant origin, and structure and spectral characteristics of natural
      aryltetralin lactone lignans. It will provide a useful reference for the
      intensive studies and rational utilization of aryltetralin lactone lignans.

PMID- 24079225
TI  - [Data validation methods and discussion on Chinese materia medica resource
      survey].
AB  - From the beginning of the fourth national survey of the Chinese materia medica
      resources, there were 22 provinces have conducted pilots. The survey teams have
      reported immense data, it put forward the very high request to the database
      system construction. In order to ensure the quality, it is necessary to check and
      validate the data in database system. Data validation is important methods to
      ensure the validity, integrity and accuracy of census data. This paper
      comprehensively introduce the data validation system of the fourth national
      survey of the Chinese materia medica resources database system, and further
      improve the design idea and programs of data validation. The purpose of this
      study is to promote the survey work smoothly.

PMID- 24079226
TI  - [Cloning and bioinformatics analysis of SmNAC1 from Salvia miltiorrhiza hairy
      root].
AB  - In order to study function of NAC transcription in development, hormone
      regulation and the stress response of Salvia miltiorrhiza, the NAC transcription
      was cloned and analyzed. By retrieving cDNA database of S. miltiorrhiza hairy
      root one NAC unigene was found, then a full length of cDNA was cloned by
      designing specific primers and PCR amplifying. Using ORF finder it was found that
      the cDNA containing a NAC-AB conserved domain in N-terminal, so the cDNA was a
      NAC transcription factor, named as SmNAC1 (kF006346). Bioinformatics analysis
      showed that SmNAC1 had an open reading frame (ORF) of 591 bp encoding 196 amino
      acids. The calculated protein had isoelectric point (pI) of 4.36 with molecular
      weight about 21.66 kDa. The transcription level of SmNAC1 after dealing with
      yeast extract (YE) and silver ion (Ag+) in S. miltiorrhiza hairy root was
      markedly stimulated up regulating. It was 1.4 fold compared with the control
      after induction 2 h, and maintained 2.0 fold on 4-12 h after induction. SmNAC1
      may participate in regulation of stress response of YE + Ag+.

PMID- 24079227
TI  - [Anatomical structure and histochemical localization about rhizomes of five
      species of Polygonatum].
AB  - OBJECTIVE: The microscopic structure and histochemical localization of the
      Polygonatum sibiricum, P. cytonema, P. filipes, P. zanlanscianense and P.
      odoratum was studied. METHOD: Scanning electron microscope (SEM) and digital
      biological microscope (DBM) were applied in the research. RESULT: Venation bundle
      showed in three types included collateral, amphivasal and incomplete amphivasal
      bundles. Morphological differences of venation bundles could be seen under the
      fluorescence microscope. Calcium oxalate existed in the mucilage cells looked
      similar to columnar crystals under SEM. In rhizome of Polygonatum,
      polysaccharides presented in mucilage cells, saponins and volatile oil were found
      in ground tissue. CONCLUSION: Microstructure difference of rhizomes would be used
      for identification of the Polygonatum plants. Polysaccharides and saponins are
      distributed in different cells of Polygonatum plants.

PMID- 24079228
TI  - [Effect of NH4(+) -N/NO3(-)-N ratio in applied supplementary fertilizer on
      nitrogen metabolism and main chemical composition of Pinellia ternata].
AB  - OBJECTIVE: To study the effect of nitrogen forms on nitrogen metabolism and main
      chemical composition of Pinellia ternate. METHOD: Through the soilless
      cultivation experiment and based at the same nitrogen level and different NH4(+) 
      N/NO3(-) -N ratios, nitrate reductase (NR) activity, glutamine synthetase (GS)
      activity, the content of nitrate nitrogen and ammonium nitrogen in different
      parts of P. ternate were determined. The contents of total alkaloid, free total
      organic acids and guanosine in the tuber were determined. The yield of bulbil and
      tuber was calculated. RESULT: The test results showed that, with the NH4(+) 
      N/NO3(-) -N ratio increasing, the activity of nitrate reductase decreased, the
      content of nitrate nitrogen in the leaves, petioles and tuber increasing
      initially, then decreased, and the content of nitrate nitrogen in the root
      decreased. Meanwhile, with the NH4(+) -N/NO3(-) -N ratio increasing, the activity
      of glutamine synthetase in the leaves, petioles and root increased, the activity
      of glutamine synthetase in the tuber increasing initially, then decreased. The
      contents of ammonium nitrogen in the leaves, tuber and root increased initially,
      then decreased, and the contents of ammonium nitrogen in the petioles increased
      with the NH4(+)(-N/NO3(-)-N ratio increasing. The yield of bulbil and tuber were
      the highest at the NH4(+)-N/NO3(-) -N ratio of 75: 25. The content of total
      alkaloid and guanosine in the tuber were the highest at the NH4(+)-N/NO3(-) -N
      ratio of 0: 100, and the contents were 0.245% and 0.0197% respectively. With the
      NH4(+)-N/NO3(-) -N ratio of 50: 50, the content of free total organic acids was
      the highest, it reached 0.7%, however, the content of free total organic acids
      was the lowest at the NH4(+) -N/NO3(-) -N ratio of 0: 100. CONCLUSION: Nitrogen
      fertilization significant influences the nitrogen metabolism, the yield and main
      chemical composition of P. ternate.

PMID- 24079229
TI  - [HPLC determination of six lignans in different parts of Schisandra chinensis].
AB  - OBJECTIVE: To compare the content of six lignans of different parts of Schisandra
      chinensis. METHOD: Agilent TC-C18 (4.6 mm x 250 mm, 5 microm) was used with
      acetonitrile-water gradient system as mobile phase. Wave length was 250 nm. The
      flow rate was 1 mL x min(-1). Column temperature was 30 degrees C. RESULT: The
      total lignans content of wild Schisandra chinensis was higher than that of the
      cultivated varieties. The total lignans content of different parts varied
      significantly, wherein the root > main branch > side branches > leaf. CONCLUSION:
      This method is stable, reliable, can be used for the quality evaluation of
      different parts of Schisandra.

PMID- 24079230
TI  - [Effect of different plant growth regulators on yield and quality of Angelica
      dahurica var. formosana development].
AB  - OBJECTIVE: To investigate the effect of plant growth regulators on the growth and
      quality of Angelica dahurica var. formosana. METHOD: Five plant growth
      regulators: chlormequat chloride (CCC), Mepiquat chloride (PIX), Gibberellic acid
      (GA3), Paclobutrazol (PP333) and Maleic Hydrazide (MH) were sprayed in rosette
      stage, the effects of these plant growth regulators (PGRs) on the growth, yield
      and quality of A. dahurica var. formosanaw were observed. The biological traits
      were first measured and then imperatorin and isoimperatorin contents in roots
      were determined by HPLC. RESULT: Low concentration GA3 increased the yield while
      not influenced the premature bolting rate and the coumarin content. CONCLUSION:
      Spraying of GA3 (30 mg x L(-1)) could guarantee the growth and development of A.
      dahurica var. formosana to have a higher yield and maintain the active
      ingredients content in the root as well.

PMID- 24079231
TI  - [Molecular cloning of squalene synthase gene form Paris polyphylla and its
      expression in Escherichia coli].
AB  - OBJECTIVE: To clone the cDNA sequence of squalene synthase gene from Paris
      polyphylla, and characterize the biological features of the obtained SQS. METHOD:
      Using homology cloning and RACE technique, a full-length cDNA sequence of PpSQS
      gene was isolated from P. polyphylla. The obtained sequence was analyzed by
      bioinformatics softwares. A plasmid [named pET-30b (+)-PpSQS] was constructed for
      prokaryotic expression the recombinant PpSQS. RESULT: The full-length cDNA of
      PpSQS gene is 1 498 bp, which contains a 1 212 bp ORF. Sequence analysis
      indicated that PpSQS encoded 403 amino acids residues with a calculated molecular
      weight (MW) of 46.36 kDa and an isoelectric point (pI) of 6.83. SDS-PAGE results
      showed that the recombinant PpSQS was expressed in Escherichia coli BL21 (DE3) by
      inducing with 1 mmol x L(-1) IPTG. CONCLUSION: The full-length cDNA sequence of
      PpSQS gene was obtained from P. polyphylla, and its molecular features were
      consisted with classic SQS in plant. The recombinant PpSQS was successfully
      expressed in E. coli.

PMID- 24079232
TI  - [Detection of tobacco mosaic virus (TMV) in Rehmannia glutinosa f. hueichingensis
      by IC-RT-PCR].
AB  - OBJECTIVE: To establish a rapid, sensitive and efficient detection method for
      tobacco mosaic virus (TMV), and provide technical support of TMV detection of
      Rehmannia glutinosa f. hueichingensis. The virus-free plantlets could be produced
      on a large scale to ameliorate breed degeneration caused by viral disease.
      METHOD: Specific primers were designed based on the conserved region of coat
      protein(CP) gene of TMV. Immunocapture RT-PCR (IC-RT-PCR) was employed to detect
      TMV and the sequence of the products was detected. RESULT: The expected
      nucleotide acid fragments were amplified by IC-RT-PCR. The homology of nucleotide
      acid sequence and amino acid sequence were 95.29% and 96.7% between the PCR
      products and the CP gene of TMV (accession number AY555269). CONCLUSION: The
      method was established for the detection of TMV in R. glutinosa f. hueichingensis
      by IC-RT-PCR. This detection combined molecular biology technology with
      immunology, was convenient for a quick, sensitive and simple detection of TMV.

PMID- 24079233
TI  - [Preparation, in vitro evaluation of excipient-free dry powder inhalation of
      extraction of Trollius chinensis].
AB  - To prepare and evaluate dry powder inhalation (DPI) of extraction of Trollius
      chinensis Bunge (TCB). Orthodox design was employed to optimize the parameters of
      spray drying to prepare micronized TCB powder, the DPI was prepared by mixing
      micronized TCB powder and lactose. The results showed that the fine particle
      fraction (FPF) and emitted dose (ED) of micronized TCB powder was (21.07 +/-
      1.74)%, (75.31 +/- 21.05)%, respectively, and for DPI was (56.4 +/- 2.2)%, (95.9
      +/- 3.0)%, respectively. Therefore, the prepared DPI meeted requirements in the
      Chinese Pharmacopeia, indicating a good application prospect.

PMID- 24079234
TI  - [Preparation and in vitro permeation of tetramethylpyrazine hydrochloride
      transdermal gel].
AB  - The purpose of this study was to prepare tetramethylpyrazine hydrochloride
      transdermal gel and to study its permeation ability in vitro. The skin permeation
      ability was evaluated by Valian-Chien permeation cells with isolated rat skin.
      The concentration of tetramethylpyrazine in samples was determined by HPLC. The
      optimal formulation was composed with 5% azone, 5% peppermint oil, 8% sodium
      carboxymethylcellulose and 8% tetramethylpyrazine hydrochloride. The accumulative
      permeation amount of the gel was (6 731.87 +/- 102.31) microg x cm(-2) in 12
      h,and the permeation rate was (535.02 +/- 33.89) microg x cm(-2) x h(-1). The
      release profile in vitro was in line with zero-order formulation.
      Tetramethylpyrazine hydrochloride gel prepared in the study would be developed as
      a novel transdermal preparation.

PMID- 24079235
TI  - [Study on preparation process and stability of beta-cyclodextrin inclusion
      compound in volatile oil of Cinnamomum longepaniculatum leaves].
AB  - To study the optimum preparation process and stability of beta-cyclodextrin
      inclusion compound in volatile oil of Cinnamomum longepaniculatum leaves. The
      saturated aqueous solution method was adopted to prepare inclusion compounds for
      an orthogonal test. The inclusion compound productivity and the inclusion rate
      were taken as indexes for screening the inclusion processes. The inclusion effect
      was evaluated with the infrared spectrophotometry and TLC, and the stability
      under conditions of high temperature, high humidity and strong light was
      detected. Under optimum preparation conditions for inclusion, the ratio between
      volatile oil and beta-cyclodextrin was 1: 8 (mL: g), that between beta
      cyclodextrin and water was 1: 15, the inclusion temperature was 40 degrees C, and
      the inclusion time was 3 h. The results of spectrophotometry and TLC showed that
      the optimum conditions can generate beta-cyclodextrin inclusion compound in
      volatile oil of C. longepaniculatum leaves with certain light resistance, thermo
      stability and hygro-stability. Therefore the optimum inclusion process features
      simple operation and stable inclusion compounds.

PMID- 24079236
TI  - [Preparation and in vitro evaluation of curcumin CTPP-PEG-PCL micelles].
AB  - To synthetize 3-carboxypropyl-triphenylphosponium bromide-polycaprolacton-CTPP
      PEG-PC, and prepare curcumin CTPP-PEG-PCL micelles by using the self-assembled
      emulsion solvent evaporation method, in order to determine the critical micelle
      concentration (CMC) with the pyrene fluorescent probe technology, detect the
      particle size, entrapment efficiency (%), morpheme and in vitro release rate, and
      evaluate the cytotoxicity of hepatic stellate cells with MTT assay. The structure
      of CTPP-PEG-PCL had been identified by 1H-NMR spectra. Specifically, the CMC of
      polymer was 2.25 mg x L(-1), the average size was 190 nm, the drug content was
      (0.66 +/- 0.008) g x L(-1), and the entrapment efficiency was (94 +/- 0.6)%. The
      in vitro release results showed curcumin micelles had a significant higher
      inhibition ratio in the growth of hepatic stellate cells than crude curcumin (P <
      0.05). This suggested that CTPP-PEG-PCL micelles feature low CMC, high
      encapsulation efficiency and notable inhibition effect in growth of hepatic
      stellate cells.

PMID- 24079237
TI  - [Simultaneous determination of paeoniflorin, ferulic acid, prim-O
      glucosylcimifugin and 4'-O-beta-glucopyranosyl-5-O-methylvisamminol in zhengtian
      pills by HPLC].
AB  - To simultaneously determine paeoniflorin, ferulic acid, prim-O-glucosylcimifugin
      and 4'-O-beta-glucopyranosyl-5-O-methylvisamminol in Zhengtian pills. In the
      test, Insertil ODS-C18 column (4.6 mm x 250 mm, 5 microm) was adopted, with
      acetonitrile-0.05% phosphoric acid solution as the mobile phase for gradient
      elution. The flow rate was 1.0 mL x min(-1), the column temperature was 30
      degrees C and the detection wavelength was 230 nm. According to the results of
      the test, paeoniflorin, ferulic acid, prim-O-glucosylcimifugin and 4'-O-beta
      glucopyranosyl-5-O-methylvisamminol showed good linear relations between peak
      areas and sample sizes in 11.37-170.5, 2.188-32.82, 2.896-43.44, and 3.000-45.00
      mg x L(-1) (r = 0.999 9, 0.999 9, 1.000 0, 1.000 0), respectively. The average
      recoveries (n = 6) were 102.3% (RSD 1.2%), 99.71% (RSD 1.9%), 101.2% (RSD 1.2%),
      and 99.40% (RSD 2.4%), respectively. The above four components were determined in
      five batches of samples by using the established method, with satisfactory
      results. The method was so simple, accurate and highly reproducible that it could
      be used for quality control of the four components in Zhengtian pills.

PMID- 24079238
TI  - [A new lignan from stems of Sargentodoxa cuneata].
AB  - Sargentodoxae Caulis was prepared from the stems of Sargentodoxa cuneata. Twenty
      compounds from the the stems of S. cuneata collected in Huangshan Mountain, Anhui
      province, were isolated and purified by column chromatography on macroporous
      resin (HPD100), silica gel, Sephadex LH-20 and semi-preparative HPLC. Their
      structures were elucidated on the basis of physico-chemical properties and
      spectral data analyses as (7R,8S)-3,3 '-5-trimethoxy-4,9-dihydroxy-4',7-expoxy
      5',8-lignan-7'-en-9'-oic acid 4-O-beta-D-glucopyranoside(1), 1-O-(vanillic acid) 
      6-O-vanilloyl-beta-D-glucopyranoside(2), 4-hydroxyphenylethyl-6-O-coumaroyl-beta
      D-glucopyranoside(3), citrusin B(4), cinnamoside(5), (-) -isolariciresinol 4'-O
      beta-D-glucopyranoside (6), (-) -isolariciresinol 4-O-beta-D-glucopyranoside (7),
      1-O-(vanillic acid) -6-(3", 5"-dimethoxy-galloyl) -beta-D-glucopyranoside (8), 4
      hydroxyphenyl-ethyl-6-O-(E) -caffeoyl-beta-D-glucopyranoside (9), (-)
      syringaresinol 4'-O-beta-D-glucopyranoside (10), (-)-syringaresinol di-O-beta-D
      glucopyranoside (11), aegineoside (12), calceolarioside B (13), 4-hydroxy-3
      methoxy-acetophenone-4-O-alpha-L-rhamnopyranosyl-(1 --> 6)-beta-D-glucopyranoside
      (14), 4-hydroxy-3-methoxy-acetophenone-4-O-beta-D-apiofuranosyl-(1 --> 6) -beta-D
      glucopyranoside (15), (-) -epicatechin (16), salidroside (17), 3,4-dihydroxy
      phenyl ethyl-beta-D-glucopyranoside (18), chlorogenic acid (19) and
      protocatechuic acid (20). Compound 1 was a new compound and compounds 2-7 were
      isolated from this plant for the first time.

PMID- 24079239
TI  - [Chemical constituents from Usnea longgisima, a traditional mongolian medicine].
AB  - OBJECTIVE: To study the chemical constituents of the whole lichen of Usnea
      longissima. METHOD: The compounds were separated by silica gel, Sephadex LH-20
      chromatography and high performance liquid chromatography (HPLC). The structures
      of the compounds isolated were identified by physico-chemical properties and
      spectral analysis. RESULT: Ten compounds were isolated and their structures were
      identified as (4aR,9bS)-2,6-diactyl-3,4a,7,9-tetrahydroxy-8,9b-dimethyl-1-oxo
      1,4,4a, 9b-tetrahydrodibenzo [b,d]furan (1), (+)-usnic acid (2), orcinol (3), 18R
      hydroxydihydroalloprotolichensterinic acid (4), 5, 8-epidioxy-5alpha, 8alpha
      ergosta-6, 22E-dien-3beta-ol (5), ethyl everninate (6), arabitol(7), apigenin 7-O
      beta-D-glucuronide (8), 3-hydroxy-5-methoxy-2-methylbenzoic acid(9),
      friedelin(10). CONCLUSION: Compound 1 was a new compound. Compound 8 was isolated
      from genu Usnea for the first time and compounds 3, 4 and 7 were isolated from U.
      longissima for the first time.

PMID- 24079240
TI  - [Anti-complementary constituents of Pogostemon cablin].
AB  - Guided by anti-complementary activity, silica gel, Sephadex LH-20 and reversed
      phase column chromatographies were used for fractionation and isolation of the
      ethyl acetate and n-butanol soluble fractions of Pogostemon cablin. Eighteen
      compounds were obtained, including 15 flavonoids: 5-hydroxy-3,7,3',4'
      tetramethoxyflavone (1), 5-hydroxy-7,3',4'-trimethoxyflavanone (2), 5,4'
      dihydroxy-3,7,3'-trimethoxyflavone (3), 5-hydroxy-3,7,4'-trimethoxyflavone (4),
      5,4'-dihydroxy-7,3'-dimethoxyflavone (5), luteolin (6), quercetin-7,3', 4'
      trimethyl ether (7), ermanine (8), 3,5,7- trihydroxy-3', 4'-dimethoxyflavone (9),
      quercetin (10), apigenin (11), kaempferol (12), 5-hydroxy-7,3',4'
      trimethoxyflavone (13), kaempferol-7-O-beta-D-glucopyranoside (14) and kaempferol
      3-O-beta-D-glucopyranoside-7-O-alpha-L-rhamnoside (15); one triterpenoid: oleanic
      acid (16); and 2 phenolic acids: vanillic acid (17) and benzylalcohol (18). The
      isolation of 5, 7, 8, 12-15 and 18 from the Pogostemon genus is reported for the
      first time. All isolates were evaluated for their in vitro anti-complementary
      activities on the classical pathway and alternative pathway. And the targets of
      the most potent constituent in complement activation cascade were identified
      using complement-depleted sera. Compounds 3, 7, 10, 12 and 16 exhibited anti
      complementary activities toward the classical pathway and alternative pathway
      (CH50 0.072-1.08 g x L(-1), AP50 0.39-0.49 g x L(-1)), while 5 and 6 showed
      inhibitory effect on the classical pathway only. Mechanism study indicated that 7
      interacted with C1q, C2, C5 and C9 components.

PMID- 24079241
TI  - [Study on directional separation of picroside II from extract of traditional
      Chinese medicine by molecularly imprinted technology].
AB  - Picroside II, separated from Chinese herbal medicine, is an active compound with
      neroprotective activity. Molecularly imprinted polymers (MIPs) have high affinity
      toward template molecules synthesized by molecularly imprinted technology for its
      specific combined sites, which can overcome the shortcomings of traditional
      separation methods, such as complex operation and low efficiency. In this paper,
      MIPs were prepared by precipitation polymerization with picroside II as the
      template molecule, 1-vinylimidazole (1-Vinyl) as functional monomer, ethylene
      glycol dimethacrylate (EDMA) as cross-linker. The morphology of MIPs was
      characterized by scanning electronmicroscope (SEM) and its static adsorption
      capacity was measured by the scatchard equation. The results showed that
      picroside II MIPs have spherical shape, and most of them are uniform in size.
      Furthermore, the maximum binding capacity (Q(max)) of MIPs is 3.02 mg x g(-1),
      higher than that of non-imprinted polymers (NIPs). This result indicated that
      picroside II MIPs with good morphology and high targeted affinity toward the
      template molecules can be prepared by precipitation polymerization, which can be
      used to separate picroside II and its analogies from extract of Chinese herbal
      medicine. In addition, this method has the advantages of good environment and
      simple operation, which might offer a novel method for the efficient separation
      of picroside II in the traditional herbal medicines.

PMID- 24079242
TI  - [Study on optimization of drying method and its mechanism in Ginkgo biloba
      leaves].
AB  - To provide a scientific evidence for the initial primary processing method, an
      ultra-high performance liquid chromatography combined with a triple quadrupole
      electrospray tandem mass spectrometry (UPLC-MS/MS) was used to analyze the
      contents variation of catechins, flavonoids, flavonoid glycosides, biflavones,
      terpene lactones and phenolic acids during the process of drying in the sun, in
      the shade, and baked with 35, 45, 60, 80 degrees C, respectively. The results
      show that drying in the 80 degrees C is conducive to the accumulation of
      catechins, flavonoid glycosides, terpene lactones, better than the effects of
      other procedures. Therefore, the fast drying at 80 degrees C is beneficial for
      the retention of various types of active ingredient of Ginkgo biloba, and this
      method could be applied as a preferably dry processing.

PMID- 24079243
TI  - [Quality control of Lonicerae japonicae flos with standard reference extract].
AB  - The high price of the reference substances is an obstacle for the HPLC analysis
      of Lonicerae Japonicae Flos. To solve this problem, a new method based on the
      standard reference extract (SRE) was proposed. In this study, the extract of
      Lonicerae Japonicae Flos was calibrated, and the long-term stability was
      investigated. Different concentration solutions of SRE were prepared for
      establishment of the calibration profiles, and 6 organic acids were determined. T
      test was used for the comparison of the determination results via reference
      substances and SRE, and the results demonstrated that there is no significant
      difference between the two methods. The presented method can be used for the
      quality control of Lonicerae Japonicae Flos, and will also offer reference to
      resolve similar problems.

PMID- 24079244
TI  - [Study on quality standard of Psammosilene tunicoides based on absorbed active
      components in rat plasma].
AB  - A method for determintion of allantion in Psammosilene tunicoides was established
      by HPLC. Using alcohol as the extraction solvent, the subsequent filtrate of P.
      tunicoides was analysed by HPLC. Allantoin was successfully detected and
      separated by ZORBAX NH2 column (4.6 mm x 150 mm,5 microm) at wavelength of 220 nm
      and column temperature of 40 degrees C, with acetonitrile-water (93: 7) as mobile
      phase at a flow rate of 1.0 mL x min(-1). The results showed that it had a good
      linear relationship between the concent ration of allantion and chromatographic
      peak area. The linear correlation coefficient of allantion was 0.999 5 in 0.010 4
      0.166 g x L(-1). The relative standard deviation of six parallel injections was
      less than 2.1%. The average recoveries were ranged from 95.47% to 100.9%. This
      method was sensitive and accurate for the determination of allantion in P.
      tunicoides.

PMID- 24079245
TI  - [Study on quality evaluation of cimicifugae rhizoma from different producing
      areas by HPLC fingerprint].
AB  - To establish a fingerprint for Cimicifugae Rhizoma from different producing
      areas. Column kromasil (4.6 mm x 250 mm, 5 microm) was employed with acetonitrile
      0.1% formic acid solution as the mobile phase for gradient elution. The flow rate
      was 1.0 mL x min(-1), the detection wavelength was 254 nm. Twenty chromatographic
      peaks were extracted as the common peaks of fingerprint, and 21 batches of
      samples were compared and classified with such methods as similarity evaluation,
      cluster analysis and principle component analysis. The results showed 12 common
      peaks and three categories of samples. The method was so highly reproducible,
      simple and reliable that it could provide basis for quality control and
      evaluation of Cimicifugae Rhizoma from different producing areas.

PMID- 24079246
TI  - [Comparative study of chemical composition of pomegranate peel pomegranates
      inside and pomegranate seeds].
AB  - An HPLC fingerprint of pomegranate peel was established. Using chromatographic
      conditions, we compared the chemical composition of pomegranate peel, inside and
      seeds, and simultaneously determined the contents of gallic acid and ellagic
      acid. By comparison, we found that there were no significant differences between
      pomegranate peel and inside, but there was a big difference between pomegranate
      seeds and another two. The contents of gallic acid and ellagic acid of
      pomegranate peel respectively were 0.33%, 0.59%, while in pomegranate inside the
      result respectively were 0.52%, 0.38%. Content of ellagic acid from pomegranate
      seeds was only 0.01%. By study, we thought that when pomegranate peel was
      processed, pomegranate seeds should be removed, while pomegranate inside could be
      retained on the premise of full drying.

PMID- 24079247
TI  - [Experimental study on effect of anhydroicaritin phytosomes in preventing and
      treating bone loss and enhancing bone quality in ovariectomized osteoporosis
      rats].
AB  - OBJECTIVE: To explore the effect of anhydroicaritin phytosomes (AIP) in
      preventing and treating bone loss and enhancing bone quality in ovariectomized
      osteoporosis rats. METHOD: Seventy-two SD female rats were randomly divided into
      6 groups: the sham group, the model group, the estrogen group and AIP groups
      (low, middle, high). The sham group was only sham operated, and the remaining
      five groups were ovariectomized. One week after the ovariectomy, the rats were
      given 17 beta-estrogen and AIP (15, 30, 60 mg x kg(-1)) for consecutively three
      months, during which period their serum calcium (s-Ca), serum phosphorus(s-P),
      alkaline phosphate (ALP), urine calcium (u-Ca), urine phosphorus(u-P), urinary
      deoxypyridinoline (D-Pyr) and creatinine (Cr) were detected. Subsequently, rats
      were sacrificed, and their thighbone, second lumbar vertebrate and forth lumbar
      vertebrate were collected to detect bone mineral density (BMD), bone calcium (b
      Ca) and phosphorus (b-P), biomechanical properties and bone histomorphometric
      parameters. RESULT: Compared with the sham group, the model group showed a
      significant increase in serum ALP, u-Ca and D-Pyr /Cr, and reduction in BMD of
      femur, b-Ca and b-P, biomechanical properties (elastic load, maximum load, break
      load, stiffness), static parameters (total tissue area, trabecular area,
      trabecular perimeter) and dynamic parameters (% L Pm, BFR/BV and BFR/ TV), with
      metratrophia. Compared with the model group, ALP high and middle-dose groups and
      the estrogen group showed a decrease in serum ALP, u-Ca and D-Pyr/Cr, and growth
      in BMD of femur, b-Ca and b-P, biomechanical properties of the forth lumbar
      vertebrae (elastic load, maximum load, break load, stiffness), static parameters
      (total tissue area, trabecular area, trabecular perimeter) and dynamic parameters
      (% L Pm, BFR/BV and BFR/TV). The beta-estrogen group showed endometrial
      hyperplasia, whereas AIP groups showed no hyperplastic change. CONCLUSION: AIP
      could inhibit enhanced bone turnover induced by ovariectomy, improve BMD the
      biomechanical properties of vertebrae, without any stimulation on uterus.

PMID- 24079248
TI  - [Study on efficacy of compatibility between aconiti radix cocta and Pinelliae
      Rhizoma on basis of uniform design method].
AB  - OBJECTIVE: To study the effect of Aconiti Radix Cocta and Pinelliae Rhizoma with
      different matching proportions and doses on their analgic, anti-inflammatory,
      phlegm eliminating and cough relieving efficacies in mice. METHOD: The two
      factor, seven-level uniform design method was adopted to observe the effect of
      the oral administration with the combined decoction on the analgic, anti
      inflammatory, phlegm eliminating and cough relieving efficacies, with frequency
      of body torsions induced by acetum, ear swelling degree induced by
      dimethylbenzene, secretion of phenol red in tracheas and frequency of coughs
      induced by aqueous ammonia as indexes. Significant matching proportions and doses
      were collected for verification. RESULT: (1) The effect on the frequency of body
      torsions and ear swelling degree. The combined decoction could effectively reduce
      the frequency of body torsions and ear swelling degree. According to a regression
      analysis, Aconiti Radix Cocta and Pinelliae Rhizoma had the antagonism, which was
      maximized at the ratio of 10: 1, and minimized at the ratio of less than or equal
      to 1: 1. The frequency of body torsions and ear swelling degree increased first
      and then decreased along with the rise in the total dose; and a higher proportion
      of Aconiti Radix Cocta resulted in a faster speed in decrease or increase. (2)
      The effect on the secretion of phenol red in tracheas and frequency of coughs.
      The combined decoction could effectively increase the secretion of phenol red in
      tracheas and decrease the frequency of coughs. According to a regression
      analysis, Pinelliae Rhizoma and Aconiti Radix Cocta had the synergistic effect in
      the secretion of phenol red in tracheas, which was maximized with a total dose of
      more than 5 g x kg(-1) and a ratio of 1: 1. CONCLUSION: The compatible
      application of Pinelliae Rhizoma and Aconiti Radix Cocta can decrease the
      analgesic and anti-inflammatory effects of Aconiti Radix Cocta and promote the
      cough-relieving effect of Pinelliae Rhizoma, which vary according to different
      matching ratio and dose. This study provides experimental basis for indepth
      studies on the combined effect of Aconiti Radix Cocta and Pinelliae Rhizoma--two
      of eighteen incompatible pairs.

PMID- 24079249
TI  - [Study on analgesic and accompanying toxic and side effects of euodiae fructus
      based on clinical efficacy dose].
AB  - OBJECTIVE: To observe and study the toxic and side effects of water extracts from
      Euodiae Fructus accompanied with its efficacy analgesic dose and its mechanism,
      in order to provide experimental basis for the correlation between its "efficacy
      toxicity". METHOD: Mice were randomly divided into 5 groups according to weight,
      namely the normal group, the voltaren group, and Euodiae Fructus water extracts
      high, middle and low dose groups. Mice were administered with drugs for
      consecutively seven days, abdominally injected with acetic acid at 90 min and
      treated with hot plates after the last administration to establish the pain
      model, in order to the toxic and side effects accompanied with the efficacy.
      Besides toxic symptoms in mice, activities of ALT and AST, and content of BUN and
      Cr in serum were detected to calculate indexes in livers and kidneys. The other
      part of serum was collected to detect the content and activities of PGE2, MDA,
      SOD, NO, NOS, GSH and GSH-PX in serum. RESULT: Continuous oral administration of
      water extracts from Euodiae Fructus of efficacy dose could significantly decrease
      the frequency of writhe in mice and increase the hot plate pain threshold, with
      good dose-efficacy relationship. During the administration, mice showed such
      toxic symptoms as diarrhoea, idle move, dysphoria and slow growth of weight. The
      activities of both ALT and AST in serum and hepatic tissues were remarkably
      increased and the liver size remarkably increased, without notable chance in
      content of BUN and CR in serum. Kidney size increased in only the high dose
      group. The content and activities of PGE2, SOD, GSH, GSH-PX in serum notably
      decreased, where the content and activities of MDA, NO, NOS in serum increased.
      The above-mentioned changes gradually aggravated with the rise in dose. There was
      significant difference compared with the model group, showing 'dose-toxicity'
      relationship to certain extent. CONCLUSION: Continuous oral administration of
      certain dose of water extracts from Euodiae Fructus to mice can generate the
      toxic and side effects in liver accompanying with the analgesic effect, and show
      dose-dependence relationship to some extent. Its analgesic mechanism is related
      to the reduction of PGE, content in blood, while its toxic mechanism is related
      to oxidative injury to some extent.

PMID- 24079250
TI  - [Study on effect of weinaokang and bilobalide on autophagy and neurogenesis
      induced by focal cerebral ischemia reperfusion].
AB  - OBJECTIVE: To observe the protective effect of the Weinaokang (WNK) and its
      active compound bilobalide on focal cerebral ischemia reperfusion, and their
      mechanisms. METHOD: The 60-minute middle cerebral artery occlusion (MCAO) was
      adopted to establish the 24 h-14 d reperfusion model. The expression of Beclin-1
      was detected by the Western blotting technique. The transmission electron
      microscopy was used to observe ultrastructural changes. Neurogenesis was detected
      by the immunofluorescence staining. RESULT: WNK (20, 10 mg x kg(-1), ig) or its
      active compound bilobalide (10, 5 mg x kg(-1), ig) could promote the generation
      of mature neurons (BrdU(+) -MAP-2+) at the ischemic side, and inhibit expression
      of autophagy-related gene Beclin-1, so as to reduce the neuron injury induced by
      focal cerebral ischemia reperfusion. CONCLUSION: WNK and its active compound
      bilobalide can inhibit neuron autophagy and improve neurogenesis in ischemic
      peripheral area, suggesting that neurogenesis may be the intervention target for
      WNK to promote self-repairing of ischemic area.

PMID- 24079251
TI  - [Protective effect of soyasaponins on acute liver injury induced by D
      galactosamine and lipopolysaccharide in mice].
AB  - OBJECTIVE: To investigate the protective effect of soyasaponins on acute liver
      injury induced by D-galactosamine (GalN) and lipopolysaccharide (LPS) in mice.
      METHOD: The mice were randomly divided into five groups: the normal control, the
      model group, the silymarin (positive control) group, and soyasaponins high and
      low-dose groups. They were administered with drugs once every day for 7 days. At
      the end of the experiment, GalN and LPS were injected intraperitoneally to all of
      the groups except for the normal group to establish the acute liver injury model.
      The pathological changes were detected with hematoxylin & eosin (HE) staining,
      tumor necrosis factor-alpha (TNF-alpha) was detected by ELISA method, and the
      alanine aminotransferase (ALT), aspartate aminotransferase (AST), catalase (CAT),
      glutathione peroxidase (GPx), glutathione S-transferase (GST), reduced
      glutathione (GSH), malondialdehyde (MDA), nitric oxide (NO), and the activation
      of Caspase-3 and Caspase-8 were detected by the colorimetric method. RESULT:
      Soyasaponins could reduce the activities of serum ALT and AST, the acute hepatic
      injury induced by GalN/LPS, serum TNF-alpha level, hepatic NO and MDA contents,
      and the Caspase-3 and Caspase-8 activations of liver tissues, and increase the
      hepatic CAT, GPx, GST and GSH levels. CONCLUSION: Soyasaponins shows the
      protective effect on acute liver injury induced by GalN and LPS in mice, which
      may be related to its antioxidative ability and anti-liver apoptosis.

PMID- 24079252
TI  - [Study on functions and mechanism of curcumin in inducing colorectal carcinoma
      cells LoVo apoptosis].
AB  - OBJECTIVE: To discuss the biological function and regulation mechanism of
      curcumin in promoting human colorectal carcinoma (LoVo) cells apoptosis. METHOD:
      Conventional in vitro culture in human colorectal carcinoma cells LoVo, When 80%
      90% confluence was reached, cells were treated with curcumin at different
      concentrations (0-20 mg x L(-1)). Curcumin's effect on cell proliferation level
      was examined by MTT colorimetry. The ultrastructure of curcumin-treated LoVo
      cells were observed with transmission electron microscope (TEM). The amount of PI
      positive LoVo cells after the curcumin treatment were determined by flow
      cytometry. The cell apoptosis rate was detected by Annexin V-FITC/PI double
      staining. The mRNA level of Bax, Bcl-2, Caspase-3 and Bcl-xL were tested by means
      of RT-PCR. RESULT: MTT test indicates curcumin could inhibite the growth and
      proliferation of LoVo cells in a time- and concentration-dependent manner. TEM
      examination showed that curcumin can make LoVo cell morphological changes,
      showing the typical characteristics of apoptotic cells. Flow cytometry instrument
      analysis showed that curcumin can arrest cell cycle at S phase, and induce
      apoptosis of LoVo cells. RT-PCR test showed that curcumin can activate the
      expression of Bax and Caspase-3, inhibit the expression of Bcl-2 and Bcl-xL at
      the mRNA level. CONCLUSION: Curcumin can significantly inhibit the proliferation
      and induce the apoptosis of human colorectal carcinoma cells LoVo. Such
      biological effect may be associated with activating Caspase-3 signal channel by
      activating Bax expression and inhibiting Bcl-2 and Bcl-xL expression. This study
      lays an important foundation for further discussing the mechanism of curcumin in
      inducing human colorectal carcinoma LoVo apoptosis.

PMID- 24079253
TI  - [Preventive effect of ganlong capsule on chronic alcoholic hepatic injury in
      rats].
AB  - OBJECTIVE: To study the preventive effect of Ganlong capsule on chronic alcoholic
      hepatic injury in rats and its mechanism. METHOD: The rat chronic hepatic injury
      model was induced by intragastrically administered with gradient alcohol, once a
      day for 12 weeks. Efforts were made to detect the content of ALT, AST, TG, CHO,
      TNF-alpha in rat serum and GSH, SOD, MDA, ADH, Alb in hepatic tissues were
      detected, conduct a hepatic pathological examination, and pathological injury
      grading for livers. RESULT: Ganlong capsule could reduce the content of ALT, AST,
      TG in blood serum, MDA in hepatic tissues (P < 0.05), and enhance the activities
      of antioxidants such as SOD and GSH in hepatic tissues (P < 0.05). According to
      the liver histopathological observation, most structures of hepatic lobules in
      the model group were destroyed, with disordered liver cell cords, diffuse fat
      empty bubbles of different sizes in cytoplasm, focal necrosis and infiltration of
      inflammatory cells. All of treatment groups showed alleviation in rat liver
      injury to varying degrees. CONCLUSION: Ganlong capsule has a significant
      preventive effect to chronic alcoholic hepatic injury in rats.

PMID- 24079254
TI  - [Apoptosis effects of drug sensitivity leukemia cells induced by nano-realgar].
AB  - OBJECTIVE: To explore apoptosis-inducing effects of realgar nanoparticle (nano
      realgar) on drug-sensitive leukemia cells. METHOD: Preparation of nano-realgar
      was mechanical milled using a high-energy planetary ball mill. Using drug
      sensitive leukemia cells (K562) as target cells, MTT assay was used to detect the
      proliferating activity of K562 cells, and the cellular apoptosis was investigated
      with double staining of FITC-Annexin V and propidium iodide (PI) by flow
      cytometry. Flow cytometry (FCM) was employed to detect expression of
      intracellular Bax, Bcl-2, P-53 protein and the activity of Caspase-3. RESULT: The
      raw realgar was made to ultra-fine powder by ball milling, and the average
      diameter of the nanoparticle was (72.72 +/- 22.18) nm measured with electron
      microscopes. Nano-realgar significantly inhibited the proliferation of K562
      cells, Treated for 24, 48 and 72 hours, the 50% inhibitory concentration (IC50)
      was 43.48, 20.52, 16.07 mg x L(-1). After exposure to 20 mg x L(-1) and 50 mg x
      L(-1) nano-realgar for 48 hours, the apoptosis of K562 cells detected by Annexin
      V/PI staining was increased, the apoptotic rate of K562 cells was 10. 52% and
      73.25%. After the target cells were treated with 20 mg x L(-1) and 50 mg x L(-1)
      nano-realgar for 48 h, the expression of P-53, Bax, Bcl-2 markedly increased in a
      time and dose-dependent manner. After administration of 20 mg x L(-1) and 50 mg x
      L(-1) nano-realgar for 48 h, the percentage of BCRP+, P-gp+ and co-expressing P
      gp and BCRP cell population in K562 cells incrased dramatically. CONCLUSION: Nano
      Realgar significantly induced apoptosis of drug-sensitive leukemia cells.

PMID- 24079255
TI  - [Effect of neferine on hepatic stellate cells in collagen-I, TIMP-1 and MMP-2].
AB  - OBJECTIVE: To observe the effect of neferine on Collagen-I, TIMP-1 and MMP-2
      expressions and protein secretion of hepatic stellate cells. METHOD: The hepatic
      stellate cell line HSC-T6 was cultured in vitro, and then randomly divided into 5
      groups: the control group, the platelet-derived growth factor (PDGF) group and
      PDGF + neferine (2, 6, 10 micromol x L(-1)) groups. All of the groups were
      cultured for 48 h, and their cells were collected to extract mRNA and detect
      Collagen-I, TIMP-1 and MMP-2 expressions with RT-PCR. Their cell supernatants
      were also collected to determine the protein content of three factors with ELISA.
      RESULT: Compared with the control group, PDGF could remarkably increase the
      Collagen-I, TIMP-1 and MMP-2 expressions and protein secretion of hepatic
      stellate cells. Compared with the PDGF group, PDGF + neferine (6, 10 micromol x
      L(-1)) groups showed a notable decrease in the Collagen-I and mRNA expression and
      protein secretion along with the increase in the concentration, whereas the PDGF
      + neferine (2 micromol x L(-1)) group showed no significant change in the
      Collagen-I and mRNA expression and protein secretion. Compared with the PDGF
      group, three PDGF + neferine groups showed no notable change in MMP-2 expression
      and protein secretion. CONCLUSION: Neferine can inhibit the Collagen-I, TIMP-1
      and mRNA protein expression and protein secretion of PDGF-induced HSCs along with
      the increase in the concentration, but with not remarkable effect on the MMP-2
      expression and secretion.

PMID- 24079256
TI  - [Studies on biological characteristics and germination conditions of Thladiantha
      dubia seeds].
AB  - OBJECTIVE: To study the biological characteristics and find out the optimum
      condition for germination of seed of Thladiantha dubia Bunge for its standardized
      culturing. METHOD: The weight per 1 000 seeds, seed moisture content and seed
      viability were determined. The biological characteristics were studied and
      germination conditions of seed of T. dubia were tested under following
      conditions: different seed soaking time, different temperatures (15, 20, 25, 30,
      35 degrees C) and different irradiation time (0, 5, 10, 15, 20 min). RESULT: The
      average length, width and thickness of T. Dubia seed were 4.96, 3.25 and 1.08 mm,
      respectively. The weight per 1 000 seeds was 14.03 g; the seed moisture content
      was 10.10%; the seed viability was 90.33%. Under the same condition of light,
      temperature and other factors, the seed germination percentage and germination
      energy were the highest after seed soaking 24 h. The suitable temperature range
      of seeds was form 25 degrees C to 35 degrees C. Under different irradiation time,
      the seed germination percentage and germination energy were the highest after
      irradiation 10 min. In different germinating beds, the seeds germination
      percentage and germination energy were the highest on paper (TP), which was
      89.33%. CONCLUSION: The optimum condition for the germination of the seed of T.
      dubia is seed soaking 12 h, irradiation 10 min, 25-30 degrees C on filter paper.

PMID- 24079257
TI  - [Influence and countermeasure of technical barriers to trade on traditional
      Chinese medicine industry].
AB  - The authors proposed remedial measures for traditional Chinese medicine (TCM)
      products export faced with technical barriers to trade (TBT) according to
      analyzing the impact of TBT on TCM product export with economic theories, and
      putting forward countermeasures based on evaluation researches. TBT can be
      effectively coped with by the joint efforts of government, enterprises and
      industry association. Not only TBT can be broken through but also TCM product
      export can be expanded by the coordination and cooperation of our country and the
      society.

PMID- 24079258
TI  - [Effect of climate change on genuine medicinal materials producing areas during
      last 2 000 years--Alisma orientale and Citrus aurtantium as examples].
AB  - Climate in China has fluctuated greatly for last two thousand years. Also, the
      temperate-subtropical transition zone, as well as the distribution boundaries of
      subtropical biology and growth of suitable areas appear north-south lapse. In
      historical period, significant climate change will also be bound to the changes
      of the medicinal organism distribution suitable areas. The past dynasties herbal
      herbs have documented origin in detail, especially genuine medicinal materials
      producing areas. In this paper, Alisma orientale and Citrus aurtantium as
      examples, were used to elaborate the impact of climate change fluctuations on
      genuine producing area by evolution and change of genuine producing areas. The
      results showed that medicinal species were more sensitive to climate change such
      as A. orientale and C. aurtantium, its main producing areas or genuine producing
      area from north to south shifted in the Ming and Qing dynasties, consistent with
      the characteristics of climate change in China in last two thousand years.
      Factors prompted producing areas southward are not only low temperature and cold
      damage, and temperature and humidity have often synergistic effect. The human
      activities are more likely to exacerbate the impact.

PMID- 24079259
TI  - [Study on culture and philosophy of processing of traditional Chinese medicines].
AB  - According to cultural views and philosophical thoughts, this paper studies the
      cultural origin, thinking modes, core principles, general regulation and methods
      of processing, backtracks processing's culture and history which contains
      generation and deduction process, experienced and promoting process, and core
      value, summarizes processing's basic principles which are directed by holistic,
      objective, dynamic, balanced and appropriate thoughts; so as to propagate
      cultural characteristic and philosophical wisdom of traditional Chinese medicine
      processing, to promote inheritance and development of processing and to ensure
      the maximum therapeutic value of Chinese medical clinical.

PMID- 24079260
TI  - Distinct isolates of uropathogenic Escherichia coli differentially affect human
      sperm parameters in vitro.
AB  - Sperm motility and vitality are decreased in male genital tract infection.
      Uropathogenic Escherichia coli (UPEC) are frequently associated with sperm
      parameter loss, but there are no reports to date regarding the effects of
      different E. coli isolates on human spermatozoa. The aim of this work was to
      compare the effect in vitro of different E. coli isolates on human sperm
      parameters. Normal spermatozoa were incubated with E. coli isolated from nine men
      with urinary tract infection. After 1 h of incubation, sperm motility, vitality
      and mitochondrial membrane potential (DeltaPsim) were measured. The E. coli
      isolates were serotyped with specific antisera. Sperm motility was decreased with
      five of nine E. coli isolates. Two UPEC were typed as O6 strains, and they did
      not decrease sperm motility in the same experimental conditions as the other five
      isolates, despite the described high pathogenicity of the O6 strain in urogenital
      infections. Neither UPEC analysed affected vitality or DeltaPsim. UPEC isolates
      were shown to be heterogeneous in their effects, suggesting the need to
      characterise the pattern defining the pathogenicity of E. coli on human
      spermatozoa.

PMID- 24079261
TI  - Clinicopathological and extensive immunohistochemical study of a type II
      pleuropulmonary blastoma.
AB  - Pleuropulmonary blastoma (PPB) is a rare malignant dysontogenetic neoplasm
      primarily affecting younger children, even in newborns with an unfavorable
      outcome. PPB is histologically composed of a primitive, variably mixed
      blastematous and sarcomatous components, and exclusively subclassified as type I
      (purely cystic), type II (both cystic and solid elements) and type III
      (completely solid) by increasing histological evidence of malignancy. At present,
      well-documented cases or cases of truly precise presentation of either
      pathological or immunohistochemical findings in PPB are rare. The authors report
      one case of PPB in a 44-month-old child presenting as a solid and cystic mass
      with special emphasis on its radiological, histopathological and
      immunohistochemical aspects. The histological diagnosis was PPB, which would
      belong to the type II category. 

PMID- 24079263
TI  - School time--again.

PMID- 24079262
TI  - The reliability of the physical examination to guide fluid therapy in adults with
      severe falciparum malaria: an observational study.
AB  - BACKGROUND: Adults with severe malaria frequently require intravenous fluid
      therapy to restore their circulating volume. However, fluid must be delivered
      judiciously as both under- and over-hydration increase the risk of complications
      and, potentially, death. As most patients will be cared for in a resource-poor
      setting, management guidelines necessarily recommend that physical examination
      should guide fluid resuscitation. However, the reliability of this strategy is
      uncertain. METHODS: To determine the ability of physical examination to identify
      hypovolaemia, volume responsiveness, and pulmonary oedema, clinical signs and
      invasive measures of volume status were collected independently during an
      observational study of 28 adults with severe malaria. RESULTS: The physical
      examination defined volume status poorly. Jugular venous pressure (JVP) did not
      correlate with intravascular volume as determined by global end diastolic volume
      index (GEDVI; r(s) = 0.07, p = 0.19), neither did dry mucous membranes (p =
      0.85), or dry axillae (p = 0.09). GEDVI was actually higher in patients with
      decreased tissue turgor (p < 0.001). Poor capillary return correlated with GEDVI,
      but was present infrequently (7% of observations) and, therefore, insensitive.
      Mean arterial pressure (MAP) correlated with GEDVI (rs = 0.16, p = 0.002), but
      even before resuscitation patients with a low GEDVI had a preserved MAP. Anuria
      on admission was unrelated to GEDVI and although liberal fluid resuscitation led
      to a median hourly urine output of 100 ml in 19 patients who were not anuric on
      admission, four (21%) developed clinical pulmonary oedema subsequently. MAP was
      unrelated to volume responsiveness (p = 0.71), while a low JVP, dry mucous
      membranes, dry axillae, increased tissue turgor, prolonged capillary refill, and
      tachycardia all had a positive predictive value for volume responsiveness of
      <=50%. Extravascular lung water >=11 ml/kg indicating pulmonary oedema was
      present on 99 of the 353 times that it was assessed during the study, but was
      identified on less than half these occasions by tachypnoea, chest auscultation,
      or an elevated JVP. A clear chest on auscultation and a respiratory rate <30
      breaths/minute could exclude pulmonary oedema on 82% and 72% of occasions
      respectively. CONCLUSIONS: Findings on physical examination correlate poorly with
      true volume status in adults with severe malaria and must be used with caution to
      guide fluid therapy. TRIAL REGISTRATION: Clinicaltrials.gov identifier:
      NCT00692627.

PMID- 24079264
TI  - Evaluation of skin cancer in Northern California Kaiser Permanente's store-and
      forward teledermatology referral program.
AB  - OBJECTIVE: To determine whether teledermatology referrals yield a shorter time to
      biopsy of the most common types of skin cancer versus conventional dermatology
      referrals. SUBJECTS AND METHODS: A retrospective chart review was performed of
      California's Central Valley Kaiser Permanente conventional dermatology or
      teledermatology referrals that yielded a positive skin cancer biopsy over a 7
      month period. Four primary care clinics at Kaiser Permanente's Stockton Medical
      Center in California's Central Valley were included. Patients who were studied
      were treated for squamous cell carcinoma of skin, basal cell carcinoma of skin,
      and malignant melanoma. We compared the time interval between initial evaluation
      and biopsy of the most common types of skin cancer for teledermatology versus
      traditional referrals from primary care. RESULTS: Our study criteria were met by
      293 patient cases (58% conventional referrals and 42% teledermatology referrals).
      The mean time to biopsy of skin cancer was 13.8 days for conventional referrals
      (median, 12.0 days) versus a mean of 9.7 days (median, 9.0 days) for
      teledermatology referrals (p<0.0001). CONCLUSIONS: The use of teledermatology in
      remote areas results in a shorter time to biopsy than traditional referral
      methods as a result of improved triaging measures.

PMID- 24079265
TI  - Analysis of the internal configurations of droplets of liquid crystal using flow
      cytometry.
AB  - We report the use of flow cytometry to identify the internal ordering (director
      configurations) of micrometer-sized droplets of thermotropic liquid crystals
      (LCs) dispersed in aqueous solutions of adsorbates (surfactants and
      phospholipids). We reveal that changes in the configurations of the LC droplets
      induced by the adsorbates generate distinct changes in light scattering plots
      (side versus forward scattering). Specifically, when compared to bipolar
      droplets, radial droplets generate a narrower distribution of side scattering
      intensities (SSC, large angle light scattering) for a given intensity of forward
      scattering (FSC, small angle light scattering). This difference is shown to arise
      from the rotational symmetry of a radial LC droplet which is absent for the
      bipolar configuration of the LC droplet. In addition, the scatter plots for
      radial droplets possess a characteristic "S-shape", with two or more SSC
      intensities observed for each intensity of FSC. The origin of the experimentally
      observed S-shape is investigated via calculation of form factors and established
      to be due to size-dependent interference effects that differ for the forward and
      side scattered light. Finally, by analyzing emulsions composed of mixtures of
      bipolar and radial droplets at rates of up to 10,000 droplets per second, we
      demonstrate that flow cytometry permits precise determination of the percentage
      of radial droplets within the mixture with a coefficient of determination of 0.98
      (as validated by optical microscopy). Overall, the results presented in this
      paper demonstrate that flow cytometry provides a promising approach for high
      throughput quantification of the internal configurations of LC emulsion
      microdroplets. Because large numbers of droplets can be characterized, it enables
      statistically robust analyses of LC droplets. The methodology also appears
      promising for quantification of chemical and biological assays based on adsorbate
      induced ordering transitions within LC droplets. 

PMID- 24079266
TI  - Faraday rotation due to excitation of magnetoplasmons in graphene microribbons.
AB  - A single graphene sheet, when subjected to a perpendicular static magnetic field,
      provides a Faraday rotation that, per atomic layer, greatly surpasses that of any
      other known material. In continuous graphene, Faraday rotation originates from
      the cyclotron resonance of massless carriers, which allows dynamical tuning
      through either external electrostatic or magneto-static setting. Furthermore, the
      rotation direction can be controlled by changing the sign of the carriers in
      graphene, which can be done by means of an external electric field. However,
      despite these tuning possibilities, the requirement of large magnetic fields
      hinders the application of the Faraday effect in real devices, especially for
      frequencies higher than a few terahertz. In this work we demonstrate that large
      Faraday rotation can be achieved in arrays of graphene microribbons, through the
      excitation of the magnetoplasmons of individual ribbons, at larger frequencies
      than those dictated by the cyclotron resonance. In this way, for a given magnetic
      field and chemical potential, structuring graphene periodically can produce large
      Faraday rotation at larger frequencies than what would occur in a continuous
      graphene sheet. Alternatively, at a given frequency, graphene ribbons produce
      large Faraday rotation at much smaller magnetic fields than in continuous
      graphene. 

PMID- 24079268
TI  - The impact of task relevance and degree of distraction on stimulus processing.
AB  - BACKGROUND: The impact of task relevance on event-related potential amplitudes of
      early visual processing was previously demonstrated. Study designs, however,
      differ greatly, not allowing simultaneous investigation of how both degree of
      distraction and task relevance influence processing variations. In our study, we
      combined different features of previous tasks. We used a modified 1-back task in
      which task relevant and task irrelevant stimuli were alternately presented. The
      task irrelevant stimuli could be from the same or from a different category as
      the task relevant stimuli, thereby producing high and low distracting task
      irrelevant stimuli. In addition, the paradigm comprised a passive viewing
      condition. Thus, our paradigm enabled us to compare the processing of task
      relevant stimuli, task irrelevant stimuli with differing degrees of distraction,
      and passively viewed stimuli. EEG data from twenty participants was collected and
      mean P100 and N170 amplitudes were analyzed. Furthermore, a potential connection
      of stimulus processing and symptoms of attention deficit hyperactivity disorder
      (ADHD) was investigated. RESULTS: Our results show a modulation of peak N170
      amplitudes by task relevance. N170 amplitudes to task relevant stimuli were
      significantly higher than to high distracting task irrelevant or passively viewed
      stimuli. In addition, amplitudes to low distracting task irrelevant stimuli were
      significantly higher than to high distracting stimuli. N170 amplitudes to
      passively viewed stimuli were not significantly different from either kind of
      task irrelevant stimuli. Participants with more symptoms of hyperactivity and
      impulsivity showed decreased N170 amplitudes across all task conditions. On a
      behavioral level, lower N170 enhancement efficiency was significantly correlated
      with false alarm responses. CONCLUSIONS: Our results point to a processing
      enhancement of task relevant stimuli. Unlike P100 amplitudes, N170 amplitudes
      were strongly influenced by enhancement and enhancement efficiency seemed to have
      direct behavioral consequences. These findings have potential implications for
      models of clinical disorders affecting selective attention, especially ADHD.

PMID- 24079267
TI  - Bacterial Mg2+ homeostasis, transport, and virulence.
AB  - Organisms must maintain physiological levels of Mg(2+) because this divalent
      cation is critical for the stabilization of membranes and ribosomes, for the
      neutralization of nucleic acids, and as a cofactor in a variety of enzymatic
      reactions. In this review, we describe the mechanisms that bacteria utilize to
      sense the levels of Mg(2+) both outside and inside the cytoplasm. We examine how
      bacteria achieve Mg(2+) homeostasis by adjusting the expression and activity of
      Mg(2+) transporters and by changing the composition of their cell envelope. We
      discuss the connections that exist between Mg(2+) sensing, Mg(2+) transport, and
      bacterial virulence. Additionally, we explore the logic behind the fact that
      bacterial genomes encode multiple Mg(2+) transporters and distinct sensing
      systems for cytoplasmic and extracytoplasmic Mg(2+). These analyses may be
      applicable to the homeostatic control of other cations. 

PMID- 24079269
TI  - Decreasing trends in cardiovascular mortality in Turkey between 1988 and 2008.
AB  - BACKGROUND: Cardiovascular disease (CVD) mortality increased in developed
      countries until the 1970s then started to decline. Turkey is about to complete
      its demographic transition, which may also influence mortality trends. This study
      evaluated trends in coronary heart disease (CHD) and stroke mortality between
      1988 and 2008. METHODS: The number of deaths by cause (ICD-8), age and sex were
      obtained from the Turkish Statistical Institute (TurkStat) annually between 1988
      and 2008. Population statistics were based on census data (1990 and 2000) and
      Turkstat projections. European population standardised mortality rates for CHD
      and stroke were calculated for men and women over 35 years old. Joinpoint
      Regression was used to identify the points at which a statistically significant
      (p < 0.05) change of the trend occurred. RESULTS: The CHD mortality rate
      increased by 2.9% in men and 2.0% in women annually from 1988 to 1994, then
      started to decline. The annual rate of decline for men was 1.7% between 1994
      2008, whilst in women it was 2.8% between 1994-2000 and 6.7% between 2005-2008 (p
      < 0.05 for all periods).Stroke mortality declined between 1990-1994 (annual fall
      of 3.8% in both sexes), followed by a slight increase between 1994-2004 (0.6% in
      men, 1.1% in women), then a further decline until 2008 (annual reduction of 4.4%
      in men, 7.9% in women) (p < 0.05 for all periods). CONCLUSIONS: A decrease in CVD
      mortality was observed from 1995 onwards in Turkey. The causes need to be
      explored in detail to inform future policy priorities in noncommunicable disease
      control.

PMID- 24079270
TI  - Interactions of bacterial cell division protein FtsZ with C8-substituted guanine
      nucleotide inhibitors. A combined NMR, biochemical and molecular modeling
      perspective.
AB  - FtsZ is the key protein of bacterial cell-division and target for new
      antibiotics. Selective inhibition of FtsZ polymerization without impairing the
      assembly of the eukaryotic homologue tubulin was demonstrated with C8-substituted
      guanine nucleotides. By combining NMR techniques with biochemical and molecular
      modeling procedures, we have investigated the molecular recognition of C8
      substituted-nucleotides by FtsZ from Methanococcus jannaschii (Mj-FtsZ) and
      Bacillus subtilis (Bs-FtsZ). STD epitope mapping and trNOESY bioactive
      conformation analysis of each nucleotide were employed to deduce differences in
      their recognition mode by each FtsZ species. GMP binds in the same anti
      conformation as GTP, whereas 8-pyrrolidino-GMP binds in the syn conformation.
      However, the anti conformation of 8-morpholino-GMP is selected by Bs-FtsZ, while
      Mj-FtsZ binds both anti- and syn-geometries. The inhibitory potencies of the C8
      modified-nucleotides on the assembly of Bs-FtsZ, but not of Mj-FtsZ, correlate
      with their binding affinities. Thus, MorphGTP behaves as a nonhydrolyzable analog
      whose binding induces formation of Mj-FtsZ curved filaments, resembling polymers
      formed by the inactive forms of this protein. NMR data, combined with molecular
      modeling protocols, permit explanation of the mechanism of FtsZ assembly
      impairment by C8-substituted GTP analogs. The presence of the C8-substituent
      induces electrostatic remodeling and small structural displacements at the
      association interface between FtsZ monomers to form filaments, leading to
      complete assembly inhibition or to formation of abnormal FtsZ polymers. The
      inhibition of bacterial Bs-FtsZ assembly may be simply explained by steric
      clashes of the C8-GTP-analogs with the incoming FtsZ monomer. This information
      may facilitate the design of antibacterial FtsZ inhibitors replacing GTP. 

PMID- 24079271
TI  - Base pair sensitivity and enhanced ON/OFF ratios of DNA-binding: donor-acceptor
      donor fluorophores.
AB  - The photophysical properties of two recently reported live cell compatible, DNA
      binding dyes, 4,6-bis(4-(4-methylpiperazin-1-yl)phenyl)pyrimidin-2-ol, 1, and
      [1,3-bis[4-(4-methylpiperazin-1-yl)phenyl]-1,3-propandioato-kappaO,
      kappaO']difluoroboron, 2, are characterized. Both dyes are quenched in aqueous
      solutions, while binding to sequences containing only AT pairs enhances the
      emission. Binding of the dyes to sequences containing only GC pairs does not
      produce a significant emission enhancement, and for sequences containing both AT
      and GC base pairs, emission is dependent on the length of the AT pair tracts.
      Through emission lifetime measurements and analysis of the dye redox potentials,
      photoinduced electron transfer with GC pairs is implicated as a quenching
      mechanism. Binding of the dyes to AT-rich regions is accompanied by bathochromic
      shifts of 26 and 30 nm, respectively. Excitation at longer wavelengths thus
      increases the ON/OFF ratio of the bound probes significantly and provides
      improved contrast ratios in solution as well as in fluorescence microscopy of
      living cells. 

PMID- 24079272
TI  - Synthesis and biological evaluation of acyclic phosphonic acid nucleoside
      derivatives.
AB  - As part of a project to generate a library of nucleosides as potential antiviral
      agents, a small subset of novel acyclic phosphonic acid nucleosides was prepared.
      Practical synthetic routes are described for three targets, which were then
      tested against HIV, hepatitis C virus (HCV), and Dengue virus. 

PMID- 24079273
TI  - Antimicrobial evaluation of new synthesized pyridine nucleosides under solvent
      free conditions.
AB  - Two series of novel 3-cyano-2-(2,3,4,6-tetra-O-acetyl-beta-D-glucopyranosyloxo)
      pyridines and 3-cyano-2-(2,3,5-tri-O-acetyl-beta-D-ribofuranosyloxy)-4
      trifluromethyl-6-phenyl pyridine were synthesized using efficient microwave
      methods. The targeted compounds were obtained in high yields by reacting 2-(1H)
      pyridone or its salt with activated sugars using SiO2 under solvent-free
      conditions. Ammonolysis of the resulted acetylated nucleosides produced 3-cyano-2
      (beta-D-glucopyranosyloxo)-pyridines and 3-cyano-2-(beta-D-ribofuranosyloxy)-4
      trifluoromethyl-6-phenyl pyridine. These new products were fully characterized
      using 1D and 2D NMR. These compounds were screened for their antibacterial
      activities against G(+) and G(-) bacteria and some found to exhibit better
      antibacterial activities than the control drug.

PMID- 24079274
TI  - Disaccharide pyrimidine nucleosides and their derivatives: a novel group of cell
      penetrating inhibitors of poly(ADP-ribose) polymerase 1.
AB  - Nearly 30 synthetic nucleosides were tested with human recombinant poly(ADP
      ribose) polymerase 1 as potential inhibitors of this enzyme. The most active
      compounds were some disaccharide analogues of thymidine: 3'-O-beta-D
      ribofuranosyl-5-iodo-dUrd (2d; IC50 = 45 MUM), 3'-O-beta-D-ribofuranosyl-2'
      deoxythymidine (2e; IC50 = 38 MUM), and 3'-O-beta-D-ribofuranosyl-2'
      deoxythymidine oxidized (4; IC50 = 25 MUM). These compounds also reduced H2O2
      induced synthesis of poly(ADP-ribose) in cultured human ovarian carcinoma (SKOV
      3) cells in a dose-dependent manner. Furthermore, compounds 2d or 2e until a
      concentration of 1 mM did not affect growth of SKOV-3 cells, whereas dialdehyde
      compound 4, as well as thymidine, exhibited a significant cytotoxicity.

PMID- 24079275
TI  - Development of Fe/Fe3O4 core-shell nanocubes as a promising magnetic resonance
      imaging contrast agent.
AB  - Here, we report the synthesis, characterization, and properties of Fe/Fe3O4 core
      shell nanocubes prepared via a simple route. It includes NaBH4 reduction of FeCl3
      in an ethylene glycol solution in the presence of 2-mercaptopropionic acid
      (surfactant) and trisodium citrate (cosurfactant) followed by surface oxidation
      with trimethylamine N-oxide. The morphology and structure of Fe/Fe3O4 core-shell
      nanocubes were characterized using transmission electron microscopy (TEM), high
      resolution TEM, selected area electron diffraction, X-ray powder diffraction, and
      X-ray photoelectron spectroscopy. All of the methods confirm a Fe/Fe3O4 core
      shell structure of nanocubes. Magnetic measurements revealed that the Fe/Fe3O4
      core/shell nanocubes are superparamagnetic at 300 K with a saturation
      magnetization of 129 emu/g. The T2 weighted imaging and the T2 relaxation time
      showed high MRI contrast and sensitivity, making these nanocubes viable
      candidates as enhanced MRI contrast agents. 

PMID- 24079276
TI  - Synthesis of 2,3-dihydro-1-phenylbenzo[b]phosphole (1-phenylphosphindane) and its
      use as a mechanistic test in the asymmetric Appel reaction: decisive evidence
      against involvement of pseudorotation in the stereoselecting step.
AB  - Racemic 2,3-dihydro-1-phenylbenzo[b]phosphole was obtained by reduction of 1
      phenylbenzo[b]phosphole-1-oxide, itself derived by ring-closing metathesis of
      phenylstyrylvinylphosphine oxide. The title compound was then reoxidized under
      asymmetric Appel conditions. Comparison of the sense and degree of the
      stereoselectivity to those obtained with an open-chain analogue indicated that
      the ring system does not affect the selectivity of the process. This in turn
      strongly suggests that the stereoselection is not related to pseudorotamer
      preferences in putative phosphorane intermediates. 

PMID- 24079277
TI  - Ba13Si6Sn8As22: a quaternary Zintl phase containing adamantane-like [Si4As10]
      clusters.
AB  - A new quaternary arsenide Zintl phase, Ba13Si6Sn8As22, has been synthesized from
      the Sn-flux reactions, and the structure was determined by the single-crystal X
      ray diffraction methods. The compound crystallizes in the tetragonal non
      centrosymmetric space group I42m (No. 121) with unit cell parameters of a = b =
      14.4857(3) A, c = 13.5506(7) A, V = 2843.40(17) A(3). Its polyanion structure can
      be viewed as composed of [Si4As10] adamantane-like clusters and SiAs4 tetrahedra,
      which are linked via the [Sn2As4] groups built through two edge-sharing SnAs3
      triangular pyramids. Differential thermal analysis and thermogravimetry
      measurements indicate that Ba13Si6Sn8As22 has good thermal stability, and does
      not melt or decompose below 1045 K under Ar atmosphere. Density functional
      calculations were performed on Ba13Si6Sn8As22 and the results suggest a band gap
      of around 1.0 eV for Ba13Si6Sn8As22, confirmed by the diffuse reflectance
      spectrum measurement. In addition, the extensively existing lone pairs of
      electrons on the p-orbitals of As and Sn may also hint interesting nonlinear
      optical properties considering the noncentrosymmetric structure.

PMID- 24079278
TI  - From the editor: The importance of children. Foreword.

PMID- 24079279
TI  - Screening and management of cardiovascular risk factors in children.

PMID- 24079280
TI  - Treatment pattern changes in high-risk patients newly initiated on statin
      monotherapy in a managed care setting.
AB  - BACKGROUND: For high-risk patients who do not achieve guideline-recommended LDL-C
      levels, more intensive treatment including statin-uptitration to higher doses or
      potency, as well as combination therapy may be considered. A better understanding
      of statin treatment patterns in real-world clinical practice may contribute to
      improved lipid-lowering management in these patients. OBJECTIVE: We determined
      treatment pattern changes among patients with high risk of cardiovascular disease
      who were not at low-density lipoprotein cholesterol (LDL-C) goal on statin
      monotherapy. METHODS: Treatment pattern changes were evaluated among patients
      newly initiated on statins between January 1, 2006, and August 31, 2009, in the
      HealthCore Integrated Research Database. Rates and mean time to first and second
      treatment changes were examined in patients with claims for coronary heart
      disease (CHD), atherosclerotic vascular disease (AVD), and diabetes mellitus
      during 12 months before index, who were not at LDL-C <70 mg/dL at their first
      eligible LDL-C test (>= 4 weeks after index). Therapy change was assessed for 12
      months after the LDL-C result. RESULTS: Of 11,473 eligible subjects, 61.3% had
      diabetes, 26.6% had CHD and AVD, and 12.1% had CHD and AVD and diabetes. At
      index, patients were prescribed medium-potency levels of statins, including
      simvastatin (44.7%), atorvastatin (31.5%), and other statins (23.8%). Mean +/- SD
      LDL-C before statin initiation was 138 +/- 34 mg/dL, and at the first-eligible
      LDL-C result after index, it was 101 +/- 25 mg/dL. During follow-up, 7444
      subjects (64.9%) experienced a first treatment change, with mean time to change
      of 93.8 +/- 92 days, whereas 4029 (36.1%) had no treatment change.
      Discontinuation of index therapy occurred in 46.9% of subjects and medication
      switches or titration in 18.0% (index statin titration, switch to other statins,
      other lipid-lowering therapies [LLT], including ezetimibe). Of the discontinuers,
      27.4% restarted LLT. Of subjects with a first treatment change who did not
      discontinue, 48.9% experienced a second therapy change. Results were similar
      between the 3 high-risk groups. CONCLUSIONS: In this managed-care setting, among
      patients with high risk of cardiovascular disease who were not at LDL-C goal,
      statins were usually started at medium-potency doses without being titrated up,
      whereas nearly one-half had a discontinuation of LLT within 12 months. These
      treatment patterns indicate the need for better patient and provider education as
      well as other system-wide modifications to improve medication adherence.

PMID- 24079281
TI  - Design and baseline data of a pediatric study with rosuvastatin in familial
      hypercholesterolemia.
AB  - BACKGROUND: Statin therapy is recommended for children with familial
      hypercholesterolemia (FH), but most children do not reach treatment targets.
      OBJECTIVE: Here we present the design and results at baseline of the ongoing
      CHARON study, to evaluate the safety and efficacy of rosuvastatin. METHODS: This
      study comprises an international 2-year open label, titration-to-goal study in
      198 children with heterozygous FH aged 6 to 18 years, with rosuvastatin in a
      maximum dose of 10 mg (<10 years of age) or 20 mg (older children). In addition,
      64 unaffected siblings were enrolled as controls. The primary efficacy outcome is
      the change from baseline in low-density lipoprotein cholesterol, and the
      secondary outcome is the change in carotid intima-media thickness (c-IMT) in
      patients with FH compared with their siblings. The primary safety outcomes are
      growth and sexual maturation; secondary outcomes are the change in other
      lipoprotein levels and the incidence of adverse events, discontinuation rates,
      and abnormal laboratory values. RESULTS: At baseline, mean age of patients with
      FH was 12.1 +/- 3.3 years, 44% were boys, and mean low-density lipoprotein
      cholesterol levels were 6.1 +/- 1.3 mmol/L (235.9 +/- 48.7 mg/dL). Mean c-IMT was
      0.399 mm (95% CI, 0.392-0.406 mm) in children with FH versus 0.377 (95% CI, 0.366
      0.388 mm) in unaffected siblings (P = .001). CONCLUSIONS: At baseline, as
      expected according to on previous observations, children with FH proved to have a
      greater c-IMT than their healthy siblings. These differences had already occurred
      at a very young age, which emphasizes the importance of considering early statin
      initiation in this high-risk population.

PMID- 24079282
TI  - Differential effects of fenofibrate and extended-release niacin on high-density
      lipoprotein particle size distribution and cholesterol efflux capacity in
      dyslipidemic patients.
AB  - BACKGROUND: The effectiveness of therapies that raise high-density lipoprotein
      cholesterol (HDL-C) to lower cardiovascular disease risk is currently under
      debate, and further research into the relationship between HDL-C and function is
      required. OBJECTIVE: o investigate whether 2 established HDL-C-raising therapies
      had differential effects on parameters of high-density lipoprotein (HDL) quality
      and function, such as HDL particle profile and cholesterol efflux capacity (CEC),
      in patients with dyslipidemia. METHODS AND RESULTS: Sixty-six patients with
      dyslipidemia, 24 with low HDL-C levels (<40 mg/dL) and 42 with normal HDL-C
      levels (40-59 mg/dL), were treated for 6 weeks with fenofibrate (160 mg/d) or
      extended-release (ER) niacin (0.5 g/d for 3 weeks, then 1 g/d) with 4 weeks of
      washout between treatments. Lipoprotein particle size distribution was determined
      using nuclear magnetic resonance, and pathway-specific serum CECs were assessed
      in J774 macrophages, hepatoma, and Chinese hamster ovary-human adenosine
      triphosphate-binding cassette transporter G1 cells. Comparable increases in HDL-C
      and apolipoprotein A-I levels were seen with fenofibrate and ER niacin. There was
      a shift toward larger HDL, predominantly to medium-size HDL particles for
      fenofibrate (+209%) and to large HDL particles for ER niacin (+221%). Minor
      changes in serum CECs were observed with fenofibrate and ER niacin for all the
      efflux pathways measured. Small increases in plasma cholesteryl ester transfer
      protein and lecithin: cholesterol acyltransferase concentrations, and decreases
      in cholesteryl ester transfer protein activity were seen with both drugs.
      CONCLUSIONS: Fenofibrate and ER niacin increased plasma HDL-C level similarly,
      but modulated HDL particle size distribution differently; however, these changes
      did not result in differential effects on serum CECs.

PMID- 24079283
TI  - Effect of colesevelam and niacin on low-density lipoprotein cholesterol and
      glycemic control in subjects with dyslipidemia and impaired fasting glucose.
AB  - BACKGROUND: Niacin monotherapy in patients with dyslipidemia and impaired fasting
      glucose (IFG) may result in hyperglycemia. Colesevelam has the unique dual
      approvals to lower low-density lipoprotein cholesterol (LDL-C) and to improve
      glycemic control in type 2 diabetes mellitus. OBJECTIVES: The aim of our study
      was to evaluate the effect of combined colesevelam and niacin treatment on LDL-C
      lowering and glycemic control in subjects with IFG and dyslipidemia. METHODS: Men
      or women >= 18 years of age, with dyslipidemia (non-high-density lipoprotein
      cholesterol >= 100 mg/dL and <= 220 mg/dL; high-density lipoprotein cholesterol <
      60 mg/dL) and fasting plasma glucose (FPG) >= 90 mg/dL and <= 145 mg/dL were
      randomly assigned 1:1 to colesevelam (3750 mg/d) with niacin titration (n = 70)
      or placebo with niacin titration (n = 70) over 12 weeks. Niacin was titrated from
      500 mg/d up to a maximum of 2000 mg/d as tolerated, and all subjects took enteric
      coated aspirin daily. Lipid and glycemic efficacy parameters were assessed as
      well as safety evaluations of adverse events, vital signs, alanine
      aminotransferase, aspartate aminotransferase, hematology, and urinalysis.
      RESULTS: Adjunct colesevelam had significantly greater LDL-C-lowering effect than
      niacin alone (placebo); -20.67% vs -12.86%, respectively (P = .0088). Niacin
      mediated increases in FPG were significantly less with adjunct colesevelam (1.8
      mg/dL vs 6.7 mg/dL; P = .0046), and fewer colesevelam subjects had increases of
      >= 10 mg/dL in FPG (8 vs 17, respectively). Adjunct colesevelam resulted in
      significantly smaller increases in hemoglobin A1c than placebo (0.06% vs 0.18%,
      respectively; P = .005). Consistent with hemoglobin A1c and FPG changes,
      fructosamine levels significantly decreased with colesevelam treatment (-5.0
      MUmol/L) but increased with placebo (3.0 MUmol/L; P =.0255). CONCLUSIONS:
      Colesevelam as an adjunct to niacin therapy further lowers LDL-C while obviating
      the adverse effects of niacin on glucose metabolism in patients with dyslipidemia
      and IFG.

PMID- 24079284
TI  - Comparative effects of an acute dose of fish oil on omega-3 fatty acid levels in
      red blood cells versus plasma: implications for clinical utility.
AB  - BACKGROUND: Omega-3 fatty acid (n-3 FA) biostatus can be estimated with red blood
      cell (RBC) membranes or plasma. The matrix that exhibits the lower within-person
      variability and is less affected by an acute dose of n-3 FA is preferred in
      clinical practice. OBJECTIVE: We compared the acute effects of a large dose of n
      3 FA on RBC and plasma levels of eicosapentaenoic acid (EPA) plus docosahexaenoic
      acid (DHA). METHODS: Healthy volunteers (n = 20) were given 4 capsules containing
      3.6 g of n-3 FA with a standardized breakfast. Blood samples were drawn at 0, 2,
      4, 6, 8, and 24 hours. The EPA + DHA content of RBC membranes and plasma (the
      latter expressed as a percentage of total FA and as a concentration) were
      determined. General linear mixed models were used to analyze the mean response
      profiles in FA changes over time for plasma and RBCs. RESULTS: At 6 hours after
      load, the plasma concentration of EPA + DHA had increased by 47% (95% confidence
      interval [CI], 24% to 73%) and the plasma EPA + DHA percentage of total FA by 19%
      (95% CI, 4.7% to 36%). The RBC EPA + DHA percentage of composition was unchanged
      [-0.6% (95% CI, -2.6% to 1.5%)]. At 24 hours, the change in both of the plasma
      EPA + DHA markers was 10-fold greater than that in RBCs. CONCLUSIONS: An acute
      dose of n-3 FA (eg, a meal of oily fish or fish oil supplements) taken within a
      day before a doctor's visit can elevate levels of EPA + DHA in plasma, whether
      expressed as a percentage or a concentration, but not in RBC membranes. Similar
      to hemoglobin A1c, which is not affected by an acute glycemic deviation, RBCs
      provide a more reliable estimate of a patient's chronic EPA + DHA status than
      does plasma.

PMID- 24079285
TI  - Lipids and lipoprotein ratios: contribution to carotid intima media thickness in
      adolescents and young adults with type 2 diabetes mellitus.
AB  - BACKGROUND: Dyslipidemia is common among adolescents with type 2 diabetes (T2D).
      OBJECTIVE: To assess whether the lipoprotein ratios of low-density lipoprotein
      (LDL) cholesterol/high-density lipoprotein (HDL) cholesterol or triglycerides/HDL
      or non-HDL cholesterol are more useful than the traditional lipid panel to
      predict increased arterial thickness in adolescents and young adults with T2D.
      METHODS: We evaluated 244 adolescents and young adults with T2D in a cross
      sectional study (mean age 18 years; 56% African American; 65% female).
      Demographics, anthropometrics, and laboratory data were collected. Arterial
      thickness was assessed with carotid intima media thickness (IMT). Bivariate
      correlations and general linear models were used to determine the independent
      contributions of the various lipid parameters to carotid IMT. RESULTS: Bivariate
      correlations showed LDL/HDL ratio was the strongest predictor of carotid IMT (P <
      .02). After adjustment for potential covariates LDL/HDL was no longer
      significant. HDL cholesterol was the only lipid to independently (negatively)
      contribute to carotid IMT. Other risk factors that were independently associated
      with carotid IMT included age, race, sex, body mass index z score, and hemoglobin
      A1c. Together these cardiovascular risk factors explained <20% of the variance in
      carotid IMT. CONCLUSIONS: HDL cholesterol is the only lipid to independently
      associate with carotid IMT. Lipoprotein ratios and non-HDL did not provide
      additional information. The low variance in carotid IMT explained by traditional
      risk factors suggests nontraditional risk factors may be important to assess to
      better understand the contributors to early-stage atherosclerosis in adolescents
      and young adults with T2D.

PMID- 24079286
TI  - The influence of fenofibrate on lipid profile, endothelial dysfunction, and
      inflammatory markers in type 2 diabetes mellitus patients with typical and mixed
      dyslipidemia.
AB  - BACKGROUND: Type 2 diabetes is associated with early development of endothelial
      dysfunction. Patients present with typical dyslipidemia (predominantly high
      levels of triglycerides [TG] and low levels of high-density lipoprotein
      cholesterol [HDL-C]) or mixed hypercholesterolemia (high levels of low-density
      lipoprotein cholesterol [LDL-C] and TG with low HDL-C). Normal levels include LDL
      C < 100 mg/dL, TG < 135 mg/dL, and HDL-C > 40 mg/dL for men and >50 mg/dL for
      women. OBJECTIVE: To determine the effects of 8 weeks' administration of
      fenofibrate on inflammatory markers, metabolic parameters, and endothelial
      dysfunction. METHODS: We administered micronized fenofibrate (Laboratories
      Fourneir S.A Dijon, France) daily for 8 weeks to 40 dyslipidemic, type 2 diabetes
      patients with equal numbers in each arm of the typical or mixed dyslipidemia
      groups. Noninvasive endothelial function assessments were performed and serum
      inflammatory markers obtained before and after treatment. RESULTS: The typical
      group demonstrated significantly greater TG reduction and HDL-C increment, ie,
      56% vs, 21.3% (P < .005) and 21% vs. 7.6% (P = .001), respectively, compared with
      the mixed group. There was greater LDL-C reduction within the mixed group
      compared with the typical group 21.0% vs. 2.2% (P < .05). Endothelial dysfunction
      was present in both groups at baseline. After treatment, the typical group
      demonstrated significant improvement in resting brachial diameter (3.9 mm
      [interquartile range {IQR} 3.3-4.7] to 4.2 mm [IQR 3.4-4.8], P = .001) compared
      with no change within the mixed group (3.6 mm [IQR 3.1-5.4] to 3.7 mm [IQR 3.1
      5.3], P = .26). Flow-mediated diameter improved significantly in both groups. The
      mixed group had significantly greater levels of hs-CRP at baseline but no changes
      throughout the study. The mixed group demonstrated an increase in vascular
      adhesion molecule-1 from 706 ng/mL (IQR 566-1195) to 845 ng/mL (637-1653; P =
      .01), a reduction of tumor necrosis factor-alpha from 7.0 pg/mL (IQR 1.0-43.5) to
      2.5 pg/mL (IQR 1.5-13.5; P = .04) throughout the study. CONCLUSIONS: We
      effectively compared 8 weeks of fenofibrate therapy in type 2 diabetics with
      contrasting lipid abnormalities. The typical dyslipidemia group showed
      significantly greater lipid improvements compared with the mixed dyslipidemia
      group. Both groups had improvements in endothelial functions that were
      independent of the lipid levels. We concluded that fibrate therapy in type 2
      diabetics is beneficial, especially those with typical dyslipidemia and extends
      beyond its lipid lowering properties.

PMID- 24079287
TI  - Relationships between alcohol intake and atherogenic indices in women.
AB  - BACKGROUND: Light-to-moderate alcohol consumption is known to reduce the risk of
      coronary artery disease. OBJECTIVES: The purpose of this study was to investigate
      relationships of alcohol intake with atherogenic indices, such as the ratio of
      low-density lipoprotein cholesterol to high-density lipoprotein cholesterol (LDL
      C/HDL-C ratio) and the ratio of triglycerides to high-density lipoprotein
      cholesterol (TG/HDL-C ratio), in women. METHODS: Subjects (14,067 women, 20-45
      years) were divided by alcohol intake into three groups of nondrinkers,
      occasional drinkers, and regular drinkers, and each drinker group was further
      divided into lower- (<22 g ethanol/drinking day) and greater- (>= 22 g
      ethanol/drinking day) quantity drinkers. Atherogenic indices were compared among
      the alcohol groups. RESULTS: Odds ratio (OR) for high LDL-C/HDL-C ratio or high
      TG/HDL-C ratio calculated after adjustment for age, body mass index, smoking, and
      habitual exercise was significantly lower (P < .05) than a reference level of
      1.00 in regular or occasional lower- and higher quantity drinkers vs. nondrinkers
      (OR for high LDL-C/HDL-C ratio, 0.28 (95% confidence interval [95% CI], 0.18
      0.44) in regular lower-quantity drinkers, 0.18 (95% CI, 0.12-0.28) in regular
      higher quantity drinkers, 0.71 (95% CI, 0.61-0.83) in occasional lower-quantity
      drinkers, and 0.53 (95% CI, 0.44-0.64) in occasional higher quantity drinkers; OR
      for high TG/HDL-C ratio, 0.52 (95% CI, 0.32-0.85) in regular lower-quantity
      drinkers, 0.67 (95% CI, 0.47-0.96) in regular higher-quantity drinkers, 0.61 (95%
      CI, 0.50-0.76) in occasional lower-quantity drinkers, and 0.63 (95% CI, 0.50
      0.79) in occasional higher-quantity drinkers. Both LDL-C/HDL-C ratio and log
      transformed TG/HDL-C ratio were significantly greater in smokers than in
      nonsmokers. Both in smokers and nonsmokers, LDL-C/HDL-C ratio and log-transformed
      TG/HDL-C ratio were significantly lower in regular lower- and higher-quantity
      drinkers than in nondrinkers. In nonsmokers, LDL-C/HDL-C ratio and log
      transformed TG/HDL-C ratio tended to be lower and greater, respectively, in
      regular greater-quantity drinkers than in regular lower-quantity drinkers.
      CONCLUSION: In women, alcohol drinking is inversely associated with atherogenic
      indices irrespective of smoking status, and the inverse association of alcohol
      drinking with LDL-C/HDL-C ratio is stronger than that with TG/HDL-C ratio.

PMID- 24079288
TI  - Effects of carbohydrate restriction and dietary cholesterol provided by eggs on
      clinical risk factors in metabolic syndrome.
AB  - BACKGROUND: There are a limited number of clinical interventions evaluating the
      effects of dietary cholesterol in individuals at elevated risk for type 2
      diabetes and cardiovascular disease. OBJECTIVE: To investigate the effects of
      whole egg intake in adults with metabolic syndrome (MetS). METHODS: Men (n = 12)
      and women (n = 25) with MetS were instructed to follow a moderate carbohydrate
      restricted diet (<30% energy) and randomly assigned to consume either three whole
      eggs (EGG, n = 20) or egg substitute (SUB, n = 17)/d for 12 weeks. Dietary
      intake, MetS parameters, and body composition were assessed at baseline and post
      intervention. RESULTS: Total carbohydrate (P < .001) intake decreased in all
      participants over time. The EGG group consumed more dietary cholesterol (P <
      .001) and choline (P < .001) than the SUB group. MetS was reduced in both groups,
      with improvements noted in dyslipidemia and decreases in waist circumference (P <
      .01), weight (P < .001), and percent body fat (P < .001). Reductions in plasma
      tumor necrosis factor-alpha (P < .001) and serum amyloid A (P < .05) were seen in
      the EGG group only. Notably, increases in dietary cholesterol were associated
      with reductions in plasma tumor necrosis factor-alpha (r = -0.340, P = .04).
      Plasma C-reactive protein, adiponectin, interleukin-6 interleukin-10, and cell
      adhesion molecules were unaffected by the intervention. CONCLUSIONS: These
      results demonstrate that on a moderate carbohydrate background diet, accompanied
      by weight loss, the inclusion of whole eggs improves inflammation to a greater
      extent than yolk-free egg substitute in those with MetS.

PMID- 24079289
TI  - Predictors of statin adherence, switching, and discontinuation in the USAGE
      survey: understanding the use of statins in America and gaps in patient
      education.
AB  - BACKGROUND: Although statins have been shown to reduce cardiovascular disease
      mortality, less than half of U.S. adults achieve their low-density lipoprotein
      cholesterol goal. In many patients initiated on a statin, adherence rates
      decrease over time. OBJECTIVE: To characterize current and former statin users,
      identify reasons for the discontinuation or switching of statins, and identify
      factors associated with adherence. METHODS: The USAGE survey is a cross
      sectional, self-administered Internet-based survey of 10,138 U.S. adults fielded
      September to October 2011. The following statin users were identified and
      compared: adherent nonswitchers, adherent switchers, non-adherent switchers, and
      discontinuers. Univariate and multivariate models using a priori covariates for
      adherence and discontinuation were examined. RESULTS: Most participants were
      current statin users who adhered with their prescribed statin (82.5%, n = 8371).
      Former statin users or discontinuers (12%, n = 1220) cited muscle pain, a side
      effect, as the primary reason for discontinuation (60%), followed by cost (16%),
      and then perceived lack of efficacy (13%). Discontinuers were less satisfied with
      their physicians' explanation of cholesterol treatment, more likely to use the
      Internet to research statins, and less likely to undergo frequent cholesterol
      monitoring. Among adherent statin users, the primary reasons for switching were
      muscle side effects (33%) and cost (32%). Individuals at risk for non-adherence
      included those with low household income, those who experienced muscle pain as a
      side effect while on statin therapy, and those taking medication for
      cardiovascular disease. CONCLUSION: Statin-related muscle side effects are common
      and contribute significantly to rates of discontinuation, switching, and non
      adherence. Improved physician patient communication about side effects and
      benefits of statins are necessary to improve both adherence and outcomes.

PMID- 24079290
TI  - High-density lipoproteins: a consensus statement from the National Lipid
      Association.
AB  - For >4 decades it has been recognized that elevated serum levels of high-density
      lipoprotein cholesterol (HDL-C) are associated with reduced risk of
      cardiovascular disease (CVD) and its sequelae. Many prospective observational
      studies performed around the world have confirmed an inverse relationship between
      HDL-C and cardiovascular risk in people irrespective of sex, race, or ethnicity.
      Consequently, it was assumed that, by extension, raising HDL-C through lifestyle
      modification and pharmacologic intervention would reduce risk of CVD. Animal
      studies are consistent with this assumption. Lipid treatment guidelines around
      the world promoted the recognition of HDL-C as a therapeutic target, especially
      in high-risk patients. Some post hoc analyses from randomized controlled trials
      also suggest that raising HDL-C beneficially affects the risk of CVD. However, a
      number of recent randomized studies putatively designed to test the "HDL
      hypothesis" have failed to show benefit. The results of these trials have caused
      many clinicians to question whether HDL-C is a legitimate therapeutic target. In
      response to the many questions and uncertainties raised by the results of these
      trials, the National Lipid Association convened an expert panel to evaluate the
      current status of HDL-C as a therapeutic target; to review the current state of
      knowledge of HDL particle structure, composition, and function; and to identify
      the salient questions yet to be answered about the role of HDL in either
      preventing or contributing to atherosclerotic disease. The expert panel's
      conclusions and clinical recommendations are summarized herein. The panel
      concludes that, although low HDL-C identifies patients at elevated risk, and much
      investigation suggests that HDL may play a variety of antiatherogenic roles, HDL
      C is not a therapeutic target at the present time. Risk stratified atherogenic
      lipoprotein burden (low-density lipoprotein cholesterol and non-HDL-C) should
      remain the primary and secondary targets of therapy in patients at risk, as
      described by established guidelines. The National Lipid Association emphasizes
      that rigorous research into the biology and clinical significance of low HDL-C
      should continue. The development of novel drugs designed to modulate the serum
      levels and functionality of HDL particles should also continue. On the basis of
      an enormous amount of basic scientific and clinical investigation, a considerable
      number of reasons support the need to continue to investigate the therapeutic
      effect of modulating HDL structure and function. 

PMID- 24079291
TI  - Severe coronary disease in an adult considered at low cardiovascular disease risk
      with a healthy lifestyle.
AB  - Lipoprotein(a) [Lp(a)] is a lipoprotein subclass well-known among the lipid
      community to accelerate atherosclerosis and promote thrombosis through
      incompletely understood mechanism. We report a case of a young man with a healthy
      lifestyle and no major coronary or vascular risk factors who presented to the
      emergency department with an acute coronary syndrome and was ultimately found to
      have severe coronary artery disease. A diagnostic workup revealed elevated Lp(a).
      He was treated with consequent reduction in Lp(a) concentration. This case
      highlights the need to better understand atypical lipoproteins, how they relate
      to cardiovascular disease, the implications for screening family members, and the
      need to standardize patient management guidelines for the purpose of mortality
      risk reduction. 

PMID- 24079292
TI  - Statins do lower cardiovascular mortality.

PMID- 24079293
TI  - Large high-density lipoprotein cholesterol at birth and its early postnatal
      change.

PMID- 24079294
TI  - Response to the letter from Okada et al.

PMID- 24079296
TI  - Probing the failure mechanism of SnO2 nanowires for sodium-ion batteries.
AB  - Nonlithium metals such as sodium have attracted wide attention as a potential
      charge carrying ion for rechargeable batteries. Using in situ transmission
      electron microscopy in combination with density functional theory calculations,
      we probed the structural and chemical evolution of SnO2 nanowire anodes in Na-ion
      batteries and compared them quantitatively with results from Li-ion batteries
      (Huang, J. Y.; et al. Science 2010, 330, 1515 - 1520). Upon Na insertion into
      SnO2, a displacement reaction occurs, leading to the formation of amorphous NaxSn
      nanoparticles dispersed in Na2O matrix. With further Na insertion, the NaxSn
      crystallized into Na15Sn4 (x = 3.75). Upon extraction of Na (desodiation), the
      NaxSn transforms to Sn nanoparticles. Associated with the dealloying, pores are
      found to form, leading to a structure of Sn particles confined in a hollow matrix
      of Na2O. These pores greatly increase electrical impedance, therefore accounting
      for the poor cyclability of SnO2. DFT calculations indicate that Na(+) diffuses
      30 times slower than Li(+) in SnO2, in agreement with in situ TEM measurement.
      Insertion of Na can chemomechanically soften the reaction product to a greater
      extent than in lithiation. Therefore, in contrast to the lithiation of SnO2
      significantly less dislocation plasticity was seen ahead of the sodiation front.
      This direct comparison of the results from Na and Li highlights the critical role
      of ionic size and electronic structure of different ionic species on the
      charge/discharge rate and failure mechanisms in these batteries.

PMID- 24079295
TI  - The PRIME trial protocol: evaluating the impact of an intervention implemented in
      public health centres on management of malaria and health outcomes of children
      using a cluster-randomised design in Tororo, Uganda.
AB  - BACKGROUND: In Africa, inadequate health services contribute to the lack of
      progress on malaria control. Evidence of the impact of interventions to improve
      health services on population-level malaria indicators is needed. We are
      conducting a cluster-randomised trial to assess whether a complex intervention
      delivered at public health centres in Uganda improves health outcomes of children
      and treatment of malaria, as compared to the current standard of care.
      METHODS/DESIGN: Twenty public health centres (level II and III) in Tororo
      district will be included; 10 will be randomly assigned to the intervention and
      10 to control. Clusters will include households located within 2 km of health
      centres. The trial statistician will generate the random allocation sequence and
      assign clusters. Health centres will be stratified by level, and restricted
      randomisation will be employed to ensure balance on cluster location and size.
      Allocation will not be blinded. The intervention includes training in health
      centre management, fever case management with use of rapid diagnostic tests
      (RDTs) for malaria, and patient-centered services, and provision of artemether
      lumefantrine (AL) and RDTs when stocks run low. The impact of the intervention on
      population-level health indicators will be assessed through community surveys
      conducted at baseline in randomly selected children from each cluster, and
      repeated annually for two years. The impact on individuals over time will be
      assessed in a cohort study of children recruited from households randomly
      selected per cluster. The impact on health centres will be assessed using patient
      exit interviews, monthly surveillance, and assessment of health worker knowledge
      and skills. The primary outcome is the prevalence of anaemia (haemoglobin <11.0
      g/dL) in individual children under five measured in the annual community surveys.
      The primary analysis will be based on the cluster-level results. DISCUSSION: The
      PRIME trial findings will be supplemented by the PROCESS study, an evaluation of
      the process, context, and wider impact of the PRIME intervention which will be
      conducted alongside the main trial, together providing evidence of the health
      impact of a public sector intervention in Uganda. TRIAL REGISTRATION AND FUNDING:
      This trial is registered at Clinicaltrials.gov (NCT01024426) and is supported by
      the ACT Consortium.

PMID- 24079297
TI  - Reading people's minds from emotion expressions in interdependent decision
      making.
AB  - How do people make inferences about other people's minds from their emotion
      displays? The ability to infer others' beliefs, desires, and intentions from
      their facial expressions should be especially important in interdependent
      decision making when people make decisions from beliefs about the others'
      intention to cooperate. Five experiments tested the general proposition that
      people follow principles of appraisal when making inferences from emotion
      displays, in context. Experiment 1 revealed that the same emotion display
      produced opposite effects depending on context: When the other was competitive, a
      smile on the other's face evoked a more negative response than when the other was
      cooperative. Experiment 2 revealed that the essential information from emotion
      displays was derived from appraisals (e.g., Is the current state of affairs
      conducive to my goals? Who is to blame for it?); facial displays of emotion had
      the same impact on people's decision making as textual expressions of the
      corresponding appraisals. Experiments 3, 4, and 5 used multiple mediation
      analyses and a causal-chain design: Results supported the proposition that
      beliefs about others' appraisals mediate the effects of emotion displays on
      expectations about others' intentions. We suggest a model based on appraisal
      theories of emotion that posits an inferential mechanism whereby people retrieve,
      from emotion expressions, information about others' appraisals, which then lead
      to inferences about others' mental states. This work has implications for the
      design of algorithms that drive agent behavior in human-agent strategic
      interaction, an emerging domain at the interface of computer science and social
      psychology.

PMID- 24079298
TI  - Attachment anxiety and reactions to relationship threat: the benefits and costs
      of inducing guilt in romantic partners.
AB  - The current research tested whether individuals high in attachment anxiety react
      to relationship threats in ways that can help them feel secure and satisfied in
      their relationship. Individuals higher in attachment anxiety experienced greater
      hurt feelings on days they faced partner criticism or conflict (Study 1) and
      during observed conflict discussions (Study 2). These pronounced hurt feelings
      triggered exaggerated expressions of hurt to induce guilt in the partner.
      Partners perceived the hurt feelings of more anxious individuals to be more
      intense than low anxious individuals' hurt and, in turn, experienced greater
      levels of guilt (Study 1). More anxious individuals were also rated by objective
      coders as exhibiting more guilt-induction strategies during conflict, which led
      to increases in partner guilt (Study 2). Moreover, partner guilt helped anxious
      individuals maintain more positive relationship evaluations. Although greater
      partner guilt had detrimental effects for individuals low in anxiety, more
      anxious individuals experienced more stable perceptions of their partner's
      commitment and more positive relationship evaluations when their partner felt
      more guilt. Unfortunately, these benefits were accompanied by significant
      declines in the partner's relationship satisfaction. These results illustrate
      that anxious reactions to threat are not uniformly destructive; instead, the
      reassuring emotions their reactions induce in relationship partners help anxious
      individuals feel satisfied and secure in their partner's commitment.

PMID- 24079300
TI  - Selenium fertilization alters the chemical composition and antioxidant
      constituents of tomato (Solanum lycopersicon L.).
AB  - Although selenium (Se) is a known anticarcinogen, little is known regarding how
      Se affects other nutritional qualities in crops. Tomato ( Solanum lycopersicon )
      was supplied with 0-50 MUM selenate and analyzed for elemental composition and
      antioxidant compounds. When supplied at low doses (5 and 10 MUM) via the roots,
      Se stimulated the synthesis of phenolic compounds in leaves and reduced the
      levels of Mo, Fe, Mn, and Cu in roots. At higher doses (25 and 50 MUM Se) leaf
      glutathione levels were 3-5-fold enhanced. Supply of selenate via foliar spray
      (0, 2, or 20 mg Se plant(-1)) resulted in Se-biofortified tomato fruits, with Se
      levels low enough not to pose a health risk. The Se-biofortified fruits showed
      enhanced levels of the antioxidant flavonoids naringenin chalcone and kaempferol
      and a concomitant decrease of cinnamic acid derivatives. Thus, tomato fruits can
      be safely enriched with Se, and Se biofortification may enhance levels of other
      neutraceutical compounds. 

PMID- 24079299
TI  - Understanding the sequential activation of Type III and Type VI Secretion Systems
      in Salmonella typhimurium using Boolean modeling.
AB  - BACKGROUND: Three pathogenicity islands, viz. SPI-1 (Salmonella pathogenicity
      island 1), SPI-2 (Salmonella pathogenicity island 2) and T6SS (Type VI Secretion
      System), present in the genome of Salmonella typhimurium have been implicated in
      the virulence of the pathogen. While the regulation of SPI-1 and SPI-2 (both
      encoding components of the Type III Secretion System - T3SS) are well understood,
      T6SS regulation is comparatively less studied. Interestingly, inter-connections
      among the regulatory elements of these three virulence determinants have also
      been suggested to be essential for successful infection. However, till date, an
      integrated view of gene regulation involving the regulators of these three
      secretion systems and their cross-talk is not available. RESULTS: In the current
      study, relevant regulatory information available from literature have been
      integrated into a single Boolean network, which portrays the dynamics of T3SS
      (SPI-1 and SPI-2) and T6SS mediated virulence. Some additional regulatory
      interactions involving a two-component system response regulator YfhA have also
      been predicted and included in the Boolean network. These predictions are aimed
      at deciphering the effects of osmolarity on T6SS regulation, an aspect that has
      been suggested in earlier studies, but the mechanism of which was hitherto
      unknown. Simulation of the regulatory network was able to recreate in silico the
      experimentally observed sequential activation of SPI-1, SPI-2 and T6SS.
      CONCLUSIONS: The present study integrates relevant gene regulatory data (from
      literature and our prediction) into a single network, representing the cross
      communication between T3SS (SPI-1 and SPI-2) and T6SS. This holistic view of
      regulatory interactions is expected to improve the current understanding of
      pathogenesis of S. typhimurium.

PMID- 24079301
TI  - Effect of health insurance on the utilisation of allied health services by people
      with chronic disease: a systematic review and meta-analysis.
AB  - Allied health services benefit the management of many chronic diseases. The
      effects of health insurance on the utilisation of allied health services has not
      yet been established despite health insurance frequently being identified as a
      factor promoting utilisation of medical and hospital services among people with
      chronic disease. The objective of this systematic review and meta-analysis was to
      establish the effects of health insurance on the utilisation of allied health
      services by people with chronic disease. Medline (Ovid Medline 1948 to Present
      with Daily Update), EMBASE (1980 to 1 April 2011), CINAHL, PsychINFO and the
      Cochrane Central Register of Controlled Trials were searched to 12 April 2011
      inclusive. Studies were eligible for inclusion if they were published in English,
      randomised controlled trials, quasi-experimental trials, quantitative
      observational studies and included people with one or more chronic diseases using
      allied health services and health insurance. A full-text review was performed
      independently by two reviewers. Meta-analyses were conducted. One hundred and
      fifty-eight citations were retrieved and seven articles were included in the meta
      analyses. The pooled odds ratio (95% CI) of having insurance (versus no
      insurance) on the utilisation of allied health services among people with chronic
      disease was 1.33 (1.16-1.52; P<0.001). There was a significant effect of
      insurance on the utilisation of non-physiotherapy services, pooled odds ratio
      (95% CI) 4.80 (1.46-15.79; P=0.01) but having insurance compared with insurance
      of a lesser coverage was not significantly associated with an increase in
      physiotherapy utilisation, pooled odds ratio (95% CI) 1.53 (0.81-2.91; P=0.19).
      The presence of co-morbidity or functional limitation and higher levels of
      education increased utilisation whereas gender, race, marital status and income
      had a limited and variable effect, according to the study population. The review
      was limited by the considerable heterogeneity in the research questions being
      asked, sample sizes, study methodology (including allied health service),
      insurance type and dependent variables analysed. The presence of health insurance
      was generally associated with increased utilisation of allied health services;
      however, this varied depending on the population, provider type and insurance
      product. 

PMID- 24079302
TI  - Synthesising practice guidelines for the development of community-based exercise
      programmes after stroke.
AB  - BACKGROUND: Multiple guidelines are often available to inform practice in complex
      interventions. Guidance implementation may be facilitated if it is tailored to
      particular clinical issues and contexts. It should also aim to specify all
      elements of interventions that may mediate and modify effectiveness, including
      both their content and delivery. We conducted a focused synthesis of
      recommendations from stroke practice guidelines to produce a structured and
      comprehensive account to facilitate the development of community-based exercise
      programmes after stroke. METHODS: Published stroke clinical practice guidelines
      were searched for recommendations relevant to the content and delivery of
      community-based exercise interventions after stroke. These were synthesised using
      a framework based on target intervention outcomes, personal and programme
      proximal objectives, and recommended strategies. RESULTS: Nineteen guidelines
      were included in the synthesis (STRIDES; STroke Rehabilitation Intervention
      Development Evidence Synthesis). Eight target outcomes, 14 proximal objectives,
      and 94 recommended strategies were identified. The synthesis was structured to
      present best practice recommendations in a format that could be used by
      intervention programme developers. It addresses both programme content and
      context, including personal factors, service standards and delivery issues. Some
      recommendations relating to content, and many relating to delivery and other
      contextual issues, were based on low level evidence or expert opinion. Where
      opinion varied, the synthesis indicates the range of best practice options
      suggested in guidelines. CONCLUSIONS: The synthesis may assist implementation of
      best practice by providing a structured intervention description that focuses on
      a particular clinical application, addresses practical issues involved in
      programme development and provision, and illustrates the range of best-practice
      options available to users where robust evidence is lacking. The synthesis
      approach could be applied to other areas of stroke rehabilitation or to other
      complex interventions.

PMID- 24079303
TI  - Multi-criteria decision analysis as an innovative approach to managing zoonoses:
      results from a study on Lyme disease in Canada.
AB  - BACKGROUND: Zoonoses are a growing international threat interacting at the human
      animal-environment interface and call for transdisciplinary and multi-sectoral
      approaches in order to achieve effective disease management. The recent emergence
      of Lyme disease in Quebec, Canada is a good example of a complex health issue for
      which the public health sector must find protective interventions. Traditional
      preventive and control interventions can have important environmental, social and
      economic impacts and as a result, decision-making requires a systems approach
      capable of integrating these multiple aspects of interventions. This paper
      presents the results from a study of a multi-criteria decision analysis (MCDA)
      approach for the management of Lyme disease in Quebec, Canada. MCDA methods allow
      a comparison of interventions or alternatives based on multiple criteria.
      METHODS: MCDA models were developed to assess various prevention and control
      decision criteria pertinent to a comprehensive management of Lyme disease: a
      first model was developed for surveillance interventions and a second was
      developed for control interventions. Multi-criteria analyses were conducted under
      two epidemiological scenarios: a disease emergence scenario and an epidemic
      scenario. RESULTS: In general, we observed a good level of agreement between
      stakeholders. For the surveillance model, the three preferred interventions were:
      active surveillance of vectors by flagging or dragging, active surveillance of
      vectors by trapping of small rodents and passive surveillance of vectors of human
      origin. For the control interventions model, basic preventive communications,
      human vaccination and small scale landscaping were the three preferred
      interventions. Scenarios were found to only have a small effect on the group
      ranking of interventions in the control model. CONCLUSIONS: MCDA was used to
      structure key decision criteria and capture the complexity of Lyme disease
      management. This facilitated the identification of gaps in the scientific
      literature and enabled a clear identification of complementary interventions that
      could be used to improve the relevance and acceptability of proposed prevention
      and control strategy. Overall, MCDA presents itself as an interesting systematic
      approach for public health planning and zoonoses management with a "One Health"
      perspective.

PMID- 24079304
TI  - Identification and fine-mapping of a QTL, qMrdd1, that confers recessive
      resistance to maize rough dwarf disease.
AB  - BACKGROUND: Maize rough dwarf disease (MRDD) is a devastating viral disease that
      results in considerable yield losses worldwide. Three major strains of virus
      cause MRDD, including maize rough dwarf virus in Europe, Mal de Rio Cuarto virus
      in South America, and rice black-streaked dwarf virus in East Asia. These viral
      pathogens belong to the genus fijivirus in the family Reoviridae. Resistance
      against MRDD is a complex trait that involves a number of quantitative trait loci
      (QTL). The primary approach used to minimize yield losses from these viruses is
      to breed and deploy resistant maize hybrids. RESULTS: Of the 50 heterogeneous
      inbred families (HIFs), 24 showed consistent responses to MRDD across different
      years and locations, in which 9 were resistant and 15 were susceptible. We
      performed trait-marker association analysis on the 24 HIFs and found six
      chromosomal regions which were putatively associated with MRDD resistance. We
      then conducted QTL analysis and detected a major resistance QTL, qMrdd1, on
      chromosome 8. By applying recombinant-derived progeny testing to self-pollinated
      backcrossed families, we fine-mapped the qMrdd1 locus into a 1.2-Mb region
      flanked by markers M103-4 and M105-3. The qMrdd1 locus acted in a recessive
      manner to reduce the disease-severity index (DSI) by 24.2-39.3%. The genetic
      effect of qMrdd1 was validated using another F6 recombinant inbred line (RIL)
      population in which MRDD resistance was segregating and two genotypes at the
      qMrdd1 locus differed significantly in DSI values. CONCLUSIONS: The qMrdd1 locus
      is a major resistance QTL, acting in a recessive manner to increase maize
      resistance to MRDD. We mapped qMrdd1 to a 1.2-Mb region, which will enable the
      introgression of qMrdd1-based resistance into elite maize hybrids and reduce MRDD
      related crop losses.

PMID- 24079305
TI  - Introduction of the community first responder system into Japan: is that
      possible?
AB  - BACKGROUND: To improve out-of-hospital cardiac arrest (OHCA) survival rates in
      Japan, implementation of a community first responder (CFR) system is considered
      one of the most effective emergency medical service options. We investigated the
      possibility of introducing a CFR system in Japan. METHODS: Cross-sectional
      surveys were given to 1,350 residents over the age of 18 who were selected from
      resident registration lists in Tochigi prefecture. Residents were questioned
      whether they would agree to have a CFR system in their community and whether they
      would participate as a responder. Positive attitudes about the cross-sectional
      study led us to conduct pilot CFR trials. Trials were conducted in rural areas of
      Tochigi prefecture by local EMS personnel. We were able to discuss and develop
      CFR introduction guidelines for Japanese communities using the results of the
      individual surveys, pilot trials, and other countries' guidelines. Finally, our
      CFR system, which referred to developed CFR introduction guidelines, was
      introduced into Ishikawa prefecture's Shioya town (population of 710). RESULTS: A
      total of 92.5% of Tochigi residents either strongly agreed or agreed to have a
      CFR system in their community, and 16.7% of Tochigi's residents chose to
      participate. The two CFR introduction prerequisites were identified as: (1) an
      information delivery system for CFR and (2) budget preparation. CFR introduction
      guidelines were developed, and a CFR system was introduced in Shioya town on 4
      November 2012 with 32 participants. On 1 January 2013, a CFR responded for the
      first time, and the CFR system worked efficiently. CONCLUSIONS: By providing
      information about the CFR system to the community and preparing several
      infrastructural elements, it was possible to introduce and operate a successful
      CFR system in Japan.

PMID- 24079307
TI  - Unfalsifiability and mutual translatability of major modeling schemes for choice
      reaction time.
AB  - [Correction Notice: An Erratum for this article was reported in Vol 121(1) of
      Psychological Review (see record 2014-03591-005). The link to supplemental
      material was missing. All versions of this article have been corrected.] Much
      current research on speeded choice utilizes models in which the response is
      triggered by a stochastic process crossing a deterministic threshold. This
      article focuses on 2 such model classes, 1 based on continuous-time diffusion and
      the other on linear ballistic accumulation (LBA). Both models assume random
      variability in growth rates and in other model components across trials. We show
      that if the form of this variability is unconstrained, the models can exactly
      match any possible pattern of response probabilities and response time
      distributions. Thus, the explanatory or predictive content of these models is
      determined not by their structural assumptions but, rather, by distributional
      assumptions (e.g., Gaussian distributions) that are traditionally regarded as
      implementation details. Selective influence assumptions (i.e., which experimental
      manipulations affect which model parameters) are shown to have no restrictive
      effect, except for the theoretically questionable assumption that speed-accuracy
      instructions do not affect growth rates. The 2nd contribution of this article
      concerns translation of falsifiable models between universal modeling languages.
      Specifically, we translate the predictions of the diffusion and LBA models (with
      their parametric and selective influence assumptions intact) into the Grice
      modeling framework, in which accumulation processes are deterministic and
      thresholds are random variables. The Grice framework is also known to reproduce
      any possible pattern of response probabilities and times, and hence it can be
      used as a common language for comparing models. It is found that only a few
      simple properties of empirical data are necessary predictions of the diffusion
      and LBA models.

PMID- 24079306
TI  - Usefulness of Plasmodium falciparum-specific rapid diagnostic tests for
      assessment of parasite clearance and detection of recurrent infections after
      artemisinin-based combination therapy.
AB  - BACKGROUND: Rapid diagnostic test (RDT) is an important tool for parasite-based
      malaria diagnosis. High specificity of RDTs to distinguish an active Plasmodium
      falciparum infection from residual antigens from a previous infection is crucial
      in endemic areas where residents are repeatedly exposed to malaria. The
      efficiency of two RDTs based on histidine-rich protein 2 (HRP2) and lactate
      dehydrogenase (LDH) antigens were studied and compared with two microscopy
      techniques (Giemsa and acridine orange-stained blood smears) and real-time
      polymerase chain reaction (PCR) for assessment of initial clearance and detection
      of recurrent P. falciparum infections after artemisinin-based combination therapy
      (ACT) in a moderately high endemic area of rural Tanzania. METHODS: In this
      exploratory study 53 children < five years with uncomplicated P. falciparum
      malaria infection were followed up on nine occasions, i.e., day 1, 2, 3, 7, 14,
      21, 28, 35 and 42, after initiation of artemether-lumefantrine treatment. At each
      visit capillary blood samples was collected for the HRP2 and LDH-based RDTs,
      Giemsa and acridine orange-stained blood smears for microscopy and real-time PCR.
      Assessment of clearance times and detection of recurrent P. falciparum infections
      were done for all diagnostic methods. RESULTS: The median clearance times were 28
      (range seven to >42) and seven (two to 14) days for HRP2 and LDH-based RDTs, two
      (one to seven) and two (one to 14) days for Giemsa and acridine orange-stained
      blood smear and two (one to 28) days for real-time PCR. RDT specificity against
      Giemsa-stained blood smear microscopy was 21% for HRP2 on day 14, reaching 87% on
      day 42, and >=96% from day 14 to 42 for LDH. There was no significant correlation
      between parasite density at enrolment and duration of HRP2 positivity (r = 0.13,
      p = 0.34). Recurrent malaria infections occurred in ten (19%) children. The HRP2
      and LDH-based RDTs did not detect eight and two of the recurrent infections,
      respectively. CONCLUSION: The LDH-based RDT was superior to HRP2-based for
      monitoring of treatment outcome and detection of recurrent infections after ACT
      in this moderately high transmission setting. The results may have implications
      for the choice of RDT devices in similar transmission settings for improved
      malaria case management. TRIAL REGISTRATION: Clinicaltrials.gov, NCT01843764.

PMID- 24079308
TI  - A new bixanthone derivative from the bark of Garcinia oblongifolia.
AB  - A new bixanthone derivative, garciobioxanthone (1), was isolated from the EtOH
      extract of the bark of Garcinia oblongifolia, together with 11 known compounds.
      The structure of 1 was elucidated on the basis of 1D NMR, 2D NMR and other
      spectroscopic analysis. The structures of the known compounds were identified by
      comparison of their spectroscopic data with those reported in the references. 

PMID- 24079309
TI  - Resurrecting the ecological underpinnings of ocean plankton blooms.
AB  - Nutrient and light conditions control phytoplankton division rates in the surface
      ocean and, it is commonly believed, dictate when and where high concentrations,
      or blooms, of plankton occur. Yet after a century of investigation, rates of
      phytoplankton biomass accumulation show no correlation with cell division rates.
      Consequently, factors controlling plankton blooms remain highly controversial. In
      this review, we endorse the view that blooms are not governed by abiotic factors
      controlling cell division, but rather reflect subtle ecosystem imbalances
      instigated by climate forcings or food-web shifts. The annual global procession
      of ocean plankton blooms thus represents a report on the recent history of
      predator-prey interactions modulated by physical processes that, almost
      coincidentally, also control surface nutrient inputs. 

PMID- 24079318
TI  - [The new ICMJE recommendations].

PMID- 24079310
TI  - The parallel lives of alpha1-antitrypsin deficiency and pulmonary alveolar
      proteinosis.
AB  - In 1963, five cases of alpha1-antitrypsin deficiency were reported in the
      scientific literature, as well as an attempt to treat pulmonary alveolar
      proteinosis by a massive washing of the lung (whole lung lavage). Now, fifty
      years later, it seems the ideal moment not only to commemorate these
      publications, but also to point out the influence both papers had in the
      following decades and how knowledge on these two fascinating rare respiratory
      disorders progressed over the years. This paper is therefore not aimed at being a
      comprehensive review for both disorders, but rather at comparing the evolution of
      alpha1-antitrypsin, a rare disorder, with that of pulmonary alveolar proteinosis,
      an ultra-rare disease. We wanted to emphasize how all stakeholders might
      contribute to the dissemination of the awareness of rare diseases, that need to
      be chaperoned from the ghetto of neglected disorders to the dignity of
      recognizable and treatable disorders. 

PMID- 24079319
TI  - [The seven CanMEDS roles in postgraduate medical education should be kept, but
      revised].

PMID- 24079320
TI  - [The seven CanMEDS roles in postgraduate medical education should be revised].
AB  - The seven CanMEDS roles were adopted by the Danish reform in postgraduate medical
      education in 2004. The roles have become a natural part of defining specialist
      competence. However, the definition of the seven roles from 2000 might not be
      aligned with the perception of good medical practice anno 2013. It is recommended
      to redefine the seven roles to reach agreement with contemporary demands for
      specialist competence. 

PMID- 24079321
TI  - [New endocrine treatments prolong survival of patients with castration-resistant
      prostate cancer].
AB  - Prostate cancer that progresses despite castrate levels of serum testosterone is
      defined as castration-resistant prostate cancer (CRPC). Molecular investigations
      of the disease have established that progression of CRPC remains driven by
      androgen receptor signalling and that CRPC continues to respond to hormonal
      manipulation. Recently, new endocrine treatments including an androgen receptor
      signalling inhibitor and a testosterone synthesis inhibitor have been approved
      for treatment of CRPC. We review the pivotal phase 3 trials and discuss their
      implications for future treatment of CRPC. 

PMID- 24079322
TI  - [Clinical use of estimated glomerular filtration rate for evaluation of kidney
      function].
AB  - Estimating glomerular filtration rate by the Modification of Diet in Renal
      Disease or Chronic Kidney Disease Epidemiology Collaboration formulas gives a
      reasonable estimate of kidney function for e.g. classification of chronic kidney
      disease. Additionally the estimated glomerular filtration rate is a significant
      predictor for cardiovascular disease and may along with classical cardiovascular
      risk factors add useful information to risk estimation. Several cautions need to
      be taken into account, e.g. rapid changes in kidney function, dialysis, high age,
      obesity, underweight and diverging and unanticipated deviations in muscle mass
      may make the estimate unreliable. 

PMID- 24079323
TI  - [Pulmonary stethoscopy].

PMID- 24079324
TI  - [Onychomycosis is rare in young children, and treatment is a task for
      dermatological specialists].
AB  - Onychomycosis was diagnosed in a two-year-old girl. The infection was caused by
      Trichophyton rubrum, which is the most frequent cause of toenail onychomycosis.
      The diagnosis was confirmed by polymerase chain reaction, microscopy and culture.
      She was treated with orally given terbinafine and topically given amorolfine with
      clinical improvement at the following control visit. Onychomycosis is rare in
      children, but the occurrence seems to be increasing. Medical treatment can be
      topical, systemic or a combination of these. 

PMID- 24079325
TI  - Recommendations for a uniform assessment of publication bias related to funding
      source.
AB  - BACKGROUND: Numerous studies on publication bias in clinical drug research have
      been undertaken, particularly on the association between sponsorship and
      favourable outcomes. However, no standardized methodology for the classification
      of outcomes and sponsorship has been described. Dissimilarities and ambiguities
      in this assessment impede the ability to compare and summarize results of studies
      on publication bias. To guide authors undertaking such studies, this paper
      provides recommendations for a uniform assessment of publication bias related to
      funding source. METHODS AND RESULTS: As part of ongoing research into publication
      bias, 472 manuscripts on randomised controlled trials (RCTs) with drugs,
      submitted to eight medical journals from January 2010 through April 2012, were
      reviewed. Information on trial results and sponsorship was extracted from
      manuscripts. During the start of this evaluation, several problems related to the
      classification of outcomes, inclusion of post-hoc analyses and follow-up studies
      of RCTs in the study sample, and assessment of the role of the funding source
      were encountered. A comprehensive list of recommendations addressing these
      problems was composed. To assess internal validity, reliability and usability of
      these recommendations were tested through evaluation of manuscripts submitted to
      journals included in our study. CONCLUSIONS: The proposed recommendations
      represent a first step towards a uniform method of classifying trial outcomes and
      sponsorship. This is essential to draw valid conclusions on the role of the
      funding source in publication bias and will ensure consistency across future
      studies.

PMID- 24079326
TI  - Superconducting filaments formed during nonvolatile resistance switching in
      electrodeposited delta-Bi(2)O(3).
AB  - We show that electrodeposited films of delta-Bi2O3 in a Pt/delta-Bi2O3/Au cell
      exhibit unipolar resistance switching. After being formed at a large electric
      field of 40 MV/m, the cell can be reversibly switched between a low resistance
      state (156 Omega) and a high resistance state (1.2 GOmega) by simply cycling
      between SET and RESET voltages of the same polarity. Because the high and low
      resistance states are persistent, the cell is a candidate for nonvolatile
      resistance random access memory (RRAM). A Bi nanofilament forms at the SET
      voltage, and it ruptures to form a 50 nm gap during the RESET step at a current
      density of 2 * 10(7) A/cm(2). The diameter of the Bi filament is a function of
      the compliance current, and can be tuned from 140 to 260 nm, but the current
      density in the RESET step is independent of the Bi diameter. An electromigration
      rupture mechanism is proposed. The Bi nanofilaments in the low resistance state
      are superconducting, with a Tc of 5.8 K and an Hc of 5 kOe. This is an unexpected
      result, because bulk Bi is not a superconductor. 

PMID- 24079327
TI  - Tumor targeting effects of a novel modified paclitaxel-loaded discoidal mimic
      high density lipoproteins.
AB  - OBJECTIVE: Monocholesterylsuccinate (CHS)-modified paclitaxel-loaded discoidal
      reconstituted high density lipoproteins (cP-d-rHDL) as novel biomimetic
      nanocarriers that were developed for tumor targeting delivery to avoid unexpected
      drug leakage from discoidal reconstituted high density lipoproteins (d-rHDL)
      during remodeling process associated with lecithin-cholesterol acyltransferase
      (LCAT). METHODS: Their in vitro characterizations and biomimetic properties,
      simultaneously tumor distribution and pharmacodynamics in tumor bearing mice were
      elaborately investigated. RESULTS: In vitro characterization results showed that
      cP-d-rHDL had nano-size diameter, high negative zeta potential and high
      entrapment efficiency (EE). Furthermore, morphology study indicated that cP-d
      rHDL did not remodel in the presence of LCAT, compared with that of paclitaxel
      loaded d-rHDL (P-d-rHDL, not modified). And cellular uptake, together with
      cytotoxicity toward tumor cells of cP-d-rHDL was not affected after interaction
      with LCAT. Tumor distribution and pharmacodynamics tests revealed that cP-d-rHDL
      possessed specific targeting property and anti-tumor efficacy. CONCLUSION: cP-d
      rHDL served to restrain remodeling process and drug leakage, at the same time
      reinforce the targeting effect, and could act as a potential drug delivery system
      for cancer therapy.

PMID- 24079329
TI  - Trends in added sugar supply and consumption in Australia: there is an Australian
      Paradox.
AB  - In 2011, Barclay and Brand-Miller reported the observation that trends in refined
      sugar consumption in Australia were the inverse of trends in overweight and
      obesity (The Australian Paradox). Rikkers et al. claim that the Australian
      Paradox is based on incomplete data because the sources utilised did not
      incorporate estimates for imported processed foods. This assertion is incorrect.
      Indeed, national nutrition surveys, sugar consumption data from the United
      Nations Food and Agricultural Organisation, the Australian Bureau of Statistics
      and Australian beverage industry data all incorporated data on imported products.

PMID- 24079328
TI  - Cytochrome p450sky interacts directly with the nonribosomal peptide synthetase to
      generate three amino acid precursors in skyllamycin biosynthesis.
AB  - The generation of modified amino acid precursors for incorporation in
      nonribosomal peptide synthesis (NRPS) plays a crucial, if often understated, role
      in the generation of peptide natural products. The biosynthesis of the cyclic
      depsipeptide skyllamycin requires three beta-hydroxylated amino acid precursors,
      with in vivo gene inactivation experiments implicating cytochrome P450sky
      (CYP163B3) in the hydroxylation of these amino acids. Here, we demonstrate the in
      vitro oxidation of l-amino acid substrates bound to peptidyl carrier protein
      (PCP) domains 5, 7, and 11 of the skyllamycin nonribosomal synthetase by P450sky.
      Selectivity for these domains over other PCP domains could be demonstrated, with
      hydroxylation selective for l-amino acids and stereospecific in nature resulting
      in the (2S,3S)-configuration. The oxidation of amino acids or small molecule
      substrate analogues was not supported, demonstrating the necessity of the carrier
      protein in P450sky-catalyzed hydroxylation. The binding of aminoacyl-PCP
      substrates to P450sky was detected for the catalytically active PCP7 but not for
      the catalytically inactive PCP10, indicating carrier protein-mediated selectivity
      in P450sky substrate binding. X-ray crystal structures of P450sky reveal a 3D
      structure with a highly open active site, the size of which is dictated by the
      carrier protein bound nature of the substrate. P450sky is the first P450
      demonstrated to not only interact directly with PCP-bound amino acids within the
      peptide-forming NRPS but also to do so with three different PCP domains in a
      specific fashion. This represents an expansion of the complexity and scope of
      NRPS-mediated peptide synthesis, with the generation of hydroxylated amino acid
      precursors occurring through the interaction of P450 enzymes following, rather
      than prior to, the selection of amino acids by NRPS-adenylation domains. 

PMID- 24079330
TI  - Solid phase extraction of N-linked glycopeptides using hydrazide tip.
AB  - Glycoproteome contains valuable information where biomarkers may be discovered
      for disease diagnosis and monitoring. Nowadays, with the ever-increasing
      performances of mass spectrometers, the emphasis is shifting to the sample
      preparation for better throughput and reproducibility. Therefore, to facilitate
      high throughput N-linked glycopeptide isolation, in this study, a novel hydrazide
      tip was devised and an integrated workflow of N-linked glycopeptide isolation
      using hydrazide tips was presented. With the use of bovine fetuin as a standard
      glycoprotein, the incubation time was determined for each major step of
      glycopeptide isolation. With the use of commercially available human serum,
      multiple parallel isolations of glycopeptides were performed using hydrazide tips
      with a liquid handling robotic system. We demonstrated that, with the hydrazide
      tips, the processing time was significantly decreased from 3 to 4 days to less
      than 8 h with excellent reproducibility. The hydrazide pipet tips have great
      potential in achieving automation of N-linked glycopeptide isolation for high
      throughput sample preparation when used in combination with liquid handling
      robotic systems. 

PMID- 24079331
TI  - In situ formed Si nanoparticle network with micron-sized Si particles for lithium
      ion battery anodes.
AB  - To address the significant challenges associated with large volume change of
      micrometer-sized Si particles as high-capacity anode materials for lithium-ion
      batteries, we demonstrated a simple but effective strategy: using Si
      nanoparticles as a structural and conductive additive, with micrometer-sized Si
      as the main lithium-ion storage material. The Si nanoparticles connected into the
      network structure in situ during the charge process, to provide electronic
      connectivity and structure stability for the electrode. The resulting electrode
      showed a high specific capacity of 2500 mAh/g after 30 cycles with high initial
      Coulombic efficiency (73%) and good rate performance during electrochemical
      lithiation and delithiation: between 0.01 and 1 V vs Li/Li(+). 

PMID- 24079332
TI  - Toward generating low-friction nanoengineered surfaces with liquid-vapor
      interfaces.
AB  - Using molecular dynamics (MD), we investigate the importance of liquid-vapor
      interface topography in designing low-friction nanoengineered superhydrophobic
      surfaces. Shear flow is simulated on patterned surfaces. The relationship between
      the effective slip length and bubble meniscus curvature is attained by generating
      entrapped bubbles with large protrusion angles on patterned surfaces with
      nanoholes. We show that protruding bubbles can induce significant friction, which
      hinders the slip characteristics produced on liquid-vapor interfaces. By
      comparing surfaces with nanoholes and nanopillars, we also demonstrate that the
      continuity of the liquid-vapor interface can greatly influence slip. Our MD
      results yield an asymptotic behavior of slip length with varying gas fractions,
      which are found to be consistent with observations from simulations and
      analytical models produced in continuum studies. 

PMID- 24079334
TI  - Semen quality evaluation in a cohort of 28213 adult males from Sichuan area of
      south-west China.
AB  - The trends in semen quality are conflicting. Although many previous surveys on
      semen quality indicated a decline, the trends in semen quality in Sichuan area of
      south-west China are not clear. We analysed the semen parameters in a cohort of
      28,213 adult males close to general population in Sichuan between July 2007 and
      June 2012, and investigated the changes on semen quality. The semen parameters
      including pH, volume, concentration, motility, morphology were measured according
      to the World Health Organization (WHO) criteria. Kruskal-Wallis analysis of
      variance was used to examine the statistical differences of semen quality between
      groups. We found that the medians (5th and 95th percentiles) were 2.4 ml (1.0
      5.0) for semen volume, 62.0 * 10(6) ml(-1) (15.0-142.0) for semen concentration,
      39% (18-60%) for sperm progressive motility and 10.5% (1.0-34.5%) for normal
      morphology. In these 5 years, sperm concentration and the percentage of sperm
      normal morphology were decreased from 66.0 * 10(6 ) ml(-1) to 49.0 * 10(6) ml(-1)
      and from 13.5% to 4.5%, respectively; among different reproductive history
      groups, sperm concentration and the percentage of sperm normal morphology were
      also decreased in these 5 years. And the incidence of azoospermia was increasing.
      These may imply that there is a decline in semen quality of adult males in
      Sichuan area.

PMID- 24079333
TI  - Maintaining the unmethylated state.
AB  - BACKGROUND: A remarkable correspondence exists between the cytogenetic locations
      of the known fragile sites and frequently reported sites of hypermethylation. The
      best-known features of fragile sites are sequence motifs that are prone to the
      spontaneous formation of a non-B DNA structure. These facts, coupled with the
      known enzymological specificities of DNA methyltransferase 1 (DNMT1), the ATP
      dependent and actin-dependent helicases, and the ten-eleven translocation (TET)
      dioxygenases, suggest that these enzymes are involved in an epigenetic cycle that
      maintains the unmethylated state at these sites by resolving non-B structure,
      preventing both the sequestration of DNA methyltransferases (DNMTs) and
      hypermethylation in normal cells. PRESENTATION OF THE HYPOTHESIS: The innate
      tendency of DNA sequences present at fragile sites to form non-B DNA structures
      results in de novo methylation of DNA at these sites that is held in check in
      normal cells by the action of ATP-dependent and actin-dependent helicases coupled
      with the action of TET dioxygenases. This constitutes a previously unrecognized
      epigenetic repair cycle in which spontaneously forming non-B DNA structures
      formed at fragile sites are methylated by DNMTs as they are removed by the action
      of ATP-dependent and actin-dependent helicases, with the resulting nascent
      methylation rendered non-transmissible by TET dioxygenases. TESTING THE
      HYPOTHESIS: A strong prediction of the hypothesis is that knockdown of ATP
      dependent and actin-dependent helicases will result in enhanced bisulfite
      sensitivity and hypermethylation at non-B structures in multiple fragile sites
      coupled with global hypomethylation. IMPLICATIONS OF THE HYPOTHESIS: A key
      implication of the hypothesis is that helicases, like the lymphoid-specific
      helicase and alpha thalassemia/mental retardation syndrome X-linked helicase,
      passively promote accurate maintenance of DNA methylation by preventing the
      sequestration of DNMTs at sites of unrepaired non-B DNA structure. When helicase
      action is blocked due to mutation or downregulation of the respective genes,
      DNMTs stall at unrepaired non-B structures in fragile sites after methylating
      them and are unable to methylate other sites in the genome, resulting in
      hypermethylation at non-B DNA-forming sites, along with hypomethylation
      elsewhere.

PMID- 24079336
TI  - Diagnosing latent copper deficiency in intact barley leaves (Hordeum vulgare, L.)
      using near infrared spectroscopy.
AB  - Chemometric analysis of near-infrared (NIR) spectra recorded directly on fresh
      leaves of barley plants (Hordeum vulgare, L.) enabled the separation of control
      and Cu deficient samples before any visual deficiency symptoms developed. This
      demonstrates that the molecular structure of leaves is modified during latent Cu
      deficiency. Lignin biosynthesis is a primary target of Cu deficiency, but lignin
      concentrations were unaltered when separation was first possible, indicating that
      alteration of lignin composition, not concentration, is among the earliest
      effects of Cu deficiency in plants. Validation of chemometric models using an
      independent test set found that 92% of samples were correctly classified as
      control or Cu deficient, respectively. Models were undisturbed by including
      spectra from plants deficient in P, Mg, B, or Mn, establishing their specificity
      for Cu deficiency. This study is the first to demonstrate that NIR has the
      potential to successfully diagnose the deficiency of an essential trace element
      in plants. 

PMID- 24079337
TI  - Boryl-mediated reversible H2 activation at cobalt: catalytic hydrogenation,
      dehydrogenation, and transfer hydrogenation.
AB  - We describe the synthesis of a cobalt(I)-N2 complex (2) supported by a meridional
      bis-phosphino-boryl (PBP) ligand. Complex 2 undergoes a clean reaction with 2
      equiv of dihydrogen to afford a dihydridoboratocobalt dihydride (3). The ability
      of boron to switch between a boryl and a dihydridoborate conformation makes
      possible the reversible conversion of 2 and 3. Complex 3 reacts with HMe2N-BH3 to
      give a hydridoborane cobalt tetrahydridoborate complex. We explore this boryl
      cobalt system in the context of catalytic olefin hydrogenation as well as amine
      borane dehydrogenation/transfer hydrogenation. 

PMID- 24079338
TI  - Formulation, evaluation and 3(2) full factorial design-based optimization of
      ondansetron hydrochloride incorporated taste masked microspheres.
AB  - CONTEXT: Masking the bitter taste of Ondansetron hydrochloride (ONS) may improve
      palatability, acceptance and compliance of ONS products. OBJECTIVE: ONS-loaded,
      taste-masked microspheres were prepared with a polycationic pH-sensitive polymer
      and 3(2) full factorial design (FFD) was applied to optimize microsphere batches.
      MATERIALS AND METHODS: Solvent evaporation, in acetone--methanol/liquid paraffin
      system, was used to prepare taste-masked ONS microspheres. The effect of varying
      drug/polymer (D/P) ratios on microspheres characteristics were studied by 3(2)
      FFD. Desirability function was used to search the optimum formulation.
      Microspheres were evaluated by FTIR, XRD and DSC to examine interaction and
      effect of microencapsulation process. In vitro taste assessment approach based on
      bitterness threshold and drug release was used to assess bitterness scores.
      RESULTS: Prepared ONS microspheres were spherical and surface was wrinkled. ONS
      was molecularly dispersed in microspheres without any incompatibility with EE100.
      In hydrochloric acid buffer pH 1.2, ONS released completely from microsphere in
      just 10 min. Contrary to this, ONS release at initial 5 min from taste-masked
      microspheres was less than the bitterness threshold. CONCLUSION: Full factorial
      design and in vitro taste assessment approach, coupled together, was successfully
      applied to develop and optimize batches of ONS incorporated taste-masked
      microspheres.

PMID- 24079335
TI  - Acute treatment with relaxin protects the kidney against ischaemia/reperfusion
      injury.
AB  - Although recent preclinical and clinical studies have demonstrated that
      recombinant human relaxin (rhRLX) may have important therapeutic potential in
      acute heart failure and chronic kidney diseases, the effects of acute rhRLX
      administration against renal ischaemia/reperfusion (I/R) injury have never been
      investigated. Using a rat model of 1-hr bilateral renal artery occlusion followed
      by 6-hr reperfusion, we investigated the effects of rhRLX (5 MUg/Kg i.v.) given
      both at the beginning and after 3 hrs of reperfusion. Acute rhRLX administration
      attenuated the functional renal injury (increase in serum urea and creatinine),
      glomerular dysfunction (decrease in creatinine clearance) and tubular dysfunction
      (increase in urinary excretion of N-acetyl-beta-glucosaminidase) evoked by renal
      I/R. These beneficial effects were accompanied by a significant reduction in
      local lipid peroxidation, free radical-induced DNA damage and increase in the
      expression/activity of the endogenous antioxidant enzymes Mn- and CuZn-superoxide
      dismutases (SOD). Furthermore, rhRLX administration attenuated the increase in
      leucocyte activation, as suggested by inhibition of myeloperoxidase activity,
      intercellular-adhesion-molecule-1 expression, interleukin (IL)-1beta, IL-18 and
      tumour necrosis factor-alpha production as well as increase in IL-10 production.
      Interestingly, the reduced oxidative stress status and neutrophil activation here
      reported were associated with rhRLX-induced activation of endothelial nitric
      oxide synthase and up-regulation of inducible nitric oxide synthase, possibly
      secondary to activation of Akt and the extracellular signal-regulated protein
      kinase (ERK) 1/2, respectively. Thus, we report herein that rhRLX protects the
      kidney against I/R injury by a mechanism that involves changes in nitric oxide
      signalling pathway. 

PMID- 24079339
TI  - Dissipative particle dynamics studies of doxorubicin-loaded micelles assembled
      from four-arm star triblock polymers 4AS-PCL-b-PDEAEMA-b-PPEGMA and their pH
      release mechanism.
AB  - Dissipative particle dynamics (DPD) simulation was applied to investigate the
      microstructures of the micelles self-assembled from pH-sensitive four-arm star
      triblock poly(epsilon-caprolactone)-b-poly(2-(diethylamino)ethyl methacrylate)-b
      poly(poly(ethylene glycol) methyl ether methacrylate) (4AS-PCL-b-PDEAEMA-b
      PPEGMA). In the optimized system, the micelles have a core-mesosphere-shell three
      layer structure. The drug-loading process and its distribution at different
      formulations in the micelles were studied. The results show that DOX molecules
      distributed in the core and the interface between the core and the mesosphere,
      suggesting the potential encapsulation capacity of DOX molecules. More drugs were
      loaded in the micelles with the increase in DOX, and the size of micelles became
      larger. However, some openings start to generate on the PEG shell when the DOX
      reaches a certain concentration. By changing the pH values of the system,
      different morphologies of the micelles were acquired after the pH-sensitive
      blocks PDEAEMA were protonated, the mechanism of which was also analyzed through
      correlating functions. The results indicated that the sudden increase in
      solubility parameter of the pH-sensitive blocks and the swelling of the micelles
      were the key factors on the change of morphologies. Furthermore, with the
      decrease in pH value, the number and size of the cracks on the surface of the
      micelles were larger, which may have a direct effect on the drug release. In
      conclusion, 4AS-PCL-b-PDEAEMA-b-PPEGMA has great promising applications in
      delivering hydrophobic anticancer drugs for improved cancer therapy. 

PMID- 24079340
TI  - An efficient framework for estimation of muscle fiber orientation using
      ultrasonography.
AB  - BACKGROUND: Muscle fiber orientation (MFO) is an important parameter related to
      musculoskeletal functions. The traditional manual method for MFO estimation in
      sonograms was labor-intensive. The automatic methods proposed in recent years
      also involved voting procedures which were computationally expensive. METHODS: In
      this paper, we proposed a new framework to efficiently estimate MFO in sonograms.
      We firstly employed Multi-scale Vessel Enhancement Filtering (MVEF) to enhance
      fascicles in the sonograms and then the enhanced images were binarized. Finally,
      line-shaped patterns in the binary map were detected one by one, according to
      their shape properties. Specifically speaking, for the long-and-thinner regions,
      the orientation of the targeted muscle fibre was directly computed, without
      voting procedures, as the orientation of the ellipse that had the same normalized
      second central moments as the region. For other cases, the Hough voting procedure
      might be employed for orientation estimation. The performance of the algorithm
      was evaluated using four various group of sonograms, which are a dataset used in
      previous reports, 33 sonograms of gastrocnemius from 11 young healthy subjects,
      one sonogram sequence including 200 frames from a subject and 256 frames from an
      aged subject with cerebral infarction respectively. RESULTS: It was demonstrated
      in the experiments that measurements of the proposed method agreed well with
      those of the manual method and achieved much more efficiency than the previous Re
      voting Hough Transform (RVHT) algorithm. CONCLUSIONS: Results of the experiments
      suggested that, without compromising the accuracy, in the proposed framework the
      previous orientation estimation algorithm was accelerated by reduction of its
      dependence on voting procedures.

PMID- 24079342
TI  - Synthesis and crystal structure of the solid solution Co3(SeO3)3-x(PO3OH)x(H2O)
      involving crystallographic split positions of Se4+ and P5+.
AB  - Three new cobalt selenite hydroxo-phosphates laying in the solid solution
      Co3(SeO3)3-x(PO3OH)x(H2O), with x = 0.8, x = 1.0, and x = 1.2 are reported.
      Single crystals were obtained by hydrothermal synthesis and the crystal structure
      was determined by single crystal X-ray diffraction. The structure can be
      described as a 3D framework having selenite and hydroxo-phosphate groups
      protruding into channels in the crystal structure. Se(4+) and P(5+) share a split
      position in the structure so that either SeO3 groups having a stereochemically
      active lone pair or tetrahedrally coordinated PO3OH groups are present. The OH
      group is thus only present when the split position is occupied by P(5+). The
      crystal water is coordinated to a cobalt atom and TG and IR measurements show
      that the water and hydroxyl groups leave the structure at unusually high
      temperatures (>450  degrees C). Magnetic susceptibility measurements show
      antiferromagnetic coupling below 16 K and a magnetic moment of 4.02(3) MUB per Co
      atom was observed. 

PMID- 24079341
TI  - Exploring human breast milk composition by NMR-based metabolomics.
AB  - Breast milk is a complex fluid evolutionarily adapted to satisfy the nutritional
      requirements of growing infants. In addition, milk biochemical and immunological
      components protect newborns against infective agents in the new environment.
      Human milk oligosaccharides, the third most abundant component of breast milk,
      are believed to modulate the microbiota composition, thus influencing a wide
      range of physiological processes of the infant. Human milk also contains a number
      of other bioactive compounds, the functional role of which has not yet been
      clearly elucidated. In this scenario, NMR-based metabolic profiling can provide a
      rapid characterisation of breast milk composition, thus allowing a better
      understanding of its nutritional properties. 

PMID- 24079343
TI  - Deficiency for the ER-stress transducer OASIS causes severe recessive
      osteogenesis imperfecta in humans.
AB  - Osteogenesis imperfecta (OI) is a clinically and genetically heterogeneous
      brittle bone disorder. Whereas dominant OI is mostly due to heterozygous
      mutations in either COL1A1 or COL1A2, encoding type I procollagen, recessive OI
      is caused by biallelic mutations in genes encoding proteins involved in type I
      procollagen processing or chaperoning. Hitherto, some OI cases remain molecularly
      unexplained. We detected a homozygous genomic deletion of CREB3L1 in a family
      with severe OI. CREB3L1 encodes OASIS, an endoplasmic reticulum-stress transducer
      that regulates type I procollagen expression during murine bone formation. This
      is the first report linking CREB3L1 to human recessive OI, thereby expanding the
      OI gene spectrum. 

PMID- 24079344
TI  - An uncommon cause of acutely altered mental status in a renal transplant
      recipient.
AB  - INTRODUCTION: Neurological complications are quite frequent in patients after
      solid organ transplantation presenting with focal or generalized neurologic
      symptoms as well as altered mental status. Posterior reversible encephalopathy
      syndrome is a rare cliniconeuroradiological entity characterized by headache,
      altered mental status, cortical blindness, seizures, and other focal neurological
      signs and a diagnostic magnetic resonance imaging. CASE REPORT: We present a case
      of a 57-year-old woman with one episode of seizures and sudden onset of altered
      mental status (time and person perception) accompanied with headache at the
      thirtieth postoperative day after renal transplantation. CONCLUSION: Posterior
      reversible encephalopathy syndrome, although an uncommon post-renal
      transplantation complication, should be considered in these patients, as several
      factors surrounding the setting of transplantation have been implicated in its
      development. Thus, physicians should be aware of this condition in order to
      establish the diagnosis and offer appropriate treatment.

PMID- 24079345
TI  - Concordance between administrative health data and medical records for diabetes
      status in coronary heart disease patients: a retrospective linked data study.
AB  - BACKGROUND: Administrative data are a valuable source of estimates of diabetes
      prevalence for groups such as coronary heart disease (CHD) patients. The primary
      aim of this study was to measure concordance between medical records and linked
      administrative health data for recording diabetes in CHD patients, and to assess
      temporal differences in concordance. Secondary aims were to determine the optimal
      lookback period for identifying diabetes in this patient group, whether
      concordance differed for Indigenous people, and to identify predictors of false
      positives and negatives in administrative data. METHODS: A population
      representative sample of 3943 CHD patients hospitalized in Western Australia in
      1998 and 2002-04 were selected, and designated according to the International
      Classification of Diseases (ICD) version in use at the time (ICD-9 and ICD-10
      respectively). Crude prevalence and concordance were compared for the two
      samples. Concordance measures were estimated from administrative data comparing
      diabetes status recorded on the selected CHD admission ('index admission') and on
      any hospitalization in the previous 1, 2, 5, 10 or 15 years, against hospital
      medical records. Potential modifiers of agreement were determined using chi
      square tests and multivariable logistic regression models. RESULTS:
      Identification of diabetes on the index CHD admission was underestimated more in
      the ICD-10 than ICD-9 sample (sensitivity 81.5% versus 91.1%, underestimation
      15.1% versus 4.4% respectively). Sensitivity increased to 89.6% in the ICD-10
      period using at least 10 years of hospitalization history. Sensitivity was higher
      and specificity lower in Indigenous patients, and followed a similar pattern of
      improving concordance with increasing lookback period. Characteristics associated
      with false negatives for diabetes on the index CHD hospital admission were
      elective admission, in-hospital death, principal diagnosis, and in the ICD-10
      period only, fewer recorded comorbidities. CONCLUSIONS: The accuracy of
      identifying diabetes status in CHD patients is improved in linked administrative
      health data by using at least 10 years of hospitalization history. Use of this
      method would reduce bias when measuring temporal trends in diabetes prevalence in
      this patient group. Concordance measures are as reliable in Indigenous as non
      Indigenous patients.

PMID- 24079346
TI  - DNA detection using plasmonic enhanced near-infrared photoluminescence of gallium
      arsenide.
AB  - Efficient near-infrared detection of specific DNA with single nucleotide
      polymorphism selectivity is important for diagnostics and biomedical research.
      Herein, we report the use of gallium arsenide (GaAs) as a sensing platform for
      probing DNA immobilization and targeting DNA hybridization, resulting in ~8-fold
      enhanced GaAs photoluminescence (PL) at ~875 nm. The new signal amplification
      strategy, further coupled with the plasmonic effect of Au nanoparticles, is
      capable of detecting DNA molecules with a detection limit of 0.8 pM and
      selectivity against single base mismatches. Such an ultrasensitive near-infrared
      sensor can find a wide range of biochemical and biomedical applications. 

PMID- 24079347
TI  - Suitability of liposomal carriers for systemic delivery of risedronate using the
      pulmonary route.
AB  - OBJECTIVE: This study aims at testing the hypothesis that reversed phase
      evaporation liposomes (REVs) are suitable for systemic delivery of an anti
      osteporotic drug (risedronate sodium (RS)) via pulmonary nebulization. MATERIALS
      AND METHODS: RS REVs were prepared using phospholipids and cholesterol with or
      without stearylamine, and were characterized for morphology, entrapment
      efficiency (EE%), in vitro release, particle size and aerosolization behavior
      from an actively vibrating mesh nebulizer. RS accumulation in rat bones following
      intra-tracheal administration of the selected formulation was assessed using a
      radiolabelling-based technique, and histological examination of rat lung tissue
      was performed to assess its safety. RESULTS: The EE% of RS REVs ranged from 8.8%
      to 58.96% depending on cholesterol molar ratio, phospholipid type and presence of
      stearylamine. RS REVs' particle size ranged from 2.15 to 3.61 um and were
      spherical and moderately polydisperse. Nebulization of the selected formulation
      showed an aerosol output of 85%, a fine particle fraction of 70.75% and a
      predicted alveolar deposition of 30.39%. The amount of radiolabelled RS deposited
      in rat bones after pulmonary administration was 20%, while being considerably
      safe on lung tissues. CONCLUSION: Cationic REVs is a promising carrier for
      systemic delivery of RS for treatment of bone resorptive diseases.

PMID- 24079348
TI  - Critical role of the degree of substitution in the interaction of biocompatible
      cholic acid-modified dextrans with phosphatidylcholine liposomes.
AB  - The interaction between biocompatible cholic acid-modified dextrans with
      different pendent cholic acid groups' content and phosphatidylcholine liposomes
      was studied by a variety of techniques including isothermal titration calorimetry
      (ITC), differential scanning calorimetry (DSC), turbidity measurements,
      microscopy imaging (transmission electron microscopy (TEM), and cryo-scanning
      electron microscopy (cryo-SEM)). The variation of the interaction enthalpy with
      polymer concentration, as obtained by ITC, highlighted the formation of different
      aggregates. Complete phase modification, from vesicles covered with a few polymer
      chains to vesicle disintegration, was observed by turbidity measurements. DSC
      showed the effect of polymer addition to the liposome gel to liquid-crystalline
      phase transition, and microscopy images gave information about the size and
      morphology of the aggregates. The composition, structure, and morphology of
      polymer/liposome aggregates were found to be strongly influenced by the cholic
      acid content in the polymer (degree of substitution, DS). Along with a rather
      monotonous change in the polymer/liposome system's properties with increasing DS,
      a discontinuity in behavior could also be observed at DS = 4 mol %. For DS <= 4
      mol %, the polymer/liposome interaction takes place mainly between individual
      components, and liposome disintegration occurs in a narrow concentration range,
      whereas for DS > 4 mol % extended physical networks are formed, which last over a
      wide concentration range. A mechanism of interaction, as a function of DS, is
      proposed and discussed in detail. 

PMID- 24079349
TI  - Thermometry during MR-guided focused ultrasound in a preclinical model based on
      Thiel embalmed tissue.
AB  - BACKGROUND: The purpose of this work was to determine the accuracy of Proton
      Resonance Frequency (PRF) thermometry during MR-guided Focused Ultrasound
      (MRgFUS) ablation on explanted Thiel embalmed human and animal liver, fresh
      animal liver, and compared to gel phantom. MATERIAL AND METHODS: PRF thermometry
      during MRgFUS was conducted using a 1.5T MRI system. The phantom and the organs
      were sonicated with the following energies: 300J, 600J, 1000J and 1400J. The
      temperature increase which was measured using PRF thermometry during sonication
      was compared to actual temperature rise in the same conditions measured by fibre
      optic thermocouple. RESULTS: Sonication of fresh animal liver showed temperature
      differences varying between 0.27 degrees C and 0.40 degrees C, whereas the
      phantom results showed temperature differences from 0.23 degrees C to 0.40
      degrees C. For the Thiel embalmed organs, the temperature difference varied from
      1.17  degrees C to 3.13 degrees C for the ovine liver, and from 1.3 degrees C to
      3.10 degrees C for the human liver. CONCLUSION: The temperature differences
      measured in the fresh liver were small and similar to those found for the gel
      phantom. However, the temperature differences calculated for the Thiel embalmed
      organs were higher compared to the fresh organ. This indicates that the PRF-based
      temperature calibration of the Focused Ultrasound machine for Thiel embalmed
      tissue is necessary.

PMID- 24079350
TI  - Intra-arterial infusion of thrombin: animal experiments.
AB  - PURPOSE: Thrombin inhibits cadherin on vascular endothelial cells, rapidly and
      reversibly increasing endothelial permeability. The purpose of this study was to
      evaluate the feasibility of trans-arterial infusion with thrombin. MATERIAL AND
      METHODS: Ten rabbits with right thigh tumor were randomly divided into two
      groups: A thrombin group and a control group. In the thrombin group, a suspension
      of thrombin (300 IU), cisplatin (3 mg), lipiodol (0.3 ml) and iopamidol (0.3 ml)
      was infused into the right femoral artery. In the control group, a suspension of
      cisplatin, lipiodol and iopamidol was infused. Platinum concentrations in plasma
      were measured five and ten minutes after administration. Platinum concentrations
      were also measured in tumor specimens excised 30 minutes after infusion. RESULTS:
      At both five and ten minutes after infusion, platinum concentrations in plasma
      were significantly lower for the thrombin group than for the control group.
      Platinum concentration in tumor tissue was significantly higher for the thrombin
      group than for the control group. CONCLUSION: The present results suggest that
      transarterial infusion with thrombin may offer a number of pharmacological
      advantages.

PMID- 24079352
TI  - Assessment of an alternative postdeployment reintegration strategy with soldiers
      returning from Iraq.
AB  - The present study examined behavioral health outcomes, risk behaviors,
      aggression, alcohol misuse, marital satisfaction, and attitudes toward
      reintegration associated with an alternative, front-loaded reintegration strategy
      compared with a more standardized reintegration process in soldiers returning
      from combat deployments. The type of reintegration strategy used did not predict
      differences in posttraumatic stress disorder (PTSD) symptoms, alcohol misuse,
      aggression, and marital satisfaction, although slightly higher reports of risk
      behaviors were found in the unit using the standard reintegration approach even
      after controlling for demographic covariates and combat exposure. These findings
      may help guide leadership when making decisions regarding reintegration
      approaches in the future.

PMID- 24079353
TI  - The "specter" of cancer: exploring secondary trauma for health professionals
      providing cancer support and counseling.
AB  - Health professionals are vulnerable to occupational stress and tend to report
      high levels of secondary trauma and burnout; this is especially so for those
      working in "high-death" contexts such as cancer support and palliative care. In
      this study, 38 health professionals (psychologists, social workers, pastoral
      carers/chaplains, nurses, group facilitators, and a medical practitioner) who
      provide grief support and counseling in cancer and palliative care each
      participated in a semistructured interview. Qualitatively, a grounded theory
      analysis revealed four themes: (a) the role of health professionals in supporting
      people who are experiencing grief and loss issues in the context of cancer, (b)
      ways of working with patients with cancer and their families, (c) the unique
      qualities of cancer-related loss and grief experiences, and (d) the emotional
      demands of the work and associated self-care. The provision of psychological
      services in the context of cancer is colored by the specter of cancer, an unseen
      yet real phenomenon that contributes to secondary trauma and burnout. The
      participants' reported secondary trauma has serious repercussions for their well
      being and may compromise the care they provide. The findings have implications
      for the retention and well-being of personnel who provide psychosocial care in
      cancer and the quality and delivery of services for people with cancer and their
      families.

PMID- 24079351
TI  - HIV and hepatitis C virus test uptake at methadone clinics in Southern China:
      opportunities for expanding detection of bloodborne infections.
AB  - BACKGROUND: HIV and hepatitis C (HCV) co-infection is highly common among Chinese
      injection drug users but it is difficult to reach IDUs at traditional VCT
      (Voluntary HIV counseling treatment) clinics. A new national model integrating
      HIV/HCV testing with methadone maintenance treatment was started in 2006. The
      purpose of this study was to investigate HIV and HCV test uptake and associated
      factors at methadone clinics in Guangdong Province, China. METHODS: A cross
      sectional design using routine surveillance data and laboratory testing
      confirmation was applied to determine rates of HIV and HCV test uptake. Multi
      level modeling was used to examine individual-level and clinic-level correlates
      of increased test uptake. RESULTS: 45 out of 49 methadone clinics in Guangdong
      Province agreed to participate in the study. Among all 13,270 individuals, 10,046
      (75.7%) had HIV test uptake and 10,404 (78.4%) had HCV uptake. At the individual
      level, methadone clients 30 years or older were more likely to have HIV and HCV
      test uptake (p <0.001 for both). At the clinic level, methadone clinics with
      greater health care personnel were more likely to have HIV (p = 0.01) and HCV (p
      = 0.044) test uptake. HIV test uptake significantly correlated with HCV test
      uptake (correlation coefficient = 0.64). CONCLUSION: Methadone clinics provide an
      opportunity for routine integrated HIV and HCV screening among drug users in
      China. Increased test uptake in young drug users and increased health care
      personnel at clinics may further improve screening.

PMID- 24079354
TI  - Homeless veterans in supported housing: exploring the impact of criminal history.
AB  - This article described the criminal histories of a multisite sample of homeless
      veterans enrolled in the Housing and Urban Development-Veterans Affairs
      Supportive Housing (HUD-VASH) program, presented a method of categorizing them,
      and compared outcomes among veterans with different criminal histories. A
      national dataset on a total of 1,160 participants over a 1-year period was
      analyzed. Cluster analyses were conducted on the criminal histories of
      participants and groups of participants were compared on program entry
      characteristics and outcomes. Before entry into the HUD-VASH program, 79% of
      participants had been charged with at least one criminal charge. The most common
      criminal charges were disorderly conduct, vagrancy, and public intoxication. At
      program entry, participants with more extensive criminal histories showed poorer
      status in employment, housing, substance abuse, and quality of life compared with
      participants with minor or no criminal histories. However, once enrolled in
      supported housing, there were no group differences in outcomes and all groups
      showed substantial improvements in housing. These findings suggest that most
      homeless veterans have had involvement in the criminal justice system, albeit
      mostly to a small extent. Supported housing programs, like HUD-VASH, that serve
      homeless veterans regardless of their criminal history should be supported.

PMID- 24079355
TI  - Successfully breaking a 20-year cycle of hospitalizations with recovery-oriented
      cognitive therapy for schizophrenia.
AB  - Individuals with severe and persistent schizophrenia can present challenges
      (e.g., difficulties sustaining motivation and conducting information processing
      tasks) to the implementation of recovery-oriented care. We present a successful
      application of recovery-oriented cognitive therapy (CT-R), a fusion of the spirit
      and principles of the recovery movement with the evidence base and know-how of
      cognitive therapy, that helped an individual with schizophrenia move along her
      recovery path by overcoming specific obstacles, including a 20-year cycle of
      hospitalizations (five per year), daily phone calls to local authorities,
      threatening and berating "voices," the belief that she would be killed at any
      moment, and social isolation. Building on strengths, treatment included
      collaboratively identifying meaningful personal goals that were broken down into
      successfully accomplishable tasks (e.g., making coffee) that disconfirmed
      negative beliefs and replaced the phone calling. At the end of treatment and at a
      6-month follow-up, the phone calls had ceased, psychosocial functioning and
      neurocognitive performance had increased, and avolition and positive symptoms had
      decreased. She was not hospitalized once in 24 months. Results suggest that
      individuals with schizophrenia have untapped potential for recovery that can be
      mobilized through individualized, goal-focused psychosocial interventions.

PMID- 24079357
TI  - Evaluating the state of quality-improvement science through evidence synthesis:
      insights from the closing the quality gap series.
AB  - CONTEXT: The Closing the Quality Gap series from the Agency for Healthcare
      Research and Quality summarizes evidence for eight high-priority health care
      topics: outcomes used in disability research, bundled payment programs, public
      reporting initiatives, health care disparities, palliative care, the patient
      centered medical home, prevention of health care-associated infections, and
      medication adherence. OBJECTIVE: To distill evidence from this series and provide
      insight into the "state of the science" of quality improvement (QI). METHODS: We
      provided common guidance for topic development and qualitatively synthesized
      evidence from the series topic reports to identify cross-topic themes,
      challenges, and evidence gaps as related to QI practice and science. RESULTS:
      Among topics that examined effectiveness of QI interventions, we found
      improvement in some outcomes but not others. Implementation context and potential
      harms from QI activities were not widely evaluated or reported, although market
      factors appeared important for incentive-based QI strategies. Patient-focused and
      systems-focused strategies were generally more effective than clinician-focused
      strategies, although the latter approach improved clinician adherence to
      infection prevention strategies. Audit and feedback appeared better for targeting
      professionals and organizations, but not patients. Topic reviewers observed
      heterogeneity in outcomes used for QI evaluations, weaknesses in study design,
      and incomplete reporting. CONCLUSIONS: Synthesizing evidence across topics
      provided insight into the state of the QI field for practitioners and
      researchers. To facilitate future evidence synthesis, consensus is needed around
      a smaller set of outcomes for use in QI evaluations and a framework and lexicon
      to describe QI interventions more broadly, in alignment with needs of decision
      makers responsible for improving quality.

PMID- 24079358
TI  - Characterization of a bisphenol A specific yeast bioreporter utilizing the
      bisphenol A-targeted receptor.
AB  - The first Saccharomyces cerevisiae yeast bioreporter for analysis of a single
      endocrine disrupting compound, bisphenol A (BPA), was developed. The bioreporter
      contains mutated human estrogen receptor alpha (hERalpha), called bisphenol A
      targeted receptor (BPA-R). The BPA-R bioreporter was characterized with mixtures
      of estrogenic chemicals and tested with spiked influent wastewater samples. The
      detection limit for BPA was 4.2-fold lower (0.107 MUM, i.e., 24 MUg L(-1)), while
      that of the native hormone 17beta-estradiol (E2) (1 MUM, i.e., 272 MUg L(-1)) was
      166,000-fold higher compared to the wild type hERalpha bioreporter. The BPA-R
      bioreporter responded only to BPA in a chemical cocktail and spiked concentrated
      wastewater samples with high concentrations of other estrogenic chemicals. As a
      conclusion, wastewater and other environmental water samples can be concentrated
      and specifically analyzed for BPA without risk of the mixture effect caused by
      other estrogenic chemicals. The BPA-R bioreporter is a robust and cost-efficient
      choice for high-throughput monitoring of BPA and its bioavailability in complex
      samples. 

PMID- 24079359
TI  - Multifunctional TiO2-C/MnO2 core-double-shell nanowire arrays as high-performance
      3D electrodes for lithium ion batteries.
AB  - The unique TiO2-C/MnO2 core-double-shell nanowires are synthesized for the first
      time using as anode materials for lithium ion batteries (LIBs). They combine both
      advantages from TiO2 such as excellent cycle stability and MnO2 with high
      capacity (1230 mA h g(-1)). The additional C interlayer intends to improve the
      electrical conductivity. The self-supported nanowire arrays grown directly on
      current-collecting substrates greatly simplify the fabrication processing of
      electrodes without applying binder and conductive additives. Each nanowire is
      anchored to the current collector, leading to fast charge transfer. The unique
      one-dimensional core-double-shell nanowires exhibit enhanced electrochemical
      performance with a higher discharge/charge capacity, superior rate capability,
      and longer cycling lifetime. 

PMID- 24079360
TI  - Substrate-directable electron transfer reactions. Dramatic rate enhancement in
      the chemoselective reduction of cyclic esters using SmI2-H2O: mechanism, scope,
      and synthetic utility.
AB  - Substrate-directable reactions play a pivotal role in organic synthesis, but are
      uncommon in reactions proceeding via radical mechanisms. Herein, we provide
      experimental evidence showing dramatic rate acceleration in the Sm(II)-mediated
      reduction of cyclic esters that is enabled by transient chelation between a
      directing group and the lanthanide center. This process allows unprecedented
      chemoselectivity in the reduction of cyclic esters using SmI2-H2O and for the
      first time proceeds with a broad substrate scope. Initial studies on the origin
      of selectivity and synthetic application to form carbon-carbon bonds are also
      disclosed. 

PMID- 24079361
TI  - Development and evaluation of oral osmotic pump of butorphanol tartrate.
AB  - Butorphanol is potent analgesic useful in pain management. However, because of
      high first-pass metabolism butorphanol is not available in market as oral dosage
      form. Drugs that undergo extensive first-pass metabolism can be delivered orally
      if protected in the stomach, and proximal small intestine. An oral controlled
      porosity osmotic pump (CPOP) was designed to deliver butorphanol tartrate that
      can maintain therapeutic blood concentration up to 24 h. The target release
      profile for extended release formulation was calculated by Wagner Nelson de
      convolution using published immediate release blood concentration data for oral
      route. Composition of the core and coating were optimized using USFDA approved
      ingredients by evaluation of the drug release. Drug release from the developed
      system was inversely proportional to the weight gain and directly related to the
      level of pore former. Scanning electron microscopy (SEM) confirmed the formation
      of pores in the coating membrane on contact with water which lead to drug to
      release. Kinetic models were applied to drug release data to establish the drug
      release mechanism. The developed osmotic system effectively delivers selected
      drug at a predetermined rate for extended period.

PMID- 24079362
TI  - Oral vancomycin desensitisation to treat Clostridium difficile infection in a
      vancomycin allergic patient.
AB  - The prevalence of Clostridium difficile infection (CDI) is increasing worldwide.
      Oral vancomycin is an effective and frequently used treatment. However, patients
      with CDI who are allergic to intravenous vancomycin cannot receive oral
      vancomycin due to the risk of anaphylaxis if given the oral form.We present a
      case where oral vancomycin desensitisation was used to successfully treat a
      vancomycin allergic patient with recurrent CDI. 

PMID- 24079363
TI  - The MRN protein complex genes: MRE11 and RAD50 and susceptibility to head and
      neck cancers.
AB  - BACKGROUND: The members of MRE11/RAD50/NBN (MRN) protein complex participates in
      DNA double-strand break repair and DNA-damage checkpoint activation. We have
      previously shown that the p.I171V NBN gene mutation may contribute to the
      development of laryngeal cancer. This study tested the hypothesis that variants
      of the MRE11 and RAD50 genes, previously described as cancer risk factors,
      predispose to increased susceptibility to head and neck cancer. FINDINGS: In this
      study we analyzed the RAD50 and MRE11 genes in 358 patients: 175 with a single
      laryngeal cancer (LC), 115 with multiple primary tumors but one malignancy
      (primary or second) localized in the larynx (MPT-LC), 68 patients with multiple
      primary tumors localized in the head or neck (MPT) and 506 controls. No carriers
      of previously reported mutation in the MRE11 or RAD50 gene (particularly the
      pathogenic c.687delT) were detected in the present study. We identified the
      p.V127I variant (2/175 LC, 2/506 controls; OR=2.91; 95% CI 0.41-20.85) and
      p.V315L variant (2/115 MPT-LC, 1/506 controls; OR=8.96; 95% CI 0.81-99.68) of the
      RAD50 gene. CONCLUSIONS: Our data indicated that previously described common
      genetic variations in the MRE11 and RAD50 genes do not contribute to an increased
      risk of laryngeal cancer and second primary tumors localized in the head and
      neck. Prospective studies with larger groups of patients may reveal the possible
      impact of these genes in tumor occurrence.

PMID- 24079364
TI  - [Prevention of cardiovascular diseases needs prevention for arteriosclerosis
      development and its risk factors].

PMID- 24079365
TI  - Statins and percutaneous coronary intervention: a complementary synergy.
AB  - The inclusion of statins and stents in coronary disease management during the
      1980s has marked a dramatic change in the natural history of the disease.
      Separately, each of these therapies have progressed rapidly and have achieved a
      prime position in the current armamentarium. The simultaneous use of statins in
      patients undergoing percutaneous coronary revascularization procedures with stent
      implantation has shown a significant beneficial synergistic effect by reducing
      ischemia and necrosis, and improving coronary blood flow in patients with stable
      coronary disease, as well as in acute coronary syndromes. The use of high dose
      statins in conjunction with coronary angioplasty with stent implantation has
      shown great efficacy and safety in patients with severe coronary disease. 

PMID- 24079366
TI  - Psychosocial difficulties in alcohol dependence: a systematic review of activity
      limitations and participation restrictions.
AB  - PURPOSE: There has been a lack of comprehensive reviews targeting specific
      aspects of functioning and the difficulties faced by persons with alcohol
      dependence. The aim of the present review was to systematically compile the
      existing literature on activity limitations and participation restrictions as
      defined in the International Classification of Functioning, Disability and Health
      (ICF) in the context of alcohol dependence. METHODS: A database search (MEDLINE
      and PsychINFO) was performed for studies published in English (2005-2012),
      examining the activity limitations and participation restrictions in alcohol
      dependence. Using a standardised protocol, information about the studies'
      characteristics and data on activity limitations and participation restrictions,
      their evolution, onset, determinants and associations with other variables were
      extracted from the studies under review. RESULTS: A total of 211 difficulties in
      activities and participation in persons with alcohol dependence were extracted
      from 125 papers. The spectrum of studies was wide, and their overall quality was
      good. A common reason for the exclusion of studies was an inconclusive definition
      of alcohol dependence. Issues with interpersonal interactions, economic and
      professional life, dealing with aggression and legal problems were the most
      frequently reported difficulties. Problems with high-risk behaviours and in
      seeking appropriate treatment were also common. The most frequent determinants of
      the onset and evolution of the identified difficulties were factors pertaining to
      the course of alcohol dependence. These difficulties were rarely the studies'
      focus; therefore, the data on their underlying causes and courses were limited.
      CONCLUSIONS: The results confirm that alcohol dependence profoundly affects the
      family and social network of the afflicted person. The treatment of alcohol
      dependence can contribute to the alleviation of these associated difficulties.
      The ICF offers a new perspective on evaluating the wide range of difficulties
      encountered in the context of alcohol dependence. IMPLICATIONS FOR
      REHABILITATION: Alcohol dependence profoundly affects the family and social
      network of the afflicted person. The most frequent difficulties in activities and
      participation have to do with interpersonal interactions, economic and work life,
      dealing with aggression and legal problems. Problems with high-risk behaviours
      and in seeking appropriate treatment are also common. Treatment targeted at
      reduction or cessation of alcohol use is effective in reducing these psychosocial
      difficulties. The ICF offers a structure for systematic evaluation of the wide
      range of difficulties encountered in alcohol dependence.

PMID- 24079367
TI  - New glycosidase substrates for droplet-based microfluidic screening.
AB  - Droplet-based microfluidics is a powerful technique allowing ultra-high
      throughput screening of large libraries of enzymes or microorganisms for the
      selection of the most efficient variants. Most applications in droplet
      microfluidic screening systems use fluorogenic substrates to measure enzymatic
      activities with fluorescence readout. It is important, however, that there is
      little or no fluorophore exchange between droplets, a condition not met with most
      commonly employed substrates. Here we report the synthesis of fluorogenic
      substrates for glycosidases based on a sulfonated 7-hydroxycoumarin scaffold. We
      found that the presence of the sulfonate group effectively prevents leakage of
      the coumarin from droplets, no exchange of the sulfonated coumarins being
      detected over 24 h at 30  degrees C. The fluorescence properties of these
      substrates were characterized over a wide pH range, and their specificity was
      studied on a panel of relevant glycosidases (cellulases and xylanases) in
      microtiter plates. Finally, the beta-d-cellobioside-6,8-difluoro-7
      hydroxycoumarin-4-methanesulfonate substrate was used to assay cellobiohydrolase
      activity on model bacterial strains (Escherichia coli and Bacillus subtilis) in a
      droplet-based microfluidic format. These new substrates can be used to assay
      glycosidase activities in a wide pH range (4-11) and with incubation times of up
      to 24 h in droplet-based microfluidic systems. 

PMID- 24079368
TI  - Solvent-responsive wettability of self-assembled monolayers of dithiooctanoic
      acid derivatives bearing N,N-disubstituted amide groups.
AB  - We have designed and synthesized two dithiooctanoic acid derivatives bearing N,N
      disubstituted amide groups and used them to fabricate self-assembled monolayers
      (SAMs) on gold surface. These films showed a reversible changes in wettability,
      one of which was indicated by surface contact angle switching between 40 degrees 
      and 59 degrees  upon alternating treatment with ethanol and cyclohexane. NMR
      experimental results of a model molecule suggest that the solvent-responsive
      wettability of the SAMs could be related with the changes in the relative
      populations of two stereoisomers of amide. The solvent responsivity of SAMs
      fabricated from other two amides was also studied, and the results confirmed that
      N,N-disubstitution was essential for an amide-containing SAM to have stimuli
      responsivity. Thus, introduction of a functional group exhibiting controlled
      isomerization of conformation could be an effective strategy for designing new
      stimuli-responsive materials. 

PMID- 24079369
TI  - Signatures of nanoconfinement on the linear and nonlinear vibrational
      spectroscopy of a model hydrogen-bonded complex dissolved in a polar solvent.
AB  - The one-dimensional IR (1D-IR) absorption and IR pump-probe spectra of a hydrogen
      stretch in a model hydrogen-bonded complex dissolved in a polar solvent confined
      in spherical hydrophobic cavities of different sizes were simulated using ground
      state mixed quantum-classical dynamics. Due to a thorough analysis of key
      properties of the complex and solvent from equilibrium trajectory data, we were
      able to gain insight into the microscopic details underlying the spectra. Both
      the 1D-IR and IR pump-probe spectra manifested the effects of confinement on the
      relative stabilities of the covalent and ionic forms of the complex through
      pronounced changes in their peak intensities and numbers. However, in contrast to
      the 1D-IR spectra, the time-resolved pump-probe spectra were found to be uniquely
      sensitive to the changes in the molecular dynamics as the cavity size is varied.
      In particular, it was found that the variations in the time evolutions of the
      peak intensities in the pump-probe spectra reflect the differences in the
      solvation dynamics associated with the various forms of the complex in different
      locations within the cavities. The ability to detect these differences
      underscores the advantage of using pump-probe spectroscopy for studying
      nanoconfined systems. 

PMID- 24079370
TI  - Weak ferromagnetic transition with a dielectric anomaly in hexagonal
      Lu0.5Sc0.5FeO3.
AB  - Lu1-xScxFeO3 (0 <= x <= 1) was synthesized by a conventional solid-state
      reaction. The hexagonal phase appeared at 0.4 <= x <= 0.6, between the perovskite
      phase (0 <= x <= 0.3) and the bixbyite phase (0.7 <= x <= 1). Structural,
      magnetic, and dielectric properties of hexagonal Lu0.5Sc0.5FeO3 were
      investigated. Synchrotron X-ray diffraction measurements revealed that the
      crystal structure of Lu0.5Sc0.5FeO3 is isomorphic to hexagonal ferroelectrics
      RMnO3 (R = rare earth ion) with a polar space group of P63cm. A weak
      ferromagnetic transition with a dielectric anomaly occurred at a much higher
      temperature (162 K) than those in hexagonal RMnO3. Although remanent
      magnetization was observed below the transition temperature, it decreased to
      almost zero at 10 K. These results indicate a strong antiferromagnetic
      interaction between ground-state Fe(3+) ions on the triangular lattice. 

PMID- 24079371
TI  - Comparative study of antioxidant properties and total phenolic content of the
      extracts of Humulus lupulus L. and quantification of bioactive components by LC
      MS/MS and GC-MS.
AB  - In this research, antioxidant activities of various extracts obtained from
      Humulus lupulus L. were compared by DPPH, ABTS, FRAP, and CUPRAC assays. The
      amount of total phenolic components determined by the Folin-Ciocalteu reagent was
      found to be highest for 25% aqueous ethanol (9079 +/- 187.83 mg Ferulic acid
      equivalent/100 g extract) and methanol-1 (directly) (8343 +/- 158.39 mg Ferulic
      acid equivalent/100 g extract) extracts. The n-hexane extract of H. lupulus
      exhibited the greatest with DPPH (14.95 +/- 0.03 MUg Trolox equivalent/g sample).
      The highest phenolic content in the ethanolic extract could be the major
      contributor to its highest CUPRAC activity (3.15 +/- 0.44 mmol Trolox
      equivalent/g sample). Methanol-2 (n-hexane, acetone, and methanol) and methanol-3
      (n-hexane, dichloromethane, ethylacetate, and methanol) extracts, respectively,
      exhibited the most potent ABTS (7.35 +/- 0.03 mM Trolox equivalent) and FRAP
      (1.56 +/- 0.35 mmol Fe(2+)/g sample) activities. Some of the components from the
      crude extracts were determined by LC-MS/MS and GC-MS analyses. Comparative
      screening of antioxidant activities of H. lupulus extracts and quantification of
      some major components by LC-MS/MS, qualitatively analysis of the reported ones
      which were optimal under negative ion SIM mode and coinjection, are going to be
      valuable for food and health applications. 

PMID- 24079372
TI  - Burkitt Lymphoma: beyond discoveries.
AB  - First described in 1958 in Uganda, Burkitt lymphoma (BL) attracted interest
      worldwide following reports of its uneven geographic distribution and rapidly
      fatal clinical course. Both suggested infectious etiology and curability. Seminal
      discoveries followed in quick succession. Viral etiology - due to Epstein-Barr
      virus (EBV) - was confirmed. Chromosomal translocations, involving cellular MYC,
      a protooncogene, were discovered, shown to be a hallmark of BL, and central to
      the genetic basis of cancer. Cure of BL using combination chemotherapy was
      demonstrated. Unfortunately, civil disturbance in Africa disrupted BL research
      and blunted its impact on education and oncology care in Africa. Important
      questions went unanswered. The risk of BL due to malaria or EBV was not
      quantified. Efforts to answer whether BL could be prevented - by preventing
      malaria or early EBV infection - were abandoned. The mechanism of malaria in BL
      is unknown. In Africa, BL remains mostly fatal and diagnosis is still made
      clinically. Unprecedented advances in molecular, genomics and proteomic
      technologies, promising to unlock mysteries of cancers, have re-awakened interest
      in BL. With return of stability to Africa, the unanswered questions about BL are
      re-attracting global interest. This interest now includes exploiting the
      knowledge gained about genetics, proteomics, and bioinformatics to enable the
      development of targeted less toxic treatment for BL; and simpler methods to
      diagnose BL with high accuracy and sensitivity. The articles in the Burkitt
      Lymphoma (BL): Beyond Discoveries in Infectious Agents and Cancer highlight BL as
      priority. Authors explore etiology, pathology, pathogenesis of BL, and whether
      knowledge gained in the studies of BL can catalyze sustainable cancer services in
      one of the world's poorest served regions. 

PMID- 24079374
TI  - Rearrangement reactions of lithiated oxiranes.
AB  - The first computational study of the rearrangement reactions of oxiranes
      initiated by lithium dialkylamides is presented. Aside from the well-known
      carbenoid insertion pathways, both beta-elimination and alpha-lithiation have
      been suggested as the exclusive mechanism by which oxiranes react in the presence
      of organolithium bases. The products of the former are allyl alcohols (and, in
      some cases, dienes) and are ketones in the case of the latter. The computational
      studies reported in this work indicate that both mechanisms could be
      simultaneously operational. In particular, our work shows that the allyl alcohols
      from beta-elimination are unlikely to undergo 1,3-hydrogen transfer to the vinyl
      alcohols and thus to the ketones, suggesting that ketones are formed through the
      opening of the oxirane ring after alpha-substitution. Elimination of LiOH from
      the lithiated allyl alcohol is found to result in the diene product. Low
      activation barriers for beta-elimination are offered as the explanation for the
      few special cases where the allyl alcohol is the dominant or exclusive product.
      These findings are consistent with the product distributions observed in several
      experiments. 

PMID- 24079375
TI  - Spontaneously hypertensive rats: possible animal model of sleep-related movement
      disorders.
AB  - Clinical experience suggests that restless legs syndrome (RLS), periodic leg
      movement (PLM), and attention-deficit hyperactivity disorder (ADHD) may co-occur
      in both children and adults. The purpose of the present study was to provide an
      electrocorticography and electromyography evaluation of the spontaneously
      hypertensive rat (SHR) to investigate the potential of this rat strain as an
      animal model of RLS-PLM. Initial work focused on evaluating sleep patterns and
      limb movements during sleep in SHR, having normotensive Wistar rats (NWR) as
      control, followed by comparison of two treatments (pharmacological-dopaminergic
      agonist treatment and nonpharmacological-chronic physical exercise), known to be
      clinically beneficial for sleep-related movement disorders. The captured data
      strengthen the association between SHR and RLS-PLM, revealing a significant
      reduction on sleep efficiency and slow wave sleep and an increase on wakefulness
      and limb movements for the SHR group during the dark period, as compared to the
      NWR group, effects that have characteristics that are strikingly consistent with
      RLS-PLM. The pharmacological and nonpharmacological manipulations validated these
      results. The present findings suggest that the SHR may be a useful putative
      animal model to study sleep-related movement disorders mechanisms.

PMID- 24079373
TI  - The International Study of Childhood Obesity, Lifestyle and the Environment
      (ISCOLE): design and methods.
AB  - BACKGROUND: The primary aim of the International Study of Childhood Obesity,
      Lifestyle and the Environment (ISCOLE) was to determine the relationships between
      lifestyle behaviours and obesity in a multi-national study of children, and to
      investigate the influence of higher-order characteristics such as behavioural
      settings, and the physical, social and policy environments, on the observed
      relationships within and between countries. METHODS/DESIGN: The targeted sample
      included 6000 10-year old children from 12 countries in five major geographic
      regions of the world (Europe, Africa, the Americas, South-East Asia, and the
      Western Pacific). The protocol included procedures to collect data at the
      individual level (lifestyle, diet and physical activity questionnaires,
      accelerometry), family and neighborhood level (parental questionnaires), and the
      school environment (school administrator questionnaire and school audit tool). A
      standard study protocol was developed for implementation in all regions of the
      world. A rigorous system of training and certification of study personnel was
      developed and implemented, including web-based training modules and regional in
      person training meetings. DISCUSSION: The results of this study will provide a
      robust examination of the correlates of adiposity and obesity in children,
      focusing on both sides of the energy balance equation. The results will also
      provide important new information that will inform the development of lifestyle,
      environmental, and policy interventions to address and prevent childhood obesity
      that may be culturally adapted for implementation around the world. ISCOLE
      represents a multi-national collaboration among all world regions, and represents
      a global effort to increase research understanding, capacity and infrastructure
      in childhood obesity.

PMID- 24079376
TI  - Validated RP-HPLC and HPTLC methods for determination of anti-inflammatory bis
      indole alkaloid in Desmodium gangeticum.
AB  - Here, two simple and accurate methods, namely high-performance liquid
      chromatography and high-performance thin-layer chromatography for the detection
      of gangenoid, an anti-inflammatory alkaloid, in a well-known Indian medicinal
      plant Desmodium gangeticum, are described. The proposed methods were successfully
      used for the estimation of gangenoid in D. gangeticum root. 

PMID- 24079377
TI  - Large ongoing measles outbreak in a religious community in the Netherlands since
      May 2013.
AB  - Despite vaccination coverage over 95%, a measles outbreak started in May 2013 in
      the Netherlands. As of 28 August, there were 1,226 reported cases, including 82
      hospitalisations. It is anticipated that the outbreak will continue. Most cases
      were orthodox Protestants (n=1,087/1,186; 91.7%) and unvaccinated (n=1,174/1,217;
      96.5%). A unique outbreak control intervention was implemented: a personal
      invitation for measles-mumps-rubella (MMR) vaccination was sent for all children
      aged 6-14 months living in municipalities with MMR vaccination coverage below
      90%.

PMID- 24079379
TI  - Population susceptibility to North American and Eurasian swine influenza viruses
      in England, at three time points between 2004 and 2011.
AB  - Age-stratified sera collected in 2004, 2008 and 2010 in England were evaluated
      for antibody to swine influenza A(H3N2) and A(H1N1) viruses from the United
      States or Europe as a measure of population susceptibility to the emergence of
      novel viruses. Children under 11 years of age had little or no measurable
      antibody to recent swine H3N2 viruses despite their high levels of antibody to
      recent H3N2 seasonal human strains. Adolescents and young adults (born 1968-1999)
      had higher antibody levels to swine H3N2 viruses. Antibody levels to swine H3N2
      influenza show little correlation with exposure to recent seasonal H3N2
      (A/Perth/16/2009) strains, but with antibody to older H3N2 strains represented by
      A/Wuhan/359/1995. Children had the highest seropositivity to influenza
      A(H1N1)pdm09 virus, and young adults had the lowest antibody levels to
      A/Perth/16/2009. No age group showed substantial antibody levels to
      A/Aragon/RR3218/2008, a European swine H1N1 virus belonging to the Eurasian
      lineage. After vaccination with contemporary trivalent vaccine we observed
      evidence of boosted reactivity to swine H3N2 viruses in children and adults,
      while only a limited boosting effect on antibody levels to A/Aragon/RR3218/2008
      was observed in both groups. Overall, our results suggest that different
      vaccination strategies may be necessary according to age if swine viruses emerge
      as a significant pandemic threat.

PMID- 24079378
TI  - Seroepidemiology for MERS coronavirus using microneutralisation and
      pseudoparticle virus neutralisation assays reveal a high prevalence of antibody
      in dromedary camels in Egypt, June 2013.
AB  - We describe a novel spike pseudoparticle neutralisation assay (ppNT) for
      seroepidemiological studies on Middle East respiratory syndrome coronavirus
      (MERSCoV) and apply this assay together with conventional microneutralisation
      (MN) tests to investigate 1,343 human and 625 animal sera. The sera were
      collected in Egypt as a region adjacent to areas where MERS has been described,
      and in Hong Kong, China as a control region. Sera from dromedary camels had a
      high prevalence of antibody reactive to MERS-CoV by MERS NT (93.6%) and MERS ppNT
      (98.2%) assay. The antibody titres ranged up to 1,280 and higher in MN assays and
      10,240 and higher in ppNT assays. No other investigated species had any antibody
      reactivity to MERS-CoV. While seropositivity does not exclude the possibility of
      infection with a closely related virus, our data highlight the need to attempt
      detection of MERSCoV or related coronaviruses in dromedary camels. The data show
      excellent correlation between the conventional MN assay and the novel ppNT assay.
      The newly developed ppNT assay does not require Biosafety Level 3 containment and
      is thus a relatively high-throughput assay, well suited for large-scale
      seroepidemiology studies which are needed to better understand the ecology and
      epidemiology of MERS-CoV.

PMID- 24079380
TI  - Reduction of the nosocomial meticillin-resistant Staphylococcus aureus incidence
      density by a region-wide search and follow-strategy in forty German hospitals of
      the EUREGIO, 2009 to 2011.
AB  - Meticillin-resistant Staphylococcus aureus (MRSA) disseminates between hospitals
      serving one patient catchment area. Successful prevention and control requires
      concerted efforts and regional surveillance. Forty hospitals located in the
      German EUREGIO have established a network for combating MRSA. In 2007 they agreed
      upon a synchronised strategy for screening of risk patients and a standard for
      transmissionbased precautions (search and follow). The same year, the hospitals
      started synchronised MRSA prevention and annually reporting MRSA-data to the
      public health authorities. The median rate of screening cultures per 100 patients
      admitted increased from 4.38 in 2007 to 34.4 in 2011 (p<0.0001). Between 2007 and
      2011, the overall incidence density of MRSA (0.87 MRSA cases/1,000 patient days
      vs 1.54; p<0.0001) increased significantly. In contrast, both the incidence
      density of nosocomial MRSA cases (0.13 nosocomial MRSA cases/1,000 patient days
      in 2009 vs 0.08 in 2011; p=0.0084) and the MRSA-days-associated nosocomial MRSA
      rate (5.51 nosocomial MRSA cases/1,000 MRSA days in 2009 vs 3.80 in 2011;
      p=0.0437) decreased significantly after the second year of the project. We
      documented adherence to the regional screening strategy resulting in improved
      detection of MRSA carriers at admission. Subsequently, after two years the
      nosocomial MRSA-incidence density was reduced. Regional surveillance data,
      annually provided as benchmarking to the regional hospitals and public health
      authorities, indicated successful prevention.

PMID- 24079384
TI  - An investigation of the effects of antiretroviral central nervous system
      penetration effectiveness on procedural learning in HIV+ drug users.
AB  - Treatment with combination antiretroviral therapy (cART) regimens with a high
      capacity to penetrate the blood-brain barrier has been associated with lower
      levels of human immunodeficiency virus (HIV) in the central nervous system (CNS).
      This study examined neurocognitive performance among a sample of 118 HIV+
      substance-dependent individuals (SDIs) and 310 HIV- SDIs. HIV+ participants were
      prescribed cART regimens with varying capacity to penetrate the CNS as indexed by
      the revised CNS Penetration Effectiveness (CPE) scale. Participants completed the
      Rotary Pursuit Task (RPT) and the Weather Prediction Task (WPT)-two measures of
      procedural learning (PL) with known sensitivity to HIV infection-and a control
      task of sustained attention. HIV+ SDIs prescribed cART with relatively high CNS
      penetrance performed significantly more poorly on both tasks than HIV- controls.
      Task performance of HIV+ SDIs prescribed cART with relatively low CNS penetrance
      did not differ significantly from either HIV- controls or the HIV+/high CPE
      group, although a trend toward lower RPT performance than that of HIV-
      participants was observed. Between-group differences were not seen on a control
      task of motor impulsivity (Immediate Memory Task), indicating that the observed
      deficits among HIV+/high CPE SDIs may have some specificity. 

PMID- 24079385
TI  - Live intracellular super-resolution imaging using site-specific stains.
AB  - Point localization super-resolution imaging (SR) requires dyes that can cycle
      between fluorescent and dark states, in order for their molecular positions to be
      localized and create a reconstructed image. Dyes should also densely decorate
      biological features of interest to fully reveal structures being imaged. We
      tested site-specific dyes in several live-cell compatible imaging media and
      evaluated their performance in situ. We identify a number of new dyes and imaging
      medium-dye combinations for live staining, that densely highlight intracellular
      structures with excellent photophysical performance for SR. 

PMID- 24079386
TI  - Quantitative proteomics.

PMID- 24079387
TI  - Attentional retraining can reduce chocolate consumption.
AB  - There is emerging evidence that attentional biases are related to the consumption
      of substances such as alcohol and tobacco, and that attentional bias modification
      can reduce unwanted consumption of these substances. We present evidence for the
      first time to our knowledge that the same logical argument applies in the food
      and eating domain. We conducted two experiments that used a modified dot probe
      paradigm to train undergraduate women to direct their attention toward ("attend")
      or away from ("avoid") food cues (i.e., pictures of chocolate). In Experiment 1,
      attentional bias for chocolate cues increased in the "attend" group, and
      decreased in the "avoid" group. Experiment 2 showed that these training effects
      generalized to novel, previously unseen chocolate pictures. Importantly,
      attentional retraining affected chocolate consumption and craving. In both
      experiments, participants in the "avoid" group ate less chocolate in a so-called
      taste test than did those in the "attend" group. In addition, in Experiment 2,
      but not in Experiment 1, the "attend" group reported stronger chocolate cravings
      following training, whereas the "avoid" group reported less intense cravings. The
      results support predictions of cognitive-motivational models of craving and
      consumption that attentional biases play a causal role in consumption behavior.
      Furthermore, they present a promising avenue for tackling unwanted food cravings
      and (over)eating.

PMID- 24079388
TI  - In vitro effects of nicotine on human spermatozoa.
AB  - Washed human spermatozoa from 12 normozoospermic donors were treated with
      different concentrations of nicotine 0.1, 1.0, 5.0 and 10.0 mm and were compared
      to spermatozoa suspended in nutrient medium only (control). Computer-aided sperm
      analysis was used to assess sperm kinematic properties after 30, 60, 120 and 180
      min of incubation. Viability was assessed by means of a dye exclusion staining
      technique (eosin/nigrosin), while acrosome-reacted cells were identified under a
      fluorescent microscope using fluorescein isothiocyanate-Pisum sativum agglutinin
      as a probe. Nicotine significantly reduced total motility, progressive motility,
      curvilinear velocity, amplitude of lateral head displacement, beat cross
      frequency, viability and caused spontaneous acrosome reaction at concentrations
      of >=5.0 mm after 2 and 3 h of exposure. Nicotine concentrations of 0.1 and 1.0
      mm had no significant effect (P < 0.05) on spermatozoa except that 1.0 mm
      significantly decreased (P < 0.05) sperm progressive motility at 2 and 3 h of
      incubation as well as viability after 3 h of incubation. This study concludes
      that the occurrence of high levels of nicotine in the body and seminal fluid
      might adversely affect fertilisation capacity of human spermatozoa through a
      mechanism that involves decreased motility, viability and premature induction of
      the acrosome reaction.

PMID- 24079389
TI  - Regioselective allene hydrosilylation catalyzed by N-heterocyclic carbene
      complexes of nickel and palladium.
AB  - Regioselective methods for allene hydrosilylation have been developed, with
      regioselectivity being governed primarily by the choice of metal. Alkenylsilanes
      are produced via nickel catalysis with larger N-heterocyclic carbene (NHC)
      ligands, and allylsilanes are produced via palladium catalysis with smaller NHC
      ligands. These complementary methods allow either regioisomeric product to be
      obtained with exceptional regiocontrol. 

PMID- 24079390
TI  - Amorphous Si thin film based photocathodes with high photovoltage for efficient
      hydrogen production.
AB  - An amorphous Si thin film with TiO2 encapsulation layer is demonstrated as a
      highly promising and stable photocathode for solar hydrogen production. With
      platinum as prototypical cocatalyst, a photocurrent onset potential of 0.93 V vs
      RHE and saturation photocurrent of 11.6 mA/cm(2) are measured. Importantly, the a
      Si photocathodes exhibit impressive photocurrent of ~6.1 mA/cm(2) at a large
      positive bias of 0.8 V vs RHE, which is the highest for all reported
      photocathodes at such positive potential. Ni-Mo alloy is demonstrated as an
      alternative low-cost catalyst with onset potential and saturation current similar
      to those obtained with platinum. This low-cost photocathode with high
      photovoltage and current is a highly promising photocathode for solar hydrogen
      production.

PMID- 24079391
TI  - Obstacles to the prevention of overweight and obesity in the context of child
      health care in Sweden.
AB  - BACKGROUND: Overweight and obesity in younger children could better be brought in
      focus through a deeper understanding of how Child Health Care nurses (CHC-nurses)
      perceive their work with the problems of overweight at the CHC Centers. The aim
      of this study was to elucidate the CHC-nurses conceptions of their preventive
      work with childhood overweight and obesity in Child Health Care. METHOD: A
      qualitative study, based on open-ended interviews, involving 18 CHC-nurses
      strategically selected from 17 CHC Centres in the southern part of Sweden using a
      phenomenographic approach. RESULTS: Two categories of description emerged from
      the data: (i) Internal obstacles to the CHC- nurses' work with overweight in
      children and (ii) External obstacles to the management of overweight in children.
      The CHC-nurses conceived their work with overweight in Child Health Care to be
      complicated and constrained by several obstacles depending on the nurses'
      personal priorities, knowledge, responsibility and the absence of resources and
      cooperation, as well as the lack of uniform guidelines for preventing and
      managing childhood overweight and further a deficient management organisation.
      CONCLUSION: Nurses' attention to monitoring overweight in children, and their
      initiative for prevention, is based on their conceptions of the obstacles that
      hinder them in their efforts. An increased awareness of the CHC-nurses
      conceptions of the priorities, their sense of responsibility and prevention
      practices is warranted. If measures in this direction are not taken there is a
      growing risk that overweight children will pass through the CHC without any
      formal recognition of their situation. There is an indication that the present
      level of the CHC-nurses' preventive work with childhood overweight has room for
      improvement in several areas. It is suggested that the specialist education of
      these health care professionals should be supplemented and that organisation of
      the management of childhood overweight should be also revised at the primary
      health care level.

PMID- 24079393
TI  - Evolution of eye development in the darkness of caves: adaptation, drift, or
      both?
AB  - Animals inhabiting the darkness of caves are generally blind and de-pigmented,
      regardless of the phylum they belong to. Survival in this environment is an
      enormous challenge, the most obvious being to find food and mates without the
      help of vision, and the loss of eyes in cave animals is often accompanied by an
      enhancement of other sensory apparatuses. Here we review the recent literature
      describing developmental biology and molecular evolution studies in order to
      discuss the evolutionary mechanisms underlying adaptation to life in the dark. We
      conclude that both genetic drift (neutral hypothesis) and direct and indirect
      selection (selective hypothesis) occurred together during the loss of eyes in
      cave animals. We also identify some future directions of research to better
      understand adaptation to total darkness, for which integrative analyses relying
      on evo-devo approaches associated with thorough ecological and population genomic
      studies should shed some light. 

PMID- 24079394
TI  - Management of climatic heat stress risk in construction: a review of practices,
      methodologies, and future research.
AB  - Climatic heat stress leads to accidents on construction sites brought about by a
      range of human factors emanating from heat induced illness, and fatigue leading
      to impaired capability, physical and mental. It is an occupational characteristic
      of construction work in many climates and the authors take the approach of re
      engineering the whole safety management system rather than focusing on
      incremental improvement, which is current management practice in the construction
      industry. From a scientific viewpoint, climatic heat stress is determined by six
      key factors: (1) air temperature, (2) humidity, (3) radiant heat, and (4) wind
      speed indicating the environment, (5) metabolic heat generated by physical
      activities, and (6) "clothing effect" that moderates the heat exchange between
      the body and the environment. By making use of existing heat stress indices and
      heat stress management processes, heat stress risk on construction sites can be
      managed in three ways: (1) control of environmental heat stress exposure through
      use of an action-triggering threshold system, (2) control of continuous work time
      (CWT, referred by maximum allowable exposure duration) with mandatory work-rest
      regimens, and (3) enabling self-paced working through empowerment of employees.
      Existing heat stress practices and methodologies are critically reviewed and the
      authors propose a three-level methodology for an action-triggering, localized,
      simplified threshold system to facilitate effective decisions by frontline
      supervisors. The authors point out the need for "regional based" heat stress
      management practices that reflect unique climatic conditions, working practices
      and acclimatization propensity by local workers indifferent geographic regions.
      The authors set out the case for regional, rather than international, standards
      that account for this uniqueness and which are derived from site-based rather
      than laboratory-based research. 

PMID- 24079395
TI  - Copper-mediated cyanotrifluoromethylation of styrenes using the Togni reagent.
AB  - Styrenes with an electron-deficient double bond undergo cyanotrifluoromethylation
      with a trifluoromethylated hypervalent iodine reagent in the presence of CuCN.
      The reaction proceeds under mild conditions in the presence of bulky phosphines
      or B2pin2 additives. The process is highly regioselective and involves the
      consecutive formation of two C-C bonds in a single addition reaction. In the
      presence of a p-methoxy substituent in the styrene, oxytrifluoromethylation
      occurs instead of the cyanotrifluoromethylation. 

PMID- 24079396
TI  - Neurophysiological substrates of stroke patients with motor imagery-based Brain
      Computer Interface training.
AB  - We investigated the efficacy of motor imagery-based Brain Computer Interface (MI
      based BCI) training for eight stroke patients with severe upper extremity
      paralysis using longitudinal clinical assessments. The results were compared with
      those of a control group (n = 7) that only received FES (Functional Electrical
      Stimulation) treatment besides conventional therapies. During rehabilitation
      training, changes in the motor function of the upper extremity and in the
      neurophysiologic electroencephalographic (EEG) were observed for two groups.
      After 8 weeks of training, a significant improvement in the motor function of the
      upper extremity for the BCI group was confirmed (p < 0.05 for ARAT),
      simultaneously with the activation of bilateral cerebral hemispheres.
      Additionally, event-related desynchronization (ERD) of the affected sensorimotor
      cortexes (SMCs) was significantly enhanced when compared to the pretraining
      course, which was only observed in the BCI group (p < 0.05). Furthermore, the
      activation of affected SMC and parietal lobe were determined to contribute to
      motor function recovery (p < 0.05). In brief, our findings demonstrate that MI
      based BCI training can enhance the motor function of the upper extremity for
      stroke patients by inducing the optimal cerebral motor functional reorganization.

PMID- 24079397
TI  - GDFs promote tenogenic characteristics on human periodontal ligament-derived
      cells in culture at late passages.
AB  - Tendon/ligament injures are leading disabilities worldwide. The periodontal
      ligament (PDL) connects teeth to bone, and is comparable to a tendon/ligament-to
      bone insertion. PDL-derived cells (PDLCs) express both osteo/cementogenesis and
      teno/ligamentogenesis genes. However, an efficient method to induce a tenogenic
      differentiation of PDLCs has not been thoroughly examined. Therefore, this study
      tested if growth/differentiation factors (GDFs) enhanced tenogenic
      characteristics of human PDLCs, as a potential cell source for tendon/ligament
      engineering. Results demonstrated recombinant GDF-5/GDF-7 inhibited alkaline
      phosphatase (ALP) activity of PDLCs from passage 3 to 6, while GDF-5 enhanced ALP
      in dental pulp-derived cells and mesenchymal stem cells. GDF-5 (particularly at
      10 ng/ml concentration) induced high expression of both early (scleraxis) and
      mature (tenomodulin, aggrecan, collagen3) tenogenic genes in P4-6 PDLCs, while
      inhibiting expression of specific transcription-factors for osteogenic,
      chondrogenic and adipogenic differentiation. Exogenous GDFs might lead PDLCs
      being expanded in culture during several passages to highly useful cell source
      for tendon/ligament engineering.

PMID- 24079398
TI  - The test-negative design: validity, accuracy and precision of vaccine efficacy
      estimates compared to the gold standard of randomised placebo-controlled clinical
      trials.
AB  - The test-negative design (TND) is an efficient form of case-control study
      commonly applied to influenza vaccine effectiveness (VE) estimation. TND validity
      is predicated on the core assumption that the intervention (vaccine) has no
      effect on other non-targeted aetiologies resulting in similar illness/disease.
      Here we verify this core assumption and compare efficacy estimates derived by the
      TND versus classical per-protocol analysis of four datasets obtained from
      randomised placebo-controlled clinical trials (RCT) of the live attenuated
      influenza vaccine (LAIV) in children <=7 years-old and the elderly >=60 years
      old. We further assess generalisability of the TND approach in two other RCT
      datasets to evaluate monoclonal antibody in the prevention of respiratory
      syncytial virus (RSV) hospitalisation. Efficacy estimates and their confidence
      intervals were virtually identical for per-protocol RCT versus TND analyses of
      LAIV and also for RSV monoclonal antibody. Neither LAIV nor monoclonal antibodies
      affected the risk of disease aetiologies that were not specifically targeted by
      the respective interventions (e.g. other respiratory viruses). This study
      validates the core assumption of the TND approach for influenza vaccine efficacy
      estimation and confirms the accuracy and precision of its estimates compared to
      the gold standard of classic per-protocol RCT analysis of the same data sets. The
      TND approach is generalisable for other conditions such as RSV for which the core
      assumption is also met. However, when used in observational studies, the TND,
      like all designs, still requires assessment for bias and confounding that may
      exist in the absence of randomised participation and blinded follow-up.

PMID- 24079399
TI  - Laboratory-confirmed invasive meningococcal disease: effect of the Hajj
      vaccination policy, Saudi Arabia, 1995 to 2011.
AB  - Saudi Arabia (SA) experienced two large invasive meningococcal disease (IMD)
      outbreaks during the 2000 and 2001 Hajj pilgrimages. In 2002, polysaccharide
      quadrivalent ACWY vaccines became mandatory for Mecca and Medina
      pilgrims/residents older than two years. This study aimed to analyse IMD
      surveillance data among citizens, residents and pilgrims in SA from 1995 to 2011,
      focusing on changes before and after the new vaccination policy. For all
      laboratory-confirmed IMD cases in the national surveillance database from 1995 to
      2011, serogroup and age were retrieved. The cases' seasonal distribution as well
      as the case fatality ratios (CFR) were obtained. For Saudi citizens/residents and
      Hajj pilgrims, annual rates were calculated using mid-year population estimates.
      The Student's t-test was used to compare means between the pre-epidemic (1995
      1999) and post-epidemic (2002-2011) periods, excluding outbreak years. From 1995
      to 2011, laboratories notified 1,103 cases. Between the pre- and post-epidemic
      periods, mean annual IMD rates decreased from 0.20 (standard deviation (SD): 0.1)
      to 0.06 cases/100,000 (SD: 0.06; p=0.02), mean numbers of Hajj-related cases from
      13 (SD: 9.3) to 2 cases/year (SD: 2.3; p=0.02) and the mean age from 31 (SD: 1.3)
      to 18 years (SD: 1.4; p<0.01). The CFR in Saudi citizens (10.4) was lower than
      among foreign pilgrims (28.9) and decreased from 19.3% (SD: 1.8) in the pre
      epidemic to 11.4% (SD: 7.0; p=0.04) in the post-epidemic phase. The decrease of
      annual IMD rates, CFR and Hajj-related cases between the pre- and post- vaccine
      era suggests a possible positive effect of the mandatory ACWY vaccination for
      pilgrims/residents in Mecca and Medina. Regular surveillance with an annual data
      analysis is necessary to monitor trends and circulating serotypes and to
      implement appropriate public health measures to avoid new IMD epidemics during
      upcoming Hajj seasons.

PMID- 24079400
TI  - Investigating the link between the presence of enteroaggregative Escherichia coli
      and infectious intestinal disease in the United Kingdom, 1993 to 1996 and 2008 to
      2009.
AB  - There are an estimated 17 million human diarrhoea cases annually in the United
      Kingdom. In 2008 and 2009, enteroaggregative E. coli (EAEC) were identified in
      1.9% of stools. However, it remains unclear whether there is a causal link
      between presence of EAEC and disease. This study used bacterial load, the
      presence of co-infections and demographic data to assess if EAEC was
      independently associated with intestinal infectious disease. Quantitative real
      time PCR data (Ct values) generated directly from stool specimens for several
      pathogen targets were analysed to identify multiple pathogens, including EAEC, in
      the stools of cases and healthy controls. Sensitivity and specificity using Ct
      value (60% and 60%) was not useful for identifying cases or controls, but an
      independent association between disease and EAEC presence was demonstrated:
      multivariate logistic regression for EAEC presence (odds ratio: 2.41; 95%
      confidence interval: 1.78-3.26; p<0.001). The population-attributable fraction
      was 3.3%. The group of bacteria known as EAEC are associated with
      gastrointestinal disease in at least half of the cases with EAEC positive stools.
      We conclude that the current definition of EAEC, by plasmid gene detection,
      includes true pathogens as well as non-pathogenic variants.

PMID- 24079401
TI  - First joint meeting of three European tuberculosis networks.

PMID- 24079403
TI  - Subjective difficulty of movements with ongoing visual control.
AB  - Objective difficulty of a single-component visually controlled movement may be
      defined by Fitts's (1954) Index of Difficulty, which is a measure of difficulty
      in the sense that movement time is linearly related to the objective measure. For
      movements that have multiple components, it becomes difficult to determine an
      objective measure of task difficulty due to unknown interactions between
      components of the movement and interactions with other factors. Thus, it may be
      necessary to use indirect methods for allocating a measure of task difficulty.
      The purpose of the study was to determine whether participants could validly
      construct a subjective measure of the movement difficulty and whether this
      measure was related to the known objective measure of difficulty. Experiments
      showed that for single-component movements, there was a close relationship
      between measures of subjective and objective difficulty. With two-component
      visually controlled movements it was found that subjective difficulty could be
      related to objective difficulty, but not as simply as for single-component tasks.

PMID- 24079404
TI  - Quantitation of nanoparticle accumulation in flow using optimized microfluidic
      chambers.
AB  - BACKGROUND: The vascular cell adhesion molecule-1 (VCAM-1) targeting peptide
      sequence, VHPKQHR, is a promising moiety for targeting atherosclerosis through
      incorporation into nanoparticles such as dendrimers and liposomes. PURPOSE: We
      aim to develop VCAM-1-targeted nanoparticles that effectively accumulate on the
      endothelium under shear conditions and to develop robust microfluidic chambers
      able to house sufficient cells for flow cytometric measurements. METHODS:
      Carboxyfluorescein-labeled monomeric VHP-peptide, tetrameric VHP-dendrimers
      (bisbidentate or radial architecture, with or without N-terminal acetylation) and
      VHP-peptide liposomes were prepared. Human umbilical vein endothelial cells were
      treated with nanoparticles under 0 or 2.9 dyne/cm(2) shear, and particle binding
      was quantified. Flow chambers cured at various temperatures, with or without
      glass backings were fabricated, characterized for deformation and applied in
      experiments. RESULTS: Although liposomes accumulated with highest efficiency,
      dendrimers also demonstrated specific binding. N-terminal acetylation
      significantly reduced dendrimer binding, and despite shorter movement range,
      bisbidentate dendrimers outperformed radial dendrimers, suggesting multiple
      epitope presence within its estimated arm-span of 57 A. Under shear, while
      liposome binding increased 300%, dendrimer binding to cells decreased 65%.
      Through higher temperature curing and glass backing insertion,
      polydimethylsiloxane flow chambers maintaining rectangular cross-section with
      aspect-ratio as low as 1:111 were achieved. CONCLUSION: Optimized dendrimers and
      liposomal nanocarriers specifically accumulated onto cells within microfluidic
      chambers.

PMID- 24079405
TI  - A simple, fast, and sensitive assay for the detection of DNA, thrombin, and
      adenosine triphosphate based on Dual-Hairpin DNA structure.
AB  - In the present study, based on multifunctional Dual-Hairpin DNA structure, a
      simple, fast and high sensitive assay for the detection of DNA, thrombin and
      adenosine triphosphate (ATP) was demonstrated. DNA sequence labeled with
      methylene blue (MB), which was designed as single-stranded DNA (ssDNA) matching
      with target DNA, thrombin, or ATP aptamer, hybridized to the adjunct probe and
      formed the dual-hairpin structure on the electrode. With the hybridization of
      adjunct probe and the hairpin-like capture probe in the stem region, the dual
      hairpin was formed with outer and inner hairpins. By the conjugation of the
      target probe with the adjunct probe in the outer hairpin, the adjunct probe
      divorced from the dual-hairpin structure. The adjunct probe with signal molecules
      MB, attaching near or divorcing far from the electrode, produced electrochemical
      signal change and efficient electron transfer due to the fact that it was in
      proximity to the electrode. However, upon hybridization with the perfect match
      target, the redox label with the target probe was forced away from the modified
      electrode, thus resulting in the change of the Dual-Hairpin DNA conformation,
      which enables impedance of the efficient electron transfer of MB and,
      consequently, a detectable change of the electrochemical response. In addition,
      another highlight of this biosensor is its regenerability and stability owing to
      the merits of structure. Also, based on this Dual-Hairpin platform, the detection
      limits of DNA, thrombin, and ATP were 50 nM, 3 pM, and 30 nM, respectively.
      Moreover, this pattern also demonstrated excellent regenerability,
      reproducibility, and stability. Additionally, given to its ease-of-use,
      simplicity in design, easy operations, as well as regenerability and stability,
      the proposed approach may be applied as an excellent design prompter in the
      preparation of other molecular sensors. 

PMID- 24079406
TI  - Local modification of speed of sound in lithium alumino-silicate glass/ceramic
      material by pulsed laser irradiation and thermal processing.
AB  - Glass and glass/ceramics are now used in modern devices with increasing
      frequency. A list of the notable material properties commonly will not include a
      capability to guide ultrasonic waves. The photosensitive glass ceramics (PSGCs),
      an old invention with recent technological rebirth, may enable this capability.
      The speed of sound (SoS) has been measured at an ultrasonic frequency (75 MHz) in
      a commercially available PSGC material. The measurements are made using a pulse
      echo time-of-flight (TOF) technique as a function of UV laser exposure and
      thermal processing. The measured increase in the SoS correlates with the density
      of crystalline matter present, which can be metered by controlling the exposure
      dose. For the Li2SiO3 crystalline phase, the results show the shear (transverse)
      wave mode velocity can be increased by 4.8% relative to an unexposed area where
      no crystalline matter exists. The maximum change in velocity for the longitudinal
      (compressional) wave mode is only 2%. However, by altering the thermal processing
      protocols to grow the high temperature Li2Si2O5 crystalline phase, the measured
      change in the SoS increases to 11% and 9%, respectively. These results permit the
      volumetric patterning of delay lines by laser direct write techniques for
      generating complex profile ultrasonic wave patterns. Moreover, by patterned 3D
      shaping (i.e., photostructuring), ultrasound energy can be harnessed and utilized
      to advantage. 

PMID- 24079408
TI  - Value of a pilot study.

PMID- 24079407
TI  - Residue-dependent adsorption of model oligopeptides on gold.
AB  - The adsorption to gold surfaces in aqueous solutions has been systematically
      evaluated for a series of model oligopeptides. The series includes GG-X-GG "host
      guest" sequences, where the central X residue is one of 19 proteinogenic amino
      acids, and water-soluble X5 and X10 homo-oligopeptides. Irreversible adsorption
      on gold of GG-X-GG peptides, which lack significant secondary structure, was
      quantitatively analyzed by X-ray photoelectron spectroscopy (XPS). The broad
      range of the quasi-equilibrium surface densities measured by XPS corroborates the
      hypothesis that surface interactions of GG-X-GG peptides are dominated by their
      central X residues. The highest surface density was produced by GGCGG, followed
      by sequences with hydrophobic, charged, and polar central residues. Neither
      electrostatic nor hydrophobic interactions dominate the adsorption of GG-X-GG
      peptides: for charged and polar central residues, surface densities correlate
      with the size of the side chains but not with the sign of the charges, while for
      hydrophobic residues, the surface densities are uncorrelated with side-chain
      hydrophobicity. An intriguing result is the disparity in surface adsorption of
      structural isomers of Leu and Val, which exhibit a correlation between the
      position of the branched carbon in the side chain and the interaction of the
      peptide backbone with the surface. The surface density produced by the adsorption
      of GG-X-GG peptides overall was low; however, adsorption tended to increase as
      the number of X residues increased (GG-X-GG < X5 < X10), suggesting that
      cooperative binding is important for surface attachment of proteins that readily
      adsorb on inorganic surfaces. The Leu and Val isomer investigation and trends
      revealed by our analysis show how the methodology and results described here
      provide a fundamental reference for future experimental and computational studies
      and for rational design of peptides that exhibit predictable adsorption behaviors
      on a given surface. 

PMID- 24079409
TI  - Engaging RN-to-BSN students in Medical Reserve Corps training.

PMID- 24079410
TI  - Endotherapy versus surgery for early neoplasia in Barrett's esophagus: a meta
      analysis.
AB  - BACKGROUND: Esophagectomy is the conventional treatment for Barrett's esophagus
      with high-grade dysplasia and intramucosal cancer. Endotherapy is an alternative
      treatment. OBJECTIVE: To compare the efficacy and safety of these 2 treatments.
      DESIGN: PubMed, Web of Science, EMBASE, Cochrane Library and momentous meeting
      abstracts were searched. Studies comparing endotherapy with esophagectomy were
      included in the meta-analysis. Pooling was conducted in a random-effects model.
      SETTING: Tertiary-care facility. PATIENTS: Seven studies involving 870 patients
      were included. INTERVENTION: Endotherapy and esophagectomy. MAIN OUTCOME
      MEASUREMENTS: Neoplasia remission rate, neoplasia recurrence rate, overall
      survival rate, neoplasia-related death, and major adverse events. RESULTS: Meta
      analysis showed that there was no significant difference between endotherapy and
      esophagectomy in the neoplasia remission rate (relative risk [RR] 0.96; 95% CI,
      0.91-1.01); overall survival rate at 1 year (RR 0.99; 95% CI, 0.94-1.03), 3 years
      (RR 1.03; 95% CI, 0.96-1.10), and 5 years (RR 1.00; 95% CI, 0.93-1.06); and
      neoplasia-related mortality (risk difference [RD] 0; 95% CI, -0.02 to 0.01).
      Endotherapy was associated with a higher neoplasia recurrence rate (RR 9.50; 95%
      CI, 3.26-27.75) and fewer major adverse events (RR 0.38; 95% CI, 0.20-0.73).
      LIMITATIONS: Relatively small number of retrospective studies available,
      different types of endoscopic treatments were used. CONCLUSION: Endotherapy and
      esophagectomy show similar efficacy except in the neoplasia recurrence rate,
      which is higher after endotherapy. Prospective, randomized, controlled trials are
      needed to confirm these results.

PMID- 24079411
TI  - Cost-effectiveness of endoscopic surveillance of non-dysplastic Barrett's
      esophagus.
AB  - BACKGROUND: Endoscopic surveillance for non-dysplastic Barrett's esophagus (BE)
      is contentious and its cost effectiveness unclear. OBJECTIVE: To perform an
      economic analysis of endoscopic surveillance strategies. DESIGN: Cost-utility
      analysis by using a simulation Markov model to synthesize evidence from large
      epidemiologic studies and clinical data for surveillance, based on international
      guidelines, applied in a coordinator-managed surveillance program. SETTING:
      Tertiary care hospital, South Australia. PATIENTS: A total of 2040 patient-years
      of follow-up. INTERVENTION: (1) No surveillance, (2) 2-yearly endoscopic
      surveillance of patients with non-dysplastic BE and 6-monthly surveillance of
      patients with low-grade dysplasia, (3) a hypothetical strategy of biomarker
      modified surveillance. MAIN OUTCOME MEASUREMENTS: U.S. cost per quality-adjusted
      life year (QALY) ratios. RESULTS: Compared with no surveillance, surveillance
      produced an estimated incremental cost per QALY ratio of $60,858. This was
      reduced to $38,307 when surveillance practice was modified by a hypothetical
      biomarker-based strategy. Sensitivity analyses indicated that the likelihood that
      surveillance alone was cost-effective compared with no surveillance was 16.0% and
      60.6% if a hypothetical biomarker-based strategy was added to surveillance, at an
      acceptability threshold of $100,000 per QALY gained. LIMITATIONS: Treatment
      options for BE that overlap those for symptomatic GERD were omitted. CONCLUSION:
      By using best available estimates of the malignant potential of BE, endoscopic
      surveillance of patients with non-dysplastic BE is unlikely to be cost-effective
      for the majority of patients and depends heavily on progression rates between
      dysplasia grades. However, strategies that modify surveillance according to
      cancer risk might be cost-effective, provided that high-risk individuals can be
      identified and prioritized for surveillance.

PMID- 24079412
TI  - Sperm characteristics, antioxidant status and hormonal profile in rats treated
      with artemisinin.
AB  - The indiscriminate use, abuse and patients' noncompliance to normal prescription
      of artemisinin and its derivatives are a common practice during the treatment for
      drug-resistant malaria parasites in most developing countries. This study
      investigated the influence of artemisinin on the testicular and epididymal sperm
      antioxidant systems as well as on the plasma levels of hormones from the
      pituitary and thyroid components of the brain-pituitary-testicular axis. Oral
      exposure of rats to 0, 7 and 35 mg kg(-1) artemisinin for 7 days showed that the
      testicular antioxidant status at both therapeutic dose (7 mg kg(-1) ) and
      overdose (35 mg kg(-1) ), and the sperm antioxidant status at therapeutic dose of
      artemisinin remained unaffected compared with control. However, increased
      hydrogen peroxide and lipid peroxidation levels were accompanied by a concomitant
      decrease in glutathione peroxidase and glutathione-S-transferase activities as
      well as glutathione level in spermatozoon of rats administered with overdose of
      artemisinin. While plasma levels of all the hormones investigated remained
      unaffected, severe epididymal degeneration with concomitant decrease in sperm
      quantity and quality was observed in rats treated with overdose of artemisinin
      compared with control. Overall, induction of oxidative stress in the epididymis,
      but not in the testes, could cause reproductive deficits in individuals unduly
      undergoing artemisinin therapy.

PMID- 24079413
TI  - Inhibition of oxidized-phospholipid-induced vascular smooth muscle cell
      proliferation by resveratrol is associated with reducing Cx43 phosphorylation.
AB  - Abnormal proliferation of vascular smooth muscle cells (VSMCs) is an important
      factor during the progression of atherosclerosis. In this study, we investigated
      the effects of resveratrol on atherosclerosis-associated proliferation of VSMCs.
      We utilized an oxidized phospholipid, 1-palmitoyl-2-oxovaleroyl-sn-glycero-3
      phosphorylcholine (POVPC) to induce abnormal proliferation of VSMCs. Our results
      showed the treatments with resveratrol dose-dependently abolished POVPC-induced
      VSMC proliferation, as evidenced by the decreased [(3)H]thymidine incorporated
      into VSMCs and reduced percentage of 5-ethynyl-2'-deoxyuridine (EdU)-positive
      VSMCs. Cell cycle analysis demonstrated that resveratrol inhibited POVPC-induced
      increase in the S phase cell population and DNA synthesis. Our study further
      indicated that POVPC-induced VSMC proliferation was associated with a significant
      increase in the phosphorylation of Cx43, which was a consequence of activation of
      MAPK signaling. Interestingly, treatment with resveratrol abolished POVPC-induced
      phosphorylation of Cx43 as a result of inhibiting activation of Src, MEK, and
      ERK1/2. Our results provided a novel mechanism by which resveratrol may
      contribute to cardiovascular protection. 

PMID- 24079414
TI  - Control of life-or-death decisions by RIP1 kinase.
AB  - RIP1 kinase, a multifunctional protein that contains an N-terminal Ser/Thr kinase
      and a C-terminal death domain, has emerged as a key regulatory molecule involved
      in regulating both cell death and cell survival. When the proinflammatory
      cytokine TNFalpha stimulates its receptor, TNFR1, RIP1 regulates whether the cell
      lives by activating NF-kappaB or dies by apoptosis or necroptosis, two distinct
      pathways of programmed cell death that may be activated to eliminate unwanted
      cells. The kinase domain of RIP1 is involved in regulating necroptosis, and the
      death domain regulates RIP1 recruitment to the intracellular domain of TNFR1. The
      intermediate domain of RIP1 activates NF-kappaB and also interacts with RIP3
      kinase, a downstream mediator of RIP1 in the execution of necroptosis. This
      review focuses on the functional roles of RIP1 in regulating multiple cellular
      mechanisms, the dynamic regulation of RIP1, and the physiological and
      pathological roles of RIP1 kinase in human health and disease. 

PMID- 24079415
TI  - Direct reprogramming of fibroblasts into myocytes to reverse fibrosis.
AB  - Heart disease is a major cause of morbidity and mortality worldwide. The low
      regenerative capacity of adult human hearts has thus far limited the available
      therapeutic approaches for heart failure. Therefore, new therapies that can
      regenerate damaged myocardium and improve heart function are urgently needed.
      Although cell transplantation-based therapies may hold great potential, direct
      reprogramming of endogenous cardiac fibroblasts, which represent more than half
      of the cells in the heart, into functional cardiomyocytes in situ may be an
      alternative strategy by which to regenerate the heart. We and others demonstrated
      that functional cardiomyocytes can be directly generated from fibroblasts by
      using several combinations of cardiac-enriched factors in mouse and human. In
      vivo gene delivery of cardiac reprogramming factors generates new cardiac muscle
      and improved heart function after myocardial infarction in mouse. This article
      reviews recent progress in cardiac reprogramming research and discusses the
      perspectives and challenges of this new technology for future regenerative
      therapy. 

PMID- 24079416
TI  - Fast, label-free force spectroscopy of histone-DNA interactions in individual
      nucleosomes using nanopores.
AB  - Herein we report a novel approach for fast, label-free probing of DNA-histone
      interactions in individual nucleosomes. We use solid-state nanopores to unravel
      individual DNA/histone complexes for the first time and find that the unraveling
      time depends on the applied electrophoretic force, and our results are in line
      with previous studies that employ optical tweezers. Our approach for studying
      nucleosomal interactions can greatly accelerate the understanding of fundamental
      mechanisms by which transcription, replication, and repair processes in a cell
      are modulated through DNA-histone interactions, as well as in diagnosis of
      diseases with abnormal patterns of DNA and histone modifications. 

PMID- 24079417
TI  - Quantum process tomography quantifies coherence transfer dynamics in vibrational
      exciton.
AB  - Quantum coherence has been a subject of great interest in many scientific
      disciplines. However, detailed characterization of the quantum coherence in
      molecular systems, especially its transfer and relaxation mechanisms, still
      remains a major challenge. The difficulties arise in part because the
      spectroscopic signatures of the coherence transfer are typically overwhelmed by
      other excitation-relaxation processes. We use quantum process tomography (QPT)
      via two-dimensional infrared spectroscopy to quantify the rate of the elusive
      coherence transfer between two vibrational exciton states. QPT retrieves the
      dynamics of the dissipative quantum system directly from the experimental
      observables. It thus serves as an experimental alternative to theoretical models
      of the system-bath interaction and can be used to validate these theories. Our
      results for coupled carbonyl groups of a diketone molecule in chloroform, used as
      a benchmark system, reveal the nonsecular nature of the interaction between the
      exciton and the Markovian bath and open the door for the systematic studies of
      the dissipative quantum systems dynamics in detail. 

PMID- 24079418
TI  - Plasmodium gametocyte inhibition identified from a natural-product-based fragment
      library.
AB  - Fragment-based screening is commonly used to identify compounds with relatively
      weak but efficient localized binding to protein surfaces. We used mass
      spectrometry to study fragment-sized three-dimensional natural products. We
      identified seven securinine-related compounds binding to Plasmodium falciparum 2'
      deoxyuridine 5'-triphosphate nucleotidohydrolase (PfdUTPase). Securinine bound
      allosterically to PfdUTPase, enhancing enzyme activity and inhibiting viability
      of both P. falciparum gametocyte (sexual) and blood (asexual) stage parasites.
      Our results provide a new insight into mechanisms that may be applicable to
      transmission-blocking agents. 

PMID- 24079420
TI  - Vertically integrated shared learning models in general practice: a qualitative
      study.
AB  - BACKGROUND: The numbers of learners seeking placements in general practice is
      rapidly increasing as an ageing workforce impacts on General Practitioner
      availability. The traditional master apprentice model that involves one-to-one
      teaching is therefore leading to supervision capacity constraints. Vertically
      integrated (VI) models may provide a solution. Shared learning, in which multiple
      levels of learners are taught together in the same session, is one such model.
      This study explored stakeholders' perceptions of shared learning in general
      practices in northern NSW, Australia. METHODS: A qualitative research method,
      involving individual semi-structured interviews with GP supervisors, GP
      registrars, Prevocational General Practice Placements Program trainees, medical
      students and practice managers situated in nine teaching practices, was used to
      investigate perceptions of shared learning practices. A thematic analysis was
      conducted on 33 transcripts by three researchers. RESULTS: Participants perceived
      many benefits to shared learning including improved collegiality, morale,
      financial rewards, and better sharing of resources, knowledge and experience.
      Additional benefits included reduced social and professional isolation, and
      workload. Perceived risks of shared learning included failure to meet the
      individual needs of all learners. Shared learning models were considered
      unsuitable when learners need to: receive remediation, address a specific deficit
      or immediate learning needs, learn communication or procedural skills, be given
      personalised feedback or be observed by their supervisor during consultations.
      Learners' acceptance of shared learning appeared partially dependent on their
      supervisors' small group teaching and facilitation skills. CONCLUSIONS: Shared
      learning models may partly address supervision capacity constraints in general
      practice, and bring multiple benefits to the teaching environment that are
      lacking in the one-to-one model. However, the risks need to be managed
      appropriately, to ensure learning needs are met for all levels of learners.
      Supervisors also need to consider that one-to-one teaching may be more suitable
      in some instances. Policy makers, medical educators and GP training providers
      need to ensure that quality learning outcomes are achieved for all levels of
      learners. A mixture of one-to-one and shared learning would address the benefits
      and downsides of each model thereby maximising learners' learning outcomes and
      experiences.

PMID- 24079424
TI  - Functional anatomy and biomechanics of shoulder stability in the athlete.
AB  - Glenohumeral joint motion results from a complex interplay between static and
      dynamic stabilizers that require intricate balance and synchronicity. Instability
      of the shoulder is a commonly encountered problem in active populations,
      especially young athletes. The underlying pathoanatomy predisposing to further
      episodes and the needs of individual athletes must be considered in determining
      the most appropriate treatment.

PMID- 24079419
TI  - Nanotechnology in cancer therapy.
AB  - Cancer is one of the major causes of mortality worldwide and advanced techniques
      for therapy are urgently needed. The development of novel nanomaterials and
      nanocarriers has allowed a major drive to improve drug delivery in cancer. The
      major aim of most nanocarrier applications has been to protect the drug from
      rapid degradation after systemic delivery and allowing it to reach tumor site at
      therapeutic concentrations, meanwhile avoiding drug delivery to normal sites as
      much as possible to reduce adverse effects. These nanocarriers are formulated to
      deliver drugs either by passive targeting, taking advantage of leaky tumor
      vasculature or by active targeting using ligands that increase tumoral uptake
      potentially resulting in enhanced antitumor efficacy, thus achieving a net
      improvement in therapeutic index. The rational design of nanoparticles plays a
      critical role since structural and physical characteristics, such as size,
      charge, shape, and surface characteristics determine the biodistribution,
      pharmacokinetics, internalization and safety of the drugs. In this review, we
      focus on several novel and improved strategies in nanocarrier design for cancer
      therapy.

PMID- 24079425
TI  - Biomechanics of complex shoulder instability.
AB  - Identification and treatment of the osseous lesions associated with complex
      shoulder instability remains challenging. Further biomechanical testing is
      required to delineate critical defect values and determine which treatments
      provide improved glenohumeral joint stability for the various defect sizes, while
      minimizing the associated complications.

PMID- 24079426
TI  - Mechanics and pathomechanics in the overhead athlete.
AB  - Optimal performance of the overhead throwing task requires precise mechanics that
      involve coordinated kinetic and kinematic chains to develop, transfer, and
      regulate the forces the body needs to withstand the inherent demands of the task
      and to allow optimal performance. These chains have been evaluated and the basic
      components, called nodes, have been identified. Impaired performance and/or
      injury, the DTS, is associated with alterations in the mechanics that are called
      pathomechanics. They can occur at multiple locations throughout the kinetic
      chain. They must be evaluated and treated as part of the overall problem.
      Observational analysis of the mechanics and pathomechanics using the node
      analysis method can be useful in highlighting areas of alteration that can be
      evaluated for anatomic injury or altered physiology. The comprehensive kinetic
      chain examination can evaluate sites of kinetic chain breakage, and a detailed
      shoulder examination can assess joint internal derangement of altered physiology
      that may contribute to the pathomechanics. Treatment of the DTS should be
      comprehensive, directed toward restoring physiology and mechanics and optimizing
      anatomy. This maximizes the body's ability to develop normal mechanics to
      accomplish the overhead throwing task.

PMID- 24079427
TI  - Imaging instability in the athlete: the right modality for the right diagnosis.
AB  - The imaging evaluation of an athlete with glenohumeral instability encompasses
      multiple modalities, including radiography, CT, and MRI. There remains an overall
      lack of agreement and consistency among the orthopedic community regarding
      techniques used to quantify glenohumeral bone loss. When a high level of clinical
      suspicion remains, advanced imaging techniques are strongly recommended to ensure
      reliable and accurate assessment of defect size and location.

PMID- 24079428
TI  - Decision making in the in-season athlete with shoulder instability.
AB  - Shoulder instability in the in-season athlete can generally be managed
      nonoperatively during the season, except when specific contraindications are
      present, such as bone loss or involvement of the dominant limb in an overhead
      athlete. Brace wear, although advocated by many investigators, has no proven
      efficacy in reducing the number or frequency of in-season instability events.
      Arthroscopic approaches are used for both anterior and posterior instability,
      with rates of success similar to open approaches but with the advantage of
      improved postoperative range of motion. Return to play may be considered 6 month
      postoperatively for the nonthrowing athlete and 9 months postoperatively for the
      overhead-throwing athlete.

PMID- 24079429
TI  - Microinstability and internal impingement in overhead athletes.
AB  - A complex interplay exists between the static and dynamic stabilizers in the
      glenohumeral joint, especially in overheard athletes who need a shoulder
      hypermobile enough to perform overhead activity yet stable enough to prevent
      joint subluxation. Concomitant shoulder pathologies commonly occur in the setting
      of microinstability and internal impingement. Before any surgical intervention, a
      3- to 6-month course of conservative measures should first be attempted, with
      exercises focused on rotator cuff and scapular stabilizer strengthening combined
      with posterior capsule stretching. If surgery is needed, arthroscopic suture
      plication with treatment of concomitant lesions has been shown to provide the
      best clinical outcomes. 

PMID- 24079430
TI  - Arthroscopic management of the contact athlete with instability.
AB  - The shoulder is the most commonly dislocated joint in the body, with a greater
      incidence of instability in contact and collision athletes. In contact and
      collision athletes that have failed nonoperative treatment, the most important
      factors to consider when planning surgery are amount of bone loss (glenoid,
      humeral head); patient age; and shoulder hyperlaxity. Clinical outcomes,
      instability recurrence rate, and return to sport rate are not significantly
      different between arthroscopic suture anchor and open techniques. Lateral
      decubitus positioning with distraction and four portal (including seven-degree
      and 5-o'clock positions) techniques allow for 360-degree access to the glenoid
      rim, with placement of at least three sutures anchors below 3 o'clock for optimal
      results. In patients with significant glenoid bone loss (>20%-25%, inverted pear
      glenoid), open bone augmentation techniques are indicated and arthroscopic
      techniques are contraindicated.

PMID- 24079431
TI  - The Latarjet-Patte procedure for recurrent anterior shoulder instability in
      contact athletes.
AB  - The Latarjet-Patte procedure satisfies all of the requirements for treating
      recurrent anterior instability in contact athletes and is therefore their
      preferred management in this patient group.

PMID- 24079432
TI  - Shoulder instability with concomitant bone loss in the athlete.
AB  - Thorough evaluation of the athlete with persistent shoulder instability and
      appropriate use of imaging modalities, such as 3-dimensional computed tomography,
      can help quantify the severity of bony deficiency. Based on obtained imaging and
      examination, surgical and nonsurgical methods can be considered. In many
      situations both the humeral- and glenoid-sided bone loss must be addressed.
      Depending on the extent of bone loss, athletic demands, and surgeon experience,
      arthroscopic or open surgical options can provide shoulder stability and return
      athletes to their prior level of activity. 

PMID- 24079433
TI  - Pediatric and adolescent shoulder instability.
AB  - Instability of the shoulder is a common issue faced by sports medicine providers
      caring for pediatric and adolescent patients. A thorough history and physical
      examination can help distinguish traumatic instability from multidirectional or
      voluntary instability. A systematic understanding of the relevant imaging
      characteristics and individual patient disease and goals can help guide initial
      treatment. Given the high risk of recurrent instability, young, active patients
      who seek to return to competitive contact sports should consider arthroscopic
      stabilization after a first-time instability event. MDI should be treated
      initially with conservative rehabilitation. Patients who fail extensive
      conservative treatment may benefit from surgical stabilization. Arthroscopic
      techniques may now approach the results found from traditional open capsular
      shift procedures. Future studies should be designed to examine the outcomes in
      solely pediatric and adolescent populations after both conservative and operative
      treatment of shoulder instability.

PMID- 24079434
TI  - Posterior shoulder instability in the contact athlete.
AB  - Historically, posterior shoulder instability has been a challenging problem for
      contact athletes and orthopedic surgeons alike. A complete understanding of the
      normal shoulder anatomy and biomechanics and the pathoanatomy responsible for the
      instability is necessary for a successful clinical outcome. In addition, the
      surgeon must be familiar with the diagnostic imaging and physical examination
      maneuvers required for the correct diagnosis without missing any other concurrent
      abnormalities. This understanding will allow orthopedists to plan and execute the
      appropriate management, whether this may involve conservative or surgical
      intervention. The goal should always be to correct the abnormality and have the
      patient return to play with full strength and no recurrent instability.

PMID- 24079435
TI  - Posterior instability caused by batter's shoulder.
AB  - In summary, batter's shoulder is a rare and only recently recognized entity. This
      condition is posterior shoulder instability caused by a missed attempt at hitting
      a pitch, especially with an outside pitch. The lack of counterforce from hitting
      a ball produces increased forces imparted on the posterior capsulolabral complex
      of the lead shoulder during batting. If the player fails conservative management,
      she or he can undergo an arthroscopic posterior labral repair instead of
      debridement. After treatment, the player can expect to return to play after
      approximately 6 to 7 months. Initial results from a small, retrospective series
      demonstrate greater than 90% excellent results. These findings are similar to
      current literature for arthroscopic treatment of posterior instability, which
      reports success rates that range from 75% to 91%. Longer-term follow-up will be
      needed to determine the natural history and prognosis or batter's shoulder. Based
      on initial results, the authors predict good to excellent results for most
      players with batter's shoulder who undergo proper treatment. Additionally, with
      the exception of switch hitters, the nonthrowing arm is affected. This can also
      improve the athlete's return to play.

PMID- 24079436
TI  - Shoulder instability in ice hockey players: incidence, mechanism, and MRI
      findings.
AB  - Ice hockey is by definition a contact sport, making players at high levels prone
      to traumatic injuries. The most common cause of injury is from body checking or
      player contact. 1 A high incidence of concomitant Bankart and significant Hill
      Sachs lesions was seen in these professional athletes. These results suggest that
      a careful assessment and appropriate management of humeral bone loss may be
      crucial in order to obtain successful outcomes in this challenging group of
      athletes.

PMID- 24079437
TI  - From the unstable painful shoulder to multidirectional instability in the young
      athlete.
AB  - In conclusion, instability as a cause of shoulder pain in the young athlete is a
      difficult and often missed diagnosis. These young patients often seek treatment
      of shoulder pain but do not recall any episodes of shoulder instability. As a
      result, these uncommon, poorly described forms of instability are often
      misdiagnosed. A heightened clinical suspicion and an accurate, prompt diagnosis
      of instability is of paramount importance in this athletic group. It dictates
      appropriate treatment of the condition, avoids treatment delays and failure,
      provides better outcomes, and ensures timely return to play. UPS and MDI are two
      forms of this diagnosis. In UPS, patients at risk are young hyperlax athletes
      with a history of direct trauma or forceful overextension of the shoulder. They
      have shoulder pain that is described as deep anterior, reproduced with an
      anterior apprehension test and relieved with a relocation test. Soft tissue
      and/or bony lesions consistent with instability (observed on imaging or at
      arthroscopy) are necessary to confirm the diagnosis of UPS. Once the diagnosis is
      made, standard arthroscopic techniques with labrum reinsertion and/or
      anteroinferior capsule plication can lead to predictable good results and return
      to sport. In MDI, patients at risk are also young hyperlax athletes. However,
      these patients often do not have a history of trauma. They have shoulder pain
      that is often somewhat vague in location and is reproduced with a sulcus and/or
      hyper abduction test. Soft tissue and/or bony lesions consistent with instability
      are uncommon, with the exception of capsular laxity. The mainstay of treatment is
      physiotherapy rehabilitation. When surgery is necessary, open capsular shift and
      arthroscopic capsular plication are effective.

PMID- 24079438
TI  - Results of shoulder stabilization surgery in athletes.
AB  - Athletes, especially in contact and collision sports, are at risk for anterior
      and, less commonly, posterior glenohumeral instability. Studies have demonstrated
      that both types of instability can be successfully treated with surgery, using
      either open or arthroscopic techniques. For athletes with anterior instability,
      open stabilization has a slightly lower recurrence rate than arthroscopic
      stabilization. For posterior instability, arthroscopic techniques facilitate a
      higher rate of return to sport than open techniques. Throwing athletes have been
      shown to have a lower rate of return to sport after the surgical treatment of
      both anterior and posterior instability. 

PMID- 24079439
TI  - Management of the athlete with a failed shoulder instability procedure.
AB  - The athlete with a failed instability procedure requires a thoughtful and
      systematic approach to achieve a good outcome. Goals of treatment should be
      defined and realistic expectations should be set. Revision stabilization has a
      high rate of recurrent instability, low rates of return to play, and low clinical
      outcome scores. Fundamental to successful revision surgery is choosing the
      correct procedure. The decision is straightforward in athletes with clear factors
      that predict recurrence (significant glenoid bone loss, engaging Hill-Sachs
      lesions) because only a bony procedure can restore the articular arc of the
      glenoid. Arthroscopic revision Bankart repair may be appropriate in those
      athletes who have an obvious Bankart tear and no bone loss after a traumatic
      reinjury. The challenge for the shoulder surgeon is identifying the best surgery
      for the athlete who does not have such clear-cut indications. Each factor that
      has the potential to lead to a poor outcome needs to be collected and calculated.
      Patient factors (age, laxity, type and level of sport), injury factors (mechanism
      of injury, capsulolabral injury, glenoid bone loss, Hill-Sachs lesion), and
      technical factors (previous surgery performed, integrity of repair, scarring)
      must be integrated into the treatment algorithm. Based on this collection of
      factors, the shoulder surgeon should be prepared to provide the athlete with the
      surgery that provides the best chance to return to playing sports and the lowest
      risk of recurrent instability.

PMID- 24079440
TI  - Nonoperative and postoperative rehabilitation for glenohumeral instability.
AB  - The glenohumeral joint is an inherently unstable joint that relies on the
      interaction of the dynamic and static stabilizers to maintain stability.
      Disruption of this interplay or poor development of any of these factors may
      result in instability, pain, and a loss of function. Rehabilitation will vary
      based on the type of instability present and the key principles described.
      Whether a course of nonoperative rehabilitation is followed or the patient
      presents postoperatively, a comprehensive program designed to establish full ROM
      and balance capsular mobility, in addition to maximizing muscular strength,
      endurance, proprioception, dynamic stability, and neuromuscular control is
      essential. A functional approach to rehabilitation using movement patterns and
      sport-specific positions along with an interval sport program will allow a
      gradual return to athletics. The focus of the program should minimize the risk of
      recurrence and ensure that the patient can safely return to functional
      activities.

PMID- 24079442
TI  - Shoulder instability in the athlete. Preface.

PMID- 24079443
TI  - The editor's roundtable: hypertriglyceridemia.

PMID- 24079444
TI  - Comparison of clinical presentation, left ventricular morphology, hemodynamics,
      and exercise tolerance in obese versus nonobese patients with hypertrophic
      cardiomyopathy.
AB  - Obesity is independently associated with left ventricular (LV) hypertrophy and
      thus may be an important modifier of the hypertrophic cardiomyopathy (HC)
      phenotype. We examined if obesity modifies the clinical presentation, LV
      morphology, outflow hemodynamics, and exercise tolerance in HC. In this cross
      sectional study, 88 obese (body mass index [BMI] >=30 kg/m(2)) and 154 nonobese
      (BMI <30 kg/m(2)) patients from the Johns Hopkins HC clinic were compared with
      respect to a variety of clinical and LV echocardiographic measurements. Obese
      patients (36.4%) were more likely to report exertional dyspnea (p = 0.04) and
      chest pain (p = 0.002) and had greater prevalence of hypertension (p = 0.008). LV
      posterior wall thickness (p = 0.01) but not the septal wall (p >=0.21) was
      significantly greater in obese patients, resulting in an increased LV mass index
      (p = 0.003). No significant differences in LV systolic and diastolic functions
      were observed, but obesity was associated with higher LV stroke volume (p =
      0.03), inducible LV outflow tract gradients (p = 0.045), and chance of developing
      LV outflow tract obstruction during stress (p = 0.035). In multivariate analysis,
      BMI was associated with increased posterior (but not septal) wall thickness (beta
      = 0.15, p = 0.02) and LV mass index (beta = 0.18, p = 0.005), particularly in
      those with hypertension. Obesity was also associated with reduced exercise time
      and functional capacity, and BMI independently correlated with reduced exercise
      tolerance. In conclusion, obesity is associated with larger LV mass, worse
      symptoms, lower exercise tolerance, and labile obstructive hemodynamics in HC.
      The association with increased outflow tract gradients has particular importance
      as contribution of obesity to the pressure gradients may influence clinical
      decisions in labile obstructive HC. 

PMID- 24079445
TI  - Effect of statin drugs on thoracic aortic aneurysms.
AB  - Pharmacologic interventions for thoracic aneurysms remain poorly characterized.
      The results of a pilot study by our group suggested improved outcomes among
      patients with thoracic aortic aneurysm who were taking statins. In the present
      study, we undertook a comprehensive analysis of a larger cohort of patients from
      the Database of the Aortic Institute at Yale-New Haven Hospital. A total of 1,560
      patients met the inclusion criteria. The adverse events (i.e., death, dissection,
      or rupture) and surgery rates for patients with (n = 369, 24%) and without (n =
      1,191, 76%) statin therapy were compared. We evaluated 3 anatomic components of
      the aorta: root, ascending and arch, and descending and thoracoabdominal aortic
      aneurysms. A smaller proportion of the statin group had adverse events: overall,
      7% versus 15%; ascending and arch, 6% versus 15%; and descending and
      thoracoabdominal aortic aneurysms, 8% versus 20%. Also, a smaller proportion of
      statin patients required surgery: overall, 48% versus 60%; ascending and arch,
      51% versus 62%; and descending and thoracoabdominal aortic aneurysms, 36% versus
      59% (p <0.001 to 0.01). The protective effect of statins was seen in all
      segments, except the aortic root. Log-rank evaluation of the interval to an
      adverse event or surgery was longer among statin-treated patients (p <0.001).
      Logistic regression analysis found statin use, angiotensin receptor blocker use,
      and chronic obstructive pulmonary disease were associated with decreased adverse
      events, and statin use, angiotensin receptor blocker use, beta-blocker therapy,
      and age were associated with a decreased odds of requiring surgery. Multiple
      logistic regression analysis found only statins were associated with a decreased
      odds of an adverse event and that statins, coronary artery disease, and chronic
      obstructive pulmonary disease were associated with a decreased odds of undergoing
      surgery. In conclusion, these findings provide a medicinal option for the arsenal
      of treatment options for patients with aneurysms of the thoracic aorta. 

PMID- 24079446
TI  - The structure of winter phytoplankton in Lake Nero, Russia, a hypertrophic lake
      dominated by Planktothrix-like Cyanobacteria.
AB  - BACKGROUND: The permanent dominance of Planktothrix-like syanobacteria has been
      often reported for shallow eutrophic?hypertrophic lakes in central Europe in
      summer?autumn. However studies on phytoplankton growth under ice cover in
      nutrient-rich lakes are very scarce. Lake Nero provides a good example of the
      contrasting seasonal extremes in environmental conditions. Moreover, the
      ecosystem underwent a catastrophic transition from eutrophic to hypertrophic 2003
      05, with dominance of filamentous cyanobacteria in summer?autumn. Towards the end
      of the period of ice cover, there is an almost complete lack of light and oxygen
      but abundance in nutrients, especially ammonium nitrogen, soluble reactive
      phosphorus and total phosphorus in lake Nero. The aim of the present study was to
      describe species composition and abundance of the phytoplankton, in relation to
      the abiotic properties of the habitat to the end of winters 1999-2010. We were
      interested if Planktothrix-like syanobacteria kept their dominant role under the
      ice conditions or only survived, and how did the under-ice phytoplankton
      community differ from year to year. RESULTS: Samples collected contained 172
      algal taxa of sub-generic rank. Abundance of phytoplankton varied widely from
      very low to the bloom level. Cyanobacteria (Limnothrix, Pseudanabaena,
      Planktothrix) were present in all winter samples but did not always dominate.
      Favourable conditions included low winter temperature, thicker ice, almost
      complete lack of oxygen and high ammonium concentration. Flagellates belonging to
      Euglenophyta and Cryptophyta dominated in warmer winters, when phosphorus
      concentrations increased. CONCLUSION: A full picture of algal succession in the
      lake may be obtained only if systematic winter observations are taken into
      account. Nearly anoxic conditions, severe light deficiency and high concentration
      of biogenic elements present a highly selective environment for phytoplankton.
      Hypertrophic water bodies of moderate zone covered by ice in winter and dominated
      by Planktothrix - like syanobacteria in summer/autumn may follow several
      scenarios in the end of winter. It may be intense proliferation syanobacteria
      normally dominating in summer, or the switch to the other species like the
      euglenoids and cryptomonads flagellates, or almost total depletion of
      phytoplankton.

PMID- 24079447
TI  - Cobalt-catalyzed hydrofluorination of unactivated olefins: a radical approach of
      fluorine transfer.
AB  - Catalytic hydrofluorination of olefins using a cobalt catalyst was developed. The
      exclusive Markovnikov selectivity, functional group tolerance, and scalability of
      this reaction make it an attractive protocol for the hydrofluorination of
      olefins. A preliminary mechanistic experiment showed the involvement of a radical
      intermediate. 

PMID- 24079449
TI  - Recalibrating gender perception: face aftereffects and the perceptual
      underpinnings of gender-related biases.
AB  - Contemporary perceivers encounter highly gendered imagery in media, social
      networks, and the workplace. Perceivers also express strong interpersonal biases
      related to targets' gendered appearances after mere glimpses at their faces. In
      the current studies, we explored adaptation to gendered facial features as a
      perceptual mechanism underlying these biases. In Study 1, brief visual exposure
      to highly gendered exemplars shifted perceptual norms for men's and women's
      faces. Studies 2-4 revealed that changes in perceptual norms were accompanied by
      notable shifts in social evaluations. Specifically, exposure to feminine
      phenotypes exacerbated biases against hypermasculine faces, whereas exposure to
      masculine phenotypes mitigated them. These findings replicated across multiple
      independent samples with diverse stimulus sets and outcome measures, revealing
      that perceptual gender norms are calibrated on the basis of recent visual
      encounters, with notable implications for downstream evaluations of others. As
      such, visual adaptation is a useful tool for understanding and altering social
      biases related to gendered facial features.

PMID- 24079448
TI  - Survey of Brucella infection and malaria among Abattoir workers in Kampala and
      Mbarara Districts, Uganda.
AB  - BACKGROUND: Brucellosis is among the most widespread zoonotic infections
      estimated at 14% in Uganda. A cross-sectional study was conducted to estimate the
      sero-prevalence, risk factors of Brucella infection and malaria among abattoir
      workers. METHODS: A survey was conducted among 232 abattoir workers in main
      abattoirs of Kampala and Mbarara districts in February 2007. A pre-tested
      questionnaire captured socio-demographic and occupational data. Brachial vein
      blood was tested for Brucella using Microplate Agglutination Test (MAT) and
      Standard Tube Agglutination Test (STAT) with a cut off titre of 1:160, and giemsa
      stained blood slides for malaria. Data was analyzed in SPSS 17.0. RESULTS: Seven
      males (3%, n = 232) had malaria and dual brucella and Plasmodium falciparum
      malaria was found in one person. Brucella sero-positivity was 10% (95% CI 6 - 16;
      n = 232) with 12% (n = 161) in Kampala and 7% (n = 71) in Mbarara district. Non
      use of protective gear Odds ratio (OR 3.3, 95% CI (1.25 - 50) and working in the
      abattoir beyond 5 years OR 2.4 95% CI (1.4 - 5.6) were associated with increased
      risk of Brucella infection. Age, sex, religion, keeping animals and consumption
      of raw milk or products were not significant. CONCLUSIONS: Brucella infection is
      a real risk among abattoir workers and use of full protective gear reduced risk
      significantly. Sensitization and public health care programs are needed to
      control this emerging problem.

PMID- 24079450
TI  - Ethical issues in human reproduction: Protestant perspectives in the light of
      European Protestant and Reformed Churches.
AB  - Protestantism is not a centralized religion. It is composed by many independent
      Churches having different moral and ethical standards. This review concentrates
      on the ethical principles prevalent in most modern European Reformed Churches. It
      does not intend to discuss the ethical principles of many other Protestant
      Churches present mainly in the USA. The common foundations of Protestant theology
      are the "five sola ("Sola scriptura", Sola fide", "Sola gratia", Solus Christus
      or Solo Christo", "Soli deo gloria"). In opposition to the Catholic Church, no
      intermediary is needed between the Bible and the believer. As a consequence,
      Protestant Churches have no Magisterium, such as the Catholic Church. Therefore
      Protestant Churches cannot declare a certain position to be the "official
      position". Each Christian is personally responsible for all his acts, including
      his ethical behaviour. There is no complete unanimity among all Protestants on
      ethics or on any other issue. Human dignity, personal rights and self
      determination have to be respected in each ethical consideration. The
      supersession of the Old Mosaic Covenant (including traditional Jewish law or
      Halakhah, maintained in Catholicism) by the New Covenant and by Christian
      Theology has an important impact on Protestant ethics in reproductive medicine.
      In the New Covenant, the Protestants Churches did not maintain the mandatory
      obligation from the old Mosaic Covenant to be fruitful and to multiply: there is
      no divine obligation by God to procreate. As a consequence, contraception is not
      a sin and not unethical. The status of the embryo is the key for the ethical
      consideration of all methods used in reproductive medicine. Most representatives
      of modern Protestant theology and bioethics defend the opinion that the embryo is
      not an independent human being as is the newborn child. For most Protestant bio
      ethicists, as long as an embryo has no nervous system, no organs and no pain
      receptors, it cannot be seen as a human being sensu strictiori: the zygote is not
      yet a "human being". The ethical right to be protected prenatally increases
      gradually with the age and the development of the embryo. Following this so
      called gradualist interpretation, the early stages of an embryo merit ethically a
      special status: although they have already "human life", they are not yet a
      "human being". All ethical considerations in modern reproductive medicine
      discussed in this review are based on this concept of the status of the embryo.
      It depends largely on the acceptance or rejection of this special status of the
      embryo, if a Protestant considers a certain method in reproductive medicine to be
      ethical or unethical.

PMID- 24079451
TI  - Allosteric inactivation of a trypsin-like serine protease by an antibody binding
      to the 37- and 70-loops.
AB  - Serine protease catalytic activity is in many cases regulated by conformational
      changes initiated by binding of physiological modulators to exosites located
      distantly from the active site. Inhibitory monoclonal antibodies binding to such
      exosites are potential therapeutics and offer opportunities for elucidating
      fundamental allosteric mechanisms. The monoclonal antibody mU1 has previously
      been shown to be able to inhibit the function of murine urokinase-type
      plasminogen activator in vivo. We have now mapped the epitope of mU1 to the
      catalytic domain's 37- and 70-loops, situated about 20 A from the S1 specificity
      pocket of the active site. Our data suggest that binding of mU1 destabilizes the
      catalytic domain and results in conformational transition into a state, in which
      the N-terminal amino group of Ile16 is less efficiently stabilizing the oxyanion
      hole and in which the active site has a reduced affinity for substrates and
      inhibitors. Furthermore, we found evidence for functional interactions between
      residues in uPA's C-terminal catalytic domain and its N-terminal A-chain, as
      deletion of the A-chain facilitates the mU1-induced conformational distortion.
      The inactive, distorted state is by several criteria similar to the E*
      conformation described for other serine proteases. Hence, agents targeting serine
      protease conformation through binding to exosites in the 37- and 70-loops
      represent a new class of potential therapeutics. 

PMID- 24079452
TI  - Factors influencing time to diagnosis and initiation of treatment of endemic
      Burkitt Lymphoma among children in Uganda and western Kenya: a cross-sectional
      survey.
AB  - BACKGROUND: Survival rates for children diagnosed with Burkitt lymphoma (BL) in
      Africa are far below those achieved in developed countries. Late stage of
      presentation contributes to poor prognosis, therefore this study investigated
      factors leading to delays in BL diagnosis and treatment of children in Uganda and
      western Kenya. METHODS: Guardians of children diagnosed with BL were interviewed
      at the Jaramogi Oginga Odinga Teaching and Referral Hospital (JTRH) and Uganda
      Cancer Institute (UCI) from Jan-Dec 2010. Information on sociodemographics,
      knowledge, attitudes, illness perceptions, health-seeking behaviors and prior
      health encounters was collected using a standardized, pre-tested questionnaire.
      RESULTS: Eighty-two guardians were interviewed (20 JTRH, 62 UCI). Median "total
      delay" (1st symptoms to BL diagnosis) was 12.1 weeks [interquartile range (IQR)
      4.9-19.9] in Kenya and 12.9 weeks (IQR 4.3-25.7) in Uganda. In Kenya, median
      "guardian delay" (1st symptoms to 1st health encounter) and "health system delay"
      (1st health encounter to BL diagnosis) were 9.0 weeks (IQR 3.6-15.7) and 2.0
      weeks (IQR 1.6-5.8), respectively. Data on guardian and health system delay in
      Uganda were only available for those with < 4 prior health encounters (n = 26).
      Of these, median guardian delay was 4.3 weeks (range 0.7-149.9), health system
      delay 2.6 weeks (range 0.1-16.0), and total delay 10.7 weeks (range 1.7-154.3).
      Guardians in Uganda reported more health encounters than those in Kenya (median
      5, range 3-16 vs. median 3, range 2-6). Among Kenyan guardians, source of income
      was the only independent predictor of delay, whereas in Uganda, guardian delay
      was influenced by guardians' beliefs on the curability of cancer, health system
      delay, by guardians' perceptions of cancer as a contagious disease, and total
      delay, by the number of children in the household and guardians' role as
      caretaker. Qualitative findings suggest financial costs, transportation, and
      other household responsibilities were major barriers to care. CONCLUSIONS: Delays
      from symptom onset to BL treatment were considerable given the rapid growth rate
      of this cancer, with guardian delay constituting the majority of total delay in
      both settings. Future interventions should aim to reduce structural barriers to
      care and increase awareness of BL in particular and cancer in general within the
      community, as well as among health professionals.

PMID- 24079453
TI  - Understanding the magnetic anisotropy in a family of N2(3-) radical-bridged
      lanthanide complexes: density functional theory and ab initio calculations.
AB  - Density functional theory (DFT) and ab initio methods were used to investigate
      the influence of both intramolecular exchange coupling and single-ion anisotropy
      on the relaxation barriers of a series of N2(3-) radical-bridged lanthanide
      complexes [{[(Me3Si)2N]2(THF)Ln}2(MU-eta(2):eta(2)-N2)](-) (Ln = Gd(III) (1),
      Tb(III) (2), Dy(III) (3), Ho(III) (4), and Er(III) (5)) reported by Long and co
      workers. DFT calculations show that the exchange coupling between the lanthanide
      ions is very weak, but the Ln-N2(3-) coupling is strong for each complex.
      Moreover, the exchange couplings of Ln-N2(3-) are antiferromagnetic for Ln =
      Gd(III), Tb(III), Dy(III), and Ho(III) but ferromagnetic for Er(III) for the
      nearly orthogonal magnetic orbitals on Er(III) and N2(3-). Ab initio calculations
      show that both of the large magnetic anisotropy of single Tb fragment and the
      strong Tb-N2(3-) antiferromagnetic couplings lead to the largest energy barrier
      of complex 2. Although the energy barrier of a single Er fragment is the second
      largest, the relaxation barrier of complex 5 is only 36.0 cm(-1) due to the weak
      Er(III)-N2(3-) coupling. This study suggests that both intramolecular exchange
      coupling and single-ion anisotropy contribute greatly to the full relaxation
      barrier of lanthanide-based single-molecule magnets (SMMs), which expands the
      understanding of SMMs using only the giant-spin model. 

PMID- 24079454
TI  - Analysis of conservation priorities of Iberoamerican cattle based on autosomal
      microsatellite markers.
AB  - BACKGROUND: Determining the value of livestock breeds is essential to define
      conservation priorities, manage genetic diversity and allocate funds. Within- and
      between-breed genetic diversity need to be assessed to preserve the highest intra
      specific variability. Information on genetic diversity and risk status is still
      lacking for many Creole cattle breeds from the Americas, despite their distinct
      evolutionary trajectories and adaptation to extreme environmental conditions.
      METHODS: A comprehensive genetic analysis of 67 Iberoamerican cattle breeds was
      carried out with 19 FAO-recommended microsatellites to assess conservation
      priorities. Contributions to global diversity were investigated using alternative
      methods, with different weights given to the within- and between-breed components
      of genetic diversity. Information on Iberoamerican plus 15 worldwide cattle
      breeds was used to investigate the contribution of geographical breed groups to
      global genetic diversity. RESULTS: Overall, Creole cattle breeds showed a high
      level of genetic diversity with the highest level found in breeds admixed with
      zebu cattle, which were clearly differentiated from all other breeds. Within
      breed kinships revealed seven highly inbred Creole breeds for which measures are
      needed to avoid further genetic erosion. However, if contribution to
      heterozygosity was the only criterion considered, some of these breeds had the
      lowest priority for conservation decisions. The Weitzman approach prioritized
      highly differentiated breeds, such as Guabala, Romosinuano, Cr. Patagonico,
      Siboney and Caracu, while kinship-based methods prioritized mainly zebu-related
      breeds. With the combined approaches, breed ranking depended on the weights given
      to the within- and between-breed components of diversity. Overall, the Creole
      groups of breeds were generally assigned a higher priority for conservation than
      the European groups of breeds. CONCLUSIONS: Conservation priorities differed
      significantly according to the weight given to within- and between-breed genetic
      diversity. Thus, when establishing conservation programs, it is necessary to also
      take into account other features. Creole cattle and local isolated breeds retain
      a high level of genetic diversity. The development of sustainable breeding and
      crossbreeding programs for Creole breeds, and the added value resulting from
      their products should be taken into consideration to ensure their long-term
      survival.

PMID- 24079455
TI  - [Perinatal factors affecting the detection of otoacoustic emissions in vaginally
      delivered, healthy newborns, during the first 48 hours of life].
AB  - INTRODUCTION AND OBJECTIVES: Most hospitals perform neonatal hearing screening
      because it is a very useful procedure. Otoacoustic emissions are an ideal
      technique for this screening. We analyse the possible influence on screening
      results of some perinatal factors. MATERIALS AND METHODS: We collected
      retrospective data from 8,239 healthy newborns delivered vaginally at the
      maternity ward of our hospital. We compared multiple perinatal factors vs the
      results of otoacoustic emissions performed within the first 48 h of life, before
      discharge. RESULTS: A total of 6.4% of newborns had an abnormal response and
      failed the screening. Univariate and multivariate analysis showed a significant
      (P<.0001) positive relationship between breastfeeding and normal otoacoustic
      emissions (OR: 0.65). Another, less significant factor was female gender. The
      remaining variables, including origin, education or employment status of the
      mother, maternal smoking, dystocic delivery, presentation, need for
      resuscitation, preterm labour (34-36 weeks), weight, length and frequent maternal
      pathology, such as streptococcus detection, hypothyroidism, hypertension or
      diabetes, were not significant. CONCLUSIONS: Breastfeeding was the most important
      factor related to a normal response in otoacoustic emissions. It may improve
      final results and reduce the number of neonates who need to be rescheduled for a
      repeated test, as well as the associated anxiety and the possibility of losing
      patients during follow-up. These are major problems in neonatal hearing
      screening.

PMID- 24079456
TI  - Gibberellic acid acts as an agonist of steroidogenesis in male rats.
AB  - Testicular steroidogenesis has significant implication in male reproductive
      function. Although the effects of various signalling molecules on testicular
      functions have been studied earlier, the influence of the plant hormone
      gibberellic acid (GA3 ) on steroidogenesis has not been investigated. Acute (4 h)
      and subacute (15 days) studies using this compound through oral administration
      (150 MUg day(-1) ) to groups of normal and diabetic Wistar male rats were
      therefore carried out. Results indicate that (i) enhanced activity of
      steroidogenic markers 3beta-hydroxysteroid dehydrogenase (3beta-HSD), 17beta
      hydroxysteroid dehydrogenase (17beta-HSD), elevated tissue testosterone (T)
      content, increased steroidogenic acute regulatory protein (StAR) and androgen
      binding protein (ABP) levels with reduced lipid peroxidation and improved
      antioxidant defence in this treatment group of normal and diabetic rat testis,
      and (ii) elevated lipid peroxidation and diminished antioxidant defence, with
      insignificant change in 3beta-HSD and 17beta-HSD activity and testosterone level
      in acute treatment group of normal and diabetic rats testis, were noted. The
      observed increase in the activity of testicular 3beta-HSD and 17beta-HSD along
      with elevated testosterone content established GA3 as an inducer of
      steroidogenesis in rat.

PMID- 24079457
TI  - One-pot fluorescent labeling protocol for complex hydroxylated bioactive natural
      products.
AB  - Tagging of small bioactive molecules with a fluorophore is a highly sensitive
      method to trace their cellular activities through real-time visual information.
      Here we disclose a 7-nitrobenzo-2-oxa-1,3-diazole (NBD)-based, high-yielding, one
      pot labeling protocol for hydroxylated molecules using Yamaguchi coupling as the
      key reaction. This methodology was successfully applied on several sensitive and
      complex hydroxylated bioactive compounds including 7-deacetylazadiradione,
      simvastatin, camptothecin, andrographolide, cinchonine, beta-dihydroartemisinin,
      and azadirachtin A. Further, utility of this protocol was illustrated on the
      cytotoxic activity of azadiradione derivatives against several cancer cell lines
      through cell imaging of two qualified fluorescent probes. 

PMID- 24079458
TI  - A national study on nurses' retention in healthcare facilities in underserved
      areas in Lebanon.
AB  - BACKGROUND: Nursing shortages and maldistribution are priority issues for
      healthcare systems around the globe. Such imbalances are often aggravated in
      underserved areas, especially in developing countries. Despite the centrality of
      this issue, there is a dearth of studies that examine the retention of nurses in
      underserved areas in the Middle East Region. This study investigates the
      characteristic and the factors associated with the retention of nurses working in
      rural areas in Lebanon. METHODS: This study uses a non-experimental cross
      sectional design to survey nurses working in underserved areas of Lebanon.
      Underserved areas in Lebanon were identified using WHO definition. A total of 103
      health facilities (hospitals and primary healthcare centers) located in these
      areas were identified and all nurses working at these facilities received a copy
      of the survey questionnaire. The questionnaire included five sections:
      demographic, work-life, career plan, job satisfaction, and assessment of work
      environment. Analysis included univariate and bivariate (chi-square, Student's t
      test and ANOVA) tests to describe the respondents and examine the significance
      between nurses' characteristics and their intent to stay. A logistic regression
      model was constructed to identify factors associated with nurses' intent to stay
      in underserved areas. RESULTS: A total of 857 nurses from 63 Primary Healthcare
      (PHC) centers and hospitals responded to the questionnaire (75.5% response rate).
      Only 35.1% of nurses indicated their intent to stay in their current job over the
      coming one to three years. Surveyed nurses were most satisfied with relationship
      with co-workers and least satisfied with extrinsic rewards. Rural nurses working
      in PHC centers were more satisfied than their hospital counterparts on all
      aspects of work and had significantly higher intention to stay (62.5% compared to
      31.5% in hospitals, P < 0.001). Regression analysis revealed that nurses less
      likely to report intent to stay were younger, unmarried, with less years of work
      experience and were not working towards a higher degree. Analysis reveals a
      directly proportional relationship between nurses' reported job satisfaction and
      their intent to stay. CONCLUSION: This study reveals poor retention of nurses in
      rural and underserved areas in Lebanon, especially in the hospital sector. The
      status quo is disquieting as it reflects an unstable and dissatisfied nursing
      workforce. Developing targeted retention strategies for younger nurses and those
      working in hospitals as well as the offering of professional development
      opportunities and devising an incentive scheme targeting rural nurses is pivotal
      to enhance nurses' job satisfaction and retention in rural settings.

PMID- 24079459
TI  - Diversity by divergence: Solution-phase parallel synthesis of a library of N
      diversified 1-oxa-7-azaspiro[4.5]decan-2-yl-propanes and -butanes.
AB  - The synthesis of a 162-member compound library derived from a single precursor
      via a multistage divergence strategy is described. Divergence is sequentially
      introduced in three ways: (1) by early preparation of two separable spirocyclic
      diastereomers, (2) by elaboration of each spirocyclic diastereomer to a different
      scaffold using four Horner-Emmons-Wadsworth reagents, and (3) by employing three
      different modes of nitrogen diversification with each scaffold to afford the
      final compounds. This 2 diastereomers * 4 reagents * 3 modes of diversification
      strategy leads to 24 unique synthetic pathways that ultimately afforded, in
      parallel format, the 162-compound set.

PMID- 24079460
TI  - Generalized eigenvalue minimization for uncertain first-order plus time-delay
      processes.
AB  - This paper shows how to apply generalized eigenvalue minimization to processes
      that can be described by a first-order plus time-delay model with uncertain gain,
      time constant and delay. An algorithm to transform the uncertain first-order plus
      time delay model into a state-space model with uncertainty polyhedron is firstly
      described. The accuracy of the transformation is studied using numerical
      examples. Then, the uncertainty polyhedron is rewritten as a linear-matrix
      inequality constraint and generalized eigenvalue minimization is adopted to
      calculate a feedback control law. Case studies show that even if uncertainties
      associated with the first-order plus time delay model are significant, a stable
      feedback control law can be found. The proposed control is tested by comparing
      with a robust internal model control. It is also tested by applying it to the
      temperature control of air-handing units. 

PMID- 24079461
TI  - Toward a single-layer two-dimensional honeycomb supramolecular organic framework
      in water.
AB  - The self-assembly of well-defined 2D supramolecular polymers in solution has been
      a challenge in supramolecular chemistry. We have designed and synthesized a rigid
      stacking-forbidden 1,3,5-triphenylbenzene compound that bears three 4,4'
      bipyridin-1-ium (BP) units on the peripheral benzene rings. Three hydrophilic
      bis(2-hydroxyethyl)carbamoyl groups are introduced to the central benzene ring to
      suppress 1D stacking of the triangular backbone and to ensure solubility in
      water. Mixing the triangular preorganized molecule with cucurbit[8]uril (CB[8])
      in a 2:3 molar ratio in water leads to the formation of the first solution-phase
      single-layer 2D supramolecular organic framework, which is stabilized by the
      strong complexation of CB[8] with two BP units of adjacent molecules. The
      periodic honeycomb 2D framework has been characterized by various (1)H NMR
      spectroscopy, dynamic light scattering, X-ray diffraction and scattering,
      scanning probe and electron microscope techniques and by comparing with the self
      assembled structures of the control systems. 

PMID- 24079462
TI  - SenseCam reminiscence and action recall in memory-unimpaired people.
AB  - Case studies of memory-impaired individuals consistently show that reminiscing
      with SenseCam images enhances event recall. This exploratory study examined
      whether a similar benefit would occur for the consolidation of memories in memory
      unimpaired people. We tested delayed recall for atypical actions observed on a
      lengthy walk. Participants used SenseCam, a diary, or no external memory aid
      while walking, followed by reminiscence with SenseCam images, diary entries, or
      no aid, either alone (self-reminiscence) or with the experimenter (social
      reminiscence). One week later, when tested without SenseCam images or diary
      entries, prior social reminiscence produced greater recall than self
      reminiscence, but there were no differences between memory aid conditions for
      action free recall or action order recall. When methodological variables were
      controlled, there was no recall advantage for SenseCam reminiscence with memory
      unimpaired participants. The case studies and present study differ in multiple
      ways, making direct comparisons problematic. SenseCam is a valuable aid to the
      memory impaired, but its mnemonic value for non-clinical populations remains to
      be determined.

PMID- 24079463
TI  - Investigating the thermodynamics of UNCG tetraloops using infrared spectroscopy.
AB  - Using infrared (IR) absorption spectroscopy, we have explored the folding
      thermodynamics of the UNCG class of RNA hairpin tetraloops (N = U, A, C, or G).
      Without the need to introduce non-native probes, IR spectroscopy makes it
      possible to distinguish specific structural elements such as base pairing versus
      base stacking or loop versus stem motions. Our results show that different
      structural components exhibit different thermodynamics. Specifically, we have
      found that tetraloop melting proceeds in a thermally sequential fashion, where
      base pairing in the stem is disrupted before (i.e., at a lower temperature) base
      stacking along the entire chain. In addition, for N = A, our data argue that the
      structure immediately surrounding adenine is particularly stable and melts at a
      higher temperature than either base-pairing or base-stacking interactions. Taken
      together, these results suggest that hairpin loop formation is not a simple two
      state process, even in the equilibrium limit. 

PMID- 24079464
TI  - The relationship between sleep patterns and attention levels.
AB  - Fifty-nine adults slept five nights with an Actigraph and answered two
      questionnaires related to sleeping quality and morningness/eveningness
      preferences. Next they performed a computerized attention task (the mathematics
      continuous performance test (MATH-CPT)) to assess various measures of attention.
      Results showed significant correlations between six attention variables and two
      measures of sleep assessed by the Actigraph. Linear regression with sleep
      variables as independent variables, and measures of the computerized test as
      dependent variables showed that sleep measures explained 30% of the variance of
      the score in the "final attention formula" of the test, and 27% of the "rate of
      response." 

PMID- 24079466
TI  - Changes of gait kinematics in different simulators of reduced gravity.
AB  - Gravity reduction affects the energetics and natural speed of walking and
      running. But, it is less clear how segmental coordination is altered. Various
      devices have been developed in the past to study locomotion in simulated reduced
      gravity. However, most of these devices unload only the body center of mass. The
      authors reduced the effective gravity acting on the stance or swing leg to 0.16g
      using different simulators. Locomotion under these conditions was associated with
      a reduction in the foot velocity and significant changes in angular motion.
      Moreover, when simulated reduced gravity directly affected the swing limb, it
      resulted in significantly slower swing and longer foot excursions, suggesting an
      important role of the swing phase dynamics in shaping locomotor patterns.

PMID- 24079465
TI  - Vertebral fractures and self-perceived health in elderly women and men in a
      population-based cross-sectional study: the Tromso Study 2007-08.
AB  - BACKGROUND: Health-related quality of life (HRQL) may be associated with
      increased mortality in the elderly. The effect of prevalent vertebral fractures
      on HRQL in elderly women and men is not well described. The purpose of this study
      was to examine the association between prevalent vertebral fractures and back
      pain, neck pain, and HRQL in elderly women and men, and to study possible gender
      differences in the reported pain and HRQL. METHODS: Information on prevalent
      vertebral fractures was ascertained by a vertebral fracture assessment (VFA)
      method (dual-energy X-ray absorptiometry (DXA), GE Lunar Prodigy) in 2887 women
      and men, mean age 65.4 (SD 9.4) who participated in the population-based Tromso
      Study which was conducted in 2007-08. Bone mineral density (BMD; g/cm2) was
      measured by DXA at the femoral sites. Self-reported HRQL was assessed using the
      standardized measures EQ-5D-3 L and EQ VAS from the EuroQol Group. Lifestyle
      information was collected by questionnaires. The association between vertebral
      fractures and pain was analyzed using logistic regression, between vertebral
      fractures and EQ-5D-3 L and EQ VAS scores by multiple regression analyses.
      RESULTS: In women, presence of vertebral fractures was associated with an
      increased risk of back pain with an OR of 1.76 (95% CI: 1.24 - 2.50) after
      adjustments for age, height, weight, and BMD. Women with vertebral fractures had
      lower EQ-5D-3 L scores (p < 0.001) than women without vertebral fractures, also
      after adjustments. These associations were not present in men. Type of fracture
      was not associated with EQ-5D-3 L scores, but increasing numbers (p < 0.001) and
      severity of fractures (p < 0.002) were associated with decreasing EQ-5D-3 L score
      in women. CONCLUSION: Prevalent vertebral fractures are associated with increased
      risk of back pain and reduced HRQL in postmenopausal women, but not in men.

PMID- 24079467
TI  - Benzo-21-crown-7-based [1]rotaxanes: syntheses, X-ray crystal structures, and
      dynamic characteristics.
AB  - Two B21C7-based [1]rotaxanes were synthesized in high yields by means of
      copper(II)-mediated Eglinton coupling and a subsequent Pd/C-catalyzed reduction
      under H2. X-ray single-crystal analysis shows that [1]rotaxane takes on a self
      entangled conformation, wherein the macrocycle is threaded by its own tail.
      Moreover, it was found that [1]rotaxane with a flexible skeleton had more
      rotational motions than that of one with a rigid skeleton. 

PMID- 24079468
TI  - Euphorbia characias as bioenergy crop: a study of variations in energy value
      components according to phenology and water status.
AB  - Euphorbia characias has drawn much attention as a potential bioenergy crop given
      its considerable amount of latex, rich in hydrocarbon-like compounds, and its
      ability to grow in large areas of semiarid lands. Compositions of major
      constituents with an energy value have been determined for the three phenological
      stages of this plant (preflowering, flowering, and postflowering) and different
      irrigation treatments. Metabolites from both nonpolar and polar extracts have
      been identified and quantified by GC-MS, GC-FID, HPLC-ELSD, and UPLC-PDA-MS. The
      results highlight that the end of the flowering period is the optimal harvesting
      time to maximize the yields of E. characias as a potential energy crop. The total
      water requirements to obtain the maximum yields of hexane- and methanol
      extractables were determined for its annual development cycle. 

PMID- 24079469
TI  - Improving postoperative handover: a prospective observational study.
AB  - BACKGROUND: The information provided during the postoperative handover influences
      the delivery of care of patients in the postoperative recovery unit through their
      care on the ward. There is a need for a structured and systematic approach to
      postoperative handover. The aim of this study was to improve postoperative
      handover through the implementation of a new handover protocol, which involved a
      handover proforma and standardization of the handover process. METHODS: This
      prospective pre-post intervention study demonstrated the improvement in
      postoperative handover through standardization. There was a significant reduction
      in information omissions and task errors and improvement in communication and
      teamwork with the new handover protocol. RESULTS: There was a significant
      reduction in overall information omissions from 9 to 3 (P < .001) omissions per
      handover and task errors from 2.8 to .8 (P < .001) with the new handover
      protocol. Teamwork and nurses' satisfaction score significantly improved from a
      median of 3 to 4 (P < .001) and median of 4 to 5 (P < .001). Duration of handover
      decreased from a median of 8 to 7 minutes (P < .376). CONCLUSIONS: The study
      demonstrates that standardization of postoperative handover improved
      communication and teamwork and reduced information omissions and task errors.
      There was an improvement in the quality of the handover after the introduction of
      the new handover protocol, which was easy and simple to use.

PMID- 24079471
TI  - Does the ventriloquist illusion assist selective listening?
AB  - Driver (1996) reported that the ventriloquist illusion can enhance selective
      listening of speech. Participants in his study listened to target and distractor
      words from a single loudspeaker while watching lip movements of the target words
      on a video monitor either above the loudspeaker or displaced to the left or
      right. He found that participants were more accurate in repeating the target
      words when the video was displaced from the loudspeaker than when the video was
      directly above the loudspeaker. Driver proposed that the ventriloquist illusion
      dragged the target sounds toward the location of the lip movements, freeing them
      from interference from the distractor words. However, successful attempts at
      replicating this finding are rare (we know of only three successful replications
      from 19 attempts). In five experiments, we found a weak advantage for selective
      listening from displaced lip movements only when there was a convincing
      ventriloquist illusion. We conclude that the ventriloquist illusion is necessary
      to confer the advantage for selective listening from displaced lip movements but
      that the phenomenon is a fleeting one at best.

PMID- 24079470
TI  - A prospective case-control and molecular epidemiological study of human cases of
      Shiga toxin-producing Escherichia coli in New Zealand.
AB  - BACKGROUND: Shiga toxin-producing Escherichia coli (STEC) O157:H7 and related non
      O157 STEC strains are enteric pathogens of public health concern worldwide,
      causing life-threatening diseases. Cattle are considered the principal hosts and
      have been shown to be a source of infection for both foodborne and environmental
      outbreaks in humans. The aims of this study were to investigate risk factors
      associated with sporadic STEC infections in humans in New Zealand and to provide
      epidemiological information about the source and exposure pathways. METHODS:
      During a national prospective case-control study from July 2011 to July 2012, any
      confirmed case of STEC infection notified to regional public health units,
      together with a random selection of controls intended to be representative of the
      national demography, were interviewed for risk factor evaluation. Isolates from
      each case were genotyped using pulsed-field gel electrophoresis (PFGE) and Shiga
      toxin-encoding bacteriophage insertion (SBI) typing. RESULTS: Questionnaire data
      from 113 eligible cases and 506 controls were analysed using multivariate
      logistic regression. Statistically significant animal and environmental risk
      factors for human STEC infections were identified, notably 'Cattle livestock
      present in meshblock' (the smallest geographical unit) (odds ratio 1.89, 95% CI
      1.04-3.42), 'Contact with animal manure' (OR 2.09, 95% CI 1.12-3.90), and
      'Contact with recreational waters' (OR 2.95, 95% CI 1.30-6.70). No food
      associated risk factors were identified as sources of STEC infection. E. coli
      O157:H7 caused 100/113 (88.5%) of clinical STEC infections in this study, and
      97/100 isolates were available for molecular analysis. PFGE profiles of isolates
      revealed three distinctive clusters of genotypes, and these were strongly
      correlated with SBI type. The variable 'Island of residence' (North or South
      Island of New Zealand) was significantly associated with PFGE genotype (p =
      0.012). CONCLUSIONS: Our findings implicate environmental and animal contact, but
      not food, as significant exposure pathways for sporadic STEC infections in humans
      in New Zealand. Risk factors associated with beef and dairy cattle suggest that
      ruminants are the most important sources of STEC infection. Notably, outbreaks of
      STEC infections are rare in New Zealand and this further suggests that food is
      not a significant exposure pathway.

PMID- 24079472
TI  - All-atom force field for molecular dynamics simulations on organotransition metal
      solids and liquids. Application to M(CO)(n) (M = Cr, Fe, Ni, Mo, Ru, or W)
      compounds.
AB  - A previously developed OPLS-based all-atom force field for organometallic
      compounds was extended to a series of first-, second-, and third-row transition
      metals based on the study of M(CO)(n) (M = Cr, Fe, Ni, Mo, Ru, or W) complexes.
      For materials that are solid at ambient temperature and pressure (M = Cr, Mo, W)
      the validation of the force field was based on reported structural data and on
      the standard molar enthalpies of sublimation at 298.15 K, experimentally
      determined by Calvet-drop microcalorimetry using samples corresponding to a
      specific and well-characterized crystalline phase: Delta(sub)H(m) degrees  = 72.6
      +/- 0.3 kJ.mol(-1) for Cr(CO)(6), 73.4 +/- 0.3 kJ.mol(-1) for Mo(CO)(6), and 77.8
      +/- 0.3 kJ.mol(-1) for W(CO)(6). For liquids, where problems of polymorphism or
      phase mixtures are absent, critically analyzed literature data were used. The
      force field was able to reproduce the volumetric properties of the test set
      (density and unit cell volume) with an average deviations smaller than 2% and the
      experimentally determined enthalpies of sublimation and vaporization with an
      accuracy better than 2.3 kJ.mol(-1). The Lennard-Jones (12-6) potential function
      parameters used to calculate the repulsive and dispersion contributions of the
      metals within the framework of the force field were found to be transferable
      between chromium, iron, and nickel (first row) and between molybdenum and
      ruthenium (second row).

PMID- 24079474
TI  - The conventional management of male infertility.
AB  - Although the male reproductive function is impaired in about half of infertile
      couples, the evaluation of male infertility is underrated or neglected even
      today. In addition to a physical examination and imaging techniques, semen
      analysis as well as endocrine and genetic analyses should be part of the routine
      investigation. Few disorders have become subjects of rational treatment of the
      infertile male, even though, as examples, hypogonadotropic hypogonadism is
      treatable by gonadotropins and obstructive azoospermia by reconstructive surgery.
      Early treatment of maldescended testes and sexually transmitted diseases can
      prevent infertility. Similar pregnancy rates from patients with varicocele
      following surgery or counseling demonstrate the important role of the physician
      in the treatment of infertility. In the age of evidence-based medicine, most
      empirical treatments have been demonstrated to be ineffective. Instead,
      symptomatic treatment by assisted reproductive techniques has become a central
      tool to overcome otherwise untreatable male infertility. 

PMID- 24079473
TI  - MYC chromosomal aberration in differential diagnosis between Burkitt and other
      aggressive lymphomas.
AB  - Myc oncogenetic deregulation is abundantly described in several solid human
      cancer and lymphomas. Particularly, Burkitt's lymphoma belongs to the family of B
      Non Hodgkin aggressive lymphomas. Although it is morphologically characterized,
      immunophenotypic and cytogenetic diagnosis remains complex. In 2008, the WHO has
      introduced a new diagnostic class of aggressive B-cell lymphomas with features
      intermediate between BL and DLBCL. This diagnostic class represents a temporary
      container of aggressive B-cell lymphomas, not completely belonging to the BL and
      DLBCL categories. The importance of establishing a correct diagnosis would allow
      a better prognostic classification and a better therapeutic approach. In this
      review, we summarize the main diagnostic approaches necessary for appropriate
      diagnoses and we emphasize the importance of cytogenetic analysis of the oncogene
      Myc in the histopathological diagnosis and the prognostic/predictive
      stratification. In this contest, Myc represents the more involved gene in the
      development of these lymphomas. Therefore, we analyze the genetic aberrations
      causing its over-expression and the concomitant deregulation of molecular
      pathways related to it. We also propose a FISH approach useful in the diagnosis
      of these lymphomas. 

PMID- 24079475
TI  - Human chorionic gonadotropin as a measure of pregnancy duration.
AB  - OBJECTIVE: To compare gestational age (GA) estimates in early pregnancy,
      determined by last menstrual period (LMP), human chorionic gonadotropin (hCG)
      concentration, ultrasound crown-rump length (Hadlock formula), and ovulation day
      (luteinizing hormone surge plus 1day). METHODS: Female volunteers seeking to
      conceive (at 5 US sites) collected daily early-morning urine for up to 3
      menstrual cycles. Pregnant women underwent ultrasound dating scans. Conception
      cycle urine was quantitatively assessed for luteinizing hormone and hCG. Summary
      statistics for GA using each reference method were determined (n=131). RESULTS:
      Correlation between GA determined by ultrasound and ovulation day was excellent
      (maximum difference 10days); however, pregnancies dated by ultrasound were 3days
      advanced. The difference between LMP estimates and estimates based on ovulation
      day or ultrasound was 9 and 12days, respectively. A uniform rise in hCG on each
      day of pregnancy was seen using all reference methods. The accuracy of hCG
      measurement in determining the week since conception was more than 93%.
      CONCLUSION: Methods for establishing pregnancy duration vary in their accuracy
      and their GA estimates. The rise in hCG concentration in early pregnancy is
      uniform and therefore hCG levels provide the most accurate, early estimation of
      GA in single, viable pregnancies. ClinicalTrials.gov:NCT01077583.

PMID- 24079476
TI  - Genome-wide interval mapping using SNPs identifies new QTL for growth, body
      composition and several physiological variables in an F2 intercross between fat
      and lean chicken lines.
AB  - BACKGROUND: For decades, genetic improvement based on measuring growth and body
      composition traits has been successfully applied in the production of meat-type
      chickens. However, this conventional approach is hindered by antagonistic genetic
      correlations between some traits and the high cost of measuring body composition
      traits. Marker-assisted selection should overcome these problems by selecting
      loci that have effects on either one trait only or on more than one trait but
      with a favorable genetic correlation. In the present study, identification of
      such loci was done by genotyping an F2 intercross between fat and lean lines
      divergently selected for abdominal fatness genotyped with a medium-density
      genetic map (120 microsatellites and 1302 single nucleotide polymorphisms).
      Genome scan linkage analyses were performed for growth (body weight at 1, 3, 5,
      and 7 weeks, and shank length and diameter at 9 weeks), body composition at 9
      weeks (abdominal fat weight and percentage, breast muscle weight and percentage,
      and thigh weight and percentage), and for several physiological measurements at 7
      weeks in the fasting state, i.e. body temperature and plasma levels of IGF-I,
      NEFA and glucose. Interval mapping analyses were performed with the QTLMap
      software, including single-trait analyses with single and multiple QTL on the
      same chromosome. RESULTS: Sixty-seven QTL were detected, most of which had never
      been described before. Of these 67 QTL, 47 were detected by single-QTL analyses
      and 20 by multiple-QTL analyses, which underlines the importance of using
      different statistical models. Close analysis of the genes located in the defined
      intervals identified several relevant functional candidates, such as ACACA for
      abdominal fatness, GHSR and GAS1 for breast muscle weight, DCRX and ASPSCR1 for
      plasma glucose content, and ChEBP for shank diameter. CONCLUSIONS: The medium
      density genetic map enabled us to genotype new regions of the chicken genome
      (including micro-chromosomes) that influenced the traits investigated. With this
      marker density, confidence intervals were sufficiently small (14 cM on average)
      to search for candidate genes. Altogether, this new information provides a
      valuable starting point for the identification of causative genes responsible for
      important QTL controlling growth, body composition and metabolic traits in the
      broiler chicken.

PMID- 24079478
TI  - Copper-catalyzed Hiyama coupling of (hetero)aryltriethoxysilanes with
      (hetero)aryl iodides.
AB  - A Cu(I)-catalyzed Hiyama coupling was achieved, which proceeds in the absence of
      an ancillary ligand for aryl-heteroaryl and heteroaryl-heteroaryl couplings. A
      P,N-ligand is required to obtain the best product yields for aryl-aryl couplings.
      In addition to facilitating transmetalation, CsF is also found to function as a
      stabilizer of the [CuAr] species, potentially generated as an intermediate after
      transmetalation of aryltriethoxysilanes with Cu(I)-catalysts in the absence of
      ancillary ligands. 

PMID- 24079477
TI  - Non-high altitude methods for rapid screening of susceptibility to acute mountain
      sickness.
AB  - BACKGROUND: Acute mountain sickness (AMS) refers to the cerebral abnormalities
      typically triggered by exposure to hypobaric hypoxia at high altitude. Although
      AMS is not often life threatening, it can seriously impact health quality and
      decrease productivity. Thus, detection of potential susceptibility to AMS has
      become important for people arriving at high-altitude plateaus for the first
      time, including laborers and military staff. The aim of this review was to
      examine techniques which efficiently assess the susceptibility to AMS prior to
      exposure to high altitude. METHODS: By searching online databases, we retrieved
      studies with associations between AMS and methods to detect the susceptible
      people who were not exposed to high altitudes. Studies reporting significant
      correlation coefficients between screening methods and AMS scores were included.
      RESULTS: Several screening techniques of AMS susceptibility were found including
      cold pressor test, heart rate variability, and lung functions. Of these markers,
      heart rate variability was positively associated with AMS scores, while the rest
      were negatively associated with AMS scores. CONCLUSIONS: We identified three
      physiological markers that were significantly associated with the risk of AMS.
      Although it is well known that simple sea level tests are not really helpful in
      predicting AMS currently, these markers, to some degree, may be employed as
      references in predicting susceptibility.

PMID- 24079479
TI  - Effect of bone-marrow-derived mesenchymal stem cells on high-potential
      hepatocellular carcinoma in mouse models: an intervention study.
AB  - BACKGROUND: There are two completely contradictory views regarding the impact of
      human bone-marrow-derived mesenchymal stem cells (hMSCs) on hepatocellular
      carcinomas (HCCs). The aim of this study was to investigate the effect of hMSC
      engraftment on HCC tissues in nude mouse models, and assess the effect on
      metastatic potential of HCC. METHODS: hMSCs were engrafted into the nude mouse
      models of high metastatic HCC via the tail vein. The mice in the experimental
      group were engrafted with hMSCs (5 * 105 cells per mouse) via the tail vein 15
      days after inoculation of tumor cells, twice a week, while the animals in the
      control group were injected with hMSC culture medium (0.2 mL per mouse) via the
      tail vein. The subcutaneous tumor size was measured using an electronic digital
      caliper once every 4 days after hMSC engraftment. After 2, 3, 4, 5 and 6 weeks of
      tumor cell inoculation, the mice were killed and the tumors were collected in
      their entirety. The tumor weights and body weights of mice were measured, and the
      tumor inhibition rate was calculated. Quantitative real-time polymerase chain
      reaction (RT-PCR) was used to determine the expression of metastasis-related
      genes including osteopontin (OPN), bone sialoprotein (BSP) and integrin alpha5
      subunit (alpha-V) in the mouse models of high-metastatic HCC, and the expression
      of apoptosis-related genes including B cell lymphoma/leukemia-2 (Bcl2), Bcl-2
      associated X protein (Bax) and caspase 3 in tumor samples. RESULTS: The tumor
      weight inhibition rate was 26.62% at 2 weeks, 52.00% at 3 weeks, 38.20% at 4
      weeks, 31.98% at 5 weeks, and 30.23% at 6 weeks. Tumor tissue weight comparison
      results were significantly lower in the hMSC engraftment groups than in the
      control group at the second and third weeks. The expression of metastasis-related
      factors OPN, BSP and alpha-V gene was downregulated with time. The expression of
      antiapoptotic gene Bcl2 exhibited an obvious declining tendency, while the
      expression of apoptotic genes Bax and caspase 3 showed an obvious rising
      tendency. The expression of alpha-V and BSP significantly correlated positively
      with the expression of Bcl2, and negatively correlated with the expression of Bax
      and caspase 3. The tumor inhibition rate was not significantly correlated with
      the expression of antiapoptotic and apoptotic factors, and alpha-V and BSP
      factors, though it exhibited a significantly negative correlation with the
      expression of OPN. CONCLUSIONS: The highest tumor inhibition rate was observed 3
      weeks after hMSCs engraftment, and the tumor inhibition rate gradually reduced
      with the progression of time. The metastatic potential of tumor cells was
      downregulated after hMSC engraftment and hMSCs induce further tumor cells
      apoptosis. The decrease in the proliferation ability of tumor cells may induce a
      decline in metastatic potential in tumor cells.

PMID- 24079480
TI  - The dog that didn't growl: the interactional negotiation of momentary
      confabulations.
AB  - We examine from a discursive perspective momentary confabulations generated by
      patients in clinical interviews based on confabulation questionnaires. Commonly,
      neuropsychology treats such confabulations solely as evidence of patients'
      inabilities or deficits. Here we argue that patients' descriptions indicate the
      interaction of memory deficits with preserved interactional skills. More than
      this, however, patients' descriptions can be seen in part to arise out of the
      interviews themselves, in that the interviewer's turns (a) signal agreement
      rather than disagreement or challenge, and (b) lead to further development of
      descriptions instead of marking these out as problematic. These features mark out
      the clinical interviews as different from (i) everyday conversation, and (ii)
      other clinical settings such as the administration of verbal memory tests, and as
      a result the interviews allow scope for patients to develop unchallenged
      autobiographical narratives. Thus, ironically, interviews that rely on the
      standard use of confabulation questionnaires can provide settings that are
      especially conducive to the generation of the momentary confabulations that they
      aim to study.

PMID- 24079481
TI  - Electrophilic rearrangements of chiral amides: a traceless asymmetric alpha
      allylation.
AB  - A one-pot protocol for the asymmetric alpha-allylation reaction is reported
      relying on a key efficient asymmetric Claisen rearrangement, triggered by
      electrophilic activation of chiral pseudoephedrine amides. Subsequent reduction
      or hydrolysis of the resulting iminium ions provides highly enantioenriched alpha
      allylic aldehydes or carboxylic acids in a traceless manner. Compared to
      traditional alternatives which make use of strongly basic conditions, the work
      presented herein displays unprecedented functional group tolerance. 

PMID- 24079482
TI  - Pathological characteristics of the different stages of Acanthamoeba keratitis.
AB  - AIMS: To classify the clinical stages of Acanthamoeba keratitis (AK), and clarify
      the relationship between pathological changes and clinical features. METHODS AND
      RESULTS: Between January 2007 and May 2012, AK was diagnosed in 11 eyes by
      pathological examination and confocal laser scanning microscopy. Pathological
      investigation of all cornea samples from keratoplasty was done with periodic acid
      Schiff and haematoxylin and eosin stains. AK clinical stage, pathological
      features and postoperative treatment were studied retrospectively. The 11 cases
      were classified into development stage, convalescence stage, or cicatricial
      stage. In the development stage, marked conjunctival hyperaemia, a corneal
      epithelial defect, obvious corneal infiltration and progressive inflammation were
      seen; pathological changes comprised abundant inflammatory cells and a rounded
      cyst in the oedematous stroma, as well as a very small amount of
      neovascularization. In the convalescence cases, moderate conjunctival hyperaemia,
      corneal disciform structures, repair of the corneal epithelial defect and
      abundant neovascularization were seen; pathological changes included significant
      tissue necrosis and a small, shrunken cyst in the stroma, as well as significant
      neovascularization. In the cicatricial stage, keratoleukoma was seen;
      pathological changes comprised a few inflammatory cells and shrunken cysts
      scattered in the stroma. There were no cases of recurrence. CONCLUSIONS: The
      pathological features of different clinical stages confirmed the new clinical
      classification of AK.

PMID- 24079483
TI  - Insight into the molecular properties of Chitlac, a chitosan derivative for
      tissue engineering.
AB  - Chitlac is a biocompatible modified polysaccharide composed of a chitosan
      backbone to which lactitol moieties have been chemically inserted via a reductive
      N-alkylation reaction with lactose. The physical-chemical and biological
      properties of Chitlac that have been already reported in the literature suggest a
      high accessibility of terminal galactose in the lactitol side chain. This finding
      may account for its biocompatibility which makes it extremely interesting for the
      production of biomaterials. The average structure and the dynamics of the side
      chains of Chitlac have been studied by means of NMR (nuclear Overhauser effect
      and nuclear relaxation) and molecular dynamics to ascertain this hypothesis. A
      complete assignment of the (1)H and (13)C NMR signals of the modified
      polysaccharide has been accomplished together with the determination of the
      apparent pKa values of the primary and secondary amines (6.69 and 5.87,
      respectively). NMR and MD indicated a high mobility of Chitlac side chains with
      comparable average internuclear distances between the two techniques. It was
      found that the highly flexible lactitol side chain in Chitlac can adopt two
      distinct conformations differing in the orientation with respect to the
      polysaccharide chain: a folded conformation, with the galactose ring parallel to
      the main chain, and an extended conformation, where the lactitol points away from
      the chitosan backbone. In both cases, the side chain resulted to be highly
      hydrated and fully immersed in the solvent. 

PMID- 24079485
TI  - From good care to great welfare. Selected papers from the Detroit Zoological
      Society Symposium (August 2011).

PMID- 24079484
TI  - Total synthesis of (R)-sarkomycin via asymmetric rhodium-catalyzed conjugate
      addition.
AB  - (R)-Sarkomycin was prepared using a five-step total synthesis. Key steps in the
      enantioselective construction of the targeted scaffold were a rhodium-catalyzed
      asymmetric conjugate alkenyl addition with subsequent silyl trapping and a
      Mukaiyama aldol reaction with aqueous formaldehyde. Protection of the hydroxy
      group as a THP acetal and oxidative cleavage of the C,C-double bond provided a
      stable direct precursor to the natural product. The final liberation was carried
      out under slightly acidic conditions in a microwave-assisted reaction, resulting
      in a high yield of the "deceptive" sarkomycin. This represents the shortest
      enantioselective synthesis of this rather unstable compound to date and the first
      to employ asymmetric catalysis to introduce the stereogenic center. 

PMID- 24079486
TI  - Multidisciplinary approaches and assessment techniques to better understand and
      enhance zoo nonhuman animal welfare.
AB  - Nonhuman animal welfare is a complex concept that encompasses an animal's
      biological functioning, emotional states, and opportunities to experience a
      natural life, including the performance of natural behaviors. Further, animal
      welfare can be viewed as quality of life from the perspective of the animal and
      thus must consider the animal's subjective experiences. Therefore, assessing and
      enhancing animal welfare should include multidisciplinary, scientific ventures
      that strive to create a complete picture of how animals' bodies and minds respond
      to both aversive and pleasant situations. Practical assessment of animal welfare
      should include outcome-based measures from the animal that provide information
      about the individual's welfare as well as resource-based measures that can help
      identify causes of or risk factors for poor welfare. Increasingly, scientists are
      examining the emotional states of animals as well as the impact of pain,
      pleasure, and consciousness on animal welfare. This article discusses approaches
      such as preference testing, instrumental learning, examination of space and
      resource use, and qualitative assessments of animal welfare that might be useful
      and practical for assessing and enhancing welfare in zoo settings. 

PMID- 24079487
TI  - An epidemiological approach to welfare research in zoos: the Elephant Welfare
      Project.
AB  - Multi-institutional studies of welfare have proven to be valuable in zoos but are
      hampered by limited sample sizes and difficulty in evaluating more than just a
      few welfare indicators. To more clearly understand how interactions of husbandry
      factors influence the interrelationships among welfare outcomes, epidemiological
      approaches are needed as well as multifactorial assessments of welfare. Many
      questions have been raised about the housing and care of elephants in zoos and
      whether their environmental and social needs are being met in a manner that
      promotes good welfare. This article describes the background and rationale for a
      large-scale study of elephant welfare in North American zoos funded by the (U.S.)
      Institute of Museum and Library Services. The goals of this project are to
      document the prevalence of positive and negative welfare states in 291 elephants
      exhibited in 72 Association of Zoos and Aquariums zoos and then determine the
      environmental, management, and husbandry factors that impact elephant welfare.
      This research is the largest scale nonhuman animal welfare project ever
      undertaken by the zoo community, and the scope of environmental variables and
      welfare outcomes measured is unprecedented. 

PMID- 24079488
TI  - Hediger revisited: how do zoo animals see us?
AB  - Contact with people, both familiar (e.g., caretakers) and unfamiliar (e.g.,
      members of the public), is a significant part of the lives of nonhuman animals in
      zoos. The available empirical evidence shows that in many cases this contact
      represents a source of stress to the animals, although there is sufficient
      overall ambiguity in these studies to suggest that the effect of people on the
      animals is much more complex than this. A possible way to try to understand human
      animal relationships in the zoo is to ask how the animals might perceive the
      humans with whom they have contact, and here this question is explored further,
      using a framework first published by Hediger as a starting point. Hediger
      suggested that zoo animals might perceive people as an enemy, as part of the
      inanimate environment, or as a member of the same species. He supported these
      categories with anecdotal evidence, which was all that was available at the time,
      but more empirical evidence is available now, so it is appropriate to revisit
      these categories. The evidence suggests that animals discriminate both
      conspecific and heterospecific others, rather than just viewing familiar people
      as members of their own species, and that additional categories (stimulating part
      of the environment and friendship) may be warranted. These categories are then
      placed in a general model that suggests how relationships of different qualities,
      and hence different perceptions of each other, might develop between animals and
      the people they are in contact with in zoos. 

PMID- 24079489
TI  - Behavioral ecology of captive species: using behavioral adaptations to assess and
      enhance welfare of nonhuman zoo animals.
AB  - This project aimed to estimate a species' adaptations in nature and in captivity,
      assess welfare, suggest environmental changes, and find species characteristics
      that underlie welfare problems in nonhuman animals in the zoo. First, the current
      status of zoo animal welfare assessment was reviewed, and the behavioral ecology
      approach was outlined. In this approach, databases of species characteristics
      were developed using (a) literature of natural behavior and (b) captive behavior.
      Species characteristics were grouped in 8 functional behavioral ecological
      fitness-related categories: space, time, metabolic, safety, reproductive,
      comfort, social, and information adaptations. Assessments of the strength of
      behavioral adaptations in relation to environmental demands were made based on
      the results available from the literature. The databases with literature at the
      species level were coupled with databases of (c) behavioral observations and (d)
      welfare assessments under captive conditions. Observation and welfare assessment
      methods were adapted from the animal on the farm realm and applied to zoo
      species. It was expected that the comparison of the repertoire of behaviors in
      natural and captive environments would highlight welfare problems, provide
      solutions to welfare problems by environmental changes, and identify species
      characteristics underlying zoo animal welfare problems. 

PMID- 24079512
TI  - No direct by maternal effects interaction detected for pre-weaning growth in
      Romane sheep using a reaction norm model.
AB  - BACKGROUND: The pre-weaning growth of lambs, an important component of meat
      production, depends on maternal and direct effects. These effects cannot be
      observed directly and models used to study pre-weaning growth assume that they
      are additive. However, it is reasonable to suggest that the influence of direct
      effects on growth may differ depending on the value of maternal effects i.e. an
      interaction may exist between the two components. METHODS: To test this
      hypothesis, an experiment was carried out in Romane sheep in order to obtain
      observations of maternal phenotypic effects (milk yield and milk quality) and pre
      weaning growth of the lambs. The experiment consisted of mating ewes that had
      markedly different maternal genetic effects with rams that contributed very
      different genetic effects in four replicates of a 3 * 2 factorial plan. Milk
      yield was measured using the lamb suckling weight differential technique and milk
      composition (fat and protein contents) was determined by infrared spectroscopy at
      15, 21 and 35 days after lambing. Lambs were weighed at birth and then at 15, 21
      and 35 days. An interaction between genotype (of the lamb) and environment (milk
      yield and quality) for average daily gain was tested using a restricted
      likelihood ratio test, comparing a linear reaction norm model (interaction model)
      to a classical additive model (no interaction model). RESULTS: A total of 1284
      weights of 442 lambs born from 166 different ewes were analysed. On average, the
      ewes produced 2.3 +/- 0.8 L milk per day. The average protein and fat contents
      were 50 +/- 4 g/L and 60 +/- 18 g/L, respectively. The mean 0-35 day average
      daily gain was 207 +/- 46 g/d. Results of the restricted likelihood ratio tests
      did not highlight any significant interactions between the genotype of the lambs
      and milk production of the ewe. CONCLUSIONS: Our results support the hypothesis
      of additivity of maternal and direct effects on growth that is currently applied
      in genetic evaluation models.

PMID- 24079513
TI  - A kinetic safety gate controlling the delivery of unnatural amino acids to the
      ribosome.
AB  - Improving the yield of unnatural amino acid incorporation is an important
      challenge in producing novel designer proteins with unique chemical properties.
      Here we examine the mechanisms that restrict the incorporation of the fluorescent
      unnatural amino acid epsilonNH2-Bodipy576/589-lysine (BOP-Lys) into a model
      protein. While the delivery of BOP-Lys-tRNA(Lys) to the ribosome is limited by
      its poor binding to elongation factor Tu (EF-Tu), the yield of incorporation into
      peptide is additionally controlled at the step of BOP-Lys-tRNA release from EF-Tu
      into the ribosome. The unnatural amino acid appears to disrupt the interactions
      that balance the strength of tRNA binding to EF-Tu-GTP with the velocity of tRNA
      dissociation from EF-Tu-GDP on the ribosome, which ensure uniform incorporation
      of standard amino acids. Circumventing this potential quality control checkpoint
      that specifically prevents incorporation of unnatural amino acids into proteins
      may provide a new strategy to increase yields of unnatural polymers. 

PMID- 24079514
TI  - A novel SERCA inhibitor demonstrates synergy with classic SERCA inhibitors and
      targets multidrug-resistant AML.
AB  - Drug resistance exists as a major obstacle in the treatment of cancer, and drug
      molecules that retain effectiveness against resistant cancers are a high clinical
      priority. Ethyl 2-amino-6-(3,5-dimethoxyphenyl)-4-(2-ethoxy-2-oxoethyl)-4H
      chromene-3-carboxylate (CXL017) was recently identified as a promising lead for
      the treatment of multidrug-resistant leukemia, which elicits its cytotoxic
      effect, in part, through inhibition of the sarco/endoplasmic reticulum Ca(2+)
      ATPase (SERCA). Herein initial experiments with SERCA1a and CXL017 demonstrated
      no significant effect on calcium affinity, competed with ATP, and induced a dose
      dependent decrease in ATPase activity. Among all CXLs tested, (-)-CXL017
      exhibited the greatest SERCA inhibition with an IC50 = 13.5 +/- 0.5 MUM.
      Inhibitor combination studies were used to assess potential interactions between
      (-)-CXL017 and well-known SERCA inhibitors: thapsigargin, cyclopiazonic acid, and
      2,5-di-tert-butylhydroquinone. Surprisingly, (-)-CXL017 exhibited marked synergy
      with each of the known SERCA inhibitors, whereas all combinations of the known
      inhibitors yielded additive effects, indicating that (-)-CXL017 may bind at a
      unique allosteric site. Treatment of parental (HL60) and multidrug-resistant
      (HL60/MX2) acute myeloid leukemia cells with the known SERCA inhibitors revealed
      that all of these inhibitors demonstrate selective cytotoxicity (7.7-400-fold)
      for the resistant cell line. Within the CXL series, a positive correlation exists
      between SERCA inhibition and cytotoxicity in HL60/MX2 but not HL60. (-)-CXL017
      was also shown to enhance the cytotoxicity of thapsigargin in HL60/MX2 cells.
      Given the elevated SERCA levels and ER calcium content in HL60/MX2, SERCA likely
      plays a significant role in the collateral sensitivity of this multidrug
      resistance cell line to CXL molecules as well as known SERCA inhibitors. 

PMID- 24079515
TI  - Design or screening of drugs for the treatment of Chagas disease: what shows the
      most promise?
AB  - INTRODUCTION: Endemic in Latin America, Chagas disease is now becoming a serious
      global health problem, and yet has no financial viability for the pharmaceutical
      industry and remains incurable. In 2012, two antimycotic drugs inhibitors of
      fungal sterol 14alpha-demethylase (CYP51) - posaconazole and ravuconazole -
      entered clinical trials. Availability of the X-ray structure of the orthologous
      enzyme from the causative agent of the disease, protozoan parasite Trypanosoma
      cruzi, determined in complexes with posaconazole as well as with several
      experimental protozoa-specific CYP51 inhibitors opens an excellent opportunity to
      improve the situation. AREAS COVERED: This article summarizes the information
      available in PubMed and Google on the outcomes of treatment of the chronic Chagas
      disease. It also outlines the major features of the T. cruzi CYP51 structure and
      the possible structure-based strategies for rational design of novel T. cruzi
      specific drugs. EXPERT OPINION: There is no doubt that screenings for alternative
      drug-like molecules as well as mining the T. cruzi genome for novel drug targets
      are of great value and might eventually lead to groundbreaking discoveries.
      However, all newly identified molecules must proceed through the long, expensive
      and low-yielding drug optimization process, and all novel potential drug targets
      must be validated in terms of their essentiality and druggability. CYP51 is
      already a well-validated and highly successful target for clinical and
      agricultural antifungals. With minimal investments into the final stages of their
      development/trials, T. cruzi-specific CYP51 inhibitors can provide an immediate
      treatment for Chagas disease, either on their own or in combination with the
      currently available drugs.

PMID- 24079516
TI  - The shoulder and elbow joints and right and left sides demonstrate similar joint
      position sense.
AB  - Proper orientation of the shoulder and elbow is necessary for accurate and
      precise positioning of the hand. The authors' goal was to compare these joints
      with an active joint position sense task, while also taking into account the
      effects of joint flexion angle and arm dominance. Fifteen healthy subjects were
      asked to replicate presented joint angles with a single degree of freedom active
      positioning protocol. There were no significant differences in angular joint
      position sense errors with respect to joint (shoulder vs. elbow) and side (left
      vs. right). However, when considering linear positioning, errors were lower for
      the elbow, due to a shorter lever arm. Also, as flexion angles increased toward
      90 degrees , there was a consistent pattern of lower errors for both joints.

PMID- 24079517
TI  - Spontaneous gram-negative bacillary meningitis in adult patients: characteristics
      and outcome.
AB  - BACKGROUND: Spontaneous meningitis caused by gram-negative bacilli in adult
      patients is uncommon and poorly characterized. Our objective is to describe and
      compare the characteristics and the outcome of adult patients with spontaneous
      gram-negative bacilli meningitis (GNBM) and spontaneous meningitis due to other
      pathogens. METHODS: Prospective single hospital-based observational cohort study
      conducted between 1982 and 2006 in a university tertiary hospital in Barcelona
      (Spain). The Main Outcome Measure: In-hospital mortality. RESULTS: Gram-negative
      bacilli meningitis was diagnosed in 40 (7%) of 544 episodes of spontaneous acute
      bacterial meningitis. The most common pathogens were Escherichia coli and
      Pseudomonas species. On admission, characteristics associated with spontaneous
      gram-negative bacilli meningitis by multivariate modeling were advanced age,
      history of cancer, nosocomial acquisition of infection, urinary tract infection
      as distant focus of infection, absence of rash, hypotension, and a high
      cerebrospinal fluid white-cell count. Nine (23%) episodes were acquired in the
      hospital and they were most commonly caused by Pseudomonas. The in-hospital
      mortality rate was 53%. The mortality rate was higher among patients with Gram
      negative bacillary meningitis than among those with other bacterial meningitis
      and their risk of death was twenty times higher than among patients infected with
      Neisseria meningitidis (odds ratio 20.47; 95% confidence interval 4.03-103.93;
      p<0.001). CONCLUSIONS: Gram-negative bacilli cause 9% of spontaneous bacterial
      meningitis of known etiology in adults. Characteristics associated with GNBM
      include advanced age, history of cancer, nosocomial acquisition, and urinary
      tract infection as distant focus of infection. The mortality rate is higher among
      patients with gram-negative bacillary meningitis than among those with other
      bacterial meningitides.

PMID- 24079518
TI  - Prediction model for cadmium transfer from soil to carrot (Daucus carota L.) and
      its application to derive soil thresholds for food safety.
AB  - At present, soil quality standards used for agriculture do not fully consider the
      influence of soil properties on cadmium (Cd) uptake by crops. This study aimed to
      develop prediction models for Cd transfer from a wide range of Chinese soils to
      carrot (Daucus carota L.) using soil properties and the total or available soil
      Cd content. Path analysis showed soil pH and organic carbon (OC) content were the
      two most significant properties exhibiting direct effects on Cd uptake factor
      (ratio of Cd concentration in carrot to that in soil). Stepwise multiple linear
      regression analysis also showed that total soil Cd, pH, and OC were significant
      variables contributing to carrot Cd concentration, explaining 90% of the variance
      across the 21 soils. Soil thresholds for carrot (cultivar New Kuroda) cropping
      based on added or total Cd were then derived from the food safety standard and
      were presented as continuous or scenario criteria. 

PMID- 24079519
TI  - Sudden cardiac death among firefighters <=45 years of age in the United States.
AB  - Sudden cardiac death (SCD) is the leading cause of death in firefighters.
      Although on-duty SCD usually occurs in older victims almost exclusively because
      of coronary heart disease, no studies have examined causation across the career
      span. In the present retrospective case-control study, cases of SCD in young
      (aged <=45 years) firefighters from the National Institute for Occupational
      Safety and Health fatality investigations (n = 87) were compared with 2 age- and
      gender-matched control groups: occupationally active firefighters (n = 915) and
      noncardiac traumatic firefighter fatalities (n = 56). Of the SCD cases, 63% were
      obese and 67% had a coronary heart disease-related cause of death. The SCD
      victims had much heavier hearts (522 +/- 102 g) than noncardiac fatality controls
      (400 +/- 91 g, p <0.001). Cardiomegaly (heart weight >450 g) was found in 66% of
      the SCD victims and conveyed a fivefold increase (95% confidence interval [CI]
      1.93 to 12.4) in SCD risk. Furthermore, hypertension, including cases with left
      ventricular hypertrophy, increased SCD risk by 12-fold (95% CI 6.23 to 22.3)
      after multivariate adjustment. A history of cardiovascular disease and smoking
      were also independently associated with elevated SCD risk (odds ratio 6.89, 95%
      CI 2.87 to 16.5; and odds ratio 3.53, 95% CI 1.87 to 6.65, respectively). In
      conclusion, SCD in young firefighters is primarily related to preventable
      lifestyle factors. Obesity entry standards, smoking bans, and improved screening
      and/or wellness program are potential strategies to reduce SCD in younger
      firefighters. 

PMID- 24079521
TI  - 1,2-Dichlorohexafluoro-cyclobutane (1,2-c-C4F6Cl2, R-316c) a potent ozone
      depleting substance and greenhouse gas: atmospheric loss processes, lifetimes,
      and ozone depletion and global warming potentials for the (E) and (Z)
      stereoisomers.
AB  - The atmospheric processing of (E)- and (Z)-1,2-dichlorohexafluoro-cyclobutane
      (1,2-c-C4F6Cl2, R-316c) was examined in this work as the ozone depleting (ODP)
      and global warming (GWP) potentials of this proposed replacement compound are
      presently unknown. The predominant atmospheric loss processes and infrared
      absorption spectra of the R-316c isomers were measured to provide a basis to
      evaluate their atmospheric lifetimes and, thus, ODPs and GWPs. UV absorption
      spectra were measured between 184.95 to 230 nm at temperatures between 214 and
      296 K and a parametrization for use in atmospheric modeling is presented. The Cl
      atom quantum yield in the 193 nm photolysis of R-316c was measured to be 1.90 +/-
      0.27. Hexafluorocyclobutene (c-C4F6) was determined to be a photolysis co-product
      with molar yields of 0.7 and 1.0 (+/-10%) for (E)- and (Z)-R-316c, respectively.
      The 296 K total rate coefficient for the O((1)D) + R-316c reaction, i.e., O((1)D)
      loss, was measured to be (1.56 +/- 0.11) * 10(-10) cm(3) molecule(-1) s(-1) and
      the reactive rate coefficient, i.e., R-316c loss, was measured to be (1.36 +/-
      0.20) * 10(-10) cm(3) molecule(-1) s(-1) corresponding to a ~88% reactive yield.
      Rate coefficient upper-limits for the OH and O3 reaction with R-316c were
      determined to be <2.3 * 10(-17) and <2.0 * 10(-22) cm(3) molecule(-1) s(-1),
      respectively, at 296 K. The quoted uncertainty limits are 2sigma and include
      estimated systematic errors. Local and global annually averaged lifetimes for the
      (E)- and (Z)-R-316c isomers were calculated using a 2-D atmospheric model to be
      74.6 +/- 3 and 114.1 +/- 10 years, respectively, where the estimated
      uncertainties are due solely to the uncertainty in the UV absorption spectra.
      Stratospheric photolysis is the predominant atmospheric loss process for both
      isomers with the O((1)D) reaction making a minor, ~2% for the (E) isomer and 7%
      for the (Z) isomer, contribution to the total atmospheric loss. Ozone depletion
      potentials for (E)- and (Z)-R-316c were calculated using the 2-D model to be 0.46
      and 0.54, respectively. Infrared absorption spectra for (E)- and (Z)-R-316c were
      measured at 296 K and used to estimate their radiative efficiencies (REs) and
      GWPs; 100-year time-horizon GWPs of 4160 and 5400 were obtained for (E)- and (Z)
      R-316c, respectively. Both isomers of R-316c are shown in this work to be long
      lived ozone depleting substances and potent greenhouse gases.

PMID- 24079520
TI  - Congenital cardiac, aortic arch, and vascular bed anomalies in PHACE syndrome
      (from the International PHACE Syndrome Registry).
AB  - PHACE syndrome represents the association of large infantile hemangiomas of the
      head and neck with brain, cerebrovascular, cardiac, ocular, and ventral or
      midline defects. Cardiac and cerebrovascular anomalies are the most common
      extracutaneous features of PHACE, and they also constitute the greatest source of
      potential morbidity. Congenital heart disease in PHACE is incompletely described,
      and this study was conducted to better characterize its features. This study of
      the International PHACE Syndrome Registry represents the largest central review
      of clinical, radiologic, and histopathologic data for cardiovascular anomalies in
      patients with PHACE to date. Sixty-two (41%) of 150 subjects had intracardiac,
      aortic arch, or brachiocephalic vessel anomalies. Aberrant origin of a subclavian
      artery was the most common cardiovascular anomaly (present in 31 (21%) of 150
      subjects). Coarctation was the second most common anomaly, identified in 28 (19%)
      of 150 subjects, and can be missed clinically in patients with PHACE because of
      the frequent association of arch obstruction with aberrant subclavian origin.
      Twenty-three (37%) of 62 subjects with cardiovascular anomalies required
      procedural intervention. A greater percentage of hemangiomas were located on the
      left side of the head and neck in patients with coarctation (46% vs 39%);
      however, hemangioma distribution did not predict the presence of cardiovascular
      anomalies overall. In conclusion, PHACE is associated with a high risk of
      congenital heart disease. Cardiac and aortic arch imaging with detailed
      assessment of arch patency and brachiocephalic origins is essential for any
      patient suspected of having PHACE. Longitudinal investigation is needed to
      determine the long-term outcomes of cardiovascular anomalies in PHACE. 

PMID- 24079522
TI  - The cost-effectiveness of growth hormone replacement therapy (Genotropin(r)) in
      hypopituitary adults in Sweden.
AB  - BACKGROUND: To evaluate the cost-effectiveness of growth hormone (GH) treatment
      (Genotropin(r)) compared with no GH treatment in adults with GH deficiency in a
      Swedish societal setting. METHODS: A Markov-type cost-utility simulation model
      was constructed and used to simulate, for men and women, morbidity and mortality
      for GH-treated and -untreated individuals over a 20-year period. The calculations
      were performed using current available prices concerning morbidity-related
      healthcare costs and costs for Genotropin(r). All costs and treatment effects
      were discounted at 3%. Costs were expressed in Euro (1? = 9.03 SEK). GH-treated
      Swedish patients (n = 434) were identified from the KIMS database (Pfizer
      International Metabolic Database) and untreated patients (n = 2135) from the
      Swedish Cancer Registry and the Hospital Discharge Registry. RESULTS: The results
      are reported as incremental cost per quality-adjusted life year (QALY) gained,
      including both direct and indirect costs for GH-treated versus untreated
      patients. The weighted sum of all subgroup incremental cost per QALY was ?15,975
      and ?20,241 for men and women, respectively. Including indirect cost resulted in
      lower cost per QALY gained: ?11,173 and ?10,753 for men and women, respectively.
      Key drivers of the results were improvement in quality of life, increased
      survival, and intervention cost. CONCLUSIONS: The incremental cost per QALY
      gained is moderate when compared with informal thresholds applied in Sweden. The
      simulations suggest that GH-treatment is cost-effective for both men and women at
      the ?55,371 (SEK 500,000 - the informal Swedish cost-effectiveness threshold) per
      QALY threshold.

PMID- 24079523
TI  - Vascularized graft from the metatarsal base for reconstructing major
      osteochondral distal radius defects.
AB  - PURPOSE: To present our experience of reconstructing distal radius articular
      defects with a vascularized osteochondral graft from the metatarsal base and to
      present the mid-term outcomes. METHODS: Seven patients (average age, 36 y; range,
      26-55 y) who had reconstruction of major defects of the articular surface of the
      radius are presented. In 5, the lunate facet and sigmoid notch were
      reconstructed; in 1, an isolated defect on the surface of the lunate facet was
      reconstructed; and in 1, the scaphoid facet was reconstructed. In 6, the base of
      the third metatarsal was transferred, and in 1, the base of the second was
      transferred. RESULTS: All flaps survived without complications. At the latest
      follow-up (range, 20 mo to 8 y), the flexion-extension arc improved an average of
      50 degrees , and the pain on a visual analog scale decreased from 8 to 1 on
      average. Disabilities of the Arm, Shoulder, and Hand score improved from 54 to 11
      on average. One patient did not improve. No major complaints related to the donor
      site were mentioned (average American Orthopedic Foot and Ankle Society score of
      96/100). CONCLUSIONS: Our mid-term results are promising; however, the decision
      making process and the operation are complex. The operation is not indicated when
      the carpals are devoid of cartilage or when the defect involves the whole radius
      surface.

PMID- 24079524
TI  - Treatment of avascular proximal pole scaphoid nonunions with vascularized distal
      radius bone grafting.
AB  - PURPOSE: To investigate the outcomes of vascularized distal radius pedicled bone
      grafting secured with K-wires for scaphoid nonunions with small avascular
      proximal fragments. METHODS: We included patients with scaphoid nonunions and
      small, avascular proximal fragments that were too small for screw fixation. The
      mean size of the proximal pole fragments was 21% (range, 9% to 28%) of the entire
      scaphoid, based on quantitative radiographic measurement. All patients had distal
      radius bone grafting based on the 1,2-intercompartmental supraretinacular artery
      pedicle and fixation with K-wires. There were 21 wrists in 18 men and 2 women
      with the mean age of 34 years (range, 22 to 57 y). The mean duration of
      postoperative follow-up was 40 months (range, 12 to 103 mo). Radiographic union
      and clinical outcomes, including the ranges of wrist motion, grip strength, and
      the modified Mayo wrist score, were evaluated. RESULTS: Union was achieved in 18
      of 21 wrists (86%) at a mean time of 14 weeks after surgery (range, 8 to 28 wk).
      Nonunions with proximal fragments less than 20% of the total scaphoid healed in 6
      of 8 wrists. In a subset of these 8 wrists in which the proximal fragment was
      less than 15%, healing occurred in 2 of 4. The modified Mayo wrist score
      significantly improved from 46 to 78 points, and final wrist functions were rated
      as excellent in 5, good in 5, fair in 10, and poor in 1. Ranges of motion and
      grip strengths did not show significant changes after surgery. CONCLUSIONS:
      Vascularized distal radius bone grafting and K-wire fixation can heal scaphoid
      nonunions with small avascular proximal fragments, although motion and grip
      strength remain unchanged. Healing may be related to the size of the proximal
      pole fragment.

PMID- 24079525
TI  - Multiple intraneural glomus tumors on a digital nerve: case report.
AB  - Glomus tumors are soft-tissue tumors that are commonly found in the hand.
      Intraneural glomus tumors, however, are rare, and the few reported cases are
      mostly solitary tumors. We present a woman with a symptomatic swelling on her
      finger whose imaging findings suggested multiple tumors on the digital nerve,
      most compatible with a neuroma. Surgical excision and histology, however,
      confirmed the presence of multiple glomus tumors of the digital nerve. The
      patient's symptoms resolved after surgery. We describe the biology, typical
      presentation, and clinico-pathologic features of glomus tumors associated with a
      peripheral nerve and explore issues that the clinician should consider with
      multiple tumors. 

PMID- 24079526
TI  - Minimally invasive endoscopic decompression for anterior interosseous nerve
      syndrome: technical notes.
AB  - Anterior interosseous nerve syndrome (Nevin-Kiloh syndrome) is a rare entity
      caused by compression of the purely motor anterior interosseous nerve in the
      forearm. Historically, conventional surgical treatment has consisted of open
      decompression of the nerve. Unfortunately, open decompression is often
      complicated by scarring and significant morbidity. Endoscopic decompression is an
      alternative means of surgical intervention in the hands of well-trained surgeons
      comfortable with soft tissue endoscopy. In this report, we review relevant
      anatomy, offer technical hints, and present our personal experience with 4
      illustrative cases, all with greater than 1.5 years of follow-up. Our patients
      showed considerable improvement of their symptoms with minimal scarring. No
      significant complications occurred. 

PMID- 24079527
TI  - The role of magnetic resonance imaging in scaphoid fractures.
AB  - Fractures of the scaphoid are the most common surgically treated carpal fracture,
      and early diagnosis is critical to minimize complications including
      osteonecrosis. If the initial radiographs after the injury are inconclusive,
      early magnetic resonance imaging (MRI) provides an immediate diagnosis to allow
      for proper management. This has been shown to be cost effective both in direct
      measureable costs and likely in difficult-to-measure indirect costs related to
      lost productivity. In the cases in which no scaphoid fracture is present, MRI
      provides alternate diagnoses such as identification of other fractures (eg, other
      carpals and distal radius), osseous contusions, and soft tissue injuries
      (preferably >= 1.5T). When MRI is contraindicated, computed tomography (CT) is a
      reasonable alternative after the initial and repeat negative radiographs. MRI is
      the best imaging modality for assessing osteonecrosis of the proximal pole in a
      scaphoid nonunion. Unfortunately, the most useful imaging sequences remain
      controversial. My institution relies on the noncontrast T1-weighted images for
      the primary diagnosis of osteonecrosis with dynamic contrast enhancement used in
      a supplemental fashion. 

PMID- 24079528
TI  - The forearm squeeze test to identify a congenitally nonfunctioning flexor
      pollicis longus tendon.

PMID- 24079529
TI  - Superplot3d: an open source GUI tool for 3d trajectory visualisation and
      elementary processing.
AB  - When acquiring simple three-dimensional (3d) trajectory data it is common to
      accumulate large coordinate data sets. In order to examine integrity and
      consistency of object tracking, it is often necessary to rapidly visualise these
      data. Ordinarily, to achieve this the user must either execute 3d plotting
      functions in a numerical computing environment or manually inspect data in two
      dimensions, plotting each individual axis.Superplot3d is an open source MATLAB
      script which takes tab delineated Cartesian data points in the form x, y, z and
      time and generates an instant visualization of the object's trajectory in free
      rotational three dimensions. Whole trajectories may be instantly presented,
      allowing for rapid inspection. Executable from the MATLAB command line (or
      deployable as a compiled standalone application) superplot3d also provides simple
      GUI controls to obtain rudimentary trajectory information, allow specific
      visualization of trajectory sections and perform elementary
      processing.Superplot3d thus provides a framework for non-programmers and
      programmers alike, to recreate recently acquired 3d object trajectories in
      rotatable 3d space. It is intended, via the use of a preference driven menu to be
      flexible and work with output from multiple tracking software systems. Source
      code and accompanying GUIDE .fig files are provided for deployment and further
      development. 

PMID- 24079530
TI  - Agreement and concordance between married couples regarding family planning
      utilization and fertility intention in Dukem, Ethiopia.
AB  - BACKGROUND: Traditionally, women have been the main respondents for most of
      knowledge, attitude and practice survey related to family planning and fertility
      intention. However it is not well known how responses of women about husbands
      reflect the husband's attitude and practices. Thus this study is conducted to
      examine agreement of wife and husband regarding family planning use and fertility
      desire in Dukem, Ethiopia. METHODS: A community based cross sectional survey was
      conducted on 422 married couple's in Dukem town, central Ethiopia which were
      selected by using systematic sampling method. The study was conducted from
      November, 2010 to December, 2010. Data pertaining to fertility intentions and
      contraception was collected and the level of agreement (kappa statistics) between
      husbands and wives was computed. RESULT: The observed concordance was 71.6% for
      ideal family size, 94.9% for contraceptive attitude, 95.9% for fertility desire,
      and 99.7% for report of number of currently living children. The unadjusted kappa
      statistic varied from 0.61(p<=0.000) for contraceptive attitude to high of
      0.99(P<=0.000) for number of living children, for ideal family size
      0.63(P<=0.000), fertility desire 0.91(P<=0.000), ever use of contraceptive
      0.84(P<=0.000) and current use of contraceptive 0.87(P<=0.000) having kappa
      values in between. Overall greater degree of agreement was observed for
      reproductive health events as compared to family planning attitudes and
      intentions. CONCLUSION: In surveys pertaining to reproductive health events, the
      wife's response may be taken as proxy for the couple's response, but for
      assessing family planning attitudes and intentions, may require collecting
      information from husbands and wives separately.

PMID- 24079531
TI  - Chiral holmium complex-catalyzed Diels-Alder reaction of silyloxyvinylindoles:
      stereoselective synthesis of hydrocarbazoles.
AB  - The catalytic and asymmetric cycloaddition between 3-[1-(silyloxy)vinyl]indoles
      and electron-deficient olefins gave substituted hydrocarbazoles in up to 99%
      yield and 94% ee. This reaction was catalyzed by a novel chiral holmium(III)
      complex. Alkylation of the cycloadduct gave a tricyclic compound with four
      continuous chiral centers, one of which was a quaternary carbon. 

PMID- 24079532
TI  - Social class culture cycles: how three gateway contexts shape selves and fuel
      inequality.
AB  - America's unprecedented levels of inequality have far-reaching negative
      consequences for society as a whole. Although differential access to resources
      contributes to inequality, the current review illuminates how ongoing
      participation in different social class contexts also gives rise to culture
      specific selves and patterns of thinking, feeling, and acting. We integrate a
      growing body of interdisciplinary research to reveal how social class culture
      cycles operate over the course of the lifespan and through critical gateway
      contexts, including homes, schools, and workplaces. We first document how each of
      these contexts socializes social class cultural differences. Then, we demonstrate
      how these gateway institutions, which could provide access to upward social
      mobility, are structured according to middle-class ways of being a self and thus
      can fuel and perpetuate inequality. We conclude with a discussion of intervention
      opportunities that can reduce inequality by taking into account the contextual
      responsiveness of the self. 

PMID- 24079533
TI  - Effect of thyroid function on COPD exacerbation frequency: a preliminary study.
AB  - BACKGROUND: Frequent exacerbations of chronic obstructive pulmonary disease
      (COPD) have negative effects on quality of life and survival. Thus, factors
      related to exacerbations should be determined. We aimed to evaluate the effects
      of thyroid function on quality of life and exacerbation frequency in COPD
      patients. METHODS: The study population (n = 128) was divided into 3 groups
      (Group 1: COPD patients with hypothyroidism (n = 44); Group 2: COPD patients with
      normal thyroid function tests (n = 44); Group 3: Healthy subjects (n = 40)).
      Pulmonary function tests, maximum inspiratory pressure (MIP) and maximum
      expiratory pressure (MEP) measurements were performed. Quality of life
      questionnaire (Short Form 36, SF-36) was carried out. Patients were followed up
      for one year and number of exacerbations was recorded. RESULTS: FVC, FEV1/FVC,
      and FEF 25-75% measurements were statistically different between group 1 and 2 (p
      = 0.041, p = 0.001, p = 0.009 respectively). Although MEP values were
      significantly different between group 1 and 2 (p = 0.006), there was no
      significant difference in MIP values between groups (p = 0.77). Quality of life
      scores in group 1 and 2 were significantly lower than control group. Exacerbation
      frequency was significantly higher in group 1 than in group 2 (p = 0.017). TSH
      values and exacerbation frequency had positive correlation (p < 0.0001; r =
      0.82). CONCLUSIONS: The results of the present study suggest that thyroid
      function has an effect in exacerbation frequency of COPD. Decrease in
      exacerbation numbers with early detection of impairment in thyroid function will
      have positive contribution on quality of life in COPD patients.

PMID- 24079534
TI  - Li10SnP2S12: an affordable lithium superionic conductor.
AB  - The reaction of Li2S and P2S5 with Li4[SnS4], a recently discovered, good Li(+)
      ion conductor, yields Li10SnP2S12, the thiostannate analogue of the record holder
      Li10GeP2S12 and the second compound of this class of superionic conductors with
      very high values of 7 mS/cm for the grain conductivity and 4 mS/cm for the total
      conductivity at 27  degrees C. The replacement of Ge by Sn should reduce the raw
      material cost by a factor of ~3.

PMID- 24079535
TI  - WISC-IV unusual digit span performance in a sample of adolescents with learning
      disabilities.
AB  - Accurate identification of symptom magnification is essential when determining
      whether or not obtained test data are valid or interpretable. Apart from using
      freestanding symptom validity tests, many researchers encourage use of embedded
      measures of test-related motivation, including ones derived from the Digit Span
      subtest of the Wechsler scales. Such embedded measures are based on
      identification of performance patterns that are implausible if the test taker is
      investing full effort; however, it is unclear whether or not persons with
      preexisting cognitive difficulties such as specific learning disabilities (LD)
      might be falsely accused of poor test motivation due to actual but impaired
      working-memory skills. This study examined the specificity of such measures by
      reviewing performance of 86 adolescents with LDs on three measures embedded in
      the Wechsler Intelligence Scale for Children-Fourth Edition-namely, Digit Span
      (DS), Vocabulary-DS differences, and Reliable Digit Span (RDS) scores. Results
      indicate that while RDS is likely insensitive to impairments associated with LD,
      other DS measures may have an unacceptably high false-positive rate, especially
      if Canadian normative data are used to calculate scores. 

PMID- 24079536
TI  - Near-IR emissive chlorin-bacteriochlorin energy-transfer dyads with a common
      donor and acceptors with tunable emission wavelength.
AB  - Design, synthesis, and optical properties of a series of novel chlorin
      bacteriochlorin energy transfer dyads are described. Each dyad is composed of a
      common red-absorbing (645-646 nm) chlorin, as an energy donor, and a different
      near-IR emitting bacteriochlorin, as an energy acceptor. Each bacteriochlorin
      acceptor is equipped with a different set of auxochromes, so that each of them
      emits at a different wavelength. Dyads exhibit an efficient energy transfer
      (>=0.77) even for chlorin-bacteriochlorin pairs with large (up to 122 nm)
      separation between donor emission and acceptor absorption. Excitation of the
      chlorin donor results in relatively strong emission of the bacteriochlorin
      acceptor, with a quantum yield Phif range of 0.155-0.23 in toluene and 0.12-0.185
      in DMF. The narrow, tunable emission band of bacteriochlorins enables the
      selection of a series of three dyads with well-resolved emissions at 732, 760,
      and 788 nm, and common excitation at 645 nm. Selected dyads have been also
      converted into bioconjugatable N-succinamide ester derivatives. The optical
      properties of the described dyads make them promising candidates for development
      of a family of near-IR fluorophores for simultaneous imaging of multiple targets,
      where the whole set of fluorophores can be excited with the common wavelength,
      and fluorescence from each can be independently detected. 

PMID- 24079537
TI  - Influenza B-induced refractory cardiogenic shock: a case report.
AB  - BACKGROUND: An association between influenza A viruses and myocarditis was noted
      during the 1918 influenza pandemic. Since then, the link between the influenza B
      virus and fulminant myocarditis or cardiogenic shock has been rarely reported.
      CASE PRESENTATION: In February 2013, a 50 year-old-woman without known heart
      disease presented in profound cardiogenic shock with a left ventricular ejection
      fraction of 10%. Her presentation was preceded by six days of fever, chills,
      myalgia and fatigue. She had a junctional tachycardia, a troponin I of 12.6 ng/ml
      and her coronary angiography demonstrated normal coronary arteries. Percutaneous
      extracorporeal membrane oxygenation was required. An endotracheal aspirate at
      admission was positive for influenza B. All other respiratory, blood and urine
      cultures were negative. On day 7, a repeat echocardiography demonstrated
      significant recovery of left ventricular function with an ejection fraction of
      50%. She was later discharged home in good condition. CONCLUSIONS: Influenza B
      infection can be complicated by fulminant cardiomyopathy leading to cardiogenic
      shock in adults without preexisting cardiac disease.

PMID- 24079538
TI  - Interaction of neurodevelopmental pathways and synaptic plasticity in mental
      retardation, autism spectrum disorder and schizophrenia: implications for
      psychiatry.
AB  - OBJECTIVES: Schizophrenia (SCZ), autism spectrum disorder (ASD) and mental
      retardation (MR) are psychiatric disorders with high heritability. They differ in
      their clinical presentation and in their time course of major symptoms, which
      predominantly occurs for MR and ASD during childhood and for SCZ during young
      adult age. Recent findings with focus on the developmental neurobiology of these
      disorders emphasize shared mechanisms of common origin. These findings propose a
      continuum of genetic risk factors impacting on synaptic plasticity with MR
      causing impairments in global cognitive abilities, ASD in social cognition and
      SCZ in both global and social cognition. METHODS: We assess here the historical
      developments that led to the current disease concepts of the three disorders. We
      then analyse, based on the functions of genes mutated in two or three of the
      disorders, selected mechanisms shared in neurodevelopmental pathways and synaptic
      plasticity. RESULTS: The analysis of the psychopathological constructs supports
      the existence of three distinct clinical entities but also elaborates important
      associations. Similarly, there are common mechanisms especially in global and
      social cognition. CONCLUSIONS: We discuss implications from this integrated view
      on MR, ASD and SCZ for child & adolescent and adult psychiatry in pathophysiology
      and research perspectives.

PMID- 24079539
TI  - Arsenic speciation in rice cereals for infants.
AB  - The aim of this study was to conduct a survey of arsenic (As) content in rice
      cereals for infants. The analysis was based on the FDA Elemental Analysis Manual
      (EAM 4.11). An inductively coupled plasma mass spectrometer (ICP-MS) was used to
      determine total As. Due to the different toxicities of the chemical forms of
      arsenic, the ICP-MS coupled to a high-performance liquid chromatograph (HPLC) was
      used to perform As speciation. The total and speciated arsenic was determined in
      31 different infant rice cereals sold in U.S. supermarkets. The mass fraction of
      total inorganic As (iAs; sum of arsenite As(III) and arsenate As(V))
      concentrations ranged between 55.5 +/- 1.3 and 158.0 +/- 6.0 MUg/kg. The average
      total arsenic and iAs concentrations in infant rice cereal were 174.4 and 101.4
      MUg/kg, respectively. There was no substantial difference in iAs levels between
      organic and conventional rice cereals. The mixed-grain rice cereal contained the
      least total (105 MUg/kg) and inorganic arsenic (63 MUg/kg). The major detected
      organoarsenical species was dimethylarsinic acid (DMA). Monomethylarsonic acid
      (MMA) was not detected, or only trace levels were found. Spiked sample percent
      recoveries for iAs, DMA, and MMA ranged from a low of 97.3% for iAs to a high of
      115.0% for DMA. Results for speciated and total As in the National Institute of
      Standards and Technology standard reference material rice flour (NIST SRM 1568)
      were in good agreement with certified values. In the NIST SRM 1568 sample (n = 5)
      repeatability (%RSD) was 2.8% for iAs, 1.7% for DMA and species sum, and 5.3% for
      the total arsenic by As total method. The average percent mass balance was 99.9
      +/- 6.3% for the NIST SRM 1568 sample. This study provides new and much needed
      information on arsenic levels in rice-based infant cereals. 

PMID- 24079541
TI  - The Role of Matrix Metalloproteinases Polymorphisms in Age-Related Macular
      Degeneration.
AB  - BACKGROUND: Matrix metalloproteinases (MMP) are responsible for the degradation
      of extracellular matrix components and play an important role in the
      physiological and pathological remodeling of tissues. PURPOSE: To assess the
      impact of MMP-2 Rs2285053 (C->T), MMP-3 Rs3025039 (5A->6A), and MMP-9 Rs3918242
      (C->T) single nucleotide polymorphism on the development of early age-related
      macular degeneration (AMD). METHODS: The study group comprised 148 patients with
      AMD, and the control group enrolled 526 randomly selected persons. The genotyping
      of MMP-3 Rs3025039, MMP-2 Rs2285053, and MMP-9 Rs3918242 was performed by using
      the real-time PCR method. RESULTS: The frequency of the MMP-2 (-735) C/T and MMP
      3 (-1171) 5A/6A genotypes did not differ significantly between the patients with
      AMD and the control group, while the MMP-9 (-1562) C/C genotype was more
      frequently detected in patients with AMD than the control group (73.7% vs. 64.6%,
      p=0.048). Logistic regression analysis showed that the MMP-9 (-1562) C/C genotype
      increased the likelihood of developing early AMD (OR=1.51, 95% CI: 1.01-2.21;
      p=0.046). After the subdivision into the groups by age, a significant difference
      only in the frequency of the MMP-9 (-1562) C/C genotype was found comparing the
      AMD patients and the control group younger than 65 years (79.7% vs. 66.4%,
      p=0.039). CONCLUSIONS: Only MMP-9 Rs3918242 (C->T) single nucleotide polymorphism
      was found to play a significant role in the development of AMD, and the effect
      was more pronounced at the age of less than 65 years.

PMID- 24079542
TI  - Familial Moniliform Blepharosis: Clinical, Histopathological and Genetic
      Correlation.
AB  - BACKGROUND: Moniliform blepharosis is an ocular diagnostic feature of lipoid
      proteinosis, a rare autosomal recessive multisystem disorder with dermatological,
      otorhinolaryngological, ocular and neurological manifestations. Loss of function
      mutations in the extracellular matrix protein 1 (ECM1) gene have been identified
      as the causative factor, and their identification confirms the diagnosis. Until
      now, 41 different mutations have been described, the majority being nonsense and
      small insertions. Exon 6 and 7 are the most commonly involved. MATERIALS AND
      METHODS: Case report of an 8-year-old girl who presented with bilateral waxy
      papular lesions on the margins of the upper and lower lids since the age of 2
      years. RESULTS: Biopsy of the eyelid lesions showed replacement of the sub
      epidermal space by pink, PAS-positive and diastase resistant hyalinized material.
      Genetic testing of theECM1 gene showed a homozygous nonsense mutation c.1441C > T
      (p.Arg481X) in exon 10, confirming the diagnosis of lipoid proteinosis.
      CONCLUSIONS: Ophthalmologists may be the first physicians to encounter patients
      with lipoid proteinosis. The disease presents with protean symptoms, hence a
      careful examination with histopathology and genetic mutation analysis confirms
      the diagnosis, assisting in the counseling and management of patients.

PMID- 24079543
TI  - The discovery and development of boceprevir.
AB  - INTRODUCTION: Boceprevir was the first direct acting agent developed for the
      treatment of hepatitis C virus infection. Boceprevir functions by targeting NS3
      protease, a viral enzyme essential for replication. This peptidomimetic molecule
      was optimized from a peptide lead to provide a potent, selective and orally
      bioavailable drug that can be combined with ribavirin and peg interferon to
      achieve sustained viral response (undetectable HCV RNA levels for 24 weeks after
      completion of therapy) in patients infected with Genotype 1 of the virus. AREAS
      COVERED: This article provides a review of the pre-clinical and clinical
      discovery of boceprevir. This review includes the role and function of its
      molecular target, NS3 protease, as well as the assays used to measure in vitro
      efficacy, compound optimization and clinical studies to demonstrate safety and
      efficacy. EXPERT OPINION: As the first direct acting anti-HCV agent, boceprevir
      represents an important advance in therapy of this widespread chronic disease.
      Yet, while this therapy is a valuable approach, it does have limitations. Studies
      have suggested that 30% of patients do not achieve sustained viral response and
      11% of patients have developed anemia and/or neutropenia. Current drug discovery
      and development efforts are underway to develop novel therapeutic options that
      address these issues.

PMID- 24079540
TI  - The scoring of poses in protein-protein docking: current capabilities and future
      directions.
AB  - BACKGROUND: Protein-protein docking, which aims to predict the structure of a
      protein-protein complex from its unbound components, remains an unresolved
      challenge in structural bioinformatics. An important step is the ranking of
      docked poses using a scoring function, for which many methods have been
      developed. There is a need to explore the differences and commonalities of these
      methods with each other, as well as with functions developed in the fields of
      molecular dynamics and homology modelling. RESULTS: We present an evaluation of
      115 scoring functions on an unbound docking decoy benchmark covering 118
      complexes for which a near-native solution can be found, yielding top 10 success
      rates of up to 58%. Hierarchical clustering is performed, so as to group together
      functions which identify near-natives in similar subsets of complexes. Three set
      theoretic approaches are used to identify pairs of scoring functions capable of
      correctly scoring different complexes. This shows that functions in different
      clusters capture different aspects of binding and are likely to work together
      synergistically. CONCLUSIONS: All functions designed specifically for docking
      perform well, indicating that functions are transferable between sampling
      methods. We also identify promising methods from the field of homology modelling.
      Further, differential success rates by docking difficulty and solution quality
      suggest a need for flexibility-dependent scoring. Investigating pairs of scoring
      functions, the set theoretic measures identify known scoring strategies as well
      as a number of novel approaches, indicating promising augmentations of
      traditional scoring methods. Such augmentation and parameter combination
      strategies are discussed in the context of the learning-to-rank paradigm.

PMID- 24079545
TI  - Excitation spectra of large jet-cooled polycyclic aromatic hydrocarbon radicals:
      9-anthracenylmethyl (C15H11) and 1-pyrenylmethyl (C17H11).
AB  - The 9-anthracenylmethyl (C15H11) and 1-pyrenylmethyl (C17H11) radicals were
      identified by a combination of mass-resolved laser spectroscopy of a jet-cooled
      electrical discharge and quantum chemical methods. The 9-anthracenylmethyl
      radical was found to exhibit an origin band at 13757 cm(-1), with vibrational
      structure observed in a1 modes, and even quanta of b1 and a2 modes. The 1
      pyrenylmethyl radical was found to exhibit an origin band at 13,417 cm(-1), with
      a more complex vibrational structure as compared to 9-anthracenylmethyl, on
      account of its lower symmetry and larger size. The origin bands of these species
      were predicted to within 250 cm(-1) by fitting a linear relationship between
      observed origin wavelengths of similar chromophores and the calculated TD-B3LYP
      transition energies. A refined fit including the title radicals provides
      estimated absorption energies for the larger 2-perylenylmethyl and 6
      anthanthrenylmethyl species of 1.44 and 1.41 eV, respectively, with an estimated
      error of 30 meV.

PMID- 24079544
TI  - Transmigration route of Campylobacter jejuni across polarized intestinal
      epithelial cells: paracellular, transcellular or both?
AB  - Intact intercellular junctions and cellular matrix contacts are crucial
      structural components for the formation and maintenance of epithelial barrier
      functions in humans to control the commensal flora and protect against intruding
      microbes. Campylobacter jejuni is one of the most important zoonotic pathogens
      causing food-borne gastroenteritis and potentially more severe diseases such as
      reactive arthritis or Guillain-Barre syndrome. Crossing the intestinal epithelial
      barrier and host cell invasion by C. jejuni are considered to represent the
      primary reasons of gut tissue damage in humans and various animal model systems
      including monkeys, piglets, rabbits, hamsters and ferrets. C. jejuni is also able
      to invade underlying tissues such as the lamina propria, can enter the
      bloodstream, and possibly reach distinct organs such as spleen, liver or
      mesenteric lymph nodes. However, the molecular mechanisms as well as major
      bacterial and host cell factors involved in these activities are poorly
      understood. Various models exist by which the pathogen can trigger its own
      transmigration across polarized intestinal epithelial cells in vitro, the
      paracellular and/or transcellular mechanism. Recent studies suggest that
      bacterial factors such as flagellum, serine protease HtrA and lipooligosaccharide
      LOS may play an active role in bacterial transmigration. Here we review our
      knowledge on transmigration of C. jejuni as well as some other Campylobacter
      species, and discuss the pros and cons for the route(s) taken to travel across
      polarized epithelial cell monolayers. These studies provide fresh insights into
      the infection strategies employed by this important pathogen. 

PMID- 24079546
TI  - Cyclodextrin derivatives conjugated with aromatic moieties as pH-responsive drug
      carriers for anthracycline.
AB  - The modification of cyclodextrins (CDs) with side chains containing aromatic
      groups was found to lead to an increase of the stability of the complex with the
      anticancer drug doxorubicin (Dox). The formation constants evaluated by
      voltammetry were several orders of magnitude larger than that of the unmodified
      beta-CD ligand. For the CDs with aromatic moieties connected by linkers
      containing a triazole group, the formation constants of the complexes at pH 5.5
      and 7.4 were very different. At lower pH, binding was much weaker as a result of
      protonation of the triazole moiety in the linker. The drug was then released from
      the complex. Molecular modeling of the Dox-beta-CD system revealed different
      possible interactions between Dox and beta-CD. The observed pH dependence of the
      complex formation constant can be exploited for drug delivery to the targeted
      cells. The toxicities of the synthesized complexes and each of the complex
      components were tested by the MTT assay on two cell lines, the human lung
      carcinoma and human cervical cancer cell lines. 

PMID- 24079547
TI  - Separation of telechelic oligomers according to architecture by liquid
      chromatography.
AB  - Telechelic oligomers based on diethylene glycol or lower polyethylene glycols and
      caprolactone or butene oxide can be separated according to their architecture by
      means of liquid chromatography under adsorption conditions for the hydrophobic
      block and critical or exclusion conditions for PEG. This behavior, which is
      predicted by the theory, can be verified by the experiment for block copolymers
      of ethylene oxide with E-caprolactone and butene oxide. The individual peaks were
      identified by matrix-assisted time-of-flight mass spectrometry (MALDI-TOF-MS) of
      fractions obtained by semipreparative liquid chromatography at critical
      conditions of center block (PEG) and adsorption conditions for outer blocks (PCL
      and PBO). 

PMID- 24079548
TI  - Characterization of stationary phases based on polysiloxanes thermally
      immobilized onto silica and metalized silica using supercritical fluid
      chromatography with the solvation parameter model.
AB  - Stationary phases (SP) prepared by immobilization of polymers on silica or
      metalized silica are interesting for use in reversed-phase high-performance
      liquid chromatography (RP-HPLC) due to better protection of residual silanols or
      Lewis acid sites, as well as ease of preparation. On the other hand, there are no
      previous reports of the use of such phases in packed column supercritical fluid
      chromatography (SFC). Fourteen different SPs based on polysiloxanes (phenyl, C1,
      C8, C14, C18) thermally immobilized onto different supports (silica, titanized
      silica, zirconized silica) and one chemically bonded and end-capped C18
      stationary phase having a doubly zirconized silica support, were characterized
      with identical SFC conditions (CO2 with 10% of methanol, 25 degrees C, 15.0 MPa
      backpressure). Characterization was achieved based on retention factors measured
      for 85 test compounds and linear solvation energy relationships (LSER), namely
      the solvation parameter model based on Abraham descriptors. The polysiloxane SP
      were compared to a commercial C18-bonded silica (Kromasil C18), and to the native
      silica and metalized silica supports to better unravel the effects of stationary
      phase chemistry on chromatographic behavior. Together, 19 stationary phases were
      compared. The results highlight the variety of polarities provided by the column
      set. The polysiloxane backbone contributes significantly to the SP polarity as
      evidenced by the comparison to a classical alkylsiloxane-bonded SP. Metalization
      also appears to modify the polar characteristics of the SP, particularly toward
      basic compounds. Sample applications illustrate the applicability of these SP in
      SFC to the analysis of compounds of interest to the pharmaceutical and cosmetic
      industries.

PMID- 24079549
TI  - Separation of intact proteins by using polyhedral oligomeric silsesquioxane based
      hybrid monolithic capillary columns.
AB  - High-efficient separation of intact proteins is still a huge challenge in
      proteome analysis of complex biological samples by using capillary columns. In
      this study, four POSS-based hybrid monolithic capillary columns were prepared and
      applied in nano-flow liquid chromatography (Nano-LC) separation of intact
      proteins. It was observed that the POSS-based hybrid monolithic columns exhibit
      high permeability, good LC separation reproducibility and column efficiency for
      intact protein separation. The effects of different LC separation conditions such
      as flow rate, gradient steepness, column length and mobile phase additives on the
      LC separation efficiency of the POSS-based hybrid monolithic column were
      systematically examined. Finally, fast LC separation of 7 proteins mixture was
      realized in 2.5 min by using the optimized conditions on the 100 MUm i.d. POSS
      based hybrid monolithic capillary column.

PMID- 24079550
TI  - Portable microwave assisted extraction: An original concept for green analytical
      chemistry.
AB  - This paper describes a portable microwave assisted extraction apparatus (PMAE)
      for extraction of bioactive compounds especially essential oils and aromas
      directly in a crop or in a forest. The developed procedure, based on the concept
      of green analytical chemistry, is appropriate to obtain direct in-field
      information about the level of essential oils in natural samples and to
      illustrate green chemical lesson and research. The efficiency of this experiment
      was validated for the extraction of essential oil of rosemary directly in a crop
      and allows obtaining a quantitative information on the content of essential oil,
      which was similar to that obtained by conventional methods in the laboratory.

PMID- 24079551
TI  - Steady-state and non-steady state operation of counter-current chromatography
      devices.
AB  - Different variants of separation processes based on steady-state (continuous
      sample loading) and non-steady state (batch) operating modes of CCC columns have
      been analyzed and compared. The analysis is carried out on the basis of the
      modified equilibrium cell model, which takes into account both mechanisms of band
      broadening - interphase mass transfer and axial mixing. A full theoretical
      treatment of the intermittent counter-current chromatography with short sample
      loading time is performed. Analytical expressions are presented allowing the
      simulation of the intermittent counter-current chromatography separations for
      various experimental conditions. Chromatographic and extraction separations have
      been compared and advantages and disadvantages of the two methods have been
      evaluated. Further technical development of the CCC machines to implement counter
      current extraction separations is considered. 

PMID- 24079552
TI  - The sol-gel entrapment of noble metals in hybrid silicas: a molecular insight.
AB  - BACKGROUND: Why are metal nanoparticles sol-gel entrapped in ORMOSIL so active
      and stable? In other words, why ORMOSIL-entrapped metal nanoparticles are more
      active and selective than many heterogenized counterparts, including silica
      entrapped noble metals? RESULTS: Unveiling specific interactions between MNPs and
      the molecular structure of ORMOSIL, this work investigates subtle structural
      aspects through DRIFT spectroscopy. CONCLUSIONS: The results point to
      interactions between entrapped Pd and Pt nanocrystallites with the organosilica
      sol-gel cages similar to those taking place in enzymes.

PMID- 24079553
TI  - Pharmacokinetics and biodistribution of the cyclin-dependent kinase inhibitor 
      CR8- in mice.
AB  - BACKGROUND: CR8 is a second generation inhibitor of cyclin-dependent kinases
      derived from roscovitine. CR8 was shown to be 50-100 fold more potent than
      roscovitine in inducing apoptosis in different tumor cell lines. In the present
      investigation, we have established an analytical method for the quantification of
      CR8 in biological samples and evaluated its bioavailability, biodistribution and
      pharmacokinetics in mice. METHODS: A liquid chromatography method utilizing UV
      detection was used for the determination of CR8. CR8 was administered either
      orally (100 mg/kg) or i.v. (50 mg/kg) and the animals were sacrificed at
      different time points. Blood samples and organs were collected, after which the
      pharmacokinetic parameters were calculated for plasma and organs. RESULTS: CR8
      was eluted at 5 minutes in the high performance liquid chromatography system
      used. The LLOQ detection was 0.10 MUg/ml and linearity was observed within the
      0.10-10 MUg/ml range (r2 > 0.998). The accuracy and precision were >86%, while
      the recovery from plasma was >95%. CR8 was stable for 2 months at room
      temperature in both solution and plasma. CR8 pharmacokinetics was fitted to a two
      compartment open model after oral administration and to a one compartment model
      after i.v. injection. The elimination half-life was about 3 hours. Organ exposure
      to CR8 (expressed as % AUC organ vs. AUC plasma) was highest in liver (205%),
      adipose tissue (188%) and kidney (150%) and low in bone marrow (30%) and brain
      (15%) as compared to plasma. The oral bioavailability of CR8 was found to be
      essentially 100%. CONCLUSIONS: We have developed a rapid and simple method for
      the analysis of CR8. CR8 pharmacokinetics pattern showed 100% bioavailability,
      long half-life and limited distribution to brain and bone marrow, which may allow
      systemic exposure higher than the IC50 reported for cell death in tumor cell
      lines. CR8 displays favorable pharmacological properties and is therefore a good
      candidate for future clinical studies.

PMID- 24079554
TI  - The thermal effects of lavage on 57 ox femoral heads prepared for hip resurfacing
      arthroplasty.
AB  - BACKGROUND AND PURPOSE: Previously, we have documented surface temperatures
      recorded by thermography great enough to cause osteonecrosis of the femoral head
      during hip resurfacing. We now performed an in vitro investigation with 3
      questions: (1) whether water irrigation reduced bone surface temperature, (2)
      whether external bone temperatures were similar to core temperatures, and (3)
      whether blunting of the reamer affected temperature generation. METHODS: Using an
      ox-bone model, 57 femoral heads were peripherally reamed. The surface
      temperatures of bone were measured using a thermal camera and internal bone
      temperatures were measured using 2 theromocouples. We measured the effects of
      cooling with water at room temperature and with ice-cooled water. Progressive
      blunting of reamers was assessed over the 57 experiments. RESULTS: Mean and
      maximum temperatures generated during peripheral reaming were greater when no
      irrigation was used. Ice-cold saline protected femoral heads from thermal damage.
      External bone temperatures were much greater than internal temperatures, which
      were not sufficiently elevated to cause osteonecrosis regardless of lavage.
      Blunting of the reamer was not found to have a statistically significant effect
      in this study. INTERPRETATION: Cooling with ice-cooled water is recommended.
      Internal bone temperatures are not elevated despite the high surface temperatures
      reached during femoral head resurfacing.

PMID- 24079555
TI  - Effect of relative humidity on onset of capillary forces for rough surfaces.
AB  - Atomic force microscopy (AFM) was used to investigate the effect of relative
      humidity (RH) on the adhesion forces between silicon nitride AFM probes,
      hydrophilic stainless steel, and hydrophobic Perspex(r) (polymethylmethacrylate,
      PMMA). In addition, AFM-based phase contrast imaging was used to quantify the
      amount and location of adsorbed water present on these substrates at RH levels
      ranging from 15% to 65% at 22 degrees C. Both the adhesion forces and the
      quantities of adsorbed moisture were seen to vary with RH, and the nature of this
      variation depended on the hydrophobicity of the substrate. For the Perspex(r),
      both the adhesion force and the amount of adsorbed moisture were essentially
      independent of RH. For the stainless steel substrate, adsorbed moisture increased
      continuously with increasing RH, while the adhesion force rose from a minimum at
      15% RH to a broad maximum between 25% and 35% RH. From 35% to 55% RH, the
      adhesion force dropped continuously to an intermediate level before rising again
      as 65% RH was approached. The changes in adhesion force with increasing relative
      humidity in the case of the stainless steel substrate were attributed to a
      balance of effects associated with adsorbed, sub-continuum water on the
      cantilever and steel. Hydrogen bonding interactions between these adsorbed water
      molecules were thought to increase the adhesion force. However, when significant
      quantities of molecular water adsorbed, these molecules were expect to decrease
      adhesion by screening the van der Waals interactions between the steel and the
      cantilever tip, and by increasing the separation distance between these solid
      surfaces when they were 'in contact'. Finally, the slight increase in adhesion
      between 55% and 65% RH was attributed to true capillary forces exerted by
      continuum water on the two solid surfaces. 

PMID- 24079556
TI  - Brown-Vialetto-Van Laere syndrome: clinical and neuroradiological findings of a
      genetically proven patient.
AB  - The Brown-Vialetto-Van Laere syndrome (BVVLS) is a rare neurological disorder
      characterized by progressive pontobulbar palsy, sensorineural deafness and mixed
      spinal and upper motor neuropathy. Mutations in the C20orf54 gene have been
      linked to the disease and recently we reported the first Italian case of a BVVLS
      family with an intriguing C20orf54 genotype. However, the pathomechanisms
      underlying BVVLS are still unknown. Here we present the particular disease course
      with partial response to immunosuppressive therapy of our BVVLS patient for whom
      we hypothesize that dysimmune factors may have played a role in disease
      physiopathology.

PMID- 24079557
TI  - An implant-supported overdenture design with a horizontal path of insertion.
AB  - The rehabilitation of the atrophic maxilla by means of implant-supported
      prostheses cannot always be achieved with fixed prostheses because of anatomic,
      esthetic, or economic issues, so for some patients the treatment of choice is a
      removable prosthesis. This article analyzes a new design for implant-supported
      overdentures with horizontal or faciolingual insertion. Its retention system is
      based on frictional forces or stepped interlocking horizontal surfaces and is
      appropriate for patients with skeletal Class II or III relationships with severe
      maxillary atrophies. The design facilitates implant-prosthetic hygiene and
      improved esthetics in patients with nonparallel implants by hiding abutment
      screws. 

PMID- 24079558
TI  - An in vitro comparison of photogrammetric and conventional complete-arch implant
      impression techniques.
AB  - STATEMENT OF PROBLEM: Conventional impression techniques for recording the
      location and orientation of implant-supported, complete-arch prostheses are time
      consuming and prone to error. The direct optical recording of the location and
      orientation of implants, without the need for intermediate transfer steps, could
      reduce or eliminate those disadvantages. PURPOSE: The objective of this study was
      to assess the feasibility of using a photogrammetric technique to record the
      location and orientation of multiple implants and to compare the results with
      those of a conventional complete-arch impression technique. MATERIAL AND METHODS:
      A stone cast of an edentulous mandibular arch containing 5 implant analogs was
      fabricated to create a master model. The 3-dimensional (3D) spatial orientations
      of implant analogs on the master model were measured with a coordinate measuring
      machine (CMM) (control). Five definitive casts were made from the master model
      with a splinted impression technique. The positions of the implant analogs on the
      5 casts were measured with a NobelProcera scanner (conventional method).
      Prototype optical targets were attached to the master model implant analogs, and
      5 sets of images were recorded with a digital camera and a standardized image
      capture protocol. Dimensional data were imported into commercially available
      photogrammetry software (photogrammetric method). The precision and accuracy of
      the 2 methods were compared with a 2-sample t test (alpha=.05) and a 95%
      confidence interval. RESULTS: The location precision (standard error of
      measurement) for CMM was 3.9 um (95% CI 2.7 to 7.1), for photogrammetry, 5.6 um
      (95% CI 3.4 to 16.1), and for the conventional method, 17.2 um (95% CI 10.3 to
      49.4). The average measurement error was 26.2 um (95% CI 15.9 to 36.6) for the
      conventional method and 28.8 um (95% CI 24.8 to 32.9) for the photogrammetric
      method. The overall measurement accuracy was not significantly different when
      comparing the conventional to the photogrammetric method (mean difference = -2.6
      um, 95% CI -12.8 to 7.6). CONCLUSIONS: The precision of the photogrammetric
      method was similar to CMM, but lower for the conventional method as compared to
      CMM and the photogrammetric method. However, the overall measurement accuracy of
      the photogrammetric and conventional methods was similar.

PMID- 24079559
TI  - Selection patterns of dietary foods in edentulous participants rehabilitated with
      maxillary complete dentures opposed by mandibular implant-supported prostheses: a
      multicenter longitudinal assessment.
AB  - STATEMENT OF PROBLEM: Documentation of long-term changes in food intake is
      lacking for those treated with a maxillary complete denture opposed by a
      mandibular, screw-retained, implant-supported fixed prosthesis. PURPOSE: The
      purpose of this study was to evaluate the selection patterns of dietary foods
      over 5 years for edentulous participants treated in a multicenter prospective
      clinical trial that compared cast alloy versus laser-welded titanium frameworks
      of an implant-supported prostheses opposed by maxillary complete dentures to
      rehabilitate edentulous participants. MATERIAL AND METHODS: The study assessed
      data from a multicenter prospective clinical trial that followed edentulous
      participants from an initial baseline of wearing existing complete dentures to
      implant placement, restoration with a mandibular implant-supported prosthesis
      opposed by a maxillary complete denture, to follow-up assessment of these
      treatments over 5 years. The 32 participants in the cohort were treated at 5 of 9
      participating centers. The data collected included 2 dietary forms, a
      standardized 4-day food diary form, and a dietary habits questionnaire. Each
      participant completed forms before entering into treatment (control) and at the 1
      and 5-year follow-up assessment after being treated with a maxillary complete
      denture opposing a mandibular complete-arch fixed implant-supported prosthesis.
      Descriptive statistics were calculated for each measure at each assessment point.
      Regression analysis and the Sign test were used to calculate change in the
      participants' nutritional status (alpha=.05). RESULTS: Among the findings, it was
      noted that difficulty in masticating hard, raw, and fibrous foods decreased and
      intake of vegetable portions increased significantly from 2.5 to 3.3 servings.
      Participant comfort in eating in public places and their enjoyment of eating were
      significantly improved from 50% of participants being uncomfortable with their
      prior complete denture treatment to only 4% after 5 years. CONCLUSIONS: Within
      the limitations of this study, it was concluded that vegetable intake and ability
      to masticate raw, hard, and fibrous food for these participants improved when
      they received a mandibular implant-supported prosthesis opposed by a maxillary
      complete denture. According to the analysis and findings, the overall eating
      experience was more pleasurable, and eating in public was more comfortable after
      replacement of complete dentures with a mandibular implant-supported prosthesis.

PMID- 24079560
TI  - Customized anterior guidance for occlusal devices: classification and rationale.
AB  - Occlusal devices can protect the dentition from attrition and are commonly
      prescribed for the treatment of myogenous orofacial pain. The occlusal scheme of
      the device controls the forces on teeth during mandibular closure and excursions.
      Smooth anterior guidance from anterior teeth contact and posterior teeth
      disclusion has been described as a component of a therapeutic occlusion. Clinical
      research on the effects of occlusal devices is extensive, but documentation about
      the actual occlusion studied is lacking. A classification of anterior guidance
      design for occlusal devices and the rationale for optimum force distribution is
      presented. This classification can guide clinicians as to the criteria for proper
      occlusal device fabrication and improve dental research.

PMID- 24079562
TI  - Fracture strength and microstructure of Y-TZP zirconia after different surface
      treatments.
AB  - STATEMENT OF PROBLEM: Airborne-particle abrasion of the inner and outer surfaces
      of an yttria-stabilized tetragonal zirconia polycrystal (Y-TZP) core is used in
      an attempt to enhance the bond strength between the core and the veneering
      porcelain and to increase the surface area for cementation. However, airborne
      particle abrasion introduces surface flaws that act as stress concentrators that
      may compromise the mechanical strength of the ceramic. PURPOSE: The purpose of
      this study was to investigate the effect of airborne-particle abrasion and heat
      treatment on the microstructure, biaxial flexural strength, and reliability of Y
      TZP zirconia ceramics before veneering and cementation. MATERIAL AND METHODS:
      Forty-eight disks (15 mm in diameter, 0.5 mm in thickness) of Y-TZP were divided
      into 6 groups. Three treatments (untreated, airborne-particle abrasion, and heat
      treatment after airborne-particle abrasion) were applied to the upper surfaces,
      and 2 treatments (untreated and airborne-particle abrasion) were applied to the
      lower surfaces to mimic the preparation for veneering and cementation. For
      airborne-particle abrasion, 110 MUm Al2O3 particles were used. The maximum load
      at fracture was calculated with a biaxial flexural strength test. The upper
      surfaces were facing the loading piston, and the lower surfaces were facing the
      supporting jig during testing. Results were analyzed with 2-way ANOVA
      (alpha=.05). The treated and fractured surfaces were observed with a scanning
      electron microscope. The relative content of the monoclinic phase was quantified
      with an x-ray diffraction analysis. RESULTS: The group with airborne-particle
      abraded lower surfaces showed significantly higher flexural strength than the
      untreated group (P<.001). The SEM images of the airborne-particle abraded
      zirconia specimens showed rough and irregular surfaces. The fracture initiated
      from the tension side, which was opposite to the applied load. CONCLUSIONS:
      Within the limits of this in vitro study, the results showed that airborne
      particle abrasion of the lower surfaces increases the flexural strength of Y-TZP
      zirconia.

PMID- 24079561
TI  - Influence of preparation design and ceramic thicknesses on fracture resistance
      and failure modes of premolar partial coverage restorations.
AB  - STATEMENT OF PROBLEM: Preparation designs and ceramic thicknesses are key factors
      for the long-term success of minimally invasive premolar partial coverage
      restorations. However, only limited information is presently available on this
      topic. PURPOSE: The purpose of this in vitro study was to evaluate the fracture
      resistance and failure modes of ceramic premolar partial coverage restorations
      with different preparation designs and ceramic thicknesses. MATERIAL AND METHODS:
      Caries-free human premolars (n=144) were divided into 9 groups. Palatal onlay
      preparation comprised reduction of the palatal cusp by 2 mm (Palatal Onlay
      Standard), 1 mm (Palatal-Onlay-Thin), or 0.5 mm (Palatal Onlay Ultrathin).
      Complete-coverage onlay preparation additionally included the buccal cusp
      (Occlusal Onlay Standard; Occlusal Onlay Thin; Occlusal Onlay Ultrathin). Labial
      surface preparations with chamfer reductions of 0.8 mm (Complete-Veneer
      Standard), 0.6 mm (Complete-Veneer-Thin), and 0.4 mm (Complete Veneer Ultrathin)
      were implemented for complete veneer restorations. Restorations were fabricated
      from a pressable lithium disilicate ceramic (IPS-e.max-Press) and cemented
      adhesively (Syntac-Classic/Variolink-II). All specimens were subjected to cyclic
      mechanical loading (F=49 N, 1.2 million cycles) and simultaneous thermocycling (5
      degrees C to 55 degrees C) in a mouth-motion simulator. After fatigue,
      restorations were exposed to single-load-to-failure. Two-way ANOVA was used to
      identify statistical differences. Pair-wise differences were calculated and P
      values were adjusted by the Tukey-Kramer method (alpha=.05). RESULTS: All
      specimens survived fatigue. Mean (SD) load to failure values (N) were as follows:
      837 (320/Palatal-Onlay-Standard), 1055 (369/Palatal-Onlay-Thin), 1192
      (342/Palatal-Onlay-Ultrathin), 963 (405/Occlusal-Onlay-Standard), 1108
      (340/Occlusal-Onlay-Thin), 997 (331/Occlusal-Onlay-Ultrathin), 1361 (333/Complete
      Veneer-Standard), 1087 (251/Complete-Veneer-Thin), 883 (311/Complete-Veneer
      Ultrathin). Palatal-onlay restorations revealed a significantly higher fracture
      resistance with ultrathin thicknesses than with standard thicknesses (P=.015).
      Onlay restorations were not affected by thickness variations. Fracture loads of
      standard complete veneers were significantly higher than thin (P=.03) and
      ultrathin (P<.001) restorations. CONCLUSIONS: In this in vitro study, the
      reduction of preparation depth to 1.00 and 0.5 mm did not impair fracture
      resistance of pressable lithium-disilicate ceramic onlay restorations but
      resulted in lower failure loads in complete veneer restorations on premolars.

PMID- 24079563
TI  - Solubility and strength of zirconia-based dental materials after artificial
      aging.
AB  - STATEMENT OF PROBLEM: Advanced high-strength dental ceramics based on zirconium
      oxide are widely used for dental restorations. However, their durability in
      liquids has been questioned. PURPOSE: The purpose of this study was to compare
      the flexure strength of zirconium dioxide materials designed for different
      sintering techniques before and after surface exposure to an acidic solution and
      to correlate the dissolution of the materials with strength data. MATERIAL AND
      METHODS: An accelerated aging test, immersion in hot (80 degrees C) 4 vol% acetic
      acid was used to study the solubility of elements from the surface and the effect
      on the strength of 3 dental zirconia products: DY: Y-TZP material, milled in
      HIPed state (Denzir); DM: Mg-PSZ material, milled in dense-sintered state (Denzir
      M); and CY: Y-TZP material, milled from presintered block and then dense-sintered
      (Cercon base). Disks were prepared with a surface conditioning as for copings
      provided for dental restorations. After immersion for 1 week, the liquid was
      analyzed for a range of elements with ICP-MS. Biaxial flexure strength was
      measured for 3 samples (n=15) of each material: ground on a 20 um diamond disk
      without immersion; after 1 week's immersion in acetic acid; and after 1 week's
      immersion, grinding, and 1 more week in acid. Fracture probability was analyzed
      by maximum likelihood attribution of individual measurements to 1 or 2 Weibull
      distributions, each with 2 free parameters. RESULTS: Dissolution was found to be
      limited. The total mass loss was less than 0.7 ug/cm(2) for Y-TZP and 3.5
      ug/cm(2) for Mg-PSZ. The mean strength was reduced for all materials after
      immersion in the fluid. Weibull statistics revealed 2 fracture mechanisms in Y
      TZP milled in fully sintered condition. For DY only, 2 distributions
      significantly (P>.99) improved the description of individual treatment data.
      CONCLUSIONS: Y-TZP materials showed the highest biaxial flexure strength.
      Immersion for 1 week in hot 4 vol% acetic acid weakened all 3 zirconia materials
      by 100 to 200 MPa. Milling in the presintered state resulted in less variability
      than milling in the HIPed state. Mg-PSZ exhibited the least variability.

PMID- 24079564
TI  - Fracture load of milled polymeric fixed dental prostheses as a function of
      connector cross-sectional areas.
AB  - STATEMENT OF PROBLEM: Polymeric computer-aided design/computer-aided
      manufacturing (CAD/CAM) blocks exhibit various advantages in contrast to
      conventionally processed resin restorations. However, the influence of connector
      dimensions on resin fixed dental prostheses (FDPs) has not yet been investigated.
      PURPOSE: This study evaluated the impact of connector cross-sectional area (CSA)
      on the fracture load of 3-unit CAD/CAM FDPs and compared this with conventionally
      fabricated ones. MATERIAL AND METHODS: Anatomically shaped 3-unit FDPs with the
      CSAs of 6, 9, 12, and 16 mm(2) (N=240, n=15 per material and per CSA) were
      fabricated from the following CAD/CAM materials: artBloc Temp (AT), TelioCAD
      (TC), CAD-Temp (CT), and one conventional resin material, CronMix K (CMK) as the
      control group. The fracture load was tested and the data were analyzed with 2-way
      ANOVA, 1-way ANOVA, the Scheffe post hoc test, and Weibull statistics (alpha=05).
      RESULTS: CMK showed the significant lowest values for all CSAs followed by CT,
      except for the 12 mm(2) connector (P<.001). The CAD/CAM FDPs exhibited a
      significant increase in fracture load with the increase of CSA (P<.001).
      Conventionally fabricated FDPs presented an increase of values up to the CSA of
      12 mm(2). For TC, the shape increased with a larger CSA. The other materials
      exhibited no tendencies in this regard. Among the 12 mm(2) groups, AT exhibited
      the highest shape value (19.1), and among the 16 mm(2) groups, TC showed the
      highest shape value (17.0). The CMK FDPs with a CSA of 16 mm(2) showed almost
      half as high a shape parameter (6.4) than the other three CSAs. CONCLUSIONS:
      CAD/CAM resin FDPs revealed significantly higher fracture load values than
      conventionally fabricated FDPs and showed a significant increase in fracture load
      with the increase of the CSA.

PMID- 24079565
TI  - Effects of interim acrylic resins on the expression of cytokines from epithelial
      cells and on collagen degradation.
AB  - STATEMENT OF PROBLEM: Interim acrylic resins release agents that alter cytokine
      expression in the surrounding tissues, which could alter extracellular matrix
      degradation. PURPOSE: The purpose of the study was to evaluate the responses of
      human epidermal keratinocytes to eluates of interim acrylic resins in regards to
      cytokine expression and cell-mediated collagen degradation. MATERIAL AND METHODS:
      Specimens of 4 different interim acrylic resins (HI-I, Jet Acrylic, SNAP acrylic,
      and Protemp Plus) were placed in Epilife medium for 48 hours and the eluates
      collected. The cells were incubated for 72 hours in nontoxic concentrations of
      the eluates. Cytotoxicity was evaluated with lactate dehydrogenase assays and
      cytokine expression with cytokine antibody arrays. Collagen degradation was
      determined with a collagen type I assay. The experiments were performed 3 times.
      Data were analyzed with 1-way and mixed-model ANOVA (alpha=.05). RESULTS: None of
      the eluates were cytotoxic. Cytokine expression from the heat-activated
      polymethyl methacrylate resin group was significantly less for interleukin-3, but
      significantly greater for interlukin-7. Expression for the chemically activated
      polymethyl methacrylate resin group was significantly less for growth-regulated
      oncogene-alpha, interleukin-1alpha, and interleukin-3. Expression for the
      chemically activated polyethyl methacrylate resin group was significantly less
      for interleukin-1alpha and interleukin-3, but significantly greater for
      interleukin-13 and monocytes chemoattractant protein-3. The cytokine expression
      induced by chemically activated bis-acryl composite resin was significantly
      greater for granulocyte-macrophage colony stimulating factor, interleukin-7, and
      monocytes chemoattractant protein-3, but significantly less for growth-regulated
      oncogene-alpha. Collagen degradation was not significantly different in any of
      the groups. CONCLUSIONS: The eluates used were not cytotoxic and did not induce
      cell-mediated collagen degradation. Some significant changes in cytokine
      expression were noted.

PMID- 24079566
TI  - The effect of type of restoration on the stress field developed in terminal
      abutments with severely reduced periodontal support and coronal structure.
AB  - STATEMENT OF PROBLEM: Periodontally compromised teeth (PCT) that serve as
      terminal abutments (TAs) are often challenging depending on the post-and-core
      treatment, the type of partial fixed dental prosthesis (PFDP), and the
      periodontal support. PURPOSE: The purpose of this study was to investigate the
      biomechanical impact of 3 types of PFDP supported by cast post-and-cores on PCT
      serving as terminal abutments. MATERIAL AND METHODS: A 3-dimensional (3D) model
      of a human mandible was fabricated by using computed tomography (CT) images and
      parameterized in a computer-aided design (CAD) environment as follows: Right
      premolar preparation geometries were designed. The second premolar was assembled
      with 7-mm or 10-mm cast post-and-core models. Both premolar-models were designed
      to support single, splinted, or 1-unit cantilever splinted crowns. In each
      situation, their periodontium geometries were designed to be reduced by 10%, 50%,
      and 70%. All models were imported into a 3D finite element analysis (FEA)
      environment and loaded; von Mises stress values and distribution patterns were
      evaluated. RESULTS: Insertion of the post primarily affected the apical areas of
      both the root and post; the type of PFDP and periodontal support mainly affected
      stress distribution. In patients with a normal periodontium, splinting the teeth
      did not contribute to their stress relief. By extending the post length, a
      stressful area close to the apex of the post was developed. Splinting mitigated
      the stress field of the coronal part of the 50% PCT (up to 98.9%); the 30% PCT
      experienced a substantial decrease (up to 215.9%) in stress in the radical part
      as well. The increase in the length of the post produced negligible stress
      related differences in the apical part of the 50% PCT (0.2% to 2.6%). The use of
      the 7-mm post effectively relieved the radical part of the splinted 30% PCT. The
      magnitude of the stress on the radical part of post-restored PCT was considerably
      increased in the presence of a cantilever. CONCLUSIONS: Splinted crowns supported
      by a 7-mm cast post-and-core are a favorable biomechanical approach for the
      restoration of PCT with severe loss of coronal structure. The use of a cantilever
      greatly aggravates the biomechanical response, especially of post-restored PCT.

PMID- 24079567
TI  - Evaluation of the properties of a tissue conditioner containing origanum oil as
      an antifungal additive.
AB  - STATEMENT OF PROBLEM: Adherence and colonization of Candida albicans on tissue
      conditioners is common and results in irritation of the denture-bearing mucosa.
      PURPOSE: The purpose of this study was to investigate the antifungal activity and
      properties of a tissue conditioner by incorporating origanum oil. MATERIAL AND
      METHODS: Origanum oil at varying concentrations was incorporated into a
      poly(methyl methacrylate) based tissue conditioner (Visco-gel), and its
      antifungal activity against Candida albicans was evaluated at 1 day and 1 week by
      using the agar punch well method. The adherence of Candida albicans, surface
      roughness, tensile strength, and bond strength of the tissue conditioner with an
      optimized origanum oil concentration were evaluated. The data were subjected to 2
      way ANOVA (alpha=.05). RESULTS: Sixty vol% origanum oil in tissue conditioner
      (Visco-gel) showed a mean inhibitory zone of 21.00 +/- 1.58 mm at 1 day and 13.44
      +/- 0.88 mm at 1 week. The control group showed 90 +/- 6.80 yeast cells/mm(2) at
      1 day and 165 +/- 7.63 yeast cells/mm(2) at 1 week, whereas the group with
      origanum oil showed 16 +/- 1.15 yeast cells/mm(2) at 1 day and 32 +/- 4.00 yeast
      cells/mm(2) at 1 week. Surface roughness was less with the incorporation of
      origanum oil. Tensile strength at 1 day was 0.91 +/- 0.52 N for the control
      group, whereas the group with origanum oil showed 0.16 +/- 0.05 N. At 1 day, the
      bond strength of 3.97 +/- 0.75 MPa was observed with control specimens, whereas
      tissue conditioner with origanum oil showed a bond strength of 3.73 +/- 0.65 MPa.
      CONCLUSIONS: Within the limitations of this in vitro study, origanum oil can be
      used as an additive to tissue conditioner to reduce the adherence of Candida
      albicans without significantly affecting its bond strength to heat-polymerized
      acrylic resin.

PMID- 24079568
TI  - Use of thermochromic pigment in maxillofacial silicone elastomer.
AB  - STATEMENT OF PROBLEM: Silicone elastomers are used to fabricate external
      maxillofacial prostheses and are colored to match the adjacent facial skin. In
      cold winter weather, in certain individuals, the color of the skin changes toward
      red, which leads to a color difference between the prostheses and the surrounding
      tissue. PURPOSE: The purpose of this study was to study the use of a
      thermochromic, color-changing pigment in a maxillofacial silicone elastomer to
      mimic the color change of the skin in cold weather. An additional aim was to
      compare different pigment concentrations. MATERIAL AND METHODS: The maxillofacial
      silicone elastomer was colored with an intrinsic coloring technique to match fair
      skin. The skin-colored silicone was divided into 3 groups: fair skin color, fair
      skin color to which was added 0.2 wt% thermochromic pigment, and fair skin color
      with 0.6 wt% thermochromic pigment. Disk-shaped, 7 * 35 mm specimens (n=12 per
      group) were prepared and color measurements were made with a spectrophotometer at
      room temperature and after storage in a freezer. Differences and changes in color
      were calculated according to the CIELAB-system, and changes in the values of the
      L*, a*, and b* color coordinates were analyzed with general linear modeling for
      repeated measures. RESULTS: When the color of the specimens at room temperature
      was compared with the color after storage in a freezer, the color change of both
      thermochromic pigment groups was statistically significant (P<.001) for L * and
      a* values and for b* values in the 0.6 wt% group. The color change of the control
      group (DeltaE 0.95) was not visually noticeable. The change toward redness after
      freezer storage appeared natural in the specimens with 0.2 wt% thermochromic
      pigment (DeltaE 2.66). The color change of the specimens with 0.6 wt%
      thermochromic pigment was too noticeable for clinical use (DeltaE 16.81).
      CONCLUSIONS: A concentration of 0.2 wt% thermochromic pigment led to a slight
      visual color change toward red of the silicone elastomer after freezer storage,
      while a concentration of 0.6 wt% thermochromic pigment led to a more noticeable
      color change.

PMID- 24079569
TI  - Lightweight acrylic resin facial prosthesis for maxillofacial defects: a
      fabrication and retention method.
AB  - Extraoral maxillofacial rehabilitation for compromised or lost facial anatomy
      resulting from the surgical eradication of malignancy, trauma, or congenital
      anomalies is commonly accomplished with a silicone prosthesis. However, with
      increasing size and weight, a silicone prosthesis can lose retention. This report
      presents 2 patient treatments to introduce a fabrication and retention method for
      a lightweight acrylic resin facial prosthesis. The prosthesis was fabricated by
      bonding an acrylic resin facial shell to a computer-edited facial image printed
      with iron-on transfers. The completed prosthesis was attached to the skin with
      medical-grade double-sided adhesive tape, which maintained a tight marginal seal
      even when in contact with saliva and water. The strong prosthetic retention of
      the lightweight prosthesis enabled orofacial and speech rehabilitation, which
      makes it a promising alternative to the conventional silicone prosthesis,
      especially for the restoration of extensive maxillofacial defects. 

PMID- 24079570
TI  - A technique to restore worn denture teeth on a partial removable dental
      prosthesis by using ceramic onlays with CAD/CAM technology.

PMID- 24079571
TI  - A magnetic device for recording and reproducing the path of placement for partial
      removable dental prostheses.

PMID- 24079572
TI  - Age-associated changes of walking parameters in Japanese adult women.
AB  - The purpose of this paper is to clarify the age-associated changes in walking
      movements. A two-dimensional movement analysis was conducted on a sample of 177
      healthy women aged 19-82 years, with performance descriptors, kinematics, and
      kinetics as the parameters. An analysis of co-variance, with the gait velocity as
      co-variate and the categorized age group as a fixed factor, was adopted to
      examine the differences in each parameter among eight age groups. We conclude
      that age-associated changes in walking movement occur due to the essential effect
      of aging in walking, rather than due to differences in the physique or decrease
      of the gait velocity.

PMID- 24079573
TI  - Toxicity and pharmacokinetics of nanobiomaterials.

PMID- 24079574
TI  - An overview on pharmacokinetics, disposition, and safety of nanoparticles in
      ocular applications.
AB  - In the past three decades, the application of nanotechnology in ophthalmology has
      gained considerable progress for the treatment of ocular diseases including
      anterior and posterior diseases. Results strongly suggest that delivery of ocular
      medicines, especially those based on macromolecular agents such as proteins,
      peptides, and nucleotides, are greatly enhanced by the use of nanotechnology.
      Generally, ophthalmic drugs are delivered to ocular tissues by precorneal
      instillation and intravitreal injections. An ideal ocular drug delivery system
      should have certain desirable properties, such as excellent corneal and
      conjunctival penetration, prolonged residence time, sustained release, and easy
      administration. It should also be nonirritating and noncytotoxic. This review
      places in perspective the importance of nanoparticles in the pharmacokinetics and
      disposition of ocularly administered drugs. Furthermore, the safety and
      compatibility of nanoparticles for ocular administration are specifically
      discussed. 

PMID- 24079575
TI  - Heterogeneous uptake and adsorption of gas-phase formic acid on oxide and clay
      particle surfaces: the roles of surface hydroxyl groups and adsorbed water in
      formic acid adsorption and the impact of formic acid adsorption on water uptake.
AB  - Organic acids in the atmosphere are ubiquitous and are often correlated with
      mineral dust aerosol. Heterogeneous chemistry and the uptake of organic acids on
      mineral dust particles can potentially alter the properties of the particle. In
      this study, heterogeneous uptake and reaction of formic acid, HCOOH, the most
      abundant carboxylic acid present in the atmosphere, on oxide and clays of the
      most abundant elements, Si and Al, present in the Earth's crust are investigated
      under dry and humid conditions. In particular, quantitative adsorption
      measurements using a Quartz Crystal Microbalance (QCM) coupled with spectroscopic
      studies using Attenuated Total Reflection Fourier Transform Infrared (ATR-FTIR)
      spectroscopy are combined to allow for both quantification of the amount of
      uptake and identification of distinct adsorbed species formed on silica, alumina,
      and kaolinite particle surfaces at 298 K. These oxides and clay particles show
      significant differences in the extent and speciation of adsorbed HCOOH due to
      inherent differences in surface -OH group reactivity. Adsorbed water, controlled
      by relative humidity, can increase the irreversible uptake of formic acid.
      Interestingly, the resulting layer of adsorbed formate on the particle surface
      decreases the particle hydrophilicity thereby decreasing the amount of water
      taken up by the surface as measured by QCM. Atmospheric implications of this
      study are discussed. 

PMID- 24079576
TI  - Micellar liquid chromatographic method for the simultaneous determination of
      Levofloxacin and Ambroxol in combined tablets: Application to biological fluids.
AB  - BACKGROUND: Levofloxacin hemihydrate (LEV) and ambroxol HCl (AMB) are available
      for the treatment of upper and lower respiratory tract infections. A survey of
      the literature reveals that two reversed phase HPLC methods were e reported for
      the simultaneous determination of LEV and AMB in pharmaceutical preparations.
      However the reported methods suffers from the low sensitivity, no application of
      the method in the combined tablets and no application to biological fluids. Also
      the toxic effects of the used solvents which are harmful to human beings. For
      this reason, our target was to develop a simple sensitive, less hazardous
      micellar HPLC method for the simultaneous determination of LEV and AMB in their
      combined dosage forms and plasma. RESULTS: The method showed good linearity over
      the ranges of 1-44 MUg/mL and 1-20 MUg/mL with limits of detection 0.26 and 0.07
      MUg/mL and limits of quantification 0.80 and 0.20 MUg/mL for LEV and AMB,
      respectively. The method was further extended to the determination of LEV in
      spiked human plasma with mean percentage recoveries of 100.10% +/- 1.14 as well
      as determination of LEV in real human plasma without prior extraction.
      Statistical evaluation of the data was performed according to ICH Guidelines.
      CONCLUSION: The suggested method was successfully applied for the simultaneous
      analysis of the studied drugs in their co-formulated tablets and human plasma.
      The mean percentage recoveries in combined tablets were 100.20 +/- 1.64 and
      100.72 +/- 1.11 for LEV and AMB, respectively and 100.10 +/- 1.14 for LEV in
      spiked human plasma. Statistical comparison of the results with those of the
      comparison method revealed good agreement and proved that there were no
      significant difference in the accuracy and precision between the two methods
      respectively.

PMID- 24079577
TI  - Understanding treatment decision making in juvenile idiopathic arthritis: a
      qualitative assessment.
AB  - BACKGROUND: The increase in therapeutic options for juvenile idiopathic arthritis
      (JIA) has added complexity to treatment decisions. Shared decision making has the
      potential to help providers and families work together to choose the best
      possible option for each patient from the array of choices. As part of a needs
      assessment, prior to design and implementation of shared decision making
      interventions, we conducted a qualitative assessment of clinicians' current
      approaches to treatment decision making in JIA. METHODS: Pediatric rheumatology
      clinicians were recruited from 2 academic children's hospitals affiliated with a
      quality improvement learning network, using purposive and snowball sampling. Semi
      structured interviews elicited how clinicians with prescribing authority (n = 10)
      interact with families to make treatment decisions. Interviews were audio
      recorded and transcribed verbatim. A multi-disciplinary research team used
      content analysis to analyze the interview data.To validate data from individual
      interviews and enrich our understanding, we presented the interview results to
      pediatric rheumatology clinicians attending a learning network meeting (n = 24
      from 12 children's hospitals). We then asked the clinicians questions to further
      identify and discuss areas of variation in the decision-making processes.
      RESULTS: Clinicians described a decision-making process in which they, rather
      than the family or other care team members, consistently initiated treatment
      decisions. Initial treatment options presented to families generally reflected
      the clinician's preferred treatment approaches, which differed across clinicians.
      Clinicians used various methods to inform families about treatment options and
      tailor information according to perceptions of a family's information needs,
      level of comprehension or mood (e.g. anxiety). The attributes of medication
      presented to families fell into 4 categories: benefits, risks, logistics and
      family preferences. Clinicians typically included family members in the decision
      to initiate JIA treatment after limiting the options to fit the clinical
      situation and the clinician's own preferences. Family members' preferences were
      seen as more integral in the decision to stop treatment after symptom remission.
      CONCLUSIONS: Decision making about initial JIA treatment appears to be largely
      driven by clinician preferences. Family preferences are more likely to be
      considered for treatment discontinuation. Opportunities exist to develop, test,
      and implement tools to facilitate shared decision making in pediatric
      rheumatology.

PMID- 24079578
TI  - Nails and the clinician.

PMID- 24079579
TI  - Nail anatomy.
AB  - The nail unit comprises the nail plate, the surrounding soft tissues, and their
      vasculature and innervation based upon the distal phalanx. The nail plate is a
      laminated keratinized structure lying on the nail matrix (15-25%), the nail bed
      with its distal onychodermal band (75-85%), and the hyponychium at its free edge.
      The distal part of the matrix, the lunula characterized by its half-moon shape,
      can be observed in some digits. The nail plate is embedded by the proximal and
      lateral folds. From the proximal nail fold, the cuticle (also known as the
      eponychium), adheres to the superficial surface of the proximal nail plate. The
      nail unit possesses a complex and abundant vascular network to ensure adequate
      blood supply. Finally, both the periungual soft tissues and the nail folds are
      innervated. The shapes, structure, and inter-relationships of these tissues are
      factors in the way nails present with disease and how we understand and manage
      those diseases. In particular, an understanding of the surgical anatomy is
      important for those undertaking diagnostic or curative operations on the nail.
      With this knowledge, the most appropriate surgery can be planned and the patient
      can be provided with accurate and clear guidance to enable informed consent. 

PMID- 24079580
TI  - Nail surgery.
AB  - Nail surgery is a special branch of hand and dermatologic surgery. It is not
      widely performed, and many physicians do not feel at ease to perform it. The
      objective of this contribution is to give a short overview of the most important
      surgical procedures in clinical practice. References from the literature and the
      author's own experiences are condensed to describe what a dermatologic
      practitioner with knowledge of the nail and some surgical skills can perform.
      Nail surgery is a precise technique that requires careful administration and
      attention to details. Proper patient preparation starts with a patient history to
      identify potential contraindications and to prevent unnecessary complications.
      The author recommends isopropyl alcohol scrub and chlorhexidine for disinfection
      and ropivacaine 1% for anesthesia. The technique used for anesthesia depends on
      the type of surgery. Surgical procedures are described for diagnostic biopsies,
      nail avulsion in general, onychogryposis, paronychia treatment, hematomas and
      bone fracture due to trauma, removal of subungual foreign bodies, ingrowing
      nails, pincer nails, warts, ungual fibrokeratomas, digital myxoid pseudocyst,
      subungual exostoses, and various tumors. If performed correctly with adequate
      skills, nail surgery will lead to functionally and aesthetically satisfying
      results in the majority of instances. 

PMID- 24079581
TI  - Nail pathology.
AB  - When dealing with nails, pathologic examination is often indispensable to reach
      an accurate diagnosis. This requires a biopsy correctly performed by the
      dermatologist, a specimen correctly handled in the pathology lab, and a
      pathologist with good knowledge of the various nail conditions. The normal nail
      histology is first described in this paper. The pathologic aspects of melanocytic
      lesions, nonmelanocytic tumors of the nail apparatus, inflammatory nail
      conditions, and onychomycosis are then considered, together with their main
      differential diagnoses. 

PMID- 24079582
TI  - Diagnosing onychomycosis.
AB  - The diagnosis of onychomycosis may require the use of mycological diagnostic
      testing to supplement the clinical presentation. In order to verify that
      onychomycosis is present, the viability, penetrance, and species of the fungal
      infection should be determined. The most common diagnostic tests are mycological
      culture, direct microscopic examination, histopathologic study, and polymerase
      chain reaction (PCR)-based tests. Each of these tests has individual strengths in
      satisfying the three criteria, with a minimum of two positive diagnostic tests
      being the gold standard for confirming all three diagnostic criteria. 

PMID- 24079583
TI  - Therapies for the treatment of onychomycosis.
AB  - Onychomycosis treatments include nail avulsion and debridement by chemical or
      surgical procedures, topical and oral antifungals, and device-based therapies.
      The advantages, disadvantages, and limitations of the different types of
      treatments--including the most commonly prescribed topical (ciclopirox) and oral
      (terbinafine, itraconazole, and fluconazole) treatments for onychomycosis caused
      by dermatophytes, non-dermatophyte molds, and yeasts--are reviewed. Safety and
      efficacy data for the healthy adult population and for special populations such
      as children and diabetic patients have confirmed the importance of proper
      mycological diagnosis before the initiation of therapy as well as the evaluation
      of the risks and benefits of the different treatments.

PMID- 24079584
TI  - Improved efficacy in onychomycosis therapy.
AB  - The success rate of onychomycosis treatment is limited by several factors,
      including the access of the therapeutic agent to the fungal mass, the presence of
      conidia, and the susceptibility of the different infectious agents to the
      antifungals. Different strategies used to improve efficacy of the currently
      available antifungal treatments, their rationale, and the published evidence of
      their beneficial effects are reviewed. An improved efficacy was demonstrated for
      some of these strategies, such as combined oral and topical antifungal therapies,
      whereas most of them lack clear and direct evidence of an increase in therapeutic
      success. 

PMID- 24079585
TI  - Pediatric nail conditions.
AB  - Pediatric nail findings are plentiful and can range from benign processes to the
      initial signs of a systemic condition. The examination of the nail is an
      essential part of the pediatric physical examination. The nail unit consists of
      the nail plate, the nail matrix, the hyponychium, the nail bed, and the
      surrounding nail folds. Conditions that affect the nail unit have a variety of
      etiologies; these include inflammatory, congenital, and hereditary conditions as
      well as tumors and trauma. This review describes many of the nail conditions that
      are seen in the pediatric population. 

PMID- 24079586
TI  - Cosmetic treatment of nails.
AB  - Nail cosmetics are an important part of personal expression. Although their use
      can result in a variety of dermatologic issues, the popularity of nail cosmetics
      is huge. Dermatologists must recognize problems associated with nail cosmetics
      and understand the process for using these cosmetics. Many problems can be
      avoided through careful use or a change in the application procedure. 

PMID- 24079587
TI  - Common nail disorders.
AB  - Brittle nail, simple chronic paronychia, and onycholysis represent three of the
      most prevalent nail disorders. Brittle nails are characterized by increased
      fragility of the nail plate due to damage to the nail matrix or changes to nail
      plate cohesion, caused by internal and/or external factors. Simple chronic
      paronychia represents an inflammatory process of the lateral and/or proximal nail
      folds of the fingernails or toenails often preceded by damage to the cuticle.
      Onycholysis describes the detachment of the nail plate from its nail bed, often
      attributable to dermatologic conditions, infections, drug therapy, or trauma. 

PMID- 24079588
TI  - Onychoscopy.
AB  - Dermatoscopy can be used to evaluate the nail apparatus (ie, onychoscopy), and it
      is helpful for the diagnosis of numerous nail diseases and tumors. This article
      reviews the information that can be obtained in cases of nail dyschromia and
      especially in cases of melanonychia, in which the distinction between benign
      melanocytic activation or proliferation and malignancy is crucial. Dermatoscopic
      changes that accompany specific nail diseases are also reviewed, such as those
      observed with subungual hemorrhage, bacterial and fungal nail infections,
      psoriasis of the nail, lichen planus of the nail, and vascular abnormalities of
      the nail fold. 

PMID- 24079589
TI  - Longitudinal melanonychias.
AB  - Melanonychia is black or brown pigmentation that appears in the fingernails and
      toenails. The pigment can come from exogenous sources, such as bacteria or fungal
      infection, tar, or blood. Endogenous causes include aberrant melanin production
      in the nail bed, resulting in a longitudinal presentation. Melanonychia can
      indicate the presence of cancerous growths, as well as infection. Diagnostic
      measures, including dermatoscopy, biopsy, and histopathology, can determine the
      cause and direct the course of treatment. Malignant lesions should be excised,
      and underlying infections should be addressed with antibiotics or antifungals.
      Benign lesions and hyperpigmentation may benefit from a wait-and-see approach. 

PMID- 24079590
TI  - Nail tumors.
AB  - Most neoplasms of the nail apparatus have different clinical appearances,
      courses, and biological behaviors as compared with similar tumors located
      elsewhere on the skin. Some of these tumors are unique to the nail, such as
      onychomatricoma. As a general rule, benign lesions respect the general
      architecture of the nail apparatus, whereas malignant ones are destructive. Our
      review covers the most common nail tumors, from benign ones to the most frequent
      nail malignancy, the squamous cell carcinoma, which actually is the greatest
      simulator. We will also discuss new approaches to the diagnosis and treatment of
      melanoma of the nail apparatus. Physicians should be aware of these conditions
      and their management. 

PMID- 24079591
TI  - Drug-related nail disease.
AB  - Drug-induced nail abnormalities can present with a wide variety of clinical
      manifestations that are often dose-related and that disappear after drug
      withdrawal. Some nail changes are asymptomatic and only cause cosmetic problems,
      whereas others cause pain and discomfort and impair manual activities or
      deambulation. New side effects have been recently observed with different groups
      of anticancer agents. These include painful onycholysis and subungual abscesses
      caused by taxanes and anthracyclines (eg, doxorubicin) in addition to ingrown
      nails, paronychia, and pyogenic granuloma associated with the use of tyrosine
      kinase inhibitors of the epidermal growth factor receptor (eg, erlotinib,
      gefitinib). 

PMID- 24079592
TI  - Nail abnormalities associated with systemic pathologies.
AB  - Nail abnormalities can arise in conjunction with or as a result of systematic
      pathologies. These pathologies include single-organ diseases, multisystemic
      diseases, and drug-induced insults. Clinical signs associated with these
      conditions include dyschromias, vascular alterations, periungual tissue changes,
      textural dystrophies, contour alterations, and growth-rate alterations. The
      associated systemic pathologies may affect any part of the nail apparatus,
      including the nail matrix, the nail plate, the nail bed, the underlying
      vasculature, and the periungual tissues. The anatomical location and extent of
      damage determine the clinically manifested anomaly. 

PMID- 24079593
TI  - The Karabus affair will be repeated in the future for others going to practice in
      the United Arab Emirates.

PMID- 24079594
TI  - Medical student Dermatology Interest Groups.
AB  - The Dermatology Interest Group (DIG) at the University of Texas Medical Branch
      (UTMB) blog (digutmb.blogspot.com) was created in 2004 with the aims of
      increasing communication and collaboration among students, faculty, residents,
      and alumni, promoting educational opportunities, and fostering the missions for
      which DIG was created. This blog is unique, because its frequent activity is
      directed toward the educational and professional needs of medical students and
      residents. We assessed the use of this blog by evaluating the number of blog
      views and audience members with relationship to the number of posts and post
      content over time via a tracking system. We found that there has been an increase
      in blog posts, views, and subscribers, as well as in areas of post content
      including dermatology resources/news/articles, residency applications, and
      resident-related information. Usefulness of such posts expands beyond UTMB
      students, which increases blog views and widens viewer audience. An international
      viewer population also was evaluated. Recorded blog viewing time was 1 minute, 57
      seconds, which is more time than needed to read a post, suggesting use of
      additional blog information. This review of the DIG at the UTMB blog demonstrates
      how the use of web-based tools, in addition to the inherent benefits of medical
      student interests groups, are valuable resources for students, residents, and
      faculty. 

PMID- 24079599
TI  - Postclustering dynamic covalent modification for chirality control and chiral
      sensing.
AB  - Cluster-based functional materials are appealing, because clusters are well
      defined building units that can be rationally incorporated for the tuning of
      structures and properties. Postclustering modification (PCM) allows for tailoring
      properties through the structural modification of a cluster with preorganized
      funtional groups. By introducing aldehydes into a robust gold-silver cluster via
      a protection-deprotection process, we manage to synthesize a new cluster bearing
      six reactive sites, which are available for PCM through dynamic covalent imine
      bonds formation with chiral monoamines. Chirality is transferred from the amine
      to the gold-silver cluster. The homochirality of the resulted cluster has been
      confirmed by X-ray structural determination and CD spetroscopy. Intense CD
      signals make it practical for chiral recognition and ee value determination of
      chiral monoamines. The strategy of prefunctionalizing of cluster and the concept
      of PCM open a broader prospect for cluster design and applications. 

PMID- 24079595
TI  - The expression of diacylglycerol kinase theta during the organogenesis of mouse
      embryos.
AB  - BACKGROUND: Diacylglycerol kinase (DGK) is a key enzyme that regulates
      diacylglycerol (DG) turnover and is involved in a variety of physiological
      functions. The isoform DGKtheta has a unique domain structure and is the sole
      member of type V DGK. To reveal the spatial and temporal expression of DGKtheta
      we performed immunohistochemical staining on paraffin sections of mouse embryos.
      RESULTS: At an early stage of development (E10.5 and 11.5), the expression of
      DGKtheta was prominently detected in the brain, spinal cord, dorsal root
      ganglion, and limb bud, and was also moderately detected in the bulbus cordis and
      the primordium of the liver and gut. At later stages (E12.5 and 14.5), DGKtheta
      expression persisted or increased in the neocortex, epithalamus, hypothalamus,
      medulla oblongata, and pons. DGKtheta was also evident in the epidermis, and
      nearly all epithelia of the oropharyngeal membrane, digestive tract, and
      bronchea. At prenatal developmental stages (E16.5 and E18.5), the expression
      pattern of DGKtheta was maintained in the central nervous system, intestine, and
      kidney, but was attenuated in the differentiated epidermis. CONCLUSION: These
      results suggest that DGKtheta may play important physiological roles not only in
      the brain, but also in diverse organs and tissues during the embryonic stages.

PMID- 24079600
TI  - The pharmacokinetic evaluation of boceprevir for treatment of hepatitis C virus.
AB  - INTRODUCTION: Boceprevir is an NS3/NS4A serine protease inhibitor that was
      approved for use in Hepatitis C virus (HCV) genotype 1 patients by the US Food
      and Drug Administration (FDA) in May 2011. The approval of this protease
      inhibitor marked a major paradigm shift in the treatment of HCV, as it was one of
      the first of many new small molecules specifically designed and approved for HCV.
      AREAS COVERED: In this article, the authors summarize boceprevir's
      pharmacokinetic and pharmacodynamic properties. In addition, they review Phase II
      and III trials of boceprevir as well as its clinical efficacy, dosing and safety.
      EXPERT OPINION: Boceprevir is a potent protease inhibitor for the treatment of
      genotype 1 HCV. It has a well-tolerated side-effect profile and increases the
      likelihood of SVR in naive and previously treated patients. The impending release
      of newer more efficacious direct-acting antivirals may limit the use of
      boceprevir for patients infected with HCV.

PMID- 24079601
TI  - Interplay between different magnetisms in Cr-doped topological insulators.
AB  - Breaking the time-reversal-symmetry of topological insulators through magnetic
      doping has led to exotic physical discoveries. Here, we report the gate-dependent
      magneto-transport measurements on the Cr-doped (BixSb1-x)2Te3 thin films. With
      effective top-gate modulations, we demonstrate the presence of both the hole
      mediated RKKY coupling and carrier-independent van Vleck magnetism in the
      magnetic TI systems. Most importantly, by varying the Cr doping concentrations
      from 2% to 20%, we unveil the interplay between the two magnetic orders and
      establish the valid approach to either enhance or suppress each individual
      contribution. The electric-field-controlled ferromagnetisms identified in the Cr
      doped TI materials will serve as the fundamental step to further explore the TRS
      breaking TI systems, and it may also help to expand the functionality of TI-based
      device for spintronics applications. 

PMID- 24079602
TI  - Synthesis of triazolo isoquinolines and isochromenes from 2-alkynylbenzaldehyde
      via domino reactions under transition-metal-free conditions.
AB  - We describe two simple straightforward syntheses of triazolo isoquinolines (3)
      and isochromenes (7) from 2-alkynylbenzaldehydes (1) as a common synthon. The
      synthetic strategy for 3 involves formation of the (E)-1-(2-nitrovinyl)-2
      (alkynyl)benzene species 2 via condensation of synthon 1 with nitromethane
      followed by a [3 + 2] cycloaddition/extrusion of the nitro group/regioselective 6
      endo cyclization domino sequence. In yet another strategy, the synthon 1 was
      condensed with nitromethane followed by electrophilic iodo cyclization of the
      resulting 2-nitro-1-(2-(alkynyl)phenyl)ethanol (6) to furnish iodo isochromene
      derivatives. The salient feature of the above two strategies involves formation
      of the corresponding heterocycles under metal-free conditions in good yields. 

PMID- 24079603
TI  - Comparison of the new Mycofast Revolution assay with a molecular assay for the
      detection of genital mycoplasmas from clinical specimens.
AB  - BACKGROUND: Genital mycoplasmas are opportunistic bacteria that are associated
      with undesirable gynaecologic and reproductive events. Mycoplasmas are fastidious
      bacteria with increasing resistance to routine antimicrobials and often fail to
      grow on conventional culture methods. The commercial Mycofast Revolution assay
      permits the phenotypic detection and identification of genital mycoplasmas.
      Antimicrobial susceptibility testing against five antimicrobial agents with MICs
      corresponding to the CLSI guidelines can also be performed. This study aimed to
      compare the new commercially available Mycofast Revolution assay with a multiplex
      PCR assay. METHODS: Self-collected swabs were obtained from pregnant women
      attending the antenatal clinic of a tertiary academic hospital in Pretoria, South
      Africa from October 2012 to November 2012. These swabs were used to seed UMMt and
      modified Amies transport media. The seeded UMMt transported medium was used to
      inoculate the Mycofast Revolution assay for the identification, enumeration and
      antimicrobial susceptibility testing of genital mycoplasmas. Following DNA
      extraction from the modified Amies transport medium, specimens were subjected to
      a multiplex PCR assay for the detection of genital mycoplasmas. RESULTS: The
      Mycofast Revolution kit had a sensitivity and specificity of 77.3% (95% CI:
      62.15% to 88.51%) and 80% (95% CI: 28.81% to 96.70%), respectively, against the
      PCR assay. The positive and negative predictive values were 97.1% (95% CI: 85.03%
      to 99.52%) and 28.6% (95% CI: 8.57% to 58.08%). Genital mycoplasmas were detected
      in 71.4% (35/49) of samples with the Mycofast Revolution assay with 49% (24/49)
      being Ureaplasma spp. and 22.4% (11/49) mixed strains. The multiplex PCR assay
      had a positivity rate of 89.8% (44/49) for genital mycoplasmas; mixed strains
      were present in 51% (25/49) of samples, Ureaplasma spp. in 16.3% (8/49) and M.
      hominis in 22.4% (11/49) of samples. CONCLUSIONS: There was a fair agreement
      (kappa = 0.319) between the Mycofast Revolution assay and the mPCR assay. With
      the high prevalence rates of genital mycoplasmas, fast and efficient diagnostic
      methods are imperative to treat infections and minimise complications. The
      Mycofast Revolution assay is simple to use, has a short turn-around time and
      interpretation of results are straightforward. This assay circumvents common
      problems experienced with conventional culture and molecular methods in
      diagnostic laboratories where skilled personnel are limited and can be used as an
      alternative diagnostic assay.

PMID- 24079604
TI  - Synthesis of P-triazole dithienophospholes and a cyclodextrin-based sensor via
      click chemistry.
AB  - The synthesis of a series of highly luminescent, functional dithienophospholes
      via a click reaction is reported. Slight modification of the lateral aromatic
      substituents leads to a significant difference in their solid-state organization.
      In addition, a novel water-soluble beta-cyclodextrin hybrid is demonstrated to be
      an effective sensor for picric acid. 

PMID- 24079605
TI  - Adipose-derived stem cells for cartilage regeneration--moving towards clinical
      applicability.
AB  - Despite multiple methods of treatment and a wealth of research in the field of
      regenerative medicine focusing on cartilage defects, the management of cartilage
      injuries remains a challenge. A recent study by Van Pham and colleagues proposes
      a method for preconditioning autologous adipose-derived stem cells. Their study
      offers evidence about the increased proliferative and chondrogenetic capabilities
      of platelet-rich plasma-treated adipose-derived stem cells and the increased
      efficiency of these in treating articular cartilage defects in mice. Even though
      the method needs further elaboration and the composition of the repair tissue
      requires investigation, the results are promising for the design of clinically
      acceptable cell therapies aimed at cartilage regeneration.

PMID- 24079606
TI  - Differences in proton-coupled electron-transfer reactions of flavin
      mononucleotide (FMN) and flavin adenine dinucleotide (FAD) between buffered and
      unbuffered aqueous solutions.
AB  - The electrochemical reduction mechanisms of flavin mononucleotide (FMN) in
      buffered aqueous solutions at pH 3-11 and unbuffered aqueous solutions at pH 2-11
      were examined in detail using variable-scan-rate cyclic voltammetry (nu = 0.1-20
      V s(-1)), controlled-potential bulk electrolysis, UV-vis spectroscopy, and
      rotating-disk-electrode voltammetry. In buffered solutions at pH 3-5, FMN
      undergoes a two-electron/two-proton (2e(-)/2H(+)) reduction to form FMNH2 at all
      scan rates. When the buffered pH is increased to 7-9, FMN undergoes a 2e(-)
      reduction to form FMN(2-), which initially undergoes hydrogen bonding with water
      molecules, followed by protonation to form FMNH(-). At a low voltammetric scan
      rate of 0.1 V s(-1), the protonation reaction has sufficient time to take place.
      However, at a higher scan rate of 20 V s(-1), the proton-transfer reaction is
      outrun, and upon reversal of the scan direction, less of the FMNH(-) is available
      for oxidation, causing its oxidation peak to decrease in magnitude. In unbuffered
      aqueous solutions, three major voltammetric waves were observed in different pH
      ranges. At low pH in unbuffered solutions, where [H(+)] >= [FMN], (FMN)H(-)
      undergoes a 2e(-)/2H(+) reduction to form (FMNH2)H(-) (wave 1), similar to the
      mechanism in buffered aqueous solutions at low pH. At midrange pH values
      (unbuffered), where pH <= pKa of the phosphate group and [FMN] >= [H(+)], (FMN)H(
      ) undergoes a 2e(-) reduction to form (FMN(2-))H(-) (wave 2), similar to the
      mechanism in buffered aqueous solutions at high pH. At high pH (unbuffered),
      where pH >= pKa = 6.2 of the phosphate group, the phosphate group loses its
      second proton to be fully deprotonated, forming (FMN)(2-), and this species
      undergoes a 2e(-) reduction to form (FMN(2-))(2-) (wave 3). 

PMID- 24079607
TI  - Complications of Hartmann takedown in a decade of preferred primary anastomosis.
AB  - BACKGROUND: Primary anastomosis with or without proximal diversion is
      increasingly applied to patients requiring urgent colectomy for complicated
      disease of the left colon. As such, the Hartmann procedure is now often
      restricted to patients who are unstable or otherwise poor candidates for primary
      anastomosis. We sought to define the complication rate of Hartmann takedown in a
      contemporary setting. METHODS: Consecutive adult patients undergoing colostomy
      takedown with colorectal anastomosis at an academic teaching hospital from
      January 1, 2001, to December 31, 2010, were included in the study. Complications
      were captured prospectively by a single trained nurse practitioner. Demographics,
      body mass index, American Society of Anesthesiologists (ASA) classification,
      interval between Hartmann procedure and subsequent takedown, surgical indication,
      duration of surgery, surgeon volume and specialty, length of stay, and
      complications were recorded. RESULTS: One hundred three patients underwent
      Hartmann reversal by 16 different surgeons; 7 of these surgeons performed 4 or
      fewer procedures during the study period. During the same time period, 334
      patients underwent a Hartmann procedure at our institution. Seventy-seven of 104
      patients (74%) had their index resection for complicated diverticulitis; an
      anastomotic leak was the second most common indication. The median age was 61
      years (range 31 to 84 years), and the interval from Hartmann procedure to
      reversal ranged from 87 to 1,489 days. Only 8 patients (7.7%) had an ASA of 1.
      Thirty patients (29.1%) had postoperative complications, and 12 (11%) had 2 or
      more complications. There were 2 deaths and 4 anastomotic leaks, and 7 patients
      had inadvertent enterotomies. Only ASA status predicted postoperative
      complications (P = .01). CONCLUSIONS: Hartmann takedown is a morbid operation
      with a substantial risk of inadvertent enterotomy and serious complications.
      Excluding cases referred from elsewhere, there were more than 5-fold the number
      of Hartmann procedures than takedowns performed during the study period. This
      suggests that Hartmann procedures are typically restricted to patients who are
      also poor candidates for takedown and that their colostomy is likely to be
      permanent.

PMID- 24079608
TI  - Exposure to the Chinese famine in early life and the risk of anaemia in
      adulthood.
AB  - BACKGROUND: Famine exposure during the early stage of life is related to a number
      of adulthood diseases. The objective of this study was to examine the association
      of early life exposure to the famine in China (1959-1961) with the risk of
      anaemia in adulthood. METHODS: We used the data of 2007 adults born between 1954
      and 1964 in Jiangsu province from the 2002 Chinese National Nutrition and Health
      Survey. Anaemia was defined as haemoglobin concentration <12 g/dl in women and
      <13 g/dl in men. RESULTS: Prevalence of anaemia in adulthood in nonexposed, fetal
      exposed, early-childhood, mid-childhood, and late-childhood exposed to famine
      groups were 26.0%, 33.8%, 28.1%, 28.2% and 29.7%, respectively. Overall, fetal
      exposed to famine was associated with 37% increased risk of anaemia as compared
      with those non-exposed after adjusting for income, education, place of residence,
      smoking, alcohol drinking, job, hypertension and BMI; relative risk (95%
      confidence interval) (RR (95% CI)) was 1.37 (1.09, 1.71). In general, this
      association appeared to be stronger among men, those who were currently
      overweight or obese, or those of lower educational levels. Corresponding RR (95%
      CI) was 1.87 (1.21-2.87), 1.75 (1.20-2.56), and 2.07 (1.37-3.12), respectively.
      CONCLUSIONS: Fetal exposure to the Chinese famine was associated with an
      increased risk of anaemia in adulthood.

PMID- 24079610
TI  - Engineered nanoparticle adhesion and removal from tomato surfaces.
AB  - Engineered nanoparticles (NPs) are being used in different industries due to
      their unique physicochemical properties. NPs may be toxic and could pose both
      public health and environmental contamination risks. In this study, two
      concentrations (50 and 500 MUg mL(-1)) of titania (TiO2), silica (SiO2), and
      alumina (Al2O3) were applied to contaminate the surface of cherry tomato as a
      food model, followed by washing with deionized water (DI) to remove the NPs from
      the tomato surfaces. The NP surface charge and hydrodynamic diameter results
      showed that the isoelectric point (IEP) for alumina was at pH 9-9.6, for silica
      at pH <3, and for titania was at pH 6.5-6.8; in addition, the highest
      hydrodynamic size for all NPs was observed at the IEP. Inductively coupled plasma
      mass spectrometry (ICP-MS) indicated that the highest NP concentration was
      observed on tomato surfaces contaminated at the higher concentration (500 MUg mL(
      1)) (P < 0.05). After the tomatoes had been washed with DI, alumina levels
      decreased significantly, whereas for titania and silica, no significant
      difference in NP concentration on tomato surface was observed following the
      washing treatment. This study shows that removal of NPs may be possible with a
      simple washing treatment but that removal of NPs is likely to be more effective
      when the moment ratio is >1, which can occur if the pH of the washing solution is
      significantly different from the IEP of NPs. 

PMID- 24079611
TI  - Child-directed action promotes 2-year-olds' imitation.
AB  - Children are voracious learners and adults are ubiquitous teachers. This project
      investigated whether the special infant-directed action modifications parents use
      when teaching their children (called "motionese" by Brand et al., Developmental
      Science, 2002, Vol. 5, pp. 72-83) improves 2-year-olds' imitation. Children saw
      an adult perform a series of acts on four novel objects using either an infant
      directed style (including larger range of motion and enhanced boundary marking)
      or an adult-directed style. Children's imitation of the acts was higher in the
      infant-directed condition relative to the adult-directed condition, and both
      types of demonstration increased imitation relative to baseline (no
      demonstration). We propose that motionese provides information about actions,
      objects, and intentionality, thereby enhancing toddlers' observational learning. 

PMID- 24079612
TI  - Age-associated changes of walking parameters in Japanese adult women.
AB  - Abstract The purpose of this paper is to clarify the age-associated changes in
      walking movements. A two-dimensional movement analysis was conducted on a sample
      of 177 healthy women aged 19 to 82 years, with performance-descriptors,
      kinematics and kinetics as the parameters. An analysis of covariance, with the
      gait velocity as covariate and the categorized age group as a fixed factor, was
      adopted to examine the differences in each parameter among eight age groups. We
      conclude that age-associated changes in walking movement occur due to the
      essential ageing effect in the walking, rather than due to differences in the
      physique or decrease of the gait velocity.

PMID- 24079609
TI  - Translational toxicology: a developmental focus for integrated research
      strategies.
AB  - BACKGROUND: Given that toxicology studies the potential adverse effects of
      environmental exposures on various forms of life and that clinical toxicology
      typically focuses on human health effects, what can and should the relatively new
      term of "translational toxicology" be taken to mean? DISCUSSION: Our assertion is
      that the core concept of translational toxicology must incorporate existing
      principles of toxicology and epidemiology, but be driven by the aim of developing
      safe and effective interventions beyond simple reduction or avoidance of exposure
      to prevent, mitigate or reverse adverse human health effects of exposures.The
      field of toxicology has now reached a point where advances in multiple areas of
      biomedical research and information technologies empower us to make fundamental
      transitions in directly impacting human health. Translational toxicology must
      encompass four action elements as follows: 1) Assessing human exposures in
      critical windows across the lifespan; 2) Defining modes of action and relevance
      of data from animal models; 3) Use of mathematical models to develop plausible
      predictions as the basis for: 4) Protective and restorative human health
      interventions. The discussion focuses on the critical window of in-utero
      development. SUMMARY: Exposure assessment, basic toxicology and development of
      certain categories of mathematical models are not new areas of research; however
      overtly integrating these in order to conceive, assess and validate effective
      interventions to mitigate or reverse adverse effects of environmental exposures
      is our novel opportunity. This is what we should do in translational toxicology
      so that we have a portfolio of interventional options to improve human health
      that include both minimizing exposures and specific
      preventative/restorative/mitigative therapeutics.

PMID- 24079613
TI  - MAPping Los Angeles County: taking an evidence-informed model of mental health
      care to scale.
AB  - We describe the scaling up of an evidence-informed model of care, Managing and
      Adapting Practice (MAP) in Los Angeles County, California. MAP complemented an
      array of evidence-based programs selected by the county as part of a large system
      reform effort designed to improve care for children and adolescents. In addition,
      we discuss the MAP model for training therapists and present data both on how the
      training model performed and on the outcomes of youths treated by therapists
      trained in MAP. We examined the success of two different training pathways for
      MAP therapists: (a) national training model and (b) MAP agency supervisor model
      (i.e., train the trainer). We also examined utilization of MAP and outcomes of
      clients served by MAP. Both the national training and MAP agency supervisor model
      were successful in producing MAP therapists in a timely fashion and with
      acceptable competency scores. Furthermore, a large number of clients were
      receiving MAP services. Finally, outcomes for youth treated with MAP were strong,
      with effect sizes ranging from .59 to .80 on the Youth Outcome Questionnaire.
      These data support the notion that scaling up a mental health services approach
      in a system can be achieved through a strong and broad partnership among relevant
      stakeholders, can involve a train-the-trainer model, and can result in strong
      outcomes for clients. 

PMID- 24079614
TI  - Natural genetic variation determines susceptibility to aggregation or toxicity in
      a C. elegans model for polyglutamine disease.
AB  - BACKGROUND: Monogenic gain-of-function protein aggregation diseases, including
      Huntington's disease, exhibit substantial variability in age of onset,
      penetrance, and clinical symptoms, even between individuals with similar or
      identical mutations. This difference in phenotypic expression of proteotoxic
      mutations is proposed to be due, at least in part, to the variability in genetic
      background. To address this, we examined the role of natural variation in
      defining the susceptibility of genetically diverse individuals to protein
      aggregation and toxicity, using the Caenorhabditis elegans polyglutamine model.
      RESULTS: Introgression of polyQ40 into three wild genetic backgrounds uncovered
      wide variation in onset of aggregation and corresponding toxicity, as well as
      alteration in the cell-specific susceptibility to aggregation. To further dissect
      these relationships, we established a panel of 21 recombinant inbred lines that
      showed a broad range of aggregation phenotypes, independent of differences in
      expression levels. We found that aggregation is a transgressive trait, and does
      not always correlate with measures of toxicity, such as early onset of muscle
      dysfunction, egg-laying deficits, or reduced lifespan. Moreover, distinct
      measures of proteotoxicity were independently modified by the genetic background.
      CONCLUSIONS: Resistance to protein aggregation and the ability to restrict its
      associated cellular dysfunction are independently controlled by the natural
      variation in genetic background, revealing important new considerations in the
      search for targets for therapeutic intervention in conformational diseases. Thus,
      our C. elegans model can serve as a powerful tool to dissect the contribution of
      natural variation to individual susceptibility to proteotoxicity.Please see
      related commentary by Kaeberlein, http://www.biomedcentral.com/1741-7007/11/102.

PMID- 24079615
TI  - Current surgical instrument labeling techniques may increase the risk of
      unintentionally retained foreign objects: a hypothesis.
AB  - BACKGROUND: Marking of surgical instruments is essential to ensure their proper
      identification after sterile processing. The National Quality Forum defines
      unintentionally retained foreign objects in a surgical patient as a serious
      reportable event also called "never event." PRESENTATION OF THE HYPOTHESIS: We
      hypothesize that established practices of surgical instrument identification
      using unkempt tape labels and plastic tags may expose patients to "never events"
      from retained disintegrating labels. TESTING OF THE HYPOTHESIS: We demonstrate
      the near miss of a "never event" during a surgical case in which the breakage of
      an instrument label remained initially unwitnessed. A fragment of the plastic
      label was accidentally found in the wound upon closing. Further clinical testing
      of the occurrence of this "never event" appears not feasible. As the name implies
      a patient should never be exposed to the risk of fragmenting labels. IMPLICATION
      OF THE HYPOTHESIS: Current practice does not mandate verifying intact instrument
      markers as part of the instrument count. The clinical confirmation of our
      hypothesis mandates a change in perioperative practice: Mechanical labels need to
      undergo routine inspection and maintenance. The perioperative count must not only
      verify the quantity of surgical instruments but also the intactness of labels to
      ensure that no part of an instrument is left behind. Proactive maintenance of
      taped and dipped labels should be performed routinely. The implementation of
      newer labeling technologies - such as laser engraved codes - appears to eliminate
      risks seen in traditional mechanical labels.This article reviews current
      instrument marking technologies, highlights shortcomings and recommends safe
      instrument handling and marking practices implementing newer available
      technologies.

PMID- 24079616
TI  - Influenza: a scientometric and density-equalizing analysis.
AB  - BACKGROUND: Novel influenza in 2009 caused by H1N1, as well as the seasonal
      influenza, still are a challenge for the public health sectors worldwide. An
      increasing number of publications referring to this infectious disease make it
      difficult to distinguish relevant research output. The current study used
      scientometric indices for a detailed investigation on influenza related research
      activity and the method of density equalizing mapping to make the differences of
      the overall research worldwide obvious. The aim of the study was to compare
      scientific effort over the time as well as geographical distribution including
      the cooperation on national and international level. METHODS: Therefore,
      publication data was retrieved from Web of Science (WoS) of Thomson Scientific.
      Subsequently the data was analysed in order to show geographical distributions
      and the development of the research output over the time.The query retrieved
      51,418 publications that are listed in WoS for the time interval from 1900 to
      2009. There is a continuous increase in research output and general citation
      activity especially since 1990. RESULTS: The identified all in all 51,418
      publications were published by researchers from 151 different countries.
      Scientists from the USA participate in more than 37 percent of all publications,
      followed by researchers from the UK and Germany with more than five percent. In
      addition, the USA is in the focus of international cooperation.In terms of number
      of publications on influenza, the Journal of Virology ranks first, followed by
      Vaccine and Virology. The highest impact factor (IF 2009) in this selection can
      be established for The Lancet (30.75). Robert Webster seems to be the most
      prolific author contributing the most publications in the field of influenza.
      CONCLUSIONS: This study reveals an increasing and wide research interest in
      influenza. Nevertheless, citation based-declaration of scientific quality should
      be considered critically due to distortion by self-citation and co-authorship.

PMID- 24079617
TI  - Organocatalytic cascade sulfa-Michael/aldol reaction of beta,beta-disubstituted
      enones: enantioselective synthesis of tetrahydrothiophenes with a
      trifluoromethylated quaternary center.
AB  - A bifunctional squaramide-catalyzed sulfa-Michael/aldol cascade reaction
      initiated by sulfa-Michael addition of mercaptoacetaldehyde to beta-aryl-beta
      trifluoromethylated enones is successfully developed. The functionalized
      tetrahydrothiophenes with three continuous stereocenters including a
      trifluoromethylated quaternary carbon are readily obtained with moderate to good
      yields and high enantioselectivities. 

PMID- 24079618
TI  - Adrenaline and amiodarone dosages in resuscitation: rectifying misinformation.
AB  - Despite the recognition of specialists in emergency medicine and the
      professionalisation of prehospital emergency care, international guidelines and
      consensus are often ignored, and the lag between guideline publication and
      translation into clinical practice is protracted. South African literature should
      reflect the latest evidence to guide resuscitation and safe patient care. This
      article addresses erroneous details regarding life-saving interventions in the
      South African Medicines Formulary, 10th edition.  

PMID- 24079619
TI  - Isoniazid preventive therapy in HIV-infected and -uninfected children (0 - 14
      years).
AB  - Isoniazid preventive therapy (IPT) prevents tuberculosis (TB) in immunocompetent
      children <5 years of age after exposure to an infectious TB source case. Routine
      IPT has been advocated in all HIV-infected children without TB, but has been
      controversial. Antiretroviral therapy markedly reduces the risk for TB in HIV
      infected children, especially when started early in infancy. In HIV-infected
      children, as in HIV- uninfected children, we recommend post-exposure IPT after
      each TB exposure episode; but in HIV-infected children, this should be given
      irrespective of age or antiretroviral therapy. However, evidence for routine IPT
      without known exposure to TB in HIV-infected children is not convincing and is
      therefore not recommended.  

PMID- 24079620
TI  - Urban food insecurity: a neglected public health challenge.

PMID- 24079621
TI  - South Africa's nutritional transition: overweight, obesity, underweight and
      stunting in female primary school learners in rural KwaZulu-Natal, South Africa.
AB  - BACKGROUND: Malnutrition substantially impacts the health outcomes of children.
      Globally, the childhood prevalence of overweight and obesity has increased, while
      underweight and stunting (though decreasing) continues to pose a major public
      health challenge. In low- to middle-income countries, a mixed pattern of over-
      and undernutrition (nutritional transition) can exist in communities. OBJECTIVE:
      To describe the prevalence of malnutrition among female learners in the Nongoma
      and Ceza districts in Zululand, KwaZulu-Natal (KZN). METHODS: We performed a
      secondary analysis of anthropometric data collected during the 2011 HPV
      Vaccination Demonstration Project. School health teams, comprising trained
      nurses, measured the height (in cm) and weight (in kg) of 963 female learners in
      31 primary schools. Internationally accepted standardised measures were used as
      cut-offs for defining overweight, obesity, underweight and stunting. RESULTS: We
      found evidence of both under- and overnutrition. Overall, 9% of female learners
      were overweight, 3.8% obese, 4% underweight and 9.2% stunted (using WHO/NCHS
      criteria). The highest levels of stunting were in the 11 - 12-year age groups, of
      underweight in the 10-year age group, of overweight and obesity in the 9 - 10
      year age groups. Moreover, a proportion of underweight (17.4%), overweight
      (11.1%) and obese (22.9%) learners were also stunted. CONCLUSION: Our study
      describes the prevalence of overweight and obesity, wasting and stunting of
      female learners in KZN and suggests the presence of a nutritional transition in
      these rural communities; however, further studies are needed. Our findings
      emphasise the need for health promotion and education programs in schools.

PMID- 24079622
TI  - Emergency centre investigation of first-onset seizures in adults in the Western
      Cape, South Africa.
AB  - BACKGROUND: Patients with first-onset seizures commonly present to emergency
      centres (ECs). The differential diagnosis is broad, potentially life-threatening
      conditions need to be excluded, and these patients need to be correctly diagnosed
      and appropriately referred. There are currently no data on adults presenting with
      first-onset seizures to ECs in South Africa. OBJECTIVE: To review which
      investigations were performed on adults presenting with first-onset seizures to
      six ECs in the Western Cape Province. METHODS: A prospective, cross-sectional
      study was conducted from 1 July 2011 to 31 December 2011. All adults with first
      onset seizures were included; children and trauma patients were excluded.
      Subgroup analyses were conducted regarding HIV status and inter-facility
      variation. RESULTS: A total of 309 patients were included. Computed tomography
      (CT) scans were planned in 218 (70.6%) patients, but only performed in 169; 96
      (56.8%) showed abnormalities judged to be causative (infarction, intracerebral
      haemorrhage and atrophy being the most common). At least 80% of patients (n=247)
      received a full renal and electrolyte screen, blood glucose testing and a full
      haematological screen. Lumbar puncture (LP) was performed in 67 (21.7%) patients,
      with normal cerebrospinal fluid findings in 51 (76.1%). Only 27 (8%) patients had
      an electroencephalogram, of which 5 (18%) were abnormal. There was a
      statistically significant difference in the number of CT scans (p=0.002) and LPs
      (p<0.001) performed in the HIV-positive group (n=49). CONCLUSION: This study
      demonstrated inconsistency and wide local variance for all types of
      investigations done. It emphasises the need for a local guideline to direct
      doctors to appropriate investigations, ensuring better quality patient care and
      potential cost-saving.

PMID- 24079623
TI  - Management of undifferentiated embryonal sarcoma of the liver in children: a case
      series and management review.
AB  - BACKGROUND: Undifferentiated embryonal sarcoma of the liver (UESL) is a rare
      neoplasm, and the third-most common paediatric hepatic malignancy. However, no
      treatment guidelines exist. No randomised, controlled trials support specific
      combinations of therapy. OBJECTIVE: To compare presentation and management of
      UESL with other series, review the literature, and formulate treatment
      guidelines. METHODS: A retrospective chart review of all hepatic malignancies was
      conducted from 1996 to 2007 and 5 children with UESL were identified. Management
      and outcomes were documented. The literature regarding treatment modalities up to
      September 2012 was reviewed. RESULTS: Over a period of 11 years, 5 patients
      presented. All underwent surgery and 4 received chemotherapy. One received
      radiotherapy at relapse. Three are disease-free with follow-up of 58 - 184
      months. One died after relapse, as did the patient whose family declined
      chemotherapy. CONCLUSION: The improved outcomes are consistent with the
      international experience and are probably related to combined treatment
      modalities and advances in supportive care. Pre-operative percutaneous biopsy
      provides no benefit if the lesion is resectable because it may not prove to be
      diagnostic, and may cause recurrence in the biopsy tract. If resectable, the
      recommended treatment is primary excision and adjuvant chemotherapy, with
      radiotherapy in selected cases. If unresectable, open biopsy is necessary to
      document histology, and neo- adjuvant chemotherapy is given prior to resection.
      If deemed unresectable, liver transplantation is considered.

PMID- 24079624
TI  - The versatility of median sternotomy in general paediatric surgery.
AB  - BACKGROUND: While common in cardiac surgery, median sternotomy (MS) is rarely
      required in general paediatric surgery. In the era of advancing endoscopic
      techniques, sternotomy is perceived as an extremely invasive incision, associated
      with prolonged postoperative recovery and significant morbidity. METHODS: We
      conducted a retrospective chart review of all children undergoing MS for non
      cardiac indications between January 2007 and September 2012 and describe the
      pathology, number of ventilated days, duration of intensive care unit stay and
      analgesic requirements. RESULTS: Our experience over the past 6 years includes 14
      children, aged between 8 months and 13 years. Indications for surgery included
      penetrating mediastinal trauma (1), anterior and posterior mediastinal masses
      (4), acquired tracheo-oesophageal fistulas secondary to button battery impaction
      (2), bronchial foreign bodies (2) and bilateral pulmonary metastases secondary to
      malignancy (5). The range of postoperative ventilation required was 0 - 34 days
      (median 1 day) and the range of duration of stay in the paediatric intensive care
      unit 1 - 39 days (median 4 days). Postoperative analgesia was provided with
      intravenous or oral paracetamol with or without the addition of morphine. All the
      children tolerated the procedure well with no sternotomy-related complications on
      follow-up. CONCLUSION: This review highlights the variety of conditions in which
      MS provides unrivalled access to the mediastinum and how well the procedure is
      tolerated by the paediatric patient, and emphasises the importance of sternotomy
      being within the armamentarium of access techniques of the general paediatric
      surgeon.

PMID- 24079625
TI  - Rapid, minimally invasive adult voluntary male circumcision: A randomised trial.
AB  - BACKGROUND: Voluntary medical male circumcision (VMMC) is a priority HIV
      preventive intervention. To facilitate male circumcision scale- up, the World
      Health Organization is actively seeking circumcision techniques that are quicker,
      easier, and safer than open surgical methods. OBJECTIVE: To compare conventional
      open surgical circumcision with suturing with a minimally invasive technique
      using the Gomco circumcision clamp plus tissue adhesive. METHODS: We conducted a
      non-blinded randomised controlled trial comprising 200 male volunteers >18 years
      of age, seen at the outpatient university teaching clinic of the Catholic
      University of Mozambique. We compared two interventions - open surgical
      circumcision with suturing v. Gomco instrument plus tissue adhesive. Our primary
      outcome was intraoperative time and our secondary outcomes included: ease of
      performance, post-operative pain, adverse events, time to healing, patient
      satisfaction and cosmetic result. RESULTS: The intraoperative time was less with
      the Gomco/tissue adhesive technique (mean 12.8 min v. 22.5 min; p<0.001). Adverse
      events were similar except that wound disruption was greater in the Gomco/tissue
      adhesive group, with no difference in wound healing at 4 weeks. Levels of
      satisfaction were high in both groups. The cosmetic result was superior in the
      Gomco/tissue adhesive group. CONCLUSIONS: This study has important implications
      for the scale-up of VMMC services. Removing the foreskin with the Gomco
      instrument and sealing the wound with cyanoacrylate tissue adhesive in adults is
      quicker, is an easier technique to learn, and is potentially safer than open
      surgical VMMC. A disposable plastic, Gomco-like device should be produced and
      evaluated for use in resource-limited settings.

PMID- 24079626
TI  - Quantifying the disparity in outcome between urban and rural patients with acute
      appendicitis in South Africa.
AB  - BACKGROUND: Acute appendicitis in South Africa is associated with higher
      morbidity than in the developed world. Objective. To compare outcomes of urban
      and rural patients in KwaZulu-Natal and to determine whether there are
      disparities in outcome. METHODS: We conducted a prospective study from September
      2010 to September 2012 at Edendale Hospital in Pietermaritzburg, South Africa.
      All patients who presented with acute appendicitis were included. The operative
      and clinical course of urban and rural patients was compared. Results. A total of
      500 patients were included, with 200 patients in the rural group and 300 in the
      urban group. Those from the rural group had a significantly longer duration of
      symptoms prior to presentation. All septic parameters were significantly worse in
      the rural group. Significantly more patients from the rural group required a
      laparotomy (77% v. 51% urban; p<0.001). Inflamed, non-perforated appendicitis was
      more commonly seen in the urban group (52.3% v. 21% rural; p<0.001), while
      perforated appendicitis was much more common in the rural group (79% v. 47.7%
      urban; p<0.001). Perforation associated with generalised, four-quadrant intra
      abdominal contamination was significantly higher in the rural group than the
      urban group (60.5% v. 21%, respectively; p<0.05). Significantly more patients
      from the rural group required an open abdomen (46% v. 12% urban; p<0.001) and >=1
      re-laparotomies to control severe intra-abdominal sepsis (60.5% v. 23.3% urban;
      p<0.001). CONCLUSION: We have identified rural origin as an independent indicator
      of poor outcome. Possible reasons may include difficulty in accessing the health
      system or delay in transfer to a regional hospital. These need to be investigated
      further.

PMID- 24079627
TI  - The South African Vascular Surgical Cardiac Risk Index (SAVS-CRI): a prospective
      observational study.
AB  - BACKGROUND: Recent evidence suggests that application of the Revised Cardiac Risk
      Index (RCRI) for peri-operative cardiovascular risk stratification in vascular
      surgery patients may be inappropriate, necessitating the development of risk
      indices specific to vascular surgery patients. OBJECTIVES: To identify risk
      factors for cardiovascular morbidity and mortality in South African patients
      undergoing major vascular surgery, and to develop an appropriate cardiovascular
      risk stratification index, the South African Vascular Surgical Cardiac Risk Index
      (SAVS-CRI), which could be used to predict the risk of peri-operative major
      adverse cardiovascular events (MACEs) in South African vascular surgery patients.
      METHODS: We prospectively collected data related to peri-operative MACE
      occurrence and established risk factors for peri-operative MACEs from adult
      patients who underwent elective vascular surgery at a tertiary hospital in
      Durban, South Africa, between February 2008 and March 2011. We determined
      independent predictors of peri-operative MACEs in our cohort by binary logistic
      regression and used the identified predictors to create a risk index that
      stratified patients into low-, intermediate- or high-risk groups. RESULTS: Six
      independent predictors of peri-operative MACEs were identified in the vascular
      surgery cohort: age >65 years, a history of ischaemic heart disease, a history of
      diabetes, chronic beta-blockade, prior coronary revascularisation, and the
      vascular surgical procedure. The risk model derived from these risk factors
      appeared to discriminate between the three risk groups more accurately than the
      RCRI. CONCLUSION: The RCRI is not appropriate for peri-operative cardiovascular
      risk stratification in vascular surgery patients. The SAVS-CRI may be preferable
      for risk stratification in South African vascular surgery patients, although
      independent validation is required.

PMID- 24079628
TI  - A critical analysis of ICU/HC beds in South Africa: 2008-2009.
AB  - OBJECTIVE: To determine the national distribution of intensive care unit
      (ICU)/high care (HC) beds and the implications for ICU bed availability in the
      envisaged national health insurance (NHI) scheme. METHODS: A descriptive, non
      interventional, observational study design was used. A desk-top audit of all
      public and private sector ICUs, including ICU/HC beds, in South Africa was
      undertaken for the period 2008 - 2009. For this study, both categories were
      analysed and referred to as ICU beds, as they reflect the critical care component
      of the health service in South Africa. RESULTS: In 2008 - 2009, there were 4 719
      ICU beds in the private and public sectors in South Africa, with 75% (3 533) in
      the former and 25% (1 186) in the latter. The majority of ICU beds in the two
      sectors were located in three provinces: Gauteng (49%), KwaZulu-Natal (14%) and
      Western Cape (15%), representing 78% of ICU beds (3 703/4 719) and catering for
      54% of the country's population. Eastern Cape had fewer than 300 beds, North West
      and Mpumalanga had fewer than 150 beds, and Limpopo and Northern Cape had 66 and
      47 beds respectively. With the proposed NHI scheme, the number of ICU beds
      available would be 4 719, which would translate into a bed:population ratio of
      approximately 1:10 000. However, there are large variations across the provinces,
      which makes the availability of this level of care in some provinces non
      existent. CONCLUSION: While increasing the number of ICU beds in the public
      sector will open critical care services to more users, the NHI scheme would not
      solve the huge discrepancies of access to ICUs, and availability of critical care
      staff, across the provinces.

PMID- 24079629
TI  - Intra-operative cell salvage in South Africa: feasible, beneficial and
      economical.
AB  - BACKGROUND: Healthcare services in KwaZulu-Natal (KZN) frequently experience
      shortages of blood products. Alternatives to traditional blood sources are
      needed. One possibility is cell salvage and autologous blood transfusion. Few
      data exist relating to their use in the South African context. OBJECTIVES: To
      ascertain whether cell salvage (CS) is beneficial, feasible and economical in our
      setting, with the anticipation that results would excite further studies and
      potentially change current practice and improve existing protocols. Methods. This
      study reviewed current intraoperative Cell Saver use at Grey's and Edendale
      hospitals in Pietermaritzburg, KZN. Current practices were observed and compared
      with the costs of the equivalent amount of red cell concentrate (RCC) purchased
      from the South African National Blood Service (SANBS). All cases of Cell Saver
      usage over a 1-year period from July 2012 to June 2013 were analysed. RESULTS:
      The total volume of blood transfused from CS was 55 735 ml, approximately
      equivalent to 186 RCC units. The comparative cost of equivalent units of RCC from
      SANBS was R258 445. The total cost of Cell Saver disposables during the study
      period was R206 047, or R263 478 when Cell Saver machine depreciation costs were
      included. More than one CS blood unit was available for transfusion in 66% of
      cases. No additional staff were required to operate the Cell Saver, which was
      successfully used by medical officers. CONCLUSIONS: This study showed that
      intraoperative CS use is feasible, has potential patient benefit by reducing
      blood bank blood transfusion, and is financially comparable to purchasing the
      equivalent number of SANBS RCC.

PMID- 24079630
TI  - HIV-associated neurocognitive disorders: antiretroviral regimen, central nervous
      system penetration effectiveness, and cognitive outcomes.
AB  - BACKGROUND: The human immunodeficiency virus (HIV) can give rise to a spectrum of
      neuropsychological impairments known collectively as HIV-associated
      neurocognitive disorders (HAND). Although antiretroviral therapy (ART) has
      reduced the incidence of HIV dementia, the prevalence of milder forms of HAND has
      increased. It has been postulated that incomplete central nervous system (CNS)
      viral suppression or potential drug toxicity, both of which could be related to
      the CNS penetration effectiveness (CPE) of ART regimens, may contribute to this
      phenomenon. OBJECTIVE: This study compared cognitive outcomes in clade C-infected
      HIV patients in South Africa treated for 1 year with ART regimens with differing
      CPE scores. METHODS: We assessed 111 HIV-positive patients with varying levels of
      cognitive function at baseline (pre-ART) and then a year later. A
      neuropsychological battery was administered at both visits to derive global
      deficit scores. ART regimen data were collected at the follow-up visit. Some
      participants remained ART-naive during this period, thus providing a non
      treatment control group. RESULTS: Significantly more ART recipients maintained or
      improved cognitive function compared with patients not on ART (p=0.017). There
      was no significant difference in cognitive outcomes between higher and lower CPE
      regimen groups (p=0.473). CONCLUSIONS: ART preserves or improves cognition in HIV
      infected patients after 1 year, irrespective of the regimen's CPE. South Africa's
      current low CPE-scored first-line regimen performed as well as higher CPE-scored
      regimens. These findings are reassuring for South Africa, but larger, longer-term
      studies would be more definitive.

PMID- 24079631
TI  - HPCSA serious injury narrative test guideline.
AB  - Current South African Road Accident Fund (RAF) legislation requires a medical
      determination of the seriousness of injuries sustained in motor vehicle accidents
      to determine whether the claimant is entitled to a claim for general damages.
      Such medical assessments are submitted in the form of RAF 4 Serious Injury
      Assessment Reports. Contested claims for serious injury are referred to the
      Health Professions Council of South Africa (HPCSA) Appeal Tribunals for final
      determination. The legislation prescribes 2 instruments, namely the American
      Medical Association (AMA) Guides (6th edition) and the Narrative Test for this
      purpose. Whereas the AMA Guides are published in a comprehensive book, and
      training courses are provided in their use, existing legislation does not provide
      any indication of the required structure, content or criteria of a Narrative Test
      report. This document is published by the HPCSA Appeal Tribunals as a guideline
      to the performance of the Narrative Test; what it is, reasons for applying it and
      who should compile it, as well as the required structure, content and criteria
      thereof. A Narrative Test Report should include relevant and meaningful comment
      in relation to each of the 6 sections described in the article.  

PMID- 24079632
TI  - Malaria in South Africa: 110 years of learning to control the disease.
AB  - In Africa today, the drive towards controlling malaria is comparable with efforts
      made in the 1950s and 1960s during the World Health Organization's Global Malaria
      Eradication Campaign. Unlike the Eradication Campaign that 'covered' the globe
      but excluded Africa, the current endeavours focus on Africa, but not to the
      exclusion of the rest of the tropical and sub-tropical world. Major donor
      agencies are partnering with African governments in an attempt to curb
      transmission of malaria parasites, and in some countries on the edges of the
      distribution of malaria, there is talk of eliminating the disease. South Africa
      is at the very southernmost fringe of malaria distribution on the African
      continent and has a long history of intense malaria control activities. This
      article looks at what South Africa has achieved in the past and where it needs to
      go in the future, not only to maintain the status quo, but hopefully to eliminate
      transmission of the disease within its borders.  

PMID- 24079633
TI  - Epidemiology of malaria in South Africa: from control to elimination.
AB  - Locally specific epidemiological understanding is pivotal to the success of
      malaria elimination in South Africa. Here, we focus on how the host, vector,
      parasite and environment and their interactions have influenced malaria incidence
      in South Africa between 1995 and 2012. Broad environmental considerations are
      necessary, including the physical (temperature and humidity), social (migration
      patterns), economic (quality of housing stock) and political (regional
      collaboration).  

PMID- 24079634
TI  - Malaria vector control in South Africa.
AB  - Malaria vector control is primarily insecticide based and relies on indoor
      residual spraying (IRS) and the distribution of long-lasting insecticide-treated
      bednets (LLINs). These interventions have generally proved effective where
      appropriately implemented. However, the increasing incidence of insecticide
      resistance in target vector populations can, and in several cases already has,
      undermined the effectiveness of IRS and LLINs. Today there are very few
      localities on the African continent where populations of vector mosquitoes are
      still susceptible to the approved classes of insecticides. If elimination is to
      be achieved, SA needs to invest more resources into malaria control.  

PMID- 24079635
TI  - Case management of malaria: diagnosis.
AB  - Laboratory diagnosis of malaria in South Africa has traditionally relied on
      microscopic examination of stained blood films. More recently, rapid diagnostic
      tests (RDTs) have been introduced into routine use, and molecular methods like
      polymerase chain reaction are useful in certain situations. As with all
      laboratory tests, each technique has its advantages and disadvantages. Microscopy
      and RDTs, if appropriately quality assured, are adequate for clinical case
      management. For elimination, active surveillance will need to be expanded
      substantially, with wider use of more sensitive diagnostic nucleic acid
      amplification techniques, and/or serology. To facilitate surveillance activities,
      techniques suitable for field or near-field use would be ideal. A long-running
      external quality assessment programme in South Africa has shown some deficiencies
      in the quality of malaria diagnosis in routine laboratories. Quality systems
      across the spectrum of diagnostic facilities in South Africa need strengthening,
      to ensure progress towards elimination.  

PMID- 24079636
TI  - Case management of malaria: treatment and chemoprophylaxis.
AB  - Malaria case management is a vital component of programmatic strategies for
      malaria control and elimination. Malaria case management encompasses prompt and
      effective treatment to minimise morbidity and mortality, reduce transmission and
      prevent the emergence and spread of antimalarial drug resistance. Malaria is an
      acute illness that may progress rapidly to severe disease and death, especially
      in non-immune populations, if not diagnosed early and promptly treated with
      effective drugs. In this article, the focus is on malaria case management,
      addressing treatment, monitoring for parasite drug resistance, and the impact of
      drug resistance on treatment policies; it concludes with chemoprophylaxis and
      treatment strategies for malaria elimination in South Africa.  

PMID- 24079637
TI  - Health promotion: from malaria control to elimination.
AB  - Here we reflect on the achievement of some of the diverse activities that have
      brought malaria under control, highlight key challenges and propose specific
      health promotion interventions required to move South Africa's malaria programme
      from control to elimination. 

PMID- 24079638
TI  - What will move malaria control to elimination in South Africa?
AB  - In this supplement, several authors have shared lessons from the past and
      identified factors that led to the significant reductions in malaria morbidity
      and mortality during the past half-century in South Africa. In addition,
      strategies for achieving malaria elimination have been proposed. Here, we
      highlight the gaps that have been identified and make proposals for taking South
      Africa from malaria control to elimination. 

PMID- 24079639
TI  - Foreword. South Africa.

PMID- 24079641
TI  - Complex interventions-how should systematic reviews of their impact differ from
      reviews of simple or complicated interventions?

PMID- 24079640
TI  - Epidemiology of critically ill patients in intensive care units: a population
      based observational study.
AB  - INTRODUCTION: Epidemiologic assessment of critically ill people in Intensive Care
      Units (ICUs) is needed to ensure the health care system can meet current and
      future needs. However, few such studies have been published. METHODS: Population
      based analysis of all adult ICU care in the Canadian province of Manitoba, 1999
      to 2007, using administrative data. We calculated age-adjusted rates and trends
      of ICU care, overall and subdivided by age, sex and income. RESULTS: In 2007,
      Manitoba had a population of 1.2 million, 118 ICU beds in 21 ICUs, for 9.8 beds
      per 100,000 population. Approximately 0.72% of men and 0.47% of women were
      admitted to ICUs yearly. The age-adjusted, male:female rate ratio was 1.75 (95%
      CI 1.64 to 1.88). Mean age was 64.5 +/- 16.4 years. Rates rose rapidly after age
      40, peaked at age 75 to 80, and declined for the oldest age groups. Rates were
      higher among residents of lower income areas, for example declining from 7.9 to
      4.4 per 100,000 population from the poorest to the wealthiest income quintiles (p
      <0.0001). Rates of ICU admission slowly declined over time, while cumulative
      yearly ICU bed-days slowly rose; changes were age-dependent, with faster declines
      in admission rates with older age. There was a high rate of recidivism; 16% of
      ICU patients had received ICU care previously. CONCLUSIONS: These temporal trends
      in ICU admission rates and cumulative bed-days used have significant implications
      for health system planning. The differences by age, sex and socioeconomic status,
      and the high rate of recidivism require further research to clarify their causes,
      and to devise strategies for reducing critical illness in high-risk groups.

PMID- 24079642
TI  - Effective writing and publishing scientific papers, part VIII: references.

PMID- 24079643
TI  - Introducing conceptual and analytical clarity on dimensions of complexity in
      systematic reviews of complex interventions.

PMID- 24079644
TI  - Smoking exposure induces human lung endothelial cell adaptation to apoptotic
      stress.
AB  - Prolonged exposure to cigarette smoking is the main risk factor for emphysema, a
      component of chronic obstructive pulmonary diseases (COPDs) characterized by
      destruction of alveolar walls. Moreover, smoking is associated with pulmonary
      artery remodeling and pulmonary hypertension, even in the absence of COPD,
      through as yet unexplained mechanisms. In murine models, elevations of intra- and
      paracellular ceramides in response to smoking have been implicated in the
      induction of lung endothelial cell apoptosis, but the role of ceramides in human
      cell counterparts is yet unknown. We modeled paracrine increases (outside-in) of
      palmitoyl ceramide (Cer16) in primary human lung microvascular cells. In naive
      cells, isolated from nonsmokers, Cer16 significantly reduced cellular
      proliferation and induced caspase-independent apoptosis via mitochondrial
      membrane depolarization, apoptosis-inducing factor translocation, and poly(ADP
      ribose) polymerase cleavage. In these cells, caspase-3 was inhibited by ceramide
      induced Akt phosphorylation, and by the induction of autophagic microtubule
      associated protein-1 light-chain 3 lipidation. In contrast, cells isolated from
      smokers exhibited increased baseline proliferative features associated with lack
      of p16(INK4a) expression and Akt hyperphosphorylation. These cells were resistant
      to Cer16-induced apoptosis, despite presence of both endoplasmic reticulum stress
      response and mitochondrial membrane depolarization. In cells from smokers, the
      prominent up-regulation of Akt pathways inhibited ceramide-triggered apoptosis,
      and was associated with elevated sphingosine and high-mobility group box 1,
      skewing the cell's response toward autophagy and survival. In conclusion, the
      cell responses to ceramide are modulated by an intricate cross-talk between Akt
      signaling and sphingolipid metabolites, and profoundly modified by previous
      cigarette smoke exposure, which selects for an apoptosis-resistant phenotype. 

PMID- 24079645
TI  - Comparison of the hypoglycemic effect of sitagliptin versus the combination of
      mitiglinide and voglibose in drug-naive Japanese patients with type 2 diabetes.
AB  - OBJECTIVE: The postprandial glucose (PPG) level is reduced by alpha-GIs, glinides
      and DPP4Is through different pharmacological actions. The aim of this study was
      to compare the effect of sitagliptin (S) versus that of the combination of
      mitiglinide and voglibose (M+V) on markers of glycemic control. RESEARCH DESIGN
      AND METHODS: A randomized cross-over trial was performed in 20 patients with drug
      naive type 2 diabetes. The patients were randomized to receive S (50 mg/day) or
      M+V (1 tablet 3 times daily). Treatment was continued for 8 weeks, after which
      they were switched to the other regimen and treated for another 8 weeks. At
      baseline, after the first regimen, and after the second regimen, a meal test was
      performed. MAIN OUTCOME MEASURES: The markers of glycemic control were examined.
      RESULTS: Reduction of glucose excursion was significantly greater with M+V than
      with S. HbA1c did not change with either regimen. However, 1,5-anhydroglucitol
      showed a significant increase from baseline with both regimens (7.9 +/- 4.3
      MUg/ml at baseline vs. 10.6 +/- 5.5 with S, p < 0.05 and 15.1 +/- 6.2 with M+V, p
      < 0.01). Compared with baseline, glycoalbumin was significantly reduced by M+V,
      but not S (19.6 +/- 2.9% at baseline vs. 17.3 +/- 3.8% with M+V, p < 0.05).
      CONCLUSION: M+V achieved better control of PPG excursion than S.

PMID- 24079646
TI  - Electroanalytical evaluation of antioxidant activity of cerium oxide
      nanoparticles by nanoparticle collisions at microelectrodes.
AB  - We describe a simple, cost-effective and rapid electrochemical screening approach
      to evaluate antioxidant activity of cerium oxide nanoparticles (CeO2 NPs) by
      single nanoparticle collision at microelectrodes. The method is based on direct
      monitoring of the interaction between a Pt microelectrode and surface bound
      superoxo and peroxo anions of CeO2 NPs (Ce-O2(-)/O2(2-)) formed upon exposure to
      H2O2, selected here as a model reactive oxygen species. We observe an increase in
      spike current frequency for CeO2 NPs exposed to H2O2, which we attribute to the
      reduction of surface bound oxygen species when the particles collide with the
      microelectrode. The results were confirmed with spectroscopic techniques that
      demonstrate changes in surface reactivity and composition. The spike frequency
      was found to correlate well with the superoxide dismutase activity of these
      particles. This approach could enable routine screening of antioxidant NPs using
      a rapid and inexpensive assay. 

PMID- 24079647
TI  - An intervention to improve mental health and family well-being of injecting drug
      users and family members in Vietnam.
AB  - Family plays an important role in the lives of injecting drug users (IDUs) in
      Vietnam. This study examined the preliminary outcomes of an intervention
      targeting IDUs and their family members in Vietnam. Eighty-three families,
      including 83 IDUs and 83 family members, were recruited from 4 communes in Phu
      Tho Province, Vietnam. The 4 communes were randomized to either an intervention
      condition or a standard care condition. The IDUs and their family members in the
      intervention condition completed 4 group sessions, with the aims to improve their
      mental health and family relations and to promote positive behavioral change. The
      intervention effect was evaluated at baseline and 3- and 6-month follow-up
      assessments. A significant reduction in depressive symptoms and improvement in
      family functioning were reported for IDUs in the intervention group compared with
      those in the standard care group. The family members in the intervention group
      reported better coping skills at 3 months, fewer depressive symptoms at 6 months,
      and improved family function at both 3 and 6 months compared with those in the
      standard care group. However, no significant intervention effect was observed for
      IDUs in terms of drug-using behavior. This study demonstrates the feasibility and
      preliminary outcomes of an intervention that simultaneously targets IDUs and
      their family members in Vietnam. Study findings highlight the importance of
      including family members and enhancing their role in drug use intervention
      efforts.

PMID- 24079649
TI  - Identifying the factor structure of the SOCRATES in a sample of Latino
      adolescents.
AB  - The Stages of Change Readiness and Treatment Eagerness Scale (SOCRATES) is a
      frequently used measure to assess client motivation to change an alcohol use
      problem. The factor structure of this measure has most extensively been studied
      in samples of adult clients with alcohol use disorders with very little research
      conducted with adolescents or ethnic minority participants. The purpose of the
      current study is to determine if the factor structure of the SOCRATES (Version 8A
      Alcohol) found in prior research can be generalized to a sample of Latino
      adolescents with substance use disorders. Latino adolescents (N = 106) were
      administered the SOCRATES and assessed for alcohol use at a pretreatment baseline
      assessment as part of a larger study. Competing factor models were tested and
      results via confirmatory factor analysis indicated that a 14-item two factor
      model best fit the data for the Latino adolescents in this sample. In addition,
      scores on the Taking Steps factor predicted alcohol use variables. Implications
      for these results and suggestions for further research are discussed.

PMID- 24079648
TI  - Use of protective behavioral strategies and reduced alcohol risk: examining the
      moderating effects of mental health, gender, and race.
AB  - Recent research indicates that protective behavioral strategies (PBS)-previously
      established as effective self-regulating tools for reducing alcohol risk among
      college students-may be especially useful for students with poor mental health,
      who are shown to be at heightened risk for alcohol-related harm. The current
      study examined the moderating influence of mental health (depression and anxiety
      severity), gender, and race (White, Asian) in the relationship between PBS use
      and alcohol-related negative consequences. Participants were 1,782 undergraduate
      students from two West Coast universities who reported past-month incidence of
      heavy episodic drinking (HED). Students reported on their drinking, experience of
      alcohol-related consequences, use of PBS, and depression and anxiety
      symptomatology. Overall, results demonstrated that among participants
      experiencing depression or anxiety, greater PBS utilization was associated with
      significantly lower levels of alcohol-related consequences, even after
      controlling for drinking and other predictors. However, findings also revealed
      important distinctions in the potential effectiveness of PBS by
      depression/anxiety severity and racial-gender subgroup, such that Asian men with
      poor mental health appeared to garner unique and substantial benefit (i.e.,
      lesser consequences) from increased PBS use. Further, PBS were found to offer
      substantial protective benefit for White females, irrespective of mental health.
      This study points to the potential for targeted PBS-specific skills training and
      interventions to minimize alcohol-related risks faced by the growing
      subpopulation of college students experiencing psychological distress, and
      further highlights important race and gender differentials.

PMID- 24079650
TI  - Benefits of migration in a partially-migratory tropical ungulate.
AB  - BACKGROUND: Partial migration, where one portion of a population conducts
      seasonal migrations while the other remains on a single range, is common in wild
      ungulate populations. However the relative costs and benefits associated with the
      distinct strategies adopted by coexisting migrant and resident individuals have
      rarely been investigated. Here we compare the body condition of migrants and
      residents in a partially migratory population of impalas (Aepyceros melampus) in
      Zimbabwe. The study was conducted during two consecutive years with highly
      contrasted population densities (16.4 and 8.6 indiv/km(2)) due to harvesting.
      RESULTS: We first identify a population substructure with a north-south sub
      division in two spatial units related to distinct soils and vegetation cover.
      Impalas in the north range had a consistently higher diet quality and body
      condition than those in the south range. At the beginning of the dry season about
      one third of the individuals migrated from the lower (i.e. south) to the higher
      (i.e. north) diet quality range. This partial migration pattern was consistent
      between the consecutive years, and most individuals showed constancy to their
      moving strategy (migrant or resident). In both years, these migrants had a
      significantly higher body condition at the end of the dry season than the south
      residents that remained year-round in the lower diet quality range. Diet quality
      and body condition of impalas were higher in the year of lower density; however
      we did not detect any evidence for density-dependence in migration propensity, at
      the individual or population levels, nor in the benefit associated with
      migration. CONCLUSIONS: Our findings provide rare evidence for a significant
      relationship between body condition and seasonal migration strategy in wild
      ungulates in relation to a difference in the quality of resources acquired
      between distinct seasonal ranges. This study also constitutes rare evidence of
      partial migration in a tropical ungulate population.

PMID- 24079651
TI  - Using Signal Detection Theory and Time Window-based Human-In-The-Loop simulation
      as a tool for assessing the effectiveness of different qualitative shapes in
      continuous monitoring tasks.
AB  - This paper provides a case study of Signal Detection Theory (SDT) as applied to a
      continuous monitoring dual-task environment. Specifically, SDT was used to
      evaluate the independent contributions of sensitivity and bias to different
      qualitative gauges used in process control. To assess detection performance in
      monitoring the gauges, we developed a Time Window-based Human-In-The-Loop
      (TWHITL) simulation bed. Through this test bed, we were able to generate a
      display similar to those monitored by console operators in oil and gas refinery
      plants. By using SDT and TWHITL, we evaluated the sensitivity, operator bias, and
      response time of flow, level, pressure, and temperature gauge shapes developed by
      Abnormal Situation Management((r)) (ASM((r))) Consortium (www.asmconsortium.org).
      Our findings suggest that display density influences the effectiveness of
      participants in detecting abnormal shapes. Furthermore, results suggest that some
      shapes elicit better detection performance than others. 

PMID- 24079653
TI  - Using videoconferencing to provide psychological services to rural children and
      adolescents: a review and case example.
AB  - Children and adolescents living in rural areas have difficulty accessing
      psychological services due to a lack of psychologists and other behavioral health
      professionals, especially those with expertise in treating youth. Telepsychology
      helps bridge this access gap. This article extends evidence supporting
      videoconferencing for psychological assessment and treatment in adults to support
      telepsychological treatment for youth. In addition, the basic components needed
      to begin and sustain a telepsychological practice are explored. Finally, a case
      example of an adolescent presenting with depression and disordered eating
      illustrates the practice of, and ethical standards needed for, telepsychology.
      Future technologies and applications around telepsychology are also discussed. 

PMID- 24079652
TI  - Engineering folding dynamics from two-state to downhill: application to lambda
      repressor.
AB  - One strategy for reaching the downhill folding regime, primarily exploited for
      the lambda(6-85) protein fragment, consists of cumulatively introducing mutations
      that speed up folding. This is an experimentally demanding process where chemical
      intuition usually serves as a guide for the choice of amino acid residues to
      mutate. Such an approach can be aided by computational methods that screen for
      protein engineering hot spots. Here we present one such method that involves
      sampling the energy landscape of the pseudo-wild-type protein and investigating
      the effect of point mutations on this landscape. Using a novel metric for the
      cooperativity, we identify those residues leading to the least cooperative
      folding. The folding dynamics of the selected mutants are then directly
      characterized and the differences in the kinetics are analyzed within a Markov
      state model framework. Although the method is general, here we present results
      for a coarse-grained topology-based simulation model of lambda-repressor, whose
      barrier is reduced from an initial value of ~4 k(B)T at the midpoint to ~1 k(B)T,
      thereby reaching the downhill folding regime.

PMID- 24079654
TI  - Differential effects of phosphate binders on pre-dialysis serum bicarbonate in
      end-stage kidney disease patients on maintenance haemodialysis.
AB  - BACKGROUND: Phosphate binders' constituents have alkalotic or acidotic properties
      and may contribute to acid base balance in haemodialysis patients. This study
      aimed to investigate the differential effects of phosphate binders on pre
      dialysis serum bicarbonate in End Stage Kidney Disease patients on maintenance
      haemodialysis. METHODS: Stable out-patients having satellite haemodialysis for at
      least 3 months were retrospectively studied for 18 months, excluding those with
      other medical causes for metabolic acidosis. Blood results were censored for
      inpatient episodes, at the time of death, renal transplant or dialysis modality
      change. Multivariable multilevel mixed-effects linear regression was used and
      five groups of phosphate binders were compared: Group A(Calcium (Ca) and/or
      Aluminium (Al) binders); B(Sevelamer hydrochloride (SH) alone); C(lanthanum
      carbonate (LC) alone); D(SH and Ca/Al), E(LC and Ca/Al). RESULTS: Of 320
      patients, 292 were eligible for analysis with a mean follow-up of 15.54 (standard
      deviation, SD 3.98) months. Similar mean pre-dialysis serum levels of bicarbonate
      were observed at all 6 month-interval analyses. At 18(th) months, observed mean
      serum bicarbonate levels in mmol/L were Group B: 21.58 (SD 2.82, P<0.001), C:
      23.29 (SD 2.80, P=0.02), D: 21.56 (SD 3.00, P<0.001), and E: 21.29 (SD 3.62,
      P=0.92) compared with Group A: 22.98 (SD 2.77). Mean serum bicarbonate was
      related to total SH dose in mmol/L: 22.34 (SD 2.56) for SH <2.5 g/day, 21.61 (SD
      2.62) for SH 2.5-4.8 g/day, 21.04 (SD 3.31) for SH >4.8 g/day compared with 22.85
      (SD 2.91) for non-users; P-trend<0.001. CONCLUSIONS: Phosphate binders'
      constituents may contribute to/protect against a predisposition to pre-dialysis
      metabolic acidosis. This may be dose dependant in patients taking Sevelamer
      Hydrochloride.

PMID- 24079655
TI  - Ultrasensitive all-carbon photoelectrochemical bioprobes for zeptomole
      immunosensing of tumor markers by an inexpensive visible laser light.
AB  - A novel enzyme-free and all-carbon photoelectrochemical (PEC) bioprobe, based on
      carboxylated multiwalled carbon nanotube-Congo red-fullerene nanohybrids
      (MWNTCOOH-CR-C60), for the ultrasensitive immunosensing of carcinoembryonic
      antigen (CEA) was reported. The MWNTCOOH-CR-C60 nanohybrids, prepared by
      mechanically grinding a mixture of MWNTCOOH, C60, and CR at a certain mass ratio,
      had good water dispersibility and high PEC conversion efficiency in visible light
      ranges. Covalent binding of the detection antibody of CEA on the MWNTCOOH-CR-C60
      nanohybrids produced a sensitive PEC bioprobe for detection of CEA by sandwich
      immunosensing. The corresponding immunosensor, employing an inexpensive and
      portable green laser light, possessed a wide calibration range of 1.0 pg/mL~100.0
      ng/mL and a low detection limit of 0.1 pg/mL (calculated 5 zmol for a 10.0 MUL
      sample solution) (S/N = 3), which was successfully applied to the detection of
      CEA in serum samples from both healthy people and cancer patients. The present
      work thus demonstrated the promising application of fullerene-based
      nanocomposites in developing highly sensitive, environmentally friendly, and cost
      effective PEC biosensors.

PMID- 24079658
TI  - Very Small Embryonic-Like Stem Cells: Are They Real?

PMID- 24079657
TI  - PINTing for p53.
AB  - A new study identifies the long noncoding RNA Pintas a regulator of cellular
      proliferation and a target of the p53 pathway.

PMID- 24079656
TI  - Positive selection in glycolysis among Australasian stick insects.
AB  - BACKGROUND: The glycolytic pathway is central to cellular energy production.
      Selection on individual enzymes within glycolysis, particularly phosphoglucose
      isomerase (Pgi), has been associated with metabolic performance in numerous
      organisms. Nonetheless, how whole energy-producing pathways evolve to allow
      organisms to thrive in different environments and adopt new lifestyles remains
      little explored. The Lanceocercata radiation of Australasian stick insects
      includes transitions from tropical to temperate climates, lowland to alpine
      habitats, and winged to wingless forms. This permits a broad investigation to
      determine which steps within glycolysis and what sites within enzymes are the
      targets of positive selection. To address these questions we obtained transcript
      sequences from seven core glycolysis enzymes, including two Pgi paralogues, from
      29 Lanceocercata species. RESULTS: Using maximum likelihood methods a signature
      of positive selection was inferred in two core glycolysis enzymes. Pgi and
      Glyceraldehyde 3-phosphate dehydrogenase (Gaphd) genes both encode enzymes
      linking glycolysis to the pentose phosphate pathway. Positive selection among Pgi
      paralogues and orthologues predominately targets amino acids with residues
      exposed to the protein's surface, where changes in physical properties may alter
      enzyme performance. CONCLUSION: Our results suggest that, for Lancerocercata
      stick insects, adaptation to new stressful lifestyles requires a balance between
      maintaining cellular energy production, efficiently exploiting different energy
      storage pools and compensating for stress-induced oxidative damage.

PMID- 24079659
TI  - The origin of relative intensity fluctuations in single-molecule tip-enhanced
      Raman spectroscopy.
AB  - An explanation of the relative intensity fluctuations observed in single-molecule
      Raman experiments is described utilizing both single-molecule tip-enhanced Raman
      spectroscopy and time-dependent density functional theory calculations. No
      correlation is observed in mode to mode intensity fluctuations indicating that
      the changes in mode intensities are completely independent. Theoretical
      calculations provide convincing evidence that the fluctuations are not the result
      of diffusion, orientation, or local electromagnetic field gradients but rather
      are the result of subtle variations of the excited-state lifetime, energy, and
      geometry of the molecule. These variations in the excited-state properties will
      provide information on adsorbate-adsorbate and adsorbate-substrate interactions
      and may allow for inversion of experimental results to obtain these excited-state
      properties. 

PMID- 24079661
TI  - Inhibitors of cathepsin G: a patent review (2005 to present).
AB  - INTRODUCTION: Cathepsin G (CatG) is a neutral proteinase originating from human
      neutrophils. It displays a unique dual specificity (trypsin- and chymotrypsin
      like); thus, its enzymatic activity is difficult to control. CatG is involved in
      the pathophysiology of several serious human diseases, such as chronic
      obstructive pulmonary disease (COPD), Crohn's disease, rheumatoid arthritis,
      cystic fibrosis and other conditions clinically manifested by excessive
      inflammatory reactions. For mentioned reasons, CatG was considered as good
      molecular target for the development of novel drugs. However, none of them have
      yet entered the market as novel therapeutic agents. AREAS COVERED: This article
      presents an in-depth and detailed analysis of the therapeutic potential of CatG
      inhibitors based on a review of patent applications and academic publishing
      disclosed in patents and patent applications (1991 - 2012), with several
      exceptions for inhibitors retrieved from academic articles. EXPERT OPINION: Among
      the discussed inhibitors of CatG, examples corresponding to derivatives of beta
      ketophosphonic acids, aminoalkylphosphonic esters and boswellic acids (BAs) could
      be regarded as the most promising. The most promising one seems to be analogues
      of compounds of Nature's origin (peptidic and BA derivates). Nevertheless,
      nothing is currently known about the clinical disposition of any of the CatG
      inhibitors discovered so far. This latter point suggests that there is still a
      lot of work to do in the design of stable, pharmacologically active compounds
      able to specifically regulate the in vivo activity of cathepsin G.

PMID- 24079660
TI  - Human Polyomavirus JC monitoring and noncoding control region analysis in dynamic
      cohorts of individuals affected by immune-mediated diseases under treatment with
      biologics: an observational study.
AB  - BACKGROUND: Progressive multifocal leukoencephalopathy (PML) onset, caused by
      Polyomavirus JC (JCPyV) in patients affected by immune-mediated diseases during
      biological treatment, raised concerns about the safety profile of these agents.
      Therefore, the aims of this study were the JCPyV reactivation monitoring and the
      noncoding control region (NCCR) and viral protein 1 (VP1) analysis in patients
      affected by different immune-mediated diseases and treated with biologics.
      METHODS: We performed JCPyV-specific quantitative PCR of biological samples
      collected at moment of recruitment (t0) and every 4 months (t1, t2, t3, t4).
      Subsequently, rearrangements' analysis of NCCR and VP1 was carried out. Data were
      analyzed using chi2 test. RESULTS: Results showed that at t0 patients with
      chronic inflammatory rheumatic diseases presented a JCPyV load in the urine
      significantly higher (p<=0.05) than in patients with multiple sclerosis (MS) and
      Crohn's disease (CD). It can also be observed a significant association between
      JC viruria and JCPyV antibodies after 1 year of natalizumab (p=0.04) in MS
      patients. Finally, NCCR analysis showed the presence of an archetype-like
      sequence in all urine samples, whereas a rearranged NCCR Type IR was found in
      colon-rectal biopsies collected from 2 CD patients after 16 months of infliximab.
      Furthermore, sequences isolated from peripheral blood mononuclear cells (PBMCs)
      of 2 MS patients with JCPyV antibody at t0 and t3, showed a NCCR Type IIR with a
      duplication of a 98 bp unit and a 66 bp insert, resulting in a boxB deletion and
      37 T to G transversion into the Spi-B binding site. In all patients, a prevalence
      of genotypes 1A and 1B, the predominant JCPyV genotypes in Europe, was observed.
      CONCLUSIONS: It has been important to understand whether the specific
      inflammatory scenario in different immune-mediated diseases could affect JCPyV
      reactivation from latency, in particular from kidneys. Moreover, for a more
      accurate PML risk stratification, testing JC viruria seems to be useful to
      identify patients who harbor JCPyV but with an undetectable JCPyV-specific
      humoral immune response. In these patients, it may also be important to study the
      JCPyV NCCR rearrangement: in particular, Spi-B expression in PBMCs could play a
      crucial role in JCPyV replication and NCCR rearrangement.

PMID- 24079662
TI  - Rational development of 4-aminopyridyl-based inhibitors targeting Trypanosoma
      cruzi CYP51 as anti-chagas agents.
AB  - A new series of 4-aminopyridyl-based lead inhibitors targeting Trypanosoma cruzi
      CYP51 (TcCYP51) has been developed using structure-based drug design as well as
      structure-property relationship (SPR) analyses. The screening hit starting point,
      LP10 (KD <= 42 nM; EC50 = 0.65 MUM), has been optimized to give the potential
      leads 14t, 27i, 27q, 27r, and 27t, which have low-nanomolar binding affinity to
      TcCYP51 and significant activity against T. cruzi amastigotes cultured in human
      myoblasts (EC50 = 14-18 nM for 27i and 27r). Many of the optimized compounds have
      improved microsome stability, and most are selective against human CYPs 1A2, 2D6,
      and 3A4 (<50% inhibition at 1 MUM). A rationale for the improvement in microsome
      stability and selectivity of inhibitors against human metabolic CYP enzymes is
      presented. In addition, the binding mode of 14t with the Trypanosoma brucei CYP51
      (TbCYP51) orthologue has been characterized by X-ray structure analysis. 

PMID- 24079663
TI  - A case of acute myeloid leukemia (AML) with an unreported combination of
      chromosomal abnormalities: gain of isochromosome 5p, tetrasomy 8 and unbalanced
      translocation der(19)t(17;19)(q23;p13).
AB  - BACKGROUND: Acute myeloid leukemia (AML) comprises a spectrum of myeloid
      malignancies which are often associated with distinct chromosomal abnormalities,
      and the analysis of such abnormalities provides us with important information for
      disease classification, treatment selection and prognosis. Some chromosomal
      abnormalities albeit recurrent are rare such as tetrasomy 8 or isochromosome 5p.
      In addition, erratic chromosomal rearrangements may occur in AML, sometimes
      unbalanced and also accompanied by other abnormalities. Knowledge on the
      contribution of rare abnormalities to AML disease, progression and prognosis is
      limited.Here we report a unique case of acute monoblastic leukemia with gain of
      i(5)(p10), tetrasomy 8, an unbalanced translocation der(19)t(17;19)(q23;p13.3)
      and mutated NPM1. RESULTS: Bone marrow cells were examined by conventional
      karyotyping, fluorescence in situ hybridization (FISH) and mutation analysis at
      diagnosis and follow-up. At diagnosis we detected trisomy 8, an unbalanced
      translocation der(19)t(17;19)(q23;p13.3) and mutated NPM1. During the course of
      the disease we observed clonal evolution with gain of i(5)(p10), tetrasomy 8 and
      eventually duplication of der(19)t(17;19)(q23;p13.3). By using the
      der(19)t(17;19) as clonal marker, we found that i(5)(p10) and tetrasomy 8 were
      secondary genetic events and that tetrasomy 8 had clonally evolved from trisomy
      8. CONCLUSIONS: This case of acute monoblastic leukemia presents a combination of
      rare chromosomal abnormalities including the unbalanced translocation
      der(19)t(17;19)(q23;p13.3), hitherto un-reported in AML. In addition, our case
      supports the hypothesis of a step-wise clonal evolution from trisomy 8 to
      tetrasomy 8 in AML. Reporting and collecting data of rare chromosomal
      abnormalities will add information to AML disease, progression and prognosis, and
      may eventually translate to improved patient management.

PMID- 24079664
TI  - Total synthesis of epothilone D: the nerol/macroaldolization approach.
AB  - A highly convergent and stereocontrolled synthesis of epothilone D (4) is
      reported. Key features are a cheap and Z-selective synthesis of the northern half
      based on nerol and acetoacetate and chromium(II)-mediated Reformatsky reactions
      as a powerful tool for chemoselective asymmetric carbon-carbon bond formations,
      including an unusual stereospecific macroaldolization. 

PMID- 24079665
TI  - Evaluation and management of nonaccidental head trauma.

PMID- 24079666
TI  - Basketball competition. . .followed by blurred vision.

PMID- 24079667
TI  - Risk factors for consecutive exotropia.

PMID- 24079668
TI  - Ophthalmic migraine with pupil-sparing third nerve palsy.

PMID- 24079669
TI  - Characterization of a water-solid interaction in a partially ordered system.
AB  - GNE068-PC, a developmental compound, was previously characterized to be
      mesomorphous, i.e. having long-range order associated with significant local
      molecular disorder (Chakravarty et. al., Mol. Pharmaceutics, accepted). The
      compound was exposed to moisture under different relative humidity conditions
      ranging from 11% to 60% RH at room temperature (RT) for 7 days, and the resultant
      product phases were characterized. The partially ordered sample progressively
      lost crystallinity (long-range order) and birefringence (orientational order)
      upon exposure to increasing RH conditions, leading to the formation of a
      completely disordered amorphous phase at 60% RH (RT). Long-range positional order
      was irrecoverable even after moisture removal from the sample exposed to 60% RH.
      This was attributed to replacement of residual ethyl acetate by water, the former
      being critical for maintenance of long-range order in the material. In addition,
      water sorption appeared to irreversibly alter the molecular orientation, thereby
      affecting sample birefringence. Solid-state NMR revealed increases in (1)H and
      (13)C spin-lattice relaxation times (T1) going from the mesomorphous phase to the
      fully amorphous phase. This was indicative of reduction in lattice mobility,
      likely due to the decreased motion of the aromatic portions of the molecule, in
      particular C17, which showed the most dramatic increase in (13)C T1. This is
      likely due to decrease in available free volume upon water sorption. Drying of
      the hydrated disordered phase showed somewhat greater mobility than the hydrated
      phase, likely due to increased relative free volume through removal of water. A
      water-solid interaction therefore irreversibly changed the solid-state makeup of
      GNE068-PC. 

PMID- 24079670
TI  - Differential validity for cognitive ability tests in employment and educational
      settings: not much more than range restriction?
AB  - The concept of differential validity suggests that cognitive ability tests are
      associated with varying levels of validity across ethnic groups, such that
      validity is lower in certain ethnic subgroups than in others. A recent meta
      analysis has revived the viability of this concept. Unfortunately, data were not
      available in this meta-analysis to correct for range restriction within ethnic
      groups. We reviewed the differential validity literature and conducted 4 studies.
      In Study 1, we empirically demonstrated that using a cognitive ability test with
      a common cutoff decreases variance in test scores of Black subgroup samples more
      than in White samples. In Study 2, we developed a simulation that examined the
      effects of range restriction on estimates of differential validity. Results
      demonstrated that different levels of range restriction for subgroups can explain
      the apparent observed differential validity results in employment and educational
      settings (but not military settings) when no differential validity exists in the
      population. In Study 3, we conducted a simulation in which we examined how one
      corrects for range restriction affects the accuracy of these corrections. Results
      suggest that the correction approach using a common range restriction ratio for
      various subgroups may create or perpetuate the illusion of differential validity
      and that corrections are most accurate when done within each subgroup. Finally,
      in Study 4, we conducted a simulation in which we assumed differential validity
      in the population. We found that range restriction artificially increased the
      size of observed differential validity estimates when the validity of cognitive
      ability tests was assumed to be higher among Whites. Overall, we suggest that the
      concept of differential validity may be largely artifactual and current data are
      not definitive enough to suggest such effects exist.

PMID- 24079671
TI  - Family incivility and job performance: a moderated mediation model of
      psychological distress and core self-evaluation.
AB  - This study extends the stress literature by exploring the relationship between
      family incivility and job performance. We examine whether psychological distress
      mediates the link between family incivility and job performance. We also
      investigate how core self-evaluation might moderate this mediated relationship.
      Data from a 2-wave study indicate that psychological distress mediates the
      relationship between family incivility and job performance. In addition, core
      self-evaluation moderates the relationship between family incivility and
      psychological distress but not the relationship between psychological distress
      and job performance. The results hold while controlling for general job stress,
      family-to-work conflict, and work-to-family conflict. The findings suggest that
      family incivility is linked to poor performance at work, and psychological
      distress and core self-evaluation are key mechanisms in the relationship.

PMID- 24079672
TI  - Buffering the negative effects of employee surface acting: the moderating role of
      employee-customer relationship strength and personalized services.
AB  - The impact of emotional labor on customer outcomes is gaining considerable
      attention in the literature, with research suggesting that the authenticity of
      emotional displays may positively impact customer outcomes. However, research
      investigating the impact of more inauthentic emotions on service delivery
      outcomes is mixed (see Chi, Grandey, Diamond, & Krimmel, 2011). This study
      explores 2 potential reasons for why the service outcomes of inauthentic emotions
      are largely inconsistent: the impact of distinct surface acting strategies and
      the role of service delivery context. Drawing on social-functional theories of
      emotions, we surveyed 243 dyads of employees and customers from a wide variety of
      services to examine the links between employee surface acting and customer
      service satisfaction, and whether this relationship is moderated by relationship
      strength and service personalization. Our findings suggest that faking positive
      emotions has no bearing on service satisfaction, but suppressing negative
      emotions interacts with contextual factors to predict customers' service
      satisfaction, in line with social-functional theories of emotions. Specifically,
      customers who know the employee well are less sensitive to the negative effects
      of suppressed negative emotions, and customers in highly personalized service
      encounters are more sensitive to the negative effects of suppressed negative
      emotions. We conclude with a discussion of theoretical and practical
      implications.

PMID- 24079673
TI  - VRK2 identifies a subgroup of primary high-grade astrocytomas with a better
      prognosis.
AB  - BACKGROUND: Malignant astrocytomas are the most common primary brain tumors and
      one of the most lethal among human cancers despite optimal treatment. Therefore,
      the characterization of molecular alterations underlying the aggressive behavior
      of these tumors and the identification of new markers are thus an important step
      towards a better patient stratification and management. METHODS AND RESULTS: VRK1
      and VRK2 (Vaccinia-related kinase-1, -2) expression, as well as proliferation
      markers, were determined in a tissue microarray containing 105 primary
      astrocytoma biopsies. Kaplan Meier and Cox models were used to find clinical
      and/or molecular parameters related to overall survival. The effects of VRK
      protein levels on proliferation were determined in astrocytoma cell lines. High
      levels of both protein kinases, VRK1 or VRK2, correlated with proliferation
      markers, p63 or ki67. There was no correlation with p53, reflecting the
      disruption of the VRK-p53-DRAM autoregulatory loop as a consequence of p53
      mutations. High VRK2 protein levels identified a subgroup of astrocytomas that
      had a significant improvement in survival. The potential effect of VRK2 was
      studied by analyzing the growth characteristics of astrocytoma cell lines with
      different EGFR/VRK2 protein ratios. CONCLUSION: High levels of VRK2 resulted in a
      lower growth rate suggesting these cells are more indolent. In high-grade
      astrocytomas, VRK2 expression constitutes a good prognostic marker for patient
      survival.

PMID- 24079674
TI  - The quest to prove endovascular stroke therapy: searching for the "sweet spot" in
      patient selection.

PMID- 24079675
TI  - Empiricism and rationalism in medicine: can 2 competing philosophies coexist to
      improve the quality of medical care?

PMID- 24079676
TI  - Why randomized controlled trials are needed to accept new practices: 2 medical
      worldviews.

PMID- 24079677
TI  - Endovascular therapy for acute ischemic stroke: a systematic review and meta
      analysis.
AB  - OBJECTIVE: To consolidate the evidence from randomized trials for the use of
      endovascular therapy (ET) in patients with acute ischemic stroke. METHODS: We
      searched major databases (MEDLINE, EMBASE, Cochrane Central Register of
      Controlled Trials, Cochrane Database of Systematic Reviews, and Scopus) from
      their inception to February 12, 2013, for randomized trials evaluating the
      efficacy of ET compared with standard of care for acute ischemic stroke. Pooled
      absolute and relative risk estimates were synthesized by using a random-effects
      model. Heterogeneity was assessed by using Q statistic and I(2) statistic. Subset
      analysis was performed for patients with severe stroke (National Institutes of
      Health Stroke Scale score >=20). The study was conducted from January 15, 2013 to
      April 30, 2013. RESULTS: Of the 1252 retrieved articles, 5 randomized trials
      enrolling 1197 patients with acute ischemic stroke were included. Seven hundred
      eleven patients received ET, and 486 received intravenous (IV) tissue plasminogen
      activator. There was no significant improvement in any of the outcomes in
      patients receiving ET compared with those receiving IV thrombolysis. On subgroup
      analysis, ET was found to have better outcomes in patients with severe stroke
      (National Institutes of Health Stroke Scale score >=20), showing a dose-response
      gradient and improving excellent, good, and fair outcomes by an additional 4%,
      7%, and 13%, respectively, compared with IV thrombolysis. CONCLUSION: Overall, ET
      is not superior to IV thrombolysis for acute ischemic strokes (level B
      recommendation). However, ET showed promise and improved outcomes in patients
      with severe strokes, but the evidence is limited due to sample size. There is a
      need for further trials evaluating the role of ET in this high-risk group.

PMID- 24079678
TI  - Improving affordability through innovation in the surgical treatment of mitral
      valve disease.
AB  - OBJECTIVE: To determine whether technically innovative cardiac surgical platforms
      (ie, robotics) deployed in conjunction with surgical process improvement (systems
      innovation) influence total hospital costs to address the concern that expanding
      adoption might increase health care expenses. PATIENTS AND METHODS: We studied
      185 propensity-matched patient pairs (370 patients) undergoing isolated
      conventional open vs robotic mitral valve repair with identical repair techniques
      and care teams between July 1, 2007, and January 31, 2011. Two time periods were
      considered, before the implementation of system innovations (pre-July 2009) and
      after implementation. Generalized linear mixed models were used to estimate the
      effect of the type of surgery on cost while adjusting for a time effect. RESULTS:
      Baseline characteristics of the study patients were similar, and all patients
      underwent successful mitral valve repair with no early deaths. Median length of
      stay (LOS) for patients undergoing open repair was unchanged at 5.3 days (P=.636)
      before and after systems innovation implementation, and was lower for robotic
      patients at 3.5 and 3.4 days, respectively (P=.003), throughout the study. The
      overall median costs associated with open and robotic repair were $31,838 and
      $32,144, respectively (P=.32). During the preimplementation period, the total
      cost was higher for robotic ($34,920) than for open ($32,650) repair (P<.001),
      but during the postimplementation period, the median cost of robotic repair
      ($30,606) became similar to that of open repair ($31,310) (P=.876). The largest
      decrease in robotic cost was associated with more rapid ventilator weaning and
      shortened median intensive care unit LOS, from 22.7 hours before July 2009 to 9.3
      hours after implementation of systems innovations (P<.001). CONCLUSION: Following
      the introduction of systems innovation, the total hospital cost associated with
      robotic mitral valve repair has become similar to that for a conventional open
      approach, while facilitating quicker patient recovery and diminished utilization
      of in-hospital resources. These data suggest that innovations in techniques
      (robotics) along with care systems (process improvement) can be cost-neutral,
      thereby improving the affordability of new technologies capable of improving
      early patient outcomes.

PMID- 24079680
TI  - The necessity for clinical reasoning in the era of evidence-based medicine.
AB  - Clinical decisions are increasingly driven by evidence-based recommendations of
      guideline groups, which aim to be based on the highest quality knowledge
      randomized clinical trials (RCTs) and meta-analyses. Although RCTs provide the
      best assessment of the overall value of a therapy, high-quality evidence from
      RCTs is often incomplete, contradictory, or absent even in areas that have been
      most exhaustively studied. Moreover, the likelihood of the success or failure of
      a therapy is not identical in all the individuals treated in any trial because
      therapy is not the only determinant of outcome. Therefore, the overall results of
      a trial cannot be assumed to apply to any particular individual, not even someone
      who corresponds to all the entry criteria for the trial. In addition, the
      potential for bias due to financial conflicts remains in many guideline groups.
      Guidelines are key sources of knowledge. Nevertheless, limitations in the extent,
      quality, generalizability, and transferability of evidence mean that we
      clinicians must still reason through the best choices for an individual because
      even in the absence of full and secure knowledge, clinical decisions must still
      be made. Clinical reasoning is the pragmatic, tried-and-true process of expert
      clinical problem solving that does value mechanistic reasoning and clinical
      experience as well as RCTs and observational studies. Clinicians must continue to
      value clinical reasoning if our aim is the best clinical care for all the
      individuals we treat. 

PMID- 24079681
TI  - Chronic cough: an update.
AB  - Cough persisting beyond 8 weeks (ie, chronic cough) is one of the most common
      reasons for an outpatient visit. A protracted cough can negatively affect one's
      quality of life by causing anxiety, physical discomfort, social isolation, and
      personal embarrassment. Herein, the anatomy and physiology of the cough reflex
      are reviewed. Upper airway cough syndrome, asthma, eosinophilic bronchitis, and
      gastroesophageal reflux disease account for most chronic cough after excluding
      smoking, angiotensin-converting enzyme inhibitor use, and chronic bronchitis.
      Many patients have more than one reason for chronic cough. Treating the
      underlying cause(s) resolves cough in most instances. There are some coughs that
      seem refractory despite an extensive work-up. The possibility of a hypersensitive
      cough reflex response has been proposed to explain these cases. Several clinical
      algorithms to evaluate chronic cough are presented. 

PMID- 24079679
TI  - Characteristics of resistant hypertension in a large, ethnically diverse
      hypertension population of an integrated health system.
AB  - OBJECTIVE: To evaluate the prevalence of and characterize resistant hypertension
      in a large representative population with successful hypertension management and
      reliable health information. PATIENT AND METHODS: We performed a cross-sectional
      study using clinical encounter, laboratory, and administrative information from
      the Kaiser Permanente Southern California health system between January 1, 2006,
      and December 31, 2007. From individuals older than 17 years with hypertension,
      resistant hypertension was identified and prevalence was determined.
      Multivariable logistic regression was used to calculate odds ratios (ORs), with
      adjustments for demographic characteristics, clinical variables, and medication
      use. RESULTS: Of 470,386 hypertensive individuals, 60,327 (12.8%) were identified
      as having resistant disease, representing 15.3% of those taking medications.
      Overall, 37,061 patients (7.9%) had uncontrolled hypertension while taking 3 or
      more medicines. The ORs (95% CIs) for resistant hypertension were greater for
      black race (1.68 [1.62-1.75]), older age (1.11 [1.10-1.11] for every 5-year
      increase), male sex (1.06 [1.03-1.10]), and obesity (1.46 [1.42-1.51]).
      Medication adherence rates were higher in those with resistant hypertension (93%
      vs 89.8%; P<.001). Chronic kidney disease (OR, 1.84; 95% CI, 1.78-1.90), diabetes
      mellitus (OR, 1.58; 95% CI, 1.53-1.63), and cardiovascular disease (OR, 1.34; 95%
      CI, 1.30-1.39) were also associated with higher risk of resistant hypertension.
      CONCLUSION: In a more standardized hypertension treatment environment, we
      observed a rate of resistant hypertension comparable with that of previous
      studies using more fragmented data sources. Past observations have been limited
      due to nonrepresentative populations, reliability of the data, heterogeneity of
      the treatment environments, and less than ideal control rates. This cohort, which
      was established using an electronic medical record-based approach, has the
      potential to provide a better understanding of resistant hypertension and
      outcomes.

PMID- 24079683
TI  - Acupuncture.
AB  - Worldwide, acupuncture is integral to everyday medical practice. In recent
      decades its practice has gained popularity in the United States. With increasing
      evidence of its clinical efficacy, acupuncture is now a widely practiced
      treatment modality in complementary and integrative medicine. According to the
      2007 National Health Interview Survey, an estimated 3.1 million US adults and
      150,000 children had acupuncture in the previous year. The National Health
      Interview Survey also estimated that between 2002 and 2007, acupuncture use among
      adults increased by approximately 1 million people. Patients want more
      information from their clinicians about the use of acupuncture and its safety and
      efficacy. Although many clinicians may recommend acupuncture, they often believe
      they are not sufficiently informed to discuss acupuncture with their patients.
      This article provides answers to the most frequently asked questions regarding
      acupuncture. 

PMID- 24079684
TI  - 31-year-old woman with alopecia.

PMID- 24079685
TI  - Whole organ and tissue reconstruction in thoracic regenerative surgery.
AB  - Development of novel prognostic, diagnostic, and treatment options will provide
      major benefits for millions of patients with acute or chronic respiratory
      dysfunction, cardiac-related disorders, esophageal problems, or other diseases in
      the thorax. Allogeneic organ transplant is currently available. However, it
      remains a trap because of its dependency on a very limited supply of donated
      organs, which may be needed for both initial and subsequent transplants.
      Furthermore, it requires lifelong treatment with immunosuppressants, which are
      associated with adverse effects. Despite early clinical applications of
      bioengineered organs and tissues, routine implementation is still far off. For
      this review, we searched the PubMed, MEDLINE, and Ovid databases for the
      following keywords for each tissue or organ: tissue engineering, biological and
      synthetic scaffold/graft, acellular and decelluar(ized), reseeding, bioreactor,
      tissue replacement, and transplantation. We identified the current state-of-the
      art practices in tissue engineering with a focus on advances during the past 5
      years. We discuss advantages and disadvantages of biological and synthetic
      solutions and introduce novel strategies and technologies for the field. The
      ethical challenges of innovation in this area are also reviewed. 

PMID- 24079682
TI  - Etiology and therapeutic approach to elevated lactate levels.
AB  - Lactate levels are commonly evaluated in acutely ill patients. Although most
      often used in the context of evaluating shock, lactate levels can be elevated for
      many reasons. While tissue hypoperfusion may be the most common cause of
      elevation, many other etiologies or contributing factors exist. Clinicians need
      to be aware of the many potential causes of lactate level elevation as the
      clinical and prognostic importance of an elevated lactate level varies widely by
      disease state. Moreover, specific therapy may need to be tailored to the
      underlying cause of elevation. The present review is based on a comprehensive
      PubMed search between the dates of January 1, 1960, to April 30, 2013, using the
      search term lactate or lactic acidosis combined with known associations, such as
      shock, sepsis, cardiac arrest, trauma, seizure, ischemia, diabetic ketoacidosis,
      thiamine, malignancy, liver, toxins, overdose, and medication. We provide an
      overview of the pathogenesis of lactate level elevation followed by an in-depth
      look at the varied etiologies, including medication-related causes. The strengths
      and weaknesses of lactate as a diagnostic/prognostic tool and its potential use
      as a clinical end point of resuscitation are discussed. The review ends with some
      general recommendations on the management of patients with elevated lactate
      levels. 

PMID- 24079686
TI  - Electrical storm in the brain and in the heart: epilepsy and Brugada syndrome.
AB  - We describe a patient with the coincidence of 2 ion channel disorders with
      autosomal dominant inheritance: Brugada syndrome, a potentially fatal cardiac
      condition, and cryptogenic focal epilepsy, likely due to a neurologic
      channelopathy. Although Brugada syndrome was discovered incidentally, most of the
      clinical features of epilepsy in this patient shared the risk factor
      characteristics of sudden unexplained death in epilepsy syndrome. This case
      provides additional information on the potential interaction between ion channel
      abnormalities in the heart and in the brain. Furthermore, it may suggest that
      patients with epilepsy at increased risk for sudden unexplained death in epilepsy
      syndrome should undergo a careful cardiac evaluation. 

PMID- 24079687
TI  - Antineutrophil cytoplasmic antibody-associated renal vasculitis treated with
      autologous mesenchymal stromal cells: evaluation of the contribution of immune
      mediated mechanisms.
AB  - We report the first case of renal antineutrophil cytoplasmic antibody (ANCA)
      associated vasculitis treated with autologous mesenchymal stromal cells (MSCs). A
      73-year-old man was admitted to the hospital for malaise, weight loss, and
      oliguria. His serum creatinine level was 2.7 mg/dL but it rapidly increased to
      7.8 mg/dL; urinalysis showed proteinuria and hematuria, and the ANCA to
      myeloperoxidase with a perinuclear pattern (pANCA) titer was high (132 IU/mL).
      Renal biopsy showed necrotizing crescentic glomerulonephritis. Standard
      immunosuppressive therapy (cyclophosphamide and corticosteroids) was ineffective.
      Rituximab therapy was started, but it was discontinued after the third dose to
      minimize the risk of systemic spread of a severe oral Candida infection and to
      prevent superinfections that were facilitated by leukopenia. The patient received
      autologous MSCs, 1.5 * 10(6) cells/kg body weight, intravenously. After 7 days,
      his serum creatinine level decreased to 2.2 mg/dL, pANCA titer decreased to 75
      IU/mL, and urinalysis findings normalized. Eight months later, he received a
      second MSC infusion because his serum creatinine level increased. In 1 week, his
      creatinine level decreased to 1.9 mg/dL and his pANCA titer decreased to 14
      IU/mL. Immunosuppressive therapy was subsequently withdrawn. At the last follow
      up visit, 12 months after the second MSC infusion, the patient remained in
      clinical remission without any therapy. Infusion of MSCs induced expansion of the
      T-lymphocyte subset expressing a regulatory T-cell phenotype
      (CD4(+)CD25(+)Foxp3(+)) and a notable reduction in interferon-gamma, interleukin
      6, and tumor necrosis factor serum levels. 

PMID- 24079688
TI  - Consider the personhood of women who experienced genital cutting.

PMID- 24079689
TI  - In reply-consider the personhood of women who experienced genital cutting.

PMID- 24079691
TI  - Reversal of medical practices.

PMID- 24079690
TI  - Trends in pneumonia hospitalizations in Hennepin County, Minnesota, 1999-2010.

PMID- 24079692
TI  - In reply I-reversal of medical practices.

PMID- 24079693
TI  - In reply II-reversal of medical practices.

PMID- 24079694
TI  - 83-year-old man with abdominal swelling and lower extremity edema.

PMID- 24079695
TI  - Michael Servetus: unorthodox theologian, meticulous cartographer, and innovative
      anatomist.

PMID- 24079697
TI  - Disseminated histoplasmosis: a cause of hemophagocytic syndrome.

PMID- 24079698
TI  - Waardenburg syndrome.

PMID- 24079699
TI  - The emergence of maternal health as a political priority in Madhya Pradesh,
      India: a qualitative study.
AB  - BACKGROUND: Politics plays a critical role in agenda setting in health affairs;
      therefore, understanding the priorities of the political agenda in health is very
      important. The political priority for safe motherhood has been investigated at
      the national level in different countries. The objective of this study was to
      explore why and how maternal health became a political priority at sub-national
      level in the state of Madhya Pradesh in India. METHODS: This study followed a
      qualitative design. Data were collected by carrying out interviews and review of
      documents. Semi-structured interviews were carried out with twenty respondents
      from four stakeholder groups: government officials, development partners, civil
      society and academics. Data analysis was performed using thematic analysis. The
      analysis was guided by Kingdon's multiple streams model. RESULTS: The emergence
      of maternal health as a political priority in Madhya Pradesh was the result of
      convergence in the developments in different streams: the development of problem
      definition, policy generation and political change. The factors which influenced
      this process were: emerging evidence of the high magnitude of maternal mortality,
      civil society's positioning of maternal mortality as a human rights violation,
      increasing media coverage, supportive policy environment and launch of the
      National Rural Health Mission (NRHM), the availability of effective policy
      solutions, India's aspiration of global leadership, international influence,
      maternal mortality becoming a hot debate topic and political transition at the
      national and state levels. Most of these factors first became important at
      national level which then cascaded to the state level. Currently, there is a
      supportive policy environment in the state for maternal health backed by greater
      political will and increased resources. However, malnutrition and population
      stabilization are the competing priorities which may push maternal health off the
      agenda. CONCLUSIONS: The influence of the events and factors evolving from
      international and national levels significantly contributed to the development of
      maternal health as a priority in Madhya Pradesh. This led to several
      opportunities in terms of policies, guidelines and programmes for improving
      maternal health. These efforts were successful to some extent in improving
      maternal health in the state but several implementation challenges still require
      special attention.

PMID- 24079700
TI  - In vitro and in vivo inhibitory effects of some fungicides on catalase produced
      and purified from white-rot fungus Phanerochaete chrysosporium.
AB  - In this study, in vitro and in vivo effects of some commonly used fungicides,
      antibiotics, and various chemicals on isolated and purified catalase from
      Phanerochaete chrysosporium were investigated. The catalase was purified 129.10
      fold by using 60% ammonium sulfate and 60% ethanol precipitations, DEAE-cellulose
      anion exchange and Sephacryl-S-200 gel filtration chromatographies from P.
      chrysosporium growth in carbon- and nitrogen-limited medium for 12 days. The
      molecular weight of native purified catalase from P. chrysosporium was found to
      be 290 +/- 10 kDa, and sodium dodecyl sulfate (SDS)-PAGE results indicated that
      enzyme consisted of four apparently identical subunits, with a molecular weight
      of 72.5 +/- 2.5 kDa. Kinetic characterization studies showed that optimum pH and
      temperature, Km and Vmax values of the purified catalase which were stable in
      basic region and at comparatively high temperatures were 7.5, 30 degrees C,
      289.86 mM, and 250,000 U/mg, respectively. The activity of purified catalase from
      P. chrysosporium was significantly inhibited by dithiothreitol (DTT), 2
      mercaptoethanol, iodoacetamide, EDTA, and sodium dodecyl sulfate (SDS). It was
      found that while antibiotics had no inhibitory effects, 45 ppm benomyl, 144 ppm
      captan, and 47.5 ppm chlorothalonil caused 14.52, 10.82, and 38.86% inhibition of
      purified catalase, respectively. The inhibition types of these three fungicides
      were found to be non-competitive inhibition with the Ki values of 1.158, 0.638,
      and 0.145 mM and IC50 values of 0.573, 0.158, 0.010 mM, respectively. The results
      of in vivo experiments also showed that benomyl, captan and chlorothalonil caused
      15.25, 1.96, and 36.70% activity decreases after 24-h treatments compared to that
      of the control.

PMID- 24079701
TI  - Development and characterization of nanocarriers for topical treatment of
      psoriasis by using combination therapy.
AB  - Psoriasis is an autoimmune, chronic, inflammatory skin disease characterized by
      epidermal hyperplasia, proliferation of blood vessels, and infiltration of
      leukocytes in dermis and epidermis. Several immunosuppressants such as
      methotrexate (MXT) and cyclosporine are used but they are associated with adverse
      effects due to down regulation of immune system. Numerous approaches have been
      explored to overcome the problems of conventional topical system such as high
      frequency of application, impermeability to skin barrier, and limited efficacy.
      Photodynamic therapy is another non-invasive technique currently used for skin
      diseases. The combination of two drugs is also commonly observed to achieve more
      effective therapy. In the present study, antipsoriatic activity of niosomal
      formulations for the treatment of psoriasis in combination with narrow and broad
      band UV radiation had been explored in experimental animal model.

PMID- 24079702
TI  - Runaway transcription.
AB  - A newly demonstrated defect in RNA polymerase II termination caused by 7SK snRNA
      knockdown may have revealed a novel mechanism uncoupling RNA processing from
      transcription.

PMID- 24079703
TI  - Analysis of compounds that interfere with herpes simplex virus-host receptor
      interactions using surface plasmon resonance.
AB  - The entry of herpes simplex virus into host cells involves a complex series of
      events that require concerted inputs from multiple HSV glycoproteins. Among these
      glycoproteins, the gD protein of HSV-1 and HSV-2 plays an important role for host
      receptor binding and membrane fusion. In the present study, we evaluated the
      ability of different sulfated saccharides to interfere with gD-host receptor
      (HVEM) interactions using our recently reported molecular assay (Gopinath, S. C.
      B.; Hayashi, K.; Kumar, P. K. R. J. Virol. 2012, 86, 6732-6744). Initially, we
      tested the ability of heparan sulfate to interfere with the HVEM-HSV-1 gD
      interaction and found that heparan sulfate is able to interfere efficiently, with
      an apparent EC50 of 2.1 MUM. In addition, we tested different synthetic sulfated
      polysaccharides and natural sulfated polysaccharides from an edible alga,
      Sargassum horneri , after fractionation into different sizes and sulfate and
      uronic acid contents. Six polysaccharides isolated from S. horneri were found to
      efficiently interfere with the HVEM-gD interaction. Three others caused moderate
      interference, and five caused weak interference. These results were confirmed
      with plaque assays, and good agreement was found with the results of the SPR
      assay for the identification of compounds that interfere with HVEM-HSV-1 gD
      binding. These studies suggest that our molecular assay based on surface plasmon
      resonance is not only useful for the analysis of viral-host protein interactions
      but is also applicable for the routine screening of compounds to identify those
      that interfere with the first step of viral entry, thus facilitating the rapid
      development of novel antiviral compounds that target HSV.

PMID- 24079704
TI  - Thermal isomerization of the chromoprotein asFP595 and its kindling mutant A143G:
      QM/MM molecular dynamics simulations.
AB  - Chromoprotein asFP595 and its A143G variant called kindling fluorescent protein
      (KFP) are among the chronologically first species for which trans-cis chromophore
      isomerization has been proposed as a driving force of photoswitching. In spite of
      long-lasting efforts to characterize the route between protein conformations
      referring to the trans and cis forms of the chromophore, the molecular mechanism
      of this transformation is still under debate. We report the results of
      computational studies of the trans-cis isomerization of the anionic and neutral
      chromophore inside the protein matrices in the ground electronic state for both
      variants, asFP595 and KFP. Corresponding free energy profiles (potentials of mean
      force) were evaluated by using molecular dynamics simulations with the quantum
      mechanical-molecular mechanical (QM/MM) forces. The computed free energy barrier
      for the cis-trans ground state (thermal) isomerization reaction is about 2
      kcal/mol higher in KFP than that in asFP595. These results provide interpretation
      of experimental studies on thermal relaxation from the light-induced activation
      of fluorescence of these proteins and correctly show that the A143G mutation in
      asFP595 noticeably increases the lifetime of the fluorescence species.

PMID- 24079705
TI  - Longitudinal trajectories of suicidal ideation and subsequent suicide attempts
      among adolescent inpatients.
AB  - A period of particularly high risk for suicide attempts among adolescent
      inpatients is within 12 months after discharge. However, little is known about
      longitudinal trajectories of suicidal ideation in this high-risk group and how
      these relate to posthospitalization suicide attempts and rehospitalizations. Our
      objectives were to identify these trajectories and examine their relationships
      with posthospitalization psychiatric crises. We also examined predictors of
      trajectory group membership. Participants (N = 376; ages 13-17; 72% female) were
      assessed at hospitalization and 3, 6, and 12 months later. Trajectory groups, and
      their predictors, were identified with latent class growth modeling. We used
      logistic regression to examine associations between trajectory groups and
      likelihood of suicide attempts and rehospitalization, controlling for attempt
      history. Three trajectory groups were identified: (a) subclinical ideators
      (31.6%), (b) elevated ideators with rapidly declining ideation (57.4%), and (c)
      chronically elevated ideators (10.9%). Adolescents in the chronically elevated
      ideation group had 2.29, confidence interval (CI) [1.08, 4.85], p = .03, and
      4.15, CI [1.65, 10.44], p < .01, greater odds of attempting suicide and 3.23, CI
      [1.37, 7.69], p = .01, and 11.20, CI [4.33, 29.01], p < .001, greater odds of
      rehospitalization relative to rapidly declining and subclinical groups,
      respectively. Higher baseline hopelessness was associated with persisting
      suicidal ideation. Results suggest that suicidal ideation severity at
      hospitalization may not be an adequate marker for subsequent suicidal crises. It
      is important to identify adolescents vulnerable to persisting suicidal ideation,
      as they are at highest risk of psychiatric crises. Addressing hopelessness may
      facilitate faster declines in ideation after hospitalization. Results also
      highlight a need for consistent monitoring of these adolescents' suicidal
      ideation after discharge.

PMID- 24079706
TI  - Y Chromosome analysis of prehistoric human populations in the West Liao River
      Valley, Northeast China.
AB  - BACKGROUND: The West Liao River valley in Northeast China is an ecologically
      diverse region, populated in prehistory by human populations with a wide range of
      cultures and modes of subsistence. To help understand the human evolutionary
      history of this region, we performed Y chromosome analyses on ancient human
      remains from archaeological sites ranging in age from 6500 to 2700 BP. RESULTS:
      47 of the 70 individuals provided reproducible results. They were assigned into
      five different Y sub-haplogroups using diagnostic single nucleotide
      polymorphisms, namely N1 (xN1a, N1c), N1c, C/C3e, O3a (O3a3) and O3a3c. We also
      used 17 Y short tandem repeat loci in the non-recombining portion of the Y
      chromosome. There appears to be significant genetic differences between
      populations of the West Liao River valley and adjacent cultural complexes in the
      prehistoric period, and these prehistoric populations were shown to carry similar
      haplotypes as present-day Northeast Asians, but at markedly different
      frequencies. CONCLUSION: Our results suggest that the prehistoric cultural
      transitions were associated with immigration from the Yellow River valley and the
      northern steppe into the West Liao River valley. They reveal the temporal
      continuity of Y chromosome lineages in populations of the West Liao River valley
      over 5000 years, with a concurrent increase in lineage diversity caused by an
      influx of immigrants from other populations.

PMID- 24079707
TI  - A structurally rigid bis(amido) ligand framework in low-coordinate Ni(I), Ni(II),
      and Ni(III) analogues provides access to a Ni(III) methyl complex via oxidative
      addition.
AB  - A structurally persistent bis-amido ligand framework capable of supporting nickel
      compounds in three different oxidation states has been identified. A highly
      unusual, isolable Ni(III) alkyl species has been prepared and characterized via a
      rare example of a two-electron oxidative addition of MeI to Ni(I). 

PMID- 24079708
TI  - Revocation of European patent for neural progenitors highlights patent challenges
      for inventions relating to human embryonic stem cells.
AB  - Cells derived from human embryonic stem cells have great therapeutic potential.
      Patents are key to allowing companies that develop methods of generating such
      cells to recuperate their investment. However, in Europe, inventions relating to
      the use of human embryos for commercial purposes are excluded from patentability
      on moral grounds. The scope of this morality exclusion was recently tested before
      Germany's highest court and before the European Patent Office (EPO), with
      diverging results. The decision by the EPO's Opposition Division to revoke
      EP1040185 relating to neural precursors and methods for their generation has
      received a mixed reception. The decision has very recently been appealed, and the
      outcome of this Appeal should provide more definitive guidance on the scope of
      the morality exclusion. 

PMID- 24079709
TI  - Number of free hydroxyl groups on bile acid phospholipids determines the fluidity
      and hydration of model membranes.
AB  - Interactions of synthetic phospholipids with model membranes determines the drug
      release capabilities of phospholipid vesicles at diseased sites. We performed 1,6
      diphenyl-1,3,5-hexatriene (DPH)-based fluorescence anisotropy, Laurdan-based
      membrane hydration, and differential scanning calorimetry (DSC) studies to
      cognize the interactions of three bile acid phospholipids, lithocholic acid
      phosphocholine (LCA-PC), deoxycholic acid-phosphocholine (DCA-PC), and cholic
      acid-phosphocholine (CA-PC) with model membranes. These studies revealed that
      bile acid phospholipids increases membrane fluidity in DCA-PC > CA-PC > LCA-PC
      order, indicating that induction of membrane fluidity is contingent on the number
      and positioning of free hydroxyl groups on bile acids. Similarly, DCA-PC causes
      maximum membrane perturbations due to the presence of a free hydroxyl group,
      whereas LCA-PC induces gel phase in membranes due to hydrophobic bile acid acyl
      chain interactions. These DCA-PC-induced membrane perturbations induce a drastic
      decrease in phase transition temperature (Tm) as determined by calorimetric
      studies, whereas doping of LCA-PC causes phase transition broadening without
      change in Tm. Doping of CA-PC induces membrane perturbations and membrane
      hydration like DCA-PC but sharpening of phase transition at higher doping
      suggests self-association of CA-PC molecules. Therefore these differential mode
      of interactions between bile acid phospholipids and model membranes would help in
      the future for their use in drug delivery. 

PMID- 24079710
TI  - Comparative adsorption of CO2 by mono-, di-, and triamino-organofunctionalized
      magnesium phyllosilicates.
AB  - Carbon dioxide adsorbents, constituted by organofunctionalized magnesium
      phyllosilicates, were produced using 3-aminopropyltriethoxysilane (AMPTS), N-[3
      (trimethoxysilyl)propyl]-ethylenediamine (TMSPEDA), N-[3-(trimethoxysilyl)propyl]
      diethylenetriamine (TMSPETA), and tetraethoxyorthosilane (TEOS) as silicon
      sources with N/Si ratios of 1, 0.75, 0.5, and 0.25, by conventional and microwave
      heating. Adsorption studies were performed using TGA and temperature programmed
      desorption (TPD) methods. The results showed that the best temperatures for
      adsorption were 41, 45, and 90  degrees C, when magnesium phyllosilicate
      functionalized with TMSPETA, TMSPEDA, and AMPTS, respectively, were used as
      adsorbents. Using TPD technique, the maximum efficiency was found to be between
      0.285 and 0.899 for 100% AMPTS and 33.33% TMSPETA, obtained by conventional
      heating. Adsorption efficiency of the materials prepared by conventional method
      is higher than those obtained using microwave as heating source, except for 100%
      AMPTS. Desorption kinetics of CO2, described using Avrami's model, show that the
      CO2 desorption rate constant is in the range from 0.130 to 0.178 min(-1), similar
      to the values for CO2 desorption from monoetamolamine-functionalized TiO2 and
      Li4SiO4 but in a narrower range of values. 

PMID- 24079711
TI  - Quiescent very small embryonic-like stem cells resist oncotherapy and can restore
      spermatogenesis in germ cell depleted mammalian testis.
AB  - Adult mouse and human testes harbor relatively quiescent, pluripotent very small
      embryonic-like stem cells (VSELs), in addition to actively dividing
      spermatogonial stem cells (SSCs). Here we report that various oncotherapy
      regimens in human cancer patients (n=7) and busulphan treatment (25mg/Kg body
      weight) in eight weeks old male mice (n=15) selectively affects actively dividing
      SSCs, spermatogonia, haploid germ cells and somatic microenvironment resulting in
      germ cell aplasia, whereas VSELs are unaffected and persist in otherwise germ
      cell depleted testis. Testicular VSELs are 2-5 um in size, have high nucleo
      cytoplasmic ratio, SCA-1+/CD45-/LIN- (mice), CD133+/CD45-/LIN- (human survivors
      of childhood cancer) and express various pluripotent transcripts including OCT
      4A. SCA-1 sorted cells from busulphan treated mice testes in vitro formed small
      clusters suggestive of self-renewal and differentiation into progenitors, which
      divide rapidly. Inter-tubular random injections of syngeneic Sertoli cells (105
      cells per testis, n=14) or bone marrow derived mesenchymal cells (104 cells per
      testis, n=16) into the germ cell depleted busulphan treated mice testes, were
      able to restore spermatogenesis from persisting VSELs. Transplanted Sertoli or
      mesenchymal cells possibly were a source of growth factors essential for VSELs
      differentiation. Since sperm formation occurred in situ, various epigenetic
      concerns associated with the 'synthetic gametes' may be eliminated in our
      approach. Ability of mesenchymal cells to restore spermatogenesis may benefit
      existing azoospermic survivors of childhood cancer who were otherwise deprived of
      testicular tissue cryopreservation prior to oncotherapy. Further studies are
      warranted to delineate the underlying mechanisms and to study quality and
      potential of sperm generated by this approach. 

PMID- 24079713
TI  - Is a monovalent vaccine against enterovirus 71 sufficient? A review of
      enterovirus 71 vaccine development based on enterovirus surveillance in Taiwan.

PMID- 24079712
TI  - Genomic pathway analysis reveals that EZH2 and HDAC4 represent mutually exclusive
      epigenetic pathways across human cancers.
AB  - BACKGROUND: Alterations in epigenetic marks, including methylation or
      acetylation, are common in human cancers. For many epigenetic pathways, however,
      direct measures of activity are unknown, making their role in various cancers
      difficult to assess. Gene expression signatures facilitate the examination of
      patterns of epigenetic pathway activation across and within human cancer types
      allowing better understanding of the relationships between these pathways.
      METHODS: We used Bayesian regression to generate gene expression signatures from
      normal epithelial cells before and after epigenetic pathway activation.
      Signatures were applied to datasets from TCGA, GEO, CaArray, ArrayExpress, and
      the cancer cell line encyclopedia. For TCGA data, signature results were
      correlated with copy number variation and DNA methylation changes. GSEA was used
      to identify biologic pathways related to the signatures. RESULTS: We developed
      and validated signatures reflecting downstream effects of enhancer of zeste
      homolog 2(EZH2), histone deacetylase(HDAC) 1, HDAC4, sirtuin 1(SIRT1), and DNA
      methyltransferase 2(DNMT2). By applying these signatures to data from cancer cell
      lines and tumors in large public repositories, we identify those cancers that
      have the highest and lowest activation of each of these pathways. Highest EZH2
      activation is seen in neuroblastoma, hepatocellular carcinoma, small cell lung
      cancer, and melanoma, while highest HDAC activity is seen in pharyngeal cancer,
      kidney cancer, and pancreatic cancer. Across all datasets studied, activation of
      both EZH2 and HDAC4 is significantly underrepresented. Using breast cancer and
      glioblastoma as examples to examine intrinsic subtypes of particular cancers,
      EZH2 activation was highest in luminal breast cancers and proneural
      glioblastomas, while HDAC4 activation was highest in basal breast cancer and
      mesenchymal glioblastoma. EZH2 and HDAC4 activation are associated with
      particular chromosome abnormalities: EZH2 activation with aberrations in genes
      from the TGF and phosphatidylinositol pathways and HDAC4 activation with
      aberrations in inflammatory and chemokine related genes. CONCLUSION: Gene
      expression patterns can reveal the activation level of epigenetic pathways.
      Epigenetic pathways define biologically relevant subsets of human cancers. EZH2
      activation and HDAC4 activation correlate with growth factor signaling and
      inflammation, respectively, and represent two distinct states for cancer cells.
      This understanding may allow us to identify targetable drivers in these cancer
      subsets.

PMID- 24079714
TI  - A feasible strategy of preimplantation genetic diagnosis for carriers with
      chromosomal translocation: Using blastocyst biopsy and array comparative genomic
      hybridization.
AB  - BACKGROUND/PURPOSE: Patients with chromosomal translocation are highly vulnerable
      to produce unbalanced gametes that result in recurrent miscarriages, affected
      offspring, or infertility. Preimplantation genetic diagnosis (PGD) with
      blastomere biopsy and fluorescent in-situ hybridization (FISH) has been used to
      select normal/balanced embryos for transfer. However, FISH is inherent with some
      technical difficulties such as cell fixation and signal reading. Here we
      introduce a strategy of PGD using blastocyst biopsy and array comparative genomic
      hybridization (aCGH) for reproductive problems of patients with chromosomal
      translocation. METHODS: Twelve patients diagnosed as having chromosomal
      translocation who underwent PGD cycles were included in this single-center
      observational study. Blastocyst biopsy was performed and biopsied blastocysts
      were cryopreserved individually. Testing was performed with aCGH, and the euploid
      embryos were transferred in the following thawing cycles. RESULTS: The overall
      diagnostic efficiency was 90.2% (55/61) and the euploidy rate was 32.7% (18/55).
      Ten cycles of thawed embryo transfer (ET) were carried out, resulting in three
      live births and another three ongoing pregnancies with an ongoing pregnancy rate
      of 60%/transfer cycle. The prenatal diagnosis with chorionic villi sampling
      confirmed the results of PGD/aCGH in all six pregnant women. No miscarriage
      happened in our case series. CONCLUSION: Our study demonstrates an effective PGD
      strategy with promising outcomes. Blastocyst biopsy can retrieve more genetic
      material and may provide more reliable results, and aCGH offers not only
      detection of chromosomal translocation but also more comprehensive analysis of 24
      chromosomes than traditional FISH. More cases are needed to verify our results
      and this strategy might be considered in general clinical practice.

PMID- 24079715
TI  - Surgical management and immunohistochemical study of corneal plaques in vernal
      keratoconjunctivitis.
AB  - Two children with shield ulcer in vernal keratoconjunctivitis unresponsive to
      steroid therapy received plaque removal by superficial keratectomy, followed by
      amniotic membrane transplantation (AMT). Hematoxylin and eosin staining of the
      excised corneal specimen revealed a thick layer of eosinophilic material attached
      to the Bowman's layer. These deposits were positive for eosinophil granule major
      basic protein, as confirmed by an immunohistochemical study. The shield ulcer
      healed after the amniotic membrane was removed. No recurrent corneal plaque
      developed, although corneal opacity complicated in both cases. Lamellar
      keratectomy with AMT offers an effective management by removing the cytotoxic
      plaques and protecting the denuded stroma from deposition of inflammatory debris.

PMID- 24079716
TI  - Immunogenicity, reactogenicity, and safety of a human rotavirus vaccine, Rotarix,
      in Taiwanese infants who received a dose of hepatitis B immunoglobulin after
      birth.
AB  - This Phase-IV study evaluated the human rotavirus (RV) vaccine Rotarix (RIX4414)
      to provide additional local clinical data to the Taiwan Food and Drug Association
      (NCT01198769). Healthy infants aged 6-12 weeks who were given a hepatitis B
      immunoglobulin (HBIg) dose after birth, received two doses of RIX4414 (0, 2-month
      schedule). Anti-RV IgA antibody concentrations were measured using ELISA. A total
      of 15 infants were enrolled, and included in the according-to-protocol cohort.
      The anti-RV IgA antibody seroconversion rate 2 months post-Dose 2 was 100% (95%
      confidence interval = 78.2-100) and the geometric mean concentration was 254.7
      U/ml (95% confidence interval = 145.0-447.7). Two episodes of gastroenteritis
      were reported, and one stool sample was tested for RV, which was negative. No
      fatal serious adverse events were reported during the study period between
      November 2010 and April 2011. The two-dose regimen of RIX4414 was highly
      immunogenic and safe when administered to healthy Taiwanese infants who received
      a HBIg dose after birth. TRIAL REGISTRATION NUMBER: NCT01198769.

PMID- 24079717
TI  - Preoperative neutrophil/lymphocyte ratio predicts overall survival but does not
      predict recurrence or cancer-specific survival after curative resection of node
      positive colorectal cancer.
AB  - BACKGROUND: The preoperative ratio of neutrophils to lymphocytes (NLR) has been
      proposed as a marker of poor outcome in patients having a resection for
      colorectal cancer (CRC). This study investigated the association between NLR and
      overall survival, cancer-specific survival and recurrent cancer in patients who
      had a potentially curative resection for node-positive CRC. METHODS: Data on 322
      patients were drawn from a prospectively recorded registry operated on between
      1999 and 2007. Analyses of survival involved the Kaplan-Meier method, Cox
      regression and competing risks Cox regression. RESULTS: Increasing NLR as a
      continuous variable was independently though weakly associated with diminishing
      overall survival after adjustment for other prognostic variables (HR 1.06, 95% CI
      1.01-1.11, p = 0.013). Receiver operating characteristic analysis to dichotomize
      NLR as a predictor of overall survival yielded relatively poor sensitivity (55%),
      specificity (66%) and positive predictive value (56%, CI 47%-64%). Competing
      risks regression also showed that NLR was not independently associated with
      recurrence at any site (HR 1.04, CI 0.97-1.11, p = 0.241) or CRC-specific
      mortality (HR 1.02, CI 0.92-1.12, p = 0.782) but was associated with non-CRC
      mortality (HR 1.09, CI 1.03-1.15, p = 0.004). CONCLUSION: In patients with stage
      C tumor the weak link between NLR and overall mortality was not specific to CRC
      but apparently arose because patients with an elevated inflammatory status
      preoperatively were likely to progress to earlier death but not necessarily
      because of their cancer.

PMID- 24079718
TI  - Combined in vitro-in vivo approach to assess the hepatobiliary disposition of a
      novel oral thrombin inhibitor.
AB  - Two clinical trials and a large set of in vitro transporter experiments were
      performed to investigate if the hepatobiliary disposition of the direct thrombin
      inhibitor prodrug AZD0837 is the mechanism for the drug-drug interaction with
      ketoconazole observed in a previous clinical study. In Study 1, [(3)H]AZD0837 was
      administered to healthy male volunteers (n = 8) to quantify and identify the
      metabolites excreted in bile. Bile was sampled directly from the jejunum by
      duodenal aspiration via an oro-enteric tube. In Study 2, the effect of
      ketoconazole on the plasma and bile pharmacokinetics of AZD0837, the intermediate
      metabolite (AR-H069927), and the active form (AR-H067637) was investigated (n =
      17). Co-administration with ketoconazole elevated the plasma exposure to AZD0837
      and the active form approximately 2-fold compared to placebo, which may be
      explained by inhibited CYP3A4 metabolism and reduced biliary clearance,
      respectively. High concentrations of the active form was measured in bile with a
      bile-to-plasma AUC ratio of approximately 75, indicating involvement of
      transporter-mediated excretion of the compound. AZD0837 and its metabolites were
      further investigated as substrates of hepatic uptake and efflux transporters in
      vitro. Studies in MDCK-MDR1 cell monolayers and P-glycoprotein (P-gp) expressing
      membrane vesicles identified AZD0837, the intermediate, and the active form as
      substrates of P-gp. The active form was also identified as a substrate of the
      multidrug and toxin extrusion 1 (MATE1) transporter and the organic cation
      transporter 1 (OCT1), in HEK cells transfected with the respective transporter.
      Ketoconazole was shown to inhibit all of these three transporters; in particular,
      inhibition of P-gp and MATE1 occurred in a clinically relevant concentration
      range. In conclusion, the hepatobiliary transport pathways of AZD0837 and its
      metabolites were identified in vitro and in vivo. Inhibition of the canalicular
      transporters P-gp and MATE1 may lead to enhanced plasma exposure to the active
      form, which could, at least in part, explain the clinical interaction with
      ketoconazole. 

PMID- 24079720
TI  - 3D Anhydrous proton-transporting nanochannels formed by self-assembly of liquid
      crystals composed of a sulfobetaine and a sulfonic acid.
AB  - Herein we describe anhydrous proton transportation through 3D interconnected
      pathways formed by self-assembled molecular complexes. A thermotropic
      bicontinuous cubic (Cub(bi)) phase has been successfully obtained by mixing a
      wedge-shaped sulfobetaine with benzenesulfonic acid in different ratios. These
      ionic complexes exhibit the Cub(bi) phase in a wide range of temperatures, while
      the single zwitterionic compound shows only a columnar hexagonal phase, and
      benzenesulfonic acid is nonmesomorphic. Anhydrous proton conduction on the order
      of 10(-4) S cm(-1) has been achieved for the mixture in the Cub(bi) phase over
      100  degrees C, which can be useful for the development of new electrolytes for
      the next generation of fuel cells.

PMID- 24079719
TI  - Teleconsultation in children with abdominal pain: a comparison of physician
      triage recommendations and an established paediatric telephone triage protocol.
AB  - BACKGROUND: Quality assessment and continuous quality feedback to the staff is
      crucial for safety and efficiency of teleconsultation and triage. This study
      evaluates whether it is feasible to use an already existing telephone triage
      protocol to assess the appropriateness of point-of-care and time-to-treat
      recommendations after teleconsultations. METHODS: Based on electronic patient
      records, we retrospectively compared the point-of-care and time-to-treat
      recommendations of the paediatric telephone triage protocol with the actual
      recommendations of trained physicians for children with abdominal pain, following
      a teleconsultation. RESULTS: In 59 of 96 cases (61%) these recommendations were
      congruent with the paediatric telephone protocol. Discrepancies were either of
      organizational nature, due to factors such as local referral policies or
      gatekeeping insurance models, or of medical origin, such as milder than usual
      symptoms or clear diagnosis of a minor ailment. CONCLUSIONS: A paediatric
      telephone triage protocol may be applicable in healthcare systems other than the
      one in which it has been developed, if triage rules are adapted to match the
      organisational aspects of the local healthcare system.

PMID- 24079721
TI  - Applications of 5-exo-trig thiyl radical cyclizations for the synthesis of
      thiosugars.
AB  - The application of thiyl-radical-mediated 5-exo-trig cyclization reactions for
      the preparation of a series of C-linked 4-thiofuranoside sugars has been
      investigated. The cyclization reactions were found to proceed in high yield with
      complete regioselectivity and moderate to excellent diastereoselectivity for a
      number of benzyl-protected precursors. The diastereoselectivity of the radical
      cyclization was determined by a number of factors, primarily the stereochemistry
      at the C-2 position and the nature of the substituents attached to the olefin.
      The cyclization reactions proceed via transition-state intermediates that favor
      formation of the 1,2-trans products. For D-sugars, a chairlike transition state
      is proposed. For L-sugars, both chair- and boatlike transition states could be
      considered. Inversion of the stereochemistry at C-4 also induced a significant
      effect on the diastereoselectivity of the radical process. The synthetic route is
      general for both D- and L-sugars and offers a highly novel and efficient strategy
      for accessing C-linked 4-thiofuranosides. A fluorescently labeled thiosugar was
      prepared as a putative glycosidase inhibitor.

PMID- 24079724
TI  - Optimizing endobronchial ultrasound for molecular analysis. How many passes are
      needed?
AB  - BACKGROUND: The current oncologic management of non-small cell lung cancer
      (NSCLC) requires pathologic differentiation between adenocarcinoma and squamous
      cell carcinoma. Furthermore, novel therapies for adenocarcinoma are clinically
      available for specific mutation profiles. Endobronchial ultrasound-guided
      transbronchial needle aspiration (EBUS-TBNA) has been shown to adequately obtain
      specimens for molecular profiling. However, it remains unclear what quantity of
      specimens is needed to provide suitable mutational genotyping for adenocarcinoma.
      The objective of this study was to determine the optimal number of aspirations
      per EBUS-TBNA procedure required in the presence of rapid on-site cytopathology
      evaluation (ROSE) for maximal diagnostic yield for molecular mutational analysis.
      METHODS: From March 2010 to February 2012, cytopathologic data were collected
      from consecutive cases of adenocarcinoma or NSCLC not otherwise specified (NSCLC
      NOS), diagnosed by EBUS-TBNA and ROSE. Samples of material obtained were air
      dried and wet-fixed. Samples were tested for the KRAS, EGFR, and/or ALK
      mutations. MEASUREMENTS AND MAIN RESULTS: Eighty-five patients who underwent EBUS
      TBNA and were diagnosed with adenocarcinoma or NSCLC-NOS were identified. Of the
      85 cases identified, 77 (90.6%) were classified as adenocarcinoma with the
      remaining 8 (9.4%) classified as NSCLC-NOS. Eighty-one of 85 (95.3%) were found
      to be adequate for molecular profiling. The median number of sites sampled was
      one. A median of four passes was needed to obtain adequate molecular profiling of
      95.3%, using EBUS in conjunction with ROSE. CONCLUSIONS: With the use of EBUS
      TBNA and ROSE, a minimum of four needle passes may provide an adequate amount of
      specimen for advanced molecular marker analysis.

PMID- 24079725
TI  - Memory for serial order across domains: An overview of the literature and
      directions for future research.
AB  - From vocabulary learning to imitating sequences of motor actions, the ability to
      plan, represent, and recall a novel sequence of items in the correct order is
      fundamental for many verbal and nonverbal higher level cognitive activities. Here
      we review phenomena of serial order documented across the verbal, visual, and
      spatial short-term memory domains and interpret them with reference to the
      principles of serial order and ancillary assumptions instantiated in contemporary
      computational theories of memory for serial order. We propose that functional
      similarities across domains buttress the notion that verbal, visual, and spatial
      sequences are planned and controlled by a competitive queuing (CQ) mechanism in
      which items are simultaneously active in parallel and the strongest item is
      chosen for output. Within the verbal short-term memory CQ system, evidence
      suggests that serial order is represented via a primacy gradient, position
      marking, response suppression, and cumulative matching. Evidence further
      indicates that output interference operates during recall and that item
      similarity effects manifest during both serial order encoding and retrieval. By
      contrast, the principles underlying the representation of serial order in the
      visual and spatial CQ systems are unclear, largely because the relevant studies
      have yet to be performed. In the spatial domain, there is some evidence for a
      primacy gradient and position marking, whereas in the visual domain there is no
      direct evidence for either of the principles of serial order. We conclude by
      proposing some directions for future research designed to bridge this and other
      theoretical gaps in the literature.

PMID- 24079726
TI  - Masking nanoparticle surfaces for sensitive and selective colorimetric detection
      of proteins.
AB  - We have developed a convenient and efficient colorimetric detection system for
      protein targets using aptamer-gold nanoparticle conjugates. We take advantage of
      the correlation between the catalytic properties and the exposed surface area of
      the nanoparticles, which is inversely proportional to the amount of the aptamer
      bound protein targets. As the concentration of the protein target increases, the
      nanoparticle surface area becomes more masked, thus increasing the reduction time
      of 4-nitrophenol for the color change. We also reduce the detection time by
      either redesigning the aptamer sequences or regulating their density. This
      detection system is highly selective, discriminating the target protein even at a
      concentration 1000 times higher than the limit of detection (LOD). Importantly,
      to the best of our knowledge, the LOD with the unaided eye in this work is the
      lowest for a colorimetric detection system using lysozyme as a model protein (16
      nM). Lysozyme in chicken egg whites is directly analyzed using our detection
      system, whose results are in excellent agreement with the enzyme-linked
      immunosorbent assay (ELISA) analysis. 

PMID- 24079723
TI  - Role of viral and host factors in interferon based therapy of hepatitis C virus
      infection.
AB  - The current standard of care (SOC) for hepatitis C virus (HCV) infection is the
      combination of pegylated interferon (PEG-IFN), Ribavirin and protease inhibitor
      for HCV genotype 1. Nevertheless, this treatment is successful only in 70-80% of
      the patients. In addition, the treatment is not economical and is of immense
      physical burden for the subject. It has been established now, that virus-host
      interactions play a significant role in determining treatment outcomes. Therefore
      identifying biological markers that may predict the treatment response and hence
      treatment outcome would be useful. Both IFN and Ribavirin mainly act by
      modulating the immune system of the patient. Therefore, the treatment response is
      influenced by genetic variations of the human as well as the HCV genome. The goal
      of this review article is to summarize the impact of recent scientific advances
      in this area regarding the understanding of human and HCV genetic variations and
      their effect on treatment outcomes. Google scholar and PubMed have been used for
      literature research. Among the host factors, the most prominent associations are
      polymorphisms within the region of the interleukin 28B (IL28B) gene, but
      variations in other cytokine genes have also been linked with the treatment
      outcome. Among the viral factors, HCV genotypes are noteworthy. Moreover, for
      sustained virological responses (SVR), variations in core, p7, non-structural 2
      (NS2), NS3 and NS5A genes are also important. However, all considered single
      nucleotide polymorphisms (SNPs) of IL28B and viral genotypes are the most
      important predictors for interferon based therapy of HCV infection. 

PMID- 24079727
TI  - Three-dimensional reconstruction identifies misaligned pulmonary veins as
      intrapulmonary shunt vessels in alveolar capillary dysplasia.
AB  - Alveolar capillary dysplasia (ACD) with misalignment of pulmonary veins (MPV) is
      a lethal neonatal lung disease. Death from ACD/MPV is caused by hypoxia, but the
      role of the MPV is unknown. Using 3-dimensional reconstruction of ACD/MPV lung
      tissue, we report that the veins in MPV are intrapulmonary shunt vessels, and
      speculate that MPV contributes to the poor prognosis. 

PMID- 24079728
TI  - Positive selection in the adhesion domain of Mus sperm Adam genes through gene
      duplications and function-driven gene complex formations.
AB  - BACKGROUND: Sperm and testes-expressed Adam genes have been shown to undergo
      bouts of positive selection in mammals. Despite the pervasiveness of positive
      selection signals, it is unclear what has driven such selective bouts. The fact
      that only sperm surface Adam genes show signals of positive selection within
      their adhesion domain has led to speculation that selection might be driven by
      species-specific adaptations to fertilization or sperm competition.
      Alternatively, duplications and neofunctionalization of Adam sperm surface genes,
      particularly as it is now understood in rodents, might have contributed to an
      acceleration of evolutionary rates and possibly adaptive diversification.
      RESULTS: Here we sequenced and conducted tests of selection within the adhesion
      domain of sixteen known sperm-surface Adam genes among five species of the Mus
      genus. We find evidence of positive selection associated with all six Adam genes
      known to interact to form functional complexes on Mus sperm. A subset of these
      complex-forming sperm genes also displayed accelerated branch evolution with
      Adam5 evolving under positive selection. In contrast to our previous findings in
      primates, selective bouts within Mus sperm Adams showed no associations to
      proxies of sperm competition. Expanded phylogenetic analysis including sequence
      data from other placental mammals allowed us to uncover ancient and recent
      episodes of adaptive evolution. CONCLUSIONS: The prevailing signals of rapid
      divergence and positive selection detected within the adhesion domain of
      interacting sperm Adams is driven by duplications and potential
      neofunctionalizations that are in some cases ancient (Adams 2, 3 and 5) or more
      recent (Adams 1b, 4b and 6).

PMID- 24079729
TI  - A simple approach to lifetime learning in genetic programming-based symbolic
      regression.
AB  - Genetic programming (GP) coarsely models natural evolution to evolve computer
      programs. Unlike in nature, where individuals can often improve their fitness
      through lifetime experience, the fitness of GP individuals generally does not
      change during their lifetime, and there is usually no opportunity to pass on
      acquired knowledge. This paper introduces the Chameleon system to address this
      discrepancy and augment GP with lifetime learning by adding a simple local search
      that operates by tuning the internal nodes of individuals. Although not the first
      attempt to combine local search with GP, its simplicity means that it is easy to
      understand and cheap to implement. A simple cache is added which leverages the
      local search to reduce the tuning cost to a small fraction of the expected cost,
      and we provide a theoretical upper limit on the maximum tuning expense given the
      average tree size of the population and show that this limit grows very
      conservatively as the average tree size of the population increases. We show that
      Chameleon uses available genetic material more efficiently by exploring more
      actively than with standard GP, and demonstrate that not only does Chameleon
      outperform standard GP (on both training and test data) over a number of symbolic
      regression type problems, it does so by producing smaller individuals and it
      works harmoniously with two other well-known extensions to GP, namely, linear
      scaling and a diversity-promoting tournament selection method. 

PMID- 24079730
TI  - Commentary on the practical guide for the study of sebaceous glands.
AB  - For many years, the function of the sebaceous gland (SG) was underestimated and
      suggested by Albert M. Kligman as a remnant of human development, a 'living
      fossil with a past but no future'. However, the last two decades of studies and
      the discovery of neuro-endocrine pathways in skin have determined the importance
      of the SG in cutaneous biology and homeostasis. SGs play their role in cutaneous
      homeostasis by contribution to local steroidogenic pathways, antimicrobial
      activity and display of immune (both pro- and anti-inflammatory) properties.
      Despite several important manuscripts and reviews regarding SG biology and
      function, there was an urgent need for a high-quality methodological guide
      through SG identification and quantitative evaluation. In this issue of
      Experimental Dermatology, Hinde et al. present a practical guide to SG research -
      outlining methods, defining immunohistochemical markers and providing guidance to
      both novice and more experienced SG researchers.

PMID- 24079731
TI  - A practical guide for the study of human and murine sebaceous glands in situ.
AB  - The skin of most mammals is characterised by the presence of sebaceous glands
      (SGs), whose predominant constituent cell population is sebocytes, that is, lipid
      producing epithelial cells, which develop from the hair follicle. Besides
      holocrine sebum production (which contributes 90% of skin surface lipids),
      multiple additional SG functions have emerged. These range from antimicrobial
      peptide production and immunomodulation, via lipid and hormone
      synthesis/metabolism, to the provision of an epithelial progenitor cell
      reservoir. Therefore, in addition to its involvement in common skin diseases
      (e.g. acne vulgaris), the unfolding diversity of SG functions, both in skin
      health and disease, has raised interest in this integral component of the
      pilosebaceous unit. This practical guide provides an introduction to SG biology
      and to relevant SG histochemical and immunohistochemical techniques, with
      emphasis placed on in situ evaluation methods that can be easily employed. We
      propose a range of simple, established markers, which are particularly
      instructive when addressing specific SG research questions in the two most
      commonly investigated species in SG research, humans and mice. To facilitate the
      development of reproducible analysis techniques for the in situ evaluation of
      SGs, this methods review concludes by suggesting quantitative (immuno
      )histomorphometric methods for standardised SG evaluation. 

PMID- 24079732
TI  - Dihydrodehydrodiisoeugenol enhances adipocyte differentiation and decreases
      lipolysis in murine and human cells.
AB  - Loss of subcutaneous fat is a hallmark of ageing usually starting in the face.
      Attempts to ameliorate cosmetically the appearance of subcutaneous fat loss have
      been of limited success as they fail to rebuild the missing subcutaneous tissue.
      Ageing-driven loss of subcutaneous fat results from (i) the reduced capacity of
      pre-adipocytes to differentiate into adipocytes and (ii) the fact that adipocytes
      of the elderly secrete increased amounts of TNFalpha, that in turn enhances
      lipolysis, inhibits pre-adipocyte differentiation and induces dedifferentiation
      of adipocytes. The neolignan dihydrodehydrodiisoeugenol (DDE) caused a 30%
      increase in lipid accumulation in murine 3T3-L1 cells. This effect was
      accompanied by an induction of the differentiation-associated transcription
      factors peroxisome proliferator-activated receptorgamma (PPARgamma2),
      CAAT/enhancer-binding protein alpha (C/EBPalpha), fatty acid binding protein 4
      and adiponectin, and a loss of the pre-adipocyte marker Pref1. In addition, DDE
      diminished both basal and TNFalpha-induced lipolysis. Similar results were
      obtained in human subcutaneous (hsc) pre-adipocytes cultured in an age-adapted
      hormone mix with reduced levels of insulin and dexamethasone. In this system, DDE
      significantly increased lipid accumulation by 71% and 94% and was associated with
      an induction of PPARgamma2 and adiponectin mRNA expression. DDE also reduced
      basal lipolysis in mature hsc adipocytes. DDE acted as a partial PPARgamma
      agonist because (i) DDE displaced PPARgamma ligand from the human PPAR ligand
      binding site, (ii) DDE-induced lipid accumulation and (iii) DDE-induced
      adiponectin secretion could be overcome by the addition of PPARgamma antagonists.
      Taken together, these studies identify DDE as a compound well suited to prevent
      and reverse loss of subcutaneous fat. 

PMID- 24079734
TI  - Immunostimulatory activity of murine keratinocyte-derived exosomes.
AB  - It has long been known that keratinocytes influence cutaneous immunity through
      secretion of soluble factors. Exosomes, small membrane vesicles of endocytotic
      origin, have been implicated in intercellular communication processes such as the
      transfer of tumor cell antigens and the activation of recipient dendritic cells
      (DC). However, little is known about immunomodulatory functions of keratinocyte
      derived exosomes. To address this question, we analysed exosome secretion of the
      murine keratinocyte cell line MPEK under steady state as well as inflammatory
      conditions (+/- IFNgamma). These exosomes were readily taken up by bone marrow
      derived DC (BMDC) in vitro resulting in a matured phenotype, as evidenced by
      increased CD40 expression as well as by the production of large amounts of IL-6,
      IL-10 and IL-12. When the transfer of antigen-specific information through
      exosomes was investigated, it was found that keratinocytes took up antigen
      (ovalbumin) and transferred it to their exosomes. However, these antigen
      harbouring exosomes failed to induce antigen-specific T cell responses via BMDC.
      Together, this novel biological function suggests that keratinocytes are able to
      direct unspecific immune processes but do not elicit specific immune responses. 

PMID- 24079735
TI  - Apoptotic signal molecules in skin biopsies of cutaneous lupus erythematosus:
      analysis using tissue microarray.
AB  - Cutaneous lupus erythematosus (CLE) is a heterogeneous autoimmune disease.
      Different pathogenetic mechanisms, including the accumulation of apoptotic
      keratinocytes in CLE, have been reported. Therefore, we investigated whether CLE
      and other inflammatory skin diseases differ with regard to the epidermal
      expression of molecules that are crucial for the initiation and regulation of
      apoptosis. In this study, 241 skin biopsies from patients with CLE, psoriasis
      (PSO), lichen planus (LP) and healthy controls (HCs) were analysed
      immunohistochemically using the tissue microarray (TMA) technique. The TUNEL
      assay and anti-activated caspase-3 antibodies revealed a significant increase of
      apoptotic keratinocytes in CLE lesions compared with HCs. Furthermore, we
      detected a significant increase in the epidermal expression of CD95 in CLE
      specimens compared with PSO, LP and HCs. These data suggest that the accumulation
      of apoptotic keratinocytes in CLE might be due to the increased epidermal
      expression of CD95, resulting in increased activity of the extrinsic apoptotic
      pathway in the disease. 

PMID- 24079733
TI  - Hairless and the polyamine putrescine form a negative regulatory loop in the
      epidermis.
AB  - Hairless (HR) is a nuclear protein with corepressor activity that is highly
      expressed in the skin and hair follicle. Mutations in Hairless lead to hair loss
      accompanied by the appearance of papules (atrichia with papular lesions), and
      similar phenotypes appear when the key polyamine enzymes ornithine decarboxylase
      (ODC) and spermidine/spermine N(1) -acetyltransferase (SSAT) are overexpressed.
      Both ODC and SSAT transgenic mice have elevated epidermal levels of putrescine,
      leading us to investigate the mechanistic link between putrescine and HR. We show
      here that HR and putrescine form a negative regulatory network, as epidermal ODC
      expression is elevated when HR is decreased and vice versa. We also show that the
      regulation of ODC by HR is dependent on the MYC superfamily of proteins, in
      particular MYC, MXI1 and MXD3. Furthermore, we found that elevated levels of
      putrescine lead to decreased HR expression, but that the SSAT-TG phenotype is
      distinct from that found when HR is mutated. Transcriptional microarray analysis
      of putrescine-treated primary human keratinocytes demonstrated differential
      regulation of genes involved in protein-protein interactions, nucleotide binding
      and transcription factor activity, suggesting that the putrescine-HR negative
      regulatory loop may have a large impact on epidermal homeostasis and hair
      follicle cycling. 

PMID- 24079736
TI  - Evidence that Notch and Delta expressions have a role in dermal condensate
      aggregation during wool follicle initiation.
AB  - Notch pathway genes have been implicated in the commitment of mesenchymal cells
      to a wool follicle cell fate. Notch1 and Delta1 transcripts were quantified in
      fetal skin of fine-woolled (Merino) and strong-woolled (Tukidale) sheep at two
      time points: either preceding (d56) or during (d70) the first wave of follicle
      initiation. DIG-labelled probes for both transcripts were localised in the
      epithelium, some mesenchymal cells, and in the dermal condensates of primordia.
      The possibility that condensates selectively incorporated Delta1-labelled
      mesenchymal cells is considered. The involvement of Notch1 in condensate
      formation was also explored in cultured fetal skin explants and whisker papilla
      cells using DAPT to block Notch signalling. In its presence, follicle initiation
      in skin explants was reduced, and the propensity for cultured papilla cells to
      aggregate was abolished. Results suggest that Notch1 activation is a prerequisite
      for mesenchymal aggregation. It is speculated that Delta interactions contribute
      to condensate formation, in vivo. 

PMID- 24079737
TI  - Low environmental humidity induces synthesis and release of cortisol in an
      epidermal organotypic culture system.
AB  - Dry environmental conditions induce a variety of skin pathologies and a recent
      report indicating that cortisol synthesis in epidermis was increased during wound
      healing led us to hypothesize that environmental dryness might induce increased
      cortisol secretion in epidermis. Therefore, we incubated a skin equivalent model
      under dry (relative humidity: less than 10%) and humid (relative humidity:
      approximately 100%) conditions for 48 hours and evaluated cortisol secretion and
      mRNA levels of cortisol-synthesizing enzyme (steroid 11beta-hydroxylase, CYP11B1)
      and IL-1beta. Cortisol secretion was increased threefold, and CYP11B1 and IL
      1beta mRNAs were increased 38-fold and sixfold, respectively, in the dry
      condition versus the humid condition. Occlusion with a water-impermeable plastic
      membrane partially blocked the increases in cortisol secretion and CYP11B1 and IL
      1beta mRNA expression in the dry condition. Thus, environmental dryness might
      induce increased cortisol secretion in epidermis of diseased skin characterized
      by epidermal barrier dysfunction, potentially influencing mental state and
      systemic physiology.

PMID- 24079738
TI  - Human skin melanocyte migration towards stromal cell-derived factor-1alpha
      demonstrated by optical real-time cell mobility assay: modulation of their
      chemotactic ability by alpha-melanocyte-stimulating hormone.
AB  - To identify potential regulators of normal human melanocyte behaviour, we have
      developed an in vitro human melanocyte migration assay, using the optically
      accessible, real-time cell motility assay device TAXIScan. Coating of the glass
      surface with an extracellular matrix that served as scaffolding molecule was
      essential to demonstrate efficient melanocyte migration. Among several chemokines
      tested, stromal cell-derived factor (SDF)-1alpha/CXCL12 was the most effective
      driver of human normal skin melanocytes. Incubation of melanocytes with alpha
      melanocyte-stimulating hormone (MSH) before the assay specifically enhanced CXCR4
      expression and consequently chemotaxis towards SDF-1alpha/CXCL12. These results
      suggest that alpha-MSH acts on melanocytes to produce melanin as well as
      stimulates the cells to migrate to the site where they work through CXCR4 up
      regulation, which is a new dynamic mode of action of alpha-MSH on melanocyte
      physiology. 

PMID- 24079739
TI  - Ligand-independent epidermal growth factor receptor hyperactivation increases
      sebaceous gland size and sebum secretion in mice.
AB  - The epidermal growth factor receptor (EGFR) system is an established regulator of
      the development and homeostasis of the hair follicle and interfollicular
      epidermis. Here, we evaluated EGFR actions on the sebaceous glands (SGs) by
      employing Dsk5 mice, a mutant line in which the EGFR is constitutively activated
      in a ligand-independent manner. Compared to control littermates, Dsk5 mice showed
      increased sebum levels and enlarged SGs, which contained a higher number of cells
      and showed stronger proliferation. c-myc transcript levels were increased in Dsk5
      skin, suggesting that c-myc mediates the proliferative stimuli of the EGFR in the
      SG. Analysis of differentiation markers revealed deregulated expression of Scd1
      and Scd3, indicating that sebaceous lipogenesis is affected in Dsk5 mice. In
      conclusion, our study indicates that the EGFR is an important regulator of
      presebocyte proliferation, contributing to the final cell number, to the size and
      to the lipid output of SGs. 

PMID- 24079740
TI  - A single dose of interleukin-31 (IL-31) causes continuous itch-associated
      scratching behaviour in mice.
AB  - We investigated the effects of a single dose of mouse interleukin-31 (IL-31) on
      scratching behaviour in comparison with spontaneous skin-lesion- or serotonin (5
      HT)- induced scratching behaviour in NC/Nga and BALB/c mice. Intradermal (i.d.)
      injection of IL-31 caused a gradual increase in long-lasting scratching (LLS,
      over 1.5 s) about 3 h after administration followed by a gradual decrease for
      over 24 h after administration. I.d. injection of IL-31 significantly increased
      the total LLS counts/24 h but not short-lasting scratching (SLS, 0.3-1.5 s). In
      skin-lesioned NC/Nga mice, the LLS but not SLS counts were significantly higher
      than those in non-skin-lesioned NC/Nga mice. We also investigated 5-HT-induced
      scratching in BALB/c mice, SLS but not LLS increased immediately after the
      injection and then decreased to baseline after at 20 min. These results suggest
      that IL-31 may participate in the sensation of itching and promote scratching
      behaviour in skin-lesioned NC/Nga mice, an animal model of atopic dermatitis
      (AD). 

PMID- 24079741
TI  - E6 and E7 of human papillomavirus type 18 and UVB irradiation corporately
      regulate interleukin-6 and interleukin-8 expressions in basal cell carcinoma.
AB  - The lack of a human papillomavirus (HPV)-infected skin cancer cell line has
      hampered the investigation of the interaction of UV and HPV in skin
      carcinogenesis. We identified a human basal cell carcinoma (BCC-1/KMC) cell line
      integrated with E6 and E7 genes of high-risk HPV type 18 and demonstrated that
      repression of E6 and E7 results in proliferation inhibition. Sublethal
      ultraviolet-B (UVB) irradiation induced the expressions of interleukin-6 (IL-6)
      and interleukin-8 (IL-8), as well as viral E6 and E7 genes, in BCC-1/KMC cells.
      When E6 and E7 expressions were inhibited, IL-6/IL-8 expressions were repressed.
      Furthermore, IL-6/IL-8 remained inducible by UVB irradiation when E6 and E7 were
      inhibited. These results indicated that IL-6 and IL-8 can be upregulated by viral
      E6 and E7 proteins without UVB irradiation. Moreover, chronic exposure to UVB
      upregulates IL-6 and IL-8 when E6/E7 is induced by UVB. 

PMID- 24079742
TI  - Effects of a topical aqueous oxygen emulsion on collagen deposition and
      angiogenesis in a porcine deep partial-thickness wound model.
AB  - A porcine deep partial-thickness wound model was used to evaluate the effects of
      a newly developed topical aqueous oxygen emulsion (TOE) on wound repair. The
      wounds were treated with TOE, which contains super-saturated oxygen or vehicle
      control. Semiquantitative immunofluorescent staining was performed to examine
      protein production for type I and type III collagen and vascular endothelial
      growth factor (VEGF). Immunofluorescent staining revealed higher protein levels
      of type I and type III collagen and VEGF in the TOE treatment group. Histological
      analysis also revealed improved angiogenesis and granulation tissue formation
      with topical TOE treatment and was consistent with the protein expression. In
      addition, the histology examination demonstrated faster epithelialization in
      wounds treated with TOE. The study suggests that sustained high levels of oxygen
      released by TOE may promote the process of wound repair through increasing
      collagen deposition and angiogenesis as well as stimulating epithelialization. 

PMID- 24079743
TI  - Effects of sphingoid bases on the sphingolipidome in early keratinocyte
      differentiation.
AB  - Keratinocyte sphingolipids are structural elements of epidermal permeability
      barrier and potential regulators of epidermal functions. We tested the influence
      of sphingoid bases sphinganine, sphingosine and phytosphingosine on in vitro
      keratinocyte differentiation. Lipidomic and transcriptomic analysis after
      treatment emphasizes sphinganine and phytosphingosine as potent modulators of
      keratinocyte differentiation and lipid metabolism. Sphinganine treatment
      regulated differentiation and sphingolipid metabolism-related genes, and also
      increased all major ceramide species. Sphingosine treatment increased ceramide
      and phytoceramide pools without changes in dihydroceramides. Phytosphingosine
      treatment markedly increased phytoceramide pools without raising ceramide or
      dihydroceramide levels. Sphinganine treatment increased specifically very long
      chain ceramides essential for intact barrier function. In summary, sphingoid
      bases, especially sphinganine, promote differentiation and ceramide production in
      keratinocytes. Free sphinganine may serve as a dermatological and cosmetic agent
      by enhancing formation and maintenance of an intact epidermal lipid barrier, with
      beneficial effects for skin and hair care applications. 

PMID- 24079746
TI  - Crowdfunding genomics and bioinformatics.

PMID- 24079744
TI  - Deletion of the activating NKG2C receptor and a functional polymorphism in its
      ligand HLA-E in psoriasis susceptibility.
AB  - Psoriasis is an inflammatory, immune-mediated disease of the skin. Several
      studies have suggested that natural killer (NK) cells and their receptors may be
      important for its pathogenesis. Here, we examined whether deletion of the
      activating natural killer receptor gene NKG2C, which has a frequency of 20% in
      the European population, was associated with psoriasis susceptibility. The NKG2C
      deletion and a functional polymorphism in its ligand HLA-E were genotyped in a
      Caucasian cohort of 611 psoriasis cases and 493 controls. We found that the NKG2C
      deletion was significantly increased in cases compared with controls [0.258 vs
      0.200, P = 0.0012, OR = 1.43 (1.15-1.79)]. The low-expressing HLA-E*01:01 allele
      was associated with psoriasis (P = 0.0018), although this association was
      dependent on HLA-C. Our findings support a potential immunoregulatory role for NK
      cells in psoriasis and suggest the importance of future studies to investigate
      the contribution of NK cells and their regulatory receptors to the pathogenesis
      of psoriasis.

PMID- 24079747
TI  - Adapting evidence-based interventions using a common theory, practices, and
      principles.
AB  - Hundreds of validated evidence-based intervention programs (EBIP) aim to improve
      families' well-being; however, most are not broadly adopted. As an alternative
      diffusion strategy, we created wellness centers to reach families' everyday lives
      with a prevention framework. At two wellness centers, one in a middle-class
      neighborhood and one in a low-income neighborhood, popular local activity leaders
      (instructors of martial arts, yoga, sports, music, dancing, Zumba), and motivated
      parents were trained to be Family Mentors. Trainings focused on a framework that
      taught synthesized, foundational prevention science theory, practice elements,
      and principles, applied to specific content areas (parenting, social skills, and
      obesity). Family Mentors were then allowed to adapt scripts and activities based
      on their cultural experiences but were closely monitored and supervised over
      time. The framework was implemented in a range of activities (summer camps,
      coaching) aimed at improving social, emotional, and behavioral outcomes.
      Successes and challenges are discussed for (a) engaging parents and communities;
      (b) identifying and training Family Mentors to promote children and families'
      well-being; and (c) gathering data for supervision, outcome evaluation, and
      continuous quality improvement. To broadly diffuse prevention to families, far
      more experimentation is needed with alternative and engaging implementation
      strategies that are enhanced with knowledge harvested from researchers' past 30
      years of experience creating EBIP. One strategy is to train local parents and
      popular activity leaders in applying robust prevention science theory, common
      practice elements, and principles of EBIP. More systematic evaluation of such
      innovations is needed. 

PMID- 24079749
TI  - Key neuropsychiatric symptoms in common dementias: prevalence and implications
      for caregivers, clinicians, and health systems.
AB  - The purpose of this study was to compare neuropsychiatric symptoms (NPS) among
      people with common dementias and equip interdisciplinary clinicians and health
      services planners with large-sample data necessary to plan care for patients and
      families. We analyzed selected variables from baseline assessments of older
      adults with dementia of one or more etiologies (N = 3,768) from the National
      Alzheimer's Coordinating Center data repository. Dementias included Alzheimer's
      disease (AD), Lewy body dementia (DLB), behavioral variant frontotemporal
      dementia (bvFTD), and vascular dementia (VaD). We compared the prevalence of four
      NPS clusters (agitation/aggression, depression/dysphoria, anxiety,
      irritability/lability) across dementia etiologies and stages using logistic
      regression and AD as the reference group. NPS profiles differed significantly
      across dementia types and stages. Compared with primary AD, DLB was associated
      with greater odds of depression/dysphoria (OR = 1.68, 95% confidence interval
      [CI] 1.28, 2.20) and anxiety (OR = 1.80, 95% CI 1.37, 2.36), with similar
      findings when DLB was diagnosed in combination with AD (depression/dysphoria: OR
      = 1.79, 95% CI 1.11, 2.89; anxiety: OR = 1.88, 95% CI 1.17, 3.02). Primary bvFTD
      was associated with greater odds of agitation/aggression (OR = 1.59, 95% CI 1.17,
      2.18). The prevalence of anxiety and irritability/lability was highest in
      moderate stages of dementia, and agitation/aggression was most prevalent in
      severe dementia. Differential diagnosis and staging of dementias and inclusion of
      single and overlapping etiologies is important for planning and implementing
      appropriate strategies to anticipate, report, and intervene with key NPS that
      complicate home and health care.

PMID- 24079748
TI  - MicroRNA/mRNA profiling and regulatory network of intracranial aneurysm.
AB  - BACKGROUND: Intracranial aneurysm (IA) is one of the most lethal forms of
      cerebrovascular diseases characterized by endothelial dysfunction, vascular
      smooth muscle cell phenotypic modulation, inflammation and consequently loss of
      vessel cells and extracellular matrix degradation. Besides environmental factors,
      genetics seem to be a very important factor in the genesis of this disease.
      Previous mRNA expression studies revealed a large number of differentially
      expressed genes between IA and control tissue. However, microRNAs (miRNA), small
      non-coding RNAs which are post-transcriptional regulators of gene expression,
      have been barely studied. Studying miRNAs could provide a hypothetical mechanism
      underlying rupture of IA. METHODS: A microarray study was carried out to
      determine difference in microRNAs and mRNA between patients' IA tissues and
      controls. Quantitative RT-PCR assay compared the expression level between two
      groups (14 IA domes vs. 14 controls) were used for validation. Validated miRNAs
      were analyzed using Ingenuity Pathway Analysis (IPA) to identify the networks and
      pathways. RESULTS: 18 miRNAs were confirmed by qPCR to be robustly down-regulated
      in 14 ruptured IA patients including hsa-mir-133b, hsa-mir-133a, hsa-mir-1, hsa
      mir-143-3p, hsa-mir-145-3p, hsa-mir-145-5p, hsa-mir-455-5p, hsa-mir-143-5p, hsa
      mir-23b-3p etc., of which 11 miRNAs are clusters: hsa-mir-1/has-mir-133a, hsa-mir
      143/hsa-mir-145, hsa-mir-23b/hsa-mir-24-1, and hsa-mir-29b-2/hsa-mir-29c. 12
      predicted functions were generated using IPA which showed significant
      associations with migration of phagocytes, proliferation of mononuclear
      leukocytes, cell movement of mononuclear leukocytes, cell movement of smooth
      muscle cells etc. CONCLUSION: These data support common disease mechanisms that
      may be under miRNA control and provide exciting directions for further
      investigations aimed at elucidating the miRNA mechanisms and targets that may
      yield new therapies for IA.

PMID- 24079750
TI  - Predictors of diminished levels of social integration in older adults.
AB  - The purpose of this secondary analysis of prospective longitudinal data was to
      determine the variables predictive of diminished social integration in older
      adults over time. Using generalized estimating equations to model diminished
      levels of social integration over the 12-year study period, the following
      variables were predictive of diminished levels of social integration over time:
      bad overall health (odds ratio [OR] = 2.31, 95% confidence interval [CI] 1.39,
      3.83), depressive symptoms (OR = 1.36, 95% CI 1.13, 1.65), positive smoking
      status (OR = 1.40, 95% CI 1.15, 1.71), and decreased religious engagement (OR =
      1.81, 95% CI 1.04, 2.19). A better understanding of predictive factors could
      positively impact resource allocation, prioritization, and case management for
      older adults.

PMID- 24079751
TI  - New corneal findings in chromosome 10 deletion syndrome: report of two cases of
      corneal ectasia of varying severity.
AB  - PURPOSE: To describe corneal changes associated with chromosome 10 terminal
      deletion (chromosome 10, monosomy 10qter) syndrome. METHODS: Report of two cases
      of bilateral corneal ectasia with literature review. RESULTS: Corneal pathology
      has not previously been reported in the limited number of case reports on 10qter
      syndrome. However, Rodrigues et al.(1) have reported sclerocornea in 10q
      translocation. CONCLUSIONS: Ophthalmic manifestations of 10qter syndrome include
      strabismus, lid, and facial anomalies. We present two cases of corneal ectasia of
      varying severity. Possible etiologies include the following: secondary to genetic
      factors, acquired corneal exposure during sleep, or possible intrinsic
      immunocompromise exacerbating ocular surface infections. Corneal ectasia with
      specific histological changes is a feature of various genetic disorders (e.g.,
      Down's, Ehler's Danlos, and Marfan's syndromes). It is unknown whether genetics
      plays a role in the development of corneal changes in 10qter syndrome. Management
      of inflammation and visual rehabilitation in these patients poses a therapeutic
      challenge.

PMID- 24079752
TI  - Cost-effectiveness of adjuvant chemotherapy for curatively resected gastric
      cancer with S-1.
AB  - BACKGROUND: The effectiveness of specific regimens of adjuvant therapy for
      gastric cancer has not been verified by large clinical trials. Recently, several
      large trials attempted to verify the effectiveness of adjuvant therapy. The
      Adjuvant Chemotherapy Trial of TS-1 for Gastric Cancer in Japan, a randomized
      controlled trial of adjuvant S-1 therapy for resected gastric cancer,
      demonstrated significant improvement in overall and relapse-free survival,
      compared to surgery alone. To evaluate value for money of S-1 therapy, cost
      effective analysis was carried out. METHODS: The analysis was carried out from a
      payer's perspective. As an economic measure, cost per quality-adjusted life-year
      (QALY) gained was estimated. Overall survival was estimated by the Kaplan-Meier
      method, up to 5-year observation. Beyond this period, it was simulated by the
      modified Boag model. Utility score is derived from interviews with sampled
      patients using a time trade-off method. Costs were estimated from trial data
      during observation, while in the period beyond observation they were estimated
      using simulation results. To explore uncertainty of the results, qualitative and
      stochastic sensitivity analyses were done. RESULTS: Adjuvant S-1 therapy gained
      1.24 QALYs per patient and increased costs by $3,722 per patient for over
      lifetime (3% discount rate for both effect and costs). The incremental cost
      effectiveness ratio (95% confidence intervals) for over lifetime was estimated to
      be $3,016 ($1,441, $8,840) per QALY. The sensitivity analyses showed the
      robustness of these results. CONCLUSION: Adjuvant S-1 therapy for curatively
      resected gastric cancer is likely cost-effective. This therapy can be accepted
      for wide use in Japan.

PMID- 24079753
TI  - High-precision measurements of (33)S and (34)S fractionation during SO2 oxidation
      reveal causes of seasonality in SO2 and sulfate isotopic composition.
AB  - This study presents high-precision isotope ratio-mass spectrometric measurements
      of isotopic fractionation during oxidation of SO2 by OH radicals in the gas phase
      and H2O2 and transition metal ion catalysis (TMI-catalysis) in the aqueous phase.
      Although temperature dependence of fractionation factors was found to be
      significant for H2O2 and TMI-catalyzed pathways, results from a simple 1D model
      revealed that changing partitioning between oxidation pathways was the dominant
      cause of seasonality in the isotopic composition of sulfate relative to SO2.
      Comparison of modeled seasonality with observations shows the TMI-catalyzed
      oxidation pathway is underestimated by more than an order of magnitude in all
      current atmospheric chemistry models. The three reactions showed an approximately
      mass-dependent relationship between (33)S and (34)S. However, the slope of the
      mass-dependent line was significantly different to 0.515 for the OH and TMI
      catalyzed pathways, reflecting kinetic versus equilibrium control of isotopic
      fractionation. For the TMI-catalyzed pathway, both temperature dependence and
      (33)S/(34)S relationship revealed a shift in the rate-limiting reaction step from
      dissolution at lower temperatures to TMI-sulfite complex formation at higher
      temperatures. 1D model results showed that although individual reactions could
      produce Delta(33)S values between -0.15 and +0.20/00, seasonal changes in
      partitioning between oxidation pathways caused average sulfate Delta(33)S values
      of 00/00 throughout the year. 

PMID- 24079754
TI  - Classification of lectins by pattern recognition using glyconanoparticles.
AB  - Carbohydrate-functionalized gold nanoparticles were employed to differentiate
      plant-legume lectins using a statistical analysis method of linear discriminant
      analysis (LDA). Various carbohydrates were conjugated on gold nanoparticles, and
      the resulting glyconanoparticles were treated with lectins. Changes in the
      localized surface plasmon resonance of the glyconanoparticles upon lectin binding
      were recorded, and the data were subjected to LDA. Results showed that the
      glyconanoparticles successfully differentiated all lectins. 

PMID- 24079755
TI  - Genetic structure of Trypanosoma cruzi in Colombia revealed by a High-throughput
      Nuclear Multilocus Sequence Typing (nMLST) approach.
AB  - BACKGROUND: Chagas disease is a systemic pathology caused by Trypanosoma cruzi.
      This parasite reveals remarkable genetic variability, evinced in six Discrete
      Typing Units (DTUs) named from T. cruzi I to T. cruzi VI (TcI to TcVI). Recently
      newly identified genotypes have emerged such as TcBat in Brazil, Colombia and
      Panama associated to anthropogenic bats. The genotype with the broadest
      geographical distribution is TcI, which has recently been associated to severe
      cardiomyopathies in Argentina and Colombia. Therefore, new studies unraveling the
      genetic structure and natural history of this DTU must be pursued. RESULTS: We
      conducted a spatial and temporal analysis on 50 biological clones of T. cruzi I
      (TcI) isolated from humans with different clinical phenotypes, triatomine bugs
      and mammal reservoirs across three endemic regions for Chagas disease in
      Colombia. These clones were submitted to a nuclear Multilocus Sequence Typing
      (nMLST) analysis in order to elucidate its genetic diversity and clustering.
      After analyzing 13 nuclear housekeeping genes and obtaining a 5821 bp length
      alignment, we detected two robust genotypes within TcI henceforth named TcIDOM
      (associated to human infections) and a second cluster associated to peridomestic
      and sylvatic populations. Additionaly, we detected putative events of
      recombination and an intriguing lack of linkage disequilibrium. CONCLUSIONS:
      These findings reinforce the emergence of an enigmatic domestic T. cruzi genotype
      (TcIDOM), and demonstrates the high frequency of recombination at nuclear level
      across natural populations of T. cruzi. Therefore, the need to pursue studies
      focused on the diferential virulence profiles of TcI strains. The biological and
      epidemiological implications of these findings are herein discussed.

PMID- 24079756
TI  - Health system challenges to integration of mental health delivery in primary care
      in Kenya--perspectives of primary care health workers.
AB  - BACKGROUND: Health system weaknesses in Africa are broadly well known,
      constraining progress on reducing the burden of both communicable and non
      communicable disease (Afr Health Monitor, Special issue, 2011, 14-24), and the
      key challenges in leadership, governance, health workforce, medical products,
      vaccines and technologies, information, finance and service delivery have been
      well described (Int Arch Med, 2008, 1:27). This paper uses focus group
      methodology to explore health worker perspectives on the challenges posed to
      integration of mental health into primary care by generic health system weakness.
      METHODS: Two ninety minute focus groups were conducted in Nyanza province, a poor
      agricultural region of Kenya, with 20 health workers drawn from a randomised
      controlled trial to evaluate the impact of a mental health training programme for
      primary care, 10 from the intervention group clinics where staff had received the
      training programme, and 10 health workers from the control group where staff had
      not received the training). RESULTS: These focus group discussions suggested that
      there are a number of generic health system weaknesses in Kenya which impact on
      the ability of health workers to care for clients with mental health problems and
      to implement new skills acquired during a mental health continuing professional
      development training programmes. These weaknesses include the medicine supply,
      health management information system, district level supervision to primary care
      clinics, the lack of attention to mental health in the national health sector
      targets, and especially its absence in district level targets, which results in
      the exclusion of mental health from such district level supervision as exists,
      and the lack of awareness in the district management team about mental health.
      The lack of mental health coverage included in HIV training courses experienced
      by the health workers was also striking, as was the intensive focus during
      district supervision on HIV to the detriment of other health issues. CONCLUSION:
      Generic health system weaknesses in Kenya impact on efforts for horizontal
      integration of mental health into routine primary care practice, and greatly
      frustrate health worker efforts.Improvement of medicine supplies, information
      systems, explicit inclusion of mental health in district level targets,
      management and supervision to primary care are likely to greatly improve primary
      care health worker effectiveness, and enable training programmes to be followed
      by better use in the field of newly acquired skills. A major lever for horizontal
      integration of mental health into the health system would be the inclusion of
      mental health in the national health sector reform strategy at community, primary
      care and district levels rather than just at the higher provincial and national
      levels, so that supportive supervision from the district level to primary care
      would become routine practice rather than very scarce activity. TRIAL
      REGISTRATION: Trial registration ISRCTN 53515024.

PMID- 24079757
TI  - Role of residents in medical student teaching.

PMID- 24079758
TI  - In reply.

PMID- 24079759
TI  - Enhancer of zeste homolog 2 expression is associated with metastasis and adverse
      clinical outcome in clear cell renal cell carcinoma: a comparative study and
      review of the literature.
AB  - CONTEXT: Enhancer of zeste homolog 2 (EZH2), a histone methyltransferase
      mediating chromatin condensation and epigenetic modulation, is overexpressed in
      various human carcinomas and is associated with adverse clinicopathologic
      characteristics and biologic behavior. The expression of EZH2 in renal cell
      carcinomas (RCCs) has not been fully characterized yet. OBJECTIVE: To evaluate
      the prognostic role of EZH2 in RCC by analyzing the immunohistochemical staining
      pattern of the marker in relation to pathologic features and clinical outcome.
      DESIGN: We correlated the immunolabeling of EZH2 with multiple clinicopathologic
      features, including Fuhrman nuclear grade, pathologic stage, metastatic status,
      and clinical outcome in 223 clear cell RCCs (CRCCs) and 21 papillary RCCs, by
      using tissue microarrays of primary and metastatic cases. RESULTS: Most CRCCs
      (75%) showed positive EZH2 staining, with most primary tumors showing focal
      staining in comparison to nonfocal staining in metastatic cases. In primary
      tumors, EZH2 expression was associated with higher nuclear grade and lower
      pathologic stage. Metastatic tumors showed a higher number of positive cases (81%
      versus 67%) and a more diffuse and more intense pattern of staining than primary
      CRCCs. For the 22 locally advanced primary tumors (T3/4) and 43 metastatic RCCs,
      patients who experienced RCC-related deaths significantly overexpressed the
      marker in comparison to patients who did not experience RCC-related mortality.
      CONCLUSIONS: By showing that EZH2 expression is associated with increased
      metastatic potential and a worse clinical outcome, this study suggests that EZH2
      can serve as a prognostic biomarker for RCC, thus confirming it as a key molecule
      driving oncogenesis and metastasis.

PMID- 24079763
TI  - EDITORIAL: LIFESTYLE AND THERAPEUTICS IN THE ELDERLY.

PMID- 24079760
TI  - Urothelial tumors of the urinary bladder in young patients: a clinicopathologic
      study of 59 cases.
AB  - CONTEXT: Urothelial tumors are rare in young patients. Because of their rarity,
      the natural history of the disease in young patients remains poorly understood.
      OBJECTIVE: To understand the pathologic and clinical features of urothelial
      tumors of the urinary bladder in young patients. DESIGN: We identified 59 young
      patients with urothelial tumors of the urinary bladder treated at our institution
      and analyzed the tumors' pathologic features and the patients' clinical outcomes.
      RESULTS: All patients were 30 years or younger, with a mean age of 23.5 years
      (range, 4-30). Thirty-eight patients (64%) were male, and 21 (36%) were female.
      Most tumors were noninvasive, papillary urothelial tumors (49 of 59; 83%),
      including papillary urothelial neoplasms of low malignant potential (7 of 49;
      14%), low-grade papillary urothelial carcinomas (38 of 49; 78%), and high-grade
      papillary urothelial carcinomas (4 of 49; 8%). Only a few (n=10) of the
      urothelial tumors were invasive, invading the lamina propria (n=5; 50%),
      muscularis propria (n=4; 40%), or perivesical soft tissue (n=1; 10%). Clinical
      follow-up information was available for 41 patients (69%), with a mean follow-up
      time of 77 months. Of 31 patients with noninvasive papillary urothelial tumors,
      only 1 patient (3%) later developed an invasive urothelial carcinoma and died of
      the disease, and 30 of these patients (97%) were alive at the end of follow-up,
      although 10 (32%) had local tumor recurrences. In the 10 patients with invasive
      urothelial carcinomas, 3 patients (30%) died of the disease and 5 others (50%)
      were alive with metastases (the other 2 [20%] were alive with no recurrence).
      CONCLUSION: Urothelial tumors in young patients are mostly noninvasive, papillary
      carcinomas and have an excellent prognosis; however, a small subset of patients
      may present with high-grade invasive urothelial carcinomas that result in poor
      clinical outcomes.

PMID- 24079764
TI  - Protein oxidation and proteolytic signalling in aging.
AB  - A number of studies reported a relation between longevity, oxidative stress and
      age-related diseases. Every aerobic organism is inevitably exposed to a permanent
      flux of free radicals and oxidants. Due to the limited activity of antioxidant
      and repair mechanisms, levels of reactive oxygen species can increase during
      aging. Protein damage caused by elevated levels of free radicals or oxidants has
      an important influence on cellular viability and leads to malfunction of proteins
      in aged cells. In addition, modified and impaired proteins can cross-link and
      form the bases of many senescence-associated alterations and also of
      neurodegenerative diseases. To ensure the maintenance of normal cellular
      functions, eukaryotic cells exert proteolysis through two systems: the
      proteasomal system and the lysosomal system, which is degrading cellular
      components after autophagy. During cellular differentiation and aging, both
      systems are subject to extensive changes that significantly affect their
      proteolytic activity. It has been suggested that highly modified proteins and
      undegradable protein aggregates also affect the intracellular proteolytic
      systems. Therefore, it is essential to understand the relationship between
      protein oxidation, intracellular proteolytic systems and cellular defence
      mechanisms. 

PMID- 24079765
TI  - Molecular gerontology: from homeodynamics to hormesis.
AB  - The science and study of the biological basis of aging, biogerontology, is now a
      well-established field with solid scientific base. A paradigm-shift in
      gerontology has occurred by realising the fact that biological aging occurs in
      spite of the presence of complex homeodynamic pathways of maintenance, repair and
      defence, and there is no "enemy within". This viewpoint separates the modulation
      of aging from the treatment of one or more age-related diseases. A promising
      strategy in biogerontology is to slow down aging and to extend healthspan by
      hormetin-mediated hormesis. Physical, nutritional and mental hormetins, which
      initiate stress responses and strengthen the homeodynamics, are potentially
      effective aging modulators. As a biomedical issue, the biological process of
      aging underlies all major diseases, and while the optimal treatment of every
      disease is a social and moral necessity, preventing the onset of agerelated
      diseases by intervening in the basic process of aging is the best approach for
      designing novel pharmaceutical interventions. 

PMID- 24079766
TI  - Molecular function of tocopherols in age related diseases.
AB  - Tocopherols, with a phytyl side chain in its chroman ring, belong to vitamin E
      family and have several effects on organisms. They are also classified as
      therapeutics against different types of human diseases. Especially important
      roles in cell signaling and gene regulatory mechanisms make tocopherols crucial
      as therapeutic agents. Aging is accompanied with several degenerative disorders
      including cardiovascular, neuronal and metabolic diseases. The role of free
      radical damage in aging has been identified and tocopherols were shown to be
      involved in age related disorders. Recent studies and future directions will be
      focused in this review regarding the molecular functions of tocopherols. 

PMID- 24079767
TI  - Antioxidant clinical trials in mild cognitive impairment and Alzheimer's disease 
      challenges and perspectives.
AB  - Alzheimer's Disease (AD) is a progressive neurodegenerative disorder representing
      the most common form of dementia and the most feared highly disabling age-related
      condition of our time. Hallmarks of AD include a dramatically increasing number
      of cases due to prospected demographics and the absence of a cure. AD is
      incurable as it escapes the formula "one disease, one mechanism, one drug". AD
      has a multifaceted pathophysiology only in part uncovered. Even the proven
      chronological primacy of free radical-related damage in AD-related
      neurodegeneration has not yield successful oxidative stress - lowering trial
      designs. As a consequence, clinical trials of antioxidants in AD have brought
      largely negative conclusions. The aims of this review are to discuss 1. rationale
      for antioxidant trials, 2. reasons for failure of antioxidants in AD therapy, 3.
      potential preventive benefits of natural nutrition against AD onset and 4. the
      enormous relevance of detecting and treating AD risk factors as long as possible
      prior to AD manifestation. 

PMID- 24079768
TI  - Pharmaceutical interventions for frailty and sarcopenia.
AB  - Frailty has emerged as one of the most relevant clinical syndromes in older
      patients. This term relates to the loss of functional reserve that can occur in
      some older people following exposure to one or more low-intensity stressors
      placing them at high risk for developing a number of adverse outcomes such as
      disability, falls, hospitalization and death. Frailty is the outcome of two
      combined effects: the ageing process and other superimposed injuries like chronic
      disease or, indeed, psychological and social stressors. The mechanisms leading to
      frailty typically involve several systems: mainly hormones, oxidative stress,
      inflammation, immunity, and vascular system. One of the most outstanding pillars
      of the frailty syndrome is the loss of muscle quantity and function, referred to
      as sarcopenia. The main bulk of experimental pharmacological interventions
      addressing the clinical problem of frailty have been focused on the use of
      hormones, as replacement therapy in subjects with low or normal circulating basal
      levels of the hormone. Results have been disappointing, except for the case of
      testosterone that have shown some benefits. The effectiveness of other potential
      therapeutic interventions (antioxidants, anti-inflammatory agents, nutritional
      supplements) appears to be limited or has not been explored in detail until now.
      In conclusion, there is an available path to prevent the development of
      disability in older people through the treatment of frailty, its main risk
      factor. Aditional research and further experimental testing will help to identify
      new targets and help to make this journey successful. 

PMID- 24079769
TI  - Pharmacological properties of physical exercise in the elderly.
AB  - Scientific evidence links physical activity to several benefits. Recently, we
      proposed the idea that exercise can be regarded as a drug. As with many drugs,
      dosage is of great importance. However, to issue a public recommendation of
      physical activity in aging is not an easy task. Exercise in the elderly needs to
      be carefully tailored and individualized with the specific objectives of the
      person or group in mind. The beneficial effects of exercise in two of the main
      age-related diseases, sarcopenia and Alzheimer's Disease, are dealt with at the
      beginning of this report. Subsequently, dosage of exercise and the molecular
      signaling pathways involved in its adaptations are discussed. Exercise and aging
      are associated with oxidative stress so the paradox arises, and is discussed, as
      to whether exercise would be advisable for the aged population from an oxidative
      stress point of view. Two of the main redox-sensitive signaling pathways altered
      in old skeletal muscle during exercise, NF-kappaB and PGC-1alpha, are also
      reviewed. The last section of the manuscript is devoted to the age-associated
      diseases in which exercise is contraindicated. Finally, we address the option of
      applying exercise mimetics as an alternative for disabled old people. The overall
      denouement is that exercise is so beneficial that it should be deemed a drug both
      for young and old populations. If old adults adopted a more active lifestyle,
      there would be a significant delay in frailty and dependency with clear benefits
      to individual well-being and to the public's health. 

PMID- 24079770
TI  - Modulation of cell death in age-related diseases.
AB  - Aging is a stage of life of all living organisms. According to the free-radical
      theory, aging cells gradually become unable to maintain cellular homeostasis due
      to the adverse effects of reactive oxygen species (ROS). ROS can cause
      irreversible DNA mutations, protein and lipid damage which are increasingly
      accumulated in the course of time if cells could not overcome these effects by
      the antioxidant defence system. Accrued damaged molecules in cells may either
      induce cellular death or contribute to develop various pathologies. Hence,
      programmed cell death mechanisms, apoptosis and autophagy, play a vital role in
      the aging process. Although they are strictly controlled by various
      interconnected signalling pathways, alterations in their regulations may
      contribute to severe pathologies including cancer, Alzheimer's and Parkinson's
      diseases. In this review, we summarized our current understanding and hypotheses
      regarding oxidative stress and age-related dysregulation of cell death signalling
      pathways. 

PMID- 24079771
TI  - Metalloproteinases and metalloproteinase inhibitors in age-related diseases.
AB  - Degradation of the extracellular matrix is an important feature of embryonic
      development, morphogenesis, angiogenesis, tissue repair and remodeling. It is
      precisely regulated under physiological conditions, but when dysregulated it
      becomes a cause of many diseases, including atherosclerosis, osteoarthritis,
      diabetic vascular complications, and neurodegeneration. Various types of
      proteinases are implicated in extracellular matrix degradation, but the major
      enzymes are considered to be metalloproteinases such as matrix metalloproteinases
      (MMPs) and disintegrin and metalloproteinase domain (ADAMs) that include ADAMs
      with a thrombospondin domain (ADAMTS). This review discusses involvement of the
      major metalloproteinases in some age-related chronic diseases, and examines what
      is currently known about the beneficial effects of their inhibitors, used as new
      therapeutic strategies for treating or preventing the development and progression
      of these diseases. 

PMID- 24079772
TI  - Bioenergetics and mitochondrial dysfunction in aging: recent insights for a
      therapeutical approach.
AB  - The present review points out the role of oxidative stress in aging and the
      potential therapeutic targets of modern antioxidant therapies. Mitochondria are
      essential for several biological processes including energy production by
      generating ATP through the electron transport chain (ETC) located on the inner
      mitochondrial membrane. Due to their relevance in cellular physiology, defects in
      mitochondria are associated with various human diseases. Moreover, several years
      of research have demonstrated that mitochondria have a pivotal role in aging. The
      oxidative stress theory of aging suggests that mitochondria play a key role in
      aging as they are the main cellular source of reactive oxygen species (ROS),
      which indiscriminately damage macromolecules leading to an age-dependent decline
      in biological function. In this review we will discuss the mitochondrial
      dysfunction occurring in aging. In particular, we will focus on the novel
      mitochondria targeted therapies and the new selective molecules and nanocarriers
      technology as potentially effective in targeting mitochondrial dysfunction and
      diseases involving oxidative stress and metabolic failure. 

PMID- 24079773
TI  - Calorie restriction and dietary restriction mimetics: a strategy for improving
      healthy aging and longevity.
AB  - Improvements in health care have increased human life expectancy in recent
      decades, and the elderly population is thus increasing in most developed
      countries. Unfortunately this still means increased years of poor health or
      disability. Since it is not yet possible to modify our genetic background, the
      best anti-aging strategy is currently to intervene on environmental factors,
      aiming to reduce the incidence of risk factors of poor health. Calorie
      restriction (CR) with adequate nutrition is the only non-genetic, and the most
      consistent non-pharmacological intervention that extends lifespan in model
      organisms from yeast to mammals, and protects against the deterioration of
      biological functions, delaying or reducing the risk of many age-related diseases.
      The biological mechanisms of CR's beneficial effects include modifications in
      energy metabolism, oxidative stress, insulin sensitivity, inflammation,
      autophagy, neuroendocrine function and induction of hormesis/xenohormesis
      response. The molecular signalling pathways mediating the anti-aging effect of CR
      include sirtuins, peroxisome proliferator activated receptor G coactivator
      1alpha, AMP-activated protein kinase, insulin/insulin growth factor-1, and target
      of rapamycin, which form a pretty interacting network. However, most people would
      not comply with such a rigorous dietary program; research is thus increasingly
      aimed at determining the feasibility and efficacy of natural and/or
      pharmacological CR mimetic molecules/ treatments without lowering food intake,
      particularly in mid- to late-life periods. Likely candidates act on the same
      signalling pathways as CR, and include resveratrol and other polyphenols,
      rapamycin, 2-deoxy-D-glucose and other glycolytic inhibitors, insulin pathway and
      AMP-activated protein kinase activators, autophagy stimulators, alpha-lipoic
      acid, and other antioxidants. 

PMID- 24079774
TI  - Anticarcinogenic, cardioprotective, and other health benefits of tomato compounds
      lycopene, alpha-tomatine, and tomatidine in pure form and in fresh and processed
      tomatoes.
AB  - Tomatoes produce the bioactive compounds lycopene and alpha-tomatine that are
      reported to have potential health-promoting effects in animals and humans, but
      our understanding of the roles of these compounds in the diet is incomplete. Our
      current knowledge gained from the chemistry and analysis of these compounds in
      fresh and processed tomatoes and from studies on their bioavailability,
      bioactivity, and mechanisms of action against cancer cells and other beneficial
      bioactivities including antibiotic, anti-inflammatory, antioxidative,
      cardiovascular, and immunostimulating effects in cells, animals, and humans is
      discussed and interpreted here. Areas for future research are also suggested. The
      collated information and suggested research might contribute to a better
      understanding of the agronomical, biochemical, chemical, physiological,
      molecular, and cellular bases of the health-promoting effects and facilitate and
      guide further studies needed to optimize the use of lycopene and alpha-tomatine
      in pure form and in fresh tomatoes and processed tomato products to help prevent
      or treat human disease. 

PMID- 24079775
TI  - Chikungunya virus: emerging targets and new opportunities for medicinal
      chemistry.
AB  - Chikungunya virus is an emerging arbovirus that is widespread in tropical regions
      and is spreading quickly to temperate climates with recent epidemics in Africa
      and Asia and documented outbreaks in Europe and the Americas. It is having an
      increasingly major impact on humankind, with potentially life-threatening and
      debilitating arthritis. There is no treatment available, and only in the past 24
      months have lead compounds for development as potential therapeutics been
      reported. This Perspective discusses the chikungunya virus as a significant, new
      emerging topic for medicinal chemistry, highlighting the key viral target
      proteins and their molecular functions that can be used in drug design, as well
      as the most important ongoing developments for anti-chikungunya virus research.
      It represents a complete picture of the current medicinal chemistry of
      chikungunya, supporting the development of chemotherapeutics through drug
      discovery and design targeting this virus. 

PMID- 24079776
TI  - Efficacy and safety of NMDA receptor antagonists augmentation therapy for
      schizophrenia: an updated meta-analysis of randomized placebo-controlled trials.

PMID- 24079778
TI  - Evaluation of visual and taste preferences of some gluten-free commercial
      products in a group of celiac children.
AB  - The purpose of this study was to investigate the visual and taste liking of three
      commercial gluten-free (GF) foods in a group of celiac children. Thirty celiac
      children, with diagnosis of celiac disease from more than 2 years, were recruited
      and 28 (21 females and 7 males, mean age 8.7 years) completed the study. Subjects
      performed individually six sensory tests, two for each product in different days
      separated by a week. In the test day, children had to evaluate the liking of the
      same type of product but of different four brands, before and after tasting them
      with a 5-point facial rating scale. Overall, the results showed that the majority
      of children appreciated more the appearance than the taste of all the GF products
      analysed. The present study provides the first and useful indications on the
      hedonic perceptions of celiac children about some commercial GF products.

PMID- 24079779
TI  - The pivotal role of oxyallyl diradicals in photo-Favorskii rearrangements:
      transient spectroscopic and computational studies.
AB  - The photochemistry of the hydroxybenzocycloalkanonyl derivatives 6b-e provides
      the triplet oxyallyl diradicals (3)9 that decay via intersystem crossing to their
      more stable singlet isomers (1)9. Vibrationally resolved transient spectra of
      (3)9 were recorded by pump-probe spectroscopy and laser flash photolysis. It was
      found that the ring strain dependent rate of intersystem crossing is the rate
      limiting step in the formation of photo-Favorskii or solvolysis reaction products
      in water. The reactivities of open-shell singlet oxyallyls (1)9a-e determine the
      product ratios due to their relative abilities to form the corresponding
      cyclopropanones 10. The smallest five-membered derivative, (1)9b, represents the
      first example of an oxyallyl diradicaloid that cannot form cyclopropanone 10b or
      the isomeric allene oxide 13b; instead, it is eventually trapped by water to form
      the sole solvolysis product 12b. Our observations provide a comprehensive
      overview of the role of oxyallyl diradicals in reaction mechanisms and offer a
      new strategy to stabilize open-shell singlet diradicals. 

PMID- 24079780
TI  - Positional plagiocephaly: an analysis of the literature on the effectiveness of
      current guidelines.
AB  - OBJECT: Positional plagiocephaly (PP) has been on the rise in recent years. In
      this review, the authors' aim was to assess the effectiveness of current
      recommendations to parents on this exceedingly common problem through a
      comprehensive literature search. Additionally, the current treatment options and
      the most recent studies on PP are reviewed. METHODS: A search of the existing
      literature was conducted to obtain all relevant studies on guidelines,
      recommendations, parental and clinician practices, and epidemiological aspects.
      RESULTS: Although the incidence and risk factors for PP have been well
      delineated, there continues to be debates on its management and association with
      developmental delays. Current guidelines and recommendations on prevention set by
      the American Association of Pediatrics may not be easily followed by both parents
      and clinicians. There is also evidence that certain populations, including those
      with lower education, socioeconomic status, and in particular geographic regions
      may be more affected by the condition. Additionally, the marketing and financial
      aspects of PP treatments exist and should be addressed. CONCLUSIONS: Better
      awareness and education are necessary to inform the population as a whole,
      although certain populations should be given special attention. Additionally,
      current guidelines and recommendations can be modified to foster a better grasp
      of the condition by both parents and clinicians. Adjusting current
      recommendations, introducing initiatives, and offering elaborate educational
      campaigns would help deliver these aims. Educating parents on PP as early as
      possible through clearer guidelines and close monitoring is central to preventing
      and managing this common condition.

PMID- 24079781
TI  - Orthotic (helmet) therapy in the treatment of plagiocephaly.
AB  - OBJECT: The goal of this study was to review the current literature on orthotic
      (helmet) therapy use in the treatment of deformational plagiocephaly. METHODS:
      PubMed was used to search English articles using the medical subject headings
      "deformational plagiocephaly" and "orthosis," and "deformational plagiocephaly"
      and "helmet." RESULTS: Forty-two articles were found. There were no Class I
      studies, 7 Class II studies, 1 Class III study, and 13 Class IV studies. Cranial
      orthoses have been shown to be effective in treating deformational plagiocephaly.
      It continues to be debated as to whether the statistical significance of
      treatment with cranial orthoses compared with conservative therapies is
      clinically significant. Children older than 12 months of age with deformational
      plagiocephaly may still benefit from orthotic therapy. The long-term effects of
      orthotic therapy are controversial. CONCLUSIONS: There is a lack of Class I
      literature evidence supporting the use of helmet therapy in deformational
      plagiocephaly. There are controversies surrounding the use of orthotic therapy
      such as appropriate use, cost, use in older children, and long-term outcomes.
      Clinical indications for orthotic therapy need to be better defined with further
      research studies.

PMID- 24079782
TI  - Complications associated with molding helmet therapy for positional
      plagiocephaly: a review.
AB  - Molding helmet therapy is a widely accepted treatment for positional
      plagiocephaly that is generally considered to be low risk. Multiple large outcome
      studies have shown good results, but adverse events are rarely reported. The
      literature on helmet therapy was reviewed to clarify the clinical experience with
      associated complications. Although significant complications were extremely rare,
      there was a large degree of variability in detection of lesser problems such as
      minor skin irritation. Patients with a primarily brachycephalic morphology may be
      at higher risk for poorly fitting orthoses. Most reported complications are minor
      and self-limited. Maintenance of good helmet hygiene appears to be the most
      effective strategy for reducing or eliminating complications. 

PMID- 24079783
TI  - Efficacy of passive helmet therapy for deformational plagiocephaly: report of
      1050 cases.
AB  - OBJECT: There has been a tremendous increase in the incidence of deformational
      plagiocephaly in children throughout the world. Therapeutic options include
      observation, active counterpositioning, external orthotics, and surgery. The
      current treatment in the US is highly debated, but it typically includes external
      orthotic helmets in patients with moderate to severe plagiocephaly presenting
      between 4 and 10 months of age or in children with significant comorbidities
      limiting passive (no-pressure) therapy. The present study was designed to
      evaluate 3 key issues: 1) the accuracy of the Argenta classification in defining
      a progressive degree of severity, 2) identification of an upper age limit when
      treatment is no longer effective, and 3) the effectiveness of an off-the-shelf
      prefabricated helmet in correcting deformational plagiocephaly. METHODS: An
      institutional review board-approved retrospective study was conducted of all
      patients at the authors' clinic in whom deformational plagiocephaly was assessed
      using the Argenta classification system over a 6-year period; the patients
      underwent helmet therapy, and a minimum of 3 clinic visits were recorded.
      Inclusion criteria consisted of an Argenta Type II-V plagiocephalic deformity.
      Patients' conditions were categorized both by severity of the deformity and by
      patients' age at presentation. Statistical analysis was conducted using survival
      analysis. RESULTS: There were 1050 patients included in the study. Patients with
      Type III, IV, and V plagiocephaly required progressively longer for deformity
      correction to be achieved than patients with Type II plagiocephaly (53%, 75%, and
      81% longer, respectively [p < 0.0001]). This finding verified that the Argenta
      stratification indicated a progressive severity of deformity. No statistically
      significant difference in the time to correction was noted among the different
      age categories, which suggests that the previously held upper time limit for
      correction may be inaccurate. An overall correction rate to Type I plagiocephaly
      of 81.6% was achieved irrespective of severity and degree of the original
      deformity. This suggests that an inexpensive off-the-shelf molding helmet is
      highly effective and that expensive custom-fitted orthoses may not be necessary.
      The patients in the older age group (> 12 months) did not have a statistically
      significant longer interval to correction than the patients in the youngest age
      group (< 3 months). The mean length of follow-up was 6.3 months. CONCLUSIONS:
      Patients treated with passive helmet therapy in the older age group (> 12 months)
      had an improvement in skull shape within the same treatment interval as the
      patients in the younger age group (< 3 months). This study supports the use of
      passive helmet therapy for improvement in deformational plagiocephaly in infants
      from birth to 18 months of age and verifies the stratification of degree of
      deformity used in the Argenta classification system.

PMID- 24079784
TI  - Comparative effectiveness of treatments for cerebral arteriovenous malformations.

PMID- 24079785
TI  - 5-Aminolevulinic acid-guided resection of bone-invasive meningiomas.

PMID- 24079786
TI  - Management of plagiocephaly.

PMID- 24079787
TI  - Role of endoscopic ultrasonography in the diagnosis of acute and chronic
      pancreatitis.
AB  - Endoscopic ultrasonography (EUS) can be a useful tool for detecting underlying
      causes of acute pancreatitis and establishing the severity of fibrosis in chronic
      pancreatitis. Ancillary techniques include fine needle aspiration and core
      biopsy, bile collection for crystal analysis, pancreatic function testing, and
      celiac plexus block. This review focuses on the role of EUS in the diagnosis of
      acute and chronic pancreatitis. 

PMID- 24079788
TI  - Endoscopic management of acute biliary pancreatitis.
AB  - Acute pancreatitis represents numerous unique challenges to the practicing
      digestive disease specialist. Clinical presentations of acute pancreatitis vary
      from trivial pain to severe acute illness with a significant risk of death.
      Urgent endoscopic treatment of acute pancreatitis is considered when there is
      causal evidence of biliary pancreatitis. This article focuses on the diagnosis
      and endoscopic treatment of acute biliary pancreatitis. 

PMID- 24079789
TI  - Preventing pancreatitis after endoscopic retrograde cholangiopancreatography.
AB  - Post-endoscopic retrograde cholangiopancreatography (ERCP) pancreatitis is a
      common and potentially devastating complication of ERCP. Advances in risk
      stratification, patient selection, procedure technique, and prophylactic
      interventions have substantially improved the endoscopists' ability to prevent
      this complication. This article presents the evidence-based approaches to
      preventing post-ERCP pancreatitis and suggests timely research questions in this
      important area. 

PMID- 24079790
TI  - Endoscopic therapy of necrotizing pancreatitis and pseudocysts.
AB  - Endoscopic therapy has become an essential component in the management of
      postpancreatitis complications, such as infected and/or symptomatic pancreatic
      pseudocysts and walled-off necrosis. However, although there have been 2 recent
      randomized, controlled trials performed, a general lack of comparative
      effectiveness data regarding the timing, indications, and outcomes of these
      procedures has been a barrier to the development of practice standards for
      therapeutic endoscopists managing these issues. This article reviews the
      available data and expert consensus regarding indications for endoscopic
      intervention, timing of procedures, endoscopic technique, periprocedural
      considerations, and complications. 

PMID- 24079791
TI  - Endoscopic therapy for acute recurrent pancreatitis.
AB  - Endoscopy plays an important role in both the diagnosis and the initial
      management of recurrent acute pancreatitis, as well as the investigation of
      refractory disease, but it has known limitations and risks. Sound selective use
      of these therapies, complemented with other lines of investigation such as
      genetic testing, can dramatically improve frequency of attacks and associated
      quality of life. Whether endoscopic therapy can reduce progression to chronic
      pancreatitis, or reduce the risk of malignancy, is debatable, and remains to be
      proven. 

PMID- 24079792
TI  - Endoscopic therapy for chronic pancreatitis.
AB  - Endoscopic therapy is recommended as the first-line therapy for painful chronic
      pancreatitis with an obstacle on the main pancreatic duct (MPD). The clinical
      response should be evaluated at 6 to 8 weeks. Calcified stones that obstruct the
      MPD are first treated by extracorporeal shockwave lithotripsy; dominant MPD
      strictures are optimally treated with a single, large, plastic stent that should
      be exchanged within 1 year even in asymptomatic patients. Pancreatic pseudocysts
      for which therapy is indicated and are within endoscopic reach should be treated
      by endoscopy. 

PMID- 24079793
TI  - ERCP for biliary strictures associated with chronic pancreatitis.
AB  - Chronic pancreatitis (CP)-related common bile duct (CBD) strictures are more
      difficult to treat endoscopically compared with benign biliary strictures because
      of their nature, particularly in patients with calcific CP. Before any attempt at
      treatment, malignancy must be excluded. Single plastic stents can be used for
      immediate symptom relief and as "bridge to surgery and/or bridge to decision,"
      but are not suitable for definitive treatment of CP-related CBD strictures
      because of long-term poor results. Temporary simultaneous placement of multiple
      plastic stents has a high technical success rate and provides good long-term
      results. 

PMID- 24079794
TI  - Endoscopic ultrasonography-guided drainage of the pancreatic duct.
AB  - Over the last 2 decades there has been continuing development in endoscopic
      ultrasonography (EUS). EUS-guided pancreatic drainage is an evolving procedure
      that can be offered to patients who are high-risk surgical candidates and in whom
      the pancreatic duct cannot be accessed by endoscopic retrograde pancreatography.
      Although EUS-guided pancreatic drainage is a minimally invasive alternative
      option to surgery and interventional radiology, owing to its complexity and
      potential for fulminant complications it is recommended that these procedures be
      performed by highly skilled endoscopists. Additional data are needed to define
      risks and long-term outcomes more accurately via a dedicated prospective
      registry. 

PMID- 24079795
TI  - Endoscopic therapy for pancreatic duct leaks and disruptions.
AB  - Pancreatitis, whether acute or chronic, can lead to a plethora of complications,
      such as fluid collections, pseudocysts, fistulas, and necrosis, all of which are
      secondary to leakage of secretions from the pancreatic ductal system. Partial and
      side branch duct disruptions can be managed successfully by transpapillary
      pancreatic duct stent placement, whereas patients with disconnected pancreatic
      duct syndrome require more complex endoscopic interventions or multidisciplinary
      care for optimal treatment outcomes. This review discusses the current status of
      endoscopic management of pancreatic duct leaks and emerging concepts for the
      treatment of disconnected pancreatic duct syndrome. 

PMID- 24079796
TI  - Autoimmune pancreatitis: role of endoscopy in diagnosis and treatment.
AB  - This review addresses the role of endoscopy in the diagnosis and treatment of
      autoimmune pancreatitis (AIP) and provides a diagnostic process for patients with
      suspected AIP. When should AIP be suspected? When can it be diagnosed without
      endoscopic examination? Which endoscopic approaches are appropriate in suspected
      AIP, and when? What are the roles of diagnostic endoscopic retrograde
      pancreatography, endoscopic biopsies, and IgG4 immunostaining? What is the proper
      use of the steroid trial in the diagnosis of AIP in patients with indeterminate
      computed tomography imaging? Should biliary stenting be performed in patients
      with AIP with obstructive jaundice? 

PMID- 24079797
TI  - Palliation of pancreatic ductal obstruction in pancreatic cancer.
AB  - Pancreatic stenting for patients with obstructive pain secondary to a malignant
      pancreatic duct stricture is safe and effective, and should be considered a
      therapeutic option. Although pancreatic stenting does not seem to be effective
      for patients with chronic pain, it may be beneficial in those with obstructive
      type pains, pancreatic duct disruption, or smoldering pancreatitis. Fully covered
      metal stents may be an option, but data on their use are limited. Further
      studies, including prospective randomized studies comparing plastic and metal
      stents in these indications, are needed to further validate and confirm these
      results. 

PMID- 24079798
TI  - Advances in pancreatic endoscopy.

PMID- 24079799
TI  - Effective endoscopic management of pancreatic diseases.

PMID- 24079800
TI  - Analyses of genetic diversity in five Canadian dairy breeds using pedigree data.
AB  - The issue of loss of animal genetic diversity, worldwide in general and in Canada
      in particular, has become noteworthy. The objective of this study was to analyze
      the trend in within-breed genetic diversity and identify the major causes of loss
      of genetic diversity in five Canadian dairy breeds. Pedigrees were analyzed using
      the software EVA (evolutionary algorithm) and CFC (contribution, inbreeding,
      coancestry), and a FORTRAN package for pedigree analysis suited for large
      populations (PEDIG). The average rate of inbreeding in the last generation
      analyzed (2003 to 2007) was 0.93, 1.07, 1.26, 1.09 and 0.80% for Ayrshire, Brown
      Swiss, Canadienne, Guernsey and Milking Shorthorn, respectively, and the
      corresponding estimated effective population sizes were 54, 47, 40, 46 and 66,
      respectively. Based on coancestry coefficients, the estimated effective
      population sizes in the last generation were 62, 76, 43, 61 and 76, respectively.
      The estimated percentage of genetic diversity lost within each breed over the
      last four decades was 6, 7, 11, 8 and 5%, respectively. The relative proportion
      of genetic diversity lost due to random genetic drift in the five breeds ranged
      between 59.3% and 89.7%. The results indicate that each breed has lost genetic
      diversity over time and that the loss is gaining momentum due to increasing rates
      of inbreeding and reduced effective population sizes. Therefore, strategies to
      decrease rate of inbreeding and increase the effective population size are
      advised. 

PMID- 24079801
TI  - Bolbase: a comprehensive genomics database for Brassica oleracea.
AB  - BACKGROUND: Brassica oleracea is a morphologically diverse species in the family
      Brassicaceae and contains a group of nutrition-rich vegetable crops, including
      common heading cabbage, cauliflower, broccoli, kohlrabi, kale, Brussels sprouts.
      This diversity along with its phylogenetic membership in a group of three diploid
      and three tetraploid species, and the recent availability of genome sequences
      within Brassica provide an unprecedented opportunity to study intra- and inter
      species divergence and evolution in this species and its close relatives.
      DESCRIPTION: We have developed a comprehensive database, Bolbase, which provides
      access to the B. oleracea genome data and comparative genomics information. The
      whole genome of B. oleracea is available, including nine fully assembled
      chromosomes and 1,848 scaffolds, with 45,758 predicted genes, 13,382 transposable
      elements, and 3,581 non-coding RNAs. Comparative genomics information is
      available, including syntenic regions among B. oleracea, Brassica rapa and
      Arabidopsis thaliana, synonymous (Ks) and non-synonymous (Ka) substitution rates
      between orthologous gene pairs, gene families or clusters, and differences in
      quantity, category, and distribution of transposable elements on chromosomes.
      Bolbase provides useful search and data mining tools, including a keyword search,
      a local BLAST server, and a customized GBrowse tool, which can be used to extract
      annotations of genome components, identify similar sequences and visualize
      syntenic regions among species. Users can download all genomic data and explore
      comparative genomics in a highly visual setting. CONCLUSIONS: Bolbase is the
      first resource platform for the B. oleracea genome and for genomic comparisons
      with its relatives, and thus it will help the research community to better study
      the function and evolution of Brassica genomes as well as enhance molecular
      breeding research. This database will be updated regularly with new features,
      improvements to genome annotation, and new genomic sequences as they become
      available. Bolbase is freely available at http://ocri-genomics.org/bolbase.

PMID- 24079802
TI  - Toward knowledge support for analysis and  interpretation of complex traits.
AB  - The systematic description of complex traits, from the organism to the cellular
      level, is important for hypothesis generation about underlying disease
      mechanisms. We discuss how intelligent algorithms might provide support, leading
      to faster throughput.

PMID- 24079803
TI  - Multiwalled carbon nanotubes and c60 fullerenes differentially impact the
      accumulation of weathered pesticides in four agricultural plants.
AB  - The effect of multiwalled carbon nanotubes (MWCNT) or C60 fullerenes on the
      uptake of weathered chlordane or DDx (DDT + metabolites) by Cucurbita pepo
      (zucchini), Zea mays (corn), Solanum lycopersicum (tomato), and Glycine max
      (soybean) was investigated. The plants were grown in 50 g of soil with weathered
      chlordane (2150 ng/g) and DDx (118 ng/g) that was amended with 0, 500, 1000, or
      5000 mg/kg MWCNT or C60. After 28 d, the root and shoot content of chlordane
      components and DDx was determined by GC-MS. Zucchini and tomato growth were
      unaffected by carbon nanomaterial coexposure, although C60 at 500 mg/kg reduced
      corn and soybean biomass by 36.5-45.0%. Total chlordane content ranged from 1490
      (tomato) to 4780 (zucchini) ng; DDx amounts ranged from 77.8 (corn) to 395 ng
      (zucchini). MWCNT coexposure decreased chlordane and DDx accumulation 21-80%
      across all crops, depending on species and nanotube concentration. Conversely,
      C60 had species- and contaminant-specific effects on pesticide uptake, ranging
      from complete suppression of DDx uptake (corn/tomato) to 34.9% increases in
      chlordane accumulation (tomato/soybean). The data show that pesticide
      accumulation varies greatly with crop species and carbon nanomaterial
      type/concentration. These findings have implications for food safety and for the
      use of engineered nanomaterials in agriculture. 

PMID- 24079804
TI  - The bilaterian roots of cordon-bleu.
AB  - BACKGROUND: The actin cytoskeleton is essential for many physiological processes
      of eukaryotic cells. The emergence of new actin fibers is initiated by actin
      nucleators. Whereas most of them are evolutionary old, the cordon-bleu actin
      nucleator is classified as vertebrate specific. FINDINGS: Using sensitive methods
      for sequence similarity detection, we identified homologs of cordon-bleu not only
      in non-vertebrate chordates but also in arthropods, molluscs, annelids and
      platyhelminthes. These genes contain only a single WH2 domain and therefore
      resemble more the vertebrate cordon-bleu related 1 protein than the three WH2
      domain containing cordon-bleu. Furthermore, we identified a homolog of the N
      terminal, ubiquitin like, cobl domain of cordon-bleu in the cnidarian
      Nematostella vectensis. CONCLUSION: Our results suggest that the ur-form of the
      cordon-bleu protein family evolved already with the emergence of the bilateria by
      the combination of existing cobl and WH2 domains. Following a vertebrate specific
      gene-duplication, one copy gained two additional WH2 domains leading to the actin
      nucleating cordon-bleu. The function of the ur-form of the cordon-bleu protein
      family is so far unknown. The identification of a homolog in the model organism
      Drosophila melanogaster could facilitate its experimental characterization.

PMID- 24079806
TI  - Estimated risk of HIV acquisition and practice for preventing occupational
      exposure: a study of healthcare workers at Tumbi and Dodoma Hospitals, Tanzania.
AB  - BACKGROUND: Healthcare workers (HCWs) are at risk of acquiring human immuno
      deficiency virus (HIV) and other infections via exposure to infectious patients'
      blood and body fluids. The main objective of this study was to estimate the risk
      of HIV transmission and examine the practices for preventing occupational
      exposures among HCWs at Tumbi and Dodoma Hospitals in Tanzania. METHODS: This
      study was carried out in two hospitals, namely, Tumbi in Coast Region and Dodoma
      in Dodoma Region. In each facility, hospital records of occupational exposure to
      HIV infection and its management were reviewed. In addition, practices to prevent
      occupational exposure to HIV infection among HCWs were observed. RESULTS: The
      estimated risk of HIV transmission due to needle stick injuries was calculated to
      be 7 cases per 1,000,000 HCWs-years. Over half of the observed hospital
      departments did not have guidelines for prevention and management of occupational
      exposure to HIV infections and lacked well displayed health and safety
      instructions. Approximately, one-fifth of the hospital departments visited failed
      to adhere to the instructions pertaining to correlation between waste materials
      and the corresponding colour coded bag/container/safety box. Seventy four percent
      of the hospital departments observed did not display instructions for handling
      infectious materials. Inappropriate use of gloves, lack of health and safety
      instructions, and lack of use of eye protective glasses were more frequently
      observed at Dodoma Hospital than at Tumbi Hospital. CONCLUSIONS: The poor quality
      of the hospital records at the two hospitals hampered our effort to characterise
      the risk of HIV infection acquisition by HCWs. Greater data completeness in
      hospital records is needed to allow the determination of the actual risk of HIV
      transmission for HCWs. To further reduce the risk of HIV infection due to
      occupational exposure, hospitals should be equipped with sufficient personal
      protective equipment (PPE) and HCWs should be reminded of the importance of
      adhering to universal precautions.

PMID- 24079807
TI  - Redox regulation of chloroplastic G6PDH activity by thioredoxin occurs through
      structural changes modifying substrate accessibility and cofactor binding.
AB  - In chloroplasts, redox regulation of enzyme activities by TRXs (thioredoxins)
      allows the co-ordination of light/dark metabolisms such as the reductive (so
      called Calvin-Benson) pathway and the OPPP (oxidative pentose phosphate pathway).
      Although the molecular mechanisms underlying the redox regulation of several TRX
      regulated enzymes have been investigated in detail, only partial information was
      available for plastidial G6PDH (glucose-6-phosphate dehydrogenase) catalysing the
      first and rate-limiting step of the OPPP. In the present study, we investigated
      changes in catalytic and structural properties undergone by G6PDH1 from
      Arabidopsis thaliana upon treatment with TRX f1, the most efficient regulator of
      the enzyme that did not show a stable interaction with its target. We found that
      the formation of the regulatory disulfide bridge that leads to activation of the
      enzyme allows better substrate accessibility to the active site and strongly
      modifies the cofactor-binding properties. Structural modelling and data from
      biochemical and biophysical studies of site-directed mutant proteins support a
      mechanism in which the positioning/function of the highly conserved Arg(131) in
      the cofactor-binding site can be directly influenced by the redox state of the
      adjacent regulatory disulfide bridge. These findings constitute another example
      of modifications to catalytic properties of a chloroplastic enzyme upon redox
      regulation, but by a mechanism unique to G6PDH.

PMID- 24079808
TI  - Chronotypes and rhythm stability in mice.
AB  - Humans come in different chronotypes: The phase of their sleep-wake cycle with
      respect to the phase of the external, sidereal cycle of night and day differs.
      Colloquially, the early chronotypes are addressed as "larks," the late ones as
      "owls." The human chronotype can be quantified in hours and minutes of local time
      by determining the median of the sleep phase. Demographically, early and late
      human chronotypes differ with respect to the stability of their rhythms and the
      prevalence of several widespread diseases and risk factors, such as depression,
      nicotine abuse, and others. Inbred mice are widely used in chronobiological
      research as model organisms, but up to now there was no way to chronotype them.
      We have developed a method to chronotype mice in hours and fractions of hours by
      measuring the median of activity (MoA) and have shown that different mouse
      strains have significantly different MoAs and, thus, chronotypes. We have further
      developed methods to estimate the stability of the behavioral rhythms and found
      that "late" mice have relatively instable rhythms. Our methods permit the use of
      inbred mice for investigations into the molecular and genetic background of the
      chronotype and the prevalence of risks and diseases that are associated with it. 

PMID- 24079809
TI  - Total synthesis of the natural product benzo[j]fluoranthene-4,9-diol: an approach
      to the synthesis of oxygenated benzo[j]fluoranthenes.
AB  - A synthetic sequence to the benzo[j]fluoranthene nucleus is described. Crucial
      steps of the procedure include a Suzuki coupling between appropriately
      substituted 2-bromo-acenaphthylene-1-carbaldehydes and 2-formylbenzeneboronates
      followed by McMurry ring closure. The synthesis represents a new approach to the
      benzo[j]fluoranthene ring system and specifically provides a method for the rapid
      preparation of differently substituted derivatives. Following this strategy, the
      first total synthesis of the recently isolated natural product
      benzo[j]fluoranthene-4,9-diol was carried out. 

PMID- 24079810
TI  - Temporalis muscle morphomics: the psoas of the craniofacial skeleton.
AB  - BACKGROUND: The psoas muscle has been shown to predict patient outcomes based on
      the quantification of muscle area using computed tomography (CT) scans. The
      accuracy of morphomic analysis on other muscles has not been clearly delineated.
      In this study, we determine the correlation between temporalis muscle mass, psoas
      muscle area, age, body mass index (BMI), and gender. METHODS: Temporalis and
      psoas muscle dimensions were determined on all trauma patients who had both
      abdominal and maxillofacial CT scans at the University of Michigan between 2004
      and 2011. Age, BMI, and gender were obtained through chart review. Univariate and
      multivariate analyses were performed to determine the relative relationship
      between morphomic data of the temporalis and psoas muscles and the ability of
      such information to correspond with clinical variables, such as BMI, age, and
      gender. RESULTS: A total of 646 patients were included in the present study.
      Among the 249 (38.5%) women and 397 (61.5%) men, the average age was 49.2 y.
      Average BMI was 27.9 kg/m2. Total psoas muscle area directly correlated with mean
      temporalis muscle thickness (r = 0.57, P < 0.001). There was an indirect
      correlation between age and psoas muscle area (r = -0.52, P < 0.001) and
      temporalis muscle thickness (r = -0.36, P < 0.001). Neither psoas nor temporalis
      measurements correlated strongly with BMI (r = 0.18, P < 0.001; r = 0.14, P =
      0.002), although stronger correlations were found in a more "frail," subgroup as
      defined by a BMI of <20 (r = 0.59, P = 0.002). CONCLUSIONS: We demonstrate that
      dimensions of the temporalis muscle can be quantified and may serve as a proxy
      for age. Going forward, we aim to assess the utility of temporalis and psoas
      morphomics in predicting complication rates among trauma patients admitted to the
      hospital to predict outcomes in the future.

PMID- 24079811
TI  - Puerarin ameliorates oxidative stress in a rodent model of traumatic brain
      injury.
AB  - BACKGROUND: A wealth of evidence has suggested that oxidative stress is involved
      in the secondary brain injury after traumatic brain injury (TBI). Recently,
      numerous in vivo and in vitro studies were reported that puerarin could inhibit
      oxidative stress through the activation of phosphatidylinositol 3-kinase (PI3K)
      Akt pathway. It is unknown, however, whether puerarin can provide neuroprotection
      and reduce oxidative stress after TBI. The present study investigated the effects
      of puerarin on the TBI-induced neurodegeneration, oxidative stress, and the
      possible role of PI3K-Akt pathway in the neuroprotection of puerarin, in a rat
      model of TBI. MATERIALS AND METHODS: Rats were randomly distributed into various
      subgroups undergoing the sham surgery or TBI procedures. Puerarin (200 mg/kg) was
      given intraperitoneally at 10 min before injury and PI3K-Akt pathway inhibitor
      LY294002 was also administered intracerebroventricular in one subgroup. All rats
      were killed at 24 h after TBI for examination. RESULTS: Our data indicated that
      puerarin could significantly reduce TBI-induced neuronal degeneration,
      accompanied by the partial restoration of the redox disturbance and enhanced
      expression of phospho-Akt in the pericontusional cortex after TBI. Moreover, PI3K
      Akt pathway inhibitor LY294002 could partially abrogate the neuroprotection of
      puerarin in rats with TBI. CONCLUSIONS: These results indicate that puerarin can
      ameliorate oxidative neurodegeneration after TBI, at least in part, through the
      activation of PI3K-Akt pathway.

PMID- 24079812
TI  - CCN2 is transiently expressed by keratinocytes during re-epithelialization and
      regulates keratinocyte migration in vitro by the ras-MEK-ERK signaling pathway.
AB  - BACKGROUND: CCN2 (previously known as connective tissue growth factor) is a
      multifunctional matricellular protein that has numerous effects on cell life and
      cell interactions with the connective tissue. Although the importance of CCN2 for
      the fibrotic process in wound healing has been well studied, the involvement of
      CCN2 in keratinocyte function has not yet been explored. Therefore, the aim of
      the present study was to investigate the role of CCN2 in the epidermis during
      wound healing. MATERIALS AND METHODS: Immunohistochemistry was done on sections
      from full-thickness porcine wounds. The effect of CCN2 on the migration of
      cultured human keratinocytes exposed to scratch wounds, the effect on
      phosphorylation of extracellular signal-related kinases (ERK), and the effect of
      adding inhibitors to the ERK/mitogen-activated protein kinase pathway to human
      keratinocytes were studied. RESULTS: The CCN2 protein was transiently expressed
      in vivo at the leading keratinocyte edge during re-epithelialization of full
      thickness porcine wounds. In vitro, exogenous addition of CCN2 to human
      keratinocyte cultures regulated keratinocyte migration and resulted in
      phosphorylation of ERK. The addition of inhibitors of ERK/mitogen-activated
      protein kinase counteracted the effect of CCN2 on migration. CONCLUSIONS: CCN2
      was transiently expressed at the leading keratinocyte edge in vivo. The biologic
      importance of this was supported in vitro, because CCN2 regulated human
      keratinocyte migration through activation of the Ras-mitogen-activated protein
      kinase kinase-ERK signal transduction pathway.

PMID- 24079813
TI  - Tuning cofactor redox potentials: the 2-methoxy dihedral angle generates a redox
      potential difference of >160 mV between the primary (Q(A)) and secondary (Q(B))
      quinones of the bacterial photosynthetic reaction center.
AB  - Only quinones with a 2-methoxy group can act simultaneously as the primary (QA)
      and secondary (QB) electron acceptors in photosynthetic reaction centers from
      Rhodobacter sphaeroides. (13)C hyperfine sublevel correlation measurements of the
      2-methoxy in the semiquinone states, SQA and SQB, were compared with quantum
      mechanics calculations of the (13)C couplings as a function of the dihedral
      angle. X-ray structures support dihedral angle assignments corresponding to a
      redox potential gap (DeltaEm) between QA and QB of ~180 mV. This is consistent
      with the failure of a ubiquinone analogue lacking the 2-methoxy to function as QB
      in mutant reaction centers with a DeltaEm of ~160-195 mV.

PMID- 24079814
TI  - Multi-degree of freedom joystick for virtual reality simulation.
AB  - A modular control interface and simulated virtual reality environment were
      designed and created in order to determine how the kinematic architecture of a
      control interface affects minimally invasive surgery training. A user is able to
      selectively determine the kinematic configuration of an input device (number,
      type and location of degrees of freedom) for a specific surgical simulation
      through the use of modular joints and constraint components. Furthermore, passive
      locking was designed and implemented through the use of inflated latex tubing
      around rotational joints in order to allow a user to step away from a simulation
      without unwanted tool motion. It is believed that these features will facilitate
      improved simulation of a variety of surgical procedures and, thus, improve
      surgical skills training.

PMID- 24079815
TI  - Community-based participatory research to decrease smoking prevalence in a high
      risk young adult population: an evaluation of the Students Against Nicotine and
      Tobacco Addiction (SANTA) project.
AB  - Students Against Nicotine and Tobacco Addiction is a community-based
      participatory research project that engages local medical and mental health
      providers in partnership with students, teachers, and administrators at the
      Minnesota-based Job Corps. This intervention contains multiple and synchronous
      elements designed to allay the stress that students attribute to smoking,
      including physical activities, nonphysical activities, purposeful modifications
      to the campus's environment and rules/policies, and on-site smoking cessation
      education and peer support. The intent of the present investigation was to
      evaluate (a) the types of stress most predictive of smoking behavior and/or
      nicotine dependence, (b) which activities students are participating in, and (c)
      which activities are most predictive of behavior change (or readiness to change).
      Quantitative data were collected through 5 campus-wide surveys. Response rates
      for each survey exceeded 85%. Stressors most commonly cited included struggles to
      find a job, financial problems, family conflict, lack of privacy or freedom,
      missing family or being homesick, dealing with Job Corps rules, and other
      unspecified. The most popular activities in which students took part were
      physically active ones. However, activities most predictive of beneficent change
      were nonphysical. Approximately one third of respondents were nicotine dependent
      at baseline. Nearly half intended to quit within 1 month and 74% intended to quit
      within 6 months. Interventions perceived as most helpful toward reducing smoking
      were nonphysical in nature. Future efforts with this and comparable populations
      should engage youth in advancing such activities within a broader range of
      activity choices, alongside conventional education and support.

PMID- 24079816
TI  - Affinity comparison of p3 and p8 peptide displaying bacteriophages using surface
      plasmon resonance.
AB  - Ever increasing demands in sensitivity and specificity of biosensors have
      recently established a trend toward the use of multivalent bioreceptors. This
      trend has also been introduced in the field of bacteriophage affinity peptides,
      where the entire phage is used as a receptor rather than the individual peptides.
      Although this approach is gaining in popularity due to the numerous advantages,
      binding kinetics of complete phage particles have never been studied in detail,
      notwithstanding being essential for the efficient design of such applications. In
      this paper we used an in house developed fiber-optic surface plasmon resonance
      (FO-SPR) biosensor to study the affinity and binding kinetics of phages,
      displaying peptide libraries. By using either peptide expression on the p3 or on
      the p8 coat proteins, a corresponding density of 5 up to more than 2000 peptides
      on a single virus particle was obtained. Binding parameters of 26 different
      filamentous phages, displaying peptides selective for enhanced Green Fluorescent
      Protein (eGFP), were characterized. This study revealed a broad affinity range of
      phages for the target eGFP, indicating their potential to be used for
      applications with different requirements in binding kinetics. Moreover, detailed
      analysis of koff and kon values of several selected p3 and p8 phages, using the
      FO-SPR biosensor, clearly showed the correlation between the binding parameters
      and the density at which eGFP-peptides are being expressed. Consequently,
      although p3 and p8-based phages both revealed exceptionally high affinities for
      eGFP, two p8 phages were found to have the highest affinity with dissociation
      constants (Kd) in the femtomolar range. 

PMID- 24079817
TI  - Validation of the allergic rhinitis treatment satisfaction and preference scale.
AB  - Allergic rhinitis (AR) affects 7.8% of U.S. adults and 10-30% of the population
      worldwide. AR symptoms (rhinorrhea, congestion, sneezing, nasal/ocular pruritus,
      and postnasal drainage) significantly impact sleep and reduce cognitive and
      emotional functioning affecting work and school productivity. Although effective,
      intranasal corticoid (INS) steroid delivery systems are often associated with
      adverse sensory attributes, affecting patient adherence and reducing efficacy.
      Patient satisfaction with treatment characteristics predicts adherence levels
      that can better inform treatment decisions. This study was designed to evaluate
      psychometric evidence for the self-administered Allergic Rhinitis Treatment
      Satisfaction and Preference (ARTSP) scale as a patient-reported outcomes measure
      for use in clinical research. Analytic methods included qualitative analysis of
      patient focus groups and psychometric analysis of scale data collected from 185
      AR subjects enrolled in a randomized, 2-week, crossover, comparative U.S.
      clinical trial. Qualitative analysis conceptually supported nine treatment
      satisfaction subscales. Reliability by Cronbach alpha met accepted standards.
      Evidence was found for construct validity using structural equation modeling,
      criterion validity from correlation patterns between treatment satisfaction and
      health-related quality of life scales, and discriminant validity analysis based
      on AR symptom-defined groups. Responsiveness was shown by significant change in
      treatment satisfaction subscales among AR symptom change groups. Scores on
      treatment preference items discriminated between the aqueous and aerosol INS
      formulations. The ARTSP scale is a conceptually sound, reliable, valid, and
      responsive measure of patient evaluations of alternative therapies, providing
      detailed information about treatment characteristics that are likely to influence
      adherence levels and subsequent AR clinical control. 

PMID- 24079819
TI  - Enantioselective intermolecular [2+2] photocycloadditions of isoquinolone
      mediated by a chiral hydrogen-bonding template.
AB  - The first examples of enantioselective intermolecular [2+2] photocycloadditions
      of isoquinolone with alkenes are reported. Photoreactions were carried out at low
      temperature in the presence of a chiral hydrogen-bonding template, which
      effectively shields one face of the substrate through formation of a hydrogen
      bonded supramolecular complex. Functionalized cyclobutane products were obtained
      in excellent yields (86-98%) and with outstanding regio-, diastereo-, and
      enantioselectivity (88-99% ee). 

PMID- 24079818
TI  - Identification of GABA(C) receptor protein homeostasis network components from
      three tandem mass spectrometry proteomics approaches.
AB  - gamma-Amino butyric acid type C (GABA(C)) receptors inhibit neuronal firing
      primarily in retina. Maintenance of GABA(C) receptor protein homeostasis in cells
      is essential for its function. However, a systematic study of GABA(C) receptor
      protein homeostasis (proteostasis) network components is absent. Here
      coimmunoprecipitation of human GABA(C)-rho1-receptor complexes was performed in
      HEK293 cells overexpressing rho1 receptors. To enhance the coverage and
      reliability of identified proteins, immunoisolated rho1-receptor complexes were
      subjected to three tandem mass spectrometry (MS)-based proteomic analyses,
      namely, gel-based tandem MS (GeLC-MS/MS), solution-based tandem MS (SoLC-MS/MS),
      and multidimensional protein identification technology (MudPIT). From the 107
      identified proteins, we assembled GABA(C)-rho1-receptor proteostasis network
      components, including proteins with protein folding, degradation, and trafficking
      functions. We studied representative individual rho1-receptor-interacting
      proteins, including calnexin, a lectin chaperone that facilitates glycoprotein
      folding, and LMAN1, a glycoprotein trafficking receptor, and global effectors
      that regulate protein folding in cells based on bioinformatics analysis,
      including HSF1, a master regulator of the heat shock response, and XBP1, a key
      transcription factor of the unfolded protein response. Manipulating selected
      GABA(C) receptor proteostasis network components is a promising strategy to
      regulate GABA(C) receptor folding, trafficking, degradation and thus function to
      ameliorate related retinal diseases.

PMID- 24079820
TI  - Use of 2'-spirocyclic ethers in HCV nucleoside design.
AB  - Conformationally restricted 2'-spironucleosides and their prodrugs were
      synthesized as potential anti-HCV agents. Although the replicon activity of the
      new agents containing pyrimidine bases was modest, the triphosphate of a 2'
      oxetane cytidine analogue demonstrated potent intrinsic biochemical activity
      against the NS5B polymerase, with IC50 = 8.48 MUM. Activity against NS5B bearing
      the S282T mutation was reduced. Phosphoramidate prodrugs of a 2'-oxetane 2-amino
      6-O-methyl-purine nucleoside demonstrated potent anti-HCV activity in vitro, and
      the corresponding triphosphate retained similar potent activity against both wild
      type and S282T HCV NS5B polymerase. 

PMID- 24079821
TI  - Influence of solution chemistry on the release of multiwalled carbon nanotubes
      from silica surfaces.
AB  - The release of multiwalled carbon nanotubes (MWNTs) that were deposited on silica
      surfaces was investigated using a quartz crystal microbalance with dissipation
      monitoring (QCM-D). MWNTs were deposited on silica surfaces at elevated NaCl and
      CaCl2 concentrations before being rinsed with eluents of different solution
      chemistries to induce their remobilization. Energetically speaking, the MWNTs
      were released from the primary energy minimum when the background NaCl or CaCl2
      concentrations were decreased at pH 7.1. The increase in electrostatic repulsion
      between MWNTs and silica likely caused a reduction in the energy barrier, which
      enabled the release of MWNTs. The degree of release increased in a stepwise
      fashion when the nanotubes were sequentially exposed to eluents of decreasing
      electrolyte concentrations, possibly due to the heterogeneity in nanotube surface
      charge densities. The degree of release via a successive reduction in NaCl
      concentration was lower at pH 4.0 than at 7.1 due to MWNTs and silica surfaces
      exhibiting a less negative surface charge at pH 4.0. Most of the deposited MWNTs
      were released when the pH was decreased from 7.1 to 4.0 at 1.5 mM CaCl2. This was
      attributed to the elimination of calcium bridging between the carboxyl groups on
      MWNTs and silanol groups on silica surfaces. 

PMID- 24079822
TI  - Short term and long term results after open vs. laparoscopic appendectomy in
      childhood and adolescence: a subgroup analysis.
AB  - BACKGROUND: A comparative study was performed to compare quality of life after
      laparoscopic and open appendectomy in children and adolescents in a German
      General Hospital. The same study population was re-evaluated regarding their
      quality of life several years after operation. METHODS: Children and adolescents
      (n = 158) who underwent appendectomy for acute appendicitis between 1999 and 2001
      were retrospectively analysed. Seven years after surgery those patients were
      interviewed applying a SF-36 questionnaire regarding their quality of life.
      RESULTS: For short term outcomes there was a trend towards reduced specific
      postoperative complications in the laparoscopically operated group (9.3 vs.
      10.7%). Significantly more patients in the laparoscopic group would recommend the
      operation procedure to family members or friends than in the open group. Among
      the evaluated patients there was a significantly higher satisfaction concerning
      size and appearance of their scars in the laparoscopic group. The results of the
      evaluation in the eight categories of the SF-36 showed similar results in both
      groups. CONCLUSIONS: More patients with laparoscopic appendectomy appeared to be
      satisfied with their operation method as becomes evident by a higher
      recommendation rate and a higher satisfaction concerning their scars.

PMID- 24079823
TI  - The efficacy and safety of electroacupuncture for women with pure stress urinary
      incontinence: study protocol for a multicenter randomized controlled trial.
AB  - BACKGROUND: Although available evidence relating to its effectiveness is weak,
      acupuncture is used as an alternative therapy for stress urinary incontinence. We
      report a protocol of a randomized controlled trial using electroacupuncture (the
      passing of a weak current between inserted acupuncture needles) to treat women
      with pure stress urinary incontinence. METHODS/DESIGN: This is a large-scale
      multicenter subject-blinded randomized controlled trial. A total of 500 women
      with pure stress urinary incontinence will be randomly assigned to two groups: a
      treatment group and a control group. The treatment group will receive
      electroacupuncture with deep needling at acupuncture points BL33 and BL35. The
      control group will receive sham electroacupuncture with non-penetrating needling
      at sham locations for the acupuncture points of BL33 and BL35. Participants will
      be given three sessions a week for 6 weeks. A 24-week-long follow-up will be
      conducted. The primary outcome will be the change in amount of urine leakage at
      the sixth week from a baseline measured by a 1-h pad test. The secondary outcomes
      include: the 72-h incontinence episode frequency based on a 72-h bladder diary;
      the score of International Consultation on Incontinence Questionnaire-Urinary
      Incontinence Short Form; the degree of urinary incontinence based on a 72-h
      bladder diary; self-assessment of the therapeutic effect; weekly consumption of
      pads; application of other treatments for stress urinary incontinence; and
      subgroup analysis stratified by incontinence severity. The safety of
      electroacupuncture will also be assessed. DISCUSSION: This trial will help to
      identify whether electroacupuncture is effective for stress urinary incontinence,
      and, if so, whether it is a therapeutic effect rather than a placebo effect.
      TRIAL REGISTRATION: Clinical Trials.gov NCT01784172.

PMID- 24079824
TI  - Cytotoxicity of naturally occurring rhamnofolane diterpenes from Jatropha curcas.
AB  - Twelve rhamnofolane diterpenoids, including curcusecons A-E with unusual seco
      rhamnofolane skeletons, curcusones F-J, 4-epi-curcusone E, and 3-dehydroxy-2-epi
      caniojane, together with seven known analogues, curcusones A-E, jatrogrossidione,
      and 2-epi-jatrogrossidione, were isolated from the roots of Jatropha curcas.
      Their structures were determined by extensive spectroscopic methods, and the
      relative stereochemistry of curcusecon B was further confirmed by X-ray
      crystallographic data. Their cytotoxity against five human cancer cells was
      studied and the results indicated that the dienone system in ring B was essential
      for cytotoxicity of these compounds. 

PMID- 24079825
TI  - Outcomes after treatment of acute aortic occlusion.
AB  - INTRODUCTION: Acute aortic occlusion (AAO) is a rare disease with high morbidity
      and mortality. The aim of this study was to describe the results of surgical
      treatment of acute aortic occlusion and risk factors for mortality. METHODS:
      Retrospective review of the clinical history of 29 patients diagnosed and
      operated on for AAO during 28 years. The following variables were analysed: age,
      sex, tabaco use, diabetes, chronic renal insufficiency, chronic heart failure,
      atrial fibrillation, arterial hypertension, symptoms, diagnosis and treatment, 30
      day mortality and long-term survival. A univariant analysis was performed of
      variables related to mortality. RESULTS: Twenty-nine patients were included (18
      male) with a mean age of 66,2 years. The aetiology was: embolism (EM) in 11 cases
      and Thrombosis (TR) in 18 cases. The surgical procedures performed included
      bilateral transfemoral thrombectomy (14 cases), aorto-bifemoral by-pass (8
      cases), axilo uni/bifemoral by-pass (5 cases) and aortoiliac and renal
      tromboendarterectomy (2 cases). Morbidity included: renal failure (14 cases),
      mesenteric ischemia (4 cases), cardiac complications (7 cases), respiratory
      complications (5 cases) and loss of extremity (2 cases). The in-hospital
      mortality was 21% (EM 0%, TR 21%). The estimated survival at 1.3 and 5 years was
      60, 50 and 44% respectively. Age (p=0.032), arterial hypertension (p=0.039) and
      aetiology of the AAO (p=0.039) were related to mortality. CONCLUSIONS: Acute
      aortic occlusion is a medical emergency with high mortality rates. Acute renal
      failure is the most common postoperative complication.

PMID- 24079826
TI  - Facile fabrication of biocompatible and tunable multifunctional nanomaterials via
      iron-mediated atom transfer radical polymerization with activators generated by
      electron transfer.
AB  - A novel strategy of preparing multifunctional nanoparticles (NPs) with near infra
      red (NIR) fluorescence and magnetism showing good hydrophilicity and low toxicity
      was developed via surface-initiated atom transfer radical polymerization with
      activators generated by electron transfer (AGET ATRP) of poly(ethylene glycol)
      monomethyl ether methacrylate (PEGMA) and glycidyl methacrylate (GMA) employing
      biocompatible iron as the catalyst on the surface of silica coated iron oxide
      (Fe3O4@SiO2) NPs. The small molecules (CS2), a NIR fluorescent chromophore, can
      be fixed into the covalently grafted polymer shell of the NPs by chemical
      reaction through a covalent bond to obtain stable CS2 dotted NPs
      Fe3O4@SiO2@PPEGMA-co-PGMA@CS2. The fluorescence intensity of the as-prepared NPs
      could be conveniently regulated by altering the silica shell thickness (varying
      the feed of silica source TEOS), CS2 feed, or the feed ratio of VPEGMA/VGMA,
      which are easily realized in the preparation process. Thorough investigation of
      the properties of the final NPs including in vivo dual modal imaging indicate
      that such NPs are one of the competitive candidates as imaging agents proving a
      promising potential in the biomedical area. 

PMID- 24079829
TI  - Mechanisms of eukaryotic transcription.
AB  - A report on the Cold Spring Harbor Laboratory Mechanisms of Eukaryotic
      Transcription meeting, Cold Spring Harbor, New York, USA, August 27-31, 2013.

PMID- 24079827
TI  - Comparison of RNA- or LNA-hybrid oligonucleotides in template-switching reactions
      for high-speed sequencing library preparation.
AB  - BACKGROUND: Analyzing the RNA pool or transcription start sites requires
      effective means to convert RNA into cDNA libraries for digital expression
      counting. With current high-speed sequencers, it is necessary to flank the cDNAs
      with specific adapters. Adding template-switching oligonucleotides to reverse
      transcription reactions is the most commonly used approach when working with very
      small quantities of RNA even from single cells. RESULTS: Here we compared the
      performance of DNA-RNA, DNA-LNA and DNA oligonucleotides in template-switching
      during nanoCAGE library preparation. Test libraries from rat muscle and HeLa cell
      RNA were prepared in technical triplicates and sequenced for comparison of the
      gene coverage and distribution of the reads within transcripts. The DNA-RNA
      oligonucleotide showed the highest specificity for capped 5' ends of mRNA,
      whereas the DNA-LNA provided similar gene coverage with more reads falling within
      exons. CONCLUSIONS: While confirming the cap-specific preference of DNA-RNA
      oligonucleotides in template-switching reactions, our data indicate that DNA-LNA
      hybrid oligonucleotides could potentially find other applications in random RNA
      sequencing.

PMID- 24079830
TI  - Quantitative imaging of the electrostatic field and potential generated by a
      transmembrane protein pore at subnanometer resolution.
AB  - Elucidating the mechanisms by which proteins translocate small molecules and ions
      through transmembrane pores and channels is of great interest in biology,
      medicine, and nanotechnology. However, the characterization of pore forming
      proteins in their native state lacks suitable methods that are capable of high
      resolution imaging (~1 nm) while simultaneously mapping physical and chemical
      properties. Here we report how force-distance (FD) curve-based atomic force
      microscopy (AFM) imaging can be applied to image the native pore forming outer
      membrane protein F (OmpF) at subnanometer resolution and to quantify the
      electrostatic field and potential generated by the transmembrane pore. We further
      observe the electrostatic field and potential of the OmpF pore switching "on" and
      "off" in dependence of the electrolyte concentration. Because electrostatic field
      and potential select for charged molecules and ions and guide them to the
      transmembrane pore the insights are of fundamental importance to understand the
      pore function. These experimental results establish FD-based AFM as a unique tool
      to image biological systems to subnanometer resolution and to quantify their
      electrostatic properties.

PMID- 24079831
TI  - Enhanced stability of monomer fold correlates with extreme drug resistance of HIV
      1 protease.
AB  - During treatment, mutations in HIV-1 protease (PR) are selected rapidly that
      confer resistance by decreasing affinity to clinical protease inhibitors (PIs).
      As these unique drug resistance mutations can compromise the fitness of the virus
      to replicate, mutations that restore conformational stability and activity while
      retaining drug resistance are selected on further evolution. Here we identify
      several compensating mechanisms by which an extreme drug-resistant mutant bearing
      20 mutations (PR20) with >5-fold increased Kd and >4000-fold decreased affinity
      to the PI darunavir functions. (1) PR20 cleaves, albeit poorly, Gag polyprotein
      substrates essential for viral maturation. (2) PR20 dimer, which exhibits
      distinctly enhanced thermal stability, has highly attenuated autoproteolysis,
      thus likely prolonging its lifetime in vivo. (3) The enhanced stability of PR20
      results from stabilization of the monomer fold. Both monomeric PR20(T26A) and
      dimeric PR20 exhibit Tm values 6-7.5  degrees C higher than those for their PR
      counterparts. Two specific mutations in PR20, L33F and L63P at sites of
      autoproteolysis, increase the Tm of monomeric PR(T26A) by ~8  degrees C, similar
      to PR20(T26A). However, without other compensatory mutations as seen in PR20,
      L33F and L63P substitutions, together, neither restrict autoproteolysis nor
      significantly reduce binding affinity to darunavir. To determine whether dimer
      stability contributes to binding affinity for inhibitors, we examined single
      chain dimers of PR and PR(D25N) in which the corresponding identical monomer
      units were covalently linked by GGSSG sequence. Linking of the subunits did not
      appreciably change the DeltaTm on inhibitor binding; thus stabilization by
      tethering appears to have little direct effect on enhancing inhibitor affinity.

PMID- 24079832
TI  - How does the metabolism of tumour cells differ from that of normal cells.
AB  - Tumour cells thrive in environments that would be hostile to their normal cell
      counterparts. Survival depends on the selection of cell lines that harbour
      modifications of both, gene regulation that shifts the balance between the cell
      cycle and apoptosis and those that involve the plasticity of the metabolic
      machinery. With regards to metabolism, the selected phenotypes usually display
      enhanced anaerobic glycolysis even in the presence of oxygen, the so-called
      Warburg effect, and anabolic pathways that provide precursors for the synthesis
      of lipids, proteins and DNA. The review will discuss the original ideas of Otto
      Warburg and how they initially led to the notion that mitochondria of tumour
      cells were dysfunctional. Data will be presented to show that not only the
      organelles are viable and respiring, but that they are key players in
      tumorigenesis and metastasis. Likewise, interconnecting pathways that stand out
      in the tumour phenotype and that require intact mitochondria such as
      glutaminolysis will be addressed. Furthermore, comments will be made as to how
      the peculiarities of the biochemistry of tumour cells renders them amenable to
      new forms of treatment by highlighting possible targets for inhibitors. In this
      respect, a case study describing the effect of a metabolite analogue, the
      alkylating agent 3BP (3-bromopyruvate), on glycolytic enzyme targets will be
      presented. 

PMID- 24079834
TI  - Case series and literature review of multiple nodular sarcoidosis.
AB  - BACKGROUND: Nodular lung disease is a rare presentation of sarcoidosis.
      Radiologically it can present as multiple pulmonary masses or solitary lung
      nodule. CASE PRESENTATION: We report three cases of nodular sarcoidosis in young
      females of Asian origin who had initially presented with dry cough and worsening
      dyspnea non-responsive to initially administered antibiotics. Pulmonary nodules
      were discovered upon radiographic imaging in all three cases which raised concern
      for the possibility of neoplastic processes. Subsequent biopsies revealed
      granulomatous inflammation indicative of sarcoidosis. All cases responded very
      well to systemic corticosteroids. CONCLUSION: Sarcoidosis may present as nodular
      infiltrates which alerts the treating physician to other neoplastic and
      infectious diseases of the lungs. Appropriate workup may reveal the true nature
      of this disease and hence, simplify treatment.

PMID- 24079835
TI  - The management of breakthrough cancer pain--educational needs a European nursing
      survey.
AB  - Poorly managed cancer pain is well known to profoundly impact the patient's daily
      life and interfere with quality of life. Nurses who cared for patients with
      cancer from 12 European countries participated in a survey of breakthrough cancer
      pain practice. The purpose was to investigate how nurses assess breakthrough
      cancer pain, use of standardised tools, confidence in supporting patients and
      awareness of medications. Responses from 1241 participants showed country
      variations. The majority of the sample was female, Germany had the highest
      proportion of male nurses (21.0%), followed by Greece (15.8%). A significantly
      larger proportion of nurses with longer experience and more education (78.8%)
      used a comprehensive definition of breakthrough cancer pain. Significant
      variations in training were found; 71% of Finnish nurses had received training
      compared with 6% of Greek nurses. Training and using a standardised assessment
      tool was associated with a significant increase in the nurses' perceived ability
      to distinguish between breakthrough and background pain. Nurses in countries with
      the highest proportion of training were most confident in supporting patients. In
      conclusion, there still exists problems with effective management of patients'
      breakthrough cancer pain, continuing inability to define the difference between
      background and breakthrough cancer pain leads to poor treatment. 

PMID- 24079836
TI  - Potassium tert-butoxide promoted annulation of 2-alkynylphenyl propargyl ethers:
      selective synthesis of benzofuran and 12H-benzoannulene derivatives.
AB  - We present here our results on potassium tert-butoxide promoted annulation
      reactions of 2-alkynylphenyl propargyl ethers to give two different types of
      heterocycles: 3-benzyl-2-alkynylbenzofurans and 12H-benzoannulenbenzo[b]furans. A
      series of functionalized 2-alkynylphenyl propargyl ethers were efficiently
      cyclized by potassium tert-butoxide to the corresponding products. The optimized
      reaction conditions tolerated a large variety of functional groups, including
      electron-rich, electron-poor, and N-heterocyclic substrates. Selective product
      formation was obtained by controlling the solvent and temperature. When THF was
      used at room temperature, 3-benzyl-2-alkynylbenzofuran derivatives were
      exclusively obtained, while the use of DMF at 60  degrees C gave selectively 12H
      benzoannulen[b]benzofurans. 

PMID- 24079833
TI  - MicroRNAs in cancer.
AB  - MicroRNAs (miRNAs) are small noncoding RNAs that typically inhibit the
      translation and stability of messenger RNAs (mRNAs), controlling genes involved
      in cellular processes such as inflammation, cell-cycle regulation, stress
      response, differentiation, apoptosis, and migration. Thus, miRNAs have been
      implicated in the regulation of virtually all signaling circuits within a cell,
      and their dysregulation has been shown to play an essential role in the
      development and progression of cancer. Here, after a brief description of miRNA
      genomics, biogenesis, and function, we discuss the effects of miRNA dysregulation
      in the cellular pathways that lead to the progressive conversion of normal cells
      into cancer cells and the potential to develop new molecular miRNA-targeted
      therapies. 

PMID- 24079837
TI  - Numerical modeling of the releases of (90)SR from Fukushima to the ocean: an
      evaluation of the source term.
AB  - A numerical model consisting of a 3D advection/diffusion equation, including
      uptake/release reactions between water and sediments described in a dynamic way,
      has been applied to simulate the marine releases of (90)Sr from the Fukushima
      power plant after the March 2011 tsunami. This is a relevant issue since (90)Sr
      releases are still occurring. The model used here had been successfully applied
      to simulate (137)Cs releases. Assuming that the temporal trend of (90)Sr releases
      was the same as for (137)Cs during the four months after the accident simulated
      here, the source term could be evaluated, resulting in a total release of 80 TBq
      of (90)Sr until the end of June, which is in the lower range of previous
      estimates. Computed vertical profiles of (90)Sr in the water column have been
      compared with measured ones. The (90)Sr inventories within the model domain have
      also been calculated for the water column and for bed sediments. Maximum
      dissolved inventory (obtained for April 10th, 2011) within the model domain
      results in about 58 TBq. Inventories in bed sediments are 3 orders of magnitude
      lower than in the water column due to the low reactivity of this radionuclide.
      (90)Sr/(137)Cs ratios in the ocean have also been calculated and compared with
      measured values, showing both spatial and temporal variations. 

PMID- 24079838
TI  - Economic evaluation alongside a single RCT of an integrative psychotherapeutic
      nursing home programme.
AB  - BACKGROUND: There is an 80% prevalence of two or more psychiatric symptoms in
      psychogeriatric patients. Multiple psychiatric symptoms (MPS) have many negative
      effects on quality of life of the patient as well as on caregiver burden and
      competence. Irrespective of the effectiveness of an intervention programme, it is
      important to take into account its economic aspects. METHODS: The economic
      evaluation was performed alongside a single open RCT and conducted between 2001
      and 2006. The patients who met the selection criteria were asked to participate
      in the RCT. After the patient or his caregiver signed a written informed consent
      form, he was then randomly assigned to either IRR or UC.The costs and effects of
      IRR were compared to those of UC. We assessed the cost-utility of IRR as well as
      the cost-effectiveness of both conditions. Primary outcome variable: severity of
      MPS (NPI) of patients; secondary outcome variables: general caregiver burden (CB)
      and caregiver competence (CCL), quality of life (EQ5D) of the patient, and total
      medical costs per patient (TiC-P). Cost-utility was evaluated on the basis of
      differences in total medical costs). Cost-effectiveness was evaluated by
      comparing differences of total medical costs and effects on NPI, CB and CCL
      (Incremental Cost-Effectiveness Ratio: ICER). CEAC-analyses were performed for
      QALY and NPI-severity. All significant testing was fixed at p<0.05 (two-tailed).
      The data were analyzed according to the intention-to-treat (ITT)-principle. A
      complete cases approach (CC) was used. RESULTS: IRR turned out to be non
      significantly, 10.5% more expensive than UC (? 36 per day). The number of QALYs
      was 0.01 higher (non-significant) in IRR, resulting in ? 276,290 per QALY.
      According to the ICER-method, IRR was significantly more cost-effective on NPI
      sum-severity of the patient (up to 34%), CB and CCL (up to 50%), with ICERs
      varying from ? 130 to ? 540 per additional point of improvement. CONCLUSIONS: No
      significant differences were found on QALYs. In IRR patients improved
      significantly more on severity of MPS, and caregivers on general burden and
      competence, with incremental costs varying from ? 130 to ? 540 per additional
      point of improvement. The surplus costs of IRR are considered acceptable, taking
      into account the high societal costs of suffering from MPS of psychogeriatric
      patients and the high burden of caregivers. The large discrepancy in economic
      evaluation between QALYs (based on EQ5D) and ICERs (based on clinically relevant
      outcomes) demands further research on the validity of EQ5D in psychogeriatric
      cost-utility studies. (Trial registration nr.: ISRCTN 38916563; December 2004).

PMID- 24079839
TI  - Effect of rCaIFN-gamma on NK cytotoxic activity in the peripheral blood of dogs.
AB  - Previously, the ability of interferon (IFN) to reinforce antitumor immune
      capacity has received much attention. In humans and mice, natural killer (NK)
      cells are activated by IFN, thereby reinforcing antitumor immunity. We
      investigated whether NK cytotoxic activity can be enhanced by recombinant canine
      interferon-gamma (rCaIFN-gamma) in dogs. First, we investigated the effects of
      various concentrations of and time exposures to IFN-gamma in the culture medium
      on the NK cytotoxic activity of peripheral blood lymphocyte (PBLs) extracted from
      healthy beagles. Time- and concentration-dependent enhancement of NK cytotoxic
      activity of PBLs was observed. We then investigated whether the NK cytotoxic
      activity of PBLs is enhanced 24h after administration of rCaIFN-gamma (10,000
      units/kg body weight) in healthy beagles. Our in vivo study confirmed that NK
      cytotoxic activity of PBLs was enhanced by this approach, suggesting that
      antitumor immunity was reinforced. In dogs, rCaIFN-gamma may be effective for
      bolstering antitumor immune capacity.

PMID- 24079840
TI  - Regulatory T cells, Cytotoxic T lymphocytes and a T(H)1 cytokine profile in dogs
      naturally infected by Leishmania infantum.
AB  - Canine leishmaniasis caused by the protozoan parasite Leishmania infantum is a
      chronic systemic disease endemic in Mediterranean basin. The aim of the study is
      to investigate the immune profile of dogs naturally infected by Leishmania
      infantum. In order to address such issue, CD4(+) and CD8(+) lymphocyte T cell
      subsets, peripheral CD4(+)CD3(+)Foxp3(+) (Treg) levels and the presence of pro
      inflammatory T cells have been assessed, in 45 infected dogs and in 30 healthy
      animals, by using immunofluorescence and flow cytometry detection. Animals were
      categorised according to their clinical-pathological status and their antibody
      titer at diagnosis. Results showing a significant increase of CD8(+)CD3(+) T
      lymphocytes, a reduced percentage of the T regulatory CD4(+)CD3(+)Foxp3(+) subset
      and a significant increase of T(H)1 cells, characterise the infected dogs,
      regardless of their antibody titer or the occurrence of clinical symptomatic
      disease. These data may provide new insights into the pathogenesis of immune
      mediated alterations associated with canine leishmaniasis.

PMID- 24079841
TI  - Herd-level risk factors for bovine viral diarrhea virus infection in dairy herds
      from Southern Brazil.
AB  - A cross-sectional study was carried out to identify risk factors for bovine viral
      diarrhea virus (BVDV) infection in 300 randomly selected dairy herds which were
      tested for antibodies in bulk tank milk (BTM) using a commercial indirect ELISA
      kit (SVANOVA). Results from the analysis were interpreted according to the
      Swedish BVDV control scheme. The testing revealed 129 (43%) BTM BVDV antibody
      positive herds. Use of artificial insemination (AI) and herd size were
      significantly associated with BVDV serological status (P<0.05). Dairy herds that
      use AI had 2.82 increased odds of BVDV-seropositivity (95% CI: 1.02-7.24). Since
      the semen used in the studied population come from known selected sires, it was
      hypothesized that AI technicians should represent an important risk factor
      because the increasing number of visitors in the farm can introduce the virus
      through the clothes, shoes and contaminated equipment. 

PMID- 24079842
TI  - Economic evaluation of continuous subcutaneous insulin infusion for children with
      diabetes - a pilot study: CSII application for children - economic evaluation.
AB  - BACKGROUND: The objective of this study is to assess the cost of using continuous
      subcutaneous insulin infusion to treat children with type-1diabetes in Bulgaria,
      considering changes in body mass index (BMI) and the glycated hemoglobin. The
      study was performed from the perspective of the Bulgarian National Health
      Insurance Fund (NHIF) and patients. METHODS: A total of 34 pediatric type-1
      diabetes patients were observed for 7 months, divided into 2 groups - on pumps
      and on insulin analogue therapy. Patient demographic data, BMI and glycated
      hemoglobin level were obtained and recorded. The cost of insulin, pumps, and
      consumables were calculated and compared with changes in glycated hemoglobin
      level. The incremental cost-effectiveness ratio was below the threshold value of
      gross domestic product per capita. RESULTS: The results were sensitive to changes
      in glycated hemoglobin level. Improvements associated with glycemic control led
      to a reduced glycated hemoglobin level that could ensure good diabetes
      management, but its influence on BMI in growing children remains unclear.
      CONCLUSION: Continuous subcutaneous insulin infusion appears to be more cost
      effective for the Bulgarian pediatric population and health care system.

PMID- 24079843
TI  - The prevalence and genetics of Parkinson's disease in sub-Saharan Africans.
AB  - Parkinson's disease (PD) is under-studied in Black Sub-Saharan African (SSA)
      populations. To date, there have been only six prevalence and no incidence
      studies. The crude prevalence of PD in SSA varies from 7 to 20 per 100,000, which
      is appreciably lower than in Caucasian populations. There are a limited number of
      published studies (nine) on the genetic factors associated with PD in SSA
      populations. Mutations have been reported in the parkin gene, and are restricted
      to only three patients (two Black South Africans and one Zambian). No mutations
      have been identified in the LRRK2, SNCA, PINK, or DJ-1 genes. Given the unique
      ancestry of SSA populations, their inclusion in genetic studies may provide a
      substantial contribution to the identification of novel genetic factors and
      genetic-environmental interactions underlying this disorder. More initiatives are
      needed to drive further research on PD in these populations and to facilitate
      collaborative projects across Africa. 

PMID- 24079844
TI  - Impact of non-motor symptoms on the quality of life of patients with Parkinson's
      disease: some questions beyond research findings.

PMID- 24079847
TI  - Addressing the negative effect of cross-examination questioning on children's
      accuracy: can we intervene?
AB  - This study investigated whether preinterview interventions could help to
      facilitate children's accuracy under cross-examination-style questioning. Five-
      and 6-year-olds (n = 77; mean [SD] age = 5.84 [0.48] years; 57% boys) and 9- and
      10-year-olds (n = 87; mean [SD] age = 10.30 [0.54] years; 56% boys) took part in
      a staged event and were then interviewed with analogues of direct examination and
      cross-examination. In a pilot study, we ascertained that a brief verbal warning
      about the nature of cross-examination-given immediately prior to the cross
      examination interview-did not influence children's cross-examination accuracy,
      regardless of whether it was delivered by an unfamiliar interviewer or the cross
      examining interviewer. In the main experiment, some children participated in a
      brief intervention involving practice and feedback with cross-examination
      questions. Relative to control children, those who underwent this preparation
      intervention made fewer changes to their direct-examination responses under cross
      examination, changed a smaller proportion of their correct responses, and
      obtained higher ultimate accuracy levels. These findings provide some support for
      the notion that pretrial interventions, if sufficiently comprehensive, could help
      children to maintain accuracy during cross-examination.

PMID- 24079845
TI  - Intronic non-CG DNA hydroxymethylation and alternative mRNA splicing in honey
      bees.
AB  - BACKGROUND: Previous whole-genome shotgun bisulfite sequencing experiments showed
      that DNA cytosine methylation in the honey bee (Apis mellifera) is almost
      exclusively at CG dinucleotides in exons. However, the most commonly used method,
      bisulfite sequencing, cannot distinguish 5-methylcytosine from 5
      hydroxymethylcytosine, an oxidized form of 5-methylcytosine that is catalyzed by
      the TET family of dioxygenases. Furthermore, some analysis software programs
      under-represent non-CG DNA methylation and hydryoxymethylation for a variety of
      reasons. Therefore, we used an unbiased analysis of bisulfite sequencing data
      combined with molecular and bioinformatics approaches to distinguish 5
      methylcytosine from 5-hydroxymethylcytosine. By doing this, we have performed the
      first whole genome analyses of DNA modifications at non-CG sites in honey bees
      and correlated the effects of these DNA modifications on gene expression and
      alternative mRNA splicing. RESULTS: We confirmed, using unbiased analyses of
      whole-genome shotgun bisulfite sequencing (BS-seq) data, with both new data and
      published data, the previous finding that CG DNA methylation is enriched in exons
      in honey bees. However, we also found evidence that cytosine methylation and
      hydroxymethylation at non-CG sites is enriched in introns. Using antibodies
      against 5-hydroxmethylcytosine, we confirmed that DNA hydroxymethylation at non
      CG sites is enriched in introns. Additionally, using a new technique, Pvu-seq
      (which employs the enzyme PvuRts1l to digest DNA at 5-hydroxymethylcytosine sites
      followed by next-generation DNA sequencing), we further confirmed that
      hydroxymethylation is enriched in introns at non-CG sites. CONCLUSIONS: Cytosine
      hydroxymethylation at non-CG sites might have more functional significance than
      previously appreciated, and in honey bees these modifications might be related to
      the regulation of alternative mRNA splicing by defining the locations of the
      introns.

PMID- 24079846
TI  - Withaferin A, a steroidal lactone from Withania somnifera, induces mitotic
      catastrophe and growth arrest in prostate cancer cells.
AB  - Cell cycle deregulation is strongly associated with the pathogenesis of prostate
      cancer. Clinical trials of cell cycle regulators that target either the G0/G1 or
      G2/M phase to inhibit the growth of cancers including prostate cancer are
      increasing. The present study focused on the cell cycle regulatory potential of
      the withanolide withaferin A (1) on prostate cancer cells. Compound 1 induced
      G2/M arrest in both prostate cancer cell lines (PC-3 and DU-145) when treated for
      48 h. The G2/M arrest was accompanied by upregulation of phosphorylated Wee-1,
      phosphorylated histone H3, p21, and Aurora B. On the other hand, downregulation
      of cyclins (A2, B1, and E2) and a reduction in phosphorylated Cdc2 (Tyr15) were
      observed in 1-treated prostate cancer cells. In addition, decreased levels of
      phosphorylated Chk1 (Ser345) and Chk2 (Thr68) were evident in prostate cancer
      cells on treatment with 1. These results suggest that activation of Cdc2 leads to
      arrest in the M phase, with abnormal duplication, and initiation of mitotic
      catastrophe that results in cell death. In conclusion, these results show clearly
      the potential of 1 as a regulator of the G2/M phase of the cell cycle and as a
      therapeutic agent for prostate cancer. 

PMID- 24079848
TI  - Coupled Dirac fermions and neutrino-like oscillations in twisted bilayer
      graphene.
AB  - The low-energy quasiparticles in graphene can be described by a Dirac-Weyl
      Hamiltonian for massless fermions, hence graphene has been proposed to be an
      effective medium to study exotic phenomena originally predicted for relativistic
      particle physics, such as Klein tunneling and Zitterbewegung. In this work, we
      show that another important particle-physics phenomenon, the neutrino
      oscillation, can be studied and observed in a particular graphene system, namely,
      twisted bilayer graphene. It has been found that graphene layers grown
      epitaxially on SiC or by the chemical vapor deposition method on metal substrates
      display a stacking pattern with adjacent layers rotated by an angle with respect
      to each other. The quasiparticle states in two distinct graphene layers act as
      neutrinos with two flavors, and the interlayer interaction between them induces
      an appreciable coupling between these two "flavors" of massless fermions, leading
      to neutrino-like oscillations. In addition, our calculation shows that
      anisotropic transport properties manifest in a specific energy window, which is
      accessible experimentally in twisted bilayer graphene. Combining two graphene
      layers enables us to probe the rich physics involving multiple interacting Dirac
      fermions. 

PMID- 24079849
TI  - Iridium-catalyzed direct arene C-H bond amidation with sulfonyl- and aryl azides.
AB  - Iridium-catalyzed direct ortho C-H amidation of arenes has been shown to work
      well with sulfonyl- and aryl azides as the nitrogen source. The reaction proceeds
      efficiently with a broad range of substrates bearing conventional directing
      groups with excellent functional group compatibility under mild conditions. In
      addition, substrates forming not only 5- but also 6-membered iridacycle
      intermediates undergo the C-H amidation with high selectivity. 

PMID- 24079852
TI  - Impact of brodalumab treatment on psoriasis symptoms and health-related quality
      of life: use of a novel patient-reported outcome measure, the Psoriasis Symptom
      Inventory.
AB  - BACKGROUND: Psoriasis symptoms have a significant negative impact on health
      related quality of life, impairing physical functioning and well-being.
      OBJECTIVE: To evaluate the impact of brodalumab, a human anti-interleukin-17R
      monoclonal antibody, on psoriasis symptom severity as measured by a novel patient
      reported outcome measure, the Psoriasis Symptom Inventory, and dermatology
      specific health-related quality of life as measured by the Dermatology Life
      Quality Index (DLQI). METHODS: This was a secondary analysis of a phase II,
      randomized, double-blind, placebo-controlled clinical study of patients with
      moderate-to-severe psoriasis (n = 198) treated with brodalumab or placebo. This
      analysis assessed Psoriasis Symptom Inventory scores and DLQI scores over time.
      Analyses were conducted on all patients who were randomized and received one or
      more injections of the study drug according to intention to treat using last
      observation carried forward to impute missing data. RESULTS: At week 12, subjects
      in the brodalumab groups had significant improvements in mean Psoriasis Symptom
      Inventory total scores [8.5 (70 mg), 15.8 (140 mg), 16.2 (210 mg) and 12.7 (280
      mg)] compared with placebo (4.8). Mean improvements in DLQI were clinically
      meaningful (>= 5.7) in the brodalumab groups (6.2, 9.1, 9.6 and 7.1,
      respectively) and significantly greater than placebo (3.1). Improvements in
      Psoriasis Symptom Inventory were observed as early as week 2 and in DLQI by week
      4. All eight Psoriasis Symptom Inventory item scores improved significantly among
      the brodalumab groups by week 12. CONCLUSIONS: Results were from a single
      randomized clinical trial and may not generalize to broader patient populations.
      However, treatment with brodalumab provided significant improvement in psoriasis
      symptoms in patients with moderate-to-severe psoriasis.

PMID- 24079853
TI  - Intraduplex DNA-mediated electrochemistry of covalently tethered redox-active
      reporters.
AB  - Intraduplex DNA-mediated reduction is established as a general mechanism for the
      reduction of distally bound stacked redox-active species covalently tethered to
      DNA through flexible alkane linkages. Methylene Blue (MB), Nile Blue (NB), and
      Anthraquinone (AQ) were covalently tethered to DNA with three different covalent
      linkages. Using these reporters DNA electrochemistry was shown to be both DNA
      mediated and intra-, rather than inter-, duplex. Significantly, the charge
      transport pathway occurring through the DNA pi-stack is established by using an
      intervening AC mismatch to break this path. The fact that the DNA-mediated
      reduction of MB occurs primarily via intraduplex intercalation is established
      through varying the proximity and integrity of the neighboring duplex DNA. 

PMID- 24079850
TI  - Transient-state kinetics of apurinic/apyrimidinic (AP) endonuclease 1 acting on
      an authentic AP site and commonly used substrate analogs: the effect of diverse
      metal ions and base mismatches.
AB  - Apurinic/apyrimidinic endonuclease 1 (APE1) is an Mg2+-dependent enzyme
      responsible for incising the DNA backbone 5' to an apurinic/apyrimidinic (AP)
      site. Here, we use rapid quench flow (RQF) techniques to provide a comprehensive
      kinetic analysis of the strand-incision activity (k(chemistry)) of APE1 acting on
      an authentic AP site along with two widely used analogs, a reduced AP site and a
      tetrahydrofuran (THF) site. In the presence of biologically relevant Mg2+, APE1
      incises all three substrates at a rate faster than the resolution of the RQF,
      >=700 s-1. To obtain quantitative values of k(chemistry) and to facilitate a
      comparison of the authentic substrate versus the substrate analogs, we replaced
      Mg2+ with Mn2+ or Ni2+ or introduced a mismatch 5' to the lesion site. Both
      strategies were sufficient to slow k(chemistry) and resulted in rates within the
      resolution of the RQF. In all cases where quantitative rates were obtained,
      k(chemistry) for the reduced AP site is indistinguishable from the authentic AP
      site. Notably, there is a small decrease, ~1.5-fold, in k(chemistry) for the THF
      site relative to the authentic AP site. These results highlight a role in strand
      incision for the C1' oxygen of the AP site and warrant consideration when
      designing experiments using substrate analogs.

PMID- 24079854
TI  - Adherence to oral antineoplastic agents by cancer patients: definition and
      literature review.
AB  - Since the 1990s, oral chemotherapy has been gaining ground as cancer treatment.
      This therapy seems to have few toxic effects and offers patients good quality of
      life. However, in addition to the fears the therapy might generate in patients,
      oral treatment raises a new issue, which, until now, has been marginal in this
      field: therapeutic observance or adherence. We investigated the research into
      adherence to oral chemotherapy among cancer patients published between 1990 and
      July 2013. Studies showed considerable diversity in terms of both the definition
      and measurement of adherence. As well, adherence to antineoplastic therapy is
      affected by the patient's understanding of the treatment and ability to remember
      information provided by the physician, treatment length and psychological
      distress. Our review of the few studies on adherence to anticancer drug treatment
      raises some questions that could be pursued in future research. In light of our
      findings, patients should receive 'therapy education' to help them and their
      support groups better understand the disease and its treatment and to achieve
      optimal health management and improved treatment effectiveness. 

PMID- 24079856
TI  - The immediate response of jejunal mucosa to small bowel heterotopic
      allotransplatation in rats.
AB  - The course of histopathological alterations within jejunal graft architecture
      during the initial adaptation phase in the host body was investigated. Graft
      tissues were compared to the intestinal tissues of the recipients. This study
      demonstrates: (1) renewal of intestinal epithelial lining in the graft biopsies
      during initial hours after transplantation is more likely caused by migration and
      extension of remaining epithelial cells than by their increased mitotic division.
      (2) Distinct decrease in histopathological injury was observed in transplanted
      grafts after 6h, but the morphometrical parameters, particularly villus height
      and wall thickness, remained altered. (3) Significant decrease in apoptotic cell
      death in the epithelial lining within 6h of graft recirculation was accompanied
      by no effect on apoptosis levels of the cells in lamina propria connective
      tissue. (4) Although the apoptosis level in the connective tissue cells was not
      modulated in the grafts within the first hour after transplantation, caspase-3
      dependent apoptosis was decreased significantly. 

PMID- 24079855
TI  - Hallucinations in acutely admitted patients with psychosis, and effectiveness of
      risperidone, olanzapine, quetiapine, and ziprasidone: a pragmatic, randomized
      study.
AB  - BACKGROUND: Hallucinations are prevalent in schizophrenia and related psychotic
      disorders and may have severe consequences for the affected patients.
      Antipsychotic drug trials that specifically address the anti-hallucinatory
      effectiveness of the respective drugs in representative samples are rare. The
      aims of the present study were to investigate the rate and severity of
      hallucinations in acutely admitted psychotic patients at hospital admission and
      discharge or after 6 weeks at the latest, if not discharged earlier (discharge/6
      weeks); and to compare the anti-hallucinatory effectiveness of risperidone,
      olanzapine, quetiapine, and ziprasidone with up to 2 years' follow-up. METHODS:
      Adult patients acutely admitted to an emergency ward for psychosis were
      consecutively randomized to risperidone, olanzapine, quetiapine, or ziprasidone
      and followed for up to 2 years in a pragmatic design. Participants were assessed
      repeatedly using the hallucinatory behavior item of the Positive and Negative
      Syndrome Scale (PANSS). RESULTS: A total of 226 patients, 30.5% of those assessed
      for eligibility, were randomized and 68% were hallucinating at baseline. This
      proportion was reduced to 33% at discharge/6 weeks. In the primary analyses based
      on intention to treat groups of patients experiencing frequent hallucinations,
      the quetiapine and ziprasidone groups both had faster decreases of the mean
      hallucination scores than the risperidone group. CONCLUSIONS: Hallucinations are
      fairly responsive to antipsychotic drug treatment and differential anti
      hallucinatory effectiveness may be found among existing antipsychotic drugs. If
      replicated, this could pave the way for a more targeted pharmacotherapy based on
      individual symptom profiles, rather than on the diagnostic category. TRIAL
      REGISTRATION: ClinicalTrials.gov ID; NCT00932529.

PMID- 24079857
TI  - Are economically "kinder, gentler societies" also greener?
AB  - Several studies examining implications of the modern welfare state arrive at
      rather positive conclusions: generally, they find that economically "kinder,
      gentler societies", that is, countries providing stronger state-sponsored social
      safety nets for their people, perform better on various accounts, such as social
      and political stability, or economic performance. Recent research suggests that
      benign implications also exist for the environment in the sense that investing
      more in social policies may contribute to stronger environmental protection and
      higher environmental quality. We present theoretical arguments in favor, but also
      against this hypothesis, and evaluate it empirically with cross-sectional data
      for 68 countries. In contrast to previous studies, the results offer only weak
      and inconsistent support for the claim that social policies and environmental
      performance are systematically related. This means that governments of
      economically kinder, gentler societies would be ill advised to hope for positive
      "spillover effects" of social policies into the environmental realm. The findings
      also suggest, however, that more disaggregated analyses are necessary, since
      beneficial effects may exist in some environmental domains, but not in others. 

PMID- 24079858
TI  - Methods of international health technology assessment agencies for economic
      evaluations--a comparative analysis.
AB  - BACKGROUND: The number of Health Technology Assessment (HTA) agencies increases.
      One component of HTAs are economic aspects. To incorporate economic aspects
      commonly economic evaluations are performed. A convergence of recommendations for
      methods of health economic evaluations between international HTA agencies would
      facilitate the adaption of results to different settings and avoid unnecessary
      expense. A first step in this direction is a detailed analysis of existing
      similarities and differences in recommendations to identify potential for
      harmonization. The objective is to provide an overview and comparison of the
      methodological recommendations of international HTA agencies for economic
      evaluations. METHODS: The webpages of 127 international HTA agencies were
      searched for guidelines containing recommendations on methods for the preparation
      of economic evaluations. Additionally, the HTA agencies were requested
      information on methods for economic evaluations. Recommendations of the included
      guidelines were extracted in standardized tables according to 13 methodological
      aspects. All process steps were performed independently by two reviewers.
      RESULTS: Finally 25 publications of 14 HTA agencies were included in the
      analysis. Methods for economic evaluations vary widely. The greatest accordance
      could be found for the type of analysis and comparator. Cost-utility-analyses or
      cost-effectiveness-analyses are recommended. The comparator should continuously
      be usual care. Again the greatest differences were shown in the recommendations
      on the measurement/sources of effects, discounting and in the analysis of
      sensitivity. The main difference regarding effects is the focus either on
      efficacy or effectiveness. Recommended discounting rates range from 1.5%-5% for
      effects and 3%-5% for costs whereby it is mostly recommended to use the same rate
      for costs and effects. With respect to the analysis of sensitivity the main
      difference is that oftentimes the probabilistic or deterministic approach is
      recommended exclusively. Methods for modeling are only described vaguely and
      mainly with the rational that the "appropriate model" depends on the decision
      problem. Considering all other aspects a comparison is challenging as
      recommendations vary regarding detailedness and addressed issues. CONCLUSION:
      There is a considerable unexplainable variance in recommendations. Further effort
      is needed to harmonize methods for preparing economic evaluations.

PMID- 24079859
TI  - Time for e-cigarette regulation.

PMID- 24079860
TI  - Hypofractionated breast radiation: preferred standard of care?

PMID- 24079861
TI  - Challenges of accessing cancer medicines in Australia.

PMID- 24079862
TI  - Radiation disasters: an international biobank plan is vital.

PMID- 24079863
TI  - Engaging NGOs in national cancer-control efforts.

PMID- 24079864
TI  - The proton problem.

PMID- 24079865
TI  - Failure of anti-EGFR therapy in p16-positive head and neck cancer.

PMID- 24079866
TI  - p16 post-hoc analyses and Simpson's paradox.

PMID- 24079867
TI  - Failure of anti-EGFR therapy in p16-positive head and neck cancer - authors'
      reply.

PMID- 24079868
TI  - Intercalated chemotherapy and erlotinib: a viable first-line option for patients
      with advanced NSCLC? - authors' reply.

PMID- 24079869
TI  - Intercalated chemotherapy and erlotinib: a viable first-line option for patients
      with advanced NSCLC?

PMID- 24079870
TI  - Air pollution and lung cancer in Europe.

PMID- 24079871
TI  - Air pollution and lung cancer in Europe - authors' reply.

PMID- 24079873
TI  - Present status and future directions of intraoperative radiotherapy.
AB  - In this Review, we summarise recent published work on the use of intraoperative
      radiotherapy to treat common tumour sites in the primary or recurrent setting.
      Techniques, radiobiology, and the physics of intraoperative radiotherapy are also
      explored. Disease sites discussed in this Review include head and neck cancer,
      breast cancer, sarcoma, gastrointestinal cancer, genitourinary cancer,
      gynaecological cancer, thoracic cancer, and palliative applications. 

PMID- 24079872
TI  - Is cancer gene therapy an empty suit?
AB  - Gene therapy as a treatment for cancer is regarded as high in promise, but low in
      delivery, a deficiency that has become more obvious with ever-increasing reports
      of the successful correction of monogenic disorders by this approach. We review
      the commercial and scientific obstacles that have led to these delays and
      describe how they are progressively being overcome. Recent and striking successes
      and correspondingly increased commercial involvement suggest that gene transfer
      could finally become a powerful method for development of safe and effective
      cancer therapeutic drugs. 

PMID- 24079874
TI  - PET imaging of oestrogen receptors in patients with breast cancer.
AB  - Oestrogen receptors are overexpressed in around 70% of all breast cancers, and
      are a target for endocrine therapy. These receptors can be visualised on PET with
      use of 16alpha-[(18)F]-fluoro-17beta-oestradiol ((18)F-FES) as a tracer. Compared
      with biopsy, which enables assessment of individual sites, whole-body (18)F-FES
      PET enables quantification of oestrogen-receptor expression in all metastases. In
      several studies, measurement of tumour protein expression in oestrogen receptors
      by (18)F-FES-PET, concurrent with biopsy, detected oestrogen-receptor-positive
      tumour lesions with a sensitivity of 84% and specificity of 98%. Roughly 45% of
      patients with metastatic breast cancer have discordant oestrogen-receptor
      expression across lesions (ie, (18)F-FES-positive and (18)F-FES-negative
      metastases). Low tumour (18)F-FES uptake in metastases can predict failure of
      hormonal therapy in patients with oestrogen-receptor-positive primary tumours.
      Finally, (18)F-FES-PET has shown that oestrogen-receptor binding capacity changes
      after intervention with hormonal drugs, but findings need to be confirmed.
      Factors other than oestrogen-receptor expression, including menopausal status and
      concomitant therapies, that can affect tumour (18)F-FES uptake must be taken into
      account. 

PMID- 24079875
TI  - Improvement of surgical results for pancreatic cancer.
AB  - Surgery is the only potential hope of cure for patients with pancreatic cancer.
      Advantageous tumour characteristics and complete tumour resection are the factors
      most relevant for a positive prognosis, so detection of premalignant or early
      invasive lesions, combined with safe and oncologically adequate surgery, is an
      important goal. The experience and volume of both the individual surgeon and
      hospital are of paramount importance to achieve low morbidity and adequate
      management of complications. Most pancreatic cancers are locally advanced or
      metastatic when diagnosed and need multimodal therapy. With increasing evidence
      on surgical and perioperative aspects of pancreatic cancer therapy, short-term
      and long-term outcomes of resectable and borderline resectable pancreatic cancer
      are improving. 

PMID- 24079877
TI  - Very severe chronic ventricular tachycardia due to an aneurysm in the left main
      coronary artery and a giant aneurysm-related pseudoaneurysm.

PMID- 24079876
TI  - Unilateral lung transplantation using right and left upper lobes: an experimental
      study.
AB  - OBJECTIVE: The shortage of organ donors is a serious problem in Japan. The right
      and left upper lobes of rejected extended-criteria lungs have the potential to be
      used for downsized lung transplantation; however, the 2 upper lobes are too small
      for a size-matched recipient. The present study investigated the feasibility of
      unilateral transplantation using the right and left upper lobes. METHODS: After
      harvesting the heart-lung block from donor swine, a left lung graft was created
      using the right and left upper lobes and transplanted into the left thoracic
      space of the recipient swine (group A, n = 5). We then evaluated graft function
      for 6 hours and compared these results with those of a control group (group B, n
      = 5), in which orthotopic left lung transplantation had been performed. RESULTS:
      The mean partial pressure of oxygen in the arterial blood gas after reperfusion
      was 507 mm Hg in group A and 463 mm Hg in group B (P = .2). The mean pulmonary
      arterial pressure was 30.3 mm Hg in group A and 27.5 mm Hg in group B (P = .4).
      The mean airway pressure was 6.4 mm Hg in group A and 6.2 mm Hg in group B (P =
      .7). CONCLUSIONS: Our results suggest that unilateral left lung transplantation
      using the right and left upper lobes is technically and functionally feasible for
      size-matched recipients. In addition, this technique enables the use of rejected
      lungs if the upper lobes are still intact.

PMID- 24079878
TI  - Mechanical versus bioprosthetic mitral valve replacement in patients <65 years
      old.
AB  - OBJECTIVE: Because of its durability, the mechanical valve is typically chosen
      for young patients undergoing mitral valve replacement (MVR). However, a
      bioprosthetic valve might have the benefit of valve-in-valve transcatheter valve
      replacement when valve failure occurs. We examined the outcomes in patients who
      had undergone mechanical valve MVR (MVRm) versus bioprosthetic valve MVR (MVRb)
      in patients aged <65 years. METHODS: A total of 768 consecutive patients aged <65
      years, who had undergone MVR from January 1991 to June 2012 were identified.
      Propensity matching was used to derive a case-control subset for analysis. Long
      term outcomes were collected by chart review, routine patient follow-up, and
      query of the Social Security Death Index. The postoperative and long-term
      outcomes of interest included combined stroke and embolic events, reoperations,
      and mortality. RESULTS: Of 768 consecutive patients, 627 were in the MVRm and 141
      in the MVRb group. Propensity score matching yielded a cohort of 125 MVRb (89%)
      and 125 control MVRm patients with similar etiology mixes. The groups were
      similar in age (MVRm, 53.2 +/- 9.0 years; MVRb, 53.8 +/- 10.6 years; P = .617)
      and other preoperative characteristics. The postoperative outcomes were also
      similar between the 2 groups, including reoperation for bleeding, stroke, deep
      sternal infection, sepsis, and length of hospital stay. The operative mortality
      was also similar (MVRm, 5.6%; MVRb, 8.0%; P = .617). However, Kaplan-Meier
      analysis showed the MVRb group had a greater reoperation rate (P = .001) and
      shorter estimated survival (11.3 vs 13.5 years, P = .004). The incidence of
      bleeding and stroke or embolic events between the 2 groups was similar.
      CONCLUSIONS: In the present report, MVRb for patients <65 years old was
      associated with a high reoperation rate and decreased survival. Although a future
      transcatheter valve-in-valve technique for a failed bioprosthetic valve might
      reduce the risk of reoperation, this finding confirms the safety of mechanical
      valves in this group.

PMID- 24079879
TI  - Surgical strategies for anomalous origin of coronary artery from pulmonary artery
      in adults.
AB  - OBJECTIVES: Limited data are available regarding the surgical strategies for an
      anomalous origin of the coronary artery from the pulmonary artery (ACAPA) in
      adulthood. We reviewed our surgical experience with ACAPA in adults. METHODS:
      From January 1960 to July 2011, 10 adults (30% men), aged 18 to 78 years (median,
      43), underwent surgical repair of ACAPA. Anomalous left (ALCAPA) was present in
      7, anomalous right (ARCAPA) in 2, and anomalous left anterior descending artery
      in 1. Most (90%) were symptomatic, with 7 (70%) having ischemic changes on a
      preoperative at rest or stress electrocardiogram. One patient had undergone
      previous ligation of ALCAPA in childhood. The mean left ventricular ejection
      fraction was 56% +/- 10%, with mild dysfunction in 4. RESULTS: Of the 10
      patients, 7 underwent repair by coronary artery button transfer to the aorta,
      with 2 requiring an interposition saphenous vein graft. In 3 patients, coronary
      transfer was not possible, and coronary artery bypass grafting with closure of
      the ACAPA was performed. The mean follow-up was 8.6 years (maximum, 37). Two late
      deaths occurred from noncardiac causes. One patient with ALCAPA who underwent
      direct reimplantation subsequently required coronary artery bypass grafting for
      left main stenosis, likely secondary to tension. At the last follow-up visit, all
      patients were in New York Heart Association class I or II. The postoperative left
      ventricular ejection fraction was similar at 53% +/- 9%; No significant
      improvement was seen in those with below normal ejection fraction. CONCLUSIONS:
      Establishment of a dual coronary artery system with coronary transfer is
      preferred, even if an interposition graft is required. Coronary artery bypass
      grafting with closure of ACAPA should be reserved for when coronary transfer is
      not feasible. Surgical correction of ACAPA should be considered before the onset
      of left ventricular dysfunction.

PMID- 24079880
TI  - Preoperative B-type natriuretic peptide levels are associated with outcome after
      total cavopulmonary connection (Fontan).
AB  - OBJECTIVE: The study objective was to determine the association between
      preoperative B-type natriuretic peptide levels and outcome after total
      cavopulmonary connection. Surgical palliation of univentricular cardiac defects
      requires a series of staged operations, ending in a total cavopulmonary
      connection. Although outcomes have improved, there remains an unpredictable risk
      of early total cavopulmonary connection takedown. The prediction of adverse
      postoperative outcomes is imprecise, despite an extensive preoperative
      evaluation. METHODS: We prospectively enrolled 50 patients undergoing total
      cavopulmonary connection. We collected preoperative clinical data, preoperative
      plasma B-type natriuretic peptide levels, and postoperative outcomes, including
      the incidence of an adverse outcome within 1 year of surgery (defined as death,
      total cavopulmonary connection takedown, or the need for cardiac
      transplantation). RESULTS: The mean age of patients was 4.7 years (standard
      deviation, 2.1 years). The median (interquartile range) preoperative B-type
      natriuretic peptide levels were higher in patients who required total
      cavopulmonary connection takedown and early postoperative mechanical cardiac
      support (n = 3; median, 55; interquartile range, 42-121) compared with those with
      a good outcome (n = 47; median, 11; interquartile range, 5-17) (P < .05). A
      preoperative B-type natriuretic peptide level of 40 pg/mL or greater was highly
      associated with the need for total cavopulmonary connection takedown
      (sensitivity, 100%; specificity, 93%; P < .05), yielding a positive predictive
      value of 50% and a negative predictive value of 100%. Higher preoperative B-type
      natriuretic peptide levels also were associated with longer intensive care unit
      length of stay, longer hospital length of stay, and increased incidence of low
      cardiac output syndrome (P < .05). CONCLUSIONS: Preoperative B-type natriuretic
      peptide blood levels are uniquely associated with the need for mechanical support
      early after total cavopulmonary connection and total cavopulmonary connection
      takedown, and thus may provide important information in addition to the standard
      preoperative assessment.

PMID- 24079881
TI  - Histological characteristics of gastric mucosa prior to Helicobacter pylori
      eradication may predict gastric cancer.
AB  - OBJECTIVE: Although Helicobacter pylori (H. pylori) eradication has been shown to
      inhibit gastric cancer, it does not completely suppress it. Therefore, risk
      factors of gastric cancer development following H. pylori eradication were
      examined. MATERIAL AND METHODS: A total of 2355 patients (1501 males and 824
      females) underwent successful eradication of H. pylori. Endoscopic atrophy,
      histological gastritis, atrophy, intestinal metaplasia (IM), and operative link
      for gastritis assessment (OLGA) staging were subsequently evaluated. RESULTS:
      Following eradication, 33/2355 patients (25 males and 8 females) developed
      gastric cancer. Compared to a nongastric cancer group that was matched according
      to gender and age, the incidence of endoscopic atrophy (3.52 +/- 1.45 vs. 4.85 +/
      1.18, p < 0.001), histological atrophy at the greater curvature of the antrum
      (1.42 +/- 0.80 vs. 1.95 +/- 0.86, p = 0.0059), inflammation (2.05 +/- 0.59 vs.
      2.33 +/- 0.66, p = 0.031), IM at the greater curvature of the corpus (0.06 +/-
      0.30 vs. 0.24 +/- 0.54, p = 0.029), the ratio of OLGA-stage 0-II/III, IV (13/8
      vs. 55/11, p = 0.038) were significantly higher for the gastric cancer group.
      Multivariate analysis also showed the highest odds ratio (6.26, 95% confidence
      interval or CI, 1.28-30.60, p = 0.023) for IM at the greater curvature of the
      corpus. CONCLUSIONS: Severe endoscopical atrophy, OLGA staging, histological
      atrophy at the antrum, inflammation, and particularly IM at the corpus, were
      identified as risk factors for gastric cancer development following H. pylori
      eradication. Therefore, eradication should be performed before these predictors
      develop.

PMID- 24079882
TI  - Phomapyrrolidones A-C, antitubercular alkaloids from the endophytic fungus Phoma
      sp. NRRL 46751.
AB  - Three new alkaloids, phomapyrrolidones A-C (1-3), bearing a cyclopenta[b]fluorene
      ring system were isolated from the mycelium extract of the endophytic fungal
      strain Phoma sp. NRRL 46751, inhabiting Saurauia scaberrinae. Methylation of 1
      afforded its N-methyl derivative 4. The planar structures and relative
      configurations of 1-4 were elucidated by extensive spectroscopic analysis.
      Phomapyrrolidones B (2) and C (3) exhibited weak antitubercular activity at
      subcytotoxic concentrations. 

PMID- 24079883
TI  - Super-adhesive polymer-silica nanocomposite layers.
AB  - Atomized spray plasma deposition (ASPD) using a precursor mixture of 2
      hydroxyethyl methacrylate and methacryloyl-functionalized 15 nm silica
      nanoparticles leads to the formation of poly(2-hydroxyethyl methacrylate)-silica
      nanocomposite layers. The direct application of these coatings to overlapping
      glass-glass joints gives rise to excellent in situ adhesion reaching 84 MPa shear
      bond strength and 6 GPa shear modulus prior to the onset of adherent (bulk glass)
      failure. This significant enhancement in interfacial adhesion arises due to the
      silica nanoparticle surface methacryloyl groups enhancing cross-linking
      throughout the nanocomposite layer. 

PMID- 24079884
TI  - Evaluation of the adverse event profile and pharmacodynamics of toceranib
      phosphate administered to dogs with solid tumors at doses below the maximum
      tolerated dose.
AB  - BACKGROUND: The receptor kinase inhibitor toceranib phosphate (Palladia) was
      approved for use in dogs in 2009 using a dose of 3.25 mg/kg administered every
      other day. Preliminary data suggests that lower doses of toeceranib may be
      associated with a reduced adverse event profile while maintaining sufficient drug
      exposure to provide biologic activity. The purpose of this study was to determine
      the Cmax of toceranib in dogs with solid tumors receiving 2.5-2.75 mg/kg every
      other day and to document the adverse events associated with this dose rate.
      Secondary objectives included determination of plasma VEGF concentrations in
      treated dogs and response to therapy. RESULTS: Dogs with solid tumors were
      administered toceranib at an intended target dose ranging from 2.5-2.75 mg/kg
      every other day and plasma samples were obtained for analysis of toceranib and
      VEGF plasma concentrations on days 0, 7, 14 and 30 of the study at 6 and 8 hours
      post drug administration. Additionally, plasma samples were obtained at 0, 1, 2,
      6, 8, and 12 hours from dogs on day 30 for confirmation of Cmax. Response to
      therapy was assessed using standard RECIST criteria and adverse events were
      characterized using the VCOG-CTCAE. Toceranib administered at doses between 2.4
      2.9 mg/kg every other day resulted in an average 6-8 hr plasma concentration
      ranging from 100-120 ng/ml, well above the 40 ng/ml concentration associated with
      target inhibition. Plasma VEGF concentrations increased significantly over the 30
      day treatment period indicating that VEGFR2 inhibition was likely achieved in the
      majority of dogs. The lower doses of toceranib used in this study were associated
      with a substantially reduced adverse event profile compared to the established
      label dose of 3.25 mg/kg EOD. CONCLUSIONS: Doses of toceranib ranging from 2.4
      2.9 mg/kg every other day provide drug exposure considered sufficient for target
      inhibition while resulting in an adverse event profile substantially reduced from
      that associated with the label dose of toceranib. This lower dose range of
      toceranib should be considered for future use in dogs with cancer.

PMID- 24079886
TI  - Restricted access: on the nature of adsorption/desorption hysteresis in
      amorphous, microporous polymeric materials.
AB  - The phenomenon of low-pressure adsorption/desorption hysteresis, which is
      commonly observed in microporous polymers, is investigated by detailed gas
      adsorption studies. Diffusional limitations by pore blocking effects, which arise
      as a consequence of the micropore morphology and connectivity, are discussed as
      the origin of the hysteresis rather than swelling effects, which have been
      suggested previously. Micropores with narrow openings, which cannot be filled
      easily, are expected to be present next to open pores. Those pores are termed
      restricted-access pores and are only filled in the course of the adsorption
      process as a consequence of the increasing solvation pressure exhibited from
      already filled micropores. As a consequence of the results presented here, it is
      suggested to use the desorption branch in addition to the adsorption branch for
      the extraction of the porosity characteristics, such as specific surface area,
      pore volume, and pore size distribution. The magnitude of the low-pressure
      hysteresis might hence give an idea of the micropore connectivity, which is
      important information for potential applications. 

PMID- 24079885
TI  - RNA-Seq of Bacillus licheniformis: active regulatory RNA features expressed
      within a productive fermentation.
AB  - BACKGROUND: The production of enzymes by an industrial strain requires a complex
      adaption of the bacterial metabolism to the conditions within the fermenter.
      Regulatory events within the process result in a dynamic change of the
      transcriptional activity of the genome. This complex network of genes is
      orchestrated by proteins as well as regulatory RNA elements. Here we present an
      RNA-Seq based study considering selected phases of an industry-oriented
      fermentation of Bacillus licheniformis. RESULTS: A detailed analysis of 20 strand
      specific RNA-Seq datasets revealed a multitude of transcriptionally active
      genomic regions. 3314 RNA features encoded by such active loci have been
      identified and sorted into ten functional classes. The identified sequences
      include the expected RNA features like housekeeping sRNAs, metabolic riboswitches
      and RNA switches well known from studies on Bacillus subtilis as well as a
      multitude of completely new candidates for regulatory RNAs. An unexpectedly high
      number of 855 RNA features are encoded antisense to annotated protein and RNA
      genes, in addition to 461 independently transcribed small RNAs. These antisense
      transcripts contain molecules with a remarkable size range variation from 38 to
      6348 base pairs in length. The genome of the type strain B. licheniformis DSM13
      was completely reannotated using data obtained from RNA-Seq analyses and from
      public databases. CONCLUSION: The hereby generated data-sets represent a solid
      amount of knowledge on the dynamic transcriptional activities during the
      investigated fermentation stages. The identified regulatory elements enable
      research on the understanding and the optimization of crucial metabolic
      activities during a productive fermentation of Bacillus licheniformis strains.

PMID- 24079888
TI  - Reply to letter to the editor: Orofacial granulomatosis--a diagnostic enigma.

PMID- 24079887
TI  - Mechanistic basis for the potent anti-angiogenic activity of semaphorin 3F.
AB  - Neuropilin-1 (Nrp1), an essential type I transmembrane receptor, binds two
      secreted ligand families, vascular endothelial growth factor (VEGF) and class III
      Semaphorin (Sema3). VEGF-A and Sema3F have opposing roles in regulating Nrp1
      vascular function in angiogenesis. VEGF-A functions as one of the most potent pro
      angiogenic cytokines, while Sema3F is a uniquely potent endogenous angiogenesis
      inhibitor. Sema3 family members require proteolytic processing by furin to allow
      competitive binding to Nrp1. We demonstrate that the furin-processed C-terminal
      domain of Sema3F (C-furSema) potently inhibits VEGF-A-dependent activation of
      endothelial cells. We find that this potent activity is due to unique
      heterobivalent engagement of Nrp1 by two distinct sites in the C-terminal domain
      of Sema3F. One of the sites is the C-terminal arginine, liberated by furin
      cleavage, and the other is a novel upstream helical motif centered on the
      intermolecular disulfide. Using a novel chimeric C-furSema, we demonstrate that
      combining a single C-terminal arginine with the helical motif is necessary and
      sufficient for potent inhibition of binding of VEGF-A to Nrp1. We further
      demonstrate that the multiple furin-processed variants of Sema3A, with the
      altered proximity of the two binding motifs, have dramatically different
      potencies. This suggests that furin processing not only switches Sema3 to an
      activated form but also, depending on the site processed, can also tune potency.
      These data establish the basis for potent competitive binding of Sema3 to Nrp1
      and provide a basis for the design of bivalent Nrp inhibitors. 

PMID- 24079889
TI  - Orofacial granulomatosis--a diagnostic enigma.

PMID- 24079890
TI  - A biodegradable microvessel scaffold as a framework to enable vascular support of
      engineered tissues.
AB  - A biodegradable microvessel scaffold comprised of distinct parenchymal and
      vascular compartments separated by a permeable membrane interface was
      conceptualized, fabricated, cellularized, and implanted. The device was designed
      with perfusable microfluidic channels on the order of 100 MUm to mimic small
      blood vessels, and high interfacial area to an adjacent parenchymal space to
      enable transport between the compartments. Poly(glycerol sebacate) (PGS)
      elastomer was used to construct the microvessel framework, and various assembly
      methods were evaluated to ensure robust mechanical integrity. In vitro studies
      demonstrated the differentiation of human skeletal muscle cells cultured in the
      parenchymal space, a 90% reduction in muscle cell viability due to trans-membrane
      transport of a myotoxic drug from the perfusate, and microvessel seeding with
      human endothelial cells. In vivo studies of scaffolds implanted subcutaneously
      and intraperitoneally, without or with exogenous cells, into nude rats
      demonstrated biodegradation of the membrane interface and host blood cell
      infiltration of the microvessels. This modular, implantable scaffold could serve
      as a basis for building tissue constructs of increasing scale and clinical
      relevance.

PMID- 24079891
TI  - Integration of a calcined bovine bone and BMSC-sheet 3D scaffold and the
      promotion of bone regeneration in large defects.
AB  - Reconstruction of large area bone defect with mechanical integrity to the
      skeleton is important for patient's rehabilitation. However with the limitation
      of scaffold material and suitable seed cell sources, the best treating strategy
      remains to be identified though various tissue engineering methods were reported.
      In this study, we investigated the feasibility of applying calcined bovine bone
      (CBB) which was coated by allograft bone marrow mesenchymal stem cells (BMSC)
      sheet as a 3D scaffold material in bone repairing tissue engineering. The new
      scaffold material was implanted into osteoporosis rat cranial bone defects and
      repairing critical size bone defects (8 mm diameter). Data showed that CBB-BMSC
      sheet combination had a stronger potential in osteogenic differentiation and
      mineralized formation both in vitro and in vivo than CBB-BMSC combination. In in
      vitro study BMSC-sheet had a more feasible characteristic upon bone repairing
      including richer ECM, larger mineralized area and stronger ALP activity in
      addition with a significant higher mRNA expression of osteogenic maker such as
      BMP-2, b-FGF, Col 1a1, OSX and Runx-2 than the control group. In in vivo study 3D
      reconstruction of micro CT, HE staining and bone strength results showed that
      newly formed bone in CBB-BMSC-sheet group was significant higher than that in CBB
      BMSC group at 4, 8 and 12 weeks after transplantation in the aspect of area and
      volume. What was more, results indicated that allograft BMSC-sheet had survivaled
      in the scaffold material and participated in the newly formed bone which had the
      same thickness with surrounding autologous bone tissues after transplantation.
      Results of our study demonstrated that CBB-BMSC-sheet combination was a promising
      strategy in healing of large area bone defect in osteoporosis.

PMID- 24079892
TI  - Dual delivery of PDGF and simvastatin to accelerate periodontal regeneration in
      vivo.
AB  - The emphasis on periodontal regeneration has been shifted towards the
      harmonization of bioactive molecules and physiological phases during
      regeneration. This study investigated whether the combination and sequential
      release of platelet-derived growth factor (PDGF, mitogen) and simvastatin
      (differentiation factor) facilitated periodontal regeneration. PDGF and
      simvastatin were encapsulated in double-walled poly-( d,l-lactide) and poly-(d,l
      lactide-co-glycolide) (PDLLA-PLGA) microspheres using the co-axial
      electrohydrodynamic atomization technique. Critical-sized periodontal defects on
      rat maxillae were filled with microspheres encapsulating BSA-in-core-shell (BB),
      PDGF-in-shell (XP), simvastatin-in-core and BSA-in-shell (SB), simvastatin-in
      core and PDGF-in-shell, or unfilled with microspheres (XX), and examined at 14
      and 28 days post-operatively. The resultant microspheres were around 15 MUm
      diameter with distinct core-shell structure, and the fast-release of PDGF
      followed by slow-release of simvastatin was noted in the SP group. The SP group
      demonstrated significantly greater bone volume fraction and decreased trabecular
      separation compared to the XX group at day 14, and milder inflammatory cells
      infiltration and elevated tartrate-resistant acid phosphatase level were noted at
      day 28. Fibers were also well-aligned and obliquely inserted onto the root
      surface similar to native periodontal ligament with signs of cementogenesis in
      the SP group. In conclusion, the combination and sequential-release of PDGF
      simvastatin accelerates the regeneration of the periodontal apparatus.

PMID- 24079893
TI  - G-diversity discovered.

PMID- 24079894
TI  - The ongoing quest for universal patterns of plant function.

PMID- 24079895
TI  - Marker-free phenotyping of tumor cells by fractal analysis of reflection
      interference contrast microscopy images.
AB  - Phenotyping of tumor cells by marker-free quantification is important for cancer
      diagnostics. For the first time, fractal analysis of reflection interference
      contrast microscopy images of single living cells was employed as a new method to
      distinguish between different nanoscopic membrane features of tumor cells. Since
      tumor progression correlates with a higher degree of chaos within the cell, it
      can be quantified mathematically by fractality. Our results show a high accuracy
      in identifying malignant cells with a failure chance of 3%, which is far better
      than today's applied methods. 

PMID- 24079896
TI  - Antioxidant properties of cerium oxide nanocrystals as a function of nanocrystal
      diameter and surface coating.
AB  - This work examines the effect of nanocrystal diameter and surface coating on the
      reactivity of cerium oxide nanocrystals with H2O2 both in chemical solutions and
      in cells. Monodisperse nanocrystals were formed in organic solvents from the
      decomposition of cerium precursors, and subsequently phase transferred into water
      using amphiphiles as nanoparticle coatings. Quantitative analysis of the
      antioxidant capacity of CeO2-x using gas chromatography and a luminol test
      revealed that 2 mol of H2O2 reacted with every mole of cerium(III), suggesting
      that the reaction proceeds via a Fenton-type mechanism. Smaller diameter
      nanocrystals containing more cerium(III) were found to be more reactive toward
      H2O2. Additionally, the presence of a surface coating did not preclude the
      reaction between the nanocrystal surface cerium(III) and hydrogen peroxide. Taken
      together, the most reactive nanoparticles were the smallest (e.g., 3.8 nm
      diameter) with the thinnest surface coating (e.g., oleic acid). Moreover, a
      benchmark test of their antioxidant capacity revealed these materials were 9
      times more reactive than commercial antioxidants such as Trolox. A unique feature
      of these antioxidant nanocrystals is that they can be applied multiple times:
      over weeks, cerium(IV) rich particles slowly return to their starting cerium(III)
      content. In nearly all cases, the particles remain colloidally stable (e.g.,
      nonaggregated) and could be applied multiple times as antioxidants. These
      chemical properties were also observed in cell culture, where the materials were
      able to reduce oxidative stress in human dermal fibroblasts exposed to H2O2 with
      efficiency comparable to their solution phase reactivity. These data suggest that
      organic coatings on cerium oxide nanocrystals do not limit the antioxidant
      behavior of the nanocrystals, and that their redox cycling behavior can be
      preserved even when stabilized. 

PMID- 24079897
TI  - Joint task force recommendations for credentialing of bariatric surgeons.

PMID- 24079898
TI  - Blueprint for the future of metabolic and bariatric surgery.

PMID- 24079899
TI  - Laparoendoscopic single-site surgery for the placement of an adjustable gastric
      band: a large cohort comparison.
AB  - BACKGROUND: Laparoendoscopic single-site (LESS) surgery has been shown to be a
      well-tolerated alternative for the placement of an adjustable gastric band. To
      date, only small series have suggested that this approach may provide potential
      clinical benefits over standard multiport laparoscopy. The objective of this
      study was to compare the outcomes of patients undergoing LESS adjustable gastric
      banding (LESS-AGB) and a cohort of patients undergoing standard multiport
      laparoscopic adjustable gastric banding (LAGB). METHODS: A total of 206 patients
      underwent placement of an adjustable gastric band. Of these, 106 patients
      underwent LESS-AGB and were compared with a demographically similar cohort of 100
      patients who underwent standard LAGB. Data collected included operative time,
      parenteral and oral narcotic consumption, duration of patient controlled
      analgesia (PCA) device, subjective pain scores using the 0-10 numeric pain
      intensity scale, and length of stay. Unpaired t test was used for analysis.
      RESULTS: Compared with multiport LAGB patients, LESS-AGB patients reported
      significantly less pain at the first postoperative hour (P = .012), twelfth
      postoperative hour (P = .017), and twenty-fourth postoperative hour (P = .012),
      and consumed fewer oral analgesic tablets (P = .012). Operative times were
      significantly longer in the LESS-AGB group (P = .029). No significant differences
      were seen in duration of PCA, parenteral narcotic consumption, or length of stay.
      One LESS-AGB case required conversion to multiport laparoscopy. Complication
      rates were similar between the 2 groups. CONCLUSION: LESS-AGB is associated with
      less pain and less oral analgesic consumption than multiport LAGB. Given these
      clinical advantages and superior cosmetic results, laparoendoscopic single-site
      surgery may be an attractive alternative approach for patients considering LAGB.

PMID- 24079900
TI  - Comment on: Laparoendoscopic single-site surgery for the placement of an
      adjustable gastric band: a large cohort comparison.

PMID- 24079901
TI  - Mean fourteen-year, 100% follow-up of laparoscopic adjustable gastric banding for
      morbid obesity.
AB  - BACKGROUND: Many studies of short-term to mid-term outcomes after laparoscopic
      adjustable gastric banding (LAGB) have been published, but reliable long-term
      outcome reports with a minimum follow up >= 10 years in a sufficient number of
      included patients are still scarce. The objective of this study was to evaluate
      the long-term results after LAGB. METHODS: Sixty consecutive patients (44 women,
      16 men) were treated for morbid obesity by LAGB between 1996 and 1999. Median age
      of the patients at the time of operation was 45 years (range 21-64). Median
      preoperative body mass index (BMI, kg/m(2)) was 45 (range 35-55). All patients
      were asked to adhere to a strict follow-up program. Patients' BMI and percentage
      excess weight loss (%EWL) were calculated in the hospital's database for
      bariatric patients, and excess weight was taken as the weight in kilograms above
      the weight at BMI of 25 kg/m(2). RESULTS: Complete data on all 60 patients could
      be assessed; thus, the overall rate of follow-up was 100%. After a median (range)
      follow-up of 14.1 years (13.2-16.8 years), the mean BMI (SD) dropped from 45 (5)
      to 36 (6) kg/m(2), with a mean (SD) EWL of 49% (29). At 15 years of follow-up, 29
      (48%) bands have been removed, and 38 (63%) reoperations have been performed in
      29 (48%) patients. Almost 70% received further treatment for their morbid obesity
      after band removal. Of those patients with the band still in place at 14 years,
      40% had more than 50% EWL and 20% had less than 25% EWL. There was no mortality
      related to the primary or revisional operations, but 2 patients died of unrelated
      causes. CONCLUSIONS: Mean %EWL after LAGB after more than 14 years was fairly
      good-49%. However, a reoperation rate of more than 60% in 48% of the patients and
      a band removal rate of almost 50% may indicate that LAGB cannot be recommended as
      a primary procedure to the general morbidly obese population.

PMID- 24079902
TI  - Comment on: Mean fourteen-year, 100% follow-up of laparoscopic adjustable gastric
      banding for morbid obesity.

PMID- 24079903
TI  - Letter to the editor: Response to JAMA article which did not accept these letters
      delineating numerous problems with the published study.

PMID- 24079905
TI  - A case report of the early results of laparoscopic bariatric surgery in six
      completely nonambulatory patients.

PMID- 24079906
TI  - A standardized method for measuring intercellular spaces in esophageal biopsies
      in patients with suspected gastroesophageal reflux disease (the intercellular
      space ratio).
AB  - OBJECTIVE: Dilated intercellular space (DIS) in esophageal biopsies is regarded
      as a possible early sign of mucosal injury in gastroesophageal reflux disease
      (GERD). This study presents a standardized approach of intercellular space
      measurement. MATERIAL AND METHODS: Distal and proximal esophageal biopsies were
      taken from 19 patients with suspected GERD, and examined with TEM. A grid
      containing 150 line-crossing points was applied upon each photomicrograph. The
      number of points falling on the intercellular space was divided by the total
      number of points of the grid, thereby creating a ratio called the intercellular
      space ratio (ISR). The ISR method was validated with regard to intra- and
      interobserver agreement, and was compared to a widely used method for measuring
      intercellular space diameter developed by Tobey et al. (Tobey NA, Carson JL,
      Alkiek RA, Orlando RC. Dilated intercellular spaces: a morphological feature of
      acid reflux-damaged human esophageal epithelium. Gastroenterology
      1996;111(5):1200-1205). The ISR was also compared to other markers for GERD.
      Results. Pearson's correlation coefficients for intra- and interobserver
      agreement were 0.91 (p < 0.001) and 0.82 (p < 0.001), respectively. The Pearson's
      correlation coefficient between the ISR and the intercellular space diameter
      according to Tobey et al., measured in the same micrographs, was 0.32 (p <
      0.001). The proximal ISR correlated significantly with the distal ISR (Spearman's
      rho = 0.57, p = 0.010), and with heartburn symptom score (Spearman's rho = 0.50,
      p = 0.028). CONCLUSIONS: The ISR showed a high intraobserver and interobserver
      agreement. It also displayed good external validity when compared to other
      markers for gastroesophageal reflux. A rather poor correlation was however found
      between the ISR and the intercellular space diameter measured as described by
      Tobey et al.

PMID- 24079907
TI  - Biomolecular adsorption at aqueous silver interfaces: first-principles
      calculations, polarizable force-field simulations, and comparisons with gold.
AB  - The molecular simulation of biomolecules adsorbed at noble metal interfaces can
      assist in the development of bionanotechnology applications. In line with
      advances in polarizable force fields for adsorption at aqueous gold interfaces,
      there is scope for developing a similar force field for silver. One way to
      accomplish this is via the generation of in vacuo adsorption energies calculated
      using first-principles approaches for a wide range of different but biologically
      relevant small molecules, including water. Here, we present such first-principles
      data for a comprehensive range of bio-organic molecules obtained from plane-wave
      density functional theory calculations using the vdW-DF functional. As reported
      previously for the gold force field, GolP-CHARMM (Wright, L. B.; Rodger, P. M.;
      Corni, S.; Walsh, T. R. GolP-CHARMM: first-principles based force-fields for the
      interaction of proteins with Au(111) and Au(100). J. Chem. Theory Comput. 2013,
      9, 1616-1630), we have used these data to construct a a new force field, AgP
      CHARMM, suitable for the simulation of biomolecules at the aqueous Ag(111) and
      Ag(100) interfaces. This force field is derived to be consistent with GolP-CHARMM
      such that adsorption on Ag and Au can be compared on an equal footing. Our force
      fields are used to evaluate the water overlayer stability on both silver and
      gold, finding good agreement with known behaviors. We also calculate and compare
      the structuring (spatial and orientational) of liquid water adsorbed at both
      silver and gold. Finally, we report the adsorption free energy of a range of
      amino acids at both the Au(111) and Ag(111) aqueous interfaces, calculated using
      metadynamics. Stronger adsorption on gold was noted in most cases, with the
      exception being the carboxylate group present in aspartic acid. Our findings also
      indicate differences in the binding free energy profile between silver and gold
      for some amino acids, notably for His and Arg. Our analysis suggests that the
      relatively stronger structuring of the first water layer on silver, relative to
      gold, could give rise to these differences. 

PMID- 24079908
TI  - The effectiveness of a storybook in lessening anxiety in children undergoing
      tonsillectomy and adenoidectomy in Northern Ireland.
AB  - AIM: This study aimed to assess the effectiveness of a storybook, entitled, The
      Tale of Woody's Tonsils, written by Anne Marie Tunney, on reducing the level of
      anxiety of children aged 5-11 years who were undergoing tonsillectomy and
      adenoidectomy in one hospital in Northern Ireland. BACKGROUND/LITERATURE REVIEW:
      Psychological preparation of children for surgery impacts coping. There is
      evidence, in both adult and pediatric studies, that effective psychological
      preparation for a surgical procedure has an impact on the individuals' coping
      ability with reduced levels of anxiety leading to better post-operative outcome,
      faster recovery and a reduction in long term sequelae associated with admission
      to hospital. A storybook, as a method of preparation, has been recommended by a
      number of researchers but the effectiveness of this in reducing anxiety has not
      yet been investigated in the UK. Previous studies have mainly used only one
      research instrument for anxiety measurement and child self-report is not a
      commonly used feature of such research. DESIGN AND METHODOLOGY: A quasi
      experimental study involving 80 children was conducted using a repeated measures
      design. Children attending a pre-assessment clinic were randomly allocated to
      either an experimental group (received the storybook) or a control group (did not
      get the storybook). Anxiety was tested both pre- and post-intervention using a
      self-report Hospital Fears Rating Scale and Child Drawing: Hospital, a projective
      technique based on children's drawings. FINDINGS: The storybook was found to be
      effective in reducing pre-operative anxiety and was found to be particularly
      effective for females and in the 7-year-old age group. Practice Implications;
      This study demonstrates the storybook's effectiveness for alleviating anxiety and
      advocates the use of child focused anxiety measurement tools. It reinforces the
      need for pre assessment to include exploration of anxiety triggers so that
      preoperative preparation and nursing care can be individualized for each child.

PMID- 24079909
TI  - The impact of different ale brewer's yeast strains on the proteome of immature
      beer.
AB  - BACKGROUND: It is well known that brewer's yeast affects the taste and aroma of
      beer. However, the influence of brewer's yeast on the protein composition of beer
      is currently unknown. In this study, changes of the proteome of immature beer,
      i.e. beer that has not been matured after fermentation, by ale brewer's yeast
      strains with different abilities to degrade fermentable sugars were investigated.
      RESULTS: Beers were fermented from standard hopped wort (13 degrees  Plato) using
      two ale brewer's yeast (Saccharomyces cerevisiae) strains with different
      attenuation degrees. Both immature beers had the same alcohol and protein
      concentrations. Immature beer and unfermented wort proteins were analysed by 2-DE
      and compared in order to determine protein changes arising from fermentation.
      Distinct protein spots in the beer and wort proteomes were identified using
      Matrix-assisted laser desorption-ionization time-of-flight mass spectrometry
      (MALDI-TOF-MS) and MS/MS and revealed common beer proteins, such as lipid
      transfer proteins (LTP1 and LTP2), protein Z and amylase-protease inhibitors.
      During fermentation, two protein spots, corresponding to LTP2, disappeared, while
      three protein spots were exclusively found in beer. These three proteins, all
      derived from yeast, were identified as cell wall associated proteins, that is
      Exg1 (an exo-beta-1,3-glucanase), Bgl2 (an endo-beta-1,2-glucanase), and Uth1 (a
      cell wall biogenesis protein). CONCLUSION: Yeast strain dependent changes in the
      immature beer proteome were identified, i.e. Bgl2 was present in beer brewed with
      KVL011, while lacking in WLP001 beer.

PMID- 24079910
TI  - Evaluation of remote monitoring of parturition in dairy cattle as a new tool for
      calving management.
AB  - BACKGROUND: Proper calving management of dairy herds is a crucial aspect of the
      bovine life cycle, as it has profound effects on calf viability and on the post
      partum course of the dam. The objectives of this study were to monitor the
      calving process through the use of a remote alarm system and to determine the
      impact of prompt emergency obstetric procedures in case of dystocia for the
      prevention of stillbirths and post-partum reproductive pathologies, and for
      improving herd fertility. Six groups of experimental animals were studied:
      monitored heifers (n = 60) and multiparous cows (n = 60) were compared with non
      observed animals (n = 60 heifers and n = 60 multiparous) giving birth during the
      same time period and housed in the calving barn, and with unmonitored animals
      placed in a dry zone (n = 240 heifers and n = 112 multiparous cows). RESULTS: The
      incidence of dystocia ranged from a minimum of 23.4% (monitored multiparous cows)
      to a maximum of 33.3% (monitored heifers), and there were no differences compared
      with control groups. However, the rate of stillbirth was higher in control groups
      than in the monitored groups (P < 0.01). Among both heifers and multiparous cows,
      the incidence of post-partum uterine infections was higher in the unmonitored
      animals both in the calving barn (P < 0.01) and in the dry zone (P < 0.05)
      compared with monitored animals. Among both heifers and multiparous cows, the
      control groups showed higher rates of foetal membrane retention than did the
      monitored groups (P < 0.001). The calving-to-conception interval was shorter; in
      particular, observed heifers showed a significant advantage of approximately 46
      days compared with the unmonitored group (P < 0.001) and 32 days compared with
      the group in the calving barn (P < 0.05). Multiparous cows also had a reduction
      in the number of days open. CONCLUSIONS: The remote alarm system used to monitor
      the calving process assured the prompt presence of personnel, improving both the
      cow's reproductive efficiency and neonatal viability.

PMID- 24079911
TI  - Feasibility and coverage of implementing intermittent preventive treatment of
      malaria in pregnant women contacting private or public clinics in Tanzania:
      experience-based viewpoints of health managers in Mkuranga and Mufindi districts.
AB  - BACKGROUND: Evidence on healthcare managers' experience on operational
      feasibility of malaria intermittent preventive treatment for malaria during
      pregnancy (IPTp) using sulphadoxine-pyrimethamine (SP) in Africa is
      systematically inadequate. This paper elucidates the perspectives of District
      Council Health Management Team (CHMT)s regarding the feasibility of IPTp with SP
      strategy, including its acceptability and ability of district health care systems
      to cope with the contemporary and potential challenges. METHODS: The study was
      conducted in Mkuranga and Mufindi districts. Data were collected between November
      2005 and December 2007, involving focus group discussion (FGD) with Mufindi CHMT
      and in-depth interviews were conducted with few CHMT members in Mkuranga where it
      was difficult to summon all members for FGD. RESULTS: Participants in both
      districts acknowledged the IPTp strategy, considering the seriousness of malaria
      in pregnancy problem; government allocation of funds to support healthcare staff
      training programmes in focused antenatal care (fANC) issues, procuring essential
      drugs distributed to districts, staff remuneration, distribution of fANC
      guidelines, and administrative activities performed by CHMTs. The identified
      weaknesses include late arrival of funds from central level weakening CHMT's
      performance in health supervision, organising outreach clinics, distributing
      essential supplies, and delivery of IPTp services. Participants anticipated the
      public losing confidence in SP for IPTp after government announced artemither
      lumefantrine (ALu) as the new first-line drug for uncomplicated malaria replacing
      SP. Role of private healthcare staff in IPTp services was acknowledged cautiously
      because CHMTs rarely supplied private clinics with SP for free delivery in fear
      that clients would be required to pay for the SP contrary to government policy.
      In Mufindi, the District Council showed a strong political support by
      supplementing ANC clinics with bottled water; in Mkuranga such support was not
      experienced. A combination of health facility understaffing, water scarcity and
      staff non-adherence to directly observed therapy instructions forced healthcare
      staff to allow clients to take SP at home. Need for investigating in improving
      adherence to IPTp administration was emphasised. CONCLUSION: High acceptability
      of the IPTp strategy at district level is meaningless unless necessary support is
      assured in terms of number, skills and motivation of caregivers and availability
      of essential supplies.

PMID- 24079912
TI  - Kinetic and thermodynamic rationale for suberoylanilide hydroxamic acid being a
      preferential human histone deacetylase 8 inhibitor as compared to the
      structurally similar ligand, trichostatin a.
AB  - Of the different hydroxamate-based histone deacetylase (HDAC) inhibitors,
      suberoylanilide hydroxamic acid (SAHA) has been approved by the Food and Drug
      Administration for the treatment of T-cell lymphoma. Interestingly, a
      structurally similar inhibitor, trichostatin A (TSA), which has a higher in vitro
      inhibitory potency against HDAC8, reportedly shows poor efficacy in clinical
      settings. To gain molecular insight into this discriminatory feature, we
      performed transient kinetic and isothermal titration calorimetric studies for the
      interaction of SAHA and TSA with the recombinant form of human HDAC8. The
      transient kinetic data revealed that the binding of both inhibitors to the enzyme
      showed biphasic profiles, which represented an initial encounter of the enzyme
      with the inhibitor followed by the isomerization of the transient enzyme
      inhibitor complexes. The temperature-dependent transient kinetic studies with
      these inhibitors revealed that the bimolecular process is primarily dominated by
      favorable enthalpic changes, as opposed to the isomerization step, which is
      solely contributed by entropic changes. The standard binding enthalpy (DeltaH
      degrees ) of SAHA, deduced from the transient kinetic as well as the isothermal
      titration calorimetric experiments, was 2-3 kcal/mol higher than that of TSA. The
      experimental data presented herein suggest that SAHA serves as a preferential
      (target-specific and -selective) HDAC8 inhibitor as compared to TSA. Arguments
      that the detailed kinetic and thermodynamic studies may guide the rational design
      of HDAC inhibitors as therapeutic agents are presented. 

PMID- 24079913
TI  - Triclosan alters antimicrobial and inflammatory responses of epithelial cells.
AB  - Periodontal diseases are a class of pathologies wherein oral microbes induce
      harmful immune responses in a susceptible host. Therefore, an agent that can both
      reduce microbial burden and lessen pathogenesis of localized inflammation would
      have beneficial effects in periodontal disease; 2,4,4-trichloro-2-hydroxydiphenyl
      ether [triclosan] is currently used in oral care products owing to broad spectrum
      antimicrobial and anti-inflammatory properties. OBJECTIVE: To determine effects
      of triclosan on the response of oral epithelial cells to stimulation with the
      inflammatory microbial product lipopolysaccharide (LPS), a ligand for toll-like
      receptor 4 [TLR4]. MATERIALS/METHODS: Primary human oral epithelial cells were
      stimulated with LPS in the presence and/or absence of triclosan after which
      expression of pro-inflammatory cytokines, beta-defensins, micro-RNAs [miRNAs], or
      TLR-signaling pathway proteins were evaluated. RESULTS: Here, we demonstrate that
      triclosan is a potent inhibitor of oral epithelial cell LPS-induced pro
      inflammatory responses by inducing miRNA regulation of the TLR-signaling pathway.
      Triclosan was not a pan-suppresser of oral epithelial cell responses as beta
      defensin 2 [betaD2] and betaD3 were upregulated by triclosan following LPS
      stimulation. CONCLUSIONS: These data demonstrate both a novel antimicrobial
      mechanism by which triclosan improves plaque control and an additional anti
      inflammatory property, which could have beneficial effects in periodontal disease
      resolution.

PMID- 24079915
TI  - Experimental study of ultrasonic beam sectors for energy conversion into Lamb
      waves and Rayleigh waves.
AB  - When a bounded beam is incident on an immersed plate Lamb waves or Rayleigh waves
      can be generated. Because the amplitude of a bounded beam is not constant along
      its wave front, a specific beam profile is formed that influences the local
      efficiency of energy conversion of incident sound into Lamb waves or Rayleigh
      waves. Understanding this phenomenon is important for ultrasonic immersion
      experiments of objects because the quality of such experiments highly depends on
      the amount of energy transmitted into the object. This paper shows by means of
      experiments based on monochromatic Schlieren photography that the area within the
      bounded beam responsible for Lamb wave generation differs from that responsible
      for Rayleigh wave generation. Furthermore it provides experimental verification
      of an earlier numerical study concerning Rayleigh wave generation. 

PMID- 24079914
TI  - Hyperglycemia induced and intrinsic alterations in type 2 diabetes-derived
      osteoclast function.
AB  - Periodontal disease-associated alveolar bone loss is a comorbidity of type-2
      diabetes, where the roles of osteoclasts are poorly understood. OBJECTIVE: To
      evaluate osteoclast differentiation and function in the context of type-2
      diabetes. MATERIALS AND METHODS: Bone marrow-derived osteoclasts from db/db mice,
      a model of type-2-diabetes, as well as human osteoclasts derived from peripheral
      blood of individuals with type-2-diabetes were evaluated for differentiation,
      resorption, and soluble mediator expression. RESULTS: While db/db mice were
      hyperglycemic at time of cell harvest, human participants were glycemically
      controlled. Although db/db cultures resulted in a higher number of larger
      osteoclasts, individual cell receptor activator of nuclear factor kappaB ligand
      (RANKL)-mediated bone resorption was similar to that observed in diabetes-free
      osteoclasts. Osteoclasts derived from individuals with type-2-diabetes
      differentiated similarly to controls with again no difference in bone resorbing
      capacity. Murine and human type-2-diabetes cultures both displayed inhibition of
      lipopolysaccharide (LPS)-induced deactivation and increased pro-osteoclastogenic
      mediator expression. CONCLUSIONS: Hyperglycemia plays a role in aberrant
      osteoclast differentiation leading to an increased capacity for bone resorption.
      Osteoclasts derived from murine models of and individuals with type-2-diabetes
      are unable to be inhibited by LPS, again leading to increased capacity for bone
      resorption. Here, environmental and intrinsic mechanisms associated with the
      increased alveolar bone loss observed in periodontal patients with type-2
      diabetes are described.

PMID- 24079916
TI  - The mirror neuron system contributes to social responding.

PMID- 24079917
TI  - Improved multitasking following prefrontal tDCS.
AB  - We have a limited capacity for mapping sensory information onto motor responses.
      This processing bottleneck is thought to be a key factor in determining our
      ability to make two decisions simultaneously - i.e., to multitask (Pashler, 1984,
      1994; Welford, 1952). Previous functional imaging research (Dux, Ivanoff,
      Asplund, & Marois, 2006; Dux et al., 2009) has localised this bottleneck to the
      posterior lateral prefrontal cortex (pLPFC) of the left hemisphere. Currently,
      however, it is unknown whether this region is causally involved in multitasking
      performance. We investigated the role of the left pLPFC in multitasking using
      transcranial direct current stimulation (tDCS). The behavioural paradigm included
      single- and dual-task trials, each requiring a speeded discrimination of visual
      stimuli alone, auditory stimuli alone, or both visual and auditory stimuli.
      Reaction times for single- and dual-task trials were compared before, immediately
      after, and 20 min after anodal stimulation (excitatory), cathodal stimulation
      (inhibitory), or sham stimulation. The cost of responding to the two tasks (i.e.,
      the reduction in performance for dual- vs single-task trials) was significantly
      reduced by cathodal stimulation, but not by anodal or sham stimulation. Overall,
      the results provide direct evidence that the left pLPFC is a key neural locus of
      the central bottleneck that limits an individual's ability to make two simple
      decisions simultaneously.

PMID- 24079918
TI  - Association of job strain with working hours, shift-dependent perceived workload,
      sleepiness and recovery.
AB  - We explored the relationship of job strain with working hours, shift-dependent
      perceived workload, sleepiness and recovery. Nurses/nursing assistants (n = 95)
      were recruited from wards that belonged to either the top (high-strain group,
      HJS) or the bottom (low-strain group, LJS) job strain quartiles of a Job Content
      Questionnaire survey of employees in five health care districts and four cities
      in Finland. Three-week field measurements during naturally occurring shift
      schedules and a subset of pre-selected shift arrangements consisted of the
      Karolinska Sleepiness Scale, perceived workload and recovery. The HJS group (n =
      42) had more single days off and quick returns than the LJS group (n = 53, p <
      0.01), and both mental workload and physical workload were rated as higher (p <
      0.01). During naturally occurring shift arrangements, severe sleepiness was more
      common in the HJS group only in quick returns (p = 0.04) and the HJS group
      recovered on average more poorly from work after all shifts (p = 0.01) and
      morning shifts (p = 0.02). During pre-selected shift arrangements, the
      differences between the groups were only minor. In conclusion, job strain-related
      differences in sleepiness and recovery were mostly attributable to differences in
      shift arrangements. 

PMID- 24079919
TI  - Design options for a more sustainable urban water environment.

PMID- 24079920
TI  - Advanced nanocluster ion source based on high-power impulse magnetron sputtering
      and time-resolved measurements of nanocluster formation.
AB  - We developed a new nanocluster (NC) ion source based on the high-power impulse
      magnetron sputtering (HiPIMS) technique coupled with a gas flow cell reactor.
      Silver NC anions (Ag(n)(-)) with a maximum intensity of 5.5 nA (Ag11(-)) are
      generated with the size ranging from the atomic anion to the 70-mer, which is
      well-controlled by simply adjusting the peak power and repetition rate of the
      HiPIMS. By time-resolved density profiles of Ag(n)(-), we find that the ion beam
      generated by HiPIMS is characterized by individual 100 ms duration "bunches"
      below a repetition rate of 10 Hz, which is well-thermalized with a group velocity
      of 5 m/s. The high intensity of the NCs is attributable to the high ionization
      fraction by this HiPIMS ion source, while the underlying mechanism of the
      flexible size tuning of the ion source is understood by time-resolved mass
      spectrometry coupled with the sequential growth mechanism; the increment of the
      density of the target species in the bunches with the peak power and the
      overlapping of the bunches with the repetition rate cause the formation of large
      NCs.

PMID- 24079921
TI  - Contrasting key roles of Ruppia cirrhosa in a southern Mediterranean lagoon:
      reservoir for both biodiversity and harmful species and indicator of lagoon
      health status.
AB  - The distribution of Ruppia cirrhosa meadow density and its epiphytic organisms in
      relation with environmental factors were studied in summer 2011 at five stations
      in the Ghar El Melh lagoon (GML; southern Mediterranean Sea). Eleven epiphytic
      groups were recognised among which diatoms and dinoflagellates were the dominant
      groups and greatest contributors to temporal dissimilarity. An overwhelming
      concentrations of harmful microalgae was recorded, mainly represented by the
      toxic dinoflagellate Prorocentrum lima with maximal concentrations attaining 6 *
      10(5)cells 100g(-1) of Ruppia fresh weight. The epifauna community accounted for
      only 1.4% of total epiphyte abundance and was comprised predominantly of
      nematodes (47.51%), ciliates (32.59%), fish eggs (7.2%) and larvae (4.95%).
      PERMANOVA analyses revealed a significant spatio-temporal variation of all
      epiphytic groups (p<0.01). In this study, R. cirrhosa and its epiphytes were
      studied as potential early warning indicators of the health status of GML waters.

PMID- 24079922
TI  - Impact of milk fish farming in the tropics on potentially pathogenic vibrios.
AB  - Ratios of sucrose-negative to sucrose-positive vibrios on TCBS agar (suc-/suc+)
      indicate the abundance of potential human pathogenic non-cholera vibrios in
      coastal mariculture environments of the Lingayen Gulf (Philippines. In guts of
      adult maricultured milkfish (Chanos chanos) of suc- vibrios reached extreme peak
      values ranging between 2 and 545 million per g wet weight. Suc- vibrios
      outnumbered suc+ vibrios in anoxic sediments, too, and were rarely predominant in
      coastal waters or in oxidized sediments. Suc-/suc+ ratios in sediments increased
      toward the mariculture areas with distance from the open sea at decreasing redox
      potentials. There is circumstantial evidence that suc- vibrios can be dispersed
      from mariculture areas to adjacent environments including coral reefs. An
      immediate human health risk by pathogenic Vibrio species is discounted, since
      milkfish guts contained mainly members of the Enterovibrio group. A
      representative isolate of these contained proteolytic and other virulence
      factors, but no genes encoding toxins characteristic of clinical Vibrio species.

PMID- 24079923
TI  - Converting from d to r to z when the design uses extreme groups, dichotomization,
      or experimental control.
AB  - Meta-analyses of the relationship between 2 continuous variables sometimes
      involves conversions between different effect sizes, but methodological
      literature offers conflicting guidance about how to make such conversions. This
      article provides methods for converting from a standardized mean difference to a
      correlation coefficient (and from there to Fisher's z) under 3 types of study
      designs: extreme groups, dichotomization of a continuous variable, and controlled
      experiments. Also provided are formulas and recommendations regarding how the
      sampling variance of effect size statistics should be estimated in each of these
      cases. The conversion formula for extreme groups designs, originally due to Feldt
      (1961), can be viewed as a generalization of Hunter and Schmidt's (1990) method
      for dichotomization designs. A simulation study examines the finite-sample
      properties of the proposed methods. The conclusion highlights areas where current
      guidance in the literature should be amended or clarified.

PMID- 24079924
TI  - Why the resistance to statistical innovations? Bridging the communication gap.
AB  - While quantitative methodologists advance statistical theory and refine
      statistical methods, substantive researchers resist adopting many of these
      statistical innovations. Traditional explanations for this resistance are
      reviewed, specifically a lack of awareness of statistical developments, the
      failure of journal editors to mandate change, publish or perish pressures, the
      unavailability of user friendly software, inadequate education in statistics, and
      psychological factors. Resistance is reconsidered in light of the complexity of
      modern statistical methods and a communication gap between substantive
      researchers and quantitative methodologists. The concept of a Maven is introduced
      as a means to bridge the communication gap. On the basis of this review and
      reconsideration, recommendations are made to improve communication of statistical
      innovations.

PMID- 24079925
TI  - Robust mediation analysis based on median regression.
AB  - Mediation analysis has many applications in psychology and the social sciences.
      The most prevalent methods typically assume that the error distribution is normal
      and homoscedastic. However, this assumption may rarely be met in practice, which
      can affect the validity of the mediation analysis. To address this problem, we
      propose robust mediation analysis based on median regression. Our approach is
      robust to various departures from the assumption of homoscedasticity and
      normality, including heavy-tailed, skewed, contaminated, and heteroscedastic
      distributions. Simulation studies show that under these circumstances, the
      proposed method is more efficient and powerful than standard mediation analysis.
      We further extend the proposed robust method to multilevel mediation analysis,
      and demonstrate through simulation studies that the new approach outperforms the
      standard multilevel mediation analysis. We illustrate the proposed method using
      data from a program designed to increase reemployment and enhance mental health
      of job seekers.

PMID- 24079926
TI  - Computing confidence intervals for standardized regression coefficients.
AB  - With fixed predictors, the standard method (Cohen, Cohen, West, & Aiken, 2003, p.
      86; Harris, 2001, p. 80; Hays, 1994, p. 709) for computing confidence intervals
      (CIs) for standardized regression coefficients fails to account for the sampling
      variability of the criterion standard deviation. With random predictors, this
      method also fails to account for the sampling variability of the predictor
      standard deviations. Nevertheless, under some conditions the standard method will
      produce CIs with accurate coverage rates. To delineate these conditions, we used
      a Monte Carlo simulation to compute empirical CI coverage rates in samples drawn
      from 36 populations with a wide range of data characteristics. We also computed
      the empirical CI coverage rates for 4 alternative methods that have been
      discussed in the literature: noncentrality interval estimation, the delta method,
      the percentile bootstrap, and the bias-corrected and accelerated bootstrap. Our
      results showed that for many data-parameter configurations--for example, sample
      size, predictor correlations, coefficient of determination (R2), orientation of
      beta with respect to the eigenvectors of the predictor correlation matrix, RX-
      the standard method produced coverage rates that were close to their expected
      values. However, when population R2 was large and when beta approached the last
      eigenvector of RX, then the standard method coverage rates were frequently below
      the nominal rate (sometimes by a considerable amount). In these conditions, the
      delta method and the 2 bootstrap procedures were consistently accurate. Results
      using noncentrality interval estimation were inconsistent. In light of these
      findings, we recommend that researchers use the delta method to evaluate the
      sampling variability of standardized regression coefficients.

PMID- 24079927
TI  - Manifest variable path analysis: potentially serious and misleading consequences
      due to uncorrected measurement error.
AB  - Despite clear evidence that manifest variable path analysis requires highly
      reliable measures, path analyses with fallible measures are commonplace even in
      premier journals. Using fallible measures in path analysis can cause several
      serious problems: (a) As measurement error pervades a given data set, many path
      coefficients may be either over- or underestimated. (b) Extensive measurement
      error diminishes power and can prevent invalid models from being rejected. (c)
      Even a little measurement error can cause valid models to appear invalid. (d)
      Differential measurement error in various parts of a model can change the
      substantive conclusions that derive from path analysis. (e) All of these problems
      become increasingly serious and intractable as models become more complex.
      Methods to prevent and correct these problems are reviewed. The conclusion is
      that researchers should use more reliable measures (or correct for measurement
      error in the measures they do use), obtain multiple measures for use in latent
      variable modeling, and test simpler models containing fewer variables.

PMID- 24079928
TI  - Treatment effects in randomized longitudinal trials with different types of
      nonignorable dropout.
AB  - Randomized longitudinal designs are commonly used in psychological and medical
      studies to investigate the treatment effect of an intervention or an experimental
      drug. Traditional linear mixed-effects models for randomized longitudinal designs
      are limited to maximum-likelihood methods that assume data are missing at random
      (MAR). In practice, because longitudinal data are often likely to be missing not
      at random (MNAR), the traditional mixed-effects model might lead to biased
      estimates of treatment effects. In such cases, an alternative approach is to
      utilize pattern-mixture models. In this article, a Monte Carlo simulation study
      compares the traditional mixed-effects model and 2 different approaches to
      pattern-mixture models (i.e., the differencing-averaging method and the averaging
      differencing method) across different missing mechanisms (i.e., MAR, random
      coefficient-dependent MNAR, or outcome-dependent MNAR) and different types of
      treatment-condition-based missingness. Results suggest that the traditional mixed
      effects model is well suited for analyzing data with the MAR mechanism whereas
      the proposed pattern-mixture averaging-differencing model has the best overall
      performance for analyzing data with the MNAR mechanism. No method was found that
      could provide unbiased estimates under every missing mechanism, leading to a
      practical suggestion that researchers need to consider why data are missing and
      should also consider performing a sensitivity analysis to ascertain the extent to
      which their results are consistent across various missingness assumptions.
      Applications of different estimation methods are also illustrated using a real
      data example.

PMID- 24079929
TI  - Functional data analysis for dynamical system identification of behavioral
      processes.
AB  - Efficient new technology has made it straightforward for behavioral scientists to
      collect anywhere from several dozen to several thousand dense, repeated
      measurements on one or more time-varying variables. These intensive longitudinal
      data (ILD) are ideal for examining complex change over time but present new
      challenges that illustrate the need for more advanced analytic methods. For
      example, in ILD the temporal spacing of observations may be irregular, and
      individuals may be sampled at different times. Also, it is important to assess
      both how the outcome changes over time and the variation between participants'
      time-varying processes to make inferences about a particular intervention's
      effectiveness within the population of interest. The methods presented in this
      article integrate 2 innovative ILD analytic techniques: functional data analysis
      and dynamical systems modeling. An empirical application is presented using data
      from a smoking cessation clinical trial. Study participants provided 42 daily
      assessments of pre-quit and post-quit withdrawal symptoms. Regression splines
      were used to approximate smooth functions of craving and negative affect and to
      estimate the variables' derivatives for each participant. We then modeled the
      dynamics of nicotine craving using standard input-output dynamical systems
      models. These models provide a more detailed characterization of the post-quit
      craving process than do traditional longitudinal models, including information
      regarding the type, magnitude, and speed of the response to an input. The
      results, in conjunction with standard engineering control theory techniques,
      could potentially be used by tobacco researchers to develop a more effective
      smoking intervention.

PMID- 24079930
TI  - A discrete-time Multiple Event Process Survival Mixture (MEPSUM) model.
AB  - Traditional survival analysis was developed to investigate the occurrence and
      timing of a single event, but researchers have recently begun to ask questions
      about the order and timing of multiple events. A multiple event process survival
      mixture model is developed here to analyze nonrepeatable events measured in
      discrete-time that may occur at the same point in time. Building on both
      traditional univariate survival analysis and univariate survival mixture
      analysis, the model approximates the underlying multivariate distribution of
      hazard functions via a discrete-point finite mixture in which the mixing
      components represent prototypical patterns of event occurrence. The model is
      applied in an empirical analysis concerning transitions to adulthood, where the
      events under study include parenthood, marriage, beginning full-time work, and
      obtaining a college degree. Promising opportunities, as well as possible
      limitations of the model and future directions for research, are discussed.

PMID- 24079931
TI  - Measures of metacognition on signal-detection theoretic models.
AB  - Analyzing metacognition, specifically knowledge of accuracy of internal
      perceptual, memorial, or other knowledge states, is vital for many strands of
      psychology, including determining the accuracy of feelings of knowing and
      discriminating conscious from unconscious cognition. Quantifying metacognitive
      sensitivity is however more challenging than quantifying basic stimulus
      sensitivity. Under popular signal-detection theory (SDT) models for stimulus
      classification tasks, approaches based on Type II receiver-operating
      characteristic (ROC) curves or Type II d-prime risk confounding metacognition
      with response biases in either the Type I (classification) or Type II
      (metacognitive) tasks. A new approach introduces meta-d': The Type I d-prime that
      would have led to the observed Type II data had the subject used all the Type I
      information. Here, we (a) further establish the inconsistency of the Type II d
      prime and ROC approaches with new explicit analyses of the standard SDT model and
      (b) analyze, for the first time, the behavior of meta-d' under nontrivial
      scenarios, such as when metacognitive judgments utilize enhanced or degraded
      versions of the Type I evidence. Analytically, meta-d' values typically reflect
      the underlying model well and are stable under changes in decision criteria;
      however, in relatively extreme cases, meta-d' can become unstable. We explore
      bias and variance of in-sample measurements of meta-d' and supply MATLAB code for
      estimation in general cases. Our results support meta-d' as a useful measure of
      metacognition and provide rigorous methodology for its application. Our
      recommendations are useful for any researchers interested in assessing
      metacognitive accuracy.

PMID- 24079933
TI  - Controlling the maximum familywise Type I error rate in analyses of multivariate
      experiments.
AB  - Multivariate experiments are often analyzed by multistage multiple-comparison
      procedures (MCPs) that prohibit univariate testing on individual dependent
      variables if an overall multivariate analysis of variance (MANOVA) test fails to
      reject the relevant overall null hypothesis. Although the sole function of the
      MANOVA test in such analyses is to control the overall Type I error rate, it is
      known that the most popular MANOVA-protected MCPs do not control the maximum
      familywise error rate (MFWER). In this article, we show that the MFWER associated
      with standard MANOVA-protected MCPs can be so large that the protection provided
      by the initial MANOVA test is illusory. We show that the MFWER can be controlled
      nonconservatively with modified protected MCPs and with single-stage MCPs that
      allow for the construction of simultaneous confidence intervals on effect sizes.
      We argue that, given the ease with which these MCPs can be implemented, there is
      no justification for continued use of the standard procedures.

PMID- 24079932
TI  - A trifactor model for integrating ratings across multiple informants.
AB  - Psychologists often obtain ratings for target individuals from multiple
      informants such as parents or peers. In this article we propose a trifactor model
      for multiple informant data that separates target-level variability from
      informant-level variability and item-level variability. By leveraging item-level
      data, the trifactor model allows for examination of a single trait rated on a
      single target. In contrast to many psychometric models developed for multitrait
      multimethod data, the trifactor model is predominantly a measurement model. It is
      used to evaluate item quality in scale development, test hypotheses about sources
      of target variability (e.g., sources of trait differences) versus informant
      variability (e.g., sources of rater bias), and generate integrative scores that
      are purged of the subjective biases of single informants.

PMID- 24079934
TI  - Keyhole acceleration for magnetic resonance acoustic radiation force imaging (MR
      ARFI).
AB  - MR ARFI measures the displacement induced by the ultrasonic radiation force and
      provides the location of the focal spot without significant heating effects.
      Displacements maps obtained with MR ARFI provide an indirect estimation of the
      acoustic beam intensity at the target. This measure is essential for dose
      estimation prior to focused ultrasound treatments (FUS) and adaptive focusing
      procedures of MR-guided transcranial and transribs FUS. In the latter case, the
      beam correction is achieved by maximizing the displacement at focus. A
      significant number of serial MR ARFI images are required and thus, a partial k
      space updating method, such as keyhole appears as a method of choice. The purpose
      of this work is to demonstrate via simulations and experiments the efficiency of
      the keyhole technique combined with a two-dimensional spin-echo MR ARFI pulse
      sequence. The method was implemented in an ex vivo calf brain taking advantage of
      the a priori knowledge of the focal spot profile. The coincidence of the phase
      encoding axis with the longest axis of the focal spot makes the best use of the
      technique. Our approach rapidly provides the focal spot localization with
      accuracy, and with a substantial increase to the signal-to-noise ratio, while
      reducing ultrasound energy needed during MR-guided adaptive focusing procedures. 

PMID- 24079935
TI  - Pioglitazone counteracts the tumor necrosis factor-alpha inhibition of follicle
      stimulating hormone-induced follicular development and estradiol production in an
      in vitro mouse preantral follicle culture system.
AB  - BACKGROUND: Polycystic ovary syndrome (PCOS) is a common endocrine disorder in
      women of reproductive age and is characterized by chronic anovulation. Insulin
      resistance may be a key component of the pathogenesis of this disorder.
      Pioglitazone is a thiazolidinedione derivative that acts by improving insulin
      resistance via the peroxisome proliferator-activated receptor-gamma (PPAR-gamma)
      pathway. Reportedly, pioglitazone improves the anovulation status in patients
      with PCOS. In the present study, we examined whether pioglitazone directly
      affects ovarian follicular development and steroidogenesis using in vitro mouse
      preantral follicle culture system. METHODS: An isolated individual in vitro mouse
      preantral follicle culture was used to test the effects of pioglitazone on the
      follicle development and steroidogenesis. Tumor necrosis factor-alpha (TNF
      alpha), which plays a role in insulin resistance, has been reported to inhibit
      the follicle stimulating hormone (FSH)-induced follicular development and
      steroidogenesis in an in vitro mouse preantral follicle culture system.
      Therefore, we examined whether pioglitazone counteracts these effects by TNF
      alpha. We assessed the follicle diameter and follicle survival and antral-like
      cavity formation rates, the 17beta-estradiol (E2) levels in the culture medium,
      and the ovulation rate using the in vitro preantral follicle culture. RESULTS:
      Pioglitazone treatment counteracted the inhibition of TNF-alpha in FSH-induced
      follicle development in a dose-dependent manner. Pioglitazone, at a concentration
      of 5 MUM, which was the minimum effective concentration, significantly
      counteracted the inhibition of TNF-alpha in FSH-induced follicle survival (29
      versus 56%, P < 0.05), antral-like cavity formation (29 versus 48%, P < 0.05), E2
      concentration in the culture medium (mean +/- SEM = 21 +/- 1 versus mean +/- SEM
      = 27 +/- 1 pg/mL, P < 0.05), and human chorionic gonadotropin-induced ovulation
      rate (9 versus 28%, P < 0.05). CONCLUSIONS: Pioglitazone counteracted the
      inhibition by TNF-alpha on FSH-induced follicle development and steroidogenesis
      in the in vitro mouse preantral follicle culture. The results suggest that
      pioglitazone may directly affect the follicular development and steroidogenesis.

PMID- 24079936
TI  - Uterine fibroid: the burden borne by African American women.

PMID- 24079937
TI  - The Affordable Care Act: addressing the unique health needs of women.

PMID- 24079938
TI  - Systematic review with meta-analysis: race-specific effects of alcohol and
      tobacco on the risk of oesophageal squamous cell carcinoma.
AB  - BACKGROUND: Oesophageal squamous cell carcinoma (OSCC) is associated with alcohol
      use, tobacco use and African or Asian descent. However, little is known about how
      racial background modifies the effects of alcohol or tobacco. AIM: To investigate
      how racial and geographical background modifies the effect of alcohol and tobacco
      on OSCC via a systematic review and meta-analysis of published literature.
      METHODS: We performed a literature search in multiple online databases regardless
      of language. Eligible studies were population-based assessments of the effect of
      tobacco and/or alcohol on the risk of OSCC allowing stratification by race. The
      quality of studies was assessed by the Newcastle-Ottawa Scale. Meta-analyses were
      performed to estimate summary effects using random effect models. RESULTS:
      Systematic review identified 9668 unique citations of which 34 were eligible. The
      majority were of high quality. The effect of current smoking vs. never-smoking
      was weaker among Asians than among Europeans [European: odds ratio (OR) = 4.21,
      95% confidence interval (CI) 3.13, 5.66; Asian: OR = 2.31, 95% CI 1.78, 2.99],
      with the 95% CIs not crossing, indicating statistical significance. Asians also
      trended towards weaker effects of long-duration cigarette use and of heavy daily
      cigarette use. There was no difference in the effect of alcohol on OSCC risk by
      race. CONCLUSIONS: Contrary to our hypothesis, a weaker effect of tobacco for
      OSCC was observed among Asians than among Europeans. Differences in other factors
      must explain the higher incidence of OSCC among Asians. More studies are needed
      to understand the cause of the disparate incidence of OSCC between races.

PMID- 24079939
TI  - Structure of a Clostridium botulinum C143S thiaminase I/thiamin complex reveals
      active site architecture .
AB  - Thiaminases are responsible for the degradation of thiamin and its metabolites.
      Two classes of thiaminases have been identified based on their three-dimensional
      structures and their requirements for a nucleophilic second substrate. Although
      the reactions of several thiaminases have been characterized, the physiological
      role of thiamin degradation is not fully understood. We have determined the three
      dimensional X-ray structure of an inactive C143S mutant of Clostridium botulinum
      (Cb) thiaminase I with bound thiamin at 2.2 A resolution. The C143S/thiamin
      complex provides atomic level details of the orientation of thiamin upon binding
      to Cb-thiaminase I and the identity of active site residues involved in substrate
      binding and catalysis. The specific roles of active site residues were probed by
      using site directed mutagenesis and kinetic analyses, leading to a detailed
      mechanism for Cb-thiaminase I. The structure of Cb-thiaminase I is also compared
      to the functionally similar but structurally distinct thiaminase II.

PMID- 24079941
TI  - Photoactivated cyclization of aryl-containing enediynes coated gold
      nanoparticles: enhancement of the DNA cleavage ability of enediynes.
AB  - Two novel enediynes containing an aromatic ring and substituted by two thiol
      functions as end-groups were designed and studied as functionalizing agent of
      gold nanoparticles. Phototriggered cyclization of the capping agent under UV
      visible irradiation was investigated. Interestingly, the length of the thiol
      substituted chain was shown to influence significantly the cyclization rate.
      Depending on the length of the spacer, either polymerization or simple
      cyclization of the coating agent was evidenced. The present study underscores the
      possibility of finely controlling the fate of the coating agent
      (polymerization/cyclization). Nanocomposites were characterized by UV-visible
      absorption spectroscopy, dynamic light scattering (DLS) technique and
      transmission electron microscopy (TEM) measurements. Finally, the ability of the
      colloidal solutions to induce photoinitiated damages to PcDNA3 supercoiled DNA
      was evaluated. Interestingly, an increase as high as 50% of the DNA cleavage
      could be registered when adding enediynes-capped gold nanoparticles to solutions
      of enediynes. In particular, the enhancement of DNA scission was observed in both
      thermal and photochemical activation modes. 

PMID- 24079940
TI  - Single step reconstitution of multifunctional high-density lipoprotein-derived
      nanomaterials using microfluidics.
AB  - High-density lipoprotein (HDL) is a natural nanoparticle that transports
      peripheral cholesterol to the liver. Reconstituted high-density lipoprotein
      (rHDL) exhibits antiatherothrombotic properties and is being considered as a
      natural treatment for cardiovascular diseases. Furthermore, HDL nanoparticle
      platforms have been created for targeted delivery of therapeutic and diagnostic
      agents. The current methods for HDL reconstitution involve lengthy procedures
      that are challenging to scale up. A central need in the synthesis of rHDL, and
      multifunctional nanomaterials in general, is to establish large-scale production
      of reproducible and homogeneous batches in a simple and efficient fashion. Here,
      we present a large-scale microfluidics-based manufacturing method for single-step
      synthesis of HDL-mimicking nanomaterials (MUHDL). MUHDL is shown to have the same
      properties (e.g., size, morphology, bioactivity) as conventionally reconstituted
      HDL and native HDL. In addition, we were able to incorporate simvastatin (a
      hydrophobic drug) into MUHDL, as well as gold, iron oxide, quantum dot
      nanocrystals or fluorophores to enable its detection by computed tomography (CT),
      magnetic resonance imaging (MRI), or fluorescence microscopy, respectively. Our
      approach may contribute to effective development and optimization of lipoprotein
      based nanomaterials for medical imaging and drug delivery. 

PMID- 24079943
TI  - Source of temperature and pressure pulsations during sessile droplet evaporation
      into multicomponent atmospheres.
AB  - During sessile droplet evaporation, studies with IR thermography and shadowgraphs
      have indicated temperature pulsations. We confirm those observations with
      microthermocouples, but microthermocouples also indicate temperature pulsations
      in the atmosphere of the droplet. The pressure in this atmosphere pulsated as
      well and was correlated with the temperature pulsations in the droplet. Also, we
      find that if a droplet evaporates into its own vapor, there are no temperature or
      pressure pulsations. The pulsations occur only if the droplet evaporates into an
      atmosphere with a component having a heat of solution with the droplet when it
      adsorbs-absorbs. None of the currently proposed mechanisms for the temperature
      pulsations provide an explanation for the coupling between the temperature
      pulsations in the droplet and the vapor-phase pressure pulsations, and for the
      absence of the pulsations when the system is single-component. As a mechanism for
      the pulsations, we propose that when a droplet is exposed to an atmosphere
      containing a component that has a heat of solution with the droplet, energy will
      be released from adsorption-absorption. This energy will cause pulsations in the
      evaporation flux, and these pulsations could cause the observed temperature and
      pressure pulsations. We examine this mechanism by showing that, if the measured
      temperature pulsations in a water droplet exposed to a methanol atmosphere are
      used as the input to a theory of evaporation kinetics (statistical rate theory),
      the pressure pulsations of the water vapor in the methanol atmosphere are
      predicted and agree with those measured with a quadrupole mass analyzer. When the
      inputs and outputs are reversed in the theory, we find that the temperature
      pulsations in the droplet are correctly predicted from the measured water vapor
      pulsations in the atmosphere. 

PMID- 24079942
TI  - Investigation of the structural organization of cationic nanoemulsion/antisense
      oligonucleotide complexes.
AB  - Atomic force microscopy image analysis and energy dispersive X-ray diffraction
      experiments were used to investigate the structural organization of cationic
      nanoemulsion/oligonucleotide complexes. Oligonucleotides targeting topoisomerase
      II gene were adsorbed on cationic nanoemulsions obtained by means of spontaneous
      emulsification procedure. Topographical analysis by atomic force microscopy
      allowed the observation of the nanoemulsion/oligonucleotide complexes through
      three-dimensional high-resolution images. Flattening of the oil droplets was
      observed, which was reduced in the complexes obtained at high amount of adsorbed
      oligonucleotides. In such conditions, complexes exhibit droplet size in the 600nm
      range. The oligonucleotides molecules were detected on the surface of the
      droplets, preventing their fusion during aggregation. A lamellar structure
      organization was identified by energy dispersive X-ray diffraction experiments.
      The presence of the nucleic acid molecules led to a disorganization of the lipid
      arrangement and an expansion in the lattice spacing, which was proportional to
      the amount of oligonucleotides added. 

PMID- 24079944
TI  - Photodynamic therapy: a review and its prospective role in the management of oral
      potentially malignant disorders.
AB  - With the unreliability of epithelial dysplasia as a predictor to determine the
      risk of future malignant development, subjectivity associated in evaluating
      dysplasia by pathologists and paucity of biomarkers that could accurately predict
      the progression risks in oral potentially malignant disorders (PMDs), eradication
      of the lesions appears to be the most desirable approach to minimize the risk of
      invasive cancer formation. Interventions, such as surgery and chemoprevention,
      have not shown promising long-term results in the treatment of these lesions, and
      lack of guidelines and general consensus on their management has incited much
      anxiety and doubts in both patients and community clinicians. Topical
      photodynamic therapy (PDT) is a minimally invasive and minimally toxic technique
      that in recent years has shown great promise in the management of PMDs. In this
      review, we describe the historical developments in the field of PDT, its basic
      mechanisms, as well as related clinical studies, and its challenges in the
      management of oral PMDs. Based on its high efficacy and low side effects, its
      high patient acceptance/compliance, the simplicity of the procedure and its
      minimal pretreatment preparation, topical PDT is believed to have potential to
      play an important role in the management of PMDs, especially of the low-grade
      dysplasia. 

PMID- 24079945
TI  - Gaucher disease: chemotactic factors and immunological cell invasion in a mouse
      model.
AB  - Gaucher disease results from mutations in GBA1 that cause functional disruption
      of the encoded lysosomal enzyme, acid beta-glucosidase. The consequent excess
      accumulation of glucosylceramide and glucosylsphingosine in lysosomes is central
      to the disease pathogenesis with classical involvement of macrophage (Mfs)
      lineage cells of visceral organs, bone, or brain. Several studies have implicated
      the increased secretion of chemokines and infiltration of a variety of
      immunological cells into tissues of Gaucher disease patients. Trafficking of
      immunological cells to the sites of inflammation requires the presence of
      chemokines. Although increases of different immunological cells and several
      chemokines are present in Gaucher disease, the specific chemoattractants that
      cause the increased influx of immunological cells are not fully defined. Here,
      increased levels of I-309, MCP-5, CXCL-2, CXCL-9, CXCL-10, CXCL-11, CXCL-13, and
      their corresponding leukocytes, i.e., MOs (monocytes), Mfs, dendritic cells
      (DCs), polymorphonuclear neutrophils (PMNs), and T, and B cells were identified
      in the circulation of mice with Gba1 mutations (D409V/null). Sera from D409V/null
      mice contained chemoattractants for a variety of immunological cells as shown by
      ex vivo chemotaxis studies and by flow cytometry. Enhanced chemotaxis towards
      9V/null sera was found for 9V/null lung-, spleen-, liver-, and bone marrow
      derived Mfs (CD11b(+) F480(+)), PMNs (Gr1(high) CD11b(+)), DCs (CD11c(+)
      CD11b(+)), T lymphocytes (CD3(+) TCRB(+)), and B lymphocytes (B220(+) CD19(+)).
      These data support these chemotactic factors as causative to increased tissue
      infiltration of leukocytes in Gaucher disease.

PMID- 24079946
TI  - Qualitative investigation of barriers to accessing care by people who inject
      drugs in Saskatoon, Canada: perspectives of service providers.
AB  - BACKGROUND: People who inject drugs (PWID) often encounter barriers when
      attempting to access health care and social services. In our previous study
      conducted to identify barriers to accessing care from the perspective of PWIDs in
      Saskatoon, Canada: poverty, lack of personal support, discrimination, and poor
      knowledge and coordination of service providers among other key barriers were
      identified. The purpose of the present investigation was to explore what service
      providers perceive to be the greatest barriers for PWIDs to receive optimal care.
      This study is an exploratory investigation with a purpose to enrich the
      literature and to guide community action. METHODS: Data were collected through
      focus groups with service providers in Saskatoon. Four focus groups were held
      with a total of 27 service providers. Data were transcribed and qualitative
      analysis was performed. As a result, concepts were identified and combined into
      major themes. RESULTS: Four barriers to care were identified by service
      providers: inefficient use of resources, stigma and discrimination, inadequate
      education and the unique and demanding nature of PWIDs. Participants also
      identified many successful services. CONCLUSION: The results from this
      investigation suggest poor utilization of resources, lack of continuing education
      of health care providers on addictions and coping skills with such demanding
      population, and social stigma and disparity. We recommend improvements in
      resource utilization through, for example, case management. In addition,
      sensitivity training and more comprehensive service centers designed to meet
      PWID's complex needs may improve care. However, community-wide commitment to
      addressing injection drug issues will also be required for lasting solutions.

PMID- 24079947
TI  - Interlimb coordination during forward walking is largely preserved in backward
      walking in children with cerebral palsy.
AB  - OBJECTIVE: Limb kinematics in backward walking (BW) are essentially those of
      forward walking (FW) in reverse. It has been argued that subcortical mechanisms
      could underlie both walking modes. METHODS: Therefore, we tested whether
      participants with supraspinal/cortical deficits (i.e. cerebral palsy) show the
      kinematic reversal from FW to BW. 3D gait analysis was performed in 15 children
      with diplegia and 11 children with hemiplegia to record elevation angles of upper
      arm, lower arm, upper leg, lower leg, and foot, and were compared to those of 23
      control subjects. Coordination patterns were compared between FW and BW, and
      elevation angle traces of BW were reversed in time (revBW) and correlated to FW
      traces. RESULTS: The interlimb coordination pattern during BW was largely
      preserved for all groups. The kinematic reversal of the limbs was also present in
      children with cerebral palsy (represented by high correlation coefficients
      between FW and revBW kinematics). CONCLUSIONS: The neural control mechanism of FW
      leading to BW, is preserved in persons with cortical deficits (as in cerebral
      palsy). SIGNIFICANCE: The current results support previous evidence suggesting
      that interlimb locomotor coordination depends mostly on the coupling between
      spinal pattern generators, coordinated by brainstem mechanisms, rather than
      primarily on cortical structures.

PMID- 24079948
TI  - How specific are inhibitory deficits to obsessive-compulsive disorder? A
      neurophysiological comparison with panic disorder.
AB  - OBJECTIVE: Impaired inhibition may perpetuate repetitive symptoms in obsessive
      compulsive disorder (OCD), however OCD-specific deficits have yet to be
      established. We investigated neural correlates of inhibition in OCD vs. healthy
      and anxious controls. METHODS: ERPs and reaction times (RTs) were compared
      between participants with OCD (n=20), panic disorder (PD; n=20) and healthy
      controls (HCs; n=20) during an adapted Go/NoGo task, which manipulated inhibitory
      difficulty. RESULTS: A classic P3 NoGo anteriorisation effect occurred across
      groups. Both clinical groups showed RT impairment, and similar topographical
      anomalies of several (P2, N2 and P3) ERP components. Notably, both clinical
      groups lacked the strong frontally maximal N2 component topography seen in the
      HCs, across stimuli. Additionally, with increasing inhibitory difficulty, N2
      latency increased in HCs but not in the clinical groups. CONCLUSIONS:
      Unexpectedly, ERP and behavioural anomalies during inhibition in OCD were not
      qualitatively different to those in PD, but were generally more severe. Common
      general and inhibitory deficits may underlie intrusive mental phenomena in both
      conditions. SIGNIFICANCE: This first ERP response inhibition study in OCD to
      include anxious controls disconfirmed hypotheses regarding OCD-specific
      inhibitory deficits, indicating the importance of comparing OCD to other
      conditions, to evaluate neurobiological models.

PMID- 24079949
TI  - Frontal hemodynamic changes precede EEG onset of temporal lobe seizures.
AB  - OBJECTIVE: A preictal state exists minutes or hours prior to the clinical
      seizure. We investigated whether hemodynamic changes preceding temporal lobe
      seizures were detectable in frontal scalp recordings using near-infrared
      spectroscopy (NIRS). Patients undergoing video-EEG telemetry (VET) were studied.
      METHODS: A NIRS sensor was placed over the frontal scalp ipsilateral to the
      patient's first recorded seizure. Regional cerebral oxygenation (rSO2) was
      recorded synchronously with VET data and peripheral oxygen saturation (SaO2).
      Periictal changes in rSO2 were compared with baseline interictal rSO2. RESULTS:
      Eleven seizures were recorded in six patients. A mean peak preictal increase in
      rSO2 of 7.1% from the interictal baseline (p<0.001) occurred at a mean peak
      latency of 298.9s before seizure onset. rSO2 then decreased around seizure onset.
      SaO2 nadir occurred at a mean latency of 62s following rSO2 nadir. A postictal
      increase in rSO2 occurred with a mean duration of about 35 min. Periictal rSO2
      changes occurred with both ipsi and contralateral temporal lobe seizures.
      CONCLUSION: We have shown that preictal changes in cerebral oxygenation occur
      with a mean peak latency of about 4.98 min before seizure onset. SIGNIFICANCE:
      NIRS has the potential for providing a noninvasively detected signal of an
      imminent seizure.

PMID- 24079950
TI  - Molecular detection of potential sexually transmitted pathogens in semen and
      urine specimens of infertile and fertile males.
AB  - A total of 93 infertile and 70 fertile men attending various urology and
      gynecology clinics in Jordan were investigated in this prospective study. First
      void urine and the corresponding semen specimens were collected from 96% of the
      patients. Presence of Neisseria gonorrhoeae (NG), Chlamydia trachomatis (CT),
      Ureaplasma urealyticum (UU), and Mycoplasma genitalium (MG) DNA in specimen was
      detected using polymerase chain reaction. The distribution of NG, CT, UU, and MG
      in semen and FVU specimens among infertile versus fertile men was 6.5% versus 0%,
      4.3% versus 1.4%, 10.8% versus 5.7%, and 3.2% versus 1.4%, respectively. Two of
      infertile and 1 of fertile men harbored mixed pathogens. The highest number of
      positive potential pathogens was found among young men aged 20-29 years old. The
      present study found a very high concordance between the detection of CT, UU, and
      MG DNA in semen and the corresponding FVU specimens, while NG DNA found only in
      semen and not in the corresponding FVU specimens. This study also revealed that
      Ureaplasma parvum species is more prevalent than Ureaplasma urealyticum in
      specimens of infertile men (90%). The study demonstrates that infertile men have
      higher prevalence of NG, CT, UU, and MG compared with fertile men and NG as
      significantly associated with infertile men. 

PMID- 24079951
TI  - Pooling ocular swab specimens from Tanzania for testing by Roche Amplicor and
      Aptima Combo 2 assays for the detection of Chlamydia trachomatis: accuracy and
      cost-savings.
AB  - Ocular swabs collected in Tanzania were evaluated by Amplicor CT PCR and Aptima
      Combo2 assays for the detection of Chlamydia trachomatis to determine if pooling
      could be used to reduce the cost of detection. Pooling would be an accurate
      method and has thus far resulted in a cost-savings of 62.2%. 

PMID- 24079952
TI  - Cost of temporary work disability due to musculoskeletal diseases in Spain.
AB  - OBJECTIVE: To estimate the annual cost of temporary work disability (TWD) caused
      by musculoskeletal diseases (MSDs) in Spain and its variations between regions
      (autonomous communities: ACs) and paying institutions. METHOD: Descriptive study
      of the costs of MSD-related TWD in ACs in 2007. The Spanish National Institute of
      Social Security (NISS) provided aggregate data. Extrapolations to the rest of the
      TWD payers (mutual societies and employers) were used. RESULTS: MSDs were the
      leading cause of TWD in Spain in 2007, causing 908,781 episodes of TWD (18% of
      the total), 39,342,857 lost working days (23%), and a cost of 1,702 million euros
      (23%). The annual incidence of TWD episodes per 1,000 employed was 45. The cost
      per TWD process was 1,873 ?, ranging from 1,391 ? (La Rioja) to 2,429 ? (Basque
      Country). CONCLUSION: MSDs produce annually in Spain over 39 million days lost by
      TWD with a cost of over 1,700 million euros. Regions observed wide variations of
      the TWD cost.

PMID- 24079953
TI  - Electronic structural Moire pattern effects on MoS2/MoSe2 2D heterostructures.
AB  - The structural and electronic properties of MoS2/MoSe2 bilayers are calculated
      using first-principles methods. It is found that the interlayer van der Waals
      interaction is not strong enough to form a lattice-matched coherent
      heterostructure. Instead, a nanometer-scale Moire pattern structure will be
      formed. By analyzing the electronic structures of different stacking
      configurations, we predict that the valence-band maximum (VBM) state will come
      from the Gamma point due to interlayer electronic coupling. This is confirmed by
      a direct calculation of a Moire pattern supercell containing 6630 atoms using the
      linear scaling three-dimensional fragment method. The VBM state is found to be
      strongly localized, while the conduction band minimum (CBM) state is only weakly
      localized, and it comes from the MoS2 layer at the K point. We predict such wave
      function localization can be a general feature for many two-dimensional (2D) van
      der Waals heterostructures and can have major impacts on the carrier mobility and
      other electronic and optical properties. 

PMID- 24079954
TI  - Determining the role of testosterone deficiency in sexual function: the beginning
      of the end or the end of the beginning?

PMID- 24079955
TI  - Robotic versus laparoscopic adrenalectomy: a systematic review and meta-analysis.
AB  - CONTEXT: Over the last decade, robot-assisted adrenalectomy has been included in
      the surgical armamentarium for the management of adrenal masses. OBJECTIVE: To
      critically analyze the available evidence of studies comparing laparoscopic and
      robotic adrenalectomy. EVIDENCE ACQUISITION: A systematic literature review was
      performed in August 2013 using PubMed, Scopus, and Web of Science electronic
      search engines. Article selection proceeded according to the search strategy
      based on Preferred Reporting Items for Systematic Reviews and Meta-analysis
      criteria. EVIDENCE SYNTHESIS: Nine studies were selected for the analysis
      including 600 patients who underwent minimally invasive adrenalectomy (277 robot
      assisted and 323 laparoscopic). Only one of the studies was a randomized clinical
      trial (RCT) but of low quality according to the Jadad scale. However, the
      methodological quality of included nonrandomized studies was relatively high.
      Body mass index was higher for the laparoscopic group (weighted mean difference
      [WMD]: -2.37; 95% confidence interval [CI], - 3.01 to -1.74; p<0.00001). A
      transperitoneal approach was mostly used for both techniques (72.5% of robotic
      cases and 75.5% of laparoscopic cases; p=0.27). There was no significant
      difference between the two groups in terms of conversion rate (odds ratio [OR]:
      0.82; 95% CI, 0.39-1.75; p=0.61) and operative time (WMD: 5.88; 95% CI, -6.02 to
      17.79; p=0.33). There was a significantly longer hospital stay in the
      conventional laparoscopic group (WMD: -0.43; 95% CI, -0.56 to -0.30; p<0.00001),
      as well as a higher estimated blood loss (WMD: -18.21; 95% CI, -29.11 to -7.32;
      p=0.001). There was also no statistically significant difference in terms of
      postoperative complication rate (OR: 0.04; 95% CI, -0.07 to -0.00; p=0.05)
      between groups. Most of the postoperative complications were minor (80% for the
      robotic group and 68% for the conventional laparoscopic group). Limitations of
      the present analysis are the limited sample size and including only one low
      quality RCT. CONCLUSIONS: Robot-assisted adrenalectomy can be performed safely
      and effectively with operative time and conversion rates similar to laparoscopic
      adrenalectomy. In addition, it can provide potential advantages of a shorter
      hospital stay, less blood loss, and lower occurrence of postoperative
      complications. These findings seem to support the use of robotics for the
      minimally invasive surgical management of adrenal masses.

PMID- 24079956
TI  - Diagnostic pitfalls in the preoperative 18F-FDG PET/CT evaluation of a case of
      giant malignant solitary fibrous tumor of the pleura.
AB  - Solitary fibrous tumor of the pleura (SFTP) is an uncommon entity, generally with
      an indolent behavior. Nevertheless, some malignant forms have been rarely
      reported. These, often have an aggressive biological behavior with pathological
      findings of invasiveness. The preoperative diagnosis and evaluation of the grade
      of malignancy are extremely challenging. Herein we report a case of a 64-year-old
      man who presented with a left giant intra-thoracic mass imaged with fluorine-18
      fluorodeoxyglucose positron emission tomography/computed tomography ((18)F
      FDG/PET-CT) and sampled via fine-needle aspiration biopsy (FNAB). Imaging and
      FNAB findings showed suspicion of a benign form of SFTP. Surgical radical
      resection of the giant mass was performed. The definitive histological diagnosis
      showed a malignant SFTP. Based on this report, we take the opportunity to briefly
      discuss the insidious pitfalls concerning the radiological and (18)F-FDG/PET-CT
      features as well as cyto/histological findings in the pre-operative diagnostic
      work-up examination of this rare entity. 

PMID- 24079957
TI  - Callous-unemotional traits in incarcerated adolescents.
AB  - The presence of callous-unemotional (CU) traits designates a subgroup of
      antisocial youth at risk for severe, aggressive, and stable conduct problems. As
      a result, these traits should be considered as part of the criteria for conduct
      disorder. The present study tests 2 possible symptom sets (4- and 9-item criteria
      sets) of CU traits that could be used in diagnostic classification, assessed
      using self-report with a sample of 643 incarcerated adolescent (M age = 16.50, SD
      = 1.63 years) boys (n = 493) and girls (n = 150). Item response theory analysis
      was employed to examine the unique characteristics of each criterion comprising
      the 2 sets to determine their clinical utility. Results indicated that most items
      comprising the measure of CU traits demonstrated adequate psychometric
      properties. Whereas the 9-item criteria set provided more information and was
      internally consistent, the briefer 4-item set was equally effective at
      identifying youth at-risk for poor outcomes associated with the broader CU
      construct. Supporting the clinical utility of the criteria sets, incarcerated
      boys and girls who endorsed high levels of CU symptoms across criteria sets were
      particularly at-risk for proactive aggression and violent delinquency.

PMID- 24079958
TI  - Factorial validity and measurement invariance across intelligence levels and
      gender of the overexcitabilities questionnaire-II (OEQ-II).
AB  - The concept of overexcitability, derived from Dabrowski's theory of personality
      development, offers a promising approach for the study of the developmental
      dynamics of giftedness. The present study aimed at (a) examining the factorial
      structure of the Overexcitabilities Questionnaire-II scores (OEQ-II) and (b)
      testing measurement invariance of these scores across intelligence and gender. A
      sample of 641 Dutch-speaking adolescents from 11 to 15 years old, 363 girls and
      278 boys, participated in this study. Results showed that a model without cross
      loadings did not fit the data well (using confirmatory factor analysis), whereas
      a factor model in which all cross-loadings were included yielded fit statistics
      that were in support of the factorial structure of the OEQ-II scores (using
      exploratory structural equation modeling). Furthermore, our findings supported
      the assumption of (partial) strict measurement invariance of the OEQ-II scores
      across intelligence levels and across gender. Such levels of measurement
      invariance allow valid comparisons between factor means and factor relationships
      across groups. In particular, the gifted group scored significantly higher on
      intellectual and sensual overexcitability (OE) than the nongifted group, girls
      scored higher on emotional and sensual OE than boys, and boys scored higher on
      intellectual and psychomotor OE than girls.

PMID- 24079959
TI  - Examining intimate partner aggression assessment among returning veterans and
      their partners.
AB  - There is a growing research base focusing on intimate partner aggression (IPA) in
      combat veterans, although little work has focused on IPA assessment. In the
      current study, the authors investigated IPA assessment among 65 male Operation
      Iraqi Freedom (OIF) and Operation Enduring Freedom (OEF) combat veterans and
      their female partners. Specifically, we compared overall levels of veteran- and
      partner-perpetrated IPA, conducted concordance analyses to examine the degree of
      interpartner agreement on IPA occurrence and frequency, and investigated both
      veterans' and partners' relationship satisfaction and posttraumatic stress
      disorder (PTSD) symptoms as correlates of concordance. Results indicated that
      female partners perpetrated higher levels of physical IPA than did the male
      veterans, according to both veteran and combined reports. Concordance analyses
      revealed low to moderate levels of agreement between veterans and their partners
      on the perpetration of physical and psychological IPA, with particularly low
      agreement on the veterans' physical IPA. Female partners' relationship
      satisfaction was associated with reporting less of the veterans' and their own
      IPA relative to the veterans' reports, and their PTSD symptoms were associated
      with reporting more of the veterans' and their own IPA. In contrast, the
      veterans' PTSD symptoms were associated with reporting less of their own IPA
      relative to their partners' reports. The findings emphasize the need for those
      researching and treating IPA among military couples to assess IPA perpetrated by
      both members of the relationship and to consider possible factors that might
      impact the accuracy of IPA reporting.

PMID- 24079960
TI  - Single-port versus conventional multiport laparoscopic cholecystectomy: a meta
      analysis of randomized controlled trials and nonrandomized studies.
AB  - BACKGROUND: Although current guidelines recommend performing cholecystectomy via
      laparoscopy, consensus on the application of single-incision laparoscopic surgery
      for cholecystectomy is still lacking. The aim of the current study was to perform
      a meta-analysis of randomized controlled trials (RCTs) and nonrandomized
      comparative studies (NRCSs), comparing single-port laparoscopic cholecystectomy
      (SPLC) and conventional multiport laparoscopic cholecystectomy (CMLC) for benign
      gallbladder diseases. SUBJECTS AND METHODS: A systematic review of the literature
      was performed to identify studies published between January 1997 and December
      2012 comparing SPLC and CMLC. Operative outcomes, postoperative parameters,
      complications, cosmetic results, and quality of life were evaluated. RESULTS:
      Forty studies were included in the analyses (16 RCTs, 24 NRCSs) that included
      3711 patients (1865 SPLCs, 1846 CMLCs). SPLC had higher conversion rates (odds
      ratio [OR], 4.21; 95% confidence interval [CI], 2.71-6.56; P<.001), longer
      operating time (mean difference [MD], 16.1; 95% CI, 9.93-22.26 minutes; P<.001),
      and shorter hospital stay (MD, 0.16; 95% CI, -0.28 to -0.04 day; P=.01) than
      CMLC. There were no significant differences between the two procedures for early
      (MD, -0.1; 95% CI, -0.44 to 0.24; P=.57) or late (MD, -0.13; 95% CI, -0.45 to
      0.19; P=.42) visual analog scale pain scores and overall complications (OR, 1.21;
      95% CI, 0.92-1.61; P=.18). Cosmetic outcomes favored SILC at 2 weeks (MD, -1.39;
      95% CI, -2.66 to -0.12; P=.03) and 1 month (MD, -0.13, 95% CI, -2.05 to 0.55;
      P=.0007) after surgery (index score, 0-10). CONCLUSIONS: SPLC can be performed
      safely and effectively with better cosmetic results than with the CMLC technique
      for benign gallbladder diseases.

PMID- 24079961
TI  - Laparoscopic versus open treatment of congenital duodenal obstruction:
      multicenter short-term outcomes analysis.
AB  - BACKGROUND: Laparoscopic repair of congenital duodenal obstruction has become
      popularized over the past decade. Comparative data on outcomes, however, are
      sparse. We hypothesized that laparoscopic repair of congenital duodenal
      obstruction could be performed with similar outcomes to traditional open repair.
      PATIENTS AND METHODS: Medical records for all cases of congenital duodenal
      obstruction from 2005 to 2011 at three academic teaching hospitals were
      retrospectively reviewed. Patients were excluded from the analysis if they had
      confounding surgical diseases, did not have duodenoduodenostomy during the first
      hospital admission, had the repair performed before transfer from a referring
      hospital, or weighed less than 1.7  kg at the time of surgery. Analysis was
      performed as intention to treat, with laparoscopic converted to open cases
      included in the laparoscopic group. RESULTS: Sixty-four cases were included in
      the analysis (44 open, 20 laparoscopic). Baseline characteristics were similar
      between the two groups with the exception that the open group, on average,
      underwent repair later than the laparoscopic group (6 days versus 4 days,
      respectively). Seven laparoscopic cases were converted to an open procedure
      (35%), most commonly for difficulty in exposing the decompressed distal duodenum.
      Laparoscopic repair did take significantly longer than open repair (145 minutes
      versus 96 minutes, respectively), but clinical outcomes were similar.
      Complications were rare and were similar between methods of repair. Two patients
      in the laparoscopic group required subsequent open revision. CONCLUSIONS:
      Laparoscopic duodenoduodenostomy for congenital duodenal obstruction is a
      technically challenging procedure with a steep learning curve. Despite a
      relatively high conversion rate, clinical outcomes remained similar to the
      traditional open repair in selected patients.

PMID- 24079962
TI  - Antimicrobial functions on cellulose materials introduced by anthraquinone vat
      dyes.
AB  - Many anthraquinone compounds have exhibited light-active properties in solutions
      and on materials under UVA or fluorescent light exposure. Two anthraquinone
      derivatives were incorporated onto cotton fabrics by a vat dyeing process. The
      dyed fabrics demonstrated light-induced biocidal functions, and the functions
      were durable against laundering and long-term light exposure. The structures and
      surface morphologies of the dyed fabrics were examined by using fourier transform
      infrared (FTIR) spectroscopy and scanning electron microscopy (SEM). Mechanical
      properties of the fabrics were measured by using a tensile tester. The results
      revealed that the anthraquinone compounds have different light-activities,
      resulting in different surface and mechanical impacts on the cotton cellulose. 

PMID- 24079963
TI  - Triboelectric nanogenerators as new energy technology for self-powered systems
      and as active mechanical and chemical sensors.
AB  - Triboelectrification is an effect that is known to each and every one probably
      since ancient Greek time, but it is usually taken as a negative effect and is
      avoided in many technologies. We have recently invented a triboelectric
      nanogenerator (TENG) that is used to convert mechanical energy into electricity
      by a conjunction of triboelectrification and electrostatic induction. As for this
      power generation unit, in the inner circuit, a potential is created by the
      triboelectric effect due to the charge transfer between two thin
      organic/inorganic films that exhibit opposite tribo-polarity; in the outer
      circuit, electrons are driven to flow between two electrodes attached on the back
      sides of the films in order to balance the potential. Since the most useful
      materials for TENG are organic, it is also named organic nanogenerator, which is
      the first using organic materials for harvesting mechanical energy. In this
      paper, we review the fundamentals of the TENG in the three basic operation modes:
      vertical contact-separation mode, in-plane sliding mode, and single-electrode
      mode. Ever since the first report of the TENG in January 2012, the output power
      density of TENG has been improved 5 orders of magnitude within 12 months. The
      area power density reaches 313 W/m(2), volume density reaches 490 kW/m(3), and a
      conversion efficiency of ~60% has been demonstrated. The TENG can be applied to
      harvest all kinds of mechanical energy that is available but wasted in our daily
      life, such as human motion, walking, vibration, mechanical triggering, rotating
      tire, wind, flowing water, and more. Alternatively, TENG can also be used as a
      self-powered sensor for actively detecting the static and dynamic processes
      arising from mechanical agitation using the voltage and current output signals of
      the TENG, respectively, with potential applications for touch pad and smart skin
      technologies. To enhance the performance of the TENG, besides the vast choices of
      materials in the triboelectric series, from polymer to metal and to fabric, the
      morphologies of their surfaces can be modified by physical techniques with the
      creation of pyramid-, square-, or hemisphere-based micro- or nanopatterns, which
      are effective for enhancing the contact area and possibly the
      triboelectrification. The surfaces of the materials can be functionalized
      chemically using various molecules, nanotubes, nanowires, or nanoparticles, in
      order to enhance the triboelectric effect. The contact materials can be
      composites, such as embedding nanoparticles in a polymer matrix, which may change
      not only the surface electrification but also the permittivity of the materials
      so that they can be effective for electrostatic induction. Therefore, there are
      numerous ways to enhance the performance of the TENG from the materials point of
      view. This gives an excellent opportunity for chemists and materials scientists
      to do extensive study both in the basic science and in practical applications. We
      anticipate that a better enhancement of the output power density will be achieved
      in the next few years. The TENG is possible not only for self-powered portable
      electronics but also as a new energy technology with potential to contribute to
      the world energy in the near future. 

PMID- 24079964
TI  - A new measure for gene expression biclustering based on non-parametric
      correlation.
AB  - BACKGROUND: One of the emerging techniques for performing the analysis of the DNA
      microarray data known as biclustering is the search of subsets of genes and
      conditions which are coherently expressed. These subgroups provide clues about
      the main biological processes. Until now, different approaches to this problem
      have been proposed. Most of them use the mean squared residue as quality measure
      but relevant and interesting patterns can not be detected such as shifting, or
      scaling patterns. Furthermore, recent papers show that there exist new coherence
      patterns involved in different kinds of cancer and tumors such as inverse
      relationships between genes which can not be captured. RESULTS: The proposed
      measure is called Spearman's biclustering measure (SBM) which performs an
      estimation of the quality of a bicluster based on the non-linear correlation
      among genes and conditions simultaneously. The search of biclusters is performed
      by using a evolutionary technique called estimation of distribution algorithms
      which uses the SBM measure as fitness function. This approach has been examined
      from different points of view by using artificial and real microarrays. The
      assessment process has involved the use of quality indexes, a set of bicluster
      patterns of reference including new patterns and a set of statistical tests. It
      has been also examined the performance using real microarrays and comparing to
      different algorithmic approaches such as Bimax, CC, OPSM, Plaid and xMotifs.
      CONCLUSIONS: SBM shows several advantages such as the ability to recognize more
      complex coherence patterns such as shifting, scaling and inversion and the
      capability to selectively marginalize genes and conditions depending on the
      statistical significance.

PMID- 24079965
TI  - A preliminary study on the use of clinical care classification in nursing
      documentation data sets.
AB  - This study analyzed and organized the content coverage of the clinical care
      classification (CCC) system to represent nursing record data in a medical center
      in Taiwan. The nursing care plan was analyzed using the process of knowledge
      discovery in the data set. The nursing documentation was mapped based on the full
      list of nursing diagnoses and interventions available using the CCC system. The
      result showed that 75.45% of the documented diagnosis terms can be mapped using
      the CCC system. A total of 21 established nursing diagnoses were recommended for
      inclusion in the CCC system. The results also showed that 30.72% of
      assessment/monitor tasks and 31.16% of care/perform tasks were provided by
      nursing professionals, whereas manage/refer actions accounted for 15.36% of the
      tasks involved in nursing care. The results showed that the CCC system is a
      suitable clinical information system for the majority of nursing care
      documentation, and is useful for determining the patterns in nursing practices. 

PMID- 24079966
TI  - A photoelectrocatalytic process that disinfects water contaminated with
      Mycobacterium kansasii and Mycobacterium avium.
AB  - Nontuberculous mycobacteria are resistant to conventional water treatment;
      indeed, they have been recovered from a wide variety of environmental sources.
      Here, we applied the photoelectrocatalytic technique using a Ti/TiO2-Ag
      photoanode to inactivate mycobacteria. For a mycobacteria population of 5 * 10(8)
      CFU mL(-1), we achieved 99.9 and 99.8% inactivation of Mycobacterium kansasii and
      Mycobacterium avium with rate constant of 6.2 * 10(-3) and 4.2 * 10(-3) min(-1),
      respectively, after 240 min. We compared the proposed method with the photolytic
      and photocatalytic methods. Using a mycobacteria population of 7.5 * 10(4) CFU
      mL(-1), the proposed Ti/TiO2-Ag photoanode elicited total mycobacteria
      inactivation within 3 min of treatment; the presence of Ag nanoparticles in the
      electrode provided 1.5 larger degradation rate constant as compared with the
      Ti/TiO2 anode (1.75 * 10(-2) for M. kansassi and 1.98 * 10(-2) for M. avium). We
      monitored the degradation of the metabolites released during cellular lysis by
      TOC removal, sugar release, chromatography, and mass spectrometry measurements;
      photoelectrocatalysis and Ti/TiO2-Ag photoanodes furnished the best results.

PMID- 24079967
TI  - Impact of ZnO embedded feed spacer on biofilm development in membrane systems.
AB  - The concept of suppressing biofouling formation using an antibacterial feed
      spacer was investigated in a bench scale-cross flow system mimicking a spiral
      wound membrane configuration. An antibacterial composite spacer containing zinc
      oxide-nanoparticles was constructed by modification of a commercial polypropylene
      feed spacer using sonochemical deposition. The ability of the modified spacers to
      repress biofilm development on membranes was evaluated in flow-through cells
      simulating the flow conditions in commercial spiral wound modules. The
      experiments were performed at laminar flow (Re = 300) with a 200 kDa molecular
      weight cut off polysulfone ultrafiltration membrane using Pseudomonas putida S-12
      as model biofilm bacteria. The modified spacers reduced permeate flux decrease at
      least by 50% compared to the unmodified spacers (control). The physical
      properties of the modified spacer and biofilm development were evaluated using
      high resolution/energy dispersive spectrometry-scanning electron microscopy,
      atomic force microscopy and confocal laser scanning microscopy imaging (HRSEM,
      EDS, AFM and CLSM). HRSEM images depicted significantly less bacteria attached to
      the membranes exposed to the modified spacer, mainly scattered and in a sporadic
      monolayer structure. AFM analysis indicated the influence of the modification on
      the spacer surface including a phase change on the upper surface. Dead-live
      staining assay by CLSM indicated that most of the bacterial cells attached on the
      membranes exposed to the modified spacer were dead in contrast to a developed
      biofilm which was predominant in the control samples.

PMID- 24079968
TI  - Using SWAT, Bacteroidales microbial source tracking markers, and fecal indicator
      bacteria to predict waterborne pathogen occurrence in an agricultural watershed.
AB  - Developing the capability to predict pathogens in surface water is important for
      reducing the risk that such organisms pose to human health. In this study, three
      primary data source scenarios (measured stream flow and water quality, modelled
      stream flow and water quality, and host-associated Bacteroidales) are
      investigated within a Classification and Regression Tree Analysis (CART)
      framework for classifying pathogen (Escherichia coli 0157:H7, Salmonella,
      Campylobacter, Cryptosporidium, and Giardia) presence and absence (P/A) for a 178
      km(2) agricultural watershed. To provide modelled data, a Soil Water Assessment
      Tool (SWAT) model was developed to predict stream flow, total suspended solids
      (TSS), total N and total P, and fecal indicator bacteria loads; however, the
      model was only successful for flow and total N and total P simulations, and did
      not accurately simulate TSS and indicator bacteria transport. Also, the SWAT
      model was not sensitive to an observed reduction in the cattle population within
      the watershed that may have resulted in significant reduction in E. coli
      concentrations and Salmonella detections. Results show that when combined with
      air temperature and precipitation, SWAT modelled stream flow and total P
      concentrations were useful for classifying pathogen P/A using CART methodology.
      From a suite of host-associated Bacteroidales markers used as independent
      variables in CART analysis, the ruminant marker was found to be the best initial
      classifier of pathogen P/A. Of the measured sources of independent variables, air
      temperature, precipitation, stream flow, and total P were found to be the most
      important variables for classifying pathogen P/A. Results indicate a close
      relationship between cattle pollution and pathogen occurrence in this watershed,
      and an especially strong link between the cattle population and Salmonella
      detections.

PMID- 24079969
TI  - Intracellular Ca(2+) remodeling during the phenotypic journey of human coronary
      smooth muscle cells.
AB  - Vascular smooth muscle cells undergo phenotypic switches after damage which may
      contribute to proliferative disorders of the vessel wall. This process has been
      related to remodeling of Ca(2+) channels. We have tested the ability of cultured
      human coronary artery smooth muscle cells (hCASMCs) to return from a
      proliferative to a quiescent behavior and the contribution of intracellular
      Ca(2+) remodeling to the process. We found that cultured, early passage hCASMCs
      showed a high proliferation rate, sustained increases in cytosolic [Ca(2+)] in
      response to angiotensin II, residual voltage-operated Ca(2+) entry, increased
      Stim1 and enhanced store-operated currents. Non-steroidal anti-inflammatory drugs
      inhibited store-operated Ca(2+) entry and abolished cell proliferation in a
      mitochondria-dependent manner. After a few passages, hCASMCs turned to a
      quiescent phenotype characterized by lack of proliferation, oscillatory Ca(2+)
      response to angiotensin II, increased Ca(2+) store content, enhanced voltage
      operated Ca(2+) entry and Cav1.2 expression, and decreases in Stim1, store
      operated current and store-operated Ca(2+) entry. We conclude that proliferating
      hCASMCs return to quiescence and this switch is associated to a remodeling of
      Ca(2+) channels and their control by subcellular organelles, thus providing a
      window of opportunity for targeting phenotype-specific Ca(2+) channels involved
      in proliferation. 

PMID- 24079970
TI  - Mechanisms for L-channel-mediated increase in [Ca(2+)]i and its reduction by anti
      bipolar drugs in cultured astrocytes combined with its mRNA expression in freshly
      isolated cells support the importance of astrocytic L-channels.
AB  - The importance of Ca(2+) signaling in astrocytes is undisputed but a potential
      role of Ca(2+) influx via L-channels in the brain in vivo is disputed, although
      expression of these channels in cultured astrocytes is recognized. This study
      shows that an increase in free cytosolic Ca(2+) concentration ([Ca(2+)]i) in
      astrocytes in primary cultures in response to an increased extracellular K(+)
      concentration (45mM) is inhibited not only by nifedipine (confirming previous
      observations) but also to a very large extent by ryanodine, inhibiting ryanodine
      receptor-mediated release of Ca(2+), known to occur in response to an elevation
      in [Ca(2+)]i. This means that the actual influx of Ca(2+) is modest, which may
      contribute to the difficulty in demonstrating L-channel-mediated Ca(2+) currents
      in astrocytes in intact brain tissue. Chronic treatment with any of the 3
      conventional anti-bipolar drugs lithium, carbamazepine or valproic acid similarly
      causes a pronounced inhibition of K(+)-mediated increase in [Ca(2+)]i. This is
      shown to be due to an inhibition of capacitative Ca(2+) influx, reflected by
      decreased mRNA and protein expression of the 'transient receptor potential
      channel' (TRPC1), a constituent of store-operated channels (SOCEs). Literature
      data are cited (i) showing that depolarization-mediated Ca(2+) influx in response
      to an elevated extracellular K(+) concentration is important for generation of
      Ca(2+) oscillations and for the stimulatory effect of elevated K(+)
      concentrations in intact, non-cultured brain tissue, and (ii) that Ca(2+) channel
      activity is dependent upon availability of metabolic substrates, including
      glycogen. Finally, expression of mRNA for Cav1.3 is demonstrated in freshly
      separated astrocytes from normal brain. 

PMID- 24079971
TI  - Lack of correlation between the amplitudes of TRP channel-mediated responses to
      weak and strong stimuli in intracellular Ca(2+) imaging experiments.
AB  - It is often observed in intracellular Ca(2+) imaging experiments that the
      amplitudes of the Ca(2+) signals elicited by newly characterized TRP agonists do
      not correlate with the amplitudes of the responses evoked subsequently by a
      specific potent agonist. We investigated this rather controversial phenomenon by
      first testing whether it is inherent to the comparison of the effects of weak and
      strong stimuli. Using five well-characterized TRP channel agonists in commonly
      used heterologous expression systems we found that the correlation between the
      amplitudes of the Ca(2+) signals triggered by two sequentially applied stimuli is
      only high when both stimuli are strong. Using mathematical simulations of
      intracellular Ca(2+) dynamics we illustrate that the innate heterogeneity in
      expression and functional properties of Ca(2+) extrusion (e.g. plasma membrane
      Ca(2+) ATPase) and influx (TRP channels) pathways across a cellular population is
      a sufficient condition for low correlation between the amplitude of Ca(2+)
      signals elicited by weak and strong stimuli. Taken together, our data demonstrate
      that this phenomenon is an expected outcome of intracellular Ca(2+) imaging
      experiments that cannot be taken as evidence for lack of specificity of low
      efficacy stimuli, or as an indicator of the need of other cellular components for
      channel stimulation. 

PMID- 24079973
TI  - Deposition of metal nanoparticles on phospholipid multilayer membranes modified
      by gramicidin.
AB  - A planar dipalmitoyl phosphatidylcholine (DPPC) multilayer phospholipid membrane
      was structurally modified by introducing a transmembrane protein, gramicidin (up
      to 25 mol %), to study its effect on the metal nanoparticles deposited on the
      membrane. Without gramicidin, when 3-nm-thick Ag, Sn, Al, and Au were deposited,
      the nanoparticles hardly nucleated on the DPPC membrane in rigid gel state
      (except for Au); however, the gramicidin addition dramatically enhanced the DPPC
      membrane surface's affinity for metal atoms so that a dense array of metal (Ag,
      Sn, and Au) or metal-oxide (Al-oxide) nanoparticles was produced on the membrane
      surface. The particle sizes ranged from 3 to 15 nm depending on the metal and
      gramicidin concentration, whereas the particle density was strongly dictated by
      the gramicidin concentration. The proposed method provides a convenient,
      generally applicable synthesis route for preparing different metal or metal-oxide
      nanoparticles on a relatively robust biocompatible membrane. 

PMID- 24079972
TI  - Constitutive expression of selected genes from the pentose phosphate and aromatic
      pathways increases the shikimic acid yield in high-glucose batch cultures of an
      Escherichia coli strain lacking PTS and pykF.
AB  - BACKGROUND: During the last two decades many efforts have been directed towards
      obtaining efficient microbial processes for the production of shikimic acid (SA);
      however, feeding high amounts of substrate to increase the titer of this compound
      has invariably rendered low conversion yields, leaving room for improvement of
      the producing strains. In this work we report an alternative platform to
      overproduce SA in a laboratory-evolved Escherichia coli strain, based on plasmid
      driven constitutive expression of six genes selected from the pentose phosphate
      and aromatic amino acid pathways, artificially arranged as an operon. Production
      strains also carried inactivated genes coding for phosphotransferase system
      components (ptsHIcrr), shikimate kinases I and II (aroK and aroL), pyruvate
      kinase I (pykF) and the lactose operon repressor (lacI). RESULTS: The strong and
      constitutive expression of the constructed operon permitted SA production from
      the beginning of the cultures, as evidenced in 1 L batch-mode fermentors starting
      with high concentrations of glucose and yeast extract. Inactivation of the pykF
      gene improved SA production under the evaluated conditions by increasing the
      titer, yield and productivity of this metabolite compared to the isogenic pykF+
      strain. The best producing strain accumulated up to 43 g/L of SA in 30 h and
      relatively low concentrations of acetate and aromatic byproducts were detected,
      with SA accounting for 80% of the produced aromatic compounds. These results were
      consistent with high expression levels of the glycolytic pathway and synthetic
      operon genes from the beginning of fermentations, as revealed by transcriptomic
      analysis. Despite the consumption of 100 g/L of glucose, the yields on glucose of
      SA and of total aromatic compounds were about 50% and 60% of the theoretical
      maximum, respectively. The obtained yields and specific production and
      consumption rates proved to be constant with three different substrate
      concentrations. CONCLUSIONS: The developed production system allowed continuous
      SA accumulation until glucose exhaustion and eliminated the requirement for
      culture inducers. The obtained SA titers and yields represent the highest
      reported values for a high-substrate batch process, postulating the strategy
      described in this report as an interesting alternative to the traditionally
      employed fed-batch processes for SA production.

PMID- 24079974
TI  - Time to task failure influences the postural alteration more than the extent of
      muscles fatigued.
AB  - The aim of this study was to compare the effects of unilateral and bilateral
      muscle fatigue on monopedal postural control. Nineteen subjects completed
      bilateral fatiguing contractions and unilateral fatiguing contractions of the
      quadriceps femoris until the torque output for both exercises dropped below 30%
      of the measured peak torque (the time to task failure was measured) for three
      consecutive contractions (independently measured for each leg). Postural control
      was evaluated by using a force platform which recorded center of foot pressure
      (COP) and was measured before and after the completion of both fatiguing tasks.
      Spatio-temporal COP parameters were used to evaluate postural control. The
      unilateral contractions affected monopedal postural control more than the
      bilateral fatiguing contractions (p<0.05). Moreover, the time to task failure was
      significantly longer for the unilateral contractions than for the bilateral
      contractions (p<0.05). The greater alteration of postural control for the
      unilateral fatiguing contractions compared to the bilateral fatiguing
      contractions could be related to a longer time to task failure which could
      provoke greater disturbances of the postural system in terms of sensory input and
      motor output. 

PMID- 24079975
TI  - Repeatability and validation of gait deviation index in children: typically
      developing and cerebral palsy.
AB  - The Gait Deviation Index (GDI) is a dimensionless parameter that evaluates the
      deviation of kinematic gait from a control database. The GDI can be used to
      stratify gait pathology in children with cerebral palsy (CP). In this paper the
      repeatability and uncertainty of the GDI were evaluated. The Correlation between
      the GDI and the Gross Motor Function Classification System (GMFCS) was studied
      for different groups of children with CP (hemiplegia, diplegia, triplegia and
      quadriplegia). Forty-nine, typically developing children (TD) formed our
      database. A retrospective study was conducted on our 3D gait data and clinical
      exams and 134 spastic children were included. Sixteen TD children completed the
      gait analysis twice to evaluate the repeatability of the GDI (test-retest
      evaluation). Monte Carlo simulations were applied for all groups (TD and children
      with CP) in order to evaluate the propagation of errors stemming from kinematics.
      The repeatability coefficient (2SD of test-retest differences), obtained on the
      GDI for the 16 TD children (32 lower limbs) was +/- 10. Monte Carlo simulations
      showed an uncertainty ranging between 0.8 and 1.3 for TD children and all groups
      with CP. The Spearman Rank correlation showed a moderate correlation between the
      GDI and the GMFCS (r=-0.44, p<0.0001).

PMID- 24079977
TI  - Robot-assisted laparoscopic excision of a retroperitoneal paracaval tumor.
AB  - During the past few years, robotic surgical systems have been rapidly developed.
      The progress and advantages of these systems include three-dimensional vision and
      enhanced ergonomics. These advantages have helped a new generation of minimally
      invasive surgery to evolve. The da Vinci Surgical System seems to greatly resolve
      problems (e.g., wide exposure and retraction of peritoneal organs) that are
      confronted by traditional laparoscopic surgeries for retroperitoneal tumors that
      are near great vessels. There have been few reported cases concerning
      laparoscopic excision of retroperitoneal tumors situated between the inferior
      vena cava, the right renal vessel, and the kidney. We report the use of a robotic
      surgical system for this type of treatment. A 54-year-old female patient had a
      hypoechoic lesion near the inferior vena cava and superior to the right renal
      vessels. It was incidentally found by ultrasound during a health check-up
      examination. The computed tomography (CT) scan revealed a heterogeneous contrast
      enhanced retroperitoneal mass approximately 4.4 cm medial to the right kidney
      with the inferior vena cava slightly deviated to the left. Robot-assisted
      laparoscopic excision of the retroperitoneal tumor was performed on October 15,
      2010 with an operation time of 135 minutes and an estimated blood loss of less
      than 30 mL. The J-Vac drainage tube was removed on postoperative Day 3, and the
      patient was discharged in a stable condition the following day. The pathology of
      the tumor was retroperitoneal schwannoma. A re-evaluation was arranged
      postoperatively for the 15-month ambulatory visit. No local recurrence or distal
      metastasis was present.

PMID- 24079978
TI  - High-pressure synthesis, crystal structures, and properties of ScRhO3 and InRhO3
      perovskites.
AB  - ScRhO3 and InRhO3 perovskites were synthesized at a high pressure of 6 GPa and a
      high temperature of 1500 K. Crystal structures of ScRhO3 and InRhO3 were studied
      with synchrotron X-ray powder diffraction at 293 and 134 K. ScRhO3 and InRhO3
      have a rarely observed monoclinic superstructure of the GdFeO3-type structure
      (space group P21/n, a = 7.45660 A, b = 7.43524 A, c = 7.52191 A, and beta =
      93.2930 degrees  for ScRhO3 and a = 7.59020 A, b = 7.58377 A, c = 7.59010 A, and
      beta = 91.4154 degrees  for InRhO3 at 293 K). InRhO3 has pseudo-orthorhombic
      lattice parameters of a = 10.8658 A, b = 7.5837 A, and c = 10.6006 A. ScRhO3 and
      InRhO3 are nonmagnetic, and no phase transitions were detected between 2 and 873
      K. Crystallographic trends and distortions of ScRhO3, InRhO3, and RRhO3 (R = rare
      earths, Y, and Bi) are discussed. 

PMID- 24079976
TI  - Streptococcal co-infection augments Candida pathogenicity by amplifying the
      mucosal inflammatory response.
AB  - Mitis-group streptococci are ubiquitous oral commensals that can promote
      polybacterial biofilm virulence. Using a novel murine oral mucosal co-infection
      model we sought to determine for the first time whether these organisms promote
      the virulence of C. albicans mucosal biofilms in oropharyngeal infection and
      explored mechanisms of pathogenic synergy. We found that Streptococcus oralis
      colonization of the oral and gastrointestinal tract was augmented in the presence
      of C. albicans. S. oralis and C. albicans co-infection significantly augmented
      the frequency and size of oral thrush lesions. Importantly, S. oralis promoted
      deep organ dissemination of C. albicans. Whole mouse genome tongue microarray
      analysis showed that when compared with animals infected with one organism, the
      doubly infected animals had genes in the major categories of neutrophilic
      response/chemotaxis/inflammation significantly upregulated, indicative of an
      exaggerated inflammatory response. This response was dependent on TLR2 signalling
      since oral lesions, transcription of pro-inflammatory genes and neutrophil
      infiltration, were attenuated in TLR2(-/-) animals. Furthermore, S. oralis
      activated neutrophils in a TLR2-dependent manner in vitro. In summary, this study
      identifies a previously unrecognized pathogenic synergy between oral commensal
      bacteriaand C. albicans. This is the first report of the ability of mucosal
      commensal bacteria to modify the virulence of an opportunistic fungal pathogen.

PMID- 24079979
TI  - Risk of yellow fever vaccine-associated viscerotropic disease among the elderly:
      a systematic review.
AB  - Yellow fever vaccine-associated viscerotropic disease (YEL-AVD) is a rare and
      serious adverse event of the yellow fever (YF) vaccine that mimics wild-type YF.
      Research shows there may be an increased risk of YEL-AVD among the elderly
      population (>= 60-65 years old), however this research has yet to be accumulated
      and reviewed in order to make policy recommendations to countries currently
      administering the YF vaccine. This paper systematically reviewed all information
      available on YEL-AVD to determine if there is an increased risk among the
      elderly, for both travelers and endemic populations. Age-specific reporting rates
      (RRs) were re-calculated from the literature using the Brighton Collaboration
      case definition for YEL-AVD and were then analyzed to determine if there was a
      significant difference between the RRs of younger and older age groups. Two out
      of the five studies found a significantly higher rate of YEL-AVD among the
      elderly population. Our findings suggest unexposed elders may be at an increased
      risk of developing YEF-AVD, however the evidence remains limited. Therefore, our
      findings for YF vaccination of elderly populations support the recommendations
      made by the Strategic Advisory Group of Experts (SAGE) in their April 2013
      meeting, mainly vaccination of the elderly should be based on a careful risk
      benefit analysis.

PMID- 24079980
TI  - New aminocoumarin antibiotics as gyrase inhibitors.
AB  - The aminocoumarins novobiocin, clorobiocin and coumermycin A1 are structurally
      related antibiotics produced by different Streptomyces strains. They are potent
      inhibitors of bacterial gyrase. Their binding sites and their mode of action
      differ from those of fluoroquinolones such as ciprofloxacin. Novobiocin has been
      introduced into clinical use against Staphylococcus aureus infections, and S.
      aureus gyrase is particularly sensitive to inhibition by aminocoumarins, while
      topoisomerase IV is much less sensitive. Modern genetic techniques have allowed
      the engineering of the producer strains, resulting in a diverse range of new
      aminocoumarins, including compounds which are more active than the natural
      antibiotics as well as a compound which is actively imported across the cell
      envelope of Gram-negative bacteria. A further group of aminocoumarins are the
      simocyclinones which bind simultaneously to two different sites of gyrase and
      show a completely new mode of inhibition. Both the simocyclinones and the
      "classical" aminocoumarins strongly inhibit the fluoroquinolone-induced
      activation of RecA and thereby the SOS response in S. aureus. Therefore, a
      combination of aminocoumarins and fluoroquinolones strongly reduced the risk of
      resistance development and may offer new prospects in anti-infective therapy. 

PMID- 24079981
TI  - Corallopyronin A - a promising antibiotic for treatment of filariasis.
AB  - Lymphatic filariasis and onchocerciasis are diseases of severe morbidity that
      affect the poorest of the poor in the world. The diseases are caused by filarial
      nematodes that are transmitted by mosquitoes or biting blackflies and are endemic
      to more than 80 countries worldwide, mainly in the tropics and sub-tropics.
      Current control programs aim to eliminate the diseases by distributing
      antifilarial drugs. However, the primary effect of the drugs is to kill the
      microfilariae in the blood or skin, thus preventing uptake by the obligate insect
      vector. Since the adult worms live 10 years or longer, drug distribution requires
      many years of treatment, which is a heavy burden on the burgeoning health care
      systems. Sub-optimal response, possible resistance and inadequate population
      coverage lessen the chances for successful elimination in all endemic areas. The
      search for new drugs that could enhance elimination by permanently sterilizing or
      killing adult worms has identified the Wolbachia intracellular bacteria of
      filarial nematodes as a target. Depleting the obligate endosymbionts from the
      worms with doxycycline or rifampicin causes a permanent block in oogenesis,
      embryogenesis and development, and in slow death of the adult worms. These two
      antibiotics are suitable for individual drug administration, but caveats exist
      for their inclusion in broader drug administration programs. Here we review
      Wolbachia as targets for antifilarial drug discovery and highlight the natural
      product corallopyronin A as an effective drug that is currently being developed
      specifically for use against filarial nematodes. 

PMID- 24079982
TI  - Spectro-refractometry of individual microscopic objects using swept-source
      quantitative phase imaging.
AB  - We present a novel spectroscopic quantitative phase imaging technique with a
      wavelength swept-source, referred to as swept-source diffraction phase microscopy
      (ssDPM), for quantifying the optical dispersion of microscopic individual
      samples. Employing the swept-source and the principle of common-path
      interferometry, ssDPM measures the multispectral full-field quantitative phase
      imaging and spectroscopic microrefractometry of transparent microscopic samples
      in the visible spectrum with a wavelength range of 450-750 nm and a spectral
      resolution of less than 8 nm. With unprecedented precision and sensitivity, we
      demonstrate the quantitative spectroscopic microrefractometry of individual
      polystyrene beads, 30% bovine serum albumin solution, and healthy human red blood
      cells. 

PMID- 24079983
TI  - Lower leg weakness as the presentation of infective endocarditis with septic
      emboli.
AB  - Lower leg weakness is a common and nonspecific complaint that encompasses a broad
      differential diagnosis at emergency department, which includes neurologic aspect
      and a wide range of nonneurologic conditions. Infective endocarditis usually
      presented with variable symptoms emphasizing constitutional complaints, or
      complaints that focus on primary cardiac effects or secondary embolic phenomena.
      Underdiagnosis of the disease can lead to clinical catastrophe and even death. By
      far, it is rarely considered in the differential diagnosis of lower leg weakness.
      Herein, we present a case of a 56-year-old man who came to our emergency
      department with a chief concern of lower leg weakness, which was actually the
      result of L-spine osteomyelitis and spondylodiscitis as complications of
      infective endocarditis with septic emboli.

PMID- 24079984
TI  - Infective rhomboencephalitis and inverted Takotsubo: neurogenic-stunned
      myocardium or myocarditis?
AB  - Here we originally describe the clinical scenario of a young immune-competent
      patient affected by acute rhomboencephalitis with severe parenchymal edema and
      acute hydrocephalus who developed sudden life-threatening cardiac derangement.
      Hemodynamic and perfusion parameters revealed cardiogenic shock, so intensive
      circulatory support with epinephrine infusion and intra-aortic balloon pump was
      needed to restore organ perfusion. Transesophageal echocardiographic examination
      showed severe left ventricular dysfunction (ejection fraction as low as 20%) with
      wall motion abnormalities resembling a pattern of Takotsubo-inverted
      cardiomyopathy. Cultural investigations revealed infection by Listeria
      monocytogenes. Nevertheless, her conditions rapidly improved, and she had full
      cardiac recovery within few days. Acute cerebral damage, pattern of
      echocardiographic wall motion abnormalities, and clinical course may suggest
      neurogenic stunned as pathological mechanism responsible for cardiac dysfunction,
      but differential diagnosis with acute myocarditis is to be considered too. Acute
      cardiogenic shock during the course of rhomboencephalitis by L monocytogenes has
      not been yet reported; prompt clinical suspicion and intensive care are needed to
      manage this life-threatening condition.

PMID- 24079985
TI  - Automatic chest compression devices--when do they make sense?
AB  - The current resuscitation guidelines of the European Resuscitation Council do not
      include automatic chest compression devices (ACDs) as standard equipment to
      support cardiopulmonary resuscitation attempts. One possible reason could be the
      lack of a list of indications and contraindications for the use of ACD systems.
      This review should give a summary of current studies and developments according
      to ACD systems and deliver a list of possible applications. Furthermore, we
      discuss some ethical problems with cardiopulmonary resuscitation attempts and, in
      particular, with ACD systems. The use of ACDs occurs instead of manual chest
      compression. Because of this, there is no reason for changing the current
      guidelines, especially termination recommendations while using ACD systems. From
      our point of view, ACDs are a very good supplement to the current standard of
      resuscitation according to the European Resuscitation Council guidelines. 

PMID- 24079986
TI  - Unilateral neck pain: a case of Eagle syndrome with associated nontraumatic
      styloid fracture.
AB  - We present a case of Eagle syndrome in a 77-year-old woman with associated
      aneurysm and nontraumatic styloid process fracture, without history of
      tonsillectomy, who presented to the emergency department. The first set of
      symptoms associated with the elongation of the temporal styloid process and/or
      the calcification of the stylomandibular or stylohyoid ligaments was described by
      Eagle in 1937. Classically, unilateral pain in the oropharynx radiating to the
      neck and face that is exacerbated by head turning and neck rotation is
      characteristic of Eagle syndrome. However, styloid process elongation and
      stylohyoid calcification found in Eagle syndrome may also present with vascular
      symptomsthrough impingement and injury of the carotid arteries. Eagle syndrome is
      a rare but important differential that the emergency physician must consider in a
      patient with unilateral neck pain and positional neurological symptoms with head
      turning and in posttonsillectomy patients. Patients with medical history of Eagle
      syndrome presenting with neck pain and especially neurological symptomsmust be
      thoroughly evaluated for carotid and jugular venous injury. Specifically, the
      decision to obtain computed tomography and computed tomographic angiography to
      evaluate for carotid artery injury is important for patient management and
      disposition.

PMID- 24079987
TI  - Human intravenous injection of beta-cyfluthrin with minimal toxic effects.
AB  - A 28-year-old man presented to the emergency department (ED) 20 minutes after
      injecting 20 mL of an insecticide containing 0.05% beta-cyfluthrin. Upon
      presentation, he had no complaints; and vital signs demonstrated a sinus
      tachycardia of 150 beats per minute, blood pressure of 140/65 mm Hg, no fever,
      and a normal respiratory rate. Further physical examination was notable only for
      the lack of tremor and the presence of a left antecubital recent injection site.
      The patient denied use of other drugs that day, but admitted to recent use of
      methamphetamine. He was taking oxcarbazepine, lurasidone, and venlafaxine for
      reported bipolar affective disorder and schizophrenia. The ED evaluation included
      an electrocardiogram demonstrating sinus tachycardia, undetectable acetaminophen
      and salicylate levels, and a urine drug screen that was positive for
      methamphetamine and tetrahydrocannabinol. The patient was treated with an
      intravenous fluid bolus of 2000 mL and observed in the ED. Over the course of the
      subsequent 3 hours, his pulse rate went down to 90/min. He remained asymptomatic
      and was transferred to the Psychiatric Assessment Unit after approximately 6
      hours of observation. We present the first published case of cyfluthrin
      parenteral human injection. Although this patient experienced a benign clinical
      course, vigilance for pyrethroid toxic effects such as seizures, severe tremors,
      diaphoresis, and choreoathetosis is paramount.

PMID- 24079988
TI  - Myasthenia gravis and Guillain-Barre co-occurrence syndrome.

PMID- 24079989
TI  - Caffeine overdose resulting in severe rhabdomyolysis and acute renal failure.
AB  - Despite the fact that caffeine is the most commonly used stimulant in modern
      society, cases of caffeine overdose are relatively rare, with fatalities reported
      from doses of 10 g and higher (Nord J Psychiatry. 2006;60:97-106). Large doses
      produce symptoms associated with stimulation of the cardiovascular, central
      nervous, and gastrointestinal symptoms (Associates of the California Poison
      Control Center, Poisoning and Drug Overdose, pp. 142-143. 5th Ed). We present the
      first reported case of a man with delayed presentation to the emergency
      department after ingesting 24 g of caffeine in a suicide attempt who suffered
      complications of severe rhabdomyolysis and acute renal failure requiring
      subsequent hemodialysis.

PMID- 24079990
TI  - Transient left ventricular and stomach apical ballooning syndromes: when the
      trigger is also a clinical emergency.
AB  - A 59-year-old woman was referred to our emergency department because of
      epigastric pain and incoercible vomit. Electrocardiogram showed ST-segment
      elevation in anterior-lateral leads, but coronary angiogram revealed normal
      coronary tree and left ventricular angiography showed apical and midventricular
      akinesis with preserved basal systolic function: a diagnosis of apical ballooning
      syndrome was made. During the following days, the patient complained about
      persistent abdominal pain, and a nasogastric tube drained more than 1000 cc of
      dark fecaloid material. Urgent abdominal computed tomography scan showed a mural
      thrombus in the apex of the left ventricle and a huge diaphragmatic hernia
      through which more than one-half of the stomach was herniated and presented a
      sort of "apical stomach ballooning." Gastropexy was done; surgical diagnosis was
      a type IV giant diaphragmatic hernia complicated by recent gastric volvulus
      caused by rotation along the longitudinal cardiopyloric axis. Type IV giant
      diaphragmatic hernia is relatively rare, representing only about 5% to 7% of all
      hernias. Gastric volvulus is a severe complication, with acute mortality reported
      to be as high as 30% to 50%. In our case, a severe life-threatening condition as
      gastric volvulus triggered an apical ballooning syndrome, a transient
      cardiomyopathy, usually induced by emotional stressors with a long-term good
      prognosis. Apical ballooning syndrome must be considered an epiphenomenon of
      other organic diseases that may have an important role in the prognosis of the
      patient not only in acute but also in chronic setting. Only early determination
      of the true cause of apical ballooning syndrome ensures a proper treatment.

PMID- 24079991
TI  - [A phenomenological approach of treatment-resistant depressions].
AB  - BACKGROUND: Hospital practitioners are regularly facing treatment-resistant
      depression, which may be defined according to the clinical picture or according
      to the therapeutic strategy. There are different levels of resistance and
      different levels of evidence for this resistance. Indeed, the notions of relative
      and absolute resistance describe the adequacy of assigned treatment. It thus
      seems necessary to specify the psychopathology of treatment-resistant depression
      and to highlight the endogeneity phenomenon in order to solve this problem.
      OBJECTIVE: Our work addresses the concept of endogeneity (previously clarified by
      Hubertus Tellenbach) and will consider its implications in the management of
      treatment-resistant depression. We attempt to demonstrate that the
      phenomenological approach is an interesting tool in clinical practice through the
      highlight of endogenous characteristics. METHOD: The first step consists in
      specifying the endogenous phenomena: abolition of rhythms, loss of the forward
      looking deployment, overall impression, and reversibility, spatial and temporal
      characteristics from the phenotype. Our phenomenological approach continues by
      exploring the false resistances. Hence, we take into account anxious comorbidity,
      medical comorbidity, addictions, personality disorders and the hypothesis of a
      bipolar diathesis. First of all, it is difficult to show the patient in which way
      their behaviour results in stagnation. Indeed, it could strengthen the internal
      move that leads to an imperious necessity to cope with the surroundings. The
      psychotherapeutic help is elaborated by specifically highlighting the pathogenic
      situations whilst also taking into account the difficulties of an authentic
      therapeutic alliance. RESULTS: Our approach emphasizes the endogeneity phenomenon
      in depression, permitting the search for an optimal therapeutic strategy. It also
      provides assistance in resolving false resistance or what is apparent. In cases
      of endogenous depression, therapeutic orientation favours pharmacological and
      instrumental strategies (brain stimulation). If elements of self-understanding
      can be given to the patient, they must show that the rigid way in which the
      patient appropriates the daily reports is more stressful than the choice.
      Therefore, the psychotherapeutic help must take into account the situation and
      the individual vulnerability so as to develop a suitable care.

PMID- 24079992
TI  - The PROCESS study: a protocol to evaluate the implementation, mechanisms of
      effect and context of an intervention to enhance public health centres in Tororo,
      Uganda.
AB  - BACKGROUND: Despite significant investments into health improvement programmes in
      Uganda, health indicators and access to healthcare remain poor across the
      country. The PRIME trial aims to evaluate the impact of a complex intervention
      delivered in public health centres on health outcomes of children and management
      of malaria in rural Uganda. The intervention consists of four components: Health
      Centre Management; Fever Case Management; Patient- Centered Services; and support
      for supplies of malaria diagnostics and antimalarial drugs. METHODS: The PROCESS
      study will use mixed methods to evaluate the processes, mechanisms of change, and
      context of the PRIME intervention by addressing five objectives. First, to
      develop a comprehensive logic model of the intervention, articulating the
      project's hypothesised pathways to trial outcomes. Second, to evaluate the
      implementation of the intervention, including health worker training, health
      centre management tools, and the supply of artemether-lumefantrine (AL) and rapid
      diagnostic tests (RDTs) for malaria. Third, to understand mechanisms of change of
      the intervention components, including testing hypotheses and interpreting
      realities of the intervention, including resistance, in context. Fourth, to
      develop a contextual record over time of factors that may have affected
      implementation of the intervention, mechanisms of change, and trial outcomes,
      including factors at population, health centre and district levels. Fifth, to
      capture broader expected and unexpected impacts of the intervention and trial
      activities among community members, health centre workers, and private providers.
      Methods will include intervention logic mapping, questionnaires, recorded
      consultations, in-depth interviews, focus group discussions, and contextual data
      documentation. DISCUSSION: The findings of this PROCESS study will be interpreted
      alongside the PRIME trial results. This will enable a greater ability to
      generalise the findings of the main trial. The investigators will attempt to
      assess which methods are most informative in such evaluations of complex
      interventions in low-resource settings. TRIAL REGISTRATION: Clinicaltrials.gov,
      NCT01024426.

PMID- 24079993
TI  - Examining neural plasticity and cognitive benefit through the unique lens of
      musical training.
AB  - Training programs aimed to alleviate or improve auditory-cognitive abilities have
      either experienced mixed success or remain to be fully validated. The limited
      benefits of such regimens are largely attributable to our weak understanding of
      (i) how (and which) interventions provide the most robust and long lasting
      improvements to cognitive and perceptual abilities and (ii) how the neural
      mechanisms which underlie such abilities are positively modified by certain
      activities and experience. Recent studies indicate that music training provides
      robust, long-lasting biological benefits to auditory function. Importantly, the
      behavioral advantages conferred by musical experience extend beyond simple
      enhancements to perceptual abilities and even impact non-auditory functions
      necessary for higher-order aspects of cognition (e.g., working memory,
      intelligence). Collectively, preliminary findings indicate that alternative forms
      of arts engagement (e.g., visual arts training) may not yield such widespread
      enhancements, suggesting that music expertise uniquely taps and refines a
      hierarchy of brain networks subserving a variety of auditory as well as domain
      general cognitive mechanisms. We infer that transfer from specific music
      experience to broad cognitive benefit might be mediated by the degree to which a
      listener's musical training tunes lower- (e.g., perceptual) and higher-order
      executive functions, and the coordination between these processes. Ultimately,
      understanding the broad impact of music on the brain will not only provide a more
      holistic picture of auditory processing and plasticity, but may help inform and
      tailor remediation and training programs designed to improve perceptual and
      cognitive benefits in human listeners.

PMID- 24079994
TI  - AMPA receptors mediate passive avoidance deficits induced by sleep deprivation.
AB  - The present study addressed the effects of sleep deprivation (SD) on AMPA
      receptor (AMPAR) binding in brain regions associated with learning and memory,
      and investigated whether treatment with drugs acting on AMPAR could prevent
      passive avoidance deficits in sleep deprived animals. [(3)H]AMPA binding and
      GluR1 in situ hybridization signals were quantified in different brain regions of
      male Wistar rats either immediately after 96 h of sleep deprivation or after 24h
      of sleep recovery following 96 h of sleep deprivation. Another group of animals
      were sleep deprived and then treated with either the AMPAR potentiator,
      aniracetam (25, 50 and 100mg/kg, acute administration) or the AMPAR antagonist
      GYKI-52466 (5 and 10mg/kg, acute and chronic administration) before passive
      avoidance training. Task performance was evaluated 2h and 24h after training. A
      significant reduction in [(3)H]AMPA binding was found in the hippocampal
      formation of SD animals, while no alterations were observed in GluR1 mRNA levels.
      The highest dose of aniracetam (100mg/kg) reverted SD-induced impairment of
      passive avoidance performance in both retention tests, whereas GYKI-52466
      treatment had no effect. Pharmacological enhancement of AMPAR function may revert
      hippocampal-dependent learning impairments produced after SD. We argue that such
      effects might be associated with reduced AMPAR binding in the hippocampus of
      sleep deprived animals.

PMID- 24079995
TI  - Type II pyrethroid deltamethrin produces antidepressant-like effects in mice.
AB  - Pyrethroids, which are widely used insecticides with low acute toxicity in
      mammals, affect sodium channels in neurons. In primary culture of rat cortical
      neurons, the type II pyrethroid deltamethrin (DM) markedly enhances the
      expression of the mRNA of brain-derived neurotrophic factor (BDNF) and exerts
      neurotrophic effects. In this study, we investigated the antidepressant-like
      effect of DM in mice. The effects of DM were assessed using the forced swimming
      test (FST) and were compared with those of type I pyrethroid permethrin (PM).
      Intraperitoneal administration of DM (5 and 10mg/kg), but not of PM (10mg/kg),
      increased the expression of BDNF mRNA in the hippocampus. DM, but not PM,
      significantly decreased the immobility time in the FST, and did not affect
      locomotor activity and motor coordination, suggesting that DM has an
      antidepressant-like effect. This effect of DM was inhibited by
      intracerebroventricular injection of K252a, which is an inhibitor of the BDNF
      receptor TrkB, indicating that the antidepressant-like effects of DM are mediated
      by BDNF/TrkB signaling pathways. Repeated administration of DM, but not of PM,
      also exerted antidepressant-like effects, which were long lasting. The results of
      the present study suggest that DM possesses antidepressant-like properties, and
      may be a possible source for the development of drugs to treat neurodegenerative
      and psychiatric disorders including depression. 

PMID- 24079996
TI  - Different locomotor sensitization responses to repeated cocaine injections are
      associated with differential phosphorylation of GluA1 in the dorsomedial striatum
      of adult rats.
AB  - Behavioral sensitization to psychostimulants reflects neural adaptation, which
      might share a common mechanism with drug addiction. Outbred male rats show
      different locomotor sensitization responses to cocaine, and cocaine also produces
      varied addictive progress in humans. We investigated whether differences in the
      induction of sensitization would affect the long-term persistence of sensitized
      locomotor activity, and we sought to determine the molecular basis for the
      variability in sensitization. Male Sprague-Dawley rats that showed sensitized
      locomotor responses over 5 consecutive daily cocaine injections (SENS) had
      significantly lower initial locomotor responses to the 1st cocaine exposure than
      did rats that did not show locomotor sensitization (NONS). Furthermore, rats that
      underwent 1 month of cocaine withdrawal after 5 repeated cocaine injections also
      exhibited sensitized or non-sensitized locomotor responses to a challenge
      injection of cocaine (SENS-C or NONS-C, respectively). This variability was also
      related to the initial responsiveness to cocaine. We examined the level of
      phosphorylation of the GluA1 subunit of alpha-amino-3-hydroxy-5-methyl-4
      isoxazolepropioniate receptor (AMPAR) in the dorsal striatum and found that there
      were significant differences between the sensitized rats and the non-sensitized
      rats. pGluA1-Ser831 was increased in the SENS rats during the induction of
      locomotor sensitization, and pGluA1-Ser845 was increased in the SENS-C rats
      during the expression of locomotor sensitization. These phosphorylation changes
      were observed in the dorsomedial striatum (DMS) of adult rats but not in the
      dorsolateral striatum (DLS) of adults. Our findings suggest that differential
      phosphorylation of AMPAR might be an important mechanism that contributes to the
      development of locomotor sensitization to cocaine in adult rats.

PMID- 24079997
TI  - Photodegradation of Acid Orange 7 in a UV/acetylacetone process.
AB  - Acetylacetone (AcAc) was employed as a photo-activator for the degradation of
      Acid Orange 7 (AO7) under UV irradiation. The feasibility of this process (named
      as UV/AcAc) was evaluated through comparison with the well-established UV/H2O2
      process in terms of absorption spectrum and the biodegradability of the
      solutions. A complete decoloration of the AO7 solution could be fulfilled with
      AcAc at mM level. A self-acceleration phenomenon was observed for the UV/AcAc
      process. The pseudo first-order decoloration rate constant of AO7 in the UV/AcAc
      process was several times higher than that in the UV/H2O2 process, depending on
      the irradiation conditions. The BOD to COD ratio of the solutions increased from
      below 0.1 to above 0.3, along with a slight mineralization. Based on degradation
      product analysis, the possible pathways for AO7 degradation in the UV/AcAc
      process were proposed. 

PMID- 24079998
TI  - The swimming speed alteration of two freshwater rotifers Brachionus calyciflorus
      and Asplanchna brightwelli under dimethoate stress.
AB  - Two common freshwater rotifer species Brachionus calyciflorus and Asplanchna
      brightwelli were employed as test organisms to investigate the toxic effects of
      the widely used organophosphate pesticide, dimethoate. The swimming angular speed
      and linear speed alteration of two rotifers were evaluated under the toxic stress
      in four concentrations (0.4, 0.8, 1.2, and 1.6 mg L(-1)). For B. calyciflorus,
      the rotifer swimming angular speed and linear speed were both adversely affected
      as a function of the toxicant concentrations. After a 2h exposure, the angular
      speeds at four concentrations were 39.37, 30.74, 26.68 and 23.96 degrees  s(-1),
      65.30%, 50.98%, 44.25% and 39.74% of that of the control, respectively, while the
      mean linear speed decreased from 194.80 to 91.85*10(-3) mm s(-1), which was
      70.12%, 48.14%, 34.02% and 33.06% of that of the control (277.82*10(-3) mm s(
      1)), respectively. The pesticide also significantly inhibited the swimming
      angular speed of A. brightwelli. After a 2h exposure, the angular speeds of this
      rotifer at four concentrations were 39.37, 30.74, 26.68 and 23.96 degrees  s(-1),
      only 22.99%, 17.16%, 16.21% and 13.63% of that of the control (170.80 degrees  s(
      1)), respectively. Compared with the results of B. calyciflorus, A. brightwelli
      was more sensitive on the swimming angular speed when exposed to the toxicant. It
      implied that A. brightwelli should be an alternative candidate model species
      about the toxicities of aquatic pollutants. In addition, when the rotifer A.
      brightwelli was exposed to four pesticide concentrations, the swimming linear
      speed displayed symptoms of hormesis, characterized by the conversion of low
      concentration stimulate to high-concentration inhibition. Our results show that
      dimethoate had a significant effect on swimming of freshwater rotifers.

PMID- 24079999
TI  - Pathways and speciation of mercury in the environmental compartments of Deception
      Island, Antarctica.
AB  - This work reports the first integrated mercury study in an Antarctic ecosystem.
      Sample collection took place in Deception Island, an active volcano in the South
      Shetland Islands, in several environmental compartments (water, snow, sediments
      and vegetation) and different locations, during December 2011. The results
      suggest that volcanic activity is the most important Hg source. Mercury levels in
      water and sediments sampled at two fumaroles were up to 10,000 times higher than
      in the other sampling sites. Dissolved methylmercury (MeHg) is below the
      detection limit in those samples, probably due to the very high temperature found
      in fumaroles (above 80  degrees C). On the other hand MeHg accounted for, on
      average, 23% of total dissolved Hg in the saline waters of Foster bay, which
      suggests exceptional conditions for Hg methylation. Combined with the high
      residence time of the water in Foster bay, the results point to the existence of
      a MeHg pool available for aquatic living organisms.

PMID- 24080000
TI  - Locomotor activity changes on zebrafish larvae with different 2,2',4,4'
      tetrabromodiphenyl ether (PBDE-47) embryonic exposure modes.
AB  - Polybrominated diphenyl ethers (PBDEs) are widely used flame retardants and are
      banned around the world as potent environmental contaminants. PBDE-47 is the most
      concerned PBDE with its environmental prevalence and various toxicity
      characteristics including neurotoxicity. In this paper, we studied larval
      zebrafish behavioral alterations caused by PBDE-47 neurotoxicity. The light-dark
      cycle stimulation was used to investigate the locomotor changes of zebrafish
      larvae at different ages (4-6 day post-fertilization, dpf) after PBDE-47 exposure
      (5, 50, 500 MUg L(-1)). Three exposure modes, namely continuous exposure, early
      pulse exposure and interval exposure, were adopted to assess and compare the
      impacts of exposure modes on larval zebrafish locomotion. Our results showed that
      locomotor effects upon PBDE exposure depended on the specific exposure mode
      studied. In the early pulse exposure mode, the locomotion of zebrafish larvae did
      not change significantly at all PBDE-47 concentrations tested. In contrast, for
      both the continuous exposure and interval exposure modes, the highest dose of
      PBDE-47 (500 MUg L(-1)) elicited pronounced hypoactivity at 5 dpf during dark
      periods except for the initial one. However, at 6 dpf, hypoactivity was only
      observed in the continuously exposed zebrafish larvae (to an even higher degree
      compared to 5 dpf), but not in the interval exposure treatment group. Our results
      suggested that the conventional, continuous exposure mode might not be enough to
      evaluate the toxicity of chemicals in the real environments.

PMID- 24080001
TI  - Photo-induced oxidation of Sb(III) on goethite.
AB  - Goethite widely exists in soils and sediments, and plays a very important role in
      the environmental fate of toxic metal(loid)s. In the present study, photo-induced
      oxidation of antimonite [Sb(III)] on goethite was investigated with kinetic
      measurements and X-ray photoelectron spectroscopy (XPS) techniques. Effects of
      environmental factors including solution pH, the content of goethite as well as
      humic acid on the photo-induced oxidation of antimonite were tested. The results
      indicated that no oxidation of antimonite occurred in goethite suspension in the
      dark, but significant amounts of antimonite were transformed to antimonate when
      the suspension was exposed to light. Ferrous ions were found in the solution
      during the antimonite oxidation process, and its concentration decreased with
      increasing solution pH, which strongly affected the oxidation rate of antimonite.
      The initial solution pH has great impact on Sb oxidation. After 2h illumination,
      the highest oxidation rate was found at pH 3, while the initial oxidation rate
      was even higher at pH 9. In conclusion, the antimonite can be adsorbed and
      oxidized on goethite irradiated with light, which will greatly reduce its
      environmental risk.

PMID- 24080002
TI  - Enantioselective degradation of metalaxyl in cucumber, cabbage, spinach and
      pakchoi.
AB  - The enantioselective degradation behaviors of the acylamino acid fungicide
      metalaxyl in vegetables (cucumber, cabbage, spinach and pakchoi) under field and
      greenhouse conditions were elucidated by reversed-phase high-performance liquid
      chromatography (HPLC). A cellulose tris (3-chloro-4-methyl phenyl carbamate)
      chiral column (Lux Cellulose-2) was used for the chiral separation of the
      enantiomers using acetonitrile-0.1% formic acid solution (40:60, v/v) as mobile
      phase at a flow rate of 1.0 mL min(-1). The two enantiomers could be completely
      separated with a resolution (Rs) of 5.2. The linearity range, matrix effect,
      precision and recovery were evaluated. The method was successfully applied for
      the enantioselective analysis of metalaxyl in cucumber, cabbage, spinach and
      pakchoi under different conditions. The results showed that R-enantiomer
      dissipated faster than S-enantiomer in cucumber of greenhouse. Inversely, a
      preferential degradation of S-form was found in spinach and pakchoi under field
      and greenhouse conditions. No stereoselective degradation in cabbage was
      observed. These results can be applied for evaluating the environmental risk and
      food safety.

PMID- 24080003
TI  - A pilot study for foetal exposure to multiple persistent organic pollutants and
      the development of infant atopic dermatitis in modern Japanese society.
AB  - Increasing evidence supports that harmful chemicals accumulating in the human
      body may pose a significant threat to infant health through foetal exposure.
      Persistent organic pollutants (POPs) are thought to enhance the risk for later
      development of allergic disease like atopic dermatitis (AD). However, few studies
      have evaluated the effect of foetal exposure to various POPs on the development
      of AD in early infancy. Here, we describe the impact of foetal exposure to a
      number of POPs on the occurrence of AD in 7-month-old infants. The participants
      were 81 infants with or without AD who participated in a birth cohort study,
      where the concentrations of 15 polychlorinated biphenyl (PCBs) congeners,
      dichlorodiphenyltrichloroethane (p,p'-DDT), dichlorodiphenyldichloroethylene
      (p,p'-DDE), beta-hexachlorocyclohexane (beta-HCH), hexachlorobenzene (HCB), cis
      nonachlor, trans-nonachlor, mirex, oxychlordane, and 27 polybrominated diphenyl
      ether (PBDEs) congeners were measured in the umbilical cord tissues collected
      immediately after birth. At 7 months, 27 of the 81 infants (33.8%) were diagnosed
      with AD. Of all POPs examined, total concentrations of 27 PBDE congeners were
      associated with a significantly decreased incidence of AD. Notably, the
      concentration of 27 PBDEs was significantly lower in AD infants than in non-AD
      infants (P<0.01), and the risk of AD development decreased with increasing PBDE
      levels. These results suggest that foetal exposure to PBDEs is a possible
      contributing factor to reducing AD in early infancy.

PMID- 24080004
TI  - Lifetime PCB 153 bioaccumulation and pharmacokinetics in pilot whales: Bayesian
      population PBPK modeling and Markov chain Monte Carlo simulations.
AB  - Physiologically based pharmacokinetic (PBPK) models for wild animal populations
      such as marine mammals typically have a high degree of model uncertainty and
      variability due to the scarcity of information and the embryonic nature of this
      field. Parameters values used in marine mammals models are usually taken from
      other mammalian species (e.g. rats or mice) and might not be entirely suitable to
      properly explain the kinetics of pollutants in marine mammals. Therefore, several
      parameters for a PBPK model for the bioaccumulation and pharmacokinetics of PCB
      153 in long-finned pilot whales were estimated in the present study using the
      Bayesian approach executed with Markov chain Monte Carlo (MCMC) simulations. This
      method uses 'prior' information of the parameters, either from the literature or
      from previous model runs. The advantage is that this method uses such 'prior'
      parameters to calculate probability distributions to determine 'posterior' values
      that best explain the field observations. Those field observations or datasets
      were PCB 153 concentrations in blubber of long-finned pilot whales from Sandy
      Cape and Stanley, Tasmania, Australia. The model predictions showed an overall
      decrease in PCB 153 levels in blubber over the lifetime of the pilot whales. All
      parameters from the Sandy Cape model were updated using the Stanley dataset,
      except for the concentration of PCB 153 in the milk. The model presented here is
      a promising and preliminary start to PBPK modeling in long-finned pilot whales
      that would provide a basis for non-invasive studies in these protected marine
      mammals. 

PMID- 24080005
TI  - Imbalance between oxidative and antioxidative systems: toward an understanding of
      visible light-induced titanium dioxide nanoparticles toxicity.
AB  - The broad application of titanium dioxide nanoparticles (TiO(2) NPs) has resulted
      in the release of substantial quantities of untreated TiO(2) NPs into aquatic
      systems, which serve as the terminal sink for nanomaterials. These TiO(2) NPs may
      induce some unexpected toxic effects to aquatic systems. The objectives of this
      research were to evaluate toxic effects of low dosage TiO(2) NPs on Tetrahymena
      pyriformis under visible-light illumination conditions and further discuss
      possible mechanisms. The results showed that TiO(2) NPs accumulated as aggregates
      in cytosolic vesicles of T. pyriformis. Cell numbers and viability of TiO(2) NPs
      exposed groups decreased to (20.2 +/- 1.8)% and (17.3 +/- 1.9)% after 24h
      continuous 12000 Lx illumination. Compared with the dark control, the
      intracellular reactive oxygen species (ROS) levels increased (1.9-fold) by the
      combination of 5 mg L(-1) TiO(2) NPs and 12000 Lx illumination. Even incubation
      in the dark for 6h after 12h illumination, superoxide dismutase (SOD) activity of
      TiO(2) NPs exposed groups still maintained at the high level (about 3.9-fold of
      dark control). Meanwhile, illumination-induced TiO(2) NPs led to a reduction of
      scavenging hydroxyl radicals (OH) activity with an average of (14.3 +/- 6.5)%.
      Under illumination conditions, overproduction of reactive oxygen species (ROS) by
      TiO(2) NPs exceeded the scavenging capability of T. pyriformis and then led to
      the breakdown of oxidative/anti-oxidative systems, further resulting in cell
      growth delay and mitochondria dysfunction. All the results revealed that via
      visible light excitation, oxidative injury may be responsible for the toxic
      effects of TiO(2) NPs on T. pyriformis.

PMID- 24080006
TI  - Temperature threshold of isoprene emission from tropical trees, Ficus virgata and
      Ficus septica.
AB  - This paper describes the existence of temperature threshold in isoprene emission
      from tropical trees for the first time. Isoprene emission capacity of Ficus
      virgata leaves kept outdoors were measured over a period of 20 d in the
      wintertime. When the plants experienced the low temperature below 12  degrees C
      in the daytime, isoprene emission was completely suppressed, and re-activated by
      elevated temperature above the threshold of 12  degrees C. Photosynthesis is also
      decreased similarly, but too much smaller extent compared to the reduction
      observed for isoprene emission. The cut off level of accumulated temperature to
      shut off the isoprene emission was roughly estimated to be 300 degree/d. The shut
      off in the isoprene emission by the low temperature was confirmed experimentally
      by use of phytotron with tropical trees of F. virgata and F. septica. Isoprene
      emission of both species ceased at 12  degrees C, and re-activated by raising the
      temperature above the threshold level. Photosynthesis was lowered slightly as was
      the case for the field observation, and no close association between
      photosynthesis and isoprene emission was noted. The expression of isoprene
      synthase gene showed much greater variation after exposure to the cold
      temperature compared to those involved in photosynthesis. These observations
      therefore suggested the existence of putative direct connection between
      perception of temperature and isoprene emission in tropical trees, which may
      merit further investigation to estimate the net output of isoprene from
      subtropical or tropical forest.

PMID- 24080007
TI  - The transformation mechanism of nitrobenzene in the present of a species of
      cyanobacteria Microcystis aeruginosa.
AB  - The transformation mechanism of nitrobenzene (NB) with Microcystis aeruginosa was
      investigated by a series of laboratory-scale experiments. The result showed only
      a small fraction of NB can be adsorbed by M. aeruginosa. The adsorption was
      responsible to the transformation of NB in M. aeruginosa solution but was not the
      primary cause. The variation of cell activity and illumination could affect the
      transformation of NB with M. aeruginosa, which indicated that M. aeruginosa have
      the ability to biodegrade NB. Metabolic intermediate products analysis indicated
      that M. aeruginosa can reduce NB to aniline (AN), and NB reductase, induced by
      NB, was the key enzyme during the reduction process. M. aeruginosa cannot further
      degrade AN and may prevent the volatilization of AN, causing the accumulation of
      AN in the solution for up to 3 days. Only a small proportion of AN (less than 5%)
      can be degraded to acetaldehyde and acetone by photolysis in 48 h. The total
      concentration of nitrogen aromatic compounds is invariant at first, and then
      decreases after 72 h incubation via a complex process including adsorption,
      biodegradation, volatilization and photolysis processes.

PMID- 24080008
TI  - Incorporating bioavailability into management limits for copper in sediments
      contaminated by antifouling paint used in aquaculture.
AB  - Although now well embedded within many risk-based sediment quality guideline
      (SQG) frameworks, contaminant bioavailability is still often overlooked in
      assessment and management of contaminated sediments. To optimise management
      limits for metal contaminated sediments, we assess the appropriateness of a range
      methods for modifying SQGs based on bioavailability considerations. The
      impairment of reproduction of the amphipod, Melita plumulosa, and harpacticoid
      copepod, Nitocra spinipes, was assessed for sediments contaminated with copper
      from antifouling paint, located below aquaculture cages. The measurement of
      dilute acid-extractable copper (AE-Cu) was found to provide the most useful means
      for monitoring the risks posed by sediment copper and setting management limits.
      Acid-volatile sulfide was found to be ineffective as a SQG-modifying factor as
      these organisms live mostly at the more oxidised sediment water interface. SQGs
      normalised to %-silt/organic carbon were effective, but the benefits gained were
      too small to justify this approach. The effectiveness of SQGs based on AE-Cu was
      attributed to a small portion of the total copper being present in potentially
      bioavailable forms (typically<10% of the total). Much of the non-bioavailable
      form of copper was likely present as paint flakes in the form of copper (I)
      oxide, the active ingredient of the antifoulant formulation. While the
      concentrations of paint-associated copper are very high in some sediments, as the
      transformation of this form of copper to AE-Cu appears slow, monitoring and
      management limits should assess the more bioavailable AE-Cu forms, and further
      efforts be made to limit the release of paint particles into the environment. 

PMID- 24080009
TI  - Genotoxicity of quinolones: substituents contribution and transformation products
      QSAR evaluation using 2D and 3D models.
AB  - The genotoxicity of 21 quinolones antibiotics was determined using SOS/umu assay.
      Some quinolones exhibited high genotoxicity, and the chemical substituent on
      quinolone ring significantly affected genotoxicity. To establish the relationship
      between genotoxicity and substituent, a 2D-QSAR model based on quantum chemical
      parameters was developed. Calculation suggested that both steric and
      electrostatic properties were correlated well with genotoxicity. Furthermore, the
      specific effect on three key active sites (1-, 7- and 8-positions) of quinolone
      ring was investigated using a 3D-QSAR (comparative molecular field analysis,
      CoMFA) method. From our modeling, the genotoxicity increased when substituents
      had: (1) big volume and/or positive charge at 1-position; (2) negative charge at
      7-position; and (3) small volume and/or negative charge at 8-position. The
      developed QSAR models were applicable to estimate genotoxicity of quinolones
      antibiotics and their transformation products. It is noted that some of the
      transformation products exhibited higher genotoxicity comparing to their
      precursor (e.g., ciprofloxacin). This study provided an alternative way to
      understand the molecule genotoxicity of quinolones derivatives, as well as to
      evaluate their potential environmental risks.

PMID- 24080010
TI  - Effects of electrokinetic treatment of contaminated sludge on migration and
      transformation of Cd, Ni and Zn in various bonding states.
AB  - This study assesses the effect of electrokinetic processes on the migration and
      bonding states of various heavy metals in municipal sludge. The transformation
      and migration are discussed through the examination of sludge characteristics and
      distribution of Cd, Zn and Ni after electrokinetic treatments. The migration and
      distribution of the contaminants after the electrokinetic treatments were
      determined for each sludge sample by sequential extraction. The noticeable
      changes on the average speciation fractions of Cd, Zn and Ni were observed that
      oxidizable heavy metals increased and reducible fraction decreased due to the
      application of voltage. Bivariate correlation analysis indicated that the amounts
      of different bonding states of Zn and Ni were significantly correlated (P<0.05)
      with durations and resistance. The oxidizable Zn was negatively correlated with
      exchangeable and reducible Zn. Moreover, reducible Zn had a close negative
      relationship with residual Zn. The bonding state of Ni was significantly related
      to the durations of electrokinetic processes, indicating the existing of mutual
      transformation between different speciation fractions over time. The analysis
      also indicated that the exchangeable Cd showed a close negative relationship with
      reducible Cd (P<0.01), whereas the reducible Cd was negatively related to
      residual Cd (P<0.05). 

PMID- 24080011
TI  - Vitamin supplementation in patients receiving pemetrexed for advanced non-small
      cell lung cancer.

PMID- 24080012
TI  - Pax1 acts as a negative regulator of chondrocyte maturation.
AB  - Paired box gene 1 (Pax1) indirectly promotes the early stages of chondrogenic
      differentiation through induction and transactivation of Nk3 homeobox 2 (Nkx3.2),
      a transcriptional repressor. Later in chondrogenic differentiation, Nkx3.2 blocks
      chondrocyte hypertrophy by repressing Runt-related transcription factor 2
      (Runx2). Here we report the inhibitory action of Pax1 on chondrocyte maturation,
      independently of Nkx3.2. Upon cartilage formation, Pax1 expression in the ventral
      sclerotome was gradually decreased except for the perichondrial region of the
      vertebral bodies and the intervertebral region, both of which express SRY-box
      containing gene 9 (Sox9). Forced expression of Pax1 in the chick forelimb
      resulted in the formation of shortened skeletal elements with a significant
      reduction of proteoglycans (PGs) accumulation in cartilage as well as a lack of
      the cortical bone formation and vascular invasion into the primary ossification
      center. Pax1-misexpressing chondrocytes exhibited aberrant cell morphology with a
      marked downregulation of Aggrecan (Agc1). Pax1-misexpressing cultured
      chondrocytes failed to accumulate cartilaginous PGs and became fibroblastic, in
      association with downregulation of the expression of Sox9, Nkx3.2, Indian
      hedgehog (Ihh), type II collagen (Col2a1), Chondromodulin-1 (Chm1), and Agc1.
      Accumulation of cartilaginous PGs in chondrocytes was also reduced by forced
      expression of Pax1 and Sox9. Thus, chondrocyte maturation driven by Sox9 is
      antagonized by Pax1 that is downregulated during chondrogenic differentiation. 

PMID- 24080013
TI  - BMP4 is required for the initial expression of MITF in melanocyte precursor
      differentiation from embryonic stem cells.
AB  - Although the differentiation of melanoblasts to melanocytes is known to depend on
      many distinct factors, it is still poorly understood which factors lead to the
      induction of melanoblasts. To determine which factors might induce melanoblasts,
      we examined a set of candidate factors for their ability to induce expression of
      MITF, a master regulator of melanoblast development, in an ES cell-based
      melanocyte differentiation system. It appears that BMP4 is capable of inducing
      MITF expression in stem cells. In contrast, a number of other factors normally
      implicated in the development of the melanocyte lineage, including WNT1, WNT3a,
      SCF, EDN3, IGF1, PDGF, and RA, cannot induce MITF expression. Nevertheless, BMP4
      alone does not allow MITF-expressing precursors to become differentiated
      melanocytes, but the addition of EDN3 further promotes differentiation of the
      precursors into mature melanocytes. Our results support a model in which BMP4
      induces MITF expression in pluripotent stem cells and EDN3 subsequently promotes
      differentiation of these MITF expressing cells along the melanocyte lineage.

PMID- 24080015
TI  - Endotoxemia due to propofol contamination in four consecutive patients.

PMID- 24080014
TI  - Serine-204 in the linker region of Smad3 mediates the collagen-I response to TGF
      beta in a cell phenotype-specific manner.
AB  - Regulation of TGF-beta1/Smad3 signaling in fibrogenesis is complex. Previous work
      by our lab suggests that ERK MAP kinase phosphorylates the linker region (LR) of
      Smad3 to enhance TGF-beta-induced collagen-I accumulation. However the roles of
      the individual Smad3LR phosphorylation sites (T179, S204, S208 and S213) in the
      collagen-I response to TGF-beta are not clear. To address this issue, we tested
      the ability of Smad3 constructs expressing wild-type Smad3 or Smad3 with mutated
      LR phosphorylation sites to reconstitute TGF-beta-stimulated COL1A2 promoter
      activity in Smad3-null or -knockdown cells. Blocking ERK in fibroblasts and renal
      mesangial cells inhibited both S204 phosphorylation and Smad3-mediated COL1A2
      promoter activity. Mutations replacing serine at S204 or S208 in the linker
      region decreased Smad3-mediated COL1A2 promoter activity, whereas mutating T179
      enhanced basal COL1A2 promoter activity and did not prevent TGF-beta stimulation.
      Interestingly, mutation of all four Smad3LR sites (T179, S204, S208 and S213) was
      not inhibitory, suggesting primacy of the two inhibitory sites. These results
      suggest that in these mesenchymal cells, phosphorylation of the T179 and possibly
      S213 sites may act as a brake on the signal, whereas S204 phosphorylation by ERK
      in some manner releases that brake. Renal epithelial cells (HKC) respond
      differently from MEF or mesangial cells; blocking ERK neither changed TGF-beta
      stimulated S204 phosphorylation nor prevented Smad3-mediated COL1A2 promoter
      activity in HKC. Furthermore, re-expression of wild type-Smad3 or the S204A-Smad3
      mutant in Smad3-knockdown HKC reconstituted Smad3-mediated COL1A2 promoter
      activity. Collectively, these data suggest that Serine-204 phosphorylation in the
      Smad3LR is a critical event by which ERK enhances Smad3-mediated COL1A2 promoter
      activity in mesenchymal cells.

PMID- 24080016
TI  - Human pulmonary dirofilariasis coexisting with intercostal neurilemmoma: a case
      report and literature review.
AB  - Human pulmonary dirofilariasis (HPD) is a rare zoonotic infection caused by
      Dirofilaria immitis. Dogs are the definite hosts and humans are infected
      occasionally via a vector, generally a mosquito. Most thoracic neurilemmoma arise
      in the mediastinum and fewer tumors originate peripherally from the intercostal
      nerves. Most patients with HPD or thoracic neurilemmoma are asymptomatic and
      these diseases are often discovered incidentally. We present a 53-year-old female
      who was found to have a pulmonary nodule and a chest wall nodule during a routine
      health examination. She underwent a video-assisted thoracoscopic surgery (VATS)
      with partial lung resection and local excision of the chest wall. The
      pathological examination revealed a coiled, degenerating Dirofilariasis immitis
      worm surrounded by granulomatous inflammation with caseous necrosis and a
      neurilemmoma composed of S-100 protein immunoreactive but smooth muscle actin
      negative spindle cells. Because these diseases are self-limiting and make further
      treatment unnecessary, video-assisted thoracoscopic surgery (VATS) is considered
      preferable and less invasive for definitive diagnosis and management. 

PMID- 24080017
TI  - Copper doped hollow structured manganese oxide mesocrystals with controlled phase
      structure and morphology as anode materials for lithium ion battery with improved
      electrochemical performance.
AB  - We develop a facile synthesis route to prepare Cu doped hollow structured
      manganese oxide mesocrystals with controlled phase structure and morphology using
      manganese carbonate as the reactant template. It is shown that Cu dopant is
      homogeneously distributed among the hollow manganese oxide microspherical
      samples, and it is embedded in the lattice of manganese oxide by substituting
      Mn(3+) in the presence of Cu(2+). The crystal structure of manganese oxide
      products can be modulated to bixbyite Mn2O3 and tetragonal Mn3O4 in the presence
      of annealing gas of air and nitrogen, respectively. The incorporation of Cu into
      Mn2O3 and Mn3O4 induces a great microstructure evolution from core-shell
      structure for pure Mn2O3 and Mn3O4 samples to hollow porous spherical Cu-doped
      Mn2O3 and Mn3O4 samples with a larger surface area, respectively. The Cu-doped
      hollow spherical Mn2O3 sample displays a higher specific capacity of 642 mAhg(-1)
      at a current density of 100 mA g(-1) after 100 cycles, which is about 1.78 times
      improvement compared to that of 361 mA h g(-1) for the pure Mn2O3 sample,
      displaying a Coulombic efficiency of up to 99.5%. The great enhancement of the
      electrochemical lithium storage performance can be attributed to the improvement
      of the electronic conductivity and lithium diffusivity of electrodes. The present
      results have verified the ability of Cu doping to improve electrochemical lithium
      storage performances of manganese oxides.

PMID- 24080018
TI  - High-quality multiterminal suspended graphene devices.
AB  - We introduce a new scheme to realize suspended, multiterminal graphene structures
      that can be current annealed successfully to obtain uniform, very high quality
      devices. A key aspect is that the bulky metallic contacts are not connected
      directly to the part of graphene probed by transport measurements, but only
      through etched constriction, which prevents the contacts from acting invasively.
      The device high quality and uniformity is demonstrated by a reproducibly narrow
      (deltan ~ 10(9) cm(-2)) resistance peak around charge neutrality, by carrier
      mobility values exceeding 10(6) cm(2) V(-1) s(-1), by the observation of integer
      quantum Hall plateaus starting at 30 mT and of symmetry broken states at about
      200 mT, and by the occurrence of a negative multiterminal resistance directly
      proving the occurrence of ballistic transport. As these multiterminal devices
      enable measurements that cannot be done in a simpler two-terminal configuration,
      we anticipate that their use in future studies of graphene-based systems will be
      particularly relevant.

PMID- 24080019
TI  - Electrophysiological evidence of atypical processing underlying mental set
      shifting in ecstasy polydrug and polydrug users.
AB  - Executive functioning deficits are reported in ecstasy users. However research
      into mental set switching has been equivocal, with behavioral studies suggesting
      the function is preserved. The current study sought to address the issue of
      switching deficits in ecstasy users by combining behavioral performance with
      electrophysiological correlates (electroencephalography; EEG). Twenty ecstasy
      polydrug users, 20 nonecstasy polydrug users, and 20 drug naive controls were
      recruited. Participants completed questionnaires about their drug use, sleep
      quality, fluid intelligence, and current mood state. Each participant completed a
      mental set switching task (the number-letter task) while EEG measures were
      recorded. Analysis of variance (ANOVA) revealed no between-group differences on
      performance of the task; however a regression suggested that ecstasy use was a
      significant predictor for performance, after controlling for cannabis use. Mixed
      ANOVA revealed a significant effect of group on the P3, with significant
      differences between both drug groups and naives. There was also an interaction
      between electrode and group on the P2 component, with ecstasy users differing
      from both other groups. On the P3 component the results suggest a reduction in
      positivity at parieto-occipital electrodes for drug users compared to controls.
      Furthermore a significant increase in negativity in ecstasy users compared to
      control groups could be observed in several occipito-parietal electrodes at an N2
      component as well as observable atypicalities in early processing (P2) displayed
      by ecstasy users and polydrug controls. The present study provides evidence of
      atypical processing of attentional shifting in ecstasy and polydrug users.
      Deficits in this executive function could reflect cognitive inflexibility and
      paucity of rapid behavioral adjustment, which may be problematic in real world
      situations.

PMID- 24080020
TI  - Contingency management improves outcomes in cocaine-dependent outpatients with
      depressive symptoms.
AB  - Despite depressive symptoms being very common among patients seeking treatment
      for cocaine dependence, few studies have examined the effects of depressive
      symptoms on cocaine outpatient treatment outcomes, and there is even less
      research in the context of Contingency Management (CM). The purpose of this study
      was to assess the main and interactive effects of co-occurring depressive
      symptoms on CM outcomes. Cocaine-dependent individuals (N = 108) were randomized
      to Community Reinforcement Approach (CRA) or CRA plus CM in two outpatient
      community clinical settings. Participants were categorized according to
      depression symptoms, self-reported by means of the BDI at treatment entry.
      Outcome measures included treatment retention and documented cocaine abstinence
      over a 6-month treatment period. Depressive symptoms were more commonly found in
      females and in unemployed participants, and were associated with more drug
      related, social, and psychiatric problems at treatment entry. Individuals with
      baseline depressive symptoms had poorer treatment outcomes than patients without
      depressive symptoms. The addition of CM to CRA made the program more effective
      than with CRA alone, regardless of depressive symptoms. CM was associated with
      better abstinence treatment outcomes, while the interaction between unemployment
      and depressive symptoms was associated with negative retention treatment
      outcomes. This study supports the efficacy of CM for cocaine-dependent
      outpatients with and without depressive symptoms, and highlights its importance
      for improving treatment for unemployed and depressed cocaine-dependent
      individuals.

PMID- 24080021
TI  - A pilot study of pain-related anxiety and smoking-dependence motives among
      persons with chronic pain.
AB  - Complex interactions between pain and tobacco smoking have been of increasing
      interest to researchers and clinicians from a variety of disciplines. There is
      also recent evidence to suggest that pain-related anxiety may play an important
      role in the maintenance of tobacco dependence among persons with comorbid pain
      disorders. The goal of the current study was to evaluate the explanatory
      relevance of pain-related anxiety in relation to tobacco dependence among a
      sample of daily smokers with current chronic pain. Participants were recruited
      from the general population to complete an online survey that was developed to
      examine interrelations between chronic pain and tobacco smoking. Fifty-six of 129
      (43%) daily smoking respondents met criteria for current chronic pain. Results
      indicated that pain-related anxiety accounted for a significant portion of the
      unique variance in total smoking dependence scores, and both primary and
      secondary dependence composite scores (as measured by the Wisconsin Inventory of
      Smoking Dependence Motives; Piper et al., 2004). It is noteworthy that these
      effects were observed above and beyond the variance accounted for by relevant
      sociodemographic factors, generalized anxiety, and pain severity. Pain-related
      anxiety was observed to be strongly associated with secondary dependence motives,
      which is consistent with a conceptualization of pain-related anxiety as an
      instrumental or situational motivator of smoking. These results suggest that
      tobacco smokers with comorbid pain disorders may be at risk for maintaining or
      exacerbating their dependence on tobacco, possibly due to individual differences
      in pain-related anxiety. These findings may help inform the development of
      tailored interventions for smokers with comorbid chronic pain.

PMID- 24080022
TI  - Increased prevalence of autoimmune phenomena in myelofibrosis: relationship with
      clinical and morphological characteristics, and with immunoregulatory cytokine
      patterns.
AB  - Autoimmune phenomena and cytokines were investigated in 100 patients with
      myelofibrosis (MF) and related to marrow fibrosis and clinical risk. Anti
      erythrocyte antibodies by mitogen-stimulated direct antiglobulin test (MS-DAT)
      were positive in 45%, anti-platelets in 15% and organ/non organ-specific in 57%
      of cases, without clinically overt disease, and mostly in low-risk/intermediate
      risk-1 and MF-0/MF-1. TGF-beta and IL-8 were increased in MS-DAT positive cases,
      and IFN-gamma in patients with serological autoantibodies. TGF-beta and IL-17
      were elevated in early clinical and morphological stages, while IL-8 increased in
      advanced stages. These data suggest that autoimmune phenomena and cytokine
      disregulation are particularly relevant in early MF. 

PMID- 24080023
TI  - Small molecules are natural triggers for the disassembly of biofilms.
AB  - Gigantic bacterial communities, termed biofilms, thrive in a variety of
      situations. Held together by a protective matrix, a biofilm is a bacterial
      fortress whose inhabitants are much better protected against environmental
      insults than free-living bacteria. However, knowing how single bacteria can break
      away from the community could be harnessed to break up biofilms that form on
      prosthetic devices implanted into the human body. This review demonstrates how
      small secreted molecules can elegantly mediate the disassembly of biofilms. Four
      different mechanisms for natural triggers of disassembly are highlighted: signals
      and cues, cell envelope-modifying molecules, anti-matrix molecules, and molecules
      that promote cell death. 

PMID- 24080024
TI  - The speed of blood pressure fluctuations in patients with chronic obstructive
      pulmonary disease.
AB  - BACKGROUND: Chronic obstructive pulmonary disease (COPD) has been associated with
      increased risk for cardiovascular disease but mechanisms underlying this
      association are incompletely understood. The speed of beat-to-beat changes in
      systolic blood pressure (vSBP) was found to be pronounced in patients with
      elevated cardiovascular risk. Although increased vSBP may thus be a contributing
      mechanism to cardiovascular morbidity, no data exist on vSBP in patients with
      COPD. Therefore, the purpose of this study was to evaluate whether there is an
      association between severity of COPD and vSBP. METHODS: Resting beat-to-beat
      blood pressure was recorded during 5 min. vSBP was assessed by calculating the
      slopes of oscillatory fluctuations in SBP for different inter-beat intervals
      (IBI). Univariate and multivariate analyses were performed to evaluate the
      association between forced expiratory volume in 1 s (FEV1) and vSBP. RESULTS:
      This study comprised 60 patients with COPD (24 females) with a mean [SD] FEV1 of
      45.4 [22.7] %predicted and 34 healthy controls. Short-term fluctuations in SBP
      were more pronounced in patients with COPD compared to healthy controls. There
      was a significant inverse correlation between FEV1 and vSBP (r=-0.41, p=0.001).
      Even after adjustment for covariates in multivariate analysis, FEV1 was found to
      be independently associated with vSBP. CONCLUSIONS: Patients with COPD are
      characterised by steeper blood pressure changes than healthy controls. The speed
      of fluctuations in SBP is associated with the severity of airflow limitation.
      Increased vSBP may be a mechanism underpinning the association between COPD and
      cardiovascular disease.

PMID- 24080026
TI  - Peri-substituted (ace)naphthylphosphinoboranes. (Frustrated) Lewis pairs.
AB  - The synthesis and molecular structures of 1-(diphenylphosphino)-8
      naphthyldimesitylborane (1) and 5-(diphenylphosphino)-6
      acenaphthyldimesitylborane (2) are reported. The experimentally determined P-B
      peri distances of 2.162(2) and 3.050(3) A allow 1 and 2 to be classified as
      regular and frustrated Lewis pairs. The electronic characteristics of the
      (non)bonding P-B contacts are determined by analysis of a set of real-space
      bonding indicators (RSBIs) derived from the theoretically calculated electron and
      pair densities. These densities are analyzed utilizing the atoms-in-molecules
      (AIM), stockholder, and electron-localizability-indicator (ELI-D) space
      partitioning schemes. The recently introduced mapping of the electron
      localizability on the ELI-D basin surfaces is also applied. All RSBIs clearly
      discriminate the bonding P-B contact in 1 from the nonbonding P-B contact in 2,
      which is due to the fact that the acenaphthene framework is rather rigid, whereas
      the naphthyl framework shows sufficient conformational flexibility, allowing
      shorter peri interations. The results are compared to the previously known
      prototypical phosphinoborane Ph3PB(C6F5)3, which serves as a reference for a
      bonding P-B interaction. The most prominent features of the nonbonding P-B
      contact in 2 are the lack of an AIM bond critical point, the unaffected Hirshfeld
      surfaces of the P and B atomic fragments, and the negligible penetration of the
      electron population of the ELI-D lone pair basin of the P atom into the AIM B
      atomic basin. 

PMID- 24080025
TI  - Evidence for a surface confined ion-to-electron transduction reaction in solid
      contact ion-selective electrodes based on poly(3-octylthiophene).
AB  - The ion-to-electron transduction reaction mechanism at the buried interface of
      the electrosynthesized poly(3-octylthiophene) (POT) solid-contact (SC) ion
      selective electrode (ISE) polymeric membrane has been studied using synchrotron
      radiation-X-ray photoelectron spectroscopy (SR-XPS), near edge X-ray absorption
      fine structure (NEXAFS), and electrochemical impedance spectroscopy (EIS)/neutron
      reflectometry (NR). The tetrakis[3,5-bis(triflouromethyl)phenyl]borate (TFPB(-))
      membrane dopant in the polymer ISE was transferred from the polymeric membrane to
      the outer surface layer of the SC on oxidation of POT but did not migrate further
      into the oxidized POT SC. The TFPB(-) and oxidized POT species could only be
      detected at the outer surface layer (<=14 A) of the SC material, even after
      oxidation of the electropolymerized POT SC for an hour at high anodic potential
      demonstrating that the ion-to-electron transduction reaction is a surface
      confined process. Accordingly, this study provides the first direct structural
      evidence of ion-to-electron transduction in the electropolymerized POT SC ISE by
      proving TFPB(-) transport from the polymeric ISE membrane to the oxidized POT SC
      at the buried interface of the SC ISE. It is inferred that the performance of the
      POT SC ISE is independent of the thickness of the POT SC but is instead
      contingent on the POT SC surface reactivity and/or electrical capacitance of the
      POT SC. In particular, the results suggest that the electropolymerized POT
      conducting polymer may spontaneously form a mixed surface/bulk oxidation state,
      which may explain the unusually high potential stability of the resulting ISE. It
      is anticipated that this new understanding of ion-to-electron transduction with
      electropolymerized POT SC ISEs will enable the development of new and improved
      devices with enhanced analytical performance attributes. 

PMID- 24080028
TI  - Inconsistency of residents' communication performance in challenging
      consultations.
AB  - OBJECTIVE: Communication performance inconsistency between consultations is
      usually regarded as a measurement error that jeopardizes the reliability of
      assessments. However, inconsistency is an important phenomenon, since it
      indicates that physicians' communication may be below standard in some
      consultations. METHODS: Fifty residents performed two challenging consultations.
      Residents' communication competency was assessed with the CELI instrument.
      Residents' background in communication skills training (CST) was also
      established. We used multilevel analysis to explore communication performance
      inconsistency between the two consultations. We also established the
      relationships between inconsistency and average performance quality, the type of
      consultation, and CST background. RESULTS: Inconsistency accounted for 45.5% of
      variance in residents' communication performance. Inconsistency was dependent on
      the type of consultation. The effect of CST background training on performance
      quality was case specific. Inconsistency and average performance quality were
      related for those consultation combinations dissimilar in goals, structure, and
      required skills. CST background had no effect on inconsistency. CONCLUSION:
      Physician communication performance should be of high quality, but also
      consistent regardless of the type and complexity of the consultation. PRACTICE
      IMPLICATIONS: In order to improve performance quality and reduce performance
      inconsistency, communication education should offer ample opportunities to
      practice a wide variety of challenging consultations.

PMID- 24080027
TI  - Adherence to human lung microvascular endothelial cells (HMVEC-L) of Plasmodium
      vivax isolates from Colombia.
AB  - BACKGROUND: For years Plasmodium vivax has been considered the cause of benign
      malaria. Nevertheless, it has been observed that this parasite can produce a
      severe disease comparable to Plasmodium falciparum. It has been suggested that
      some physiopathogenic processes might be shared by these two species, such as
      cytoadherence. Recently, it has been demonstrated that P. vivax-infected
      erythrocytes (Pv-iEs) have the capacity to adhere to endothelial cells, in which
      intercellular adhesion molecule-1 (ICAM-1) seems to be involved in this process.
      METHODS: Adherence capacity of 21 Colombian isolates, from patients with P. vivax
      mono-infection to a microvascular line of human lung endothelium (HMVEC-L) was
      assessed in static conditions and binding was evaluated at basal levels or in
      tumor necrosis factor (TNF) stimulated cells. The adherence specificity for the
      ICAM-1 receptor was determined through inhibition with an anti-CD54 monoclonal
      antibody. RESULTS: The majority of P. vivax isolates, 13 out of 21 (61.9%),
      adhered to the HMVEC-L cells, but P. vivax adherence was at least seven times
      lower when compared to the four P. falciparum isolates. Moreover, HMVEC-L
      stimulation with TNF led to an increase of 1.6-fold in P. vivax cytoadhesion,
      similar to P. falciparum isolates (1.8-fold) at comparable conditions. Also,
      blockage of ICAM-1 receptor with specific antibodies showed a significant 50%
      adherence reduction. CONCLUSIONS: Plasmodium vivax isolates found in Colombia are
      also capable of adhering specifically in vitro to lung endothelial cells, via
      ICAM-1 cell receptor, both at basal state and after cell stimulation with TNF.
      Collectively, these findings reinforce the concept of cytoadherence for P. vivax,
      but here, to a different endothelial cell line and using geographical distinct
      isolates, thus contributing to understanding P. vivax biology.

PMID- 24080029
TI  - Macrophages: supportive cells for tissue repair and regeneration.
AB  - Macrophages, and more broadly inflammation, have been considered for a long time
      as bad markers of tissue homeostasis. However, if it is indisputable that
      macrophages are associated with many diseases in a deleterious way, new roles
      have emerged, showing beneficial properties of macrophages during tissue repair
      and regeneration. This discrepancy is likely due to the high plasticity of
      macrophages, which may exhibit a wide range of phenotypes and functions depending
      on their environment. Therefore, regardless of their role in immunity,
      macrophages play a myriad of roles in the maintenance and recovery of tissue
      homeostasis. They take a major part in the resolution of inflammation. They also
      exert various effects of parenchymal cells, including stem and progenitor cell,
      of which they regulate the fate. In the present review, few examples from various
      tissues are presented to illustrate that, beyond their specific properties in a
      given tissue, common features have been described that sustain a role of
      macrophages in the recovery and maintenance of tissue homeostasis. 

PMID- 24080030
TI  - Proteolytic activity of Plasmodium falciparum subtilisin-like protease 3 on
      parasite profilin, a multifunctional protein.
AB  - Subtilisin-like proteases of malaria parasite Plasmodium falciparum (PfSUB1, 2
      and 3) are expressed at late asexual blood stages. PfSUB1 and 2 are considered
      important drug targets due to their essentiality for parasite blood stages and
      role in merozoite egress and invasion of erythrocytes. We have earlier shown the
      in vitro serine protease activity of PfSUB3 and its localization at asexual blood
      stages. In this study, we attempted to identify the biological substrate(s) of
      PfSUB3 and found parasite profilin (PfPRF) as a substrate of the protease.
      Eukaryotic profilins are multifunctional proteins with primary role in regulation
      of actin filament assembly. PfPRF possesses biochemical features of eukaryotic
      profilins and its rodent ortholog is essential in blood stages. Profilin from
      related apicomplexan parasite Toxoplasma gondii (TgPRF) is known to be involved
      in parasite motility, host cell invasion, active egress from host cell, immune
      evasion and virulence in mice. In this study, mature PfSUB3 proteolysed
      recombinant PfPRF in a dose-dependent manner in in vitro assays. Recombinant
      PfPRF was assessed for its proinflammatory activity and found to induce high
      level of TNF-alpha and low but significant level of IL-12 from mouse bone marrow
      derived dendritic cells. Proteolysis of PfPRF by PfSUB3 is suggestive of the
      probable role of the protease in the processes of motility, virulence and immune
      evasion. 

PMID- 24080031
TI  - Kinetoplastid-specific histone variant functions are conserved in Leishmania
      major.
AB  - Regions of transcription initiation and termination in kinetoplastid protists
      lack known eukaryotic promoter and terminator elements, although epigenetic marks
      such as histone variants and the modified DNA base J have been localized to these
      regions in Trypanosoma brucei, Trypanosoma cruzi, and/or Leishmania major.
      Phenotypes of base J mutants vary significantly across trypanosomatids, implying
      divergence in the epigenetic networks governing transcription during evolution.
      Here, we demonstrate that the histone variants H2A.Z and H2B.V are essential in
      L. major using a powerful quantitative plasmid segregation-based test. In
      contrast, H3.V is not essential for viability or normal growth in Leishmania.
      Steady-state transcript levels and the efficiency of transcription termination at
      convergent strand switch regions (SSRs) in H3V-null parasites were comparable to
      WT parasites. Our genetic tests show a conservation of histone variant phenotypes
      between L. major and T. brucei, unlike the diversity of phenotypes associated
      with genetic manipulation of the DNA base J modification. 

PMID- 24080032
TI  - Combined antihypertensive effect of luteolin and buddleoside enriched extracts in
      spontaneously hypertensive rats.
AB  - ETHNOPHARMACOLOGICAL RELEVANCE: Flos Chrysanthemi is used in a variety of
      diseases in traditional Chinese medicine including hypertension, and the total
      flavonoids (rich in luteolin (LUT) and buddleoside (BUD)) of Flos Chrysanthemi is
      known to modulate vascular functions and reduce the blood pressure. However, the
      active flavonoids and their synergistic effects on anti-hypertension are still
      unclear. To investigate the combined anti-hypertension effects of LUT and BUD
      enriched extracts on spontaneously hypertensive rats (SHR), as well as the anti
      hypertensive mechanism of LUT&BUD mixture. MATERIALS AND METHODS: CODA Mouse &
      Rat Tail-Cuff Blood Pressure System was used to measure the systolic blood
      pressure (SBP) and diastolic blood pressure (DBP) of SHR after treated with
      extracts contains with LUT and/or BUD. The expressions of Ang II, PRA, ALD, ET,
      PGI2 and TXB2 were investigated by ELASA. Serum NO concentration was measured by
      the method of Nitric acid reductase. RESULTS: A single administration of LUT,
      BUD, or LUT:BUD=1:1 significantly reduced SBP by about 3.35 mmHg, 4.39 mmHg and
      15.42 mmHg, respectively. Chronic administration of LBM (at 60 mg/kg; p.o. for 30
      days) reduced both SBP and DBP by 4.04% and 5.24% of the vehicle group,
      respectively. Oral administration of LBM at 60 mg/kg inhibited the serum levels
      of ANG, ALD and ET, but increased serum NO concentration. CONCLUSION: This study
      shows the synergistic anti-hypertension effects of LUT and BUD in SHR. The
      effects of LBM on blood pressure are associated with RAAS and endothelial system.
      Thus, our experiments suggest that the combination of luteolin and buddleoside
      from Flos Chrysanthemi are potentially useful for the therapeutic treatments for
      hypertension.

PMID- 24080033
TI  - Caspase-mediated cleavage and DNase activity of the translation initiation factor
      3, subunit G (eIF3g).
AB  - Eukaryotic translation initiation factor 3 is composed of 13 subunits (eIF3a
      through eIF3m) and plays an essential role in translation. During apoptosis,
      several caspases rapidly down-regulate protein synthesis by cleaving eIF4G, -4B, 
      3j, and -2alpha. In this study, we found that the activation of caspases by
      cisplatin in T24 cells induces the cleavage of subunit G of the eIF3 complex
      (eIF3g). The cleavage site (SLRD(220)G) was identified, and we found that the
      cleaved N-terminus was translocated to the nucleus, activating caspase-3, and
      that it also showed a strong DNase activity. These data demonstrate the important
      roles of eIF3g in the translation initiation machinery and in DNA degradation
      during apoptosis. 

PMID- 24080034
TI  - [Support for parental caregivers in pediatrics].

PMID- 24080035
TI  - [A strange migrating hair].

PMID- 24080036
TI  - [Diffuse pulmonary lymphangiomatosis in a child].

PMID- 24080039
TI  - [Vitamin-responsive epilepsies: an update].
AB  - Inborn error of metabolism may produce a complex clinical picture in which
      epilepsy is only one of the various neurologic manifestations including
      developmental delay/regression, mental retardation, and movement disorders.
      However, metabolic epilepsies may dominate the clinical presentation. A specific
      diagnosis of metabolic disorders in epileptic patients may provide the
      possibility of specific treatments that can improve seizures. In a few metabolic
      diseases such as vitamin-responsive epilepsies, epilepsy responds to specific
      treatments based on supplementation of cofactors. Certain rare vitamin-responsive
      inborn errors of metabolism may present as early encephalopathy with
      anticonvulsant-resistant seizures. These include pyridoxine-dependent seizures,
      pyridoxal-phosphate-dependent seizures, folinic acid-responsive seizures, and
      biotinidase deficiency. This review discusses our current understanding of these
      vitamin-responsive epilepsies. 

PMID- 24080040
TI  - [A survey of milk reintroduction in children with cow milk protein allergy in
      pediatric departments of French hospitals].
AB  - The outcome of cow milk allergy (CMA) usually progresses to acquisition of
      tolerance, allowing a normal diet. This study conducted in France aimed to survey
      practices of milk reintroduction after an exclusion diet. A questionnaire was
      sent to 278 pediatric centers, exploring the reintroduction procedure in the 3
      main types of CMA and in patients with persistent allergy. The response rate was
      27%, 53% for tertiary centers and 23% for secondary centers. Cow's milk is
      reintroduced at a median age of 12months, and after 6months of exclusion diet
      whatever the type of allergy. In about half the centers, Prick-Tests and specific
      IgE are tested before milk reintroduction, but the procedure in case of a
      positive test differs between centers. Procedures are similar regarding the type
      of milk, the quantity, the place (home or hospital), the presence of an
      intravenous line, and the time before a second reintroduction. A desensitization
      procedure is proposed in 43% of centers in case of persistent allergy, after 2
      reintroduction failures, and at a median age of 2.5years. Milk reintroduction
      procedures are similar to those for oral challenge for the diagnosis of CMA but
      with differences between centers. 

PMID- 24080041
TI  - Bioinspired multifunctional hetero-hierarchical micro/nanostructure tetragonal
      array with self-cleaning, anticorrosion, and concentrators for the SERS
      detection.
AB  - Heterohierarchical micro/nanostructure tetragonal array consisted of engineering
      materials of microprotrusion-like Cu and secondary nanostructured dendrite Ag
      have been fabricated via a primary cell-induced deposition and a facile galvanic
      displacement reaction combined with photolithography technique on Cu foil.
      Confined by the circle microwell tetragonal array of the photoresist template,
      regular microprotrusion-like Cu with the tunable size of diameter can be easily
      deposited on the surface of Cu foil. Then, the secondary dendritic Ag
      nanostructures in situ grow on the surface of microprotrusion via a galvanic
      displacement reaction, leading to the formation of heterohierarchical
      micro/nanostructure tetragonal array, which is similar to the surface
      microstructure of the lotus leaf. Inspired by this novel surface structure of
      imitating lotus leaf, its wettability has been systematically investigated. The
      results indicate that the fabricated heterohierarchical micro/nanostructure
      regular array after the surface fluoration presents a remarkable superhydrophobic
      performance. Initiated from its superhydrophobicity, an excellent self-cleaning
      property has also been demonstrated. In addition, the durability of the
      superhydrophobic surfaces is examined in the wide pH range of corrosive liquids.
      Notably, the fabricated superhydrophobic surface can be potentially used as
      concentrators, which presents a great perspective in the field of analysis
      through employing the SERS detection as an example. 

PMID- 24080042
TI  - Exxon Valdez to Deepwater Horizon: comparable toxicity of both crude oils to fish
      early life stages.
AB  - The 2010 Deepwater Horizon disaster in the Gulf of Mexico was the largest oil
      spill in United States history. Crude oils are highly toxic to developing fish
      embryos, and many pelagic fish species were spawning in the northern Gulf in the
      months before containment of the damaged Mississippi Canyon 252 (MC252) wellhead
      (April-July). The largest prior U.S. spill was the 1989 grounding of the Exxon
      Valdez that released 11 million gallons of Alaska North Slope crude oil (ANSCO)
      into Prince William Sound. Numerous studies in the aftermath of the Exxon Valdez
      spill defined a conventional crude oil injury phenotype in fish early life
      stages, mediated primarily by toxicity to the developing heart. To determine
      whether this type of injury extends to fishes exposed to crude oil from the
      Deepwater Horizon - MC252 incident, we used zebrafish to compare the
      embryotoxicity of ANSCO alongside unweathered and weathered MC252 oil. We also
      developed a standardized protocol for generating dispersed oil water-accommodated
      fractions containing microdroplets of crude oil in the size range of those
      detected in subsurface plumes in the Gulf. We show here that MC252 oil and ANSCO
      cause similar cardiotoxicity and photo-induced toxicity in zebrafish embryos.
      Morphological defects and patterns of cytochrome P450 induction were largely
      indistinguishable and generally correlated with polycyclic aromatic compound
      (PAC) composition of each oil type. Analyses of embryos exposed during different
      developmental windows provided additional insight into mechanisms of crude oil
      cardiotoxicity. These findings indicate that the impacts of MC252 crude oil on
      fish embryos and larvae are consistent with the canonical ANSCO cardiac injury
      phenotype. For those marine fish species that spawned in the northern Gulf of
      Mexico during and after the Deepwater Horizon incident, the established
      literature can therefore inform the assessment of natural resource injury in the
      form of potential year-class losses.

PMID- 24080043
TI  - Change fatigue in clinical practice.

PMID- 24080044
TI  - Altruism--a coping mechanism for patients on clinical trials: a nursing
      perspective.
AB  - Altruism often is expressed by patients with advanced cancer as a coping
      mechanism and a motivational factor for participation in clinical trials. Those
      who participate develop a sense of hope that their life is a contribution, which
      may continue to live beyond their deaths. 

PMID- 24080045
TI  - Standardization of initial chemotherapy teaching to improve care.
AB  - Recognizing that each nurse approaches patient education differently, a team of
      nurses at Dana-Farber Cancer Institute satellite facilities employed quality
      improvement strategies to develop a standardized approach to patient education.
      The goal was to eliminate variation in teaching and improve patient satisfaction
      scores. 

PMID- 24080046
TI  - Using a simple diary for management of nausea and vomiting during chemotherapy.
AB  - To help clinical staff make effective adjustments to patients' antiemetic
      therapy, the authors gave patients a nausea and vomiting diary to record their
      experiences. Use of the diary strengthened patients' sense of security, as well
      as trust between staff and patients, in addition to increasing the staff's
      sensitivity to cultural differences in their approach to cancer and chemotherapy.
      Most patients responded favorably to the opportunity to express their fears and
      anxieties in diary format. 

PMID- 24080047
TI  - Therapeutic misconceptions and misestimations in oncology: a clinical trial
      nurse's guide.
AB  - Therapeutic misconceptions and misestimations occur frequently in oncology
      clinical trials and can potentially compromise informed consent. Despite the
      increased awareness of these issues in medical literature, many practitioners and
      nurses continue to be unfamiliar with these concepts. This article will define
      therapeutic misconceptions and misestimations, explore contributing factors, and
      explain how they can be prevented by clinical trial nurses. 

PMID- 24080048
TI  - Drug shortages and the burden of access to care: a critical issue affecting
      patients with cancer.
AB  - Pharmaceutical drug shortages are multifaceted and complex problems that affect
      all aspects of health care, including patients, caregivers, healthcare providers,
      third-party payers, the pharmaceutical industry, and regulators. Drug shortages
      have increased significantly since 2000, which cause increases in healthcare
      costs and compromised patient care. New government regulations have led the U.S.
      Food and Drug Administration to focus efforts on updating policies and improving
      regulation of the pharmaceutical industry to limit and avoid drug shortages. This
      article discusses the current issues surrounding the pharmaceutical drug shortage
      and the implications for patients and healthcare providers. A review of the
      literature presents the multidimensional impact of the pharmaceutical drug
      shortage, and the analysis shows patients who are most burdened by drug shortages
      and have experienced substandard care, increased cost of care, and compromised
      quality of health care. 

PMID- 24080049
TI  - The need for a nursing presence in oral chemotherapy.
AB  - As cancer treatment shifts from IV to oral chemotherapy, patients have less
      contact with nurses and face the increased responsibility of maintaining their
      own health care. The authors conducted focus group interviews with 18 oncology
      nurses using the grounded theory approach to explore the nurses' perceptions of
      current practices and ideas regarding opportunities to improve nursing practice
      for patients receiving oral chemotherapy. The nursing presence is becoming
      invisible and, therefore, these patients are isolated more in current practice.
      "The need for a nursing presence" emerged as a core category. Nurse involvement
      in patient entry into oral chemotherapy was perceived as important for
      identifying patients at risk for nonadherence. In their partnership with
      patients, nurses should be attentive, connect with patients, elicit patients'
      unmet needs, and provide committed patient support. Rather than the traditional
      reactive approach, proactive patient care is required. In addition, nurses are
      expected to coordinate patient care and facilitate interpersonal relationships
      among healthcare providers. Coordinated proactive care leads to predictive care
      to meet the future needs of patients, including the prevention of adverse events.
      The roles and responsibilities of nurses in oral chemotherapy must be clarified
      so that the nursing presence is clear to patients and other healthcare providers.

PMID- 24080050
TI  - Sleep interrupted: nocturnal care disturbances following hematopoietic stem cell
      transplantation.
AB  - Sleep is an essential biologic and physiologic process that is vital for
      maintaining or achieving optimal health outcomes. Care requirements in
      hospitalized patients frequently result in nocturnal disruptions that impact
      sleep quality. This exploratory, retrospective study aimed to identify and
      quantify nocturnal care disruptions in patients undergoing hematopoietic stem
      cell transplantation. A total of 1,642 nocturnal care interactions occurred
      during 160 patient nights of data collection. An average of 41 nocturnal care
      interactions occurred per patient. Most occurred from 12-12:59 am and 4-4:59 am.
      Most patients (73%) had sleep disturbance recorded in their chart by nurses, but
      physicians documented sleep disturbances for only 28% of patients. Care practices
      may be modifiable to promote sleep in the hospital setting. 

PMID- 24080051
TI  - Foundations for lung nodule management for nurse navigators.
AB  - Lung cancer remains the most deadly cancer, with more than half of patients dying
      within one year of diagnosis. However, mortality rates improve with early
      detection. Until recently, attempts at improving early detection of lung cancer
      have not been shown to be beneficial, but when results from the National Lung
      Screening Trial showed a survivor benefit for high-risk patients who had a
      computed tomography scan, interest grew rapidly in creating guidelines and
      programs that restructure lung nodule management and screening. Oncology nurse
      navigators will play a crucial role in the development and administration of
      tracking methods, data analysis, and program development that will contribute to
      the multidisciplinary team in screening, tracking, and diagnosing early-stage
      lung cancer. 

PMID- 24080052
TI  - Information for patients with or at risk of cancer-related lymphedema.
AB  - The Internet has great potential to provide information to patients with or at
      risk of developing cancer-related lymphedema (CRL), a complication of cancer
      treatment. To evaluate Web site structure (e.g., accreditation, design) and
      content (e.g., validity) for available Web sites on CRL, lymphedema, lymphoedema,
      cancer, and oncology were used with 10 search engines (five French and five
      English). The first page of each Web site was examined and the content was
      identified and classified using the evaluation model of the Science Panel on
      Interactive Communication and Health. The search strategy yielded 120 Web sites.
      Using inclusion and exclusion criteria, 19 Web sites were selected. The authors
      found that 79% of the Web sites focused exclusively on CRL and 74% were in
      English. Although information about each site's sponsor, goal, and target
      audience was readily available, content material was incomplete and evaluation of
      Web site impact and effectiveness was nonexistent. This review suggests that Web
      sites about CRL vary greatly in terms of structure and content. 

PMID- 24080053
TI  - Development of an evidence-based exercise and education cancer recovery program.
AB  - Cancer-related fatigue is one of the most common and distressing side effects
      experienced by patients with cancer. Increased activity and exercise have been
      shown to significantly impact cancer-related fatigue and are beneficial during
      and after treatment. This article describes the development and implementation of
      a 12-week evidence-based exercise and education program for cancer survivors in a
      community medical center. Participants consistently reported significant
      improvements in fatigue, depression, sleep disturbances, pain, and quality of
      life. The improvements were independent of the type of cancer, extent of disease,
      or treatment status. Additional benefits described by participants were support,
      a sense of belonging, and being understood. 

PMID- 24080054
TI  - The experience of implementing evidence-based practice change: a qualitative
      analysis.
AB  - The Oncology Nursing Society (ONS) and ONS Foundation worked together to develop
      the Institute for Evidence-Based Practice Change (IEBPC) program to facilitate
      the implementation of evidence-based practice (EBP) change in nursing. This
      analysis describes the experience of 19 teams of nurses from various healthcare
      settings who participated in the IEBPC program. Qualitative analysis of verbatim
      narratives of activities and observations during the process of implementing an
      EBP project was used to identify key themes in the experience. EBP implementation
      enabled participants to learn about their own practice and to experience
      empowerment through the evidence, and it ignited the spirit of inquiry, team
      work, and multidisciplinary collaboration. Experiences and lessons learned from
      nurses implementing EBP can be useful to others in planning EBP implementation. 

PMID- 24080055
TI  - Changes in breast radiotherapy: prone positioning and hypofractionation.
AB  - Breast cancer management has drastically changed since the 1990s. Many patients
      with breast cancer now can opt to conserve their breast through a lumpectomy and
      radiation (breast conservation therapy), rather than a full mastectomy. Advances
      in the techniques of delivery and length of breast radiotherapy have been rapidly
      evolving. This article attempts to summarize some of those changes for nurses
      caring for patients with breast cancer during radiation therapy. 

PMID- 24080056
TI  - Coadministration of 5% glucose solution and dexamethasone and oxaliplatin-related
      vascular pain grade: a case study.
AB  - Agents used in cancer treatment can cause many side effects in patients.
      Oxaliplatin is a platinum-based cytotoxic agent that is used in the treatment of
      colorectal cancers, and one of its potential side effects is vascular pain. The
      current article will discuss the coadministration of dexamethasone and its
      potential effect on oxaliplatin-related vascular pain. 

PMID- 24080057
TI  - A multidisciplinary team approach to improving psychosocial care in patients with
      cancer.
AB  - The demand for patient-centered care has reinforced the need for a systematic
      approach to planning appropriate psychosocial services. A proposed strategy to
      address this need is to use a multidisciplinary team comprised of oncology
      nurses, physicians, mental health professionals, social workers, ethicists, and
      other healthcare professionals to provide comprehensive psychosocial care to
      patients and their families. This article describes key aspects of a broad-based
      team approach used to develop evidence-based, multidisciplinary practice change
      that could improve psychosocial care and outcomes. 

PMID- 24080058
TI  - Exercise interventions on health-related quality of life for patients with cancer
      during active treatment.

PMID- 24080059
TI  - The mysterious effect of the quilt.
AB  - All of us have heard that a picture is worth a thousand words, yet the 25
      pictures on each of the quilts in our office often evoke awed silence. I want to
      tell you the story of our quilts. 

PMID- 24080060
TI  - Nursing perspectives on trastuzumab emtansine for the treatment of metastatic
      breast cancer.
AB  - Increased understanding of the molecular composition of breast cancer tumors has
      led to the development of targeted anticancer agents. Novel therapies directed
      against human epidermal growth factor receptor 2 (HER2) in breast cancer have
      been developed. One such agent, trastuzumab emtansine (T-DM1), is an antibody
      drug conjugate that has been shown to be effective in the treatment of women with
      HER2-positive breast cancer. Phase I and II studies have determined a maximum
      tolerated dose, and several phase Ib/II, II, and III studies have shown improved
      tolerability and efficacy compared with the combination of trastuzumab and
      chemotherapy. The most concerning grade 3 or higher adverse events associated
      with T-DM1 include thrombocytopenia and transaminitis. To ensure that these
      adverse events do not delay or interrupt treatment, oncology nurses need to
      familiarize themselves with these risks and their management. This article
      reviews the clinical development of T-DM1 and its usage, with a focus on the
      nurse's role in preventing and managing adverse events associated with T-DM1
      therapy. 

PMID- 24080061
TI  - Evidence-based guideline recommendations.
AB  - Cancer survivorship is expected to increase in coming years. Survivors include
      recipients of hematopoietic stem cell transplantations, signaling the necessity
      for evidence-based guidelines that focus on long-term follow-up needs. Studies
      have shown that evidence-based care can improve cancer survivors' quality of life
      and long-term outcomes. The implication is that early identification and
      intervention in chronic health problems such as graft-versus-host disease result
      in improved outcomes and a higher quality of survivorship. These discoveries
      signal a need to provide specific care management with appropriate and timely
      screening and preventive services. Recommendations for long-term follow-up post
      hematopoietic stem cell transplantation are an important guide to direct clinical
      practice with this patient population and optimize their outcomes. 

PMID- 24080062
TI  - A history in-care predicts unique characteristics in a homeless population with
      mental illness.
AB  - Multiple studies of homeless persons report an increased prevalence of a history
      in-care, but there is a dearth of information on associated outcomes or relevant
      demographic profiles. This information is critical to understanding if certain
      individuals are at elevated risk or might benefit from specific intervention.
      Here, we investigate how a history in-care relates to demographics and multiple
      outcome measures in a homeless population with mental illness. Using the Mini
      International Neuropsychiatric Interview (MINI), the Short-Form 12, and a trauma
      questionnaire, we investigated baseline differences in demographics and length of
      homelessness in the At Home/Chez Soi Trial (N=504) Winnipeg homeless population
      with and without a history in-care. Approximately 50% of the homeless sample
      reported a history in-care. This group was significantly more likely to be young,
      female, married or cohabitating, of Aboriginal heritage, have less education, and
      have longer lifetime homelessness. Individuals of Aboriginal heritage with a
      history in-care were significantly more likely to report a familial history of
      residential school. Individuals with a history in-care experienced different
      prevalence rates of Axis 1 mental disorders. Those with a history in-care also
      reported significantly more traumatic events (particularly interpersonal). A
      distinctive high-risk profile emerged for individuals with a history in-care.
      Sociocultural factors of colonization and intergenerational transmission of
      trauma appear to be particularly relevant in the trajectories for individuals of
      Aboriginal heritage. Given the high prevalence of a history in-care,
      interventions and policy should reflect the specific vulnerability of this
      population, particularly in regards to trauma-informed services. 

PMID- 24080063
TI  - Blastocystis: getting to grips with our guileful guest.
AB  - Blastocystis, a common single-celled intestinal parasite of humans and animals,
      continues to puzzle clinical microbiologists, gastroenterologists, and general
      practitioners who are still unsure of the clinical significance of the organism.
      Here we consider some less well-addressed areas of Blastocystis research, which,
      facilitated by recent technological advances, could potentially turn out to be
      significant pathways to knowledge. First and foremost we discuss new trends in
      Blastocystis research, including the 'omics' perspectives, and then highlight
      some aspects of Blastocystis research in the context of host coevolution, its
      potential as a biomarker of intestinal functionality, and its relationship to
      other components of the human intestinal microbiota. 

PMID- 24080064
TI  - Troglostrongylus brevior and a nonexistent 'dilemma'.

PMID- 24080065
TI  - In vitro photoacoustic visualization of myocardial ablation lesions.
AB  - BACKGROUND: Radiofrequency (RF) ablation to treat atrial arrhythmia is limited by
      the inability to reliably assess lesion durability and transmurality. OBJECTIVE:
      The purpose of this study was to determine the feasibility of photoacoustic
      characterization of myocardial ablation lesions in vitro. In this study, we
      investigated the feasibility of combined ultrasound (US) and spectroscopic
      photoacoustic imaging to visualize RF ablation lesions in three dimensions (3D)
      based on unique differences in the optical absorption spectra between normal and
      ablated myocardial tissue. METHODS: Tissue samples were excised from the
      ventricles of fresh porcine hearts. Lesions were generated using an RF catheter
      ablation system using 20 to 30 W of power applied for 40 to 60 seconds. Ablated
      samples were imaged in the near-infrared regime (740-780 nm) using a combined
      PA/US imaging system. Measured PA spectra were correlated to the absorption
      spectra of deoxyhemoglobin and ablated tissue to produce a tissue
      characterization map (TCM) identifying 3D lesion location and extent. Tissue
      samples were stained and photographed for gross pathology. TCM and gross
      pathology images were coregistered to assess TCM accuracy. RESULTS: TCM reliably
      characterized ablated and non-ablated tissue up to depths of 3 mm. TCM also
      assessed lesion position and extent with submillimeter accuracy in multiple
      dimensions. Segmented TCMs achieved >69% agreement with gross pathology.
      CONCLUSION: The study results suggest that spectroscopic photoacoustic imaging
      has the potential to accurately assess RF ablation lesion size and position with
      submillimeter precision and may be well suited to guide transcatheter RF atrial
      ablation in clinical practice.

PMID- 24080066
TI  - Seasonal variation in the frequency of sudden cardiac death and ventricular
      tachyarrhythmia in patients with arrhythmogenic right ventricular
      dysplasia/cardiomyopathy: the effect of meteorological factors.
AB  - BACKGROUND: Sudden cardiac death (SCD) is the most catastrophic presentation in
      patients with arrhythmogenic right ventricular dysplasia/cardiomyopathy (ARVD/C).
      OBJECTIVES: To investigate the seasonal variations in the frequency of SCD and
      ventricular tachyarrhythmia in patients with AVRD/C and to elucidate the
      meteorological factors that trigger these events. METHODS: From 1998 to 2012, we
      enrolled 88 consecutive patients with ARVD/C from Taipei City. The cohort
      included 20 living patients who received implantable cardioverter-defibrillator
      (ICD) and 68 autopsied patients with SCD from the Taiwan National Forensic
      Institute registry. The baseline clinical characteristics, seasonal distribution,
      and associated meteorological factors were explored to predict the occurrences of
      events, which include appropriate ICD interventions and SCD. RESULTS: There were
      106 events, including 38 (35.8%, 1.9 episodes per patient) appropriate ICD
      interventions in living patients with ARVD/C and 68 (64.2%) SCD events. The
      seasonal peak occurred predominantly in summer (P < .05) in both groups. For
      meteorological factors, the onset of event was associated with higher average
      daily temperature and longer sunshine duration. The variation in humidity within
      3 days of events was significantly increased. After multivariate logistic
      regression analysis, higher average daily temperature and larger variation in
      humidity were associated with increase in events (odds ratio 1.23, 95% confidence
      interval 1.16-1.31, P < .001, and odds ratio 1.19, 95% confidence interval 1.15
      1.23, P < .001, respectively). CONCLUSIONS: There was seasonal variation with a
      summer peak in the occurrence of ventricular arrhythmias and SCD in patients with
      ARVD/C. Meteorological factors including higher temperature and larger variation
      in humidity within 3 days of events were independently associated with the
      development of events.

PMID- 24080068
TI  - Chiari I malformation associated with atlanto-occipital assimilation presenting
      as orthopnea and cough syncope.
AB  - Although it is not uncommon for patients with Chiari I malformations to present
      with respiratory complaints, cough syncope is a rare presenting symptom. We
      report an adult patient who had both a Chiari I malformation and atlanto
      occipital assimilation, and complained of cough syncope, orthopnea, and central
      sleep apnea. The patient underwent decompressive craniectomy of the posterior
      fossa and a cervical level 2 laminectomy. However, due to an initial under
      appreciation of the profound narrowing of the foramen magnum as a result of these
      concomitant pathologies, the patient had continued impaired cerebrospinal fluid
      flow, leading to a symptomatic pseudomeningocele and required a more extensive
      decompression that included a cervical level 3 laminectomy as well as a temporary
      lumbar drain. On 2 year follow-up, he remained asymptomatic.

PMID- 24080067
TI  - Abnormal electroencephalograms in patients with long QT syndrome.
AB  - BACKGROUND: The long QT syndrome (LQTS) is an inherited cardiac channelopathy
      associated with syncope and sudden cardiac death due to ventricular arrhythmias.
      It is most frequently caused by potassium channel mutations. Potassium channels
      are also expressed in brain tissue and play an important role in idiopathic
      epilepsies. Recent reports have indicated that related potassium channel
      mutations may coexpress as concomitant epilepsy and LQTS. OBJECTIVE: The purpose
      of this study was to explore cerebral activity by means of EEG recordings in
      individuals with LQTS related to potassium channel mutations. METHODS: Seventeen
      individuals with confirmed LQTS related to potassium channel mutations (11 LQT1
      and 6 LQT2) were prospectively studied with 21-channel electroencephalography
      (EEG) LQTS -related symptoms, comorbidity, medication, and QTc (12-lead ECG) were
      recorded. Sixteen healthy individuals previously studied with EEG served as a
      control group. All EEGs were reviewed by two independent neurophysiologists.
      RESULTS: EEG recordings were abnormal in 12 of 17 patients (71%) in the LQTS
      group, whereas abnormalities were present in only 2 of 16 healthy controls (13%;
      P <.01). In the LQTS group, all abnormal EEGs showed a combination of theta
      activity and sharp waves. Two patients showed additional delta activity. None of
      the patients had definite epileptic activity (spikes, spike waves). CONCLUSION:
      Abnormal electrical cerebral activity was identified more frequently in subjects
      with LQTS secondary to a potassium channel mutation compared with healthy
      controls. This result indicates a possible link between cardiac and cerebral
      channelopathy.

PMID- 24080069
TI  - Maternal stress, well-being, and impaired sleep in mothers of children with
      developmental disabilities: a literature review.
AB  - Having children with developmental disabilities (DDs) requires a high level of
      caregiving responsibilities, and existing studies support that mothers of
      children with DDs experience high levels of maternal stress as well as poor sleep
      and well-being. Given the fact that the number of children with DDs has
      increased, an up-to-date literature review is necessary to identify factors
      associated with maternal stress, sleep, and well-being. In addition,
      understanding these factors and their relationships may provide better strategies
      in designing effective interventions that can reduce the burden in mothers of
      children with DDs. This review summarized 28 scientific research papers that
      examined maternal stress, sleep, and well-being in mothers of children with DDs
      in past 12 years. The study findings indicate that mothers of children with DDs
      experience higher levels of stress than mothers of typically developing children,
      and it remains high over time. In addition, these mothers often encounter
      depressive symptoms as well as poor sleep quality. The study results also reveal
      that there is a bidirectional relationship between maternal stress and depressive
      symptoms as well as between poor sleep quality and depressive symptoms. For
      example, higher stress mothers experienced more depressive symptoms. Mothers of
      children with DDs with poor sleep quality are significantly associated with more
      depressive symptoms. Child behavior problems were significantly associated with
      both maternal stress and depressive symptoms, but cautious interpretation is
      warranted due to the shared variance between child behavior problems, maternal
      stress, and depressive symptoms. Methodological guidelines for future research
      involve the use of reliable and valid instruments for the measurement of child
      behavior problems, maternal stress, and sleep. Recommendations for future
      research are included. 

PMID- 24080070
TI  - Newly emerging C group enteroviruses may elude diagnosis due to a divergent 5'
      UTR.
AB  - Human enterovirus (HEV) 105 was first reported in 2012 in children from Peru and
      Congo. We report on the identification of a novel HEV-C105 strain in a pediatric
      patient in Cyprus with an upper respiratory tract infection. Sequence alignment
      and phylogenetic analysis of 5'-UTRs of all known HEVs revealed that our isolate
      belongs to a group of recently identified HEV-C viruses exhibiting a 5'-UTR
      distinct from all other previously known enteroviruses. This has important
      implications for diagnosis, as this region is the primary target for diagnostic
      assays. Increased awareness in laboratories may thus increase the rate of
      detection of enteroviruses belonging to this subspecies, or lead to the discovery
      of further genotypes. 

PMID- 24080071
TI  - Detailed glycan structural characterization by electronic excitation
      dissociation.
AB  - The structural complexity and diversity of glycans parallel their multilateral
      functions in living systems. To better understand the vital roles glycans play in
      biological processes, it is imperative to develop analytical tools that can
      provide detailed glycan structural information. This was conventionally achieved
      by multistage tandem mass spectrometry (MS(n)) analysis using collision-induced
      dissociation (CID) as the fragmentation method. However, the MS(n) approach lacks
      the sensitivity and throughput needed to analyze complex glycan mixtures from
      biological sources, often available in limited quantities. We define herein the
      critical parameters for a recently developed fragmentation technique, electronic
      excitation dissociation (EED), which can yield rich structurally informative
      fragment ions during liquid chromatographic (LC)-MS/MS analysis of glycans. We
      further demonstrate that permethylation, reducing end labeling and judicious
      selection of the metal charge carrier, can greatly facilitate spectral
      interpretation. With its high sensitivity, throughput, and compatibility with
      online chromatographic separation techniques, EED appears to hold great promise
      for large-scale glycomics studies. 

PMID- 24080072
TI  - Biomarkers of necrotising enterocolitis.
AB  - Different categories of biomarkers of necrotising enterocolitis (NEC), including
      (i) non-specific mediators of the inflammatory cascade, e.g. acute phase
      reactants, chemokines, cytokines, and cell surface antigens, (ii) enhanced non
      specific biomarkers, and (iii) specific gut-associated proteins, have distinctive
      biochemical characteristics and properties. The appropriateness of using these
      mediators in specific clinical situations, and the pros and cons of their
      applications as indicators or predictors of intestinal injury and NEC are
      highlighted. Many potentially new biomarkers such as micro-RNA, volatile organic
      compounds and gut microbiomes are currently under investigation. A stringent
      protocol for biomarker discovery is revealed so that investigators can consider
      this methodology as a reference for future discovery of organ-specific and/or
      disease-specific biomarkers for preterm infants. 

PMID- 24080074
TI  - Relationships between spoken word and sign processing in children with cochlear
      implants.
AB  - The effect of using signed communication on the spoken language development of
      deaf children with a cochlear implant (CI) is much debated. We report on two
      studies that investigated relationships between spoken word and sign processing
      in children with a CI who are exposed to signs in addition to spoken language.
      Study 1 assessed rapid word and sign learning in 13 children with a CI and found
      that performance in both language modalities correlated positively. Study 2
      tested the effects of using sign-supported speech on spoken word processing in
      eight children with a CI, showing that simultaneously perceiving signs and spoken
      words does not negatively impact their spoken word recognition or learning.
      Together, these two studies suggest that sign exposure does not necessarily have
      a negative effect on speech processing in some children with a CI. 

PMID- 24080073
TI  - The relationship between Clinical Trial Network protocol involvement and quality
      of substance use disorder treatment.
AB  - The National Institute on Drug Abuse's Clinical Trials Network (CTN) is a
      practice-based research network that partners academic researchers with community
      based substance use disorder (SUD) treatment programs designed primarily to
      conduct effectiveness trials of promising interventions. A secondary goal of the
      CTN is to widely disseminate results of these trials and thus improve the quality
      of SUD treatment in the US. Drawing on data from 156 CTN programs, this study
      examines the association between involvement in CTN protocols and overall
      treatment quality measured by a comprehensive index of 35 treatment services.
      Negative binomial regression models show that treatment programs participating in
      a greater number of CTN protocols had significantly higher levels of treatment
      quality, an association that held after controlling for key organizational
      characteristics. These findings contribute to the growing body of research on the
      role of practice-based research networks in promoting health care quality. 

PMID- 24080075
TI  - Noise levels in primary schools of medium sized city in Greece.
AB  - This study presents and evaluates noise levels recorded at 15 school complexes in
      order to describe the indoor as well as the outdoor acoustic environment of
      schools and gain insight on controlling factors. Noise levels at the roadside in
      front of the school, the schoolyard, and 41 classrooms, both occupied and
      unoccupied, were simultaneously and continuously recorded through the course of a
      daily timetable (08:20-13:10). The average speech noise level of teachers was
      separately measured for 1min periods. Indoor noise levels, in all cases, were
      much higher than internationally recommended values: LAeq,5min averaged 69.0dB in
      occupied classrooms, and 47.1dB in unoccupied ones. Average speech-to-noise ratio
      (SNR) was estimated to be 12.0dB(A) during teaching, whereas both indoor and
      outdoor noise levels were significantly elevated during break time and outdoor
      physical-educational activities. Corresponding measurements of indoor and outdoor
      noise suggest that noise from the outside (road and schoolyard) affects the
      background noise level in the classrooms, however in varying degrees, depending
      on the specific layout and road traffic characteristics. Using double glazing
      diminishes this effect. 

PMID- 24080076
TI  - CHITIN--a promising biomaterial for tissue engineering and stem cell
      technologies.
AB  - Chitin, after cellulose, is the second most abundant natural polymer. With a 200
      year history of scientific research, chitin is beginning to see fruitful
      application in the fields of stem cell and tissue engineering. To date, however,
      research in chitin as a biomaterial appears to lag far behind that of its close
      relative, chitosan, due to the perceived difficulty in processing chitin. This
      review presents methods to improve the processability of chitin, and goes on
      further to discuss the unique physicochemical and biological characteristics of
      chitin that favor it as a biomaterial for regenerative medicine applications.
      Examples of the latter are presented, with special attention on the qualities of
      chitin that make it inherently suitable as scaffolds and matrices for tissue
      engineering, stem cell propagation and differentiation. 

PMID- 24080077
TI  - Brain Painting: usability testing according to the user-centered design in end
      users with severe motor paralysis.
AB  - BACKGROUND: For many years the reestablishment of communication for people with
      severe motor paralysis has been in the focus of brain-computer interface (BCI)
      research. Recently applications for entertainment have also been developed. Brain
      Painting allows the user creative expression through painting pictures.
      OBJECTIVE: The second, revised prototype of the BCI Brain Painting application
      was evaluated in its target function - free painting - and compared to the P300
      spelling application by four end users with severe disabilities. METHODS:
      According to the International Organization for Standardization (ISO), usability
      was evaluated in terms of effectiveness (accuracy), efficiency (information
      transfer rate (ITR)), utility metric, subjective workload (National Aeronautics
      and Space Administration Task Load Index (NASA TLX)) and user satisfaction
      (Quebec User Evaluation of Satisfaction with assistive Technology (QUEST) 2.0 and
      Assistive Technology Device Predisposition Assessment (ATD PA), Device Form).
      RESULTS: The results revealed high performance levels (M>=80% accuracy) in the
      free painting and the copy painting conditions, ITRs (4.47-6.65bits/min)
      comparable to other P300 applications and only low to moderate workload levels (5
      49 of 100), thereby proving that the complex task of free painting did neither
      impair performance nor impose insurmountable workload. Users were satisfied with
      the BCI Brain Painting application. Main obstacles for use in daily life were the
      system operability and the EEG cap, particularly the need of extensive support
      for adjustment. CONCLUSION: The P300 Brain Painting application can be operated
      with high effectiveness and efficiency. End users with severe motor paralysis
      would like to use the application in daily life. User-friendliness, specifically
      ease of use, is a mandatory necessity when bringing BCI to end users. Early and
      active involvement of users and iterative user-centered evaluation enable
      developers to work toward this goal.

PMID- 24080078
TI  - Asynchronous gaze-independent event-related potential-based brain-computer
      interface.
AB  - OBJECTIVE: In this study a gaze independent event related potential (ERP)-based
      brain computer interface (BCI) for communication purpose was combined with an
      asynchronous classifier endowed with dynamical stopping feature. The aim was to
      evaluate if and how the performance of such asynchronous system could be
      negatively affected in terms of communication efficiency and robustness to false
      positives during the intentional no-control state. MATERIAL AND METHODS: The
      proposed system was validated with the participation of 9 healthy subjects. A
      comparison was performed between asynchronous and synchronous classification
      technique outputs while users were controlling the same gaze independent BCI
      interface. The performance of both classification techniques were assessed both
      off-line and on-line by means of the efficiency metric introduced by Bianchi et
      al. (2007). This latter metric allows to set a different misclassification cost
      for wrong classifications and abstentions. Robustness was evaluated as the rate
      of false positives occurring during voluntary no-control states. RESULTS: The
      asynchronous classifier did not exhibited significantly higher accuracy or lower
      error rate with respect to the synchronous classifier (accuracy: 74.66% versus
      87.96%, error rate: 7.11% versus 12.04% respectively). However, the on-line and
      off-line analysis revealed that the communication efficiency was significantly
      improved (p<.05) with the asynchronous classification modality as compared with
      the synchronous. Furthermore, the asynchronous classifier proved to be robust to
      false positives during intentional no-control state which occur during the
      ongoing visual stimulation (less than 1 false positive every 6min). CONCLUSION:
      As such, the proposed ERP-BCI system which combines an asynchronous classifier
      with a gaze independent interface is a promising solution to be further explored
      in order to increase the general usability of ERP-based BCI systems designed for
      severely disabled people with an impairment of the voluntary control of eye
      movements. In fact, the asynchronous classifier can improve communication
      efficiency automatically adapting the number of stimulus repetitions to the
      current user's state and suspending the control if he/she does not intend to
      select an item.

PMID- 24080079
TI  - Comparative analysis of a-priori and a-posteriori dietary patterns using state-of
      the-art classification algorithms: a case/case-control study.
AB  - OBJECTIVE: To compare the accuracy of a-priori and a-posteriori dietary patterns
      in the prediction of acute coronary syndrome (ACS) and ischemic stroke. This is
      actually the first study to employ state-of-the-art classification methods for
      this purpose. METHODS AND MATERIALS: During 2009-2010, 1000 participants were
      enrolled; 250 consecutive patients with a first ACS and 250 controls (60+/-12
      years, 83% males), as well as 250 consecutive patients with a first stroke and
      250 controls (75+/-9 years, 56% males). The controls were population-based and
      age-sex matched to the patients. The a-priori dietary patterns were derived from
      the validated MedDietScore, whereas the a-posteriori ones were extracted from
      principal components analysis. Both approaches were modeled using six
      classification algorithms: multiple logistic regression (MLR), naive Bayes,
      decision trees, repeated incremental pruning to produce error reduction (RIPPER),
      artificial neural networks and support vector machines. The classification
      accuracy of the resulting models was evaluated using the C-statistic. RESULTS:
      For the ACS prediction, the C-statistic varied from 0.587 (RIPPER) to 0.807 (MLR)
      for the a-priori analysis, while for the a-posteriori one, it fluctuated between
      0.583 (RIPPER) and 0.827 (MLR). For the stroke prediction, the C-statistic varied
      from 0.637 (RIPPER) to 0.767 (MLR) for the a-priori analysis, and from 0.617
      (decision tree) to 0.780 (MLR) for the a-posteriori. CONCLUSION: Both dietary
      pattern approaches achieved equivalent classification accuracy over most
      classification algorithms. The choice, therefore, depends on the application at
      hand.

PMID- 24080080
TI  - Brain-computer interface controlled gaming: evaluation of usability by severely
      motor restricted end-users.
AB  - OBJECTIVE: Connect-Four, a new sensorimotor rhythm (SMR) based brain-computer
      interface (BCI) gaming application, was evaluated by four severely motor
      restricted end-users; two were in the locked-in state and had unreliable eye
      movement. METHODS: Following the user-centred approach, usability of the BCI
      prototype was evaluated in terms of effectiveness (accuracy), efficiency
      (information transfer rate (ITR) and subjective workload) and users'
      satisfaction. RESULTS: Online performance varied strongly across users and
      sessions (median accuracy (%) of end-users: A=.65; B=.60; C=.47; D=.77). Our
      results thus yielded low to medium effectiveness in three end-users and high
      effectiveness in one end-user. Consequently, ITR was low (0.05-1.44bits/min).
      Only two end-users were able to play the game in free-mode. Total workload was
      moderate but varied strongly across sessions. Main sources of workload were
      mental and temporal demand. Furthermore, frustration contributed to the
      subjective workload of two end-users. Nevertheless, most end-users accepted the
      BCI application well and rated satisfaction medium to high. Sources for
      dissatisfaction were (1) electrode gel and cap, (2) low effectiveness, (3) time
      consuming adjustment and (4) not easy-to-use BCI equipment. All four end-users
      indicated ease of use as being one of the most important aspect of BCI.
      CONCLUSION: Effectiveness and efficiency are lower as compared to applications
      using the event-related potential as input channel. Nevertheless, the SMR-BCI
      application was satisfactorily accepted by the end-users and two of four could
      imagine using the BCI application in their daily life. Thus, despite moderate
      effectiveness and efficiency BCIs might be an option when controlling an
      application for entertainment.

PMID- 24080081
TI  - Extended-spectrum beta-lactamase-producing Enterobacteriaceae carriage upon
      hospital admission: prevalence and risk factors.
AB  - The aim of this study was to assess the value of surveillance cultures in
      identifying extended-spectrum beta-lactamase-producing Enterobacteriaceae (ESBL)
      carriers upon admission to hospital, and to identify risk factors for carriage.
      This prospective cross-sectional study included all hospital admissions over one
      week. Of 525 patients screened, 56 were positive for ESBLs. Half were only
      identified through screening. Four independent risk factors were identified:
      nursing home residency, hospitalization in the previous year, prior antibiotic
      treatment and prior ESBL carriage. Over 50% of the screened patients had at least
      one risk factor. By screening this targeted population, 87.5% of positive
      patients would have been identified. 

PMID- 24080082
TI  - Response to M.H. Stevens and N.M. Klinger, re: Bacterial recolonization of the
      skin and wound contamination during cardiac surgery.

PMID- 24080083
TI  - Impact of an educational intervention upon the hand hygiene compliance of
      children.
AB  - BACKGROUND: Hand hygiene compliance is the single most effective way to reduce
      healthcare-associated infections. Children are notoriously vulnerable to
      infection as well as acting as conduits to transmission. Based on these
      observations, the authors formulated the hypothesis that behavioural change which
      improved children's hand hygiene compliance would decrease the spread of
      infectious diseases. AIM: To create an educational intervention to induce long
      term behavioural change culminating in increased hand hygiene compliance of
      children, and thus a decrease in the rate of infections. METHODS: Focus groups
      conducted during interactive teaching sessions identified what children felt
      would help them to increase their hand hygiene compliance. This informed the
      design of an educational device that was subsequently trialled to measure its
      effectiveness in increasing hand hygiene compliance. Initial developmental stages
      were conducted in two schools in the East Midlands with study participants aged 5
      8 years; the device was subsequently used in a healthcare setting to assess
      deployment flexibility. FINDINGS: Focus groups indicated that children enjoyed
      interactive learning, developed knowledge about cross-transmission of infections,
      and became motivated to encourage others to improve hand hygiene compliance.
      Microbiological swabbing verified the presence of pathogens on children's hands
      and environmental surfaces that could serve as reservoirs of infection, and
      questionnaires indicated an increase in handwashing following the intervention.
      CONCLUSION: Educational interventions have the potential to increase hand hygiene
      and reduce the transmission of infections.

PMID- 24080084
TI  - A role for CMTM7 in BCR expression and survival in B-1a but not B-2 cells.
AB  - B-1 cells are an important cell population for the production of natural
      antibodies and front-line host defense. Here, we show that the MARVEL-domain
      containing membrane protein CMTM7 (CKLF-like MARVEL transmembrane domain
      containing 7) plays a critical role in BCR expression and survival in B-1a cells.
      We analyzed lymphocyte development in Rag1-/- mice reconstituted with
      Cmtm7(flox/+) fetal liver cells because of the unexpected lethality of the
      Cmtm7(flox/+) heterozygotes. We found a mild reduction of serum IgM and a
      significantly reduced B-1a population in the peritoneal cavity of Rag1-/- mice
      reconstituted with Cmtm7(flox/+) cells compared with those reconstituted with
      wild-type (WT) cells. The reduction of B-1a cells in Cmtm7(flox/+) mice was
      associated with reduced BCR expression and increased spontaneous cell death in
      these cells. In addition, both B-1a and B-1b cells derived from Cmtm7(flox/+)
      fetal liver cells contained a lower frequency of cells capable of spontaneously
      differentiating into IgM-secreting plasma cells than did those derived from WT
      fetal liver cells. Furthermore, Cmtm7(flox/+) B-1a and B-1b cells responded
      poorly to LPS-induced proliferation. In striking contrast to the defects in B-1
      cells, Cmtm7(flox/+) B-2 cells did not show obvious abnormalities when compared
      with WT B-2 cells. These results demonstrate a specific role for CMTM7 in BCR
      expression and survival in B-1a cells.

PMID- 24080086
TI  - Influence of adrenocorticotrophin hormone challenge and external factors (age,
      sex, and body region) on hair cortisol concentration in Canada lynx (Lynx
      canadensis).
AB  - Land use changes are a significant factor influencing the decline of felid
      populations. However, additional research is needed to better understand how
      these factors influence populations in the wild. Hormone analysis can provide
      valuable information on the basic physiology and overall health of an animal, and
      enzyme immunoassays (EIA) are generally used for hair hormone analysis but must
      first be validated for the substrate of choice and species of interest. To date,
      hormone assays from hair have not been validated for Felidae, despite that the
      method holds considerable promise for non-invasive sampling of free-ranging
      animals. We sought to: (1) evaluate whether increased adrenocorticotrophin
      hormone (ACTH) during the period of hair growth results in elevated hair
      cortisol; (2) validate the enzyme immunoassay used; and (3) identify any
      variations in hair cortisol between age, sex and body regions, using Canada lynx.
      We quantified hair cortisol concentrations in captive animals through an ACTH
      challenge and collected samples from legally harvested lynx to compare
      variability between body regions. An EIA was validated for the analysis of hair
      cortisol. Lynx (n=3) had a qualitative increase in hair cortisol concentration
      following an ACTH challenge in captive animals (20 IU/kg of body weight weekly
      for 5 weeks), thereby supporting the use of an EIA to quantify cortisol values in
      hair. Based on our analysis of sampled lynx pelts, we found that hair cortisol
      did not vary between age and sex, but varied within the foot/leg region to a
      greater extent than between individuals. We recommend that future studies
      identify a standardized location for hair cortisol sampling.

PMID- 24080085
TI  - Humoral control of cardiac remodeling in fish: role of Angiotensin II.
AB  - Angiotensin II (AngII), the principal effector of the Renin-Angiotensin-System
      (RAS), is a multipotent hormone whose biological actions include short-term
      modulation as well as long-term adjustments. In the eel heart, AngII elicits
      short-term inotropic and chronotropic effects. However, information regarding the
      influence of AngII on cardiac remodeling, expressed as morphological and
      hemodynamic changes, is lacking. To clarify the putative actions of AngII on eel
      cardiac remodeling, we used freshwater eels (Anguilla anguilla) intraperitoneally
      injected for 4 weeks with saline or AngII (0.4 or 1.2 nmol g BW(-1)) or AngII
      (1.2 nmol g BW(-1)) plus the AT2 receptor antagonist CGP42112. Using an in vitro
      working heart preparation, the cardiac response (stroke volume changes) to
      preload and afterload increases has been evaluated. Hearts of all groups showed
      similar Frank-Starling responses. However, in response to afterload increases,
      stroke volume rapidly decreased in control hearts, while it was better maintained
      in AngII-treated counterparts. These effects were abolished by an antagonist of
      the AT2 receptor, whose cardiac expression was revealed by western blotting
      analysis. We also found by immunolocalization and immunoblotting that AngII
      influences both expression and localization of molecules which regulate cell
      growth [such as c-kit, heat shock protein 90 (Hsp-90), endothelial Nitric Oxide
      Synthase "(eNOS)-like" isoform] and apoptosis [i.e. apoptosis repressor with CARD
      domain (ARC)], thus playing a role in cardiac long-term adjustments. These
      results point to a role of AngII in eel heart remodeling, providing new insights
      regarding the modulation of cardiac plasticity in fish.

PMID- 24080087
TI  - Aldehyde dehydrogenase-1a1 induces oncogene suppressor genes in B cell
      populations.
AB  - The deregulation of B cell differentiation has been shown to contribute to
      autoimmune disorders, hematological cancers, and aging. We provide evidence that
      the retinoic acid-producing enzyme aldehyde dehydrogenase 1a1 (Aldh1a1) is an
      oncogene suppressor in specific splenic IgG1(+)/CD19(-) and IgG1(+)/CD19(+) B
      cell populations. Aldh1a1 regulated transcription factors during B cell
      differentiation in a sequential manner: 1) retinoic acid receptor alpha (Rara) in
      IgG1(+)/CD19(-) and 2) zinc finger protein Zfp423 and peroxisome proliferator
      activated receptor gamma (Pparg) in IgG1(+)/CD19(+) splenocytes. In Aldh1a1(-/-)
      mice, splenic IgG1(+)/CD19(-) and IgG1(+)/CD19(+) B cells acquired expression of
      proto-oncogenic genes c-Fos, c-Jun, and Hoxa10 that resulted in splenomegaly.
      Human multiple myeloma B cell lines also lack Aldh1a1 expression; however,
      ectopic Aldh1a1 expression rescued Rara and Znf423 expressions in these cells.
      Our data highlight a mechanism by which an enzyme involved in vitamin A
      metabolism can improve B cell resistance to oncogenesis. 

PMID- 24080088
TI  - BAG3 sensitizes cancer cells exposed to DNA damaging agents via direct
      interaction with GRP78.
AB  - Bcl-2 associated athanogene 3 (BAG3) has a modular structure that contains a BAG
      domain, a WW domain, a proline-rich (PxxP) domain to mediate potential
      interactions with chaperons and other proteins that participate in more than one
      signal transduction. In search for novel interacting partners, the current study
      identified that 78kDa glucose-regulated protein (GRP78) was a novel partner
      interacting with BAG3. Interaction between GRP78 and BAG3 was confirmed by
      coimmunoprecipitation and glutathione S-transferase (GST) pulldown. We also
      identified that the ATPase domain of GRP78 and BAG domain of BAG3 mediated their
      interaction. Counterintuitive for a prosurvival protein, BAG3 was found to
      promote the cytotoxicity of breast cancer MCF7, thyroid cancer FRO and glioma U87
      cells subjected to genotoxic stress. In addition, the current study demonstrated
      that BAG3 interfered with the formation of the antiapoptotic GRP78-procaspase-7
      complex, which resulted in an increased genotoxic stress-induced cytotoxicity in
      cancer cells. Furthermore, overexpression of GRP78 significantly blocked the
      enhancing effects of BAG3 on activation of caspase-7 and induction of apoptosis
      by genotoxic stress. Overall, these results suggested that through direct
      interaction BAG3 could prevent the antiapoptotic effect of GRP78 upon genotoxic
      stress. 

PMID- 24080089
TI  - Curli biogenesis: order out of disorder.
AB  - Many bacteria assemble extracellular amyloid fibers on their cell surface.
      Secretion of proteins across membranes and the assembly of complex macromolecular
      structures must be highly coordinated to avoid the accumulation of potentially
      toxic intracellular protein aggregates. Extracellular amyloid fiber assembly
      poses an even greater threat to cellular health due to the highly aggregative
      nature of amyloids and the inherent toxicity of amyloid assembly intermediates.
      Therefore, temporal and spatial control of amyloid protein secretion is
      paramount. The biogenesis and assembly of the extracellular bacterial amyloid
      curli is an ideal system for studying how bacteria cope with the many challenges
      of controlled and ordered amyloid assembly. Here, we review the recent progress
      in the curli field that has made curli biogenesis one of the best-understood
      functional amyloid assembly pathways. This article is part of a Special Issue
      entitled: Protein trafficking and secretion in bacteria. Guest Editors:
      Anastassios Economou and Ross Dalbey. 

PMID- 24080091
TI  - Mesoporous TiO2 single crystals: facile shape-, size-, and phase-controlled
      growth and efficient photocatalytic performance.
AB  - In this work, we have succeeded in preparing rutile and anatase TiO2 mesoporous
      single crystals with diverse morphologies in a controllable fashion by a simple
      silica-templated hydrothermal method. A simple in-template crystal growth process
      was put forward, which involved heterogeneous crystal nucleation and oriented
      growth within the template, a sheer spectator, and an excluded volume, i.e.,
      crystal growth by faithful negative replication of the silica template. A series
      of mesoporous single-crystal structures, including rutile mesoporous TiO2
      nanorods with tunable sizes and anatase mesoporous TiO2 nanosheets with dominant
      {001} facets, have been synthesized to demonstrate the versatility of the
      strategy. The morphology, size, and phase of the TiO2 mesoporous single crystals
      can be tuned easily by varying the external conditions such as the hydrohalic
      acid condition, seed density, and temperature rather than by the silica template,
      which merely serves for faithful negative replication but without interfering in
      the crystallization process. To demonstrate the application value of such TiO2
      mesoporous single crystals, photocatalytic activity was tested. The resultant
      TiO2 mesoporous single crystals exhibited remarkable photocatalytic performance
      on hydrogen evolution and degradation of methyl orange due to their increased
      surface area, single-crystal nature, and the exposure of reactive crystal facets
      coupled with the three-dimensionally connected mesoporous architecture. It was
      found that {110} facets of rutile mesoporous single crystals can be considered
      essentially as reductive sites with a key role in the photoreduction, while {001}
      facets of anatase mesoporous single crystals provided oxidation sites in the
      oxidative process. Such shape- and size-controlled rutile and anatase mesoporous
      TiO2 single crystals hold great promise for building energy conversion devices,
      and the simple solution-based hydrothermal method is extendable to the synthesis
      of other mesoporous single crystals beyond TiO2. 

PMID- 24080090
TI  - The IC138 and IC140 intermediate chains of the I1 axonemal dynein complex bind
      directly to tubulin.
AB  - Dyneins are minus end directed microtubule motors that play a critical role in
      ciliary and flagellar movement. Ciliary dyneins, also known as axonemal dyneins,
      are characterized based on their location on the axoneme, either as outer dynein
      arms or inner dynein arms. The I1 dynein is the best-characterized subspecies of
      the inner dynein arms; however the interactions between many of the components of
      the I1 complex and the axoneme are not well defined. In an effort to elucidate
      the interactions in which the I1 components are involved, we performed zero
      length crosslinking on axonemes and studied the crosslinked products formed by
      the I1 intermediate chains, IC138 and IC140. Our data indicate that IC138 and
      IC140 bind directly to microtubules. Mass-spectrometry analysis of the
      crosslinked product identified both alpha- and beta-tubulin as the IC138 and
      IC140 binding partners. This was further confirmed by crosslinking experiments
      carried out on purified I1 fractions bound to Taxol-stabilized microtubules.
      Furthermore, the interaction between IC140 and tubulin is lost when IC138 is
      absent. Our studies support previous findings that intermediate chains play
      critical roles in the assembly, axonemal targeting and regulation of the I1
      dynein complex. 

PMID- 24080092
TI  - Comparative performance of diabetes-specific and general population-based
      cardiovascular risk assessment models in people with diabetes mellitus.
AB  - AIM: Multivariable models for estimating cardiovascular disease (CVD) risk in
      people with diabetes comprise general population-based models and those from
      diabetic cohorts. Whether one set of models should receive preference is unclear.
      We evaluated the evidence on direct comparisons of the performance of general
      population vs diabetes-specific CVD risk models in people with diabetes. METHODS:
      MEDLINE and EMBASE databases were searched up to March 2013. Two reviewers
      independently identified studies that compared the performance of general CVD
      models vs diabetes-specific ones in the same group of people with diabetes.
      Independent, dual data extraction on study design, risk models, outcomes; and
      measures of performance was conducted. RESULTS: Eleven articles reporting on 22
      pair wise comparisons of a diabetes-specific model (UKPDS, ADVANCE and DCS risk
      models) to a general population model (three variants of the Framingham model,
      Prospective Cardiovascular Munster [PROCAM] score, CardioRisk Manager [CRM],
      Joint British Societies Coronary Risk Chart [JBSRC], Progetto Cuore algorithm and
      the CHD-Riskard algorithm) were eligible. Absolute differences in C-statistic of
      diabetes-specific vs general population-based models varied from -0.13 to 0.09.
      Comparisons for other performance measures were unusual. Outcomes definitions
      were congruent with those applied during model development. In 14 comparisons,
      the UKPDS, ADVANCE or DCS diabetes-specific models were superior to the general
      population CVD risk models. Authors reported better C-statistic for models they
      developed. CONCLUSION: The limited existing evidence suggests a possible
      discriminatory advantage of diabetes-specific over general population-based
      models for CVD risk stratification in diabetes. More robust head-to-head
      comparisons are needed to confirm this trend and strengthen recommendations.

PMID- 24080093
TI  - The temporal relationship between drug supply indicators: an audit of
      international government surveillance systems.
AB  - OBJECTIVES: Illegal drug use continues to be a major threat to community health
      and safety. We used international drug surveillance databases to assess the
      relationship between multiple long-term estimates of illegal drug price and
      purity. DESIGN: We systematically searched for longitudinal measures of illegal
      drug supply indicators to assess the long-term impact of enforcement-based supply
      reduction interventions. SETTING: Data from identified illegal drug surveillance
      systems were analysed using an a priori defined protocol in which we sought to
      present annual estimates beginning in 1990. Data were then subjected to trend
      analyses. MAIN OUTCOME MEASURES: Data were obtained from government surveillance
      systems assessing price, purity and/or seizure quantities of illegal drugs;
      systems with at least 10 years of longitudinal data assessing price,
      purity/potency or seizures were included. RESULTS: We identified seven
      regional/international metasurveillance systems with longitudinal measures of
      price or purity/potency that met eligibility criteria. In the USA, the average
      inflation-adjusted and purity-adjusted prices of heroin, cocaine and cannabis
      decreased by 81%, 80% and 86%, respectively, between 1990 and 2007, whereas
      average purity increased by 60%, 11% and 161%, respectively. Similar trends were
      observed in Europe, where during the same period the average inflation-adjusted
      price of opiates and cocaine decreased by 74% and 51%, respectively. In
      Australia, the average inflation-adjusted price of cocaine decreased 14%, while
      the inflation-adjusted price of heroin and cannabis both decreased 49% between
      2000 and 2010. During this time, seizures of these drugs in major production
      regions and major domestic markets generally increased. CONCLUSIONS: With few
      exceptions and despite increasing investments in enforcement-based supply
      reduction efforts aimed at disrupting global drug supply, illegal drug prices
      have generally decreased while drug purity has generally increased since 1990.
      These findings suggest that expanding efforts at controlling the global illegal
      drug market through law enforcement are failing.

PMID- 24080094
TI  - Common psychosocial stressors in middle-aged women related to longstanding
      distress and increased risk of Alzheimer's disease: a 38-year longitudinal
      population study.
AB  - OBJECTIVE: To study the relation among psychosocial stressors, long-standing
      distress and incidence of dementia, in a sample of women followed from midlife to
      late life. DESIGN: Prospective longitudinal population study. SETTING: The
      analyses originate from the prospective population study of women in Gothenburg,
      Sweden, a representative sample of women examined in 1968 (participation rate
      90%) and re-examined in 1974, 1980, 1992, 2000 and 2005. PARTICIPANTS: 800 women
      born in 1914, 1918, 1922 and 1930 who were systematically selected for a
      psychiatric examination at baseline, in 1968. PRIMARY AND SECONDARY OUTCOME
      MEASURES: 18 psychosocial stressors (eg, divorce, widowhood, work problems and
      illness in relative) were obtained at baseline. Symptoms of distress were
      measured according to a standardised question at each study wave. Dementia was
      diagnosed according to Diagnostic and Statistical Manual of Mental Disorders (DSM
      III-R) criteria based on information from neuropsychiatric examinations,
      informant interviews, hospital records, and registry data, and measured through
      the whole study period. RESULTS: During the 37 years of follow-up, 153 women
      developed dementia (104 of those had Alzheimer's disease (AD)). Number of
      psychosocial stressors in 1968 was associated (HR, 95% CI) with higher incidence
      of dementia (1.15, 1.04 to 1.27) and AD (1.20, 1.07 to 1.35) between 1968 and
      2005, in multivariate Cox regressions. Number of psychosocial stressors in 1968
      was also associated (OR, 95% CI) with distress in 1968 (1.48, 1.32 to 1.67), 1974
      (1.31, 1.17 to 1.46), 1980 (1.27, 1.11 to 1.45), 2000 (1.39, 1.14 to 1.70) and
      2005 (1.35, 1.02 to 1.79), in multivariate logistic regressions. Number of
      psychosocial stressors (HR 1.17, 95% CI 1.03 to 1.33) and long-standing distress
      (1968-1974-1980) (HR 1.58, 95% CI 1.03 to 2.45) were independently associated
      with AD. CONCLUSIONS: Our study shows that common psychosocial stressors may have
      severe and long-standing physiological and psychological consequences. However,
      more studies are needed to confirm these results and investigate whether more
      interventions such as stress management and behavioural therapy should be
      initiated in individuals who have experienced psychosocial stressors.

PMID- 24080095
TI  - Effectiveness of Emergency Medicine Wards in reducing length of stay and
      overcrowding in emergency departments.
AB  - OBJECTIVE: This study aims to evaluate the effectiveness of an Emergency Medicine
      Ward (EMW) in reducing the length of stay (LOS) in the emergency department,
      length of hospitalization, emergency medical admission rate, and the hospital bed
      occupancy rate. METHODS: This study is a cross-sectional, observational study
      with a retrospective, quantitative record review conducted at the EMW of a
      regional acute hospital in Hong Kong from January 2009 to June 2009. RESULTS:
      During the study, a retrospective audit was conducted on 1834 patient records.
      The five main groups of patients admitted into EMW suffered from cardiac disease
      (26.5%), pneumonia (19.6%), dizziness (16.2%), Chronic Obstructive Pulmonary
      Disease (12.3%), and gastroenteritis (7.9%). The mean LOS in the EMW was 1.27
      days (SD=0.59). The average emergency medical admission rate within the six-month
      period was significantly reduced relative to that before the EMW became
      operational (January 2008 to June 2008). Clinically, the medical in-patient bed
      occupancy was significantly reduced by 6.2%. The average LOS during in-patient
      hospitalization after the EMW was established decreased to 4.13 days from the
      previous length of 5.16 days. CONCLUSIONS: EMWs effectively reduce both the LOS
      during in-patient hospitalization and the avoidable medical admission rate.

PMID- 24080096
TI  - A bioassessment of soil nickel genotoxic effect in orchard planted on
      rehabilitated coalmine overburden.
AB  - Environmental problems of non-rehabilitated overburden material are present in
      surrounding of open coal mines worldwide. Ecological restoration of this soil
      material usually deals with the improvement of its bad physico-chemical
      properties and its poor nutrient status, sometimes associated with heavy metal
      problems. Applied overburden restoration by planting orchard (1990) is assumed to
      be the first of its kind at opencast mines globally, so that present work was
      aimed at acquiring information about its efficiency of the applied measures
      concerning their possible use in agriculture. Various physical and chemical
      properties, together with the pseudo total and DTPA extractable metals (Fe, Mn,
      Cu, Zn, Co, Ni, Pb, Cr, Cd) as well as sequential Ni extraction analyses, was
      measured, in order to evaluate the impact of soil's Ni level (76.3-111.7 mg kg-1)
      on decreasing yields of apples, pears and plums. As a general pattern, reclaimed
      soil was significantly enriched with organic matter (>2.5 percent) and nutrients
      compared to the initial (2 m depth) and non-reclaimed adjacent soil, approving
      this method for overburden restoration. Despite low Ni concentration in organs,
      Ni accumulation in a fruits' trees qualified these species as suitable for
      phytostabilization of present heavy metals, with a woody biomass as a large and
      important sink for Ni, especially in the roots. Applied cytogenetic studies
      evaluate the lack of genotoxic effect of nickel (Ni) on the gametic cells of
      investigated species, having no significant effect on meiosis and pollen
      germination. Most of the found anomalies were in apples, as a kind of aberrations
      with sticky figures and chromosome lagging, should be ascribed to the
      environmental and genetic interaction over the aging of trees.

PMID- 24080097
TI  - Effect of exposure to contaminated pond sediments on survival, development, and
      enzyme and blood biomarkers in veined treefrog (Trachycephalus typhonius)
      tadpoles.
AB  - Sediments are important elements of aquatic ecosystems and in general sediments
      accumulate diverse toxic substances. Amphibians potentially have a greater risk
      of exposure to contaminants in sediments, and the test of sediments provides
      first lines of evidences. Sediment outdoor microcosm experiments were conducted
      to analyze biological endpoints (survival, development, growth, and morphological
      and organ malformation), enzyme activity (butyrylcholinesterase, BChE;
      glutathione-S-transferase, GST; and catalase, CAT) and blood biomarkers in veined
      treefrog Trachycephalus typhonius tadpoles, a widespread neotropical species.
      Hatching (stage 23) of T. thyphonius was exposed until they reached metamorphosis
      (stage 46). Sediment tests were performed and four different treatments were
      used: three ponds (LTPA, ISP, and SSP) influenced by industrial and agricultural
      activities and a reference treatment from a forest (RFS). Physical and chemical
      variables and concentration of nutrients, pesticide residues, and metals were
      determined. One treatment was metal-rich (LPTA) and two were nutrient-rich (ISP
      and SSP). Sediment treatments had no significant effect on survival; in contrast
      they had significant sublethal effects on T. typhonius larval development and
      growth rates, and affected overall size and shape at stage 38. Principally, in
      LPTA animals were significantly larger than in RFS, exhibiting swollen bodies,
      tail muscles and tail fin. In addition, metamorphs from LPTA, ISP, and SSP were
      smaller and showed signs of emaciation by the end of the experiment. Statistical
      comparisons showed that the proportions of each type of morphological
      abnormalities (swollen bodies and diamond shape, gut uncoiling, diverted gut,
      stiff tails, polydactyly, and visceral and hindlimb hemorrhaging) were
      significantly greater in metal- and nutrient-rich sediment treatments. Moreover,
      activities of BChE, GST and CAT, as well as and presence of micronuclei,
      immature, mitotic, anucleated erythrocytes varied significantly among treatments.
      Our biological effects-based sediment study highlights the use of different
      biological endpoints and biomarkers on anuran larvae at sites where pond sediment
      is risky and sediment management should be considered. Finally, the information
      of those biological endpoints and biomarkers would be useful as a management tool
      to decide if there are sufficient exposures of tadpoles to suspected pollutants
      on sediment. 

PMID- 24080098
TI  - Generating different epigenotypes.
AB  - Embryonic development is a specificity of metazoans. It starts with fertilization
      of the oocyte by a spermatozoon. Gametes then undergo intense chromatin
      remodelling and epigenetic reprogramming, which is necessary for reversion to a
      totipotent state in order to start a new developmental programme. This
      reprogramming process must occur with 100% efficiency in order to sustain
      development. The period following fertilization is therefore very rich and
      interesting in terms of chromatin remodelling. The latter underlies the
      reprogramming of the parental genomes, which is thought in turn to be essential
      to achieve the plasticity required to form all cell types in the new organism.
      However, this amazing capacity of the cells in the embryo to generate all cell
      types seems to be transient. Indeed, the ability of the early embryo to
      reprogramme somatic nuclei decreases as development proceeds. What makes the
      cells in the early embryo capable of supporting such a large degree of
      plasticity? These questions have remained largely unanswered and are central for
      understanding of cell plasticity, development and reprogramming. It is proposed
      that the basis of such plasticity relies on distinctive chromatin features that
      prevail during early embryogenesis and this hypothesis will be discussed in light
      of recent findings.

PMID- 24080099
TI  - Progenitor cell release plus exercise to improve functional performance in
      peripheral artery disease: the PROPEL Study.
AB  - Functional impairment, functional decline, and mobility loss are major public
      health problems in people with lower extremity peripheral artery disease (PAD).
      Few medical therapies significantly improve walking performance in PAD. We
      describe methods for the PROgenitor cell release Plus Exercise to improve
      functionaL performance in PAD (PROPEL) Study, a randomized controlled clinical
      trial designed to determine whether granulocyte-macrophage colony stimulating
      factor (GM-CSF) combined with supervised treadmill walking exercise improves six
      minute walk distance more than GM-CSF alone, more than supervised treadmill
      exercise alone, and more than placebo plus attention control in participants with
      PAD, respectively. PROPEL Study participants are randomized to one of four arms
      in a 2 by 2 factorial design. The four study arms are GM-CSF plus supervised
      treadmill exercise, GM-CSF plus attention control, placebo plus supervised
      exercise therapy, or placebo plus attention control. The primary outcome is
      change in six-minute walk distance at 12-week follow-up. Secondary outcomes
      include change in brachial artery flow-mediated dilation (FMD), change in maximal
      treadmill walking time, and change in circulating CD34+ cells at 12-week follow
      up. Outcomes are also measured at six-week and six-month follow-up. Results of
      the PROPEL Study will have important implications for understanding mechanisms of
      improving walking performance and preventing mobility loss in the large and
      growing number of men and women with PAD. 

PMID- 24080101
TI  - New non-symmetrical choline kinase inhibitors.
AB  - Identification of novel and selective anticancer agents remains an important and
      challenging goal in pharmacological research. Choline kinase (ChoK) is the first
      enzyme in the CDP-choline pathway that synthesizes phosphatidylcholine (PC), the
      major phospholipid in eukaryotic cell membranes. In the present paper, a new
      family of non-symmetrical monocationic compounds is developed including a 3
      aminophenol moiety, bound to 4-(dimethylamino)- or 4-(pyrrolidin-1-yl)pyridinium
      cationic heads through several linkers. The most promising compounds in these
      series as ChoK inhibitors are 3f and 4f, while compounds 3c, 3d and 4c are the
      better antiproliferative agents. The analysis of the biological data observed in
      the described series of compounds mays represents a platform for the design of
      more active molecules. 

PMID- 24080102
TI  - CoMFA studies and in vitro evaluation of some 3-substituted benzylthio
      quinolinium salts as anticryptococcal agents.
AB  - The 3-dimensional quantitative structure-activity relationship (3D-QSAR)
      molecular modeling technique or comparative molecular field analysis (CoMFA) has
      been used to design analogs of the natural product cryptolepine (1). Twenty-three
      compounds with their in vitro biological activities (IC50 values) against
      Crytococcus neoformans were used to generate the training set database of
      compounds for the CoMFA studies. The cross-validated q(2), noncross-validated
      r(2), and partial least squares (PLS) analysis results were used to predict the
      biological activity of 11 newly designed test set compounds. The best CoMFA model
      produced a q(2) of 0.815 and an r(2) of 0.976 indicating high statistical
      significance as a predictive model. The steric and electrostatic contributions
      from the contour map were interpreted from the color-coded contour plots
      generated from the PLS model and the active structural components for potency
      against C. neoformans were determined and validated in the test set compounds.
      The 3-substituted benzylthio quinolinium salts (4) that make up the test set were
      synthesized and evaluated based on the predicted activity from the CoMFA model
      and the results produced a good correlation between the predicted and
      experimental activity (R=0.82). Thus, CoMFA has served as an effective tool to
      aid the design of new analogs and in this case, it has aided the identification
      of compounds equipotent with amphotericin B, the gold standard in antifungal drug
      design. 

PMID- 24080103
TI  - Targeting the human parasite Leishmania donovani: discovery of a new promising
      anti-infectious pharmacophore in 3-nitroimidazo[1,2-a]pyridine series.
AB  - We report herein the discovery of antileishmanial molecules based on the
      imidazo[1,2-a]pyridine ring. In vitro screenings of imidazopyridines belonging to
      our chemical library, toward the promastigotes stage of Leishmania donovani,
      J774A.1 murine and HepG2 human cells, permitted to identify three selective hit
      compounds (12, 20 and 28). New derivatives were then synthesized to allow
      structure-activity and -toxicity relationships analyses, enabling to characterize
      a lead-compound (44) displaying both a high potency (IC50=1.8 MUM) and a good
      selectivity index, in comparison with three antileishmanial reference drug
      compounds (amphotericin B, miltefosine and pentamidine). Moreover, lead-compound
      44 also exhibits good in vitro activity against the intracellular amastigote
      stage of L. donovani. Thus, the 6-halo-3-nitro-2
      (phenylsulfonylmethyl)imidazo[1,2-a]pyridine scaffold appears as a new promising
      selective antileishmanial pharmacophore, especially when substituted at position
      8 by a bromine atom.

PMID- 24080104
TI  - Cynaropicrin targets the trypanothione redox system in Trypanosoma brucei.
AB  - In mice cynaropicrin (CYN) potently inhibits the proliferation of Trypanosoma
      brucei-the causative agent of Human African Trypanosomiasis-by a so far unknown
      mechanism. We hypothesized that CYNs alpha,beta-unsaturated methylene moieties
      act as Michael acceptors for glutathione (GSH) and trypanothione (T(SH)2), the
      main low molecular mass thiols essential for unique redox metabolism of these
      parasites. The analysis of this putative mechanism and the effects of CYN on
      enzymes of the T(SH)2 redox metabolism including trypanothione reductase,
      trypanothione synthetase, glutathione-S-transferase, and ornithine decarboxylase
      are shown. A two step extraction protocol with subsequent UPLC-MS/MS analysis was
      established to quantify intra-cellular CYN, T(SH)2, GSH, as well as GS-CYN and
      T(S-CYN)2 adducts in intact T. b. rhodesiense cells. Within minutes of exposure
      to CYN, the cellular GSH and T(SH)2 pools were entirely depleted, and the
      parasites entered an apoptotic stage and died. CYN also showed inhibition of the
      ornithine decarboxylase similar to the positive control eflornithine. Significant
      interactions with the other enzymes involved in the T(SH)2 redox metabolism were
      not observed. Alongside many other biological activities sesquiterpene lactones
      including CYN have shown antitrypanosomal effects, which have been postulated to
      be linked to formation of Michael adducts with cellular nucleophiles. Here the
      interaction of CYN with biological thiols in a cellular system in general, and
      with trypanosomal T(SH)2 redox metabolism in particular, thus offering a
      molecular explanation for the antitrypanosomal activity is demonstrated. At the
      same time, the study provides a novel extraction and analysis protocol for
      components of the trypanosomal thiol metabolism. 

PMID- 24080105
TI  - Antiproliferative, antiandrogenic and cytotoxic effects of novel caffeic acid
      derivatives in LNCaP human androgen-dependent prostate cancer cells.
AB  - Caffeic acid and its naturally occurring derivative caffeic acid phenethyl ester
      (CAPE) have antiproliferative and cytotoxic properties in a variety of cancer
      cell lines without displaying significant toxicity toward healthy cells, and are
      considered to be potential anticancer agents. However, little is known about
      their effects on prostate cancer cells. We synthesized and evaluated the effects
      of caffeic acid, CAPE (2) and 18 synthetic derivatives on cell viability and
      androgen-dependent cell proliferation, subcellular localisation and expression of
      androgen receptor (AR) and secretion of prostate-specific antigen (PSA) in LNCaP
      human hormone-dependent prostate cancer cells. Several synthetic derivatives of
      CAPE were strong, concentration-dependent cytotoxic agents in LNCaP cells with
      IC50 values in the 6.8-26.6 MUM range, potencies that were up to five-fold
      greater than that of CAPE (33.7+/-4.0 MUM). A number of caffeic acid derivatives
      were inhibitors of androgen-stimulated LNCaP cell proliferation with concomitant
      inhibition of DHT-stimulated PSA secretion. Compound 24 was the most cytotoxic
      and antiproliferative caffeic acid derivative (IC50 values of 6.8+/-0.3 and 2.4+/
      0.8 MUM, respectively) inhibiting DHT-stimulated cell proliferation and PSA
      secretion statistically significantly at concentrations as low as 0.3 MUM.
      Exposure to DHT increased cytoplasmic and nuclear AR levels and co-treatment with
      increasing concentrations of compound 24 or CAPE (2), notably, further increased
      these levels. In conclusion, a number of synthetic derivatives of caffeic acid
      are potent inhibitors of androgen-dependent prostate cancer cell proliferation
      and viability, acting, at least in part, via an antiandrogenic mechanism that
      involves increased nuclear accumulation of (presumably inactive) AR.

PMID- 24080106
TI  - Chemicals from coal coking.

PMID- 24080100
TI  - Design features of the Diabetes and Periodontal Therapy Trial (DPTT): a
      multicenter randomized single-masked clinical trial testing the effect of
      nonsurgical periodontal therapy on glycosylated hemoglobin (HbA1c) levels in
      subjects with type 2 diabetes and chronic periodontitis.
AB  - BACKGROUND: Evidence suggests that periodontitis is associated with prevalent and
      incident type 2 diabetes mellitus (T2DM), raising the question of whether
      periodontitis treatment may improve glycemic control in patients with T2DM. Meta
      analyses of mostly small clinical trials suggest that periodontitis treatment
      results in a modest reduction in glycosylated hemoglobin (Hb) A1c. PURPOSE: The
      purpose of the Diabetes and Periodontal Therapy Trial (DPTT) was to determine if
      periodontal treatment reduces HbA1c in patients with T2DM and periodontitis.
      METHODS: DPTT was a phase-III, single-masked, multi-center, randomized trial with
      a planned enrollment of 600 participants. Participants were randomly assigned to
      receive periodontal treatment immediately (Treatment Group) or after 6 months
      (Control Group). HbA1c values and clinical periodontal measures were determined
      at baseline and 3 and 6 months following randomization. Medication usage and
      dosing were assessed at each visit. Periodontal treatment consisted of scaling
      and root planing for a minimum of two 90-minute sessions, plus the use of an
      antibacterial mouth rinse for at least 32 days afterwards. The primary outcome
      was change in HbA1c from baseline to 6 months and the trial was powered to detect
      a between-group difference of 0.6%. Secondary outcomes included changes in
      periodontal clinical measures, fasting plasma glucose, the Homeostasis Model
      Assessment (HOMA2) and the need for rescue diabetes or periodontal therapy.
      CONCLUSION: Dental and medical researchers collaborated to recruit, treat and
      monitor participants with two chronic diseases to determine if treatment of one
      condition affects the status of the other.

PMID- 24080108
TI  - Coronary thrombosis from large, nonprotruding, superficial calcified coronary
      plaques.

PMID- 24080107
TI  - Validity of the surface electrocardiogram criteria for right ventricular
      hypertrophy: the MESA-RV Study (Multi-Ethnic Study of Atherosclerosis-Right
      Ventricle).
AB  - OBJECTIVES: The study aimed to assess the diagnostic properties of
      electrocardiographic (ECG) criteria for right ventricular hypertrophy (RVH)
      measured by cardiac magnetic resonance imaging (cMRI) in adults without clinical
      cardiovascular disease. BACKGROUND: Current ECG criteria for RVH were based on
      cadaveric dissection in small studies. METHODS: MESA (Multi-Ethnic Study of
      Atherosclerosis) performed cMRIs with complete right ventricle (RV)
      interpretation on 4,062 participants without clinical cardiovascular disease.
      Endocardial margins of the RV were manually contoured on diastolic and systolic
      images. The ECG screening criteria for RVH from the 2009 American Heart
      Association Recommendations for Standardization and Interpretation of the ECG
      were examined in participants with and without left ventricular (LV) hypertrophy
      or reduced ejection fraction. RVH was defined using sex-specific normative
      equations based on age, height, and weight. RESULTS: The study sample with normal
      LV morphology and function (n = 3,719) was age 61.3 +/- 10.0 years, 53.5% female,
      39.6% Caucasian, 25.5% African American, 21.9% Hispanic, and 13.0% Asian. The
      mean body mass index was 27.9 +/- 5.0 kg/m(2). A total of 6% had RVH, which was
      generally mild. Traditional ECG criteria were specific (many >95%) but had low
      sensitivity for RVH by cMRI. The positive predictive values were not sufficiently
      high as to be clinically useful (maximum 12%). The results did not differ based
      on age, sex, race, or smoking status, or with the inclusion of participants with
      abnormal LV mass or function. Classification and regression tree analysis
      revealed that no combination of ECG variables was better than the criteria used
      singly. CONCLUSIONS: The recommended ECG screening criteria for RVH are not
      sufficiently sensitive or specific for screening for mild RVH in adults without
      clinical cardiovascular disease.

PMID- 24080109
TI  - Pulmonary valve replacement after operative repair of tetralogy of Fallot: meta
      analysis and meta-regression of 3,118 patients from 48 studies.
AB  - Because the real benefit of pulmonary valve replacement (PVR) in patients with
      repaired tetralogy of Fallot who develop pulmonary insufficiency remains unclear,
      it is necessary to analyze the evidence published around the world. We performed
      a systematic review of studies that reported data about the effect of PVR in
      patients with repaired tetralogy of Fallot that developed pulmonary
      insufficiency, until December 2012. The variables chosen to represent the benefit
      were both right ventricular (RV) and left ventricular measures, QRS duration, and
      functional class. The principal summary measures were difference in means with
      95% confidence interval and p values (considered statistically significant when p
      < 0.05). The differences in means were combined across studies with the weighted
      DerSimonian-Laird random effects model. Meta-analysis, sensitivity analysis, and
      meta-regression were completed with the software Comprehensive Meta-Analysis
      (version 2, Biostat, Inc., Englewood, New Jersey). Forty-eight studies involving
      3,118 patients met the eligibility criteria. The pooled 30-day mortality was
      0.87% (47 studies; 27 of 3,100 patients); the pooled 5-year mortality was 2.2%
      (24 studies; 49 of 2,231 patients); the pooled 5-year re-PVR was 4.9% (15
      studies; 88 of 1,798 patients). The results of this meta-analysis demonstrate
      that after PVR: 1) the RV experiences improvement of its volumes and function; 2)
      the left ventricle experiences improvement of its function; 3) QRS duration
      decreases; 4) symptoms improve; 5) pre-operative RV geometry modulates the effect
      of PVR; and 6) there is important heterogeneity of the effects among the studies,
      and few publication biases. In conclusion, PVR seems to be a positive approach in
      the analyzed scenario.

PMID- 24080111
TI  - Massive left ventricular pseudoaneurysm 20 years after acute myocardial
      infarction.

PMID- 24080110
TI  - Adoption and effectiveness of internal mammary artery grafting in coronary artery
      bypass surgery among Medicare beneficiaries.
AB  - OBJECTIVES: The aim of this study was to assess the pattern of the adoption of
      internal mammary artery (IMA) grafting in the United States, test its association
      with clinical outcomes, and assess whether its effectiveness differs in key
      clinical subgroups. BACKGROUND: The effect of IMA grafting on major clinical
      outcomes has never been tested in a large randomized trial, yet it is now a
      quality standard for coronary artery bypass graft (CABG) surgery. METHODS: We
      identified Medicare beneficiaries >=66 years of age who underwent isolated
      multivessel CABG between 1988 and 2008, and we documented patterns of IMA use
      over time. We used a multivariable propensity score to match patients with and
      without an IMA and compared rates of death, myocardial infarction (MI), and
      repeat revascularization. We tested for variations in IMA effectiveness with
      treatment * covariate interaction tests. RESULTS: The IMA use in CABG rose slowly
      from 31% in 1988 to 91% in 2008, with persistent wide geographic variations.
      Among 60,896 propensity score-matched patients over a median 6.8-year follow-up,
      IMA use was associated with lower all-cause mortality (adjusted hazard ratio:
      0.77, p < 0.001), lower death or MI (adjusted hazard ratio: 0.77, p < 0.001), and
      fewer repeat revascularizations over 5 years (8% vs. 9%, p < 0.001). The
      association between IMA use and lower mortality was significantly weaker (p <=
      0.008) for older patients, women, and patients with diabetes or peripheral
      arterial disease. CONCLUSIONS: Internal mammary artery grafting was adopted
      slowly and still shows substantial geographic variation. IMA use is associated
      with lower rates of death, MI, and repeat coronary revascularization.

PMID- 24080112
TI  - Single cell tracking of gadolinium labeled CD4+ T cells by laser ablation
      inductively coupled plasma mass spectrometry.
AB  - Cellular therapy is emerging as a promising alternative to conventional
      immunosuppression in the fields of hematopoietic stem cell (HSC) transplantation,
      autoimmune disease, and solid organ transplantation. Determining the persistence
      of cell-based therapies in vivo is crucial to understanding their regulatory
      function and requires the combination of an extremely sensitive detection
      technique and a stable, long-lifetime cell labeling agent. This paper reports the
      first application of laser ablation inductively coupled plasma mass spectrometry
      (LA-ICP-MS) to perform single cell detection of T cell populations relevant to
      cellular immunotherapy. Purified human CD4(+) T cells were labeled with
      commercially available Gd-based magnetic resonance imaging (MRI) contrast agents,
      Omniscan and Dotarem, which enabled passive loading of up to 10(8) Gd atoms per
      cell. In mixed preparations of labeled and unlabeled cells, LA-ICP-MS was capable
      of enumerating labeled cells at close to the predicted ratio. More importantly,
      LA-ICP-MS single cell analysis demonstrated that the cells retained a sufficient
      label to remain detectable for up to 10 days post-labeling both in vitro and in
      vivo in an immunodeficient mouse model. 

PMID- 24080113
TI  - New evidence for the involvement of Paracartia grani (Copepoda, Calanoida) in the
      life cycle of Marteilia refringens (Paramyxea).
AB  - The dynamics of the protozoan parasite Marteilia refringens was studied in Thau
      lagoon, an important French shellfish site, for 1 year in three potential hosts:
      the Mediterranean mussel Mytilus galloprovincialis (Mytiliidae), the grooved
      carpet shell Ruditapes decussatus (Veneriidae) and the copepod Paracartia grani
      (Acartiidae). Parasite DNA was detected by PCR in R. decussatus. In situ
      hybridisation showed necrotic cells of M. refringens in the digestive epithelia
      of some R. decussatus suggesting the non-involvement of this species in the
      parasite life cycle. In contrast, the detection of M. refringens in mussels using
      PCR appeared bimodal with two peaks in spring and autumn. Histological
      observations of PCR-positive mussels revealed the presence of different parasite
      stages including mature sporangia in spring and autumn. These results suggest
      that the parasite has two cycles per year in the Thau lagoon and that mussels
      release parasites into the water column during these two periods. Moreover, PCR
      detection of the parasite in the copepodid stages of P. grani between June and
      November supports the hypothesis of the transmission of the parasite from mussels
      to copepods and conversely. In situ hybridisation performed on copepodites showed
      labeling in some sections. Unusual M. refringens cells were observed in the
      digestive tract and the gonad from the third copepodid stage, suggesting that the
      parasite could infect a copepod by ingestion and be released through the gonad.
      This hypothesis is supported by the PCR detection of parasite DNA in copepod eggs
      from PCR-positive females, which suggests that eggs could contribute to the
      parasite spreading in the water and could allow overwintering of M. refringens.
      Finally, in order to understand the interactions between mussels and copepods,
      mussel retention efficiency (number of copepods retained by a mussel) was
      measured for all P. grani developmental stages. Results showed that all copepod
      stages could contribute to the transmission of the parasite, especially eggs and
      nauplii which were retained by up to 90%.

PMID- 24080114
TI  - To perform operative procedures in an optimized local atmosphere: can it reduce
      post-operative adhesion formation?
AB  - BACKGROUND: Adhesion formation is a major problem following abdominal surgery as
      it creates a considerable economic burden in addition to an increased risk for
      complications. In the present study, an effort was made to reduce post-operative
      adhesion formation by creating an artificial atmosphere within and around the
      abdominal cavity during an open surgical procedure. METHODS: 82 Wistar male rats
      (Clr:WI) (200 gr, 7 weeks) were randomized into two groups. The abdominal cavity
      of the control group was exposed to the normal atmosphere of the operating
      theatre during surgery (21% O2, 21  degrees C, 40-47% relative humidity (RH)),
      while the abdominal cavity of the study group was exposed to an artificial
      atmosphere during surgery (3-6% O2, >75% CO2, 95-100% RH, 37  degrees C).
      Adhesion induction consisted of a laparotomy along linea-alba, four lesions in
      the anterior abdominal-wall, blood from the tail vein dripped inside the
      abdominal cavity and exposure to the atmosphere around the wound by use of self
      retaining retractors. In addition, a liquid-sample for quantitative bacteriologic
      cultivation and bacterial load (CFU/ml) calculation was taken just before
      closure. After 3 weeks the abdominal cavity was scored for the extent, tenacity
      and severity of adhesions before the rats were euthanized. The two-sample
      Wilcoxon-rank-sum test was used in the analysis. RESULTS: Highly significant
      differences in postoperative total adhesion score, extent-, severity- and
      tenacity-score were found (P < 0.01). No differences were found between the two
      groups regarding mean bacterial load (P > 0.05). CONCLUSIONS: The rats exposed to
      the warmed and humidified artificial atmosphere consisting of more than 75%
      carbon dioxide and 3-4% oxygen during surgery had more severe and more post
      operative adhesions compared to the rats that were exposed to the ambient air
      during surgery.

PMID- 24080115
TI  - Bilirubin; a diagnostic marker for appendicitis.
AB  - INTRODUCTION: Every investigation that can contribute towards a diagnosis of
      appendicitis is valuable to the emergency general surgeon. Previous research has
      suggested that hyperbilirubinaemia is a more specific marker for both simple and
      perforated appendicitis than WBC (white blood count) and CRP (C-reactive
      protein), but this investigation is not commonly used to help diagnose
      appendicitis. AIMS: This study investigated whether there is an association
      between hyperbilirubinaemia and appendicitis. We also reviewed the diagnostic
      value of bilirubin in perforated vs simple appendicitis, and compared it with the
      serum C-reactive protein (CRP) and white blood cell count (WBC). METHODS: This
      single centre, prospective observational study included all patients admitted
      with right iliac fossa (RIF) pain who had liver function tests performed.
      Statistical analysis was performed using Fisher's exact test to compare
      bilirubin, WBC and CRP levels for normal appendices, simple appendicitis, and
      perforated appendicitis. RESULTS: 242 patients were included in this study, of
      whom 143 were managed operatively for RIF pain. Hyperbilirubinaemia was
      significantly associated with appendicitis vs RIF pain of other aetiologies (p <
      0.0001). Bilirubin had a higher specificity (0.96), than WBC (0.71) and CRP
      (0.62), but a lower sensitivity (0.27 vs 0.68 and 0.82 respectively).
      Hyperbilirubinaemia was associated with perforated appendicitis vs simple
      appendicitis with statistical significance (p < 0.0001). Bilirubin had a higher
      specificity (0.82) than both WBC (0.34) and CRP (0.21), but a lower sensitivity
      (0.70 vs 0.80 and 0.95 respectively). CONCLUSION: Our findings confirm that
      hyperbilirubinaemia has a high specificity for distinguishing acute appendicitis,
      especially when perforated, from other causes of RIF pain, particularly those not
      requiring surgery.

PMID- 24080116
TI  - Burden of disease in treated rheumatoid arthritis patients: going beyond the
      joint.
AB  - OBJECTIVE: The disease burden in rheumatoid arthritis (RA) extends beyond the
      joint. This article evaluates the physical and psychosocial extra-articular
      burden of treated RA and relationships among diverse disease manifestations.
      METHODS: MEDLINE searches identified papers published in English from January
      2003 to December 2012 that evaluated systemic complications and psychosocial
      aspects associated with RA. Preference was given to studies with randomized
      cohorts and large (>100) sample sizes. Of 378 articles identified in the initial
      search, 118 were selected for inclusion. RESULTS: RA is associated with multiple
      comorbidities and psychosocial impairments, including cardiovascular disease,
      osteoporosis, interstitial lung disease, infection, malignancies, fatigue,
      depression, cognitive dysfunction, reduced work performance, work disability, and
      decreased health-related quality of life. The etiology of the extra-articular
      burden may reflect the systemic inflammation and immune system alteration
      associated with RA, metabolic imbalances and side effects related to treatment,
      or the influence of comorbidities. Strategies that may help to reduce the extra
      articular disease burden include personalized medicine and the potential
      introduction of treatments with new mechanisms of action. CONCLUSION: Despite
      improvements in treating joint disease, the extra-articular burden in RA remains
      substantial, encompassing multiple comorbidities and psychosocial impairments.

PMID- 24080117
TI  - Analysis of intradiscal cement leakage during percutaneous vertebroplasty:
      multivariate study of risk factors emphasizing preoperative MR findings.
AB  - OBJECTIVE: Previous reports have shown that intradiscal cement leakage during
      percutaneous vertebroplasty (PVP) is related to several risk factors. The purpose
      of this study was to evaluate preoperative MRI scans for such risk factors.
      METHODS: The study retrospectively analyzed 136 patients (aged 43-93 years; 234
      vertebral bodies) with osteoporotic compression fractures. All patients underwent
      both MRI and PVP. There were 28 men (20.59%) and 108 women (79.41%). Age, gender,
      bone mineral density (BMD) score, endplate cortical disruption, abnormal T2
      weighted hyperintensity in adjacent discs, presence of Kummell's disease, linear
      body fracture with extension to endplate, level of treated vertebral body and
      injected cement volume were considered risk factors for intradiscal cement
      leakage. RESULTS: Of the 234 vertebral bodies, 55 bodies from 42 patients with no
      endplate cortical disruption showed no adjacent intradiscal cement leakage. Of
      179 bodies from 95 patients with endplate cortical disruption, 54 (30.17%) showed
      intradiscal cement leakage. Of the other possible risk factors, abnormal T2
      hyperintensity in adjacent discs was significantly related to intradiscal cement
      leakage (P = 0.016). The other possible factors (age, gender, BMD score,
      Kummell's disease, linear body fracture extending to the endplate, level of
      treated vertebral body and injected cement volume) were not related to
      intradiscal cement leakage. CONCLUSION: There was no adjacent intradiscal cement
      leakage without endplate cortical disruption. Abnormal T2 hyperintensity in
      adjacent discs may be related to intradiscal cement leakage, but only in the
      presence of endplate cortical disruption. Also, not having Kummell's disease did
      not prevent intradiscal cement leakage. Thus, given these circumstances, careful
      cement injection is needed to reduce intradiscal cement leakage.

PMID- 24080118
TI  - Bioinspired in situ growth of conversion films with underwater superoleophobicity
      and excellent self-cleaning performance.
AB  - Wax deposition during the production and transportation of crude oil is a global
      problem in oil industries. Fabrication of underwater self-cleaning materials can
      provide a new strategy to prohibit wax deposition. In this paper, conversion
      films on carbon steel with hierarchical micro/nanostructure are fabricated
      through a novel in situ alternating-current deposition method. The flower-like
      conversion films are composed of amorphous iron phosphate and present
      superhydrophilicity in air and superoleophobicity underwater. The conversion
      films can efficiently prevent the deposition of wax in water-contained crude oil,
      showing excellent self-cleaning performance. This facile and low-cost fabrication
      of a self-cleaning film provides a good strategy for underwater-oil prevention. 

PMID- 24080119
TI  - On the use of L-012, a luminol-based chemiluminescent probe, for detecting
      superoxide and identifying inhibitors of NADPH oxidase: a reevaluation.
AB  - L-012, a luminol-based chemiluminescent (CL) probe, is widely used in vitro and
      in vivo to detect NADPH oxidase (Nox)-derived superoxide (O2(*-)) and identify
      Nox inhibitors. Yet understanding of the free radical chemistry of the L-012
      probe is still lacking. We report that peroxidase and H2O2 induce superoxide
      dismutase (SOD)-sensitive, L-012-derived CL in the presence of oxygen. O2(*-)
      alone does not react with L-012 to emit luminescence. Self-generated O2(*-)
      during oxidation of L-012 and luminol analogs artifactually induce CL inhibitable
      by SOD. These aspects make assays based on luminol analogs less than ideal for
      specific detection and identification of O2(*-) and NOX inhibitors.

PMID- 24080120
TI  - Cyclic di-GMP mediates Mycobacterium tuberculosis dormancy and pathogenecity.
AB  - Dormancy of Mycobacterium tuberculosis is likely to be a major cause of extended
      chemotherapeutic regimens and wide prevalence of tuberculosis. The molecular
      mechanisms underlying M. tuberculosis dormancy are not well understood. In this
      study, single-copy genes responsible for synthesis (dgc) and degradation (pde) of
      the ubiquitous bacterial second messenger, cyclic di-GMP (c-di-GMP), were deleted
      in the virulent M. tuberculosis strain H37Rv to generate dgc(mut) and Deltapde,
      respectively. Under aerobic growth conditions, the two mutants and wild-type
      cells showed similar phenotypes. However, dgc(mut) and Deltapde exhibited
      increased and reduced dormancy, respectively, in both anaerobiosis-triggered and
      vitamin C-triggered in vitro dormancy models, as determined by survival and
      growth recovery from dormancy. The transcriptomes of aerobic cultures of dgc(mut)
      and wild-type H37Rv exhibited no difference, whereas those of anaerobic cultures
      showed a significant difference with 61 genes that are not a part of the dosR
      regulon. Furthermore, Deltapde but not dgc(mut) showed decreased infectivity with
      human THP-1 cells. Deltapde also showed attenuated pathogenicity in a C57BL/6
      mouse infection model. These findings are explained by c-di-GMP-mediated
      signaling negatively regulating M. tuberculosis dormancy and pathogenicity. 

PMID- 24080121
TI  - Molecular characterization of Mycobacterium bovis isolates from pastoral
      livestock at Mikumi-Selous ecosystem in the eastern Tanzania.
AB  - Domestic ruminants and Wild ungulates can act as reservoir hosts for
      Mycobacterium bovis, causative agent for bovine tuberculosis (BTB) in animals and
      man. Bovine tuberculosis (BTB) is endemic in pastoral livestock in Tanzania.
      There is lack of information on genotypic distribution of M. bovis in animals at
      wildlife-livestock interface areas and in wildlife conserved areas. The
      objectives of this study were to characterize and determine the spatial
      distribution of M. bovis isolates. Tissue samples from cattle and wildlife were
      cultured and analyzed using deletion typing and spoligotyping techniques. Eight
      (8.9%) M. bovis strains were isolated from cattle and confirmed by RD4 and RD9
      polymerize chain reaction (PCR) assays. Spoligotype SB1467 was the dominant
      pattern 62.5% (n = 8) in infected animals, two isolates belonged to a newly
      reported type SB2190, and one isolate belonged to SB0133. The spoligotype
      patterns of SB1467 and SB0133 were closely related (96.9%) while SB2190 was less
      related (59.4%) to SB0133, the relatedness amongst spoligotypes were associated
      with spacer position 15. No M. bovis was isolated from hunted wild animals. The
      current study has identified a novel spoligotype SB2190. The current data suggest
      that wild animals in Mikumi-Selous ecosystem are at risk of acquiring M. bovis
      infection due to occasional interaction by sharing of pasture and water sources
      between wildlife and livestock. Integrated efforts by all stakeholders are
      crucial for controlling spread of tuberculosis at livestock/wildlife/human
      interface areas. 

PMID- 24080122
TI  - Treatment receipt and outcomes among lung cancer patients with depression.
AB  - AIMS: Among lung cancer patients, depression has been associated with increased
      mortality, although the mechanisms are unknown. We evaluated the association of
      depression with mortality and receipt of cancer therapies among depressed
      veterans with lung cancer. MATERIALS AND METHODS: A retrospective, cohort study
      of lung cancer patients in the Veterans Affairs-Northwest Health Network from
      1995 to 2010. Depression was defined by ICD-9 coding within 24 months before lung
      cancer diagnosis. Multivariable Cox proportional analysis and logistic regression
      were used. RESULTS: In total, 3869 lung cancer patients were evaluated; 14% had a
      diagnosis of depression. A diagnosis of depression was associated with increased
      mortality among all stage lung cancer patients (hazard ratio = 1.14, 95%
      confidence interval: 1.03-1.27, P = 0.01). Among early-stage (I and II) non-small
      cell lung cancer (NSCLC) patients, the hazard ratio was 1.37 (95% confidence
      interval: 1.12-1.68, P = 0.003). There was no association of depression diagnosis
      with surgery (odds ratio = 0.83, 95% confidence interval: 0.56-1.22, P = 0.34)
      among early-stage NSCLC patients. A depression diagnosis was not associated with
      mortality (hazard ratio = 1.02, 95% confidence interval: 0.89-1.16, P = 0.78) or
      chemotherapy (odds ratio = 1.07, 95% confidence interval: 0.83-1.39, P = 0.59) or
      radiation (odds ratio = 1.04, 95% confidence interval: 0.81-1.34, P = 0.75)
      receipt among advanced-stage (III and IV) NSCLC patients. Increased utilisation
      of health services for depression was associated with increased mortality among
      depressed patients. CONCLUSIONS: Depression is associated with increased
      mortality in lung cancer patients and this association is higher among those with
      increased measures of depression care utilisation. Differences in lung cancer
      treatment receipt are probably not responsible for the observed mortality
      differences between depressed and non-depressed patients. Clinicians should
      recognise the significant effect of depression on lung cancer survival.

PMID- 24080123
TI  - Simultaneous pyrosequencing of the 16S rRNA, IncP-1 trfA, and merA genes.
AB  - The use of amplicon pyrosequencing makes it possible to produce thousands of
      sequences of the same gene at relatively low costs. Here we show that it is
      possible to simultaneously sequence the 16S rRNA gene, IncP-1 trfA gene and
      mercury reductase gene (merA) as a way for screening the diversity of several
      genes in the same samples. As a proof-of-concept two different soil samples and a
      wastewater sample were screened. Multiplexing identifiers (MIDs) and sequencing
      adapters were added to amplicons using a tailed PCR approach and the universal
      overhangs U1 and U2 for this approach were redesigned. Furthermore, this is the
      first time the IncP-1 plasmid diversity was studied by amplicon pyrosequencing
      and for this purpose a clustering threshold of 89% nucleotide sequence similarity
      was determined to differentiate the IncP-1 subgroups. 

PMID- 24080124
TI  - The cultural adaptation and validation of a Swedish version of the satisfaction
      with appearance scale (SWAP-Swe).
AB  - BACKGROUND: Body image dissatisfaction is a source of stress after burns and it
      is important to attempt to objectively measure this aspect. Unfortunately, there
      are no Swedish questionnaires to assess satisfaction of appearance after burns.
      AIM: The aim of this study was to translate, culturally adapt and validate the
      Satisfaction With Appearance Scale (SWAP) into Swedish from American English to
      be used in the context of burn care. METHOD: The SWAP was translated and cross
      cultural adapted inspired by the guidelines by Guillemin. Pre-testing with 13
      burn patients was conducted and 90 patients tested the questionnaire in order to
      determine its psychometric properties. RESULTS: Cronbach's alpha was 0.89
      indicating a high level of internal consistency of Swedish SWAP. Test for
      construct validity showed that length of hospital stay, more severe burns and
      female gender generated significantly higher scores in SWAP-Swe. The principal
      components analysis found similar subscales according to the original SWAP that
      together accounted for 68% of the total variance. CONCLUSIONS: SWAP-Swe is a
      reliable and valid instrument for use in a Swedish speaking population. The
      questionnaire was perceived to be relevant for usage in the context of burn care
      and is well understood by the patients.

PMID- 24080125
TI  - Thermal biology, population fluctuations and implications of temperature extremes
      for the management of two globally significant insect pests.
AB  - The link between environmental temperature, physiological processes and
      population fluctuations is a significant aspect of insect pest management. Here,
      we explore how thermal biology affects the population abundance of two globally
      significant pest fruit fly species, Ceratitis capitata (medfly) and C. rosa
      (Natal fruit fly), including irradiated individuals and those expressing a
      temperature sensitive lethal (tsl) mutation that are used in the sterile insect
      technique. Results show that upper and lower lethal temperatures are seldom
      encountered at the field sites, while critical minimum temperatures for activity
      and lower developmental thresholds are crossed more frequently. Estimates of
      abundance revealed that C. capitata are active year-round, but abundance declines
      markedly during winter. Temporal autocorrelation of average fortnightly trap
      captures and of development time, estimated from an integrated model to calculate
      available degree days, show similar seasonal lags suggesting that population
      increases in early spring occur after sufficient degree-days have accumulated. By
      contrast, population collapses coincide tightly with increasing frequency of low
      temperature events that fall below critical minimum temperatures for activity.
      Individuals of C. capitata expressing the tsl mutation show greater critical
      thermal maxima and greater longevity under field conditions than reference
      individuals. Taken together, this evidence suggests that low temperatures limit
      populations in the Western Cape, South Africa and likely do so elsewhere.
      Increasing temperature extremes and warming climates generally may extend the
      season over which these species are active, and could increase abundance. The
      sterile insect technique may prove profitable as climates change given that
      laboratory-reared tsl flies have an advantage under warmer conditions. 

PMID- 24080126
TI  - Investigations of the signaling cascade involved in diuretic hormone stimulation
      of Malpighian tubule fluid secretion in Rhodnius prolixus.
AB  - In insects, the excretory system is comprised of the Malpighian tubules (MTs) and
      the hindgut, which collectively function to maintain ionic and osmotic balance of
      the haemolymph and rid the organism of toxic compounds or elements in excess.
      Secretion by the Malpighian tubules of insects is regulated by a variety of
      hormones including peptidergic factors as well as biogenic amines. In Rhodnius
      prolixus, two endogenous diuretic hormones have been identified; the biogenic
      amine serotonin (5-hydroxytryptamine, 5-HT) and the corticotropin releasing
      factor-related peptide, RhoprCRF. Both factors significantly increase secretion
      by MTs and are known to elevate intracellular levels of cAMP. Interestingly,
      applying sub-maximal doses of these two diuretic factors in combination on
      isolated MTs in vitro reveals synergistic effects as rates of fluid secretion are
      significantly higher than would be expected if rates of secretion from MTs
      treated with each factor alone were summed. This observed synergism suggests that
      different downstream targets may be activated by the two diuretic factors, but
      that some cellular elicitors may be shared since cAMP is elevated in response to
      either diuretic hormone. This study investigated the signaling cascade involved
      in the diuretic hormone regulation of Malpighian tubule fluid secretion.
      Bioassays were performed in physiological as well as modified salines (e.g.
      calcium-free) alone or in the presence of a variety of pharmacological compounds
      that interfere with prospective intracellular targets, such as the apical
      cation/H(+) exchanger. Intriguingly, only amiloride yielded differential effects
      on the two diuretics with 5HT-stimulated secretion being blocked, whereas in
      contrast, RhoprCRF-stimulated secretion was unaffected. In addition, experiments
      examining the role of extracellular and intracellular calcium on fluid secretion
      rate showed that both diuretics are dependent on intracellular calcium
      availability. Finally, fluid secretion stimulated by either diuretic hormone was
      also sensitive to inhibition of cAMP-dependent protein kinase A. Taken together,
      these results suggest that each diuretic hormone activates pathways dependent
      upon intracellular calcium and cAMP. 

PMID- 24080127
TI  - Validating common carotid stenosis by duplex ultrasound with carotid angiogram or
      computed tomography scan.
AB  - BACKGROUND: No consensus exists for duplex ultrasound criteria in the diagnosis
      of significant common carotid artery (CCA) stenosis. In general, peak systolic
      velocity (PSV) >150 cm/s with poststenotic turbulence indicates a stenosis >50%.
      The purpose of our study is to correlate CCA duplex velocities with angiographic
      findings of significant stenosis >60%. METHODS: We reviewed the carotid duplex
      records from 2008 to 2011 looking for patients with isolated CCA stenosis and no
      ipsilateral internal or contralateral carotid artery disease who received either
      a carotid angiogram or a computed tomography scan. We identified 25 patients who
      had significant CCA disease >60%. We also selected 74 controls without known CCA
      stenosis. We performed receiver operating characteristics analysis to correlate
      PSV and end-diastolic velocity (EDV) with angiographic stenosis >60%. The degree
      of stenosis was determined by measuring the luminal stenosis in comparison to the
      proximal normal CCA diameter. RESULTS: Most patients had a carotid angiogram
      (21/25), four only had a computed tomography angiography and four had both.
      Eighteen patients had history of neck radiation. The CCA PSV >=250 cm/s had a
      sensitivity of 98.7% (81.5%-100%) and a specificity of 95.7% (92.0%-99.9%), CCA
      PSV >=300 cm/s had a sensitivity of 90.9% (69.4%-98.4%) and a specificity of
      98.7% (92.0%-99.9%). The CCA EDV >=40 cm/s had a sensitivity of 95.5% (95%
      confidence interval of 75.1-99.8%) and specificity of 98.7% (92.0%-99.9%), EDV
      >=60 cm/s had a sensitivity of 100% (75.1%-99.8%) and specificity of 87% (94.1
      100%), and EDV >=70 cm/s had a sensitivity of 86.4% (64.0%-96.4%) and specificity
      of 100% (94.1%-100%). The presence of both PSV <250 cm/s and EDV <60 cm/s had a
      98.7% negative predictive value, and the presence of both PSV >=250 cm/s and EDV
      >=60 cm/s had 100% positive predictive value. CONCLUSIONS: Establishing CCA
      duplex criteria to screen patients with significant stenosis is crucial to
      identify those who will need further imaging modality or treatment. In our
      laboratory, CCA PSV >=250 cm/s and EDV >=60 cm/s are thresholds that can be used
      to identify significant (>60%) CCA stenosis with a high degree of accuracy.

PMID- 24080128
TI  - Discussion.

PMID- 24080129
TI  - A pilot study of regional perfusion and oxygenation in calf muscles of
      individuals with diabetes with a noninvasive measure.
AB  - OBJECTIVE: To assess alterations in the regional perfusion and oxygenation of the
      calf muscles in individuals with diabetes. METHODS: Age-matched individuals with
      (n = 5) and without diabetes (n = 6) were investigated. Skeletal muscle
      perfusion, oxygen extraction fraction, and oxygen consumption rate were measured
      by newly developed noncontrast magnetic resonance imaging (MRI) techniques. The
      subjects lay supine on the MRI table with their foot firmly strapped to a custom
      built isometric exercise device. The measurements were performed at rest and
      during an isometric plantar flexion muscle contraction. RESULTS: Individuals
      without diabetes had up to a 10-fold increase in muscle perfusion, 25% elevation
      in muscle oxygen extraction fraction, and a 12-fold increase in oxygen
      consumption rate in the calf during the plantar flexion isometric contraction. In
      patients with diabetes, the increases in these parameters were only up to
      sixfold, 2%, and sixfold, respectively. Exercise oxygen consumption rate was
      inversely associated with blood HbA1c levels (r(2) = .91). CONCLUSIONS: This is
      the first study to quantify regional skeletal muscle oxygenation in patients with
      diabetes using noncontrast MRI and warrants additional study. Attenuation of
      perfusion and oxygenation during exercise may have implications for understanding
      diabetic complications in the lower extremities.

PMID- 24080130
TI  - Clinical and radiologic course of symptomatic spontaneous isolated dissection of
      the superior mesenteric artery treated with conservative management.
AB  - OBJECTIVE: To determine the clinical and radiological outcomes of patients with
      symptomatic spontaneous isolated dissection of the superior mesenteric artery
      (SIDSMA) who were treated with conservative management. METHODS: This
      retrospective study included 27 consecutive patients who were diagnosed with
      symptomatic SIDSMA and managed conservatively from April 2007 to April 2013.
      Twenty-six patients were treated using anticoagulation therapy, and one patient
      with chronic liver disease underwent observation only. For evaluation, patients
      were divided into two groups, those with a patent false lumen with both entry and
      re-entry (group I), and those with partial or complete thrombosis of the false
      lumen (group II). In general, the patients underwent follow-up computed
      tomography angiography (CTA) 1 week, 1 month, and 6 months after admission.
      Thereafter, they underwent annual CTAs. RESULTS: There were five group I and 22
      group II patients. During hospitalization, none of the patients needed additional
      endovascular or surgical intervention, and after conservative management, every
      patient was asymptomatic upon discharge. The mean duration of clinical follow-up
      was 27.3 months. There was no recurrent abdominal pain associated with SIDSMA,
      and no invasive procedures due to SIDSMA were needed. During a mean of 17.1
      months of CTA follow-up in group I patients, serial CTAs found sustained patent
      false lumen and no angiographic changes in all patients. Among 22 group II
      patients, despite anticoagulation and symptomatic relief, CTA 1 week after
      admission revealed increased stenosis of the true lumen in 84.2% (16/19) of
      patients including six cases of progressive SMA occlusion. Five patients,
      including the three patients initially presenting with SMA occlusion, had no
      interval changes, and only one patient had improved compression of the true
      lumen. During a mean of 18.0 months of CTA follow-up in group II patients, serial
      CTAs revealed improvement in the occlusion or stenosis of the true lumen in 89%
      (16/18) of patients and progressive resolution of false lumen thrombosis in all
      patients. Aneurysmal dilatation greater than 2 cm was not detected in either
      group of patients during follow-up. CONCLUSIONS: During the acute stage of
      SIDSMA, we found a discrepancy between the clinical and angiographic findings.
      The therapeutic regimen should be based on clinical symptoms, and conservative
      management is feasible in most cases. SMA stenosis could not be an indication for
      invasive treatment, because stenosis of the true lumen has been seen to improve
      after the acute stage of dissection.

PMID- 24080131
TI  - Smooth muscle cells from abdominal aortic aneurysms are unique and can
      independently and synergistically degrade insoluble elastin.
AB  - BACKGROUND: The purpose of this study was to further elucidate the role of the
      vascular smooth muscle cells (SMCs) in abdominal aortic aneurysm (AAA) disease.
      We hypothesized that that AAA SMCs are unique and actively participate in the
      process of degrading the aortic matrix. METHODS: Whole-genome expression profiles
      of SMCs from AAAs, nondilated abdominal aorta (NAA), and carotid endarterectomy
      (CEA) were compared. We quantified elastolytic activity by culturing SMCs in
      [(3)H]elastin-coated plates and measuring solubilized tritium in the media after
      7 days. Matrix metalloproteinase (MMP)-2 and MMP-9 production was assessed using
      real-time polymerase chain reaction, zymography, and Western blotting. RESULTS:
      Each SMC type exhibited a unique gene expression pattern. AAA SMCs had greater
      elastolytic activity than NAA-SMCs (+68%; P < .001) and CEA-SMCs (+45%; P <
      .001). Zymography showed an increase of active MMP-2 (62 kD) in media from AAA
      SMCs. AAA SMCs demonstrated twofold greater expression of MMP-2 messenger (m)RNA
      (P < .05) and 7.3-fold greater MMP-9 expression (P < .01) than NAA-SMCs. Culture
      with U937 monocytes caused a synergistic increase of elastolysis by AAA SMCs
      (41%; P < .001) but not NAA-SMCs or CEA-SMCs (P = .99). Coculture with U937
      caused a large increase in MMP-9 mRNA in AAA-SMCs and NAA-SMCs (P < .001). MMP-2
      mRNA expression was not affected. Western blots of culture media showed a
      fourfold increase of MMP-9 (92 kD) protein only in AAA-SMCs/U937 but not in NAA
      SMCs/U937 (P < .001) and a large increase in active-MMP2 (62 kD), which was less
      apparent in NAA-SMCs/U937 media (P < .01). CONCLUSIONS: AAA-SMCs have a unique
      gene expression profile and a proelastolytic phenotype that is augmented by
      macrophages. This may occur by a failure of post-transcriptional control of MMP-9
      synthesis.

PMID- 24080132
TI  - Strategies for prevention of iatrogenic inferior vena cava filter entrapment and
      dislodgement during central venous catheter placement.
AB  - BACKGROUND: Iatrogenic migration of inferior vena cava (IVC) filters is a
      potentially life-threatening complication that can arise during blind insertion
      of central venous catheters when the guide wire becomes entangled with the
      filter. In this study, we reviewed the occurrence of iatrogenic migration of IVC
      filters in the literature and assessed methods for preventing this complication.
      METHODS: A literature search was conducted to identify reports of filter/wire
      entrapment and subsequent IVC filter migration. Clinical outcomes and
      complications were identified. RESULTS: A total of 38 cases of filter/wire
      entrapment were identified. All of these cases involved J-tip guide wires.
      Filters included 23 Greenfield filters, 14 VenaTech filters, and one TrapEase
      filter. In 18 cases of filter/wire entrapment, there was migration of the filter
      to the heart and other central venous structures. Retrieval of the migrated
      filter was successful in only four of the 18 cases, and all of these cases were
      complicated by strut fracture and distant embolization of fragments. One patient
      required resuscitation during retrieval. Successful disengagement was possible in
      20 cases without filter migration. CONCLUSIONS: Iatrogenic migration of an IVC
      filter is an uncommon complication related to wire/filter entrapment. This
      complication can be prevented with knowledge of the patient's history, use of
      proper techniques when placing a central venous catheter, identification of wire
      entrapment at an early stage, and use of an appropriate technique to disengage an
      entrapped wire.

PMID- 24080134
TI  - Presentation, treatment, and outcome differences between men and women undergoing
      revascularization or amputation for lower extremity peripheral arterial disease.
AB  - OBJECTIVE: Prior studies have suggested treatment and outcome disparities between
      men and women for lower extremity peripheral arterial disease after surgical
      bypass. Given the recent shift toward endovascular therapy, which has
      increasingly been used to treat claudication, we sought to analyze sex
      disparities in presentation, revascularization, amputation, and inpatient
      mortality. METHODS: We identified individuals with intermittent claudication and
      critical limb ischemia (CLI) using International Classification of Diseases,
      Ninth Revision codes in the Nationwide Inpatient Sample from 1998 to 2009. We
      compared presentation at time of intervention (intermittent claudication vs CLI),
      procedure (open surgery vs percutaneous transluminal angioplasty or stenting vs
      major amputation), and in-hospital mortality for men and women. Regional and
      ambulatory trends were evaluated by performing a separate analysis of the State
      Inpatient and Ambulatory Surgery Databases from four geographically diverse
      states: California, Florida, Maryland, and New Jersey. RESULTS: From the
      Nationwide Inpatient Sample, we identified 1,797,885 patients (56% male) with
      intermittent claudication (26%) and CLI (74%), who underwent 1,865,999 procedures
      (41% open surgery, 20% percutaneous transluminal angioplasty or stenting, and 24%
      amputation). Women were older at the time of intervention by 3.5 years on average
      and more likely to present with CLI (75.9% vs 72.3%; odds ratio [OR], 1.21; 95%
      confidence interval [CI], 1.21-1.23; P < .01). Women were more likely to undergo
      endovascular procedures for both intermittent claudication (47% vs 41%; OR, 1.27;
      95% CI, 1.25-1.28; P < .01) and CLI (21% vs 19%; OR, 1.14; 95% CI, 1.13-1.15; P <
      .01). From 1998 to 2009, major amputations declined from 18 to 11 per 100,000 in
      men and 16 to 7 per 100,000 in women, predating an increase in total CLI
      revascularization procedures that was seen starting in 2005 for both men and
      women. In-hospital mortality was higher in women regardless of disease severity
      or procedure performed even after adjusting for age and baseline comorbidities
      (.5% vs .2% after percutaneous transluminal angioplasty or stenting for
      intermittent claudication; 1.0% vs .7% after open surgery for intermittent
      claudication; 2.3% vs 1.6% after percutaneous transluminal angioplasty or
      stenting for CLI; 2.7% vs 2.2% after open surgery for CLI; P < .01 for all
      comparisons). CONCLUSIONS: There appears to be a preference to perform
      endovascular over surgical revascularization among women, who are older and have
      more advanced disease at presentation. Percutaneous transluminal angioplasty or
      stenting continues to be popular and is increasingly being performed in the
      outpatient setting. Amputation and in-hospital mortality rates have been
      declining, and women now have lower amputation but higher mortality rates than
      men. Recent improvements in outcomes are likely the result of a combination of
      improved medical management and risk factor reduction.

PMID- 24080135
TI  - Fenestrated endografting of juxtarenal aneurysms after open aortic surgery.
AB  - INTRODUCTION: Juxtarenal aneurysms after previous surgical aortic reconstruction
      constitute a complex clinical scenario. Open redo surgery is technically
      demanding and usually requires suprarenal or supraceliac clamping. Standard
      endovascular repair is prohibited due to the lack of a proximal landing zone. We
      present our experience with fenestrated endovascular aneurysm repair (F-EVAR) in
      the treatment of juxtarenal aneurysms after previous open surgery. METHODS: A
      prospectively maintained database including all patients with juxtarenal
      abdominal aortic aneurysm after previous surgical reconstruction that underwent F
      EVAR within the period from November 2003 to February 2013 under the instruction
      of the senior author. Evaluated outcomes included initial technical success and
      operative mortality and morbidity as well as late survival, target vessel
      patency, aneurysm diameter regression, renal function, and reintervention.
      RESULTS: A total of 35 patients (33 male; mean age, 71.5 +/- 6.2 years) were
      treated. Median interval from the primary surgical reconstruction was 126 months
      (range, 48-223 months). All patients had proximal anatomies precluding standard
      endovascular techniques and were considered high risk for open repair due to
      their comorbidities and redo nature of the operation. In total, 111 vessels were
      targeted: 77 with small fenestrations, 33 with scallops, and 1 vessel with a
      downward branch. The operation was completed by totally endovascular means in 34
      patients (97.1%). In one patient, a retroperitoneal approach was needed to gain
      retrograde access to a renal artery. Operative target vessel perfusion success
      rate was 100%. Operative mortality was 0% and median hospital stay 6 days (range,
      2-40 days). Mean follow-up (FU) was 37.5 +/- 25 months. Mean aneurysm maximal
      diameter decreased from 60 +/- 4 mm to 47 +/- 8 mm (P < .05). No type I endoleak
      was diagnosed, and no reintervention was required during FU. There were eight
      late deaths, all unrelated to the aneurysm. Estimated survival rates at 1, 2, and
      4 years were 92.0% +/- 5.5%, 82.8% +/- 7.9% and 76.9% +/- 9.3%, respectively.
      Three target vessel occlusions occurred during FU. One patient suffered a
      bilateral renal artery occlusion resulting in dialysis. In a second patient, one
      renal artery occluded without clinical symptoms. No other cases of renal function
      deterioration were observed. CONCLUSIONS: F-EVAR is a valid treatment option for
      juxtarenal aneurysms after previous surgical reconstruction. F-EVAR represents a
      less morbid alternative to redo open surgery, has a high technical success rate,
      and shows durability in mid-term FU.

PMID- 24080136
TI  - Visceral stent patency in fenestrated stent grafting for abdominal aortic
      aneurysm repair.
AB  - OBJECTIVE: Fenestrated endovascular abdominal aortic aneurysm repair (F-EVAR) has
      been introduced for treatment of aneurysms in which visceral arteries are
      incorporated. Patency of target vessels has been reported to be excellent.
      Results of the use of stent grafts to accommodate visceral arteries in F-EVAR are
      presented in this study, including an overview of factors that affect outcome.
      METHODS: All patients treated with fenestrated stent grafts in a single center
      between November 2001 and October 2011 were reviewed. Patients treated for
      suprarenal, juxtarenal, and infrarenal short-necked aortic aneurysms were
      included. Patients with thoraco-abdominal aneurysms or aneurysms treated with
      grafts with fixed side branches were excluded. Polytetrafluoroethylene covered
      stents were used routinely since June 2005. Target vessels and stents were
      examined using computed tomography angiography reconstructions. Primary end
      points were primary patency, defined as the absence of occlusion, and loss of
      renal function. Secondary end points were technical success, stenosis (defined as
      a >=50% angiographic diameter reduction), stent fracture, and mortality. RESULTS:
      A total of 138 patients with a median age of 73 years (range, 50-91 years) met
      the inclusion criteria. Median computed tomography angiography follow-up was 13
      months (range, 1-97 months). In total, 392 target vessels were provided with 140
      scallops and 252 fenestrations. Visceral stents (-grafts) were placed in 254
      target vessels. Technical success was obtained in 249 arteries (98.0%). Overall
      stent patency of target vessels was 95.7% at 1 year and 88.6% at 4 years. Renal
      artery stent patency was 97.4% at 1 year and 91.2% at 4 years (96.8% and 89.1%
      for uncovered stents; 97.3% and 92.4% for covered stents, respectively). There
      was no significant difference in patency between covered and uncovered stents in
      renal arteries (P = .71). Renal artery stenosis occurred in 26 stented arteries
      (11.3%) and occlusion in seven arteries. Renal artery stent stenosis occurred
      significantly more in uncovered than in covered stents (P = .04). Stent fractures
      occurred more in uncovered than in covered stents (P = .01) and was associated
      with a significantly lower visceral stent patency rate (P < .01). During follow
      up, 13 patients developed permanent renal function impairment (9.4%), of which
      two required permanent dialysis (1.4%). Renal dysfunction was significantly
      associated with renal stent occlusion or stenosis (P < .01). CONCLUSIONS: Patency
      rates of visceral artery stent (-grafts) in F-EVAR were 95.7% at 1 year and 88.6%
      at 4 years. Patency rates were affected by stent fractures, which occurred more
      in uncovered compared with covered stents. Renal artery stent stenosis occurred
      more in uncovered compared with covered stents. Renal dysfunction was
      significantly associated with renal stent occlusion or stenosis.

PMID- 24080137
TI  - Chinese My Trauma Recovery, a Web-based intervention for traumatized persons in
      two parallel samples: randomized controlled trial.
AB  - BACKGROUND: Guided self-help interventions for PTSD (post-traumatic stress
      disorder) are a promising tool for the dissemination of contemporary
      psychological treatment. OBJECTIVE: This study investigated the efficacy of the
      Chinese version of the My Trauma Recovery (CMTR) website. METHODS: In an urban
      context, 90 survivors of different trauma types were recruited via Internet
      advertisements and allocated to a randomized controlled trial (RCT) with a
      waiting list control condition. In addition, in a rural context, 93 survivors
      mainly of the 2008 Sichuan earthquake were recruited in-person for a parallel RCT
      in which the website intervention was conducted in a counseling center and guided
      by volunteers. Assessment was completed online on a professional Chinese survey
      website. The primary outcome measure was the Post-traumatic Diagnostic Scale
      (PDS); secondary outcome measures were Symptom Checklist 90-Depression (SCL-D),
      Trauma Coping Self-Efficacy Scale (CSE), Post-traumatic Cognitive Changes (PCC),
      and Social Functioning Impairment (SFI) questionnaires adopted from the My Trauma
      Recovery website. RESULTS: For the urban sample, findings indicated a significant
      group*time interaction in post-traumatic symptom severity (F1,88=7.65, P=.007).
      CMTR reduced post-traumatic symptoms significantly with high effect size after
      one month of treatment (F1,45=15.13, Cohen's d=0.81, P<.001) and the reduction
      was sustained over a 3-month follow-up (F1,45=17.29, Cohen's d=0.87, P<.001). In
      the rural sample, the group*time interaction was also significant in post
      traumatic symptom severity (F1,91=5.35, P=.02). Post-traumatic symptoms decreased
      significantly after treatment (F1,48=43.97, Cohen's d=1.34, P<.001) and during
      the follow-up period (F1,48=24.22, Cohen's d=0.99, P<.001). Additional outcome
      measures (post-traumatic cognitive changes, depression) indicated a range of
      positive effects, in particular in the urban sample (group*time interactions:
      F1,88=5.32-8.37, all Ps<.03), contributing to the positive evidence for self-help
      interventions. Differences in the effects in the two RCTs are exploratorily
      explained by sociodemographic, motivational, and setting feature differences
      between the two samples. CONCLUSIONS: These findings give support for the short
      term efficacy of CMTR in the two Chinese populations and contribute to the
      literature that self-help Web-based programs can be used to provide mental health
      help for traumatized persons. TRIAL REGISTRATION: Australia New Zealand Clinical
      Trials Registry (ANZCTR): ACTRN12611000951954;
      https://www.anzctr.org.au/Trial/Registration/TrialReview.aspx?ACTRN=1261100095195
      (Archived by WebCite at http://www.webcitation.org/6G7WyNODk).

PMID- 24080138
TI  - Effect of Emdogain enamel matrix derivative and BMP-2 on the gene expression and
      mineralized nodule formation of alveolar bone proper-derived stem/progenitor
      cells.
AB  - The objective of this study was to evaluate the effect of Emdogain (Enamel Matrix
      Derivative, EMD) and Bone Morphogenetic Protein-2 (BMP-2), either solely or in
      combination, on the gene expression and mineralized nodule formation of alveolar
      bone proper-derived stem/progenitor cells. Stem/progenitor cells were isolated
      from human alveolar bone proper, magnetically sorted using STRO-1 antibodies,
      characterized flowcytometrically for their surface markers' expression, and
      examined for colony formation and multilineage differentiation potential.
      Subsequently, cells were treated over three weeks with 100 MUg/ml Emdogain (EMD
      Group), or 100 ng/ml BMP-2 (BMP-Group), or a combination of 100 ng/ml BMP-2 and
      100 MUg/ml Emdogain (BMP/EMD-Group). Unstimulated stem/progenitor cells (MACS(+)
      Group) and osteoblasts (OB-Group) served as controls. Osteogenic gene expression
      was analyzed using RTq-PCR after 1, 2 and 3 weeks (N = 3/group). Mineralized
      nodule formation was evaluated by Alizarin-Red staining. BMP and EMD up-regulated
      the osteogenic gene expression. The BMP Group showed significantly higher
      expression of Collagen-I, III, and V, Alkaline phosphatase and Osteonectin
      compared to MACS(+)- and OB-Group (p < 0.05; Two-way ANOVA/Bonferroni) with no
      mineralized nodule formation. Under in-vitro conditions, Emdogain and BMP-2 up
      regulate the osteogenic gene expression of stem/progenitor cells. The combination
      of BMP-2 and Emdogain showed no additive effect and would not be recommended for
      a combined clinical stimulation. 

PMID- 24080139
TI  - Head posture and pharyngeal airway volume changes after bimaxillary surgery for
      mandibular prognathism.
AB  - PURPOSE: The purpose of this study was to evaluate head posture and the
      pharyngeal airway volume changes using 3D imaging after bimaxillary surgery in
      mandibular prognathism patients by null hypothesis. MATERIALS AND METHODS: Cone
      beam computed tomography (CBCT) scans were obtained for 25 mandibular prognathism
      patients before bimaxillary surgery (T1) and 6 months after surgery (T2). The
      head posture of each patient was assessed by measuring cranio-cervical angle on a
      midsagittal plane passing through the anterior nasal spine at T1 and T2.
      Additionally, the volume of each subject's pharyngeal airway was measured using
      InVivoDental 3D imaging software. RESULTS: The cranio-cervical angle increased
      significantly 6 months after bimaxillary surgery (p < 0.01). The total volume of
      the pharyngeal airway slightly decreased (p > 0.05) at the same timepoints, while
      naso- and oro-pharyngeal airway volume decreased significantly (p < 0.05, p <
      0.05). There was significant relationship between the changes of head posture and
      those of total airway volume (p < 0.05). CONCLUSION: The null hypothesis was
      rejected. Bimaxillary surgery resulted in significant head flexion and a slight
      decrease in total pharyngeal airway volume.

PMID- 24080140
TI  - Treatment outcomes of sinonasal adenoid cystic carcinoma: 30 cases from a single
      institution.
AB  - OBJECTIVE: To establish the clinical features and prognostic factors of sinonasal
      adenoid cystic carcinoma (ACC). MATERIAL AND METHODS: Thirty patients with
      histopathological diagnosis of sinonasal ACC who were treated at Severance
      Hospital between 1990 and 2010 were included in this retrospective chart review
      study. RESULTS: The 5-year disease-specific survival and disease-free survival
      rates were 75.3% and 37.2%, respectively. The maxillary sinus (63.3%) and nasal
      cavity (23.3%) were the most common sites of primary tumour. Most patients were
      diagnosed with advanced-stage (III/IV) disease (80.0%) and had undergone surgery
      and postoperative radiotherapy (70.0%). The most common histopathological subtype
      was cribriform type (40.9%). Local recurrence rate and distant metastasis rates
      were 26.7% and 23.3%, respectively. The mean time from primary treatment to
      recurrence was 44.5 months. Sinonasal ACC patients with stage IV and T4 disease
      had significantly worse survival than those with low stage and T disease.
      Patients with local recurrence had worse disease-specific survival than those
      with distant recurrence. Distant metastasis was associated with disease-free
      survival but not disease-specific survival. CONCLUSION: Despite the frequent
      occurrence of distant metastasis, early diagnosis and effective local control
      seemed to be the most important factors influencing the survival of sinonasal
      ACC.

PMID- 24080141
TI  - Outcome of laparoscopy-guided hysteroscopic tubal catheterization for infertility
      due to proximal tubal obstruction.
AB  - STUDY OBJECTIVE: To determine pregnancy outcomes after laparoscopy-guided
      hysteroscopic tubal catheterization and to report its role in the era of in vitro
      fertilization. DESIGN: Clinical cases series (Canadian Task Force classification
      II-3). SETTING: Reproductive surgery center. PATIENTS: Patients with unilateral
      or bilateral proximal tubal obstruction as the only cause of infertility were
      included. INTERVENTIONS: Laparoscopy-guided hysteroscopic tubal catheterization.
      MEASUREMENTS AND MAIN RESULTS: Only the first spontaneous conception was
      considered. Cumulative conception rate (CCR) was calculated using Kaplan-Meier
      survival analysis. Of 168 women included, 107 (63.7%) had bilateral proximal
      obstruction and 61 (36.3%) had unilateral obstruction. The successful
      recanalization rate was 54.2% per tube and 61.9% per patient. In the 93 patients
      in whom at least 1 fallopian tube was successfully recanalized, 40 spontaneous
      pregnancies (43.0%) occurred within 24 months, of which 35 (37.6%) were
      intrauterine pregnancies and 28 (30.1%) resulted in live births. The CCR was
      37.6% at 1 year and 43.7% at 2 years. Patients with unilateral obstruction in
      whom cannulation was successful had the highest CCR (60.7% at 2 years).
      CONCLUSION: Successful tubal cannulation led to significant improvement in the
      pregnancy rate, which suggests that women with a proximal tubal block could be
      considered for laparoscopy-guided hysteroscopic cannulation, which is still a
      viable alternative to in vitro fertilization.

PMID- 24080142
TI  - Mutations in the mitochondrial gene C12ORF65 lead to syndromic autosomal
      recessive intellectual disability and show genotype phenotype correlation.
AB  - Homozygosity mapping and exome sequencing in two affected siblings of a
      consanguineous family with mild intellectual disability, spastic paraplegia, and
      strabismus revealed a homozygous premature stop mutation at codon 139 of
      C12ORF65. Two previous studies reported truncating mutations at positions 84 and
      132 of the protein. However, symptoms of the referred patients were only
      partially overlapping. Considering our findings, we now conclude that truncating
      mutations in C12ORF65 lead to a variable phenotype with intellectual disability,
      spastic paraplegia, and ophthalmoplegia as common symptoms. Further, we confirm a
      genotype-phenotype correlation between increasing length of the truncated protein
      and decreasing severity of symptoms. 

PMID- 24080143
TI  - The impact of combined use of fall-risk medications and antithrombotics on injury
      severity and intracranial hemorrhage among older trauma patients.
AB  - PURPOSE: Use of fall-risk medications (medications that increase risk of falling
      in the elderly as defined by Beers criteria, STOPP/START criteria, and other
      literature) or antithrombotics is common in the elderly, and the impact of their
      concomitant use should be assessed in regards to fall injuries. The primary
      objective of this study is to assess the simultaneous outpatient use of fall-risk
      medications and antithrombotics in elderly fall-patients, and secondarily to
      analyze the injury severity score and occurrence of intracranial hemorrhage.
      METHODS: Consecutive chart review at a level 2 trauma center in California, USA
      from August 01, 2009 to October 31, 2010. Records included 112 patients at least
      65 years of age admitted with an outpatient fall. Fisher's exact and Student's t
      tests were used (alpha 0.05, two-tailed) to examine prescribing patterns,
      intracranial hemorrhage occurrence, and injury severity score. Regression
      adjusted for antithrombotic and fall-risk medication type and number, opiate use,
      co-morbidities, age, and gender. RESULTS: Thirty-nine percent (44/112) of
      outpatients were prescribed antithrombotics plus fall-risk medications. The mean
      injury severity score (ISS) was 13.3 (range 1-26, standard deviation 7.2) for
      patients taking both medication classes versus 9.7 (range 1-25, standard
      deviation 7.5) for patients taking antithrombotics alone (p = 0.027).
      Additionally, in patients over 80 years of age, intracranial hemorrhage occurred
      more frequently with the use of antithrombotics plus fall-risk medications versus
      antithrombotics alone (18/29 = 62.1% versus 7/24 = 29.2%, p = 0.027, odds ratio =
      3.974, 95% confidence interval = 1.094-15.010). Multivariate analyses showed an
      independent relationship between intracranial hemorrhage occurrence and type of
      therapy, as well as injury severity score and simultaneous therapy with fall-risk
      medications and antithrombotics. CONCLUSION: Simultaneous prescribing of
      antithrombotics and fall-risk medications is common. For outpatients over 80
      years of age, the odds of experiencing a post-fall intracranial hemorrhage are 4
      times higher when prescribed antithrombotics plus fall-risk medications compared
      to antithrombotics alone, and injury severity is higher with combined use of
      these medication classes.

PMID- 24080145
TI  - Hybrid MnO2 film with agarose gel for enhancing the structural integrity of thin
      film supercapacitor electrodes.
AB  - We report on the fabrication of a robust hybrid film containing MnO2 for
      achieving large areal capacitances. An agarose gel, as an ion-permeable and
      elastic layer coated on a current collector, plays a key role in stabilizing the
      deposited pseudocapacitive MnO2. Cyclic voltammetry and electrochemical impedance
      spectroscopy data indicate that the hybrid electrode is capable of exhibiting a
      high areal capacitance up to 52.55 mF cm(-2), with its superior structural
      integrity and adhesiveness to the current collector being maintained, even at a
      high MnO2 loading. 

PMID- 24080144
TI  - Role of selenium and glutathione peroxidase on development, growth, and oxidative
      balance in rat offspring.
AB  - Selenium (Se), an essential trace metal, is important in both growth and
      reproduction and is the constituent of different selenoproteins. The glutathione
      peroxidase (GPx) family is the most studied as it prevents oxidative stress.
      Liver oxidation is considered as another mechanism involved in low birth weight.
      Therefore, in order to ascertain whether GPx is related to the effects of Se on
      growth during gestation and lactation, three groups of rat pups were used:
      control, Se deficient (SD), and Se supplemented (SS). Morphological parameters
      and reproductive indices were evaluated. Hepatic Se levels were measured by
      graphite furnace atomic absorption while spectrophotometry was used for activity
      of antioxidant enzymes and oxidative stress markers in liver and western blotting
      for expression of hepatic GPx1 and GPx4. The SD diet increased mortality at
      birth; decreased viability and survival indices; and stunted growth, length, and
      liver development in offspring, thus decreasing hepatic Se levels, GPx,
      glutathione reductase, and catalase activities, while increasing superoxide
      dismutase activity and protein oxidation. The SS diet counteracted all the above
      results. GPx1 expression was heavily regulated by Se dietary intake; however,
      although Se dietary deficiency reduced GPx4 expression, this decrease was not as
      pronounced. Therefore, it can be concluded that Se dietary intake is intimately
      related to growth, length, and directly regulating GPx activity primarily via
      GPx1 and secondly to GPx4, thus affecting liver oxidation and development. These
      results suggest that if risk of uterine growth retardation is suspected, or if a
      neonate with low birth weight presents with signs of liver oxidation, it may be
      beneficial to know about Se status. 

PMID- 24080146
TI  - A unique mouse model for investigating the properties of amyotrophic lateral
      sclerosis-associated protein TDP-43, by in utero electroporation.
AB  - TDP-43 is a discriminative protein that is found as intracellular aggregations in
      the neurons of the cerebral cortex and spinal cord of patients with amyotrophic
      lateral sclerosis (ALS); however, the mechanisms of neuron loss and its relation
      to the aggregations are still unclear. In this study, we generated a useful model
      to produce TDP-43 aggregations in the motor cortex using in utero electroporation
      on mouse embryos. The plasmids used were full-length TDP-43 and C-terminal
      fragments of TDP-43 (wild-type or M337V mutant) tagged with GFP. For the full
      length TDP-43, both wild-type and mutant, electroporated TDP-43 localized mostly
      in the nucleus, and though aggregations were detected in embryonic brains, they
      were very rarely observed at P7 and P21. In contrast, TDP-43 aggregations were
      generated in the brains electroporated with the C-terminal TDP-43 fragments as
      previously reported in in vitro experiments. TDP-43 protein was distributed
      diffusely-not only in the nucleus, but also in the cytoplasm-and the inclusion
      bodies were ubiquitinated and included phosphorylated TDP-43, which reflects the
      human pathology of ALS. This model using in utero electroporation of pathogenic
      genes into the brain of the mouse will likely become a useful model for studying
      ALS and also for evaluation of agents for therapeutic purpose, and may be
      applicable to other neurodegenerative diseases, as well. 

PMID- 24080147
TI  - Effects of rehabilitative training on recovery of hand motor function: a review
      of animal studies.
AB  - Neuromotor systems have the capacity for functional recovery following damage to
      the central nervous system. This recovery can be enhanced by rehabilitative
      training. Animal studies in which artificial damage is induced in a specific
      region of the brain or spinal cord of rodents or monkeys have contributed to our
      understanding of the effects of rehabilitative training. In this article, I
      provide an overview of recent studies in which experimental animals were used to
      investigate the effects of rehabilitative training on motor recovery and brain
      plasticity. A study from my group in the macaque monkey reported the effects of
      hand motor training on motor recovery after lesioning of the primary motor cortex
      (M1) or the corticospinal tract at the cervical level. In monkeys that had
      undergone extensive post-lesion training, manual dexterity recovered to previous
      levels. Rehabilitative training was more effective in promoting recovery of
      manual dexterity when initiated immediately after the corticospinal tract lesion
      rather than 1 month later. Both functional brain imaging and gene expression
      analyses suggest that functional and structural changes may occur in undamaged
      motor areas during recovery of hand function after M1 or corticospinal tract
      lesions. 

PMID- 24080148
TI  - Pooled platelet product using the Acrodose plus system: evaluation of
      feasibility, safety and efficacy.
AB  - BACKGROUND: Pooling of whole blood-derived platelets is not practiced in India.
      Currently available data shows that pooled platelets are equivalent in quality
      and less costly when compared with apheresis platelets. AIM: To evaluate
      feasibility, safety and efficacy of pooled platelets using the Acrodose Plus
      system. MATERIAL AND METHODS: Standardization of platelet pooling procedure was
      done. Sterile docking device was used to maintain closed system. Pools of ABO
      compatible platelets (N=40) as well as ABO incompatible (N=10) pooled platelets
      were studied. ABO antibody titers were studied before and after pooling in case
      of ABO incompatible platelet pools. Corrected count increments (CCIs) (at 1h and
      24h) were noted after transfusion of pooled platelets and Apheresis platelets in
      matched patient groups. RESULTS: Loss of platelet product due to pooling and
      leucodepletion was not statistically significant (p=0.23). Leucodepletion >3 log
      was achieved in all pooled platelets. The total platelet content, time taken for
      procedure and pH were within acceptable limits. There were no issues related to
      platelet availability and turn around time during the study period. There was a
      reduction in the ABO antibody titers after pooling in case of the ABO
      incompatible pools. None of the pooled platelets showed evidence of bacterial
      contamination on testing with eBDS system at 18 h and 24h intervals after
      pooling. CCI with pooled platelets was equivalent to that with apheresis
      platelets at 1h (p=0.36) and 24h (p=0.15). CONCLUSION: Whole blood derived
      platelets can be pooled safely using closed system without altering the platelet
      quality in vitro as well as in vivo survival post transfusion. Pooled platelets
      can be a cost effective and safe alternative to thrombocytopenic patients whose
      transfusion requirements cannot be fulfilled with apheresis platelets alone.

PMID- 24080149
TI  - Paraoxonase-1 activity affects the clopidogrel response in CYP2C19 loss-of
      function carriers.
AB  - BACKGROUND: The impact of paraoxonase-1 (PON1) activity on the response to
      clopidogrel may differ in patients treated with drug-eluting stents (DES) in
      association with CYP2C19 loss-of-function (LOF) polymorphisms. METHODS: This
      study included 112 Japanese patients receiving clopidogrel (75 mg/day) and
      aspirin (100mg/day) who underwent optical coherence tomography (OCT) examination
      9 months after DES implantation. The CYP2C19 genotype was analyzed and LOF
      carriers (1/2, 1/3, 2/2, 3/3, 2/3) were identified. At the 9-month follow-up,
      platelet reactivity was determined by measuring the P2Y12 reactivity unit (PRU)
      using a VerifyNow P2Y12 assay, PON1 activity was evaluated and intra-stent
      thrombus was evaluated by OCT. RESULTS: Of the 112 Japanese patients, 75 were LOF
      carriers (67.0%). The patients were divided into tertiles according to the PON1
      activity (tertile 1; <230 U/L, tertile 2; 230-283U/L, tertile 3; >283 U/L). In
      the VerifyNowP2Y12 analysis, tertile 1 had a higher PRU than tertiles 2 and 3 in
      LOF carriers, and there was no difference among tertiles in non-carriers. The
      highest incidence of intra-stent thrombus was observed in tertile 1 followed by
      tertiles 2 and 3 in LOF carriers, whereas there was no such difference in non
      carriers. Multivariate analysis revealed that LOF carriers and PON1 activity
      tertile 1 were independent predictors of intra-stent thrombus in all patients. In
      LOF carriers, tertile 1 was the only independent predictor for intra-stent
      thrombus. CONCLUSION: Low PON1 activity is associated with a low response to
      clopidogrel and a high frequency of intra-stent thrombus only in LOF carriers.

PMID- 24080150
TI  - Thromboprophylaxis patterns, risk factors, and outcomes of care in the medically
      ill patient population.
AB  - INTRODUCTION: Medically ill, hospitalized patients are at increased risk for
      venous thromboembolism (VTE) after discharge. This study aimed to examine
      thromboprophylaxis patterns, risk factors, and post-discharge outcomes. METHODS:
      This was a retrospective claims analysis involving administrative claims data and
      in-patient data abstracted from a sample of hospital charts. Patients aged >= 40
      years hospitalized for >= 2 days for nonsurgical reasons between 2005 and 2009
      were included. Hospital chart data were abstracted for a random sample of
      patients without evidence of anticoagulant use at 30 days post-discharge. The
      combined data determined whether in-patient thromboprophylaxis (anticoagulant or
      mechanical prophylaxis) reduces risk of VTE at 90 days post-discharge. Hazard
      ratios (HR) and odds ratios (OR) were calculated using Cox proportional hazard
      models and logistic regression. RESULTS: Of 141,628 patients in the claims
      analysis, 3.9% received anticoagulants (3.6% warfarin). VTE, rehospitalization,
      and mortality rates were 1.9%, 17.2%, and 6.2%, respectively. The strongest
      predictors of post-discharge VTE were history of VTE (HR=4.0, 95% confidence
      interval [CI]: 3.3-4.8), and rehospitalization (HR=3.9, 95% CI: 3.6-4.3). Of 504
      medical charts, 209 (41.5%) reported in-patient thromboprophylaxis. There was no
      statistically significant difference in post-discharge VTE rates between patients
      who did and did not receive in-patient thromboprophylaxis. All-cause mortality
      was greater among patients without use of VTE prophylaxis. CONCLUSION:
      Utilization rates of in-hospital and post-discharge VTE prophylaxis were low. In
      hospital VTE prophylaxis did not reduce the risk of post-discharge VTE in the
      absence of post-discharge anticoagulation. Combined in-patient and post-discharge
      thromboprophylaxis lowered the odds of short-term, all-cause post-discharge
      mortality.

PMID- 24080151
TI  - Life after death: the Gorilla Family of the Senckenberg Museum (Frankfurt/Main).
AB  - This essay examines the history of the gorilla family placed on display at the
      Senckenberg Museum in Frankfurt am Main, Germany in 1907. It considers, first,
      how it came to be; second, what it signified both at the time--the museal
      domestication of an ape previously considered to be a terrifying foe and a
      monstrous possible ancestor--and third, what it meant ninety years later, when I
      sought out its history and found more than I bargained for.

PMID- 24080152
TI  - Cutaneous allodynia as a predictor of migraine chronification.
AB  - Cutaneous allodynia is a common feature accompanying migraine attacks and
      considered a clinical marker for central sensitization. In a longitudinal study,
      we wanted to investigate if allodynia in migraine patients is a predictor of
      increasing frequency of migraine days. We included 3029 well-defined, web-based
      migraine patients (86% female, mean age 42.8 +/- 11.4 years, 61% migraine without
      aura). Questionnaires on migraine characteristics (including allodynia),
      depression and demographic factors were applied. The number of migraine days was
      measured twice. Multivariate regression models were used, with correction for
      other factors that are involved in the relation between allodynia and the number
      of migraine attacks or migraine days, with specific focus on depression. Of all
      2331 eligible migraine patients, 1624 (70%) had allodynia. Lifetime depression
      was an independent risk factor for allodynia (odds ratio 1.52, 95% confidence
      interval 1.26-1.84), as well as female gender, low age at onset, and high
      migraine attack frequency. Analysis of the longitudinal data (in migraineurs with
      a follow-up period of >6 months) showed that, apart from the known risk factors
      (low age at onset, high baseline number of migraine days, and depression),
      allodynia was an independent predictor for increase in number of migraine days
      over a mean follow-up period of 93 +/- 30 weeks (median 103 weeks, range 26-160
      weeks). Cutaneous allodynia is a risk factor for migraine chronification and may
      warrant preventive treatment strategies. 

PMID- 24080153
TI  - Undirected compensatory plasticity contributes to neuronal dysfunction after
      severe spinal cord injury.
AB  - Severe spinal cord injury in humans leads to a progressive neuronal dysfunction
      in the chronic stage of the injury. This dysfunction is characterized by
      premature exhaustion of muscle activity during assisted locomotion, which is
      associated with the emergence of abnormal reflex responses. Here, we hypothesize
      that undirected compensatory plasticity within neural systems caudal to a severe
      spinal cord injury contributes to the development of neuronal dysfunction in the
      chronic stage of the injury. We evaluated alterations in functional,
      electrophysiological and neuromorphological properties of lumbosacral circuitries
      in adult rats with a staggered thoracic hemisection injury. In the chronic stage
      of the injury, rats exhibited significant neuronal dysfunction, which was
      characterized by co-activation of antagonistic muscles, exhaustion of locomotor
      muscle activity, and deterioration of electrochemically-enabled gait patterns. As
      observed in humans, neuronal dysfunction was associated with the emergence of
      abnormal, long-latency reflex responses in leg muscles. Analyses of circuit,
      fibre and synapse density in segments caudal to the spinal cord injury revealed
      an extensive, lamina-specific remodelling of neuronal networks in response to the
      interruption of supraspinal input. These plastic changes restored a near-normal
      level of synaptic input within denervated spinal segments in the chronic stage of
      injury. Syndromic analysis uncovered significant correlations between the
      development of neuronal dysfunction, emergence of abnormal reflexes, and
      anatomical remodelling of lumbosacral circuitries. Together, these results
      suggest that spinal neurons deprived of supraspinal input strive to re-establish
      their synaptic environment. However, this undirected compensatory plasticity
      forms aberrant neuronal circuits, which may engage inappropriate combinations of
      sensorimotor networks during gait execution. 

PMID- 24080154
TI  - HER2 testing: current status and future directions.
AB  - Accurate determination of human epidermal growth factor receptor 2 (HER2) status
      is critical for optimizing breast cancer outcomes. In 2007, the American Society
      of Clinical Oncology (ASCO) and the College of American Pathologists (CAP)
      developed guidelines for HER2 testing to reduce inaccuracy. However, current
      ASCO/CAP criteria may restrict access to HER2-targeted therapy for some patient
      groups who would derive a clear clinical benefit. ASCO/CAP are currently
      reviewing their guidelines to further optimize HER2 testing and include emerging
      techniques. Guidelines are critical for optimizing care, as is ongoing research
      into techniques that accurately and reproducibly assess HER2 status.

PMID- 24080155
TI  - Human papilloma virus positive oropharyngeal squamous cell carcinoma: a growing
      epidemic.
AB  - The incidence of oropharyngeal squamous cell carcinoma (OPSCC) is increasing
      despite a decrease in tobacco use. Almost 20-30% of patients with OPSCC do not
      have the traditional risk factors of smoking and alcohol use and in a vast
      majority of these patients, the human papilloma virus (HPV) appears to drive the
      malignant transformation. HPV induced malignant transformation is attributed to
      two viral oncogenes and their non-structural protein products (E6 and E7). These
      two proteins appear to affect carcinogenesis by their inhibitory effects on p53
      and retinoblastoma proteins (Rb). Patients with HPV mediated OPSCC seem to have a
      better prognosis compared to their non-HPV counterparts. However, in the absence
      of strong evidence, standard of care at this time for OPSCC does not differ based
      on HPV status. Current research is focused on the role of de-escalation of
      treatment and elucidation of prognostic markers in this unique population. This
      review focuses on the pathogenesis of HPV mediated OPSCC and details the current
      evidence in the management of these patients.

PMID- 24080157
TI  - Distribution, diversity and density of wolbachial infections in cladocerans and
      copepods from Thailand.
AB  - Species of the genus Wolbachia comprise a group of Rickettsia-like, maternally
      inherited bacteria that cause several reproductive alterations in arthropod
      hosts. The best known are cytoplasmic incompatibility and feminization. Here, the
      first systematic surveys of wolbachial infections in cladocerans and copepods
      from six geographic regions of Thailand, including Northern, Northeastern,
      Western, Central, Eastern and Southern are reported. Using gene amplification
      assays with wsp and groE primers, wolbachiae were detected in 239 (4 spp.) of
      1885 (57 spp.) copepods and cladocerans from all regions of Thailand surveyed.
      Screening results obtained with wsp primers or groE primers were similar in all
      cases. The presence of wolbachiae was only detected in copepods, not in
      cladocerans. Sex ratio analyses of the progeny of two species of copepods,
      Mesocyclops aspericornis and Mesocyclops thermocyclopoides, naturally or
      artificially infected with wolbachiae showed infection causes feminization
      (female-bias). The relative density if infection in naturally infected
      populations of three copepod species, M. thermocyclopoides, Heliodiaptomus
      elegans and Neodiaptomus blachei, were determined using real-time quantitative
      PCR assay based on the wsp gene. The density of wolbachiae in M.
      thermocyclopoides was significantly higher than in the other two species. These
      results suggest that wolbachial infections are distributed throughout Thailand,
      and that possibly the natural occurrence of these in copepods may be due to their
      predation on mosquito larvae. This apparent novel biology may have importance as
      a genetic drive system for control of vector borne diseases in the future. 

PMID- 24080156
TI  - A systematic review of dual targeting in HER2-positive breast cancer.
AB  - BACKGROUND: Human epidermal growth factor receptor 2 (HER2) is overexpresed in 15
      20% of all breast cancers. Treatment with trastuzumab has led to an improved
      outcome and prolonged survival of HER2-positive breast cancer patients and today
      the drug is established as standard of care in both the adjuvant and metastatic
      settings. However, trastuzumab resistance is common and a major focus in the
      treatment of HER2-positive breast cancer has been developing therapeutic agents
      to either potentiate the effect of trastuzumab or to target cells which have
      become resistant to trastuzumab. The present review addresses efficacy and
      toxicity of dual targeting in HER2-positive breast cancer. MATERIALS AND METHODS:
      A computer-based literature search was carried out using PubMed; data reported at
      international meetings and clinicaltrials.gov was included. RESULTS: This paper
      describes efficacy and safety of lapatinib, pertuzumab or trastuzumab-DM1 in
      combination with trastuzumab in the (neo)adjuvant and metastatic settings.
      Furthermore, combinations of trastuzumab and drugs targeting the downstream
      pathway are described. CONCLUSION: Dual blockade is likely to represent a
      substantial advance for patients with HER2-positive breast cancer. However, the
      relevant subpopulation remains to be defined and side effects including
      cardiotoxicity might be a limiting factor to the use. There is an urgent need for
      prospective biomarker-driven trials to identify patients for whom dual targeting
      is cost-effective.

PMID- 24080159
TI  - Activation of AMPK protects against hydrogen peroxide-induced osteoblast
      apoptosis through autophagy induction and NADPH maintenance: new implications for
      osteonecrosis treatment?
AB  - Elevated hydrogen peroxide (H2O2) causes osteoblast dysfunction and apoptosis,
      serving as an important contributor to the development of osteonecrosis. Here we
      aimed to understand the role of AMP-activated protein kinase (AMPK) in the
      process. We observed a high level of AMPK activation in surgery isolated
      patients' osteonecrosis tissues. In cultured osteoblastoma MG63 cells, H2O2
      stimulation induced significant AMPK activation, oxidative stress, cell death and
      apoptosis. Inhibition of AMPK by its inhibitor (compound C) or by shRNA-mediated
      knockdown dramatically enhanced H2O2-induced MG63 cell apoptosis, while over
      expression of AMPK in HEK-293 cells alleviated H2O2-induced cell damage. These
      results confirmed that H2O2-activated AMPK is pro-cell survival. We observed that
      H2O2 induced protective autophagy in MG63 cells, and AMPK-dependent Ulk1
      activation and mTORC1 (mTOR complex 1) inactivation might involve autophagy
      activation. Further, AMPK activation inhibited H2O2-induced oxidative stress,
      probably through inhibiting NADPH (nicotinamide adenine dinucleotide phosphate)
      depletion, since more NADPH depletion and oxidative stress were induced by H2O2
      in AMPK deficient MG63 cells. Finally, we observed a significant AMPK activation
      in H2O2-treated primary cultured and transformed (MC3T3-E1) osteoblasts, and AMPK
      inhibitor compound C enhanced death by H2O2 in these cells. Based on these
      results, we concluded that H2O2-induced AMPK activation is pro-survival and anti
      apoptosis in osteoblasts. Autophagy induction and NADPH maintenance are involved
      in AMPK-mediated pro-survival effects. AMPK might represent a novel molecular
      target for osteonecrosis treatment. 

PMID- 24080158
TI  - Secreted Frizzled-related protein potentiation versus inhibition of Wnt3a/beta
      catenin signaling.
AB  - Wnt signaling regulates a variety of cellular processes during embryonic
      development and in the adult. Many of these activities are mediated by the
      Frizzled family of seven-pass transmembrane receptors, which bind Wnts via a
      conserved cysteine-rich domain (CRD). Secreted Frizzled-related proteins (sFRPs)
      contain an amino-terminal, Frizzled-like CRD and a carboxyl-terminal, heparin
      binding netrin-like domain. Previous studies identified sFRPs as soluble Wnt
      antagonists that bind directly to Wnts and prevent their interaction with
      Frizzleds. However, subsequent observations suggested that sFRPs and Frizzleds
      form homodimers and heterodimers via their respective CRDs, and that sFRPs can
      stimulate signal transduction. Here, we present evidence that sFRP1 either
      inhibits or enhances signaling in the Wnt3a/beta-catenin pathway, depending on
      its concentration and the cellular context. Nanomolar concentrations of sFRP1
      increased Wnt3a signaling, while higher concentrations blocked it in HEK293 cells
      expressing a SuperTopFlash reporter. sFRP1 primarily augmented Wnt3a/beta-catenin
      signaling in C57MG cells, but it behaved as an antagonist in L929 fibroblasts.
      sFRP1 enhanced reporter activity in L cells that were engineered to stably
      express Frizzled 5, though not Frizzled 2. This implied that the Frizzled
      expression pattern could determine the response to sFRP1. Similar results were
      obtained with sFRP2 in HEK293, C57MG and L cell reporter assays. CRDsFRP1
      mimicked the potentiating effect of sFRP1 in multiple settings, contradicting
      initial expectations that this domain would inhibit Wnt signaling. Moreover,
      CRDsFRP1 showed little avidity for Wnt3a compared to sFRP1, implying that the
      mechanism for potentiation by CRDsFRP1 probably does not require an interaction
      with Wnt protein. Together, these findings demonstrate that sFRPs can either
      promote or suppress Wnt/beta-catenin signaling, depending on cellular context,
      concentration and most likely the expression pattern of Fzd receptors. 

PMID- 24080160
TI  - Interleukin-1-induced activation of the small GTPase Rac1 depends on receptor
      internalization and regulates gene expression.
AB  - Interleukin 1 (IL-1) triggers the internalization of its cognate receptor from
      the plasma membrane. We recently demonstrated that this internalization is of
      critical importance for the IL-1-induced gene expression. In this study we report
      that the IL-1-induced activation of the small GTPase Rac1 requires receptor
      endocytosis. We further show that the depletion of Rac1 reduces the IL-1
      dependent gene expression without affecting signaling events that are initiated
      at the plasma membrane. Collectively, we provide evidence for a key role of Rac1
      in a pathway that regulates IL-1-induced gene expression depending on receptor
      endocytosis. 

PMID- 24080162
TI  - Two polymorphic variants of ABCC1 selectively alter drug resistance and inhibitor
      sensitivity of the multidrug and organic anion transporter multidrug resistance
      protein 1.
AB  - In this study we compared the in silico predictions of the effect of ABCC1
      nonsynonymous single nucleotide polymorphisms (nsSNPs) with experimental data on
      MRP1 transport function and response to chemotherapeutics and multidrug
      resistance protein 1 (MRP1) inhibitors. Vectors encoding seven ABCC1 nsSNPs were
      stably expressed in human embryonic kidney (HEK) cells, and levels and
      localization of the mutant MRP1 proteins were determined by confocal microscopy
      and immunoblotting. The function of five of the mutant proteins was determined
      using cell-based drug and inhibitor sensitivity and efflux assays, and membrane
      based organic anion transport assays. Predicted consequences of the mutations
      were determined by multiple bioinformatic methods. Mutants C43S and S92F were
      correctly routed to the HEK cell plasma membrane, but the levels were too low to
      permit functional characterization. In contrast, levels and membrane trafficking
      of R633Q, G671V, R723Q, A989T, and C1047S were similar to wild-type MRP1. In cell
      based assays, all five mutants were equally effective at effluxing calcein, but
      only two exhibited reduced resistance to etoposide (C1047S) and vincristine
      (A989T; C1047S). The GSH-dependent inhibitor LY465803 (LY465803 [N-[3-(9-chloro-3
      methyl-4-oxo-4H-isoxazolo-[4,3-c]quinolin-5-yl)-cyclohexylmethyl]-benzamide)] was
      less effective at blocking calcein efflux by A989T, but in a membrane-based
      assay, organic anion transport by A989T and C1047S was inhibited by MRP1
      modulators as well as wild-type MRP1. GSH accumulation assays suggest cellular
      GSH efflux by A989T and C1047S may be impaired. In conclusion, although six in
      silico analyses consistently predict deleterious consequences of ABCC1 nsSNPs
      G671V, changes in drug resistance and inhibitor sensitivity were only observed
      for A989T and C1047S, which may relate to GSH transport differences. 

PMID- 24080161
TI  - RNA-sequencing quantification of hepatic ontogeny of phase-I enzymes in mice.
AB  - Phase-I drug metabolizing enzymes catalyze reactions of hydrolysis, reduction,
      and oxidation of drugs and play a critical role in drug metabolism. However, the
      functions of most phase-I enzymes are not mature at birth, which markedly affects
      drug metabolism in newborns. Therefore, characterization of the expression
      profiles of phase-I enzymes and the underlying regulatory mechanisms during liver
      maturation is needed for better estimation of using drugs in pediatric patients.
      The mouse is an animal model widely used for studying the mechanisms in the
      regulation of developmental expression of phase-I genes. Therefore, we applied
      RNA sequencing to provide a "true quantification" of the mRNA expression of phase
      I genes in the mouse liver during development. Liver samples of male C57BL/6 mice
      at 12 different ages from prenatal to adulthood were used for defining the
      ontogenic mRNA profiles of phase-I families, including hydrolysis:
      carboxylesterase (Ces), paraoxonase (Pon), and epoxide hydrolase (Ephx);
      reduction: aldo-keto reductase (Akr), quinone oxidoreductase (Nqo), and
      dihydropyrimidine dehydrogenase (Dpyd); and oxidation: alcohol dehydrogenase
      (Adh), aldehyde dehydrogenase (Aldh), flavin monooxygenases (Fmo), molybdenum
      hydroxylase (Aox and Xdh), cytochrome P450 (P450), and cytochrome P450
      oxidoreductase (Por). Two rapidly increasing stages of total phase-I gene
      expression after birth reflect functional transition of the liver during
      development. Diverse expression patterns were identified, and some large gene
      families contained the mRNA of genes that are enriched at different stages of
      development. Our study reveals the mRNA abundance of phase-I genes in the mouse
      liver during development and provides a valuable foundation for mechanistic
      studies in the future. 

PMID- 24080163
TI  - Oxidative damage in young alcohol drinkers: A preliminary study.
AB  - BACKGROUND: Oxidative damage (OD) biomarkers have been used to evaluate metabolic
      stress undergone by alcoholic individuals. In alcoholic patients, these
      biomarkers are usually measured at late stages, i.e., when the alcoholic patients
      are showing clear signs of impaired hepatic function. OD biomarkers are sensitive
      indicators of impaired metabolic function, and might be useful in early stages of
      alcohol consumption to identify individuals who are at greater risk of damage in
      later stages of alcohol consumption. The aim of the present work was to evaluate
      some OD biomarkers in young people at early stages of alcohol consumption.
      METHODS: The study was carried out in a group of young people (18-23 years old)
      who drank alcohol, Youngsters Exposed to Alcohol (YEA) with an average intake of
      118 g of ethanol/week, and a control group (CG) of non-drinkers. Blood counts,
      alcohol dehydrogenase (ADH) activity, glutathione peroxidase (GSH-Px) activity,
      oxidative damage to DNA, and lipid peroxidation were determined in both groups.
      RESULTS: The anthropometric and blood parameters of both groups were similar and
      no clinical symptoms of hepatic damage were observed. Nevertheless, ADH activity,
      lipid peroxidation, and percentage of damaged DNA cells were higher in the YEA
      group than in the control group. In contrast, GSH-Px activity was lower in the
      YEA group than in the control group. CONCLUSION: Alteration in OD biomarkers can
      be found in individuals with 4-5 years of alcohol drinking history. To our
      knowledge, this is the first study giving evidence of OD in individuals at early
      stages of alcohol abuse.

PMID- 24080165
TI  - Novel resorbable glass-ceramic scaffolds for hard tissue engineering: from the
      parent phosphate glass to its bone-like macroporous derivatives.
AB  - One of the major challenges of hard tissue engineering research focuses on the
      development of scaffolds that can match the mechanical properties of the host
      bone and resorb at the same rate as the bone is repaired. The aim of this work
      was the synthesis and characterization of a resorbable phosphate glass, as well
      as its application for the fabrication of three dimensional (3-D) scaffolds for
      bone regeneration. The glass microstructure and behaviour upon heating were
      analysed by X-ray diffraction, differential scanning calorimetry and hot stage
      microscopy. The glass solubility was investigated according to relevant ISO
      standards using distilled water, simulated body fluid (SBF) and Tris-HCl as
      testing media. The glass underwent progressive dissolution over time in all three
      media but the formation of a hydroxyapatite-like layer was also observed on the
      samples soaked in SBF and Tris-HCl, which demonstrated the bioactivity of the
      material. The glass powder was used to fabricate 3-D macroporous bone-like glass
      ceramic scaffolds by adopting polyethylene particles as pore formers: during
      thermal treatment, the polymer additive was removed and the sintering of glass
      particles was allowed. The obtained scaffolds exhibited high porosity (87 vol.%)
      and compressive strength around 1.5 MPa. After soaking for 4 months in SBF, the
      scaffolds mass loss was 76 wt.% and the pH of the solution did not exceed the
      7.55 value, thereby remaining in a physiological range. The produced scaffolds,
      being resorbable, bioactive, architecturally similar to trabecular bone and
      exhibiting interesting mechanical properties, can be proposed as promising
      candidates for bone repair applications.

PMID- 24080164
TI  - In vitro generated Th17 cells support the expansion and phenotypic stability of
      CD4(+)Foxp3(+) regulatory T cells in vivo.
AB  - CD4(+) T cells stimulate immune responses through distinct patterns of cytokine
      produced by Th1, Th2 or Th17 cells, or inhibit immune responses through Foxp3
      expressing regulatory T cells (Tregs). Paradoxically, effector T cells were
      recently shown to activate Tregs, however, it remains unclear which Th subset is
      responsible for this effect. In this study, we found that Th17 cells expressed
      the highest levels of TNF among in vitro generated Th subsets, and most potently
      promoted expansion and stabilized Foxp3 expression by Tregs when co-transferred
      into Rag1(-/-) mice. Both TNF and IL-2 produced by Th17 cells contributed to this
      effect. The stimulatory effect of Th17 cells on Tregs was largely abolished when
      co-transferred with TNFR2-deficient Tregs. Furthermore, Tregs deficient in TNFR2
      also supported a much lower production of IL-17A and TNF expression by co
      transferred Th17 cells. Thus, our data indicate that the TNF-TNFR2 pathway plays
      a crucial role in the reciprocal stimulatory effect of Th17 cells and Tregs. This
      bidirectional interaction should be taken into account when designing therapy
      targeting Th17 cells, Tregs, TNF and TNFR2. 

PMID- 24080166
TI  - Reduction of CuO butterfly wing scales generates Cu SERS substrates for DNA base
      detection.
AB  - We prepare three-dimensional Cu plasmonic structures via a reduction of CuO
      photonic crystals replicated from butterfly wing scales. These Cu superstructures
      with high purity provide surface-enhanced Raman scattering (SERS) substrates for
      the label-free detection of DNA bases down to a micromolar level, which is
      achieved for the first time on Cu and even comparable to the detection
      sensitivity for DNA bases on some Ag substrates. The generation of such
      superstructures has provided a substantial step for the biotemplated SERS
      substrates with high sensitivity, high reproducibility, and ultra-low cost to
      detect biomolecules, and presented affordable high-quality routine SERS
      consumables for corresponding biolaboratories. 

PMID- 24080167
TI  - Novel intergenotype human norovirus recombinant GII.16/GII.3 in Bangladesh.
AB  - Noroviruses (NoVs) are one of the major etiological agents of acute
      gastroenteritis in all age groups. In this study, we identified an intergenotype
      NoV recombinant strain in the fecal specimens of two male infants with acute
      diarrhea in Bangladesh. Phylogenetic analysis showed that the identified strains
      were recombinant NoV strains with a GII.3 capsid and a GII.16 polymerase gene.
      The recombination breakpoint was located in the ORF1/ORF2 overlap region. To the
      best of our knowledge this is the first report of a NoV recombinant GII.16/GII.3
      strain worldwide. 

PMID- 24080168
TI  - Exploring the effect of dentition, dental decay and familiality on oral health
      using metabolomics.
AB  - As a proof of principle, we used an untargeted global metabolic profiling of
      saliva to understand the biochemical processes associated with dental decay,
      dentition (primary and secondary tooth eruption) and familiality in a sample of
      25 sibling pairs. Pairs were selected to represent four different combinations of
      dentition and tooth health: (1) both siblings with primary teeth and no decay
      (n=5); (2) both siblings with primary teeth and discordant for dental decay
      (n=6); (3) both siblings with primary teeth and dental decay (n=4); and (4) one
      sibling with primary teeth the other with mixed dentition and both with no dental
      decay (n=10). There was a strong effect of sibship on the metabolite profiles
      identified; this may reflect the effects of common genes, environment and
      behaviors, and shared oral microbial communities. Nested in the familial effects
      were associations of metabolite profile with dentition and with dental decay.
      Using three different analyses (Euclidean distance, hierarchical clustering and
      PCA using selected biochemicals) metabolite profiles of saliva from children with
      decayed teeth were more similar than the metabolite profiles of saliva from
      children with healthy (sound) teeth. Larger studies that include host behaviors,
      environmental factors, oral microbiota composition and structure, and host
      genetic predisposition are required to identify biomarkers for decay, and to
      estimate the relative contribution of host factors and oral microbes on risk of
      dental decay. 

PMID- 24080169
TI  - Formation and characteristics of aqueous two-phase systems formed by a cationic
      surfactant and a series of ionic liquids.
AB  - Aqueous two-phase systems (ATPS) were obtained in the aqueous mixtures of a
      cationic surfactant and a series of ionic liquids (ILs). The effects of IL
      structure, temperature and additives on the phase separation were systematically
      investigated. The microstructures of some ATPS were observed by freeze-fracture
      replication technique. Lyotropic liquid crystal was found in the bottom phase
      besides micelles under different conditions. Remarkably, both IL structure and
      additives profoundly affected the formation and properties of the ATPSs. The
      phase separation can be attributed to the existence of different aggregates and
      the cation-pi interactions of the cationic surfactant with the ILs, which has a
      significant role in the formation of ATPS. The extraction capacity of the studied
      ATPS was also evaluated through their application in the extraction of two
      biosubstances. The results indicate that the ILs with BF4(-) as anion show much
      better extraction efficiencies than the corresponding ILs with Br(-) as anion do
      under the same conditions. l-Tryptophan was mainly distributed into the NPTAB
      rich phase, while methylene blue and capsochrome were mainly in the IL-rich
      phase. 

PMID- 24080170
TI  - Time to say goodbye to the drug or the model? - why do drugs fail to live up to
      their promise in bile duct ligated mice?

PMID- 24080171
TI  - EIF4G1 R1205H and VPS35 D620N mutations are rare in Parkinson's disease from
      South Africa.
AB  - The R1205H mutation in the eukaryotic translation initiation factor 4G1 (EIF4G1)
      gene and the D620N mutation in the vacuolar protein sorting 35 (VPS35) gene were
      recently found in patients with autosomal dominant or sporadic forms of
      Parkinson's disease (PD). In the present study, 418 South African PD patients and
      528 control subjects of diverse ethnicities were screened using the KASP
      (Kompetitive Allele Specific PCR) genotyping assay. The mutations were not found
      in our study, suggesting that they are not a common cause of PD in South African
      patients. Further studies are needed on the frequency of these 2 mutations in
      other sub-Saharan African populations. 

PMID- 24080172
TI  - Familial frontotemporal dementia associated with C9orf72 repeat expansion and
      dysplastic gangliocytoma.
AB  - A hexanucleotide repeat expansion in the chromosome 9 open reading frame 72 gene
      (C9orf72) was recently identified as the most common genetic cause of
      frontotemporal dementia/amyotrophic lateral sclerosis. Here we describe the
      clinical, pathologic, and genetic features of a Finnish C9orf72 expansion
      carrier, who developed a dysplastic gangliocytoma (Lhermitte-Duclos disease), a
      rare hamartoma/overgrowth syndrome of cerebellar granule cells associated with
      mutations in the phosphatase and tensin homolog gene. In addition to the
      dysplastic gangliocytoma, the patient showed typical transactive response DNA
      binding protein with Mr 43 kD (TDP-43) pathology mainly in the cortex and the
      substantia nigra and numerous p62-positive/TDP-43-negative inclusions in the
      cerebellar granule cells. His sister carried the same gene defect and showed a
      similar type of TDP-43/p62 pathology in her brain. Our findings confirm that the
      clinical and pathologic picture of C9orf72 mutation carriers is more
      heterogeneous than originally thought and warrants further studies on the
      possible involvement of phosphatase and tensin homolog gene pathway in the
      specific cerebellar granule cell pathology associated with C9orf72 expansion. 

PMID- 24080173
TI  - A 2-process model for neuropathology of Alzheimer's disease.
AB  - This study examined relations among neuritic and diffuse plaques, neurofibrillary
      tangles, age, and apolipoprotein E (APOE) in 2 large samples of neuropathology
      cases, the Religious Orders Study and the Memory and Aging Project. Cognitive
      status ranged from normal to demented and AD neuropathology ranged from none to
      severe. Confirmatory factor analysis identified a best-fitting 4-factor solution
      to describe interrelationships among plaques and tangles: a global neuritic
      plaque factor; a global diffuse plaque factor; a factor defined by medial
      temporal neurofibrillary tangles; and a neocortical tangle factor. Results
      supported a hypothesis that neuritic plaques mediate the association of age and
      APOE with neocortical tangles, and similarly mediate the effect of APOE on medial
      temporal tangles. However, medial temporal tangles were related to age
      independent of neuritic plaques. These results support a primary amyloid-based AD
      process that accounts for neocortical tangles and makes the largest contribution
      to medial temporal tangles. A second, age-related but non-amyloid process likely
      contributes to medial temporal lobe tangles. 

PMID- 24080175
TI  - Intracranial pulsatility is associated with regional brain volume in elderly
      individuals.
AB  - Excessive intracranial pulsatility is thought to damage the cerebral
      microcirculation, causing cognitive decline in elderly individuals. We
      investigated relationships between brain structure and measures related to
      intracranial pulsatility among healthy elderly. Thirty-seven stroke-free, non
      demented individuals (62-82 years of age) were included. We assessed brain
      structure, invasively measured cerebrospinal fluid (CSF) pulse pressure, and
      magnetic resonance-quantified arterial and CSF flow pulsatility, as well as
      arterial pulse pressure. Using both multivariate partial least squares and
      ordinary regression analyses, we identified a significant pattern of negative
      relationships between the volume of several brain regions and measures of
      intracranial pulsatility. The strongest relationships concerned the temporal lobe
      cortex and hippocampus. These findings were also coherent with observations of
      positive relationships between intracranial pulsatility and ventricular volume.
      In conclusion, elderly subjects with high intracranial pulsatility display
      smaller brain volume and larger ventricles, supporting the notion that excessive
      cerebral arterial pulsatility harms the brain. This calls for research
      investigating altered intracranial cardiac-related pulsatile stress as a
      potential risk factor that may cause or worsen the prognosis in subjects
      developing cognitive impairment and dementia. 

PMID- 24080174
TI  - Assessment of Parkinson's disease risk loci in Greece.
AB  - Genome-wide association studies (GWAS) have been shown to be a powerful approach
      to identify risk loci for neurodegenerative diseases. Recent GWAS in Parkinson's
      disease (PD) have been successful in identifying numerous risk variants pointing
      to novel pathways potentially implicated in the pathogenesis of PD. Contributing
      to these GWAS efforts, we performed genotyping of previously identified risk
      alleles in PD patients and control subjects from Greece. We showed that
      previously published risk profiles for Northern European and American populations
      are also applicable to the Greek population. In addition, although our study was
      largely underpowered to detect individual associations, we replicated 5 of 32
      previously published risk variants with nominal p values <0.05. Genome-wide
      complex trait analysis revealed that known risk loci explain disease risk in
      1.27% of Greek PD patients. Collectively, these results indicate that there is
      likely a substantial genetic component to PD in Greece, similarly to other
      worldwide populations, that remains to be discovered. 

PMID- 24080176
TI  - No association of the LRRK2 genetic variants with Alzheimer's disease in Han
      Chinese individuals.
AB  - The leucine-rich repeat kinase-2 (LRRK2) gene has been regarded as 1 of the most
      common genetic causes of Parkinson's disease (PD). We hypothesized that LRRK2
      susceptible allele(s) for PD might pose a risk for Alzheimer's disease (AD). In
      this study, we screened 12 LRRK2 gene variants in 2 independent cohorts from
      southwestern China (341 AD patients and 435 normal individuals) and eastern China
      (297 AD patients and 384 normal individuals), to discern the potential
      association between this gene and AD. No variant was identified to be associated
      with AD in either case-control sample. As both of the cohorts were of Han Chinese
      origin, we combined the LRRK2 variant data for the 2 sample sets together (a
      total of 638 AD patients and 819 normal individuals) and still found no
      association between the LRRK2 gene and AD, suggesting that LRRK2 gene variants
      may not affect the development of AD in Han Chinese individuals. 

PMID- 24080177
TI  - Tissue transglutaminase is a biochemical marker for Alzheimer's disease.

PMID- 24080179
TI  - Midwifery care: a perinatal mental health case scenario.
AB  - The establishment of the National Perinatal Depression Initiative (NPDI, 2008
      2013) has brought a focus across Australia for the need to identify women at risk
      of perinatal mental health disorders, suggesting that routine screening by
      relevant health professionals may aid earlier detection, better care and improved
      outcomes. Midwives are frequently the primary point of contact in the perinatal
      period and thus ideally placed to identify, interpret and manage complex
      situations, including screening for perinatal mental health disorders. This paper
      offers strategies that could be implemented into daily midwifery practice in
      order to achieve the goals consistent with the National Perinatal Depression
      Initiative. A case study (Jen) and discussion, guided by recommendations from the
      Australian Nursing and Midwifery Competency standards and beyondblue Clinical
      Practice Guidelines, are used to demonstrate how midwifery care can be provided.
      In accordance with her legal obligations, the midwife should act within her scope
      of practice to undertake a series of psychosocial and medical assessments in
      order to best determine how midwifery care and support can be of benefit to Jen,
      her infant and her family. Suggestions described include administration of
      validated screening questionnaires, clinical interview, physical assessment,
      discussion with partner, awareness of the mother-infant interactions and
      questioning around baby's sleep and feeding. Based on evaluation of the
      information gained from a bio-psycho-social assessment, suggestions are made as
      to the midwifery care options that could be applied. 

PMID- 24080178
TI  - Hippocampal and cortical atrophy in amyloid-negative mild cognitive impairments:
      comparison with amyloid-positive mild cognitive impairment.
AB  - Although patients with amnestic mild cognitive impairment (aMCI) are at higher
      risk of developing Alzheimer's disease (AD), their pathologies could be
      heterogeneous. We aimed to evaluate structural changes in amyloid-negative and
      amyloid-positive aMCI patients. Forty-eight aMCI patients who underwent
      Pittsburgh compound B (PiB) positron emission tomography were recruited. They
      were classified as PiB (-) aMCI (N = 16) and PiB (+) (N = 32). Hippocampal shape
      and regional cortical thickness were compared with 41 subjects with normal
      cognition (NC). Relative to NC, PiB(-) aMCI exhibited hippocampal deformity in
      the right cornu ammonis 1, whereas PiB(+) aMCI exhibited hippocampal deformity in
      bilateral subiculum and cornu ammonis 1 subregions. Relative to NC, PiB(-) aMCI
      showed cortical thinning in the left medial prefrontal and right anterior
      temporal regions, whereas PiB(+) aMCI exhibited cortical thinning in bilateral
      medial temporal regions, temporoparietal junctions and precuneus, and prefrontal
      cortices. Our findings suggest that structural changes in PiB(-) aMCI might be
      due to several possible pathologic changes, whereas structural changes in PiB(+)
      aMCI reflect AD-like structural changes.

PMID- 24080180
TI  - Quantum mechanical investigation of aqueous desferrioxamine B metal complexes:
      trends in structure, binding, and infrared spectroscopy.
AB  - A systematic density functional theory study supported by extended X-ray
      absorption fine structure (EXAFS) and infrared spectroscopic data was conducted
      to elucidate how structure and vibrational spectra of aqueous desferrioxamine B
      (DFOB) metal complexes vary with the metal ion identity. Structural parameters
      derived from EXAFS analyses and trends in metal binding constants are well
      reproduced and validated by the applied computational model. Vibrational mode
      analysis guides determination and recognition of crucial structure- and metal
      sensitive infrared marker bands. The key marker bands, CO and CN stretching
      modes, dominate the infrared spectra in the 1400-1650cm(-1) region. The modes are
      sensitive to the stability and size of the metal core (first coordination shell)
      and indicative of its deformation from the octahedral symmetry. The results shed
      light on the fundamental structural and electronic factors that control metal
      binding by siderophores, and drive their potentially rich and largely unexplored
      interactions with trace metals. 

PMID- 24080181
TI  - Maple leaf (Acer sp.) extract mediated green process for the functionalization of
      ZnO powders with silver nanoparticles.
AB  - The functionalization of ZnO powders with silver nanoparticles (AgNPs) through a
      novel maple leaf extract mediated biological process was demonstrated. Maple leaf
      extract was found to be a very effective bioreduction agent for the reduction of
      silver ions. The reduction rate of Ag(+) into Ag(0) was found to be much faster
      than other previously reported bioreduction rates and was comparable to the
      reduction rates obtained through chemical means. The functionalization of ZnO
      particles with silver nanoparticles through maple leaf extract mediated
      bioreduction of silver was investigated through UV-visible spectrophotometry,
      transmission electron microscopy (TEM), and X-ray diffraction analysis. It was
      found that the ZnO particles were coated with silver nanoparticles 5-20 nm in
      diameter. The photocatalytic ability of the ZnO particles functionalized with
      silver nanoparticles was found to be significantly improved compared to the
      photocatalytic ability of the neat ZnO particles. The silver functionalized ZnO
      particles reached 90% degradation of the dye an hour before the neat ZnO
      particles.

PMID- 24080182
TI  - Simvastatin increases Prolyl-4-Hydroxylase alpha1 expression in atherosclerotic
      plaque and ox-LDL-stimulated human aortic smooth muscle cells via p38 MAPK and
      ERK1/2 signaling.
AB  - Prolyl-4-Hydroxylase alpha1 (P4Halpha1) is essential for collagen synthesis but
      the effect of statin on P4Halpha1 is unknown. We hypothesize that simvastatin may
      increase the expression of P4Halpha1 in atherosclerotic plaques and ox-LDL
      stimulated human aortic smooth muscle cells (HASMCs). In HASMCs, ox-LDL
      suppressed P4Halpha1 expression significantly with peak value occurring at 50
      ug/ml treated for 8h. Ox-LDL also inhibited the expression of type I and III
      collagen and increased the phosphorylation level of p38 MAPK and ERK1/2, but
      blockade or silencing of p38 and ERK1/2 inhibited the suppressive effect of ox
      LDL on P4Halpha1. Then HASMCs were stimulated with or without ox-LDL (50 ug/ml)
      for 8h after simvastatin pretreatment for 1h. Simvastatin significantly
      attenuated the suppressive effect of ox-LDL on P4Halpha1 and collagen production
      by inhibiting ox-LDL uptake and the activation of p38 MAPK and ERK1/2. In
      apolipoprotein E-deficient mice, simvastatin and the inhibitors of p38 and ERK1/2
      significantly increased the stability of the carotid plaques. We also found that
      simvastatin significantly increased the expression of P4Halpha1 and collagen
      possibly due to decreased ox-LDL content and phosphorylation of p38 and ERK1/2 in
      plaques. Thus, simvastatin increases P4Halpha1 and collagen expression in ox-LDL
      stimulated HASMCs and atherosclerotic plaques via p38 MAPK and ERK1/2, thereby
      exerting a plaque stabilizing effect.

PMID- 24080183
TI  - Myocardial glycophagy - a specific glycogen handling response to metabolic stress
      is accentuated in the female heart.
AB  - Cardiac metabolic stress is a hallmark of many cardiac pathologies, including
      diabetes. Cardiac glycogen mis-handling is a frequent manifestation of various
      cardiopathologies. Diabetic females have a higher risk of heart disease than
      males, yet sex disparities in cardiac metabolic stress settings are not well
      understood. Oestrogen acts on key glycogen regulatory proteins. The goal of this
      study was to evaluate sex-specific metabolic stress-triggered cardiac glycogen
      handling responses. Male and female adult C57Bl/6J mice were fasted for 48h.
      Cardiac glycogen content, particle size, regulatory enzymes, signalling
      intermediates and autophagic processes were evaluated. Female hearts exhibited
      51% lower basal glycogen content than males associated with lower AMP-activated
      kinase (AMPK) activity (35% decrease in pAMPK:AMPK). With fasting, glycogen
      accumulated in female hearts linked with decreased particle size and upregulation
      of Akt and AMPK signalling, activation of glycogen synthase and inactivation of
      glycogen phosphorylase. Fasting did not alter glycogen content or regulatory
      proteins in male hearts. Expression of glycogen autophagy marker, starch-binding
      protein-domain-1 (STBD1), was 63% lower in female hearts than males and increased
      by 69% with fasting in females only. Macro-autophagy markers, p62 and LC3BII:I
      ratio, increased with fasting in male and female hearts. This study identifies
      glycogen autophagy ('glycophagy') as a potentially important component of the
      response to cardiac metabolic stress. Glycogen autophagy occurs in association
      with a marked and selective accumulation of glycogen in the female myocardium.
      Our findings suggest that sex-specific differences in glycogen handling may have
      cardiopathologic consequences in various settings, including diabetic
      cardiomyopathy. 

PMID- 24080185
TI  - Electrical behaviour of MEH-PPV based diode and transistor.
AB  - The potential of organic semiconductor based devices for light generation is
      demonstrated by the commercialisation of display technologies using organic light
      emitting diode (OLED). In OLED, organic materials plays an important role of
      emitting light once the current is passed through. However OLED have drawbacks
      whereby it suffers from photon loss and exciton quenching. Organic light emitting
      transistor (OLET) emerged as a new technology to compensate the efficiency and
      brightness loss encountered in OLED. The structure has combinational capability
      to switch the electronic signal such as the field effect transistor (FET) as well
      as to generate light. Different colours of light could be generated by using
      different types of organic material. The light emission could also be tuned and
      scanned in OLET. The studies carried out in this paper focuses on investigation
      of fabricated MEH-PPV based OLED and also OLET via current voltage
      characteristics. These studies will continue with a view to develop an optimised
      MEH-PPV based OLET. 

PMID- 24080184
TI  - Loss of NHE1 activity leads to reduced oxidative stress in heart and mitigates
      high-fat diet-induced myocardial stress.
AB  - Acute inhibition of the NHE1 Na(+)/H(+) exchanger protects against ischemia
      reperfusion injury and chronic inhibition attenuates development of cardiac
      hypertrophy and failure. To determine the cardiac effects of chronic inhibition
      of NHE1 under non-pathological conditions we used NHE1-null mice as a model of
      long-term NHE1 inhibition. Cardiovascular performance was relatively normal in
      Nhe1(-/-) mice although cardiac contractility and relaxation were slightly
      improved in mutant mice of the FVB/N background. GSH levels and GSH:GSSG ratios
      were elevated in Nhe1(-/-) hearts indicating an enhanced redox potential.
      Consistent with a reduced need for antioxidant protection, expression of heat
      shock proteins Hsp60 and Hsp25 was lower in Nhe1(-/-) hearts. Similarly,
      expression of mitochondrial superoxide dismutase 2 was reduced, with no increase
      in expression of other ROS scavenging enzymes. GLUT1 levels were increased in
      Nhe1(-/-) hearts, the number of lipid droplets in myocytes was reduced, and PDK4
      expression was refractory to high-fat diet-induced upregulation observed in wild
      type hearts. High-fat diet-induced stress was attenuated in Nhe1(-/-) hearts, as
      indicated by smaller increases in phosphorylation of Hsp25 and alpha-B
      crystallin, and there was better preservation of insulin sensitivity, as
      evidenced by PKB/Akt phosphorylation. Plasma glucose and insulin levels were
      lower and high-fat diet-induced hepatic lipid accumulation was reduced in Nhe1(-/
      ) mice, demonstrating extracardiac effects of NHE1 ablation. These data indicate
      that long-term ablation of NHE1 activity increases the redox potential, mitigates
      high-fat diet-induced myocardial stress and fatty liver disease, leads to better
      preservation of insulin sensitivity, and may alter both cardiac and systemic
      metabolic substrate handling in mice. 

PMID- 24080186
TI  - Comparative study on human and bovine AT-SC isolation methods.
AB  - Mammalian adipose tissue derived stem cells (AT-SC) have a tremendous potential
      in regenerative medicine for tissue engineering and somatic nuclear transfer
      (SNT). The isolation methods of human and bovine adipose tissue derived stem
      cells are compared in this paper to determine the feasibility and optimum method
      of isolation. The optimum isolation method will reduce the processing time,
      efforts and money as isolation is the first crucial and important step in stem
      cells research. Human abdominal subcutaneous adipose tissue and bovine abdominal
      subcutaneous adipose tissue are digested in three collagenase type 1
      concentration 0.075%, 0.3% and 0.6% agitated at 1 h and 2 h under 37  degrees C
      in 5% CO2 incubator. The cultures are then morphologically characterised. Human
      adipose tissue stem cells are found to be best isolated using abdominal
      subcutaneous depot, using 0.075% collagenase type 1 agitated at 1 h under 37 
      degrees C in CO2 incubator. While bovine adipose tissue derived stem cells are
      best isolated using abdominal subcutaneous depot, using 0.6% collagenase type 1
      agitated at 2 h under 37  degrees C in CO2 incubator. 

PMID- 24080188
TI  - May oxytocin be a trait marker for bipolar disorder?
AB  - There is evidence to suggest that oxytocin is effective in stabilizing mood in
      humans. Lower plasma oxytocin levels have been reported in patients with major
      depression. The objective of this study was to investigate serum oxytocin levels
      during manic and depressive episodes and in the remission period in patients with
      bipolar disorder. Twenty-two patients in manic episode, 21 in depressive episode,
      and 24 in remission at the initial phase, ranging from 18 to 65 years of age, who
      were diagnosed with BD Type I and 24 healthy individuals were included in this
      study. Blood samples were collected from subjects in the morning at the beginning
      of the study. A second blood sampling was obtained from manic and depressive
      patients after response to treatment. MANCOVA was performed to compare the
      oxytocin values of the groups. The serum oxytocin levels of patients in manic
      episode were statistically significantly higher than those of the depressive
      episode and remission groups and of the healthy subjects. The serum oxytocin
      levels of patients in the depressive episode group and in the remission group
      were statistically significantly higher than those of the control group. The
      serum oxytocin levels of the manic episode and depressive episode patients after
      response to treatment were statistically significantly higher than those of the
      control group, and there was no statistically significant difference between the
      patient groups in serum oxytocin levels. The higher oxytocin levels observed in
      patient groups, compared to the controls, before and after response to treatment
      suggest that oxytocin may be a trait marker in BD. 

PMID- 24080187
TI  - Genome-wide association study implicates a novel RNA gene, the lincRNA
      AC068718.1, as a risk factor for post-traumatic stress disorder in women.
AB  - Posttraumatic stress disorder (PTSD) is a common and debilitating mental disorder
      with a particularly high burden for women. Emerging evidence suggests PTSD may be
      more heritable among women and evidence from animal models and human
      correlational studies suggest connections between sex-linked biology and PTSD
      vulnerability, which may extend to the disorder's genetic architecture. We
      conducted a genome-wide association study (GWAS) of PTSD in a primarily African
      American sample of women from the Detroit Neighborhood Health Study (DNHS) and
      tested for replication in an independent cohort of primarily European American
      women from the Nurses Health Study II (NHSII). We genotyped 413 DNHS women - 94
      PTSD cases and 319 controls exposed to at least one traumatic event - on the
      Illumina HumanOmniExpress BeadChip for >700,000 markers and tested 578 PTSD cases
      and 1963 controls from NHSII for replication. We performed a network-based
      analysis integrating data from GWAS-derived independent regions of association
      and the Reactome database of functional interactions. We found genome-wide
      significant association for one marker mapping to a novel RNA gene, lincRNA
      AC068718.1, for which we found suggestive evidence of replication in NHSII. Our
      network-based analysis indicates that our top GWAS results were enriched for
      pathways related to telomere maintenance and immune function. Our findings
      implicate a novel RNA gene, lincRNA AC068718.1, as risk factor for PTSD in women
      and add to emerging evidence that non-coding RNA genes may play a crucial role in
      shaping the landscape of gene regulation with putative pathological effects that
      lead to phenotypic differences. 

PMID- 24080189
TI  - Cortisol reactivity, delay discounting and percent body fat in Chinese urban
      young adolescents.
AB  - The purpose of this study is to test the relation of cortisol reactivity, delay
      discounting and percent body fat (PBF) in adolescents aged 12-13 years (N=87),
      and evaluate the delay discounting as potential components in models of
      adolescent obesity. Anthropometry and body composition measurements were assessed
      in adolescents. The cortisol reactivity to Trier Social Stress Test for Children
      (TSST-C) and delay discounting were measured. The result showed increased
      cortisol reactivity and greater delay discounting were associated with higher PBF
      in girls. Structural equation modeling supported greater delay discounting as a
      mediator of relations between increased cortisol reactivity and PBF in adolescent
      girls. The proposed mediation model indicated that cortisol reactivity is linked
      to PBF through delay discounting, thereby supporting a significant indirect
      relationship. The direct relationship between increased cortisol reactivity and
      higher PBF was significant in a model that did not include delay discounting, and
      was still significant in the mediation model that included delay discounting.
      This study provides the first evidence that greater delay discounting may
      partially account for the relationship of hyperactivity of the HPA-axis and
      higher PBF in girls.

PMID- 24080190
TI  - Lifestyle constraints, not inadequate nutrition education, cause gap between
      breakfast ideals and realities among Japanese in Tokyo.
AB  - Japanese public health nutrition often promotes 'traditional' cuisine. In-depth
      interviews with 107 Japanese adults were conducted in Tokyo from 2009 to 2011,
      using free-listing methods to examine dietary ideals and realities to assess the
      extent to which realities reflect inadequate nutrition education or lifestyle
      constraints. Ideal-reality gaps were widest for breakfast. Most people reported
      Japanese ideals: rice and miso soup were prototypical foods. However, breakfast
      realities were predominantly western (bread-based). While those aged 40-59 were
      more likely to hold Japanese ideals (P=0.063), they were less likely to achieve
      them (P=0.007). All those reporting western ideals achieved them on weekdays,
      while only 64% of those with Japanese ideals achieved them (P<0.001). Partial
      correlations controlling for age and gender showed achievement of Japanese ideals
      were positively correlated with proportion of cooking-related housework, and
      negatively correlated with living standard and income. Ideal menu content was in
      line with current Japanese nutrition advice, suggesting that more nutrition
      education may not change dietary ideals or behavior. Participant-reported reasons
      for ideal-reality discordance demonstrate that work-life balance issues,
      especially lack of time and family structure/life rhythm, are the largest
      obstacles to the attainment of dietary ideals. People reporting 'no time' as a
      primary reason for ideal-reality gaps were less likely to achieve their Japanese
      ideals (odds ratio=0.212). Time realities of people's lives may undermine
      educational efforts promoting Japanese breakfasts. When dietary reality/behavior
      departs from guidelines, it is often assumed that people lack knowledge. If
      ideals are in line with dietary guidelines, then lack of knowledge is not the
      likely cause and nutrition education is not the optimal solution. By asking
      people about the reasons for gaps between their ideals and realities, we can
      identify barriers and design more effective policies and programs to achieve
      dietary ideals. 

PMID- 24080191
TI  - Neurologic injury because of trauma after type II odontoid nonunion.
AB  - BACKGROUND CONTEXT: Treatment of Type II odontoid fractures remains
      controversial, whereas nonoperative treatment is well accepted for isolated Type
      III odontoid fractures. Little is known about long-term sequelae of nonoperative
      management or risk of recurrent injury after nonsurgical treatment. We
      hypothesize that a substantial proportion of odontoid fractures assumed to be
      acute are actually chronic injuries and have a high rate of late displacement
      resulting in neurologic injury. PURPOSE: To identify patients presenting with
      previously unrecognized odontoid fracture nonunions and to document the incidence
      of new neurologic injury after secondary trauma in this population. STUDY DESIGN:
      Retrospective case series. PATIENT SAMPLE: One hundred thirty-three patients with
      Type II odontoid fractures presenting to a Level I trauma center. OUTCOME
      MEASURES: Computed tomography (CT) and magnetic resonance imaging (MRI) scans,
      American Spinal Injury Association Motor Score (AMS), and neurologic examination.
      METHODS: All patients presenting after traumatic injury to a Level I trauma
      center from May 2005 to May 2010 with a Type II odontoid fracture on CT scan were
      included. Patients aged less than 18 years and those with pathologic fractures
      were excluded. Fractures were classified as chronic or acute based on CT evidence
      of chronic injury/nonunion including fracture resorption, sclerosis, and cyst
      formation. Magnetic resonance imaging was then examined for evidence of fracture
      acuity (increased signal in C2 on T2 images). Patients without evidence of acute
      fracture on MRI were considered to have chronic injuries. Computed tomography and
      MRI scans were interpreted independently by two reviewers. Chart review was
      performed to document demographics, AMS, and new-onset neurologic deficit
      associated with secondary injury. RESULTS: One hundred thirty-three patients
      presented with Type II odontoid fractures and no known history of cervical
      fracture with an average age of 79 years. Based on CT criteria, 31/133 (23%)
      fractures were chronic injuries. Nine additional fractures appeared acute on CT
      but were determined to be chronic by MRI findings. The overall number of chronic
      fractures was therefore 40 (30%). Interobserver reliability analysis for
      classification of fractures as chronic demonstrated kappa=0.65 representing
      substantial agreement. Of the 40 chronic fractures, 7 patients (17.5%) had new
      onset neurologic deficits after secondary injury including 4 motor deficits, 2
      sensory deficits, and 1 combined deficit. Although the chronic injury group as a
      whole had similar AMS to the acute injury group (89 vs. 84, p=.27), the seven
      patients with new-onset neurologic deficit had an average AMS of 52.4.
      CONCLUSIONS: A substantial proportion of patients presenting after cervical
      trauma with Type II odontoid fractures have evidence of nonacute injury. Of these
      patients, 17% presented with a new neurologic deficit caused by an "acute-on
      chronic" injury.

PMID- 24080192
TI  - Sizes of the transverse foramina correlate with blood flow and dominance of
      vertebral arteries.
AB  - BACKGROUND CONTEXT: Knowing the side of the dominant vertebral artery (VA) may be
      of utmost importance if the VAs are at risk during spine surgery. Determination
      of the size of VAs is obtained by using Doppler ultrasonography or angiography.
      Because VA is the main anatomic structure occupying the transverse foramina (TF),
      it may be assumed that size of TF and blood flow of VAs should be proportional.
      PURPOSE: To investigate if there is a correlation between the sizes of TF and the
      flow of VAs and determine the diagnostic accuracy of measuring TF to predict
      dominant side of VA. The specific hypothesis was that the larger side of TF
      corresponds to the side of the dominant VA. STUDY DESIGN: This is a
      morphologically based, prospectively designed, single-center study. Thirty
      patients (14 male, 16 female) who were treated for degenerative spinal
      pathologies were included. Patients with cervical fractures, occluded VA,
      prominent degenerative changes affecting TF, deformity, or previous cervical
      instrumentation were excluded from the study. OUTCOME MEASURES: In all patients,
      computed tomography of the cervical spine and Doppler ultrasonography of VAs were
      obtained for morphometric analysis. METHODS: Axial computed tomography cuts at
      the C6 vertebral level were taken. Two measurements were performed for each
      foramen: its right to left width and its anteroposterior depth. Blood flow
      volumes of bilateral VAs were measured using color Doppler. RESULTS: Diameters of
      TF ranged between 2.2 and 7 mm, and its width was generally slightly larger than
      the depth. Transverse foramina were always asymmetric, with no right or left side
      preference. There was a strong correlation between TF diameters and blood flow of
      VAs. Between TF width and VA blood flow, the Pearson correlation coefficient was
      0.59 (p=.001) for right side and 0.72 for left side (p<.0001). The side of the
      larger TF matched with the side of dominant VA in 28 of 30 cases (93.3%)
      (p<.0001). The agreement between the dominant VA and the larger side of TF was
      almost perfect (Kappa=0.087, p<.0001). CONCLUSIONS: There was strong correlation
      between TF diameters and VA blood volume. Our results suggest that TF diameter of
      C6 level can be used to predict the side of the dominant VA reliably.

PMID- 24080193
TI  - Mutational analysis of the Verticillium dahliae protein elicitor PevD1 identifies
      distinctive regions responsible for hypersensitive response and systemic acquired
      resistance in tobacco.
AB  - In our previous study, PevD1 was characterized as a novel protein elicitor
      produced by Verticillium dahliae inducing hypersensitive response (HR) and
      systemic acquired resistance (SAR) in tobacco plants; however, the detailed
      mechanisms of PevD1's elicitor activity remain unclear. In this study, five
      mutant fragments of PevD1 were generated by polymerase chain reaction-based
      mutagenesis and the truncated proteins expressed in Escherichia coli were used to
      test their elicitor activities. Biological activity analysis showed that the N
      terminal and C-terminal of PevD1 had distinct influence on HR and SAR
      elicitation. Fragment PevD1DeltaN98, which spans the C-terminal 57 amino acids of
      PevD1, was critical for the induction of HR in tobacco plants. In contrast,
      fragment PevD1DeltaC57, the N-terminal of 98 amino acids of PevD1, retained the
      ability to induce SAR against tobacco mosaic virus (TMV) but not induction of HR,
      suggesting that the induction of HR is not essential for SAR mediated by PevD1.
      Our results indicated that fragment PevD1DeltaC57 could be a candidate peptide
      for plant protection against pathogens without causing negative effects. 

PMID- 24080194
TI  - Effect of sandblasting and residual stress on strength of zirconia for
      restorative dentistry applications.
AB  - Sandblasting is a commonly used surface treatment technique for dental crowns to
      improve the adhesion of the mating parts of a restoration. The goal of this work
      is to study the effect of different sandblasting conditions on the mechanical
      properties of 3mol% yttria stabilized tetragonal zirconia (3Y-TZP), such as
      biaxial strength, surface elastic modulus, contact hardness and residual stresses
      induced by sandblasting. The specimens were sandblasted considering two different
      particle sizes (110, 250MUm), two pressures (2 and 4bar) and two impact angles
      (30 degrees  and 90 degrees ). Biaxial strength of 3Y-TZP increases when
      sandblasted with 110um particles while its decreases with 250um particles for
      impact angle of 90 degrees . Strength increases slightly when sandblasting with
      30 degrees  impact angle regardless of the size of the particle. Elastic modulus
      and contact hardness were not affected by sandblasting with 110um particles, and
      compressive residual stresses are produced down to a depth of ~10um. 

PMID- 24080195
TI  - Tuning NF-kappaB activity: a touch of COMMD proteins.
AB  - NF-kappaB is an important regulator of immunity and inflammation, and its
      activation pathway has been studied extensively. The mechanisms that downregulate
      the activity of NF-kappaB have also received a lot of attention, particularly
      since its activity needs to be terminated to prevent chronic inflammation and
      subsequent tissue damage. The COMMD family has been identified as a new group of
      proteins involved in NF-kappaB termination. All ten COMMD members share the
      structurally conserved carboxy-terminal motif, the COMM domain, and are
      ubiquitously expressed. They seem to play distinct and non-redundant roles in
      various physiological processes, including NF-kappaB signaling. In this review,
      we describe the mechanisms and proteins involved in the termination of canonical
      NF-kappaB signaling, with a specific focus on the role of the COMMD family in the
      down-modulation of NF-kappaB. 

PMID- 24080196
TI  - Anoctamin 1 dysregulation alters bronchial epithelial repair in cystic fibrosis.
AB  - Cystic fibrosis (CF) airway epithelium is constantly subjected to injury events
      due to chronic infection and inflammation. Moreover, abnormalities in CF airway
      epithelium repair have been described and contribute to the lung function decline
      seen in CF patients. In the last past years, it has been proposed that anoctamin
      1 (ANO1), a Ca(2+)-activated Cl(-) channel, might offset the CFTR deficiency but
      this protein has not been characterized in CF airways. Interestingly, recent
      evidence indicates a role for ANO1 in cell proliferation and tumor growth. Our
      aims were to study non-CF and CF bronchial epithelial repair and to determine
      whether ANO1 is involved in airway epithelial repair. Here, we showed, with human
      bronchial epithelial cell lines and primary cells, that both cell proliferation
      and migration during epithelial repair are delayed in CF compared to non-CF
      cells. We then demonstrated that ANO1 Cl(-) channel activity was significantly
      decreased in CF versus non-CF cells. To explain this decreased Cl(-) channel
      activity in CF context, we compared ANO1 expression in non-CF vs. CF bronchial
      epithelial cell lines and primary cells, in lung explants from wild-type vs.
      F508del mice and non-CF vs. CF patients. In all these models, ANO1 expression was
      markedly lower in CF compared to non-CF. Finally, we established that ANO1
      inhibition or overexpression was associated respectively with decreases and
      increases in cell proliferation and migration. In summary, our study demonstrates
      involvement of ANO1 decreased activity and expression in abnormal CF airway
      epithelial repair and suggests that ANO1 correction may improve this process. 

PMID- 24080197
TI  - Ionizing radiation induced long-term alterations in the adult rat rostral
      migratory stream.
AB  - Ionizing radiation can induce significant injury to normal brain structures. To
      assess radiation-induced late effects, adult male Wistar rats received whole-body
      exposure with fractionated doses of gamma rays (a total dose of 4Gy) and were
      investigated thirty, sixty and ninety days later. Immunohistochemistry and
      confocal microscopy were used to determine the density of neuroblasts derived
      from the anterior subventricular zone (SVZa) and brain resident microglia
      distributed along and/or adjacent to subventricular zone-olfactory bulb axis (SVZ
      OB axis). Cell counting was performed in four anatomical parts along the well
      defined pathway, known as the rostral migratory stream (RMS) represented by the
      SVZa, vertical arm, elbow and horizontal arm of the RMS. Strong overdistribution
      of neuroblasts was seen in the SVZa thirty and sixty days after irradiation
      replaced by a steep decline in the following parts of the RMS and the highest
      decrease ninety days after radiation treatment along the entire SVZ-OB axis.
      Radiation treatment led to a decline or loss of microglia in almost all counted
      parts through the entire experiment. Results showed that ultimate decline of the
      SVZa descendants and loss of microglia suggests a contributory role of reduced
      neurogenesis in the development of radiation-induced late effects. 

PMID- 24080198
TI  - Outcomes of simultaneous resections for patients with synchronous colorectal
      liver metastases.
AB  - INTRODUCTION: The aim of this study was to determine the outcomes associated with
      simultaneous resections compared to patients undergoing sequential resections for
      synchronous colorectal liver metastases. METHOD: Consecutive patients undergoing
      hepatic resections between 2000 and 2012 for synchronous colorectal liver
      metastases were identified from a prospectively maintained database. RESULTS: Of
      the 112 hepatic resections that were performed, 36 were simultaneous resections
      and 76 were sequential resections. There was no difference in disease severity:
      number of metastases (P 0.228), metastatic size (P 0.58), the primary tumour
      nodal status (P 0.283), CEA (P 0.387) or the presence of extra-hepatic metastases
      (P 1.0). Major hepatic resections were performed in 23 (64%) and 60 (79%) of
      patients in the simultaneous and sequential groups respectively (P 0.089). Intra
      operatively no differences were found in blood loss (P 1.0), duration of surgery
      (P 0.284) or number of adverse events (P 1.0). There were no differences in post
      operative complications (P 0.161) or post-operative mortality (P 0.241). The
      length of hospital stay was 14 (95% CI 12.0-18.0) and 18.5 (95% CI 16.0-23.0)
      days in the simultaneous and sequential groups respectively (P 0.03). The 3-year
      overall survival was 75% and 64% in the simultaneous and sequential groups
      respectively (P 0.379). The 3-year hepatic recurrence free survival was 61% and
      46% in the simultaneous and sequential groups respectively (P 0.254). CONCLUSION:
      Simultaneous resections result in similar short-term and long-term outcomes as
      patients receiving sequential resections with comparable metastatic disease and
      are associated with a significant reduction in the length of stay.

PMID- 24080199
TI  - Rapid and safe learning of robotic gastrectomy for gastric cancer:
      multidimensional analysis in a comparison with laparoscopic gastrectomy.
AB  - BACKGROUND: The learning curve of robotic gastrectomy has not yet been evaluated
      in comparison with the laparoscopic approach. We compared the learning curves of
      robotic gastrectomy and laparoscopic gastrectomy based on operation time and
      surgical success. METHODS: We analyzed 172 robotic and 481 laparoscopic distal
      gastrectomies performed by single surgeon from May 2003 to April 2009. The
      operation time was analyzed using a moving average and non-linear regression
      analysis. Surgical success was evaluated by a cumulative sum plot with a target
      failure rate of 10%. Surgical failure was defined as laparoscopic or open
      conversion, insufficient lymph node harvest for staging, resection margin
      involvement, postoperative morbidity, and mortality. RESULTS: Moving average and
      non-linear regression analyses indicated stable state for operation time at 95
      and 121 cases in robotic gastrectomy, and 270 and 262 cases in laparoscopic
      gastrectomy, respectively. The cumulative sum plot identified no cut-off point
      for surgical success in robotic gastrectomy and 80 cases in laparoscopic
      gastrectomy. Excluding the initial 148 laparoscopic gastrectomies that were
      performed before the first robotic gastrectomy, the two groups showed similar
      number of cases to reach steady state in operation time, and showed no cut-off
      point in analysis of surgical success. CONCLUSIONS: The experience of
      laparoscopic surgery could affect the learning process of robotic gastrectomy. An
      experienced laparoscopic surgeon requires fewer cases of robotic gastrectomy to
      reach steady state. Moreover, the surgical outcomes of robotic gastrectomy were
      satisfactory.

PMID- 24080200
TI  - Evolutionarily conserved motifs and modules in mitochondrial protein-protein
      interaction networks.
AB  - Advances in organelle interactomics have led to new insights into organelle
      functions. In this study, we considered the common mitochondrial PIN of four
      evolutionarily distant eukaryotic species, namely Homo sapiens, Mus musculus,
      Drosophila melanogaster and Caenorhabditis elegans. By comparative interactomics
      analysis of mitochondrial PINs in these organisms, five conserved modules were
      identified. Modules comprise the main mitochondrial tasks, including proteins
      involved in translation process, mitochondrial import inner membrane proteins,
      TCA cycle enzymes, mitochondrial electron transport chain, and metabolic enzymes.
      Furthermore, we reemphasize that subgraphs of network, i.e., motifs and themes,
      may represent evolutionarily conserved topological units which are biologically
      significant. 

PMID- 24080201
TI  - [Intramedullary fixation of displaced middle phalangeal neck fractures].
AB  - Middle phalanx neck fracture is an unusual injury. In order to prevent malunion
      and stiffness, a surgical treatment is usually recommended. Owing to the distal
      localization of the fracture, internal fixation is demanding. Open reduction can
      further damage the soft tissues and the bone itself, resulting in stiffness or
      condylar necrosis. The bulk of plate and screws can interfere with the extensor
      apparatus and transarticular or cross K-wires may damage the joint surfaces or
      ligaments. An intramedullary pinning technique is reported minimizing these
      pitfalls. The technique is described and illustrated by two clinical cases with
      good result. 

PMID- 24080202
TI  - Design of triple-shape memory polyurethane with photo-cross-linking of cinnamon
      groups.
AB  - A triple-shape memory polyurethane (TSMPU) with poly(epsilon-caprolactone) -diols
      (PCL-diols) as the soft segments and diphenyl methane diisocyanate (MDI), N,N-bis
      (2-hydroxyethyl) cinnamamide (BHECA) as the hard segments was synthesized via
      simple photo-crosslinking of cinnamon groups irradiated under lambda > 280 nm
      ultraviolet (UV) light. Fourier transform infrared spectroscopy (FT-IR), proton
      nuclear magnetic resonance ((1)H-NMR) and ultraviolet-visible absorption spectrum
      (UV-vis) confirmed the chemical structure of the material. Differential scanning
      calorimetry (DSC) and dynamic mechanical analysis (DMA) results demonstrated that
      the photo-crosslinked polymer possessed two transition temperatures, one is due
      to the melting point of the soft segment PCL-diols, and the other is due to the
      glass transition temperature. All these contributed to the cross-linked structure
      of the hard segments and resulted in an excellent triple-shape memory effect.
      Alamar blue assay showed that the material has good non-cytotoxicity and can be
      potentially used in biomaterial devices. 

PMID- 24080203
TI  - Aquagenic wrinkling of the palms is due to vasoconstriction of palmar skin
      vasculature.
AB  - Aquagenic wrinkling of the palms is an unusual and rare dermatosis characterized
      by rapidly appearing edema, whitish papules, and strong wrinkling of the palms
      after brief immersion in water. Aquagenic wrinkling of the palms is postulated to
      be a result of abnormal electrolyte fluxes that result in sodium retention within
      epidermal keratinocytes and osmotically induced cell volume increases. A clear
      understanding is lacking. It is closely linked to Cystic Fibrosis and has been
      proposed as a test of Cystic Fibrosis but can also be induced by Cyclooxygenase
      (COX-2) inhibitors and Aminoglycosides. Since both aquagenic wrinkling of the
      palms and water immersion wrinkling occur with water immersion, are restricted to
      the glabrous skin, and show features of sympathetic stimulation, I hypothesize
      that aquagenic wrinkling of the palms is part of the spectrum of water immersion
      wrinkling which has recently been shown to be due to sympathetic nervous system
      induced vasoconstriction of the palms and digits. Furthermore I hypothesize that
      both conditions are restricted to the glabrous palmar skin because of unique
      anatomical characteristics. Palmar skin is highly porous to water and contains
      abundant specialized vasculature densely innervated by sympathetic nerves and has
      unique epidermal anchoring for gripping purposes. I postulate that in conditions
      with sweat electrolyte disturbances such as Cystic Fibrosis or drug induced; the
      normal water immersion wrinkling response is exaggerated, leading to the typical
      clinical features of aquagenic wrinkling of the palms. 

PMID- 24080204
TI  - Dromosagnosia, or why some people lose their sense of direction while driving.
AB  - We coined a new word, "dromosagnosia", from the Greek words, dromos ("way,
      road")+agnosia, to describe the loss of direction while driving, an orientation
      disorder similar to but different from pure topographic disorientation.
      Historically, human beings have moved more quickly, from using domesticated
      animals to high speed vehicles, and this may be beyond the brain's ability to
      react. Without the benefit of an automatic navigation system, automobiles are
      associated with more problems of dromosagnosia than are fast-moving aircraft or
      ships. Previous studies have noted that some areas of the brain are associated
      with spatial orientation, spatial memory, and even emotion, and abnormalities
      there could exacerbate the loss of sense of direction. We hypothesize that some
      people are especially disadvantaged from these brain differences and emotional
      disturbances when driving their cars. Functional magnetic resonance imaging
      (fMRI) and event-related potentials (ERP) studies combined with a virtual reality
      driving simulation might be used to find the areas of the brain related to
      dromosagnosia. Future applications: some people with dromosagnosia might benefit
      from special remedial training and a driving safety support system to avoid
      potential problems.

PMID- 24080205
TI  - Identification of suitable reference genes in bone marrow stromal cells from
      osteoarthritic donors.
AB  - Bone marrow stromal cells (BMSCs) are key cellular components for musculoskeletal
      tissue engineering strategies. Furthermore, recent data suggest that BMSCs are
      involved in the development of Osteoarthritis (OA) being a frequently occurring
      degenerative joint disease. Reliable reference genes for the molecular evaluation
      of BMSCs derived from donors exhibiting OA as a primary co-morbidity have not
      been reported on yet. Hence, the aim of the study was to identify reference genes
      suitable for comparative gene expression analyses using OA-BMSCs. Passage 1 bone
      marrow derived BMSCs were isolated from n=13 patients with advanced stage
      idiopathic hip osteoarthritis and n=15 age-matched healthy donors. The expression
      of 31 putative reference genes was analyzed by quantitative reverse transcription
      polymerase chain reaction (qRT-PCR) using a commercially available TaqMan((r))
      assay. Calculating the coefficient of variation (CV), mRNA expression stability
      was determined and afterwards validated using geNorm and NormFinder algorithms.
      Importin 8 (IPO8), TATA box binding protein (TBP), and cancer susceptibility
      candidate 3 (CASC3) were identified as the most stable reference genes. Notably,
      commonly used reference genes, e.g. beta-actin (ACTB) and beta-2-microglobulin
      (B2M) were among the most unstable genes. For normalization of gene expression
      data of OA-BMSCs the combined use of IPO8, TBP, and CASC3 gene is recommended. 

PMID- 24080206
TI  - IQ and adolescent self-harm behaviours in the ALSPAC birth cohort.
AB  - BACKGROUND: Low IQ is associated with an increased risk of suicide and suicide
      attempt in adults, but less is known about the relationship between IQ and
      aspects of suicidal/self-harm behaviours in adolescence. METHODS: We used data
      from the Avon Longitudinal Study of Parents and Children (ALSPAC), a population
      based prospective UK cohort. Binomial and multinomial logistic regression models
      were used to examine the association of IQ measured at age 8 with suicide-related
      outcomes amongst 4810 adolescents aged 16-17 years. RESULTS: There was some
      evidence that associations differed in boys and girls (p values for interaction
      ranged between 0.06 and 0.25). In boys higher IQ was associated with increased
      risk of suicidal thoughts (adjusted odds ratio per 10 point increase in IQ
      score=1.14, 95% Confidence Interval [CI] 1.01-1.28) and suicidal plans (1.15, 95%
      CI 0.93-1.43), although statistical evidence for the latter association was
      limited. There was also evidence for an association with non-suicidal self-harm
      (1.24, 95% CI 1.08-1.45) but not suicidal self-harm (1.04, 95% CI 0.86-1.25). In
      girls higher IQ was associated with increased risk of non-suicidal self-harm
      (1.11, 95% CI 1.02-1.22) but not suicidal thoughts, suicidal plans or suicidal
      self-harm. LIMITATIONS: Loss to follow up and questionnaire non-response may have
      led to selection bias. CONCLUSION: In contrast to previous studies of IQ-suicide
      associations in adults, we found that higher IQ was associated with an increased
      risk of non-suicidal self-harm in male and female adolescents and suicidal
      thoughts in males. Associations of IQ with self-harm differed for self-harm with
      and without suicidal intent, suggesting that the aetiology of these behaviours
      may differ.

PMID- 24080207
TI  - Chemopreventive efficacy of raloxifene, bexarotene, and their combination on the
      progression of chemically induced colon adenomas to adenocarcinomas in rats.
AB  - Estrogen receptor (ER)-beta signaling is associated positively in colon tumor
      progression, whereas downregulation or loss of function of retinoid X receptor
      (RXR)-alpha occurs in colon tumors. The chemopreventive efficacies of the
      estrogen antagonist raloxifene and the selective RXR agonist bexarotene were
      tested individually and in combination, during promotion and progression stages
      of colon tumorigenesis. Colon tumors were induced in male F344 rats with
      azoxymethane and at early adenoma stage, groups of rats (36 or 45 per group) were
      fed diets containing raloxifene (1.5 or 3 ppm), bexarotene (50 or 100 ppm), or
      their low-dose combinations for 40 weeks. Raloxifene or bexarotene alone
      significantly suppressed colon adenocarcinoma formation in terms of
      multiplicities (mean +/- SE): control, 3.59 +/- 0.25; 1.5 ppm raloxifene, 2.51 +/
      0.29 (P < 0.004); 3 ppm raloxifene, 2.14 +/- 0.28 (P < 0.0001); 50 ppm
      bexarotene, 2.25 +/- 0.32 (P < 0.001); 100 ppm bexarotene, 2.1 +/- 0.27 (P <
      0.0001); and 1.5 ppm raloxifene + 50 ppm bexarotene, 1.57 +/- 0.21 (P < 0.0001).
      The low-dose combination caused significant (56%) inhibition of adenocarcinomas
      as compared with control diet fed rats. Tumors exposed to raloxifene, bexarotene
      and/or the combination showed significant suppression of proliferating cell
      nuclear antigen, cyclin D1, and beta-catenin with an increased apoptotic cells (3
      fold) and p21 expression (3.8-fold) as compared tumors of rats fed control diet.
      The combination of low doses of raloxifene and bexarotene significantly
      suppressed the progression of colonic adenomas to adenocarcinomas and may be
      useful for colon cancer prevention and/or treatment in high-risk individuals.

PMID- 24080208
TI  - A highly selective ratiometric visual and red-emitting fluorescent dual-channel
      probe for imaging fluoride anions in living cells.
AB  - Recently, growing attention has been paid to the accurate determination of
      fluoride anion (F(-)) in the environment and living systems for its toxicity and
      biological function investigation. In this paper, we developed a ratiometric
      visual and red-emitting fluorescent dual-channel probe (1) employed Si-O bond as
      a highly selective recognition receptor for imaging F(-) in living cells. Probe 1
      possesses a potential internal charge transfer (ICT) structure, and displays a
      large (158 nm) red-shifted absorption spectrum and the color changes from yellow
      to blue upon addition of F(-) in the aqueous solution. In addition, probe 1 can
      be used to detect F(-) quantitatively by the ratiometric absorption and turn-on
      fluorescence spectroscopy methods with excellent sensitivity. Finally, the
      results of its application to bioimaging of F(-) in living cells show that probe
      1 would be of great benefit to biomedical researchers for investigating the
      effects of fluoride in biological systems.

PMID- 24080209
TI  - An eco-friendly, simple, and sensitive fluorescence biosensor for the detection
      of choline and acetylcholine based on C-dots and the Fenton reaction.
AB  - A simple and novel method is proposed for the preparation of Carbon dots (C-dots)
      with excellent properties. We firstly demonstrated that the fluorescence of C
      dots decreased apparently in the presence of H2O2 and Fe(2+). Based on the this
      finding, C-dots are successfully adopted as probes for the detection of H2O2.
      After the experimental conditions are optimized, the limit of detection (LOD) for
      H2O2 is found to be 0.1 MUM. Furthermore, we established an eco-friendly, simple
      and sensitive biosensor for the detection of choline and acetylcholine (ACh)
      based on the detection of H2O2 using C-dots as probes. The detection limit for
      choline is 0.1 MUM and the linear range is 0.1-40 MUM. The detection limit for
      ACh is found to be 0.5 MUM and the linear range is 0.5-60 MUM. The excellent
      performance of the proposed biosensor shows that this method possesses the
      potential for practical application.

PMID- 24080210
TI  - Rapid and simple G-quadruplex DNA aptasensor with guanine chemiluminescence
      detection.
AB  - Cost-effective and sensitive aptasensor with guanine chemiluminescence detection
      capable of simply quantifying thrombin in human serum was developed using
      thrombin aptamer (TBA), one of the G-quadruplex DNA aptamers, without expensive
      nanoparticles and complicated procedures. Guanines of G-quadruplex TBA-conjugated
      carboxyfluorescein (6-FAM) bound with thrombin do not react with 3,4,5
      trimethoxylphenylglyoxal (TMPG) in the presence of tetra-n-propylammonium
      hydroxide (TPA), whereas guanines of free TBA- and TBA-conjugated 6-FAM
      immobilized on the surface of graphene oxide rapidly react with TMPG to emit
      light. Thus, guanine chemiluminescence in 5% human serum with thrombin was lower
      than that without thrombin when TBA-conjugated 6-FAM was added in two samples and
      incubated for 20 min. In other words, the brightness of guanine chemiluminescence
      was quenched due to the formation of G-quadruplex TBA-conjugated 6-FAM bound with
      thrombin in a sample. High-energy intermediate, capable of emitting dim light by
      itself, formed from the reaction between guanines of TBA and TMPG in the presence
      of TPA, transfers energy to 6-FAM to emit bright light based on the principle of
      chemiluminescence energy transfer (CRET). G-quadruplex TBA aptasensor devised
      using the rapid interaction between TBA-conjugated 6-FAM and thrombin quantified
      trace levels of thrombin without complicated procedures. The limit of detection
      (LOD = background + 3 * standard deviation) of G-quadruplex TBA aptasensor with
      good linear calibration curve, accuracy, precision, and recovery was as low as
      12.3 nM in 5% human serum. Using the technology reported in this research, we
      expect that various types of G-quadruplex DNA aptasensors capable of specifically
      sensing a target molecule such as ATP, HIV, ochratoxin, potassium ions, and
      thrombin can be developed.

PMID- 24080211
TI  - A novel composite of graphene quantum dots and molecularly imprinted polymer for
      fluorescent detection of paranitrophenol.
AB  - A novel fluorescent sensor based on graphene quantum dots (GQDs) was synthesized
      for determination of paranitrophenol (4-NP) in water sample, where molecularly
      imprinted polymer (MIP) was incorporated in GQDs-based sensing system for the
      first time. A simple hydrothermal method was used to fabricate silica-coated
      GQDs. The final composite was developed by anchoring the MIP layer on the silica
      coated GQDs using 3-aminopropyltriethoxysilane as functional monomer and
      tetraethoxysilane as crosslinker. The combination of GQDs and MIP endows the
      composite with stable fluorescent property and template selectivity. Due to
      resonance energy transfer from GQDs (donor) to 4-NP (acceptor), the fluorescence
      of the MIP-coated GQDs composite can be efficiently quenched when 4-NP molecules
      rebound to the binding sites. The composite was applied to the detection of the
      non-emissive 4-NP and exhibited a good linearity in range of 0.02-3.00 ug mL(-1)
      with the detection limit of 9.00 ng mL(-1) (S/N=3). This work may open a new
      possibility for developing GQDs-based composite with selective recognition, and
      it is desirable for chemical sensing application.

PMID- 24080212
TI  - Multiplexed bioactive paper based on GO@SiO2@CeO2 nanosheets for a low-cost
      diagnostics platform.
AB  - In this paper, Graphene oxide@SiO2@CeO2 hybrid nanosheets (GSCs) have been
      successfully synthesized by the wet-chemical strategy. TEM, FITR and XPS were
      applied to characterize the morphology and composition of the nanosheets. The
      colorimetric assay of these nanosheets indicated that they possessed high
      intrinsic peroxidase activity, which should be ascribed to the combination of
      graphene oxide and CeO2. A fully integrated reagentless bioactive paper based on
      GSCs was fabricated, which were able to simultaneously detect glucose, lactate,
      uric acid and cholesterol. The results demonstrated that GSCs have great
      potential as an alternative to the commonly employed peroxidase in daily nursing
      and general physical examination. 

PMID- 24080213
TI  - Improved detection limits of protein optical fiber biosensors coated with gold
      nanoparticles.
AB  - The study presented herein investigates a novel arrangement of fiber-optic
      biosensors based on a tilted fiber Bragg grating (TFBG) coated with noble metal
      nanoparticles, either gold nanocages (AuNC) or gold nanospheres (AuNS). The
      biosensors constructed for this study demonstrated increased specificity and
      lowered detection limits for the target protein than a reference sensor without
      gold nanoparticles. The sensing film was fabricated by a series of thin-film and
      monolayer depositions to attach the gold nanoparticles to the surface of the TFBG
      using only covalent bonds. Though the gold nanoparticle integration had not yet
      been optimized for the most efficient coverage with minimum number of
      nanoparticles, binding AuNS and AuNC to the TFBG biosensor decreased the minimum
      detected target concentrations from 90 nM for the reference sensor, to 11 pM and
      8 pM respectively. This improvement of minimum detection is the result of a
      reduced non-specific absorption onto the gold nanoparticles (by functionalization
      of the external surface of the gold nanoparticles), and of an optical field
      enhancement due to coupling between the photonic modes of the optical fiber and
      the localized surface plasmon resonances (LSPR) of the gold nanoparticles. This
      coupling also increased the sensitivity of the TFBG biosensor to changes in its
      local environment. The dissociation constant (Kd) of the target protein was also
      characterized with our sensing platform and found to be in good agreement with
      that of previous studies.

PMID- 24080214
TI  - Investigation and verification of a bioluminescent biosensor for the quantitation
      of ara-CTP generation: a biomarker for cytosine arabinoside sensitivity in acute
      myeloid leukaemia.
AB  - A novel whole cell bacterial biosensor, which emits light in response to the
      active metabolite of cytosine arabinoside (ara-C, cytarabine), ara-CTP, has been
      investigated and verified. The biosensor has been formulated as an ex vivo assay,
      designed for peripheral blood or bone marrow cells, which can produce a clinical
      result within a working day. The nucleoside analogue ara-C is a key agent for
      treatment of acute myeloid leukaemia (AML); treatment decisions are made rapidly
      with AML, patients often receiving same-day commencement of chemotherapy.
      Currently no rapid predictive test is available to select appropriate therapy for
      patients prior to treatment. Experiments were designed to determine optimal assay
      conditions using leukaemic cell lines. We observed a significant increase (~15
      fold) in bioluminescence signal compared to control after 8-h incubation of the
      biosensor with ara-C. This corresponded to a >2-log increase in light output per
      bacterial cell. Interestingly, bioluminescence conferred a survival advantage to
      the bacteria following ara-C treatment. The assay is sensitive (lower limit of
      quantitation of 0.05 uM), selective, accurate (<= 15% RE) and precise (<= 15%
      coefficient of variation) over a linear concentration range of ara-CTP (0.05-0.5
      uM), and detection is independent of reaction volume. Recovery of added standard
      was tested using ex vivo patient leukaemic cells (n=5). Stability studies on
      lyophilized bacterial biosensor were performed to ensure maintenance of
      performance over 12 months. The biosensor assay could be invaluable to the
      clinician, assisting with treatment selection, and potentially mitigating the
      risks of resistance and toxicity observed with this drug.

PMID- 24080215
TI  - Simultaneous detection of multiple DNA targets based on encoding metal ions.
AB  - We present a novel strategy for simultaneous electrochemical detection of
      multiple DNA targets based on the use of different encoding metal ions as tags.
      The principle of this scheme is that metal ions bound to metallothionein (MT)
      molecules can be released down after hybridization with DNA targets and then be
      detected by stripping voltammetry. The novel detection probes, ssDNA/MT
      conjugates, covered with different metal ions were synthesized for the first
      time, then three encoding metal ions (Zn(2+), Cd(2+), and Pb(2+)) were used to
      differentiate the signals of three virus DNA due to their well-defined anodic
      stripping peaks at -1.13 V (Zn), -0.78 V (Cd), and -0.52 V (Pb) at BiFE,
      respectively. The anodic peak currents increased linearly with the concentrations
      of DNA targets in the range from 0.1 nM to 10nM with a detection limit of 33 pM.
      In addition, the one-base mismatched target was effectively discriminated from
      the complementary target. The described results demonstrated that this method
      possesses high sensitivity and selectivity for multi-target DNA assay and has
      great potential in applications for detection of even more targets in biological
      assays, particularly immunoassays.

PMID- 24080216
TI  - A distance-dependent metal-enhanced fluorescence sensing platform based on
      molecular beacon design.
AB  - A new metal-enhanced fluorescence (MEF) based platform was developed on the basis
      of distance-dependent fluorescence quenching-enhancement effect, which combined
      the easiness of Ag-thiol chemistry with the MEF property of noble-metal
      structures as well as the molecular beacon design. For the given sized AgNPs, the
      fluorescence enhancement factor was found to increase with a d(6) dependency in
      agreement with fluorescence resonance energy transfer mechanism at shorter
      distance and decrease with a d(-3) dependency in agreement with plasmonic
      enhancement mechanism at longer distance between the fluorophore and the AgNP
      surface. As a proof of concept, the platform was demonstrated by a sensitive
      detection of mercuric ions, using thymine-containing molecular beacon to tune
      silver nanoparticle (AgNP)-enhanced fluorescence. Mercuric ions were detected via
      formation of a thymine-mercuric-thymine structure to open the hairpin,
      facilitating fluorescence recovery and AgNP enhancement to yield a limit of
      detection of 1 nM, which is well below the U.S. Environmental Protection Agency
      regulation of the Maximum Contaminant Level Goal (10nM) in drinking water. Since
      the AgNP functioned as not only a quencher to reduce the reagent blank signal but
      also an enhancement substrate to increase fluorescence of the open hairpin when
      target mercuric ions were present, the quenching-enhancement strategy can greatly
      improve the detection sensitivity and can in principle be a universal approach
      for various targets when combined with molecular beacon design.

PMID- 24080217
TI  - Real-time monitoring of bioaerosols via cell-lysis by air ion and ATP
      bioluminescence detection.
AB  - In this study, we introduce a methodology for disrupting cell membranes with air
      ions coupled with ATP bioluminescence detection for real-time monitoring of
      bioaerosol concentrations. A carbon fiber ionizer was used to extract ATP from
      bacterial cells for generating ATP bioluminescence. Our methodology was tested
      using Staphylococcus epidermidis and Escherichia coli, which were aerosolized
      with an atomizer, and then indoor bioaerosols were also used for testing the
      methodology. Bioaerosol concentrations were estimated without culturing which
      requires several days for colony formation. Correlation equations were obtained
      for results acquired using our methodology (Relative Luminescent Unit (RLU)/m(3))
      and a culture-based (Colony Forming Unit (CFU)/m(3)) method; CFU/m(3)=1.8 *
      measured RLU/m(3) for S. epidermidis and E. coli, and CFU/m(3)=1.1 * measured
      RLU/m(3) for indoor bioaerosols under the experimental conditions. Our
      methodology is an affordable solution for rapidly monitoring bioaerosols due to
      rapid detection time (cell-lysis time: 3 min; bioluminescence detection time: <1
      min) and easy operation.

PMID- 24080218
TI  - Concomitant treatment of ureteropelvic junction obstruction and renal calculi
      with robotic laparoscopic surgery and rigid nephroscopy.
AB  - INTRODUCTION: The treatment of ureteropelvic junction obstruction (UPJO) and
      concomitant calculus poses a technically challenging situation. We present our
      experience with using rigid nephroscopy for renal calculi removal during robot
      assisted pyeloplasy (RAP) for UPJO. TECHNICAL CONSIDERATIONS: From December 2010
      to November 2012, 25 patients with UPJO had RAP at our institution; 9 of those
      had concurrent renal calculi, which were simultaneously treated with rigid
      nephroscopy. For stone extraction, a rigid ureteroscope was passed through an
      assistant trocar under laparoscopic vision directly into a previously created
      pyelotomy. The stones were extracted using a rigid grasper or stone basket
      through the rigid ureteroscope. For the removal of the stones within the upper
      and lower calyces, the rigid ureteroscope was introduced into the incised renal
      pelvis through robotic trocars if the "assistant trocar" route failed. Complete
      stone clearance was achieved in 8 of 9 patients. Residual calculi in 1 patient
      were removed with a single session of extracorporeal shock wave lithotripsy. At
      the mean follow-up of 10.2 months, no patients had obstruction or recurrent
      stones. The mean operative time was 187.1 minutes, which was 40.9 minutes longer
      than the mean operative time in patients without renal calculi. There was no
      significant difference in blood loss, hospital stay, complications, and success
      rates between patients with and without renal calculi. CONCLUSION: Our data
      suggest that the use of a concomitant rigid nephroscope and RAP is a safe and
      feasible option for the treatment of UPJO complicated with renal calculi.

PMID- 24080219
TI  - Editorial comment.

PMID- 24080220
TI  - Mature testicular teratoma in children: multifaceted tumors on ultrasound.
AB  - OBJECTIVE: To describe the different ultrasound (US) findings of mature
      testicular hamartomas in children. MATERIALS AND METHODS: This is a retrospective
      study from January 2000 to July 2012 that reviewed the clinical, laboratory, and
      US findings of 7 children with a pathologic diagnosis of mature teratoma of the
      testis. All patients in the study received surgery (tumorectomy or orchiectomy),
      and the material was examined by the institution's Pathology Department. RESULTS:
      The US findings were varied and distinct. As to the lesions' consistency, they
      were cystic (n: 1), multicystic (n: 2), solid-cystic (n: 1), solid containing
      larger or smaller calcifications (n: 2), and focal calcification (n: 1). With
      regard to total circulation, all the solid lesions had few vessels in the
      interior of the lesions. CONCLUSION: Testicular teratoma has a very variable US
      appearance and can simulate that of other lesions. It can be single,
      multiseptated, small, or large. It can contain diffuse or localized
      calcifications. The testicle can have an increased or a normal volume.

PMID- 24080221
TI  - Reply: To PMID 24080222.

PMID- 24080222
TI  - Prostate cancer gene 3 and multiparametric magnetic resonance can reduce
      unnecessary biopsies: decision curve analysis to evaluate predictive models.
AB  - OBJECTIVE: To overcome the well-known prostate-specific antigen limits, several
      new biomarkers have been proposed. Since its introduction in clinical practice,
      the urinary prostate cancer gene 3 (PCA3) assay has shown promising results for
      prostate cancer (PC) detection. Furthermore, multiparametric magnetic resonance
      imaging (mMRI) has the ability to better describe several aspects of PC. METHODS:
      A prospective study of 171 patients with negative prostate biopsy findings and a
      persistent high prostate-specific antigen level was conducted to assess the role
      of mMRI and PCA3 in identifying PC. All patients underwent the PCA3 test and mMRI
      before a second transrectal ultrasound-guided prostate biopsy. The accuracy and
      reliability of PCA3 (3 different cutoff points) and mMRI were evaluated. Four
      multivariate logistic regression models were analyzed, in terms of discrimination
      and the cost benefit, to assess the clinical role of PCA3 and mMRI in predicting
      the biopsy outcome. A decision curve analysis was also plotted. RESULTS: Repeated
      transrectal ultrasound-guided biopsy identified 68 new cases (41.7%) of PC. The
      sensitivity and specificity of the PCA3 test and mMRI was 68% and 49% and 74% and
      90%, respectively. Evaluating the regression models, the best discrimination
      (area under the curve 0.808) was obtained using the full model (base clinical
      model plus mMRI and PCA3). The decision curve analysis, to evaluate the
      cost/benefit ratio, showed good performance in predicting PC with the model that
      included mMRI and PCA3. CONCLUSION: mMRI increased the accuracy and sensitivity
      of the PCA3 test, and the use of the full model significantly improved the
      cost/benefit ratio, avoiding unnecessary biopsies.

PMID- 24080223
TI  - Editorial comment.

PMID- 24080224
TI  - eIF4B and eIF4G jointly stimulate eIF4A ATPase and unwinding activities by
      modulation of the eIF4A conformational cycle.
AB  - Eukaryotic translation initiation factor 4A (eIF4A) is a DEAD-box protein that
      participates in translation initiation. As an ATP-dependent RNA helicase, it is
      thought to resolve secondary structure elements from the 5'-untranslated region
      of mRNAs to enable ribosome scanning. The RNA-stimulated ATPase and ATP-dependent
      helicase activities of eIF4A are enhanced by auxiliary proteins, but the
      underlying mechanisms are still largely unknown. Here, we have dissected the
      effect of eIF4B and eIF4G on eIF4A RNA-dependent ATPase- and RNA helicase
      activities and on eIF4A conformation. We show for the first time that yeast
      eIF4B, like its mammalian counterpart, can stimulate RNA unwinding by eIF4A,
      although it does not affect the eIF4A conformation. The eIF4G middle domain
      enhances this stimulatory effect and promotes the formation of a closed eIF4A
      conformation in the presence of ATP and RNA. The closed state of eIF4A has been
      inferred but has not been observed experimentally before. eIF4B and eIF4G jointly
      stimulate ATP hydrolysis and RNA unwinding by eIF4A and favor the formation of
      the closed eIF4A conformer. Our results reveal distinct functions of eIF4B and
      eIF4G in synergistically stimulating the eIF4A helicase activity in the mRNA
      scanning process. 

PMID- 24080225
TI  - Modes of action of three disinfectant active substances: a review.
AB  - This review deals with three categories of active substances for disinfectant
      products, their modes of action (MOA), and how MOA can help predict propensity
      for resistance in microorganisms. Within the European Union applications for
      approval of disinfectants of all kinds must be submitted in a few years, and
      documentation on MOA and resistance must be part of those applications. Peracetic
      acid is an unspecific, pervasive oxidizer of C-C double bonds and reduced atoms.
      This MOA would imply poor chance for development of resistance in microorganisms,
      as borne out by the absence of such reports in the literature. The quaternary
      ammonium compounds (QAC's) are much more specific in their antimicrobial
      mechanism. Even very low concentrations cause damage to the cytoplasmic membrane
      due to perturbation of the bilayers by the molecules' alkyl chains. Development
      of microbial resistance to QAC's, as well as cross-resistance to antibiotics, are
      particularly well documented. The polymer PHMB is antimicrobial because it
      disturbs the cell membrane's bilayer by interacting with it along the surface of
      the membrane. Resistance to the polymer appears not to develop despite many years
      of use in many fields. However, PHMB's toxicity to humans upon inhalation
      dictates great caution when deploying the substance. 

PMID- 24080226
TI  - [Vitamin D in childhood].
AB  - Infantile Nutritional Rickets has disappeared almost completely in France since
      1992 as vitamin D enriched formula availability and previous vitamin D
      supplementation of infants. The search of evocative symptoms of rickets should be
      a routine procedure in infants, in particular in case of insufficient vitamin D
      intake i.e. breastfeeding, and the possibility of vitamin D resistant rickets.
      Hypocalcaemia occurs not only at the first but also the advanced stages of
      vitamin D deficiency, and may be responsible for severe cardiologic, neurologic
      or respiratory complications with possibility of infant death. For the young
      children between 1 and 5 years and for adolescents, vitamin D insufficiency is
      responsible for poor skeletal mineralization, loss of bone strength, and a
      reduction of peak of bone mineral mass at the end of puberty. The new Dietary
      Reference Intakes (DRI, 2011) increased greatly the Recommended Dietary
      allowances (RDA) from 200 to 600 IU/d (15 MUg/d) for individuals from 1 to 70
      years of age. These levels are not reached in winter, even in countries, like USA
      and Canada, where vitamin D milk fortification is mandatory and others like Japan
      and North-European countries despite high fish consumption. From 1 to 5 years of
      age and during adolescence, a winter vitamin D3 supplementation is necessary with
      80.000 or 100.000 IU periodic loads every 3 months i.e. in November and February.
      In cases of an underlying risk, i.e. insufficient vitamin D photosynthesis in
      summertime (dark skin, wearing heavily skin-covering clothes, or several skin
      diseases), or digestive, renal or nutritional pathologies, use of some drugs,
      loading dose of 80.000 or 100.000 IU, every 3 months should be administered over
      the year.

PMID- 24080227
TI  - Current methods in quantifying ROS and oxidative damage in Caenorhabditis elegans
      and other model organism of aging.
AB  - Accumulation of oxidative damage has been proposed to be causal to aging as
      defined by the Free radical Theory of Aging, which has been subject to recent
      debate. However, a major hurdle in understanding the biological roles of reactive
      oxygen species (ROS) signaling and their oxidative damage has been the widely
      recognized methodological difficulties to measure oxidative damage and ROS in
      vivo. In this review we describe the various novel approaches that have recently
      been developed to overcome this challenge in the nematode Caenorhabditis elegans,
      which is a paradigm invertebrate model organism for studying aging and age
      related disease given its short lifespan, easy genetics and transparency. In
      addition, we also discuss these methods in other important model organisms of
      aging, including the budding yeast Saccharomyces cerevisiae, the fruitfly
      Drosophila melanogaster and the mouse Mus musculus. After an introduction on the
      various ROS that can be encountered, we discuss approaches for the detection and
      quantification of ROS and ROS damage of DNA, lipids and proteins, highlighting
      examples from literature to demonstrate the applicability and caveats of each
      method. As will become clear, combinations of approaches have now become possible
      and will prove essential for thoroughly understanding the involvement of ROS and
      ROS damage in the biology of aging and disease.

PMID- 24080229
TI  - How to adjust for case-mix when comparing outcomes across healthcare providers.

PMID- 24080228
TI  - Chronic alterations in growth hormone/insulin-like growth factor-I signaling lead
      to changes in mouse tendon structure.
AB  - The growth hormone/insulin-like growth factor-I (GH/IGF-I) axis is an important
      stimulator of collagen synthesis in connective tissue, but the effect of
      chronically altered GH/IGF-I levels on connective tissue of the muscle-tendon
      unit is not known. We studied three groups of mice; 1) giant transgenic mice that
      expressed bovine GH (bGH) and had high circulating levels of GH and IGF-I, 2)
      dwarf mice with a disrupted GH receptor gene (GHR-/-) leading to GH resistance
      and low circulating IGF-I, and 3) a wild-type control group (CTRL). We measured
      the ultra-structure, collagen content and mRNA expression (targets: GAPDH, RPLP0,
      IGF-IEa, IGF-IR, COL1A1, COL3A1, TGF-beta1, TGF-beta2, TGF-beta3, versican,
      scleraxis, tenascin C, fibronectin, fibromodulin, decorin) in the Achilles
      tendon, and the mRNA expression was also measured in calf muscle (same targets as
      tendon plus IGF-IEb, IGF-IEc). We found that GHR-/- mice had significantly lower
      collagen fibril volume fraction in Achilles tendon, as well as decreased mRNA
      expression of IGF-I isoforms and collagen types I and III in muscle compared to
      CTRL. In contrast, the mRNA expression of IGF-I isoforms and collagens in bGH
      mice was generally high in both tendon and muscle compared to CTRL. Mean collagen
      fibril diameter was significantly decreased with both high and low GH/IGF-I
      signaling, but the GHR-/- mouse tendons were most severely affected with a total
      loss of the normal bimodal diameter distribution. In conclusion, chronic
      manipulation of the GH/IGF-I axis influenced both morphology and mRNA levels of
      selected genes in the muscle-tendon unit of mice. Whereas only moderate
      structural changes were observed with up-regulation of GH/IGF-I axis, disruption
      of the GH receptor had pronounced effects upon tendon ultra-structure. 

PMID- 24080230
TI  - Assessment of the initial viscoelastic properties of a critical segmental long
      bone defect reconstructed with impaction bone grafting and intramedullary
      nailing.
AB  - INTRODUCTION: This study compared the initial viscoelastic properties of a
      segmental tibial defect stabilized with intramedullary nailing and impaction bone
      grafting to that of a transverse fracture stabilized with intramedullary nailing.
      MATERIALS AND METHODS: Seven sheep tibiae were tested in compression (1000N),
      bending and torsion (6Nm) in a six degree-of-freedom hexapod robot. Tests were
      repeated across three groups: intact tibia (Intact), transverse fracture
      stabilized by intramedullary nailing (Fracture), and segmental defect stabilized
      with a nail and impaction bone grafting (Defect). Repeated measures ANOVA on the
      effect of group on stiffness/phase angle were conducted for each loading
      direction. RESULTS: The Intact group was significantly stiffer than the Fracture
      and Defect groups in bending and torsion (p<0.022 for both loading directions),
      and was marginal for the Defect group in compression (p=0.052). No significant
      differences were found between the Fracture and Defect groups (p>0.246 for all
      loading directions) for stiffness/phase angle. In compression and bending, phase
      angles were significantly greater for the Fracture and Defect groups compared to
      Intact (p<0.025), with no significant differences between groups in torsion
      (p=0.13). Sensitivity analyses conducted between the Fracture and Defect group
      differences found that they were not of clinical significance. CONCLUSION: The
      initial properties of a segmental defect stabilized with intramedullary nailing
      and impaction bone grafting was not clinically significantly different to that of
      a transverse fracture stabilized with intramedullary nailing.

PMID- 24080231
TI  - A reliable method for measuring proximal tibia and distal femur bone mineral
      density using dual-energy X-ray absorptiometry.
AB  - PURPOSE: To assess the intra- and inter-rater reliability of a standardized
      protocol for measuring proximal tibia and distal femur bone mineral density (BMD)
      using dual-energy X-ray absorptiometry (DXA). METHODS: Ten able-bodied
      individuals (7 males) participated in this study. During one measurement session,
      the knee of each participant was scanned twice by rater 1 using DXA. Both scans
      were analyzed twice by rater 1 as well as once by a second rater. Intraclass
      correlation coefficients (ICCs), standard error of measurements (SEMs) and
      smallest detectable differences (SDDs) were calculated for the outcome measures
      proximal tibia and distal femur BMD. A decision study was performed to determine
      the effect of study protocol adjustments (i.e. increasing the number of scan
      repetitions, or scan analyses by the same rater) on SEM and SDD values. RESULTS:
      High intra- and inter-rater ICCs (0.97-0.98) were found for both proximal tibia
      and distal femur BMD. Low SEMs (0.017-0.028 g/cm(2)) and SDDs (0.047-0.077
      g/cm(2)) were found, with a slightly better result for proximal tibia BMD.
      Increasing the number of scan analyses by the same rater did not markedly reduce
      SEM and SDD values, while increasing the number of scan repetitions did.
      CONCLUSIONS: Proximal tibia and distal femur BMD can be reliably assessed with
      this method.

PMID- 24080232
TI  - Error compensation method for improving the accuracy of biomodels obtained from
      CBCT data.
AB  - This paper presents a method of improving the accuracy of the tridimensional
      reconstruction of human bone biomodels by means of tomography, with a view to
      finite element modelling or surgical planning, and the subsequent manufacturing
      using rapid prototyping technologies. It is focused on the analysis and
      correction of the results obtained by means of cone beam computed tomography
      (CBCT), which is used to digitalize non-superficial biological parts along with a
      gauge part with calibrated dimensions. A correction of both the threshold and the
      voxel size in the tomographic images and the final reconstruction is proposed.
      Finally, a comparison between a reconstruction of a gauge part using the proposed
      method and the reconstruction of that same gauge part using a standard method is
      shown. The increase in accuracy in the biomodel allows an improvement in medical
      applications based on image diagnosis, more accurate results in computational
      modelling, and improvements in surgical planning in situations in which the
      required accuracy directly affects the procedure's results. Thus, the subsequent
      constructed biomodel will be affected mainly by dimensional errors due to the
      additive manufacturing technology utilized, not because of the 3D reconstruction
      or the image acquisition technology. 

PMID- 24080234
TI  - Synthesis, characterization, and evaluation of chitosan-complexed starch
      nanoparticles on the physical properties of recycled paper furnish.
AB  - The objectives of the current research were to synthesize and characterize
      chitosan-complexed starch nanoparticles and examine their effect on the physical
      performance of recycled pulp, specifically old corrugated containerboard (OCC).
      This new approach provides a uniquely renewable and useful approach to enhance
      mechanical properties of pulp while maintaining environmental compatibility,
      industrial compatibility, and paper qualities. The starch nanoparticles used for
      the research were prepared from cooked cornstarch gel with ethanol and reacted
      with diethylenetriamine pentaacetic acid (DTPA) in the presence of sodium
      hypophosphite. Thereupon, the DTPA-modified starch nanoparticles (SNs) were
      complexed with chitosan as part of a general chemical strategy to improve their
      incorporation into an OCC matrix and increase interfiber bonding. Spectral
      characterization of the SNs was done using TGA, DSC, FT-IR, and SEM to analyze
      their composition and structure. Approximately 2% chitosan-complexed starch
      nanoparticle derivatives by mass (SNX/C) of OCC-based slurry were thoroughly
      mixed before manufacturing a two-dimensional sheet for physical testing. The
      tensile and burst strength of the modified OCC pulp sheet increased 50 and 49%,
      respectively, albeit having a decreased tear strength compared to the control
      sample. However, when the OCC pulp sheet was coated with a 1% SNX/C by mass
      solution, the tensile and burst strength increased 120 and 70%, respectively,
      while also providing significantly increased gloss, decreased roughness, and tear
      strength. Because the mechanical properties are the most critical property facing
      the recyclability of OCCs, the tremendous gains afforded by the starch
      nanoparticle-DTPA-chitosan proposed give the system enormous potential
      applicability as a viable dry strength agent for paper substrates. 

PMID- 24080233
TI  - Regulatory T cells and vasectomy.
AB  - CD4+ CD25+ regulatory T cells (Tregs) strongly influence the early and late
      autoimmune responses to meiotic germ cell antigens (MGCA) and the gonadal
      immunopathology in vasectomized mice. This is supported by the published and
      recently acquired information presented here. Within 24h of unilateral vasectomy
      (uni-vx) the ipsilateral epididymis undergoes epithelial cell apoptosis followed
      by necrosis, severe inflammation, and granuloma formation. Unexpectedly,
      vasectomy alone induced MGCA-specific tolerance. In contrast, uni-vx plus
      simultaneous Treg depletion resulted in MGCA-specific autoimmune response and
      bilateral autoimmune orchitis. Both tolerance and autoimmunity were strictly
      linked to the early epididymal injury. We now discovered that testicular
      autoimmunity in uni-vx mice did not occur when Treg depletion was delayed by one
      week. Remarkably, this delayed Treg depletion also prevented tolerance induction.
      Therefore, tolerance depends on a rapid de novo Treg response to MGCA exposed
      after vasectomy. Moreover, tolerance was blunted in mice genetically deficient in
      PD-1 ligand, suggesting the involvement of induced Treg. We conclude that pre
      existing natural Treg prevents post-vasectomy autoimmunity, whereas vasectomy
      induced Treg maintains post-vasectomy tolerance. We further discovered that
      vasectomized mice were still resistant to autoimmune orchitis induction for at
      least 12-16 months; thus, tolerance is long-lasting. Although significant sperm
      autoantibodies of low titers became detectable in uni-vx mice at 7 months, the
      antibody titers fluctuated over time, suggesting a dynamic "balance" between the
      autoimmune and tolerance states. Finally, we observed severe epididymal fibrosis
      and hypo-spermatogenesis at 12 months after uni-vx: findings of highly critical
      clinical significance. 

PMID- 24080235
TI  - Hypothesis of homeothermy evolution on isolated South China Craton that moved
      from equator to cold north latitudes 250-200Myr ago.
AB  - Based on avian and mammalian fossils found in the northeastern Chinese province
      of Liaoning and physiological traits linked to homeothermy, a hypothesis of
      evolution of homeothermic animals is proposed. It is based on the importance of
      muscle function in cold environment, as a strong selection pressure that favors
      endothermic metabolism during periods of cold climates. The presented hypothesis
      postulates that in progressively cooling environment, animals will develop
      thermal insulation, increased basal metabolism if food is available, and torpor
      when food is scarce. Since late Permian, Triassic and Cretaceous global
      temperatures were high, an exceptional place that gradually became cold was
      needed for the homeothermy evolution. South China Craton is here proposed as a
      plausible candidate for that role since it drifted across the Paleo-Tethys ocean,
      from equator to high northern latitudes in a journey that lasted from 250 to
      200Myr ago. After this small continent collided with North China Craton some
      200Myr ago, the already cold-adapted animals had spread to large, mostly empty
      spaces on the North China Craton, due to their evolutionary advantage of making
      active living in the cold environment. The most advantageous early homeothermic
      animals went further north to the cold Liaoning to start an oasis that delivered
      modern birds during next 50Myr. Modern mammals possibly evolved somewhere in the
      cold vicinity. This made Liaoning and similarly cold places the cradles of early
      birds and early mammals since for the following millions of years these places
      remained too cold for poikilotherms to enter and warm enough for homeotherms to
      dwell, until the Cretaceous-Paleogene extinction event and subsequent global
      cooling that diminished poikilotherms. Homeothermy was probably even more
      important as a survival advantage in cooler climates of Paleogene, when mammals
      and birds became dominant animals. This interpretation is probably supported by a
      recent report that a small primate Archicebus achilles dated ~55Myr ago was found
      in the more south central China Hubei Province, while Hadrocodium wui, extinct
      mammaliaform that lived 195Myr ago in what is now the Yunnan province in
      southwestern China. The final confirmation of the proposed scenario would be to
      find somewhere in South China avian fossils older than those found in Liaoning,
      or to find the cradle of early mammals somewhere in Northern China. 

PMID- 24080236
TI  - Variation of types of alcoholism: review and subtypes identified in Han Chinese.
AB  - Alcoholism, as it has been hypothesized, is caused by a highly heterogeneous
      genetic load. Since 1960, many reports have used the bio-psycho-social approach
      to subtype alcoholism; however, no subtypes have been genetically validated. We
      reviewed and compared the major single-gene, multiple-gene, and gene-to-gene
      interaction studies on alcoholism published during the past quarter-century,
      including many recent studies that have made contributions to the subtyping of
      alcoholism. Four subtypes of alcoholism have been reported: [1] pure alcoholism,
      [2] anxiety/depression alcoholism, [3] antisocial alcoholism, and [4] mixed
      alcoholism. Most of the important studies focused on three genes: DRD2, MAOA, and
      ALDH2. Therefore, our review focuses on these three genes. 

PMID- 24080238
TI  - [Preauricular lymphadenopathy related to Bartonella henselae].
AB  - INTRODUCTION: Cat scratch disease is characterized by adenitis with usually
      positive outcome. We reported two cases of cat scratch disease with preauricular
      involvement occurring in immunocompetent patients. OBSERVATIONS: Observation 1: a
      28-year-old man had a recent onset of left cervical swelling, with a peripheral
      facial paralysis and liver cytolysis. Serologies for EBV, viral hepatitis, CMV,
      HIV and toxoplasma were negative. Node excision biopsy suggested granulomatous
      lymphadenitis and Bartonella henselae PCR on lymph node was positive. With
      doxycyclin for 3 months, associated with rifampicin for 15 days, abnormal liver
      function disappeared and facial paralysis improved. Observation 2: a 17-year-old
      man had parotid swelling associated with right posterior cervical
      lymphadenopathies associated with fever and profuse sweating. A large right
      preauricular lymphadenopathy with necrotic remodeling was visible on the CT-scan.
      Lymph fluid B. henselae PCR was positive. Positive outcome occurs after surgical
      drainage and short azithromycin treatment. CONCLUSION: Physicians should be aware
      of the rare preauricular localization of cat scratch disease and ask for contact
      with a cat. Parotid tumor localization, lymphoma or tuberculosis should be ruled
      out. Diagnosis is based on the B. henselae PCR. Outcome is often spontaneously
      positive but surgical treatment may be required.

PMID- 24080237
TI  - [Prolonged fever in a 62-year-old man].

PMID- 24080239
TI  - [Acute hepatitis E infection associated with Guillain-Barre syndrome in an
      immunocompetent patient].
AB  - INTRODUCTION: Hepatitis E virus (HEV) infection is now recognized to be an
      emerging autochthonous disease in several countries. There have been several
      reports of neurological manifestations associated with HEV infections.
      Immunocompromised patients seem to be particularly vulnerable. CASE REPORT: We
      report a 73-year-old man who presented with an acute polyradiculopathy and an
      acute hepatitis. HEV RNA was positive in serum and cerebrospinal fluid. Serum
      antiganglioside antibodies were also detected. Liver function tests returned to
      normal rapidly and HEV RNA was undetectable 4 weeks after initial testing. The
      neurological features improved gradually with the use of intravenous
      immunoglobulins. CONCLUSION: We report a case of Guillain-Barre syndrome related
      to acute hepatitis E in an immunocompetent patient. The outcome was favorable
      after intravenous immunoglobulins administration. HEV screening should be
      systematic in patients who present with an acute polyradiculopathy and abnormal
      liver function tests.

PMID- 24080240
TI  - [Causes and differential diagnosis of flush].
AB  - The flush is a transient and recurrent erythema of the upper region of the body,
      due to a sudden arterial dilatation. First, physicians should confirm the flush
      and ascertain the location and timing of skin manifestations. The rapid onset and
      location of the skin rash to the face and anterior chest are the main
      characteristics of flush. In most of the cases, the flush is emotional, but this
      should remain a diagnosis of exclusion, as flush may be the presenting
      manifestation of many systemic or neoplastic disorders. Therefore, a
      comprehensive diagnostic work-up is necessary, including clinical, biological,
      and imaging testing. Neoplastic and endocrine causes of flush include VIPoma,
      carcinoid syndrome, medullary thyroid cancer, mastocytosis, renal cell carcinoma,
      and pheochromocytoma. Mast cell activation syndrome has been recently described,
      but it remains a diagnosis of exclusion. This review will first present the
      different causes of flush, and then will propose a diagnostic algorithm for the
      physician. 

PMID- 24080241
TI  - Successful pulmonary thrombectomy for malignant tumor thrombus after adrenal
      cancer resection.
AB  - A 28-year-old patient presented with a right adrenal mass compressing the right
      kidney and invading the inferior vena cava. The tumor was completely resected;
      however, on a transesophageal echocardiogram intraoperatively, a new pulmonary
      artery thrombus, measuring 1.4 * 1.8 cm, was detected. The patient was therefore
      taken to the operating room the next day. The thrombus was visualized and removed
      and measured 4 * 2 * 1 * 1 cm. The pathology report identified the mass as an
      adrenal tumor thrombus with malignant elements. To our knowledge, this is the
      first known case report of an adrenal tumor thrombus successfully resected at the
      level of the left pulmonary artery.

PMID- 24080242
TI  - Importance of response to neoadjuvant therapy in patients with liver-limited mCRC
      when the intent is resection and/or ablation.
AB  - This review article provides an overview of treatment options for patients with
      liver metastases, with a focus on the importance of response rates on
      resectability. The inclusion of surgery provides the only potential for cure in
      this setting. There are several important surgical considerations for performing
      resections, and close communication between oncologists and surgeons is important
      for achieving the intended outcome. In patients with initially unresectable
      colorectal liver metastases, an association between tumor response rate and
      resection rates has been demonstrated, implying that greater response rates could
      increase resection rates. Neoadjuvant chemotherapy establishes expected response
      rates with the use of biologic agents, such as cetuximab or bevacizumab, further
      improving the response rate and potentially increasing the rate of resection and
      potential to cure the disease.

PMID- 24080243
TI  - Factors affecting the colour of lamb meat from the longissimus muscle during
      display: the influence of muscle weight and muscle oxidative capacity.
AB  - Spectrophotometric measures were used to determine the redness:browness
      (R630/R580) of 4238 lamb longissimus muscle after 3 days under simulated display.
      The results were analysed using linear mixed effects models. Environmental
      factors represented by effects such as kill group and site of production produced
      the greatest variation of up to 2.76 units in R630/R580. Isocitrate dehydrogenase
      activity, reflecting muscle oxidative capacity, reduced R630/R580 by 0.5 units.
      Selection for high muscling sires increased R630/R580 by 0.27 units, likely due
      to changes in muscle oxidative capacity. Lamb carcass weight also increased
      R630/R580 by 0.5 units. Analysis of genotypic factors influencing lamb size and
      growth rate such as sire type and dam breed further supported that increased
      growth rate improves meat R630/R580. Our findings suggest that breeding for
      increased growth rate and increased muscle weight could result in Australian lamb
      meat retaining its red colour for extended periods whilst on display.

PMID- 24080244
TI  - Wading bird guano contributes to Hg accumulation in tree island soils in the
      Florida Everglades.
AB  - Tree islands are habitat for wading birds and a characteristic landscape feature
      in the Everglades. A total of 93 surface soil and 3 soil core samples were
      collected from 7 degraded/ghost and 34 live tree islands. The mean Hg
      concentration in surface soils of ghost tree islands was low and similar to marsh
      soil. For live tree islands, Hg concentrations in the surface head region were
      considerably greater than those in mid and tail region, and marsh soils. Hg
      concentrations in bird guano (286 MUg kg(-1)) were significantly higher than
      those in mammal droppings (105 MUg kg(-1)) and plant leaves (53 MUg kg(-1)). In
      addition, Hg concentrations and delta(15)N values displayed positive correlation
      in soils influenced by guano. During 1998-2010, estimated annual Hg deposition by
      guano was 148 MUg m(-2) yr(-1) and ~8 times the atmospheric deposition.

PMID- 24080245
TI  - Laboratory test interpretations and algorithms in utilization management.
AB  - Appropriate assimilation of laboratory test results into patient care is enhanced
      when pathologist interpretations of the laboratory tests are provided for
      clinicians, and when reflex algorithm testing is utilized. Benefits of algorithms
      and interpretations include avoidance of misdiagnoses, reducing the number of
      laboratory tests needed, reducing the number of procedures, transfusions and
      admissions, shortening the amount of time needed to reach a diagnosis, reducing
      errors in test ordering, and providing additional information about how the
      laboratory results might affect other aspects of a patient's care. Providing
      interpretations can be challenging for pathologists, therefore mechanisms to
      facilitate the successful implementation of an interpretation service are
      described. These include algorithm-based testing and interpretation, optimizing
      laboratory requisitions and/or order-entry systems, proficiency testing programs
      that assess interpretations and provide constructive feedback, utilization of a
      collection of interpretive sentences or paragraphs that can be building blocks
      ("coded comments") for constructing preliminary interpretations, middleware, and
      pathology resident participation and education. In conclusion, the combination of
      algorithms and interpretations for laboratory testing has multiple benefits for
      the medical care for the patient. 

PMID- 24080246
TI  - Lack of functional information explains the poor performance of 'clot load
      scores' at predicting outcome in acute pulmonary embolism.
AB  - Clot load scores have previously been developed with the goal of improving
      prognosis in acute pulmonary embolism (PE). These scores provide a simple
      estimate of pulmonary vascular bed obstruction, however they have not been
      adopted clinically as they have poor correlation with mortality and right
      ventricular (RV) dysfunction. This study performed a quantitative analysis of
      blood flow and gas exchange in 12 patient-specific models of PE, to understand
      the limitations of current clot load scores and how their prognostic value could
      be improved. Prediction of hypoxemia in the models when using estimated baseline
      (non-occluded) minute ventilation and cardiac output correlated closely with
      clinical metrics for RV dysfunction, whereas the clot load score had only a weak
      correlation. The model predicts that large central clots have a greater impact on
      function than smaller distributed clots with the same total clot load, and that
      the partial occlusion of a vessel only has a significant impact on pulmonary
      function when the vessel is close to completely occluded. The effect of clot
      distribution on the redistribution of blood from its normal pattern - and hence
      the magnitude of the potential effect on gas exchange - is represented in the
      model but is not included in current clot load scores. Improved scoring systems
      need to account for the expected normal distribution of blood in the lung, and
      the impact of clot on redistributing the blood flow. 

PMID- 24080247
TI  - Advanced endoscopic imaging techniques in Crohn's disease.
AB  - BACKGROUND: Endoscopy is of pivotal importance in Crohn's disease (CD) patients
      for diagnosis, surveillance and assessment of disease activity and extent. Device
      assisted enteroscopy (DAE) and small-bowel capsule endoscopy (SBCE) have recently
      changed our endoscopic approach to small-bowel imaging. Furthermore, new advanced
      endoscopic imaging techniques have been implemented into clinical practice to
      improve both characterization of mucosal inflammation and detection of dysplastic
      lesions. AIM: To provide readers with a review about the concept of advanced
      endoscopic imaging for the diagnosis and characterization of CD. METHODS: A
      literature search on the use of advanced endoscopy techniques in IBD patients was
      performed. RESULTS: DAE and SBCE allow for deep enteroscopy with high diagnostic
      yields and low complication's rate but their collocation in the diagnostic
      algorithm is still not clearly defined. Dye-based chromoendoscopy (DBC) and
      magnification chromoendoscopy improved dysplasia's detection in long standing
      colitis and prediction of inflammatory activity and extent. Dye-less
      chromoendoscopy (DLC) might offer the potential to replace conventional DBC for
      surveillance. However, both narrow band imaging and i-scan have already shown to
      significantly improve activity and extent assessment in comparison to white-light
      endoscopy. Confocal laser endomicroscopy (CLE) can detect more dysplastic lesions
      in surveillance colonoscopy and predict neoplastic and inflammatory changes with
      high accuracy compared to histology. Moreover, CLE-based molecular imaging may
      anticipate the therapeutic responses to biological therapy. Endocytoscopy can
      identify in vivo inflammatory mucosal cells harboring a new method to assess the
      mucosal activity. CONCLUSIONS: Recent progresses in small-bowel enteroscopy offer
      several potential benefits to improve both diagnosis and characterization of CD.
      New advanced endoscopic imaging techniques can improve detection of dysplasia and
      refine mucosal healing assessment, even looking beyond the morphological
      parameters revealed by conventional endoscopic imaging.

PMID- 24080248
TI  - Crohn's disease and hidradenitis suppurativa. An uncommon association that
      responds to infliximab.

PMID- 24080249
TI  - Novel roles of 1alpha,25(OH)2D3 on DNA repair provide new strategies for breast
      cancer treatment.
AB  - Breast cancers classified as triple-negative (TNBC) and BRCA1-deficient, are
      particularly aggressive and difficult to treat. A major breakthrough was the
      finding that these tumors are exquisitely sensitive to inhibitors of poly(ADP
      ribose) polymerase (PARPi). Phase II clinical trials have shown encouraging
      outcomes, with tolerable side effects. However, a significant fraction of these
      cancers acquire resistance. Elegant studies demonstrated that loss of the DNA
      repair protein 53BP1 contributes to the resistance of BRCA1-deficient cells and
      tumors to PARPi. Thus, raising the levels of 53BP1 in these aggressive tumors
      could potentially restore their sensitivity to PARPi and other genotoxic agents.
      We will review here our studies revealing that 1alpha,25(OH)2D3, an active form
      of vitamin D, stabilizes 53BP1 levels in tumor cells. Breast tumor cells that
      become BRCA1-deficient activate cathepsin L-mediated degradation of 53BP1 to
      ensure genome stability and proliferation. Importantly, 1alpha,25(OH)2D3
      treatment restores the levels of 53BP1 as efficiently as cathepsin L inhibitors,
      which results in increased genomic instability in response to PARPi or radiation,
      and reduced proliferation. Furthermore, analysis of human breast tumors
      identified nuclear cathepsin L as a positive biomarker for TNBC, which correlates
      inversely with 53BP1 when vitamin D receptor (VDR) nuclear levels are low. The
      major findings of these studies are: (1) identification of a new pathway
      contributing to breast cancers with the poorest prognosis; (2) discovery of the
      ability of 1alpha,25(OH)2D3 to inhibit this pathway; and (3) discovery of a
      triple biomarker signature for identification of patients that could benefit from
      the treatment. This article is part of a Special Issue entitled '16th Vitamin D
      Workshop'. 

PMID- 24080250
TI  - Inhibitory effects of Montelukast on mediator release by nasal epithelial cells
      from asthmatic subjects with or without allergic rhinitis.
AB  - AIMS: This study tested inhibitory effects of in vitro Montelukast treatment on
      nasal airway epithelial cells (AEC) cultured from asthmatic patients treated with
      Montelukast with and without concomitant allergic rhinitis. We further examined
      the effect of Montelukast withdrawal in these patients on cytokine release from
      cultured nasal AEC. METHODS: Nasal AEC were collected by brushings from subjects
      with a history of stable (no exacerbations or change in medication for >= 1
      month) physician confirmed mild/moderate asthma whose asthma symptoms were
      documented to benefit from Montelukast treatment (NCT01230437). Release of the
      following mediators by nasal AEC were measured: IL-8, IL-6, IL-10, GM-CSF,
      RANTES, eotaxin and IFN-gamma. Nasal AEC were cultured before and one week after
      withdrawal of their Montelukast treatment. RESULTS: Forty two asthmatics were
      recruited. Nasal AEC were successfully cultured in 17 at the first assessment, 14
      at the second assessment and in 10 individuals at both assessments. Nasal AEC
      release was no different between asthmatics with or without allergic rhinitis.
      Montelukast significantly suppressed the release of IL-8 (p = 0.016), IL-6 (p =
      0.006), RANTES (p = 0.002) and IFN-gamma (p = 0.046), in a dose dependent manner
      in unstimulated cultures but not in those stimulated with IL-1/TNF. Withdrawal of
      Montelukast treatment, was associated with increased IL-8 and RANTES secretion in
      unstimulated nasal AEC cultured from subjects with asthma and allergic rhinitis
      but not with asthma alone. CONCLUSIONS: Montelukast treatment for asthma symptoms
      reversibly suppresses nasal AEC release of pro-inflammatory mediators (i.e. IL-8
      and RANTES) but only in those cells cultured from subjects with concomitant
      allergic rhinitis.

PMID- 24080251
TI  - Primary bone marrow oedema syndromes.
AB  - MRI scanning in patients with rheumatological conditions often shows bone marrow
      oedema, which can be secondary to inflammatory, degenerative, infective or
      malignant conditions but can also be primary. The latter condition is of
      uncertain aetiology and it is also uncertain whether it represents a stage in the
      progression to osteonecrosis in some patients. Patients with primary bone marrow
      oedema usually have lower limb pain, commonly the hip, knee, ankle or feet. The
      diagnosis is one of exclusion with the presence of typical MRI findings.
      Treatment is usually conservative and includes analgesics and staying off the
      affected limb. The natural history is that of gradual resolution of symptoms over
      a number of months. Evidence for medical treatment is limited, but open-label
      studies suggest bisphosphonates may help in the resolution of pain and improve
      radiological findings. Surgical decompression is usually used as a last resort. 

PMID- 24080252
TI  - Bone erosions in patients with chronic gouty arthropathy are associated with
      tophi but not bone oedema or synovitis: new insights from a 3 T MRI study.
AB  - OBJECTIVES: Bone erosion has been linked with tophus deposition in gout but the
      roles of osteitis (MRI bone oedema) and synovitis remain uncertain. Our aims in
      this prospective 3 T MRI study were to investigate the frequency of these
      features in gout and determine their relation to one another. METHODS: 3 T MRI
      scans of the wrist were obtained in 40 gout patients. Scans were scored
      independently by two radiologists for bone oedema, erosions, tophi and synovitis.
      Dual-energy CT (DECT) scans were scored for tophi in a subgroup of 10 patients.
      RESULTS: Interreader reliability was high for erosions and tophi [intraclass
      correlation coefficients (ICCs) 0.77 (95% CI 0.71, 0.87) and 0.71 (95% CI 0.52,
      0.83)] and moderate for bone oedema [ICC = 0.60 (95% CI 0.36, 0.77)]. Compared
      with DECT, MRI had a specificity of 0.98 (95% CI 0.93, 0.99) and sensitivity of
      0.63 (95% CI 0.48, 0.76) for tophi. Erosions were detected in 63% of patients and
      were strongly associated with tophi [odds ratio (OR) = 13.0 (95% CI 1.5, 113)].
      In contrast, no association was found between erosions and bone oedema. Using
      concordant data, bone oedema was scored at 6/548 (1%) sites in 5/40 patients
      (12.5%) and was very mild (median carpal score = 1, maximum = 45). In logistic
      regression analysis across all joints nested within individuals, tophus, but not
      synovitis, was independently associated with erosion [OR = 156.5 (21.2, >999.9),
      P < 0.0001]. CONCLUSION: Erosions were strongly associated with tophi but not
      bone oedema or synovitis. MRI bone oedema was relatively uncommon and low grade.
      These findings highlight the unique nature of the osteopathology of gout.

PMID- 24080253
TI  - The relationship between benign joint hypermobility syndrome and psychological
      distress: a systematic review and meta-analysis.
AB  - OBJECTIVE: This study examines the reported evidence of an association between
      benign joint hypermobility syndrome (BJHS) and psychological symptoms. METHODS: A
      systematic review of published (AMED, CINAHL, MEDLINE, EMBASE, PubMed, Cochrane
      Library) and unpublished research databases (OpenGrey, the World Health
      Organization (WHO) International Clinical Trials Registry Platform, Current
      Controlled Trials, the UK National Research Register Archive) was performed from
      their inception to January 2013. Studies assessing the prevalence and incidence
      of psychological conditions for people diagnosed with BJHS were included. Meta
      analysis assessing the odds ratio (OR) and standardized mean difference in
      severity of psychological conditions was performed. Methodological quality was
      assessed using the Critical Appraisal Skills Programme (CASP) appraisal tools.
      RESULTS: Fourteen papers including 3957 participants, 1006 people with and 2951
      controls without BJHS were eligible. The overall methodological quality was
      moderate. The results indicated that people with BJHS experience significantly
      greater perceptions of fear and more intense fear (P < 0.05) and have a higher
      probability of demonstrating agoraphobia (P < 0.05), anxiety (OR 4.39, 95% CI
      1.92, 10.40), depression (OR 4.10, 95% CI 1.79, 9.41) and panic disorders (OR
      6.72, 95% CI 2.22, 20.35) than those without BJHS (P <= 0.005). Neither anxiety
      nor depression have been assessed in childhood populations. CONCLUSION: People
      with BJHS commonly exhibit a range of symptoms related to anxiety and depression.
      Considerable emotional symptoms accompany BJHS. Further study is warranted to
      explore how these results relate to non-Mediterranean populations and children.
      However, the data suggest that targeting psychological symptoms could be an
      important approach to managing the range of symptoms reported in these patients.

PMID- 24080254
TI  - Macrophage phenotype in the subclinical gut inflammation of patients with
      ankylosing spondylitis.
AB  - OBJECTIVE: Long-term evolution of subclinical gut inflammation to overt Crohn's
      disease (CD) has been described in AS patients. The aim of this study was to
      evaluate macrophage polarization occurring in the inflamed gut of patients with
      AS. METHODS: Twenty-seven HLA-B27(+) AS patients, 20 CD patients and 17 normal
      controls were consecutively enrolled. Classic M1 (iNOS(+)IL-10(-)), resolution
      phase (iNOS(+)IL-10(+)), M2 and CD14(+) macrophages were characterized by
      immunohistochemistry and flow cytometry. Quantitative gene expression analysis of
      IFN-gamma, IL-4, IL-5, IL-33 and STAT6 was performed by real time PCR. RESULTS:
      Classic M1 macrophages were expanded in CD and AS, where resolution phase
      macrophages predominate. A large increase in CD163(+) (M2) macrophages was
      observed in AS strictly correlated with the expression of IL-33, a Th2 cytokine
      involved in M2 polarization. Unlike in CD, CD14(+) macrophages were virtually
      absent in the gut of AS patients and controls. CONCLUSION: The absence of CD14(+)
      macrophages together with the expansion of resolution phase and M2 macrophages is
      the immunological signature of subclinical ileal inflammation in AS.

PMID- 24080255
TI  - Differences in attention and impulsivity between borderline personality disorder
      and bipolar disorder.
AB  - This study aims at investigating attention and impulsivity differences between
      borderline personality disorder and bipolar disorder, as both diseases may share
      neuropsychological deficits. Differential cognitive outcomes on the Continuous
      Performance Test-II were observed between disorders, and also when compared to
      healthy controls. 

PMID- 24080256
TI  - Follicle-stimulating hormone (FSH), current suicidal ideation and attempt in
      female patients with major depressive disorder.
AB  - Current suicidal ideation and attempts are more commonly found in female patients
      with major depressive disorder (MDD) than in males. However, little is known
      about the relationship between activity of female reproductive hormones and
      suicide. The study population consisted of 490 female MDD patients of age >=18.
      They were assessed by the Mini-International Neuropsychiatric Interview. At the
      same visit, we measured blood Follicle-Stimulating Hormone (FSH), Luteinizing
      Hormone (LH), estradiol, progesterone, Adrenocorticotropic Hormone (ACTH),
      cortisol, thyroid hormones, and prolactin. Blood FSH showed a significant
      difference among female MDD patients with suicide attempt, those with ideation,
      and those without within the previous month. Post-hoc analysis also showed that
      FSH was significantly lower in MDD patients with suicide attempt and ideation
      than those without, whereas other hormones showed no differences between those
      with and without attempt. FSH was negatively associated with current suicidality
      scores after adjustment for age and education years in all age groups. FSH was
      significantly lower in those with current suicide ideation or attempt than those
      without in age 45 years or under, but not in other age groups. In conclusion,
      blood FSH is significantly lower in female MDD patients with current suicide
      attempt or ideation than those without, especially in age 45 years or under. 

PMID- 24080257
TI  - Quick evaluation of kinase inhibitors by surface plasmon resonance using single
      site specifically biotinylated kinases.
AB  - In evaluating kinase inhibitors, kinetic parameters such as
      association/dissociation rate constants are valuable information, as are
      equilibrium parameters KD and IC50 values. Surface plasmon resonance (SPR) is a
      powerful technique to investigate these parameters. However, results are often
      complicated because of impaired conformations by inappropriate conditions
      required for protein immobilization and/or heterogeneity of the orientation of
      immobilization. In addition, conventional SPR experiments are generally time
      consuming. Here we introduce the use of single-site specifically biotinylated
      kinases combined with a multichannel SPR device to improve such problems. Kinetic
      parameters of four compounds-staurosporine, dasatinib, sunitinib, and lapatinib
      against six kinases were determined by the ProteOn XPR36 system. The very slow
      off-rate of lapatinib from the epidermal growth factor receptor and dasatinib
      from Bruton's tyrosine kinase and colony stimulating factor 1 receptor (CSF1R)
      were confirmed. Furthermore, IC50 values were determined by an activity-based
      assay. Evaluating both physicochemical and biochemical properties would help to
      understand the detailed character of the compound. 

PMID- 24080258
TI  - A high-throughput-compatible 3D microtissue co-culture system for phenotypic RNAi
      screening applications.
AB  - Cancer cells in vivo are coordinately influenced by an interactive 3D
      microenvironment. However, identification of drug targets and initial target
      validations are usually performed in 2D cell culture systems. The opportunity to
      design 3D co-culture models that reflect, at least in part, these heterotypic
      interactions, when coupled with RNA interference, would enable investigations on
      the phenotypic impact of gene function in a model that more closely resembles
      tumor growth in vivo. Here we describe a high-throughput-compatible method to
      discover cancer gene functions in a co-culture 3D tumor microtissue model system
      composed of human DLD1 colon cancer cells together with murine fibroblasts.
      Strikingly, DLD1 cells in this model failed to expand upon siRNA-mediated
      depletion of Kif11/Eg5, a member of the mitotic kinesin-like motor protein
      family. In contrast, these cancer cells proved to be more resistant to Kif11/Eg5
      depletion when grown as a 2D monolayer. These results suggest that growth of
      certain cancer cells in 3D versus 2D can unveil differential dependencies on
      specific genes for their survival. Moreover, they denote that the high-throughput
      compatible, hanging drop technology-based 3D co-culture model will enable the
      discovery, characterization, and validation of gene functions in key biological
      and pathological processes. 

PMID- 24080259
TI  - Neoclassic drug discovery: the case for lead generation using phenotypic and
      functional approaches.
AB  - Innovation and new molecular entity production by the pharmaceutical industry has
      been below expectations. Surprisingly, more first-in-class small-molecule drugs
      approved by the U.S. Food and Drug Administration (FDA) between 1999 and 2008
      were identified by functional phenotypic lead generation strategies reminiscent
      of pre-genomics pharmacology than contemporary molecular targeted strategies that
      encompass the vast majority of lead generation efforts. This observation, in
      conjunction with the difficulty in validating molecular targets for drug
      discovery, has diminished the impact of the "genomics revolution" and has led to
      a growing grassroots movement and now broader trend in pharma to reconsider the
      use of modern physiology-based or phenotypic drug discovery (PDD) strategies.
      This "From the Guest Editors" column provides an introduction and overview of the
      two-part special issues of Journal of Biomolecular Screening on PDD. Terminology
      and the business case for use of PDD are defined. Key issues such as assay
      performance, chemical optimization, target identification, and challenges to the
      organization and implementation of PDD are discussed. Possible solutions for
      these challenges and a new neoclassic vision for PDD that combines phenotypic and
      functional approaches with technology innovations resulting from the genomics
      driven era of target-based drug discovery (TDD) are also described. Finally, an
      overview of the manuscripts in this special edition is provided. 

PMID- 24080260
TI  - Clinical relevance of target identity and biology: implications for drug
      discovery and development.
AB  - Many of the most commonly used drugs precede techniques for target identification
      and drug specificity and were developed on the basis of efficacy and safety, an
      approach referred to as classical pharmacology and, more recently, phenotypic
      drug discovery. Although substantial gains have been made during the period of
      focus on target-based approaches, particularly in oncology, these approaches have
      suffered a high overall failure rate and lower productivity in terms of new drugs
      when compared with phenotypic approaches. This review considers the importance of
      target identity and biology in clinical practice from the prescriber's viewpoint.
      In evaluating influences on prescribing behavior, studies suggest that target
      identity and mechanism of action are not significant factors in drug choice.
      Rather, patients and providers consistently value efficacy, safety, and
      tolerability. Similarly, the Food and Drug Administration requires evidence of
      safety and efficacy for new drugs but does not require knowledge of drug target
      identity or target biology. Prescribers do favor drugs with novel mechanisms, but
      this preference is limited to diseases for which treatments are either not
      available or suboptimal. Thus, while understanding of drug target and target
      biology is important from a scientific perspective, it is not particularly
      important to prescribers, who prioritize efficacy and safety. 

PMID- 24080261
TI  - The role of the striatum in goal activation of cascaded actions.
AB  - Successful multitasking requires subjects to flexibly activate task goals
      important to accomplish the task at hand. However, the neural mechanisms
      underlying goal activation in multitasking are unknown. Based on neurobiological
      models of action selection, we expected that the extent to which task-goals are
      processed with some overlap that strongly depends on striatal structures.
      Therefore, we applied a stop-change paradigm to examine multitasking using fMRI
      and manipulated the delay between the stop stimulus and the subsequently
      following change signal towards a new GO response (stop-change delay; SCD). The
      manipulation of the SCD was introduced to achieve varying amounts of overlap of
      the two task-goals (stop goal, change goal). This manipulation allowed the
      calculation of a stop-change delay-reaction time function (SCD-RT function), with
      the slope of this function, reflecting on the degree of overlap between the stop
      and the change goal. Data analysis revealed that change trials, independent of
      their SCD, showed an activation pattern encompassing frontal and parietal
      cortical regions. Contrasting the two main SCD (long vs. short SCD) conditions
      with each other showed a stronger BOLD (blood oxygenation level dependent) signal
      activation of the caudate and the right inferior frontal gyrus in trials with a
      long SCD compared to trials with a short SCD. Follow-up analyses showed that
      activation differences of the caudate between the two SCDs drive the effect.
      Integrating the fMRI data with the slope of the SCD-RT function indicated that
      the degree of overlap of stop and change processes is determined by the degree of
      striatal activation on a serial-to-parallel continuum. In conclusion, the
      findings acknowledge the role of the basal ganglia as an important structure
      determining action selection processes via a network of neocortical and striatal
      structures, in terms of an extended multiple demand system. 

PMID- 24080262
TI  - How do shared-representations and emotional processes cooperate in response to
      social threat signals?
AB  - Research in social cognition has mainly focused on the detection and
      comprehension of others' mental and emotional states. Doing so, past studies have
      adopted a "contemplative" view of the role of the observer engaged in a social
      interaction. However, the adaptive problem posed by the social environment is
      first and foremost that of coordination, which demands more of social cognition
      beyond mere detection and comprehension of others' hidden states. Offering a
      theoretical framework that takes into account the dynamical aspect of social
      interaction - notably by accounting for constant interplay between emotional
      appraisal and motor processes in socially engaged human brain - thus constitutes
      an important challenge for the field of social cognition. Here, we propose that
      our social environment can be seen as presenting opportunities for actions
      regarding others. Within such a framework, non-verbal social signals such as
      emotional displays are considered to have evolved to influence the observer in
      consistent ways. Consequently, social signals can modulate motor responses in
      observers. In line with this theoretical framework we provide evidence that
      emotional and motor processes are actually tightly linked during the perception
      of threat signals. This is ultimately reflected in the human brain by constant
      interplay between limbic and motor areas. 

PMID- 24080263
TI  - Immediate effects of exposure to positive and negative emotional stimuli on
      visual search characteristics in patients with unilateral neglect.
AB  - The performance of patients with unilateral neglect (UN) in tasks demanding
      visual attention is characterized by contralesional disadvantage which is
      markedly unstable in magnitude. Such instability of the attentional system is
      seen very clearly in clinical practice and thus far has no satisfying
      explanation. Here we examined the immediate effect of exposure to non-lateralized
      emotional stimuli on UN patients' attentional bias and performance variability.
      We tested eight right-hemisphere damaged stroke patients with left-sided neglect
      and eight age-matched healthy subjects in a visual conjunction-search task, each
      trial performed immediately after viewing a centrally-presented picture, which
      was emotionally negative, positive or neutral. Both performance bias and
      variability in performing the search task was analyzed as a function of the
      valence of the picture, and a method for analyzing reaction time (RT) variance in
      a small sample is introduced. Overall, UN subjects, but not controls, were slower
      and more variable in their RT for left- compared to right-sided targets. In the
      UN group, detecting left-sided targets was significantly slower in trials that
      followed presentation of negative pictures as compared to positive pictures,
      regardless of the fact that both picture types were judged as equally arousing by
      the patients. Moreover, UN patients exhibited larger performance variance on the
      left then on the right, and negative emotional stimuli were associated with
      larger variance asymmetry than positive emotional stimuli. Examining the
      coefficient of variation pointed to a possible dissociation between the effects
      of emotional stimuli on the lateralized RT mean (reflecting attentional bias) and
      on the lateralized RT variance (reflecting system instability). We conclude that
      emotional stimuli affect the spatial imbalance of both performance speed and
      stability in UN patients. 

PMID- 24080264
TI  - Metabolomics evaluation of the effects of green tea extract on acetaminophen
      induced hepatotoxicity in mice.
AB  - Green tea has been purported to have beneficial health effects including
      protective effects against oxidative stress. Acetaminophen (APAP) is a widely
      used analgesic drug that can cause acute liver injury in overdose situations.
      These studies explored the effects of green tea extract (GTE) on APAP-induced
      hepatotoxicity in liver tissue extracts using ultra performance liquid
      chromatography/quadrupole time-of-flight mass spectrometry and nuclear magnetic
      resonance spectroscopy. Mice were orally administered GTE, APAP or GTE and APAP
      under three scenarios. APAP alone caused a high degree of hepatocyte necrosis
      associated with increases in serum transaminases and alterations in multiple
      metabolic pathways. The time of GTE oral administration relative to APAP either
      protected against or potentiated the APAP-induced hepatotoxicity. Dose dependent
      decreases in histopathology scores and serum transaminases were noted when GTE
      was administered prior to APAP; whereas, the opposite occurred when GTE was
      administered after APAP. Similarly, metabolites altered by APAP alone were less
      changed when GTE was given prior to APAP. Significantly altered pathways included
      fatty acid metabolism, glycerophospholipid metabolism, glutathione metabolism,
      and energy pathways. These studies demonstrate the complex interaction between
      GTE and APAP and the need to employ novel analytical strategies to understand the
      effects of dietary supplements on pharmaceutical compounds. 

PMID- 24080265
TI  - A giant cystic leiomyoma mimicking an ovarian malignancy.
AB  - INTRODUCTION: Leiomyoma of the uterus is the most common type of tumor affecting
      the female pelvis and arises from uterine smooth muscle. The size of leiomyomas
      varies from microscopic to giant; giant myomas are exceedingly rare. We report an
      unusual case of a large, cystic, pedunculated uterine leiomyoma mimicking a
      primary malignant ovarian tumor on sonography and CT. PRESENTATION OF CASE: A 58
      year-old postmenopausal nulliparous woman presented with a history of lower
      abdominal pain and distension for a period of approximately 12 months. The
      patient's personal history revealed difficulty in walking, tiredness and recent
      weight gain of approximately 25kg. Sonography and CT examination showed a large
      mass that filled the abdomen. A preoperative diagnosis of a primary malignant
      ovarian tumor was made. The patient underwent laparotomy, total hysterectomy and
      bilateral salpingo-ooferectomy. The histology revealed a leiomyoma with extensive
      cystic degeneration. DISCUSSION: The current established management of uterine
      fibroids may involve expectant, surgical, or medical management or uterine artery
      embolization or a combination of these treatments. A surgical approach is
      preferred for management of giant leiomyomas. CONCLUSION: Pedunculated leiomyomas
      should be considered in the differential diagnosis of a multilocular and
      predominantly cystic adnexal mass.

PMID- 24080266
TI  - Role of Art v 3 in pollinosis of patients allergic to Pru p 3.
AB  - BACKGROUND: Food allergy caused by lipid transfer protein (LTP) from peach (Pru p
      3) is frequently associated with sensitization to mugwort LTP (Art v 3). Although
      in vitro cross-reactivity is already well known, it has yet to be elucidated
      whether a pollen LTP can induce rhinitis. OBJECTIVE: The aim of this study was to
      investigate whether mugwort LTP could elicit respiratory symptoms and whether a
      primary food LTP allergy could lead to a respiratory allergy. METHODS: Patients
      with confirmed Pru p 3 allergy and control subjects were selected. Immediate
      responses to nasal allergen provocation tests (NAPTs) with Art v 3, Pru p 3, and
      mugwort were assessed by using the visual analog scale score, total nasal symptom
      score, and acoustic rhinometry. Tryptase and cysteinyl leukotriene (cysLT) levels
      were measured in nasal lavage fluid. Immunoblotting, ELISAs, and ELISA inhibition
      assays were also performed. RESULTS: Fifteen patients and 9 control subjects were
      selected. NAPT results with Art v 3 and Pru p 3 showed significant changes in
      acoustic rhinometry, visual analog scale scores, total nasal symptom scores, and
      cysLT levels (P < .001). Tryptase levels were only increased in NAPTs with Pru p
      3. NAPTs with mugwort were used in those patients who were only sensitized to Art
      v 3, with similar results (P < .05). No significant changes were detected in
      control subjects. CONCLUSION: The results demonstrated that a pollen LTP can
      elicit rhinitis in sensitized patients. Findings also suggest that a primary
      sensitization to Pru p 3 can lead to a respiratory allergy through cross
      reactivity.

PMID- 24080267
TI  - Assessing nursing student intent for PHD study.
AB  - BACKGROUND: Nursing faculty shortages threaten a country's ability to produce the
      amount of nurses necessary to sustain the delivery of healthcare services.
      Programs that "fast track" graduate education options for registered nurses are
      one solution to the problem. OBJECTIVES: To (1) evaluate admission criteria into
      PhD programs for direct entry from a bachelor's degree; (2) ascertain bachelors
      and masters degree nursing students' perspectives on pursuing a BSN to PhD course
      of study; (3) clarify factors that influence students' decision-making processes
      behind pursuing a PhD and identify characteristics of those who would be likely
      recruits for PhD study; 4) to test the survey questions to develop an instrument
      for future use. DESIGN: A cross-sectional pilot study. SETTING: A nursing program
      at a large urban university in the United States of America with an enrollment of
      over 1400 students. PARTICIPANTS: Currently enrolled bachelor's, master's, and
      doctor of nursing practice students. METHODS: Students were sampled via a 10
      question (including one open-ended question) electronic mail survey that included
      1385 eligible subjects. RESULTS: Among the 606 respondents (57% response rate),
      63% were between ages 18 and 30 and 87% indicated that full tuition funding with
      a living stipend would make them more interested in pursuing a PhD. Current
      program track was a significant predictor of course of study and area of interest
      (p=.029). Analysis of the 427 respondents to the open-ended question revealed
      themes around "time" and "money" as the main barriers to study. The desire to
      gain clinical experience prior to PhD study was the third theme and an
      unanticipated finding. CONCLUSIONS: The questionnaire offered some predictive
      ability for gauging intent to study for a PhD among bachelor's and graduate
      degree prepared nurses. The results do offer some suggestions for nursing
      workforce development to help address faculty shortages.

PMID- 24080268
TI  - Evaluation of an online continuing education program from the perspective of new
      graduate nurses.
AB  - The aim of this study is to evaluate the online continuing education program from
      the perspectives of new graduate nurses. An evaluation framework includes five
      factors (program and course structure, course materials, technology, support
      services and assessment). In this study, descriptive research methods were used.
      Participants of the study included 2.365 registered nurses enrolled in the first
      online nursing bachelor completion degree program in the country. Data were
      collected by survey. The findings indicated that students were mostly satisfied
      with this program. The results of this study suggest that well designed
      asynchronous online education methods can be effective and appropriate for
      registered nurses. However, the provision of effective support and technological
      infrastructure is as vital as the quality of teaching for online learners. 

PMID- 24080269
TI  - Attitudes of nursing students toward people with disabilities.
AB  - BACKGROUND: Attitudes of healthcare professionals are major factors in the
      rehabilitation and self-acceptance of people with disabilities. Consequently, it
      is important that nurses develop or maintain positive attitudes towards people
      with disabilities during their education. Nevertheless, more knowledge is needed
      about current attitudes of nursing students and factors influencing these
      attitudes. OBJECTIVES: To investigate the attitude of Turkish nursing students
      towards people with disabilities and demographic variables mostly influence this
      attitude. PARTICIPANTS: The sample of the study comprised of 587 undergraduate
      nursing students. DESIGN AND SETTING: This descriptive study was conducted at two
      nursing schools and two health schools at undergraduate level located in three
      different cities in Turkey. METHOD: Data were collected in a class composed of
      students from schools between January and April 2009. The questionnaire used in
      the study consisted of four parts: (1) a demographic data sheet; (2) background
      in disability (3) contact and experiences with disabled people (4) The Attitudes
      Toward Disabled Persons Scale (ATDP-form O). RESULTS: All of the participants
      were female with a mean age of 22.25 +/- 1.53. Only 2% of the participants
      reported having a physical disability themselves. The mean ATDP score was 64.27
      +/- 0.36 (range 33-96). The age, school type, prior knowledge, giving care to
      disabled people in the family and social life were found statistically
      significant factors for having positive attitudes (p<0.05). CONCLUSIONS: The age
      group, type of school, prior education regarding the disabled and the condition
      of caregiving to disabled people are factors influencing nursing students'
      attitudes towards people with disabilities.

PMID- 24080270
TI  - Keeping our nursing and midwifery workforce: factors that support non-practising
      clinicians to return to practice.
AB  - BACKGROUND: Within Australia and internationally (Health Workforce Australia,
      2012) an increasing and on-going nursing workforce shortage is documented. Recent
      international estimates indicate that there will be ongoing and significant gaps
      in the supply of a nursing workforce; the United Kingdom is predicted to have a
      reduction of 12.12% nurses over the coming eight years if a current 'steady
      state' is maintained (Buchan and Seacombe, 2011); Canada is predicted to have a
      shortage of 60,000 nurses by 2022 (Tomblin et al., 2012) with Australia's
      anticipated nursing shortage reported as over 90,000 by the year 2025 (Health
      Workforce Australia, 2012). Queensland Health in response to their tracked
      emerging nursing and midwifery workforce shortages developed a nursing and
      midwifery refresher programme to return registered staff back to the workforce. A
      study was undertaken between 2008 and 2010 to provide an understanding of how non
      practising nurses and midwives maybe supported back into the workforce. METHODS:
      Programme applicants (444) were invited to respond to an on-line survey designed
      to understand what aspects of the programme supported their learning and ability
      to return to the workforce. This number represents those who applied but not all
      completed or commenced the programme. Descriptive statistics (Polit and Beck,
      2008) were used to collate quantifiable survey responses and free text and
      unsolicited responses were themed. RESULTS: The survey received a 35.5% response
      rate (n=158) with a return of 20% of unsolicited comments in the form of e-mail
      responses which were included in the themed results. Key themes supporting
      participants' learning and ability to return to the workforce were: Respondents
      were 94% female and 6% male, with 37.7% >51 years of age. Child rearing was the
      foremost reason for female staff relinquishing workforce roles (36.6%). The
      primary reason for returning to the workforce was maintenance of registration
      (40.5%). Both theory and clinical placement components were seen by participants
      as contributing to their confidence to return to the health workforce.
      CONCLUSION: The Queensland Nursing and Midwifery Refresher Programs provided a
      structured programme for registered, non-practising nurses and midwives to return
      to the Queensland Health workforce. Responses indicated that clinical supervision
      and contract learning should be central to a return to workforce induction
      programme for registered but non-practising nurses and midwives. The majority of
      nurses and midwives returning to the workforce were approaching retirement age in
      10-15 years.

PMID- 24080271
TI  - Children's sleep disturbance scale in differentiating neurological disorders.
AB  - BACKGROUND: We use the Sleep Disturbance Scale for Children (SDSC) routinely as a
      tool for evaluating children's sleep quality in our pediatric neurology clinic.
      We analyzed at its ability to detect sleep disturbances distinctive to selected
      neurological disorders. PATIENTS: One-hundred and eighty-six children (age range
      2-18 years) who were evaluated by the SDSC questionnaire were divided into three
      groups according to their principal diagnosis: epilepsy, attention deficit
      hyperactivity disorder, or others. Their responses were analyzed. RESULTS: The
      average frequency of abnormal total sleep score was 26.9%. The most frequent
      sleep disorders were excessive somnolence (25.3%), initiating and maintaining
      sleep (24.7%), and arousal/nightmares (23.1%). There were no significant group
      differences for total scores or sleep disorder-specific scores; although a sleep
      wake transition disorder was more frequent among children with epilepsy (31%). A
      literature search revealed that the frequency of abnormal total scores in several
      neurological disorders (e.g., epilepsy, cerebral palsy) ranges between 20% and
      30%. CONCLUSIONS: The mechanism underlying sleep disturbances in many
      neurological disorders may be unrelated to that of the primary disease but rather
      originate from nonspecific or environmental factors (e.g., familial/social
      customs and habits, temperament, psychological parameters). Although the SDSC is
      noninformative for studying the effect of a specific neurological disorder on
      sleep, we still recommend its implementation for screening for sleep disturbances
      in children with neurological abnormalities.

PMID- 24080272
TI  - Pattern of restricted diffusion seen on magnetic resonance imaging in maple syrup
      urine disease.

PMID- 24080273
TI  - Reversible white matter lesions during ketogenic diet therapy in glucose
      transporter 1 deficiency syndrome.
AB  - BACKGROUND: Glucose transporter type 1 deficiency syndrome is caused by brain
      energy failure resulting from a disturbance in glucose transport. PATIENTS: We
      describe a 4-year-old boy with classical type glucose transporter type 1
      deficiency syndrome with a heterozygous splice acceptor site mutation (c.517
      2A>G) in the SLCA2A1 gene. RESULTS: We initiated a ketogenic diet at 4 months of
      age. However, even though his condition was good during ketogenic diet therapy,
      multiple cerebral white matter and right cerebellum lesions appeared at 9 months
      of age. The lesions in the cerebral white matter subsequently disappeared,
      indicating that white matter lesions during diet therapy may be reversible and
      independent of the ketogenic diet. CONCLUSIONS: This is the first report of
      reversible white matter lesions during ketogenic diet therapy in glucose
      transporter type 1 deficiency syndrome.

PMID- 24080274
TI  - Brainstem strokes in children: an 11-year series from a tertiary pediatric
      center.
AB  - METHODS: Potential clinical barriers to making a timely diagnosis of pediatric
      brainstem stroke and pitfalls of noninvasive vascular imaging are presented.
      METHODS: An institutional review board-approved institutional database query from
      2001-2012 yielded 15 patients with brainstem strokes. Medical records were
      reviewed for symptoms, stroke severity using the Pediatric National Institutes of
      Health Stroke Scale, and outcomes using the Pediatric Stroke Outcome Measure.
      Magnetic resonance angiography was compared with digital subtraction angiography.
      RESULTS: There were 10 boys and five girls; 9 months to 17 years of age (mean
      7.83 years). Symptoms were headaches (eight); visual problems (eight), seizure
      like activity (seven), motor deficits (six), and decreased level of consciousness
      in four. Time since last seen well was 12 hours to 5 days. Pediatric National
      Institutes of Health Stroke Scale was 1-34; <10 in eight; 3 in 1, 10-20 in two,
      and >20 in four. Strokes were pontine in 13/15 and involved >50% of the pons in
      six and <50% in seven; 2/15 had medullary strokes. Magnetic resonance angiography
      showed basilar artery occlusion in 8/13 patients and vertebral artery dissection
      in two. Digital subtraction angiography done within 9-36 hours of magnetic
      resonance angiography in 10/15 patients confirmed the basilar artery occlusion
      seen by magnetic resonance angiography and showed vertebral artery dissection in
      four patients. Patients were systemically anticoagulated without hemorrhagic
      complications. One patient died. Pediatric Stroke Outcome Measures at 2-36 months
      is 0-5.0/10 (mean 1.25). CONCLUSIONS: Vague symptoms contributed to delays in
      diagnosis. Magnetic resonance angiography was equivalent to digital subtraction
      angiography for basilar artery occlusion but not for vertebral artery dissection.
      Even with basilar artery occlusion and high stroke scales, outcome was good when
      systemic anticoagulation was started promptly.

PMID- 24080275
TI  - The fourth "A" of the "4A" syndrome.

PMID- 24080276
TI  - A role for the CXCR3/CXCL10 axis in Rasmussen encephalitis.
AB  - BACKGROUND: Rasmussen encephalitis is a devastating pediatric syndrome of unknown
      etiology that is characterized by progressive loss of neurological function and
      intractable focal epilepsy. Cytotoxic T lymphocytes have an active role in the
      pathogenic process of Rasmussen encephalitis. We studied the implication of
      CXCL10-CXCR3, a chemotactic axis involved in the pathogenesis of several cases of
      immune encephalitis. METHODS: We analyzed surgical specimens of children with
      Rasmussen encephalitis, and performed functional in vitro assays to test the
      implications of the pathological findings. RESULTS: We found that cytotoxic T
      lymphocytes infiltrating the damaged areas of primary biopsies expressed CXCR3,
      whereas neurons and astrocytes in the same areas expressed CXCL10. The in vitro
      assays demonstrated we found that astrocytes upregulated the expression of CXCL10
      messenger RNA and the release of CXCL10 to the supernatants on stimulation with
      polyinosinic-polycyticylic acid, a synthetic double-stranded RNA that mimics
      infections with either RNA or DNA viruses. Activated T lymphocytes responded to
      the production of CXCL10 by astrocytes by increasing their migration in a
      transwell assay. Finally, the chemotaxis induced by the stimulated astrocytes was
      completely abrogated in the presence of a small molecule antagonist of CXCR3.
      CONCLUSIONS: Our results suggest that the CXCR3-CXCL10 axis has a role in
      recruiting pathogenic T lymphocytes into the brains of patients with Rasmussen
      encephalitis. This chemotactic mechanism may be targeted pharmacologically.

PMID- 24080277
TI  - Brain arteriovenous malformations in patients with hereditary hemorrhagic
      telangiectasia: clinical presentation and anatomical distribution.
AB  - BACKGROUND: Hereditary hemorrhagic telangiectasia is an autosomal dominant
      genetic disease with a wide array of vascular malformations involving multiple
      organs. Brain arteriovenous malformations can lead to intracranial hemorrhage and
      are often diagnosed only after patients become symptomatic. Early diagnosis and
      interventional treatment may prevent neurologic sequelae or death. Because of the
      rarity of defined cases, the spectrum of presentations in children with brain
      arteriovenous malformations and hereditary hemorrhagic telangiectasia has not
      been explored in detail. Here, we report our experience in children with
      hereditary hemorrhagic telangiectasia and brain arteriovenous malformations
      regarding both disease manifestations at presentation and the spectrum of brain
      arteriovenous malformation manifestations. METHODS: A retrospective review of
      demographics, clinical manifestations, and brain magnetic resonance
      imaging/computed tomography scan findings in 115 patients with confirmed
      hereditary hemorrhagic telangiectasia (HHT) was conducted using the Hospital for
      Sick Children's HHT Clinic database for the years 1997-2012. RESULTS: Eleven
      patients (four girls and seven boys) were diagnosed with hereditary hemorrhagic
      telangiectasia and brain arteriovenous malformations during this period. Five
      patients initially presented with epistaxis, four presented with intracranial
      hemorrhage, and two were asymptomatic with a positive family history of confirmed
      hereditary hemorrhagic telangiectasia. Although all children had an index case
      with hereditary hemorrhagic telangiectasia in the family, in three patients,
      hereditary hemorrhagic telangiectasia was not diagnosed before the child's
      presentation with intracranial hemorrhage. Multiple brain arteriovenous
      malformations were found in five patients, with one patient having bithalamic
      arteriovenous malformations. CONCLUSIONS: This study highlights the importance of
      both family history and early clinical signs to prompt further diagnostic testing
      to avoid intracranial hemorrhage from brain arteriovenous malformations in
      children with hereditary hemorrhagic telangiectasia.

PMID- 24080278
TI  - Cytoplasmic irradiation results in mitochondrial dysfunction and DRP1-dependent
      mitochondrial fission.
AB  - Direct DNA damage is often considered the primary cause of cancer in patients
      exposed to ionizing radiation or environmental carcinogens. Although mitochondria
      are known to play an important role in radiation-induced cellular response, the
      mechanisms by which cytoplasmic stimuli modulate mitochondrial dynamics and
      functions are largely unknown. In the present study, we examined changes in
      mitochondrial dynamics and functions triggered by alpha particle damage to the
      mitochondria in human small airway epithelial cells, using a precision microbeam
      irradiator with a beam width of 1 MUm. Targeted cytoplasmic irradiation using
      this device resulted in mitochondrial fragmentation and a reduction of cytochrome
      c oxidase and succinate dehydrogenase activity, when compared with nonirradiated
      controls, suggesting a reduction in respiratory chain function. In addition,
      mitochondrial fragmentation or fission was associated with increased expression
      of the dynamin-like protein DRP1, which promotes mitochondrial fission. DRP1
      inhibition by the drug mdivi-1 prevented radiation-induced mitochondrial fission,
      but respiratory chain function in mitochondria inhibited by radiation persisted
      for 12 hours. Irradiated cells also showed an increase in mitochondria-derived
      superoxide that could be quenched by dimethyl sulfoxide. Taken together, our
      results provide a mechanistic explanation for the extranuclear, nontargeted
      effects of ionizing radiation.

PMID- 24080279
TI  - Senescent fibroblasts in melanoma initiation and progression: an integrated
      theoretical, experimental, and clinical approach.
AB  - We present an integrated study to understand the key role of senescent
      fibroblasts in driving melanoma progression. Based on the hybrid cellular
      automata paradigm, we developed an in silico model of normal skin. The model
      focuses on key cellular and microenvironmental variables that regulate
      interactions among keratinocytes, melanocytes, and fibroblasts, key components of
      the skin. The model recapitulates normal skin structure and is robust enough to
      withstand physical as well as biochemical perturbations. Furthermore, the model
      predicted the important role of the skin microenvironment in melanoma initiation
      and progression. Our in vitro experiments showed that dermal fibroblasts, which
      are an important source of growth factors in the skin, adopt a secretory
      phenotype that facilitates cancer cell growth and invasion when they become
      senescent. Our coculture experiments showed that the senescent fibroblasts
      promoted the growth of nontumorigenic melanoma cells and enhanced the invasion of
      advanced melanoma cells. Motivated by these experimental results, we incorporated
      senescent fibroblasts into our model and showed that senescent fibroblasts
      transform the skin microenvironment and subsequently change the skin architecture
      by enhancing the growth and invasion of normal melanocytes. The interaction
      between senescent fibroblasts and the early-stage melanoma cells leads to
      melanoma initiation and progression. Of microenvironmental factors that senescent
      fibroblasts produce, proteases are shown to be one of the key contributing
      factors that promoted melanoma development from our simulations. Although not a
      direct validation, we also observed increased proteolytic activity in stromal
      fields adjacent to melanoma lesions in human histology. This leads us to the
      conclusion that senescent fibroblasts may create a prooncogenic skin
      microenvironment that cooperates with mutant melanocytes to drive melanoma
      initiation and progression and should therefore be considered as a potential
      future therapeutic target. Interestingly, our simulations to test the effects of
      a stroma-targeting therapy that negates the influence of proteolytic activity
      showed that the treatment could be effective in delaying melanoma initiation and
      progression.

PMID- 24080280
TI  - Free somatostatin receptor fraction predicts the antiproliferative effect of
      octreotide in a neuroendocrine tumor model: implications for dose optimization.
AB  - Somatostatin receptors (SSTR) are highly expressed in well-differentiated
      neuroendocrine tumors (NET). Octreotide, an SSTR agonist, has been used to
      suppress the production of vasoactive hormones and relieve symptoms of hormone
      hypersecretion with functional NETs. In a clinical trial, an empiric dose of
      octreotide treatment prolonged time to tumor progression in patients with small
      bowel neuroendocrine (carcinoid) tumors, irrespective of symptom status. However,
      there has yet to be a dose optimization study across the patient population, and
      methods are currently lacking to optimize dosing of octreotide therapy on an
      individual basis. Multiple factors such as total tumor burden, receptor
      expression levels, and nontarget organ metabolism/excretion may contribute to a
      variation in SSTR octreotide occupancy with a given dose among different
      patients. In this study, we report the development of an imaging method to
      measure surface SSTR expression and occupancy level using the PET radiotracer
      (68)Ga-DOTATOC. In an animal model, SSTR occupancy by octreotide was assessed
      quantitatively with (68)Ga-DOTATOC PET, with the finding that increased occupancy
      resulted in decreased tumor proliferation rate. The results suggested that
      quantitative SSTR imaging during octreotide therapy has the potential to
      determine the fractional receptor occupancy in NETs, thereby allowing octreotide
      dosing to be optimized readily in individual patients. Clinical trials validating
      this approach are warranted.

PMID- 24080281
TI  - Intimointimal intussusception in both the proximal and distal ascending aorta: a
      rare clinical form of acute type A aortic dissection.

PMID- 24080282
TI  - The N2 paradox: similar outcomes of pre- and postoperatively identified single
      zone N2a positive non-small-cell lung cancer.
AB  - OBJECTIVES: Resection of N2a non-small-cell lung cancer (NSCLC) diagnosed
      preoperatively is controversial but there is support for resection of unexpected
      N2 disease discovered at surgery. Since the seventh TNM edition, we have
      intentionally resected clinical N2a disease. To validate this policy, we
      determined prognostic factors associated with all resected N2 disease. METHODS:
      From a prospective database of 1131 consecutive patients undergoing elective
      resection for primary lung cancer over a period of 8 years, we identified 68
      patients (35 females (51.4%), mean age 66 years, standard deviation (SD) 9 years)
      who had pathological N2 disease. All patients had positron emission computed
      tomography (CT-PET) staging and selective mediastinoscopy. A Cox-regression
      analysis was performed to identify prognostic factors. RESULTS: At a median
      follow-up of 38.7 months (standard error 10, 95% confidence interval (CI) 19.0
      58.4), the overall median survival was 22.2 months (95% CI 14.6-29.8) with 1-, 2-
      and 5-year survival rates of 63.3, 46.6 and 13.2%, respectively. Survival after
      resection of pN2 disease is adversely affected by the need for pneumonectomy,
      multizone pN2b involvement and by non-compliance with adjuvant chemotherapy.
      Pathological involvement of the subcarinal zone but no other zone appears to be
      associated with an adverse prognosis (hazard ratio (HR) 1.87, P = 0.063).
      Importantly, long-term survival is not different between those patients who have
      a negative preoperative PET-CT scan and yet are found to have pN2 after
      resection, and those who are single-zone cN2a positive before resection on PET-CT
      scan (HR 1.37, P = 0.335). CONCLUSIONS: Our results support a policy of
      intentionally resecting single-zone N2a NSCLC identified preoperatively as part
      of a multimodality therapy.

PMID- 24080283
TI  - Pseudomembranous collagenous colitis with superimposed drug damage.
AB  - Pseudomembranous collagenous colitis is a rare pathological condition, not
      related to infectious agents, and characterized by thickening of the
      subepithelial collagen and formation of pseudomembranes. We report one such case,
      which responded to budesonide treatment after failures of previous approaches
      given, being unaware of the correct diagnosis. 

PMID- 24080284
TI  - Potential role of plasmacytoid dendritic cells for FOXP3+ regulatory T cell
      development in human colorectal cancer and tumor draining lymph node.
AB  - FOXP3(+) regulatory T cells (Tregs) play an important role in the maintenance of
      tumor immunity tolerance. Compared with conventional myeloid dentritic cells
      (mDCs), plasmacytoid dendritic cells (pDCs) exhibit poor immunostimulatory
      ability, and their interaction with T cells often promotes the development of
      Tregs. The aim of this study was to determine FOXP3(+) Tregs and CD123(+)pDCs
      infiltration in colorectal cancer and tumor draining lymph node (TDLN), and to
      evaluate the clinical significance and relationship between pDCs infiltration and
      Tregs development in the CRC tolerogenic milieu. An immunohistochemical assay was
      conducted to assess FOXP3(+)Tregs and CD123(+)pDCs infiltration in tumor tissue
      and in metastatic-free TDLN (mfTDLN) and metastatic TDLN (mTDLN). The results
      showed that FOXP3(+) Tregs infiltration was more frequent in tumor tissue than in
      adjacent normal mucosa (P<0.001). FOXP3(+)Tregs infiltration was associated with
      advanced TNM stage and lymph node metastasis (P<0.01 and P<0.01 for TNM stage and
      lymph node metastasis, respectively). Different from FOXP3(+)Tregs, CD123(+)pDCs
      frequencies were lower in most CRC tumor tissues, whereas the positive rate of
      CD123 expression in CRC was significantly higher than in adjacent normal mucosa
      tissue (P<0.01). Compared to mfTDLN, mTDLN was significantly enriched in FOXP3(+)
      Tregs (P<0.01) and increased in pDC/mDC ratio (P<0.01). The statistical analysis
      demonstrated a significant correlation in both Tregs and pDC/mDC ratio in mTDLN.
      These results suggest that there are more FOXP3(+) Tregs with a stronger
      prognostic significance which might promote tumor tolerance, and that
      CD123(+)pDCs might contribute to Tregs development in the CRC tolerogenic milieu.

PMID- 24080285
TI  - Instruments for measuring mental health recovery: a systematic review.
AB  - Persons in recovery, providers, and policymakers alike are advocating for
      recovery-oriented mental health care, with the promotion of recovery becoming a
      prominent feature of mental health policy in the United States and
      internationally. One step toward creating a recovery-oriented system of care is
      to use recovery-oriented outcome measures. Numerous instruments have been
      developed to assess progress towards mental health recovery. This review
      identifies instruments of mental health recovery and evaluates the
      appropriateness of their use including their psychometric properties, ease of
      administration, and service-user involvement in their development. A literature
      search using the Medline and Psych-INFO databases was conducted, identifying 21
      instruments for potential inclusion in this review, of which thirteen met
      inclusion criteria. Results suggest only three instruments (25%) have had their
      psychometric properties assessed in three or more unique samples of participants.
      Ease of administration varied between instruments, and for the majority of
      instruments, development included service user involvement. This review updates
      and expands previous reviews of instruments to assess mental health recovery. As
      mental health care continues to transform to a recovery-oriented model of service
      delivery, this review may facilitate selection of appropriate assessments of
      mental health recovery for systems to use in evaluating and improving the care
      they provide. 

PMID- 24080286
TI  - Generation of induced pluripotent stem cells with high efficiency from human
      umbilical cord blood mononuclear cells.
AB  - Human induced pluripotent stem cells (iPSCs) hold great promise for regenerative
      medicine. Generating iPSCs from immunologically immature newborn umbilical cord
      blood mononuclear cells (UCBMCs) is of great significance. Here we report
      generation of human iPSCs with great efficiency from UCBMCs using a dox-inducible
      lentiviral system carrying four Yamanaka factors. We generated these cells by
      optimizing the existing iPSC induction protocol. The UCBMC-derived iPSCs (UCB
      iPSCs) have characteristics that are identical to pluripotent human embryonic
      stem cells (hESCs). This study highlights the use of UCBMCs to generate highly
      functional human iPSCs that could accelerate the development of cell-based
      regenerative therapy for patients suffering from various diseases. 

PMID- 24080287
TI  - Neuromuscular strategies for lumbopelvic control during frontal and sagittal
      plane movement challenges differ between people with and without low back pain.
AB  - Observation-based assessments of movement are a standard component in clinical
      assessment of patients with non-specific low back pain. While aberrant motion
      patterns can be detected visually, clinicians are unable to assess underlying
      neuromuscular strategies during these tests. The purpose of this study was to
      compare coordination of the trunk and hip muscles during 2 commonly used
      assessments for lumbopelvic control in people with low back pain (LBP) and
      matched control subjects. Electromyography was recorded from hip and trunk
      muscles of 34 participants (17 with LBP) during performance of the Active Hip
      Abduction (AHAbd) and Active Straight Leg Raise (ASLR) tests. Relative muscle
      timing was calculated using cross-correlation. Participants with LBP demonstrated
      a variable strategy, while control subjects used a consistent proximal to distal
      activation strategy during both frontal and sagittal plane movements. Findings
      from this study provide insight into underlying neuromuscular control during
      commonly used assessment tests for patients with LBP that may help to guide
      targeted intervention approaches. 

PMID- 24080288
TI  - High pressure assist-alkali pretreatment of cotton stalk and physiochemical
      characterization of biomass.
AB  - Ground cotton stalks were pretreated with sodium hydroxide (NaOH) at
      concentrations of 1-4% (w/v), pressures of 30-130 kPa, durations of 15-75 min,
      and liquid/solid ratios of 10:1-30:1. Modeling of the high pressure assist-alkali
      pretreatment (HPAP) of cotton stalk was attempted. The levels of NaOH
      concentration, pressure, and duration were optimized using a Box-Behnken design
      to enhance the cellulose content of treated solid residue. The optimum
      pretreatment conditions were as follows: liquid/solid ratio, 20:1; pressure, 130
      kPa; NaOH concentration, 3.0%; duration, 40 min. During the conditions, cellulose
      content of pretreated cotton stalk residue was 64.07%. The maximum cellulose
      conversion of 45.82% and reducing sugar yield of 0.293 g/g upon hydrolysis were
      obtained. Significant differences were observed in biomass composition and
      physiochemical characteristics between native and alkali-treated biomass. High
      NaOH concentration and pressure were conducive to lignin dissolution and resulted
      in increased cellulose content and conversion.

PMID- 24080289
TI  - Selective defunctionalization by TiO2 of monomeric phenolics from lignin
      pyrolysis into simple phenols.
AB  - This study is focused on defunctionalizing monomeric phenolics from lignin into
      simple phenols for applications such as phenol/formaldehyde resins, epoxidized
      novolacs, adhesives and binders. Towards this goal, Titanium dioxide (TiO2) was
      used to selectively remove hydroxyl, methoxy, carbonyl and carboxyl
      functionalities from the monomeric phenolic compounds from lignin to produce
      mainly phenol, cresols and xylenols. The results showed that anatase TiO2 was
      more selective and active compared to rutile TiO2. Catechols were found to be the
      most reactive phenolics and 4-ethylguaiacol the least reactive with anatase TiO2.
      An overall conversion of about 87% of the phenolics was achieved at 550 degrees C
      with a catalyst-to-feed ratio of 5 w/w. Over 97% conversion of phenolics is
      achievable at moderate temperatures (550 degrees C or <= 600 degrees C) and a
      moderate catalyst-to-feed ratio of 6.5:1. The reactivity of catechols on TiO2
      suggests that titania is a promising catalyst in the removal of hydroxyl moiety.

PMID- 24080290
TI  - Substrate induced emergence of different active bacterial and archaeal
      assemblages during biomethane production.
AB  - This study analyzed the composition of a methane-generating microbial community
      and the corresponding active members during the transformation of three target
      substrates (food waste, cellulose or xylan) by barcoded 454 pyrosequencing of the
      bacterial and archaeal 16S rRNA genes in the DNA and RNA. The number of
      operational taxonomic units at 97% similarity for bacteria and archaea ranged
      from 162-261 and 31-166, respectively. Principal coordinates analysis and Venn
      diagram revealed that there were significant differences in the microbial
      community structure between the active members transforming each substrate and
      the inoculum. The active bacterial populations detected were those required for
      the hydrolysis of the amended substrate. The active archaeal populations were
      methanogens but the ratio of Methanosarcinales and Methanomicrobiales varied
      between the cultures. Overall, results of this study showed that a subset of the
      populations became active and altered in relative abundance during methane
      production according to the amended substrate. 

PMID- 24080291
TI  - Selection of process alternatives for lignocellulosic bioethanol production using
      a MILP approach.
AB  - This work proposes a decision-making framework for the selection of processes and
      unit operations for lignocellulosic bioethanol production. Process alternatives
      are described by its capital and operating expenditures, its contribution to
      process yield and technological availability information. A case study in second
      generation ethanol production using Eucalyptus globulus as raw material is
      presented to test the developed process synthesis tool. Results indicate that
      production cost does not necessarily decrease when yield increases. Hence,
      optimal processes can be found at the inflexion point of total costs and yield.
      The developed process synthesis tool provides results with an affordable
      computational cost, existing optimization tools and an easy-to-upgrade
      description of the process alternatives. These features made this tool suitable
      for process screening when incomplete information regarding process alternatives
      is available. 

PMID- 24080292
TI  - Constructed wetland as an ecotechnological tool for pollution treatment for
      conservation of Ganga river.
AB  - With aim to develop an efficient and ecofriendly approach for on-site treatment
      of sewage, a sub-surface flow constructed wetland (CW) has been developed by
      raising potential aquatic macrophytes; Typha latifolia, Phragmites australis,
      Colocasia esculenta, Polygonum hydropiper, Alternanthera sessilis and Pistia
      stratoites in gravel as medium. Sewage treatment potential of CW was evaluated by
      varying retention time at three different stages of plant growth and
      stabilization. After 6 months, monitoring of fully established CW indicated
      reduction of 90%, 65%, 78%, 84%, 76% and 86% of BOD, TSS, TDS, NO3-N, PO4-P and
      NH4-N, respectively in comparison to inlet after 36 h of retention time. Sewage
      treatment through CW also resulted in reduction of heavy metal contents. Thus, CW
      proved an effective method for treatment of wastewater and may be developed along
      river Ganga stretch as an alternative technology. Treated water may be drained
      into river to check further deterioration of Ganga water quality.

PMID- 24080293
TI  - Influence of process parameters on the surface and chemical properties of
      activated carbon obtained from biochar by chemical activation.
AB  - Activated carbons were produced from biochar obtained through pyrolysis of
      safflower seed press cake by chemical activation with zinc chloride. The
      influences of process variables such as the activation temperature and the
      impregnation ratio on textural and chemical-surface properties of the activated
      carbons were investigated. Also, the adsorptive properties of activated carbons
      were tested using methylene blue dye as the targeted adsorbate. The experimental
      data indicated that the adsorption isotherms are well described by the Langmuir
      equilibrium isotherm equation. The optimum conditions resulted in activated
      carbon with a monolayer adsorption capacity of 128.21 mg g(-1) and carbon content
      76.29%, while the BET surface area and total pore volume corresponded to
      801.5m(2)g(-1) and 0.393 cm(3)g(-1), respectively. This study demonstrated that
      high surface area activated carbons can be prepared from the chemical activation
      of biochar with zinc chloride as activating agents.

PMID- 24080294
TI  - Development of experimental design approach and ANN-based models for
      determination of Cr(VI) ions uptake rate from aqueous solution onto the solid
      biodiesel waste residue.
AB  - In the present work, the evaluation capacities of two optimization methodologies
      such as RSM and ANN were employed and compared for predication of Cr(VI) uptake
      rate using defatted pongamia oil cake (DPOC) in both batch and column mode. The
      influence of operating parameters was investigated through a central composite
      design (CCD) of RSM using Design Expert 8.0.7.1 software. The same data was fed
      as input in ANN to obtain a trained the multilayer feed-forward networks back
      propagation algorithm using MATLAB. The performance of the developed ANN models
      were compared with RSM mathematical models for Cr(VI) uptake rate in terms of the
      coefficient of determination (R(2)), root mean square error (RMSE) and absolute
      average deviation (AAD). The estimated values confirm that ANN predominates RSM
      representing the superiority of a trained ANN models over RSM models in order to
      capture the non-linear behavior of the given system. 

PMID- 24080295
TI  - Co-digestion to support low temperature anaerobic pretreatment of municipal
      sewage in a UASB-digester.
AB  - The aim of this work was to demonstrate that co-digestion improves soluble sewage
      COD removal efficiency in treatment of low temperature municipal sewage by a UASB
      digester system. A pilot scale UASB-digester system was applied to treat real
      municipal sewage, and glucose was chosen as a model co-substrate. Co-substrate
      was added in the sludge digester to produce additional methanogenic biomass,
      which was continuously recycled to inoculate the UASB reactor. Soluble sewage COD
      removal efficiency increased from 6 to 23%, which was similar to its biological
      methane potential (BMP). Specific methanogenic activity of the UASB and of the
      digester sludge at 15 degrees C tripled to a value respectively of 43 and 39 mg
      CH4-COD/(g VSS d). Methane production in the UASB reactor increased by more than
      90% due to its doubled methanogenic capacity. Therefore, co-digestion is a
      suitable approach to support a UASB-digester for pretreatment of low temperature
      municipal sewage.

PMID- 24080296
TI  - Probing electron transfer with Escherichia coli: a method to examine
      exoelectronics in microbial fuel cell type systems.
AB  - Escherichia coli require mediators or composite anodes for substantial outward
      electron transfer, >8A/m(2). To what extent non-mediated direct electron transfer
      from the outer cell envelope to the anode occurs with E. coli is a debated issue.
      To this end, the redox behaviour of non-exoelectrogenic E. coli K12 was
      investigated using a bi-cathodic microbial fuel cell. The electromotive force
      caused by E. coli biofilms mounted 0.2-0.3 V above the value with the surrounding
      medium. Surprisingly, biofilms that started forming at different times
      synchronised their EMF even when physically separated. Non-mediated electron
      transfer from E. coli biofilms increased above background currents passing
      through the cultivation medium. In some instances, currents were rather high
      because of a sudden discharge of the medium constituents. Mediated conditions
      provided similar but more pronounced effects. The combined step-by-step method
      used allowed a systematic analysis of exoelectronics as encountered in microbial
      fuel cells.

PMID- 24080297
TI  - Imaging the in vivo fate of human T cells following transplantation in
      immunoincompetent mice - implications for clinical cell therapy trials.
AB  - Many forms of adoptive T cell therapy are on the verge of being translated to the
      clinic. To gain further insight in their immunomodulating functions and to
      optimize future clinical trials it is essential to develop techniques to study
      their homing capacity. CD4+ T cells were labeled using [(111)In]oxine, and the
      radioactive uptake was determined in vitro before intravenous injection in
      immunodeficient mice. In vivo biodistribution of [(111)In]oxine-labeled cells or
      tracer alone was subsequently measured by MUSPECT/CT and organ distribution. CD4+
      T cells incorporated [(111)In]oxine with higher labeling yield using Ringer
      Acetate compared to 0.9% NaCl. Cellular viability after labeling with
      [(111)In]oxine was not compromised using less than 0.4 MBq/million cells. After
      intravenous infusion CD4+ T cells preferentially homed to the liver (p<0.01) and
      spleen (p<0.05). This study presents a protocol for labeling of T cells by
      [(111)In]oxine with preserved viability and in vivo tracking by SPECT for up to
      8days, which can easily be translated to clinical cell therapy trials.

PMID- 24080298
TI  - Dosimetric comparison of multichannel with one single-channel vaginal cylinder
      for vaginal cancer treatments with high-dose-rate brachytherapy.
AB  - PURPOSE: To compare the three-dimensional (3D) image (CT/MR)-based planning with
      a multichannel vaginal cylinder (MVC) to a single-channel vaginal cylinder (SVC)
      for the treatment of vaginal cancer. METHODS AND MATERIALS: A total of 20
      consecutive patients were treated with 3D CT/MR image-based high-dose-rate (HDR)
      brachytherapy using an MVC. All patients received external beam radiation therapy
      before HDR brachytherapy. A brachytherapy dose of 20-25Gy of more than five
      fractions was delivered to clinical target volume (CTV). Retrospectively,
      treatment plans for all patients were generated using the central channel only to
      mimic an SVC applicator. The SVC plans were optimized to match CTV coverage with
      MVC plans. Dose homogeneity index as well as bladder, rectum, sigmoid, and
      urethral doses were compared. RESULTS: The mean D90 for CTV was 74.2Gy (range:
      48.8-84.1Gy). The mean (+/-standard deviation) of dose homogeneity index for MVC
      vs. SVC was 0.49 (+/-0.19) and 0.52 (+/-0.23), respectively (p=0.09). Mean
      bladder 0.1, 1, and 2cc doses for MVC vs. SVC were 69 vs. 71.2Gy (p=0.35), 61.4
      vs. 63.8Gy (p=0.1), and 59.5 vs. 60.9Gy (p=0.31), respectively. Similarly, mean
      rectum 0.1, 1, and 2cc doses for MVC vs. SVC were 67.2 vs. 75.4Gy (p=0.005), 60.0
      vs. 65.6Gy (p=0.008), and 57.3 vs. 62.0Gy (p=0.015), respectively, and mean
      sigmoid doses were 56.3 vs. 60.5Gy (p=0.10), 50.9 vs. 53.1Gy (p=0.09), and 49.1
      vs. 50.7Gy (p=0.10), respectively. CONCLUSION: The 3D CT-/MR-based plan with MVC
      may provide better dose distribution in the management of certain clinical
      situations of vaginal cancer requiring intracavitary brachytherapy, especially in
      minimizing potential late rectal complications.

PMID- 24080299
TI  - Validation study of ultrasound-based high-dose-rate prostate brachytherapy
      planning compared with CT-based planning.
AB  - PURPOSE: The use of transrectal ultrasound (TRUS) to both guide and plan high
      dose-rate (HDR) brachytherapy (BT) for prostate is increasing. Studies using
      prostate phantoms have demonstrated the accuracy of ultrasound (US) needle tip
      reconstruction compared with CT imaging standard. We have assessed the in vivo
      accuracy of needle tip localization by TRUS using cone-beam CT (CBCT) as our
      reference standard. METHODS AND MATERIALS: Needle positions from 37 implants have
      been analyzed. A median of 16 needles (range, 16-18) per implant were inserted,
      advanced to the prostate base, and their tips identified using live TRUS images
      and real-time planning BT software. Needle protrusion length from the template
      was recorded to allow for reverification before capturing images for planning.
      The needles remained locked in the template, which was fixed to the stepper,
      while a set of three-dimensional TRUS images was acquired for needle path
      reconstruction and HDR-BT treatment planning. Following treatment, CBCT images
      were acquired for subsequent needle reconstruction using a BT Treatment Planning
      System. The coordinates of each needle tip were recorded from the Treatment
      Planning System for CT and US and compared. RESULTS: A total of 574 needle tip
      positions have been compared between TRUS and CBCT. Of these, 59% agreed within 1
      mm, 27% within 1-2 mm, and 11% agreed within 2-3 mm. The discrepancy between tip
      positions in the two modalities was greater than 3 mm for only 20 needles (3%).
      CONCLUSIONS: The US needle tip identification in vivo is at least as accurate as
      CT identification, while providing all the advantages of a one-step procedure.

PMID- 24080300
TI  - Prevalence of symptoms consistent with a diagnosis of vulvodynia: population
      based estimates from 2 geographic regions.
AB  - OBJECTIVE: We used validated sensitive and specific questions associated with
      clinically confirmed diagnoses of unexplained vulvar pain (vulvodynia) to compare
      the cumulative incidence of vulvar pain and prevalence of care-seeking behavior
      in Boston metropolitan area (BMA) and in Minneapolis/Saint Paul metropolitan area
      (MSP) from 2001 through 2005 using census-based data, and 2010 through 2012,
      using outpatient community-clinic data, respectively. STUDY DESIGN: We received
      self-administered questionnaires from 5440 women in BMA and 13,681 in MSP, 18-40
      years of age, describing their history of vulvar burning or pain on contact that
      persisted >3 months that limited/prevented intercourse. RESULTS: By age 40 years,
      7-8% in BMA and MSP reported vulvar pain consistent with vulvodynia. Women of
      Hispanic origin compared to whites were 1.4 times more likely to develop vulvar
      pain symptoms (95% confidence interval, 1.1-1.8). Many women in MSP (48%) and BMA
      (30%) never sought treatment, and >50% who sought care with known health care
      access received no diagnosis. CONCLUSION: Using identical screening methods, we
      report high prevalence of vulvar pain in 2 geographic regions, and that access to
      health care does not increase the likelihood of seeking care for chronic vulvar
      pain.

PMID- 24080301
TI  - Reply: To PMID 23659985.

PMID- 24080302
TI  - Herpes simplex virus 2-induced activation in vaginal cells involves Toll-like
      receptors 2 and 9 and DNA sensors DAI and IFI16.
AB  - OBJECTIVE: The pathway by which herpes simplex virus 2 (HSV2) triggers the innate
      immune system in the urogenital system has not as yet been fully elucidated. In
      this study, we aimed to determine which pattern recognition receptors (PRRs)
      recognize HSV2 in primary vaginal epithelial cells. Once we deciphered the
      receptors involved, we aimed to target them to immunomodulate innate responses as
      a prophylactic or therapeutic intervention for early HSV2 infection. STUDY
      DESIGN: To determine which PRRs are involved, receptor silencing as well as
      confocal microscopy was utilized. For immunomodulation, PRR agonists were
      utilized to induce a strong, local response to limit the infection, and we used 2
      quantitative methods, flow cytometry and plaque assays, to determine their effect
      on HSV2 replication. RESULTS: Our results show that HSV2 is detected by a
      plethora of PRRs: Toll-like receptors (TLR) 2 as well as deoxyribonucleic acid
      (DNA) sensors TLR9, DNA-dependent activator of interferon regulatory factors, and
      to a lesser extent interferon-inducible 16, which trigger cytokine secretion to
      protect the host. Using PRR agonists, such as lipoproteins, CpG DNA, and cyclic
      dinucleotides, we could significantly limit HSV2 replication. CONCLUSION:
      Different PRRs are strategically placed in different cell locations to detect
      virus invasion. Use of agonists that target and activate these PRRs appeared to
      be effective in preventing primary HSV2 infection in vaginal cells and could
      provide new insights in defense against HSV2 urogenital infections.

PMID- 24080303
TI  - Maternal metformin, obesity, and metabolic syndrome: the contribution of
      autonomic nervous system function.

PMID- 24080304
TI  - Submucosal fibroids and the relation to heavy menstrual bleeding and anemia.
AB  - OBJECTIVE: The objective of the study was to determine the contribution of
      submucosal fibroids (SMs) to heavy menstrual bleeding (HMB) and anemia among
      women with HMB. STUDY DESIGN: Our retrospective study included premenopausal
      women who presented to a tertiary care center for HMB between January 2007 and
      October 2011. All women in this cohort underwent flexible office hysteroscopy (n
      = 1665) and 259 (15.6%) had SMs. We also reviewed the clinical ultrasounds (n =
      914) from these women to determine whether SMs (n = 148) or any fibroids (n =
      434) were present in the uterus. Clinical evaluation of bleeding included
      hemoglobin and pictorial blood loss assessment charts. RESULTS: In our cohort,
      hysteroscopically diagnosed SMs were associated with significantly lower
      hemoglobin (adjusted difference -0.35 g/dL; 95% confidence interval [CI], -0.56
      g/dL to -0.13g/dL) and higher risk of anemia (odds ratio [OR], 1.46; 95% CI, 1.04
      2.03). Women with ultrasound-diagnosed SMs had lower hemoglobin and anemia, but
      results were not significant once adjusted for confounders (hemoglobin: adjusted
      difference -0.21 g/dL; 95% CI, -0.47g/dL to 0.06 g/dL; and anemia: OR, 1.28; 95%
      CI, 0.82-1.97). Ultrasound-diagnosed fibroids anywhere in the uterus were not
      associated with hemoglobin (P = .7) or anemia (P = .8). Self-reported pictorial
      blood loss assessment charts scores did not differ between women with and without
      fibroids diagnosed by either hysteroscopy or ultrasound (P = .4 and P = .9,
      respectively). CONCLUSION: SMs were related to lower hemoglobin and higher risk
      of anemia but not self-reported bleeding scores. Diagnostic modality was
      important: hysteroscopically diagnosed SMs had lower hemoglobin and more anemia
      than ultrasound-diagnosed SMs. This may explain the inconsistent results in the
      literature.

PMID- 24080305
TI  - The relationship of hypovitaminosis D and IL-6 in preeclampsia.
AB  - OBJECTIVE: Vitamin D deficiency has been linked to the pathogenesis of
      preeclampsia. Given the demonstrated antiinflammatory function of vitamin D in
      multiple organ systems including trophoblast cells and placenta, we hypothesized
      that vitamin D deficiency contributes to the development of preeclampsia through
      increased inflammation, as indicated by elevated interleukin (IL)-6
      concentrations. STUDY DESIGN: Plasma samples from a large preeclampsia cohort
      study were examined in 100 preeclamptic and 100 normotensive pregnant women.
      Comparisons of vitamin D and IL-6 concentrations used Student t test and chi(2)
      test or their nonparametric counterparts. A logistic regression model assessed
      the association among vitamin D, IL-6 concentrations, and preeclampsia risk.
      RESULTS: The mean concentration of 25-hydroxyvitamin D was 49.4 +/- 22.6 nmol/L
      in normotensives and 42.3 +/- 17.3 nmol/L in preeclamptic women (P = .01). The
      median (interquartile range: Q1, Q3) concentrations of IL-6 were 2.0 (1.3, 3.4)
      pg/mL and 4.4 (2.2, 10.0) pg/mL in the control and preeclampsia groups,
      respectively (P < .01). We observed a significant association between IL-6
      elevation and preeclampsia (odds ratio, 4.4; 95% confidence interval, 1.8-10.8; P
      < .01) and between vitamin D deficiency and preeclampsia (odds ratio, 4.2; 95%
      confidence interval, 1.4-12.8; P = .04). However, there was no association
      between vitamin D deficiency and IL-6 elevation. CONCLUSION: Third-trimester IL-6
      elevation and vitamin D deficiency were independently associated with the risk of
      preeclampsia. We found no evidence to support the hypothesis that vitamin D
      deficiency alters the pathogenesis of preeclampsia by activation of inflammation
      as assessed by IL-6 concentration.

PMID- 24080306
TI  - Genetic analysis of the fused in sarcoma gene in Chinese Han patients with
      Parkinson's disease.
AB  - BACKGROUND AND PURPOSE: Exome sequencing in a large essential tremor (ET) family
      identified a novel nonsense mutation (p.Q290X) in the fused in sarcoma gene (FUS)
      as the cause of this family. Because of the clinical overlap between ET and
      Parkinson's disease (PD), the role of FUS in an independent cohort of PD patients
      from China mainland was evaluated. METHODS: The entire coding region of FUS in
      508 Chinese Han patients with PD and the identified variants in 633 normal
      controls were evaluated. A variant was further screened in an additional 382
      controls for the frequency in our population. RESULTS: A novel variant c.696C > T
      (p.Y232Y) in 2 sporadic patients with PD and six variants (c.52C > A, p.P18T;
      c.52C > T, p.P18S; c.147C > A, p.G49G; c.291C > T, p.Y97Y; c.684C > T, p.G228G;
      c.1176G > A, p.M392I) without significant difference in genotypic and allelic
      distributions in our PD cohort were identified. CONCLUSION: The FUS gene is not a
      genetic risk factor for PD in the population of Chinese Han ethnicity.

PMID- 24080307
TI  - Do non-motor symptoms in Parkinson's disease differ from essential tremor before
      initial diagnosis? A clinical and scintigraphic study.
AB  - BACKGROUND: Non-motor symptoms (NMS) in Parkinson's disease (PD) are common,
      increase the patients' disability and have a significantly negative impact on
      their quality of life. Essential tremor (ET) is also affected by non-motor
      symptoms and often enters into the differential diagnosis with PD. Brain
      scintigraphy with [(123)I]beta-CIT SPECT is a technique used to facilitate
      differential diagnosis between PD and ET. METHODS: We evaluated both motor
      impairment (MDS-UPDRS-III) and non-motor symptoms (NMSQuest) in patients who
      underwent a [(123)I]beta-CIT SPECT examination for diagnostic purposes. Both the
      clinical and the scintigraphic data obtained from the selected PD (n = 31) and ET
      (n = 22) patients were compared. RESULTS: We did not detect a significant
      difference in the total number of NMS reported by either PD (10.4 +/- 4.9) or ET
      patients (8.41 +/- 3.3). PD patients reported more drooling (29%), hyposmia
      (32.2%), hallucinations (19.3%), difficulty in concentrating (51.6%), orthostatic
      dizziness (67.7%), falling (19.3%), vivid dreams (32.2%), REM sleep behavior
      disorder (58%), and diplopia (22.5%) compared with ET patients. PD patients who
      complained of drooling, orthostatic dizziness, and diplopia had greater
      denervation of the caudata than did the PD patients who did not report the same
      symptoms. The differences observed were not associated with differences in age,
      sex, UPDRS-III score, and the presence/absence of tremor. CONCLUSIONS: The
      declaration of non-motor symptoms is influenced by subjective factors that are
      widely suggestible. When analyzed early and before receiving a definitive
      diagnosis, PD patients complain of specific symptoms that seem to depend on
      different pathogenetic mechanisms.

PMID- 24080308
TI  - Communication problems of Parkinson patients using sign language as their main
      communication method.

PMID- 24080309
TI  - Elevated and dysregulated bone morphogenic proteins in immune cells of patients
      with relapsing-remitting multiple sclerosis.
AB  - The abundance of neural stem cells (NSCs) in multiple sclerosis (MS) lesions with
      extensive astrogliosis suggests that fate factors of NSCs, such as the bone
      morphogenic protein (BMP) signaling maybe defective in MS. We found an elevated
      mRNA expression and protein secretion of BMP-2,4,5 but not of BMP-7. This was
      primarily in T cells. Cell stimulation with anti-CD3/CD28 antibodies or with IFN
      gamma induced expression of BMP-2,4,5 mRNA in untreated RR-MS patients,
      indicating that proinflammatory processes in MS may play a role in the BMP-2,4,5
      productions in T cells. These results contribute to the understanding of the
      negligible extent of neurogenesis and oligodendrogenesis with extensive
      astrogliogenesis and the failure of adequate tissue repair in MS lesions. 

PMID- 24080310
TI  - Anti-streptococcal, tubulin, and dopamine receptor 2 antibodies in children with
      PANDAS and Tourette syndrome: single-point and longitudinal assessments.
AB  - Single-point-in-time ELISA optical densities for three putative antibodies
      identified in Sydenham's chorea, the streptococcal group A carbohydrate antigen,
      N-acetyl-beta-d-glucosamine, tubulin, and the dopamine 2 receptor, showed no
      differences in children with PANDAS (n=44) or Tourette syndrome (n=40) as
      compared to controls (n=24). Anti-tubulin and D2 receptor antibodies assessed in
      serial samples from 12 PANDAS subjects obtained prior to a documented
      exacerbation, during the exacerbation (with or without a temporally associated
      streptococcal infection), and following the exacerbation, showed no evidence of
      antibody levels correlating with a clinical exacerbation. These data do not
      support hypotheses suggesting an autoimmune hypothesis in either TS or PANDAS. 

PMID- 24080312
TI  - Fixation probability of mobile genetic elements such as plasmids.
AB  - Mobile genetic elements such as plasmids are increasingly becoming thought of as
      evolutionarily important. Being horizontally transmissible is generally assumed
      to be beneficial for a gene. Using several simple modelling approaches we show
      that in fact being horizontally transferable is just as important for fixation as
      being beneficial to the host, in line with other results. We find fixation
      probability is approximately 2(s+beta), where s is the increased (vertical)
      fitness provided by the gene, and beta the rate of horizontal transfer when rare.
      This result comes about because when the gene is rare, almost all individuals in
      the population are possible recipients of horizontal transfer. The ability to
      horizontally transfer could thus cause a deleterious gene to become fixed in a
      population even without hitchhiking. Our findings provide further evidence for
      the importance and ubiquity of mobile genetic elements, particularly in
      microorganisms. 

PMID- 24080311
TI  - Glutamate receptors and the regulation of steroidogenesis in the human adrenal
      gland: the metabotropic pathway.
AB  - BACKGROUND: l-glutamate is a major excitatory neurotransmitter in the mammalian
      brain. Glutamate receptors have been reported in the rat adrenal cortex and in
      human aldosterone-producing adenomas (APA). However, details regarding the
      expression levels and functions of these receptors in human adrenocortical
      tissues remain unknown. METHODS: The mRNA levels of glutamate receptors were
      evaluated by qPCR in: 12 normal adrenal cortex (NAC), 11 APA, and 12 cortisol
      producing adenoma (CPA) tissues. Protein localization was evaluated by
      immunohistochemistry for 15 NAC, 5 idiopathic hyperaldosteronism cases, 15 APA
      and 15 CPA. H295R cells were treated with angiotensin-II or forskolin alone or
      combined with the GRM2/3 agonist LY354740. RESULTS: The level of GRM3 mRNA was
      higher in APA than in CPA (P=0.0086) or NAC (P=0.0022). GRM1, IGLUR2, and IGLUR3
      were also detected in adrenocortical tissues. When added to angiotensin
      II/forskolin treatments, LY354740 decreased aldosterone and cortisol production
      in H295R cells. CONCLUSIONS: GRM3 is considered to regulate steroidogenesis in
      adrenocortical tissues.

PMID- 24080313
TI  - Chemopreventive effect of quercetin, a natural dietary flavonoid on prostate
      cancer in in vivo model.
AB  - BACKGROUND & AIM: Prostate cancer is one of the frequently diagnosed cancers in
      men. Increased Growth factor IGF-1/IGF-1R axis activation mediated by both
      PI3K/Akt or RAF/MEK/ERK system and AR expression remains important in the
      development and progression of prostate cancer. Targeting such system by dietary
      agents quercetin in vivo model could aid its application in both treatment as
      well as prevention of prostate cancer. METHODS: In our study the rats were
      divided into four groups; Group I: control (propylene glycol-vehicle), Group II:
      cancer-induced (MNU and Testosterone treated) rats, Group III: cancer-induced +
      Quercetin (200 mg/kg body wt/orally) and Group IV: Quercetin (200 mg/kg body wt)
      thrice a week. After the treatment period rats were sacrificed and the ventral
      and dorsolateral prostate lobes were dissected. RESULTS: Antioxidant enzymes and
      apoptotic proteins were significantly decreased in cancer-induced animal and upon
      quercetin supplement its level was increased. The IGFIR, AKT, AR, cell
      proliferative and anti-apoptotic proteins were increased in cancer-induced group
      whereas supplement of quercetin decreased its expression. CONCLUSIONS: Quercetin
      down regulates the cell survival, proliferative and anti-apoptotic proteins
      thereby prevents prostate cancer, by acting as a chemopreventive agent in
      preclinical model.

PMID- 24080314
TI  - Adolescent binge drinking and risky health behaviours: findings from northern
      Russia.
AB  - BACKGROUND: Some evidence suggests that in recent years the prevalence of heavy
      drinking has increased among Russian adolescents. However, as yet, little is
      known about either heavy alcohol consumption or its relationship with other
      adolescent health risk behaviours in Russia. The aim of this study therefore was
      to investigate the association between binge drinking and health risk behaviours
      among adolescents in Russia. METHODS: Data were drawn from the Social and Health
      Assessment (SAHA), a survey carried out in Arkhangelsk, Russia in 2003.
      Information was obtained from a representative sample of 2868 adolescents aged 13
      17 regarding the prevalence and frequency of binge drinking (five or more drinks
      in a row in a couple of hours) and different forms of substance use, risky sexual
      behaviour and violent behaviour. Logistic regression analysis was used to examine
      the association between binge drinking and adolescent involvement in various
      health risk behaviours. RESULTS: Adolescent binge drinking was associated with
      the occurrence of every type of health risk behaviour - with the sole exception
      of non-condom use during last sex. In addition, there was a strong association
      between the number of days on which binge drinking occurred and the prevalence of
      many health risk behaviours. CONCLUSIONS: Binge drinking is associated with a
      variety of health risk behaviours among adolescents in Russia. Public health
      interventions such as reducing the affordability and accessibility of alcohol are
      now needed to reduce binge drinking and its harmful effects on adolescent well
      being.

PMID- 24080316
TI  - Morphological zeta-potential variation of nanoporous anodic alumina layers and
      cell adherence.
AB  - Nanoscale surface modification of biomedical implant materials offers enhanced
      biological activity concerning protein adsorption and cell adherence. Nanoporous
      anodic alumina oxide (AAO) layers were prepared by electrochemical oxidation of
      thin Al-seed layers in 0.22 M C2H2O4, applying anodization voltages of 20-60 V.
      The AAO layers are characterized by a mean pore diameter varying from 15 to 40
      nm, a mean pore distance of 40-130 nm, a total porosity of ~ 10% and a thickness
      of 560 +/- 40 nm. Zeta potential and isoelectric point (iep) were derived from
      streaming potential measurements and correlated to the topology variation of the
      nanoporous AAO layers. With decreasing pore diameter a shift of iep from ~ 7.9
      (pore diameter 40 nm) to ~ 6.7 (pore diameter 15 nm) was observed. Plain alumina
      layers, however, possess an iep of ~ 9. Compared to the plain alumina surface an
      enhanced adherence and activity of hFOB cells was observed on the nanoporous AAO
      after 24h culture with a maximum at a pore size of 40 nm. The topology-induced
      change of the electrochemical surface state may have a strong impact on protein
      adsorption as well as on cell adhesion, which offers a high potential for the
      development of bioactive AAO coatings on various biomaterial substrates.

PMID- 24080315
TI  - L-isocorypalmine reduces behavioral sensitization and rewarding effects of
      cocaine in mice by acting on dopamine receptors.
AB  - BACKGROUND: We previously reported isolation of l-isocorypalmine (l-ICP), a mono
      demethylated analog of l-tetrahydropalmatine (l-THP), from the plant Corydalis
      yanhusuo. Here we characterized its in vitro pharmacological properties and
      examined its effects on cocaine-induced behaviors in mice. METHODS: Receptor
      binding, cAMP and [(35)S]GTPgammaS assays were used to examine pharmacological
      actions of l-ICP in vitro. Effects of l-ICP on cocaine-induced locomotor
      hyperactivity and sensitization and conditioned place preference (CPP) in mice
      were investigated. HPLC was employed to analyze metabolites of l-ICP in mouse
      serum. RESULTS: Among more than 40 targets screened, l-ICP and l-THP bound only
      to dopamine (DA) receptors. l-ICP was a high-affinity partial agonist of D1 and
      D5 receptors and a moderate-affinity antagonist of D2, D3 and D4 receptors,
      whereas l-THP bound to only D1 and D5 receptors, with lower affinities than l
      ICP. At 10mg/kg (i.p.), l-ICP inhibited spontaneous locomotor activity for a
      shorter time than l-THP. Pretreatment with l-ICP reduced cocaine-induced
      locomotor hyperactivities. Administration of l-ICP before cocaine once a day for
      5 days reduced cocaine-induced locomotor sensitization on days 5 and 13 after 7
      days of withdrawal. Pretreatment with l-ICP before cocaine daily for 6 days
      blocked cocaine-induced CPP, while l-ICP itself did not cause preference or
      aversion. HPLC analysis showed that l-ICP was the main compound in mouse serum
      following i.p. injection of l-ICP. CONCLUSIONS: l-ICP likely acts as a D1 partial
      agonist and a D2 antagonist to produce its in vivo effects and may be a promising
      agent for treatment of cocaine addiction.

PMID- 24080317
TI  - In vitro characterization of a controlled-release ocular insert for delivery of
      brimonidine tartrate.
AB  - Glaucoma is the second leading cause of blindness in the US. Brimonidine tartrate
      (BT) is a modern anti-glaucoma agent that is currently administered as frequently
      as a thrice-daily topical eye drop medication. Accordingly, compliance with BT
      regimens is low, limiting overall effectiveness. One attempt that has previously
      proved effective in addressing non-adherence is the formation of ocular inserts,
      such as the Ocusert((r)), whose diffusion-based control released an older drug
      (pilocarpine) for a week-long period. Modern controlled drug-release technology
      provides an avenue for extending the release of practically any drug (including
      new drugs such as BT) for as long as 1 month from a singular insert. Currently,
      no controlled-release formulations for BT exist. This work outlines the
      development and characterization of a BT-releasing ocular insert designed from
      poly(lactic co-glycolic) acid/polyethylene glycol (PEG). It was found that a
      formulation containing 15% PEG can be created that produces a linear BT-release
      profile corresponding to BT eye drop delivery estimates. Additionally, these
      inserts were shown, through the use of atomic force microscopy and scanning
      electron microscopy, to have smooth surfaces and physical properties suitable for
      ophthalmic use.

PMID- 24080318
TI  - Simultaneous hydrolysis-esterification of wet microalgal lipid using acid.
AB  - This research demonstrated hydrolysis of wet microalgal lipid and esterification
      of free fatty acid (FFA) using acid in one-step process. The investigation of
      simultaneous hydrolysis-esterification (SHE) of wet microalgal lipid was
      conducted by using L27 orthogonal design and the effects of water content, volume
      of sulphuric acid, volume of methanol, temperature and time on SHE were examined.
      As a result, water content was found to be the most effective factor. The effects
      of various parameters on fatty acid methyl ester (FAME) content and equilibrium
      relation between FAME and FFA were also examined under water content 80%.
      Equimolar amounts of sulphuric acid and hydrochloric acid showed similar results.
      This method has great potential in terms of biodiesel production from microalgae
      since no organic solvents are used. 

PMID- 24080319
TI  - Ketocarotenoid circulation, but not retinal carotenoid accumulation, is linked to
      eye disease status in a wild songbird.
AB  - Pathogenic or parasitic infections pose numerous physiological challenges to
      organisms. Carotenoid pigments have often been used as biomarkers of disease
      state and impact because they integrate multiple aspects of an individual's
      condition and nutritional and health state. Some diseases are known to influence
      carotenoid uptake from food (e.g. coccidiosis) and carotenoid use (e.g. as
      antioxidants/immunostimulants in the body, or for sexually attractive
      coloration), but there is relatively little information in animals about how
      different types of carotenoids from different tissue sources may be affected by
      disease. Here we tracked carotenoid accumulation in two body pools (retina and
      plasma) as a function of disease state in free-ranging house finches (Haemorhous
      mexicanus). House finches in eastern North America can contract mycoplasmal
      conjunctivitis (Mycoplasma gallisepticum, or MG), which can progress from eye
      swelling to eye closure and death. Previous work showed that systemic immune
      challenges in house finches lower carotenoid levels in retina, where they act as
      photoprotectors and visual filters. We assessed carotenoid levels during the molt
      period, a time of year when finches uniquely metabolize ketocarotenoids (e.g. 3
      hydroxy-echinenone) for acquisition of sexually selected red plumage coloration,
      and found that males infected with MG circulated significantly lower levels of 3
      hydroxy-echinenone, but no other plasma carotenoid types, than birds exhibiting
      no MG symptoms. This result uncovers a key biochemical mechanism for the
      documented detrimental effect of MG on plumage redness in H. mexicanus. In
      contrast, we failed to find a relationship between MG infection status and
      retinal carotenoid concentrations. Thus, we reveal differential effects of an
      infectious eye disease on carotenoid types and tissue pools in a wild songbird.
      At least compared to retinal sources (which appear somewhat more temporally
      stable than other body carotenoid pools, even to diseases of the eye evidently),
      our results point to either a high physiological cost of ketocarotenoid synthesis
      (as is argued in models of sexually selected carotenoid coloration) or high
      benefit of using this ketocarotenoid to combat infection.

PMID- 24080320
TI  - Protective effect of chitooligosaccharides against cyclophosphamide-induced
      immunosuppression in mice.
AB  - Chitooligosaccharides (COS) display a variety of important biological activities,
      including antimicrobial, antitumor, anti-inflammatory, and immunoenhancing. In
      the present study, a COS sample (degree of polymerization 4-11, analyzed by FTIR
      and MALDI-TOF-MS) prepared by hydrolysis with a recombinant chitosanase was
      orally administered to mice for evaluation of its effect on cyclophosphamide (Cy)
      induced immunosuppression. Thymus and spleen indices, delayed-type
      hypersensitivity (DTH) reaction, macrophage phagocytosis, and certain enzyme
      activities were significantly higher in mice treated with COS+Cy than in mice
      treated with Cy alone. ELISA experiments showed that COS treatment enhanced
      production of the cytokines IL-2, IL-12, and IFN-gamma but decreased production
      of IL-10 in sera of Cy-treated mice. The well-defined COS product studied
      displayed strong immunoenhancing activity and a protective effect against Cy
      induced immunosuppression. COS-derived products should be further investigated
      for possible immunostimulatory applications in the food and pharmaceutical
      industries. 

PMID- 24080321
TI  - Genetic similarity between adenoid tissue and middle ear fluid isolates of
      Streptococcus pneumoniae, Haemophilus influenzae and Moraxella catarrhalis from
      Iranian children with otitis media with effusion.
AB  - BACKGROUND: Otitis media with effusion (OME) is a common disease among children,
      in the pathogenesis of which bacterial infections play a critical role. It was
      suggested that adenoid tissue could serve as a reservoir for bacterial infection,
      the eustachian tubes being the migration routes of bacteria into the middle ear
      cavity. The aim of this study was to investigate the genetic similarity between
      isolates of Streptococcus pneumoniae, Haemophilus influenzae and Moraxella
      catarrhalis, obtained from adenoid tissue and middle ear fluid. METHODS: A total
      of 60 specimens of middle ear fluids (MEFs) and 45 specimens of adenoid tissue
      were obtained from 45 children with OME. All the samples were inoculated on
      culture media for bacterial isolation and identification. The genetic similarity
      between bacterial isolates was determined by pulsed-field gel electrophoresis
      (PFGE). RESULTS: The same bacterial species were simultaneously isolated from
      adenoid tissue and MEFs of 14 patients, among which, 6 pairs of M. catarrhalis, 5
      pairs of S. pneumoniae and 3 pairs of H. influenzae were identified. CONCLUSIONS:
      Based on the genetic similarities between isolate pairs, found by PFGE analysis,
      this study suggested that M. catarrhalis, S. pneumoniae and H. influenzae
      colonize the adenoid tissue, then migrate to the middle ear cavity and, hence,
      contribute to the total pathogenesis of OME.

PMID- 24080322
TI  - Ear nose throat manifestations in hypoidrotic ectodermal dysplasia.
AB  - The ectodermal dysplasias (EDs) are a large and complex group of inherited
      disorders. In various combinations, they all share anomalies in ectodermal
      derived structures: hair, teeth, nails and sweat gland function. Clinical overlap
      is present among EDs. Few causative genes have been identified, to date. Altered
      gene expression is not limited to the ectoderm but a concomitant effect on
      developing mesenchymal structures, with modification of ectodermal-mesenchymal
      signaling, takes place. The two major categories of ED include the hidrotic and
      hypohidrotic form, the latter more frequent; they differentiate each other for
      the presence or absence of sweat glands. We report Ear Nose Throat manifestations
      of ED, linked to the reduction of mucous glands in the nasal fossae with reduced
      ciliar function, and decrease salivary glands function. Often patients report an
      increased rate of infections of the upper respiratory tract and of the ear. Nasal
      obstruction due to the presence of nasal crusting, hearing loss and throat
      hoarseness are the most represented symptoms. Environmental measures, including a
      correct air temperature and humidification, is mandatory above all in subjects
      affected by hypohidrotic form. 

PMID- 24080323
TI  - Personalized antiplatelet therapy: the wrong approach?

PMID- 24080324
TI  - Evaluation of the impact of the recent controversy over statins in France: the
      EVANS study.
AB  - BACKGROUND: The effect of statins on the prevention of cardiovascular events is
      well-established. However, a recent controversy in France questioned the value of
      statins, especially in primary prevention. AIMS: To evaluate the impact of this
      controversy on patient adherence to statin therapy and its potential clinical
      impact. METHODS: All patients on statins were recruited consecutively from
      consultations over a period of 1 month (from March 2013) by five physicians in
      three centres. Patient demographics and co-morbidities were collected and
      adherence to statin therapy was evaluated with a questionnaire. We estimated the
      number of deaths and major cardiovascular events that could be induced per year.
      RESULTS: A total of 142 patients were included: 37 in primary prevention (mean
      age, 68.0+/-13.1 years; 41% women); 105 in secondary prevention (mean age, 67.6+/
      12.1 years; 20% women). In primary prevention, 24.3% of patients intended to stop
      statins versus 8.6% in secondary prevention (P<0.001). In France, if the
      percentages of medication discontinuations following the controversy were
      actually similar to those we found in our survey, 4992 major cardiovascular
      events, including 1159 deaths, would be induced in 1 year. CONCLUSION: Recent
      controversy over statins could induce a large proportion of patients to stop
      their medication and generate a large number of major cardiovascular events.

PMID- 24080325
TI  - Cytochrome CYP2C19 polymorphism and risk of adverse clinical events in
      clopidogrel-treated patients: a meta-analysis based on 23,035 subjects.
AB  - BACKGROUND: Previous studies have investigated the relationship between CYP2C19
      polymorphism and clinical prognosis in coronary artery disease patients treated
      with clopidogrel, but the results were inconsistent. AIMS: To assess the impact
      of CYP2C19 polymorphism on the risk of adverse clinical events by performing a
      meta-analysis of relevant studies in the last few years. METHODS: Prospective
      cohort studies or post-hoc analyses of randomized controlled trials were
      identified from the databases of PubMed/Medline, EMBASE and the Cochrane Library.
      Endpoints were fatal or non-fatal myocardial infarction, cardiovascular or all
      cause death, definite or probable stent thrombosis, target vessel
      revascularization, target lesion revascularization, urgent revascularization,
      ischaemic stroke and bleeding. Pooled effects were measured by odds ratios (ORs)
      with 95% confidence intervals (CIs). RESULTS: A total of 21 studies involving
      23,035 patients were included. Compared with non-carriers of the CYP2C19 variant
      allele, the carriers were found to have an increased risk of adverse clinical
      events (OR 1.50, 95% CI 1.21-1.87; P=0.0003), myocardial infarction (OR 1.62, 95%
      CI 1.35-1.95; P<0.00001), stent thrombosis (OR 2.08, 95% CI 1.67-2.60;
      P<0.00001), ischaemic stroke (OR 2.14, 95% CI 1.36-3.38; P=0.001) and repeat
      revascularization (OR 1.35, 95% CI 1.10-1.66; P=0.004), but not of mortality
      (P=0.500) and bleeding events (P=0.930). CONCLUSION: CYP2C19 polymorphism is
      significantly associated with risk of adverse clinical events in clopidogrel
      treated patients.

PMID- 24080326
TI  - Application of transport timescales to coastal environmental assessment: a case
      study.
AB  - A numerical model based on the random walk particle tracking technique is
      developed to simulate the transport of the contaminants discharged into the
      coastal area of Guangxi, China from rivers. The model couples a 1D river flow
      module and a 2D coastal circulation module. Two transport timescales, i.e., the
      age and the arrival time, are introduced to characterize the contaminant
      transport process. The age is the time for a particle taken to enter the domain
      of interest after it left the place where the age is initially set to zero. The
      arrival time, on the other hand, is the age of the particle arriving at a
      particular place most quickly after release. It is useful for emergency responses
      to such an accident as toxic substance leakage. By the numerical model, the age
      and the arrival time under various conditions in the coastal area of Guangxi,
      China are studied in details. The age distribution and the arrival time of
      particles at a specific location are shown to closely rely on the coastal
      hydrodynamic environment in addition to the distance of the location from the
      source where particles are released. Particles released at spring tide and at ebb
      tide are found to spread more quickly than those released at neap tide and at
      flood tide, respectively. A large carrying discharge of river reduces the ages of
      the contaminants from the river concerned when transported to a place within the
      coastal area, while it has less influence on the arrival time, particularly in a
      place along the coast. 

PMID- 24080327
TI  - In situ stabilization of entrapped elemental mercury.
AB  - Elemental mercury is a dense immiscible fluid which gets entrapped as residual
      mercury in the pore spaces of the subsurface during improper disposals and
      accidental spills. This paper investigates in situ stabilization of entrapped
      elemental mercury to mercury sulphide using aqueous sodium polysulphide solution.
      Batch experiments showed 100% conversion efficiency of elemental mercury to
      mercury sulphide in a period of 96 h with sodium polysulphide/elemental mercury
      molar ratio of 1. XRD analysis identified the precipitate formed as mercury
      sulphide. Micromodel experiments, with glass beads as porous media, further
      demonstrated in situ stabilization of entrapped mercury under different residual
      mercury saturations. It was found that in a period of 10 days, 10% of entrapped
      mercury was stabilized as mercury sulphide, 0.088% was removed as dissolved
      mercury and the remaining elemental mercury was retained in porous media
      encapsulated by the newly formed mercury sulphide precipitate. However, there was
      no leaching of mercury from the micromodel effluent once stabilization was
      achieved. 

PMID- 24080328
TI  - Novel flow-through bioremediation system for removing nitrate from nursery
      discharge water.
AB  - Nitrate losses in surface runoff water from nursery production areas can be
      significant. This study evaluated the potential use of microbial-based
      (denitrification), flow-through bioreactors for their nitrate-remediation
      ability. Duplicate bioreactor systems were constructed at a local foliage plant
      nursery. Each bioreactor system consisted of four 242 L tanks with connections
      alternating between bottom and top. Each tank was filled with approximately 113 L
      of Kaldness media to provide surface area for attachment of native microflora.
      Molasses was supplied as a carbon source for denitrification and water flow rates
      through the systems ranged from 5 to 18 L min(-1) during tests. Automatic water
      samplers were used to collect composite samples every 15 min from both the inflow
      and the exit flow water. Results indicate consistent removal of 80-100% of the
      nitrate flowing into the systems. Accumulation of ammoniacal and nitrite nitrogen
      did not occur, indicating that the nitrate-nitrogen was removed from the water,
      and not simply transformed into another water-soluble species. Occasions where
      removal rates were less than 80% were usually traced to faulty delivery of the
      carbon source. Results indicate that modular microbial-based bioremediation
      systems may be a useful tool for helping water managers meet stringent nitrogen
      water quality regulations, especially at nurseries with limited space for
      expansion of water retention facilities. 

PMID- 24080329
TI  - Influence of lead-doped hydroponic medium on the adsorption/bioaccumulation
      processes of lead and phosphorus in roots and leaves of the aquatic macrophyte
      Eicchornia crassipes.
AB  - In this study, lead bioaccumulation by the living free-floating aquatic
      macrophyte Eicchornia crassipes in different hydroponic conditions with
      variations in phosphorus and lead concentrations was investigated. A set of
      growth experiments in hydroponic media doped with lead and phosphorus within a
      wide concentration range was performed for 32 days in a greenhouse. All
      experiments were carried out with periodic replacement of all nutrients and lead.
      The concentration of lead and nutrients in biomass was determined by synchrotron
      radiation-excited total reflection X-ray fluorescence. By increasing the lead
      concentration in the medium, a reduction in biomass growth was observed, but a
      higher phosphorus retention in roots and leaves was shown at lower lead
      concentrations. In addition, an increase in the amount of bioaccumulated lead and
      phosphorus in roots was observed for higher lead and phosphorus concentrations in
      the medium, reaching saturation values of 4 mg Pb g(-1) and 7 mg P g(-1),
      respectively. Four non-structural kinetic models were tested, to represent the
      bioaccumulation of lead and phosphorus in roots. Pseudo-second order and
      irreversible kinetic models described the lead bioaccumulation data well,
      however, an irreversible kinetic model better fitted phosphorus uptake in roots. 

PMID- 24080330
TI  - Optical properties of highly turbid shallow lakes with contrasting turbidity
      origins: the ecological and water management implications.
AB  - A comprehensive optical study of three highly turbid shallow lakes was presented.
      The lakes contained very high concentrations of optically active substances
      [OASs] with clear differences in total suspended solid [TSS] composition among
      them. Lakes presented elevated values of total absorption [at(lambda)] and
      scattering coefficients [b(lambda)], which translated into extremely high light
      attenuation coefficients [Kd(PAR)]. Differences among lakes in the estimation of
      Kd(PAR), using two typical estimators of light penetration (i.e., nephelometric
      turbidity [Tn] and Secchi disk [ZSD]), were analysed. Kirk's optical model was
      used to model Kd(PAR) using inherent optical properties [IOPs]. Modelled values
      of Kd(PAR) agreed very well with those measured (R(2) = 0.95). In addition,
      optical properties and Kirk's model were used to determine water quality targets
      for restoring submerged aquatic vegetation [SAV]. Based on a minimum light
      requirement for SAV of 10%, results showed that only an integrative remediation
      action, considering substantial reduction of TSS and Chl a (95%), and CDOM (50%),
      must be contemplated to improve maximum colonization depth for SAV to values
      higher than 0.7 m. On the other hand, phytoplankton absorptive characteristics
      were also studied. In these lakes, phytoplankton showed different responses to
      the nature of light competition. Some of the variation in specific phytoplankton
      absorption [aph(*)(lambda)] was explained by differences in the ratio between
      unpigmented particulate absorption and phytoplankton absorption (up to R(2) =
      0.48 for the blue band). Hydrologic optical results were discussed in terms of
      ecological and management implications.

PMID- 24080331
TI  - DNA damage and apoptosis of endometrial cells cause loss of the early embryo in
      mice exposed to carbon disulfide.
AB  - Carbon disulfide (CS2) may lead to spontaneous abortion and very early pregnancy
      loss in women exposed in the workplace, but the mechanism remains unclear. We
      designed an animal model in which gestating Kunming strain mice were exposed to
      CS2 via i.p. on gestational day 4 (GD4). We found that the number of implanted
      blastocysts on GD8 was significantly reduced by each dose of 0.1 LD50 (157.85
      mg/kg), 0.2 LD50 (315.7 mg/kg) and 0.4 LD50 (631.4 mg/kg). In addition, both the
      level of DNA damage and apoptosis rates of endometrial cells on GD4.5 were
      increased, showed definite dose-response relationships, and inversely related to
      the number of implanted blastocysts. The expressions of mRNA and protein for the
      Bax and caspase-3 genes in the uterine tissues on GD4.5 were up-regulated, while
      the expressions of mRNA and protein for the Bcl-2 gene were dose-dependently down
      regulated. Our results indicated that DNA damage and apoptosis of endometrial
      cells were important reasons for the loss of implanted blastocysts induced by
      CS2.

PMID- 24080332
TI  - Crucial role of Toll-like receptors in the zinc/nickel-induced inflammatory
      response in vascular endothelial cells.
AB  - Our previous studies indicated that zinc induced inflammatory response in both
      vascular endothelial cells and promonocytes. Here, we asked if other metals could
      cause the similar effect on vascular endothelial cells and tried to determine its
      underlying mechanism. Following screening of fifteen metals, zinc and nickel were
      identified with a marked proinflammatory effect, as determined by ICAM-1 and IL-8
      induction, on human umbilical vein endothelial cells (HUVECs). Inhibiting protein
      expression of myeloid differentiation primary response protein-88 (MyD88), a Toll
      like receptor (TLR) adaptor acting as a TLR-signaling transducer, significantly
      attenuated the zinc/nickel-induced inflammatory response, suggesting the critical
      roles of TLRs in the inflammatory response. Blockage of TLR-4 signaling by CLI
      095, a TLR-4 inhibitor, completely inhibited the nickel-induced ICAM-1 and IL-8
      expression and NFkappaB activation. The same CLI-095 treatment significantly
      blocked the zinc-induced IL-8 expression, however with no significant effect on
      the ICAM-1 expression and a minor inhibitory effect on the NFkappaB activation.
      The finding demonstrated the differential role of TLR-4 in regulation of the
      zinc/nickel-induced inflammatory response, where TLR-4 played a dominant role in
      NFkappaB activation by nickel, but not by zinc. Moreover, inhibition of NFkappaB
      by adenovirus-mediated IkappaBalpha expression and Bay 11-7025, an inhibitor of
      cytokine-induced IkappaB-alpha phosphorylation, significantly attenuated the
      zinc/nickel-induced inflammatory responses, indicating the critical of NFkappaB
      in the process. The study demonstrates the crucial role of TLRs in the
      zinc/nickel-induced inflammatory response in vascular endothelial cells and
      herein deciphers a potential important difference in NFkappaB activation via
      TLRs. The study provides a molecular basis for linkage between zinc/nickel
      exposure and pathogenesis of the metal-related inflammatory vascular disease. 

PMID- 24080333
TI  - Accessory muscles around the foot and ankle presenting as chronic undiagnosed
      pain. An illustrative case report and review of the literature.
AB  - The differential diagnosis of ankle pain is extensive. Pathology may be
      classified as intra- or extra-articular. Additionally, ankle pain may be
      traumatic or non-traumatic. One of the unusual differential diagnoses for pain in
      the ankle is an accessory muscle. Magnetic resonance imaging is the radiological
      investigation of choice. However, this is invariably reported as normal unless
      one specifically looks for an accessory muscle. The purpose of this report is to
      highlight important features of these muscles and to draw attention to this
      uncommonly reported condition. 

PMID- 24080334
TI  - Improving the de-agglomeration and dissolution of a poorly water soluble drug by
      decreasing the agglomerate strength of the cohesive powder.
AB  - Influence of ternary, poorly water-soluble components on the agglomerate strength
      of cohesive indomethacin mixtures during dissolution was studied to explore the
      relationship between agglomerate strength and extent of de-agglomeration and
      dissolution of indomethacin (Ind). Dissolution profiles of Ind from 20% Ind
      lactose binary mixtures, and ternary mixtures containing additional dibasic
      calcium phosphate (1% or 10%; DCP), calcium sulphate (10%) and talc (10%) were
      determined. Agglomerate strength distributions were estimated by Monte Carlo
      simulation of particle size, work of cohesion and packing fraction distributions.
      The agglomerate strength of Ind decreased from 1.19 MPa for the binary Ind
      mixture to 0.84 MPa for 1DCP:20Ind mixture and to 0.42 MPa for 1DCP:2Ind mixture.
      Both extent of de-agglomeration, demonstrated by the concentration of the
      dispersed indomethacin distribution, and extent of dispersion, demonstrated by
      the particle size of the dispersed indomethacin, were in descending order of
      1DCP:2Ind>1DCP:20Ind>binary Ind. The addition of calcium sulphate dihydrate and
      talc also reduced the agglomerate strength and improved de-agglomeration and
      dispersion of indomethacin. While not definitively causal, the improved de
      agglomeration and dispersion of a poorly water soluble drug by poorly water
      soluble components was related to the agglomerate strength of the cohesive matrix
      during dissolution.

PMID- 24080335
TI  - Differences in botulinum toxin dosing between patients with adductor spasmodic
      dysphonia and essential voice tremor.
AB  - OBJECTIVES: To explore possible dose differences in average botulinum toxin (BTX)
      given to patients with adductor spasmodic dysphonia (ADSD) compared with patients
      with essential voice tremor (EVT). METHODS: A retrospective study compared the
      average BTX dose injected in equal doses to the thyroarytenoid (TA) muscles of 51
      patients with ADSD with 52 patients with EVT. RESULTS: Those with ADSD received
      significantly higher total doses (6.80 +/- 2.79 units) compared with those with
      EVT (5.02 +/- 1.65 units). Dose at time of first injection, age at time of first
      injection, gender, year of first injection, and average time between injections
      were included in multivariate analysis but did not interact with total average
      dose findings. CONCLUSIONS: Patients with ADSD may need relatively higher doses
      of BTX injections to bilateral TA muscles compared with patients with EVT.

PMID- 24080336
TI  - New concepts in vocal fold imaging: a review.
AB  - OBJECTIVE: To review new imaging technology potentially useful in the clinical
      practice of laryngology. HYPOTHESIS: Narrow band imaging, iScan (Pentax Medical
      Company, Montvale, NJ), optical computed tomography, and confocal microscopy have
      potential value for enhancing diagnosis of laryngeal pathology. DESIGN:
      Literature review. METHODS: Literature search of computer databases including
      MEDLINE and PubMed. RESULTS: A review of 50 articles suggests that new imaging
      technologies may enhance clinical diagnostic capabilities. CONCLUSION: The
      probable value of new imaging technologies suggests that further research is
      needed to refine these technologies and define their clinical efficacy.

PMID- 24080337
TI  - Microcomputed tomography visualization of the cricoarytenoid joint cavity in
      cadavers.
AB  - OBJECTIVES: To visualize the cricoarytenoid joint (CAJ) cavity of the human
      cadaver and to correlate its appearance to the CAJ capsule. STUDY DESIGN:
      Prospective. METHODS: A total of 26 cadavers were used for microcomputed
      tomography arthrography, histology, and epoxy sheet plastination examinations.
      RESULTS: (1) The dimension of the CAJ cavity was much larger than the articular
      surfaces; (2) The posterior capsule of the CAJ was significantly strengthened,
      contained rich elastin fibers, and shared a common attachment with the posterior
      cricoarytenoid muscle; (3) The arytenoid cartilage was distanced from the cricoid
      cartilage at the superomedial aspect of the CAJ. CONCLUSIONS: This study
      demonstrates that the posterior fibrous capsule is the primary passive stabilizer
      of the CAJ and suggests that in addition to the gliding, rucking, and rotation, a
      visor-like jumping of the arytenoid cartilage on the cricoid cartilage may
      provide further adjustments in motions of the vocal fold. The finding of this
      study has implications for the biomechanics of the CAJ motion; the differential
      diagnosis of CAJ disorders, such as CAJ dislocation and subluxation; and surgical
      correction of the CAJ dysfunction.

PMID- 24080339
TI  - Antiproliferative and proapoptotic activities of 4-hydroxybenzoic acid-based
      inhibitors of histone deacetylases.
AB  - Histone acetyltransferases (HATs) and histone deacetylases (HDACs) regulate
      cellular processes by modifying the acetylation status of many proteins.
      Pathologically altered HDAC activity contributes to cancer development and thus
      characterization of novel acetylation modulators is important for future anti
      cancer therapies. In this study, we identified three novel 4-hydroxybenzoic acid
      derivatives as pan-HDAC inhibitors that increased protein acetylation levels,
      arrested cell cycle progression and triggered apoptotic cell death, without
      affecting viability of normal cells. Our data support the potential of 4
      hydroxybenzoic acid derivatives as pan-HDAC inhibitors with anticancer
      properties.

PMID- 24080338
TI  - Pro-survival and pro-growth effects of stress-induced nitric oxide in a prostate
      cancer photodynamic therapy model.
AB  - We discovered recently that human breast cancer cells subjected to photodynamic
      therapy (PDT)-like oxidative stress localized in mitochondria rapidly upregulated
      nitric oxide synthase-2 (NOS2) and nitric oxide (NO), which increased resistance
      to apoptotic photokilling. In this study, we asked whether human prostate cancer
      PC-3 cells would exploit NOS2/NO similarly and, if so, how proliferation of
      surviving cells might be affected. Irradiation of photosensitized PC-3 cells
      resulted in a rapid (<1 h), robust (~12-fold), and prolonged (~20 h) post
      irradiation upregulation of NOS2. Caspase-3/7 activation and apoptosis were
      stimulated by NOS2 inhibitors and a NO scavenger, implying that induced NO was
      acting cytoprotectively. Cyclic GMP involvement was ruled out, whereas
      suppression of pro-apoptotic JNK and p38 MAPK activation was clearly implicated.
      Cells surviving photostress grew back ~2-times faster than controls. NOS2
      inhibition prevented this and the large increase in cell cycle S-phase occupancy
      observed after irradiation. Thus, photostress upregulation of NOS/NO elicited
      both a pro-survival and pro-growth response, both of which could compromise
      clinical PDT efficacy unless suppressed, e.g. by pharmacological intervention
      with a NOS2 inhibitor.

PMID- 24080340
TI  - Identification and analysis of CD133(+) melanoma stem-like cells conferring
      resistance to taxol: An insight into the mechanisms of their resistance and
      response.
AB  - The presence and the involvement of cancer stem-like cells (CSCs) in tumor
      initiation and progression, and chemo-resistance are documented. Herein, we
      functionally analyzed melanoma stem-like cells (MSC)/CD133(+) cells on their
      resistance and response to taxol-induced apoptosis. Besides being taxol
      resistant, the CD133(+) cells demonstrated a growth advantage over the CD133(-)
      subpopulation. Taxol induced apoptosis on CD133(-) cells, but not on CD133(+)
      cells. In the CD133(-) subpopulation, the exposure to taxol induced the
      activation of apoptosis signal-regulating kinase1 (ASK1)/c-jun-N-terminal kinase
      (JNK), p38, extracellular signal regulated kinase (ERK) pathways and Bax
      expression, while in CD133(+) cells taxol was able only to enhance the activity
      of the ERK pathway. In CD133(+) cells, the direct gene transfer of Bax overcame
      the acquired resistance to taxol. Taken together, our data provide an insight
      into the mechanistic cascade of melanoma resistance to taxol and suggest Bax gene
      transfer as a complementary approach to chemotherapy.

PMID- 24080341
TI  - Spirituality in men with advanced prostate cancer: "it's a holistic thing . . .
      it's a package".
AB  - Spirituality is often regarded as being helpful during an unwell person's journey
      but definitions of the concept can be confusing, and its use synonymously with
      religion can be misleading. This research sought to answer the question, "What is
      the nature of spirituality in men with advanced prostate cancer," and to discover
      the role spirituality may have in these men as they face the challenges of living
      with their disease. A qualitative approach and narrative method was used to
      explore the spirituality of nine men with advanced prostate cancer who
      volunteered to participate and to tell the story of their cancer journey with
      particular focus on their spirituality. The study found that spirituality for
      these men, who were all Caucasians, was a "holistic thing" that involved
      physical, psychosocial, and spiritual matters that enabled them to transcend the
      everyday difficulties of their journey. Through their spirituality they obtained
      greater comfort and peace of mind during what was for many of them a very
      traumatic time. The central theme in the men's stories was that of connectedness
      to themselves, to their partners, sometimes to a higher being, to other people
      such as their family and friends, and to other aspects of their lives. 

PMID- 24080342
TI  - A legacy building model for holistic nursing.
AB  - This pilot project was an effort to record the historical roots, development, and
      legacy of holistic nursing through the visionary spirit of four older American
      Holistic Nurses Association (AHNA) members. The aim was twofold: (a) to capture
      the holistic nursing career experiences of elder AHNA members and (b) to begin to
      create a Legacy Building Model for Holistic Nursing. The narratives will help
      initiate an ongoing, systematic method for the collection of historical data and
      serve as a perpetual archive of knowledge and inspiration for present and future
      holistic nurses. An aesthetic inquiry approach was used to conduct in-depth
      interviews with four older AHNA members who have made significant contributions
      to holistic nursing. The narratives provide a rich description of their personal
      and professional evolution as holistic nurses. The narratives are presented in an
      aesthetic format of the art forms of snapshot, pastiche, and collage rather than
      traditional presentations of research findings. A synopsis of the narratives is a
      dialogue between the three authors and provides insight for how a Legacy Model
      can guide our future. Considerations for practice, education, and research are
      discussed based on the words of wisdom from the four older holistic nurses.

PMID- 24080343
TI  - Water and tissue equivalency of some gel dosimeters for photon energy absorption.
AB  - The mass energy absorption coefficients,, effective atomic numbers for photon
      energy absorption, ZPEAeff, and effective electron numbers for photon-energy
      absorption, NPEAeff, is calculated for 14 polymer gel dosimeter, five gel
      dosimeter, soft tissue and water, in the energy range from 1 keV to 20 MeV. The
      ZPEAeff(Gel)/ZPEAeff(Tissue) and NPEAeff(Gel)/NPEAeff (Tissue) are used to
      evaluate the tissue equivalency.

PMID- 24080344
TI  - Antigens in lymphoma development--current knowledge and future directions.
AB  - Lymphomas are a very heterogeneous group of tumors of mature lymphoid cells with
      quite different morphology, genetics and clinical characteristics, which is also
      reflected in the numerous entities and sub-entities defined in the most recent
      WHO classification. Today, it is well-established that lymphomas can evolve due
      to both 'cell-intrinsic' factors (e.g. acquired genomic aberrations) and 'cell
      extrinsic' factors (e.g. microenvironmental stimuli), although for most lymphoma
      subtypes the precise implicated mechanisms remain to be elucidated. In this
      thematic issue, a series of reviews have been collected focusing on key evidence
      for (i) direct or indirect links between antigens and lymphoma development; and,
      (ii) activated signaling pathways that play an essential role in tumor evolution
      and progression. Finally, strategies for the management of lymphomas developing
      due to viral and bacterial infection as well as novel promising therapies
      designed to hit specific cellular pathways (e.g. B-cell receptor inhibitors) will
      be summarized and discussed. Altogether, this issue will give the reader
      important insights into the current knowledge of the diverse mechanisms that come
      into play during lymphoma development as well as clues to future directions
      within this broad and intense research field. 

PMID- 24080345
TI  - Urinary incontinence in pregnant women and its relation with socio-demographic
      variables and quality of life.
AB  - OBJECTIVE: To investigate the occurrence of urinary incontinency (UI) in pregnant
      women and its relationship with socio-demographic variables and quality of life.
      METHODS: A descriptive cross-sectional multicenter study was conducted to
      investigate 495 women using the International Consultation on Incontinence
      Questionnaire - Short Form (ICIQ-SF). The survey was conducted on the same day of
      delivery, with the volunteers still in the maternity ward. Statistical analysis
      of the comparison between groups 1 (incontinence) and 2 (continent) was done
      using chi-square test for comparison of proportions of women with and without
      urinary incontinency and logistic regression analysis. RESULTS: From the total of
      495 women studied, 352 (71%) reported having had UI during the last four weeks of
      pregnancy. Group 1 presented the ICIQ-SF median score of 11 (range 3-21),
      considered as severe impact in quality of life. Logistic regression analysis
      showed that there was a closer relation between the self-report of UI with the
      following variables: level of education below 8 years (OR: 2.99; p < 0.001),
      black women (OR: 2.32; p= 0.005), women with more than 3 children (OR: 4.93; p <
      0.001), obese (OR: 4.22; p < 0.001) and normal vaginal delivery (OR: 2.59; p <
      0.001). CONCLUSION: The majority of pregnant women have UI, negatively affecting
      the quality of their lives.

PMID- 24080346
TI  - Fetal and neonatal deaths among cases of maternal near miss.
AB  - OBJECTIVE: To determine the prevalence of fetal and neonatal deaths among
      patients with maternal near miss and the factors associated with this fatal
      outcome. METHODS: The authors conducted a descriptive, cross-sectional, analyzing
      medical records of patients admitted to the ICU of a tertiary obstetric Recife
      (Brazil), between January 2007 and December 2010, who had at least one criterion
      of near miss defined by WHO. Statistical analysis was performed with Epi-Info
      3.3.2, using chi-square and Fisher's exact test, considering a significance level
      of 5%. For multivariate analysis was constructed as a hierarchical model with the
      response variable fetal and neonatal deaths. RESULTS: We included 246 cases of
      maternal near miss. Among women in the study, hypertensive disorders occurred in
      62.7% to 41.2% in HELLP syndrome and the laboratory criteria for near miss in
      59.6%. There were 48 (19.5%) stillbirths and 19 (7.7%) neonatal deaths. After
      analyzing the variables that remained statistically associated with fetal and
      neonatal deaths were: severe preeclampsia, placental abruption, endometritis,
      cesarean delivery, prematurity and the laboratory criteria for maternal near
      miss. CONCLUSION: The high incidence of fetal and neonatal deaths among patients
      with maternal near miss. Among these women there is an overlap of factors
      contributing to this fatal outcome, in our study, those who had severe
      preeclampsia, placental abruption, endometritis, premature birth or laboratory
      criteria positively associated with deaths.

PMID- 24080347
TI  - Primary dysmenorrhea: treatment.

PMID- 24080349
TI  - Complex regional pain syndrome type I: incidence and risk factors in patients
      with fracture of the distal radius.
AB  - OBJECTIVE: To examine the incidence and predictors of complex regional pain
      syndrome type I (CRPS I) after fracture of the distal radius. DESIGN: Prospective
      study. SETTING: University hospital. PARTICIPANTS: A consecutive sample of
      patients (N=90) with fracture of the distal radius treated by closed reduction
      and casting. INTERVENTIONS: Not applicable. MAIN OUTCOME MEASURES: Occurrence of
      CRPS I, occurrence of pain, wrist and hand range of motion, radiographic
      measures, Patient-Rated Wrist Evaluation, Hospital Anxiety and Depression Scale,
      and Medical Outcomes Study 36-Item Short-Form Health Survey at baseline and 1, 3,
      6, and 9 months follow-up. RESULTS: CRPS I occurred in 29 patients (32.2%) with a
      mean delay +/- SD of 21.7+/-23.7 days from cast removal. Univariate analyses
      found significant differences between patients with CRPS I and patients without
      CRPS I at baseline for sex (P=.021), socioeconomic level (P=.023), type of trauma
      (P=.05), pain at rest and activity (P=.006 and P<.001, respectively), wrist
      dorsiflexion and pronation (P=.002 and P=.001, respectively), finger flexion
      (P=.047), thumb opposition (P=.002), function of the hand (P<.001), and physical
      quality of life (QOL) (P=.013). Logistic regression showed that risk for CRPS I
      was higher in cases of women (odds ratio [OR]=5.774; 95% confidence interval
      [CI], 1.391-23.966), medium and low energy trauma patients (OR=7.718; 95% CI,
      1.136-52.44), patients with a Medical Outcomes Study 36-Item Short-Form Health
      Survey physical functioning score <40 (OR=4.931; 95% CI, 1.428-17.025), and
      patients with Patient-Rated Wrist Evaluation pain subscale score >16 (OR=12.192;
      95% CI, 4.484-43.478). CONCLUSIONS: CRPS I occurs frequently during the third and
      fourth week after cast removal, especially in women who report severe pain and
      impairment of physical QOL. Additional prospective studies are required to verify
      these findings in comminuted and operated fractures of the distal radius.

PMID- 24080348
TI  - Network of movement and proximity sensors for monitoring upper-extremity motor
      activity after stroke: proof of principle.
AB  - OBJECTIVE: To test the convergent validity of an objective method, Sensor-Enabled
      Radio-frequency Identification System for Monitoring Arm Activity (SERSMAA), that
      distinguishes between functional and nonfunctional activity. DESIGN: Cross
      sectional study. SETTING: Laboratory. PARTICIPANTS: Participants (N=25) were
      >=0.2 years poststroke (median, 9) with a wide range of severity of upper
      extremity hemiparesis. INTERVENTIONS: Not applicable. MAIN OUTCOME MEASURES:
      After stroke, laboratory tests of the motor capacity of the more-affected arm
      poorly predict spontaneous use of that arm in daily life. However, available
      subjective methods for measuring everyday arm use are vulnerable to self-report
      biases, whereas available objective methods only provide information on the
      amount of activity without regard to its relation with function. The SERSMAA
      consists of a proximity-sensor receiver on the more-affected arm and multiple
      units placed on objects. Functional activity is signaled when the more-affected
      arm is close to an object that is moved. Participants were videotaped during a
      laboratory simulation of an everyday activity, that is, setting a table with
      cups, bowls, and plates instrumented with transmitters. Observers independently
      coded the videos in 2-second blocks with a validated system for classifying more
      affected arm activity. RESULTS: There was a strong correlation (r=.87, P<.001)
      between time that the more-affected arm was used for handling objects according
      to the SERSMAA and functional activity according to the observers. CONCLUSIONS:
      The convergent validity of SERSMAA for measuring more-affected arm functional
      activity after stroke was supported in a simulation of everyday activity.

PMID- 24080350
TI  - Emerging multiple reassortant H5N5 avian influenza viruses in ducks, China, 2008.
AB  - Three highly pathogenic H5N5 avian influenza viruses (HPAI),
      A/duck/Guangdong/wy11/2008 (WY11), A/duck/Guangdong/wy19/2008 (WY19), and
      A/duck/Guangdong/wy24/2008 (WY24) were isolated from ducks in southern China in
      April 2008. Here, we characterized these viruses by performing sequencing and
      phylogenetic analyses of their viral genes, assessing their virulence in ducks
      and mice, and performing cross-protection experiments in chickens. Sequence
      analysis revealed that the HA genes of these H5N5 viruses showed 97.1-97.8%
      homology to A/wild duck/Hunan/211/2005 (H5N1) influenza virus and that their NA
      genes showed 96.4-96.8% nucleotide identity to the NA gene of
      A/duck/Hunan/5613/2003 (H6N5) influenza virus, which belongs to the Eurasian
      lineage. Genotypic analysis indicated that these H5N5 viruses were multiple
      reassortants among H5N1, H5N2, H6N2, and H6N5 viruses. The analysis of HA clade
      showed that these H5N5 viruses are clustering into clade 2.3.4. In animal
      experiments, these H5N5 viruses caused 50% mortality in ducks and 100% mortality
      in chickens. In cross-protection experiments, the clade 2.3.2 avian influenza
      vaccine could provide only 75% protection with chickens against H5N5 virus
      challenge. Moreover, the H5N5 virus replicated efficiently in the lungs of mice,
      which suggested that the H5N5 viruses have the potential to infect mammalian
      hosts. Since ducks have served as reassortant vessels, playing pivotal roles in
      the generation of new subtypes of influenza viruses, it is important to monitor
      the emergence of this novel subtype of influenza viruses in waterfowl to
      understand their ecology and evolution and to control the spread of new viruses. 

PMID- 24080351
TI  - Characterization of Lactococcus lactis isolates from bovine mastitis.
AB  - Lactococcus lactis is a widely used mesophilic dairy starter and has been
      included in the Qualified Presumption of Safety (QPS) list of the European Food
      Safety Authority. However, it is increasingly found as the cause of human or
      animal infections, such as bovine mastitis, probably due to the improvement of
      the identification of the infective microorganisms. Since there are some grounds
      to suspect that at least certain variants of L. lactis may cause animal or human
      diseases, it is important to properly identify the differences between the
      strains associated with infections and the safe starter strains. Bovine mastitis
      isolates and dairy starter strains were genotypically characterized and clustered
      by the 16S rRNA gene sequence and RAPD-PCR fingerprint patterns, and
      phenotypically characterized by their tolerance to different stress conditions
      typically found in the intestinal tract of mammals, the carbohydrate- and
      antibiotic resistance profile, as well as the in vitro adhesion capacity to udder
      epithelial cells. Genotypically, there were no differences between the mastitis
      isolates and the dairy starter strains. However, there were clear phenotypic
      distinctions between mastitis isolates and typical starter strains, the former
      showing an increased tolerance to temperature, lysozyme, bile salts, pH and
      antibiotics, as well as improved carbohydrate fermentation capacity, and in vitro
      adhesion to udder epithelial cells. Although these differences might not be
      considered as actual virulence factors, they improve the ability of the strain to
      survive in the body of homeothermic animals and, interestingly, are also typical
      properties associated with potential probiotic strains. 

PMID- 24080352
TI  - Gene expression analysis of Salmonella enterica SPI in macrophages indicates
      differences between serovars that induce systemic disease from those normally
      causing enteritis.
AB  - Global gene expression of the invasive Salmonella serovars S. Enteritidis and S.
      Typhimurium, and the less-invasive S. Infantis and S. Hadar was studied during
      infection of a chicken macrophage cell line. Major functional gene groups
      responsible for intracellular physiological changes were regulated similarly in
      all four serovars. However, SPI1 and SPI4 genes of S. Enteritidis and S.
      Typhimurium were strongly repressed in the macrophages whereas S. Infantis, S.
      Hadar and other similar serovars maintained up-regulation of these gene sets.
      This phenomenon may explain some of the biological differences between invasive
      and non-invasive Salmonella serovars. 

PMID- 24080353
TI  - Pudendal nerve neuralgia after hip arthroscopy: retrospective study and
      literature review.
AB  - INTRODUCTION: Pudendal nerve neurapraxia is a classic complication after traction
      on the fracture table. Diagnosis, however, is difficult and often overlooked,
      especially after arthroscopy in traction on fracture table; incidence is
      therefore not known exactly. HYPOTHESIS: The study hypothesis was that incidence
      of pudendal nerve neuropathy exceeds 1% after hip arthroscopy. MATERIALS AND
      METHODS: Results for 150 patients (79 female, 71 male) undergoing hip arthroscopy
      between 2000 and 2010 were analyzed retrospectively. The principal assessment
      criterion was onset of pudendal neuralgia. Secondary criteria were risk factors
      (history, surgery time, type of anesthesia), associated complications, onset to
      diagnosis interval and pattern of evolution. RESULTS: At a mean 93 months' follow
      up, there were 3 cases (2 women, 1 man) (2%) of pure sensory pudendal neuralgia;
      2 concerned labral lesion resection and 1 osteochondromatosis. Surgery time
      ranged from 60 to 120min, under general anesthesia with curarization. Time to
      diagnosis was 3 weeks. No complementary examinations were performed. Spontaneous
      resolution occurred at 3 weeks to 6 months. No significant risk factors emerged.
      CONCLUSION: The present study found 2% incidence of pudendal neuralgia, with no
      risk factors emerging from analysis. Prevention involves limiting traction force
      and duration by using a large pelvic support (diameter>8-10cm). Patient
      information and postoperative screening should be systematic. LEVEL OF EVIDENCE:
      Level IV. Retrospective study.

PMID- 24080354
TI  - Defensive chemicals of tawny crazy ants, Nylanderia fulva (Hymenoptera:
      Formicidae) and their toxicity to red imported fire ants, Solenopsis invicta
      (Hymenoptera: Formicidae).
AB  - Nylanderia fulva (Mayr) has been reported as being able to displace Solenopsis
      invicta Buren, one of the most aggressive invasive ants in the world. Like S.
      invicta, N. fulva use chemical secretions in their defense/offense, which may
      contribute to their observed superior competition ability. In this study, the
      defensive chemicals of N. fulva workers and their toxicity against S. invicta
      workers were investigated. Like other formicine ants, N. fulva workers produce
      formic acid in their poison glands and 2-ketones and alkanes in Dufour glands. Of
      these, undecane and 2-tridecanone are two principal compounds in the Dufour
      gland. Topical LD50 values of 2-tridecanone and undecane against S. invicta
      workers ranged from 18.51 to 24.67 MUg/ant and 40.39 to 84.82 MUg/ant,
      respectively. Undecane and 2-tridecanone had significantly higher contact
      toxicity than formic acid, whereas formic acid had significantly higher
      fumigation toxicity than undecane and 2-tridecanone. The combination of 2
      tridecanone as a contact toxin and formic acid as a fumigant significantly
      decreased KT50 values when compared to those of individual compounds. N. fulva
      does not seem unique in terms of the chemistry of its defensive secretion as
      compared to other formicine ants. However, this ant contained more than two
      orders of magnitude of formic acid (wt/wt) than other formicine ants and one
      order of magnitude of 2-tridecanone than the common crazy ant, Paratrechina
      longicornis (Latreille). The quantity, rather than quality, of the chemical
      secretion may contribute to the superior competition ability of N. fulva. 

PMID- 24080355
TI  - Effect of Bothrops bilineata snake venom on neutrophil function.
AB  - The aim of the study was to evaluate the in vitro effects of Bothrops bilineata
      crude venom (BbV) on isolated human neutrophil function. We proved that BbV isn't
      toxic towards human neutrophils. During an incubation of human neutrophils with
      BbV hydrogen peroxide was produced. Moreover, BbV was able to stimulate
      neutrophil release of proinflammatory mediators such as IL-8 and IL-6 as well as
      PGE2 and NETs liberation. There is no data in the literature showing the effect
      of BbV on the production of IL-6 and IL-8 or NETs liberation by isolated human
      neutrophils. Taken together our results testify that BbV triggers relevant
      proinflammatory events in human neutrophils. 

PMID- 24080356
TI  - Characterizing the evolution and functions of the M-superfamily conotoxins.
AB  - Conotoxins from cone snails are valuable in physiology research and therapeutic
      applications. Evolutionary mechanisms of conotoxins have been investigated in
      several superfamilies, but there is no phylogenetic analysis on M-superfamily
      conotoxins. In this study, we characterized identical sequences, gene structure,
      novel cysteine frameworks, functions and evolutionary mechanisms of M-superfamily
      conotoxins. Identical M-superfamily conotoxins can be found in different Conus
      species from the analysis of novel 467 M-superfamily conotoxin sequences and
      other published M-superfamily conotoxins sequences. M-superfamily conotoxin genes
      consist of two introns and three exons from the results of genome walking.
      Eighteen cysteine frameworks were identified from the M-superfamily conotoxins,
      and 10 of the 18 may be generated from framework III. An analysis between diet
      types and phylogeny of the M-superfamily conotoxins indicate that M-superfamily
      conotoxins might not evolve in a concerted manner but were subject to birth-and
      death evolution. Codon usage analysis shows that position-specific codon
      conservation is not restricted to cysteines, but also to other conserved
      residues. By analysing primary structures and physiological functions of M
      superfamily conotoxins, we proposed a hypothesis that insertions and deletions,
      especially insertions in the third cysteine loop, are involved in the creation of
      new functions and structures of the M-superfamily conotoxins. 

PMID- 24080357
TI  - Mutation in CYP27A1 identified in family with coronary artery disease.
AB  - Coronary artery disease (CAD) is a leading cause of death worldwide. Myocardial
      infarction is the most severe outcome of CAD. Despite extensive efforts, the
      genetics of CAD is poorly understood. We aimed to identify the genetic cause of
      CAD in a pedigree with several affected individuals. Exome sequencing led to
      identification of a mutation in CYP27A1 that causes p.Arg225His in the encoded
      protein sterol 27-hydroxylase as the likely cause of CAD in the pedigree. The
      enzyme is multifunctional, and several of its functions including its functions
      in vitamin D metabolism and reverse cholesterol transport (RCT) are relevant to
      the CAD phenotype. Measurements of vitamin D levels suggested that the mutation
      does not affect CAD by affecting this parameter. We suggest that the mutation may
      cause CAD by affecting RCT. Screening of all coding regions of the CYP27A1 in 100
      additional patients led to finding four variations (p.Arg14Gly, p.Arg26Lys,
      p.Ala27Arg, and p.Val86Met) in seven patients that may contribute to their CAD
      status. CYP27A1 is the known causative gene of cerebrotendinous xanthomatosis, a
      disorder which is sometimes accompanied by early onset atherosclerosis. This and
      the observation of potentially harmful variations in unrelated CAD patients
      provide additional evidence for the suggested causative role of the p.Arg225His
      mutation in CAD.

PMID- 24080358
TI  - MCPH1 deletion in a newborn with severe microcephaly and premature chromosome
      condensation.
AB  - A newborn with severe microcephaly and a history of parental consanguinity was
      referred for cytogenetic analysis and subsequently for genetic evaluation. While
      a 46,XY karyotype was eventually obtained, premature chromosome condensation was
      observed. A head MRI confirmed primary microcephaly. This combination of features
      focused clinical interest on the MCPH1 gene and directed genetic testing by
      sequence analysis and duplication/deletion studies disclosed a homozygous
      deletion of exons 1-11 of the MCPH1 gene. This case illustrates a strength of
      standard cytogenetic evaluation in directing molecular testing to a single target
      gene in this disorder, allowing much more rapid diagnosis at a substantial cost
      savings for this family. 

PMID- 24080359
TI  - Association of novel biomarkers with future cardiovascular events and the
      influence of ethnicity.

PMID- 24080360
TI  - Further elaboration of the relationship between heart rate variability and plasma
      cholesterol: response to Kawada.

PMID- 24080361
TI  - Bifurcational lesions: do we really need dedicated devices?
AB  - Provisional stenting of the side-branch is the universally accepted gold standard
      while there is still controversy on the role of kissing balloon dilatation.
      During treatment of bifurcation, most experienced operators prefer to correct the
      carina shift leading to ostial stenosis after the deployment of the main vessel
      stent by apposing the free struts jailing the origin of the side-branch to the
      ostium of the side-branch. Recrossing the struts of a previously deployed stent
      with a wire and an appropriately sized balloon can prove challenging and is
      occasionally unsuccessful, mainly because the balloon tip hits a stent strut.
      Thanks to its short beveled tip and the torquable shaft, the glider balloon can
      be easily rotated during advancement and might offer a rapid solution during
      treatment of complex bifurcational lesions. 

PMID- 24080362
TI  - NT-proB natriuretic peptide, risk factors and asymptomatic left ventricular
      dysfunction: results of the SCReening Evaluation of the Evolution of New Heart
      Failure study (SCREEN-HF).
AB  - BACKGROUND: We assessed left ventricular dysfunction in a population at high risk
      for heart failure (HF), and explored associations between ventricular function,
      HF risk factors and NT-proB natriuretic peptide (NT-proBNP). METHODS AND RESULTS:
      3550 subjects at high risk for incident HF (>=60 years plus >=1 HF risk factor),
      but without pre-existing HF or left ventricular dysfunction, were recruited.
      Anthropomorphic data, medical history and blood for NT-proBNP were collected.
      Participants at highest risk (n = 664) (NT-proBNP highest quintile; >30.0 pmol/L)
      and a sample (n = 51) from the lowest NT-proBNP quintile underwent
      echocardiography. Participants in the highest NT-proBNP quintile, compared to the
      lowest, were older (74 years vs. 67 years; p < 0.001) and more likely to have
      coronary artery disease, stroke or renal impairment. In the top NT-proBNP
      quintile (n = 664), left ventricular systolic impairment was observed in 6.6%
      (95% CI: 4 to 8%) of participants and was associated with male gender, coronary
      artery disease, hypertension and NT-proBNP. At least moderate diastolic
      dysfunction was observed in 24% (95% CI 20 to 27%) of participants and was
      associated with diabetes and NT-proBNP. In this high risk population, NT-proBNP
      was associated with left ventricular systolic impairment (p < 0.001) and moderate
      to severe diastolic dysfunction (p < 0.001) after adjustment for age, gender,
      coronary artery disease, diabetes, hypertension and obesity. CONCLUSION: A high
      burden of ventricular dysfunction was observed in this high risk group. Combining
      NT-proBNP and HF risk factors may identify those with ventricular dysfunction.
      This would allow resources to be focused on those at greatest risk of progression
      to overt HF.

PMID- 24080363
TI  - The bilaterian forebrain: an evolutionary chimaera.
AB  - The insect, annelid and vertebrate forebrains harbour two major centres of output
      control, a sensory-neurosecretory centre releasing hormones and a primordial
      locomotor centre that controls the initiation of muscular body movements. In
      vertebrates, both reside in the hypothalamus. Here, we review recent comparative
      neurodevelopmental evidence indicating that these centres evolved from separate
      condensations of neurons on opposite body sides ('apical nervous system' versus
      'blastoporal nervous system') and that their developmental specification involved
      distinct regulatory networks (apical six3 and rx versus mediolateral nk and pax
      gene-dependent patterning). In bilaterian ancestors, both systems approached each
      other and became closely intermingled, physically, functionally and
      developmentally. Our 'chimeric brain hypothesis' sheds new light on the vast
      success and rapid diversification of bilaterian animals in the Cambrian and
      revises our understanding of brain architecture. 

PMID- 24080364
TI  - Synthesis, characterization and in vitro screening on bacterial, fungal and
      malarial strain of piprazinyl cyano biphenyl based compounds.
AB  - A series of eight 4'-[4-(3-substituted phenyl-acryloyl)-piprazin-1-ylmethyl]
      biphenyl-2-carbonitrile were synthesized using 4'-Bromomethyl-biphenyl-2
      carbonitrile and 4-Acetyl piprazine as a starting material. Furthermore, there
      has been some additional work done investigating effects of these derivatives on
      biological activities on bacterial, fungal and malarial strain. Synthesized
      compounds were characterized using FTIR, (1)H NMR and (13)C NMR spectrometry.
      These compounds shows good antimalarial, antibacterial and antifungal activity.
      In fact some compounds are more potent than standard drug quinine and Ampicillin
      some are with comparable activity with Ampicillin and quinine. 

PMID- 24080365
TI  - Insulin-like growth factor-1 receptor-mediated inhibition of A-type K(+) current
      induces sensory neuronal hyperexcitability through the phosphatidylinositol 3
      kinase and extracellular signal-regulated kinase 1/2 pathways, independently of
      Akt.
AB  - Although IGF-1 has been implicated in mediating hypersensitivity to pain, the
      underlying mechanisms remain unclear. We identified a novel functional of the IGF
      1 receptor (IGF-1R) in regulating A-type K(+) currents (IA) as well as membrane
      excitability in small trigeminal ganglion neurons. Our results showed that IGF-1
      reversibly decreased IA, whereas the sustained delayed rectifier K(+) current was
      unaffected. This IGF-1-induced IA decrease was associated with a hyperpolarizing
      shift in the voltage dependence of inactivation and was blocked by the IGF-1R
      antagonist PQ-401; an insulin receptor tyrosine kinase inhibitor had no such
      effect. An small interfering RNA targeting the IGF-1R, or pretreatment of neurons
      with specific phosphatidylinositol 3-kinase (PI3K) inhibitors abolished the IGF-1
      induced IA decrease. Surprisingly, IGF-1-induced effects on IA were not regulated
      by Akt, a common downstream target of PI3K. The MAPK/ERK kinase inhibitor U0126,
      but not its inactive analog U0124, as well as the c-Raf-specific inhibitor
      GW5074, blocked the IGF-1-induced IA response. Analysis of phospho-ERK (p-ERK)
      showed that IGF-1 significantly activated ERK1/2 whereas p-JNK and p-p38 were
      unaffected. Moreover, the IGF-1-induced p-ERK1/2 increase was attenuated by PI3K
      and c-Raf inhibition, but not by Akt blockade. Functionally, we observed a
      significantly increased action potential firing rate induced by IGF-1;
      pretreatment with 4-aminopyridine abolished this effect. Taken together, our
      results indicate that IGF-1 attenuates IA through sequential activation of the
      PI3K- and c-Raf-dependent ERK1/2 signaling cascade. This occurred via the
      activation of IGF-1R and might contribute to neuronal hyperexcitability in small
      trigeminal ganglion neurons. 

PMID- 24080366
TI  - The regulatory role of the adrenergic agonists phenylephrine and isoproterenol on
      fetal hemoglobin expression and erythroid differentiation.
AB  - It has been reported that various endocrine hormones exert prominent effects on
      erythropoiesis. We conducted experiments to identify the mechanisms involved in
      the regulatory functions of adrenergic signaling on erythroid differentiation and
      the expression of hemoglobin genes. The reactivation of fetal hemoglobin (HbF)
      expression is also an important therapeutic option in patients with hemoglobin
      disorders. We determined that the adrenergic agonists phenylephrine (PE) and
      isoproterenol (ISO) can induce the production of beta-hemoglobin embryonic 1
      (hbbe1) mRNA and protein in adult zebrafish erythrocytes. Elevated levels of HbF
      mRNA and protein were also observed in human K562 cells after the adrenergic
      agonist treatments. In addition, elevated levels of histone acetylation were
      observed in both the PE- and the ISO-treated K562 cells. Additionally, our data
      further indicate that the induction effects of the adrenergic agonists on HbF
      synthesis and erythroid differentiation in K562 cells are mainly mediated by the
      p38 MAPK/cAMP response element binding pathway. In summary, the present study
      identifies the role of the adrenergic agonists PE and ISO on p38 MAPK and ERK
      signaling for the stimulation of HbF production and erythroid differentiation. 

PMID- 24080368
TI  - The presence of adenosine A2a receptor in thyrocytes and its involvement in
      Graves' IgG-induced VEGF expression.
AB  - Goitrogenesis in Graves' disease (GD) has been attributed to anti-TSH receptor
      antibody stimulation. Recently, a role for adenosine A2a receptor (A2aR) in
      goiter formation was reported in the thyroglobulin-A2aR transgenic mice. However,
      it is unclear whether A2aR is expressed in the thyroid and whether it is
      associated with the pathogenesis of goiter in GD. Here, we confirmed the
      expression of A2aR in FRTL-5 cells, primary normal human thyrocytes (both sexes
      were used without regard to sex), and thyroid tissue (both sexes were used
      without regard to sex) by PCR, Western blotting, immunohistochemistry, and
      immunofluorescence. After treatments with A2aR-specific agonist 2-p-(2
      Carboxyethyl)phenethylamino-5'-N-ethylcarboxamidoadenosine or GD IgG, the mRNA
      and protein levels of vascular endothelial growth factor (VEGF), a growth factor
      related to goitrogenesis, were evaluated along with upstream signaling pathways.
      A2aR activation and GD IgG promoted the expression of VEGF in thyrocytes, which
      was accompanied by the activation of cAMP/protein kinase A/phosphorylated-cAMP
      response element-binding protein, peroxisome proliferator-activated receptor
      gamma coactivator-1alpha, and hypoxia-inducible factor-1alpha. The changes
      induced by GD IgG were partially abrogated by A2aR small interfering RNA and an
      A2aR antagonist. These results were supported by data on the goiter samples from
      the thyrotropin receptor adenovirus-induced GD mouse model (female). These data
      demonstrate that GD IgG could up-regulate the VEGF expression through A2aR,
      indicating a potential mechanism for goitrogenesis in GD. 

PMID- 24080367
TI  - Loss of 5alpha-reductase type 1 accelerates the development of hepatic steatosis
      but protects against hepatocellular carcinoma in male mice.
AB  - Nonalcoholic fatty liver disease (NAFLD) has been associated with glucocorticoid
      excess and androgen deficiency, yet in the majority of patients with
      steatohepatitis, circulating cortisol and androgen levels are normal. The enzyme
      5alpha-reductase (5alphaR) has a critical role in androgen and glucocorticoid
      action. We hypothesize that 5alphaR has an important role in the pathogenesis of
      steatohepatitis through regulation of intracrine/paracrine hormone availability.
      Human liver samples from patients with NAFLD and normal donor tissue were used
      for gene expression and immunohistochemical analysis. NAFLD samples were scored
      using the Kleiner classification. In addition, 5alphaR1(-/-), 5alphaR2(-/-), and
      wild-type (WT) mice were fed normal chow or American lifestyle-induced obesity
      syndrome (ALIOS) diet for 6 or 12 months. Liver histology was graded and staged.
      Hepatic and circulating free fatty acid and triglyceride levels were quantified,
      and gene and protein expression was measured by real-time PCR and
      immunohistochemistry. 5alphaR1 and -2 were highly expressed in human liver, and
      5alphaR1 protein expression increased with severity of NAFLD. 5alphaR1(-/-) (but
      not 5alphaR2(-/-)) mice fed an ALIOS diet developed greater hepatic steatosis
      than WT mice, and hepatic mRNA expression of genes involved in insulin signaling
      was decreased. Furthermore, 60% of WT mice developed focal hepatocellular lesions
      consistent with hepatocellular carcinoma after 12 months of the ALIOS diet,
      compared with 20% of 5alphaR2(-/-) and 0% of 5alphaR1(-/-) mice (P < .05).
      5alphaR1 deletion accelerates the development of hepatic steatosis but may
      protect against the development of NAFLD-related hepatocellular neoplasia and
      therefore has potential as a therapeutic target. 

PMID- 24080370
TI  - Going out on a limb for a difficult diagnosis: a case report.
AB  - Sacral tumors with fetiform features are rare and pose a diagnostic challenge to
      the ultrasonologist. Sacrococcygeal teratomas (SCT) and parasitic twins can have
      very similar sonographic features but have different implications to an affected
      pregnancy. While postnatal histopathology is ultimately necessary to distinguish
      between a SCT and a heteropagus twin, certain characteristics, such as the
      presence of a vertebral column and the pattern and rate of tumor growth, may be
      useful to guide counseling and management decisions. 

PMID- 24080369
TI  - Mechanical behavior of fixation components for periprosthetic fracture surgery.
AB  - BACKGROUND: Reliable periprosthetic fracture treatment needs detailed knowledge
      on the mechanical behavior of the fixation components used. The holding capacity
      of three conventional fixation components for periprosthetic fracture treatment
      was systematically investigated under different loading directions. METHODS:
      Locking compression plates were fixed to a 7 cm long part of diaphyseal fresh
      frozen human femur with either a single 1.7 mm cerclage cable, a 5.0mm
      monocortical or a bicortical locking screw (n=5 per group). Constructs were
      loaded in lateral, torsional and axial direction with respect to the bone axis in
      a load-to-failure test. Corresponding stress distribution around the screw holes
      was analyzed by finite element modeling. FINDINGS: Both screw fixations revealed
      significantly higher stiffness and ultimate strength in axial compression and
      torsion compared to the cerclage (all P<0.01). Ultimate strength in lateral
      loading and torsion was significantly higher for bicortical screws (mean 3968 N
      SD 657; mean 28.8 Nm SD 5.9) compared to monocortical screws (mean 2748 N SD 585;
      mean 14.4 Nm SD 5.7 Nm) and cerclages (mean 3001N SD 252; mean 3.2 Nm SD 2.0)
      (P<=0.04). Stress distribution around the screw hole varied according to the
      screw type and load direction. INTERPRETATION: Fixation components may be
      combined according to their individual advantages to achieve an optimal
      periprosthetic fracture fixation.

PMID- 24080371
TI  - CT of acute appendicitis: can diagnostic accuracy serve as a practical
      performance metric for readers specialized in abdominal imaging?
AB  - PURPOSE: To investigate diagnostic accuracy for acute appendicitis at computed
      tomography (CT) as a performance metric for radiologists specialized in abdominal
      imaging. MATERIALS AND METHODS: We retrospectively identified six attending
      abdominal imagers who each independently interpreted over 100 CT studies for
      suspected acute appendicitis. RESULTS: The mean number of studies per reader was
      311 (range, 129-386). Mean reader diagnostic accuracy was 95.0% (range, 91.4
      97.1%). Only one had a diagnostic accuracy (91.4%) that was significantly lower
      than all others. CONCLUSION: Diagnostic accuracy for acute appendicitis at CT may
      be an impractical performance metric for radiologists specialized in abdominal
      imaging.

PMID- 24080372
TI  - Activation of the human mirror neuron system during the observation of the
      manipulation of virtual tools in the absence of a visible effector limb.
AB  - This work explores the mirror neuron system activity produced by the observation
      of virtual tool manipulations in the absence of a visible effector limb.
      Functional MRI data was obtained from healthy right-handed participants who
      manipulated a virtual paddle in the context of a digital game and watched replays
      of their actions. The results show how action observation produced extended
      bilateral activations in the parietofrontal mirror neuron system. At the same
      time, three regions in the left hemisphere (in the primary motor and the primary
      somatosensory cortex, the supplementary motor area and the dorsolateral
      prefrontal cortex) showed a reduced BOLD, possibly related with the prevention of
      inappropriate motor execution. These results can be of interest for researchers
      and developers working in the field of action observation neurorehabilitation. 

PMID- 24080373
TI  - Restoring ionotropic inhibition as an analgesic strategy.
AB  - Neuronal inhibition in nociceptive relays of the spinal cord is essential for the
      proper processing of nociceptive information. In the spinal cord dorsal horn, the
      activity of synaptic and extrasynaptic GABAA and glycine receptors generates
      rapid, Cl(-)-dependent neuronal inhibition. A loss of this ionotropic inhibition,
      particularly through the collapse of the inhibitory Cl(-)-gradient, is a key
      mechanism by which pathological pain conditions develop. This review summarizes
      the roles of ionotropic inhibition in the regulation of nociception, and explores
      recent evidence that the potentiation of GABAA or glycine receptor activity or
      the enhancement of inhibitory drive can reverse pathological pain.

PMID- 24080374
TI  - Bidirectional regulation of P body formation mediated by eIF4F complex formation
      in sensory neurons.
AB  - Processing (P) bodies are RNA granules that comprise key cellular sites for the
      metabolism of mRNAs. In certain cells, including neurons, these RNA granules may
      also play an important role in storage of mRNAs in a translationally dormant
      state. Utilizing nerve growth factor (NGF) and interleukin 6 (IL6), which
      stimulate cap-dependent translation in sensory neurons, and adenosine
      monophosphate activated protein kinase (AMPK) activators, which inhibit cap
      dependent translation, we have tested the hypothesis that cap-dependent
      translation is linked to P body formation in mammalian sensory neurons. Treatment
      with NGF and IL6 decreases, whereas metformin increases biochemical association
      of the P body marker and translational repressor/decapping activator Rck/p54/dhh1
      with the 5'-mRNA-cap suggesting an ordered assembly of P bodies. Likewise,
      diverse AMPK activators enhance P body formation while NGF and IL6 decrease P
      bodies in sensory neurons. This bidirectional P body plasticity readily occurs in
      the axonal compartment of these neurons. These studies indicate that P body
      formation is intricately linked to cap-dependent translation in mammalian sensory
      neurons suggesting an important role for these organelles in the regulation of
      mRNA metabolism in the adult PNS. 

PMID- 24080375
TI  - Dynamic cortical involvement in implicit anticipation during statistical
      learning.
AB  - The prediction of future events is fundamental in a large number of critical
      neurobehavioral contexts including implicit motor learning. This learning process
      relies on the probabilities with which events occur, and is a dynamic phenomenon.
      The aim of present study was to investigate the development of anticipatory
      processes during implicit learning. A decision making task was employed in which
      the frequency of trial types was manipulated such that one trial type was
      disproportionately prevalent as compared to the remaining three trial types. A
      275 channel whole-head magnetoencephalography (MEG) system was used to
      investigate the spatiotemporal distribution of event-related desynchronization
      (ERD) and synchronization (ERS). The results revealed that oscillations within
      the alpha (10-12 Hz) and beta (14-30 Hz) frequencies were associated with
      anticipatory processes in distinct networks in the course of learning. During
      early phases of learning the contralateral motor cortex, the anterior cingulate,
      the caudate and the inferior frontal gyrus showed ERDs within beta and alpha
      frequencies, putatively reflecting preparation of next motor response. As the
      task progressed, alpha ERSs in occipitotemporal regions and putamen likely
      reflect perceptual anticipation of the forthcoming stimuli.

PMID- 24080376
TI  - Thymoquinone protects cultured hippocampal and human induced pluripotent stem
      cells-derived neurons against alpha-synuclein-induced synapse damage.
AB  - The seeds of Nigella sativa are used worldwide to treat various diseases and
      ailments. Thymoquinone (TQ) that is present in the essential oil of these seeds
      mediates most of the plant's diverse therapeutic effects. The present study aimed
      to determine whether TQ protects against alpha-synuclein (alphaSN)-induced
      synaptic toxicity in rat hippocampal and human induced pluripotent stem cell
      (hiPSC)-derived neurons. Here, we report that alphaSN decreased the level of
      synaptophysin, a protein used as an indicator of synaptic density, in cultured
      hippocampal and hiPSC-derived neurons. However, simultaneous treatment with
      alphaSN and TQ protected neurons against alphaSN-induced synapse damage, as
      revealed by immunostaining. Moreover, administration of TQ efficiently induced
      protection in these cells against alphaSN-induced inhibition of synaptic vesicle
      recycling in hippocampal and hiPSC-derived neurons as well as against mutated
      P123H beta-synuclein (betaSN) in hippocampal neurons, as revealed by experiments
      using the fluorescent dye FM1-43. Using a multielectrode array, we further
      demonstrated that the treatment of hiPSC-derived neurons with alphaSN induced a
      reduction in spontaneous firing activity, and cotreatment with alphaSN and TQ
      partially reversed this loss. These results suggest that TQ protects cultured rat
      primary hippocampal and hiPSC-derived neurons against alphaSN-induced synaptic
      toxicity and could be a promising therapeutic agent for patients with Parkinson's
      disease and dementia with Lewy bodies. 

PMID- 24080377
TI  - REM sleep deprivation increases the expression of interleukin genes in mice
      hypothalamus.
AB  - Recently, evidence has suggested the possible involvement of inflammatory
      cytokines in sleep deprivation (SD). In this study, we assessed the patterns of
      inflammatory gene regulation in the hypothalamus of REM SD mice. C57BL/6 mice
      were randomly assigned to two groups, SD (n=15) and control groups (n=15). Mice
      in the SD group were sleep-deprived for 72h using modified multiple platforms.
      Microarray analysis on inflammatory genes was performed in mice hypothalamus. In
      addition, interleukin 1 beta (IL1beta) protein expression was analyzed by the
      immunochemistry method. Through microarray analysis, we found that expressions of
      IL subfamily genes, such as IL1beta (2.55-fold), IL18 (1.92-fold), IL11 receptor
      alpha chain 1 (1.48-fold), IL5 (1.41-fold), and IL17E genes (1.31-fold), were up
      regulated in the hypothalamus of SD mice compared to the control. The increase in
      the expression of these genes was also confirmed by RT-PCR. Among these genes,
      the expression of IL1beta was particularly increased in the hypothalamus of SD
      mice. Interestingly, we found that the protein expression of endogenous IL1beta
      was also elevated in the hypothalamus of SD mice compared to the control mice.
      These results implicate that IL subfamily genes, and in particular, IL1beta, may
      play a role in sleep regulation in the hypothalamus of REM SD mice. 

PMID- 24080378
TI  - Property evolution during vitrification of dimethacrylate photopolymer networks.
AB  - OBJECTIVES: This study seeks to correlate the interrelated properties of
      conversion, shrinkage, modulus and stress as dimethacrylate networks transition
      from rubbery to glassy states during photopolymerization. METHODS: An unfilled
      BisGMA/TEGDMA resin was photocured for various irradiation intervals (7-600 s) to
      provide controlled levels of immediate conversion, which was monitored
      continuously for 10 min. Fiber optic near-infrared spectroscopy permitted
      coupling of real-time conversion measurement with dynamic polymerization
      shrinkage (linometer), modulus (dynamic mechanical analyzer) and stress
      (tensometer) development profiles. RESULTS: The varied irradiation conditions
      produced final conversion ranging from 6% to more than 60%. Post-irradiation
      conversion (dark cure) was quite limited when photopolymerization was interrupted
      either at very low or very high levels of conversion while significant dark cure
      contributions were possible for photocuring reactions suspended within the post
      gel, rubbery regime. Analysis of conversion-based property evolution during and
      subsequent to photocuring demonstrated that the shrinkage rate increased
      significantly at about 40% conversion followed by late-stage suppression in the
      conversion-dependent shrinkage rate that begins at about 45-50% conversion. The
      gradual vitrification process over this conversion range is evident based on the
      broad but well-defined inflection in the modulus versus conversion data. As
      limiting conversion is approached, modulus and, to a somewhat lesser extent,
      stress rise precipitously as a result of vitrification with the stress profile
      showing little if any late-stage suppression as seen with shrinkage.
      SIGNIFICANCE: Near the limiting conversion for this model resin, the volumetric
      polymerization shrinkage rate slows while an exponential rise in modulus promotes
      the vitrification process that appears to largely dictate stress development.

PMID- 24080379
TI  - Safety and efficacy of device closure for patent foramen ovale for secondary
      prevention of neurological events: Comprehensive systematic review and meta
      analysis of randomized controlled trials.
AB  - BACKGROUND: Controversy persists regarding the management of patients with
      cryptogenic stroke and patent foramen ovale (PFO). We performed a meta-analysis
      of randomized controlled trials comparing PFO closure with medical therapy.
      METHODS AND RESULTS: A prospective protocol was developed and registered using
      the following data sources: PubMed, Cochrane Register of Controlled Trials,
      conference proceedings, and Internet-based resources of clinical trials. Primary
      analyses were performed using the intention-to-treat method. Three randomized
      trials comparing percutaneous PFO closure vs. medical therapy for secondary
      prevention of embolic neurological events formed the data set. Baseline
      characteristics were similar. During long-term follow-up, the pooled incidence of
      the primary endpoint (composite of stroke, death, or fatal stroke) was 3.4% in
      the PFO closure arm and 4.8% in the medical therapy group [risk-reduction (RR)
      0.7 (0.48-1.06); p=0.09]. The incidence of recurrent neurological events
      (secondary endpoint) was 1.7% for PFO closure and 2.7% for medical therapy [RR
      0.66 (0.35-1.24), p=0.19]. There was no difference in terms of death or adverse
      events between the two groups. CONCLUSIONS: While this meta-analysis of
      randomized clinical trials demonstrated no statistical significance in comparison
      to medical therapy, there was a trend towards overall improvement in outcomes in
      the PFO closure group.

PMID- 24080380
TI  - Enhancing the biophysical properties of mRFP1 through incorporation of
      fluoroproline.
AB  - Here we enhanced the stability and biophysical properties of mRFP1 through a
      combination of canonical and non-canonical amino acid mutagenesis. The global
      replacement of proline residue with (2S, 4R)-4-fluoroproline [(4R)-FP] into mRFP1
      led to soluble protein but lost its fluorescence, whereas (2S, 4S)-4
      fluoroproline [(4S)-FP] incorporation resulted in insoluble protein. The
      bioinformatics analysis revealed that (4R)-FP incorporation at Pro63 caused
      fluorescence loss due to the steric hindrance of fluorine atom of (4R)-FP with
      the chromophore. Therefore, Pro63 residue was mutated with the smallest amino
      acid Ala to maintain non coplanar conformation of the chromophore and helps to
      retain its fluorescence with (4R)-FP incorporation. The incorporation of (4R)-FP
      into mRFP1-P63A showed about 2-3-fold enhancement in thermal and chemical
      stability. The rate of maturation is also greatly accelerated over the presence
      of (4R)-FP into mRFP1-P63A. Our study showed that a successful enhancement in the
      biophysical property of mRFP1-P63A[(4R)-FP] using non-canonical amino acid
      mutagenesis after mutating non-permissive site Pro63 into Ala. 

PMID- 24080381
TI  - Accelerating plant breeding.
AB  - The growing demand for food with limited arable land available necessitates that
      the yield of major food crops continues to increase over time. Advances in marker
      technology, predictive statistics, and breeding methodology have allowed for
      continued increases in crop performance through genetic improvement. However, one
      major bottleneck is the generation time of plants, which is biologically limited
      and has not been improved since the introduction of doubled haploid technology.
      In this opinion article, we propose to implement in vitro nurseries, which could
      substantially shorten generation time through rapid cycles of meiosis and
      mitosis. This could prove a useful tool for speeding up future breeding programs
      with the aim of sustainable food production. 

PMID- 24080383
TI  - Abnormal level of arousal as a predictor of delirium and inattention: an
      exploratory study.
AB  - OBJECTIVE: Abnormal level of arousal (LoA) and inattention are key features of
      delirium. However, the extent to which abnormal LoA alone might predict delirium
      and inattention is unclear. Here we tested the hypotheses that (1) patients with
      abnormal LoA have delirium, and (2) abnormal LoA is associated with worse
      performance on tests of attention. METHODS: Thirty acute hip fracture patients
      aged 64-97 years underwent assessments of LoA, delirium status, and attentional
      functioning in the 24 hours before surgery and at 2-4 and 7-10 days after
      surgery. The Observational Scale of Level of Arousal (OSLA) and the Richmond
      Agitation-Sedation Scale (RASS) were used to assess LoA. Sustained attention was
      measured with the Edinburgh Delirium Test Box. Delirium was assessed with the
      Confusion Assessment Method and the Delirium Rating Scale-Revised-98. RESULTS:
      Ten patients (33%) were diagnosed with delirium. Abnormal LoA as measured by the
      OSLA was strongly associated with the presence of delirium. The area under the
      receiver operating characteristic curve was 0.89 (95% confidence interval: 0.81
      0.97), with a sensitivity of 0.87 and a specificity of 0.81. Area under the
      curve, sensitivity, and specificity for the RASS were 0.81 (95% confidence
      interval: 0.68-0.94), 0.80, and 0.79, respectively. Abnormal LoA was associated
      with worse attentional deficits preoperatively and at postoperative days 2-4 (p
      <0.01). CONCLUSION: These exploratory findings suggest that abnormal LoA is a
      strong indicator of delirium. Also, abnormal LoA is strongly associated with
      inattention as measured by an objective cognitive test. These findings suggest
      that acute-onset abnormal LoA could be used as a trigger for delirium assessment
      in routine clinical practice. Future work will help to clarify further the
      interrelationships among abnormal LoA, inattention, and delirium.

PMID- 24080382
TI  - In vivo quantification of white matter microstructure for use in aging: a focus
      on two emerging techniques.
AB  - Human brain imaging has seen many advances in the quantification of white matter
      in vivo. For example, these advances have revealed the association between white
      matter damage and vascular disease as well as their impact on risk for and
      development of dementia and depression in an aging population. Current
      neuroimaging methods to quantify white matter damage provide a foundation for
      understanding such age-related neuropathology; however, these methods are not as
      adept at determining the underlying microstructural abnormalities signaling at
      risk tissue or driving white matter damage in the aging brain. This review will
      begin with a brief overview of the use of diffusion tensor imaging (DTI) in
      understanding white matter alterations in aging before focusing in more detail on
      select advances in both diffusion-based methods and multi-component relaxometry
      techniques for imaging white matter microstructural integrity within myelin
      sheaths and the axons they encase. Although DTI greatly extended the field of
      white matter interrogation, these more recent technological advances will add
      clarity to the underlying microstructural mechanisms that contribute to white
      matter damage. More specifically, the methods highlighted in this review may
      prove more sensitive (and specific) for determining the contribution of myelin
      versus axonal integrity to the aging of white matter in brain. 

PMID- 24080384
TI  - Pre-clinical cognitive phenotypes for Alzheimer disease: a latent profile
      approach.
AB  - BACKGROUND: Cognitive profiles for pre-clinical Alzheimer disease (AD) can be
      used to identify groups of individuals at risk for disease and better
      characterize pre-clinical disease. Profiles or patterns of performance as pre
      clinical phenotypes may be more useful than individual test scores or measures of
      global decline. OBJECTIVE: To evaluate patterns of cognitive performance in
      cognitively normal individuals to derive latent profiles associated with later
      onset of disease using a combination of factor analysis and latent profile
      analysis. METHODS: The National Alzheimer Coordinating Centers collect data,
      including a battery of neuropsychological tests, from participants at 29 National
      Institute on Aging-funded Alzheimer Disease Centers across the United States.
      Prior factor analyses of this battery demonstrated a four-factor structure
      comprising memory, attention, language, and executive function. Factor scores
      from these analyses were used in a latent profile approach to characterize
      cognition among a group of cognitively normal participants (N = 3,911).
      Associations between latent profiles and disease outcomes an average of 3 years
      later were evaluated with multinomial regression models. Similar analyses were
      used to determine predictors of profile membership. RESULTS: Four groups were
      identified; each with distinct characteristics and significantly associated with
      later disease outcomes. Two groups were significantly associated with development
      of cognitive impairment. In post hoc analyses, both the Trail Making Test Part B,
      and a contrast score (Delayed Recall - Trails B), significantly predicted group
      membership and later cognitive impairment. CONCLUSIONS: Latent profile analysis
      is a useful method to evaluate patterns of cognition in large samples for the
      identification of preclinical AD phenotypes; comparable results, however, can be
      achieved with very sensitive tests and contrast scores.

PMID- 24080385
TI  - The moderating effect of age on the 12-month prevalence of anxiety and depressive
      disorders in adults with a lifetime history of cancer.
AB  - OBJECTIVE: To determine how age may modulate the association of a history of
      cancer with a 12-month history of anxiety and depressive disorders. METHODS: The
      authors used population-based, cross-sectional surveys, the Collaborative
      Psychiatric Epidemiology Surveys. These surveys were conducted in the United
      States in 2001-2003 and included 16,423 adult participants, of whom 702 reported
      a cancer history. The Composite International Diagnostic Interview evaluated the
      presence of a 12-month history of anxiety and depressive disorders. RESULTS:
      Among those with a cancer history, older adults (>=60 years old) were less likely
      than younger adults (18-59 years old) to have a 12-month history of an anxiety or
      depressive disorder. Compared with their peers without cancer, younger adults
      with a cancer history had more anxiety (23.8% versus 13.9%) and depressive (16.0%
      versus 9.5%) disorders, whereas older adults with a cancer history had lower
      levels of anxiety (3.7% versus 6.3%) and depressive (1.9% versus 3.9%) disorders.
      In multivariable modeling, there was a statistically significant interaction
      between age group and cancer history, with the risk for anxiety and depressive
      disorders elevated in the younger age group with a cancer history (odds ratio:
      5.84 and odds ratio: 6.13, respectively) but decreased in the older age group
      with a cancer history (odds ratio: 0.55 and odds ratio: 0.45, respectively).
      CONCLUSION: The authors' findings suggest a considerable age-dependent variation
      with regard to anxiety and depressive disorders in adults with a cancer history.
      Investigation of the mechanisms contributing to this apparent age differential in
      risk could have important mental illness treatment implications in this
      population.

PMID- 24080386
TI  - Protection of dried probiotic bacteria from bile using bile adsorbent resins.
AB  - Enteric coated oral tablets or capsules can deliver dried live cells directly
      into the intestine. Previously, we found that a live attenuated bacterial vaccine
      acquired sensitivity to intestinal bile when dried, raising the possibility that
      although gastric acid can be bypassed, significant loss of viability might occur
      on release from an enteric coated oral formulations. Here we demonstrate that
      some food-grade lyophilised preparations of Lactobacillus casei and Lactobacillus
      salivarius also show temporary bile sensitivity that can be rapidly reversed by
      rehydration. To protect dried bacterial cells from temporary bile sensitivity, we
      propose using bile acid adsorbing resins, such as cholestyramine, which are bile
      acid binding agents, historically used to lower cholesterol levels. VcapsTM HPMC
      capsules alone provided up to 830-fold protection from bile. The inclusion of 50%
      w/w cholestyramine in VcapsTM HPMC capsules resulted in release of up to 1700
      fold more live Lactobacillus casei into simulated intestinal fluid containing 1%
      bile, when compared to dried cells added directly to bile. We conclude that
      delivery of dried live probiotic organisms to the intestine may be improved by
      providing protection from bile by addition of bile adsorbing resins and the use
      of HPMC capsules.

PMID- 24080387
TI  - Insights into cellulosome assembly and dynamics: from dissection to
      reconstruction of the supramolecular enzyme complex.
AB  - Cellulosomes are multi-enzyme complexes produced by anaerobic bacteria for the
      efficient deconstruction of plant cell wall polysaccharides. The assembly of
      enzymatic subunits onto a central non-catalytic scaffoldin subunit is mediated by
      a highly specific interaction between the enzyme-bearing dockerin modules and the
      resident cohesin modules of the scaffoldin, which affords their catalytic
      activities to work synergistically. The scaffoldin also imparts substrate-binding
      and bacterial-anchoring properties, the latter of which involves a second cohesin
      dockerin interaction. Recent structure-function studies reveal an ever-growing
      array of unique and increasingly complex cohesin-dockerin complexes and
      cellulosomal enzymes with novel activities. A 'build' approach involving
      multimodular cellulosomal segments has provided a structural model of an
      organized yet conformationally dynamic supramolecular assembly with the potential
      to form higher order structures. 

PMID- 24080388
TI  - Counter-regulation of alpha- and beta-synuclein expression at the transcriptional
      level.
AB  - Alpha-synuclein is a cytosolic protein associated with a range of diseases
      including Parkinson's disease. In these diseases alpha-synuclein aggregates and
      this is believed to play a causative role in disease progression. Alpha-synuclein
      aggregation has been suggested to be caused by increased expression levels and
      has also been suggested to be countered by increased beta-synuclein expression.
      In this regard, strategies to counter-regulate the expression of the synucleins
      by increasing beta-synuclein expression relative to alpha-synuclein may be
      beneficial in preventing disease progression. We therefore studied the regulation
      of alpha-synuclein to try to identify pathways that might counter-regulate the
      synucleins. We identified members of the ZSCAN family of transcription factors as
      specific repressors of alpha-synuclein. In particular ZSCAN21 was found to both
      repress alpha-synuclein and increase beta-synuclein expression. These findings
      support the notion that a single pathway in the cell can counter-regulate the
      expression of the synucleins. Support for this came from experiments that showed
      that ZSCAN21 expression decreases alpha-synuclein aggregation in the cells. 

PMID- 24080389
TI  - Longitudinal follow-up of ventricular performance in healthy neonates.
AB  - BACKGROUND: Specific follow-up of newly introduced echocardiographic parameters
      in healthy neonates and infants is limited. AIM: To prospectively describe follow
      up of left ventricular (LV) tissue Doppler imaging (TDI) and speckle tracking
      strain parameters in healthy subjects up to two months after birth. DESIGN: This
      is a longitudinal follow-up study. SUBJECTS: Twenty-eight (10 male) healthy
      newborns were included and underwent transthoracic echocardiography 1-3 days, 3
      weeks and 6-7 weeks after birth. OUTCOME MEASURES: In each echocardiogram,
      parameters describing cardiac growth, including LV mass (LVM), were assessed.
      Additionally, TDI derived peak systolic velocity (S') and peak early (E') and
      late (A') diastolic velocities were assessed in the basal LV free wall and
      interventricular septum (IVS). Finally LV longitudinal, radial and
      circumferential global peak strain parameters were assessed using speckle
      tracking strain imaging. RESULTS: LVM significantly increased during follow-up
      (7.6 +/- 2.4 versus 12.4 +/- 3.2g, p = 0.002). Similarly at 1-3 days versus 6-7
      weeks after birth, an increase in LV and IVS systolic (LV S' 4.1 +/- 1.5 versus
      6.3 +/- 1.5 cm/s, p = 0.001; IVS S' 3.6 +/- 0.9 versus 6.4 +/- 1.3 cm/s, p <
      0.001) and diastolic (LV E' 6.1 +/- 2.2 versus 9.7 +/- 2.9 cm/s, p = 0.002; IVS
      E' 5.1 +/- 1.4 versus 10.7 +/- 3.3 cm/s, p < 0.001) TDI parameters was observed.
      In contrast, global peak longitudinal, radial and circumferential strain
      parameters did not significantly change during follow-up. CONCLUSIONS: A
      significant increase in LV systolic and diastolic TDI parameters was observed up
      to two months after birth. Yet this increase may be (cardiac) growth-dependent.
      No significant changes were observed in speckle tracking strain derived global
      peak strain parameters; this may render the technique particularly valuable in
      evaluation of LV systolic performance during periods of significant growth, such
      as the neonatal period.

PMID- 24080390
TI  - Longitudinal assessment of atrioventricular annulus excursion by grey-scale m
      mode and colour tissue Doppler imaging in premature infants.
AB  - BACKGROUND: There is a lack of standardized echocardiographic parameters to
      quantify ventricular function in newborn infants. Long-axis systolic ventricular
      shortening is a useful parameter of global ventricular function. AIMS: Serial
      assessment of long-axis systolic atrioventricular annulus excursion in premature
      infants. METHODS: Two-centre, prospective observational study. Fifty-seven
      premature infants (26 girls), median (range) gestational age 33(+5) (31(0)
      34(+6)) weeks(+days), birth weight 1925 (1127-2836) grams were included.
      Echocardiographic examinations were performed at the first three days of life and
      at expected term. OUTCOME MEASURES: Systolic annulus excursion by grey-scale m
      mode and colour tissue Doppler imaging (cTDI). RESULTS: A consistent longitudinal
      pattern was found for annulus excursion by grey-scale m-mode and cTDI. All
      parameters showed a pronounced increase at expected term (p < 0.001). After
      normalizing for ventricular size the increase at term was less pronounced.
      Results were lower by cTDI than by grey-scale m-mode for the left and right
      ventricular walls (p < 0.001). Intraobserver variability (range 1.5-9.8%) was
      lower than interobserver variability (5.5-18%). CONCLUSIONS: Serial assessment of
      longitudinal ventricular shortening in premature infants by grey-scale m-mode and
      cTDI was feasible and the measurements displayed a consistent pattern. cTDI
      excursion measurements were lower and more dependent on image quality than m-mode
      measurements. Lower intraobserver variability suggests that repeated measurements
      should preferably be performed by the same observer. Annulus excursion varies
      with ventricular size and we suggest normalizing measurements by ventricular
      size.

PMID- 24080391
TI  - Suboptimal maternal nutrition affects offspring health in adult life.
AB  - Suboptimal maternal nutrition during pregnancy is prevalent and compromises fetal
      development. Physiological and metabolic adaptations made by the fetus to an
      inadequate, or excess, maternal nutritional environment, may promote immediate
      survival but are lasting, conferring significantly increased risks of ill health
      in childhood and adulthood. In addition, such fetal adaptations are particularly
      detrimental when nutrient supply is no longer constrained in contemporary
      nutrient rich environments. Given the prevalence of suboptimal maternal
      nutritional environments during fetal development, effective prevention, early
      detection and therapeutic interventions to reduce the increased risks on
      population health must be a health priority. Therefore, the mechanisms of these
      lasting in utero adaptations are highly relevant to establishing how exposure to
      a suboptimal nutritional environment impacts on the health of current generations
      living in an environment challenged by excess nutrition. 

PMID- 24080392
TI  - Decisions on control of foot-and-mouth disease informed using model predictions.
AB  - The decision on whether or not to change the control strategy, such as
      introducing emergency vaccination, is perhaps one of the most difficult decisions
      faced by the veterinary authorities during a foot-and-mouth disease (FMD)
      epidemic. A simple tool that may predict the epidemic outcome and consequences
      would be useful to assist the veterinary authorities in the decision-making
      process. A previously proposed simple quantitative tool based on the first 14
      days outbreaks (FFO) of FMD was used with results from an FMD simulation
      exercise. Epidemic outcomes included the number of affected herds, epidemic
      duration, geographical size and costs. The first 14 days spatial spread (FFS) was
      also included to further support the prediction. The epidemic data was obtained
      from a Danish version (DTU-DADS) of a pre-existing FMD simulation model (Davis
      Animal Disease Spread - DADS) adapted to model the spread of FMD in Denmark. The
      European Union (EU) and Danish regulations for FMD control were used in the
      simulation. The correlations between FFO and FFS and the additional number of
      affected herds after day 14 following detection of the first infected herd were
      0.66 and 0.82, respectively. The variation explained by the FFO at day 14
      following detection was high (P-value<0.001). This indicates that the FFO may
      take a part in the decision of whether or not to intensify FMD control, for
      instance by introducing emergency vaccination and/or pre-emptive depopulation,
      which might prevent a "catastrophic situation". A significant part of the
      variation was explained by supplementing the model with the FFS (P-value<0.001).
      Furthermore, the type of the index-herd was also a significant predictor of the
      epidemic outcomes (P-value<0.05). The results of the current study suggest that
      national veterinary authorities should consider to model their national situation
      and to use FFO and FFS to help planning and updating their contingency plans and
      FMD emergency control strategies. 

PMID- 24080393
TI  - Removal of pharmaceuticals and personal care products in aquatic plant-based
      systems: a review.
AB  - Pharmaceuticals and personal care products (PPCPs) in the aquatic environment are
      regarded as emerging contaminants and have attracted increasing concern. The use
      of aquatic plant-based systems such as constructed wetlands (CWs) for treatment
      of conventional pollutants has been well documented. However, available research
      studies on aquatic plant-based systems for PPCP removal are still limited. The
      removal of PPCPs in CWs often involves a diverse and complex set of physical,
      chemical and biological processes, which can be affected by the design and
      operational parameters selected for treatment. This review summarizes the PPCP
      removal performance in different aquatic plant-based systems. We also review the
      recent progress made towards a better understanding of the various mechanisms and
      pathways of PPCP attenuation during such phytoremediation. Additionally, the
      effect of key CW design characteristics and their interaction with the physico
      chemical parameters that may influence the removal of PPCPs in functioning
      aquatic plant-based systems is discussed. 

PMID- 24080394
TI  - Effects of PEG-induced osmotic stress on growth and dhurrin levels of forage
      sorghum.
AB  - Sorghum (Sorghum bicolor L. Moench) is a valuable forage crop in regions with low
      soil moisture. Sorghum may accumulate high concentrations of the cyanogenic
      glucoside dhurrin when drought stressed resulting in possible cyanide (HCN)
      intoxication of grazing animals. In addition, high concentrations of nitrate,
      also potentially toxic to ruminants, may accumulate during or shortly after
      periods of drought. Little is known about the degree and duration of drought
      stress required to induce dhurrin accumulation, or how changes in dhurrin
      concentration are influenced by plant size or nitrate metabolism. Given that
      finely regulating soil moisture under controlled conditions is notoriously
      difficult, we exposed sorghum plants to varying degrees of osmotic stress by
      growing them for different lengths of time in hydroponic solutions containing
      polyethylene glycol (PEG). Plants grown in medium containing 20% PEG (-0.5 MPa)
      for an extended period had significantly higher concentrations of dhurrin in
      their shoots but lower dhurrin concentrations in their roots. The total amount of
      dhurrin in the shoots of plants from the various treatments was not significantly
      different on a per mass basis, although a greater proportion of shoot N was
      allocated to dhurrin. Following transfer from medium containing 20% PEG to medium
      lacking PEG, shoot dhurrin concentrations decreased but nitrate concentrations
      increased to levels potentially toxic to grazing ruminants. This response is
      likely due to the resumption of plant growth and root activity, increasing the
      rate of nitrate uptake. Data presented in this article support a role for
      cyanogenic glucosides in mitigating oxidative stress. 

PMID- 24080395
TI  - Increasing the starch content and grain weight of common wheat by overexpression
      of the cytosolic AGPase large subunit gene.
AB  - ADP-glucose pyrophosphorylase (AGPase) catalyzes the first committed step of
      starch synthesis. AGPase is a heterotetramer composed of two large subunits and
      two small subunits, has cytosolic and plastidial isoforms, and is detected mainly
      in the cytosol of endosperm in cereal crops. To investigate the effects of AGPase
      cytosolic large subunit gene (LSU I) on starch biosynthesis in higher plant, in
      this study, a TaLSU I gene from wheat was overexpressed under the control of an
      endosperm-specific promoter in a wheat cultivar (Yumai 34). PCR, Southern blot,
      and real-time RT-PCR analyses indicated that the transgene was integrated into
      the genome of transgenic plants and was overexpressed in their progeny. The
      overexpression of the TaLSU I gene remarkably enhanced AGPase activity, endosperm
      starch weight, grain number per spike, and single grain weight. Therefore, we
      conclude that overexpression of the TaLSU I gene enhances the starch biosynthesis
      in endosperm of wheat grains, having potential applications in wheat breeding to
      develop a high-yield wheat cultivar with high starch weight and kernel weight. 

PMID- 24080396
TI  - Drought and salt tolerance enhancement of transgenic Arabidopsis by
      overexpression of the vacuolar pyrophosphatase 1 (EVP1) gene from Eucalyptus
      globulus.
AB  - Vacuolar solute accumulation has been shown to be a mechanism by which plants are
      capable of increasing drought and salt tolerance. The exposure of plants to NaCl
      induces H+ transport into the vacuole by specialized pumps. One of them
      corresponds to the vacuolar H+-pyrophosphatase, which generates a H+ gradient
      across the vacuolar membrane. In our laboratory we isolated the first cDNA
      sequence of a vacuolar pyrophosphatase type I (EVP1) from Eucalyptus globulus.
      Using real-time PCR we confirmed that EVP1 participates in Eucalyptus plants'
      response to drought and salt stress through an ABA independent pathway.
      Additionally, the overexpression of EVP1 in transgenic Arabidopsis resulted in an
      enhancement of drought and salt tolerance. Interestingly we established that the
      transgenic plants had a higher number of root hairs, which may have a positive
      effect on the plant's response to drought and salt stress. These results suggest
      that EVP1 plays an active role in abiotic stress tolerance in E. globulus, and
      that it may be potentially used to enhance drought and stress tolerance of
      plants.

PMID- 24080397
TI  - Harzianolide, a novel plant growth regulator and systemic resistance elicitor
      from Trichoderma harzianum.
AB  - A detailed understanding of the effect of natural products on plant growth and
      protection will underpin new product development for plant production. The
      isolation and characterization of a known secondary metabolite named harzianolide
      from Trichoderma harzianum strain SQR-T037 were described, and the bioactivity of
      the purified compound as well as the crude metabolite extract in plant growth
      promotion and systemic resistance induction was investigated in this study. The
      results showed that harzianolide significantly promoted tomato seedling growth by
      up to 2.5-fold (dry weight) at a concentration of 0.1 ppm compared with the
      control. The result of root scan suggested that Trichoderma secondary metabolites
      may influence the early stages of plant growth through better root development
      for the enhancement of root length and tips. Both of the purified harzianolide
      and crude metabolite extract increased the activity of some defense-related
      enzymes to response to oxidative stress. Examination of six defense-related gene
      expression by real-time reverse transcription-PCR analysis revealed that
      harzianolide induces the expression of genes involved in the salicylic acid (PR1
      and GLU) and jasmonate/ethylene (JERF3) signaling pathways while crude metabolite
      extract inhibited some gene expression (CHI-II and PGIP) related to basal defense
      in tomato plants. Further experiment showed that a subsequent challenge of
      harzianolide-pretreated plants with the pathogen Sclerotinia sclerotiorum
      resulted in higher systemic resistance by the reduction of lesion size. These
      results indicate that secondary metabolites of Trichoderma spp., like
      harzianolide, may play a novel role in both plant growth regulation and plant
      defense responses. 

PMID- 24080398
TI  - Overexpression of a maize E3 ubiquitin ligase gene enhances drought tolerance
      through regulating stomatal aperture and antioxidant system in transgenic
      tobacco.
AB  - Drought is one of the most important limiting factors in crop production. In our
      previous study, a putative Arabidopsis thaliana SALT- AND DROUGHT-INDUCED RING
      FINGER1 (AtSDIR1) homolog encoding a RING-finger protein from Zea mays (ZmRFP1)
      was cloned and its expression pattern and Ub E3 ligase activity were
      characterized. However, it is uncertain that ZmRFP1 acts as a positive regulator
      during drought stress. In this study, we further characterized ZmRFP1 in
      transgenic tobacco to investigate drought tolerance and possible function
      mechanisms. Overexpression of ZmRFP1 enhanced drought tolerance in tobacco. The
      transgenic tobacco lines had more closed stomatal pores, higher proline
      accumulation, but lower levels of malondialdehyde (MDA) when compared with the
      wild type (WT) under drought stress. Further investigation showed that ZmRFP1
      transgenic plants displayed higher SOD and CAT activities, increased NtSOD and
      NtCAT transcript levels, and decreased reactive oxygen species (ROS) accumulation
      under drought stress. Taken together, our results demonstrate that ZmRFP1 confers
      drought stress tolerance in transgenic tobacco not only by increasing the ability
      to retain water, but also by reducing ROS accumulation and membrane damage
      through enhancing the antioxidant system. ZmRFP1 might serve as a candidate gene
      in genetic improvement for drought tolerance engineering in cereal crop plants. 

PMID- 24080399
TI  - Effects of stimulation of glutamate receptors in medial septum on some immune
      responses in rats.
AB  - The immunomodulatory role of medial septum (MS) has been explored so far only in
      MS lesioned rats. But in MS lesioned rats, all the nerve cells and fibres of the
      lesioned area are damaged and the specific role of the neural circuits of MS on
      immunomodulation cannot be assessed from the lesion of MS. Considering the
      presence of a large number of glutamate receptors in MS, the specific role of
      glutamate receptors stimulation on some immune responses has been investigated in
      the present study. Hyperreactive behaviour, TC and DC of WBC, phagocytic activity
      of peripheral leukocytes, adhesibility and cytotoxicity of splenic mononuclear
      cells (MNC), delayed type of hypersensitivity (DTH) responses and the serum
      corticosterone (CORT) were measured after microinfusion of glutamate into MS of
      rats. To ascertain the specific role of those glutamate receptors, the parameters
      were also measured after microinfusion of glutamate receptor blocker 6, 7
      dinitroquinoxaline-2, 3-dione (DNQX). The hyperreactive behaviour, TC and DC of
      WBC remained unaltered after stimulation or blocking of glutamate receptors. The
      phagocytic activity, adhesibility and cytotoxicity of splenic MNC, and DTH
      responses were increased after infusion of 0.25 and 0.5uM glutamate. But after
      infusion of higher dose of glutamate (1uM), the phagocytic activity and the
      adhesibility of splenic MNC were decreased and other parameters remained
      unaltered in that condition. After infusion of 4 and 8mM DNQX all the observed
      immunological parameters were decreased. The CORT concentration was decreased
      after infusion of 0.25 and 0.5uM of glutamate but it was increased after infusion
      of 1uM glutamate or 4 and 8mM DNQX. Results indicate that the medial septal
      glutamate receptors play an important role in the modulation of some immune
      responses. 

PMID- 24080400
TI  - The neural pathway underlying a numerical working memory task in abacus-trained
      children and associated functional connectivity in the resting brain.
AB  - Training can induce significant changes in brain functioning and behavioral
      performance. One consequence of training is changing the pattern of brain
      activation. Abacus training is of interest because abacus experts gain the
      ability to handle digits with unusual speed and accuracy. However, the neural
      correlates of numerical memory in abacus-trained children remain unknown. In the
      current study, we aimed to detect a training effect of abacus-based mental
      calculations on numerical working memory in children. We measured brain
      functional magnetic resonance imaging (fMRI) activation patterns in 17 abacus
      trained children and 17 control children as they performed two numerical working
      memory tasks (digits and beads). Functional MRI results revealed higher
      activation in abacus-trained children than in the controls in the right posterior
      superior parietal lobule/superior occipital gyrus (PSPL/SOG) and the right
      supplementary motor area (SMA) in both tasks. When these regions were used as
      seeds in a functional connectivity analysis of the resting brain, the abacus
      trained children showed significantly enhanced integration between the right SMA
      and the right inferior frontal gyrus (IFG). The IFG is considered to be the key
      region for the control of attention. These findings demonstrate that extensive
      engagement of the fronto-parietal network occurs during numerical memory tasks in
      the abacus-trained group. Furthermore, abacus training may increase the
      functional integration of visuospatial-attention circuitry, which and thus
      enhances high-level cognitive process. 

PMID- 24080402
TI  - Bright illumination reduces parietal EEG alpha activity during a sustained
      attention task.
AB  - The influence of the illumination condition on our cognitive-performance seems to
      be more critical in the modern life, wherein, most people work in an office under
      a specific illumination condition. However, neurophysiological changes in a
      specific illumination state and their cognitive interpretation still remain
      unclear. Thereby, in the present study, the effect of different illumination
      conditions on the same cognitive performance was evaluated particularly by EEG
      wavelet analyses. During a sustained attention task, we observed that the higher
      illumination condition yielded significantly lower parietal tonic
      electroencephalogram (EEG) alpha activity before the presentation of the probe
      digit and longer reaction times, than that of the other illumination conditions.
      Although previous studies suggest that lower prestimulus EEG alpha activity is
      related to higher performance in an upcoming task, the reduced prestimulus alpha
      activity under higher illumination was associated with delayed reaction times in
      the present study. Presumably, the higher background illumination condition seems
      to be too bright for normal attentional processing and distracted participants'
      attention during a sustained attention task. Such a bottom-up effect by stimulus
      salience seemed to overwhelm a prestimulus top-down effect reflected in
      prestimulus alpha power during the bright background condition. This finding
      might imply a dynamic competition between prestimulus top-down and poststimulus
      bottom-up processes. Our findings provide compelling evidence that the
      illumination condition substantially modulates our attentional processing.
      Further refinement of the illumination parameters and subsequent exploration of
      cognitive-modulation are necessary to facilitate our cognitive performance. 

PMID- 24080401
TI  - Postnatal development of glycine receptor subunits alpha1, alpha2, alpha3, and
      beta immunoreactivity in multiple brain stem respiratory-related nuclear groups
      of the rat.
AB  - The respiratory system is immature at birth and significant development occurs
      postnatally. A critical period of respiratory development occurs in rats around
      postnatal days 12-13, when enhanced inhibition dominates over suppressed
      excitation. The mechanisms underlying the heightened inhibition are not fully
      understood. The present study tested our hypothesis that the inhibition is marked
      by a switch in glycine receptor subunits from neonatal to adult form around the
      critical period. An in-depth immunohistochemical and single neuron optical
      densitometric study was undertaken on four respiratory-related nuclear groups
      (the pre-Botzinger complex, nucleus ambiguus, hypoglossal nucleus, and
      ventrolateral subnucleus of solitary tract nucleus), and a non-respiratory
      cuneate nucleus in P2-21 rats. Our data revealed that in the respiratory-related
      nuclear groups: (1) the expressions of GlyRalpha2 and GlyRalpha3 were relatively
      high at P2, but declined after 1-11/2 weeks to their lowest levels at P21; (2)
      the expression of GlyRalpha1 increased with age and reached significance at P12;
      and (3) the expression of GlyRbeta rose from P2 to P12 followed by a slight
      decline until P21. No distinct increase in GlyRalpha1 at P12 was noted in the
      cuneate nucleus. Thus, there is a switch in dominance of expression from neonatal
      GlyRalpha2/alpha3 to the adult GlyRalpha1 and a heightened expression of
      GlyRalpha1 around the critical period in all respiratory-related nuclear groups,
      thereby supporting enhanced inhibition at that time. The rise in the expression
      of GlyRbeta around P12 indicates that it plays an important role in forming the
      mature heteropentameric glycine receptors in these brain stem nuclear groups. 

PMID- 24080403
TI  - Effects of the neurotoxin MPTP and pargyline protection on extracellular energy
      metabolites and dopamine levels in the striatum of freely moving rats.
AB  - The neurotoxin MPTP is known to induce dopamine release and depletion of ATP in
      the striatum of rats. Therefore, we studied the changes induced by MPTP and
      pargyline protection both on striatal dopamine release and on extracellular
      energy metabolites in freely moving rats, using dual asymmetric-flow
      microdialysis. A dual microdialysis probe was inserted in the right striatum of
      rats. MPTP (25mg/kg, 15mg/kg, 10mg/kg) was intraperitoneally administered for
      three consecutive days. MAO-B inhibitor pargyline (15mg/kg) was systemically
      administered before neurotoxin administration. The first MPTP dose induced an
      increase in dialysate dopamine and a decrease of DOPAC levels in striatal
      dialysate. After the first neurotoxin administration, increases in striatal
      glucose, lactate, pyruvate, lactate/pyruvate (L/P) and lactate/glucose (L/G)
      ratios were observed. Subsequent MPTP administrations showed a progressive
      reduction of dopamine, glucose and pyruvate levels with a concomitant further
      increase in lactate levels and L/P and L/G ratios. At day 1, pargyline pre
      treatment attenuated the MPTP-induced changes in all studied analytes. Starting
      from day 2, pargyline prevented the depletion of dopamine, glucose and pyruvate
      while reduced the increase of lactate, L/P ratio and L/G ratio. These in vivo
      results suggest a pargyline neuroprotection role against the MPTP-induced
      energetic impairment consequent to mitochondrial damage. This neuroprotective
      effect was confirmed by TH immunostaining of the substantia nigra. 

PMID- 24080404
TI  - Acral coldness in migraineurs.
AB  - In search for new biomarkers of vascular disturbances accompanying migraine, we
      compared the facial and hand skin temperatures in 41 women, including 12 migraine
      patients during the headache-free period and 29 healthy controls. Compared to the
      controls, the acral skin temperatures were lower in migraineurs, especially in
      those with right-sided headache. Our findings suggest that migraine is associated
      with a peripheral coldness possibly due to abnormal autonomic vascular control.
      The cold nose and hands may represent easily assessable biomarkers of these
      disorders. 

PMID- 24080405
TI  - The plant mitochondrial protein import apparatus - the differences make it
      interesting.
AB  - BACKGROUND: Mitochondria play essential roles in the life and death of almost all
      eukaryotic cells, ranging from single-celled to multi-cellular organisms that
      display tissue and developmental differentiation. As mitochondria only arose once
      in evolution, much can be learned from studying single celled model systems such
      as yeast and applying this knowledge to other organisms. However, two billion
      years of evolution have also resulted in substantial divergence in mitochondrial
      function between eukaryotic organisms. SCOPE OF REVIEW: Here we review our
      current understanding of the mechanisms of mitochondrial protein import between
      plants and yeast (Saccharomyces cerevisiae) and identify a high level of
      conservation for the essential subunits of plant mitochondrial import apparatus.
      Furthermore, we investigate examples whereby divergence and acquisition of
      functions have arisen and highlight the emerging examples of interactions between
      the import apparatus and components of the respiratory chain. MAJOR CONCLUSIONS:
      After more than three decades of research into the components and mechanisms of
      mitochondrial protein import of plants and yeast, the differences between these
      systems are examined. Specifically, expansions of the small gene families that
      encode the mitochondrial protein import apparatus in plants are detailed, and
      their essential role in seed viability is revealed. GENERAL SIGNIFICANCE: These
      findings point to the essential role of the inner mitochondrial protein
      translocases in Arabidopsis, establishing their necessity for seed viability and
      the crucial role of mitochondrial biogenesis during germination. This article is
      part of a Special Issue entitled Frontiers of Mitochondrial Research.

PMID- 24080406
TI  - Nonsteroidal anti-inflammatory drug sulindac sulfide suppresses structural
      protein Nesprin-2 expression in colorectal cancer cells.
AB  - BACKGROUND: Nonsteroidal anti-inflammatory drugs (NSAIDs) are well known for
      treating inflammatory disease and have been reported to have anti-tumorigenic
      effects. Their mechanisms are not fully understood, but both cyclooxygenase (COX)
      dependent and independent pathways are involved. Our goal was to shed further
      light on COX-independent activity. METHODS: Human colorectal cancer cells were
      observed under differential interference contrast microscopy (DICM), fluorescent
      microscopy, and micro-impedance measurement. Microarray analysis was performed
      using HCT-116 cells treated with sulindac sulfide (SS). PCR and Western blots
      were performed to confirm the microarray data and immunohistochemistry was
      performed to screen for Nesprin-2 expression. Micro-impedance was repeating
      including Nesprin-2 knock-down by siRNA. RESULTS: HCT-116 cells treated with SS
      showed dramatic morphological changes under DICM and fluorescent microscopy, as
      well as weakened cellular adhesion as measured by micro-impedance. Nesprin-2 was
      selected from two independent microarrays, based on its novelty in relation to
      cancer and its role in cell organization. SS diminished Nesprin-2 mRNA expression
      as assessed by reverse transcriptase and real time PCR. Various other NSAIDs were
      also tested and demonstrated that inhibition of Nesprin-2 mRNA was not unique to
      SS. Additionally, immunohistochemistry showed higher levels of Nesprin-2 in many
      tumors in comparison with normal tissues. Further micro-impedance experiments on
      cells with reduced Nesprin-2 expression showed a proportional loss of cellular
      adhesion. CONCLUSIONS: Nesprin-2 is down-regulated by NSAIDs and highly expressed
      in many cancers. GENERAL SIGNIFICANCE: Our data suggest that Nesprin-2 may be a
      potential novel oncogene in human cancer cells and NSAIDs could decrease its
      expression.

PMID- 24080408
TI  - Proteomic responses to metal-induced oxidative stress in hydrothermal vent-living
      mussels, Bathymodiolus sp., on the Southwest Indian Ridge.
AB  - Bathymodiolin mussels are amongst the dominant fauna occupying hydrothermal vent
      ecosystems throughout the World's oceans. This subfamily inhabits a highly
      ephemeral and variable environment, where exceptionally high concentrations of
      reduced sulphur species and heavy metals necessitate adaptation of specialised
      detoxification mechanisms. Whilst cellular responses to common anthropogenic
      pollutants are well-studied in shallow-water species, they remain limited in deep
      sea vent fauna. Bathymodiolus sp. were sampled from two newly-discovered vent
      sites on the Southwest Indian Ridge (Tiamat and Knuckers Gaff) by the remotely
      operated vehicle (ROV) Kiel 6000 during the RRS James Cook cruise, JC 067 in
      November 2011. Here, we use redox proteomics to investigate the effects of tissue
      metal accumulation on protein expression and thiol oxidation in gill. Following
      2D PAGE, we demonstrate a significant difference in intensity in 30 protein spots
      in this organ between the two vent sites out of 205 matched spots. We also see
      significant variations in thiol oxidation in 15 spots, out of 143 matched. At
      Tiamat, 23 protein spots are up-regulated compared to Knuckers Gaff and we
      identify 5 of these with important roles in metabolism, cell structure, stress
      response, and redox homeostasis. We suggest that increased metal exposure
      triggers changes in the proteome, regulating tissue uptake. This is evident both
      between vent sites and across a chemical gradient within the Knuckers Gaff vent
      site. Our findings highlight the importance of proteomic plasticity in successful
      adaptation to the spatially and temporally fluctuating chemical environments that
      are characteristic of hydrothermal vent habitats. 

PMID- 24080407
TI  - Alu elements: an intrinsic source of human genome instability.
AB  - Alu elements are ~300bp sequences that have amplified via an RNA intermediate
      leading to the accumulation of over 1 million copies in the human genome.
      Although a few of the copies are active, Alu germline activity is the highest of
      all human retrotransposons and does significantly contribute to genetic disease
      and population diversity. There are two basic mechanisms by which Alu elements
      contribute to disease: through insertional mutagenesis and as a large source of
      repetitive sequences that contribute to nonallelic homologous recombination
      (NAHR) that cause genetic deletions and duplications. 

PMID- 24080409
TI  - Molecular iodine (I2) emission from two Laminaria species (Phaeophyceae) and
      impact of irradiance and temperature on I2 emission into air and iodide release
      into seawater from Laminaria digitata.
AB  - Kelps of the genus Laminaria accumulate iodine at high concentrations, but the
      iodine retaining capacity can be affected by emersion and physiological stress.
      In this study, I2 emission into the atmosphere from Laminaria digitata and
      Laminaria hyperborea was compared under controlled low irradiances and
      temperatures. The two species exhibited different I2 emission rates as blades of
      L. digitata emitted I2 at rates five times higher than those from newly-grown
      blades (current growth season) of L. hyperborea. I2 emission was not detectable
      from old blades (previous growth season) of L. hyperborea. Additionally, effects
      of irradiance and temperature on both I2 emission into air and net I(-) release
      into seawater where assessed for L. digitata while monitoring photo-physiological
      parameters as stress indicators. Irradiances between 30 and 120 MUmol photons m(
      2) s(-1) had only marginal effects on both I2 emission and I(-) release rates,
      but physiological stress, indicated by photoinhibition, was observed. The results
      suggest that the irradiances applied here were not stressful enough to impact on
      the iodine release. By contrast, at elevated temperatures (20  degrees C),
      photoinhibition was accompanied by an increase in I2 emission rates, but net I(-)
      release rates remained similar at 10-20  degrees C. High I2 emission rates into
      air and I(-) release into seawater observed from L. digitata underpin the
      fundamental function of this kelp as mediator of coastal iodine fluxes.

PMID- 24080410
TI  - Vitellogenin as biomarker for estrogenicity in flounder Platichthys flesus in the
      field and exposed to 17alpha-ethinylestradiol via food and water in the
      laboratory.
AB  - The ability of 17alpha-ethinylestradiol (EE2) to elevate vitellogenin levels were
      investigated in male flounder Platichthys flesus and vitellogenin concentrations
      in flounders from the Danish coastal environment were determined. Male flounders
      were exposed to 17alpha-ethinylestradiol (EE2) via food or water. Average
      vitellogenin concentrations in the control fish ranged between 25 and 100 ng mL(
      )(1). Exposure to 5.1, 8.1 and 16.8 ng EE2 L(-)(1) in water and 500 and 5000 ng
      EE2 kg(-)(1) body weight (bw) every second day in the food increased the plasma
      vitellogenin concentration in a concentration and time dependent manner, whereas
      exposure to 2.7 ng EE2 L(-)(1) in water for 21 d and 5 and 50 ng EE2 kg(-)(1) bw
      for 12 days in the food did not. EE2 could be detected in liver and testes (but
      not in muscle) after exposure to 8.1 and 16.8 ng EE2 L(-)(1) in the water and
      5000 ng EE2 kg(-)(1) bw in the food; the highest concentration was 6 ng g(-)(1)
      wet weight in liver. The majority of the male flounders collected from nine
      coastal Danish sites from 1999 to 2004 had vitellogenin concentrations below 100
      ng mL(-)(1), and only at two sites moderate estrogenic inputs were indicated.

PMID- 24080411
TI  - The impact of rising sea temperature on innate immune parameters in the tropical
      subtidal sea urchin Lytechinus variegatus and the intertidal sea urchin
      Echinometra lucunter.
AB  - Ocean temperatures are rising throughout the world, making it necessary to
      evaluate the impact of these temperature changes on sea urchins, which are well
      known bioindicators. This study evaluated the effect of an increase in
      temperature on the immune response of the subtidal Lytechinus variegatus and the
      intertidal Echinometra lucunter sea urchins. Both species were exposed to 20
      (control), 25 and 30  degrees C temperatures for 24 h, 2, 7 and 14 days. Counting
      of coelomocytes and assays on the phagocytic response, adhesion and spreading of
      coelomocytes were performed. Red and colorless sphere cells were considered
      biomarkers for heat stress. Moreover, a significant decrease in the phagocytic
      indices and a decrease in both cell adhesion and cell spreading were observed at
      25 and 30  degrees C for L. variegatus. For E. lucunter, the only alteration
      observed was for the cell proportions. This report shows how different species of
      sea urchins respond immunologically to rising temperatures.

PMID- 24080412
TI  - Abnormalities in eelpout Zoarces viviparus upon chemical exposure.
AB  - Elevated frequencies of abnormal embryos in female eelpout Zoarces viviparus have
      been demonstrated in Danish, Swedish and German monitoring programmes at certain
      geographic locations with high levels of anthropogenic input. Pollutants present
      in areas with high malformation frequencies were selected and tested in a
      controlled laboratory experiment for their potential to induce abnormalities
      among eelpout embryos upon injection into pregnant eelpout. Tributyltin, 2,3,7,8
      tetrachlorodibenzo-p-dioxin, pyrene, nonylphenol, 2,2',4,4'-tetrabromophenylether
      and heptadecafluorooctanesulfonic acid were tested, either individually or
      combined. Generally, the chemicals were transferred to eggs and/or embryos. Some
      of the exposures increased the proportion of broods with more than 10% abnormal
      or 5% malformed embryos, although the average percentages of abnormal development
      were not affected. Spinal, cranial and eye deformities were evident, similarly to
      what is seen in nature. Some of the exposures resulted in increased percentages
      of females with as well a low reproductive capacity as embryos with a low
      condition index. 

PMID- 24080413
TI  - A method for environmental acoustic analysis improvement based on individual
      evaluation of common sources in urban areas.
AB  - Noise levels of common sources such as vehicles, whistles, sirens, car horns and
      crowd sounds are mixed in urban soundscapes. Nowadays, environmental acoustic
      analysis is performed based on mixture signals recorded by monitoring systems.
      These mixed signals make it difficult for individual analysis which is useful in
      taking actions to reduce and control environmental noise. This paper aims at
      separating, individually, the noise source from recorded mixtures in order to
      evaluate the noise level of each estimated source. A method based on blind
      deconvolution and blind source separation in the wavelet domain is proposed. This
      approach provides a basis to improve results obtained in monitoring and analysis
      of common noise sources in urban areas. The method validation is through
      experiments based on knowledge of the predominant noise sources in urban
      soundscapes. Actual recordings of common noise sources are used to acquire
      mixture signals using a microphone array in semi-controlled environments. The
      developed method has demonstrated great performance improvements in
      identification, analysis and evaluation of common urban sources. 

PMID- 24080415
TI  - A global assessment of climate-water quality relationships in large rivers: an
      elasticity perspective.
AB  - To uncover climate-water quality relationships in large rivers on a global scale,
      the present study investigates the climate elasticity of river water quality
      (CEWQ) using long-term monthly records observed at 14 large rivers. Temperature
      and precipitation elasticities of 12 water quality parameters, highlighted by N-
      and P-nutrients, are assessed. General observations on elasticity values show the
      usefulness of this approach to describe the magnitude of stream water quality
      responses to climate change, which improves that of simple statistical
      correlation. Sensitivity type, intensity and variability rank of CEWQ are
      reported and specific characteristics and mechanism of elasticity of nutrient
      parameters are also revealed. Among them, the performance of ammonia, total
      phosphorus-air temperature models, and nitrite, orthophosphorus-precipitation
      models are the best. Spatial and temporal assessment shows that precipitation
      elasticity is more variable in space than temperature elasticity and that
      seasonal variation is more evident for precipitation elasticity than for
      temperature elasticity. Moreover, both anthropogenic activities and environmental
      factors are found to impact CEWQ for select variables. The major relationships
      that can be inferred include: (1) human population has a strong linear
      correlation with temperature elasticity of turbidity and total phosphorus; and
      (2) latitude has a strong linear correlation with precipitation elasticity of
      turbidity and N nutrients. As this work improves our understanding of the
      relation between climate factors and surface water quality, it is potentially
      helpful for investigating the effect of climate change on water quality in large
      rivers, such as on the long-term change of nutrient concentrations. 

PMID- 24080414
TI  - Dynamic modelling of the long term behaviour of cadmium, lead and mercury in
      Swiss forest soils using CHUM-AM.
AB  - The applicability of the dynamic soil model CHUM-AM was tested to simulate
      concentrations of Cd, Pb and Hg in five Swiss forest soils. Soil cores of up to
      50 cm depth were sampled and separated into two defined soil layers. Soil
      leachates were collected below the litter by zero-tension lysimeters and at 15
      and 50 cm soil depths by tension lysimeters over two years. The concentrations of
      Cd, Pb and Hg in the solid phase and soil solution were measured by ICP-MS (Cd,
      Pb) or CV-AFS (Hg). Measured metal concentrations were compared with modelled
      concentrations using CHUM-AM. Additionally we ran the model with three different
      deposition scenarios (current deposition; maximum acceptable deposition according
      to the Swiss ordinance on Air Pollution Control; critical loads according to
      CLRTAP) to predict metal concentrations in the soils for the next 1000 years.
      Assuming current loads concentrations of Cd and Pb showed varying trends
      (increasing/decreasing) between the soils. Soils rich in organic carbon or with a
      high pH value showed increasing trends in Cd and Pb concentrations whereas the
      concentrations in the other soils decreased. In contrast Hg concentrations are
      predicted to further increase in all soils. Critical limits for Pb and Hg will
      partly be exceeded by current loads or by the critical loads proposed by the
      CLRTAP but the critical limits for Cd will rarely be reached within the next 1000
      years. In contrast, maximal acceptable deposition will partly lead to
      concentrations above the critical limits for Pb in soils within the next 400
      years, whereas the acceptable deposition of Cd will not lead to concentrations
      above the proposed critical limits. In conclusion the CHUM-AM model is able to
      accurately simulate heavy metal (Cd, Pb and Hg) concentrations in Swiss forest
      soils of various soil properties.

PMID- 24080416
TI  - The influence of weather and climate on the reliability of magnetic properties of
      tree leaves as proxies for air pollution monitoring.
AB  - Monthly monitoring of magnetic properties of Platanus hispanica tree leaves was
      used to assess atmospheric pollution in Madrid (Spain) and its suburban town of
      Pozuelo de Alarcon. Magnetic susceptibility, isothermal remanent magnetisation
      and metal concentrations were analysed to study the sources of atmospheric
      pollutants and their spatial and temporal evolution. In addition to urban dust,
      our results indicated that lithogenic dust and incorporation of trace metals in
      the leaf tissue also control the magnetic susceptibility of tree leaves. Global
      comparisons with cities of different climatic regimes suggest that air humidity
      is the key factor controlling the relative influence of pollutants, lithogenic
      dust and biological effects on the magnetic properties of tree leaves.
      Interaction of the atmosphere and tree leaves depends not only on local
      meteorology but also on climate. Climate, especially air humidity, and
      meteorology need to be considered when interpreting the magnetic properties of
      tree leaves as an atmospheric pollution tool. 

PMID- 24080417
TI  - Personal exposure to ultrafine particles: the influence of time-activity
      patterns.
AB  - Exposure to ultrafine particles (UFPs) is deemed to be a major risk affecting
      human health. Therefore, airborne particle studies were performed in the recent
      years to evaluate the most critical micro-environments, as well as identifying
      the main UFP sources. Nonetheless, in order to properly evaluate the UFP
      exposure, personal monitoring is required as the only way to relate particle
      exposure levels to the activities performed and micro-environments visited. To
      this purpose, in the present work, the results of experimental analysis aimed at
      showing the effect of the time-activity patterns on UFP personal exposure are
      reported. In particular, 24 non-smoking couples (12 during winter and summer
      time, respectively), comprised of a man who worked full-time and a woman who was
      a homemaker, were analyzed using personal particle counter and GPS monitors. Each
      couple was investigated for a 48-h period, during which they also filled out a
      diary reporting the daily activities performed. Time activity patterns, particle
      number concentration exposure and the related dose received by the participants,
      in terms of particle alveolar-deposited surface area, were measured. The average
      exposure to particle number concentration was higher for women during both summer
      and winter (Summer: women 1.8 * 10(4) part. cm(-3); men 9.2 * 10(3) part. cm(-3);
      Winter: women 2.9 * 10(4) part. cm(-3); men 1.3 * 10(4) part. cm(-3)), which was
      likely due to the time spent undertaking cooking activities. Staying indoors
      after cooking also led to higher alveolar-deposited surface area dose for both
      women and men during the winter time (9.12 * 10(2) and 6.33 * 10(2) mm(2),
      respectively), when indoor ventilation was greatly reduced. The effect of cooking
      activities was also detected in terms of women's dose intensity (dose per unit
      time), being 8.6 and 6.6 in winter and summer, respectively. On the contrary, the
      highest dose intensity activity for men was time spent using transportation (2.8
      in both winter and summer).

PMID- 24080418
TI  - Natural and anthropogenic factors affecting the groundwater quality in Serbia.
AB  - Various chemometric techniques were used to analyze the quality of groundwater
      data sets. Seventeen water quality parameters: the cations Na, K, Ca, Mg, the
      anions Cl, SO4, NO3, HCO3 and nine trace elements Pb, As, Mn, Ni, Cu, Cd, Fe, Zn
      and Cr were measured at 66 different key sampling sites in ten representative
      areas (low land-Northern Autonomous Province of Serbia, Vojvodina and central
      Serbia) for the summer period of 2009. HCA grouped the sample sites into four
      clusters based on the similarities of the characteristics of the groundwater
      quality. DA showed two parameters, HCO3 and Zn, affording more than 90% correct
      assignments in the spatial analysis of four/three different regions in Serbia.
      Factor analysis was applied on the log-transformed data sets and allowed the
      identification of a reduced number of factors with hydrochemical meaning. The
      results showed severe pollution with Mn, As, NO3, Ni, Pb whereby anthropogenic
      origin of these contaminants was indicated. The pollution comes from both
      scattered point sources (industrial and urban effluent) and diffuse source
      agricultural activity. These samples may not be suitable for human consumption;
      the water quality belongs to class III/IV (contaminated). The Fe anomalies
      (7.1mg/L) in the water from the Vetrnica site can be attributed to natural
      sources, such as the dissolution of rock masses and rock fragments. The serious
      groundwater contamination with As (25.7-137.8 MUg/L) in the area of Banat
      (Northern Autonomous Province of Serbia, Vojvodina) and a sample No. 9 at the
      Great Morava River requires urgent attention.

PMID- 24080419
TI  - Effects of anthropogenic salinization on biological traits and community
      composition of stream macroinvertebrates.
AB  - Salinization of rivers resulting from industrial discharge or road-deicing can
      adversely affect macroinvertebrates. Trait-based approaches are a promising tool
      in ecological monitoring and may perform better than taxonomy-based approaches.
      However only little is known how and which biological traits are affected by
      salinization. We investigated the effects of anthropogenic salinization on
      macroinvertebrate communities and biological traits in the Werra River, Germany
      and compared the taxonomic and trait response. We found a change in
      macroinvertebrate community and trait composition. Communities at saline sites
      were characterized by the three exotic species Gammarus tigrinus, Apocorophium
      lacustre and Potamopyrgus antipodarum. The frequencies of trait modalities long
      life cycle duration, respiration by gill, ovoviviparity, shredder and
      multivoltinism were statistically significantly increased at saline sites. The
      trait-based ordination resulted in a higher explained variance than the taxonomy
      based ordination, indicating a better performance of the trait-based approach,
      resulting in a better discrimination between saline and non-saline sites. Our
      results are in general agreement with other studies from Europe, indicating a
      trait convergence for saline streams, being dominated by the traits ovoviviparity
      and multivoltinism. Three further traits (respiration by gill, life cycle
      duration and shredders) responded strongly to salinization, but this may
      primarily be attributed to the dominance of a single invasive species, G.
      tigrinus, at the saline sites in the Werra River. 

PMID- 24080420
TI  - DNA biosensor/biochip for multiplex blood group genotyping.
AB  - At present, 33 blood groups representing over 300 antigens are listed by the
      International Society of Blood Transfusion (ISBT). Most of them result from a
      single nucleotide polymorphism (SNP) in the corresponding DNA sequence, i.e.
      approx. 200 SNPs. In immunohematology laboratories, blood group determination is
      classically carried out by serological tests, but these have some limitations,
      mostly in term of multiplexing and throughput. Yet, there is a growing need of
      extended blood group typing to prevent alloimmunization in transfused patients
      and transfusion accidents. The knowledge of the molecular bases of blood groups
      allows the use of molecular biology methods within immunohematology laboratories.
      Numerous assays focused on blood group genotyping were developed and described
      during the last 10 years. Some of them were real biochips or biosensors while
      others were more characterized by the particular molecular biology techniques
      they used, but all were intending to produce multiplex analysis. PCR techniques
      are most of the time used followed by an analytical step involving a DNA
      biosensor, biochip or analysis system (capillary electrophoresis, mass
      spectrometry). According to the method used, the test can then be classified as
      low-, medium- or high-throughput. There are several companies which developed
      platforms dedicated to blood group genotyping able to analyze simultaneously
      various SNPs or variants associated with blood group systems. This review
      summarizes the characteristics of each molecular biology method and medium-/high
      throughput platforms dedicated to the blood group genotyping.

PMID- 24080421
TI  - Perioperative and clinical outcomes in the management of epithelial ovarian
      cancer using a robotic or abdominal approach.
AB  - OBJECTIVE: To evaluate the feasibility and efficacy of robotic-assisted
      management of epithelial ovarian cancer. METHODS: Retrospective review of robotic
      assisted or abdominal ovarian cancer cases presenting with pelvic mass, initial
      staging, or debulking after neoadjuvant chemotherapy performed by a single
      surgeon (2008-2012). Patient characteristics and outcomes were compared using chi
      squared or Student's t-tests. RESULTS: There were 63 robotic and 26 abdominal
      cases. Patient characteristics were similar for age, uterine weight, and BMI,
      with prior abdominal surgery more common in the abdominal group (p=0.0257).
      Robotic operative time was longer (p<0.0001), while blood loss (p<0.0001) and
      hospital stay (p=0.0009) were reduced. Major complication rates (16% vs. 23%,
      p=0.4209) and lymphadenectomy yields (13 vs. 11 nodes, p=0.2310) were similar.
      Neoadjuvant chemotherapy was more common in the robotic group (52% vs. 15%,
      p=0.0013). Residual disease rates for all cases (73% vs. 50%, p=0.880) and for
      Stage II-IV cases (61% vs. 40%, p=0.929) were equivalent. Follow-up was longer
      for the abdominal group; however, an equivalent percentage of patients had at
      least 1 year of follow-up (57% vs. 77%, p=0.0789). At 1 year, survival and no
      evidence of disease (NED) rates were equivalent for all cases (survival: 97% vs.
      90%, p=0.2501; NED: 81% vs. 85%, p=0.6773) and for Stage II-IV cases (survival:
      96% vs. 88%, p=0.3080; NED: 76% vs. 81%, p=0.6920). CONCLUSIONS: A robotic
      approach for the management of epithelial ovarian cancer, including patients
      treated with neoadjuvant chemotherapy, is feasible and effective. Debulking,
      recurrence, and survival rates were similar to laparotomy at 1 year.

PMID- 24080422
TI  - Low-molecular-mass secretome profiling identifies C-C motif chemokine 5 as a
      potential plasma biomarker and therapeutic target for nasopharyngeal carcinoma.
AB  - Cancer cell secretome profiling has been shown to be a promising strategy for
      identifying potential body fluid-accessible cancer biomarkers and therapeutic
      targets. However, very few reports have investigated low-molecular-mass (LMr)
      proteins (<15kDa) in the cancer cell secretome. In the present study, we applied
      tricine-SDS-gel-assisted fractionation in conjunction with LC-MS/MS to
      systemically identify LMr proteins in the secretomes of three nasopharyngeal
      carcinoma (NPC) cell lines. We examined two NPC tissue transcriptome datasets to
      identify LMr genes/proteins that are highly upregulated in NPC tissues and also
      secreted/released from NPC cells, obtaining 35 candidates. We verified the
      overexpression of four targets (LSM2, SUMO1, RPL22, and CCL5) in NPC tissues by
      immunohistochemistry and demonstrated elevated plasma levels of two targets
      (S100A2 and CCL5) in NPC patients by ELISA. Notably, plasma CCL5 showed good
      power (AUC 0.801) for discriminating NPC patients from healthy controls.
      Additionally, functional assays revealed that CCL5 promoted migration of NPC
      cells, an effect that was effectively blocked by CCL5-neutralizing antibodies and
      maraviroc, a CCL5 receptor antagonist. Collectively, our data indicate the
      feasibility of the tricine-SDS-gel/LC-MS/MS approach for efficient identification
      of LMr proteins from cancer cell secretomes, and suggest that CCL5 is a potential
      plasma biomarker and therapeutic target for NPC. BIOLOGICAL SIGNIFICANCE: Both
      LMr proteome and cancer cell secretome represent attractive reservoirs for
      discovery of cancer biomarkers and therapeutic targets. Our present study
      provides evidence for the practicality of using the tricine-SDS-PAGE/LC-MS/MS
      approach for in-depth identification of LMr proteins from the NPC cell
      secretomes, leading to the discovery of CCL5 as a potential plasma biomarker and
      therapeutic target for NPC. We believe that the modified GeLC-MS/MS approach used
      here can be further applied to explore extremely low-abundance, extracellular LMr
      proteins with important biological functions in other cell lines and
      biospecimens.

PMID- 24080423
TI  - Detection of Listeria monocytogenes from selective enrichment broth using MALDI
      TOF Mass Spectrometry.
AB  - Conventional methods used for primary detection of Listeria monocytogenes from
      foods and subsequent confirmation of presumptive positive samples involve
      prolonged incubation and biochemical testing which generally require four to five
      days to obtain a result. In the current study, a simple and rapid proteomics
      based MALDI-TOF MS approach was developed to detect L. monocytogenes directly
      from selective enrichment broths. Milk samples spiked with single species and
      multiple species cultures were incubated in a selective enrichment broth for 24h,
      followed by an additional 6h secondary enrichment. As few as 1 colony-forming
      unit (cfu) of L. monocytogenes per mL of initial selective broth culture could be
      detected within 30h. On applying the same approach to solid foods previously
      implicated in listeriosis, namely chicken pate, cantaloupe and Camembert cheese,
      detection was achieved within the same time interval at inoculation levels of
      10cfu/mL. Unlike the routine application of MALDI-TOF MS for identification of
      bacteria from solid media, this study proposes a cost-effective and time-saving
      detection scheme for direct identification of L. monocytogenes from broth
      cultures.This article is part of a Special Issue entitled: Trends in Microbial
      Proteomics. BIOLOGICAL SIGNIFICANCE: Globally, foodborne diseases are major
      causes of illness and fatalities in humans. Hence, there is a continual need for
      reliable and rapid means for pathogen detection from food samples. Recent
      applications of MALDI-TOF MS for diagnostic microbiology focused on detection of
      microbes from clinical specimens. However, the current study has emphasized its
      use as a tool for detecting the major foodborne pathogen, Listeria monocytogenes,
      directly from selective enrichment broths. This proof-of-concept study proposes a
      detection scheme that is more rapid and simple compared to conventional methods
      of Listeria detection. Very low levels of the pathogen could be identified from
      different food samples post-enrichment in selective enrichment broths. Use of
      this scheme will facilitate rapid and cost-effective testing for this important
      foodborne pathogen.

PMID- 24080424
TI  - Brain network interactions in health and disease.
AB  - Understanding how brain systems interact to produce complex behaviors is a
      central goal of cognitive neuroscience. Palaniyappan and colleagues enhance our
      understanding of how interactions among brain systems contribute to individual
      differences in function and psychopathology by examining causal interactions
      among the salience and central executive systems in schizophrenia. 

PMID- 24080425
TI  - Effect of preillumination with red light on photosynthetic parameters and oxidant
      /antioxidant balance in Arabidopsis thaliana in response to UV-A.
AB  - The effect of preillumination with low intensity (10MUmol quanta m(-2)s(-1),
      10min) light of different wavelengths in the spectral range of 550-730nm on
      photosynthesis and activity of PSII, the content of photosynthetic pigments and
      H2O2, as well as the peroxidase activity in the leaves of 26-d-old Arabidopsis
      thaliana wild-type (WT) plants in response to UV-A radiation was studied. UV-A
      decreased the activity of the PSII, the content of Chl a, Chl b and carotenoids,
      as well as increased the peroxidase activity and H2O2 level in the WT leaves.
      Preillumination of the leaves with red light (RL, lambdamax=664nm) reduced the
      inhibitory effect of UV radiation on photosynthesis and activity of the PSII,
      indicated by delayed light emission as well as the H2O2 level, but increased the
      peroxidase activity in the leaves compared to illumination by UV radiation only.
      Illumination with RL alone and the subsequent exposure of plants to darkness
      increased the peroxidase activity and the transcription activity of genes of the
      transcription factors APX1 and HYH. Preillumination of leaves with RL, then far
      red light (FRL, lambdamax=727nm) partially compensated the effect of the RL for
      all studied parameters, suggesting that the active form of phytochrome (PFR) is
      involved in these processes. Preillumination with the wavelengths of 550, 594 and
      727nm only did not have a marked effect on photosynthesis. The hy2 mutant of
      Arabidopsis with reduced synthesis of the phytochrome B chromophore showed
      decreased resistance of PSII to UV-A compared with the WT of Arabidopsis. UV
      radiation reduced Chl a fluorescence much faster in the hy2 mutant compared to
      the WT. Preillumination of the hy2 mutant with RL did not affect the PSII
      activity and H2O2 level in UV-irradiated leaves. It is assumed that the formation
      of the increased resistance of the photosynthetic apparatus of Arabidopsis to UV
      A radiation involves PFR and the antioxidant system of plants, partly by inducing
      transcriptional activity of some antioxidant and transcription factors genes. 

PMID- 24080426
TI  - Re. 'doppler ultrasound examination of multiple sclerosis patients and control
      participants: inter-observer agreement and association with disease'.

PMID- 24080427
TI  - Translational research: the interplay between research and nursing practice.

PMID- 24080428
TI  - Transcriptional changes in rat alpha-motoneurons resulting from increased
      physical activity.
AB  - Electrophysiological properties of lumbar alpha-motoneurons change after chronic
      increases and decreases in hindlimb neuromuscular activity. Although modeling of
      these changes suggests that motoneurons probably alter gene expression in these
      situations, there is no evidence that this is the case. In this study, we
      measured the content of several mRNAs in lumbar motoneurons, harvested using
      laser capture microdissection, from rats previously subjected to normal cage
      activity, voluntary wheel exercise for 16weeks, and forced treadmill training for
      7days and 16weeks. As a result of the prolonged daily treadmill training, but not
      the voluntary wheel training, significant increases occurred in muscle peroxisome
      proliferator-activated receptor gamma, coactivator 1 alpha (PGC-1alpha) mRNA, and
      in muscle PGC-1alpha and cytochrome oxidase proteins, in soleus and plantaris
      muscles. Significant changes in mRNA contents (decreases) were evident for the
      receptors 5-hydroxytryptamine (serotonin) receptor 1A (5HT1a), GABA A receptor,
      subunit alpha 2 (GABAAalpha2), and for the potassium conductance calcium
      activated channel protein (SK2) in the motoneurons from 16-week-trained rats, and
      for glutamate receptor, metabotropic 1 (mGluR1) in the voluntary wheel-trained
      rats. Motoneurons from 16-week treadmill-trained rats also did not demonstrate
      the decreases in several mRNAs that were evident after 7days of treadmill
      exercise, suggesting an adaptation of motoneurons to acute stress. The mRNA
      changes following prolonged daily treadmill training are consistent with a
      reduction in inhibitory influences onto motoneurons, and a transition toward
      motoneurons that innervate slower contracting muscle fibers. These results
      demonstrate that the previously reported physiological changes in motoneurons
      with altered activity are accompanied by changes in gene expression. 

PMID- 24080429
TI  - Contribution of the lateral lemniscus to the control of swallowing in decerebrate
      cats.
AB  - Lateral lemniscus, a relay nucleus of auditory sensation, is involved in the
      control of phonatory movements such as human speech and vocalization of animals.
      The present study was designed to test whether neurons in the lateral lemniscus
      contributed to the control of swallowing, one of non-phonic oro-pharyngolaryngeal
      movements. In acutely decerebrated cats (n=15), swallowing was induced by
      electrical stimulation (20-80MUA at 10Hz for 20s with rectangular pulses of 0.2ms
      duration) delivered to the superior laryngeal nerve (SLN). Repetitive electrical
      stimulation (30-50MUA at 50Hz for 10-20s) applied to the dorsal nucleus of the
      lateral lemniscus (LLD) increased the number and reduced the latency to the onset
      of the SLN-induced swallowing. On the other hand, stimulation of the ventral
      nucleus of the lateral lemniscus and the paralemniscal area, corresponding to the
      ventrolateral part of the parabrachial nucleus and the Kolliker-Fuse nucleus,
      often suppressed the SLN-induced swallowing. Microinjection of NMDA (0.1-0.15MUl,
      5.0-10mM) into the LLD through a stereotaxically placed glass micropipette
      facilitated the SLN-induced swallowing, i.e., the number was increased and the
      latency of swallowing was reduced. We also injected muscimol (a gamma amino
      butyric acid (GABA)A receptor agonist), bicuculline (a GABAA receptor antagonist)
      and baclofen (a GABAB receptor agonist) into the LLD (0.1-0.15MUl and 5.0mM for
      each substance). It was observed that an injection of muscimol suppressed the SLN
      induced swallowing. However, an injection of bicuculline facilitated the
      swallowing. An injection of baclofen did not alter the swallowing. These results
      suggest the presence of functional topography in the lateral lemniscus and the
      paralemniscal area in relation to the control of swallowing. The facilitatory LLD
      effects on swallowing are modulated by glutamatergic and GABAergic receptors on
      neurons in the LLD. 

PMID- 24080430
TI  - Utilization management in the clinical laboratory: an introduction and overview
      of the literature.
AB  - There is a broad literature addressing the need for improving utilization
      management in medical care. Numerous review articles and case studies have
      described approaches to utilization management challenges in the laboratory. This
      article will present an overview of the literature on laboratory utilization
      management and will compile a "toolbox" of strategies that can be used to address
      specific utilization management initiatives. A clear theme among successful
      utilization management programs is the need to recruit institutional champions
      both for the overall utilization management program and for ad hoc assistance
      with specific utilization challenges. It is important that these individuals
      represent a cross section of laboratory and clinical specialties and that the
      group be organized as a committee that has been established by the administrative
      and physician leadership of the organization. The changing nature of healthcare
      reimbursement will likely provide increased motivation to control laboratory
      testing and costs. Clinical pathologists are in a unique position to observe
      testing behavior patterns, suggest alternatives, implement order entry changes,
      manage testing algorithms and provide interpretive services for laboratory
      testing. For these reasons, clinical pathologists have a major opportunity to
      become institutional leaders in utilization management. 

PMID- 24080432
TI  - Utilization management in the core laboratory.
AB  - The need for appropriate utilization management of diagnostic testing is
      increasingly important. The majority of laboratory tests are performed in highly
      automated core laboratories that combine chemistry, immunoassays, hematology,
      coagulation and esoteric assays. These core laboratories are designed for high
      throughput leveraging economies of scale to produce large numbers of test results
      relatively inexpensively. Most core laboratory tests can be categorized based on
      whether they should or should not be ordered at all and, if so, by the frequency
      with which test ordering is reasonably appropriate (e.g. unrestricted, daily,
      weekly, monthly, yearly or once in a lifetime). Classifying tests by this
      approach facilitates electronic rule-based logic to detect which tests are
      appropriate for a given clinical indication. 

PMID- 24080431
TI  - Utilization management in the blood transfusion service.
AB  - The scope of activity of the Blood Transfusion Service (BTS) makes it unique
      among the clinical laboratories. The combination of therapeutic and diagnostic
      roles necessitates a multi-faceted approach to utilization management in the BTS.
      We present our experience in utilization management in large academic medical
      center. 

PMID- 24080433
TI  - An alternative perspective on how laboratory medicine can contribute to solve the
      health care crisis: a model to save costs by acquiring excellence in diagnostic
      systems.
AB  - The rapid escalation in health care costs has led to the idea to deliver better
      care at lower costs, reshaping the responsibilities of the health care system to
      achieve the goal of creating value for the patient. The pressure for fiscal
      containment and the progressive reduction in available health care resources
      originated very short term strategies consisting of abrupt reductions in
      expenditure, specifically in the provision of clinical pathology laboratory
      medicine services. However, the impact of laboratory test results on diagnostic
      and therapeutic interventions has increased enormously in the past decade, due to
      advances in personalized medicine and to the strictly correlated requirement to
      use new biomarkers with increasing sensitivity and specificity in clinical
      practice. In order to create savings by delivering better care there is the need
      to invest financial resources in purchasing high technology and new sophisticated
      tests and to promote the expertise of clinical pathologists and laboratory
      medicine professionals. This approach to creating value in patient health care is
      more productive and sustainable ethically, morally and economically as a long
      term strategy. It can be successfully achieved by applying defined rules that
      make public-private cooperation clearer, skipping incompatible solutions such as
      transforming clinical laboratories to 'industrially productive premises',
      outsourcing laboratory medicine services and using central acquisition of
      diagnostic systems. 

PMID- 24080434
TI  - Utilization management in microbiology.
AB  - The available literature concerning utilization management in the clinical
      microbiology laboratory is relatively limited compared with that for high-volume,
      automated testing in the central Core Laboratory. However, the same strategies
      employed elsewhere in the clinical laboratory operation can be applied to
      utilization management challenges in microbiology, including decision support
      systems, application of evidence-based medicine, screening algorithms and
      gatekeeper functions. The results of testing in the microbiology laboratory have
      significant effects on the cost of clinical care, especially costs related to
      antimicrobial agents and infection control practices. Consequently many of the
      successful utilization management interventions described in clinical
      microbiology have targeted not just the volume of tests performed in the
      laboratory, but also the downstream costs of care. This article will review
      utilization management strategies in clinical microbiology, including specific
      examples from our institution and other healthcare organizations. 

PMID- 24080435
TI  - Delta neutrophil index discriminates true bacteremia from blood culture
      contamination.
AB  - BACKGROUND: Delta neutrophil index (DNI) has been reported to be useful in the
      diagnosis of sepsis. We evaluated the role of DNI for differentiating true
      bacteremia from blood contamination and compared the DNI value with previously
      validated markers such as procalcitonin (PCT) and C-reactive protein (CRP).
      METHODS: The blood culture positive group was subdivided into true bacteremia
      (n=199) and contamination (n=158). The blood cultures were incubated in the
      BacT/Alert 3D (bioMerieux, Marcyl'Etoile, France) and BACTEC FX (Becton
      Dickinson, Sparks, MD, USA) systems for 5days. Data of complete blood cell count
      were collected from an automatic cell analyzer (ADVIA2120 Hematology System,
      Siemens Healthcare Diagnostics) to calculate DNI. RESULTS: Concentrations for
      DNI, PCT, and CRP were significantly higher in the true bacteremia group. When
      the gram-positive and gram-negative infections were compared among true
      bacteremia, only PCT was increased significantly in GNB bacteremia. DNI levels
      were well correlated with PCT (r=0.564, P<0.0001) and CRP (r=0.344, P<0.001)
      using the Spearman test among the culture positive bacteremia. The area under the
      ROC curve was 0.75 for PCT, 0.69 for CRP, and 0.69 for DNI. CONCLUSIONS: We
      demonstrated the usefulness of DNI in differentiating true bacteremia from
      contamination in patients with a positive blood culture.

PMID- 24080436
TI  - Effects of a fish-based diet and administration of pure eicosapentaenoic acid on
      brachial-ankle pulse wave velocity in patients with cardiovascular risk factors.
AB  - BACKGROUND AND PURPOSE: Brachial-ankle pulse wave velocity (baPWV) and ratio of
      plasma eicosapentaenoic acid to arachidonic acid (EPA/AA ratio) are surrogate
      markers for coronary artery disease (CAD). We aimed to evaluate the effects of a
      fish-based diet and administration of EPA on baPWV and plasma EPA/AA ratio.
      METHODS AND RESULTS: The changes in baPWV and plasma EPA/AA ratio were compared
      before and after a 6-month fish-based diet in 191 patients with cardiovascular
      risk factors. A fish-based diet resulted in significant increment of plasma
      EPA/AA ratio (0.40+/-0.18 vs. 0.49+/-0.27, p<0.001), with baPWV remaining
      unchanged. Multivariate analysis revealed that systolic blood pressure (SBP) (6
      month SBP-baseline SBP) and CAD were positively associated with increased baPWV
      (CAD: odds ratio=2.040, p=0.0436, SPB: odds ratio=1.056, p=0.0003). When the
      patients were divided into three groups: CAD, low-risk, and high-risk with no
      prior history of CAD according to the number of risk factors at baseline,
      comparison among the three groups disclosed an inter-group difference in the
      magnitude of change in baPWV (low-risk: -35+/-164cm/s, high-risk: -14+/-190cm/s,
      CAD: 39+/-164cm/s, p=0.0071 for trend). In 191 patients who had received a 6
      month fish-based diet, 21 patients (primarily CAD patients) sequentially received
      high purity EPA (1800mg/day) for 6 months. It resulted in marked increment of
      plasma EPA/AA ratio (0.65+/-0.57 vs. 1.19+/-0.46, p<0.001), accompanied by
      significant reduction in baPWV (1968+/-344cm/s vs. 1829+/-344cm/s, p=0.0061).
      There was a significant negative correlation between changes in baPWV and changes
      in plasma EPA/AA ratio in patients with a fish-based diet and sequential
      administration of EPA (r=-0.446, p=0.017). CONCLUSION: A fish-based diet was
      effective against increased baPWV only in low-risk patients, with slight
      increment of plasma EPA/AA. In high-risk patients and CAD patients,
      administration of EPA for preventing progression of baPWV endorsed the validity
      of high purity EPA administration recommended in the current guidelines.

PMID- 24080437
TI  - Nodular fasciitis of the hand: excision preserving 'vital' structures.
AB  - Nodular fasciitis is an extremely rare benign fibrous tumour of the hand.
      Although benign, the tumour is frequently adherent to tendons/nerves and joints
      of the hand. However, the tumour may spontaneously regress and does not tend to
      recur following excision with histologically positive margins. For the last 20
      years, the author has adopted a specific management approach for these and other
      benign fibrous tumours of the hand. Following the clinical/radiological
      diagnosis, tumour excision is done preserving 'vital' structures within the hand.
      The diagnosis is confirmed histologically and by immune stains, and the patient
      is then followed up for local recurrence. Over a 20-year period, the author has
      treated four cases of nodular fasciitis of the hand using this management
      approach. Despite the positive margins in all cases, there were no recurrences at
      a minimum follow-up interval of 3 years. 

PMID- 24080438
TI  - Hereditary neuropathy with liability to pressure palsy: global neuropathy after
      tourniquet use.

PMID- 24080439
TI  - Anodal transcranial direct current stimulation (tDCS) over the motor cortex
      increases sympathetic nerve activity.
AB  - BACKGROUND: Transcranial direct current stimulation (tDCS) is currently being
      investigated as a non-invasive neuromodulation therapy for a range of conditions
      including stroke rehabilitation. tDCS affects not only the area underlying the
      electrodes but also other areas of the cortex and subcortical structures. This
      could lead to unintended alteration in brain functions such as autonomic control.
      OBJECTIVE: We investigated the potential effects of tDCS on cardiovascular
      autonomic function in healthy volunteers. METHODS: Anodal (n = 14) or cathodal (n
      = 8) tDCS at 1 mA was applied over the primary motor cortex with the second
      electrode placed on the contralateral supraorbital region. Subjects visited the
      department twice and received active or sham tDCS for 15 min. Heart rate, blood
      pressure and respiration were recorded at baseline, during tDCS and after
      stimulation. Heart rate variability (HRV) was calculated using spectral analysis
      of beat-to-beat intervals derived from ECG data. Microneurography was also used
      to record muscle sympathetic nerve activity (MSNA; n = 5). RESULTS: Anodal tDCS
      caused a significant shift in HRV toward sympathetic predominance (P = 0.017),
      whereas there was no significant change in the cathodal or sham groups.
      Microneurography results also showed a significant increase in MSNA during anodal
      tDCS that continued post-stimulation. CONCLUSIONS: Anodal tDCS of the motor
      cortex shifts autonomic nervous system balance toward sympathetic dominance due
      at least in part to an increase in sympathetic output. These results suggest
      further investigation is warranted on tDCS use in patient groups with potential
      autonomic dysfunction, such as stroke patients.

PMID- 24080440
TI  - Introduction at the special issue on implications of cancer stem/progenitor cell
      concepts in molecular oncology and novel targeted therapies.

PMID- 24080441
TI  - Maximization of volatile fatty acids production from alginate in acidogenesis.
AB  - In this study, the response surface methodology (RSM) was applied to determine
      the optimum fermentative condition of alginate with the respect to the
      simultaneous effects of alginate concentration and initial pH to maximize the
      production of total volatile fatty acids (TVFAs) and alcohols. The results showed
      that the alginate fermentation was significantly affected by initial pH than by
      alginate concentration and there was no interaction between the two variables.
      The optimum condition was 6.2g alginate/L and initial pH 7.6 with a maximum TVFAs
      yield of 37.1%. Acetic acids were the main constituents of the TVFAs mixtures
      (i.e., 71.9-95.5%), while alcohols (i.e., ethanol, butanol, and propanol) were
      not detected. 

PMID- 24080442
TI  - Biodegradation of 1,2,3,4-tetrachlorodibenzo-p-dioxin in liquid broth by brown
      rot fungi.
AB  - Dioxins are a class of extremely hazardous molecules that might pose a threat to
      the environment. This work evaluated the microbial degradation of 1,2,3,4
      tetrachlorodibenzo-p-dioxin (1,2,3,4-TCDD), in liquid broth using three brown-rot
      fungi and one white-rot fungi as control. A fast and reliable extraction method
      with recoveries of over 98% together with a validated GC-MS method was developed,
      and applied to quantify 1,2,3,4-TCDD in liquid broth, mycelia and reaction flask,
      with detection limits of 10 ppb. Among the four strains tested, brown-rot fungus
      Aspergillus aculeatus showed best results, removing up to 21% of dioxin after 30
      day incubation. The results open both a path for biotechnological interest in
      bioremediation purposes and environmental behavior studies by using brown-rot
      fungus.

PMID- 24080443
TI  - Increased thermal stability of cold-adapted esterase at ambient temperatures by
      immobilization on graphene oxide.
AB  - In this study, the effect of graphene oxide (GO) on the thermal stability of a
      recombinant esterase from cold-adapted Pseudomonas mandelii, rEstKp, was
      investigated. The complex GO-rEstKp was formed by cross-linking. Both free rEstKp
      and GO-rEstKp complex showed similar optimum pH and temperatures. GO-rEstKp
      complex exhibited enhanced thermal stability at ambient temperatures than rEstKp,
      which prevented the denaturation of the enzyme by hydrophilic interactions.
      However, the catalytic efficiency of GO-rEstKp complex was lowered to
      approximately 40% of that of free rEstKp. This study provides an insight into the
      addition of GO for industrial applications of cold-adapted enzymes at ambient
      temperatures.

PMID- 24080444
TI  - Low solvent, low temperature method for extracting biodiesel lipids from
      concentrated microalgal biomass.
AB  - An industrially relevant method for disrupting microalgal cells and
      preferentially extracting neutral lipids for large-scale biodiesel production was
      demonstrated on pastes (20-25% solids) of Nannochloropsis sp. The highly
      resistant Nannochloropsis sp. cells. were disrupted by incubation for 15 h at 37
      degrees C followed by high pressure homogenization at 1200 +/- 100 bar. Lipid
      extraction was performed by twice contacting concentrated algal paste with
      minimal hexane (solvent:biomass ratios (w/w) of <2:1 and <1.3:1) in a stirred
      vessel at 35 degrees C. Cell disruption prior to extraction increased lipid
      recovery 100-fold, with yields of 30-50% w/w obtained in the first hexane
      contact, and a further 6.5-20% in the second contact. The hexane preferentially
      extracted neutral lipids over glyco- and phospholipids, with up to 86% w/w of the
      neutral lipids recovered. The process was effective on wet concentrated paste,
      required minimal solvent and moderate temperature, and did not require difficult
      to recover polar solvents.

PMID- 24080445
TI  - IGF2 and cancer.
AB  - Insulin-like growth factor 2 (IGF2) is a 7.5  kDa mitogenic peptide hormone
      expressed by liver and many other tissues. It is three times more abundant in
      serum than IGF1, but our understanding of its physiological and pathological
      roles has lagged behind that of IGF1. Expression of the IGF2 gene is strictly
      regulated. Over-expression occurs in many cancers and is associated with a poor
      prognosis. Elevated serum IGF2 is also associated with increased risk of
      developing various cancers including colorectal, breast, prostate and lung. There
      is established clinical utility for IGF2 measurement in the diagnosis of non
      islet cell tumour hypoglycaemia, a condition characterised by a molar IGF2:IGF1
      ratio >10. Recent advances in understanding of the pathophysiology of IGF2 in
      cancer have suggested much novel clinical utility for its measurement.
      Measurement of IGF2 in blood and genetic and epigenetic tests of the IGF2 gene
      may help assess cancer risk and prognosis. Further studies will determine whether
      these tests enter clinical practice. New therapeutic approaches are being
      developed to target IGF2 action. This review provides a clinical perspective on
      IGF2 and an update on recent research findings.

PMID- 24080447
TI  - The effect of extension constraint knee bracing on dynamic balance, gait
      mechanics, and joint alignment.
AB  - OBJECTIVE: To examine how an extension constraint knee brace affects active and
      passive standing knee joint alignment, dynamic balance, and gait mechanics.
      DESIGN: Repeated-measures, within-subjects design. SETTING: Research laboratory.
      PARTICIPANTS: Persons (N = 24) with no current diagnosed gait dysfunction or
      neuromuscular limitations that limit activities of daily living. METHODS: All
      subjects were tested with use of dynamic balance and gait analysis. Dynamic
      balance was examined with the Lower Quarter Y Balance Test. Gait analysis was
      conducted at a freely chosen walking speed for 2 conditions: (1) use of a brace
      with free range of motion (FROM) and (2) use of a brace with 30-degree extension
      constraint (ECON). In a subset of subjects, radiographs were used to examine
      standing knee alignment for 3 conditions: (1) FROM, (2) use of a knee ECON brace
      in a relaxed position; and (3) use of a knee ECON brace with maximal volitional
      quadriceps contraction. MAIN OUTCOME MEASURES: Peak knee flexion, knee flexion
      range of motion, peak vertical ground reaction force during weight acceptance and
      propulsion, and maximum reach distance in the anterior, posteromedial, and
      posterolateral directions were measured. RESULTS: Differences in dynamic balance
      were observed between ECON and FROM for the anterior reach. Peak knee flexion
      increased 3.2 degrees  and peak knee extension decreased 7.4 degrees  in the ECON
      condition. Vertical GRF values were found to increase bilaterally during ECON at
      midstance but decreased bilaterally during propulsion. Radiographic images
      revealed that the ECON elicited a 22.2 degrees  flexion contracture with minimal
      quadriceps activation but only reduced motion by 4.8 degrees  with maximal
      volitional quadriceps activation. CONCLUSIONS: Extension constraint knee braces
      alter joint alignment, dynamic balance, knee mechanics during gait, and vertical
      loading during gait. However, the changes in motion observed were lower than
      those induced by the constraining mechanism.

PMID- 24080448
TI  - Changes in intersegmental dynamics over time due to increased leg inertia.
AB  - The purpose of this study was to investigate the effects of asymmetrical loading
      on the intersegmental dynamics of the swing phase. Participants were asked to
      walk on a treadmill for 20min under three loading conditions: (a) unloaded
      baseline, (b) 2kg attached to the dominant limb's ankle, and (c) post-load,
      following load removal. Sagittal plane motion data of both legs were collected
      and an intersegmental dynamics analysis of each swing phase was performed.
      Comparisons of steady-state responses across load conditions showed that absolute
      angular impulses of the loaded limb's hip and knee increased significantly after
      load addition, and returned to baseline following load removal. Unloaded leg
      steady-state responses were not different across load conditions. However, after
      a change in leg inertia both legs experienced a period of adaptation that lasted
      approximately 40 strides before a steady state walking pattern was achieved.
      These findings suggest that the central nervous system refined the joint moments
      over time to account for the altered limb inertia and to maintain the underlying
      kinematic walking pattern. Maintaining a similar kinematic walking pattern
      resulted in altered moment profiles of the loaded leg, but similar moment
      profiles of the unloaded leg compared with the unloaded baseline condition. 

PMID- 24080449
TI  - The MAP(K) of fear: from memory consolidation to memory extinction.
AB  - The highly conserved mitogen-activated protein kinase/extracellular signal
      regulated kinase (MAPK/ERK) signaling cascade is involved in several
      intracellular processes ranging from cell differentiation to proliferation, as
      well as in synaptic plasticity. In the last two decades, the role of MAPK/ERK in
      long-term memory formation in mammals, particularly in fear-related memories, has
      been extensively investigated. In this review we describe knowledge advancement
      on the role of MAPK/ERK in orchestrating the intracellular processes that lead to
      the consolidation, reconsolidation and extinction of fear memories. In doing so,
      we report studies in which the specific role of MAP/ERK in switching from memory
      formation to memory erasure has been suggested. The possibility to target
      MAPK/ERK in developing and/or refining pharmacological approaches to treat
      psychiatric disorders in which fear regulation is defective has also been
      envisaged. 

PMID- 24080450
TI  - Effect of Sophora subprosrate polysaccharide on oxidative stress induced by PCV2
      infection in RAW264.7 cells.
AB  - In this study, an oxidative stress model was first developed in a mouse
      macrophage cell line (RAW264.7 cells) by infecting the cells with porcine
      circovirus type 2 (PCV2). The regulatory effect of Sophora subprosrate
      polysaccharide (SSP) on PCV2-induced oxidative stress was investigated. The
      results showed that after infection with PCV2, reactive oxygen species (ROS) and
      nitric oxide (NO) production, myeloperoxidase (MPO) activity, and inducible
      nitric oxide synthase (iNOS) expression were significantly increased. Meanwhile,
      the ratio of reduced glutathione to oxidized glutathione (GSH/GSSG) and hydroxyl
      radical prevention capacity were greatly reduced. These data indicate successful
      creation of an oxidative stress model in RAW264.7 cells. A dramatic decrease in
      cell viability was observed in the cells exposed to oxidative stress compared to
      the control. When the cells were treated with SSP in concentrations of 100, 200
      or 400 MUg/mL post PCV2 infection, an increase in the GSH/GSSG ratio and hydroxyl
      radical prevention capacity was observed. We also observed decreased ROS and NO
      production, MPO activity, and iNOS expression in the infected cells. Our results
      demonstrated that PCV2 infection was able to induce oxidative stress in RAW264.7
      cells and that SSP could reduce the negative effects resulting from the PCV2
      infection.

PMID- 24080451
TI  - Modeling and analysis of film composition on mechanical properties of maize
      starch based edible films.
AB  - The present study investigates the influence of composition (content of maize
      starch (1-3 g), sorbitol (0.5-1.0 ml), agar (0.5-1.0 g) and tween-80 (0.1-0.5
      ml)) on the mechanical properties (tensile strength, elongation, Young's modulus,
      puncture force and puncture deformation) of the maize starch based edible films
      using four factors with three level Box-Behnken design. The edible films were
      obtained by casting method. The results showed that, tween-80 increases the
      permeation of sorbitol in to the polymer matrix. Increasing concentration of
      sorbitol (hydrophilic nature and plasticizing effect of sorbitol) decreases the
      tensile strength, Young's modulus and puncture force of the films. The results
      were analyzed by Pareto analysis of variance (ANOVA) and second order polynomial
      models were obtained for all responses with high R(2) values (R(2)>0.95). 3D
      response surface plots were constructed to study the relationship between process
      variables and the responses.

PMID- 24080446
TI  - Genetic modifiers of menopausal hormone replacement therapy and breast cancer
      risk: a genome-wide interaction study.
AB  - Women using menopausal hormone therapy (MHT) are at increased risk of developing
      breast cancer (BC). To detect genetic modifiers of the association between
      current use of MHT and BC risk, we conducted a meta-analysis of four genome-wide
      case-only studies followed by replication in 11 case-control studies. We used a
      case-only design to assess interactions between single-nucleotide polymorphisms
      (SNPs) and current MHT use on risk of overall and lobular BC. The discovery stage
      included 2920 cases (541 lobular) from four genome-wide association studies. The
      top 1391 SNPs showing P values for interaction (Pint) <3.0 * 10(-3) were selected
      for replication using pooled case-control data from 11 studies of the Breast
      Cancer Association Consortium, including 7689 cases (676 lobular) and 9266
      controls. Fixed-effects meta-analysis was used to derive combined Pint. No SNP
      reached genome-wide significance in either the discovery or combined stage. We
      observed effect modification of current MHT use on overall BC risk by two SNPs on
      chr13 near POMP (combined Pint<=8.9 * 10(-6)), two SNPs in SLC25A21 (combined
      Pint<=4.8 * 10(-5)), and three SNPs in PLCG2 (combined Pint<=4.5 * 10(-5)). The
      association between lobular BC risk was potentially modified by one SNP in TMEFF2
      (combined Pint<=2.7 * 10(-5)), one SNP in CD80 (combined Pint<=8.2 * 10(-6)),
      three SNPs on chr17 near TMEM132E (combined Pint<=2.2*10(-6)), and two SNPs on
      chr18 near SLC25A52 (combined Pint<=4.6 * 10(-5)). In conclusion, polymorphisms
      in genes related to solute transportation in mitochondria, transmembrane
      signaling, and immune cell activation are potentially modifying BC risk
      associated with current use of MHT. These findings warrant replication in
      independent studies.

PMID- 24080452
TI  - Biocompatible conducting chitosan/polypyrrole-alginate composite scaffold for
      bone tissue engineering.
AB  - A polypyrrole based conducting scaffold was developed by incorporating
      polypyrrole-alginate (PPy-Alg) blend with chitosan using lyophilization technique
      and employed this composite as a substrate for bone tissue engineering. PPy-Alg
      blend was developed by oxidative chemical synthesis of polypyrrole using FeCl3 as
      oxidizing agent and characterized. The physiochemical characterization of the
      scaffold was done using SEM, FT-IR along with porosity measurement, swelling and
      in vitro degradation studies. Surface conductivity of the scaffolds was analyzed
      using Scanning Electrochemical microscopy (SECM). Results from cell viability and
      cell proliferation with MG-63 cells using Alamar blue assay confirmed the
      cytocompatible nature of the developed scaffold. In vitro biomineralization
      ability of the scaffold was assessed and thus the effectiveness of PPy
      Alg/chitosan scaffold in the field of tissue engineering was evaluated. 

PMID- 24080453
TI  - Studies on the interactions of bioactive quinone avarone and its methylamino
      derivatives with calf thymus DNA.
AB  - The interactions of avarone, a quinone from the marine sponge Dysideaavara, and
      the methylamino derivatives of avarone (2), 3'-(methylamino)avarone (3) and 4'
      (methylamino)avarone (4) with calf thymus DNA (CT-DNA) were studied. Agarose gel
      electrophoreticanalysis showed that binding of the quinones quenched fluorescence
      of ethidium bromide (EB). The extent of fluorescence quenching of intercalator EB
      by competitive displacement from EB-CT-DNA system and of groove binder Hoechst
      33258 (H) from H-CT-DNA system with the quinones was analyzed by fluorescence
      spectroscopy. The obtained results demonstrated that the quinones reduced binding
      of both the intercalator EB and the minor groove binder H, indicating possible
      degradation of DNA. The substituent on the quinone moiety determined the extent
      of DNA damaging effect of the quinone, which was the most extensive with 3'
      (methylamino)avarone and the least extensive with its regioisomer 4'
      (methylamino)avarone. The results were confirmed by the observed hyperchromic
      effects in UV-visible spectra measured after interactions of the derivatives with
      CT-DNA. 

PMID- 24080454
TI  - Leptin: a biomarker for sleep disorders?
AB  - Leptin, a pleiotropic protein hormone produced mainly by fat cells, regulates
      metabolic activity and many other physiological functions. The intrinsic
      circadian rhythm of blood leptin is modulated by gender, development, feeding,
      fasting, sleep, obesity, and endocrine disorders. Hyperleptinemia is implicated
      in leptin resistance. To determine the specificity and sensitivity of leptin
      concentrations in sleep disorders, we summarize here the alterations of leptin in
      four conditions in animal and human studies: short duration of sleep, sleep
      fragmentation, obstructive sleep apnea (OSA), and after use of continuous
      positive airway pressure (CPAP) to treat OSA. The presence and causes of
      contradictory findings are discussed. Though sustained insufficient sleep lowers
      fasting blood leptin and therefore probably contributes to increased appetite,
      obesity and OSA independently result in hyperleptinemia. Successful treatment of
      OSA by CPAP is predicted to decrease hyperleptinemia, making leptin an ancillary
      biomarker for treatment efficacy. Current controversies also call for
      translational studies to determine how sleep disorders regulate leptin
      homeostasis and how the information can be used to improve sleep treatment. 

PMID- 24080455
TI  - Epidemiology of oral human papillomavirus infection.
AB  - OBJECTIVE: To describe what is known about the epidemiology of oral human
      papillomavirus (HPV) infection. METHODS: In this article we review current data
      on HPV prevalence, natural history, mode of acquisition, and risk factors for
      oral HPV infection. RESULTS & CONCLUSION: Over the past several years new studies
      have informed our understanding of oral HPV infection. These data suggest oral
      HPV prevalence is higher in men than women and support the sexual transmission of
      HPV to the mouth by oral sex. Data is emerging suggesting that most oral HPV
      infections usually clear within a year on and describing risk factors for
      prevalent and persistent infection. Recent data support likely efficacy of the
      HPV vaccine for oral HPV, suggesting vaccination may reduce risk of HPV-related
      oropharyngeal cancer.

PMID- 24080456
TI  - Stability and change in symptoms, cognition, and community outcome in
      schizophrenia.
AB  - It has been well established that neurocognitive deficits are a core feature in
      schizophrenia and predict difficulties in functional independence. However, few
      studies have assessed the longitudinal stability of cognition and key aspects of
      functional outcome concurrently. Even less attention has been directed at the
      contingency of cognitive change on real world outcome changes. Accordingly, this
      study will assess the extent to which significant changes in cognition and
      community status are independent or related. As a point of comparison, the
      stability of clinical symptom status and the relationship between symptom and
      outcome change are evaluated. Symptoms, cognitive abilities, and community
      outcome was assessed in 128 patients with schizophrenia at baseline and again one
      year later. Intraclass correlation coefficients were used to index stability and
      reliable change index analyses quantified the prevalence of significant
      improvement or deterioration in each of the three illness features. Results from
      these analyses revealed that symptom status, cognitive functioning, and community
      outcome are similarly stable in treated schizophrenia outpatients. A small
      proportion of the sample demonstrated significant improvement or deterioration in
      these domains, with only weak evidence that such change was predicted by changes
      in symptoms or cognition. Further, there was no strong evidence of a preferential
      relationship for cognition relative to symptoms in relation to functional
      outcome. These results shed light on the strength and nature of the cognition
      real world outcome relationship in schizophrenia and have implications for
      pharmacological and behavioral interventions aimed at improving real world
      outcome. 

PMID- 24080458
TI  - Temporal trends of polychlorinated dibenzo-p-dioxins and dibenzofurans and dioxin
      like polychlorinated biphenyls in mothers' milk from Sweden, 1972-2011.
AB  - Temporal trends of polychlorinated dibenzo-p-dioxins (PCDDs), dibenzofurans
      (PCDFs) and dioxin-like polychlorinated biphenyls (DL-PCBs) in mothers' milk are
      still quite rare. Data are particularly scarce when it comes to concentrations
      from the last decade, 2000 and onwards. The aims of the present study were to
      assess temporal trends of PCDD, PCDF and DL-PCB in mothers' milk from Stockholm,
      1972-2011 and to compare the results with previous analysis of some of the older
      samples. The samples were analyzed by high resolution GC/MS and results were
      statistically evaluated for the periods, 1972-2011 and 2002-2011. The rate of
      which ?PCDDs, ?DL-PCBs and the ?TEQ are decreasing (on pg/g fat WHO-TEQ2005) is
      higher in the last decade compared to the 40year period, 1972-2011. A similar
      trend is indicated, but not confirmed, for ?TEQ of PCDFs, probably due to too
      many PCDF congeners below LOQ in the period 2002-2011. Concentrations of ?PCDDs,
      ?PCDFs, ?DLPCBs and ?TEQ, all expressed as pg/g fat on TEQ-WHO2005-basis, show a
      statistically significant decline over time, 5.8-6.8% per year, 1972-2011. The
      last ten years the annual declines for ?PCDDs, ?DL-PCBs and ?TEQ are 9.2-11% and
      for ?PCDF, 5.4%. Congener specific trend analysis, 2002-2001, of PCDDs and DL
      PCBs showed the same pattern, while the PCDF congeners showed no such general
      trend. The results from the re-analysis showed good agreement with slightly lower
      ?TEQ1998 pg/g fat concentrations in six out of seven samples and mean difference
      of 13% in ?TEQ1998. The study shows that time series can be elongated from
      previous studies, as long as the sample population remains the same. 

PMID- 24080457
TI  - Molecular classification, pathway addiction, and therapeutic targeting in diffuse
      large B cell lymphoma.
AB  - The rapid emergence of molecularly based techniques to detect changes in the
      genetic landscape of diffuse large B cell lymphoma (DLBCL), including gene
      expression, DNA and RNA sequencing, and epigenetic profiling, has significantly
      influenced the understanding and therapeutic targeting of DLBCL. In this review,
      we briefly discuss the new methods used in the study of DLBCL. We describe the
      influence of the generated data on DLBCL classification and the identification of
      new entities and altered cell survival strategies, with a focus on the renewed
      interest in some classic oncogenic pathways that are currently targeted for new
      therapy. Finally, we examine the molecular genomic studies that revealed the
      importance of the tumor microenvironment in the pathogenesis of DLBCL. 

PMID- 24080459
TI  - New route to the 5-((arylthio- and heteroarylthio)methylene)-3-(2,2,2
      trifluoroethyl)-furan-2(5H)-ones--key intermediates in the synthesis of 4
      aminoquinoline gamma-lactams as potent antimalarial compounds.
AB  - In this Letter we report on a multi-step synthesis of 5-((arylthio- and
      heteroarylthio)-methylene)-3-(2,2,2-trifluoroethyl)furan-2(5H)-ones starting from
      gamma-keto thiolester or gamma-keto carboxylic acid. The key intermediate gamma
      lactones were then reacted with 4-aminoquinoline-derived amines via ring opening
      ring closure (RORC) process affording the corresponding gamma-hydroxy-gamma
      lactams in moderate to good yields. In vitro antimalarial activity of the
      resulting new 4-aminoquinoline gamma-lactams were evaluated against Plasmodium
      falciparum clones of variable sensitivity (3D7 and W2) and were found to be
      active in the range of 89-1600 nM with good resistance index and did not show
      cytotoxicity in vitro when tested against human umbilical vein endothelial cells
      (HUVEC) up to concentration of 50 MUM.

PMID- 24080460
TI  - Serendipity in drug-discovery: a new series of 2-(benzyloxy)benzamides as TRPM8
      antagonists.
AB  - A new series of 2-(benzyloxy)benzamides are presented that are potent functional
      antagonists of TRPM8 and possess improved LipE and LE compared to the original
      lead. They were discovered through a series of compound libraries and we present
      a powerful visualization method for the chemical space explored with each
      library. Remarkably this new series originated from the highest risk design
      strategy where compounds were synthesised with the least degree of similarity to
      the lead structure. 

PMID- 24080462
TI  - Towards boron neutron capture therapy: the formulation and preliminary in vitro
      evaluation of liposomal vehicles for the therapeutic delivery of the dequalinium
      salt of bis-nido-carborane.
AB  - Liposomes of phosphatidylcholine or of dimyristoylphosphatidylcholine that
      incorporate bis-nido-carborane dequalinium salt are stable in physiologically
      relevant media and have in vitro toxicity profiles that appear to be compatible
      with potential therapeutic applications. These features render the structures
      suitable candidate boron-delivery vehicles for evaluation in the boron neutron
      capture therapy of cancer. 

PMID- 24080461
TI  - Discovery of N-(benzo[1,2,3]triazol-1-yl)-N-(benzyl)acetamido)phenyl)
      carboxamides as severe acute respiratory syndrome coronavirus (SARS-CoV) 3CLpro
      inhibitors: identification of ML300 and noncovalent nanomolar inhibitors with an
      induced-fit binding.
AB  - Herein we report the discovery and SAR of a novel series of SARS-CoV 3CLpro
      inhibitors identified through the NIH Molecular Libraries Probe Production
      Centers Network (MLPCN). In addition to ML188, ML300 represents the second probe
      declared for 3CLpro from this collaborative effort. The X-ray structure of SARS
      CoV 3CLpro bound with a ML300 analog highlights a unique induced-fit
      reorganization of the S2-S4 binding pockets leading to the first sub-micromolar
      noncovalent 3CLpro inhibitors retaining a single amide bond. 

PMID- 24080463
TI  - Restraining the flexibility of the central linker in terameprocol results in
      constrained analogs with improved growth inhibitory activity.
AB  - The semi-synthetic lignan terameprocol inhibits the transcription of several
      inflammatory and oncogenic genes and has been evaluated for its anti-cancer
      properties. Here we investigated the effect of restricting the flexibility of the
      carbon linker connecting the terminal rings of terameprocol on its growth
      inhibitory activity. Conformational restriction was explored by introducing
      unsaturation, inserting polar entities with limited flexibility and cyclization
      of the connecting linker. Twenty three compounds were synthesized and evaluated
      on a panel of malignant human cells. The most promising compounds were those with
      non-polar linkers, as seen in butadiene 1a and the cyclized benzylideneindane
      analog 7. Both compounds were more potent than terameprocol on pancreatic BxPC-3
      cells with GI50 values of 3.4 and 8.1 MUM, respectively. Selected isomers of 1a
      (E,E) and 7 (Z) adopted low energy bent conformations that mimicked the low
      energy conformer of terameprocol. It is tempting to propose that conformational
      similarity to terameprocol may have contributed to their good activity. The
      scaffolds of 1a and 7 should be further investigated for their anticancer
      potential.

PMID- 24080464
TI  - Elevated serum ubiquitin C-terminal hydrolase-L1 levels in patients with carbon
      monoxide poisoning.
AB  - OBJECTIVE: Ubiquitin C-terminal hydrolase-L1 (UCH-L1) has been established as a
      reliable and potential biomarker of neuronal damage after acute neurologic
      insults, such as ischemic stroke, subarachnoid hemorrhage, and traumatic brain
      injury. However, the effect of serum UCH-L1 levels has not been investigated in
      carbon monoxide (CO)-poisoned patients. The aim of the present study was to
      evaluate whether serum UCH-L1 levels are a reliable marker of brain damage and
      the association of UCH-L1 with outcome. DESIGN AND METHODS: This case-control
      study enrolled 46 CO-poisoned subjects and 30 controls. Using an enzyme-linked
      immunosorbent assay (ELISA) kit, we studied the temporal profile of serum UCH-L1
      levels at 6, 12, 24 and 48 h after acute CO poisoning. Poisoning severity was
      assessed using the Glasgow Coma Scale (GCS) score. Long-term outcome was assessed
      using the Glasgow Outcome Scale (GOS) at 6 months after poisoning. RESULTS:
      Compared with controls, CO-poisoned patients had significantly elevated serum
      levels of UCH-L1 at each time point after poisoning. There were significantly
      higher levels of UCH-L1 in CO-poisoned patients with a lower GCS score as well as
      in those with a poor 6-month outcome dichotomized GOS. CONCLUSIONS: Serum levels
      of UCH-L1 appear to have potential clinical utility in providing valuable
      information about poisoning severity and outcome after CO poisoning.

PMID- 24080465
TI  - Spectrum of beta-thalassemia mutations in Guizhou Province, PR China, including
      first observation of codon 121 (GAA>TAA) in Chinese population.
AB  - OBJECTIVES: Although the population prevalence and mutation spectrum of beta
      thalassemia in most areas of south China have been characterized, the mutations
      have not been elucidated in Guizhou Province. The aim of this study was to
      investigate the spectrum of beta-thalassemia in this province. DESIGN AND
      METHODS: We detected and analyzed beta-globin gene mutations in 407 beta
      thalassemia patients and carriers by PCR-based reverse dot blot (RBD) and direct
      sequencing methods. RESULTS: Twelve types of beta-globin gene mutations were
      detected. Among the 12 different mutations, six mutations are common, accounting
      for 97% of mutated alleles. The most prevalent mutation is codon 17 (A->T) with
      an allele frequency of 40.7%. In addition, codon 121 (GAA>TAA), a rare dominant
      mutation, was detected in a patient with beta-thalassemia intermedia for the
      first time in China. CONCLUSIONS: The results of this study will be useful in
      genetic counseling and prenatal diagnostic service of beta-thalassemia in Guizhou
      Province.

PMID- 24080466
TI  - Cranial compression using distractors in reverse fashion as an alternative method
      for correcting scaphocephaly in older patients.
AB  - BACKGROUND: Intraoperative calvarial contraction of conventional calvarial
      remodeling is more difficult in scaphocephaly patients who are 1 year or older in
      age. In our current study, gradual cranial compression with a distractor was used
      to correct scaphocephaly in this older age group and the surgical results were
      quantitatively analyzed. METHODS: Gradual cranial compression was used to treat 7
      sagittal craniosynostosis patients. The mean age was 20.9 months (range, 12-32
      months) and the mean follow-up period was 65 months (range, 3-81 months).
      Computed tomography was used to calculate the cephalic index (CI; equal to the
      maximum width of the head/maximum length of the head *100), and the ratios of
      these indices at 3 different time periods (before, immediately after, and at 1
      year postoperatively) were evaluated. RESULTS: An average cranial compression of
      18 mm was found to be possible with an average CI increase from 67.9 to 73.5. The
      CI ratio at 1 year after surgery was found to be the highest, showing a 9.8%
      increase. CONCLUSION: Sagittal craniosynostosis patients are less easy to treat
      with conventional calvarial remodeling surgery if they are older than 1 year.
      Gradual cranial vault compression with distractors can be another option in these
      cases.

PMID- 24080467
TI  - Bioisosteric approach in designing new monastrol derivatives: an investigation on
      their ADMET prediction using in silico derived parameters.
AB  - Medicinal chemists are facing an increasing challenge to deliver safer and more
      effective medicines. An appropriate balance between drug-like properties such as
      solubility, permeability, metabolic stability, efficacy and toxicity is one of
      the most challenging problems during lead optimization of a potential drug
      candidate. Insoluble and impermeable compounds can result in erroneous biological
      data and unreliable SAR in enzyme and cell-based assays. The weak inhibitory
      activity and non-drug-like properties of monastrol, the first small mitotic
      kinesin Eg5 inhibitor, has hampered its further development. In this
      investigation, a bioisosteric approach was applied that resulted in the
      replacement of C-5 carbonyl of monastrol with thio-carbonyl. Further lead
      optimization of drug-like properties was evaluated through in silico predictions
      by using ADMET predictor software. This minor structural modification resulted in
      upgraded human effective jejunal permeability (Peff) and improved permeability in
      Madin-Darby canine kidney (MDCK) cells. Furthermore, C-5 thiocarbonyl analogue of
      monastrol (named as Special-2) was found safe to administer orally with no
      phospholipidosis toxicity, no raised levels of serum glutamate oxaloacetate
      transaminase (SGOT) and no potential towards cardiotoxicity. Molecular docking
      study was also carried out to understand the binding modes of these compounds.
      The docking study showed high binding affinity of the designed compounds against
      KSP. Hence a combination of in silico ADMET studies and molecular docking can
      help to improve prediction success and these compounds might be act as potential
      candidate for KSP inhibition. 

PMID- 24080468
TI  - Rosmarinus officinalis L. leaf extract improves memory impairment and affects
      acetylcholinesterase and butyrylcholinesterase activities in rat brain.
AB  - Rosmarinus officinalis L. leaf as part of a diet and medication can be a valuable
      proposal for the prevention and treatment of dementia. The aim of the study was
      to assess the effects of subchronic (28-fold) administration of a plant extract
      (RE) (200 mg/kg, p.o.) on behavioral and cognitive responses of rats linked with
      acetylcholinesterase (AChE) and butyrylcholinesterase (BuChE) activity and their
      mRNA expression level in the hippocampus and frontal cortex. The passive
      avoidance test results showed that RE improved long-term memory in scopolamine
      induced rats. The extract inhibited the AChE activity and showed a stimulatory
      effect on BuChE in both parts of rat brain. Moreover, RE produced a lower mRNA
      BuChE expression in the cortex and simultaneously an increase in the hippocampus.
      The study suggests that RE led to improved long-term memory in rats, which can be
      partially explained by its inhibition of AChE activity in rat brain.

PMID- 24080469
TI  - Interactions between Mytilus galloprovincialis hemocytes and the bivalve
      pathogens Vibrio aestuarianus 01/032 and Vibrio splendidus LGP32.
AB  - Marine bivalves can accumulate large numbers of bacteria, in particular Vibrio
      species, whose persistence in bivalve tissues largely depends on their
      sensitivity to the bactericidal activity of circulating hemocytes and hemolymph
      soluble factors. The interactions between vibrios and hemolymph have been
      investigated, in particular in bivalve species susceptible to infection by
      certain Vibrio spp. and strains. In this work, the effects of two bivalve
      pathogens, Vibrio splendidus LGP32 (V.s.) and Vibrio aestuarianus 01/032 (V.a.),
      isolated from oyster mortality outbreaks, on the hemocytes of Mytilus
      galloprovincialis were investigated. In vitro, V.s., but not V.a., induced a
      dramatic decrease in lysosomal membrane stability-LMS in the hemocytes; both
      vibrios induced a moderate lysozyme release, with V.s. > V.a.. The V.s.-induced
      decrease in LMS was mediated by activation of PI-3Kinase, as shown by use of
      different kinase inhibitors. TEM analysis showed rapid internalization of both
      vibrios; however, V.s. lead to cellular and lysosomal damage and was able to
      survive within the hemocytes, whereas significant killing of V.a. was observed.
      In vivo, in mussels challenged with either vibrio and sampled at 6, 24 and 96 h
      post-injection, transient decreases in hemocyte LMS and progressive increases in
      serum lysozyme activity were observed, with V.s. > V.a.. Moreover, whereas V.a.
      was efficiently cleared from hemolymph, V.s. showed significant growth, that was
      maximal at 24 h p.i. when lowest LMS values were recorded in the hemocytes. Both
      vibrios also induced significant decreases in LMS in the digestive gland, again
      with V.s. > V.a.. The results indicate distinct interactions between mussel
      hemocytes and the two vibrio strains tested. The effects of V.s. may be due to
      the capacity of this strain to interfere with the signaling pathways involved in
      hemocyte function, thus escaping the bactericidal activity of the host cell, as
      observed for certain mammalian pathogens. Although V.s. is considered not
      pathogenic to Mytilus, this vibrio strain can affect the lysosomal function at
      the cellular and tissue level, thus leading to stressful conditions.

PMID- 24080470
TI  - Identification of immune-related SNPs in the transcriptome of Mytilus chilensis
      through high-throughput sequencing.
AB  - Single nucleotide polymorphisms (SNPs) identified in coding regions represent a
      useful tool for understanding the immune response against pathogens and stressful
      environmental conditions. In this study, a SNPs database was generated from
      transcripts involved in the innate immune response of the mussel Mytilus
      chilensis. The SNPs were identified through hemocytes transcriptome sequencing
      from 18 individuals, and SNPs mining was performed in 225,336 contigs, yielding
      20,306 polymorphisms associated to immune-related genes. Classification of
      identified SNPs was based on different pathways of the immune response for
      Mytilus sp. A total of 28 SNPs were identified in the Toll-like receptor pathway
      and included 5 non-synonymous polymorphisms; 19 SNPs were identified in the
      apoptosis pathway and included 3 non-synonymous polymorphisms; 35 SNPs were
      identified in the Ubiquitin-mediated proteolysis pathway and included 4 non
      synonymous variants; and 54 SNPs involved in other molecular functions related to
      the immune response, such as molecular chaperones, antimicrobial peptides, and
      genes that interacts with marine toxins were also identified. The molecular
      markers identified in this work could be useful for novel studies, such as those
      related to associations between high-resolution molecular markers and functional
      response to pathogen agents. 

PMID- 24080472
TI  - Bilingualism beyond languages: the impact of bilingualism upon the brain: comment
      on "The bilingual brain: flexibility and control in the human cortex" by
      Buchweitz and Prat.

PMID- 24080471
TI  - Existing and potential therapeutic uses for N-acetylcysteine: the need for
      conversion to intracellular glutathione for antioxidant benefits.
AB  - N-acetyl-l-cysteine (NAC) has long been used therapeutically for the treatment of
      acetaminophen (paracetamol) overdose, acting as a precursor for the substrate (l
      cysteine) in synthesis of hepatic glutathione (GSH) depleted through drug
      conjugation. Other therapeutic uses of NAC have also emerged, including the
      alleviation of clinical symptoms of cystic fibrosis through cysteine-mediated
      disruption of disulfide cross-bridges in the glycoprotein matrix in mucus. More
      recently, however, a wide range of clinical studies have reported on the use of
      NAC as an antioxidant, most notably in the protection against contrast-induced
      nephropathy and thrombosis. The results from these studies are conflicting and a
      consensus is yet to be reached regarding the merits or otherwise of NAC in the
      antioxidant setting. This review seeks to re-evaluate the mechanism of action of
      NAC as a precursor for GSH synthesis in the context of its activity as an
      "antioxidant". Results from recent studies are examined to establish whether the
      pre-requisites for effective NAC-induced antioxidant activity (i.e. GSH depletion
      and the presence of functional metabolic pathways for conversion of NAC to GSH)
      have received adequate consideration in the interpretation of the data. A key
      conclusion is a reinforcement of the concept that NAC should not be considered to
      be a powerful antioxidant in its own right: its strength is the targeted
      replenishment of GSH in deficient cells and it is likely to be ineffective in
      cells replete in GSH. 

PMID- 24080473
TI  - Preventing childhood falls within the home: overview of systematic reviews and a
      systematic review of primary studies.
AB  - In most countries falls are the most common medically attended childhood injury
      and the majority of injuries in pre-school children occur at home. Numerous
      systematic reviews have reviewed evidence of the effectiveness of falls
      prevention interventions, but this evidence has not been synthesised into an
      overview, making it difficult for policy makers and practitioners to easily
      access the evidence. To synthesise all available evidence, we conducted an
      overview of reviews of home safety interventions targeting childhood falls,
      extracted data from primary studies included in the reviews and supplemented this
      with a systematic review of primary studies published subsequent to the reviews.
      Bibliographic databases, websites, conference proceedings, journals and
      bibliographies of included studies were searched for systematic reviews of
      studies with experimental or controlled observational designs. Thirteen reviews
      were identified containing 24 primary studies. Searches for additional primary
      studies identified five further studies not included in reviews. Evidence of the
      effect of interventions on falls or fall injuries was sparse, with only one of
      three primary studies reporting this outcome finding a reduction in falls.
      Interventions were effective in promoting the use of safety gates and furniture
      corner covers. There was some evidence of a reduction in baby walker use. The
      effect on the use of window safety devices, non-slip bath mats/decals and the
      reduction of tripping hazards was mixed. There was limited evidence that
      interventions were effective in improving lighting in corridors, altering
      furniture layout and restricting access to roofs. Most interventions to prevent
      childhood falls at home have not been evaluated in terms of their effect on
      reducing falls. Policy makers and practitioners should promote use of safety
      gates and furniture covers and restriction of baby walker use. Further research
      evaluating the effect of interventions to reduce falls and falls-related injuries
      is urgently required. 

PMID- 24080474
TI  - Updates on the model and the evolution of cytokinin signaling.
AB  - Cytokinins represent a class of phytohormones, which are key players not only in
      many processes important for plant growth and development, but also in the
      response to changes in their environment. The model for the cytokinin signaling
      pathway was established at the turn of the last century and many experiments
      confirmed its validity. In recent years several changes and extensions to the
      model were necessary to accommodate new findings concerning its components, such
      as subcellular localization, selective protein degradation and new modes of cross
      talk. In addition phylogenetic analyses of components of the cytokinin circuitry
      started to reveal the origin and evolution of the cytokinin regulatory system. 

PMID- 24080475
TI  - Leishmaniasis causes oxidative stress and alteration of oxidative metabolism and
      viability of neutrophils in dogs.
AB  - The aim of the present study was to test the hypothesis that oxidative stress and
      alteration of oxidative metabolism and apoptosis of neutrophils in dogs vary with
      the stage of leishmaniasis and to determine the contribution of uremia to such
      alterations. Dogs with leishmaniasis were classified into two stages: moderate
      (Leish II, n=20) or very severe (i.e. with concurrent uremia; Leish IV, n=20)
      according to the LeishVet Consensus. The two leishmaniasis groups were compared
      with uremic dogs without leishmaniasis (Uremic, n=10) and to healthy dogs
      (Control, n=30). To determine oxidative stress, total antioxidant/oxidant
      capacity, lipid peroxidation, total glutathione and the plasma antioxidants
      albumin, uric acid and bilirubin were quantified. Superoxide production was
      determined using the hydroethidine probe and viability and apoptosis were
      measured using annexin V-PE by capillary flow cytometry. Oxidative stress was
      present in both uremia and leishmaniasis with reduced total antioxidant capacity
      and was associated with increased induced production of superoxide and apoptosis.
      The greatest amount of oxidants was observed in animals with moderate disease
      only. Neutrophils from uremic dogs with and without leishmaniasis had decreased
      viability and an increased apoptosis rate in addition to increased lipid
      peroxidation. In conclusion, oxidative stress occurs in both stages of
      leishmaniasis with differences in intensity and levels of plasma markers;
      however, uremia does contribute to the decreased spontaneous viability of
      neutrophils in dogs in the final stage of the disease. 

PMID- 24080476
TI  - Expression of purinergic P2X receptor subtypes 1, 2, 3 and 7 in equine laminitis.
AB  - Tissue sensitisation and chronic pain have been described in chronic-active
      laminitis in the horse, making treatment of such cases difficult. Purinergic P2X
      receptors are linked to chronic pain and inflammation. The aim of this study was
      to examine the expression of purinergic P2X receptor subtypes 1, 2, 3 and 7 in
      the hoof, palmar digital vessels and nerve, dorsal root ganglia and spinal cord
      in horses with chronic-active laminitis (n=5) compared to non-laminitic horses
      (n=5). Immunohistochemical analysis was performed on tissue sections using
      antibodies against P2X receptor subtypes 1-3 and 7. In horses with laminitis,
      there was a reduction in the thickness of the tunica media layer of the palmar
      digital vein as a proportion of the whole vessel diameter (0.48+/-0.05) compared
      to the non-laminitic group (0.57+/-0.04; P=0.02). P2X receptor subtype 3 was
      expressed in the smooth muscle layer (tunica media) of the palmar digital artery
      of horses with laminitis, but was absent in horses without laminitis. There was
      strong expression of P2X receptor subtype 7 in the proliferating, partially
      keratinised, epidermal cells of the secondary epidermal lamellae in the hooves of
      horses with laminitis, but no immunopositivity in horses without laminitis. 

PMID- 24080478
TI  - Inadequate monitoring in advanced stages of disease with lack of supportive
      counseling increases attrition among patients on antiretroviral treatment at a
      large urban clinic in Uganda.
AB  - BACKGROUND: The purpose of this case-control study was to identify risk factors
      for loss to follow-up (LTFU). METHODS: Cases and controls were selected from HIV
      positive patients, aged 18 years and older, on antiretroviral therapy (ART) at
      the Infectious Diseases Clinic (IDC) in January 2008. As cases, we selected 209
      patients who in 2008 did not return to the clinic within 90 days of their
      scheduled appointment date. As controls, we randomly selected 626 patients from
      the 5872 patients who were following up at the end of December 2008. RESULTS: In
      multivariable logistic regression analysis, urban or semiurban residence, World
      Health Organization disease stage III or IV at ART initiation, a median CD4 count
      at last visit <200 cells/mm(3), tuberculosis (TB) in the 6 months before the last
      visit, absence of counseling before ART initiation, and no disclosure of HIV
      status were associated with LTFU. CONCLUSION: This study demonstrates the
      importance of close patient monitoring in advanced stages of disease, supportive
      counseling for patients initiating ART, extra psychosocial support for patients
      with TB and HIV coinfection, assisting patients with disclosure, and setting up a
      good referral system to retain patients on ART.

PMID- 24080477
TI  - Neutropenia in HIV-Infected Kenyan Women Receiving Triple Antiretroviral
      Prophylaxis to Prevent Mother-to-Child HIV Transmission Is Not Associated with
      Serious Clinical Sequelae.
AB  - BACKGROUND: Absolute neutrophil counts (ANCs) are lower in East African adults.
      To assess the impact of lower ANCs, we reviewed data from HIV-infected Kenyan
      women receiving antiretroviral therapy antepartum and postpartum. METHODS: The
      Kisumu Breastfeeding Study (KiBS) participants received an antiretroviral regimen
      from 34 weeks' gestation through 6 months postpartum. Measured ANCs and
      subsequent illnesses were reviewed. Adverse events (AEs) potentially attributable
      to neutropenia were identified, and ANCs were graded using the 2004 Division of
      AIDS table for Grading the Severity of AEs. RESULTS: Among 478 women with >=1
      postpartum ANC measured, 298 (62.1%) women met criteria for an AE (<1.3 * 10(9)
      cells/L). Of those, 38 (12.5%) women experienced a nonlife-threatening illness
      potentially attributable to neutropenia. CONCLUSION: More than half of KiBS women
      met criteria for neutropenia. The mild clinical experience of most participants
      with low ANCs supports that these values might be typical for this population and
      may not result in adverse clinical sequelae.

PMID- 24080479
TI  - Activity and interactions of levofloxacin, linezolid, ethambutol and amikacin in
      three-drug combinations against Mycobacterium tuberculosis isolates in a human
      macrophage model.
AB  - Multidrug resistance is a problem in the management of tuberculosis, creating an
      urgent need for new regimens including currently available drugs. Macrophage
      models allow an evaluation of the effect of drugs against intracellular bacilli.
      The effect of the following different drug combinations against six multidrug
      resistant and six drug-susceptible clinical isolates of Mycobacterium
      tuberculosis multiplying inside the human macrophage THP-1 cell line was studied:
      levofloxacin/linezolid/ethambutol; levofloxacin/amikacin/ethambutol; and
      levofloxacin/linezolid/amikacin. Macrophages were lysed, seeded onto Middlebrook
      7H11 plates and CFU were counted after 21 days of incubation. The interaction of
      the drugs in combination was interpreted by the effect of the combination
      compared with the most active single drug alone. The antimicrobial activity of
      the drugs was evaluated comparing the log(10)CFU/well of the isolate with and
      without the drug. Drug concentrations within infected macrophages and in
      extracellular medium were simultaneously determined by chromatography. The
      levofloxacin/linezolid/amikacin and levofloxacin/linezolid/ethambutol
      combinations showed antagonism against most of the isolates (91.7%) after a 4-day
      protocol, whereas levofloxacin/amikacin/ethambutol displayed indifference.
      Levofloxacin alone and levofloxacin/amikacin/ethambutol were the most potent
      antimicrobials, presenting reductions up to 5.49 log(10) and 5.86 log(10),
      respectively. The drug penetration percentages ranged from 5.46% to 11.10%.
      Intracellular concentrations for the drug alone compared with those for the drugs
      in combination were not significantly different. All of the combinations tested
      against M. tuberculosis-infected macrophages showed antimicrobial activity, with
      combinations including linezolid and levofloxacin showing an antagonistic effect
      that may be explained by efflux transporters or changes in the macrophage
      environment.

PMID- 24080480
TI  - Antiproliferative activity of Pt(IV)-bis(carboxylato) conjugates on malignant
      pleural mesothelioma cells.
AB  - The bifunctional Pt(IV) conjugate cis,cis,trans
      diamminedichloridobis(valproato)platinum(IV), based on the cisplatin square-plane
      with two axial valproato (2-propylpentanoate, VPA) ligands, has been re
      synthesized with a modified procedure and its biological activity was compared
      with that of its isomer cis,cis,trans-diamminedichloridobis(n
      octanoato)platinum(IV). Both complexes showed a striking cytotoxic effect (in the
      micro or sub-micromolar range) on various human carcinoma cell lines (namely
      ovarian, colon, breast and lung cancer), and, in particular, on cells derived
      from malignant pleural mesothelioma. This remarkable activity is due to the
      action of the cisplatin metabolite only, generated by the intracellular Pt(IV)
      >Pt(II) reduction, which concentration is greatly increased by the enhanced
      cellular accumulation of the original, highly lipophilic Pt(IV)-bis(carboxylato)
      complexes. The two axial VPA ligands are released in a too low concentration to
      act as histone deacetylase inhibitor (HDACI), as VPA works in the millimolar
      range, so that no synergism can be claimed. Moreover, n-octanoic acid is
      substantially deprived of any HDACI propensity. 

PMID- 24080481
TI  - Genome-wide analysis of the heat stress response in Zebu (Sahiwal) cattle.
AB  - Environmental-induced hyperthermia compromises animal production with drastic
      economic consequences to global animal agriculture and jeopardizes animal
      welfare. Heat stress is a major stressor that occurs as a result of an imbalance
      between heat production within the body and its dissipation and it affects
      animals at cellular, molecular and ecological levels. The molecular mechanism
      underlying the physiology of heat stress in the cattle remains undefined. The
      present study sought to evaluate mRNA expression profiles in the cattle blood in
      response to heat stress. In this study we report the genes that were
      differentially expressed in response to heat stress using global scale genome
      expression technology (Microarray). Four Sahiwal heifers were exposed to 42
      degrees C with 90% humidity for 4h followed by normothermia. Gene expression
      changes include activation of heat shock transcription factor 1 (HSF1), increased
      expression of heat shock proteins (HSP) and decreased expression and synthesis of
      other proteins, immune system activation via extracellular secretion of HSP. A
      cDNA microarray analysis found 140 transcripts to be up-regulated and 77 down
      regulated in the cattle blood after heat treatment (P<0.05). But still a
      comprehensive explanation for the direction of fold change and the specific genes
      involved in response to acute heat stress still remains to be explored. These
      findings may provide insights into the underlying mechanism of physiology of heat
      stress in cattle. Understanding the biology and mechanisms of heat stress is
      critical to developing approaches to ameliorate current production issues for
      improving animal performance and agriculture economics. 

PMID- 24080482
TI  - Interstitial 2q24.3 deletion including SCN2A and SCN3A genes in a patient with
      autistic features, psychomotor delay, microcephaly and no history of seizures.
AB  - Mutations in neuronal voltage-gated sodium channel genes SCN1A, SCN2A, and SCN3A
      may play an important role in the etiology of neurological diseases and
      psychiatric disorders, besides various types of epilepsy. Here we describe a 3
      year-old boy with autistic features, language delay, microcephaly and no history
      of seizures. Array-CGH analysis revealed an interstitial deletion of ~291.9kB at
      band 2q24.3 disrupting the entire SCN2A gene and part of SCN3A. We discuss the
      effects of haploinsufficiency of SCN2A and SCN3A on the genetic basis of
      neurodevelopmental and neurobehavioral disorders and we propose that this
      haploinsufficiency may be associated not only with epilepsy, but also with
      autistic features.

PMID- 24080483
TI  - Telomere lengths at birth in trisomies 18 and 21 measured by Q-FISH.
AB  - Trisomies 18 and 21 are genetic disorders in which cells possess an extra copy of
      each of the relevant chromosomes. Individuals with these disorders who survive
      birth generally have a shortened life expectancy. As telomeres are known to play
      an important role in the maintenance of genomic integrity by protecting the
      chromosomal ends, we conducted a study to determine whether there are differences
      in telomere length at birth between individuals with trisomy and diploidy, and
      between trisomic chromosomes and normal chromosomes. We examined samples of
      peripheral blood lymphocytes (PBLs) from 31 live neonates (diploidy: 10, trisomy
      18: 10, trisomy 21: 11) and estimated the telomere length of each chromosome arm
      using Q-FISH. We observed that the telomeres of trisomic chromosomes were neither
      shorter nor longer than the mean telomere length of chromosomes as a whole among
      subjects with trisomies 18 and 21 (intra-cell comparison), and we were unable to
      conclude that there were differences in telomere length between 18 trisomy and
      diploid subjects, or between 21 trisomy and diploid subjects (inter-individual
      comparison). Although it has been reported that telomeres are shorter in older
      individuals with trisomy 21 and show accelerated telomere shortening with age,
      our data suggest that patients with trisomies 18 and 21 may have comparably sized
      telomeres. Therefore, it would be advisable for them to avoid lifestyle habits
      and characteristics such as obesity, cigarette smoking, chronic stress, and
      alcohol intake, which lead to marked telomere shortening. 

PMID- 24080484
TI  - Characterization of a novel growth hormone receptor-encoding cDNA in rainbow
      trout and regulation of its expression by nutritional state.
AB  - To clarify the divergence of the growth hormone receptor (GHR) family, we
      characterized a novel GHR from a teleost fish (rainbow trout). A 2357-nt cDNA was
      isolated and found to contain a single initiation site 71 nt from the most 5'
      end, an open reading frame of 1971 nt encoding a 657-amino acid protein, and a
      single polyadenylation site 229 nt from the poly-A tail. Based on structural
      analysis, the protein was identified as a type 1 GHR (GHR1). The new GHR1 shares
      42% and 43% amino acid identity, respectively, with GHR2a and GHR2b, the two type
      2 GHRs isolated from trout previously. GHR1 mRNA was found in a wide array of
      tissues with the highest expression in the liver, red muscle, and white muscle.
      Fasting animals for 4 weeks reduced steady state levels of GHR1 in the liver,
      adipose, and red muscle. These findings help clarify the divergence and
      nomenclature of GHRs and provide insight into the function of duplicated GHR
      types.

PMID- 24080486
TI  - Familial progressive supranuclear palsy: a literature review.
AB  - BACKGROUND: Many genes/loci associated with Parkinsonian disorders have been
      identified. However, the genetic causes for a number of familial forms of
      Parkinsonian disorders remain to be elucidated. OBJECTIVE: It was the aim of this
      paper to review the familial progressive supranuclear palsy (PSP) cases without
      any known gene mutations published in the English literature. METHODS: We
      searched the PubMed database for reports of familial PSP cases without known
      mutations. RESULTS: We found 19 PSP families. The mean age at onset was
      approximately 60 years, and the mean disease duration was about 8 years.
      Parkinsonism and ophthalmoplegia were most frequently reported, and a vast
      majority of patients manifested with these two symptoms. Other symptoms such as
      falls, postural instability and pyramidal signs were also common. A small subset
      of patients transiently responded to L-dopa therapy. CONCLUSION: There is an
      increasing number of reported familial PSP. A recently performed genome-wide
      association study indicated genetic factors for this condition. Furthermore,
      clinical, pathological and genetic investigations will open new avenues to the
      discovery of causative genes and new therapeutics for PSP.

PMID- 24080485
TI  - MRNA and miRNA expression patterns associated to pathways linked to metal mixture
      health effects.
AB  - Metals are a threat to human health by increasing disease risk. Experimental data
      have linked altered miRNA expression with exposure to some metals. MiRNAs
      comprise a large family of non-coding single-stranded molecules that primarily
      function to negatively regulate gene expression post-transcriptionally. Although
      several human populations are exposed to low concentrations of As, Cd and Pb as a
      mixture, most toxicology research focuses on the individual effects that these
      metals exert. Thus, this study aims to evaluate global miRNA and mRNA expression
      changes induced by a metal mixture containing NaAsO2, CdCl2, Pb(C2H3O2)2.3H2O and
      to predict possible metal-associated disease development under these conditions.
      Our results show that this metal mixture results in a miRNA expression profile
      that may be responsible for the mRNA expression changes observed under
      experimental conditions in which coding proteins are involved in cellular
      processes, including cell death, growth and proliferation related to the metal
      associated inflammatory response and cancer. 

PMID- 24080487
TI  - New possibilities to exploit the potentiality of cord blood cells in the context
      of transplantation.

PMID- 24080489
TI  - Rabbit morula vitrification reduces early foetal growth and increases losses
      throughout gestation.
AB  - Several studies have extensively examined structural and biochemical damage
      induced by cryopreservation that may lead to loss of rabbit embryo viability, but
      very little information is available on alterations in growth during gestation
      and at gene expression level. We started our work by comparing the distribution
      of losses of embryo and foetal development between control and vitrified rabbit
      morulae. Furthermore, data on foetal sack, foetal and maternal placenta and
      foetus size for 10-14 days of gestation were evaluated by ultrasonography. We
      reported that vitrification procedure causes detrimental effects on rabbit embryo
      and foetal development, with two major peaks of losses: one before the
      implantation (at day 6) and the other during the second part of gestation (after
      day 14). However, foetal loss may occur during the implantation process and
      placenta development, as there was a reduction in development of foetus produced
      from vitrified-warmed embryos between day 10 and 14 of gestation. For these
      reasons, using a recent microarray study performed in frozen-thawed rabbit
      embryos as a point of reference, we analysed the effects of vitrification
      procedure on the expression of 10 candidate genes in 6-day-old blastocysts
      obtained after vitrification and transfer. We observed that the relative
      expressions of mRNA transcripts from SCGB1A1, EMP1, ANXA3 and EGFLAM genes were
      significantly altered. This could help explain why a large number (29%) of
      vitrified embryos were successfully implanted but subsequently failed to develop
      to term. Further studies in subsequent embryo-foetal developmental stages, such
      as initiation of placenta formation, together with more sensitive high-throughput
      tools, should help us understand the deficiencies that hinder foetal development
      and identify the repairing mechanism employed by embryos to overcome
      vitrification effects.

PMID- 24080488
TI  - Chimeric antigen receptors (CARs) from bench-to-bedside.
AB  - Chimeric antigen receptors (CARs) combine the antigen specificity of an antibody
      with the biologic properties of T lymphocytes. While the concept has been
      developed more than 20 years ago, only in recent years the clinical application
      of this approach has produced remarkable objective clinical responses. In this
      brief review, we outline some specific aspects that have led to antitumor
      responses in cancer patients. 

PMID- 24080490
TI  - Linking membrane physical properties and low temperature tolerance in arthropods.
AB  - Maintenance of membrane fluidity is of crucial importance in ectotherms
      experiencing thermal changes. This maintenance has in ectotherms most often been
      indicated using indirect measures of biochemical changes of phospholipid
      membranes, which is then assumed to modulate the physico-chemical properties of
      the membrane. Here, we measure bending rigidity characterizing the membrane
      flexibility of re-constituted membrane vesicles to provide a more direct link
      between membrane physical characteristics and low temperature tolerance. Bending
      rigidity of lipid bilayers was measured in vitro using Giant Unilamellar Vesicles
      formed from phospholipid extracts of the springtail, Folsomia candida. The
      bending rigidity of these membranes decreased when exposed to 0.4 vol% ethanol
      (0.23 mM/L). Springtails exposed to ethanol for 24h significantly increased their
      cold shock tolerance. Thus, by chemically inducing decreased membrane rigidity,
      we have shown a direct link between the physico-chemical properties of the
      membranes and the capacity to tolerate low temperature in a chill-susceptible
      arthropod.

PMID- 24080491
TI  - WITHDRAWN: Effects of various glycerol concentrations and thawing temperatures on
      CASA parameters and acrosomal integrity of frozen-thawed canine spermatozoa.
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- 24080492
TI  - Therapeutic strategies in male breast cancer: clinical implications of chromosome
      17 gene alterations and molecular subtypes.
AB  - Male breast cancer (MBC) is a rare disease. To date, therapy is mainly based on
      studies and clinical experiences with breast cancer in women. Only little is
      known about molecular typing of MBC, particularly with regard to potential
      biological predictors for adjuvant therapy. In female breast cancer tumors with
      chromosome 17 centromere (CEP17) duplication, HER2 and/or Topoisomerase II alpha
      (Topo II-alpha) gene alterations have been suggested to be associated with poor
      prognosis and increased sensitivity to anthracycline-containing regimens. In a
      well characterized cohort of 96 primary invasive MBC, we studied CEP17, HER2 and
      Topo II-alpha alterations by fluorescence in-situ hybridization (FISH), and
      expression of hormone receptors (HR), HER2 and Ki67 by immunohistochemistry to
      define molecular subtypes. Tumor characteristics and follow-up data were
      available and correlated with molecular findings. HER2 amplification and Topo II
      alpha amplification/deletion were exceptionally rare in MBC (6.3% and 3.1%,
      respectively). CEP17 polysomy were found in 9.4% of tumors. HER2, Topo II-alpha
      and CEP17 gene alterations were not correlated to patients outcome. 96.9% of our
      cases were HR positive. Triple negative tumors were found in only 3.1% of the
      cases. In nodal negative tumors luminal A subtypes were significantly associated
      with better overall survival. Our results provide evidence for a predominant male
      breast cancer phenotype, characterized by HR expression and a lack of HER2/Topo
      II-alpha alterations and CEP17 duplicates. Therefore, the impact of anthracycline
      sensitivity linked to HER2/Topo II-alpha alterations as found in female breast
      cancer has low clinical significance for this specific male breast cancer
      phenotype. 

PMID- 24080493
TI  - Level III axillary lymph nodes involvement in node positive breast cancer
      received neoadjuvant chemotherapy.
AB  - OBJECTIVE: To investigate the incidence, associated factors and prognosis of
      level III node involvement for breast cancer with positive axillary lymph nodes
      after neoadjuvant chemotherapy. METHODS: A consecutive series of 521 node
      positive T0-2 invasive breast cancer cases were included in this retrospective
      study. Axillary node metastases were proved by ultrasound guided needle biopsy
      (NB) if ultrasonographic abnormal node was detected or by sentinel node biopsy
      (SNB) if no abnormal node was detected. After 4 to 8 cycles of neoadjuvant
      chemotherapy (NCT), axillary lymph nodes dissection included level III lymph
      nodes were completed for each case. RESULTS: The pathologic complete response
      rate of axillary nodes was 31.1% (90/289) in NB positive subgroup. The incidence
      of residual positive level III lymph nodes were 9.0% (47/521). Multivariate
      analysis showed that node NB positivity (OR = 2.212, 95% CI: 1.022-4.787, P =
      0.044), clinical tumor size >2 cm before NCT (OR = 2.672, 95% CI: 1.170-6.098, P
      = 0.020), and primary tumor non-response to neoadjuvant chemotherapy (OR = 1.718,
      95% CI: 1.232-2.396, P = 0.001) were independent predictors of level III lymph
      nodes positivity. At median follow-up time of 30 months, the distant disease-free
      survival (DDFS) rate of level III node positive group was much lower than that of
      level III negative group (p = 0.011). CONCLUSIONS: About 9% of node positive T0-2
      breast cancer will have residual positive node in level III region after
      neoadjuvant chemotherapy. Node positivity proved by NB, large tumor size, and
      primary tumor non-response to neoadjuvant chemotherapy are independent predictors
      of level III lymph nodes positivity.

PMID- 24080494
TI  - Prevalence of sleep problems and relationship between sleep problems and school
      refusal behavior in school-aged children in children's and parents' ratings.
AB  - OBJECTIVE: This cross-section study investigated the prevalence of sleep
      disorders and the relationship between sleep problems (insomnias, parasomnias,
      and daytime sleepiness) and school refusal behavior in school-age children
      (fourth grade elementary school in Cologne, Germany). METHOD: A sample of 1,490
      children (age range: 8-11 years) and their parents each completed a sleep
      questionnaire and the School Refusal Assessment Scale. RESULTS: The results
      indicate that sleep problems in childhood are frequent. Furthermore, the results
      of the study clearly indicate that there is a relationship between sleep problems
      and school refusal behavior. Children suffering from insomnias (sleep onset
      problems, difficulties maintaining sleep), parasomnias (nightmares, night
      terrors), and daytime sleepiness showed without exception significantly higher
      scores in 3 out of 4 school refusal behavior maintaining conditions compared to
      children without sleep problems. These three conditions are all associated with
      anxiety disorders (anxiety or depressive disorder, as well as separation anxiety
      disorder). Only in the fourth condition, which is associated with oppositional
      defiant or conduct disorders, truancy, or no disorder at all, were there no
      significant differences between children with and children without sleep
      problems. CONCLUSIONS: For research and clinical practice, it is important to
      view sleep problems and school refusal behavior in relation to each other rather
      than as isolated phenomena.

PMID- 24080495
TI  - Human GEN1 and the SLX4-associated nucleases MUS81 and SLX1 are essential for the
      resolution of replication-induced Holliday junctions.
AB  - Holliday junctions (HJs), the DNA intermediates of homologous recombination, need
      to be faithfully processed in order to preserve genome integrity. In human cells,
      the BLM helicase complex promotes nonnucleolytic dissolution of double HJs. In
      vitro, HJs may be nucleolytically processed by MUS81-EME1, GEN1, and SLX4-SLX1.
      Here, we exploit human SLX4-null cells to examine the requirements for HJ
      resolution in vivo. Lack of BLM and SLX4 or GEN1 and SLX4 is synthetically lethal
      in the absence of exogenous DNA damage, and lethality is a consequence of
      dysfunctional mitosis proceeding in the presence of unprocessed HJs. Thus, GEN1
      activity cannot be substituted for the SLX4-associated nucleases, and one of the
      HJ resolvase activities, either of those associated with SLX4 or with GEN1, is
      required for cell viability, even in the presence of BLM. In vivo HJ resolution
      depends on both SLX4-associated MUS81-EME1 and SLX1, suggesting that they are
      acting in concert in the context of SLX4. 

PMID- 24080496
TI  - Atypical fibroxanthoma with pseudoangiomatous features: a histological and
      immunohistochemical mimic of cutaneous angiosarcoma.
AB  - Atypical fibroxanthoma and pleomorphic dermal sarcoma may be difficult to
      separate from cutaneous angiosarcoma. We aim to study the morphological spectrum
      of pseudoangiomatous features in these tumors and the value of staining for
      endothelial markers CD31, CD34, FLI1, and ERG. Eleven atypical fibroxanthomas and
      3 pleomorphic dermal sarcomas were identified. All tumors arose on sun-damaged
      skin of elderly men. Atypical fibroxanthomas were nodular and confined to the
      dermis, whereas pleomorphic dermal sarcoma invaded into underlying fascia. All
      tumors were composed of pleomorphic epithelioid and spindle cells showing blood
      filled spaces and intratumoral hemorrhage. Intracytoplasmic vacuoles (n = 4),
      hemosiderin deposition (n = 2), and keloidal stromal change (n = 1) were also
      noted. Immunohistochemically, CD31 was expressed in 43% of cases, FLI1 in 79% and
      smooth muscle actin in 50%. Staining for CD34, ERG, S100, HMB-45, desmin, p63 and
      cytokeratins was negative. Follow up (median, 43.1 months; range 1-100),
      available for 10 patients, showed no adverse outcome. Pseudoangiomatous features
      and aberrant expression of CD31 and FLI1 in atypical fibroxanthoma and
      pleomorphic dermal sarcoma may lead to an erroneous diagnosis of cutaneous
      angiosarcoma. Negativity for CD34 and ERG, in particular, is a reliable
      differentiating feature in this setting.

PMID- 24080497
TI  - Dual specificity phosphatase 1 expression inversely correlates with NF-kappaB
      activity and expression in prostate cancer and promotes apoptosis through a p38
      MAPK dependent mechanism.
AB  - Dual specificity phosphatase 1 (DUSP1) and the transcription factor NF-kappaB are
      implicated in prostate cancer since their expression levels are altered along
      this disease, although there are no evidences up to date demonstrating a
      crosstalk between them. In this report, we show for the first time that DUSP1
      over-expression in DU145 cells promotes apoptosis and decreases NF-kappaB
      activity by blocking p65/NF-kappaB nuclear translocation. Moreover, although
      DUSP1 impairs TNF-alpha-induced p38 MAPK and JNK activation, only the specific
      inhibition of p38 MAPK exerts the same effects than DUSP1 over-expression on both
      apoptosis and NF-kappaB activity. Consistently, DUSP1 promotes apoptosis and
      decreases NF-kappaB activity in cells in which p38 MAPK is induced by TNF-alpha
      treatment. These results demonstrate that p38 MAPK is specifically involved in
      DUSP1-mediated effects on both apoptosis and NF-kappaB activity. Interestingly,
      we show an inverse correlation between DUSP1 expression and activation of both
      p65/NF-kappaB and p38 MAPK in human prostate tissue specimens. Thus, most of
      apparently normal glands, benign prostatic hyperplasia and low-grade prostatic
      intraepithelial neoplasia samples show high DUSP1 expression and low levels of
      both nuclear p65/NF-kappaB and activated p38 MAPK. By contrast, DUSP1 expression
      levels are low or even absent in high-grade prostatic intraepithelial neoplasia
      and prostatic adenocarcinoma samples, whereas nuclear p65/NF-kappaB and activated
      p38 MAPK are highly expressed in the same samples. Overall, our results provide
      evidence for a role of DUSP1 in the apoptosis of prostate cancer cells, through a
      mechanism involving the inhibition of p38 MAPK and NF-kappaB. Furthermore, our
      findings suggest that the ratio between DUSP1 and p65/NF-kappaB expression
      levels, rather than the individual expression of both molecules, is a better
      marker for diagnostic purposes in prostate cancer. 

PMID- 24080498
TI  - Pharmacogenetic associations with plasma efavirenz concentrations and clinical
      correlates in a retrospective cohort of Ghanaian HIV-infected patients.
AB  - OBJECTIVES: Efavirenz is widely used in first-line antiretroviral therapy in sub
      Saharan Africa. However, exposure to efavirenz shows marked interindividual
      variability that is genetically mediated with potential for important
      pharmacodynamic consequences. The aims of this study were to assess the
      frequencies of CYP2B6, CYP2A6, UGT2B7 and CAR single nucleotide polymorphisms
      (SNPs) and their impact on plasma efavirenz concentration and
      clinical/immunological responses in Ghanaian patients. METHODS: Genomic DNA from
      800 HIV-infected patients was genotyped for selected SNPs by real-time PCR-based
      allelic discrimination. Mid-dose plasma efavirenz concentrations were measured
      for 521 patients using HPLC with UV detection. Clinical outcomes in 299 patients
      on efavirenz were retrospectively assessed. Univariate and multivariate linear
      regression were performed using best subset selection. Time-to-event outcomes
      were analysed using a Cox proportional hazards regression model. RESULTS: The
      variant allele frequencies for CYP2B6 516G>T (rs3745274), CYP2B6 983T>C
      (rs28399499), CYP2A6 -48T>G (CYP2B6*9B; rs28399433), UGT2B7 802C>T (UGT2B7*2;
      rs7439366), UGT2B7 735A>G (UGT2B7*1c; rs28365062) and CAR 540C>T (rs2307424) were
      48%, 4%, 3%, 23%, 15% and 7%, respectively. CYP2B6 516G>T, CYP2B6 983T>C and
      CYP2A6 -48T>G were associated with significantly elevated efavirenz
      concentrations. A trend towards association between plasma efavirenz
      concentration and CAR 540C>T was observed. CYP2B6 516G homozygosity was
      associated with immunological failure [adjusted hazards ratio compared with T
      homozygosity, 1.70 (1.04-2.76); P = 0.03]. CONCLUSIONS: CYP2B6 and CYP2A6 SNPs
      were associated with higher plasma efavirenz concentrations due to reduction in
      major and minor phase I routes of elimination, respectively. Further prospective
      studies are needed to validate the pharmacodynamic correlates of these
      polymorphisms in this population.

PMID- 24080499
TI  - Antibiotic prescription pattern among Indian oral healthcare providers: a cross
      sectional survey.
AB  - OBJECTIVES: Inappropriate prescribing of antibiotics by healthcare professionals
      is a worldwide concern. The purpose of this study was to determine the pattern of
      antibiotic prescription among oral healthcare providers in India. METHODS: A one
      page questionnaire was sent to 1600 oral healthcare practitioners registered
      under the Indian Dental Association by using multistage sampling; 552 (34.5%)
      responded to the survey. The data were analysed using the chi(2) test and
      multiple logistic regression analysis. RESULTS: Of 552 questionnaire respondents,
      405 (73.4%) chose amoxicillin in non-allergic patients, alone [279 (50.5%)] or
      associated with clavulanic acid [126 (22.8%)]. The average duration of antibiotic
      therapy was 4.26 +/- 1.26 days. The drug of first choice for patients with an
      allergy to penicillin was erythromycin [242 (43.8%) of respondents]. A majority
      prescribed antibiotics for irreversible pulpitis and acute apical periodontitis
      [395 (71.6%)] and necrotic pulp, acute apical periodontitis and no swelling [326
      (59.1%)]. Five hundred and ten (92.4%) of the oral healthcare providers
      overprescribed antibiotics. CONCLUSIONS: Oral healthcare providers in India are
      overprescribing, which could be a major contributor to the world problem of
      antimicrobial resistance. As there is overprescription of antibiotics by Indian
      oral healthcare providers, there is an urgent need to raise public and
      professional awareness regarding the risks of antibiotic use.

PMID- 24080500
TI  - In vitro activity of temocillin against multidrug-resistant clinical isolates of
      Escherichia coli, Klebsiella spp. and Enterobacter spp., and evaluation of high
      level temocillin resistance as a diagnostic marker for OXA-48 carbapenemase.

PMID- 24080501
TI  - Determinants of between-country differences in ambulatory antibiotic use and
      antibiotic resistance in Europe: a longitudinal observational study.
AB  - OBJECTIVES: To identify key determinants explaining country-year variations in
      antibiotic use and resistance. METHODS: Ambulatory antibiotic use data [in
      defined daily doses per 1000 inhabitants per day (DIDs)] for 19 European
      countries from 1999 to 2007 were collected, along with 181 variables describing
      countries in terms of their agriculture, culture, demography, disease burden,
      education, healthcare organization and socioeconomics. After assessing data
      availability, overlap and relevance, multiple imputation generalized estimating
      equations were applied with a stepwise selection procedure to select significant
      determinants of global antibiotic use (expressed in DIDs), relative use of
      subgroups (amoxicillin and co-amoxiclav) and resistance of Escherichia coli and
      Streptococcus pneumoniae. RESULTS: Relative humidity, healthcare expenditure
      proportional to gross domestic product, feelings of distrust, proportion of
      population aged >65 years and availability of treatment guidelines were
      associated with higher total antibiotic use expressed in DIDs. Restrictions on
      marketing activities towards prescribers, population density, number of
      antibiotics, educational attainment and degree of atheism were associated with a
      lower number of total DIDs used. Relative prescribing of amoxicillin and co
      amoxiclav was mainly determined by healthcare system choices [e.g. general
      practitioner (GP) registration and restricted marketing]. Specific antibiotic use
      was found to be a significant determinant of resistance for some but not all
      drug/organism combinations. Incentives to stimulate GP gatekeeping were
      associated with lower levels of resistance, and life expectancy at age 65+ and
      atheism were associated with more resistance. CONCLUSIONS: Myriad factors
      influence antibiotic use and resistance at the country level and an important
      part of these can be modified by policy choices.

PMID- 24080502
TI  - Identification of a marker for two lineages within the GC1 clone of Acinetobacter
      baumannii.

PMID- 24080504
TI  - Distributed BOLD and CBV-weighted resting-state networks in the mouse brain.
AB  - Laboratory mouse models represent a powerful tool to elucidate the biological
      foundations of disease, but translation to and from human studies rely upon valid
      cross-species measures. Resting-state functional connectivity (rsFC) represents a
      promising translational probe of brain function; however, no convincing
      demonstration of the presence of distributed, bilateral rsFC networks in the
      mouse brain has yet been reported. Here we used blood oxygen level dependent
      (BOLD) and cerebral blood volume (CBV) weighted fMRI to demonstrate the presence
      of robust and reproducible resting-state networks in the mouse brain. Independent
      component analysis (ICA) revealed inter-hemispheric homotopic rsFC networks
      encompassing several established neuro-anatomical systems of the mouse brain,
      including limbic, motor and parietal cortex, striatum, thalamus and hippocampus.
      BOLD and CBV contrast produced consistent networks, with the latter exhibiting a
      superior anatomical preservation of brain regions close to air-tissue interfaces
      (e.g. ventral hippocampus). Seed-based analysis confirmed the inter-hemispheric
      specificity of the correlations observed with ICA and highlighted the presence of
      distributed antero-posterior networks anatomically homologous to the human
      salience network (SN) and default-mode network (DMN). Consistent with rsFC
      investigations in humans, BOLD and CBV-weighted fMRI signals in the DMN-like
      network exhibited spontaneous anti-correlation with neighbouring fronto-parietal
      areas. These findings demonstrate the presence of robust distributed intrinsic
      functional connectivity networks in the mouse brain, and pave the way for the
      application of rsFC readouts in transgenic models to investigate the biological
      underpinnings of spontaneous BOLD fMRI fluctuations and their derangement in
      pathological states.

PMID- 24080503
TI  - Genomic identification of a novel co-trimoxazole resistance genotype and its
      prevalence amongst Streptococcus pneumoniae in Malawi.
AB  - OBJECTIVES: This study aimed to define the molecular basis of co-trimoxazole
      resistance in Malawian pneumococci under the dual selective pressure of
      widespread co-trimoxazole and sulfadoxine/pyrimethamine use. METHODS: We measured
      the trimethoprim and sulfamethoxazole MICs and analysed folA and folP nucleotide
      and translated amino acid sequences for 143 pneumococci isolated from carriage
      and invasive disease in Malawi (2002-08). RESULTS: Pneumococci were highly
      resistant to both trimethoprim and sulfamethoxazole (96%, 137/143).
      Sulfamethoxazole-resistant isolates showed a 3 or 6 bp insertion in the
      sulphonamide-binding site of folP. The trimethoprim-resistant isolates fell into
      three genotypic groups based on dihydrofolate reductase (encoded by folA)
      mutations: Ile-100-Leu (10%), the Ile-100-Leu substitution together with a
      residue 92 substitution (56%) and those with a novel uncharacterized resistance
      genotype (34%). The nucleotide sequence divergence and dN/dS of folA and folP
      remained stable from 2004 onwards. CONCLUSIONS: S. pneumoniae exhibit almost
      universal co-trimoxazole resistance in vitro and in silico that we believe is
      driven by extensive co-trimoxazole and sulfadoxine/pyrimethamine use. More than
      one-third of pneumococci employ a novel mechanism of co-trimoxazole resistance.
      Resistance has now reached a point of stabilizing evolution. The use of co
      trimoxazole to prevent pneumococcal infection in HIV/AIDS patients in sub-Saharan
      Africa should be re-evaluated.

PMID- 24080505
TI  - GABA transporter-1 inhibitor NO-711 alters the EEG power spectra and enhances non
      rapid eye movement sleep during the active phase in mice.
AB  - GABA transporter subtype 1 (GAT1) constructs high affinity reuptake sites for
      GABA in the CNS and regulates GABAergic transmission. Compounds that inhibit GAT1
      are targets often used for the treatment of epilepsy; however sedation has been
      reported as a side effect of these agents, indicating potential sedative and/or
      hypnotic uses for these compounds. In the current study, we observed the sleep
      behaviors of mice treated with NO-711, a selective GAT1 inhibitor, in order to
      elucidate the role of GAT1 in sleep-wake regulation during the active phase. The
      data revealed that NO-711 at a high dose of 10 mg/kg caused a marked enhancement
      of EEG activity in the frequency ranges of 3-25 Hz during wakefulness as well as
      rapid eye movement (REM) sleep. During the non-REM (NREM) sleep, NO-711 (10
      mg/kg) elevated EEG activity in the frequency ranges of 1.5-6.75 Hz. Similar
      changes were found in mice treated with a low dose of 3 mg/kg. NO-711
      administered i.p. at a dose of 1, 3 or 10 mg/kg significantly shortened the sleep
      latency of NREM sleep, increased the amount of NREM sleep and the number of NREM
      sleep episodes. NO-711 did not affect the sleep latency and the amount of REM
      sleep. NO-711 dose-dependently increased c-Fos expression in sleep-promoting
      nucleus of the ventrolateral preoptic area and median preoptic area. However, c
      Fos expression was decreased in the wake-promoting nuclei, tuberomammillary
      nucleus and lateral hypothalamus. These results indicate that NO-711 can increase
      NREM sleep in mice.

PMID- 24080506
TI  - Connexin 26 gene mutations in non-syndromic hearing loss among Kuwaiti patients.
AB  - OBJECTIVE: To study connexin 26 (Cx26) gene mutations among autosomal recessive
      non-syndromal hearing loss in Kuwaiti patients and evaluate their effect on
      phenotypes. SUBJECTS AND METHODS: This cross sectional study included 100
      patients aged between 6 months and 18 years, who were referred to the Sheikh
      Salem Al-Ali Centre for audiology and speech evaluation of autosomal recessive
      non-syndromic sensorineural hearing loss confirmed by clinico-genetic evaluation
      and a battery of diagnostic tests. Gene profiling and sequencing were performed
      to detect the presence and nature of Cx26 mutation. RESULTS: Of the 100 patients,
      mutation of Cx26 gene was detected in 15 patients (15%) of which 9 (60%) cases
      were heterozygous and 6 cases (40%) were homozygous. Eighty per cent of the 15
      Cx26 positive cases resulted from the 35delG mutation. Among the heterozygous
      cases, 6 (66.6%) were positive for 35delG. All 6 homozygous patients were
      positive for the 35delG mutation. A significant correlation was found between
      genetic findings (p = 0.013) and family history (p = 0.029), as well as the onset
      (p = 0.015), course (p = 0.033), degree and configuration of hearing loss (p =
      0.001). CONCLUSION: Among the selected Kuwaiti population sample, the Cx26 gene
      mutation was responsible for 15% of autosomal recessive non-syndromic
      sensorineural hearing loss. We recommend that screening for Cx26 gene mutation be
      considered in the screening strategy of patients with non-syndromic childhood
      hearing loss for counselling and management purposes. .

PMID- 24080507
TI  - Mortality and use of the auxiliary score in extensive toxic epidermal necrolysis
      patients admitted to an adult burns referral centre.
AB  - BACKGROUND: Toxic epidermal necrolysis (TEN) is a rare but fatal condition
      characterised by cutaneous exfoliation of the dermoepidermal layer and mucosal
      surfaces. Extensive TEN with epidermal detachment >30% of the total body surface
      area has been associated with a high mortality. OBJECTIVE: This study aims to
      evaluate factors associated with mortality in extensive TEN. In the absence of
      data to qualify scoring systems such as SCORTEN, this study also aims to evaluate
      the use of the auxiliary score as a tool for calculating expected mortality.
      METHODS: A retrospective chart review of all patients presenting to our burns
      service with extensive TEN was undertaken. Application and evaluation of the
      auxiliary score was also undertaken for this patient population. RESULTS: In
      extensive TEN, age and delay in admission to a burns centre were factors
      associated with mortality. Applying the auxiliary score to our patient
      population, there were no significant differences between expected mortality and
      observed mortality. CONCLUSION: Mortality was associated with age and delay in
      definitive treatment in extensive TEN. Whilst SCORTEN is the gold standard
      prognostic tool for patients with TEN, in the absence of SCORTEN values, the
      auxiliary score provides an alternative scoring system to evaluate expected
      mortality.

PMID- 24080508
TI  - Towards understanding ocular motility: III, IV and VI.
AB  - The study of the ocular-motor nerves must be exhaustive from their source (nuclei
      in the brainstem) down to the effector muscles (orbit). Visual disturbances have
      to be analysed by differentiating between a decrease in visual acuity and ocular
      motor disorders. Imaging tests are dominated by MRI, including fine slices and
      gadolinium injection. A study of the Circle of Willis vessels is often useful,
      and essential in the case of type III impairment. A further CT scan is essential
      for analysis of the foramina, base of the skull and orbital walls. Impairment of
      CN VI requires a CT scan of the apex of petrous. The study of the cavernous
      sinuses must be in-depth (T2 and T1 after gadolinium and elimination of fats) and
      always comparative. Impairment of CN III is often complex, difficult to identify
      precisely (complete or partial, with or without a pupil impairment, associated
      with other neurological signs) and requires a reasoned study based on anatomical,
      semiological and pathological knowledge. Other than tumour diseases, it is
      necessary to consider less well known malformative, ischemic and inflammatory
      aetiology. 

PMID- 24080509
TI  - The ubiquitin ligase Nedd4 regulates craniofacial development by promoting
      cranial neural crest cell survival and stem-cell like properties.
AB  - The integration of multiple morphogenic signalling pathways and transcription
      factor networks is essential to mediate neural crest (NC) cell induction,
      delamination, survival, stem-cell properties, fate choice and differentiation.
      Although the transcriptional control of NC development is well documented in
      mammals, the role of post-transcriptional modifications, and in particular
      ubiquitination, has not been explored. Here we report an essential role for the
      ubiquitin ligase Nedd4 in cranial NC cell development. Our analysis of Nedd4(-/-)
      embryos identified profound deficiency of cranial NC cells in the absence of
      structural defects in the neural tube. Nedd4 is expressed in migrating cranial NC
      cells and was found to positively regulate expression of the NC transcription
      factors Sox9, Sox10 and FoxD3. We found that in the absence of these factors, a
      subset of cranial NC cells undergo apoptosis. In accordance with a lack of
      cranial NC cells, Nedd4(-/-) embryos have deficiency of the trigeminal ganglia,
      NC derived bone and malformation of the craniofacial skeleton. Our analyses
      therefore uncover an essential role for Nedd4 in a subset of cranial NC cells and
      highlight E3 ubiquitin ligases as a likely point of convergence for multiple NC
      signalling pathways and transcription factor networks. 

PMID- 24080510
TI  - CK2alpha regulates the transcription of BRP in Drosophila.
AB  - Development and plasticity of synapses are brought about by a complex interplay
      between various signaling pathways. Typically, either changing the number of
      synapses or strengthening an existing synapse can lead to changes during synaptic
      plasticity. Altering the machinery that governs the exocytosis of synaptic
      vesicles, which primarily fuse at specialized structures known as active zones on
      the presynaptic terminal, brings about these changes. Although signaling pathways
      that regulate the synaptic plasticity from the postsynaptic compartments are well
      defined, the pathways that control these changes presynaptically are poorly
      described. In a genetic screen for synapse development in Drosophila, we found
      that mutations in CK2alpha lead to an increase in the levels of Bruchpilot (BRP),
      a scaffolding protein associated with the active zones. Using a combination of
      genetic and biochemical approaches, we found that the increase in BRP in CK2alpha
      mutants is largely due to an increase in the transcription of BRP. Interestingly,
      the transcripts of other active zone proteins that are important for function of
      active zones were also increased, while the transcripts from some other synaptic
      proteins were unchanged. Thus, our data suggest that CK2alpha might be important
      in regulating synaptic plasticity by modulating the transcription of BRP. Hence,
      we propose that CK2alpha is a novel regulator of the active zone protein, BRP, in
      Drosophila.

PMID- 24080511
TI  - The potential depigmenting activity of retinaldehyde.
AB  - BACKGROUND: Retinoids have been reported to exert depigmenting activity. Unlike
      most depigmenting agents that target tyrosinase, they are not phenolic agents and
      may act via different mechanisms. OBJECTIVES: We analysed the properties of
      retinaldehyde (RAL), a precursor of retinoic acid (RA), as a skin-lightening
      agent in various models. METHODS: The viability and the depigmenting properties
      of RAL were assessed in murine melanocytes, in human reconstructed epidermis, and
      in mice and guinea pigs. The melanin content and cytotoxicity were assessed in
      melanocytes; in 3-dimensional models, the melanin concentration and the number of
      active melanocytes were determined. RESULTS: RAL was taken up by melanocytes and
      mostly metabolised to retinol and retinyl esters, and to a lesser extent to RA.
      RAL decreased the melanin concentration of guinea pig ears and mouse tails by 54
      and 74%, respectively, and decreased the number of active melanocytes by 42 and
      77%, respectively. In reconstructed epidermis the melanin concentration was
      increased by 52%, whereas the number of active melanocytes decreased by 44%.
      CONCLUSION: RAL exerts a significant depigmenting activity with a mode of action
      that looks different from that of RA. Our data suggest a skin-lightening effect
      related to a melanolytic action (i.e. a decrease in melanin concentration,
      whatever the mechanism) rather than to melanocytotoxicity, besides other still
      unknown actions of RAL on melanocytes.

PMID- 24080515
TI  - Anterior cingulate cortex involvement in subclinical social anxiety.
AB  - We demonstrated differential activation in the anterior cingulate cortex (ACC)
      between subjects with high and low social anxiety in response to angry versus
      neutral faces. Activation in the ACC distinguished between facial expressions in
      the low, but not the high, anxious group. The ACC's role in threat processing is
      discussed. 

PMID- 24080513
TI  - Trabecular bone score is associated with volumetric bone density and
      microarchitecture as assessed by central QCT and HRpQCT in Chinese American and
      white women.
AB  - Although high-resolution peripheral quantitative computed tomography (HRpQCT) and
      central quantitative computed tomography (QCT) studies have shown bone structural
      differences between Chinese American (CH) and white (WH) women, these techniques
      are not readily available in the clinical setting. The trabecular bone score
      (TBS) estimates trabecular microarchitecture from dual-energy X-ray
      absorptiometry spine images. We assessed TBS in CH and WH women and investigated
      whether TBS is associated with QCT and HRpQCT indices. Areal bone mineral density
      (aBMD) by dual-energy X-ray absorptiometry, lumbar spine (LS) TBS, QCT of the LS
      and hip, and HRpQCT of the radius and tibia were performed in 71 pre- (37 WH and
      34 CH) and 44 postmenopausal (21 WH and 23 CH) women. TBS did not differ by race
      in either pre- or postmenopausal women. In the entire cohort, TBS positively
      correlated with LS trabecular volumetric bone mineral density (vBMD) (r = 0.664),
      femoral neck integral (r = 0.651), trabecular (r = 0.641) and cortical vBMD (r =
      0.346), and cortical thickness (C/I; r = 0.540) by QCT (p < 0.001 for all). TBS
      also correlated with integral (r = 0.643), trabecular (r = 0.574) and cortical
      vBMD (r = 0.491), and C/I (r = 0.541) at the total hip (p < 0.001 for all). The
      combination of TBS and LS aBMD predicted more of the variance in QCT measures
      than aBMD alone. TBS was associated with all HRpQCT indices (r = 0.20-0.52)
      except radial cortical thickness and tibial trabecular thickness. Significant
      associations between TBS and measures of HRpQCT and QCT in WH and CH pre- and
      postmenopausal women demonstrated here suggest that TBS may be a useful adjunct
      to aBMD for assessing bone quality.

PMID- 24080516
TI  - Abnormal white matter integrity and decision-making deficits in alcohol
      dependence.
AB  - To date, there is no study that explored the correlation of microstructural
      changes in the whole brain white matter (WM) and decision-making in alcohol
      dependent patients (ADP). In the present study, we applied Tract Based Spatial
      Statistics (TBSS) to study WM changes in ADP compared with healthy controls. We
      also tested whether there was any relationship between WM integrity and decision
      making in ADP. The study included 17 inpatient ADP who had been abstinent for at
      least 2 weeks before testing and scanning and 16 healthy control subjects. The
      Iowa Gambling Task (IGT) was used to measure decision-making. Results for the IGT
      showed a significant group (ADP vs. control) by block interaction. Follow-up
      univariate analyses of variance showed that the groups were significantly
      different in the last 20 trails. Four significant clusters were found in which
      fractional anisotropy was significantly lower in ADP than in control subjects,
      including the corpus callosum and parietal, occipital and frontal regions. We
      found significant correlations between impaired IGT performance in the last 20
      trials and WM integrity in these regions. Together, these results might help to
      explain observed decision making deficits in ADP. 

PMID- 24080519
TI  - Multiscale sampling model for motion integration.
AB  - Biologically plausible strategies for visual scene integration across spatial and
      temporal domains continues to be a challenging topic. The fundamental question we
      address is whether classical problems in motion integration, such as the aperture
      problem, can be solved in a model that samples the visual scene at multiple
      spatial and temporal scales in parallel. We hypothesize that fast interareal
      connections that allow feedback of information between cortical layers are the
      key processes that disambiguate motion direction. We developed a neural model
      showing how the aperture problem can be solved using different spatial sampling
      scales between LGN, V1 layer 4, V1 layer 6, and area MT. Our results suggest that
      multiscale sampling, rather than feedback explicitly, is the key process that
      gives rise to end-stopped cells in V1 and enables area MT to solve the aperture
      problem without the need for calculating intersecting constraints or crafting
      intricate patterns of spatiotemporal receptive fields. Furthermore, the model
      explains why end-stopped cells no longer emerge in the absence of V1 layer 6
      activity (Bolz & Gilbert, 1986), why V1 layer 4 cells are significantly more end
      stopped than V1 layer 6 cells (Pack, Livingstone, Duffy, & Born, 2003), and how
      it is possible to have a solution to the aperture problem in area MT with no
      solution in V1 in the presence of driving feedback. In summary, while much
      research in the field focuses on how a laminar architecture can give rise to
      complicated spatiotemporal receptive fields to solve problems in the motion
      domain, we show that one can reframe motion integration as an emergent property
      of multiscale sampling achieved concurrently within lamina and across multiple
      visual areas. 

PMID- 24080520
TI  - Bacterial etiology of acute otitis media in the era prior to universal
      pneumococcal vaccination in Taiwanese children.
AB  - BACKGROUND: Acute otitis media (AOM) is one of the most frequent bacterial
      infections in children. Streptococcus pneumoniae and nontypeable Haemophilus
      influenzae (NTHi) are the two major bacterial pathogens. Pneumococcal conjugate
      vaccine was introduced into Taiwan in 2005 and only some children were
      vaccinated. This retrospective study assessed the bacterial etiology of AOM and
      its antimicrobial susceptibility in the era prior to universal pneumococcal
      vaccination in Taiwan. METHODS: From December 2009 to November 2011, children
      presenting with AOM and having a middle ear effusion sample collected by
      tympanocentesis were enrolled. The study period was divided into two parts.
      Demographic data of patients and antibiotic susceptibility of the pathogens were
      collected and analyzed. Serotypes of S. pneumoniae were identified. RESULTS:
      Among the 151 episodes, 46% of samples found bacterial pathogens. S. pneumoniae
      and NTHi were the leading causes of AOM, detected in 55.7% and 22.9% of bacterial
      AOM episodes, respectively. The prevalent serotypes of S. pneumoniae were 19 A
      and 19 F. Significantly more pneumococcal and serotype 19 A AOM were found in the
      later study period (18.4% vs. 33.3%, p = 0.0036; 10.5% vs. 24.0%, p = 0.028).
      Among the 39 S. pneumoniae isolates, 11 strains (28.2%) were penicillin
      susceptible. Of the 16 NTHi, 10 (62.5%) were susceptible to
      amoxicillin/clavulanate and all were susceptible to cefotaxime. CONCLUSION: S.
      pneumoniae and NTHi were the leading causes of AOM in Taiwanese children in the
      study period. An increase in patient numbers and proportion of pneumococcal and
      serotype 19 A AOM occurred. Antimicrobial nonsusceptibility was common in the
      predominant pathogens.

PMID- 24080518
TI  - APOE associated hemispheric asymmetry of entorhinal cortical thickness in aging
      and Alzheimer's disease.
AB  - Across species structural and functional hemispheric asymmetry is a fundamental
      feature of the brain. Environmental and genetic factors determine this asymmetry
      during brain development and modulate its interaction with brain disorders. The
      e4 allele of the apolipoprotein E gene (APOE-4) is a risk factor for Alzheimer's
      disease, associated with regionally specific effects on brain morphology and
      function during the life span. Furthermore, entorhinal and hippocampal
      hemispheric asymmetry could be modified by pathology during Alzheimer's disease
      development. Using high-resolution magnetic resonance imaging and a cortical
      unfolding technique we investigated whether carrying the APOE-4 allele influences
      hemispheric asymmetry in the entorhinal cortex and the hippocampus among patients
      with Alzheimer's disease as well as in middle-aged and older cognitively healthy
      individuals. APOE-4 carriers showed a thinner entorhinal cortex in the left
      hemisphere when compared with the right hemisphere across all participants. Non
      carriers of the allele showed this asymmetry only in the patient group. Cortical
      thickness in the hippocampus did not vary between hemispheres among APOE-4 allele
      carriers and non-carriers. The APOE-4 allele modulates hemispheric asymmetry in
      entorhinal cortical thickness. Among Alzheimer's disease patients, this asymmetry
      might be less dependent on the APOE genotype and a more general marker of
      incipient disease pathology. 

PMID- 24080517
TI  - Neural activity to intense positive versus negative stimuli can help
      differentiate bipolar disorder from unipolar major depressive disorder in
      depressed adolescents: a pilot fMRI study.
AB  - Failure to distinguish bipolar depression (BDd) from the unipolar depression of
      major depressive disorder (UDd) in adolescents has significant clinical
      consequences. We aimed to identify differential patterns of functional neural
      activity in BDd versus UDd and employed two (fearful and happy) facial
      expression/ gender labeling functional magnetic resonance imaging (fMRI)
      experiments to study emotion processing in 10 BDd (8 females, mean age=15.1 +/-
      1.1) compared to age- and gender-matched 10 UDd and 10 healthy control (HC)
      adolescents who were age- and gender-matched to the BDd group. BDd adolescents,
      relative to UDd, showed significantly lower activity to both intense happy (e.g.,
      insula and temporal cortex) and intense fearful faces (e.g., frontal precentral
      cortex). Although the neural regions recruited in each group were not the same,
      both BDd and UDd adolescents, relative to HC, showed significantly lower neural
      activity to intense happy and mild happy faces, but elevated neural activity to
      mild fearful faces. Our results indicated that patterns of neural activity to
      intense positive and negative emotional stimuli can help differentiate BDd from
      UDd in adolescents.

PMID- 24080521
TI  - Acyl-CoA binding protein and epidermal barrier function.
AB  - The acyl-CoA binding protein (ACBP) is a 10kDa intracellular protein expressed in
      all eukaryotic species and mammalian tissues investigated. It binds acyl-CoA
      esters with high specificity and affinity and is thought to act as an
      intracellular transporter of acyl-CoA esters between different enzymatic systems;
      however, the precise function remains unknown. ACBP is expressed at relatively
      high levels in the epidermis, particularly in the suprabasal layers, which are
      highly active in lipid synthesis. Targeted disruption of the ACBP gene in mice
      leads to a pronounced skin and fur phenotype, which includes tousled and greasy
      fur, development of alopecia and scaling of the skin with age. Furthermore,
      epidermal barrier function is compromised causing a ~50% increase in
      transepidermal water loss relative to that of wild type mice. Lipidomic analyses
      indicate that this is due to significantly reduced levels of non-esterified very
      long chain fatty acids in the stratum corneum of ACBP(-/-) mice. Here we review
      the current knowledge of ACBP with special focus on the function of ACBP in the
      epidermal barrier. This article is part of a Special Issue entitled The Important
      Role of Lipids in the Epidermis and their Role in the Formation and Maintenance
      of the Cutaneous Barrier. Guest Editors: Kenneth R. Feingold and Peter Elias. 

PMID- 24080522
TI  - Synthesis of methoxy-X04 derivatives and their evaluation in Alzheimer's disease
      pathology.
AB  - BACKGROUND: Alzheimer's disease is characterized by two notorious protein
      aggregates in the brain: extracellular senile plaques mainly consisting of
      amyloid-beta peptides and tau-protein-derived intracellular paired helical
      filaments. The diagnosis of Alzheimer's disease is impaired by insufficient
      sensitivity and specificity of diagnostic methods to visualize these pathological
      hallmarks over all disease stages. OBJECTIVE: The established fluorescence marker
      methoxy-X04 stains plaques, tau tangles and amyloid-derived angiopathies with
      good specificity, yet it is limited by slow elimination in vivo. Since the need
      for new markers is high, we prepared methoxy-X04 derivatives and evaluated their
      potential as imaging agents in Alzheimer's disease pathology. METHODS AND
      RESULTS: In this study, we describe an improved synthesis for methoxy-X04 and its
      derivatives and their affinity determination for the respective protein targets
      by immunohistology and a displacement assay. CONCLUSION: This resulted in the
      identification of new derivatives of methoxy-X04 with improved binding affinity.

PMID- 24080523
TI  - The parallel sheath technique in severe iliac tortuosity: a simple and novel
      technique to improve catheter manoeuvrability.

PMID- 24080524
TI  - Liquid chromatography-tandem mass spectrometric assay for the cyclin-dependent
      kinase inhibitor AT7519 in mouse plasma.
AB  - A quantitative bioanalytical liquid chromatography-tandem mass spectrometric (LC
      MS/MS) assay for the cyclin-dependent kinase inhibitor AT7519 in mouse plasma was
      developed and validated. Plasma samples were pre-treated using protein
      precipitation with acetonitrile containing rucaparib as internal standard. After
      dilution with water, the extract was directly injected into the reversed-phase LC
      system. The eluate was transferred into the electrospray interface with positive
      ionization and the analyte was detected in the selected reaction monitoring mode
      of a triple quadrupole mass spectrometer. The assay was validated in a 5
      10,000ng/ml calibration range using double logarithmic calibration, 5ng/ml was
      the lower limit of quantification. Within day precisions (n=6) were 2.9-5.6%,
      between day (3 days; n=18) precisions 3.2-7.2%. Accuracies were between 95.9 and
      99.0% for the whole calibration range. The drug was stable under all relevant
      analytical conditions. Finally, the assay was successfully used to determine
      plasma pharmacokinetics after intraperitoneal administration of AT7519 in mice
      with neuroblastoma xenografts. 

PMID- 24080525
TI  - Metabonomic analysis of Allium macrostemon Bunge as a treatment for acute
      myocardial ischemia in rats.
AB  - Myocardial ischemia (MI) refers to a pathological state of the heart caused by
      reduced cardiac blood perfusion, which leads to a decreased oxygen supply in the
      heart and an abnormal myocardial energy metabolism. Acute myocardial ischemia
      (AMI) has posed a significant health risk for humans. Allium macrostemon Bunge
      (AMB), a popular traditional Chinese medicine, is used for MI treatment. The
      therapeutic effects of AMB were assessed and the detailed mechanisms of AMB for
      AMI treatment were investigated. We characterized the metabonomic variations in
      rats from the sham surgery, AMI, and AMB-pretreated AMI groups through a
      combination of nuclear magnetic resonance (NMR) spectroscopy and multivariate
      statistical analysis. Thirty-five metabolites including carbohydrates, a range of
      amino acids, and organic acids were detected. The (1)H NMR spectra of the rat
      serum were analyzed using the principal component analysis (PCA) and orthogonal
      projection to latent structures discriminate analysis (OPLS-DA). Results showed
      that AMI induced some physiological changes in rats and also led to metabolic
      disorders related to glycolysis promotion, amino acid metabolism disruption, and
      other metabolite metabolism perturbation. AMB pretreatment reduced the AMI injury
      and maintained metabolic balance, possibly by limiting the change in energy
      metabolism and regulating amino acid metabolism. These findings provide a
      comprehensive insight on the metabolic response of AMI rats to AMB pretreatment
      and are important for the use of AMB for AMI therapy. 

PMID- 24080526
TI  - Evaluation of supercritical fluid chromatography for testing of PEG adducts in
      pharmaceuticals.
AB  - Drug formulations containing polyethylene glycol may give rise to formation of
      reaction products between the aforementioned and the active pharmaceutical
      ingredient. Supercritical fluid chromatography has recently achieved new interest
      and improved instrumentation is now available. Here, supercritical fluid
      chromatography has been evaluated for its possible use for determination of
      reactions products formed between polyethylene glycol and active pharmaceutical
      ingredients. A mixture of polyethylene glycols with average molecular weights of
      400-6000Da was separated with supercritical fluid chromatography using silica
      columns and carbon dioxide modified with methanol as mobile phase. Satisfactory
      resolution (Rs=1.2) of the individual oligomers up to a molecular weight of
      1000Da was obtained using evaporative light scattering as detection technique.
      The active pharmaceutical ingredients, cetirizine or indomethacin were
      investigated in a reaction mixture containing polyethylene glycol 400 after
      incubation at 80 degrees C for 120h. Polyethylene glycol esters formed upon
      reaction with both active pharmaceutical ingredients were observed as polymeric
      patterns with ultraviolet detection and identified with mass spectrometry.
      Cetirizine was observed to be more reactive than indomethacin. The observed
      difference in reactivity is due to differences in polar and steric effects
      between cetirizine and indomethacin. Evaporative light scattering, ultraviolet
      absorbance and mass spectrometric detection were investigated and each detection
      technique has its own advantages and disadvantages, but in order to be able to
      detect selected impurities in the complex mixture of impurities formed, mass
      spectrometry is superior. 

PMID- 24080527
TI  - A spatio-temporal latent atlas for semi-supervised learning of fetal brain
      segmentations and morphological age estimation.
AB  - Prenatal neuroimaging requires reference models that reflect the normal spectrum
      of fetal brain development, and summarize observations from a representative
      sample of individuals. Collecting a sufficiently large data set of manually
      annotated data to construct a comprehensive in vivo atlas of rapidly developing
      structures is challenging but necessary for large population studies and clinical
      application. We propose a method for the semi-supervised learning of a spatio
      temporal latent atlas of fetal brain development, and corresponding segmentations
      of emerging cerebral structures, such as the ventricles or cortex. The atlas is
      based on the annotation of a few examples, and a large number of imaging data
      without annotation. It models the morphological and developmental variability
      across the population. Furthermore, it serves as basis for the estimation of a
      structures' morphological age, and its deviation from the nominal gestational age
      during the assessment of pathologies. Experimental results covering the
      gestational period of 20-30 gestational weeks demonstrate segmentation accuracy
      achievable with minimal annotation, and precision of morphological age
      estimation. Age estimation results on fetuses suffering from lissencephaly
      demonstrate that they detect significant differences in the age offset compared
      to a control group. 

PMID- 24080528
TI  - Organ-focused mutual information for nonrigid multimodal registration of liver CT
      and Gd-EOB-DTPA-enhanced MRI.
AB  - Accurate detection of liver lesions is of great importance in hepatic surgery
      planning. Recent studies have shown that the detection rate of liver lesions is
      significantly higher in gadoxetic acid-enhanced magnetic resonance imaging (Gd
      EOB-DTPA-enhanced MRI) than in contrast-enhanced portal-phase computed tomography
      (CT); however, the latter remains essential because of its high specificity, good
      performance in estimating liver volumes and better vessel visibility. To
      characterize liver lesions using both the above image modalities, we propose a
      multimodal nonrigid registration framework using organ-focused mutual information
      (OF-MI). This proposal tries to improve mutual information (MI) based
      registration by adding spatial information, benefiting from the availability of
      expert liver segmentation in clinical protocols. The incorporation of an
      additional information channel containing liver segmentation information was
      studied. A dataset of real clinical images and simulated images was used in the
      validation process. A Gd-EOB-DTPA-enhanced MRI simulation framework is presented.
      To evaluate results, warping index errors were calculated for the simulated data,
      and landmark-based and surface-based errors were calculated for the real data. An
      improvement of the registration accuracy for OF-MI as compared with MI was found
      for both simulated and real datasets. Statistical significance of the difference
      was tested and confirmed in the simulated dataset (p<0.01). 

PMID- 24080529
TI  - Chromosome painting reveals multiple rearrangements between Gymnotus capanema and
      Gymnotus carapo (Gymnotidae, Gymnotiformes).
AB  - The genus Gymnotus (Gymnotiformes) is a group of fishes with karyotypic
      plasticity, demonstrated by cytogenetic studies using whole chromosome probes of
      G. carapo (GCA, 2n = 42) that were obtained by flow-sorting from fibroblast
      cultures. In the present work we undertook comparative mapping of the karyotype
      of G. capanema (GCP, 2n = 34) with GCA, 2n = 42 painting probes. The results
      demonstrate that the karyotype of G. capanema is extensively rearranged when
      compared to G. carapo. From the 12 chromosome pairs of G. carapo that can be
      individually differentiated (GCA1-3, 6, 7, 9, 14, 16 and 18-21), only 4 pairs
      (GCA6, 7, 19, and 20) maintained conserved synteny in G. capanema. From these 4,
      GCA6 and GCA20 correspond to individual chromosomes (GCP8 and GCP15), while the
      other 2 share homology with parts of GCP1 and GCP2, respectively. The remaining
      GCP chromosomes showed more complex hybridization patterns with homologies to
      other GCA pairs. These results demonstrate that the level of reorganization in
      the genome of G. capanema is much greater than in GCA, 2n = 42 and in karyomorph
      GCA, 2n = 40 which was previously analyzed by chromosome painting.

PMID- 24080530
TI  - A tissue-dependent hypothesis of dental caries.
AB  - Current understanding of dental caries considers this disease a demineralization
      of the tooth tissues due to the acid produced by sugar-fermenting microorganisms.
      Thus, caries is considered a diet- and pH-dependent process. We present here the
      first metagenomic analysis of the bacterial communities present at different
      stages of caries development, with the aim of determining whether the bacterial
      composition and biochemical profile are specific to the tissue affected. The data
      show that microbial composition at the initial, enamel-affecting stage of caries
      is significantly different from that found at subsequent stages, as well as from
      dental plaque of sound tooth surfaces. Although the relative proportion of
      Streptococcus mutans increased from 0.12% in dental plaque to 0.72% in enamel
      caries, Streptococcus mitis and Streptococcus sanguinis were the dominant
      streptococci in these lesions. The functional profile of caries-associated
      bacterial communities indicates that genes involved in acid stress tolerance and
      dietary sugar fermentation are overrepresented only at the initial stage (enamel
      caries), whereas other genes coding for osmotic stress tolerance as well as
      collagenases and other proteases enabling dentin degradation are significantly
      overrepresented in dentin cavities. The results support a scenario in which pH
      and diet are determinants of the disease during the degradation of enamel, but in
      dentin caries lesions not only acidogenic but also proteolytic bacteria are
      involved. We propose that caries disease is a process of varying etiology, in
      which acid-producing bacteria are the vehicle to penetrate enamel and allow
      dentin degrading microorganisms to expand the cavity.

PMID- 24080531
TI  - The G protein-coupled estrogen receptor 1 (GPER1/GPR30) agonist G-1 regulates
      vascular smooth muscle cell Ca2+ handling.
AB  - The G protein-coupled estrogen receptor GPER1/GPR30 is implicated in blood
      pressure regulation but the mechanisms are not identified. Here, we hypothesize
      that GPER1 controls blood pressure by regulating vascular smooth muscle cell
      Ca(2+) handling. Treatment with the GPER1 agonist G-1 (in the uM concentration
      range) acutely reduced spontaneous and synchronous Ca(2+) spike activity in A7r5
      vascular smooth muscle cells expressing mRNA for GPER1. Furthermore, G-1 (1 uM)
      attenuated the thromboxane A2 analogue U46619-stimulated Ca(2+) spike activity
      but had no effect on the U46619-induced increase in the basal level of Ca(2+).
      The voltage-sensitive L-type Ca(2+) channel blocker nifedipine (100 nM) reduced
      Ca(2+) spike activity similar to G-1. Pharmacological, but not physiological,
      concentrations of the estrogen 17beta-estradiol reduced Ca(2+) spike activity.
      The GPER1 antagonist G-15 blocked G-1-induced downregulation of Ca(2+) spike
      activity, supporting a GPER1-dependent mechanism. G-1 (1 uM) and nifedipine (100
      nM) attenuated the 30-mM KCl-evoked rise in intracellular Ca(2+) concentration,
      suggesting that G-1 blocks inflow of Ca(2+) via voltage-sensitive Ca(2+)
      channels. In conclusion, we demonstrate that the GPER1 agonist G-1 regulates
      vascular smooth muscle cell Ca(2+) handling by lowering Ca(2+) spike activity,
      suggesting a role for this mechanism in GPER1-mediated control of blood pressure.
      (c) 2013 S. Karger AG, Basel. 

PMID- 24080532
TI  - The spontaneous decay and persistence of mental contamination: an experimental
      analysis.
AB  - BACKGROUND AND OBJECTIVES: It has recently been identified that feelings of
      contamination can arise in the absence of physical contact with a stimulus. This
      concept, known as 'mental contamination' has particular relevance to Obsessive
      Compulsive Disorder in which compulsive cleaning is a common symptom
      presentation. Experimental studies have begun to examine the psychopathology of
      mental contamination. The aims of the two experiments reported here were to
      explore the evocation and spontaneous decay of mental contamination. METHODS: In
      Experiment 1, a variant of the autobiographical memory task was used in which 40
      non-clinical participants were asked to recall autobiographical memories
      associated with betrayal, harm, humiliation and violation of moral standards. In
      Experiment 2, 60 participants with moderate levels of mental contamination were
      asked to complete five short tasks designed to induce mental contamination,
      including recalling unwanted memories and images. RESULTS: In both experiments,
      participants reported significant increases in mental contamination, anxiety,
      urges to wash and actual washing behaviour. In experiment 1, the effect of the
      induction decayed spontaneously. Experiment 2 found that re-evoking contamination
      and repeated washing led to the persistence of mental contamination. LIMITATIONS:
      The studies were conducted on non-clinical samples. CONCLUSIONS: These findings
      demonstrated that repeated triggers may be causally connected to the maintenance
      of mental contamination fears in non-clinical samples.

PMID- 24080533
TI  - Protective effect of bilberry extract as a pretreatment on induced oral mucositis
      in hamsters.
AB  - OBJECTIVE: This study evaluated the effect of standardized bilberry extract
      containing anthocyanosides on chemotherapy-induced oral mucositis in hamsters.
      STUDY DESIGN: Twenty-four hamsters were randomly chosen and assigned to groups.
      Groups A and B were pretreated with deionized water, whereas group C was
      pretreated with bilberry extract daily for 7 days. Groups B and C underwent
      chemotherapy by intraperitoneal injections of 5-fluorouracil (days 4, 9, and 14);
      group A received normal saline. Potentiation of oral mucositis was achieved by
      scratching both cheek pouches of all animals with needles (days 5, 6, and 14).
      The pouches were histopathologically examined on day 17 after visual examination
      and blood sampling by cardiac puncture. RESULTS: The bilberry extract group
      showed significantly lower oral mucositis clinical and histopathologic scores (P
      < .05) and less percentile of mean daily weight reductions compared with animals
      receiving vehicle. CONCLUSIONS: Frequent administration of bilberry extract had a
      protective effect on oral mucosal damage induced by 5-fluorouracil in an animal
      model.

PMID- 24080534
TI  - Fodipir and its dephosphorylated derivative dipyridoxyl ethyldiamine are involved
      in mangafodipir-mediated cytoprotection against 7beta-hydroxycholesterol-induced
      cell death.
AB  - OBJECTIVE: Mangafodipir exerts pharmacological effects, including vascular
      relaxation and protection against oxidative stress and cell death induced by
      oxysterols. Additionally, mangafodipir has been proposed for cardiovascular
      imaging. The primary metabolites of mangafodipir, manganese dipyridoxyl
      ethyldiamine (MnPLED) and its constituent dipyridoxyl diphosphate (Dp-dp) also
      known as fodipir, are pharmacologically active. However, whether they affect
      oxysterol-induced cytotoxicity is currently unknown. In this study, we examine
      whether the mangafodipir metabolite affects 7beta-hydroxycholesterol (7beta-OH)
      induced cell death and identify the underlying mechanisms. METHODS: U937 cells
      were pretreated or not with mangafodipir substrate (Ms; 200 um), MnPLED (100
      umol/l) or Dp-dp (100 umol/l) for 8 h and then exposed to 7beta-OH (28 umol/l)
      for 18 h. RESULTS: Our results revealed that pretreatment with MnPLED or Dp-dp
      protected against 7beta-OH-induced cellular reactive oxygen species (ROS)
      production, apoptosis, and lysosomal membrane permeabilization (LMP). MnPLED and
      Dp-dp, in par with Ms, confer protection against 7beta-OH-induced cytotoxicity by
      reducing cellular ROS and stabilization of the lysosomal membrane. CONCLUSION:
      These results suggest that fodipir is the pharmacologically active part in the
      structure of mangafodipir, which prevents 7beta-OH-induced cell death by
      attenuating cellular ROS and by preventing LMP. In addition, MnPLED, which is the
      dephosphorylated product of fodipir, exerts a similar protective effect against
      7beta-OH-induced cytotoxicity. This result indicates that dephosphorylation of
      fodipir does not affect its pharmacological actions. Altogether our result
      confirms the cytoprotective effect of mangafodipir and justifies its potential
      use as a cytoprotective adjuvant.

PMID- 24080535
TI  - Improving medication safety through the use of metrics.
AB  - PURPOSE: Describe medication safety metrics used at University HealthSystem
      Consortium (UHC) institutions and recommend a meaningful way to report and
      communicate medication safety information across an organization. METHODS: A
      cross-sectional study was conducted using an electronically distributed, open
      ended survey instrument. RESULTS: Twenty percent of the UHC institutions
      responded to our survey. Seventy-seven percent of those institutions responding
      to our survey reported their organization has defined metrics to measure
      medication safety; an additional 21% of the institutions were still in the
      process of defining metrics. Of metrics that were reported, 33% were true
      medication safety metrics. Results are distributed to a wide variety of
      institutional venues. CONCLUSION: Institutions should take several actions
      related to medication safety including defining local metrics; building metrics
      addressing preventable adverse drug events, medication errors, and technology;
      and reporting results to a variety of venues in order to design specific
      interventions to improve local medication use.

PMID- 24080536
TI  - Safety of varenicline in patients with cardiovascular disease.
AB  - Smoking cessation lowers the risk of death substantially in patients with
      cardiovascular disease. Although varenicline is an effective medication for
      smoking cessation, its safety in this population has been questioned and
      evaluated in several studies. In 2 randomized controlled trials of patients with
      cardiovascular disease, the rates of serious cardiovascular events were up to 2%
      higher in patients receiving varenicline than placebo, though the differences
      were not statistically significant. In the first meta-analysis of mostly trials
      involving patients with a history of cardiovascular disease, varenicline was
      found to significantly increase the risk of cardiovascular events by 72%;
      however, a second meta-analysis did not find a significant increased risk. In an
      observational study, varenicline was not associated with an increased risk of
      events when compared to bupropion in a subgroup analysis of patients with a
      history of cardiovascular disease. Because the evidence on the safety of
      varenicline in this population is limited and conflicting, additional data are
      needed to formulate stronger conclusions. In the meantime, health care
      professionals should consider individual smoking patterns, concomitant medical
      conditions, and cost when recommending smoking cessation pharmacotherapy for
      patients with cardiovascular disease. 

PMID- 24080537
TI  - Sociodemographic characterization of ECT utilization in Hawaii.
AB  - OBJECTIVES: Minimal research has been done on sociodemographic differences in
      utilization of electroconvulsive therapy (ECT) for refractory depression,
      especially among Asian Americans and Pacific Islanders. METHODS: This study
      examined sociodemographic and diagnostic variables using retrospective data from
      Hawaii, an island state with predominantly Asian Americans and Pacific Islanders.
      Retrospective data were obtained from an inpatient and outpatient database of ECT
      patients from 2008 to 2010 at a tertiary care community hospital on O'ahu,
      Hawaii. RESULTS: There was a significant increase in overall ECT utilization from
      2008 to 2009, with utilization remaining stable from 2009 to 2010. European
      Americans (41%) and Japanese Americans (29%) have relatively higher rates of
      receiving ECT, and Filipino Americans and Native Hawaiians have relatively lower
      rates in comparison with their population demographics. Japanese Americans
      received significantly more ECT procedures than European Americans. CONCLUSIONS:
      Electroconvulsive therapy is underutilized by certain sociodemographic groups
      that may benefit most from the treatment. There are significant differences in
      ECT usage based on ethnicity. Such differences may be related to help-seeking
      behavior, economic differences, and/or attitudes regarding mental illness.
      Further research is needed to elucidate the reasons for differences in
      utilization.

PMID- 24080538
TI  - Practical considerations in the use of ultrabrief ECT in clinical practice.
AB  - OBJECTIVE: Electroconvulsive therapy (ECT) is the most effective treatment for
      major depression. Brief pulse width (BPW; pulse width, 1.0 m/s) ECT is often
      associated with cognitive impairment. Ultrabrief (UB; pulse width, 0.3 m/s) ECT
      is better tolerated and causes less cognitive impairment so has been introduced
      as an alternative. Previous research has shown that more treatments are needed
      with UB ECT; however, there has not been any previous research into the impact of
      prescribing UB ECT on length of stay. METHODS: This study reports naturalistic
      data collected from 258 inpatients in a private psychiatric hospital for 2 years
      since the introduction of UB ECT. Clinician and self-rated scales of depression
      severity and hospital service data were used to evaluate the number of ECT
      treatments, length of stay, and efficacy. RESULTS: Patients prescribed UB ECT
      had, on average, 10.9 treatments compared to 8.8 for BPW ECT. They also spent
      more time in hospital; 30.3 days from the first ECT treatment to discharge
      compared to 24.7 days for patients prescribed BPW ECT. Excluding patients who
      switched treatments, 54% of patients prescribed UB ECT responded compared to
      66.7% of patients prescribed BPW ECT. More patients (n = 42) switched from UB to
      BPW than from BPW to UB (n = 3). In the 4 years since the introduction of UB ECT,
      the number of patients prescribed ECT has increased, and the mean number of
      treatments per patient (for all patients receiving ECT) has increased from 7.7 to
      11.6. CONCLUSIONS: Ultrabrief ECT has significant advantages, reflected in the
      increased use of ECT since UB ECT became available. However, the greater number
      of treatments and the increased length of stay have important implications for
      service delivery, costs, and bed accessibility.

PMID- 24080540
TI  - Electroconvulsive therapy in a patient with pulmonary aneurysm.
AB  - Pulmonary artery aneurysm is a rare abnormality in the cardiovascular system.
      Electroconvulsive therapy triggers a release of catecholamines, causing a marked
      and usually transient tachycardia and hypertension, which could increase the risk
      of aneurysmal rupture. We report a case of a 56-year-old woman with severe
      depression and an incidental finding of a large left pulmonary artery aneurysm
      who received 16 treatments of electroconvulsive therapy without adverse effect.

PMID- 24080539
TI  - Efficacy of right unilateral ultrabrief pulse width ECT: a preliminary report.
AB  - BACKGROUND AND OBJECTIVES: Ultrabrief (right unilateral) electroconvulsive
      therapy (UB-RU ECT) is a newer form of ECT, which uses a shorter pulse width than
      the standard ECT (0.3 vs 1.0 millisecond, respectively). As a result, the use of
      UB ECT may provide a means of further decreasing ECT-related cognitive adverse
      effects. In 2011, the University of Texas Southwestern Department of ECT in
      Austin adopted a UB ECT protocol. The purpose of this study was to perform a
      preliminary evaluation of the effectiveness and efficiency of UB-RU ECT. This
      study also examined whether sex, age, or diagnosis affected response rates.
      METHODS: This retrospective chart review identified 62 patients treated with the
      UB ECT protocol. An analysis of ECT response rates and demographic
      characteristics was conducted based on the data from clinical evaluations and
      Patient Health Questionnaire 9. RESULTS: Sixty-eight percent of patients in the
      study responded to ECT; 55% responded to UB pulse width RU ECT with another 13%
      responding when switched to standard pulse width bilateral ECT. The mean number
      of treatments in an index ECT series was 12.5. There was no statistically
      significant difference in response rates between bipolar and unipolar depressed
      patients. Men required progression to bilateral treatment more than women.
      CONCLUSIONS: This UB ECT protocol demonstrated a similar response rate when
      compared to standard ECT protocols; however, an increase in the number of
      treatments was required. Ultrabrief protocols are a viable option for both
      bipolar and unipolar depression. In men, UB ECT protocols may be less
      advantageous due to a need to overcome a potentially higher seizure threshold in
      men; however, additional research is needed to confirm this finding.

PMID- 24080543
TI  - Assessment of cognitive performance using CNS vital signs after electroconvulsive
      treatment of schizophrenia.
AB  - Little is known how electroconvulsive therapy (ECT) affects cognitive functions
      in subjects with schizophrenia. Assessment of cognitive functions in subjects
      with schizophrenia treated with ECT was performed using CNS Vital Signs
      computerized battery of tests. Thirteen patients treated with ECT plus
      antipsychotics were assessed before and after 12 to 15 bilateral ECT sessions. We
      did not find any important changes between pre-ECT and post-ECT cognitive
      performance. We also found that CNS Vital Signs is a useful computerized battery
      test for assessing cognitive functions of subjects treated with ECT. 

PMID- 24080544
TI  - Neural basis of tDCS effects on auditory verbal hallucinations in schizophrenia:
      a case report evidence for cortical neuroplasticity modulation.
AB  - Transcranial direct current stimulation (tDCS) has been reported to ameliorate
      auditory hallucinations that are nonresponsive/minimally responsive to
      antipsychotic treatment in schizophrenia. The neurobiological basis of the tDCS
      effects in ameliorating auditory hallucinations is yet to be explored. In this
      case report, for the first time, using the novel method for noninvasive
      assessment of cortical plasticity, we demonstrate potential neuroplasticity
      effect of tDCS in improving treatment-resistant auditory hallucinations in a
      schizophrenic patient. 

PMID- 24080546
TI  - Is inadequate tissue perfusion a relevant issue during neurosurgery?

PMID- 24080547
TI  - Dyspnoeic neutropenia: an entity deserving specific efforts.

PMID- 24080545
TI  - Type IV pilus of Pseudomonas aeruginosa confers resistance to antimicrobial
      activities of the pulmonary surfactant protein-A.
AB  - Pseudomonas aeruginosa(PA) is a Gram-negative bacterial pathogen commonly
      associated with chronic lung infections. Previously, we have identified several
      PA virulence factors that are important for resistance to the surfactant protein
      A (SP-A), a pulmonary innate immunity protein that mediates bacterial
      opsonization and membrane permeabilization. In this study, we demonstrate that
      the type IV pilus (Tfp) is important in the resistance of PA to the antibacterial
      effects of SP-A. The Tfp-deficient mutant DeltapilA is severely attenuated in an
      acute pneumonia model of infection in the lungs of wild-type mice, but is
      virulent in the lungs of SP-A(-/-) mice. The DeltapilA bacteria are more
      susceptible to SP-A-mediated aggregation and opsonization. In addition, the
      integrity of the outer membranes of DeltapilA bacteria is compromised, rendering
      them more susceptible to SP-A-mediated membrane permeabilization. By comparing
      Tfp extension and retraction mutants, we demonstrate that the increased
      susceptibility of DeltapilA to SP-A-mediated opsonization requires the total
      absence of Tfp from PA cells. Finally, we provide evidence of increased
      expression of nonpilus adhesin OprH that may serve as an SP-A ligand, resulting
      in increased phagocytosis and preferential pulmonary clearance of DeltapilA.

PMID- 24080548
TI  - The role of reflectance confocal microscopy as an aid in the diagnosis of
      collision tumors.
AB  - BACKGROUND: The term 'collision tumor' refers to the association of 2 or more
      different neoplasms within the same lesion. The association of a benign neoplasm
      with a malignant neoplasm is of particular significance and warrants diagnostic
      accuracy. OBJECTIVE: The purpose of our study was to see if reflectance confocal
      microscopy (RCM) was a valuable tool when dealing with collision tumors. METHODS:
      We retrospectively evaluated 24 histologically confirmed cases of collision
      tumors, which were initially assessed using dermoscopy and RCM. RESULTS: The
      malignancy most commonly detected in association with collision tumors was basal
      cell carcinoma (BCC) (n = 13), followed by melanoma (n = 5, of which 2 collided
      with BCC) and squamous cell carcinoma in situ (n = 4). Seborrheic keratoses were
      the most common benign neoplasms found in association with collision tumors (n =
      18), followed by nevi (n = 7). Dermoscopy revealed the malignant component in 14
      out of 20 lesions compared to RCM, which revealed a malignant component in 19 out
      of 20 neoplasms. There was excellent concordance between RCM and histopathology
      with regard to the identification of a malignant component within a tumor (kappa
      value >0.9). CONCLUSION: The dermatoscope and the reflectance confocal
      microscope, when used in conjunction, are valuable tools aiding in the diagnosis
      of collision tumors.

PMID- 24080549
TI  - Restoration of renal responsiveness to atrial natriuretic peptide in experimental
      nephrotic syndrome by albumin infusion.
AB  - BACKGROUND: The natriuretic/diuretic response to atrial natriuretic peptide
      (ANP), an important regulator of water and Na(+) balance, is markedly attenuated
      in nephrotic syndrome (NS). It has been suggested that the diminished renal
      responsiveness to ANP may contribute to the pathogenesis of salt retention and
      edema formation in NS. However, the mechanisms underlying the renal
      hyporesponsiveness to ANP remain largely unknown. METHODS: The acute effects of
      exogenous infusion of ANP (5 ug/kg + 10 ug/kg/h) were studied by clearance
      methodology in control rats, hypoalbuminemic rats with Adriamycin (ADR)-induced
      NS and in ADR-treated rats infused with hyperoncotic albumin sufficient to
      restore plasma albumin to normal levels. RESULTS: Administration of ANP to
      control rats resulted in a significant increase in urinary flow rate, absolute
      rate of sodium excretion (+456%) and glomerular filtration rate (GFR). Mean
      arterial blood pressure decreased following infusion of the peptide. In the
      nephrotic rats, baseline GFR and Na(+) excretion were significantly lower than in
      the control animals, and the renal effects of ANP were markedly blunt compared to
      the control animals. In contrast, the hypotensive effect of ANP in the ADR
      treated rats was largely preserved. Infusion of hyperoncotic albumin prior to ANP
      administration reversed the decrease in baseline GFR and Na(+) excretion and
      completely restored the renal effects of ANP in the nephrotic rats. CONCLUSION:
      These findings indicate that renal hyporesponsiveness to ANP in rats with ADR
      induced NS is a reversible phenomenon that appears to be of functional origin
      rather than reflecting permanent cellular damage.

PMID- 24080550
TI  - Suppression of TRIF-dependent signaling pathway of toll-like receptors by (E)-1
      (2-(2-nitrovinyl)phenyl)pyrrolidine.
AB  - Toll-like receptors (TLRs) play an important role in the recognition of microbial
      pathogens and induce innate immune responses. The recognition of microbial
      components by TLRs triggers the activation of myeloid differential factor 88
      (MyD88)- and toll-interleukin-1 receptor domain-containing adapter inducing
      interferon-beta (TRIF)-dependent downstream signaling pathways. Previously, we
      synthesized (E)-1-(2-(2-nitrovinyl)phenyl)pyrrolidine (NVPP), which contains a
      nitrovinyl-phenyl and pyrrolidine. To evaluate the therapeutic potential of NVPP,
      its effect on signal transduction via the TRIF-dependent pathway of TLRs induced
      by lipopolysaccharide (LPS) or polyinosinic-polycytidylic acid (poly[I:C]) was
      examined. NVPP inhibited LPS or poly[I:C]-induced activation of nuclear factor
      kappaB (NF-kappaB) and interferon regulatory factor 3 (IRF3), and the
      phosphorylation of IRF3, as well as inhibiting the activation of interferon
      inducible genes such as interferon inducible protein-10 (IP-10). These results
      suggest that NVPP can modulate TRIF-dependent signaling pathways of TLRs,
      potentially resulting in effective therapeutics for chronic inflammatory
      diseases.

PMID- 24080551
TI  - The health effects of fetal microchimerism can be modeled in companion dogs.
AB  - Fetal microchimerism (FMC) has been described to have a range of effects on
      health and disease. Y-chromosomal DNA has been detected in Golden Retrievers
      suggesting persistent FMC. In that report, nine dogs had evidence of
      microchimerism without prior pregnancy. To further understand this finding, a dam
      with prior male live births giving birth to her fourth litter of puppies, all
      females, was evaluated for FMC along with two of her daughters. All three female
      dogs had evidence of Y-chromosomal DNA in their blood. This suggests that male
      cells carried by the dam from previous pregnancy trafficked to her daughters to
      establish microchimerism in younger siblings. Companion dogs share many of the
      same cancers as humans, have out-bred genetics, and share the human environment,
      making them optimal models of human disease. Understanding the impact of FMC on
      health and disease of dogs could elucidate mechanisms useful for clinical
      interventions in humans. 

PMID- 24080552
TI  - Emotional functioning, barriers, and medication adherence in pediatric transplant
      recipients.
AB  - OBJECTIVE: This study assessed relationships among internalizing symptoms,
      barriers to medication adherence, and medication adherence in adolescents with
      solid organ transplants. METHOD: The sample included 72 adolescents who had
      received solid organ transplants. Multiple mediator models were tested via
      bootstrapping methods. RESULTS: Bivariate correlations revealed significant
      relationships between barriers and internalizing symptoms of depression, anxiety,
      and posttraumatic stress, as well as between internalizing symptoms and
      medication adherence. Barriers indicative of adaptation to the medication regimen
      (e.g., forgetting, lack of organization) were related to medication adherence and
      mediated the relationship between internalizing symptoms and medication
      adherence. CONCLUSIONS: These findings indicate that barriers may serve as a more
      specific factor in the relationship between more general, pervasive internalizing
      symptoms and medication adherence. Results may help guide areas for clinical
      assessment, and the focus of interventions for adolescent transplant recipients
      who are experiencing internalizing symptoms and/or who are nonadherent to their
      medication regimen.

PMID- 24080553
TI  - Another treatment option for keloids.

PMID- 24080554
TI  - Will screening open Pandora's box?

PMID- 24080555
TI  - Plantar fasciitis: How best to treat?
AB  - In addition to stretching exercises and orthotics, consider steroid injections as
      part of your first-line treatment options. For recalcitrant pain, a newer
      injectable reparative treatment is showing promise. 

PMID- 24080556
TI  - When to worry about incidental renal and adrenal masses.
AB  - Greater use of imaging has led to a corresponding rise in the detection of renal
      and adrenal incidentalomas-and left many primary care physicians unsure of what
      to do about the masses they've found.

PMID- 24080557
TI  - Hip fracture in older patients: tips and tools to speed recovery.
AB  - Delirium and VTE are among the many complications that can derail rehabilitation
      efforts. These tips can help you keep treatment on track. 

PMID- 24080558
TI  - Influenza: Update for the 2013-2014 season.
AB  - New vaccine products are available for this season, including a recombinant agent
      that has no egg protein. 

PMID- 24080559
TI  - This asthma treatment has a lasting side effect in children.
AB  - A new study finds that when children with asthma use inhaled corticosteroids, the
      effect on growth may not be temporary, as once thought. 

PMID- 24080560
TI  - Painful ear nodules.
AB  - Was there a connection between our patient's drug use and the appearance of his
      ears, which were turning black? 

PMID- 24080562
TI  - Bureaucracy leaves little time for acute care.

PMID- 24080561
TI  - Clinical Inquiry. Do dietary choices alone alter the risk of developing metabolic
      syndrome?

PMID- 24080563
TI  - A plea for acupuncture coverage.

PMID- 24080564
TI  - Recent onset of rash, dehydration, and nonbloody diarrhea in an elderly man.
AB  - A taste disturbance and anorexia accompanied his other symptoms. How would you
      proceed? 

PMID- 24080565
TI  - Consider this strategy for upper GI bleeds.
AB  - Patients with acute upper GI bleed are less likely to experience adverse events-
      and more likely to survive--when their care is governed by a restrictive
      transfusion policy. 

PMID- 24080566
TI  - Targeting systemic inflammation in patients with obesity-related pain: One
      practice's success with platelet-rich plasma therapy.
AB  - The 3 cases presented here represent the kind of success that one pain center is
      having with platelet-rich plasma therapy for the treatment of musculoskeletal
      pain. 

PMID- 24080567
TI  - Targeting systemic inflammation in patients with obesity-related pain: Neurogenic
      thoracic outlet syndrome: an often overlooked but treatable condition.
AB  - Rely primarily on a patient's history and your physical examination findings in
      considering the diagnosis. Physical therapy, tricyclic antidepressants or SNRIs,
      and botulinum toxin type A injections can help control symptoms. 

PMID- 24080568
TI  - Targeting systemic inflammation in patients with obesity-related pain: Obesity-
      related pain: time for a new approach that targets systemic inflammation.
AB  - We may be able to reduce pain, disability, and related comorbidities in obese
      patients by implementing modest weight loss and fitness interventions to address
      systemic inflammation. 

PMID- 24080569
TI  - Targeting systemic inflammation in patients with obesity-related pain: How best
      to prevent acute pain from becoming chronic?
AB  - The best approach is to find the individual risk factors and known predictors and
      manage them early on. 

PMID- 24080570
TI  - Integrating advances in insulin into clinical practice: Effective utilization of
      insulin in patient management.
AB  - The management of a patient with type 2 diabetes mellitus (T2DM) is typically a
      long-term process characterized by evolving strategies to meet and maintain the
      patient's glycemic, cardiovascular, lifestyle, and other goals. 

PMID- 24080571
TI  - Integrating advances in insulin into clinical practice. Introduction.
AB  - The prevalence of diabetes mellitus continues to rise in the United States,
      increasing from an estimated 17.9 million people in 2003-2006 to 18.8 million in
      2010. Despite decreases in the prevalence of smoking, elevated cholesterol, and
      high blood pressure from 1988 to 2008, the number of people diagnosed with
      dysglycemia and obesity increased within the same timeframe. 

PMID- 24080572
TI  - Integrating advances in insulin into clinical practice: Overview of current
      insulin formulations.
AB  - Defects in both insulin secretion and function play a fundamental role in the
      pathophysiologic mechanisms underlying both type 1 diabetes mellitus (T1DM) and
      type 2 diabetes mellitus (T2DM). As the most physiologic treatment option
      available, insulin plays a central role in the management of patients with T1DM
      and a growing role in the management of patients with T2DM, as is reflected in
      current treatment guidelines. 

PMID- 24080573
TI  - Integrating advances in insulin into clinical practice: Advances In insulin
      formulations.
AB  - The central role of insulin in the management of patients with type 1 diabetes
      mellitus (T1DM) remains, nearly a century after its first use in humans. In
      patients with type 2 diabetes mellitus (T2DM), the role of insulin has evolved as
      other therapies have been introduced, with insulin now used across the spectrum
      of the disease. This article discusses the use of insulin in patients with T1DM
      or T2DM, including combined use with other agents in T2DM, with an emphasis on
      incretin-based therapies. In addition, new insulin products and concentrations
      are discussed along with their varied routes of administration. 

PMID- 24080574
TI  - Palmitic acid increases medial calcification by inducing oxidative stress.
AB  - BACKGROUND: Aortic medial calcification is a cellular-regulated process leading
      to arterial stiffness. Although epidemiological studies have suggested an
      association between the saturation of fatty acids (FA) and arterial stiffness,
      there is no evidence that saturated FA can induce arterial calcification. This
      study investigated the capacity of palmitic acid (PA) to induce medial
      calcification and the signaling pathway(s) implicated in this process. METHODS:
      Rat aortic segments and vascular smooth muscle cells (VSMC) were exposed to
      calcification medium supplemented with PA. In vivo, rats were treated with
      warfarin to induce calcification and fed a PA-enriched diet. RESULTS: In vitro
      and ex vivo, palmitate increases calcification and ROS production. Palmitate
      increases extracellular-signal-regulated kinase (ERK1/2) phosphorylation and
      osteogenic gene expression. Inhibition of NADPH oxidase with apocynin or an siRNA
      prevents these effects. ERK1/2 inhibition attenuates the amplification of
      osteogenic gene expression and calcification induced by palmitate. In vivo, a PA
      enriched diet amplified medial calcification and pulse wave velocity (PWV). These
      effects are mediated by ROS production as indicated by the inhibition of
      calcification and PWV normalization in rats concomitantly treated with apocynin.
      CONCLUSION: ROS induction by palmitate leads to ERK1/2 phosphorylation and
      subsequently induces the osteogenic differentiation of VSMC. (c) 2013 S. Karger
      AG, Basel.

PMID- 24080575
TI  - Synthesis, molecular structure, DNA interaction and antioxidant activity of novel
      naphthoxazole compound.
AB  - A novel naphthoxazole compound 1 was synthesized and characterized. The crystal
      structure of the compound shows that N atom locates at beta-position and oxygen
      atom at alpha-position in naphthalene cycle. The DNA binding was studied by
      absorption spectroscopy, viscosity and luminescence spectra. The DNA binding
      constant was determined to be 6.16*10(3). The stoichiometry of compound/DNA is
      1:1. The pBR322 DNA cleavage induced by the compound was investigated. The
      antioxidant activity of the compound against hydroxyl radical was also explored. 

PMID- 24080576
TI  - Spectral studies on the interaction between HSSC and apoCopC.
AB  - The interaction between HSSC (SSC = salicylaldehyde semicarbazone anion) and
      apoCopC has been investigated in detail by means of UV, fluorescence and
      fluorescence lifetime measurement in 10 mM Hepes buffer, at pH 7.4, 25 degrees C.
      The results suggested that HSSC can form a novel supramolecular system with
      apoCopC, which can form a 1:1 host-guest inclusion supramolecular complex with
      HSSC, and the forming constant had been calculated to be (8.83+/-0.32)*10(5) M(
      1). It suggested the strong inclusion ability of apoCopC to the guest molecules.
      In addition, the stoichiometric ratio of Cu(2+) and HSSC was 1:1, which was the
      same as Cu(2+) and apoCopC. However, the binding ability between Cu(2+) and HSSC
      was much weaker than that between Cu(2+) and apoCopC. Moreover, the binding
      ability of HSSC with Cu(2+) has an effect on the binding ability between HSSC and
      apoCopC, and vice versa. The reason attributed to this effect was that the
      formation of hydrogen bond between Met46 in apoCopC and the phenolic hydroxyl of
      HSSC participated in the copper coordination. Furthermore, it was also found that
      HSSC quench the fluorescence of apoCopC by the static quenching process and the
      number of binding site was calculated. The thermodynamic parameters DeltaH
      degrees , DeltaS degrees  and DeltaG degrees  at different temperatures were
      obtained. The formation of apoCopC-HSSC complex depended on the cooperation of
      the van der Waals force and hydrogen bond, and the binding average distance
      between apoCopC and HSSC was determined. What is more, the binding site of HSSC
      to apoCopC was shown vividly by an automated public domain software package
      ArgusLab 4.0.1.

PMID- 24080577
TI  - FT-Raman study of deferoxamine and deferiprone exhibits potent amelioration of
      structural changes in the liver tissues of mice due to aluminum exposure.
AB  - The present study inform the alterations on major biochemical constituents such
      as lipids, proteins, nucleic acids and glycogen along with phosphodiester
      linkages, tryptophan bands, tyrosine doublet, disulfide bridge conformations,
      aliphatic hydrophobic residue, and salt bridges in liver tissues of mice using
      Fourier transform Raman spectroscopy. In amide I, amide II and amide III, the
      area value significant decrease due structural alteration in the protein,
      glycogen and triglycerides levels but chelating agents DFP and DFO upturned it.
      Morphology changes by aluminium induced alterations and recovery by chelating
      agents within liver tissues known by histopathological examination.
      Concentrations of trace elements were found by ICP-OES. FT-Raman study was
      revealed to be in agreement with biochemical studies and demonstrate that it can
      successfully specify the molecular alteration in liver tissues. The tyrosyl
      doublet ratio I899/I831 decreases more in aluminum intoxicated tissues but
      treatment with DFP and DFO+DFP brings back to nearer control value. This
      indicates more variation in the hydrogen bonding of the phenolic hydroxyl group
      due to aluminum poisoning. The decreased Raman intensity ratio (I3220/I3400)
      observed in the aluminum induced tissues suggests a decreased water domain size,
      which could be interpreted in terms of weaker hydrogen-bonded molecular species
      of water in the aluminum intoxicated liver tissues. Finally, FT-Raman
      spectroscopy might be a useful tool for obtained successfully to indicate the
      molecular level changes. 

PMID- 24080578
TI  - Quantum chemical and experimental studies on the structure and vibrational
      spectra of an alkaloid--Corlumine.
AB  - The study concentrates on an important natural product, phthalide isoquinoline
      alkaloid Corlumine (COR) [(6R)-6-[(1S)-1,2,3,4-Tetrahydro-6,7-dimethoxy-2
      methylisoquinolin-1-yl] furo [3,4-e]-1,3-benzodioxol-8(6H)-one] well known to
      exhibit spasmolytic and GABA antagonist activity. It was fully characterized by a
      variety of experimental methods including vibrational spectroscopy (IR and
      Raman), thermal analysis (DSC), UV and SEM. For a better interpretation and
      analysis of the results quantum chemical calculations employing DFT were also
      performed. TD-DFT was employed to elucidate electronic properties for both
      gaseous and solvent environment using IEF-PCM model. Graphical representation of
      HOMO and LUMO would provide a valuable insight into the nature of reactivity and
      some of the structural and physical properties of the title molecule. The
      structure-activity relationship have been interpreted by mapping electrostatic
      potential surface (MEP), which is valuable information for the quality control of
      medicines and drug-receptor interactions. Stability of the molecule arising from
      hyper conjugative interactions, charge delocalisation has been analyzed using
      natural bond orbital (NBO) analysis. Computation of thermodynamical properties
      would help to have a deep insight into the molecule for further applications. 

PMID- 24080579
TI  - Spectral and quantum chemical studies on 1,3-bis(N(1)-4-amino-6
      methoxypyrimidinebenzenesulfonamide-2,2,4,4-ethane-1,2-dithiol)-2,4
      dichlorocyclodiphosph(V)azane and its erbium complex.
AB  - Novel 1,3-bis(N(1)-4-amino-6-methoxypyrimidine-benzenesulfonamide-2,2,4,4-ethane
      1,2-dithiol)-2,4-dichlorocyclodiphosph(V)azane (L), was prepared and their
      coordinating behavior towards the lanthanide ion Er(III) was studied. The
      structures of the isolated products are proposed based on elemental analyses, IR,
      UV-VIS., (1)H NMR, (13)C NMR, (31)P NMR, SEM, XRD, mass spectra, effective
      magnetic susceptibility measurements and thermogravimetric analysis (TGA).
      Computational studies have been carried out at the DFT-B3LYP/6-31G(d) level of
      theory on the structural and spectroscopic properties of L and its binuclear
      Er(III) complex. Different tautomers of the ligand were optimized at the ab
      initio DFT level. Keto-form structure is about 17.7 kcal/mol more stable than the
      enol form (taking zpe correction into account). Simulated IR frequencies were
      scaled and compared with that experimentally measured. TD-DFT method was used to
      compute the UV-VIS spectra which compared by the measured electronic spectra.

PMID- 24080580
TI  - FTIR study of protective action of deferoxamine and deferiprone on the kidney
      tissues of aluminum loaded mice.
AB  - The present study was designed to evaluate the FTIR spectra of the aluminum
      exposed kidney tissues and recovered by chelating agents DFO and DFP then showed
      significant alteration on the major biochemical constituents such as lipids,
      proteins and glycogen at molecular level. The significant increased in the peak
      area of glycogen from 0.006+/-0.001 to 0.187+/-0.032 may be the interruption of
      aluminum in the calcium metabolism and the reduced level of calcium. The peak
      area value of amide A significantly decreased from control (4.931+/-1.446) to
      aluminum (1.234+/-0.052), but improved by DFP and DFO+DFP from 2.658+/-0.153 to
      3.252+/-0.070 respectively. Amide I and amide II peak area values also decreased
      from 1.690+/-0.133 to 0.811+/-0.192 and 1.158+/-0.050 to 0.489+/-0.047 but
      treated with DFP and DFO+DFP significantly improved. This result suggests an
      alteration in the protein profile. The absence of Olefinic=CH stretching band,
      C=O stretching of triglycerides and ring breathing mode in the DNA bases in
      aluminum exposure kidney suggests an altered lipid levels. Treated with DFP and
      DFO+DFP mice were considerably increased in lipid peroxidative markers. Further,
      assessed the activities of enzymatic antioxidants and measured the levels of
      nonenzymatic antioxidants. Concentrations of trace elements were found by ICP
      OES. Histopathology of chelating agents treated kidney showed reduced renal
      damage in aluminum induced mice. Thus, histopathological findings confirmed the
      biochemical observations of this study. This results demonstrated that FTIR
      spectroscopy can be successfully applied to toxicological and biotoxicology
      studies.

PMID- 24080581
TI  - Fast detection of peroxidase (POD) activity in tomato leaves which infected with
      Botrytis cinerea using hyperspectral imaging.
AB  - Tomatoes are cultivated around the world and gray mold is one of its most
      prominent and destructive diseases. An early disease detection method can
      decrease losses caused by plant diseases and prevent the spread of diseases. The
      activity of peroxidase (POD) is very important indicator of disease stress for
      plants. The objective of this study is to examine the possibility of fast
      detection of POD activity in tomato leaves which infected with Botrytis cinerea
      using hyperspectral imaging data. Five pre-treatment methods were investigated.
      Genetic algorithm-partial least squares (GA-PLS) was applied to select optimal
      wavelengths. A new fast learning neural algorithm named extreme learning machine
      (ELM) was employed as multivariate analytical tool in this study. 21 optimal
      wavelengths were selected by GA-PLS and used as inputs of three calibration
      models. The optimal prediction result was achieved by ELM model with selected
      wavelengths, and the r and RMSEP in validation were 0.8647 and 465.9880
      respectively. The results indicated that hyperspectral imaging could be
      considered as a valuable tool for POD activity prediction. The selected
      wavelengths could be potential resources for instrument development. 

PMID- 24080582
TI  - Molecular structure, vibrational spectra, NBO analysis and molecular packing
      prediction of 3-nitroacetanilide by ab initio HF and density functional theory.
AB  - Quantum chemical calculations of geometries and vibrational wavenumbers of 3
      nitroacetanilide (C8H8N2O3) in the ground state were carried out by using ab
      initio HF and density functional theory (DFT/B3LYP) methods with 6-31+G(*) basis
      set. The -311++G(**) basis set is also used for B3LYP level. The scaled harmonic
      vibrational frequencies have been compared with experimental FT-IR spectra.
      Theoretical vibrational spectra of the title compound were interpreted by means
      of potential energies distributions (PEDs) using MOLVIB program. The theoretical
      spectrograms for IR spectra of the title compound have been constructed. The
      shortening of C-H bond length and the elongation of N-H bond length suggest the
      existence of weak C-H?O and N-H?O hydrogen bonds, which is confirmed by the
      natural bond orbital analysis. In addition, the crystal structure obtained by
      molecular mechanics belongs to the P2(1) space group, with lattice parameters
      Z=4, a=14.9989 A, b=4.0367 A, c=12.9913 A, rho=0.998 g cm(-3).

PMID- 24080583
TI  - Hypertension: Do calcium-channel blockers increase breast cancer risk?

PMID- 24080584
TI  - Antioxidative capacity in the fat body of Bombyx mori is increased following oral
      administration of 4-methylumbelliferone.
AB  - Plant sources of umbelliferones have tumor-inhibitory effects at the cellular
      level. However, their physiological functions in animals are largely unresolved.
      In this study, we provide evidence to show that 4-methylumbelliferone (4-MU)
      participates in the regulation of antioxidative capacity in the fat body of
      Bombyx mori, a tissue similar to mammalian liver in this model invertebrate.
      Larvae (3rd day of the 5th instar) were orally exposed to 4 mM 4-MU, an
      umbelliferone, which swiftly induced the generation of a large number of ROS
      (e.g. H2O2 increased 6 to 8-fold), and 4-MU was detected in the fat body 8 min
      after administration. In addition, the activities of CAT and GPx were up
      regulated 4 to 11-fold and 2 to 16-fold, respectively, and were helpful in
      defending fat body cells against oxidative injury in combination with NADPH.
      Furthermore, significant increases in the contents of T-AOC (up to approx. 2
      fold), antioxidants of ASAFR (by 2 to 4-fold) and GSH were detected.

PMID- 24080585
TI  - Long-term follow-up in patients with indeterminate Barrett esophagus.
AB  - BACKGROUND: Barrett esophagus (BE) is a major risk factor for adenocarcinoma of
      the distal esophagus. Reliable detection of BE during upper endoscopy is
      therefore mandatory. According to most guidelines, diagnosis of BE requires both
      endoscopy and histology for confirmation. However, since adenocarcinomas were
      also described in patients with indeterminate BE, i.e. endoscopic visible
      columnar metaplasia but no histological confirmation of goblet cells or vice
      versa, debate has risen on the risk of malignancy and the need for endoscopic
      surveillance in such patients. PATIENTS AND METHODS: The study was aimed to
      assess long-term follow-up data on 209 patients with indeterminate BE (on
      histopathology or endoscopy) initially examined between 1999 and 2000. Patients
      or referring physicians were contacted concerning the most recent endoscopic and
      histopathological results. RESULTS: Follow-up data could be assessed in 149/209
      patients (65.1%) after a mean follow-up period of 9.4 years (SD +/-2.4 years).
      Neoplasia was not reported for any patient. The previous endoscopic
      histopathological diagnoses could be confirmed in 3 patients only. In the group
      with endoscopic diagnosis of BE but no histopathological confirmation, BE was
      described histopathologically in 1 patient during follow-up. CONCLUSION:
      Persistence of indeterminate BE is poor during long-term follow up. The risk of
      cancer appears to be negligible. Hence, surveillance of these patients appears
      equivocal.

PMID- 24080586
TI  - Cangrelor versus clopidogrel in percutaneous coronary intervention: a systematic
      review and meta-analysis.
AB  - AIMS: Cangrelor is a new antiplatelet agent that has been used in percutaneous
      coronary intervention (PCI) with mixed results. We aimed to review the evidence
      on the efficacy of cangrelor in comparison to clopidogrel in reducing ischaemic
      endpoints at 48 hours in patients undergoing PCI in large randomised trials.
      METHODS AND RESULTS: In three large clinical trials involving 25,107
      participants, the risk of the primary composite efficacy endpoint of death, MI
      and ischaemia-driven revascularisation at 48 hours, (pooled OR 0.94; 95% CI: 0.77
      1.14, p=0.51, I2=68%), death from all cause (pooled OR 0.72, 95% CI: 0.36-1.43,
      p=0.34, I2=52%), myocardial infarction (pooled OR 0.94, 95% CI: 0.77-1.14,
      p=0.51, I2=68%) was not significantly different between cangrelor and
      clopidogrel. Likewise, severe or life-threatening bleeding was similar between
      cangrelor and clopidogrel (pooled OR 1.21, 95% CI: 0.70-2.12, p=0.50, I2=0%). The
      risk of stent thrombosis (pooled OR 0.59, 95% CI: 0.43-0.81, p=0.001, I2=0%), Q
      wave myocardial infarction (pooled OR 0.53, 95% CI: 0.30-0.92, p=0.02, I2=0%) and
      ischaemia-driven revascularisation (pooled OR 0.71, 95% CI: 0.52-0.98, p=0.04,
      I2=0%) was lower in the cangrelor group. CONCLUSIONS: Based on this meta
      analysis, we did not find any difference in the risk of the primary composite
      efficacy endpoint of all-cause death, ischaemia-driven revascularisation, and
      myocardial infarction at 48hours between cangrelor and clopidogrel use. Given
      that cangrelor was associated with a lower risk of stent thrombosis, ischaemia
      driven revascularisation and Q-wave myocardial infarction compared to
      clopidogrel, cangrelor can be considered as a suitable alternative during PCI.

PMID- 24080587
TI  - Healthy aging by staying selectively connected: a mini-review.
AB  - Cognitive neuroscience of the healthy aging human brain has thus far addressed
      age-related changes of local functional and structural properties of gray and
      white matter and their association with declining or preserved cognitive
      functions. In addition to these localized changes, recent neuroimaging research
      has attributed an important role to neural networks with a stronger focus on
      interacting rather than isolated brain regions. The analysis of functional
      connectivity encompasses task-dependent and -independent synchronous activity in
      the brain, and thus reflects the organization of the brain in distinct
      performance-relevant networks. Structural connectivity in white matter pathways,
      representing the integrity of anatomical connections, underlies the communication
      between the nodes of these functional networks. Both functional and structural
      connectivity within these networks have been demonstrated to change with aging,
      and to have different predictive values for cognitive abilities in older compared
      to young adults. Structural degeneration has been found in the entire cerebral
      white matter with greatest deterioration in frontal areas, affecting whole brain
      structural network efficiency. With regard to functional connectivity, both
      higher and lower functional coupling has been observed in the aging compared to
      the young brain. Here, high connectivity within the nodes of specific functional
      networks on the one hand, and low connectivity to regions outside this network on
      the other hand, were associated with preserved cognitive functions in aging in
      most cases. For example, in the language domain, connections between left
      hemisphere language-related prefrontal, posterior temporal and parietal areas
      were described as beneficial, whereas connections between the left and right
      hemisphere were detrimental for language task performance. Of note, interactions
      between structural and functional network properties may change in the course of
      aging and differentially impact behavioral performance in older versus young
      adults. Finally, studies using noninvasive brain stimulation techniques like
      transcranial direct current stimulation (tDCS) to simultaneously modulate
      behavior and functional connectivity support the importance of 'selective
      connectivity' of aging brain networks for preserved cognitive functions. These
      studies demonstrate that enhancing task performance by tDCS is paralleled by
      increased connectivity within functional networks. In this review, we outline the
      network perspective on healthy brain aging and discuss recent developments in
      this field.

PMID- 24080588
TI  - Molecular mechanisms of fatty acid synthase (FASN)-mediated resistance to anti
      cancer treatments.
AB  - Human FASN is the key enzyme required for de novo synthesis of fatty acids. Up
      regulated FASN expression has been reported in various human cancers and was
      thought to contribute to poor prognosis and recurrence of these cancers. Studies
      using model cell lines have indicated the role of FASN in both intrinsic and
      acquired drug and radiation resistance. Recent studies suggest that FASN may play
      an important role in regulating gene expression such as pro-apoptotic proteins
      and cellular processes such as DNA repair pathways, which in turn contribute to
      resistance to drug and radiation-induced apoptosis. In this review, we will
      highlight our recent progress in understanding the mechanism of FASN-induced
      resistance. 

PMID- 24080589
TI  - The role of splicing factor mutations in the pathogenesis of the myelodysplastic
      syndromes.
AB  - Accurate pre-mRNA splicing by the spliceosome is a fundamental cellular mechanism
      required to remove introns that are present in most protein-coding transcripts.
      The recent discovery of a variety of somatic spliceosomal mutations in the
      myelodysplastic syndromes (MDS), a heterogeneous group of myeloid malignancies,
      has revealed a new leukemogenic pathway involving spliceosomal dysfunction.
      Spliceosome mutations are found in over half of all MDS patients and are likely
      founder mutations. The spliceosome mutations are highly specific to MDS and
      closely related conditions and, to some extent, appear to define distinct
      clinical phenotypes in MDS. The high frequency of mutations in different
      components of the RNA splicing machinery in MDS suggests that abnormal RNA
      splicing is the common consequence of these mutations. The identification of the
      downstream targets of the spliceosome mutations is an active area of research.
      Emerging data from the study of the MDS transcriptome suggests that spliceosomal
      mutations have effects on specific genes, including some previously shown to play
      a role in MDS pathogenesis. The effects of the spliceosomal mutations on RNA
      splicing and cell growth have been evaluated only in a limited context to date,
      however, and the determination of the impact of these mutations in primary human
      hematopoietic cells is essential in order to elucidate fully the molecular
      mechanism by which they contribute to MDS pathogenesis. 

PMID- 24080590
TI  - Genetic association with response to intravitreal ranibizumab for neovascular age
      related macular degeneration in the Han Chinese population.
AB  - PURPOSE: To investigate a possible association between gene variants and patient
      response to treatment with intravitreal ranibizumab for neovascular age-related
      macular degeneration (AMD). METHODS: Visual acuity score (VAS) was recorded at
      baseline and a subsequent visit at 6 months. Genotypes of 3 polymorphisms in
      known AMD susceptibility loci (rs1061170 in complement factor H (CFH), rs11200638
      in HTRA1 and rs1413711 in VEGF) were determined. Central retinal thickness and
      maximum thickness of the lesion were also measured. RESULTS: A total of 168
      neovascular AMD patients treated with intravitreal ranibizumab were included in
      our study. For HTRA1 rs11200638, mean VAS changes were 3.5, 9.4 and 10.6 letters
      for the AA, AG and GG genotypes, respectively (p = 0.022). In contrast, for CFH
      rs1061170 and VEGF rs1413711, mean VAS changes were not significant. However,
      there was no significant difference in the changes in central retinal thickness
      and maximum lesion thickness among the genotypes of the tested single-nucleotide
      polymorphisms. CONCLUSIONS: HTRA1 gene polymorphism may influence patient
      response to treatment with intravitreal ranibizumab for neovascular AMD.

PMID- 24080591
TI  - Facile synthesis of a new fluorogenic metal scavenging interpolymeric diamide
      based on cellulose and alginic acids.
AB  - A microwave assisted synthesis of a water soluble fluorogenic interpolymeric
      diamide has been described involving alginic acid and polyglucuronic acid (PGA)
      amide of ethylenediamine (EDA), through a monoamide of PGA and EDA, in good
      yields (>80wt% in each step). PGA was prepared by TEMPO (2,2,6,6-tetramethyl
      piperidine-1-oxyl radical) mediated oxidation of cellulose of the halophytic
      plant Salicornia brachiata. The amides were characterized by spectral analyses.
      The fluorescence emission of the PGA amide was 7-fold greater than that of the
      interpolymeric diamide. PGA monoamide exhibited superior heavy metal ions [Pb(II)
      and Hg(II)] uptake properties to the diamide, the former showing optimum
      adsorptions of ions 398.8 and 282.8mg/g, respectively. These materials may be of
      utility as potential sensors harnessing their fluorogenic and metal scavenging
      properties. 

PMID- 24080592
TI  - Effect of simvastatin on hemostasis in patients with isolated
      hypertriglyceridemia.
AB  - BACKGROUNDS/AIMS: Elevated triglyceride levels seem to predispose to the earlier
      development and accelerated progression of coronary artery disease. In our study,
      we assessed for the first time whether simvastatin treatment affects coagulation
      and fibrinolysis in patients with isolated hypertriglyceridemia. METHODS: The
      study included 39 patients with elevated triglyceride levels and peripheral
      artery sclerosis, treated for 90 days with either simvastatin (40 mg daily) or
      placebo. Plasma lipids, glucose homeostasis markers and hemostasic variables were
      assessed at baseline and after treatment. RESULTS: Simvastatin, but not placebo,
      administered to these patients reduced plasma levels/activity of fibrinogen (from
      3.5 +/- 0.4 to 2.8 +/- 0.3 g/l, p < 0.01), factor VII (from 144.2 +/- 16.9 to
      112.5 +/- 14.0%, p < 0.01) and plasminogen activator inhibitor-1 (from 76.9 +/-
      13.5 to 50.2 +/- 9.2 ng/ml, p < 0.001), without a significant reduction in von
      Willebrand factor levels, and tended to prolong the prothrombin and partial
      thromboplastin times. CONCLUSION: Our results suggest that statin treatment
      produces a multidirectional effect on coagulation and fibrinolysis in patients
      with isolated hypertriglyceridemia and that this treatment may bring some
      benefits to patients with elevated triglyceride levels.

PMID- 24080593
TI  - Transmission of Mycobacterium tuberculosis in a High School and School-Based
      Supervision of an Isoniazid-Rifapentine Regimen for Preventing Tuberculosis -
      Colorado, 2011-2012.
AB  - Mycobacterium tuberculosis, the bacterium that causes tuberculosis (TB), is
      spread from person to person by the airborne route. It can be transmitted
      extensively in congregate settings, making investigating exposures and treating
      infected contacts challenging. In December 2011, a student at a Colorado high
      school with 1,381 students and school personnel received a diagnosis of pulmonary
      TB disease. One of five household contacts had TB disease, and the other four had
      latent M. tuberculosis infection (LTBI). Screening of 1,249 school contacts (90%)
      found one person with pulmonary TB disease, who was fully treated, and 162 with
      LTBI, of whom 159 started an LTBI treatment regimen for preventing progression to
      TB disease and 153 completed a regimen. Only the index patient required inpatient
      care for TB, and TB caused no deaths. Use of short-course treatment regimens,
      either 12-dose weekly isoniazid and rifapentine directly observed at school or 4
      months of self-supervised rifampin daily, facilitated treatment completion. State
      and county incident command structures led by county TB control authorities
      guided a response team from multiple jurisdictions. News media reports brought
      public scrutiny, but meetings with the community addressed the concerns and
      enhanced public participation. Two contacts of the index patient outside of the
      school had TB disease diagnosed after the school investigation. As of July 2013,
      no additional TB disease associated with in-school exposure had been found. An
      emergency plan for focusing widespread resources, an integral public
      communications strategy, and new, efficient interventions should be considered in
      other large TB contact investigations. 

PMID- 24080594
TI  - Estimating meningitis hospitalization rates for sentinel hospitals conducting
      invasive bacterial vaccine-preventable diseases surveillance.
AB  - The World Health Organization (WHO)-coordinated Global Invasive Bacterial Vaccine
      Preventable Diseases (IB-VPD) sentinel hospital surveillance network provides
      data for decision making regarding use of pneumococcal conjugate vaccine and
      Haemophilus influenzae type b (Hib) vaccine, both recommended for inclusion in
      routine childhood immunization programs worldwide. WHO recommends that countries
      conduct sentinel hospital surveillance for meningitis among children aged <5
      years, including collection of cerebrospinal fluid (CSF) for laboratory detection
      of bacterial etiologies. Surveillance for pneumonia and sepsis are recommended at
      selected hospitals with well-functioning laboratories where meningitis
      surveillance consistently meets process indicators (e.g., surveillance
      performance indicators). To use sentinel hospital surveillance for meningitis to
      estimate meningitis hospitalization rates, WHO developed a rapid method to
      estimate the number of children at-risk for meningitis in a sentinel hospital
      catchment area. Monitoring changes in denominators over time using consistent
      methods is essential for interpreting changes in sentinel surveillance incidence
      data and for assessing the effect of vaccine introduction on disease
      epidemiology. This report describes the method and its use in The Gambia and
      Senegal. 

PMID- 24080595
TI  - Long-term results of anterior versus posterior operations for herniated cervical
      discs: analysis of 6,000 patients.
AB  - OBJECTIVE: To analyze the long-term outcomes of anterior versus posterior
      approaches for cervical disc herniation. METHODS: The records of 6,000 patients
      who had operations for cervical disc herniation (radiating arm pain and/or motor
      symptoms involving the upper extremity) and who had been followed for at least 2
      years (mean: 7.1 years) were culled from the world literature and included in
      this analysis. The outcome (good/excellent, according to the patient) of anterior
      versus posterior surgery was compared. RESULTS: Of the 6,000 patients, 2,888
      (48.1%) had anterior operations (anterior cervical discectomies, with or without
      fusion) and 3,112 (51.9%) patients were operated on posteriorly
      (laminoforaminotomies/'keyhole' facetectomies). Although initially equal, in long
      term follow-up, patients who had anterior operations had 80% good/excellent
      results, whereas patients with the posterior approach had 94% good/excellent
      results. The difference was significant (p < 0.05). CONCLUSION: The better long
      term results with the posterior operation might be due to the more complete
      opening of the foramen for neural decompression at the time of the operation and
      thereafter.

PMID- 24080596
TI  - Combined serum creatinine and cystatin C Schwartz formula predicts kidney
      function better than the combined CKD-EPI formula in children.
AB  - BACKGROUND: The combined serum creatinine (SCreat) and cystatin C (CysC) CKD-EPI
      formula constitutes a new advance for glomerular filtration rate (GFR) estimation
      in adults. Using inulin clearances (iGFRs), the revised SCreat and the combined
      Schwartz formulas, this study aims to evaluate the applicability of the combined
      CKD-EPI formula in children. METHOD: 201 iGFRs for 201 children were analyzed and
      divided by chronic kidney disease (CKD) stages (iGFRs >=90 ml/min/1.73 m(2), 90 >
      iGFRs > 60, and iGFRs <=59), and by age groups (<10, 10-15, and >15 years).
      Medians with 95% confidence intervals of bias, precision, and accuracies within
      30% of the iGFRs, for all three formulas, were compared using the Wilcoxon signed
      rank test. RESULTS: For the entire cohort and for all CKD and age groups, medians
      of bias for the CKD-EPI formula were significantly higher (p < 0.001) and
      precision was significantly lower than the solely SCreat and the combined SCreat
      and CysC Schwartz formulas. We also found that using the CKD-EPI formula, bias
      decreased and accuracy increased while the child age group increased, with a
      better formula performance above 15 years of age. However, the CKD-EPI formula
      accuracy is 58% compared to 93 and 92% for the SCreat and combined Schwartz
      formulas in this adolescent group. CONCLUSIONS: The performance of the combined
      CKD-EPI formula improves in adolescence compared with younger ages. Nevertheless,
      the CKD-EPI formula performs more poorly than the SCreat and the combined
      Schwartz formula in pediatric population.

PMID- 24080597
TI  - Enriched cages for groups of laboratory male rats and their effects on behaviour,
      weight gain and adrenal glands.
AB  - We investigated if there were any negative effects on the behaviour and
      physiology of rats housed in groups of five in two types of enriched cages and
      compared them with paired-housed rats housed in traditional cages. Eighty-four
      male Wistar and Sprague-Dawley rats were housed in an enriched rat cage (ERC), a
      rebuilt rabbit cage (RRC) or a Makrolon III cage (MC) system from 5-16 weeks of
      age with access to different enrichments. Recordings of behaviour and cage use (3
      * 24 h video recording), weekly weighing, measuring food consumption four
      days/week and water consumption two days/week, were carried out. The rats' muscle
      strength was assessed using the 'inclined plane' at the end of the study, and
      after euthanasia the adrenal glands were removed and weighed. Being in the
      shelter was the most common behaviour in the ERC and RRC groups. In the MC group,
      which lacked a shelter, rats performed the highest percentage of lying, grooming,
      rearing, play fighting and manipulating paper shreds. Rats in the RRC had the
      highest percentage of standing and manipulating gnawing sticks. Water consumption
      was higher in MC than in ERC and RRC rats. Rats from the RRC managed to remain at
      a steeper angle on the 'inclined plane' than rats from the MC. There were no
      significant effects of cage type on weight gain, food consumption or relative
      weights of adrenal glands. In conclusion, male rats kept in groups of five in
      larger enriched cages benefited from the enrichments, and no negative effects
      were found in the larger groups. 

PMID- 24080599
TI  - Gastrointestinal cancer: AVEX: opportunities in elderly patients with mCRC.

PMID- 24080600
TI  - Reproducibility of research and preclinical validation: problems and solutions.
AB  - Lack of reproducibility in the scientific and lay literature of many scientific
      reports is an increasing concern, as are the high rates of failure to validate
      highly promising preclinical observations in clinical trials. There are many
      technical reasons why experimental results, particularly in cancer research,
      cannot be reproduced, including unrecognized variables in the complex
      experimental model, poor documentation of procedures, selective reporting of the
      most-positive findings, misinterpretation of technical noise as biological signal
      and, in the most extreme cases, fabrication of data. We suggest that cognitive
      biases in research and flaws in the academic incentive system also contribute to
      the publication of immature results. Recognition of these factors, which are
      often not discussed, provides additional strategies to improve reproducibility.
      We suggest that in addition to establishing better standards of data presentation
      and creating venues for publication of negative results, some changes to the
      grant submission and funding system could further improve the reproducibility of
      research findings.

PMID- 24080601
TI  - Dorsolumbosacral agenesis, nonterminal myelocystocele and secondary tonsillar
      herniation: prenatal and postnatal MRI evaluation and pathological correlation.
AB  - We present a complex case of dorsolumbosacral agenesis associated with a
      nonterminal myelocystocele and secondary tonsillar herniation. The secondary
      tonsillar herniation, mimicking a Chiari I malformation, was evident at postnatal
      life with concomitant enlargement of the myelocystocele. Prenatal and postnatal
      MRI proved invaluable in recognizing temporal change in the position of the
      cerebellar tonsils. Postmortem examination confirmed the presence of a
      nonterminal myelocystocele and dorsolumbosacral agenesis.

PMID- 24080607
TI  - New harmonic scalpel versus conventional hemostasis in right colon surgery: a
      prospective randomized controlled clinical trial.
AB  - BACKGROUND: The Harmonic Scalpel (HS) is a device that uses vibrations to
      coagulate and cut tissues simultaneously. Its advantages are represented by
      minimal lateral thermal tissue damage, less smoke formation, no neuromuscular
      stimulation and no transmission of electricity to the patient. METHODS: A total
      of 211 consecutive patients (113 men, 98 women; mean age 64 years) undergoing
      hemicolectomy for cancer of the right colon were divided into two groups, namely
      those in whom the operation was performed using a new HS handpiece (NHS; 108
      patients) and those assigned to conventional hemostasis (CH; 103 patients). The
      two surgical groups were compared regarding patients' age and sex, tumor size,
      location, histotype and local invasiveness assessed by American Joint Cancer
      Committee stage, operative time, fluid content in the suction balloon (drainage
      volume) during the first 1-3 days after surgery, hospital stay and complications.
      RESULTS: Ultrasonic energy delivered through an HS has been shown to be safe and
      to produce minimal damage to the surrounding tissues because of its minimal heat
      production. Electrical devices allow hemostatic control in vessels up to 3 mm in
      diameter, while HS can coagulate vessels up to 5 mm in diameter; thus, HS allows
      not only better control of bleeding but also of lymphorrhea. In fact, the amount
      of fluid collected in the drainage was significantly lower in the NHS group
      compared to the CH group. Protein depletion influences the patient's regenerative
      capacity and thus also the occurrence of complications and recovery time.
      CONCLUSION: NHS is a useful device in colon surgery; it facilitates surgical
      maneuvers and reduces operative times and blood and lymphatic losses, allowing
      satisfactory maintenance of protein storage. This results in a lower incidence of
      complications and faster recovery by patients.

PMID- 24080598
TI  - Beyond aspirin-cancer prevention with statins, metformin and bisphosphonates.
AB  - Cancer risk reduction using pharmacological means is an attractive modern
      preventive approach that supplements the classical behavioural prevention
      recommendations. Medications that are commonly used by large populations to treat
      a variety of common, non-cancer-related, medical situations are an attractive
      candidate pool. This Review discusses three pharmacological agents with the most
      evidence for their potential as cancer chemopreventive agents: anti
      hypercholesterolaemia medications (statins), an antidiabetic agent (metformin)
      and antiosteoporosis drugs (bisphosphonates). Data are accumulating to support a
      significant negative association of certain statins with cancer occurrence or
      survival in several major tumour sites (mostly gastrointestinal tumours and
      breast cancer), with an augmented combined effect with aspirin or other non
      steroidal anti-inflammatory drugs. Metformin, but not other hypoglycaemic drugs,
      also seems to have some antitumour growth activity, but the amount of evidence in
      human studies, mainly in breast cancer, is still limited. Experimental and
      observational data have identified bisphosphonates as a pharmacological group
      that could have significant impact on incidence and mortality of more than one
      subsite of malignancy. At the current level of evidence these potential
      chemopreventive drugs should be considered in high-risk situations or using the
      personalized approach of maximizing individual benefits and minimizing the
      potential for adverse effects with the aid of pharmacogenetic indicators. 

PMID- 24080608
TI  - Impact of added fluvastatin to standard-of-care treatment on sustained
      virological response in naive chronic hepatitis C Patients infected with
      genotypes 1 and 3.
AB  - OBJECTIVES: The combination of pegylated interferon-alpha and ribavirin is a
      standard-of-care (SOC) treatment for chronic hepatitis C (CHC), and it achieves a
      sustained virological response (SVR) in 41-52% of genotype 1 and in 73-79% of
      genotype 3 patients. In a few clinical trials, the combination of fluvastatin and
      SOC increased the SVR in genotype 1 patients. METHODS: This prospective study
      enrolled 179 naive CHC patients. In the fluvastatin group patients received the
      combination of SOC and fluvastatin 80 mg daily; historical controls matching the
      study group in genotype, age and gender were treated with the SOC treatment only.
      RESULTS: On-treatment viral responses as well as the SVR did not differ
      significantly between the two groups, except for the genotype 1 patients with a
      high viral load presenting a significantly higher SVR rate in the fluvastatin
      group (75%) compared to the control group (41%; p = 0.024). Multivariate logistic
      regression identified hepatitis C virus (HCV) genotype 3 infection (p < 0.001),
      age <=40 years (p < 0.001), liver steatosis <5% (p < 0.01) and low viral load (p
      < 0.001) as independent predictors of an SVR. CONCLUSION: A combination of
      fluvastatin and SOC significantly improved the SVR in naive CHC patients infected
      with HCV genotype 1 and high viral load, but it did not improve the SVR in
      patients infected with HCV genotype 3.

PMID- 24080609
TI  - Prediction of malignancy in cystic neoplasms of the pancreas: a population-based
      cohort study.
AB  - OBJECTIVES: Pancreatic cystic neoplasms (PCNs) are being detected with increased
      frequency. The aims of this study were to determine the incidence of malignancy
      and develop an imaging-based system for prediction of malignancy in PCN. METHODS:
      We conducted a retrospective cohort study of patients >=18 years of age with
      confirmed PCN from January 2005 to December 2010 in a community-based integrated
      care setting in Southern California. Patients with history of acute or chronic
      pancreatitis were excluded. Malignancy diagnosed within 3 months of cyst
      diagnosis was considered as pre-existing. Subsequent incidence of malignancy
      during surveillance was calculated based on person-time at risk. Age- and gender
      adjusted standardized incidence ratio (SIR) was calculated with the non-cyst
      reference population. Recursive partitioning was used to develop a risk
      prediction model based on cyst imaging features. RESULTS: We identified 1,815
      patients with confirmed PCN. A total of 53 (2.9%) of patients were diagnosed with
      cyst-related malignancy during the study period. The surveillance cohort
      consisted of 1,735 patients with median follow-up of 23.4 months. Incidence of
      malignancy was 0.4% per year during surveillance. The overall age- and gender
      adjusted SIR for pancreatic malignancy was 35.0 (95% confidence level 26.6,
      46.0). Using recursive partitioning, we stratified patients into low (<1%),
      intermediate (1-5%), and high (9-14%) risk of harboring malignant PCN based on
      four cross-sectional imaging features: size, pancreatic duct dilatation,
      septations with calcification as well as growth. Area under the receiver operator
      characteristic curve for the prediction model was 0.822 (training) and 0.808
      (testing). CONCLUSIONS: Risk of pancreatic malignancy was lower than previous
      reports from surgical series but was still significantly higher than the
      reference population. A risk stratification system based on established imaging
      criteria may help guide future management decisions for patients with PCN.

PMID- 24080610
TI  - Naringin exhibits in vivo prokinetic activity via activation of ghrelin receptor
      in gastrointestinal motility dysfunction rats.
AB  - BACKGROUND AND PURPOSE: Poncirus fructus (PF), also known as the dried immature
      fruit of Poncirus trifoliata (L.) Raf., has long been used as a cure for the
      treatment of various gastrointestinal disorders in eastern Asia. Recently, it was
      reported that naringin, a flavonoid constituent of the PF extract, causes the
      activation of ghrelin receptor in vitro. Although the ghrelin receptor is
      involved in the enhancement of intestinal motility, there are no studies as yet
      involving in vivo action of naringin. Therefore, the purpose of the present study
      is to investigate whether naringin exhibits a prokinetic effect in vivo. METHODS:
      We measured the intestinal transit rate in rats with gastrointestinal motility
      dysfunction (GMD) and performed a pharmacokinetic analysis of naringin to
      investigate the effect of naringin on prokinetic activity in vivo. RESULTS: The
      results of this study show that the aqueous extract of PF and its constituent
      naringin have a strong prokinetic activity in GMD rats via activation of the
      ghrelin receptor. Surprisingly, pharmacokinetic analysis revealed that naringin
      has low bioavailability (11%), implying that the prokinetic effect of naringin
      was largely due to the local activation of ghrelin receptor in the intestine
      rather than a systemic effect after absorption. Indeed, it turned out that
      intravenous administration of naringin led to a lower prokinetic effect than when
      administrated orally to rats, indicating that naringin prefers to act on the
      intestinal wall rather than getting absorbed into the systemic circuit. This
      local mode of action might be advantageous for preventing possible systemic side
      effects since naringin is not well absorbed into the system circuit. CONCLUSIONS:
      Naringin exhibits an in vivo prokinetic activity by a preferable local activation
      of ghrelin receptor. Moreover, we propose that naringin could play a role as a
      leading compound for the development of ghrelin receptor-based prokinetic agents.

PMID- 24080611
TI  - Experimental and clinical findings regarding matrix metalloproteinases in
      cardiovascular diseases.

PMID- 24080612
TI  - The emetophobia questionnaire (EmetQ-13): psychometric validation of a measure of
      specific phobia of vomiting (emetophobia).
AB  - This study reports on the development and psychometric evaluation of a self
      report assessment of the severity of symptoms of emetophobia. Using a sample of
      95 individuals with emetophobia, and a matched sample of 90 control participants,
      a 13-items inventory was developed that showed a clear three-factor structure.
      The EmetQ-13 had good internal consistency (alpha=.82 in the clinical sample, and
      alpha=.85 in the control sample), and one-week test-retest reliability (rxx=.76).
      The EmetQ-13 showed significant correlations with another measure of emetophobia
      symptoms, the Specific Phobia of Vomiting Inventory, and related constructs such
      as disgust sensitivity. The measure showed excellent ability to classify
      emetophobic and non-emetophobic individuals, with correct assignment in 96.2% of
      cases. The EmetQ-13 also correlated significantly with a behavioural approach
      test using a vomit-like stimulus. The initial evaluation of the EmetQ-13 suggests
      that it is a reliable and valid measure for the assessment of emetophobia. 

PMID- 24080613
TI  - Prognostic factors of 'high-grade' Ta bladder cancers according to the WHO 2004
      classification: are these equivalent to 'high-risk' non-muscle-invasive bladder
      cancer?
AB  - OBJECTIVE: To determine the impact of prognostic factors of a series of high
      grade Ta non-muscle-invasive bladder cancers (NMIBCs) according to the new
      International Society of Urological Pathology (ISUP) 1998/WHO 2004 grading system
      (previously classified as either TaG2 or TaG3). METHODS: One hundred and thirty
      one high-grade Ta (105 G2 and 26 G3) cases were identified after independent
      review by two pathologists. Univariable and multivariable Cox regression models
      addressed recurrence and progression-free survival. Progression was defined as
      appearance of any T >=1 recurrence after complete TUR (type 1) or occurrence of T
      >=2 (type 2). RESULTS: Ten-year recurrence, type-1 and type-2 progression-free
      survival were 60, 75 and 95%, respectively. The previous grading system (G3 vs.
      G2) significantly predicted type 1 progression in the univariate model only. In
      the multivariate model, Ki67 was the only independent predictor of progression
      according to both definitions (HR = 5.25, p = 0.002 and HR = 6.16, p = 0.03,
      respectively). CONCLUSIONS: High-grade Ta NMIBC as defined by the WHO 2004
      grading system cannot be equated with high-risk NMIBC. The risk of progression to
      muscle-invasive disease (type 2) is low, more in keeping with an intermediate
      risk category of NMIBC. The previous WHO 1973 subcategorization into G2 and G3 is
      of little help in the prediction of outcome. Ki67 is a strong independent
      predictor of progression worthy of consideration for a clinical setting.

PMID- 24080614
TI  - Sociodemographic and lifestyle determinants of functional food consumption in an
      adult population of the Balearic Islands.
AB  - BACKGROUND/AIMS: Studies about functional food (FF) consumption among south
      Europeans are scarce. The aim of this study was to assess sociodemographic and
      lifestyle determinants of FF consumption in adult inhabitants of the Balearic
      Islands. METHODS: A population-based, cross-sectional, nutritional survey was
      conducted. The target population consisted of all inhabitants aged 16-65 years
      living in the Balearic Islands. FFs were selected from a semiquantitative food
      frequency questionnaire. Sociodemographic and lifestyle characteristics were also
      assessed. RESULTS: A high percentage of the population consumed FFs (skimmed
      milk, fiber-rich bread/cookies, probiotics, breakfast cereals and tea). Gender
      was a significant determinant for FF consumption. Females were more likely to
      consume soy milk, fiber-rich bread/cookies and tea; males preferred to consume
      breakfast cereals. FF consumption was significantly associated with increasing
      age in both genders. Fiber-rich bread/cookies were especially consumed by
      individuals with medium education, and breakfast cereals were consumed by
      respondents with a medium income. Physically active adults were more likely to
      consume soy milk, breakfast cereals, probiotics and red wine, and obese
      individuals were less likely to consume breakfast cereals and fiber-rich
      bread/cookies. CONCLUSIONS: A high percentage of the study population consumed
      FFs. Gender, age, marital status, education level, body mass index and physical
      activity are factors associated with FF consumption.

PMID- 24080615
TI  - Water security in one blue planet: twenty-first century policy challenges for
      science.
AB  - Water-related risks threaten society at the local, national and global scales in
      our inter-connected and rapidly changing world. Most of the world's poor are
      deeply water insecure and face intolerable water-related risks associated with
      complex hydrology. Most of the world's wealthy face lower water-related risks and
      less complex hydrology. This inverse relationship between hydrological complexity
      and wealth contributes to a divided world. This must be addressed if global water
      security is to be achieved. Using a risk-based framework provides the potential
      to link the current policy-oriented discourse on water security to a new and
      rigorous science-based approach to the description, measurement, analysis and
      management of water security. To provide the basis for this science-based
      approach, we propose an encompassing definition rooted in risk science: water
      security is a tolerable level of water-related risk to society. Water security
      policy questions need to be framed so that science can marshal interdisciplinary
      data and evidence to identify solutions. We join a growing group of scientists in
      asserting a bold vision for science leadership, calling for a new and
      comprehensive understanding of the planet's water system and society's water
      needs. 

PMID- 24080616
TI  - Risk-based principles for defining and managing water security.
AB  - The concept of water security implies concern about potentially harmful states of
      coupled human and natural water systems. Those harmful states may be associated
      with water scarcity (for humans and/or the environment), floods or harmful water
      quality. The theories and practices of risk analysis and risk management have
      been developed and elaborated to deal with the uncertain occurrence of harmful
      events. Yet despite their widespread application in public policy, theories and
      practices of risk management have well-known limitations, particularly in the
      context of severe uncertainties and contested values. Here, we seek to explore
      the boundaries of applicability of risk-based principles as a means of
      formalizing discussion of water security. Not only do risk concepts have
      normative appeal, but they also provide an explicit means of addressing the
      variability that is intrinsic to hydrological, ecological and socio-economic
      systems. We illustrate the nature of these interconnections with a simulation
      study, which demonstrates how water resources planning could take more explicit
      account of epistemic uncertainties, tolerability of risk and the trade-offs in
      risk among different actors. 

PMID- 24080617
TI  - Extreme rainfall, vulnerability and risk: a continental-scale assessment for
      South America.
AB  - Extreme weather continues to preoccupy society as a formidable public safety
      concern bearing huge economic costs. While attention has focused on global
      climate change and how it could intensify key elements of the water cycle such as
      precipitation and river discharge, it is the conjunction of geophysical and
      socioeconomic forces that shapes human sensitivity and risks to weather extremes.
      We demonstrate here the use of high-resolution geophysical and population
      datasets together with documentary reports of rainfall-induced damage across
      South America over a multi-decadal, retrospective time domain (1960-2000). We
      define and map extreme precipitation hazard, exposure, affectedpopulations,
      vulnerability and risk, and use these variables to analyse the impact of floods
      as a water security issue. Geospatial experiments uncover major sources of risk
      from natural climate variability and population growth, with change in climate
      extremes bearing a minor role. While rural populations display greatest relative
      sensitivity to extreme rainfall, urban settings show the highest rates of
      increasing risk. In the coming decades, rapid urbanization will make South
      American cities the focal point of future climate threats but also an opportunity
      for reducing vulnerability, protecting lives and sustaining economic development
      through both traditional and ecosystem-based disaster risk management systems. 

PMID- 24080618
TI  - Water security in the Canadian Prairies: science and management challenges.
AB  - In this paper, we discuss the multiple dimensions of water security and define a
      set of thematic challenges for science, policy and governance, based around cross
      scale dynamics, complexity and uncertainty. A case study of the Saskatchewan
      River basin (SRB) in western Canada is presented, which encompasses many of the
      water-security challenges faced worldwide. A science agenda is defined based on
      the development of the SRB as a large-scale observatory to develop the
      underpinning science and social science needed to improve our understanding of
      water futures under societal and environmental change. We argue that non
      stationarity poses profound challenges for existing science and that new
      integration of the natural sciences, engineering and social sciences is needed to
      address decision making under deep uncertainty. We suggest that vulnerability
      analysis can be combined with scenario-based modelling to address issues of water
      security and that knowledge translation should be coupled with place-based
      modelling, adaptive governance and social learning to address the complexity
      uncertainty and scale dynamics of contemporary water problems. 

PMID- 24080619
TI  - Growing water scarcity in agriculture: future challenge to global water security.
AB  - As water is an essential component of the planetary life support system, water
      deficiency constitutes an insecurity that has to be overcome in the process of
      socio-economic development. The paper analyses the origin and appearance of blue
      as well as green water scarcity on different scales and with particular focus on
      risks to food production and water supply for municipalities and industry. It
      analyses water scarcity originating from both climatic phenomena and water
      partitioning disturbances on different scales: crop field, country level and the
      global circulation system. The implications by 2050 of water scarcity in terms of
      potential country-level water deficits for food self-reliance are analysed, and
      the compensating dependence on trade in virtual water for almost half the world
      population is noted. Planetary-scale conditions for sustainability of the global
      water circulation system are discussed in terms of a recently proposed Planetary
      Freshwater Boundary, and the consumptive water use reserve left to be shared
      between water requirements for global food production, fuelwood production and
      carbon sequestration is discussed. Finally, the importance of a paradigm shift in
      the further conceptual development of water security is stressed, so that
      adequate attention is paid to water's fundamental role in both natural and socio
      economic systems. 

PMID- 24080620
TI  - The politics of African energy development: Ethiopia's hydro-agricultural state
      building strategy and clashing paradigms of water security.
AB  - As key economic, ecological and demographic trends converge to reshape Africa and
      its relationship with the outside world, a new politics is emerging in the twenty
      first century around the water-food-energy nexus, which is central to the
      continent's relevance in the global economy. On the one hand, Malthusian
      anxieties are proliferating; pessimists link population growth and growing water
      scarcity to state failure and 'water wars'. On the other hand, entrepreneurs,
      sovereign wealth funds and speculators consider Africa's potential in water
      resources, energy production and food output as one of the last great untapped
      opportunities for the global economy: Africa is on the brink of an agro
      industrial transformation. This article examines how African actors are not
      merely responding to economic and environmental changes but also thinking
      politically about water, food and energy security. Many of them are seizing the
      new opportunities to redefine their national politics, their relationship with
      local communities and their ties with external players, regionally and globally.
      Ethiopia's project of hydro-agricultural state-building helps to identify the
      most important fault lines of this new politics at the national, local and
      international level. The politics of water security and energy development
      simultaneously puts African states and their populations on the defensive, as
      they grapple with huge challenges, but also provides them with unique
      opportunities to take advantage of a more favourable global configuration of
      forces. 

PMID- 24080621
TI  - Water security, global change and land-atmosphere feedbacks.
AB  - Understanding the competing pressures on water resources requires a detailed
      knowledge of the future water balance under uncertain environmental change. The
      need for a robust, scientifically rigorous evidence base for effective policy
      planning and practice has never been greater. Environmental change includes, but
      is not limited to, climate change; it also includes land-use and land-cover
      change, including deforestation for agriculture, and occurs alongside changes in
      anthropogenic interventions that are used in natural resource management such as
      the regulation of river flows using dams, which can have impacts that frequently
      exceed those arising in the natural system. In this paper, we examine the role
      that land surface models can play in providing a robust scientific basis for
      making resource management decisions against a background of environmental
      change. We provide some perspectives on recent developments in modelling in land
      surface hydrology. Among the range of current land surface and hydrology models,
      there is a large range of variability, which indicates that the specification and
      parametrization of several basic processes in the models can be improved. Key
      areas that require improvement in order to address hydrological applications
      include (i) the representation of groundwater in models, particularly at the
      scales relevant to land surface modelling, (ii) the representation of human
      interventions such as dams and irrigation in the hydrological system, (iii) the
      quantification and communication of uncertainty, and (iv) improved understanding
      of the impact on water resources availability of multiple use through treatment,
      recycling and return flows (and the balance of consumptive and conservative
      uses). Through a series of examples, we demonstrate that changes in water use
      could have important reciprocal impacts on climate over a wide area. The effects
      of water management decisions on climate feedbacks are only beginning to be
      investigated-they are still only rarely included in climate impact assessments
      and the links between the hydrological system and climate are rarely acknowledged
      in studies of ecosystem services. Nevertheless, because water is essential not
      only for its direct uses but also for the indirect functions that it serves
      (including food production, fisheries and industry), it is vital that these
      connected systems are studied. Building on the examples above, we highlight
      recent research showing that assessment of these trade-offs is particularly
      complex in wetland areas, especially in situations where these trade-offs play to
      the advantage of different communities. 

PMID- 24080622
TI  - A cost-effectiveness analysis of water security and water quality: impacts of
      climate and land-use change on the River Thames system.
AB  - The catchment of the River Thames, the principal river system in southern
      England, provides the main water supply for London but is highly vulnerable to
      changes in climate, land use and population. The river is eutrophic with
      significant algal blooms with phosphorus assumed to be the primary chemical
      indicator of ecosystem health. In the Thames Basin, phosphorus is available from
      point sources such as wastewater treatment plants and from diffuse sources such
      as agriculture. In order to predict vulnerability to future change, the
      integrated catchments model for phosphorus (INCA-P) has been applied to the river
      basin and used to assess the cost-effectiveness of a range of mitigation and
      adaptation strategies. It is shown that scenarios of future climate and land-use
      change will exacerbate the water quality problems, but a range of mitigation
      measures can improve the situation. A cost-effectiveness study has been
      undertaken to compare the economic benefits of each mitigation measure and to
      assess the phosphorus reductions achieved. The most effective strategy is to
      reduce fertilizer use by 20% together with the treatment of effluent to a high
      standard. Such measures will reduce the instream phosphorus concentrations to
      close to the EU Water Framework Directive target for the Thames. 

PMID- 24080623
TI  - Catalysing sustainable water security: role of science, innovation and
      partnerships.

PMID- 24080624
TI  - Managing hydroclimatic risks in federal rivers: a diagnostic assessment.
AB  - Hydroclimatic risks and adaptive capacity are not distributed evenly in large
      river basins of federal countries, where authority is divided across national and
      territorial governments. Transboundary river basins are a major test of federal
      systems of governance because key management roles exist at all levels. This
      paper examines the evolution and design of interstate water allocation
      institutions in semi-arid federal rivers prone to drought extremes, climatic
      variability and intensified competition for scarce water. We conceptualize,
      categorize and compare federal rivers as social-ecological systems to analyse the
      relationship between governance arrangements and hydroclimatic risks. A
      diagnostic approach is used to map over 300 federal rivers and classify the
      hydroclimatic risks of three semi-arid federal rivers with a long history of
      interstate allocation tensions: the Colorado River (USA/Mexico), Ebro River
      (Spain) and Murray-Darling River (Australia). Case studies review the evolution
      and design of water allocation institutions. Three institutional design trends
      have emerged: adoption of proportional interstate allocation rules; emergence of
      multi-layered river basin governance arrangements for planning, conflict
      resolution and joint monitoring; and new flexibility to adjust historic
      allocation patterns. Proportional allocation rules apportion water between states
      based on a share of available water, not a fixed volume or priority. Interstate
      allocation reform efforts in the Colorado and Murray-Darling rivers indicate that
      proportional allocation rules are prevalent for upstream states, while downstream
      states seek reliable deliveries of fixed volumes to increase water security.
      River basin governance arrangements establish new venues for multilayered
      planning, monitoring and conflict resolution to balance self governance by users
      and states with basin-wide coordination. Flexibility to adjust historic
      allocation agreements, without risk of defection or costly court action, also
      provides adaptive capacity to manage climatic variability and shifting values.
      Future research should develop evidence about pathways to adaptive capacity in
      different classes of federal rivers, while acknowledging limits to
      transferability and the need for context-sensitive design. 

PMID- 24080625
TI  - Is water security necessary? An empirical analysis of the effects of climate
      hazards on national-level economic growth.
AB  - The influence of climate and the role of water security on economic growth are
      topics of growing interest. Few studies have investigated the potential role that
      climate hazards, which water security addresses, and their cumulative effects
      have on the growth prospects for a country. Owing to the relatively stationary
      spatial patterns of global climate, certain regions and countries are more prone
      to climate hazards and climate variability than others. For example, El
      Nino/Southern Oscillation patterns result in greater hydroclimatic variability in
      much of the tropics than that experienced at higher latitudes. In this study, we
      use a precipitation index that preserves the spatial and temporal variability of
      precipitation and differentiates between precipitation maxima (e.g. floods) and
      minima (e.g. droughts). The index is a more precise instrument for hydroclimate
      hazards than that used in any previous studies. A fixed effects, for year and
      country, regression model was developed to test the influence of climate
      variables on measures of economic growth and activity. The results indicate that
      precipitation extremes (i.e. floods and droughts) are the dominant climate
      influences on economic growth and that the effects are significant and negative.
      The drought index was found to be associated with a highly significant negative
      influence on gross domestic product (GDP) growth, while the flood index was
      associated with a negative influence on GDP growth and lagged effects on growth.
      The flood index was also found to have a negative effect on industrial value
      added in contemporary and lagged regressions. Temperature was found to have
      little significant effect. These results have important implications for economic
      projections of climate change impacts. Perhaps more important, the results make
      clear that hydroclimatic hazards have measurable negative impacts, and thus lack
      of water security is an impediment to growth. In addition, adaptation strategies
      should recognize the importance of managing hazards given the identification of
      precipitation extremes as the key climate influence on historical GDP growth. 

PMID- 24080626
TI  - Risks and responses to universal drinking water security.
AB  - Risks to universal drinking water security are accelerating due to rapid
      demographic, climate and economic change. Policy responses are slow, uneven and
      largely inadequate to address the nature and scale of the global challenges. The
      challenges relate both to maintaining water security in increasingly fragile
      supply systems and to accelerating reliable access to the hundreds of millions
      who remain water-insecure. A conceptual framework illustrates the relationship
      between institutional, operational and financial risks and drinking water
      security outcomes. We apply the framework to nine case studies from rural and
      urban contexts in South Asia and sub-Saharan Africa. Case studies are purposively
      selected based on established and emerging examples of political, technological
      or institutional reforms that address water security risks. We find broad
      evidence that improved information flows reduce institutional costs and promote
      stronger and more transparent operational performance to increase financial
      sustainability. However, political barriers need to be overcome in all cases
      through internal or external interventions that require often decadal time frames
      and catalytic investments. No single model exists, though there is sufficient
      evidence to demonstrate that risks to drinking water security can be reduced even
      in the most difficult and challenging contexts. 

PMID- 24080627
TI  - The role of technology in achieving water security.

PMID- 24080628
TI  - Domestic water and sanitation as water security: monitoring, concepts and
      strategy.
AB  - Domestic water and sanitation provide examples of a situation where long-term,
      target-driven efforts have been launched with the objective of reducing the
      proportion of people who are water-insecure, most recently through the millennium
      development goals (MDGs) framework. Impacts of these efforts have been monitored
      by an increasingly evidence-based system, and plans for the next period of
      international policy, which are likely to aim at universal coverage with basic
      water and sanitation, are being currently developed. As distinct from many other
      domains to which the concept of water security is applied, domestic or personal
      water security requires a perspective that incorporates the reciprocal notions of
      provision and risk, as the current status of domestic water and sanitation
      security is dominated by deficiency This paper reviews the interaction of science
      and technology with policies, practice and monitoring, and explores how far
      domestic water can helpfully fit into the proposed concept of water security, how
      that is best defined, and how far the human right to water affects the situation.
      It is considered that they fit well together in terms both of practical planning
      of targets and indicators and as a conceptual framework to help development. The
      focus needs to be broad, to extend beyond households, to emphasize maintenance as
      well as construction and to increase equity of access. International and
      subnational monitoring need to interact, and monitoring results need to be
      meaningful to service providers as well as users. 

PMID- 24080629
TI  - The governance dimensions of water security: a review.
AB  - Water governance is critical to water security, and to the long-term
      sustainability of the Earth's freshwater systems. This review examines recent
      debates regarding the governance dimensions of water security, including adaptive
      governance, polycentric governance, social learning and multi-level governance.
      The analysis emphasizes the political and institutional dimensions of water
      governance, and explores the relevance of social power-an overlooked yet
      important aspect of the water security debate. In addition, the review explores
      the intersection and potential synergies between water governance perspectives
      and risk-based approaches to water security, and offers critiques and suggestions
      for further research questions and agendas. 

PMID- 24080630
TI  - Preface.

PMID- 24080631
TI  - Influence of the CCR-5/MIP-1 alpha axis in the pathogenesis of Rocio virus
      encephalitis in a mouse model.
AB  - Rocio virus (ROCV) caused an outbreak of human encephalitis during the 1970s in
      Brazil and its immunopathogenesis remains poorly understood. CC-chemokine
      receptor 5 (CCR5) is a chemokine receptor that binds to macrophage inflammatory
      protein (MIP-1 alpha). Both molecules are associated with inflammatory cells
      migration during infections. In this study, we demonstrated the importance of the
      CCR5 and MIP-1 alpha, in the outcome of viral encephalitis of ROCV-infected mice.
      CCR5 and MIP-1 alpha knockout mice survived longer than wild-type (WT) ROCV
      infected animals. In addition, knockout mice had reduced inflammation in the
      brain. Assessment of brain viral load showed mice virus detection five days post
      infection in wild-type and CCR5-/- mice, while MIP-1 alpha-/- mice had lower
      viral loads seven days post-infection. Knockout mice required a higher lethal
      dose than wild-type mice as well. The CCR5/MIP-1 alpha axis may contribute to
      migration of infected cells to the brain and consequently affect the pathogenesis
      during ROCV infection.

PMID- 24080632
TI  - Simultaneous detection of seven sexually transmitted agents in human
      immunodeficiency virus-infected Brazilian women by multiplex polymerase chain
      reaction.
AB  - We determined the prevalence of seven clinically important pathogens that cause
      sexually transmitted infections (STIs) (Chlamydia trachomatis, Neisseria
      gonorrhoeae, Mycoplasma genitalium, Trichomonas vaginalis, herpes simplex virus 1
      [HSV-1], HSV-2, and Treponema pallidum), by using a multiplex polymerase chain
      reaction (M-PCR) in samples from Brazilian woman infected with human
      immunodeficiency virus 1 (HIV-1) and uninfected Brazilian women (controls). The M
      PCR assay identified all STIs tested for and surprisingly, occurred association
      between the control and STIs. This association was probably caused by excellent
      HIV infection control and regular monitoring in these women established by public
      health strategies in Brazil to combat HIV/acquired immunodeficiency syndrome.
      Studies using this M-PCR in different populations may help to better elucidate
      the roles of STIs in several conditions.

PMID- 24080633
TI  - Hepatic mass caused by Fasciola hepatica: a tricky differential diagnosis.
AB  - Fascioliasis is a zoonotic infestation caused by the trematode fasciola hepatica.
      It presents a wide spectrum of clinical pictures ranging from fever and
      eosinophilia to ambiguous gastrointestinal symptoms in the acute phase. However,
      it may often be overlooked, especially in the acute phase, because of uncertain
      symptoms. Fasciola hepatica can have an initial presentation similar to the
      presentation of malignancy. Here, we report a case of a hepatic mass caused by
      fasciola hepatica.

PMID- 24080634
TI  - Coincident tick infestations in the nostrils of wild chimpanzees and a human in
      Uganda.
AB  - Ticks in the nostrils of humans visiting equatorial African forests have been
      reported sporadically for decades, but their taxonomy and natural history have
      remained obscure. We report human infestation with a nostril tick in Kibale
      National Park, Uganda, coincident with infestation of chimpanzees in the same
      location with nostril ticks, as shown by high-resolution digital photography. The
      human-derived nostril tick was identified morphologically and genetically as a
      nymph of the genus Amblyomma, but the mitochondrial 12S ribosomal RNA or the
      nuclear intergenic transcribed spacer 2 DNA sequences of the specimen were not
      represented in GenBank. These ticks may represent a previously uncharacterized
      species that is adapted to infesting chimpanzee nostrils as a defense against
      grooming. Ticks that feed upon apes and humans may facilitate cross-species
      transmission of pathogens, and the risk of exposure is likely elevated for
      persons who frequent ape habitats.

PMID- 24080635
TI  - Marked decline in malaria prevalence among pregnant women and their offspring
      from 1996 to 2010 on the south Kenyan Coast.
AB  - Expanded malaria control in Kenya since the early 2000s has resulted in marked
      reduction in hospital admissions for malaria; however, no studies have reported
      changes in malaria infection rates in the same population over this period.
      Randomly selected archived blood samples from four cohorts of pregnant women and
      their children from 1996 to 2010 in Kwale District, Coast Province, Kenya, were
      examined for Plasmodium falciparum (Pf), P. malariae, P. ovale, and Plasmodium
      vivax by quantitative polymerase chain reaction (PCR) and microscopy. Maternal
      delivery Pf prevalence by PCR declined from 40% in 2000-2005 to 1% in 2009-2010,
      concordant with increased bed net and malaria chemoprophylaxis use. Individual
      risk of Pf infection in children from birth to 3 years in serial longitudinal
      cohort studies declined from almost 100% in 1996-1999 to 15% in 2006-2010.
      Declines in P. malariae and P. ovale infections rates were also observed. These
      results show a profound reduction in malaria transmission in coastal Kenya.

PMID- 24080636
TI  - Validation of ELISA for quantitation of artemisinin-based antimalarial drugs.
AB  - The circulation of counterfeit or substandard artemisinins (ARTs) in malaria
      endemic areas poses a serious threat to the long-term use of these drugs. Here,
      we validated an indirect competitive enzyme-linked immunosorbent assay (icELISA)
      for quantification of ARTs and found that 50% of inhibitory concentrations of
      dihydroartemisinin, artemether, and artesunate were 8.1, 207.0, and 4.7 ng/mL,
      respectively. We compared the icELISA with high-performance liquid chromatography
      (HPLC) for quantifying ART and its derivatives in 22 convenience samples of
      commercial antimalarial drugs. Paired t tests showed a borderline significant
      difference between the two methods (mean = 0.03, 95% confidence interval [CI]
      0.00-0.07, P = 0.074) and the icELISA results were more variable than those of
      the HPLC analysis (P < 0.001), suggesting that further improvement is needed to
      enhance the performance of the icELISA. Our results showed that the icELISA has
      the potential to be improved for quality assurance of ARTs at the point of care
      in endemic settings.

PMID- 24080637
TI  - Urban leptospirosis in Africa: a cross-sectional survey of Leptospira infection
      in rodents in the Kibera urban settlement, Nairobi, Kenya.
AB  - Leptospirosis is a widespread but under-reported cause of morbidity and
      mortality. Global re-emergence of leptospirosis has been associated with the
      growth of informal urban settlements in which rodents are thought to be important
      reservoir hosts. Understanding the multi-host epidemiology of leptospirosis is
      essential to control and prevent disease. A cross-sectional survey of rodents in
      the Kibera settlement in Nairobi, Kenya was conducted in September-October 2008
      to demonstrate the presence of pathogenic leptospires. A real-time quantitative
      polymerase chain reaction showed that 41 (18.3%) of 224 rodents carried
      pathogenic leptospires in their kidneys, and sequence data identified Leptospira
      interrogans and L. kirschneri in this population. Rodents of the genus Mus (37 of
      185) were significantly more likely to be positive than those of the genus Rattus
      (4 of 39; odds ratio = 15.03). Questionnaire data showed frequent contact between
      humans and rodents in Kibera. This study emphasizes the need to quantify the
      public health impacts of this neglected disease at this and other urban sites in
      Africa.

PMID- 24080638
TI  - Handwashing before food preparation and child feeding: a missed opportunity for
      hygiene promotion.
AB  - Enteric diseases are often caused by poor hygiene and can contribute to stunting.
      From 50 randomly selected villages in Bangladesh, we collected quantitative and
      qualitative data on handwashing linked to child feeding to integrate handwashing
      promotion into a young child complementary feeding program. Most participants
      stated that the community knew the importance of handwashing with soap before
      food preparation and feeding a child, but had not developed the habit. We
      observed no handwashing with soap at these key times; sometimes hands were rinsed
      with water only. Most participants cited the unavailability of soap and water
      near the cooking place as a barrier to handwashing before food preparation. Most
      caregivers ranked nurturing messages as the best motivator to encourage
      handwashing with soap. An integrated intervention should include having soap and
      water available near the food preparation area and should use nurturing themes to
      encourage habitual handwashing with soap.

PMID- 24080639
TI  - Contamination of PDMS microchannels by lithographic molds.
AB  - By use of synchrotron X-ray fluorescence and Rutherford backscattering
      spectrometry, we show the SU-8 soft lithographic process contaminates PDMS.
      Residues of the antimony containing photoinitiator are transferred from the
      master mold to the surface of PDMS, uncontrollably intensifying the surface
      potential, leading to electroosmotic flow variability in PDMS microfluidic
      devices. 

PMID- 24080641
TI  - Treatment of BRAF-mutant melanoma: the role of vemurafenib and other therapies.
AB  - The discovery of activating BRAF mutations in melanomas has led to the
      investigation of small molecular inhibitors targeting BRAF mutation and MEK, a
      downstream protein within the mitogen-activated protein kinase (MAPK) pathway.
      This article reviews the role of mutant BRAF in melanoma and summarizes the
      results of clinical trials evaluating inhibitors of BRAF and MEK in BRAF-mutant
      melanoma. We further describe recent findings on the mechanisms of resistance to
      BRAF inhibitors and discuss ongoing efforts to combine BRAF inhibitors with other
      targeted agents. Finally, we review the results of immunotherapy in BRAF-mutant
      melanoma and address the current status of efforts to either combine or determine
      the optimal sequence of these two distinct treatment approaches. Although the
      recent advances in melanoma therapy have been dramatic, greater understanding of
      melanoma biology coupled with the successful development of several new
      treatments and combination regimens will further improve patient outcomes in the
      future.

PMID- 24080640
TI  - Cholesteryl ester transfer protein polymorphisms, statin use, and their impact on
      cholesterol levels and cardiovascular events.
AB  - The association of nonfunctional variants of the cholesteryl ester transfer
      protein (CETP) with efficacy of statins has been a subject of debate. We
      evaluated whether three functional CETP variants influence statin efficacy. The
      effect of CETP genotype on achieved levels of high-density lipoprotein
      cholesterol (HDLc), low-density lipoprotein cholesterol (LDLc), and total
      cholesterol during statin treatment was estimated by meta-analysis of the linear
      regression outcomes of three studies (11,021 individuals). The effect of these
      single-nucleotide polymorphisms (SNPs) on statin response in protecting against
      myocardial infarction (MI) was estimated by meta-analysis of statin * SNP
      interaction terms from logistic regression in five studies (16,570 individuals).
      The enhancer SNP rs3764261 significantly increased HDLc by 0.02 mmol/l per T
      allele (P = 6 * 10(-5)) and reduced protection against MI by statins (interaction
      odds ratio (OR) = 1.19 per T allele; P = 0.04). Focusing on functional CETP
      variants, we showed that in carriers of the rs3764261 T variant, HDLc increased
      more during statin treatment, and protection against MI by statins appeared to be
      reduced as compared with those in noncarriers. 

PMID- 24080642
TI  - Parathyroidectomy reduces intradialytic hypotension in hemodialysis patients with
      secondary hyperparathyroidism.
AB  - BACKGROUND: Secondary hyperparathyroidism is associated with vascular
      calcification and arterial stiffness in patients with end-stage renal disease.
      The aim of this study was to analyze the frequency of intradialytic hypotension
      (IDH) and cardiovascular function before and after parathyroidectomy (PTX) in
      maintenance hemodialysis patients. METHODS: We compared predialytic and
      intradialytic blood pressure, left and right ventricular ejection fraction (LVEF
      and RVEF), and cardiothoracic ratio 1 month before PTX, and 6 and 12 months after
      PTX. IDH was defined as a decrease in systolic blood pressure >= 20 mmHg or a
      decrease in mean arterial pressure >= 10 mmHg. RESULTS: At the time of PTX, the
      mean age of the patients was 57.4 +/- 12.0 years, and the mean dialysis vintage
      was 12.2 +/- 5.8 years. At baseline, 6 months, and 12 months after PTX, the
      average numbers of sessions disturbed by IDH during 13 dialysis sessions (1
      month) were 6.4, 3.9 (p < 0.016 vs. baseline), and 4.0 sessions (p < 0.037 vs.
      baseline, p = 0.801 vs. 6 months), respectively. LVEF and RVEF were improved
      significantly after PTX. Furthermore, volume status was also improved, as
      evidenced by the significantly greater ultrafiltration volume and reduced
      cardiothoracic ratio. CONCLUSIONS: Hemodialysis patients with severe secondary
      hyperparathyroidism are more likely to achieve normotensive and euvolemic status
      after PTX, probably through improved heart function and reduced IDH episodes.

PMID- 24080643
TI  - Evaluation of the permeability of formaldehyde and water through a permeation
      tube for the preparation of an accurate formaldehyde reference gas mixture.
AB  - A system for continuous generation and analysis of formaldehyde (HCHO) in a
      nitrogen gas mixture prepared using a permeation method was fabricated in order
      to evaluate the permeability of HCHO and water (H2O) through a permeation tube.
      Specifically, the mass balance of HCHO and H2O through a permeation tube was
      evaluated using the system. The results indicated that the mass loss in the
      permeation tube accounted for the amount of HCHO and H2O measured using a
      spectrometer. The permeability of HCHO was calculated by subtracting the mass
      loss of H2O from the permeation tube per unit of time as determined from the mass
      balance results. The calculated permeability of HCHO was 75.7 +/- 3.4 mg min(-1)
      (k = 2) for the HCHO gas mixture prepared by the permeation method using a
      permeation tube filled with paraformaldehyde that was vacuum-dried at 95  degrees
      C. The calculated permeability agreed with the permeability obtained using the
      dinitrophenylhydrazine-derivatization method (72.7 +/- 4.4 mg min(-1) (k = 2))
      within the level of uncertainty. This technique, in which the mass loss of H2O
      from the permeation tube is subtracted, can therefore provide a reference gas
      mixture with an accurate HCHO concentration using the permeation method. 

PMID- 24080644
TI  - High-dose daptomycin therapy for left-sided infective endocarditis: a prospective
      study from the international collaboration on endocarditis.
AB  - The use of daptomycin in Gram-positive left-sided infective endocarditis (IE) has
      significantly increased. The purpose of this study was to assess the influence of
      high-dose daptomycin on the outcome of left-sided IE due to Gram-positive
      pathogens. This was a prospective cohort study based on 1,112 cases from the
      International Collaboration on Endocarditis (ICE)-Plus database and the ICE
      Daptomycin Substudy database from 2008 to 2010. Among patients with left-sided IE
      due to Staphylococcus aureus, coagulase-negative staphylococci, and Enterococcus
      faecalis, we compared those treated with daptomycin (cohort A) to those treated
      with standard-of-care (SOC) antibiotics (cohort B). The primary outcome was in
      hospital mortality. Time to clearance of bacteremia, 6-month mortality, and
      adverse events (AEs) ascribable to daptomycin were also assessed. There were 29
      and 149 patients included in cohort A and cohort B, respectively. Baseline
      comorbidities did not differ between the two cohorts, except for a significantly
      higher prevalence of diabetes and previous episodes of IE among patients treated
      with daptomycin. The median daptomycin dose was 9.2 mg/kg of body weight/day. Two
      thirds of the patients treated with daptomycin had failed a previous antibiotic
      regimen. In-hospital and 6-month mortalities were similar in the two cohorts. In
      cohort A, median time to clearance of methicillin-resistant S. aureus (MRSA)
      bacteremia was 1.0 day, irrespective of daptomycin dose, representing a
      significantly faster bacteremia clearance compared to SOC (1.0 versus 5.0 days; P
      < 0.01). Regimens with higher daptomycin doses were not associated with increased
      incidence of AEs. In conclusion, higher-dose daptomycin may be an effective and
      safe alternative to SOC in the treatment of left-sided IE due to common Gram
      positive pathogens. 

PMID- 24080645
TI  - Biochemical analysis of the role of G118R-linked dolutegravir drug resistance
      substitutions in HIV-1 integrase.
AB  - Drug resistance mutations (DRMs) have been reported for all currently approved
      anti-HIV drugs, including the latest integrase strand transfer inhibitors
      (INSTIs). We previously used the new INSTI dolutegravir (DTG) to select a G118R
      integrase resistance substitution in tissue culture and also showed that
      secondary substitutions emerged at positions H51Y and E138K. Now, we have
      characterized the impact of the G118R substitution, alone or in combination with
      either H51Y or E138K, on 3' processing and integrase strand transfer activity.
      The results show that G118R primarily impacted the strand transfer step of
      integration by diminishing the ability of integrase-long terminal repeat (LTR)
      complexes to bind target DNA. The addition of H51Y and E138K to G118R partially
      restored strand transfer activity by modulating the formation of integrase-LTR
      complexes through increasing LTR DNA affinity and total DNA binding,
      respectively. This unique mechanism, in which one function of HIV integrase
      partially compensates for the defect in another function, has not been previously
      reported. The G118R substitution resulted in low-level resistance to DTG,
      raltegravir (RAL), and elvitegravir (EVG). The addition of either of H51Y or
      E138K to G118R did not enhance resistance to DTG, RAL, or EVG. Homology modeling
      provided insight into the mechanism of resistance conferred by G118R as well as
      the effects of H51Y or E138K on enzyme activity. The G118R substitution therefore
      represents a potential avenue for resistance to DTG, similar to that previously
      described for the R263K substitution. For both pathways, secondary substitutions
      can lead to either diminished integrase activity and/or increased INSTI
      susceptibility. 

PMID- 24080646
TI  - Antibiotic treatment of infections due to carbapenem-resistant
      Enterobacteriaceae: systematic evaluation of the available evidence.
AB  - We sought to evaluate the effectiveness of the antibiotic treatment administered
      for infections caused by carbapenemase-producing Enterobacteriaceae. The PubMed
      and Scopus databases were systematically searched. Articles reporting the
      clinical outcomes of patients infected with carbapenemase-producing
      Enterobacteriaceae according to the antibiotic treatment administered were
      eligible. Twenty nonrandomized studies comprising 692 patients who received
      definitive treatment were included. Almost all studies reported on Klebsiella
      spp. In 8 studies, the majority of infections were bacteremia, while pneumonia
      and urinary tract infections were the most common infections in 12 studies. In 10
      studies, the majority of patients were critically ill. There are methodological
      issues, including clinical heterogeneity, that preclude the synthesis of the
      available evidence using statistical analyses, including meta-analysis. From the
      descriptive point of view, among patients who received combination treatment,
      mortality was up to 50% for the tigecycline-gentamicin combination, up to 64% for
      tigecycline-colistin, and up to 67% for carbapenem-colistin. Among the
      monotherapy-treated patients, mortality was up to 57% for colistin and up to 80%
      for tigecycline. Certain regimens were administered to a small number of patients
      in certain studies. Three studies reporting on 194 critically ill patients with
      bacteremia showed individually significantly lower mortality in the combination
      arm than in the monotherapy arm. In the other studies, no significant difference
      in mortality was recorded between the compared groups. Combination antibiotic
      treatment may be considered the optimal option for severely ill patients with
      severe infections. However, well-designed randomized studies of specific patient
      populations are needed to further clarify this issue. 

PMID- 24080647
TI  - GRL-04810 and GRL-05010, difluoride-containing nonpeptidic HIV-1 protease
      inhibitors (PIs) that inhibit the replication of multi-PI-resistant HIV-1 in
      vitro and possess favorable lipophilicity that may allow blood-brain barrier
      penetration.
AB  - We designed, synthesized, and identified two novel nonpeptidic human
      immunodeficiency virus type 1 (HIV-1) protease inhibitors (PIs), GRL-04810 and
      GRL-05010, containing the structure-based designed privileged cyclic ether
      derived nonpeptide P2 ligand, bis-tetrahydrofuranylurethane (bis-THF), and a
      difluoride moiety, both of which are active against the laboratory strain HIV
      1LAI (50% effective concentrations [EC50s], 0.0008 and 0.003 MUM, respectively)
      with minimal cytotoxicity (50% cytotoxic concentrations [CC50s], 17.5 and 37.0
      MUM, respectively, in CD4(+) MT-2 cells). The two compounds were active against
      multi-PI-resistant clinical HIV-1 variants isolated from patients who had no
      response to various antiviral regimens. GRL-04810 and GRL-05010 also blocked the
      infectivity and replication of each of the HIV-1NL4-3 variants selected by up to
      5 MUM lopinavir (EC50s, 0.03 and 0.03 MUM, respectively) and atazanavir (EC50s,
      0.02 and 0.04 MUM, respectively). Moreover, they were active against darunavir
      (DRV)-resistant variants (EC50 in 0.03 to 0.034 MUM range for GRL-04810 and 0.026
      to 0.043 MUM for GRL-05010), while DRV had EC50s between 0.02 and 0.174 MUM. GRL
      04810 had a favorable lipophilicity profile as determined with the partition (log
      P) and distribution (log D) coefficients of -0.14 and -0.29, respectively. The in
      vitro blood-brain barrier (BBB) permeability assay revealed that GRL-04810 and
      GRL-05010 may have a greater advantage in terms of crossing the BBB than the
      currently available PIs, with apparent penetration indexes of 47.8 * 10(-6) and
      61.8 * 10(-6) cm/s, respectively. The present data demonstrate that GRL-04810 and
      GRL-05010 exert efficient activity against a wide spectrum of HIV-1 variants in
      vitro and suggest that two fluorine atoms added to their bis-THF moieties may
      well enhance their penetration across the BBB. 

PMID- 24080648
TI  - 4-(1H)-Quinolones and 1,2,3,4-Tetrahydroacridin-9(10H)-ones prevent the
      transmission of Plasmodium falciparum to Anopheles freeborni.
AB  - Malaria kills approximately 1 million people a year, mainly in sub-Saharan
      Africa. Essential steps in the life cycle of the parasite are the development of
      gametocytes, as well as the formation of oocysts and sporozoites, in the
      Anopheles mosquito vector. Preventing transmission of malaria through the
      mosquito is necessary for the control of the disease; nevertheless, the vast
      majority of drugs in use act primarily against the blood stages. The study
      described herein focuses on the assessment of the transmission-blocking
      activities of potent antierythrocytic stage agents derived from the 4(1H)
      quinolone scaffold. In particular, three 3-alkyl- or 3-phenyl-4(1H)-quinolones
      (P4Qs), one 7-(2-phenoxyethoxy)-4(1H)-quinolone (PEQ), and one 1,2,3,4
      tetrahydroacridin-9(10H)-one (THA) were assessed for their transmission-blocking
      activity against the mosquito stages of the human malaria parasite (Plasmodium
      falciparum) and the rodent parasite (P. berghei). Results showed that all of the
      experimental compounds reduced or prevented the exflagellation of male
      gametocytes and, more importantly, prevented parasite transmission to the
      mosquito vector. Additionally, treatment with ICI 56,780 reduced the number of
      sporozoites that reached the Anopheles salivary glands. These findings suggest
      that 4(1H)-quinolones, which have activity against the blood stages, can also
      prevent the transmission of Plasmodium to the mosquito and, hence, are
      potentially important drug candidates to eradicate malaria. 

PMID- 24080650
TI  - One-month transplacental pharmacokinetics of raltegravir in a premature newborn
      after short-course treatment of the HIV-1-infected mother.
AB  - We describe the pharmacokinetics of raltegravir of a preterm newborn after short
      course treatment of the mother tested HIV + the day of delivery. At age 1 month,
      the circulating concentration of raltegravir in the newborn was 29 ng/ml (the
      IC95 of RAL against HIV-1 is 15 ng/ml). Raltegravir should therefore be
      considered a potential transplacental postexposure prophylaxis for HIV-1 and an
      alternative to the use of boosted lopinavir in this context. 

PMID- 24080649
TI  - Safety, tolerability, and pharmacokinetics of ribavirin in hepatitis C virus
      infected patients with various degrees of renal impairment.
AB  - Ribavirin (RBV) is an integral part of standard-of-care hepatitis C virus (HCV)
      treatments and many future regimens under investigation. The pharmacokinetics
      (PK), safety, and tolerability of RBV in chronically HCV-infected patients with
      renal impairment are not well defined and were the focus of an open-label PK
      study in HCV-infected patients receiving RBV plus pegylated interferon. Serial
      RBV plasma samples were collected over 12 h on day 1 of weeks 1 and 12 from
      patients with moderate renal impairment (creatinine clearance [CLCR], 30 to 50
      ml/min; RBV, 600 mg daily), severe renal impairment (CLCR, <30 ml/min; RBV, 400
      mg daily), end-stage renal disease (ESRD) (RBV, 200 mg daily), or normal renal
      function (CLCR, >80 ml/min; RBV, 800 to 1,200 mg daily). Of the 44 patients, 9
      had moderately impaired renal function, 10 had severely impaired renal function,
      13 had ESRD, and 12 had normal renal function. The RBV dose was reduced because
      of adverse events (AEs) in 71% and 53% of severe and moderate renal impairment
      groups, respectively. Despite this modification, patients with moderate and
      severe impairment had 12-hour (area under the concentration-time curve from 0 to
      12 h [AUC0-12]) values 36% (38,452 ng . h/ml) and 25% (35,101 ng . h/ml) higher,
      respectively, than those with normal renal function (28,192 ng . h/ml). Patients
      with ESRD tolerated a 200-mg daily dose, and AUC0-12 was 20% lower (22,629 ng .
      h/ml) than in patients with normal renal function. PK modeling and simulation
      (M&S) indicated that doses of 200 mg or 400 mg alternating daily for patients
      with moderate renal impairment and 200 mg daily for patients with severe renal
      impairment were the most appropriate dose regimens in these patients. 

PMID- 24080651
TI  - Daptomycin activity against uncommonly isolated streptococcal and other gram
      positive species groups.
AB  - A total of 1,356 clinical isolates were tested against daptomycin by broth
      microdilution methods. Daptomycin was active against seven groups of viridans
      group streptococci (MIC50 and MIC90 values ranging from <=0.06 and <=0.06 MUg/ml
      [Streptococcus bovis and Streptococcus dysgalactiae] to 0.5 and 1 MUg/ml
      [Streptococcus mitis, Streptococcus oralis, and Streptococcus parasanguinis],
      respectively), beta-hemolytic streptococci serogroups C, F, and G (MIC50 and
      MIC90, <=0.06 to 0.25 and 0.12 to 0.25 MUg/ml, respectively), Corynebacterium
      spp. (MIC50 and MIC90, <=0.06 and 0.12 MUg/ml, respectively), and Micrococcus
      spp. (MIC50 and MIC90, <=0.06 and 0.25 MUg/ml, respectively). Listeria
      monocytogenes exhibited higher daptomycin MICs (MIC50 and MIC90, 2 and 4 MUg/ml,
      respectively) than other tested organisms. 

PMID- 24080652
TI  - Emergence of Staphylococcus aureus carrying multiple drug resistance genes on a
      plasmid encoding exfoliative toxin B.
AB  - We report the complete nucleotide sequence and analysis of pETBTY825, a
      Staphylococcus aureus TY825 plasmid encoding exfoliative toxin B (ETB). S. aureus
      TY825 is a clinical isolate obtained from an impetigo patient in 2002. The size
      of pETBTY825, 60.6 kbp, was unexpectedly larger than that of the archetype
      pETBTY4 (~30 kbp). Genomic comparison of the plasmids shows that pETBTY825 has
      the archetype pETBTY4 as the backbone and has a single large extra DNA region of
      22.4 kbp. The extra DNA region contains genes for resistance to aminoglycoside
      [aac(6')/aph(2")], macrolide (msrA), and penicillin (blaZ). A plasmid deletion
      experiment indicated that these three resistance elements were functionally
      active. We retrospectively examined the resistance profile of the clinical ETB
      producing S. aureus strains isolated in 1977 to 2007 using a MIC determination
      with gentamicin (GM), arbekacin (ABK), and erythromycin (EM) and by PCR analyses
      for aac(6')/aph(2") and msrA using purified plasmid preparations. The ETB
      producing S. aureus strains began to display high resistance to GM, which was
      parallel with the detection of aac(6')/aph(2") and mecA, after 1990. Conversely,
      there was no significant change in the ABK MIC during the testing period,
      although it had a tendency to slightly increase. After 2001, isolates resistant
      to EM significantly increased; however, msrA was hardly detected in ETB-producing
      S. aureus strains, and only five isolates were positive for both aac(6')/aph(2")
      and msrA. In this study, we report the emergence of a fusion plasmid carrying the
      toxin gene etb and drug resistance genes. Prevalence of the pETBTY825 carrier may
      further increase the clinical threat, since ETB-producing S. aureus is closely
      related to more severe impetigo or staphylococcal scalded-skin syndrome (SSSS),
      which requires a general antimicrobial treatment. 

PMID- 24080653
TI  - A novel investigational Fc-modified humanized monoclonal antibody, motavizumab
      YTE, has an extended half-life in healthy adults.
AB  - The study objective was to evaluate the pharmacokinetics (PK), antidrug antibody
      (ADA), and safety of motavizumab-YTE (motavizumab with amino acid substitutions
      M252Y/S254T/T256E [YTE]), an Fc-modified anti-respiratory syncytial virus (RSV)
      monoclonal antibody. Healthy adults (n = 31) were randomized to receive a single
      intravenous (i.v.) dose of motavizumab-YTE or motavizumab (0.3, 3, 15, or 30
      mg/kg) and followed for 240 days. Clearance of motavizumab-YTE was significantly
      lower (71% to 86%) and the half-life (t1/2) was 2- to 4-fold longer than with
      motavizumab. However, similar peak concentrations and volume-of-distribution
      values, indicative of similar distribution properties, were seen at all dose
      levels. The sustained serum concentrations of motavizumab-YTE were fully
      functional, as shown by RSV neutralizing activity that persisted for 240 days
      with motavizumab-YTE versus 90 days postdose for motavizumab. Safety and
      incidence of ADA were comparable between groups. In this first study of an Fc
      modified monoclonal antibody in humans, motavizumab-YTE was well tolerated and
      exhibited an extended half-life of up to 100 days. (This study has been
      registered at ClinicalTrials.gov under registration no. NCT00578682.). 

PMID- 24080654
TI  - Antibiotic-induced autoactivation of IS256 in Staphylococcus aureus.
AB  - The 3' end of rsbU, encoding the positive regulator of the stress factor sigma B,
      was identified as a hot spot for spontaneous IS256 insertion in Staphylococcus
      aureus SA137/93G. Interestingly, subinhibitory concentrations of chloramphenicol
      in combination with heat stress, as well as linezolid and spectinomycin at
      physiological temperatures, selected for such rsbU::IS256 insertion mutants. In
      consequence of the inactivation of rsbU, the IS256 transposition frequency was
      increased 4-fold in S. aureus HG001. 

PMID- 24080656
TI  - High prevalence of extended-spectrum-cephalosporin-resistant enterobacteriaceae
      in poultry meat in Switzerland: emergence of CMY-2- and VEB-6-possessing Proteus
      mirabilis.

PMID- 24080655
TI  - Genotypic analysis of the V3 region of HIV from virologic nonresponders to
      maraviroc-containing regimens reveals distinct patterns of failure.
AB  - Changes in HIV tropism from R5 to non-R5 or development of drug resistance is
      often associated with virologic failure in patients treated with maraviroc, a
      CCR5 antagonist. We sought to examine changes in HIV envelope sequences and
      inferred tropism in patients who did not respond to maraviroc-based regimens. We
      selected 181 patients who experienced early virologic failure on maraviroc
      containing therapy in the MOTIVATE trials. All patients had R5 HIV by the
      original Trofile assay before entry. We used population-based sequencing methods
      and the geno2pheno algorithm to examine changes in tropism and V3 sequences at
      the time of failure. Using deep sequencing, we assessed whether V3 sequences
      observed at failure emerged from preexisting subpopulations. From population
      genotyping data at failure, 90 patients had R5 results, and 91 had non-R5
      results. Of the latter group, the geno2pheno false-positive rate (FPR) value fell
      from a median of 20 at screening to 1.1 at failure. By deep sequencing, the
      median percentage of non-R5 variants in these patients rose from 1.4% to 99.5%
      after a median of 4 weeks on maraviroc. In 70% of cases, deep sequencing could
      detect a pretreatment CXCR4-using subpopulation, which emerged at failure.
      Overall, there were two distinct patterns of failure of maraviroc. Patients
      failing with R5 generally had few V3 substitutions and low non-R5 prevalence by
      deep sequencing. Patients with non-R5 HIV who were failing developed very-high
      prevalence non-R5 HIV (median, 99%) and had very low geno2pheno values. 

PMID- 24080657
TI  - IreB, a Ser/Thr kinase substrate, influences antimicrobial resistance in
      Enterococcus faecalis.
AB  - Enterococcus faecalis is a Gram-positive bacterium that is a major cause of
      hospital-acquired infections, in part due to its intrinsic resistance to
      cephalosporins. The mechanism that confers intrinsic cephalosporin resistance in
      enterococci remains incompletely defined. Previously, we have shown that the
      Ser/Thr protein kinase and phosphatase pair IreK and IreP act antagonistically to
      regulate cephalosporin resistance in E. faecalis. We hypothesize that IreK senses
      antibiotic-induced cell wall damage and activates a signaling pathway leading to
      antibiotic resistance. However, the factors downstream of IreK have not yet been
      identified. To discover such factors, suppressor mutations that restored
      resistance to a DeltaireK kinase mutant were identified. Mutations were found in
      IreB, a highly conserved gene of unknown function that is widespread among low-GC
      Gram-positive bacteria. We show that IreB plays a negative regulatory role in
      cephalosporin resistance and is an endogenous substrate of both IreK and IreP.
      IreB is phosphorylated on conserved threonine residues, and mutations at these
      sites impair cephalosporin resistance. Our results are consistent with a model in
      which the activity of IreB is modulated by IreK-dependent phosphorylation in a
      signaling pathway required for cephalosporin resistance and begin to shed light
      on the function of this previously uncharacterized protein. 

PMID- 24080659
TI  - BMS-986001, an HIV nucleoside reverse transcriptase inhibitor, does not degrade
      mitochondrial DNA in long-term primary cultures of cells isolated from human
      kidney, muscle, and adipose tissue.
AB  - Nucleoside/nucleotide reverse transcriptase inhibitors (NRTIs) remain the
      cornerstone of HIV treatment; however, they are associated with toxicities
      attributed in part to inhibition of mitochondrial DNA (mtDNA) polymerase gamma.
      In this study, we compared the in vitro toxicity profiles of structurally similar
      NRTIs (BMS-986001 to stavudine and tenofovir to adefovir) that differ by the
      presence of an acetylene or methyl group, respectively. Primary cultures of human
      renal proximal tubule epithelium, skeletal muscle myotubes, and differentiated
      adipocytes were exposed to the NRTIs at the maximum concentration (Cmax) reported
      for the clinically approved dose (investigational dose for BMS-986001, 600 mg)
      and a high equimolar concentration (200 MUM) for 19 days. After 19 days, BMS
      986001 did not significantly decrease mtDNA or cell protein at either
      concentration in any cell line. In contrast, stavudine significantly decreased
      mtDNA in all cultures (1.5- to 2.5-fold) (except at Cmax in renal cells) and cell
      protein in renal cells (1.4- to 2.4-fold). By day 19, at 200 MUM, tenofovir
      significantly reduced mtDNA in adipocytes (1.9-fold) and adefovir significantly
      decreased mtDNA in all cultures (3.7- to 10.2-fold); however, no significant
      reduction in mtDNA was observed at Cmax in any cell line. Adefovir also
      significantly reduced cell protein at both concentrations in renal cells (2.2- to
      2.8-fold) and at 200 MUM in muscle cells (2.0-fold). In conclusion, BMS-986001
      and tenofovir were considerably less cytotoxic than their respective structural
      analogs, demonstrating that small structural differences can contribute to
      significant differences in toxicity. 

PMID- 24080658
TI  - Impact of lipopolysaccharide-induced inflammation on the disposition of the
      aminocephalosporin cefadroxil.
AB  - The purpose of this study was to determine if the disposition of cefadroxil, an
      alpha-amino-containing beta-lactam antibiotic, changes during lipopolysaccharide
      (LPS)-induced acute inflammation. Six hours after LPS or saline treatment, mice
      received 1 nmol/g cefadroxil intravenously along with inulin for glomerular
      filtration rate (GFR) determination. Serial blood samples, along with tissue and
      urine samples, were collected at predetermined time points. In order to determine
      inflammation-induced changes in GFR, renal tubular secretion, and reabsorption,
      it was necessary to coadminister 70 mg/kg probenecid. Changes in the expression
      of the mRNA of transporters involved in cefadroxil disposition in the kidneys and
      choroid plexus were also investigated 6 h after LPS treatment. The results
      demonstrated marked increases in blood, cerebrospinal fluid, and tissue
      cefadroxil concentrations with LPS treatment. Tissue-to-blood concentration
      ratios were decreased by 4.6-fold in the choroid plexus and by 2.5-fold in the
      kidneys during LPS-induced inflammation. Renal, but not choroid plexus, mRNA
      expression of peptide transporter 2, organic-anion transporter 1 (OAT1), OAT3,
      and multidrug resistance-associated protein 4 was mildly reduced in LPS-treated
      mice. The renal clearance of cefadroxil was substantially decreased by LPS
      treatment (3-fold). GFR was also reduced by 3-fold in LPS-treated mice, but no
      significant differences in the fractional reabsorption of cefadroxil and renal
      secretion once normalized by GFR were observed. These findings demonstrated that
      LPS-induced inflammation has a dramatic effect on the renal excretion of
      cefadroxil. It appears that changes in transporter expression played a minor role
      during LPS treatment but that renal dysfunction, associated with GFR reduction,
      was responsible for the substantial increase in plasma cefadroxil concentration
      time profiles. 

PMID- 24080660
TI  - Cell culture-selected substitutions in influenza A(H3N2) neuraminidase affect
      drug susceptibility assessment.
AB  - Assessment of drug susceptibility has become an integral part of influenza virus
      surveillance. In this study, we describe the drug resistance profile of influenza
      A(H3N2) virus, A/Mississippi/05/2011, collected from a patient treated with
      oseltamivir and detected via surveillance. An MDCK cell-grown isolate of this
      virus exhibited highly reduced inhibition by the neuraminidase (NA) inhibitors
      (NAIs) oseltamivir (8,005-fold), zanamivir (813-fold), peramivir (116-fold), and
      laninamivir (257-fold) in the NA inhibition assay. Sequence analysis of its NA
      gene revealed a known oseltamivir-resistance marker, the glutamic acid-to-valine
      substitution at position 119 (E119V), and an additional change, threonine to
      isoleucine at position 148 (T148I). Unlike E119V, T148I was not detected in the
      clinical sample but acquired during viral propagation in MDCK cells. Using
      recombinant proteins, T148I by itself was shown to cause only a 6-fold increase
      in the zanamivir 50% inhibitory concentration (IC50) and had no effect on
      inhibition by other drugs. The T148I substitution reduced NA activity by 50%,
      most likely by affecting the positioning of the 150 loop at the NA catalytic
      site. Using pyrosequencing, changes at T148 were detected in 35 (23%) of 150 MDCK
      cell-grown A(H3N2) viruses tested, which was lower than the frequency of changes
      at D151 (85%), an NA residue previously implicated in cell selection. We
      demonstrate that culturing of the A(H3N2) viruses (n = 11) at a low multiplicity
      of infection delayed the emergence of the NA variants with changes at position
      148 and/or 151, especially when conducted in MDCK-SIAT1 cells. Our findings
      highlight the current challenges in monitoring susceptibility of influenza
      A(H3N2) viruses to the NAI class of antiviral drugs. 

PMID- 24080661
TI  - Pharmacokinetics of hydroxymethylnitrofurazone, a promising new prodrug for
      Chagas' disease treatment.
AB  - Hydroxymethylnitrofurazone (NFOH) is a trypanocidal prodrug of nitrofurazone
      (NF), devoid of mutagenic toxicity. The purpose of this work was to study the
      chemical conversion of NFOH into NF in sodium acetate buffer (pH 1.2 and 7.4) and
      in human plasma and to determine preclinical pharmacokinetic parameters in rats.
      At pH 1.2, the NFOH was totally transformed into NF, the parent drug, after 48 h,
      while at pH 7.4, after the same period, the hydrolysis rate was 20%. In human
      plasma, 50% of NFOH was hydrolyzed after 24 h. In the investigation of kinetic
      disposition, the concentration of drug in serum versus time curve was used to
      calculate the pharmacokinetic parameters after a single-dose regimen. NFOH showed
      a time to maximum concentration of drug in serum (Tmax) as 1 h, suggesting faster
      absorption than NF (4 h). The most important results observed were the volume of
      distribution (V) of NFOH through the tissues, which showed a rate that is 20-fold
      higher (337.5 liters/kg of body weight) than that of NF (17.64 liters/kg), and
      the concentration of NF obtained by in vivo metabolism of NFOH, which was about
      four times lower (maximum concentration of drug in serum [Cmax] = 0.83 MUg/ml;
      area under the concentration-time curve from 0 to 12 h [AUC0-12] = 5.683 MUg/ml .
      h) than observed for administered NF (Cmax = 2.78 MUg/ml; AUC0-12 = 54.49 MUg/ml
      . h). These findings can explain the superior activity and lower toxicity of the
      prodrug NFOH in relation to its parent drug and confirm NFOH as a promising anti
      Chagas' disease drug candidate. 

PMID- 24080662
TI  - Molecular epidemiology of Escherichia coli sequence type 131 and Its H30 and H30
      Rx subclones among extended-spectrum-beta-lactamase-positive and -negative E.
      coli clinical isolates from the Chicago Region, 2007 to 2010.
AB  - We assessed Escherichia coli ST131 and its H30 and H30-Rx subclones for virulence
      genes, antimicrobial resistance, and extended-spectrum beta-lactamase (ESBL)
      type. Although both subclones were associated with ESBL production, H30-Rx
      isolates had higher resistance scores and were associated specifically with CTX-M
      15. Three virulence genes (iha, sat, and iutA) were more prevalent among H30 than
      non-H30 ST131 isolates. Thus, the H30 and H30-Rx subclones are more antimicrobial
      resistant and have virulence profiles that are distinct from those of non-H30
      ST131 isolates. 

PMID- 24080663
TI  - Pharmacokinetic interaction between maraviroc and fosamprenavir-ritonavir: an
      open-label, fixed-sequence study in healthy subjects.
AB  - This open-label, fixed-sequence, phase 1 study evaluated the pharmacokinetic
      interaction between maraviroc (MVC) and ritonavir-boosted fosamprenavir (FPV/r)
      in healthy subjects. In period 1, subjects received 300 mg of MVC twice daily
      (BID; cohort 1) or once daily (QD; cohort 2) for 5 days. In period 2, cohort 1
      subjects received 700/100 mg of FPV/r BID alone on days 1 to 10 and then FPV/r at
      700/100 mg BID plus MVC at 300 mg BID on days 11 to 20; cohort 2 subjects
      received FPV/r at 1,400/100 mg QD alone on days 1 to 10 and then FPV/r at
      1,400/100 mg QD plus MVC at 300 mg QD on days 11 to 20. Pharmacokinetic
      parameters, assessed on day 5 of period 1 and on days 10 and 20 of period 2,
      included the maximum plasma concentration (Cmax), the concentration at end of
      dosing interval (Ctau), and the area under the curve over dosing interval
      (AUCtau). Safety and tolerability were also assessed. MVC geometric mean AUCtau,
      Cmax, and Ctau were increased by 149, 52, and 374%, respectively, after BID
      dosing with FPV/r, and by 126, 45, and 80%, respectively, after QD dosing.
      Amprenavir (the active form of the prodrug fosamprenavir) and ritonavir exposures
      were decreased in the presence of MVC with amprenavir AUCtau, Cmax, and Ctau
      decreased by 34 to 36% in the presence of FPV/r plus maraviroc BID and by 15 to
      30% with FPV/r plus MVC QD both compared to FPV/r alone. The overall all
      causality adverse-event (AE) incidence rate was 96.4%; all AEs were of mild or
      moderate severity. Commonly reported treatment-related AEs (>20% of patients
      overall) included diarrhea, fatigue, abdominal discomfort, headache, and nausea.
      No serious AEs or deaths occurred. In summary, maraviroc exposure increased in
      the presence of FPV/r, whereas MVC coadministration decreased amprenavir and
      ritonavir exposures. MVC dosed at 300 mg BID with FPV/r is not recommended due to
      concerns of lower amprenavir exposures; however, no dose adjustment is warranted
      with MVC at 150 mg BID in combination with FPV/r based on the available clinical
      data. MVC plus FPV/r was generally well tolerated; no new safety signals were
      detected. 

PMID- 24080664
TI  - Protein binding of beta-lactam antibiotics in critically ill patients: can we
      successfully predict unbound concentrations?
AB  - The use of therapeutic drug monitoring (TDM) to optimize beta-lactam dosing in
      critically ill patients is growing in popularity, although there are limited data
      describing the potential impact of altered protein binding on achievement of
      target concentrations. The aim of this study was to compare the measured unbound
      concentration to the unbound concentration predicted from published protein
      binding values for seven beta-lactams using data from blood samples obtained from
      critically ill patients. From 161 eligible patients, we obtained 228 and 220
      plasma samples at the midpoint of the dosing interval and trough, respectively,
      for ceftriaxone, cefazolin, meropenem, piperacillin, ampicillin,
      benzylpenicillin, and flucloxacillin. The total and unbound beta-lactam
      concentrations were measured using validated methods. Variabilities in both
      unbound and total concentrations were marked for all antibiotics, with
      significant differences being present between measured and predicted unbound
      concentrations for ceftriaxone and for flucloxacillin at the mid-dosing interval
      (P < 0.05). The predictive performance for calculating unbound concentrations
      using published protein binding values was poor, with bias for overprediction of
      unbound concentrations for ceftriaxone (83.3%), flucloxacillin (56.8%), and
      benzylpenicillin (25%) and underprediction for meropenem (12.1%). Linear
      correlations between the measured total and unbound concentrations were observed
      for all beta-lactams (R(2) = 0.81 to 1.00; P < 0.05) except ceftriaxone and
      flucloxacillin. The percent protein binding of flucloxacillin and the plasma
      albumin concentration were also found to be linearly correlated (R(2) = 0.776; P
      < 0.01). In conclusion, significant differences between measured and predicted
      unbound drug concentrations were found only for the highly protein-bound beta
      lactams ceftriaxone and flucloxacillin. However, direct measurement of unbound
      drug in research and clinical practice is suggested for selected beta-lactams. 

PMID- 24080665
TI  - Investigation of the interactions between methadone and elvitegravir-cobicistat
      in subjects receiving chronic methadone maintenance.
AB  - Interactions between HIV and opioid dependence therapies are known to occur. We
      sought to determine if such interactions occurred between methadone and
      elvitegravir boosted with cobicistat (EVG/COBI). We performed a within-subject
      open-label pharmacokinetic and pharmacodynamic study of 11 HIV-seronegative
      subjects stabilized on at least 2 weeks of methadone. Subjects underwent baseline
      and steady-state evaluation of the effect of elvitegravir 150 mg once a day (QD)
      boosted with 150 mg QD of cobicistat (EVG/COBI) on methadone pharmacokinetic
      parameters. Safety and pharmacodynamics were monitored throughout the study.
      Compared to baseline values, the R-methadone mean area under the concentration
      time curve to the end of the dosing period (AUCtau) (5,550 versus 6,210 h .
      ng/ml) and mean maximum concentration of drug in serum (Cmax) (316 versus 337
      ng/ml) did not significantly increase in the presence of EVG/COBI. Compared to
      baseline values, the S-methadone mean AUCtau (7,040 versus 7,540 h . ng/ml) and
      mean Cmax (446 versus 452 ng/ml) did not significantly increase in the presence
      of EVG/COBI. The AUCtau, Cmax, and Ctau of elvitegravir and cobicistat did not
      significantly differ from those of historical controls. Opioid withdrawal or
      overdose was not observed among subjects in this study. The addition of EVG/COBI
      to stabilized patients receiving methadone did not affect methadone
      pharmacokinetics and pharmacodynamics. These two agents can be safely
      coadministered. 

PMID- 24080666
TI  - In vitro activity of Ozenoxacin against quinolone-susceptible and quinolone
      resistant gram-positive bacteria.
AB  - In vitro activity of ozenoxacin, a novel nonfluorinated topical (L. D. Saravolatz
      and J. Leggett, Clin. Infect. Dis. 37:1210-1215, 2003) quinolone, was compared
      with the activities of other quinolones against well-characterized quinolone
      susceptible and quinolone-resistant Gram-positive bacteria. Ozenoxacin was 3-fold
      to 321-fold more active than other quinolones. Ozenoxacin could represent a first
      in-class nonfluorinated quinolone for the topical treatment of a broad range of
      dermatological infections. 

PMID- 24080668
TI  - Inflammatory effects of autologous, genetically modified autologous, allogeneic,
      and xenogeneic mesenchymal stem cells after intra-articular injection in horses.
AB  - OBJECTIVES: To compare the clinical and inflammatory joint responses to intra
      articular injection of bone marrow-derived mesenchymal stem cells (MSC) including
      autologous, genetically modified autologous, allogeneic, or xenogeneic cells in
      horses. METHODS: Six five-year-old Thoroughbred mares had one fetlock joint
      injected with Gey's balanced salt solution as the vehicle control. Each fetlock
      joint of each horse was subsequently injected with 15 million MSC from the
      described MSC groups, and were assessed for 28 days for clinical and inflammatory
      parameters representing synovitis, joint swelling, and pain. RESULTS: There were
      not any significant differences between autologous and genetically modified
      autologous MSC for synovial fluid total nucleated cell count, total protein,
      interleukin (IL)-6, IL-10, fetlock circumference, oedema score, pain-free range
      of-motion, and soluble gene products that were detected for at least two days.
      Allogeneic and xenogeneic MSC produced a greater increase in peak of inflammation
      at 24 hours than either autologous MSC group. CLINICAL SIGNIFICANCE: Genetically
      engineered MSC can act as vehicles to deliver gene products to the joint; further
      investigation into the therapeutic potential of this cell therapy is warranted.
      Intra-articular MSC injection resulted in a moderate acute inflammatory joint
      response that was greater for allogeneic and xenogeneic MSC than autologous MSC.
      Clinical management of this response may minimize this effect.

PMID- 24080667
TI  - Repeat polymorphisms in the low-complexity regions of Plasmodium falciparum ABC
      transporters and associations with in vitro antimalarial responses.
AB  - The Plasmodium falciparum genome is rich in regions of low amino acid complexity
      which evolve with few constraints on size. To explore the extent of diversity in
      these loci, we sequenced repeat regions in pfmdr1, pfmdr5, pfmdr6, pfmrp2, and
      the antigenic locus pfmsp8 in laboratory and cultured-adapted clinical isolates.
      We further assessed associations between the repeats and parasite in vitro
      responses to 7 antimalarials to determine possible adaptive roles of these
      repeats in drug tolerance. Our results show extensive repeat variations in the
      reference and clinical isolates in all loci. We also observed a modest increase
      in dihydroartemisinin activity in parasites harboring the pfmdr1 sequence profile
      7-2-10 (reflecting the number of asparagine repeats, number of aspartate repeats,
      and number of asparagine repeats in the final series of the gene product) (P =
      0.0321) and reduced sensitivity to chloroquine, mefloquine, quinine, and
      dihydroartemisinin in those with the 7-2-11 profile (P = 0.0051, 0.0068, 0.0011,
      and 0.0052, respectively). Interestingly, we noted an inverse association between
      two drugs whereby isolates with 6 asparagine repeats encoded by pfmdr6 were
      significantly more susceptible to piperaquine than those with 8 (P = 0.0057).
      Against lumefantrine, those with 8 repeats were, however, more sensitive (P =
      0.0144). In pfmrp2, the 7-DNNNTS/NNNNTS (number of DNNNTS or NNNNTS motifs;
      underlining indicates dimorphism) repeat group was significantly associated with
      a higher lumefantrine 50% inhibitory concentration (IC50) (P = 0.008) than in
      those without. No associations were observed with pfmsp8. These results hint at
      the probable utility of some repeat conformations as markers of in vitro
      antimalarial response; hence, biochemical functional studies to ascertain their
      role in P. falciparum are required. 

PMID- 24080669
TI  - Perceptions of efficacy, expressed emotion, and the course of schizophrenia: the
      case of emotional overinvolvement.
AB  - Although it is clear that expressed emotion (EE) is associated with the course of
      schizophrenia, proposed models for this association have struggled to account for
      the relationship between the EE index of emotional overinvolvement (EOI) and
      relapse. To expand our understanding of the EOI-relapse association, we first
      attempted to replicate the finding that the EOI-relapse association is
      curvilinear among 55 Mexican-Americans with schizophrenia and their caregiving
      relatives. Second, we evaluated whether the caregivers' perception of their ill
      relative's efficacy may account for the EOI-relapse association. Our results
      comport with past findings with regard to the curvilinear nature of the EOI
      relapse association among Mexican-Americans and suggest that EOI may only seem to
      be a risk factor of relapse because of its strong association with a true risk
      factor for relapse (i.e., caregivers' perception of their ill relative's
      efficacy). 

PMID- 24080670
TI  - Unique and related predictors of major depressive disorder, posttraumatic stress
      disorder, and their comorbidity after Hurricane Katrina.
AB  - The current study examined demographic and psychosocial factors that predict
      major depressive disorder (MDD) and comorbid MDD/posttraumatic stress disorder
      (MDD/PTSD) diagnostic status after Hurricane Katrina, one of the deadliest and
      costliest hurricanes in the history of the United States. This study expanded on
      the findings published in the article by Galea, Tracy, Norris, and Coffey (J
      Trauma Stress 21:357-368, 2008), which examined the same predictors for PTSD, to
      better understand related and unique predictors of MDD, PTSD, and MDD/PTSD
      comorbidity. A total of 810 individuals representative of adult residents living
      in the 23 southernmost counties of Mississippi before Hurricane Katrina were
      interviewed. Ongoing hurricane-related stressors, low social support, and
      hurricane-related financial loss were common predictors of MDD, PTSD, and
      MDD/PTSD, whereas educational and marital status emerged as unique predictors of
      MDD. Implications for postdisaster relief efforts that address the risk for both
      MDD and PTSD are discussed. 

PMID- 24080671
TI  - Adult attention deficit hyperactivity disorder symptoms and five-factor model
      traits in a clinical sample: a structural equation modeling approach.
AB  - Relationships among attention deficit hyperactivity disorder (ADHD) symptoms and
      adult personality traits have not been examined in larger clinically diagnosed
      samples. We collected multisource ADHD symptom and self-report NEO Five-Factor
      Inventory (Costa and McCrae [Odessa, FL: Psychological Assessment Resources, Inc,
      1992) data from 117 adults with ADHD and tested symptom-trait associations using
      structural equation modeling. The final model fit the data. Inattention was
      positively associated with neuroticism and negatively associated with
      conscientiousness. On the basis of ADHD expression in adulthood, hyperactivity
      and impulsivity were estimated as separate constructs and showed differential
      relationships to extraversion and agreeableness. A significant positive
      relationship between hyperactivity and conscientiousness arose in the context of
      other pathways. ADHD symptoms are reliably associated with personality traits,
      suggesting a complex interplay across development that warrants prospective study
      into adulthood. 

PMID- 24080672
TI  - Prevalence of psychotic symptoms in those with melancholic and nonmelancholic
      depression.
AB  - The best classification of depressive disorders is still to be established. A
      melancholic subtype has a lengthy history, and recent research demonstrates its
      relevance. This study compares the prevalence of psychotic symptoms in
      nonmelancholic and melancholic depression and assesses whether there is a
      dimensional pattern in the severity of symptoms among the subtypes. Patients with
      unipolar depression were assessed for melancholic status, psychotic symptoms, and
      severity of depression. The diagnosis of melancholia was made by both Diagnostic
      and Statistical Manual of Mental Disorders, Fourth Edition, Text Revision (DSM-IV
      TR), criteria and CORE measure. The DSM criteria assigned a much higher
      percentage of patients as melancholics (67.4%) than did the CORE (24.9%).
      Prevalence of psychosis was distinctly higher in the melancholics. Symptoms
      severity was higher among the melancholics when compared with the
      nonmelancholics. The presence of psychotic symptoms was not associated with an
      increase in the intensity of depressive symptoms. Psychotic symptoms are more
      frequently associated with the melancholic subtype of depression. This suggests
      clinical contiguity between the melancholic and psychotic subtypes and the
      clinical relevance of identifying melancholia. 

PMID- 24080673
TI  - GAP-REACH: a checklist to assess comprehensive reporting of race, ethnicity, and
      culture in psychiatric publications.
AB  - Growing awareness of health and health care disparities highlights the importance
      of including information about race, ethnicity, and culture (REC) in health
      research. Reporting of REC factors in research publications, however, is
      notoriously imprecise and unsystematic. This article describes the development of
      a checklist to assess the comprehensiveness and the applicability of REC factor
      reporting in psychiatric research publications. The 16-item GAP-REACH checklist
      was developed through a rigorous process of expert consensus, empirical content
      analysis in a sample of publications (N = 1205), and interrater reliability (IRR)
      assessment (N = 30). The items assess each section in the conventional structure
      of a health research article. Data from the assessment may be considered on an
      item-by-item basis or as a total score ranging from 0% to 100%. The final
      checklist has excellent IRR (kappa = 0.91). The GAP-REACH may be used by multiple
      research stakeholders to assess the scope of REC reporting in a research article.

PMID- 24080674
TI  - Self-report and longitudinal predictors of violence in Iraq and Afghanistan war
      era veterans.
AB  - This study, using a longitudinal design, attempted to identify whether self
      reported problems with violence were empirically associated with future violent
      behavior among Iraq and Afghanistan war veterans and whether and how collateral
      informant interviews enhanced the risk assessment process. Data were gathered
      from N = 300 participants (n = 150 dyads of Iraq and Afghanistan war veterans and
      family/friends). The veterans completed baseline and follow-up interviews 3 years
      later on average, and family/friends provided collateral data on dependent
      measures at follow-up. Analyses showed that aggression toward others at follow-up
      was associated with younger age, posttraumatic stress disorder, combat exposure,
      and a history of having witnessed parental violence growing up. Self-reported
      problems controlling violence at baseline had robust statistical power in
      predicting aggression toward others at follow-up. Collateral report enhanced
      detection of dependent variables: 20% of cases positive for violence toward
      others would have been missed relying only on self-report. The results identify a
      subset of Iraq and Afghanistan war veterans at higher risk for problematic
      postdeployment adjustment and indicate that the veterans' self-report of violence
      was useful in predicting future aggression. Underreporting of violence was not
      evidenced by most veterans but could be improved upon by obtaining collateral
      information. 

PMID- 24080675
TI  - Obsessive-compulsive symptoms and characteristics in individuals with delayed
      sleep phase disorder.
AB  - Research has demonstrated a relationship between circadian disruption and severe
      obsessive-compulsive disorder (OCD). Misalignment of sleep timing/endogenous
      biological rhythms with the 24-hour light/dark cycle may result in difficulty
      dismissing intrusive thoughts, thus increasing vulnerability to disorders
      characterized by intrusive thoughts, such as OCD. Deficits in inhibition of
      intrusive thoughts are posited to play a role in OCD. The current study
      investigated whether individuals with delayed sleep phase disorder (DSPD) report
      elevated symptoms of OCD and have greater difficulty inhibiting intrusive
      thoughts than do individuals without DSPD. Community participants with and
      without DSPD completed questionnaires and performed behavioral tasks designed to
      elicit intrusive thoughts. The participants with DSPD (n = 27) had elevated OCD
      symptoms and greater rates of disorders characterized by intrusive thoughts on a
      structured interview, as compared with the participants without DSPD (n = 19).
      These results support a link between the timing of sleep and symptoms of OCD.
      Implications and future directions are discussed. 

PMID- 24080676
TI  - Motor imagery in bipolar depression with slowed movement.
AB  - We hypothesized that motor retardation in bipolar depression is mediated by
      disruption of the pre-executive stages of motor production. We used functional
      magnetic resonance imaging to investigate neural activity during motor imagery
      and motor execution to elucidate whether brain regions that mediate planning,
      preparation, and control of movement are activated differently in subjects with
      bipolar depression (n = 9) compared with healthy controls (n = 12). We found
      significant between-group differences. During motor imagery, the patients
      activated the posterior medial parietal cortex, the posterior cingulate cortex,
      the premotor cortex, the prefrontal cortex, and the frontal poles more than the
      controls did. Activation in the brain areas involved in motor selection,
      planning, and preparation was altered. In addition, limbic and prefrontal regions
      associated with self-reference and the default mode network were altered during
      motor imagery in bipolar depression with motor retardation. 

PMID- 24080677
TI  - Psychoeducation for adults with attention deficit hyperactivity disorder vs.
      cognitive behavioral group therapy: a randomized controlled pilot study.
AB  - The aim of the present study was to assess the efficacy of psychoeducation as
      compared with cognitive behavioral group therapy in adults with attention deficit
      hyperactivity disorder (ADHD) who still had significant symptoms and were in
      pharmacological treatment. This is the first study on psychoeducation in adults
      with ADHD. Thirty-two individuals were randomized to two treatment conditions: 15
      were in the psychoeducation group and 11 were in the cognitive behavioral group
      therapy. A total of 30 completed treatment, and 26 completed the follow-up
      assessments. The results indicated that both treatments were associated with
      statistically significant improvements on inattention, hyperactivity,
      impulsivity, and self-esteem. The patients in both groups showed a decrease in
      anxiety symptoms and obtained significantly lower scores in depression. Measures
      on functional impairment showed statistically significant differences on improved
      quality of life and on lower global severity as perceived in self-report and
      assessed by clinician report. Psychoeducation demonstrated to be an effective
      treatment in reducing ADHD core symptoms. 

PMID- 24080678
TI  - Assessing posttraumatic stress disorder's latent structure in elderly bereaved
      European trauma survivors: evidence for a five-factor dysphoric and anxious
      arousal model.
AB  - The three-factor structure of posttraumatic stress disorder (PTSD) specified by
      the Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, is not
      supported in the empirical literature. Two alternative four-factor models have
      received a wealth of empirical support. However, a consensus regarding which is
      superior has not been reached. A recent five-factor model has been shown to
      provide superior fit over the existing four-factor models. The present study
      investigated the fit of the five-factor model against the existing four-factor
      models and assessed the resultant factors' association with depression in a
      bereaved European trauma sample (N = 325). The participants were assessed for
      PTSD via the Harvard Trauma Questionnaire and depression via the Beck Depression
      Inventory. The five-factor model provided superior fit to the data compared with
      the existing four-factor models. In the dysphoric arousal model, depression was
      equally related to both dysphoric arousal and emotional numbing, whereas
      depression was more related to dysphoric arousal than to anxious arousal. 

PMID- 24080679
TI  - Assessing the specificity of posttraumatic stress disorder's dysphoric items
      within the dysphoria model.
AB  - The factor structure of posttraumatic stress disorder (PTSD) currently used by
      the Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition (DSM
      IV), has received limited support. A four-factor dysphoria model is widely
      supported. However, the dysphoria factor of this model has been hailed as a
      nonspecific factor of PTSD. The present study investigated the specificity of the
      dysphoria factor within the dysphoria model by conducting a confirmatory factor
      analysis while statistically controlling for the variance attributable to
      depression. The sample consisted of 429 individuals who met the diagnostic
      criteria for PTSD in the National Comorbidity Survey. The results concluded that
      there was no significant attenuation in any of the PTSD items. This finding is
      pertinent given several proposals for the removal of dysphoric items from the
      diagnostic criteria set of PTSD in the upcoming DSM-5. 

PMID- 24080680
TI  - Degree of specialisation of the surgeon influences lymph node yield after right
      sided hemicolectomy.
AB  - AIM: To investigate the degree to which specialisation or case-load of the
      surgeon is associated with the number of lymph nodes isolated from pathology
      specimens after right-sided hemicolectomy. METHOD: Data from 6 hospitals with
      well-defined catchment areas included in the Uppsala/Orebro Regional Oncology
      Centre Colon Cancer Register 1997-2006 were used to assess 821 patients
      undergoing right-sided hemicolectomy for stages I-III colon cancer. Factors
      influencing the lymph node yield were evaluated. RESULTS: A surgeon with
      colorectal accreditation and a university pathology department were both
      associated with a significantly higher proportion of patients having 12 or more
      lymph nodes isolated from surgical specimens after right-sided hemicolectomy in
      both unadjusted and multivariate analyses. Emergency surgery did not affect the
      lymph node yield. CONCLUSION: The degree of specialisation of the surgeon
      influences the number of lymph nodes isolated from specimens obtained during
      routine right-sided colon cancer surgery.

PMID- 24080683
TI  - Externalizing research through adaptive frameworks.
AB  - Adaptive approaches to collaborations between industry and academic research
      institutions can enable both parties to achieve their goals more effectively.
      Here, we discuss our experience with such approaches and suggest recommendations
      for addressing the associated management challenges.

PMID- 24080681
TI  - Molecular pharmacology and ligand docking studies reveal a single amino acid
      difference between mouse and human serotonin 5-HT2A receptors that impacts
      behavioral translation of novel 4-phenyl-2-dimethylaminotetralin ligands.
AB  - During translational studies to develop 4-phenyl-2-dimethylaminotetralin (PAT)
      compounds for neuropsychiatric disorders, the (2R,4S)-trans-(+)- and (2S,4R)
      trans-(-)-enantiomers of the analog 6-hydroxy-7-chloro-PAT (6-OH-7-Cl-PAT)
      demonstrated unusual pharmacology at serotonin (5-HT) 5-HT2 G protein-coupled
      receptors (GPCRs). The enantiomers had similar affinities (Ki) at human (h) 5
      HT2A receptors (~ 70 nM). In an in vivo mouse model of 5-HT2A receptor activation
      [(+/-)-(2,5)-dimethoxy-4-iodoamphetamine (DOI)-elicited head twitch], however, (
      )-6-OH-7-Cl-PAT was about 5-fold more potent than the (+)-enantiomer at
      attenuating the DOI-elicited response. It was discovered that (+)-6-OH-7-Cl-PAT
      (only) had ~ 40-fold-lower affinity at mouse (m) compared with h5-HT2A receptors.
      Molecular modeling and computational ligand docking studies indicated that the 6
      OH moiety of (+)- but not (-)-6-OH-7-Cl-PAT could form a hydrogen bond with
      serine residue 5.46 of the h5-HT2A receptor. The m5-HT2A as well as m5-HT2B, h5
      HT2B, m5-HT2C, and h5-HT2C receptors have alanine at position 5.46, obviating
      this interaction; (+)-6-OH-7-Cl-PAT also showed ~ 50-fold lower affinity than (-)
      6-OH-7-Cl-PAT at m5-HT2C and h5-HT2C receptors. Mutagenesis studies confirmed
      that 5-HT2A S5.46 is critical for (+)- but not (-)-6-OH-7-Cl-PAT binding, as well
      as function. The (+)-6-OH-7-Cl-PAT enantiomer showed partial agonist effects at
      h5-HT2A wild-type (WT) and m5-HT2A A5.46S point-mutated receptors but did not
      activate m5-HT2A WT and h5-HT2A S5.46A point-mutated receptors, or h5-HT2B, h5
      HT2C, and m5-HT2C receptors; (-)-6-OH-7-Cl-PAT did not activate any of the 5-HT2
      receptors. Experiments also included the (2R,4S)-trans-(+)- and (2S,4R)-trans-(-)
      enantiomers of 6-methoxy-7-chloro-PAT to validate hydrogen bonding interactions
      proposed for the corresponding 6-OH analogs. Results indicate that PAT ligand
      three-dimensional structure impacts target receptor binding and translational
      outcomes, supporting the hypothesis that GPCR ligand structure governs
      orthosteric binding pocket molecular determinants and resulting pharmacology.

PMID- 24080684
TI  - PARP inhibitors bounce back.

PMID- 24080682
TI  - Hepatic basolateral efflux contributes significantly to rosuvastatin disposition
      II: characterization of hepatic elimination by basolateral, biliary, and
      metabolic clearance pathways in rat isolated perfused liver.
AB  - Basolateral efflux clearance (CLBL) contributes significantly to rosuvastatin
      (RSV) elimination in sandwich-cultured hepatocytes (SCH). The contribution of
      CLBL to RSV hepatic elimination was determined in single-pass isolated perfused
      livers (IPLs) from wild-type (WT) and multidrug resistance-associated protein 2
      (Mrp2)-deficient (TR(-)) rats in the absence and presence of the P-glycoprotein
      and breast cancer resistance protein (Bcrp) inhibitor, elacridar (GF120918);
      clearance values were compared with SCH. RSV biliary clearance (CLBile) was
      ablated almost completely by GF120918 in TR(-) IPLs, confirming that Mrp2 and
      Bcrp primarily are responsible for RSV CLBile. RSV appearance in outflow
      perfusate was attributed primarily to CLBL, which was impaired in TR(-) IPLs.
      CLBL was ~ 6-fold greater than CLBile in the linear range in WT IPLs in the
      absence of GF120918. Recovery of unchanged RSV in liver tissue increased in TR(-)
      compared with WT (~ 25 versus 6% of the administered dose) due to impaired CLBL
      and CLBile. RSV pentanoic acid, identified by high-resolution liquid
      chromatography-tandem mass spectroscopy, comprised ~ 40% of total liver content
      and ~ 16% of the administered dose in TR(-) livers at the end of perfusion,
      compared with ~ 30 and 3% in WT livers, consistent with impaired RSV excretion
      and "shunting" to the metabolic pathway. In vitro-ex vivo extrapolation between
      WT SCH and IPLs (without GF120918) revealed that uptake clearance and CLBL were
      4.2- and 6.4-fold lower, respectively, in rat SCH compared with IPLs; CLBile
      translated almost directly (1.1-fold). The present IPL data confirmed the
      significant role of CLBL in RSV hepatic elimination, and demonstrated that both
      CLBL and CLBile influence RSV hepatic and systemic exposure.

PMID- 24080688
TI  - Deal watch: AstraZeneca bets on FibroGen's anaemia drug.

PMID- 24080689
TI  - Market watch: Upcoming market catalysts in Q4 2013.

PMID- 24080690
TI  - India's patent ecosystem - encouraging strong patents or discouraging innovation?

PMID- 24080691
TI  - Daniel Hayes. Interviewed by Asher Mullard.

PMID- 24080692
TI  - Pharmaceutical forecasting: throwing darts?

PMID- 24080693
TI  - Neurodegenerative diseases: New kinase targets for Alzheimer's disease.

PMID- 24080694
TI  - Cardiology: Bromodomain inhibition halts heart failure.

PMID- 24080699
TI  - Drug discovery for autism spectrum disorder: challenges and opportunities.
AB  - The rising rates of autism spectrum disorder (ASD) and the lack of effective
      medications to treat its core symptoms have led to an increased sense of urgency
      to identify therapies for this group of neurodevelopmental conditions. Developing
      drugs for ASD, however, has been challenging because of a limited understanding
      of its pathophysiology, difficulties in modelling the disease in vitro and in
      vivo, the heterogeneity of symptoms, and the dearth of prior experience in
      clinical development. In the past few years these challenges have been mitigated
      by considerable advances in our understanding of forms of ASD caused by single
      gene alterations, such as fragile X syndrome and tuberous sclerosis. In these
      cases we have gained insights into the pathophysiological mechanisms underlying
      these conditions. In addition, they have aided in the development of animal
      models and compounds with the potential for disease modification in clinical
      development. Moreover, genetic studies are illuminating the molecular
      pathophysiology of ASD, and new tools such as induced pluripotent stem cells
      offer novel possibilities for drug screening and disease diagnostics. Finally,
      large-scale collaborations between academia and industry are starting to address
      some of the key barriers to developing drugs for ASD. Here, we propose a
      conceptual framework for drug discovery in ASD encompassing target
      identification, drug profiling and considerations for clinical trials in this
      novel area. 

PMID- 24080701
TI  - Associated factors and psychotherapy on sleep disturbances in systemic lupus
      erythematosus.
AB  - Sleep disturbance is a common problem in systemic lupus erythematosus (SLE)
      patients. This study was performed to determine the prevalence of sleep
      disturbance in SLE, the factors that might be associated with sleep disturbance,
      and the correlation between changes in clinical parameters and sleep quality over
      time. Fifty-six female SLE patients from a total of 497 SLE patients (11.3%)
      agreed to join the study. The demographic data were recorded at baseline and the
      clinical data, the Pittsburgh Sleep Quality Index (PSQI) and other standardized
      assessment tools, disease activity index, quality of life (QoL), damage index,
      depression, anxiety and fatigue score, were assessed three times: the first visit
      was at baseline, the second time was one month later, and the third time was
      three months after the baseline. Thirty-one of these 56 patients (55.36%) were
      found to have sleep disturbances. All were females with their mean +/- SD age of
      37.5 +/- 12.3 years, and disease duration at study entry of 8.6 +/- 7.3 years.
      There was no association between sleep disturbances and demographic data, disease
      activity, clinical symptoms, the presence of autoantibodies and current steroid
      use. In multiple logistic regression analyses, only moderate to severe depression
      was the independent determinant of sleep disturbances, p = 0.036. During the
      three-month observation, with the treatment, the changing of total PSQI score
      showed a significantly positive correlation with depression, anxiety, pain and
      QoL. Sleep disturbances in Thai SLE patients were not uncommon but a correctable
      condition. Depression was strongly associated with sleep disturbances. Awareness
      of underlying depression as well as sleep disturbances in SLE patients and
      treating them properly improve QoL in SLE. 

PMID- 24080703
TI  - Endocrine disruptors: a most relevant issue for the pediatric endocrinologist.

PMID- 24080704
TI  - Subclinical macular edema as a predictor of progression to clinically significant
      macular edema in type 2 diabetes.
AB  - OBJECTIVE: To examine the relationship between subclinical diabetic macular edema
      (DME) and the development of clinically significant macular edema (CSME) in
      nonproliferative diabetic retinopathy (NPDR) in patients with type 2 diabetes.
      METHODS: A prospective, monocenter, observational study was designed to follow
      patients/eyes with type 2 diabetes and NPDR (Early Treatment Diabetic Retinopathy
      Study levels 20 and 35) with no prior laser treatment for 2 years or until
      development of CSME. Ophthalmologic examinations, including best-corrected visual
      acuity, fundus photography and optical coherence tomography (OCT), were performed
      at baseline, 6 months and a final visit. RESULTS: A total of 348 patients
      completed study follow-up; 26 eyes developed CSME. Six out of 32 eyes/patients
      presenting subclinical DME at baseline developed CSME (18.7%), while 20 out of
      316 eyes without subclinical DME developed CSME (6.3%). Eyes/patients with
      subclinical DME presented a risk for DME progression 3.686 times higher than that
      of eyes/patients without subclinical DME (95% confidence interval 1.221-7.988).
      CONCLUSIONS: Subclinical DME in eyes with NPDR identified by center point
      thickness measured on a Stratus OCT is a good predictor of CSME development.

PMID- 24080705
TI  - TDP-43 pathology, cognitive decline, and dementia in old age.
AB  - IMPORTANCE: Cognitive decline is a leading cause of disability and death in old
      age but its neurobiological bases are not well understood. OBJECTIVE: To test the
      hypothesis that transactive response DNA-binding protein 43 (TDP-43) is related
      to late-life cognitive decline. DESIGN, SETTING, AND PARTICIPANTS: Longitudinal
      clinical-pathologic cohort study involving more than 40 Catholic groups across
      the United States. A total of 130 older Catholic nuns, priests, and monks
      underwent annual clinical evaluations, including detailed cognitive testing, for
      a mean of 10.1 years prior to death. On neuropathologic examination, we collected
      semiquantitative measures of TDP-43 pathology, density of neuronal
      neurofibrillary tangles, area occupied by amyloid-beta plaques, and the presence
      of alpha-synuclein Lewy bodies from multiple brain regions. Gross and microscopic
      cerebral infarcts and hippocampal sclerosis were also identified. MAIN OUTCOMES
      AND MEASURES: Annual rate of change in a previously established composite measure
      of global cognition during a mean of 10.1 years of annual observation before
      death. RESULTS: Transactive response DNA-binding protein 43 pathology, ranging
      from sparse to severe, was identified in 46% of participants and was associated
      with amyloid plaques, tangles, and hippocampal sclerosis but not neocortical Lewy
      bodies or cerebral infarcts. After controlling for amyloid plaques, tangles, and
      hippocampal sclerosis, TDP-43 pathology was associated with more rapid cognitive
      decline and accounted for nearly as much of the variability in rates of global
      cognitive decline as did tangles. Transactive response DNA-binding protein 43
      pathology had a distinct cognitive profile that differed from other
      neuropathologic processes (related to decline in episodic and working memory but
      not in other cognitive domains), and it was elevated in those who developed
      dementia but not in those with mild cognitive impairment. CONCLUSION AND
      RELEVANCE: The results suggest that TDP-43 is an important brain pathology
      underlying cognitive decline and dementia in old age.

PMID- 24080713
TI  - Are the three canals equally susceptible to benign paroxysmal positional vertigo?
AB  - A prospective study of patients diagnosed with 'single-canal' benign paroxysmal
      positional vertigo (BPPV) was performed. Demographic, etiological and prognostic
      differences between patients with posterior, horizontal and superior canal BPPV
      were studied. A total of 614 patients diagnosed in a period of 11 years and with
      a follow-up period of at least 1 year were included in the study. The posterior
      semicircular canal was affected in 543 casas (88.4%), the horizontal in 39 (6.4%)
      and the superior canal in 32 (5.2%). Final status at the end of the follow-up
      period was better in posterior canal BPPV (95% cure) than in horizontal or
      superior canal BPPV (87% cure in both cases). This may be explained by two facts:
      a poorer initial response to repositioning maneuvers in anterior canal BPPV than
      in BPPV involving the other two canals, and a poorer response to maneuvers in
      recurrences of horizontal canal BPPV.

PMID- 24080700
TI  - Applying insights from biofilm biology to drug development - can a new approach
      be developed?
AB  - Most of the research on bacterial pathogenesis has focused on acute infections,
      but much less is known about the pathogenesis of infections caused by bacteria
      that grow as aggregates in biofilms. These infections tend to be chronic as they
      resist innate and adaptive immune defence mechanisms as well as antibiotics, and
      the treatment of biofilm infections presents a considerable unmet clinical need.
      To date, there are no drugs that specifically target bacteria in biofilms;
      however, several approaches are in early-stage development. Here, we review
      current insights into biofilm physiology and pathology, and discuss how a deep
      insight into the physical and biological characteristics of biofilms can inform
      therapeutic strategies and molecular targets for the development of anti-biofilm
      drugs. 

PMID- 24080710
TI  - Effect of phallic stretch on length of bulbous urethral stricture during
      retrograde urethrography.
AB  - OBJECTIVE: The purpose of this study was to evaluate the effect of phallic
      stretch on bulbous urethral stricture while performing retrograde urethrography
      (RUG). METHODS: Between July 2009 and June 2012, 197 adult males with stricture
      pattern on uroflowmetry underwent RUG. Two films were taken, first without (film
      A) and second after stretching the penis by about 5 cm (film B). 29 cases with
      proximal and distal bulbous strictures were included in the present analysis. The
      data recorded were stricture lengths in films A and B. RESULTS: 12 men had distal
      bulbous or penobulbous stricture (group 1) while 17 had stricture involving the
      proximal bulb (group 2). Mean stricture length in group 1 was 2.82 cm (range 1.2
      4.2 cm) in film A and 4.59 cm (range 3.0-6.4 cm) in film B. In group 2 stricture
      length was 1.76 cm (range 1.0-2.3 cm) in film A and 1.79 cm (range 1.0-2.5 cm) in
      film B. The percentage change in stricture length on stretching was 38.48% (p =
      0.0001) in group 1 and 1.67% (p = 0.8301) in group 2. CONCLUSIONS: The impact of
      phallic stretch on radiographic length during RUG was found to be significant in
      distal bulbous but not in proximal urethral stricture, which is important when
      interpreting the RUG and deciding the management of stricture.

PMID- 24080714
TI  - Promestriene, a specific topic estrogen. Review of 40 years of vaginal atrophy
      treatment: is it safe even in cancer patients?
AB  - Urogenital symptoms resulting from estrogen deficiency are common problems that
      impair quality of life and sexuality. Potentially, one out of three
      postmenopausal women could benefit from a vaginal estrogen therapy, but the fear
      of systemic absorption limits its use. Promestriene used vaginally to relieve
      vaginal atrophy is a locally effective estrogen that has not shown systemic
      estrogenic effects. Thus, it could be a first-line option for those who
      necessitate a minimal or ideally no vaginal absorption, particularly in
      symptomatic cancer patients. There are little data available in the literature,
      mostly consisting of small, open-label, short duration studies, and few
      randomized-controlled studies. After a long-term market experience (almost 40
      years), in 34 countries, and millions of pieces prescribed, the side effects were
      very rarely reported in pharmacovigilance data, whereas the effectiveness to
      relieve atrophy was good. To further improve promestriene safety, especially in
      estrogen-sensitive cancer patients, a very low dose is used from the beginning,
      starting from half or less of the usual dose, and then gradually increased till
      the minimum effective dose, which could further reduce its already minimal
      vaginal absorption. 

PMID- 24080716
TI  - An evaluation of a collaborative, safety focused, nurse-pharmacist intervention
      for improving the accuracy of the medication history.
AB  - OBJECTIVE: To evaluate the impact of a standardized approach to collecting a
      medication history on the accuracy of the admission medication list. METHODS:
      Pharmacists and nurses developed and implemented a structured, systematic
      assessment tool for use by nurses in obtaining a medication history. The tool was
      first evaluated with nursing students in an educational setting using mock
      patients and simulated scenarios. The number and type of medication errors
      (omissions) were compared between controls and those using the tool. Based on the
      findings from this phase of the study, we refined the tool and then implemented
      it on four medical/surgical units in a large academic teaching hospital and a
      smaller, affiliated community hospital. We compared medication error rates using
      hospital safety report records and discrepancies (i.e., delays in ordering,
      omissions) before and after implementation of the tool. RESULTS: Accuracy of the
      medication history improved significantly with student nurses who used the tool
      versus those who did not (87% versus 74%, P = 0.010). We were unable to evaluate
      the numbers of medication discrepancies in the academic medical center because of
      a lack of availability of electronic admission history and physical reports
      during the study period. At the community hospital, there was a significant
      increase in the percentage of patients without medication discrepancies (before =
      20% versus after = 42%, P = 0.017), a significant reduction of minor medication
      omissions during the hospital stay (1.10 versus post 0.60, P = 0.003) and a trend
      toward the reduction of important drug omissions in the discharge summary (pre
      0.43 [0.71] versus post 0.18 [0.44], P = 0.053). The most common agents involved
      in a delay or omission were multivitamins, laxatives, antidepressants,
      antidiabetic agents, platelet inhibitors, and acid-suppressing agents.
      CONCLUSIONS: The use of a structured tool to systematically obtain a medication
      history produced a measurable improvement in the accuracy of the admission
      medication list by student nurses and a reduction of medication errors in a
      community hospital.

PMID- 24080717
TI  - Trends in computed tomography utilization rates: a longitudinal practice-based
      study.
AB  - OBJECTIVES: Computed tomography (CT) use has increased dramatically over the past
      2 decades, leading to increased radiation exposure at the population level. We
      assessed trends in CT use in a primary care (PC) population from 2000 to 2010.
      METHODS: Trends in CT use from 2000 to 2010 were assessed in an integrated, multi
      specialty group practice. Administrative data were used to identify patients
      associated with a specific primary care provider and all CT imaging procedures.
      Utilization rates per 1000 patients and CT rates by type and medical specialty
      were calculated. RESULTS: Of 179,032 PC patients, 55,683 (31%) underwent CT. Mean
      age (SD) was 31.0 (23.6) years; 53% were female patients. In 2000, 178.5 CT scans
      per 1000 PC patients were performed, increasing to 195.9 in 2010 (10% absolute
      increase, P = 0.01). Although utilization rates across the 10-year period
      remained stable, emergency department (ED) CT examinations rose from 41.1 per
      1000 in 2000 to 74.4 per 1000 in 2010 (81% absolute increase, P < 0.01). CT
      abdomen accounted for more than 50% of all CTs performed, followed by CT other
      (19%; included scans of the spine, extremities, neck and sinuses), CT chest
      (16%), and CT head (14%). Top diagnostic CT categories among those undergoing CT
      were abdominal pain, lower respiratory disease, and headache. CONCLUSIONS:
      Although utilization rates across the 10-year period remained stable, CT use in
      the ED substantially increased. CT abdomen and CT chest were the two most common
      studies performed and are potential targets for interventions to improve the
      appropriateness of CT use.

PMID- 24080718
TI  - The reliability of AHRQ Common Format Harm Scales in rating patient safety
      events.
AB  - OBJECTIVES: A study was conducted to determine the reliability of Agency for
      Healthcare Research & Quality (AHRQ) Common Format Harm Scale versions 1.1 and
      1.2 in rating patient safety events among users of the UHC Patient Safety Net, a
      Web-based incident reporting tool. METHODS: To test interrater agreement, UHC
      developed a survey tool consisting of patient event scenarios. In 2011, a survey
      evaluating Harm Scale v.1.1 was distributed to 921 quality, risk, and safety
      (QRS) managers at 89 organizations; in 2012, a second survey evaluating Harm
      Scale v.1.2 was sent to 13,280 managers at 102 organizations. RESULTS: Regardless
      of the version used, in 3 of 9 scenarios, fewer than 60% of respondents agreed on
      a single score. Interrater agreement increased for certain event scenarios with
      v.1.2 but decreased for other scenarios. Interrater reliability was moderate for
      both v.1.1 (k = 0.51) and v.1.2 (k = 0.47). Interrater agreement improved in
      v.1.2 when results were limited to more experienced raters but still remained in
      the moderate range (k = 0.58). CONCLUSIONS: AHRQ Common Format Harm Scale v.1.1
      and v.1.2 both had moderate interrater reliability. Using Harm Scale v.1.1,
      respondents had difficulty distinguishing "injury limited to additional
      treatment" from "temporary harm," whereas, using Harm Scale v.1.2, respondents
      had difficulty distinguishing moderate harm from one of the adjacent levels-mild
      or severe harm. This study provides valuable data that can inform harm scale
      revision to improve the quality of aggregate safety data used to define and
      direct safety efforts.

PMID- 24080719
TI  - Safety in numbers: the development of Leapfrog's composite patient safety score
      for U.S. hospitals.
AB  - OBJECTIVE: To develop a composite patient safety score that provides patients,
      health-care providers, and health-care purchasers with a standardized method to
      evaluate patient safety in general acute care hospitals in the United States.
      METHODS: The Leapfrog Group sought guidance from a panel of national patient
      safety experts to develop the composite score. Candidate patient safety
      performance measures for inclusion in the score were identified from publicly
      reported national sources. Hospital performance on each measure was converted
      into a "z-score" and then aggregated using measure-specific weights. A reference
      mean score was set at 3, with scores interpreted in terms of standard deviations
      above or below the mean, with above reflecting better than average performance.
      RESULTS: Twenty-six measures were included in the score. The mean composite score
      for 2652 general acute care hospitals in the United States was 2.97 (range by
      hospital, 0.46-3.94). Safety scores were slightly lower for hospitals that were
      publicly owned, rural in location, or had a larger percentage of patients with
      Medicaid as their primary insurance. CONCLUSIONS: The Leapfrog patient safety
      composite provides a standardized method to evaluate patient safety in general
      acute care hospitals in the United States. While constrained by available data
      and publicly reported scores on patient safety measures, the composite score
      reflects the best available evidence regarding a hospital's efforts and outcomes
      in patient safety. Additional analyses are needed, but the score did not seem to
      have a strong bias against hospitals with specific characteristics. The composite
      score will continue to be refined over time as measures of patient safety evolve.

PMID- 24080720
TI  - A tool to determine financial impact of adverse events in health care: healthcare
      quality calculator.
AB  - OBJECTIVES: Hospital leaders lack tools to determine the financial impact of poor
      patient outcomes and adverse events. To provide health-care leaders with decision
      support for investments to improve care, we created a tool, the Healthcare
      Quality Calculator (HQCal), which uses institution-specific financial data to
      calculate impact of poor patient outcomes or quality improvement on present and
      future margin. METHODS: Excel and Web-based versions of the HQCal were based on a
      cohort study framework and created with modular components including major
      drivers of cost and reimbursement. RESULTS: The Healthcare Quality Calculator
      (HQCal) compares payment, cost, and profit/loss for patients with and without
      poor outcomes or quality issues. Cost and payment information for groups with and
      without quality issues are used by the HQCal to calculate profit or loss.
      Importantly, institution-specific payment and cost data are used to calculate
      financial impact and attributable cost associated with poor patient outcomes,
      adverse events, or quality issues. Because future cost and reimbursement changes
      can be forecast, the HQCal incorporates a forward-looking component. The
      flexibility of the HQCal was demonstrated using surgical site infections after
      abdominal surgery and postoperative surgical airway complications. CONCLUSIONS:
      The Healthcare Quality Calculator determines financial impact of poor patient
      outcomes and the benefit of initiatives to improve quality. The calculator can
      identify quality issues that would provide the largest financial benefit if
      improved; however, it cannot identify specific interventions. The calculator
      provides a tool to improve transparency regarding both short- and long-term
      financial consequences of funding, or failing to fund, initiatives to close gaps
      in quality or improve patient outcomes.

PMID- 24080721
TI  - Emergency department experience with nonoral contrast computed tomography in the
      evaluation of patients for appendicitis.
AB  - STUDY OBJECTIVES: The American College of Radiology lists oral contrast as an
      institution-specific option in the evaluation of right lower quadrant pain.
      Previous literature indicates that an accurate assessment for appendicitis can be
      made by CT using IV contrast alone, with significant time savings from
      withholding oral contrast. Before 2010, the protocol for CT use in the evaluation
      of possible appendicitis or undifferentiated abdominal pain routinely included
      oral contrast. The purpose of this study was to determine the incidence of repeat
      CT scans with oral contrast for the purpose of arriving at a final disposition in
      patients undergoing evaluation for abdominal pain. This analysis was also to
      determine if the general surgery service was willing and able to make accurate
      clinical determinations to operate without the use of oral contrast. METHODS:
      Consecutive abdominal CTs for nontraumatic abdominal pain were evaluated
      retrospectively over a 7-month period from January through July 2010. CT scans
      performed for evaluation of trauma were eliminated, as were cases in patients
      with known previous appendectomy or in cases in which appendicitis was not a
      consideration. Follow-up was by chart review over the ensuing 30 days for
      complications or need for surgery, which was not detected after the initial CT
      scan. The study was conducted at a teaching hospital, level I trauma center with
      an annual ED census of 99,000 visits. RESULTS: A total of 311 CT scans met the
      study criteria. No cases of appendicitis were missed. Two patients were operated
      on based upon inflammatory findings in the right lower quadrant, one with
      typhlitis, the second with possible inflammatory bowel disease versus typhlitis.
      In each case, the diagnosis was made by CT, but the surgery service chose to
      operate based on clinical findings. Sixteen (5.14%; 95% CI, 3.2%-8.2%) cases of
      acute appendicitis were accurately identified. A normal appendix was visualized
      in 125 (40.2 %; 95% CI, 34.9-45.7) patients. No patients (0%; 95% CI, 0%-1.2%)
      required a repeat CT scan with oral contrast as part of the workup. On 30-day
      follow-up by chart review, no (0%; 95% CI, 0%-1.2%) significant surgical problems
      were identified, and no cases of missed appendicitis were identified.
      CONCLUSIONS: Abdominal CT scan without the use of oral contrast is accurate to
      allow for appropriate decision making by emergency physicians and general
      surgeons. In our series, no patients required repeat scanning. Further assessment
      by larger studies is appropriate.

PMID- 24080722
TI  - Variability of patient safety culture in Belgian acute hospitals.
AB  - OBJECTIVES: The aim of this study was to measure differences in safety culture
      perceptions within Belgian acute hospitals and to examine variability based on
      language, work area, staff position, and work experience. METHODS: The Hospital
      Survey on Patient Safety Culture was distributed to hospitals participating in
      the national quality and safety program (2007-2009). Hospitals were invited to
      participate in a comparative study. Data of 47,136 respondents from 89 acute
      hospitals were used for quantitative analysis. Percentages of positive response
      were calculated on 12 dimensions. Generalized estimating equations models were
      fitted to explore differences in safety culture. RESULTS: Handoffs and
      transitions, staffing, and management support for patient safety were considered
      as major problem areas. Dutch-speaking hospitals had higher odds of positive
      perceptions for most dimensions in comparison with French-speaking hospitals.
      Safety culture scores were more positive for respondents working in pediatrics,
      psychiatry, and rehabilitation compared with the emergency department, operating
      theater, and multiple hospital units. We found an important gap in safety culture
      perceptions between leaders and assistants within disciplines. Administration and
      middle management had lower perceptions toward patient safety. Respondents
      working less than 1 year in the current hospital had more positive safety culture
      perceptions in comparison with all other respondents. CONCLUSIONS: Large
      comparative databases provide the opportunity to identify distinct high and low
      scoring groups. In our study, language, work area, and profession were identified
      as important safety culture predictors. Years of experience in the hospital had
      only a small effect on safety culture perceptions.

PMID- 24080723
TI  - Understanding safety culture in long-term care: a case study.
AB  - OBJECTIVES: This case study aimed to understand safety culture in a high-risk
      secured unit for cognitively impaired residents in a long-term care (LTC)
      facility. Specific objectives included the following: diagnosing the present
      level of safety culture maturity using the Patient Safety Culture Improvement
      Tool (PSCIT), examining the barriers to a positive safety culture, and
      identifying actions for improvement. METHODS: A mixed methods design was used
      within a secured unit for cognitively impaired residents in a Canadian nonprofit
      LTC facility. Semistructured interviews, a focus group, and the Modified Stanford
      Patient Safety Culture Survey Instrument were used to explore this topic. Data
      were synthesized to situate safety maturity of the unit within the PSCIT adapted
      for LTC. RESULTS: Results indicated a reactive culture, where safety systems were
      piecemeal and developed only in response to adverse events and/or regulatory
      requirements. A punitive regulatory environment, inadequate resources, heavy
      workloads, poor interdisciplinary collaboration, and resident safety training
      capacity were major barriers to improving safety. CONCLUSIONS: This study
      highlights the importance of understanding a unit's safety culture and identifies
      the PSCIT as a useful framework for planning future improvements to safety
      culture maturity. Incorporating mixed methods in the study of health care safety
      culture provided a good model that can be recommended for future use in research
      and LTC practice.

PMID- 24080724
TI  - Perceptions of medical errors in cancer care: an analysis of how the news media
      describe sentinel events.
AB  - OBJECTIVE: To analyze the print news media's coverage of sentinel events
      involving cancer patients. METHODS: Using LexisNexis, we identified English
      language newspaper articles covering medical errors in cancer care between
      January 1, 2000, and December 31, 2010. Articles were coded for 3 major themes
      using a standardized abstraction instrument: narrative statements and point of
      view most prominently represented, attribution of blame, and orientation toward
      patient safety. We also abstracted country where the newspaper was published,
      type of error event, and extent of patient harm. RESULTS: We analyzed 64 articles
      from 37 print newspaper syndications that circulated in 6 countries/regions.
      Reports of medical errors rarely were framed from the point of view of a safety
      expert or the responsible clinician (13% and 3%, respectively) compared with the
      patient and legal points of view (both 30%). Articles held individual clinicians
      (41%) and hospital systems (28%) responsible for most errors. Four in 10 articles
      failed to present medical errors as "systems" problems. Article perspective
      varied considerably by country, with 53% of articles from the UK and 63% from
      Australia and New Zealand judged as negatively slanted compared with 14% in the
      United States and Canada. CONCLUSIONS: In reports of medical errors involving
      cancer patients, the news media regularly blame individual clinicians for
      mistakes and fail to present a systems-based understanding of these events.

PMID- 24080725
TI  - A CMOS wireless biomolecular sensing system-on-chip based on polysilicon nanowire
      technology.
AB  - As developments of modern societies, an on-field and personalized diagnosis has
      become important for disease prevention and proper treatment. To address this
      need, in this work, a polysilicon nanowire (poly-Si NW) based biosensor system-on
      chip (bio-SSoC) is designed and fabricated by a 0.35 MUm 2-Poly-4-Metal (2P4M)
      complementary metal-oxide-semiconductor (CMOS) process provided by a
      commercialized semiconductor foundry. Because of the advantages of CMOS system-on
      chip (SoC) technologies, the poly-Si NW biosensor is integrated with a chopper
      differential-difference amplifier (DDA) based analog-front-end (AFE), a
      successive approximation analog-to-digital converter (SAR ADC), and a
      microcontroller to have better sensing capabilities than a traditional Si NW
      discrete measuring system. In addition, an on-off key (OOK) wireless transceiver
      is also integrated to form a wireless bio-SSoC technology. This is pioneering
      work to harness the momentum of CMOS integrated technology into emerging bio
      diagnosis technologies. This integrated technology is experimentally examined to
      have a label-free and low-concentration biomolecular detection for both Hepatitis
      B Virus DNA (10 fM) and cardiac troponin I protein (3.2 pM). Based on this work,
      the implemented wireless bio-SSoC has demonstrated a good biomolecular sensing
      characteristic and a potential for low-cost and mobile applications. As a
      consequence, this developed technology can be a promising candidate for on-field
      and personalized applications in biomedical diagnosis. 

PMID- 24080726
TI  - Crystal structure of mammalian cryptochrome in complex with a small molecule
      competitor of its ubiquitin ligase.

PMID- 24080727
TI  - How to correct chromosomal trisomy.
AB  - Trisomy 21 in human causes Down syndrome, a common chromosome disorder with
      devastating phenotypes ranging from early death in utero to intellectual
      disability together with an array of physical anomalies and late-onset diseases.
      In a recent study published in Nature, Jeanne Lawrence and her colleagues
      restored normal gene expression in trisomy 21 cells by silencing the extra
      chromosome using XIST, the non-coding RNA that normally silences one X chromosome
      in females; this improved growth and differentiation of neural cells, which
      offers hope that some deleterious effects of the trisomy could be reversed to
      improve this incurable disease. 

PMID- 24080728
TI  - MicroRNA-155 broadly orchestrates inflammation-induced changes of microRNA
      expression in breast cancer.

PMID- 24080729
TI  - Discontinuation of antidepressants in remitted anxiety disorder patients: the
      need for strategies to prevent relapse.

PMID- 24080733
TI  - Diabetes: Insulin pumps in children with T1DM--we told you so.

PMID- 24080734
TI  - Obesity: Bariatric surgery, weight loss and bone.

PMID- 24080737
TI  - Diabetes: Regulation of hyperglycaemia--too much can be heart-breaking.

PMID- 24080732
TI  - Glucocorticoid sensitivity in health and disease.
AB  - Glucocorticoids regulate many physiological processes and have an essential role
      in the systemic response to stress. For example, gene transcription is modulated
      by the glucocorticoid-glucocorticoid receptor complex via several mechanisms. The
      ultimate biologic responses to glucocorticoids are determined by not only the
      concentration of glucocorticoids but also the differences between individuals in
      glucocorticoid sensitivity, which is influenced by multiple factors. Differences
      in sensitivity to glucocorticoids in healthy individuals are partly genetically
      determined by functional polymorphisms of the gene that encodes the
      glucocorticoid receptor. Hereditary syndromes have also been identified that are
      associated with increased and decreased sensitivity to glucocorticoids. As a
      result of their anti-inflammatory properties, glucocorticoids are widely used in
      the treatment of allergic, inflammatory and haematological disorders. The variety
      in clinical responses to treatment with glucocorticoids reflects the considerable
      variation in glucocorticoid sensitivity between individuals. In immune-mediated
      disorders, proinflammatory cytokines can induce localized resistance to
      glucocorticoids via several mechanisms. Individual differences in how tissues
      respond to glucocorticoids might also be involved in the predisposition for and
      pathogenesis of the metabolic syndrome and mood disorders. In this Review, we
      summarize the mechanisms that influence glucocorticoid sensitivity in health and
      disease and discuss possible strategies to modulate glucocorticoid
      responsiveness. 

PMID- 24080738
TI  - Cosegregation of focal segmental glomerulosclerosis in a family with familial
      partial lipodystrophy due to a mutation in LMNA.
AB  - BACKGROUND AND AIM: Focal segmental glomerulosclerosis (FSGS) is a common cause
      of idiopathic nephrotic syndrome in adults (35%). A number of genetic and
      familial forms of FSGS have been recognized. Here, we report a large pedigree
      with a pathogenic mutation in LMNA (R349W) in which four members were found to
      have biopsy-proven FSGS. The LMNA gene codes for lamins A and C, major components
      of the nuclear lamina which function in nuclear architecture, integrity and the
      regulation of gene expression. METHODS: Pedigree screening and mutation analysis
      of LMNA gene in all family members. Renal biopsies were performed in proteinuric
      patients. A molecular 3D model of the familial LMNA mutation was constructed.
      RESULTS: There were a total of 16 affected members from four generations, 12 of
      whom were found to carry the germline LMNA mutation. All affected adults had
      clinical features of familial partial lipodystrophy (FPLD) of the non-Dunnigan
      variety. Four patients within the same generation presented with a variable
      degree of renal impairment and proteinuria. Renal biopsies from all four revealed
      FSGS. The familial mutation is a missense change (R349W) in exon 6 of LMNA
      (c.1045C>T). CONCLUSIONS: We report a genetic link between LMNA and biopsy-proven
      FSGS in a large pedigree with FPLD. This unexpected association extends the
      disease spectrum of LMNA to the kidney and suggests that the physiological role
      of LMNA could be relevant to the maintenance of glomerular structure and
      function.

PMID- 24080739
TI  - TB treatment in a chronic complex emergency: treatment outcomes and experiences
      in Somalia.
AB  - BACKGROUND: Medecins Sans Frontieres (MSF) provides TB treatment in Galkayo and
      Marere in Somalia. MSF international supervisory staff withdrew in 2008 owing to
      insecurity but maintained daily communication with Somali staff. In this paper,
      we aimed to assess the feasibility of treating TB in a complex emergency setting
      and describe the programme adaptations implemented to facilitate acceptable
      treatment outcomes. METHODS: Routinely collected treatment data from 2005-2012
      were retrospectively analysed. In multivariate analyses, factors associated with
      successful outcome (cure or completion versus failure, death and default) were
      assessed, including the presence of international supervisory staff. Informal
      interviews were conducted with Somali staff regarding programmatic factors
      affecting patient management and perceived reasons for default. RESULTS: In
      total, 6167 patients were admitted (34.8% female; median age 24.0 years [IQR 13.0
      38.0 years]). Treatment success was 79% (programme range 69-87%). Presence of
      international staff did not improve outcomes (adjusted OR 0.85, 95% CI 0.66-1.09;
      p=0.27). Perceived reasons for default included being away from family, nomadic
      group, insecurity, travel cost, need to return to grazing land or feeling better.
      CONCLUSIONS: Despite the challenges, a high percentage of patients were
      successfully treated. Treatment outcomes were not adversely affected by
      withdrawal of international supervisory staff.

PMID- 24080740
TI  - Dorsal stabilization of atlantoaxial subluxation using non-absorbable sutures in
      toy breed dogs.
AB  - OBJECTIVE: To describe a novel dorsal technique for stabilization of atlantoaxial
      subluxation in toy breed dogs using 3-metric nylon suture. STUDY: Retrospective
      study. ANIMALS: Fifteen toy breed dogs with a body weight of 2 kg or less with
      atlantoaxial subluxation. MATERIALS AND METHODS: The atlantoaxial joint of each
      dog was surgically stabilized through a dorsal approach by placing a double
      strand of non-absorbable, 3-metric, nylon suture material between the dorsal
      muscles of the atlanto-occipital and the atlantoaxial joint muscles. Pre- and
      postoperative neurological status, diagnostic imaging, and complications were
      reviewed. Clinical follow-up examination was performed at six months. For long
      term assessment, a telephone follow-up was performed. RESULTS: No intra-operative
      complications were observed. Functional improvement occurred in 12 dogs. One dog
      did not improve and four dogs required revision surgery. In two of those four
      cases, suture material breakage was proven and it was suspected in the other two.
      Two cases underwent a second dorsal approach with the same suture material and
      two cases underwent a ventral approach (transarticular fixation and multiple
      implants embedded with polymethylmethacrylate). CONCLUSIONS: Dorsal stabilization
      using 3-metric nylon may be adequate as a safe, effective, and simple alternative
      technique for atlantoaxial stabilization in toy breed dogs of <=1.5 kg of weight,
      in which the use of ventral screws and pins is challenging.

PMID- 24080741
TI  - alpha-Synuclein in Parkinson's disease: pathogenic function and translation into
      animal models.
AB  - Parkinson's disease is a common neurodegenerative disease characterised by the
      loss of dopaminergic neurons in the substantia nigra pars compacta and the
      formation of alpha-synuclein aggregates found in Lewy bodies throughout the
      brain. Several alpha-synuclein transgenic mouse models have been generated, as
      well as viral-mediated overexpression of wild-type and mutated alpha-synuclein to
      mimic the disease and to delineate the pathogenic pathway of alpha-synuclein
      mediated toxicity and neurodegeneration. In this review, we will recapitulate
      what we have learned about the function of alpha-synuclein and alpha-synuclein
      mediated toxicity through studies of transgenic animal models, inducible animal
      models and viral-based models.

PMID- 24080742
TI  - Dielectric polarization, anisotropy and nonradiative energy transfer into
      nanometre-scale thin semiconducting films.
AB  - A common problem of nonradiative energy transfer (NRET) from a small energy donor
      into a neighbouring energy acceptor layer is addressed with the emphasis on the
      layer thickness dependence. Two complementary approaches are employed to study
      dielectric polarization effects on NRET into thin films: a macroscopic analysis
      treating the acceptor layer as a continuum characterized by a frequency-dependent
      dielectric function, and a direct modelling utilizing discrete acceptor lattices,
      each of the acceptors being a polarizable point dipole. Explicit illustrations
      are provided of an interesting phenomenon, when NRET into thinner films can
      counter-intuitively be more efficient than NRET into thicker films. We show that
      this phenomenon may take place for a broad range of the acceptor polarization
      responses, including metallic-like and insulating behaviour as well as responses
      with weak and strong dissipation. The spectral vicinity of a strong dielectric
      resonance in the acceptor layer is studied as a specific example. The role of
      geometry-derived and intrinsic anisotropy of the acceptor response is clarified
      in the illustrations. Our results suggest that NRET optimization might be
      possible in the design of hybrid nanostructures, where the geometry of the
      structures is better matched with spectral properties of donor and acceptor
      subsystems.

PMID- 24080743
TI  - Electronic cigarettes: a short review.
AB  - Marketed since 2004 as an alternative to nicotine delivery and advertised as a
      valid means to smoking cessation, the electronic (e)-cigarette has been the
      subject of much controversy but very little experimental study. This review
      provides a brief summary of the current knowledge of this product. Propylene
      glycol and glycerol, the main ingredients of the fluid that is vaporized, have
      proved to be harmless in the fog machines of the entertainment industry. However,
      in the case of the e-cigarette fluid, the composition is not properly labeled:
      additives like nicotine and flavors vary between and within brands and
      contamination with various chemicals has been detected. The short-term toxicity
      seems low, but the long-term toxicity is unknown. The usefulness of the e
      cigarette in smoking cessation has still to be clinically established.

PMID- 24080744
TI  - Clinical and prognostic features of rectal neuroendocrine tumors.
AB  - BACKGROUND: Rectal neuroendocrine tumors (NETs) are among the most common NETs.
      The aim was to validate European Neuroendocrine Tumor Society (ENETS)/North
      American Neuroendocrine Tumor Society (NANETS) staging and grading systems with
      regard to clinical outcomes. METHODS: A comprehensive database was constructed
      from existing databases of the Mount Sinai Division of Gastrointestinal Pathology
      and the Carcinoid Cancer Foundation. Analysis was performed on 141 patients
      identified with rectal NETs seen at Mount Sinai Hospital between 1972 and 2011.
      RESULTS: The median age was 52.7 years; 43% were males. Average tumor size was
      0.88 cm. NETs <1 cm accounted for 75.6% of the tumors. Stage I, II, III and IV
      accounted for 79.4, 2.8, 5.0 and 12.8% of the tumors, respectively. G1 tumors
      accounted for 88.1%, G2 8.3% and G3 3.6%. Of G1 tumors, 94.6% were stage I and
      5.4% were stage IV. The median survival time for all 141 patients was 6.8 years
      (range, 0.8-34.7 years). The overall 5-year survival rate was 84.4%. The 5-year
      survival rates for patients in stages I-IV were 92.7, 75.0, 42.9 and 33.2%,
      respectively. The 5-year survival rates for patients with G1-G3 tumors were 87.7,
      47.6 and 33.3%, respectively. Univariate analysis of increased survival showed
      significance for lower stage, lower grade, smaller size, absence of symptoms and
      endoscopically treated tumors. Multivariate analysis showed that stage alone was
      statistically significant as the strongest predictor of survival. CONCLUSION: The
      results of our study validated ENETS/NANETS guidelines for staging and grading of
      rectal NETs in the US setting of a tertiary referral center. Staging according to
      ENETS/NANETS guidelines should be used in the treatment algorithm rather than
      size alone.

PMID- 24080745
TI  - Myoglobin removal using high-volume high-flux hemofiltration in patients with
      oliguric acute kidney injury.
AB  - BACKGROUND: Rhabdomyolysis can cause acute kidney injury (AKI). It remains
      controversial whether or not myoglobin can be removed from the circulation with
      extracorporeal therapy and decrease the incidence of AKI. Therefore, we examined
      myoglobin removal in a series of 11 patients with oliguric AKI treated with high
      volume hemofiltration. METHODS: Patients received prefilter hemofiltration using
      a polysulphone filter with a molecular size cutoff of 65 kDa and a surface area
      of 1.7 m(2). Sieving coefficients and myoglobin clearances were calculated at 6,
      12, and 24 h after the start of hemofiltration. RESULTS: The mean sieving
      coefficient was 0.158, and the mean myoglobin clearance was 8.7 ml/min.
      CONCLUSION: Despite the use of high-volume hemofiltration, the removal of
      myoglobin was negligible. In patients with normal renal function, the anticipated
      amount of extracorporeal removal would not significantly impact renal exposure to
      myoglobin.

PMID- 24080746
TI  - Risk perception and emotional coping: a pathway for behavioural addiction?
AB  - This article summarizes current concepts of the working memory with regard to its
      role within emotional coping strategies. In particular, it focuses on the fact
      that the limited capacity of the working memory to process now-relevant
      information can be turned into an advantage, when the individual is occupied by
      dealing with unpleasant emotion. Based on a phenomenon known as dual-task
      interference (DTI), this emotion can be chased by intense arousal due to clearly
      identifiable external stressors. Thus, risk perception might be used as a 'DTI
      inductor' that allows avoidance of unpleasant emotion. Successful mastery of risk
      adds a highly relevant dopaminergic component to the overall experience. The
      resulting mechanism of implicit learning may contribute to the development of a
      behavioural addiction. Besides its putative effects in the development of a
      behavioural addiction, the use of DTI might be of a more general interest for the
      clinical practice, especially in the field of psychotherapy.

PMID- 24080747
TI  - Gene expression profiles of sodium-dependent vitamin C transporters in mice after
      alcohol consumption.
AB  - Alcoholic liver disease (ALD) is a serious liver problem in western countries.
      Our previous study has demonstrated that vitamin C plays a protective role in
      ALD. The vitamin C homeostasis is tightly regulated by sodium-dependent vitamin C
      transporters (SVCTs) 1 and 2. But the role of two SVCTs in ALD is less
      understood. In this study, we examined the expression patterns of two SVCTs in
      mice after alcohol consumption. Our results suggested that alcohol consumption
      obviously increased the expression of two SVCTs in liver and SVCT1 in kidney and
      intestine, which is important for vitamin C absorption. Vitamin C supplement
      increased the sera vitamin C content and ameliorated the symptom of ALD.
      Intestinal absorption and renal re-absorption mediated by SVCT1 are key factors
      to increase the sera vitamin C content after alcohol consumption. We proposed
      that both reactive oxygen species and low vitamin C concentration regulate the
      expression of SVCTs, and the protective role of vitamin C is mediated by
      suppressing the stability of hypoxia-inducible factor-1alpha. Thus, our study is
      significant for the understanding of vitamin C homeostasis in ALD and for better
      use of other antioxidants in ALD therapy. 

PMID- 24080749
TI  - Clinical activity of lenalidomide in visceral human immunodeficiency virus
      related Kaposi sarcoma.
AB  - IMPORTANCE: Curative treatment of aggressive Kaposi sarcoma (KS) with
      conventional chemotherapy in human immunodeficiency virus (HIV)-infected patients
      remains difficult. The administration of thalidomide, an immunomodulatory drug
      with antiangiogenic effects, is limited by its toxicity. This engenders interest
      in evaluating thalidomide analogues such as lenalidomide with better toxicity
      profiles. To our knowledge, we describe for the first time a patient with
      visceral KS successfully treated with lenalidomide. OBSERVATIONS: A man with
      advanced visceral HIV-related KS progressing after 11 months of highly active
      antiretroviral therapy (HAART) and 2 lines of conventional chemotherapy
      (pegylated liposomal doxorubicin and docetaxel) was treated with lenalidomide on
      a compassionate use basis. He showed a rapid partial response without any
      substantial adverse effect but experienced relapse after 5 months of treatment,
      in a context of virologic failure. CONCLUSIONS AND RELEVANCE: Similar to our
      observation, good partial response without toxic effects has been reported in 3
      patients with only skin involvement. Because immune reconstitution syndrome may
      occur in HIV-infected patients with KS undergoing HAART, KS improvement may be
      partly explained by immune recovery. An ongoing US phase 1/2 trial will better
      evaluate the efficacy and tolerance of lenalidomide in patients with HIV-related
      KS with and without visceral involvement.

PMID- 24080750
TI  - Evaluation of the personalized bar-code identification card to verify high-risk,
      high-alert medications.
AB  - An effective intervention to decrease medication errors related to high-risk,
      high-alert medications is to implement double checks and second verification
      using the five rights of medication administration. To evaluate the effectiveness
      and use of the Personalized Bar-Code Identification card in verifying high-risk,
      high-alert medications, the High-Risk, High-Alert Medication Verification Audit
      Tool was used to collect data from the medical records of patients who received
      high-risk, high-alert medications in four ICUs. Data were collected for
      administered high-risk, high-alert medication, primary registered nurses who
      administered the high-risk, high-alert medication, and secondary registered
      nurses who verified the medication. The percentage of medications that were "not
      verified," "Personalized Bar-Code Identification verified," and "verified" using
      a method other than the Personalized Bar-Code Identification was calculated and
      compared using Z tests for two proportions. The percentage of Personalized Bar
      Code Identification-verified medications (83.5%) was significantly higher than
      the percentage of medications that were not verified (10.9%) (Z = 38.43, P <
      .05). Also, the difference between the proportion of the Personalized Bar-Code
      Identification-verified medications and those that were verified using another
      method (5.6%) was significant (Z = 41.42, P < .05). The results show that nurses
      generally tend to follow the standardized procedure for verifying high-risk, high
      alert medications in the four ICUs. 

PMID- 24080751
TI  - Eliminating errors in vital signs documentation.
AB  - This study compared two methods of documenting vital signs: a traditional method
      where staff wrote vital signs on paper then keyed into an electronic medical
      record and a wireless system that downloaded vital signs directly into an
      electronic medical record. The study design was pretest and posttest. Sixty-four
      sets of vital signs were evaluated prior to the implementation of a wireless
      download system and 66 sets of vital signs were evaluated after. To compare the
      error rates for the two methods, chi tests were used, and t tests were used to
      compare the elapsed time. Questionnaires relating to the clinicians' experiences
      were analyzed qualitatively. The paper vital signs recording had an error rate of
      18.75% and the wireless system has an error rate of 0% (P < .001). The mean (SD)
      elapsed time from when the vital signs were taken until they were available in
      the electronic medical record was 38.53 (32.87) minutes for the paper method and
      5.06 (6.59) minutes for the wireless method (P < .001). The electronic vital
      signs documentation system resulted in significantly fewer errors and shorter
      elapsed time when compared with the paper system. 

PMID- 24080752
TI  - Formative research for the development of an interactive web-based sexually
      transmitted disease management intervention for young women.
AB  - Sexually transmitted diseases are common among young women and effective self
      management is foundational to improving health outcomes and preventing negative
      sequelae. Advances in technology create the opportunity for innovative delivery
      methods of self-management interventions. However, it is essential to conduct
      formative research with the target population to identify both the needs and the
      preferences for the content and delivery method of a sexually transmitted disease
      self-management intervention prior to intervention development. Eight focus
      groups were conducted with 35 young women between 18 and 24 years of age. We
      found that young women strongly support the use of a Web-based intervention to
      provide sexually transmitted disease self-management guidance. Women were
      interested in receiving comprehensive management information from the perspective
      of both clinicians and other women who have experienced a sexually transmitted
      disease. There was a clear interest in incorporating new media into the Web-based
      intervention to allow for communication with providers as well as to create
      opportunities for social networking between women. This formative research
      provides critical information about the content and delivery method of a self
      management intervention and gives direction for intervention development that is
      inclusive of varying types of new media to allow for connectivity among users,
      their peers, and clinicians. 

PMID- 24080753
TI  - Mixed-methods approach for measuring the impact of video telehealth on outpatient
      clinic triage nurse workflow.
AB  - Nurse-delivered telephone triage is a common component of outpatient clinic
      settings. Adding new communication technology to clinic triage has the potential
      to not only transform the triage process but also alter triage workflow.
      Evaluating the impact of new technology on an existing workflow is paramount to
      maximizing the efficiency of the delivery system. This study investigated triage
      nurse workflow before and after the implementation of video telehealth using a
      sequential mixed-methods protocol that combined ethnography and time-motion study
      to provide a robust analysis of the implementation environment. Outpatient clinic
      triage using video telehealth required significantly more time than telephone
      triage did, indicating a reduction in nurse efficiency. Despite the increased
      time needed to conduct video telehealth, nurses consistently rated it useful in
      providing triage. Interpretive analysis of the qualitative and quantitative data
      suggests that the increased depth and breadth of data available during video
      triage alter the assessment that triage nurses provide physicians. This in turn
      could affect the time physicians spend formulating a diagnosis and treatment
      plan. While the immediate impact of video telehealth is a reduction in triage
      nurse efficiency, what is unknown is the impact of video telehealth on physician
      and overall clinic efficiency. Future studies should address this area. 

PMID- 24080754
TI  - Shooting a moving target: use of real-time cine magnetic resonance imaging in
      assessment of the small bowel.
AB  - The chronic nature of inflammatory bowel disease (IBD) creates a lifelong effect
      on the morbidity of children affected by the disease. The ability to confidently
      identify and characterize complications resulting from IBD in the pediatric
      patient is of critical importance. Magnetic resonance enterography (MRE) is
      especially valuable in the diagnostic assessment of IBD; however, precise
      elucidation of complications including strictures can be difficult with standard
      MRE sequences. The recent development of faster MRI pulse sequences provides
      rapid, real-time imaging of the intestinal tract. In this review, we describe how
      the addition of cine MRE confidently pinpoints areas of stricture, aids in lesion
      detection and diagnosis, and provides valuable information on intestinal
      motility. 

PMID- 24080755
TI  - Complex traits: Adding complexity to yeast.

PMID- 24080756
TI  - Development: Germ cell poising for totipotency.

PMID- 24080757
TI  - Can assessors in a psychotherapy trial be successfully blinded? Analysis of a
      randomized controlled trial on psychotherapy for refractory insomnia in residual
      depression.

PMID- 24080758
TI  - Is the serum vitamin D-parathyroid hormone relationship influenced by obesity in
      children?
AB  - BACKGROUND/AIMS: Serum 25 hydroxyvitamin D [25(OH)D] and parathyroid hormone
      (PTH) levels correlate inversely. The 25(OH)D level at which PTH is maximally
      suppressed and below which PTH begins to rise (inflection point) has been used to
      define optimum 25(OH)D levels. While serum 25(OH)D levels are lower in obese
      individuals, likely due to sequestration of vitamin D in the adipose tissue, it
      is not known if the lower 25(OH)D levels in obese children are associated with a
      PTH increase in the same manner as it is in normal weight children. METHODS: A
      retrospective record review of children between 2 and 18 years of age (n = 269)
      undergoing simultaneous measurement of serum 25(OH)D and PTH levels was
      performed. RESULTS: The level of serum 25(OH)D below which PTH begins to rise was
      significantly lower (p < 0.001) in overweight/obese children compared to normal
      weight children [12.4 (95% CI 9.8-15.0) vs. 17.0 ng/ml (95% CI 11.4-22.6)].
      CONCLUSIONS: In overweight and obese children, the PTH axis is activated at much
      lower 25(OH)D levels than in normal weight children. These findings are a
      consequence of similar ionized calcium levels in these groups despite lower serum
      25(OH)D levels in obese children.

PMID- 24080759
TI  - Minding the gaps: metabolomics mends functional genomics.

PMID- 24080760
TI  - Conductivity oscillation of surface state of three-dimensional topological
      insulators induced by a linearly polarized terahertz field.
AB  - We have theoretically studied the longitudinal dc conductivity of the surface
      state of three-dimensional (3D) topological insulators (TIs) under a linearly
      polarized (LP) terahertz (THz) field irradiation via the Floquet theory and
      Green's function technique. It was found that, due to the anisotropic quasienergy
      spectrum under the LP light, the longitudinal conductivities parallel and
      perpendicular to the polarized direction of the LP light are not the same. When
      the 3D TI's chemical potential is zero, both of the conductivities undergo an
      oscillation against the electron-field interaction parameter because of the
      contribution of the photon modulated side-band transport at different position.
      The oscillation is dramatically suppressed when the chemical potential is higher
      or lower than zero. There is a pronounced dip in the dc conductivity at a
      specific field frequency twice the chemical potential, which can be seen as a gap
      induced metal-to-insulator transition of the surface state of 3D TIs. As the dc
      conductivity of the surface state of 3D TIs has such a pronounced response to the
      LP THz field, our investigations involving the interaction between TIs and LP THz
      field actually provided the possibility of TI application in THz devices.

PMID- 24080761
TI  - A retrospective study of the short-term complication rate following 750 elective
      elbow arthroscopies.
AB  - Arthroscopy is the gold standard for articular surface examination and is
      commonly advocated for diagnosing and treating cases of canine elbow dysplasia.
      Arthroscopy is generally regarded as a low-risk procedure, however there is a
      paucity of information in the small animal veterinary literature regarding the
      associated complication rates. In a retrospective study spanning a ten year
      period, 750 elective elbow arthroscopies were evaluated. Complications
      necessitating repeat surgery were defined as major, and were documented in 4.8%
      of dogs. Minor perioperative complications occurred in 17.1% dogs. The failure of
      arthroscopic treatment necessitating unplanned conversion to arthrotomy was the
      most frequently encountered complication in this category, having been reported
      in five percent of dogs. Minor postoperative complications occurred in 10.7%
      dogs; these included a worsened postoperative lameness (5.5%), severe pain
      (2.8%), severe swelling (2%), infection (0.2%), and neurapraxia (0.2%). A total
      of 204 dogs returned for a postoperative re-examination and in seven percent,
      lameness was more severe than that noted preoperatively. The results of the study
      show that the major complication rate associated with elective elbow arthroscopy
      is low, but that the minor peri- and postoperative complication rate is
      concerning. These findings will assist veterinarians in their preoperative
      discussions with owners to ensure the achievement of informed consent. 

PMID- 24080762
TI  - Prophylaxis of acute radiation dermatitis with an innovative FDA-approved two
      step skin care system in a patient with head and neck cancer undergoing a platin
      based radiochemotherapy: a case report and review of the literature.
AB  - Radiodermatitis is a very common side effect in cancer treatment often leading to
      therapy delays and diminution of the patients' health state and quality of life.
      Despite a wide range of supportive strategies, radiodermatitis is still a major
      problem necessitating further improvements in prevention and treatment. Lactokine
      is a milk-based protein shown to assist in the reduction of skin redness. The
      treatment is a unique FDA-approved skin care system (R1 and R2). In this case
      presentation we describe the prophylactic use of R1 and R2 in a 63-year-old,
      female patient with a squamous cell carcinoma of the hypopharynx undergoing a
      platin-based chemoradiation. The application was feasible and safe and the
      patient developed only a slight radiodermatitis. To our knowledge this is the
      first report in the literature on the prophylactic use of R1 and R2. Further
      evidence will be provided by a prospective, clinical trial we have launched
      (CREAM-1; study registration in ISRCTN Registry: ISRCTN87302591). We also review
      the literature to give an overview about common strategies in the management of
      radiodermatitis.

PMID- 24080763
TI  - Impact of chronic kidney disease in early invasive versus early conservative
      revascularization strategies in non-ST-segment elevation acute coronary
      syndromes: a population-based study from NHIRD of Taiwan.
AB  - BACKGROUND: Patients with chronic kidney disease (CKD) sustaining a non-ST
      segment elevation acute coronary syndrome (NSTE-ACS) are considered high risk and
      an early invasive strategy (EIS) is often recommended. However, the impact of CKD
      on patients receiving an EIS or an early conservative strategy (ECS) is unclear
      in real-world practice. METHODS: Data were analyzed from the 2005-2008 National
      Health Insurance Research Database (NHIRD) in Taiwan. The diagnosis of CKD was
      based on the International Classification of Disease-9 codes recorded by
      physicians. EIS was defined as coronary angiography with intent to
      revascularization performed within 72 h of symptom onset. The primary endpoint
      was time to first major adverse cardiac event (MACE) comprising cardiovascular
      death, myocardial infarction (MI) and stroke. The secondary endpoints included
      major bleeding (MB), heart failure (HF) and dialysis during admission (DDA).
      RESULTS: 834 patients (466 EIS and 368 ECS) were enrolled and age was 64.3 +/-
      12.6 years. Mean follow-up time was 1,163.96 +/- 19.99 days. In the whole
      population an EIS was associated with a reduction in MACE (HR 0.69; 95% CI 0.50
      0.95, p = 0.024) but not in the CKD population (HR 1.08; 95% CI 0.66-1.78, p =
      0.76). Kaplan-Meier curves showed CKD subjects receiving an EIS had the highest
      MACE, HF and DDA rate (all p < 0.019) and CKD subjects receiving an ECS had the
      highest MB rate (p = 0.018). Cox regression analysis showed CKD predicted higher
      HF and DDA in those receiving an EIS and higher DDA and MB in those receiving an
      ECS. CONCLUSION: An EIS reduced MACE in the overall population, and CKD was a
      poor outcome predictor for both revascularization strategies in NSTE-ACS.

PMID- 24080764
TI  - MicroRNAs in the hypothalamus.
AB  - MicroRNAs (miRNAs) are short (~22 nucleotides) non-coding ribonucleic acid (RNA)
      molecules that negatively regulate the expression of protein-coding genes.
      Posttranscriptional silencing of target genes by miRNA is initiated by binding to
      the 3'-untranslated regions of target mRNAs, resulting in specific cleavage and
      subsequent degradation of the mRNA or by translational repression resulting in
      specific inhibition of protein synthesis. An increasing amount of evidence shows
      that miRNAs control a large number of biological processes and there exists a
      direct link between miRNAs and disease. miRNA molecules are abundantly expressed
      in tissue-specific and regional patterns and have been suggested as potential
      biomarkers, disease modulators and drug targets. The central nervous system is a
      prominent site of miRNA expression. Within the brain, several miRNAs are
      expressed and/or enriched in the region of the hypothalamus and miRNAs have
      recently been shown to be important regulators of hypothalamic control functions.
      The aim of this review is to summarize some of the current knowledge regarding
      the expression and role of miRNAs in the hypothalamus.

PMID- 24080766
TI  - Giga-pixel fluorescent imaging over an ultra-large field-of-view using a flatbed
      scanner.
AB  - We demonstrate a new fluorescent imaging technique that can screen for
      fluorescent micro-objects over an ultra-wide field-of-view (FOV) of ~532 cm(2),
      i.e., 19 cm * 28 cm, reaching a space-bandwidth product of more than 2 billion.
      For achieving such a large FOV, we modified the hardware and software of a
      commercially available flatbed scanner, and added a custom-designed absorbing
      fluorescent filter, a two-dimensional array of external light sources for
      computer-controlled and high-angle fluorescent excitation. We also re-programmed
      the driver of the scanner to take full control of the scanner hardware and
      achieve the highest possible exposure time, gain and sensitivity for detection of
      fluorescent micro-objects through the gradient index self-focusing lens array
      that is positioned in front of the scanner sensor chip. For example, this large
      FOV of our imaging platform allows us to screen more than 2.2 mL of undiluted
      whole blood for detection of fluorescent micro-objects within <5 minutes. This
      high-throughput fluorescent imaging platform could be useful for rare cell
      research and cytometry applications by enabling rapid screening of large volumes
      of optically dense media. Our results constitute the first time that a flatbed
      scanner has been converted to a fluorescent imaging system, achieving a record
      large FOV.

PMID- 24080767
TI  - A multivariate analysis of dermatology missed appointment predictors.

PMID- 24080768
TI  - Efficacy of oral cytarabine ocfosfate and etoposide in the treatment of elderly
      patients with higher-risk myelodysplastic syndromes compared to that in elderly
      acute myeloid leukemia patients.
AB  - BACKGROUND: Elderly acute myeloid leukemia (AML) patients and patients with
      higher-risk myelodysplastic syndromes (MDS) have a much poorer prognosis than
      younger patients despite intensive chemotherapy. METHODS: Ten patients with
      higher-risk MDS and 12 patients with AML over 65 years of age were enrolled into
      this study and received oral induction therapy with cytarabine ocfosfate and
      etoposide. RESULTS: The therapy response rates were 60% in the MDS group and
      41.7% in the AML group. The difference in overall survival among MDS and AML
      patients was not statistically significant. The difference in the median survival
      times of the responsive and nonresponsive groups, which included MDS and AML
      patients, was statistically significant (790 and 174 days, respectively).
      CONCLUSIONS: Based on a comparison of the data of this therapy in elderly higher
      risk MDS patients versus elderly AML patients, we conclude that this therapy is
      well tolerated and can be cost-effective and useful for higher-risk MDS in
      elderly patients.

PMID- 24080769
TI  - Regulatory mechanisms that control T-follicular helper and T-helper 1 cell
      flexibility.
AB  - Following antigenic stimulation, CD4(+) T cells have the potential to
      differentiate into a number of specialized effector cell subtypes. To date, much
      progress has been made in defining the basic molecular mechanisms that regulate
      initial helper T-cell differentiation decisions. Emerging research in the field
      is now uncovering more complexity in the series of events that control helper T
      cell commitment decisions than was previously appreciated. During the commitment
      process, helper T cells need to integrate both signals derived from the T-cell
      receptor and from the surrounding microenvironment. These external signals are
      then translated into internal changes in gene expression potential to ultimately
      define the functional characteristics of the cell. In this review, this topic
      will be discussed from the perspective of T-follicular helper (Tfh) and T-helper
      type 1 (Th1) cell differentiation. The focus will be on examining how the
      cytokine environment is perceived by signaling through signal transducer and
      activator of transcription (STAT) family proteins to initiate fate choices. The
      activities of STAT proteins are then in turn translated into changes in the
      molecular balance between B-cell lymphoma 6 (Bcl-6) and T-box expressed in T
      cells (T-bet), the helper T-cell lineage-specifying transcription factors that
      regulate Tfh and Th1 effector cell differentiation, respectively. Collectively,
      the knowledge of the molecular pathways that regulate Tfh and Th1 commitment have
      provided insight into the relationship between these two specialized helper T
      cell subtypes and the potential for flexibility in their gene programs. 

PMID- 24080770
TI  - Deja vu: the identity of a third lineage of lymphocytes in lampreys.

PMID- 24080771
TI  - Prescribing of drugs for attention-deficit hyperactivity disorder in opioid
      maintenance treatment patients in Norway.
AB  - BACKGROUND: Attention-deficit hyperactivity disorder (ADHD) is a risk factor for
      the development of substance use disorders. Treatment of ADHD with
      psychostimulants in patients on opioid maintenance treatment (OMT) has been
      restricted in Norway. We examined the use of prescribed drugs for ADHD in OMT
      patients and assessed co-medication with other psychotropics. METHODS: Data were
      drawn from the nationwide Norwegian Prescription Database (NorPD), which includes
      all prescriptions filled at pharmacies. The study population included subjects
      >=18 years on OMT during 2008-2010. RESULTS: In 2010, 6,116 patients received OMT
      and 2.8% of these also received ADHD drugs. This percentage is seven times
      greater than that in the gender- and age-specific general population of Norway.
      The prevalence was higher in the youngest patients, while there was no gender
      difference. Methylphenidate was the most commonly used drug for ADHD in OMT
      patients, followed by atomoxetine. 60% of OMT patients filled at least one
      prescription for antidepressants, anxiolytics or hypnotics, and percentages were
      similar for users and non-users of ADHD drugs. CONCLUSION: Treatment with ADHD
      drugs was higher in OMT patients than expected from the general population, but
      was relatively low compared to the prevalence of ADHD in patients with substance
      use disorders reported in the literature.

PMID- 24080772
TI  - Femoral neck stress fracture in children: a case report, up-to-date review, and
      diagnostic algorithm.
AB  - Stress fracture of the femoral neck in skeletally immature individuals is a rare
      condition and generally seen as compressive type. Because the condition may lead
      to disastrous complications, femoral neck stress fracture must also be kept in
      mind in the differential diagnosis of pediatric hip pain. We present a case of
      compressive-type stress fracture of the femoral neck in a 10-year-old girl with
      left hip pain that was sustained for 4 weeks and emphasize the difficulty of
      early diagnosis with only a radiographic evaluation and put forward an algorithm
      for diagnosis and treatment. 

PMID- 24080773
TI  - Multiple-echo data image combination in infants with developmental dysplasia of
      the hip: comparison with conventional T1-weighted and T2-weighted imaging.
AB  - Two-dimensional multiple-echo data image combination (MEDIC) images, as well as
      conventional T1-weighted and T2-weighted images, were obtained for 38 infants
      with developmental dysplasia of the hip. We retrospectively reviewed these images
      to evaluate subjective image quality and femoral head-to-ischium contrast. MEDIC
      images were considered to be of high quality compared with the conventional T1
      weighted (P<0.0001) and T2-weighted images (P<0.05), as well as have a higher
      contrast than conventional T1-weighted and T2-weighted images (P<0.001,
      respectively). In conclusion, MEDIC images provide diagnostic improvement in
      studies on developmental dysplasia of the hip. 

PMID- 24080774
TI  - Ex vivo cyclic mechanical behaviour of 2.4 mm locking plates compared with 2.4 mm
      limited contact plates in a cadaveric diaphyseal gap model.
AB  - OBJECTIVES: To compare the mechanical properties of locking compression plate
      (LCP) and limited contact dynamic compression plate (LC-DCP) constructs in an
      experimental model of comminuted fracture of the canine femur during eccentric
      cyclic loading. METHODS: A 20 mm mid-diaphyseal gap was created in eighteen
      canine femora. A 10-hole, 2.4 mm stainless steel plate (LCP or LC-DCP) was
      applied with three bicortical screws in each bone fragment. Eccentric cyclic
      loadings were applied at 10 Hertz for 610,000 cycles. Quasistatic loading /
      unloading cycles were applied at 0 and 10,000 cycles, and then every 50,000
      cycles. Structural stiffness was calculated as the slope of the linear portion of
      the load-displacement curves during quasistatic loading / unloading cycles.
      RESULTS: No bone failure or screw loosening occurred. Two of the nine LCP
      constructs failed by plate breakage during fatigue testing, whereas no gross
      failure occurred with the LC-DCP constructs. The mean first stiffness of the LCP
      constructs over the course of testing was 24.0% lower than that of constructs
      stabilized by LC-DCP. Construct stiffness increased in some specimens during
      testing, presumably due to changes in bone-plate contact. The first stiffness of
      LC-DCP constructs decreased by 19.4% and that of locked constructs by 34.3%
      during the cycling period. A biphasic stiffness profile was observed: the second
      stiffness was significantly greater than the first stiffness in both groups,
      which allowed progressive stabilization at elevated load levels. CLINICAL
      SIGNIFICANCE: Because LCP are not compressed to the bone, they may have a longer
      working length across a fracture, and thus be less stiff. However, this may cause
      them to be more susceptible to fatigue failure if healing is delayed.

PMID- 24080775
TI  - HCV transmission in industrialized countries and resource-constrained areas.
AB  - HCV is a blood-borne virus transmitted by percutaneous exposure to infected blood
      or blood-derived body fluids. The main routes of transmission are blood
      transfusions, medical procedures and injection drug use. In industrialized
      countries, HCV transmission through blood transfusions has been virtually
      eliminated and iatrogenic transmission occurs only sporadically during local
      breaches of infection control procedures. As most new cases originate from
      injection drug use, harm-reduction programmes (including opiate substitution,
      needle exchange and health education) can greatly reduce HCV transmission.
      Currently, the main approach to reduce the HCV disease burden is by increasing
      awareness of both the public and health-care providers to hepatitis C, enhancing
      screening opportunities and treatment of the infected population. In resource
      limited countries, the priority is reducing transmission through blood
      transfusions and invasive medical procedures. This approach requires training of
      health-care providers and also structural changes and financial investments in
      countries where antibody screening, disposable materials and effective
      sterilization procedures are not routinely available. In these countries,
      reducing the HCV burden has been hampered by limited access to treatment, largely
      owing to the cost of drugs. Access to treatment is moving up on the agenda of
      international and non-governmental organizations in conjunction with the future
      availability of highly efficacious oral drug regimens. 

PMID- 24080777
TI  - Octreotide-induced long QT syndrome in a child with congenital hyperinsulinemia
      and a novel missense mutation (p.Met115Val) in the ABCC8 gene.
AB  - BACKGROUND/AIMS: Congenital hyperinsulinism (CHI) denotes an inappropriate
      secretion of insulin from pancreatic beta-cells in the presence of a low blood
      glucose level due to various genetic causes. Diazoxide is the first-line medical
      treatment for CHI. In case of failure, a somatostatin analogue called octreotide
      is used. A prolonged QT interval is an unusual side effect of octreotide which
      can be lethal if unrecognized. CASE PRESENTATION: We report on a 35-day-old
      infant who was diagnosed with CHI on the 3rd day of his life and underwent
      pancreatectomy due to failure of medical treatment at 8 months. His genetic
      analysis revealed a compound heterozygosity for a novel missense mutation
      (p.Met115Val) and a nonsense mutation (p.Trp1339X) in the ABCC8 gene.
      Furthermore, at the 6th month of follow-up, a long QT (0.49 s) was determined by
      ECG examination, which was normalized following discontinuation of octreotide
      treatment after pancreatectomy. Thus, the long QT was considered to be secondary
      to octreotide medication. CONCLUSION: We recommend ECG monitoring before and
      during octreotide treatment in order to recognize a prolonged QT interval and to
      prevent related complications in cases with congenital hyperinsulinemia.

PMID- 24080779
TI  - Psychological well-being in remitted patients with recurrent depression.

PMID- 24080776
TI  - NAFLD, NASH and liver cancer.
AB  - NAFLD affects a large proportion of the US population and its incidence and
      prevalence are increasing to epidemic proportions around the world. As with other
      liver diseases that cause cirrhosis, NAFLD increases the risk of liver cancer, a
      disease with poor outcomes and limited therapeutic options. The incidences of
      hepatocellular carcinoma (HCC) and intrahepatic cholangiocarcinoma are also
      rising, and HCC is now the leading cause of obesity-related cancer deaths in
      middle-aged men in the USA. In this Review, we summarize the correlations between
      liver cancer and NAFLD-related cirrhosis, and the role of the metabolic syndrome
      in the development of liver cancer from diverse aetiologies, including HCV
      mediated cirrhosis. Recent advances in understanding the progression of NAFLD to
      HCC from preclinical models will also be discussed. Targeted genetic manipulation
      of certain metabolic or stress-response pathways, including one-carbon
      metabolism, NF-kappaB, PTEN and microRNAs, has been valuable in elucidating the
      pathways that regulate carcinogenesis in NAFLD. Although tremendous advances have
      occurred in the identification of diagnostic and therapeutic opportunities to
      reduce the progression of NAFLD, considerable gaps in our knowledge remain with
      regard to the mechanisms by which NAFLD and its risk factors promote liver
      cancer. 

PMID- 24080780
TI  - A simple physical phantom for an intercomparison exercise on 241Am activity
      determination in the skull.
AB  - A simple hemispherical phantom has been designed and prepared for the EURADOS
      intercomparison exercise on (241)Am activity determination in the skull (2011
      13). The phantom consists of three parts that substitute bone and soft tissues.
      (241)Am is deposited on the surfaces of the bone-substituting part. The design
      and assumed composition of phantom parts are discussed. A preparation of the
      voxel representation of the phantom is described. The spectrum of a real
      measurement of the physical phantom agrees well with the simulation. The physical
      phantom, and its voxel representation, is provided to the participants of the
      intercomparison exercise. 

PMID- 24080781
TI  - Fast neutron calibration fields constructed using a proton accelerator of KIRAMS
      and spectrumweighted response of various neutron detectors.
AB  - This paper presents the dosimetric quantities, realistic neutron calibration
      fields and spectrum-weighted response (SWR) of several neutron-measuring devices
      to provide guidance to health physicists and dosimetry specialists on the proper
      selection and use of survey meters in neutron fields of varying energy spectra.
      To yield the SWR, the detector response functions of 17 neutron-measuring devices
      were numerically folded with each of the produced calibration neutron spectra
      through the in-house developed software 'K-SWR'. The detectors' response
      functions were taken from the IAEA Technical Reports Series No. 403. Eight kinds
      of calibration neutron fields with high energy and high dose rates were produced
      using a proton accelerator (MC50 cyclotron) of Korea Institute of Radiological
      and Medical Sciences (KIRAMS). The fluence-average energy (Eave) varied from 3.8
      to 16.9 MeV, and the ambient-dose-equivalent rate [H(*)(10) h(-1)] varied from
      0.99 to 16.5 mSv h(-1). 

PMID- 24080782
TI  - Evaluation of radioactivity concentrations from the Fukushima nuclear accident in
      fish products and associated risk to fish consumers.

PMID- 24080783
TI  - Tuebingen CD-25 is a sensitive tool to investigate health-related quality of life
      in Cushing's disease patients in the course of the disease.
AB  - BACKGROUND: The primary object was to investigate whether the Tuebingen CD-25
      captures changes in health-related quality of life (HRQoL) sensitively in
      Cushing's disease (CD) and to identify factors that favour postoperative HRQoL.
      METHODS: 17 CD patients were scheduled for transsphenoidal tumour removal and
      filled out the inventory before and after surgery. The mean time elapsed after
      surgery was 14.4 +/- 11.3 months. All patients were in remission at the second
      timepoint of investigation. RESULTS: HRQoL as assessed with the Tuebingen CD-25
      improved significantly after successful surgical tumour removal. A large effect
      size (Cohen's d = 0.84) in the total score indicates good sensitivity to change.
      13 patients (76.5%) showed impaired HRQoL preoperatively compared with a general
      population sample. Postoperatively, 35.3% of the patients still suffered from an
      impaired HRQoL. Stepwise linear regression analysis revealed that less
      comorbidities (<=2) and greater morning cortisol decrease were promotive factors
      for better postoperative HRQoL (p < 0.05). The postoperative improvement in HRQoL
      could be best predicted by the presence of preoperative HRQoL impairment and age
      of the patients, i.e. patients who were younger were more likely to improve.
      Moreover, patients without postoperative pituitary deficiencies improved
      significantly more in the cognition scale. A tendency towards more improvement in
      overall HRQoL was observed in non-hypocortisolaemic patients. CONCLUSIONS: The
      Tuebingen CD-25 has proved to be a capable and sensitive instrument to
      investigate HRQoL in the course of disease. The number of postoperative
      comorbidities had the greatest impact on postoperative well-being.

PMID- 24080784
TI  - Stabilization mechanism of gamma-Mg17Al12 and beta-Mg2Al3 complex metallic
      alloys.
AB  - Large-unit-cell complex metallic alloys (CMAs) frequently achieve stability by
      lowering the kinetic energy of the electron system through formation of a
      pseudogap in the electronic density of states (DOS) across the Fermi energy
      epsilonF. By employing experimental techniques that are sensitive to the
      electronic DOS in the vicinity of epsilonF, we have studied the stabilization
      mechanism of two binary CMA phases from the Al-Mg system: the gamma-Mg17Al12
      phase with 58 atoms in the unit cell and the beta-Mg2Al3 phase with 1178 atoms in
      the unit cell. Since the investigated alloys are free from transition metal
      elements, orbital hybridization effects must be small and we were able to test
      whether the alloys obey the Hume-Rothery stabilization mechanism, where a
      pseudogap in the DOS is produced by the Fermi surface-Brillouin zone
      interactions. The results have shown that the DOS of the gamma-Mg17Al12 phase
      exhibits a pronounced pseudogap centered almost exactly at epsilonF, which is
      compatible with the theoretical prediction that this phase is stabilized by the
      Hume-Rothery mechanism. The disordered cubic beta-Mg2Al3 phase is most likely
      entropically stabilized at high temperatures, whereas at lower temperatures
      stability is achieved by undergoing a structural phase transition to more ordered
      rhombohedral beta' phase at 214  degrees  C, where all atomic sites become fully
      occupied. No pseudogap in the vicinity of epsilonF was detected for the beta'
      phase on the energy scale of a few 100 meV as determined by the 'thermal
      observation window' of the Fermi-Dirac function, so that the Hume-Rothery
      stabilization mechanism is not confirmed for this compound. However, the
      existence of a much broader shallow pseudogap due to several critical reciprocal
      lattice vectors [Formula: see text] that simultaneously satisfy the Hume-Rothery
      interference condition remains the most plausible stabilization mechanism of this
      phase. At Tc = 0.85 K, the beta' phase undergoes a superconducting transition,
      which slightly increases the cohesive energy and may contribute to relative
      stability of this phase against competing neighboring phases.

PMID- 24080785
TI  - A method of evaluating helmet rotational acceleration protection using the
      Kingston Impact Simulator (KIS Unit).
AB  - OBJECTIVE: Helmet use is the primary form of head protection against traumatic
      brain injury. Although helmet designs have proven to be effective in reducing the
      incidence of skull fracture and major traumatic brain injury, there is little
      evidence that helmets protect against concussion. Linear and rotational
      accelerations are important mechanisms underlying concussion, yet current testing
      protocols do not account for rotational acceleration. Technical considerations
      have prevented a valid, accurate, and reproducible testing paradigm. Our
      objectives were to design a novel helmet-testing methodology that accurately and
      reliably measures rotational acceleration at injury-relevant impact forces,
      locations, and planes and to evaluate differences in rotational force protection
      in commercially available helmets. SETTING: Laboratory study. INTERVENTION: The
      Kingston Impact Simulator (KIS unit) was used to study 10 commercially available
      hockey helmets. The rotational acceleration force protection was measured in the
      horizontal, coronal, and sagittal planes at each of 12 predetermined impact
      locations. RESULTS: Mean peak unhelmeted and helmeted accelerations at all impact
      locations and planes ranged from 63 to 28.6 g and from 26.8 to 8.0 g,
      respectively. The percent reduction in rotational acceleration for all test
      helmets ranged from 6.4% to 84%. Statistically significant differences in
      rotational acceleration between manufacturers and within a helmet brand were
      identified. CONCLUSIONS: KIS is a novel testing methodology that identifies
      rotation force protection within and between hockey helmet models and
      manufacturers at different impact location and planes. This information may be
      useful in improving future helmet design and construction to provide maximal
      protection against the forces causing concussion.

PMID- 24080786
TI  - Residual mechanical effectiveness of external ankle tape before and after
      competitive professional soccer performance.
AB  - OBJECTIVE: To evaluate the presupposed preventive residual mechanical
      effectiveness of the widespread use of adhesive elastic ankle tape after a
      nonlaboratory, realistic soccer-specific outfield intervention reflecting a
      soccer halftime. DESIGN: A prospective nonrandomized test-retest design was used.
      SETTING: Laboratory. PARTICIPANTS: Seventeen professional male outfield players
      (mean age, 25.5) without any signs of chronic ankle instability. INTERVENTION:
      Participants were investigated before and after a 45-minute soccer-specific field
      intervention. MAIN OUTCOME MEASURES: The passive inversion range of motion (ROM)
      of the ankle was tested unloaded on a self-developed inversion device with and
      without a standardized ankle tape before and after the intervention.
      Additionally, electromyography signal was taken to assure the inactivity of the
      protective evertor muscles, and reliability tests for the inversion device (test
      retest and trial to trial) were conducted in 12 healthy controls. RESULTS: Tape
      restricted the maximum passive inversion ROM of the uninjured ankle significantly
      to 50.3%. The protection declined nearly completely after 45 minutes of outfield
      soccer performance to a negligible nonsignificant ROM restriction of 9.7%.
      Pearson correlation coefficient for the reliability was 0.931 (P <= 0.001) for
      the test-retest and 0.983 (P <= 0.001) for the trial-to-trial test. CONCLUSIONS:
      The initial significant protection of external ankle-tape support declines almost
      completely without relevant remaining residual mechanical effect after 45
      minutes, reflecting a soccer halftime. The so far presupposed residual mechanical
      effectiveness of tape to prevent injury is increasingly irrelevant during soccer
      performance and consequently antidromic to the increasing injury risk toward the
      end of a soccer halftime.

PMID- 24080787
TI  - Influence of life-style choices on locomotor disability, arthritis and
      cardiovascular disease in older women: prospective cohort study.
AB  - BACKGROUND: many chronic conditions have their roots in modifiable health-related
      behaviours. METHODS: a total of 4,286 women aged 60-79 in the British Women's
      Heart and Health Study are followed up for incident cardiovascular disease (CVD),
      arthritis and locomotor disability over 7 years. Self-reported smoking, alcohol
      consumption, exercise and fruit intake at baseline is also available.
      Associations between these and each outcome, plus a composite outcome, are
      investigated in those without prevalent disease at baseline using logistic
      regression with multiple imputation. RESULTS: ex-smokers and current smokers
      showed increased odds of locomotor disability, CVD and the combined outcome. Less
      regular exercisers had increased odds of all outcomes, particularly locomotor
      disability. There was no evidence that alcohol or fruit intake was associated
      with any outcome. Population attributable fractions (PAFs) suggest in addition to
      the influence of smoking and alcohol, exercise accounts for 9% of incident
      locomotor disability, 5% of CVD and 4% of arthritis. All four lifestyle factors
      combined account for 17% of incident locomotor disability and 9% of incident
      conditions combined. CONCLUSIONS: never smokers and regular exercisers had
      substantially reduced odds of 7-year disability onset. Low PAFs suggest changes
      in health-related behaviours in older women would result in only modest
      reductions in common chronic conditions.

PMID- 24080788
TI  - Expanding the chemistry of fluorescent protein biosensors through genetic
      incorporation of unnatural amino acids.
AB  - Fluorescent proteins are essential tools in biological research, ranging from the
      study of individual biological components to the interrogation of complex
      cellular systems. Fluorescent protein derived biosensors are increasingly applied
      to the study of biological molecules and events in living cells. The present
      review focuses on a specific class of fluorescent protein biosensors in which a
      genetically installed unnatural amino acid (UAA*) acts as the sensing element.
      Upon direct interaction with the analyte of interest, the chemical and/or
      physical properties of UAA* are altered, which triggers fluorescence property
      changes of the biosensor and generates readouts. In comparison to mutagenesis
      approaches within the standard genetic code, introduction of UAA*s with a unique
      functionality and chemical reactivity could broaden the scope of analytes and
      improve the specificity of biosensors. Nonconventional functional groups in
      fluorescent proteins enable sensor designs that are not readily accessible using
      the common twenty amino acids. Recent reports of UAA*-containing fluorescent
      protein sensors serve as excellent examples for the utility of such sensor
      design. We envisage that the integration of the two powerful chemical biology
      tools, fluorescent protein sensors and genetic incorporation of UAA*s, will lead
      to novel biosensors that can expand and deepen current understanding of cellular
      processes. 

PMID- 24080789
TI  - Thirteen-year vitreoretinal surgical outcomes of 5,097 cases from a tertiary
      referral center in Turkey.
AB  - A 13-year retrospective chart review of 5,097 consecutive cases that underwent
      pars plana vitrectomy (PPV) in a tertiary referral center in Turkey was
      performed. Age at onset, sex, laterality, associated systemic disease, pre- and
      postoperative visual acuities (VA), indications, type of surgery and outcomes of
      surgery were analyzed. The most common indications for vitreoretinal surgery
      (VRS) were rhegmatogenous retinal detachment (n = 1,802, 35.4%) and proliferative
      diabetic retinopathy (n = 1,505, 29.5%). The most common vitreoretinal technique
      combinations performed were PPV with encircling endolaser (EL) and
      phacoemulsification with intraocular lens implantation (33.0%), PPV with
      encircling EL (30.4%), and only PPV (7.0%). A statistically significant increase
      in the mean VA was noted at the first- (1.16 +/- 0.44 logarithm of the minimum
      angle of resolution, logMAR) and sixth-month (1.06 +/- 0.61 logMAR) visits when
      compared to the preoperative VA (1.77 +/- 0.58 logMAR; p < 0.001). Comparisons in
      the top surgical indications, techniques and outcomes for vitrectomy between the
      countries could be important for the development of subspecialization in VRS.

PMID- 24080790
TI  - Flagellate erythema in a patient with fever.

PMID- 24080791
TI  - Photoresponsive quinoline tethered fluorescent carbon dots for regulated
      anticancer drug delivery.
AB  - A photoresponsive nano drug delivery system (DDS) was constructed using two new
      ingredients: fluorescent carbon dots and a quinoline based phototrigger. The
      strong fluorescent properties of carbon dots have been explored for in vitro
      cellular imaging application, and the phototrigger ability of quinoline was
      exploited for efficient anticancer drug release using both one-photon and two
      photon excitation. 

PMID- 24080792
TI  - Risk factors of gamma-hydroxybutyrate overdosing.
AB  - The aim of this study was to identify in recreational drug users the factors
      which increase the risk of overdosing (OD) with gamma-hydroxybutyrate (GHB). A
      purposive sample of 45 experienced GHB users was interviewed, equally divided
      into three groups (never OD, occasional OD, and repeat OD). The repeat OD group
      scored highest on many risk factors regarding GHB use, the occasional OD group
      scored intermediate, and the never OD group scored lowest. Participants, whether
      or not they had overdosed on GHB, most often perceived GHB use (e.g. using more
      GHB than usual, using GHB doses too closely together) as the main reason for GHB
      OD, and many participants who had overdosed on GHB reported that they had taken
      more GHB than usual at their most recent occasion of GHB OD. No significant
      differences in co-use of GHB with other substances were found between the three
      groups. Our findings indicate that using GHB in the company of groups of friends
      probably reduces, but does not eliminate, the risk of OD.

PMID- 24080793
TI  - How do changes in body mass index in infancy and childhood associate with
      cardiometabolic profile in adulthood? Findings from the Northern Finland Birth
      Cohort 1966 Study.
AB  - BACKGROUND/OBJECTIVE: Postnatal growth patterns leading to obesity may have
      adverse influences on future cardiometabolic health. This study evaluated age and
      body mass index (BMI) at infant BMI peak (BMIP) and childhood BMI rebound (BMIR)
      in relation to adult cardiometabolic outcomes in the Northern Finland Birth
      Cohort 1966. METHODS: BMI at various ages was calculated from frequent height and
      weight measurements obtained from child health and welfare clinical records. Age
      and BMI at BMIP and BMIR were derived from random effect models fitted at >0-1.5
      years (N=3 265) and >1.5-13 years (N=4 121). Cardiometabolic outcomes were
      obtained from a clinical examination at age 31 years. Multiple regression models
      were used to analyse associations between the derived growth parameters and
      cardiometabolic outcomes. RESULTS: Age and BMI at BMIP were positively associated
      with adult BMI and waist circumference (WC), independently of birth weight and
      infant height growth (P<0.05). Later BMIR was associated with a better
      cardiometabolic profile: adult BMI and insulin were 14% lower, WC and
      triglycerides were 10% lower and the odds of metabolic syndrome (MetS) were 74%
      lower per 2 s.d. (1.86 years) higher age at BMIR (P<0.0001). BMI at rebound had
      generally weaker associations with cardiometabolic outcomes, which attenuated
      after adjustment for age at BMIR. CONCLUSIONS: Age and BMI at infant BMIP were
      associated with adult adiposity but not with other cardiometabolic outcomes.
      Earlier timing of BMIR was a risk factor of an adverse cardiometabolic profile,
      independently of early growth or BMI at rebound. Identifying growth patterns
      harmful to cardiovascular health will give opportunities for early interventions.

PMID- 24080794
TI  - Diet-induced obesity may affect the uterine immune environment in early-mid
      pregnancy, reducing NK-cell activity and potentially compromising uterine
      vascularization.
AB  - OBJECTIVES: To investigate the effect of obesity in early-mid pregnancy on
      crucial pregnancy hormones and the uterine immune environment. BACKGROUND:
      Obesity impacts reproductive ability, adversely affecting conception and leading
      to complications in pregnancy. Obesity is often regarded as a stress state and an
      immune disease, both of which may contribute to pregnancy failure. We previously
      demonstrated that stress in early pregnancy greatly alters progesterone
      secretion. As progesterone is an immunomodulator, altered progesterone secretion
      may adversely modify the maternal immune system. In the current study, we test
      the hypothesis that obesity during pregnancy adversely alters the uterine immune
      environment. METHODS: An obese mouse model was created by feeding C57/BL6 mice on
      a high-fat (HF)/sugar diet for 12 weeks before pregnancy. Control mice were fed
      on lower-fat/sugar chow. Mice were mated, and on day 7.5 of pregnancy plasma
      progesterone and prolactin were measured by immunoassay. Cells from the uterus
      draining inguinal lymph nodes were collected for analysis of the uterine immune
      response by flow cytometry. RESULTS: Diet-induced obesity increased the secretion
      of progesterone and altered a number of uterine natural killer (NK)- and T-cell
      responses. These included a marked reduction in the percentage of leucocyte
      derived NK cells and reduced expression of interferon-gamma (IFN-gamma) in the NK
      cells compared with control mice. CONCLUSIONS: Maternal obesity, induced by an HF
      diet, may lead to a reduction in the expression of IFN-gamma in NK cells. NK-cell
      derived IFN-gamma is reported to be involved in supporting uterine spiral artery
      remodelling. Thus, obesity in early pregnancy may compromise vascularization by
      reducing the expression of IFN-gamma-positive NK cells. Furthermore, the
      expression of uterine CD8(+) cells was reduced in the HF diet-fed mice,
      suggesting obesity may adversely alter the maternal immune adaptation that is
      essential for effective pregnancy.

PMID- 24080795
TI  - Dialysis: low-glucose-containing peritoneal dialysis solutions: good or bad?
AB  - Two trials of low-glucose-containing peritoneal dialysis regimen in patients with
      diabetes mellitus show that although this strategy improved glycaemic control, it
      was associated with increased risk of serious adverse events and mortality. These
      studies suggest caution is needed when evaluating effectiveness using surrogate
      measures and awareness of confounding factors is important.

PMID- 24080796
TI  - Transplantation: a new molecular approach to the diagnosis of acute rejection.
AB  - Renal biopsy is the gold standard for detection of rejection in kidney transplant
      recipients, but is not considered until evidence of renal dysfunction is
      apparent. Now, Suthanthiran and colleagues suggest that mRNA levels in urinary
      cells from these patients might be diagnostic and prognostic of acute cellular
      rejection.

PMID- 24080797
TI  - Acute kidney injury: novel protective role of H-Ferritin.

PMID- 24080798
TI  - Chronic kidney disease: after nephron reduction, podoctyes get in on the AKT.

PMID- 24080799
TI  - Chronic kidney disease: optimal blood pressure for kidney disease-lower is not
      better.
AB  - Current guidelines recommend lowering blood pressure (BP) in patients with
      chronic kidney disease and hypertension. However, a new study suggests that
      achieving ideal systolic BP targets at the expense of low diastolic BP <70 mmHg
      is not advantageous for outcomes.

PMID- 24080801
TI  - Vasculitis syndromes: RAVE about rituximab in ANCA vasculitis?
AB  - Follow-up data from the RAVE trial have shown that rituximab is as effective as
      immunosuppression with cyclophosphamide followed by azathioprine in
      antineutrophil cytoplasmic antibody (ANCA) associated vasculitis. Rituximab is
      likely to become the standard of care for many patients with ANCA disease.
      However, an individualized approach is needed to identify those who require more
      intense or prolonged therapy.

PMID- 24080804
TI  - Slings in the management of male stress urinary incontinence.
AB  - PURPOSE OF REVIEW: The use of synthetic slings for the treatment of male stress
      urinary incontinence (SUI) has increased over the last decade. Several sling
      designs and techniques are now available. The purpose of this review is to
      summarize the past literature with a focus on more recent contributions. RECENT
      FINDINGS: The recent literature focusses on the retrourethral transobturator
      sling (RTS), which is considered noncompressive. MRI of patients undergoing RTS
      has shown an increase in membranous urethral length and elevation of the external
      urethral sphincter, whereas a recent large series demonstrated approximately a
      half and a quarter of patients are cured or improved, respectively, at 1 year
      after RTS implantation, with results sustained through to 3 years. Serious
      complications such as urethral erosion occur rarely. SUMMARY: The available
      evidence suggests that male slings can be an efficacious and well tolerated
      treatment modality for men with SUI. Nevertheless, important questions remain
      with regard to the durability of repair, device safety and comparative efficacy.
      The mechanism of action and factors that predict failure remain to be fully
      elucidated.

PMID- 24080803
TI  - Gonadotropin-releasing hormone neurones innervate kisspeptin neurones in the
      female mouse brain.
AB  - Kisspeptin (KP) neurones in the rostral periventricular area of the third
      ventricle (RP3V) and arcuate nucleus (Arc) are important elements in the neuronal
      circuitry regulating gonadotropin-releasing hormone (GnRH) secretion. KP and co
      synthesised neuropeptides/neurotransmitters act directly on GnRH perikarya and
      processes. GnRH neurones not only form the final output pathway regulating the
      reproductive functions of the anterior pituitary gland, but also provide neuronal
      input to sites within the hypothalamus. The current double-label
      immunohistochemical studies investigated whether GnRH-immunoreactive (IR)
      projections to the RP3V and/or Arc establish morphological connections with KP-IR
      neurones at these sites. To optimise visualisation of KP immunoreactivity in,
      respectively, the RP3V and Arc, ovariectomised (OVX) oestrogen-treated and OVX
      oil-treated female mice were studied. Confocal laser microscopic analysis of
      immunofluorescent specimens revealed GnRH-IR axon varicosities in apposition to
      approximately 25% of the KP-IR neurones in the RP3V and 50% of the KP-IR neurones
      in the Arc. At the ultrastructural level, GnRH-IR neurones were seen to establish
      asymmetric synaptic contacts, which usually reflect excitatory neurotransmission,
      with KP-IR neurones in both the RP3V and Arc. Together with previous data, these
      findings indicate reciprocal connectivity between both of the KP cell populations
      and the GnRH neuronal system. The functional significance of the GnRH-IR input to
      the two separate KP cell populations requires electrophysiological investigation.

PMID- 24080802
TI  - The role of the glomerular endothelium in albumin handling.
AB  - The unique permeability characteristics of the glomerular capillary wall depend
      on its three-layer structure, consisting of endothelial cells, the basement
      membrane and podocytes. These components form the glomerular filtration barrier
      (GFB). That albuminuria may occur in the absence of changes in podocyte foot
      processes suggests that GFB components other than podocytes have essential roles
      in albumin handling. The endothelium forms the first part of the GFB and is
      characterized by fenestrations-transcellular holes that are filled with
      endothelial glycocalyx, a hydrated mesh principally comprised of proteoglycans.
      The glycocalyx and adsorbed plasma constituents form the endothelial surface
      layer (ESL). Human and animal studies have shown that the glomerular ESL
      restricts macromolecule passage and ensures that plasma albumin is largely
      excluded from the GFB. The glomerular endothelium is also likely to indirectly
      influence glomerular albumin handling by modifying podocyte behaviour. These
      modifications may occur physiologically through soluble mediators and/or
      pathologically through increased exposure of podocytes to plasma components as a
      consequence of ESL dysfunction. The importance of the glomerular endothelium and
      ESL in albumin handling also sheds light on the relationship between albuminuria
      and vascular disease. The therapeutic potential that this relationship offers
      will become evident with better understanding of the structure, composition and
      regulation of the glycocalyx.

PMID- 24080805
TI  - Clinical phenotyping of urologic pain patients.
AB  - PURPOSE OF REVIEW: Urologic pain conditions such as chronic prostatitis/chronic
      pelvic pain syndrome, interstitial cystitis/bladder pain syndrome and chronic
      orchialgia are common, yet diagnosis and treatment are challenging. Current
      therapies often fail to show efficacy in randomized controlled studies. Lack of
      efficacy may be due to multifactorial causes and heterogeneity of patient
      presentation. Efforts have been made to map different phenotypes in patients with
      urologic pain conditions to tailor more effective therapies. This review will
      look at current literature on phenotype classification in urologic pain patients
      and their use in providing effective therapy. RECENT FINDINGS: There has been
      validation of the 'UPOINT' system (urinary symptoms, psychosocial dysfunction,
      organ specific findings, infection, neurologic/systemic and tenderness of muscle)
      to better categorize male chronic prostatitis/chronic pelvic pain syndrome and
      interstitial cystitis/bladder pain syndrome. Refinement of domain systems and
      recent cluster analysis has suggested possible central processes involved in
      urologic pain conditions similar to systemic pain syndromes such as fibromyalgia,
      chronic fatigue and irritable bowel syndrome. SUMMARY: Domain characterization of
      urologic pain conditions via phenotype mapping can be used to better understand
      causes of chronic pain and hopefully provide more effective, targeted and
      multimodal therapy.

PMID- 24080807
TI  - New developments in the diagnosis and treatment of chronic prostatitis/chronic
      pelvic pain syndrome.
AB  - PURPOSE OF REVIEW: To describe new developments in the diagnosis and treatment of
      chronic prostatitis/chronic pelvic pain syndrome (CPPS). RECENT FINDINGS:
      Symptoms in men with chronic prostatitis/CPPS appear to cluster into a group with
      primarily pelvic or localized disease, and a group with more systemic symptoms.
      Several other chronic pain conditions can be associated with chronic
      prostatitis/CPPS, including irritable bowel syndrome, fibromyalgia, and chronic
      fatigue syndrome. Markers of neurologic inflammation and autoimmune disease
      parallel changes in symptoms after treatment. Treatment options include new alpha
      blockers, psychological intervention, and prostate-directed therapy. The areas of
      acupuncture and pelvic floor physical therapy/myofascial release have received
      increased recent attention and appear to be good options in these patients.
      Future therapy may include antibodies to mediators of neurogenic inflammation and
      even treatment of bacteria in the bowel. SUMMARY: The diagnosis of chronic
      prostatitis/CPPS must include conditions traditionally outside the scope of
      urologic practice but important for the care of men with chronic pelvic pain. The
      treatment is best done using multiple simultaneous therapies aimed at the
      different aspects of the condition.

PMID- 24080806
TI  - The importance of psychological assessment in chronic pain.
AB  - PURPOSE OF REVIEW: Much confusion has surrounded the purpose of the psychological
      assessment in the context of chronic pain. For many clinicians, the psychological
      assessment is used to rule out psychiatric illness and to identify the nonmedical
      causes for pain and disability. In essence, it is used to identify the causes of
      pain that fall outside of the biomedical model. Supported by over 30 years of
      evidence, the bio-psycho-social model acknowledges that psychosocial factors are
      inherent in chronic pain and require assessment if meaningful diagnostics and
      treatments are to occur. RECENT FINDINGS: Five broad categories of psychosocial
      assessment are relevant to chronic pain. These categories have been shown to
      enhance the diagnosis of the underlying forms of pain, predict the transition
      from acute to chronic status, and help to phenotype individuals for the discovery
      of the underlying mechanisms responsible for pain. SUMMARY: Informed assessment
      of chronic pain needs to include relevant biological, psychological, and social
      domains. This article describes those domains and offers suggestions of specific
      instruments to use in clinical or research settings.

PMID- 24080808
TI  - A contemporary update on the management of male incontinence.

PMID- 24080809
TI  - Afferent neurourology and urologic pain syndromes: current state of the art.

PMID- 24080810
TI  - Male incontinence: onabotulinum toxin A and sacral nerve stimulation.
AB  - PURPOSE OF REVIEW: Overactive bladder affects 10-12% of men, of which 13% are
      refractory to medical therapy and seek second-line treatment. This places a
      substantial clinical and economic burden on the National Health Service United
      Kingdom. RECENT FINDINGS: This review identifies current evidence for the use of
      onabotulinum toxin A and sacral nerve neuromodulation for the treatment of
      overactive bladder in patients who do not respond to optimal medical treatment.
      Posterior tibial nerve stimulation is not covered here. Clinical and financial
      implications of the treatments are reviewed. SUMMARY: The focus will remain on
      recently published evidence, which may be useful to clinicians managing
      refractory patients.

PMID- 24080811
TI  - Artificial sphincter.
AB  - PURPOSE OF REVIEW: This review examines the evidence to date, and summarizes the
      indications, technical and surgical aspects, risk factors and challenges of peer
      reviewed artificial sphincters in the treatment of male stress urinary
      incontinence (SUI). RECENT FINDINGS: Although new devices have been introduced,
      the AMS 800 continues to be the most implanted and reported on artificial urinary
      sphincter (AUS) worldwide. Although the AUS seems to be effective in the
      treatment of neurogenic and non-neurogenic SUI, large randomized, controlled
      trials are missing. Urethral erosion, atrophy and infection are the primary
      reported risk factors for high revision rates with most surgeons performing less
      than three implants per year. Transurethral catheterization has been identified
      as the main risk factor for urethral erosion. Surgical modifications have been
      reported with good outcomes. The perineal implantation of a single cuff continues
      to be the most frequently used procedure, but transcorporal implantation may be
      helpful in salvage situations. Recent device improvements, such as the antibiotic
      coating, do not seem to influence infection rates. New devices continued to be
      introduced; however, short-term and long-term results in larger studies are
      required. Patients with concomitant SUI and erectile dysfunction have the option
      of a synchronous implantation with an AUS and penile prosthesis with similar
      results. SUMMARY: Despite the low level of evidence, the AUS is well tolerated,
      effective and recommended for male SUI treatment in urological guidelines.
      Implantation in high-volume experienced centers is strongly recommended.
      Comprehensive patient counselling is required to prevent complications and
      necessary revisions.

PMID- 24080812
TI  - Update in management of male urinary incontinence: injectables, balloons,
      minimally invasive approaches.
AB  - PURPOSE OF REVIEW: The surgical armamentarium for stress urinary incontinence in
      men ranges from minimally invasive endoscopic procedures to artificial urinary
      sphincter implantation. In this rapidly moving field, respective indications of
      surgical options are also evolving, as evidence for the use of innovative devices
      is growing. This review is focused on recent data about injectables, stem cells
      and periurethral balloons implantation. RECENT FINDINGS: Periurethral injections
      are probably the most minimally invasive options, but are considered of low
      efficacy, with a high recurrence rate in the short term. Reinjections are often
      needed. However, the market share of periurethral bulking is decreasing
      relatively slowly. Innovative, so-called regenerative therapies, including
      injection of biological material, stem cells, myoblasts and muscle strings
      implantation have shown promising results but did not yet reach maturity for
      daily use in the clinic. Periurethral balloons implantation shows an acceptable
      success rate at mid-term follow-up, but are associated with a high rate of
      complications and reoperations. SUMMARY: Indications of periurethral bulking are
      decreasing. Regenerative therapies are still under investigation in men, and long
      term studies are still required. Comparative studies against male slings and
      other compression devices are still awaited to accurately determine the role of
      periurethral balloons implantation.

PMID- 24080813
TI  - Diagnosis of male incontinence.
AB  - PURPOSE OF REVIEW: A review of the diagnosis of male urinary incontinence, with
      particular reference to studies published within the last year. RECENT FINDINGS:
      One of the most important studies from the last year is the drafting of a bladder
      diary, consistent with the International Consultation on Incontinence modular
      Questionnaire modules. Patients and clinicians have been consulted on content and
      format, and further phases are intended to test validity and reliability of the
      diary. SUMMARY: Initial assessment of men with incontinence involves a focussed
      history, examination and simple investigations. It is imperative to accurately
      define terminology of lower urinary tract symptoms. Questionnaires and bladder
      diaries are important adjuncts. Further urodynamic assessment may also aid
      diagnosis, particularly in situations where surgery is contemplated.

PMID- 24080814
TI  - Combatting the obesity epidemic in rural America: a few considerations.

PMID- 24080815
TI  - Stakeholder perceptions of obesity-prevention strategies: a comparison of
      geographically diverse rural counties.
AB  - Understanding barriers and facilitators to strategies directed at obesity
      prevention policy change, particularly in rural, southern US counties where
      obesity is more prevalent, is important so that strategies deemed most winnable
      can be pursued. As such, community stakeholders and policy makers were
      interviewed using the Centers for Disease Control and Prevention's Common
      Community Measures for Obesity Prevention Assessment in 2 rural, geographically
      diverse regions of North Carolina. Stakeholder interviews revealed many
      similarities despite population differences and unique geographic challenges to
      each region. In both Western and Eastern North Carolina, strategies involving
      increasing opportunities for physical activity were deemed the most winnable,
      whereas strategies incentivizing businesses to locate in underserved areas and
      limiting advertisements of unhealthy food and beverages were deemed the least
      winnable. Differences among Western and Eastern North Carolina regions revolved
      around zoning, geographic constraints, and topographically influenced local food
      strategies. These findings add to the literature by systemically identifying
      similarities and differences among geographically diverse rural communities. 

PMID- 24080816
TI  - "Health in All Policies": taking stock of emerging practices to incorporate
      health in decision making in the United States.
AB  - OBJECTIVE: Policies affecting the determinants of health lie largely outside the
      control of the health care and public health sectors. Ensuring health
      considerations in the formation and implementation of policies, programs,
      projects, and plans from all sectors, though lofty, is the overall aim of Health
      in All Policies. The purpose of this article was to identify categories of
      strategies that illustrate how Health in All Policies had been implemented in the
      United States. DESIGN: We used a 3-phased process: (1) review of the published
      and gray literature; (2) analysis of case examples to identify a draft framework,
      which included tactics and strategies for implementing Health in All Policies;
      and (3) vetting the draft framework through individual and group consultation.
      RESULTS: We identify 7 interrelated strategies for incorporating health
      considerations into decisions and systems: (1) developing and structuring cross
      sector relationships; (2) incorporating health into decision-making processes;
      (3) enhancing workforce capacity; (4) coordinating funding and investments; (5)
      integrating research, evaluation and data systems; (6) synchronizing
      communications and messaging; and (7) implementing accountability structures. For
      each strategy, we provide illustrative examples from the United States to help
      public health leaders identify effective tactics for Health in All Policies
      implementation. CONCLUSIONS: Through our review, we offer a starting point for
      categorizing and describing the emerging practices used to work across sectors
      and address the determinants of health. By delineating the different types of
      strategies and tactics to achieve Health in All Policies, we provide public
      health practitioners with a "menu" of options for incorporating Health in All
      Policies into their work.

PMID- 24080817
TI  - Successful physician transformation strategies for the new health system
      environment.

PMID- 24080818
TI  - Obesity as disease: an opportunity for integrating public health and clinical
      medicine.

PMID- 24080819
TI  - Examination of local health department capacity and infrastructure for injury and
      violence prevention.

PMID- 24080820
TI  - Social network analysis: a novel approach to legal research on emergency public
      health systems.

PMID- 24080821
TI  - The inside-out amyloid hypothesis and synapse pathology in Alzheimer's disease.
AB  - Cumulative evidence in brains and cultured neurons of Alzheimer's disease (AD)
      transgenic mouse models, as well as in human postmortem AD brains, highlights
      that age-related increases in beta-amyloid peptide (Abeta), particularly in
      endosomes near synapses, are involved in early synapse dysfunction. Our
      immunoelectron microscopy and high-resolution immunofluorescence microscopy
      studies show that this early subcellular Abeta accumulation leads to progressive
      Abeta aggregation and pathology, particularly within dystrophic neurites and
      synapses. These studies confirm that neuritic/synaptic Abeta accumulation is the
      nidus of plaque formation. Abeta-dependent synapse pathology in AD models is
      modulated by synaptic activity and is plaque independent. The amyloid precursor
      protein (APP) is normally transported down neurites and appears to be
      preferentially processed to Abeta at synapses. Synapses are sites of early Abeta
      accumulation and aberrant tau phosphorylation in AD, which alter the synaptic
      composition at early stages of the disease. Elucidating the normal role of APP,
      and potentially of Abeta, at synapses should provide important insights into the
      mechanism(s) of Abeta-induced synapse dysfunction in AD and how to
      therapeutically mitigate these dysfunctions.

PMID- 24080824
TI  - Bone marrow-derived mononuclear cells promote improvement in glomerular function
      in rats with early diabetic nephropathy.
AB  - BACKGROUND/AIMS: Diabetic nephropathy is one of the main causes of end-stage
      renal disease. The present study investigated the effect of mononuclear cell (MC)
      therapy in rats subjected to diabetic nephropathy. METHODS: Male Wistar rats were
      divided into control (CTRL), diabetic (DM), CTRL+MC and DM+MC groups. Diabetes
      was induced by a single injection of streptozotocin (45 mg/kg, i.p.) and, 4 weeks
      later, 2*10(7) MCs were injected via the jugular vein. RESULTS: The rats in the
      DM and DM+MC groups showed increased glycemia, glomerular filtration rate and
      glomerular tuff area versus control groups. The glomerular filtration rate and
      glomerular tuff area were normalized in the DM+MC group. No alterations were
      observed in the fractional excretion of electrolytes and proteinuria between the
      DM and DM+MC groups. TGF-beta1 protein levels in the DM group were significantly
      increased versus control animals and normalized in the DM+MC group. An increase
      in ED1(+)/arginase I(+) macrophages and IL-10 renal expression was observed in
      the DM+MC group versus DM group. CONCLUSIONS: Bone marrow-derived MC therapy was
      able to prevent glomerular alterations and TGF-beta1 protein overexpression and
      modulated glomerular arginase I(+) macrophage infiltration in rats subjected to
      early diabetic nephropathy.

PMID- 24080823
TI  - AMPKalpha1-sensitivity of Orai1 and Ca(2+) entry in T - lymphocytes.
AB  - BACKGROUND/AIMS: T-lymphocyte activation and function critically depends on
      Ca(2+) signaling, which is regulated by store operated Ca(2+) entry (SOCE). Human
      and mouse T lymphocytes express AMP activated kinase AMPKalpha1, which is rapidly
      activated following elevation of cytosolic Ca(2+) concentration ([Ca(2+)]i) by
      treatment of the cells with Ca(2+) ionophore or following inhibition of endosomal
      Ca(2+) ATPase with thapsigargin. AMPK is further activated by triggering of the T
      cell antigen receptor (TCR). The present study explored whether AMPK influences
      Ca(2+) entry and Ca(2+)-sensitive regulation of T-lymphocyte function. METHODS: T
      lymphocytes were isolated and cultured from AMPKalpha1-deficient (ampk(-/-)) mice
      and from their wildtype (ampk(+/+)) littermates. The phenotype of the cells was
      analysed by flow cytometry, [Ca(2+)]i estimated from Fura-2 fluorescence, SOCE
      from increase of [Ca(2+)]i following thapsigargin treatment (1 uM), and cell
      function analysed by measuring cytokine secretion and western blotting. RESULTS:
      Expression of surface markers in CD4(+) and CD8(+) T-cells were similar in ampk(
      /-) and ampk(+/+) T-lymphocyte blasts. Moreover, total STIM1 protein abundance
      was similar in ampk(-/-) and ampk(+/+) T-lymphocyte blasts. However, Orai1 cell
      membrane protein abundance was significantly higher in ampk(-/-) than in
      ampk(+/+) T-lymphocyte blasts. SOCE and increase of [Ca(2+)]i following TCR
      activation by triggering TCR with anti-CD3 and cross-linking secondary antibody
      were both significantly more pronounced in ampk(-/-) than in ampk(+/+) T
      lymphocyte blasts. The difference of Ca(2+) entry between ampk(-/-) and ampk(+/+)
      T-lymphocytes was abrogated by Orai1 inhibitor 2-aminoethoxydiphenyl borate (2
      APB, 50 uM). Proliferation of unstimulated ampk(-/-) lymphocytes was higher than
      proliferation of ampk(+/+) T-lymphocytes, a difference reversed by Orai1
      silencing. CONCLUSIONS: AMPK downregulates Orai1 and thus SOCE in T-lymphocytes
      and thus participates in negative feed-back regulation of cytosolic Ca(2+)
      activity.

PMID- 24080825
TI  - Relative quantitative comparison between lipotoxicity and glucotoxicity affecting
      the PARP-NAD-SIRT1 pathway in hepatocytes.
AB  - BACKGROUND/AIMS: Insulin resistance in type 2 diabetes results from a combination
      of hyperglycemia and elevated free fatty acid (FFA) concentrations. However, the
      individual effects of glucotoxicity and lipotoxicity on cell function have not
      been determined. METHODS: To compare the effects of increased FFAs and glucose
      levels on the PARP-NAD-SIRT1 pathway, which modulates insulin sensitivity, we
      cultured HepG2 hepatocytes with 300 or 500 uM oleic acid (OA) or 30 mM glucose
      for 1-4 days. PARP activity, NAD level, SIRT1 expression and insulin receptor
      phosphorylation were determined. RESULTS: PARP activity was higher while NAD
      level and SIRT1 expression were lower in OA-treated cells than in control cells.
      Insulin receptor phosphorylation in response to insulin stimulation was
      attenuated under OA stimulation. Compared to glucose, OA produced a more rapid
      effect on the PARP-NAD-SIRT1 pathway in HepG2 cells. The reduction in SIRT1
      expression and insulin receptor phosphorylation was similar in cells treated with
      500 MUM OA for 1 day and those treated with 30 mM glucose for 4 days. In addition
      to PARP activation, the LXRalpha activator T0901317 also affected SIRT1
      expression. CONCLUSION: FFAs modulated cellular function through multiple ways,
      and induced more rapid and more potent cytotoxicity than glucose.

PMID- 24080826
TI  - Chorein sensitivity of actin polymerization, cell shape and mechanical stiffness
      of vascular endothelial cells.
AB  - BACKGROUND/AIMS: Endothelial cell stiffness plays a key role in endothelium
      dependent control of vascular tone and arterial blood pressure. Actin
      polymerization and distribution of microfilaments is essential for mechanical
      cell stiffness. Chorein, a protein encoded by the VPS13A gene, defective in
      chorea-acanthocytosis (ChAc), is involved in neuronal cell survival as well as
      cortical actin polymerization of erythrocytes and blood platelets. Chorein is
      expressed in a wide variety of further cells, yet nothing is known about the
      impact of chorein on cells other than neurons, erythrocytes and platelets. The
      present study explored whether chorein is expressed in human umbilical vein
      endothelial cells (HUVECs) and addressed the putative role of chorein in the
      regulation of cytoskeletal architecture, stiffness and survival of those cells.
      METHODS: In HUVECs with or without silencing of the VPS13A gene, VPS13A mRNA
      expression was determined utilizing quantitative RT-PCR, cytoskeletal
      organization visualized by confocal microscopy, G/F actin ratio and
      phosphorylation status of focal adhesion kinase quantified by western blotting,
      cell death determined by flow cytometry, mechanical properties studied by atomic
      force microscopy (AFM) and cell morphology analysed by scanning ion conductance
      microscopy (SICM). RESULTS: VPS13A mRNA expression was detectable in HUVECs.
      Silencing of the VPS13A gene attenuated the filamentous actin network, decreased
      the ratio of soluble G-actin over filamentous F-actin, reduced cell stiffness and
      changed cell morphology as compared to HUVECs silenced with negative control
      siRNA. These effects were paralleled by a significant decrease in FAK
      phosphorylation following VPS13A silencing. Moreover, silencing of the VPS13A
      gene increased caspase 3 activity and induced necrosis in HUVECs. CONCLUSIONS:
      Chorein is a novel regulator of cytoskeletal architecture, cell shape, mechanical
      stiffness and survival of vascular endothelial cells.

PMID- 24080827
TI  - ER stress activating ATF4/CHOP-TNF-alpha signaling pathway contributes to alcohol
      induced disruption of osteogenic lineage of multipotential mesenchymal stem cell.
AB  - BACKGROUND/AIMS: Studies have provided substantial evidence that osteoblasts and
      adipocytes share common progenitor-multipotential mesenchymal stem cells in bone
      marrow (BMSCs), and excessive alcohol consumption shifts away from osteogenic to
      adipogenic lineage. However, how exactly alcohol impairs osteogenesis is still
      incompletely understood. This study was designed to shed light on this issue.
      METHODS: We treated primary BMSCs from human subjects with alcohol for 24 days.
      We measured changes of genes related to endoplasmic reticulum (ER) stress,
      adipogenic markers and osteogenic markers using quantitative real-time RT-PCR and
      Western blot analysis. We performed Oil red O staining and quantification of
      adipogenesis. We also conducted caspase 3 activity assay to assess BMSC
      apoptosis. RESULTS: We showed here that chronic exposure of BMSCs to alcohol
      induced adipogenesis and disrupted osteogenesis as indicated by upregulation of
      adipogenic markers (PPARgamma2 and aP2), downregulation of osteogenic markers
      (Osf2/Cbfa1), and accumulation of lipid droplets. Alcohol induced ER stress, as
      reflected by increased expression of glucose-regulated proteins GRP78 and GRP94,
      and by increased expression of transcription factors activating transcription
      factor 4 (ATF4) and C/EBP homologous protein (CHOP), and enhanced caspase 3
      activity. Additionally, ER stress also upregulated tumor necrosis factor-alpha
      (TNF-alpha). Simultaneous silencing of ATF4 and CHOP prevented upregulation of
      TNF-alpha. Knockdown of either ATF4 and CHOP or TNF-alpha by their siRNAs was
      able to reverse the ethanol-induced adipogenesis. CONCLUSION: Our data therefore
      revealed a role of ER stress and ATF4/CHOP in the ethanol-induced inhibition of
      osteogenesis, and activation of TNF-alpha signaling by ATF4/CHOP linking ER
      stress to adipogenic lineage in response to alcohol stimulation. This work should
      establish a new signaling pathway linking alcohol, ER stress, and TNF-alpha to
      loss of bone formation: Ethanol -> ER stress??? -> ATF4 & CHOP??? -> TNF-alpha???
      -> Osteoblasts???.

PMID- 24080828
TI  - Reciprocal interferences of TNF-alpha and Wnt1/beta-catenin signaling axes shift
      bone marrow-derived stem cells towards osteoblast lineage after ethanol exposure.
AB  - BACKGROUND/AIMS: We have reported in a separate study that alcohol exposure
      triggers activation of the TNF-alpha signaling pathway leading to an adverse
      shift of multipotential mesenchymal stem cells in bone marrow (BMSCs) away from
      osteogenesis towards adipogenesis. However, inhibition of TNF-alpha signaling
      only yielded moderate inhibition of adipogenesis. Here we showed that in addition
      to promoting the TNF-alpha signaling, alcohol also suppressed the Wnt1/beta
      catenin signaling pathway. METHODS: We treated primary BMSCs from human subjects
      with alcohol for 24 days. We measured changes of genes related to endoplasmic
      reticulum (ER) stress, adipogenic markers and osteogenic markers using
      quantitative real-time RT-PCR and Western blot analysis. We performed Alizarin
      red staining for osteogenesis. We also conducted assays for osteogenic biomarkers
      alkaline phosphatase, collagen-I and osteocalcin. RESULTS: Wnt/beta-catenin
      signaling was markedly activated in BMSCs treated with osteogenic inducers
      relative to the control cells, as indicated by the increased levels of nuclear
      beta-catenin along with reduced levels of cytosolic beta-catenin, as well as
      increased protein levels of Wnt1. Activation of Wnt/beta-catenin signaling was
      significantly suppressed in BMSCs exposed to alcohol, which was reflected by
      downregulated expression of osteogenic marker genes Osf2/Cbfa1, osteopontin and
      osteocalcin, upregulated adipogenic marker PPARgamma2 and aP2, and reduced number
      of calcifcation nodules. In contrast, activation of Wnt/beta-catenin signaling by
      BIO favored osteogenesis even in the presence of alcohol. Simultaneous activation
      of Wnt1 by BIO and inhibition of TNF-alpha by 3,6'-dithiothalidomide produced
      synergetic suppression of ethanol-induced adipogenic lineage compared to
      interference with either of them alone. CONCLUSION: This remarkable shift of
      BMSCs towards osteoblast lineage suggests the superiority of concordant and
      reciprocal interferences of the TNF-alpha and Wnt/beta-catenin pathways for
      promoting osteogenesis.

PMID- 24080829
TI  - Akt2 deficiency is associated with anxiety and depressive behavior in mice.
AB  - BACKGROUND: The economic burden associated with major depressive disorder and
      anxiety disorders render both disorders the most common and debilitating
      psychiatric illnesses. To date, the exact cellular and molecular mechanisms
      underlying the pathophysiology, successful treatment and prevention of these
      highly associated disorders have not been identified. Akt2 is a key protein in
      the phosphatidylinositide-3 (PI3K) / glycogen synthase 3 kinase (GSK3) signaling
      pathway, which in turn is involved in brain-derived neurotrophic factor (BDNF)
      effects on fear memory, mood stabilisation and action of several antidepressant
      drugs. The present study thus explored the impact of Akt2 on behaviour of mice.
      METHODS: Behavioural studies (Open-Field, Light-Dark box, O-Maze, Forced Swimming
      Test, Emergence Test, Object Exploration Test, Morris Water Maze, Radial Maze)
      have been performed with Akt2 knockout mice (akt(-/-)) and corresponding wild
      type mice (akt(+/+)). RESULTS: Anxiety and depressive behavior was significantly
      higher in akt(-/-) than in akt(+/+) mice. The akt(-/-) mice were cognitively
      unimpaired but displayed increased anxiety in several behavioral tests (O-Maze
      test, Light-Dark box, Open Field test). Moreover, akt(-/-) mice spent more time
      floating in the Forced Swimming test, which is a classical feature of
      experimental depression. CONCLUSION: Akt2 might be a key factor in the
      pathophysiology of depression and anxiety.

PMID- 24080830
TI  - DNA damage and cell cycle arrest induced by protoporphyrin IX in sarcoma 180
      cells.
AB  - BACKGROUND: Porphyrin derivatives have been widely used in photodynamic therapy
      as effective sensitizers. Protoporphyrin IX (PpIX), a well-known hematoporphyrin
      derivative component, shows great potential to enhance light induced tumor cell
      damage. However, PpIX alone could also exert anti-tumor effects. The mechanisms
      underlying those direct effects are incompletely understood. This study thus
      investigated the putative mechanisms underlying the anti-tumor effects of PpIX on
      sarcoma 180 (S180) cells. METHODS: S180 cells were treated with different
      concentrations of PpIX. Following the treatment, cell viability was evaluated by
      the 3-(4, 5- dimethylthiazol-2-yl)-2, 5-diphenyltetrazoliumbromide (MTT) assay;
      Disruption of mitochondrial membrane potential was measured by flow cytometry;
      The trans-location of apoptosis inducer factor (AIF) from mitochondria to nucleus
      was visualized by confocal laser scanning microscopy; DNA damage was detected by
      single cell gel electrophoresis; Cell cycle distribution was analyzed by DNA
      content with flow cytometry; Cell cycle associated proteins were detected by
      western blotting. RESULTS: PpIX (>= 1 ug/ml) significantly inhibited
      proliferation and reduced viability of S180 cells in a dose-dependent manner.
      PpIX rapidly and significantly triggered mitochondrial membrane depolarization,
      AIF (apoptosis inducer factor) translocation from mitochondria to nucleus and DNA
      damage, effects partially relieved by the specific inhibitor of MPTP
      (mitochondrial permeability transition pore). Furthermore, S phase arrest and
      upregulation of the related proteins of P53 and P21 were observed following 12
      and 24 h PpIX exposure. CONCLUSION: PpIX could inhibit tumor cell proliferation
      by induction of DNA damage and cell cycle arrest in the S phase.

PMID- 24080831
TI  - Intensive short-term dynamic psychotherapy associated with decreases in
      electroconvulsive therapy on adult acute care inpatient ward.

PMID- 24080832
TI  - Polyion complex libraries possessing naturally occurring differentiation for
      pattern-based protein discrimination.
AB  - Polyion complexes with naturally occurring differentiation of enzymes serve to
      create receptor libraries with high differentiability and lower synthetic demands
      for pattern-based protein discrimination. 

PMID- 24080833
TI  - Photoluminescence enhancement of carbon dots by gold nanoparticles conjugated via
      PAMAM dendrimers.
AB  - Carbon dots (CDs) have many fascinating fluorescent properties, however, their
      low quantum yield limits their applications. In this study, the photoluminescence
      (PL) of CDs in the vicinity of gold nanoparticles (Au NPs) is enhanced
      significantly due to the surface plasmon resonance (SPR) of the Au NPs. This is
      achieved by conjugating Au NPs and CDs to dendrimers (PAMAM) through an amidation
      reaction, resulting in the formation of the Au-PAMAM-CD conjugates. The maximum
      62-fold enhancement was obtained with an optimized molar ratio between Au NPs,
      PAMAM, and CDs. In this process, PAMAM, which serves as a spacer, can keep Au NPs
      and CDs at an appropriate distance for PL enhancement. The adjustment of the
      amount of Au NPs or CDs linked to PAMAM can induce the optimum PL enhancement.
      This strategy can be easily applied to different metal-space-fluorophore systems
      to enhance the fluorescence of fluorophores. 

PMID- 24080834
TI  - Alzheimer disease: Variations in mitochondrial DNA predict AD-related brain
      atrophy.

PMID- 24080835
TI  - Efficient delivery of siRNA by atelocollagen in a murine laser-induced choroidal
      neovascularization model.
AB  - PURPOSE: Previous studies have shown that small interfering RNAs (siRNAs) could
      suppress angiogenesis via stimulation of toll-like receptor-3 (TLR3). The purpose
      of this study was to determine the efficacy of atelocollagen to deliver siRNA
      without TLR3 stimulation in the laser-induced choroidal neovascularization (CNV)
      model. METHODS: CNV was induced by laser injury in C57BL/6J mice and volumes were
      measured 7 days later. Nontargeted siRNA, 21-nucleotide (nt) siRNA-Luc
      (Luciferase) and 21-nt siRNA-Vegfa were injected into the vitreous following
      injury. Atelocollagen was incubated with naked 21-nt siRNAs before injection. To
      block TLR3 endosomal activity, chloroquine was injected intravitreously after
      laser injury. RESULTS: The mean CNV volumes were significantly smaller in the
      naked siRNA-Luc, naked siRNA-Vegfa, or siRNA-Vegfa/atelocollagen complex compared
      with PBS, atelocollagen or siRNA-Luc/atelocollagen complex-injected mice (p <
      0.05). CONCLUSION: These findings demonstrate that atelocollagen may deliver
      siRNA without nonspecific TLR3 stimulation in the murine laser-CNV model.

PMID- 24080836
TI  - Chain dynamics of surfactants in mesoporous silica.
AB  - Mesostructured porous materials possess unique surface, structural, and bulk
      properties that lead to important practical applications. By retaining structure
      directing species in the product material, mesostructured organic-inorganic
      composites are obtained which are of broad interest for fundamental studies of
      confinement effects and surface interaction on structural and dynamic properties
      of organic molecules. In the present study, solid state dipolar (13)C-(1)H NMR
      spectroscopy is applied to quantitatively characterize the conformational
      dynamics of organic surfactants in the mesostructured composite CTAB-MCM41. Such
      an approach does not require assumptions and adjustable parameters and reflects
      the changes in conformational dynamics without relying on specific motional
      models. The conformational dynamics of the surfactant confined in solid hexagonal
      arrays is compared to that in hexagonal aggregates formed in a concentrated
      aqueous solution. The study showed that in cylindrical pores of hexagonal
      mesoporous silica the order parameter gradually decreases towards the end of the
      chain. The degree of order and the order parameter profile is similar to that
      observed in hexagonal liquid crystalline phases. However, the mobility of
      segments close to the head group is more restricted compared to that in the
      mesophase, as the result of interaction with the solid silica interface. 

PMID- 24080837
TI  - DC magnetic susceptibility and neutron powder diffraction analysis of the
      perovskite-type compounds LaYbO3 and LaHoO3.
AB  - Magnetization measurements and neutron powder diffraction analyses followed by
      Rietveld refinement have been carried out in order to investigate the magnetic
      structures of LaYbO3 and LaHoO3. Both compounds exhibit a negative thermal
      expansion along the a and b axes. In LaYbO3 Yb(3+) spins order at 2.4 K according
      to a FyGz-type structure, belonging to the Pn'ma' magnetic space group.
      Conversely, LaHoO3 is paramagnetic down to 1.5 K.

PMID- 24080838
TI  - Assessment of problematic internet use by the Compulsive Internet Use Scale and
      the Internet Addiction Test: a sample of problematic and pathological gamblers.
AB  - This study aims to analyze psychometric properties and validity of the Compulsive
      Internet Use Scale (CIUS) and the Internet Addiction Test (IAT) and, second, to
      determine a threshold for the CIUS which matches the IAT cut-off for detecting
      problematic Internet use. A total of 292 subjects with problematic or
      pathological gambling (237 men, 55 women) aged 14-63 years and with private
      Internet use for at least 1 h per working or weekend day were recruited via
      different recruitment channels. Results include that both scales were internally
      consistent (Cronbach's alpha=0.9) and had satisfactory convergent validity
      (r=0.75; 95% CI 0.70-0.80). The correlation with duration of private Internet use
      per week was significantly higher for the CIUS (r=0.54) compared to the IAT
      (r=0.40). Among all participants, 25.3% were classified as problematic Internet
      users based on the IAT with a cut-off>=40. The highest proportion of congruent
      classified cases results from a CIUS cut-off >=18 (sensitivity 79.7%, specificity
      79.4%). However, a higher cut-off (>=21) seems to be more appropriate for
      prevalence estimation of problematic Internet use.

PMID- 24080839
TI  - Folic acid for the prevention of neural tube defects.

PMID- 24080840
TI  - Predictive factors for voiding dysfunction after transobturator slings.
AB  - PURPOSE: To identify the predictive factors for voiding dysfunction after
      transobturator slings. METHODS: We retrospectively reviewed the records of all
      patients who underwent a transobturator sling between March 2003 and December
      2008. A total of 514 women had available data with at least a six-week follow-up.
      Patients' demographics, preoperative symptoms, urodynamic testing including
      multichannel voiding studies and surgical variables were tabulated. Voiding
      dysfunction was defined by a catheterized or ultrasonographic postvoid residual
      greater than 100 cc (>=six weeks after the procedure) associated with any
      complaints of abnormal voiding. Univariate logistic regression analysis was
      performed with respect to postoperative voiding dysfunction. RESULTS: The patient
      population had a mean age of 58.5 +/- 12.9 years. Thirty-three out of 514
      patients (6.4%) had postoperative voiding dysfunction according to our
      definition, and 4 (0.78%) required sling transection. No differences were
      observed between normal and dysfunctional voiders in age, associated prolapse
      surgery, preoperative postvoid residual, preoperative urinary flow rate, prior
      pelvic surgery, and menopausal status. Valsalva efforts during the preoperative
      pressure flow study was the only predictive factor for postoperative voiding
      dysfunction, 72.4% dysfunctional versus 27.6% normal (p<0.001). CONCLUSION:
      Preoperative Valsalva maneuver during the micturition could identify those at
      risk for voiding dysfunction after transobturator sling, and it should be noted
      during preoperative counseling.

PMID- 24080841
TI  - Self-perception of sexual life and associated factors: a population study
      conducted in women aged 50 or more years.
AB  - PURPOSE: To evaluate the prevalence of women aged 50 years or more who are
      sexually active and their self-perception with respect to their sexual lives.
      Associated factors were also assessed. METHODS: A cross-sectional, population
      based, self-reported household survey involving 622 Brazilian women aged 50 years
      or more. Sociodemographic, clinical, and behavioral factors were evaluated. The
      sexual life self-perception was classified as very good, good, fair, poor, or
      very poor. Data were analyzed using the chi2 test, Fisher's exact test, and
      Poisson multiple regression analysis. Prevalence ratios and their 95% confidence
      intervals were also calculated. RESULTS: Of the women in this sample, 228 (36.7%)
      reported having a sexual life and, of these, 53.5% classified it as very good or
      good, while 46.5% considered it fair, poor, or very poor. The bivariate analysis
      indicated that being postmenopausal (p=0.025) and using natural remedies to treat
      the menopause (p=0.035) were factors associated with the woman classifying their
      sexual lives as fair, poor, or very poor. Multiple regression analysis showed
      that more women who had used or were currently using natural remedies for the
      menopause scored their sexual lives as fair, poor, or very poor. CONCLUSIONS:
      More than half the women aged 50 years or more in this study were not sexually
      active. A poorer sexual life self-perception was associated with the use of
      natural remedies to treat menopausal symptoms. This may indicate a need to
      improve the way in which these women are evaluated and treated. Women's
      assessment of their own sexual lives may prove a useful tool in clinical
      practice.

PMID- 24080842
TI  - [Evaluation of sexual function in postmenopause women with metabolic syndrome].
AB  - PURPOSE: To evaluate sexual function in postmenopausal women diagnosed with
      metabolic syndrome. METHODS: Case-control study with 195 postmenopausal women
      (amenorrhea >=1 year, FSH>=30 mIU/mL, aged 43 to 69 years) seen at the Department
      of Obstetrics and Gynecology, School of Medical Sciences of Santa Casa de Sao
      Paulo and in the Basic Units of the Family Health Program of Sao Paulo. Clinical
      data were collected, and body mass index and waist circumference were evaluated.
      Total cholesterol, HDL and LDL cholesterols, triglycerides, and fasting glucose
      were determined for biochemical analysis. We considered women to have the
      metabolic syndrome when they met three or more diagnostic criteria: waist
      circumference>88 cm and triglycerides >=150 mg/dL; cholesterol HDL <50 mg/dL;
      blood pressure >=130/85 mmHg, and fasting glucose >=110 mg/dL. The participants
      were divided into Control Group (n=87) and Metabolic Syndrome Group (n=108). The
      Female Sexual Function Index (FSFI) was employed to assess the sexual function.
      RESULTS: Mean age was 54.0 +/- 4.7 years. The rate of sexual dysfunction was
      significantly higher in women with the metabolic syndrome than in the Control
      Group, both when considering FSFI <26.5 (90/108 [83.3%] versus 42/87 [48.2%],
      p<0.0001) and FSFI <23 (62/108 [57.4%] versus 16/87 [18.39%], p<0.001). The
      domains desire, arousal, lubrication, orgasm (p<0.001), and satisfaction
      (p=0.002) had lower scores in women with the metabolic syndrome. For the pain
      scores, there was no significant difference (p=0.57) between groups. All
      components of the metabolic syndrome diagnosis were associated with higher levels
      of sexual dysfunction (p<0.001). CONCLUSION: Postmenopausal women with metabolic
      syndrome present more frequently sexual dysfunction than those of the same age
      who do not have it.

PMID- 24080843
TI  - [Factors associated with fetal brain-sparing effect in patients with hypertension
      in pregnancy].
AB  - PURPOSE: To determine perinatal outcomes and factors associated with fetal brain
      sparing effect diagnosed by Doppler flow velocimetry in patients with arterial
      hypertension. METHODS: We performed a cross-sectional retrospective study
      including 129 pregnant women with arterial hypertension and submitted to Doppler
      flow velocimetry, within fifteen days before delivery. Women with multiple
      pregnancies, fetal malformations, genital bleeding, placenta praevia, premature
      rupture of membranes, smoking, illicit drug use and chronic diseases were
      excluded. We analyzed the biological, socio-demographic and obstetric
      characteristics, as well the perinatal outcomes. To determine the association
      between variables, we used the chi2 test, Fisher's exact test and Student's t
      test. Multiple logistic regression analysis was performed to determine the
      factors associated with fetal centralization. RESULTS: Pre-eclampsia was the most
      frequent hypertensive disorder (53.5%) and fetal brain sparing effect was
      observed in 24.0% of fetuses. The prenatal factors associated with fetal brain
      sparing were the persistence of bilateral protodiastolic notches in uterine
      arteries (OR 3.6; 95%CI 1.4 - 9.4; p=0.009) and intrauterine growth restriction
      (IUGR) (OR 3.3; 95%CI 1.2 - 9.3; p=0.02). The perinatal outcomes associated with
      fetal brain sparing were gestational age <32 weeks, small for gestational age
      (SGA) infants, birth weight <2,500 g and perinatal death. There was no
      association with other maternal or neonatal variables. CONCLUSIONS: The main
      factors associated with fetal brain sparing were persistence of uterine arteries
      notches, IUGR, and increased frequency of adverse perinatal outcomes.

PMID- 24080844
TI  - Correlation between placental thickness in the second and third trimester and
      fetal weight.
AB  - PURPOSE: To investigate relationship between placental thickness during the
      second and third trimesters and placental and birth weights. METHODS: From
      January 2011 to June 2012, a total of 250 singleton pregnant women presented at
      our antenatal clinic were enrolled in this prospective study. All recruited women
      were assessed at the 1st trimester screening for baseline demographic and
      obstetric data. The placental thickness was measured trans-abdominally by placing
      the ultrasound transducer perpendicularly to the plane of the placenta, in the
      area of the cord insertion at second and third trimester. Pearson's correlation
      analysis was used to establish the degree of relationship between placental
      thickness and birth and placental weights. RESULTS: Of 250 recruited
      participants, 205 women were able to complete the study. The mean age of cases
      was 26.4 +/- 5.1. Values of mean birth and placental weights were 305.56 +/-
      657.0 and 551.7 +/- 104.8 grams respectively. Ultrasonographic measures of
      placental thickness in second and third trimester and changes between them were
      21.68 +/- 4.52, 36.26 +/- 6.46 and 14.67 +/- 5.67 mm respectively. There was a
      significant positive correlation between placental thickness and birth weight in
      the second and third trimesters (r=0.15, p=0.03; r=0.14, p=0.04 correspondingly).
      CONCLUSION: According to our study, birth weight has a positive relation with
      both second and third trimester placental thickness; however, placental thickness
      change could not predict low birth weight.

PMID- 24080845
TI  - [Non adherence to cancer screening guidelines for cervical cancer among women who
      attended prenatal care].
AB  - PURPOSE: To estimate the prevalence and identify the factors associated with
      delayed pap smear test of the cervix (carried out more than three years ago)
      among mothers with sons under two years of age, who attended the prenatal care.
      METHODS: Cross-sectional, population-based household survey. Women with sons
      under two years old, living in the northern area of the city of Juiz de Fora
      (MG), Brazil, were interviewed. Stratification and clustering were used in a
      complex sampling procedure. We applied a survey questionnaire to capture women's
      demographic and socioeconomic characteristics of women and information about
      prenatal and practices for preventing cancer of the cervix. For statistical
      analysis of the possible bivariate association of factors, we used chi2 test and
      a logistic regression model with the explanatory variables that had a
      significance less than or equal to 0.05 in the bivariate analysis. RESULTS: We
      found a delayed test prevalence of 26.6% (95%CI 21.3 - 32.6), including women who
      were never submitted to the exam. The variables associated with the non-adherence
      to the examination within the stipulated time were: to be married (OR 0.5; 95%CI
      0.2 - 0.9), and divorced/widowed (OR 0.1; 95%CI 0.02 - 0,8), having performed
      gynecological examination in prenatal care (OR 0.3; 95%CI 0.1 - 0.6) and number
      of prenatal visits (OR 0.09; 95%CI 0.03 - 0.25 for more than 11 visits), being
      all protection factors. CONCLUSIONS: The prevalence of adherence to Pap smear
      guidelines is slightly lower than the percentage recommended by the World Health
      Organization. Apart from that, the fact that the woman was submitted to the
      prenatal care did not guarantee the adherence to Pap smear frequency guidelines.

PMID- 24080846
TI  - [Sclerosing stromal tumor of the ovary associated with a Meigs' syndrome and
      pregnancy: a case report].
AB  - The sclerosing stromal tumor of the ovary is an extremely rare benign tumor more
      common in young women and without specific symptoms in most cases. Less than 150
      cases have been described, of which 8 were diagnosed during pregnancy. In this
      report, we describe the association between sclerosing stromal tumor of the
      ovary, Meigs' syndrome and elevated levels of CA-125 in term pregnancy. 

PMID- 24080847
TI  - Validation of the Quality of Life Questionnaire of the European Foundation for
      Osteoporosis-31 in Spanish postmenopausal women.
AB  - OBJECTIVE: The Quality of Life Questionnaire of the European Foundation for
      Osteoporosis-31 (QUALEFFO-31) is a reliable and validated questionnaire that
      assesses quality of life in osteoporotic women. Our objective was to analyze the
      reliability and validity of the Spanish version of QUALEFFO-31 and its ability to
      discriminate between women with osteoporosis and women without osteoporosis in a
      Spanish postmenopausal population. METHODS: One hundred eighteen women (aged 50
      65 y) completed the Spanish version of QUALEFFO-31. Bone mineral density was
      measured by dual-energy x-ray densitometry. Internal consistency and test-retest
      reliability were analyzed. Concurrent validity of QUALEFFO-31 was evaluated using
      Spearman's rank correlation coefficient with the 36-item Short-Form Health Survey
      (SF-36). To determined responsiveness, we analyzed mean differences between
      osteoporotic and nonosteoporotic women and performed receiver operating
      characteristic curve analysis. RESULTS: The Spanish version of QUALEFFO-31 has
      shown excellent test-retest reliability with a high intraclass correlation
      coefficient for all its domains, especially for the total score (0.988; P <
      0.001), and good internal consistency with optimal Cronbach alpha values in all
      scales (0.70-0.90). In concurrent validity analysis, QUALEFFO-31 total score
      showed a high and negative correlation with several scales of the SF-36 (P <
      0.001). In responsiveness analysis, significant differences in the pain (P =
      0.002) and QUALEFFO-31 total score (P = 0.004) scales were found between
      osteoporotic and nonosteoporotic women. No differences in areas under the
      receiver operating characteristic curve were found between the QUALEFFO-31 and
      the SF-36 scales. CONCLUSIONS: The Spanish version of QUALEFFO-31 has good
      internal consistency, concurrent validity, and test-retest reliability, with
      satisfactory general psychometric properties, and is a valid tool for
      discriminating between osteoporotic and nonosteoporotic postmenopausal women aged
      50 to 65 years.

PMID- 24080848
TI  - Aromatase inhibitors affect vaginal proliferation and steroid hormone receptors.
AB  - OBJECTIVE: Women with breast cancer who are treated with aromatase inhibitors
      often experience vaginal atrophy symptoms and sexual dysfunction. This work aims
      to study proliferation and the presence and distribution of steroid hormone
      receptors in vaginal biopsies in relation to vaginal atrophy and vaginal pH in
      women with breast cancer who are on adjuvant endocrine treatment and in healthy
      postmenopausal women. METHODS: This is a cross-sectional study that compares
      postmenopausal aromatase inhibitor-treated women with breast cancer (n = 15) with
      tamoxifen-treated women with breast cancer (n = 16) and age-matched
      postmenopausal women without treatment (n = 19) or with vaginal estrogen therapy
      (n = 16). Immunohistochemistry was used to study proliferation and steroid
      hormone receptor staining intensity. Data was correlated with estrogen and
      androgen levels, vaginal atrophy scores, and vaginal pH. RESULTS: Aromatase
      inhibitor-treated women had a lower grade of proliferation, weaker progesterone
      receptor staining, and stronger androgen receptor staining, which correlated with
      plasma estrone levels, vaginal atrophy scores, and vaginal pH. CONCLUSIONS: Women
      with aromatase inhibitor-treated breast cancer exhibit reduced proliferation and
      altered steroid hormone receptor staining intensity in the vagina, which are
      related to clinical signs of vaginal atrophy. Although these effects are most
      probably attributable to estrogen suppression, a possible local inhibition of
      aromatase cannot be ruled out.

PMID- 24080850
TI  - Serum levels of polyunsaturated fatty acids and the risk of posttraumatic stress
      disorder.

PMID- 24080849
TI  - Association between the vaginal microbiota, menopause status, and signs of
      vulvovaginal atrophy.
AB  - OBJECTIVE: The vaginal microbiota helps protect the female genital tract from
      disease. We sought to describe the composition of the vaginal microbiota in
      premenopausal, perimenopausal, and postmenopausal women and to explore the
      association between the microbiota and vulvovaginal atrophy (VVA). METHODS:
      Eighty-seven women (aged 35-60 y) were classified as premenopausal (n = 30),
      perimenopausal (n = 29), or postmenopausal (n = 28) according to Stages of
      Reproductive Aging Workshop guidelines. Midvaginal bacterial community
      composition was characterized by 16S ribosomal RNA gene analysis. RESULTS:
      Bacterial communities clustered into six community state types (CSTs), of which
      four were dominated by Lactobacillus crispatus, Lactobacillus gasseri,
      Lactobacillus iners, or Lactobacillus jensenii, and two (CST IV-A and CST IV-B)
      had low relative abundance of Lactobacillus. CST IV-A was characterized by
      Streptococcus and Prevotella, whereas CST IV-B was characterized by Atopobium.
      There were significant associations between menopause stage and CST (P = 0.004)
      and between VVA and CST (P = 0.002). Perimenopausal women were more likely to be
      classified as CST IV-A or L. gasseri CST, whereas postmenopausal women were often
      classified as CST IV-A. CSTs dominated by L. crispatus and L. iners were more
      prevalent in premenopausal women. Nineteen participants had signs of mild or
      moderate VVA. Compared with women with no VVA, the vaginal microbiota of women
      with mild or moderate atrophy had 25-fold greater odds of being classified as CST
      IV-A versus L. crispatus CST (adjusted odds ratio, 25.89; 95% credible interval,
      2.98-406.79). CONCLUSIONS: A distinct bacterial community state (CST IV-A) with a
      low relative abundance of Lactobacillus is associated with VVA. Future studies
      recruiting a larger number of women are needed to replicate the findings. This
      study provides an impetus for future longitudinal studies designed to manage,
      modulate, and restore vaginal microbiota homeostasis, which would provide
      stronger evidence for a causal relationship with VVA and ultimately improve the
      treatment and prevention of atrophic vaginitis in menopause.

PMID- 24080851
TI  - A 3-year follow-up of sun behavior in patients with cutaneous malignant melanoma.
AB  - IMPORTANCE UV radiation (UVR) exposure is the primary environmental risk factor
      for developing cutaneous malignant melanoma (CMM). OBJECTIVE To measure changes
      in sun behavior from the first until the third summer after the diagnosis of CMM
      using matched controls as a reference. DESIGN, SETTING, AND PARTICIPANTS Three
      year follow-up, observational, case-control study performed from May 7 to
      September 22, 2009, April 17 to September 15, 2010, and May 6 to July 31, 2011,
      at a university hospital in Denmark of 21 patients with CMM and 21 controls
      matched to patients by sex, age, occupation, and constitutive skin type
      participated in the study. Exposure to UVR was assessed the first and second
      summers (n=20) and the first and third summers (n=22) after diagnosis. Data from
      40 participants were analyzed. MAIN OUTCOMES AND MEASURES Exposure to UVR was
      assessed by personal electronic UVR dosimeters that measured time-related UVR in
      standard erythema dose (SED) and corresponding sun diaries (mean, 74 days per
      participant each participation year). RESULTS Patients' daily UVR dose and UVR
      dose in connection with various behaviors increased during follow-up (quantified
      as an increase in daily UVR dose each year; all days: mean, 0.3 SED; 95% CI, 0.05
      0.5 SED; days with body exposure: mean, 0.6 SED; 95% CI, 0.07-1.2 SED; holidays:
      mean, 1.2 SED; 95% CI, 0.3-2.1 SED; days abroad: 1.9 SED; 95% CI, 0.4-3.4 SED;
      and holidays with body exposure: mean, 2.3 SED; 95% CI, 1.1-3.4 SED). After the
      second year of follow-up, patients' UVR dose was higher than that of controls,
      who maintained a stable UVR dose. No difference was found between groups in the
      number of days with body exposure or the number of days using sunscreen in the
      second and third years of follow-up. CONCLUSIONS AND RELEVANCE Our findings
      suggest that patients with CMM do not maintain a cautious sun behavior in
      connection with an increase in UVR exposure, especially on days with body
      exposure, when abroad, and on holidays.

PMID- 24080852
TI  - Hippocampus-related cognitive impairments in young apoE4 targeted replacement
      mice.
AB  - We presently investigated the effects of apolipoprotein E4 (apoE4), the most
      prevalent genetic risk factor for Alzheimer's disease, on the cognitive
      performance of young targeted replacement apoE4 mice. We revealed that these mice
      were impaired in the object recognition and Morris water maze tests, both of
      which are associated with hippocampal learning and memory, relative to that of
      the apoE3 mice. These results are consistent with previous histological and
      biochemical findings that hippocampal neurons are specifically affected by apoE4.
      The suggestion that the behavioral impairments of the apoE4 mice are related to
      the hippocampal neuropathology of these mice is further supported by the fear
      conditioning test. This test revealed that the performance of the apoE4 mice in
      the contextual component, which is hippocampus related, was impaired, whereas
      their cued test response, which is amygdala driven, was not. The stress levels of
      the apoE4 and apoE3 mice, as unraveled by the light/dark anxiety test, were
      similar, suggesting that the observed cognitive impairments of the apoE4 mice are
      not related to differences in the basal anxiety levels of these mice. In
      conclusion, the present study shows that young apoE4 targeted replacement mice
      are impaired in numerous hippocampus-related learning and memory tasks.

PMID- 24080853
TI  - Effects of puerarin on cardiac differentiation and ventricular specialization of
      murine embryonic stem cells.
AB  - AIMS: It is important to screen and identify chemical compounds to improve the
      efficiency of cardiac differentiation and specialization of embryonic stem (ES)
      cells. The objective of this study was to investigate the effect of puerarin, a
      natural phytoestrogen, on the in vitro cardiac differentiation and ventricular
      specialization of murine ES cells. METHODS: Cardiac differentiation of murine ES
      cells was performed by embryoid body (EB)-based differentiation method.
      Quantitative RT-PCR, flow cytometry and immunofluorescence were employed to
      identify cardiomyocytes (CMs) derived from murine ES cells (mES-CMs). Patch clamp
      was used to study the electrophysiological properties of CMs. RESULTS: We found
      that continuous puerarin treatment significantly increased the population of ES
      CMs which express typical cardiac markers and are electrophysiological intact.
      Puerarin treatment shifted the cardiac phenotype from pacemaker-like cells to
      ventricular-like cells, which were Mlc2v-positive and present typical ventricular
      like AP. Puerarin up-regulated transcripts involved in cardiac differentiation
      and ventricular specialization of ES cells. CONCLUSION: Our results suggest that
      puerarin promotes cardiac differentiation, and significantly enhances the
      specialization of mES cells into ventricular-like CMs. Puerarin may be used to
      increase the yield of ventricular mES-CMs during in vitro differentiation.

PMID- 24080856
TI  - A FRET-based ratiometric fluorescent and colorimetric probe for the facile
      detection of organophosphonate nerve agent mimic DCP.
AB  - A FRET ratiometric fluorescent probe enabling a fast and highly sensitive
      response to OP nerve agent mimic DCP within 1 min and with as low as 0.17 ppm
      concentration detection limit has been developed. Moreover, the probe exhibits
      noticeable color changes under UV light and even with the naked eye. It is also
      demonstrated that it can detect both liquid and gas nerve agents. 

PMID- 24080855
TI  - The EFEMP1 gene: a frequent target for epigenetic silencing in multiple human
      pituitary adenoma subtypes.
AB  - BACKGROUND/AIMS: In a genome-wide investigation we recently identified the EGF
      containing fibulin-like extracellular matrix protein 1 gene, EFEMP1, as
      hypermethylated in growth hormone-secreting adenoma. METHODS: In an independent
      cohort we determined expression of EFEMP1, CpG island methylation and histone
      tail modification status. The causal consequences of epigenetic modification were
      determined through epidrug-induced reversal and enforced EFEMP1 expression in GH3
      cells. RESULTS: The majority of adenomas, irrespective of subtype, show reduced
      EFEMP1 expression. However, epigenetic change, as determined by CpG island
      methylation, was not invariantly associated with decreased EFEMP1 expression.
      Conversely, chromatin immunoprecipitation assays revealed enrichment for
      modifications associated with either active or silenced genes in adenoma that did
      or did not express EFEMP1 respectively. In AtT-20 and GH3 cells a causal
      relationship between epigenetic silencing and expression of EFEMP1 was
      established where co-incubation with the epidrugs zebularine and TSA induced
      expression of EFEMP1 and concomitant histone tail modifications toward those
      associated with expressed genes. Enforced expression of EFEMP1 in GH3 cells was
      without effect on cell proliferation or apoptotic end-points, however inhibition
      of endogenous matrix metalloproteinase (MMP)-2 expression was apparent. Primary
      adenomas did not show this relationship, however a positive correlation was
      apparent with the MMP7 transcript and perhaps reflects cell or species
      differences. CONCLUSIONS: The protein product of the EFEMP1 gene, fibulin-3, is
      reported to impact on multiple pathways in a cell-specific context. Subtype
      independent loss of EFEMP1 expression in the majority of primary adenomas should
      prompt more detailed investigation in this tumour type.

PMID- 24080858
TI  - Nerve fiber layer thickness in eyes treated with red versus green laser in
      proliferative diabetic retinopathy: short-term results.
AB  - PURPOSE: To evaluate changes of retinal nerve fiber layer (RNFL) thickness after
      panretinal photocoagulation (PRP) in red versus green laser-treated eyes.
      PROCEDURE: This is a prospective, randomized, fellow-eye controlled clinical
      trial conducted on 60 eyes of 30 patients (mean age 52.3 +/- 7.8 years; 57% male)
      with early- to high-risk proliferative diabetic retinopathy type II diabetes who
      received standard red or green laser treatment. Scanning laser polarimetry (GDx)
      was performed to evaluate RNFL thickness at baseline and at week 6. RESULTS: Only
      22 patients (44 eyes) could perform reliable GDx tests. At week 6 after PRP, the
      RNFL thickness increased by an average of 3.35 +/- 9.18 um (p = 0.02) and 2.08 +/
      4.75 um (p = 0.04) in the red and green laser groups, respectively. There was no
      significant correlation between changes in RNFL thickness and the number of laser
      burns, age, HbA1c or blood pressure. The difference in the change of the RNFL
      thickness between the red and green laser groups was not significant (p = 0.8).
      CONCLUSION: Though RNFL thickness was increased significantly 6 weeks after PRP
      with red and green laser in comparison to baseline, there was no significant
      difference in RNFL thickness between red and green laser groups.

PMID- 24080854
TI  - Toll-like receptor 9 is required for chronic stress-induced immune suppression.
AB  - OBJECTIVES: Mental and physical stress can suppress the immune system in both
      humans and animals. The mechanism by which stress affects immune responses,
      however, remains poorly defined. Toll-like receptors (TLRs) play a key role in
      modulating immune responses and cell survival. The mechanisms by which TLRs
      modulate chronic stress are largely unexplored. METHODS: Six- to 8-week-old male
      mice were subjected to chronic 12-hour daily physical restraint stress. Apoptotic
      cells were determined by the terminal deoxynucleotidyl transferase-mediated
      deoxyuridine triphosphate nick end labeling (TUNEL) assay. We examined cytokine
      levels by enzyme-linked immunosorbent Assay (ELISA). The expression of CYP11A1
      was determined by quantitative real-time RT-PCR. RESULTS: TLR9-deficient mice
      were resistant to chronic stress-induced lymphocyte apoptosis. In addition, in
      TLR9 knockout (KO) mice, chronic stress-induced upregulation of corticosterone
      levels was significantly decreased. Notably, lymphocytes from both TLR9 KO and
      wild-type mice were similarly sensitive to corticosteroid-induced cell apoptosis.
      Moreover, TLR9 deficiency blocked the chronic stress-induced imbalance in T
      helper (Th) 1 and Th2 cytokine levels. CONCLUSION: Taken together, our findings
      reveal that TLR9 plays an essential role in chronic stress-induced immune
      suppression.

PMID- 24080859
TI  - OH-initiated oxidation of sub-micron unsaturated fatty acid particles.
AB  - The heterogeneous reaction of OH radicals with sub-micron unsaturated fatty acid
      particles in the presence of H2O2 and O2 is studied to explore how surface OH
      addition reactions initiate chain reactions that rapidly transform the chemical
      composition of an organic particle. In the presence of 20.7 ppm [H2O2] in a 10%
      mixture of O2 in N2, the effective uptake coefficients of oleic acid, linoleic
      acid and linolenic acid are found to be 1.72 +/- 0.08, 3.75 +/- 0.18 and 5.73 +/-
      0.14, respectively. These effective uptake coefficients are larger than unity,
      providing clear evidence for particle-phase secondary chain chemistry. The
      effective uptake coefficient increases linearly with the number of C=C double
      bonds in the unsaturated fatty acid molecule. Elemental composition analysis
      reveals that there is an addition of, on average, 0.57 +/- 0.02, 0.61 +/- 0.01
      and 0.73 +/- 0.04 O atoms per reactive loss of oleic acid, linoleic acid and
      linolenic acid, respectively, which suggests that OH addition to the C=C double
      bond is not the sole reaction pathway that consumes the molecular species. These
      results suggest the potential presence of secondary reactions that consume the
      unsaturated fatty acid molecular species without increasing the particulate
      oxygen content. As the unsaturated fatty acid particles become more oxygenated,
      volatilization also becomes significant. The magnitudes of the effective uptake
      coefficients are found to be dependent on the concentrations of OH, O2 and H2O2
      in the flow reactor. A plausible reaction mechanism is presented to show how
      surface OH addition reactions initiate chain reactions that rapidly transform an
      unsaturated organic particle's physicochemical properties.

PMID- 24080860
TI  - Rheumatoid arthritis: Autophagy: a dual role in the life and death of RASFs.

PMID- 24080862
TI  - Spondyloarthritis: From undifferentiated SpA to ankylosing spondylitis.

PMID- 24080863
TI  - Inflammatory myopathies: T(REG)-cell deficiency and abnormal muscle antigen
      exposure important to the development of myositis.

PMID- 24080861
TI  - Platelet-rich plasma for managing pain and inflammation in osteoarthritis.
AB  - Osteoarthritis (OA) is a common disease involving joint damage, an inadequate
      healing response and progressive deterioration of the joint architecture.
      Autologous blood-derived products, such as platelet-rich plasma (PRP), are key
      sources of molecules involved in tissue repair and regeneration. These products
      can deliver a collection of bioactive molecules that have important roles in
      fundamental processes, including inflammation, angiogenesis, cell migration and
      metabolism in pathological conditions, such as OA. PRP has anti-inflammatory
      properties through its effects on the canonical nuclear factor kappaB signalling
      pathway in multiple cell types including synoviocytes, macrophages and
      chondrocytes. PRP contains hundreds of different molecules; cells within the
      joint add to this milieu by secreting additional biologically active molecules in
      response to PRP. The net results of PRP therapy are varied and can include
      angiogenesis, the production of local conditions that favour anabolism in the
      articular cartilage, or the recruitment of repair cells. However, the molecules
      found in PRP that contribute to angiogenesis and the protection of joint
      integrity need further clarification. Understanding PRP in molecular terms could
      help us to exploit its therapeutic potential, and aid the development of novel
      treatments and tissue-engineering approaches, for the different stages of joint
      degeneration. 

PMID- 24080864
TI  - Intake of radioactive materials as assessed by the duplicate diet method in
      Fukushima.
AB  - A large quantity of radioactive materials was released from Reactor-II of the
      Fukushima Daiichi Nuclear Power Plant (F-1 NPP). People living in the area
      affected by the release are concerned about internal exposures from the daily
      intakes of contaminated foodstuffs. In order to assess whether the people should
      be concerned, Co-op Fukushima (Consumer Co-operative in Fukushima Prefecture)
      conducted a broad survey of radiocaesium in daily meals for which local
      inhabitants voluntarily provided a set of duplicate meals. Analyses by the
      duplicate diet method were conducted from November 2011 to March 2012 and from
      June 2012 to September 2012, each covering 100 families throughout the
      prefecture. Among the 200 meals thus analysed, 12 were found to have (134)Cs
      and/or (137)Cs concentrations exceeding 1 Bq kg(-1). Even with the largest
      radiocaesium value in our survey, daily consumption of such meals throughout a
      year gave an annual committed effective dose that did not exceed 0.1 mSv.

PMID- 24080865
TI  - Tramadol abuse in a binge pattern in a young depressed woman.
AB  - BACKGROUND: Tramadol is a central analgesic with a unique pharmacological profile
      in that it is an opioid agonist and an inhibitor of serotonin and norepinephrine
      reuptake. We describe a case of abuse of tramadol in a binge pattern in a young
      woman who had initially received the prescription of tramadol as an analgesic as
      needed. CASE DESCRIPTION: The patient had no history of drug or alcohol abuse,
      but suffered from depression. Over time, she had increased the doses up to 30 ml
      of tramadol 100 mg/ml oral solution a week. She took the drug in consecutive
      'pinches', from afternoon to evening. Tramadol improved her mood, gave her
      euphoria, but also caused constipation and urinary retention. Detoxification was
      carried out by partial replacement with tramadol 100 mg extended release and
      gradual reduction of the number of pinches. The patient found it hard to follow
      the program because of withdrawal symptoms of an opioid type and especially
      because of the worsening of depression. CONCLUSION: The action of tramadol on the
      monoaminergic system is believed to be a factor that limits abuse liability and
      gives advantageous antidepressant-like properties, but it also involves the risk
      of inducing abuse of the analgesic to improve mood as if it were a stimulant.

PMID- 24080867
TI  - Criterion validity of the diagnostic criteria for psychosomatic research in
      patients with morbid obesity.

PMID- 24080868
TI  - Switching mechanism and reverse engineering of low-power Cu-based resistive
      switching devices.
AB  - In the recent past, filamentary-based resistive switching devices have emerged as
      predominant candidates for future non-volatile memory storage. Most of the
      striking characteristics of these devices are still limited by the high power
      consumption and poor understanding of the intimate resistive switching mechanism.
      In this study, we present an atomic scale study of the filament formation in CuTe
      Al2O3 by using a conductive scanning probe tip to analyse the shape and
      dimensions of the filament. Filaments studied were either created within a normal
      device or locally formed while using the tip as the top electrode. We demonstrate
      that it is possible to create with C-AFM a filament with a signature identical to
      a device (i.e. two orders of magnitude resistance window, 10(4) s retention
      operating at 5 MUA). This is obtained by a dedicated material and resistance
      selection for the conductive tip. The filamentary mechanism of fully processed
      devices is demonstrated and observed by C-AFM. Filaments created with C-AFM can
      be repeatedly cycled and the ON state presents a 20 nm highly conductive spot
      which can be repeatedly turned into a poorly conductive path in the OFF state. 

PMID- 24080866
TI  - Adverse events associated with mohs micrographic surgery: multicenter prospective
      cohort study of 20,821 cases at 23 centers.
AB  - IMPORTANCE: Detailed information regarding perioperative risk and adverse events
      associated with Mohs micrographic surgery (MMS) can guide clinical management.
      Much of the data regarding complications of MMS are anecdotal or report findings
      from single centers or single events. OBJECTIVES: To quantify adverse events
      associated with MMS and detect differences relevant to safety. DESIGN, SETTING,
      AND PARTICIPANTS: Multicenter prospective inception cohort study of 21 private
      and 2 institutional US ambulatory referral centers for MMS. Participants were a
      consecutive sample of patients presenting with MMS for 35 weeks at each center,
      with staggered start times. EXPOSURE: Mohs micrographic surgery. MAIN OUTCOMES
      AND MEASURES Intraoperative and postoperative minor and serious adverse events.
      RESULTS: Among 20 821 MMS procedures, 149 adverse events (0.72%), including 4
      serious events (0.02%), and no deaths were reported. Common adverse events
      reported were infections (61.1%), dehiscence and partial or full necrosis
      (20.1%), and bleeding and hematoma (15.4%). Most bleeding and wound-healing
      complications occurred in patients receiving anticoagulation therapy. Use of some
      antiseptics and antibiotics and sterile gloves during MMS were associated with
      modest reduction of risk for adverse events. CONCLUSIONS AND RELEVANCE: Mohs
      micrographic surgery is safe, with a very low rate of adverse events, an
      exceedingly low rate of serious adverse events, and an undetectable mortality
      rate. Common complications include infections, followed by impaired wound healing
      and bleeding. Bleeding and wound-healing issues are often associated with
      preexisting anticoagulation therapy, which is nonetheless managed safely during
      MMS. We are not certain whether the small effects seen with the use of sterile
      gloves and antiseptics and antibiotics are clinically significant and whether
      wide-scale practice changes would be cost-effective given the small risk
      reductions.

PMID- 24080871
TI  - The road from AKI to CKD: the role of endothelin.
AB  - The incidence of acute kidney injury (AKI) is increasing. It is now widely
      accepted that patients surviving an episode of AKI have a significant risk of
      progression to chronic kidney disease (CKD) and even end-stage renal failure.
      Zager and colleagues describe the role of endothelin-1 (ET-1) in the progression
      of AKI to CKD and provide a basis for the potential use of ET receptor
      antagonists as a therapeutic strategy in AKI. 

PMID- 24080872
TI  - Dietary phosphate: the challenges of exploring its role in FGF23 regulation.
AB  - Fibroblast growth factor 23 (FGF23) is an important regulator of phosphate
      homeostasis, yet efforts to control its circulating levels by manipulating
      dietary phosphate intake in humans and animals with normal or impaired kidney
      function have yielded conflicting results. In the study by Zhang et al., severe
      phosphate restriction in a genetic mouse model of progressive kidney dysfunction
      failed to cause a uniform FGF23 reduction, again highlighting the complexity of
      FGF23 regulation. 

PMID- 24080873
TI  - Peri-dialytic hypertension and hypotension: another U-shaped BP-outcome
      association.
AB  - Park et al. performed a retrospective analysis of a large hemodialysis cohort to
      describe the relationship between pre- to postdialysis changes in BP and
      mortality. Their study demonstrated adverse outcomes associated both with large
      decreases and with any increase in blood pressure pre- to postdialysis. Although
      limitations exist in this analysis, which lacked intradialytic blood pressure
      measurements, the results support the ongoing concern about the potential adverse
      hemodynamic stress associated with conventional three-times-weekly hemodialysis. 

PMID- 24080874
TI  - Biomarkers and creatinine in AKI: the trough of disillusionment or the slope of
      enlightenment?
AB  - Assessment of acute kidney biomarkers against changes in plasma creatinine is
      beset by issues of heterogeneity of study cohorts and timing of sampling. Siew
      and colleagues attempt to minimize these issues in a case-control study of three
      biomarkers in the intensive care unit. The results highlight the inherent
      methodological difficulties and the need to reference structural injury
      biomarkers against more meaningful outcomes. 

PMID- 24080875
TI  - Does equal care give equal outcomes?
AB  - Kidney transplant recipients of lower socioeconomic status (SES) or from lower
      SES areas have comparatively poor graft survival. Whether this results in poorer
      patient survival after kidney transplantation was largely unknown. Begaj et al.
      demonstrate that kidney transplant recipients from deprived areas have higher
      mortality than patients from more advantaged areas in England. We found similar
      patterns in Australia. If such disparities are to be addressed, a better
      understanding of the mediating factors is required. 

PMID- 24080876
TI  - Predicting long-term outcome in renal transplantation.
AB  - Long-term outcome in renal transplantation is heterogeneous, and predicting
      success is challenging. Astor and colleagues report that serum beta2M levels
      measured on discharge after transplantation correlate closely with long-term
      patient and graft survival, and may serve as a biomarker of clinical risk. beta2M
      may provide a more precise measurement of glomerular filtration, combined with an
      index of inflammatory burden related to rejection or systemic vascular disease.
      Association must not be confused with prediction, however, and the role of beta2M
      must be tested in a validation cohort to define sensitivity, specificity and
      predictive performance at the individual, rather than the population, level. 

PMID- 24080877
TI  - The authors reply:.

PMID- 24080878
TI  - Do fluctuations in plasma creatinine/estimated glomerular filtration rate
      represent a risk factor for mortality?

PMID- 24080879
TI  - The authors reply:.

PMID- 24080880
TI  - Left ventricular hypertrophy and serum phosphate in peritoneal dialysis patients.

PMID- 24080881
TI  - Cutaneous fistula from obstructive pyelonephritis.

PMID- 24080882
TI  - The case: fever, skin lesion, and acute renal failure.

PMID- 24080883
TI  - Update on the use of direct-acting antiviral agents for the treatment of chronic
      hepatitis C virus infection.

PMID- 24080884
TI  - Identification of fungal clinical isolates by matrix-assisted laser desorption
      ionization-time-of-flight mass spectrometry.
AB  - BACKGROUND: Recently, bacterial identification by MALDI-TOF MS has acquired a
      high relevance in terms of speed and reliability. Conventional mycological
      identification has some disadvantages: it is frequently slow, reliability is
      sometimes low, and an extensive experience is required. The risk population for
      fungal infections, and therefore their clinical significance has progressively
      increased in recent years. METHODS: 153 yeast and mould clinical isolates were
      analyzed by MALDI-TOF MS and conventional identification. When both methods were
      discrepant to the genus or species level, ITS-2 sequencing was performed.
      Results. The correlation in yeasts identification between conventional
      identification methods and MALDI-TOF MS was extremely high (99.2% to the species
      level and 100% to the genus level). The only discrepancy was checked by ITS-2
      sequencing and confirmed the MALDI-TOF identification. The correlation in moulds
      identification was more heterogeneous. 68.7% of the isolates showed correlation
      at least to the genus level and 40.6% to the species level. Therefore, the
      correlation between conventional identification and MALDI-TOF MS in fungal
      identification was, in whole, 87% to the species level, and 93.5% to the genus
      level. CONCLUSIONS: Identification of fungi by MALDI-TOF MS is reliable and shows
      potential advantages over conventional identification methods.

PMID- 24080885
TI  - [Psoas abscess associated with hip arthroplasty infection].
AB  - INTRODUCTION: Psoas abscess associated with hip arthroplasty infection is a rare
      entity. The aim of this report was to review our experience. MATERIAL AND
      METHODS: Patients with computerized tomography (CT) diagnosis of psoas abscess
      associated with a hip arthroplasty infection from 2004 to 2009 were
      retrospectively reviewed. Demographics, microbiological data, CT results and
      outcome of each patient were recorded. RESULTS: Seven patients out of 214
      evaluated by CT due to hip infection suspected were identified. Three women and 4
      men, with a mean age of 69 years (range 46-89). Mean abscess diameter was of 62 x
      47 mm. In all cases, a direct communication between abscess and prosthesis was
      observed. The most commonly isolated microorganisms were grampositive cocci. All
      patients were treated with two-stage revision surgery. After a mean follow-up of
      65 months (28-113), six patients were in remission. CONCLUSIONS: The use of CT in
      the study of suspected infection of a hip arthroplasty identified a psoas abscess
      in 7 cases out of 214 evaluated. Patients treated with two-stage revision surgery
      and large debridement was associated with a good clinical outcome.

PMID- 24080886
TI  - [Study of a cohort of patients with Enterococcus spp. Bacteraemia. Risk factors
      associated to high-level resistance to aminoglycosides].
AB  - OBJECTIVES: To analyze a cohort of patients with Enterococcus sp. bacteraemia.
      PATIENTS AND METHODS: Retrospective and observational study of a cohort of non
      pediatric in-patients with Enterococcus spp. bacteraemia (June 2007-September
      2009). Data collection from clinical records was done according to a standard
      protocol. We analyzed epidemiological, clinical and microbiological data.
      Treatment with glycopeptides in non allergic patients or in case of betalactam
      susceptibility (ampicillin) was considered "optimizable". RESULTS: Three were 106
      cases of bacteraemia (2.2/1000 admitted patients; 84% E. faecalis); 83% had an
      underlying condition; 88% nosocomial or health related cases. Urinary infection
      was present in 20% and primary bacteraemia in 47%. High level resistance to
      gentamicin (HLRG) was present in 60%; there was no vancomycin or linezolid
      resistance. Most frequent empiric treatments were penicillin-betalactamase
      inhibitor (25%) and glycopeptides (22%). Most frequent definitive treatment was
      glycopeptides (34%), being "optimized" 21% and 44% of empiric and definitive
      treatments, respectively. Mortality was 23% (related, 14%). In the multivariate
      analysis, risk factors associated with HLRG were nosocomial acquired infection
      (OR 6.083; 95CI% 1.428-25.915) and no-abdominal origin (OR 6.006; 95CI%1.398
      25.805). In multivariate analysis, independent risk factors for mortality were:
      Pitt > 3 (OR 14.405; 95CI%2.236-92.808) and active empiric treatment (OR 8.849;
      95CI% 1.101-71.429). Incidence in previous cohort was similar but HLRG rate has
      increased. CONCLUSIONS: Risk factors associated with HLRG were nosocomial
      acquired infection and no-abdominal origin. Risk factors for mortality were
      initial clinical severity and having received active empiric treatment. HLRG rate
      has increased.

PMID- 24080887
TI  - [Structural dynamics of Legionella pneumophila and Legionella bozemanii
      colony/biofilm].
AB  - OBJECTIVES: The genus Legionella includes very pleomorphic species responsible
      for disease outbreaks in humans. The appearance of such has great importance to
      develop artificial biofilms in aquatic ecosystems. The aim of this work was to
      study the dynamics of growth and evolution of the internal structure of colonies
      of representative species of the genus as static biofilm model. METHODS: Isolated
      colonies of Legionella pneumophila and Legionella bozemanii grown in specific
      media for three and fifteen days were processed for histological methods and
      embedded in paraffin and epoxy resin for analysis by light microscopy, electron
      microscopy and image analysis. RESULTS. In colonies of both species were observed
      and defined specific architectural patterns, based on stratification and evolve
      over time. The strata differ in the amount of extracellular matrix, the
      morphology and population density and the proportion of dead cells. The internal
      structure of three days colonies showed large differences between L. pneumophila
      (two layers) and L. bozemanii (four layers). However, in the fifteen days
      colonies of both species evolved towards a common unique pattern formed by three
      layers. In both species the growth was also found within the culture medium,
      although this phenomenon was more intense in L. bozemanii with unique, central
      and larger invasions. CONCLUSIONS: Our results demonstrate that Legionella
      colonies on solid culture media are a good model of static biofilm with a complex
      structural dynamics characterized by the presence of morphological and functional
      subpopulations. We bring here an histological approach model, allowing, in
      further research, detailed studies in evolutionary adaptations in multicellular
      communities to adverse media and to antimicrobials in Legionella species of
      clinical interest.

PMID- 24080888
TI  - Protection of Enterococcus faecalis in mixed cultures with carbapenemase
      producing Escherichia coli and Bacteroide fragilis: effect of the bacterial load.
AB  - INTRODUCTION: This study explores effects of pH and inoculum size on imipenem
      versus tigecycline activity against E. coli, B. fragilis and E. faecalis, both in
      individual and mixed cultures. METHODS: MIC/MBCs (mg/L) of tigecycline and
      imipenem were 0.12/>= 16 and 4/4 for E. coli, 0.12/0.5 and >= 16/>= 16 for B.
      fragilis, and 0.12/>= 16 and 2/>= 16 for E. faecalis, respectively. Killing
      curves in supplemented Brucella broth were performed at pH 7 or 5.8, with two
      final inocula (~ 105 or ~ 107 cfu/ml) of each isolate (individual cultures) and
      with 1:1:1 mixed inocula. Tubes were 48 h incubated at 37 oC in anaerobiosis.
      Final concentrations (estimated concentrations in colon) were 1.50 mg/L for
      tigecycline and 26.40 mg/L for imipenem, with antibiotic-free curves as controls.
      Experiments were performed in triplicate. RESULTS: Imipenem showed inoculum
      effect against E.coli and B. fragilis, with reductions in initial inocula in
      experiments with standard inocula contrasting with increases in experiments with
      high inocula (both individual and mixed cultures). Against E. faecalis no
      inoculum effect for imipenem was observed in individual cultures, with marked
      reductions in initial inocula regardless inoculum size. However in mixed
      experiments the indirect protection of E. faecalis by the two gramnegatives
      resulted in bacterial regrowth. This protection was inoculum-dependant since it
      occurred with high but not with standard inocula. Tigecycline reduced initial
      inocula of the three isolates regardless culture type (individual/mixed) or
      experimental conditions (pH/inocula size), with lower reductions for the tolerant
      E. faecalis. CONCLUSION: Carbapenemase activity was inoculum-dependant for self
      protection and indirect protection of E. faecalis.

PMID- 24080889
TI  - [Kluyvera ascorbata bacteremia in an adult patient].

PMID- 24080890
TI  - [Anomalous serological pattern of hepatitis B virus in 2 patients treated with
      alemtuzumab].

PMID- 24080891
TI  - [Presumptive identification of Candida albicans based on colony morphology on
      chocolate agar].

PMID- 24080892
TI  - [Consensus document on pneumococcal vaccination in adults with risk underlying
      clinical conditions].

PMID- 24080893
TI  - [Control of Chagas disease in pregnant Latin-American women and her children].
AB  - Chagas disease is a chronic and systemic infection caused by Trypanosoma cruzi.
      According to estimates from WHO, 10 million people are affected by this parasite.
      In the last years, birthrate among the immigrant women from Latin America settled
      in the Comunidad Autonoma de Madrid has been increasing, and as T. cruzi can be
      transmitted from mother to child, in fact 11 cases of congenital Chagas disease
      have been confirmed. Therefore, the aim of this paper is encouraging improvements
      in the coverage of the anti-T. cruzi antibodies detection in pregnant women from
      endemic areas. By this strategy, an active search for infected pregnant women and
      early detection of her infected newborns could be conducted, and then an early
      specific treatment could be administrated. Thus, there could be an important
      contribution to the control of Chagas disease in non-endemic area. 

PMID- 24080896
TI  - Can the calcium hypothesis explain synaptic loss in Alzheimer's disease?
AB  - Alzheimer's disease (AD) is the threat of modern humankind that is provoked by
      increased human lifespan. Despite extensive studies on AD pathology for more than
      100 years, there are no disease-preventing therapies. Growing evidence suggests
      the role of calcium (Ca2+) in the pathogenesis of AD. The main purpose of the
      article is to understand whether modern science is able to explain the synapse
      loss observed in early AD and discuss the role of Ca2+ hypothesis in it. Based on
      results obtained in our laboratory and others, we propose that familial AD
      associated mutations in presenilins cause a Ca2+ overload of endoplasmic
      reticulum stores which leads to compensatory downregulation of the neuronal store
      operated Ca2+ (nSOC) entry pathway. We propose that synaptic nSOC is necessary
      for the stability of mature synaptic spines and that dysfunction of this pathway
      may play an important role in synaptic and memory loss in AD.

PMID- 24080895
TI  - Elevated antisaccade error rate as an intermediate phenotype for psychosis across
      diagnostic categories.
AB  - BACKGROUND: Elevated antisaccade error rate, reflecting problems with inhibitory
      behavioral control, is a promising intermediate phenotype for schizophrenia.
      Here, we consider whether it marks liability across psychotic disorders via
      common or different neurophysiological mechanisms and whether it represents a
      neurocognitive risk indicator apart from the generalized cognitive deficit.
      METHODS: Schizophrenia (n = 267), schizoaffective (n = 150), and psychotic
      bipolar (n = 202) probands, their first-degree relatives (ns = 304, 193, 242,
      respectively), and healthy controls (n = 244), participating in the Bipolar
      Schizophrenia Network on Intermediate Phenotypes consortium, performed
      antisaccade and prosaccade tasks and completed a neuropsychological battery.
      RESULTS: Antisaccade error rate was elevated in proband groups with greatest
      deficit observed in schizophrenia and was unrelated to symptoms and antipsychotic
      treatment. Increased error rate was also observed among relatives, even those
      without history of psychosis or psychosis spectrum personality traits. Relatives'
      deficits were similar across proband diagnoses. Error rate was familial and
      remained elevated in proband and relative groups after accounting for generalized
      cognitive impairment. Speed of attentional shifting, indexed by prosaccade
      latency, was similarly influenced in all groups by manipulations that freed vs
      increasingly engaged attention systems and was inversely associated with
      antisaccade error rate in all but schizophrenia probands. CONCLUSIONS: These
      findings indicate that elevated antisaccade error rate represents an intermediate
      phenotype for psychosis across diagnostic categories, and that it tracks risk
      beyond that attributable to the generalized cognitive deficit. The greater
      severity of antisaccade impairment in schizophrenia and its independence from
      attention shifting processes suggest more severe and specific prefrontal
      inhibitory control deficits in this disorder.

PMID- 24080897
TI  - A prospective, comparative, observational study on optical coherence tomography
      of the anterior eye segment.
AB  - BACKGROUND: We compared two commercially available spectral-domain optical
      coherence tomography (OCT) devices according to their capacity of imaging the
      anterior segment of the eye with the same detail and quality. METHODS: A
      prospective, observational, single-visit study with individuals aged 18 years and
      older was conducted on two different OCT devices: the SpectralisTM OCT and the
      RTVueTM OCT. The resulting OCT images of both study devices of each study subject
      were compared and qualified by a single investigator according to the
      identification of corresponding structures and pathologies (primary endpoint) and
      the comparability of the clinical information given (secondary endpoint).
      RESULTS: We included 28 eyes (28 patients) in our study, e.g. 8 normal eyes, 7 of
      subjects with corneal disease, 8 eyes with chamber angle pathology and 5 cases
      with pathology of the sclera. Of all anterior segment structures analyzed, 93.9%
      were identified by SpectralisTM OCT and 91.2% were detected by RTVue(r) OCT with
      a high positive correlation (r = 0.996; p < 0.0001) between the two devices.
      CONCLUSIONS: The majority of clinically relevant structures could be identified
      with both devices in all subjects. The Spectralis OCT tended to perform better in
      the illustration of deep anterior segment structures like the ciliary body and
      sclera.

PMID- 24080898
TI  - Hypothalamic and pituitary clusterin modulates neurohormonal responses to stress.
AB  - Clusterin is a sulfated glycoprotein abundantly expressed in the pituitary gland
      and hypothalamus of mammals. However, its physiological role in neuroendocrine
      function is largely unknown. In the present study, we investigated the effects of
      intracerebroventricular (ICV) administration of clusterin on plasma pituitary
      hormone levels in normal rats. Single ICV injection of clusterin provoked
      neurohormonal changes seen under acute stress condition: increased plasma
      adrenocorticotropic hormone (ACTH), corticosterone, GH and prolactin levels and
      decreased LH and FSH levels. Consistently, hypothalamic and pituitary clusterin
      expression levels were upregulated following a restraint stress, suggesting an
      involvement of endogenous clusterin in stress-induced neurohormonal changes. In
      the pituitary intermediate lobe, clusterin was coexpressed with
      proopiomelanocortin (POMC), a precursor of ACTH. Treatment of clusterin in POMC
      expressing AtT-20 pituitary cells increased basal and corticotropin-releasing
      hormone (CRH)-stimulated POMC promoter activities and intracellular cAMP levels.
      Furthermore, clusterin treatment triggered ACTH secretion from AtT-20 cells in a
      CRH-dependent manner, indicating that increased clusterin under stressful
      conditions may augment CRH-stimulated ACTH production and release. In summary,
      hypothalamic and pituitary clusterin may function as a modulator of neurohormonal
      responses under stressful conditions.

PMID- 24080900
TI  - Soggy-sand electrolytes: status and perspectives.
AB  - Soggy-sand electrolytes (solid-liquid composites, typically gel electrolytes,
      with synergistic electrical properties) are reviewed as far as status and
      perspectives are concerned. Major emphasis is put on the understanding of the
      local mechanism as well as the long-range transport along the filler network. The
      beneficial property spectrum includes enhanced conductivity of one ion type and
      decreased conductivity of the counter ion, but also the exciting mechanical
      properties of the solid-liquid composites. Inherent but not insurmountable
      problems lie in the reproducibility and stationarity of the composites
      microstructure and morphology. Owing to the huge parameter complexity and hence
      to the multitude of adjusting screws, there are various strategies for materials
      optimization. The technological relevance is enormous, in particular for battery
      electrolytes as here all the above-mentioned electrical and mechanical benefits
      are welcome. The soggy-sand electrolytes combine high Li(+) conductivity, low
      anion conductivity and good wettability of electrode particles with the
      mechanical stability of semi-solids. 

PMID- 24080894
TI  - The situation and management of Clostridium difficile infection in Spain: an
      opinion document.

PMID- 24080899
TI  - Increased levels of serum IL-18 are associated with the long-term outcome of
      severe traumatic brain injury.
AB  - OBJECTIVE: A long-lasting neuroinflammatory cascade may lead to the progression
      of brain damage, favoring neurodegeneration and cognitive impairment in patients
      with traumatic brain injury (TBI), but the potential mechanisms underlying this
      sequence of events remain elusive. Here we aimed to evaluate the impact of
      interleukin (IL)-18, a proinflammatory cytokine elevated in post-acute head
      injury and associated with neurodegeneration, on the long-term outcome of
      patients with chronic TBI. METHODS: The serum content of IL-18 was evaluated in
      16 patients with severe TBI, during their rehabilitation phase, and in a matched
      group of 16 healthy controls. The disability of the enrolled patients was
      evaluated by means of the Glasgow Outcome Scale, Levels of Cognitive Functioning,
      and the Disability Rating Scale. RESULTS: The circulating levels of IL-18 were
      significantly increased in chronic TBI patients, as compared to healthy subjects,
      and correlated with the patients' cognitive impairment and disability severity.
      CONCLUSIONS: IL-18 may contribute to the long-term outcome and neurodegeneration
      in TBI patients. Even though further studies are needed to understand the
      molecular mechanisms underlying the effects of IL-18 on TBI progression and its
      associated drop in cognitive function, a possible role of this cytokine as a
      therapeutic target in TBI can be envisaged.

PMID- 24080901
TI  - Relevant aspects of radiation protection in oil and gas well logging.
AB  - Radiation sources have being widely used in industrial applications, but their
      inappropriate use presents a large potential for hazards to human health and the
      environment. These hazards can be minimised by development of specific radiation
      protection rules and adequate procedures for the handling, use and storage of
      radiation sources, which should be established in a national normative framework.
      Recently, due to discovery of new oil and gas reservoirs on the Brazilian
      continental shelf, especially in deep water and the pre-salt layer, there has
      been a large and rapid increase in the use of radiation sources for well logging.
      Generic radiation protection regulations have been used for licensing the use of
      radiation sources for well logging, but these are not comprehensive or
      technically suitable for this purpose. Therefore it is necessary to establish
      specific Brazilian safety regulations for this purpose. In this work, an
      assessment is presented of the relevant radiation protection aspects of nuclear
      well logging not covered by generic regulations, with the aim of contributing to
      the future development of specific safety regulations for the licensing of
      radioactive facilities for oil and gas well logging in Brazil. The conclusions of
      this work relate to four areas, which include the specific requirements to
      control (1) radiation sources, (2) radiation survey meters and (3) access to
      radiation workplaces and (4) to control and identify the workers who are
      occupationally exposed. 

PMID- 24080902
TI  - Bed sharing per se is not dangerous.

PMID- 24080903
TI  - Paediatric urology: the milky way to prevent neonatal bladder infection.

PMID- 24080904
TI  - Urinary incontinence in children with special needs.
AB  - Nocturnal enuresis, daytime urinary incontinence, lower urinary tract symptoms
      and faecal incontinence are more common in children with special needs than in
      typically developing children. Children with intellectual disability, which can
      be attributed to a range of causes, are particularly affected. Indeed, the
      epidemiological and clinical studies conducted to date show clear associations
      that children with special needs have higher rates of urinary (and faecal)
      incontinence than children without development, physical or cognitive
      impairments. For example, low intelligence quotient (IQ)-associated physical
      disability and conditions such as Fragile X and Rett syndromes increase the risk
      for incontinence, which can persist into adulthood if left untreated. Although
      the association of attention deficit hyperactivity disorder and incontinence has
      been shown in many studies, further research is needed on other specific
      disorders, such as autism. As many children are not receiving adequate care,
      specific multimodal treatments based on rigorous assessment of the incontinence,
      underlying condition and associated comorbid disorders should be actively
      offered. 

PMID- 24080905
TI  - Paediatric urology: invasive management needed for failed pyeloplasty?

PMID- 24080906
TI  - Bladder cancer: mutation found in >70% of tumours.

PMID- 24080907
TI  - Hostility, health behaviors, and risk of recurrent events in patients with stable
      coronary heart disease: findings from the Heart and Soul Study.
AB  - BACKGROUND: Hostility is a significant predictor of mortality and cardiovascular
      events in patients with coronary heart disease (CHD), but the mechanisms that
      explain this association are not well understood. The purpose of this study was
      to evaluate potential mechanisms of association between hostility and adverse
      cardiovascular outcomes. METHODS AND RESULTS: We prospectively examined the
      association between self-reported hostility and secondary events (myocardial
      infarction, heart failure, stroke, transient ischemic attack, and death) in 1022
      outpatients with stable CHD from the Heart and Soul Study. Baseline hostility was
      assessed using the 8-item Cynical Distrust scale. Cox proportional hazard models
      were used to determine the extent to which candidate biological and behavioral
      mediators changed the strength of association between hostility and secondary
      events. During an average follow-up time of 7.4 +/- 2.7 years, the age-adjusted
      annual rate of secondary events was 9.5% among subjects in the highest quartile
      of hostility and 5.7% among subjects in the lowest quartile (age-adjusted hazard
      ratio [HR]: 1.68, 95% confidence interval [CI]: 1.30 to 2.17; P < 0.0001). After
      adjustment for cardiovascular risk factors, participants with hostility scores in
      the highest quartile had a 58% greater risk of secondary events than those in the
      lowest quartile (HR: 1.58, 95% CI: 1.19 to 2.09; P = 0.001). This association was
      mildly attenuated after adjustment for C-reactive protein (HR: 1.41, 95% CI, 1.06
      to 1.87; P = 0.02) and no longer significant after further adjustment for smoking
      and physical inactivity (HR: 1.25, 95% CI: 0.94 to 1.67; P = 0.13). CONCLUSIONS:
      Hostility was a significant predictor of secondary events in this sample of
      outpatients with baseline stable CHD. Much of this association was moderated by
      poor health behaviors, specifically physical inactivity and smoking.

PMID- 24080908
TI  - The origin of human mesenchymal stromal cells dictates their reparative
      properties.
AB  - BACKGROUND: Human mesenchymal stromal cells (hMSCs) from adipose cardiac tissue
      have attracted considerable interest in regard to cell-based therapies. We aimed
      to test the hypothesis that hMSCs from the heart and epicardial fat would be
      better cells for infarct repair. METHODS AND RESULTS: We isolated and grew hMSCs
      from patients with ischemic heart disease from 4 locations: epicardial fat,
      pericardial fat, subcutaneous fat, and the right atrium. Significantly, hMSCs
      from the right atrium and epicardial fat secreted the highest amounts of trophic
      and inflammatory cytokines, while hMSCs from pericardial and subcutaneous fat
      secreted the lowest. Relative expression of inflammation- and fibrosis-related
      genes was considerably higher in hMSCs from the right atrium and epicardial fat
      than in subcutaneous fat hMSCs. To determine the functional effects of hMSCs, we
      allocated rats to hMSC transplantation 7 days after myocardial infarction. Atrial
      hMSCs induced greatest infarct vascularization as well as highest inflammation
      score 27 days after transplantation. Surprisingly, cardiac dysfunction was worst
      after transplantation of hMSCs from atrium and epicardial fat and minimal after
      transplantation of hMSCs from subcutaneous fat. These findings were confirmed by
      using hMSC transplantation in immunocompromised mice after myocardial infarction.
      Notably, there was a correlation between tumor necrosis factor-alpha secretion
      from hMSCs and posttransplantation left ventricular remodeling and dysfunction.
      CONCLUSIONS: Because of their proinflammatory properties, hMSCs from the right
      atrium and epicardial fat of cardiac patients could impair heart function after
      myocardial infarction. Our findings might be relevant to autologous mesenchymal
      stromal cell therapy and development and progression of ischemic heart disease.

PMID- 24080909
TI  - Repetitive myocardial ischemia promotes coronary growth in the adult mammalian
      heart.
AB  - BACKGROUND: Coronary artery disease and ischemic cardiomyopathy represent the
      leading cause of heart failure and continue to grow at exponential rates. Despite
      widespread availability of coronary bypass surgery and percutaneous coronary
      intervention, subsequent ischemic events and progression to heart failure
      continue to be common occurrences. Previous studies have shown that a subgroup of
      patients develop collateral blood vessels that serve to connect patent and
      occluded arteries and restore perfusion to ischemic territories. The presence of
      coronary collaterals has been correlated with improved clinical outcomes;
      however, the molecular mechanisms governing this process remain largely unknown.
      METHODS AND RESULTS: To date, no mouse models of coronary arterial growth have
      been described. Using a closed-chest model of myocardial ischemia, we have
      demonstrated that brief episodes of repetitive ischemia are sufficient to promote
      the growth of both large coronary arteries and the microvasculature. Induction of
      large coronary artery and microvascular growth resulted in improvements in
      myocardial perfusion after prolonged ischemia and protected from subsequent
      myocardial infarction. We further show that repetitive ischemia did not lead to
      increased expression of classic proangiogenic factors but instead resulted in
      activation of the innate immune system and recruitment of macrophages to growing
      blood vessels. CONCLUSIONS: These studies describe a novel model of coronary
      angiogenesis and implicate the cardiac macrophage as a potential mediator of
      ischemia-driven coronary growth.

PMID- 24080910
TI  - Conditional knockout of myocyte focal adhesion kinase abrogates ischemic
      preconditioning in adult murine hearts.
AB  - BACKGROUND: Our laboratory has previously demonstrated the importance of a
      cytoskeletal-based survival signaling pathway using in vitro models of
      ischemia/reperfusion (IR). However, the importance of this pathway in mediating
      stress-elicited survival signaling in vivo is unknown. METHODS AND RESULTS: The
      essential cytoskeletal signaling pathway member focal adhesion kinase (FAK) was
      selectively deleted in adult cardiac myocytes using a tamoxifen-inducible Cre-Lox
      system (alpha-MHC-MerCreMer). Polymerase chain reaction (PCR) and Western blot
      were performed to confirm FAK knockout (KO). All mice were subjected to a 40
      minute coronary occlusion followed by 24 hours of reperfusion. Ischemic
      preconditioning (IP) was performed using a standard protocol. Control groups
      included wild-type (WT) and tamoxifen-treated alpha-MHC-MerCreMer+/-/FAK(WT/WT)
      (experimental control) mice. Infarct size was expressed as a percentage of the
      risk region. In WT mice IP significantly enhanced the expression of
      activated/phosphorylated FAK by 36.3% compared to WT mice subjected to a sham
      experimental protocol (P <= 0.05; n = 6 hearts [sham], n = 4 hearts [IP]). IP
      significantly reduced infarct size in both WT and experimental control mice
      (43.7% versus 19.8%; P <= 0.001; 44.7% versus 17.5%; P <= 0.001, respectively).
      No difference in infarct size was observed between preconditioned FAK KO and
      nonpreconditioned controls (37.1% versus 43.7% versus 44.7%; FAK KO versus WT
      versus experimental control; P=NS). IP elicited a 67.2%/88.8% increase in
      activated phosphatidylinositol-3-kinase (PI3K) p85/activated Akt expression in WT
      mice, but failed to enhance the expression of either in preconditioned FAK KO
      mice. CONCLUSIONS: Our results indicate that FAK is an essential mediator of IP
      elicited cardioprotection and provide further support for the hypothesis that
      cytoskeletal-based signaling is an important component of stress-elicited
      survival signaling.

PMID- 24080914
TI  - Racial differences in attitudes toward personalized medicine.
AB  - BACKGROUND/AIMS: Patient concerns regarding personalized medicine may limit its
      use. This study assesses racial differences in attitudes toward personalized
      medicine, evaluating variables that may influence these attitudes. METHODS: A
      convenience sample of 190 adults (>=18 years) from an academic primary care
      practice was surveyed regarding awareness and acceptance of personalized
      medicine, plus concerns and benefits regarding its use. Logistic regressions
      predicting awareness, acceptance and concerns were performed, controlling for
      race, gender, marital status, education, children, internet use, and self
      reported discrimination. RESULTS: The sample was 35% non-Hispanic white (NHW) and
      34.7% male. More NHW participants expressed acceptance of personalized medicine
      than non-Hispanic black (NHB) participants (94.4 vs. 81.9%, p = 0.0190). More
      NHBs were concerned about the use of genes without consent (57.3 vs. 20.6%, p <
      0.0001), sharing genetic information without consent (65.0 vs. 35.6%, p <
      0.0001), discrimination based on genes (62.4 vs. 34.3%, p = 0.0002), and lack of
      access due to cost (75.0 vs. 48.0%, p = 0.0002). In logistic regressions, NHBs
      (OR = 7.46, 95% CI = 3.04-18.32) and those self-reporting discrimination (OR =
      2.87, 95% CI = 1.22-6.78) had more concerns about the misuse of genes and costs
      associated with personalized medicine. CONCLUSION: Racial differences exist in
      attitudes toward personalized medicine and may be influenced by self-reported
      discrimination. Further study to understand factors influencing the acceptance of
      personalized medicine could help encourage its use.

PMID- 24080913
TI  - In vivo pulsed magneto-motive ultrasound imaging using high-performance
      magnetoactive contrast nanoagents.
AB  - Previously, pulsed magneto-motive ultrasound (pMMUS) imaging has been introduced
      as a contrast-agent-assisted ultrasound-based imaging modality capable of
      visualizing biological events at the cellular and molecular level. In pMMUS
      imaging, a high intensity pulsed magnetic field is used to excite cells or tissue
      labeled with magnetic nanoparticles. Then, ultrasound (US) imaging is used to
      monitor the mechanical response of the tissue to an externally applied magnetic
      field (i.e., tissue displacement). Signal to noise ratio (SNR) in pMMUS imaging
      can be improved by using superparamagnetic nanoparticles with larger saturation
      magnetization. Metal-doped magnetic nanoparticles with enhanced tunable
      nanomagnetism are suitable candidates to improve the SNR and, therefore,
      sensitivity of pMMUS imaging, which is essential for in vivo pMMUS imaging. In
      this study, we demonstrate the capability of pMMUS imaging to identify the
      presence and distribution of zinc-doped iron oxide nanoparticles in live nude
      mice bearing A431 (human epithelial carcinoma) xenograft tumors. 

PMID- 24080911
TI  - The Hippo signaling pathway is required for salivary gland development and its
      dysregulation is associated with Sjogren's syndrome.
AB  - Sjogren's syndrome (SS) is a complex autoimmune disease that primarily affects
      salivary and lacrimal glands and is associated with high morbidity. Although the
      prevailing dogma is that immune system pathology drives SS, increasing evidence
      points to structural defects, including defective E-cadherin adhesion, to be
      involved in its etiology. We have shown that E-cadherin has pivotal roles in the
      development of the mouse salivary submandibular gland (SMG) by organizing apical
      basal polarity in acinar and ductal progenitors and by signaling survival for
      differentiating duct cells. Recently, E-cadherin junctions have been shown to
      interact with effectors of the Hippo signaling pathway, a core pathway regulating
      the organ size, cell proliferation, and differentiation. We now show that Hippo
      signaling is required for SMG-branching morphogenesis and is involved in the
      pathophysiology of SS. During SMG development, a Hippo pathway effector, TAZ,
      becomes increasingly phosphorylated and associated with E-cadherin and alpha
      catenin, consistent with the activation of Hippo signaling. Inhibition of Lats2,
      an upstream kinase that promotes TAZ phosphorylation, results in dysmorphogenesis
      of the SMG and impaired duct formation. SMGs from non-obese diabetic mice, a
      mouse model for SS, phenocopy the Lats2-inhibited SMGs and exhibit a reduction in
      E-cadherin junctional components, including TAZ. Importantly, labial specimens
      from human SS patients display mislocalization of TAZ from junctional regions to
      the nucleus, coincident with accumulation of extracellular matrix components,
      fibronectin and connective tissue growth factor, known downstream targets of TAZ.
      Our studies show that Hippo signaling has a crucial role in SMG-branching
      morphogenesis and provide evidence that defects in this pathway are associated
      with SS in humans. 

PMID- 24080915
TI  - Pure anterograde memory deficit due to secondary lymphoma of the fornix.

PMID- 24080916
TI  - Detecting mood disorder in resource-limited primary care settings: comparison of
      a self-administered screening tool to general practitioner assessment.
AB  - OBJECTIVES: Although efficacious treatments for mood disorders are available in
      primary care, under-diagnosis is associated with under-treatment and poorer
      outcomes. This study compares the accuracy of self-administered screening tests
      with routine general practitioner (GP) assessment for detection of current mood
      disorder. METHODS: 197 consecutive patients attending primary care centres in
      Santiago, Chile enrolled in this cross-sectional study, filling out the Patients
      Health Questionnaire-9 (PHQ-9) for depression and the Mood Disorder Questionnaire
      (MDQ) for bipolar disorder, after routine GP assessment. Diagnostic accuracy of
      these self-administered tools was compared with GP assessment, with gold standard
      diagnosis established by a structured diagnostic interview with trained
      clinicians (SCID-I). RESULTS: The sample was 75% female, with a mean age of 48.5
      (SD 16.8); 37% had a current mood disorder (positive SCID-I result for depression
      or bipolar disorder). Sensitivity of the screening instruments (SI) was
      substantially higher than GP assessment (SI: 0.8, [95% CI 0.71, 0.81], versus GP:
      0.2, [95% CI 0.12, 0.25]: p-value < 0.0001), without sacrifice in specificity
      (SI: 0.9, [95% CI 0.86, 0.96], versus GP: 0.9, [95% CI 0.88, 0.97]: p-value =
      0.7). This led to improvement in both positive predictive value (SI: 0.8, [95% CI
      0.82, 0.90], versus GP: 0.6, [95% CI 0.50, 0.64]: p-value < 0.001) and negative
      predictive value (SI: 0.9, [95% CI 0.78, 0.91] versus GP: 0.7, [95% CI 0.56,
      0.72]: p-value < 0.01). CONCLUSION: Self-administered screening tools are more
      accurate than GP assessment in detecting current mood disorder in low-income
      primary care. Such screening tests may improve detection of current mood disorder
      if implemented in primary care settings.

PMID- 24080918
TI  - Probing secondary coordination sphere influence on the oxygenation of zinc
      alkyls: formation of a unique zinc peroxide species.
AB  - Reactions of ethylzinc derivatives of o-hydroxybiphenyl with O2 were
      investigated. The study revealed an essential role in the oxygenation process of
      intra-molecular interactions involving aromatic rings and provided a unique
      aryloxide (hydroxide) Zn8(OAr)8(OH)6(O2) cluster with an encapsulated peroxide
      species. 

PMID- 24080919
TI  - Clinical, dermoscopic and histopathological features of eccrine poroid neoplasms.
AB  - BACKGROUND: Eccrine poroma (EP) belongs to the group of benign adnexal tumors,
      but cases of eccrine porocarcinoma (EPC) arising on long-standing and untreated
      EP suggest a certain risk of malignant transformation. OBJECTIVES: To describe
      the clinical, dermoscopic and histopathologic features associated with different
      extremes in the spectrum of eccrine poroid neoplasms and to review the according
      literature. METHODS: A retrospective analysis of patient characteristics and
      morphologic features associated with EP, EPC in situ and invasive porocarcinoma
      patients who attended two skin lesion clinics in Italy and Turkey between 2010
      and 2011. RESULTS: A total of 4 cases including 1 EP, 1 EPC in situ and 2 cases
      of invasive EPC in 4 patients were analyzed. Recent changes including bleeding,
      ulceration and sudden enlargement of a pre-existing lesion were associated with
      malignant transformation. Dermoscopically, polymorphous vessels consisting of
      coiled, hairpin and linear vessels were seen at all stages of progression.
      Histopathological findings of EPC in situ were limited to the epidermal component
      and were evident only at higher magnification. CONCLUSIONS: Clinicians and
      pathologists should carefully evaluate EPs with a recent history of change and
      erosion in order to avoid overlooking the potential development of EPC.

PMID- 24080921
TI  - Clay-supported graphene materials: application to hydrogen storage.
AB  - The present work refers to clay-graphene nanomaterials prepared by a green way
      using caramel from sucrose and two types of natural clays (montmorillonite and
      sepiolite) as precursors, with the aim of evaluating their potential use in
      hydrogen storage. The impregnation of the clay substrates by caramel in aqueous
      media, followed by a thermal treatment in the absence of oxygen of these clay
      caramel intermediates gives rise to graphene-like materials, which remain
      strongly bound to the silicate support. The nature of the resulting materials was
      characterized by different techniques such as XRD, Raman spectroscopy and TEM, as
      well as by adsorption isotherms of N2, CO2 and H2O. These carbon-clay
      nanocomposites can act as adsorbents for hydrogen storage, achieving, at 298 K
      and 20 MPa, over 0.1 wt% of hydrogen adsorption excess related to the total mass
      of the system, and a maximum value close to 0.4 wt% of hydrogen specifically
      related to the carbon mass. The very high isosteric heat for hydrogen sorption
      determined from adsorption isotherms at different temperatures (14.5 kJ mol(-1))
      fits well with the theoretical values available for hydrogen storage on materials
      that show a strong stabilization of the H2 molecule upon adsorption. 

PMID- 24080920
TI  - Larotaxel with Cisplatin in the first-line treatment of locally
      advanced/metastatic urothelial tract or bladder cancer: a randomized, active
      controlled, phase III trial (CILAB).
AB  - BACKGROUND: This open-label, randomized phase III trial evaluated
      larotaxel/cisplatin versus gemcitabine/cisplatin as first-line treatment for
      locally advanced (T4b) or metastatic urothelial tract or bladder cancer. METHODS:
      Patients were randomized to larotaxel 50 mg/m(2) with cisplatin 75 mg/m(2) every
      3 weeks (larotaxel/cisplatin) or gemcitabine 1,000 mg/m(2) on days 1, 8, and 15
      with cisplatin 70 mg/m(2) on day 1 every 4 weeks (gemcitabine/cisplatin). The
      primary endpoint was overall survival (OS). RESULTS: The trial was prematurely
      closed following the sponsor's decision to stop clinical development of larotaxel
      (n = 337 randomized). The larotaxel dose was reduced to 40 mg/m(2) and cisplatin
      to 60 mg/m(2) following a data monitoring committee safety review of the first 97
      patients. At the time of analysis, the median OS was 13.7 months [95% confidence
      interval (CI) 11.2-17.1] with larotaxel/cisplatin and 14.3 months (95% CI 10.5 to
      not reached) with gemcitabine/cisplatin [hazard ratio (HR) 1.21; 95% CI 0.83
      1.76; p = 0.33]. The median progression-free survival (PFS) was 5.6 months (95%
      CI 4.1-6.2) with larotaxel/cisplatin and 7.6 months (95% CI 6.6-9.1) with
      gemcitabine/cisplatin (HR 1.67; 95% CI 1.24-2.25). More myelosuppression was
      observed with gemcitabine/cisplatin. CONCLUSION: There was no difference in OS.
      Although the trial was closed prematurely, PFS appeared worse with
      larotaxel/cisplatin, suggesting that larotaxel/cisplatin does not improve
      outcomes versus cisplatin/gemcitabine.

PMID- 24080922
TI  - Why don't dentists provide immunizations?: a missed opportunity.

PMID- 24080923
TI  - Effects of periodontitis.

PMID- 24080924
TI  - Heeding the code.

PMID- 24080925
TI  - Spelling it out.

PMID- 24080926
TI  - The role of the dental profession in addressing the human immunodeficiency virus
      epidemic.

PMID- 24080927
TI  - Hepatitis B virus transmissions associated with a portable dental clinic, West
      Virginia, 2009.
AB  - BACKGROUND: Although hepatitis B virus (HBV) transmission in dental settings is
      rare, in 2009 a cluster of acute HBV infections was reported among attendees of a
      two-day portable dental clinic in West Virginia. METHODS: The authors conducted a
      retrospective investigation by using treatment records and volunteer logs,
      interviews of patients and volunteers with acute HBV infection as well as of
      other clinic volunteers, and molecular sequencing of the virus from those acutely
      infected. RESULTS: The clinic was held under the auspices of a charitable
      organization in a gymnasium staffed by 750 volunteers, including dental care
      providers who treated 1,137 adults. Five acute HBV infections-involving three
      patients and two volunteers-were identified by the local and state health
      departments. Of four viral isolates available for testing, all were genotype D.
      Three case patients underwent extractions; one received restorations and one a
      dental prophylaxis. None shared a treatment provider with any of the others. One
      case volunteer worked in maintenance; the other directed patients from triage to
      the treatment waiting area. Case patients reported no behavioral risk factors for
      HBV infection. The investigation revealed numerous infection control breaches.
      CONCLUSIONS: Transmission of HBV to three patients and two volunteers is likely
      to have occurred at a portable dental clinic. Specific breaches in infection
      control could not be linked to these HBV transmissions. PRACTICAL IMPLICATIONS:
      All dental settings should adhere to recommended infection control practices,
      including oversight; training in prevention of bloodborne pathogens transmission;
      receipt of HBV vaccination for staff who may come into contact with blood or body
      fluids; use of appropriate personal protective equipment, sterilization and
      disinfection procedures; and use of measures, such as high-volume suction, to
      minimize the spread of blood.

PMID- 24080928
TI  - Tooth preservation or implant placement: a systematic review of long-term tooth
      and implant survival rates.
AB  - BACKGROUND: For the past few decades, dental implants have served as reliable
      replacements for missing teeth. However, there is an increasing trend toward
      replacing diseased teeth with dental implants. TYPES OF STUDIES REVIEWED: The
      authors conducted a systematic review of long-term survival rates of teeth and
      implants. They searched the MEDLINE database for relevant publications up to
      March 2013. They considered studies in which investigators assessed the long-term
      effectiveness of dental implants or that of tooth preservation. They included
      only studies that had follow-up periods of 15 years or longer. RESULTS: The
      authors selected 19 articles for inclusion. Investigators in nine studies
      assessed the tooth survival rate, whereas investigators in 10 studies assessed
      the implant survival rate. When comparing the overall long-term (that is, 15
      years or more) tooth loss rate with that of implants, the authors observed rates
      ranging between 3.6 and 13.4 percent and 0 and 33 percent for teeth and implants,
      respectively. They could not perform a meta-analysis because of the substantial
      differences between the studies. PRACTICAL IMPLICATIONS: The results of this
      systematic review show that implant survival rates do not exceed those of
      compromised but adequately treated and maintained teeth, supporting the notion
      that the decision to extract a tooth and place a dental implant should be made
      cautiously. Even when a tooth seems to be compromised and requires treatment to
      be maintained, implant treatment also might require additional surgical
      procedures that might pose some risks as well. Furthermore, a tooth can be
      extracted and replaced at any time; however, extraction is a definitive and
      irreversible treatment.

PMID- 24080929
TI  - Defining and diagnosing burning mouth syndrome: Perceptions of directors of North
      American postgraduate oral medicine and orofacial pain programs.
AB  - BACKGROUND: The authors conducted a study to ascertain participants' perceptions
      of and confidence in their responses regarding the definition and diagnosis of
      burning mouth syndrome (BMS). METHODS: The authors developed an eight-question
      questionaire with input from several experienced clinicians in the fields of oral
      medicine (OM) and orofacial pain (OFP) and sent it to directors (n = 20; OM = 10;
      OFP = 10) of accredited postgraduate training programs in North America. They
      used descriptive statistics to analyze the results. RESULTS: The response rate
      was 65 percent (n = 13; OM = 6; OFP = 7). Participants reported a mean of 7.3
      cases of BMS in any given three-month period, with 89 percent of these cases
      managed within the programs. They identified, with a high degree of confidence,
      overall criteria for establishing a definition and definitive diagnosis of BMS.
      CONCLUSIONS: There were multiple similarities among participants' responses
      regarding the elements to be included in the definition and diagnosis of BMS.
      PRACTICAL IMPLICATIONS: These data provide information on current status of
      definitions and diagnostic guidelines and may assist in development of future
      consensus statements on BMS that incorporate additional geographical
      representation and appropriate methodology.

PMID- 24080930
TI  - Risk of airway embarrassment during root canal therapy.
AB  - BACKGROUND: Root canal therapy (RCT) is a commonly performed dental procedure
      that has a good success rate. Complications of RCT usually are minor, but severe
      complications can occur. CASE DESCRIPTION: A 59-year-old Hispanic man with no
      history of coagulopathy started to hemorrhage profusely from the mesiolingual
      canal of the right mandibular first molar (tooth no. 30) during RCT. The general
      dentist practitioner briefly controlled the hemorrhaging by packing a gutta
      percha point into the mesiolingual canal. Shortly afterward, the patient
      developed an expanding hematoma in the submandibular space. The authors extracted
      tooth no. 30, raised buccal and lingual flaps, and evacuated the hematoma.
      PRACTICAL IMPLICATIONS: It is possible for clinicians to encounter significant
      hemorrhaging and airway compromising swelling when performing root canal therapy.
      Clinicians must recognize and understand how to manage such complications when
      they occur.

PMID- 24080931
TI  - Preventing dental caries associated with sugar-sweetened beverages.
AB  - BACKGROUND: Dietary intake of sugar-sweetened beverages (SSBs) has increased
      during the past 30 years, and SSB intake is associated with caries. CONCLUSIONS:
      SSBs vary in the quantity and nature of sugars they contain; however, all of the
      sugars are fermentable by oral bacteria and potentially cariogenic. PRACTICAL
      IMPLICATIONS: Oral health care practitioners should assess patients' SSB intakes
      by asking questions regarding the quantity, frequency and duration of SSB intake.
      In response to individual behaviors, practitioners should tailor recommendations
      when providing anticipatory guidance to help patients decrease their exposure to
      SSBs for caries prevention. In light of the association between SSB intake and
      caries risk, as well as the increased consumption of SSBs, all dental practices
      should assess patients' SSBs intake.

PMID- 24080932
TI  - A pilot study of a chiropractic intervention for management of chronic myofascial
      temporomandibular disorder.
AB  - BACKGROUND: Temporomandibular pain has multiple etiologies and a range of
      therapeutic options. In this pilot study, the authors assessed the feasibility of
      conducting a larger trial to evaluate chiropractic treatment of temporomandibular
      disorders (TMDs). METHODS: The authors assigned 80 participants randomly into one
      of the following four groups, all of which included a comprehensive self-care
      program: reversible interocclusal splint therapy (RIST), Activator Method
      Chiropractic Technique (AMCT) (Activator Methods International, Phoenix), sham
      AMCT and self-care only. They made assessments at baseline and at month 2 and
      month 6, including use of the Research Diagnostic Criteria for Temporomandibular
      Disorders. RESULTS: The authors screened 721 potential participants and enrolled
      80 people; 52 participants completed the six-month assessment. The adjusted mean
      change in current pain over six months, as assessed on the 11-point numerical
      rating scale, was 2.0 (95 percent confidence interval, 1.1-3.0) for RIST, 1.7
      (0.9-2.5) for self-care only, 1.5 (0.7-2.4) for AMCT and 1.6 (0.7-2.5) for sham
      AMCT. The authors also assessed bothersomeness and functionality. CONCLUSIONS:
      The authors found the study design and methodology to be manageable. They gained
      substantial knowledge to aid in conducting a larger study. AMCT, RIST and self
      care should be evaluated in a future comparative effectiveness study. PRACTICAL
      IMPLICATIONS: This pilot study was a necessary step to prepare for a larger study
      that will provide clinicians with information that should be helpful when
      discussing treatment options for patients with TMD.

PMID- 24080933
TI  - Positive association between conflicts of interest and reporting of positive
      results in randomized clinical trials in dentistry.
AB  - BACKGROUND: The relationship between industry funding and study results has been
      explored widely in medicine but not in dentistry. The authors aimed to assess the
      relationship between conflicts of interest (COIs) and study results. METHODS: The
      authors assessed all randomized clinical trials (RCTs) published between July
      2010 and June 2012 in the 10 dental journals with the highest impact factors in
      dentistry. The authors used three definitions of COI and explored their
      associations with positive study results. RESULTS: Depending on the definition of
      COI, the odds ratio for reporting positive results varied between 2.40 (95
      percent confidence interval [CI], 1.16-5.13) and 9.19 (95 percent CI, 1.71
      170.64). The authors found no association between positive study results and
      journal of publication or area of practice. CONCLUSIONS: RCTs in which authors
      have some type of COI are more likely to have results that support the
      intervention being assessed. PRACTICAL IMPLICATIONS: When reviewing the results
      of RCTs, clinicians need to be aware of the association between reporting
      positive study results and the type of COI disclosure and be even more careful
      when critically appraising and applying their results.

PMID- 24080934
TI  - Coronectomy is an effective strategy for treating impacted third molars in close
      proximity to the inferior alveolar nerve.

PMID- 24080935
TI  - Too many crowns?

PMID- 24080936
TI  - The sustainable dental practice.

PMID- 24080937
TI  - What are my ethical obligations when I learn that my local dental laboratory has
      been subcontracting with offshore laboratories without my knowledge?

PMID- 24080940
TI  - Age sensitivity of NFkappaB abundance and programmed cell death in erythrocytes
      induced by NFkappaB inhibitors.
AB  - BACKGROUND/AIMS: Erythrocytes may enter eryptosis, a suicidal death characterized
      by cell shrinkage and phosphatidylserine exposure at the erythrocyte outer
      membrane. Susceptibility to eryptosis is enhanced in aged erythrocytes and
      stimulated by NFkappaB-inhibitors Bay 11-7082 and parthenolide. Here we explored
      whether expression of NFkappaB and susceptibility to inhibitor-induced eryptosis
      is sensitive to erythrocyte age. METHODS: Human erythrocytes were separated into
      five fractions, based on age-associated characteristics cell density and volume.
      NFkappaB compared to beta-actin protein abundance was estimated by Western
      blotting and cell volume from forward scatter. Phosphatidylserine exposure was
      identified using annexin-V binding. RESULTS: NFkappaB was most abundant in young
      erythrocytes but virtually absent in aged erythrocytes. A 24h or 48h exposure to
      Ringer resulted in spontaneous decrease of forward scatter and increase of
      annexin V binding, effects more pronounced in aged than in young erythrocytes.
      Both, Bay 11-7082 (20 uM) and parthenolide (100 uM) triggered eryptosis, effects
      again most pronounced in aged erythrocytes. CONCLUSION: NFkappaB protein
      abundance is lowest and spontaneous eryptosis as well as susceptibility to Bay 11
      7082 and parthenolide highest in aged erythrocytes. Thus, inhibition of NFkappaB
      signalling alone is not responsible for the stimulation of eryptosis by
      parthenolide or Bay 11-7082.

PMID- 24080941
TI  - Not all "term" infants are created equal.

PMID- 24080942
TI  - Kelvin spray ionization.
AB  - A novel self-powered dual spray ionization source has been developed for
      applications in mass spectrometry. This new source does not use any power supply
      and produces both positive and negative ions simultaneously. The idea behind this
      ionization source comes from the Kelvin water dropper. The source employs one or
      two syringes, two pneumatic sprays operated over a range of flow rates (0.15-15
      MUL min(-1)) and gas pressures (0-150 psi), and two double layered metal screens
      for ion formation. A variable electrostatic potential from 0 to 4 kV can be
      produced depending on solvent and gas flow rates that allow gentle ionization of
      compounds. There are several parameters that affect the performance during
      ionization of molecules including the flow rate of solvent, gas pressure, solvent
      acidity, position of spray and metal screens with respect to each other and
      distance between metal screens and the counter electrode. This ionization method
      has been successfully applied to solutions of peptides, proteins and non-covalent
      complexes. In comparison with ESI, the charge number of the most populated state
      is lower than that from ESI. It indicates that this is a softer ionization
      technique and it produces more protein ions with folded structures. The unique
      features of Kelvin spray ionization (KeSI) are that the method is self-powered
      and ionization occurs at very low potentials by providing very low internal
      energy to the ions. This advantage can be used for the ionization of very fragile
      molecules and investigation of non-covalent interactions. 

PMID- 24080943
TI  - The relationship between 30-year developmental patterns of body fat and body fat
      distribution and its vascular properties: the Amsterdam Growth and Health
      Longitudinal Study.
AB  - INTRODUCTION: Although body fat and body fat distribution are known to be related
      to cardiovascular diseases (CVDs), it is unknown whether specific 30-year
      developmental patterns of body fat are associated with CVDs. This study examines
      the existence of distinct developmental patterns of total fat measured by the sum
      of four skinfolds (S4SFs) and body fat distribution measured by the skinfold
      thickness ratio (SFratio), and relates these patterns to micro- and macrovascular
      functions. METHODS: In 2006, 259 apparently healthy subjects were examined on
      micro- and macrovascular functions, using video microscopy and carotid ultrasound
      sonography. Body fat, using both S4SFs and SFratio, was measured for 10 times
      over 30 years, from 13 years onwards. Latent class growth analyses (LCGA) were
      used to obtain distinct developmental patterns of S4SFs and SFratio. This is a
      data-drive hypothesis-generating approach and could possibly give a new
      perspective on body fatness over time. In addition, a mixed-method approach is
      used to obtain individual growth parameters. Linear regression analyses were used
      to examine the relationship of these patterns and individual growth parameters
      with micro- and macrovascular functions. RESULTS: LCGA identified normal and
      unfavourable developmental patterns in S4SFs and SFratio. Both men and women with
      an unfavourable developmental pattern of S4SFs showed impaired carotid compliance
      (beta=-0.216, P=0.004 and beta=-0.109, P=0.039, respectively), carotid
      distensibility (beta=-5.078, P=0.001 and beta=-5.118, P<0.001, respectively) and
      Young's elastic modulus (beta=0.066, P=0.065 and beta=0.107, P<0.001,
      respectively). In contrast, no relationship for microvascular function with
      developmental patterns of S4SFs was found. Developmental patterns of the SFratio
      were associated with neither measures of micro- nor macrovascular functions. No
      associations were using the individual growth parameters. CONCLUSIONS: For
      macrovascular function, there is a relationship of 30-year developmental patterns
      of S4SFs, whereas no such relationship was found for the 30-year developmental
      patterns of S4SFs or SFratio with microvascular function.

PMID- 24080945
TI  - The elusive path to health care sustainability.

PMID- 24080944
TI  - Lack of functional GABAB receptors alters Kiss1 , Gnrh1 and Gad1 mRNA expression
      in the medial basal hypothalamus at postnatal day 4.
AB  - BACKGROUND/AIMS: Adult mice lacking functional GABAB receptors (GABAB1KO) show
      altered Gnrh1 and Gad1 expressions in the preoptic area-anterior hypothalamus
      (POA-AH) and females display disruption of cyclicity and fertility. Here we
      addressed whether sexual differentiation of the brain and the proper wiring of
      the GnRH and kisspeptin systems were already disturbed in postnatal day 4 (PND4)
      GABAB1KO mice. METHODS: PND4 wild-type (WT) and GABAB1KO mice of both sexes were
      sacrificed; tissues were collected to determine mRNA expression (qPCR), amino
      acids (HPLC), and hormones (RIA and/or IHC). RESULTS: GnRH neuron number (IHC)
      did not differ among groups in olfactory bulbs or OVLT-POA. Gnrh1 mRNA (qPCR) in
      POA-AH was similar among groups. Gnrh1 mRNA in medial basal hypothalamus (MBH)
      was similar in WTs but was increased in GABAB1KO females compared to GABAB1KO
      males. Hypothalamic GnRH (RIA) was sexually different in WTs (males > females),
      but this sex difference was lost in GABAB1KOs; the same pattern was observed when
      analyzing only the MBH, but not in the POA-AH. Arcuate nucleus Kiss1 mRNA
      (micropunch-qPCR) was higher in WT females than in WT males and GABAB1KO females.
      Gad1 mRNA in MBH was increased in GABAB1KO females compared to GABAB1KO males.
      Serum LH and gonadal estradiol content were also increased in GABAB1KOs.
      CONCLUSION: We demonstrate that GABABRs participate in the sexual differentiation
      of the ARC/MBH, because sex differences in several reproductive genes, such as
      Gad1, Kiss1 and Gnrh1, are critically disturbed in GABAB1KO mice at PND4,
      probably altering the organization and development of neural circuits governing
      the reproductive axis.

PMID- 24080948
TI  - Identification of conductive hearing loss using air conduction tests alone:
      reliability and validity of an automatic test battery.
AB  - OBJECTIVES: The primary objective of this study was to determine whether a
      combination of automatically administered pure-tone audiometry and a tone-in
      noise detection task, both delivered via an air conduction (AC) pathway, could
      reliably and validly predict the presence of a conductive component to the
      hearing loss. The authors hypothesized that performance on the battery of tests
      would vary according to hearing loss type. A secondary objective was to evaluate
      the reliability and validity of a novel automatic audiometry algorithm to assess
      its suitability for inclusion in the test battery. DESIGN: Participants underwent
      a series of hearing assessments that were conducted in a randomized order: manual
      pure-tone air conduction audiometry and bone conduction audiometry; automatic
      pure-tone air conduction audiometry; and an automatic tone-in-noise detection
      task. The automatic tests were each administered twice. The ability of the
      automatic test battery to: (a) predict the presence of an air-bone gap (ABG); and
      (b) accurately measure AC hearing thresholds was assessed against the results of
      manual audiometry. Test-retest conditions were compared to determine the
      reliability of each component of the automatic test battery. Data were collected
      on 120 ears from normal-hearing and conductive, sensorineural, and mixed hearing
      loss subgroups. RESULTS: Performance differences between different types of
      hearing loss were observed. Ears with a conductive component (conductive and
      mixed ears) tended to have normal signal to noise ratios (SNR) despite impaired
      thresholds in quiet, while ears without a conductive component (normal and
      sensorineural ears) demonstrated, on average, an increasing relationship between
      their thresholds in quiet and their achieved SNR. Using the relationship between
      these two measures among ears with no conductive component as a benchmark, the
      likelihood that an ear has a conductive component can be estimated based on the
      deviation from this benchmark. The sensitivity and specificity of the test
      battery vary depending on the size of this deviation, but increase with
      increasing ABG size, with decreasing test frequency, and when results from
      multiple test frequencies are taken into account. The individual automatic tests
      comprising the battery were found to be reliable and valid, with strong,
      significant correlations between the test and retest results (r = 0.81 to 0.99; p
      < 0.0001) and between automatic and manual audiometry procedures (r = 0.98 to
      0.99; p < 0.0001). CONCLUSIONS: The presence of an ABG can be predicted with a
      reasonably high degree of accuracy using AC tests alone. Applications of such a
      test battery include any clinical context in which bone conduction audiometry or
      specialized diagnostic equipment is unavailable or impractical. Examples of these
      include self-fitting hearing aids, whose efficacy relies on the ability of the
      device to automatically administer an in situ hearing test; self-administered
      adult hearing screenings in both clinical and home environments; large-scale
      industrial hearing conservation programs; and test environments in which ambient
      noise levels exceed the maximum permissible levels for unoccluded ears.

PMID- 24080946
TI  - Histone deacetylase inhibitors induce apoptosis in myeloid leukemia by
      suppressing autophagy.
AB  - Histone deacetylase (HDAC) inhibitors (HDACis) are well-characterized anti-cancer
      agents with promising results in clinical trials. However, mechanistically little
      is known regarding their selectivity in killing malignant cells while sparing
      normal cells. Gene expression-based chemical genomics identified HDACis as being
      particularly potent against Down syndrome-associated myeloid leukemia (DS-AMKL)
      blasts. Investigating the antileukemic function of HDACis revealed their
      transcriptional and post-translational regulation of key autophagic proteins,
      including ATG7. This leads to suppression of autophagy, a lysosomal degradation
      process that can protect cells against damaged or unnecessary organelles and
      protein aggregates. DS-AMKL cells exhibit low baseline autophagy due to mammalian
      target of rapamycin (mTOR) activation. Consequently, HDAC inhibition repressed
      autophagy below a critical threshold, which resulted in accumulation of
      mitochondria, production of reactive oxygen species, DNA damage and apoptosis.
      Those HDACi-mediated effects could be reverted upon autophagy activation or
      aggravated upon further pharmacological or genetic inhibition. Our findings were
      further extended to other major acute myeloid leukemia subgroups with low basal
      level autophagy. The constitutive suppression of autophagy due to mTOR activation
      represents an inherent difference between cancer and normal cells. Thus, via
      autophagy suppression, HDACis deprive cells of an essential pro-survival
      mechanism, which translates into an attractive strategy to specifically target
      cancer cells. 

PMID- 24080950
TI  - Physical exercise and brain responses to images of high-calorie food.
AB  - Physical exercise has many health benefits, including improved cardiovascular
      fitness, lean muscle development, increased metabolism, and weight loss, as well
      as positive effects on brain functioning and cognition. Recent evidence suggests
      that regular physical exercise may also affect the responsiveness of reward
      regions of the brain to food stimuli. We examined whether the total number of
      minutes of self-reported weekly physical exercise was related to the
      responsiveness of appetite and food reward-related brain regions to visual
      presentations of high-calorie and low-calorie food images during functional MRI.
      Second, we examined whether such responses would correlate with self-reported
      food preferences. While undergoing scanning, 37 healthy adults (22 men) viewed
      images of high-calorie and low-calorie foods and provided desirability ratings
      for each food image. The correlation between exercise minutes per week and brain
      responses to the primary condition contrast (high-calorie>low-calorie) was
      evaluated within the amygdala, insula, and medial orbitofrontal cortex, brain
      regions previously implicated in responses to food images. Higher levels of
      exercise were significantly correlated with lower responsiveness within the
      medial orbitofrontal cortex and left insula to high-calorie foods. Furthermore,
      activation of these regions was positively correlated with preference ratings for
      high-calorie foods, particularly those with a savory flavor. These findings
      suggest that physical exercise may be associated with reduced activation in food
      responsive reward regions, which are in turn associated with reduced preferences
      for unhealthy high-calorie foods. Physical exercise may confer secondary health
      benefits beyond its primary effects on cardiovascular fitness and energy
      expenditure. 

PMID- 24080949
TI  - Cochlear function among HIV-seropositive and HIV-seronegative men and women.
AB  - OBJECTIVES: There is limited research about cochlear function in adults who are
      human immunodeficiency virus (HIV) positive (+). The aim of the present study was
      to collect measures of cochlear function in a large sample of adults with, or at
      risk for, HIV infection, to evaluate associations between HIV status, HIV
      treatment, and cochlear function. DESIGN: Distortion product otoacoustic
      emissions (DPOAEs) were used to evaluate cochlear function in 506 participants;
      329 men, 150 of whom were HIV+, and 177 women, 136 of whom were HIV+. DPOAEs were
      measured at frequencies 1000, 2000, 3000, 4000, and 6000 Hz. A DPOAE nonresponse
      (NR) was defined as an absolute DPOAE level less than -15 dB SPL or a difference
      between the absolute DPOAE level and the background noise level less than 6 dB.
      The total number of NRs was calculated for each ear. The associations of
      demographic variables, HIV status, and HIV treatment with number of NRs were
      evaluated with univariate and multivariate ordinal regression models. RESULTS:
      There was a statistically significant increase in the odds of higher numbers of
      NRs with age, being male, and being non-Black, but not with HIV status. Among
      HIV+ participants, there were no statistically significant associations of the
      HIV disease status or treatment variables with higher number of NRs. CONCLUSION:
      The authors found no evidence of impaired cochlear function by HIV disease status
      or highly active antiretroviral therapy-treated HIV infection in this cross
      sectional study.

PMID- 24080951
TI  - Twenty years of physical mapping of major ribosomal RNA genes across the
      teleosts: A review of research.
AB  - Molecular cytogenetic data on the number and position of 45S ribosomal RNA genes
      (rDNA; located in nucleolus organizing regions, NORs) detected by FISH in 330
      species of 77 families and 22 orders of bony fishes (Teleostei) and,
      additionally, 11 species of basal ray-finned fishes are compiled and analyzed.
      The portion of species with single rDNA sites in the sample amounts to 72%. The
      percentage of species with multiple NORs decreases with increasing numbers of
      rDNA loci per genome, i.e. scarcely 3% of species carry 4 or more rDNA-bearing
      chromosome pairs. 43% of all rDNA sites analyzed occur terminally on the short
      arms of chromosomes or constitute them. In general, terminal rDNA sites account
      for 87% of all examined cases. Interspecific variation in the location of single
      rDNA sites among related taxa, polymorphisms of multiple NORs in some groups of
      teleosts and analytical outcomes on the subject are reviewed.

PMID- 24080952
TI  - Morphosynthesis of cubic silver cages on monolithic activated carbon.
AB  - Cubic silver cages were prepared on monolithic activated carbon (MAC) pre
      absorbed with Cl(-), SO4(2-), or PO4(3-) anions. Silver insoluble salts served as
      templates for the morphosynthesis of silver cages. The silver ions were reduced
      by reductive functional groups on MAC micropores through a galvanic cell reaction
      mechanism. 

PMID- 24080953
TI  - Ischemic stroke in patients with solid gynecologic tract tumors and coagulopathy.
AB  - AIM: Patients with gynecological neoplasms often suffer ischemic stroke. This
      study aimed to clarify the underlying mechanisms of ischemic stroke in patients
      with gynecological tract tumors. METHODS: We retrospectively reviewed 6 patients
      with gynecologic tumors and hypercoagulability who were being treated for acute
      ischemic stroke between 2006 and 2012. Diffusion-weighted magnetic resonance
      imaging (DW-MRI), cardiovascular risk factors including plasma D-dimer levels,
      and histologic examination of the patients' solid tumors were performed. All 6
      patients underwent transesophageal echocardiography (TEE) for nonbacterial
      thrombotic endocarditis (NBTE) and paradoxical embolism. RESULTS: All 6 patients
      showed elevated plasma D-dimer levels. In 1 patient, paradoxical embolism was
      diagnosed. In the remaining 5 patients, DW-MRI scans showed numerous lesions in
      multiple vascular territories, and in 4 of these 5 patients, TEE demonstrated
      vegetations on the mitral valve, leading to the diagnosis of NBTE. Interestingly,
      2 of these 4 patients had benign uterine tumors, whereas the other 2 had ovarian
      cancer. CONCLUSIONS: NBTE was the main etiology for ischemic stroke in patients
      with gynecologic tract tumors and coagulopathy. Both malignant and benign tumors
      of the gynecologic tract can cause NBTE.

PMID- 24080955
TI  - Too much medicine happens too often: the teachable moment and a call for
      manuscripts from clinical trainees.

PMID- 24080956
TI  - Expression of PIK3CA mutant E545K in the mammary gland induces heterogeneous
      tumors but is less potent than mutant H1047R.
AB  - The phosphoinositide 3-kinase (PI3K) signaling cascade is a key mediator of
      cellular growth, survival and metabolism and is frequently subverted in human
      cancer. The gene encoding for the alpha catalytic subunit of PI3K (PIK3CA) is
      mutated and/or amplified in ~30% of breast cancers. Mutations in either the
      kinase domain (H1047R) or the helical domain (E545K) are most common and result
      in a constitutively active enzyme with oncogenic capacity. PIK3CA(H1047R) was
      previously demonstrated to induce tumors in transgenic mouse models; however, it
      was not known whether overexpression of PIK3CA(E545K) is sufficient to induce
      mammary tumors and whether tumor initiation by these two types of mutants
      differs. Here, we demonstrate that expression of PIK3CA(E545K) in the mouse
      mammary gland induces heterogenous mammary carcinomas but with a longer latency
      than PIK3CA(H1047R)-expressing mice. Our results suggest that the helical domain
      mutant PIK3CA(E545K) is a less potent inducer of mammary tumors due to less
      efficient activation of downstream Akt signaling. 

PMID- 24080957
TI  - Cigarette smoking and gemcitabine-induced neutropenia in advanced solid tumors.
AB  - BACKGROUND: Chemotherapy-associated neutropenia has been reported to be a
      pharmacodynamic marker of response in some advanced solid tumors. Factors that
      accelerate drug clearance lead to lower plasma concentrations and toxicity,
      including neutropenia. Smoking accelerates the metabolism of several drugs,
      including chemotherapy. We sought to study the effects of smoking on gemcitabine
      induced neutropenia in this retrospective study. METHODS: Smoking status and
      neutropenia along with other clinical parameters were recorded in 151 patients
      receiving first-line gemcitabine-based chemotherapy for advanced solid tumors.
      RESULTS: Tumor types included breast (9.3%), lung (4.6%), pancreatobiliary
      (70.9%), or other/unknown primary cancer (15.2%). Logistic regression showed that
      never smokers had increased neutropenia versus current smokers (odds ratio: 3.5;
      95% confidence interval, CI: 1.1-11.4). A 5-unit increase in pack-years reduced
      the odds of having higher neutropenia toxicity by 6.3% (95% CI 12 to 1%; p =
      0.036). CONCLUSION: Smokers had less neutropenia than nonsmokers, a finding that
      was more pronounced with increasing pack-years. This pharmacodynamic marker of
      gemcitabine-induced neutropenia may result in less efficacy of gemcitabine.
      Future prospective trials should correlate smoking, metabolizing phenotype,
      neutropenia, and response to gemcitabine therapy.

PMID- 24080958
TI  - Highly uniform and optical visualization of SERS substrate for pesticide analysis
      based on Au nanoparticles grafted on dendritic alpha-Fe2O3.
AB  - Here, Au nanoparticles (NPs) grafted on dendritic alpha-Fe2O3 (NPGDF) are
      designed as a highly uniform surface-enhanced Raman scattering (SERS) substrate
      with a feature of optical visualization by an optical microscope (OM) system and
      used for in situ detection of pesticide residues that are annually used in
      agriculture. With this strategy, the dendritic alpha-Fe2O3 has been synthesized
      by a hydrothermal method and significantly functionalized by an inductively
      coupled plasma (ICP) apparatus and then Au NPs were grafted on it densely and
      uniformly. In addition, the profile of NPGDF can be clearly observed using an OM
      platform of a Raman spectrometer, and the profile of SERS spectral mapping with
      NPGDF as substrate almost exactly coincides with the OM image, the electron
      microscope (EM) image and the elemental mapping of NPGDF, which indicates
      remarkable uniformity of the NPGDF as SERS substrate, thus ensuring the laser
      beam focuses on the efficient sites of the substrate under the OM platform.
      Moreover, NPGDF can be dispersed in the liquor and the NPGDF microparticles can
      be adsorbed on the target surface. Therefore, it can be used for in situ
      detection of pesticide residues on tea leaves, fruits etc., with high sensitivity
      and reproducibility. 

PMID- 24080960
TI  - Panax notoginseng saponins promote endothelial progenitor cell mobilization and
      attenuate atherosclerotic lesions in apolipoprotein E knockout mice.
AB  - BACKGROUND: Endothelial progenitor cells (EPCs) derived from the bone marrow (BM)
      play a key role in the homeostasis of vascular repair by enhanced
      reendothelialization. Panax notoginseng saponins (PNS), a highly valued
      traditional Chinese medicine, has been shown to reduce morbidity and mortality
      from coronary artery disease. The present research was designed to explore the
      contribution of progenitor cells to the progression of atherosclerotic plaques
      and the possible modulatory role of PNS in this process. METHODS: PNS (60 or 120
      mg/kg via intraperitoneal injection) was administered over 8 weeks in
      apolipoprotein E knockout mice on an atherogenic diet. The sizes and
      histochemical alteration of atherosclerotic lesions and numbers of EPCs in BM and
      peripheral blood were analyzed. The expression of chemokine stromal cell-derived
      factor 1alpha (SDF-1alpha) and its receptor, CXCR4, was monitored as well.
      RESULTS: PNS significantly reduced the lesion area and intima-to-media ratio
      compared to vehicle treatment. PNS also augmented endothelialization and reduced
      the smooth muscle cell (SMCs) content of the lesions. The number of c-kit and sca
      1 double-positive progenitor cells and flk-1 and sca-1 double-positive progenitor
      cells were significantly increased in the BM and the peripheral blood of the PNS
      treated groups. PNS treatment increased the plasma levels of SDF-1alpha and SCF
      as well as the BM levels of matrix metalloproteinase-9 (MMP-9). Moreover, the
      mRNA levels of SDF-1alpha and protein levels of CXCR4 were both increased in the
      BM of mice treated with PNS, while SDF-1alpha expression decreased. CONCLUSION:
      PNS reduce the size of atherosclerotic plaques, and this effect appears to
      involve progenitor cell mobilization. SDF-1alpha-CXCR4 interactions and the
      possible modulatory role of PNS in this process may contribute to the increased
      progenitor cell mobilization.

PMID- 24080961
TI  - Trends and factors associated with infant bed sharing, 1993-2010: the National
      Infant Sleep Position Study.
AB  - IMPORTANCE: A strong association between infant bed sharing and sudden infant
      death syndrome or unintentional sleep-related death in infants has been
      established. Occurrences of unintentional sleep-related deaths among infants
      appear to be increasing. OBJECTIVES: To determine the trends and factors
      associated with infant bed sharing from 1993 through 2010, including the
      association of physician advice on bed sharing. DESIGN: National Infant Sleep
      Position study conducted with annual telephone surveys. SETTING: The 48
      contiguous states. PARTICIPANTS: Nighttime caregivers of infants born within 7
      months of each survey administration. Approximately 1000 interviews were
      completed annually. MAIN OUTCOMES AND MEASURES: Infant bed sharing as a usual
      practice. RESULTS: Of 18 986 participants, 11.2% reported an infant sharing a bed
      as a usual practice. Bed sharing increased from 1993 (6.5%) to 2010 (13.5%).
      Although bed sharing increased significantly among white respondents from 1993 to
      2000 (P < .001), the increase from 2001 to 2010 was not significant (P = .48).
      Black and Hispanic respondents reported an increase in bed sharing throughout the
      study period, with no difference between the earlier and later periods (P = .63
      and P = .77, respectively). After accounting for the study year, factors
      associated with increase in infant bed sharing as a usual practice included
      maternal educational level of less than high school compared with college or
      greater (adjusted odds ratio, 1.42 [95% CI, 1.12-1.79]); black (3.47 [2.97
      4.05]), Hispanic (1.33 [1.10-1.61]), and other (2.46 [2.03-2.97]) maternal race
      or ethnicity compared with white race; household income of less than $20,000
      (1.69 [1.44-1.99]) and $20,000 to $50,000 (1.29 [1.14-1.45]) compared with
      greater than $50,000; living in the West (1.61 [1.38-1.88]) or the South (1.47
      [1.30-1.66]) compared with the Midwest; infants younger than 8 weeks (1.45 [1.21
      1.73]) or ages 8 to 15 weeks (1.31 [1.17-1.45]) compared with 16 weeks or older;
      and being born prematurely compared with full-term (1.41 [1.22-1.62]). Almost 46%
      of the participants reported talking to a physician about bed sharing. Compared
      with those who did not receive advice from a physician, those who reported their
      physicians had a negative attitude were less likely to have the infant share a
      bed (adjusted odds ratio, 0.66 [95% CI, 0.53-0.82]), whereas a neutral attitude
      was associated with increased bed sharing (1.38 [1.05-1.80]). CONCLUSIONS AND
      RELEVANCE: Our finding of a continual increase in bed sharing throughout the
      study period among black and Hispanic infants suggests that the current American
      Academy of Pediatrics recommendation about bed sharing is not universally
      followed. The factors associated with infant bed sharing may be useful in
      evaluating the impact of a broad intervention to change behavior.

PMID- 24080970
TI  - Association of the IL-1B +3954 C/T polymorphism with the risk of gastric cancer
      in a population in Western China.
AB  - With an estimate of 380 000 new cases each year, gastric cancer (GC) is one of
      the most frequently occurring cancers in China. Genes encoding proinflammatory
      and anti-inflammatory cytokines are good candidates for the study of
      susceptibility to GC. We tested the hypothesis that the polymorphisms of
      interleukin 1B (IL-1B) and IL-1RN contribute toward host susceptibility to GC. In
      a matched case-control design, we enrolled 308 pairs of GC and control
      participants between October 2010 and August 2011. We sequenced IL-1B +3954 C/T,
      IL-1RN -9876 G/A, -9739 A/G, and IL-1RN -9091 A/C using MALDI-TOF MS and
      collected demographic data as well as lifestyle factors using a questionnaire. GC
      patients reported statistically significantly greater proportions with family
      history of cancer (29.9 vs. 10.7%, P<0.01) and alcohol drinking (54.5 vs. 43.2%,
      P<0.01) than the controls. The proportion of irregular eaters was statistically
      higher among the patients than among the controls (66.7 vs. 24.4%, P<0.01). The
      IL-1B +3954 CT or the TT variant genotype was statistically significantly
      associated with a risk of GC [adjusted odds ratio (OR), 2.94; 95% confidence
      interval (CI), 1.06-8.15], whereas variants of IL-1RN -9876 G/A, IL-1RN -9739
      A/G, and IL-1RN -9091 A/C were not associated (adjusted OR, 1.29, 95% CI, 0.77
      2.16; adjusted OR, 1.25, 95% CI, 0.75-2.07; adjusted OR, 1.09, 95% CI, 0.71-1.67,
      respectively). Haplotypes established from the three polymorphisms of IL-1RN were
      not associated with a risk of GC. The IL-1B +3954 C/T polymorphism is associated
      with a risk of GC in our study. Lifestyle and environmental factors such as
      drinking, eating irregularly, and family history of cancer increase the risk. 

PMID- 24080959
TI  - Unraveling the mechanisms responsible for the comorbidity between metabolic
      syndrome and mental health disorders.
AB  - The increased prevalence and high comorbidity of metabolic syndrome (MetS) and
      mental health disorders (MHDs) have prompted investigation into the potential
      contributing mechanisms. There is a bidirectional association between MetS and
      MHDs including schizophrenia, bipolar disorder, depression, anxiety, attention
      deficit/hyperactivity disorder, and autism spectrum disorders. Medication side
      effects and social repercussions are contributing environmental factors, but
      there are a number of shared underlying neurological and physiological mechanisms
      that explain the high comorbidity between these two disorders. Inflammation is a
      state shared by both disorders, and it contributes to disruptions of
      neuroregulatory systems (including the serotonergic, dopaminergic, and
      neuropeptide Y systems) as well as dysregulation of the hypothalamic-pituitary
      adrenal axis. MetS in pregnant women also exposes the developing fetal brain to
      inflammatory factors that predispose the offspring to MetS and psychopathologies.
      Due to the shared nature of these conditions, treatment should address aspects of
      both mental health and metabolic disorders. Additionally, interventions that can
      interrupt the transfer of increased risk of the disorders to the next generation
      need to be developed. (c) 2013 S. Karger AG, Basel. 

PMID- 24080962
TI  - Dynamic whole-body PET parametric imaging: I. Concept, acquisition protocol
      optimization and clinical application.
AB  - Static whole-body PET/CT, employing the standardized uptake value (SUV), is
      considered the standard clinical approach to diagnosis and treatment response
      monitoring for a wide range of oncologic malignancies. Alternative PET protocols
      involving dynamic acquisition of temporal images have been implemented in the
      research setting, allowing quantification of tracer dynamics, an important
      capability for tumor characterization and treatment response monitoring.
      Nonetheless, dynamic protocols have been confined to single-bed-coverage limiting
      the axial field-of-view to ~15-20 cm, and have not been translated to the routine
      clinical context of whole-body PET imaging for the inspection of disseminated
      disease. Here, we pursue a transition to dynamic whole-body PET parametric
      imaging, by presenting, within a unified framework, clinically feasible multi-bed
      dynamic PET acquisition protocols and parametric imaging methods. We investigate
      solutions to address the challenges of: (i) long acquisitions, (ii) small number
      of dynamic frames per bed, and (iii) non-invasive quantification of kinetics in
      the plasma. In the present study, a novel dynamic (4D) whole-body PET acquisition
      protocol of ~45 min total length is presented, composed of (i) an initial 6 min
      dynamic PET scan (24 frames) over the heart, followed by (ii) a sequence of multi
      pass multi-bed PET scans (six passes * seven bed positions, each scanned for 45
      s). Standard Patlak linear graphical analysis modeling was employed, coupled with
      image-derived plasma input function measurements. Ordinary least squares Patlak
      estimation was used as the baseline regression method to quantify the
      physiological parameters of tracer uptake rate Ki and total blood distribution
      volume V on an individual voxel basis. Extensive Monte Carlo simulation studies,
      using a wide set of published kinetic FDG parameters and GATE and XCAT platforms,
      were conducted to optimize the acquisition protocol from a range of ten different
      clinically acceptable sampling schedules examined. The framework was also applied
      to six FDG PET patient studies, demonstrating clinical feasibility. Both
      simulated and clinical results indicated enhanced contrast-to-noise ratios (CNRs)
      for Ki images in tumor regions with notable background FDG concentration, such as
      the liver, where SUV performed relatively poorly. Overall, the proposed framework
      enables enhanced quantification of physiological parameters across the whole
      body. In addition, the total acquisition length can be reduced from 45 to ~35 min
      and still achieve improved or equivalent CNR compared to SUV, provided the true
      Ki contrast is sufficiently high. In the follow-up companion paper, a set of
      advanced linear regression schemes is presented to particularly address the
      presence of noise, and attempt to achieve a better trade-off between the mean
      squared error and the CNR metrics, resulting in enhanced task-based imaging.

PMID- 24080971
TI  - Characteristics of genetics-related news content in Black weekly newspapers.
AB  - BACKGROUND/AIMS/OBJECTIVES: The media are an important source of health
      information, especially for those with less access to regular health care. Black
      news outlets such as Black newspapers are a source of health information for
      African Americans. This study characterized media coverage of genetics-related
      information in Black weekly newspapers and general audience newspapers from the
      same communities. METHODS: All health stories in a sample of 24 Black weekly
      newspapers and 12 general audience newspapers from January 2004 to December 2007
      were reviewed for genetics-related stories. These stories were further coded for
      both journalistic and public health variables. RESULTS: Of all health-related
      stories identified, only 2% (n = 357) were considered genetics related. Genetics
      related stories in Black newspapers - compared to those in general audience
      newspapers - were larger, more locally and racially relevant, and more likely to
      contain recommendations or action steps to improve health or reduce disease risks
      and to mention the importance of knowing one's family history. Stories in general
      audience newspapers were more likely to discuss causes of disease, mention
      genetic testing or therapy, and suggest a high/moderate degree of genetic
      determinism. CONCLUSIONS: Black newspapers are a viable communication channel to
      disseminate findings and implications of human genome research to African
      American audiences.

PMID- 24080972
TI  - Early-life iron deficiency anemia alters the development and long-term expression
      of parvalbumin and perineuronal nets in the rat hippocampus.
AB  - Early-life iron deficiency anemia (IDA) alters the expression of critical genes
      involved in neuronal dendritic structural plasticity of the hippocampus, thus
      contributing to delayed maturation of electrophysiology, and learning and memory
      behavior in rats. Structural maturity in multiple cortical regions is
      characterized by the appearance of parvalbumin-positive (PV(+)) GABAergic
      interneurons and perineuronal nets (PNNs). Appearance of PV(+) interneurons and
      PNNs can serve as cellular markers for the beginning and end of a critical
      developmental period, respectively. During this period, the system progresses
      from an immature yet highly plastic condition, to a more mature and efficient
      state that is however less flexible and may exhibit poorer potential for recovery
      from injury. To test if fetal-neonatal IDA alters parvalbumin (PV) mRNA
      expression, protein levels, and the number of PV(+) interneurons and PNNs in the
      male rat hippocampus, pregnant dams were given an iron-deficient (ID) diet (3 mg
      iron/kg chow) from gestational day 2 to postnatal day (P) 7 and then placed on an
      iron-sufficient (IS) diet (198 mg/kg) for the remainder of the experiment. On
      this regimen, formerly ID animals become fully iron-replete by P56. Minimal
      levels of PV (mRNA and protein), PV(+) interneurons, and PNNs were found in IS
      and ID P7 rats. By P15, and continuing through P30 and P65, ID rats had reduced
      PV mRNA expression and protein levels compared to IS controls. While there were
      no differences in the number of PV(+) neurons at either P30 or P65, the
      percentage of PV(+) cells surrounded by PNNs was slightly greater in ID rats as
      compared to IS controls. The lower levels of these acknowledged critical period
      biomarkers in the ID group are consistent with studies that demonstrate later
      maturation of the acutely ID hippocampus and lower plasticity in the adult
      formerly ID hippocampus. The findings provide additional potential cellular bases
      for previously described electrophysiologic and behavioral abnormalities found
      during and following early-life IDA.

PMID- 24080974
TI  - Hearing preservation with full insertion of the FLEXsoft electrode.
AB  - OBJECTIVES: Hearing preservation (HP) in the context of cochlear implantation
      (CI) is indicative of an atraumatic insertion, which could potentially offer a
      clinical advantage to performance, whether such preservation was intended for the
      application of electoacoustic stimulation (EAS). Our goal was to determine the
      degree of HP after the implantation of a full-length electrode array (MedEl
      FLEXsoft). STUDY DESIGN: Prospective, within-subject repeated measure design.
      METHODS: Adult patients with residual low-frequency hearing who received a 31.5
      mm FlexSoft electrode array were included. Implantation using soft surgery
      techniques occurred at a single tertiary referral center between 2008 and 2011.
      Preoperative and postoperative audiometric data were compared. RESULTS: In 36
      consecutive patients at 1 year postimplantation, 6 (21%) maintained complete HP
      (an increase of low-frequency pure-tone average (PTA) <=10 dB from the
      preoperative value), and 19 (65%) maintained partial HP (an increase in low
      frequency PTA <=40 dB from the preoperative values) throughout the follow-up
      period (average, 368 d). Higher preoperative hearing threshold levels (HTLs) at
      1,000 Hz were associated with HP. CONCLUSION: Low-frequency HP is possible in
      patients implanted with the full-length FlexSoft electrode. Longer follow-up is
      required to determine if results are maintained over time and if such
      preservation is in fact advantageous to clinical outcomes. LEVEL OF EVIDENCE: 4.

PMID- 24080973
TI  - Urine specimen detection of concurrent nonprescribed medicinal and illicit drug
      use in patients prescribed buprenorphine.
AB  - Patients being treated with buprenorphine usually have a history of opioid
      dependence and may be predisposed to misuse of drugs. Concurrent drug misuse
      increases the risk of life-threatening drug interactions. This retrospective data
      analysis observed which nonprescribed and illicit drugs were most commonly
      detected in the urine of patients from pain management clinics taking
      buprenorphine with or without a prescription. GC, LC/MS and LC-MS-MS were used to
      quantify 20,929 urine specimens. The most prevalent illicit drug used in both the
      groups (prescribed and nonprescribed buprenorphine) was marijuana, followed by
      cocaine. The most prevalent nonprescribed medications abused by both the groups
      were benzodiazepines, followed by oxycodone and hydrocodone. The overall
      prevalence of illicit and nonprescribed drug use was significantly higher in
      subjects who used buprenorphine without a prescription versus prescribed use. Of
      the concurrent use of marijuana and cocaine with buprenorphine, cocaine is most
      concerning since it decreases exposure to buprenorphine (lower area under the
      concentration-time curve and maximum concentration). The concurrent use of
      nonprescribed benzodiazepines with buprenorphine can cause excess sedation
      leading to respiratory depression and even death. These findings highlight the
      importance of educating patients about these potential toxicities. Furthermore,
      pain providers should consider expanding the spectrum of drugs that they monitor
      in patients under treatment. 

PMID- 24080975
TI  - Intravascular extension of a glomus jugulare.

PMID- 24080976
TI  - Angioplasty and stenting for intractable pulsatile tinnitus caused by dural
      venous sinus stenosis: a case series report.
AB  - OBJECTIVE: Pulsatile tinnitus caused by dural venous sinus (DVS) stenosis is a
      newly identified form of tinnitus. Its persistent nature can severely affect
      patients' sleep and quality of life, leading to depression in severe cases. The
      aim of this report is to investigate the efficacy and safety of angioplasty and
      stenting in treating this form of tinnitus. STUDY DESIGN: Retrospective review.
      SETTING: Chinese PLA General Hospital. METHODS: Clinical data of 46 cases of
      pulsatile tinnitus caused by DVS stenosis treated between December 2009 and
      October 2012 using angioplasty and stenting were reviewed. Diagnosis of DVS
      abnormality was confirmed in all cases using digital subtraction angiography
      (DSA). Among these cases, stenosis was located in the transverse-sigmoid sinuses
      junction area ipsilateral to tinnitus in 44 cases and on both sides in the
      remaining 2 cases. Stenosis was treated with angioplasty and stenting in all
      cases. RESULTS: Pulsatile tinnitus disappeared immediately after the procedure in
      all 46 cases. There was no procedure-related complication. During the 2 to 36
      months' follow-up, there was no recurrence. CONCLUSION: These results indicate
      that DVS stenosis is the cause of pulsatile tinnitus in these cases and that
      angioplasty and stenting are an effective and safe treatment for intractable
      pulsatile tinnitus caused by DVS stenosis.

PMID- 24080977
TI  - Evaluation of quantitative head impulse testing using search coils versus video
      oculography in older individuals.
AB  - OBJECTIVE: To evaluate the validity of 2D video-oculography (VOG) compared with
      scleral search coils for horizontal AVOR gain estimation in older individuals.
      STUDY DESIGN: Cross-sectional validation study. SETTING: Tertiary care academic
      medical center. PATIENTS: Six individuals age 70 and older. INTERVENTIONS:
      Simultaneous eye movement recording with scleral search coil (over right eye) and
      EyeSeeCam VOG camera (over left eye) during horizontal head impulses. MAIN
      OUTCOME MEASURES: Best estimate search coil and VOG horizontal AVOR gain,
      presence of compensatory saccades using both eye movement recording techniques.
      RESULTS: We observed a significant correlation between search coil and VOG best
      estimate horizontal AVOR gain (r = 0.86, p = 0.0002). We evaluated individual
      head impulses and found that the shapes of the head movement and eye movement
      traces from the coil and VOG systems were similar. Specific features of eye
      movements seen in older individuals, including overt and covert corrective
      saccades and anticompensatory eye movements, were captured by both the search
      coil and VOG systems. CONCLUSION: These data suggest that VOG is a reasonable
      proxy for search coil eye movement recording in older subjects to estimate VOR
      gain and the approximate timing of corrective eye movements. VOG offers
      advantages over the conventional search coil method; it is portable and easy to
      use, allowing for quantitative VOR estimation in diverse settings such as a
      routine office-based practice, at the bedside, and potentially in larger scale
      population analyses.

PMID- 24080978
TI  - Letter to the editor in response to Faber et al. Bone-anchored hearing implant
      loading at 3 weeks: stability and tolerability after 6 months.

PMID- 24080979
TI  - Analysis of speech perception outcomes among patients receiving cochlear implants
      with auditory neuropathy spectrum disorder.
AB  - OBJECTIVE: Cochlear implantation (CI) is currently the main device option for
      children with auditory neuropathy spectrum disorder (ANSD) who receive minimal
      benefit from conventional amplification. This study examines potential prognostic
      factors associated with post-CI speech performance in this population. STUDY
      DESIGN: Retrospective chart review. SETTING: Academic center. PATIENTS: ANSD
      patients without inner ear abnormalities implanted with unilateral or bilateral
      CI between 1998 and 2010. INTERVENTION: CI and speech perception testing. MAIN
      OUTCOME MEASURE: Post-CI speech perception testing at 50 dBHL. "Good" performers
      were defined as patients with greater than 70% speech perception and "poor"
      performers less than 70%. Medical comorbidity, educational information, and
      social history were gathered. RESULTS: Twenty-seven patients met inclusion
      criteria. Mean age at diagnosis, first CI, and second CI in good performers were
      2.5 +/- 3.4, 3.4 +/- 3.6, and 3.8 +/- 1.6 years, respectively, compared with 9.7
      +/- 7.8, 14.8 +/- 12.9, and 8.9 +/- 3.5 in poor performers. Mean speech
      perception after first and second implantation for good performers trended at 85%
      and 90%, respectively, compared with 36% and 73% in poor performers. Better pre
      CI PTA correlated with better post-CI speech perception. Patients with bilateral
      CI demonstrated better speech perception outcomes compared with unilateral CI
      use. Poor performers had later age of implantation, lower socioeconomic status,
      and lack of family support compared with good performers. CONCLUSION: ANSD
      patients who do not benefit from conventional amplification do well when
      implanted at a young age with proper access to education and habilitation
      training. Medical, social, and economic information may be helpful in predicting
      positive outcomes.

PMID- 24080980
TI  - Letter to the editor in response to Faber et al. Bone anchored hearing implant
      loading at 3 weeks: stability and tolerability after 6 months.

PMID- 24080981
TI  - Cost of placement and complications associated with osseointegrated bone
      conducting hearing prostheses: a retrospective analysis of medicare billing data.
AB  - OBJECTIVE: To report the cost of placement and complications related to
      osseointegrated bone-conducting hearing prostheses (OBHPs) in a Medicare
      population. MATERIALS AND METHODS: We performed a retrospective analysis of
      nationwide Medicare claims data for operative and nonoperative complications
      associated with the placement of percutaneous OBHPs between the first quarter of
      2007 and the second quarter of 2009 for which there were 6 subsequent quarters of
      follow-up. We used Medicare Standard Analytical Files (SAF), which contain a 5%
      random sample of Medicare fee-for-service beneficiaries, excluding those that
      also were enrolled in a managed-care organization. RESULTS: We identified 118
      patients who had OBHPs placed in the requisite period. Their complication billing
      data were analyzed for the six-quarters after initial placement. Seventy patients
      (59%) had no billing codes for complications or repeat procedures after receiving
      the implant, whereas 48 patients (41%) had such codes. The total adjusted mean
      cost with repeat/revision operations or complications was $7,812 per patient
      compared with $6,733 for those without these issues, an increase of $1,079 or
      16%. DISCUSSION: We estimate that complications associated with the implantation
      of percutaneous OBHPs led to $417,616 in additional costs in the entire Medicare
      fee-for-service population during the study period and that the total cost of
      placement of these devices together with the cost of their complications totaled
      $6,789,248. In conclusion, the Medicare SAF database suggests that complications
      associated with OBHP increased the overall cost of placement by 16%. Like all
      surgical procedures, these complications and their associated costs should be
      taken into account when considering treatment options for patients who experience
      hearing loss.

PMID- 24080982
TI  - Predegenerated great auricular nerve graft in facial nerve defects.
AB  - OBJECTIVE: To compare axonal regeneration in an animal model after the repair of
      facial nerve defects with pre-degenerated (PD) and non-PD (NPD) great auricular
      nerve grafts. MATERIALS AND METHODS: The buccal branch of the facial nerve was
      completely sectioned in 18 New Zealand rabbits, which were randomized to 3
      treatment groups: PD great auricular nerve graft repair (PD group), NPD great
      auricular nerve graft repair (NPD group), and immediate end-to-end repair
      (control group). Axonal regeneration was examined using optical microscopy to
      assess the following variables: total number of myelinated axons and regenerating
      sprouts (MARS) that crossed the distal anastomosis, numbers of intra and
      extrafascicular MARS, and area of myelinated axons. RESULTS: The total number of
      myelinated axons (p = 0.008) and intrafascicular axons (p = 0.02) that crossed
      the distal anastomosis significantly differed between the NPD and control group.
      No significant differences were observed between the PD and control group or
      between the PD and NPD groups. CONCLUSION: Nerve repair with PD grafts could be
      an alternative treatment in the management of injuries resulting in facial nerve
      gaps.

PMID- 24080984
TI  - Charged stacks of dithiin, diselenin, thianthrene and selenanthrene radical
      cations: long range multicenter bonds.
AB  - The bonding mechanism of charged stacks of thianthrene and selenanthrene radical
      cations is studied using quantum-chemical methods. The investigation of the
      nature of the electronic ground state and the electronic structure via gas-phase
      multireference calculations brings insight into the interactions of such dimers
      and trimers as found in molecular crystals. Since thianthrene and selenanthrene
      are the dibenzo-homologues of dithiin and diselenin, the latter are taken as
      model systems to study the influence of the ring systems. For all investigated
      systems, the singlet state is the ground state. Multicenter bonds are formed
      between the singular occupied orbitals of the radicals. All dimers are found to
      be metastable. The thianthrene trimers, which are experimentally found in
      molecular crystals are also stable in the gas phase, while the analogue
      selenanthrene trimers are not. 

PMID- 24080983
TI  - CD8(+) T cell-mediated cytotoxicity toward Schwann cells promotes diabetic
      peripheral neuropathy.
AB  - BACKGROUND: Damage to Schwann cells has been reported in the development of
      diabetic peripheral neuropathy (DPN), but how Schwann cells are damaged has not
      been elucidated. METHODS: The highly expressed proteins in the PBMC of DPN
      patients were identified through MALDI-TOF/TOF and SELDI protein chip technology.
      The expression levels of CXCR3 were detected by qPCR and flow cytometric
      analysis. Transwell migration assay was to investigate the migration of CD8(+) T
      cells. Western-blot analysis was to detect the levels of p38 MAP kinases pathway
      related proteins and TNF-alpha, FasL, and PDL1. RESULTS: Two highly expressed
      proteins, CXCR3 and p38, were identified. Under high glucose conditions, CXCR3
      was elevated in CD8(+) T cells via the activation of p38 MAP kinases. Moreover,
      CXCL9, CXCL10, and CXCL11 expression were induced in Schwann cells, leading to
      the recruitment and infiltration of CD8(+) T cells into DPN tissues. Further
      study demonstrated that Schwann cells promoted activation of CD8(+) T cells and
      induced expression of TNF-alpha, FasL, and PDL1 on CD8(+) T cells, in return,
      CD8(+) T cells induced obvious apoptosis of Schwann cells. CONCLUSION: Our study
      indicates that CD8(+) T cells mediate cytotoxicity toward Schwann cells and play
      an important role in the development of DPN.

PMID- 24080985
TI  - Adverse neonatal outcomes associated with early-term birth.
AB  - IMPORTANCE: Full-term neonates born between 37 and 41 weeks' gestational age have
      been considered a homogeneous, low-risk group. However, recent evidence from
      studies based on mode of delivery has pointed toward increased morbidity
      associated with early-term cesarean section births (37-38 weeks) compared with
      term neonates (39-41 weeks). OBJECTIVE: To compare the short-term morbidity of
      early-term vs term neonates in a county-based birth cohort using the primary
      objective of admission to a neonatal intensive care unit (NICU) or neonatology
      service. DESIGN, SETTING, AND PARTICIPANTS: Retrospective population-based 3-year
      birth cohort study (January 1, 2006-December 31, 2008) at all major birth
      hospitals in Erie County, New York. All full-term live births comprised the birth
      cohort; this information was obtained from the hospitals' perinatal databases,
      and data pertaining to NICU or neonatology service admissions were extracted from
      individual medical records. EXPOSURE: Gestational age of early term (37(0/7)
      38(6/7) weeks) vs term (39(0/7)-41(0/7) weeks). MAIN OUTCOMES AND MEASURES:
      Admission to the NICU or neonatology service. RESULTS: There were 33,488 live
      births during the 3-year period, of which 29,741 had a gestational age between 37
      and 41 weeks. Of all live births, 9031 (27.0%) were early term. Compared with
      term infants, early-term neonates had significantly higher risks for the
      following: hypoglycemia (4.9% vs 2.5%; adjusted odds ratio [OR], 1.92), NICU or
      neonatology service admission (8.8% vs 5.3%; adjusted OR, 1.64), need for
      respiratory support (2.0% vs 1.1%; adjusted OR, 1.93), requirement for
      intravenous fluids (7.5% vs 4.4%; adjusted OR, 1.68), treatment with intravenous
      antibiotics (2.6% vs 1.6%; adjusted OR, 1.62), and mechanical ventilation or
      intubation (0.6% vs 0.1%; adjusted OR, 4.57). Delivery by cesarean section was
      common among early-term births (38.4%) and increased the risk for NICU or
      neonatology service admission (12.2%) and morbidity (7.5%) compared with term
      births. Among vaginal deliveries, early-term neonates (6.8%) had a significantly
      higher rate of NICU or neonatology service admission compared with term neonates
      (4.4%). CONCLUSIONS AND RELEVANCE: Early-term births are associated with high
      neonatal morbidity and with NICU or neonatology service admission. Evaluation of
      local prevalence data will assist in implementation of specific preventive
      measures and plans, as well as prioritize limited health care resources.

PMID- 24080987
TI  - Au/3DOM Co3O4: highly active nanocatalysts for the oxidation of carbon monoxide
      and toluene.
AB  - Three-dimensionally ordered macroporous Co3O4 (3DOM Co3O4) and its supported gold
      (xAu/3DOM Co3O4, x = 1.1-8.4 wt%) nanocatalysts were prepared using the
      polymethyl methacrylate-templating and bubble-assisted polyvinyl alcohol
      protected reduction methods, respectively. The 3DOM Co3O4 and xAu/3DOM Co3O4
      samples exhibited a surface area of 22-27 m(2) g(-1). The Au nanoparticles with a
      size of 2.4-3.7 nm were uniformly deposited on the macropore walls of 3DOM Co3O4.
      There were good correlations of oxygen adspecies concentration and low
      temperature reducibility with catalytic activity of the sample for CO and toluene
      oxidation. Among 3DOM Co3O4 and xAu/3DOM Co3O4, the 6.5Au/3DOM Co3O4 sample
      performed the best, giving a T90% (the temperature required for achieving a
      conversion of 90%) of -35  degrees C at a space velocity of 20 000 mL g(-1) h(-1)
      for CO oxidation and 256  degrees C at a space velocity of 40 000 mL g(-1) h(-1)
      for toluene oxidation. The effect of water vapor was more significant in toluene
      oxidation than in CO oxidation. The apparent activation energies (26 and 74 kJ
      mol(-1)) over 6.5Au/3DOM Co3O4 were lower than those (34 and 113 kJ mol(-1)) over
      3DOM Co3O4 for CO and toluene oxidation, respectively. It is concluded that the
      higher oxygen adspecies concentration, better low-temperature reducibility, and
      strong interaction between Au and 3DOM Co3O4 were responsible for the excellent
      catalytic performance of 6.5Au/3DOM Co3O4. 

PMID- 24080986
TI  - Serum analysis by 1H nuclear magnetic resonance spectroscopy: a new tool for
      distinguishing neuromyelitis optica from multiple sclerosis.
AB  - BACKGROUND: Neuromyelitis optica (NMO) and multiple sclerosis (MS), two
      inflammatory demyelinating diseases, are characterized by different therapeutic
      strategies. Currently, the only biological diagnostic tool available to
      distinguish NMO from MS is the specific serum autoantibody that targets aquaporin
      4, but its sensitivity is low. OBJECTIVE: To assess the diagnostic accuracy of
      metabolomic biomarker profiles in these two neurological conditions, compared to
      control patients. METHODS: We acquired serum spectra (47 MS, 44 NMO and 42
      controls) using proton nuclear magnetic resonance ((1)H-NMR) spectroscopy. We
      used multivariate pattern recognition analysis to identify disease-specific
      metabolic profiles. RESULTS: The (1)H-NMR spectroscopic analysis evidenced two
      metabolites, originating probably from astrocytes, scyllo-inositol and acetate,
      as promising serum biomarkers of MS and NMO, respectively. In 87.8% of MS
      patients, scyllo-inositol increased 0.15 to 3-fold, compared to controls and in
      74.3% of NMO patients, acetate increased 0.4 to 7-fold, compared to controls.
      Using these two metabolites simultaneously, we can discriminate MS versus NMO
      patients (sensitivity, 94.3%; specificity, 90.2%). CONCLUSION: This study
      demonstrates the potential of (1)H-NMR spectroscopy of serum as a novel,
      promising analytical tool to discriminate populations of patients affected by NMO
      or MS.

PMID- 24080988
TI  - Intracerebral hemorrhage after thrombolytic therapy in acute ischemic stroke
      patients with renal dysfunction.
AB  - PURPOSE: One complication of thrombolysis is intracranial hemorrhage (ICH). We
      investigated whether treatment with tissue plasminogen activator (t-PA) for
      ischemic infarction results in a higher risk of ICH in patients with kidney
      dysfunction, who are predisposed to treatment complications due to their bleeding
      tendency. METHODS: A total of 297 patients given thrombolytic therapy for
      ischemic stroke were classified into 2 groups on the basis of their estimated
      renal glomerular filtration rate (eGFR). The outcome measures included the
      incidence of ICH and modified Rankin scale scores at 1 month and 1 year. RESULTS:
      ICH was more common in the renal dysfunction group (23 vs. 12.5%). Nevertheless,
      multivariate logistic regression showed that the odds of ICH were not high in the
      group with low eGFR. Also, eGFR values <60 ml/min/1.73 m(2) did not predict the
      odds for functional dependence or death at 1 month and 1 year. CONCLUSION: After
      adjusting for confounding factors, the odds ratio for ICH was not higher in
      intravenous t-PA-treated stroke patients with renal dysfunction. A trend to the
      occurrence of ICH among these patients, however, was noted. Renal dysfunction
      does not predict the odds for functional dependence or death at 1 month and 1
      year.

PMID- 24080989
TI  - Deterioration in renal function is associated with increased arterial stiffness.
AB  - BACKGROUND: Higher levels of baseline pulse wave velocity (PWV) have been
      associated with longitudinal decline in renal function in patients with kidney
      disease. We examined longitudinal decline in renal function in relation to levels
      of PWV. We hypothesized that longitudinal decline in renal function in a
      community-based, nonclinic sample would be associated with higher levels of PWV.
      METHODS: We conducted a 4-5 year longitudinal study with 482 community-living
      individuals free from acute stroke, dementia, and end-stage renal disease (mean
      age = 60.9 years; 59% women; 93.2% white; 10% with diabetes mellitus; mean
      estimated glomerular filtration rate (eGFR) = 79.2 ml/min/1.73 m2). Multiple
      linear regression analyses were used to examine the association between changes
      in renal function (eGFR and serum creatinine) from baseline to follow-up and PWV
      levels at follow-up, the outcome measure. Regression coefficients were adjusted
      for age, sex, education, race/ethnicity, weight, activity level, mean arterial
      pressure, treatment of hypertension, and cardiovascular risk factors. RESULTS:
      With adjustment for covariables, decline in renal function was associated with
      higher levels of PWV over a mean follow-up of 4.68 years. CONCLUSIONS: Decline in
      renal functioning from baseline levels measured 4-5 years before measurement of
      PWV is related to higher levels of PWV in a community sample.

PMID- 24080990
TI  - Visit-to-visit blood pressure variability, silent cerebral injury, and risk of
      stroke.
AB  - Apart from the well-known role of hypertension in cerebrovascular disease, visit
      to-visit blood pressure (BP) variability is emerging as an independent risk
      factor for stroke. Although the underlying mechanism is not fully understood,
      artery remodeling is thought to be closely involved in the relationship between
      visit-to-visit BP variability and stroke. This review article summarizes the
      recent literature on these topics. Silent cerebral injury is considered to serve
      as a common pathophysiology in the relationship of visit-to-visit BP variability
      with cognitive impairment and stroke. Here we review visit-to-visit BP
      variability, some comparisons of the effects of antihypertensive agents on visit
      to-visit BP variability, and an issue regarding the impact of these agents on
      stroke.

PMID- 24080991
TI  - Bortezomib administered subcutaneously is well tolerated in bortezomib-based
      combination regimens used in patients with multiple myeloma.
AB  - OBJECTIVE: Bortezomib (Btz) has emerged as a standard of care in the treatment of
      patients with multiple myeloma (MM), but Btz-induced peripheral neuropathy (PNP)
      has a particularly negative impact on patients' quality of life. According to a
      recent study, PNP was significantly less frequent with subcutaneous
      administration of Btz. Here, we report our experience regarding the efficacy and
      tolerability of standard combination regimens in MM with subcutaneous Btz.
      METHODS: 14 consecutive patients with newly diagnosed MM were included in this
      analysis. Btz was used in different combination regimens (Btz with dexamethasone
      with/without thalidomide or Btz combined with melphalan and prednisone). Standard
      criteria were applied to evaluate response and toxicity. RESULTS: Hematological
      toxicities occurred only at grades 1-2 and included anemia (71%) and
      thrombocytopenia (21%). Nonhematologic side effects at grades 1-2 were local skin
      reactions at the subcutaneous injection site, which were self-limited. No notable
      gastrointestinal toxicity was observed with subcutaneous Btz, and therefore
      routine use of intravenous hydration and antiemetics was abandoned. Overall
      response rate for transplant-eligible patients was 86%. CONCLUSIONS: Our results
      confirm the improved toxicity profile of the subcutaneous administration of Btz
      in various standard Btz-based combination regimens. In addition, patient
      management with subcutaneous administration has been markedly ameliorated at our
      center.

PMID- 24080992
TI  - RTOG 0518: randomized phase III trial to evaluate zoledronic acid for prevention
      of osteoporosis and associated fractures in prostate cancer patients.
AB  - BACKGROUND: RTOG 0518 evaluated the potential benefit of zoledronic acid therapy
      in preventing bone fractures for patients with high grade and/or locally
      advanced, non-metastatic prostate adenocarcinoma receiving luteinizing hormone
      releasing hormone (LHRH) agonist and radiotherapy (RT). METHODS: Eligible
      patients with T-scores of the hip (<-1.0, but >-2.5 vs >-1.0) and negative bone
      scans were prospectively randomized to either zoledronic acid, 4 mg, concurrently
      with the start of RT and then every six months for a total of 6 infusions (Arm 1)
      or observation (Arm 2). Vitamin D and calcium supplements were given to all
      patients. Secondary objectives included quality of life (QOL) and bone mineral
      density (BMD) changes over a period of three years. RESULTS: Of 109 patients
      accrued before early closure, 96 were eligible. Median follow-up was 36.3 months
      for Arm 1 and 34.8 months for Arm 2. Only two patients experienced a bone
      fracture (one in each arm) resulting in no difference in freedom from any bone
      fracture (P=0.95), nor in QOL. BMD percent changes from baseline to 36 months
      were statistically improved with the use of zoledronic acid compared to
      observation for the lumbar spine (6% vs -5%, P<0.0001), left total hip (1% vs 
      8%, P=0.0002), and left femoral neck (3% vs -8%, P=0.0007). CONCLUSIONS: For
      patients with advanced, non-metastatic prostate cancer receiving LHRH agonist and
      RT, the use of zoledronic acid was associated with statistically improved BMD
      percent changes. The small number of accrued patients resulted in decreased
      statistical power to detect any differences in the incidence of bone fractures or
      QOL.

PMID- 24080993
TI  - Exploratory analysis of the visceral disease subgroup in a phase III study of
      abiraterone acetate in metastatic castration-resistant prostate cancer.
AB  - BACKGROUND: Visceral disease, non-nodal soft-tissue metastases predominantly
      involving the lung and liver, is a negative prognostic factor in patients with
      metastatic castration-resistant prostate cancer (mCRPC). An exploratory analysis
      of COU-AA-301 assessed whether abiraterone acetate (AA) improved overall survival
      (OS) in mCRPC patients with visceral disease progressing post docetaxel. METHODS:
      In COU-AA-301, post-docetaxel mCRPC patients were randomized 2:1 to AA 1000 mg
      (n=797) or placebo (n=398) once daily, each with prednisone 5 mg b.i.d. The
      primary end point was OS; secondary end points included radiographic progression
      free survival (rPFS), PSA response rate and objective response rate (ORR).
      Treatment effects in visceral disease (n=352) and non-visceral disease (n=843)
      subsets were examined using final data (775 OS events). RESULTS: AA plus
      prednisone produced similar absolute improvement in median OS in patients with
      (4.6 months) and without (4.8 months) visceral disease versus prednisone; hazard
      ratios (HRs) were 0.79 (95% confidence interval (CI): 0.60-1.05; P=0.102) and
      0.69 (95% CI: 0.58-0.83; P<0.0001), respectively. Treatment with AA plus
      prednisone significantly and comparably improved secondary endpoint outcomes
      versus prednisone in both the subsets: the HRs for rPFS were 0.60 (95% CI: 0.46
      0.78; P=0.0002) and 0.68 (95% CI: 0.58-0.80; P<0.0001) in visceral and non
      visceral disease subsets, respectively. PSA response rates were 28% versus 7% in
      the visceral disease subsets and 30% versus 5% in the non-visceral disease
      subsets (both P<0.0001), and ORRs were 11% versus 0% (P=0.0058) and 19% versus 5%
      (P=0.0010), respectively. The incidence of grade 3/4 adverse events was similar
      between the subsets and between the treatment arms in each subset. Adverse events
      related to CYP17 blockade were increased in the AA arms and were similar in
      patients with or without visceral disease. CONCLUSIONS: AA plus prednisone
      provides significant clinical benefit, including improvements in OS and secondary
      end points, in post-docetaxel mCRPC patients with or without baseline visceral
      disease. The presence of visceral disease does not preclude clinical benefit from
      abiraterone.

PMID- 24080994
TI  - Dynamic whole-body PET parametric imaging: II. Task-oriented statistical
      estimation.
AB  - In the context of oncology, dynamic PET imaging coupled with standard graphical
      linear analysis has been previously employed to enable quantitative estimation of
      tracer kinetic parameters of physiological interest at the voxel level, thus,
      enabling quantitative PET parametric imaging. However, dynamic PET acquisition
      protocols have been confined to the limited axial field-of-view (~15-20 cm) of a
      single-bed position and have not been translated to the whole-body clinical
      imaging domain. On the contrary, standardized uptake value (SUV) PET imaging,
      considered as the routine approach in clinical oncology, commonly involves multi
      bed acquisitions, but is performed statically, thus not allowing for dynamic
      tracking of the tracer distribution. Here, we pursue a transition to dynamic
      whole-body PET parametric imaging, by presenting, within a unified framework,
      clinically feasible multi-bed dynamic PET acquisition protocols and parametric
      imaging methods. In a companion study, we presented a novel clinically feasible
      dynamic (4D) multi-bed PET acquisition protocol as well as the concept of whole
      body PET parametric imaging employing Patlak ordinary least squares (OLS)
      regression to estimate the quantitative parameters of tracer uptake rate Ki and
      total blood distribution volume V. In the present study, we propose an advanced
      hybrid linear regression framework, driven by Patlak kinetic voxel correlations,
      to achieve superior trade-off between contrast-to-noise ratio (CNR) and mean
      squared error (MSE) than provided by OLS for the final Ki parametric images,
      enabling task-based performance optimization. Overall, whether the observer's
      task is to detect a tumor or quantitatively assess treatment response, the
      proposed statistical estimation framework can be adapted to satisfy the specific
      task performance criteria, by adjusting the Patlak correlation-coefficient (WR)
      reference value. The multi-bed dynamic acquisition protocol, as optimized in the
      preceding companion study, was employed along with extensive Monte Carlo
      simulations and an initial clinical (18)F-deoxyglucose patient dataset to
      validate and demonstrate the potential of the proposed statistical estimation
      methods. Both simulated and clinical results suggest that hybrid regression in
      the context of whole-body Patlak Ki imaging considerably reduces MSE without
      compromising high CNR. Alternatively, for a given CNR, hybrid regression enables
      larger reductions than OLS in the number of dynamic frames per bed, allowing for
      even shorter acquisitions of ~30 min, thus further contributing to the clinical
      adoption of the proposed framework. Compared to the SUV approach, whole-body
      parametric imaging can provide better tumor quantification, and can act as a
      complement to SUV, for the task of tumor detection.

PMID- 24080995
TI  - High evolutionary dynamism in 5S rDNA of fish: state of the art.
AB  - The 5S ribosomal DNA (rDNA) consists of one transcriptional unit of about 120
      base pairs, which is separated from the next unit by a non-transcribed spacer
      (NTS). The coding sequence and the NTS together form a repeat unit which can be
      found in hundreds to thousands of copies tandemly repeated in the genomes. The
      NTS regions seem to be subject to rapid evolution. The first general model of
      evolution of these multigene families was referred to as divergent evolution,
      based on studies using hemoglobin and myoglobin as model systems. Later studies
      showed that nucleotide sequences of different multigene family members are more
      closely related within species than between species. This observation led to a
      new model of multigene family evolution, termed concerted evolution. Another
      model of evolution, named the birth-and-death model, has been found to be more
      suitable to explain the long-term evolution of these multigene families.
      According to this model, new genes originate by successive duplications, and
      these new genes are either maintained for a long time or are lost, or else
      degenerate into pseudogenes. In this review we describe different sources of
      variability in the 5S rDNA genes observed in several distinct fish species. This
      variability is mainly referred to NTSs and includes the presence of other
      multigene families (mainly LINEs, SINEs, non-LTR retrotransposons, and U snRNA
      families). Different types of microsatellites have also been found to contribute
      to the increase of variability in this region. Our recent results suggest that
      horizontal transfer contributes to the increase of diversity in the NTSs of some
      species. Variability in the 5S rDNA coding region affecting the stability of the
      structure, but without effects on the function of the 5S rRNA, is also described.
      Retrotransposons seem to be responsible for the high dynamism of 5S rDNA, while
      microsatellites acting as recombination hot spots could stabilize a wide variety
      of unusual DNA structures, affecting DNA replication and enhancing or decreasing
      promoter activity in gene expression. The relationship between the high
      variability found at molecular level and the low variability found at chromosomal
      level is also discussed.

PMID- 24080996
TI  - Novel high performance asymmetrical squaraines for small molecule organic solar
      cells with a high open circuit voltage of 1.12 V.
AB  - An asymmetrically substituted squaraine ASQC bearing a 9-carbazyl substituent
      exhibits an extremely deep HOMO energy level of -5.46 eV and a relatively low
      bandgap of 1.65 eV, hence renders solution-processed organic solar cells with an
      impressive Voc of up to 1.12 V and a PCE of 2.82%. 

PMID- 24080997
TI  - Identification of adult septic patients in the prehospital setting: a comparison
      of two screening tools and clinical judgment.
AB  - BACKGROUND: Timely identification and treatment of sepsis is crucial for patient
      outcome. The aim of this study was to compare two previously unvalidated
      prehospital sepsis screening tools with clinical judgment by emergency medical
      services (EMS) personnel with respect to identification of septic patients.
      PATIENTS AND METHODS: We carried out a retrospective cross-sectional study of 353
      adult patients, transported by the EMS, with a hospital discharge International
      Classification of Diseases code consistent with sepsis. We analyzed EMS records
      for the identification of sepsis according to two screening tools and clinical
      judgment by EMS providers. The Robson screening tool includes temperature, heart
      rate, respiratory rate, altered mental status, plasma glucose, and a history
      suggestive of a new infection. BAS 90-30-90 refers to the vital signs: oxygen
      saturation, respiratory rate, and systolic blood pressure. McNemar's two related
      samples test was used to compare the sensitivity of the two screening tools with
      the sensitivity of clinical judgment. RESULTS: The Robson screening tool had a
      sensitivity of 75% (18 out of 24 patients for whom all parameters were
      documented, P<0.001, as compared with clinical judgment). BAS 90-30-90 had a
      sensitivity of 43% (76 out of 175 patients, P<0.001). EMS personnel documented
      suspected sepsis in 42 out of 353 (12%) patients with sepsis. CONCLUSION: The
      Robson screening tool had a sensitivity superior to both BAS 90-30-90 and
      clinical judgment. This supports our hypothesis that the implementation of a
      screening tool could lead to increased prehospital identification of sepsis,
      which may enable a more timely treatment of these patients.

PMID- 24080998
TI  - Walkouts from the emergency department: characteristics, reasons and medical care
      needs.
AB  - OBJECTIVES: The aim of this study was to assess the walkout rate and to identify
      influencing patient and visit characteristics on walkout. Furthermore, we
      assessed the reasons for leaving and medical care needs after leaving. METHODS:
      In a 4-month population-based cohort study, the characteristics and influencing
      factors of walkout from two emergency departments in the Netherlands were
      studied. Afterwards, a follow-up telephone interview was conducted to assess the
      reasons for leaving and medical care needed. RESULTS: A total of 169 out of 23
      780 (0.7%) registered patients left without treatment, of whom 62% left after
      triage. Of the triaged walkouts, 26% had urgent or highly urgent medical
      complaints and target times to treatment had elapsed for 54% of the triaged
      walkouts. Independent predictors of leaving without treatment included being self
      referred, arriving during the evening or night or during crowded conditions, and
      relatively lower urgency triage allocation. Ninety (53%) walkouts were contacted
      afterwards by phone. Long waiting time (61%) was the most-cited prime reason for
      leaving. Medical problems had resolved spontaneously in 19 of the 90 (21%)
      walkouts, and 47 (52%) walkouts reported having sought medical care elsewhere.
      For 24 of the 90 (27%) walkouts with persisting complaints, medical care was
      advised during the follow-up telephone call. CONCLUSION: The average observed
      daily walkout rate was 1.4 patients over the 4-month period. In general, walkouts
      are self-referrals with lower urgent complaints, arriving during the evening or
      night shift or during crowded conditions. Most walkouts leave because of
      perceived long waiting times.

PMID- 24080999
TI  - Comparing the performance of different devices for endotracheal intubation in a
      simulated entrapped patient.

PMID- 24081000
TI  - Endobronchial ultrasound-guided transbronchial needle aspiration of an
      intravascular sarcoma metastasis.
AB  - The role of endobronchial ultrasound-guided transbronchial needle aspiration
      (EBUS-TBNA) in the diagnosis of endovascular lesions has rarely been described.
      We report a case of EBUS-TBNA of a solid mass in the left pulmonary artery in a
      patient with synovial sarcoma of the kidney, which was performed without
      complications and led to the diagnosis of metastatic disease. EBUS-TBNA seems to
      be a rapid, minimally invasive, safe and effective diagnostic procedure in
      selected cases of endovascular lesions. 

PMID- 24081001
TI  - A highly sensitive electrochemical aptasensor for thrombin detection using
      functionalized mesoporous silica@multiwalled carbon nanotubes as signal tags and
      DNAzyme signal amplification.
AB  - In this work, we demonstrated a novel sensitive sandwich-type pseudobienzyme
      aptasensor for thrombin detection. Greatly amplified sensitivity was based on
      mesoporous silica-multiwalled carbon nanotube (mSiO2@MWCNT) nanocomposites as
      enhanced materials and a pseudobienzyme electrocatalytic system. Firstly, the
      mSiO2@MWCNT nanocomposites not only have good biocompatibility and a suitable
      microenvironment for stabilizing the aptamer assembly, but also can load large
      amounts of electron mediator thionine (Thi), platinum nanoparticles (PtNPs) and
      hemin/G-quadruplex bioelectrocatalytic complex. Moreover, in the presence of H2O2
      in an electrolytic cell, the synergistic reaction of PtNPs and hemin/G-quadruplex
      bioelectrocatalyzed the reduction of H2O2, dramatically amplifying the response
      signals of electron mediator Thi and improving the sensitivity. Secondly,
      dendrimer functionalized reduced graphene oxide (PAMAM-rGO) as the biosensor
      platform enhanced the surface area for the immobilization of abundant primary
      aptamers as well as facilitated electron transfer from Thi to the electrode, thus
      amplifying the detection response. Using the above multiple effects, the approach
      showed a high sensitivity and a wider linearity for the detection of thrombin in
      the range between 0.0001 nM and 80 nM with a detection limit of 50 fM. This new
      design avoided the fussy labeling process and the spatial distribution of each
      sequentially acting enzyme, which provided an ideal candidate for the development
      of a sensitive and simple bioanalytical platform. 

PMID- 24081002
TI  - The Centers for Medicare & Medicaid Services and amyloid-beta positron emission
      tomography for Alzheimer disease.

PMID- 24081009
TI  - Sleep to forget: interference of fear memories during sleep.
AB  - Memories are consolidated and strengthened during sleep. Here we show that
      memories can also be weakened during sleep. We used a fear-conditioning paradigm
      in mice to condition footshock to an odor (conditioned stimulus (CS)). Twenty
      four hours later, presentation of the CS odor during sleep resulted in an
      enhanced fear response when tested during subsequent wake. However, if the re
      exposure of the CS odor during sleep was preceded by bilateral microinjections of
      a protein synthesis inhibitor into the basolateral amygdala, the subsequent fear
      response was attenuated. These findings demonstrate that specific fear memories
      can be selectively reactivated and either strengthened or attenuated during
      sleep, suggesting the potential for developing sleep therapies for emotional
      disorders. 

PMID- 24081010
TI  - Crystallization under nanoscale confinement.
AB  - Classical crystal growth models posit that crystallization outcomes are
      determined by nuclei that resemble mature crystal phases, but at a critical size
      where the volume free energy of nuclei begins to offset the unfavorable surface
      free energy arising from the interface with the growth medium. Crystallization
      under nanoscale confinement offers an opportunity to examine nucleation and phase
      transformations at length scales corresponding to the critical size, at which
      kinetics and thermodynamics of nucleation and growth intersect and dramatic
      departures in stability compared to bulk crystals can appear. This tutorial
      review focuses on recent investigations of the crystallization of organic
      compounds in nanoporous matrices that effectively provide millions of nanoscale
      reactors in a single sample, ranging from controlled porous glass (CPG) beads to
      nanoporous block-copolymer monoliths to anodic aluminum oxide (AAO) membranes.
      Confinement of crystal growth in this manner provides a snapshot of the earliest
      stages of crystal growth, with insights into nucleation, size-dependent
      polymorphism, and thermotropic behavior of nanoscale crystals. Moreover, these
      matrices can be used to screen for crystal polymorphs and assess their stability
      as nanocrystals. The well-aligned cylindrical nanoscale pores of polymer
      monoliths or AAO also allow determination of preferred orientation of embedded
      nanocrystals, affording insight into the competitive nature of nucleation,
      critical sizes, and phase transition mechanisms. Collectively, these
      investigations have increased our understanding of crystallization at length
      scales that are deterministic while suggesting strategies for controlling
      crystallization outcomes. 

PMID- 24081011
TI  - Concurrent validity of the TIMP and the Bayley III scales at 6 weeks corrected
      age.
AB  - PURPOSE: Examine agreement between the Test of Infant Motor Performance (TIMP)
      and the Bayley III. METHODS: One hundred forty-five infants born at 29 to 34
      weeks gestation with socioenvironmental risk factors were tested on the TIMP and
      Bayley III at 6 weeks corrected age (CA). Scores were correlated to assess
      convergence/divergence of content. Decision analysis using a cutoff of the mean
      on the Bayley Motor Composite and -0.5 and -1 SD from the mean on the TIMP
      assessed agreement on delay/nondelay. RESULTS: The TIMP-Bayley Motor Composite
      correlation was 0.546, with Cognitive was 0.310, and with Language was 0.281.
      Nine percent of infants scored less than -1.0 SD on the TIMP, while no child
      scored less than -1 SD on the Bayley Motor scale (sensitivity, 31%). CONCLUSIONS:
      Convergent validity between the TIMP and the Bayley Motor scale was demonstrated,
      but no infant showed delay on any Bayley scale. The TIMP is preferred for early
      assessment of infants.

PMID- 24081013
TI  - New guidelines for the disclosure of academic-industry financial ties and
      modeling professionalism during medical education.

PMID- 24081012
TI  - Commentary on "Concurrent validity of the TIMP and the Bayley III scales at 6
      weeks corrected age".

PMID- 24081014
TI  - Inhibition of colonic tumor growth by the selective SGK inhibitor EMD638683.
AB  - BACKGROUND: The serum and glucocorticoid inducible kinase SGK1, which was
      originally cloned from mammary tumor cells, is highly expressed in some but not
      all tumors. SGK1 confers survival to several tumor cells. Along those lines, the
      number of colonic tumors following chemical carcinogenesis was decreased in SGK1
      knockout mice. Recently, a highly selective SGK inhibitor (EMD638683) has been
      developed. The present study explored whether EMD638683 affects survival of colon
      carcinoma cells in vitro and impacts on development of colonic tumors in vivo.
      METHODS: Colon carcinoma (Caco-2) cells were exposed to EMD638683 with or without
      exposure to radiation (3 Gray) and cell volume was estimated from forward
      scatter, phosphatidylserine exposure from annexin V binding, mitochondrial
      potential from JC-9 fluorescence, caspase 3 activity from CaspGlow Fluorescein
      staining, DNA degradation from propidium iodide staining as well as late
      apoptosis from annexin-V FITC and propidium iodide double staining. In vivo tumor
      growth was determined in wild type mice subjected to chemical carcinogenesis
      (intraperitoneal injection of 20 mg/kg 1,2-dimethylhydrazine followed by three
      cycles of 30 g/L synthetic dextran sulfate sodium in drinking water for 7 days).
      RESULTS: EMD638683 treatment significantly augmented the radiation-induced
      decrease of forward scatter, increase of phosphatidylserine exposure, decrease of
      mitochondrial potential, increase of caspase 3 activity, increase of DNA
      fragmentation and increase of late apoptosis. The in vivo development of tumors
      following chemical carcinogenesis was significantly blunted by treatment with
      EMD638683. CONCLUSIONS: EMD638683 promotes radiation-induced suicidal death of
      colon tumor cells in vitro and decreases the number of colonic tumors following
      chemical carcinogenesis in vivo.

PMID- 24081015
TI  - Semiconductor hierarchically structured flower-like clusters for dye-sensitized
      solar cells with nearly 100% charge collection efficiency.
AB  - By combining the ease of producing ZnO nanoflowers with the advantageous chemical
      stability of TiO2, hierarchically structured hollow TiO2 flower-like clusters
      were yielded via chemical bath deposition (CBD) of ZnO nanoflowers, followed by
      their conversion into TiO2 flower-like clusters in the presence of TiO2
      precursors. The effects of ZnO precursor concentration, precursor amount, and
      reaction time on the formation of ZnO nanoflowers were systematically explored.
      Dye-sensitized solar cells fabricated by utilizing these hierarchically
      structured ZnO and TiO2 flower clusters exhibited a power conversion efficiency
      of 1.16% and 2.73%, respectively, under 100 mW cm(-2) illumination. The intensity
      modulated photocurrent/photovoltage spectroscopy (IMPS/IMVS) studies suggested
      that flower-like structures had a fast electron transit time and their charge
      collection efficiency was nearly 100%. 

PMID- 24081016
TI  - Material-specific transfer function model and SNR in CT.
AB  - This study presents an analytical model for the edge spread function (ESF) of a
      clinical CT system that allows reliable fits of noisy ESF data. The model was
      used for the calculation of the material-specific transfer function TF and an
      estimation of the signal transfer and the signal-to-noise ratio (SNR) in 2D.
      Images of the Catphan phantom were acquired with a clinical Siemens Somatom
      Sensation Cardiac 64 CT scanner combining four different x-ray tube outputs (40,
      150, 250 and 350 mAs) with four different reconstruction filters, which covered
      the range from very smooth (B10s) to very sharp (B70s). The images of the high-
      and mid-contrast cylinders of the phantom's 'Geometry and Sensitometry' module
      (air, Teflon, Delrin and PMP) were used to sample material-specific ESF curves.
      The ESF curves were fitted with the analytical model we developed based on a
      linear combination of Boltzmann and Gaussian functions. The analytical model of
      the ESF was used to obtain the Fourier-based material-specific transfer function
      TF, as well as the spatial-domain point spread function (PSF). TF was
      subsequently used to estimate the signal transfer, which was compared to the
      actual reconstructed image of a 3.0 mm diameter Teflon pin. The noise power
      spectrum (NPS) was calculated from images of a uniform water phantom under the
      same technique parameters. The task-specific SNR was calculated for all technique
      parameters from the model-based TF, the measured NPS and simulated 3 mm diameter
      disc signals modeling the aforementioned materials. Bootstrapping was performed
      to estimate the standard deviation of the TF and the SNR. The analytical model we
      developed accurately captured the features of the CT ESF data. The coefficient of
      determination R(2), a metric that describes the goodness of the fit, had a median
      value of 0.9995, and decreased for low tube output, low contrast and the sharp
      reconstruction filter. Our analysis showed that ESF, PSF and TF depended not only
      on the reconstruction filter, but also on the tube output and the material of the
      cylinders. For B40s and B70s, the TF of Delrin was significantly higher than the
      TF of other materials in the frequency range of 0.4-0.9 mm(-1). The estimated
      signal transfer agreed well with the actual reconstructed image of the Teflon
      pin. For the technique parameters we used the SNR values ranged between [64,
      320], [64, 281], [37, 137] and [33, 117] for air, Teflon, Delrin and PMP
      respectively. While for high-contrast materials the smoothest reconstruction
      filter resulted in the highest SNR, for mid-contrast materials the standard
      filter gave the best results. The presented approach provides an accurate,
      analytical description of the material-specific ESF, PSF and TF as well as an
      estimate of the signal transfer. The transfer function TF together with the NPS
      and simulated signals allow the calculation of a task-specific SNR. 

PMID- 24081017
TI  - Satisfaction after the Malone antegrade continence enema procedure in patients
      with spina bifida.
AB  - STUDY DESIGN: Retrospective chart review. OBJECTIVE: To evaluate the clinical
      outcomes and factors influencing patient satisfaction with Malone antegrade
      continence enema (MACE) in patients with spina bifida. SETTING: Japan. METHODS:
      We performed retrospective analysis of 21 patients with spina bifida who
      underwent surgical creation of an MACE stoma. Clinical outcomes were evaluated by
      medical records, operative notes and mailed questionnaires. Patient satisfaction
      scores (SSs) were measured on a modified visual analog scale (VAS) from 1 to 10,
      and the factors influencing the SS were analyzed. RESULTS: A 100% return rate for
      the mailed questionnaires was achieved. All patients underwent in situ
      appendicocecostomy with cecal plication. There was only one complication that
      required surgical revision. Regarding fecal continence, the overall success rate
      was 90%. Although 4 patients (19%) had severe irrigation pain and 4 patients
      (19%) found the washout time intolerably long, 18 (85%) of them were satisfied
      with the MACE procedure. Age at operation, experience of retrograde colonic enema
      (RCE), experience of stomal leakage, increased comfort at school or workplace and
      increased comfort at sleepovers significantly influenced SSs. CONCLUSION: MACE is
      a valuable option in achieving fecal continence in patients with spina bifida,
      with most patients being satisfied with the procedure. In our analysis, younger
      age at operation, previous experience of RCE, no stomal leakage and improvement
      of quality of life (enhanced comfort at school, workplace and sleepovers)
      significantly influenced the high satisfaction after MACE.

PMID- 24081018
TI  - Socioeconomic outcomes following spinal cord injury and the role of no-fault
      compensation: longitudinal study.
AB  - STUDY DESIGN: Longitudinal cohort study. OBJECTIVES: To estimate socioeconomic
      and work outcomes over 2 and a half years following spinal cord injury (SCI), and
      to compare those in receipt of compensation (Accident Compensation Corporation,
      ACC) and those not. SETTING: People admitted to the two spinal units in 2007-2009
      in New Zealand, where there is a unique no-fault compensation scheme for injury.
      METHODS: Interviews were conducted at ~6, 18 and 30 months after SCI and data
      collected on pre-SCI and post-SCI health and socioeconomic characteristics.
      Poisson regression, quantile regression and a linear mixed model regression were
      used to compare differences in outcomes. RESULTS: Of the 162 eligible people, 118
      (73%) participated and 91(77%) were followed to 30 months; 79% received ACC.
      Median personal income, self-reported standard of living and household income
      adequacy all fell slightly to 18 months and then stabilized at 30 months. At that
      time, 49% had returned to paid work. Among those not eligible for ACC, income
      fell to less than half the ACC group (P<0.006 after adjustment), and return to
      work was lower (29% versus 54%). CONCLUSION: The findings that most people
      retained their economic status and that return to work was relatively high appear
      to be due to the proportion entitled to the ACC no-fault compensation scheme for
      injury; with earnings-related compensation, a focus on rehabilitation to work and
      non-means-tested support services. This situation should mitigate against the
      downward spiral into poverty and further ill-health.

PMID- 24081020
TI  - Chromosomal mapping of repetitive DNA and cytochrome C oxidase I sequence
      analysis reveal differentiation among sympatric samples of Astyanax fasciatus
      (Characiformes, Characidae).
AB  - The genus Astyanax is a specious Neotropical fish group, occurring from the south
      area of the United States to Argentina. During the past few years, intensive
      studies on representatives of this group have been performed, broadening the
      genetic, taxonomic and biogeographical knowledge considerably. However,
      phylogenetic relationships among many species remain uncertain. Significant
      karyotypic variations occur in A. bimaculatus, A. scabripinnis and A. fasciatus,
      suggesting the existence of species complexes. Samples with different diploid
      numbers may be found in A. fasciatus and, in some cases, morphological
      differentiation among them is not easily verified due to the absence of clear
      diagnostic characteristics. In the present study, the organization of the A.
      fasciatus genome from the Tiete River, Mogi das Cruzes, SP, Brazil, was analyzed,
      describing the karyotype structure and the chromosomal mapping of 18S and 5S
      ribosomal DNA (rDNA), H1 and H3 histones genes, telomeric DNA, and Rex3
      transposable element. Sequencing of the cytochrome c oxidase I (COI) gene was
      also performed. Chromosomal analyses highlighted the occurrence of 2 distinct
      karyomorphs in the referred population, one with 2n = 46 and the other with 2n =
      48 chromosomes. Furthermore, physical mapping of the repetitive sequences and
      nucleotide analysis of the COI gene reinforce the genomic differentiation between
      those karyomorphs and corroborate the existence of 2 different lineages
      morphologically similar to A. fasciatus living in sympatry.

PMID- 24081019
TI  - Content and functional specifications for a standards-based multidisciplinary
      rounding tool to maintain continuity across acute and critical care.
AB  - BACKGROUND: Maintaining continuity of care (CoC) in the inpatient setting is
      dependent on aligning goals and tasks with the plan of care (POC) during
      multidisciplinary rounds (MDRs). A number of locally developed rounding tools
      exist, yet there is a lack of standard content and functional specifications for
      electronic tools to support MDRs within and across settings. OBJECTIVE: To
      identify content and functional requirements for an MDR tool to support CoC.
      MATERIALS AND METHODS: We collected discrete clinical data elements (CDEs)
      discussed during rounds for 128 acute and critical care patients. To capture
      CDEs, we developed and validated an iPad-based observational tool based on
      informatics CoC standards. We observed 19 days of rounds and conducted eight
      group and individual interviews. Descriptive and bivariate statistics and network
      visualization were conducted to understand associations between CDEs discussed
      during rounds with a particular focus on the POC. Qualitative data were
      thematically analyzed. All analyses were triangulated. RESULTS: We identified the
      need for universal and configurable MDR tool views across settings and users and
      the provision of messaging capability. Eleven empirically derived universal CDEs
      were identified, including four POC CDEs: problems, plan, goals, and short-term
      concerns. Configurable POC CDEs were: rationale, tasks/'to dos', pending results
      and procedures, discharge planning, patient preferences, need for urgent review,
      prognosis, and advice/guidance. DISCUSSION: Some requirements differed between
      settings; yet, there was overlap between POC CDEs. CONCLUSIONS: We recommend an
      initial list of 11 universal CDEs for continuity in MDRs across settings and 27
      CDEs that can be configured to meet setting-specific needs.

PMID- 24081021
TI  - Five hemoglobin variants in a double heterozygote for alpha- and beta-globin
      chain defects.
AB  - Genetic interactions of different defective globin chains could render laboratory
      diagnostics in a routine setting difficult. We report a hitherto undescribed
      condition of double heterozygosity for hemoglobin (Hb) Q-Thailand with alpha(+)
      thalassemia and Hb Tak found in 2 adult Thai individuals. Both patients were
      healthy and had no pertinent past medical history. A complete blood count
      revealed slight elevations of Hb and HCT values with low MCV and MCH.
      Interestingly, Hb analysis demonstrated, in addition to Hb A, A2, and F, as many
      as 5 Hb variants including Hb Tak (alpha(A)2beta(Tak)2), Q-Thailand
      (alpha(QT)2beta(A)2), QA2 (alpha(QT)2delta2), QF (alpha(QT)2gamma2), and a novel
      variant, Hb QTak (alpha(QT)2beta(Tak)2). Hematological findings of these unusual
      cases were compared with those of pure heterozygotes for Hb Q-Thailand and Hb Tak
      found in our series. Hb analysis using combined HPLC and capillary
      electrophoresis did help in the initial recognition and in making presumptive
      diagnoses, but definite diagnoses of these cases with complex alpha- and beta
      hemoglobinopathies could only be obtained after DNA analysis. 

PMID- 24081022
TI  - Amyloid-beta positron emission tomography in the diagnostic evaluation of
      alzheimer disease: summary of primary findings and conclusions.

PMID- 24081023
TI  - Comparison of alendronate and raloxifene for the management of primary
      hyperparathyroidism.
AB  - AIM: To evaluate and compare the efficacy of alendronate sodium (ALN) and
      raloxifene (RLX) for the management of primary hyperparathyroidism (PHPT) in
      postmenopausal female patients (pts) with osteoporosis. METHODS: Twenty-four
      postmenopausal women with osteoporosis who were diagnosed with PHPT, but refused
      the option of surgery, were enrolled. Participants were sequentially randomized
      into two groups: an ALN-group of 12 pts (70 mg/week) and a RLX-group of 12 pts
      (60 mg/day). The control group consisted of 10 pts with PHPT who did not have any
      indications for surgery. RESULTS: The decrease in ionized calcium levels was
      significantly more pronounced in the ALN group compared to the RLX and control
      groups (p<0.001). In terms of difference from baseline in bone mineral density
      (BMD) of the lumbar area in percentages over a period of 12 months, pts in the
      ALN and RLX groups both showed statistically significant improvements compared to
      pts in the control group (control vs ALN, p<0.001; control vs RLX, p<0.001). BMD
      measurements of the femoral and radial areas were comparable in all three groups.
      CONCLUSIONS: ALN and RLX may improve bone density in the lumbar area of
      osteoporotic post-menopausal women with PHPT. The more significant decrease in
      serum calcium levels which was observed in the ALN group compared to both RLX and
      control groups, suggests that ALN could be used for the short-term control of
      calcium levels in patients awaiting surgery.

PMID- 24081024
TI  - Assessment of adjuvant trastuzumab-associated cardiac toxicity in korean patients
      with breast cancer: a single-center analysis.
AB  - BACKGROUND: We performed this analysis to investigate the clinical presentation
      of trastuzumab-associated cardiac toxicity in Korean women. METHOD: 124 patients
      treated in a single institute from January 2006 to November 2011 with adjuvant
      trastuzumab therapy following primary surgery were identified from a database. We
      evaluated the cumulative incidence of cardiac toxicity, associated risk factors,
      and changes in cardiac function during trastuzumab treatment. RESULTS: The median
      age of patients was 50 years (range 27-73). After 12 months of follow-up, the
      cumulative incidence of cardiac toxicity was 12.1% (grade I: 8.1%, grade II:
      0.8%, grade III: 3.2%). In total, 4% of patients discontinued treatment due to
      cardiac dysfunction. The left ventricular ejection fraction (LVEF) recovered in
      all patients who discontinued or delayed treatment due to cardiac dysfunction
      following treatment discontinuation. The degree of the decrease in LVEF was large
      at 6 months after the initiation of treatment. A lower LVEF at baseline (<65%)
      was associated with cardiac toxicity. CONCLUSIONS: The low incidence of cardiac
      toxicity and the reversibility of cardiac dysfunction may validate the safety of
      trastuzumab treatment in Korean women with an acceptable baseline LVEF.

PMID- 24081025
TI  - The Aryl Hydrocarbon Receptor Nuclear Translocator (ARNT/HIF-1beta) is influenced
      by hypoxia and hypoxia-mimetics.
AB  - BACKGROUND: The Aryl Hydrocarbon Receptor Nuclear Translocator (ARNT, HIF-1beta)
      is a member of the basic-Helix-Loop-Helix PER/ARNT/SIM (bHLH/PAS) protein family
      and a vital transcriptional regulator regarding development and physiological
      adaptation processes. ARNT is discussed to be linked with cancer, and other
      diseases. ARNT is known to be translocated into the cell nucleus, where
      accumulation of the protein takes place. ARNT is a heterodimerisation partner of
      the xenobiotic ligand activated Aryl Hydrocarbon Receptor (AhR), the Single
      Minded proteins (SIM), the cardiovascular helix-loop-helix factor 1 and the
      Hypoxia Inducible Factor proteins (HIF-alpha). ARNT is obligatory for HIF-1, HIF
      2 and HIF-3 binding to DNA. Whereas degradation of the HIF-alpha subunits is
      suppressed by hypoxia, ARNT is generally regarded as constitutively expressed in
      excess within the cell, and stabilisation is commonly thought to be oxygen
      independent. However, we provide evidence that the regulation of ARNT is far more
      complex. The aim of our study was to reevaluate the regulation of ARNT
      expression. METHODS: We examined cell lines of different origin like MCF-7 and
      T47D (human breast cancer), HeLa (human cervix carcinoma), Hep3B and HepG2 (human
      hepatoma), Kelly (human neuroblastoma), REPC (human kidney) and Cos7 (primary
      primate kidney) cells. We used immunoblot analysis, densitometry, RT-PCR and
      transient transfection. RESULTS AND CONCLUSION: Our results show that ARNT
      protein levels are influenced by hypoxia and hypoxia mimetics such as cobalt(II)
      chloride (CoCl2) and dimethyloxalylglycine (DMOG) in a cell line specific manner.
      We demonstrate that this effect might be triggered by HIF-1alpha which plays an
      important role in the process of stabilizing ARNT in hypoxia.

PMID- 24081027
TI  - Molecularly designed architectures--the metalloligand way.
AB  - Designed materials offer noteworthy applications which are often architecture
      dependent. Despite knowing such a fact, one of the major challenges faced by the
      scientific community is to find ways to predict and, if possible, control the
      resultant architecture of a network. If such an exercise is fruitful, it creates
      enormous opportunities to synthesize exotic materials with tailor-made
      applications. Any network is composed of individual molecules and the transition
      from a single molecule to a network can be achieved through several routes taking
      advantage of synthetic chemistry. There exists a molecular building block at the
      heart of such a transition which mediates such a process from a single molecule
      to a network. Although a large number of building blocks have created assorted
      materials, utilization of a well-defined coordination complex as the building
      block (i.e., metalloligand) is unique for the construction of a designed
      architecture. A coordination complex as the building block offers structural
      rigidity that places the auxiliary functional groups to a pre-organized
      conformation. Such auxiliary functional groups could then coordinate a secondary
      metal ion or be involved in the self-assembly via weak interactions, such as
      hydrogen bonds. This review focuses on the recent progress achieved through
      assorted molecular building blocks towards generating ordered networks. Broadly,
      two classes of metalloligands will be discussed: those offering hydrogen bond
      sensitive functional groups and those tendering coordination bond responsive
      groups. Nevertheless, the result is the construction of networks of a highly
      ordered nature in both cases. The present review is expected to provide new
      strategies for constructing functional materials through metalloligands for
      challenging and practical applications. 

PMID- 24081026
TI  - A surgical technique for homogenous renal distribution of substances in rats.
AB  - Intra-arterial injection of mesenchymal stem cells has been proven to result in a
      superior nephroprotection compared to intravenous injection. This avoids initial
      passage through filter organs such as the lung, liver and spleen. The aim of the
      present study was to investigate whether suprarenal aortic delivery results in a
      homogenous distribution to both kidneys. Chinese ink was used to evaluate the
      renal distribution pattern for the comparison of two retrograde intra-aortic
      injection methods. In the first, the aorta caudal to the renal branches was
      temporarily clamped and Chinese ink was injected at the level of the renal
      arteries. In the second, a distal aortic clamp was combined with alternated
      clamping of the contralateral arteries. Immediately after injection, kidneys were
      harvested for histological analysis. Amniotic fluid stem cells labeled with LacZ
      were injected in the aorta by alternated clamping of the renal arteries in order
      to track the cells in a rat ischemia/reperfusion model. Without renal artery
      clamping, intra-aortic administration resulted in a delivery of the ink into the
      right kidney, whereas administration with alternated clamping of the
      contralateral renal artery, together with distal aortic artery clamping, resulted
      in a more homogenous distribution of the ink in both kidneys. Moreover, LacZ
      positive cells were found in both kidneys after 6 h of injection. In conclusion,
      the retrograde administration of Chinese ink in two steps is a fast and
      reproducible technique, which results in a more homogenous distribution of the
      stain in both kidneys than a single administration combined by only clamping the
      aorta.

PMID- 24081028
TI  - A new technique for the assessment of the 3D spatial distribution of the
      calcium/phosphorus ratio in bone apatite.
AB  - The value and distribution of calcium/phosphorus (Ca/P) ratio in bone vary
      between healthy and osteoporotic bone. The purpose of this study was the
      development of a technique for the assessment of the 3D spatial distribution of
      Ca/P ratio in bone apatite, which could eventually be implemented through a
      conventional computed tomography (CT) system. A three-material mass-fraction
      decomposition CT dual energy analysis was optimized. The technique was validated
      using ten bone phantoms of different, known Ca/P ratio. Their measured average
      Ca/P ratio showed a mean/maximum deviation from the expected Ca/P ratio of
      0.24/0.35. Additionally, three healthy and three inflammation-mediated
      osteoporotic (IMO) collagen-free rabbit tibia bone samples were assessed,
      providing promising preliminary results on real bone tissue. The average Ca/P
      ratios in all IMO samples (1.64-1.65) were found to be lower than in healthy
      samples (1.67-1.68). Osteoporotic regions in IMO samples were located using Ca/P
      ratio colour maps and Ca/P ratio values as low as 1.40 +/- 0.26 were found. The
      low Ca/P ratio volume proportion in IMO samples (12.8%-13.9%) was found to be
      higher than in healthy (5.8%-8.3%) samples. A region growing technique showed a
      higher homogeneity of Ca/P ratio in healthy than in IMO bone samples. 

PMID- 24081030
TI  - Managing the human toll caused by seasonal influenza: New York State's mandate to
      vaccinate or mask.

PMID- 24081031
TI  - Phase measurements on terahertz waves.
AB  - The change in phase of the free space terahertz (THz) electric field as a sample
      of material introduced into the THz beampath of a CW THz system is measured and
      used to calculate the index of refraction of materials at 250 GHz. 

PMID- 24081032
TI  - Middle infrared active coherent laser spectrometer for standoff detection of
      chemicals.
AB  - Using a quantum cascade laser emitting at 7.85 MUm, a middle infrared active
      coherent laser spectrometer has been developed for the standoff detection of
      vapor phase chemicals. The first prototype has been tested using diffuse target
      backscattering at ranges up to ~30 m. Exploiting the continuous frequency tuning
      of the laser source, spectra of water vapor, methane, nitrous oxide, and hydrogen
      peroxide were recorded. A forward model of the instrument was used to perform
      spectral unmixing and retrieve line-of-sight integrated concentrations and their
      one-sigma uncertainties. Performance was found to be limited by speckle noise
      originating from topographic targets. For absorbers with large absorption cross
      sections such as nitrous oxide (>10(-19) cm(2).molecule(-1)), normalized
      detection sensitivities range between 14 and 0.3 ppm.m.Hz(-1/2), depending on the
      efficiency of the speckle reduction scheme implemented.

PMID- 24081029
TI  - Inactive ERBB receptors cooperate with reactive oxygen species to suppress cancer
      progression.
AB  - The ERBB receptors are a family of heterodimerization partners capable of driving
      transformation and metastasis. While the therapeutic targeting of single
      receptors has proven efficacious, optimal targeting of this receptor family
      should target all oncogenic members simultaneously. The juxtamembrane domains of
      ERBB1, ERBB2, and ERBB3 are highly conserved and control various aspects of ERBB
      dependent biology. In an effort to block those functions, we have targeted this
      domain with decoy peptides synthesized in tandem with a cell-penetrating peptide,
      termed EJ1. Treatment with EJ1 induces cell death, promotes the formation of
      inactive ERBB multimers, and results in simultaneous reduction of ERBB1, ERBB2,
      and ERBB3 activation. Treatment also results in the activation of myosin light
      chain-dependent cell blebbing while inactivating CaMKII signaling, coincident
      with the induction of cell death. EJ1 also directly translocates to mitochondria,
      correlating with a loss of mitochondrial membrane potential and production of
      reactive oxygen species. Finally, treatment of a mouse model of breast cancer
      with EJ1 results in the inhibition of tumor growth and metastasis without
      associated toxicities in normal cells. Overall, these data demonstrate that a
      portion of the ERBB jxm domain, when used as an intracellular decoy, can inhibit
      tumor growth and metastasis, representing a novel anticancer therapeutic.

PMID- 24081033
TI  - Approach to multiparticle parallel tracking in thick samples with three
      dimensional nanoresolution.
AB  - This Letter proposes a method referred to as distorted grating (DG) and double
      helix point spread function (DH-PSF) combination microscopy (DDCM), which is
      capable of multiparticle parallel localization and tracking in a transparent
      sample thicker than 10 MUm, the thickness of cells. A special phase mask,
      combining the field depth extension capabilities of DG with the three-dimensional
      (3D) nanolocalization capabilities of the DH-PSF, is designed for multiparticle
      parallel localization. Time-lapse tracking of one particle moving along the z
      axis and parallel tracking of two particles are simulated. Results demonstrate
      that, with only a single snapshot, particles can be localized, tracking with 3D
      nanoresolution wherever they are. The theoretical localization precisions of
      DDCM, DH-PSF, and multifocus microscopy are compared. DDCM results in almost
      constant localization precisions in all three dimensions for a depth of field
      larger than 10 MUm. DDCM is expected to become a tool in investigations of
      important dynamic events in living cells. 

PMID- 24081034
TI  - Zak phase of photons in optical waveguide lattices.
AB  - Zak phase, that is, the Berry phase acquired during an adiabatic motion of a
      Bloch particle across the Brillouin zone, provides a measure of the topological
      invariant of Bloch bands in one-dimensional crystalline potentials. Here a
      photonic structure, based on engineered lattices of evanescently coupled optical
      waveguides, is proposed to detect Zak phase difference of photons undergoing
      Bloch oscillations in topologically distinct Bloch bands of dimerized
      superlattices. 

PMID- 24081035
TI  - Simultaneous quantum dash-well emission in a chirped dash-in-well
      superluminescent diode with spectral bandwidth >700 nm.
AB  - We report on the quantitative evidence of simultaneous amplified spontaneous
      emission from the AlGaInAs/InAs/InP-based quantum-well (Qwell) and quantum-dashes
      (Qdash) in a multistack dash-in-an-asymmetric-well superluminescent diode
      heterostructure. As a result, an emission bandwidth (full width at half-maximum)
      of >700 nm is achieved, covering entire O-E-S-C-L-U communication bands, and a
      maximum continuous wave output power of 1.3 mW, from this device structure. This
      demonstration paves a way to bridge entire telecommunication bands through proper
      optimization of device gain region, bringing significant advances and impact to a
      variety of cross-disciplinary field applications.

PMID- 24081036
TI  - Photonic-integrated circuit for continuous-wave THz generation.
AB  - We demonstrate a photonic-integrated circuit for continuous-wave (cw) terahertz
      (THz) generation. By comprising two lasers and an optical phase modulator on a
      single chip, the full control of the THz signal is enabled via a unique
      bidirectional operation technique. Integrated heaters allow for continuous tuning
      of the THz frequency over 570 GHz. Applied to a coherent cw THz photomixing
      system operated at 1.5 MUm optical wavelength, we reach a signal-to-noise ratio
      of 44 dB at 1.25 THz, which is identical to the performance of a standard system
      based on discrete components. 

PMID- 24081037
TI  - Light scattering in disordered honeycomb photonic lattices near the Dirac points.
AB  - We address Anderson localization in disordered honeycomb photonic lattices and
      show that the localization process is strongly affected by the spectral position
      of the input wavepacket within the first Brillouin zone of the lattice. In spite
      of the fact that in regular lattices expansion of the beam is much stronger for
      excitation near the Dirac points-where light exhibits conical diffraction-than
      for excitation at the center of the Brillouin zone-where light exhibits normal
      diffraction-we found that disorder leads to pronounced Anderson localization even
      around the Dirac points. We found that for the same disorder level the width of
      the averaged output intensity distribution for excitations around the Dirac
      points may be substantially larger than that for excitations at the center of the
      Brillouin zone. 

PMID- 24081038
TI  - Upconversion emissions induced by 1550 nm in near-stoichiometric Er:LiNbO3
      crystal.
AB  - To increase the photovoltaic efficiency of solar cells, green and red
      upconversion (UC) emissions produced at an excitation of 1550 nm were
      investigated. A drastically enhanced red UC emission was observed in near
      stoichiometric LiNbO(3) crystal heavily doped with Er(3+) ions (Er:NSLN). Raman
      spectra showed that the maximum phonon energy shifted from 631 cm(-1) in Er(3+)
      doped congruent LiNbO(3) (Er:CLN) to 871 cm(-1) in Er:NSLN crystal. The time
      decay of the (4)S(3/2)->(4)I(15/2) transition suggested that the Er(3+) cluster
      sites (Er(Li)(2+)-Er(Nb)(2-)) were dissociated in the Er:NSLN crystal. The
      visible UC luminescence converted from near infrared at the wavelength of 1550 nm
      was important to enlarge the solar spectrum response of solar cell.

PMID- 24081039
TI  - High-order all-optical differential equation solver based on microring
      resonators.
AB  - We propose and experimentally demonstrate a feasible integrated scheme to solve
      all-optical differential equations using microring resonators (MRRs) that is
      capable of solving first- and second-order linear ordinary differential equations
      with different constant coefficients. Employing two cascaded MRRs with different
      radii, an excellent agreement between the numerical simulation and the
      experimental results is obtained. Due to the inherent merits of silicon-based
      devices for all-optical computing, such as low power consumption, small size, and
      high speed, this finding may motivate the development of integrated optical
      signal processors and further extend optical computing technologies. 

PMID- 24081040
TI  - Monolithic bifocal zone-plate lenses for confocal collimation of laser diodes.
AB  - An elliptical monolithic bifocal zone plate as a collimating lens, whose two
      focal lengths in the orthogonal directions match the different beam waist
      positions of the fast and slow axes' light from edge-emitting laser diodes, is
      proposed and experimentally demonstrated by employing femtosecond laser direct
      writing technology. The high-quality eight-level zone plate exhibits a
      diffraction efficiency of 92.9%, which is much higher than those ever reported.
      Shaped by the elliptical lens, the laser diodes' divergence angles are
      simultaneously reduced from 65 degrees  (1134 mrad, fast axis) and 24 degrees 
      (418 mrad, slow axis) to 7.7 and 136.5 mrad, respectively. 

PMID- 24081041
TI  - Femtosecond laser-induced periodic structure adjustments based on electron
      dynamics control: from subwavelength ripples to double-grating structures.
AB  - This study proposes a method for adjusting subwavelength ripple periods and the
      corresponding double-grating structures formed on fused silica by designing
      femtosecond laser pulse trains based on localized transient electron density
      control. Four near-constant period ranges of 190-490 nm of ripples perpendicular
      to the polarization are obtained by designing pulse trains to excite and modulate
      the surface plasmon waves. In the period range of 350-490 nm, the double-grating
      structure is fabricated in one step, which is probably attributable to the
      grating-assisted enhanced energy deposition and subsequent thermal effects. 

PMID- 24081042
TI  - Ultraviolet four-wave mixing in the LP(02) fiber mode.
AB  - We report UV four-wave mixing in the LP(02) mode of a photonic crystal fiber when
      pumped by a frequency-doubled 532 nm microchip laser in the normal dispersion
      regime. A pure LP(02) mode was generated for the pump light by a broadband all
      fiber mode converter. Ultraviolet signal wavelengths as short as 342 nm were
      generated.

PMID- 24081043
TI  - Wavelength-division-multiplexing method of polarized low-coherence interferometry
      for fiber Fabry-Perot interferometric sensors.
AB  - We propose a new wavelength-division-multiplexing method for extrinsic fiber
      Fabry-Perot interferometric (EFPI) sensing in a polarized low-coherence
      interferometer configuration. In the proposed method, multiple LED sources are
      used with different center wavelengths, and each LED is used by a specific
      sensing channel, and therefore the spatial frequency of the low-coherence
      interferogram of each channel can be separated. A bandpass filter is used to
      extract the low-coherence interferogram of each EFPI channel, and thus the cavity
      length of each EFPI channel can be identified through demultiplexing. We
      successfully demonstrate the simultaneous demodulation of EFPI sensors with same
      nominal cavity length while maintaining high measurement precision. 

PMID- 24081044
TI  - Magnetic field induced great photoluminescence enhancement in an Er3+:YVO4 single
      crystal used for high magnetic field calibration.
AB  - An optical technique is proposed for the accurate calibration of pulsed high
      magnetic fields utilizing the magnetic field dependent photoluminescence (PL)
      properties in an Er(3+):YVO(4) single crystal at 80 K. Bright green PL emissions
      are excited by a 487.5 nm laser line and can be enhanced greatly by a magnetic
      field at certain field values (B(c)). Since the B(c)'s under 10 T are extremely
      stable for a given sample at a certain temperature, and the FWHM of the
      enhancement peaks are less than 0.9 T, an Er(3+):YVO(4) single crystal is proven
      to be a good candidate for pulsed high magnetic field calibration. The detailed
      processes and numerous advantages of the technique are presented in this work.

PMID- 24081045
TI  - Simultaneous broadband Raman cascading and parametric conversion in potassium
      titanyl phosphate.
AB  - We generated a broad spectrum of light between 1064 and 1300 nm in the infrared
      by cascading stimulated Raman scattering in a potassium titanyl phosphate crystal
      while broadband conversion of the infrared Raman cascade was simultaneously
      achieved in the visible through second-harmonic generation (SHG) and sum
      frequency mixing. We observed that odd- and even-order cascaded Stokes components
      were spatially addressed at different angles of propagation in the crystal. The
      efficiency of SHG and sum-frequency mixing is discussed as a function of the pump
      polarization. We also report on significant spatial distortions of the output
      Stokes beams. 

PMID- 24081046
TI  - Simultaneous and precise fault locating in WDM-PON by the generation of optical
      wideband chaos.
AB  - We demonstrate a simple approach to generating optical wideband chaos and verify
      that it can be used to locate simultaneously and precisely the faults among all
      branches in a wavelength-division-multiplexing (WDM) passive optical network
      (PON). The chaotic light source consists of a semiconductor optical amplifier
      ring structure with an output optical 3 dB bandwidth of above 60 nm covering the
      whole C-band. This kind of optical wideband chaos can be naturally filtered by
      the WDM devices in the PON. Each filtering light signal along the corresponding
      branch retains good chaotic characteristics We demonstrate a proof-of-concept
      experiment for the detection of three International Telecommunication Union
      channels. The experimental measurements show that a much higher spatial
      resolution of 1.66 cm and a dynamic range of about 10.1 dB are achieved. 

PMID- 24081047
TI  - Magnetic field sensing based on singlemode-multimode-singlemode fiber structures
      using magnetic fluids as cladding.
AB  - Magnetic field sensing based on magnetic fluid (MF) and a singlemode-multimode
      singlemode (SMS) fiber structure is proposed. The sensitivity of the proposed
      sensing system can be enhanced by corroding the cladding of the multimode fiber
      of the SMS fiber structure. The achieved maximum magnetic field sensitivity of
      our experimental structures is -16.86 pm/Oe as the fiber is corroded for 1680 s.
      The visibility of the interference dip for the MF-clad SMS fiber structure
      decreases with corrosion time. Considering the trade-off between sensitivity and
      visibility, the figure of merit of the sensing system is employed to evaluate the
      sensing performance comprehensively. In our experiments, the structure corroded
      for ~1620 s is found to have maximum sensing performance.

PMID- 24081048
TI  - Highly photosensitive polymethyl methacrylate microstructured polymer optical
      fiber with doped core.
AB  - In this Letter, we report the fabrication of a highly photosensitive,
      microstructured polymer optical fiber using benzyl dimethyl ketal as a dopant, as
      well as the inscription of a fiber Bragg grating in the fiber. A refractive index
      change in the core of at least 3.2*10(-4) has been achieved, providing a grating
      with a strong transmission rejection of -23 dB with an inscription time of only
      13 min. The fabrication method has a big advantage compared to doping step index
      fiber since it enables doping of the fiber without using extra dopants to
      compensate for the index reduction in the core introduced by the photosensitive
      agent.

PMID- 24081049
TI  - Enhancement of outcoupling efficiency of organic light-emitting diodes using a
      planarized moth-eye structure on glass substrate.
AB  - To improve optical properties of organic light-emitting diodes (OLEDs), we
      developed a planarized moth-eye structure by ultraviolet nanoimprint lithography
      (UV-NIL). The moth-eye pattern was fabricated on a glass substrate by UV-NIL
      using AMONIL polymer resin. It contains nanoscaled, cone-shaped, periodic pattern
      arrays with a 250 nm diameter and a 550 nm pitch. The glass substrate with the
      moth-eye structure exhibited a 1%-2% improvement in transmittance of visible
      wavelengths, but it requires a planarized layer with high-refractive-index
      materials. Photosensitive titanium precursor resin annealed by UV was used to
      improve the current efficiency by up to 26% versus conventional OLEDs. 

PMID- 24081050
TI  - Highly efficient nanofocusing in a single step-like microslit.
AB  - Highly efficient plasmonic nanofocusing is numerically predicted in a single step
      like microslit, which is placed on a high-index dielectric layer. Because of the
      high throughput of the impinging light on the wide microslit, highly efficient
      nanofocusing is achieved in the proposed structure based on the multimode
      interferences in the microslits, the constructive interference between the
      transmitted light and the scattered surface plasmon polaritons, and the Fabry
      Perot resonator effect in the high-index dielectric layer. Compared with previous
      nanofocusing structures containing plenty of substructures arranged laterally,
      the proposed structure has a much smaller lateral dimension because of the
      vertical arrangement of the microslits. This is of importance for realizing
      densely integrated plasmonic circuits. 

PMID- 24081051
TI  - Photoluminescence of a Te4+ center in zinc borate glass.
AB  - Photoluminescent (PL) properties related to Te(4+) species in zinc borate glasses
      are examined. Broad emission was observed by the excitation of the PL excitation
      peak of Te(4+) present at the optical absorption edge. The emission intensity of
      Te(4+) in 5TeO(2)-50ZnO-45B(2)O(3) glass was thermally quenched in a temperature
      region over 100 K, suggesting that concentration quenching preferentially
      occurred. The lifetime of the emission was approximately 2.5 MUs, which is
      characteristic of relaxation from the triplet excitation state of an ns(2)-type
      center.

PMID- 24081052
TI  - Robustness of antenna-coupled distributed bolometers.
AB  - This Letter shows the effect of the geometrical and material properties of lead
      lines and connections on the robustness and reliability of optical antennas
      working as distributed bolometers. We analyze the operational limits of the
      biasing voltage using a mutiphysics finite element method. We demonstrate that,
      after evaluating the effect of the electromagnetic irradiance falling on the
      device, biasing voltage is the main limiting factor to maintain operative
      titanium optical antennas. Results have been experimentally verified by finding
      the biasing values needed to destroy optical antennas working as distributed
      bolometers. Structural damage has been identified from scanning electron
      microscopy images. 

PMID- 24081053
TI  - Actively Q-switched compact Yb:YSGG laser generating 3.1 mJ of pulse energy.
AB  - An efficient compact Yb:Y(3)Sc(1.5)Ga(3.5)O(12) garnet crystal laser actively Q
      switched with an acousto-optic modulator is demonstrated, producing stable pulses
      at repetition rates ranging from 1 to 30 kHz. With 10.8 W of pump power absorbed,
      an average output power of 3.1 W at 1025.7 nm is generated at pulse repetition
      rate of 1 kHz, with a slope efficiency of 46%. The resulting pulse energy,
      duration, and peak power are 3.1 mJ, 23.9 ns, and 130 kW, respectively.

PMID- 24081054
TI  - Visible light communications using a directly modulated 422 nm GaN laser diode.
AB  - Visible light communications using a Gallium-nitride (GaN) laser diode is
      reported. Devices, which are cased in TO packages, show modulation bandwidths of
      up to 1.4 GHz. We demonstrate error-free data transmission, defined as
      transmission of 1*10(-9) bits without any errors, at 2.5 Gbit/s with a
      sensitivity of 11.5 dBm.

PMID- 24081055
TI  - Low-temperature sensitivity periodically tapered photonic crystal-fiber-based
      refractometer.
AB  - In this Letter, an all-fiber refractometer with a simple configuration of
      periodical tapers on a photonic crystal fiber (PCF) is proposed and investigated
      experimentally. The proposed fiber refractive index (RI) sensor consists of a PCF
      sandwiched between two standard single-mode fibers, with tapers periodically
      fabricated along the PCF using a CO(2) laser beam focused by a ZnSe cylindrical
      lens. The proposed fiber sensor can be used for RI sensing by measuring the
      wavelength shift of the multimode interference dip over the transmission
      spectrum. An average sensitivity of 222 nm/RIU has been experimentally achieved
      over a RI range from 1.33 to 1.38. The proposed refractometer is also
      significantly less sensitive to temperature, and an experimental demonstration of
      this reduced sensitivity is presented. The proposed RI sensor benefits from
      simplicity and low-cost and achieves a competitive sensitivity compared with
      other existing fiber-optic sensors.

PMID- 24081056
TI  - Multiplexed detection of xylene and trichloroethylene in water by photonic
      crystal absorption spectroscopy.
AB  - We experimentally demonstrate simultaneous selective detection of xylene and
      trichloroethylene (TCE) using multiplexed photonic crystal waveguides (PCWs) by
      near-infrared optical absorption spectroscopy on a chip. Based on the slow light
      effect of photonic crystal structure, the sensitivity of our device is enhanced
      to 1 ppb (v/v) for xylene and 10 ppb (v/v) for TCE in water. Multiplexing is
      enabled by multimode interference power splitters and Y-combiners that integrate
      multiple PCWs on a silicon chip in a silicon-on-insulator platform. 

PMID- 24081057
TI  - Formation and dynamics of a toroidal bubble during laser propelling a cavity
      object in water.
AB  - We captured stable self-oscillations of a toroidal bubble moving away from a
      laser propelled cavity object in water using a high-speed imaging system. The
      entire laser propelling process generates a hemispherical bubble, two toroidal
      bubbles, and a microbubble cluster. The hemispherical bubble is formed by laser
      breakdown in water. The toroidal bubbles are formed by the variation of the
      pressure field as a result of the propagation, reflection, and convergence of the
      laser plasma shockwave in the cavity. 

PMID- 24081058
TI  - Four-wavelength microdisk laser array laterally coupled with a bus waveguide.
AB  - A four-wavelength microdisk laser array laterally coupled with a bus waveguide is
      demonstrated numerically and experimentally. The coupled-mode characteristics as
      well as scattering loss in the bus waveguide caused by the connected microdisks
      are simulated by a 2D finite-difference time-domain technique. An AlGaInAs/InP
      microdisk laser array with circular radii of 10.1, 10.2, 10.3, and 10.4 MUm is
      designed and fabricated by common photolithography and an inductively coupled
      plasma etching technique. Continuous-wave electrically injected operation is
      realized at room temperature with the lowest threshold current of 3 mA. Four
      wavelength lasing operation is realized with wavelength intervals of 3-4 nm and
      side mode suppression ratios larger than 25 dB. Finally, the influences of
      heating effect and thermal cross talk on lasing mode wavelength tuning are
      investigated experimentally. 

PMID- 24081059
TI  - Atomic wave-packet dynamics and third-harmonic generation in sodium.
AB  - In femtosecond degenerate four-wave mixing experiments in sodium vapor, quantum
      beats are observed at the wavelength of the third harmonic when the fundamental
      beams are three-photon resonant. The period of beating, which corresponds to fine
      structure energy-level splitting, does not change with the atomic number density,
      buffer gas pressure, or laser intensity. Surprisingly, the third-harmonic signal
      is observed only at negative time delays for the transient grating pulse
      sequence. We relate this to the well-known interference effect between excitation
      pathways involving the fundamental and the third-harmonic fields, which leaves
      atoms virtually unexcited and prevents formation of population grating. 

PMID- 24081060
TI  - Dispersive wave emission from wave breaking.
AB  - We show that pulses undergoing wave breaking in nonlinear weakly dispersive
      fibers radiate, owing to phase-matching (assisted by higher-order dispersion) of
      linear dispersive waves with the shock-wave front. Our theoretical results
      perfectly explain the radiation observed recently from pulses propagating in the
      normal dispersion (i.e., nonsolitonic) regime. 

PMID- 24081061
TI  - Superlens imaging with a surface plasmon polariton cavity in imaging space.
AB  - We investigate the ultradeep subwavelength imaging of a superlens with a surface
      plasmon polariton (SPP) cavity. A silver layer is added in the imaging region of
      the superlens to form an Ag film lens/photoresist/Ag layer cavity, in which the
      long-range plasmon mode is drastically suppressed and the field of the imaging is
      significantly amplified and extended over to the entire imaging region due to the
      SPP resonance inside the cavity. Results show that much improved quality of image
      with much suppressed sidelobes and much extended depth of focus can be obtained
      with the cavity structure when compared with the conventional open structure.
      This is confirmed by the transfer function of the system, which becomes flatter
      with the cavity structure. The proposed method provides a novel and practically
      feasible way to achieve images with both high resolution and large depth of
      field. 

PMID- 24081062
TI  - Organic ultraviolet photodetector based on phosphorescent material.
AB  - A new type of organic visible-blind UV-PDs is demonstrated by utilizing
      phosphorescent material Ir(III)bis[(4,6-difluorophenyl)-pyridinato-N, C(2)']
      picolinate (FIrpic) as the electron donor and [6,6]-phenyl-C-61
      butyricacidmethylester (PCBM) as the electron accepter, respectively. The peak
      responsivity of the organic UV-PDs is as high as 140 mA/W, corresponding to an
      external quantum efficiency of about 48%, under 365 nm UV light with an intensity
      of 0.018 mW/cm(2). The distinct photoluminescence quenching of FIrpic is obtained
      by doping PCBM. The organic UV-PDs provide visible-blind performance with the
      strong photocurrent response in the UV-A region, the rise and fall times of less
      than one second, and linear response within the incident light-intensity range
      from 0.018 to 20 mW/cm(2).

PMID- 24081063
TI  - Active directional beaming by mechanical actuation of double-sided plasmonic
      surface gratings.
AB  - A novel mechanism for active directional beaming by mechanical actuation of
      double-sided plasmonic surface gratings is proposed. It is shown that the
      asymmetric mechanical actuation of optimally designed plasmonic surface gratings
      surrounding a subwavelength metal slit can produce a steerable off-axis beaming
      effect. The controllability of the beam direction provides an opportunity to
      develop novel active plasmonic devices and systems. 

PMID- 24081064
TI  - Limits of imaging-system simplification using cubic mask wavefront coding.
AB  - Increasing the space-bandwidth product of an imaging system will lead to a
      complex and expensive optical system. Techniques exist to simplify imaging
      systems. We propose the use of a hybrid imaging system using pupil phase
      modulation. Based on the reconstructed image's mean-squared error, we compute how
      this error is affected under various third-order aberrations. We determine the
      best cubic phase-mask parameter and study the impact of the orientation of the
      coma and astigmatism, as we have in a real optical system (from 0 to 2pi). We
      then compute how the reconstructed image's quality varies by adding defocus
      related aberrations (defocus and/or field curvature). Based on our analysis, we
      determine the limits of a hybrid imaging system using a cubic phase mask to
      develop simplified imaging systems. We conclude that the simplified lens design
      can be corrected if its aberrations are limited to 1 lambda of coma, astigmatism,
      and spherical aberrations and less than 1 lambda of field curvature or defocus. 

PMID- 24081065
TI  - Measuring optically thick molecular samples using chirped laser dispersion
      spectroscopy.
AB  - In this Letter, a dispersion-based gas sensing method applied to detection of
      optically thick samples is presented. We show that chirped laser dispersion
      spectroscopy (CLaDS) technique provides perfectly linear signal response over a
      wide range of target analyte concentrations. Using the most convenient chirp
      modulated CLaDS detection scheme, it enables spectroscopic measurements in a line
      locked mode from the minimum detection limit up to >99% peak molecular
      absorption. 

PMID- 24081066
TI  - Coupling of single quantum emitters to plasmons propagating on mechanically
      etched wires.
AB  - We demonstrate the coupling of a single nitrogen vacancy center in a nanodiamond
      to propagating plasmonic modes of mechanically etched silver nanowires. The
      mechanical etch is performed on single crystalline silver nanoplates by the tip
      of an atomic force microscope cantilever to produce wires with pre-designed
      lengths. We show that single plasmon propagation can be obtained in these wires,
      thus making these structures a platform for quantum information processing. 

PMID- 24081067
TI  - SESAM mode-locked Yb:CaGdAlO4 thin disk laser with 62 fs pulse generation.
AB  - We present a semiconductor saturable absorber mirror (SESAM) mode-locked thin
      disk laser (TDL) based on Yb:CaGdAlO(4) (Yb:CALGO) generating 62 fs pulses, which
      is the shortest pulse duration achieved from mode-locked TDLs to date. The
      oscillator operates at a repetition rate of 65 MHz and delivers 5.1 W of average
      output power. The short pulse duration of our TDL in combination with the high
      intracavity peak power of 44 MW makes this oscillator attractive for intracavity
      table-top extreme nonlinear optics applications such as high harmonic generation
      and vacuum ultraviolet frequency comb generation. The current average power was
      limited by the quality of the Yb:CALGO disk. However, power scaling of Yb:CALGO
      TDLs to the multi-10-W range with short pulse durations (<100 fs) appears
      feasible in the near future by using thinner disks of better quality and further
      optimized SESAMs.

PMID- 24081068
TI  - Tunable optical parametric amplification characteristics of liquid-filled
      chalcogenide photonic crystal fibers.
AB  - A new technique to attain tunable parametric amplification in photonic crystal
      fibers (PCFs) through control of chromatic dispersion is proposed and empirically
      investigated. By infiltrating the air channels of the PCFs with suitable thermo
      optic liquids, the zero-dispersion wavelength (ZDW) can be tailored to provide a
      wider gain spectrum in the mid-IR range and generate blueshifted frequency
      components. It is deduced that a change of 10-20 nm in the ZDW around the pump
      creates a gain region several hundred nanometers from the pump wavelength by only
      varying the temperature of the liquid externally. 

PMID- 24081069
TI  - Efficient inscription of Bragg gratings in As2S3 fibers using near bandgap light.
AB  - Efficient inscription of Fiber Bragg gratings (FBGs) in single-mode, thin
      cladding As(2)S(3) fibers is demonstrated by using near bandgap light at 532 nm.
      The FBGs with the reflectivity of over 80% can be induced in only 80-90 s,
      substantially faster than in previous reports. The dynamics of the grating growth
      are investigated in the photosensitivity process, showing a fast blue shift of
      the Bragg wavelength and then a somewhat slower red shift. The aging of the
      grating after fabrication is also reported, indicating a 37% decay of the grating
      strength.

PMID- 24081070
TI  - Exciton quenching by diffusion of 2,3,5,6-tetrafluoro-7,7',8,8'-tetra cyano quino
      dimethane and its consequences on joule heating and lifetime of organic light
      emitting diodes.
AB  - In this Letter, the effect of F(4)-TCNQ insertion at the anode/hole transport
      layer (HTL) interface was studied on joule heating and the lifetime of organic
      light-emitting diodes (OLEDs). Joule heating was found to reduce significantly
      (pixel temperature decrease by about 10 K at a current density of 40 mA/cm(2)) by
      this insertion. However, the lifetime was found to reduce significantly with a 1
      nm thick F(4)-TCNQ layer, and it improved by increasing the thickness of this
      layer. Thermal diffusion of F(4)-TCNQ into HTL leads to F(4)-TCNQ ionization by
      charge transfer, and drift of these molecules into the emissive layer caused
      faster degradation of the OLEDs. This drift was found to reduce with an increase
      in the thickness of F(4)-TCNQ.

PMID- 24081071
TI  - Efficient method for controlling the spatial coherence of a laser.
AB  - An efficient method to tune the spatial coherence of a degenerate laser over a
      broad range with minimum variation in the total output power is presented. It is
      based on varying the diameter of a spatial filter inside the laser cavity. The
      number of lasing modes supported by the degenerate laser can be controlled from 1
      to 320,000, with less than a 50% change in the total output power. We show that a
      degenerate laser designed for low spatial coherence can be used as an
      illumination source for speckle-free microscopy that is nine orders of magnitude
      brighter than conventional thermal light. 

PMID- 24081072
TI  - Ultraweak background scattered light reveals structure of a diffractive element.
AB  - Background scattered light should normally be reduced in industrial fabrication
      processes; however, we demonstrated that background scattered light from an
      optical element contains significant structural information about the element.
      This was revealed by quite good agreement between the measured scattering
      intensity distribution of a sample and a computer simulation of the light
      intensity from the sample. The intensity distribution from a carefully fabricated
      sample with artificially controlled defects was obtained with a measurement
      system designed to measure ultraweak background scattered light covering an
      intensity range of over 10(10).

PMID- 24081073
TI  - Nonlinear compression to sub-30-fs, 0.5 mJ pulses at 135 W of average power.
AB  - Incorporation of coherent combination into a state-of-the-art fiber-chirped pulse
      amplification system obtains 1.1 mJ, 340 fs pulses with up to 280 W of average
      power at 250 kHz repetition rate. Propagation of this laser pulse inside a
      krypton-filled hollow-core fiber results in significant spectral broadening.
      Chirped mirrors are used to compress the pulses to 26 fs, 540 MUJ (135 W) leading
      to a peak power of more than 11 GW. This unprecedented combination of high peak
      and average power ultrashort pulses opens up new possibilities in
      multidimensional surface science and coherent soft x-ray generation. 

PMID- 24081074
TI  - PPLN-based OOK and DQPSK optical grooming by amplitude and phase-signal
      multiplexing through pump depletion.
AB  - We propose and characterize a simple, integrable, and wavelength-preserving
      scheme able to groom a 40 Gbps (D)QPSK signal with a 20 Gbps OOK one into a 20
      Gbaud (60 Gbps) 8-APSK signal. The proposed all-optical scheme is based on the
      second-order nonlinear signal-depletion effect in a single periodically poled
      lithium niobate (PPLN) waveguide. Performance of the device, characterized by
      means of BER measurements, attests error-free operation and a power penalty below
      4.1 dB. 

PMID- 24081075
TI  - Triple Wollaston-prism complete-Stokes imaging polarimeter.
AB  - Imaging polarimetry is emerging as a powerful tool for remote sensing in space
      science, Earth science, biology, defense, national security, and industry.
      Polarimetry provides complementary information about a scene in the visible and
      infrared wavelengths. For example, surface texture, material composition, and
      molecular structure will affect the polarization state of reflected, scattered,
      or emitted light. We demonstrate an imaging polarimeter design that uses three
      Wollaston prisms, addressing several technical challenges associated with moving
      remote-sensing platforms. This compact design has no moving polarization elements
      and separates the polarization components in the pupil (or Fourier) plane,
      analogous to the way a grating spectrometer works. In addition, this concept
      enables simultaneous characterization of unpolarized, linear, and circular
      components of optical polarization. The results from a visible-wavelength
      prototype of this imaging polarimeter are presented, demonstrating remote
      sensitivity to material properties. This work enables new remote sensing
      capabilities and provides a viable design concept for extensions into infrared
      wavelengths. 

PMID- 24081076
TI  - Measurements of the refractive indices and thermo-optic coefficients of Si3N4 and
      SiO(x) using microring resonances.
AB  - We present a method for determining the core and cladding refractive indices of a
      microring resonator from its measured quasi-transverse electric and magnetic
      resonant modes. We use single wavelength reflective microrings to resolve the
      azimuthal order ambiguity of the measured resonances. We perform accurate
      electromagnetic simulations to model the dependence of the resonances on
      geometrical and material parameters. We linearize the model and use the singular
      value decomposition method to find the best fit parameters for the measured data.
      At 1550 nm, we determine n(Si(3)N(4))=1.977+/-0.003 for stoichiometric silicon
      nitride deposited using low-pressure chemical vapor deposition (LPCVD) technique
      and n(SiO(x))=1.428+/-0.011 for plasma-enhanced chemical vapor deposition (PECVD)
      oxide. By measuring the temperature sensitivities of microring resonant modes
      with different polarizations, we find the thermo-optic coefficient of the
      stoichiometric silicon nitride to be dn(Si(3)N(4))/dT=(2.45+/-0.09)*10(-5) (RIU/
      degrees C) and the PECVD oxide to be dn(SiO(x))/dT=(0.95+/-0.10)*10(-5) (RIU/
      degrees C).

PMID- 24081077
TI  - Calibration-free in vivo transverse blood flowmetry based on cross correlation of
      slow time profiles from photoacoustic microscopy.
AB  - We propose a cross-correlation-based method to measure blood-flow velocity by
      using photoacoustic microscopy. Unlike in previous autocorrelation-based methods,
      the measured flow velocity here is independent of particle size. Thus an absolute
      flow velocity can be obtained without calibration. We first measured the flow
      velocity ex vivo, using defibrinated bovine blood. Then flow velocities in
      vessels with different structures in a mouse ear were quantified in vivo. We
      further measured the flow variation in the same vessel and at a vessel
      bifurcation. All the experimental results indicate that our method can be used to
      accurately quantify blood velocity in vivo. 

PMID- 24081078
TI  - Topological structures in the Poynting vector field: an experimental realization.
AB  - Experimental measurements of the nonplanar phase of scalar optical beams is
      achieved using polarization singularities and Stokes parameters. The product of
      beam intensity and its phase gradient is calculated to get the Poynting vector
      distribution in the beam cross section. Using these we propose a scheme and
      experimentally obtain generic fundamental spiral, node, and saddle topological
      structures in the Poynting vector field. 

PMID- 24081079
TI  - Optical angular momentum conversion in a nanoslit: comment.
AB  - In a recent work [Opt. Lett.37, 4946 (2012)], the spin-to-orbital optical angular
      momentum conversion from a subwavelength slit having a circular shape has been
      reported. In particular, the conversion efficiency was claimed to be independent
      of the slit dichroism. Here, we correct such a statement and demonstrate that
      dichroism strongly influences the process of optical vortex generation. 

PMID- 24081080
TI  - Optical angular momentum conversion in a nanoslit: reply.
AB  - We respond to a Comment on our Letter [Opt. Lett.37, 4946 (2012)], in which we
      reported on the spin-to-orbital optical angular momentum conversion of a circular
      nanoslit in a thin metal layer. We claimed, in an unfortunately worded sentence,
      that the conversion efficiency was independent of the slit's dichroism, which the
      Comment pointed out was incorrect. We acknowledge this and reiterate our original
      intention that as long as the dichroism is not too large, then it has little
      effect on the conversion efficiency in our system. 

PMID- 24081081
TI  - Experimental study of multiwavelength parametric generation in a two-dimensional
      periodically poled lithium tantalate crystal.
AB  - In this Letter, we experimentally investigate multiwavelength parametric
      generation in two-dimensional second-order nonlinear photonic crystals. For this
      purpose, a 2D periodically poled lithium tantalate crystal with rectangular
      lattice was fabricated and characterized. We demonstrate multiple and
      simultaneous wavelength generation due to the contribution of different lattice
      vectors. Numerical simulations emphasize the agreement of our phase matching
      scheme with the experimental results and made it possible to assign the observed
      wavelengths to the reciprocal lattice vectors involved in the parametric
      generation process. Moreover, our results indicate that some signals are the
      result of the joint contribution of more than one lattice vector. 

PMID- 24081082
TI  - How to distinguish between the annihilation and the creation of optical vortices.
AB  - Optical vortices are always created or annihilated as vortex dipoles-pairs with
      opposite topological charge. Here a quantity, consisting of the transverse first
      and second derivatives of the optical field, is derived with which one can
      distinguish between vortex dipole annihilation and creation events. Analytical
      and numerical examples are provided as a demonstration of the method. 

PMID- 24081083
TI  - Experimental generation of optical flaticon pulses.
AB  - We experimentally investigate the nonlinear reshaping of a continuous wave that
      leads to chirp-free and flat-top intense pulses or flaticons exhibiting strong
      temporal oscillations at their edges and a stable self-similar expansion upon
      propagation of their central region. This study was performed in the normal
      dispersion regime of a nonzero dispersion-shifted fiber and involved a sinusoidal
      phase modulation of the continuous wave. Our fiber optics experiment is analogous
      to considering the collision between oppositely directed currents near the beach,
      and it may open the way to new investigations in the field of hydrodynamics. 

PMID- 24081084
TI  - High efficiency and high peak power picosecond mid-infrared optical parametric
      amplifier based on BaGa4Se7 crystal.
AB  - A high efficiency and high peak power picosecond (ps) mid-infrared optical
      parametric amplifier with a new nonlinear crystal BaGa(4)Se(7) pumped by a 30 ps
      1064 nm Nd:YAG laser is demonstrated for the first time. The maximum photon
      conversion efficiency of 56% from 1064 nm to 3.9 MUm idler has been achieved at
      the pump energy of ~1.8 mJ. A maximum idler output of 830 MUJ at 3.9 MUm with
      peak power of ~27 MW was obtained at pump energy of ~9.1 mJ. Moreover, a 3-5 MUm
      idler tuning range was demonstrated, with output energies of ~300 MUJ at 5 MUm
      and up to 1 mJ at 3 MUm at ~8.2 mJ pump energy.

PMID- 24081085
TI  - Compact Q-value enhanced bandpass filter based on the EIT-like effect
      accompanying application in downconversion APL.
AB  - A compact quality factor (Q)-enhanced bandpass filter based on the
      electromagnetically induced transparency (EIT)-like effect between two-ring
      resonators was proposed and experimental demonstrated. The enhancement in Q can
      be 2-3 orders of magnitude compared to the single ring bandpass filter, and a 27
      times enhanced bandpass filter with a bandwidth of approximately 4.8 GHz was
      successfully realized. A downconversion analog photonic link (APL) based on the
      proposed filter has been presented and the spurious free dynamic range of the
      link was as high as 103.9 dB-Hz(2/3).

PMID- 24081086
TI  - Cluster formation in ferrofluids induced by holographic optical tweezers.
AB  - Holographic optical tweezers were used to show the interaction between a strongly
      focused laser beam and magnetic nanoparticles in ferrofluid. When the light
      intensity was high enough, magnetic nanoparticles were removed from the beam
      center and formed a dark ring. The same behavior was observed when focusing
      vortex or Bessel beams. The interactions between two or more separated rings of
      magnetic nanoparticles created by independent optical traps were also observed. 

PMID- 24081087
TI  - Demonstration of complementary apodized cascaded grating waveguides for tunable
      optical delay lines.
AB  - High-speed, tunable integrated silicon photonic delay lines are demonstrated by
      cascading complementary apodized silicon grating waveguides. The cascaded grating
      waveguides, with inward and outward super-Gaussian apodization profiles,
      compensate each other's dispersion and allow high-speed operation.
      Characterization of the compact delay lines shows that they have low loss, offer
      true time delays of 82 ps and a tuning range of 32 ps, and can potentially
      operate at bit rates as high as 107 Gb/s.

PMID- 24081088
TI  - Carrier-envelope phase stability of hollow fibers used for high-energy few-cycle
      pulse generation.
AB  - We investigated the carrier-envelope phase (CEP) stability of hollow-fiber
      compression for high-energy few-cycle pulse generation. Saturation of the output
      pulse energy is observed at 0.6 mJ for a 260 MUm inner-diameter, 1 m long fiber,
      statically filled with neon. The pressure is adjusted to achieve output spectra
      supporting sub-4-fs pulses. The maximum output pulse energy can be increased to
      0.8 mJ by either differential pumping (DP) or circularly polarized input pulses.
      We observe the onset of an ionization-induced CEP instability, which saturates
      beyond input pulse energies of 1.25 mJ. There is no significant difference in the
      CEP stability with DP compared to static-fill. 

PMID- 24081089
TI  - Faithful reconstruction of digital holograms captured by FINCH using a Hamming
      window function in the Fresnel propagation.
AB  - Recent advances in Fresnel incoherent correlation holography (FINCH) increase the
      signal-to-noise ratio in hologram recording by interference of images from two
      diffractive lenses with focal lengths close to the image plane. Holograms
      requiring short reconstruction distances are created that reconstruct poorly with
      existing Fresnel propagation methods. Here we show a dramatic improvement in
      reconstructed fluorescent images when a 2D Hamming window function substituted
      for the disk window typically used to bound the impulse response in the Fresnel
      propagation. Greatly improved image contrast and quality are shown for simulated
      and experimentally determined FINCH holograms using a 2D Hamming window without
      significant loss in lateral or axial resolution. 

PMID- 24081090
TI  - Nonblocking 4*4 silicon electro-optic switch matrix with push-pull drive.
AB  - A compact rearrangeable nonblocking 4*4 silicon electro-optic switch matrix based
      on a Spanke-Benes network is proposed and fabricated by a 0.18 MUm standard
      commercial complementary metal-oxide semiconductor line. By respectively
      modulating the two modulation arms with a push-pull drive, a cross talk (CT) of
      less than -18 dB is obtained for the switching element with 150-MUm-long
      modulation arms. The total steady-state power consumption of the switch matrix
      ranges from 4.46 to 35.92 mW for different routing states. The CT values of the
      routing state with the minimum and maximum power consumptions are less than -19
      dB and less than -12 dB, respectively.

PMID- 24081091
TI  - Multicasting in a spatial division multiplexing system based on optical orbital
      angular momentum.
AB  - We report multicasting data from a single orbital angular momentum (OAM) spatial
      channel onto multiple OAM channels of equally spaced OAM charge numbers. The
      designed sliced phase patterns for multicasting are loaded on the spatial light
      modulator. By optimizing the design of the phase pattern, the power of
      multicasted OAM channels can be equalized. We experimentally demonstrate
      multicasting five and seven OAM channels from a single-input OAM channel carrying
      a 100  Gbit/s quadrature phase-shift keying (QPSK) data stream. 

PMID- 24081092
TI  - Three-dimensional nonparaxial beams in parabolic rotational coordinates.
AB  - We introduce a class of three-dimensional nonparaxial optical beams found in a
      parabolic rotational coordinate system. These beams, representing exact solutions
      of the nonparaxial Helmholtz equation, have inherent parabolic symmetries.
      Assisted with a computer-generated holography, we experimentally demonstrate the
      generation of different modes of these beams. The observed transverse beam
      patterns along the propagation direction agree well with those from our
      theoretical predication. 

PMID- 24081093
TI  - Sharper focal spot generated by 4pi tight focusing of higher-order Laguerre
      Gaussian radially polarized beam.
AB  - The focal electric fields for a 4pi high numerical aperture (NA) focusing system
      with both the doughnut and higher-order Laguerre-Gaussian (LG) radially polarized
      (RP) beams are investigated in the case of NA=1, and the full width at half
      maximum values of the focal spots are calculated. Compared with the single-lens
      high NA focusing configuration, a sharper spot, whose size is reduced efficiently
      in the transverse as well as the axial direction, can be formed. Such size
      reduction is attributed to not only the destruction interference of the
      longitudinal component caused by the pi phase shift between any two adjacent
      rings of the incident higher-order LG RP beam coming from one particular
      direction but also the perfect destruction interference of the radial component
      formed by the two counter-propagating incident beams. 

PMID- 24081094
TI  - High-quality optical vortex-beam generation by using a multilevel vortex
      producing lens.
AB  - In the present work, we propose a method to generate high-quality optical
      vortices with a reduced number of phase levels by using multilevel vortex
      producing lenses (VPLs). The VPL is implemented in a liquid-crystal spatial light
      modulator with limited capacity to project phase levels. The proposed method
      significantly improves the quality of the optical vortex obtained by employing
      spiral phase plates with the same number of phase levels. Simulations and
      experimental results confirming the effectiveness of the method are presented. 

PMID- 24081095
TI  - Optimizing 3D multiphoton fluorescence microscopy.
AB  - We present a new optimization concept for 3D multiphoton fluorescence microscopy
      by finding the optimal excitation beam giving rise to the smallest possible light
      emitting volume or the highest possible signal to noise ratio (SNR). 

PMID- 24081096
TI  - Lateral shifts and photon tunneling in a frustrated total internal reflection
      structure with a negative-zero-positive index metamaterial.
AB  - Motivated by the realization of the Dirac point (DP) with a double-cone structure
      for optical field in the negative-zero-positive index metamaterial (NZPIM), the
      lateral shift and tunneling time of photon tunneling through a frustrated total
      internal reflection structure containing a NZPIM barrier are investigated by
      employing Artman's stationary phase method. Near the DP, the lateral shift can
      vary from positive to negative and the photon tunneling displays a superluminal
      dynamic. Because of the Hartman effect, both lateral shift and tunneling time
      tend to a saturation value when the barrier thickness increases. These results
      may lead to potential applications in integral optics and optical-based devices
      and also suggest analogous phenomena of valance electron in single-layered carbon
      graphene. 

PMID- 24081097
TI  - Generation of parabolic similaritons in tapered silicon photonic wires:
      comparison of pulse dynamics at telecom and mid-infrared wavelengths.
AB  - We study the generation of parabolic self-similar optical pulses in tapered Si
      photonic nanowires (Si-PhNWs) at both telecom (lambda=1.55 MUm) and mid-infrared
      (lambda=2.2 MUm) wavelengths. Our computational study is based on a rigorous
      theoretical model, which fully describes the influence of linear and nonlinear
      optical effects on pulse propagation in Si-PhNWs with arbitrarily varying width.
      Numerical simulations demonstrate that, in the normal dispersion regime, optical
      pulses evolve naturally into parabolic pulses upon propagation in millimeter-long
      tapered Si-PhNWs, with the efficiency of this pulse-reshaping process being
      strongly dependent on the spectral and pulse parameter regime in which the device
      operates, as well as the particular shape of the Si-PhNWs.

PMID- 24081098
TI  - Resolving spatial modes of lasers via matrix completion.
AB  - We explain a technique that recovers the structure and the modal weights of
      spatial modes of lasers from a limited number of spatial coherence measurements.
      Our approach interpolates the unobserved spatial coherence measurements via the
      low-rank matrix completion algorithm based on nuclear norm minimization and then
      extracts the set of modes via singular value decomposition. Numerical examples
      are provided on a variety of lasers to demonstrate the effectiveness of the
      method, and it is shown that the proposed method can further reduce the number of
      measurements by a factor of 2 for a moderate data size. 

PMID- 24081099
TI  - Single-exposure surface profilometry using partitioned aperture wavefront
      imaging.
AB  - We demonstrate a technique for instantaneous measurements of surface topography
      based on the combination of a partitioned aperture wavefront imager with a lamp
      based reflection microscope using standard objectives. The technique can operate
      at video rate over large fields of view, and provides nanometer axial resolution
      and submicrometer lateral resolution. We discuss performance characteristics of
      this technique, which we experimentally compare with scanning white light
      interferometry. 

PMID- 24081100
TI  - AlGaAs microdisk cavities for second-harmonic generation.
AB  - We report on the design, the fabrication, and the optical characterization of
      AlGaAs microdisks suspended on a GaAs pedestal, conceived for second-harmonic
      generation with a pump in the third telecom window. We discuss the results
      concerning the linear characterization of whispering gallery modes at fundamental
      and second-harmonic wavelengths, an essential step prior to the investigation of
      quasi-phase-matched processes in this type of microcavity. 

PMID- 24081101
TI  - Spectroscopic ellipsometry on metal and metal-oxide multilayer hybrid plasmonic
      nanostructures.
AB  - The effective medium approximation is used to determine the optical constants of
      novel silver (Ag)/indium-tin oxide (ITO) multilayer nanopillar structures within
      the 300-800 nm wavelength range. The structures are modeled as inclusions in air
      with the pillar volume fraction at 42.4%, agreeing with SEM images of the sample.
      The simulated reflection intensity of the nanopillars is much less than that of
      the planar reference sample and is a result of the small difference between the
      refractive index of the top effective medium layer and that of air. Furthermore,
      the minimum in the reflection at around 450 nm in the nanostructured sample is
      evidence of surface plasmon enhancement, indicating suitability for plasmonic
      applications. The simulated Brewster angle decreases in the pillar region, which
      is an indication of smaller effective refractive index. 

PMID- 24081102
TI  - Enhanced optical absorption in nanohole-textured silicon thin-film solar cells
      with rear-located metal particles.
AB  - We report the computational modeling of Ag nanoparticles deposited on the rear of
      a nanohole-textured silicon thin film to achieve higher absorption for silicon
      solar cells. The silicon nanoholes and the rear-located Ag nanoparticles can
      enhance the absorption in the silicon thin film. The short circuit current
      density for nanohole-textured silicon thin film can be further improved by about
      11.6% by Ag nanoparticles. The combination of silicon nanoholes and plasmonic
      metal nanoparticles provides a promising way to enhance the absorption of silicon
      thin-film solar cells. 

PMID- 24081103
TI  - Active wide-field illumination for high-throughput fluorescence lifetime imaging.
AB  - Wide-field fluorescence lifetime imaging allows for fast imaging of large sample
      areas at the cost of low sensitivity to weak fluorescence signals. To overcome
      this challenge, we developed an active wide-field illumination (AWFI) strategy to
      optimize the impinging spatial intensity for acquiring optimal fluorescence
      signals over the whole sample. We demonstrated the ability of AWFI to accurately
      estimate lifetimes from a multiwell plate sample with concentrations ranging over
      two orders of magnitude. We further reported its successful application to a
      quantitative Forster resonance energy transfer lifetime cell-based assay.
      Overall, this method allows for enhanced accuracy in lifetime-based imaging at
      high acquisition speed over samples with large fluorescence intensity
      distributions. 

PMID- 24081104
TI  - Determinants of reactivation of inapparent Strongyloides stercoralis infection in
      patients hospitalized for unrelated admitting diagnosis.
AB  - BACKGROUND: Clinical presentation of strongyloidiasis in humans is highly
      variable, ranging from clinically inapparent infection to life-threatening
      multisystem disease. The course of infection is dependent on the immune status of
      the patient. Our objective was to ascertain the clinical characteristics of
      patients who developed reactivated strongyloidiasis from a primary infection
      acquired in the past, and to evaluate risk factors that contributed to its
      exacerbation. METHODS: We identified 31 patients diagnosed with strongyloidiasis
      by stool examination at our institution from January 2007 to June 2012. We
      reviewed their clinical records and selected eight patients whose admitting
      diagnosis was not suggestive of strongyloidiasis-associated gastrointestinal
      disease. However, they developed symptoms consistent with strongyloidiasis during
      their hospitalization, and stool examinations revealed diagnostic larvae. RESULTS
      AND CONCLUSION: We have identified immunosuppressive therapy, viral infection
      associated immunodeficiency, alcoholism, and diabetes mellitus as risk factors
      for reactivation of chronic inapparent strongyloidiasis. Analysis of hemogram
      data suggests the low sensitivity of hypereosinophilia to be a marker for this
      helminthiasis.

PMID- 24081105
TI  - Symptoms associated with finding colorectal cancer during colonoscopy.
AB  - BACKGROUND: Patients with an increased risk of having colorectal cancer (CRC)
      should have priority on the colonoscopy list. OBJECTIVE: To investigate whether
      presenting symptoms of patients referred for colonoscopy could help in
      identifying patients with an increased risk of CRC. PATIENTS AND METHODS: Between
      February 2007 and November 2010, random outpatients referred for colonoscopy were
      asked to fill out a questionnaire with respect to symptoms for which the
      colonoscopy was performed. Informed consent was obtained to review the
      colonoscopy and histology reports. Multivariate logistic regression was performed
      to identify predictors for CRC. RESULTS: In total, 1458 (21%) patients returned
      the questionnaire, of whom 925 (63.4%) had undergone previous sigmoidoscopy or
      colonoscopy. CRC was detected in 41 patients (2.8%). Age over 50 years [adjusted
      odds ratio (aOR) 3.00; 95% confidence interval (CI) 1.30-6.91] and presenting
      symptoms of rectal blood loss (aOR 4.62; 95% CI 2.31-9.22) and a change in bowel
      habits (aOR 3.33; 95% CI 1.50-7.40) were associated independently with an
      increased risk of finding CRC. Previous sigmoidoscopy or colonoscopy (aOR 0.24;
      95% CI 0.12-0.49) and fatigue as presenting symptoms (aOR 0.22; 95% CI 0.09-0.56)
      were associated with a decreased risk of CRC. Weight loss, self-reported anemia,
      and abdominal pain were not associated with CRC in this study. CONCLUSION:
      Patients presenting with rectal blood loss, change in bowel habits, and those
      older than 50 years of age have an increased risk of a finding of CRC during
      colonoscopy. We recommend that these risk groups should be prioritized on the
      colonoscopy list over patients who have undergone a previous endoscopy or who are
      presenting with fatigue.

PMID- 24081106
TI  - Epidemiological aspects of biliary tree tumors in a region of northern Italy:
      emerging trends and sex-based differences.
AB  - BACKGROUND: Cholangiocarcinoma (CCA) and gallbladder cancer are the second cause
      of liver malignancy after hepatocellular carcinoma. Epidemiological data point to
      an increase in the incidence of CCA in both western and eastern countries;
      however, data on more recent years are lacking. AIMS: The aim of this study was
      to elucidate the more recent epidemiology of CCA and gallbladder carcinoma in
      north-east Italy using automatically collected regional data on hospital
      admissions over a 10-year period. MATERIALS AND METHODS: We performed a
      retrospective analysis of the Veneto region (north-east Italy) database of
      patients' hospital discharge records, identifying cases with the following codes:
      intrahepatic cholangiocarcinoma (155.1), primary gallbladder cancer (156.0), and
      primary extrahepatic biliary tract cancer (156.1). Hospitalizations were recorded
      according to the surgical or medical procedures involved (based on International
      Classification of Diseases-9 procedure codes), and only the first hospitalization
      was considered for the 2005-2009 period. RESULTS: The number of hospitalizations
      for biliary tumors as a whole has remained stable over the past 10 years. The
      hospitalization rate of intrahepatic CCA is increasing; this cancer is more
      frequent in males than in females. The hospitalization rate for gallbladder
      cancer is increasing with age. However, the figures for extrahepatic CCA have
      remained stable over the past 10 years. The duration of survival was
      significantly longer for patients who underwent radical surgery than for those
      who did not. CONCLUSION: Efforts are needed to prevent CCA, bearing in mind the
      emerging conditions associated with its onset. Secondary prevention of these
      tumors will substantially improve the duration of survival.

PMID- 24081108
TI  - Sulfur-assisted domino access to bicyclic dihydrofurans: case study and early
      synthetic applications.
AB  - A DDQ-mediated domino reaction (up to six steps in a single process) has been
      developed to selectively provide substituted dihydrofurans from a common starting
      material containing a cyclic bis-thioenol ether. Study of the reaction mechanism
      highlighted a role played by the sulfur-containing moiety in influencing reaction
      rate and stereoselectivity. 

PMID- 24081107
TI  - Detection of anticonductive tissue autoantibodies in a patient with chronic
      intestinal pseudo-obstruction and sick sinus syndrome.
AB  - A 26-year-old patient was diagnosed as having chronic intestinal pseudo
      obstruction with manometric and histopathologic features suggestive of an
      intestinal myopathy. Histology was characterized by smooth muscle degeneration
      without inflammatory or immune cells. The severe gut dysfunction required full
      parenteral nutritional support. After a few months, the patient developed
      symptomatic tachy-brady arrhythmia episodes with syncopes. A thorough diagnostic
      work-up led to a diagnosis of sick sinus syndrome, which was managed by pacemaker
      implantation and administration of beta-blockers. This led to a partial
      improvement in tachy-brady arrhythmia episodes. Nonetheless, the patient
      continued to experience sustained supraventricular tachyarrhythmia runs, poorly
      responsive to increasing beta-blocker doses. To investigate the origin of the
      cardiologic impairment, the patient was tested for anticonductive tissue
      autoantibodies, which were positive, thus supporting a possible autoimmune origin
      of the dysrhythmia. Other autoantibodies were negative. On the basis of these
      findings, the patient was treated with high-dose steroids, which were then
      tapered. The patient responded to the steroid treatment and did not experience
      further episodes of syncope and tachyarrhythmias. The severe gut dysfunction
      remained unchanged. This case highlights an association between severe gut
      dysfunction and cardiac conductive tissue abnormalities, with autoantibodies to
      conductive tissue possibly causing the dysrhythmia. The severe gut and heart
      (likely autoimmune-mediated) dysfunction presented in this case provides a basis
      to further assess a link between intestinal and cardiac abnormal rhythmicity. 

PMID- 24081109
TI  - Gennady A. Buznikov, PhD (1931-2012): father of neurotransmitters as
      developmental signals.

PMID- 24081110
TI  - Medical malpractice in the outpatient setting: through a glass, darkly.

PMID- 24081111
TI  - High frequency of varicella zoster virus reactivation associated with the use of
      arsenic trioxide in patients with acute promyelocytic leukemia.

PMID- 24081112
TI  - Models of short bowel syndrome in pigs: a technical review.
AB  - BACKGROUND: Short bowel syndrome (SBS) is still a life-threatening disease in
      both children and adults. Although the therapeutic options are improving,
      challenges still remain, and to overcome these challenges is a major focus of SBS
      research today. In order to simulate anatomical and physiological conditions
      similar to those in humans for research, porcine models of SBS are often used.
      Various approaches for generating SBS models have been described in the
      literature. METHODS/RESULTS: In this work, we present a review of different types
      of porcine models of SBS and outline the differences between those models
      regarding types of animals, surgical procedures, monitoring, and methods of
      assessment. CONCLUSION: The aim of this study was to select the most suitable SBS
      model regarding the purpose of the research.

PMID- 24081113
TI  - Overexpression of hypoxia-inducible factor-1alpha exacerbates endothelial barrier
      dysfunction induced by hypoxia.
AB  - BACKGROUND/AIMS: The mechanisms involved in endothelial barrier dysfunction
      induced by hypoxia are incompletely understood. There is debate about the role of
      hypoxia-inducible factor-1alpha (HIF-1alpha) in endothelial barrier disruption.
      The aim of this study was to investigate the effect of genetic overexpression of
      HIF-1alpha on barrier function and the underlying mechanisms in hypoxic
      endothelial cells. METHODS: The plasmid pcDNA3.1/V5-His-HIF-1alpha was stably
      transfected into human endothelial cells. The cells were exposed to normoxia or
      hypoxia. The mRNA and protein expressions of HIF-1alpha were detected by RT-PCR
      and Western blot respectively. The barrier function was assessed by measuring the
      transendothelial electrical resistance (TER). The Western blot analysis was used
      to determine the protein expression of glucose transporter-1 (GLUT-1), zonular
      occludens-1 (ZO-1), occludin, and myosin light chain kinase (MLCK) in endothelial
      cells. The mRNA expression of proinflammatory cytokines was detected by qRT-PCR.
      RESULTS: Genetic overexpression of HIF-1alpha significantly increased the mRNA
      and protein expression of HIF-1alpha in endothelial cells. The overexpression of
      HIF-1alpha enhanced the hypoxia-induced increase of HIF-1alpha and GLUT-1 protein
      expression. HIF-1alpha overexpression not only exacerbated hypoxia-induced
      endothelial barrier dysfunction but also augmented hypoxia-induced up-regulation
      of MLCK protein expression. HIF-1alpha overexpression also enhanced IL-1beta, IL
      6 and TNF-alpha mRNA expression. CONCLUSION: We provide evidence that genetic
      overexpression of HIF-1alpha aggravates the hypoxia-induced endothelial barrier
      dysfunction via enhancing the up-regulation of MLCK protein expression caused by
      hypoxia, suggesting a potential role for HIF-1alpha in the pathogenesis of
      endothelial barrier dysfunction in hypoxia.

PMID- 24081115
TI  - Racial-ethnic variation in U.S. mental health service use among Latino and Asian
      non-U.S. citizens.
AB  - OBJECTIVE: This study examined the factors associated with service utilization
      for mental health conditions among Latino and Asian non-U.S. citizens in the
      United States by service type and race. METHODS: Data were obtained from the
      National Latino and Asian American Study (NLAAS). The sample for this study was
      849 Latino and 595 Asian non-U.S. citizens between ages 18 and 64 (N=1,444).
      Mental health services obtained through three types of service providers were
      examined: specialty mental health services, general medical services, and other
      services. Guided by the modified Andersen health behavioral model, analyses
      involved logistic regression models conducted with penalized maximum likelihood
      estimation. RESULTS: Although having a psychiatric disorder increased mental
      health service use in both groups, only 32% of Latino and 52% of Asian non-U.S.
      citizens with psychiatric needs reported using mental health services during the
      past 12 months. Overall, noncitizen Latinos and Asians were more likely to use
      mental health services from general health care providers and other providers
      than from specialty mental health providers. Several significant predisposing,
      enabling, and need factors, such as age, health insurance, and having psychiatric
      conditions, also interacted with race. CONCLUSIONS: Findings of the study suggest
      that there are ethnoracial variations in mental health service use between Latino
      and Asian non-U.S. citizens. Mental health professionals should consider
      developing tailored mental health interventions that account for cultural
      variations to enhance access to services for these vulnerable subgroups of
      Latinos and Asians. Further research should examine ethnic disparities in mental
      health service use among various non-U.S. citizen racial-ethnic subgroups.

PMID- 24081114
TI  - Things change: how comparative transcriptomics suggest the pallium has evolved at
      multiple levels of organization.

PMID- 24081116
TI  - Innervation zone of the vastus medialis muscle: position and effect on surface
      EMG variables.
AB  - The aim of this study was to investigate the position of the innervation zone
      (IZ) of the vastus medialis (VM) and its effect on the electromyographic (EMG)
      amplitude and mean frequency estimates. Eighteen healthy subjects performed
      maximal isometric knee extensions at three knee angles. Surface EMG signals were
      collected by using a 16 * 8 electrode grid placed on the VM muscle. The position
      of the IZ was estimated through visual analysis, and traditional bipolar signals
      were obtained from channels over and away from it; amplitude and mean frequency
      values were extracted and compared using an analysis of variance (ANOVA) with
      repeated measures. The IZ is shaped as a line running from the proximal-lateral
      to the distal-medial aspect of the VM muscle. The presence of an IZ under the
      electrodes lowered the EMG amplitude (P < 0.001, F = 58.11) and increased the EMG
      mean frequency (P < 0.001, F = 26.47); variations of these parameters due to the
      knee flexion angle were less frequently observed in EMG signals collected over
      than away from the IZ. Electrodes placed 'over the belly of the VM muscle' are
      likely to collect EMG signals influenced by the presence of the IZ, thus
      hindering the detection of changes in muscle activity. 

PMID- 24081117
TI  - Sonia Skarlatos: a colleague and a shepherd of gene therapy.

PMID- 24081120
TI  - On the mechanism and benefit of siRNA-mediated targeting of CD47 in cancer.

PMID- 24081121
TI  - Reply to "On the mechanism and benefit of siRNA-mediated targeting of CD47 in
      cancer".

PMID- 24081122
TI  - Panorama from the oncolytic virotherapy summit.

PMID- 24081123
TI  - TALENs targeting HBV: designer endonuclease therapies for viral infections.

PMID- 24081124
TI  - Removing the immune response from muscular dystrophy research.

PMID- 24081126
TI  - Self-care, health models, and an international home care nurses organization
      update.

PMID- 24081128
TI  - Perceived value of a urinary catheter self-management program in the home.
AB  - A long-term indwelling urinary catheter intervention was tested in a randomized
      trial that is described in this article. The perceived value of the intervention
      to the catheter users, one of the study's specific aims, was assessed at the end
      of their 12-month participation and is reported here. Study participants'
      responses, our findings, and implications for home healthcare are discussed. 

PMID- 24081129
TI  - The impact of nursing students' use of electronic health records in the home
      setting.
AB  - The purpose of this study was to explore the perceptions of senior undergraduate
      nursing students and perceptions of home care clients regarding the use of a new
      electronic health record and its impact on client care and communication.
      Findings indicate that providing students with the opportunity and time to become
      familiar with the use of computers during client care in the educational
      environment allows them to move more comfortably from a computer-focused visit to
      client-focused nursing care. 

PMID- 24081130
TI  - Collaborations between home healthcare agencies and schools of nursing: bridging
      the theory-practice gap at home.
AB  - Home healthcare (HHC) agencies and schools of nursing (SONs) share the mutual
      goal of using evidence-based knowledge to deliver care while fostering a
      professionally stimulating environment. As HHC agencies strive to deliver
      clinically effective, cost-efficient, patient-centered nursing care, SONs use
      scholarly methods to develop sound practitioners with investigative skills.
      Collaborations have long existed between these two entities, but few studies
      describe how theory and practice meld in the ever-growing HHC arena. The purpose
      of this article is to highlight the need for such future collaborations and to
      summarize some of the successful collaborative methods used by schools and
      agencies. Additionally, the collaboration between one nonprofit HHC agency and a
      university-based SON is described along with the challenges and benefits to both
      partners. 

PMID- 24081131
TI  - Getting on with living life: experiences of older adults after home care.
AB  - Providers in all settings are increasingly aware of the need to focus on
      transitional care needs and services across healthcare settings to improve
      quality of life, maintain optimal health, and prevent unnecessary
      hospitalizations. Home care is an essential piece of the transitional care
      puzzle, especially in providing services to support older adults with chronic
      comorbid conditions to remain at home safely with optimal health and psychosocial
      well-being. Home care is essential in bridging the gap from acute hospital care
      to home; however, little is known about the needs of older adults after discharge
      from home care. Our study investigated the perceptions of older adults with
      chronic health conditions after discharge from home care regarding their daily
      activities and healthcare needs and identified how these needs were met. 

PMID- 24081133
TI  - Using SBAR communications in efforts to prevent patient rehospitalizations.
AB  - Situation-Background-Assessment-Recommendation (SBAR) communication has become
      the standard for communicating across disciplines. It has demonstrated its
      effectiveness at improving patient outcomes, enhancing patient and clinician
      satisfaction, and helping to control healthcare costs. It can help home
      healthcare clinicians with efforts to prevent avoidable hospitalizations. But how
      often and how well do home health clinicians use this method of shared
      communications with physicians? This article explores why communication between
      physicians and home health clinicians can be so problematic. It introduces the
      SBAR communication method, its origins, its features, and some of the published
      evidence that it provides effective and efficient communication, thereby
      promoting better patient outcomes. 

PMID- 24081135
TI  - Medication appropriateness at end of life: a new tool for balancing medicine and
      communication for optimal outcomes--the BUILD model.
AB  - The BUILD model was created to provide a systematic framework for hospice
      clinicians to have important conversations with patients and families as well as
      facilitating useful conversations with interdisciplinary teammates. Although this
      article focuses on medication appropriateness and discontinuation of medications,
      this model can also be used when discussing prognosis, code status, goals of
      care, drug diversion, and when collaborating to develop a plan of care. When
      provided with a communication tool that is versatile, logical, and effective,
      hospice clinicians may use it, supporting improved patient care outcomes. 

PMID- 24081137
TI  - Partnerships in home care--one agency's journey with accountable care
      organizations.

PMID- 24081138
TI  - Advancing Care Excellence for Seniors: what is it?

PMID- 24081139
TI  - Genotype in the diagnosis of 21-hydroxylase deficiency: who should undergo
      CYP21A2 analysis?
AB  - AIMS: to confirm the diagnosis of 21-hydroxylase deficiency (21-OHD) by the
      analysis of CYP21A2 gene in infants with clinical and/or biochemical features of
      21-OHD in order to clarify which patients to submit to genetic analysis; to
      analyze the genotype-phenotype concordance in these infants. SUBJECTS AND
      METHODS: We studied 25 children with clinical and/or biochemical features of 21
      OHD. All of them and their parents were submitted to genetic analysis of CYP21A2.
      Patients were classified in 3 groups according to mutations' severity: severe
      (group A), moderate (group B) or mild (group C). RESULTS: CYP21A2 gene mutations
      were found in 17 children. Whereas all infants of groups A and B presented a
      classical form of 21- OHD, children of group C had a non-classical form of 21
      OHD. Four infants resulted heterozygotes and 4 children were wildtype. A girl
      clinically presenting a non-classical form of 21-OHD resulted compound
      heterozygote with one of the mutations not described in literature (R25W) and
      whose residual enzymatic activity is not already known. All affected children
      presented a 17-OHP level after ACTH stimulation greater than 100 nmol/l. We found
      an optimal concordance between 17-OHP levels after ACTH test and genotype.
      CONCLUSIONS: CYP21A2 analysis permitted to confirm the diagnosis of 21-OHD in 68%
      of our children. To improve this percentage we suggest to perform the CYP21A2
      analysis only when 17-OHP after ACTH test is greater than 100 nmol/l. Moreover,
      we found an optimal genotype-phenotype concordance in the 21-OHD patients.

PMID- 24081140
TI  - Tandem catalysis: a new approach to polymers.
AB  - The creation of polymers by tandem catalysis represents an exciting frontier in
      materials science. Tandem catalysis is one of the strategies used by Nature for
      building macromolecules. Living organisms generally synthesize macromolecules by
      in vivo enzyme-catalyzed chain growth polymerization reactions using activated
      monomers that have been formed within cells during complex metabolic processes.
      However, these biological processes rely on highly complex biocatalysts, thus
      limiting their industrial applications. In order to obtain polymers by tandem
      catalysis, homogeneous and enzyme catalysts have played a leading role in the
      last two decades. In the following feature article, we will describe selected
      published efforts to achieve these research goals. 

PMID- 24081141
TI  - Sphingosine kinases are not required for inflammatory responses in macrophages.
AB  - Sphingosine kinases (Sphks), which catalyze the formation of sphingosine 1
      phosphate (S1P) from sphingosine, have been implicated as essential intracellular
      messengers in inflammatory responses. Specifically, intracellular Sphk1-derived
      S1P was reported to be required for NFkappaB induction during inflammatory
      cytokine action. To examine the role of intracellular S1P in the inflammatory
      response of innate immune cells, we derived murine macrophages that lack both
      Sphk1 and Sphk2 (MPhi Sphk dKO). Compared with WT counterparts, MPhi Sphk dKO
      cells showed marked suppression of intracellular S1P levels whereas sphingosine
      and ceramide levels were strongly up-regulated. Cellular proliferation and
      apoptosis were similar in MPhi Sphk dKO cells compared with WT counterparts.
      Treatment of WT and MPhi Sphk dKO with inflammatory mediators TNFalpha or
      Escherichia coli LPS resulted in similar NFkappaB activation and cytokine
      expression. Furthermore, LPS-induced inflammatory responses, mortality, and
      thioglycolate-induced macrophage recruitment to the peritoneum were
      indistinguishable between MPhi Sphk dKO and littermate control mice.
      Interestingly, autophagic markers were constitutively induced in bone marrow
      derived macrophages from Sphk dKO mice. Treatment with exogenous sphingosine
      further enhanced intracellular sphingolipid levels and autophagosomes. Inhibition
      of autophagy resulted in caspase-dependent cell death. Together, these data
      suggest that attenuation of Sphk activity, particularly Sphk2, leads to increased
      intracellular sphingolipids and autophagy in macrophages. 

PMID- 24081142
TI  - Targeted inhibition of phospholipase C gamma2 adaptor function blocks
      osteoclastogenesis and protects from pathological osteolysis.
AB  - Phospholipase C gamma2 (PLCgamma2) is a critical regulator of innate immune cells
      and osteoclasts (OCs) during inflammatory arthritis. Both the catalytic domain
      and the adaptor motifs of PLCgamma2 are required for OC formation and function.
      Due to the high homology between the catalytic domains of PLCgamma2 and the
      ubiquitously expressed PLCgamma1, molecules encompassing the adaptor motifs of
      PLCgamma2 were designed to test the hypothesis that uncoupling the adaptor and
      catalytic functions of PLCgamma2 could specifically inhibit osteoclastogenesis
      and bone erosion. Wild-type (WT) bone marrow macrophages (BMM) that overexpress
      the tandem Src homology 2 (SH2) domains of PLCgamma2 (SH2(N+C)) failed to form
      mature OCs and resorb bone in vitro. Activation of the receptor activator of NF
      kappaB (RANK) signaling pathway, which is critical for OC development, was
      impaired in cells expressing SH2(N+C). Arrest in OC differentiation was evidenced
      by a reduction of p38 and Ikappa-Balpha phosphorylation as well as decreased
      NFATc1 and c-Fos/c-Jun levels. Consistent with our hypothesis, SH2(N+C) abrogated
      formation of the RANK-Gab2 complex, which mediates NF-kappaB and AP-1 activation
      following RANK ligand (RANKL) stimulation. Furthermore, the ability of SH2(N+C)
      to prevent inflammatory osteolysis was examined in vivo following RANKL or LPS
      injections over the calvaria. Both models induced osteolysis in the control
      group, whereas the SH2(N+C)-treated cohort was largely protected from bone
      erosion. Collectively, these data indicate that inflammatory osteolysis can be
      abrogated by treatment with a molecule composed of the tandem SH2 domains of
      PLCgamma2. 

PMID- 24081143
TI  - Methamphetamine-induced occludin endocytosis is mediated by the Arp2/3 complex
      regulated actin rearrangement.
AB  - Methamphetamine (METH) is a drug of abuse with neurotoxic and neuroinflammatory
      effects, which include disruption of the blood-brain barrier (BBB) and
      alterations of tight junction protein expression. This study focused on the actin
      cytoskeletal rearrangement as a modulator of METH-induced redistribution of tight
      junction protein occludin in brain endothelial cells. Exposure to METH resulted
      in a shift of occludin localization from plasma membranes to endosomes. These
      changes were accompanied by activation of the actin-related protein 2/3 (Arp2/3)
      complex, which stimulates actin polymerization by promoting actin nucleation. In
      addition, METH-induced coronin-1b phosphorylation diminishes the inhibitory
      effect of nonphosphorylated coronin-1b on actin nucleation. Blocking actin
      nucleation with CK-666, a specific inhibitor of the Arp2/3 complex, protected
      against METH-induced occludin internalization and increased transendothelial
      monocyte migration. Importantly, treatment with CK-666 attenuated a decrease in
      occludin levels in brain microvessels and BBB permeability of METH-injected mice.
      These findings indicate that actin cytoskeletal dynamics is detrimental to METH
      induced BBB dysfunction by increasing internalization of occludin. 

PMID- 24081144
TI  - Allelic interference: a mechanism for trans-dominant transmission of loss of
      function in the neurodegeneration of familial Alzheimer's disease.
AB  - Presenilins (PSs) are catalytic components of the gamma-secretase complexes that
      promote the epsilon-cleavage of cell surface proteins producing cytosolic
      peptides shown to function in cell signaling and gene expression. In addition,
      secretase cleavages at gamma-sites of amyloid precursor protein substrates
      produce the amyloid-beta (Abeta) peptides found in all people. Aggregation of
      Abeta peptides form the amyloid fibrils found in amyloid plaques of Alzheimer's
      disease (AD) patients and aged individuals. A common hypothesis suggests that AD
      is caused by aggregated Abeta peptides, but treatments with either inhibitors of
      Abeta production or anti-Abeta antibodies showed no therapeutic value.
      Importantly, recent evidence [Marambaud et al.: Cell 2003;114:635-645] shows that
      PS familial AD (FAD) mutations cause a loss of gamma-secretase cleavage function
      at the epsilon-site of substrates manifested by a decreased production of
      cytosolic peptides and an accumulation of transmembrane gamma-secretase
      substrates. These data support the hypothesis that PS FAD mutations promote
      neurotoxicity by inhibiting the gamma-secretase-catalyzed epsilon-cleavage of
      substrates, thus reducing cell signaling while causing accumulation of membrane
      bound cytotoxic peptides. Similar mechanisms may be involved in toxicities
      observed in clinical trials of gamma-secretase inhibitors. A model of allelic
      interference may explain the dominant negative transmission of neurotoxic loss of
      function in FAD neurodegeneration.

PMID- 24081145
TI  - Primary care closed claims experience of Massachusetts malpractice insurers.
AB  - IMPORTANCE: Despite prior focus on high-impact inpatient cases, there are
      increasing data and awareness that malpractice in the outpatient setting,
      particularly in primary care, is a leading contributor to malpractice risk and
      claims. OBJECTIVE: To study patterns of primary care malpractice types, causes,
      and outcomes as part of a Massachusetts ambulatory malpractice risk and safety
      improvement project. DESIGN, SETTING, AND PARTICIPANTS: Retrospective review of
      pooled closed claims data of 2 malpractice carriers covering most Massachusetts
      physicians during a 5-year period (January 1, 2005, through December 31, 2009).
      Data were harmonized between the 2 insurers using a standardized taxonomy.
      Primary care practices in Massachusetts. All malpractice claims that involved
      primary care practices insured by the 2 largest insurers in the state were
      screened. A total of 551 claims from primary care practices were identified for
      the analysis. MAIN OUTCOMES AND MEASURES: Numbers and types of claims, including
      whether claims involved primary care physicians or practices; classification of
      alleged malpractice (eg, misdiagnosis or medication error); patient diagnosis;
      breakdown in care process; and claim outcome (dismissed, settled, verdict for
      plaintiff, or verdict for defendant). RESULTS: During a 5-year period there were
      7224 malpractice claims of which 551 (7.7%) were from primary care practices.
      Allegations were related to diagnosis in 397 (72.1%), medications in 68 (12.3%),
      other medical treatment in 41 (7.4%), communication in 15 (2.7%), patient rights
      in 11 (2.0%), and patient safety or security in 8 (1.5%). Leading diagnoses were
      cancer (n = 190), heart diseases (n = 43), blood vessel diseases (n = 27),
      infections (n = 22), and stroke (n = 16). Primary care cases were significantly
      more likely to be settled (35.2% vs 20.5%) or result in a verdict for the
      plaintiff (1.6% vs 0.9%) compared with non-general medical malpractice claims (P
      < .001). CONCLUSIONS AND RELEVANCE: In Massachusetts, most primary care claims
      filed are related to alleged misdiagnosis. Compared with malpractice allegations
      in other settings, primary care ambulatory claims appear to be more difficult to
      defend, with more cases settled or resulting in a verdict for the plaintiff.

PMID- 24081146
TI  - Mutations in GERANYLGERANYL DIPHOSPHATE SYNTHASE 1 affect chloroplast development
      in Arabidopsis thaliana (Brassicaceae).
AB  - PREMISE OF THE STUDY: Within plastids, geranylgeranyl diphosphate synthase is a
      key enzyme in the isoprenoid biosynthetic pathway that catalyzes the formation of
      geranylgeranyl diphosphate, a precursor molecule to several biochemical pathways
      including those that lead into the biosynthesis of carotenoids and abscisic acid,
      prenyllipids such as the chlorophylls, and diterpenes such as gibberellic acid. *
      METHODS: We have identified mutants in the GERANYLGERANYL DIPHOSPHATE SYNTHASE 1
      (GGPS1) gene, which encodes the major plastid-localized enzyme geranylgeranyl
      diphosphate synthase in Arabidopsis thaliana. * KEY RESULTS: Two T-DNA insertion
      mutant alleles (ggps1-2 and ggps1-3) were found to result in seedling-lethal
      albino and embryo-lethal phenotypes, respectively, indicating that GGPS1 is an
      essential gene. We also identified a temperature-sensitive leaf variegation
      mutant (ggps1-1) in A. thaliana that is caused by a point mutation. Total
      chlorophyll and carotenoid levels were reduced in ggps1-1 white tissues as
      compared with green tissues. Phenotypes typically associated with a reduction in
      gibberellic acid were not seen, suggesting that gibberellic acid biosynthesis is
      not noticeably altered in the mutant. In contrast to other variegated mutants,
      the ggps1-1 green sector photosynthetic rate was not elevated relative to wild
      type tissues. Chloroplast development in green sectors of variegated leaves
      appeared normal, whereas cells in white sectors contained abnormal plastids with
      numerous electron translucent bodies and poorly developed internal membranes. *
      CONCLUSIONS: Our results indicate that GGPS1 is a key gene in the chlorophyll
      biosynthetic pathway.

PMID- 24081147
TI  - Cone thermogenesis and its limits in the tropical Cycas micronesica (Cycadaceae):
      association with cone growth, dehiscence, and post-dehiscence phases.
AB  - PREMISE OF THE STUDY: Thermogenesis is a prominent pollination-related feature
      of cycad cones and is generally assumed to play a role in pollination. Although
      typically studied just before, during, and immediately after the cones'
      pollination phase, thermogenesis may be present in other cone developmental
      phases. * METHODS: We assayed thermogenesis in Cycas micronesica, Guam's
      endangered cycad, over successive cone developmental phases by measuring
      temperatures in shaded and unshaded in situ cones for up to 7 wk. We also studied
      the effect of ambient conditions on cone thermogenesis in laboratory experiments
      and estimated the cones' metabolic heating rates. * KEY RESULTS: Pollen cones
      exhibit a continuous, but small, metabolically generated thermogenesis for
      multiple weeks, including a single thermogenic peak temperature greater than peak
      ambient each day. The magnitudes of those daily peak temperature elevations above
      ambient reach maxima twice during cone development: a few days before dehiscence
      and approximately 1 wk post-dehiscence. Excised cones in dark, fixed temperature
      environments generated multiple thermogenic events (~24 h period) over ~10 d.
      Cones appear to initiate a protective temperature regulatory response at
      temperatures >=~38 degrees C. * CONCLUSIONS: Cycas micronesica pollen cones
      exhibit several thermogenic attributes not reported in other cycads, including
      continuous thermogenesis for many weeks. These cones grow in a hot tropical
      environment that likely confines their metabolically generated temperature
      increases to a small thermogenic window beyond which they encounter heat stress.
      These findings suggest the presence of thermogenic functions not strictly related
      to pollination and a potential vulnerability to warming climates.

PMID- 24081148
TI  - Abstracts of the European Vitreoretinal Update 2013, the 13th Euretina Congress.
      September 2013. Hamburg, Germany.

PMID- 24081149
TI  - Synthesis and structural characterization of the individual diastereoisomers of a
      cross-stapled alkene-bridged nisin DE-ring mimic.
AB  - Herein, we describe the synthesis, structural characterization, and synthetic use
      as an advanced intermediate of a cross-stapled alkene-bridged hexapeptide to
      mimic the DE-ring of the lantibiotic nisin. The linear precursor was cyclized by
      ring-closing metathesis to give the correctly folded bicyclic hexapeptide in a
      single step, and the four individual diastereoisomers were isolated, structurally
      assigned and characterized by HPLC, NMR and MS, respectively. The bicyclic
      hexapeptide was used as a versatile advanced synthon and was modified at its C-
      and N-terminus, among others, with an azide moiety to access a building block
      suitable for Cu(I)-catalyzed alkyne-azide cycloaddition-based ligation reactions.

PMID- 24081150
TI  - Abstracts of the 6th European Congress for Integrative Medicine (ECIM) together
      with the 5th German Congress for Integrative Medicine. October 4-5, 2013. Berlin,
      Germany.

PMID- 24081151
TI  - Systemic mastocytosis accompanied by a non-secretory plasma cell dyscrasia and
      nephrotic syndrome-level proteinuria in a 76-year-old patient.
AB  - We report here the interesting case of a 76-year-old man with severe proteinuria
      who was diagnosed with systemic mastocytosis accompanied by a clonal non-mast
      cell lineage haematological disorder (a non-secretory plasma cell dyscrasia).
      This is a unique report of systemic mastocytosis with a non-secretory plasma cell
      dyscrasia and nephrotic syndrome. The pathophysiological relevance between these
      entities along with the probability of occult amyloidosis is discussed. 

PMID- 24081152
TI  - Planning for a rare clinical challenge--simulating a sextuplet delivery.

PMID- 24081153
TI  - Increases in intracellular pH facilitate endocytosis and decrease availability of
      voltage-gated proton channels in osteoclasts and microglia.
AB  - Voltage-gated proton channels (H(+) channels) are highly proton-selective
      transmembrane pathways. Although the primary determinants for activation are the
      pH and voltage gradients across the membrane, the current amplitudes fluctuate
      often when these gradients are constant. The aim of this study was to investigate
      the role of the intracellular pH (pHi) in regulating the availability of H(+)
      channels in osteoclasts and microglia. In whole-cell clamp recordings, the pHi
      was elevated after exposure to NH4Cl and returned to the control level after
      washout. However, the H(+) channel conductance did not recover fully when the
      exposure was prolonged (>5 min). Similar results were observed in osteoclasts and
      microglia, but not in COS7 cells expressing a murine H(+) channel gene (mVSOP).
      As other electrophysiological properties, like the gating kinetics and voltage
      dependence for activation, were unchanged, the decreases in the H(+) channel
      conductance were probably due to the decreases in H(+) channels available at the
      plasma membrane. The decreases in the H(+) channel conductances were accompanied
      by reductions in the cell capacitance. Exposure to NH4Cl increased the uptake of
      the endocytosis marker FM1-43, substantiating the idea that pHi increases
      facilitated endocytosis. In osteoclasts, whose plasma membrane expresses V
      ATPases and H(+) channels, pHi increases by these H(+)-transferring molecules in
      part facilitated endocytosis. The endocytosis and decreases in the H(+) channel
      conductance were reduced by dynasore, a dynamin blocker. These results suggest
      that pHi increases in osteoclasts and microglia decrease the numbers of H(+)
      channels available at the plasma membrane through facilitation of dynamin
      dependent endocytosis.

PMID- 24081154
TI  - Submaximal ADP-stimulated respiration is impaired in ZDF rats and recovered by
      resveratrol.
AB  - Mitochondrial dysfunction and reactive oxygen species (ROS) have been implicated
      in the aetiology of skeletal muscle insulin resistance, although there is
      considerable controversy regarding these concepts. Mitochondrial function has
      been traditionally assessed in the presence of saturating ADP, but ATP turnover
      and the resultant ADP is thought to limit respiration in vivo. Therefore, we
      investigated the potential link between submaximal ADP-stimulated respiration
      rates, ROS generation and skeletal muscle insulin sensitivity in a model of type
      2 diabetes mellitus, the ZDF rat. Utilizing permeabilized muscle fibres we
      observed that submaximal ADP-stimulated respiration rates (250-2000 MUm ADP) were
      lower in ZDF rats than in lean controls, which coincided with decreased adenine
      nucleotide translocase 2 (ANT2) protein content. This decrease in submaximal ADP
      stimulated respiration occurred in the absence of a decrease in electron
      transport chain function. Treating ZDF rats with resveratrol improved skeletal
      muscle insulin resistance and this was associated with elevated submaximal ADP
      stimulated respiration rates as well as an increase in ANT2 protein content.
      These results coincided with a greater ability of ADP to attenuate mitochondrial
      ROS emission and an improvement in cellular redox balance. Together, these data
      suggest that mitochondrial dysfunction is present in skeletal muscle insulin
      resistance when assessed at submaximal ADP concentrations and that ADP dynamics
      may influence skeletal muscle insulin sensitivity through alterations in the
      propensity for mitochondrial ROS emission.

PMID- 24081155
TI  - Measuring cerebrovascular reactivity: what stimulus to use?
AB  - Cerebrovascular reactivity is the change in cerebral blood flow in response to a
      vasodilatory or vasoconstrictive stimulus. Measuring variations of
      cerebrovascular reactivity between different regions of the brain has the
      potential to not only advance understanding of how the cerebral vasculature
      controls the distribution of blood flow but also to detect cerebrovascular
      pathophysiology. While there are standardized and repeatable methods for
      estimating the changes in cerebral blood flow in response to a vasoactive
      stimulus, the same cannot be said for the stimulus itself. Indeed, the wide
      variety of vasoactive challenges currently employed in these studies impedes
      comparisons between them. This review therefore critically examines the
      vasoactive stimuli in current use for their ability to provide a standard
      repeatable challenge and for the practicality of their implementation. Such
      challenges include induced reductions in systemic blood pressure, and the
      administration of vasoactive substances such as acetazolamide and carbon dioxide.
      We conclude that many of the stimuli in current use do not provide a standard
      stimulus comparable between individuals and in the same individual over time. We
      suggest that carbon dioxide is the most suitable vasoactive stimulus. We describe
      recently developed computer-controlled MRI compatible gas delivery systems which
      are capable of administering reliable and repeatable vasoactive CO2 stimuli.

PMID- 24081156
TI  - Astroglial potassium clearance contributes to short-term plasticity of
      synaptically evoked currents at the tripartite synapse.
AB  - Astroglial processes enclose ~60% of CA1 hippocampal synapses to form the
      tripartite synapse. Although astrocytes express ionic channels, neurotransmitter
      receptors and transporters to detect neuronal activity, the nature, plasticity
      and impact of the currents induced by neuronal activity on short-term synaptic
      plasticity remain elusive in hippocampal astrocytes. Using simultaneous
      electrophysiological recordings of astrocytes and neurons, we found that single
      stimulation of Schaffer collaterals in hippocampal slices evokes in stratum
      radiatum astrocytes a complex prolonged inward current synchronized to synaptic
      and spiking activity in CA1 pyramidal cells. The astroglial current is composed
      of three components sensitive to neuronal activity, i.e. a long-lasting potassium
      current mediated by Kir4.1 channels, a transient glutamate transporter current
      and a slow residual current, partially mediated by GABA transporters and Kir4.1
      independent potassium channels. We show that all astroglial membrane currents
      exhibit activity-dependent short-term plasticity. However, only the astroglial
      glutamate transporter current displays neuronal-like dynamics and plasticity. As
      Kir4.1 channel-mediated potassium uptake contributes to 80% of the synaptically
      evoked astroglial current, we investigated in turn its impact on short-term
      synaptic plasticity. Using glial conditional Kir4.1 knockout mice, we found that
      astroglial potassium uptake reduces synaptic responses to repetitive stimulation
      and post-tetanic potentiation. These results show that astrocytes integrate
      synaptic activity via multiple ionic channels and transporters and contribute to
      short-term plasticity in part via potassium clearance mediated by Kir4.1
      channels.

PMID- 24081157
TI  - Corticospinal modulation induced by sounds depends on action preparedness.
AB  - A loud acoustic stimulus (LAS) presented during movement preparation can induce
      an early release of the prepared action. Because loud sound has been found to
      have an inhibitory effect on motor cortex excitability, it is possible that the
      motor cortex plays little role in the early release of prepared responses. We
      sought to shed new light on this suggestion by probing changes in corticospinal
      excitability after LAS presentation during preparation for an anticipatory
      action. Unexpectedly, we show that the changes in corticospinal excitability
      after LAS presentation are not fixed. Based on the magnitude of motor-evoked
      potentials elicited by transcranial magnetic and electric stimulation of the
      motor cortex, we demonstrate that the effects of auditory stimuli on
      corticospinal excitability depend on the level of readiness for action:
      inhibition in early preparation and facilitation close to movement onset. We also
      show that auditory stimuli can regulate intracortical excitability by increasing
      intracortical facilitation and reducing short-interval intracortical inhibition.
      Together, these findings indicate that, at least in part, the early release of
      motor responses by auditory stimuli involves the motor cortex.

PMID- 24081158
TI  - Tendon and skeletal muscle matrix gene expression and functional responses to
      immobilisation and rehabilitation in young males: effect of growth hormone
      administration.
AB  - We examined the effect of growth hormone (GH) on connective tissue of tendon and
      skeletal muscle during immobilisation and re-training in humans. Young men (20-30
      years; n = 20) were randomly assigned to daily recombinant human GH (rhGH) (33-50
      MUg kg(-1) day(-1)) or placebo (Plc), and had one leg immobilised for 2 weeks,
      followed by 6 weeks of strength training. The cross-sectional area (CSA), maximal
      muscle strength (maximal voluntary contraction, MVC) and biomechanical properties
      of the quadriceps muscle and patellar tendon were determined. Muscle and tendon
      biopsies were analysed for mRNA of collagen (COL1A1/3A1), insulin-like growth
      factors (IGF-1Ea/Ec), lysyl oxidase (LOX), matrix metalloproteases (MMP-2 and MMP
      9), decorin and tenascin-C. Fibril morphology was analysed by transmission
      electron microscopy (TEM) to detect changes in the fibril diameter distribution.
      In muscle, CSA and MVC declined with immobilisation and recovered with
      rehabilitation similarly in both groups. Likewise, both groups showed increased
      IGF-1Ea/Ec and COL1A1/3A1 expression in muscle during re-training after
      immobilisation compared with baseline, and the increase was more pronounced when
      subjects received GH. The tendon CSA did not change during immobilisation, but
      increased in both groups during 6 weeks of rehabilitation (~14%). A decline in
      tendon stiffness after immobilisation was observed only in the Plc group, and an
      increase during 6 weeks of rehabilitation was observed only in the GH group. IGF
      1Ea and COL1A1/3A1 mRNA increased with immobilisation in the GH group only, and
      LOX mRNA was higher in the GH group than in the Plc group after immobilisation.
      Both groups showed an increase in MMP-2 with immobilisation, whereas no changes
      in MMP-9, decorin and tenascin-C were observed. The tendon fibril diameter
      distribution remained unchanged in both groups. In conclusion, GH stimulates
      collagen expression in both skeletal muscle and tendon, abolishes the normal
      inactivity-related decline in tendon stiffness and LOX, and results in increased
      tendon CSA and stiffness during rehabilitation. GH has a matrix-stabilising
      effect during periods of inactivity and rehabilitation in humans.

PMID- 24081159
TI  - Endogenous zinc depresses GABAergic transmission via T-type Ca(2+) channels and
      broadens the time window for integration of glutamatergic inputs in dentate
      granule cells.
AB  - Zinc actions on synaptic transmission span the modulation of neurotransmitter
      receptors, transporters, activation of intracellular cascades and alterations in
      gene expression. Whether and how zinc affects inhibitory synaptic signalling in
      the dentate gyrus remains largely unexplored. We found that mono- and di-synaptic
      GABAergic inputs onto dentate granule cells were reversibly depressed by
      exogenous zinc application and enhanced by zinc chelation. Blocking T-type Ca(2+)
      channels prevented the effect of zinc chelation. When recording from dentate fast
      spiking interneurones, zinc chelation facilitated T-type Ca(2+) currents,
      increased action potential half-width and decreased spike threshold. It also
      increased the offset of the input-output relation in a manner consistent with
      enhanced excitability. In granule cells, chelation of zinc reduced the time
      window for the integration of glutamatergic inputs originating from perforant
      path synapses, resulting in reduced spike transfer. Thus, zinc-mediated
      modulation of dentate interneurone excitability and GABA release regulates
      information flow to local targets and hippocampal networks.

PMID- 24081160
TI  - Calcineurin inhibitor induces pain hypersensitivity by potentiating pre- and
      postsynaptic NMDA receptor activity in spinal cords.
AB  - Calcineurin inhibitors, such as cyclosporin A and tacrolimus (FK506), have played
      a pivotal role in the preservation of allograft function. However, these drugs
      can cause unexplained severe pain in patients, often referred to as calcineurin
      inhibitor-induced pain syndrome (CIPS). Although calcineurin can regulate NMDA
      receptor (NMDAR) activity, the causal relationship between spinal synaptic
      plasticity and CIPS remains unknown. In this study, we showed that systemic
      administration of FK506 (1.5 mg kg(-1) day(-1)) for 7 days in rats led to long
      lasting nociceptive and mechanical hypersensitivity. Whole-cell patch-clamp
      recordings in spinal cord slices revealed that FK506 treatment caused a large
      increase in the amplitude of NMDAR-mediated excitatory postsynaptic currents
      (EPSCs) of dorsal horn neurons evoked by dorsal root stimulation. The amplitude
      of NMDAR currents elicited by puff NMDA application to dorsal horn neurons was
      also significantly greater in FK506-treated than in vehicle-treated rats. The
      frequency of spontaneous and miniature EPSCs in most dorsal horn neurons was
      profoundly increased in FK506-treated rats and was reduced by blocking NMDARs.
      Furthermore, blocking GluN2A or GluN2B subunits similarly reduced the amplitude
      of evoked EPSCs and the frequency of miniature EPSCs in dorsal horn neurons of
      FK506-treated rats. In addition, intrathecal injection of an NMDAR antagonist or
      systemic administration of memantine effectively reversed nociceptive and
      mechanical hypersensitivity in FK506-treated rats. Our findings indicate that
      calcineurin inhibition increases glutamate-mediated nociceptive input by
      potentiating presynaptic and postsynaptic NMDAR activity in spinal cords. NMDAR
      antagonists may represent a new therapeutic option for the treatment of CIPS.

PMID- 24081161
TI  - Myosin filaments in smooth muscle cells do not have a constant length.
AB  - Myosin molecules from smooth muscle and non-muscle cells are known to self
      assemble into side-polar filaments in vitro. However, the in situ mechanism of
      filament assembly is not clear and the question of whether there is a unique
      length for myosin filaments in smooth muscle is still under debate. In this study
      we measured the lengths of 16,587 myosin filaments in three types of smooth
      muscle cells using serial electron microscopy (EM). Sheep airway and pulmonary
      arterial smooth muscle as well as rabbit carotid arterial smooth muscle were
      fixed for EM and serial ultra-thin (50-60 nm) sections were obtained. Myosin
      filaments were traced in consecutive sections to determine their lengths. The
      results indicate that there is not a single length for the myosin filaments;
      instead there is a wide variation in lengths. The plots of observation frequency
      versus myosin filament length follow an exponential decay pattern. Analysis
      suggests that in situ assembly of myosin filaments in smooth muscle is governed
      by random processes of linear polymerization and de-polymerization, and that the
      dynamic equilibrium of these processes determines the observed length
      distribution.

PMID- 24081163
TI  - Essential role for UVRAG in autophagy and maintenance of cardiac function.
AB  - AIMS: Ultraviolet irradiation resistance-associated gene (UVRAG) is a tumour
      suppressor candidate that regulates cell autophagy and endocytosis. However, the
      in vivo function of UVRAG remains poorly understood. We sought to determine the
      physiological role of UVRAG in the heart. METHODS AND RESULTS: We characterized
      mice with disruption of the UVRAG gene by piggyBac (PB) transposon insertion. PB
      construct was inserted into intron 14 of the UVRAG gene and disruption of UVRAG
      transcript was confirmed by reverse transcript-polymerase chain reaction.
      Immunoblotting revealed that UVRAG was deficient in multiple tissues. Autophagic
      flux was attenuated in UVRAG-deficient (UVRAG(PB/PB)) mouse embryonic
      fibroblasts. In UVRAG-deficient hearts, autophagosomes were accumulated and
      autophagic flux, assessed as the increased protein abundance of LC3 II in
      chloroquine-treated animals, was impaired. UVRAG-deficient mice were viable,
      fertile, and developmentally normal. However, they developed age-related
      cardiomyopathy associated with compromised cardiac function. In addition,
      inflammatory response was enhanced in UVRAG-deficient hearts. CONCLUSION:
      Collectively, our findings suggest that UVRAG is essential for the regulation of
      autophagy and maintenance of cardiac function.

PMID- 24081162
TI  - Modelling genetic reorganization in the mouse spinal cord affecting left-right
      coordination during locomotion.
AB  - The spinal neural circuit contains inhibitory (CINi) and excitatory (CINe)
      commissural interneurons with axons crossing the mid-line. Direction of these
      axons to the other side of the cord is controlled by axon guidance molecules,
      such as Netrin-1 and DCC. The cord also contains glutamatergic interneurons,
      whose axon guidance involves the EphA4 receptor. In EphA4 knockout (KO) and
      Netrin-1 KO mice, the normal left-right alternating pattern is replaced with a
      synchronized hopping gait, and the cord of DCC KO mice exhibits uncoordinated
      left and right oscillations. To investigate the effects of these genetic
      transformations, we used a computational model of the spinal circuits containing
      left and right rhythm-generating neuron populations (RGs), each with a
      subpopulation of EphA4-positive neurons, and CINi and CINe populations mediating
      mutual inhibition and excitation between the left and right RGs. In the EphA4 KO
      circuits, half of the EphA4-positive axons crossed the mid-line and excited the
      contralateral RG neurons. In the Netrin-1 KO model, the number of contralateral
      CINi projections was significantly reduced, while in the DCC KO model, the
      numbers of both CINi and CINe connections were reduced. In our simulations, the
      EphA4 and Netrin-1 KO circuits switched from the left-right alternating pattern
      to a synchronized hopping pattern, and the DCC KO network exhibited uncoordinated
      left-right activity. The amplification of inhibitory interactions re-established
      an alternating pattern in the EphA4 and DCC KO circuits, but not in the Netrin-1
      KO network. The model reproduces the genetic transformations and provides
      insights into the organization of the spinal locomotor network.

PMID- 24081165
TI  - Stem cell highways: signalling beats trafficking?

PMID- 24081166
TI  - Reactive oxygen species in the follicular fluid of subfertile women undergoing In
      Vitro Fertilization: a short narrative review.
AB  - Reactive Oxygen Species (ROS) are produced as a normal product of aerobic
      metabolism. Naturally, there is an array of protective mechanisms that neutralize
      ROS, while any potential imbalance between ROS and antioxidants results in
      oxidative stress. In an In Vitro Fertilization (IVF) setting, existing literature
      suggests a favorable outcome in terms of oocyte quality/maturation and
      fertilization rate with increased ROS levels, while other study groups have
      presented significant data on the detrimental effect of increased ROS
      concentration in the quality of embryos exposed and their potential to advance.
      In this study, we examine the conflicting views of the role of ROS in
      fertilization and embryo quality, especially through their concentration in the
      follicular fluid of subfertile women undergoing IVF. The current debate could
      possibly be attributed to the different assay methods and end-point outcomes
      employed by each research group, along with the noted limited number of the
      relevant studies published on the subject. Properly conducted studies can further
      validate and elicit the exact role of ROS as well as their association to female
      reproduction, and especially to women undergoing IVF. 

PMID- 24081167
TI  - Snakebite: the true disease burden has yet to be determined.

PMID- 24081164
TI  - Nitrite activates protein kinase A in normoxia to mediate mitochondrial fusion
      and tolerance to ischaemia/reperfusion.
AB  - AIMS: Nitrite (NO2(-)), a dietary constituent and nitric oxide (NO) oxidation
      product, mediates cardioprotection after ischaemia/reperfusion (I/R) in a number
      of animal models when administered during ischaemia or as a pre-conditioning
      agent hours to days prior to the ischaemic episode. When present during
      ischaemia, the reduction of nitrite to bioactive NO by deoxygenated haem proteins
      accounts for its protective effects. However, the mechanism of nitrite-induced
      pre-conditioning, a normoxic response which does not appear to require reduction
      of nitrite to NO, remains unexplored. METHODS AND RESULTS: Using a model of
      hypoxia/reoxygenation (H/R) in cultured rat H9c2 cardiomyocytes, we demonstrate
      that a transient (30 min) normoxic nitrite treatment significantly attenuates
      cell death after a hypoxic episode initiated 1 h later. Mechanistically, this
      protection depends on the activation of protein kinase A, which phosphorylates
      and inhibits dynamin-related protein 1, the predominant regulator of
      mitochondrial fission. This results morphologically, in the promotion of
      mitochondrial fusion and functionally in the augmentation of mitochondrial
      membrane potential and superoxide production. We identify AMP kinase (AMPK) as a
      downstream target of the mitochondrial reactive oxygen species (ROS) generated
      and show that its oxidation and subsequent phosphorylation are essential for
      cytoprotection, as scavenging of ROS prevents AMPK activation and inhibits
      nitrite-mediated protection after H/R. The protein kinase A-dependent protection
      mediated by nitrite is reproduced in an intact isolated rat heart model of I/R.
      CONCLUSIONS: These data are the first to demonstrate nitrite-dependent normoxic
      modulation of both mitochondrial morphology and function and reveal a novel
      signalling pathway responsible for nitrite-mediated cardioprotection.

PMID- 24081168
TI  - Statistical characteristics of anterior fontanelle size at birth of term Sri
      Lankan new borns: a descriptive cross sectional study.
AB  - INTRODUCTION: Assessing the anterior fontanelle size is an important component of
      routine neonatal examination. For meaningful interpretation of fontanelle size,
      normal reference values are essential. Normal values for the fontanelle size in
      Sri Lankan newborns are not available. OBJECTIVES: To investigate characteristics
      of anterior fontanelle size at birth in Sri Lankan babies. METHODS: A descriptive
      cross sectional study was carried out between October and November 2010.
      Horizontal and vertical dimensions of the anterior fontanelle were measured in
      2215 normal term babies, between 12 to 24 hours after birth. A practical and
      simple method was used to measure fontanelle size. Average fontanelle size was
      calculated by adding horizontal and vertical dimensions and dividing by two.
      RESULTS: Mean of the average fontanelle size for the total sample was 2.55 cm
      (for males 2.57 cm and for females 2.52 cm). Longitudinal dimension was
      significantly higher than the horizontal in both sexes (p<0.001). Frequency
      distribution curves of fontanelle size followed a normal distribution in both
      sexes. The ninety seventh centile and third centile for the average fontanelle
      size were 4.5 cm and 0.9 cm respectively. CONCLUSIONS: Babies with an average
      anterior fontanelle size more than 4.5 cm or less than 0.9 cm need further follow
      up. Further studies are needed to evaluate the accuracy of these cut off values.

PMID- 24081169
TI  - Incidence and risk factors of falls among the elderly in the District of Colombo.
AB  - OBJECTIVES: To assess the incidence and risk factors of falls among the elderly
      in the District of Colombo. METHODS: Incidence of falls was assessed by a
      community based descriptive study with prospective follow up. Risk factors for
      falls were assessed by a nested case control study. Participants above 65 years
      residing in 40 Grama Niladhari Divisions in the Colombo district (n=1200) were
      assessed for falls and followed up for four months. Those who had falls were
      selected as cases (n=151), while two controls per case were selected from others.
      MEASUREMENTS: Tests for gait problems, disability, cognitive impairment and
      vision. RESULTS: The incidence rate of falls was 492 per 1000 person years (95%
      CI 448-536). Risk factors for falls identified in the multivariate analysis were
      falls in the previous year (OR 4.67), high disability level (OR 2.04) and high
      house risk level (OR 1.68). CONCLUSIONS: The high incidence of falls among the
      elderly reported in this study and the preventable risk factors identify /
      indicate the necessity and feasibility of their prevention.

PMID- 24081170
TI  - Prevalence of enterobiasis among primary school children in Ragama, Sri Lanka.
AB  - OBJECTIVES: To determine the prevalence of enterobiasis among school children in
      Ragama Medical Officer of Health (MOH) region and the association between
      clinical features, potential risk factors and infection status. DESIGN: Cross
      sectional study. SETTING: School based. Participants 260 school children aged 5-7
      years, attending five state schools in the Ragama MOH region. MAIN OUTCOME
      MEASURES: Prevalence of Enterobius vermicularis infection as diagnosed using
      adhesive cellophane tapes on the perianal skin on 2 consecutive days. RESULTS:
      The overall prevalence of enterobiasis was 38%. The risk factors significant on a
      univariate analysis were male gender, maternal under-education, non-permanency of
      paternal employment, more household members, more siblings in a family, more
      persons sleeping with an index child and lack of recent deworming. On a
      multivariate model more household members, more children in a household, more
      persons sleeping with the index child, non-permanency of paternal employment and
      lack of recent deworming were significantly associated with infection. None of
      the clinical manifestations evaluated (peri-anal itching, insomnia, abdominal
      pain, and enuresis) showed a significant association with enterobiasis.
      CONCLUSIONS: Enterobiasis is highly prevalent among primary school children in
      Ragama.

PMID- 24081171
TI  - Substance use disorders among mentally ill patients in a General Hospital in Sri
      Lanka: prevalence and correlates.
AB  - OBJECTIVES: To determine the prevalence, and demographic and clinical correlates
      of substance use disorders among the mentally ill. DESIGN AND SETTING: Cross
      sectional analytical study. Data were collected from consecutive patients treated
      at a Tertiary care Psychiatry Unit, Western Province, Sri Lanka using an
      interview schedule administered by a senior registrar in psychiatry.
      MEASUREMENTS: Diagnosis was based on ICD 10 criteria and the Clinician Rating
      Scale: Alcohol Use Scale (AUS) and the Drug Use Scale (DUS). The data were
      analysed using SPSS and WinPepi software programmes, utilising the chi squared, t
      test and median test. RESULTS: Among a sample of 325 patients, 66% were male; 33%
      were diagnosed with depressive disorder, 30% with schizophrenia, 23% with bipolar
      affective disorder and 13% with other disorders. Prevalence of comorbid substance
      use disorders was 43% (95% CI 38 - 49%). Alcohol was the commonest type of
      substance used. Those who had a comorbid substance use diagnosis were more likely
      to be male, have a lower educational level, be unemployed and have a poorer level
      of social support. They were also found to have poorer treatment adherence,
      increased number of hospital admissions and an increased association with
      episodes of violence. CONCLUSION: A significant proportion of patients were found
      to have a comorbid substance use diagnosis and associated complications. These
      findings have important implications for service provision for mentally ill
      patients with a comorbid substance use disorder.

PMID- 24081173
TI  - Use of culture and immunochromatographic technique for diagnosis of
      trichomoniasis in Sri Lanka.
AB  - As a majority of the trichomoniasis patients are asymptomatic, laboratory tests
      are crucial in case detection. The usefulness of culture and
      immunochromatographic technique (ICT) compared to microscopy for detection of
      trichomoniasis in Sri Lanka was assessed. Females (16-45 years) from Colombo
      district were screened for Trichomonas vaginalis using three laboratory tests
      namely, microscopy of wet smear, Trichomonas liquid culture and ICT (OSOM(r)
      trichomonas rapid test). Trichomoniasis by at least one test being positive was
      4.8%. Microscopy, culture and ICT detected 2.8%, 4.2% and 10% cases respectively.
      Microscopy missed 32% of culture positives. ICT is a simple, practical and
      reliable alternative to microscopy in laboratory diagnosis of trichomoniasis. 

PMID- 24081172
TI  - Accuracy of ultrasound estimated fetal weight formulae to predict actual
      birthweight after 34 weeks: prospective validation study.
AB  - OBJECTIVES: Late onset fetal growth restriction is often missed and is
      responsible for most intrauterine deaths. Ultrasound fetal biometry is routinely
      used to calculate estimated fetal weight (EFW). The aim of this study was to
      determine the accuracy of established ultrasound EFW formulae to identify small
      and large for gestational age fetuses when used after 35 weeks gestation.
      METHODS: This was a prospective validation study done between January 2012 and
      July 2012 at General Hospital Ampara. An ultrasound examination was performed and
      fetal biometry was documented within one week before the delivery in well dated
      pregnancies. The mean of the differences between ultrasound EFW derived from 9
      formulae and true birthweight and their standard error of mean (SE) were
      calculated for each formula. Systematic measurement error was assumed to exist if
      zero lay outside the mean difference +/- 2SE. To show the EFW frequency
      distribution, z-scores were calculated as the number of standard deviations an
      observed EFW measurement deviated from the mean for gestation. RESULTS: A total
      of 393 pregnancies at gestational age between 35 and 41 weeks were recruited.
      Mean gestational age at the ultra sound scan was 39.36 weeks SD (1.05). All EFW
      formulae either under or over estimated the birthweight in singleton pregnancies.
      Almost all the formulae overestimated the fetal weight in low birthweight babies
      whilst underestimating the fetal weight in birthweight >3500g. Campbell formula
      remained the only EFW formula without systematic error when measuring babies
      between 2500g and 3500g. None of the EFW z-scores were normally distributed.
      CONCLUSIONS: This study found that all routinely used EFW formulae would either
      over or under estimate the fetal weight. Until an optimum EFW formula that suits
      the Sri Lankan population is determined, interpretation of ultrasound EFW should
      be done cautiously, especially in small for gestational age babies.

PMID- 24081174
TI  - Improvised condom catheter with a draining channel for management of atonic post
      partum haemorrhage.
AB  - Primary postpartum haemorrhage (PPH) is one of the five leading causes of
      maternal mortality in both developed and developing countries [1] . During the
      last two decades various uterine taponade devices have been used successfully in
      the management of PPH [2-5]. Success rates for the control of postpartum bleeding
      have ranged from 71% to 87% [6, 7]. So far, the Bakri balloon is the only balloon
      product that is specifically designed for 'the control of postpartum uterine
      bleeding' (Cook Medical; enclosed instruction leaflet J-SOS1106). It has a
      drainage lumen which allows real-time assessment of ongoing blood loss above the
      level of the bulb and may prevent delayed treatment. This advantage is not
      present in the condom catheter. We report an improvised version of the condom
      catheter with a draining channel which was successfully used to manage two cases
      of PPH with uterine atony. 

PMID- 24081175
TI  - Heterotopic brain tissue in the sacrococcygeal region.

PMID- 24081176
TI  - Amyloidosis associated with HIV infection.

PMID- 24081177
TI  - A woman with dengue encephalitis.

PMID- 24081178
TI  - Kinetic and mechanistic studies on reactions of diruthenium(II,III) with
      biologically relevant reducing agents.
AB  - Diruthenium(ii,iii)-tetracarboxylates have shown promising anticancer properties
      as metallotherapeutics. On the basis of the role that bio-reducing agents may
      play on the mode of action of ruthenium-based anticancer drugs, we performed
      detailed kinetic studies on the reaction of ascorbic acid and glutathione with
      the [Ru2(RCOO)4](+) paddlewheel framework by using the non-drug, diaqua complex
      ion [Ru2(CH3COO)4(H2O)2](+). In the presence of the reducing agents, the diaqua
      Ru2 species first undergo a ligand substitution reaction by which the axially
      coordinated water is displaced by the reducing agent. In both cases, this
      reaction is followed by an intra-molecular electron transfer process during which
      the metal-metal center is reduced from Ru2(5+) to Ru2(4+) and the reducing agent
      is oxidized. Product analyses were performed with the application of ESI-MS and
      (1)H-NMR techniques. Rate and activation parameters are reported for the
      different reaction steps. 

PMID- 24081180
TI  - A history of clinical biochemistry through the eye of an enzyme.

PMID- 24081181
TI  - Lipoprotein lipase activity in heterozygotes for lipoprotein lipase gene
      mutations reveals a gender bias.
AB  - BACKGROUND: Familial lipoprotein lipase (LPL) deficiency is a very rare autosomal
      recessive disorder characterized by marked elevation of plasma triglyceride
      concentrations. Since 1989, a variety of mutations have been reported in affected
      patients. Studies on subjects with heterozygous LPL deficiency, on the other
      hand, have been limited. METHODS: We examined post-heparin plasma LPL activity in
      15 subjects with heterozygous LPL deficiency. RESULTS: The heterozygotes
      exhibited normal or slightly elevated plasma triglyceride concentrations. The
      mean LPL activity was reduced by 25% in the heterozygotes relative to controls.
      Interestingly, LPL activity was reduced specifically in female heterozygotes.
      CONCLUSION: LPL activity is decreased in female, but not in male, subjects
      heterozygous for a number of different LPL gene mutations.

PMID- 24081183
TI  - Insulin-like growth factor-II and insulin-like growth factor binding protein-2
      prospectively predict longitudinal elevation of HDL-cholesterol in type 2
      diabetes.
AB  - INTRODUCTION: Associations of insulin-like growth factor-II (IGF-II) and insulin
      like growth factor binding protein-2 (IGFBP-2) with cardiovascular risk have been
      inadequately studied. We hypothesized that IGF-II and IGFBP-2 associate with
      longitudinal trends in lipid profiles in type 2 diabetes patients. SUBJECTS AND
      METHODS: Four hundred and eighty nine subjects with type 2 diabetes (age 27-87
      years) from the Salford Diabetes Cohort were studied. Longitudinal clinical
      information was extracted for an eight-year period (2002-2009) from an integrated
      electronic dataset of primary care and hospital data. RESULTS: There were 294
      male subjects and mean age was 62.9 years. At baseline, IGF-II concentration was
      602 ng/mL. HDL cholesterol at baseline was associated with log-IGF-II
      concentration in a model adjusted for age, gender, baseline body-mass index
      (BMI), estimated glomerular filtration rate (eGFR) and lipid-lowering therapy.
      IGFBP-1 and IGFBP-2 were associated with high HDL-cholesterol. A higher
      circulating IGF-II concentration at baseline was also associated with
      longitudinal increase in HDL-cholesterol in mixed-effects regression analyses
      independent of IGF-I, IGFBP-1, IGFBP-2, IGFBP-3, age, gender, eGFR, BMI and lipid
      lowering therapy. Log-transformed baseline concentrations of IGFBP-1 and IGFBP-2
      were also associated with longitudinal elevation in HDL-cholesterol. No
      association was observed for IGF-II or IGFBP-2 with longitudinal LDL cholesterol
      trends. CONCLUSION: Our analyses based on 'real world' data demonstrate that
      higher baseline IGF-II and IGFBP-2 predict increased HDL concentration over time,
      implicating IGF-II in modulation of circulating HDL-cholesterol concentrations.

PMID- 24081184
TI  - Cascade testing of primary care blood samples with hyperferritinaemia identifies
      subjects with iron overload and porphyria cutanea tarda.
AB  - INTRODUCTION: Serum ferritin is routinely used as a first line test for iron
      status. Testing subjects with low pre-test probability often results in
      unexpected abnormal results. Raised ferritin is typically found in subjects with
      iron overload, liver disease, malignancy or inflammation. We sought to determine
      whether primary care patients with high ferritin had either porphyria cutanea
      tarda (PCT) or hereditary haemochromatosis (HH). METHODS: Redundant serum samples
      were collected from consecutive specimens with high ferritin (>500 ug/L) which
      had been received from primary care sources. Samples were analysed for serum iron
      and iron-binding capacity and for porphyrins by fluorescence scanning and HPLC.
      RESULTS: There were 240 samples (91 females, 149 males) which represented 2.7% of
      total over the collection period. Serum iron was 17.3 (18.9) umol/L (median
      (IQR)), TIBC 47.3 (14.2) umol/L and transferrin saturation 35.7 (41.1) %. There
      were 87/240 (36%) with transferrin saturation >45% (57 males, 30 females). Of the
      samples 19/236 (8%) were positive for porphyrins by spectrofluorimetry and 14/15
      (4 insufficient sample) had total porphyrins >11.2 nmol/L (40(63) median (IQR))
      with 3/15 (1.25%) having a typical pattern for PCT. DISCUSSION: This study
      demonstrates the feasibility of cascading tests using laboratory protocols and
      confirms the ability to identify potential cases. However, further studies for HH
      genotype and urine and stool porphyrin analysis will be necessary to confirm the
      diagnoses.

PMID- 24081185
TI  - Removal of the gadolinium interference from the measurement of selenium in human
      serum by use of collision cell quadrupole inductively coupled plasma mass
      spectrometry (Q-ICP-MS).
AB  - BACKGROUND: Measurement of selenium in serum is an important clinical biomarker
      of nutritional status. The presence of gadolinium (Gd) in samples following
      administration of the contrast agents used for magnetic resonance imaging (MRI)
      results in a significant positive bias when using quadrupole inductively coupled
      plasma mass spectrometry (Q-ICP-MS). METHODS: Three instrumental set-ups were
      assessed: standard mode with no collision gas and collision cell mode with either
      a hydrogen:helium mixture or hydrogen. The effect of Gd on the selenium (Se)
      signal was assessed using external quality assurance (EQA) specimens and internal
      quality control (IQC) materials, both unspiked and spiked with Gd. Serum
      previously shown to contain high concentrations of Gd-containing contrast agents
      were also analysed. RESULTS: Recoveries of Se in the spiked compared to the
      unspiked samples were: between 500% and 1300% using standard mode; 100% and
      29,000% using collision cell mode with hydrogen:helium mixture; and between 99%
      and 103% using hydrogen. The use of H2 in the collision cell provided accurate
      results, indicating that the charge exchange reaction (CER) of Gd(2+) with H2
      removes this interference. Analysis of patient serum known to contain the Gd
      contrast agent using the method gave results within the selenium reference range
      (adults 0.89-1.65 umol/L). The presence of Gd, as low as 0.2 mg/L, in serum
      samples causes a positive interference on the measurement of Se by ICP-MS.
      CONCLUSIONS: Using a CER mode with pure H2 in the collision cell it was possible
      to fully remove the interference due to Gd(2+) from the signal for Se.

PMID- 24081186
TI  - Antioxidative system in the erythrocytes of preterm neonates with sepsis: the
      effects of vitamin E supplementation.
AB  - BACKGROUND: Vitamin E is routinely supplemented to preterm babies, including
      those with neonatal sepsis. Our aim was to examine the effects of neonatal sepsis
      and vitamin E on antioxidative system (AOS) in the blood. METHODS: A prospective,
      randomized, open label study involved 65 preterm neonates (control/sepsis -
      34/31), which were divided into two subgroups - non-supplemented and supplemented
      with vitamin E (25 IU/day for 60 days). The activities of superoxide dismutase,
      catalase (CAT), glutathione peroxidase (GPx), and glutathione reductase (GR) were
      determined in erythrocytes at days 0, 30, and 60, following sepsis diagnosis.
      RESULTS: There was no difference in the activity of AOS between controls and
      neonates with ongoing sepsis. At 60 days, septic neonates showed higher CAT
      activity compared to controls (P = 0.027), and lower GPx activity compared to 0
      days (P = 0.022). The later was mitigated by vitamin E, which on the other hand
      provoked lower GPx activity at 30 days, compared to untreated septic neonates (P
      = 0.014). In addition, vitamin E suppressed GR activity in septic neonates (P =
      0.025 and P = 0.017 at 30 and 60 days). Finally, vitamin E supplementation in
      control neonates provoked a significant increase of GPx activity (P = 0.015 at 60
      days). CONCLUSIONS: The absence of altered redox settings in the blood of
      neonates during sepsis episode, and vitamin E-provoked decrease in the activity
      of some components of AOS, suggest that the supplementation of vitamin E in these
      patients might not be rational.

PMID- 24081187
TI  - Measurement of plasma viscosity by free oscillation rheometry: imprecision,
      sample stability and establishment of a new reference range.
AB  - BACKGROUND: Plasma viscosity (PV) is used in the investigation of hyperviscosity
      syndrome. We have evaluated the performance of a new bench-top free oscillation
      rheometer, ReoRox from Medirox, and established a new reference range. METHODS:
      Performance of the free oscillation rheometry (FOR) method was evaluated
      examining within-run and between-run imprecision, duration of measurement and
      operator simplicity. Furthermore, influence of storage on the PV measurements was
      assessed and a reference range based on plasma from 585 healthy men and women was
      established. RESULTS: Imprecision of the free oscillation rheometer was
      comparable to other viscometers and performance of the instrument was satisfying.
      The non-parametrical reference range established was 1.22-1.44 mPa s at 37C
      (2.5th and 97.5th percentiles). CONCLUSIONS: We have established a FOR PV
      reference range to support clinical decision-making. Furthermore, we found high
      pre-analytical stability of the samples and an analytical imprecision comparable
      to other PV methods.

PMID- 24081188
TI  - E-mental health: a rapid review of the literature.
AB  - OBJECTIVE: The authors conducted a review of the literature on e-mental health,
      including its applications, strengths, limitations, and evidence base. METHODS:
      The rapid review approach, an emerging type of knowledge synthesis, was used in
      response to a request for information from policy makers. MEDLINE was searched
      from 2005 to 2010 by using relevant terms. The search was supplemented with a
      general Internet search and a search focused on key authors. RESULTS: A total of
      115 documents were reviewed: 94% were peer-reviewed articles, and 51% described
      primary research. Most of the research (76%) originated in the United States,
      Australia, or the Netherlands. The review identified e-mental health applications
      addressing four areas of mental health service delivery: information provision;
      screening, assessment, and monitoring; intervention; and social support.
      Currently, applications are most frequently aimed at adults with depression or
      anxiety disorders. Some interventions have demonstrated effectiveness in early
      trials. Many believe that e-mental health has enormous potential to address the
      gap between the identified need for services and the limited capacity and
      resources to provide conventional treatment. Strengths of e-mental health
      initiatives noted in the literature include improved accessibility, reduced costs
      (although start-up and research and development costs are necessary), flexibility
      in terms of standardization and personalization, interactivity, and consumer
      engagement. CONCLUSIONS: E-mental health applications are proliferating and hold
      promise to expand access to care. Further discussion and research are needed on
      how to effectively incorporate e-mental health into service systems and to apply
      it to diverse populations.

PMID- 24081196
TI  - The effects of perioperative inhaled iloprost on pulmonary hypertension with
      congenital heart disease.
AB  - OBJECTIVES: The treatment of choice for congenital heart disease (CHD) with
      pulmonary arterial hypertension (PAH) is still controversial. We assessed the
      efficacy and safety of perioperative inhaled iloprost therapy in CHD with PAH.
      METHODS: Among 45 patients with a ventricular septal defect and/or an atrial
      septal defect with PAH, 28 patients were treated with inhaled iloprost before and
      after surgery. Perioperative clinical parameters and plasma B-type natriuretic
      peptide (BNP) were evaluated. RESULTS: No statistical difference in the estimated
      right ventricular systolic pressure (e-RVP), the e-RVP-to-systemic pressure
      ratio, and preoperative BNP levels between the iloprost group and the control
      group were found. Among the iloprost group, oxygen saturation was increased
      significantly after iloprost inhalation therapy (p = 0.0052). The iloprost group
      was also significantly correlated with less use of inhaled nitric oxide in the
      immediate postoperative period compared to the control group (p = 0.021). The
      durations of mechanical ventilation (p = 0.018), ICU stay (p = 0.005), and chest
      tube use (p = 0.039) were significantly shorter in the iloprost group compared to
      the control group. The plasma BNP, checked on 7th day of postoperatively, was
      lower in the iloprost group than in the control group (p = 0.008). CONCLUSION:
      Perioperative inhaled iloprost therapy showed the benefit of cardiac functional
      improvement and early weaning of postoperative supportive care in the management
      of CHD with PAH.

PMID- 24081197
TI  - Radical Pd(III)/Pd(I) reductive elimination in palladium sequences.
AB  - Open-shell mechanisms are often at work in catalytic sequences involving first
      row transition metals while usually not considered in palladium chemistry. Herein
      a computational study suggests their possible relevance in catalytic methods
      involving paramagnetic Pd(iii) intermediates. Indeed C-C bond forming reductive
      elimination previously thought to occur in Pd(iv) complexes has lower barriers in
      neutral, radical Pd(iii) intermediates instead. These species could form upon
      addition on Pd(ii) of an aryl radical generated via single electron transfer from
      a photo-active ruthenium complex and have the perfect stereoelectronic
      arrangement to smoothly undergo the coupling process. 

PMID- 24081194
TI  - Lower risk of cardiovascular events in postmenopausal women taking oral estradiol
      compared with oral conjugated equine estrogens.
AB  - IMPORTANCE: Little is known about the comparative cardiovascular safety of oral
      hormone therapy products, which impedes women from making informed safety
      decisions about hormone therapy to treat menopausal symptoms. OBJECTIVE: To
      compare the relative clinical cardiovascular safety of 2 commonly used oral
      estrogen drugs-conjugated equine estrogens (CEEs) and estradiol. DESIGN, SETTING,
      AND PARTICIPANTS: Population-based, case-control study from January 1, 2003, to
      December 31, 2009, comparing cardiovascular event risk associated with current
      CEEs and estradiol use in a large health maintenance organization in which the
      preferred formulary estrogen changed from CEEs to estradiol during the course of
      data collection. Participants were 384 postmenopausal women aged 30 to 79 years
      using oral hormone therapy. MAIN OUTCOMES AND MEASURES: Incident venous
      thrombosis was the primary clinical outcome, and incident myocardial infarction
      and ischemic stroke were secondary outcomes. As validation, an intermediate
      clotting phenotype, the endogenous thrombin potential-based normalized activated
      protein C sensitivity ratio, was measured in plasma of controls. RESULTS: We
      studied 68 venous thrombosis, 67 myocardial infarction, and 48 ischemic stroke
      cases, with 201 matched controls; all participants were current users of oral
      CEEs or estradiol. In adjusted analyses, current oral CEEs use compared with
      current oral estradiol use was associated with an increased venous thrombosis
      risk (odds ratio, 2.08; 95% CI, 1.02-4.27; P = .045) and an increased myocardial
      infarction risk that did not reach statistical significance (odds ratio, 1.87;
      95% CI, 0.91-3.84; P = .09) and was not associated with ischemic stroke risk
      (odds ratio, 1.13; 95% CI, 0.55-2.31; P = .74). Among 140 controls, CEEs users
      compared with estradiol users had higher endogenous thrombin potential-based
      normalized activated protein C sensitivity ratios (P < .001), indicating a
      stronger clotting propensity. CONCLUSIONS AND RELEVANCE: In an observational
      study of oral hormone therapy users, CEEs use was associated with a higher risk
      of incident venous thrombosis and possibly myocardial infarction than estradiol
      use. This risk differential was supported by biologic data. These findings need
      replication and suggest that various oral estrogen drugs may be associated with
      different levels of cardiovascular risk.

PMID- 24081199
TI  - Assessing efficacy/effectiveness and safety/tolerability profiles of adjunctive
      pramipexole in bipolar depression: acute versus long-term data.
AB  - Bipolar depression represents the most difficult-to-treat phase of bipolar
      disorder, mood-stabilizing compounds and second-generation antipsychotics being
      only partially effective, whereas the use of antidepressants is highly
      controversial because of risks of inefficacy, switching, rapid cycling, and
      increased suicidality. Among various augmentative pharmacological treatments,
      compounds with dopamine-enhancing activity have been shown to be variably
      beneficial in the treatment of bipolar depression with drug-resistance features.
      In particular, pramipexole - a dopamine D2/D3 receptor agonist - showed
      antidepressant properties in bipolar depressed patients in both randomized
      controlled trials and open acute and follow-up reports. The present review aims
      to provide an updated perspective on the use of adjunctive pramipexole in bipolar
      depression, taking into account randomized-controlled trials, as well as open
      naturalistic studies, with a specific focus on the evaluation of acute versus
      long-term data in terms of effectiveness and tolerability. Despite methodological
      differences, short-term studies support the acute efficacy and
      tolerability/safety of adjunctive pramipexole, whereas open extended observations
      seem to confirm the effectiveness of the compound, with some additional concern
      in terms of safety and tolerability issues. Adjunctive pramipexole may be a valid
      option in both the acute and the long-term treatment of drug-resistant bipolar
      depression, with possible superior tolerability in the short term. 

PMID- 24081198
TI  - Electronic approaches to restitute vision in patients with neurodegenerative
      diseases of the retina.
AB  - Degenerations of the outer retina are hereditary diseases leading to significant
      loss of vision. Several concepts of active electrical stimulation of the
      remaining retinal network resulted in the development of retinal visual implants
      and prosthetic vision. Subretinal and epiretinal visual implants are currently
      the leading approaches in restoring functional vision in blind humans with
      retinitis pigmentosa or other outer retinal degenerations. This review gives a
      short overview about the principles, advantages, limitations and vision outcome
      of the up-to-date published artificial vision by electronic visual implants, as
      well as their known biocompatibility and safety issues.

PMID- 24081200
TI  - An evaluation of nest-building behavior by sanctuary chimpanzees with access to
      forested habitats.
AB  - All of the great apes build nests, but captive chimpanzees rarely have vegetation
      from which to build nests. The forested environment at Chimp Haven does allow
      captive chimpanzees to build nests of natural vegetation. Between February 2007
      and December 2010, 238 nests were found in 2 forested habitats. Nests were made
      of naturally available vegetation, and more nests were made on the ground than in
      the trees (Z = 7.27, p < 0.001); nests were also built in the interior forest
      rather than on the periphery (Z = 7.06, p < 0.001). There was no correlation
      between the number of months in the habitat and the nests built per chimpanzee
      (rs = -0.07, p = 0.52). More nests were observed when more wild-born females were
      in the group (rs = 0.27, p = 0.01), and during warmer temperatures (rs = 0.45, p
      < 0.001). These findings support the goal of naturalistic environments in
      suitable climates for captive chimpanzees.

PMID- 24081201
TI  - Synthesis of benzimidazoles by potassium tert-butoxide-promoted intermolecular
      cyclization reaction of 2-iodoanilines with nitriles.
AB  - The synthesis of benzimidazoles by intermolecular cyclization reaction of 2
      iodoanilines with nitriles has been developed. These reactions proceeded without
      the aid of any transition metals or ligands and just using KOBu(t) as the base. A
      variety of substituted benzimidazole derivatives can be synthesized by the
      approach. 

PMID- 24081202
TI  - Association of hemoglobin E-Saskatoon with hemoglobin S: report of the first case
      found in Brazil.

PMID- 24081203
TI  - Simultaneous quantification of anidulafungin and caspofungin in plasma by an
      accurate and simple liquid chromatography tandem mass-spectrometric method.
AB  - INTRODUCTION: Echinocandins are a valuable addition for the treatment of invasive
      fungal infections, as they are efficacious, demonstrate low toxicity, and have
      limited drug-drug interactions. In specific clinical situations when altered
      pharmacokinetics can be expected or dosing guidelines are conflicting, it may be
      useful to measure concentrations. For this purpose, a liquid chromatography
      tandem mass-spectrometric method to measure anidulafungin and caspofungin in
      ethylenediaminetetraacetic acid plasma was developed. METHODS: The method was
      developed on a Thermo Fisher TSQ Quantum LC-MS/MS. For separation, a BetaBasic C4
      (100 mm * 3.0 mm; 5 MUm) analytical column was used. Sample preparation consisted
      of protein precipitation directly in the autosampler vial. The internal standard
      aculeacin A is structurally related, not used in humans, and commercially
      available. The method was validated according to the guidelines for bioanalytical
      method validation of the Food and Drug Administration. RESULTS: The method was
      accurate (bias ranging from -3.0% to 1.9%) and precise (within-run and between
      run coefficients of variation of 2.2% to 7.7% and 1.6% to 9.0%, respectively).
      All calibration curves were linear over a range of 0.5-10.0 mg/L for
      anidulafungin and 0.1-20.0 mg/L for caspofungin, and if necessary, samples can be
      diluted 10-fold. The samples were stable for 3 freeze-thaw cycles, with a bias
      ranging from 0.6% to 11%. The maximum bias from the worst storage condition, 72
      hours at room temperature, was -14.7%. In patient samples, anidulafungin peak
      concentrations ranged from 2.8 to 8.6 mg/L (n = 20) and trough concentrations
      ranged from 1.0 to 4.7 mg/L (n = 79). The measured caspofungin concentrations
      ranged from 1.9 to 7.3 mg/L (n = 20). CONCLUSIONS: The method developed has a
      straightforward sample preparation and uses a structural analog as the internal
      standard. This method has been applied successfully for the measurement of
      anidulafungin and caspofungin concentrations in patient samples, both for
      clinical practice and for research.

PMID- 24081204
TI  - Multiple regression analysis of factors predicting mycophenolic acid free
      fraction in 91 adult organ transplant recipients.
AB  - BACKGROUND: Mycophenolic acid (MPA) is an antirejection drug used in various
      types of solid organ transplants. MPA is extensively bound to albumin, and free
      MPA is thought to be the primary immunosuppressive agent. Little is known of what
      contributes to the wide interindividual variability in the observed MPA free
      fraction (MPAf) in humans. The purpose of this study was to determine, using
      multiple regression analysis of demographic and laboratory variables that are
      routinely collected during clinic visits, patient factors that predict MPAf in a
      large sample (n = 91) of organ transplant recipients. METHODS: Age, weight,
      height, total daily MPA dose, albumin, serum creatinine (SrCr), and MPAf were
      obtained from islet (n = 16), kidney (n = 28), and heart/lung (n = 47) transplant
      recipients. Multiple linear regression analysis and the The Spearman rank
      correlation were conducted using SigmaStat (version 3.5 for Windows).
      Significance was set a priori at P = 0.05. RESULTS: The pooled data can be
      described as (mean +/- SD) follows: age (52 +/- 13 years), weight (72 +/- 15 kg),
      height (169 +/- 9 cm), total daily MPA dose (1632 +/- 667 mg), albumin (42 +/- 7
      g/L), SrCr (112 +/- 34 umol/L), and MPAf (2.9% +/- 3.5%). Multiple regression of
      all commonly acquired variables generated the following equation: MPAf = 1.865 +
      (0.0357 * age (yrs)) + (0.0125 * weight (kg)) - (0.0202 * height (cm)) -
      (0.000323 * total daily dose (mg)) + (0.0122 * albumin (g/L)) + (0.0160 * SrCr
      (umol/L)) (r = 0.06), but none of the variables were significant predictors of
      MPAf (P > 0.05). The Spearman rank correlation of each individual variable
      confirmed lack of significant correlation with MPAf. CONCLUSIONS: To our
      knowledge, this is the first study attempting to describe factors predicting MPAf
      in adult organ transplant recipients involving a large sample size. The novel
      findings of lack of significant predictors warrant further investigations using
      additional patient factors.

PMID- 24081205
TI  - A UPLC-MS/MS method for therapeutic drug monitoring of etonogestrel.
AB  - INTRODUCTION: Etonogestrel (ENG) is a progestin used in the contraceptive vaginal
      ring NuvaRing and the subdermal implant Implanon. A sensitive method for
      measuring ENG is useful for further investigating the progestin's
      pharmacokinetics with these alternative contraceptive formulations and generating
      important information about possible continued efficacy or potential failure to
      remove the subdermal implant. METHODS: Standards and serum samples were spiked
      with D8-progesterone (internal standard) and subsequently extracted with
      dichloromethane, dried, and reconstituted in 25% methanol with formic acid. ENG
      was analyzed by positive electrospray ionization in multiple reaction monitoring
      mode with a run time of 5.5 minutes using a C18 BEH column. The mobile phase was
      a gradient of water:acetonitrile, with 0.1% formic acid. The method was applied
      successfully to study the pharmacokinetics of ENG during vaginal ring use. The
      method was also used in routine patient care to assess ENG levels. RESULTS: The
      method is linear from 50 to 2000 pg/mL. The limits of detection and
      quantification are 25 and 50 pg/mL, respectively. There was no observed
      ionization suppression within the linear range of the assay, and the average
      recovery was 87%. Serum ENG levels of n = 3 subjects were all within the linear
      range of the assay for a total study period of 42 days after insertion of the
      ring. Of n = 20 patients with nonpalpable subdermal implants, n = 13 had ENG
      levels >25 pg/mL, whereas n = 7 had levels <25 pg/mL. CONCLUSIONS: We developed a
      rapid, sensitive, and robust ultra performance liquid chromatography-tandem mass
      spectometry (UPLC-MS/MS) method for the quantification of ENG in serum that is
      useful to study the progestin's pharmacokinetics and inform physicians about
      successful implantation or potential failure to remove a subdermal device.

PMID- 24081206
TI  - Tacrolimus exposure and mycophenolate pharmacokinetics and pharmacodynamics early
      after liver transplantation.
AB  - BACKGROUND: Mycophenolic acid (MPA) and tacrolimus play important roles in
      immunosuppressive therapy after solid organ transplantation (Tx) and show large
      intra- and interindividual pharmacokinetic (PK) variabilities. The purpose of
      this study was to describe the intra- and interindividual variabilities of MPA
      and tacrolimus PKs during the first 3 weeks after adult liver transplantation.
      Furthermore, inosine monophosphate dehydrogenase activity was investigated.
      MATERIALS: This study describes PK and pharmacodynamic parameters of MPA and the
      PKs of tacrolimus in 16 liver transplant recipients, in 4 follow-up periods (I
      IV). RESULTS: The area under the concentration-time curve (AUC(0-12 hours)) for
      tacrolimus was low early after Tx (eg, median 78.6 around day 4) and variable in
      all 4 periods ranging from 3.8 to 267 MUg h/L, whereas the predose concentrations
      (C0) were 0.0-17.9 MUg/L. From periods I to IV, the tacrolimus dose was doubled
      and the median dose per body weight-adjusted AUC(0-12 hours) increased by 123% (P
      = 0.017). The AUC(0-12 hours) of MPA was in the range 8.6-57.4 mg h/L, with
      median values from 21.9 to 27.8 mg h/L, whereas C0 was between 0.0 and 7.3 mg/L
      in the 4 periods (medians from 1.2 to 1.6 mg/L). The maximum inhibition of
      inosine monophosphate dehydrogenase within a dose interval ranged from 9.5% to
      100%. CONCLUSIONS: This study confirmed the large variability in the PKs of
      tacrolimus and MPA in liver transplant recipients. In particular, the MPA AUC(0
      12 hours) was consistently low in all 4 periods. We also observed a low
      tacrolimus exposure during the first days after transplant compared with the
      following weeks.

PMID- 24081207
TI  - Population pharmacokinetic analysis of tacrolimus early after pediatric liver
      transplantation.
AB  - BACKGROUND: Tacrolimus (TAC) pharmacokinetics (PKs) show considerable unexplained
      variability, particularly in the early period after transplantation. Therefore,
      TAC is a good candidate for therapeutic drug monitoring. The main objective of
      the present work was to propose a robust PK model for TAC in the early period
      after transplantation, with the final goal to provide practitioners with a tool
      for dose individualization in pediatric patients. METHODS: TAC concentration data
      were obtained from 82 pediatric liver allograft recipients during the first 2
      weeks after transplantation. Previously published models, and a model recently
      developed by our group for pediatrics early after pediatric liver
      transplantation, were fitted to the data and their predictive performance
      compared with the performances of a model developed using the data from 82
      pediatric patients. RESULTS: During the data-driven analysis, the PKs of TAC were
      best described by a 1-compartment model with time-varying first order
      elimination. Apparent volume of distribution and blood clearance estimates were
      283 L and 10 L/h, respectively. The absorption was also considered to be a first
      order process, with a first order rate fixed to 4.45 hours. Parameters were
      estimated with good precision and accuracy. Although hematocrit levels, time
      after transplantation, liver weight, and body weight influenced the clearance,
      body weight was the only covariate retained on volume of central and peripheral
      compartments. Two of the 5 previous models showed acceptable predictive
      performances using the observed data. CONCLUSIONS: Time after transplantation,
      body weight, and hematocrit levels were shown to influence TAC PK in the early
      pediatric post-liver transplantation period and should be considered, besides
      therapeutic drug monitoring, by clinicians for the TAC posology prescription and
      adaptation.

PMID- 24081212
TI  - Tris-ACE-alpha-cyclodextrin tripods: chemistry and metal coordination behaviour.
AB  - The synthesis of C3-symmetrical tris-(ACE)-(6,6'-bis-heterocyclyl)-alpha
      cyclodextrins via"one pot" Staudinger-Aza-Wittig (SAW) reaction is described. The
      spectroscopic properties of their metal coordination compounds were analysed. The
      spontaneous formation of metallosupramolecular helicates generate strong exciton
      coupling features enlighten much information on the nature, the geometries of the
      complexes and their absolute configuration. 

PMID- 24081208
TI  - Limited sampling model for advanced mycophenolic acid therapeutic drug monitoring
      after liver transplantation.
AB  - BACKGROUND: The immunosuppressive drug mycophenolate mofetil (MMF), with
      mycophenolic acid (MPA) as active metabolite, is a nonnephrotoxic alternative to
      calcineurin inhibitors. Therapeutic drug monitoring (TDM) of MPA may improve
      clinical benefit from MMF therapy, especially in MMF monotherapy or with reduced
      dose of a calcineurin inhibitor. Limited data are available on TDM strategies for
      MPA in orthotopic liver transplantation (OLT). The authors here describe the
      pharmacokinetic (PK) behavior of MPA after OLT and developed a Bayesian limited
      sampling model for monitoring MMF after OLT. METHODS: PK data were obtained from
      57 stable patients, and trapezoidal area under the curve (AUC(0-12h)) was
      calculated. The effect of the covariates kidney function and serum albumin
      concentration was studied. A TDM strategy was developed based on individualized
      population PKs using Bayesian estimations and limited sampling models to predict
      the MPA AUC. RESULTS: A relationship between MMF dose and MPA AUC was found and a
      8-fold apparent clearance range of MPA was observed at the same dose level.
      Significant relationships of albumin concentration and creatinine clearance with
      MPA plasma clearance were identified (respectively, r2 = 0.12 and 0.24; P <
      0.05). A model with limited sampling at 0, 0.5, 1, 2, and 3 hours after drug
      administration showed very good correlation with trapezoidal AUC(0-12h) with
      acceptable bias and precision (r2 = 0.92, mean prediction error = 1, mean
      absolute prediction error = 13; P < 0.05). CONCLUSIONS: Remarkable variability of
      MPA clearance in stable OLT patients exists, which can be partially explained by
      the patients' albumin serum levels and creatinine clearance. Systemic exposure in
      these patients can be accurately assessed by the Bayesian limited sampling TDM
      strategy.

PMID- 24081213
TI  - Changes in psychotherapy utilization among veterans with depression, anxiety, and
      PTSD.
AB  - OBJECTIVE: Large-scale health care systems such as the Veterans Health
      Administration (VHA) have recently invested heavily in the expansion of
      psychotherapy services. This study examined longitudinal changes in use of
      psychotherapy at the VHA during a period of substantial programmatic change
      targeting increased availability and quality of mental health care. METHODS: This
      retrospective cohort study used data from the VHA National Patient Care Database
      outpatient treatment files to identify patients with a new-onset diagnosis of
      depression, anxiety, or posttraumatic stress disorder during fiscal years (FYs)
      2004 (N=424,428), 2007 (N=494,318), and 2010 (N=583,733). Use of psychotherapy
      during the 12 months after diagnosis was assessed. RESULTS: The proportion of
      patients receiving any psychotherapy increased across the three study time points
      (FY 2004, 21%; FY 2007, 22%; and FY 2010, 27%). Amount of psychotherapy also
      increased such that with time a growing proportion of patients received eight or
      more psychotherapy sessions. The median time between diagnosis and start of
      psychotherapy decreased from 56 to 47 days from FY 2004 to FY 2010. Consistent
      with VHA expansion efforts, more substantial increases in psychotherapy reach,
      amount, and timeliness occurred between FY 2007 and 2010 than between FY 2004 and
      FY 2007. CONCLUSIONS: These findings highlight recent increases in the use of VHA
      psychotherapy and correspond to substantial efforts to improve access to mental
      health services. Despite these advances, most newly diagnosed patients received
      no psychotherapy or a low-intensity amount of psychotherapy. Additional efforts
      to promote veteran engagement in needed mental health services appear warranted.

PMID- 24081214
TI  - Target vessel detection by epicardial ultrasound in off-pump coronary bypass
      surgery.
AB  - OBJECTIVE: The detection of embedded coronary arteries is difficult especially in
      off-pump coronary bypass surgery. From June 2010, we introduced high-frequency
      epicardial ultrasound (ECUS) to assess and evaluate embedded arteries during off
      pump coronary bypass surgery. METHODS: Between June 2010 and June 2011, a total
      of 89 consecutive patients underwent isolated coronary bypass surgery at our
      institution. The patients consisted of 72 men and 17 women with a mean age of
      67.9 years. We routinely use the VeriQC system (MediStim, Oslo, Norway) to detect
      the target vessels in the operation. The patients were assigned to one of two
      groups, depending on whether ECUS was used in the operation (n = 10, ECUS group)
      or not (n = 79, non-ECUS group). We analyzed the impact of introducing the ECUS
      in terms of operative outcome. RESULTS: All patients underwent revascularization
      using the off-pump technique without emergent conversion to cardiopulmonary
      bypass during surgery. The total number of distal anastomoses was 299, and 12
      target vessels could not be identified either visually or on palpation. Thus, the
      frequency of the embedded coronary arteries was 4.01% (12/299 cases). The
      preoperative profiles of the two groups were not significantly different.
      Operation time was significantly longer in the ECUS group (P = 0.02). There were
      no significant differences in postoperative outcome between the two groups.
      CONCLUSIONS: In the present study, in which the target coronary arteries could
      not be detected either visually or on palpation in 12 (4.01%) of 299 cases, the
      use of high-frequency ECUS allowed all patients to undergo off-pump coronary
      bypass surgery without conversion to cardiopulmonary bypass during the operation.
      High-frequency ECUS is therefore useful in off-pump coronary bypass surgery.

PMID- 24081215
TI  - Diagnostic efficacy of PET and PET/CT for recurrent lung cancer: a meta-analysis.
AB  - BACKGROUND: Lung cancer is one of the most common malignant tumors in the world,
      and is the leading cause of cancer-related mortality. Although there are no
      conclusive data to support the survival benefits of early detection or early
      treatment for recurrence, an early and accurate diagnosis of recurrence is
      critical to optimize therapy. PURPOSE: To compare the diagnostic value of
      positron emission tomography (PET) and positron emission tomography/computed
      tomography (PET/CT) using fluorine-18 deoxyglucose (18FDG) with conventional
      imaging techniques (CITs) for the detection of lung cancer recurrence. MATERIAL
      AND METHODS: A meta-analysis was performed, with systematic searches conducted
      using PubMed and EMBASE databases (up to 31 December 2011). Pooled sensitivity,
      specificity, and diagnostic odds ratio (DOR) values were calculated for 1035
      patients reported in 13 articles. Summary receiver-operating characteristic
      curves (SROC) were also generated. RESULTS: The pooled sensitivity (95% CI) for
      PET, PET/CT, and CITs were 0.94 (0.91-0.97), 0.90 (0.84-0.95), and 0.78 (0.71
      0.84), respectively. The pooled specificity (95% CI) for PET, PET/CT, and CITs
      were 0.84 (0.77-0.89), 0.90 (0.87-0.93), and 0.80 (0.75-0.84), respectively.
      Regarding sensitivity, lower values were associated with CITs than PET (P =
      0.000) and PET/CT (P = 0.005), and there was no significant difference between
      PET/CT and PET (P = 0.102). Regarding specificity, values for PET/CT and PET were
      significantly higher than for CITs (both P = 0.000), and there was no significant
      difference between PET/CT and PET (P = 0.273). In the SROC curves, a better
      diagnostic accuracy was associated with PET/CT than PET and CITs. CONCLUSION:
      PET/CT and PET were found to be superior modalities for the detection of
      recurrent lung cancer, and PET/CT was superior to PET.

PMID- 24081216
TI  - Structural evaluation of GM1-related carbohydrate-cholera toxin interactions
      through surface plasmon resonance kinetic analysis.
AB  - Surface plasmon resonance (SPR) can provide kinetic information about an
      interaction, and it can also be used to rapidly monitor dynamic processes, such
      as adsorption and degradation, without the need for sample labeling. Here, we
      employed SPR to analyze carbohydrate-protein interactions, particularly GM1
      related carbohydrate-Vibrio cholera toxin interactions. The interaction between
      cholera toxin subunits A (ctxA) and B (ctxB) was similar to general ligand
      receptor interactions. After the direct immobilization of thiol-containing GM1
      pentasaccharide on a gold surface, the GM1-ctxB interaction kinetics were
      evaluated, and they showed a similar degree of kinetics as reported in previous
      reports. We found that ctxA had a high affinity for the GM1-ctxAB complex,
      although its equilibrium dissociation constant was 10 times lower than that of
      GM1-ctxB binding. Comparative analyses of GM1-related carbohydrate-ctxAB
      interactions were also conducted to determine the kinetic values of several GM1
      analogues with different structures, although their kinetic values were one order
      of magnitude lower than those of the GM1-ctxAB interaction. The kinetic analysis
      results for the interactions of GM1 analogues and ctxAB indicated that the sialic
      acid thumb is important for recognition, and the terminal galactose and N
      acetylgalactosamine fingers are required to stabilize the GM1-ctxAB interaction.
      Taken together, our results indicate that the direct immobilization of
      carbohydrate in an SPR-based analytical system can be used to evaluate the
      structural contribution of carbohydrate moieties in carbohydrate-protein
      interactions, as well as provide valuable information that can be used to
      understand the interactions. 

PMID- 24081217
TI  - Beneficial effects of vildagliptin on retinal injury in obese type 2 diabetic
      rats.
AB  - BACKGROUND/AIMS: Vildagliptin is an oral inhibitor of dipeptidyl peptidase-4, an
      enzyme mainly responsible for inactivating incretins, and one of the widely used
      drugs for the treatment of type 2 diabetes. However, effects of vildagliptin on
      retinal injury in diabetes remain unclear. We examined here whether oral
      administration of vildagliptin inhibited gene expression of inflammatory and
      thrombogenic parameters in Otsuka Long-Evans Tokushima Fatty rats (OLETF rats),
      an animal model of obese type 2 diabetes. METHODS: OLETF rats at 22 weeks of age
      were given vehicle or 3 mg/kg of vildagliptin for another 10 weeks. Gene
      expression was analyzed in quantitative real-time reverse transcription
      polymerase chain reaction. RESULTS: Vildagliptin significantly inhibited the
      increase in body weight and decreased average fasting blood glucose in the OLETF
      rats. Compared with 22-week-old OLETF rats, gene expression levels of vascular
      endothelial growth factor, intercellular adhesion molecule-1, plasminogen
      activator inhibitor-1 and pigment epithelium-derived factor were significantly
      increased in the retinas of OLETF rats at 32 weeks of age, all of which were
      inhibited by treatment with vildagliptin. CONCLUSIONS: The present study
      demonstrated for the first time that vildagliptin inhibited inflammatory and
      thrombogenic reactions in the retinas of obese type 2 diabetic rats. Vildagliptin
      may play a protective role against diabetic retinopathy.

PMID- 24081218
TI  - Tailoring antiplatelet therapy in acute coronary syndromes: the thin red line.

PMID- 24081219
TI  - Preoperative chest x-rays: a teachable moment.

PMID- 24081220
TI  - Clofarabine-induced kidney toxicity.
AB  - Clofarabine is a purine nucleoside analog indicated for treatment of relapsed or
      refractory acute lymphoblastic leukaemia in children. The drug is also
      increasingly used, outside of its FDA approved indication, for treatment of
      relapsed or refractory acute myeloid leukemia in adults. It acts by inhibiting
      DNA synthesis, the enzyme ribonucleotide reductase and repair and activation of
      mitochondrial repair processes. We describe a case of a 48-year-old male with
      refractory acute myeloid leukemia with acute kidney injury associated with
      clofarabine treatment. We conducted a review of the literature and utilized the
      Food and Drug Administration Adverse Event Reporting System to identify
      spontaneous reporting of renal adverse events with this drug in 29 other cases.
      Since clofarabine inhibits ribonucleotide reductase, we postulate by
      extrapolation from the animal studies that collapsing glomerulopathy or severe
      tubular injury or a combination of both may be the mechanism of acute kidney
      injury observed with this agent. This would be consistent with the observed
      severe acute kidney injury and proteinuria in humans. 

PMID- 24081221
TI  - Insights about health-related quality of life in cancer patients indicate demands
      for better pharmaceutical care.
AB  - OBJECTIVES: To highlight the health-related quality of life scale scores for
      Saudi patients with different types of cancer, to get understanding and
      foundation for improvements. To suggest suitable plans for quality of life
      improvement based on study outcome. The role of oncology pharmacy will be
      stressed. METHODS: A cross-sectional descriptive study was conducted at a
      tertiary regional hospital using the European Organization for Research and
      Treatment of Cancer QLQ-C30 questionnaire. Attendees were patients diagnosed with
      any type of cancer and eligible for active anticancer treatment and/or palliative
      care. RESULTS: Quality of life was evaluated for 87 participants. Most of
      patients were aged between 51 and 60 years; and 50% had active treatment with
      chemotherapy. Patients seemed to perform well with respect to average scores in
      both the symptoms and the functional health status scales. The mean score for the
      global quality of life scale was 47.2 +/- 27.1, while the range of mean scores
      for the five function subscales was 59.0 +/- 27.1 to 81.6 +/- 13.8, indicating
      average level of general wellbeing with above average to high level of functional
      health status, while >50% of the patients met the operational criterion having
      less severe symptoms. Outpatients generally had somewhat higher scores as
      compared to hospitalized patients. CONCLUSION: The general quality of life seemed
      satisfactory, but there is still need to improve care. Based on results from
      other studies, oncology pharmacists' roles are essential to improve quality of
      life through treatment counseling, follow-up on drug support therapy, stress on
      patient's education through specific programs, review and update the local
      guidelines, and conduct more research.

PMID- 24081222
TI  - Functional analysis of seven genes linked to body mass index and adiposity by
      genome-wide association studies: a review.
AB  - Genome-wide association studies (GWAS) have identified a total of about 40 single
      nucleotide polymorphisms (SNPs) that show significant linkage to body mass index,
      a widely utilised surrogate measure of adiposity. However, only 8 of these
      associations have been confirmed by follow-up GWAS using more sophisticated
      measures of adiposity (computed tomography). Among these 8, there is a SNP close
      to the gene FTO which has been the subject of considerable work to diagnose its
      function. The remaining 7 SNPs are adjacent to, or within, the genes NEGR1,
      TMEM18, ETV5, FLJ35779, LINGO2, SH2B1 and GIPR, most of which are less well
      studied than FTO, particularly in the context of obesity. This article reviews
      the available data on the functions of these genes, including information gleaned
      from studies in humans and animal models. At present, we have virtually no
      information on the putative mechanism associating the genes FLJ35779 and LINGO2
      to obesity. All of these genes are expressed in the brain, and for 2 of them
      (SH2B1 and GIPR), a direct link to the appetite regulation system is known. SH2B1
      is an enhancer of intracellular signalling in the JAK-STAT pathway, and GIPR is
      the receptor for an appetite-linked hormone (GIP) produced by the alimentary
      tract. NEGR1, ETV5 and SH2B1 all have suggested roles in neurite outgrowth, and
      hence SNPs adjacent to these genes may affect development of the energy balance
      circuitry. Although the genes have central patterns of gene expression, implying
      a central neuronal connection to energy balance, for at least 4 of them (NEGR1,
      TMEM18, SH2B1 and GIPR), there are also significant peripheral functions related
      to adipose tissue biology. These functions may contribute to their effects on the
      obese phenotype.

PMID- 24081223
TI  - Genetics of food intake self-regulation in childhood: literature review and
      research opportunities.
AB  - Pediatric obesity results from a daily energy imbalance between intake and
      expenditure, an imbalance potentially as slight as ~30-50 kcal/day (e.g., a few
      extra sips of cola or bites of a cookie). That an 'energy gap' so small may be so
      powerful suggests the importance of understanding mechanisms of food intake self
      regulation (FISR). This review focuses on 4 behavioral indices of FISR in
      childhood: (1) eating in the absence of hunger; (2) eating rate; (3) caloric
      compensation and satiety responsiveness, and (4) food responsiveness. Evidence
      from pediatric samples around the world indicates that these traits are
      associated with body mass index, are heritable, and are linked to polymorphisms
      in the FTO gene. We review these data, also discussing their relevance to
      practical issues of parental feeding styles, portion sizes, and health literacy
      and numeracy. Research gaps and opportunities for future investigation are
      discussed. Multidisciplinary approaches and study designs that can address gene
      environment interactions are needed to advance the science of FISR and stimulate
      new avenues for childhood obesity prevention.

PMID- 24081224
TI  - Epigenetics and obesity: a relationship waiting to be explained.
AB  - Obesity can have multifactorial causes that may change with development and are
      not simply attributable to one's genetic constitution. To date, expensive and
      laborious genome-wide association studies have only ascribed a small contribution
      of genetic variants to obesity. The emergence of the field of epigenetics now
      offers a new paradigm with which to study excess fat mass. Currently, however,
      there are no compelling epigenetic studies to explain the role of epigenetics in
      obesity, especially from a developmental perspective. It is clear that until
      there are advances in the understanding of the main mechanisms by which different
      fat types, i.e. brown, beige, and white, are established and how these differ
      between depots and species, population-based studies designed to determine
      specific aspects of epigenetics will be potentially limited. Obesity is a slowly
      evolving condition that is not simply explained by changes in the intake of one
      macronutrient. The latest advances in epigenetics, coupled with the establishment
      of relevant longitudinal models of obesity, which incorporate functionally
      relevant end points, may now permit the precise contribution of epigenetic
      modifications to excess fat mass to be effectively studied.

PMID- 24081226
TI  - Gene * environment interactions in obesity: the state of the evidence.
AB  - BACKGROUND/AIMS: Obesity is a pervasive and highly prevalent disease that poses
      substantial health risks to those it affects. The rapid emergence of obesity as a
      global epidemic and the patterns and distributions of the condition within and
      between populations suggest that interactions between inherited biological
      factors (e.g. genes) and relevant environmental factors (e.g. diet and physical
      activity) may underlie the current obesity epidemic. METHODS: We discuss the
      rationale for the assertion that gene * lifestyle interactions cause obesity,
      systematically appraise relevant literature, and consider knowledge gaps future
      studies might seek to bridge. RESULTS: We identified >200 relevant studies, of
      which most are relatively small scale and few provide replication data.
      CONCLUSION: Although studies on gene * lifestyle interactions in obesity point
      toward the presence of such interactions, improved data standardization,
      appropriate pooling of data and resources, innovative study designs, and the
      application of powerful statistical methods will be required if translatable
      examples of gene * lifestyle interactions in obesity are to be identified. Future
      studies, of which most will be observational, should ideally be accompanied by
      appropriate replication data and, where possible, by analogous findings from
      experimental settings where clinically relevant traits (e.g. weight regain and
      weight cycling) are outcomes.

PMID- 24081225
TI  - Genetic admixture and obesity: recent perspectives and future applications.
AB  - The process of the colonization of the New World that occurred centuries ago
      served as a natural experiment, creating unique combinations of genetic material
      in newly formed admixed populations. Through a genetic admixture approach, the
      identification and genotyping of ancestry informative markers have allowed for
      the estimation of proportions of ancestral parental populations among individuals
      in a sample. These admixture estimates have been used in different ways to
      understand the genetic contributions to individual variation in obesity and body
      composition parameters, particularly among diverse admixed groups known to differ
      in obesity prevalence within the United States. Although progress has been made
      through the use of genetic admixture approaches, further investigations are
      needed in order to explore the interaction of environmental factors with the
      degree of genetic ancestry in individuals. A challenge to confront at this time
      would be to further stratify and define environments in progressively more
      granular terms, including nutrients, muscle biology, stress responses at the
      cellular level, and the social and built environments.

PMID- 24081227
TI  - Interface between pharmacotherapy and genes in human obesity.
AB  - Obesity is a polygenic chronic condition, and dysregulation in multiple
      underlying energy balance processes drives the obese phenotype. Lifestyle changes
      can be difficult to sustain long term, and anti-obesity drugs can be an
      advantageous component of a successful weight loss plan. However, due to lack of
      efficacy or adverse safety profiles, there is currently a limited selection of
      anti-obesity drugs on the market. This, coupled with the notable interindividual
      variability in efficacy of approved treatments, represents a significant unmet
      medical need. In this review, we will highlight this variability in weight loss
      response to these existing anti-obesity compounds and discuss how underpinning
      genetic variation is associated with weight loss outcomes. Existing research in
      the field of pharmacogenomics and obesity drugs will be highlighted, as will
      possibilities for future focus. We will conclude by exploring examples of
      successful pharmacogenomics studies, and also by asking how pharmacogenomics can
      be built into the drug development pipeline for the benefit of patients and
      pharmaceutical companies alike.

PMID- 24081228
TI  - Estimating the range of obesity treatment response variability in humans: methods
      and illustrations.
AB  - BACKGROUND/AIMS: The rising prevalence of human obesity worldwide has focused
      research on a variety of interventions that result in highly varied degrees of
      weight loss (WL). The advent of genomic testing has quantified estimates of both
      the contribution of genetic factors to the development of obesity as well as
      racial/ethnic variation of risk alleles across subpopulations. More recent
      studies have examined genetic associations with effectiveness of WL
      interventions, but to date are unable to explain a large proportion of the
      variance observed. METHODS: We describe and provide two illustrations of
      statistical methods to estimate upper and lower bounds of WL treatment response
      heterogeneity (TRH) in the absence of genotypic data, using published summary
      statistics and a raw data set from WL studies. RESULTS: Thirty-two studies had
      some evidence of a positive mean treatment effect with respect to the control
      intervention. Twelve of these 32 studies reported WL TRH. Of these 12, 3
      demonstrated an estimated proportion of >5% of the sampled population having an
      outcome opposite the mean effect. In the raw data set, bounds estimations for
      change in waist circumference revealed tighter ranges in men than women.
      CONCLUSION: Future studies may be able to take advantage of multiple approaches,
      including the method we describe, to identify and quantify the presence of TRH in
      studies of WL or related outcomes.

PMID- 24081229
TI  - Identification of pleiotropic genetic effects on obesity and brain anatomy.
AB  - BACKGROUND/AIMS: Obesity is a major contributor to the global burden of chronic
      disease and disability, though current knowledge of causal biologic underpinnings
      is lacking. Through the regulation of energy homeostasis and interactions with
      adiposity and gut signals, the brain is thought to play a significant role in the
      development of this disorder. While neuroanatomical variation has been associated
      with obesity, it is unclear if this relationship is influenced by common genetic
      mechanisms. In this study, we sought genetic components that influence both brain
      anatomy and body mass index (BMI) to provide further insight into the role of the
      brain in energy homeostasis and obesity. METHODS: MRI images of brain anatomy
      were acquired in 839 Mexican American individuals from large extended pedigrees.
      Bivariate linkage and quantitative analyses were performed in SOLAR. RESULTS:
      Genetic factors associated with an increased BMI were also associated with a
      reduced cortical surface area and subcortical volume. We identified two genome
      wide quantitative trait loci that influenced BMI and the ventral diencephalon
      volume, and BMI and the supramarginal gyrus surface area, respectively.
      CONCLUSIONS: This study represents the first genetic analysis seeking evidence of
      pleiotropic effects acting on both brain anatomy and BMI. Our results suggest
      that a region on chromosome 17 contributes to the development of obesity,
      potentially through leptin-induced signaling in the hypothalamus, and that a
      region on chromosome 3 appears to jointly influence the food-related reward
      circuitry and the supramarginal gyrus.

PMID- 24081230
TI  - Next-generation sequence analysis of genes associated with obesity and
      nonalcoholic fatty liver disease-related cirrhosis in extreme obesity.
AB  - OBJECTIVES: Genome-wide association studies (GWAS) have led to the identification
      of single nucleotide polymorphisms in or near several loci that are associated
      with the risk of obesity and nonalcoholic fatty liver disease (NAFLD). We
      hypothesized that missense variants in GWAS and related candidate genes may
      underlie cases of extreme obesity and NAFLD-related cirrhosis, an extreme
      manifestation of NAFLD. METHODS: We performed whole-exome sequencing on 6
      Caucasian patients with extreme obesity [mean body mass index (BMI) 84.4] and 4
      obese Caucasian patients (mean BMI 57.0) with NAFLD-related cirrhosis. RESULTS:
      Sequence analysis was performed on 24 replicated GWAS and selected candidate
      obesity genes and 5 loci associated with NAFLD. No missense variants were
      identified in 19 of the 29 genes analyzed, although all patients carried at least
      2 missense variants in the remaining genes without excess homozygosity. One
      patient with extreme obesity carried 2 novel damaging mutations in BBS1 and was
      homozygous for benign and damaging MC3R variants. In addition, 1 patient with
      NAFLD-related cirrhosis was compound heterozygous for rare damaging mutations in
      PNPLA3. CONCLUSIONS: These results indicate that analyzing candidate loci
      previously identified by GWAS analyses using whole-exome sequencing is an
      effective strategy to identify potentially causative missense variants underlying
      extreme obesity and NAFLD-related cirrhosis.

PMID- 24081231
TI  - Individual genetic variations related to satiety and appetite control increase
      risk of obesity in preschool-age children in the STRONG kids program.
AB  - BACKGROUND/AIMS: The burden of the childhood obesity epidemic is well recognized;
      nevertheless, the genetic markers and gene-environment interactions associated
      with the development of common obesity are still unknown. In this study,
      candidate genes associated to satiety and appetite control pathways with obesity
      related traits were tested in Caucasian preschoolers from the STRONG Kids
      project. METHODS: Eight genetic variants in genes related to obesity (BDNF, LEPR,
      FTO, PCSK1, POMC, TUB, LEP, and MC4R) were genotyped in 128 children from the
      STRONG Kids project (mean age 39.7 months). Data were analyzed for individual
      associations and to test for genetic predisposition scores (GPSs) with body mass
      index (BMI) and anthropometric traits (Z-scores, e.g. height-for-age Z-score,
      HAZ). Covariates included age, sex, and breastfeeding (BF) duration. RESULTS:
      Obesity and overweight prevalence was 6.3 and 19.5%, respectively, according to
      age- and sex-specific BMI percentiles. Individual genetic associations of MC4R
      and LEPR markers with HAZ were strengthened when BF duration was included as a
      covariate. Our GPSs show that, as the number of risk alleles increased, the risk
      of higher BMI and HAZ also increased. Overall, the GPSs assembled were able to
      explain 2-3% of the variability in BMI and HAZ phenotypes. CONCLUSION: Genetic
      associations with common obesity-related phenotypes were found in the STRONG Kids
      project. GPSs assembled for specific candidate genes were associated with BMI and
      HAZ phenotypes.

PMID- 24081234
TI  - Impact of informing overweight individuals about the role of genetics in obesity:
      an online experimental study.
AB  - BACKGROUND/AIMS: Increasing public awareness of obesity genetics could have
      beneficial or harmful effects on overweight individuals. This study examined the
      impact of genetic information on weight-related cognitions as well as interest in
      personalized genetic information about obesity among overweight individuals.
      METHODS: Online survey respondents (n = 655) were randomly assigned to read
      either genetic, gene-environment, or nongenetic obesity causal information. Fifty
      two percent of the participants were female, 82.4% were White, 45% had an annual
      income of USD <40,000, and the mean BMI was 32.5. Internalized weight stigma was
      measured using the Weight Bias Internalization Scale. RESULTS: Participants in
      the genetic and gene-environment conditions were more likely to believe genetics
      increase obesity risk than participants in the nongenetic condition (both p <
      0.05); however, they did not differ regarding internalized weight stigma. Sixty
      four percent of the participants expressed interest in receiving personalized
      genetic information about their obesity risk. CONCLUSION: Dissemination of
      information about obesity genetics may have neither a beneficial nor a harmful
      impact on how overweight individuals perceive themselves. Some overweight
      individuals may be interested in receiving personalized genetic information. The
      actual effects of obesity genetic information being incorporated into public
      health messages and of personalized genetic information on obesity prevention and
      treatment interventions remain to be seen.

PMID- 24081233
TI  - The positive association of obesity variants with adulthood adiposity strengthens
      over an 80-year period: a gene-by-birth year interaction.
AB  - OBJECTIVE: To test the hypothesis that the statistical effect of obesity-related
      genetic variants on adulthood adiposity traits depends on birth year. METHODS:
      The study sample included 907 related, non-Hispanic White participants in the
      Fels Longitudinal Study, born between 1901 and 1986, and aged 25-64.99 years (474
      females; 433 males) at the time of measurement. All had both genotype data from
      which a genetic risk score (GRS) composed of 32 well-replicated obesity-related
      common single nucleotide polymorphisms was created, and phenotype data [including
      body mass index (BMI), waist circumference, and the sum of four subcutaneous
      skinfolds]. Maximum likelihood-based variance components analysis was used to
      estimate trait heritabilities, main effects of GRS and birth year, GRS-by-birth
      year interaction, sex, and age. RESULTS: Positive GRS-by-birth year interaction
      effects were found for BMI (p < 0.001), waist circumference (p = 0.007), and
      skinfold thickness (p < 0.007). For example, each one-allele increase in GRS was
      estimated to result in a 0.16 increase in BMI among males born in 1930 compared
      to a 0.47 increase among those born in 1970. CONCLUSIONS: These novel findings
      suggest the influence of common obesity susceptibility variants has increased
      during the obesity epidemic.

PMID- 24081237
TI  - Determination of absolute configuration of the phosphonic acid moiety of
      fosfazinomycins.
AB  - Fosfazinomycins A and B produced by Streptomyces lavendofoliae share the same
      phosphonate moiety with one chiral centre of unknown configuration which was
      determined by synthesising both enantiomers of 2-hydroxy-2-phosphonoacetic acid
      methyl ester. A chiral cyclic phosphite was reacted with methyl glyoxylate in a
      Pudovik reaction to give a pair of diastereomeric alpha-hydroxyphosphonates,
      which were separated by HPLC. The configurations at C-2 were assigned on the
      basis of single crystal X-ray structure analysis. Deprotection of these
      diastereomers furnished the enantiomeric alpha-hydroxyphosphonic acids, of which
      the (S)-configured had the same sign of optical rotation as the phosphonic acid
      moiety of the two fosfazinomycins. 

PMID- 24081236
TI  - TFAP2B -dietary protein and glycemic index interactions and weight maintenance
      after weight loss in the DiOGenes trial.
AB  - BACKGROUND: TFAP2B rs987237 is associated with obesity and has shown interaction
      with the dietary fat-to-carbohydrate ratio, which has an effect on weight loss.
      We investigated interactions between rs987237 and protein-to-carbohydrate ratio
      or glycemic index (GI) in relation to weight maintenance after weight loss.
      METHODS: This study included 742 obese individuals from 8 European countries who
      participated in the Diet, Obesity, and Genes (DiOGenes) trial, lost >= 8% of
      their initial body weight during an 8-week low-calorie diet and were randomized
      to one of 5 ad libitum diets with a fixed energy percentage from fat: either low
      protein/low-GI, low-protein/high-GI, high-protein/low-GI, or high-protein/high-GI
      diets, or a control diet for a 6-month weight maintenance period. Using linear
      regression analyses and additive genetic models, we investigated main and dietary
      interaction effects of TFAP2B rs987237 in relation to weight maintenance.
      RESULTS: In total, 468 completers of the trial were genotyped for rs987237. High
      protein diets were beneficial for weight maintenance in the AA genotype group
      (67% of participants), but in the AG and GG groups no differences were observed
      for low- or high-protein diets. On the high-protein diet, carriers of the obesity
      risk allele (G allele) regained 1.84 kg (95% CI: 0.02; 3.67, p = 0.047) more body
      weight per risk allele than individuals on a low-protein diet. There was no
      interaction effect between rs987237 and GI on weight maintenance. CONCLUSION:
      TFAP2B rs987237 and dietary protein/carbohydrate interacted to modify weight
      maintenance. Considering the carbohydrate proportion of the diet, the interaction
      was different from the previously reported rs987237-fat-to-carbohydrate ratio
      interaction for weight loss. Thus, TFAP2B-macronutrient interactions might
      diverge depending on the nutritional state.

PMID- 24081235
TI  - Propagation of obesity across generations: the roles of differential realized
      fertility and assortative mating by body mass index.
AB  - BACKGROUND/AIMS: To quantify the extent to which the increase in obesity observed
      across recent generations of the American population is associated with the
      individual or combined effects of assortative mating (AM) for body mass index
      (BMI) and differential realized fertility by BMI. METHODS: A Monte Carlo
      framework is formed and informed using data collected from the National
      Longitudinal Survey of Youth (NLSY). The model has 2 portions: one that generates
      childbirth events on an annual basis and another that produces a BMI for each
      child. Once the model is informed using the data, a reference distribution of
      offspring BMIs is simulated. We quantify the effects of our factors of interest
      by removing them from the model and comparing the resulting offspring BMI
      distributions with that of the baseline scenario. RESULTS: An association between
      maternal BMI and number of offspring is evidenced in the NLSY data as well as the
      presence of AM. These 2 factors combined are associated with an increased mean
      BMI (+0.067, 95% CI: 0.056; 0.078), an increased BMI variance (+0.578, 95% CI:
      0.418; 0.736) and an increased prevalence of obesity (RR 1.032, 95% CI: 1.023;
      1.041) and BMIs >40 (RR 1.083, 95% CI: 1.053; 1.118) among offspring. CONCLUSION:
      Our investigation suggests that both differential realized fertility and AM by
      BMI appear to play a role in the increasing prevalence of obesity in America.

PMID- 24081238
TI  - Epidemiology of idiopathic pulmonary fibrosis in Europe--an update.
AB  - Idiopathic pulmonary fibrosis (IPF) is a non-neoplastic pulmonary disease that is
      characterised by the formation of scar tissue within the lungs in the absence of
      any known cause. IPF is the most common of the idiopathic interstitial pneumonias
      and is an important cause of respiratory mortality. IPF is a relatively rare
      disease with an estimated prevalence ranging from two to 29 cases per 100,000 and
      slightly higher in men (20.2/100,000) than in women (13.2/100,000). The mean age
      at presentation is 66 years. Little recent epidemiological data on the
      prevalence, incidence, risk factors, and mortality related to the disease are
      available or are limited by methodological weaknesses. Outstanding questions
      remain, including the causes of IPF, why the incidence is on the rise, and how
      best to manage this disease. New comparable epidemiological data on IPF are
      needed. 

PMID- 24081239
TI  - Classification, natural history and staging of idiopathic pulmonary fibrosis.
AB  - Idiopathic pulmonary fibrosis (IPF) is defined as a fibrosing disease limited to
      the lungs of unknown aetiology characterised radiologically and/or
      morphologically by the usual interstitial pneumonitis pattern. It is a disease
      with an ominous prognosis. There is currently no consensus regarding the staging
      and classification of IPF. As highlighted in the revised ATS/ERS guidelines,
      proposed stages may be based on resting pulmonary function test measurements
      and/or the extent of radiologic abnormalities, but it is unknown if these staging
      approaches are relevant to clinical decision-making. Thus, the unmet needs in IPF
      include a complete knowledge of the pathogenetic mechanisms leading to lung
      destruction, an improved understanding of different clinico-radiological subtypes
      of this disorder and finally, the identification of staging systems of clinical
      value. 

PMID- 24081240
TI  - Inflammation and dysregulated fibroblast proliferation--new mechanisms?
AB  - Idiopathic pulmonary fibrosis (IPF) is a devastating, age-related lung disease of
      unknown cause that has few treatment options. Once thought to be a chronic
      inflammatory process, current evidence indicates that the fibrotic response may
      primarily be driven by abnormally activated alveolar epithelial cells and the
      underlying mesenchyme. The mediators produced and present in this
      microenvironment induce the formation of fibroblast foci through the
      proliferation of resident mesenchymal cells, attraction of circulating
      fibrocytes, and stimulation of epithelial to mesenchymal transition. The
      fibroblast and myofibroblast foci secrete excessive amounts of extracellular
      matrix, mainly collagens, resulting in scarring and destruction of the lung
      architecture. The detailed mechanisms that link IPF with ageing and aberrant
      epithelial activation are unknown, but some evidence suggests that the abnormal
      recapitulation of developmental pathways and epigenetic changes may play a role.
      This review provides a brief synopsis of highlights in the current understanding
      of the pathophysiology of IPF, as well as novel therapeutics being explored in
      clinical trials for the treatment of this devastating disease. 

PMID- 24081241
TI  - Molecular biomarkers in idiopathic pulmonary fibrosis and disease severity.
AB  - Despite major accomplishments in our understanding of idiopathic pulmonary
      fibrosis (IPF), its diagnosis, and management continues to pose significant
      challenges. The clinical management of IPF remains a major challenge due to a
      limited number of effective drug therapies, as well as accurate indicators of
      disease progression. Most patients die within at least five years after
      diagnosis. The identification of more accurate predictors of prognosis and
      survival in IPF is critical for physicians and would be useful to facilitate
      counselling of patients and their families, to aid communication among providers,
      and to guide optimal timing of transplantation. Improvements in molecular
      techniques have developed our understanding of IPF and have led to the
      identification of new pathways and a more targeted approach to the treatment of
      IPF with potentially novel anti-fibrotic agents. These insights have led to an
      increased interest in biomarkers of IPF disease progression. Although there are
      no validated biomarkers that are currently available, the need for surrogates of
      diagnosis, prognosis, and monitoring of disease course is great. However, there
      is currently no established method of combining these predictors to accurately
      determine prognosis or define disease stage. 

PMID- 24081242
TI  - Management of idiopathic pulmonary fibrosis and pulmonary hypertension.
AB  - Idiopathic pulmonary fibrosis (IPF) is an untreatable diffuse parenchymal lung
      disease with a median survival of approximately three years. Pulmonary
      hypertension (PH) is frequently seen in patients with IPF and is commonly
      attributed to hypoxic vasoconstriction and capillary destruction. Pathology
      findings include endothelial proliferation and medial hypertrophy that exceed
      those expected in the setting of hypoxia. Non-invasive evaluation has limited
      sensitivity and specificity for the diagnosis of PH in IPF; therefore, right
      heart catheterisation remains the 'gold standard' diagnostic test. PH in patients
      with IPF is associated with decreased exercise capacity and worse survival. Given
      the grave consequences of this condition, treatment of PH could improve
      functional outcomes and survival. However, possible treatments such as long-term
      supplemental oxygen and targeted vascular therapy are either unstudied or remain
      unproven. 

PMID- 24081243
TI  - Gastro-oesophageal reflux and idiopathic pulmonary fibrosis.
AB  - Idiopathic pulmonary fibrosis (IPF) is the most common of the idiopathic
      interstitial pneumonias. There is evidence of an increased prevalence of acid
      gastro-oesophageal reflux disease (GERD) in patients with IPF. Recent articles
      have focused on the potential role of chronic silent microaspiration in the
      pathogenesis of IPF. Aspiration in defined as the inhalation of gastric content
      into the larynx and lower respiratory tract. The reported use of GERD medications
      is an independent predictor of longer survival time in patients with IPF. These
      findings further support the hypothesis that GERD and chronic micro-aspiration
      may play important roles in the pathobiology of IPF. 

PMID- 24081244
TI  - Pirfenidone treatment in a patient with IPF and possible initial hypersensitivity
      pulmonitis.
AB  - The diagnosis of idiopathic pulmonary fibrosis (IPF) requires exclusion of other
      known causes of interstitial lung disease (ILD) (e.g., domestic and occupational
      environmental exposures, systemic connective tissue disease, and drug toxicity),
      the presence of a 'usual interstitial pneumonia' (UIP) pattern on high resolution
      computed tomography (HRCT), and specific combinations of HRCT and histopathologic
      patterns in patients subjected to surgical lung biopsy (SLB). A clear diagnosis
      and early treatment with currently the only approved anti-fibrotic drug,
      pirfenidone, represents the standard of care for the treatment of mild-to
      moderate IPF. This case report describes a patient with possible initial
      hypersensitivity pneumonitis and subsequent diagnosis of IPF with late
      development of pulmonary hypertension, and who was a candidate for lung
      transplantation. The patient showed slow progression of IPF during pirfenidone
      treatment in the CAPACITY and RECAP studies. 

PMID- 24081245
TI  - Treatment switching in idiopathic pulmonary fibrosis: from triple therapy to
      enrollment into a clinical investigational drug trial.
AB  - A number of pharmacological agents have been the focus of clinical trials over
      the past years. Although no single pharmacological agent is recommended by
      current guidelines, preliminary negative findings regarding the safety of a
      triple therapy regimen consisting of prednisone, azathioprine and N
      acetylcysteine have raised the question of whether it is no longer a treatment
      option. More recent data have resulted in the approval of pirfenidone in Europe.
      Pirfenidone shows a favourable risk-benefit profile and a beneficial effect in
      reducing the decline in lung function in patients with IPF. This case study
      describes the diagnosis and initial treatment of a patient with IPF with triple
      therapy of prednisone, azathioprine and N-acetylcysteine (NAC) followed by
      inclusion into a double-blind, randomised, placebo-controlled study and
      subsequent open-label extension trial of pirfenidone in IPF. 

PMID- 24081246
TI  - Management of a patient with familial idiopathic pulmonary fibrosis.
AB  - Idiopathic pulmonary fibrosis (IPF), the most common subtype of idiopathic
      interstitial pneumonia, is a chronic progressive lung disease with a very high
      mortality. Usually diagnosis is established in adults older than 50 years and
      most cases are considered to be sporadic. Individuals with a familial form of IPF
      have at least one affected member in the same primary biological family and
      account for less than 5% of total patients. Sporadic and familial IPF are
      clinically and histologically indistinguishable from one another, although some
      familial forms appear to develop at an earlier age and exhibit different patterns
      of gene transcription. This case study describes the early clinical course of a
      patient diagnosed with a familial form of IPF. 

PMID- 24081247
TI  - Long-term management of IPF with pirfenidone - a clinical case study with 5 years
      follow-up.
AB  - Idiopathic pulmonary fibrosis (IPF) is a progressively fibrotic interstitial lung
      disease that is associated with a median survival of 2-5 years from initial
      diagnosis. To date, the search for an effective treatment has involved numerous
      clinical trials of investigational agents but without significant success.
      Nevertheless, research over the past 10 years has provided us with a wealth of
      information on its histopathology, diagnostic work-up, and a greater
      understanding of its pathophysiology. Specifically, IPF is no longer thought to
      be a predominantly pro-inflammatory disorder. Rather, the fibrosis in IPF is
      increasingly understood to be the result of a fibroproliferative and aberrant
      wound healing cascade. The development of therapeutic targets has therefore
      shifted in accordance with this paradigm change. Emerging clinical data from
      recently published and ongoing trials investigating new potential pharmacological
      agents should be considered in the routine clinical management of these patients.
      Based upon encouraging results from randomised-controlled trials showing a
      positive effect in slowing decline in pulmonary function and reducing disease
      progression, pirfenidone was approved in 2011 as the first treatment in patients
      with IPF. This case study describes the clinical course of a patient enrolled
      into the Phase III and open-label extension studies of pirfenidone. 

PMID- 24081248
TI  - The 2nd AIR meeting--the current context of European IPF research and management.

PMID- 24081249
TI  - The 2nd AIR meeting--Working together to translate idiopathic pulmonary fibrosis
      research into practice.

PMID- 24081232
TI  - Human cardiovascular disease IBC chip-wide association with weight loss and
      weight regain in the look AHEAD trial.
AB  - BACKGROUND/AIMS: The present study identified genetic predictors of weight change
      during behavioral weight loss treatment. METHODS: Participants were 3,899
      overweight/obese individuals with type 2 diabetes from Look AHEAD, a randomized
      controlled trial to determine the effects of intensive lifestyle intervention
      (ILI), including weight loss and physical activity, relative to diabetes support
      and education, on cardiovascular outcomes. Analyses focused on associations of
      single nucleotide polymorphisms (SNPs) on the Illumina CARe iSelect (IBC) chip
      (minor allele frequency >5%; n = 31,959) with weight change at year 1 and year 4,
      and weight regain at year 4, among individuals who lost >= 3% at year 1. RESULTS:
      Two novel regions of significant chip-wide association with year-1 weight loss in
      ILI were identified (p < 2.96E-06). ABCB11 rs484066 was associated with 1.16 kg
      higher weight per minor allele at year 1, whereas TNFRSF11A, or RANK, rs17069904
      was associated with 1.70 kg lower weight per allele at year 1. CONCLUSIONS: This
      study, the largest to date on genetic predictors of weight loss and regain,
      indicates that SNPs within ABCB11, related to bile salt transfer, and TNFRSF11A,
      implicated in adipose tissue physiology, predict the magnitude of weight loss
      during behavioral intervention. These results provide new insights into potential
      biological mechanisms and may ultimately inform weight loss treatment.

PMID- 24081250
TI  - Hetero-epitaxy of anisotropic polycaprolactone films for the guidance of smooth
      muscle cell growth.
AB  - An anisotropic biocompatible composite PCL-PTFE film was used to guide smooth
      muscle cell outgrowth along defined directions. 

PMID- 24081251
TI  - Clinical presentation and molecular identification of four uncommon alpha globin
      variants in Thailand. Initiation codon mutation of alpha2-globin Gene
      (HBA2:c.1delA), donor splice site mutation of alpha1-globin gene (IVSI-1,
      HBA1:c.95 + 1G>A), hemoglobin Queens Park/Chao Pra Ya (HBA1:c.98T>A) and
      hemoglobin Westmead (HBA2:c.369C>G).
AB  - Alpha thalassemia is the most common genetic disease in the world with the
      prevalence of carriers ranging from 5-50% in several populations. Coinheritance
      of two defective alpha-globin genes usually gives rise to a symptomatic
      condition, hemoglobin (Hb) H disease. Previously, it has been suggested from
      several studies in different populations that nondeletional Hb H disease (-
      /alpha(T)alpha or --/alphaalpha(T)) is generally more severe than the deletional
      type (--/-alpha). In this report, we describe four rare nondeletional alpha
      thalassemia mutations in Thai individuals, including initiation codon mutation
      (HBA2:c.1delA), donor splice site mutation (IVSI-1, HBA1:c.95 + 1G>A), Hb Queens
      Park (HBA1:c.98T>A) [alpha32(B13)Met>Lys], and Hb Westmead (HBA2:c.369C>G)
      [alpha122(H5)His>Gln]. Interactions of the first three mutations with the
      alpha(0)-thalassemia resulted in nondeletional Hb H disease; however, their
      clinical presentations were rather mild and some were detected accidentally. This
      suggests that a genotype-phenotype correlation of alpha-thalassemia syndrome
      might be more heterogeneous and so the type of mutation does not simply imply the
      prediction of the resulting phenotype. Our data will be of use in future genetic
      counseling of such conditions that are increasingly identified thanks to the
      improvement of molecular analysis in routine laboratories.

PMID- 24081253
TI  - Processing and properties of textured potassium strontium niobate (KSr2Nb5O15)
      ceramic fibers--effect of texture on the electrical properties.
AB  - Textured ceramic fibers were fabricated from the tungsten-bronze-type
      piezoelectric (KSr2Nb5O15) . Development of crystallographic texture was
      evaluated through rocking curve analysis and a texture with Lotgering factor of
      0.97 was achieved. 1-3 piezocomposites were prepared from the textured fibers and
      their electrical properties were evaluated. Highly enhanced properties that are 2
      to 3 times higher than the random case were observed with increasing texture
      fraction with P(r) and d33 reaching 20 MUC/cm(2) and 75 pC/N, respectively.

PMID- 24081252
TI  - Flexible over-moded resonators based on P(VDF-TrFE) thin films with very high
      temperature coefficient.
AB  - This work presents for the first time a flexible over-moded resonator (OMR) based
      on P(VDF-TrFE) thin films. The devices were manufactured on commercially
      available elastic substrate with inkjet-printed electrodes. The sensing copolymer
      films used in the devices were polarized by the corona method after electrode
      deposition. The main performance parameters of the component were then
      determined. The manufactured OMRs on P(VDF-TrFE) exhibited a linear variation of
      frequency versus temperature and a very large value of temperature coefficient of
      frequency (TCF ? 1600 ppm/ degrees C). These properties suggest a great potential
      for using such components as low-cost and high-precision temperature sensors. The
      electromechanical coupling coefficient and the quality factor of the resonator
      were also characterized versus temperature. 

PMID- 24081255
TI  - Ultrasound contrast imaging: influence of scatterer motion in multi-pulse
      techniques.
AB  - In ultrasound contrast imaging, many techniques based on multiple transmissions
      have been proposed to increase the contrast-to-tissue ratio (CTR). They are
      generally based on the response of static scatterers inside the imaged region.
      However, scatterer motion, for example in blood vessels, has an inevitable
      influence on multi-pulse techniques, which can either enhance or degrade the
      technique involved. This paper investigates the response of static nonlinear
      media insonated by multi-pulses with various phase shifts, and the influence of
      scatterer motion on multi-pulse techniques. Simulations and experimental results
      from a single bubble and clouds of bubbles show that the phase shift of the
      echoes backscattered from bubbles is dependent on the transmissions' phase shift,
      and that the bubble motion influences the efficiency of multi-pulse techniques:
      fundamental and second-harmonic amplitudes of the processed signal change
      periodically, exhibiting maximum or minimum values, according to scatterer
      motion. Furthermore, experimental results based on the second-harmonic inversion
      (SHI) technique reveal that bubble motion can be taken into account to regulate
      the pulse repetition frequency (PRF). With the optimal PRF, the CTR of SHI images
      can be improved by about 12 dB compared with second-harmonic images. 

PMID- 24081254
TI  - Evaluating the feasibility of acoustic radiation force impulse shear wave
      elasticity imaging of the uterine cervix with an intracavity array: a simulation
      study.
AB  - The uterine cervix softens, shortens, and dilates throughout pregnancy in
      response to progressive disorganization of its layered collagen microstructure.
      This process is an essential part of normal pregnancy, but premature changes are
      associated with preterm birth. Clinically, there are no reliable noninvasive
      methods to objectively measure cervical softening or assess cervical
      microstructure. The goal of these preliminary studies was to evaluate the
      feasibility of using an intracavity ultrasound array to generate acoustic
      radiation force impulse (ARFI) excitations in the uterine cervix through
      simulation, and to optimize the acoustic radiation force (ARF) excitation for
      shear wave elasticity imaging (SWEI) of the tissue stiffness. The cervix is a
      unique soft tissue target for SWEI because it has significantly greater acoustic
      attenuation (alpha = 1.3 to 2.0 dB.cm(-1).MHz(-)1) than other soft tissues, and
      the pathology being studied tends to lead to an increase in tissue compliance,
      with healthy cervix being relatively stiff compared with other soft tissues (E ~
      25 kPa). Additionally, the cervix can only be accessed in vivo using a
      transvaginal or catheter-based array, which places additional constraints on the
      excitation focal characteristics that can be used during SWEI. Finite element
      method (FEM) models of SWEI show that larger-aperture, catheter-based arrays can
      utilize excitation frequencies up to 7 MHz to generate adequate focal gain up to
      focal depths 10 to 15 mm deep, with higher frequencies suffering from excessive
      amounts of near-field acoustic attenuation. Using full-aperture excitations can
      yield ~40% increases in ARFI-induced displacements, but also restricts the depth
      of field of the excitation to ~0.5 mm, compared with 2 to 6 mm, which limits the
      range that can be used for shear wave characterization of the tissue. The center
      frequency content of the shear wave particle velocity profiles ranges from 1.5 to
      2.5 kHz, depending on the focal configuration and the stiffness of the material
      being imaged. Overall, SWEI is possible using catheter-based imaging arrays to
      generate adequate displacements in cervical tissue for shear wave imaging,
      although specific considerations must be made when optimizing these arrays for
      this shear wave imaging application.

PMID- 24081256
TI  - Finding the peak velocity in a flow from its Doppler spectrum.
AB  - The signal backscattered by blood cells crossing a sample volume produces a
      Doppler power spectrum determined by the scatterers? velocity distribution.
      Because of intrinsic spectral broadening, the peak Doppler frequency observed
      does not correspond to the peak velocity in the flow. Several methods have been
      proposed for estimating the maximum velocity component--an important clinical
      parameter--but these methods are approximate, based on heuristic thresholds that
      can be inaccurate and strongly affected by noise. Reported here is a method of
      modeling the Doppler power spectrum of a flow, and from that model, determining
      what Doppler frequency on the descending slope of the power spectrum corresponds
      to the peak velocity in the insonated flow. It is shown that, for a fully
      insonated flow with a parabolic velocity distribution, the peak velocity
      corresponds to the Doppler frequency at the half-power point on that slope. The
      method is demonstrated to be robust with regard to the effects of noise and valid
      for a wide range of acquisition parameters. Experimental maximum velocity
      measurements on steady flows with rates between 100 and 300 mL/min (peak velocity
      range 6.6 cm/s to 19.9 cm/s) show a mean bias error that is smaller than 1%.

PMID- 24081257
TI  - Model-based compressive sensing for damage localization in Lamb wave inspection.
AB  - Compressive sensing (CS) has emerged as a potentially viable technique for the
      efficient compression and analysis of high-resolution signals that have a sparse
      representation in a fixed basis. In this work, we have developed a CS approach
      for ultrasonic signal decomposition suitable to achieve high performance in Lamb
      wave-based defect detection procedures. In the proposed approach, a CS algorithm
      based on an alternating minimization (AM) procedure is adopted to extract the
      information about both the system impulse response and the reflectivity function.
      The implemented tool exploits the dispersion compensation properties of the
      warped frequency transform as a means to generate the sparsifying basis for the
      signal representation. The effectiveness of the decomposition task is
      demonstrated on synthetic signals and successfully tested on experimental Lamb
      waves propagating in an aluminum plate. Compared with available strategies, the
      proposed approach provides an improvement in the accuracy of wave propagation
      path length estimation, a fundamental step in defect localization procedures. 

PMID- 24081258
TI  - Piezoelectric rotational mixer based on a first bending vibration mode.
AB  - We propose a miniature piezoelectric mixer that can rotate a liquid inside a hole
      of several millimeters diameter. The mixer has dimensions 14 * 14 * 10 mm with a
      through-hole (7 mm), and piezoelectric elements bonded to its four identical
      sides. When the first bending vibration mode of the mixer is excited by ac
      voltages, rotational flow of liquid is generated by the rotation of an acoustic
      field (acoustic streaming) in the through-hole. This technology is useful in
      automating mixing processes such as the mixing by hand of a few drops of blood in
      medical testing. In this paper, we verify the driving principle experimentally
      and examine the characteristics of a prototype mixer, including the induced flow
      velocity, under changes of the amplitude and frequency of the applied voltages. A
      plastic test tube, used to prevent contamination, is inserted to the through
      hole, and the liquid inside the tube is mixed by rotation of the acoustic field. 

PMID- 24081259
TI  - Moderately reverberant learning ultrasonic pinch panel.
AB  - Tactile sensing is widely used in human-computer interfaces. However, mechanical
      integration of touch technologies is often perceived as difficult by engineers
      because it often limits the freedom of style or form factor requested by
      designers. Recent work in active ultrasonic touch technologies has made it
      possible to transform thin glass plates, metallic sheets, or plastic shells into
      interactive surfaces. The method is based on a learning process of touch-induced,
      amplitude-disturbed diffraction patterns. This paper proposes, first, an
      evolution in the design with multiple dipole transducers that improves touch
      sensitivity or maximum panel size by a factor of ten, and improves robustness and
      usability in moderately reverberant panels, and second, defines a set of acoustic
      variables in the signal processing for the evaluation of sensitivity and
      radiating features. For proof of concept purposes, the design and process are
      applied to 3.2- and 6-mm-thick glass plates with variable damping conditions.
      Transducers are bonded to only one short side of the rectangular substrates.
      Measurements show that the highly sensitive free lateral sides are perfectly
      adapted for pinch-touch and pinch-slide interactions. The advantage of relative
      versus absolute touch disturbance measurement is discussed, together with
      tolerance to abutting contaminants. 

PMID- 24081260
TI  - Enhanced acoustoelectric coupling in acoustic energy harvester using dual
      Helmholtz resonators.
AB  - In this paper, enhanced acoustoelectric transduction in an acoustic energy
      harvester using dual Helmholtz resonators has been reported. The harvester uses a
      pair of cavities mechanically coupled with a compliant perforated plate to
      enhance the acoustic coupling between the cavity and the plate. The experimental
      results show that the volume optimization of the second cavity can significantly
      increase the generated electric voltage up to 400% and raise the output power to
      16 times as large as that of a harvester using a single Helmholtz resonator at
      resonant frequencies primarily related to the plate. 

PMID- 24081261
TI  - Tunable filters using wideband elastic resonators.
AB  - Currently, an ultra-wideband resonator is greatly needed to realize a tunable
      filter with a wide tunable range, because mobile phones with multiple bands and
      cognitive radio systems require such tunable filters to simplify their circuits.
      Although tunable filters have been studied using SAW resonators, their tunable
      range was insufficient for the filters even when wideband SAW resonators with a
      bandwidth of 17% were used. Therefore, the fabrication of wider-bandwidth
      resonators has been attempted with the goal of realizing tunable filters with
      wide tunable ranges. In this study, an SH0- mode plate wave resonator in a 27.5
      degrees YX-LiNbO3 plate with an ultra-wide bandwidth of 29.1%, a high impedance
      ratio of 98 dB, and a high Q (Q(r) = 700 and Q(a) = 720) was realized. Two types
      of tunable filters were constructed using such SH0-mode resonators and
      capacitors. As a result, tunable ranges (bands) of 13% to 19% were obtained. The
      possibility of applying the SH0-mode resonator in the high-frequency gigahertz
      range is discussed.

PMID- 24081262
TI  - A numerical method to derive accurate temperature coefficients of material
      constants from high-temperature SAW measurements: application to langasite.
AB  - The design of wireless SAW sensors for high-temperature applications requires
      accurate knowledge of the constitutive materials' physical properties in the
      desired temperature range. In particular, it is crucial to use reliable
      temperature coefficients of the stiffness, piezoelectric, dielectric, and
      expansion constants of the propagation medium to achieve correct simulations of
      the considered devices. Currently, the best-suited piezoelectric material for
      high-temperature SAW applications is langasite (LGS). Unfortunately, the
      available coefficients do not allow for precise prediction of the temperature
      dependence of LGS-based SAW devices above 300 degrees C. A novel method, based on
      a simulated annealing algorithm coupled with a Rayleigh wave simulation program,
      was developed to find optimal LGS temperature coefficients. This approach has
      proven to yield accurate results up to at least 800 degrees C.

PMID- 24081263
TI  - Piezoelectric fiber-composite-based cantilever sensor for electric-field-induced
      strain measurement in soft electroactive polymer.
AB  - Polymeric materials have been widely used in electronic and electromechanical
      transducer applications. Because of their low elastic modulus, it is quite
      challenging to accurately characterize the electric-field-induced strain and
      elastic modulus by conventional contact methods. In this paper, a piezoelectric
      lead zirconate titanate (PZT) fiber-composite-based cantilever strain sensor has
      been investigated to accurately characterize the electric-field-induced strain
      response in the out-of-plane direction of soft electroactive polymer samples. By
      choosing appropriate substrate material and the thickness ratio of the fiber
      composite to the substrate, this strain sensor can be optimized to provide high
      sensitivity and high flexibility simultaneously. The high voltage sensitivity can
      be attributed to partial decoupling of the longitudinal and transverse
      piezoelectric responses, the improved piezoelectric coefficient and small
      dielectric permittivity. The high flexibility is due to the reduced flexural
      spring constant of the composite-based cantilever device. Both theoretical
      modeling of the PZT fiber-composite-based cantilever device and experimental
      verification are performed in this work. The results indicate that the
      piezoelectric PZT fiber-composite-based cantilever strain sensor can accurately
      characterize the electric-field-induced small strain in electroactive soft
      polymers with high reliability.

PMID- 24081264
TI  - Analysis of a piezoelectric power harvester with adjustable frequency by precise
      electric field method.
AB  - A power harvester with adjustable frequency, which consists of a hinged-hinged
      piezoelectric bimorph and a concentrated mass, is studied by the precise electric
      field method (PEFM), taking into account a distribution of the electric field
      over the thickness. Usually, using the equivalent electric field method (EEFM),
      the electric field is approximated as a constant value in the piezoelectric
      layer. Charge on the upper electrode (UEC) of the bimorph is often assumed as
      output charge. However, different output charge can be obtained by integrating on
      electric displacement over the electrode with different thickness coordinates.
      Therefore, an average charge (AC) on thickness is often assumed as the output
      value. This method is denoted EEFM AC. The flexural vibration of the bimorph is
      calculated by the three methods and their results are compared. Numerical results
      illustrate that EEFM UEC overestimates resonant frequency, output power, and
      efficiency. EEFM AC can accurately calculate the output power and efficiency, but
      underestimates resonant frequency. The performance of the harvester, which
      depends on concentrated mass weight, position, and circuit load, is analyzed
      using PEFM. The resonant frequency can be modulated 924 Hz by moving the
      concentrated mass along the bimorph. This feature suggests that the natural
      frequency of the harvester can be adjusted conveniently to adapt to frequency
      fluctuation of the ambient vibration.

PMID- 24081265
TI  - Interdigitated-electrode-based MEMS-scale piezoelectric energy harvester modeling
      and optimization using finite element method.
AB  - This paper presents a novel optimization method for interdigitated electrode
      (IDE)-based, cantilever-type piezoelectric energy harvesters at
      microelectromechanical system (MEMS) scale. A new two-stage approach based on the
      finite element method is proposed to examine the performance of such devices.
      First, detailed electrostatic poling simulations are presented. The results of
      these poling orientation simulations are used while calculating electrical energy
      and conversion efficiency in response to a constant external force. The proposed
      approach is used to find the optimum piezoelectric material thickness and IDE
      geometry for a cantilever beam which is constructed on top of a 4-MUm Si
      structural layer and a 1-MUm SiO2 isolation layer. Cantilever and IDE lengths are
      fixed at 320 MUm and 240 MUm, respectively, whereas the lead zirconate titanate
      (PZT) thickness, IDE finger widths, and number of finger pairs are varied.
      Maximum output energy of 0.37 pJ for a 15-MUN force is obtained at a PZT
      thickness of 0.6 MUm and an IDE consisting of 12 finger pairs. This energy is
      reduced to 1.5 fJ for 5 MUm PZT thickness with 2 electrode finger pairs, which
      shows that device geometry has a significant impact on device performance. The
      proposed method presents an accurate framework for the rapid design and
      performance prediction of novel piezoelectric energy harvester structures. 

PMID- 24081266
TI  - Thickness design, fabrication, and evaluation of 100-MHz polyurea ultrasonic
      transducer.
AB  - In this paper, we present a polyurea transducer that works at 100 MHz under
      water. The transducer was designed using an equivalent circuit model so that an
      aluminum (top)-polyurea-aluminum (bottom)-polyimide layer had a resonant
      frequency of 100 MHz and output sound pressure became maximum at that frequency.
      The thicknesses of the top aluminum electrode, polyurea, and bottom aluminum
      electrode were determined to be 3.3, 3.5, and 1.7 MUm, respectively. A 100-MHz
      polyurea transducer with the designed thickness was fabricated using deposition
      equipment. To evaluate the performance of the designed and fabricated polyurea
      transducer, transmission-reception experiments with pulsed and burst waves were
      carried out. The results show that transmitting and receiving ultrasounds at a
      frequency of 100 MHz are possible as expected with the thickness design. To
      evaluate actual use, B-mode imaging of an onion was also performed using the
      transducer, which was formed into a line-focused shape. The result shows that the
      outer layer of the onion, of 0.1 to 0.2 mm thickness, was successfully imaged. 

PMID- 24081267
TI  - Propagation of SH waves in functionally gradient electromagnetoelastic half
      space.
AB  - The propagation of shear-horizontal (SH) waves is studied for a functionally
      gradient magnetoelectric (ME) material. The material properties of the ME half
      space are normal to the free surface. The ME open conditions are applied to the
      free surface. Dispersion relations are obtained in explicit form for different
      forms of the nonhomogeneities. 

PMID- 24081268
TI  - Dynamic characteristics of an axially polarized multilayer piezoelectric/elastic
      composite cylindrical transducer.
AB  - An analytical model of the dynamic characteristics of an axially polarized
      multilayer piezoelectric/elastic composite cylindrical transducer is proposed in
      this paper. Based on the plane stress assumption, the dynamic analytical solution
      of the transducer under an external harmonic voltage load is obtained, and the
      electric admittance is also derived analytically. Inherent properties of the
      transducer, such as resonance and anti-resonance frequencies, are presented and
      discussed. In addition, comparisons with other related investigations are also
      given, and good agreement is found. The present investigation is very helpful for
      the design of axially polarized multilayer piezoelectric/elastic composite
      cylindrical transducers, which can be used in applications related to ultrasonic
      and underwater sound waves. 

PMID- 24081269
TI  - Sensing properties of the Anisimkin Jr. acoustic modes in uncoated ST-quartz
      plates.
AB  - The Anisimkin Jr. (AN) acoustic plate modes having quasi-longitudinal (QL), quasi
      shear-vertical (QSV) and quasi-shear-horizontal (QSH) polarizations are studied
      experimentally in uncoated ST,X-quartz plates with normalized plate thicknesses
      h/lambda = 1.485 and 1.67 (where h is thickness and lambda is wavelength). The
      sensitivities of the modes toward mass loading (water vapor) are measured at
      different temperatures in the range 10.6 degrees C to 23 degrees C and compared
      with that of the Rayleigh SAW. The sensitivity of the same modes toward
      temperature is measured from 15 degrees C to 85 degrees C and compared with those
      of the bulk waves propagating in the same direction. Acoustic plate modes with
      dominant responses toward humidity or temperature are found. 

PMID- 24081270
TI  - Modeling nonlinear wave propagation on nonuniform grids using a mapped k-space
      pseudospectral method.
AB  - Simulating the propagation of nonlinear ultrasound waves is computationally
      difficult because of the dense grids needed to capture high-frequency harmonics.
      Here, a mapped k-space pseudospectral method is presented which allows the use of
      nonuniform grid spacings. This enables grid points to be clustered around steep
      regions of the wave field. Compared with using a uniform grid, this significantly
      reduces the total number of grid points needed for accurate simulations. Two
      methods for selecting a suitable nonuniform grid mapping are discussed. 

PMID- 24081271
TI  - A piezoelectric energy harvester with increased bandwidth based on beam flexural
      vibrations in perpendicular directions.
AB  - We propose a new structure for piezoelectric energy harvesters. It consists of an
      elastic beam with two pairs of piezoelectric films operating with the fundamental
      flexural modes in perpendicular directions. A one-dimensional model is developed
      and used to analyze the proposed structure. The output power density is
      calculated and examined. Results show that, with simultaneous flexural motions in
      two perpendicular directions, the output power has two peaks close to each other
      resulting from the two fundamental flexural resonances. The distance between the
      two peaks can be adjusted through design to make the two peaks merge into one
      wide peak. Hence, the frequency bandwidth through which energy can be harvested
      is roughly doubled when compared with conventional beam bimorph energy harvesters
      operating with flexural motion in one direction and one resonance only. 

PMID- 24081272
TI  - Theoretical and experimental study of the electroacoustic behavior of lithium
      niobate under an initial mechanical stress.
AB  - Recently, a second-order formalism of piezoelectric structures under an external
      mechanical stress was developed. Because the yield strength of lithium niobate
      was unknown, this study was not able to describe and evaluate realistic benefits
      of a prestress load on electromechanical properties. Therefore, in this study,
      experimental determination of the yield strength of lithium niobate sample is
      performed and shows that this limit is close to 110 MPa. Then, the nonlinearities
      and evolutions of electroacoustic parameters of this piezoelectric material under
      mechanical stress are numerically studied. By varying the initial prestress, as
      well as azimuthal and elevation angles, the cut planes in which a prestress
      induces significant benefits on velocities and coupling coefficient are
      identified. Finally, approximate relations describing changes between
      electroacoustic parameters defined in the two coordinate systems of the study are
      determined. 

PMID- 24081273
TI  - An efficient pulse compression method of chirp-coded excitation in medical
      ultrasound imaging.
AB  - Coded excitation can improve the SNR in medical ultrasound imaging. In coded
      excitation, pulse compression is applied to compress the elongated coded signals
      into a short pulse, which typically requires high computational complexity, i.e.,
      a compression filter with a few hundred coefficients. In this paper, we propose
      an efficient pulse compression method of chirp-coded excitation, in which the
      pulse compression is conducted with complex baseband data after downsampling, to
      lower the computational complexity. In the proposed method, although compression
      is conducted with the complex data, the L-fold downsampling is applied for
      reducing both data rates and the number of compression filter coefficients; thus,
      total computational complexity is reduced to the order of 1/L(2). The proposed
      method was evaluated with simulation and phantom experiments. From the simulation
      and experiment results, the proposed pulse compression method produced similar
      axial resolution compared with the conventional pulse compression method with
      negligible errors, i.e., ?36 dB in signal-to-error ratio (SER). These results
      indicate that the proposed method can maintain the performance of pulse
      compression of chirp-coded excitation while substantially reducing computational
      complexity.

PMID- 24081274
TI  - [Current controversies in neuroethics].

PMID- 24081275
TI  - [Biologism controversy: ethical implications for psychiatry].
AB  - Current biological psychiatry, it is frequently claimed by its opponents, is
      "biologistic" and unduly narrows psychological disorders to neurobiology and
      molecular biology. They deem a complete neuroscientific reduction of the mental
      phenomena to be impossible because of the impossibility of reducing certain
      phenomena, such as the individual subjective experience. If such a reduction is
      nevertheless undertaken it is ultimately to the disadvantage of the patients. We
      argue in this article that the very term "biologism" has to be put under scrutiny
      in the first place. As a result it becomes obvious that "biologism", as a
      subclass of "philosophical naturalism", is ultimately quite unproblematic.
      Biologism is dangerous only if it implies an eliminative rejection or an
      inappropriate underestimation of the relevance of the psyche. On closer
      examination it gets evident that such implications do not follow necessarily from
      biologism but cannot be precluded either. To better identify and possibly prevent
      such dangers, a more differentiated terminology seems helpful.

PMID- 24081276
TI  - [Motor-independent communication by severely physically challenged patients:
      neuroscientific research results and patient autonomy].
AB  - Motor-independent communication is a novel diagnostic and therapeutic method that
      is currently in development in order to enable communication with severely
      physically challenged patients. Some patients with locked-in syndromes or with
      chronic disorders of consciousness are capable of modulating their brain
      activities to such a degree that the latter can be analyzed regarding
      communicative intentions with neuroscientific technologies, such as functional
      magnetic resonance imaging. Further scientific development and an increasing
      clinical use of motor-independent communication will aid in meeting essential
      quality standards for this method. In particular, the requirements need to be
      clarified under which the method may be utilized to support the patients'
      autonomy by enabling them to make their own decisions about therapeutic
      interventions. Communication mediated by technology promises to significantly
      improve the quality of life for severely physically challenged patients. 

PMID- 24081279
TI  - Floral and mating system divergence in secondary sympatry: testing an alternative
      hypothesis to reinforcement in Clarkia.
AB  - BACKGROUND AND AIMS: Reproductive character displacement (RCD) is often an
      important signature of reinforcement when partially cross-compatible taxa meet in
      secondary sympatry. In this study, floral evolution is examined during the
      Holocene range expansion of Clarkia xantiana subsp. parviflora from eastern
      Pleistocene refugia to a western zone of sympatry with its sister taxon, subsp.
      xantiana. Floral divergence between the two taxa is greater in sympatry than
      allopatry. The goal was to test an alternative hypothesis to reinforcement - that
      floral divergence of sympatric genotypes is simply a by-product of adaptation to
      pollination environments that differ between the allopatric and sympatric
      portions of the subspecies' range. METHODS: Floral trait data from two common
      garden studies were used to examine floral divergence between sympatric and
      allopatric regions and among phylogeographically defined lineages. In natural
      populations of C. x. parviflora, the magnitude of pollen limitation and
      reproductive assurance were quantified across its west-to-east range. Potted
      sympatric and allopatric genotypes were also reciprocally translocated between
      geographical regions to distinguish between the effects of floral phenotype
      versus contrasting pollinator environments on reproductive ecology. KEY RESULTS:
      Sympatric populations are considerably smaller flowered with reduced herkogamy.
      Pollen limitation and the reproductive assurance value of selfing are greater in
      sympatric than in allopatric populations. Most significantly, reciprocal
      translocation experiments showed these differences in reproductive ecology cannot
      be attributed to contrasting pollinator environments between the sympatric and
      allopatric regions, but instead reflect the effects of flower size on pollinator
      attraction. CONCLUSIONS: Floral evolution occurred during the westward range
      expansion of parviflora, particularly in the zone of sympatry with xantiana. No
      evidence was found that strongly reduced flower size in sympatric parviflora (and
      RCD between parviflora and xantiana) is due to adaptation to limited pollinator
      availability. Rather, floral divergence appears to have been driven by other
      factors, such as interactions with congenerics in secondary sympatry.

PMID- 24081277
TI  - [Clinically isolated syndrome].
AB  - A clinically isolated syndrome (CIS) is a term which describes the first clinical
      onset of a potential multiple sclerosis (MS). It ought to be defined as an MS
      stage rather than a separate disease entity; however, with respect to the
      diagnostic work-up, differential diagnoses to be considered, prognostic factors
      for the development of a clinically confirmed MS and initiation of an
      immunomodulatory therapy, there are some important considerations supported by
      recent studies. These considerations as well as the current guidelines are
      critically discussed in this review article. Additionally, recommendations are
      given regarding the management of radiologically isolated syndrome (RIS) an
      imaging-based diagnosis of a potential preclinical stage of MS. 

PMID- 24081280
TI  - Water stress-induced xylem hydraulic failure is a causal factor of tree mortality
      in beech and poplar.
AB  - BACKGROUND AND AIMS: Extreme water stress episodes induce tree mortality, but the
      physiological mechanisms causing tree death are still poorly understood. This
      study tests the hypothesis that a potted tree's ability to survive extreme
      monotonic water stress is determined by the cavitation resistance of its xylem
      tissue. METHODS: Two species were selected with contrasting cavitation resistance
      (beech and poplar), and potted juvenile trees were exposed to a range of water
      stresses, causing up to 100 % plant death. KEY RESULTS: The lethal dose of water
      stress, defined as the xylem pressure inducing 50 % mortality, differed sharply
      across species (1.75 and 4.5 MPa in poplar and beech, respectively). However, the
      relationships between tree mortality and the degree of cavitation in the stems
      were similar, with mortality occurring suddenly when >90 % cavitation had
      occurred. CONCLUSIONS: Overall, the results suggest that cavitation resistance is
      a causal factor of tree mortality under extreme drought conditions.

PMID- 24081281
TI  - Trichome structure and evolution in Neotropical lianas.
AB  - BACKGROUND AND AIMS: Trichomes are epidermal outgrowths generally associated with
      protection against herbivores and/or desiccation that are widely distributed from
      ferns to angiosperms. Patterns of topological variation and morphological
      evolution of trichomes are still scarce in the literature, preventing valid
      comparisons across taxa. This study integrates detailed morphoanatomical data and
      the evolutionary history of the tribe Bignonieae (Bignoniaceae) in order to gain
      a better understanding of current diversity and evolution of trichome types.
      METHODS: Two sampling schemes were used to characterize trichome types: (1)
      macromorphological characterization of all 105 species currently included in
      Bignonieae; and (2) micromorphological characterization of 16 selected species.
      Individual trichome morphotypes were coded as binary in each vegetative plant
      part, and trichome density and size were coded as multistate. Ancestral character
      state reconstructions were conducted using maximum likelihood (ML) assumptions.
      KEY RESULTS: Two main functional trichome categories were found: non-glandular
      and glandular. In glandular trichomes, three morphotypes were recognized: peltate
      (Pg), stipitate (Sg) and patelliform/cupular (P/Cg) trichomes. Non-glandular
      trichomes were uniseriate, uni- or multicellular and simple or branched. Pg and
      P/Cg trichomes were multicellular and non-vascularized with three clearly
      distinct cell layers. Sg trichomes were multicellular, uniseriate and long
      stalked. ML ancestral character state reconstructions suggested that the most
      recent common ancestor (MRCA) of Bignonieae probably had non-glandular, Pg and
      P/Cg trichomes, with each trichome type presenting alternative histories of
      appearance on the different plant parts. For example, the MRCA of Bignonieae
      probably had non-glandular trichomes on the stems, prophylls, petiole, petiolule
      and leaflet veins while P/Cg trichomes were restricted to leaflet blades. Sg
      trichomes were not present in the MRCA of Bignonieae independently of the
      position of these trichomes. These trichomes had at least eight independent
      origins in tribe. CONCLUSIONS: The patterns of trichome evolution indicate that
      most morphotypes are probably homologous in Bignonieae and could be treated under
      the same name based on its morphological similarity and common evolutionary
      history, in spite of the plethora of names that have been previously designated
      in the literature. The trichome descriptions presented here will facilitate
      comparisons across taxa, allowing inferences on the relationsthips between
      trichome variants and future studies about their functional properties.

PMID- 24081282
TI  - Winter-summer succession of unicellular eukaryotes in a meso-eutrophic coastal
      system.
AB  - The objective of this study was to explore the succession of planktonic
      unicellular eukaryotes by means of 18S rRNA gene tag pyrosequencing in the
      eastern English Channel (EEC) during the winter to summer transition. The 59 most
      representative (>0.1%, representing altogether 95% of total reads), unique
      operational taxonomic units (OTUs) from all samples belonged to 18 known high
      level taxonomic groups and 1 unaffiliated clade. The five most abundant OTUs
      (69.2% of total reads) belonged to Dinophyceae, Cercozoa, Haptophyceae, marine
      alveolate group I, and Fungi. Cluster and network analysis between samples
      distinguished the winter, the pre-bloom, the Phaeocystis globosa bloom and the
      post-bloom early summer conditions. The OTUs-based network revealed that P.
      globosa showed a relatively low number of connections-most of them negative-with
      all other OTUs. Fungi were linked to all major taxonomic groups, except
      Dinophyceae. Cercozoa mostly co-occurred with the Fungi, the Bacillariophyceae
      and several of the miscellaneous OTUs. This study provided a more detailed
      exploration into the planktonic succession pattern of the EEC due to its
      increased depth of taxonomic sampling over previous efforts based on classical
      monitoring observations. Data analysis implied that the food web concept in a
      coastal system based on predator-prey (e.g. grazer-phytoplankton) relationships
      is just a part of the ecological picture; and those organisms exploiting a
      variety of strategies, such as saprotrophy and parasitism, are persistent and
      abundant members of the community.

PMID- 24081283
TI  - Optimal age classification of young individuals based on dental evidence in civil
      and criminal proceedings.
AB  - BACKGROUND: Criminal cases involving young people, irregular immigration and the
      many issues related to asylum seekers has increased the judicial demand of age
      estimation. Calcification of teeth and specifically of third molar has
      demonstrated to be reliable evidence to estimate age respect to 18 years
      threshold of age. AIMS: As prosecution of research of Pinchi et al. (2010) and
      Corradi et al. (J Forensic Sci 58:51-59, 2013), the study aims to evaluate if
      tuning the size of the zone of indifference posed around the age threshold
      improves the performances of the age classification model. MATERIALS AND METHODS:
      The sample was composed of 1,560 OPGs of Italian subjects aged between 15 and 22
      years. Third molar calcification stage was assessed according to Demirjian's
      scale by three different experts. Intra- and inter-operator variability has been
      calculated. The statistical analysis was provided by a Modified Naive Bayesian
      allowing the use of soft evidence. Rate of in/correct classification was provided
      for individuals classified at a very high level of probability (90 %), as needed
      for criminal cases, and for a lower probability level (51 %) as it suffices for
      civil cases. RESULTS: The intra-observer reproducibility varies between 79.2 and
      89.2 % with soft evidence, whilst it decreases from values between 0.589 and
      0.763, when only hard evidence is allowed to experts showing the usefulness of
      the MBN approach. In civil cases, imposing the constraint of classifying at least
      95 % of the individuals, the method achieved a rate of correct classification in
      the range 80-83 % depending on the expert. In criminal cases, we tuned the ZOI
      size to achieve 85 % of individuals correctly classified and the model succeeded
      in classifying 66-81 % of the sample, the variability still being dependent on
      the expert's ability. CONCLUSIONS: After a review of several studies concerning
      the age classification of young individuals by using dental evidence, we must
      conclude that it is almost impossible to make a comparison among them. To rank
      the effectiveness of different methods is to challenge them with the same problem
      and data, looking at the results measured by the same accepted scoring rule. It
      could also be interesting to repeat the experiment in different conditions
      varying the reference population and considering if some important covariates,
      like sex and health status, influence the model performances.

PMID- 24081284
TI  - Primary care utilization and colorectal cancer incidence and mortality among
      Medicare beneficiaries: a population-based, case-control study.
AB  - BACKGROUND: Utilization of primary care may decrease colorectal cancer (CRC)
      incidence and death through greater receipt of CRC screening tests. OBJECTIVE: To
      examine the association of primary care utilization with CRC incidence, CRC
      deaths, and all-cause mortality. DESIGN: Population-based, case-control study.
      SETTING: Medicare program. PARTICIPANTS: Persons aged 67 to 85 years diagnosed
      with CRC between 1994 and 2005 in U.S. Surveillance, Epidemiology, and End
      Results (SEER) regions matched with control patients (n = 205,804 for CRC
      incidence, 54,160 for CRC mortality, and 121,070 for all-cause mortality).
      MEASUREMENTS: Primary care visits in the 4- to 27-month period before CRC
      diagnosis, CRC incidence, CRC mortality, and all-cause mortality. RESULTS:
      Compared with persons having 0 or 1 primary care visit, persons with 5 to 10
      visits had lower CRC incidence (adjusted odds ratio [OR], 0.94 [95% CI, 0.91 to
      0.96]) and mortality (adjusted OR, 0.78 [CI, 0.75 to 0.82]) and lower all-cause
      mortality (adjusted OR, 0.79 [CI, 0.76 to 0.82]). Associations were stronger in
      patients with late-stage CRC diagnosis, distal lesions, and diagnosis in more
      recent years when there was greater Medicare screening coverage. Ever receipt of
      CRC screening and polypectomy mediated the association of primary care
      utilization with CRC incidence. LIMITATION: This study used administrative data,
      which made it difficult to identify potential confounders and prevented
      examination of the content of primary care visits. CONCLUSION: Medicare
      beneficiaries with higher utilization of primary care have lower CRC incidence
      and mortality and lower overall mortality. Increasing and promoting access to
      primary care in the United States for Medicare beneficiaries may help decrease
      the national burden of CRC. PRIMARY FUNDING SOURCE: American Cancer Society.

PMID- 24081285
TI  - Outcomes among patients discharged from busy intensive care units.
AB  - BACKGROUND: Strains on the capacities of intensive care units (ICUs) may
      influence the quality of ICU-to-floor transitions. OBJECTIVE: To determine how 3
      metrics of ICU capacity strain (ICU census, new admissions, and average acuity)
      measured on days of patient discharges influence ICU length of stay (LOS) and
      post-ICU discharge outcomes. DESIGN: Retrospective cohort study from 2001 to
      2008. SETTING: 155 ICUs in the United States. PATIENTS: 200 730 adults discharged
      from ICUs to hospital floors. MEASUREMENTS: Associations between ICU capacity
      strain metrics and discharged patient ICU LOS, 72-hour ICU readmissions,
      subsequent in-hospital death, post-ICU discharge LOS, and hospital discharge
      destination. RESULTS: Increases in the 3 strain variables on the days of ICU
      discharge were associated with shorter preceding ICU LOS (all P < 0.001) and
      increased odds of ICU readmissions (all P < 0.050). Going from the 5th to 95th
      percentiles of strain was associated with a 6.3-hour reduction in ICU LOS (95%
      CI, 5.3 to 7.3 hours) and a 1.0% increase in the odds of ICU readmission (CI,
      0.6% to 1.5%). No strain variable was associated with increased odds of
      subsequent death, reduced odds of being discharged home from the hospital, or
      longer total hospital LOS. LIMITATION: Long-term outcomes could not be measured.
      CONCLUSION: When ICUs are strained, triage decisions seem to be affected such
      that patients are discharged from the ICU more quickly and, perhaps
      consequentially, have slightly greater odds of being readmitted to the ICU.
      However, short-term patient outcomes are unaffected. These results suggest that
      bed availability pressures may encourage physicians to discharge patients from
      the ICU more efficiently and that ICU readmissions are unlikely to be causally
      related to patient outcomes. PRIMARY FUNDING SOURCE: Agency for Healthcare
      Research and Quality; National Heart, Lung, and Blood Institute; and Society of
      Critical Care Medicine.

PMID- 24081286
TI  - Underreporting high-risk prescribing among Medicare Advantage plans: a cross
      sectional analysis.
AB  - BACKGROUND: Although Medicare Advantage plans are required to report clinical
      performance using Healthcare Effectiveness Data and Information Set (HEDIS)
      quality indicators, the accuracy of plan-reported performance rates is unknown.
      OBJECTIVE: To compare calculated and reported rates of high-risk prescribing
      among Medicare Advantage plans. DESIGN: Cross-sectional comparison. SETTING: 172
      Medicare Advantage plans. PATIENTS: A random sample of beneficiaries in 172
      Medicare Advantage plans in 2006 (n = 177,227) and 2007 (n = 173,655).
      MEASUREMENTS: Plan-reported HEDIS rates of high-risk prescribing among elderly
      persons were compared with rates calculated from Medicare Advantage plans' Part D
      claims by using the same measure specifications and source population. RESULTS:
      The mean rate of high-risk prescribing derived from Part D claims was 26.9% (95%
      CI, 25.9% to 28.0%), whereas the mean plan-reported rate was 21.1% (CI, 20.0% to
      22.3%). Approximately 95% of plans underreported rates of high-risk prescribing
      relative to calculated rates derived from Part D claims. The differences in the
      calculated and reported rates negatively affected quality rankings for the plans
      that most accurately reported rates. For example, the 9 plans that reported rates
      of high-risk prescribing within 1 percentage point of calculated rates were
      ranked 43.4 positions lower when reported rates were used instead of calculated
      rates. Among 103,680 individuals present in both the sample of Part D claims and
      HEDIS data in 2006, Medicare Advantage plans incorrectly excluded 10.3% as
      ineligible for the HEDIS high-risk prescribing measure. Among those correctly
      included in the high-risk prescribing denominator, the reported rate of high-risk
      prescribing was 21.9% and the calculated rate was 26.2%. LIMITATION: A single
      quality measure was assessed. CONCLUSION: Medicare Advantage plans underreport
      rates of high-risk prescribing, suggesting a role for routine audits to ensure
      the validity of publicly reported quality measures. PRIMARY FUNDING SOURCE:
      Health Assessment Lab and National Institute on Aging.

PMID- 24081288
TI  - Should hospitals look like airports?

PMID- 24081287
TI  - Risk-benefit profile of long-term dual- versus single-antiplatelet therapy among
      patients with ischemic stroke: a systematic review and meta-analysis.
AB  - BACKGROUND: Dual-antiplatelet regimens for prevention of recurrent stroke promote
      antithrombotic effects but may increase the risk for hemorrhage. PURPOSE: To
      qualitatively and quantitatively examine the risk for recurrent stroke and
      intracranial hemorrhage (ICH) linked to long-term dual- and single-antiplatelet
      therapy among patients with ischemic stroke and transient ischemic attack. DATA
      SOURCES: PubMed, EMBASE, and the Cochrane Central Register of Controlled Trials
      through March 2013 without language restrictions. STUDY SELECTION: The search
      identified 7 randomized, controlled trials that involved a total of 39,574
      participants and reported recurrent stroke and ICH as outcome measures. DATA
      EXTRACTION: All data from eligible studies were independently abstracted by 2
      investigators according to a standard protocol. DATA SYNTHESIS: Recurrent stroke
      risk did not differ between patients receiving dual-antiplatelet therapy and
      those receiving aspirin monotherapy (relative risk [RR], 0.89 [95% CI, 0.78 to
      1.01]) or clopidogrel monotherapy (RR, 1.01 [CI, 0.93 to 1.08]). Risk for ICH did
      not differ between patients receiving dual-antiplatelet therapy and those
      receiving aspirin monotherapy (RR, 0.99 [CI, 0.70 to 1.42]) but was greater among
      patients receiving dual-antiplatelet therapy than among those receiving
      clopidogrel monotherapy (RR, 1.46 [CI, 1.17 to 1.82]). LIMITATION: Agents used in
      dual- and single-antiplatelet therapies varied across trials, and the relatively
      modest number of trials limited subgroup analysis. CONCLUSION: Compared with
      monotherapy, dual-antiplatelet therapy lasting more than 1 year after an index
      ischemic stroke or transient ischemic attack is not associated with a greater
      reduction in overall recurrent stroke risk. However, long-term dual-antiplatelet
      therapy is linked to higher risk for ICH than clopidogrel monotherapy in this
      patient population. PRIMARY FUNDING SOURCE: Chang Gung Memorial Hospital.

PMID- 24081289
TI  - Making the case for the benefits of primary care from observational studies: does
      an ounce of prevention take a pound of doctor visits?

PMID- 24081290
TI  - Underreporting potentially inappropriate prescribing for older outpatients: does
      it matter?

PMID- 24081291
TI  - Alligator hands.

PMID- 24081293
TI  - The outside hospital.

PMID- 24081295
TI  - Aspirin versus low-molecular-weight heparin after total hip arthroplasty.

PMID- 24081296
TI  - Aspirin versus low-molecular-weight heparin after total hip arthroplasty.

PMID- 24081297
TI  - Hepatotoxicity associated with the dietary supplement N.O.-XPLODE.

PMID- 24081298
TI  - Summaries for patients. Using primary care services can help reduce the burden of
      colorectal cancer.

PMID- 24081299
TI  - Systemic lupus erythematosus.

PMID- 24081300
TI  - Urinary nickel and prolactin in workers exposed to urban stressors.
AB  - The aim of our study is to verify whether the exposure to low Ni doses in urban
      air may have some effects on the prolactin values of outdoor workers exposed to
      urban pollutants. 334 workers have been included in the study and divided on the
      basis of gender, job, age, length of service and smoking habits. Each worker
      underwent urinary Ni and prolactin sampling. The t-test for independent samples,
      the Mann-Whitney U test for two mode variables (gender, smoking habit), the
      univariate ANOVA test and the Kruskal Wallis test for the variables in more than
      two modes (age, length of service and job duties) were performed on the total
      sample. Pearson's correlation coefficient (p two-tailed) among the parameters was
      evaluated both in the total sample and after the stratification by gender,
      smoking habit and job. Multiple linear regression was performed after taking
      account of the major confounding factors on the total sample and on the
      subcategories. The statistical tests showed a significant correlation between
      urinary Ni and prolactin both in the total sample and in the subcategories. We
      believe that the occupational exposure to low doses of Ni present in urban
      pollution may influence the prolactin values in exposed workers. 

PMID- 24081301
TI  - Goal setting with type 2 diabetes: a hermeneutic analysis of the experiences of
      diabetes educators.
AB  - PURPOSE: The purpose of this study was to explicate and interpret common
      experiences of diabetes educators (DEs) with patient goal setting for patients
      with type 2 diabetes in diabetes education. METHODS: Transcripts (n = 10) from
      semi-structured interviews were analyzed using a hermeneutic phenomenological
      approach to more deeply explore the accounts of DEs' goal setting with patients
      with type 2 diabetes. RESULTS: The overarching pattern that emerged was "Striking
      a Balance," which subsumed 4 subthemes: Applying Theoretical-Practical Principles
      When Setting Goals, Identifying Idealistic-Realistic Expectations, Creating
      Patient-Educator-Centered Plans, and Readying-Living With Goal Setting. The
      pattern, "Striking a Balance," revealed a common meaning of DEs as experiences
      requiring balance and nuance in goal setting with patients. IMPLICATIONS: The
      results of this study combined with the tenets of the self-determination theory
      can provide the DEs with real-life exemplars and a theoretical framework to
      encourage their patients to self-manage, increase intrinsic motivation, and
      improve adherence related to their lifestyle changes and glycemic control. DEs,
      as facilitators of change, can implement these changes with flexible and
      reciprocal activities with their patients. The DEs owned these activities and
      they are: "building the bond," "sharing the session," "readying for change,"
      "sending them home," and "bringing them back."

PMID- 24081302
TI  - Imprinted and X-linked non-coding RNAs as potential regulators of human placental
      function.
AB  - Pregnancy outcome is inextricably linked to placental development, which is
      strictly controlled temporally and spatially through mechanisms that are only
      partially understood. However, increasing evidence suggests non-coding RNAs
      (ncRNAs) direct and regulate a considerable number of biological processes and
      therefore may constitute a previously hidden layer of regulatory information in
      the placenta. Many ncRNAs, including both microRNAs and long non-coding
      transcripts, show almost exclusive or predominant expression in the placenta
      compared with other somatic tissues and display altered expression patterns in
      placentas from complicated pregnancies. In this review, we explore the results of
      recent genome-scale and single gene expression studies using human placental
      tissue, but include studies in the mouse where human data are lacking. Our review
      focuses on the ncRNAs epigenetically regulated through genomic imprinting or X
      chromosome inactivation and includes recent evidence surrounding the H19 lincRNA,
      the imprinted C19MC cluster microRNAs, and X-linked miRNAs associated with
      pregnancy complications. 

PMID- 24081304
TI  - STAT1 negatively regulates spatial memory formation and mediates the memory
      impairing effect of Abeta.
AB  - Signal transducer and activator of transcription-1 (STAT1) has an important role
      in inflammation and the innate immune response, but its role in the central
      nervous system is less well understood. Here, we examined the role of STAT1 in
      spatial learning and memory, and assessed the involvement of STAT1 in mediating
      the memory-impairing effect of amyloid-beta (Abeta). We found that water maze
      training downregulated STAT1 expression in the rat hippocampal CA1 area, and
      spatial learning and memory function was enhanced in Stat1-knockout mice.
      Conversely, overexpression of STAT1 impaired water maze performance. STAT1
      strongly upregulated the expression of the extracellular matrix protein laminin
      beta1 (LB1), which also impaired water maze performance in rats. Furthermore,
      Abeta impaired spatial learning and memory in association with a dose-dependent
      increase in STAT1 and LB1 expression, but knockdown of STAT1 and LB1 both
      reversed this effect of Abeta. This Abeta-induced increase in STAT1 and LB1
      expression was also associated with a decrease in the expression of the N-methyl
      D-aspartate receptor (NMDAR) subunits, NR1, and NR2B. Overexpression of NR1 or
      NR2B or exogenous application of NMDA reversed Abeta-induced learning and memory
      deficits as well as Abeta-induced STAT1 and LB1 expression. Our results
      demonstrate that STAT1 negatively regulates spatial learning and memory through
      transcriptional regulation of LB1 expression. We also identified a novel
      mechanism for Abeta pathogenesis through STAT1 induction. Notably, impairment of
      spatial learning and memory by this STAT1-mediated mechanism is independent of
      cAMP responsive element-binding protein signaling. 

PMID- 24081303
TI  - Acamprosate produces its anti-relapse effects via calcium.
AB  - Alcoholism is one of the most prevalent neuropsychiatric diseases, having an
      enormous health and socioeconomic impact. Along with a few other medications,
      acamprosate (Campral-calcium-bis (N-acetylhomotaurinate)) is clinically used in
      many countries for relapse prevention. Although there is accumulated evidence
      suggesting that acamprosate interferes with the glutamate system, the molecular
      mode of action still remains undefined. Here we show that acamprosate does not
      interact with proposed glutamate receptor mechanisms. In particular, acamprosate
      does not interact with NMDA receptors or metabotropic glutamate receptor group I.
      In three different preclinical animal models of either excessive alcohol
      drinking, alcohol-seeking, or relapse-like drinking behavior, we demonstrate that
      N-acetylhomotaurinate by itself is not an active psychotropic molecule. Hence,
      the sodium salt of N-acetylhomotaurinate (i) is ineffective in alcohol-preferring
      rats to reduce operant responding for ethanol, (ii) is ineffective in alcohol
      seeking rats in a cue-induced reinstatement paradigm, (iii) and is ineffective in
      rats with an alcohol deprivation effect. Surprisingly, calcium salts produce
      acamprosate-like effects in all three animal models. We conclude that calcium is
      the active moiety of acamprosate. Indeed, when translating these findings to the
      human situation, we found that patients with high plasma calcium levels due to
      acamprosate treatment showed better primary efficacy parameters such as time to
      relapse and cumulative abstinence. We conclude that N-acetylhomotaurinate is a
      biologically inactive molecule and that the effects of acamprosate described in
      more than 450 published original investigations and clinical trials and 1.5
      million treated patients can possibly be attributed to calcium. 

PMID- 24081305
TI  - Headache and focal neurologic deficits in a 37-year-old woman.
AB  - A 37-year-old woman presented with progressively worsening headache. She had no
      headache history, and initial evaluation revealed hydrocephalus of unclear
      etiology. A ventriculoperitoneal shunt was placed with improvement. However, her
      headache returned and she developed neurologic deficits. Imaging studies
      demonstrated multiple cystic lesions in the posterior fossa. Serum and
      cerebrospinal fluid studies were unrevealing and a biopsy of the cystic lesions
      was performed. The clinical approach, differential diagnosis, and
      neuropathological findings are discussed. 

PMID- 24081306
TI  - A corona discharge atmospheric pressure chemical ionization source with selective
      NO(+) formation and its application for monoaromatic VOC detection.
AB  - We have developed a new type of corona discharge (CD) for atmospheric pressure
      chemical ionization (APCI) for application in ion mobility spectrometry (IMS) as
      well as in mass spectrometry (MS). While the other CD-APCI sources are able to
      generate H3O(+).(H2O)n as the major reactant ions in N2 or in zero air, the
      present CD-APCI source has the ability to generate up to 84% NO(+).(H2O)n
      reactant ions in zero air. The change of the working gas from zero air to N2
      allows us to change the major reactant ions from NO(+).(H2O)n to H3O(+).(H2O)n.
      In this paper we present the description of the new CD-APCI and discuss the
      processes associated with the NO(+) formation. The selective formation of
      NO(+).(H2O)n reactant ions offers chemical ionization based on these ions which
      can be of great advantage for some classes of chemicals. We demonstrate here a
      significant increase in the sensitivity of the IMS-MS instrument for monoaromatic
      volatile organic compound (VOC) detection upon NO(+).(H2O)n chemical ionization. 

PMID- 24081309
TI  - Wide-field interferometric phase microscopy with molecular specificity using
      plasmonic nanoparticles.
AB  - We present a method for adding molecular specificity to wide-field
      interferometric phase microscopy (IPM) by recording the phase signatures of gold
      nanoparticles (AuNPs) labeling targets of interest in biological cells. The AuNPs
      are excited by time-modulated light at a wavelength corresponding to their
      absorption spectral peak, evoking a photothermal (PT) effect due to their
      plasmonic resonance. This effect induces a local temperature rise, resulting in
      local refractive index and phase changes that can be detected optically. Using a
      wide-field interferometric phase microscope, we acquired an image sequence of the
      AuNP sample phase profile without requiring lateral scanning, and analyzed the
      time-dependent profile of the entire field of view using a Fourier analysis,
      creating a map of the locations of AuNPs in the sample. The system can image a
      wide-field PT phase signal from a cluster containing down to 16 isolated AuNPs.
      AuNPs are then conjugated to epidermal growth factor receptor (EGFR) antibodies
      and inserted to an EGFR-overexpressing cancer cell culture, which is imaged using
      IPM and verified by confocal microscopy. To the best of our knowledge, this is
      the first time wide-field interferometric PT imaging is performed at the
      subcellular level without the need for total internal reflection effects or
      scanning.

PMID- 24081307
TI  - miR-34a expression, epigenetic regulation, and function in human placental
      diseases.
AB  - Preeclampsia (PE) is the major pregnancy-induced hypertensive disorder
      responsible for maternal and fetal morbidity and mortality that can be associated
      with intrauterine growth restriction (IUGR). PE and IUGR are thought to be due to
      a placental defect, occurring early during pregnancy. Several placental microRNAs
      (miRNAs) have been shown to be deregulated in the context of placental diseases
      and could thus play a role in the pathophysiology of PE. Here, we show that pri
      miR-34a is overexpressed in preeclamptic placentas and that its placental
      expression is much higher during the first trimester of pregnancy than at term,
      suggesting a possible developmental role. We explored pri-miR-34a regulation and
      showed that P53, a known activator of miR-34a, is reduced in all pathological
      placentas and that hypoxia can induce pri-miR-34a expression in JEG-3 cells. We
      also studied the methylation status of the miR-34a promoter and revealed
      hypomethylation in all preeclamptic placentas (associated or not with IUGR),
      whereas hypoxia induced a hypermethylation in JEG-3 cells at 72 h. Despite the
      overexpression of pri-miR-34a in preeclampsia, there was a striking decrease of
      the mature miR-34a in this condition, suggesting preeclampsia-driven alteration
      of pri-miR-34a maturation. SERPINA3, a protease inhibitor involved in placental
      diseases, is elevated in IUGR and PE. We show here that miR-34a overexpression in
      JEG-3 downregulates SERPINA3. The low level of mature miR-34a could thus be an
      important mechanism contributing to SERPINA3 upregulation in placental diseases.
      Overall, our results support a role for miR-34a in the pathophysiology of
      preeclampsia, through deregulation of the pri-miRNA expression and its altered
      maturation. 

PMID- 24081310
TI  - Nutrigenomics and cancer therapy.

PMID- 24081311
TI  - Synthesis and C2-functionalization of indoles with allylic acetates under rhodium
      catalysis.
AB  - Tandem rhodium-catalyzed oxidative allylation and annulation of acetanilides with
      allyl acetate to afford the corresponding indoles are described. In addition, the
      site-selective C2 allylation, crotylation and prenylation of indoles using
      allylic acetates under rhodium catalysis are reported. 

PMID- 24081312
TI  - Sublingual microcirculatory changes during transient intra-abdominal hypertension
      -a prospective observational study in laparoscopic surgery patients.
AB  - BACKGROUND: Microvascular alterations and intra-abdominal hypertension are both
      involved in development of organ failure. It is not known whether increased intra
      abdominal pressure (IAP) is associated with microcirculatory perfusion
      derangements. HYPOTHESIS: Transient increase in IAP induced by pneumoperitoneum
      affects sublingual microcirculation. METHODS: 16 laparoscopic cholecystectomy
      patients were studied. Sidestream dark field (SDF) imaging was used to evaluate
      sublingual microcirculation. Microcirculatory videos were done before surgery, at
      least 15 minutes after initiation of pneumoperitoneum and 1 hour after the
      pneumoperitoneum. Microcirculation cut-off value for vessels was 20 MUm. RESULTS:
      IAP was held at 12.6 (from 12 to 14) mmHg, mean (SD) duration of pneumoperitoneum
      was 41 (14) minutes. At the baseline, mean total vascular density was 18.8 (2.6)
      and perfused vessel density 13.2 (2.9) per mm2. Proportion of perfused vessels
      was 59 (11) % and microvascular flow index 2.2 (0.4). Median (IQR) heterogeneity
      index was 0.6 (0.4-0.9) and mean De Backer score 13.6 (1.5). Increase in IAP did
      not cause significant changes in sublingual microcirculatory parameters.
      CONCLUSIONS: Transiently increased IAP due to pneumoperitoneum does not affect
      sublingual microcirculatory blood flow and vessel density in patients undergoing
      laparoscopic surgery. However, the low proportion of perfused vessels indicates
      the prevalence of perioperative microcirculatory deficiency in these patients.

PMID- 24081313
TI  - An effect of glycoprotein IIb/IIIa inhibitors on the kinetics of red blood cells
      aggregation.
AB  - The reversible aggregation of red blood cells (RBCs) continues to be of the basic
      science and clinical interest. Recently it has been reported about a specific
      binding between fibrinogen and unknown erythrocyte glycoprotein receptors. The
      aim of this study was to investigate whether the red blood cell aggregation
      (RBCA) include the cell-cell interaction using the membrane receptors that bind
      such ligands as fibrinogen or fibronectin. To test this hypothesis the RBCs were
      incubated with monafram - the drug of the monoclonal antibodies against
      glycoprotein (GP) IIb/IIIa, with the GPIIb-IIIa receptor antagonist tirofiban,
      epifibatide and with the fibrinogen inhibiting peptide. It has been found that
      the RBC incubation with monafram resulted in a marked RBCA decrease mainly in
      persons with high level of aggregation. Another research session has shown that
      RBC incubation with fibronectin was accompanied by a significant RBCA rise. The
      monafram addition to red cell incubation medium resulted in a significant RBCA
      lowering. The cell incubation with tirofiban and epifibatide issued in RBCA
      decrease. The similar results were obtained when RBCs were incubated with the
      fibrinogen inhibiting peptide. Although monafram, tirofiban, eptifibatide and the
      fibrinogen inhibiting peptide were related to fibrinogen function they didn't
      inhibit RBCA completely. Therefore, under moderate and low red blood cell
      aggregation the cell binding is probably related to nonspecific mode. It seems
      evident that the specific and nonspecific modes of red blood cell aggregate
      formation could co-exist. Additional theoretical and experimental investigations
      in this area are needed. 

PMID- 24081314
TI  - Drugs for cognitive loss and dementia.
AB  - The drugs currently available for the treatment of Alzheimer's disease and other
      dementias can provide limited symptomatic improvement. The acetylcholinesterase
      inhibitors donepezil, rivastigmine, and galantamine and the NMDA-receptor
      antagonist memantine have produced modest but apparently persistent improvements
      in cognition, activities of daily living, and behavior in patients with disease
      severity ranging from mild to severe. Among the acetylcholinesterase inhibitors,
      transdermal rivastigmine causes fewer gastrointestinal side effects than the oral
      formulation. Whether adding memantine to an acetylcholinesterase inhibitor is
      more effective than an acetylcholinesterase inhibitor alone remains to be
      established; clinical trial results have been mixed. None of these agents have
      been shown to stop or reverse the underlying neurodegenerative process.

PMID- 24081315
TI  - Positive effects of the residual templates within the MCM-41 mesoporous silica
      channels in the metal-catalyzed reactions.
AB  - As-synthesized Pd/MCM-41 and Au/MCM-41 including the residual SDA organic
      templates, cetyltrimethylammonium bromide (CTABr), within the mesoporous channels
      exhibit superior catalytic activities than the conventionally calcined ones
      without templates, owing to the stabilizing effect of metal nanoparticles,
      concentration effect of organic substrates and co-catalyst effect due to the
      basic properties. 

PMID- 24081316
TI  - Synergistic self-assembly of scaffolds and building blocks for directed synthesis
      of organic nanomaterials.
AB  - Surfactants and hydrophobic monomers spontaneously assemble into vesicles
      containing monomers within the bilayer. The joint action of monomers and
      surfactants is essential in this synergistic self-assembly. Polymerization in the
      bilayer formed hollow polymer nanocapsules. 

PMID- 24081318
TI  - The role of recovery residences in promoting long-term addiction recovery.

PMID- 24081317
TI  - The macular pigment optical density spatial profile and increasing age.
AB  - PURPOSE: To investigate the relationship between the central spatial profile of
      macular pigment optical density (MPOD) and increasing age in normal eyes.
      METHODS: Ninety-eight individuals (aged 19-71 years) with good visual acuity,
      free from ocular disease, and with clear ocular media participated. MPOD was
      measured at 0.25, 0.50, 1.00, and 1.75 degrees  eccentricity from the foveal
      centre using a heterochromatic flicker photometry based densitometer instrument.
      RESULTS: Linear regression analysis revealed that there was no statistically
      significant association between MPOD and increasing age for the group as a whole
      at 0.25, 0.50, and 1.00 degrees  eccentricity (p > 0.05 for all eccentricities).
      There was a small but statistically significant positive association between
      increasing age and MPOD at 1.75 degrees  eccentricity (p = 0.020), but age only
      accounted for 6 % of the variation in MPOD values. Fifteen percent of all
      participants had a non-exponential MPOD spatial profile. CONCLUSION: There was no
      statistically significant relationship between MPOD and increasing age for three
      of the four locations measured. A significant proportion of individuals show an
      atypical MPOD spatial profile, indicating that studies on MPOD should ideally
      report information on the MPOD spatial profile rather than estimates from only
      one retinal location.

PMID- 24081319
TI  - Classroom peer relationships and behavioral engagement in elementary school: the
      role of social network equity.
AB  - Applying social capital and systems theories of social processes, we examine the
      role of the classroom peer context in the behavioral engagement of low-income
      students (N = 80) in urban elementary school classrooms (N = 22). Systematic
      child observations were conducted to assess behavioral engagement among second to
      fifth graders in the fall and spring of the same school year. Classroom
      observations, teacher and child questionnaires, and social network data were
      collected in the fall. Confirming prior research, results from multilevel models
      indicate that students with more behavioral difficulties or less academic
      motivation in the fall were less behaviorally engaged in the spring. Extending
      prior research, classrooms with more equitably distributed and interconnected
      social ties-social network equity-had more behaviorally engaged students in the
      spring, especially in classrooms with higher levels of observed organization
      (i.e., effective management of behavior, time, and attention). Moreover, social
      network equity attenuated the negative relation between student behavioral
      difficulties and behavioral engagement, suggesting that students with behavioral
      difficulties were less disengaged in classrooms with more equitably distributed
      and interconnected social ties. Findings illuminate the need to consider
      classroom peer contexts in future research and intervention focused on the
      behavioral engagement of students in urban elementary schools.

PMID- 24081320
TI  - Honeysuckle anthocyanin supplementation prevents diet-induced obesity in C57BL/6
      mice.
AB  - This study investigated the anti-obesity effects of honeysuckle anthocyanins (HA)
      in a high fat diet-induced mouse model. The mice were initially fed with a low
      fat diet (LFD) or high-fat diet (HFD) for 8 weeks. After that, the HFD-fed mice
      were divided into five groups, with 12 mice in each group, including a HFD group,
      a HFD plus Orlistat group, and three HFD plus HA (at a dose of 50, 100, or 200 mg
      kg(-1)) groups, for another 8-week experiment. HA at 100 or 200 mg kg(-1) can
      suppress body weight gain, reduce serum and liver lipid profiles, ameliorate
      impaired hepatic function, and significantly increase serum adiponectin
      concentration while decreasing serum insulin and leptin levels. These results
      suggest that the anti-obesity effect of HA might be through the blockage of lipid
      accumulation. 

PMID- 24081321
TI  - H2-dependent azoreduction by Shewanella oneidensis MR-1: involvement of secreted
      flavins and both [Ni-Fe] and [Fe-Fe] hydrogenases.
AB  - In this paper, the hydrogen (H2)-dependent discoloration of azo dye amaranth by
      Shewanella oneidensis MR-1 was investigated. Experiments with hydrogenase
      deficient strains demonstrated that periplasmic [Ni-Fe] hydrogenase (HyaB) and
      periplasmic [Fe-Fe] hydrogenase (HydA) are both respiratory hydrogenases of
      dissimilatory azoreduction in S. oneidensis MR-1. These findings suggest that
      HyaB and HydA can function as uptake hydrogenases that couple the oxidation of H2
      to the reduction of amaranth to sustain cellular growth. This constitutes to our
      knowledge the first report of the involvement of [Fe-Fe] hydrogenase in a
      bacterial azoreduction process. Assays with respiratory inhibitors indicated that
      a menaquinone pool and different cytochromes were involved in the azoreduction
      process. High-performance liquid chromatography analysis revealed that flavin
      mononucleotide and riboflavin were secreted in culture supernatant by S.
      oneidensis MR-1 under H2-dependent conditions with concentration of 1.4 and 2.4
      MUmol g protein(-1), respectively. These endogenous flavins were shown to
      significantly accelerate the reduction of amaranth at micromolar concentrations
      acting as electron shuttles between the cell surface and the extracellular azo
      dye. This work may facilitate a better understanding of the mechanisms of
      azoreduction by S. oneidensis MR-1 and may have practical applications for
      microbiological treatments of dye-polluted industrial effluents.

PMID- 24081322
TI  - Cloning Rosa hybrid phenylacetaldehyde synthase for the production of 2
      phenylethanol in a whole cell Escherichia coli system.
AB  - 2-Phenylethanol (2-PE) is a desirable compound in the food and perfumery
      industries with a characteristic rose fragrance. Until now, most of the studied
      biotechnological processes to produce 2-PE were conducted using natural 2-PE
      producing yeasts. Only several researches were conducted in other genetically
      engineered microorganisms that simulated the Ehrlich pathway for the conversion
      of amino acids to fusel alcohols. Here, a novel metabolic pathway has been
      designed in Escherichia coli to produce 2-PE, using the Rosa hybrid
      phenylacetaldehyde synthase (PAAS), a pyridoxal 5'-phosphate (PLP)-dependent
      enzyme capable of transforming L-phenylalanine (L-phe) into phenylacetaldehyde by
      decarboxylation and oxidation. To overcome the enzyme insolubility in E. coli,
      several plasmids and host strains were tested for their expression ability. The
      desired results were obtained by using the pTYB21 plasmid containing the intein
      tag from the Saccharomyces cerevisiae VMA1. It was discovered that the intein
      PAAS activity is temperature-dependent, working well in the range of 25 to 30 
      degrees C but losing most of its activity at 37  degrees C. When external PLP
      cofactor was added, the cells produced 0.39 g l-1 2-PE directly from L-phe. In
      addition, a biotransformation that was based only on internal de novo PLP
      synthesis produced 0.34 g l-1 2-PE, thus creating for the first time an E. coli
      strain that can produce 2-PE from L-phe without the need for exterior cofactor
      additions.

PMID- 24081323
TI  - Establishment of a soaking RNA interference and Bombyx mori nucleopolyhedrovirus
      (BmNPV)-hypersensitive cell line using Bme21 cell.
AB  - The double-stranded RNA (dsRNA) mediated RNA interference (RNAi) is widely
      employed in silkworm and its tissue-derived cell lines for gene function
      analysis. Baculovirus expression vector system (BEVS) has an advantage for large
      scale protein expression. Previously, combining these useful tools, we improved
      traditional AcMNPV-Sf9 BEVS to produce modified target glycoproteins, where the
      ectopic expression of Caenorhabditis elegans systemic RNAi defective-1 (SID-1)
      was found to be valuable for soaking RNAi. In current study, we applied CeSID-1
      protein to a Bombyx mori NPV (BmNPV)-hypersensitive Bme21 cell line and
      investigated its properties both in soaking RNAi ability and recombinant protein
      expression. The soaking RNAi-mediated suppression in the Bme21 cell enables us to
      produce modified glycoproteins of interest in BmNPV-Bme21 BEVS. 

PMID- 24081324
TI  - Positive affect in the family environment protects against relapse in first
      episode psychosis.
AB  - PURPOSE: To evaluate the contribution of positive affect in the family
      environment to relapse in first episode psychosis. METHOD: 65 service users with
      a first episode of psychosis were recruited into the current study along with
      their key relatives. Relatives were interviewed and rated using the Expressed
      Emotion (EE) measure of warmth, whilst service users completed questionnaires
      about the positive and negative affects that they perceived from the family
      environment. Associations between these measures and relapse were examined in a
      one-year prospective design. RESULTS: Service users were less likely to relapse
      within 6 and 12-month follow-up periods when their relatives were rated high on
      EE warmth, or when they perceived more positive affect from the family. The
      relationships between service users' perceived positive affect and relapse were
      preserved after controlling for baseline symptoms, substance use and employment
      status. Service users' perceptions of positive affect and EE ratings of warmth
      appeared to be stronger predictors of relapse outcome than criticism and other EE
      variables. CONCLUSIONS: Positive family environments may protect against relapse
      in first episode psychosis. Psychosocial interventions should aim to foster and
      maintain positive affect in families during the early stages of illness. Further
      research is needed to understand the mechanisms linking positive affect and
      outcomes for people recovering from psychosis.

PMID- 24081325
TI  - ADHD and the externalizing spectrum: direct comparison of categorical,
      continuous, and hybrid models of liability in a nationally representative sample.
AB  - PURPOSE: Alcohol use disorders, substance use disorders, and antisocial
      personality disorder share a common externalizing liability, which may also
      include attention-deficit hyperactivity disorder (ADHD). However, few studies
      have compared formal quantitative models of externalizing liability, with the aim
      of delineating the categorical and/or continuous nature of this liability in the
      community. This study compares categorical, continuous, and hybrid models of
      externalizing liability. METHOD: Data were derived from the 2004-2005 National
      Epidemiologic Survey on Alcohol and Related Conditions (N = 34,653). Seven
      disorders were modeled: childhood ADHD and lifetime diagnoses of antisocial
      personality disorder (ASPD), nicotine dependence, alcohol dependence, marijuana
      dependence, cocaine dependence, and other substance dependence. RESULTS: The
      continuous latent trait model provided the best fit to the data. Measurement
      invariance analyses supported the fit of the model across genders, with females
      displaying a significantly lower probability of experiencing externalizing
      disorders. Cocaine dependence, marijuana dependence, other substance dependence,
      alcohol dependence, ASPD, nicotine dependence, and ADHD provided the greatest
      information, respectively, about the underlying externalizing continuum.
      CONCLUSIONS: Liability to externalizing disorders is continuous and dimensional
      in severity. The findings have important implications for the organizational
      structure of externalizing psychopathology in psychiatric nomenclatures.

PMID- 24081326
TI  - Immune-modulation and properties of absorption and blood brain barrier
      permeability of 1,8-naphthyridine derivatives.
AB  - Considering the high selectivity at the cannabinoid CB2 receptor of recently
      designed 1,8-naphthyridine derivatives and the protective role of this receptor
      in neurological disorders, in this study we investigated the immune-modulatory
      and anti-inflammatory effects of these compounds as well as their potential
      properties of intestinal absorption and blood-brain barrier (BBB) permeability.
      We used peripheral blood mononuclear cells (PBMC) known to express the CB2
      receptor. We observed that test compounds, CB13, CB82 and CB91 reduced PBMC
      proliferation. The anti-proliferative effect of CB13 and CB91 was partially
      mediated by the CB2 receptor. These compounds blocked the cells cycle and CB91
      reduced T cell activation. CB82 and CB91 down-regulated the expression of
      phosphorylated proteins like NF-kappaB, ERK, Akt and the enzyme Cox-2, CB91
      blocked the expression of the CB2 receptor and its inhibitory effect was CB2
      receptor mediated. We also investigated CB91 properties of intestinal absorption
      and BBB permeability in order to suggest its potential efficacy on the
      infiltrating auto-reactive lymphocytes at the level of the central nervous
      system. For this purpose, CB91 was tested in drug-permeability assays on Caco-2
      cells to evaluate its oral bioavailability and on MDCKII-hMDR1 cells to estimate
      its BBB permeability. The results indicated that this compound possesses medium
      level of intestinal absorption and BBB permeability. Our data suggest that CB91,
      modulating the immune response by CB2 receptor mediated mechanism and showing
      medium level of intestinal absorption and BBB permeability, might be developed as
      a potential orally delivered drug and might find potential application in
      pathologies like multiple sclerosis. 

PMID- 24081327
TI  - Genetic variation in the vitamin D receptor, plasma 25-hydroxyvitamin D, and
      biomarkers of cardiometabolic disease in Caucasian young adults.
AB  - BACKGROUND/AIMS: Vitamin D regulates gene transcription by binding to the vitamin
      D receptor (VDR), potentially affecting cardiometabolic disease risk. However,
      studies of 25-hydroxyvitamin D [25(OH)D] and cardiometabolic disease are
      inconsistent. Inconsistencies may result from unaccounted for interactions
      between VDR genetic variants and 25(OH)D. We examined the effect of 25(OH)D on
      the association between VDR variants and cardiometabolic disease biomarkers.
      METHODS: The relationship between 25(OH)D, 24 VDR variants, and 10
      cardiometabolic biomarkers was examined in 488 Caucasians aged 20-29 years.
      Covariate-adjusted general linear models were used to examine the interaction
      effect of 25(OH)D * VDR on each biomarker. When interactions were significant (p
      < 0.05), relationships were further examined with analysis of covariance,
      stratified by tertiles of 25(OH)D and adjusted for multiple comparisons. RESULTS:
      In the lowest tertile of 25(OH)D, major allele homozygotes for rs3819545 had
      higher insulin and HOMA-IR than minor allele carriers (p <= 0.002). Fasting
      insulin and HOMA-IR were lower in the highest than the lowest tertile of 25(OH)D
      among major allele homozygotes (p < 0.0001), but minor allele carriers had
      similar levels regardless of vitamin D status. CONCLUSIONS: We identified 25(OH)D
      dependent associations between rs3819545 and glycemic dysregulation biomarkers.
      Major allele homozygotes with low vitamin D status may be at increased risk of
      insulin resistance.

PMID- 24081328
TI  - Akt switches TopBP1 function from checkpoint activation to transcriptional
      regulation through phosphoserine binding-mediated oligomerization.
AB  - Our previous study showed that Akt phosphorylates TopBP1 at the Ser-1159 residue
      and induces its oligomerization. Oligomerization is required for TopBP1 to bind
      and repress E2F1 activity. However, the mechanism through which phosphorylation
      of TopBP1 by Akt leads to its oligomerization remains to be determined. Here, we
      demonstrate that binding between the phosphorylated Ser-1159 (pS1159) residue and
      the 7th and 8th BRCT domains of TopBP1 mediates TopBP1 oligomerization. Mutations
      within the 7th and 8th BRCT domains of TopBP1 that block binding to a pS1159
      containing peptide block TopBP1 oligomerization and its ability to bind and
      repress E2F1 activities. The Akt-induced TopBP1 oligomerization is also directly
      demonstrated in vitro by size exclusion chromatography. Importantly,
      oligomerization perturbs the checkpoint-activating function of TopBP1 by
      preventing its recruitment to chromatin and ATR binding upon replicative stress.
      Hyperactivation of Akt inhibits Chk1 phosphorylation after hydroxyurea treatment,
      and this effect is dependent on TopBP1 phosphorylation at Ser-1159. Thus, Akt can
      switch the TopBP1 function from checkpoint activation to transcriptional
      regulation by regulating its quaternary structure. This pathway of regulation is
      clinically significant, since treatment of a specific Akt inhibitor in PTEN
      mutated cancer cells inhibits TopBP1 oligomerization and causes its function to
      revert from promoting survival to checkpoint activation. 

PMID- 24081329
TI  - Poly(A) tail-mediated gene regulation by opposing roles of Nab2 and Pab2 nuclear
      poly(A)-binding proteins in pre-mRNA decay.
AB  - The 3' end of most eukaryotic transcripts is decorated by poly(A)-binding
      proteins (PABPs), which influence the fate of mRNAs throughout gene expression.
      However, despite the fact that multiple PABPs coexist in the nuclei of most
      eukaryotes, how functional interplay between these nuclear PABPs controls gene
      expression remains unclear. By characterizing the ortholog of the Nab2/ZC3H14
      zinc finger PABP in Schizosaccharomyces pombe, we show here that the two major
      fission yeast nuclear PABPs, Pab2 and Nab2, have opposing roles in
      posttranscriptional gene regulation. Notably, we find that Nab2 functions in gene
      specific regulation in a manner opposite to that of Pab2. By studying the
      ribosomal-protein-coding gene rpl30-2, which is negatively regulated by Pab2 via
      a nuclear pre-mRNA decay pathway that depends on the nuclear exosome subunit
      Rrp6, we show that Nab2 promotes rpl30-2 expression by acting at the level of the
      unspliced pre-mRNA. Our data support a model in which Nab2 impedes Pab2/Rrp6
      mediated decay by competing with Pab2 for polyadenylated transcripts in the
      nucleus. The opposing roles of Pab2 and Nab2 reveal that interplay between
      nuclear PABPs can influence gene regulation. 

PMID- 24081330
TI  - Cessation of epithelial Bmp signaling switches the differentiation of crown
      epithelia to the root lineage in a beta-catenin-dependent manner.
AB  - The differentiation of dental epithelia into enamel-producing ameloblasts or the
      root epithelial lineage compartmentalizes teeth into crowns and roots. Bmp
      signaling has been linked to enamel formation, but its role in root epithelial
      lineage differentiation is unclear. Here we show that cessation of epithelial Bmp
      signaling by Bmpr1a depletion during the differentiation stage switched
      differentiation of crown epithelia into the root lineage and led to formation of
      ectopic cementum-like structures. This phenotype is related to the upregulation
      of Wnt/beta-catenin signaling and epithelial-mesenchymal transition (EMT).
      Although epithelial beta-catenin depletion during the differentiation stage also
      led to variable enamel defect and precocious/ectopic formation of fragmented root
      epithelia in some teeth, it did not cause ectopic cementogenesis and inhibited
      EMT in cultured dental epithelia. Concomitant epithelial beta-catenin depletion
      rescued EMT and ectopic cementogenesis caused by Bmpr1a depletion. These data
      suggested that Bmp and Wnt/beta-catenin pathways interact antagonistically in
      dental epithelia to regulate the root lineage differentiation and EMT. These
      findings will aid in the design of new strategies to promote functional
      differentiation in the regeneration and tissue engineering of teeth and will
      provide new insights into the dynamic interactions between the Bmp and Wnt/beta
      catenin pathways during cell fate decisions. 

PMID- 24081331
TI  - The yeast AMPK homolog SNF1 regulates acetyl coenzyme A homeostasis and histone
      acetylation.
AB  - Acetyl coenzyme A (acetyl-CoA) is a key metabolite at the crossroads of
      metabolism, signaling, chromatin structure, and transcription. Concentration of
      acetyl-CoA affects histone acetylation and links intermediary metabolism and
      transcriptional regulation. Here we show that SNF1, the budding yeast ortholog of
      the mammalian AMP-activated protein kinase (AMPK), plays a role in the regulation
      of acetyl-CoA homeostasis and global histone acetylation. SNF1 phosphorylates and
      inhibits acetyl-CoA carboxylase, which catalyzes the carboxylation of acetyl-CoA
      to malonyl-CoA, the first and rate-limiting reaction in the de novo synthesis of
      fatty acids. Inactivation of SNF1 results in a reduced pool of cellular acetyl
      CoA, globally decreased histone acetylation, and reduced fitness and stress
      resistance. The histone acetylation and transcriptional defects can be partially
      suppressed and the overall fitness improved in snf1Delta mutant cells by
      increasing the cellular concentration of acetyl-CoA, indicating that the
      regulation of acetyl-CoA homeostasis represents another mechanism in the SNF1
      regulatory repertoire. 

PMID- 24081333
TI  - Introducing a new series: Giants in chest medicine.

PMID- 24081332
TI  - The MLL3/MLL4 branches of the COMPASS family function as major histone H3K4
      monomethylases at enhancers.
AB  - Histone H3 lysine 4 (H3K4) can be mono-, di-, and trimethylated by members of the
      COMPASS (complex of proteins associated with Set1) family from Saccharomyces
      cerevisiae to humans, and these modifications can be found at distinct regions of
      the genome. Monomethylation of histone H3K4 (H3K4me1) is relatively more enriched
      at metazoan enhancer regions compared to trimethylated histone H3K4 (H3K4me3),
      which is enriched at transcription start sites in all eukaryotes. Our recent
      studies of Drosophila melanogaster demonstrated that the Trithorax-related (Trr)
      branch of the COMPASS family regulates enhancer activity and is responsible for
      the implementation of H3K4me1 at these regions. There are six COMPASS family
      members in mammals, two of which, MLL3 (GeneID 58508) and MLL4 (GeneID 8085), are
      most closely related to Drosophila Trr. Here, we use chromatin
      immunoprecipitation-sequencing (ChIP-seq) of this class of COMPASS family members
      in both human HCT116 cells and mouse embryonic stem cells and find that MLL4 is
      preferentially found at enhancer regions. MLL3 and MLL4 are frequently mutated in
      cancer, and indeed, the widely used HCT116 cancer cell line contains inactivating
      mutations in the MLL3 gene. Using HCT116 cells in which MLL4 has also been
      knocked out, we demonstrate that MLL3 and MLL4 are major regulators of H3K4me1 in
      these cells, with the greatest loss of monomethylation at enhancer regions.
      Moreover, we find a redundant role between Mll3 (GeneID 231051) and Mll4 (GeneID
      381022) in enhancer H3K4 monomethylation in mouse embryonic fibroblast (MEF)
      cells. These findings suggest that mammalian MLL3 and MLL4 function in the
      regulation of enhancer activity and that mutations of MLL3 and MLL4 that are
      found in cancers could exert their properties through malfunction of these
      Trr/MLL3/MLL4-specific (Trrific) enhancers. 

PMID- 24081334
TI  - Guidelines and conflicts: a new twist.

PMID- 24081335
TI  - The return of FEV3.

PMID- 24081336
TI  - Maintenance programs after pulmonary rehabilitation: how may we advance this
      field?

PMID- 24081337
TI  - Public policy, air quality, and protecting the most vulnerable.

PMID- 24081339
TI  - Point: Should antipyretic therapy be given routinely to febrile patients in
      septic shock? Yes.

PMID- 24081343
TI  - Introducing giants in chest medicine: Alfred Soffer, MD, Master FCCP.

PMID- 24081340
TI  - Counterpoint: Should antipyretic therapy be given routinely to febrile patients
      in septic shock? No.

PMID- 24081344
TI  - Will my job be safe if I defend my patients? When patient advocacy collides with
      employment law.
AB  - Physicians are moving increasingly from self-employed, private practices to at
      will employment relationships. This historic change in the organizational
      administration of medical services is likely to accelerate as the Affordable Care
      Act is implemented and as accountable care organizations permeate the medical
      marketplace. Physicians vow an ascendant oath to safeguard patients' welfare, but
      as they become employees, they may sign legal contracts that also oblige
      obedience to the institutions that hire them. What happens when an employer makes
      a decision that is not in the best interests of patients and the physicians
      fulfill their Hippocratic obligation to voice dissent on their patients' behalf
      rather than abiding by their contractual obligation to obey their employer? This
      article explores the philosophical and legal ramifications of this potential
      collision of obligations to patients and to employers. 

PMID- 24081345
TI  - Nutrition as a metabolic modulator in COPD.
AB  - COPD is an important global health problem. In addition to pulmonary impairment,
      systemic inflammation, musculoskeletal abnormalities, and cardiovascular
      comorbidity influence disease burden and mortality risk. Body weight and body
      composition are important discriminants in classifying disease heterogeneity. The
      rationale for and efficacy of caloric supplementation in preventing and treating
      involuntary weight loss is currently well established. For maintenance of muscle
      and bone tissue, appropriately timed, high-quality protein intake and addressing
      vitamin D deficiency must be considered. Specific nutrients (eg, n-3
      polyunsaturated fatty acids and polyphenolic compounds) may have the
      pharmacologic potential to boost decreased muscle mitochondrial metabolism and
      enhance impaired physical performance, particularly when the metabolic stimulus
      of physical activity alone is limited. At this stage, evidence is insufficient to
      support an intake of high doses of single nutritional supplements to modulate
      respiratory pathology, but some small studies have identified micronutrient
      modulation via the diet as a promising intervention. 

PMID- 24081347
TI  - Evaluating the safety of COPD medications: an evidence-based review.
AB  - The goals of management of COPD include reducing exposure to risk factors;
      improving lung function, exercise tolerance, and quality of life; and decreasing
      exacerbations and mortality. Pharmacologic treatments, such as inhaled beta2
      agonists, anticholinergics, and inhaled corticosteroids, are widely used to help
      achieve these goals. In addition to efficacy, medication safety is an important
      consideration in selecting COPD treatments. Clinical trials conducted in support
      of the regulatory review and approval process establish the general efficacy and
      tolerability of pharmacologic treatments for COPD, and these data are reflected
      in product labeling. Following approval, further research continues to provide
      more data with longer follow-up and in broader settings than feasible in clinical
      trials. These data add to our knowledge of the efficacy of medications.
      Understanding medication safety requires assessment of the quality and
      appropriateness of study design, as well as knowledge of study findings, and is
      of paramount importance in making sound clinical judgments in the treatment of
      patients with COPD. In recent years, a wealth of data on COPD medications has
      been published from different sources, including randomized clinical trials, meta
      analyses, systematic reviews, and observational studies. This review discusses
      important considerations in interpreting data from different types of studies,
      summarizes the tolerability profile of COPD medications established in
      preapproval studies, and discusses new findings from more recent postapproval
      data. 

PMID- 24081348
TI  - Using risk contracting to reduce service use, improve quality, and strengthen
      primary care.
AB  - The high costs of American health care, the related problem of the uninsured, and
      the grim fiscal prognosis of Medicare and Medicaid are among the most pressing
      challenges facing the United States today. A solution to the cost problem that
      does not reduce access or quality is sought by those at all points on the
      political spectrum. This article discusses the experience of an independent
      practice association that has collaborated with a related business partner and a
      health plan to improve the quality of care of 16,000 Medicare Advantage
      beneficiaries while substantially reducing hospitalization rates and overall
      service use. The capacity to reduce service use frees funds that are used to
      support the infrastructure for high-value care and to reward those who provide
      it. Higher performing primary care, supported by changes in payment, has driven a
      sustainable business model that preserves the option of independent practice for
      physicians. We are now testing competencies developed for Medicare Advantage in
      the Pioneer Accountable Care Organization program, which preserves the broad
      patient choice that is an important feature of traditional Medicare. 

PMID- 24081346
TI  - Systemic sclerosis-associated pulmonary arterial hypertension.
AB  - Pulmonary arterial hypertension (PAH) is the leading cause of death in systemic
      sclerosis (SSc) and affects up to 12% of all patients with SSc, with a 50%
      mortality rate within 3 years of PAH diagnosis. Compared with the idiopathic form
      of PAH (IPAH), patients with SSc-associated PAH (SSc-PAH) have a threefold
      increased risk of death and may receive a diagnosis late in the course of disease
      because of insidious onset and the high prevalence of cardiac, musculoskeletal,
      and pulmonary parenchymal comorbidities. Treatment with conventional forms of PAH
      therapy often yield poor results compared with IPAH cohorts; unfortunately, the
      exact reasons behind this remain poorly understood but likely include variations
      in the pathologic mechanisms, differences in cardiovascular response to
      increasing afterload, and inadequate strategies to detect and treat SSc-PAH early
      in its course. Current methods for screening and longitudinal evaluation of SSc
      PAH, such as the 6-min walk test, transthoracic echocardiography, and MRI, each
      have notable advantages and disadvantages. We provide an up-to-date, focused
      review of SSc-PAH and how it differs from IPAH, including pathogenesis,
      appropriate screening for disease onset, and new approaches to treatment and
      longitudinal assessment of this disease. 

PMID- 24081349
TI  - Normalization of sweat chloride concentration and clinical improvement with
      ivacaftor in a patient with cystic fibrosis with mutation S549N.
AB  - The cystic fibrosis (CF) protein forms an anion channel in epithelial cells, and
      the absence or defective function of this channel results in the clinical
      manifestations of CF. CF is an autosomal recessive disorder, and its many disease
      causing mutations divide into five or six classes. There are 10 known class 3
      gating mutations, the most common of which is G551D. Ivacaftor is a drug that in
      vitro increases open time and transepithelial chloride transport in all 10 gating
      mutations, but it is approved for use only in patients with the G551D mutation.
      We report complete normalization of sweat chloride concentration and rapid
      clinical improvement over 6 weeks of treatment with ivacaftor in a patient with
      CF with the gating mutation S549N. The findings suggest that ivacaftor should be
      considered for use in patients with any of the known gating mutations. 

PMID- 24081350
TI  - Periodic breathing with no heart beat.
AB  - A protocol was originally designed to study breathing control during and
      following cardiac arrest in humans, taking advantage of the period of pulseless
      ventricular fibrillation (PVF) produced while testing a newly implanted
      cardioverter-defibrillator device. A patient aged in his 60s with New York Heart
      Association class III heart failure (HF) (left ventricular ejection fraction of
      25%) who was originally part of this study displayed permanent periodic breathing
      (PB) and was then excluded from the final data analysis; his response is
      presented in this report. The 8- to 9-s PVF was incidentally produced during the
      ascending phase of a PB cycle, followed by another 12-s recovery period of low
      BP. PVF and its recovery had no effect on PB characteristics (period or
      amplitude). This occurred despite a profound change in Paco2, cerebral blood
      flow, and perfusion of the carotid bodies. It is concluded that PB in patients
      with HF could be produced by primary oscillations originating from the central
      pattern generator. 

PMID- 24081351
TI  - Chronic disorders of consciousness following coma: Part one: medical issues.
AB  - Increasing numbers of patients survive traumatic brain injury (TBI) and
      cardiopulmonary arrest and resuscitation and are admitted to the ICU in coma.
      Some of these patients become brain dead; others regain consciousness. Still
      others become vegetative or minimally conscious, conditions called chronic
      disorders of consciousness and ultimately are cared for outside the ICU. Comatose
      patients lack the wakefulness and awareness that distinguish consciousness from
      unconsciousness. Vegetative patients are awake in that they manifest sleep-wake
      cycles, but they are unaware of their environment and cannot respond to stimuli.
      Minimally conscious patients are awake, aware to a limited extent, and somewhat
      responsive. The diagnosis of the vegetative and minimally conscious states has
      been based largely on their behavioral and pathologic features, and it has been
      believed that vegetative patients remain in that condition permanently.
      Nevertheless, EEG and neuroimaging studies suggest that the traditional
      diagnostic approach is imprecise. Moreover, clinical investigations have revealed
      that some vegetative patients can become minimally conscious and that some
      minimally conscious patients can gain increased awareness. Few therapies for
      patients with chronic disorders of consciousness have been subjected to
      randomized trials. Furthermore, although a small number of patients have improved
      neurologically with or without treatment, their overall prognosis for neurologic
      recovery remains poor. 

PMID- 24081352
TI  - Chronic disorders of consciousness following coma: Part two: ethical, legal, and
      social issues.
AB  - Increasing numbers of patients survive traumatic brain injury and cardiopulmonary
      arrest and resuscitation and are admitted to the ICU while in coma. Some of these
      patients become brain dead; others regain consciousness. Still others become
      vegetative or minimally conscious, conditions called chronic disorders of
      consciousness and ultimately can be cared for outside the ICU. Whether these
      patients would want life-sustaining therapy is difficult to determine because
      most have not articulated their wishes before becoming comatose. Ethics and law
      recognize that patients with decision-making capacity have a right to refuse such
      therapy and that surrogates can exercise this right for them through the
      principle of substituted judgment as was established by the Supreme Court of New
      Jersey in the case of Karen Ann Quinlan. In its decision regarding Nancy Cruzan,
      the US Supreme Court determined that states may require clear and convincing
      evidence of a vegetative patient's prior wishes before life-sustaining therapy
      may be withdrawn; this standard has been applied to minimally conscious patients
      by state supreme courts in some cases. Nevertheless, cases such as these only
      come to the legal system because end-of-life decisions are contested, which is
      unusual, and most end-of-life decisions for specific patients with chronic
      disorders of consciousness are made by surrogates with recommendations from
      physicians without court involvement. Recent advances in neuroimaging may
      influence both end-of-life decision-making and legal deliberations. Targeting
      vegetative and minimally conscious patients in medical resource allocation
      remains ethically unacceptable and untested in the law. 

PMID- 24081353
TI  - Air travel: effects of sleep deprivation and jet lag.
AB  - Air travel is a common mode of transportation in today's society, particularly
      for individuals traveling long distances. Sleep disturbances associated with air
      travel frequently result in cognitive and physiologic impairments that may be
      detrimental to the traveler's experience and intent. A primary consequence of air
      travel is the development of acute sleep deprivation, which may result in reduced
      attention/vigilance, alteration in mood states, diminished memory processing, and
      alteration in executive function. Along with and contributing to acute sleep
      deprivation, circadian rhythm misalignment resulting in jet lag disorder (JLD) is
      frequently encountered by air travelers traversing multiple time zones. JLD is
      characterized by insomnia or excessive daytime sleepiness associated with
      physical or mental impairment associated with travel. This review focuses on the
      neurocognitive manifestations of acute sleep deprivation and the pathophysiology
      and treatment of JLD to provide the practicing clinician a greater understanding
      of the sleep abnormalities manifest in air travelers. Treatment recommendations
      for the traveler, including the use of light/melatonin therapy, sleep scheduling,
      and pharmacologic aids for both sleep and alertness, are provided. 

PMID- 24081354
TI  - Recurrent dyspnea following a swollen leg in a 46-year-old man.

PMID- 24081355
TI  - A 22-year-old woman with bronchiectasis and a mediastinal mass.

PMID- 24081356
TI  - A 48-year-old woman with headache and respiratory failure.

PMID- 24081359
TI  - Response.

PMID- 24081361
TI  - Targeted CT image screening and its effect on lung cancer detection rate.

PMID- 24081360
TI  - Understanding the relationship between sweat chloride and lung function in cystic
      fibrosis.

PMID- 24081362
TI  - Response.

PMID- 24081363
TI  - Sleep-disordered breathing and postoperative outcomes: patient safety first!

PMID- 24081364
TI  - Response.

PMID- 24081365
TI  - Response.

PMID- 24081366
TI  - Chasing down the acid-fast bacilli during treatment: need better yardsticks.

PMID- 24081367
TI  - Interruption of warfarin anticoagulation for dental surgery.

PMID- 24081368
TI  - Response.

PMID- 24081369
TI  - Response.

PMID- 24081370
TI  - Echocardiography in pulmonary hypertension.

PMID- 24081372
TI  - A 44-year-old man with progressive shortness of breath and left-sided pleuritic
      chest pain.

PMID- 24081373
TI  - A head-to-head comparison of periprocedural coagulability under anticoagulation
      with rivaroxaban versus dabigatran in patients undergoing ablation of atrial
      fibrillation.
AB  - BACKGROUND AND OBJECTIVES: Two new oral anticoagulants, rivaroxaban and
      dabigatran, with no need for anticoagulation monitoring, are available for
      patients with atrial fibrillation (AF). We aimed to compare their anticoagulant
      effects and safety when used during the AF ablation periprocedural period.
      METHODS: Patients undergoing AF ablation were randomly assigned to receive
      rivaroxaban 15 mg once daily (N = 30) or dabigatran 110 mg twice daily (N = 30).
      Rivaroxaban was withheld on the morning of the day before the ablation, and
      dabigatran was discontinued from the evening of the day before the procedure.
      Both anticoagulants were then resumed after haemostasis of the access site. D
      dimer levels were measured just before the ablation, at the end of the ablation,
      and at 24 h and 48 h after the procedure. RESULTS: The baseline D-dimer levels
      were identical in both groups. However, D-dimer levels increased more markedly
      following the ablation procedure in patients receiving rivaroxaban than in those
      receiving dabigatran (mean +/- standard deviation from 0.62 +/- 0.16 to 1.09 +/-
      0.38 MUg/mL vs from 0.59 +/- 0.08 to 0.75 +/- 0.17 MUg/mL; p < 0.0001). The rate
      of rebleeding from the access site was similar in patients receiving rivaroxaban
      and those receiving dabigatran (33 vs 27%; p = 0.78). CONCLUSION: As compared
      with dabigatran, rivaroxaban may increase the risk of hypercoagulability when
      used during the periprocedural period of AF ablation, suggesting a potential
      rebound effect of rivaroxaban or a mismatch between its half-life and dose
      regimen.

PMID- 24081374
TI  - Randomized, vitamin E-controlled trial of bicyclol plus metformin in non
      alcoholic fatty liver disease patients with impaired fasting glucose.
AB  - BACKGROUND: Non-alcoholic fatty liver disease (NAFLD) is associated with a high
      morbidity in patients with impaired fasting glucose (IFG). Bicyclol is a
      synthetic compound known to protect the liver against oxidation and lipid
      injuries. OBJECTIVE: The objective of this study was to evaluate the efficacy and
      safety of metformin and bicyclol in the treatment of NAFLD patients with IFG.
      METHODS: After lifestyle changes and metformin treatment (500 mg orally three
      times daily), the 248 patients enrolled with NAFLD and IFG were equally
      randomized to two 24-week treatment groups: bicyclol 25 mg three times daily or
      vitamin E (alpha-tocopherol) 100 mg three times daily (control). Anthropometric
      measurements, serum biochemistry, liver/spleen computed tomography ratio, and
      changes in liver histological parameters were compared before and after
      treatments. RESULTS: A total of 223 patients completed the treatment, and there
      were significant improvements in body mass index, waist-to-hip ratio, and
      biochemical parameters in both groups (P < 0.01). Compared with the control
      group, the improvement in serum alanine aminotransferase levels in the bicyclol
      group was statistically significant (P < 0.01). Liver histological assessments
      revealed that steatosis, inflammation, hepatocellular ballooning, and NAFLD
      activity scores (NAS) were all decreased in both groups after treatment (P <
      0.01). However, decreases in inflammation and NAS in the bicyclol group were
      statistically significant compared with the vitamin E group (P < 0.01). Adverse
      events in the bicyclol and control groups occurred in 1.79 and 1.80 %,
      respectively. CONCLUSION: Metformin combined with bicyclol is effective and safe
      in the treatment of patients with NAFLD and IFG. However, further studies with a
      larger sample size are needed to confirm the efficacy and safety of the
      combination.

PMID- 24081375
TI  - Differential expression of neuroblastoma cellular proteome due to AICD
      overexpression.
AB  - Amyloid-beta protein precursor intracellular domain (AICD), which exerts
      intracellular effects by interacting with proteins involved in a plethora of
      biological processes, is a key player behind the pathophysiology of Alzheimer's
      disease (AD). Keeping in mind that overwhelming presence of AICD would mimic AD
      like conditions in neuroblastoma cell lines, we hypothesized alteration in the
      proteomic expression pattern in these cells in the presence of AICD compared to
      their normal proteome. The rationale behind the study was to distinguish between
      symptomatic pathophysiological effects as opposed to any artifactual consequence
      due to protein overload in the cell lines. Using 2D-DIGE analysis and MALDI-MS
      identifications in neuro2A (mouse) and SHSY5Y (human) cell lines, we have
      identified several proteins belonging to different functional classes and
      involved in several biological pathways including protein folding, cytoskeletal
      dynamics, metabolism, and stress. Many of these were being upregulated or
      downregulated due to AICD effects and could be correlated directly with AD
      phenotypes. 

PMID- 24081377
TI  - The role of ABCA1 gene sequence variants on risk of Alzheimer's disease.
AB  - The ATP-binding cassette, sub-family A, member 1 gene (ABCA1) is a candidate risk
      gene for late onset Alzheimer's disease (LOAD) as a consequence of its role in
      cholesterol transport and metabolism, which is implicated in LOAD risk. ABCA1 has
      been shown in mouse models to enable the clearance of amyloid-beta peptide from
      the brain, through its role in the lipidation of apolipoprotein (APOE). Although
      recent large scale genome wide association studies (GWAS) have failed to find
      significant associations with common genetic variants in this gene and LOAD, rare
      variants in ABCA1 have been shown to influence plasma high-density lipoprotein
      cholesterol levels. Using next generation sequencing of pooled DNA samples, we
      sequenced all the coding regions of ABCA1 in 311 LOAD cases and 360 control
      individuals drawn from the Greek population to identify low frequency non
      synonymous variation. There were a significantly higher proportion of rare non
      synonymous variants in control individuals compared to AD cases, suggestive of a
      protective effect. These findings provide new evidence of an effect of ABCA1
      variants on AD risk. In addition they highlight the importance of high throughput
      sequencing in the identification of rare variation undetected by GWAS, but with
      the potential to have a strong effect on risk of LOAD. 

PMID- 24081376
TI  - Noradrenergic sympathetic sprouting and cholinergic reinnervation maintains non
      amyloidogenic processing of AbetaPP.
AB  - Alzheimer's disease (AD) is characterized by amyloid-beta (Abeta) plaques,
      hyperphosphorylated tau neurofibrillary tangles, and cholinergic dysfunction.
      Cholinergic degeneration can be mimicked in rats by lesioning medial septum
      cholinergic neurons. Hippocampal cholinergic denervation disrupts retrograde
      nerve growth factor (NGF) transport, leading to its accumulation, which
      subsequently triggers sprouting of noradrenergic sympathetic fibers from the
      superior cervical ganglia into hippocampus. Previously we reported that
      coincident with noradrenergic sprouting is the partial reinnervation of
      hippocampus with cholinergic fibers and the maintenance of a M1 muscarinic
      acetylcholine receptor (M1 mAChR) dependent long-term depression at CA3-CA1
      synapses that is lost in the absence of sprouting. These findings suggest that
      sympathetic sprouting and the accompanying cholinergic reinnervation maintains M1
      mAChR function. Importantly, noradrenergic sympathetic and cholinergic sprouting
      have been demonstrated in human postmortem AD hippocampus. Furthermore, M1 mAChRs
      are a recent focus as a therapeutic target for AD given their role in cognition
      and non-amyloidogenic processing of amyloid-beta protein precursor (AbetaPP).
      Here we tested the hypotheses that noradrenergic sympathetic sprouting is
      triggered by NGF, that sprouting maintains non-amyloidogenic AbetaPP processing,
      and that sprouting is prevented by intrahippocampal Abeta42 infusion. We found
      that NGF stimulates sprouting, that sprouting maintains non-amyloidogenic AbetaPP
      processing, and that Abeta42 is not only toxic to central cholinergic fibers
      innervating hippocampus but it prevents and reverses noradrenergic sympathetic
      sprouting and the accompanying cholinergic reinnervation. These findings
      reiterate the clinical implications of sprouting as an innate compensatory
      mechanism and emphasize the importance of M1 mAChRs as an AD therapeutic target. 

PMID- 24081379
TI  - Risk factors for development of dementia in a unique six-year cohort study. I. An
      exploratory, pilot study of involvement of the E4 allele of apolipoprotein E,
      mutations of the hemochromatosis-HFE gene, type 2 diabetes, and stroke.
AB  - Risk factors for dementia development are not well-defined. We evaluated several
      factors alone and in combination in a unique cohort of Caucasian volunteers over
      an approximately 6-year observation window using a nested case/control design.
      Factors included: apolipoprotein E (ApoE) gene variants (the E4 allele is the
      strongest confirmed genetic predisposing factor for Alzheimer's disease), the
      hemochromatosis-HFE gene mutations (H63D and C282Y), diabetes, and stroke. At
      study entry, subjects were >=65 years of age (M +/- SD = 73.0 +/- 4.9), had an
      MMSE score >=24, and no evidence of cerebrovascular disease or current
      depression. Genotyping was completed on 163 available DNA samples from three
      different groups at the study end: those who still had normal cognitive function;
      those who had developed dementia; and those with Mild Cognitive Impairment (MCI).
      Analyses were interpreted at the 95% confidence level without Bonferroni
      corrections. In the subgroup with dementia, all cases of diabetes were type 2 and
      present at study entry, whereas all strokes occurred during the study. The
      results highlight apparently synergistic interactions between genetic and medical
      risk factors for dementia development, gender differences in risk factors, and
      involvement of HFE mutations. Having E4 (i.e., either of E3/4 or E4/4), C282Y,
      H63D, diabetes, or stroke alone did not attain significance. Significant
      predisposing factors with post-hoc power >=80% were: E4 homozygosity
      (E4/4)males+females, odds ratio (OR) = 56.0); E4+diabetes (males+females, OR =
      13.7; E4+H63D+diabetes (females, OR = 52.0); E4+stroke (males, OR = 46.5). The
      importance of preventing diabetes and stroke to ward off dementia and the
      possible role of iron dysmetabolism in dementia are discussed. 

PMID- 24081380
TI  - Retrospective assessment of exposure to static magnetic fields during production
      and development of magnetic resonance imaging systems.
AB  - At present, the relationship between chronic exposure to static magnetic fields
      (SMF) and health effects is unclear. We developed a task-based deterministic
      model for estimating historical electromagnetic field exposure from the static B
      field (B0) of magnetic resonance imaging (MRI) systems, for a cohort of employees
      working at an MRI systems development and production facility. Technical maps
      describing the spatial distribution of fringe fields of B0 surrounding different
      types of MRI systems of various core strengths were exploited to derive estimates
      of static B0 exposure as a function of distance from the bore of the MRI system.
      Detailed information on tasks performed per exposed job and other model
      determinants were acquired through face-to-face interviews and used to derive
      base estimates of most recent exposure (2009) for each job title. The model was
      partially validated with actual exposure measurements. The exposure estimates
      from the deterministic model were used to construct a job-exposure matrix that
      will enable estimation of cumulative exposures for each cohort member. The
      generic approach described for estimating chronic MRI-related SMF exposure makes
      it universally applicable in other studies investigating health effects of MRI
      related SMF exposure. 

PMID- 24081381
TI  - A unique carbon with a high specific surface area produced by the carbonization
      of agar in the presence of graphene.
AB  - A unique carbon with a high specific surface area was prepared by carbonization
      of a polymer-based precursor, agar, in the presence of graphene. Graphene
      prevents the shrinkage and aggregation of the carbonized particles, resulting in
      extraordinarily large external surface area (~1200 m(2) g(-1)) of the carbon,
      which shows a high rate performance as a supercapacitor electrode. 

PMID- 24081378
TI  - Can BACE1 inhibition mitigate early axonal pathology in neurological diseases?
AB  - beta-Secretase-1 (BACE1) is the rate-limiting enzyme for the genesis of amyloid
      beta (Abeta) peptides, the main constituents of the amyloid plaques in the brains
      of Alzheimer's disease (AD) patients. BACE1 is being evaluated as an anti-Abeta
      target for AD therapy. Recent studies indicate that BACE1 elevation is associated
      with axonal and presynaptic pathology during plaque development. Evidence also
      points to a biological role for BACE1 in axonal outgrowth and synapse formation
      during development. Axonal, including presynaptic, pathology exists in AD as well
      as many other neurological disorders such as Parkinson's disease, epilepsy,
      stroke, and trauma. In this review, we discuss pharmaceutical BACE1 inhibition as
      a therapeutic option for axonal pathogenesis, in addition to amyloid pathology.
      We first introduce the amyloidogenic processing of amyloid-beta protein precursor
      and describe the normal expression pattern of the amyloidogenic proteins in the
      brain, with an emphasis on BACE1. We then address BACE1 elevation relative to
      amyloid plaque development, followed by updating recent understanding of a
      neurotrophic role of BACE1 in axon and synapse development. We further elaborate
      the occurrence of axonal pathology in some other neurological conditions.
      Finally, we propose pharmacological inhibition of excessive BACE1 activity as an
      option to mitigate early axonal pathology occurring in AD and other neurological
      disorders. 

PMID- 24081382
TI  - Monetite and brushite coated magnesium: in vivo and in vitro models for
      degradation analysis.
AB  - The use of magnesium (Mg) as a biodegradable metallic replacement of permanent
      orthopaedic materials is a current topic of interest and investigation. The
      appropriate biocompatibility, elastic modulus and mechanical properties of Mg
      recommend its suitability for bone fracture fixation. However, the degradation
      rates of Mg can be rapid and unpredictable resulting in mass hydrogen production
      and potential loss of mechanical integrity. Thus the application of calcium
      phosphate coatings has been considered as a means of improving the degradation
      properties of Mg. Brushite and monetite are utilized and their degradation
      properties (alongside uncoated Mg controls) are assessed in an in vivo
      subcutaneous environment and the findings compared to their in vitro degradation
      behaviour in immersion tests. The current findings suggest monetite coatings have
      significant degradation protective effects compared to brushite coatings in vivo.
      Furthermore, it is postulated that an in vitro immersion test may be used as a
      tentative predictor of in vivo subcutaneous degradation behavior of calcium
      phosphate coated and uncoated Mg. 

PMID- 24081384
TI  - Cerebral microbleeds in lupus anticoagulant-hypoprothrombinemia syndrome.

PMID- 24081383
TI  - Application of carbon nanotubes layered on silicon wafer for the detection of
      breast cancer marker carbohydrate antigen 15-3 by immuno-polymerase chain
      reaction.
AB  - A highly sensitive detection of breast cancer marker, carbohydrate antigen 15-3
      (CA 15-3) by carbon nanotube (CNT) based immuno-polymerase chain reaction was
      reported. The study was aimed to develop a precise and sensitive method to
      diagnose breast cancer and its recurrence. The hydrofluoric acid (HF) treated
      silicon wafer layered with bundled CNT was used as the substrate. The surface was
      treated with HNO3/H2SO4 to graft carboxyl groups on the tips of CNT.
      Subsequently, polyoxyethylene bis-amine was grafted to conjugate anti human CA 15
      3 antibodies. Water contact angle measurement, scanning electron microscope,
      Fourier transform infrared spectrometer, Raman spectrometer and sodium dodecyl
      sulfate polyacrylamide gel electrophoresis were employed to confirm the surface
      modification. The captured antibodies on the CNT were used to capture the target
      antigen CA 15-3 and the biotinylated secondary antibodies were subsequently bound
      with the target antigen. A bi-functional streptavidin was used to link
      biotinylated DNA to the biotinylated detection antibodies. The biotinylated
      target DNA was amplified by PCR, and then analyzed by agarose gel
      electrophoresis. The lower limit of detection of CA 15-3 by the proposed immuno
      PCR system was 0.001 U/mL, which is extremely sensitive than the other
      bioanalytical techniques.

PMID- 24081385
TI  - Electrical stimulation promotes maturation of cardiomyocytes derived from human
      embryonic stem cells.
AB  - While human embryonic stem cells (hESCs) can differentiate into functional
      cardiomyocytes, their immature phenotypes limit their therapeutic application for
      myocardial regeneration. We sought to determine whether electrical stimulation
      could enhance the differentiation and maturation of hESC-derived cardiomyocytes.
      Cardiac differentiation was induced in a HES3 hESC line via embryoid bodies
      formation treated with a p38 MAP kinase inhibitor. Detailed molecular and
      functional analysis were performed in those hESC-derived cardiomyocytes cultured
      for 4 days in the absence or presence of electrical field stimulation (6.6 V/cm,
      1 Hz, and 2 ms pulses) using an eight-channel C-Pace stimulator (Ion-Optics Co.,
      MA). Upon electrical stimulation, quantitative polymerase chain reaction
      demonstrated significant upregulation of cardiac-specific gene expression
      including HCN1, MLC2V, SCN5A, SERCA, Kv4.3, and GATA4; immunostaining and flow
      cytometry analysis revealed cellular elongation and an increased proportion of
      troponin-T positive cells (6.3 +/- 1.2% vs. 15.8 +/- 2.1%; n = 3, P < 0.01).
      Electrophysiological studies showed an increase in the proportion of ventricular
      like hESC-derived cardiomyocytes (48 vs. 29%, P < 0.05) with lengthening of their
      action potential duration at 90% repolarization (387.7 +/- 35.35; n = 11 vs.
      291.8 +/- 20.82; n = 10, P < 0.05) and 50% repolarization (313.9 +/- 27.94; n =
      11 vs. 234.0 +/- 16.10; n = 10, P < 0.05) after electrical stimulation.
      Nonetheless, the membrane diastolic potentials and action potential upstrokes of
      different hESC-derived cardiomyocyte phenotypes, and the overall beating rate
      remained unchanged (all P > 0.05). Fluorescence confocal imaging revealed that
      electrical stimulation significantly increased both spontaneous and caffeine
      induced calcium flux in the hESC-derived cardiomyocytes (approximately 1.6-fold
      for both cases; P < 0.01). In conclusion, electrical field stimulation increased
      the expression of cardiac-specific genes and the yield of differentiation,
      promoted ventricular-like phenotypes, and improved the calcium handling of hESC
      derived cardiomyocytes.

PMID- 24081386
TI  - Rethinking warfarin for atrial fibrillation.

PMID- 24081387
TI  - Dolutegravir (Tivicay) for HIV.

PMID- 24081388
TI  - Radium - 223 (Xofigo) for prostate cancer.

PMID- 24081389
TI  - Photooxygenation mechanisms in naproxen-amino acid linked systems.
AB  - The photooxygenation of model compounds containing the two enantiomers of
      naproxen (NPX) covalently linked to histidine (His), tryptophan (Trp) and
      tyrosine (Tyr) has been investigated by steady state irradiation, fluorescence
      spectroscopy and laser flash photolysis. The NPX-His systems presented the
      highest oxygen-mediated photoreactivity. Their fluorescence spectra matched that
      of isolated NPX and showed a clear quenching by oxygen, leading to a diminished
      production of the NPX triplet excited state ((3)NPX*-His). Analysis of the NPX
      His and NPX-Trp photolysates by UPLC-MS-MS revealed in both cases the formation
      of two photoproducts, arising from the reaction of singlet oxygen ((1)O2) with
      the amino acid moiety. The most remarkable feature of NPX-Trp systems was a fast
      and stereoselective intramolecular fluorescence quenching, which prevented the
      efficient formation of (3)NPX*-Trp, thus explaining their lower reactivity
      towards photooxygenation. Finally, the NPX-Tyr systems were nearly unreactive and
      exhibited photophysical properties essentially coincident with those of the
      parent NPX. Overall, these results point to a type II photooxygenation mechanism,
      triggered by generation of (1)O2 from the (3)NPX* chromophore. 

PMID- 24081390
TI  - Green tea catechins: a fresh flavor to anticancer therapy.
AB  - Green tea catechins have been extensively studied for their cancer preventive
      effects. Accumulating evidence has shown that green tea catechins, like (-)
      epigallocatechin-3-gallate, have strong anti-oxidant activity and affect several
      signal transduction pathways relevant to cancer development. Here, we review the
      biological properties of green tea catechins and the molecular mechanisms of
      their anticancer effects, including the suppression of cancer cell proliferation,
      induction of apoptosis, and inhibition of tumor metastasis and angiogenesis. We
      summarize the efficacy of a single catechin and the synergetic effects of
      multiple catechins. We also discuss the enhanced anticancer effects of green tea
      catechins when they are combined with anticancer drugs. The information present
      in this review might promote the development of strategy for the co
      administration of green tea catechins with other anticancer drugs to increase the
      potency of currently available anticancer medicine. This new strategy should in
      turn lower the cytotoxicity and cost of anticancer treatment. 

PMID- 24081391
TI  - Surgical procedures and prognostic factors for local recurrence of soft tissue
      sarcomas.
AB  - BACKGROUND: Patients with local recurrence of soft tissue sarcomas are
      predisposed to future recurrences because treatment is challenging and
      complicated by prior therapy. This study investigated clinical outcomes following
      surgical procedures for locally recurrent soft tissue sarcomas and risk factors
      for re-recurrence and metastasis. METHODS: A retrospective analysis was conducted
      with 105 patients (52 males, 53 females) who underwent surgical procedures for
      local recurrence without distant metastasis of soft tissue sarcoma between 1987
      and 2009. Patient follow-up ranged from 1 to 12 years (mean 4.9 years). RESULTS:
      Overall 5- and 10-year survival rates were 83.4 and 67.7%, respectively. Twenty
      one patients (20.0%) had additional local recurrences, and 23 (21.9%) had distant
      metastases. Amputation rate was 10.5% at the time of surgical procedures and
      17.1% at final follow-up. Locations deep within muscles in the upper limb or
      trunk and surgical margins <1 cm wide were risk factors for further local
      recurrence. Locations deep within muscles, tumor sizes >10 cm, high-grade
      malignancy, and local recurrence after radical surgery were risk factors for
      distant metastasis. CONCLUSIONS: Surgical margin and location were independent
      prognostic factors for local control, and a wider margin was especially important
      for recurrent tumors located in the trunk and upper extremity. For high-grade
      sarcomas with local recurrence after radical surgery, new approaches are needed
      to prevent distant metastases.

PMID- 24081392
TI  - Causative factors of fracture nonunion: the proportions of mechanical,
      biological, patient-dependent, and patient-independent factors.
AB  - BACKGROUND: Understanding the causative factors of fracture nonunion leads to
      both prevention and improvements in treatment. The purpose of this study was to
      understand the clinical characteristics and causative factors of nonunion in a
      case series. METHODS: One hundred two consecutive patients with fracture
      nonunions of the extremities who were surgically treated in our hospital over the
      last decade were analyzed. Data were collected by reviewing medical charts.
      Radiographs were reviewed to classify the nonunion by radiographic appearance.
      Causative factors of nonunions were identified for each patient. Factors relating
      to inadequate mechanical stability or reduction and those relating to a decline
      in biological activity were investigated. Mechanical factors included
      inappropriate dynamization, inappropriate reduction, inappropriate surgical
      management, insufficient fixation, and conservative treatment. Surgical technical
      errors were identified through careful review by three experienced trauma
      surgeons. Biological activity factors included comminution and bone loss, open
      fracture, excessive surgical exposure, infection, previous radiation therapy,
      alcohol abuse, diabetes mellitus, smoking, genetic disorders, and metabolic
      disease or endocrine pathology. We also classified the causative factors as
      patient-dependent or patient-independent factors. RESULTS: Of the 102 nonunions,
      47 were oligotrophic, 22 were hypertrophic, 17 were atrophic, 12 were defect
      types, and 4 were comminuted. Twenty-four cases had factors of inadequate
      mechanical stability or reduction, 23 cases had biological factors, and 55 cases
      had both types of factors. Four cases had patient-dependent factors, 40 cases had
      patient-independent factors, and 58 cases had both types of factors. CONCLUSIONS:
      Our results demonstrated that there were a considerable number of nonunions with
      causative factors which can be improved, such as inadequate fracture management.

PMID- 24081393
TI  - [Understand, investigate and diagnose pain in the musculoskeletal system].
AB  - Most patients who attend orthopedic trauma surgery practices present with pain of
      the musculoskeletal system which can significantly affect the quality of life.
      For most patients the reason for the pain is quite obvious and can be easily
      addressed; however, for other patients the mechanism responsible for the pain
      remains unclear. In these patients it is mandatory to have well founded knowledge
      about the origin of the pain, possible pathways of pain sensitization and
      chronification in order to ask the right questions during (pain) anamnesis and to
      perform an adequate clinical functional examination. This is the foundation to
      offer an effective treatment to patients or when necessary to initiate further
      diagnostic investigations in order to avoid pain chronification or to direct
      patients to a multimodal interdisciplinary approach when the pain is already
      chronic. 

PMID- 24081394
TI  - [Endoprosthesis].

PMID- 24081395
TI  - [Legg-Calve-Perthes disease (LCPD). Principles of diagnosis and treatment].
AB  - BACKGROUND: The clinical course of Legg-Calve-Perthes disease (LCPD) is variable.
      Diagnosis, nonsurgical and surgical methods of treatment have evolved over many
      decades, from abduction casts and braces to advanced surgical containment methods
      which are now the mainstay of treatment. METHODS: This article presents a general
      view and a critical evaluation of the literature. RESULTS: The main prognostic
      factors are patient age at the onset of LCPD, the range of motion and the extent
      of the necrotic process according to the classification of Herring and Catterall.
      The main aims of surgical and nonsurgical treatment of LCPD are to prevent
      prearthrotic deformity of the femoral head, relief of symptoms, containment of
      the femoral head and restoration of congruence of the hip joint. CONCLUSIONS:
      Each patient needs to be evaluated individually. Every child must receive an
      adapted treatment and continued follow-up at regular intervals.

PMID- 24081396
TI  - The diagnosis and surgical treatment of pancreatoblastoma in adults: a case
      series and review of the literature.
AB  - INTRODUCTION: Pancreatoblastoma is an extremely rare pancreatic neoplasm in
      adults. The aim of this study is to report our experience with adult
      pancreatoblastoma as well as review the cases reported in the literature in order
      to provide guidelines for the management of patients with this rare neoplasm.
      METHODS: We have encountered three cases of pancreatoblastoma in adults at our
      institution in addition to the 30 cases reported to date in literature. RESULTS:
      The median age of pancreatoblastoma in adults is 37 years (range, 18-78 years);
      men and women are similarly affected (male/female = 16/17). The behavior of
      pancreatoblastoma is clearly that of a malignant neoplasm, with local invasion,
      recurrence, and metastasis. Among the adult reported cases, at diagnosis or
      operation, metastasis and/or local invasion was found in 14 of 31 adult patients
      (46 %) (2 patients had no data) The survival was significantly higher in patients
      with resected tumor (resection only and resection + adjuvant chemo/radiotherapy)
      when compared to unresected patients (palliative chemo/radiotherapy and no
      treatment), (p = 0.008, HR = 0.20). CONCLUSION: When disease is localized, the
      treatment of choice is a complete surgical resection. The role of adjuvant
      chemotherapy or radiotherapy is still unclear based on the very small number of
      patients treated.

PMID- 24081397
TI  - What do we expect from parity?

PMID- 24081399
TI  - Datapoints: Prevalence of QT prolongation among veterans with severe mental
      illness.

PMID- 24081401
TI  - Personal accounts: Mental disorders: pathways to hope . . . ?

PMID- 24081400
TI  - Law & psychiatry: Does the constitution require an insanity defense?
AB  - Idaho is one of four states that have abolished the insanity defense. Hence, John
      Delling, on trial for two murders in Idaho, was unable to plead insanity or to
      argue that he lacked intent to kill, the only available option under Idaho law.
      After being sentenced to life in prison without parole, Delling challenged the
      constitutionality of Idaho's law. The state's supreme court rejected his appeal,
      holding that--despite the long history of the insanity defense and its widespread
      acceptance--there was no constitutional right to an insanity defense. Delling's
      petition to the U.S. Supreme Court was turned away, leaving the constitutional
      status of the insanity defense uncertain.

PMID- 24081402
TI  - National trends in the use of antidepressants between 1997 and 2009 and the role
      of Medicare Part D implementation.
AB  - OBJECTIVES: This study examined national trends in antidepressant use before and
      after implementation of Medicare Part D and compared utilization among
      individuals with different types of insurance. METHODS: The data source was the
      Medical Expenditure Panel Survey Household Component (1997-2009), and logistic
      regression was used for the analysis. RESULTS: The odds of antidepressant use
      among people with depression increased between 1997 and 2009 in each insurance
      group (Medicare: adjusted odds ratio [AOR]=3.30, 95% confidence interval
      [CI]=1.84-5.92; Medicaid: AOR=2.97, CI=2.01-4.40; dually eligible for Medicare
      and Medicaid: AOR=2.24, CI=1.11-4.54; and private coverage: AOR=6.63, CI=5.23
      8.42). The odds of antidepressant use after implementation of Part D increased
      more among Medicare beneficiaries than among Medicaid beneficiaries (AOR=1.35,
      CI=1.05-1.72). CONCLUSIONS: The use of antidepressants among people with
      depression increased in all insurance groups up to 2009; however, the patterns of
      utilization and the degree of increase over time differed by insurance type.

PMID- 24081403
TI  - Characteristics of participants in jail diversion and prison reentry programs:
      implications for forensic ACT.
AB  - OBJECTIVE: More research is needed about forensic assertive community treatment
      (FACT) and challenges that offenders with severe mental illness present to jail
      diversion and prison reentry teams. Jail diversion and prison reentry populations
      may require different interventions and strategies to engage and serve them.
      METHODS: This study used data from a mental health agency in a large urban area
      in Ohio to compare the demographic and clinical characteristics of 212 consumers
      served by jail diversion FACT teams and 192 consumers served by prison reentry
      FACT teams. RESULTS: Findings suggest that jail diversion and prison reentry
      consumers have different demographic and clinical profiles, which may present
      unique challenges to FACT teams. CONCLUSIONS: Population- and gender-specific
      strategies and interventions could be warranted to better serve FACT consumers.
      This study furthers the literature about the needs of justice-involved consumers
      and offers important information for providers of FACT for jail diversion and
      prison reentry.

PMID- 24081404
TI  - Screening for mental illness among persons in Amsterdam police custody.
AB  - OBJECTIVE: Research on the mental health of police detainees is scarce. This
      study aimed to identify the proportion of persons detained by the Police Service
      Amsterdam-Amstelland who screened positive for a serious mental condition.
      METHODS: A survey conducted in 2009 among 264 randomly selected detainees
      assessed demographic characteristics and general medical and mental health and
      included use of the Brief Jail Mental Health Screen (BJMHS) (N=248). RESULTS:
      Almost 40% of survey respondents screened positive on the BJMHS, indicating a
      need for further evaluation. This rate was lower than the rate reported for
      police detainees in Australia but substantially higher than the rates reported
      for persons incarcerated in U.S. jails. CONCLUSIONS: More systematic research is
      needed to examine reasons for reports of different rates of mental illness among
      detainees in different countries.

PMID- 24081405
TI  - How states use Medicaid to fund community-based services to children with autism
      spectrum disorders.
AB  - OBJECTIVE: This study examined the extent to which state Medicaid agencies funded
      16 services for children with autism spectrum disorders: individual therapy,
      physical and occupational therapy, in-home supports, speech therapy, diagnostic
      assessment, behavior modification, family therapy, case management, targeted case
      management, respite, day treatment, social skills training, habilitation
      services, treatment planning, family education and training, and assistive
      communication devices. METHODS: Procedure codes in the Medicaid Analytic eXtract
      (MAX) "other therapies" file were used to identify community-based services
      commonly delivered to children with a diagnosis of a primary autism spectrum
      disorder. RESULTS: Four services are commonly used to address the core deficits
      of these disorders: physical and occupational therapy, speech therapy, behavior
      modification, and social skills training. Only six states funded all four
      services. CONCLUSIONS: States varied considerably in use of Medicaid to reimburse
      these services, indicating that some states may have opportunities to receive
      federal matching funds.

PMID- 24081406
TI  - Community mental health provider modifications to cognitive therapy: implications
      for sustainability.
AB  - OBJECTIVE: This study identified modifications to an evidence-based psychosocial
      treatment (cognitive therapy) within a community mental health system after
      clinicians had received intensive training and consultation. METHODS: A coding
      system, consisting of four types of contextual modifications, 12 types of content
      related modifications, seven levels at which modifications can occur, and a code
      for changes to training or evaluation processes, was applied to data from
      interviews with 27 clinicians who treat adult consumers within a mental health
      system. RESULTS: Nine of 12 content modifications were endorsed, and four
      (tailoring, integration into other therapeutic approaches, loosening structure,
      and drift) accounted for 65% of all modifications identified. Contextual
      modifications were rarely endorsed by clinicians in this sample. Modifications
      typically occurred at the client or clinician level. CONCLUSIONS: Clinicians in
      community mental health settings made several modifications to an evidence-based
      practice (EBP), often in an effort to improve the fit of the intervention to the
      client's needs or to the clinician's therapeutic style. These findings have
      implications for implementation and sustainability of EBPs in community settings,
      client-level outcomes, and training and consultation.

PMID- 24081407
TI  - Screening for metabolic risk among patients with severe mental illness and
      diabetes: a national comparison.
AB  - OBJECTIVE: People with severe mental illness have a higher risk of developing
      cardiovascular disease and die sooner than the general population. This study of
      a national sample of primary care patients in the United Kingdom compared
      screening for cardiometabolic risk factors among patients with severe mental
      illness and diabetes. METHODS: Screening for cardiovascular disease among
      2,488,948 patients with diabetes (2010-2011) and 422,966 patients with severe
      mental illness (2011-2012) at 8,123 primary care practices was compared. RESULTS:
      The percentage of patients who received screening across four parameters (body
      mass index, blood pressure, blood glucose, and cholesterol) in the previous 15
      months was higher among patients with diabetes than among those with severe
      mental illness (97.3% versus 74.7%, p<.001). CONCLUSIONS: The proportion of
      patients in primary care who were given screening for cardiometabolic risk was
      much lower among those with severe mental illness than among those with diabetes.

PMID- 24081408
TI  - 2013 APA Achievement Awards: four exemplary programs.

PMID- 24081409
TI  - Social realities in China today.

PMID- 24081410
TI  - Social realities in China today: in reply.

PMID- 24081411
TI  - Axis V: essential supplement to the DSM-5.

PMID- 24081412
TI  - Axis V: essential supplement to the DSM-5: in reply.

PMID- 24081413
TI  - A personalized patient page.

PMID- 24081414
TI  - Low depression screening rates in U.S. ambulatory care.

PMID- 24081415
TI  - The pedagogy of recovery.

PMID- 24081420
TI  - 2013 APA Silver Award: On-campus VA mental health and social work services for
      student veterans: SFVAMC's veterans outreach program at City College of San
      Francisco.

PMID- 24081421
TI  - 2013 APA Bronze Award: Family-based, integrated care for children and adolescents
      with complex pediatric illness: Hasbro Children's Partial Hospital Program,
      Hasbro Children's Hospital, Rhode Island Hospital, Providence.

PMID- 24081422
TI  - 2013 APA Gold Award: Accessible care for New York City residents with serious
      mental illness and a history of homelessness: Center for Urban Community Services
      Janian Medical Care, New York City.

PMID- 24081423
TI  - 2013 APA Gold Award: Amplifying the voices of individuals who use mental health
      services: a commitment to shared decision making: decision support centers,
      community care behavioral health organization, Pittsburgh, Pennsylvania.

PMID- 24081424
TI  - Combining areal DXA bone mineral density and vertebrae postero-anterior width
      improves the prediction of vertebral strength.
AB  - OBJECTIVE: Areal bone mineral density (aBMD) measured by dual-energy X-ray
      absorptiometry (DXA) is an important determinant of bone strength (BS), despite
      the fact that the correlation between aBMD and BS is relatively weak. Parameters
      that describe BS more accurately are desired. The aim of this study was to
      determine whether the geometrical corrections applied to aBMD would improve its
      ability for BS prediction. We considered new parameters, estimated from a single
      DXA measurement, as well as BMAD (bone mineral apparent density) reported in the
      literature. MATERIALS AND METHODS: In vitro studies were performed with the L3
      vertebrae from 20 cadavers, which were studied with DXA and quantitative computed
      tomography (QCT). A mechanical strength assessment was carried out. Two new
      parameters were introduced: vBMD(min) = aBMD/W(PA)(min) and vBMD(av) =
      aBMD/W(PA)(av) (W PA(min) -minimal vertebral body width in postero-anterior (PA)
      view, W(PA)(av) - average PA vertebral body width). Volumetric BMD measured by
      QCT (vBMD), aBMD, BMAD, vBMD(min), and vBMD(av) were correlated to ultimate load
      and ultimate stress (P(max)) to find the best predictor of vertebrae BS. RESULTS:
      The coefficients of correlation between P(max) and vBMD(min), vBMD(av), as well
      as BMAD, were r = 0.626 (p = 0.005), r = 0.610 (p = 0.006) and r = 0.567 (p =
      0.012), respectively. Coefficients for vBMD and aBMD are r = 0.648 (p = 0.003)
      and r = 0.511 (p = 0.03), respectively. CONCLUSIONS: Our results showed that aBMD
      normalized by vertebrae dimensions describes vertebrae BS better than aBMD alone.
      The considered indices vBMD(av), vBMD(min), and BMAD can be measured in routine
      PA DXA and considerably improve BS variability prediction. vBMD(min) is superior
      compared to vBMD(av) and BMAD.

PMID- 24081425
TI  - Nudging for health: on public policy and designing choice architecture.
AB  - There have been recent policy moves aimed at encouraging individuals to lead
      healthier lives. The Cabinet Office has set up a 'nudge unit' with health as one
      of its priorities and behavioural approaches have started to be integrated into
      health-related domestic policy in a number of areas. Behavioural research has
      shown that that the way the environment is constructed can shape a person's
      choices within it. Thus, it is hoped that, by using insights from such research,
      people can be nudged towards making decisions which are better for their health.
      This article outlines how nudges can be conceived of as part of an expanding
      arsenal of health-affecting regulatory tools being used by the Government and
      addresses some concerns which have been expressed regarding behavioural research
      driven regulation and policy. In particular, it makes the case that, regardless
      of new regulatory and policy strategies, we cannot escape the myriad of
      influences which surround us. As such, we can view our health-affecting decisions
      as already being in some sense shaped and constructed. Further, it argues we may
      in fact have reason to prefer sets of health-affecting options which have been
      intentionally designed by the state, rather than those that stem from other
      sources or result from random processes. Even so, in closing, this article draws
      attention to the largely unanswered questions about how behavioural research
      translates into policy and regulatory initiatives. 

PMID- 24081426
TI  - Demonstrating disease activity in patients with rheumatoid arthritis. Is 18F FDG
      PET a sensitive method?
AB  - AIM: We aimed to investigate the relationship of fluor-18 fluorodeoxyglucose
      positron emission tomography/computed tomography (18F FDG PET/CT) with clinical,
      laboratory parameters and conventional radiographs in patients with rheumatoid
      arthritis (RA). PATIENTS, MATERIAL, METHODS: 25 patients with RA diagnosis were
      evaluated by sociodemographic, clinical [duration of disease (year), the joints
      in which the complaints started, most recent joint involvement]; other parameters
      used in RA-specific clinical assessment [Steinbocker functional staging, disease
      activity score 28 (DAS 28 score), health assessment questionnaire score (HAQ
      score), general RA assessment (patients' and physicians' global assessment),
      patients' assessments of pain and general health condition (visual analog
      scale)], laboratory, radiological [conventional radiology of hand and foot
      joints], positron emission tomography [18F FDG PET visual total score and maximum
      standardized uptake value (SUVmax) total score] parameters. RESULTS: No
      significant correlation was detected between the 18F FDG PET total score and
      SUVmax total score of the patients and clinical, laboratory, and radiological
      parameters (p > 0.05). There was no relationship between the cut-off values
      determined according to the disease activity and 18F FDG PET/SUVmax total values
      (p > 0.05). CONCLUSIONS: In our study, no relationship was found between disease
      activity demonstrated by 18F FDG PET/CT in RA patients and clinical, laboratory,
      and radiological parameters. 18F FDG PET/CT appears to be a more sensitive method
      in demonstrating disease activity compared to other evaluated methods.

PMID- 24081427
TI  - A comparison of the efficacy and tolerability of oxcarbazepine oral suspension
      between infants and children with epilepsy: a retrospective chart review at a
      single medical center in Taiwan.
AB  - BACKGROUND: Few clinical studies have assessed the efficacy and safety of
      oxcarbazepine (OXC) oral suspension in Asian pediatric patients and particularly
      in infants. The aim of this study was to investigate and compare the efficacy,
      tolerability, and side effects of OXC oral suspension in Taiwanese infants and
      children with various types of epilepsy. METHODS: A retrospective review of the
      efficacy, tolerability, and side effects of OXC oral suspension in a tertiary
      medical center in Taiwan was conducted and included children (1-9 years old) and
      infants (<1 year old) diagnosed with epilepsy, which was classified into
      idiopathic partial, symptomatic partial, or multifocal subtypes. The OXC oral
      suspension (Trileptal((r)); Novartis) was given in a gradual dose titration, from
      an initial 7.5 mg/kg/day to 30 mg/kg/day within 1 month in all cases. RESULTS: A
      total of 20 infants and 38 children were identified. There were no statistically
      significant differences between the children and infants in efficacy (75 vs. 82
      %, p = 0.734) and adverse effects (30 vs. 21 %, p = 0.525) after OXC oral
      suspension treatment. The efficacy was significantly correlated with the epilepsy
      subtype (p < 0.01) and the number of combined antiepileptic drugs (AEDs) before
      OXC treatment (p < 0.01) in both groups. The patients with idiopathic and
      symptomatic partial epilepsy responded better to OXC oral suspension than those
      with multifocal epilepsy. CONCLUSIONS: OXC oral suspension is effective and well
      tolerated in both infants and children with partial epilepsy in Taiwan. Treatment
      efficacy was related to epilepsy subtype and number of combined AEDs before OXC
      treatment. Monotherapy had an excellent therapeutic response in partial epilepsy
      but not in multifocal epilepsy.

PMID- 24081428
TI  - Rapid CO release from a Mn(I) carbonyl complex derived from azopyridine upon
      exposure to visible light and its phototoxicity toward malignant cells.
AB  - Two Mn(I) carbonyl complexes namely [MnBr(azpy)(CO)3] and
      [Mn(azpy)(CO)3(PPh3)](ClO4) (azpy = 2-phenylazopyridine) have been synthesized
      and characterized. Both complexes exhibit rapid CO release upon exposure to low
      power visible light. [MnBr(azpy)(CO)3] shows significant phototoxicity toward two
      malignant cell lines HeLa and MDA-MB-231.

PMID- 24081429
TI  - Changes in translational efficiency is a dominant regulatory mechanism in the
      environmental response of bacteria.
AB  - To understand how cell physiological state affects mRNA translation, we used
      Shewanella oneidensis MR-1 grown under steady state conditions at either 20% or
      8.5% O2. Using a combination of quantitative proteomics and RNA-Seq, we generated
      high-confidence data on >1000 mRNA and protein pairs. By using a steady state
      model, we found that differences in protein-mRNA ratios were primarily due to
      differences in the translational efficiency of specific genes. When oxygen levels
      were lowered, 28% of the proteins showed at least a 2-fold change in expression.
      Transcription levels were sp. significantly altered for 26% of the protein
      changes; translational efficiency was significantly altered for 46% and a
      combination of both was responsible for the remaining 28%. Changes in
      translational efficiency were significantly correlated with the codon usage
      pattern of the genes and measurable tRNA pools changed in response to altered O2
      levels. Our results suggest that changes in the translational efficiency of
      proteins, in part due to altered tRNA pools, is a major determinant of regulated
      alterations in protein expression levels in bacteria. 

PMID- 24081430
TI  - Liver transplantation versus supraselective transarterial chemoembolization in
      palliative patients with hepatocellular carcinoma exceeding the Milan Criteria -
      is it time for a more individual approach?
AB  - BACKGROUND: This study evaluated the effect of liver transplantation (LTX) and
      STACE on overall survival in palliative patients with HCC exceeding Milan
      criteria. MATERIAL AND METHODS: At a single center 63 HCC patients exceeding
      Milan criteria were retrospectively analyzed. Forty patients underwent STACE as
      palliative therapy modality and 23 palliative patients were scheduled for LTX.
      The primary endpoint was overall patient survival. Statistical analysis included
      Kaplan-Meier method, log rank, chi squared tests and Cox regression model for the
      identification of prognostic factors. RESULTS: There was no significant
      difference when comparing the 2 groups (LTX vs. no LTX) in terms of Child
      classification, co-morbidities, underlying disease, and sex. Overall survival was
      significantly prolonged after LTX was performed (p=0.012). In the Cox regression
      model, LTX (p=0.021), LTX <3Mo (p=0.047), CHILD stage (p=0.007), AFP (p=0.020),
      and tumor size of largest HCC nodule <40 mm (p=0.028) were independent prognostic
      factors for survival. CONCLUSIONS: Palliative patients beyond Milan have a
      significant survival benefit after they received early liver transplantation in
      comparison with STACE. The current approach to waiting list candidacy based on
      Milan criteria should be modified with a more individualized approach that
      considers age, AFP level, and tumor size.

PMID- 24081432
TI  - Emphysematous gastritis: a rare cause of septic shock.

PMID- 24081431
TI  - Our study 20 years on: a randomized clinical trial of the effect of deliberate
      perioperative increase of oxygen delivery on mortality in high-risk surgical
      patients.
AB  - INTRODUCTION: Goal-directed perioperative therapy (GDT) is now part of a number
      of international perioperative protocols and, to some extent, seems to have come
      of age, but no research takes place in isolation and it is valuable to
      retrospectively look at influential papers to understand the context and
      influences of the time the research was undertaken. METHODS: One of the earliest
      publication of a randomised trial of GDT was a study we published 20 years ago in
      1993, with co-author Professor E. David Bennett. In this article we describe the
      work leading up to our research, and look at the historical context of our study
      and choices we made in designing a protocol. CONCLUSION: With 20 years of
      hindsight we consider the issues that have arisen following our study and place
      this into the whole of the debate around the use of GDT.

PMID- 24081434
TI  - Accuracy of plasma neutrophil gelatinase-associated lipocalin in the early
      diagnosis of contrast-induced acute kidney injury in critical illness: reply to
      Quartin et al.

PMID- 24081433
TI  - Bleeding and risk of death with hydroxyethyl starch in severe sepsis: post hoc
      analyses of a randomized clinical trial.
AB  - PURPOSE: We aimed to characterize the degree and clinical importance of bleeding
      in patients treated with hydroxyethyl starch (HES). METHODS: In post hoc
      analyses, we examined the associations between fluid assignment, hemostatic
      variables, bleeding events, transfusions, and death among 798 patients with
      severe sepsis randomized to fluid resuscitation with HES 130/0.42 versus Ringer's
      acetate. We used Cox regression analysis adjusted for fluid assignment and
      baseline characteristics. RESULTS: Overall, 93 (23 %) patients assigned to HES
      versus 60 (15 %) patients assigned to Ringer's acetate bled in the ICU (relative
      risk (RR) 1.55; 95 % CI 1.16-2.08; P = 0.003). Of these, 38 and 25 (RR 1.52; 95 %
      CI 0.94-2.48; P = 0.09), respectively, had severe bleeding (intracranial or
      concomitant transfusion with three units of red blood cells). Most patients bled
      in the first days after randomization when most trial fluid was given. The
      hazards ratios for occurrence of any bleeding and severe bleeding in patients
      treated with HES versus Ringer's acetate were 1.70 (95 % CI 1.23-2.36; P = 0.001)
      and 1.55 (95 % CI 0.93-2.56; P = 0.09), respectively. The adjusted hazard ratios
      for death among patients with any bleeding and severe bleeding compared to those
      without bleeding were 1.36 (95 % CI 1.04-1.79; P = 0.03) and 1.74 (95 % CI 1.20
      2.53; P = 0.004), respectively. CONCLUSIONS: In post hoc analyses of patient with
      severe sepsis, treatment with HES increased the risk of bleeding which was
      associated with increased risk of death. HES-induced bleeding complications may
      negatively affect outcome in patients with severe sepsis.

PMID- 24081435
TI  - Facial cellulitis secondary to chronic non-invasive ventilation.

PMID- 24081436
TI  - A dangerous percutaneous dilatational tracheostomy.

PMID- 24081437
TI  - Veno-venous ECMO in ARDS after post-traumatic pneumonectomy.

PMID- 24081438
TI  - Molecular dynamics simulation of cross-linked urea-formaldehyde polymers for self
      healing nanocomposites: prediction of mechanical properties and glass transition
      temperature.
AB  - Urea-formaldehyde polymers, which are utilized in the adhesives industry, have
      recently been shown to be suitable materials for synthesizing micro/nanocapsules
      for use in self-healing (nano)composites. In this study, molecular dynamics was
      employed to simulate the process in which urea and formaldehyde are cross-linked
      via methylene and ether cross linkers, and to study the structure and
      mechanical/thermal properties of simulated poly(urea-formaldehyde)s (PUFs). The
      elastic stiffness constants of the simulated materials were calculated using the
      constant-strain (static) method. A temperature cycle was applied to the cross
      linked PUFs, and the glass transition behavior of each material was investigated
      through the mean squared displacement (MSD) and temperature evolution of the
      energy and the specific volume of the polymer. The simulation results confirmed
      that there was considerable improvement in the properties of the poly(UF)
      materials upon cross linking. The radial distribution function was also used to
      study the local structures of the polymers, and this revealed that increasing the
      temperature and cross linking density results in a significant drop in hydrogen
      bonding intensity in the cross-linked PUF systems.

PMID- 24081440
TI  - Reversible pure word deafness.

PMID- 24081439
TI  - Fish oil in recent onset rheumatoid arthritis: a randomised, double-blind
      controlled trial within algorithm-based drug use.
AB  - BACKGROUND: The effects of fish oil (FO) in rheumatoid arthritis (RA) have not
      been examined in the context of contemporary treatment of early RA. This study
      examined the effects of high versus low dose FO in early RA employing a 'treat-to
      target' protocol of combination disease-modifying anti-rheumatic drugs (DMARDs).
      METHODS: Patients with RA <12 months' duration and who were DMARD-naive were
      enrolled and randomised 2:1 to FO at a high dose or low dose (for masking). These
      groups, designated FO and control, were given 5.5 or 0.4 g/day, respectively, of
      the omega-3 fats, eicosapentaenoic acid + docosahexaenoic acid. All patients
      received methotrexate (MTX), sulphasalazine and hydroxychloroquine, and DMARD
      doses were adjusted according to an algorithm taking disease activity and
      toxicity into account. DAS28-erythrocyte sedimentation rate, modified Health
      Assessment Questionnaire (mHAQ) and remission were assessed three monthly. The
      primary outcome measure was failure of triple DMARD therapy. RESULTS: In the FO
      group, failure of triple DMARD therapy was lower (HR=0.28 (95% CI 0.12 to 0.63;
      p=0.002) unadjusted and 0.24 (95% CI 0.10 to 0.54; p=0.0006) following adjustment
      for smoking history, shared epitope and baseline anti-cyclic citrullinated
      peptide. The rate of first American College of Rheumatology (ACR) remission was
      significantly greater in the FO compared with the control group (HRs=2.17 (95% CI
      1.07 to 4.42; p=0.03) unadjusted and 2.09 (95% CI 1.02 to 4.30; p=0.04)
      adjusted). There were no differences between groups in MTX dose, DAS28 or mHAQ
      scores, or adverse events. CONCLUSIONS: FO was associated with benefits
      additional to those achieved by combination 'treat-to-target' DMARDs with similar
      MTX use. These included reduced triple DMARD failure and a higher rate of ACR
      remission.

PMID- 24081441
TI  - Memory, mood, and vitamin D in persons with Parkinson's disease.
AB  - BACKGROUND: Research in recent years has suggested a role of vitamin D in the
      central nervous system. The final converting enzyme and the vitamin D receptor
      are found throughout the human brain. From animal studies vitamin D appears
      important in neurodevelopment, up-regulation of neurotrophic factors,
      stabilization of mitochondrial function, and antioxidation. OBJECTIVE: To examine
      the relationship between serum vitamin D and neuropsychiatric function in persons
      with Parkinson's disease (PD). METHODS: This is an add-on study to a longitudinal
      study following neuropsychiatric function in persons with PD. Baseline
      neuropsychiatric performance and serum 25-hydroxyvitamin D were examined for 286
      participants with PD. Measures of global cognitive function (MMSE, MOCA, Mattis
      Dementia Scale), verbal memory (Hopkins Verbal Learning Test), fluency (animals,
      vegetables, and FAS words), visuospatial function (Benton Line Orientation),
      executive function (Trails Making Test and Digit-Symbol Substitution), PD
      severity (Hoehn & Yahr and Unified Parkinson's Disease Rating Scale) and
      depression (Geriatric Depression Scale (GDS)) were administered. Multivariate
      linear regression assessed the association between vitamin D concentration and
      neuropsychiatric function, in the entire cohort as well as the non-demented and
      demented subsets. RESULTS: Using a multivariate model, higher vitamin D
      concentrations were associated with better performance on numerous
      neuropsychiatric tests in the non-demented subset of the cohort. Significant
      associations were specifically found between vitamin D concentration and verbal
      fluency and verbal memory (t = 4.31, p < 0.001 and t = 3.04, p = 0.0083). Vitamin
      D concentrations also correlated with depression scores (t = -3.08, p = 0.0083)
      in the non-demented subset. CONCLUSIONS: Higher plasma vitamin D is associated
      with better cognition and better mood in this sample of PD patients without
      dementia. Determination of causation will require a vitamin D intervention study.

PMID- 24081442
TI  - Quantitative analysis of the effect of triglyceride alkyl-chain length on the
      partitioning of highly lipophilic compounds to the mesenteric lymph in intestinal
      cells.
AB  - The purpose of this study was to quantitatively clarify the effect of alky-chain
      length of a triglyceride in an emulsion on the partitioning of highly lipophilic
      compounds into the lymph fluid after their oral administration. Highly lipophilic
      anthraquinone derivatives were orally administered in emulsions to rats.
      Emulsions composed of long-, medium-, and short-chain triglycerides (LCT, MCT,
      and SCT emulsions, respectively) were used. The concentrations of the compounds
      in plasma and lymph fluid were periodically determined and their partitioning to
      the lymph was calculated using a mathematical model. Intestinal absorption of all
      compounds was enhanced and the plasma concentrations of the compounds were found
      to be in the following order: LCT emulsion > MCT emulsion > SCT emulsion. The
      amounts of each compound recovered in the lymph were not in agreement with their
      lipophilicity. Quantitative analysis revealed that the partitioning of the
      compounds to the lymph may be determined by the solubility of the compound in the
      triglyceride in the form of an emulsion and the amount of triglyceride
      transferred to the lymph fluid. These results suggest a possibility that the
      amount of a compound absorbed via the lymph route after oral administration can
      be quantitatively controlled by the formulations. 

PMID- 24081444
TI  - Capsule commentary on Faerber et al., content analysis of false and misleading
      claims in television advertising for prescription and nonprescription drugs.

PMID- 24081443
TI  - Quality of care for patients with multiple chronic conditions: the role of
      comorbidity interrelatedness.
AB  - Multimorbidity--the presence of multiple chronic conditions in a patient--has a
      profound impact on health, health care utilization, and associated costs.
      Definitions of multimorbidity in clinical care and research have evolved over
      time, initially focusing on a patient's number of comorbidities and the
      associated magnitude of required care processes, and later recognizing the
      potential influence of comorbidity characteristics on patient care and outcomes.
      In this article, we review the relationship between multimorbidity and quality of
      care, and discuss how this relationship may be mediated by the degree to which
      conditions interact with one another to generate clinical complexity (comorbidity
      interrelatedness). Drawing on established theoretical frameworks from cognitive
      engineering and biomedical informatics, we describe how interactions among
      conditions result in clinical complexity and may affect quality of care. We
      discuss how this comorbidity interrelatedness influences the value of existing
      quality guidelines and performance metrics, and describe opportunities to
      quantify this construct using data widely available through electronic health
      records. Incorporating comorbidity interrelatedness into conceptualizations of
      multimorbidity has the potential to enhance clinical and research efforts that
      aim to improve care for patients with multiple chronic conditions.

PMID- 24081445
TI  - The impact of long-term health goals on sexual risk decisions in impulsive and
      reflective cognitive States.
AB  - In the heat of the moment, people often impulsively take risks. Having
      unprotected sex, for example, can result in sexually transmitted infections. In
      three studies, we investigated a possible explanation for the increased sexual
      risk propensity of people in an impulsive state. In contrast to the intuitively
      appealing notion that they are less influenced by their long-term goals, we
      hypothesized and showed that people in both impulsive and reflective states make
      less risky sexual decisions when health goals are important. We further showed
      that, when sexual health goals are important, people in a reflective state make
      riskier sexual decisions as temptations become stronger, while decisions of
      people in an impulsive state were not influenced by temptation strength. This
      supports the counterintuitive prediction that people in an impulsive state are
      better able to cope with strong temptations than people in a reflective state. 

PMID- 24081446
TI  - Nuclear medicine training and practice in Spain.

PMID- 24081447
TI  - Nuclear medicine training and practice in Germany.

PMID- 24081448
TI  - Prognostic significance of preoperative metabolic tumour volume and total lesion
      glycolysis measured by (18)F-FDG PET/CT in squamous cell carcinoma of the oral
      cavity.
AB  - PURPOSE: Metabolic tumour volume (MTV) and total lesion glycolysis (TLG) from
      (18)F-FDG PET/CT are emerging prognostic biomarkers in human solid cancers; yet
      few studies have investigated their clinical and prognostic significance in oral
      cavity squamous cell carcinoma (OSCC). The present retrospective study evaluated
      the utility of pretreatment MTV and TLG measured by (18)F-FDG PET/CT to predict
      survival and occult metastasis (OM) in OSCC. METHODS: Of 162 patients with OSCC
      evaluated preoperatively by (18)F-FDG PET/CT, 105 who underwent definitive
      surgery with or without adjuvant therapy were eligible. Maximum standardized
      uptake value (SUVmax), MTV and TLG were measured. For calculation of MTV, 3-D
      regions of interest were drawn and a SUV threshold of 2.5 was used for defining
      regions. Univariate and multivariate analyses identified clinicopathological and
      imaging variables associated with OM, disease-free survival (DFS) and overall
      survival (OS). RESULTS: The median (range) SUVmax, MTV and TLG were 7.3 (0.7
      41.9), 4.5 ml (0.7-115.1 ml) and 18.3 g (2.4-224.1 g), respectively. Of 53
      patients with clinically negative lymph nodes, OM was detected in 19 (36%). By
      univariate and multivariate analyses, MTV (P = 0.018) and TLG (P = 0.011) were
      both independent predictive factors for OM, although they were not independent of
      each other. The 4-year DFS and OS rates were 53.0% and 62.0%, respectively.
      Univariate and multivariate analyses revealed that MTV (P = 0.001) and TLG (P =
      0.006), with different cut-off levels, were both independent predictive factors
      for DFS, although they were not independent of each other, and MTV (P = 0.001),
      TLG (P = 0.002) and the involved resection margin (P = 0.007) were independent
      predictive factors for OS. CONCLUSION: Pretreatment MTV and TLG may be useful in
      stratifying the likelihood of survival and predicting OM in OSCC.

PMID- 24081449
TI  - Isolated cerebellar metastasis from prostate adenocarcinoma diagnosed by 18F
      fluorocholine PET/CT: a rare but not impossible complication.

PMID- 24081450
TI  - THIK-1 (K2P13.1) is a small-conductance background K(+) channel in rat trigeminal
      ganglion neurons.
AB  - The goal of this study was to determine the molecular identity of a small
      conductance (~5-pS) background K(+) channel expressed in trigeminal ganglion (TG)
      neurons. We tested the hypothesis that the 5-pS channel is a K2P channel by
      comparing the pharmacological and single-channel properties of THIK-1 expressed
      in HEK293 cells. As reported earlier, whole-cell THIK-1 current was inhibited by
      halothane and activated by arachidonic acid. Among 25 additional modulators
      tested, bupivacaine (100 MUM), quinidine (50 MUM) and Ba(2+) (3 mM) and cold (10 
      degrees C) were most effective inhibitors of THIK-1 current (>50 % inhibition).
      In cell-attached patches with high KCl in the pipette and bath solutions, THIK-1
      produced a small-conductance (~5 pS) channel with a weak inwardly rectifying
      current-voltage relationship. Halothane, bupivacaine and cold inhibited the
      single-channel activities of both THIK-1 and the 5-pS channel in TG neurons,
      whereas arachidonic acid augmented them. THIK-1 expressed in HEK293 cells and the
      5-pS channels in TG neurons were insensitive to hypoxia. Reverse transcriptase
      PCR, Western blot and immunocytochemical analyses suggested that THIK-1 mRNA and
      protein were expressed in TG neurons. These results show that THIK-1 is
      functionally expressed in TG neurons and contributes to the background K(+)
      conductance.

PMID- 24081451
TI  - Zebrafish and mouse TASK-2 K(+) channels are inhibited by increased CO2 and
      intracellular acidification.
AB  - TASK-2 is a K2P K(+) channel considered as a candidate to mediate CO2 sensing in
      central chemosensory neurons in mouse. Neuroepithelial cells in zebrafish gills
      sense CO2 levels through an unidentified K2P K(+) channel. We have now obtained
      zfTASK-2 from zebrafish gill tissue that is 49 % identical to mTASK-2. Like its
      mouse equivalent, it is gated both by extra- and intracellular pH being activated
      by alkalinization and inhibited by acidification. The pHi dependence of zfTASK-2
      is similar to that of mTASK-2, with pK 1/2 values of 7.9 and 8.0, respectively,
      but pHo dependence occurs with a pK 1/2 of 8.8 (8.0 for mTASK-2) in line with the
      relatively alkaline plasma pH found in fish. Increasing CO2 led to a rapid,
      concentration-dependent (IC50 ~1.5 % CO2) inhibition of mouse and zfTASK-2 that
      could be resolved into an inhibition by intracellular acidification and a CO2
      effect independent of pHi change. Indeed a CO2 effect persisted despite using
      strongly buffered intracellular solutions abolishing any change in pHi, was
      present in TASK-2-K245A mutant insensitive to pHi, and also under carbonic
      anhydrase inhibition. The mechanism by which TASK-2 senses CO2 is unknown but
      requires the presence of the 245-273 stretch of amino acids in the C terminus
      that comprises numerous basic amino acids and is important in TASK-2 G protein
      subunit binding and regulation of the channel. The described CO2 effect might be
      of importance in the eventual roles played by TASK-2 in chemoreception in mouse
      and zebrafish.

PMID- 24081452
TI  - Type III-B rotaxane dendrimers.
AB  - Type III-B first generation [3]rotaxane and second generation [4]rotaxane
      dendrimers have been synthesized via (1) a modified copper-catalyzed alkyne-azide
      cycloaddition (CuAAC), (2) Glaser-Hay's acetylenic oxidative homo-coupling, and
      (3) amide formation. The dendron does not reveal obvious cytotoxicities in L929
      fibroblast cells. The rotaxane dendrimers can capture ammonia and are switchable
      both in solution and on surfaces. 

PMID- 24081455
TI  - The comparative biomechanics of the reinforced interdental crossover and the
      Stout loop composite splints for mandibular fracture repair in dogs.
AB  - OBJECTIVES: To describe a new technique, the reinforced interdental crossover
      composite splint (RIC), for transverse mandibular fracture repair in dogs. This
      technique was compared biomechanically with the established reinforced
      interdental Stout loop composite splint (RIS) technique. METHODS: Six pairs of
      mandibles from young adult small breed dogs were used for the study. Osteotomies
      were created in a standardized fashion and fixed with either RIC or RIS. All
      composite splint constructs were tested biomechanically with a cantilever bending
      force, using a single column testing machine at a rate of 2 mm/min. The time of
      application, amount of composite used, ultimate force, stiffness, total
      displacement, and total energy absorbed during displacement of the rostral
      mandibular segment were calculated and compared between the two groups. RESULTS:
      No significant difference was found when comparing the time of application of the
      RIC and the RIS techniques. All implants failed by either composite resin
      fracture over the region of the osteotomy or by fracture between the first and
      second molar followed by detachment of the resin from the lingual enamel surface
      of the first molar. Differences between the RIC and RIS in force (80.5 N +/- 40.3
      and 51.8 N +/- 27.4. respectively) and stiffness (16.2 N/mm +/- 4.4 and 10.1 N/mm
      +/- 4.1 respectively) were significant (p = 0.03). However differences between
      the two techniques in displacement and total energy absorbed were not
      significant. CLINICAL SIGNIFICANCE: In experimentally fractured mandibles of
      young adult dogs there is evidence that RIC is biomechanically similar to RIS.

PMID- 24081453
TI  - Patient preferences for the treatment of type 2 diabetes: a scoping review.
AB  - BACKGROUND: As more studies report on patient preferences, techniques are needed
      to identify, assess and, eventually, synthesize results from a diverse set of
      methodologies. Data on patient preferences are valuable to decision makers in a
      variety of ways. Preferences for outcomes can be used to inform decision and cost
      effectiveness models, while preferences for treatments can inform patient
      centered outcomes research (PCOR) and patient-centered care. OBJECTIVES: This
      project sought to identify and assess the literature reporting on the treatment
      preferences of adult patients with type 2 diabetes. In addition to cataloging the
      preference elicitation methods used, we developed and assessed a novel quality
      assessment checklist for preference-based studies. DATA SOURCES: PubMed, EMBASE,
      CINAHL, and EconLit databases were searched to identify studies examining patient
      preferences for medications for type 2 diabetes studies published since inception
      of each database. STUDY ELIGIBILITY CRITERIA, PARTICIPANTS, AND INTERVENTIONS:
      The review protocol specified inclusion of studies reporting diabetes-treatment
      preferences among adults with type 2 diabetes, using a range of preference
      measurement methods. Studies were excluded if participants were not patients with
      type 2 diabetes and if treatments were not pharmacological therapies targeting
      glycemic control, or if no primary preference information was collected. Two
      investigators independently reviewed titles, abstracts, and articles sequentially
      to select studies for data abstraction based on the inclusion and exclusion
      criteria. Disagreements were resolved by consensus. STUDY APPRAISAL AND SYNTHESIS
      METHODS: Data on study country, year, number of respondents, preference
      elicitation method, number of attributes, subgroup analyses, and funding source
      were abstracted into standardized tables. A novel checklist (PREFS) was used to
      assess the data quality and validity across different types of preference studies
      by assessing the following: purpose of the study; respondent sampling;
      explanation of preference assessment methods; findings reported for total sample;
      and significance testing. Each item was scored, and an aggregate score was then
      calculated (ranging from 0 to 5). RESULTS: Of the 2,100 unique citations, 61 met
      the inclusion criteria. The studies used conjoint analysis (n = 10), time trade
      off (n = 6), standard gamble (n = 2), contingent valuation (n = 1), other stated
      preference methods (n = 39), and revealed preferences (n = 5). Sample sizes
      ranged from 27 to 14,033, with an average of 562 respondents, and two-thirds
      included a subgroup analysis. Most studies were conducted in one country,
      predominantly the USA (n = 27), UK (n = 14), Canada (n = 10), and Germany (n =
      7), while 14 were conducted in multiple (2-18) countries across two or more
      countries. There was an increase in the annual rate of studies published over
      time from the time of the first publication in 1985 (p = < 0.01). Most (n = 52)
      studies were funded by pharmaceutical or device companies, with government,
      academic, association, and hospital sources also funding studies. One study met
      all five of the PREFS criteria and 12 met four; yet four studies met none of the
      criteria. The average was 27. LIMITATIONS: Currently, preferences reviews are
      limited by the mixed quality in the reporting of studies, the publication bias
      inherent in the literature, a lack of guidelines to conduct various methods, and
      the difficulty of synthesizing results from different studies. Our study is also
      limited by its focus on English language articles. CONCLUSIONS AND IMPLICATIONS
      OF KEY FINDINGS: This study provides the first systematic evaluation of the
      methods used in the broad existing body of research into patient preferences for
      type 2 diabetes medications and can serve as a primary source of information for
      decision makers. Future work is necessary to assess the utility of the results of
      reviews of preference information and to develop best-practice guidelines for the
      reporting of, and methods of conducting, preference studies and systematic
      reviews of such studies. REGISTRATION: This systematic review was registered with
      PROSPERO (registration number CRD42012002285).

PMID- 24081454
TI  - The role of companionship, esteem, and informational support in explaining
      physical activity among young women in an online social network intervention.
AB  - The primary objective of the current study was to examine the relationship
      between social support and physical activity within the theory of planned
      behavior (TPB) theoretical framework. This study used data from the Internet
      Support for Healthy Associations Promoting Exercise randomized controlled trial.
      A total of 134 female undergraduate students participated in the study, which
      included baseline and post measures of perceived social support for physical
      activity (esteem, informational, and companionship), TPB variables related to
      physical activity (perceived behavioral control, intention, and attitude), and
      physical activity behavior. Path analysis revealed a significant indirect
      relationship between change in companionship support and physical activity
      mediated by change in intention (.13, p < .01) and a significant direct
      relationship between change in esteem support and change in physical activity
      (.26, p = .03). The model explained 27% of the variance in physical activity and
      59% of the variance in intention. Overall, change in social support exerted a
      small to medium amount of influence on change in physical activity in this
      modified TPB model when controlling for traditional model constructs. Encouraging
      companionship and esteem support should be considered as a strategy for
      increasing physical activity in this population.

PMID- 24081457
TI  - The value of progesterone receptor expression in predicting the Recurrence Score
      for hormone-receptor positive invasive breast cancer patients.
AB  - BACKGROUND: OncotypeDX((r)) (ODX) is a well-validated assay for breast cancer
      treatment planning. We explored whether the conventional pathological factors
      could pick up high risk patients without the help of the ODX. METHODS: The ODX
      was performed on 139 hormone receptor-positive invasive breast cancers in a
      single Japanese institution. The recurrence risk was compared between the ODX and
      the St. Gallen Consensuses. The correlations were analyzed between the Recurrence
      Score (RS) measured by ODX and the pathological factors. In addition, we
      performed a follow-up survey and examined the association of the RS with the
      confirmed recurrence or death. RESULTS: The ODX classified 68 (49 %) as low RS,
      52 (37 %) as intermediate RS, and 19 (14 %) as high RS cases. Correlations were
      noted between RS and progesterone receptor (PR) (r = -0.53), Ki-67 (r = 0.42),
      and nuclear grade (NG) (r = 0.41). None had a high RS with PR(3+) or NG1. Only
      one high RS patient had a Ki-67 (<20 %). The combinations of high RS with
      PR(0)/Ki-67 (>=20 %) and PR(1+)/Ki-67 (>=20 %) were 70 and 58 %, respectively.
      The combinations with high RS and PR(0)/NG3, PR(0)/NG2, and PR(1+)/NG3 were 83,
      75, and 75 %, respectively. The median follow-up was 39.1 months (range 24.0
      67.8). There were one low RS (1 %), four intermediate RS (8 %), and three high RS
      patients (16 %) who developed local or distant recurrence. CONCLUSION: Hormone
      receptor-positive invasive breast cancers are stratified with the combinations of
      PR/Ki-67 or PR/NG. Some of the high recurrence risk cases might be identified
      without the ODX.

PMID- 24081456
TI  - Development and validation of pedigree classification criteria for frontotemporal
      lobar degeneration.
AB  - IMPORTANCE: A significant portion of frontotemporal lobar degeneration (FTLD) is
      due to inherited gene mutations, and we are unaware of a large sequential series
      that includes a recently discovered inherited cause of FTLD. There is also great
      need to develop clinical tools and approaches that will assist clinicians in the
      identification and counseling of patients with FTLD and their families regarding
      the likelihood of an identifiable genetic cause. OBJECTIVES: To ascertain the
      frequency of inherited FTLD and develop validated pedigree classification
      criteria for FTLD that provide a standardized means to evaluate pedigree
      information and insight into the likelihood of mutation-positive genetic test
      results for C9orf72, MAPT, and GRN. DESIGN: Information about pedigrees and DNA
      was collected from 306 serially assessed patients with a clinical diagnosis of
      FTLD. This information included gene test results for C9orf72, MAPT, and GRN.
      Pedigree classification criteria were developed based on a literature review of
      FTLD genetics and pedigree tools and then refined by reviewing mutation-positive
      and -negative pedigrees to determine differentiating characteristics. SETTING:
      Academic medical center. PARTICIPANTS: Patients with FTLD. MAIN OUTCOMES AND
      MEASURES: Familial risk. RESULTS: The rate of C9orf72, MAPT, or GRN mutation
      positive FTLD in this series was 15.4%. Categories designating the risk level for
      hereditary cause were termed high, medium, low, apparent sporadic, and unknown
      significance. Thirty-nine pedigrees (12.7%) met criteria for high, 31 (10.1%) for
      medium, 46 (15.0%) for low, 91 (29.7%) for apparent sporadic, and 99 (32.4%) for
      unknown significance. The mutation-detection rates were as follows: high, 64.1%;
      medium, 29%; low, 10.9%; apparent sporadic, 1.1%; and unknown significance, 7.1%.
      Mutation-detection rates differed significantly between the high and other
      categories. CONCLUSIONS AND RELEVANCE: Mutation rates are high in FTLD spectrum
      disorders, and the proposed criteria provide a validated standard for the
      classification of FTLD pedigrees. The combination of pedigree criteria and
      mutation-detection rates has important implications for genetic counseling and
      testing in clinical settings.

PMID- 24081458
TI  - Design, fabrication and testing of a novel vascular coupling device.
AB  - In this work, an innovative vascular coupling device (VCD) is created to realize
      quick and reliable vessel anastomosis. Vessel anastomosis is common and often
      necessary during trauma, replantation and free tissue transfer surgeries. The
      current method of vessel anastomosis is traditional hand suturing. This technique
      is time consuming (20-30 min), difficult, and requires complex instruments.
      Additionally, it requires very skilled surgeons to efficiently perform the
      operation. To improve the reliability and reduce the amount of time required to
      connect two vessels, while providing an intima-to-intima anastomosis with no
      foreign material in contact with the blood flow, as occurs with sutures, a series
      of VCDs ranging from 1.5 mm to 7 mm inner diameter are designed and fabricated
      from polytetrafluoroethylene (PTFE) using laser cutting. A set of installation
      tools are also designed and fabricated to facilitate the VCD application. A
      series of experiments to test the VCD functionality are performed using both
      latex tubes and arteries. The results showed that the anastomosis process using
      VCDs and the installation tools can be completed in 5 min. The coupled VCDs can
      withstand 20 N tensile force, which is much higher than normal physiology
      conditions. There is no leakage or significant effects of the VCDs on the flow. A
      Micro-CT scan and histology images of cadaver arteries coupled with VCDs
      demonstrated that the VCD keeps the vessels open and does not constrict blood
      flow, suggesting that the VCD could be used in more advanced testing.

PMID- 24081460
TI  - European Hernia Society classification of parastomal hernias.
AB  - PURPOSE: A classification of parastomal hernias (PH) is needed to compare
      different populations described in various trials and cohort studies, complete
      the previous inguinal and ventral hernia classifications of the European Hernia
      Society (EHS) and will be integrated into the EuraHS database (European Registry
      of Abdominal Wall Hernias). METHODS: Several members of the EHS board and invited
      experts gathered for 2 days to discuss the development of an EHS classification
      of PH. The discussions were based on a literature review and critical appraisal
      of existing classifications. RESULTS: The classification proposal is based on the
      PH defect size (small is <=5 cm) and the presence of a concomitant incisional
      hernia (cIH). Four types were defined: Type I, small PH without cIH; Type II,
      small PH with cIH; Type III, large PH without cIH; and Type IV, large PH with
      cIH. In addition, the classification grid includes details about whether the
      hernia recurs after a previous PH repair or whether it is a primary PH. Clinical
      validation is needed in the future to assess if the classification allows us to
      differentiate the treatment strategy and if the classification impacts outcome in
      these different subgroups. CONCLUSION: A classification of PH divided into
      subgroups according to size and cIH was formulated with the aim of improving the
      ability to compare different studies and their results.

PMID- 24081463
TI  - Identification of pharmaceutical impurities in formulated dosage forms.
AB  - Structure elucidation of pharmaceutical impurities is an important part of the
      drug product development process. Impurities can have unwanted pharmacological or
      toxicological effects that seriously impact product quality and patient safety.
      This review focuses on current analytical strategies for chemical and structural
      identification of pharmaceutical impurities. Potential sources and mechanisms of
      impurity formation are discussed for both drug substance and drug product
      applications. The utility of liquid chromatography-mass spectrometry (LC/MS) for
      providing structure-rich information is highlighted throughout this review. Other
      hyphenated analytical techniques including LC/nuclear magnetic resonance, gas
      chromatography/MS, and size-exclusion chromatography/chemiluminescent nitrogen
      detectors are also discussed, as LC/MS alone sometimes cannot reveal or confirm
      the final structures as required during dosage form development.

PMID- 24081462
TI  - Ultraviolet spectroscopy as a tool in therapeutic protein development.
AB  - Ubiquitous ultraviolet absorption spectroscopy, despite the availability of more
      sophisticated techniques, remains an indispensable tool that can give an initial
      insight into the concentration and aggregation state of protein samples. The high
      degree of reproducibility afforded by diode-array spectrophotometers, combined
      with their powerful vendor-supplied algorithms, presents an opportunity for
      improving the accuracy and throughput for their use in pharmaceutical
      development. In this review, factors important to optimal utilization of the
      technique, as applied to the development of monoclonal antibodies, are discussed,
      and specific methodologies are described. In particular, techniques to probe the
      intrinsic structural properties of proteins, and their behavior under a wide
      variety of conditions, through the application of second-derivative spectroscopy
      combined with advanced computational treatments are presented. The information
      contained in this review is specifically directed to practitioners of the
      technique in contemporary research and development settings.

PMID- 24081464
TI  - Polymorphism and solvatomorphism 2009.
AB  - Research papers and issued patents involving polymorphism (i.e., crystal systems
      for which a substance can exist in structures characterized by different unit
      cells, but in which each of the forms has exactly the same elemental composition)
      and solvatomorphism (i.e., systems in which the crystal structures of the
      substance are defined by different unit cells, but wherein these unit cells
      differ in their elemental composition through the inclusion of one or more
      molecules of solvent) have been summarized in an annual review. The works cited
      in this review were published during 2009, and were sourced from the major
      physical, crystallographic, and pharmaceutical journals. The review is divided
      into sections that cover articles of general interest, computational and
      theoretical studies, preparative and isolation methods, structural
      characterization, properties of polymorphic and solvatomorphic systems, studies
      of phase transformations, effects associated with secondary processing, and US
      patents issued during 2009.

PMID- 24081459
TI  - Interdisciplinary European guidelines on metabolic and bariatric surgery.
AB  - In 2012, an expert panel composed of presidents of each of the societies, the
      European Chapter of the International Federation for the Surgery of Obesity (IFSO
      EC), and of the European Association for the Study of Obesity (EASO), as well as
      of the chair of EASO Obesity Management Task Force (EASO OMTF) and other key
      representatives from IFSO-EC and EASO, devoted the joint Medico-Surgical Workshop
      of both institutions to the topic of metabolic surgery in advance of the 2013
      European Congress on Obesity held in Liverpool. This meeting was prompted by the
      extraordinary advancement made in the field of metabolic and bariatric surgery
      during the past decade. It was agreed to revise and update the 2008
      Interdisciplinary European Guidelines on Surgery of Severe Obesity produced by
      focusing in particular on the evidence gathered in relation to the effects on
      diabetes and the changes in the recommendations of patient eligibility criteria.
      The expert panel allowed the coverage of key disciplines in the comprehensive
      management of obesity and obesity-associated diseases, aimed specifically at
      updating the clinical guidelines to reflect current knowledge, expertise and
      evidence-based data on metabolic and bariatric surgery.

PMID- 24081465
TI  - Ensuring global access to quality medicines: role of the US Pharmacopeia.
AB  - In the 5-year cycle that characterizes a continuous improvement of the US
      Pharmacopeial (USP) Convention, the Council of the Convention's Section on Global
      Public Health worked with USP's staff to assess USP's international contributions
      to date and to consider opportunities for expanding activities that help to
      ensure good healthcare around the globe.1 This article reviews USP's process and
      product standards that are used worldwide to ensure the quality of medicines and
      dietary supplements and to help mitigate the burden of counterfeit and
      substandard ingredients and products. The article also reviews USP's
      international programs during the past 5-year cycle, along with continuing and
      planned international activities.

PMID- 24081466
TI  - Predicting the crystallization propensity of carboxylic acid buffers in frozen
      systems--relevance to freeze-drying.
AB  - Selective crystallization of buffer components in frozen solutions is known to
      cause pronounced pH shifts. Our objective was to study the crystallization
      behavior and the consequent pH shift in frozen aqueous carboxylic acid buffers.
      Aqueous carboxylic acid buffers were cooled to -25 degrees C and the pH of the
      solution was measured as a function of temperature. The thermal behavior of
      solutions during freezing and thawing was investigated by differential scanning
      calorimetry. The crystallized phases in frozen solution were identified by X-ray
      diffractometry. The malate buffer system was robust with no evidence of buffer
      component crystallization and hence negligible pH shift. In the citrate and
      tartarate systems, at initial pH <pKa2 , only the most acidic buffer component
      (neutral form) crystallized on cooling, causing an increase in the freeze
      concentrate pH. Carboxylic acid buffers were rank ordered based on their
      propensity to crystallize in frozen solutions. From the aqueous solubility values
      of these carboxylic acids, which have been reported over a range of temperatures,
      it was also possible to estimate the degree of supersaturation at the subambient
      temperature of interest. This enabled us to predict their crystallization
      propensity in frozen systems. The experimental and the predicted rank orderings
      were in excellent agreement.

PMID- 24081467
TI  - Effect of freezing rate and dendritic ice formation on concentration profiles of
      proteins frozen in cylindrical vessels.
AB  - The process of freezing protein solutions can perturb the conformation of the
      protein and potentially lead to aggregate formation during long-term storage in
      the frozen state. Radial macroscopic freeze concentration and temperature
      profiles for bovine serum albumin (BSA) solutions in small cylindrical stainless
      steel vessels were determined for various freezing rates. The measured
      concentrations of both BSA and immunoglobulin G2, as well as trehalose in sampled
      ice sections, increased by up to twofold to threefold toward the bottom and
      radial center for slow freezing rates produced in stagnant air freezers. The
      concentration and temperature profiles result in density gradients that transport
      solutes by convective flow. For faster external cooling by either forced
      convection of air or a liquid coolant, the increased freezing rate raised the ice
      front velocity resulting in enhanced dendritic ice growth. The ice trapped the
      solutes more effectively before they were removed from the ice front by diffusion
      and convection, resulting in more uniform solute concentration profiles. The
      dynamic temperature profiles from multiple radial thermocouples were consistent
      with the independently measured freeze concentration profiles. The ability to
      control the protein concentration profile in the frozen state offers the
      potential to improve stability of protein in long-term frozen storage.

PMID- 24081468
TI  - Screening of monoclonal antibody formulations based on high-throughput
      thermostability and viscosity measurements: design of experiment and statistical
      analysis.
AB  - The purpose of this study was to demonstrate the utility of combining a design of
      experiment (DOE) approach with high-throughput formulation screening to identify
      the main factors affecting protein thermostability and solution viscosity. The
      optimization of buffer compositions was guided by statistical analysis of the
      data to obtain the targeted combination of low viscosity and high
      thermostability. Different monoclonal antibody (mAb) formulation variables were
      evaluated in the study to achieve optimization of two parameters: (i)
      thermostability characterized by temperature of hydrophobic exposure and (ii)
      viscosity. High-throughput measurements were employed to characterize both
      parameters. The significance of each factor and the two-way interactions between
      them was studied by multivariable regression analysis. An experimental design was
      used to estimate the significance of all factors, including interaction effects.
      The range of optimal buffer compositions that maximized thermostability and
      minimized viscosity of a mAb formulation was determined. The described high
      throughput methods are well suited for characterization of multiple protein
      formulation compositions with minimized resources such as time and material. The
      DOE approach can be successfully applied to the screening of mAb formulations
      early in the development lifecycle.

PMID- 24081469
TI  - The relative rate of immunoglobulin gamma 1 fragmentation.
AB  - The physicochemical stability of protein therapeutics is of significant
      pharmaceutical interest. Immunoglobulin gamma (IgG) hinge region fragmentation
      has recently garnered attention as an important degradation route of therapeutic
      monoclonal antibodies. In this work, the rates and relative amount of fragment
      species are compared for five different IgGs (IgG1-5) with widely varying
      solution properties. Native size-exclusion chromatography (SEC), sodium dodecyl
      sulfate (SDS)-based SEC, and capillary electrophoresis-SDS were used to
      characterize IgG1 fragmentation after storage at 30 degrees C, 40 degrees C, and
      50 degrees C. Two-dimensional correlation analysis of the chromatograms as a
      function of time was used to illustrate the relative rates of cleavage.
      Interestingly, the relative rate of Fab cleavage was greater than that of other
      species. An average apparent energy of activation for IgG1 fragmentation was also
      measured for all five molecules. This work suggests that IgG1 fragmentation is
      primarily hinge sequence dependent and other IgG1 molecules should behave
      similarly within the limits of the solution conditions used.

PMID- 24081470
TI  - The biological characteristics and pharmacodynamics of a mycophenolate mofetil
      nanosuspension ophthalmic delivery system in rabbits.
AB  - The purpose of this study was to investigate corneal mucoadhesion,
      pharmacokinetics in lacrimal fluid and aqueous humor, the immune suppression
      induced by corneal transplantation of mycophenolate mofetil (MMF) nanosuspensions
      (NS), and the use of a chitosan-modified MMF nanosuspension (C-NS) as an
      ophthalmic delivery system. The results indicated that NS had a higher drug
      concentration in corneal muscoadhesive samples, lacrimal fluid and aqueous humor
      samples than the MMF ophthalmic suspension. In addition, C-NS had a much higher
      concentration than the NS. The mean survival time of cornea in corneal allografts
      was extended remarkably in the NS and C-NS trial groups. The results confirm that
      the C-NS and NS markedly increase corneal mucoadhesion and drug absorption,
      prolong the survival time of high-risk allografts, and significantly inhibit
      corneal immune rejection in a rabbit model of penetrating keratoplasty. In this
      model, C-NS was more effective than NS.

PMID- 24081471
TI  - Unusual effect of water vapor pressure on dehydration of dibasic calcium
      phosphate dihydrate.
AB  - Dibasic calcium phosphate occurs as an anhydrate (DCPA; CaHPO4) and as a
      dihydrate (DCPD; CaHPO4*2H2O). Our objective was to investigate the unusual
      behavior of these phases. Dibasic calcium phosphate dihydrate was dehydrated in a
      (i) differential scanning calorimeter (DSC) in different pan configurations; (ii)
      variable-temperature X-ray diffractometer (XRD) at atmospheric and under reduced
      pressure, and in sealed capillaries; and (iii) water vapor sorption analyzer at
      varying temperature and humidity conditions. Dehydration was complete by 210
      degrees C in an open DSC pan and under atmospheric pressure in the XRD. Unlike
      "conventional" hydrates, the dehydration of DCPD was facilitated in the presence
      of water vapor. Variable-temperature XRD in a sealed capillary and DSC in a
      hermetic pan with pinhole caused complete dehydration by 100 degrees C and 140
      degrees C, respectively. Under reduced pressure, conversion to the anhydrate was
      incomplete even at 300 degrees C. The increase in dehydration rate with increase
      in water vapor pressure has been explained by the Smith-Topley effect. Under
      "dry" conditions, a coating of poorly crystalline product is believed to form on
      the surface of particles and act as a barrier to further dehydration. However, in
      the presence of water vapor, recrystallization occurs, creating cracks and
      channels and facilitating continued dehydration.

PMID- 24081472
TI  - Influence of chitosan glutamate on the in vivo intranasal absorption of
      rokitamycin from microspheres.
AB  - Intranasal delivery is an alternative method to target therapeutics to the
      central nervous system. In the present study, chitosan glutamate (CG)-based
      mucoadhesive microspheres containing rokitamycin (RK) were prepared by spray
      drying and in vitro characterization. Moreover, the influence of CG on RK
      absorption in bloodstream and cerebrospinal fluid (CSF) was evaluated after nasal
      administration to rats. The in vivo results were compared with those obtained
      after nasal administration of chitosan (CH)-based microparticles containing RK
      and after intravenous (IV) administration of the free drug. The in vitro results
      indicate that the concentrations of feed solution or kind of CH influence the RK
      entrapment and size of microspheres. All formulations increase the solubility of
      this poorly water-soluble drug, but CG is more able to increase the in vitro
      dissolution rate of RK than CH. CG microspheres absorb water quickly and then
      dissolve, whereas CH particles need more volume of water for swelling and
      gelling. In vivo studies showed that, after IV administration, RK is not able to
      cross the blood-brain barrier and to reach the CSF from the bloodstream. On the
      contrary, drug goes to the CSF and the bloodstream only after nasal
      administration of CG microparticles.

PMID- 24081473
TI  - Complex effects of drug/silicate ratio, solid-state equivalent pH, and moisture
      on chemical stability of amorphous quinapril hydrochloride coground with
      silicates.
AB  - The effects of drug/silicate ratio and moisture content on chemical stability of
      amorphous quinapril hydrochloride (QHCl) coground with magnesium
      aluminometasilicates (Neusilin US2 and Neusilin FL2) were investigated. Amorphous
      QHCl/Neusilin samples containing 0-95% (w/w) Neusilin were prepared by
      cryogrinding. All samples were found to be amorphous and remained so for the
      duration of the study. The chemical stability of neat amorphous QHCl and QHCl
      coground with various percentages of Neusilin was studied at 40 degrees C and at
      various moisture contents, as dictated by varying storage relative humidity
      (%RH). QHCl hydrolysis, forming a dicarboxylic acid (DCA) product, slightly
      increased with increasing percentages of Neusilin in the coground amorphous
      samples. On the contrary, QHCl cyclization, forming a diketopiperazine (DKP)
      product, was slow at both lower (e.g., 5%) and higher (e.g., 95%) percentages of
      Neusilin and markedly faster at intermediate percentages (e.g., 50%) of Neusilin.
      This complex effect of drug/silicate ratio on cyclization of quinapril was
      correlated with the surface acidity of the coground amorphous systems. For neat
      amorphous QHCl, increasing moisture resulted in increased DKP and DCA formation,
      as expected. Similarly, higher DCA formation was observed in QHCl/Neusilin
      coground amorphous samples with increasing moisture. However, DKP formation in
      coground amorphous samples was high both at lower (e.g., 0% RH) and higher (e.g.,
      75% RH) humidity, and low at intermediate (e.g., 48% RH) humidity. This complex
      relationship between DKP formation and moisture content for coground amorphous
      samples can be explained by the competitive adsorption of drug and water
      molecules on Neusilin surfaces, which was confirmed by Fourier transform infrared
      (FTIR) spectroscopy. Therefore, drug/silicate ratio, solid-state equivalent pH
      (surface acidity), and moisture have significant effects on chemical stability
      and should be considered in formulation and packaging optimization to develop
      both chemically and physically stable amorphous drug formulations using
      silicates.

PMID- 24081474
TI  - Effect of bile salts on the transport of morphine-6-glucuronide in rat brain
      endothelial cells.
AB  - Bile salts are known to enhance the permeability of biological barriers but
      little is known about their effects on drug permeability across the blood-brain
      barrier (BBB). In this paper, the rat brain endothelial 4 (RBE4) cell monolayer
      incubated with astrocyte-conditioned medium was used as an in vitro model of the
      BBB to investigate the effects of cholate (C), 12-monoketocholate (MKC),
      deoxycholate (DC), and taurocholate (TC) on the transport of the hydrophilic
      drug, morphine-6-glucuronide (M6G). C, MKC, and TC at a concentration of 5 mM
      each and DC at 1 mM increased the permeability of M6G through the paracellular
      pathway based on a similar permeability pattern to that of sucrose. RBE4 cell
      uptake of M6G was unaffected by 5 mM C and TC, whereas 1 mM DC dramatically
      increased it due to an effect shown to be cytotoxicity as measured by the 3-(4,5
      dimethylthiazol-2-yl)-5-(3-carboxymethoxyphenyl)-2-(4-sulfophenyl)-2H-tetrazolium
      assay. Surprisingly, 1 mM MKC significantly increased M6G uptake without any
      cytotoxicity. In summary, all bile salts increased paracellular permeation of M6G
      but MKC also enhanced transcellular transport with little cytotoxicity. MKC
      appears to have the potential to modulate biophysical properties of the cell
      membrane or membrane-bound transporters and may therefore enhance drug delivery
      to the brain.

PMID- 24081475
TI  - Application of melt granulation technology to enhance tabletting properties of
      poorly compactible high-dose drugs.
AB  - Using metformin HCl as the model drug and hydroxypropylcellulose (HPC) as the
      polymeric excipient, a melt granulation (MG) process that employs a twin-screw
      extruder has been developed to enhance compactibility of poorly compactible high
      dose drug substances. A high (90%) drug-load tablet formulation, containing 1025
      mg of active pharmaceutical ingredients and 109 mg of excipients, was produced.
      Drug-polymer-powder mixtures were melt granulated at a temperature above glass
      transition of HPC (130 degrees C) but below melting point of metformin HCl (224
      degrees C). MG was compared with modified wet granulation (WG) and solvent
      granulation (SG) processes. Under identical compression force, the hardness of
      tablets produced was MG>SG>WG and the friability was MG<SG<WG. The hardness of WG
      tablets was highly sensitive to moisture content both during compression and
      subsequent storage, and, although not to the same extent, the hardness of SG
      tablets was also affected by loss-on-drying levels. MG provided a robust
      manufacturing process with highest compactibility and lowest friability that were
      not sensitive to changes in atmospheric moisture level. The process can decrease
      tablet sizes of high-dose drugs and combination products by decreasing the need
      for relatively large amounts of excipients generally used to overcome
      physicochemical limitations of drug substances. (c) 2010 Wiley-Liss, Inc. and the
      American Pharmacists Association J Pharm Sci 100:1553-1565, 2011. 

PMID- 24081476
TI  - Performance-based quality specifications: the relationship between process
      critical control parameters, critical quality attributes, and clinical
      performance.
AB  - The quality of pharmaceutical products is currently evaluated through a series of
      tests that do not explicitly communicate the clinical consequences of product
      variability. A previously published risk simulation platform was used to generate
      quantitative estimates of inefficacy and toxicity for 288 uniform lots of
      extended-release theophylline tablets displaying various levels of content
      uniformity and dissolution variability. These data were used to evaluate the
      univariate specifications utilized in the United States Pharmacopeia (USP) <711>
      and <905>. Simulation revealed that the specifications are too lenient for
      content uniformity, both in terms of inefficacy and toxicity, whereas the
      criteria for dissolution testing are too strict for inefficacy and inaccurate for
      toxicity. The USP tests also failed to pinpoint the clinical interaction between
      content uniformity and dissolution variability. Additionally, the simulation
      platform was used to define the underlying relationship between product quality
      attributes and clinical performance. Here, content uniformity and Weibull
      dissolution time constants were used as inputs to the design spaces, which were
      conditioned on quantitative estimates of inefficacy and toxicity. This
      methodology enhances the information content of the design space by omitting
      quality surrogates (e.g., dissolution, moisture content) that are utilized in
      current design space practices.

PMID- 24081477
TI  - Design of tablets for the delayed and complete release of poorly water-soluble
      weak base drugs using SBE7M-beta-CD as a solubilizing agent.
AB  - The challenge of designing a delayed-release oral dosage form is significantly
      increased when the drug substance is poorly water soluble. This manuscript
      describes the design and characterization of a novel controlled-release film
      coated tablet for the pH-triggered delayed and complete release of poorly water
      soluble weak base drugs. Delivery of weak bases is specifically highlighted with
      the use of dipyridamole and prazosin as model compounds. Tailored delayed release
      is achieved with a combination of an insoluble but semipermeable polymer and an
      enteric polymer, such as cellulose acetate and hydroxypropyl cellulose phthalate,
      respectively, as coatings. The extent of the time lag prior to complete release
      depends on the film-coating composition and thickness. Complete release is
      achieved by the addition of a cyclodextrin, namely SBE7M-beta-CD with or without
      a pH modifier added to the tablet core to ensure complete solubilization and
      release of the drug substance. The film-coating properties allow the complex
      formation/solubilization to occur in situ. Additionally, the drug release rate
      can be modulated on the basis of the cyclodextrin to drug molar ratio. This
      approach offers a platform technology for delayed release of potent but poorly
      soluble drugs and the release can be modulated by adjusting the film-coating
      composition and thickness and/or the cyclodextrin and pH modifier, if necessary.

PMID- 24081478
TI  - Structure determination of monohydrated trifolin (kaempferol 3-O-beta-D
      galactopyranoside) from laboratory powder diffraction data.
AB  - The crystal structure of monohydrated trifolin (kaempferol 3-O-beta-D
      galactopyranoside) (an important biologically active compound, which was isolated
      from the aerial part of Consolida oliveriana) has been determined from
      conventional laboratory X-ray powder diffraction data. Variable counting time
      technique was used during measurement and crystal structure was solved by means
      of Monte Carlo algorithm. The final structure was achieved by Rietveld refinement
      using both constraints and restraints on interatomic bond lengths and angles.

PMID- 24081479
TI  - Scale considerations for selection of saccharide excipients for liquid
      formulations.

PMID- 24081481
TI  - Immunoglobulin injection for the treatment of multiple oral ulcers in Stevens
      Johnson syndrome.
AB  - BACKGROUND: Stevens-Johnson syndrome (SJS) is a rare genetic disorder. The
      syndrome presents with severe purulent conjunctivitis, stomatitis with mucosal
      necrosis, and purpuric macules. This syndrome is associated with hypersensitive
      reaction usually stimulated by infection, vaccination, systemic diseases,
      physical agents, foods or drugs. However, only few cases reported can be related
      to infectious agents, but the causative role of infectious microorganisms seems
      relevant in paediatric patients. Authors want to underline the positive response
      of a new way of therapy by immunoglobulin injection. CASE REPORT: This case
      describes a 10-year-old girl with several erosions disseminated in the oral
      cavity mucosa. The girl had skin erosions that led to the clinical diagnosis of
      SJS. The past medical history of the patient revealed that those symptoms occured
      every 6 months over the last 2 years with 2 consecutive weeks of acute
      manifestations. At that moment, the paediatrician decided for cortisone
      administration in order to manage the acute symptoms, but after 6 months a new
      acute episode was observed. For this reason the patient was referred to the
      Department of Genetics and Immunological Paediatrics. TREATMENT: Oral ulcers had
      been topically treated with an oral balance gel. Intravenous injection of
      immunoglobulin was then applied and the patient was discharged after 5 days of
      treatment with the total symptoms in remission. FOLLOW-UP: The patient was
      followed up 3 monthly over the next 24 months. At that time no relapse of the SJS
      was observed. CONCLUSION: The seriousness of this condition imposes a prompt
      recognition. Paediatric dentists should recognise the clinical signs of possible
      SJS as soon as possible in order to perform a quick diagnosis and initiate
      treatment.

PMID- 24081483
TI  - Chronic granulomatous disease: a 25-year patient registry based on a multistep
      diagnostic procedure, from the referral center for primary immunodeficiencies in
      Greece.
AB  - Chronic Granulomatous Disease (CGD) is an uncommon primary immunodeficiency
      caused by the absence or dysfunction of one of NADPH oxidase subunits, with
      heterogeneous genetic aetiologies. The aim of this study was the CGD patient
      registry in Greece, the identification of the responsible genotype and the
      potential correlation with the patient's clinical phenotype. Medical charts of 24
      CGD patients, investigated by NBT test or DHR for NADPH oxidase activity, Western
      blot analysis for NADPH oxidase component expression and DNA sequencing (pyro-
      and cycle sequencing) for mutation analysis, were reviewed. All patients, but
      one, were classified into the different types of CGD. Sixteen patients from 14
      unrelated families had X-linked CGD (66.7 %), four had mutations in the NCF1 gene
      (19 %), and three, from two unrelated families, had mutations in NCF2 (9.5 %)
      [Corrected]. Fifteen mutations were detected in the CYBB gene, including nonsense
      (53.8 %), splice site (30.8 %) and missense mutations (7.7 %), and deletions (7.7
      %). Two novel mutations were identified; one in CYBB and one in NCF1. Carrier
      detection for X-CGD revealed that the de novo mutation rate was about 7 %.
      Prenatal diagnosis identified one affected male in three male fetuses tested. In
      both the X-linked and the autosomal recessive (AR-CGD) group, the
      gastrointestinal and respiratory manifestations were more common, followed by
      lympadenopathy in X-CGD and skin infections in the AR-CGD group. The patients
      with a mutation in CYBB had a wider variability of clinical manifestations and
      earlier diagnosis (4.6 years) compared to the AR-CGD group (12.9 years). The
      incidence of CGD in Greece is estimated at 0.90 (95 % CI 0.89-0.91) per 100,000
      live births for the last decade.

PMID- 24081484
TI  - Recipient leukocyte infusion enhances the local and systemic graft-versus
      neuroblastoma effect of allogeneic bone marrow transplantation in mice.
AB  - Allogeneic hematopoietic stem cell transplantation and donor leukocyte infusion
      (DLI) may hold potential as a novel form of immunotherapy for high-risk
      neuroblastoma. DLI, however, carries the risk of graft-versus-host disease
      (GvHD). Recipient leukocyte infusion (RLI) induces graft-versus-leukemia
      responses without GvHD in mice and is currently being explored clinically. Here,
      we demonstrate that both DLI and RLI, when given to mixed C57BL/6->A/J radiation
      chimeras carrying subcutaneous Neuro2A neuroblastoma implants, can slow the local
      growth of such tumors. DLI provoked full donor chimerism and GvHD; RLI produced
      graft rejection but left mice healthy. Flow cytometric studies showed that the
      chimerism of intratumoral leukocytes paralleled the systemic chimerism. This was
      associated with increased CD8/CD4 ratios, CD8+ T-cell IFN-gamma expression and NK
      cell Granzyme B expression within the tumor, following both DLI and RLI. The
      clinically safe anti-tumor effect of RLI was further enhanced by adoptively
      transferred naive recipient-type NK cells. In models of intravenous Neuro2A tumor
      challenge, allogeneic chimeras showed superior overall survival over syngeneic
      chimeras. Bioluminescence imaging in allogeneic chimeras challenged with
      luciferase-transduced Neuro2A cells showed both DLI and RLI to prolong metastasis
      free survival. This is the first experimental evidence that RLI can safely
      produce a local and systemic anti-tumor effect against a solid tumor. Our data
      indicate that RLI may provide combined T-cell and NK-cell reactivity effectively
      targeting Neuro2A neuroblastoma.

PMID- 24081485
TI  - The feasibility of a 64-slice MDCT for detection of the Adamkiewicz artery:
      comparison of the detection rate of intravenous injection CT angiography using a
      64-slice MDCT versus intra-arterial and intravenous injection CT angiography
      using a 16-slice MDCT.
AB  - Identification of the Adamkiewicz artery (AKA) using CT angiography (CTA) is
      crucial in patients with thoracic aortic aneurysm (TAA) or aortic dissection
      (AD). The purpose of this study was to compare the AKA detection rate of
      intravenous injection with a 64-slice MDCT (IV64) versus a 16-slice MDCT (IV16)
      as well as by CTA using intra-arterial injection with a 16-slice MDCT (IA16). A
      retrospective review of 160 consecutive patients who underwent CTA was performed.
      There were 108 TAA and 52 AD cases, 105 of whom were examined with IV64, 15 with
      IV16, and 40 with IA16. The AKA detectability for each imaging method was
      assessed, and the factors influencing the detectability were analyzed by
      multivariate analysis. The detection rates for IV64, IV16, and IA16 were 85.7,
      60.0, and 80.0 %, respectively, with IV64 being more sensitive than IV16 (P =
      0.025). The detection rate for AD patients was 66.7 % with IV64, which was
      similar to IV16 (57.1 %) and IA16 (66.8 %). On the other hand, the detection rate
      for TAA patients was 93.3 % with IV64, which was higher than IV16 (62.5 %, P =
      0.021) and similar to IA16 (88.0 %). Multivariate analysis demonstrated the
      independent factors for AKA detectability were TAA versus AD (P = 0.005, Odds
      ratio = 3.98) and IV64 versus IV16 (P = 0.037, Odds ratio = 4.03). The detection
      rate was higher for IV64 than for IV16, especially for TAA patients, while the
      rate was similar between IV64 and invasive IA16. A 64-slice MDCT thus provides a
      less invasive visualization of the AKA.

PMID- 24081482
TI  - Algal photoreceptors: in vivo functions and potential applications.
AB  - Many algae, particularly microalgae, possess a sophisticated light-sensing system
      including photoreceptors and light-modulated signaling pathways to sense
      environmental information and secure the survival in a rapidly changing
      environment. Over the last couple of years, the multifaceted world of algal
      photobiology has enriched our understanding of the light absorption mechanisms
      and in vivo function of photoreceptors. Moreover, specific light-sensitive
      modules have already paved the way for the development of optogenetic tools to
      generate light switches for precise and spatial control of signaling pathways in
      individual cells and even in complex biological systems. 

PMID- 24081486
TI  - Orthogonal bone plate stabilization for limb-sparing surgery.
AB  - This report describes limb-sparing surgery in a 35 kg, six-year-old Hungarian
      Vizsla with a distal radial lytic bone lesion. Preoperative biopsy had suggested
      a bone cyst, however histopathology on the excised bone segment was indicative of
      an osteosarcoma. Following excision of the tumour, the bone defect was filled
      with a composite bone graft and stabilized with a custom-made dorsal 3.5/2.7 mm
      pancarpal arthrodesis plate and an orthogonally positioned medial 2.7 mm
      compression plate. This technique has not previously been described for limb
      sparing procedures. No complications were encountered, and despite the owners
      declining adjunctive chemotherapy, the dog was alive 34 months postoperatively
      with near normal limb function. 

PMID- 24081487
TI  - Michael Sixt: love the way they move. Sixt studies the mechanisms of leukocyte
      locomotion.

PMID- 24081488
TI  - Cell biology in neuroscience: RNA-based mechanisms underlying axon guidance.
AB  - Axon guidance plays a key role in establishing neuronal circuitry. The motile
      tips of growing axons, the growth cones, navigate by responding directionally to
      guidance cues that pattern the embryonic neural pathways via receptor-mediated
      signaling. Evidence in vitro in the last decade supports the notion that RNA
      based mechanisms contribute to cue-directed steering during axon guidance.
      Different cues trigger translation of distinct subsets of mRNAs and localized
      translation provides precise spatiotemporal control over the growth cone proteome
      in response to localized receptor activation. Recent evidence has now
      demonstrated a role for localized translational control in axon guidance
      decisions in vivo. 

PMID- 24081489
TI  - PLP inhibits the activity of interphase centrosomes to ensure their proper
      segregation in stem cells.
AB  - Centrosomes determine the mitotic axis of asymmetrically dividing stem cells.
      Several studies have shown that the centrosomes of the Drosophila melanogaster
      central brain neural stem cells are themselves asymmetric, organizing varying
      levels of pericentriolar material and microtubules. This asymmetry produces one
      active and one inactive centrosome during interphase. We identify pericentrin
      like protein (PLP) as a negative regulator of centrosome maturation and activity.
      We show that PLP is enriched on the inactive interphase centrosome, where it
      blocks recruitment of the master regulator of centrosome maturation, Polo kinase.
      Furthermore, we find that ectopic Centrobin expression influenced PLP levels on
      the basal centrosome, suggesting it may normally function to regulate PLP.
      Finally, we conclude that, although asymmetric centrosome maturation is not
      required for asymmetric cell division, it is required for proper centrosome
      segregation to the two daughter cells. 

PMID- 24081490
TI  - Analysis of the local organization and dynamics of cellular actin networks.
AB  - Actin filaments, with the aid of multiple accessory proteins, self-assemble into
      a variety of network patterns. We studied the organization and dynamics of the
      actin network in nonadhesive regions of cells bridging fibronectin-coated
      adhesive strips. The network was formed by actin nodes associated with and linked
      by myosin II and containing the formin disheveled-associated activator of
      morphogenesis 1 (DAAM1) and the cross-linker filamin A (FlnA). After Latrunculin
      A (LatA) addition, actin nodes appeared to be more prominent and demonstrated
      drift-diffusion motion. Superresolution microscopy revealed that, in untreated
      cells, DAAM1 formed patches with a similar spatial arrangement to the actin
      nodes. Node movement (diffusion coefficient and velocity) in LatA-treated cells
      was dependent on the level and activity of myosin IIA, DAAM1, and FlnA. Based on
      our results, we developed a computational model of the dynamic formin-filamin
      actin asters that can self-organize into a contractile actomyosin network. We
      suggest that such networks are critical for connecting distant parts of the cell
      to maintain the mechanical coherence of the cytoplasm.

PMID- 24081491
TI  - Recruitment of folliculin to lysosomes supports the amino acid-dependent
      activation of Rag GTPases.
AB  - Birt-Hogg-Dube syndrome, a human disease characterized by fibrofolliculomas (hair
      follicle tumors) as well as a strong predisposition toward the development of
      pneumothorax, pulmonary cysts, and renal carcinoma, arises from loss-of-function
      mutations in the folliculin (FLCN) gene. In this study, we show that FLCN
      regulates lysosome function by promoting the mTORC1-dependent phosphorylation and
      cytoplasmic sequestration of transcription factor EB (TFEB). Our results indicate
      that FLCN is specifically required for the amino acid-stimulated recruitment of
      mTORC1 to lysosomes by Rag GTPases. We further demonstrated that FLCN itself was
      selectively recruited to the surface of lysosomes after amino acid depletion and
      directly bound to RagA via its GTPase domain. FLCN-interacting protein 1 (FNIP1)
      promotes both the lysosome recruitment and Rag interactions of FLCN. These new
      findings define the lysosome as a site of action for FLCN and indicate a critical
      role for FLCN in the amino acid-dependent activation of mTOR via its direct
      interaction with the RagA/B GTPases. 

PMID- 24081492
TI  - Synaptic mutant huntingtin inhibits synapsin-1 phosphorylation and causes
      neurological symptoms.
AB  - Many genetic mouse models of Huntington's disease (HD) have established that
      mutant huntingtin (htt) accumulates in various subcellular regions to affect a
      variety of cellular functions, but whether and how synaptic mutant htt directly
      mediates HD neuropathology remains to be determined. We generated transgenic mice
      that selectively express mutant htt in the presynaptic terminals. Although it was
      not overexpressed, synaptic mutant htt caused age-dependent neurological symptoms
      and early death in mice as well as defects in synaptic neurotransmitter release.
      Mass spectrometry analysis of synaptic fractions and immunoprecipitation of
      synapsin-1 from HD CAG150 knockin mouse brains revealed that mutant htt binds to
      synapsin-1, a protein whose phosphorylation is critical for neurotransmitter
      release. We found that polyglutamine-expanded exon1 htt binds to the C-terminal
      region of synapsin-1 to reduce synapsin-1 phosphorylation. Our findings point to
      a critical role for synaptic htt in the neurological symptoms of HD, providing a
      new therapeutic target. 

PMID- 24081494
TI  - Confirmation of the presence of squalene in human eyelid lipid by heteronuclear
      single quantum correlation spectroscopy.
AB  - (1)H-NMR spectroscopy has been used to quantify squalene in meibum and sebum.
      Squalene has many beneficial properties and its loss on the surface of skin upon
      ultraviolet light exposure or in the tear film with dry eye could be detrimental.
      In this study, we confirm the NMR proton resonance assignments of squalene,
      squalene in human meibum, and in human eyelid lipid using heteronuclear single
      quantum correlation spectroscopy. Our results confirm the presence of squalene in
      eyelid lipid. We speculate that the squalene in eyelid lipid could be secreted
      from sebaceous glands. The NMR resonances between 5.2 and 5.0 ppm, characteristic
      of the =CH of squalene, were resolved in the spectrum of human meibum and used to
      estimate that 1 % or less of squalene is present in meibum. However, the
      resonance assignments of squalene in meibum were not confirmed. The
      characteristics of squalene including its anti-inflammatory, antioxidant, and
      antibacterial qualities suggest that the presence of a squalene film is
      beneficial. Its loss in human meibum from patients with dry eye could be
      detrimental and contribute to the symptoms observed in these patients.

PMID- 24081493
TI  - Dietary linoleic acid elevates the endocannabinoids 2-AG and anandamide and
      promotes weight gain in mice fed a low fat diet.
AB  - Dietary intake of linoleic acid (LNA, 18:2n-6) has increased dramatically during
      the 20th century and is associated with greater prevalence of obesity. The
      endocannabinoid system is involved in regulation of energy balance and a
      sustained hyperactivity of the endocannabinoid system may contribute to obesity.
      Arachidonic acid (ARA, 20:4n-6) is the precursor for 2-AG and anandamide (AEA),
      and we sought to determine if low fat diets (LFD) could be made obesogenic by
      increasing the endocannabinoid precursor pool of ARA, causing excessive
      endocannabinoid signaling leading to weight gain and a metabolic profile
      associated with obesity. Mice (C57BL/6j, 6 weeks of age) were fed 1 en% LNA and 8
      en% LNA in low fat (12.5 en%) and medium fat diets (MFD, 35 en%) for 16 weeks. We
      found that increasing dietary LNA from 1 to 8 en% in LFD and MFD significantly
      increased ARA in phospholipids (ARA-PL), elevated 2-AG and AEA in liver, elevated
      plasma leptin, and resulted in larger adipocytes and more macrophage infiltration
      in adipose tissue. In LFD, dietary LNA of 8 en% increased feed efficiency and
      caused greater weight gain than in an isocaloric reduction to 1 en% LNA.
      Increasing dietary LNA from 1 to 8 en% elevates liver endocannabinoid levels and
      increases the risk of developing obesity. Thus a high dietary content of LNA (8
      en%) increases the adipogenic properties of a low fat diet. 

PMID- 24081495
TI  - Genetic polymorphisms in the APOA1 gene and their relationship with serum HDL
      cholesterol levels.
AB  - Low high density lipoprotein cholesterol (HDL-C) is a known risk factor of
      coronary artery disease. Apolipoprotein A1 (APOA1) is the most abundant component
      of HDL-C. This study aimed at identifying sequence variations (rare and common)
      in the APOA1 gene and its association with serum HDL-C levels. This study was
      conducted from April 2012 to February 2013 on 79 Tehranians (participants of
      Tehran Lipid and Glucose Study) with extremely low HDL-C (within the 5th
      percentile) and 63 individuals with extremely high HDL-C (within the 95th
      percentile) levels. After DNA amplification by PCR, DNA sequencing of all three
      exons and 700 bps of promoter region of the APOA1 gene was performed. Sequence
      results were analyzed and interpreted using the appropriate software and variants
      were identified. After sequencing 42 common and rare variants were identified, 11
      of which were known variants and the others had been unreported so far. Of the
      exonic variants, 11 were missense, 6 were synonymous and 1 was nonsense. There
      was a significant association between serum HDL-C and variant of rs2070665 as
      well as variants Chr.11:116707788, Chr.11:116708059, Chr.11:116708036,
      Chr.11:116707729, rs201148448, Chr.11:116707018, Chr.11:116707801,
      Chr.11:116708530, Chr.11:116708088, rs121912724 and Chr.11:116706966 (p < 0.001).
      Variants Chr.11:116707018, rs121912724 and 2070665 were independent predictors of
      the HDL-C level (p < 0.001). SNP Chr.11:116707018 was the strongest predictor of
      the HDL-C level (OR 7.527, p < 0.001). This study identified 42 variants in APOA1
      gene, 31 of which were new variants. Three variants of rs2070665, rs121912724 and
      Chr.11:116707018 could predict the HDL-C level independently. Variant rs2070665
      was protective against low-HDL-C levels while variants rs121912724 and
      Chr.11:116707018 were risk factors for that in our population.

PMID- 24081496
TI  - Dutch guidelines for physiotherapy in patients with stress urinary incontinence:
      an update.
AB  - INTRODUCTION AND HYPOTHESIS: Stress urinary incontinence (SUI) is the most common
      form of incontinence impacting on quality of life (QOL) and is associated with
      high financial, social, and emotional costs. The purpose of this study was to
      provide an update existing Dutch evidence-based clinical practice guidelines
      (CPGs) for physiotherapy management of patients with stress urinary incontinence
      (SUI) in order to support physiotherapists in decision making and improving
      efficacy and uniformity of care. MATERIALS AND METHODS: A computerized literature
      search of relevant databases was performed to search for information regarding
      etiology, prognosis, and physiotherapy assessment and management in patients with
      SUI. Where no evidence was available, recommendations were based on consensus.
      Clinical application of CPGs and feasibility were reviewed. The diagnostic
      process consists of systematic history taking and physical examination supported
      by reliable and valid assessment tools to determine physiological potential for
      recovery. Therapy is related to different problem categories. SUI treatment is
      generally based on pelvic floor muscle exercises combined with patient education
      and counseling. An important strategy is to reduce prevalent SUI by reducing
      influencing risk factors. RESULTS: Scientific evidence supporting assessment and
      management of SUI is strong. CONCLUSIONS: The CPGs reflect the current state of
      knowledge of effective and tailor-made intervention in SUI patients.

PMID- 24081497
TI  - Changes in prolapse surgery trends relative to FDA notifications regarding
      vaginal mesh.
AB  - INTRODUCTION AND HYPOTHESIS: In 2008 and 2011, the US Food and Drug
      Administration (FDA) released notifications regarding vaginal mesh. In describing
      prolapse surgery trends over time, we predicted vaginal mesh use would decrease
      and native tissue repairs would increase. METHODS: Operative reports were
      reviewed for all prolapse repairs performed from 2008 to 2011 at our large
      regional hospital system. The number of each type of prolapse repair was
      determined per quarter year and expressed as a percentage of all repairs.
      Surgical trends were examined focusing on changes with respect to the release of
      two FDA notifications. We used linear regression to analyze surgical trends and
      chi-square for demographic comparisons. RESULTS: One thousand two hundred and
      eleven women underwent 1,385 prolapse procedures. Mean age was 64 +/- 12, and 70
      % had stage III prolapse. Vaginal mesh procedures declined over time (p = 0.001),
      comprising 27 % of repairs in early 2008, 15 % at the first FDA notification, 5 %
      by the second FDA notification, and 2 % at the end of 2011. The percentage of
      native tissue anterior/posterior repairs (p < 0.001) and apical suspensions (p =
      0.007) increased, whereas colpocleisis remained constant (p = 0.475). Despite an
      overall decrease in open sacral colpopexies (p < 0.001), an initial increase was
      seen around the first FDA notification. We adopted laparoscopic/robotic
      techniques around this time, and the percentage of minimally invasive sacral
      colpopexies steadily increased thereafter (p < 0.001). All sacral colpopexies
      combined as a group declined over time (p = 0.011). CONCLUSIONS: Surgical
      treatment of prolapse continues to evolve. Over a 4-year period encompassing two
      FDA notifications regarding vaginal mesh and the introduction of
      laparoscopic/robotic techniques, we performed fewer vaginal mesh procedures and
      more native tissue repairs and minimally invasive sacral colpopexies.

PMID- 24081498
TI  - Surface control of blastospore attachment and ligand-mediated hyphae adhesion of
      Candida albicans.
AB  - Adhesion on a surface via nonspecific attachment or multiple ligand-receptor
      interactions is a critical event for fungal infection by Candida albicans. Here,
      we find that the tri(ethylene glycol)- and d-mannitol-terminated monolayers do
      not resist the blastospore attachment, but prevent the hyphae adhesion of C.
      albicans. The hyphae adhesion can be facilitated by tripeptide sequences of
      arginine-glycine-aspartic acid (RGD) covalently decorated on a background of
      tri(ethylene glycol)-terminated monolayers. This adhesion mediated by selected
      ligands is sensitive to the scrambling of peptide sequences, and is inhibited by
      the presence of cyclic RGD peptides in the solution. 

PMID- 24081499
TI  - Role of interleukin 28-B in the spontaneous and treatment-related clearance of
      HCV infection in patients with chronic HBV/HCV dual infection.
AB  - The purpose of this investigation was to evaluate the role of IL28-B polymorphism
      in the clearance of hepatitis C virus (HCV) in chronic hepatitis B virus
      (HBV)/HCV coinfection during a long-term follow-up. Thirty-four consecutive
      patients with HBV surface antigen (HBsAg)-positive/anti-HCV-positive chronic
      hepatitis were retrospectively enrolled at their first liver biopsy (LB). For all
      patients, a documented clinical, serological and virological follow-up of at
      least 3 years (range 3-16 years) after LB and a sample of whole blood for genetic
      evaluation were available. Of the 24 patients with detectable serum HBV-DNA and
      HCV-RNA at their first observation, three cleared both HBV-DNA and HCV-RNA, 12
      HCV-RNA and five HBV-DNA. Of the seven HBV DNA-positive/HCV RNA-negative patients
      at enrolment, three cleared HBV-DNA and one remained HBV DNA-positive and became
      HCV RNA-positive. All three HBV DNA-negative/HCV RNA-positive patients remained
      unchanged. Compared with the 12 patients with HCV persistence, the 15 patients
      who cleared HCV were younger, had lower serum alanine aminotransferase (ALT), HCV
      load, and histological activity index (HAI) and fibrosis score, more frequently
      had IL28-B CC variant, had been receiving an interferon-based treatment and less
      frequently cleared serum HBV-DNA. To investigate the relationship between the
      IL28-B variants and clearance of HCV, excluding the confounding effect of
      interferon-based treatment, the Mantel-Haenszel test was used, which indicated an
      association between HCV clearance and IL28-B variants (p = 0.009). In chronic
      HBV/HCV coinfection, a long-term follow-up showed a frequent spontaneous or
      treatment-related clearance of active replication of one or both viruses and
      identified the IL28-B CC genotype as an independent predictor of HCV clearance.

PMID- 24081500
TI  - Zig Zag versus Top Hat configuration in IntraLase-enabled penetrating
      keratoplasty.
AB  - AIM: To compare the outcomes with IntraLase-enabled keratoplasty using (IEK) Top
      Hat (TH) versus Zig Zag (ZZ) configuration. METHODS: Retrospective comparative
      series of 24 eyes that underwent TH and 10 eyes that underwent ZZ IEK. RESULTS:
      There were no significant differences in LogMar Best-spectacle corrected visual
      acuity (TH- IEK=0.3; ZZ-IEK=0.18, p=0.18), spherical equivalent (TH-IEK=-3.55+/
      3.7 dioptres (D); ZZ-IEK=-2.69+/-4.85 D, p=0.60), manifest cylinder (TH-
      IEK=3.79+/-2.43 D; ZZ- IEK=4.61+/-3.29 D, p=0.45), topographic astigmatism (TH
      IEK=3.67+/-2.34 D; ZZ-IEK=4.26+/-1.1 D, p=0.63), total higher-order aberrations
      (TH- IEK=8.26+/-3.53; ZZ-IEK=8.1+/-4.71, P=0.92), endothelial cell density change
      from baseline (TH- IEK= -41.55%+/-15.86; ZZ-IEK=-25.45%+/-30.66, p=0.22) or time
      to suture removal in months (TH- IEK=7.48+/-4.07; ZZ- IEK=6.93+/-2.71, p=0.75).
      There was no difference in requirements for astigmatic keratectomy (TH
      IEK=54.2%+/-13; ZZ-IEK=50%+/-5, OR=1.18) or complications (TH-IEK=25%+/-6; ZZ
      IEK=30%+/-3, OR=0.78). CONCLUSIONS: TH-IEK and ZZ-IEK have comparable visual and
      refractive outcomes, wound healing and endothelial cell counts at 1-year.

PMID- 24081501
TI  - Comparison of three-dimensional optical coherence tomography and combining a
      rotating Scheimpflug camera with a Placido topography system for forme fruste
      keratoconus diagnosis.
AB  - OBJECTIVE: To evaluate the ability of parameters measured by three-dimensional
      (3D) corneal and anterior segment optical coherence tomography (CAS-OCT) and a
      rotating Scheimpflug camera combined with a Placido topography system
      (Scheimpflug camera with topography) to discriminate between normal eyes and
      forme fruste keratoconus. METHODS: Forty-eight eyes of 48 patients with
      keratoconus, 25 eyes of 25 patients with forme fruste keratoconus and 128 eyes of
      128 normal subjects were evaluated. Anterior and posterior keratometric
      parameters (steep K, flat K, average K), elevation, topographic parameters,
      regular and irregular astigmatism (spherical, asymmetry, regular and higher-order
      astigmatism) and five pachymetric parameters (minimum, minimum-median, inferior
      superior, inferotemporal-superonasal, vertical thinnest location of the cornea)
      were measured using 3D CAS-OCT and a Scheimpflug camera with topography. The area
      under the receiver operating curve (AUROC) was calculated to assess the
      discrimination ability. Compatibility and repeatability of both devices were
      evaluated. RESULTS: Posterior surface elevation showed higher AUROC values in
      discrimination analysis of forme fruste keratoconus using both devices. Both
      instruments showed significant linear correlations (p<0.05, Pearson's correlation
      coefficient) and good repeatability (ICCs: 0.885-0.999) for normal and forme
      fruste keratoconus. CONCLUSIONS: Posterior elevation was the best discrimination
      parameter for forme fruste keratoconus. Both instruments presented good
      correlation and repeatability for this condition.

PMID- 24081503
TI  - Cluster of Urrets-Zavalia syndrome: a sequel of toxic anterior segment syndrome.

PMID- 24081502
TI  - Diagnostic ability of a new method for measuring haemoglobin levels in the optic
      nerve head in multiple sclerosis patients.
AB  - AIMS: To evaluate a new method for measuring haemoglobin (Hb) levels and
      quantifying the colour changes in the optic nerve head of multiple sclerosis (MS)
      patients to detect axonal loss and consequently optic disc atrophy. MATERIAL AND
      METHODS: 40 MS patients and 40 age and sex-matched healthy subjects were included
      in this prospective cross-sectional study and underwent a full ophthalmological
      examination, including three photographs of the optic disc. The Laguna ONhE
      ('optic nerve hemoglobin'; Insoft SL, Tenerife, Spain) software was used to
      obtain the Hb analysis in each of the 24 sectors and average Hb of optic disc
      photographs acquired. Reproducibility of measurements provided by Laguna ONhE
      program was analysed. RESULTS: MS patients showed significant reduction of optic
      disc Hb percentages in average Hb (58.99% in MS, 65.39% in healthy subjects;
      p<0.001) and in almost all analysed sectors with the largest differences in
      temporal sectors. Laguna ONhE program showed good reproducibility measuring Hb
      percentages in MS patients and healthy subjects. CONCLUSIONS: Measurements of
      optic disc Hb levels obtained with Laguna ONhE software had good ability
      detecting optic atrophy and axonal loss in MS patients. This method had good
      reliability and is easy to implement in routine clinical practice.

PMID- 24081504
TI  - Dual immunostaining of cervical cytology specimens with atypical squamous cells
      for p16/Ki-67 does not exclude the existence of a high-grade squamous
      intraepithelial lesion.
AB  - This study was conducted to evaluate the accuracy of p16/Ki-67 dual
      immunostaining compared to high-risk human papillomavirus (HR-HPV) DNA testing
      for cervical intraepithelial neoplasia (CIN) in women with atypical squamous
      cells, cytology not excluding high-grade squamous intraepithelial lesion (ASC-H).
      Data were collected from 73 patients diagnosed to have ASC-H on a Pap smear who
      were HPV genotyped and had histological examination of a cervical biopsy. The
      CINtecPLUS kit was used on residual liquid-based material, and the
      immunoreactivity of dual-stained cells was graded according to the number as
      follows: G1 (1-5 positive cells), G2 (6-10), G3 (11-20), and G4 (> 20). Accuracy
      was evaluated based on the histological examination of colposcopy-guided biopsy
      or cervical conization on follow-up. Of the 70 patients with available data,
      positive p16/Ki-67 was associated with histological severity as follows: 15% in
      negative histology, 67% in CIN 1, 90% in CIN 2, and 100% in CIN 3. The average
      grade of positive p16/Ki-67 staining also increased from 0.2 in histologically
      negative cases to 1.2 in CIN 1, 2.4 in CIN 2, and 2.9 in CIN 3 (p < 0.01). For
      patients with CIN 2 or higher, p16/Ki-67 had a sensitivity of 94.6% and a
      specificity of 75.8%, while HR-HPV testing showed a sensitivity of 67.6% and a
      specificity of 66.7%. p16/Ki-67 immunostaining demonstrated better accuracy than
      HR-HPV for detecting CIN 2 or higher in patients with ASC-H cytology. Given the
      higher concordance with histological diagnosis, the grading system of positive
      p16/Ki-67 can be a useful adjunct for predicting high-grade lesions in clinical
      practice.

PMID- 24081505
TI  - Application of X-ray grating interferometry for the imaging of joint structures.
AB  - Conventional X-ray absorption contrast imaging does not depict soft tissues, such
      as cartilage, in sufficient detail. For visualization of the soft tissues, X-ray
      phase-contrast imaging is more sensitive than absorption-contrast imaging. The
      basic concept of the X-ray phase-contrast imaging used in this study is similar
      to that of differential interference contrast (Nomarski) microscopy. We applied
      Talbot-Lau X-ray interferometry to visualize the joint structures in the right
      hand and knee of a donated cadaver. This imaging system simultaneously produced
      three different types of images: an absorption image, a differential phase image,
      and a visibility image. The interface between the articular cartilage of the
      metacarpo-phalangeal joint and fluid or the bony cortex was clearly demonstrated
      on the differential phase image, whereas this interface was unclear on the
      absorption image. Within the knee joint, the surface of the articular cartilage
      was demonstrated both on the differential phase and visibility images; the medial
      collateral ligament and medial meniscus were also visualized successfully. These
      results are clinically significant for the diagnosis and therapeutic estimation
      of rheumatoid arthritis and related joint diseases. This feasibility study on the
      clinical application of this imaging tool was a collaborative effort of
      researchers in the fields of physics, radiology, and gross anatomy.

PMID- 24081507
TI  - MBMD coping styles and psychiatric indicators and response to a multidisciplinary
      pain treatment program.
AB  - Psychosocial and personality factors are known to contribute to the maintenance
      of and recovery from chronic pain conditions but less is known about their
      influence on the efficacy of pain treatment programs. The purpose of the present
      study is to examine the ability of the Millon Behavioral Medicine Diagnostic
      (MBMD), a broadband measure of personality and psychosocial characteristics, to
      predict response to multidisciplinary pain treatment. 93 patients completed the
      MBMD, and ratings of current pain and average pain on an 11 point scale, prior to
      a multidisciplinary pain management program. Ratings of current and average pain
      were completed upon program completion. Participants were classified as
      "successful" or "unsuccessful" program completers based on pain reductions of >=2
      points. After program completion, 47 % of participants evidenced successful pain
      reductions. These successful participants had lower scores on depression and on
      coping style scales measuring introversive, inhibited, and dejected tendencies at
      baseline. Additionally, lower pre-treatment depression scores and lower scores on
      each of these coping style scales predicted lower pain ratings at discharge
      independent of educational level and pre-treatment pain ratings. The MBMD may be
      a useful tool to delineate patients who are likely to make significant treatment
      gains in intense, multidisciplinary pain treatment programs.

PMID- 24081508
TI  - Report of the clinical donor case workshop of the European Association of Tissue
      Banks annual meeting 2012.
AB  - The European Association of Tissue Banks (EATB) donor case workshop is a forum
      held within the program of the EATB annual congress. The workshop offers an
      opportunity to discuss and evaluate approaches taken to challenging situations
      regarding donor selection, it promotes consensus development in deciding tissue
      donor acceptability when donor health issues are not addressed in standards and
      regulations, and serves to strengthen the professional tissue banking networks
      across Europe and beyond. This report reflects some of the discussion at the
      workshop during the annual congress in Vienna in 2012. The cases presented dealt
      with problems encountered by tissue bank facilities concerning idiopathic
      thrombocytopenia and auto-immune disorders, hemodilution and blood sample
      identification, premalignant and malignant lesions, and Huntington's disease. The
      discussions during the workshop demonstrate that the implications on the safety
      of tissue transplantation of various tissue donor illnesses, physical findings
      and behaviours, and the preventive measures taken by tissue facilities, may not
      always be agreed by tissue facility medical directors and other professionals.
      Moreover, they reveal that operating procedures, regulations and standards cannot
      comprehensively cover all tissue donor findings, medical histories and
      circumstances surrounding the cause of death. For many of the issues raised,
      there is a need for scientific research to provide a better evidence base for
      future deliberations about the suitability and eligibility of tissue allograft
      donors. 

PMID- 24081509
TI  - Added value of trabecular bone score over bone mineral density for identification
      of vertebral fractures in patients with areal bone mineral density in the non
      osteoporotic range.
AB  - Detection of patients with vertebral fracture is similar for areal bone mineral
      density (aBMD) and trabecular bone score (TBS) in patients with non-vertebral
      fracture. In non-osteoporotic patients, TBS adds information to lumbar spine aBMD
      and is related to an index of spine deterioration. INTRODUCTION: Vertebral
      fractures (VFs) are more predictive of future fracture than aBMD. The number and
      severity of VFs are related to microarchitecture deterioration. TBS has been
      shown to be related to microarchitecture. The study aimed at evaluating TBS in
      the prediction of the presence and severity of VFs. METHODS: Patients were
      selected from a Fracture Liaison Service (FLS): aBMD and vertebral fracture
      assessment (VFA) were assessed after the fracture, using dual-energy X-ray
      absorptiometry (DXA). VFs were classified using Genant's semiquantitative method
      and severity, using the spinal deformity index (SDI). TBS was obtained after
      analysis of DXA scans. Performance of TBS and aBMD was assessed using areas under
      the curves (AUCs). RESULTS: A total of 362 patients (77.3% women; mean age 74.3
      +/- 11.7 years) were analysed. Prevalence of VFs was 36.7%, and 189 patients
      (52.2%) were osteoporotic. Performance of TBS was similar to lumbar spine (LS)
      aBMD and hip aBMD for the identification of patients with VFs. In the population
      with aBMD in the non-osteoporotic range (n = 173), AUC of TBS for the
      discrimination of VFs was higher than the AUC of LS aBMD (0.670 vs 0.541, p =
      0.035) but not of hip aBMD; there was a negative correlation between TBS and SDI
      (r = -0.31; p < 0.0001). CONCLUSION: Detection of patients with vertebral
      fracture is similar for aBMD and TBS in patients with non-vertebral fracture. In
      patients with aBMD in the non-osteoporotic range, TBS adds information to lumbar
      spine aBMD alone and is related to an index of spine deterioration.

PMID- 24081510
TI  - Molecular alterations of bone quality in sequesters of bisphosphonates-related
      osteonecrosis of the jaws.
AB  - Compared to healthy bone, the intrinsic bone materials properties in the pre
      existing lamellar bone are altered in jaw bone sequesters of bisphosphonates (BP)
      related osteonecrosis. INTRODUCTION: The aim of this study was to evaluate the
      human jaw bone quality, especially intrinsic bone material properties among
      sequesters of osteonecrosis of the jaw (ONJ) induced by BP. METHODS: Bone
      sequesters were obtained from 24 patients suffering from ONJ following a BP
      treatment. Within BP-exposed bone samples, benign-BP and malignant-BP groups were
      distinguished in relation to the underlying disease: osteoporosis and bone
      metastases or multiple myeloma, respectively. Healthy cadaveric cortical jaw bone
      samples were used as controls. The physicochemical parameters of bone samples -
      mineral/organic ratio, relative proteoglycan content, crystallinity, monohydrogen
      phosphate content, and type-B carbonate substitution - were evaluated by Raman
      microspectroscopy. Representative Raman spectral features of bones control and BP
      exposed bone sequesters were identified with the Partial-Least-Square
      Discriminant Analysis (PLS-DA). RESULTS: BP-exposed bone sequesters are
      characterized by a significant increase of mineral to organic ratio (+12 %) and a
      significant decrease of relative proteoglycan content (-35 %), thus regulating
      initial collagen matrix mineral deposition. Structural changes on mineral
      components are revealed by a significant decrease of both crystallinity (-2 %)
      and mineral maturation (-41 %) in the BP-exposed bone sequesters compared to
      healthy bones. These modifications were also observed distinctly in both benign
      BP and malignant-BP groups. In addition, a shift of the phosphate nu1 band was
      highlighted by PLS-DA between bones control and BP-exposed bone sequesters,
      revealing a disruption of the apatitic phosphate environment in the jaw bone
      sequesters. CONCLUSIONS: The present data show that jaw bone quality can be
      altered with an overmineralization and ultrastructural modifications of apatitic
      mineral in bone sequesters of BP-related ONJ.

PMID- 24081511
TI  - Neglected patellar tendon ruptures: a simple modified reconstruction using
      hamstrings tendon graft.
AB  - PURPOSE: We hereby describe a cost effective and simple anatomical reconstruction
      without requirement for allograft or implants for neglected chronic patellar
      tendon injuries. This has been validated in seven patients with an average follow
      up of greater than three years resulting in good outcome. METHODS: Seven patients
      (six males, one female) of mean age 41.8 years (range up to 57 years) presented
      with neglected patellar tendon injury. The time since injury ranged between three
      months and three years (average nine months). Active extension was not possible
      in three patients, and four patients had an extensor lag between 40 degrees  and
      80 degrees  (average 62.5 degrees ). Four patients had quadriceps strength of
      grade 2/5 and three patients had grade 3/5. All patients had severe functional
      limitation with an average IKDC score of 46.8 (range 39-57). They all underwent
      patellar tendon reconstruction using hamstrings tendon autograft. RESULTS:
      Postoperatively with a mean follow up of 40.7 months (range 31-52 months), all
      patients had a stable knee with mean flexion of 125 degrees  (range 120 degrees 
      130 degrees ) and without any extension lag. Quadriceps power was regained in
      five cases to 5/5 and in two cases to 4/5. With an improvement in the IKDC score
      to 86.8 (range 80-92), excellent outcome was noted in five patients and good
      outcome in two patients. The average postoperative Lysholm score was 92.4 (range
      89-95) and the average Kujala score was 94.5 (range 92-97). CONCLUSION: Patellar
      tendon reconstruction using hamstrings autograft for neglected patellar tendon
      injuries provides good stability and excellent outcome. Compared to previous
      techniques described, our technique is unique in being cost effective and a
      simple anatomical reconstruction without the requirement for allograft or
      implants.

PMID- 24081512
TI  - Design of benzothiazole-1,3,4-thiadiazole conjugates: synthesis and
      anticonvulsant evaluation.
AB  - Various 2-[(6-substituted-1,3-benzothiazol-2-yl)amino]-N-[5-substituted-phenyl
      1,3,4-thiadiazol-2-yl]acetamides were synthesized with a prospective exploration
      of "lead hopping", using pharmacophoric elements for in vivo anticonvulsant
      activity. This yielded three potent candidates (5i, 5t, and 5u) in the
      preliminary screening employing the maximal electroshock seizure (MES) and the
      subcutaneous pentylenetetrazole (scPTZ) test, showing minimal neurotoxicity.
      Their quantitative study indicated an increase of nearly 2-10 times for the MES
      test and 7- to 67-fold for the scPTZ test in the protective index, the keystone
      in drug discovery for anticonvulsant activity. 

PMID- 24081514
TI  - [Participation and its measurement].

PMID- 24081513
TI  - Association of single-nucleotide polymorphisms in the STAT3 gene with autoimmune
      thyroid disease in Chinese individuals.
AB  - The aim of this study was to investigate the association between signal
      transducer and activator of transcription 3 (STAT3) polymorphisms and autoimmune
      thyroid diseases and clinical features. We genotyped six single-nucleotide
      polymorphisms (SNPs) rs1053005, rs2293152, rs744166, rs17593222, rs2291281, and
      rs2291282 of STAT3 gene in 667 patients with autoimmune thyroid disease (417
      Graves' disease (GD) and 250 Hashimoto's thyroiditis (HT)) and 301 healthy
      controls. The allele A from rs1053005 was significantly less frequent in both GD
      and HT patients (P = 0.0024, OR = 0.6958, 95%CI = 0.5508-0.8788; P = 0.0091, OR =
      0.7013, 95%CI = 0.5397-0.9112, respectively). The AA genotype of rs1053005 was
      less in GD and HT patients too (P = 0.0025,OR = 0.6278, 95%CI = 0.466-0.847) and
      (P = 0.0036,OR = 0.601, 95%CI = 0.428-0.843). The allele G from rs17593222
      increased the susceptibility to the ophthalmopathy development both in autoimmune
      thyroid disease (AITD) and GD patients (P = 0.0007, OR = 3.980, 95%CI = 1.871
      8.464; P = 0.0081, OR = 3.378, 95%CI = 1.441-7.919, respectively). The allele A
      and AA genotype of SNP rs1053005 may protect individuals from the susceptibility
      to AITD and their frequency decreased in AITD patients. In addition, the allele G
      of rs17593222 may increase the ophthalmopathy risk in AITD patients. Our findings
      suggest the existence of association between STAT3 gene and AITD, thus adding
      STAT3 gene to the list of the predisposing genes to AITD.

PMID- 24081515
TI  - [Repetitive transcranial magnetic stimulation (rTMS) for anxiety disorders--a
      possible therapeutic option?].
AB  - Anxiety disorders rank among the most frequent psychiatric disorders. Effective
      psychotherapeutic and psychopharmacological interventions exist, although a
      considerable number of patients does not respond to standard interventions.
      Repetitive transcranial magnetic stimulation (rTMS) is capable of modulating
      cortical activity locally and non-invasively. Therefore, rTMS is discussed as a
      possible alternative treatment approach in psychiatric disorders. The present
      paper aims to provide a systematic review of randomised controlled studies, open
      studies, and case reports examining the potential therapeutic effects of rTMS in
      anxiety disorders. Overall, these studies suggest beneficial effects of rTMS on
      anxiety symptoms. Nevertheless, larger randomised controlled studies are
      warranted to allow a more comprehensive evaluation of the therapeutic efficacy of
      rTMS in anxiety disorders. 

PMID- 24081516
TI  - [Sleep disturbances and suicidality: relationships and clinical implications].
AB  - Besides several risk factors for suicide, there is a recent increase in clinical
      and epidemiological studies pointing to a potential relationship between sleep
      loss or sleep disturbances and suicidality. This work, based on a systematic
      literature research, gives an overview on the findings of relationships between
      suicidality (i. e., suicidal thoughts, suicide attempts, suicides) and sleep
      disturbances, especially insomnia, nightmares, but also hypersomnia and nocturnal
      panic attacks. There is evidence that sleep disturbances in suicidal insomniacs
      with comorbid psychiatric disorder are independently predictive for suicidality,
      too. Shared aspects of pathogenesis of the two entities and therapeutic options
      are also discussed. Recognition of sleep disturbances is essential for suicide
      prevention in clinical practice. 

PMID- 24081517
TI  - [Measurement of participation in outpatient neurorehabilitation--a pilot study].
AB  - OBJECTIVE: To date there is a lack of tools to measure participation and the
      already existing measures are not properly used as yet. In 2005 the IMET (Index
      zur Messung von Einschrankungen der Teilhabe) was developed and is able to
      measure the ICF associated construct participation as a generic instrument in
      chronic diseases. IMET and numerous instruments were applied in our own study and
      results were compared with results of an unpublished study. In addition, to test
      IMET for its use in neurorehabilitation the effects of outpatient
      neurorehabilitation were investigated and compared with results obtained in an
      inpatient setting. METHOD: In a multicentric observational study, consecutively
      treated patients of 6 outpatient neurorehabilitation centres were asked to fill
      in a questionnaire at three time points (admission and discharge in the course of
      rehabilitation and at 4 months follow-up). Additionally, clinical experts were
      asked to rate the patients' status at admission and discharge. The data were
      compared with results of a sample of inpatients of an unpublished study. RESULTS:
      The IMET seems to be the to date best instrument to measure participation in a
      global, ICF-defined and economic way. Especially participation, general health
      status and capacity in leisure time and daily routine show the biggest
      improvements. In comparison, the outpatients show improvements in their
      participation status. Participation-oriented outpatient neurorehabilitation seems
      to have a considerable impact on participation status in neurological patients
      through the course of rehabilitation.

PMID- 24081518
TI  - [Thrombolysis for acute stroke--a nationwide analysis of regional medical care].
AB  - BACKGROUND: This study aims at investigating ischaemic stroke therapy in Germany
      by using secondary data. The focus lies on the performance of thrombolysis.
      METHODS: Statutory quality report data for 2010 were obtained. All hospitals (n =
      1302) treating patients suffering from an ischaemic stroke either on a
      neurological, internal, geriatric or intensive care unit were analysed. The
      treatment situation, defined as the experience in performing thrombolysis, was
      displayed cartographically. Potential variables that may influence the
      thrombolysis rate were analysed. RESULTS: 78 % of the 198,500 ischaemic stroke
      cases were treated on a ward specialised in the stroke treatment (i. e., a stroke
      unit). The mean thrombolysis rate in neurological departments was 9.1 %.
      Thrombolysis rates between departments ranged from 0 to 38 %. Significant factors
      influencing the thrombolysis rate were the total number of ischaemic strokes
      treated as well as the existence of a stroke unit. DISCUSSION: In Germany, to
      date regional differences in the treatment of ischaemic stroke exist. Experience
      in the treatment of ischaemic stroke patients and the availability of a stroke
      unit both increase the thrombolysis rate. Data suggest that in Germany there is
      still room for improvement of appropriate ischaemic stroke treatment.

PMID- 24081519
TI  - [Adolf Abraham Gustav Bingel (1901-1982): pioneer of electroconvulsive treatment
      in Germany].
AB  - INTRODUCTION: Adolf Bingel, internal medicine specialist, neurologist and
      psychiatrist, was a pioneer in the establishment of electroconvulsive treatment
      (ECT) in Germany. Thanks to his dedication, the psychiatric department of the
      University of Erlangen was Germany's first clinic to offer ECT. METHODS: We have
      analysed relevant archival material and the secondary literature. RESULTS: As a
      consequence of denazification, Adolf Bingel was classified as a hanger-on by the
      Tribunal in Heidelberg. In 1946 the accredited German scientist moved to Houston
      as a "Paperclip-Boy". DISCUSSION: The ECT-pioneer Bingel has repeatedly been
      mistaken for the co-inventor of pneumo-encephalograpy, whose name was also Adolf
      Bingel. This confusion in names has to be corrected. CONCLUSION: In 1957 Bingel
      was awarded the title Associate Professor Emeritus by the University of Erlangen.
      In 1959 he became Associate Professor of Neurology/Baylor University College in
      Houston/Texas.

PMID- 24081520
TI  - [Diagnostics and therapy for amyotrophic lateral sclerosis].

PMID- 24081521
TI  - Alda-1 reduces cerebral ischemia/reperfusion injury in rat through clearance of
      reactive aldehydes.
AB  - Many studies demonstrate that accumulation of reactive aldehydes plays an
      important role in cellular oxidative injury and aldehyde dehydrogenase 2 (ALDH2)
      mediated detoxification of reactive aldehydes is thought as an endogenous
      protective mechanism against cell injury. This study was performed to explore
      whether Alda-1, a newly identified ALDH2 activator, was able to protect brain
      against ischemia/reperfusion injury through clearance of reactive aldehydes. In a
      rat model of focal cerebral ischemia/reperfusion injury, neurological function,
      infarct volume, cellular apoptosis, mortality, ALDH2 activity and protein
      expression, contents of 4-hydroxy-2-nonenal (4-HNE), and malondialdehyde (MDA)
      were determined. The results showed that ischemia/reperfusion treatment led to
      increase in neurological deficit score, infarct volume, cellular apoptosis, and
      mortality accompanied by the elevated levels of reactive aldehydes (4-HNE and
      MDA). There was no significant change in ALDH2 activity and protein expression.
      Alda-1 treatment at both dosages (15 mg/kg * 2 or 50 mg/kg * 2, i.g.) was able to
      increase the activity of ALDH2 and decrease the accumulation of reactive
      aldehydes concomitantly with the improvement of brain injury (decrease in infarct
      volume, cellular apoptosis, and mortality) and neurological function (decrease in
      neurological deficit score). However, Alda-1 treatment did not affect ALDH2
      protein expression. Our results suggest that the protective effect of Alda-1 on
      cerebral ischemia/reperfusion injury is related to ALDH2 activation and clearance
      of reactive aldehydes. 

PMID- 24081522
TI  - Extracellular loop 3 of the noradrenaline transporter contributes to substrate
      and inhibitor selectivity.
AB  - The human noradrenaline transporter (NET) and 5-hydroxytryptamine (5-HT)
      transporter (SERT) are inhibited by antidepressants and psychoactive drugs such
      as cocaine. Both substrates and inhibitors bind in the transmembrane core of the
      protein, but molecular divergence at the binding site is not sufficient to
      account for the NET-selective and SERT-selective inhibition of the
      antidepressants, desipramine and citalopram, respectively. We considered that the
      poorly conserved third extracellular loop may contribute to these differences. We
      substituted single amino acid residues of the third extracellular loop in NET for
      equivalents from SERT, transiently transfected COS-7 cells with WT NET, 13 mutant
      NETs and WT SERT, and measured [(3)H]noradrenaline uptake, [(3)H]nisoxetine
      binding and [(3)H]5-HT uptake. Mutants F299W, Y300Q, R301K and K303L, at the C
      terminal end of EL3, all showed significantly decreased [(3)H]nisoxetine binding,
      indicative of a reduced cell surface expression. Most mutants differed little, if
      at all, from WT NET regarding [(3)H]noradrenaline uptake; however, the I297P
      mutant showed no significant uptake activity despite intact cell surface
      expression, and the A293F mutant showed a significantly slower transporter
      turnover than WT NET in addition to [(3)H]5-HT uptake that was significantly
      greater than that of WT NET. The A293F mutation also decreased desipramine
      potency and increased the inhibition of [(3)H]noradrenaline uptake by citalopram
      compared to WT NET. These results suggest that the third extracellular loop
      allosterically regulates the ability of the transmembrane domains to transport
      substrates and bind inhibitors and thus contributes to the selectivity of
      substrates and antidepressants for NET and SERT. 

PMID- 24081523
TI  - Microfilarial periodicity of Dirofilaria repens in naturally infested dogs.
AB  - In the past years, canine and human cases of infestation by Dirofilaria repens
      (Spirurida, Onchocercidae) have been increasingly reported in several European
      countries. Subcutaneous dirofilariosis by D. repens may either be asymptomatic in
      dogs or may be characterized by subcutaneous nodules and other symptoms.
      Information on the periodicity of D. repens microfilariae in naturally infested
      animals is scant, and this might impair the accurate diagnosis of subcutaneous
      dirofilariosis and appropriate control plans. In the present study, eight dogs
      infested with D. repens were sampled twice daily at 12-h intervals for ten
      consecutive days, and the dog with the highest mean value of microfilariaemia was
      further sampled every 4 h for four consecutive days. The blood was
      microscopically and molecularly examined for microfilariae, and, additionally,
      negative samples were also subjected to a real-time PCR to evaluate the level of
      circulating DNA. The results demonstrated significant variations in circadian
      rhythms of D. repens larvae, with higher values of microfilariae per milliliter
      in the evening samples. A significant variation was also found at the individual
      level for the dogs with the highest values of microfilariaemia. All samples which
      were negative at the light microscopy and positive at the real-time PCR displayed
      levels of circulating parasite DNA <1 microfilaria per milliliter. Biological and
      clinical implications have been here discussed. 

PMID- 24081525
TI  - Theodore John Leppi (1933-2010).

PMID- 24081526
TI  - 2,6-dansyl azide as a fluorescent probe for hydrogen sulfide.
AB  - A second-generation sulfonyl azide-based fluorescent probe, 2,6-DNS-Az, has been
      developed for the quantitative detection of H2S in aqueous media such as
      phosphate buffer and bovine serum. Compare to the first-generation 1,5-DNS-Az
      probe, this probe shows both high sensitivity in phosphate buffer without the
      need for addition of surfactant and selectivity for sulfide over other anions and
      biomolecules, and thus can be used as a useful tool for detection of H2S in the
      biological system. 

PMID- 24081524
TI  - Effect of AMPK activation on monocarboxylate transporter (MCT)1 and MCT4 in
      denervated muscle.
AB  - It is now evident that exercise training leads to increases in monocarboxylate
      transporter (MCT)1 and MCT4, but little is known about the mechanisms of coupling
      muscle contraction with these changes. The aim of this study was to investigate
      the effect of 5-aminoimidazole-4-carboxamide-1-beta-D-ribofuranoside (AICAR)
      induced activation of AMP-activated protein kinase (AMPK) on MCT1, MCT4, and
      GLUT4 in denervated muscle. Protein levels of MCT4 and GLUT4 after 10 days of
      denervation were significantly decreased in mice gastrocnemius muscle, while MCT1
      protein levels were not altered. AICAR treatment for 10 days significantly
      increased MCT4, and GLUT4 protein levels in innervated muscle as shown in
      previous studies. We found that the MCT1 protein level was also increased in
      AICAR treated innervated muscle. AICAR treatment prevented the decline in MCT4
      and GLUT4 protein levels in denervated muscle. Thus, the current study suggests
      that MCT1 and MCT4 protein expression in muscles, as well as GLUT4, may be
      regulated by AMPK-mediated signal pathways, and AMPK activation can prevent
      denervation-induced decline in MCT4 protein. 

PMID- 24081527
TI  - Clinical significance of ghrelin expression in the gastric mucosa of morbidly
      obese patients.
AB  - BACKGROUND: The concentration of ghrelin, which can affect body weight by
      influencing appetite, is thought to decrease after sleeve gastrectomy. However,
      no detailed investigations have examined ghrelin expression in the stomach. The
      purpose of the present study was to assess localized ghrelin expression and its
      clinical significance in obese patients. METHODS: A total of 52 obese patients
      who underwent sleeve gastrectomy with or without duodenojejunal bypass were
      enrolled in the study. The number of ghrelin-positive cells (GPCs) was counted
      using immunohistochemistry of the gastric mucosa at the fundus. The obese
      patients were compared with 14 nonobese patients treated for gastric cancer.
      Ghrelin mRNA expression was also measured in 22 obese patients using a
      quantitative reverse transcription polymerase chain reaction. RESULTS: The number
      of GPCs was significantly higher in obese patients than in nonobese controls
      (33.2 +/- 18.3 vs. 14.1 +/- 6.1; p < 0.001) and correlated with ghrelin mRNA
      expression. The obese patients were divided into two groups with high and low
      ghrelin levels based on the number of GPCs. The percent excess body weight loss
      was significantly greater in the high-ghrelin group, without differences in the
      patient backgrounds between the two groups (p = 0.015). CONCLUSIONS: The number
      of GPCs was higher in obese patients than in nonobese patients and varied
      individually regardless of body weight. These results suggest that ghrelin
      expression in gastric mucosa might be a prognostic factor after surgery.

PMID- 24081528
TI  - Surgical outcomes of gastrectomy for elderly patients with gastric cancer.
AB  - BACKGROUND: This study was designed to determine the surgical outcomes of gastric
      cancer in elderly patients. This information can help establish appropriate
      treatment for these patients. METHODS: A total of 1,193 patients with gastric
      cancer who underwent gastrectomy between 1995 and 2010 were enrolled in this
      retrospective study. The clinicopathologic features of 104 elderly patients (aged
      >=80 years) were compared with those of 1,089 nonelderly patients. RESULTS: (1)
      Tumors located in the lower-third of the stomach, differentiated cancer, and
      surgery with limited lymph node dissection were more common in elderly patients.
      However, there was no difference in the proportion of laparoscopic gastrectomy
      between elderly and nonelderly patients. (2) Although surgical complication rates
      were similar in the two groups, the operative mortality rate was higher in
      elderly patients (1.9 %) than in nonelderly patients (0.7 %). (3) Elderly
      patients had a significantly poorer overall survival rate, whereas the disease
      specific survival rates of the two groups were similar. Limited lymph node
      dissection did not influence the disease-specific survival rate of elderly
      patients. (4) The median life expectancy of elderly gastric cancer survivors was
      9.8 years in patients aged 80-84 years and 6.0 years in those >=85 years. The
      patients with limited lymph node dissection had slightly better prognosis.
      CONCLUSIONS: The treatment results in elderly patients were comparable to those
      in nonelderly patients. These findings suggest that R0 resection with at least
      limited lymph node dissection according to Japanese guidelines should be
      considered, even for elderly patients.

PMID- 24081529
TI  - Outcomes of chemical component paralysis using botulinum toxin for incisional
      hernia repairs.
AB  - BACKGROUND: Botulinum toxin A (BTX) confers flaccid paralysis and pain modulation
      when injected into a muscle. We hypothesized that long-term paralysis of the
      abdominal wall musculature (i.e., chemical component paralysis, CCP) would
      benefit incisional hernia repair (IHR) by decreasing postoperative pain, the use
      of opioid analgesia, and thus opioid-related side effects. METHODS: Adult
      patients who underwent elective IHR with preoperative CCP (n = 22) were compared
      to concurrent matched controls (n = 66, 1:3 ratio) based on age (+/-5 years),
      sex, body mass index (+/-5 kg/m(2)), history of hernia recurrence (0 vs. >=1),
      and type of repair (open vs. laparoscopic). BTX was injected under
      ultrasonographic guidance into the transversus abdominis and internal and
      external oblique muscles at three sites bilaterally (300 units total). RESULTS:
      Patients who underwent IHR with CCP used significantly less opioid analgesia
      (mean +/- SD morphine equivalents) when compared to controls on hospital days
      (HDs) 2 and 5: HD2, 48 +/- 27 versus 87 +/- 41; HD5, 17 +/- 16 versus 48 +/- 45.
      Likewise, CCP patients reported significantly less pain (visual analogue scale 1
      10) when compared to controls on HD2 (5.2 +/- 1.5 vs. 6.8 +/- 2) and HD4 (3.6 +/-
      1.2 vs. 5.2 +/- 1.9): all p < 0.007 (Bonferroni adjusted). There was no
      difference in postoperative complications (surgical site, 9 vs. 14 %), opioid
      related adverse events (ileus 5 vs. 5 %), hospital stay (4 +/- 3 vs. 3 +/- 2
      days), or hernia recurrence (18 months mean follow-up: 9 vs. 9 %). CONCLUSIONS:
      Despite similar multimodality treatment of postoperative pain after IHR, patients
      who underwent CCP required significantly less opioid analgesia and reported less
      pain.

PMID- 24081530
TI  - Outcomes of chemical component paralysis using botulinum toxin for incisional
      hernia repairs.

PMID- 24081531
TI  - Single-incision and NOTES cholecystectomy, are there clinical or cosmetic
      advantages when compared to conventional laparoscopic cholecystectomy? A case
      control study comparing single-incision, transvaginal, and conventional
      laparoscopic technique for cholecystectomy.
AB  - BACKGROUND: The aim of the present study was to compare the clinical and cosmetic
      results of transvaginal hybrid cholecystectomy (TVC), single-port cholecystectomy
      (SPC), and conventional laparoscopic cholecystectomy (CLC). Recently, single
      incision laparoscopic surgery and natural orifice transluminal endoscopic surgery
      have been developed as minimally invasive alternatives for CLC. Few comparative
      studies have been reported. METHODS: Female patients with symptomatic gallstone
      disease who were treated in 2011 with SPC, TVC, or CLC were entered into a
      database. Patients were matched for age, body mass index, and previous abdominal
      surgery. After the operation all patients received a survey with questions about
      recovery, cosmesis, and body image. RESULTS: A total of 90 patients, 30 in each
      group, were evaluated. Median operative time for CLC was significantly shorter (p
      < 0.001). There were no major complications. Length of hospital stay,
      postoperative pain, and postoperative complications were not significantly
      different. The results for cosmesis and body image after the transvaginal
      approach were significantly higher. None of the sexually active women observed
      postoperative dyspareunia. CONCLUSIONS: Both SPC and TVC are feasible procedures
      when performed in selected patients. CLC is a faster procedure, but other
      clinical outcomes and complication rates were similar. SPC, and especially TVC,
      offer a better cosmetic result. Randomized trials are needed to specify the role
      of SPC and TVC in the treatment of patients with symptomatic gallstone disease.

PMID- 24081532
TI  - Thyroid lobectomy for papillary thyroid cancer: long-term follow-up study of
      1,088 cases.
AB  - BACKGROUND: Total thyroidectomy is well accepted as initial surgery for papillary
      thyroid cancer (PTC), but the extent of the thyroidectomy remains a matter of
      controversy. This study was designed to investigate the long-term clinical
      outcome of PTC patients who had undergone thyroid lobectomy and to elucidate the
      indications of lobectomy as initial surgery. METHODS: The cases of 1,088 PTC
      patients who underwent thyroid lobectomy with curative intent at Ito Hospital
      between 1986 and 1995 were analyzed retrospectively in this study. None of the
      patients had received postoperative radioactive iodine (RAI) ablation therapy.
      The median follow-up period was 17.6 years. All clinical outcomes, including
      recurrence and death as a result of PTC or other reasons, were evaluated. To
      establish the indications for lobectomy as initial surgery for PTC, the potential
      risk factors, such as age, sex, primary tumor size, extrathyroidal invasion, and
      clinical lymph node metastasis at the time of the initial surgery, were assessed
      statistically for associations with recurrence and disease-related death.
      RESULTS: The remnant-thyroid recurrence-free survival (RT-RFS) rate, the regional
      lymph-node recurrence-free survival (L-RFS) rate, and the distant-recurrence
      free survival (D-RFS) rate as of 25 years after surgery were 93.5, 90.6, and
      93.6%, respectively. The cause-specific survival (CSS) rate at 25 years was
      95.2%. Univariate and multivariate analyses showed that none of the factors
      assessed were significantly associated with the RT-RFS rate. Tumor size, clinical
      lymph node metastasis, and extrathyroidal invasion were significantly associated
      with the L-RFS rate. The D-RFS and CSS rates were both significantly lower in the
      group of patients who were aged 45 years old or older, the group whose tumors
      were larger than 40 mm, and the group with extrathyroidal invasion. Based on the
      above findings, we classified the patients into four groups according to age <45
      or >= 45 years, tumor size <= 40 or >40 mm, whether clinical lymph node
      metastasis was present, and whether extrathyroidal invasion was present. None of
      the patients without any of these four risk factors died of PTC. On the other
      hand, 22 patients who died of PTC were positive for one or more of these four
      factors. CONCLUSIONS: The long-term clinical outcome of the PTC patients who had
      been treated by lobectomy without RAI ablation was excellent. Based on the above
      results, we concluded that lobectomy is a valid alternative to total
      thyroidectomy for the treatment of PTC patients who are younger than aged 45
      years, whose tumor diameter is 40 mm or less, and who do not have clinical lymph
      node metastasis or extrathyroidal invasion.

PMID- 24081533
TI  - A prospective evaluation of missed injuries in trauma patients, before and after
      formalising the trauma tertiary survey.
AB  - OBJECTIVE: This study prospectively evaluated in-hospital and postdischarge
      missed injury rates in admitted trauma patients, before and after the
      formalisation of a trauma tertiary survey (TTS) procedure. METHODS: Prospective
      before-and-after cohort study. TTS were formalised in a single regional level II
      trauma hospital in November 2009. All multitrauma patients admitted between March
      October 2009 (preformalisation of TTS) and December 2009-September 2010 (post-)
      were assessed for missed injury, classified into three types: Type I, in
      hospital, (injury missed at initial assessment, detected within 24 h); Type II,
      in-hospital (detected in hospital after 24 h, missed at initial assessment and by
      TTS); Type III, postdischarge (detected after hospital discharge). Secondary
      outcome measures included TTS performance rates and functional outcomes at 1 and
      6 months. RESULTS: A total of 487 trauma patients were included (pre-: n = 235;
      post-: n = 252). In-hospital missed injury rate (Types I and II combined) was
      similar for both groups (3.8 vs. 4.8 %, P = 0.61), as were postdischarge missed
      injury rates (Type III) at 1 month (13.7 vs. 11.5 %, P = 0.43), and 6 months (3.8
      vs. 3.3 %, P = 0.84) after discharge. TTS performance was substantially higher in
      the post-group (27 vs. 42 %, P < 0.001). Functional outcomes for both cohorts
      were similar at 1 and 6 months follow-up. CONCLUSIONS: This is the first study to
      evaluate missed injury rates after hospital discharge and demonstrated cumulative
      missed injury rates >15 %. Some of these injuries were clinically relevant.
      Although TTS performance was significantly improved by formalising the process
      (from 27 to 42 %), this did not decrease missed injury rates.

PMID- 24081534
TI  - The use of short segment free jejunal transfer as salvage surgery for cervical
      esophageal and hypopharyngeal cancer.
AB  - BACKGROUND: Salvage surgery after definitive chemoradiotherapy for cervical
      esophageal cancer and hypopharyngeal cancer remains a challenge because of the
      high rate of complications. The purpose of this study was to evaluate the safety
      and efficacy of free jejunal transfer as salvage surgery for cervical esophageal
      cancer and hypopharyngeal cancer after definitive chemoradiotherapy. METHODS: We
      enrolled eight patients with cervical esophageal cancer and 11 patients with
      hypopharyngeal cancer who underwent free jejunal transfer as salvage surgery
      following radiotherapy or chemoradiotherapy. In this study, we reviewed the
      surgical procedures, perioperative complications, and survival rates. RESULTS:
      The median duration of surgery was 514 min, and the median blood loss was 439 ml.
      In surgical procedures, the recipient vessels for the anastomosis of the free
      jejunum consisted of one artery and one vein (63 %), one artery and two veins (5
      %), and two arteries and two veins (31 %). The postoperative morbidity rate was
      57.9 % (11 patients), with six cases of partial necrosis of the tracheal margin
      and no cases of graft necrosis or postoperative in-hospital death. The overall 5
      year survival rate after surgery was 58.1 %. CONCLUSIONS: Our findings suggest
      that with careful attention to the potential development of necrosis of the
      tracheal margin, pharyngolaryngoesophagectomy and free jejunal transfer can be
      safely performed, even in patients who received radiotherapy or
      chemoradiotherapy.

PMID- 24081535
TI  - Trends in use of upper abdominal procedures in Sweden 1998-2011: a population
      based study.
AB  - BACKGROUND: Surgical care is constantly developing as demographic shifts occur
      and indications change when new techniques are introduced. The purpose of this
      study was to describe trends of in-hospital upper abdominal procedures in Sweden
      during 1998-2011. METHODS: Data were collected from the National Patient Register
      containing annual number of procedures and procedures per 100,000 inhabitants.
      Comparisons were made between the first 3 years (1998-2000) and last 3 years
      (2009-2011). High-volume procedures and resectional surgery were studied in
      particular. RESULTS: During the study period, a total of 435,394 upper abdominal
      procedures were performed in 318,991 individuals. The number of procedures
      increased 44.9 % between the early and late period. Bariatric surgery increased
      almost sixfold, with a substantial increase in laparoscopic gastric bypass to
      58.2/100,000/year. The most common operation was cholecystectomy,
      144.9/100,000/year. Liver resections tripled and, in total, major resectional
      surgery, performed on the esophagus, stomach, liver, and pancreas, increased by
      36.3 %. Per 100,000 adult inhabitants and year, resections of the esophagus was
      performed in 2.3 patients, stomach in 5.9, liver in 9.0, and pancreas in 5.7, in
      late time period. An increase in all types of endoscopic work was observed.
      CONCLUSIONS: In total, the number of upper abdominal procedures performed per
      inhabitant increased. Laparoscopic gastric bypass increased substantially and
      became the second most common procedure after laparoscopic cholecystectomy. An
      increase in resectional surgery was observed.

PMID- 24081536
TI  - York Mason procedure to repair iatrogenic rectourinary fistula.

PMID- 24081537
TI  - Inferior right hepatic vein-preserving major right hepatectomy for hepatocellular
      carcinoma in patients with significant fibrosis or cirrhosis.
AB  - BACKGROUND: Liver resection represents a most effective treatment for
      hepatocellular carcinoma (HCC). The extent of hepatectomy for HCC involves
      maintaining a tricky balance between radical resection of tumors and preservation
      of sufficient liver parenchyma. Generally, removal of the right hepatic vein
      often involves resection of the whole posterior right lobe, which may prevent
      patients with impaired liver function from maintaining a functional reserve and
      could also limit the future liver remnant from curative hepatectomy. As a common
      anatomic variation, preservation of the inferior right hepatic vein (IRHV) may
      enable preservation of liver segment 6, even when the right hepatic vein has to
      be removed. In the present study, we report our experience with IRHV-preserving
      major right hepatectomy. METHODS: From February 2009 to December 2011, eight
      trisegmentectomies 5-7-8 and two segmentectomies 4-5-7-8 were performed with the
      IRHV-sparing technique on patients with HCC and significant fibrosis or
      cirrhosis. Data including demographic information, preoperative evaluations,
      postoperative outcomes, and follow-up results were collected and evaluated.
      RESULTS: All patients survived and recovered from hepatectomy. The incidence of
      complications was higher in cirrhotic patients. The 1-year overall survival rate
      was 80 %, and the 1-year disease free survival rate was 60 %. CONCLUSIONS: IRHV
      preserving major right hepatectomy increases the resectability of HCC.
      Intraoperative ultrasonography is recommended to facilitate protection of the
      IRHV. This technique is safe with careful preoperative evaluation and meticulous
      perioperative care. The short-term outcome of IRHV-preserving liver resections is
      satisfactory.

PMID- 24081538
TI  - Intraoperative nerve monitoring can reduce prevalence of recurrent laryngeal
      nerve injury in thyroid reoperations: results of a retrospective cohort study.
AB  - BACKGROUND: The prevalence of recurrent laryngeal nerve (RLN) injury is higher in
      repeat than in primary thyroid operations. The use of intraoperative nerve
      monitoring (IONM) as an aid in dissection of the scar tissue is believed to
      minimize the risk of nerve injury. The aim of this study was to examine whether
      the use of IONM in thyroid reoperations can reduce the prevalence of RLN injury.
      METHODS: This was a retrospective cohort study of patients who underwent thyroid
      reoperations with IONM versus with RLN visualization, but without IONM. The
      database of thyroid surgery was searched for eligible patients (treated in the
      years 1993-2012). The primary outcomes were transient and permanent RLN injury.
      Laryngoscopy was used to evaluate and follow RLN injury. RESULTS: The study group
      comprised 854 patients (139 men, 715 women) operated for recurrent goiter (n =
      576), recurrent hyperthyroidism (n = 36), completion thyroidectomy for cancer (n
      = 194) or recurrent thyroid cancer (n = 48), including 472 bilateral and 382
      unilateral reoperations; 1,326 nerves at risk (NAR). A group of 306 patients (500
      NAR) underwent reoperations with IONM and 548 patients (826 NAR) had reoperations
      with RLN visualization, but without IONM. Transient and permanent RLN injuries
      were found respectively in 13 (2.6 %) and seven (1.4 %) nerves with IONM versus
      52 (6.3 %) and 20 (2.4 %) nerves without IONM (p = 0.003 and p = 0.202,
      respectively). CONCLUSIONS: IONM decreased the incidence of transient RLN paresis
      in repeat thyroid operations compared with nerve visualization alone. The
      prevalence of permanent RLN injury tended to be lower in thyroid reoperations
      with IONM, but statistical validation of the observed differences requires a
      sample size of 920 NAR per arm.

PMID- 24081540
TI  - The prognostic relevance of psammoma bodies and ultrasonographic intratumoral
      calcifications in papillary thyroid carcinoma: reply.

PMID- 24081539
TI  - Thyroid nodules (>=4 cm): can ultrasound and cytology reliably exclude cancer?
AB  - BACKGROUND: Whether a threshold nodule size should prompt diagnostic
      thyroidectomy remains controversial. We examined a consecutive series of patients
      who all had thyroidectomy for a >=4 cm nodule to determine (1) the incidence of
      thyroid cancer (TC) and (2) if malignant nodules could accurately be diagnosed
      preoperatively by ultrasound (US), fine needle aspiration biopsy (FNAB) cytology
      and molecular testing. METHODS: As a prospective management strategy, 361
      patients with 382 nodules >=4 cm by preoperative US had thyroidectomy from 1/07
      to 3/12. RESULTS: The incidence of a clinically significant TC within the >=4 cm
      nodule was 22 % (83/382 nodules). The presence of suspicious US features did not
      discriminate malignant from benign nodules. Moreover, in 86 nodules >=4 cm with
      no suspicious US features, the risk of TC within the nodule was 20 %. US-guided
      FNAB was performed for 290 nodules, and the risk of malignancy increased stepwise
      from 10.4 % for cytologically benign nodules, 29.6 % for cytologically
      indeterminate nodules and 100 % for malignant FNAB results. Molecular testing was
      positive in 9.3 % (10/107) of tested FNAB specimens, and all ten were histologic
      TC. CONCLUSIONS: In a large consecutive series in which all >=4 cm nodules had
      histology and were systematically evaluated by preoperative US and US-guided
      FNAB, the incidence of TC within the nodule was 22 %. The false negative rate of
      benign cytology was 10.4 %, and the absence of suspicious US features did not
      reliably exclude malignancy. At minimum, thyroid lobectomy should be strongly
      considered for all nodules >=4 cm.

PMID- 24081541
TI  - Catheter-based endovascular damage-control (CDET): current status and future
      directions.
AB  - INTRODUCTION: Endovascular technology during the past decade has introduced
      innovative strategies to manage vascular trauma. The purpose of this study was to
      evaluate the current use catheter-based endovascular damage-control techniques
      (CDET) in North, Central, and South America. METHODS: A survey was sent to the
      presidents of local societies in Latin America, members of the board, and past
      presidents of the Pan-American Trauma Society. The survey was sent using the
      Research Electronic Data Capture collection tool. RESULTS: A total of 67 surveys
      were sent with an 85 % response rate. Surgeons from 15 countries participated in
      the survey. All of the centers in North America had capabilities to perform these
      procedures. In none of these centers, however, were they performed by trauma and
      acute care surgeons. In Central and South America, 64 % of the surgeons responded
      that they have an interventional radiology service, and in 56 % of the cases,
      trauma and acute care surgeons were already performing CDET. Eight-eight percent
      of those surveyed thought that the addition of CDET to trauma would improve
      patient care; 86 % would be interested in further training in this technique if
      such programs were available. Finally, 68 % thought that the addition of CDET
      would help the field of acute care surgery and trauma financially. CONCLUSIONS:
      CDET is being performed already by trauma and acute care surgeons in Latin
      American countries. More research is necessary to evaluate the role of the trauma
      surgeon in the endovascular suite as well as training requirements.

PMID- 24081542
TI  - Open versus thoracoscopic esophagectomy in patients with esophageal squamous cell
      carcinoma.
AB  - BACKGROUND: The impact of minimally invasive esophagectomy on patient prognosis,
      particularly disease-free survival (DFS), has not been well addressed. We
      compared the clinical outcomes of open and thoracoscopic esophagectomy in
      patients with esophageal squamous cell carcinoma (ESCC). METHODS: Sixty-three and
      66 patients, nonrandomized, underwent open and thoracoscopic esophagectomies for
      ESCC between 2008 and 2011 were included. The clinicopathological data were
      reviewed retrospectively. Perioperative outcome, overall survival (OS), DFS, and
      the recurrence sites after open and thoracoscopic esophagectomy were compared.
      RESULTS: The open and thoracoscopic groups were comparable with regard to the
      total number of harvested lymph nodes and the percentage patients undergoing R0
      resection. Fewer patients in the thoracoscopic group had pneumonia and wound
      complications. Intensive care unit (ICU) stay also was shorter in the
      thoracoscopic group. The recurrence pattern was similar in the two groups. In the
      open and thoracoscopic groups, the 3-year OS rates were 47.6 and 70.9 % (p =
      0.031), respectively, and the 3-year DFS rates were 35 and 62.4 % (p = 0.007),
      respectively. However, the trends in better OS and DFS in the thoracoscopic group
      were not significant after stratification according to pathologic stage.
      CONCLUSIONS: The perioperative benefit of thoracoscopic esophagectomy included
      fewer postoperative complications and shorter ICU stays. Mid-term OS and DFS
      associated with thoracoscopic techniques are at least equivalent to those
      associated with open procedures.

PMID- 24081543
TI  - Oncological feasibility of laparoscopic distal pancreatectomy for adenocarcinoma:
      a single-institution comparative study.
AB  - BACKGROUND: Laparoscopic distal pancreatectomy (LDP) is performed increasingly
      for pancreatic pathology in the body and tail of the pancreas. However, only few
      reports have compared its oncological efficacy with open distal pancreatectomy
      (ODP). We compared these two techniques in patients with pancreatic ductal
      adenocarcinoma. METHODS: From a prospectively maintained database, all patients
      who underwent either LDP or ODP for adenocarcinoma in the body and tail of the
      pancreas between January 2008 and December 2011 were compared. Data were analysed
      using SPSS((r)) v19 utilising standard tests. A p value <0.05 was considered
      significant. RESULTS: Of 101 patients who underwent distal pancreatectomy, 22 had
      histologically confirmed adenocarcinoma (LDP n = 8, ODP n = 14). Both groups were
      well matched for age and the size of tumour (22 vs. 32 mm, p = 0.22).
      Intraoperative blood loss was 306 ml compared with 650 ml for ODP (p = 0.152). A
      longer operative time was noted for LDP (376 vs. 274 min, p < 0.05). Total length
      of stay was shorter for LDP compared with ODP (8 vs. 12 days, p = 0.05). The
      number of postoperative pancreatic fistulas were similar (LDP n = 2 vs. ODP n =
      3, p = 0.5). Complete resection (R0) was achieved in 88 % of LDP (n = 7) compared
      with 86 % of ODP (n = 12). The median number of lymph nodes harvested was 16 for
      LDP versus 14 for ODP. Overall 3-year survival also was similar: LDP = 82 %, ODP
      = 74 % (p = 0.89). CONCLUSIONS: From an oncological perspective, LDP is a viable
      procedure and its results are comparable to ODP for ductal adenocarcinomas
      arising in the body and tail of the pancreas.

PMID- 24081544
TI  - Understanding and supporting the resilience of a new generation of combat-exposed
      military families and their children.
AB  - Taking our nation to war has exposed a generation of military families and
      children to combat and its consequences. Every dollar spent on bullets, trucks,
      fuel, and food carried a future 'tax' in the form of consequences for
      psychological and physical health and family relationships. In this commentary, I
      focus on several themes that emerge from the special collection or articles. For
      example, I consider how best to define the ecological niche(s) occupied by
      military-connected children and families. Not surprisingly given significant gaps
      in our knowledge, evidence regarding the well-being of military-connected
      children is mixed. I also consider the multi-layered environments within which
      individuals and families function, recognizing both the challenges and
      opportunities they provide. The need to respond rapidly to the evolving needs of
      military families has highlighted the value of both prevention science and
      implementation science. Public health models emphasizing a full continuum of care
      that emphasizes not only treatment but also universal, selective, and indicated
      prevention also are appealing given the uneven density, uncertain locations, and
      unknown identities of military families in civilian communities (Beardslee 2013;
      Murphy and Fairbank 2013). Finally, it is important to recognize that we are at
      the beginning, not the end, of the post-war lifetimes for the new generation of
      veterans and their families. 

PMID- 24081545
TI  - Laparoscopic extralevator abdominoperineal excision of the rectum: short-term
      outcomes of a prospective case series.
AB  - BACKGROUND: Laparoscopic approaches for the resection of low rectal cancer and
      the extralevator technique for abdominoperineal excision are both becoming
      increasingly popular. There are little published data regarding the combined
      application of these techniques to the resection of low rectal tumours. The aim
      of this study was to assess the feasibility of such an approach and to appraise
      short-term outcomes in a consecutive series of patients undergoing laparoscopic
      extralevator abdominoperineal excision (ELAPE). METHODS: Consecutive patients
      undergoing laparoscopic ELAPE at our institution between 2008 and 2011 were
      identified from a prospectively maintained database. The abdominal phase of the
      operation was performed laparoscopically, and following extralevator resection,
      the perineum was reconstructed using a biologic mesh. All patients were enrolled
      in an enhanced recovery programme. RESULTS: Of 166 patients undergoing radical
      resection of rectal cancer at our institution between 2008 and 2011, 28 underwent
      laparoscopic ELAPE. Median age was 70 years, median body mass index was 27.5
      kg/m(2), and 71% were male. The conversion rate to laparotomy was 18%. Three
      patients (10.8%) had circumferential resection margins <1 mm; no intraoperative
      tumour perforation occurred. The median length of stay was 7 days, with a 30-day
      readmission rate of 21% and no 30-day mortality. Post-operative perineal wound
      complications occurred in 25%. At median 38-month follow-up (range 23-66 months),
      overall survival was 75%, disease-free survival was 71%, and there were three
      local recurrences (11%). CONCLUSIONS: Laparoscopic extralevator abdominoperineal
      excision can be safely performed without compromising short-term outcomes.

PMID- 24081546
TI  - Three cases of small bowel obstruction after laparoscopic ventral rectopexy using
      the V-Loc((r)) suture.

PMID- 24081547
TI  - The evidence base for rectal prolapse surgery: is resection rectopexy worth the
      risk?

PMID- 24081548
TI  - Usefulness of 3D transperineal ultrasound in severe stenosis of the anal canal:
      preliminary experience in four cases.
AB  - BACKGROUND: Organic or functional anal canal stenoses are uncommon conditions
      that occur in the majority of cases as a consequence of anal diseases. A proper
      assessment is fundamental for decision making; however, proctological examination
      and endoanal ultrasound are often unfeasible or very difficult to perform even
      under local or general anesthesia. We therefore began to use 3D transperineal
      ultrasound to assess patients. The aim of this study was to compare the results
      of evacuation proctography and 3D transperineal ultrasound in patients with
      severe anal canal stenosis. METHODS: Four consecutive patients with high-grade
      anal canal stenosis were evaluated using both proctography and 3D transperineal
      ultrasound with a micro-convex transducer between March and June 2011. RESULTS:
      In all cases, 3D transperineal ultrasound provided detailed information on the
      length and level of stenosis and on the integrity of the anal sphincters.
      CONCLUSIONS: Our preliminary experience suggests that 3D transperineal ultrasound
      makes it possible to plan optimal surgical treatment.

PMID- 24081549
TI  - 'Beware of the deep': the deep posterior compartment in complex/chronic leg pain.

PMID- 24081551
TI  - Enzyme activity of the PIP4K2A gene product polymorphism that is implicated in
      schizophrenia.

PMID- 24081552
TI  - [Effectiveness and Cost-Effectiveness of a Multifactorial Fall Prevention
      Programme in Nursing Homes in a Real-World Setting].
AB  - The purpose of the present study was to analyse the effectiveness and cost
      effectiveness of a multifactorial fall prevention programme in nursing home
      residents in a real-world setting. The adjusted relative risk of a femoral
      fracture was 0.82 (95% CI 0.72-0.93) in residents exposed to the fall and
      fracture prevention programme compared to residents from the control group. Given
      a willingness-to-pay of 50,000 EUR per year free of femoral fractures from a
      payer perspective the probability that the intervention is cost-effective was
      83%.

PMID- 24081550
TI  - Sex-influence of nicotine and nitric oxide on motor coordination and anxiety
      related neurophysiological responses.
AB  - RATIONALE: Nitric oxide (NO) is a messenger synthesized in both the neuronal and
      glial populations by nitric oxide synthase type 1 (NOS1). Nicotine regulates NO
      production in a sex-dependent manner, both molecules being involved in motor
      function. OBJECTIVE: The present study evaluates sex differences in motor
      coordination, general movement, and anxiety-related responses resulting from both
      constant and continuous nicotine treatment and the genetic depletion of NOS1
      activity. METHODS: Male and female mice were analyzed with the open-field and the
      rotarod tests. To understand the role of NO, knockout mice for NOS1 (NOS1-/-)
      were analyzed. Nicotine was administered continuously at a dose of 24 mg/kg/day
      via osmotic mini-pumps over 14 days because the behavioral effects elicited are
      similar to those observed with discontinuous administration. RESULTS: Data
      analyses revealed noteworthy sex differences derived from NOS1 depletion. Control
      NOS1-/- males exhibited an exacerbated anxiety-related response in relation to
      control NOS1-/- females and control wild-type (WT) males; these differences
      disappeared in the nicotine-administered NOS1-/- males. Additionally, nicotine
      administration differentially affected the horizontal movements of NOS1-/-
      females with respect to WT animals. NO depletion affected male but not female
      motor coordination improvement along the test days. However, the drug affected
      female motor coordination only at the end of the administration period.
      CONCLUSIONS: We show for the first time that NO affects motor and anxiety
      behaviors in a sex-dependent manner. Moreover, the behavioral effects of constant
      nicotine administration are dimorphic and dependent on NO production.

PMID- 24081553
TI  - [Evaluation of an Intensified Dental Preventive Programme Aimed at Children with
      Increased Caries Risk].
AB  - Our study investigated the effect of a selective intensive prevention (SIP)
      programme on dental health of pupils in comparison to a control group. While no
      differences were observed in respect to dental health of first graders, the DMF-T
      values of fourth and 6 graders participating in SIP were significantly lower.
      Concerning the psychometric variables only few differences were found. The fourth
      and 6 graders in the test group reported less dental fear than the pupils in the
      control group. 

PMID- 24081554
TI  - [School Development by Using Health Management: Indicator Toolbox as Quality
      Assurance Instrument for Self-Evaluation in Schools].
AB  - Organisational development is crucial to health promotion in schools. The
      intervention "Learning to Live Healthy" is a new school health promotion strategy
      designed to develop schools into healthy environments for all those who work and
      study there. The aim of the study "School Development by using Health Management"
      is to introduce the management instrument balanced scorecard and to develop an
      indicator toolbox. This allows schools to evaluate the achievement of objectives,
      the implementation level of the measures and the changes in their organisation
      regarding health management. 

PMID- 24081555
TI  - [Stress Prevention in Adolescence: Evaluation and Optimisation of a Setting-Based
      Programme].
AB  - The aim of the project was related to the development of a stress prevention
      programme for adolescents with a special focus on the use of the internet to
      communicate health-related topics. It could be shown that the evaluative
      programme effects were improved if a website was available in addition to a face
      to-face training. This led to more positive results with regard to knowledge
      about stress and stress prevention, satisfaction with the training, symptom
      reduction and self-efficacy. 

PMID- 24081556
TI  - [Family Caregivers as a Target Group for Health Promotion and Prevention].
AB  - Family caregivers are a target group for health promotion, due to the various
      burdens. Against this background an assessment (ARR) was developed, implemented,
      and validated in the project "Health Promotion for Elderly Family Caregiver". On
      the basis of the ARR, family caregivers received an individual, need-oriented,
      and specific offer for health promotion. In order to reach the target group
      optimally, a national health insurance company was used. 

PMID- 24081557
TI  - [Transparency of the newborn hearing screening system in Germany].
AB  - AIM: The transparency of implementation of the newborn hearing screening system
      in Germany is analysed. For this purpose it has been tested whether the current
      state can be retained and evaluated by using public accessible information
      channels. METHODS: A selective document analysis with subsequent assessment of
      the federal states was performed. In the form of a scoring system an assessment
      approach has been developed based on defined comparison criteria. The selective
      document analysis was characterised by including only documents which were
      detected through the internet and medical databases by using defined search
      terms. RESULTS: A complete survey of the current state of guideline
      implementation is not available by using public accessible information. The
      assessment of the federal states reveals an extremely heterogeneous situation
      with regard to the transparency of the implementation process in Germany. Bavaria
      has the highest score with 37 points, while Bremen has the lowest score with 3
      points. Overall, the supply of information to experts is better constituted
      compared to that to the population, and respectively, the newborn's parents.
      CONCLUSION: A meaningful evaluation of the implementation processes in the
      federal states up to now is urgently required. This is necessary both to optimise
      the process and to achieve the highest possible quality among patient-centred
      care structures nationwide.

PMID- 24081558
TI  - [Effectiveness of School-Based Life Skills Programmes on Secondary Schoolchildren
      in a High Risk Sample].
AB  - Based on a randomized controlled multicentre-design the effect of school-based
      life skills programmes was investigated in a sample of 102 classes of secondary
      schools (Hauptschulen) in northern Germany. Self-reports of 1,057 pupils showed
      positive effects of the programmes on the reduction of smoking. Pupils' life
      skills improved in the teachers' assessment. The social and the migration status
      did not moderate the results. Both pupils and teachers evaluated the programmes
      very positive.

PMID- 24081559
TI  - A cloud system for mobile medical services of traditional Chinese medicine.
AB  - Many medical centers in Taiwan have started to provide Traditional Chinese
      Medicine (TCM) services for hospitalized patients. Due to the complexity of TCM
      modality and the increasing need for providing TCM services for patients in
      different wards at distantly separate locations within the hospital, it is
      getting difficult to manage the situation in the traditional way. A computerized
      system with mobile ability can therefore provide a practical solution to the
      challenge presented. The study tries to develop a cloud system equipped with
      mobile devices to integrate electronic medical records, facilitate communication
      between medical workers, and improve the quality of TCM services for the
      hospitalized patients in a medical center. The system developed in the study
      includes mobile devices carrying Android operation system and a PC as a cloud
      server. All the devices use the same TCM management system developed by the
      study. A website of database is set up for information sharing. The cloud system
      allows users to access and update patients' medical information, which is of
      great help to medical workers for verifying patients' identification and giving
      proper treatments to patients. The information then can be wirelessly transmitted
      between medical personnel through the cloud system. Several quantitative and
      qualitative evaluation indexes are developed to measure the effectiveness of the
      cloud system on the quality of the TCM service. The cloud system is tested and
      verified based on a sample of hospitalized patients receiving the acupuncture
      treatment at the Lukang Branch of Changhua Christian Hospital (CCH) in Taiwan.
      The result shows a great improvement in operating efficiency of the TCM service
      in that a significant saving in labor time can be attributable to the cloud
      system. In addition, the cloud system makes it easy to confirm patients' identity
      through taking a picture of the patient upon receiving any medical treatment. The
      result also shows that the cloud system achieves significant improvement in the
      acupuncture treatment. All the acupuncture needles now can be removed at the time
      they are expected to be removed. Furthermore, through the cloud system, medical
      workers can access and update patients' medical information on-site, which
      provides a means of effective communication between medical workers. These
      functions allow us to make the most use of the portability feature of the
      acupuncture service. The result shows that the contribution made by the cloud
      system to the TCM service is multi-dimensional: cost-effective, environment
      protective, performance-enhancing etc. Developing and implementing such a cloud
      system for the TCM service in Taiwan symbolizes a pioneering effort. We believe
      that the work we have done here can serve as a stepping-stone toward advancing
      the TCM service quality in the future. 

PMID- 24081560
TI  - The effects of volatile anesthetics on the extracellular accumulation of
      [(3)H]GABA in rat brain cortical slices.
AB  - GABA is an inhibitory neurotransmitter that appears to be associated with the
      action of volatile anesthetics. These anesthetics potentiate GABA-induced
      postsynaptic currents by synaptic GABAA receptors, although recent evidence
      suggests that these agents also significantly affect extrasynaptic GABA
      receptors. However, the effect of volatile anesthetics on the extracellular
      concentration of GABA in the central nervous system has not been fully
      established. In the present study, rat brain cortical slices loaded with
      [(3)H]GABA were used to investigate the effect of halothane and sevoflurane on
      the extracellular accumulation of this neurotransmitter. The accumulation of
      [(3)H]GABA was significantly increased by sevoflurane (0.058, 0.11, 0.23, 0.46,
      and 0.93 mM) and halothane (0.006, 0.012, 0.024, 0.048, 0072, and 0.096 mM) with
      an EC50 of 0.26 mM and 35 MUM, respectively. TTX (blocker of voltage-dependent
      Na(+) channels), EGTA (an extracellular Ca(2+) chelator) and BAPTA-AM (an
      intracellular Ca(2+) chelator) did not interfere with the accumulation of
      [(3)H]GABA induced by 0.23 mM sevoflurane and 0.048 mM halothane. SKF 89976A, a
      GABA transporter type 1 (GAT-1) inhibitor, reduced the sevoflurane- and halothane
      induced increase in the accumulation of GABA by 57 and 63 %, respectively.
      Incubation of brain cortical slices at low temperature (17  degrees C), a
      condition that inhibits GAT function and reduces GABA release through reverse
      transport, reduced the sevoflurane- and halothane-induced increase in the
      accumulation of [(3)H]GABA by 82 and 75 %, respectively, relative to that at
      normal temperature (37  degrees C). Ouabain, a Na(+)/K(+) ATPase pump inhibitor,
      which is known to induce GABA release through reverse transport, abolished the
      sevoflurane and halothane effects on the accumulation of [(3)H]GABA. The effect
      of sevoflurane and halothane did not involve glial transporters because beta
      alanine, a blocker of GAT-2 and GAT-3, did not inhibit the effect of the
      anesthetics. In conclusion, the present study suggests that sevoflurane and
      halothane increase the accumulation of GABA by inducing the reverse transport of
      this neurotransmitter. Therefore, volatile anesthetics could interfere with
      neuronal excitability by increasing the action of GABA on synaptic and
      extrasynaptic GABA receptors. 

PMID- 24081561
TI  - Genetic risk score analysis indicates migraine with and without comorbid
      depression are genetically different disorders.
AB  - Migraine and major depressive disorder (MDD) are comorbid, moderately heritable
      and to some extent influenced by the same genes. In a previous paper, we
      suggested the possibility of causality (one trait causing the other) underlying
      this comorbidity. We present a new application of polygenic (genetic risk) score
      analysis to investigate the mechanisms underlying the genetic overlap of migraine
      and MDD. Genetic risk scores were constructed based on data from two discovery
      samples in which genome-wide association analyses (GWA) were performed for
      migraine and MDD, respectively. The Australian Twin Migraine GWA study (N =
      6,350) included 2,825 migraine cases and 3,525 controls, 805 of whom met the
      diagnostic criteria for MDD. The RADIANT GWA study (N = 3,230) included 1,636 MDD
      cases and 1,594 controls. Genetic risk scores for migraine and for MDD were used
      to predict pure and comorbid forms of migraine and MDD in an independent Dutch
      target sample (NTR-NESDA, N = 2,966), which included 1,476 MDD cases and 1,058
      migraine cases (723 of these individuals had both disorders concurrently). The
      observed patterns of prediction suggest that the 'pure' forms of migraine and MDD
      are genetically distinct disorders. The subgroup of individuals with comorbid MDD
      and migraine were genetically most similar to MDD patients. These results
      indicate that in at least a subset of migraine patients with MDD, migraine may be
      a symptom or consequence of MDD.

PMID- 24081562
TI  - 17Beta-estradiol promotes aggressive laryngeal cancer through membrane-associated
      estrogen receptor-alpha 36.
AB  - 17beta-estradiol (E2) plays a key role in tumorigenesis by enhancing cell
      survivability and metastasis through its cytoplasmic receptors. Recently, a
      variant of estrogen receptor alpha, ERalpha36 has been implicated as a
      substantial mediator of E2's proliferative and antiapoptotic effects through
      rapid membrane-associated signaling, and cancers previously regarded as hormone
      independent due to the absence of traditional receptors, may in fact be
      susceptible to E2. Despite rising from a secondary sex organ and having a clear
      gender disposition, laryngeal cancer is not uniformly accepted as hormone
      dependent, even in the face of compelling evidence of E2 responsiveness. The aim
      of this study was to further elucidate the role of E2 in the tumorigenesis of
      laryngeal cancer, both in vitro and in vivo. ERalpha36 presence was evaluated in
      membranes of the laryngeal carcinoma cell line, Hep2, as well as in laryngeal
      tumor samples. In vitro ERalpha36 was found to mediate rapid activation of
      protein kinase C and phospholipase D by E2, leading to increased proliferation
      and protection against chemotherapy-induced apoptosis. Furthermore, in response
      to E2 activation of ERalpha36, an upregulation of angiogenic and metastatic
      factors was observed. Clinical analysis of laryngeal tumors revealed a similar
      association between the amount of ERalpha36 and VEGF and indicated a role in
      lymph node metastasis. These findings present compelling evidence of ERalpha36
      dependent E2 signaling in laryngeal cancer. Thus, targeting ERalpha36 may reduce
      the deleterious effects of E2 in laryngeal cancer, ultimately suggesting the
      importance of antiestrogen therapy or the production of novel drugs that
      specifically target ERalpha36. 

PMID- 24081565
TI  - Simultaneous determination of residues in pollen and high-fructose corn syrup
      from eight neonicotinoid insecticides by liquid chromatography-tandem mass
      spectrometry.
AB  - The neonicotinoids have recently been identified as a potential contributing
      factor to the sudden decline in adult honeybee population, commonly known as
      colony collapse disorder (CCD). To protect the health of honeybees and other
      pollinators, a new, simple, and sensitive liquid chromatography-electrospray
      ionization mass spectrometry method was developed and validated for simultaneous
      determination of eight neonicotinoids, including acetamiprid, clothianidin,
      dinotefuran, flonicamid, imidacloprid, nitenpyram, thiacloprid, and thiamethoxam,
      in pollen and high-fructose corn syrup (HFCS). In this method, eight
      neonicotinoids, along with their isotope-labeled internal standards, were
      extracted from 2 g of pollen or 5 g of HFCS using an optimized quick, easy,
      cheap, effective, rugged, and safe extraction procedure. The method limits of
      detection in pollen and HFCS matrices were 0.03 ng/g for acetamiprid,
      clothianidin, dinotefuran, imidacloprid, thiacloprid, and thiamethoxam and ranged
      between 0.03 and 0.1 ng/g for nitenpyram and flonicamid. The precision and
      accuracy were well within the acceptable 20% range. Selectivity, linearity, lower
      limit of quantitation, matrix effect, recovery, and stability in autosampler were
      also evaluated during validation. This validated method has been used
      successfully in analyzing a set of pollen and HFCS samples collected for
      evaluating potential honeybee exposure to neonicotinoids.

PMID- 24081566
TI  - Single-laboratory validation of a multiplex flow cytometric immunoassay for the
      simultaneous detection of coccidiostats in eggs and feed.
AB  - Coccidiostats are authorized in the European Union (EU) to be used as poultry
      feed additives. Maximum (residue) levels (M(R)Ls) have been set within the EU for
      consumer and animal protection against unintended carry-over, and monitoring is
      compulsory. This paper describes the single-laboratory validation of a previously
      developed multiplex flow cytometric immunoassay (FCIA) as screening method for
      coccidiostats in eggs and feed and provides and compares different approaches for
      the calculation of the cut-off levels which are not described in detail within
      Commission Decision 2002/657/EC. Comparable results were obtained between the
      statistical (reference) approach and the rapid approaches. With the most rapid
      approach, the cut-off levels for narasin/salinomycin, lasalocid, diclazuril,
      nicarbazin (DNC) and monensin in egg, calculated as percentages of inhibition
      (%B/B0), were 60, 32, 76, 80 and 84, respectively. In feed, the cut-off levels
      for narasin/salinomycin, lasalocid, nicarbazin (DNC) and monensin were 70, 64, 72
      and 78, respectively, and could not be determined for diclazuril. For all
      analytes, except for diclazuril in feed, the rate of false positives (false non
      compliant) in blank samples was lower than 1 %, and the rate of false negatives
      (false compliant) at the M(R)Ls was below 5 %. Additionally, very good
      correlations (r ranging from 0.994 to 0.9994) were observed between two different
      analysers, a sophisticated flow cytometer (FlexMAP 3D((r))) and a more cost
      efficient and transportable planar imaging detector (MAGPIX((r))), hence
      demonstrating adequate transferability.

PMID- 24081567
TI  - Specific biotinylation and sensitive enrichment of citrullinated peptides.
AB  - Protein citrullination is a posttranslational modification where peptidylarginine
      is enzymatically deiminated to form peptidylcitrulline. Although the role of
      protein citrullination in both health and disease is being increasingly
      recognised, techniques available to identify citrullinated proteins and to map
      their citrullination site(s) are rare and often show poor sensitivity. Here, we
      present a sensitive technique for specific modification and selective enrichment
      of citrullinated peptides from complex biological samples. The technique is based
      on highly specific in-solution biotinylation of citrulline residues followed by
      selective enrichment of modified peptides using streptavidin beads. We
      demonstrate that a synthetic citrulline-containing peptide can be selectively
      enriched when less than 0.5 pmol is spiked into a highly heterogeneous peptide
      mixture. After enrichment, matrix-assisted laser desorption ionization-time of
      flight mass spectrometry (MALDI-TOF MS) analysis of an aliquot of the
      streptavidin eluate corresponding to theoretically 50 fmol of the spiked-in
      peptide showed a prominent signal. We further demonstrate the sensitivity of our
      technique by enrichment of citrullinated peptides from enzymatically deiminated
      myelin basic protein (MBP), when 10 pmol was spiked into a heterogeneous
      biological digest. In MALDI-TOF MS analysis, six MBP-derived citrullinated
      peptides were observed, showing the efficiency of this enrichment strategy. The
      high sensitivity combined with the remarkable specificity of the described
      technique makes it a valuable tool for elucidating citrullination in various
      biological processes.

PMID- 24081568
TI  - Receptor-based high-throughput screening and identification of estrogens in
      dietary supplements using bioaffinity liquid-chromatography ion mobility mass
      spectrometry.
AB  - A high-throughput bioaffinity liquid chromatography-mass spectrometry (BioMS)
      approach was developed and applied for the screening and identification of
      recombinant human estrogen receptor alpha (ERalpha) ligands in dietary
      supplements. For screening, a semi-automated mass spectrometric ligand binding
      assay was developed applying (13)C2, (15) N-tamoxifen as non-radioactive label
      and fast ultra-high-performance-liquid chromatography-electrospray ionisation
      triple-quadrupole-MS (UPLC-QqQ-MS), operated in the single reaction monitoring
      mode, as a readout system. Binding of the label to ERalpha-coated paramagnetic
      microbeads was inhibited by competing estrogens in the sample extract yielding
      decreased levels of the label in UPLC-QqQ-MS. The label showed high ionisation
      efficiency in positive electrospray ionisation (ESI) mode, so the developed BioMS
      approach is able to screen for estrogens in dietary supplements despite their
      poor ionisation efficiency in both positive and negative ESI modes. The assay was
      performed in a 96-well plate, and all these wells could be measured within 3 h.
      Estrogens in suspect extracts were identified by full-scan accurate mass and
      collision-cross section (CCS) values from a UPLC-ion mobility-Q-time-of-flight-MS
      (UPLC-IM-Q-ToF-MS) equipped with a novel atmospheric pressure ionisation source.
      Thanks to the novel ion source, this instrument provided picogram sensitivity for
      estrogens in the negative ion mode and an additional identification point
      (experimental CCS values) next to retention time, accurate mass and tandem mass
      spectrometry data. The developed combination of bioaffinity screening with UPLC
      QqQ-MS and identification with UPLC-IM-Q-ToF-MS provides an extremely powerful
      analytical tool for early warning of ERalpha bioactive compounds in dietary
      supplements as demonstrated by analysis of selected dietary supplements in which
      different estrogens were identified.

PMID- 24081569
TI  - [Reaching Target Groups--Shaping Accessibility].
AB  - This paper describes the public health discourse on the accessibility and access
      paths, theoretical approaches as well as factors influencing the utilisation of
      prevention and health promotion interventions, and requirements for their
      evaluation. Various projects funded by the German Federal Ministry of Education
      and Research address many aspects of accessibility and describe extensive
      experiences with access paths, approaches to information transfer, target group
      driven supply chain design, etc. Recommendations for practice and research are
      given at the end of the article. 

PMID- 24081570
TI  - [Mechanics and effects of European reference pricing for vaccines in Germany
      according to S130a Abs. 2 SGB V: an analysis using the example of influenza
      vaccines].
AB  - OBJECTIVES: On 01 January 2011 the bill for the reorganisation of the
      pharmaceutical market became effective. Since that time there is a European
      reference pricing (ERP) system for vaccines in order to bring down the German
      vaccine prices to an assumed lower European level. This study describes the
      implementation, functioning and effect of this new system. For influenza vaccines
      the impact of ERP on the price level and spread of prices is analysed. METHODS:
      The description of the mechanism is based on the law and corresponding
      regulations of the head association of sickness funds (GKV-SV). The analysis of
      vaccine prices is based on the data of the i:data report (status of 01 September
      2011) of ifap Service Institute. RESULTS: The European reference price is
      calculated as the average price of the manufacturer-selling-prices of the
      corresponding vaccine in the 4 countries of the European Union whose gross
      national income comes closest to the German one and in which the vaccine is
      distributed. The relied prices are weighted by sales and purchasing power
      parities of the respective countries. This analysis suggests that in particular
      the practical implementation of the reference price system should be further
      improved and specified. The calculation of the reference prices should ensure
      price comparability. In addition, significant problems remain in the deduction of
      discounts, because no distinction is made in the documentation of vaccinating
      doctors, whether vaccination was performed as a compulsory or statutory benefit.
      The comparison of the manufacturer-selling-prices of individual influenza
      vaccines with the corresponding reference prices shows an enlargement of the
      existing price differences, which have evolved in a competitive environment,
      after the implementation of the reference pricing -system. CONCLUSIONS: There is
      still a need for improvement in implementing the reference pricing system. In the
      most competitive vaccine market of influenza vaccines, the ERP-system lowers the
      prices, but seems to distort the market prices.

PMID- 24081571
TI  - [Status-specific differences in the occurrence of overweight and obesity in the
      transitional period from childhood to adolescence - results from the cross
      sectional German KiGGS study].
AB  - BACKGROUND: Individual studies point out that health inequalities decrease in the
      transitional period from childhood to adolescence. However, there is evidence
      that this effect can vary depending on the health aspect that is used. The
      present study analyses this effect for overweight and obesity. METHODS:
      Representative data was obtained from a subsample (3-17 years, n=14,836) of the
      German Health Interview and Examination Survey for Children and Adolescents
      (KiGGS) which was conducted by the Robert Koch Institute from May 2003 to May
      2006. Body height and weight were measured and body mass index (BMI) was
      calculated. Overweight and obesity are defined based on gender- and age-specific
      percentiles of BMI of the German reference system developed by Kromeyer-Hauschild
      and her colleagues. Socio-economic status (SES) was taken from information about
      parents' income, occupational status and education. RESULTS: Boys and girls with
      low SES show the highest prevalence of overweight and obesity in all age groups,
      those with high SES the lowest. While the results indicate a constant impact of
      SES on the risk for overweight and obesity in boys, the status differences
      increase over the age groups in girls. Regarding the whole age range, boys with
      low SES possess a 2.0-fold increased risk for overweight, and a 2.2-fold
      increased risk for obesity compared to boys with high SES. Girls from low status
      group even have a 2.8-fold risk to become overweight, and a 4.4-fold risk to
      become obese in comparison to the reference group. CONCLUSION: The findings
      reveal that SES has a significant impact on the occurrence of overweight and
      obesity in childhood and in particular adolescence. Therefore, the results
      underline the relevance of early childhood prevention in specific target groups
      and promotion of a healthy life style.

PMID- 24081572
TI  - [Health economic evaluation of health promotion - the example "fit for pisa"].
AB  - The increasing prevalence of risk factors associated with physical inactivity
      lead to an economic burden on society. The article uses the example of the
      prevention measure "fit for pisa" to investigate to what extent a full economic
      evaluation can provide a basis for decision-makers. The intervention integrated
      the daily physical education at 5 primary schools in Gottingen for the entire
      school term. The study is intended to provide information on short- and long-term
      potential savings. A process analysis identified the prevention performance from
      a societal perspective. Resource consumption was recorded in (partly)
      standardisedform and evaluated and also revealed the need for investment in
      sports halls with capacity to expand the programme to all primary schools in
      Gottingen. In the routine the implementation costs of half-day schools are 619 ?
      per student year; for all-day schools 236 ? per student year. The consideration
      of the short-term outcomes shows that TV viewing has decreased and physical
      activity has been strongly encouraged. The active life style promotion has shown
      an improvement on BMI in the medium-term. On the basis of a decision analytical
      model, a cost-benefit analysis of the program over the life course will be
      undertaken. 

PMID- 24081573
TI  - [Hospital governance and the structure of German hospital supervisory boards].
AB  - AIM OF THE STUDY: When thinking about corporate governance frequently the
      supervisory board comes to mind. The aim of this study is to investigate the
      relationship between the participation of single professions in the supervisory
      board and hospital financial performance. METHODS: Based on governance codes,
      relevant professions that should be part of the supervisory board are identified.
      With the help of a multiple regression, the relationship between the fractions of
      these professions in the supervisory board and the return on assets in the year
      2009 is examined. The sample consists of 182 hospitals. RESULTS: The study shows
      that participation of physicians in the supervisory board is related to a higher
      return on assets. Furthermore, the association between the fractions of nurses
      and politicians and hospitals financial performance is -negative. CONCLUSION: The
      composition of the supervisory board has a significant effect on hospital
      performance; it is an important issue for hospital owners. The present study
      identifies only one positive relationship between the involvement of physicians
      and financial performance. Other professions could be relevant in achieving other
      objectives. Further studies are necessary to analyse the effects on other
      dimensions of hospital performance, e. g., on quality.

PMID- 24081574
TI  - [People with dementia between home and respite care: quality assurance for cross
      over communication, a systematic review].
AB  - INTRODUCTION: To identify safety-relevant communication structures and processes
      considering the handover between home and respite care for people with dementia
      (PwD). METHOD: In a systematic review, MEDLINE, -EMBASE, Cochrane Library,
      CINAHL, PsycINFO and GeroLit were searched for publications indexed until April
      2011 including a search via Google and Google scholar. An update for publications
      indexed between May 2011 and December 2012 was added. OUTCOMES: A total of 1 832
      search results were identified and one relevant publication of a project for PwD
      to improve the handover between settings was included. With regard to that
      project, additional literature was identified. CONCLUSION: The practice-based
      project identified through the literature search could be suitable to improve
      handover communication between home and respite care for PwD after further
      validation. A large gap in the evidence with regard to the research question was
      identified.

PMID- 24081575
TI  - [Poisonings due to Substance Abuse Reported to the Poisons Information Centre
      Erfurt from 2002 to 2011].
AB  - AIM OF THE STUDY: Because of their importance for clinical toxicology,
      developments of sub-stance abuse reported to the Poisons Information Centre (PIC)
      Erfurt were investigated and compared to other reasons of human exposures.
      METHODS: A retrospective analysis of all human exposures (exposures of humans to
      substances in abuse, accidental and unknown circumstances, and suicide attempts)
      (n=125,130) from the beginning of 2002 to the end of 2011 was undertaken
      according to substance classes, reasons of exposures, symptom severity, age
      groups, and gender. RESULTS: Cases of substance abuse (3,760, 3.0% of all
      exposures) continuously increased from 252 (92 with one and 160 with multiple
      substances) in 2002 to 507 in 2011 (239 with one and 268 with multiple
      substances). In relation to all exposures, only the abuse of multiple substances
      rose significantly (p<0.001). In comparison to all substances of exposure,
      ethanol, amphetamine-type stimulants, benzodiazepines/analogues, and liquid
      ecstasy abuse significantly (p<0.005) increased while cannabis and
      Brugmansia/Datura species abuse significantly (p<0.05) decreased. Substance abuse
      significantly (p<0.001) more often caused moderate (23.7%) and severe symptoms
      (6.1%) than in suicide attempts (9.6%; 4.4%). First legal highs exposures were
      registered in 2010 and led significantly (p<0.001) more often to moderate
      symptoms (50%) than cannabis exposures (19.4%). CONCLUSIONS: The clinical
      significance of substance abuse is shown by the fact that it resulted more often
      in moderate and severe symptoms than suicide attempts. Data on substance abuse
      from PICs could supplement official annual drug reports in aspects of clinical
      toxicology.

PMID- 24081576
TI  - Pseudothrombocytopenia in a patient receiving romiplostim for immune
      thrombocytopenic purpura.

PMID- 24081577
TI  - Phase II trial to assess the safety and efficacy of clofarabine in combination
      with low-dose cytarabine in elderly patients with acute myeloid leukemia.
AB  - Previous studies have shown that clofarabine plus low-dose cytarabine (LDAC)
      could induce roughly 60 % of complete remissions (CR) with acceptable toxicity
      and induction mortality in elderly acute myeloid leukemia (AML) patients not
      suitable for intensive chemotherapy. The Programa Espanol de Tratamientos en
      Hematologia group conducted a trial for patients diagnosed with untreated AML
      aged 60 years and older, using the combination of clofarabine (20 mg/m(2) * 5
      days) plus low-dose cytarabine (20 mg/m(2) * 14 days). The protocol was flexible
      regarding the use of antifungal and antibacterial prophylaxis, and outpatient
      induction therapy was allowed. Although the planned recruitment goal was 75
      patients, only 11 patients were enrolled (median age, 74 years) after observing
      high toxicity and unacceptable mortality (46 and 73 % at 4 and 8 weeks,
      respectively). The response assessment showed three CR (27 %), three resistant
      diseases (27 %), and five induction deaths (46 %). Induction was administered in
      an outpatient modality in five patients, while antifungal and antibacterial
      prophylaxis was not given in seven and five patients, respectively. In our
      context, induction therapy with the combination of clofarabine (20 mg/m(2)) plus
      LDAC was associated with high toxicity and unacceptable mortality in elderly AML
      patients, leading to the early interruption of the trial. Tight patients'
      clinical monitoring, follow-up, and intensive supportive care seem crucial to
      achieve at least acceptable clinical outcomes in elderly AML patients receiving
      clofarabine plus LDAC. This trial is registered at www.clinicaltrials.gov as no.
      NCT01193400.

PMID- 24081578
TI  - Beware of mereologists bearing gifts: prolegomena to a medical metaphysics.
AB  - This essay considers implications of formal mereologies and ontologies for
      medical metaphysics. Edward Fried's extensional mereological account of the human
      body is taken as representative of a prominent strand in analytic metaphysics
      that has close affinities with medical positivism. I show why such accounts fail.
      First, I consider how Fried attempts to make sense of the medical case of Barney
      Clark, the first recipient of an artificial heart, and show that his analytic
      metaphysical categories do not have the right kind of fit with the case. A proper
      medical metaphysic should involve a richer two way dialogue with medicine, and it
      should not just "apply" formal accounts worked out in other settings. Second, I
      argue that any effort to account for real wholes with extensional mereological
      sums requires all sorts of ad hoc, supplementary mechanisms that do the real
      work, and the full repertoire of these mechanisms involves inconsistencies and
      semantic shifts. Finally, I consider an alternative strand of work on non
      extensional whole/part relations that is closer to medicine and that can deepen
      reflection on some core problems in bioethics, for example, associated with the
      determination of death when an organism ceases to function as a whole. In
      addition to the utility such formal ontologies have for addressing traditional
      problems such as the determination of death, philosophers of medicine should
      appreciate the increasingly influential role such formal tools are playing in the
      development of data system ontologies. Assumptions integral to these ontologies
      have far reaching implications for the way future research and practice in
      medicine will be conducted, and much greater critical reflection is needed on the
      full range of issues associated with the development and use of such medical
      ontologies. 

PMID- 24081579
TI  - Fast fitting to low resolution density maps: elucidating large-scale motions of
      the ribosome.
AB  - Determining the conformational rearrangements of large macromolecules is
      challenging experimentally and computationally. Case in point is the ribosome; it
      has been observed by high-resolution crystallography in several states, but many
      others are known only from low-resolution methods including cryo-electron
      microscopy. Combining these data into dynamical trajectories that may aid
      understanding of its largest-scale conformational changes has so far remained out
      of reach of computational methods. Most existing methods either model all atoms
      explicitly, resulting in often prohibitive cost, or use approximations that lose
      interesting structural and dynamical detail. In this work, I introduce Internal
      Coordinate Flexible Fitting, which uses full atomic forces and flexibility in
      limited regions of a model, capturing extensive conformational rearrangements at
      low cost. I use it to turn multiple low-resolution density maps, crystallographic
      structures and biochemical information into unified all-atoms trajectories of
      ribosomal translocation. Internal Coordinate Flexible Fitting is three orders of
      magnitude faster than the most comparable existing method. 

PMID- 24081580
TI  - 3did: a catalog of domain-based interactions of known three-dimensional
      structure.
AB  - The database of 3D interacting domains (3did, available online for browsing and
      bulk download at http://3did.irbbarcelona.org) is a catalog of protein-protein
      interactions for which a high-resolution 3D structure is known. 3did collects and
      classifies all structural templates of domain-domain interactions in the Protein
      Data Bank, providing molecular details for such interactions. The current version
      also includes a pipeline for the discovery and annotation of novel domain-motif
      interactions. For every interaction, 3did identifies and groups different binding
      modes by clustering similar interfaces into 'interaction topologies'. By
      maintaining a constantly updated collection of domain-based structural
      interaction templates, 3did is a reference source of information for the
      structural characterization of protein interaction networks. 3did is updated
      every 6 months. 

PMID- 24081582
TI  - Crystal structure of tRNA m1G9 methyltransferase Trm10: insight into the
      catalytic mechanism and recognition of tRNA substrate.
AB  - Transfer RNA (tRNA) methylation is necessary for the proper biological function
      of tRNA. The N(1) methylation of guanine at Position 9 (m(1)G9) of tRNA, which is
      widely identified in eukaryotes and archaea, was found to be catalyzed by the
      Trm10 family of methyltransferases (MTases). Here, we report the first crystal
      structures of the tRNA MTase spTrm10 from Schizosaccharomyces pombe in the
      presence and absence of its methyl donor product S-adenosyl-homocysteine (SAH)
      and its ortholog scTrm10 from Saccharomyces cerevisiae in complex with SAH. Our
      crystal structures indicated that the MTase domain (the catalytic domain) of the
      Trm10 family displays a typical SpoU-TrmD (SPOUT) fold. Furthermore, small angle
      X-ray scattering analysis reveals that Trm10 behaves as a monomer in solution,
      whereas other members of the SPOUT superfamily all function as homodimers. We
      also performed tRNA MTase assays and isothermal titration calorimetry experiments
      to investigate the catalytic mechanism of Trm10 in vitro. In combination with
      mutational analysis and electrophoretic mobility shift assays, our results
      provide insights into the substrate tRNA recognition mechanism of Trm10 family
      MTases. 

PMID- 24081581
TI  - Regulation of alternative splicing by local histone modifications: potential
      roles for RNA-guided mechanisms.
AB  - The molecular mechanisms through which alternative splicing and histone
      modifications regulate gene expression are now understood in considerable detail.
      Here, we discuss recent studies that connect these two previously separate
      avenues of investigation, beginning with the unexpected discoveries that
      nucleosomes are preferentially positioned over exons and DNA methylation and
      certain histone modifications also show exonic enrichment. These findings have
      profound implications linking chromatin structure, histone modification and
      splicing regulation. Complementary single gene studies provided insight into the
      mechanisms through which DNA methylation and histones modifications modulate
      alternative splicing patterns. Here, we review an emerging theme resulting from
      these studies: RNA-guided mechanisms integrating chromatin modification and
      splicing. Several groundbreaking papers reported that small noncoding RNAs affect
      alternative exon usage by targeting histone methyltransferase complexes to form
      localized facultative heterochromatin. More recent studies provided evidence that
      pre-messenger RNA itself can serve as a guide to enable precise alternative
      splicing regulation via local recruitment of histone-modifying enzymes, and
      emerging evidence points to a similar role for long noncoding RNAs. An exciting
      challenge for the future is to understand the impact of local modulation of
      transcription elongation rates on the dynamic interplay between histone
      modifications, alternative splicing and other processes occurring on chromatin. 

PMID- 24081583
TI  - cAMP protein kinase phosphorylates the Mos1 transposase and regulates its
      activity: evidences from mass spectrometry and biochemical analyses.
AB  - Genomic plasticity mediated by transposable elements can have a dramatic impact
      on genome integrity. To minimize its genotoxic effects, it is tightly regulated
      either by intrinsic mechanisms (linked to the element itself) or by host-mediated
      mechanisms. Using mass spectrometry, we show here for the first time that MOS1,
      the transposase driving the mobility of the mariner Mos1 element, is
      phosphorylated. We also show that the transposition activity of MOS1 is
      downregulated by protein kinase AMP cyclic-dependent phosphorylation at S170,
      which renders the transposase unable to promote Mos1 transposition. One step in
      the transposition cycle, the assembly of the paired-end complex, is specifically
      inhibited. At the cellular level, we provide evidence that phosphorylation at
      S170 prevents the active transport of the transposase into the nucleus. Our data
      suggest that protein kinase AMP cyclic-dependent phosphorylation may play a
      double role in the early stages of genome invasion by mariner elements. 

PMID- 24081585
TI  - [Capsaicin plasters for complex regional pain syndrome type II].

PMID- 24081586
TI  - [Burnout. Stress coping disorder and meaning of life crises].
AB  - Burnout is not a medical diagnosis but a developmental aberration which is
      associated with the risk of subsequent mental and somatic diseases. It can be
      summarized under a fatigue process with stress symptoms, societal-linked
      stressors and a driving force stress intensifier. In the mental stress circle,
      burnout presents as an accelerated vicious spiral driven by high demands.
      Therapeutic stress management encompasses improvement in life balance, cognitive
      information processing and functionality of the behavioral pattern as well as
      deceleration of the stress spiral. Burnout is also a meaning of life crisis,
      triggered by the narrowing of performance and success. The anthropological
      therapeutic approach targets an enhancement of self-conception and lifestyle.
      Other available therapy approaches for burnout include pharmacotherapy, coaching,
      management consulting and inpatient treatment. 

PMID- 24081590
TI  - Laparotomy for perforated small bowel from ingested paperclips.

PMID- 24081589
TI  - Kidney lesions in diabetic patients with normoalbuminuric renal insufficiency.
AB  - Diabetic nephropathy is a leading cause of end-stage renal disease in Japan.
      Microalbuminuria has been considered as the first clinical sign of diabetic
      nephropathy. However, recent studies demonstrated that normoalbuminuric renal
      insufficiency is not uncommon for diabetic patients, especially in type 2
      diabetes. Although the pathogenesis of normoalbuminuric renal insufficiency in
      diabetic nephropathy remains to be fully elucidated, distinct clinical and
      pathological features of diabetic patients with this finding have been reported
      as compared to those in diabetic patients with a typical clinical course. In type
      1 diabetes, more advanced glomerular lesions were found in patients with
      normoalbuminuric renal insufficiency than in patients with normoalbuminuric
      preserved renal function. In contrast, disproportionately advanced
      tubulointerstitial and vascular lesions, despite minor diabetic glomerular
      lesions, which denote the presence of diabetic kidney lesions as well as
      nephrosclerosis, were likely to be related to the development of normoalbuminuric
      renal insufficiency in some type 2 diabetic patients. In addition, long-term
      outcomes of diabetic patients with normoalbuminuric renal insufficiency remain
      controversial. Further studies to gain a better understanding of the structural
      functional relationships and natural history of diabetic patients with
      normoalbuminuric renal insufficiency may improve the benefits of therapeutic
      interventions for diabetic nephropathy. 

PMID- 24081591
TI  - Helicobacter pylori associated vitamin B12 deficiency, pernicious anaemia and
      subacute combined degeneration of the spinal cord.
AB  - A 23-year-old man presented with weakness in the lower limbs, numbness in hands
      and feet over past 6 months. Examination revealed a combination of absent ankle
      jerk, extensor plantar response and reduced sensations in a glove and stocking
      distribution. MRI of the spinal cord was distinctive of subacute combined
      degeneration (SACD) of the spinal cord. Serum vitamin B12 was low and anti
      intrinsic factor antibodies were positive. A biopsy of the stomach revealed
      intense inflammatory infiltrates in lamina propria with grade III Helicobacter
      pylori infection. Other work-up for the cause of vitamin B12 deficiency was
      unremarkable. H pylori infection triggers autoantibodies by a mechanism of
      molecular mimicry. This case report highlights H pylori as a causative agent in
      vitamin B12 deficiency and culminating in SACD of the spinal cord. H pylori
      treatment reverses the underlying pathogenesis and corrects vitamin B12 deficient
      state in selected individuals. 

PMID- 24081592
TI  - EBV-associated colonic B-cell lymphoma following treatment with infliximab for
      IBD: a new problem?
AB  - Patients with inflammatory bowel disease who do not respond to steroid therapy
      often require treatment with immunomodulators in an attempt to achieve a response
      and maintain remission. However, a major concern and controversy is whether these
      treatments are putting the patients at a significantly increased risk of
      developing lymphomas. This case reports a patient with severe ulcerative colitis
      who had been previously treated with azathioprine and infliximab, and
      subsequently developed diffuse large B-cell colonic lymphoma. 

PMID- 24081593
TI  - Catastrophic antiphospholipid syndrome (CAPS) induced by influenza A virus
      subtype H1N1.
AB  - Catastrophic antiphospholipid syndrome (CAPS) has been associated with several
      bacterial and viral infections. We presented a case report of a woman who
      presented to the emergency room, with influenza A virus subtype H1N1 which
      progressed to CAPS in the course of 17 days. We believe this is the first case
      that links CAPS with H1N1. 

PMID- 24081594
TI  - Small bowel obstruction after hand-assisted laparoscopic sigmoid colectomy for
      cancer.
AB  - Hand-assisted laparoscopic surgery (HALS) was introduced as a bridge towards
      totally laparoscopic procedures. Some concerns are raised regarding its long-term
      complications such as incisional hernia and adhesive small bowel obstruction. A
      woman was admitted with colicky central abdominal pain, distension and vomiting.
      She had a hand-assisted laparoscopic sigmoid colectomy for cancer 6 years
      earlier. Clinical examination revealed a well-healed periumbilical scar with no
      evidence of incisional hernia. The abdomen was distended with exaggerated bowel
      sounds. A CT scan showed dilated loops of small bowel with a transitional zone
      and distally collapsed bowel. A diagnostic laparoscopy revealed a twisted segment
      of small bowel that was adherent to the anterior abdominal wall at the hand-port
      closure site. This segment was released laparoscopically without the need for a
      resection. Adhesive small bowel obstruction to the hand-port site closure may
      occur years after HALS and can simply be relieved by laparoscopic exploration. 

PMID- 24081595
TI  - The calcium sign of aortic arch dissection.

PMID- 24081596
TI  - Unilateral calf hypertrophy and focal myositis induced by S1 radiculopathy:
      dramatic response to steroid treatment.
AB  - Unilateral enlargement of the calf in a 57-year-old man with S1 radiculopathy is
      described in this case report. Short tau inversion recovery-weighted imaging
      provided evidence of selective hypertrophy and a high signal intensity of the
      gastrocnemius and soleus. Histopathological analysis of the gastrocnemius
      revealed an endomysial inflammatory infiltrate and marked denervation lesions.
      Marked signs of denervation are suggestive of focal myositis secondary to
      neurogenic damage. The patient was treated with an oral corticosteroid (30
      mg/day) and the calf hypertrophy was dramatically reduced within 5 weeks. Our
      case indicates that steroid therapy should be tried because it may be a
      potentially treatable disease. 

PMID- 24081597
TI  - Uterine duplicity without communication between both hemiuteri and cervicovaginal
      atresia: importance of a thorough diagnosis before treatment.
AB  - The study described diagnostic and therapeutic processes for an exceptional
      congenital female genital anomaly involving a 15-year-old girl with progressive
      dysmenorrhoea and intense abdominal pain, and analyses pathogenesis of
      embryological anomalies associated with uterine duplicity (UD). Diagnostic
      methodology is analysed; treatment is described; and recommendations are
      provided. For the study of anomalies such as UD, we recommend the use of an
      ultrasound, vaginoscopy, MRI and laparoscopy imaging. Keeping in mind that
      hemihysterectomy should only be performed in cases with endometriosis or other
      unusual circumstances, surgical treatment should be avoided. A complete study
      based on gynaecological examination and ultrasound should be performed in
      adolescents with severe and progressive dysmenorrhoea. Based on the findings,
      imaging tests such as MRI and, if necessary, laparoscopy coinciding with
      menstruation, should be conducted before opting for surgical treatment. 

PMID- 24081598
TI  - Natural resolution of a herniated lumbar disc.

PMID- 24081599
TI  - Staged interventional and surgical management for complex low birthweight
      tetralogy of Fallot: another imperfect but legitimate strategy.
AB  - Management of spelling low weight infants with complex tetralogy of Fallot is
      often fraught. We present a 2.8-kg infant with DiGeorge syndrome and spelling
      tetralogy with non-confluent pulmonary arteries, the left pulmonary artery being
      supplied by an aberrant ductus arteriosus from the left common carotid artery. We
      performed stenting of the outflow tract and the ductus to allow this patient to
      achieve a successful elective surgical correction. 

PMID- 24081600
TI  - Eosinophilic enteritis: a rare cause of diarrhoea.
AB  - We report a case of a healthy young man presenting with 1-week history of
      diarrhoea, acute abdominal pain and weight loss. Laboratory investigation showed
      very high peripheral eosinophils levels. After exclusion of the other causes of
      eosinophilia, a histological bowel sample analysis revealed marked eosinophilic
      infiltration of a small bowel mucosal layer which confirmed the suspicion of
      eosinophilic enteritis. Unlike most of the described cases, this patient did not
      require any specific treatment. Eosinophilic gastroenteritis is a rare and
      heterogeneous disease that is probably underdiagnosed in clinical practice
      because it requires a high degree of suspicion and an endoscopic biopsy for
      definite diagnosis. 

PMID- 24081601
TI  - Hepatocellular carcinoma in a young man with resting and postural tremors.
AB  - A 25-year-old man who was normally fit and well, presented with a 2-year history
      of progressively worsening tremor. His tremor was generalised, affecting head,
      neck and all four limbs. One of the patient's brothers had suffered from similar
      problems, but never sought medical attention. Examination revealed a generalised
      tremor, of greater amplitude on the patient's left side, which increased in its
      amplitude upon exertion. Slit-lamp examination revealed bilateral Kayser
      Fleischer rings and serum caeruloplasmin was found to be low, while 24 h urinary
      copper excretion was elevated. A diagnosis of Wilson's disease was made and an
      abdominal ultrasound was performed, revealing evidence of portal hypertension and
      a hyperechoic hepatic nodule, later confirmed to be hepatocellular carcinoma. The
      patient underwent partial hepatic resection and was started on D-penicillamine. 

PMID- 24081602
TI  - Non-syndromic brachydactyly, known as Shamoji-yubi or Mamushi-yubi in Japan.

PMID- 24081603
TI  - A 39-year-old woman with spots covering her body.

PMID- 24081604
TI  - Activities and specificities of homodimeric TALENs in Saccharomyces cerevisiae.
AB  - The development of highly efficient genome engineering reagents is of paramount
      importance to launch the next wave of biotechnology. TAL effectors have been
      developed as an adaptable DNA binding scaffold that can be engineered to bind to
      any user-defined sequence. Thus, TAL-based DNA binding modules have been used to
      generate chimeric proteins for a variety of targeted genome modifications across
      eukaryotic species. For example, TAL effectors fused to the catalytic domain of
      FokI endonuclease (TALENs) were used to generate site-specific double strand
      breaks (DSBs), the repair of which can be harnessed to dictate user-desired,
      genome-editing outcomes. To cleave DNA, FokI endonuclease must dimerize which can
      be achieved using a pair of TALENs that bind to the DNA targeted in a tail-to
      tail orientation with proper spacing allowing the dimer formation. Because TALENs
      binding to DNA are dependent on their repeat sequences and nucleotides binding
      specificities, homodimers and heterodimers binding can be formed. In the present
      study, we used several TALEN monomers with increased repeats binding degeneracy
      to allow homodimer formation at increased number of genomic loci. We assessed
      their binding specificities and genome modification activities. Our results
      indicate that homodimeric TALENs could be used to modify the yeast genome in a
      site-specific manner and their binding to the promoter regions might modulate the
      expression of target genes. Taken together, our data indicate that homodimeric
      TALENs could be used to achieve different engineering possibilities of
      biotechnological applications and that their transcriptional modulations need to
      be considered when analyzing their phenotypic effects. 

PMID- 24081605
TI  - The Arabic Mood and Feelings Questionnaire: psychometrics and validity in a
      clinical sample.
AB  - The purpose of this study was to provide clinicians in the Arab World with a
      child and adolescent depression screening tool. Child and parent versions of the
      Mood and Feelings Questionnaire (CMFQ and PMFQ respectively) were translated to
      Arabic and administered along with the Strengths and Difficulties Questionnaire
      (SDQ) to 30 children and adolescents and with mood disorders and 76 children and
      adolescents with other psychiatric disorders seeking treatment at a child and
      adolescent psychiatry clinic. DSM-IV diagnoses were generated through clinical
      interviews by a psychiatrist blinded to self-reports. Internal consistency for
      both versions was excellent with moderate inter-informant agreement and good
      convergent validity with the SDQ emotional symptoms subscales on the child and
      parent forms. The CMFQ and PMFQ significantly differentiated between currently
      depressed participants and those with other psychiatric disorders. CMFQ scores
      were a stronger predictor of categorization into depressed and non-depressed
      groups than the PMFQ. Two modes of cutoffs were calculated with one favoring
      sensitivity (a score of 26 for the CMFQ and 22 for the PMFQ) and another favoring
      specificity (a score of 31 for the CMFQ and 28 for the PMFQ). 

PMID- 24081606
TI  - Spatial and temporal analysis of infant mortality from congenital malformations
      in Brazil (1996-2010).

PMID- 24081607
TI  - Spectrum of pathogens of in-patient children and youths with community acquired
      pneumonia: a 3 year survey of a community hospital in Vienna, Austria.
AB  - BACKGROUND: No actual data are available on the epidemiology and morbidity of
      community acquired pneumonia (CAP) in youths and children in Vienna, Austria.
      OBJECTIVE: The objective was to determine the epidemiology of CAP and morbidity
      of children hospitalized due to CAP in a tertiary care facility. METHODS: During
      three winter seasons youths and children hospitalized due to CAP were enrolled.
      Testing for viral and bacterial pathogens of pneumonia was performed in a routine
      clinical setting. Blood cultures were performed; respiratory viruses, Mycoplasma
      pneumoniae and Chlamydia pneumoniae were searched for by an established Real Time
      polymerase chain reaction (PCR) panel. Clinical signs and indices of inflammation
      were documented. RESULTS: Out of 279 children and youths with CAP a causative
      agent could be detected in 190 (68 %). Viruses and bacteria were diagnosed in 107
      (57 %) and 58 patients (30 %), respectively. Co-infection was found in 20
      patients (10 %), Mycoplasma pneumoniae or Clamydia pneumoniae in 16 cases (8 %).
      In seven patients blood cultures were positive. C-reactive protein (CRP) was
      significantly higher in children with positive Streptococcus pneumoniae antigen
      (SPAG) than with viral infection and/or co-infection. Clinical parameters showed
      no statistically significant differences. C. pneumoniae and M. pneumoniae were
      only diagnosed in children and youths with 5 years and older. CONCLUSIONS:
      Testing for pathogens in CAP in clinical routine achieves a high recovery rate.
      Blood cultures are rarely helpful, but the molecular testing for viruses seemed
      to be helpful to establish the diagnosis.

PMID- 24081608
TI  - Docking and quantitative structure-activity relationship of oxadiazole derivates
      as inhibitors of GSK3beta.
AB  - The binding modes of 42 oxadiazole derivates inside glycogen synthase kinase 3
      beta (GSK3beta were determined using docking experiments; thus, the preferred
      active conformations of these inhibitors are proposed. We found that these
      compounds adopt a scorpion-shaped conformation and they accept a hydrogen bond
      (HB) from the residue Val135 of the GSK3beta ATP-binding site hinge region. In
      addition, quantitative structure-activity relationship (QSAR) models were
      constructed to explain the trend of the GSK3beta inhibitory activities for the
      studied compounds. In a first approach, three-dimensional (3D) vectors were
      calculated using docking conformations and, by using multiple-linear regression,
      we assessed that GETAWAY vectors were able to describe the reported biological
      activities. In other QSAR approach, SMILES-based optimal descriptors were
      calculated. The best model included three-SMILES elements SSSbeta leading to the
      identification of key molecular features that contribute to a high GSK3beta
      inhibitory activity.

PMID- 24081609
TI  - Thermoresponsive dendronized polyprolines via the "grafting to" route.
AB  - The first and second generations of dendronized polyprolines P3G1, P3G2, and P4G1
      are prepared via the "grafting to" route, and their thermoresponsive properties
      and helical conformations investigated. High molar masses of polyproline main
      chains carrying azido groups are achieved first by polycondensation of peptide
      precursors through activated ester strategy. Oligoethylene glycol dendrons cored
      with alkyne are then attached onto the main chains through click reaction. These
      polymers are found to be thermoresponsive. Circular dichroism spectroscopy
      investigation indicates, in contrast to P3G2 and P4G1 which adopt the expected
      PPII conformation in aqueous conditions, P3G1 prefers to adopt PPI helical
      conformation, and this conformation is stable within the measured time period and
      temperature range. 

PMID- 24081610
TI  - AtHSP17.8 overexpression in transgenic lettuce gives rise to dehydration and salt
      stress resistance phenotypes through modulation of ABA-mediated signaling.
AB  - KEY MESSAGE: Transgenic Arabidopsis and lettuce plants overexpressing AtHSP17.8
      showed ABA-hypersensitive but abiotic stress-resistant phenotypes. ABA treatment
      caused a dramatic induction of early ABA-responsive genes in AtHSP17.8 
      overexpressing transgenic lettuce. Plant small heat shock proteins function as
      chaperones in protein folding. In addition, they are involved in responses to
      various abiotic stresses, such as dehydration, heat and high salinity in
      Arabidopsis. However, it remains elusive how they play a role in the abiotic
      stress responses at the molecular level. In this study, we provide evidence that
      Arabidopsis HSP17.8 (AtHSP17.8) positively regulates the abiotic stress responses
      by modulating abscisic acid (ABA) signaling in Arabidopsis, and also in lettuce,
      a heterologous plant when ectopically expressed. Overexpression of AtHSP17.8 in
      both Arabidopsis and lettuce leads to hypersensitivity to ABA and enhanced
      resistance to dehydration and high salinity stresses. Moreover, early ABA
      responsive genes, ABI1, ABI5, NCED3, SNF4 and AREB2, were rapidly induced in
      AtHSP17.8-overexpressing transgenic Arabidopsis and lettuce. Based on these data,
      we propose that AtHSP17.8 plays a crucial role in abiotic stress responses by
      positively modulating ABA-mediated signaling in both Arabidopsis and lettuce.
      Moreover, our results suggest that stress-tolerant lettuce can be engineered
      using the genetic and molecular resources of Arabidopsis.

PMID- 24081611
TI  - Signaling molecules and cell death in Melissa officinalis plants exposed to
      ozone.
AB  - KEY MESSAGE: The study focuses on the interaction between reactive oxygen species
      and hormones that regulate the programmed cell death in plants of Melissa
      officinalis exposed to ozone. Interaction between hormone and redox signaling
      pathways has been investigated in ozone-stressed (200 ppb, 5 h) lemon balm to
      verify if the response resembles the biotic defense reactions. In comparison to
      controls, plants exhibited foliar injury and the cell death was induced by (1)
      biphasic production of hydrogen peroxide and superoxide radical; (2) hormonal
      regulation of ozone-induced lesion formation with a significant production of
      ethylene, salicylic, jasmonic and abscisic acid; (3) ozone degradation to
      reactive oxygen species and their detoxification by some enzymatic (such as
      superoxide dismutase) and non-enzymatic antioxidant systems (such as ascorbic
      acid, glutathione and carotenoids), that worked in cooperation without providing
      a defense against free radicals (such as confirmed by the modification of the
      antioxidant properties of leaf tissue). This integrated view showed that reactive
      oxygen species interact with hormonal signaling pathway regulating cell death and
      the sensitivity of lemon balm to ozone.

PMID- 24081612
TI  - Characterization of two tomato AP2/ERF genes, SlCRF1 and SlCRF2 in hormone and
      stress responses.
AB  - KEY MESSAGE: SlCRF1 and SlCRF2 are expressed throughout the plant, prominently in
      vascular tissue. Each SlCRF has a distinct pattern of cytokinin induction and
      regulation by abiotic stresses in different organs. Cytokinin is an essential
      plant hormone involved in the regulation of many growth and developmental
      processes. While many cytokinin signaling pathway components have been well
      characterized, the cytokinin response factors (CRFs) that form a branch of this
      pathway are less well understood. This study examines the tomato (Solanum
      lycopersicum (L.)) CRF genes, SlCRF1 and SlCRF2 presenting a detailed and novel
      characterization of their developmental expression patterns, transcriptional
      regulation by hormones particularly cytokinin, and response to abiotic stresses.
      Both SlCRF1 and SlCRF2 were predominantly expressed in vasculature in tissues
      throughout the plant, with an overall trend for greater SlCRF2 expression in
      younger organs. Hormone regulation of SlCRF1 and SlCRF2 transcripts is primarily
      by cytokinin, which induced both SlCRFs in different organs over a range of
      developmental stages. The strongest cytokinin induction was found in leaves, with
      SlCRF2 induced to a higher level than SlCRF1. Examination of SlCRF transcripts
      during abiotic stress responses revealed that SlCRF1 and SlCRF2 have distinct
      patterns of regulation from each other and between leaves and roots. Novel
      connections between SlCRFs and stresses were found in particular including a
      strong induction of SlCRF1 by cold stress and a strong induction of SlCRF2 by
      oxidative stress in roots and unique patterns of induction/repression linking
      both SlCRFs to drought stress and response during recovery. Overall, this study
      provides a clear picture of SlCRF1 and SlCRF2 expression patterns across tissues
      during development and in response to cytokinin and specific stresses, indicating
      their importance in plant growth and environmental responses.

PMID- 24081613
TI  - Budget impact of parenteral iron treatment of iron deficiency: methodological
      issues raised by using real-life data.
AB  - OBJECTIVES: Iron deficiency is common in pregnancy, postpartum, inflammatory
      bowel disease, chronic kidney disease, chronic heart failure, heavy uterine
      bleeding, cancer and following surgery. We estimate the budget impact (BI) on the
      Swiss mandatory health insurance associated with substituting iron sucrose
      (standard) with ferric carboxymaltose (new treatment) using real-life data.
      METHODS: Resource use was based on recent primary data (Polyquest Prescriber
      Analysis, Anemia Patient Record Study in Switzerland). Personnel costs were
      estimated using the Swiss Tarmed fee-for-service reimbursement system. Drug costs
      and costs of materials used were based on official tariffs (Spezialitatenliste,
      MiGeL). Actual IMS sales data of both products were used to verify the BI model
      (1 CHF ~ 1 USD, Jan 2013). RESULTS: Ferric carboxymaltose was associated with
      cost savings of 30-44 % per patient per treatment cycle compared to iron sucrose.
      Costs per 200/500/1,000 mg total dosage treatment cycle were CHF 101/210/420 for
      ferric carboxymaltose and CHF 144/375/721 for iron sucrose. This results in cost
      savings of CHF 22-31 million across all indications in 2009. Savings were driven
      by personnel cost reductions (application time and number of applications).
      Sensitivity analyses confirmed these cost savings, even for the higher
      application costs of ferric carboxymaltose, with minimum savings of CHF 17
      million per year. CONCLUSIONS: Treating iron deficiency involves substantial
      costs to the Swiss MHI which may be reduced by substituting iron sucrose with
      ferric carboxymaltose. The use of real-life data raises methodological questions
      about the fundamental compatibility of this data with the conceptual framework of
      BI analysis.

PMID- 24081614
TI  - Isolation and fractionation of gill cells from freshwater (Lasmigona costata) and
      seawater (Mesodesma mactroides) bivalves for use in toxicological studies with
      copper.
AB  - Gills cells of the freshwater mussel Lasmigona costata and the seawater clam
      Mesodesma mactroides were isolated (mussel: chemical dissociation; clam:
      mechanical dissociation) and fractionated (Percoll gradient) into Fractions I and
      II. Mitochondrial dyes (DASPEI: mussel; MitoTracker((r)): clam) and Na(+), K(+)
      ATPase activity measurement were used to distinguish between cells of Fractions I
      and II. For mussel and clam, 80.5 +/- 1.5 and 48.3 +/- 3.2 % of cells were in
      Fraction II, respectively. For both species, cells of Fraction II had higher
      fluorescence emission and higher enzyme activity than those of Fraction I, being
      characterized as 'cells rich in mitochondria'. Cells of Fraction II were kept in
      saline solutions approximating the ionic composition of hemolymph either under
      control conditions (no Cu addition) or exposed (3 h) to copper (Cu: 5, 9 and 20
      MUg Cu/L). Cell viability and Cu and Na(+) content were measured. For both
      species, Cu content was higher and Na(+) content was lower in cells exposed to 20
      MUg Cu/L. Furthermore, a strong negative correlation was observed between cell
      Na(+) and Cu content in the two bivalve species, indicating a possible
      competition between Cu and Na(+) for ion-transporting mechanisms or binding sites
      at gill cells of Fraction II. Considering that Cu is an ionoregulatory toxicant
      in aquatic invertebrates, these preliminary toxicological data support the idea
      of using isolated gill cells rich in mitochondria to study the mechanisms
      underlying the acute toxicity of waterborne Cu in freshwater and marine bivalves.

PMID- 24081615
TI  - Response to methylene blue does not have to be considered only as rescue therapy
      for distributive shock.

PMID- 24081616
TI  - Electronic pharmacopoeia: a missed opportunity for safe opioid prescribing
      information?
AB  - Errors in prescribing of dangerous medications, such as extended release or long
      acting (ER/LA) opioid forlmulations, remain an important cause of patient harm.
      Prescribing errors often relate to the failure to note warnings regarding
      contraindications and drug interactions. Many prescribers utilize electronic
      pharmacopoeia (EP) to improve medication ordering. The purpose of this study is
      to assess the ability of commonly used apps to provide accurate safety
      information about the boxed warning for ER/LA opioids. We evaluated a convenience
      sample of six popular EP apps available for the iPhone and an online reference
      for the presence of relevant safety warnings. We accessed the dosing information
      for each of six ER/LA medications and assessed for the presence of an easily
      identifiable indication that a boxed warning was present, even if the warning
      itself was not provided. The prominence of precautionary drug information
      presented to the user was assessed for each app. Provided information was
      classified based on the presence of the warning in the ordering pathway, located
      separately but within the prescribers view, or available in a separate screen of
      the drug information but non-highlighted. Each program provided a consistent
      level of warning information for each of the six ER/LA medications. Only 2/7
      programs placed a warning in line with dosing information (level 1); 3/7 programs
      offered level 2 warning and 1/7 offered level 3 warning. One program made no
      mention of a boxed warning. Most EP apps isolate important safety warnings, and
      this represents a missed opportunity to improve prescribing practices. 

PMID- 24081617
TI  - Transmission of acceleration from a synchronous vibration exercise platform to
      the head.
AB  - Exercise vibration platforms are becoming commonplace in homes and fitness
      centers. However, excessive mechanical energy transferred to the head and eye can
      cause injury. The purpose of this study was to evaluate how changes in platform
      frequency and knee flexion angle affect acceleration transmission to the head.
      Participants (N=12) stood on a whole-body vibration platform with knee flexion
      angles of 0 degrees , 20 degrees , and 40 degrees  to evaluate how changes in
      knee flexion affected head acceleration. 7 specific platform frequencies were
      tested between 20-50 Hz at 2 peak-to-peak displacement settings (1 and 2 mm
      nominal). Accelerations were measured with triaxial accelerometers at the
      platform and head to generate transmissibility ratios. Platform-to-head
      transmissibility was not significantly different between the 2 platform peak-to
      peak amplitudes (P>0.05). Transmissibility measures varied depending on platform
      frequency and knee angle (P < 0.05). Flexing the knees resulted in reduced head
      transmissibility at all frequencies (P<0.05). Platform-to-head transmissibility
      values exceeded 1.0 at both 20 and 25 Hz platform vibration frequencies with the
      knees in full extension. To reduce the risk of injury to structures of the head
      during vibration exercise, using platforms frequencies below 30 Hz with small
      knee flexion angles (< 40 degrees ) should be avoided. 

PMID- 24081618
TI  - The use of velodrome tests to evaluate aerodynamic drag in professional cyclists.
AB  - The purpose of this study was to analyse the validity, reliability and
      sensitivity of velodrome tests to detect small changes in aerodynamic drag in
      cycling. 12 professional cyclists were assessed to obtain the drag area (SCx)
      during wind tunnel and velodrome tests. Incremental and steady-state protocols
      were performed in the velodrome with a portable power meter, and 6 bicycle
      positions were analysed and compared that involved lowering the handlebars and
      advancing the pads between 2-5 cm. A significant relationship (r=0.88, p<0.001)
      between the SCx in the wind tunnel and velodrome tests was found (0.240 +/- 0.007
      and 0.237 +/- 0.008 m2, respectively). The velodrome tests underestimated the SCx
      (0.0035 +/- 0.0038 m2 and p<0.01), which decreased (p<0.001) when the bicycle
      speed increased (0.0013 m2 each 1 km . h(-1)). The SCx values showed high
      reliability during the steady-state (r=0.99, p<0.001) and incremental protocols
      (r=0.94, p<0.001). Small changes in the aerodynamic position affected the SCx
      (p<0.001), which decreased by 0.011 +/- 0.007 m2 (4.6 +/- 2.9%, 95% CI=2.7-6.4%).
      In conclusion, the validity, reliability and sensitivity of velodrome tests to
      detect small changes in aerodynamic drag in cycling were demonstrated. Although
      SCx values were not interchangeable between different studies, the velodrome
      tests presented advantages with respect to the wind tunnel tests.

PMID- 24081619
TI  - Reliability and validity of a new maximal anaerobic shuttle running test.
AB  - The purpose of this study was twofold: first to assess the relative and absolute
      reliability of a new Maximal Anaerobic Shuttle Running Test (MASRT), and second
      to evaluate the criterion validity of the MASRT. 16 team sport players
      participated in this study. The velocity (VMASRT) and the number of shuttles
      achieved at volitional exhaustion were measured. To assess the reliability of the
      MASRT, each player performed the MASRT twice, on separate days. The criterion
      validity of the MASRT was determined by examining the relationship between MASRT
      indices and the Wingate test (WingT) performances. Results showed no difference
      between test-retest MASRT scores for VMASRT and the number of shuttles (P>0.05).
      The intraclass correlation coefficients (ICC) values for VMASRT and Shuttle
      number were 0.84 and 0.80, respectively. The coefficients of variation (CV) and
      the mean difference (bias)+/-the 95% limits of agreement for the same variables
      were 3.6 and 12.9%, and 0.02+/-0.37m.s-1 and 0.3+/-6.7, respectively. The
      strongest correlation was found between mean power output relative to body mass
      (MPO) measured during the WingT and VMASRT (r=0.77, P<0.001). The MASRT
      constitutes a reliable and valid field tool for assessing short term repeated
      running capacity of team sport players. 

PMID- 24081620
TI  - Perceived exertion, time of immersion and physiological correlates in
      synchronized swimming.
AB  - This study examined the relationship between ratings of perceived exertion (RPE,
      CR-10), heart rate (HR), peak blood lactate (La peak), and immersion (IM)
      parameters in 17 elite synchronized swimmers performing 30 solo and duet routines
      during competition. All were video recorded (50 Hz) and an observational
      instrument was used to time the IM phases. Differences in the measured variables
      were tested using a linear mixed-effects model. RPE was 7.7 +/- 1.1 and did not
      differ among routines, and neither did any of the HR parameters. There were
      differences among routines in La peak (F3,7=16.5; P=0.002), number of IM
      (F3,15=14.0; P<0.001), total time immersed (F3,16=26.6; P<0.001), percentage of
      time immersed (F3,13=6.5; P=0.007) and number of IM longer than 10 s (F3,19=3.0;
      P=0.04). RPE correlated positively to HR pre-activation, range of variation and
      recovery, IM parameters and La peak, and inversely to minimum and mean HR. A
      hierarchical multiple linear regression (MLR) model (number of IM >10 s, HR
      recovery, minimum HR, and La peak) explained 62% RPE variance (adj. Rm 2=0.62;
      P<0.001). A stepwise MLR model (La peak, mean IM time and pre-exercise HR)
      explained 46% of performance variance (adj. Rm 2=0.46; P<0.001). Findings
      highlight the psycho-physical stress imposed by the combination of intense
      dynamic exercise with repeated and prolonged apnea intervals during SS events.

PMID- 24081621
TI  - Effect of low-compression balls on wheelchair tennis match-play.
AB  - The purpose of this study was to compare court-movement variables and
      physiological responses to wheelchair tennis match-play when using low vs.
      standard compression tennis balls. Eleven wheelchair basketball players were
      monitored during repeated bouts of tennis (20 min) using both ball types. Graded
      and peak exercise tests were completed. For match-play, a data logger was used to
      record distance and speed. Individual linear heart rate oxygen consumption
      relationships were used to estimate match-play oxygen uptake. Significant main
      effects for ball type revealed that total distance (P<0.05), forward distance
      (P<0.05), and average speed (P<0.05) were higher for play using a low-compression
      ball. A lower percentage of total time was spent stationary (P<0.001), with
      significantly more time spent at speeds of 1-1.49 (P<0.05), 1.5-1.99 (P<0.05) and
      2.0-2.49 (P<0.05) m ? sec(-1) when using the low-compression ball. Main effects
      for physiological variables were not significant. Greater total and forward
      distance, and higher average speeds are achieved using a low-compression ball.
      The absence of any difference in measured HR and estimated physiological
      responses would indicate that players move further and faster at no additional
      mean physiological cost. This type of ball will be useful for novice players in
      the early phases of skill development.

PMID- 24081622
TI  - Acute hormonal responses before and after 2 weeks of HIT in well trained junior
      triathletes.
AB  - The aim was to compare the acute hormonal response to a single HIT session at the
      beginning and end of a HIT shock microcycle. 13 male junior triathletes (15.8+/
      1.8 yrs.) performed 16 HIT sessions within a 2 week period. Venous blood samples
      were collected before and after the first and last HIT session. Significant
      increases in cortisol (first session +89.7%; last session +70.3%) and hGH (first
      session +435.1%; last session +314.6%) concentrations were observed after both
      training sessions (P<0.05). The acute responses of cortisol, hGH, T3, and fT3
      were not different between the first and last HIT sessions (P=1.00). Although no
      acute changes in testosterone were detected after the training sessions,
      testosterone concentrations were significantly higher at all time points (62.6
      80.1%) during the last compared to first training session (P<=0.001). Findings
      from the present study reveal that 16 sessions of HIT led to significant
      increases in baseline concentrations of serum testosterone. This might indicate a
      heightened anabolic state even in junior triathletes. Based on the hormonal data,
      we conclude that at the end of this 2 week microcycle no familiarization effect
      was evident and that the training stimulus produced by HIT was still great enough
      to "stress" the athletes and induce positive training adaptations. 

PMID- 24081623
TI  - Genetic variations in the myostatin gene (MSTN) in New Zealand sheep breeds.
AB  - Myostatin, which is also known as growth and differentiation factor 8 (GDF8),
      acts as a negative regulator of skeletal muscle growth. Variation in the
      myostatin gene (MSTN) has been associated with variation in muscularity in many
      animals including sheep. Polymerase chain reaction-single strand conformational
      polymorphism (PCR-SSCP) analysis was used to investigate MSTN in a diverse range
      of sheep breeds including the New Zealand (NZ) Romney, Coopworth, Corriedale,
      Dorper, Perendale, Suffolk, Merino, Dorset Down, Poll Dorset, Texel and other NZ
      cross-bred sheep. A total of 28 nucleotide substitutions were identified from
      nucleotide c.-1199 in the promoter region to c.*1813 (based on NCBI GenBank
      accession number DQ530260) and including the well-described substitution
      c.*1232G>A (MSTN g+6223G>A). Of these 28 substitutions, 3 were located in the
      promoter region, 3 in the 5'UTR, 11 in intron 1, 5 in intron 2 and 5 in the
      3'UTR. One substitution in exon 1 (c.101G>A) potentially results in an amino acid
      substitution of glutamic acid (Glu) with glycine (Gly) at codon 34. Ten of these
      substitutions have not been reported previously. The genetic variation revealed
      in this study suggests this gene is more variable than hitherto reported and
      provides a foundation for future research into how this variation affects muscle
      and growth traits. 

PMID- 24081624
TI  - Loeffler's endocarditis with biventricular mural thrombi.
AB  - A 42-year-old man presented to clinic with 1-week history of cough, malaise, loss
      of appetite and fever. Symptoms started acutely with cough and generalised
      weakness followed by fever, chills, nausea, vomiting and diarrhoea. He has been
      healthy before with no chronic illnesses. Further workup disclosed, leucocytosis
      with 87% eosinophilia, bilateral lung infiltrate, deep venous thrombosis,
      pulmonary embolism and both right and left biventricular mural thrombi. Extensive
      workup was done and was consistent with hypereosinophilic syndrome, which
      explained all his clinical findings. The patient was started on high-dose
      steroids and responded very well with a complete resolution of symptoms over the
      course of a few weeks. 

PMID- 24081625
TI  - Mental health-care utilization in survivors of childhood cancer and siblings: the
      Swiss childhood cancer survivor study.
AB  - PURPOSE: We aimed to (1) describe the utilization of mental health-care in
      survivors and siblings, the association with severity of distress, and visits to
      other professionals in distressed survivors not utilizing mental health-care; and
      (2) identify factors associated with utilization of mental health-care in
      distressed survivors. METHODS: Within the Swiss Childhood Cancer Survivor Study,
      we sent postal questionnaires to all participants aged <16 years at diagnosis
      (1976-2003), who survived >=5 years after diagnosis and were aged >=16 years at
      study. Survivors and siblings could indicate if they utilized mental health-care
      in the past year. Psychological distress was assessed with the Brief Symptom
      Inventory-18 (BSI-18). Participants with scores T >= 57 on two of three scales or
      the Global Severity Index were considered distressed. RESULTS: We included 1,602
      survivors and 703 siblings. Overall, 160 (10 %) and 53 (8 %), utilized mental
      health-care and 203 (14 %) and 127 (14 %) were considered distressed. Among
      these, 69 (34 %) survivors and 20 (24 %) siblings had utilized mental health
      care. Participants with higher distress were more likely to utilize mental health
      care. Distressed survivors not utilizing mental health-care were more likely to
      see a medical specialist than nondistressed. In the multivariable regression,
      factors associated with utilizing mental health-care were higher psychological
      distress and reporting late effects. CONCLUSIONS: Our results underline the
      importance of developing interventional programs and implementing psychological
      screening in follow-up of survivors. It is also important to systematically
      address siblings' needs. In follow-up, patients at risk should be informed about
      existing possibilities or advised to visit mental health professionals.

PMID- 24081626
TI  - Valgus osteotomy by external fixation for treatment for developmental coxa vara.
AB  - Valgus subtrochanteric osteotomy is the standard surgical treatment for coxa
      vara. Nevertheless, there is no consensus on the method of fixation and osteotomy
      technique. There are some reports on employing rigid internal fixation methods
      that preclude the need of postoperative immobilization. This is a technical
      description of a valgus osteotomy performed using external fixation with
      preoperative and postoperative data on a cohort of 9 patients. In this study, 9
      hips in 9 patients with the diagnosis of developmental coxa vara underwent a
      subtrochanteric osteotomy with stabilization by an external fixator. The planned
      correction angle was obtained for all 9 patients with the osteotomies healing
      primarily. Radiographic analysis showed an improvement in Hilgenreiner's
      epiphyseal angle and the neck-shaft angle. There were no major complications
      associated with use of this method of stabilization. Minimal access surgery using
      external fixation for a valgus osteotomy of the proximal femur is safe and
      effective for the treatment for coxa vara and limb length discrepancy. It has
      potential advantages over commonly used open techniques and provides available
      alternative to currently applied methods used for fixation of proximal femoral
      osteotomies. 

PMID- 24081627
TI  - The effects of exposure to titanium dioxide nanoparticles during lactation period
      on learning and memory of rat offspring.
AB  - Nanoscale titanium dioxide (TiO2), which is massively produced and widely used in
      living environment, seems to have a potential risk on human health. The central
      nervous system (CNS) is the potential susceptible target of nanoparticles, but
      the studies on this aspect are limited so far. The aim of this study was to
      evaluate the effects of exposure to TiO2 nanoparticles during lactation period on
      learning and memory of offspring. Lactating Wistar rats were exposed to TiO2
      nanoparticles (100 mg/kg; gavage) for 21 days. The Morris water maze and passive
      avoidance tests showed that the exposure to TiO2 nanoparticles could
      significantly impair the memory and learning in the offspring. Therefore, the
      application of TiO2 nanoparticles and the effects of their exposure, especially
      during developmental period on human brain should be cautious.

PMID- 24081628
TI  - Antioxidant profile of constituents isolated from Polygonatum verticillatum
      rhizomes.
AB  - The purpose of the current study was to estimate the antioxidant profile of two
      compounds, diosgenin and santonin, isolated from Polygonatum verticillatum
      rhizomes. Stable free radical, 2, 2-diphenyl-1-picrylhydrazyl and reducing power
      assays were employed for this purpose. The results showed profound free radical
      scavenging effect of both diosgenin and santonin in a concentration-dependent
      manner. The calculated half maximal inhibitory concentration (IC50) values for
      both diosgenin and santonin was 65.80 and 50.03 MUg/ml, respectively. Similarly,
      in reducing power assay, diosgenin and santonin exhibited marked quenching
      effect. The corresponding IC50 values for both the compounds were 62.10 and 46.40
      MUg/ml, respectively. In conclusion, both the isolated compounds have strong
      antioxidant potential, which is consistent with the results of the extracts of
      the plant. 

PMID- 24081629
TI  - In vitro assessment of cytogenetic and oxidative effects of alpha-pinene.
AB  - alpha-Pinene (alpha-pinene), a bicyclic monoterpene, is present in the oils of
      many species of coniferous trees, most notably the pine, and is known for its
      diverse biological properties such as antimicrobial, anti-inflammatory,
      antiproliferative and antioxidant. However, there are limited data on the
      cytogenetic and antioxidant effects of alpha-pinene in cultured human blood cells
      (n = 5) for the first time. The purpose of this study was to investigate the
      genetic, oxidative, and cytotoxic effects of alpha-pinene in cultured human blood
      cells (n = 5) for the first time. Human blood cells were treated with alpha
      pinene (0 to 200 mg/L) for 24 and 48 h, and then cytotoxicity was detected by
      lactate dehydrogenase (LDH) release and (3-(4,5-dimethyl-thiazol-2-yl) 2,5
      diphenyltetrazolium bromide) (MTT) assay, while DNA damage was also analyzed by
      micronucleus (MN) assay, chromosomal aberration (CA) assay and 8-oxo-2
      deoxyguanosine (8-OH-dG). In addition, biochemical parameters (total antioxidant
      capacity (TAC) and total oxidative stress (TOS)) were examined to determine
      oxidative effects. The results of LDH and MTT assays showed that alpha-pinene (at
      200 mg/L) decreased cell viability. In our in vitro test systems, it was observed
      that alpha-pinene did not cause any statistically important changes in the rates
      of studied genotoxicity endpoints but dose-dependent alterations were observed in
      TAC and TOS levels. alpha-Pinene treatment caused increases in TAC levels (at 25
      and 50 mg/L) and decreases in TOS levels (only at 200 mg/L) on human lymphocytes.
      In conclusion, the findings of the present study confirm for the first time that
      alpha-pinene could be a significant source of natural antioxidant compound that
      may have beneficial health effects. 

PMID- 24081630
TI  - Heavy metals content, phytochemical composition, antimicrobial and insecticidal
      evaluation of Elaeagnus angustifolia.
AB  - Elaeagnus angustifolia was analyzed for determination of metals,
      phytoconstituents, bactericidal, fungicidal and insecticidal effects and to
      explore its chemical and biological potential. The root, branches, leaves, stem
      bark and root bark parts of E. angustifolia were found to contain iron, lead,
      copper, cadmium, zinc, chromium, nickel and cobalt in different concentrations.
      Crude extract of Elaeagnus angustifolia (Ea.Cr) was tested positive for the
      presence of alkaloids, flavonoids, saponins and tannins. Ea.Cr and its fractions,
      n-hexane (Ea.Hex), ethyl acetate (Ea.EtAc) and aqueous (Ea.Aq) showed
      bactericidal activity against Escherichia coli and Staphylococcus aureus, while
      against Pseudomonas aeruginosa only Ea.Hex and Ea.EtAc were effective. When
      tested for antifungal effect, Ea.Cr exhibited fungicidal action against
      Aspergillus fumagatus, Ea.EtAc and Ea.Aq against Aspergillus flavis and Ea.EtAc
      against Aspergillus niger. Ea.Hex was active against all three fungal strains.
      The chloroform fraction (Ea.CHCl3) was found inactive against the used microbes.
      Ea.Cr, Ea.Hex, Ea.CHCl3, Ea.EtAc and Ea.Aq caused mortality of Tribolium
      castaneum and Ephestia cautella insects observed after 24 and 48 h of treatment.
      These data indicate that E. angustifolia exhibits different heavy metals and
      compound groups. Methanolic extract of E. angustifolia and its various fractions
      possess antibacterial, antifungal and insecticidal activities, which elucidate
      medicinal application of the plant. 

PMID- 24081631
TI  - Protective effect of ascorbic acid and Ginkgo biloba against learning and memory
      deficits caused by fluoride.
AB  - Fluoride is present in the ground water, World Health Organization permitted
      level of fluoride in the ground water is 0.5 ppm. Tooth pastes, mouth washes, tea
      and sea fish are the sources of fluoride. Exposure to these multiple sources
      results in several adverse effects in addition to the fluorosis. The present
      study aimed to test the effect of vitamin C and Ginkgo biloba against the
      behavioural deficits caused by fluoride. Rats were divided into five groups with
      six animals in each group (n = 6). Control group received ordinary tap water with
      0.5 ppm of fluoride, the remaining groups received 100 ppm of fluoride for 30
      days prior to fluoride exposure. Two groups of animals received 100 mg/kg body
      weight of vitamin C and G. biloba for 15 days prior to fluoride exposure. After
      45 days, behavioural studies (T-Maze, passive avoidance) were conducted on the
      experimental animals. The results of the present study showed no behavioural
      deficits in the control group of animals however, the rats that received fluoride
      water exhibited impairment in their spatial learning and memory deficits. The
      deficits are not marked in the vitamin C and G. biloba groups. To conclude
      chronic exposure to high levels of fluoride causes severe impairment in the
      spatial learning and memory, these deficits can be ameliorated with the vitamin C
      and G. biloba.

PMID- 24081632
TI  - Studies on fate and toxicity of nanoalumina in male albino rats: Oxidative stress
      in the brain, liver and kidney.
AB  - The present work aimed to evaluate the oxidative stress of nanoalumina (aluminium
      oxide nanoparticles, Al2O3-NPs) with a diameter <13 nm (9.83 +/- 1.61 nm) as
      assessed by the perturbations in the enzymatic and non-enzymatic antioxidants as
      well as lipid peroxidation (LPO) in the brain, liver and kidney of male albino
      rats, after 2 days of single acute dose (3.9 or 6.4 or 8.5 g/kg) injection and a
      sublethal dose of 1.3 g/kg once in 2 days for a period of 28 days. According to
      two-way analysis of variance, superoxide dismutase (SOD), catalase (CAT) and
      glutathione peroxidase (GPx) activities as well as the levels of glutathione
      (GSH) and LPO were significantly affected by the injected doses, organs and their
      interactions. On the other hand, in sublethal experiments, these parameters were
      affected by the experimental periods, organs and their interactions. Regression
      analysis confirmed that the activities of SOD, CAT, GPx and GSH levels in the
      brain, liver and kidney were inversely proportional with the acute doses, the
      experimental periods, and aluminium accumulated in these tissues, whereas the
      levels of LPO exhibited a positive relationship. Correlation coefficient
      indicated that oxidative stress mainly depends on aluminium accumulated in the
      studied organs, followed by injected doses and the experimental periods. In
      comparison with the corresponding controls, the acute and sublethal doses of
      Al2O3-NPs caused significant inhibition of the brain, hepatic and renal SOD, CAT,
      GPx activities and a severe marked reduction in the concentrations of GSH that
      were associated with a significant elevation in the levels of malondialdehyde (an
      indicator of LPO). In conclusion, our data indicated that rats injected with
      nanoalumina suffered from the oxidative stresses that were dose and time
      dependent. In addition, Al2O3-NPs released into the biospheres could be
      potentiating a risk to the environment and causing hazard effects on living
      organisms, including mammals.

PMID- 24081633
TI  - Target hazard quotient evaluation of cadmium and lead in fish from Caspian Sea.
AB  - Heavy metals are being increasingly released into the natural waters from
      geological and anthropogenic sources. The distributions of several heavy metals
      such as cadmium (Cd) and lead (Pb) were investigated in muscle and liver of three
      different fish species seasonally collected from Caspian Sea (autumn 2011-summer
      2012). The concentrations of all metals were lower in flesh than those recorded
      in liver due to their physiological roles. The target hazard quotient (THQ) index
      for fish was calculated. Estimation of THQ calculations for the contaminated fish
      consumption was calculated to evaluate the effect of pollution on health. Total
      metal THQ values of Pb and Cd for adults were 0.05 and 0.04 in Anzali and
      Noshahr, respectively, and for children were 0.08 and 0.05 in Anzali and Noshahr,
      respectively.

PMID- 24081634
TI  - Physiological and biochemical changes after boldenone injection in adult rabbits.
AB  - Boldenone (BOL) is an androgenic steroid that improves the growth and food
      conversion in food-producing animals. In most countries worldwide, this anabolic
      steroid is forbidden for human uses and meat production as it was developed for
      veterinary use. Recently, BOL is used by bodybuilders in both off season and pre
      contest, where it is well known for increasing vascularity while preparing for a
      bodybuilding contest. The present study was designed to investigate the
      physiological and biochemical changes in rabbits after injection with the growth
      promoter BOL. A total of 32 adult New Zealand rabbits were divided into four
      groups, where the control group includes animals that were injected
      intramuscularly with olive oil and dissected after 3 weeks. The remaining three
      experimental groups included animals that received one, two and three
      intramuscular injections of 5 mg/kg body weight BOL, respectively, and were
      dissected after 3, 6 and 9 weeks, respectively. The animals from practice
      appeared healthy and did not show clinical signs of disease and none of the
      rabbits died during the experimental period. Serum total protein, globulin,
      alanine aminotransferase, asparate aminotransferase, urea, creatinine,
      testosterone, luteinizing hormone and follicle-stimulating hormone levels were
      significantly increased while serum direct bilirubin, albumin and
      albumin/globulin ratio were significantly decreased (p < 0.05) after one, two and
      three intramuscular injections of BOL as compared to their relative values in the
      control group. These findings explain the common phenomena in athletes and
      bodybuilders who suffer from infertility, renal and hepatic alterations following
      injection with some drugs as steroids (BOL) to build muscles.

PMID- 24081635
TI  - Ameliorating effect of pomegranate juice consumption on carbon tetrachloride
      induced sperm damages, lipid peroxidation, and testicular apoptosis.
AB  - The aim of this study was to investigate whether pomegranate juice (PJ)
      consumption has an ameliorating effect on carbon tetrachloride (CCl4)-induced
      sperm damages and testicular apoptosis associated with the oxidative stress in
      male rats. The study comprised of four groups (groups 1-4). Group 1 received
      olive oil + distilled water daily; group 2 was treated with 5 ml/kg PJ + olive
      oil daily; group 3 was treated with 0.25 ml/kg CCl4 dissolved in olive oil,
      weekly + distilled water daily; and group 4 received weekly CCl4 + daily PJ. All
      administrations were performed by gavage and maintained for 10 weeks. CCl4
      administration caused significant decreases in body and reproductive organ
      weights, sperm motility, concentration and testicular catalase activity,
      significant increases in malondialdehyde (MDA) level, and abnormal sperm rate and
      apoptotic index along with some histopathological damages when compared with the
      control group. However, significant ameliorations were observed in absolute
      weights of testis and epididymis, all sperm quality parameters, MDA level,
      apoptotic index, and testicular histopathological structure following the
      administration of CCl4 together with PJ when compared with group given CCl4 only.
      In conclusion, PJ consumption ameliorates the CCl4-induced damages in male
      reproductive organs and cells by decreasing the lipid peroxidation.

PMID- 24081636
TI  - Serum prolidase activity, oxidative stress, and antioxidant enzyme levels in
      patients with renal cell carcinoma.
AB  - OBJECTIVES: Prolidase is a member of the matrix metalloproteinase family. It
      plays a vital role in collagen turnover, matrix remodeling, and cell growth.
      Reactive oxygen species (ROS) have been implicated in the pathogenesis of various
      diseases, including cancers. Oxidative stress can cause tumor angiogenesis and
      may be carcinogenic. However, the relationship between antioxidant capacity and
      various cancers has been researched in several clinical trials. In our study, we
      aimed to identify serum prolidase activity, oxidative stress, and antioxidant
      enzyme levels in patients with renal tumors and to evaluate their relationships
      with each other. MATERIALS AND METHODS: A total of 37 male patients with renal
      cell cancer and with a mean age of 56.28 +/- 3.1 were included in the study. The
      control group comprising 36 male patients (mean age 56.31 +/- 2.9) was randomly
      selected among the volunteers. Serum samples for measurement of superoxide
      dismutase (SOD), glutathione peroxidase (GSHPx), glutathione-S-transferase (GST),
      malondialdehyde (MDA), glutathione (GSH), and prolidase levels were kept at -20
      degrees C until they were used. RESULTS: Serum prolidase activity and MDA levels
      were significantly higher in renal cancer patients than in controls (all, p <
      0.05), while SOD, GSHPx, and GST levels were significantly lower (p < 0.05).
      CONCLUSION: Our results indicate that increased prolidase seems to be related to
      increased oxidative stress along with decreased antioxidant levels in renal
      cancer.

PMID- 24081637
TI  - The protective effect of propylthiouracil against hepatotoxicity induced by
      chromium in adult mice.
AB  - Environmental and occupational exposure to chromium compounds, especially
      hexavalent chromium (Cr(VI)), is widely recognized as potentially hepatotoxic in
      humans and animals. Its toxicity is associated with overproduction of free
      radicals, which induces oxidative damage. This study focused on the possible
      protective effect of propylthiouracil (PTU) against potassium dichromate
      (K2Cr2O7). Female mice were divided into four groups (groups I-IV) with seven
      animals in each group. Group I served as a control, which received tap water;
      group II received K2Cr2O7 alone (75 mg kg(-1) body weight (b.w.)) via drinking
      water; group III received both K2Cr2O7 via drinking water and PTU by
      intramuscular injection at a dose 2.5 mg/100 g(-1) b.w. twice a week, and group
      IV received PTU alone twice a week for 30 days. Exposure of mice to Cr promoted
      oxidative stress with an increase in malondialdehyde, protein carbonyl, and
      advanced oxidation protein product levels. Nonenzymatic antioxidants such as
      glutathione, nonprotein thiol, vitamin C levels and enzymatic antioxidant
      activities such as glutathione peroxidase and superoxide dismutase were
      decreased, while catalase activity was increased. Biomarkers of liver injury such
      as aspartate and alanine transaminases, lactate dehydrogenase activities,
      bilirubin, albumin, and glucose levels were increased, while triglyceride and
      cholesterol levels decreased. Coadministration of PTU restored the above
      mentioned parameters to near-normal values. The histological findings confirmed
      the biochemical results.

PMID- 24081638
TI  - The effects of intravenous immunoglobulin on cerebral ischemia in rats: An
      experimental study.
AB  - Stroke is one of the major reasons of death in the United States and related to
      adult disability. Despite aggressive research, the treatment approaches of stroke
      still remains a major clinical problem. Intravenous immunoglobulin (IVIg) is a
      polyspecific Ig G preparation obtained from plasma of several thousand healthy
      people (donors). IVIg is an important treatment approach and used for several
      disorders. The aim of this study was to investigate the potentially beneficial
      effects of IVIg therapy in experimentally induced ischemia in middle cerebral
      artery occlusion (MCAo) models of rats. A total of 30 adult male Sprague Dawley
      rats were used. The rats were divided into two equal groups, each consisting of
      15 randomly selected rats: control group (n = 15) and IVIg group (n = 15).
      Intraluminal filament method was used for establishment of cerebral ischemia.
      Intraluminal filament was withdrawn after 2 h of MCAo and reperfusion started
      again and passed to therapeutic stages for all the groups. Physiologic saline
      solution of 0.5 ml/kg was administered to the control group and 400 mg/kg IVIg
      was given to the IVIg group rats intravenously. In neurological evaluation, the
      worst score was determined as 3 and the best score as 0. After routine process,
      the brain tissue was prepared histopathological investigation. The IVIg group
      showed significantly better recovery with respect to the control group by
      neurological examination. The observation of specimens obtained from IVIg groups
      showed that findings correlate with grade 1 and -2 histopathologically.
      Nevertheless, ischemic amendments were observed to comply with grade 3 in
      ischemic areas in control group. IVIg therapy can be used in the treatment of
      ischemic stroke patients.

PMID- 24081639
TI  - In silico interaction of methyl isocyanate with immune protein responsible for
      Mycobacterium tuberculosis infection using molecular docking.
AB  - This article reports in silico analysis of methyl isocyanate (MIC) on different
      key immune proteins against Mycobacterium tuberculosis. The analysis shows that
      MIC is released in the Bhopal gas tragedy in 1984, which is highly toxic and
      extremely hazardous to human health. In this study, we have selected immune
      proteins to perform molecular docking with the help of Autodock 4.0. Results show
      that the CD40 ligand and alpha5beta1 integrin have higher inhibition compared to
      plasminogen activator urokinase, human glutathione synthetase, mitogen-activated
      protein kinase (P38 MAPK 14), surfactant protein-B, -D (SP-D), and pulmonary SP
      D. MIC interacted with His-125, Try-146 residue of CD40 ligand and Ala-149, and
      Arg-152 residue of alpha5beta1 integrin and affects the proteins functioning by
      binding on their active sites. These inhibitory conformations were energetically
      and statistically favored and supported the evidence from wet laboratory
      experiments reported in the literature. We can conclude that MIC directly or
      indirectly affects these proteins, which shows that survivals of the disaster
      suffer from the diseases like tuberculosis infection and lung cancer. 

PMID- 24081640
TI  - Comparative toxicity of Paraquat herbicide and some plant extracts in Lymnaea
      natalensis snails.
AB  - Paraquat has been shown to be a highly toxic compound for humans and animals, and
      many cases of acute poisoning and death have been reported over the past few
      decades. The present study was undertaken to evaluate comprehensively herbicides
      (Paraquat) and some plant extracts to biochemical aspects of Lymnaea natalensis
      snails. It was found that the exposure of L. natalensis to Paraquat and plant
      extracts led to a significant reduction in the infectivity of Fasciola gigantica
      miracidia to the snail. The glucose level in hemolymph of exposed snails was
      elevated, while the glycogen showed a decrease in soft tissues when compared with
      the control group. In addition, the activity level of some enzymes representing
      glycolytic enzymes as hexokinase (HK), pyruvate kinase (PK), phosphofructokinase
      (PFK), lactate dehydrogenase (LDH), and glucose phosphate isomerase (GPI) in
      snail's tissues were reduced in response to the treatment. It was concluded that
      the pollution of the aquatic environment by herbicide would adversely affect the
      metabolism of the L. natalensis snails. Snails treated with Agave attenuate, Ammi
      visnaga, and Canna iridiflora plant had less toxic effect compared to snails
      treated with Paraquat. 

PMID- 24081641
TI  - Less-established risk factors are common in Asian Americans with hepatitis C
      virus: a case-controlled study.
AB  - BACKGROUND AND AIMS: The Centers for Disease Control and Prevention recommend
      screening for hepatitis C virus (HCV) in patients with injection drug use, blood
      transfusion before 1992, stigmata of liver disease, or born between 1945 and
      1965. The purpose of this study was to examine risk factors for HCV acquisition
      in Asian Americans. METHODS: This was a case-controlled study, with 471
      consecutive patients testing positive for anti-HCV between January 2001 and
      December 2008. Controls included 471 patients with negative HCV matched at a one
      to-one ratio for sex, age (+/-5 years), and ethnicity. RESULTS: For Asian
      patients, the most common risk factors were blood transfusion and acupuncture or
      exposure to dirty needles (27 and 20 %, respectively). On multiple logistic
      regression, potential predictors for a positive anti-HCV test in Asians were
      acupuncture or exposure to dirty needles (OR = 12.9, P < 0.0001), body tattoo (OR
      = 12.0, P = 0.001), and history of blood transfusion (OR = 5.7, P < 0.0001).
      DISCUSSION: Acupuncture and exposure to dirty needles are independent risk
      factors of HCV infection. Asians coming from endemic areas should be screened for
      HCV even when commonly-known risk factors for Western patients are not present.

PMID- 24081642
TI  - Surgeon's volume is not associated with complication outcome after laparoscopic
      cholecystectomy.
AB  - AIM: Complication rates after laparoscopic cholecystectomy vary but are still
      reported to be up to 17 %. Identifying risk factors for an adverse complication
      outcome could help to reduce morbidity after laparoscopic cholecystectomy. Our
      aim was to analyze whether surgeon volume is a vital issue for complication
      outcome. METHODS: All complications-minor, major, local and general-were reviewed
      in a single institution between January 2004 and December 2008 and recorded in a
      database. Patient's variables, disease related variables and surgeon's variables
      were noted. The role of surgeon's individual volume per year was analyzed. A
      stepwise logistic regression model was used. RESULTS: A total of 942 patients
      were analyzed, among which 70 (7 %) patients with acute cholecystitis and 52 (6
      %) patients with delayed surgery for acute cholecystitis. Preoperative endoscopic
      retrograde cholangiography (ERC) had been performed in 142 (15 %) patients.
      Complication rates did not differ significantly for surgeon's individual volume
      (<=10 vs. >10 LC/year, 5.2 vs. 8.2 %, p = 0.203) nor for specialization
      (laparoscopic vs. non-laparoscopic; 9.2 vs. 6.4 %, p = 0.085) and experience
      (specialty registration <=5 vs. >5 years; 5.1 vs. 8.7 %, p = 0.069). The only
      significant predictors for complications were acute surgery (OR 3.9, 95 % CI 1.8
      8.7, p = 0.001) and a history preceding laparoscopic cholecystectomy (LC) (ERC
      and delayed surgery for cholecystitis) (OR 8.1, 95 % CI 4.5-14.6: p <0.001).
      CONCLUSION: Complications after LC were not significantly associated with a
      surgeon's individual volume, but most prominently determined by the type of
      biliary disease.

PMID- 24081643
TI  - The common dementias: a pictorial review.
AB  - Imaging plays an important role in the diagnosis and management of dementia. This
      review covers the imaging features of the most common dementing illnesses:
      Alzheimer's disease (AD), vascular dementia (VaD), dementia with Lewy bodies
      (DLB) and frontotemporal lobar degeneration (FTLD). It describes typical findings
      on structural neuroimaging and discusses functional and molecular imaging
      techniques such as FDG PET, amyloid PET, magnetic resonance (MR) perfusion
      imaging, diffusion tensor imaging (DTI) and functional MR imaging (fMRI). 

PMID- 24081644
TI  - Diffusion-weighted imaging with acquisition of three b-values for response
      evaluation of neuroendocrine liver metastases undergoing selective internal
      radiotherapy.
AB  - OBJECTIVES: To evaluate diffusion-weighted MRI with acquisition of three b-values
      and calculation of fractioned ADCs for response evaluation of neuroendocrine
      liver metastases undergoing selective internal radiotherapy (SIRT). METHODS: Ten
      consecutive patients with neuroendocrine liver metastases underwent MRI before
      and following SIRT. Diffusion-weighted imaging included acquisition of the b
      values 0, 50 and 800 s/mm(2) and calculation of ADC(50,800), ADC(0,50) and
      ADC(0,800) maps. According to therapy response, lesions were categorised into
      group A [>=20% reduction of the longest diameter (LD) in comparison to baseline
      MRI] and group B (<20% reduction of the LD). RESULTS: Twelve out of 31 metastases
      were categorised as group A and 19 out of 31 metastases were categorised as group
      B. Pretherapeutic values of ADC(0,800) and ADC(50,800) did not differ
      significantly between the two groups; however, ADC(0,50) was 32% lower in group A
      (P = 0.049). ADC(0,800) and ADC(50,800) increased significantly after therapy in
      both groups, however, group differences were not statistically significant.
      Conversely, the increase in ADC(0,50) was about a factor of 7 larger in group A
      than in group B (P = 0.023). CONCLUSIONS: Our study showed that the ADC(0,50) is
      a promising biomarker for response assessment of neuroendocrine liver metastases
      following SIRT. KEY POINTS: * Diffusion-weighted MRI offers new information about
      neuroendocrine hepatic metastases. * Evaluation of perfusion and diffusion
      components requires fractioned apparent diffusion coefficients (ADCs). *
      Perfusion effects represented by ADC (0.50) can be observed in neuroendocrine
      metastases. * Pretherapeutic ADC (0.50) was significantly lower in metastases
      with a response >=20%. * Such biomarkers may help evaluate liver metastases in
      patients undergoing therapy.

PMID- 24081645
TI  - Low-tube-voltage (80 kVp) CT aortography using 320-row volume CT with adaptive
      iterative reconstruction: lower contrast medium and radiation dose.
AB  - OBJECTIVES: To evaluate CT aortography at reduced tube voltage and contrast
      medium dose while maintaining image quality through iterative reconstruction
      (IR). METHODS: The Institutional Review Board approved a prospective study of 48
      patients who underwent follow-up CT aortography. We performed intra-individual
      comparisons of arterial phase images using 120 kVp (standard tube voltage) and 80
      kVp (low tube voltage). Low-tube-voltage imaging was performed on a 320-detector
      CT with IR following injection of 40 ml of contrast medium. We assessed aortic
      attenuation, aortic attenuation gradient, image noise, contrast-to-noise ratio
      (CNR), volume CT dose index (CTDIvol), and figure of merit (FOM) of image noise
      and CNR. Two readers assessed images for diagnostic quality, image noise, and
      artefacts. RESULTS: The low-tube-voltage protocol showed 23-31% higher mean
      aortic attenuation and image noise (both P < 0.01) than the standard-tube-voltage
      protocol, but no significant difference in the CNR and aortic attenuation
      gradients. The low-tube-voltage protocol showed a 48% reduction in CTDIvol and an
      80% increase in FOM of CNR. Subjective diagnostic quality was similar for both
      protocols, but low-tube-voltage images showed greater image noise (P = 0.01).
      CONCLUSIONS: Application of IR to an 80-kVp CT aortography protocol allows
      radiation dose and contrast medium reduction without affecting image quality. KEY
      POINTS: * CT aortography at 80 kVp allows a significant reduction in radiation
      dose. * Addition of iterative reconstruction reduces image noise and improves
      image quality. * The injected contrast medium dose can be substantially reduced
      at 80 kVp. * Aortic enhancement is uniform despite a reduced volume of contrast
      medium.

PMID- 24081646
TI  - In vivo sodium (23Na) imaging of the human kidneys at 7 T: preliminary results.
AB  - OBJECTIVE: To evaluate the feasibility of in vivo (23)Na imaging of the
      corticomedullary (23)Na gradient and to measure (23)Na transverse relaxation
      times (T2*) in human kidneys. METHODS: In this prospective, IRB-approved study,
      eight healthy volunteers (4 female, 4 male; mean age 29.4 +/- 3.6 years) were
      examined on a 7-T whole-body MR system using a (23)Na-only spine-array coil. For
      morphological (23)Na-MRI, a 3D gradient echo (GRE) sequence with a variable echo
      time scheme (vTE) was used. T2* times were calculated using a multiecho 3D vTE
      GRE approach. (23)Na signal-to-noise ratios (SNR) were given on a pixel-by-pixel
      basis for a 20-mm section from the cortex in the direction of the medulla. T2*
      maps were calculated by fitting the (23)Na signal decay monoexponentially on a
      pixel-by-pixel basis, using least squares fit. RESULTS: Mean corticomedullary
      (23)Na-SNR increased from the cortex (32.2 +/- 5.6) towards the medulla (85.7 +/-
      16.0). The SNR increase ranged interindividually from 57.2% to 66.3%. Mean (23)Na
      T2* relaxation times differed statistically significantly (P < 0.001) between the
      cortex (17.9 +/- 0.8 ms) and medulla (20.6 +/- 1.0 ms). CONCLUSION: The aim of
      this study was to evaluate the feasibility of in vivo (23)Na MRI of the
      corticomedullary (23)Na gradient and to measure the (23)Na T2* relaxation times
      of human kidneys at 7 T. KEY POINTS: * High field MR offers new insights into
      renal anatomy and physiology. * (23) Na MRI of healthy human kidneys is feasible
      at ultra-high field. * Renal (23) Na concentration increases from the cortex in
      the medullary pyramid direction. * In vivo measurements of renal (23) Na-T2*
      times are demonstrated at 7.0 T.

PMID- 24081647
TI  - Urinary stone detection and characterisation with dual-energy CT urography after
      furosemide intravenous injection: preliminary results.
AB  - OBJECTIVES: To investigate the added advantage of IV furosemide injection and the
      subsequent urine dilution in the detection of urinary calculi in the excretory
      phase of dual-source dual-energy (DE) computed tomography (CT) urography, and to
      investigate the feasibility of characterising the calculi through diluted urine.
      METHODS: Twenty-three urinary calculi were detected in 116 patients who underwent
      DECT urography for macroscopic haematuria with a split bolus two- or three
      acquisition protocol, including a true unenhanced series and at least a mixed
      nephrographic excretory phase. Virtual unenhanced images were reconstructed from
      contrast-enhanced DE data. Calculi were recorded on all series and characterised
      based on their X-ray absorption characteristics at 100 kVp and 140 kVp in both
      true unenhanced and nephrographic excretory phase series. RESULTS: All calculi
      with a diameter more than 2 mm were detected in the virtual unenhanced phase and
      in the nephrographic excretory phase. Thirteen of these calculi could be
      characterised in the true unenhanced phase and in the mixed nephrographic
      excretory phase. The results were strictly identical for both phases, six of them
      being recognised as non-uric acid calculi and seven as uric acid calculi.
      CONCLUSIONS: Mixed nephrographic excretory phase DECT after furosemide
      administration allows both detection and characterisation of clinically
      significant calculi, through the diluted urine. KEY POINTS: * Urinary tract
      stones can be detected on excretory phase through diluted urine. * Urinary tract
      stone characterisation with dual-energy CT (DECT) is possible through diluted
      urine. * A dual energy split-bolus CT urography simultaneously enables urinary
      stone detection and characterisation.

PMID- 24081648
TI  - Potential role of shear-wave ultrasound elastography for the differential
      diagnosis of breast non-mass lesions: preliminary report.
AB  - OBJECTIVES: To report our preliminary experience with shear-wave elastography
      (SWE) for non-mass lesions (NMLs) in the breast and suggest a potential ancillary
      role of SWE for BI-RADS Category 4a NMLs in reducing the number of unnecessary
      benign biopsies. METHODS: A total of 310 breast lesions in 286 consecutive women
      who had been scheduled for US-guided automated gun biopsy or vacuum-assisted
      biopsy between June and December 2012 were initially included in this study.
      Finally, 33 women with 34 breast lesions classified as NMLs constituted our study
      population. Diagnostic performances of each quantitative SWE parameter were
      calculated. Histological diagnosis was used as a reference standard. RESULTS:
      Among the 34 breast NMLs, 22 (65%) were benign and 12 (35%) were malignant. Emean
      value with cut-off set at 41.6 kPa had the highest Az value 0.788 (95% CI, 0.625
      0.951), showing sensitivity of 83.3% and specificity of 68.2%. By applying an
      Emean value of 41.6 kPa or less as a criterion for downgrading soft BI-RADS
      category 4a NMLs to category 3 NMLs, 15 unnecessary biopsies could have been
      eliminated from the 19 BI-RADS category 4a lesions (79%). CONCLUSIONS: SWE
      features could increase positive predictive values and reduce unnecessary benign
      biopsies of category 4a NMLs. KEY POINTS: * Ultrasound elastography is
      increasingly used to assess the stiffness of breast lesions * Shear-wave
      elastography provides useful information about non-mass breast lesions * Shear
      wave elastography may render some biopsies of non-mass breast lesions
      unnecessary.

PMID- 24081649
TI  - Comparison of dual-energy CT-derived iodine content and iodine overlay of normal,
      inflammatory and metastatic squamous cell carcinoma cervical lymph nodes.
AB  - OBJECTIVES: To evaluate whether dual-energy computed tomography (DECT)-derived
      iodine content and iodine overlay could differentiate between normal,
      inflammatory and metastatic squamous cell carcinoma (SCC) cervical lymph nodes.
      METHODS: This study was approved by the institutional review board. Sixteen
      patients with normal lymph nodes, 20 patients with enlarged nodes draining deep
      cervical inflammations and 23 patients with pathologically proved metastatic SCC
      nodes who underwent contrast enhanced DECT were retrospectively identified.
      Iodine content and overlay of 36 normal, 43 inflammatory and 52 metastatic lymph
      nodes were calculated using circular regions of interest and compared among the
      three groups. A receiver operating characteristic (ROC) curve was used to
      determine the sensitivity and specificity of iodine content and overlay for
      diagnosis of metastatic nodes. RESULTS: Iodine content (mg/ml) was significantly
      lower for metastatic lymph nodes (2.34 +/- 0.45) than for normal (2.86 +/- 0.37)
      and inflammatory (3.53 +/- 0.56) lymph nodes, P < 0.0001. Iodine overlay (HU) was
      also significantly lower for metastatic lymph nodes (47 +/- 11.6) than normal
      (57.4 +/- 8.2) and inflammatory nodes (69.3 +/- 11.5), P < 0.0001. The areas
      under the ROC curve for iodine content and iodine overlay were 0.923 and 0.896.
      CONCLUSIONS: DECT-derived iodine content and overlay differ significantly among
      normal, inflammatory and metastatic SCC cervical lymph nodes. KEY POINTS: *
      Derived iodine content can be calculated from contrast-enhanced dual-energy CT. *
      Derived iodine content and iodine overlay could help characterise cervical lymph
      nodes. * Iodine parameters were significantly lower in metastatic lymph nodes
      than normal/inflammatory lymph nodes. * Iodine content appears more sensitive
      than iodine overlay for lymph node characterisation.

PMID- 24081650
TI  - Small scale membrane mechanics.
AB  - Large scale changes to lipid bilayer shapes are well represented by the Helfrich
      model. However, there are membrane processes that take place at smaller length
      scales that this model cannot address. In this work, we present a one-dimensional
      continuum model that captures the mechanics of the lipid bilayer membrane at the
      length scale of the lipids themselves. The model is developed using the Cosserat
      theory of surfaces with lipid orientation, or 'tilt', as the fundamental degree
      of freedom. The Helfrich model can be recovered as a special case when the
      curvatures are small and the lipid tilt is everywhere zero. We use the tilt model
      to study local membrane deformations in response to a protein inclusion.
      Parameter estimates and boundary conditions are obtained from a coarse-grained
      molecular model using dissipative particle dynamics (DPD) to capture the same
      phenomenon. The continuum model is able to reproduce the membrane bending,
      stretch and lipid tilt as seen in the DPD model. The lipid tilt angle relaxes to
      the bulk tilt angle within 5-6 nm from the protein inclusion. Importantly, for
      large tilt gradients induced by the proteins, the tilt energy contribution is
      larger than the bending energy contribution. Thus, the continuum model of tilt
      accurately captures behaviors at length scales shorter than the membrane
      thickness.

PMID- 24081652
TI  - [Desmoid tumor of the nasopharynx].

PMID- 24081651
TI  - Nfasc155H and MAG are specifically susceptible to detergent extraction in the
      absence of the myelin sphingolipid sulfatide.
AB  - Mice incapable of synthesizing the myelin lipid sulfatide form paranodes that
      deteriorate with age. Similar instability also occurs in mice that lack
      contactin, contactin-associated protein or neurofascin155 (Nfasc155), the
      proteins that cluster in the paranode and form the junctional complex that
      mediates myelin-axon adhesion. In contrast to these proteins, sulfatide has not
      been shown to be enriched in the paranode nor has a sulfatide paranodal binding
      partner been identified; thus, it remains unclear how the absence of sulfatide
      results in compromised paranode integrity. Using an in situ extraction procedure,
      it has been reported that the absence of the myelin sphingolipids,
      galactocerebroside and sulfatide, increased the susceptibility of Nfasc155 to
      detergent extraction. Here, employing a similar approach, we demonstrate that in
      the presence of galactocerebroside but in the absence of sulfatide Nfasc155 is
      susceptible to detergent extraction. Furthermore, we use this in situ approach to
      show that stable association of myelin-associated glycoprotein (MAG) with the
      myelin membrane is sulfatide dependent while the membrane associations of
      myelin/oligodendrocyte glycoprotein, myelin basic protein and cyclic nucleotide
      phosphodiesterase are sulfatide independent. These findings indicate that myelin
      proteins maintain their membrane associations by different mechanisms. Moreover,
      the myelin proteins that cluster in the paranode and require sulfatide mediate
      myelin-axon adhesion. Additionally, the apparent dependency on sulfatide for
      maintaining Nfasc155 and MAG associations is intriguing since the fatty acid
      composition of sulfatide is altered and paranodal ultrastructure is compromised
      in multiple sclerosis. Thus, our findings present a potential link between
      sulfatide perturbation and myelin deterioration in multiple sclerosis. 

PMID- 24081653
TI  - [Speech perception in noise with the "wuerzburg speech test for children"].
AB  - BACKGROUND: Patients with hearing loss complain of a reduced speech perception in
      noise. For school children and adults there are several standardized audiometric
      tests available to measure the outcome in background noise like the HSM-Test,
      OlSa or OlKiSa. However, for kindergarden and preschool children a comparable
      speech perception test in noise does not exist. The aim of this study was to
      evaluate and standardize the recently developed "wuerzburg speech test for
      children" in noise. MATERIALS AND METHODS: 24 children aged 5-9 years with
      bilateral normal hearing were included. They have been tested with the test IV of
      the "wuerzburg speech test for children" in noise. This test consists of 3 lists,
      each with 20 two-syllable words. For the background noise, a 32 time delayed
      interference of the speech items were used. RESULTS: The speech perception
      threshold (SRT) at 60 dB (SPL) depending on the signal to noise ratio (SNR) was
      measured for each child. The overall averaged SNR was -8.3 dB. Furthermore a
      small, non-significant influence by the age of the children to the test results
      was seen. CONCLUSION: The "wuerzburg speech test for children" is suitable to
      measure the individual speech perception in noise. It is appropriate for
      kindergarden, preschool and school children. The test material consists of the
      uptodate vocabulary of children. The average SRT was -8.3 dB SNR, which is
      comparable with the published literature.

PMID- 24081654
TI  - [Postoperative complications after surgery for vestibular schwannoma via the MCF
      approach].
AB  - BACKGROUND: The aim of this study was to analyze complications after surgery for
      vestibular schwannoma (VS) via the middle cranial fossa (MCF) approach. PATIENTS
      AND METHODS: 112 consecutive patients have been operated on via MCF approach in
      our department between October 2005 and March 2011. Postoperative complications
      have been registered during hospital stay as well as during outpatient follow-up.
      RESULTS: 25 complications occurred in 20 patients, most common was a CSF leak
      (12%). In 9 cases leakage stopped after conservative management. 3 patients
      needed lumbar drainage and 1 patient had to undergo revision-surgery. 6 patients
      suffered from hemorrhage: 2 cerebellar bleedings, 1 subdural hematoma, 2
      hematomas of the scalp and 1 bleeding of the sutured wound. All bleedings except
      the case with subdural hematoma could be managed conservatively. Furthermore, one
      case of meningitis and one transient ischemic attack were observed. 3 patients
      suffered from a deep venous thrombosis which led to a lethal pulmonary embolism
      in one case. CONCLUSIONS: Surgery for VS via the MCF approach is an established
      method with satisfying functional results and a low -complication rate. CSF leak
      is a common complication (12%) that can be managed conservatively in most of the
      cases. Severe complications that may lead to revision surgery are rare (2%).
      Persisting sequels of these complications occur in less than 1% of the cases.

PMID- 24081655
TI  - Telaprevir-induced, but not pegylated interferon-associated, retinopathy as a
      noteworthy adverse effect during triple antiviral therapy in patients with
      chronic hepatitis C.
AB  - BACKGROUND: The significance of retinopathy during triple therapy with telaprevir
      is uncertain. METHODS: Ophthalmologic examination was done prospectively before
      and every month during the therapy in 95 CHC patients. RESULTS: Retinopathy was
      found in 46 (48.4 %), and the specialists recommended discontinuation of the
      therapy in 9 (9.5 %). Such lesions may develop as adverse effects by telaprevir,
      since the lesions disappeared following discontinuation of telaprevir in a 65
      year-old man, in whom both pegylated-interferon (Peg-IFN) and ribavirin were
      continued, and reappeared when he took telaprevir again by his decision.
      Multivariate analysis revealed that interleukin 28B single-nucleotide
      polymorphism (IL28B SNP) and anemia development during the therapy were
      independent factors associating retinopathy. CONCLUSION: Ophthalmologic
      examinations should be done carefully during triple therapy, since the incidence
      was higher than that in previous Peg-IFN therapy, and lesions may develop as
      adverse effects by telaprevir, but not by Peg-IFN, especially in those showing
      preferable IL28B SNPs allele and/or anemia during the therapy.

PMID- 24081656
TI  - Prospective cohort study comparing intravenous busulfan to total body irradiation
      in hematopoietic cell transplantation.
AB  - We conducted a prospective cohort study testing the noninferiority of survival of
      ablative intravenous busulfan (IV-BU) vs ablative total body irradiation (TBI)
      based regimens in myeloid malignancies. A total of 1483 patients undergoing
      transplantation for myeloid malignancies (IV-BU, N = 1025; TBI, N = 458) were
      enrolled. Cohorts were similar with respect to age, gender, race, performance
      score, disease, and disease stage at transplantation. Most patients had acute
      myeloid leukemia (68% IV-BU, 78% TBI). Grafts were primarily peripheral blood
      (77%) from HLA-matched siblings (40%) or well-matched unrelated donors (48%). Two
      year probabilities of survival (95% confidence interval [CI]), were 56% (95% CI,
      53%-60%) and 48% (95% CI, 43%-54%, P = .019) for IV-BU (relative risk, 0.82; 95%
      CI, 0.68-0.98, P = .03) and TBI, respectively. Corresponding incidences of
      transplant-related mortality (TRM) were 18% (95% CI, 16%-21%) and 19% (95% CI,
      15%-23%, P = .75) and disease progression were 34% (95% CI, 31%-37%) and 39% (95%
      CI, 34%-44%, P = .08). The incidence of hepatic veno-occlusive disease (VOD) was
      5% for IV-BU and 1% with TBI (P < .001). There were no differences in progression
      free survival and graft-versus-host disease. Compared with TBI, IV-BU resulted in
      superior survival with no increased risk for relapse or TRM. These results
      support the use of myeloablative IV-BU vs TBI-based conditioning regimens for
      treatment of myeloid malignancies. 

PMID- 24081658
TI  - Cell-intrinsic regulation of murine dendritic cell function and survival by
      prereceptor amplification of glucocorticoid.
AB  - Although the inhibitory effects of therapeutic glucocorticoids (GCs) on dendritic
      cells (DCs) are well established, the roles of endogenous GCs in DC homeostasis
      are less clear. A critical element regulating endogenous GC concentrations
      involves local conversion of inactive substrates to active 11
      hydroxyglucocorticoids, a reduction reaction catalyzed within the endoplasmic
      reticulum by an enzyme complex containing 11beta-hydroxysteroid dehydrogenase
      type 1 (11betaHSD1) and hexose-6-phosphate dehydrogenase (H6PDH). In this study,
      we found that this GC amplification pathway operates both constitutively and
      maximally in steady state murine DC populations and is unaffected by additional
      inflammatory stimuli. Under physiologic conditions, 11betaHSD1-H6PDH increases
      the sensitivity of plasmacytoid DCs (pDCs) to GC-induced apoptosis and restricts
      the survival of this population through a cell-intrinsic mechanism. Upon CpG
      activation, the effects of enzyme activity are overridden, with pDCs becoming
      resistant to GCs and fully competent to release type I interferon. CD8alpha(+)
      DCs are also highly proficient in amplifying GC levels, leading to impaired
      maturation following toll-like receptor-mediated signaling. Indeed, pharmacologic
      inhibition of 11betaHSD1 synergized with CpG to enhance specific T-cell responses
      following vaccination targeted to CD8alpha(+) DCs. In conclusion, amplification
      of endogenous GCs is a critical cell-autonomous mechanism for regulating the
      survival and functions of DCs in vivo. 

PMID- 24081657
TI  - G protein-dependent basal and evoked endothelial cell vWF secretion.
AB  - von Willebrand factor (vWF) secretion by endothelial cells (ECs) is essential for
      hemostasis and thrombosis; however, the molecular mechanisms are poorly
      understood. Interestingly, we observed increased bleeding in EC-Galpha13(-/
      );Galpha12(-/-) mice that could be normalized by infusion of human vWF. Blood
      from Galpha12(-/-) mice exhibited significantly reduced vWF levels but normal vWF
      multimers and impaired laser-induced thrombus formation, indicating that Galpha12
      plays a prominent role in EC vWF secretion required for hemostasis and
      thrombosis. In isolated buffer-perfused mouse lungs, basal vWF levels were
      significantly reduced in Galpha12(-/-), whereas thrombin-induced vWF secretion
      was defective in both EC-Galphaq(-/-);Galpha11(-/-) and Galpha12(-/-) mice. Using
      siRNA in cultured human umbilical vein ECs and human pulmonary artery ECs,
      depletion of Galpha12 and soluble N-ethylmaleimide-sensitive-fusion factor
      attachment protein alpha (alpha-SNAP), but not Galpha13, inhibited both basal and
      thrombin-induced vWF secretion, whereas overexpression of activated Galpha12
      promoted vWF secretion. In Galphaq, p115 RhoGEF, and RhoA-depleted human
      umbilical vein ECs, thrombin-induced vWF secretion was reduced by 40%, whereas
      basal secretion was unchanged. Finally, in vitro binding assays revealed that
      Galpha12 N-terminal residues 10-15 mediated the binding of Galpha12 to alpha
      SNAP, and an engineered alpha-SNAP binding-domain minigene peptide blocked basal
      and evoked vWF secretion. Discovery of obligatory and complementary roles of
      Galpha12 and Galphaq/11 in basal vs evoked EC vWF secretion may provide promising
      new therapeutic strategies for treatment of thrombotic disease. 

PMID- 24081659
TI  - The CSF3R T618I mutation causes a lethal neutrophilic neoplasia in mice that is
      responsive to therapeutic JAK inhibition.
AB  - We have recently identified targetable mutations in CSF3R (GCSFR) in 60% of
      chronic neutrophilic leukemia (CNL) and atypical (BCR-ABL-negative) chronic
      myeloid leukemia (aCML) patients. Here we demonstrate that the most prevalent,
      activating mutation, CSF3R T618I, is sufficient to drive a lethal
      myeloproliferative disorder in a murine bone marrow transplantation model. Mice
      transplanted with CSF3R T618I-expressing hematopoietic cells developed a
      myeloproliferative disorder characterized by overproduction of granulocytes and
      granulocytic infiltration of the spleen and liver, which was uniformly fatal.
      Treatment with the JAK1/2 inhibitor ruxolitinib lowered the white blood count and
      reduced spleen weight. This demonstrates that activating mutations in CSF3R are
      sufficient to drive a myeloproliferative disorder resembling aCML and CNL that is
      sensitive to pharmacologic JAK inhibition. This murine model is an excellent tool
      for the further study of neutrophilic myeloproliferative neoplasms and implicates
      the clinical use of JAK inhibitors for this disease. 

PMID- 24081660
TI  - Platelet endothelial cell adhesion molecule 1 deficiency misguides venous
      thrombus resolution.
AB  - Platelet endothelial cell adhesion molecule 1 (PECAM-1) is involved in leukocyte
      migration and angiogenesis, which are key components of venous thrombus
      resolution. This study investigated the effect of PECAM-1 deficiency on thrombus
      resolution in FVB/n mice and the extent to which levels of soluble PECAM-1
      (sPECAM-1) correlate with delayed thrombus resolution in humans after acute
      symptomatic deep vein thrombosis (DVT). In a mouse stagnant flow venous
      thrombosis model Pecam-1(-/-) thrombi were larger, persisted for longer periods
      of time, and displayed attenuated macrophage invasion and decreased vessel
      formation in the presence of increased fibrosis. In humans, higher levels of
      truncated plasma sPECAM-1 possibly cleaved from cell surfaces, were found in
      patients with delayed thrombus resolution (assessed via duplex-based thrombus
      scoring) relative to those whose thrombi resolved (median, 25th/75th percentile):
      92.5 (87.7/103.4) ng/mL vs 71.5 (51.1/81.0) ng/mL; P < .001. Furthermore,
      unresolved human deep vein thrombus specimens stained positively with antibodies
      specific for the extracellular, but not the cytoplasmic domain of PECAM-1,
      consistent with accumulation of cleaved PECAM-1. Our data suggest a regulatory
      role of PECAM-1 in venous thrombus resolution and suggest a predictive value of
      sPECAM-1 for postthrombotic syndrome (PTS) after acute DVT. 

PMID- 24081661
TI  - Elevated CXCL1 expression in gp130-deficient endothelial cells impairs neutrophil
      migration in mice.
AB  - Neutrophils emigrate from venules to sites of infection or injury in response to
      chemotactic gradients. How these gradients form is not well understood. Some IL-6
      family cytokines stimulate endothelial cells to express adhesion molecules and
      chemokines that recruit leukocytes. Receptors for these cytokines share the
      signaling subunit gp130. We studied knockout mice lacking gp130 in endothelial
      cells. Unexpectedly, gp130-deficient endothelial cells constitutively expressed
      more CXCL1 in vivo and in vitro, and even more upon stimulation with tumor
      necrosis factor-alpha. Mobilization of this increased CXCL1 from intracellular
      stores to the venular surface triggered beta2 integrin-dependent arrest of
      neutrophils rolling on selectins but impaired intraluminal crawling and
      transendothelial migration. Superfusing CXCL1 over venules promoted neutrophil
      migration only after intravenously injecting mAb to CXCL1 to diminish its
      intravascular function or heparinase to release CXCL1 from endothelial
      proteoglycans. Remarkably, mice lacking gp130 in endothelial cells had impaired
      histamine-induced venular permeability, which was restored by injecting anti-P
      selectin mAb to prevent neutrophil rolling and arrest. Thus, excessive CXCL1
      expression in gp130-deficient endothelial cells augments neutrophil adhesion but
      hinders migration, most likely by disrupting chemotactic gradients. Our data
      define a role for endothelial cell gp130 in regulating integrin-dependent
      adhesion and de-adhesion of neutrophils during inflammation. 

PMID- 24081663
TI  - Unilateral retinopathy secondary to occult primary intraocular lymphoma.
AB  - PURPOSE: The purpose of the study is to report the clinical case of a 53-year-old
      woman whose presenting manifestation of primary intraocular lymphoma (PIOL) was
      unilateral retinal degeneration. METHOD: A case report was created with review of
      clinical, imaging, electrophysiologic, and pathological investigations. RESULTS:
      A 53-year-old woman with a distant history of ocular herpes simplex developed
      progressive central visual loss and intermittent photopsia over 4 years in her
      right eye. Ophthalmic examination revealed reduced visual acuity OD, central
      scotoma, and minimal ocular findings. Autofluorescence and infrared imaging
      revealed mild reflectance changes in the temporal macula, and spectral-domain
      optical coherence tomography identified mild disruptions of inner segment/outer
      segment junctions in the subfoveal region of the right eye. A mild window defect
      was seen on fluorescein angiography. Electrophysiology with multifocal
      electroretinogram (ERG) revealed evidence of unilateral macular dysfunction. Full
      field ERGs revealed progressive global retinal dysfunction over 6 months, with
      unilateral decreases in amplitude and implicit time shifts, as seen in cases of
      autoimmune retinopathies. The eye eventually exhibited mild vitreous cellular
      infiltration on ophthalmoscopic examination, and vitrectomy diagnosed B cell non
      Hodgkin's lymphoma. Further evaluation revealed no evidence of central nervous
      system or systemic disease, consistent with occult PIOL. CONCLUSIONS: This case
      illustrates an atypical presentation of PIOL characterized by unilateral retinal
      disease presenting with symptoms and signs of macular dysfunction. Clinical and
      ERG features evolved into an acute zonal occult outer retinopathy (AZOOR)-like
      phenotype. PIOL should be considered in atypical cases of AZOOR with vitreal
      reactions, and some cases of AZOOR may be related to B cell lymphocyte disorders.

PMID- 24081664
TI  - Giants in orthopaedic surgery: Sterling Bunnell MD.

PMID- 24081665
TI  - Can regional anesthesia and analgesia prolong cancer survival after orthopaedic
      oncologic surgery?
AB  - BACKGROUND: The perioperative period of major oncologic surgery is characterized
      by immunosuppression, angiogenesis, and an increased load of circulating
      malignant cells. It is a window period in which cancer cells may seed, invade,
      and proliferate. Thus, it has been hypothesized that the use of regional
      anesthesia with the goal of reducing surgical stress and opioid and volatile
      anesthetic consumption would avoid perioperative immune suppression and
      angiogenesis and ultimately cancer recurrence. QUESTIONS/PURPOSES: We performed a
      systematic review of the literature on the use of regional anesthesia and
      postoperative analgesia to improve cancer-related survival after oncologic
      surgery. Our primary topic of interest is survival after orthopaedic oncologic
      surgery, but because that literature is limited, we also have systematically
      reviewed the question of survival after breast, gastrointestinal, and
      genitourologic cancers. METHODS: We searched the PubMed and Embase databases with
      the search terms: "anesthesia and analgesia", "local neoplasm recurrence",
      "cancer recurrence", "loco-regional neoplasm recurrence", "disease-free
      survival", and "cumulative survival rates". Our initial search of the two
      databases provided 836 studies of which 693 were rejected. Of the remaining 143
      studies, only 13 articles qualified for inclusion in this systematic review,
      based on defined inclusion criteria. All these studies had retrospective design.
      Due to the high heterogeneity among the identified studies and the complete
      absence of randomized controlled trials from the literature on this topic, the
      results of a meta-analysis would be heavily confounded; hence, we instead
      performed a systematic review of the literature. RESULTS: No eligible studies
      addressed the question of whether regional anesthesia and analgesia have an
      impact on survival after musculoskeletal cancer surgery. Only one relevant
      clinical study was identified on regional breast cancer survival; it suggested a
      benefit. The literature on gastrointestinal and genitourinary surgery was larger
      but mixed, although some preliminary studies do suggest a benefit of regional
      anesthesia on survival after oncologic surgery in those patient populations.
      CONCLUSIONS: Although basic science studies suggest a potential benefit of
      regional anesthesia and stress response reduction in cancer formation, we found
      little clinical evidence to support the theory that regional anesthesia and
      analgesia improve overall patient survival after oncologic surgery.

PMID- 24081666
TI  - High metal ion levels after use of the ASRTM device correlate with development of
      pseudotumors and T cell activation.
AB  - BACKGROUND: Pseudotumors and immunologic alterations are reported in patients
      with elevated metal ion levels after resurfacing arthroplasty of the hip. A
      direct association of increased cobalt and chromium concentrations with the
      development of pseudotumors has not been established. QUESTIONS/PURPOSES: We
      hypothesized that (1) patients with higher blood cobalt and chromium
      concentrations are more likely to have pseudotumors develop, (2) elevated cobalt
      and chromium concentrations correlate with increased activation of defined T cell
      populations, and (3) elevated metal ion levels, small implant size, cup
      inclination angle, and patient age are risk factors for the development of
      pseudotumors. METHODS: A single-surgeon cohort of 78 patients with 84 Articular
      Surface Replacement((r)) implants was retrospectively investigated. Between 2006
      and 2010, we performed 84 THAs using the Articular Surface Replacement((r))
      implant; this represented 2% (84/4950) of all primary hip replacements performed
      during that period. Of the procedures performed using this implant, we screened
      77 patients (99%) at a mean of 43 months after surgery (range, 24-60 months).
      Seventy-one patients were investigated using ultrasound scanning, and cobalt and
      chromium concentrations in whole blood were determined by high-resolution
      inductively coupled plasma mass spectrometry. Differential analysis of lymphocyte
      subsets was performed by flow cytometry in 53 patients. Results of immunologic
      analyses were investigated separately for patients with and without pseudotumors.
      Pseudotumors were found in 25 hips (35%) and were more common in women than in
      men (p = 0.02). Multivariable regression analysis was performed to identify risk
      factors for the development of pseudotumors. RESULTS: Cobalt and chromium
      concentrations were greater in patients with pseudotumors than in those without
      (cobalt, median 8.3 versus median 1.0 MUg/L, p < 0.001; chromium, median 5.9
      versus median 1.3 MUg/L, p < 0.001). The percentage of HLA-DR(+)CD4(+) T cells
      was greater in patients with pseudotumors than in those without (p = 0.03), and
      the proportion of this lymphocyte subtype was positively correlated with cobalt
      concentrations (r = 0.3, p = 0.02). Multivariable regression analysis indicated
      that increasing cobalt levels were associated with the development of
      pseudotumors (p < 0.001), and that patients with larger implants were less likely
      to have them develop (p = 0.04); age and cup inclination were not risk factors.
      CONCLUSIONS: We found a distinct association of elevated metal ion concentrations
      with the presence of pseudotumors and a correlation of increased cobalt
      concentrations with the proportion of activated T helper/regulator cells. Thus,
      the development of soft tissue masses after metal-on-metal arthroplasty could be
      accompanied by activation of T cells, indicating that this complication may be
      partly immunologically mediated. Further investigations of immunologic parameters
      in larger cohorts of patients with metal-on-metal arthroplasties are warranted.
      LEVEL OF EVIDENCE: Level III, therapeutic study. See the Instructions for Authors
      for a complete description of levels of evidence.

PMID- 24081667
TI  - Cemented versus uncemented hemiarthroplasty for displaced femoral neck fractures:
      5-year followup of a randomized trial.
AB  - BACKGROUND: Displaced femoral neck fractures usually are treated with
      hemiarthroplasty. However, the degree to which the design of the implant used
      (cemented or uncemented) affects the outcome is not known and may be
      therapeutically important. QUESTIONS/PURPOSES: In this randomized controlled
      trial, we sought to compare cemented with cementless fixation in bipolar
      hemiarthroplasties at 5 years in terms of (1) Harris hip scores; (2) femoral
      fractures; (3) overall health outcomes using the Barthel Index and EQ-5D scores;
      and (4) complications, reoperations, and mortality since our earlier report on
      this cohort at 1-year followup. METHODS: We present followup at a median of 5
      years after surgery (range, 56-65 months) from a randomized trial comparing a
      cemented hemiarthroplasty (112 hips) with an uncemented, hydroxyapatite-coated
      hemiarthroplasty (108 hips), both with a bipolar head. Results were previously
      reported at 1-year followup. Harris hip scores, Barthel Index, and EQ-5D scores
      were assessed by one research nurse and one orthopaedic surgeon. Complications
      and reoperations were determined by chart review and radiographs examined by
      three orthopaedic surgeons. Sixty patients (56%) had died in the cemented group
      and 63 (60%) in the uncemented group. Respectively, three and two patients (2.7%
      and 1.9%) were completely lost to followup. RESULTS: Harris hip scores at 5 years
      were higher in the uncemented group than in the cemented group (86.2 versus 76.3;
      mean difference 9.9; 95% confidence interval [CI], 1.9-17.9). The prevalence of
      postoperative periprosthetic femoral fractures was 7.4% in the uncemented group
      and 0.9% in the cemented group (hazard ratio [HR], 9.3; 95% CI, 1.16-74.5).
      Barthel Index and EQ-5D scores were not different between the groups. Between 1
      and 5 years, we found no additional infections or dislocations. The mortality
      rate was not different between the groups (HR, 1.2; 95% CI, 0.82-1.7).
      CONCLUSIONS: Both arthroplasties may be used with good medium-term results after
      displaced femoral neck fractures. The uncemented hemiarthroplasty may result in
      higher hip scores but appears to carry an unacceptably high risk of later femoral
      fractures. LEVEL OF EVIDENCE: Level I, therapeutic study. See the Guidelines for
      Authors for a complete description of levels of evidence.

PMID- 24081668
TI  - Symposium: 2012 International Hip Society Proceedings.

PMID- 24081669
TI  - What are the levels of evidence on which we base decisions for surgical
      management of lower extremity bone tumors?
AB  - BACKGROUND: Benign and malignant lower extremity primary bone tumors are among
      the least common conditions treated by orthopaedic surgeons. The literature
      supporting their surgical management has historically been in the form of
      observational studies rather than prospective controlled studies. Observational
      studies are prone to confounding bias, sampling bias, and recall bias.
      QUESTIONS/PURPOSES: (1) What are the overall levels of evidence of articles
      published on the surgical management of lower extremity bone tumors? (2) What is
      the overall quality of reporting of studies in this field based on the
      Strengthening the Reporting of Observational Studies in Epidemiology (STROBE)
      checklist? (3) What are the most common pitfalls in reporting that authors might
      improve on? METHODS: All studies describing the surgical management of lower
      extremity primary bone tumors from 2002 to 2012 were systematically reviewed. Two
      authors independently appraised levels of evidence. Quality of reporting was
      assessed with the STROBE checklist. Pitfalls in reporting were quantified by
      determining the 10 most underreported elements of research study design in the
      group of studies analyzed, again using the STROBE checklist as the reference
      standard. Of 1387 studies identified, 607 met eligibility criteria. RESULTS:
      There were no Level I studies, two Level II studies, 47 Level III studies, 308
      Level IV studies, and 250 Level V studies. The mean percentage of STROBE points
      reported satisfactorily in each article as graded by the two reviewers was 53%
      (95% confidence interval, 42%-63%). The most common pitfalls in reporting were
      failures to justify sample size (2.2% reported), examine sensitivity (2.2%),
      account for missing data (9.8%), and discuss sources of bias (14%). Followup
      (66%), precision of outcomes (64%), eligibility criteria (55%), and
      methodological limitations (53%) were variably reported. CONCLUSIONS:
      Observational studies are the dominant evidence for the surgical management of
      primary lower extremity bone tumors. Numerous deficiencies in reporting limit
      their clinical use. Authors may use these results to inform future work and
      improve reporting in observational studies, and treating surgeons should be aware
      of these limitations when choosing among the various options with their patients.

PMID- 24081671
TI  - Retinal vessel detection and measurement for computer-aided medical diagnosis.
AB  - Since blood vessel detection and characteristic measurement for ocular retinal
      images is a fundamental problem in computer-aided medical diagnosis, automated
      algorithms/systems for vessel detection and measurement are always demanded. To
      support computer-aided diagnosis, an integrated approach/solution for vessel
      detection and diameter measurement is presented and validated. In the proposed
      approach, a Dempster-Shafer (D-S)-based edge detector is developed to obtain
      initial vessel edge information and an accurate vascular map for a retinal image.
      Then, the appropriate path and the centerline of a vessel of interest are
      identified automatically through graph search. Once the vessel path has been
      identified, the diameter of the vessel will be measured accordingly by the
      algorithm in real time. To achieve more accurate edge detection and diameter
      measurement, mixed Gaussian-matched filters are designed to refine the initial
      detection and measures. Other important medical indices of retinal vessels can
      also be calculated accordingly based on detection and measurement results. The
      efficiency of the proposed algorithm was validated by the retinal images obtained
      from different public databases. Experimental results show that the vessel
      detection rate of the algorithm is 100 % for large vessels and 89.9 % for small
      vessels, and the error rate on vessel diameter measurement is less than 5 %,
      which are all well within the acceptable range of deviation among the human
      graders. 

PMID- 24081672
TI  - Significance and prognostic value of Gli-1 and Snail/E-cadherin expression in
      progressive gastric cancer.
AB  - Abnormal activation of the hedgehog (Hh) signaling pathway has been found to be
      involved in the occurrence, invasion, and metastasis of cancers. Epithelial
      mesenchymal transition (EMT) also plays an important role in the invasion and
      metastasis of cancers. However, the significance of the Hh signaling pathway and
      EMT in the invasion and metastasis of gastric cancer is still unclear. This study
      aimed to investigate the significance and prognostic value of the Hh signaling
      pathway and EMT in progressive gastric cancer. Immunohistochemistry was performed
      to detect the expression of the Hh-induced transcriptional factor Gli-1 and the
      EMT-related molecules Snail and E-cadherin in 121 patients with progressive
      gastric cancer. Histological type, depth of invasion, lymph node metastasis, and
      pTNM stage were also recorded. In progressive gastric cancer, Gli-1 expression
      increased markedly, and was closely associated with increased Snail expression
      and decreased E-cadherin expression. Diffuse type cancer, lymph node metastasis,
      and abnormal expression of E-cadherin were independent factors influencing the
      prognosis of patients with progressive gastric cancer. These findings suggest
      that abnormal activation of the Hh signaling pathway is closely related to the
      presence of EMT and is an important factor influencing the prognosis of patients
      with diffuse progressive gastric cancer.

PMID- 24081674
TI  - Antitumor effect of fructose 1,6-bisphosphate and its mechanism in hepatocellular
      carcinoma cells.
AB  - We aimed to investigate the antitumor effect and mechanism of fructose 1,6
      bisphosphate (F1,6BP) in a hepatocellular carcinoma cell line. HepG2 cells were
      treated with different concentrations of F1,6BP alone or in combination with
      antioxidant N-acetyl-L-cysteine (NAC) or catalase (CAT), and cell proliferation
      assays were performed. Nuclear morphology was observed by fluorescence microscopy
      after Hoechst staining, and apoptosis was measured with flow cytometry. Changes
      in reactive oxygen species (ROS) levels in HepG2 cells were detected by 2',7'
      dichlorodihydrofluorescein diacetate (DCFH-DA) staining. A colorimetric assay was
      adopted to determine the percentage of oxidized glutathione in these cells. CAT
      and glutathione peroxidase (GSH-Px) mRNA expression levels in HepG2 cells were
      measured by real-time fluorescence quantitative PCR. HepG2 cell proliferation was
      significantly inhibited by F1,6BP, accompanied by an increase in intracellular
      ROS levels and oxidized glutathione. Upregulated apoptosis and characteristic
      nuclear morphological changes were observed, and the expression of CAT and GSH-Px
      mRNA was increased after F1,6BP treatment. The antitumor effect of F1,6BP was
      significantly decreased after pretreatment with NAC and CAT in HepG2 cells. In
      conclusion, F1,6BP can induce the apoptosis of HepG2 cells. The mechanism
      involved may be associated with the generation of ROS, especially the production
      of H2O2. 

PMID- 24081673
TI  - The function, mechanisms, and role of the genes PTEN and TP53 and the effects of
      asbestos in the development of malignant mesothelioma: a review focused on the
      genes' molecular mechanisms.
AB  - The malignant mesothelioma is an aggressive form of cancer with a mean survival
      rate of less than a year. Moreover, environmental exposure to minerals is an
      important factor in the development of malignant mesothelioma (MM), especially
      the mineral asbestos, which has a well-documented role in MM, and more recently,
      the mineral erionite has been proven to be a strong carcinogenic inducer of MM.
      In addition, the virus simian virus 40 has been implicated as a co-carcinogenic
      player in MM. However, the molecular mechanisms involved in the pathogenesis of
      this cancer are still not fully understood. Indeed, it is known that several
      genes are altered or mutated in MM, among those are p16(INK4A), p14(ARF), and
      neurofibromatosis type II. Furthermore, TP53 has been reported to be mutated in
      the majority of the cancers; however, in MM, it is very uncommon mutations in
      this gene. Also, the PTEN gene has been shown to play an important role in
      endometrial cancer and glioblastoma, although the role of PTEN in MM has yet to
      be established. Taken altogether, this review focuses on the historical aspects,
      molecular mechanisms, interaction with other genes and proteins, and the role of
      these genes in MM. Lastly, this review questions the cancer theory of the two
      hits because the functions of both PTEN and TP53 are not fully explained by this
      theory. 

PMID- 24081675
TI  - Fibronectin overexpression is associated with latent membrane protein 1
      expression and has independent prognostic value for nasopharyngeal carcinoma.
AB  - Despite recent improvements in the diagnosis and treatment, the final outcomes in
      patients with nasopharyngeal carcinomas (NPC) still remain suboptimal. Through
      data mining from published transcriptomic database with further bioinformatic
      validation, fibronectin (FN1) was identified as a differentially upregulated gene
      in NPC tissues, which implicates the transition from epithelial to mesenchymal
      phenotype (EMT) and promotes metastasis. Given the roles of fibronectin in risk
      stratification and in the frontline therapeutics of common carcinomas, such as
      renal cell cancer, we explored fibronectin immunoexpression status and its
      associations with clinicopathological variables and survival in a well-defined
      cohort of NPC patients. Fibronectin immunohistochemistry was retrospectively
      performed and analyzed using H-score for 124 biopsy specimens from NPC patients
      who received standard treatment without distant metastasis at initial diagnosis.
      Those cases with H-score higher than the median value were regarded as
      fibronectin overexpression. The findings were correlated with clinicopathological
      variables, EBV latent membrane protein 1 (LMP1) expression, disease-specific
      survival (DSS), distant metastasis-free survival (DMFS), and local recurrence
      free survival (LRFS). Fibronectin overexpression was significantly associated
      with American Joint Committee on Cancer (AJCC) stages III-IV (p = 0.019) and LMP1
      expression (p = 0.004), and univariately predictive of adverse outcomes for DSS,
      DMFS, and LRFS (all p < 0.0001). In the multivariate comparison, fibronectin
      overexpression still remained prognostically independent to portend worse DSS (p
      < 0.01, hazard ratio = 5.958), DMFS (p < 0.01, hazard ratio = 5.728), and LRFS (p
      < 0.01, hazard ratio = 5.411) together with a vanced AJCC stages III-IV.
      Fibronectin is upregulated in a subset of NPCs, and its increased
      immunoexpression significantly correlated with advanced features, justifying the
      potentiality of fibronectin as a theragnostic biomaker of NPC.

PMID- 24081676
TI  - The apoptotic effect of shikonin on human papillary thyroid carcinoma cells
      through mitochondrial pathway.
AB  - This study aims to explore the apoptotic function of shikonin on the papillary
      thyroid cancer cells and the related mechanism. The papillary thyroid cancer cell
      lines K1 and W3 and thyroid follicular epithelial cells NTHY-ORI 3-1 were treated
      with different concentrations of shikonin. Cell proliferation was tested.
      Morphological changes of the apoptotic cells were observed by Hoechst 33342
      staining. The apoptosis rate of the papillary thyroid cancer cells was measured
      with flow cytometry. Changes of the cell cycle were explored. The mitochondrial
      membrane potential changes were analyzed after JC-1 staining. Bcl-2 family
      proteins and caspase-3 expression with shikonin treatment was analyzed by real
      time fluorescence polymerase chain reaction (PCR). Cell proliferation of K1 and
      W3 was inhibited by shikonin, and the inhibition was dose-time dependent.
      Papillary thyroid carcinoma cells treated by shikonin had no obvious cell cycle
      arrest but were observed with the higher apoptosis rate and the typical apoptotic
      morphological changes of the cell nucleus. JC-1 staining showed that shikonin
      reduced the mitochondrial membrane potential of papillary thyroid carcinoma
      cells. Real-time PCR results showed that shikonin significantly increased Bax and
      caspase-3 expression and upregulated Bcl-2 expression in a dose-dependent manner
      in papillary thyroid carcinoma cells. However, the NTHY-ORI 3-1 was almost not
      affected by shikonin treatment. Shikonin can inhibit K1 and W3 cell proliferation
      in a dose- and time-dependent manner, enhance Bax levels, reduce anti-apoptotic
      protein Bcl-2 levels, result in decreasing mitochondrial membrane potential and
      activating caspase-3 enzyme, and finally lead to apoptosis. 

PMID- 24081677
TI  - Delayed growth of glioma by a polysaccharide from Aster tataricus involve
      upregulation of Bax/Bcl-2 ratio, activation of caspase-3/8/9, and downregulation
      of the Akt.
AB  - In this study, a homogeneous polysaccharide (ATP-II), with a molecular weight of
      3.4 * 10(4) Da, was successfully purified from Aster tataricus by DEAE-Sepharose
      CL-6B ion exchange and Sepharose CL-6B gel filtration chromatography.
      Monosaccharide component analysis indicated that ATP-II was composed of glucose,
      galactose, mannose, rhamnose, and arabinose in molar ratios of
      2.1:5.2:2.1:1.0:1.2. We evaluated the anticancer efficacy and associated
      mechanisms of ATP-II on glioma C6 cells in vitro and in vivo. The results showed
      that treatment of C6 cells with ATP-II inhibited cell proliferation and this
      biological response came from induction of DAN damage and consequent inducing
      apoptosis. Likewise, oral ATP-II administration resulted in consistent regression
      of glioma tumors and induced apoptosis of transplanted tumor tissues by
      increasing the ratio of Bax/Bcl-2 and activation of caspase-3, caspase-8, and
      caspase-9 cascade. Importantly, the efficient downregulation of Akt, which is
      successfully detected in tumor tissues, is a unique contribution to retard the
      tumor growth by ATP-II. These data suggest that ATP-II may be a potential
      candidate for glioma treatment. 

PMID- 24081678
TI  - Odor tracking flight of male Manduca sexta moths along plumes of different cross
      sectional area.
AB  - Males of the hawkmoth, Manduca sexta, track wind-borne plumes of female sex
      pheromone by flying upwind, while continuously turning from side-to-side and
      changing altitude. Their characteristic "zigzagging" trajectory has long been
      thought to result from the interaction of two mechanisms, an odor-modulated
      orientation to wind and a built-in central nervous system turning program. An
      interesting and as of yet unanswered question about this tracking behavior is how
      the cross-section of an odor plume or its clean-air "edges" affects moths' odor
      tracking behavior. This study attempts to address this question by video
      recording and analyzing the behavior of freely flying M. sexta males tracking
      plumes from pheromone sources of different lengths and orientations with equal
      odor concentration per unit area. Our results showed that moths generated
      significantly wider tracks in wide plumes from the longest horizontally-oriented
      sources as compared to narrower point-source plumes, but had relatively unaltered
      tracks when orienting to plumes from the same length sources oriented vertically.
      This suggests that in addition to wind and the presence of pheromones, the area
      of the plume's cross section or its edges may also play an important role in the
      plume tracking mechanisms of M. sexta. 

PMID- 24081679
TI  - A model for combined targeting and tracking tasks in computer applications.
AB  - Current models for targeted-tracking are discussed and shown to be inadequate as
      a means of understanding the combined task of tracking, as in the Drury's
      paradigm, and having a final target to be aimed at, as in the Fitts' paradigm. It
      is shown that the task has to be split into components that are, in general,
      performed sequentially and have a movement time component dependent on the
      difficulty of the individual component of the task. In some cases, the task time
      may be controlled by the Fitts' task difficulty, and in others, it may be
      dominated by the Drury's task difficulty. Based on an experiment carried out that
      captured movement time in combinations of visually controlled and ballistic
      movements, a model for movement time in targeted-tracking was developed. 

PMID- 24081680
TI  - Humans robustly adhere to dynamic walking principles by harnessing motor
      abundance to control forces.
AB  - Human walking dynamics are typically framed in the context of mechanics and
      energetics rather than in the context of neuromuscular control. Dynamic walking
      principles describe one helpful theoretical approach to characterize efficient
      human walking mechanics over many steps. These principles do not, however,
      address how such walking is controlled step-by-step despite small perturbations
      from natural variability. Our purpose was to identify neuromechanical control
      strategies used to achieve consistent and robust locomotion despite natural step
      to-step force variability. We used the uncontrolled manifold concept to test
      whether human walkers select combinations of leading and trailing leg-forces that
      generate equivalent net-force trajectories during step-to-step transitions.
      Subjects selected leading and trailing leg-force combinations that generated
      consistent vertical net-force during step-to-step transitions. We conclude that
      vertical net-force is an implicit neuromechanical goal of human walking whose
      trajectory is stabilized for consistent step-to-step transitions, which agrees
      with the principles of dynamic walking. In contrast, inter-leg-force combinations
      modulated anterior-posterior net-force trajectories with each step to maintain
      constant walking speed, indicating that a consistent anterior-posterior net-force
      trajectory is not an implicit goal of walking. For a more complete picture of
      hierarchical locomotor control, we also tested whether each individual leg-force
      trajectory was stabilized through the selection of leg-force equivalent joint
      torque combinations. The observed consistent vertical net-force trajectory was
      achieved primarily through the selection of joint-torque combinations that
      modulated trailing leg-force during step-to-step transitions. We conclude that
      humans achieve robust walking by harnessing inherent motor abundance of the
      joints and legs to maintain consistent step-by-step walking performance. 

PMID- 24081681
TI  - Motor unit properties from three synergistic muscles during ramp isometric elbow
      extensions.
AB  - Many tasks require synergistic activation of muscles that possess different
      architectural, mechanical, and neural control properties. However, investigations
      of the motor unit (MU) mechanisms which modulate force are mostly restricted to
      individual muscles and low forces. To explore the pattern of MU recruitment and
      discharge behavior among three elbow extensors (lateral and long heads of the
      triceps brachii, and anconeus) during ramp isometric contractions, recruitment
      thresholds of 77 MUs in five young men were determined and corresponding MU
      discharge rates were tracked in 1-s epochs over forces ranging from 0 to 75 % of
      maximal voluntary isometric force (MVC). Across all forces, MUs in the lateral
      head discharged at higher rates than those in the anconeus (p < 0.001, Delta =
      0.23). When all MUs were considered, recruitment thresholds in the long head of
      the triceps brachii were higher than the lateral head (p < 0.05, Delta = 0.70)
      with a trend (p = 0.08, Delta = 0.48) for higher recruitment thresholds in the
      long head compared with the anconeus. Together, these data indicate a potential
      mechanical disadvantage of the long head of the triceps brachii at 0 degrees 
      shoulder flexion. However, among low-threshold MUs (<10 % MVC), recruitment
      thresholds were lower in the anconeus than in both heads of the triceps brachii
      consistent with the expected twitch contractile and fiber type differences among
      these muscles. These findings illustrate the importance of considering
      synergistic relations among muscles used for a coordinated task, and the
      sensitivity of synergies to muscle architectural, mechanical, and possibly
      specific synaptic input factors. 

PMID- 24081682
TI  - Challenges to conducting a clinical trial of combination therapy of colistin and
      rifampicin for extensively drug-resistant Acinetobacter baumannii.

PMID- 24081684
TI  - Reply to Huang et al.

PMID- 24081683
TI  - Evaluation of hepatitis C virus as a risk factor for HIV-associated neuroretinal
      disorder.
AB  - BACKGROUND: Both hepatitis C virus (HCV) and human immunodeficiency virus (HIV)
      penetrate the central nervous system. HIV-associated neuroretinal disorder (HIV
      NRD), a visual impairment of reduced contrast sensitivity and reading ability, is
      associated with cytokine dysregulation and genetic polymorphisms in the anti
      inflammatory interleukin 10 (IL-10) signaling pathway. We investigated
      associations between HCV and HIV-NRD and between HCV and single-nucleotide
      polymorphisms (SNPs) in the IL-10 receptor 1 (IL10R1) gene. METHODS: Logistic and
      Cox regression analysis were used to analyze risk factors for HIV-NRD in 1576 HIV
      positive patients who did not have an ocular opportunistic infection at
      enrollment. Median follow-up was 4.9 years (interquartile range, 2.4-8.8 years).
      Four IL10R1 SNPs were examined in a subset of 902 patients. RESULTS: The group
      included 290 patients with chronic HCV infection, 74 with prior infection, and
      1212 with no HCV markers. There were 244 prevalent cases of HIV-NRD and 263
      incident cases (rate = 3.9/100 person-years). In models adjusted for
      demographics, HIV treatment and status, liver function, and immune status, both
      the prevalence and incidence of HIV-NRD were significantly higher in patients
      with chronic HCV infection (odds ratio = 1.54; 95% confidence interval [CI], 1.03
      2.31 and hazard ratio = 1.62; 95% CI, 1.13-2.34, respectively), compared to
      patients with no HCV markers. Chronic HCV was associated with rs2228055 and 2
      additional IL-10R1 SNPs expected to reduce IL-10 signaling. HIV-NRD was not
      significantly associated with these SNPs. CONCLUSIONS: HCV is a possible risk
      factor for HIV-NRD. Genetic analysis suggests that alterations in the IL-10
      signaling pathway may increase susceptibility to HIV-NRD and HCV infection.
      Inflammation may link HCV and HIV-NRD.

PMID- 24081685
TI  - A new anti-acetylcholinesterase alpha-pyrone meroterpene, arigsugacin I, from
      mangrove endophytic fungus Penicillium sp. sk5GW1L of Kandelia candel.
AB  - Arigsugacin I (1), a new alpha-pyrone meroterpene, along with two known
      compounds, arigsugacins F (2) and territrem B (3), were isolated from the
      mangrove endophytic fungus Penicillium sp. sk5GW1L from Kandelia candel. Their
      structures were identified through mass spectrometry and NMR experiments, and the
      absolute configuration of compound 1 was further confirmed by low-temperature
      (100 K) single crystal X-ray diffraction with Cu Kalpha radiation. The absolute
      configuration of compound 2 was first reported by using X-ray copper radiation.
      Compounds 1-3 showed inhibitory activities against acetylcholinesterase with IC50
      values of 0.64 +/- 0.08 uM, 0.37 +/- 0.11 uM, and 7.03 +/- 0.20 nM, respectively.

PMID- 24081686
TI  - Chemical constituents from the roots and stems of Erycibe obtusifolia and their
      in vitro antiviral activity.
AB  - Three new quinic acid derivatives, 4-O-caffeoyl-3-O-sinapoylquinic acid methyl
      ester (1), 5-O-caffeoyl-4-O-syringoylquinic acid methyl ester (2), and 4-O
      caffeoyl-3-O-syringoylquinic acid methyl ester (3), as well as four new coumarin
      glycosides, 7-O-(3-O-sinapoyl-beta-D-glucopyranosyl)-6-methoxycoumarin (12), 7-O
      (6-O-sinapoyl-beta-D-glucopyranosyl)-6-methoxycoumarin (13), 7-O-(2-O-sinapoyl
      beta-D-glucopyranosyl)-6-methoxycoumarin (14), and 7-O-(6-O-syringoyl-beta-D
      glucopyranosyl)-6-methoxycoumarin (15), together with eight known compounds (4
      11) were isolated from the roots and stems of Erycibe obtusifolia. Their
      structures were elucidated on the basis of spectroscopic analysis and chemical
      evidence. All the compounds were screened for their in vitro antiviral activity
      against respiratory syncytial virus with a cytopathic effect reduction assay.
      Among them, the di-O-caffeoyl quinates 8-11 displayed a potent in vitro anti
      respiratory syncytial virus effect. 

PMID- 24081687
TI  - Herbacetin, a constituent of ephedrae herba, suppresses the HGF-induced motility
      of human breast cancer MDA-MB-231 cells by inhibiting c-Met and Akt
      phosphorylation.
AB  - Ephedrae herba suppresses hepatocyte growth factor-induced cancer cell motility
      by inhibiting tyrosine phosphorylation of the hepatocyte growth factor receptor,
      c-Met, and the PI3K/Akt pathway. Moreover, Ephedrae herba directly inhibits the
      tyrosine-kinase activity of c-Met. Ephedrine-type alkaloids, which are the active
      component of Ephedrae herba, do not affect hepatocyte growth factor-c-Met-Akt
      signalling, prompting us to study other active molecules in the herb. We recently
      discovered herbacetin glycosides and found that their aglycon, herbacetin,
      inhibits hepatocyte growth factor-c-Met-Akt signalling. This study revealed a
      novel biological activity of herbacetin. Herbacetin suppressed hepatocyte growth
      factor-induced motility in human breast cancer MDA-MB-231 cells by inhibiting c
      Met and Akt phosphorylation and directly inhibiting c-Met tyrosine kinase
      activity. The effects of herbacetin were compared to those of kaempferol,
      apigenin, and isoscutellarein, all of which have similar structures. Herbacetin
      inhibition of hepatocyte growth factor-induced motility was the strongest of
      those for the tested flavonols, and only herbacetin inhibited the hepatocyte
      growth factor-induced phosphorylation of c-Met. These data suggest that
      herbacetin is a novel Met inhibitor with a potential utility in cancer
      therapeutics. 

PMID- 24081688
TI  - Clinical characteristics and treatment options for two types of osteoblastoma in
      the mobile spine: a retrospective study of 32 cases and outcomes.
AB  - PURPOSE: A retrospective study of 32 patients with osteoblastoma (OBL) in the
      mobile spine was performed to analyze the clinical characteristics of two types
      of spinal OBL. We also aimed to find influential factors for OBL in the mobile
      spine. METHODS: Between 2002 and 2011, 32 patients with either conventional
      osteoblastoma (CO) or aggressive osteoblastoma (AO) in the mobile spine were
      treated in our center. All patients were treated with either total excision or
      subtotal excision + postoperative radiotherapy. The mean follow-up was 45.8 (18
      128) months. Clinical data and surgery efficacy were analyzed to search for
      clinical characteristics of two subtypes of spinal OBL and discuss the possible
      factors influencing relapse. RESULTS: There is significant difference between CO
      and AO in tumor size (p < 0.0005), preoperative alkaline phosphatase (ALP, p <
      0.0005) and intraoperative blood loss (p = 0.013). Multivariate logistic
      regression was used to find the influential factors for relapse and the results
      were: preoperative ALP, b = 0.023, p = 0.029; surgery protocol, b = -7.597, p =
      0.007; tumor size, >=3/<3, b = 24.805, p < 0.0005; age, b = 0.054, p = 0.632; and
      pathology type, b = 1.998, p = 0.34. CONCLUSIONS: Tumor size, preoperative ALP
      and CT images were helpful for distinguishing AO from CO. The difference in
      intraoperative blood loss between CO and AO is mainly attributed to the size of
      the lesion. Preoperative ALP, surgery protocol and tumor size (>=3/<3) were
      considered to significantly influence relapse of spinal OBL.

PMID- 24081689
TI  - One-stage anterior debridement, bone grafting and posterior instrumentation vs.
      single posterior debridement, bone grafting, and instrumentation for the
      treatment of thoracic and lumbar spinal tuberculosis.
AB  - PURPOSE: The aim of this study was to compare single posterior debridement,
      interbody fusion and instrumentation with one-stage anterior debridement,
      interbody fusion and posterior instrumentation for treating thoracic and lumbar
      spinal tuberculosis. METHOD: From January 2006 to January 2010, we enrolled 115
      spinal tuberculosis patients with obvious surgical indications. Overall, 55
      patients had vertebral body destruction, accompanied by a flow injection abscess
      or a unilateral abscess volume greater than 500 ml. The patients underwent one
      staged anterior debridement, bone grafting and posterior instrumentation (group
      A) or single posterior debridement, bone grafting and instrumentation (group B).
      Clinical and radiographic results for the two groups were analyzed and compared.
      RESULTS: Patients were followed 12-36 months (mean 21.3 months), Fusion occurred
      at 4-12 months (mean 7.8 months). There were significant differences between
      groups regarding the post-operative kyphosis angle, angle correction and angle
      correction rate, especially if pathology is present in thoracolumbar and lumbar
      regions. Operative complications affected five patients in group A, and one
      patient in group B. A unilateral psoas abscess was observed in three patients 12
      months postoperatively. In one of them, interbody fusion did not occur, and there
      was fixation loosening and interbody absorption. All of them were cured by an
      anterior operation. CONCLUSION: Anterior debridement and bone grafting with
      posterior instrumentation may not be the best choice for treating patients with
      spinal tuberculosis. Single posterior debridement/bone grafting/instrumentation
      for single-segment of thoracic or lumbar spine tuberculosis produced good
      clinical results, except in patients who had a psoas abscess.

PMID- 24081690
TI  - Lumbar foraminal stenosis causes leg pain at rest.
AB  - PURPOSE: Lumbar intra-spinal canal stenosis is characterized by leg pain that
      intensifies during walking and intermittent claudication, while leg pain at rest
      is a characteristic neurological symptom of lumbar disc herniation. Until now, a
      correlation between leg pain at rest and symptomatic foraminal stenosis has not
      been reported. This is a prospective and comparative study of unilateral leg pain
      from L5 nerve root compression due to spinal canal stenosis to determine clinical
      characteristics of lumbar foraminal stenosis. METHODS: Clinical and neurological
      findings were compared among 38 patients receiving L5-S1 transforaminal lumbar
      interbody fusion for L5-S1 foraminal stenosis (FS group) and 60 patients
      receiving L4-5 decompression or/and fusion for L4-5 intra-spinal canal stenosis
      (CS group). RESULTS: The only significant difference between the FS and CS groups
      in demographic clinical data was leg pain at rest. The prevalence of leg pain was
      significantly higher in the FS group compared to the CS group (76 vs. 35%). The
      visual analogue scale for leg pain at rest was also significantly higher in the
      FS group than in the CS group (6.6 +/- 3.1 vs. 1.3 +/- 1.9). CONCLUSIONS: Leg
      pain at rest is characteristic of L5-S1 foraminal stenosis.

PMID- 24081691
TI  - Novel antifungal alpha-hairpinin peptide from Stellaria media seeds: structure,
      biosynthesis, gene structure and evolution.
AB  - Plant defense against disease is a complex multistage system involving initial
      recognition of the invading pathogen, signal transduction and activation of
      specialized genes. An important role in pathogen deterrence belongs to so-called
      plant defense peptides, small polypeptide molecules that present antimicrobial
      properties. Using multidimensional liquid chromatography, we isolated a novel
      antifungal peptide named Sm-AMP-X (33 residues) from the common chickweed
      (Stellaria media) seeds. The peptide sequence shows no homology to any previously
      described proteins. The peculiar cysteine arrangement (C(1)X3C(2)XnC(3)X3C(4)),
      however, allocates Sm-AMP-X to the recently acknowledged alpha-hairpinin family
      of plant defense peptides that share the helix-loop-helix fold stabilized by two
      disulfide bridges C(1)-C(4) and C(2)-C(3). Sm-AMP-X exhibits high broad-spectrum
      activity against fungal phytopathogens. We further showed that the N- and C
      terminal "tail" regions of the peptide are important for both its structure and
      activity. The truncated variants Sm-AMP-X1 with both disulfide bonds preserved
      and Sm-AMP-X2 with only the internal S-S-bond left were progressively less active
      against fungi and presented largely disordered structure as opposed to the
      predominantly helical conformation of the full-length antifungal peptide. cDNA
      and gene cloning revealed that Sm-AMP-X is processed from a unique multimodular
      precursor protein that contains as many as 12 tandem repeats of alpha-hairpinin
      like peptides. Structure of the sm-amp-x gene and two related pseudogenes sm-amp
      x-psi1 and sm-amp-x-psi2 allows tracing the evolutionary scenario that led to
      generation of such a sophisticated precursor protein. Sm-AMP-X is a new promising
      candidate for engineering disease resistance in plants. 

PMID- 24081692
TI  - Transcriptome-wide analysis of dynamic variations in regulation modes of
      grapevine microRNAs on their target genes during grapevine development.
AB  - MicroRNAs (miRNAs) play critical regulatory roles mainly through cleaving their
      target mRNAs or repressing gene translation during plant development. Grapevines
      are among the most economically important fruit crops with available whole genome
      sequences. Studies on grapevine miRNAs (Vv-miRNAs) are also widely available.
      However, studies on the regulation mode of Vv-miRNAs on their target mRNAs during
      grapevine development have not been studied well, especially at the transcriptome
      wide level. Here, six small RNA and mRNA libraries from various grapevine tissues
      were constructed for Illumina and Degradome sequencing. Subsequently, we
      systematically analyzed the spatiotemporal variations in the regulation of the
      target genes of regulation of Vv-miRNAs. In total, 242 known and 132 novel Vv
      miRNAs and 193 target mRNAs were identified, including 103 target mRNAs for known
      and 90 target mRNAs for novel miRNAs, were validated in one or more of the
      tissues examined. More than 50 % of novel miRNAs were expressed exclusively in
      the flowers and berries, where they cleaved their target genes in a tissue
      specific manner, especially, the breadth of their cleavage sites in flower
      tissues. Moreover, six novel miRNAs in berries responded to exogenous gibberellin
      and/or ethylene under a quantitative real time RT-PCR analysis, which confirmed
      their regulatory functions during berry development. Up to 93.6 % of the known
      miRNAs were highly conserved in various tissues, where their expression levels
      exhibited dynamic variations during grapevine development. Significantly, some Vv
      miRNA families had one key member that acted as the main regulator of their
      target genes during grapevine development. 

PMID- 24081694
TI  - The effects of Moufarrege total posterior pedicle reduction mammaplasty on
      breastfeeding: a review of 931 cases.
AB  - BACKGROUND: Since its original description in 1979, the Moufarrege total
      posterior pedicle reduction mammaplasty technique has proven to be a safe and
      reliable procedure providing aesthetic and functional enhancement. OBJECTIVES: To
      determine if the Moufarrege total posterior pedicle reduction mammaplasty affects
      successful breastfeeding. METHOD: Retrospective chart review was performed for
      patients operated on between 1981 and 1997, and a written questionnaire was
      given. Patients were asked about their ability to lactate and successfully
      breastfeed preoperatively and postoperatively. The t test and chi(2) test were
      used to compare means and categorical variables, respectively. Values were also
      compared with a sample of women (n = 2223) from the Quebec general population as
      collected by the Longitudinal Study of Child Development in Quebec (ELDEQ, 1998
      2002). RESULTS: A total of 931 patients (all women) underwent reduction
      mammaplasty during the study period at Jewish General Hospital, Montreal, Quebec,
      Canada (H.S.) or Hopital Hotel-Dieu, Montreal, Quebec, Canada (E.B. and R.M).
      There was a 62% response rate to the questionnaire. There were no statistically
      significant differences in the percentage of women able to lactate
      postoperatively vs preoperatively (98% vs 100%, respectively; P = .2). The
      percentage of women able to successfully breastfeed for 4 and 6 months was also
      not statistically different when comparing postoperative vs preoperative ability
      (4 months: 33% vs 44 %, P = .13; 6 months: 29% vs 28%, P = .77). The sample of
      women from the Quebec population did not differ statistically from those
      undergoing the Moufarrege breast reduction in terms of successful breastfeeding
      for 1, 2, 3, and 4 months (59% vs 67%, 52% vs 47%, 42% vs 41%, and 40% vs 33%,
      respectively). CONCLUSIONS: The Moufarrege breast reduction technique is a
      reliable and safe procedure that does not seem to negatively affect the success
      of breastfeeding based on the results of our retrospective chart review and
      patient questionnaire. LEVEL OF EVIDENCE: 4.

PMID- 24081693
TI  - Percutaneous fasciotomies and fat grafting: indications for breast surgery.
AB  - BACKGROUND: The management of breast deformities can be very difficult in the
      presence of breast shape retraction. Percutaneous fasciotomies, which release
      fibrous strings, can be a very useful tool for shape improvement in the recipient
      site for a fat graft. OBJECTIVES: The authors evaluate the efficacy of
      fasciotomies in association with fat grafting in breast surgery. METHODS: A
      retrospective chart review was conducted for 1000 patients treated with
      concurrent fasciotomies and fat grafting between January 2006 and December 2011.
      The recipient site was prepared with fasciotomies, and fat was harvested from
      other parts of the body using a low-pressure 10-mL syringe lipoaspiration system.
      Fat was centrifuged and injected into the breast for reconstruction or chest
      deformities. The postoperative appearance of the breast scars was scored by both
      the surgeon and the patient. Each complication was recorded, including instances
      of hematoma, infection, tissue wounds, scar healing, and fat necrosis. RESULTS:
      In this series of patients, for whom the primary indications for the procedure
      were sequelae of breast-conserving surgery after cancer, latissimus dorsi flap
      breast reconstruction, breast implant reconstruction, tuberous breast, Poland
      syndrome, and funnel chest, we recorded the following complications: 0.8% local
      infections (8/1000), 0.1% delayed wound healing that required medical care
      (1/1000), and 3% fat necrosis (31/1000). Fasciotomy scarring was considered minor
      by the patient in 98.5% of cases and by the surgeon in 99% of cases at 1 year
      postoperatively. CONCLUSIONS: Fat grafting is a safe and reliable technique that
      improves the aesthetic outcomes of breast surgery. Percutaneous fasciotomies
      provide excellent aesthetic results and an improvement in breast shape with no
      scarring. In our experience, both fat grafting and fasciotomies offer a durable
      result over the long term.

PMID- 24081695
TI  - Commentary on: An innovative procedure for the treatment of primary and recurrent
      capsular contracture (CC) following breast augmentation.

PMID- 24081697
TI  - Commentary on: Postoperative clitoral hood deformity after labiaplasty.

PMID- 24081696
TI  - Outpatient lipoabdominoplasty: review of the literature and practical
      considerations for safe practice.
AB  - BACKGROUND: Lipoabdominoplasty, popularized by Saldanha et al in 2001, is a
      powerful technique to contour the abdomen and flanks. It has not gained
      widespread use as concerns exist about increased complications related to wound
      healing and thromboembolism. OBJECTIVES: The authors review the existing
      literature on lipoabdominoplasty and discuss their experiences with the technique
      in a retrospective case series. METHODS: A literature search of PubMed/MEDLINE
      using the search terms lipoabdominoplasty and abdominoplasty was performed by 2
      independent investigators. The charts of 85 consecutive patients who underwent
      lipoabdominoplasty between February 2007 and July 2012 were reviewed. RESULTS: A
      combined 1316 lipoabdominoplasty patients had results reported in the literature.
      Of these patients, 21 of 1316 (1.6%) developed seroma, 5 of 1032 (0.5%)
      experienced hematoma, 6 of 1032 (0.6%) experienced venous thromboembolism, and 3
      of 1032 (0.3%) developed pulmonary embolism. In our case series, all patients
      were women with an average age of 48 years (range, 27-70 years), average body
      mass index of 25.2 (17.7-35.5), average follow-up of 8 months (range, 1-54
      months), average lipoaspirate of 1605 mL (range, 150-5350 mL), and average weight
      of resected tissue of 1039 g (range, 128-4838 g). The average operative time was
      225 minutes (range, 88-435 minutes), and average time in recovery prior to
      discharge was 124 minutes (range, 33-270 minutes). Seroma occurred in 20 of 85
      patients, 1 patient developed deep venous thrombosis (DVT), 1 patient developed
      cellulitis, and 1 patient developed an abscess. CONCLUSION: Lipoabdominoplasty is
      a safe and effective procedure in appropriately selected patients. Performing the
      procedure in an outpatient setting requires attention to multiple factors in the
      perioperative period to ensure safe patient outcomes. Larger prospective studies
      should be performed to evaluate best practices regarding rare complications such
      as DVT or pulmonary embolism.

PMID- 24081698
TI  - Commentary on: The effect of lipoaspirates cryopreservation on adipose-derived
      stem cells.

PMID- 24081699
TI  - The commercialization of plastic surgery.
AB  - The last decade has brought a major challenge to the traditional practice of
      plastic surgery from corporations that treat plastic surgery as a commercial
      product and market directly to the public. This corporate medicine model may
      include promotion of a trademarked procedure or device, national advertising that
      promises stunning results, sales consultants, and claims of innovation,
      superiority, and improved safety. This article explores the ethics of this
      business practice and whether corporate medicine is a desirable model for
      patients and plastic surgeons. 

PMID- 24081700
TI  - Commercialization: defining our terms.

PMID- 24081701
TI  - Injection lipolysis with phosphatidylcholine and deoxycholate.

PMID- 24081702
TI  - Response to "Injection lipolysis with phosphatidylcholine and deoxycholate".

PMID- 24081703
TI  - Response to "Injection lipolysis with phosphatidylcholine and deoxycholate".

PMID- 24081704
TI  - An inexpensive, fast, and easy way to harvest large volumes of adipose tissue for
      autologous grafting.

PMID- 24081705
TI  - Narratives can motivate environmental action: the Whiskey Creek ocean
      acidification story.
AB  - Even when environmental data quantify the risks and benefits of delayed responses
      to rapid anthropogenic change, institutions rarely respond promptly. We propose
      that narratives complementing environmental datasets can motivate responsive
      environmental policy. To explore this idea, we relate a case study in which a
      narrative of economic loss due to regionally rapid ocean acidification-an
      anthropogenic change-helped connect knowledge with action. We pose three
      hypotheses to explain why narratives might be particularly effective in linking
      science to environmental policy, drawing from the literature of economics,
      environmental policy, and cognitive psychology. It seems that yet-untold
      narratives may hold similar potential for strengthening the feedback between
      environmental data and policy and motivating regional responses to other
      environmental problems. 

PMID- 24081706
TI  - Nutrient removal and biomass production in an outdoor pilot-scale phototrophic
      biofilm reactor for effluent polishing.
AB  - An innovative pilot-scale phototrophic biofilm reactor was evaluated over a 5
      month period to determine its capacity to remove nitrogen and phosphorus from
      Dutch municipal wastewater effluents. The areal biomass production rate ranged
      between 2.7 and 4.5 g dry weight/m(2)/day. The areal nitrogen and phosphorus
      removal rates averaged 0.13 g N/m(2)/day and 0.023 g P/m(2)/day, which are low
      compared to removal rates achieved in laboratory biofilm reactors. Nutrient
      removal increased during the day, decreased with decreasing light intensity and
      no removal occurred during the night. Additional carbon dioxide supply was not
      requisite as the wastewater was comprised of enough inorganic carbon to sustain
      microalgal growth. The study was not conclusive for the limiting factor that
      caused the low nutrient removal rate, possibly the process was limited by light
      and temperature, in combination with pH increases above pH 9 during the daytime.
      This pilot-scale study demonstrated that the proposed phototrophic biofilm
      reactor is not a viable post-treatment of municipal wastewater effluents under
      Dutch climate conditions. However, the reactor performance may be improved when
      controlling the pH and the temperatures in the morning. With these adaptations, a
      phototrophic biofilm reactor could be feasible at lower latitudes with higher
      irradiance levels.

PMID- 24081707
TI  - The L-cell isolation from heterogonous population of intestinal cell line using
      antibiotic selection method.
AB  - Enteroendocrine cells are the largest population of hormone-producing cells in
      the body and play important roles in many aspects of body functions. The
      enteroendocrine cell population is divided into different subpopulations that
      secrete different hormones and peptides. Characterization of each subpopulation
      is particularly useful for analyzing the cellular mechanisms responsible for
      specific cell types. Therefore, the necessity of a pure cell line for a specific
      study purpose was the important motivation for the separation of cell lines for
      each subpopulation of enteroendocrine cells. The present research introduces a
      method for the isolation of L-cells, one of the important subpopulations of
      enteroendocrine cells. The antibiotic selection method was conducted in order to
      isolate the L-cells from a heterogonous population of intestinal cell line. In
      this method, a neomycin resistance gene (as selected marker) was expressed under
      the control of a specific promoter of L-cells. After transfection of manipulated
      plasmid, only the cells which determine the specific promoter and express
      neomycin resistance protein would be able to survive under Geneticin antibiotic
      treatment condition. In order to confirm that the isolated cells were L-cells,
      reverse transcriptase polymerase chain reaction (PCR) and quantitative PCR assays
      were performed. Based on the results, the isolated cells were pure L-cells that
      could be able to express specific mRNA of L-cells efficiently. This technique
      provides a unique method for the isolation and purification of any cell line. The
      purified isolated L-cells by this method can be used for future studies and for
      analyzing cellular mechanisms that involve L-cells' functions.

PMID- 24081708
TI  - Response surface methodology based optimization of beta-glucosidase production
      from Pichia pastoris.
AB  - The thermotolerant yeast Pichia etchellsii produces multiple cell bound beta
      glucosidases that can be used for synthesis of important alkyl- and aryl
      glucosides. Present work focuses on enhancement of beta-glucosidase I (BGLI)
      production in Pichia pastoris. In the first step, one-factor-at-a-time
      experimentation was used to investigate the effect of aeration, antifoam
      addition, casamino acid addition, medium pH, methanol concentration, and mixed
      feed components on BGLI production. Among these, initial medium pH, methanol
      concentration, and mixed feed in the induction phase were found to affect BGLI
      production. A 3.3-fold improvement in beta-glucosidase expression was obtained at
      pH 7.5 as compared to pH 6.0 on induction with 1 % methanol. Addition of
      sorbitol, a non-repressing substrate, led to further enhancement in beta
      glucosidase production by 1.4-fold at pH 7.5. These factors were optimized with
      response surface methodology using Box-Behnken design. Empirical model obtained
      was used to define the optimum "operating space" for fermentation which was a pH
      of 7.5, methanol concentration of 1.29 %, and sorbitol concentration of 1.28 %.
      Interaction of pH and sorbitol had maximum effect leading to the production of
      4,400 IU/L. The conditions were validated in a 3-L bioreactor with accumulation
      of 88 g/L biomass and 2,560 IU/L beta-glucosidase activity.

PMID- 24081710
TI  - A case of acute traumatic subdural hematoma in a child with previous bilateral
      encephaloduroarteriosynangiosis.
AB  - The authors report the case of a 5-year-old female with right-sided hemiparesis
      and aphasia secondary to moyamoya disease, who had previously undergone staged
      bilateral encephaloduroarteriosynangiosis procedures. A subsequent ground-level
      fall caused an acute traumatic subdural hematoma with mass effect and
      neurological decline. She underwent emergency hematoma evacuation and
      decompressive craniectomy, which required interruption of the superficial
      temporal artery that had been used for indirect bypass, followed later by
      autologous cranioplasty. There were no acute or long-term ischemic events related
      to the occurrence or treatment of the traumatic hematoma. Follow-up angiography
      revealed extensive spontaneous vascular collateralization in the field of the
      decompressive craniectomy and cranioplasty. The patient returned to her pre
      injury neurological baseline. 

PMID- 24081709
TI  - Isolation and bioinformatic analysis of a novel transposable element, ISCbe4,
      from the hyperthermophilic bacterium, Caldicellulosiruptor bescii.
AB  - Caldicellulosiruptor bescii is an anaerobic thermophilic bacterium of special
      interest for use in the consolidated bioprocessing of plant biomass to biofuels.
      In the course of experiments to engineer pyruvate metabolism in C. bescii, we
      isolated a mutant of C. bescii that contained an insertion in the L-lactate
      dehydrogenase gene (ldh). PCR amplification and sequencing of the ldh gene from
      this mutant revealed a 1,609-bp insertion that contained a single open reading
      frame of 479 amino acids (1,440 bp) annotated as a hypothetical protein with
      unknown function. The ORF is flanked by an 8-base direct repeat sequence.
      Bioinformatic analysis indicated that this ORF is part of a novel transposable
      element, ISCbe4, which is only intact in the genus Caldicellulosiruptor, but has
      ancient relatives that are present in degraded (and previously unrecognized)
      forms across many bacterial and archaeal clades. 

PMID- 24081711
TI  - Functional mullerian tissue within the conus medullaris generating cyclical
      neurological morbidity in an otherwise healthy female.
AB  - PURPOSE: Endometriosis is a common disease; however, ectopic mullerian tissue
      within the spine is a rare entity with the potential for producing significant
      neurological compromise. There are several postulated etiologies for this
      phenomenon, and only a few case reports are available in the world literature.
      Knowledge of this rare phenomenon is of paramount importance, since early
      diagnosis can lead to lessened neurological morbidity. METHODS: In this
      manuscript, we present a case report, discuss gynecological and neurosurgical
      perspectives relating to the treatment strategies for managing this entity, and
      propose an alternative explanation for such an occurrence from a neurogenetic
      standpoint. RESULTS: We present a case of spinal mullerianosis within the conus
      medullaris which was managed symptomatically for several years with an
      intracystic drain and subcutaneous reservoir. Over the years, it became clear
      that there was a cyclical presentation to her clinical malady, which at times was
      severe. Ultimately, she required surgical resection which aided in her diagnosis
      and subsequent treatment. CONCLUSION: Intraspinal mullerianosis is a rare
      location for an otherwise common disease in women and has the potential to create
      significant neurological morbidity by creating a mass lesion. Although the exact
      etiology remains unclear, the histogenic theories of embryologic origin appear
      most plausible. Treatment strategies for this condition may include hormonal
      therapy, obstetrical surgery, or open spinal surgery. This unusual and poorly
      understood disease should be considered in the differential diagnosis for
      intraspinal lesions presenting with hemorrhage in the clinical context of
      cyclical neurological symptoms.

PMID- 24081712
TI  - Intraventricular migration of ventricular access device.

PMID- 24081713
TI  - Death rate from hip replacement almost halved in eight years.

PMID- 24081714
TI  - Weight changes during inpatient refeeding of underweight eating disorder
      patients.
AB  - AIM: To describe patterns of weight change in patients admitted to a specialised
      eating disorder program with established protocols for inpatient refeeding.
      METHODS: Weight records between January 2000 and December 2006 were categorised
      using Body Mass Index (BMI) at first admission (BMI ranges < 14.0, 14.1-17.49,
      17.5-18.9 kg/m(2)). Total weight gained, number of days of inpatient treatment
      and rate of weekly weight gain were examined. RESULTS: In total there were 247
      patients representing 414 admissions. The rate of weight gain was 0.77, 0.63 and
      0.53 kg/week, respectively, for each BMI group. Twenty patients (8.1%) in the
      refeeding program did not gain weight. CONCLUSION: Weight gain in underweight
      patients is highly variable. A greater understanding of the processes that
      contribute to weight gain, and establishment of best practice in achieving weight
      gain in patients needs to be determined. This data provide detailed information
      about expectations for refeeding without artificial feeding.

PMID- 24081715
TI  - Effectiveness of self-esteem and social skills group therapy in adolescent eating
      disorder patients attending a day hospital treatment programme.
AB  - OBJECTIVE: To evaluate self-esteem and social skills in adolescent eating
      disorder patients before and after specific group therapy as part of a Day
      Hospital Programme. METHOD: One hundred and sixty adolescent eating disorder
      patients, classified as anorexia nervosa and related disorders (AN-rd) (N = 116)
      or bulimia nervosa and related disorders (BN-rd) (N = 44) received structured
      group therapy for developing self-esteem and social skills. RESULTS: BN-rd
      patients had poorer perceptions of some self-esteem and social skills variables.
      After group therapy, both groups presented significant improvements in their
      perceptions of physical appearance, their self-concept related to weight and
      shape and to others, happiness and satisfaction, social withdrawal and
      leadership. BN-rd patients presented more changes on many of the variables.
      DISCUSSION: Specific self-esteem and social skills group therapy in patients with
      eating disorders can be useful in improving certain core features.

PMID- 24081716
TI  - Why are we waiting? The relationship between low admission weight and end of
      treatment weight outcomes.
AB  - Inpatient eating disorder units are increasingly being asked to admit patients at
      lower BMI's, often delaying hospital treatment until medically unavoidable. This
      paper aims to explore the impact of this trend on treatment outcome. Eighty-two
      adults with anorexia nervosa admitted to a national inpatient eating disorder
      ward were assessed for BMI at admission, length of hospitalisation, discharge BMI
      and re-admission within 1-year post-treatment. In the current study, admission
      BMI was unrelated to amount of weight gain during treatment or to length of
      hospital stay. As such patients admitted at lower BMI's had significantly lower
      BMI's on discharge from treatment. Low admission BMI's were related to
      significantly higher likelihoods of re-admission within 1 year. This study
      provides strong evidence for the benefit of early treatment episodes and with
      more successful treatment outcomes being related to higher weights at start of
      treatment.

PMID- 24081717
TI  - What are the top five essential features of a high quality eating disorder
      service? A comparison of the views of US and UK eating disorder sufferers, carers
      and health professionals.
AB  - OBJECTIVE: The aim of the present study was to identify what are the main
      features of a high quality eating disorders service and to triangulate the views
      of patients, carers and health professionals in a cross-national (USA, UK)
      survey. METHODS: Data from an internet survey were subjected to content analysis
      and common themes were identified. RESULTS: All six stakeholder groups (US and UK
      patients, carers and health professionals) included the professional qualities of
      staff amongst their top five quality features. Personal qualities of staff,
      support for carers and psychological interventions were mentioned by four of the
      six groups, Support for service users and nutritional assistance was mentioned by
      three groups. Availability/access and Rapid access to care were mentioned by UK
      Carers and UK health care personnel. Medical assistance was only mentioned by US
      health care professionals and flexible care only by UK sufferers. CONCLUSION:
      This study suggests many similarities and some differences between different
      stakeholders from two countries with different health care systems in their views
      on quality of care.

PMID- 24081718
TI  - Emotion and eating in binge eating disorder and obesity.
AB  - This study compares 20 binge eaters (BED), 23 obese patients (OB) and 20 normal
      weight controls (CO) with regard to everyday emotions and the relationship
      between emotions, the desire to eat and binge eating. Modified versions of the
      Differential Affect Scale and Emotional Eating Scale were used and the TAS-20 and
      Symptom-Check-List-27 administered to assess overall psychopathology and
      alexithymia. BED-subjects show a more negative pattern of everyday emotions,
      higher alexithymia scores and the strongest desire to eat, especially if emotions
      are linked to interpersonal aspects. The emotion most often reported preceding a
      binge was anger. Feelings of loneliness, disgust, exhaustion or shame lead to
      binge eating behaviour with the highest probability.

PMID- 24081719
TI  - Role of media and peers on body change strategies among adult men: is body size
      important?
AB  - There has been limited previous research that has examined the role of
      sociocultural influences on body change strategies among adult men. The current
      study investigated the role of specific types of messages (encouragement, teasing
      and modelling) from peers and the media on the strategies to change weight among
      adult men. Differences were evaluated between 526 men aged from 18 to 60 years
      from three groups (normal weight, overweight and obese) on body image, body
      change strategies and messages about their body received from peers and the
      media. Men were primarily drawn from United States, Australia and Europe. Results
      showed that messages received by men regarding losing weight or increasing muscle
      size differed according to weight. Body image and media messages were the
      strongest predictors of losing weight, whereas body image importance and messages
      from peers were the strongest predictors of increasing muscles. These findings
      highlight the importance of sociocultural influences on body change strategies
      among adult males.

PMID- 24081720
TI  - [Lung infarction - a diagnostic challenge in the oncologic patient?].

PMID- 24081721
TI  - ["Licensures (approbations) of Jewish physicians expire 30 September 1938" - 75
      years ago the NS legislature withdrew the state professional permits of
      physicians].

PMID- 24081722
TI  - [Invitation to the Annual Congress of the German Society of Neuroradiology].

PMID- 24081723
TI  - [Mandatory application requirement - approval requirement of services in
      accordance with radiation diagnosis and therapy agreement].

PMID- 24081726
TI  - Automatic needle detection and tracking in 3D ultrasound using an ROI-based
      RANSAC and Kalman method.
AB  - This article proposes a robust technique for needle detection and tracking using
      three-dimensional ultrasound (3D US). It is difficult for radiologists to detect
      and follow the position of micro tools, such as biopsy needles, that are inserted
      in human tissues under 3D US guidance. To overcome this difficulty, we propose a
      method that automatically reduces the processed volume to a limited region of
      interest (ROI), increasing at the same time the calculation speed and the
      robustness of the proposed technique. First, a line filter method that enhances
      the contrast of the needle against the background is used to facilitate the
      initialization of ROI using the tubularness information of the complete US
      volume. Then, the random sample consensus (RANSAC) and Kalman filter (RK)
      algorithm is used in the ROI to detect and track the precise position of the
      needle. A series of numerical inhomogeneous phantoms with a needle simulated from
      real 3D US volumes are used to evaluate our method. The results show that the
      proposed method is much more robust than the RANSAC algorithm when detecting the
      needle, regardless of whether or not the insertion axis corresponds to an
      acquisition plane in the 3D US volume. The possibility of failure is also
      discussed in this article. 

PMID- 24081725
TI  - Compromised visceral circulation does not affect the outcome of colorectal
      surgery.
AB  - PURPOSE: Anastomotic leakage is a serious complication after colorectal surgery,
      and many risk factors for this problem have so far been identified. The aim of
      this study was to assess the association between visceral arterial occlusive
      disease and anastomotic leakage. METHODS: The preoperative abdominal computed
      tomography scans from all consecutive patients who underwent colorectal surgery
      with anastomosis in 2010 were retrospectively analyzed. RESULTS: A total of 242
      patients were included, with a median age of 65 years (interquartile range 55
      74). Anastomotic leakage occurred in 14 % of cases (n = 34). The mortality rate
      was 3 % (n = 8). There was no association between atherosclerosis of the visceral
      or iliac arteries and anastomotic leakage. There was also no association between
      right-sided or left-sided resections and total occlusion of the superior or
      inferior mesenteric artery, respectively. CONCLUSION: Asymptomatic visceral
      artery occlusive disease is not a risk factor for anastomotic leakage after
      colorectal surgery, and additional radiological imaging or percutaneous
      transluminal angioplasty for occluded visceral vessels is not indicated prior to
      colorectal surgery.

PMID- 24081727
TI  - Three-dimensional evaluation of masseter muscle in different vertical facial
      patterns: a cross-sectional study in growing children.
AB  - The aim of the present study was to analyze the anatomical three-dimensional (3D)
      characteristics of masseter muscle in growing subjects with different vertical
      patterns by using an ultrasound (US) method. The sample comprised 60 prepuberal
      subjects (33 males, 27 females) with a mean age of 11.5 +/- 1.6 years with late
      mixed or permanent dentition and Class I molar and skeletal relationship. For
      each subject, a lateral cephalogram was required, and according to the mandibular
      plane angle (Frankfort horizontal plane/mandibular plane angle [FMA]), the
      subjects were divided into three groups of different underlying vertical facial
      patterns: brachyfacial: FMA < 22 degrees , mesofacial: 22 degrees  <= FMA <= 28
      degrees , and dolichofacial: FMA > 28 degrees . For each subject, an US scan was
      carried out to analyze the width, the thickness, the cross-sectional area, and
      the volume of the masseter muscle. Mean differences in measurements between
      vertical facial subgroups were contrasted by means of analysis of variance
      (ANOVA) with Tukey's post hoc tests (p < 0.05). Measurements of the whole
      masseter in dolichofacial patients were significantly smaller when compared with
      brachyfacial and mesofacial individuals during relaxation and contraction. The
      volume of the masseter decreased significantly by 10% going from the brachyfacial
      group to the mesofacial group and from the mesofacial group to the dolichofacial
      group with no difference between the left and the right sides. A significant
      negative correlation was found between the US measurements and the divergency
      (FMA degrees ). Ultrasound is a technique indicated in children for evaluating
      muscles of mastication in vivo. Growing patients with a dolichofacial vertical
      pattern present with a reduced dimension of the masseter when compared with
      brachyfacial and mesofacial subjects. 

PMID- 24081728
TI  - Intraoperative cardiac ultrasound examination using vector flow imaging.
AB  - Conventional ultrasound (US) methods for blood velocity estimation only provide
      one-dimensional and angle-dependent velocity estimates; thus, the complexity of
      cardiac flow has been difficult to measure. To circumvent these limitations, the
      Transverse Oscillation (TO) vector flow method has been proposed. The vector flow
      method implemented on a commercial scanner provided real-time, angle-independent
      estimates of cardiac blood flow. Epicardiac and epiaortic, intraoperative US
      examinations were performed on three patients with stenosed coronary arteries
      scheduled for bypass surgery. Repeating cyclic beat-to-beat flow patterns were
      seen in the ascending aorta and pulmonary artery of each patient, but these
      patterns varied between patients. Early systolic retrograde flow filling the
      aortic sinuses was seen in the ascending aorta as well as early systolic
      retrograde flow in the pulmonary artery. In diastole, stable vortices in aortic
      sinuses of the ascending aorta created central antegrade flow. A stable vortex in
      the right atrium was seen during the entire heart cycle. The measurements were
      compared with estimates obtained intraoperatively with conventional spectral
      Doppler US using a transesophageal and an epiaortic approach. Mean differences in
      peak systole velocity of 11% and 26% were observed when TO was compared with
      transesophageal echocardiography and epiaortic US, respectively. In one patient,
      the cardiac output derived from vector velocities was compared with pulmonary
      artery catheter thermodilution technique and showed a difference of 16%. Vector
      flow provides real-time, angle-independent vector velocities of cardiac blood
      flow. The technique can potentially reveal new information of cardiovascular
      physiology and give insight into blood flow dynamics. 

PMID- 24081729
TI  - Rapid breast density analysis of partial volumes of automated breast ultrasound
      images.
AB  - Rapid volume density analysis (RVDA) for automated breast ultrasound (ABUS) has
      been proposed as a more efficient method for estimating breast density. In the
      current experiment, ABUS images were obtained for 67 breasts from 40 patients.
      For each case, three rectangular volumes of interest (VOIs) were extracted,
      including the VOIs located at the 6 and 12 o'clock positions relative to the
      nipple in the anterior to posterior pass and the lateral position relative to the
      nipple in the lateral pass. The centers of these VOIs were defined to align with
      the center of nipple, and the depths reached the retromammary fat boundary. The
      fuzzy c-means classifier was applied to differentiate the fibroglandular and fat
      tissues to estimate the density. The classification results of the three VOIs
      were averaged to obtain the breast density. The density correlations between the
      RVDA and the ABUS methods were 0.98 and 0.96 using Pearson's correlation and
      linear regression coefficients, respectively. The average computation times for
      RVDA and ABUS were 4.2 and 17.8 seconds, respectively, using an Intel Core2 2.66
      GHz computer with 3.25 GB memory. In conclusion, the RVDA method offers a
      quantitative and efficient breast density estimation for ABUS.

PMID- 24081730
TI  - Gestational diabetes and type 2 diabetes in reproductive-aged women with
      polycystic ovary syndrome.
AB  - CONTEXT: Polycystic ovary syndrome (PCOS) affects 6%-21% of women. PCOS has been
      associated with an increased risk of dysglycemia including gestational diabetes
      mellitus (GDM) and type 2 diabetes mellitus (T2DM). OBJECTIVE: The objective of
      the study was to assess the prevalence of dysglycemia and the impact of obesity
      in young reproductive-aged women with and without PCOS in a community-based
      cohort. DESIGN: This was a cross-sectional analysis of data from a large
      longitudinal study (the Australian Longitudinal Study on Women's Health).
      SETTING: The setting for the study was the general community. PARTICIPANTS: Women
      were randomly selected from the national health insurance database. Standardized
      data collection occurred at five survey time points (years 1996, 2000, 2003,
      2006, and 2009). Data from survey 4 (2006, n = 9145, 62% of original cohort aged
      18-23 y) were examined for this study. MAIN OUTCOME MEASURES: Self-reported PCOS,
      GDM, and T2DM were measured. RESULTS: In women aged 28-33 years, PCOS prevalence
      was 5.8% [95% confidence interval (CI) 5.3%-6.4%]. The prevalence of GDM (in
      women reporting prior pregnancy) and T2DM was 11.2% and 5.1% in women with PCOS
      and 3.8% and 0.3% in women without PCOS, respectively (P for both < .001). PCOS
      was associated with an increased odds of GDM and T2DM. After adjusting for age,
      body mass index, hypertension, smoking, and demographic factors, the odds of GDM
      (odds ratio 2.1, 95% CI 1.1-3.9, P = .02) and T2DM (odds ratio 8.8, 95% CI 3.9
      20.1, P < .001) remained increased in women reporting PCOS. CONCLUSIONS: In a
      large community-based cohort of reproductive-aged women, PCOS was independently
      associated with a higher risk of GDM and T2DM, independent of body mass index.
      Aggressive screening, prevention, and management of dysglycemia is clearly
      warranted in women with PCOS.

PMID- 24081731
TI  - Comparative effectiveness of osteoporosis drugs in preventing secondary
      nonvertebral fractures in Taiwanese women.
AB  - CONTEXT: The evidence for relative effectiveness of osteoporosis drugs in
      secondary prevention of nonvertebral fractures was unclear and could not be
      extrapolated to the Asian population. OBJECTIVE: The objective of the study was
      to compare the relative effectiveness of different classes of osteoporosis drugs
      in secondary prevention of nonvertebral fractures in Taiwanese women. DESIGN:
      This was a retrospective cohort study from 2003 to 2007, with up to 6 years of
      follow-up. SETTING: The study included enrollees in Taiwan National Health
      Insurance. PATIENTS: Patients older than 50 years, with vertebral/hip fracture
      and were new to osteoporosis therapy, were recruited. INTERVENTION: Patients were
      classified into the alendronate, calcitonin, or raloxifene group, according to
      their exposure after follow-up. MAIN OUTCOME MEASURE: The primary outcome of our
      study was the risk of incident nonvertebral fracture (hip, humerus, or radius
      fractures). A multivariate Cox proportional hazard model adjusted for fracture
      risk factors was used to compare the relative fracture risk among three treatment
      groups under on-treatment scenarios. Propensity score-matched hazard ratios were
      examined, and interactions between fracture incidence and patients' compliance
      were investigated as well. RESULTS: There were 19 840, 9534, and 25 483 patients
      in the alendronate, raloxifene, and calcitonin groups, respectively. The fracture
      rates were highest in calcitonin recipients (4.57 per 100 person-years), followed
      by raloxifene and alendronate. Results from Cox analyses showed raloxifene
      (hazard ratio 1.47; 95% confidence interval 1.29-1.67) and calcitonin (hazard
      ratio 1.51; 95% confidence interval 1.29-1.75) had higher nonvertebral fracture
      risks as compared with alendronate. The risk differences were more pronounced in
      compliant patients. CONCLUSION: We found alendronate users had the lowest
      secondary nonvertebral fracture risk, as compared with raloxifene and calcitonin
      users. Consistent results were found in a series of sensitivity analyses.

PMID- 24081732
TI  - Progression of vertebral fractures despite long-term biochemical control of
      acromegaly: a prospective follow-up study.
AB  - BACKGROUND: In active acromegaly, pathologically elevated GH and IGF-1 levels are
      associated with increased bone turnover and a high bone mass, the latter being
      sustained after normalization of GH values. In a cross-sectional study design, we
      have previously reported a high prevalence of vertebral fractures (VFs) of about
      60% in patients with controlled acromegaly, despite normal mean bone mineral
      density (BMD) values. Whether these fractures occur during the active acromegaly
      phase or after remission is achieved is not known. OBJECTIVE: Our objective was
      to study the natural progression of VFs and contributing risk factors in patients
      with controlled acromegaly over a 2.5-year follow-up period. METHODS: Forty-nine
      patients (mean age 61.3 +/- 11.1 years, 37% female) with controlled acromegaly
      for >= 2 years after surgery, irradiation, and/or medical therapy and not using
      bisphosphonates were included in the study. Conventional spine radiographs
      including vertebrae Th4-L4 were assessed for VFs according to the Genant method.
      VF progression was defined as development of new/incident fractures and/or a
      minimum 1-point increase in the Genant scoring of preexisting VFs. BMD was
      assessed by dual-energy x-ray absorptiometry (Hologic 4500). RESULTS: Prevalence
      of baseline VFs was 63%, being highest in men, and fractures were unrelated to
      baseline BMD. VF progression was documented in 20% of patients, especially in men
      and in case of >= 2 VFs at baseline. VF progression was not related to BMD values
      or BMD changes over time. CONCLUSION: Findings from this longitudinal study show
      that VFs progress in the long term in 20% of patients with biochemically
      controlled acromegaly in the absence of osteoporosis or osteopenia. These data
      suggest that an abnormal bone quality persists in these patients after remission,
      possibly related to pretreatment long-term exposure to high circulating levels of
      GH.

PMID- 24081733
TI  - Hypothalamic-pituitary-adrenal axis recovery following prolonged prednisolone
      therapy in infants.
AB  - CONTEXT: The duration of hypothalamic-pituitary-adrenal (HPA) axis suppression
      after glucocorticoid treatment is uncertain. OBJECTIVE: We aimed to determine the
      duration of HPA axis suppression in prednisolone-treated infants and the age at
      which circadian variation in salivary cortisol is established in healthy infants.
      DESIGN, SETTING, AND PARTICIPANTS: Before the adoption of propranolol treatment
      by the Vascular Birthmarks Clinic, 12 infants with infantile hemangioma received
      high-dose prednisolone for 12 to 25 weeks' duration, weaned over 4 to 6 weeks,
      and ceased at age 21 to 31 weeks. Parents collected serial salivary samples at
      two time points per day (before first and last feed) until circadian variation in
      salivary cortisol (measured by radioimmunoassay) was observed, when a
      confirmatory 1 MUg Synacthen test was performed. Ten healthy control infants had
      serial salivary cortisol measurements to determine the age at which circadian
      variation is established. MAIN OUTCOME MEASURE: We defined circadian variation as
      evening salivary cortisol <50% of the early morning level on two consecutive
      sampling weeks. RESULTS: Circadian variation appeared within 6 weeks (median 2.7,
      range 1.4-5.4) of prednisolone cessation. All confirmatory Synacthen tests were
      normal (peak serum cortisol >600 nmol/L) and were performed within 12 weeks of
      prednisolone cessation. Healthy controls developed circadian variation at median
      16 weeks of age (range 8-24). CONCLUSION: HPA recovery occurred within 6 to 12
      weeks, shorter than empirical recommendations, to give stress cover for 6 to 12
      months. Reduced duration of stress-cover precautions may reduce parental anxiety
      and side effects from unnecessary glucocorticoid use. Healthy control infants
      established circadian variation in salivary cortisol between 2 and 6 months of
      age.

PMID- 24081734
TI  - Update in adrenocortical carcinoma.
AB  - Adrenocortical carcinoma (ACC) is an orphan malignancy that has attracted
      increasing attention during the last decade. Here we provide an update on
      advances in the field since our last review published in this journal in 2006.
      The Wnt/beta-catenin pathway and IGF-2 signaling have been confirmed as
      frequently altered signaling pathways in ACC, but recent data suggest that they
      are probably not sufficient for malignant transformation. Thus, major players in
      the pathogenesis are still unknown. For diagnostic workup, comprehensive hormonal
      assessment and detailed imaging are required because in most ACCs, evidence for
      autonomous steroid secretion can be found and computed tomography or magnetic
      resonance imaging (if necessary, combined with functional imaging) can
      differentiate benign from malignant adrenocortical tumors. Surgery is potentially
      curative in localized tumors. Thus, we recommend a complete resection including
      lymphadenectomy by an expert surgeon. The pathology report should demonstrate the
      adrenocortical origin of the lesion (eg, by steroidogenic factor 1 staining) and
      provide Weiss score, resection status, and quantitation of the proliferation
      marker Ki67 to guide further treatment. Even after complete surgery, recurrence
      is frequent and adjuvant mitotane treatment improves outcome, but uncertainty
      exists as to whether all patients benefit from this therapy. In advanced ACC,
      mitotane is still the standard of care. Based on the FIRM-ACT trial, mitotane
      plus etoposide, doxorubicin, and cisplatin is now the established first-line
      cytotoxic therapy. However, most patients will experience progress and require
      salvage therapies. Thus, new treatment concepts are urgently needed. The ongoing
      international efforts including comprehensive "-omic approaches" and next
      generation sequencing will improve our understanding of the pathogenesis and
      hopefully lead to better therapies. 

PMID- 24081735
TI  - Identification of AP2S1 mutation and effects of low calcium formula in an infant
      with hypercalcemia and hypercalciuria.
AB  - CONTEXT: Although AP2S1 has recently been shown to be a causative gene for
      familial hypocalciuric hypercalcemia type 3 (FHH3), knowledge about FHH3 remains
      poor. OBJECTIVE: Our objective was to report AP2S1 mutation and effects of low
      calcium formula in a patient with hypercalcemia and hypercalciuria. PATIENT: This
      Japanese female infant was found to have hypercalcemia by a routine laboratory
      test for poor weight gain on breast feeding. At 49 days of age, serum calcium
      (adjusted by Payne's formula) was 13.1 mg/dL, intact PTH 27 pg/mL, and urinary
      calcium-to-creatinine ratio 1.29 mg/mg. There was no evidence for
      hyperparathyroidism, PTHrP-producing neoplasm, and vitamin D excess. These data,
      except for hypercalciuria, appeared to be consistent with defective calcium
      sensing receptor-mediated signaling. With use of low calcium formula containing
      2.6 mg/dL of calcium, she showed catch-up growth, and serum calcium was
      decreased, as was urinary calcium-to-creatinine ratio. Furthermore, feeding with
      a mixture of low calcium formula and standard formula with a 2:1 ratio maintained
      serum calcium ~12 mg/dL without markedly increasing serum PTH. RESULTS: Although
      no pathologic mutation was detected in CASR or GNA11, a presumably de novo
      heterozygous mutation (p.Arg15Leu), a previously reported causative mutation for
      FHH3, was identified in AP2S1 of this patient. CONCLUSIONS: The results imply
      that lack of hypocalciuria does not necessarily argue against the presence of
      AP2S1 mutations. The early infantile age of this patient would have played a
      certain role in the occurrence of hypercalciuria, and low calcium formula is
      worth attempting in infants with FHH.

PMID- 24081736
TI  - The role of proinsulin and insulin in the diagnosis of insulinoma: a critical
      evaluation of the Endocrine Society clinical practice guideline.
AB  - CONTEXT: An end of fast insulin >= 3 MUIU/mL and a proinsulin concentration >= 5
      pmol/L have been suggested as useful cutoffs for the diagnosis of insulinoma.
      OBJECTIVE: The main objective was to evaluate the diagnostic performance of an
      end of fast insulin concentration >= 3 MUIU/mL and an end of fast proinsulin
      concentration >= 5 pmol/L. DESIGN: The design was a case-control series. SETTING:
      The setting was a tertiary-care center. PATIENTS: Fifty-six subjects with a
      positive 48-hour supervised fast had an insulinoma between June 2000 and April
      2011. During this same time period, a diagnosis of insulinoma was excluded in 29
      subjects who underwent a supervised fast. INTERVENTION: 48-hour supervised fast.
      MAIN OUTCOME MEASURE: The main outcome measures were serum insulin concentration
      and plasma proinsulin concentration. RESULTS: Ninety-one percent of the patients
      with an insulinoma had a measured insulin concentration >=5 MUIU/mL at the end of
      fast. The sensitivity increased to 98% if the threshold to define inadequate
      insulin suppression was lowered to >=3 MUIU/mL. The median (interquartile range)
      end of fast proinsulin was 100 (53-270) pmol/L for cases and 6.8 (4.2-12.0)
      pmol/L for controls. An end of fast proinsulin value of >= 5 pmol/L could not
      distinguish cases from controls (59% false positive rate). All patients with an
      insulinoma (sensitivity 100%) and none of the control subject (specificity 100%)
      had end of fast proinsulin concentration >= 27 pmol/L. CONCLUSIONS: Using a
      current insulin assay 9% of insulinoma cases end the supervised fast with an
      insulin concentration below 5 MUIU/mL. Inadequate insulin suppression defined
      using a threshold of >= 3 MUIU/mL increases the sensitivity of the test. The
      value of the proinsulin test lies in its unique ability to distinguish cases from
      controls. A proinsulin concentration of >=22 pmol/L best discriminates cases from
      controls. Reliance on an end of fast proinsulin cutoff value of 5 pmol/L does not
      augment sensitivity but greatly reduces specificity of the test.

PMID- 24081737
TI  - Endurance training modulates intramyocellular lipid compartmentalization and
      morphology in skeletal muscle of lean and obese women.
AB  - CONTEXT: The accumulation of intramyocellular lipids (IMCLs) and mitochondrial
      dysfunction in skeletal muscle have been associated with insulin resistance in
      obesity. Endurance training (ET) increases mitochondrial content/activity and
      IMCL content in young, active men and women. We have previously shown that ET
      alters the size, number, and physical juxtaposition of IMCLs and mitochondria.
      OBJECTIVE: The purpose of this study was to determine the effects of obesity and
      ET on mitochondrial function, IMCL content, and IMCL-mitochondria juxtaposition
      in sedentary lean and obese women. DESIGN, SETTING, SUBJECTS, INTERVENTION, AND
      MAIN OUTCOME MEASURES: Obese (n = 11) and lean (n = 12), sedentary women were
      recruited using local advertisements and underwent 12 weeks of ET in our training
      facility at McMaster University. Blood and muscle biopsy samples (vastus
      lateralis) were collected before and after ET to measure IMCL and mitochondrial
      ultrastructure, mitochondrial oxidative capacity, lipid oxidation capacity, and
      lipid metabolism by-products. RESULTS: Obese women were insulin resistant
      (homeostasis model assessment of insulin resistance) compared with lean women. ET
      did not change body weight but increased mitochondrial oxidative and beta
      oxidation capacity in both groups. ET mediated reorganization of the muscle
      architecture, whereby IMCL content in the subsarcolemmal region was reduced with
      a concomitant increase in intermyofibrillar IMCLs. ET increased the percentage of
      IMCLs in direct contact with mitochondria and did not alter diacylglycerol and
      ceramide content in either group. CONCLUSIONS: ET mediated positive changes in
      mitochondrial function and lipid oxidation and induced intracellular IMCL
      reorganization, which is reflective of greater IMCL turnover capacity in both
      lean and obese women.

PMID- 24081738
TI  - 17beta-Estradiol and estradiol fatty acyl esters and estrogen-converting enzyme
      expression in adipose tissue in obese men and women.
AB  - CONTEXT: Obesity is associated with increased circulating 17beta-estradiol (E2),
      but less is known about E2 concentrations in adipose tissue. In addition to E2,
      adipose tissue synthesizes E2 fatty acyl esters (E2-FAE). OBJECTIVE: The aim was
      to compare estrogen concentrations and expression of estrogen-converting enzymes
      in adipose tissue between severely obese men and women. DESIGN AND SETTING:
      Tissue samples were obtained during elective surgery in University Central
      Hospital in the years 2008 through 2011. PATIENTS: We studied 14 men and 22
      premenopausal women undergoing bariatric surgery and 10 control women operated
      for nonmalignant reasons. INTERVENTIONS: Paired samples were taken from abdominal
      sc and visceral adipose tissue and serum and analyzed for E2 and E2-FAE by
      fluoroimmunoassay and liquid chromatography-tandem mass spectrometry. mRNA
      expression of genes was analyzed by quantitative PCR. RESULTS: Compared with men,
      E2 levels in sc adipose tissue in obese women were higher, along with higher
      relative mRNA expression of steroid sulfatase and 17beta-hydroxysteroid
      dehydrogenases 1, 7, and 12. In men, E2-FAE concentrations in adipose tissue were
      similar to E2 but in women significantly lower compared with E2. Adipose tissue
      E2-FAE and serum E2-FAE levels correlated positively in obese subjects. Serum E2
      did not significantly correlate with E2 concentration or mRNA expression of genes
      in adipose tissue in obese men or women. CONCLUSIONS: The production of E2 by the
      large adipose mass was not reflected by increased circulating E2 concentrations
      in severely obese men or women. However, adipose tissue may contribute to
      concentrations of serum E2-FAE.

PMID- 24081739
TI  - Overfeeding over 24 hours does not activate brown adipose tissue in humans.
AB  - CONTEXT: Human brown adipose tissue (BAT) is activated with cold exposure, but it
      is unknown whether overfeeding activates BAT. OBJECTIVE: We determined BAT
      activation with cold, fasting, and overfeeding and the relationship of BAT
      activation with future weight change. DESIGN, SETTING, PARTICIPANTS, AND
      INTERVENTIONS: Sixteen healthy adults were evaluated during energy balance,
      fasting, and 24 hours of 200% overfeeding. All subjects had a fluorodeoxyglucose
      positron emission tomography (PET) scan after exposure to 16 degrees C to
      determine cold-induced BAT activity (CIBA). The first six subjects had a second
      PET scan after 36 hours of fasting to establish the lack of BAT activation at 22
      degrees C. The other subjects' second PET scan occurred after 24 hours of
      overfeeding at 22 degrees C but only if they demonstrated CIBA. Twelve subjects
      returned at 6 months for reassessment of body composition. MAIN OUTCOME MEASURES:
      BAT was defined in cool scans as voxels with a standardized uptake value (SUV) of
      2.0 or greater and Hounsfield units between -250 and -10. Body composition was
      assessed by dual-energy x-ray absorptiometry. RESULTS: Although 75% of the
      subjects demonstrated visible CIBA, none had visual BAT activity after
      overfeeding. CIBA was greater than that observed in the same defined BAT voxels
      after fasting (n = 6; 2.9 +/- 0.5 vs 1.2 +/- 0.2; Delta = -1.7; 95% confidence
      interval -2.4, -1.0 SUV; P < .01). In the second cohort, CIBA was also higher
      than observed BAT voxel activity after 24 hours overfeeding (n = 8; 3.5 +/- 0.7
      vs 0.9 +/- 0.2; Delta = -2.6; 95% confidence interval -3.2, -1.9 SUV; P < .01).
      Baseline CIBA negatively correlated with changes in fat mass after 6 months (r = 
      0.72, P = .009). CONCLUSIONS: BAT may be important in weight regulation unrelated
      to the response to overeating.

PMID- 24081740
TI  - Effect of increasing glutathione with cysteine and glycine supplementation on
      mitochondrial fuel oxidation, insulin sensitivity, and body composition in older
      HIV-infected patients.
AB  - BACKGROUND: HIV-infected patients are reported to have impaired oxidation of
      fatty acids despite increased availability, suggesting a mitochondrial defect. We
      investigated whether diminished levels of a key mitochondrial antioxidant,
      glutathione (GSH), was contributing to defective fatty acid oxidation in older
      HIV-infected patients, and if so, the metabolic mechanisms contributing to GSH
      deficiency in these patients. METHODS: In an open-label design, 8 older GSH
      deficient HIV-infected males were studied before and after 14 days of oral
      supplementation with the GSH precursors cysteine and glycine. A combination of
      stable-isotope tracers, calorimetry, hyperinsulinemic-euglycemic clamp, and
      dynamometry were used to measure GSH synthesis, fasted and insulin-stimulated
      (fed) mitochondrial fuel oxidation, insulin sensitivity, body composition,
      anthropometry, forearm-muscle strength, and lipid profiles. RESULTS: Impaired
      synthesis contributed to GSH deficiency in the patients and was restored with
      cysteine plus glycine supplementation. GSH improvement was accompanied by marked
      improvements in fasted and fed mitochondrial fuel oxidation. Associated benefits
      included improvements in insulin sensitivity, body composition, anthropometry,
      muscle strength, and dyslipidemia. CONCLUSIONS: This work identifies 2 novel
      findings in older HIV-infected patients: 1) diminished synthesis due to decreased
      availability of cysteine and glycine contributes to GSH deficiency and can be
      rapidly corrected by dietary supplementation of these precursors and 2)
      correction of GSH deficiency is associated with improvement of mitochondrial fat
      and carbohydrate oxidation in both fasted and fed states and with improvements in
      insulin sensitivity, body composition, and muscle strength. The role of GSH on
      ameliorating metabolic complications in older HIV-infected patients warrants
      further investigation.

PMID- 24081741
TI  - Preoperative normalization of cortisol levels in Cushing's disease after medical
      treatment: consequences for somatostatin and dopamine receptor subtype expression
      and in vitro response to somatostatin analogs and dopamine agonists.
AB  - CONTEXT: Corticotroph pituitary adenomas often highly express the dopamine 2
      receptor (D2R) and somatostatin receptor subtype 5 (sst5). The sst2 expression is
      relatively low, likely resulting from downregulating effects of high cortisol
      levels. This may explain why the sst2-preferring somatostatin analog octreotide,
      compared with the multi-receptor-targeting somatostatin analog pasireotide, is
      generally ineffective in Cushing's disease. OBJECTIVE: Our objective was to
      compare sst and D2R expression levels between adenomas from patients with
      elevated and normalized preoperative urinary free cortisol excretion. PATIENTS
      AND DESIGN: Corticotroph adenoma tissue was examined from patients from group 1
      (n = 22; elevated preoperative urinary free cortisol) and group 2 (n = 11; mean
      duration of preoperative normocortisolism 10 weeks). Somatotroph adenoma tissue
      from 10 acromegalic patients was examined to compare receptor expression
      profiles. MAIN OUTCOME MEASURES: We evaluated receptor mRNA and protein
      expression levels and effects of octreotide, pasireotide, and cabergoline on ACTH
      secretion by cultured human corticotroph adenoma cells. RESULTS: The sst2 mRNA
      expression in group 2 was 10-fold higher than in group 1 (P < .01), even
      comparable to that in somatotroph adenomas. There were no statistically
      significant differences in sst5 and D2R mRNA expression or in sst2, sst5, and D2R
      protein expression between both groups of corticotroph adenomas. In responders,
      octreotide (n = 2 out of 4; -30.5% +/- 10.4%) was less potent than pasireotide (n
      = 5 out of 6; -47.0% +/- 4.2%) and cabergoline (n = 3 out of 4; -41.9% +/- 3.1%)
      with respect to inhibition of ACTH secretion by adenomas from group 2.
      CONCLUSIONS: After achieving normocortisolism induced by medical therapy,
      cortisol-mediated sst2 downregulation on corticotroph adenomas appears to be a
      reversible process at the mRNA but not at the protein level. Octreotide remains
      less potent than pasireotide and cabergoline with respect to in vitro inhibition
      of ACTH secretion. Whether sustained normocortisolism induced by medical therapy
      induces re-expression of functional sst2 protein in corticotroph adenomas and
      whether this increases the ACTH-lowering potency of octreotide remains to be
      established.

PMID- 24081742
TI  - The impact of depot GnRH agonist on AMH levels in healthy reproductive-aged
      women.
AB  - CONTEXT: GnRH agonists (GnRHa) are being used experimentally in an attempt to
      preserve fertility in young female cancer patients undergoing chemotherapy. Anti
      Mullerian hormone (AMH) produced by ovarian granulosa cells may serve as a marker
      of ovarian reserve, but it is not clear whether this marker is useful during
      GnRHa treatment. OBJECTIVE: The purpose of this study was to determine the effect
      of a depot GnRHa on AMH levels. DESIGN: Depot leuprolide (3.75 mg) was
      administered in the midluteal phase (MLP) in healthy women. Assessments of AMH,
      FSH, LH, estradiol, and progesterone were performed in the early follicular phase
      (EFP) and MLP before GnRHa treatment and approximately 7, 14, and 30 days after
      GnRHa administration. SETTING: The study was conducted in a university research
      center. PATIENTS: Participants were 33 healthy, premenopausal women aged 18 to 45
      years old with regular menses. RESULTS: EFP and MLP AMH levels were similar
      before GnRHa administration. Relative to MLP AMH levels, AMH decreased 7 days
      after GnRHa administration by a median of 24% (P < .001) and then increased above
      pretreatment levels 14 and 30 days after GnRHa by 13% and 32%, respectively (P <
      .001). Changes in AMH levels did not correlate with changes in gonadotropins,
      estradiol, or progesterone. CONCLUSIONS: Significant changes in AMH levels occur
      in the first 4 weeks after depot leuprolide administration, suggesting that AMH
      may not be a reliable marker of ovarian reserve during this interval. Changes in
      AMH occurred independent of gonadotropin levels, supporting a direct effect of
      GnRHa on granulosa cell expression of AMH or an indirect effect of GnRHa on the
      development and/or dynamics of the follicle pool.

PMID- 24081743
TI  - Application of a benthic observed/expected-type model for assessing Central
      Appalachian streams influenced by regional stressors in West Virginia and
      Kentucky.
AB  - Stream bioassessments rely on taxonomic composition at sites compared with
      natural, reference conditions. We developed and tested an observed/expected (O/E)
      predictive model of taxonomic completeness and an index of compositional
      dissimilarity (BC index) for Central Appalachian streams using combined
      macroinvertebrate datasets from riffle habitats in West Virginia (WV) and
      Kentucky (KY). A total of 102 reference sites were used to calibrate the O/E
      model, which was then applied to assess over 1,200 sites sampled over a 10-year
      period. Using an all subsets discriminant function analysis (DFA) procedure, we
      tested combinations of 14 predictor variables that produced DF and O/E models of
      varying performance. We selected the most precise model using a probability of
      capture at >0.5 (O/E0.5, SD = 0.159); this model was constructed with only three
      simple predictor variables--Julian day, latitude, and whether a site was in
      ecoregion 69a. We evaluated O/E and BC indices between reference and test sites
      and compared their response to regional stressors, including coal mining,
      residential development, and acid deposition. The Central Appalachian O/E and BC
      indices both showed excellent discriminatory power and were significantly
      correlated to a variety of regional stressors; in some instances, the BC index
      was slightly more sensitive and responsive than the O/E0.5 model. These indices
      can be used to supplement existing bioassessment tools crucial to detecting and
      diagnosing stream impacts in the Central Appalachian region of WV and KY.

PMID- 24081744
TI  - Pyrimethanil residue and dissipation in tomatoes and soil under field conditions.
AB  - A residue analytical method to detect pyrimethanil in tomatoes and soil was
      developed by using high-performance liquid chromatography with a diode array
      detector. The dissipation and residue level of pyrimethanil in tomatoes and soil
      were also investigated. Results showed that the average recoveries are in the
      range of 87.2 to 90.0 % with a relative standard difference of 2.22 to 7.61 % in
      tomatoes and soil. In Guangdong, Shandong, and Yunnan, the half-lives of
      pyrimethanil in tomatoes were 1.8, 3.6, and 4.2 days and those in soil were 4.0,
      3.3, and 3.9 days, respectively. The dissipation rate of pyrimethanil in tomatoes
      and soil was affected by temperature, precipitation, and soil type. The terminal
      residue results showed that when pesticide pyrimethanil was used under the
      experiment design, all the results were far below the available maximum residue
      limits. Low residues in tomatoes and soil suggest that this pesticide is safe to
      use under the recommended dosage. 

PMID- 24081745
TI  - Response to: Comment on 'Effect of a low dose of gonadotropin releasing hormone
      antagonist on in vitro fertilization outcomes' by Kerimoglu et al.: Cetrorelix in
      COH cycles: time to re-evaluate the daily administered dose?

PMID- 24081746
TI  - Cetrorelix in COH cycles: time of change for the daily administered dose? A
      response to Kerimoglu et al. (10.1007/s00404-013-2806-z).

PMID- 24081747
TI  - Medicinal leech therapy in pain syndromes: a narrative review.
AB  - Medicinal leech therapy is used in a variety of conditions; most of which have
      pain as a major symptom. Its mode of action relies on the injection of leech
      saliva into patients' tissues during the process of blood withdrawal. Leech
      saliva contains active ingredients with anti-inflammatory, thrombolytic, anti
      coagulant and blood- and lymph-circulation enhancing properties. A specific
      analgesic substance within the leech saliva is yet to be identified. Pain relief
      from leech therapy is rapid, effective and long-lasting in many conditions. This
      review compiles studies and case reports that provide clinical evidence for leech
      therapy's analgesic effects.

PMID- 24081748
TI  - [Osteoporosis: therapy in interface management].
AB  - Osteoporosis is defined as a systemic bone disorder with decreased bone strength
      and an increased susceptibility for fragility fractures. In particular elderly
      people face an increased fracture risk. Fracture stabilisation by different
      methods of osteosynthesis and fast remobilisation has become standard procedures
      after a fragility fracture due to osteoporosis. However, only a small group of
      patients receive osteoporosis drug therapy with the aim to reduce the rate of
      further fractures. In literature this has been described as "osteoporosis care
      gap". In the past, various projects have been performed in order to overcome this
      problem of osteoporosis care after fragility fractures. The article presents the
      current problems in daily routine concerning the initiation of an osteoporosis
      therapy after a fracture. A simple concept of necessary procedures and questions
      is presented as a possible solution for the interface management of osteoporosis
      drug therapy after fragility fractures. In addition, current osteoporosis
      therapies are presented in the view of care for geriatric patients. 

PMID- 24081750
TI  - Boundary cartilage lubrication: review of current concepts.
AB  - Effective lubrication of synovial joints is important to prevent cartilage
      degeneration and to keep the joints healthy. This paper sets out the basics of
      engineering lubrication with respect to the composition and properties of
      synovial fluid constituents. Two basic types of boundary lubrication are
      discussed: the presence of highly hydrophilic proteoglycans that provide a water
      liquid film, and the existence of multilamellar phospholipids lubricating layers
      at the surface ofarticular cartilage. Based on current knowledge, we may conclude
      that no single mechanism of boundary lubrication exists, and that effective
      boundary lubrication of synovial joints is maintained by the synergic effect of
      all synovial fluid constituents.

PMID- 24081751
TI  - Future directions for the ERS: presidential plans.

PMID- 24081749
TI  - [Current diagnostic requirements in chronic myeloid leukemia].
AB  - In patients with chronic myeloid leukemia, high-quality diagnostics is of
      paramount importance for the surveillance of treatment efficacy. The availability
      of new tyrosine kinase inhibitors providing more rapid and deeper responses
      requires the employment of standardized and highly sensitive diagnostic methods
      to ensure optimal monitoring of the patients. This review presents the current
      international diagnostic standards and the certified laboratories in Austria. 

PMID- 24081752
TI  - Reaching the golden milestone. The 2013 ERS Dublin summit: preparing the road to
      Rome.

PMID- 24081753
TI  - The MABA approach: a new option to improve bronchodilator therapy.

PMID- 24081754
TI  - Does left heart disease cause most systemic sclerosis associated pulmonary
      hypertension?

PMID- 24081755
TI  - Why inflammatory phenotyping is necessary for successful drug evaluation in
      asthma and COPD.

PMID- 24081756
TI  - Sildenafil: a definitive NO in COPD.

PMID- 24081757
TI  - Biomarker-guided clinical decisions: for patients, health economists or neither?

PMID- 24081758
TI  - From pollen count to pollen potency: the molecular era of aerobiology.

PMID- 24081759
TI  - Adopting universal lung function reference equations.

PMID- 24081761
TI  - An official American Thoracic Society and European Respiratory Society policy
      statement: disparities in respiratory health.
AB  - Health disparities, defined as a significant difference in health between
      populations, are more common for diseases of the respiratory system than for
      those of other organ systems, because of the environmental influence on breathing
      and the variation of the environment among different segments of the population.
      The lowest social groups are up to 14 times more likely to have respiratory
      diseases than are the highest. Tobacco smoke, air pollution, environmental
      exposures, and occupational hazards affect the lungs more than other organs and
      occur disproportionately in ethnic minorities and those with lower socioeconomic
      status. Lack of access to quality healthcare contributes to disparities. The
      executive committees of the American Thoracic Society (ATS) and European
      Respiratory Society (ERS) established a writing committee to develop a policy on
      health disparities. The document was reviewed, edited, and approved by their full
      executive committees and boards of directors of the societies. This document
      expresses a policy to address health disparities by promoting scientific inquiry
      and training, disseminating medical information and best practices, and
      monitoring and advocating for public respiratory health. The ERS and the ATS have
      strong international commitments and work with leaders from governments,
      academia, and other organisational bodies to address and reduce avoidable health
      inequalities. Their training initiatives improve the function of healthcare
      systems and health equality. Both the ATS and the ERS support all aspects of this
      document, confer regularly, and act together when possible, but the activities to
      bring about change may vary because of the differences in the continents where
      the two organisations carry out most of their activities. The ATS and ERS pledge
      to frame their actions to reduce respiratory health disparities. The vision of
      the ATS and ERS is that all persons attain better and sustained respiratory
      health. They call on all their members and other societies to join in this
      commitment. 

PMID- 24081762
TI  - Case series reporting the effectiveness of mycophenolate mofetil in treatment
      resistant asthma.

PMID- 24081763
TI  - Arterial stiffness by pulse wave velocity in COPD: reliability and
      reproducibility.

PMID- 24081764
TI  - No TWEAK for COPD.

PMID- 24081765
TI  - Genome-wide genetic ancestry measurements to predict lung function in European
      populations.

PMID- 24081766
TI  - Amikacin treatment for multidrug resistant tuberculosis: how much monitoring is
      required?

PMID- 24081767
TI  - An integrated model involving sleep units and primary care for the diagnosis of
      sleep apnoea.

PMID- 24081768
TI  - Trying to find a cure for cystic fibrosis: CFTR biomarkers as outcomes.

PMID- 24081769
TI  - Trying to find a cure for cystic fibrosis: CFTR biomarkers as outcomes.

PMID- 24081770
TI  - Allergic burden and the risk of venous thromboembolism.

PMID- 24081771
TI  - Allergic burden and the risk of venous thromboembolism.

PMID- 24081772
TI  - Is the sensitivity of primary ciliary dyskinesia detection by ciliary function
      analysis 100%?

PMID- 24081773
TI  - Is the sensitivity of primary ciliary dyskinesia detection by ciliary function
      analysis 100%?

PMID- 24081777
TI  - Noninvasive fractional flow reserve derived from computed tomography angiography
      for coronary lesions of intermediate stenosis severity: results from the DeFACTO
      study.
AB  - BACKGROUND: Fractional flow reserve derived from computed tomography angiography
      (FFRCT) is a noninvasive method for diagnosis of ischemic coronary lesions. To
      date, the diagnostic performance of FFRCT for lesions of intermediate stenosis
      severity remains unexamined. METHODS AND RESULTS: Among 407 vessels from 252
      patients at 17 centers who underwent CT, FFRCT, invasive coronary angiography,
      and invasive FFR, we identified 150 vessels of intermediate stenosis by CT,
      defined as 30% to 69% stenosis. FFRCT, FFR, and CT were interpreted in blinded
      fashion by independent core laboratories. FFRCT and FFR <=0.80 were considered
      hemodynamically significant, whereas CT stenosis >=50% was considered
      obstructive. Diagnostic performance of FFRCT versus CT was assessed for accuracy,
      sensitivity, specificity, positive predictive values, and negative predictive
      values. Area under the receiver operating characteristic curve and net
      reclassification improvement were evaluated. For lesions of intermediate stenosis
      severity, accuracy, sensitivity, specificity, positive predictive value, and
      negative predictive value of FFRCT were 71%, 74%, 67%, 41%, and 90%, whereas
      accuracy, sensitivity, specificity, positive predictive value, and negative
      predictive value of CT stenosis were 63%, 34%, 72%, 27%, and 78%. FFRCT
      demonstrated superior discrimination compared with CT stenosis on per-patient
      (area under the receiver operating characteristic curve, 0.81 versus 0.50;
      P=0.0001) and per-vessel basis (area under the receiver operating characteristic
      curve, 0.79 versus 0.53; P<0.0001). FFRCT demonstrated significant
      reclassification of CT stenosis for lesion-specific ischemia (net
      reclassification improvement, 0.45; 95% confidence interval, 0.25-0.65; P=0.01).
      CONCLUSIONS: FFRCT possesses high diagnostic performance for diagnosis of
      ischemic for lesions of intermediate stenosis severity. Notably, the high
      sensitivity and negative predictive value suggest the ability of FFRCT to
      effectively rule out intermediate lesions that cause ischemia.

PMID- 24081778
TI  - The effect of manganese-induced cytotoxicity on mRNA expressions of HSP27, HSP40,
      HSP60, HSP70 and HSP90 in chicken spleen lymphocytes in vitro.
AB  - The purpose of this study was to investigate the effect of manganese (Mn)-induced
      cytotoxicity on heat shock proteins in chicken spleen lymphocytes. Lymphocytes
      were cultured in medium in the absence and presence of MnCl2 (2 * 10(-4), 4 * 10(
      4), 6 * 10(-4), 8 * 10(-4), 10 * 10(-4), and 12 * 10(-4) mmol/L) for 12, 24, 36,
      and 48 h in vitro. Then, the mRNA levels of HSP27, HSP40, HSP60, HSP70, and HSP90
      were examined by real-time quantitative PCR. The results showed that the mRNA
      levels of HSP27, HSP40, HSP60, HSP70, and HSP90 in all treatment groups at all
      time points, except mRNA levels of HSP27 at 48 h, had the same tendency. As
      manganese concentration increased, the mRNA expression of the heat shock proteins
      first increased and then decreased. In other words, we demonstrated that the mRNA
      expression of the heat shock proteins was induced at lower concentrations of
      manganese and was inhibited at higher concentrations. Mn had a dosage-dependent
      effect on HSP27, HSP40, HSP60, HSP70, and HSP90 mRNA expression in chicken spleen
      lymphocytes in vitro.

PMID- 24081779
TI  - Effect of lower doses of vanadate in combination with Azadirachta indica leaf
      extract on hepatic and renal antioxidant enzymes in streptozotocin-induced
      diabetic rats.
AB  - The present study was undertaken to investigate short-term (21 days) effects of
      oral administration of Azadirachta indica leaf extract and vanadate, separately
      and in combination, on the activities of antioxidant enzymes in streptozotocin
      induced diabetic rats. Vanadate is a remarkable antidiabetic agent and shows
      insulin mimetic effect. However, severe toxicity is associated with vanadate when
      used in high concentration while at lower concentration the hypoglycemic property
      of vanadate is reduced. So, we used a low dose of vanadate in combination with A.
      indica leaf extract and evaluated their effect on the antioxidant defense system.
      Streptozotocin-diabetic rats were treated separately with insulin, vanadate (0.6
      mg/ml), A. indica, and with combined dose of vanadate (0.2 mg/ml) and A. indica.
      At the end of the experiment, rats were sacrificed and serum glucose levels and
      activities of superoxide dismutase, catalase, glutathione peroxidase, and
      glutathione reductase were determined in cytosolic fraction of liver and kidney.
      Diabetic rats showed hyperglycemic condition and alteration in antioxidant enzyme
      activities. Treatment with antidiabetic compounds resulted in the reduction of
      glucose levels and restoration of enzyme activities to normal. Results showed
      that combined treatment of vanadate and A. indica leaf extract was the most
      effective in normalizing altered antioxidant enzyme system.

PMID- 24081780
TI  - Selenium deficiency is associated with endoplasmic reticulum stress in a rat
      model of cardiac malfunction.
AB  - The relationship between selenium (Se) deficiency-induced cardiac malfunction and
      endoplasmic reticulum (ER) stress is poorly understood. In the present study, 18
      weaning Sprague Dawley rats were randomly fed with three different Se diets, and
      myocardial glutathione peroxidase (GPx) activity was measured by an enzyme
      activity assay. Cardiac function was evaluated by hemodynamic parameters. ER
      stress markers immunoglobulin-binding protein (BiP)/glucose-regulated protein 78
      (GRP78) and C/EBP homologous protein (CHOP) were detected by western blotting.
      Our data showed that myocardial GPx activity and cardiac function were
      conspicuously impaired in Se-deficient rats. Expression of GRP78 and CHOP was
      significantly upregulated by treatment of Se deficiency. Improvements in
      myocardial GPx activity and cardiac function, as well as decreases in expression
      of GRP78 and CHOP, were observed after Se supplementation. Consequently, our data
      show that ER stress was involved in Se deficiency-induced cardiac dysfunction. 

PMID- 24081782
TI  - [The bezoar in the biliodigestive loop as a rare complication after BII operation
      in the absence of Brown-Fubetapunktanastomose].

PMID- 24081783
TI  - [Ganglioglioma along the visual pathway -- a rare location].

PMID- 24081784
TI  - Cardiac MRI: T2-Mapping Versus T2-Weighted Dark-Blood TSE Imaging for Myocardial
      Edema Visualization in Acute Myocardial Infarction.
AB  - PURPOSE: To assess the diagnostic accuracy of T2 mapping for the detection of
      myocardial edema in acute myocardial infarction (AMI), and to compare this
      diagnostic accuracy with that of the current standard for myocardial edema
      imaging, which is T2w dark-blood TSE imaging. MATERIALS AND METHODS: 29 patients
      with AMI were examined at 1.5 T. For the visualization of myocardial edema, T2
      maps, calculated from three T2w SSFP images, and T2w dark-blood TSE images were
      acquired in standard short- and long-axis views. Cine SSFP images were acquired
      for the analysis of left ventricular (LV) function and late gadolinium
      enhancement images (LGE) for the visualization of myocardial necrosis. The T2
      maps as well as the T2w dark-blood TSE images were evaluated twice independently
      from the cine SSFP and LGE images. The presence or absence of myocardial edema
      was rated visually for each LV segment. As the standard of reference, the infarct
      zone was defined based on the cine SSFP and the LGE images. RESULTS: In this
      segment-based analysis, T2 mapping showed a sensitivity of 82 % and a specificity
      of 94 % for the detection of edema in the infarct zone. T2w dark-blood TSE
      imaging revealed a sensitivity of 50 % and a specificity of 98 %. T2 mapping
      showed a higher intra-rater agreement compared to T2w dark-blood TSE imaging
      (kappa: 0.87 vs. 0.76). CONCLUSIONS: T2 mapping allows for the visualization of
      myocardial edema in AMI with a high sensitivity and specificity, and features
      better diagnostic accuracy in terms of a higher sensitivity compared to T2w dark
      blood TSE imaging. Citation Format: * Nabetaenstein K, Nensa F, Schlosser T et
      al. Cardiac MRI: T2-Mapping Versus T2-Weighted Dark-Blood TSE Imaging for
      Myocardial Edema Visualization in Acute Myocardial Infarction. Fortschr
      Rontgenstr 2014; 186: 166 - 172.

PMID- 24081781
TI  - Epigenetics of neural repair following spinal cord injury.
AB  - Spinal cord injury results from an insult inflicted on the spinal cord that
      usually encompasses its 4 major functions (motor, sensory, autonomic, and
      reflex). The type of deficits resulting from spinal cord injury arise from
      primary insult, but their long-term severity is due to a multitude of
      pathophysiological processes during the secondary phase of injury. The failure of
      the mammalian spinal cord to regenerate and repair is often attributed to the
      very feature that makes the central nervous system special-it becomes so highly
      specialized to perform higher functions that it cannot effectively reactivate
      developmental programs to re-build novel circuitry to restore function after
      injury. Added to this is an extensive gliotic and immune response that is
      essential for clearance of cellular debris, but also lays down many obstacles
      that are detrimental to regeneration. Here, we discuss how the mature chromatin
      state of different central nervous system cells (neural, glial, and immune) may
      contribute to secondary pathophysiology, and how restoring silenced developmental
      gene expression by altering histone acetylation could stall secondary damage and
      contribute to novel approaches to stimulate endogenous repair. 

PMID- 24081785
TI  - Radiologic resectability assessment in pancreatic cancer.
AB  - Complete tumor resection is still the only potentially curative therapy option
      for patients with ductal adenocarcinoma of the pancreas. Surgical exploration is
      the gold standard for the determination of tumor resectability. Radiological
      resectability assessment is of great importance because many clearly unresectable
      cases can be identified preoperatively and it became essential for surgical
      planning. The evolving surgical and radiological techniques demand a continuous
      reappraisal of radiological criteria in resectability assessment. In the
      following, the criteria for resection planning are described along with surgical
      management and the role of radiology in some innovative surgical concepts is
      explained.

PMID- 24081786
TI  - Various techniques of stent-assisted coil embolization of wide-necked or fusiform
      artherosclerotic and dissecting unruptured vertebrobasilar artery aneurysms for
      reducing recanalization: mid-term results.
AB  - BACKGROUND: Coil embolization of wide-necked or fusiform vertebrobasilar
      aneurysms is challenging and tends to involve frequent recanalization. PURPOSE:
      The aim of our study was to evaluate complications and mid-term outcomes of
      complex vertebrobasilar artery aneurysms after stent-assisted coiling with
      various techniques. METHODS: We retrospectively evaluated 28 cases of unruptured
      vertebrobasilar aneurysm treated by stent-assisted coiling. RESULTS: Forty-four
      of the 45 stents placed in 28 patients were deployed at the desired location
      (97.8 %). Single stent-assisted coiling was performed in 14 aneurysms, a stent
      within-a-stent (SWS) technique was used in 12 aneurysms, and Y-stent-assisted
      coiling was employed in four basilar tip aneurysms. Two basilar tip aneurysms
      treated by single stent-assisted coiling recurred and were retreated by SWS and Y
      stent-assisted coiling. Complete embolization was achieved in 19 aneurysms (67.8
      %), and remnant neck persisted in eight aneurysms (28.6 %) and remnant aneurysm
      was noted in one aneurysm (3.6 %). Permanent neurologic deficit (Modified Rankin
      Scale 1 and 4) was noted in two patients (7.1 %). Angiographic follow-up (mean
      follow-up period: 20.8 months) was performed in 20 patients. Major recanalization
      occurred in two basilar tip aneurysms (10 %) and minor compaction was noted in
      one superior cerebellar artery aneurysm. The remaining 17 aneurysms were stable
      or improved (85 %). CONCLUSIONS: Complex vertebrobasilar aneurysm embolization
      with stent-assisted techniques was effective and feasible as a method for
      reducing recanalization during midterm angiographic follow-up. Large and wide
      necked basilar tip aneurysms showed frequent major recanalization, and compact
      packing with single or Y-stent-assisted coiling is needed to prevent
      recanalization even if coiling will be done without stenting.

PMID- 24081787
TI  - Plurihormonal pituitary adenoma with concomitant adrenocorticotropic hormone
      (ACTH) and growth hormone (GH) secretion: a report of two cases and review of the
      literature.
AB  - Plurihormonal pituitary adenomas are tumours that show immunoreactivity for more
      than one hormone that cannot be explained by normal adenohypophysial
      cytodifferentiation. The most common combinations in these adenomas include
      growth hormone (GH), prolactin (PRL) and one or more glycoprotein hormone sub
      units (beta-TSH, beta-FSH, beta-LH and alphaSU). The authors report two cases of
      a plurihormonal pituitary adenoma expressing the rare combination of ACTH and GH.
      They both underwent successful transphenoidal hypophysectomy (TSH). Long-term
      post-operative follow-up revealed no evidence of tumour recurrence. Due to the
      multiple secretions and plurihormonal characteristics clinical diagnosis of
      composite pituitary adenomas can be difficult. The authors discuss the diagnosis
      and management of composite pituitary adenomas and review the literature
      regarding this rare phenomenon. 

PMID- 24081788
TI  - Fluorescein sodium in brain tumor surgery - Response.

PMID- 24081789
TI  - Pneumocystis pneumonia in patients treated with long-term steroid therapy for
      symptom palliation: a neglected infection in palliative care.
AB  - We report 3 cases of pneumocystis pneumonia (PCP) in patients with advanced
      cancer who received palliative care. All patients received long-term steroid
      therapy for symptom management. A diagnosis of PCP was based on clinical symptoms
      and a positive Pneumocystis jiroveci polymerase chain reaction test from induced
      sputum specimens. Despite appropriate treatment, only 1 patient recovered from
      PCP. Long-term steroid, often prescribed in palliative care settings, is the most
      common risk factor for PCP in non-HIV patients. Pneumocystis pneumonia may cause
      distressing symptoms such as severe dyspnea, and the mortality rate is high.
      Therefore, it is important to consider PCP prophylaxis for high-risk patients and
      to diagnose PCP early and provide appropriate treatment to alleviate PCP-related
      symptoms and avert unnecessary shortening of a patient's life expectancy. 

PMID- 24081790
TI  - High-dose neuroleptics and neuroleptic rotation for agitated delirium near the
      end of life.
AB  - REASON FOR THE STUDY: Agitated delirium presents unique challenges for hospice
      and palliative care clinicians. Haloperidol, the recommended neuroleptic, may be
      ineffective at low dose, or poorly tolerated at higher doses. MAIN FINDINGS: This
      article reports on two patients with refractory agitated delirium. Both developed
      extrapyramidal symptoms from haloperidol and required rotation to an alternate
      neuroleptic. Patient #1 received 2000 mg/day oral chlorpromazine. Patient #2
      received greater than 200 mg/day sublingual olanzapine. Control of agitation was
      achieved, though the doses were substantially higher than has previously reported
      in the literature. Each patient experienced considerable sedation, though this
      was an acceptable side effect for the family. Each patient was transferred from
      the acute care hospital to a location of family preference. There they died
      within a week of transfer. CONCLUSIONS: Agitated delirium is a palliative care
      emergency. High doses of neuroleptic medications, with rotation to an alternate
      neuroleptic when side effects occur with standard haloperidol, may effectively
      palliate agitated delirium. This remedy can provide the patient with a peaceful
      dying in a place of their choosing.

PMID- 24081791
TI  - Endoscope-assisted concurrent resection of thyroglossal duct cysts and benign
      thyroid nodules via a small submental incisions.
AB  - The objective of this study was to evaluate the technique of endoscope-assisted
      concurrent resection of thyroglossal duct cysts and benign thyroid nodules via a
      small submental incision. Endoscope-assisted thyroglossal duct cyst excision and
      subtotal thyroidectomy were performed via a small submental incision in six
      patients with thyroglossal duct cysts and benign nodular thyroid lesions. The
      thyroglossal duct cysts and thyroid lesions were completely excised. The
      incisions were 3-4 cm in length, and the mean operation time was 84 +/- 11 min.
      The mean volume of blood loss was 19 +/- 5 mL. Postoperative pathological
      examination findings confirmed the diagnosis of thyroglossal duct cyst in all
      patients. The thyroid lesions were nodular goiter in three patients and thyroid
      adenoma in three patients. No postoperative complications such as hematoma,
      pharyngeal fistula, hypocalcemia, recurrent laryngeal nerve paralysis, or
      dysphagia were observed. No changes in the planned surgical procedure were
      required, and no recurrent lesions were detected during follow-up. In conclusion,
      patients with thyroglossal duct cysts and benign thyroid lesions can be treated
      by endoscopic excision via a small submental incision, thereby avoiding large
      neck incisions and resulting in better postoperative cosmetic outcomes. 

PMID- 24081792
TI  - Accuracy of high-resolution computed tomography in locating facial nerve injury
      sites in temporal bone trauma.
AB  - In this study, high-resolution, multislice computed tomography findings are
      compared with surgical findings in terms of the fracture location in patients
      with traumatic facial paralysis. Patients with traumatic facial paralysis with
      grade VI House-Brackmann scale who met the criteria for surgical decompression
      between 2008 and 2012 were included in this study. All the patients underwent a
      multislice high-resolution, multislice computed tomography (HRCT) using 1-mm
      thick slices with a bone window algorithm. The anatomical areas of the temporal
      bone (including the Fallopian canal) were assessed by CT and during the surgery
      (separately by the radiologist and the surgeon), and fracture line involvement
      was recorded. Forty-one patients entered this study. The perigeniculate area was
      the most commonly involved region (46.34 %) of the facial nerve. The sensitivity
      and specificity of HRCT to detect a fracture line seems to be different in
      various sites, but the overall sensitivity and specificity were 77.5 and 77.7 %,
      respectively. Although HRCT is the modality of choice in traumatic facial
      paralysis, the diagnostic value may differ according to the fracture location.
      The results of HRCT should be considered with caution in certain areas.

PMID- 24081795
TI  - Ovarian cancer: a brief historical overview of intraperitoneal trials.
AB  - The standard platinum-based treatment of previously untreated advanced ovarian
      cancer continues to evolve because despite high response rates to such first-line
      treatment, a majority of patients will experience relapse. For many years, the
      optimal treatment for women with advanced ovarian cancer has been maximum
      cytoreductive surgery followed by intravenous (IV) platinum and taxane
      chemotherapy. Later, several randomized multicenter phase III clinical trials
      demonstrated that intraperitoneal (IP) chemotherapy was superior to standard IV
      chemotherapy when there was minimal residual disease after primary debulking
      surgery. The underlying rationale for use of IP therapy is based on the dose
      effect relationship for platinum drugs in ovarian cancer. However, barriers to
      implementation of IP therapy in the routine clinical setting include concern for
      toxicity, tolerability of planned treatment, and catheter-related complications.
      In this article, we highlight the key trials and recent directions in IP therapy
      of ovarian cancer and briefly discuss another approach to the delivery of IP
      chemotherapy, known as hyperthermic intraperitoneal chemotherapy. 

PMID- 24081796
TI  - Local recurrence patterns in breast cancer patients treated with oncoplastic
      reduction mammaplasty and radiotherapy.
AB  - BACKGROUND: The purpose of this study was to describe the incidence and location
      of ipsilateral breast tumor recurrence (IBTR) among breast cancer patients
      treated with oncoplastic reduction mammoplasty (ORM) and radiotherapy (RT).
      METHODS: The medical records of 86 consecutive women with ductal carcinoma in
      situ (DCIS) (n = 11) or invasive carcinoma of the breast (n = 75) treated with
      ORM at Emory University between January 1994 and December 2010 were reviewed.
      RESULTS: Following ORM, prolonged wound healing or surgical complications led to
      delay of adjuvant chemotherapy or RT in 11 patients. Surgical clips were found
      outside the primary tumor breast quadrant in 43 % of the patients with available
      RT planning CT images. When the clips were found outside the primary tumor
      quadrant, the RT boost was more frequently delivered outside versus inside the
      primary tumor quadrant (67 vs. 33 %, p < 0.001). After a median follow-up period
      of 4.5 years (range 0.1-17.9), 6 patients developed an IBTR and only 1 IBTR
      occurred outside the primary tumor quadrant. The 5-year ipsilateral breast tumor
      control rates were 91 % (95 % CI 0.82-0.99) and 93 % (95 % CI 0.90-0.97) for
      patients with DCIS and invasive carcinoma, respectively. CONCLUSIONS: The use of
      ORM yields acceptable rates of IBTR. ORM may displace breast tissue and surgical
      clips to breast quadrants outside of the original tumor location, but the
      majority of IBTRs still occur in the original tumor quadrant. This area remains
      at highest risk of in-breast recurrence in women treated with ORM irrespective of
      surgical clip location.

PMID- 24081797
TI  - Ovarian cancer in BRCA mutation carriers: improved outcome after intraperitoneal
      (IP) cisplatin.
AB  - BACKGROUND: Ovarian cancer arising in women with BRCA mutations is known to have
      a more favorable outcome and to be more responsive to platinum-based regimens
      than in those without a hereditary background. We analyze our previously
      published intraperitoneal (IP) studies in relation to BRCA mutation status and
      update their outcomes. METHODS: Among 62 patients with ovarian cancer enrolled in
      IP platinum doublet studies in clinical trials (with etoposide (n = 18), with
      floxuridine (n = 30), and with topotecan (n = 14)), a deleterious BRCA mutation
      was eventually identified in 10 patients. The outcomes in these BRCA mutation
      carriers are described and compared with survival of others in respective trials.
      RESULTS: Ten patients that were confirmed to have BRCA mutations-all with high
      grade and stages IIC to IV disease-survived a median of 10 years (range: 4-18+)
      after receiving IP cisplatin-based regimens. Two continue with no evidence of
      disease since their IP treatment, while four others remain alive with recurrences
      after 8, 9, 10, and 11 years, respectively. CONCLUSIONS: This experience suggests
      that IP cisplatin leads to favorable long term outcomes in advanced ovarian
      cancer in women with defective homologous recombination (i.e., with deleterious
      BRCA mutations). Whether such cisplatin dose-intensification from IP relative to
      (intravenous) IV drug administration leads to superior results in these mutation
      carriers requires further study.

PMID- 24081798
TI  - The effect of elevated body mass index on outcomes following cytoreductive
      surgery with hyperthermic intraperitoneal chemotherapy.
AB  - BACKGROUND: Cytoreductive surgery with hyperthermic intraperitoneal chemotherapy
      (CRS-HIPEC) can prolong survival in peritoneal-based malignancies. These
      malignancies harbor in visceral and omental adipose tissue, and as a result,
      obesity may contribute to greater tumor burden. Obesity also is an independent
      risk factor for perioperative complications following major surgery. No studies
      to date have investigated the effect of elevated body mass index (BMI) on disease
      burden and perioperative outcomes in CRS-HIPEC patients. METHODS: Observational
      study of consecutive patients taken to the operating suite from 2007 to 2012 for
      CRS-HIPEC. Data were reviewed retrospectively, and patients for whom complete
      cytoreduction was not achieved and those with BMI <18.5 were excluded. Various
      operative data points, including peritoneal cancer index, surgery length, and
      estimated blood loss, were measured prospectively. Perioperative complications
      were identified and recorded. RESULTS: Complete data for review was available for
      114 patients. Patients were subdivided based on BMI (group A 18.5-24.9, n = 43;
      group B 25-29.9, n = 49; group C >= 30, n = 22). There was no statistically
      significant difference in tumor burden, operative length, probability of
      unresectable disease, operative blood loss, or length of stay between groups.
      Rates of respiratory, gastrointestinal, infectious, renal, and hematologic
      complications were not statistically different, with the exception of deep vein
      thrombosis (A = 0, B = 13.5 %, C = 0; p = 0.026). CONCLUSIONS: CRS-HIPEC can be
      safely performed in overweight and obese patients without significant increase in
      perioperative morbidity. Despite the limitations in physical examination and
      increase in visceral fat, they do not appear to present later than patients with
      normal BMI, nor do they have higher tumor burden.

PMID- 24081799
TI  - Cytoreductive surgery in advanced GIST: timing is everything.

PMID- 24081800
TI  - The role of thyroidectomy in metastatic disease to the thyroid gland.
AB  - BACKGROUND: Whether thyroidectomy for metastases to the thyroid is associated
      with a survival benefit remains debatable; in general, palliation and disease
      control are accepted goals in this setting. We evaluated the clinical features
      and overall survival of patients with thyroid metastasis treated by thyroid
      resection or nonoperatively. METHODS: This retrospective analysis included 90
      patients identified with metastasis to the thyroid confirmed pathologically via
      thyroidectomy (n = 31) or fine-needle aspiration biopsy (n = 59). Overall
      survival was calculated by the Kaplan-Meier method, and differences between
      groups were calculated by Pearson's chi (2) coefficient. RESULTS: The most common
      primary malignancies were renal cell (20%), head and neck (19%), and lung (18%).
      The median time from primary tumor diagnosis to thyroid metastasis diagnosis was
      37.4 months (range 0-210 months). Most metastases (69%) were metachronous, and
      12% were isolated. The median follow-up after diagnosis of thyroid metastasis was
      11.5 months (range 0-112 months). Median overall survival was longer in
      thyroidectomy patients compared to the fine-needle aspiration group (34 vs. 11
      months, P < 0.0001). Patients with renal cell primary tumors were more likely to
      undergo thyroidectomy than patients with other primary tumors (78 vs. 24%, P <
      0.0001). Nearly all patients with lung primary tumors died within 24 months of
      thyroid metastasis diagnosis, and thyroidectomy was only offered to three
      patients. CONCLUSIONS: Thyroidectomy was safe for selected patients with
      metastatic disease to the thyroid. Patients with metachronous or renal cell
      metastasis to the thyroid and whose primary tumor is/was treatable may be
      appropriate candidates for resection. Lung cancer metastasis to the thyroid is
      generally an ominous sign.

PMID- 24081802
TI  - Surgical management of sentinel lymph node biopsy outside major nodal basin in
      patients with cutaneous melanoma.
AB  - PURPOSE: To assess the incidence of nonmajor lymphatic basin sentinel nodes in
      patients with cutaneous melanoma in order to propose a correct nomenclature and
      inform appropriate surgical management. METHODS: This was a retrospective review
      of 1,045 consecutive patients with cutaneous melanoma who underwent sentinel
      lymph node biopsy and dynamic lymphoscintigraphy to identify sentinel node site.
      Nonmajor drainage sites were classified as uncommon (located in a minor lymphatic
      basin along the lymphatic drainage to a major classical nodal basin) or interval
      (located anywhere along the lymphatics between the primary tumor site and the
      nearest lymphatic basin) sentinel nodes. RESULTS: Nonclassical sentinel nodes
      were identified in 32 patients (3.0 %). Uncommon sentinel nodes were identified
      in 3.2 % (n = 17) of trunk melanoma primary disease and in 1.5 % (n = 7) of upper
      and lower extremity sites. Interval sentinel nodes were identified in 1.3 % (n =
      7) of trunk primary lesions, with none from upper and lower extremities
      melanomas. The incidence of tumor-positive sentinel nodes was 24.1 % (245 of
      1,013) in classical sites and 12.5 % (4 of 32) in uncommon/interval sites.
      CONCLUSIONS: The definition of uncommon and interval sentinel nodes allows the
      identification of different lymphatic pathways and inform appropriate surgical
      treatment. Wider experience with uncommon/interval sentinel nodes will better
      clarify the clinical implications and surgical management to be adopted in the
      management of uncommon and interval sentinel node sites.

PMID- 24081801
TI  - A systematic review of complications of implant-based breast reconstruction with
      prereconstruction and postreconstruction radiotherapy.
AB  - PURPOSE: To conduct a systematic review of the literature to assess outcomes data
      on complications associated with implant-based breast reconstruction performed
      before or after chest wall radiation to assist in guiding the decision-making
      process for reconstruction of the irradiated breast. METHODS: Studies from a
      PubMed search that met predetermined inclusion criteria were identified and
      included. Complications of interest were low- and high-grade capsular
      contractures, minor and major complications, reconstruction failure rates, and
      reconstruction completion rates. Pooled complication rates were calculated.
      RESULTS: A total of 26 articles were included in the study after screening 1,006
      publications, with 14 studies presenting data on prereconstruction radiation and
      23 studies presenting data on postreconstruction radiation. Complication rates
      evaluated in patients exposed to radiation before or after implant reconstruction
      were not significantly different. Reconstruction failure rates were similar at 19
      and 20 % for pre- and postreconstruction radiation patients, respectively.
      Completion rates were similar at 83 and 80 % for pre- and postreconstruction
      radiation patients, respectively. CONCLUSIONS: Review of the current literature
      suggests similar overall success and failure rates with radiotherapy provided
      both before and after reconstruction. Failure rates in both groups of patients
      are clinically significant when considering implant reconstruction in the setting
      of radiation.

PMID- 24081803
TI  - Prognostic biomarkers in patients with resected cholangiocarcinoma: a systematic
      review and meta-analysis.
AB  - PURPOSE: Biomarkers for patients with resected cholangiocarcinoma (CC) can
      improve staging and may ultimately result in personalized medicine. Studies
      evaluating these biomarkers often have shown inconsistent results. We performed a
      systematic review and meta-analysis to investigate the prognostic value of all
      immunohistochemistry-based markers that have been evaluated in patients with
      resected CC. METHODS: In July 2013, we searched the two main medical literature
      databases: MEDLINE and EMBASE. We extracted hazard ratios (HRs) and associated
      95% confidence intervals (CIs) from the identified studies and performed random
      effects model meta-analyses on overall survival (OS) in accordance with preferred
      reporting items for systematic reviews and meta-analyses statement and reporting
      recommendations for tumor marker prognostic studies (REMARK) guidelines. RESULTS:
      A total of 73 studies, including 4,126 patients studying 77 individual
      biomarkers, met the inclusion criteria. Fourteen studies were graded with a low
      risk of bias. Biomarkers prognostic of OS in pooled analysis included fascin (HR
      2.58; 95% CI 1.19-5.58), EGFR (HR 1.79; 95% CI 1.14-2.8), MUC1 (HR 2.52; 95% CI
      1.49-4.26), MUC4 (HR 2.45; 95% CI 1.56-3.86), and p27 (HR 0.29; 95% CI 0.14-0.6).
      Other markers showed promising results in single studies, including HSP27, Akt,
      HDGF, MUC6, p16, p-4EBP1, S100A4, alpha-SMA, Keratin 903, and TROP2. CONCLUSIONS:
      Meta-analysis demonstrated that the biomarkers fascin, EGFR, MUC1, MUC4, and p27
      are associated with survival in patients with resected CC. Future studies should
      validate these, and other promising biomarkers, and adhere to the REMARK
      guidelines.

PMID- 24081804
TI  - Negative parafibromin staining predicts malignant behavior in atypical
      parathyroid adenomas.
AB  - BACKGROUND: The histopathological criteria for carcinoma proposed by the World
      Health Organization (WHO) are imperfect predictors of the malignant potential of
      parathyroid tumors. Negative parafibromin (PF) and positive protein gene product
      9.5 (PGP9.5) staining are markers of CDC73 mutation and occur commonly in
      carcinoma but rarely in adenomas. We investigated whether PF and PGP9.5 staining
      could be used to predict the behavior of atypical parathyroid adenomas--tumors
      with atypical features that do not fulfill WHO criteria for malignancy. METHODS:
      Long-term outcomes were compared across four groups: group A, WHO-positive
      criteria/PF-negative staining; group B, WHO(+)/PF(+), group C; WHO(-)/PF(-); and
      group D, WHO(-)/PF(+). RESULTS: Eighty-one patients were included in the period
      1999-2012: group A (n = 13), group B (n = 14), group C (n = 21), and group D (n =
      33). Mortality and recurrence rates, respectively, for group A were 15 and 38%,
      for group B 7 and 36%, for group C 0 and 10%, and for group D 0 and 0%. The
      PGP9.5(+) ratios for groups A to D were 85, 78, 71, and 12%, further informing
      prognosis. Five-year disease-free survival for groups A to D were 55, 80, 78, and
      100%, respectively. Tumor recurrence was significantly associated with PF (p =
      0.048) and PGP9.5 (p = 0.003) staining. CONCLUSIONS: Although WHO criteria are
      essential to differentiate parathyroid carcinoma from benign tumors, the presence
      of negative PF staining in an atypical adenoma predicts outcome better, whereas
      PF-positive atypical adenomas do not recur and can be considered benign. PF
      negative atypical adenomas have a low but real recurrence risk and should be
      considered tumors of low malignant potential.

PMID- 24081805
TI  - Validation of the MSKCC and Heng risk criteria models for predicting survival in
      patients with metastatic renal cell carcinoma treated with sunitinib.
AB  - PURPOSE: To validate the Memorial Sloan-Kettering Cancer Center (MSKCC) and Heng
      models with metastatic renal cell carcinoma treated with sunitinib, and to
      investigate prognostic factors in these patients. METHODS: This study included
      106 patients with metastatic renal cell carcinoma who were treated with sunitinib
      from April 2007 to July 2012 including 35 patients who received systemic
      treatment before sunitinib and 71 that were naive to systemic treatment. Patients
      were evaluated using the MSKCC and Heng models, and the significance of several
      prognostic factors were evaluated. RESULTS: The application of the MSKCC and Heng
      risk criteria resulted in stratification into 3 groups (favorable, intermediate,
      and poor risk) with distinctly different overall survival (OS) curves (P < 0.001
      and P < 0.001, respectively), for the pretreated patients (P < 0.001 and P <
      0.001, respectively). The Heng model had slightly better discriminatory ability
      (chi (2) = 30.82, Harrell's C = 0.6895) than the MSKCC model (chi (2) = 25.13,
      Harrell's C = 0.6532). Multivariate analysis revealed that the absence of
      nephrectomy and no hypertension at baseline, along with elevated C-reactive
      protein levels, were independent risk factors for poorer OS. CONCLUSIONS: The
      MSKCC and Heng model were both valid models for predicting OS. The no
      nephrectomy, no hypertension at baseline, and high C-reactive protein levels were
      independently associated with poorer OS.

PMID- 24081806
TI  - Evaluation of two inflammation-based prognostic scores in patients with
      resectable gallbladder carcinoma.
AB  - BACKGROUND: Survival after surgery for gallbladder cancer is generally poor. A
      number of inflammation-based prognostic scores have been established to help
      predict survival after surgery for several types of cancer. The objective of this
      study was to analyze and compare the utility of two inflammation-based prognostic
      scores, the Glasgow prognostic score (GPS) and the neutrophil-to-lymphocyte ratio
      (NLR), for predicting survival in patients with gallbladder cancer after surgery
      with curative intent. METHODS: We retrospectively reviewed the medical records of
      85 patients with histologically confirmed, resectable gallbladder carcinoma
      (GBC), who were to receive curative surgery in our department. Univariate and
      multivariate analyses were performed to evaluate the relationship between the
      variables to overall survival (OS). RESULTS: A significant difference was
      detected in OS in patients with low and high GPS and NLR scores. Univariate
      analyses using clinicopathological characteristics revealed that tumor
      differentiation; tumor invasion; lymph node metastasis; tumor, node, metastasis
      classification system stage; positive margin status; combined common bile duct
      resection; serum levels of C-reactive protein, albumin, carbohydrate antigen 19-9
      (CA19-9), carcinoembryonic antigen, and CA125; white blood cell count; and GPS
      and NLR were all associated with OS. Among these characteristics, multivariate
      analysis demonstrated that a high GPS was independently associated with poorer
      OS, together with tumor invasion, lymph node metastasis, and positive margin
      status. CONCLUSIONS: GPS is superior to NLR with respect to its prognostic value
      for patients with GBC after surgery with curative intent. GPS is not only
      associated with tumor progression but is also an independent marker of poor
      prognosis.

PMID- 24081807
TI  - Cause of death from liver metastases in colorectal cancer.
AB  - BACKGROUND: Surgically directed therapy for liver metastases from colorectal
      cancer (CRC) has received substantial attention in the literature as a major
      focus of treatment for metastatic CRC. It is presumed, but not proven, that liver
      metastases are a major threat to life. This study examined the course of a cohort
      of consecutive patients who died with CRC to determine the role played by the
      presence of liver metastases. METHODS: This is single-institution retrospective
      observational study involved all patients who died of CRC. Records were examined
      and imaging studies reviewed to determine the extent of liver and extrahepatic
      metastases in these patients. Overall survival in patients with and without liver
      metastases and those in whom liver metastases were thought to contribute to death
      was determined. RESULTS: After patient exclusions, the study population totaled
      121 patients. There were 75 patients (62%) with liver metastases at death. In 40
      of 75 (53%) patients, the liver metastases contributed to the patients' death. In
      46 of 121 patients (38%), metastatic disease did not include liver metastases.
      Overall survival in patients with and without liver metastases (median survival
      12 vs. 8.5 months, p = 0.089) and in those whose liver metastases did or did not
      contribute to death (median survival 11.5 vs. 14 months, p = 0.361) was not
      significant. CONCLUSIONS: The presence of liver metastases seemed to contribute
      to death in approximately half of the study patients, although there did not
      appear to be a survival disadvantage in these patients.

PMID- 24081808
TI  - Laparoscopic right hepatectomy extended to middle hepatic vein after right portal
      vein embolization.
AB  - BACKGROUND: Laparoscopic right hepatectomy (LRH) is a complex but feasible
      procedure. Preoperative portal vein embolization (PVE) can add difficulties that
      warrant particular technical modifications. A LRH extended to middle hepatic vein
      after PVE is presented, with special attention paid to specific operative
      findings and to useful technical modifications. METHODS: A 62-year-old female
      patient with a body mass index of 30.5 kg/m(2) was diagnosed with a 3-cm
      unresectable centrally located intrahepatic cholangiocarcinoma with infiltration
      of the retrohepatic vena cava, segment VII portal branch, and adjacent to the
      middle hepatic vein and portal bifurcation. After four cycles of GEMOX, partial
      response was observed, disappearing vascular infiltration. PVE was required to
      perform an extended LRH. Consequently, during pedicle dissection, significant
      inflammation was found in the vicinity of the right portal vein. Thus, the
      section of the portal and biliary elements was delayed until the transection of
      the parenchyma reached the hilum. The opening of the parenchyma improved
      exposure, allowing the safe management of these structures individually. RESULTS:
      The total operative time was 438 min. Three periods of 15-min pedicle occlusion
      resulted in <100 ml bleeding. Hospital stay was 4 days. Pathological examination
      revealed residual cholangiocarcinoma with intense posttreatment changes (pT1) and
      tumor-free margins. After an 18-month follow-up, the patient was alive and free
      of disease. CONCLUSIONS: LRH is feasible and safe, even after PVE. Nevertheless,
      periportal inflammation can hinder hilar dissection. In this setting, delaying
      section of portal and biliary elements until parenchymal transection reaches the
      hilar region may result in a useful and safe strategy.

PMID- 24081809
TI  - Acute brain ischemia as a complication of the Ehlers-Danlos syndrome, the case
      series.
AB  - Vascular type of Ehlers-Danlos syndrome involves many severe complications
      leading not only to organ-specific symptoms but often ends in a sudden death. The
      aim of this paper was to present a diagnostic possibilities and its efficiency
      rate in patients with vascular complications of Ehlers-Danlos syndrome who
      suffered from artery dissection resulting in acute brain or limb ischemia. We
      analysed three patients with diagnosed Ehlers-Danlos syndrome who were referred
      to radiology department for diagnostic imaging of affected vascular beds, each
      experienced brain ischemia. The paper also aims at offering some general
      recommendations for patients suffering from possible complications of type IV
      Ehlers-Danlos syndrome basing on our own experience and available literature
      data. 

PMID- 24081810
TI  - Unique structural changes in calcium-bound calmodulin upon interaction with
      protein 4.1R FERM domain: novel insights into the calcium-dependent regulation of
      4.1R FERM domain binding to membrane proteins by calmodulin.
AB  - Calmodulin (CaM) binds to the FERM domain of 80 kDa erythrocyte protein 4.1R
      (R30) independently of Ca(2+) but, paradoxically, regulates R30 binding to
      transmembrane proteins in a Ca(2+)-dependent manner. We have previously mapped a
      Ca(2+)-independent CaM-binding site, pep11 (A(264)KKLWKVCVEHHTFFR), in 4.1R FERM
      domain and demonstrated that CaM, when saturated by Ca(2+) (Ca(2+)/CaM),
      interacts simultaneously with pep11 and with Ser(185) in A(181)KKLSMYGVDLHKAKD
      (pep9), the binding affinity of Ca(2+)/CaM for pep9 increasing dramatically in
      the presence of pep11. Based on these findings, we hypothesized that pep11
      induced key conformational changes in the Ca(2+)/CaM complex. By differential
      scanning calorimetry analysis, we established that the C-lobe of CaM was more
      stable when bound to pep11 either in the presence or absence of Ca(2+). Using
      nuclear magnetic resonance spectroscopy, we identified 8 residues in the N-lobe
      and 14 residues in the C-lobe of pep11 involved in interaction with CaM in both
      of presence and absence of Ca(2+). Lastly, Kratky plots, generated by small-angle
      X-ray scattering analysis, indicated that the pep11/Ca(2+)/CaM complex adopted a
      relaxed globular shape. We propose that these unique properties may account in
      part for the previously described Ca(2+)/CaM-dependent regulation of R30 binding
      to membrane proteins. 

PMID- 24081811
TI  - Long-term treatment after preoperative high-dose chemotherapy in a lactating
      breast cancer patient.
AB  - Breast cancer during lactation is very rare, accounting for <3% of all breast
      cancers. Its diagnosis and treatment is often delayed during pregnancy. We report
      a case of female lactating breast carcinoma in a 29-year old patient. The disease
      was stage IIIB (T4N1M0). The patient received preoperative induction chemotherapy
      and high-dose chemotherapy with peripheral blood stem cell support, followed by
      adjuvant chemotherapy and endocrine therapy. The metastases were detected 17
      months after operation, palliative treatment including different chemotherapy for
      60 cycles, locoregional radiotherapy and endocrine therapy. The total number of
      cycles of chemotherapy was 67, and the survival time was 118 months. We discuss
      the diagnosis and treatment options for breast cancer during lactation, based on
      a literature review.

PMID- 24081812
TI  - EGF enhances ADSCs secretion via ERK and JNK pathways.
AB  - The objective of this work was to study the effect of epidermal growth factor
      (EGF) induced secretions of angiogenesis factors in adipose-derived stem cells
      (ADSCs) and the involvement of mitogen-activated protein kinases (MAPK). ADSCs
      were cultured and ELISA assays were performed to quantify the vascular
      endothelial growth factor, the hepatocyte growth factor, and the stromal derived
      factor-1 in ADSC-conditioned medium before and after EGF treatments and after
      pharmacological inhibition of MAPKs with PD98059, SB203580, and SP600125. The
      tube formation assay was used to test the effects of EGF treated and inhibitor
      treated ADSCs on the human umbilical vein endothelial cells (HUVECs) tube
      formation. Liposuction was applied and ADSCs were cultured successfully. The
      ADSCs released a variety of angiogenic factors, with the EGF treatments enhancing
      secretions and promoting the HUVEC tube formation. The MAPK inhibitors PD98059
      and SP600125 increased the paracrine to promote tubular formation, while the
      SB203580 played an opposite role. In conclusion, (1) the in vitro cultured ADSCs
      secrete various angiogenic factors and the EGF amplifies the secretion and can
      enhance the ADSCs on the HUVEC tube formation. (2) ERK1/2 and JNK pathway may be
      involved in the enhanced secretion capacity of ADSCs while the p38 pathway may
      exert an opposite effect. 

PMID- 24081813
TI  - Intravertebral pneumatocysts of the cervical spine.
AB  - INTRODUCTION: The aim of this study was to investigate the prevalence of
      intravertebral pneumatocyst (IVP) of the cervical spine by age group, compared
      with that of intradiscal vacuum (IDV). METHODS: We investigated 500 consecutive
      patients who underwent cervical computed tomography (CT) from May 2012 to May
      2013 for various indications. CT datasets were assessed for the presence of IVPs
      and IDVs with stratification by age. RESULTS: IVPs of the cervical spine were
      detected in 8 % (7 of 86 subjects) of patients in their forties or below, 30 %
      (23 of 75) in their fifties, 49 % (67 of 136) in their sixties, 55 % (76 of 137)
      in their seventies, and 60 % (40 of 66) in their eighties or over. IDVs of the
      cervical spine were detected in 6, 25, 48, 54, and 57 %, respectively.
      Coexistence of both phenomena was identified in 4, 17, 33, 40, and 43 %,
      respectively. CONCLUSION: IVPs of the cervical spine are a common incidental
      finding, increasing in prevalence with age and more common than IDV in all age
      groups.

PMID- 24081815
TI  - Evaluation of an alternate method for sampling benthic macroinvertebrates in low
      gradient streams sampled as part of the National Rivers and Streams Assessment.
AB  - Benthic macroinvertebrates are sampled in streams and rivers as one of the
      assessment elements of the US Environmental Protection Agency's National Rivers
      and Streams Assessment. In a 2006 report, the recommendation was made that
      different yet comparable methods be evaluated for different types of streams
      (e.g., low gradient vs. high gradient). Consequently, a research element was
      added to the 2008-2009 National Rivers and Streams Assessment to conduct a side
      by-side comparison of the standard macroinvertebrate sampling method with an
      alternate method specifically designed for low-gradient wadeable streams and
      rivers that focused more on stream edge habitat. Samples were collected using
      each method at 525 sites in five of nine aggregate ecoregions located in the
      conterminous USA. Methods were compared using the benthic macroinvertebrate
      multimetric index developed for the 2006 Wadeable Streams Assessment. Statistical
      analysis did not reveal any trends that would suggest the overall assessment of
      low-gradient streams on a regional or national scale would change if the
      alternate method was used rather than the standard sampling method, regardless of
      the gradient cutoff used to define low-gradient streams. Based on these results,
      the National Rivers and Streams Survey should continue to use the standard field
      method for sampling all streams. 

PMID- 24081814
TI  - Phycobilisome: architecture of a light-harvesting supercomplex.
AB  - The phycobilisome (PBS) is an extra-membrane supramolecular complex composed of
      many chromophore (bilin)-binding proteins (phycobiliproteins) and linker
      proteins, which generally are colorless. PBS collects light energy of a wide
      range of wavelengths, funnels it to the central core, and then transfers it to
      photosystems. Although phycobiliproteins are evolutionarily related to each
      other, the binding of different bilin pigments ensures the ability to collect
      energy over a wide range of wavelengths. Spatial arrangement and functional
      tuning of the different phycobiliproteins, which are mediated primarily by linker
      proteins, yield PBS that is efficient and versatile light-harvesting systems. In
      this review, we discuss the functional and spatial tuning of phycobiliproteins
      with a focus on linker proteins. 

PMID- 24081816
TI  - The impact of stormwater treatment areas and agricultural best management
      practices on water quality in the Everglades Protection Area.
AB  - Half of the original Everglades system has been lost to drainage and development.
      What remains is included within the boundaries of the Everglades Protection Area
      (EPA), comprised of three Water Conservation Areas (WCAs) and Everglades National
      Park (Park). Inflows to the EPA contain elevated nutrient concentrations. Best
      management practices (BMPs) were implemented and six large wetlands called
      stormwater treatment areas (STAs) were constructed to improve water quality. We
      analyzed water quality in the WCAs and Park and performed an economic analysis of
      the STAs to remove nutrients from EPA inflows. In general, nutrient
      concentrations in all WCAs were higher during the pre-STA period than after the
      STAs became operational. In WCA2 and the Park, total phosphorus (TP) trends
      showed more negative slopes prior, as compared to after, the STAs became
      operational. These results suggest that BMPs lead to large initial decreases in
      nutrient export resulting in improved downstream water quality. A preliminary
      economic analysis shows that operation and management of the STAs are complicated
      and cost intensive. Comparing the cost of phosphorus (P) removal from water
      entering the EPA using BMPs and STAs may not currently be viable. BMPs prevent P
      from being applied to, or leaving from agricultural fields while STAs remove P
      from stormwater. We expect nutrient concentrations in water flowing into and out
      of the STAs to decline as both BMPs and STAs become more effective. We suggest an
      economic analysis of BMPs, STAs, and other potential approaches to determine the
      most cost-effective methods to reduce nutrient concentrations and related
      stressors affecting the Everglades. 

PMID- 24081817
TI  - What went wrong with the quality and safety agenda? An essay by Michael Buist and
      Sarah Middleton.

PMID- 24081818
TI  - Indications for and use of inferior vena cava filters in the preoperative phase.

PMID- 24081819
TI  - No trust will get foundation status until it has gone through CQC inspection
      regime, Monitor says.

PMID- 24081820
TI  - Development of validated stability indicating assay method for simultaneous
      estimation of metformin hydrochloride and vildagliptin by RP-HPLC.
AB  - A simple, precise and stability-indicating HPLC method was developed and
      validated for the simultaneous determination of metformin hydrochloride (MET) and
      vildagliptin (VLG) in pharmaceutical dosage forms. The method involves use of
      easily available inexpensive laboratory reagents. The separation was achieved on
      Grace Cyano column (250 mm*4.6 mm) 5 um with isocratic flow. The mobile phase was
      pumped at a flow rate of 1.0 mL/min, consisted of 25 mM ammonium bicarbonate
      buffer and acetonitrile (65:35, v/v). The UV detection was carried out at 207 nm.
      A linear response was observed over the concentration range of 25-125 ug/mL for
      MET and 50-250 ug/mL for VLG respectively. Limit of detection and limit of
      quantification for MET were 0.36 ug/mL and 1.22 ug/mL, and for VLG were 0.75
      ug/mL and 2.51 ug/mL respectively. The method was successfully validated in
      accordance to ICH guidelines acceptance criteria for specificity, linearity,
      accuracy, precision, robustness, and system suitability. Individual drugs (MET
      and VLG) were exposed to thermal, photolytic, hydrolytic and oxidative stress
      conditions. The resultant stressed samples were analyzed by the proposed method.
      The method gave high resolution among the degradation products and the analytes.
      The peak purity of analyte peak in the stressed samples was confirmed by photo
      diode array detector. The proposed method was successfully applied for the
      quantitative analysis of MET and VLG in tablet dosage form, which will help to
      improve quality control and contribute to stability studies of pharmaceutical
      tablets containing these drugs.

PMID- 24081821
TI  - Comet-FISH for the evaluation of plant DNA damage after mutagenic treatments.
AB  - The aim of this study was to perform a comparative investigation of the actions
      of three mutagens that are widely used in plant mutagenesis using the comet-FISH
      technique. The comet-FISH technique was used for the analysis of DNA damage and
      the kinetics of repair within specific DNA sequences. FISH with rDNA and
      telomeric/centromeric DNA probes was applied to comets that were obtained from an
      alkaline/neutral comet assay. Migration within specific DNA sequences was
      analysed after treatment with two chemical mutagens-maleic hydrazide (MH) and N
      nitroso-N-methylurea (MNU), and gamma-rays. Barley was used as a model plant in
      this study. The possible utility of specific DNA sequences in a comparative
      assessment of the distribution of DNA damage within a plant genome was evaluated.
      This study proved that the comet-FISH technique is suitable for a detailed
      quantification of DNA damage and repair within specific DNA sequences in plant
      mutagenesis. The analysis of FISH signals demonstrated that the involvement of
      specific DNA sequences in DNA damage was different and was dependent on the
      mutagen used. We showed that 5S rDNA and telomeric DNA sequences are more
      sensitive to mutagenic treatment, which was expressed by a stronger fragmentation
      and migration in comparison to the other probes used in the study. We found that
      5S rDNA and telomeric DNA probes are more suitable for testing the genotoxicity
      of environmental factors. A comparison of the involvement of specific chromosome
      domains in direct DNA breakage/repair and in chromosome aberration formation
      after mutagen treatment indicates the compatibility of the results. 

PMID- 24081822
TI  - Isolation and molecular analysis of genes Stpk-V2 and Stpk-V3 homologous to
      powdery mildew resistance gene Stpk-V in a Dasypyrum villosum accession and its
      derivatives.
AB  - Wheat-Dasypyrum villosum translocated chromosomes T6V#2S*6AL and T6V#4S*6DL are
      known to confer excellent resistance to wheat powdery mildew (PM). However, it is
      difficult to distinguish the two sources of PM resistance genes through multi
      pathotype testing because to date no virulence for them has been found. To reveal
      the relationship between the PM resistance genes from the two translocations, the
      sequence of the Stpk-V gene, a key member of powdery mildew resistance locus
      Pm21, was used as a reference to isolate homologous genes from a D. villosum
      accession No.1026 and its derivatives 6V#4(6D) disomic substitution (DS) line
      RW15 and T6V#4S*6DL translocation line Pm97033. Two genes Stpk-V2 and Stpk-V3
      were cloned from No.1026. Sequence alignment showed that Stpk-V2 and Stpk-V3
      shared 98.2 % and 96.2 % of their DNA and 99.3 % and 100 % of their amino acids
      in identity with Stpk-V. Compared with Stpk-V, a 22-bp direct sequence repeat and
      a miniature inverted-repeat transposable element (MITE) were found in the intron
      4 of Stpk-V2 and Stpk-V3, respectively. However, Stpk-V2 was not present in DS
      line RW15 and translocation line Pm97033 based on the PCR result, indicating that
      Stpk-V2 did not contribute to the PM resistance of RW15 and Pm97033. In the
      promoter region, a 78-bp insertion was found not only in Stpk-V2 and Stpk-V3, but
      also in its orthologous gene Stpk-A of wheat. In addition, there was a 17 bp/8 bp
      deletion/insertion in the putative promoter of Stpk-V3 in comparison with that of
      Stpk-V/Stpk-V2. Real-time quantitative RT-PCR analysis indicated that the
      expression levels of Stpk-V and Stpk-V3 genes in the translocation lines were
      induced by the pathogen, but Stpk-V had a higher expression level than Stpk-V3 at
      12 h after inoculation with Bgt. The diversity of Stpk-V gene will help to
      explore new resistance genes to PM in D. villosum for wheat breeding. 

PMID- 24081823
TI  - Dichorhavirus: a proposed new genus for Brevipalpus mite-transmitted, nuclear,
      bacilliform, bipartite, negative-strand RNA plant viruses.
AB  - Orchid fleck virus (OFV) is an unassigned negative-sense, single-stranded (
      )ssRNA plant virus that was previously suggested to be included in the family
      Rhabdoviridae, order Mononegavirales. Although OFV shares some biological
      characteristics, including nuclear cytopathological effects, gene order, and
      sequence similarities, with nucleorhabdoviruses, its taxonomic status is unclear
      because unlike all mononegaviruses, OFV has a segmented genome and its particles
      are not enveloped. This article analyses the available biological, physico
      chemical, and nucleotide sequence evidence that seems to indicate that OFV and
      several other Brevipalpus mite-transmitted short bacilliform (-)ssRNA viruses are
      likely related and may be classified taxonomically in novel species in a new free
      floating genus Dichorhavirus. 

PMID- 24081824
TI  - Investigating a crow die-off in January-February 2011 during the introduction of
      a new clade of highly pathogenic avian influenza virus H5N1 into Bangladesh.
AB  - We investigated unusual crow mortality in Bangladesh during January-February 2011
      at two sites. Crows of two species, Corvus splendens and C. macrorhynchos, were
      found sick and dead during the outbreaks. In selected crow roosts, morbidity was
      ~1 % and mortality was ~4 % during the investigation. Highly pathogenic avian
      influenza virus H5N1 clade 2.3.2.1 was isolated from dead crows. All isolates
      were closely related to A/duck/India/02CA10/2011 (H5N1) with 99.8 % and
      A/crow/Bangladesh/11rs1984-15/2011 (H5N1) virus with 99 % nucleotide sequence
      identity in their HA genes. The phylogenetic cluster of Bangladesh viruses
      suggested a common ancestor with viruses found in poultry from India, Myanmar and
      Nepal. Histopathological changes and immunohistochemistry staining in brain,
      pancreas, liver, heart, kidney, bursa of Fabricius, rectum, and cloaca were
      consistent with influenza virus infection. Through our limited investigation in
      domesticated birds near the crow roosts, we did not identify any samples that
      tested positive for influenza virus A/H5N1. However, environmental samples
      collected from live-bird markets near an outbreak site during the month of the
      outbreaks tested very weakly positive for influenza virus A/H5N1 in clade 2.3.2.1
      specific rRT-PCR. Continuation of surveillance in wild and domestic birds may
      identify evolution of new avian influenza virus and associated public-health
      risks. 

PMID- 24081825
TI  - Inhibitory effects of curcumin on dengue virus type 2-infected cells in vitro.
AB  - Curcumin, a traditional Chinese and Indian treatment for many diseases, has
      recently been found to alter the in vitro infection processes of various viruses,
      including hepatitis C virus, human immunodeficiency virus, coxsackievirus, and
      Japanese encephalitis virus. The present study evaluated the cellular effects of
      curcumin in an in vitro (cellular) infection model of dengue virus. Within a dose
      range of 10 to 30 MUM and a treatment period of 24 hours, the cytotoxicity of
      curcumin was low, as determined by MTT assays. Cells infected with dengue virus
      type 2 at a multiplicity of infection of 5 were treated with various
      concentrations of curcumin or the proteasome inhibitor MG132. Plaque assays,
      immunofluorescence analysis, western blots, and in-cell western assays were then
      performed. Treatment with 10, 15, and 20 MUM curcumin decreased the number of
      plaques produced, caused an intracellular accumulation of viral proteins, and
      increased the level of Lys48 ubiquitin-conjugated proteins. At 20 MUM curcumin,
      changes in cell and nuclear morphology and alterations in the actin cytoskeleton
      were also observed. Treatment with MG132 also reduced plaque production. These
      results show that curcumin can interfere with the infection processes of dengue
      virus and that this interference may not occur through direct effects on viral
      particle production but may result from curcumin's effects on various cellular
      systems such as the cytoskeleton, the ubiquitin-proteasome system, or the
      apoptosis process. 

PMID- 24081826
TI  - Preparation of transgenic Dunaliella salina for immunization against white spot
      syndrome virus in crayfish.
AB  - Although a white spot syndrome virus (WSSV) subunit vaccine could significantly
      enhance the immune response and benefit the shrimp host, its practical
      application is currently not feasible because of drawbacks in existing expression
      systems. We generated a transgenic Dunaliella salina (D. salina) strain by
      introducing the WSSV VP28 gene to produce a novel oral WSSV subunit vaccine.
      Following transformation of D. salina, VP28 gene expression was assessed by
      reverse transcription polymerase chain reaction (RT-PCR) assays, enzyme-linked
      immunosorbent assays (ELISAs), and western blot analysis. The RT-PCR results
      indicated that the VP28 gene was successfully expressed in D. salina cells. The
      presence of recombinant VP28 proteins with natural bioactivity was confirmed by
      western blot analysis and ELISA. Animal vaccination experiments indicated that
      transgenic D. salina can induce protection against WSSV by oral delivery in
      crayfish. Our findings indicate that the VP28 gene can be successfully expressed
      in transgenic D. salina and can be applied as an oral vaccine to protect crayfish
      against WSSV. We have demonstrated that it is feasible to produce an oral vaccine
      using D. salina, and thereby provide a new method for controlling other viral
      diseases in crustaceans. 

PMID- 24081827
TI  - Automatic metaphor processing in adults with Asperger syndrome: a metaphor
      interference effect task.
AB  - This paper investigates automatic processing of novel metaphors in adults with
      Asperger Syndrome (AS) and typically developing controls. We present an
      experiment combining a semantic judgment task and a recognition task. Four types
      of sentences were compared: Literally true high-typical sentences, literally true
      low-typical sentences, apt metaphors, and scrambled metaphors (literally false
      sentences which are not readily interpretable as metaphors). Participants were
      asked to make rapid decisions about the literal truth of such sentences. The
      results revealed that AS and control participants showed significantly slower RTs
      for metaphors than for scrambled metaphors and made more mistakes in apt
      metaphoric sentences than in scrambled metaphors. At the same time, there was
      higher recognition of apt metaphors compared with scrambled metaphors. The
      findings indicate intact automatic metaphor processing in AS and replicate
      previous findings on automatic metaphor processing in typically developing
      individuals. 

PMID- 24081828
TI  - Continuing need for and provision of a service for non-standard implant removal.
AB  - BACKGROUND AND METHODOLOGY: Information is presented on the management of women
      referred to a sexual health service during a 1-year period for management of a
      non-palpable contraceptive implant or of a palpable implant considered unsuitable
      for routine removal. RESULTS: Fifty-two women were referred. Thirty-four implants
      were non-palpable and their depth on ultrasound ranged from 2.7 to 12mm.
      Seventeen were fully or partly palpable and their depth ranged from 3mm or less
      (16 cases) to 5.6&emsp14;mm (one case). Nine had had previous failed attempts at
      removal, including three with two previous failed attempts. Three implants were
      located at sites other than the medial aspect of the arm, and were associated
      with long localisation times. Forty-seven implants were removed at a one-stop
      clinic appointment through a 2-3mm incision using ring forceps. The mean time for
      removal from making the incision to complete extraction was 4.8&emsp14;minutes.
      Three cases judged to be of higher risk were removed under local anaesthesia in
      theatre through a 15mm incision. These included the only case where removal was
      attempted unsuccessfully in the outpatient clinic. Seven of the implants were
      Nexplanon((r)), including four cases seen during the last month of data
      collection. CONCLUSIONS: Removal with the technique described is rapid, with an
      average time of 4-5 minutes, and less than 10minutes in >90% of cases.
      Preliminary indications suggest that the introduction of Nexplanon has not
      resolved the problem of deep implant insertion. Based on our experience we
      suggest criteria for centres providing removal of deep implants.

PMID- 24081830
TI  - Brainography: an atlas-independent surface and network rendering tool for neural
      connectivity visualization.

PMID- 24081829
TI  - Classifying lower extremity muscle fatigue during walking using machine learning
      and inertial sensors.
AB  - Fatigue in lower extremity musculature is associated with decline in postural
      stability, motor performance and alters normal walking patterns in human
      subjects. Automated recognition of lower extremity muscle fatigue condition may
      be advantageous in early detection of fall and injury risks. Supervised machine
      learning methods such as support vector machines (SVMs) have been previously used
      for classifying healthy and pathological gait patterns and also for separating
      old and young gait patterns. In this study we explore the classification
      potential of SVM in recognition of gait patterns utilizing an inertial
      measurement unit associated with lower extremity muscular fatigue. Both kinematic
      and kinetic gait patterns of 17 participants (29 +/- 11 years) were recorded and
      analyzed in normal and fatigued state of walking. Lower extremities were fatigued
      by performance of a squatting exercise until the participants reached 60% of
      their baseline maximal voluntary exertion level. Feature selection methods were
      used to classify fatigue and no-fatigue conditions based on temporal and
      frequency information of the signals. Additionally, influences of three different
      kernel schemes (i.e., linear, polynomial, and radial basis function) were
      investigated for SVM classification. The results indicated that lower extremity
      muscle fatigue condition influenced gait and loading responses. In terms of the
      SVM classification results, an accuracy of 96% was reached in distinguishing the
      two gait patterns (fatigue and no-fatigue) within the same subject using the
      kinematic, time and frequency domain features. It is also found that linear
      kernel and RBF kernel were equally good to identify intra-individual fatigue
      characteristics. These results suggest that intra-subject fatigue classification
      using gait patterns from an inertial sensor holds considerable potential in
      identifying "at-risk" gait due to muscle fatigue.

PMID- 24081831
TI  - Identifying hospital-wide harm: a set of ICD-9-CM-coded conditions associated
      with increased cost, length of stay, and risk of mortality.
AB  - This study identifies an expanded set of hospital-acquired conditions (HACs),
      using the Present-On-Admission (POA) indicator and secondary diagnoses present on
      International Classification of Diseases, Ninth Revision, Clinical Modification
      (ICD-9-CM)-coded discharge abstracts and evaluates their association with
      mortality, length of stay (LOS), and cost. A sample of 500 000 de-identified ICD
      9-CM-coded discharge abstracts was randomly drawn from a data set of 11 million.
      A total of 138 secondary condition clusters were identified as potential
      inpatient complications (PICs). Regression modeling was used to determine
      marginal association of each PIC with mortality, LOS, and cost. In all, 16% of
      hospitalized patients developed 1 or more of these conditions while in the
      hospital compared with less than 1% of inpatients experiencing HACs defined by
      the Centers for Medicare and Medicaid Services. Also, 74 PICs were associated
      with seriously higher mortality rates (5 excess deaths per 1000), significantly
      LOS (0.4 extra days per discharge), and significantly higher costs (an extra
      $1000 per discharge). 

PMID- 24081832
TI  - Characterization of capsaicinoids and antioxidants in hot peppers as influenced
      by hybrid and harvesting stage.
AB  - Studies were conducted to investigate the accumulation pattern of capsaicinoids
      and antioxidants such as carotenoids, ascorbic acid and phenolic compounds in
      three hot pepper hybrids at five different harvesting stages: immature green,
      mature green, color break, red ripe and dried fruit. Capsaicin and
      dihydrocapsaicin contents were maximum at mature green stage in both Sky Red
      (61.30 and 43.76 mg/100 g) and Wonder King (43.93 and 26.16 mg/100 g) hybrids,
      whereas Maha hybrid reached top values at color break stage (39.13 and 24.20
      mg/100 g). The accumulation of total carotenoids showed an 8-fold increase from
      red ripe (12 mg/100 g) to dried fruit stage (96 mg/100 g), while a noticeable
      decline by 76 % was observed for ascorbic acid at same harvesting stages (150 vs.
      36 mg/100 g, respectively). The three hot pepper hybrids showed great variations
      in the evolution of total phenolic contents during harvesting stages. Overall,
      the mature green stage was ideal to acquire maximum pungency due to
      capsaicinoids, while peppers at red ripe stage were best sources of ascorbic acid
      and dried fruits contained higher levels of total carotenoids. 

PMID- 24081834
TI  - Misperceptions of ovarian cancer risk in women at increased risk for hereditary
      ovarian cancer.
AB  - This study assessed the sociodemographic, medical and psychological predictors of
      accuracy of perceived risk in women at increased genetic risk for ovarian cancer.
      Women participating in a large cohort study who were at increased risk of ovarian
      and fallopian tube cancer, had no personal history of cancer and had >=1 ovary in
      situ at cohort enrollment, were eligible. Women completed self-administered
      questionnaires and attended an interview at enrollment. Of 2,868 women unaffected
      with cancer at cohort enrollment, 561 were eligible. 335 women (59.8 %)
      overestimated their ovarian cancer risk, while 215 women (38.4 %) accurately
      estimated their risk, and 10 (1.8 %) underestimated it. Women who did not know
      their mutation status were more likely to overestimate their risk (OR 1.74, 95 %
      CI 1.10, 2.77, p = 0.018), as were those with higher cancer-specific anxiety (OR
      1.05, 95 % CI 1.02, 1.08, p < 0.001) and/or a mother who had been diagnosed with
      ovarian cancer (OR 1.98, 95 % CI 1.23, 3.18, p = 0.005). Amongst the group of
      women who did not know their mutation status, 63.3 % overestimated their risk and
      the mean perceived lifetime risk of developing ovarian cancer was 42.1 %,
      compared to a mean objective risk of 6.4 %. A large number of women at increased
      risk for ovarian cancer overestimate their risk. This is of concern especially in
      women who are at moderately increased risk only; for this sub-group of women,
      interventions are needed to reduce potentially unnecessary psychological distress
      and minimise engagement in unnecessary surgery or screening.

PMID- 24081835
TI  - Constant-momentum acceleration time-of-flight mass spectrometry with energy
      focusing.
AB  - Fundamental aspects of constant-momentum acceleration time-of-flight mass
      spectrometry (CMA-TOFMS) are explored as a means to improve mass resolution. By
      accelerating all ions to the same momentum rather than to the same energy, the
      effects of the initial ion spatial and energy distributions upon the total ion
      flight time are decoupled. This decoupling permits the initial spatial
      distribution of ions in the acceleration region to be optimized independently,
      and energy focus, including ion turn-around-time error, to be accomplished with a
      linear-field reflectron. Constant-momentum acceleration also linearly disperses
      ions across time according to mass-to-charge (m/z) ratio, instead of the
      quadratic relationship between flight time and m/z found in conventional TOFMS.
      Here, CMA-TOFMS is shown to achieve simultaneous spatial and energy focusing over
      a selected portion of the mass spectrum. An orthogonal-acceleration time-of
      flight system outfitted with a reduced-pressure DC glow discharge (GD) ionization
      source is used to demonstrate CMA-TOFMS with atomic ions. The influence of
      experimental parameters such as the amplitude and width of the time-dependent CMA
      pulse on mass resolution is investigated, and a useful CMA-TOFMS focusing window
      of 2 to 18 Da is found for GD-CMA-TOFMS. 

PMID- 24081837
TI  - Reduced brain/serum glucose ratios predict cerebral metabolic distress and
      mortality after severe brain injury.
AB  - BACKGROUND: The brain is dependent on glucose to meet its energy demands. We
      sought to evaluate the potential importance of impaired glucose transport by
      assessing the relationship between brain/serum glucose ratios, cerebral metabolic
      distress, and mortality after severe brain injury. METHODS: We studied 46
      consecutive comatose patients with subarachnoid or intracerebral hemorrhage,
      traumatic brain injury, or cardiac arrest who underwent cerebral microdialysis
      and intracranial pressure monitoring. Continuous insulin infusion was used to
      maintain target serum glucose levels of 80-120 mg/dL (4.4-6.7 mmol/L). General
      linear models of logistic function utilizing generalized estimating equations
      were used to relate predictors of cerebral metabolic distress (defined as a
      lactate/pyruvate ratio [LPR] >= 40) and mortality. RESULTS: A total of 5,187
      neuromonitoring hours over 300 days were analyzed. Mean serum glucose was 133
      mg/dL (7.4 mmol/L). The median brain/serum glucose ratio, calculated hourly, was
      substantially lower (0.12) than the expected normal ratio of 0.40 (brain 2.0 and
      serum 5.0 mmol/L). In addition to low cerebral perfusion pressure (P = 0.05) and
      baseline Glasgow Coma Scale score (P < 0.0001), brain/serum glucose ratios below
      the median of 0.12 were independently associated with an increased risk of
      metabolic distress (adjusted OR = 1.4 [1.2-1.7], P < 0.001). Low brain/serum
      glucose ratios were also independently associated with in-hospital mortality
      (adjusted OR = 6.7 [1.2-38.9], P < 0.03) in addition to Glasgow Coma Scale scores
      (P = 0.029). CONCLUSIONS: Reduced brain/serum glucose ratios, consistent with
      impaired glucose transport across the blood brain barrier, are associated with
      cerebral metabolic distress and increased mortality after severe brain injury.

PMID- 24081839
TI  - Simpler, faster, more accurate melanocytic lesion segmentation through MEDS.
AB  - We present a new technique for melanocytic lesion segmentation, Mimicking Expert
      Dermatologists' Segmentations (MEDS), and extensive tests of its accuracy, speed,
      and robustness. MEDS combines a thresholding scheme reproducing the cognitive
      process of dermatologists with a number of optimizations that may be of
      independent interest. MEDS is simple, with a single parameter tuning its
      "tightness". It is extremely fast, segmenting medium-resolution images in a
      fraction of a second even with the modest computational resources of a cell phone
      an improvement of an order of magnitude or more over state-of-the-art techniques.
      And it is extremely accurate: very experienced dermatologists disagree with its
      segmentations less than they disagree with the segmentations of state-of-the-art
      techniques, and in fact less than they disagree with the segmentations of
      dermatologists of moderate experience.

PMID- 24081838
TI  - Probabilistic estimation of mechanical properties of biomaterials using atomic
      force microscopy.
AB  - Nanoindentation using contact-mode atomic force microscopy (AFM) has emerged as a
      powerful tool for effective material characterization of a wide variety of
      biomaterials across multiple length scales. However, the interpretation of force
      indentation experimental data from AFM is subject to some debate. Uncertainties
      in AFM data analysis stems from two primary sources: The exact point of contact
      between the AFM probe and the biological specimen and the variability in the
      spring constant of the AFM probe. While a lot of attention has been directed
      toward addressing the contact-point uncertainty, the effect of variability in the
      probe spring constant has not received sufficient attention. In this paper, we
      report on an error-in-variables-based Bayesian change-point approach to quantify
      the elastic modulus of human breast tissue samples after accounting for
      variability in both contact point and the probe spring constant. We also discuss
      the efficacy of our approach to a wide range of hyperparameter values using a
      sensitivity analysis.

PMID- 24081840
TI  - Endometrial ablation as a treatment for heavy menstrual bleeding.
AB  - Until the 1980s, the only available definitive treatment for heavy menstrual
      bleeding (HMB) was hysterectomy, usually performed abdominally, and sometimes
      vaginally. Historically, multiple attempts to effect ablation of the endometrium
      were developed, including using steam and toxic chemicals, such as chloriquine.
      The advent of Nd-YAG laser endometrial ablation in the mid-1980s offered the
      first minimally invasive alternative to hysterectomy for the treatment of HMB. Nd
      YAG ablation, however, was expensive, cumbersome, and difficult to learn;
      rollerball resectoscopic ablation was initially described by DeCherney in 1987,
      and soon overtook laser as the main method of ablation, although adoption
      continued to be limited because of the hysteroscopic skills necessary to perform
      the technique were not widely available. In 1994, the first "global" endometrial
      ablation, the ThermachoiceTM (Ethicon Women's Health and Urology, Somerville, NJ)
      balloon was introduced in the U.S. Soon thereafter, four other techniques were
      introduced, namely microwave (MEATM, Microsulis, Hampshire, UK), circulating hot
      water (HTATM, Boston Scientific, Boston, MA), cryo-ablation (HerOptionTM,
      CooperSurgical, Trumbull, CT), and bipolar radiofrequency (NovasureTM, Hologic,
      Bedford, MA). All of these techniques are done in an outpatient setting, often
      office-based, with little or no anesthesia, and success rates ranging from 50% to
      70% amenorrhea, and 80% to 95% patient satisfaction. Although there have been few
      head-to-head comparisons of various techniques, current data suggests that they
      are all relatively effective, quite safe, and well-tolerated. This article
      describes the history and development of various ablation technologies, and
      explores each technique in depth, including published data, indications, risks,
      and benefits. 

PMID- 24081841
TI  - Closure of midline laparotomies by means of small stitches: practical aspects of
      a new technique.
AB  - Randomized studies support the closure of midline incisions with a suture length
      to wound length ratio (SL:WL) of more than 4, accomplished with small tissue
      bites and short stitch intervals to decrease the risk of incisional hernia and
      wound infection. We investigated practical aspects of this technique possibly
      hampering the introduction of this technique. Patient data, operative variables
      and SL:WL ratio were collected at two hospitals: Sundsvall Hospital (SH) and
      Erasmus University Medical Center (EMC). A structured implementation of the
      technique had been performed at SH but not at EMC. Personnel were interviewed by
      questionnaire. At each hospital, 18 closures were analyzed. Closure time was
      significantly longer (p = 0.023) at SH (median 18 minutes, range: 9-59) than at
      EMC (median 13 minutes, range: 5-23). An SL:WL ratio of more than 4 was achieved
      in 8 of 18 cases at EMC and in all 18 cases at SH. We conclude that calculation
      of an SL:WL ratio is easily performed. Suturing with the small bite-short stitch
      interval technique of SH required 5 minutes extra, outweighing the morbidity of
      incisional hernia. Without a structured implementation to suture with an SL:WL
      ratio of more than 4, a lower ratio is often achieved. 

PMID- 24081842
TI  - Stepwise approach to laparoscopic hysterectomy: evaluation of technique and cost
      benefit.
AB  - This article examines factors associated with performing a laparoscopic
      hysterectomy in a stepwise fashion and addresses the technique and cost
      effectiveness of this procedure compared with abdominal hysterectomy. We review
      techniques of the laparoscopic hysterectomy as well difficulties that may be
      encountered throughout the procedure. The hysterectomy is profiled in a method
      that provides a reproducible system that allows surgeons to increase their
      surgical numbers and comfort level. When assessing cost-benefit analysis, the
      cost of hysterectomy is primarily influenced by the operative time, length of
      hospital stay, equipment, and complications. Robotic and laparoscopic
      hysterectomy had the highest mean hospital charges. The laparoscopic approach to
      hysterectomy provides better rates of recovery, length of stay, and hospital
      cost. The use of the stepwise approach to hysterectomy may allow surgeons to
      readily perform the procedure and also identify areas and techniques that need
      improvement. Regardless of age, body mass index (BMI), comorbities, and other
      nonclinical factors, the laparoscopic hysterectomy compared with abdominal
      hysterectomy and vaginal hysterectomy has been shown to be better for the
      patient's recovery and quality of life. 

PMID- 24081843
TI  - Spinous process fixation devices for instrumented spinal fusion.
AB  - Lumbar spinal fusion is a well-established surgical procedure for many spinal
      conditions. Posterior instrumentation may be added to provide immediate
      stabilization and improve fusion rates. Spinous process fixation, a type of
      posterior fixation, offers a less-invasive option to pedicle or facet screws with
      quantitative evidence of similar biomechanical stabilization; however, little has
      been published on the use of these devices. Further, there has been confusion
      about the use of spinous process fixation devices versus spinous process spacers.
      Spinous process fixation devices provide spine surgeons with another option for
      instrumented fusion, offering potential advantages for select patients.
      Biomechanical data suggest that relative to pedicle screws, modern spinous
      process fixation devices provide equivalent stability with reduced clinical risk
      and a less-invasive surgical procedure. These devices need to be distinguished
      from spacers, which are non-fixation devices. 

PMID- 24081844
TI  - Long-term results of femoral revision with the Wagner Self-Locking stem.
AB  - Femoral revision total hip arthroplasty may be a complex procedure due to
      extensive periprosthetic bone loss. Fluted, tapered stems provide secure axial
      and rotational stability in the distal femur. We retrospectively evaluated the
      long-term outcome of the cementless Wagner Self-Locking prosthesis (Sulzer
      Orthopedics Ltd, Winterthur, Switzerland). From 1992 to 1998, 68 consecutive
      femoral revisions were performed in 66 patients using the Wagner tapered stem.
      Twenty-five patients deceased for unrelated causes without additional surgery.
      The studied group consisted of 41 hips in 41 patients, 12 males and 29 females,
      aged from 29 to 80 years (mean 61 years). Thirty-five hips (85.4%) included
      severe deficiency of bone stock. A transfemoral approach was carried out in 32
      cases (78%). Bone grafting was never supplemented. Average follow-up was 13.9
      years (range 10.4 to 15.8 years). Clinical evaluation was performed using Harris
      Hip Score (HHS). Osseointegration of the stem and progression of periprosthetic
      bone remodelling were assessed radiographically. Five stems required rerevision
      because of deep infection (2), progressive subsidence (2) complicated by hip
      instability and head-neck disassembly, and old dislocation following acetabular
      component failure (1). Four hips (9.7%) dislocated, and 8 stems (19.5%) subsided
      significantly. Average HHS improved from 33 points preoperatively to 75 points at
      the latest follow-up examination (p < 0.001). Thirty-three of the 36 unrevised
      stems (91.7%) had radiographic evidence of bone ingrowth. A constant or decreased
      resorption of the femoral bone was detected in 34/36 patients (94.4%). The
      cumulative survival rates at 15.8 years with femoral revision for any reason and
      for stem failure as the end points were 92.0% and 96.6%, respectively. The
      current study documents the efficacy of distal fixation to the diaphysis in
      revision of bone-deficient femoral components, supporting the use of tapered,
      fluted stems. Higher-risk complications (dislocation, subsidence) should be
      minimized by the development of modular stems. 

PMID- 24081845
TI  - Assessing leg lengths intraoperatively in total hip arthroplasty: comparison of
      two methods.
AB  - Leg length discrepancy post total hip arthroplasty surgery is common. Unequal leg
      lengths after total hip arthroplasty is the single most common reason for
      litigation against orthopaedic surgeons. Different methods for leg length
      assessment are used intraoperatively by surgeons, but no one method is 100%
      reliable and reproducible. The aim of this study was to compare 2 methods of
      intraoperative leg length assessment. Leg length discrepancy of 5 mm or less was
      achieved in 72.5% (37/51) of patients using method 1 and in 67% (34/51) of
      patients using method 2. Both methods assessed produced a discrepancy of greater
      than 5 mm in about a quarter of the patients. The difference was not found to be
      statistically significant (p < 0.05). Assessment of leg lengths intraoperatively
      is challenging even for experienced surgeons. The leg lengths may be better
      restored if more than one method of assessment is used during surgery. 

PMID- 24081846
TI  - Outcomes and complications following spinous process fixation: a single-center
      analysis of 192 cases.
AB  - Spinous process fixation (SPF) is presented as less invasive than pedicle screws.
      There has been little quantitative data to support this assertion, and "minimally
      invasive" has not been well defined in spine surgery. Length of stay (LOS) and
      blood loss (BL) were chosen as surrogate measures of "minimally invasive." A
      chart review was conducted on 192 lumbar fusion patients (374 levels). A backward
      selection multiple-linear-regression was performed to determine what variables
      contribute to LOS and estimated blood loss (EBL). A logistic regression
      controlling for age and number of levels on complication rates was also
      performed. Number of levels with supplementary screw fixation (SSF) was
      significantly associated with LOS (p = 0.003). Controlling for number of surgical
      levels, LOS increased by 0.30 days (95% CI: 0.02-0.58) for each level with SSF.
      For each additional level including SSF, BL increases by 25.31 cc (95% CI: 3.50
      47.12, p = 0.023). Interbody fusion increases blood loss by 68.16 cc (95% CI:
      17.18-119.13, p = .009). For each additional level with SSF, odds of
      perioperative complications increase by OR = 2.34 (95% CI: 1.35-4.05). Long-term
      complications were not affected by instrumentation. LOS and BL are increased in
      patients with SSF vs. SPF only. Odds of perioperative complications are increased
      in patients with SSF relative to those treated with SPF alone. 

PMID- 24081847
TI  - Gastric plication: how to decrease the size of the stomach without transection.
AB  - Gastric plication is an emerging bariatric procedure with the potential for
      providing safe and significant weight loss and improvement of metabolic
      parameters without resection, bypass, or implantable device. Laparoscopic
      plication consists of infolding the greater gastric curvature to reduce stomach
      volume using running sutures. As a new procedure in bariatric/metabolic surgery
      very few clinical studies are available. Herein we present technical notes about
      and evidence from literature. 

PMID- 24081848
TI  - New advances in compression therapy for venous leg ulcers.
AB  - Leg ulceration, often caused by venous stasis, arterial insufficiency, or both,
      is a common chronic health condition often associated with a prolonged healing
      trajectory and frequent recurrence. It is estimated that approximately 1.5 to 3.0
      per 1,000 adults have active leg ulcers, and the prevalence continues to increase
      due to an aging population. Management of chronic edema using compression is
      crucial to promote healing of venous leg ulcers. The principle of compression
      therapy is simple, involving the use of external pressure in the forms of
      bandages or wraps to move the fluid from the interstitial space back into the
      intravascular compartment and prevent reflux. This article synthesizes and
      appraises the evidence for various types of compression therapies. It also
      addresses best practice recommendations for the management of leg ulcers when
      arterial circulation is considered suboptimal. 

PMID- 24081849
TI  - Sonographically guided hysteroscopic myomectomy (SGHM): minimizing the risks and
      maximizing efficiency.
AB  - Hysteroscopic myomectomy (HM), first described by Neuwirth and Amin in 1976,1 is
      an important technique in the management of selected women presenting with
      infertility, abnormal uterine bleeding (AUB), or both. The complications of HM
      include excessive bleeding, uterine perforation, prolonged operative times, and
      excessive intravasation of distention media. The author describes his technique
      of sonographically guided hysteroscopic myomectomy (SGHM). SGHM allows one to
      continuously monitor the progress of resectoscopic surgery while minimizing the
      risk of uterine perforation and permitting one to incorporate non-resectoscopic
      morcellation. The combination of both resectoscopic and non-resectoscopic
      techniques enable one to safely and efficiently remove submucous leiomyomas
      without the risk of excessive fluid absorption. 

PMID- 24081850
TI  - Use of the ENSEAL(r) G2 tissue sealer in gynecologic surgery.
AB  - Minimally invasive surgery (MIS) has become the standard of care for a variety of
      surgical conditions, and reliable vessel sealing and precise cutting are
      essential. A variety of tissue-sealing devices have been used successfully to
      decrease operating time and control bleeding during hysterectomy and other MIS
      gynecologic procedures. One development involves the next generation of advanced
      bipolar devices by ETHICON (Ethicon Endo-Surgery Inc., Cincinnati, OH), called
      ENSEAL(r) G2 Tissue Sealers. Tip improvements to the ENSEAL(r) have included
      stronger jaws and a welded positive electrode in the stationary jaw, thus
      enabling the new ENSEAL(r) G2 Tissue Sealer to provide reliable vessel sealing
      and precise cutting all in the same instrument. The patented I-BLADE(r) forces
      the jaws of the device together as it advances, resulting in high, uniform
      compression along the entire length of the jaws. The temperature-regulating
      Positive Temperature Coefficient (PTC) material in the jaws is designed to
      minimize sticking, and the offset electrode configuration is designed to minimize
      thermal spread. The ergonomics provided by the ENSEAL(r) G2 Tissue Sealer offer
      significant improvement over previous devices and may make this a much more cost
      effective choice for benign gynecologic procedures. 

PMID- 24081851
TI  - Retrospective comparison of Traditional vs. LigaSure impact dissection during
      pancreatoduodenectomy: how to save money by using an expensive device.
AB  - Pancreatoduodenectomy is an exceptional procedure that requires an extensive
      dissection of the supramesocolic region extended to the first jejunal limb.
      Lymphadenectomy, required for cancer, increases the dissection surface. The
      extensive preparation of the area is traditionally conducted with bipolar
      ormonopolar instruments, while clips, ligatures, and sutures are used for
      haemostasis. LigaSureTM vessel sealing(LSVS; Valleylab, Boulder, CO) is a
      technology that obtains vessel closure by using the body's own collagen and
      elastin to create a permanent fusion zone. This is obtained by a combination of
      forceps pressure and radio frequency. This effect has been improved by the
      introduction of the Force TriadTM (Valleylab, Boulder,CO) energy platform,
      controlled by TissueFectTM (Valleylab, Boulder, CO) sensing technology. With this
      device, the surgeon is able to fuse vessels up to 7 mm, lymphatics, tissue
      bundles, and pulmonary vasculature in a fast-seal cycle of almost 4 seconds. In
      our daily practice of open surgery we observe a rapid improvement of abdominal
      drainage output with a drastic reduction of protein loss. Its practical
      significance is, in our opinion, that we obtain a rapid recovery of normal serum
      protein levels with a low number of blood/plasmasac transfusions and a real
      improvement of anastomosis healing. Moreover, the efficacy and the speed of work
      of the device allow us to reduce the operating time significantly but safely. We
      performed a retrospective analysis of the data of 20 pancreatic resections
      conducted both with traditional dissection and with the Liga-Sure Impact device
      with Force Triad platform in order to verify whether observed data were real. Our
      clinical results show that the use of the LigaSure Impact device with Force Triad
      energy platform is really useful in open surgery to save operating time, number
      of postoperative days, and hemoderivate administration.

PMID- 24081852
TI  - The benefits of using barbed sutures with automated suturing devices in
      gynecologic endoscopic surgeries.
AB  - Laparoscopic suturing and knot tying are some of the most difficult surgical
      skills to acquire, and are often times regarded as a rate-limiting step in the
      performance of advanced gynecologic endoscopic procedures. Automated suturing
      devices can significantly decrease the steep learning curve of this task but
      still require laparoscopic knot tying. Barbed sutures offer several advantages
      including rapid, consistent wound closure with even distribution of tension
      across the wound, the suture holds tension on its own, the need for knot tying
      with associated issues related to suture tensile strength and knot security is
      eliminated, and suturing time is decreased. Use of a barbed suture with an
      automated suturing device can offer many advantages to both the novice and the
      experienced surgeon, including increased efficiency, more uniform wound closure,
      and the ability to perform a laparoscopic continuous running stitch without the
      need for intracorporeal knot tying.

PMID- 24081853
TI  - Fourth-generation endovascular stent-graft: the concept of laminar flow.
AB  - The stent graft is a noncompliant system inserted in a semi-compliant structure.
      This generates a mismatch. The media also shows a composite movement and is
      oriented 45 degrees  resulting in an arterial spiral movement that contributes to
      maintaining the clockwise orientation of laminar flow with an 80 degrees 
      deflection. Our multilayer stent is constituted by a single Nitinol thread,
      worked on 3 surfaces in order to realize a proper exoskeleton that reproduces the
      architecture of the tunica media, in particular its flexo-torsional forces, thus
      restoring the energy transmission and the match between the wall and the blood
      flow. A first in vivo implantation was performed by using an experimental pig
      model in our veterinary department. The pig underwent general anesthesia and the
      right femoral artery was surgically exposed in order to accommodate a 12F long
      introducer sheath. Under fluoroscopy three multilayer stents were consecutively
      implanted from the aortic isthmus to the iliac bifurcation in an overlap fashion.
      All the intercostal artery and visceral branches were covered by the overlapped
      stents. The final control angiography revealed an optimal sealing of the
      implanted stent with an evident flexotorsional oscillatory movement, which
      follows the conical architecture of the thoracic aorta and the complete patency
      of all the branches that arise from the aorta. After two months, the multilayer
      showed a normal endothelialization process with an optimal adhesion to the aortic
      wall both proximally and distally without provoking any inflammatory response or
      thickness wall alterations. The perfect and homogenous endothelialization
      preserved the patency of all the collateral branches arising from the treated
      aorta, in particular all the intercostal arteries, celiac trunk, and renal
      arteries. The disease of the aorta essentially concerns the tunica media as it
      causes disruption of the media components. This exoskeleton works like a neo
      tunica media, is perfectly endothelialized, and seems to optimally transmit the
      flexotorsional forces, restoring the match between wall and flow that represents
      the primary condition for laminar flow and branch perfusion.

PMID- 24081854
TI  - Dissonant role perception and paradoxical adjustments: an exploratory study on
      Medical Residents' collaboration with Senior Doctors and Head Nurses.
AB  - A good collaboration between health professionals is considered to have benefits
      for patients, healthcare staff, and organizations. Nevertheless, effective
      interprofessional collaboration is difficult to achieve. This is particularly
      true for collaboration between Medical Residents (MRs) and the immediate
      colleagues they interact with, as Senior Doctors (SDs) and Head Nurses (HNs).
      Role understanding is one of the factors that may explain difficulties in
      interprofessional collaboration. Based on this hypothesis, this paper focuses on
      MRs' role, devoting particular attention to differences in role perception
      between MRs, SDs, and HNs, and to their consequences for interprofessional
      collaboration. An exploratory qualitative study inspired by Grounded Theory was
      conducted in April 2009 in a small peripheral and non-university hospital in
      Switzerland. Data came from two focus groups with MRs (13), one with SDs (8), and
      one with HNs (7), and were analyzed using the constant comparative method.
      Findings show that the expected and the enacted role of MR are perceived
      differently by SDs, HNs and MRs themselves. To face the inconsistencies within
      MR's role, the three professional groups develop some adjustments that eventually
      prove to be paradoxical: on one side, they make collaboration possible and
      preserve the functioning of the ward, while on the other side they lead to mutual
      misunderstanding and discontent. These findings suggest that there is an urgent
      need of defining the role of MRs, of delimiting its boundaries and thereby
      distinguishing it from other health workers, and eventually of promoting a shared
      representation of it. 

PMID- 24081855
TI  - Lipid mediators of inflammation in obesity-related glomerulopathy.
AB  - The interplay between chronic kidney disease (CKD) and obesity represents the
      convergence of two of the most common contemporary clinical issues, and is of
      particular interest and significance in the context of the burden presented by
      each at present, and the dismal projections associated with both of these
      conditions for the future. That obesity leads to CKD through its association with
      other risks, such as hypertension, type 2 diabetes mellitus and atherosclerosis,
      is well established; however, it is likely that obesity itself is an independent
      risk factor for the development of CKD. The aetiology of this obesity-related
      glomerulopathy (ORG) is not clear, but it appears to be strongly influenced by
      chronic inflammation, manifest as a disturbance of the balance between pro
      inflammatory and pro-resolving lipid mediators, adipokines and mononuclear cells.
      This review examines the association between obesity and CKD, the role of
      inflammation therein, and the potential for pro-resolving lipid mediators to
      restore homoeostasis and offer therapeutic potential in ORG. 

PMID- 24081856
TI  - Beyond C4d: the ultrastructural appearances of endothelium in ABO-incompatible
      renal allografts.
AB  - BACKGROUND: ABO incompatibility is no longer a barrier in kidney transplantation.
      C4d is frequently positive in ABO-incompatible (iABO) biopsies without further
      signs of microcirculation injury. This phenomenon is assumed to represent graft
      accommodation. However, ultrastructural examination of glomerular and peritubular
      capillary endothelium might reveal subtle endothelial damage. METHODS: We studied
      the ultrastructural appearance of the endothelium in 67 biopsies from 21 patients
      with iABO allografts and compared it with 20 patients (29 biopsies) with ABO
      compatible (cABO) grafts with C4d positivity and 25 ABO-compatible control
      patients (25 biopsies) without serological or histological evidence of humoral
      rejection (C4d negative). Ten ultrastructural parameters indicative of chronic
      and acute glomerular and peritubular capillary damage in transmission electron
      microscopy (TEM) were semi-quantitatively graded and expressed in a sum score.
      Clinico-pathological data were compared as well as graft function at the time of
      biopsy and follow-up. RESULTS: Ultrastructural parameters did not significantly
      differ between iABO and controls. In contrast, C4d-positive cABO had the highest
      TEM sum score (P = 0.001 versus iABO, P = 0.002 versus controls). The sum score
      did not differ between C4d-positive and C4d-negative iABO but did differ between
      patients with and without anti-HLA donor-specific antibodies (DSA). Graft
      function in iABO at the time of biopsy and at follow-up was similar to controls.
      CONCLUSIONS: Our ultrastructural observations support the concept of endothelial
      accommodation in iABO renal transplants. C4d positivity in the ABO-incompatible
      situation does not indicate injurious activation of the complement cascade and
      does not seem to impact on the graft function, in contrast to C4d deposition in
      cABO with antibody-mediated rejection.

PMID- 24081858
TI  - Convective therapies versus low-flux hemodialysis for chronic kidney failure: a
      meta-analysis of randomized controlled trials.
AB  - BACKGROUND: Although convective therapies have gained popularity for the optimal
      removal of uremic solutes, their benefits and potential risks have not been fully
      elucidated. We conducted a meta-analysis of all randomized controlled trials
      comparing convective therapies with low-flux hemodialysis in patients with
      chronic kidney failure. METHODS: We performed a literature search using MEDLINE
      (inception-December 2012), Cochrane Central Register of Controlled Trials,
      ClinicalTrials.gov, scientific abstracts from meetings and bibliographies of
      retrieved articles. Randomized controlled trials comparing the effect of
      convective therapies including high-flux hemodialysis, hemofiltration or
      hemodiafiltration versus low-flux hemodialysis were included. Random-effects
      model meta-analyses were used to examine continuous and binary outcomes. RESULTS:
      Sixty-five (29 crossover and 36 parallel-arm) trials were identified (n = 12
      182). Convective therapies resulted in a decrease in all-cause mortality
      [relative risk (RR) 0.88; 95% confidence interval (CI) 0.76, 1.02, P = 0.09],
      cardiovascular mortality (RR 0.84; 95% CI 0.71, 0.98, P = 0.03), all-cause
      hospitalization (RR 0.91; 95% CI 0.82, 1.01; P = 0.08) and therapy-related
      hypotension (RR 0.55, 95% CI 0.35, 0.87, P = 0.01). Convective therapies also
      resulted in an increase in the clearance of several low-molecular-weight (urea,
      creatinine and phosphate), middle-sized (beta-2 microglobulin and leptin) and
      protein-bound (homocysteine, advanced glycation end-products and pentosidine)
      solutes and a decrease in inflammatory markers (interleukin-6). There was no
      impact of convective therapies on cardiac morphological and functional
      parameters, and blood pressure and anemia parameters. CONCLUSIONS: Although
      convective therapies are associated with improved clearance of uremic solutes,
      the potential long-term benefits of specific convective modalities require
      further study.

PMID- 24081857
TI  - Paracrine effects of transplanted mesothelial cells isolated from temperature
      sensitive SV40 large T-antigen gene transgenic rats during peritoneal repair.
AB  - BACKGROUND: The prevention and restoration of peritoneal damage is a critical
      mission in peritoneal dialysis (PD). Transplantation of mesothelial cells has
      been suggested to suppress peritoneal injury during PD. Few studies have examined
      the efficacy and safety of cell transplantation. We evaluated the paracrine
      effects of mesothelial transplantation during peritoneal repair using
      immortalized temperature-sensitive mesothelial cells (TSMCs) in chlorhexidine
      gluconate (CG)-induced peritoneal fibrosis rats. METHODS: Continuous-infusion
      pumps containing 8% CG were placed into the abdominal cavity for 21 days. After
      the removal of the pumps, the TSMCs were injected into the peritoneal cavity at
      Day 22 (Tx-1 group) or 29 (Tx-2 group). Morphological findings and mRNA
      expressions of regeneration-related factors were examined at Days 22, 29 and 35.
      RESULTS: Peritoneal thickness was aggravated in the Tx-1 group. Levels of
      transforming growth factor (TGF)-beta, vascular endothelial growth factor (VEGF)
      and matrix metalloproteinase-2 mRNA in the Tx-1 group at Day 35 were comparable
      with those at Day 22. The levels of Snail, B-Raf and ERK-1, markers of epithelial
      to mesenchymal transition and of the RAS/MAPK pathway in the Tx-1 group, were
      significantly higher than those in the Tx-2 group. TGF-beta and VEGF were
      produced from the transplanted mesothelial cells and the surrounding cells in the
      Tx-1 group. CONCLUSION: It appears that the paracrine effect of transplanted
      mesothelial cells during peritoneal repair is associated with its surrounding
      condition. It is important to determine the most appropriate time for developing
      peritoneal repair through mesothelial transplantation.

PMID- 24081859
TI  - Longitudinal changes in body mass index following renal transplantation in UK
      children.
AB  - BACKGROUND: Childhood obesity is a significant health problem in the UK. To date,
      there is little known about the pattern of change in body mass index (BMI)
      following renal transplantation in UK paediatric patients. Our objectives in this
      study were to (i) describe trends in BMI seen in UK patients undergoing renal
      transplantation in the short and medium term and (ii) identify risk factors
      predisposing children to excessive weight gain following transplantation.
      METHODS: A retrospective case note review was performed across 12 of 13
      paediatric nephrology centres in the UK, with BMI measurements recorded pre
      transplantation and for 4 years thereafter. BMI% was used to assess changes in
      adiposity over time. International Obesity Taskforce definitions of overweight
      and obesity were used to identify the prevalence of excess weight pre- and post
      renal transplantation. RESULTS: A total of 159 patients (113 boys) under the age
      of 18 with a functioning kidney transplant were included. Fifty-six patients
      (35.2%) were under the age of 5 at transplantation. Pre-transplantation, 31.4% of
      patients were classified as overweight or obese, which increased to 52.8% by the
      end of follow-up. The majority of patients experienced rapid increases in BMI%
      over the initial four months post-transplantation, which were sustained for the
      remainder of the follow-up period. The major risk factor for being overweight or
      obese at the end of follow-up was having excessive weight pre-transplantation.
      Four years following transplantation, the prevalence rate of overweight and
      obesity was much higher in our study cohort than the normal UK childhood
      population. CONCLUSIONS: The prevalence of patients classified as overweight or
      obese in the UK paediatric renal cohort is high pre-transplantation and rises
      subsequently. Those at risk can be identified by an unhealthy BMI pre
      transplantation and will require timely intervention with close monitoring in the
      subsequent post-transplantation period.

PMID- 24081860
TI  - Collapsing glomerulopathy superimposed on diabetic nephropathy: insights into
      etiology of an under-recognized, severe pattern of glomerular injury.
AB  - BACKGROUND: Collapsing glomerulopathy (CG) represents severe podocyte injury with
      massive proteinuria, rapid progression and relative resistance to therapy. It is
      associated with multiple etiologies, including obliterative arteriopathy in
      transplants. However, its association with diabetic nephropathy (DN) has not been
      reported. METHODS: Renal biopsies performed in diabetic patients for either
      increasing proteinuria or deteriorating renal function, or both, were
      retrospectively reviewed. The clinicopathologic features and immunohistochemical
      staining of podocytes were analyzed. RESULTS: Of 534 patients with DN, 26 human
      immunodeficiency virus (HIV)-negative patients were found to have CG superimposed
      on DN (5% DN cases). At the time of biopsy, their mean serum creatinine was 3.8
      mg/dL and proteinuria was 9.8 g/24 h. Renal biopsy showed CG in 2-30% (mean 16%
      of glomeruli), with segmental (2%) and global (33%) glomerulosclerosis. DN
      classification was Class IV-12, III-8, IIb-4 and IIa-2. Vascular sclerosis was
      moderate (44%) and severe (56%). Extensive arteriolar hyalinosis with >50%
      luminal stenosis was seen in 85% of cases. Markers of podocyte differentiation
      were lost, consistent with other types of CG. Cytokeratin was focally positive in
      70% and VEGF overexpressed in 43%. Follow-up on 17 patients: 13 developed end
      stage renal disease (ESRD) in 7 months from the time of biopsy. The development
      to ESRD in these patients was more rapid than diabetic controls without CG
      (P=0.005). The remaining four, 5-24 months follow-up, had an increase in
      creatinine with stable proteinuria. CONCLUSIONS: CG contributes to an increased
      level or new onset of proteinuria in DN which may be intractable. CG in DN with
      advanced vascular hyalinosis is presumably due to ischemic podocyte injury and is
      of prognostic significance.

PMID- 24081861
TI  - Japanese Dent disease has a wider clinical spectrum than Dent disease in
      Europe/USA: genetic and clinical studies of 86 unrelated patients with low
      molecular-weight proteinuria.
AB  - Dent disease is an X-linked disorder characterized by low-molecular-weight (LMW)
      proteinuria, hypercalciuria, nephrocalcinosis, urolithiasis and renal
      dysfunction. Dent disease is caused by mutations in at least two genes, i.e.
      CLCN5 and OCRL1, and its genetic background and phenotypes are common among
      European countries and the USA. However, only few studies on Dent disease in
      Japan, which was originally called 'low-molecular-weight proteinuric disease',
      have been reported thus far. In this study, we analysed genetic background and
      clinical phenotype and laboratory data of 86 unrelated Japanese Dent disease
      patients. The results demonstrated that the genetic basis of Japanese Dent
      disease was nearly identical to those of Dent disease in other countries. Of 86
      unrelated Japanese Dent patients, 61 possessed mutations in CLCN5 (Dent-1), of
      which 27 were novel mutations; 11 showed mutations in OCRL1 (Dent-2), six of
      which were novel, and the remaining 14 patients showed no mutations in CLCN5 or
      OCRL1 (Dent-NI). Despite the similarity in genetic background, hypercalciuria was
      detected in only 51%, rickets in 2% and nephrocalcinosis in 35%. Although the
      patients were relatively young, six patients (8%) showed apparent renal
      dysfunction. Japanese Dent disease has a wider clinical spectrum than Dent
      disease in Europe and the USA. 

PMID- 24081862
TI  - Definitions of progression in chronic kidney disease--predictors and relationship
      to renal replacement therapy in a population cohort with a 6 year follow-up.
AB  - BACKGROUND: Chronic kidney disease (CKD) is common, important and associated with
      increased healthcare needs due to CKD progression. Definitions of renal disease
      progression are multiple, and not always comparable. A measure of 'progression'
      directly comparable with renal replacement therapy (RRT) initiation would
      identify 'progressors' in research and for healthcare planning. METHODS: The
      Grampian Laboratory Outcomes Morbidity and Mortality Study (GLOMMS-I) is a
      community cohort with CKD from 2003, followed up to June 2009 for (i) RRT
      initiation and (ii) 'progression': sustained reduction in estimated glomerular
      filtration rate (eGFR) by 15 mL/min/1.73 m2 (equivalent to CKD stage change), or
      to <10 mL/min/1.73 m2, whichever occurs first. Predictors were baseline
      demographics and comorbidity. The use of the Kidney Disease: Improving Global
      Outcomes-2012 progression definition was also explored. RESULTS: Two thousand two
      hundred and eighty-nine and 1044 had Stage 3 and 4 CKD, 44% were males. Overall,
      RRT initiation and progression rates were 0.97 and 3.50 per 100 patient-years
      (py). Females had significantly lower progression and RRT initiation rates. The
      progression rate was not dependent on CKD stage [incidence rate ratio (IRR) for
      Stage 4 (versus Stage 3) 0.9 (95% CI 0.8-1.2)], whereas the RRT initiation rate
      was [IRR 5.6 (95% CI 3.8-8.2)]. Increased proteinuria was associated with both
      greater RRT initiation and progression rates. CONCLUSIONS: Progression and RRT
      initiation rate ratios allow comparison of predictors of these outcomes. Higher
      rates of both in males suggest that greater RRT initiation rate is biological
      rather than due to preferential treatment. Similar progression but very different
      RRT initiation rates in Stage 3 and 4 CKD suggests that CKD stage effect on RRT
      initiation is a function of endpoint proximity rather than faster renal function
      deterioration.

PMID- 24081863
TI  - Prevalence and severity of oral disease in adults with chronic kidney disease: a
      systematic review of observational studies.
AB  - BACKGROUND: Oral disease may be increased in people with chronic kidney disease
      (CKD) and, due to associations with inflammation and malnutrition, represents a
      potential modifiable risk factor for cardiovascular disease and mortality. We
      summarized the prevalence of oral disease in adults with CKD and explored any
      association between oral disease and mortality. METHODS: We used systematic
      review of observational studies evaluating oral health in adults with CKD
      identified in MEDLINE (through September 2012) without language restriction. We
      summarized prevalence and associations with all-cause and cardiovascular
      mortality using random-effects meta-analysis. We explored for sources of
      heterogeneity between studies using meta-regression. RESULTS: Eighty-eight
      studies in 125 populations comprising 11 340 adults were eligible. Edentulism
      affected one in five adults with CKD Stage 5D (dialysis) {20.6% [95% confidence
      interval (CI), 16.4-25.6]}. Periodontitis was more common in CKD Stage 5D [56.8%
      (CI, 39.3-72.8)] than less severe CKD [31.6% (CI, 19.0-47.6)], although data
      linking periodontitis with premature death were scant. One-quarter of patients
      with CKD Stage 5D reported never brushing their teeth [25.6% (CI, 10.2-51.1)] and
      a minority used dental floss [11.4% (CI, 6.2-19.8)]; oral pain was reported by
      one-sixth [18.7% (CI, 8.8-35.4)], while half of patients experienced a dry mouth
      [48.4% (CI, 37.5-59.5)]. Data for kidney transplant recipients and CKD Stages 1-5
      were limited. CONCLUSIONS: Oral disease is common in adults with CKD, potentially
      reflects low use of preventative dental services, and may be an important
      determinant of health in this clinical setting.

PMID- 24081864
TI  - Preoperative angiotensin-converting enzyme inhibitors and angiotensin receptor
      blocker use and acute kidney injury in patients undergoing cardiac surgery.
AB  - BACKGROUND: Using either an angiotensin-converting enzyme inhibitor (ACEi) or an
      angiotensin receptor blocker (ARB) the morning of surgery may lead to
      'functional' postoperative acute kidney injury (AKI), measured by an abrupt
      increase in serum creatinine. Whether the same is true for 'structural' AKI,
      measured with new urinary biomarkers, is unknown. METHODS: The TRIBE-AKI study
      was a prospective cohort study of 1594 adults undergoing cardiac surgery at six
      hospitals between July 2007 and December 2010. We classified the degree of
      exposure to ACEi/ARB into three categories: 'none' (no exposure prior to
      surgery), 'held' (on chronic ACEi/ARB but held on the morning of surgery) or
      'continued' (on chronic ACEi/ARB and taken the morning of surgery). The co
      primary outcomes were 'functional' AKI based upon changes in pre- to
      postoperative serum creatinine, and 'structural AKI', based upon peak
      postoperative levels of four urinary biomarkers of kidney injury. RESULTS: Across
      the three levels (none, held and continued) of ACEi/ARB exposure there was a
      graded increase in functional AKI, as defined by AKI stage 1 or worse; (31, 34
      and 42%, P for trend 0.03) and by percentage change in serum creatinine from pre-
      to postoperative (25, 26 and 30%, P for trend 0.03). In contrast, there were no
      differences in structural AKI across the strata of ACEi/ARB exposure, as assessed
      by four structural AKI biomarkers (neutrophil gelatinase-associated lipocalin,
      kidney injury molecule-1, interleukin-18 or liver-fatty acid-binding protein).
      CONCLUSIONS: Preoperative ACEi/ARB usage was associated with functional but not
      structural acute kidney injury. As AKI from ACEi/ARB in this setting is unclear,
      interventional studies testing different strategies of perioperative ACEi/ARB use
      are warranted.

PMID- 24081866
TI  - European Renal Best Practice (ERBP) Guideline development methodology: towards
      the best possible guidelines.
AB  - The prime mission of European Renal Best Practice (ERBP) is to improve the
      outcome of patients with kidney disease in a sustainable way through enhancing
      the availability of the knowledge on the management of these patients in a format
      that stimulates its use in clinical practice in Europe. A key activity is to
      produce clinical practice guidelines to help clinicians make the healthcare
      decisions they face. To further improve the quality and validity of its clinical
      practice guidelines, ERBP has revised its guideline development process. The
      present document outlines the principles of ERBP's 10-step approach. Important
      features include standard procedures for selecting topics, for assembling the
      guideline development group, for choosing and formulating questions, for finding,
      appraising and summarizing the evidence, for generating recommendations, for
      preparing reports and organizing peer review. ERBP has adopted the Grading of
      Recommendations Assessment, Development and Evaluation system for rating the
      quality of the evidence and strength of recommendations and has addressed
      implementation in the development process by integrating the GuideLine
      Implementability Appraisal tool. Ultimately, it is anticipated that these changes
      will not only further improve the quality of the guideline development process,
      but also enhance the quality of care and improve outcomes of patients with kidney
      disease across Europe. 

PMID- 24081865
TI  - Clinical and immunological implications of increase in CD208+ dendritic cells in
      tonsils of patients with immunoglobulin A nephropathy.
AB  - BACKGROUND: The therapeutic effect of tonsillectomy for immunoglobulin A
      nephropathy (IgAN) has been widely recognized, but the mechanism by which
      tonsillar immunity leads to glomerulonephritis has been unclear. We investigated
      subtypes and localization of dendritic cells (DCs) in tonsils and looked for
      relationships between the tonsillar DCs and the clinical features and renal
      histological changes of patients with IgAN. METHODS: We examined tonsils from 33
      IgAN patients, using as control tonsillar specimens from subjects without
      glomerulonephritis. Five distinct markers of DCs (CD303, CD1c, CD209, CD208 and
      CD1a) were analyzed by immunohistochemistry and flow cytometry. The mRNA levels
      of these DC markers were evaluated using real-time polymerase chain reaction. The
      clinical data and histological results obtained evaluating renal biopsy tissues
      were statistically compared with immunological data. RESULTS: Of the five
      subtypes of DCs, CD208(+) DCs were significantly increased in the tonsils of IgAN
      patients compared with that of controls. Furthermore, the number of CD208(+) DCs
      in the tonsils was positively and linearly correlated with the proportion of
      crescentic glomeruli in renal biopsy tissues and with the urinary protein level.
      Only few CD208(+) cells, however, were found in the kidney biopsy specimens of
      IgAN patients. CONCLUSIONS: These observations suggest that increased CD208(+)
      DCs in tonsils may play a directive role in the pathogenesis of IgAN. The present
      results support the therapeutic significance of tonsillectomy for IgAN patients.

PMID- 24081867
TI  - Clinical implication of crescentic lesions in immunoglobulin A nephropathy.
AB  - BACKGROUND: To date, there has been much controversy about the role of crescentic
      lesion as a significant prognostic factor in immunoglobulin A nephropathy (IgAN).
      This study evaluated whether crescentic lesions predict adverse renal outcomes in
      IgAN patients. METHODS: A total of 430 patients with biopsy-proven IgAN between
      January 2000 and December 2009 were included. Histological variables of the
      Oxford classification (Oxford-MEST) and the presence of crescents were assessed.
      The primary endpoint was a 50% decline in estimated glomerular filtration rate.
      RESULTS: Of the 430 patients, 81 (18.8%) had a crescentic lesion. During a mean
      follow-up of 61 months, the primary outcome occurred in 19 (23.5%) patients with
      crescents compared with 40 (11.5%) patients without crescents (P=0.01). A Kaplan
      Meier plot showed that the 10-year renal survival rate was significantly lower in
      patients with crescents than patients without crescents (P=0.01). However, in a
      multivariable Cox analysis which included clinical factors and the Oxford-MEST,
      crescents were not significantly associated with an increased risk of developing
      the primary outcome [hazard ratio: 0.71, 95% confidence interval (CI) 0.36-1.41,
      P=0.33]. Furthermore, adding crescents to the Oxford-MEST did not improve the
      discriminative ability for the prediction of renal outcomes [c-statistic: 0.86
      (0.81-0.91) vs. 0.86 (0.80-0.91), P=0.21]. CONCLUSION: Crescentic lesion was not
      an independent prognostic factor, suggesting that crescents have limited value in
      predicting renal outcomes of IgAN.

PMID- 24081868
TI  - The impact of severe preeclampsia on maternal quality of life.
AB  - PURPOSE: Preeclampsia (PE) is a serious life event that can change women's
      psychological profile. The aim of this study was to evaluate the physical and
      mental health-related quality of life (HR-QoL) in women after PE and the impact
      of contributing factors. METHODS: Ninety-five women who had suffered from PE
      answered the Short-Form-12 Health Survey on general state of health. Comparison
      was made with the reference values and among the study cohorts, namely mild (14.7
      %), severe (74.7 %) and superimposed PE (10.5 %). Medical parameters were
      evaluated as additional factors, and age served as covariate. RESULTS: Quality of
      mental life was significantly worse in all patients (p < 0.01), especially in
      those after severe PE (p < 0.01) compared to the reference range. These women
      demonstrated significantly worse results than those affected by the mild form (p
      = 0.03). Women who had had superimposed PE were neither physically nor mentally
      impaired compared to the standard population values (p = 0.94 and p = 0.90,
      respectively). After controlling for medical parameters and age, differences
      remained statistically significant. Multiparous women scored significantly worse
      on the mental scale than primiparous (p = 0.02), and pregnant women scored
      significantly worse than non-pregnant women on the physical level (p = 0.04).
      CONCLUSIONS: This study shows that women who have suffered from severe PE are
      substantially reduced in their mental quality of life. An extensive medical care
      including HR-QoL parameters might improve pregnancy outcome.

PMID- 24081869
TI  - Longitudinal construct validity of the Health Utilities Indices Mark 2 and Mark 3
      in hip fracture.
AB  - PURPOSE: The objective of this study is to evaluate the longitudinal construct
      validity of the Health Utilities Index Mark 2 (HUI2) and Health Utilities Index
      Mark 3 (HUI3) using a convergent/divergent validity approach in patients
      recovering from hip fracture, with the Functional Independence Measure (FIM) as
      the comparator. METHODS: A total of 278 patients with a primary diagnosis of hip
      fracture were interviewed 3-5 days after surgery and then at 1 and 6 months using
      the HUI2, HUI3 and the FIM and a Likert-type rating of hip pain. A priori
      hypotheses were formulated. Convergent and divergent correlations between HUI2,
      HUI3 and FIM change scores for the baseline to 1-month and baseline to 6-month
      intervals were examined. RESULTS: Overall HUI2 detected continued gain in health
      related quality of life between 1 and 6 months after fracture, as the change
      increased from 0.20 to 0.29 units. The correlation between change in the overall
      HUI2 score and total FIM score was moderate (r = 0.50) over the 6-month interval,
      but larger than the observed correlation over the 1-month interval (r = 0.36).
      The correlation between change in overall HUI3 score and total FIM over the 1
      month interval was small (r = 0.32), and the correlation between change in
      overall HUI3 score and total FIM was moderate (r = 0.37) over the 6-month
      interval. All hypotheses for the divergent correlations were supported.
      CONCLUSIONS: Weaker correlations were reported for change over 1 month as
      compared to change over the 6 months after fracture. Findings supported the
      longitudinal construct validity of the overall HUI2 and HUI3 for the assessment
      of recovery following hip fracture, particularly for change over the 6 months
      following fracture.

PMID- 24081870
TI  - Validity, reliability and discriminative capacity of an electronic quality of
      life instrument (Pelican) for childhood asthma in the Netherlands.
AB  - PURPOSE: To assess psychometric properties of the Pelican instrument, an online
      Dutch self-administered Quality of Life instrument for childhood asthma for
      scientific and clinical use. METHODS: A cohort study was done in two asthma
      populations and healthy children. One asthma population had assessment at start,
      4 and 8 weeks. The other asthma population and healthy children had one
      assessment. All children were aged 6-12 years. Children completed the Pelican
      instrument, Paediatric Asthma Quality of Life Questionnaire, feeling thermometer
      and Childhood Asthma Control Test. Lung function and fraction exhaled nitric
      oxide were measured. Parents completed Functional Status II, Asthma Control
      Questionnaire, Childhood Asthma Control Test questionnaires and symptom diaries.
      We assessed interpretability, structural validity, internal consistency,
      reliability, construct and discriminative validity of the Pelican instrument.
      RESULTS: Eighty-five asthmatic (mean age 8.5 years) and 49 healthy children (mean
      age 8.4 years) participated. The Pelican instrument has 5 domains with 21 items
      after factor analysis. Internal consistency was 0.89 (CI 0.85-0.92), domain
      reliability showed Cronbach's alpha's from 0.64 to 0.76 and item-to-scale
      correlations from 0.61 to 0.81. Test-retest reliability was confirmed ICC = 0.88
      (CI 0.79-0.93). Construct validity was demonstrated by significant moderate
      correlations with other relevant asthma outcomes like PAQLQ (r = -0.59, p <
      0.01). Discriminative capacity between controlled or uncontrolled asthma (t =
      3.20, p < 0.01, Delta = 0.64) and asthma versus healthy subjects (t = 6.31, p <
      0.01, Delta = 0.94) was found. CONCLUSIONS: The psychometric properties of the
      Pelican instrument were acceptable in Dutch paediatric asthma patients between 6
      and 12 years old.

PMID- 24081871
TI  - Change in quality of life and predictors of change among patients with multiple
      sclerosis: a prospective cohort study.
AB  - PURPOSE: The aim of this study was to determine the changes in the health-related
      quality of life (HRQoL) and predictors of change among patients with multiple
      sclerosis (MS) at 3 and 6 years during the follow-up period. METHODS: A group of
      109 consecutive MS patients (McDonald's criteria) referred to the Clinic of
      Neurology, Belgrade, were enrolled in the study. At three time points during the
      study (baseline, and at 3 and 6 years during the follow-up period), the HRQoL
      (measured by MSQoL-54), Expanded Disability Status Scale, and Hamilton Rating
      Scale for Depression and Fatigue Severity Scale were assessed. RESULTS: During
      the study period, 93 patients provided both follow-up assessments. Statistically
      significant deterioration in the HRQoL at each subsequent time point was detected
      for all scales of the MSQoL-54 except for the pain and change in health scales. A
      higher level of education was a significant prognostic factor for a better HRQoL
      on the cognitive function scale throughout the entire period of observation,
      while marital status (single, including divorced and widowed) and increased age
      at the onset of MS had significant predictive values of poorer quality-of-life
      scores on the overall quality-of-life scale at 6-year follow-up. Higher levels of
      physical disability and depression at baseline were statistically significant
      prognostic markers for deterioration in HRQoL for the majority of MSQoL-54 scales
      during the entire follow-up period. CONCLUSIONS: Our study suggests that baseline
      demographic and clinical characteristics could be applied as prognostic markers
      of the HRQOL for patients diagnosed with MS.

PMID- 24081872
TI  - The mediating role of disability and social support in the association between
      low vision and depressive symptoms in older adults.
AB  - PURPOSE: Vision loss is highly prevalent in old age and has a substantial impact
      on different aspects of quality of life including depressive symptoms. Our
      objective was to examine the mediating role of disability and social support in
      the association between low vision and depressive symptoms. METHODS: Differences
      in disability, social support, and depressive symptoms between 148 persons with
      low vision and a reference population (N = 4,792) all >=57 years were compared.
      The association between low vision and depressive symptoms and the mediating role
      of disability and social support was examined by the means of regression.
      RESULTS: A significant effect of low vision on depressive symptoms was identified
      even after the adjustment for disability and social support (standardized beta
      0.053, P < 0.001). The association between low vision and symptoms of depression
      was partially mediated by disability, while social support was identified as a
      suppressor variable. Low vision, disability, and social support showed unique
      contributions to depressive symptoms. CONCLUSIONS: Prevention of disability and
      the increase in social support may help to reduce symptoms of depression in older
      adults with low vision. By taking such information into account in their
      intervention work, health professionals working in this area may improve their
      care quality.

PMID- 24081873
TI  - Assessing the performance of the EQ-VAS in the NHS PROMs programme.
AB  - OBJECTIVES: The study aims to increase knowledge about the performance of the
      EuroQol-visual analogue scales (EQ-VAS) in the UK NHS patient-reported outcome
      measures (PROMs) programme, which covers groin hernia, hip and knee replacement
      and varicose vein surgery, and make suggestions for improved collection, coding
      and analysis of data. METHODS: Four hundred scanned images of matched before-and
      after EQ-VAS PROMs responses were selected at random. These were classified
      according to the different ways in which they were completed. Patient-level PROMs
      programme data linked to Hospital Episode Statistics for all patients from April
      2009 to February 2011 were used to analyse the relationship between the EQ-VAS
      and the EQ-5D profile, index-weighted profile and condition-specific instruments.
      The linked PROMs and HES data comprise 331,951 anonymised patient records.
      RESULTS: A large majority (95 %) of EQ-VAS responses were completed in an
      unambiguous way, but only a minority (45 %) conformed strictly to the
      instructions given, posing challenges for data coding. The EQ-VAS data have a
      predictable and consistent relationship with the EQ-5D profile, although the
      correlations between the EQ-VAS and other measures of patient-reported health,
      both before and after surgery and in the change between them, are weak.
      CONCLUSIONS: EQ-VAS data might be improved by providing better guidance on
      collection and coding. It is argued that the observed differences in results from
      EQ-VAS and other measures of health reflect the fact that it measures a broader
      underlying construct of health, arguably providing a means of summarising overall
      health that is closer to the patient's perspective.

PMID- 24081874
TI  - Quality of life for parents of children with influenza-like illness: development
      and validation of Care-ILI-QoL.
AB  - PURPOSE: Influenza-like illnesses (ILI) cause paediatric morbidity and affect the
      quality of life (QoL) of children and their parents. We have developed a disease
      specific questionnaire (Care-ILI-QoL) to measure the QoL of caregivers of
      children with ILI. METHODS: The drafting of the Care-ILI-QoL questionnaire was
      based on a systematic review, a quantitative survey, qualitative interviews with
      parents, and meetings with paediatricians. Children aged 6-48 months recruited
      from childcare centres in Sydney, Australia, were followed up during the 2011
      influenza season. Care-ILI-QoL and SF-12v2 Acute Form were administered to the
      parent of a sick child 2 weeks after the onset of ILI, and again 2 weeks after
      the child had recovered. Exploratory factor analysis was conducted. Internal
      consistency, concurrent validity, discriminant validity, homogeneity of items,
      and responsiveness were tested. RESULTS: Out of the 125 children enrolled from 48
      childcare centres, 55 children had ILI (total 75 ILI episodes). Care-ILI-QoL was
      reduced from 25 to 16 items covering four factors: Daily Activities, Perceived
      Support, Social Life, and Emotions (Cronbach's alphas 0.90, 0.92, 0.78, and 0.72,
      respectively). Care-ILI-QoL has satisfactory concurrent and discriminant
      validity, good internal consistency, and excellent responsiveness. Total QoL and
      factor scores correlated well with SF-12v2 scores. Total QoL scores were
      significantly lower in parents who perceived their child as very/extremely sick,
      sacrificed 10 hours or more in work or recreation in caring for the child, or
      whose child had two or more general practitioner visits. Total QoL and factor
      scores were significantly higher after the child had recovered than when the
      child had ILI. CONCLUSIONS: Care-ILI-QoL is the first ILI-specific QoL instrument
      for parents and is demonstrated to be valid and reliable in a developed country
      setting where the child is affected by ILI. It has the potential to be applied in
      clinical and research settings to assist measurement of disease burden, as a
      needs assessment tool for resources or to inform policy changes.

PMID- 24081875
TI  - Validation of the Rhinoplasty Outcomes Evaluation (ROE) questionnaire adapted to
      Brazilian Portuguese.
AB  - PURPOSE: The aim of this study was to validate the Rhinoplasty Outcomes
      Evaluation (ROE) questionnaire adapted to the Brazilian Portuguese. METHOD: A
      prospective study was conducted with ROE administration to 56 patients submitted
      to rhinoplasty (preoperatively, and then 15-day and 90-day postoperatively) and
      100 volunteers without the need or desire of cosmetic or functional nasal
      surgery. Reliability (internal consistency and test-retest reproducibility),
      validity, responsiveness and clinical interpretability were assessed. RESULTS:
      Rhinoplasty patients' mean preoperative score was 7.14, 15 days post-op 17.73 and
      90 days post-op 20.50, while controls presented 17.94 points (p < 0.0001),
      showing the questionnaire's validity and responsiveness. Internal consistency was
      0.86. Inter- and intra-examiner test-retest reproducibility was 0.90 and 0.94,
      respectively. The effect size caused by the surgery was considered large (15 days
      post-op compared to the preoperative score: effect size = 3.22; 90 days post-op
      compared to preoperative score: effect size = 4.06). The minimally important
      difference was 8.67 points, so changes smaller than 9 points in ROE might not be
      perceived by the patient as an improvement or worsening. CONCLUSION: The
      Brazilian Portuguese version of ROE is a valid instrument to assess results in
      rhinoplasty patients.

PMID- 24081876
TI  - Computer-aided staging of lymphoma patients with FDG PET/CT imaging based on
      textural information.
AB  - We have designed a computer-aided diagnosis system to discriminate between
      hypermetabolic cancer lesions and hypermetabolic inflammatory or physiological
      but noncancerous processes in FDG PET/CT exams of lymphoma patients. Detection
      performance of the support vector machine (SVM) classifier was assessed based on
      feature sets including 105 positron emission tomography (PET) and Computed
      tomography (CT) characteristics derived from the clinical practice and from more
      sophisticated texture analysis. An original feature selection method based on
      combining different filter methods was proposed. The evaluation database
      consisted of 156 lymphomatous and 32 suspicious but nonlymphomatous regions of
      interest. Different types of training databases including either the PET and CT
      features or the PET features only, with or without feature selection, were
      evaluated to assess the added value of multimodality and texture information on
      classification performance. An optimization study was conducted for each
      classifier separately to select the best combination of parameters. Promising
      classification performance was achieved by the SVM classifier combined with the
      12 most discriminant PET and CT features with a value of the area under the
      receiver operating curve of 0.91. 

PMID- 24081877
TI  - In vitro recapitulation of the urea cycle using murine embryonic stem cell
      derived in vitro liver model.
AB  - Ammonia, a toxic metabolite, is converted to urea in hepatocytes via the urea
      cycle, a process necessary for cell/organismal survival. In liver, hepatocytes,
      polygonal and multipolar structures, have a few sides which face hepatic
      sinusoids and adjacent hepatocytes to form intercellular bile canaliculi
      connecting to the ductules. The critical nature of this three-dimensional
      environment should be related to the maintenance of hepatocyte function such as
      urea synthesis. Recently, we established an in vitro liver model derived from
      murine embryonic stem cells, IVL(mES), which included the hepatocyte layer and a
      surrounding sinusoid vascular-like network. The IVL(mES) culture, where the
      hepatocyte is polarized in a similar fashion to its in vivo counterpart, could
      successfully recapitulate in vivo results. L-Ornithine is an intermediate of the
      urea cycle, but supplemental L-ornithine does not activate the urea cycle in the
      apolar primary hepatocyte of monolayer culture. In the IVL(mES), supplemental L
      ornithine could activate the urea cycle, and also protect against
      ammonium/alcohol-induced hepatocyte death. While the IVL(mES) displays
      architectural and functional properties similar to the liver, primary hepatocyte
      of monolayer culture fail to model critical functional aspects of liver
      physiology. We propose that the IVL(mES) will represent a useful, humane
      alternative to animal studies for drug toxicity and mechanistic studies of liver
      injury. 

PMID- 24081878
TI  - Correlates of obstructive apnea duration.
AB  - PURPOSE: The duration of an obstructive apnea is dependent on gender, age, body
      position, and state. Termination of an obstructive respiratory event is
      attributed as the end result of an achieved specific negative inspiratory force,
      sufficient to result in cortical arousal. We used polysomnographic measures of
      tendency for arousal, hypothesizing that long apnea would be associated with a
      smaller tendency for arousal. METHODS: From a clinical sleep laboratory sample,
      140 subjects (82 men) with an obstructive apnea index >5 were selected. Subjects
      were split into those with long and short apnea by stratifying around median
      obstructive apnea duration. Those with long duration apnea were compared to short
      apnea for age, gender, apnea-hypopnea index (AHI), and a measure of tendency to
      arouse, respiratory event-related arousal to AHI ratio (RespArI:AHI). RESULTS:
      Obstructive apnea duration (mean +/- SD) was 20.7 +/- 5.6. Apnea duration trended
      toward being longer in men than women and was significantly longer in supine than
      nonsupine sleep (19.2 +/- 7.3 vs. 16.1 +/- 10; p = 0.001) and REM than NREM sleep
      (24.3 +/- 9.0 vs. 19.7 +/- 5.1; p < 0.001). Those with long compared with short
      apnea were significantly older; AHI was similar. RespArI:AHI was significantly
      higher for those with long compared with short apnea (0.58 +/- 0.24 and 0.43 +/-
      0.19; p < 0.0001). This difference was most apparent for women in whom
      RespArI:AHI for those with long and short apnea was 0.6 +/- 0.24 and 0.41 +/-
      0.17 (p = 0.001). For men, RespArI:AHI for those with long and short obstructive
      apnea was 0.56 +/- 0.24 and 0.44 +/- 0.2 (p = 0.02). CONCLUSIONS: Long
      obstructive apnea duration occurs to a greater degree in older individuals, in
      supine, and REM sleep. Women more than men with long apnea had a greater tendency
      toward arousal.

PMID- 24081879
TI  - Thrombospondin-1 induction in the diabetic myocardium stabilizes the cardiac
      matrix in addition to promoting vascular rarefaction through angiopoietin-2
      upregulation.
AB  - RATIONALE: Diabetes mellitus is associated with cardiac fibrosis. Matricellular
      proteins are induced in fibrotic conditions and modulate fibrogenic and
      angiogenic responses by regulating growth factor signaling. OBJECTIVE: Our aim
      was to test the hypothesis that the prototypical matricellular protein
      thrombospondin (TSP)-1, a potent angiostatic molecule and crucial activator of
      transforming growth factor-beta, may play a key role in remodeling of the
      diabetic heart. METHODS AND RESULTS: Obese diabetic db/db mice exhibited marked
      myocardial TSP-1 upregulation in the interstitial and perivascular space. To
      study the role of TSP-1 in remodeling of the diabetic heart, we generated and
      characterized db/db TSP-1(-/-) (dbTSP) mice. TSP-1 disruption did not
      significantly affect weight gain and metabolic function in db/db animals. When
      compared with db/db animals, dbTSP mice had increased left ventricular dilation
      associated with mild nonprogressive systolic dysfunction. Chamber dilation in
      dbTSP mice was associated with decreased myocardial collagen content and
      accentuated matrix metalloproteinase-2 and -9 activity. TSP-1 disruption did not
      affect inflammatory gene expression and activation of transforming growth factor
      beta/small mothers against decapendaplegic signaling in the db/db myocardium. In
      cardiac fibroblasts populating collagen pads, TSP-1 incorporation into the matrix
      did not activate transforming growth factor-beta responses, but inhibited leptin
      induced matrix metalloproteinase-2 activation. TSP-1 disruption abrogated age
      associated capillary rarefaction in db/db mice, attenuating myocardial
      upregulation of angiopoietin-2, a mediator that induces vascular regression. In
      vitro, TSP-1 stimulation increased macrophage, but not endothelial cell,
      angiopoietin-2 synthesis. CONCLUSIONS: TSP-1 upregulation in the diabetic heart
      prevents chamber dilation by exerting matrix-preserving actions on cardiac
      fibroblasts and mediates capillary rarefaction through effects that may involve
      angiopoietin-2 upregulation.

PMID- 24081880
TI  - Selective modulation of coupled ryanodine receptors during microdomain activation
      of calcium/calmodulin-dependent kinase II in the dyadic cleft.
AB  - RATIONALE: In ventricular myocytes of large mammals with low T-tubule density, a
      significant number of ryanodine receptors (RyRs) are not coupled to the
      sarcolemma; cardiac remodeling increases noncoupled RyRs. OBJECTIVE: Our aim was
      to test the hypothesis that coupled and noncoupled RyRs have distinct microdomain
      dependent modulation. METHODS AND RESULTS: We studied single myocytes from pig
      left ventricle. The T-tubule network was analyzed in 3-dimension (3D) to measure
      distance to membrane of release sites. The rising phase of the Ca(2+) transient
      was correlated with proximity to the membrane (confocal imaging, whole-cell
      voltage-clamp, K5fluo-4 as Ca(2+) indicator). Ca(2+) sparks after stimulation
      were thus identified as resulting from coupled or noncoupled RyRs. We used high
      frequency stimulation as a known activator of Ca(2+)/calmodulin-dependent kinase
      II. Spark frequency increased significantly more in coupled than in noncoupled
      RyRs. This specific modulation of coupled RyRs was abolished by the
      Ca(2+)/calmodulin-dependent kinase II blockers autocamtide-2-related inhibitory
      peptide and KN-93, but not by KN-92. Colocalization of Ca(2+)/calmodulin
      dependent kinase II and RyR was not detectably different for coupled and
      noncoupled sites, but the F-actin disruptor cytochalasin D prevented the specific
      modulation of coupled RyRs. NADPH oxidase 2 inhibition by diphenyleneiodonium or
      apocynin, or global reactive oxygen species scavenging, also prevented coupled
      RyR modulation. During stimulated Ca(2+) transients, frequency-dependent increase
      of the rate of Ca(2+) rise was seen in coupled RyR regions only and abolished by
      autocamtide-2-related inhibitory peptide. After myocardial infarction, selective
      modulation of coupled RyR was lost. CONCLUSIONS: Coupled RyRs have a distinct
      modulation by Ca(2+)/calmodulin-dependent kinase II and reactive oxygen species,
      dependent on an intact cytoskeleton and consistent with a local Ca(2+)/reactive
      oxygen species microdomain, and subject to modification with disease.

PMID- 24081882
TI  - TOPSIS-based consensus model for group decision-making with incomplete interval
      fuzzy preference relations.
AB  - Due to the vagueness of real-world environments and the subjective nature of
      human judgments, it is natural for experts to estimate their judgements by using
      incomplete interval fuzzy preference relations. In this paper, based on the
      technique for order preference by similarity to ideal solution method, we present
      a consensus model for group decision-making (GDM) with incomplete interval fuzzy
      preference relations. To do this, we first define a new consistency measure for
      incomplete interval fuzzy preference relations. Second, a goal programming model
      is proposed to estimate the missing interval preference values and it is guided
      by the consistency property. Third, an ideal interval fuzzy preference relation
      is constructed by using the induced ordered weighted averaging operator, where
      the associated weights of characterizing the operator are based on the defined
      consistency measure. Fourth, a similarity degree between complete interval fuzzy
      preference relations and the ideal one is defined. The similarity degree is
      related to the associated weights, and used to aggregate the experts' preference
      relations in such a way that more importance is given to ones with the higher
      similarity degree. Finally, a new algorithm is given to solve the GDM problem
      with incomplete interval fuzzy preference relations, which is further applied to
      partnership selection in formation of virtual enterprises. 

PMID- 24081881
TI  - Activation of NADPH oxidase 4 in the endoplasmic reticulum promotes cardiomyocyte
      autophagy and survival during energy stress through the protein kinase RNA
      activated-like endoplasmic reticulum kinase/eukaryotic initiation factor
      2alpha/activating transcription factor 4 pathway.
AB  - RATIONALE: Autophagy is an essential survival mechanism during energy stress in
      the heart. Oxidative stress is activated by energy stress, but its role in
      mediating autophagy is poorly understood. NADPH oxidase (Nox) 4 is an enzyme that
      generates reactive oxygen species (ROS) at intracellular membranes. Whether Nox4
      acts as a sensor of energy stress to mediate activation of autophagy is unknown.
      OBJECTIVE: We investigated whether Nox4 is involved in the regulation of
      autophagy and cell survival during energy stress in cardiomyocytes. METHODS AND
      RESULTS: Production of ROS in cardiomyocytes was increased during glucose
      deprivation (GD) in a Nox4-dependent manner. Protein levels and the ROS-producing
      activity of Nox4 were increased in the endoplasmic reticulum (ER), but not in
      mitochondria, in response to GD. Selective knockdown of Nox4, but not Nox2, or
      selective reduction of ROS in the ER with ER-targeted catalase, but not
      mitochondria-targeted perioxiredoxin 3, abrogated GD-induced autophagy. Nox4
      promoted autophagy during GD through activation of the protein kinase RNA
      activated-like ER kinase pathway by suppression of prolyl hydroxylase 4. The
      decrease in cell survival during GD in the presence of Nox4 knockdown was rescued
      by reactivation of autophagy by Atg7 overexpression, indicating that the effect
      of Nox4 on cell survival is critically mediated through regulation of autophagy.
      Nox4 was activated during fasting and prolonged ischemia in the mouse heart,
      where Nox4 is also required for autophagy activation and cardioprotection.
      CONCLUSIONS: Nox4 critically mediates autophagy in response to energy stress in
      cardiomyocytes by eliciting ROS in the ER and stimulating the protein kinase RNA
      activated-like ER kinase signaling pathway.

PMID- 24081884
TI  - Sensory polymyeloradiculopathy associated with Toscana virus infection.
AB  - Sandfly viruses are arthropod-borne viruses that are endemic in the Mediterranean
      basin. The Toscana virus (TOSV) is the only serotype of sandfly viruses known to
      cause neurological symptoms in humans, usually aseptic meningitis or
      meningoencephalitis. We report a case of a 39-year-old man who was admitted to
      our department with progressive paresthesias of the lower limbs followed by
      dysesthesias of the upper thorax after a hiking trip to the Netherlands. The
      patient had also been suffering from epididymitis for several weeks before the
      neurological symptoms appeared but was treated by antibiotics accordingly. Lumber
      puncture results demonstrated mononuclear pleocytosis with elevated protein
      levels. MRI of the lumbar spine revealed polymyeloradiculopathy. Positive IgM
      antibodies against the Toscana serotype of sandfly virus were discovered in the
      patient's blood and CSF. There was also evidence for a recent infection by
      Mycoplasma pneumoniae. The patient was treated conservatively with improvement in
      his neurological state. To the best of our knowledge, this is the first case
      report of an association between TOSV infection and polymyeloradiculopathy. 

PMID- 24081883
TI  - A novel computerized functional assessment for human immunodeficiency virus
      associated neurocognitive disorder.
AB  - Human immunodeficiency virus (HIV)-associated neurocognitive disorder (HAND) is
      present in 30-60 % of HIV-positive (HIV+) individuals and can be assessed by
      neuropsychological testing and level of functional impairment. HAND diagnosis
      therefore requires accurate assessment of functional impairment. The Computer
      Assessment of Mild Cognitive Impairment (CAMCI) is a computer-based screening
      tool that includes performance-based measures of functional impairment. We sought
      to evaluate the CAMCI as a functional assessment tool in HAND. One hundred
      fourteen HIV+ patients and 38 HIV-negative (HIV-) patients underwent
      neuropsychological and CAMCI testing. Cognitive status for HIV+ subjects was
      classified using the Frascati criteria. HIV+ subjects grouped together and
      classified by cognitive impairment performed worse than HIV- subjects on several
      of the CAMCI tasks, including following directions to the supermarket (p = 0.05,
      p = 0.03), recalling which items to purchase (p = 0.01, p = 0.02), and
      remembering to stop at a supermarket (p < 0.01, p = 0.01) and the post office (p
      < 0.01, p = 0.03). After controlling for hepatitis C status and depression
      symptomatology, the tasks "following directions to the supermarket" and the
      "recalling which items to purchase" were no longer significant. The "remembering
      to run two separate errands" tasks retained their significance (p < 0.01 for both
      tasks). A subset of the CAMCI tasks therefore successfully differentiated HIV+
      patients from HIV- individuals. Differences in hepatitis C status and depression
      symptomatology could account for some of the function assessment differences in
      the CAMCI. These results suggest the CAMCI could be a useful objective
      performance-based functional assessment in patients with HIV. 

PMID- 24081885
TI  - Ventilatory response to added dead space and position in preterm infants at high
      risk age for SIDS.
AB  - OBJECTIVE: The vulnerability of prematurely born infants to sudden infant death
      syndrome (SIDS) in the prone position might be explained by a reduced ability to
      respond to a stress, such as hypercarbia, in that position; our objective,
      therefore, was to further explore the influence of position on the response to a
      stress. WORKING HYPOTHESIS: The ability of prematurely born infants to respond to
      added dead space in the prone compared to the supine position would be impaired
      at the high risk age for SIDS. PATIENTS: Twenty infants, median gestational age
      of 30 (range 24-32) weeks were studied at a median postmenstrual age (PMA) of 45
      weeks. In addition, comparisons were made to the results of 25 infants studied at
      36 weeks PMA. METHODOLOGY: Infants were studied supine and prone. Breath by
      breath minute volume was measured at baseline and after a dead space was
      incorporated into the breathing circuit; the time constant of the response was
      calculated. The pressure generated in the first 100 msec of an occlusion (P0.1 ),
      the maximum inspiratory pressure during an airway occlusion and functional
      residual capacity (FRC) were also measured in both positions. RESULTS: The median
      time constant was longer (38 (range 15-85) vs. 26 (range 2-40) sec (P = 0.002)).
      P0.1 lower (P = 0.003) and FRC higher (P = 0.031) in the prone compared to the
      supine position. In the prone position, the time constant correlated with PMA (P
      = 0.047), that is, the rate of response to added dead space was significantly
      damped with increasing postnatal age up to the critical age for SIDS.
      CONCLUSIONS: The dampened rate of response to added dead space in the prone
      compared to the supine position lends support to the hypothesis that a poorer
      response to a stress may contribute to prematurely born infants increased risk of
      SIDS in the prone position.

PMID- 24081886
TI  - Evaluation of interrupter resistance in methacholine challenge testing in
      children.
AB  - Bronchial hyperresponsiveness (BHR) is a key feature of asthma and is assessed
      using bronchial provocation tests. The primary outcome in such tests (a 20%
      decrease in forced expiratory volume in 1 sec (FEV1)) is difficult to measure in
      young patients. This study evaluated the sensitivity and specificity of the
      interrupter resistance (Rint ) technique, which does not require active patient
      participation, by comparing it to the primary outcome measure. Methacholine
      challenge tests were performed in children with a history of moderate asthma and
      BHR. Mean and individual changes in Rint and FEV1 were studied. A receiver
      operating characteristic (ROC) curve was used to describe sensitivity and
      specificity of Rint . Seventy-three children (median age: 9.2 years; range: 6.3
      13.4 years) participated. There was a significant (P < 0.01) increase in mean
      Rint with increasing methacholine doses. However, individual changes of Rint
      showed large fluctuations. There was great overlap in change of Rint between
      children who did and did not reach the FEV1 endpoint. A ROC curve showed an area
      under the curve of 0.65. Because of low sensitivity and specificity, the use of
      Rint to diagnose BHR in individual patients seems limited.

PMID- 24081887
TI  - Resource usage in outpatient care and reimbursement for cystic fibrosis in
      Germany.
AB  - OBJECTIVE: Objective of this study is to assess and evaluate resource use in
      outpatient treatment in Germany and to compare it with remuneration. METHODS:
      Outpatient treatment was evaluated in seven different centers for pediatric and
      adult CF patients. Data were recorded during one representative month in 2006. A
      micro-costing approach was used to value resource use data. RESULTS: For
      outpatient treatment mean costs (excluding drugs) of 488 ? per patient per
      quarter occurred. Correlation analyses identified significant cost drivers
      including age and co-morbidities (pancreatic insufficiency, hepatobiliary
      complications, lung function capacity, or bacterial lung colonization).
      Remuneration covered only 51% of the total costs (252 ? per patient/quarter).
      CONCLUSIONS: As the human resources available to these centers today are already
      below the requirements set by the European consensus for standards of CF care it
      will be important for a high level of patient care to reach a cost-covering
      remuneration scheme.

PMID- 24081888
TI  - [Adaptation and validation of CAMDEX-DS (Cambridge Examination for Mental
      Disorders of Older People with Down's Syndrome and others with intellectual
      disabilities) in Spanish population with intellectual disabilities].
AB  - INTRODUCTION: Dementia caused by Alzheimer's disease commonly affects the adult
      population with Down's syndrome. This population presents two characteristic
      clinical features: a semiologic pattern that differs from the typical Alzheimer's
      disease, and previous intellectual deficits that may confound the clinical
      diagnosis. There is a clear need to validate specific instruments adapted to
      Spanish population. AIM: To adapt and to validate CAMDEX-DS (Cambridge
      Examination for Mental Disorders of Older People with Down's Syndrome and Others
      with Intellectual Disabilities) in Spanish population. PATIENTS AND METHODS: 146
      patients with intellectual disability (mild to moderate) were recruited and
      assessed with CAMDEX-DS, K-BIT I and DMR tests. Test-retest reliability, inter
      rater concordance and validity statistic were performed between CAMDEX-DS and
      clinical diagnosis. This is an observational, multicenter, cross-sectional and
      validation study. RESULTS: Test-retest and inter-rater reliability achieved kappa
      coefficient values of 0.92 and 0.91, respectively. Agreement (kappa index) for
      CAMDEX-DS on clinical diagnosis compared to other clinical criteria was high:
      CAMDEX-DS vs DSM-IV (kappa = 0.95; p < 0,001); CAMDEX-DS vs ICD-10 (kappa = 0.97;
      p < 0.001). All item-test correlations ranged between 0,31 and 0,69. Internal
      reliability-calculated using Chronbach's alpha scored 0.93. CONCLUSIONS: The
      Spanish version of CAMDEX-DS is a valid instrument with high applicability for
      people with intellectual disability. It shows good psychometric properties. The
      Cambridge Cognitive Examination for Older Adults with Down's Syndrome (CAMCOG-DS)
      can set two key points by the level of intellectual disability on the suspicion
      of cognitive impairment in people with Down's syndrome.

PMID- 24081889
TI  - [A comparative study of the effectiveness of topiramate and flunarizine in
      independent series of chronic migraine patients without medication abuse].
AB  - INTRODUCTION: Topiramate and onabotulinumtoxin A have proven to be effective in
      chronic migraine with or without medication abuse according to recent criteria of
      the International Headache Society's Headache Classification. AIMS: To show that
      flunarizine is as effective as topiramate in cases of chronic migraine without
      medication abuse. PATIENTS AND METHODS: We conducted a prospective, non
      randomised, comparative study of two groups of patients paired by age and sex,
      with chronic migraine without abuse, who had been treated preventively for the
      first time with topiramate or flunarizine. RESULTS: Forty patients treated with
      flunarizine were assigned a patient of their same sex and age who was being
      treated with topiramate. The mean rate of reduction in intense migraines in the
      topiramate group was 59% and in the flunarizine group, 58.5% (p = 0.9444); the
      responder rate at four months of treatment did not show any significant
      differences either, the figures being 75% for topiramate and 70% for flunarizine
      (p = 0.6236). The mean reduction of other headaches in the topiramate group was
      57% and in the flunarizine group, 64% (p = 0.4261); the responder rate at four
      months of treatment was similar in the two groups: 76%. The percentage of
      dropouts from treatment was higher with topiramate (19.5%) than with flunarizine
      (10%) (p = 0.3493). No serious side effects occurred in either of the groups. In
      all, 78.9% of the patients who took topiramate said they were satisfied with the
      drug versus 75% of those in the flunarizine group (p = 0.7903). CONCLUSIONS:
      Flunarizine proved to be as effective as topiramate in the treatment of chronic
      migraine without medication abuse.

PMID- 24081890
TI  - [CLIPPERS syndrome with atypical distribution of lesions in magnetic resonance
      imaging of the brain].
AB  - INTRODUCTION: CLIPPERS syndrome (chronic lymphocytic inflammation with pontine
      perivascular enhancement responsive to steroids) is an inflammatory process of
      the central nervous system whose distinguishing features are the enhancing
      punctiform lesions in the brainstem that appear in the magnetic resonance images.
      Clinically, it is accompanied by dysarthria, ataxia and diplopia, and usually
      responds to treatment with corticoids. Pathologically, T lymphocytes appear
      infiltrated in the perivascular spaces of the brainstem. CASE REPORT: We report
      the case of a 40-year-old woman with an initial subacute clinical picture of
      binocular diplopia, ataxia and dysarthria. The magnetic resonance brain scan
      revealed T2 hyperintense punctiform lesions in the stem, cerebellum,
      diencephalons and cortico-subcortical areas of both hemispheres, which were
      enhanced with contrast. An aetiological study was performed to rule out any
      underlying infectious, neoplastic or inflammatory origin, the results being
      negative. The patient was treated on two occasions with methylprednisolone, with
      a gradual lowering of the dosage, the response being favourable. CONCLUSIONS:
      Diplopia and ataxia, as in our case, are practically always present. The MR
      findings consist of punctiform enhancing lesions located in the pons extending
      towards the cerebellum, basal ganglia and corpus callosum, the enhancement
      gradient becoming lower as the distance increases rostrally away from the cortex,
      and caudally towards the spinal cord. In the case of our patient, this gradient
      is not respected, and the density found was similar to that of lesions at the
      supratentorial level. The differential diagnosis is wide-ranging and justifies an
      extensive diagnostic study with, in certain cases, a biopsy study of brain
      tissue. The disease courses in a relapsing-remitting pattern and the earlier
      steroid therapy is established and the more prolonged it is, the better the
      prognosis will be.

PMID- 24081891
TI  - [Consensus document on spasticity in patients with multiple sclerosis. Grupo de
      Enfermedades Desmielinizantes de la Sociedad Espanola de Neurologia].
AB  - INTRODUCTION: Multiple sclerosis is a chronic neurological inflammatory
      demyelinating disease. Specialists involved in the symptomatic treatment of this
      disease tend to apply heterogeneous diagnostic and treatment criteria. AIM: To
      establish homogeneous criteria for treating spasticity based on available
      scientific knowledge, facilitating decision-making in regular clinical practice.
      DEVELOPMENT: A group of multiple sclerosis specialists from the Spanish
      Neurological Society demyelinating diseases working group met to review aspects
      related to spasticity in this disease and draw up the consensus. After an
      exhaustive bibliographic search and following a metaplan technique, a number of
      preliminary recommendations were established to incorporate into the document.
      Finally, each argument was classified depending on the degree of recommendation
      according to the SIGN (Scottish Intercollegiate Guidelines Network) system. The
      resulting text was submitted for review by the demyelinating disease group. An
      experts' consensus was reached regarding spasticity triggering factors, related
      symptoms, diagnostic criteria, assessment methods, quality of life and
      therapeutic management (drug and non-drug) criteria. CONCLUSION: The
      recommendations included in this consensus can be a useful tool for improving the
      quality of life of multiple sclerosis patients, as they enable improved diagnosis
      and treatment of spasticity.

PMID- 24081892
TI  - [Neuroethics as the neuroscience of ethics].
AB  - INTRODUCTION: The neurosciences have developed at a stunningly fast rate. Key
      points accounting for this progression include the introduction of functional
      neuroimaging techniques and the boost resulting from the Decade of the Brain
      project. This expansion has also allowed new disciplines such as neuroethics to
      appear. DEVELOPMENT: Those who have worked on neuroethics can be divided into
      three groups (neuroreductionists, neurosceptics and neurocritics), and each group
      has its own standpoint as regards what neuroethics is, with several scopes and
      limitations in their proposals. CONCLUSIONS: Neuroethics is a discipline that,
      prior to the year 2002, was understood only as an ethics of neuroscience (a
      branch of bioethics). As of that date, however, it is also understood as a
      neuroscience of ethics (a new discipline). Neuroreductionism proposes that all
      ethical life has a basis in the brain that determines ethical actions;
      neuroscepticism holds that neuroscience cannot be considered a normative
      function; and neurocriticism considers that the neuroscientific advances cannot
      be ignored and must be taken into account in some way in order to draw up ethical
      theories.

PMID- 24081893
TI  - [Non-traumatic myelopathies in a district hospital: an epidemiological
      descriptive study of 68 cases].

PMID- 24081894
TI  - [Epilepsy in films. A new century and... the same old perspective?].

PMID- 24081895
TI  - Recurrent oral thrush.
AB  - Autoimmune polyendocrinopathy syndrome type 1 (APS-1) is characterized by the
      presence of at least two out of three clinical features, which include chronic
      mucocutaneous candidiasis (CMC), Addison's disease and hypoparathyroidism. The
      authors' present an one and a half year old girl with recurrent oral thrush who
      presented with generalised afebrile seizure. Evaluation revealed severe
      hypocalcemia with low parathormone and normal vitamin D level consistent with
      hypoparathyroidism. In view of the oral candidiasis and hypoparathyroidism, a
      clinical possibility of autoimmune polyglandular syndrome (type 1) was strongly
      considered. Her mother, on subsequent pregnancy was subjected to gene analysis of
      the fetus (chorionic villus sampling) and also for this child (index case). Both
      the fetus and index child were confirmed to have the AIRE gene mutation of APS1.
      After detailed counseling the parents opted for medical termination of the
      pregnancy. In children who present with recurrent oral thrush we need to consider
      but also look beyond immunodeficiency.

PMID- 24081896
TI  - Evaluation of Integrated Management of Neonatal and Childhood Illness (IMNCI)
      algorithm for diagnosis and referral in under-five children.
AB  - A prospective observational study was conducted on 500 children to evaluate the
      Integrated Management of Neonatal and Childhood Illnesses (IMNCI) algorithm for
      diagnosis and referral of children aged 0-59 mo. IMNCI algorithm performed well
      in diagnosis [except sepsis in 0-7 d (p < 0.01) and malaria in 2-59 mo (p <
      0.01)] and referral of under five illnesses. The proportion of children with the
      mismatch between 'IMNCI' diagnosis and 'Gold Standard' diagnosis were highest
      (38.7 %) among children 0-7 d of age. The authors conclude that IMNCI algorithm
      in young children has good sensitivity for referring children with severe
      illnesses and is a good tool for diagnosis of most of childhood illnesses in
      under-five children.

PMID- 24081898
TI  - IL-6 trans-signaling enhances CCL20 production from IL-1beta-stimulated human
      periodontal ligament cells.
AB  - CC chemokine ligand 20 (CCL20) plays a central role in the recruitment of CCR6
      expressing cells, including Th17 cells which are related to bone resorption in
      periodontal lesions and thus in the development of periodontal disease. IL-6 is
      an important cytokine that is associated with the pathogenesis of periodontitis.
      However, the effect of IL-6 on CCL20 production is uncertain. The aim of this
      study was to examine whether IL-6 could modify CCL20 expression in human
      periodontal ligament cells (HPDLCs). HPDLCs expressed gp130 but did not express
      IL-6R on the surface of HPDLCs. So, IL-6 trans-signaling is important to
      recognize IL-6 by HPDLCs. IL-6/sIL-6R stimulation enhanced CCL20 production in IL
      1beta-stimulated HPDLCs. IL-6 produced from IL-1beta-stimulated HPDLCs with sIL
      6R could increase CCL20 production in HPDLCs with sIL-6R. Signal transducer and
      activator of transcription (STAT)3 activation was related to CCL20 production in
      IL-1beta and IL-6/sIL-6R-stimulated HPDLCs. Our data suggests that HPDLCs, in
      response to IL-6, sIL-6R, and IL-1beta, may shift chemokine production to that
      favoring CCR6-expressing cells recruitment in periodontal lesions. 

PMID- 24081900
TI  - Reducing inequality is crucial to implementing universal health coverage, says
      WHO report.

PMID- 24081899
TI  - The syndemic condition of psychosocial problems and HIV risk among male sex
      workers in Ho Chi Minh City, Vietnam.
AB  - In Vietnam, the co-occurrence (i.e., "syndemic") of psychosocial factors (e.g.,
      depression and substance use) may disproportionately burden male sex workers and
      increase their HIV risk. A comprehensive survey was conducted among 300 male sex
      workers in Ho Chi Minh City, Vietnam in 2010. We performed logistic regression to
      examine the association between the syndemic variable-a count score of the number
      of five psychosocial conditions endorsed-and unprotected anal sex (UAS) in the
      past. One-third of participants reported any UAS, and 42 % reported >=2
      psychosocial health problems. In multivariable models, experiencing >=4
      psychosocial health problems was significantly associated with UAS. Every unit
      increase in number of psychosocial health problems was associated with a 25-30 %
      increase in odds of UAS. Understanding the syndemic condition and its association
      with HIV risk among male sex workers in Vietnam may lead to the development of
      more effective, comprehensive interventions.

PMID- 24081901
TI  - European regulator is urged to release data on drugs approved in past 10 years.

PMID- 24081902
TI  - GPs in Hackney win bid to run out of hours service.

PMID- 24081904
TI  - Increased expression of CYP24A1 correlates with advanced stages of prostate
      cancer and can cause resistance to vitamin D3-based therapies.
AB  - A major limitation of exogenous vitamin D3 administration for the treatment of
      prostate cancer is the marginal, if any, clinical efficacy. We dissected the
      basis for the resistance to the vitamin D3 antitumor properties and specifically
      examined the effect of its major catabolic enzyme, CYP24A1, in prostate cancer.
      Local CYP24A1 expression levels and the effect of selective modulation were
      analyzed using tissue microarrays from needle core biopsy specimens and xenograft
      bearing mouse models. CYP24A1 mRNA was elevated in malignant human prostate
      tissues compared to benign lesions. High CYP24A1 protein levels were seen in
      poorly differentiated and highly advanced stages of prostate cancer and
      correlated with parallel increase in the tumor proliferation rate. The use of
      CYP24A1 RNAi enhanced the cytostatic effects of vitamin D3 in human prostate
      cancer cells. Remarkably, subcutaneous and orthotopic xenografts of prostate
      cancer cells harboring CYP24A1 shRNA resulted in a drastic reduction in tumor
      volume when mice were subjected to vitamin D3 supplementation. CYP24A1 may be a
      predictive marker of vitamin D3 clinical efficacy in patients with advanced
      prostate cancer. For those with up-regulated CYP24A1, combination therapy with
      RNAi targeting CYP24A1 could be considered to improve clinical responsiveness to
      vitamin D3.

PMID- 24081905
TI  - AKT3 controls mitochondrial biogenesis and autophagy via regulation of the major
      nuclear export protein CRM-1.
AB  - Our previous work has shown that Akt3 is required for mitochondrial biogenesis in
      primary human endothelial cells (ECs) and in Akt3-null mice; Akt3 affects
      subcellular localization of peroxisome proliferator-activated receptor gamma
      coactivator-1 (PGC-1alpha), the master regulator of mitochondrial biogenesis. The
      purpose of this study is to determine the mechanism by which Akt3 controls the
      subcellular distribution of PGC-1alpha and to explore the effect on mitochondrial
      biogenesis and turnover during angiogenesis. Here we use standard biochemical
      analyses and Akt3-knockdown strategies to show that Akt3 controls the
      stabilization of chromosome maintenance region-1 (CRM-1), the major nuclear
      export receptor. Site-directed mutagenesis and association analyses show that PGC
      1alpha nuclear export is CRM-1 dependent. Akt3 knockdown and CRM-1 overexpression
      cause 3-fold reductions in PGC-1alpha target gene expression, compared to control
      levels. Akt3 inhibition causes autophagy, as measured by autophagosome formation,
      in a CRM-1-dependent, Akt1/mTOR-independent pathway. In vivo, Akt3-null and
      heterozygous mice show dose-dependent decreases in angiogenesis compared to wild
      type littermates (~5- and 2.5-fold decreases, respectively), as assessed by
      Matrigel plug assays. This correlates with an ~1.5-fold decrease in mitochondrial
      Cox IV expression. Our studies suggest that Akt3 is a regulator of mitochondrial
      dynamics in the vasculature via regulation of CRM-1-dependent nuclear export.

PMID- 24081906
TI  - Role of mitofusin 2 (Mfn2) in controlling cellular proliferation.
AB  - It has been reported that Mitofusin2 (Mfn2) inhibits cell proliferation when
      overexpressed. We wanted to study the role of endogenous Mfn2 in cell
      proliferation, along with the structural features of Mfn2 that influence its
      mitochondrial localization and control of cell proliferation. Mfn2-knockdown
      clones of a B-cell lymphoma cell line BJAB exhibited an increased rate of cell
      proliferation. A 2-fold increase in cell proliferation was also observed in Mfn2
      knockout mouse embryonic fibroblast (MEF) cells as compared with the control wild
      type cells, and the proliferative advantage of the knockout MEF cells was blocked
      on reintroduction of the Mfn2 gene. Mfn2 exerts its antiproliferative effect by
      acting as an effector molecule of Ras, resulting in the inhibition of the Ras-Raf
      ERK signaling pathway. Furthermore, both the N-terminal (aa 1-264) and the C
      terminal (aa 265-757) fragments of Mfn2 blocked cell proliferation through
      distinct mechanisms: the N-terminal-mediated inhibition was due to its
      interaction with Raf-1, whereas the C-terminal fragment of Mfn2 inhibited cell
      proliferation by interacting with Ras. The inhibition of proliferation by the N
      terminal fragment was independent of its mitochondrial localization.
      Collectively, our data provide new insights regarding the role of Mfn2 in
      controlling cellular proliferation.

PMID- 24081907
TI  - PEGylated liposomal Gemcitabine: insights into a potential breast cancer
      therapeutic.
AB  - PURPOSE: Nanoencapsulation of chemotherapeutics is an established method to
      target breast tumors and has been shown to enhance the efficacy of therapy in
      various animal models. During the past two decades, the nucleoside analog
      Gemcitabine has been under investigation to treat both recalcitrant and localized
      breast cancer, often in combination with other chemotherapeutics. In this study,
      we investigated the chemotherapeutic efficacy of a novel Gemcitabine-encapsulated
      liposome previously formulated by our group, GemPo, on both sensitive (4T1) and
      recalcitrant (MDA-MB-231) breast cancer cell lines. METHODS: Gemcitabine free
      drug and liposomal Gemcitabine were compared both in vitro and in vivo using
      breast cancer models. RESULTS: We demonstrated that GemPo differently hindered
      the growth, survival and migration of breast cancer cells, according to their
      drug sensitivities. Specifically, whereas GemPo was a more potent cytotoxic and
      apoptotic agent in sensitive breast cancer cells, it more potently inhibited cell
      migration in the resistant cell line. However, GemPo still acted as a more potent
      inhibitor of migration, in comparison with free Gemcitabine, irrespective of cell
      sensitivity. Administration of GemPo in a 4T1-bearing mouse model inhibited tumor
      growth while increasing mice survival, as compared with free Gemcitabine and a
      vehicle control. Interestingly, the inclusion of a mitotic inhibitor, Paclitaxel,
      synergized only with free Gemcitabine in this model, yet was as effective as
      GemPo alone. However, inclusion of Paclitaxel with GemPo significantly improved
      mouse survival. CONCLUSIONS: Our study is the first to demonstrate the
      pleiotropic effects of Gemcitabine and Gemcitabine-loaded nanoparticles in breast
      cancer, and opens the door for a novel treatment for breast cancer patients.

PMID- 24081908
TI  - Clear cell cystic variant of calcifying epithelial odontogenic tumor.
AB  - Calcifying epithelial odontogenic tumor (CEOT) is a solid, locally aggressive,
      benign odontogenic neoplasm characterized by sheets and nests of polyhedral
      epithelial cells exhibiting eosinophilic and less often clear cytoplasm,
      occasional nuclear pleomorphism without mitotic activity, calcifications, and
      deposits of amyloid. A cystic variant has been reported only twice. Herein, we
      present an additional example of cystic CEOT occurring in a 31-year-old male and
      featuring clear cell epithelial lining with deposits of amyloid and osteodentin. 

PMID- 24081909
TI  - The neuronal genome of Caenorhabditis elegans.
AB  - The ~100 MB genome of C. elegans codes for ~20,000 protein-coding genes many of
      which are required for the function of the nervous system, composed of 302
      neurons in the adult hermaphrodite and of 383 neurons in the adult male. In
      addition to housekeeping genes, a differentiated neuron is thought to express
      many hundreds if not thousands of genes that define its functional properties.
      These genes code for ion channels, G-protein-coupled receptors, neurotransmitter
      synthesizing enzymes, transporters and receptors, neuropeptides and their
      receptors, cell adhesion molecules, motor proteins, signaling molecules and many
      others. Collectively such genes have been referred to as "terminal
      differentiation genes" or "effector genes". The differential expression of
      distinct combinations of terminal differentiation genes define different neuron
      types. This paper provides a compendium of more than 2,800 putative terminal
      differentiation genes. One pervasive theme revealed by the analysis of many gene
      families is the nematode-specific expansions of many neuron function-related gene
      families, including, for example, many types of ion channel families, sensory
      receptors and neurotransmitter receptors. The gene lists provided here can serve
      multiple purposes. They can serve as quick reference guides for individual gene
      families or they can be used to mine large datasets (e.g., expression datasets)
      for genes with likely functions in the nervous system. They also serve as a
      starting point for future projects. For example, a comprehensive understanding of
      the regulation of the often complex expression patterns of these genes in the
      nervous system will eventually explain how nervous systems are built.

PMID- 24081910
TI  - Control of Alicyclobacillus acidoterrestris in fruit juices by a newly discovered
      bacteriocin.
AB  - Alicyclobacillus acidoterrestris is one of the most spoilage-causing bacteria in
      fruit juices. Control of A. acidoterrestris in fruit juices by bificin C6165 (Pei
      et al. in J Appl Microbiol 114(5):1273-1284, 2013), a bacteriocin produced by
      Bifidobacterium animalis subsp. animalis CICC 6165, was described in this study.
      Activity spectrum of bificin C6165 was investigated and sixteen strains of A.
      acidoterrestris were sensitive to bificin C6165 in diluted Apple Juices. In the
      commercial fruit juices, vegetative cells of A. acidoterrestris were inactivated
      by bificin C6165 at 40 MUg/ml. The inhibitory effect of bificin C6165 was better
      at lower pH (pH 3.5) and at a higher temperature of 45  degrees C. Furthermore,
      electron microscopy examination of the vegetative cells treated with bacteriocin
      revealed substantial cell damage and bacterial lysis. The result suggested that
      primary mode of action of bificin C6165 was most probably due to pore formation.
      Although no significantly activity of bificin C6165 was observed against the
      endospores of A. acidoterrestris in commercial apple juice, the addition of
      bacteriocin contributed to the reduction of the thermal resistance of A.
      acidoterrestris spores. Additionally, encapsulation of bificin C6165 with Ca
      alginate gel was investigated. Encapsulation of bificin C6165 provided a
      promising method to control A. acidoterrestris in food juice industry. 

PMID- 24081911
TI  - Utilization of palm oil decanter cake as a novel substrate for biosurfactant
      production from a new and promising strain of Ochrobactrum anthropi 2/3.
AB  - A biosurfactant-producing bacterium, isolate 2/3, was isolated from mangrove
      sediment in the south of Thailand. It was evaluated as a potential biosurfactant
      producer. The highest biosurfactant production (4.52 g/l) was obtained when the
      cells were grown on a minimal salt medium containing 25 % (v/v) palm oil decanter
      cake and 1 % (w/v) commercial monosodium glutamate as carbon and nitrogen
      sources, respectively. After microbial cultivation at 30  degrees C in an
      optimized medium for 96 h, the biosurfactant produced was found to reduce the
      surface tension of pure water to 25.0 mN/m with critical micelle concentrations
      of 8.0 mg/l. The stability of the biosurfactant at different salinities, pH and
      temperature and also its emulsifying activity was investigated. It is an
      effective surfactant at very low concentrations over a wide range of
      temperatures, pH and salt concentrations. The biosurfactant obtained was
      confirmed as a glycolipid type biosurfactant by using a biochemical test, fourier
      transform infrared spectroscopy, MNR and mass spectrometry. The crude
      biosurfactant showed a broad spectrum of antimicrobial activity and also had the
      ability to emulsify oil and enhance polyaromatic hydrocarbons solubility. 

PMID- 24081912
TI  - Construction of a heterologous gene expression system in the banana
      rhizobacterium strain GW-3 and its colonization ability.
AB  - Rhizobacteria inhabiting the rhizosphere are beneficial to their host plants, and
      can potentially serve as biocontrol agents to control plant diseases. We isolated
      the rhizobacterium strain GW-3, which was the dominant bacterium in the
      rhizosphere soils of healthy banana plants. Then, we constructed an expression
      system with a kanamycin resistance gene to express a heterologous protein in GW
      3. Using the green fluorescent protein gene as the reporter, we monitored
      expression of the heterologous protein by detecting fluorescence intensity and
      conducting western blot analyses. The standard fluorescence intensity of the
      recombinant strain reached 1,482 +/- 3.49 RFU. To study the colonization ability
      of GW-3, we inoculated this bacterium into sterilized and unsterilized
      rhizosphere soils and monitored the bacterial population over 25 days. The
      populations of GW-3 in rhizosphere soils first increased, then decreased, and
      finally reached a balance. Laser scanning confocal microscope analyses of
      fluorescence in banana roots after inoculation with GW-3 confirmed that the
      recombinant GW-3 strain stably colonized banana root surfaces. Analyses of the
      bacterial population in unsterilized rhizosphere soils showed that the
      recombinant GW-3 strain was still the dominant bacterium in banana rhizosphere
      soils at 25 days after inoculation. Together, these results showed that this
      expression system can be used to express a heterologous protein at high levels in
      a dominant rhizobacterium. By incorporating relevant resistance genes into the
      expression system, this method could be used to genetically engineer GW-3 to
      control banana wilt disease. 

PMID- 24081914
TI  - Ability of non-ophthalmologist doctors to detect eyes with occludable angles
      using the flashlight test.
AB  - The aim of this study is to assess the ability of non-ophthalmologist doctors to
      detect eyes with occludable angles using the flashlight test (FLT). For this
      study, a total of 45 patients were prospectively enrolled. After an
      ophthalmological examination all patients underwent FLT by two non
      ophthalmologist examiners in a masked and standardized fashion. Two gynecologists
      were chosen, as they often deal with patients exposed to drugs that can trigger
      pupillary block. An occludable angle was defined as >=2 quadrants in which the
      posterior trabecular meshwork was not visible by gonioscopy without indentation
      (performed by an experienced glaucoma specialist). Whenever both eyes were
      eligible, one was randomly selected for analysis. Sensitivity and specificity for
      detection of occludable angles were generated, and the agreement between
      examiners was assessed. This study results showed that the mean age was 47.1 +/-
      16.4 years and most patients were female (67.7 %). There was a good agreement
      between observers for FLT results (kappa = 0.77; p = 0.04). Similar values of
      sensitivity and specificity were found for both examiners (92 and 67 % vs 97 and
      67 %, respectively). Based on the findings of this study, it was concluded that
      FLT showed good sensitivity for detection of eyes with occludable angles. The
      fact that it can be easily and reliably performed by non-ophthalmologist
      highlights its use as a screening tool in patients requiring medications that can
      induce angle closure.

PMID- 24081915
TI  - Analyses of surgically induced astigmatism and axis deviation in microcoaxial
      phacoemulsification.
AB  - To evaluate surgically induced astigmatism (SIA) and axis deviation after coaxial
      microincision superotemporal clear corneal phacoemulsification incision in eyes
      with differently located steep axis. This prospective, comparative study included
      four groups of 45 eyes with age-related cataracts; each group underwent 2.2-mm
      superotemporal clear corneal incision (CCI) cataract surgery. The four groups of
      patients were divided by location of the steep axis. Groups were matched
      according to symmetry of the steep axis for both right and left eyes as follows-
      0 degrees -45 degrees  of steep axis for right eyes, and 136 degrees -180 degrees
      for left eyes (group 1); 46 degrees -90 degrees  for right eyes and 91 degrees 
      135 degrees  for left eyes (group 2); 91 degrees -135 degrees  for right eyes and
      46 degrees -90 degrees  for left eyes (group 3); and 136 degrees -180 degrees 
      for right eyes and 0 degrees -45 degrees  for left eyes (group 4). Outcome
      measures included changes in mean total astigmatism, SIA, and axis deviation.
      Astigmatism was measured by manual keratometry readings before surgery and week
      1, week 4, week 8, and week 12 postoperatively. SIA was calculated by the vector
      analysis (Holladay-Cravy-Koch method). The magnitude of mean total astigmatism
      was lowest in group 3 and highest in group 1 at week 12. SIA was 0.39 diopters
      (D), 0.22 D, 0.17 D, and 0.28 D in group 1, group 2, group 3, and group 4,
      respectively. The change in astigmatic axis deviation was highest in group 3
      (23.6 +/- 16.6) (P < 0.05). Axis deviation and SIA were stable after week 4.
      Planning of CCI on or near the steep axis can help decrease corneal astigmatism.

PMID- 24081913
TI  - Etiological agents of fungal endophthalmitis: diagnosis and management.
AB  - Endophthalmitis caused by fungi is commonly diagnosed around the world in
      apparently healthy and immunocompromised individuals. An accurate clinical
      diagnosis for endophthalmitis confirmed by laboratory techniques is essential for
      early treatment with antifungal drugs, such as amphotericin B, imidazoles, and
      other antifungals. Here, we review endophthalmitis caused by fungi according to
      its classification into endogenous fungal endophthalmitis (EFE) and exogenous
      fungal endophthalmitis (EXFE). EFE is caused by endogenously acquired fungi,
      whereas the traumatic implantation of opportunistic fungal pathogens is the main
      feature of EXFE. We highlight the most important etiologies causing
      endophthalmitis and the steps required for a rapid diagnosis and management. 

PMID- 24081916
TI  - Early and sustained treatment modifies the phenotype of birdshot
      retinochoroiditis.
AB  - In this single-centre retrospective case review, we investigate the long-term
      follow-up of birdshot retinochoroiditis (BRC) patients, analysing the impact of
      early, vigorous, and prolonged treatment on the evolution of indocyanine green
      angiography (ICGA) signs and fundus appearance. Treatment delay was calculated
      for each BRC patient, and patients were classified into two groups--treatment
      delay of <10 months (early-treatment group) and treatment delay of >10 months
      (delayed-treatment group). Fundus photographs and ICGA frames from the initial
      visit and from the last follow-up visit were assessed. Fundus photographs were
      evaluated for the presence of at least three circumpapillary, typical, rice
      shaped birdshot lesions in one eye, inferior or nasal to the optic disc. ICGA
      pictures were evaluated for the presence of lesions (hypofluorescent dark dots,
      fuzziness). Differences were compared between the two groups and between the
      first visit and the last follow-up visit. In the early-treatment group, 5/6
      patients had no characteristic BRC fundus lesions, but 7/7 patients in the
      delayed-treatment group displayed typical lesions. At last follow-up, 5/6 early
      treatment patients showed no fundus lesions, and 6/7 delayed-treatment patients
      retained their fundus lesions. At presentation, all 13 patients exhibited lesions
      on ICGA. At last follow-up, ICGA lesions had completely disappeared in 4/6 early
      treatment patients and 3/7 delayed-treatment patients. Thus, early and
      sufficiently dosed inflammation-suppressive treatment can prevent the appearance
      of typical BRC fundus lesions. It is therefore crucial to perform ICGA to detect
      otherwise occult stromal choroiditis in suspected BRC cases and to initiate
      adequate therapy immediately.

PMID- 24081917
TI  - Silicone oil pupillary block after laser retinopexy in aphakic eyes with presumed
      closed peripheral iridectomy: report of three cases.
AB  - Closure of the peripheral iridectomy (PI) may lead to forward displacement of
      silicone oil (SO) in some but not all SO-filled aphakic eyes. In this study, we
      report three patients with a history of a combined three-port pars plana
      vitrectomy and cataract surgery, SO injection and inferior PI who underwent laser
      retinopexy a few months postoperatively. The postoperative courses of these
      patients were unremarkable except for the closure of the PI without anterior
      displacement of SO; however, a few hours after laser therapy the SO was displaced
      to the anterior chamber, leading to acute glaucoma in one of the cases. Yttrium
      aluminium garnet (YAG) laser was successfully used to reopen the PI in all three
      patients. The induction of a pupillary block following laser retinopexy in SO
      filled aphakic eyes with a closed PI and no forward displacement of SO
      underscores the necessity of a follow-up examination after laser therapy in such
      patients and the importance of the prophylactic use of a YAG laser to reopen the
      PI before laser therapy. 

PMID- 24081918
TI  - Diaries for observation or intervention of health behaviors: factors that predict
      reactivity in a sexual diary study of men who have sex with men.
AB  - BACKGROUND: Behavioral diaries for observation of health-related behaviors assume
      absence of reactivity (i.e., change in behavior resulting from observation),
      while self-monitoring diaries maximize reactivity for behavior change. Little is
      known about when and for whom behavioral diary studies become self-monitoring
      interventions. PURPOSE: This study evaluated the moderating effects of social
      cognitive variables on reactivity in sexual risk behavior and risk appraisals in
      a diary study of men who have sex with men (MSM). METHODS: One hundred forty
      three MSM completed weekly online sexual diaries for 3 months. Analyses were
      conducted with hierarchical linear modeling. RESULTS: There was no evidence of
      reactivity for the sample as a whole. Social cognitive variables (e.g., risk
      reduction motivation, condom use intentions, and social norms) moderated
      reactivity in study outcomes. For example, more highly motivated MSM experienced
      declines in serodiscordant unprotected anal intercourse over time. CONCLUSIONS:
      Effectiveness of behavioral self-monitoring strategies may vary depending on
      social cognitive domains.

PMID- 24081919
TI  - The role of individual differences in cognitive training and transfer.
AB  - Working memory (WM) training has recently become a topic of intense interest and
      controversy. Although several recent studies have reported near- and far-transfer
      effects as a result of training WM-related skills, others have failed to show far
      transfer, suggesting that generalization effects are elusive. Also, many of the
      earlier intervention attempts have been criticized on methodological grounds. The
      present study resolves some of the methodological limitations of previous studies
      and also considers individual differences as potential explanations for the
      differing transfer effects across studies. We recruited intrinsically motivated
      participants and assessed their need for cognition (NFC; Cacioppo & Petty Journal
      of Personality and Social Psychology 42:116-131, 1982) and their implicit
      theories of intelligence (Dweck, 1999) prior to training. We assessed the
      efficacy of two WM interventions by comparing participants' improvements on a
      battery of fluid intelligence tests against those of an active control group. We
      observed that transfer to a composite measure of fluid reasoning resulted from
      both WM interventions. In addition, we uncovered factors that contributed to
      training success, including motivation, need for cognition, preexisting ability,
      and implicit theories about intelligence. 

PMID- 24081920
TI  - Multi-elements atmospheric deposition study in Albania.
AB  - For the first time, the moss biomonitoring technique and inductively coupled
      plasma-atomic emission spectrometric (ICP-AES) analytical technique were applied
      to study multi-element atmospheric deposition in Albania. Moss samples (Hypnum
      cupressiforme) were collected during the summer of 2011 and September-October
      2010 from 62 sites, evenly distributed over the country. Sampling was performed
      in accordance with the LRTAP Convention-ICP Vegetation protocol and sampling
      strategy of the European Programme on Biomonitoring of Heavy Metal Atmospheric
      Deposition. ICP-AES analysis made it possible to determine concentrations of 19
      elements including key toxic metals such as Pb, Cd, As, and Cu. Cluster and
      factor analysis with varimax rotation was applied to distinguish elements mainly
      of anthropogenic origin from those predominantly originating from natural
      sources. Geographical distribution maps of the elements over the sampled
      territory were constructed using GIS technology. The median values of the
      elements in moss samples of Albania were high for Al, Cr, Ni, Fe, and V and low
      for Cd, Cu, and Zn compared to other European countries, but generally were of a
      similar level as some of the neighboring countries such as Bulgaria, Croatia,
      Kosovo, Macedonia, and Romania. This study was conducted in the framework of ICP
      Vegetation in order to provide a reliable assessment of air quality throughout
      Albania and to produce information needed for better identification of
      contamination sources and improving the potential for assessing environmental and
      health risks in Albania, associated with toxic metals. 

PMID- 24081921
TI  - Microbially assisted phytoremediation approaches for two multi-element
      contaminated sites.
AB  - Phytoremediation is an environmental friendly, cost-effective technology for a
      soft restoration of abandoned mine sites. The grasses Agrostis capillaris,
      Deschampsia flexuosa and Festuca rubra, and the annual herb Helianthus annuus
      were combined with microbial consortia in pot experiments on multi-metal polluted
      substrates collected at a former uranium mine near Ronneburg, Germany, and a
      historic copper mine in Kopparberg, Sweden, to test for phytoextraction versus
      phytostabilization abilities. Metal uptake into plant biomass was evaluated to
      identify optimal plant-microbe combinations for each substrate. Metal
      bioavailability was found to be plant species and element specific, and
      influenced by the applied bacterial consortia of 10 strains, each isolated from
      the same soil to which it was applied. H. annuus showed high extraction capacity
      for several metals on the German soil independent of inoculation. Our study could
      also show a significant enhancement of extraction for F. rubra and A. capillaris
      when combined with the bacterial consortium, although usually grasses are
      considered metal excluder species. On the Swedish mixed substrate, due to its
      toxicity, with 30 % bark compost, A. capillaris inoculated with the respective
      consortium was able to extract multi-metal contaminants.

PMID- 24081922
TI  - Establishment of reference conditions for nutrients in an intensive agricultural
      watershed, Eastern China.
AB  - Nutrient enrichment from nonpoint source pollution is one of the main causes of
      poor water quality and biotic impairment in many streams and rivers worldwide.
      The establishment of reference nutrient conditions in a river system is an
      essential but difficult task for water quality control. In the present study, the
      reference concentrations of total nitrogen (TN) and total phosphorus (TP) were
      estimated in an intensive agricultural watershed, the Cao-E River system of
      Eastern China. Based on a 3-year water quality monitoring data in the river
      system, three approaches were adopted to establish the reference concentrations
      of TN and TP, those are the 75th percentile of frequency distribution of nutrient
      concentrations in reference streams, the 25th percentile of frequency
      distribution of nutrient concentration in general streams (including reference
      and non-reference streams) and regression modeling. Results showed that the
      nutrient reference concentrations were slightly different from different
      approaches. By the three approaches, the average reference concentrations for TN
      and TP in the study system were 1.73 +/- 0.13 mg l(-1) and 55.23 +/- 4.77 MUg l(
      1) with CV of 7.39 % and 8.63 %, respectively. Accordingly, the reference
      concentrations for TN and TP were recommended to be 1.70 mg l(-1) and 55 MUg l(
      1), respectively. In the mountainous and intensive agricultural watershed, the
      major anthropogenic impacts to river water quality were the urban area percentage
      cover, cropland area with slopes 0-8 degrees , and livestock and poultry waste
      loads density. These variables could account for 89.7 % and 80.3 % of the total
      variations for TN and TP concentration, respectively.

PMID- 24081923
TI  - Study of the SRF-derived ashes melting behavior and the effects generated by the
      optimization of their composition on the furnaces energy efficiency in the
      incineration plants.
AB  - As regards the incineration process of the urban solid waste, the composition
      correct management allows not only the valorization of precise civil and
      industrial groups of waste as alternative fuels but also a considerable increase
      of the furnace work temperature leading to a remarkable improvement of the
      related energy efficiency. In this sense, the study of the melting behavior of
      ashes deriving from several kinds of fuels that have to be processed to heat
      treatment is really important. This approach, indeed, ensures to know in depth
      the features defining the melting behavior of these analyzed samples, and as a
      consequence, gives us the necessary data in order to identify the best mixture of
      components to be incinerated as a function of the specific working temperatures
      of the power plant. Firstly, this study aims to find a way to establish the
      softening and melting temperatures of the ashes because they are those parameters
      that strongly influence the use of fuels. For this reason, in this work, the
      fusibility of waste-derived ashes with different composition has been
      investigated by means of the heating microscope. This instrument is fundamental
      to prove the strict dependence of the ashes fusion temperature on the heating
      rate that the samples experienced during the thermal cycle. In addition, in this
      work, another technological feature of the instrument has been used allowing to
      set an instantaneous heating directly on the sample in order to accurately
      reproduce the industrial conditions which characterize the incineration plants.
      The comparison between the final results shows that, in effect, the achievement
      of the best performances of the furnace is due to the a priori study of the
      melting behavior of the single available components. 

PMID- 24081924
TI  - Model-directed engineering of "difficult-to-express" monoclonal antibody
      production by Chinese hamster ovary cells.
AB  - Despite improvements in volumetric titer for monoclonal antibody (MAb) production
      processes using Chinese hamster ovary (CHO) cells, some "difficult-to-express"
      (DTE) MAbs inexplicably reach much lower process titers. These DTE MAbs require
      intensive cell line and process development activity, rendering them more costly
      or even unsuitable to manufacture. To rapidly and rationally identify an optimal
      strategy to improve production of DTE MAbs, we have developed an engineering
      design platform combining high-yielding transient production, empirical modeling
      of MAb synthesis incorporating an unfolded protein response (UPR) regulatory loop
      with directed expression and cell engineering approaches. Utilizing a panel of
      eight IgG1 lambda MAbs varying >4-fold in volumetric titer, we showed that MAb
      specific limitations on folding and assembly rate functioned to induce a
      proportionate UPR in host CHO cells with a corresponding reduction in cell growth
      rate. Derived from comparative empirical modeling of cellular constraints on the
      production of each MAb we employed two strategies to increase production of DTE
      MAbs designed to avoid UPR induction through an improvement in the rate/cellular
      capacity for MAb folding and assembly reactions. Firstly, we altered the
      transfected LC:HC gene ratio and secondly, we co-expressed a variety of molecular
      chaperones, foldases or UPR transactivators (BiP, CypB, PDI, and active forms of
      ATF6 and XBP1) with recombinant MAbs. DTE MAb production was significantly
      improved by both strategies, although the mode of action was dependent upon the
      approach employed. Increased LC:HC ratio or CypB co-expression improved cell
      growth with no effect on qP. In contrast, BiP, ATF6c and XBP1s co-expression
      increased qP and reduced cell growth. This study demonstrates that expression
      engineering strategies to improve production of DTE proteins in mammalian cells
      should be product specific, and based on rapid predictive tools to assess the
      relative impact of different engineering interventions.

PMID- 24081925
TI  - Causes of death in HIV-infected patients from the Cologne-Bonn cohort.
AB  - PURPOSE: Causes of death in human immunodeficiency virus (HIV)-infected subjects
      have changed in countries with high resources over the last several years.
      Acquired immunodeficiency syndrome (AIDS)-related diseases have become less
      prevalent, whereas deaths due to non-AIDS causes are increasing. The aim of the
      present study was to analyse causes of death in the Cologne-Bonn cohort. METHODS:
      Causes of death from the Cologne-Bonn cohort between 2004 and 2010 were
      systematically recorded using the CoDe algorithm (The Coding Causes of Death in
      HIV Project). RESULTS: In 3,165 patients followed from 2004 to 2010, 182 deaths
      occurred (5.7 %, 153 males, 29 females). The median age at the time of death was
      47 years (range 24-85 years). The most frequent causes of death were AIDS
      defining events (n = 60, 33 %), with non-Hodgkin lymphoma (NHL) (n = 29, 16 %)
      and infections (n = 20, 11 %) being the leading entities in this category. Non
      AIDS malignancies accounted for 16 % (n = 29), non-HIV-related infections for 10
      % (n = 18), cardiovascular diseases for 7 % (n = 14), suicide or accident for 4 %
      (n = 7) and liver diseases for 3 % (n = 5) of deaths (unknown n = 47, 26 %).
      Although the majority of patients (92.5 %) was on antiretroviral therapy (ART),
      only 50 % were virologically suppressed (HIV-RNA <50 copies/mL) and 44 % had a
      decreased CD4+ count (<200/MUL) at their last visit before death. CONCLUSION: One
      third of the causes of death in our cohort between 2004 and 2010 was AIDS
      related. Since most of these deaths occur with severe immune suppression, they
      can possibly be prevented by the early diagnosis and treatment of HIV infection.
      Care providers must be aware of an increased risk for a broad range of diseases
      in HIV-infected patients and should apply appropriate preventive measures.

PMID- 24081926
TI  - Early coagulation disorder after allogeneic stem cell transplantation is a strong
      prognostic factor for transplantation-related mortality, and intervention with
      recombinant human thrombomodulin improves the outcome: a single-center
      experience.
AB  - We retrospectively analyzed 60 cases of pediatric patients who received
      allogeneic stem cell transplantation (SCT) between 2000 and 2008, using the
      tentative scoring system for evaluation of early (<30 days) coagulation
      disorders. In the 41 patients who survived, D-dimer levels showed a transient
      increase 2 weeks after SCT and normalized thereafter, but these levels were
      persistently elevated in the 19 patients who died. Of 19 patients with a positive
      score, 11 died of transplantation-related complications [transplantation-related
      mortality (TRM) = 0.579] within 1 year, while none of the 41 with a negative
      score died during the same period. Since 2009, 12 of 30 patients had positive
      scores within 30 days after SCT. Intervention with recombinant human
      thrombomodulin (rhTM) was introduced for patients with a positive score, and 10
      of these patients survived (TRM = 0.167) along with a dramatic improvement of D
      dimer level. Although the effects of this treatment were observed in a limited
      number of patients, our observations suggest that early coagulation disorder
      after allogeneic SCT is a strong prognostic factor for TRM, and that intervention
      with rhTM improves TRM.

PMID- 24081927
TI  - New validated multiresidue analysis of six 4-hydroxy-coumarin anticoagulant
      rodenticides in hen eggs.
AB  - Anticoagulant rodenticides are frequently a cause of poisoning of domestic
      animals, wildlife, and human beings. A toxicosis in 6,000 laying hens caused by
      the malicious addition of unknown amounts of coumatetralyl bait as well as the
      insecticides aldicarb, methomyl, and imidacloprid in the drinking water, was
      investigated in the current study. In order to determine a possible carryover of
      coumatetralyl into eggs, a rapid and reliable analytical method was developed and
      fully validated for the simultaneous detection of 6 anticoagulant rodenticides
      (warfarin, coumatetralyl, coumachlor, bromadiolone, difenacoum, and brodifacoum)
      in yolk and albumen using high-performance liquid chromatography (HPLC) with
      fluorescence detection. The method developed was reproducible, sensitive,
      accurate, and linear within the range of 0.01-1 mg/kg, which is the concentration
      range of bromadiolone and warfarin found in yolk in previously reported studies.
      The coefficient of variations of within and between days was 1.0-8.5% for yolk
      and 0.6-3.8% for albumen, while recoveries from spiked albumen and yolk samples
      were all in the range of 79-99% and 51-95%, respectively. Limits of detection in
      yolk were 0.01 mg/kg for warfarin and 0.003 mg/kg for the remaining compounds; in
      albumen, the limit of detection was 0.003 mg/kg for warfarin, coumatetralyl, and
      coumachlor, and 0.0015 mg/kg for difenacoum and brodifacoum. The application of
      the validated method revealed the presence of coumatetralyl in the yolk only at
      levels of 0.0057 mg/kg and 0.0052 mg/kg on the second and fourth day of the
      poisoning. In conclusion, the HPLC method demonstrated suitability for
      application in official analysis of anticoagulants in hen eggs.

PMID- 24081928
TI  - An outbreak of Sarcocystis calchasi encephalitis in multiple psittacine species
      within an enclosed zoological aviary.
AB  - A total of 5 psittacine birds in an enclosed zoological exhibit, including 2
      princess parrots and 3 cockatoos of 2 different species, developed severe central
      nervous system clinical signs over a 2-3-month period and died or were
      euthanized. Histologically, all birds had a lymphoplasmacytic and histiocytic
      encephalitis with intralesional protozoa consistent with a Sarcocystis species in
      addition to intramuscular tissue sarcocysts. By immunohistochemical staining,
      merozoites in brain and tissue cysts in muscle did not react with polyclonal
      antisera against Sarcocystis falcatula, Sarcocystis neurona, Toxoplasma gondii,
      and Neospora caninum, or with a monoclonal antibody to S. neurona. Transmission
      electron microscopy on sarcocyst tissue cyst walls from 2 birds was
      morphologically consistent with Sarcocystis calchasi. Polymerase chain reaction
      (PCR) amplification and sequencing of partial 18S ribosomal RNA from muscle
      tissue cysts and brain schizonts from 3 birds was consistent with a clade
      containing S. calchasi and Sarcocystis columbae but could not distinguish these
      closely related Sarcocystis species. However, PCR amplification and sequencing of
      the internal transcribed spacer 1 RNA segment in the brain from 2 birds and
      muscle from 2 birds specifically identified the isolates as S. calchasi. The
      current report documents that multiple psittacine species are susceptible
      intermediate hosts of S. calchasi, and that infection can cause encephalitis
      resulting in significant morbidity and mortality in psittacine aviaries.

PMID- 24081929
TI  - Detection and isolation of Influenza A virus subtype H1N1 from a small backyard
      swine herd in Colorado.
AB  - Influenza A virus subtype H1N1 A(H1N1)pdm09 was first confirmed in pigs in the
      United States in October 2009. In November 2010, lungs and intestines from 2 York
      piglets from a small, privately owned herd were submitted to the Colorado State
      University Veterinary Diagnostic Laboratory. The submitting veterinarian reported
      rapid weight loss and signs of pneumonia in the piglets. Gross lesions included
      caudoventral pneumonia in both piglets, and histologic lesions in the lungs
      showed characteristics consistent with influenza virus and bacterial infection.
      Ribonucleic acid extracted from fresh lung homogenates from both piglets was
      positive for influenza A(H1N1)pdm09 by a real-time reverse transcription
      polymerase chain reaction. Virus was isolated from lung homogenates from both
      piglets in Madin-Darby canine kidney cells, as well as in 10-day-old specific
      pathogen-free embryonated chicken eggs. Sequence analysis showed 98% homology
      with 2009 H1N1 human isolates from across the United States and 98% homology
      against two 2009 and 2010 swine isolates from Nebraska and Minnesota. The current
      report documents the possible transmission of pandemic influenza A(H1N1)2009
      virus [A(H1N1)pdm09] from a human being to a small, privately owned backyard
      swine herd. The owner was employed as a pharmacist, making occupational exposure
      to the pandemic influenza A(H1N1)pdm09 a possibility.

PMID- 24081930
TI  - Letter to the Editor, regarding Bluetongue virus and canine abortions.

PMID- 24081931
TI  - A survey of fish viruses isolated from wild marine fishes from the coastal waters
      of southern Korea.
AB  - A survey was conducted to investigate viral infection in 253 wild marine fishes
      harvested in the southern coastal area of Korea from 2010 to 2012. The fish that
      were captured by local anglers were randomly bought and sampled for virus
      examination. The samples were tested for presence of virus by virus isolation
      with FHM, FSP, and BF-2 cells and molecular methods (polymerase chain reaction
      and sequencing). Of the 253 fish sampled, 9 fish were infected with virus.
      Aquabirnaviruses (ABVs), Viral hemorrhagic septicemia virus (VHSV), and Red
      seabream iridovirus (RSIV) were detected in 7, 1, and 1 fish, respectively.
      Molecular phylogenies demonstrated the detected viruses (ABV, VHSV, and RSIV)
      were more closely related to viruses reported of the same type from Korea and
      Japan than from other countries, suggesting these viruses may be indigenous to
      Korean and Japanese coastal waters. 

PMID- 24081932
TI  - Pulmonary alveolar microlithiasis with concurrent pleural mesothelioma in a dog.
AB  - Pulmonary alveolar microlithiasis (PAM) is a rare pulmonary disorder
      characterized by the accumulation of calcium phosphate microliths within the
      alveoli, with only a few cases described in animals. A 10-year-old female Bulldog
      was euthanized due to history of dyspnea and recurrent pleural and pericardial
      effusions. At necropsy, numerous multifocal to coalescent protruding nodules of 1
      5 mm in diameter were scattered throughout the thoracic serosal surfaces.
      Moreover, lungs showed a diffuse pale gray color and had a generalized fine
      grainy consistency. Histological investigations revealed abundant intra-alveolar
      laminated microliths that stained positive with periodic acid-Schiff and von
      Kossa stains. The pulmonary interstitium showed multifocal, mild to moderate
      thickening, due to collagen deposition and mild hyperplasia of type 2
      pneumocytes. The pulmonary lesion was not associated with any inflammatory
      response, and mineral deposition was not observed in any other organ or tissue.
      In addition, pulmonary, pericardial, and pleural surfaces were extensively
      infiltrated by an epithelioid mesothelioma. Immunohistochemical staining revealed
      neoplastic cells that strongly coexpressed vimentin and cytokeratin, supporting
      the diagnosis of mesothelioma. An overview of PAM, including pathogenesis and
      histological characteristics, are discussed in relation to the concurrent pleural
      mesothelioma. The potential cause and effect relationship between the 2
      conditions could neither be established nor ruled out. 

PMID- 24081933
TI  - Syrian hamsters (Mesocricetus auratus) with simultaneous intestinal Giardia sp.,
      Spironucleus sp., and trichomonad infections.
AB  - A commercial facility producing hamsters with a history of infection by dwarf
      tapeworm (Hymenolepis nana) submitted 15 animals for necropsy and postmortem
      parasitological and microscopic examination. No tapeworms were detected grossly
      or microscopically. Fecal examination including gastrointestinal mucosal smears
      demonstrated mixed intestinal bacteria and low numbers of Giardia sp. Histologic
      examination of small intestine demonstrated filling of the small intestinal
      crypts by large numbers of 7-9 um * 3 um, rod to crescent or teardrop-shaped
      flagellates consistent with Spironucleus sp. These organisms had two 1-um,
      basophilic, oval nuclei and multiple superficial flagella-like structures. Much
      larger 10-15 um * 8-10 um, oval to pear-shaped organisms were also present in
      lower numbers and usually located with the crypts. These larger flagellates had
      multiple flagella and a basophilic rod-shaped nucleus. The larger flagellates
      included Giardia sp., which had an intimate interface with the surface of the
      mucosal epithelium, bilaterally symmetry, and binucleation. Lower numbers of
      trichomonads were also present and were distinguished by an undulating surface
      membrane and a single nucleus. The mucosa was hyperplastic and moderately
      inflamed. Although the tapeworm infection was resolved, diagnosis of multiple
      intestinal flagellates by fecal examination is complicated by the varying
      sensitivity and diagnostic accuracy of different types of fecal analysis for
      different flagellate types. Key differences in the morphology and location of the
      different types of flagellates as observed by histology of intestinal tissues
      provide important additional diagnostic information to distinguish trichomonads,
      Spironucleus sp., and Giardia sp. 

PMID- 24081934
TI  - Fatal outbreak of systemic pasteurellosis in a wild boar (Sus scrofa) population
      from southwest Spain.
AB  - Pasteurella multocida is a common pathogen of swine that causes specific diseases
      with great economic impact. However, the importance of this pathogen in wild boar
      is still unknown. In the current work, an outbreak of systemic pasteurellosis in
      wild boar with a high mortality rate is described. A total of 23 wild boar of all
      ages were found dead over a 5-day period on a game estate in southwest Spain
      (11.11% mortality). Three animals were necropsied and showed subcutaneous edema,
      a generalized congestion, and fibrin deposits in the peritoneal cavity.
      Hemorrhages, general congestion, and intravascular thrombosis were
      microscopically observed. Pasteurella multocida type B was isolated from all of
      the studied organs. Outbreaks of systemic pasteurellosis have been described in
      domestic pigs from Asia and Australia, but not to date in Europe. This outbreak
      suggests that systemic pasteurellosis affecting wild boar populations may be an
      important cause of mortality. 

PMID- 24081935
TI  - Molecular epidemiology of Clostridium difficile strains from nosocomial-acquired
      infections.
AB  - The purpose of this study is to analyze isolates of Clostridium difficile from
      patients with nosocomial acquired infection in respect to their molecular type
      and antimicrobial susceptibility. Fifty-nine randomly selected clinical isolates
      were characterized. Molecular typing was performed by rep-PCR (DiversiLab).
      Isolates were tested by disk diffusion towards 11 different antibiotics. All
      isolates were susceptible to metronidazole and vancomycin. Fifty five (93 %)
      isolates were resistant to erythromycin and fifty six (95 %) exhibited resistance
      to both clindamycin and moxifloxacin. Twenty rep-PCR types were identified, but
      most clinical isolates formed four major rep-PCR clusters (A1 24/59, 40 %; A2
      20/59, 33 %; A3 5/59, 8 %; A4 3/59, 5 %). These results show high genetic
      variability, which demonstrate clearly the complexity of the strains of C.
      difficile and also show an increasing rate of resistance to fluoroquinolones in
      our region emphasizing the importance of implementing surveillance programs in
      order to prevent further spread of resistance in C. difficile.

PMID- 24081936
TI  - Should low-risk patients be treated with three-dimensional conformal radiation
      therapy-accelerated partial-breast irradiation in an off-protocol setting?

PMID- 24081937
TI  - Sunitinib versus sorafenib in advanced hepatocellular cancer: results of a
      randomized phase III trial.
AB  - PURPOSE: Open-label, phase III trial evaluating whether sunitinib was superior or
      equivalent to sorafenib in hepatocellular cancer. PATIENTS AND METHODS: Patients
      were stratified and randomly assigned to receive sunitinib 37.5 mg once per day
      or sorafenib 400 mg twice per day. Primary end point was overall survival (OS).
      RESULTS: Early trial termination occurred for futility and safety reasons. A
      total of 1,074 patients were randomly assigned to the study (sunitinib arm, n =
      530; sorafenib arm, n = 544). For sunitinib and sorafenib, respectively, median
      OS was 7.9 versus 10.2 months (hazard ratio [HR], 1.30; one-sided P = .9990; two
      sided P = .0014); median progression-free survival (PFS; 3.6 v 3.0 months; HR,
      1.13; one-sided P = .8785; two-sided P = .2286) and time to progression (TTP; 4.1
      v 3.8 months; HR, 1.13; one-sided P = .8312; two-sided P = .3082) were
      comparable. Median OS was similar among Asian (7.7 v 8.8 months; HR, 1.21; one
      sided P = .9829) and hepatitis B-infected patients (7.6 v 8.0 months; HR, 1.10;
      one-sided P = .8286), but was shorter with sunitinib in hepatitis C-infected
      patients (9.2 v 17.6 months; HR, 1.52; one-sided P = .9835). Sunitinib was
      associated with more frequent and severe adverse events (AEs) than sorafenib.
      Common grade 3/4 AEs were thrombocytopenia (29.7%) and neutropenia (25.7%) for
      sunitinib; hand-foot syndrome (21.2%) for sorafenib. Discontinuations owing to
      AEs were similar (sunitinib, 13.3%; sorafenib, 12.7%). CONCLUSION: OS with
      sunitinib was not superior or equivalent but was significantly inferior to
      sorafenib. OS was comparable in Asian and hepatitis B-infected patients. OS was
      superior in hepatitis C-infected patients who received sorafenib. Sunitinib
      treated patients reported more frequent and severe toxicity.

PMID- 24081938
TI  - Statins and reduced risk of hepatocellular carcinoma in patients with hepatitis C
      virus infection: further evidence is warranted.

PMID- 24081939
TI  - Statins may protect against hepatocellular carcinoma development in patients
      infected with hepatitis C virus, but what are the mechanisms?

PMID- 24081941
TI  - Common flaws in pharmacoepidemiologic study design and analysis.

PMID- 24081940
TI  - Randomized trial to assess the impact of venlafaxine and soy protein on hot
      flashes and quality of life in men with prostate cancer.
AB  - PURPOSE: Hot flashes occur in approximately 80% of androgen-deprived men. Few
      intervention studies have been conducted to relieve hot flashes in men. PATIENTS
      AND METHODS: Eligible androgen-deprived men were randomly assigned to one of four
      daily regimens (2 * 2 factorial design) for 12 weeks: milk protein powder and
      placebo pill, venlafaxine and milk protein powder, soy protein powder and placebo
      pill, or venlafaxine and soy protein powder. The primary end point was hot flash
      symptom severity score (HFSSS), defined as number of hot flashes times severity.
      The secondary end point was quality of life (QoL), assessed by using the
      Functional Assessment of Cancer Therapy-Prostate. RESULTS: In all, 120 men age 46
      to 91 years participated. Most were white (78%) and overweight or obese (83%).
      Toxicity was minimal. Neither venlafaxine nor soy protein alone or in combination
      had a significant effect on HFSSS. Soy protein, but not venlafaxine, improved
      measures of QoL. CONCLUSION: In androgen-deprived men, neither venlafaxine nor
      soy proved effective in reducing hot flashes. Interventions that appear effective
      for decreasing hot flashes in women may not always turn out to be effective in
      men.

PMID- 24081942
TI  - External-beam accelerated partial-breast irradiation: exploring the limits of
      tolerability.

PMID- 24081943
TI  - Reply to s. Bonovas et Al, s. Clement et Al, and j.L. Lund et Al.

PMID- 24081944
TI  - Do BRCA1 and BRCA2 mutation carriers have earlier natural menopause than their
      noncarrier relatives? Results from the Kathleen Cuningham Foundation Consortium
      for Research into Familial Breast Cancer.
AB  - PURPOSE: Limited data suggest that germline BRCA1 mutations are associated with
      occult primary ovarian insufficiency and that BRCA1 and BRCA2 mutation carriers
      might have earlier natural menopause (NM) than their noncarrier relatives.
      PATIENTS AND METHODS: Eligible women were mutation carriers and noncarriers from
      families segregating a BRCA1 or BRCA2 mutation. Data were self-reported using
      uniform questionnaires at cohort entry and every 3 years thereafter. NM was
      defined as the cessation of menses for 12 months without another cause. Cox
      proportional hazards analysis modeled time from birth to NM, adjusting for
      multiple potential confounders. Analysis time was censored at the earliest of the
      following: last follow-up, bilateral oophorectomy, hysterectomy, commencement of
      hormone therapy, insertion of intrauterine device, or any cancer diagnosis.
      Hazard ratios (HRs) were estimated as a measure of how likely mutation carriers
      are, relative to noncarriers, to reach NM at a given age. RESULTS: A total of
      1,840 women were eligible for analysis. Overall only 19% reached NM. A lower
      proportion of BRCA1 and BRCA2 mutation carriers reached NM compared with
      noncarriers. Conversely, a higher proportion of mutation carriers were censored
      at cancer diagnosis or oophorectomy than noncarriers. The adjusted HR estimates
      for NM were 1.03 (95% CI, 0.75 to 1.40; P = .9) for 445 BRCA1 mutation carriers
      and 559 noncarrier relatives and 1.01 (95% CI, 0.71 to 1.42; P = .9) for 374
      BRCA2 mutation carriers and 462 noncarrier relatives. CONCLUSION: We found no
      evidence that BRCA1 and BRCA2 mutation carriers are at higher risk of NM at a
      given age than their noncarrier relatives.

PMID- 24081945
TI  - A prognostic DNA methylation signature for stage I non-small-cell lung cancer.
AB  - PURPOSE: Non-small-cell lung cancer (NSCLC) is a tumor in which only small
      improvements in clinical outcome have been achieved. The issue is critical for
      stage I patients for whom there are no available biomarkers that indicate which
      high-risk patients should receive adjuvant chemotherapy. We aimed to find DNA
      methylation markers that could be helpful in this regard. PATIENTS AND METHODS: A
      DNA methylation microarray that analyzes 450,000 CpG sites was used to study
      tumoral DNA obtained from 444 patients with NSCLC that included 237 stage I
      tumors. The prognostic DNA methylation markers were validated by a single
      methylation pyrosequencing assay in an independent cohort of 143 patients with
      stage I NSCLC. RESULTS: Unsupervised clustering of the 10,000 most variable DNA
      methylation sites in the discovery cohort identified patients with high-risk
      stage I NSCLC who had shorter relapse-free survival (RFS; hazard ratio [HR],
      2.35; 95% CI, 1.29 to 4.28; P = .004). The study in the validation cohort of the
      significant methylated sites from the discovery cohort found that
      hypermethylation of five genes was significantly associated with shorter RFS in
      stage I NSCLC: HIST1H4F, PCDHGB6, NPBWR1, ALX1, and HOXA9. A signature based on
      the number of hypermethylated events distinguished patients with high- and low
      risk stage I NSCLC (HR, 3.24; 95% CI, 1.61 to 6.54; P = .001). CONCLUSION: The
      DNA methylation signature of NSCLC affects the outcome of stage I patients, and
      it can be practically determined by user-friendly polymerase chain reaction
      assays. The analysis of the best DNA methylation biomarkers improved prognostic
      accuracy beyond standard staging.

PMID- 24081946
TI  - Randomized multicenter phase II trial comparing two schedules of etirinotecan
      pegol (NKTR-102) in women with recurrent platinum-resistant/refractory epithelial
      ovarian cancer.
AB  - PURPOSE: Etirinotecan pegol (NKTR-102) is a unique, long-acting topoisomerase-I
      inhibitor with prolonged systemic exposure to SN38 (7-ethyl-10
      hydroxycamptothecin), the active metabolite of irinotecan. This randomized phase
      II trial investigated two dosing schedules of etirinotecan pegol in patients with
      platinum-resistant/refractory ovarian carcinoma. PATIENTS AND METHODS: A total of
      71 eligible patients were randomly assigned to receive etirinotecan pegol 145
      mg/m(2) every 14 or 21 days until progression or unacceptable adverse events
      (AEs). The primary end point was objective response rate (ORR) by RECIST (version
      1.0). Secondary end points included response by Gynecologic Cancer Intergroup
      criteria, duration of ORR, progression-free survival (PFS), and overall survival
      (OS). RESULTS: The overall confirmed ORR was 20% (95% CI, 10% to 30%): 20% for
      once every 14 days, and 19% for once every 21 days. Median response duration was
      4.1 months for once every 14 days and 4.0 months for once every 21 days. Median
      PFS for every 14 and every 21 days was 4.1 and 5.3 months, respectively, and
      median OS was 10.0 and 11.7 months, respectively. Etirinotecan pegol was well
      tolerated, with the most common grade 3 to 4 AEs being dehydration (24%) and
      diarrhea (23%). Diarrhea, dehydration, nausea, and neutropenia were less frequent
      with the schedule of once every 21 days than with that of once every 14 days.
      CONCLUSION: Both schedules of etirinotecan pegol showed activity in patients with
      heavily pretreated ovarian cancer, with encouraging ORR and PFS rates. The
      schedule of once every 21 days was better tolerated and had slightly longer PFS
      and OS rates. The treatment schedule of etirinotecan pegol 145 mg/m(2) once every
      21 days was selected for the expanded phase II study and is preferred for future
      phase III studies. These findings provide support to directly compare
      etirinotecan pegol versus one of the approved drugs (eg, pegylated liposomal
      doxorubicin or topotecan) in platinum-resistant ovarian cancer.

PMID- 24081947
TI  - Aging predisposes to acute inflammatory induced pathology after tumor
      immunotherapy.
AB  - Cancer commonly occurs in the elderly and immunotherapy (IT) is being
      increasingly applied to this population. However, the majority of preclinical
      mouse tumor models assessing potential efficacy and toxicities of therapeutics
      use young mice. We assessed the impact of age on responses to systemic immune
      stimulation. In contrast to young mice, systemic cancer IT regimens or LPS given
      to aged mice resulted in rapid and lethal toxicities affecting multiple organs
      correlating with heightened proinflammatory cytokines systemically and within the
      parenchymal tissues. This inflammatory response and increased morbidity with age
      was independent of T cells or NK cells. However, prior in vivo depletion of
      macrophages in aged mice resulted in lesser cytokine levels, increased survival,
      and decreased liver histopathology. Furthermore, macrophages from aged mice and
      normal human elderly volunteers displayed heightened TNF and IL-6 production upon
      in vitro stimulation. Treatment of both TNF knockout mice and in vivo TNF
      blockade in aged mice resulted in significant increases in survival and lessened
      pathology. Importantly, TNF blockade in tumor-bearing, aged mice receiving IT
      displayed significant anti-tumor effects. These data demonstrate the critical
      role of macrophages in the age-associated hyper-inflammatory cytokine responses
      to systemic immunostimulation and underscore the importance of performing
      preclinical assessments in aged mice. 

PMID- 24081948
TI  - Aberrant ZNF423 impedes B cell differentiation and is linked to adverse outcome
      of ETV6-RUNX1 negative B precursor acute lymphoblastic leukemia.
AB  - Differentiation arrest is a hallmark of acute leukemia. Genomic alterations in B
      cell differentiation factors such as PAX5, IKZF1, and EBF-1 have been identified
      in more than half of all cases of childhood B precursor acute lymphoblastic
      leukemia (ALL). Here, we describe a perturbed epigenetic and transcriptional
      regulation of ZNF423 in ALL as a novel mechanism interfering with B cell
      differentiation. Hypomethylation of ZNF423 regulatory sequences and BMP2
      signaling result in transactivation of ZNF423alpha and a novel ZNF423beta-isoform
      encoding a nucleosome remodeling and histone deacetylase complex-interacting
      domain. Aberrant ZNF423 inhibits the transactivation of EBF-1 target genes and
      leads to B cell maturation arrest in vivo. Importantly, ZNF423 expression is
      associated with poor outcome of ETV6-RUNX1-negative B precursor ALL patients. Our
      work demonstrates that ALL is more than a genetic disease and that epigenetics
      may uncover novel mechanisms of disease with prognostic implications. 

PMID- 24081949
TI  - Neutrophil mobilization via plerixafor-mediated CXCR4 inhibition arises from lung
      demargination and blockade of neutrophil homing to the bone marrow.
AB  - Blood neutrophil homeostasis is essential for successful host defense against
      invading pathogens. Circulating neutrophil counts are positively regulated by
      CXCR2 signaling and negatively regulated by the CXCR4-CXCL12 axis. In particular,
      G-CSF, a known CXCR2 signaler, and plerixafor, a CXCR4 antagonist, have both been
      shown to correct neutropenia in human patients. G-CSF directly induces neutrophil
      mobilization from the bone marrow (BM) into the blood, but the mechanisms
      underlying plerixafor-induced neutrophilia remain poorly defined. Using a
      combination of intravital multiphoton microscopy, genetically modified mice and
      novel in vivo homing assays, we demonstrate that G-CSF and plerixafor work
      through distinct mechanisms. In contrast to G-CSF, CXCR4 inhibition via
      plerixafor does not result in neutrophil mobilization from the BM. Instead,
      plerixafor augments the frequency of circulating neutrophils through their
      release from the marginated pool present in the lung, while simultaneously
      preventing neutrophil return to the BM. Our study demonstrates for the first time
      that drastic changes in blood neutrophils can originate from alternative
      reservoirs other than the BM, while implicating a role for CXCR4-CXCL12
      interactions in regulating lung neutrophil margination. Collectively, our data
      provides valuable insights into the fundamental regulation of neutrophil
      homeostasis, which may lead to the development of improved treatment regimens for
      neutropenic patients. 

PMID- 24081951
TI  - Calcitonin gene-related peptide inhibits Langerhans cell-mediated HIV-1
      transmission.
AB  - Upon its mucosal entry, human immunodeficiency virus type 1 (HIV-1) is
      internalized by Langerhans cells (LCs) in stratified epithelia and transferred
      locally to T cells. In such epithelia, LCs are in direct contact with peripheral
      neurons secreting calcitonin gene-related peptide (CGRP). Although CGRP has
      immunomodulatory effects on LC functions, its potential influence on the
      interactions between LCs and HIV-1 is unknown. We show that CGRP acts via its
      receptor expressed by LCs and interferes with multiple steps of LC-mediated HIV-1
      transmission. CGRP increases langerin expression, decreases selected integrins,
      and activates NF-kappaB, resulting in decreased HIV-1 intracellular content,
      limited formation of LC-T cell conjugates, and elevated secretion of the CCR5
      binding chemokine CCL3/MIP-1alpha. These mechanisms cooperate to efficiently
      inhibit HIV-1 transfer from LCs to T cells and T cell infection. In vivo, HIV-1
      infection decreases CGRP plasma levels in both vaginally SHIV-challenged macaques
      and HIV-1-infected individuals. CGRP plasma levels return to baseline after
      highly active antiretroviral therapy. Our results reveal a novel path by which a
      peripheral neuropeptide acts at the molecular and cellular levels to limit
      mucosal HIV-1 transmission and suggest that CGRP receptor agonists might be used
      therapeutically against HIV-1. 

PMID- 24081950
TI  - RAGE is a nucleic acid receptor that promotes inflammatory responses to DNA.
AB  - Recognition of DNA and RNA molecules derived from pathogens or self-antigen is
      one way the mammalian immune system senses infection and tissue damage.
      Activation of immune signaling receptors by nucleic acids is controlled by
      limiting the access of DNA and RNA to intracellular receptors, but the mechanisms
      by which endosome-resident receptors encounter nucleic acids from the
      extracellular space are largely undefined. In this study, we show that the
      receptor for advanced glycation end-products (RAGE) promoted DNA uptake into
      endosomes and lowered the immune recognition threshold for the activation of Toll
      like receptor 9, the principal DNA-recognizing transmembrane signaling receptor.
      Structural analysis of RAGE-DNA complexes indicated that DNA interacted with
      dimers of the outermost RAGE extracellular domains, and could induce formation of
      higher-order receptor complexes. Furthermore, mice deficient in RAGE were unable
      to mount a typical inflammatory response to DNA in the lung, indicating that RAGE
      is important for the detection of nucleic acids in vivo. 

PMID- 24081953
TI  - Managing with pacemakers and implantable cardioverter defibrillators.

PMID- 24081954
TI  - ECG response: October 1, 2013.

PMID- 24081952
TI  - Local innervation and atrial fibrillation.

PMID- 24081955
TI  - Right heart failure secondary to compression of the right pulmonary artery by a
      large proximal aortic aneurysm.

PMID- 24081956
TI  - Echocardiographic, histopathologic, and surgical findings in Staphylococcus
      lugdunensis mitral valve endocarditis after prostate biopsy.

PMID- 24081958
TI  - Letter by Banker et al regarding article, "cardiac resynchronization therapy in
      patients with heart failure and a QRS complex <120 milliseconds: the Evaluation
      of Resynchronization Therapy for Heart Failure (LESSER-EARTH) trial".

PMID- 24081959
TI  - Letter by Dai et al regarding article, "cardiac resynchronization therapy in
      patients with heart failure and a QRS complex <120 milliseconds: the Evaluation
      of Resynchronization Therapy for Heart Failure (LESSER-EARTH) trial".

PMID- 24081960
TI  - Current opinions about coronary artery ectasia.

PMID- 24081961
TI  - National stroke registries: what can we learn from them?

PMID- 24081962
TI  - Bilirubin labeling of borderzone and anterior cerebral artery territory
      infarction.

PMID- 24081963
TI  - Predictors of recovery of responsiveness in prolonged anoxic vegetative state.

PMID- 24081964
TI  - The history of cerebral PET scanning: From physiology to cutting-edge technology.

PMID- 24081965
TI  - The history of cerebral PET scanning: From physiology to cutting-edge technology.
      Author reply.

PMID- 24081967
TI  - Pearls & oy-sters: good recovery following cerebral fat embolization with
      paroxysmal hyperactivity syndrome.

PMID- 24081968
TI  - Teaching neuroimages: reversible paradoxical lithium neurotoxicity.

PMID- 24081969
TI  - Teaching neuroimages: manganese neurotoxicity of the basal ganglia and thalamus.

PMID- 24081970
TI  - Prevalence and risk factors for pulmonary arterial hypertension in a large group
      of beta-thalassemia patients using right heart catheterization: a Webthal study.
AB  - BACKGROUND: Pulmonary arterial hypertension (PAH) remains a concern in patients
      with beta-thalassemia major (TM) and intermedia (TI); however, studies evaluating
      its prevalence and risk factors using systematic confirmation on right heart
      catheterization are lacking. METHODS AND RESULTS: This was a multicenter cross
      sectional study of 1309 Italian beta-thalassemia patients (mean age 36.4+/-9.3
      years; 46% men; 74.6% TM, 25.4% TI). Patients with a tricuspid-valve regurgitant
      jet velocity >=3.2 m/s (3.6%) on transthoracic echocardiography further underwent
      right heart catheterization to confirm the diagnosis of PAH (mean pulmonary
      arterial pressure >=25 mm Hg and pulmonary capillary wedge pressure <=15mm Hg).
      The confirmed PAH prevalence on right heart catheterization was 2.1% (95%
      confidence interval [CI], 1.4-3.0) and was higher in TI (4.8%; 95% CI, 3.0-7.7)
      than TM (1.1%; 95% CI, 0.6-2.0). The positive predictive value for the tricuspid
      valve regurgitant jet velocity >=3.2 m/s threshold for the diagnosis of pulmonary
      hypertension was 93.9%. Considerable functional limitation and decrease in the 6
      minute walk distance were noted in patients with confirmed PAH. On multivariate
      logistic regression analysis, independent risk factors for confirmed PAH were age
      (odds ratio, 1.102 per 1-year increase; 95% CI, 1.06-1.15) and splenectomy (odds
      ratio, 9.31; 95% CI, 2.57-33.7). CONCLUSIONS: The prevalence of PAH in beta
      thalassemia patients as confirmed on right heart catheterization was 2.1%, with
      an ~5-fold higher prevalence in TI than TM. Advanced age and splenectomy are risk
      factors for PAH in this patient population. CLINICAL TRIAL REGISTRATION URL:
      http://www.ClinicalTrials.gov. Unique identifier: NCT01496963.

PMID- 24081971
TI  - Long-term cardiovascular toxicity in children, adolescents, and young adults who
      receive cancer therapy: pathophysiology, course, monitoring, management,
      prevention, and research directions: a scientific statement from the American
      Heart Association.

PMID- 24081972
TI  - Management and outcomes of major bleeding during treatment with dabigatran or
      warfarin.
AB  - BACKGROUND: The aim of this study was to compare the management and prognosis of
      major bleeding in patients treated with dabigatran or warfarin. METHODS AND
      RESULTS: Two independent investigators reviewed bleeding reports from 1034
      individuals with 1121 major bleeds enrolled in 5 phase III trials comparing
      dabigatran with warfarin in 27 419 patients treated for 6 to 36 months. Patients
      with major bleeds on dabigatran (n=627 of 16 755) were older, had lower
      creatinine clearance, and more frequently used aspirin or non-steroid anti
      inflammatory agents than those on warfarin (n=407 of 10 002). The 30-day
      mortality after the first major bleed tended to be lower in the dabigatran group
      (9.1%) than in the warfarin group (13.0%; pooled odds ratio, 0.68; 95% confidence
      interval, 0.46-1.01; P=0.057). After adjustment for sex, age, weight, renal
      function, and concomitant antithrombotic therapy, the pooled odds ratio for 30
      day mortality with dabigatran versus warfarin was 0.66 (95% confidence interval,
      0.44-1.00; P=0.051). Major bleeds in dabigatran patients were more frequently
      treated with blood transfusions (423/696, 61%) than bleeds in warfarin patients
      (175/425, 42%; P<0.001) but less frequently with plasma (dabigatran, 19.8%;
      warfarin, 30.2%; P<0.001). Patients who experienced a bleed had shorter stays in
      the intensive care unit if they had previously received dabigatran (mean 1.6
      nights) compared with those who had received warfarin (mean 2.7 nights; P=0.01).
      CONCLUSIONS: Patients who experienced major bleeding on dabigatran required more
      red cell transfusions but received less plasma, required a shorter stay in
      intensive care, and had a trend to lower mortality compared with those who had
      major bleeding on warfarin. CLINICAL TRIAL REGISTRATION URL:
      http://www.ClinicalTrials.gov. Unique identifiers: NCT00262600, NCT00291330,
      NCT00680186, NCT00329238 and NCT00558259.

PMID- 24081973
TI  - Anticoagulation and survival in pulmonary arterial hypertension: results from the
      Comparative, Prospective Registry of Newly Initiated Therapies for Pulmonary
      Hypertension (COMPERA).
AB  - BACKGROUND: For almost 30 years, anticoagulation has been recommended for
      patients with idiopathic pulmonary arterial hypertension (IPAH). Supporting
      evidence, however, is limited, and it is unclear whether this recommendation is
      still justified in the modern management era and whether it should be extended to
      patients with other forms of pulmonary arterial hypertension (PAH). METHODS AND
      RESULTS: We analyzed data from Comparative, Prospective Registry of Newly
      Initiated Therapies for Pulmonary Hypertension (COMPERA), an ongoing European
      pulmonary hypertension registry. Survival rates of patients with IPAH and other
      forms of PAH were compared by the use of anticoagulation. The sample consisted of
      1283 consecutively enrolled patients with newly diagnosed PAH. Anticoagulation
      was used in 66% of 800 patients with IPAH and in 43% of 483 patients with other
      forms of PAH. In patients with IPAH, there was a significantly better 3-year
      survival (P=0.006) in patients on anticoagulation compared with patients who
      never received anticoagulation, albeit the patients in the anticoagulation group
      had more severe disease at baseline. The survival difference at 3 years remained
      statistically significant (P=0.017) in a matched-pair analysis of n=336 IPAH
      patients. The beneficial effect of anticoagulation on survival of IPAH patients
      was confirmed by Cox multivariable regression analysis (hazard ratio, 0.79; 95%
      confidence interval, 0.66-0.94). In contrast, the use of anticoagulants was not
      associated with a survival benefit in patients with other forms of PAH.
      CONCLUSIONS: The present data suggest that the use of anticoagulation is
      associated with a survival benefit in patients with IPAH, supporting current
      treatment recommendations. The evidence remains inconclusive for other forms of
      PAH. CLINICAL TRIAL REGISTRATION URL: http://www.clinicaltrials.gov. Unique
      identifier: NCT01347216.

PMID- 24081974
TI  - How children with experiences of intimate partner violence towards the mother
      understand and relate to their father.
AB  - The aim of this study was to describe how, in the aftermath of intimate partner
      violence against the mother, children understand and relate to their father. Face
      to-face interviews with four girls and four boys, aged between eight and twelve,
      were analysed using an interpretative phenomenological approach. All of the
      children had been exposed to the father's violence towards the mother. Two super
      ordinate themes were identified in the analysis: the disjunctive image of the
      father and being entangled in a conflict. The children's understanding of the
      father and their relationship with him was built on different versions of the
      father and his actions; those experienced by the child and those recounted to
      them. The situational context surrounding the described experience pervaded the
      image of the father. An ambiguity appeared to exist in the sense of different
      versions of the father and children described different emotions that could both
      hinder and elicit other feelings connected to the father. Children also conveyed
      the sense of being trapped or entangled in a conflict where their own needs and
      desires could be deemed as unsafe to express, and that they felt responsibility
      for dealing with the father's influence. 

PMID- 24081975
TI  - Vulnerability to smokeless tobacco use among those dependent on alcohol or
      illicit drugs.
AB  - INTRODUCTION: Individuals dependent on alcohol or illicit drugs are vulnerable to
      cigarette smoking and related adverse health outcomes. Less research has been
      conducted regarding whether these same groups are vulnerable to smokeless tobacco
      (ST) use. The goal of this study is to examine vulnerability to ST use among
      individuals with other drug dependence. METHODS: Utilizing the most recent (2011)
      National Survey on Drug Use and Health (NDSUH), we determined odds ratios (ORs)
      for current cigarette smoking and ST use among those with current alcohol,
      cocaine, heroin, and marijuana dependence, adjusting for relevant
      sociodemographic characteristics. Vulnerability to cigarette smoking was assessed
      to confirm that alcohol and illicit drug dependence were associated with
      increased smoking in these data sets, as shown in prior studies. Identical
      analyses were completed in the 2009 and 2010 NSDUH to assess generality. RESULTS:
      Odds for current cigarette smoking were increased for each category of dependence
      (p < .0005): alcohol (OR with 99% CI = 3.30 [2.58, 4.21]), cocaine (OR = 4.50
      [1.53, 13.20]), heroin (OR = 7.84 [1.92, 32.03]), and marijuana (OR = 3.55 [2.59,
      4.88]). Odds for current ST use were also increased among those with alcohol
      dependence (OR = 1.56 [1.06, 2.30], p = .003) but not illicit drug dependence.
      Generality of the findings was confirmed in the 2009 and 2010 NSDUH. CONCLUSIONS:
      Consistent with earlier reports, alcohol and illicit drug dependence are
      associated with robust increases in risk for cigarette smoking. In the case of
      alcohol dependence, but not illicit drug dependence, this vulnerability also
      extends to ST use.

PMID- 24081976
TI  - JAK1/2 and Pan-deacetylase inhibitor combination therapy yields improved efficacy
      in preclinical mouse models of JAK2V617F-driven disease.
AB  - PURPOSE: The myeloproliferative neoplasm myelofibrosis is characterized by
      frequent deregulation of Janus kinase (JAK)/signal transducer and activator of
      transcription (STAT) signaling, and JAK inhibitors were shown to reduce
      splenomegaly and ameliorate disease-related symptoms. However, the mutant clone
      and bone marrow fibrosis persist in the majority of patients. Using preclinical
      models, we explored whether JAK and pan-deacetylase inhibitor combination yielded
      additional benefits. EXPERIMENTAL DESIGN: The combination of the JAK1/2 inhibitor
      ruxolitinib and panobinostat was investigated using two different mouse models of
      JAK2(V617F)-driven disease. A Ba/F3 JAK2(V617F) cell-driven leukemic disease
      model was used to identify tolerated and efficacious doses. The drugs were then
      evaluated alone and in combination in a mouse model of myeloproliferative
      neoplasm-like disease based on transplantation of bone marrow transduced with a
      retrovirus expressing JAK2(V617F). Exposures were determined in blood and
      tissues, and phosphorylated STAT5 and acetylated histone H3 pharmacodynamic
      readouts were assessed in spleen and bone marrow. Histologic analysis was
      conducted on spleen and bone marrow, including staining of reticulin fibers in
      the latter organ. RESULTS: The combination of ruxolitinib and panobinostat was
      found to have a more profound effect on splenomegaly, as well as on bone marrow
      and spleen histology, compared with either agent alone, and the analysis of
      pharmacodynamic readouts showed that ruxolitinib and panobinostat have
      nonoverlapping and complementary effects. CONCLUSION: Combining JAK1/2 and pan
      deacetylase inhibitors was fairly well tolerated and resulted in improved
      efficacy in mouse models of JAK2(V617F)-driven disease compared with the single
      agents. Thus, the combination of ruxolitinib and panobinostat may represent a
      promising novel therapeutic modality for myeloproliferative neoplasms.

PMID- 24081977
TI  - Prostate cancer progression correlates with increased humoral immune response to
      a human endogenous retrovirus GAG protein.
AB  - PURPOSE: Human endogenous retroviruses (HERV) encode 8% of the human genome.
      While HERVs may play a role in autoimmune and neoplastic disease, no mechanistic
      association has yet been established. We studied the expression and
      immunogenicity of a HERV-K GAG protein encoded on chromosome 22q11.23 in relation
      to the clinical course of prostate cancer. EXPERIMENTAL DESIGN: In vitro
      expression of GAG-HERV-K was analyzed in panels of normal and malignant tissues,
      microarrays, and cell lines, and effects of demethylation and androgen
      stimulation were evaluated. Patient sera were analyzed for seroreactivity to GAG
      HERV-K and other self-antigens by ELISA and seromics (protein array profiling).
      RESULTS: GAG-HERV-K expression was most frequent in prostate tissues and
      regulated both by demethylation of the promoter region and by androgen
      stimulation. Serum screening revealed that antibodies to GAG-HERV-K are found in
      a subset of patients with prostate cancer (33 of 483, 6.8%) but rarely in male
      healthy donors (1 of 55, 1.8%). Autoantibodies to GAG-HERV-K occurred more
      frequently in patients with advanced prostate cancer (29 of 191 in stage III-IV,
      21.0%) than in early prostate cancer (4 of 292 in stages I-II, 1.4%). Presence of
      GAG-HERV-K serum antibody was correlated with worse survival of patients with
      prostate cancer, with a trend for faster biochemical recurrence in patients with
      antibodies to GAG-HERV-K. CONCLUSIONS: Preferential expression of GAG-HERV-K
      ch22q11.23 in prostate cancer tissue and increased frequency of autoantibodies
      observed in patients with advanced prostate cancer make this protein one of the
      first bona fide retroviral cancer antigens in humans, with potential as a
      biomarker for progression and biochemical recurrence rate of prostate cancer.
      Clin Cancer Res; 19(22); 6112-25. (c)2013 AACR.

PMID- 24081978
TI  - A genetically engineered oncolytic adenovirus decoys and lethally traps quiescent
      cancer stem-like cells in S/G2/M phases.
AB  - PURPOSE: Because chemoradiotherapy selectively targets proliferating cancer
      cells, quiescent cancer stem-like cells are resistant. Mobilization of the cell
      cycle in quiescent leukemia stem cells sensitizes them to cell death signals.
      However, it is unclear that mobilization of the cell cycle can eliminate
      quiescent cancer stem-like cells in solid cancers. Thus, we explored the use of a
      genetically-engineered telomerase-specific oncolytic adenovirus, OBP-301, to
      mobilize the cell cycle and kill quiescent cancer stem-like cells. EXPERIMENTAL
      DESIGN: We established CD133(+) cancer stem-like cells from human gastric cancer
      MKN45 and MKN7 cells. We investigated the efficacy of OBP-301 against quiescent
      cancer stem-like cells. We visualized the treatment dynamics of OBP-301 killing
      of quiescent cancer stem-like cells in dormant tumor spheres and xenografts using
      a fluorescent ubiquitination cell-cycle indicator (FUCCI). RESULTS: CD133(+)
      gastric cancer cells had stemness properties. OBP-301 efficiently killed CD133(+)
      cancer stem-like cells resistant to chemoradiotherapy. OBP-301 induced cell-cycle
      mobilization from G0-G1 to S/G2/M phases and subsequent cell death in quiescent
      CD133(+) cancer stem-like cells by mobilizing cell-cycle-related proteins. FUCCI
      enabled visualization of quiescent CD133(+) cancer stem-like cells and
      proliferating CD133(-) non-cancer stem-like cells. Three-dimensional
      visualization of the cell-cycle behavior in tumor spheres showed that CD133(+)
      cancer stem-like cells maintained stemness by remaining in G0-G1 phase. We showed
      that OBP-301 mobilized quiescent cancer stem-like cells in tumor spheres and
      xenografts into S/G2/M phases where they lost viability and cancer stem-like cell
      properties and became chemosensitive. CONCLUSION: Oncolytic adenoviral infection
      is an effective mechanism of cancer cell killing in solid cancer and can be a new
      therapeutic paradigm to eliminate quiescent cancer stem-like cells.

PMID- 24081979
TI  - Fleeing heat and light.

PMID- 24081980
TI  - Quantification of Na+,K+ pumps and their transport rate in skeletal muscle:
      functional significance.
AB  - During excitation, muscle cells gain Na(+) and lose K(+), leading to a rise in
      extracellular K(+) ([K(+)]o), depolarization, and loss of excitability. Recent
      studies support the idea that these events are important causes of muscle fatigue
      and that full use of the Na(+),K(+)-ATPase (also known as the Na(+),K(+) pump) is
      often essential for adequate clearance of extracellular K(+). As a result of
      their electrogenic action, Na(+),K(+) pumps also help reverse depolarization
      arising during excitation, hyperkalemia, and anoxia, or from cell damage
      resulting from exercise, rhabdomyolysis, or muscle diseases. The ability to
      evaluate Na(+),K(+)-pump function and the capacity of the Na(+),K(+) pumps to
      fill these needs require quantification of the total content of Na(+),K(+) pumps
      in skeletal muscle. Inhibition of Na(+),K(+)-pump activity, or a decrease in
      their content, reduces muscle contractility. Conversely, stimulation of the
      Na(+),K(+)-pump transport rate or increasing the content of Na(+),K(+) pumps
      enhances muscle excitability and contractility. Measurements of [(3)H]ouabain
      binding to skeletal muscle in vivo or in vitro have enabled the reproducible
      quantification of the total content of Na(+),K(+) pumps in molar units in various
      animal species, and in both healthy people and individuals with various diseases.
      In contrast, measurements of 3-O-methylfluorescein phosphatase activity
      associated with the Na(+),K(+)-ATPase may show inconsistent results. Measurements
      of Na(+) and K(+) fluxes in intact isolated muscles show that, after Na(+)
      loading or intense excitation, all the Na(+),K(+) pumps are functional, allowing
      calculation of the maximum Na(+),K(+)-pumping capacity, expressed in molar
      units/g muscle/min. The activity and content of Na(+),K(+) pumps are regulated by
      exercise, inactivity, K(+) deficiency, fasting, age, and several hormones and
      pharmaceuticals. Studies on the alpha-subunit isoforms of the Na(+),K(+)-ATPase
      have detected a relative increase in their number in response to exercise and the
      glucocorticoid dexamethasone but have not involved their quantification in molar
      units. Determination of ATPase activity in homogenates and plasma membranes
      obtained from muscle has shown ouabain-suppressible stimulatory effects of Na(+)
      and K(+). 

PMID- 24081982
TI  - Orai3 TM3 point mutation G158C alters kinetics of 2-APB-induced gating by
      disulfide bridge formation with TM2 C101.
AB  - After endoplasmic reticulum (ER) Ca(2+) store depletion, Orai channels in the
      plasma membrane (PM) are activated directly by ER-resident STIM proteins to form
      the Ca(2+)-selective Ca(2+) release-activated Ca(2+) (CRAC) channel. However, in
      the absence of Ca(2+) store depletion and STIM interaction, the mammalian
      homologue Orai3 can be activated by 2-aminoethyl diphenylborinate (2-APB),
      resulting in a nonselective cation conductance characterized by biphasic inward
      and outward rectification. Here, we use site-directed mutagenesis and patch-clamp
      analysis to better understand the mechanism by which 2-APB activates Orai3. We
      find that point mutation of glycine 158 in the third transmembrane (TM) segment
      to cysteine, but not alanine, slows the kinetics of 2-APB activation and prevents
      complete channel closure upon 2-APB washout. The "slow" phenotype exhibited by
      Orai3 mutant G158C reveals distinct open states, characterized by variable
      reversal potentials. The slow phenotype can be reversed by application of the
      reducing reagent bis(2-mercaptoethylsulfone) (BMS), but in a state-dependent
      manner, only during 2-APB activation. Moreover, the double mutant C101G/G158C, in
      which an endogenous TM2 cysteine is changed to glycine, does not exhibit altered
      kinetics of 2-APB activation. We suggest that a disulfide bridge, formed between
      the introduced cysteine at TM3 position 158 and the endogenous cysteine at TM2
      position 101, hinders transitions between Orai3 open and closed states. Our data
      provide functional confirmation of the proximity of these two residues and
      suggest a location within the Orai3 protein that is sensitive to the actions of 2
      APB. 

PMID- 24081983
TI  - Hexokinase-mitochondrial interactions regulate glucose metabolism differentially
      in adult and neonatal cardiac myocytes.
AB  - In mammalian tumor cell lines, localization of hexokinase (HK) isoforms to the
      cytoplasm or mitochondria has been shown to control their anabolic (glycogen
      synthesis) and catabolic (glycolysis) activities. In this study, we examined
      whether HK isoform differences could explain the markedly different metabolic
      profiles between normal adult and neonatal cardiac tissue. We used a set of novel
      genetically encoded optical imaging tools to track, in real-time in isolated
      adult (ARVM) and neonatal (NRVM) rat ventricular myocytes, the subcellular
      distributions of HKI and HKII, and the functional consequences on glucose
      utilization. We show that HKII, the predominant isoform in ARVM, dynamically
      translocates from mitochondria and cytoplasm in response to removal of
      extracellular glucose or addition of iodoacetate (IAA). In contrast, HKI, the
      predominant isoform in NRVM, is only bound to mitochondria and is not displaced
      by the above interventions. In ARVM, overexpression of HKI, but not HKII,
      increased glycolytic activity. In neonatal rat ventricular myocytes (NVRM),
      knockdown of HKI, but not HKII, decreased glycolytic activity. In conclusion,
      differential interactions of HKI and HKII with mitochondria underlie the
      different metabolic profiles of ARVM and NRVM, accounting for the markedly
      increased glycolytic activity of NRVM. 

PMID- 24081981
TI  - Calmodulin-dependent activation and inactivation of anoctamin calcium-gated
      chloride channels.
AB  - Calcium-dependent chloride channels serve critical functions in diverse
      biological systems. Driven by cellular calcium signals, the channels codetermine
      excitatory processes and promote solute transport. The anoctamin (ANO) family of
      membrane proteins encodes three calcium-activated chloride channels, named ANO 1
      (also TMEM16A), ANO 2 (also TMEM16B), and ANO 6 (also TMEM16F). Here we examined
      how ANO 1 and ANO 2 interact with Ca(2+)/calmodulin using nonstationary current
      analysis during channel activation. We identified a putative calmodulin-binding
      domain in the N-terminal region of the channel proteins that is involved in
      channel activation. Binding studies with peptides indicated that this domain, a
      regulatory calmodulin-binding motif (RCBM), provides two distinct modes of
      interaction with Ca(2+)/calmodulin, one at submicromolar Ca(2+) concentrations
      and one in the micromolar Ca(2+) range. Functional, structural, and
      pharmacological data support the concept that calmodulin serves as a calcium
      sensor that is stably associated with the RCBM domain and regulates the
      activation of ANO 1 and ANO 2 channels. Moreover, the predominant splice variant
      of ANO 2 in the brain exhibits Ca(2+)/calmodulin-dependent inactivation, a loss
      of channel activity within 30 s. This property may curtail ANO 2 activity during
      persistent Ca(2+) signals in neurons. Mutagenesis data indicated that the RCBM
      domain is also involved in ANO 2 inactivation, and that inactivation is
      suppressed in the retinal ANO 2 splice variant. These results advance the
      understanding of Ca(2+) regulation in anoctamin Cl(-) channels and its
      significance for the physiological function that anoctamin channels subserve in
      neurons and other cell types. 

PMID- 24081984
TI  - GCY-8, PDE-2, and NCS-1 are critical elements of the cGMP-dependent
      thermotransduction cascade in the AFD neurons responsible for C. elegans
      thermotaxis.
AB  - Certain thermoreceptor neurons are sensitive to tiny thermal fluctuations (0.01
      degrees C or less) and maintain their sensitivity across a wide range of ambient
      temperatures through a process of adaptation, but understanding of the
      biochemical basis for this performance is rudimentary. Prior studies of the AFD
      thermoreceptor in Caenorhabditis elegans revealed a signaling cascade that
      depends on a trio of receptor guanylate cyclases (rGCs), GCY-8, GCY-18, and GCY
      23, and gives rise to warming-activated thermoreceptor currents (ThRCs) carried
      by cyclic GMP-gated ion channels. The threshold for ThRC activation adapts to the
      ambient temperature through an unknown calcium-dependent process. Here, we use in
      vivo whole-cell patch-clamp recording from AFD to show that loss of GCY-8, but
      not of GCY-18 or GCY-23, reduces or eliminates ThRCs, identifying this rGC as a
      crucial signaling element. To learn more about thermotransduction and adaptation,
      we used behavioral screens and analysis of gene expression patterns to identify
      phosphodiesterases (PDEs) likely to contribute to thermotransduction. Deleting
      PDE-2 decouples the threshold for ThRC activation from ambient temperature,
      altering adaptation. We provide evidence that the conserved neuronal calcium
      sensor 1 protein also regulates the threshold for ThRC activation and propose a
      signaling network to account for ThRC activation and adaptation. Because PDEs
      play essential roles in diverse biological processes, including vertebrate
      phototransduction and olfaction, and regulation of smooth muscle contractility
      and cardiovascular function, this study has broad implications for understanding
      how extraordinary sensitivity and dynamic range is achieved in cyclic nucleotide
      based signaling networks. 

PMID- 24081987
TI  - Influence of PCR reagents on DNA polymerase extension rates measured on real-time
      PCR instruments.
AB  - BACKGROUND: Radioactive DNA polymerase activity methods are cumbersome and do not
      provide initial extension rates. A simple extension rate assay would enable study
      of basic assumptions about PCR and define the limits of rapid PCR. METHODS: A
      continuous assay that monitors DNA polymerase extension using noncovalent DNA
      dyes on common real-time PCR instruments was developed. Extension rates were
      measured in nucleotides per second per molecule of polymerase. To initiate the
      reaction, a nucleotide analog was heat activated at 95  degrees C for 5 min, the
      temperature decreased to 75  degrees C, and fluorescence monitored until
      substrate exhaustion in 30-90 min. RESULTS: The assay was linear with time for
      over 40% of the reaction and for polymerase concentrations over a 100-fold range
      (1-100 pmol/L). Extension rates decreased continuously with increasing monovalent
      cation concentrations (lithium, sodium, potassium, cesium, and ammonium). Melting
      temperature depressors had variable effects. DMSO increased rates up to 33%,
      whereas glycerol had little effect. Betaine, formamide, and 1,2-propanediol
      decreased rates with increasing concentrations. Four common noncovalent DNA dyes
      inhibited polymerase extension. Heat-activated nucleotide analogs were 92%
      activated after 5 min, and hot start DNA polymerases were 73%-90% activated after
      20 min. CONCLUSIONS: Simple DNA extension rate assays can be performed on real
      time PCR instruments. Activity is decreased by monovalent cations, DNA dyes, and
      most melting temperature depressors. Rational inclusion of PCR components on the
      basis of their effects on polymerase extension is likely to be useful in PCR,
      particularly rapid-cycle or fast PCR.

PMID- 24081985
TI  - Molecular dynamics simulations of membrane proteins under asymmetric ionic
      concentrations.
AB  - A computational method is developed to allow molecular dynamics simulations of
      biomembrane systems under realistic ionic gradients and asymmetric salt
      concentrations while maintaining the conventional periodic boundary conditions
      required to minimize finite-size effects in an all-atom explicit solvent
      representation. The method, which consists of introducing a nonperiodic energy
      step acting on the ionic species at the edge of the simulation cell, is first
      tested with illustrative applications to a simple membrane slab model and a
      phospholipid membrane bilayer. The nonperiodic energy-step method is then used to
      calculate the reversal potential of the bacterial porin OmpF, a large cation
      specific beta-barrel channel, by simulating the I-V curve under an asymmetric
      10:1 KCl concentration gradient. The calculated reversal potential of 28.6 mV is
      found to be in excellent agreement with the values of 26-27 mV measured from
      lipid bilayer experiments, thereby demonstrating that the method allows realistic
      simulations of nonequilibrium membrane transport with quantitative accuracy. As a
      final example, the pore domain of Kv1.2, a highly selective voltage-activated
      K(+) channel, is simulated in a lipid bilayer under conditions that recreate, for
      the first time, the physiological K(+) and Na(+) concentration gradients and the
      electrostatic potential difference of living cells. 

PMID- 24081988
TI  - Population differentiation of 2 forms of Bryde's whales in the Indian and Pacific
      Oceans.
AB  - Accurate identification of units for conservation is particularly challenging for
      marine species as obvious barriers to gene flow are generally lacking. Bryde's
      whales (Balaenoptera spp.) are subject to multiple human-mediated stressors,
      including fisheries bycatch, ship strikes, and scientific whaling by Japan. For
      effective management, a clear understanding of how populations of each Bryde's
      whale species/subspecies are genetically structured across their range is
      required. We conducted a population-level analysis of mtDNA control region
      sequences with 56 new samples from Oman, Maldives, and Bangladesh, plus published
      sequences from off Java and the Northwest Pacific. Nine diagnostic characters in
      the mitochondrial control region and a maximum parsimony phylogenetic analysis
      identified 2 genetically recognized subspecies of Bryde's whale: the larger,
      offshore form, Balaenoptera edeni brydei, and the smaller, coastal form,
      Balaenoptera edeni edeni. Genetic diversity and differentiation indices, combined
      with a reconstructed maximum parsimony haplotype network, indicate strong
      differences in the genetic diversity and population structure within each
      subspecies. Discrete population units are identified for B. e. brydei in the
      Maldives, Java, and the Northwest Pacific and for B. e. edeni between the
      Northern Indian Ocean (Oman and Bangladesh) and the coastal waters of Japan. 

PMID- 24081989
TI  - A monovalent anti-human CD28 domain antibody antagonist: preclinical efficacy and
      safety.
AB  - Targeting the CD28-CD80/86 pathway with an anti-CD28 antagonist is a promising
      alternative to current therapies for autoimmunity. However, attempts at
      generating conventional anti-CD28 mAbs lacking stimulatory activity has been
      challenging. In this study, we describe anti-human CD28 receptor antagonist
      domain Abs (dAbs) that are specific for human CD28. These dAbs are potent
      inhibitors of T cell activation, with an EC50 of 35 +/- 14 ng/ml for inhibition
      of proliferation. The EC50 of 53 +/- 11 ng/ml in an ex vivo CD28 receptor
      occupancy assay corresponds with in vitro functional activity, suggesting a
      direct correlation. The anti-CD28 dAb is equipotent in the inhibition of CD80-
      and CD86-mediated T cell proliferation and does not interfere with CTLA-4
      mediated downmodulation of CD86 expression on APCs. The anti-CD28 dAbs are
      monomeric and do not demonstrate any evidence of agonism or costimulatory
      activity. In cynomolgus monkeys, the anti-CD28 dAb demonstrated pharmacodynamic
      activity, as measured by the inhibition of a T cell-dependent Ab response,
      without evidence of T cell depletion or cytokine release. Furthermore, there was
      a strong correlation between systemic exposure, duration, and extent of CD28
      receptor occupancy, and pharmacodynamic activity. Taken together, these data
      support clinical evaluation of this novel anti-CD28 dAb for the treatment of
      autoimmune diseases. 

PMID- 24081990
TI  - Lipopolysaccharide stimulates platelets through an IL-1beta autocrine loop.
AB  - LPS activates platelets through TLR4, aiding productive sepsis, with stimulated
      splicing and translation of stored heteronuclear pro-IL-1beta RNA. Although the
      IL-1R type 1 (IL-1R1) receptor for IL-1 shares downstream components with the
      TLR4 receptor, platelets are not known to express IL-1R1, nor are they known to
      respond to this cytokine. We show by flow cytometry and Western blotting that
      platelets express IL-1R1, and that IL-1beta and IL-1alpha stimulate heteronuclear
      I-1beta splicing and translation of the newly made mRNA in platelets. Platelets
      also respond to the IL-1beta they make, which is exclusively associated with shed
      microparticles. Specific blockade of IL-1R1 with IL-1R antagonist suppressed
      platelet stimulation by IL-1, so IL-1beta stimulates its own synthesis in an
      autocrine signaling loop. Strikingly, IL-1R antagonist inhibition, pharmacologic
      or genetic suppression of pro-IL-1beta processing to active cytokine by caspase
      1, or blockade of de novo protein synthesis also blocked LPS-induced IL-1beta
      mRNA production. Robust stimulation of platelets by LPS therefore also required
      IL-1beta amplification. Activated platelets made IL-1beta in vivo as IL-1beta
      rapidly accumulated in occluded murine carotid arteries by posttranscriptional
      RNA splicing unique to platelets. We conclude that IL-1beta is a platelet
      agonist, that IL-1beta acts through an autocrine stimulatory loop, that an IL
      1beta autocrine loop is required to amplify platelet activation by LPS, and that
      platelets immobilized in occlusive thrombi are activated over time to produce IL
      1beta. IL-1 is a new platelet agonist that promotes its own synthesis, connecting
      thrombosis with immunity. 

PMID- 24081991
TI  - Acute Plasmodium chabaudi infection dampens humoral responses to a secondary T
      dependent antigen but enhances responses to a secondary T-independent antigen.
AB  - High rates of coinfection occur in malaria endemic regions, leading to more
      severe disease outcomes. Understanding how coinfecting pathogens influence the
      immune system is important in the development of treatment strategies that reduce
      morbidity and mortality. Using the Plasmodium chabaudi mouse model of malaria and
      immunization with model Ags that are either T-dependent (4-hydroxy-3-nitrophenyl
      [NP]-OVA) or T-independent (NP-Ficoll), we analyzed the effects of acute malaria
      on the development of humoral immunity to secondary Ags. Total Ig and IgG1 NP
      specific Ab responses to NP-OVA were significantly decreased in the P. chabaudi
      infected group compared with the uninfected group, whereas NP-specific IgG2c Ab
      was significantly increased in the P. chabaudi-infected group. In contrast,
      following injection with T-independent NP-Ficoll, the P. chabaudi-infected group
      had significantly increased NP-specific total Ig, IgM, and IgG2c Ab titers
      compared with controls. Treatment with anti-IFN-gamma led to an abrogation of the
      NP-specific IgG2c Ab induced by P. chabaudi infection but did not affect other NP
      specific Ab isotypes or titers. IFN-gamma depletion also increased the percentage
      of plasma cells in both P. chabaudi-infected and uninfected groups but decreased
      the percentage of B cells with a germinal center (GC) phenotype. Using
      immunofluorescent microscopy, we were able to detect NP(+) GCs in the spleens of
      noninfected mice, but there were no detectible NP(+) GCs in mice infected with P.
      chabaudi. These data suggest that during P. chabaudi infection, there is a shift
      toward an extrafollicular Ab response that could be responsible for decreased Ab
      responses to secondary T-dependent Ags. 

PMID- 24081993
TI  - Enhanced atherosclerosis in TIPE2-deficient mice is associated with increased
      macrophage responses to oxidized low-density lipoprotein.
AB  - Atherosclerosis has been widely recognized as an inflammatory disease of the
      arterial wall in which macrophages play a major role. Yet, how macrophage
      mediated pathology is regulated during atherosclerosis is poorly understood. TNF
      alpha-induced protein 8-like 2 (TIPE2, also known as TNFAIP8L2) is highly
      expressed in resting macrophages and can negatively regulate inflammation through
      inhibiting immune receptor signaling. We report in this article that TIPE2 plays
      a crucial atheroprotective role likely by regulating macrophage responses to
      oxidized low-density lipoprotein (ox-LDL). TIPE2-deficient macrophages treated
      with ox-LDL produced more oxidative stress and proinflammatory cytokines, and
      exhibited heightened activation of the JNK, NF-kappaB, and p38 signaling
      pathways. As a consequence, TIPE2 deficiency in bone marrow-derived cells
      exacerbated atherosclerosis development in Ldlr(-/-) mice fed a high-fat diet.
      Importantly, ox-LDL markedly downregulated TIPE2 mRNA and protein levels in
      macrophages, suggesting that ox-LDL mediates atherosclerosis by TIPE2 inhibition.
      These results indicate that TIPE2 is a new inhibitor of atherosclerosis and a
      potential drug target for treating the disease. 

PMID- 24081994
TI  - Health supervision for children with Marfan syndrome.
AB  - Marfan syndrome is a systemic, heritable connective tissue disorder that affects
      many different organ systems and is best managed by using a multidisciplinary
      approach. The guidance in this report is designed to assist the pediatrician in
      recognizing the features of Marfan syndrome as well as caring for the individual
      with this disorder. 

PMID- 24081992
TI  - Evidence for a functional thymic stromal lymphopoietin signaling axis in fibrotic
      lung disease.
AB  - Thymic stromal lymphopoietin (TSLP) recently has emerged as a key cytokine in the
      development of type 2 immune responses. Although traditionally associated with
      allergic inflammation, type 2 responses are also recognized to contribute to the
      pathogenesis of tissue fibrosis. However, the role of TSLP in the development of
      non-allergen-driven diseases, characterized by profibrotic type 2 immune
      phenotypes and excessive fibroblast activation, remains underexplored.
      Fibroblasts represent the key effector cells responsible for extracellular matrix
      production but additionally play important immunoregulatory roles, including
      choreographing immune cell recruitment through chemokine regulation. The aim of
      this study was to examine whether TSLP may be involved in the pathogenesis of a
      proto-typical fibrotic disease, idiopathic pulmonary fibrosis (IPF). We combined
      the immunohistochemical analysis of human IPF biopsy material with signaling
      studies by using cultured primary human lung fibroblasts and report for the first
      time, to our knowledge, that TSLP and its receptor (TSLPR) are highly upregulated
      in IPF. We further show that lung fibroblasts represent both a novel cellular
      source and target of TSLP and that TSLP induces fibroblast CCL2 release (via
      STAT3) and subsequent monocyte chemotaxis. These studies extend our understanding
      of TSLP as a master regulator of type 2 immune responses beyond that of allergic
      inflammatory conditions and suggest a novel role for TSLP in the context of
      chronic fibrotic lung disease. 

PMID- 24081995
TI  - Childhood interstitial lung diseases: an 18-year retrospective analysis.
AB  - OBJECTIVE: Childhood interstitial lung diseases (ILD) occur in a variety of
      clinical contexts. Advances in the understanding of disease pathogenesis and use
      of standardized terminology have facilitated increased case ascertainment.
      However, as all studies have been performed at specialized referral centers, the
      applicability of these findings to general pulmonary practice has been uncertain.
      The objective of this study was to determine the historical occurrence of
      childhood ILD to provide information reflecting general pediatric pulmonary
      practice patterns. METHODS: Childhood ILD cases seen at Vanderbilt Children's
      Hospital from 1994 to 2011 were retrospectively reviewed and classified according
      to the current pediatric diffuse lung disease histopathologic classification
      system. RESULTS: A total of 93 cases were identified, of which 91.4% were
      classifiable. A total of 68.8% (64/93) of subjects underwent lung biopsy in their
      evaluations. The largest classification categories were disorders related to
      systemic disease processes (24.7%), disorders of the immunocompromised host
      (24.7%), and disorders more prevalent in infancy (22.6%). Eight cases of
      neuroendocrine cell hyperplasia of infancy (NEHI) were identified, including 5
      that were previously unrecognized before this review. CONCLUSIONS: Our findings
      demonstrate the general scope of childhood ILD and that these cases present
      within a variety of pediatric subspecialties. Retrospective review was valuable
      in recognizing more recently described forms of childhood ILD. As a significant
      portion of cases were classifiable based on clinical, genetic, and/or
      radiographic criteria, we urge greater consideration to noninvasive diagnostic
      approaches and suggest modification to the current childhood ILD classification
      scheme to accommodate the increasing number of cases diagnosed without lung
      biopsy.

PMID- 24081996
TI  - International reach of tobacco marketing among young children.
AB  - BACKGROUND: Prosmoking messages, delivered through marketing and the media, can
      reach very young children and influence attitudes and behaviors around smoking.
      This study examined the reach of tobacco marketing to 5 and 6 year olds in 6 low-
      and middle-income countries. METHODS: Researchers worked one-on-one with 5 and 6
      year olds in Brazil, China, India, Nigeria, Pakistan, and Russia (N = 2423). The
      children were asked to match logos with pictures of products, including 8 logos
      for cigarette brands. Analyses examined, overall and by country, whether gender,
      age, location, household use of tobacco, and knowledge of media characters were
      associated with awareness of cigarette brand logos. Additional analyses
      considered the relationship between cigarette brand logo awareness and intentions
      to smoke. RESULTS: Overall, 68% of 5 and 6 year olds could identify at least 1
      cigarette brand logo, ranging from 50% in Russia to 86% in China. Across
      countries, being slightly older and having someone in the household who used
      tobacco, were significantly associated with greater odds of being able to
      identify at least 1 cigarette brand logo. CONCLUSIONS: The majority of young
      children from low- and middle-income countries are familiar with cigarette
      brands. This study's findings suggest that more effective measures are needed to
      restrict the reach of tobacco marketing.

PMID- 24081997
TI  - Guiding principles for pediatric hospital medicine programs.
AB  - Pediatric hospital medicine programs have an established place in pediatric
      medicine. This statement speaks to the expanded roles and responsibilities of
      pediatric hospitalists and their integrated role among the community of
      pediatricians who care for children within and outside of the hospital setting. 

PMID- 24081998
TI  - Enhancing pediatric workforce diversity and providing culturally effective
      pediatric care: implications for practice, education, and policy making.
AB  - This policy statement serves to combine and update 2 previously independent but
      overlapping statements from the American Academy of Pediatrics (AAP) on
      culturally effective health care (CEHC) and workforce diversity. The AAP has long
      recognized that with the ever-increasing diversity of the pediatric population in
      the United States, the health of all children depends on the ability of all
      pediatricians to practice culturally effective care. CEHC can be defined as the
      delivery of care within the context of appropriate physician knowledge,
      understanding, and appreciation of all cultural distinctions, leading to optimal
      health outcomes. The AAP believes that CEHC is a critical social value and that
      the knowledge and skills necessary for providing CEHC can be taught and acquired
      through focused curricula across the spectrum of lifelong learning. This
      statement also addresses workforce diversity, health disparities, and affirmative
      action. The discussion of diversity is broadened to include not only race,
      ethnicity, and language but also cultural attributes such as gender, religious
      beliefs, sexual orientation, and disability, which may affect the quality of
      health care. The AAP believes that efforts must be supported through health
      policy and advocacy initiatives to promote the delivery of CEHC and to overcome
      educational, organizational, and other barriers to improving workforce diversity.

PMID- 24081999
TI  - ED utilization trends in sports-related traumatic brain injury.
AB  - BACKGROUND: Emergency department (ED) visits for sports-related traumatic brain
      injuries (TBIs) have risen. This study evaluated how the number and severity of
      admissions have changed as ED visits for sports-related TBIs have increased.
      METHODS: A retrospective study of children aged 0 to 19 years at a level 1 trauma
      center was performed. Patients from 2002 to 2011 with a primary or secondary
      diagnosis of TBI were identified from the hospital's inpatient and outpatient
      trauma registries. Frequencies were used to characterize the population, chi(2)
      analysis was performed to determine differences between groups, and regression
      analysis looked at relationship between year and injury severity score or length
      of stay. RESULTS: Sport was responsible for injury in 3878 (15.4%) cases during
      the study period; 3506 (90.4%) were discharged from the hospital, and 372 (9.6%)
      were admitted. Seventy-three percent were male patients and 78% Caucasian; mean
      age was 13 +/- 3.5 years. ED visits for sports-related TBIs increased 92% over
      the study period, yet there was no significant change (chi(2) = 9.8, df = 9, P =
      .37) in the percentage of children admitted. Mean injury severity score for those
      admitted decreased from 7.8 to 4.8 (beta = -0.46; P = .006); length of stay
      trended downward (beta = -0.05; P = .05). CONCLUSIONS: The percentage of children
      being admitted from the ED with sports-related TBI has not changed over the past
      10 years. The severity of admitted sports-related TBI is decreasing. Additional
      research is needed to correlate these trends with other TBI mechanisms.

PMID- 24082000
TI  - Nonmedical vaccine exemptions and pertussis in California, 2010.
AB  - BACKGROUND: In 2010, 9120 cases of pertussis were reported in California, more
      than any year since 1947. Although this resurgence has been widely attributed to
      waning immunity of the acellular vaccine, the role of vaccine refusal has not
      been explored in the published literature. Many factors likely contributed to the
      outbreak, including the cyclical nature of pertussis, improved diagnosis, and
      waning immunity; however, it is important to understand if clustering of
      unvaccinated individuals also played a role. METHODS: We analyzed nonmedical
      exemptions (NMEs) for children entering kindergarten from 2005 through 2010 and
      pertussis cases with onset in 2010 in California to determine if NMEs increased
      in that period, if children obtaining NMEs clustered spatially, if pertussis
      cases clustered spatially and temporally, and if there was statistically
      significant overlap between clusters of NMEs and cases. RESULTS: Kulldorff's scan
      statistics identified 39 statistically significant clusters of high NME rates and
      2 statistically significant clusters of pertussis cases in this time period.
      Census tracts within an exemptions cluster were 2.5 times more likely to be in a
      pertussis cluster (odds ratio = 2.47, 95% confidence interval: 2.22-2.75). More
      cases occurred within as compared with outside exemptions clusters (incident rate
      ratios = 1.20, 95% confidence interval: 1.10-1.30). The association remained
      significant after adjustment for demographic factors. NMEs clustered spatially
      and were associated with clusters of pertussis cases. CONCLUSIONS: Our data
      suggest clustering of NMEs may have been 1 of several factors in the 2010
      California pertussis resurgence.

PMID- 24082001
TI  - Early intervention, IDEA Part C services, and the medical home: collaboration for
      best practice and best outcomes.
AB  - The medical home and the Individuals With Disabilities Education Act Part C Early
      Intervention Program share many common purposes for infants and children ages 0
      to 3 years, not the least of which is a family-centered focus. Professionals in
      pediatric medical home practices see substantial numbers of infants and toddlers
      with developmental delays and/or complex chronic conditions. Economic, health,
      and family-focused data each underscore the critical role of timely referral for
      relationship-based, individualized, accessible early intervention services and
      the need for collaborative partnerships in care. The medical home process and
      Individuals With Disabilities Education Act Part C policy both support nurturing
      relationships and family-centered care; both offer clear value in terms of
      economic and health outcomes. Best practice models for early intervention
      services incorporate learning in the natural environment and coaching models.
      Proactive medical homes provide strategies for effective developmental
      surveillance, family-centered resources, and tools to support high-risk groups,
      and comanagement of infants with special health care needs, including the
      monitoring of services provided and outcomes achieved. 

PMID- 24082002
TI  - National trends in psychotropic medication use in young children: 1994-2009.
AB  - OBJECTIVE: To examine recent national trends in psychotropic use for very young
      children at US outpatient medical visits. METHODS: Data for 2- to 5-year-old
      children (N = 43 598) from the 1994-2009 National Ambulatory and National
      Hospital Ambulatory Medical Care Surveys were used to estimate the weighted
      percentage of visits with psychotropic prescriptions. Multivariable logistic
      regression was used to identify factors associated with psychotropic use. Time
      effects were examined in 4-year blocks (1994-1997, 1998-2001, 2002-2005, and 2006
      2009). RESULTS: Psychotropic prescription rates were 0.98% from 1994-1997, 0.83%
      from 1998-2001, 1.45% from 2002-2005, and 1.00% from 2006-2009. The likelihood of
      preschool psychotropic use was highest in 2002-2005 (1994-1997 adjusted odds
      ratio [AOR] versus 2002-2005: 0.67; 1998-2001 AOR versus 2002-2005: 0.63; 2006
      2009 AOR versus 2002-2005: 0.64), then diminished such that the 2006-2009
      probability of use did not differ from 1994-1997 or from 1998-2001. Boys (AOR
      versus girls: 1.64), white children (AOR versus other race: 1.42), older children
      (AOR for 4 to 5 vs 2 to 3 year olds: 3.87), and those lacking private insurance
      (AOR versus privately insured: 2.38) were more likely than children from other
      groups to receive psychotropic prescriptions. CONCLUSIONS: Psychotropic
      prescription was notable for peak usage in 2002-2005 and sociodemographic
      disparities in use. Further study is needed to discern why psychotropic use in
      very young children stabilized in 2006-2009, as well as reasons for increased use
      in boys, white children, and those lacking private health insurance.

PMID- 24082003
TI  - Late-preterm birth and lifetime socioeconomic attainments: the Helsinki birth
      cohort study.
AB  - OBJECTIVE: We examined if those born late-preterm (at 34 to 36 weeks of
      gestation) differed from those born at term in their maximum attained lifetime
      socioeconomic position (SEP) across the adult years up to 56 to 66 years, and in
      intergenerational social mobility from childhood parental SEP to own attained
      SEP. METHODS: Participants were 8993 Finnish men and women of the Helsinki Birth
      Cohort Study born between 1934 and 1944. Gestational age was extracted from
      hospital birth records and socioeconomic attainments from Finnish National
      Census. RESULTS: Compared with those born at term, those born late-preterm were
      more likely to be manual workers, have a basic or upper secondary level of
      education, belong to the lowest third based on their incomes, and less likely to
      belong to the highest third based on their incomes. Late-preterm individuals were
      also less likely to be upwardly mobile and more likely to be downwardly mobile;
      they were less likely to have higher occupations and more likely to have lower
      occupations than their fathers. They were also less likely to be upwardly mobile
      if incomes were used as the outcome of own attained SEP, and men were more likely
      to be downwardly mobile if education was used as the outcome of own attained SEP.
      CONCLUSIONS: This study demonstrates that there are considerable long-term
      socioeconomic disadvantages associated with late-preterm birth, which are not
      explained by the parent-of-origin SEP.

PMID- 24082004
TI  - A Bayesian adaptive Phase I-II clinical trial for evaluating efficacy and
      toxicity with delayed outcomes.
AB  - BACKGROUND: In traditional Phase-I oncology trials, the safety of a new
      chemotherapeutic agent is tested in a dose escalation study to identify the
      maximum tolerated dose, which is defined as the highest dose with acceptable
      toxicity. An alternate approach is to jointly model toxicity and efficacy and
      allow dose finding to be directed by a prespecified trade-off between efficacy
      and toxicity. With this goal in mind, several designs have been proposed to
      jointly model toxicity and efficacy in a Phase I-II dose escalation study. A
      factor limiting the use of these designs is that toxicity and efficacy must be
      observed in a timely manner. PURPOSE: One approach to overcoming this problem is
      to model toxicity and efficacy as time-to-event outcomes. This would allow new
      subjects to be enrolled before full information is available for previous
      subjects while incorporating partial information when adaptively assigning new
      subjects to a dose level. METHODS: We propose a Phase I-II dose escalation study
      for evaluating toxicity and efficacy with delayed outcomes by jointly modeling
      toxicity and efficacy as time-to-event outcomes. We apply our proposed design to
      a Phase I-II clinical trial of a novel targeted toxin for canine hemangiosarcoma.
      RESULTS: Our simulation results show that our design identifies the optimal dose
      at a similar rate to dose finding that treats toxicity and efficacy as binary
      outcomes, but with substantial savings in study duration. LIMITATIONS: Our
      proposed design has acceptable operating characteristics and dramatically reduces
      the trial duration compared to a design that considers toxicity and efficacy as
      binary outcomes, but comes at the cost of enrolling additional subjects when all
      dose levels are unacceptable. CONCLUSIONS: We developed a novel Phase I-II design
      that accounts for delayed outcomes by modeling toxicity and efficacy as time-to
      event outcomes. Our design has similar operating characteristics to
      efficacy/toxicity trade-off designs that consider efficacy and toxicity as binary
      outcomes, but with a dramatically shorter study duration.

PMID- 24082005
TI  - Reappraisal of short-term low-volume hydration in cisplatin-based chemotherapy:
      results of a prospective feasibility study in advanced lung cancer in the Okayama
      Lung Cancer Study Group Trial 1002.
AB  - OBJECTIVE: Cisplatin can induce severe renal toxicity. However, the degree and
      pattern of hydration that is most efficient at preventing it have scarcely been
      formally evaluated. We here performed a prospective feasibility study of
      cisplatin-based chemotherapy with short-term low-volume hydration in advanced
      lung cancer. METHODS: Chemo-naive patients with advanced lung cancer and
      reserving renal function who were suitable for cisplatin use (>=60 mg/m(2) on Day
      1) were eligible for this study. Two-and-a-half-liter hydration within ~4.5 h was
      investigated. The primary end point was the proportion of patients who underwent
      cisplatin-based chemotherapy without any Grade 2 or more renal toxicity in the
      first cycle. RESULTS: A total of 46 patients were registered, all of whom were
      evaluable for renal toxicity. The median baseline creatinine score was 0.70 mg/dl
      and the median cisplatin dose on Day 1 was 80 mg/m(2). In the first cycle, none
      of the patients developed Grade 2 or more creatinine toxicity, which met the
      primary endpoint. Four patients (9%) had Grade 1 toxicity, with a median worst
      creatinine score of 1.19 mg/dl, but it disappeared rapidly. Creatinine toxicity
      was influenced by several clinical factors, including the performance status. Ten
      patients (22%) needed extra hydration during the first cycle, mainly due to
      gastrointestinal toxicity. However, all 10 were able to undergo further cycles of
      treatment. Thirty-two (86%) of the 37 patients who were assumed to be able to
      undergo further treatment at our institute received it in an outpatient setting.
      CONCLUSIONS: This study demonstrated prospectively the feasibility of short-term
      low-volume hydration.

PMID- 24082006
TI  - Rye flour enriched with arabinoxylans in rye bread making.
AB  - The aim of the study was to investigate physical and chemical properties of
      preparations of water soluble arabinoxylans (arabinoxylan-enriched flour)
      obtained by industrial method and their derivatives (obtained by hydrolysis and
      cross-linking of aranbinoxylans), as well as their impact on baking properties of
      rye flours. Additionally, these results were compared with highly purified
      arabinoxylans prepared by laboratory method and well characterized in the
      literature. Flour enriched with arabinoxylans was obtained by industrial method
      involving air separation of flour particles. It was characterized by 8.6%
      arabinoxylan content, lack of insoluble material and substantial residue (67%) of
      starch and dextrins. The addition of all industrial method preparations in amount
      of 10% (i.e. approx. 1% water soluble arabinoxylans), to rye flours resulted in
      an increase in water absorption, bread volume and decrease in hardness of the
      bread crumb and the effect was especially strong in the case of flour type 720.
      Due to the easiness of isolation procedure, industrial method preparation could
      be advised as an improver for rye bread making. 

PMID- 24082007
TI  - The centennial of vitamin A: a century of research in retinoids and carotenoids.

PMID- 24082008
TI  - Letters to the editor: Load bearing in the equine metacarpal.

PMID- 24082009
TI  - The more the merrier: recent hybridization and polyploidy in cardamine.
AB  - This article describes the use of cytogenomic and molecular approaches to explore
      the origin and evolution of Cardamine schulzii, a textbook example of a recent
      allopolyploid, in its ~110-year history of human-induced hybridization and
      allopolyploidy in the Swiss Alps. Triploids are typically viewed as bridges
      between diploids and tetraploids but rarely as parental genomes of high-level
      hybrids and polyploids. The genome of the triploid semifertile hybrid Cardamine *
      insueta (2n = 24, RRA) was shown to combine the parental genomes of two diploid
      (2n = 2x = 16) species, Cardamine amara (AA) and Cardamine rivularis (RR). These
      parental genomes have remained structurally stable within the triploid genome
      over the >100 years since its origin. Furthermore, we provide compelling evidence
      that the alleged recent polyploid C. schulzii is not an autohexaploid derivative
      of C. * insueta. Instead, at least two hybridization events involving C. *
      insueta and the hypotetraploid Cardamine pratensis (PPPP, 2n = 4x-2 = 30) have
      resulted in the origin of the trigenomic hypopentaploid (2n = 5x-2 = 38, PPRRA)
      and hypohexaploid (2n = 6x-2 = 46, PPPPRA). These data show that the semifertile
      triploid hybrid can promote a merger of three different genomes and demonstrate
      how important it is to reexamine the routinely repeated textbook examples using
      modern techniques.

PMID- 24082011
TI  - The C2H2 transcription factor regulator of symbiosome differentiation represses
      transcription of the secretory pathway gene VAMP721a and promotes symbiosome
      development in Medicago truncatula.
AB  - Transcription factors (TFs) are thought to regulate many aspects of nodule and
      symbiosis development in legumes, although few TFs have been characterized
      functionally. Here, we describe regulator of symbiosome differentiation (RSD) of
      Medicago truncatula, a member of the Cysteine-2/Histidine-2 (C2H2) family of
      plant TFs that is required for normal symbiosome differentiation during nodule
      development. RSD is expressed in a nodule-specific manner, with maximal
      transcript levels in the bacterial invasion zone. A tobacco (Nicotiana tabacum)
      retrotransposon (Tnt1) insertion rsd mutant produced nodules that were unable to
      fix nitrogen and that contained incompletely differentiated symbiosomes and
      bacteroids. RSD protein was localized to the nucleus, consistent with a role of
      the protein in transcriptional regulation. RSD acted as a transcriptional
      repressor in a heterologous yeast assay. Transcriptome analysis of an rsd mutant
      identified 11 genes as potential targets of RSD repression. RSD interacted
      physically with the promoter of one of these genes, VAMP721a, which encodes
      vesicle-associated membrane protein 721a. Thus, RSD may influence symbiosome
      development in part by repressing transcription of VAMP721a and modifying vesicle
      trafficking in nodule cells. This establishes RSD as a TF implicated directly in
      symbiosome and bacteroid differentiation and a transcriptional regulator of
      secretory pathway genes in plants.

PMID- 24082012
TI  - Differential role of all-trans retinoic acid in promoting the development of CD4+
      and CD8+ regulatory T cells.
AB  - It is known that ATRA promotes the development of TGF-beta-induced CD4(+)Foxp3(+)
      iTregs, which play a vital role in the prevention of autoimmune diseases;
      however, the role of ATRA in facilitating the differentiation and function of
      CD8(+)Foxp3(+) iTregs remains elusive. Using a head-to-head comparison, we found
      that ATRA promoted expression of Foxp3 and development of CD4(+) iTregs, but it
      did not promote Foxp3 expression on CD8(+) cells. Using a standard in vitro
      assay, we demonstrated that CD8(+) iTregs induced by TGF-beta and ATRA were not
      superior to CD8(+) iTregs induced by TGF-beta alone. In cGVHD, in a typical lupus
      syndrome model where DBA2 spleen cells were transferred to DBA2xC57BL/6 F1 mice,
      we observed that both CD8(+) iTregs induced by TGF-beta and ATRA and those
      induced by TGF-beta alone had similar therapeutic effects. ATRA did not boost
      but, conversely, impaired the differentiation and function of human CD8(+)
      iTregs. CD8(+) cells expressed the ATRA receptor RAR and responded to ATRA,
      similar to CD4(+) cells. We have identified the differential role of ATRA in
      promoting Foxp3(+) Tregs in CD4(+) and CD8(+) cell populations. These results
      will help to determine a protocol for developing different Treg cell populations
      and may provide novel insights into clinical cell therapy for patients with
      autoimmune diseases and those needing organ transplantation. 

PMID- 24082014
TI  - Acute pleural effusion from aortic aneurysm rupture.

PMID- 24082016
TI  - Global goal for maternal health unlikely to be achieved.

PMID- 24082013
TI  - CD8+ dendritic cell-mediated tolerance of autoreactive CD4+ T cells is deficient
      in NOD mice and can be corrected by blocking CD40L.
AB  - DCs are important mediators of peripheral tolerance for the prevention of
      autoimmunity. Chimeric alphaDEC-205 antibodies with attached antigens allow in
      vivo antigen-specific stimulation of T cells by CD8(+) DCs, resulting in
      tolerance in nonautoimmune mice. However, it is not clear whether DC-mediated
      tolerance induction occurs in the context of ongoing autoimmunity. We assessed
      the role of CD8(+) DCs in stimulation of autoreactive CD4(+) T cells in the NOD
      mouse model of type 1 diabetes. Targeting of antigen to CD8(+) DCs via alphaDEC
      205 led to proliferation and expansion of beta-cell specific BDC2.5 T cells.
      These T cells also produced IL-2 and IFN-gamma and did not up-regulate FoxP3,
      consistent with an activated rather than tolerant phenotype. Similarly,
      endogenous BDC peptide-reactive T cells, identified with I-A(g7) tetramers, did
      not become tolerant after antigen delivery via alphaDEC-205: no deletion or Treg
      induction was observed. We observed that CD8(+) DCs from NOD mice expressed
      higher surface levels of CD40 than CD8(+) DCs from C57BL/6 mice. Blockade of CD40
      CD40L interactions reduced the number of BDC2.5 T cells remaining in mice, 10
      days after antigen targeting to CD8 DCs, and blocked IFN-gamma production by
      BDC2.5 T cells. These data indicate that the ability of autoreactive CD4(+) T
      cells to undergo tolerance mediated by CD8(+) DCs is defective in NOD mice and
      that blocking CD40-CD40L interactions can restore tolerance induction. 

PMID- 24082017
TI  - New WHO guidelines on intimate-partner violence.

PMID- 24082019
TI  - Doctors among early adopters of Google Glass.

PMID- 24082018
TI  - Influence of retirement on nonadherence to medication for hypertension and
      diabetes.
AB  - BACKGROUND: The extent to which common life transitions influence medication
      adherence among patients remains unknown. We examined whether retirement is
      associated with a change in adherence to medication in patients with hypertension
      or type 2 diabetes. METHODS: Participants in the Finnish Public Sector study were
      linked to national registers. We included data for the years 1994-2011. We
      identified and followed 3468 adult patients with hypertension and 412 adult
      patients with type 2 diabetes for medication adherence for the 3 years before
      their retirement and the 4 years after their retirement (mean follow-up 6.8 yr).
      Our primary outcome was proportion of patients with poor adherence to medication,
      which we defined as less than 40% of days covered by treatment. We determined
      these proportions before and after retirement using data from filled
      prescriptions. RESULTS: The preretirement prevalence of poor adherence to
      medication was 6% in men and women with hypertension, 2% in men with diabetes and
      4% in women with diabetes. Among men, retirement was associated with an increased
      risk of poor adherence to both antihypertensive agents (odds ratio [OR] 1.32, 95%
      confidence interval [CI] 1.03-1.68) and antidiabetic drugs (OR 2.40, 95% CI 1.37
      4.20). Among women, an increased risk of poor adherence was seen only for
      antihypertensive agents (OR 1.25, 95% CI 1.07-1.46). Similar results were
      apparent for alternative definitions of poor adherence. Our results did not
      differ across strata of age, socioeconomic status or comorbidity. INTERPRETATION:
      We found a decline in adherence to medication after retirement among men and
      women with hypertension and men with type 2 diabetes. If these findings can be
      confirmed, we need randomized controlled trials to determine whether
      interventions to reduce poor adherence after retirement could improve clinical
      outcomes of treatments for hypertension and diabetes.

PMID- 24082020
TI  - Canada's physician supply at an all-time high.

PMID- 24082021
TI  - Mount Pleasant Village: planned for public health.

PMID- 24082022
TI  - Trends in 1-year survival of people admitted to hospital in Ontario, 1994-2009.
AB  - BACKGROUND: Changes in the long-term survival of people admitted to hospital is
      unknown. This study examined trends in 1-year survival of patients admitted to
      hospital adjusted for improved survival in the general population. METHODS: One
      year survival after admission to hospital was determined for all adults admitted
      to hospital in Ontario in 1994, 1999, 2004, or 2009 by linking to vital
      statistics datasets. Annual survival in the general population was determined
      from life tables for Ontario. RESULTS: Between 1994 and 2009, hospital use
      decreased (from 8.8% to 6.3% of the general adult population per year), whereas
      crude 1-year mortality among people with hospital admissions increased (from 9.2%
      to 11.6%). During this time, patients in hospital became significantly older
      (median age increased from 51 to 58 yr) and sicker (the proportion with a
      Charlson comorbidity index score of 0 decreased from 68.2% to 60.0%), and were
      more acutely ill on admission (elective admissions decreased from 47.4% to 42.0%;
      proportion brought to hospital by ambulance increased from 16.1% to 24.8%).
      Compared with 1994, the adjusted odds ratio (OR) for death at 1 year in 2009 was
      0.78 (95% confidence interval [CI] 0.77-0.79). However, 1-year risk of death in
      the general population decreased by 24% during the same time. After adjusting for
      improved survival in the general population, risk of death at 1 year for people
      admitted to hospital remained significantly lower in 2009 than in 1994 (adjusted
      relative excess risk 0.81, 95% CI 0.80-0.82). INTERPRETATION: After accounting
      for both the increased burden of patient sickness and improved survival in the
      general population, 1-year survival for people admitted to hospital increased
      significantly from 1994 to 2009. The reasons for this improvement cannot be
      determined from these data.

PMID- 24082023
TI  - A Canadian screening program for hepatitis C: is now the time?

PMID- 24082024
TI  - Physician pay should reflect workloads, say economists.

PMID- 24082025
TI  - Advocacy as medical responsibility.

PMID- 24082026
TI  - Facebook Advertisements for Inexpensive Participant Recruitment Among Women in
      Early Pregnancy.
AB  - Facebook advertisements were used to recruit nulliparous women in the first 20
      weeks of pregnancy for an online survey about their childbirth preferences. A
      campaign of ads was targeted to women, aged 18 to 44 years, residing in the
      United States. The ads were viewed 10,577,381 times by 7,248,985 unique Facebook
      users over 18 weeks in 2011. The ad campaign yielded 6,094 clicks by 5,963 unique
      users at a mean cost of $0.63 per click and a unique click-through rate of 0.08%.
      Of those who clicked through to the study site, 18% (n = 1,075) consented to
      participate. The participant pool was reduced to 344 women after application of
      strict eligibility criteria. Participants represented 43 states and the District
      of Columbia, their mean age was 20.9 years (Mdn = 19.0, SD = 4.0), and their mean
      weeks' gestation was 11.5 (SD = 5.8). The campaign cost was $3,821.81 or $11.11
      per eligible participant. 

PMID- 24082027
TI  - Information processing versus social cognitive mediators of weight loss in a
      podcast-delivered health intervention.
AB  - Podcasting is an emerging technology, and previous interventions have shown
      promising results using theory-based podcast for weight loss among overweight and
      obese individuals. This study investigated whether constructs of social cognitive
      theory and information processing theories (IPTs) mediate the effect of a podcast
      intervention on weight loss among overweight individuals. Data are from Pounds
      off Digitally, a study testing the efficacy of two weight loss podcast
      interventions (control podcast and theory-based podcast). Path models were
      constructed (n = 66). The IPTs, elaboration likelihood model, information control
      theory, and cognitive load theory mediated the effect of a theory-based podcast
      on weight loss. The intervention was significantly associated with all IPTs.
      Information control theory and cognitive load theory were related to elaboration,
      and elaboration was associated with weight loss. Social cognitive theory
      constructs did not mediate weight loss. Future podcast interventions grounded in
      theory may be effective in promoting weight loss. 

PMID- 24082030
TI  - Inhibitory effects of spirulina platensis on carcinogen-activating cytochrome
      P450 isozymes and potential for drug interactions.
AB  - Spirulina platensis (SP) has been considered as potential food source of 21st
      century due to its remarkable nutrient profile and therapeutic benefits. However,
      the cytochrome P450 (CYP)-mediated drug/chemical interaction potential of SP has
      not yet been pursued. We investigated the effects of SP on the expressions and
      enzymatic activities of main CYP isozymes. After the rats were orally
      administered with SP daily for 5 consecutive weeks, there were significant
      downregulations in hepatic expression levels and inhibition in enzymatic
      activities of CYP1A2 and CYP2E1 compared to controls. In addition, a significant
      decrease was observed in CYP2C6-associated enzyme activity with no remarkable
      changes in messenger RNA (mRNA)/protein levels. The SP application resulted in
      significant increases in mRNA/protein levels of both CYP2B1 and CYP3A1 without a
      significant change in enzyme activities. These findings partly explain the
      chemopreventive properties of SP toward various organ toxicities, mutagenesis,
      and carcinogenesis; however, its coadministration with some CYP substrates may
      lead to undesirable drug interactions. 

PMID- 24082028
TI  - Analyses of Ca2+ accumulation and dynamics in the endoplasmic reticulum of
      Arabidopsis root cells using a genetically encoded Cameleon sensor.
AB  - In planta, very limited information is available about how the endoplasmic
      reticulum (ER) contributes to cellular Ca(2+) dynamics and homeostasis. Here, we
      report the generation of an ER-targeted Cameleon reporter protein suitable for
      analysis of Ca(2+) accumulation and dynamics in the lumen of the ER in plant
      cells. Using stably transformed Arabidopsis (Arabidopsis thaliana) plants
      expressing this reporter protein, we observed a transiently enhanced accumulation
      of Ca(2+) in the ER in response to stimuli inducing cytosolic Ca(2+) rises in
      root tip cells. In all experimental conditions, ER Ca(2+) dynamics were
      substantially different from those monitored in the cytosol. A pharmacological
      approach enabled us to evaluate the contribution of the different ER-resident
      Ca(2+)-ATPase classes in the regulation of the ER Ca(2+) homeostasis. Taken
      together, our results do not provide evidence for a role of the ER as a major
      source that releases Ca(2+) for stimulus-induced increases in cytosolic Ca(2+)
      concentration. Instead, our results show that the luminal ER Ca(2+) elevations
      typically follow cytosolic ones, but with distinct dynamics. These findings
      suggest fundamental differences for the function of the ER in cellular Ca(2+)
      homeostasis in plants and animals. 

PMID- 24082029
TI  - The nodulation factor hydrolase of Medicago truncatula: characterization of an
      enzyme specifically cleaving rhizobial nodulation signals.
AB  - Nodule formation induced by nitrogen-fixing rhizobia depends on bacterial
      nodulation factors (NFs), modified chitin oligosaccharides with a fatty acid
      moiety. Certain NFs can be cleaved and inactivated by plant chitinases. However,
      the most abundant NF of Sinorhizobium meliloti, an O-acetylated and sulfated
      tetramer, is resistant to hydrolysis by all plant chitinases tested so far.
      Nevertheless, this NF is rapidly degraded in the host rhizosphere. Here, we
      identify and characterize MtNFH1 (for Medicago truncatula Nod factor hydrolase
      1), a legume enzyme structurally related to defense-related class V chitinases
      (glycoside hydrolase family 18). MtNFH1 lacks chitinase activity but efficiently
      hydrolyzes all tested NFs of S. meliloti. The enzyme shows a high cleavage
      preference, releasing exclusively lipodisaccharides from NFs. Substrate
      specificity and kinetic properties of MtNFH1 were compared with those of class V
      chitinases from Arabidopsis (Arabidopsis thaliana) and tobacco (Nicotiana
      tabacum), which cannot hydrolyze tetrameric NFs of S. meliloti. The Michaelis
      Menten constants of MtNFH1 for NFs are in the micromolar concentration range,
      whereas nonmodified chitin oligosaccharides represent neither substrates nor
      inhibitors for MtNFH1. The three-dimensional structure of MtNFH1 was modeled on
      the basis of the known structure of class V chitinases. Docking simulation of NFs
      to MtNFH1 predicted a distinct binding cleft for the fatty acid moiety, which is
      absent in the class V chitinases. Point mutation analysis confirmed the modeled
      NF-MtNFH1 interaction. Silencing of MtNFH1 by RNA interference resulted in
      reduced NF degradation in the rhizosphere of M. truncatula. In conclusion, we
      have found a novel legume hydrolase that specifically inactivates NFs.

PMID- 24082031
TI  - Zederone, a sesquiterpene from Curcuma elata Roxb, is hepatotoxic in mice.
AB  - The present study aimed to investigate the hepatotoxicity of zederone isolated
      from Curcuma elata in mice. Adult male mice were intraperitoneally injected with
      a single dose of zederone (50-300 mg/kg body weight [BW]). Twenty-four hours
      after the injection, zederone induced liver enlargement with scattered white foci
      over the organ. The medium lethal dose (LD50) value at 24 hours of zederone was
      approximately 223 mg/kg BW. Hepatic centrilobular necrosis with marked increases
      in plasma alanine transaminase activity and total bilirubin levels was observed.
      Zederone at a dose of 200 mg/kg BW markedly decreased the activity of superoxide
      dismutase and the hepatic glutathione content, whereas the activity of catalase
      was not altered. The compound at this dose also increased the messenger RNA
      (mRNA) expression of Cyp2b10 and Cyp3a11, which are the main drug-metabolizing
      enzymes in the liver. The mRNA expression of proinflammatory cytokine tumor
      necrosis factor alpha was increased. The nuclear factor-E2-related factor 2
      protein, which is the transcription factor regulating the antioxidant gene
      expression, was decreased. The histopathology of massive hepatic centrilobular
      necrosis with an increase in the expression of cytochrome P450 (Cyp) suggests
      that the possible potentiation of zederone-induced hepatotoxicity implicated the
      induction of Cyps, which leads to the formation of biological reactive
      metabolites and that cause the oxidative stress and liver cell injuries.

PMID- 24082032
TI  - Detecting selection using time-series data of allele frequencies with multiple
      independent reference Loci.
AB  - Recently, in 2013 Feder et al. proposed the frequency increment test (FIT), which
      evaluates natural selection at a single diallelic locus by the use of time-series
      data of allele frequencies. This test is unbiased under conditions of constant
      population size and no sampling noise. Here, we expand upon the FIT by
      introducing a test that explicitly allows for changes in population size by using
      information from independent reference loci. Various demographic models suggest
      that our proposed test is unbiased irrespective of fluctuations in population
      size when sampling noise can be ignored and that it has greater power to detect
      selection than the FIT if sufficient reference loci are used. 

PMID- 24082033
TI  - Increased genomic prediction accuracy in wheat breeding through spatial
      adjustment of field trial data.
AB  - In crop breeding, the interest of predicting the performance of candidate
      cultivars in the field has increased due to recent advances in molecular breeding
      technologies. However, the complexity of the wheat genome presents some
      challenges for applying new technologies in molecular marker identification with
      next-generation sequencing. We applied genotyping-by-sequencing, a recently
      developed method to identify single-nucleotide polymorphisms, in the genomes of
      384 wheat (Triticum aestivum) genotypes that were field tested under three
      different water regimes in Mediterranean climatic conditions: rain-fed only, mild
      water stress, and fully irrigated. We identified 102,324 single-nucleotide
      polymorphisms in these genotypes, and the phenotypic data were used to train and
      test genomic selection models intended to predict yield, thousand-kernel weight,
      number of kernels per spike, and heading date. Phenotypic data showed marked
      spatial variation. Therefore, different models were tested to correct the trends
      observed in the field. A mixed-model using moving-means as a covariate was found
      to best fit the data. When we applied the genomic selection models, the accuracy
      of predicted traits increased with spatial adjustment. Multiple genomic selection
      models were tested, and a Gaussian kernel model was determined to give the
      highest accuracy. The best predictions between environments were obtained when
      data from different years were used to train the model. Our results confirm that
      genotyping-by-sequencing is an effective tool to obtain genome-wide information
      for crops with complex genomes, that these data are efficient for predicting
      traits, and that correction of spatial variation is a crucial ingredient to
      increase prediction accuracy in genomic selection models. 

PMID- 24082034
TI  - Shiga-like toxin binds with high avidity to multivalent O-linked blood group P1
      determinants on mucin-type fusion proteins.
AB  - The binding of Shiga-like toxin 1 (Stx1) and Shiga-like toxin 2 (Stx2) to a mucin
      like fusion protein, P-selectin glycoprotein ligand-1/mouse IgG2b (PSGL
      1/mIgG2b), carrying multiple copies of the blood group P1 determinant on O
      glycans was investigated with western blot and the biosensor Biacore. Chinese
      hamster ovary K-1 (CHO-K1) cells were stably transfected with linearized plasmids
      encoding the PSGL-1/mIgG2b fusion protein, the pigeon alpha1,4
      galactosyltransferase (alpha4Gal-T) and the core 2 beta1,6-N
      acetylglucosaminyltransferase (C2GnT-I). Western blot analyses of purified PSGL
      1/mIgG2b and liquid chromatography-mass spectrometry (LC-MS) of released O
      glycans confirmed the presence of the P1 determinant. Western blot analysis
      indicated strong binding of Stx1, but not Stx2, to PSGL-1/mIgG2b. In a Biacore
      assay, Stx1 and Stx2 were immobilized on a dextran chip and the binding of
      purified PSGL-1/mIgG2b and a P(k)-albumin neoglycoprotein was analyzed. Stx1 and
      Stx2 bound with high avidity to both PSGL-1/mIgG2b and P(k)-albumin, while the
      Stx1 binding was the strongest. In summary, we have shown that the pigeon
      alpha4Gal-T can be aberrantly expressed in CHO cells together with the core 2
      enzyme to generate multiple, O-linked P1 determinants on a simultaneously
      expressed mucin-type fusion protein. P1-decorated PSGL-1/mIgG2b bound with high
      avidity to both Stx1 and Stx2, and as such constitutes a potential therapeutic
      inhibitor of these toxins.

PMID- 24082035
TI  - 'High definition': not all it appears.

PMID- 24082036
TI  - Palmitoylethanolamide improves colon inflammation through an enteric glia/toll
      like receptor 4-dependent PPAR-alpha activation.
AB  - OBJECTIVE: Enteric glia activation has been reported to amplify intestinal
      inflammation via the enteroglial-specific S100B protein. This neurotrophin
      promotes macrophage recruitment in the mucosa, amplify colonic inflammation and
      interacts with toll-like receptors (TLR). Molecules inhibiting S100B-driven
      enteric activation might mitigate the course of ulcerative colitis (UC). This
      study aims to investigate the effects of palmitoylethanolammide (PEA), a drug
      able to counteract astroglial activation in the central nervous system, on
      intestinal inflammation, in humans and mice. DESIGN: Mouse models of dextran
      sodium sulphate (DSS)-induced colitis, colonic biopsies deriving from UC patients
      and primary cultures of mouse and human enteric glial cells (EGC), have been used
      to assess the effects of PEA, alone or in the presence of specific PPARalpha or
      PPARgamma antagonists, on: macroscopic signs of UC (DAI score, colon length,
      spleen weight, macrophages/neutrophils infiltration); the expression and release
      of proinflammatory markers typical of UC; TLR pathway in EGCs. RESULTS: PEA
      treatment improves all macroscopic signs of UC and decreases the expression and
      release of all the proinflammatory markers tested. PEA anti-inflammatory effects
      are mediated by the selective targeting of the S100B/TLR4 axis on ECG, causing a
      downstream inhibition of nuclear factor kappa B (NF-kB)-dependent inflammation.
      Antagonists at PPARalpha, but not PPARgamma, abolished PEA effects, in mice and
      in humans. CONCLUSIONS: Because of its lack of toxicity, its ability in reducing
      inflammation and its selective PPARalpha action, PEA might be an innovative
      molecule to broaden pharmacological strategies against UC.

PMID- 24082037
TI  - Transgenerational developmental programming.
AB  - BACKGROUND: The concept of developmental programming suggests that the early life
      environment influences offspring characteristics in later life, including the
      propensity to develop diseases such as the metabolic syndrome. There is now
      growing evidence that the effects of developmental programming may also manifest
      in further generations without further suboptimal exposure. This review considers
      the evidence, primarily from rodent models, for effects persisting to subsequent
      generations, and evaluates the mechanisms by which developmental programming may
      be transmitted to further generations. In particular, we focus on the potential
      role of the intrauterine environment in contributing to a developmentally
      programmed phenotype in subsequent generations. METHODS: The literature was
      systematically searched at http://pubmed.org and http://scholar.google.com to
      identify published findings regarding transgenerational (F2 and beyond)
      developmental programming effects in human populations and animal models.
      RESULTS: Transmission of programming effects is often viewed as a form of
      epigenetic inheritance, either via the maternal or paternal line. Evidence exists
      for both germline and somatic inheritance of epigenetic modifications which may
      be responsible for phenotypic changes in further generations. However, there is
      increasing evidence for the role of both extra-genomic components of the zygote
      and the interaction of the developing conceptus with the intrauterine environment
      in propagating programming effects. CONCLUSIONS: The contribution of a suboptimal
      reproductive tract environment or maternal adaptations to pregnancy may be
      critical to inheritance of programming effects via the maternal line. As the
      effects of age exacerbate the programmed metabolic phenotype, advancing maternal
      age may increase the likelihood of developmental programming effects being
      transmitted to further generations. We suggest that developmental programming
      effects could be propagated through the maternal line de novo in generations
      beyond F2 as a consequence of development in a suboptimally developed
      intrauterine tract and not necessarily though directly transmitted epigenetic
      mechanisms.

PMID- 24082039
TI  - The combined human sperm proteome: cellular pathways and implications for basic
      and clinical science.
AB  - BACKGROUND: The human sperm cell is very well suited for proteomic studies, as it
      is accessible, can be easily purified and is believed to be transcriptionally and
      translationally silent. The recent use of advanced proteomic approaches is
      clearly challenging the understanding of sperm biology. The aims of this review
      are to discuss the various human sperm proteomic studies, to create a compiled
      list of all the sperm proteins described to date and to re-assess the potential
      functional implications. METHODS: A search of the scientific literature available
      in the PubMed/Medline database at 31 December 2012 was conducted for studies on
      human sperm proteomics. The complete list of proteins obtained was carefully
      analysed using different bioinformatics tools, including Reactome, a
      knowledgebase of biological pathways. RESULTS: A total of 30 studies were
      identified. The proteomics studies have resulted in the identification of 6198
      different proteins, an important proportion of which (around 30%) are known to be
      expressed in the testis. The proteins were assigned to various functional
      pathways, including metabolism, apoptosis, cell cycle, meiosis and membrane
      trafficking, among others. Unexpectedly, the sperm cell also contains a range of
      proteins involved in RNA metabolism and translational regulation, as well as
      proteins usually located in organelles believed to be absent in sperm, such as
      cytoplasmatic ribosomes and peroxisomes. Additionally, some proteins whose levels
      seem to be altered in low-quality sperm might have clinical relevance.
      CONCLUSIONS: The analysis of the most complete sperm proteome available to date
      indicates the presence of several cellular protein pathways previously ignored in
      the male gamete. Confirming the activity of each of these pathways and
      understanding their biological significance will certainly boost the knowledge of
      human sperm and male fertility and infertility in the next years.

PMID- 24082038
TI  - Guidelines for the design, analysis and interpretation of 'omics' data: focus on
      human endometrium.
AB  - BACKGROUND: 'Omics' high-throughput analyses, including genomics, epigenomics,
      transcriptomics, proteomics and metabolomics, are widely applied in human
      endometrial studies. Analysis of endometrial transcriptome patterns in
      physiological and pathophysiological conditions has been to date the most
      commonly applied 'omics' technique in human endometrium. As the technologies
      improve, proteomics holds the next big promise for this field. The 'omics'
      technologies have undoubtedly advanced our knowledge of human endometrium in
      relation to fertility and different diseases. Nevertheless, the challenges
      arising from the vast amount of data generated and the broad variation of 'omics'
      profiling according to different environments and stimuli make it difficult to
      assess the validity, reproducibility and interpretation of such 'omics' data.
      With the expansion of 'omics' analyses in the study of the endometrium, there is
      a growing need to develop guidelines for the design of studies, and the analysis
      and interpretation of 'omics' data. METHODS: Systematic review of the literature
      in PubMed, and references from relevant articles were investigated up to March
      2013. RESULTS: The current review aims to provide guidelines for future 'omics'
      studies on human endometrium, together with a summary of the status and trends,
      promise and shortcomings in the high-throughput technologies. In addition, the
      approaches presented here can be adapted to other areas of high-throughput
      'omics' studies. CONCLUSION: A highly rigorous approach to future studies, based
      on the guidelines provided here, is a prerequisite for obtaining data on
      biological systems which can be shared among researchers worldwide and will
      ultimately be of clinical benefit.

PMID- 24082041
TI  - The transcriptome of follicular cells: biological insights and clinical
      implications for the treatment of infertility.
AB  - BACKGROUND: Oocyte maturation is under strict regulatory control, not only from
      intrinsic cellular processes, but also extrinsic influences. While the oocyte is
      directly connected to the surrounding cumulus cells (CCs) via a network of gap
      junctions facilitating communication and exchange of molecules, it is also
      influenced by the greater follicular environment. In order to produce an oocyte
      capable of successfully transmitting the female genetic material and able to
      support the earliest stages of preimplantation development, cytoplasmic and
      nuclear maturation must be achieved. Granulosa and CCs play an essential role in
      the maturation and competence acquisition of the developing oocyte. The fact that
      these cells are closely associated with the oocyte, share the same
      microenvironment and can be easily collected during IVF procedures makes them
      attractive targets for basic research and the development of clinically relevant
      assays. Analysis of follicular cells is likely to reveal important information
      concerning the viability and genetic constitution of their associated oocyte, as
      well as increase our understanding of normal follicular processes and the impact
      of disorders or of medical interventions such as controlled ovarian stimulation
      (COS). This review summarizes results obtained during the investigation of
      granulosa and CCs, and considers the possibilities of using follicular cells as
      surrogate markers of stimulation response during IVF, oocyte/embryo competence
      and clinical outcome. METHODS: In order to summarize the current knowledge
      obtained from the analysis of follicular cells, a thorough literature search was
      carried out. Relevant research articles published in English up to March 2013
      were reviewed. RESULTS: Multiple groups of genes expressed in follicular cells
      have been identified as possible indicators of ovulation, oocyte maturity,
      fertilization, chromosome status, ability to generate embryos capable of reaching
      the blastocyst stage of development, embryo morphology and the establishment of a
      pregnancy. However, there is a general lack of uniformity concerning groups of
      gene biomarkers among different studies. CONCLUSIONS: Extensive investigation of
      genes and proteins of granulosa and CCs has provided a detailed insight into the
      follicular microenvironment surrounding oocytes. It was evident from the data
      reviewed that the gene expression of follicular cells influences and is
      influenced by the oocyte, affecting factors such as maturity, chromosomal
      constitution, viability and competence. However, a general lack of overlap among
      genes identified as potentially useful biomarkers suggests that the transcriptome
      of follicular cells could be affected by multiple intrinsic factors, having to do
      with the patient and possibly the aetiology of infertility, as well as extrinsic
      factors, such as hormonal stimulation. Further work is required in order to
      establish a universally applicable, non-invasive test for the determination of
      oocyte competence based upon follicular cell assessment.

PMID- 24082040
TI  - The effect of combined oral contraception on testosterone levels in healthy
      women: a systematic review and meta-analysis.
AB  - BACKGROUND; Combined oral contraceptives (COCs) reduce levels of androgen,
      especially testosterone (T), by inhibiting ovarian and adrenal androgen synthesis
      and by increasing levels of sex hormone-binding globulin (SHBG). Although this
      suppressive effect has been investigated by numerous studies over many years, to
      our knowledge no systematic review concerning this issue had been performed. This
      systematic review and meta-analysis was performed to evaluate the effect of COCs
      on concentrations of total T, free T and SHBG in healthy women and to evaluate
      differences between the various types of COCs (e.g. estrogen dose, type of
      progestin) and the assays used to assess total T and free T. METHODS: A review of
      the literature was performed using database searches (MEDLINE, EMBASE and the
      Cochrane Central Register of Clinical Trials) and all publications (from
      inception date until July 2012) investigating the effect of COCs on androgen
      levels in healthy women were considered eligible for selection. Three reviewers
      were involved in study selection, data extraction and critical appraisal. For the
      meta-analysis, data on total T, free T and SHBG were extracted and combined using
      random effects analysis. Additional subgroup analyses were performed to evaluate
      differences between the various types of COCs (e.g. estrogen dose, type of
      progestin) and the assays used to assess total T or free T. RESULTS: A total of
      151 records were identified by systematic review and 42 studies with a total of
      1495 healthy young women (age range: 18-40 years) were included in the meta
      analysis. All included studies were experimental studies and 21 were non
      comparative. Pooling of the results derived from all the included papers showed
      that total T levels significantly decreased during COC use [mean difference (MD)
      (95% confidence interval, CI) -0.49 nmol/l (-0.55, -0.42); P < 0.001].
      Significantly lower levels of free T were also found [relative change (95% CI)
      0.39 (0.35, 0.43); P < 0.001], with a mean decrease of 61%. On the contrary, SHBG
      concentrations significantly increased during all types of COC use [MD (95% CI)
      99.08 nmol/l (86.43, 111.73); P < 0.001]. Subgroup analyses revealed that COCs
      containing 20-25 ug EE had similar effects on total and free T compared with COCs
      with 30-35 ug EE. In addition, suppressive effects on T levels were not different
      when comparing different types of progestins. However, subgroup analyses for the
      estrogen dose and the progestin type in relation to changes in SHBG levels did
      show significant differences: COCs containing second generation progestins and/or
      the lower estrogen doses (20-25 ug EE) were found to have less impact on SHBG
      concentrations. CONCLUSIONS: The current literature review and meta-analysis
      demonstrates that COCs decrease circulating levels of total T and free T and
      increase SBHG concentrations. Due to the SHBG increase, free T levels decrease
      twice as much as total T. The estrogen dose and progestin type of the COC do not
      influence the decline of total and free T, but both affect SHBG. The clinical
      implications of suppressed androgen levels during COC use remain to be
      elucidated.

PMID- 24082042
TI  - Systematic review and meta-analysis of intrauterine adhesions after miscarriage:
      prevalence, risk factors and long-term reproductive outcome.
AB  - BACKGROUND: Approximately 15-20% of all clinically confirmed pregnancies end in a
      miscarriage. Intrauterine adhesions (IUAs) are a possible complication after
      miscarriage, but their prevalence and the contribution of possible risk factors
      have not been elucidated yet. In addition, the long-term reproductive outcome in
      relation to IUAs has to be elucidated. METHODS: We systematically searched the
      literature for studies that prospectively assessed the prevalence and extent of
      IUAs in women who suffered a miscarriage. To be included, women diagnosed with a
      current miscarriage had to be systematically evaluated within 12 months by
      hysteroscopy after either spontaneous expulsion or medical or surgical treatment.
      Studies that included women with a history of recurrent miscarriage only or that
      evaluated the IUAs after elective abortion or beyond 12 months after the last
      miscarriage were not included. Subsequently, long-term reproductive outcomes
      after expectant (conservative), medical or surgical management were assessed in
      women with and without post-miscarriage IUAs. RESULTS: We included 10 prospective
      studies reporting on 912 women with hysteroscopic evaluation within 12 months of
      miscarriage and 8 prospective studies, including 1770 women, reporting long-term
      reproductive outcome. IUAs were detected in 183 women, resulting in a pooled
      prevalence of 19.1% [95% confidence interval (CI): 12.8-27.5%]. The extent of
      IUAs was reported in 124 women (67.8%) and was mild, moderate and severe
      respectively in 58.1, 28.2 and 13.7% of cases. Relative to women with one
      miscarriage, women with two or three or more miscarriages showed an increased
      risk of IUAs by a pooled OR of 1.41 and 2.1, respectively. The number of
      dilatation and curettage (D&C) procedures seemed to be the main driver behind
      these associations. A total of 150 congenital and acquired intrauterine
      abnormalities were encountered in 675 women, resulting in a pooled prevalence of
      22.4% (95% CI: 16.3-29.9%). Similar reproductive outcomes were reported
      subsequent to conservative, medical or surgical management for miscarriage,
      although the numbers of studies and of included women were limited. No studies
      reported long-term reproductive outcomes following post-miscarriage IUAs.
      CONCLUSIONS: IUAs are frequently encountered, in one in five women after
      miscarriage. In more than half of these, the severity and extent of the adhesions
      was mild, with unknown clinical relevance. Recurrent miscarriages and D&C
      procedures were identified as risk factors for adhesion formation. Congenital and
      acquired intrauterine abnormalities such as polyps or fibroids were frequently
      identified. There were no studies reporting on the link between IUAs and long
      term reproductive outcome after miscarriage, while similar pregnancy outcomes
      were reported subsequent to conservative, medical or surgical management.
      Although this review does not allow strong clinical conclusions on treatment
      management, it signals an important clinical problem. Treatment strategies are
      proposed to minimize the number of D&C in an attempt to reduce IUAs.

PMID- 24082043
TI  - Job strain, health behaviours and heart disease.

PMID- 24082044
TI  - Generic controlled-release oxycodone.

PMID- 24082045
TI  - Cervical screening.

PMID- 24082046
TI  - Organ donation programs needed in rural areas.

PMID- 24082047
TI  - Letter to the editor for the special issue on "The Neutrophil in Immunity".

PMID- 24082048
TI  - Editorial: CD73 deficiency and immune dysregulation in HIV infection: cause or
      effect?

PMID- 24082049
TI  - Editorial: are regulatory B10 cells a viable target for autoimmune diseases?

PMID- 24082050
TI  - yApoptosis: yeast apoptosis database.
AB  - In the past few years, programmed cell death (PCD) has become a popular research
      area due to its fundamental aspects and its links to human diseases. Yeast has
      been used as a model for studying PCD, since the discovery of morphological
      markers of apoptotic cell death in yeast in 1997. Increasing knowledge in
      identification of components and molecular pathways created a need for
      organization of information. To meet the demands from the research community, we
      have developed a curated yeast apoptosis database, yApoptosis. The database
      structurally collects an extensively curated set of apoptosis, PCD and related
      genes, their genomic information, supporting literature and relevant external
      links. A web interface including necessary functions is provided to access and
      download the data. In addition, we included several networks where the apoptosis
      genes or proteins are involved, and present them graphically and interactively to
      facilitate rapid visualization. We also promote continuous inputs and curation by
      experts. yApoptosis is a highly specific resource for sharing information online,
      which supports researches and studies in the field of yeast apoptosis and cell
      death. DATABASE URL: http://www.ycelldeath.com/yapoptosis/.

PMID- 24082051
TI  - Plasma metanephrine for assessing the selectivity of adrenal venous sampling.
AB  - Adrenal vein sampling is used to establish the origins of excess production of
      adrenal hormones in primary aldosteronism. Correct catheter positioning is
      confirmed using adrenal vein measurements of cortisol, but this parameter is not
      always reliable. Plasma metanephrine represents an alternative parameter. The
      objective of our study was to determine the use of plasma metanephrine
      concentrations to establish correct catheter positioning during adrenal vein
      sampling with and without cosyntropin stimulation. We included 52 cosyntropin
      stimulated and 34 nonstimulated sequential procedures. Plasma cortisol and
      metanephrine concentrations were measured in adrenal and peripheral venous
      samples. Success rates of sampling, using an adrenal to peripheral cortisol
      selectivity index of 3.0, were compared with success rates of metanephrine using
      a selectivity index determined by receiver operating characteristic curve
      analysis. Among procedures assessed as selective using cortisol, the adrenal to
      peripheral vein ratio of metanephrine was 6-fold higher than that of cortisol
      (94.0 versus 15.5; P<0.0001). There were significant positive relationships
      between adrenal to peripheral vein ratios of cortisol and metanephrine for
      cosyntropin-stimulated samplings but not for nonstimulated samplings. Receiver
      operating characteristic curve analysis indicated a plasma metanephrine
      selectivity index cutoff of 12. Using this cutoff, concordance in sampling
      success rates determined by cortisol and metanephrine was substantially higher in
      cosyntropin-stimulated than in nonstimulated samplings (98% versus 59%). For the
      latter procedures, sampling success rates determined by metanephrine were higher
      (P<0.01) than those determined by cortisol (91% versus 56%). In conclusion,
      metanephrine provides a superior analyte compared with cortisol in assessing the
      selectivity of adrenal vein sampling during procedures without cosyntropin
      stimulation. 

PMID- 24082053
TI  - KCNQ channels and novel insights into coronary perfusion.

PMID- 24082052
TI  - Somatic ATP1A1, ATP2B3, and KCNJ5 mutations in aldosterone-producing adenomas.
AB  - Aldosterone-producing adenomas (APAs) cause a sporadic form of primary
      aldosteronism and somatic mutations in the KCNJ5 gene, which encodes the G
      protein-activated inward rectifier K(+) channel 4, GIRK4, account for ~40% of
      APAs. Additional somatic APA mutations were identified recently in 2 other genes,
      ATP1A1 and ATP2B3, encoding Na(+)/K(+)-ATPase 1 and Ca(2+)-ATPase 3,
      respectively, at a combined prevalence of 6.8%. We have screened 112 APAs for
      mutations in known hotspots for genetic alterations associated with primary
      aldosteronism. Somatic mutations in ATP1A1, ATP2B3, and KCNJ5 were present in
      6.3%, 0.9%, and 39.3% of APAs, respectively, and included 2 novel mutations
      (Na(+)/K(+)-ATPase p.Gly99Arg and GIRK4 p.Trp126Arg). CYP11B2 gene expression was
      higher in APAs harboring ATP1A1 and ATP2B3 mutations compared with those without
      these or KCNJ5 mutations. Overexpression of Na(+)/K(+)-ATPase p.Gly99Arg and
      GIRK4 p.Trp126Arg in HAC15 adrenal cells resulted in upregulation of CYP11B2 gene
      expression and its transcriptional regulator NR4A2. Structural modeling of the
      Na(+)/K(+)-ATPase showed that the Gly99Arg substitution most likely interferes
      with the gateway to the ion binding pocket. In vitro functional assays
      demonstrated that Gly99Arg displays severely impaired ATPase activity, a reduced
      apparent affinity for Na(+) activation of phosphorylation and K(+) inhibition of
      phosphorylation that indicate decreased Na(+) and K(+) binding, respectively.
      Moreover, whole cell patch-clamp studies established that overexpression of
      Na(+)/K(+)-ATPase Gly99Arg causes membrane voltage depolarization. In conclusion,
      somatic mutations are common in APAs that result in an increase in CYP11B2 gene
      expression and may account for the dysregulated aldosterone production in a
      subset of patients with sporadic primary aldosteronism. 

PMID- 24082054
TI  - Physical activity and risk of hypertension: a meta-analysis of prospective cohort
      studies.
AB  - Published literature reports controversial results about the association of
      physical activity (PA) with risk of hypertension. A meta-analysis of prospective
      cohort studies was performed to investigate the effect of PA on hypertension
      risk. PubMed and Embase databases were searched to identify all related
      prospective cohort studies. The Q test and I(2) statistic were used to examine
      between-study heterogeneity. Fixed or random effects models were selected based
      on study heterogeneity. A funnel plot and modified Egger linear regression test
      were used to estimate publication bias. Thirteen prospective cohort studies were
      identified, including 136,846 persons who were initially free of hypertension,
      and 15,607 persons developed hypertension during follow-up. The pooled relative
      risk (RR) of main results from these studies suggests that both high and moderate
      levels of recreational PA were associated with decreased risk of hypertension
      (high versus low: RR, 0.81; 95% confidence interval, 0.76-0.85 and moderate
      versus low: RR, 0.89; 95% confidence interval, 0.85-0.94). The association of
      high or moderate occupational PA with decreased hypertension risk was not
      significant (high versus low: RR, 0.93; 95% confidence interval, 0.81-1.08 and
      moderate versus low: RR, 0.96; 95% confidence interval, 0.87-1.06). No
      publication bias was observed. The results of this meta-analysis suggested that
      there was an inverse dose-response association between levels of recreational PA
      and risk of hypertension, whereas there was no significant association between
      occupational PA and hypertension.

PMID- 24082055
TI  - Association between circulating endostatin, hypertension duration, and
      hypertensive target-organ damage.
AB  - Our aim is to study associations between circulating endostatin, hypertension
      duration, and hypertensive target-organ damage. Long-term hypertension induces
      cardiovascular and renal remodeling. Circulating endostatin, a biologically
      active derivate of collagen XVIII, has been suggested to be a relevant marker for
      extracellular matrix turnover and remodeling in various diseases. However, the
      role of endostatin in hypertension and hypertensive target-organ damage is
      unclear. Serum endostatin was measured in 2 independent community-based cohorts:
      the Prospective Investigation of the Vasculature in Uppsala Seniors (PIVUS; women
      51%; n = 812; mean age, 75 years) and the Uppsala Longitudinal Study of Adult Men
      (ULSAM; n=785; mean age, 77.6 years). Retrospective data on blood pressure
      measurements and antihypertensive medication (PIVUS >5 years, ULSAM >27 years),
      and cross-sectional data on echocardiographic left ventricular mass, endothelial
      function (endothelium-dependent vasodilation assessed by the invasive forearm
      model), and urinary albumin/creatinine ratio were available. In PIVUS,
      participants with >= 5 years of history of hypertension portrayed 0.42 SD (95%
      confidence interval, 0.23-0.61; P<0.001) higher serum endostatin, compared with
      that of normotensives. This association was replicated in ULSAM, in which
      participants with 27 years hypertension duration had the highest endostatin (0.57
      SD higher; 95% confidence interval, 0.35-0.80; P<0.001). In addition, higher
      endostatin was associated with higher left ventricular mass, worsened endothelial
      function, and higher urinary albumin/creatinine ratio (P<0.03 for all) in
      participants with prevalent hypertension. Circulating endostatin is associated
      with the duration of hypertension, and vascular, myocardial, and renal indices of
      hypertensive target-organ damage. Further studies are warranted to assess the
      prognostic role of endostatin in individuals with hypertension.

PMID- 24082056
TI  - Blood dust as active circulating cellular representatives during gestational
      vascular complications.

PMID- 24082057
TI  - Microvesicles of women with gestational hypertension and preeclampsia affect
      human trophoblast fate and endothelial function.
AB  - Microvesicles shedding from cell membrane affect inflammation, apoptosis, and
      angiogenesis. We hypothesize that microvesicles of women with gestational
      vascular complications reflect pathophysiological state of the patients and
      affect their endothelial and trophoblast cell function. Microvesicles of healthy
      pregnant women, women with gestational hypertension, mild, or severe
      preeclampsia/toxemia, were characterized, and their effects on early-stage or
      term trophoblasts and endothelial cells were evaluated using apoptosis,
      migration, and tube formation assays. Patient subgroups differed significantly
      only in proteinuria levels, therefore their microvesicles were assessed as 1
      group, demonstrating higher levels of inflammatory and angiogenic proteins
      compared with those of healthy pregnant women. In endothelial cells,
      microvesicles of healthy pregnant women reduced caspase 3/7 activity, increased
      migration, and induced tube formation. These processes were suppressed by
      microvesicles of women with gestational vascular complications. In early-stage
      trophoblasts, microvesicles of healthy pregnant women decreased apoptosis
      compared with untreated cells (6+/-5% versus 13.8+/-5.8%; P<0.001) and caspase
      3/7 activity and induced higher migration (39.7+/-10.1 versus 20.3+/-8.3 mm2;
      P<0.001). This effect was mediated through extracellular signal-regulated kinase
      pathway. Conversely, microvesicles of women with gestational vascular
      complications increased term trophoblast apoptosis compared with cells exposed to
      microvesicles of healthy pregnant women (15.1+/-3.3% versus 6.5+/-2.1%; P<0.001)
      and inhibited early-stage trophoblasts migration (21.4+/-18.5 versus 39.7+/-10.1
      mm2; P<0.001). In conclusion, microvesicle content and effects on endothelial and
      trophoblast cells vary according to the physiological/pathological state of a
      pregnant woman. Microvesicles seem to play a pivotal role in the course of
      pregnancy, which could potentially result in gestational vascular complications.

PMID- 24082058
TI  - Newly discovered components and actions of the renin-angiotensin system.

PMID- 24082059
TI  - Contribution of Kv7 channels to basal coronary flow and active response to
      ischemia.
AB  - The goal of the present study was to determine the role of KCNQ-encoded Kv
      channels (Kv7 channels) in the passive and active regulation of coronary flow in
      normotensive and hypertensive rats. In left anterior descending coronary arteries
      from normotensive rats, structurally different Kv7.2 to 7.5 activators produced
      relaxations, which were considerably less in arteries from hypertensive rats and
      were not mimicked by the Kv7.1-specific activator R-L3. In isolated, perfused
      heart preparations, coronary flow rate increased in response to the Kv7.2 to 7.5
      activator (S)-1 and was diminished in the presence of a Kv7 inhibitor. The
      expression levels of KCNQ1-5 and their known accessory KCNE1-5 subunits in
      coronary arteries were similar in normotensive and hypertensive rats as measured
      by quantitative polymerase chain reaction. However, Kv7.4 protein expression was
      reduced in hypertensive rats. Application of adenosine or A2A receptor agonist
      CGS-21680 produced concentration-dependent relaxations of coronary arteries from
      normotensive rats, which were attenuated by application of Kv7 inhibitors. Kv7
      blockers also attenuated the ischemia-induced increase in coronary perfusion in
      Langendorff studies. Overall, these data establish Kv7 channels as crucial
      regulators of coronary flow at resting and after hypoxic insult. 

PMID- 24082060
TI  - Ins and outs of aldosterone-producing adenomas of the adrenal: from channelopathy
      to common curable cause of hypertension.

PMID- 24082061
TI  - L-type calcium channel inhibitor diltiazem prevents aneurysm formation by blood
      pressure-independent anti-inflammatory effects.
AB  - Formation of abdominal aortic aneurysms is a progressive inflammatory process
      that involves infiltration and differentiation of monocytes in the vessel wall,
      proliferation and migration of smooth muscle cells, and eventually the
      degradation of the internal elastic lamina, which leads to outward vascular
      remodeling and distension of the vessel. Because calcium channel blockers exert
      multiple beneficial effects on the vascular system, we investigated the effect of
      the benzothiazepine-type calcium channel blocker diltiazem on aneurysm formation
      in a mouse model. Angiotensin II infusion induced massive suprarenal aortic
      aneurysm formation in male apolipoprotein E-deficient mice that was blocked by
      cotreatment with diltiazem even if the blood pressure was controlled by
      coinfusion of phenylephrine. Diltiazem prevented the angiotensin II-mediated
      induction of proinflammatory cytokines after 7 days of angiotensin II treatment
      in the aortic arch attributable to a reduction in the amount of locally
      infiltrating macrophages. To identify the underlying mechanism, vascular segments
      and cultured vascular cells as well as monocytes were studied. Diltiazem failed
      to reduce the angiotensin II-induced expression of proinflammatory chemokines and
      cytokines in isolated mouse thoracic aortic segments in organ culture.
      Furthermore, diltiazem did not affect the recruitment of proinflammatory Ly6C(+)
      monocytes in vivo pointing toward an effect of the compound on gene expression in
      monocytes/macrophages. Indeed, diltiazem prevented the interleukin-6-induced mRNA
      expression of interleukin-1beta and the monocyte chemoattractant protein CCL12 in
      peritoneal macrophages and RAW264.7 cells independent of the intracellular
      calcium concentration. Thus, diltiazem limits aortic aneurysm formation in mice
      by a blood pressure-independent anti-inflammatory effect on monocytic cells. 

PMID- 24082062
TI  - Social epidemiology of hypertension stages.

PMID- 24082063
TI  - Are aldosterone levels inappropriately low in preeclampsia?

PMID- 24082064
TI  - Discovery of a linoleate 9S-dioxygenase and an allene oxide synthase in a fusion
      protein of Fusarium oxysporum.
AB  - Fusarium oxysporum is a devastating plant pathogen that oxidizes C18 fatty acids
      sequentially to jasmonates. The genome codes for putative dioxygenase (DOX)
      cytochrome P450 (CYP) fusion proteins homologous to linoleate diol synthases
      (LDSs) and the allene oxide synthase (AOS) of Aspergillus terreus, e.g.,
      FOXB_01332. Recombinant FOXB_01332 oxidized 18:2n-6 to 9S-hydroperoxy-10(E),12(Z)
      octadecadienoic acid by hydrogen abstraction and antarafacial insertion of
      molecular oxygen and sequentially to an allene oxide, 9S(10)-epoxy-10,12(Z)
      octadecadienoic acid, as judged from nonenzymatic hydrolysis products (alpha- and
      gamma-ketols). The enzyme was therefore designated 9S-DOX-AOS. The 9S-DOX
      activity oxidized C18 and C20 fatty acids of the n-6 and n-3 series to
      hydroperoxides at the n-9 and n-7 positions, and the n-9 hydroperoxides could be
      sequentially transformed to allene oxides with only a few exceptions. The AOS
      activity was stereospecific for 9- and 11-hydroperoxides with S configurations.
      FOXB_01332 has acidic and alcoholic residues, Glu946-Val-Leu-Ser949, at positions
      of crucial Asn and Gln residues (Asn-Xaa-Xaa-Gln) of the AOS and LDS. Site
      directed mutagenesis studies revealed that FOXB_01332 and AOS of A. terreus
      differ in catalytically important residues suggesting that AOS of A. terreus and
      F. oxysporum belong to different subfamilies. FOXB_01332 is the first linoleate 9
      DOX with homology to animal heme peroxidases and the first 9-DOX-AOS fusion
      protein.

PMID- 24082065
TI  - TCE, designated a known carcinogen, now the focus of ongoing research.

PMID- 24082066
TI  - Young-adult cancer survivors face unique challenges.

PMID- 24082068
TI  - Surface charge of Streptococcus pneumoniae predicts serotype distribution.
AB  - Streptococcus pneumoniae (pneumococcus) frequently colonizes the human
      nasopharynx and is an important cause of pneumonia, meningitis, sinusitis, and
      otitis media. The outer cell surface of pneumococcus may assume various degrees
      of negative charge depending on the polysaccharide capsule, of which more than 90
      serotypes have been identified. The negative charge of capsular polysaccharides
      has been proposed to electrostatically repel pneumococci from phagocytic cells,
      and avoidance of phagocytosis correlates with higher carriage prevalence. We
      hypothesized that the surface charge of pneumococcus contributes to its success
      in nasopharyngeal carriage by modulating resistance to phagocyte-mediated
      killing. Here, we measured the surface charge (zeta potential) of laboratory
      constructed strains that share a genetic background but differ in serotype and of
      clinical strains that differ in serotype and genetic background. A more negative
      surface charge correlated with higher resistance to nonopsonic killing by human
      neutrophils in vitro. In addition, a more negative zeta potential was associated
      with higher carriage prevalence in human populations before and after the
      widespread use of the pneumococcal conjugate vaccine PCV7. We also confirmed that
      capsule is the major determinant of net surface charge in clinical isolates with
      diverse backgrounds. We noted that exceptions exist to the idea that a higher
      magnitude of negative charge predicts higher prevalence. The results indicated
      that zeta potential is strongly influenced by pneumococcal capsule type but is
      unlikely to be the only important mechanism by which capsule interacts with host.

PMID- 24082069
TI  - Capsular sialic acid of Streptococcus suis serotype 2 binds to swine influenza
      virus and enhances bacterial interactions with virus-infected tracheal epithelial
      cells.
AB  - Streptococcus suis serotype 2 is an important swine bacterial pathogen, and it is
      also an emerging zoonotic agent. It is unknown how S. suis virulent strains,
      which are usually found in low quantities in pig tonsils, manage to cross the
      first host defense lines to initiate systemic disease. Influenza virus produces a
      contagious infection in pigs which is frequently complicated by bacterial
      coinfections, leading to significant economic impacts. In this study, the effect
      of a preceding swine influenza H1N1 virus (swH1N1) infection of swine tracheal
      epithelial cells (NTPr) on the ability of S. suis serotype 2 to adhere to,
      invade, and activate these cells was evaluated. Cells preinfected with swH1N1
      showed bacterial adhesion and invasion levels that were increased more than 100
      fold compared to those of normal cells. Inhibition studies confirmed that the
      capsular sialic acid moiety is responsible for the binding to virus-infected cell
      surfaces. Also, preincubation of S. suis with swH1N1 significantly increased
      bacterial adhesion to/invasion of epithelial cells, suggesting that S. suis also
      uses swH1N1 as a vehicle to invade epithelial cells when the two infections occur
      simultaneously. Influenza virus infection may facilitate the transient passage of
      S. suis at the respiratory tract to reach the bloodstream and cause bacteremia
      and septicemia. S. suis may also increase the local inflammation at the
      respiratory tract during influenza infection, as suggested by an exacerbated
      expression of proinflammatory mediators in coinfected cells. These results give
      new insight into the complex interactions between influenza virus and S. suis in
      a coinfection model. 

PMID- 24082070
TI  - B cell activating factor inhibition impairs bacterial immunity by reducing T cell
      independent IgM secretion.
AB  - B cell activating factor of the tumor necrosis factor family (BAFF) is an
      essential survival factor for B cells and has been shown to regulate T cell
      independent (TI) IgM production. During Ehrlichia muris infection, TI IgM
      secretion in the spleen was BAFF dependent, and antibody-mediated BAFF
      neutralization led to an impairment of IgM-mediated host defense. The failure of
      TI plasmablasts to secrete IgM was not a consequence of alterations in their
      generation, survival, or early differentiation, since all occurred normally in
      infected mice following BAFF neutralization. Gene expression characteristic of
      plasma cell differentiation was also unaffected by BAFF neutralization in vivo,
      and except for CD138, plasmablast cell surface marker expression was unaffected.
      IgM was produced, since it was detected intracellularly, and impaired secretion
      was not due to a failure to express the IgM secretory exon. Addition of BAFF to
      plasmablasts in vitro rescued IgM secretion, suggesting that BAFF signaling can
      directly regulate secretory processes. Our findings indicate that BAFF signaling
      can modulate TI host defense by acting at a late stage in B cell differentiation,
      via its regulation of terminal plasmablast differentiation and/or IgM secretion. 

PMID- 24082071
TI  - Significance of the D-serine-deaminase and D-serine metabolism of Staphylococcus
      saprophyticus for virulence.
AB  - Staphylococcus saprophyticus is the only species of Staphylococcus that is
      typically uropathogenic and possesses a gene coding for a D-serine-deaminase
      (DsdA). As D-serine is prevalent in urine and toxic or bacteriostatic to many
      bacteria, it is not surprising that the D-serine-deaminase gene is found in the
      genome of uropathogens. It has been suggested that D-serine-deaminase or the
      ability to respond to or to metabolize D-serine is important for virulence. For
      uropathogenic Escherichia coli (UPEC), a high intracellular D-serine
      concentration affects expression of virulence factors. S. saprophyticus is able
      to grow in the presence of high D-serine concentrations; however, its D-serine
      metabolism has not been described. The activity of the D-serine-deaminase was
      verified by analyzing the formation of pyruvate from D-serine in different
      strains with and without D-serine-deaminase. Cocultivation experiments were
      performed to show that D-serine-deaminase confers a growth advantage to S.
      saprophyticus in the presence of D-serine. Furthermore, in vivo coinfection
      experiments showed a disadvantage for the DeltadsdA mutant during urinary tract
      infection. Expression analysis of known virulence factors by reverse
      transcription-quantitative PCR (RT-qPCR) showed that the surface-associated
      lipase Ssp is upregulated in the presence of D-serine. In addition, we show that
      S. saprophyticus is able to use D-serine as the sole carbon source, but
      interestingly, D-serine had a negative effect on growth when glucose was also
      present. Taken together, D-serine metabolism is associated with virulence in S.
      saprophyticus, as at least one known virulence factor is upregulated in the
      presence of D-serine and a DeltadsdA mutant was attenuated in virulence murine
      model of urinary tract infection.

PMID- 24082072
TI  - Nlrp-3-driven interleukin 17 production by gammadeltaT cells controls infection
      outcomes during Staphylococcus aureus surgical site infection.
AB  - Recent work has identified T cells and the cytokines they produce as important
      correlates of immune protection during Staphylococcus aureus infections through
      the ability of these T cells to regulate local neutrophil responses. However, the
      specific T-cell subsets that are involved in coordinating protection at distinct
      sites of infection remains to be established. In this study, we identify for the
      first time an important role for gammadeltaT cells in controlling S. aureus
      surgical site infection (SSI). gammadeltaT cells are recruited to the wound site
      following S. aureus challenge, where they represent the primary source of
      interleukin 17 (IL-17), with a small contribution from other non-gammadeltaT
      cells. The IL-17 response is entirely dependent upon IL-1 receptor signaling.
      Using IL-17 receptor-deficient mice, we demonstrate that IL-17 is required to
      control bacterial clearance during S. aureus SSI. However, we demonstrate a
      strain-dependent requirement for gammadeltaT cells in this process due to the
      differential abilities of individual strains to activate IL-1beta production. IL
      1beta processing relies upon activation of the Nlrp3 inflammasome complex, and we
      demonstrate that Nlrp3-deficient and IL-1 receptor-deficient mice have an
      impaired ability to control S. aureus SSI due to reduced production of IL-17 by
      gammadeltaT cells at the site of infection. Given that IL-17 has been identified
      as an important correlate of immune protection during S. aureus infection, it is
      vital that the unique cellular sources of this cytokine and mechanisms inducing
      its activation are identified at distinct sites of infection. Our study
      demonstrates that while IL-17 may be critically important for mediating immune
      protection during S. aureus SSI, the relative contribution of gammadeltaT cells
      to these protective effects may be strain dependent. 

PMID- 24082073
TI  - Differential roles of ASK1 and TAK1 in Helicobacter pylori-induced cellular
      responses.
AB  - The mitogen-activated protein kinase (MAPK) signaling pathway regulates various
      cellular functions, including those induced by Helicobacter pylori. TAK1 is an
      upstream MAPK kinase kinase (MAP3K) required for H. pylori-induced MAPK and NF
      kappaB activation, but it remains unclear whether other MAP3Ks are involved in H.
      pylori-induced cellular responses. In this study, we focused on the MAP3K ASK1,
      which plays a critical role in gastric tumorigenesis. In gastric epithelial
      cells, H. pylori activates ASK1 in a reactive oxygen species (ROS)- and cag
      pathogenicity island-dependent manner, and ASK1 regulates sustained JNK
      activation and apoptosis induced by H. pylori. In contrast, TAK1 regulates H.
      pylori-mediated early JNK activation and cytokine production. We also found
      reciprocal regulation between ASK1 and TAK1 in H. pylori-related responses,
      whereby inhibition of TAK1 or downstream p38 MAPK activates ASK1 through ROS
      production, and ASK1 suppresses TAK1 and downstream NF-kappaB activation. We
      identified ROS/ASK1/JNK as a new signaling pathway induced by H. pylori, which
      regulates apoptotic cell death. The balance of ASK1-induced apoptosis and TAK1
      induced antiapoptotic or inflammatory responses may determine the fate of
      epithelial cells infected with H. pylori and thus be involved in the pathogenesis
      of gastritis and gastric cancer. 

PMID- 24082074
TI  - Within-host selection is limited by an effective population of Streptococcus
      pneumoniae during nasopharyngeal colonization.
AB  - Streptococcus pneumoniae (pneumococcus) is a significant pathogen that frequently
      colonizes the human nasopharynx. Environmental factors, including antimicrobial
      use and host immunity, exert selection on members of the nasopharyngeal
      population, and the dynamics of selection are influenced by the effective
      population size of the selected population, about which little is known. We
      measured here the variance effective population size (N(e)) of pneumococcus in a
      mouse colonization model by monitoring the frequency change of two cocolonizing,
      competitively neutral pneumococcal strains over time. The point estimate of N(e)
      during nasal carriage in 16 BALB/c mice was 133 (95% confidence interval [CI] =
      11 to 203). In contrast, the lower-bound census population exhibited a mean of
      5768 (95% CI = 2,515 to 9,021). Therefore, pneumococcal N(e) during nasal
      carriage is substantially smaller than the census population. The N(e) during day
      1 to day 4 of colonization was comparable to the Ne during day 4 to day 8.
      Similarly, a low Ne was also evident for the colonization of pneumococcus in
      BALB/c mice exposed to cholera toxin 4 weeks prior to challenge and in another
      mouse strain (DO11.10 RAG(-/-)). We developed a mathematical model of
      pneumococcal colonization composed of two subpopulations with differential
      contribution to future generations. By stochastic simulation, this model can
      reproduce the pattern of observed pneumococcal N(e) and predicts that the
      selection coefficients may be difficult to measure in vivo. We hypothesized that
      such a small N(e) may reduce the effectiveness of within host selection for
      pneumococcus.

PMID- 24082075
TI  - Impaired innate mucosal immunity in aged mice permits prolonged Streptococcus
      pneumoniae colonization.
AB  - Streptococcus pneumoniae is a frequent asymptomatic colonizer of the
      nasopharyngeal niche and only occasionally progresses toward infection. The
      burden of pneumococcal disease is particularly high in the elderly, and the
      mechanisms behind this increased susceptibility are poorly understood. Here we
      used a mouse model of pneumococcal carriage to study immunosenescence in the
      upper respiratory tract (URT). Nasal mucosa-associated lymphoid tissue (NALT)
      showed increased expression of Toll-like receptor 1, interleukin-1beta, NLRp3
      inflammasome, and CCL2 in naive elderly compared to young animals. This suggests
      an increased proinflammatory expression profile in the NALT of aged mice at
      baseline. Simultaneously, we observed a more tolerogenic profile in respiratory
      epithelia of naive elderly compared to young adult mice with upregulation of the
      NF-kappabeta pathway inhibitor peroxisome proliferator-activated receptor gamma
      (PPARgamma). After nasal instillation of pneumococci, pneumococcal colonization
      was prolonged in elderly mice compared to in young adults. The delay in clearance
      was associated with absent or delayed upregulation of a proinflammatory
      mediator(s) in the NALT, diminished influx of macrophages into the URT niche, and
      absent downregulation of PPARgamma in respiratory epithelium, accompanied by
      diminished expression of cathelicidin (CRAMP) at the site of colonization. These
      findings suggest that unresponsiveness to pneumococcal challenge due to altered
      mucosal immune regulation is the key to increased susceptibility to disease in
      the elderly. 

PMID- 24082076
TI  - Differences in purinergic amplification of osmotic cell lysis by the pore-forming
      RTX toxins Bordetella pertussis CyaA and Actinobacillus pleuropneumoniae ApxIA:
      the role of pore size.
AB  - A large subgroup of the repeat in toxin (RTX) family of leukotoxins of Gram
      negative pathogens consists of pore-forming hemolysins. These can permeabilize
      mammalian erythrocytes (RBCs) and provoke their colloid osmotic lysis (hemolytic
      activity). Recently, ATP leakage through pannexin channels and P2X receptor
      mediated opening of cellular calcium and potassium channels were implicated in
      cell permeabilization by pore-forming toxins. In the study described here, we
      examined the role played by purinergic signaling in the cytolytic action of two
      RTX toxins that form pores of different sizes. The cytolytic potency of ApxIA
      hemolysin of Actinobacillus pleuropneumoniae, which forms pores about 2.4 nm
      wide, was clearly reduced in the presence of P2X7 receptor antagonists or an ATP
      scavenger, such as pyridoxalphosphate-6-azophenyl-2',4'-disulfonic acid (PPADS),
      Brilliant Blue G, ATP oxidized sodium salt, or hexokinase. In contrast,
      antagonists of purinergic signaling had no impact on the hemolytic potency of the
      adenylate cyclase toxin-hemolysin (CyaA) of Bordetella pertussis, which forms
      pores of 0.6 to 0.8 nm in diameter. Moreover, the conductance of pores formed by
      ApxIA increased with the toxin concentration, while the conductance of the CyaA
      single pore units was constant at various toxin concentrations. However, the P2X7
      receptor antagonist PPADS inhibited in a concentration-dependent manner the
      exacerbated hemolytic activity of a CyaA-DeltaN489 construct (lacking 489 N
      terminal residues of CyaA), which exhibited a strongly enhanced pore-forming
      propensity (>20-fold) and also formed severalfold larger conductance units in
      planar lipid bilayers than intact CyaA. These results point to a pore size
      threshold of purinergic amplification involvement in cell permeabilization by
      pore-forming RTX toxins. 

PMID- 24082077
TI  - Coxiella burnetii interaction with neutrophils and macrophages in vitro and in
      SCID mice following aerosol infection.
AB  - Coxiella burnetii is an obligate intracellular bacterium that causes acute and
      chronic Q fever in humans. Human Q fever is mainly transmitted by aerosol
      infection. However, there is a fundamental gap in the knowledge regarding the
      mechanisms of pulmonary immunity against C. burnetii infection. This study
      focused on understanding the interaction between C. burnetii and innate immune
      cells in vitro and in vivo. Both virulent C. burnetii Nine Mile phase I (NMI) and
      avirulent Nine Mile phase II (NMII) were able to infect neutrophils, while the
      infection rates were lower than 29%, suggesting that C. burnetii can infect
      neutrophils, but infection is limited. Interestingly, C. burnetii inside
      neutrophils can infect and replicate within macrophages, suggesting that
      neutrophils cannot kill C. burnetii and C. burnetii may be using infection of
      neutrophils as an evasive strategy to infect macrophages. To elucidate the
      mechanisms of the innate immune response to C. burnetii natural infection, SCID
      mice were exposed to aerosolized C. burnetii. Surprisingly, neutrophil influx
      into the lungs was delayed until day 7 postinfection in both NMI- and NMII
      infected mice. This result suggests that neutrophils may play a unique role in
      the early immune response against aerosolized C. burnetii. Studying the
      interaction between C. burnetii and the innate immune system can provide a model
      system for understanding how the bacteria evade early immune responses to cause
      infection. 

PMID- 24082078
TI  - The Pseudomonas aeruginosa periplasmic protease CtpA can affect systems that
      impact its ability to mount both acute and chronic infections.
AB  - Proteases play important roles in the virulence of Pseudomonas aeruginosa. Some
      are exported to act on host targets and facilitate tissue destruction and
      bacterial dissemination. Others work within the bacterial cell to process
      virulence factors and regulate virulence gene expression. Relatively little is
      known about the role of one class of bacterial serine proteases known as the
      carboxyl-terminal processing proteases (CTPs). The P. aeruginosa genome encodes
      two CTPs annotated as PA3257/Prc and PA5134/CtpA in strain PAO1. Prc degrades
      mutant forms of the anti-sigma factor MucA to promote mucoidy in some cystic
      fibrosis lung isolates. However, nothing is known about the role or importance of
      CtpA. We have now found that endogenous CtpA is a soluble periplasmic protein and
      that a ctpA null mutant has specific phenotypes consistent with an altered cell
      envelope. Although a ctpA null mutation has no major effect on bacterial growth
      in the laboratory, CtpA is essential for the normal function of the type 3
      secretion system (T3SS), for cytotoxicity toward host cells, and for virulence in
      a mouse model of acute pneumonia. Conversely, increasing the amount of CtpA above
      its endogenous level induces an uncharacterized extracytoplasmic function sigma
      factor regulon, an event that has been reported to attenuate P. aeruginosa in a
      rat model of chronic lung infection. Therefore, a normal level of CtpA activity
      is critical for T3SS function and acute virulence, whereas too much activity can
      trigger an apparent stress response that is detrimental to chronic virulence. 

PMID- 24082079
TI  - Pseudomonas aeruginosa outer membrane vesicles modulate host immune responses by
      targeting the Toll-like receptor 4 signaling pathway.
AB  - Bacteria can naturally secrete outer membrane vesicles (OMVs) as pathogenic
      factors, while these vesicles may also serve as immunologic regulators if
      appropriately prepared. However, it is largely unknown whether Pseudomonas
      aeruginosa OMVs can activate inflammatory responses and whether immunization with
      OMVs can provide immune protection against subsequent infection. We purified and
      identified OMVs, which were then used to infect lung epithelial cells in vitro as
      well as C57BL/6J mice to investigate the immune response and the underlying
      signaling pathway. The results showed that OMVs generated from P. aeruginosa wild
      type strain PAO1 were more cytotoxic to alveolar epithelial cells than those from
      quorum-sensing (QS)-deficient strain PAO1-DeltalasR. The levels of Toll-like
      receptor 4 (TLR4) and proinflammatory cytokines, including interleukin-1beta (IL
      1beta) and IL-6, increased following OMV infection. Compared with
      lipopolysaccharide (LPS), lysed OMVs in which the membrane structures were broken
      induced a weak immune response. Furthermore, expression levels of TLR4-mediated
      responders (i.e., cytokines) were markedly downregulated by the TLR4 inhibitor
      E5564. Active immunization with OMVs or passive transfer of sera with a high
      cytokine quantity acquired from OMV-immunized mice could protect healthy mice
      against subsequent lethal PAO1 challenges (1.5 * 10(11) CFU). Collectively, these
      findings indicate that naturally secreted P. aeruginosa OMVs may trigger
      significant inflammatory responses via the TLR4 signaling pathway and protect
      mice against pseudomonal lung infection. 

PMID- 24082080
TI  - Vaginolysin drives epithelial ultrastructural responses to Gardnerella vaginalis.
AB  - Gardnerella vaginalis, the bacterial species most frequently isolated from women
      with bacterial vaginosis (BV), produces a cholesterol-dependent cytolysin (CDC),
      vaginolysin (VLY). At sublytic concentrations, CDCs may initiate complex
      signaling cascades crucial to target cell survival. Using live-cell imaging, we
      observed the rapid formation of large membrane blebs in human vaginal and
      cervical epithelial cells (VK2 and HeLa cells) exposed to recombinant VLY toxin
      and to cell-free supernatants from growing liquid cultures of G. vaginalis.
      Binding of VLY to its human-specific receptor (hCD59) is required for bleb
      formation, as antibody inhibition of either toxin or hCD59 abrogates this
      response, and transfection of nonhuman cells (CHO-K1) with hCD59 renders them
      susceptible to toxin-induced membrane blebbing. Disruption of the pore formation
      process (by exposure to pore-deficient toxoids or pretreatment of cells with
      methyl-beta-cyclodextrin) or osmotic protection of target cells inhibits VLY
      induced membrane blebbing. These results indicate that the formation of
      functional pores drives the observed ultrastructural rearrangements. Rapid bleb
      formation may represent a conserved response of epithelial cells to sublytic
      quantities of pore-forming toxins, and VLY-induced epithelial cell membrane
      blebbing in the vaginal mucosa may play a role in the pathogenesis of BV. 

PMID- 24082081
TI  - Chlamydia pneumoniae infection promotes vascular smooth muscle cell migration
      through a Toll-like receptor 2-related signaling pathway.
AB  - The migration of vascular smooth muscle cells (VSMCs) from the media to the
      intima is proposed to be a key event in the development of atherosclerosis.
      Recently, we reported that Chlamydia pneumoniae infection is involved in VSMC
      migration. However, the exact mechanisms for C. pneumoniae infection-induced VSMC
      migration are not yet well elucidated. In this study, we examined the role of the
      Toll-like receptor 2 (TLR2) activation-related signaling pathway in VSMC
      migration induced by C. pneumoniae infection. An Affymetrix-based gene expression
      array was conducted to identify the changes of gene expression in rat primary
      VSMCs (rVSMCs) infected with C. pneumoniae. Both the microarray analysis and
      quantitative real-time reverse transcription (RT)-PCR revealed that TLR2 mRNA
      expression was strongly upregulated 12 h after C. pneumoniae infection. RT-PCR
      and Western blot analysis further showed that the expression levels of TLR2 mRNA
      and protein significantly increased at the different time points after infection.
      Immunocytochemical analysis suggested a TLR2 recruitment to the vicinity of C.
      pneumoniae inclusions. Cell migration assays showed that the TLR2-neutralizing
      antibody could significantly inhibit C. pneumoniae infection-induced rVSMC
      migration. In addition, C. pneumoniae infection stimulated Akt phosphorylation at
      Ser 473, which was obviously suppressed by the PI3K inhibitor LY294002, thereby
      inhibiting rVSMC migration caused by C. pneumoniae infection. Furthermore, both
      the infection-induced Akt phosphorylation and rVSMC migration were suppressed by
      the TLR2-neutralizing antibody. Taken together, these data suggest that C.
      pneumoniae infection can promote VSMC migration possibly through the TLR2-related
      signaling pathway. 

PMID- 24082082
TI  - A single VHH-based toxin-neutralizing agent and an effector antibody protect mice
      against challenge with Shiga toxins 1 and 2.
AB  - Shiga toxin-producing Escherichia coli (STEC) is a major cause of severe food
      borne disease worldwide, and two Shiga toxins, Stx1 and Stx2, are primarily
      responsible for the serious disease consequence, hemolytic-uremic syndrome (HUS).
      Here we report identification of a panel of heavy-chain-only antibody (Ab) V(H)
      (VHH) domains that neutralize Stx1 and/or Stx2 in cell-based assays. VHH
      heterodimer toxin-neutralizing agents containing two linked Stx1-neutralizing
      VHHs or two Stx2-neutralizing VHHs were generally much more potent at Stx
      neutralization than a pool of the two-component monomers tested in cell-based
      assays and in vivo mouse models. We recently reported that clearance of toxins
      can be promoted by coadministering a VHH-based toxin-neutralizing agent with an
      antitag monoclonal antibody (MAb), called the "effector Ab," that indirectly
      decorates each toxin molecule with four Ab molecules. Decoration occurs because
      the Ab binds to a common epitopic tag present at two sites on each of the two VHH
      heterodimer molecules that bind to each toxin molecule. Here we show that
      coadministration of effector Ab substantially improved the efficacy of Stx toxin
      neutralizing agents to prevent death or kidney damage in mice following challenge
      with Stx1 or Stx2. A single toxin-neutralizing agent consisting of a double
      tagged VHH heterotrimer--one Stx1-specific VHH, one Stx2-specific VHH, and one
      Stx1/Stx2 cross-specific VHH--was effective in preventing all symptoms of
      intoxication from Stx1 and Stx2 when coadministered with effector Ab. Overall,
      the availability of simple, defined, recombinant proteins that provide cost
      effective protection against HUS opens up new therapeutic approaches to managing
      disease.

PMID- 24082083
TI  - Hippo signaling disruption and Akt stimulation of ovarian follicles for
      infertility treatment.
AB  - Primary ovarian insufficiency (POI) and polycystic ovarian syndrome are ovarian
      diseases causing infertility. Although there is no effective treatment for POI,
      therapies for polycystic ovarian syndrome include ovarian wedge resection or
      laser drilling to induce follicle growth. Underlying mechanisms for these
      disruptive procedures are unclear. Here, we explored the role of the conserved
      Hippo signaling pathway that serves to maintain optimal size across organs and
      species. We found that fragmentation of murine ovaries promoted actin
      polymerization and disrupted ovarian Hippo signaling, leading to increased
      expression of downstream growth factors, promotion of follicle growth, and the
      generation of mature oocytes. In addition to elucidating mechanisms underlying
      follicle growth elicited by ovarian damage, we further demonstrated additive
      follicle growth when ovarian fragmentation was combined with Akt stimulator
      treatments. We then extended results to treatment of infertility in POI patients
      via disruption of Hippo signaling by fragmenting ovaries followed by Akt
      stimulator treatment and autografting. We successfully promoted follicle growth,
      retrieved mature oocytes, and performed in vitro fertilization. Following embryo
      transfer, a healthy baby was delivered. The ovarian fragmentation-in vitro
      activation approach is not only valuable for treating infertility of POI patients
      but could also be useful for middle-aged infertile women, cancer patients
      undergoing sterilizing treatments, and other conditions of diminished ovarian
      reserve. 

PMID- 24082084
TI  - Loss of metabotropic glutamate receptor 2 escalates alcohol consumption.
AB  - Identification of genes influencing complex traits is hampered by genetic
      heterogeneity, the modest effect size of many alleles, and the likely involvement
      of rare and uncommon alleles. Etiologic complexity can be simplified in model
      organisms. By genomic sequencing, linkage analysis, and functional validation, we
      identified that genetic variation of Grm2, which encodes metabotropic glutamate
      receptor 2 (mGluR2), alters alcohol preference in animal models. Selectively bred
      alcohol-preferring (P) rats are homozygous for a Grm2 stop codon (Grm2 *407) that
      leads to largely uncompensated loss of mGluR2. mGluR2 receptor expression was
      absent, synaptic glutamate transmission was impaired, and expression of genes
      involved in synaptic function was altered. Grm2 *407 was linked to increased
      alcohol consumption and preference in F2 rats generated by intercrossing inbred P
      and nonpreferring rats. Pharmacologic blockade of mGluR2 escalated alcohol self
      administration in Wistar rats, the parental strain of P and nonpreferring rats.
      The causal role of mGluR2 in altered alcohol preference was further supported by
      elevated alcohol consumption in Grm2 (-/-) mice. Together, these data point to
      mGluR2 as an origin of alcohol preference and a potential therapeutic target. 

PMID- 24082085
TI  - Reexposure to nicotine during withdrawal increases the pacemaking activity of
      cholinergic habenular neurons.
AB  - The discovery of genetic variants in the cholinergic receptor nicotinic CHRNA5
      CHRNA3-CHRNB4 gene cluster associated with heavy smoking and higher relapse risk
      has led to the identification of the midbrain habenula-interpeduncular axis as a
      critical relay circuit in the control of nicotine dependence. Although clear
      roles for alpha3, beta4, and alpha5 receptors in nicotine aversion and withdrawal
      have been established, the cellular and molecular mechanisms that participate in
      signaling nicotine use and contribute to relapse have not been identified. Here,
      using translating ribosome affinity purification (TRAP) profiling,
      electrophysiology, and behavior, we demonstrate that cholinergic neurons, but not
      peptidergic neurons, of the medial habenula (MHb) display spontaneous tonic
      firing of 2-10 Hz generated by hyperpolarization-activated cyclic nucleotide
      gated (HCN) pacemaker channels and that infusion of the HCN pacemaker antagonist
      ZD7288 in the habenula precipitates somatic and affective signs of withdrawal.
      Further, we show that a strong, alpha3beta4-dependent increase in firing
      frequency is observed in these pacemaker neurons upon acute exposure to nicotine.
      No change in the basal or nicotine-induced firing was observed in cholinergic MHb
      neurons from mice chronically treated with nicotine. We observe, however, that,
      during withdrawal, reexposure to nicotine doubles the frequency of pacemaking
      activity in these neurons. These findings demonstrate that the pacemaking
      mechanism of cholinergic MHb neurons controls withdrawal, suggesting that the
      heightened nicotine sensitivity of these neurons during withdrawal may contribute
      to smoking relapse. 

PMID- 24082086
TI  - Reversible growth factor dependency and autonomy during murine myelomonocytic
      leukemia induced by oncogenes.
AB  - When murine fetal liver cells were transduced with either of the human acute
      myeloid leukemia fusion oncogenes MLL-ENL or MLL-AF9 and then transplanted to
      irradiated recipient mice, myelomonocyte leukemias rapidly developed from the
      transplanted cells. Analysis of initial events following transduction showed that
      both oncogenes immediately induced a wide range of enhanced proliferative states,
      the most extreme of which could generate continuous lines of cells. Maturation
      defects accompanied the enhanced proliferative states. At all times, the
      transformed cells exhibited complete dependency on hematopoietic growth factors,
      particularly GM-CSF and IL-3. Myelomonocytic leukemic cells from primary or
      transplanted mice formed colonies in semisolid agar. The large majority were
      dependent on hematopoietic growth factors, but a low frequency of autonomous
      colonies was also detected. Unexpectedly, reculture of autonomous leukemic
      colonies generated large numbers of growth factor-dependent clonogenic progeny.
      Similarly, transplanted clonal autonomous leukemic cells produced leukemias
      containing a majority of factor-dependent cells. Conversely, recultures of factor
      dependent colonies in vitro always produced small numbers of autonomous colonies
      among the dependent progeny. The reversible relationship between factor
      dependency and autonomy is surprising because autonomy would have been presumed
      to represent the final, irreversible, leukemic state. 

PMID- 24082087
TI  - Spatial and temporal codes mediate the tactile perception of natural textures.
AB  - When we run our fingers over the surface of an object, we acquire information
      about its microgeometry and material properties. Texture information is widely
      believed to be conveyed in spatial patterns of activation evoked across one of
      three populations of cutaneous mechanoreceptive afferents that innervate the
      fingertips. Here, we record the responses evoked in individual cutaneous
      afferents in Rhesus macaques as we scan a diverse set of natural textures across
      their fingertips using a custom-made rotating drum stimulator. We show that a
      spatial mechanism can only account for the processing of coarse textures.
      Information about most natural textures, however, is conveyed through precise
      temporal spiking patterns in afferent responses, driven by high-frequency skin
      vibrations elicited during scanning. Furthermore, these texture-specific spiking
      patterns predictably dilate or contract in time with changes in scanning speed;
      the systematic effect of speed on neuronal activity suggests that it can be
      reversed to achieve perceptual constancy across speeds. The proposed temporal
      coding mechanism involves converting the fine spatial structure of the surface
      into a temporal spiking pattern, shaped in part by the mechanical properties of
      the skin, and ascribes an additional function to vibration-sensitive
      mechanoreceptive afferents. This temporal mechanism complements the spatial one
      and greatly extends the range of tangible textures. We show that a combination of
      spatial and temporal mechanisms, mediated by all three populations of afferents,
      accounts for perceptual judgments of texture. 

PMID- 24082088
TI  - Hydration dynamics as an intrinsic ruler for refining protein structure at lipid
      membrane interfaces.
AB  - Knowing the topology and location of protein segments at water-membrane
      interfaces is critical for rationalizing their functions, but their
      characterization is challenging under physiological conditions. Here, we debut a
      unique spectroscopic approach by using the hydration dynamics gradient found
      across the phospholipid bilayer as an intrinsic ruler for determining the
      topology, immersion depth, and orientation of protein segments in lipid
      membranes, particularly at water-membrane interfaces. This is achieved through
      the site-specific quantification of translational diffusion of hydration water
      using an emerging tool, (1)H Overhauser dynamic nuclear polarization (ODNP)
      enhanced NMR relaxometry. ODNP confirms that the membrane-bound region of alpha
      synuclein (alphaS), an amyloid protein known to insert an amphipathic alpha-helix
      into negatively charged phospholipid membranes, forms an extended alpha-helix
      parallel to the membrane surface. We extend the current knowledge by showing that
      residues 90-96 of bound alphaS, which is a transition segment that links the
      alpha-helix and the C terminus, adopt a larger loop than an idealized alpha
      helix. The unstructured C terminus gradually threads through the surface
      hydration layers of lipid membranes, with the beginning portion residing within 5
      15 A above the phosphate level, and only the very end of C terminus surveying
      bulk water. Remarkably, the intrinsic hydration dynamics gradient along the
      bilayer normal extends to 20-30 A above the phosphate level, as demonstrated with
      a peripheral membrane protein, annexin B12. ODNP offers the opportunity to reveal
      previously unresolvable structure and location of protein segments well above the
      lipid phosphate, whose structure and dynamics critically contribute to the
      understanding of functional versatility of membrane proteins. 

PMID- 24082089
TI  - Origins of correlated spiking in the mammalian olfactory bulb.
AB  - Mitral/tufted (M/T) cells of the main olfactory bulb transmit odorant information
      to higher brain structures. The relative timing of action potentials across M/T
      cells has been proposed to encode this information and to be critical for the
      activation of downstream neurons. Using ensemble recordings from the mouse
      olfactory bulb in vivo, we measured how correlations between cells are shaped by
      stimulus (odor) identity, common respiratory drive, and other cells' activity.
      The shared respiration cycle is the largest source of correlated firing, but even
      after accounting for all observable factors a residual positive noise correlation
      was observed. Noise correlation was maximal on a ~100-ms timescale and was seen
      only in cells separated by <200 um. This correlation is explained primarily by
      common activity in groups of nearby cells. Thus, M/T-cell correlation principally
      reflects respiratory modulation and sparse, local network connectivity, with odor
      identity accounting for a minor component. 

PMID- 24082090
TI  - Kinematic mental simulations in abduction and deduction.
AB  - We present a theory, and its computer implementation, of how mental simulations
      underlie the abductions of informal algorithms and deductions from these
      algorithms. Three experiments tested the theory's predictions, using an
      environment of a single railway track and a siding. This environment is akin to a
      universal Turing machine, but it is simple enough for nonprogrammers to use.
      Participants solved problems that required use of the siding to rearrange the
      order of cars in a train (experiment 1). Participants abduced and described in
      their own words algorithms that solved such problems for trains of any length,
      and, as the use of simulation predicts, they favored "while-loops" over "for
      loops" in their descriptions (experiment 2). Given descriptions of loops of
      procedures, participants deduced the consequences for given trains of six cars,
      doing so without access to the railway environment (experiment 3). As the theory
      predicts, difficulty in rearranging trains depends on the numbers of moves and
      cars to be moved, whereas in formulating an algorithm and deducing its
      consequences, it depends on the Kolmogorov complexity of the algorithm. Overall,
      the results corroborated the use of a kinematic mental model in creating and
      testing informal algorithms and showed that individuals differ reliably in the
      ability to carry out these tasks. 

PMID- 24082091
TI  - A Hox gene controls lateral line cell migration by regulating chemokine receptor
      expression downstream of Wnt signaling.
AB  - The posterior lateral line primordium in zebrafish provides an amenable model to
      study mechanisms of collective cell migration. The directed migration of the cell
      cluster along the path of Sdf1a chemokine requires two receptors, Cxcr4b and
      Cxcr7b, which are expressed in the leading and trailing part of the primordium,
      respectively. The polarized expression of receptors is regulated by Wnt
      signaling, but downstream players mediating this control remain to be found.
      Here, we show that the Hox homeobox gene Hoxb8a is a critical component that acts
      downstream of the Wnt pathway to coordinate the expression of both chemokine
      receptors. We find that Hoxb8a is expressed in the leading part of the primordium
      and is required for the correct speed and extent of migration. Hoxb8a expression
      is dependent upon Wnt activity and needed both for cxcr4b expression and to
      repress and thus restrict cxcr7b expression to the trailing zone of the
      primordium. In the absence of Wnt activity, overexpressed Hoxb8a is able to
      repress cxcr7b but not up-regulate cxcr4b expression. Together with results from
      expressing dominant activator and repressor constructs, these findings suggest
      that Hoxb8a is induced by and cooperates with Wnt signaling to up-regulate
      cxcr4b, and acts through multiple mechanisms to repress cxcr7b expression. 

PMID- 24082092
TI  - Host and parasite diversity jointly control disease risk in complex communities.
AB  - Host-parasite interactions are embedded within complex communities composed of
      multiple host species and a cryptic assemblage of other parasites. To date,
      however, surprisingly few studies have explored the joint effects of host and
      parasite richness on disease risk, despite growing interest in the diversity
      disease relationship. Here, we combined field surveys and mechanistic experiments
      to test how transmission of the virulent trematode Ribeiroia ondatrae was
      affected by the diversity of both amphibian hosts and coinfecting parasites.
      Within natural wetlands, host and parasite species richness correlated
      positively, consistent with theoretical predictions. Among sites that supported
      Ribeiroia, however, host and parasite richness interacted to negatively affect
      Ribeiroia transmission between its snail and amphibian hosts, particularly in
      species-poor assemblages. In laboratory and outdoor experiments designed to
      decouple the relative contributions of host and parasite diversity, increases in
      host richness decreased Ribeiroia infection by 11-65%. Host richness also tended
      to decrease total infections by other parasite species (four of six instances),
      such that more diverse host assemblages exhibited ~40% fewer infections overall.
      Importantly, parasite richness further reduced both per capita and total
      Ribeiroia infection by 15-20%, possibly owing to intrahost competition among
      coinfecting species. These findings provide evidence that parasitic and free
      living diversity jointly regulate disease risk, help to resolve apparent
      contradictions in the diversity-disease relationship, and emphasize the
      challenges of integrating research on coinfection and host heterogeneity to
      develop a community ecology-based approach to infectious diseases. 

PMID- 24082093
TI  - Organ-specific function of adhesion G protein-coupled receptor GPR126 is domain
      dependent.
AB  - Despite their abundance and multiple functions in a variety of organ systems, the
      function and signaling mechanisms of adhesion G protein-coupled receptors (GPCRs)
      are poorly understood. Adhesion GPCRs possess large N termini containing various
      functional domains. In addition, many of them are autoproteolytically cleaved at
      their GPS sites into an N-terminal fragment (NTF) and C-terminal fragment. Here
      we demonstrate that Gpr126 is expressed in the endocardium during early mouse
      heart development. Gpr126 knockout in mice and knockdown in zebrafish caused
      hypotrabeculation and affected mitochondrial function. Ectopic expression of
      Gpr126-NTF that lacks the GPS motif (NTF(DeltaGPS)) in zebrafish rescued the
      trabeculation but not the previously described myelination phenotype in the
      peripheral nervous system. These data support a model in which the NTF of Gpr126,
      in contrast to the C-terminal fragment, plays an important role in heart
      development. Collectively, our analysis provides a unique example of the
      versatile function and signaling properties of adhesion GPCRs in vertebrates. 

PMID- 24082094
TI  - Genetic topography of brain morphology.
AB  - Animal data show that cortical development is initially patterned by genetic
      gradients largely along three orthogonal axes. We previously reported differences
      in genetic influences on cortical surface area along an anterior-posterior axis
      using neuroimaging data of adult human twins. Here, we demonstrate differences in
      genetic influences on cortical thickness along a dorsal-ventral axis in the same
      cohort. The phenomenon of orthogonal gradations in cortical organization evident
      in different structural and functional properties may originate from genetic
      gradients. Another emerging theme of cortical patterning is that patterns of
      genetic influences recapitulate the spatial topography of the cortex within
      hemispheres. The genetic patterning of both cortical thickness and surface area
      corresponds to cortical functional specializations. Intriguingly, in contrast to
      broad similarities in genetic patterning, two sets of analyses distinguish
      cortical thickness and surface area genetically. First, genetic contributions to
      cortical thickness and surface area are largely distinct; there is very little
      genetic correlation (i.e., shared genetic influences) between them. Second,
      organizing principles among genetically defined regions differ between thickness
      and surface area. Examining the structure of the genetic similarity matrix among
      clusters revealed that, whereas surface area clusters showed great genetic
      proximity with clusters from the same lobe, thickness clusters appear to have
      close genetic relatedness with clusters that have similar maturational timing.
      The discrepancies are in line with evidence that the two traits follow different
      mechanisms in neurodevelopment. Our findings highlight the complexity of genetic
      influences on cortical morphology and provide a glimpse into emerging principles
      of genetic organization of the cortex. 

PMID- 24082095
TI  - Activation of MRTF-A-dependent gene expression with a small molecule promotes
      myofibroblast differentiation and wound healing.
AB  - Myocardin-related transcription factors (MRTFs) regulate cellular contractility
      and motility by associating with serum response factor (SRF) and activating genes
      involved in cytoskeletal dynamics. We reported previously that MRTF-A contributes
      to pathological cardiac remodeling by promoting differentiation of fibroblasts to
      myofibroblasts following myocardial infarction. Here, we show that forced
      expression of MRTF-A in dermal fibroblasts stimulates contraction of a collagen
      matrix, whereas contractility of MRTF-A null fibroblasts is impaired under basal
      conditions and in response to TGF-beta1 stimulation. We also identify an
      isoxazole ring-containing small molecule, previously shown to induce smooth
      muscle alpha-actin gene expression in cardiac progenitor cells, as an agonist of
      myofibroblast differentiation. Isoxazole stimulates myofibroblast differentiation
      via induction of MRTF-A-dependent gene expression. The MRTF-SRF signaling axis is
      activated in response to skin injury, and treatment of dermal wounds with
      isoxazole accelerates wound closure and suppresses the inflammatory response.
      These results reveal an important role for MRTF-SRF signaling in dermal
      myofibroblast differentiation and wound healing and suggest that targeting MRTFs
      pharmacologically may prove useful in treating diseases associated with
      inappropriate myofibroblast activity. 

PMID- 24082096
TI  - Heme impairs the ball-and-chain inactivation of potassium channels.
AB  - Fine-tuned regulation of K(+) channel inactivation enables excitable cells to
      adjust action potential firing. Fast inactivation present in some K(+) channels
      is mediated by the distal N-terminal structure (ball) occluding the ion
      permeation pathway. Here we show that Kv1.4 K(+) channels are potently regulated
      by intracellular free heme; heme binds to the N-terminal inactivation domain and
      thereby impairs the inactivation process, thus enhancing the K(+) current with an
      apparent EC50 value of ~20 nM. Functional studies on channel mutants and
      structural investigations on recombinant inactivation ball domain peptides
      encompassing the first 61 residues of Kv1.4 revealed a heme-responsive binding
      motif involving Cys13:His16 and a secondary histidine at position 35. Heme
      binding to the N-terminal inactivation domain induces a conformational constraint
      that prevents it from reaching its receptor site at the vestibule of the channel
      pore. 

PMID- 24082097
TI  - Mice infer probabilistic models for timing.
AB  - Animals learn both whether and when a reward will occur. Neural models of timing
      posit that animals learn the mean time until reward perturbed by a fixed relative
      uncertainty. Nonetheless, animals can learn to perform actions for reward even in
      highly variable natural environments. Optimal inference in the presence of
      variable information requires probabilistic models, yet it is unclear whether
      animals can infer such models for reward timing. Here, we develop a behavioral
      paradigm in which optimal performance required knowledge of the distribution from
      which reward delays were chosen. We found that mice were able to accurately
      adjust their behavior to the SD of the reward delay distribution. Importantly,
      mice were able to flexibly adjust the amount of prior information used for
      inference according to the moment-by-moment demands of the task. The ability to
      infer probabilistic models for timing may allow mice to adapt to complex and
      dynamic natural environments. 

PMID- 24082099
TI  - Fuglede-Kadison determinant: theme and variations.
AB  - We review the definition of determinants for finite von Neumann algebras, due to
      Fuglede and Kadison [Fuglede B, Kadison R (1952) Ann Math 55:520-530], and a
      generalization for appropriate groups of invertible elements in Banach algebras,
      from a paper by Skandalis and the author (1984). After some discussion of K
      theory and Whitehead torsion, we indicate the relevance of these determinants to
      the study of -torsion in topology. Contents are as follows:1. The classical
      setting. 2. On von Neumann algebras and traces. 3. Fuglede-Kadison determinant
      for finite von Neumann algebras. 4. Motivating question. 5. Brief reminder of K0,
      K1, K1(top), and Bott periodicity. 6. Revisiting the Fuglede-Kadison and other
      determinants. 7. On Whitehead torsion. 8. A few lines on L2-torsion.

PMID- 24082098
TI  - Autoreactive thymic B cells are efficient antigen-presenting cells of cognate
      self-antigens for T cell negative selection.
AB  - The thymus contains a population of B cells that colocalize with dendritic cells
      and medullary thymic epithelial cells in the thymic medulla. The development and
      functional significance of these cells are largely unknown. Using recombination
      activating gene 2 GFP reporter mice along with parabiosis experiments, we
      demonstrate that the vast majority of thymic B cells develop from progenitors
      within the thymus. Thymic B cells express unique phenotypic markers compared with
      peripheral B cells; particularly they express high levels of MHC class II,
      suggesting that they are poised to present self-antigens efficiently. Using Ig
      knock-in and T-cell receptor transgenic mice specific for the self-antigen
      glucose-6-phosphate isomerase, we show that autoreactive thymic B cells serve as
      efficient antigen-presenting cells for T cell negative selection even when they
      are present at low frequencies. Furthermore, the endogenous thymic B-cell
      repertoire also functions in this capacity. These results suggest that developing
      thymic B cells could efficiently capture a broad array of autoantigens through
      their B-cell receptors, presenting peptides derived from those autoantigens to
      developing thymocytes and eliminating cognate T cells. 

PMID- 24082100
TI  - Stigmergy, collective actions, and animal social spacing.
AB  - Collective animal behavior studies have led the way in developing models that
      account for a large number of individuals, but mostly have considered situations
      in which alignment and attraction play a key role, such as in schooling and
      flocking. By quantifying how animals react to one another's presence, when
      interaction is via conspecific avoidance rather than alignment or attraction, we
      present a mechanistic insight that enables us to link individual behavior and
      space use patterns. As animals respond to both current and past positions of
      their neighbors, the assumption that the relative location of individuals is
      statistically and history independent is not tenable, underscoring the
      limitations of traditional space use studies. We move beyond that assumption by
      constructing a framework to analyze spatial segregation of mobile animals when
      neighbor proximity may elicit a retreat, and by linking conspecific encounter
      rate to history-dependent avoidance behavior. Our approach rests on the knowledge
      that animals communicate by modifying the environment in which they live,
      providing a method to analyze social cohesion as stigmergy, a form of mediated
      animal-animal interaction. By considering a population of animals that mark the
      terrain as they move, we predict how the spatiotemporal patterns that emerge
      depend on the degree of stigmergy of the interaction processes. We find in
      particular that nonlocal decision rules may generate a nonmonotonic dependence of
      the animal encounter rate as a function of the tendency to retreat from locations
      recently visited by other conspecifics, which has fundamental implications for
      epidemic disease spread and animal sociality. 

PMID- 24082101
TI  - Discovery of novel chemoeffectors and rational design of Escherichia coli
      chemoreceptor specificity.
AB  - Bacterial chemoreceptors mediate chemotactic responses to diverse stimuli. Here,
      by using an integrated in silico, in vitro, and in vivo approach, we screened a
      large compound library and found eight novel chemoeffectors for the Escherichia
      coli chemoreceptor Tar. Six of the eight new Tar binding compounds induce
      attractant responses, and two of them function as antagonists that can bind Tar
      without inducing downstream signaling. Comparison between the antagonist and
      attractant binding patterns suggests that the key interactions for chemotaxis
      signaling are mediated by the hydrogen bonds formed between a donor group in the
      attractant and the main-chain carbonyls (Y149 and/or Q152) on the alpha4 helix of
      Tar. This molecular insight for signaling is verified by converting an antagonist
      to an attractant when introducing an N-H group into the antagonist to restore the
      hydrogen bond. Similar signal triggering effect by an O-H group is also
      confirmed. Our study suggests that the Tar chemoeffector binding pocket may be
      separated into two functional regions: region I mainly contributes to binding and
      region II contributes to both binding and signaling. This scenario of binding and
      signaling suggests that Tar may be rationally designed to respond to a nonnative
      ligand by altering key residues in region I to strengthen binding with the novel
      ligand while maintaining the key interactions in region II for signaling.
      Following this strategy, we have successfully redesigned Tar to respond to l
      arginine, a basic amino acid that does not have chemotactic effect for WT Tar, by
      two site-specific mutations (R69'E and R73'E). 

PMID- 24082102
TI  - Identification of apolipoprotein D as a cardioprotective gene using a mouse model
      of lethal atherosclerotic coronary artery disease.
AB  - Mice with homozygous null mutations in the HDL receptor (scavenger receptor class
      B, type I, or SR-BI) and apolipoprotein E (apoE) genes [SR-BI/apoE double KO (SR
      BI(-/-)/apoE(-/-) or dKO) mice] spontaneously develop occlusive, atherosclerotic
      coronary artery disease (CAD) and die prematurely (50% mortality at 42 d of age).
      Using microarray mRNA expression profiling, we identified genes whose expression
      in the hearts of dKO mice changed substantially during disease progression [at 21
      d of age (no CAD), 31 d of age (small myocardial infarctions), and 43 d of age
      (extensive myocardial infarctions) vs. CAD-free SR-BI(+/-)/apoE(-/-) controls].
      Expression of most genes that increased >sixfold in dKO hearts at 43 d also
      increased after coronary artery ligation. We examined the influence and potential
      mechanism of action of apolipoprotein D (apoD) whose expression in dKO hearts
      increased 80-fold by 43 d. Analysis of ischemia/reperfusion-induced myocardial
      infarction in both apoD KO mice and wild-type mice with abnormally high plasma
      levels of apoD (adenovirus-mediated hepatic overexpression) established that apoD
      reduces myocardial infarction. There was a correlation of apoD's ability to
      protect primary cultured rat cardiomyocytes from hypoxia/reoxygenation injury
      with its potent ability to inhibit oxidation in a standard antioxidation assay in
      vitro. We conclude that dKO mice represent a useful mouse model of CAD and apoD
      may be part of an intrinsic cardioprotective system, possibly as a consequence of
      its antioxidation activity. 

PMID- 24082103
TI  - Dysregulated NOD2 predisposes SAMP1/YitFc mice to chronic intestinal
      inflammation.
AB  - Nucleotide-binding oligomerization domain-containing 2 (NOD2) is an intracellular
      receptor that plays an essential role in innate immunity as a sensor of a
      component of the bacterial cell wall, muramyl dipeptide (MDP). Crohn's disease
      (CD)-associated NOD2 variants lead to defective innate immune responses,
      including decreased NF-kappaB activation and cytokine production. We report
      herein that SAMP1/YitFc (SAMP) mice, which develop spontaneous CD-like ileitis in
      the absence of NOD2 genetic mutations, fail to respond to MDP administration by
      displaying decreased innate cytokine production and dysregulated NOD2 signaling
      compared with parental AKR control mice. We show that, unlike in other mouse
      strains, in vivo administration of MDP does not prevent dextran sodium sulfate
      induced colitis in SAMP mice and that the abnormal NOD2 response is specific to
      the hematopoietic cellular component. Moreover, we demonstrate that MDP fails to
      enhance intracellular bacterial killing in SAMP mice. These findings shed
      important light on the initiating molecular events underlying CD-like ileitis. 

PMID- 24082104
TI  - Resolving lost herbivore community structure using coprolites of four sympatric
      moa species (Aves: Dinornithiformes).
AB  - Knowledge of extinct herbivore community structuring is essential for assessing
      the wider ecological impacts of Quaternary extinctions and determining
      appropriate taxon substitutes for rewilding. Here, we demonstrate the potential
      for coprolite studies to progress beyond single-species diet reconstructions to
      resolving community-level detail. The moa (Aves: Dinornithiformes) of New Zealand
      are an intensively studied group of nine extinct herbivore species, yet many
      details of their diets and community structuring remain unresolved. We provide
      unique insights into these aspects of moa biology through analyses of a
      multispecies coprolite assemblage from a rock overhang in a montane river valley
      in southern New Zealand. Using ancient DNA (aDNA), we identified 51 coprolites,
      which included specimens from four sympatric moa species. Pollen, plant
      macrofossils, and plant aDNA from the coprolites chronicle the diets and habitat
      preferences of these large avian herbivores during the 400 y before their
      extinction (~1450 AD). We use the coprolite data to develop a paleoecological
      niche model in which moa species were partitioned based on both habitat (forest
      and valley-floor herbfield) and dietary preferences, the latter reflecting
      allometric relationships between body size, digestive efficiency, and nutritional
      requirements. Broad ecological niches occupied by South Island giant moa
      (Dinornis robustus) and upland moa (Megalapteryx didinus) may reflect sexual
      segregation and seasonal variation in habitat use, respectively. Our results show
      that moa lack extant ecological analogs, and their extinction represents an
      irreplaceable loss of function from New Zealand's terrestrial ecosystems. 

PMID- 24082105
TI  - Like cognitive function, decision making across the life span shows profound age
      related changes.
AB  - It has long been known that human cognitive function improves through young
      adulthood and then declines across the later life span. Here we examined how
      decision-making function changes across the life span by measuring risk and
      ambiguity attitudes in the gain and loss domains, as well as choice consistency,
      in an urban cohort ranging in age from 12 to 90 y. We identified several
      important age-related patterns in decision making under uncertainty: First, we
      found that healthy elders between the ages of 65 and 90 were strikingly
      inconsistent in their choices compared with younger subjects. Just as elders show
      profound declines in cognitive function, they also show profound declines in
      choice rationality compared with their younger peers. Second, we found that the
      widely documented phenomenon of ambiguity aversion is specific to the gain domain
      and does not occur in the loss domain, except for a slight effect in older
      adults. Finally, extending an earlier report by our group, we found that risk
      attitudes across the life span show an inverted U-shaped function; both elders
      and adolescents are more risk-averse than their midlife counterparts. Taken
      together, these characterizations of decision-making function across the life
      span in this urban cohort strengthen the conclusions of previous reports
      suggesting a profound impact of aging on cognitive function in this domain. 

PMID- 24082106
TI  - High level of intergenera gene exchange shapes the evolution of haloarchaea in an
      isolated Antarctic lake.
AB  - Deep Lake in Antarctica is a globally isolated, hypersaline system that remains
      liquid at temperatures down to -20  degrees C. By analyzing metagenome data and
      genomes of four isolates we assessed genome variation and patterns of gene
      exchange to learn how the lake community evolved. The lake is completely and
      uniformly dominated by haloarchaea, comprising a hierarchically structured, low
      complexity community that differs greatly to temperate and tropical hypersaline
      environments. The four Deep Lake isolates represent distinct genera (~85% 16S
      rRNA gene similarity and ~73% genome average nucleotide identity) with genomic
      characteristics indicative of niche adaptation, and collectively account for ~72%
      of the cellular community. Network analysis revealed a remarkable level of
      intergenera gene exchange, including the sharing of long contiguous regions (up
      to 35 kb) of high identity (~100%). Although the genomes of closely related
      Halobacterium, Haloquadratum, and Haloarcula (>90% average nucleotide identity)
      shared regions of high identity between species or strains, the four Deep Lake
      isolates were the only distantly related haloarchaea to share long high-identity
      regions. Moreover, the Deep Lake high-identity regions did not match to any other
      hypersaline environment metagenome data. The most abundant species, tADL, appears
      to play a central role in the exchange of insertion sequences, but not the
      exchange of high-identity regions. The genomic characteristics of the four
      haloarchaea are consistent with a lake ecosystem that sustains a high level of
      intergenera gene exchange while selecting for ecotypes that maintain sympatric
      speciation. The peculiarities of this polar system restrict which species can
      grow and provide a tempo and mode for accentuating gene exchange. 

PMID- 24082107
TI  - Translation of pre-spliced RNAs in the nuclear compartment generates peptides for
      the MHC class I pathway.
AB  - The scanning of maturing mRNAs by ribosomes plays a key role in the mRNA quality
      control process. When ribosomes first engage with the newly synthesized mRNA, and
      if peptides are produced, is unclear, however. Here we show that ribosomal
      scanning of prespliced mRNAs occurs in the nuclear compartment, and that this
      event produces peptide substrates for the MHC class I pathway. Inserting
      antigenic peptide sequences in introns that are spliced out before the mRNAs exit
      the nuclear compartment results in an equal amount of antigenic peptide products
      as when the peptides are encoded from the main open reading frame (ORF). Taken
      together with the detection of intron-encoded nascent peptides and RPS6/RPL7
      carrying complexes in the perinucleolar compartment, these results show that
      peptides are produced by a translation event occurring before mRNA splicing. This
      suggests that ribosomes occupy and scan mRNAs early in the mRNA maturation
      process, and suggests a physiological role for nuclear mRNA translation, and also
      helps explain how the immune system tolerates peptides derived from tissue
      specific mRNA splice variants. 

PMID- 24082108
TI  - Graphene quantum point contact transistor for DNA sensing.
AB  - By using the nonequilibrium Green's function technique, we show that the shape of
      the edge, the carrier concentration, and the position and size of a nanopore in
      graphene nanoribbons can strongly affect its electronic conductance as well as
      its sensitivity to external charges. This technique, combined with a self
      consistent Poisson-Boltzmann formalism to account for ion charge screening in
      solution, is able to detect the rotational and positional conformation of a DNA
      strand inside the nanopore. In particular, we show that a graphene membrane with
      quantum point contact geometry exhibits greater electrical sensitivity than a
      uniform armchair geometry provided that the carrier concentration is tuned to
      enhance charge detection. We propose a membrane design that contains an
      electrical gate in a configuration similar to a field-effect transistor for a
      graphene-based DNA sensing device. 

PMID- 24082109
TI  - Globin-coupled heme containing oxygen sensor soluble adenylate cyclase in
      Leishmania prevents cell death during hypoxia.
AB  - Globin and adenylate cyclase play individually numerous crucial roles in
      eukaryotic organisms. Comparison of the amino acid sequences of globins and
      adenylate cyclase from prokaryotic to eukaryotic organisms suggests that they
      share an early common ancestor, even though these proteins execute different
      functions in these two kingdoms. The latest studies of biological signaling
      molecules in both prokaryotic and eukaryotic organisms have discovered a new
      class of heme-containing proteins that act as sensors. The protein of the globin
      family is still unknown in the trypanosomatid parasites, Trypanosome and
      Leishmania. In addition, globin-coupled heme containing adenylate cyclase is
      undescribed in the literature. Here we report a globin-coupled heme containing
      adenylate cyclase (HemAC-Lm) in the unicellular eukaryotic organism Leishmania.
      The protein exhibits spectral properties similar to neuroglobin and cytoglobin.
      Localization studies and activity measurements demonstrate that the protein is
      present in cytosol and oxygen directly stimulates adenylate cyclase activity in
      vivo and in vitro. Gene knockdown and overexpression studies suggest that O2
      dependent cAMP signaling via protein kinase A plays a fundamental role in cell
      survival through suppression of oxidative stress under hypoxia. In addition, the
      enzyme-dependent cAMP generation shows a stimulatory as well as inhibitory role
      in cell proliferation of Leishmania promastigotes during normoxia. Our work
      begins to clarify how O2-dependent cAMP generation by adenylate cyclase is likely
      to function in cellular adaptability under various O2 tensions. 

PMID- 24082110
TI  - Naked mole-rat has increased translational fidelity compared with the mouse, as
      well as a unique 28S ribosomal RNA cleavage.
AB  - The naked mole-rat (Heterocephalus glaber) is a subterranean eusocial rodent with
      a markedly long lifespan and resistance to tumorigenesis. Multiple data implicate
      modulation of protein translation in longevity. Here we report that 28S ribosomal
      RNA (rRNA) of the naked mole-rat is processed into two smaller fragments of
      unequal size. The two breakpoints are located in the 28S rRNA divergent region 6
      and excise a fragment of 263 nt. The excised fragment is unique to the naked mole
      rat rRNA and does not show homology to other genomic regions. Because this hidden
      break site could alter ribosome structure, we investigated whether translation
      rate and amino acid incorporation fidelity were altered. We report that naked
      mole-rat fibroblasts have significantly increased translational fidelity despite
      having comparable translation rates with mouse fibroblasts. Although we cannot
      directly test whether the unique 28S rRNA structure contributes to the increased
      fidelity of translation, we speculate that it may change the folding or dynamics
      of the large ribosomal subunit, altering the rate of GTP hydrolysis and/or
      interaction of the large subunit with tRNA during accommodation, thus affecting
      the fidelity of protein synthesis. In summary, our results show that naked mole
      rat cells produce fewer aberrant proteins, supporting the hypothesis that the
      more stable proteome of the naked mole-rat contributes to its longevity. 

PMID- 24082111
TI  - Inter- and intrasubunit interactions between transmembrane helices in the open
      state of P2X receptor channels.
AB  - P2X receptor channels open in response to the binding of extracellular ATP, a
      property that is essential for purinergic sensory signaling. Apo and ATP-bound X
      ray structures of the detergent-solubilized zebrafish P2X4 receptor provide a
      blueprint for receptor mechanisms but unexpectedly showed large crevices between
      subunits within the transmembrane (TM) domain of the ATP-bound structure. Here we
      investigate both intersubunit and intrasubunit interactions between TM helices of
      P2X receptors in membranes using both computational and functional approaches.
      Our results suggest that intersubunit crevices found in the TM domain of the ATP
      bound crystal structure are not present in membrane-embedded receptors but
      substantiate helix interactions within individual subunits and identify a hot
      spot at the internal end of the pore where both the gating and permeation
      properties of P2X receptors can be tuned. We propose a model for the structure of
      the open state that has stabilizing intersubunit interactions and that is
      compatible with available structural constraints from functional channels in
      membrane environments. 

PMID- 24082112
TI  - A cytochrome P450 regulates a domestication trait in cultivated tomato.
AB  - Domestication of crop plants had effects on human lifestyle and agriculture.
      However, little is known about the underlying molecular mechanisms accompanying
      the changes in fruit appearance as a consequence of selection by early farmers.
      We report the fine mapping and cloning of a tomato (Solanum lycopersicum) fruit
      mass gene encoding the ortholog of KLUH, SlKLUH, a P450 enzyme of the CYP78A
      subfamily. The increase in fruit mass is predominantly the result of enlarged
      pericarp and septum tissues caused by increased cell number in the large fruited
      lines. SlKLUH also modulates plant architecture by regulating number and length
      of the side shoots, and ripening time, and these effects are particularly strong
      in plants that transgenically down-regulate SlKLUH expression carrying fruits of
      a dramatically reduced mass. Association mapping followed by segregation analyses
      revealed that a single nucleotide polymorphism in the promoter of the gene is
      highly associated with fruit mass. This single polymorphism may potentially
      underlie a regulatory mutation resulting in increased SlKLUH expression
      concomitant with increased fruit mass. Our findings suggest that the allele
      giving rise to large fruit arose in the early domesticates of tomato and becoming
      progressively more abundant upon further selections. We also detected association
      of fruit weight with CaKLUH in chile pepper (Capsicum annuum) suggesting that
      selection of the orthologous gene may have occurred independently in a separate
      domestication event. Altogether, our findings shed light on the molecular basis
      of fruit mass, a key domestication trait in tomato and other fruit and vegetable
      crops. 

PMID- 24082113
TI  - Discovery of a selective NaV1.7 inhibitor from centipede venom with analgesic
      efficacy exceeding morphine in rodent pain models.
AB  - Loss-of-function mutations in the human voltage-gated sodium channel NaV1.7
      result in a congenital indifference to pain. Selective inhibitors of NaV1.7 are
      therefore likely to be powerful analgesics for treating a broad range of pain
      conditions. Herein we describe the identification of u-SLPTX-Ssm6a, a unique 46
      residue peptide from centipede venom that potently inhibits NaV1.7 with an IC50
      of ~25 nM. u-SLPTX-Ssm6a has more than 150-fold selectivity for NaV1.7 over all
      other human NaV subtypes, with the exception of NaV1.2, for which the selectivity
      is 32-fold. u-SLPTX-Ssm6a contains three disulfide bonds with a unique
      connectivity pattern, and it has no significant sequence homology with any
      previously characterized peptide or protein. u-SLPTX-Ssm6a proved to be a more
      potent analgesic than morphine in a rodent model of chemical-induced pain, and it
      was equipotent with morphine in rodent models of thermal and acid-induced pain.
      This study establishes u-SPTX-Ssm6a as a promising lead molecule for the
      development of novel analgesics targeting NaV1.7, which might be suitable for
      treating a wide range of human pain pathologies. 

PMID- 24082114
TI  - Paracrine activation of WNT/beta-catenin pathway in uterine leiomyoma stem cells
      promotes tumor growth.
AB  - Uterine leiomyomas are extremely common estrogen and progesterone-dependent
      tumors of the myometrium and cause irregular uterine bleeding, severe anemia, and
      recurrent pregnancy loss in 15-30% of reproductive-age women. Each leiomyoma is
      thought to arise from a single mutated myometrial smooth muscle stem cell.
      Leiomyoma side-population (LMSP) cells comprising 1% of all tumor cells and
      displaying tumor-initiating stem cell characteristics are essential for estrogen-
      and progesterone-dependent in vivo growth of tumors, although they have
      remarkably lower estrogen/progesterone receptor levels than mature myometrial or
      leiomyoma cells. However, how estrogen/progesterone regulates the growth of LMSP
      cells via mature neighboring cells is unknown. Here, we demonstrate a critical
      paracrine role of the wingless-type (WNT)/beta-catenin pathway in
      estrogen/progesterone-dependent tumorigenesis, involving LMSP and differentiated
      myometrial or leiomyoma cells. Estrogen/progesterone treatment of mature
      myometrial cells induced expression of WNT11 and WNT16, which remained
      constitutively elevated in leiomyoma tissues. In LMSP cells cocultured with
      mature myometrial cells, estrogen-progesterone selectively induced nuclear
      translocation of beta-catenin and induced transcriptional activity of its
      heterodimeric partner T-cell factor and their target gene AXIN2, leading to the
      proliferation of LMSP cells. This effect could be blocked by a WNT antagonist.
      Ectopic expression of inhibitor of beta-catenin and T-cell factor 4 in LMSP
      cells, but not in mature leiomyoma cells, blocked the estrogen/progesterone
      dependent growth of human tumors in vivo. We uncovered a paracrine role of the
      WNT/beta-catenin pathway that enables mature myometrial or leiomyoma cells to
      send mitogenic signals to neighboring tissue stem cells in response to estrogen
      and progesterone, leading to the growth of uterine leiomyomas. 

PMID- 24082115
TI  - Damage-induced DNA replication stalling relies on MAPK-activated protein kinase 2
      activity.
AB  - DNA damage can obstruct replication forks, resulting in replicative stress. By
      siRNA screening, we identified kinases involved in the accumulation of
      phosphohistone 2AX (gammaH2AX) upon UV irradiation-induced replication stress.
      Surprisingly, the strongest reduction of phosphohistone 2AX followed knockdown of
      the MAP kinase-activated protein kinase 2 (MK2), a kinase currently implicated in
      p38 stress signaling and G2 arrest. Depletion or inhibition of MK2 also protected
      cells from DNA damage-induced cell death, and mice deficient for MK2 displayed
      decreased apoptosis in the skin upon UV irradiation. Moreover, MK2 activity was
      required for damage response, accumulation of ssDNA, and decreased survival when
      cells were treated with the nucleoside analogue gemcitabine or when the
      checkpoint kinase Chk1 was antagonized. By using DNA fiber assays, we found that
      MK2 inhibition or knockdown rescued DNA replication impaired by gemcitabine or by
      Chk1 inhibition. This rescue strictly depended on translesion DNA polymerases. In
      conclusion, instead of being an unavoidable consequence of DNA damage,
      alterations of replication speed and origin firing depend on MK2-mediated
      signaling. 

PMID- 24082116
TI  - Identification of discrete functional subregions of the human periaqueductal
      gray.
AB  - The midbrain periaqueductal gray (PAG) region is organized into distinct
      subregions that coordinate survival-related responses during threat and stress
      [Bandler R, Keay KA, Floyd N, Price J (2000) Brain Res 53 (1):95-104]. To examine
      PAG function in humans, researchers have relied primarily on functional MRI
      (fMRI), but technological and methodological limitations have prevented
      researchers from localizing responses to different PAG subregions. We used high
      field strength (7-T) fMRI techniques to image the PAG at high resolution (0.75 mm
      isotropic), which was critical for dissociating the PAG from the greater signal
      variability in the aqueduct. Activation while participants were exposed to
      emotionally aversive images segregated into subregions of the PAG along both
      dorsal/ventral and rostral/caudal axes. In the rostral PAG, activity was
      localized to lateral and dorsomedial subregions. In caudal PAG, activity was
      localized to the ventrolateral region. This shifting pattern of activity from
      dorsal to ventral PAG along the rostrocaudal axis mirrors structural and
      functional neurobiological observations in nonhuman animals. Activity in lateral
      and ventrolateral subregions also grouped with distinct emotional experiences
      (e.g., anger and sadness) in a factor analysis, suggesting that each subregion
      participates in distinct functional circuitry. This study establishes the use of
      high-field strength fMRI as a promising technique for revealing the functional
      architecture of the PAG. The techniques developed here also may be extended to
      investigate the functional roles of other brainstem nuclei. 

PMID- 24082117
TI  - Nucleolin mediates nucleosome disruption critical for DNA double-strand break
      repair.
AB  - Recruitment of DNA repair factors and modulation of chromatin structure at sites
      of DNA double-strand breaks (DSBs) is a complex and highly orchestrated process.
      We developed a system that can induce DSBs rapidly at defined endogenous sites in
      mammalian genomes and enables direct assessment of repair and monitoring of
      protein recruitment, egress, and modification at DSBs. The tight regulation of
      the system also permits assessments of relative kinetics and dependencies of
      events associated with cellular responses to DNA breakage. Distinct advantages of
      this system over focus formation/disappearance assays for assessing DSB repair
      are demonstrated. Using ChIP, we found that nucleosomes are partially
      disassembled around DSBs during nonhomologous end-joining repair in G1-arrested
      mammalian cells, characterized by a transient loss of the H2A/H2B histone dimer.
      Nucleolin, a protein with histone chaperone activity, interacts with RAD50 via
      its arginine-glycine rich domain and is recruited to DSBs rapidly in an MRE11
      NBS1-RAD50 complex-dependent manner. Down-regulation of nucleolin abrogates the
      nucleosome disruption, the recruitment of repair factors, and the repair of the
      DSB, demonstrating the functional importance of nucleosome disruption in DSB
      repair and identifying a chromatin-remodeling protein required for the process.
      Interestingly, the nucleosome disruption that occurs during DSB repair in cycling
      cells differs in that both H2A/H2B and H3/H4 histone dimers are removed. This
      complete nucleosome disruption is also dependent on nucleolin and is required for
      recruitment of replication protein A to DSBs, a marker of DSB processing that is
      a requisite for homologous recombination repair. 

PMID- 24082118
TI  - Higher 5-hydroxymethylcytosine identifies immortal DNA strand chromosomes in
      asymmetrically self-renewing distributed stem cells.
AB  - Immortal strands are the targeted chromosomal DNA strands of nonrandom sister
      chromatid segregation, a mitotic chromosome segregation pattern unique to
      asymmetrically self-renewing distributed stem cells (DSCs). By nonrandom
      segregation, immortal DNA strands become the oldest DNA strands in asymmetrically
      self-renewing DSCs. Nonrandom segregation of immortal DNA strands may limit DSC
      mutagenesis, preserve DSC fate, and contribute to DSC aging. The mechanisms
      responsible for specification and maintenance of immortal DNA strands are
      unknown. To discover clues to these mechanisms, we investigated the 5
      methylcytosine and 5-hydroxymethylcytosine (5hmC) content on chromosomes in mouse
      hair follicle DSCs during nonrandom segregation. Although 5-methylcytosine
      content did not differ significantly, the relative content of 5hmC was
      significantly higher in chromosomes containing immortal DNA strands than in
      opposed mitotic chromosomes containing younger mortal DNA strands. The difference
      in relative 5hmC content was caused by the loss of 5hmC from mortal chromosomes.
      These findings implicate higher 5hmC as a specific molecular determinant of
      immortal DNA strand chromosomes. Because 5hmC is an intermediate during DNA
      demethylation, we propose a ten-eleven translocase enzyme mechanism for both the
      specification and maintenance of nonrandomly segregated immortal DNA strands. The
      proposed mechanism reveals a means by which DSCs "know" the generational age of
      immortal DNA strands. The mechanism is supported by molecular expression data and
      accounts for the selection of newly replicated DNA strands when nonrandom
      segregation is initiated. These mechanistic insights also provide a possible
      basis for another characteristic property of immortal DNA strands, their guanine
      ribonucleotide dependency. 

PMID- 24082119
TI  - Physics-based method to validate and repair flaws in protein structures.
AB  - A method that makes use of information provided by the combination of
      (13)C(alpha) and (13)C(beta) chemical shifts, computed at the density functional
      level of theory, enables one to (i) validate, at the residue level, conformations
      of proteins and detect backbone or side-chain flaws by taking into account an
      ensemble average of chemical shifts over all of the conformations used to
      represent a protein, with a sensitivity of ~90%; and (ii) provide a set of
      (chi1/chi2) torsional angles that leads to optimal agreement between the observed
      and computed (13)C(alpha) and (13)C(beta) chemical shifts. The method has been
      incorporated into the CheShift-2 protein validation Web server. To test the
      reliability of the provided set of (chi1/chi2) torsional angles, the side chains
      of all reported conformations of five NMR-determined protein models were refined
      by a simple routine, without using NOE-based distance restraints. The refinement
      of each of these five proteins leads to optimal agreement between the observed
      and computed (13)C(alpha) and (13)C(beta) chemical shifts for ~94% of the flaws,
      on average, without introducing a significantly large number of violations of the
      NOE-based distance restraints for a distance range <= 0.5 , in which the largest
      number of distance violations occurs. The results of this work suggest that use
      of the provided set of (chi1/chi2) torsional angles together with other
      observables, such as NOEs, should lead to a fast and accurate refinement of the
      side-chain conformations of protein models. 

PMID- 24082120
TI  - Tracking the establishment of local endemic populations of an emergent enteric
      pathogen.
AB  - Shigella sonnei is a human-adapted pathogen that is emerging globally as the
      dominant agent of bacterial dysentery. To investigate local establishment, we
      sequenced the genomes of 263 Vietnamese S. sonnei isolated over 15 y. Our data
      show that S. sonnei was introduced into Vietnam in the 1980s and has undergone
      localized clonal expansion, punctuated by genomic fixation events through
      periodic selective sweeps. We uncover geographical spread, spatially restricted
      frontier populations, and convergent evolution through local gene pool sampling.
      This work provides a unique, high-resolution insight into the microevolution of a
      pioneering human pathogen during its establishment in a new host population. 

PMID- 24082121
TI  - Essential role of stress hormone signaling in cardiomyocytes for the prevention
      of heart disease.
AB  - Heart failure is a leading cause of death in humans, and stress is increasingly
      associated with adverse cardiac outcomes. Glucocorticoids are primary stress
      hormones, but their direct role in cardiovascular health and disease is poorly
      understood. To determine the in vivo function of glucocorticoid signaling in the
      heart, we generated mice with cardiomyocyte-specific deletion of the
      glucocorticoid receptor (GR). These mice are born at the expected Mendelian
      ratio, but die prematurely from spontaneous cardiovascular disease. By 3 mo of
      age, mice deficient in cardiomyocyte GR display a marked reduction in left
      ventricular systolic function, as evidenced by decreases in ejection fraction and
      fractional shortening. Heart weight and left ventricular mass are elevated, and
      histology revealed cardiac hypertrophy without fibrosis. Removal of endogenous
      glucocorticoids and mineralocorticoids neither augmented nor lessened the
      hypertrophic response. Global gene expression analysis of knockout hearts before
      pathology onset revealed aberrant regulation of a large cohort of genes
      associated with cardiovascular disease as well as unique disease genes associated
      with inflammatory processes. Genes important for maintaining cardiac
      contractility, repressing cardiac hypertrophy, promoting cardiomyocyte survival,
      and inhibiting inflammation had decreased expression in the GR-deficient hearts.
      These findings demonstrate that a deficiency in cardiomyocyte glucocorticoid
      signaling leads to spontaneous cardiac hypertrophy, heart failure, and death,
      revealing an obligate role for GR in maintaining normal cardiovascular function.
      Moreover, our findings suggest that selective activation of cardiomyocyte GR may
      represent an approach for the prevention of heart disease. 

PMID- 24082122
TI  - Structure-function analysis of ribonucleotide bypass by B family DNA replicases.
AB  - Ribonucleotides are frequently incorporated into DNA during replication, they are
      normally removed, and failure to remove them results in replication stress. This
      stress correlates with DNA polymerase (Pol) stalling during bypass of
      ribonucleotides in DNA templates. Here we demonstrate that stalling by yeast
      replicative Pols delta and epsilon increases as the number of consecutive
      template ribonucleotides increases from one to four. The homologous bacteriophage
      RB69 Pol also stalls during ribonucleotide bypass, with a pattern most similar to
      that of Pol epsilon. Crystal structures of an exonuclease-deficient variant of
      RB69 Pol corresponding to multiple steps in single ribonucleotide bypass reveal
      that increased stalling is associated with displacement of Tyr391 and an
      unpreferred C2'-endo conformation for the ribose. Even less efficient bypass of
      two consecutive ribonucleotides in DNA correlates with similar movements of
      Tyr391 and displacement of one of the ribonucleotides along with the primer
      strand DNA backbone. These structure-function studies have implications for
      cellular signaling by ribonucleotides, and they may be relevant to replication
      stress in cells defective in ribonucleotide excision repair, including humans
      suffering from autoimmune disease associated with RNase H2 defects. 

PMID- 24082123
TI  - CRL4A-FBXW5-mediated degradation of DLC1 Rho GTPase-activating protein tumor
      suppressor promotes non-small cell lung cancer cell growth.
AB  - DLC1 encodes a RhoA GTPase-activating protein and tumor suppressor lost in cancer
      by genomic deletion or epigenetic silencing and loss of DLC1 gene transcription.
      We unexpectedly identified non-small cell lung cancer (NSCLC) cell lines and
      tumor tissue that expressed DLC1 mRNA yet lacked DLC1 protein expression. We
      determined that DLC1 was ubiquitinated and degraded by cullin 4A-RING ubiquitin
      ligase (CRL4A) complex interaction with DDB1 and the FBXW5 substrate receptor.
      siRNA-mediated suppression of cullin 4A, DDB1, or FBXW5 expression restored DLC1
      protein expression in NSCLC cell lines. FBXW5 suppression-induced DLC1
      reexpression was associated with a reduction in the levels of activated RhoA-GTP
      and in RhoA effector signaling. Finally, FBXW5 suppression caused a DLC1
      dependent decrease in NSCLC anchorage-dependent and -independent proliferation.
      In summary, we identify a posttranslational mechanism for loss of DLC1 and a
      linkage between CRL4A-FBXW5-associated oncogenesis and regulation of RhoA
      signaling. 

PMID- 24082124
TI  - Hijacking of leguminous nodulation signaling by the rhizobial type III secretion
      system.
AB  - Root-nodule symbiosis between leguminous plants and nitrogen-fixing bacteria
      (rhizobia) involves molecular communication between the two partners. Key
      components for the establishment of symbiosis are rhizobium-derived
      lipochitooligosaccharides (Nod factors; NFs) and their leguminous receptors
      (NFRs) that initiate nodule development and bacterial entry. Here we demonstrate
      that the soybean microsymbiont Bradyrhizobium elkanii uses the type III secretion
      system (T3SS), which is known for its delivery of virulence factors by pathogenic
      bacteria, to promote symbiosis. Intriguingly, wild-type B. elkanii, but not the
      T3SS-deficient mutant, was able to form nitrogen-fixing nodules on soybean nfr
      mutant En1282. Furthermore, even the NF-deficient B. elkanii mutant induced
      nodules unless T3SS genes were mutated. Transcriptional analysis revealed that
      expression of the soybean nodulation-specific genes ENOD40 and NIN was increased
      in the roots of En1282 inoculated with B. elkanii but not with its T3SS mutant,
      suggesting that T3SS activates host nodulation signaling by bypassing NF
      recognition. Root-hair curling and infection threads were not observed in the
      roots of En1282 inoculated with B. elkanii, indicating that T3SS is involved in
      crack entry or intercellular infection. These findings suggest that B. elkanii
      has adopted a pathogenic system for activating host symbiosis signaling to
      promote its infection. 

PMID- 24082125
TI  - Oxygen dynamics in the aftermath of the Great Oxidation of Earth's atmosphere.
AB  - The oxygen content of Earth's atmosphere has varied greatly through time,
      progressing from exceptionally low levels before about 2.3 billion years ago, to
      much higher levels afterward. In the absence of better information, we usually
      view the progress in Earth's oxygenation as a series of steps followed by periods
      of relative stasis. In contrast to this view, and as reported here, a dynamic
      evolution of Earth's oxygenation is recorded in ancient sediments from the
      Republic of Gabon from between about 2,150 and 2,080 million years ago. The
      oldest sediments in this sequence were deposited in well-oxygenated deep waters
      whereas the youngest were deposited in euxinic waters, which were globally
      extensive. These fluctuations in oxygenation were likely driven by the comings
      and goings of the Lomagundi carbon isotope excursion, the longest-lived positive
      delta(13)C excursion in Earth history, generating a huge oxygen source to the
      atmosphere. As the Lomagundi event waned, the oxygen source became a net oxygen
      sink as Lomagundi organic matter became oxidized, driving oxygen to low levels;
      this state may have persisted for 200 million years. 

PMID- 24082126
TI  - Stratospheric water vapor feedback.
AB  - We show here that stratospheric water vapor variations play an important role in
      the evolution of our climate. This comes from analysis of observations showing
      that stratospheric water vapor increases with tropospheric temperature, implying
      the existence of a stratospheric water vapor feedback. We estimate the strength
      of this feedback in a chemistry-climate model to be +0.3 W/(m(2)?K), which would
      be a significant contributor to the overall climate sensitivity. One-third of
      this feedback comes from increases in water vapor entering the stratosphere
      through the tropical tropopause layer, with the rest coming from increases in
      water vapor entering through the extratropical tropopause. 

PMID- 24082127
TI  - The LIM homeobox gene Isl1 is required for the correct development of the
      striatonigral pathway in the mouse.
AB  - The mammalian striatum controls the output of the basal ganglia via two distinct
      efferent pathways, the direct (i.e., striatonigral) and the indirect (i.e.,
      striatopallidal) pathways. The LIM homeodomain transcription factor Islet1 (Isl1)
      is expressed in a subpopulation of striatal progenitors; however, its specific
      role in striatal development remains unknown. Our genetic fate-mapping results
      show that Isl1-expressing progenitors give rise to striatal neurons belonging to
      the striatonigral pathway. Conditional inactivation of Isl1 in the telencephalon
      resulted in a smaller striatum with fewer striatonigral neurons and reduced
      projections to the substantia nigra. Additionally, conditional inactivation in
      the ventral forebrain (including both the telencephalon and diencephalon)
      revealed a unique role for Isl1 in diencephalic cells bordering the internal
      capsule for the normal development of the striatonigral pathway involving
      PlexinD1-Semaphorin 3e (Sema3e) signaling. Finally, Isl1 conditional mutants
      displayed a hyperlocomotion phenotype, and their locomotor response to
      psychostimulants was significantly blunted, indicating that the alterations in
      basal ganglia circuitry contribute to these mutant behaviors. 

PMID- 24082128
TI  - Peptide transporter DtpA has two alternate conformations, one of which is
      promoted by inhibitor binding.
AB  - Peptide transporters (PTRs) of the large PTR family facilitate the uptake of di-
      and tripeptides to provide cells with amino acids for protein synthesis and for
      metabolic intermediates. Although several PTRs have been structurally and
      functionally characterized, how drugs modulate peptide transport remains unclear.
      To obtain insight into this mechanism, we characterize inhibitor binding to the
      Escherichia coli PTR dipeptide and tripeptide permease A (DtpA), which shows
      substrate specificities similar to its human homolog hPEPT1. After demonstrating
      that Lys[Z-NO2]-Val, the strongest inhibitor of hPEPT1, also acts as a high
      affinity inhibitor for DtpA, we used single-molecule force spectroscopy to
      localize the structural segments stabilizing the peptide transporter and
      investigated which of these structural segments change stability upon inhibitor
      binding. This characterization was done with DtpA embedded in the lipid membrane
      and exposed to physiologically relevant conditions. In the unbound state, DtpA
      adopts two main alternate conformations in which transmembrane alpha-helix (TMH)
      2 is either stabilized (in ~43% of DtpA molecules) or not (in ~57% of DtpA
      molecules). The two conformations are understood to represent the inward- and
      outward-facing conformational states of the transporter. With increasing
      inhibitor concentration, the conformation characterized by a stabilized TMH 2
      becomes increasingly prevalent, reaching ~92% at saturation. Our measurements
      further suggest that Lys[Z-NO2]-Val interacts with discrete residues in TMH 2
      that are important for ligand binding and substrate affinity. These interactions
      in turn stabilize TMH 2, thereby promoting the inhibited conformation of DtpA. 

PMID- 24082129
TI  - Prognostic significance of 2-hydroxyglutarate levels in acute myeloid leukemia in
      China.
AB  - The 2-hydroxyglutarate (2-HG) has been reported to result from mutations of
      isocitrate dehydrogenase 1 and 2 (IDH1 and IDH2) genes and to function as an
      "oncometabolite." To evaluate the clinical significance of serum 2-HG levels in
      hematologic malignancies, acute myeloid leukemia (AML) in particular, we analyzed
      this metabolite in distinct types of human leukemia and lymphoma and established
      the range of serum 2-HG in appropriate normal control individuals by using gas
      chromatograph-time-of-flight mass spectrometry. Aberrant serum 2-HG pattern was
      detected in the multicenter group of AML, with 62 of 367 (17%) patients having 2
      HG levels above the cutoff value (2.01, log2-transformed from 4.03 MUg/mL).
      IDH1/2 mutations occurred in 27 of 31 (87%) AML cases with very high 2-HG, but
      were observed only in 9 of 31 (29%) patients with moderately high 2-HG,
      suggesting other genetic or biochemical events may exist in causing 2-HG
      elevation. Indeed, glutamine-related metabolites exhibited a pattern in favor of
      2-HG synthesis in the high 2-HG group. In AML patients with cytogenetically
      normal AML (n = 234), high 2-HG represented a negative prognostic factor in both
      overall survival and event-free survival. Univariate and multivariate analyses
      confirmed high serum 2-HG as a strong prognostic predictor independent of other
      clinical and molecular features. We also demonstrated distinct gene
      expression/DNA methylation profiles in AML blasts with high 2-HG compared with
      those with normal ones, supporting a role that 2-HG plays in leukemogenesis. 

PMID- 24082130
TI  - Selecting antagonistic antibodies that control differentiation through inducible
      expression in embryonic stem cells.
AB  - Antibodies that modulate receptor function have great untapped potential in the
      control of stem cell differentiation. In contrast to many natural ligands,
      antibodies are stable, exquisitely specific, and are unaffected by the regulatory
      mechanisms that act on natural ligands. Here we describe an innovative system for
      identifying such antibodies by introducing and expressing antibody gene
      populations in ES cells. Following induced antibody expression and secretion,
      changes in differentiation outcomes of individual antibody-expressing ES clones
      are monitored using lineage-specific gene expression to identify clones that
      encode and express signal-modifying antibodies. This in-cell expression and
      reporting system was exemplified by generating blocking antibodies to FGF4 and
      its receptor FGFR1beta, identified through delayed onset of ES cell
      differentiation. Functionality of the selected antibodies was confirmed by
      addition of exogenous antibodies to three different ES reporter cell lines, where
      retained expression of pluripotency markers Oct4, Nanog, and Rex1 was observed.
      This work demonstrates the potential for discovery and utility of functional
      antibodies in stem cell differentiation. This work is also unique in constituting
      an example of ES cells carrying an inducible antibody that causes a functional
      protein "knock-down" and allows temporal control of stable signaling components
      at the protein level. 

PMID- 24082131
TI  - Epigenomic programming contributes to the genomic drift evolution of the F-Box
      protein superfamily in Arabidopsis.
AB  - Comparisons within expanding sequence databases have revealed a dynamic interplay
      among genomic and epigenomic forces in driving plant evolution. Such forces are
      especially obvious within the F-Box (FBX) superfamily, one of the largest and
      most polymorphic gene families in land plants, where its frequent lineage
      specific expansions and contractions provide an excellent model to assess how
      genetic variation impacted gene function before and after speciation. Previous
      phylogenetic comparisons based on orthology, diversity, and expression patterns
      identified three plant FBX groups--Common, Lineage-Specific, and Pseudo(genized)-
      whose emergences are consistent with genomic drift evolution. Here, we examined
      this variance within Arabidopsis thaliana by evaluating SNPs for all 877 FBX loci
      from 432 naturally occurring accessions and their relationships to variations in
      natural selection, expression, and DNA/histone methylation. In line with their
      phenotypic importance, Common FBX loci have low polymorphism but high deleterious
      mutation rates indicative of stringent functional constraints. In contrast, the
      Lineage-Specific and Pseudo groups are enriched in genes with basal expression
      and higher SNP density and more correlated with methylation marks (RNA-directed
      DNA methylation and histone H3K27 trimethylation) that promote transcriptional
      silencing. Taken together, we propose that reversible epigenomic modifications
      helped shape FBX gene evolution by transcriptionally suppressing the adverse
      effects of gene dosage imbalance and harmful FBX alleles that arise during
      genomic drift, while simultaneously allowing innovations to emerge through
      epigenomic reprogramming.

PMID- 24082132
TI  - Source of the great A.D. 1257 mystery eruption unveiled, Samalas volcano, Rinjani
      Volcanic Complex, Indonesia.
AB  - Polar ice core records attest to a colossal volcanic eruption that took place ca.
      A.D. 1257 or 1258, most probably in the tropics. Estimates based on sulfate
      deposition in these records suggest that it yielded the largest volcanic sulfur
      release to the stratosphere of the past 7,000 y. Tree rings, medieval chronicles,
      and computational models corroborate the expected worldwide atmospheric and
      climatic effects of this eruption. However, until now there has been no
      convincing candidate for the mid-13th century "mystery eruption." Drawing upon
      compelling evidence from stratigraphic and geomorphic data, physical volcanology,
      radiocarbon dating, tephra geochemistry, and chronicles, we argue the source of
      this long-sought eruption is the Samalas volcano, adjacent to Mount Rinjani on
      Lombok Island, Indonesia. At least 40 km(3) (dense-rock equivalent) of tephra
      were deposited and the eruption column reached an altitude of up to 43 km. Three
      principal pumice fallout deposits mantle the region and thick pyroclastic flow
      deposits are found at the coast, 25 km from source. With an estimated magnitude
      of 7, this event ranks among the largest Holocene explosive eruptions.
      Radiocarbon dates on charcoal are consistent with a mid-13th century eruption. In
      addition, glass geochemistry of the associated pumice deposits matches that of
      shards found in both Arctic and Antarctic ice cores, providing compelling
      evidence to link the prominent A.D. 1258/1259 ice core sulfate spike to Samalas.
      We further constrain the timing of the mystery eruption based on tephra dispersal
      and historical records, suggesting it occurred between May and October A.D. 1257.

PMID- 24082133
TI  - Mutation in the RmbetaAOR gene is associated with amitraz resistance in the
      cattle tick Rhipicephalus microplus.
AB  - We aimed to describe the evolution of resistance to amitraz in Rhipicephalus
      microplus in the field and to test the association between amitraz resistance and
      the frequency of a mutation in the beta-adrenergic octopamine receptor gene
      (RmbetaAOR). We established six populations of Rhipicephalus microplus ticks in
      similar paddocks by the admixture of ticks from strains known to be susceptible
      and resistant to amitraz and synthetic pyrethroids. Each population was managed
      using one of three acaricide treatment regimes: always amitraz, always spinosad,
      or rotation between amitraz and spinosad. We used microsatellites to elucidate
      population structure over time, an SNP in the para-sodium channel gene previously
      demonstrated to confer resistance to synthetic pyrethroids to quantify changes in
      resistance to synthetic pyrethroids over time, and a nonsynonymous SNP in the
      RmbetaAOR, a gene that we proposed to confer resistance to amitraz, to determine
      whether selection with amitraz increased the frequency of this mutation. The
      study showed panmixia of the two strains and that selection of ticks with amitraz
      increased the frequency of the RmbetaAOR mutation while increasing the prevalence
      of amitraz-resistance. We conclude that polymorphisms in the RmbetaAOR gene are
      likely to confer resistance to amitraz. 

PMID- 24082134
TI  - Photogeneration of hydrogen from water using CdSe nanocrystals demonstrating the
      importance of surface exchange.
AB  - Unique tripodal S-donor capping agents with an attached carboxylate are found to
      bind tightly to the surface of CdSe nanocrystals (NCs), making the latter water
      soluble. Unlike that in similarly solubilized CdSe NCs with one-sulfur or two
      sulfur capping agents, dissociation from the NC surface is greatly reduced. The
      impact of this behavior is seen in the photochemical generation of H2 in which
      the CdSe NCs function as the light absorber with metal complexes in aqueous
      solution as the H2-forming catalyst and ascorbic acid as the electron donor
      source. This precious-metal-free system for H2 generation from water using
      [Co(bdt)2](-) (bdt, benzene-1,2-dithiolate) as the catalyst exhibits excellent
      activity with a quantum yield for H2 formation of 24% at 520 nm light and
      durability with >300,000 turnovers relative to catalyst in 60 h. 

PMID- 24082135
TI  - In vitro evolution of alpha-hemolysin using a liposome display.
AB  - In vitro methods have enabled the rapid and efficient evolution of proteins and
      successful generation of novel and highly functional proteins. However, the
      available methods consider only globular proteins (e.g., antibodies, enzymes) and
      not membrane proteins despite the biological and pharmaceutical importance of the
      latter. In this study, we report the development of a method called liposome
      display that can evolve the properties of membrane proteins entirely in vitro.
      This method, which involves in vitro protein synthesis inside liposomes, which
      are cell-sized phospholipid vesicles, was applied to the pore-forming activity of
      alpha-hemolysin, a membrane protein derived from Staphylococcus aureus. The
      obtained alpha-hemolysin mutant possessed only two point mutations but exhibited
      a 30-fold increase in its pore-forming activity compared with the WT. Given the
      ability to synthesize various membrane proteins and modify protein synthesis and
      functional screening conditions, this method will allow for the rapid and
      efficient evolution of a wide range of membrane proteins. 

PMID- 24082136
TI  - Defining efficient enzyme-cofactor pairs for bioorthogonal profiling of protein
      methylation.
AB  - Protein methyltransferase (PMT)-mediated posttranslational modification of
      histone and nonhistone substrates modulates stability, localization, and
      interacting partners of target proteins in diverse cellular contexts. These
      events play critical roles in normal biological processes and are frequently
      deregulated in human diseases. In the course of identifying substrates of
      individual PMTs, bioorthogonal profiling of protein methylation (BPPM) has
      demonstrated its merits. In this approach, specific PMTs are engineered to
      process S-adenosyl-L-methionine (SAM) analogs as cofactor surrogates and label
      their substrates with distinct chemical modifications for target elucidation.
      Despite the proof-of-concept advancement of BPPM, few efforts have been made to
      explore its generality. With two cancer-relevant PMTs, EuHMT1 (GLP1/KMT1D) and
      EuHMT2 (G9a/KMT1C), as models, we defined the key structural features of
      engineered PMTs and matched SAM analogs that can render the orthogonal enzyme
      cofactor pairs for efficient catalysis. Here we have demonstrated that the
      presence of sulfonium-beta-sp(2) carbon and flexible, medium-sized sulfonium
      delta-substituents are crucial for SAM analogs as BPPM reagents. The bulky
      cofactors can be accommodated by tailoring the conserved Y1211/Y1154 residues and
      nearby hydrophobic cavities of EuHMT1/2. Profiling proteome-wide substrates with
      BPPM allowed identification of >500 targets of EuHMT1/2 with representative
      targets validated using native EuHMT1/2 and SAM. This finding indicates that
      EuHMT1/2 may regulate many cellular events previously unrecognized to be
      modulated by methylation. The present work, therefore, paves the way to a broader
      application of the BPPM technology to profile methylomes of diverse PMTs and
      elucidate their downstream functions. 

PMID- 24082137
TI  - The gated induction system of a systemic floral inhibitor, antiflorigen,
      determines obligate short-day flowering in chrysanthemums.
AB  - Photoperiodic floral induction has had a significant impact on the agricultural
      and horticultural industries. Changes in day length are perceived in leaves,
      which synthesize systemic flowering inducers (florigens) and inhibitors
      (antiflorigens) that determine floral initiation at the shoot apex. Recently,
      FLOWERING LOCUS T (FT) was found to be a florigen; however, the identity of the
      corresponding antiflorigen remains to be elucidated. Here, we report the
      identification of an antiflorigen gene, Anti-florigenic FT/TFL1 family protein
      (AFT), from a wild chrysanthemum (Chrysanthemum seticuspe) whose expression is
      mainly induced in leaves under noninductive conditions. Gain- and loss-of
      function analyses demonstrated that CsAFT acts systemically to inhibit flowering
      and plays a predominant role in the obligate photoperiodic response. A transient
      gene expression assay indicated that CsAFT inhibits flowering by directly
      antagonizing the flower-inductive activity of CsFTL3, a C. seticuspe ortholog of
      FT, through interaction with CsFDL1, a basic leucine zipper (bZIP) transcription
      factor FD homolog of Arabidopsis. Induction of CsAFT was triggered by the
      coincidence of phytochrome signals with the photosensitive phase set by the dusk
      signal; flowering occurred only when night length exceeded the photosensitive
      phase for CsAFT induction. Thus, the gated antiflorigen production system, a
      phytochrome-mediated response to light, determines obligate photoperiodic
      flowering response in chrysanthemums, which enables their year-round commercial
      production by artificial lighting. 

PMID- 24082138
TI  - Computational study of the activated O(H) state in the catalytic mechanism of
      cytochrome c oxidase.
AB  - Complex IV in the respiratory chain of mitochondria and bacteria catalyzes
      reduction of molecular oxygen to water, and conserves much of the liberated free
      energy as an electrochemical proton gradient, which is used for the synthesis of
      ATP. Photochemical electron injection experiments have shown that reduction of
      the ferric/cupric state of the enzyme's binuclear heme a3/CuB center is coupled
      to proton pumping across the membrane, but only if oxidation of the reduced
      enzyme by O2 immediately precedes electron injection. In contrast, reduction of
      the binuclear center in the "as-isolated" ferric/cupric enzyme is sluggish and
      without linkage to proton translocation. During turnover, the binuclear center
      apparently shuttles via a metastable but activated ferric/cupric state (O(H)),
      which may decay into a more stable catalytically incompetent form (O) in the
      absence of electron donors. The structural basis for the difference between these
      two states has remained elusive, and is addressed here using computational
      methodology. The results support the notion that CuB[II] is either three
      coordinated in the O(H) state or shares an OH(-) ligand with heme a3 in a
      strained MU-hydroxo structure. Relaxation to state O is initiated by hydration of
      the binuclear site. The redox potential of CuB is expected, and found by density
      functional theory calculations, to be substantially higher in the O(H) state than
      in state O. Our calculations also suggest that the neutral radical form of the
      cross-linked tyrosine in the binuclear site may be more significant in the
      catalytic cycle than suspected so far.

PMID- 24082139
TI  - Personalized genomic disease risk of volunteers.
AB  - Next-generation sequencing (NGS) is commonly used for researching the causes of
      genetic disorders. However, its usefulness in clinical practice for medical
      diagnosis is in early development. In this report, we demonstrate the value of
      NGS for genetic risk assessment and evaluate the limitations and barriers for the
      adoption of this technology into medical practice. We performed whole exome
      sequencing (WES) on 81 volunteers, and for each volunteer, we requested personal
      medical histories, constructed a three-generation pedigree, and required their
      participation in a comprehensive educational program. We limited our clinical
      reporting to disease risks based on only rare damaging mutations and known
      pathogenic variations in genes previously reported to be associated with human
      disorders. We identified 271 recessive risk alleles (214 genes), 126 dominant
      risk alleles (101 genes), and 3 X-recessive risk alleles (3 genes). We linked
      personal disease histories with causative disease genes in 18 volunteers.
      Furthermore, by incorporating family histories into our genetic analyses, we
      identified an additional five heritable diseases. Traditional genetic counseling
      and disease education were provided in verbal and written reports to all
      volunteers. Our report demonstrates that when genome results are carefully
      interpreted and integrated with an individual's medical records and pedigree
      data, NGS is a valuable diagnostic tool for genetic disease risk. 

PMID- 24082142
TI  - Prototype of an intertwined secondary-metabolite supercluster.
AB  - The hallmark trait of fungal secondary-metabolite gene clusters is well
      established, consisting of contiguous enzymatic and often regulatory gene(s)
      devoted to the production of a metabolite of a specific chemical class.
      Unexpectedly, we have found a deviation from this motif in a subtelomeric region
      of Aspergillus fumigatus. This region, under the control of the master regulator
      of secondary metabolism, LaeA, contains, in its entirety, the genetic machinery
      for three natural products (fumitremorgin, fumagillin, and pseurotin), where
      genes for fumagillin and pseurotin are physically intertwined in a single
      supercluster. Deletions of 29 adjoining genes revealed that fumagillin and
      pseurotin are coregulated by the supercluster-embedded regulatory gene with
      biosynthetic genes belonging to one of the two metabolic pathways in a
      noncontiguous manner. Comparative genomics indicates the fumagillin/pseurotin
      supercluster is maintained in a rapidly evolving region of diverse fungal
      genomes. This blended design confounds predictions from established secondary
      metabolite cluster search algorithms and provides an expanded view of natural
      product evolution. 

PMID- 24082141
TI  - p21-mediated RNR2 repression restricts HIV-1 replication in macrophages by
      inhibiting dNTP biosynthesis pathway.
AB  - Macrophages are a major target cell for HIV-1, and their infection contributes to
      HIV pathogenesis. We have previously shown that the cyclin-dependent kinase
      inhibitor p21 inhibits the replication of HIV-1 and other primate lentiviruses in
      human monocyte-derived macrophages by impairing reverse transcription of the
      viral genome. In the attempt to understand the p21-mediated restriction
      mechanisms, we found that p21 impairs HIV-1 and simian immunodeficiency virus
      (SIV)mac reverse transcription in macrophages by reducing the intracellular
      deoxyribonucleotide (dNTP) pool to levels below those required for viral cDNA
      synthesis by a SAM domain and HD domain-containing protein 1 (SAMHD1)-independent
      pathway. We found that p21 blocks dNTP biosynthesis by down-regulating the
      expression of the RNR2 subunit of ribonucleotide reductase, an enzyme essential
      for the reduction of ribonucleotides to dNTP. p21 inhibits RNR2 transcription by
      repressing E2F1 transcription factor, its transcriptional activator. Our findings
      unravel a cellular pathway that restricts HIV-1 and other primate lentiviruses by
      affecting dNTP synthesis, thereby pointing to new potential cellular targets for
      anti-HIV therapeutic strategies. 

PMID- 24082144
TI  - Molecular crowding limits translation and cell growth.
AB  - Bacterial growth is crucially dependent on protein synthesis and thus on the
      cellular abundance of ribosomes and related proteins. Here, we show that the slow
      diffusion of the bulky tRNA complexes in the crowded cytoplasm imposes a physical
      limit on the speed of translation, which ultimately limits the rate of cell
      growth. To study the required allocation of ancillary translational proteins to
      alleviate the effect of molecular crowding, we develop a model for cell growth
      based on a coarse-grained partitioning of the proteome. We find that coregulation
      of ribosome- and tRNA-affiliated proteins is consistent with measured growth-rate
      dependencies and results in near-optimal allocation over a broad range of growth
      rates. The analysis further resolves a long-standing controversy in bacterial
      growth physiology concerning the growth-rate dependence of translation speed and
      serves as a caution against premature identification of phenomenological
      parameters with mechanistic processes. 

PMID- 24082143
TI  - Taf7l cooperates with Trf2 to regulate spermiogenesis.
AB  - TATA-binding protein (TBP)-associated factor 7l (Taf7l; a paralogue of Taf7) and
      TBP-related factor 2 (Trf2) are components of the core promoter complex required
      for gene/tissue-specific transcription of protein-coding genes by RNA polymerase
      II. Previous studies reported that Taf7l knockout (KO) mice exhibit structurally
      abnormal sperm, reduced sperm count, weakened motility, and compromised
      fertility. Here we find that continued backcrossing of Taf7l(-/Y) mice from N5 to
      N9 produced KO males that are essentially sterile. Genome-wide expression
      profiling by mRNA-sequencing analysis of wild-type (WT) and Taf7l(-/Y) (KO)
      testes revealed that Taf7l ablation impairs the expression of many postmeiotic
      spermatogenic-specific as well as metabolic genes. Importantly, histological
      analysis of testes revealed that Taf7l(-/Y) mice develop postmeiotic arrest at
      the first stage of spermiogenesis, phenotypically similar to Trf2(-/-) mice, but
      distinct from Taf4b(-/-) mice. Indeed, we find that Taf7l and Trf2 coregulate
      postmeiotic genes, but none of Taf4b-regulated germ stem cell genes in testes.
      Genome-wide ChIP-sequencing studies indicate that TAF7L binds to promoters of
      activated postmeiotic genes in testis. Moreover, biochemical studies show that
      TAF7L associates with TRF2 both in vitro and in testis, suggesting that TAF7L
      likely cooperates directly with TRF2 at promoters of a subset of postmeiotic
      genes to regulate spermiogenesis. Our findings thus provide a previously
      undescribed mechanism for cell-type-specific transcriptional control involving an
      interaction between a "nonprototypic" core promoter recognition factor (Trf2) and
      an orphan TAF subunit (Taf7l) in mammalian testis-specific gene transcription. 

PMID- 24082145
TI  - Deficits in dopaminergic transmission precede neuron loss and dysfunction in a
      new Parkinson model.
AB  - The pathological end-state of Parkinson disease is well described from postmortem
      tissue, but there remains a pressing need to define early functional changes to
      susceptible neurons and circuits. In particular, mechanisms underlying the
      vulnerability of the dopamine neurons of the substantia nigra pars compacta (SNc)
      and the importance of protein aggregation in driving the disease process remain
      to be determined. To better understand the sequence of events occurring in
      familial and sporadic Parkinson disease, we generated bacterial artificial
      chromosome transgenic mice (SNCA-OVX) that express wild-type alpha-synuclein from
      the complete human SNCA locus at disease-relevant levels and display a transgene
      expression profile that recapitulates that of endogenous alpha-synuclein. SNCA
      OVX mice display age-dependent loss of nigrostriatal dopamine neurons and motor
      impairments characteristic of Parkinson disease. This phenotype is preceded by
      early deficits in dopamine release from terminals in the dorsal, but not ventral,
      striatum. Such neurotransmission deficits are not seen at either noradrenergic or
      serotoninergic terminals. Dopamine release deficits are associated with an
      altered distribution of vesicles in dopaminergic axons in the dorsal striatum.
      Aged SNCA-OVX mice exhibit reduced firing of SNc dopamine neurons in vivo
      measured by juxtacellular recording of neurochemically identified neurons. These
      progressive changes in vulnerable SNc neurons were observed independently of
      overt protein aggregation, suggesting neurophysiological changes precede, and are
      not driven by, aggregate formation. This longitudinal phenotyping strategy in
      SNCA-OVX mice thus provides insights into the region-specific neuronal
      disturbances preceding and accompanying Parkinson disease. 

PMID- 24082146
TI  - Synergistic inhibition of natural killer cells by the nonsignaling molecule CD94.
AB  - Peptide selectivity is a feature of inhibitory receptors for MHC class I
      expressed by natural killer (NK) cells. CD94-NKG2A operates in tandem with the
      polymorphic killer cell Ig-like receptors (KIR) and Ly49 systems to inhibit NK
      cells. However, the benefits of having two distinct inhibitory receptor-ligand
      systems are not clear. We show that noninhibitory peptides presented by HLA-E can
      augment the inhibition of NKG2A(+) NK cells mediated by MHC class I signal
      peptides through the engagement of CD94 without a signaling partner. Thus, CD94
      is a peptide-selective NK cell receptor, and NK cells can be regulated by
      nonsignaling interactions. We also show that KIR(+) and NKG2A(+) NK cells respond
      with differing stoichiometries to MHC class I down-regulation. MHC-I-bound
      peptide functions as a molecular rheostat controlling NK cell function. Selected
      peptides which in isolation do not inhibit NK cells can have different effects on
      KIR and NKG2A receptors. Thus, these two inhibitory systems may complement each
      other by having distinct responses to bound peptide and surface levels of MHC
      class I. 

PMID- 24082148
TI  - Significance of endangered and threatened plant natural products in the control
      of human disease.
AB  - One in five of the world's plant species is threatened with extinction according
      to the 2010 first global analysis of extinction risk. Tilman et al. predicted a
      massive ecological change to terrestrial plants within the next 50-100 y,
      accompanied by an increase in the number of global plant species facing
      extinction [Tilman D, et al. (2001) Proc Natl Acad Sci USA 98(10):5433-5440].
      Most of the drug-producing plant families contain endangered species never
      previously studied for their utility to human health, which strongly validates
      the need to prioritize protection and assessment of these fragile and endangered
      groups [Zhu F, et al. (2011) Proc Natl Acad Sci USA 108(31):12943-12948]. With
      little prior attention given to endangered and rare plant species, this report
      provides strong justification for conservation of the rare plant Diplostephium
      rhododendroides Hieron., as well as other potential drug-producing endangered
      species in this and other groups. 

PMID- 24082147
TI  - STAT3 activation in response to IL-6 is prolonged by the binding of IL-6 receptor
      to EGF receptor.
AB  - The activation of STAT3 by tyrosine phosphorylation, essential for normal
      development and for a normal inflammatory response to invading pathogens, is kept
      in check by negative regulators. Abnormal constitutive activation of STAT3, which
      contributes to the pathology of cancer and to chronic inflammatory diseases such
      as rheumatoid arthritis, occurs when negative regulation is not fully effective.
      SOCS3, the major negative regulator of STAT3, is induced by tyrosine
      phosphorylated STAT3 and terminates STAT3 phosphorylation about 2 h after initial
      exposure of cells to members of the IL-6 family of cytokines by binding
      cooperatively to the common receptor subunit gp130 and JAKs 1 and 2. We show here
      that when the epidermal growth factor receptor (EGFR) is present and active,
      STAT3 is rephosphorylated about 4 h after exposure of cells to IL-6 or oncostatin
      M and remains active for many hours. Newly synthesized IL-6 drives association of
      the IL-6 receptor and gp130 with EGFR, leading to EGFR-dependent
      rephosphorylation of STAT3, which is not inhibited by the continued presence of
      SOCS3. This second wave of STAT3 activation supports sustained expression of a
      subset of IL-6-induced proteins, several of which play important roles in
      inflammation and cancer, in which both IL-6 secretion and EGFR levels are often
      elevated. 

PMID- 24082149
TI  - Inequalities in avoidable hospitalisation by area income and the role of
      individual characteristics: a population-based register study in Stockholm
      County, Sweden.
AB  - BACKGROUND: Avoidable hospitalisations are hospital admissions for medical
      conditions that could potentially have been prevented by outpatient healthcare.
      They are used as an indicator of access to and quality of primary healthcare.
      AIM: To investigate the association between median area income and avoidable
      hospitalisation and whether potential differences can be explained by contextual
      or compositional factors. METHOD: Median area income was calculated for all 43
      city districts and municipalities in Stockholm County during 2005-2007 and
      grouped into quintiles. The association between median area income and avoidable
      hospitalisation was studied by calculating age-adjusted rates. To disentangle
      contextual and compositional effects, ORs with 95% CIs were calculated,
      controlling for individual age, sex, country of birth, marital status and
      socioeconomic position. RESULTS: Rates of avoidable hospitalisation were higher
      in areas with lower income, 1535 per 100 000 inhabitants in the lowest area
      income quintile compared with 1179 in the highest area income quintile after age
      standardisation. For the age group 18-64 years, comparing the lowest quintile
      with the highest quintile, adjustment for individual characteristics of residents
      (compositional factors) reduced the crude OR from 1.52 (95% CI 1.44 to 1.60) to
      1.12 (95% CI 1.06 to 1.19). For the age group 65-79 years, the ORs were 1.28
      (1.21 to 1.36) and 1.06 (1.00 to 1.13), respectively. For those aged 80+ years,
      no association was found with area median income. CONCLUSIONS: Higher rates of
      avoidable hospitalisation in low-income areas indicate greater healthcare needs
      of people living there. This should be addressed by investing in outpatient care
      for lower socioeconomic groups. The composition of individuals must be considered
      when studying area characteristics and avoidable hospitalisation.

PMID- 24082150
TI  - More dialogue, more learning, more action.

PMID- 24082152
TI  - Compassionate communities: end-of-life care as everyone's responsibility.
AB  - In early 2013, an online survey of over 200 UK palliative care services published
      in the British Medical Journal found that most of these services were
      prioritizing 'community engagement' initiatives, most commonly adopting a
      'compassionate community' model. Later this same year, a report released by the
      National Council for Palliative Care and the charity Murray Hall Community Trust,
      described the increasing uptake of compassionate communities by palliative care
      services in England. This review examines this new policy and practice
      development in British end-of-life care explaining its conceptual origins and
      describing its policy importance to current practice. Why services are
      increasingly turning to community partnerships and the reasons they believe that
      this approach might enhance the effectiveness and reach of their clinical work
      are described. 

PMID- 24082151
TI  - Anaphylaxis: incidence, presentation, causes and outcome in patients in a
      tertiary-care hospital in Karachi, Pakistan.
AB  - BACKGROUND: Anaphylaxis is a potentially fatal condition requiring immediate
      resuscitation. Data regarding the epidemiology of anaphylaxis are limited and
      inconsistent. A reason for the variability was unavailability of a universally
      acceptable case definition till 2005. We reviewed cases using this new definition
      AIM: To review the incidence, clinical presentation, cause and outcome of
      anaphylaxis at a tertiary-care centre in a low-income country. DESIGN:
      Retrospective, case series METHODS: Chart review of all patients discharged from
      Aga Khan University Hospital between January 1988 and December 2012 (24 years)
      with anaphylaxis definition as per second National Institute of Allergy and
      Infection disease/Food Allergy and Anaphylaxis Network Symposium RESULTS: Total
      of 129 cases were found with mean age of 41.6 years (SD 18.8). Majority of
      patients had cutaneous features (76.7%), followed by respiratory (68.9%), cardiac
      (64.3%) and gastrointestinal (20.9%) symptoms, respectively. About 22.4% of
      patients had positive history for allergens out of which 31% (n = 9) were exposed
      to the same allergens. The common causes identified for anaphylaxis were drugs
      (60.5%), food (16.3%) and intravenous contrast (10.9%), respectively. Only 22.5%
      of cases received epinephrine as a part of their initial management. In four
      patients (3.1%) the cause of death was attributed to anaphylaxis. CONCLUSION:
      Anaphylaxis is a rare but life-threatening condition. Though cutaneous features
      are most common, their absence does not exclude the diagnosis. Drugs were the
      most common cause and epinephrine was not commonly used as first-line agent for
      its management.

PMID- 24082153
TI  - Long-term outcome of an AMAU--a decade's experience.
AB  - BACKGROUND: There is interest in emergency medical admissions, the outcomes of
      major reconfigurations and the development of systems and processes for Acute
      Medicine. We report on the long-term outcomes of an Acute Medical Admissions
      Unit, using a database of emergency admissions to St James' Hospital, Dublin,
      from 2002 to 2012. METHODS: All emergency admissions (67,971 episodes in 37,828
      patients) were tracked and in-hospital mortality, length of stay and emergency
      'wait' numbers and times summarized. We examined outcomes using generalized
      estimating equations, an extension of generalized linear models that permitted
      adjustment for correlated observations (readmissions). Margins statistics used
      adjusted predictions to test for interactions of key predictors while controlling
      for other variables using computations of the average marginal effect. RESULTS:
      By episode, the in-hospital mortality averaged 5.8% (95% CI 5.6-5.9%); the
      relative risk reduction (RRR) was 35.0% between 2002 and 2012, from 7.0% to 4.6%
      (P = 0.001), with a number needed to treat (NNT) of 40.7. By unique patient the
      in-hospital mortality averaged 10.3% (95% CI 10.0-10.6%) with a RRR of 60.0% from
      14.5% to 5.7% (P = 0.001), with an NNT of 11.4. Emergency Department 'wait'
      numbers decreased by 43%. The main mortality outcome predictors were Illness
      Severity, Charlson Comorbidity, Manchester Triage Category, O2 saturation, blood
      culture results, transfusion requirement and a primary respiratory or
      neurological diagnosis; the model had a high AUROC of 0.88 (95% CI 0.87, 0.88).
      CONCLUSION: Institution reform can result in substantial outcome and process
      measure benefits, improving care delivery to emergency medical admissions.

PMID- 24082154
TI  - Asbestos-related pleural plaques.

PMID- 24082156
TI  - The joy of caring.

PMID- 24082155
TI  - High intensity, interval exercise improves quality of life of patients with
      chronic heart failure: a randomized controlled trial.
AB  - BACKGROUND: The aim of this study was to evaluate the effect of high intensity,
      interval exercise on quality of life (QoL) and depression status, in chronic
      heart failure (CHF) patients. METHODS: A randomized controlled trial (phase III).
      Of the 100 consecutive CHF patients (NYHA classes II-IV, ejection fraction <=
      50%) that were randomly allocated to exercise intervention (n = 50, high
      intensity intermittent endurance training 30 s at 100% of max workload, 30 s at
      rest, for 45 min/day-by-12 weeks) or no exercise advice (n = 50), 72 (exercise
      group, n = 33, 63 +/- 9 years, 88% men, 70% ischemic CHF and control group, n =
      39, 56 +/- 11 years, 82% men, 70% ischemic CHF) completed the study. QoL was
      assessed using the validated and translated Minnesota Living with Heart Failure
      questionnaire. Depressive symptomatology was evaluated using the validated and
      translated Zung Depression Rating Scale (ZDRS). Maximal oxygen uptake (VO(2max))
      and carbon dioxide production (VCO(2max)) were also measured breath-by-breath.
      RESULTS: Data analysis demonstrated that in the intervention group MLHFQ score
      was reduced by 66% (P = 0.003); 6-min-walk distance increased by 13% (P < 0.05),
      VO(2max) level increased by 31% (P = 0.001), VCO(2max) level increased by 28% (P
      = 0.001) and peak power output increased by 25% (P = 0.001), as compared with the
      control group. CONCLUSION: High intensity, systematic aerobic training, could be
      strongly encouraged in CHF patients, since it improves QoL, by favorably
      modifying their fitness level.

PMID- 24082157
TI  - Food animal practice.

PMID- 24082158
TI  - An ethicist's commentary on the case of the declining farm dog.

PMID- 24082159
TI  - The wellness bucket.

PMID- 24082160
TI  - Evaluation of enzyme-linked immunosorbent assays performed on milk and serum
      samples for detection of neosporosis and leukosis in lactating dairy cows.
AB  - Serum and milk samples from 1229 cows on 22 Ontario dairy farms were individually
      tested for antibodies specific for bovine leukosis virus (BLV) and Neospora
      caninum by enzyme-linked immunosorbent assay (ELISA). Antibodies against BLV were
      present in 361 serum samples (29.4%) and 369 milk samples (30.0%). Comparing the
      2 tests, agreement was almost perfect (k = 0.86; 95% CI = 0.83 to 0.90) and the
      proportions of samples positive were not significantly different (P = 0.56). Both
      tests identified the same 3 herds free of bovine leukosis virus. Antibodies
      against N. caninum were detected in 138 serum samples (11.2%), and 111 milk
      samples (9.0%). Agreement between the 2 tests was moderate (k = 0.52; 95% CI =
      0.43 to 0.59). Four herds were free of neosporosis by the serum test, while 10
      herds were negative by the milk test. The ELISA on milk samples facilitates
      sample collection to classify herds free of BLV; the milk N. caninum ELISA was
      less reliable in predicting herd-level infection. 

PMID- 24082161
TI  - In-vitro comparison of 3 knotting techniques for lateral fabellotibial suture
      stabilization.
AB  - This study evaluated the biomechanical characteristics of a single self-locking
      knot (sSLK) and a double self-locking knot (dSLK) compared with the square knot
      (SQ) for stabilization of cranial cruciate ligament rupture. Each knot underwent
      monotonic tensile and cyclical loading. Starting tension, elongation, stiffness,
      and load to failure were all evaluated. A value of P < 0.05 was considered
      significant. Starting tension, overall stiffness, and load to failure were all
      significantly greater in both the sSLK and dSLK compared with the SQ. There was
      no difference in elongation among the knots. There were no significant
      differences in starting tension, elongation, stiffness, and load to failure
      between the sSLK and the dSLK. The self-locking knots were stronger and stiffer
      than the SQ; there is no biomechanical advantage in using the dSLK compared with
      the sSLK. 

PMID- 24082162
TI  - A retrospective investigation of feline gastrointestinal parasites in western
      Canada.
AB  - Between 1998 and 2008, feline fecal specimens were submitted to provincial
      veterinary diagnostic laboratories in Regina and Saskatoon, Saskatchewan, for
      sucrose centrifugation-flotation (n = 635), parasite identification (n = 17),
      and/or Giardia (n = 283) or Cryptosporidium (n = 266) commercial direct
      immunofluorescence assay (IFA). The most commonly detected parasites on flotation
      were Toxocara cati (4.7%), Isospora (3.8%), and taeniid eggs (Echinococcus or
      Taenia) (1.3%). Cats less than 2 years of age were twice as likely to have a
      positive parasite test as cats older than 2 years. Using IFA, Giardia was
      detected in 9.9% of samples, and Cryptosporidium in 2.3% of samples. Relative to
      IFA, flotation had sensitivity values of 39% and 50% for detection of Giardia and
      Cryptosporidium, respectively. Giardia and Isospora were detected in a higher
      proportion of samples in our study population than reported in the general cat
      population in western Canada. This study highlights the importance of sensitivity
      when interpreting diagnostic tests and provides information to guide region
      specific recommendations for helminth parasite prevention and treatment. 

PMID- 24082163
TI  - The influence of perfusate volume on antimicrobial concentration in synovial
      fluid following intravenous regional limb perfusion in the standing horse.
AB  - This study investigated the influence of perfusate volume on antimicrobial
      concentration in synovial fluid following intravenous regional limb perfusion
      (IVRLP) and assessed the efficacy of low volume IVRLP. The front limbs of 9
      horses were randomly assigned to 1 of 3 volume groups: 10 mL (Group 1), 30 mL
      (Group 2), or 60 mL (Group 3). A tourniquet was applied distal to the carpus and
      the limbs were perfused with 500 mg genta-micin diluted to the assigned volume
      via a catheter placed in the lateral palmar digital vein at the level of the
      proximal sesamoid bones. Synovial fluid samples were collected from the
      metacarpophalangeal joint at 30 minutes, followed by removal of the tourniquet.
      Gentamicin concentration in synovial fluid was detected using a fluorescence
      polarization immunoassay. There were no statistically significant differences
      among gentamicin concentrations in synovial fluid among perfusate volume groups.
      Mean gentamicin concentration in Group 1 (125.9 MUg/mL) was higher than Group 2
      (82.7 MUg/mL) and Group 3 (56.1 MUg/mL). 

PMID- 24082164
TI  - Suspected hypothyroid-associated neuropathy in a female rottweiler dog.
AB  - A 7-year-old, 46-kg spayed female rottweiler dog was presented with sudden onset
      of disorientation, bilateral convergent strabismus, and enophthalmos. Diagnostic
      workup revealed hypothyroid-associated cranial neuropathy. Symptoms abated
      considerably upon treatment with levothyroxine-sodium (T4) at an initial dose of
      800 MUg/kg body weight (BW), PO, q12h, which was reduced 3 days later to 600
      MUg/kg BW, q12h due to severe agitation and panting. Two weeks later the dosage
      of the levothyroxine-sodium (T4) was reduced to 400 MUg/kg BW in the morning and
      600 MUg/kg BW in the evening. Eight weeks after the initial presentation, the dog
      had recovered with only mild convergent strabismus in the right eye. This is the
      first case report of suspected hypothyroid-associated neuropathy resulting in
      these symptoms. 

PMID- 24082165
TI  - Application of a new diagnostic approach to a bovine genital campylobacteriosis
      outbreak in a Saskatchewan beef herd.
AB  - A new real-time quantitative polymerase chain reaction (qPCR) test was used to
      diagnose Campylobacter fetus subsp. venerealis infection associated with dramatic
      reproductive losses in a commercial cow-calf herd. The results were verified with
      repeated culture, phenotypic characterization of the organism and DNA sequencing.
      This case demonstrates the need for a practical field test for C. fetus subsp.
      venerealis and the importance of considering this organism as a potential cause
      of pregnancy failure in beef herds. 

PMID- 24082166
TI  - Subcutaneous hemangiosarcoma induced by a foreign body (steel staple) in a cat.
AB  - An 8-year-old, female domestic shorthair cat was presented with a ventral
      abdominal subcutaneous mass. A radiograph showed that the center of the mass
      contained what appeared to be steel sutures, presumed to be from an
      ovariohysterectomy performed 7 years earlier. The excised mass was irregular and
      contained numerous pockets filled with friable necrotic material and hemorrhages
      that were dissected by fibrous connective tissue bands. Multiple tangled and
      fragmented pieces of steel staples were deeply embedded within the mass.
      Histologically, the mass was non-encapsulated, densely cellular, and
      infiltrative. Neoplastic cells lined caverns and channels and were factor VIII
      positive by immunohistochemistry. The neoplastic cells were oval to round with
      granular cytoplasm and vesicular nucleus and exhibited moderate cellular and
      nuclear pleomorphism. A diagnosis of subcutaneous hemangiosarcoma was made. To
      our knowledge, this is the first report of foreign body associated
      hemangiosarcoma and the first case of steel staple associated neoplasm in
      domestic animals. 

PMID- 24082167
TI  - Presumptive acute lung injury following multiple surgeries in a cat.
AB  - A 12-year-old, 3.5-kg spayed female domestic shorthair cat had a tracheal mass
      identified as malignant B-cell lymphoma. The cat had tracheal resection and
      subsequently developed laryngeal paralysis. Due to multiple episodes of
      respiratory distress the cat subsequently had tracheal surgeries. Finally, the
      cat had a sudden onset of severe respiratory distress and collapsed. Computed
      tomography imaging and arterial blood gas analysis supported a diagnosis of acute
      lung injury. 

PMID- 24082168
TI  - Metastatic malignant pilomatrixoma, acanthomatous ameloblastoma, and liver tumor
      in a dog with polyphagia, polyuria, polydipsia, and weight loss.
AB  - A 12-year-old, spayed female, Labrador dog was presented for evaluation of
      polyphagia, polyuria, polydipsia, weight loss of 2 months duration, and multiple
      cutaneous and subcutaneous masses. The dog was diagnosed with malignant
      pilomatrixoma with renal, lung, and lumbar metastases. This report describes an
      atypical presentation of malignant pilomatrixoma. 

PMID- 24082169
TI  - Protein-losing nephropathy associated with Borrelia burgdorferi seropositivity in
      a soft-coated wheaten terrier: response to therapy.
AB  - A soft-coated wheaten terrier was examined for lameness with subsequent
      identification of protein-losing nephropathy, hypoalbuminemia, hyperglobulinemia,
      and seroconversion to Borrelia burgdorferi. Following doxycycline therapy, the
      urine protein loss decreased significantly and serum albumin concentration
      remained close to or within the reference interval for over 3 years, contrary to
      the reported poor prognosis for renal disease associated with B. burgdorferi or
      protein-losing nephropathy of soft-coated wheaten terriers. 

PMID- 24082170
TI  - Bacterial sepsis resulting in severe systemic illness and euthanasia in a dog
      with cutaneous angiomatosis.
AB  - A Labrador retriever dog was euthanized after unsuccessful treatment for severe,
      progressive, lethargy, gastroenteritis, icterus, and swelling of a previously
      diagnosed cutaneous angiomatosis lesion. The body was submitted for necropsy.
      This is the first report that suggests that cutaneous angiomatosis lesions may
      have caused life-threatening systemic complications in a dog. 

PMID- 24082171
TI  - The animal health and welfare consequences of foie gras production.

PMID- 24082172
TI  - Vulnerable communication.

PMID- 24082173
TI  - The rate and pattern of bcl-2 and cytokeratin 15 expression in trichoepithelioma
      and nodular Basal cell carcinoma: a comparative study.
AB  - CONTEXT: Histopathological evaluations can differentiate between clinically
      resembling trichoepithelioma (TE) and basal cell carcinoma (BCC) unless the
      biopsy specimens are small or superficial. Previous studies used
      immunohistochemical evaluation for Bcl-2 and cytokeratin 15 (CK15), in attempts
      to differentiate between these two entities, with heterogeneous findings. AIMS:
      This study intended to compare the rate and patterns of Bcl-2 and CK15
      expressions between specimens of TE and nodular BCC. SETTINGS AND DESIGN: Case
      series including formalin-fixed, paraffin-embedded cutaneous biopsies. SUBJECTS
      AND METHODS: Twenty-two BCC and 12 TE specimens were stained for Bcl-2 and CK15
      and examined microscopically. The rate and patterns of expressions were compared
      between the two groups. STATISTICAL ANALYSIS USED: Statistical analysis was
      performed using the statistical software (SPSS version 16.0; SPSS Inc., Chicago,
      IL, USA), Pearson Chi-square, or Fisher's exact tests, wherever appropriate.
      RESULTS: The two groups were comparable for the expression rate and patterns of
      Bcl-2 (86.4%: 5 central, 14 diffuse in BCC vs. 83.3%: 2 central, 8 diffuse in TE;
      P = 0.59 and 0.54 for rate and pattern, respectively). The rate of CK15
      expression was significantly higher in TE specimens (66.7%: 4 central, 3 diffuse,
      1 peripheral vs. 4.5%: 1 central; P < 0.001). The positive likelihood ratio in
      distinguishing the two neoplasms was 14.7 (95% confidence interval: 2.1-103.7).
      CONCLUSIONS: CK15 but not Bcl-2 staining may help in differentiating between BCC
      and TE even in BCCs with follicular differentiation.

PMID- 24082174
TI  - Epidemiological study of insect bite reactions from central India.
AB  - INTRODUCTION: The physical effects of the arthropod bites on human skin receive
      less attention, especially in the rural areas where the per capita income is
      less. Ours is a rural-based hospital, the vicinity having more of plants, trees,
      and forests; we undertook the study to find out the relation of insect bite
      dermatitis in a rural area. MATERIALS AND METHODS: The study was carried out in
      the Dermatology outpatient department of our institute on 100 subjects of insect
      bite dermatitis who were questioned retrospectively about the sequence of events
      besides their environmental and living conditions. They were examined thoroughly
      and the relevant clinical findings were noted, also taking into account the prior
      treatment taken by them, if any. RESULTS AND CONCLUSIONS: It was found that
      insect bite dermatitis has no age or gender preponderance, and the protective
      factors for the same are use of full sleeve clothes and keeping the doors and
      windows closed at night. On the contrary, the risk factors are residence in areas
      of heavy insect infestation, use of perfumes and colognes, warm weather in spring
      and summer and the lack of protective measures. However, there was no direct
      association of atopy with increased risk of developing insect bite dermatitis.

PMID- 24082175
TI  - Prescribing practices of topical corticosteroids in the outpatient dermatology
      department of a rural tertiary care teaching hospital.
AB  - BACKGROUND: Inappropriate or excessive use of topical corticosteroids can lead to
      cutaneous and systemic adverse effects which occur more commonly with the use of
      very potent steroids. Monitoring and analysis of the prescription practices of
      topical steroids can help to achieve rational prescription of these drugs. AIM:
      The present study was carried out to study and analyze the pattern of prescribing
      topical corticosteroids among outpatients attending the dermatology clinic in a
      rural tertiary care and teaching hospital, Ambajogai, Maharashtra. MATERIALS AND
      METHODS: A cross-sectional descriptive study was conducted for a duration of two
      months from August 2011 to September 2011, and 500 prescriptions were randomly
      collected from the dermatology pharmacy and analyzed. RESULTS: About 66% of the
      prescriptions contained four to five drugs per prescription. Topical steroids
      were given in 28.4% of all the prescriptions. In almost all the prescriptions,
      strength, quantity of the steroid to be used, frequency, site, and duration of
      application was not mentioned. The chief complaints and diagnoses were not
      mentioned in about 85% of the prescriptions for topical corticosteroids. About
      94.36% of the prescriptions contained very potent steroids. CONCLUSION:
      Inadequate prescribing information is a clear characteristic of the
      dermatological prescriptions containing topical corticosteroids. Doctors should
      be educated about the importance of giving patients sufficient information
      regarding the use of steroids. There is a need to revise hospital formulary where
      low-potency steroids can also be included along with potent ones so that the
      latter can be avoided in conditions where they are unnecessary.

PMID- 24082177
TI  - Triads in dermatology.
AB  - It is imperative for any dermatology resident to have a good knowledge of the
      various triads in dermatology. For an easy grasp over this topic, we have grouped
      the various triads on the basis of their etiologies. 

PMID- 24082178
TI  - Rebamipide: A Novel Agent in the Treatment of Recurrent Aphthous Ulcer and
      Behcet's Syndrome.
AB  - Rebamipide is an amino acid analog of 2 (1H)-quinolinone. It is being introduced
      and used since 1980 for the treatment of peptic ulcer. Its therapeutic use in
      recurrent aphthous ulcer was not known. It acts by the decrease in oxygen
      radicals, increase in blood flow and production of protective prostaglandins in
      ulcer mucosa, which accelerates the process of healing. In this article, we focus
      on the pharmacodynamics, pharmacokinetics, side-effects and other therapeutic
      uses of Rebamipide. It will be a new and effective drug in the dermatologists'
      drug armamentarium for the treatment of aphthous ulcers and related diseases. 

PMID- 24082179
TI  - Oral ketotifen and topical antibiotic therapy in the management of pruritus in
      prurigo nodularis: a randomized, controlled, single-blind, parallel study.
AB  - AIMS: To evaluate the role of oral ketotifen and topical antibiotic therapy in
      the management of pruritus in prurigo nodularis (PN) patients. MATERIALS AND
      METHODS: Twenty-seven patients with PN and a history of atopy with raised IgE
      were included in this study in a dermatology clinic. All patients had positive
      growth of Staphylococcus aureus on the lesional skin swab. All patients received
      topical halobetasol and oral hydroxyzine for 4 weeks. In addition, all patients
      in the study group received oral ketotifen and topical antibiotic therapy for 4
      weeks. Randomization was performed by using a table of random numbers, and the
      participants were randomly allocated to one of the two groups in the study. The
      study was a single-blind study, and the blinding was done by the investigator.
      RESULTS: Of the 14 patients in the study group, 9 had complete relief from
      pruritus by the end of first week, which was maintained till the end of 4 weeks.
      In the control group, mild to moderate reduction in the intensity of pruritus in
      the PN lesions of all patients were noted by the end of the first week. No
      further improvement in the level of pruritus was noted in the participants during
      the trial period. The treatment was well tolerated by the patients, and the
      adverse reactions of drugs were minimal in both groups. CONCLUSIONS: This study
      showed that oral ketotifen and topical antibiotic therapy can be helpful in the
      management of pruritus in PN patients.

PMID- 24082180
TI  - Immunotherapy with intralesional Candida albicans antigen in resistant or
      recurrent warts: a study.
AB  - BACKGROUND: Warts are sometimes resistant or they tend to recur after every
      possible destructive therapy. Immunotherapy with skin-test antigens has been used
      as a viable therapeutic option in such recalcitrant cases. AIM: The aim of the
      study was to evaluate the response of resistant or recurrent warts to
      intralesional Candida albicans antigen immunotherapy. MATERIALS AND METHODS: A
      total of 40 patients with resistant or recurrent warts who showed a positive test
      reaction to C. albicans antigen were given intralesional injections of purified
      C. albicans antigen solution in a single wart at 3-weekly intervals for a total
      of three doses. The patients were monitored for resolution of the injected wart
      as well as other untreated warts. The patients who responded positively were then
      followed up for any relapses over the next 6 months. Adverse events, if any, were
      also documented. RESULTS: Of the 40 patients enrolled in the study, 34 completed
      the total treatment protocol of three injections and 6 months of follow-up. In
      these 34 patients, 19 (56%) showed a complete resolution of warts at all places
      on the body. In addition, two patients (6%) showed a partial or complete
      resolution of the treated wart, but there was no effect on the untreated warts.
      Thirteenpatients (38%) failed to show any response to the treatment regimen. In
      all patients showing resolution of all the warts, there were no relapses at any
      site over the next 6 months of follow-up. The most common adverse effect seen was
      pain during the intralesional injection. CONCLUSIONS: Intralesional Candida
      immunotherapy seems to be an effective treatment option in more than half of the
      patients who fail to show a positive response to destructive modes of treatment
      or in whom there are multiple recurrences. LIMITATIONS: The small sample size and
      lack of control group are the main limitations of the study.

PMID- 24082181
TI  - Primary cutaneous diffuse large B-cell lymphoma of the upper limb: a fascinating
      entity.
AB  - Primary cutaneous lymphomas are defined as lymphoid neoplasms that present
      themselves clinically on the skin and do not have extra-cutaneous disease, when
      the diagnosis is made or even after 6 months of the diagnosis. Primary cutaneous
      lymphomas of B-cells are less frequent than lymphomas of T-cells. Primary B-cell
      lymphomas have a better prognosis than secondary B-cell lymphomas. Primary B-cell
      cutaneous lymphomas are classified into five types according to the World Health
      Organization and European Organization for Research and Treatment of Cancer
      classification. The primary diffuse large B-cell cutaneous lymphoma - leg type
      corresponds to approximately 5-10% of the B-cell cutaneous lymphomas. It is
      predominantly seen in elderly people and has a female preponderance. Skin lesions
      can be single, multiple, and even grouped. A 5-year survival rate ranges from 36
      to 100% of the cases. The expression of Bcl-2, presence of multiple lesions, and
      involvement of both the upper limbs lead to a worse prognosis. Very few cases
      have been described in the literature. 

PMID- 24082182
TI  - "Pseudo" Nomenclature in Dermatology: What's in a Name?
AB  - In the bewildering array of scientific nomenclature in the medical field, it is
      important to use correct terminology, know their aberrations and the reason
      behind a specific terminology. This paper is an attempt towards compiling all the
      pseudo-nomenclatures coined in dermatology, in order to make it easier to retain
      and recollect these pseudo names, signs, morphology, diseases, and conditions. It
      is also imperative to know the true entities that these pseudo names masquerade
      as, so as to understand the explanation for assigning the term 'pseudo' to these
      conditions. A total of 52 pseudo-terms have been compiled here in reference to
      dermatology. Most of these pseudo-nomenclatures were coined due to some clinical
      or histopathological resemblance to the true conditions, while some were
      premature conclusions drawn from a flawed understanding of the basic nature of
      the condition. Clear understanding of each of these terms and the explanation
      behind them being pseudo will enable a dermatologist to avoid misdiagnosis and
      needless confusion. 

PMID- 24082183
TI  - Basal cell carcinoma, oculo-cutaneous albinism and actinic keratosis in a native
      Indian.
AB  - The report highlights the occurrence of basal cell carcinoma in a native Indian
      with oculo-cutaneous albinism, an association not frequently encountered. The
      clinical and histopathological features, which assisted to form the diagnosis,
      are outlined. A high degree of suspicion and timely recognition of the
      potentially aggressive neoplasm, under this unusual circumstance, is the key to
      its diagnosis. 

PMID- 24082184
TI  - Docetaxel-induced Hand and Foot Syndrome in a Patient with Metastatic Breast
      Carcinoma.
AB  - Hand and foot syndrome (HFS) is a well-known complication of chemotherapeutic
      drugs given in a dose-dense manner. Our patient was a 52-year-old female with
      metastatic breast carcinoma on salvage chemotherapy regimen with docetaxel at a
      dose of 60 mg/m(2). The patient had grade 3 HFS characterized by symmetrical,
      tender, and erythematous skin lesions over the palms and soles associated with
      dysesthesia necessitating interruption of treatment. She developed this syndrome
      at a much lower dose than previously described due to her altered hepatic
      function. An insight regarding this unique distressing side-effect and assessment
      of various contributing factors would help us identify and treat the patient at
      the earliest. 

PMID- 24082185
TI  - Hallermann-streiff syndrome.
AB  - Hallermann-Streiff syndrome (HSS) is a rare disorder characterized by
      dyscephalia, with facial and dental abnormalities. We report a 12-year-old female
      child who presented with abnormal facial features, dental abnormalities and
      sparse scalp hair. 

PMID- 24082186
TI  - Ichthyosiform large plaque parapsoriasis: report of a rare entity.
AB  - Large plaque parapsoriasis (LPP) is an idiopathic, chronic scaly dermatosis
      classified within parapsoriasis group of diseases, occurring commonly in middle
      aged patients of all races and geographic regions. LPP and its variants are
      closely related to the patch stage of mycosis fungoides. The two types of LPP
      mostly described are the poikilodermatous and retiform parapsoriasis. We are
      reporting an ichthyosiform LPP for its rarity. 

PMID- 24082187
TI  - Generalized lichenoid drug eruption associated with imatinib mesylate therapy.
AB  - Imatinib mesylate (IM), an anticancer drug, has been widely used to treat chronic
      myeloid leukemia (CML), gastrointestinal stromal tumors (GIST), and dermato
      fibrosarcoma protuberans. Cutaneous reactions to IM have been reported to occur
      in varying number of patients in different case series. Non-lichenoid cutaneous
      reactions secondary to IM have been well-documented in the literature and are the
      commonest non-hematologic adverse reactions associated with its use. Lichenoid
      drug eruption (LDE) associated with IM therapy has rarely been reported in the
      literature. A case of a generalized LDE associated with IM therapy has been
      described here for its rarity and interesting clinical presentation. As the
      clinical usage of IM is increasing, one might expect an increasing number of
      similar patients in the future. It is thus important to realize the potential of
      IM to produce LDE and to differentiate this entity from idiopathic lichen planus.
      In the present article, the reports of IM-associated LDE, described in the PubMed
      and Medline database (in English language literature), have also been reviewed. 

PMID- 24082188
TI  - Papular acantholytic dyskeratosis localized to the perineal and perianal area in
      a young male.
AB  - A case of Papular acantholytic dermatosis restricted to the perianal area is
      being reported in a 26 year old male without involvement of the genitalia, groin
      and upper thighs for the first time in English literature. The patient presented
      with long standing grayish white confluent papules with eroded areas in the
      perianal region which were asymptomatic for a long time before the area got
      macerated. He did not respond to many weeks of topical steroids but is now
      showing improvement with topical tacrolimus ointment 0.1% applied twice daily.
      This entity appears to be very uncommon and also underreported. It is also
      suggested that this entity be included in the long list of non venereal
      anogenital lesions as it may mimic perianal warts or molluscum contagiosum. 

PMID- 24082190
TI  - Epidermotropic metastatic melanoma with perilesional depigmentation in an Indian
      male.
AB  - Melanoma is a rare form of cutaneous malignancy encountered in the dark skin
      population. Epidermotropic metastatic melanoma is a rare form of cutaneous
      metastatic melanoma which can mimic primary melanoma on histopathology. Hence its
      differentiation is of immense prognostic importance. The occurrence of rim of
      depigmentation around the primary cutaneous melanoma has previously been reported
      to portend a bad prognosis. The occurrence of vitiligo like lesions in patients
      with metastatic melanoma in comparison has a better prognosis. However the
      occurrence of depigmentation around the secondaries is rare and its importance is
      not well known. Hence we wish to report a case of epidermotropic metastatic
      melanoma with perilesional depigmentation in a 78 year old Indian male. 

PMID- 24082191
TI  - Anti scl-70 antibody positive systemic sclerosis in a patient with lung cancer: a
      paraneoplastic or a purely coincidental phenomenon?

PMID- 24082192
TI  - Greyish verrucous plaque with erosions on the perianal area.

PMID- 24082193
TI  - Discordant HIV Couple: Analysis of the Possible Contributing Factors.
AB  - Several intricacies still abound with respect to HIV infection. Discordance is
      one such intriguing aspect of HIV infection. Out of 35 discordant couples
      included in the study. husbands were positive in 29 couples and wives in 6.
      Pre/extramarital affairs was the probable reason for HIV infection in 23 out of
      29 discordant males, and 2 out of 6 discordant females. Even though, decreased
      frequency of sexual acts between the couple was the reason for discordance in a
      few, but in majority of the couples who had regular sexual contact for many
      years, the exact cause for discordance could not be ascertained. inherent
      resistance to HIV in some individuals may be the reasons for the discordance. 

PMID- 24082194
TI  - A case of syringocystadenoma papilliferum on lower leg: a rare location.
AB  - An 18 years old male presented with a slowly increasing multiple papulonodular
      lesions on his left leg since birth. No definite diagnosis was made on clinical
      ground. But verrucous epidermal naevus with secondary change and appendageal
      tumor was suspected on clinical examination. Histopathological examination
      revealed syringocystadenoma papilliferm (SCAP). SCAP is very rare on lower leg.
      Only one case of SCAP on lower leg has been reported in literature so far, which
      was superimposed on an organoid nevus. The case is reported for unusual location
      and unusual presentation. 

PMID- 24082195
TI  - Hyperkeratotic Palmoplantar Lichen Planus in a child.
AB  - Lichen planus (LP) is a common idiopathic inflammatory disorder that affects the
      flexor aspect of the wrists, the legs, and the oral and genital mucosa. Depending
      upon the site of involvement, LP can be divided into mucosal, nail, scalp, or
      palmoplantar types. Palmoplantar LP can pose a diagnostic problem to the
      clinician as it resembles common dermatoses like psoriasis, verruca, corn,
      calluses, lichenoid drug eruption, and papular syphilide of secondary syphilis.
      In this case report, we describe a 4-year-old male child who presented with
      highly pruritic erythematous to violaceous hyperkeratotic papules and plaques on
      his palms and soles. Typical LP papules were noted on the upper back.
      Histopathology of the papular lesion showed features of LP. Dermatoscopy of a
      papule from the back showed the characteristic Wickham striae. We report this
      rare involvement of palm and soles in a case of childhood LP. 

PMID- 24082196
TI  - Pilomatrixoma - Presented as Hypopigmented Tender Nodule: Diagnosed by FNAC: A
      Case Report with Review of Literature.
AB  - Pilomatrixoma (PMX) is a skin appendage tumor of hair matrix origin, which
      usually occurs on the face or upper extremities. Although the lesion can appear
      at any age, it is commonly seen in children and is more common in females.
      Despite being better defined, pilomatricomas continue to be frequently
      misdiagnosed and are not usually considered in differential diagnoses, either in
      clinical set-up or during cytological reporting. They typically present as a
      superficial, firm, solitary, slow-growing, painless mass in the dermis. The
      overlying skin may be normal or exhibit a bluish-red discoloration or ulceration.
      We report an 18-year-old girl presented with tender, subcutaneous nodule with
      overlying skin showing atrophy and hypopigmentation. Clinically, it was diagnosed
      as neurofibroma and sent for FNAC. We offered precise diagnosis of pilomatrixoma
      on cytological examination, (where chances of wrong diagnosis are very high) and
      it was subsequently confirmed by histopathology. We discuss the varied clinical
      presentations, diagnostic difficulties, and differential diagnoses of PMX. 

PMID- 24082197
TI  - A Case of Adult-Onset Still's Disease Presenting with Urticated Plaques and Acute
      Myopericarditis.
AB  - Adult onset Still's disease (AOSD) is a systemic inflammatory disorder of unknown
      etiology characterized by spiking fever, evanescent skin rash, arthralgia or
      arthritis, involvement of various organs, and predominantly neutrophilic
      leucocytosis. AOSD, although uncommon, has a characteristic constellation of
      clinical and laboratory features and should be considered in the differential
      diagnosis of pyrexia of unknown origin associated with a rash and arthralgia. The
      diagnosis is one of clinical suspicion and it is essential that infections,
      malignancy, and other rheumatic diseases are excluded. We report a case which
      illustrates the typical features of AOSD that were treated with steroids and
      azathioprine. 

PMID- 24082198
TI  - Toxic epidermal necrolysis due to concomitant use of lamotrigine and valproic
      Acid.
AB  - Anti-epileptic drugs can be associated with a wide spectrum of cutaneous adverse
      reactions ranging from simple maculopapular rashes to more severe and life
      threatening reactions like Stevens-Johnson syndrome and toxic epidermal
      necrolysis. These rashes are well documented with older antiepileptic drugs like
      phenytoin, phenobarbitone and carbamazapine. Lamotrigine is a newer, unrelated
      antiepileptic drug that causes skin rashes in 3-10% of new users. Higher starting
      dose or rapid escalation, concurrent treatment with valproic acid, and a previous
      history of a rash with other antiepileptic drugs are well recognized risk factors
      for lamotrigine related serious rashes. We report two patients with toxic
      epidermal necrolysis, resulting from concomitant use of lamotrigine and valproic
      acid. It is emphasized that clinicians adhere to the recommended dosage
      guidelines and adopt a slow dose titration when initiating treatment with
      lamotrigine. 

PMID- 24082199
TI  - Botryomycosis.
AB  - Botryomycosis is a rare chronic bacterial granulomatous disease that usually
      involves skin and rarely viscera. Main etiological agent is Staphylococcus aureus
      and less commonly Pseudomonas spp., Escherichia coli, Proteus spp., Streptococcus
      spp. We here report a case of 32-year-old male with polymicrobial botryomycosis
      on forehead and on frontal scalp. Culture from lesions revealed growth of S.
      aureus initially. Partial resolution was achieved with cefadroxyl and clavulanic
      acid, rifampicin, and linezolid. Subsequent repeat culture revealed E. coli
      sensitive to netilmycin. Slow and steady resolution was achieved with surgical
      debridement and combination therapy of injectable netilmycin and oral
      sufomethoxazole and trimethoprim for a prolonged period. 

PMID- 24082200
TI  - Acrokeratosis verruciformis of hopf along lines of blaschko.
AB  - Acrokeratosis verruciformis of Hopf (AKV) is a rare genodermatosis presenting as
      multiple plane wart-like lesions symmetrically distributed on dorsum of hands and
      feet. Its pathogenesis is unknown. A case of 24 years old female is described
      with multiple hyperpigmented, hyperkeratotic papules on the left side of body
      since 5 years along the lines of Blaschko. Histopathology showed changes of AKV.
      Other unusual findings were the absence of family history, extensive lesions with
      flexural, and genital involvement. 

PMID- 24082201
TI  - Multiple sub-epidermal calcified nodule mimicking eruptive xanthoma: a case
      report and review of the literature.
AB  - Sub-epidermal calcified nodule (SCN) is an uncommon form of idiopathic
      calcinosis. It usually occurs in children, particularly in the head and neck
      region, presenting as a solitary, painless, yellow-white nodule with
      papillomatous features. These lesions occur twice as common in males compared
      with females. The pathogenesis is uncertain, but the clinical and histological
      features of this lesion are distinctive. We report a case of 22-year-old man with
      multiple nodules bilaterally located on the dorsum of hands simulating eruptive
      xanthoma. Histopathological examination of one of the excised lesion confirmed
      the diagnosis showing epidermal and sub-epidermal deposition of calcium. This
      paper presents a review of the literature and adds a new case of SCN. 

PMID- 24082202
TI  - Erythema nodosum as azathioprine hypersensitivity reaction in a patient with
      bullous pemphigoid.
AB  - A 65-year-old woman with bullous pemphigoid presented with fever and several red
      purple nodular subcutaneous lesions on both lower legs 1 week after starting
      treatment with azathioprine (AZA). Biopsy of a skin nodule was compatible with
      erythema nodosum (EN) and hypersensitivity reaction to AZA was suspected. AZA was
      subsequently discontinued, observing complete remission of fever and EN within 2
      weeks. This case highlights the importance of recognizing EN as a possible
      manifestation of hypersensitivity reaction to AZA. 

PMID- 24082203
TI  - Progressive systemic sclerosis in a child.
AB  - Systemic sclerosis is a clinically heterogeneous systemic disease affecting the
      connective tissues of skin, walls of blood vessels and internal organs like lung,
      heart and kidneys. Systemic sclerosis is very unusual in pediatric population.
      Children represent fewer than 10% of all cases. We report a case of 11 years old
      girl of progressive systemic sclerosis presenting with features of cutaneous
      sclerosis, microstomia, mask-like facies, sclerodactyly, esophageal dysmotility,
      Raynaud's phenomenon, arthralgia and pulmonary fibrosis. 

PMID- 24082204
TI  - Vitamin k deficiency bleeding presenting as nodular purpura in infancy: a rare
      and life-threatening entity.
AB  - Vitamin K deficiency bleeding (VKDB) disorder is an uncommon entity, which occurs
      due to inadequate activity of vitamin K-dependant coagulation factors. An 8
      months-old exclusively breast-fed male infant presented with multiple, purpuric
      and nodular non-collapsible swellings on trunk of 4 days duration. Investigations
      revealed raised activated partial thromboplastin time and prothrombintime.
      Fibrinogen level and platelet counts were normal. Late VKDB usually presents as
      intra-cranial or mucosal hemorrhages.([1]) Though skin and mucosal bleeding may
      occur in 1/3(rd) of infants with VKDB, 'nodular purpura' is not the common
      presenting feature. Earlier recognition of VKDB and immediate
      investigation/treatment helps prevent the potentially fatal outcome of the
      disease. Very little is mentioned about this entity in dermatology literature. 

PMID- 24082205
TI  - Abrikossoff's Tumor: An Unusual Presentation.
AB  - Abrikossoff's tumor or granular cell tumor is an infrequent benign neoplasm,
      first described by the Russian pathologist Abrikossoff in 1926. The neoplasm can
      affect all parts of the body with head and neck areas affected in 45-65% of
      patients. More than half of the head and neck lesions are localized to the oral
      cavity, especially the tongue. An aggressive malignant form of granular cell
      myoblastoma that metastasizes is rare. The treatment of choice of Abrikossoff's
      tumor is local surgical excision with a wide margin. Here, we present a case of
      Abrikossoff's tumor, occurring in the upper arm, presenting as a panniculitis
      like lesion. 

PMID- 24082206
TI  - A Case of Congenital Erythropoietic Porphyria without Hemolysis.
AB  - Porphyrias are group of disorders caused by deficiency of the enzymes in heme
      synthetic pathway. Congenital erythropoietic porphyria (CEP) is an extremely rare
      disease with mutation in the gene that codes for uroporphyrinogen III synthase
      leading to accumulation of porphyrin in different tissues and marked cutaneous
      photosensitivity. Here, we describe a case of CEP with infancy onset blistering,
      photosensitivity, red colored urine and teeth along with scarring but without any
      feature of hemolysis. 

PMID- 24082207
TI  - Oral hemorrhagic blister: an enigma.
AB  - Angina bullosa hemorrhagica (ABH) is a disorder of unclear aetiology
      characterized by abrupt and unprovoked presentation of blood-filled blister over
      the oral mucosa. Histopathology reveals sub epithelial blister containing
      erythrocytes with superficial perivascular lymphocytic infiltrate. We report two
      cases of ABH of which one was idiopathic and other was associated with chronic
      renal failure on hemodialysis. 

PMID- 24082208
TI  - Cutaneous schwannoma masquerading as trichilemmal cyst over scalp in a young
      male.
AB  - Schwannomas are benign tumors derived from Schwann cells. They are comparatively
      rare on scalp and easily mistaken for tumors of hair. Trichilemmal cysts are
      common over scalp and present as dermal or subcutaneous growths over scalp. We
      present a solitary schwannoma of scalp clinically mimicking trichilemmal cyst.
      The tumor was surgically excised and the same was confirmed by histopathology. 

PMID- 24082209
TI  - Palmar lichen planus mimicking tinea nigra.
AB  - Lichen planus (LP) is a chronic inflammatory skin disease characterized by
      polygonal, violaceous papules commonly involving flexural areas of the wrists,
      legs, and oral and genital mucous membranes. This report describes a patient who
      presented with asymptomatic black colored patches on both palms simulating Tinea
      nigra, a superficial fungal infection. She was previously diagnosed as allergic
      contact dermatitis and was being treated with potent topical steroid i.e.
      clobetasol propionate 0.05% and white soft paraffin. Dermatoscopy of the lesion
      showed brownish pigmentation along ridges of the dermatoglyphics. A biopsy from
      the lesional skin showed findings of lichen planus. Our case highlights the
      potential diagnostic confusion that can occur with unusual variants of
      palmoplantar lichen planus and importance of histopathology in diagnosis of such
      unusual lesions. 

PMID- 24082210
TI  - Transient idiopathic primary penoscrotal edema.
AB  - We present the case of a male born prematurely at 32 weeks gestation by cesarean
      section following overt symptoms of maternal preeclampsia. He developed severe
      penoscrotal edema anew one month from birth. No remarkable exposure or trauma was
      identified. This unexplained swelling remained uniform till 4 months of age,
      while the penile edema resolved spontaneously. A small benign hydrocele remained
      unchanged, since onset of the edema and continued after the edema subsided. This
      is the first report of persistent, but transient penoscrotal edema resolving in a
      3 months course, without any apparent explanation, a possible pathogenetic
      mechanism was suggested. 

PMID- 24082211
TI  - A rare case of familial reactive perforating collagenosis.
AB  - A 4 year old boy presented with history of itchy raised lesions on body of 2
      years duration. Though parental consanguinity was not present, his elder brother
      had similar complaints. Dermatological examination revealed multiple
      hyperpigmented papules with a central keratotic plug distributed mainly over face
      and extensors of upper and lower extremities. Koebnerisation was present. Skin
      biopsy revealed perforating collagen bundles in the upper dermis and epidermis
      which was confirmed by Van Gieson staining. Patient was being treated with
      topical retinoids and intralesional corticosteroids with minimal relief. 

PMID- 24082212
TI  - Chronic osteomyelitis of humerus presenting as scrofuloderma.
AB  - Scrofuloderma is a common type of cutaneous tuberculosis usually manifests over
      an infected lymphnode, bone or joint that breaks down to form an undermined ulcer
      leading to discharging sinuses. We present a case of a 22 year old woman with
      diffuse swelling of right arm with overlying nodulo ulcerative skin lesions
      associated with seropurulent discharge. Routine investigations were normal and X
      Ray of the right humerus showed the features of chronic osteomyelitis. Smears of
      the discharge for bacteria, fungi and acid fast bacilli were negative, but
      culture of skin biopsy showed Mycobacterium tuberculosis which was confirmed by
      PCR. Histopathology of skin biopsy showed epithelioid granulomatous inflammation
      suggestive of tuberculosis. After treating the patient with antitubercular
      therapy complete regression of the lesions occurred. 

PMID- 24082213
TI  - Nosocomial urinary tract aspergilloma in an immunocompetent host: an unusual
      occurrence.
AB  - Fungal infections of the urinary tract are usually encountered following
      prolonged antibiotic use, instrumentation and indwelling urinary catheters.
      Candida is the most frequent causative fungus. However, infections with
      Aspergillus flavus have been reported previously in immune-compromised hosts. We,
      hereby, report a 32-year-old immunocompetent man diagnosed to have urinary tract
      infection caused by Aspergillus flavus following instrumentation for the removal
      of a ureteric stone. The infection was symptomatic, associated with abdominal
      pain and subsequent passage of fungal masses per urethra. Patient was treated
      successfully with a prolonged course of broad spectrum antifungal agent
      itraconazole. 

PMID- 24082214
TI  - Nevoid Hyperkeratosis of the Nipple and/or Areola: Treatment with Topical
      Steroid.
AB  - Nevoid hyperkeratosis of the nipple and/or areola (NHNA) is a rare and benign
      disease, with poorly understood etiology and no definite therapeutic plan.
      Hereby, we report another case of NHNA, discuss about its clinical and
      histopathological features, differential diagnosis, and responsiveness to topical
      steroid. 

PMID- 24082215
TI  - Multiple familial trichoepithelioma with malignant transformation.
AB  - Trichoepithelioma (TE) is a benign tumor of follicular origin that presents as
      small, skin-colored papules predominantly on the face. When more than one family
      member is affected, the disease is known as multiple familial trichoepithelioma
      (MFT). It is a rare autosomal dominant (AD) skin disease. Malignant
      transformation is very rare. We present a case of MFT in a female patient and her
      father with malignant transformation to basal cell carcinoma (BCC) in the father.
      We summarized the main histological differential parameters between TE and BCC
      and applied immunophenotyping for both by administration of Bcl2, CD34, CD10 and
      androgen receptor (AR) antibodies. 

PMID- 24082216
TI  - Thrombosis warning in children suffering from henoch-schonlein purpura.
AB  - Henoch-Schonlein Purpura (HSP) is one of the most common types of vasculitis in
      children. The characteristic clinical manifestations include non-thrombocytopenic
      purpura, arthritis or arthralgia, abdominal pain, gastrointestinal hemorrhage and
      renal abnormalities. Thrombosis has been reported as, a rare complication of HSP.
      We present the case of a 14-year-old boy who was diagnosed with HSP and suspected
      superior mesenteric vein thrombosis. We reviewed the relevant literature and
      found eight similar reported cases. HSP is associated with thrombosis and HSP
      itself and some risk factors may result in thrombosis. We suggest that physicians
      should monitor patients with HSP who are at a higher risk of developing
      thrombosis more closely. 

PMID- 24082217
TI  - An unusual presentation of sporotrichosis.
AB  - Sporotrichosis can mimic a few diseases. Sporotrichosis presenting as a
      hypoaesthetic plaque or plaque suggestive of leprosy has not been mentioned in
      literature. Herein we present a case of a 26 years old man who presented with
      hypoesthetic plaque on left ankle and was clinically diagnosed to have borderline
      tuberculoid leprosy who later developed few nodules in linear fashion on left
      leg, which ruptured to form non healing ulcers. Culture from ulcer grew
      Sporothrix schenckii. Patient was successfully treated with oral potassium
      iodide. 

PMID- 24082218
TI  - Isolated, localised extragenital bullous lichen sclerosus et atrophicus: a rare
      entity.
AB  - Lichen sclerosus et atrophicus (LSA) is a rare, chronic, mucocutaneous disease of
      unknown cause. Onset can occur in subjects of any age but more prevalent in adult
      females around the time of menopause. In both the sexes anogenital involvement is
      more common. Extragenital cases are rare, and common localizations are neck and
      shoulders, axilla, upper arms, flexor aspects of wrists and around the umbilicus.
      Bullous LSA is an unusual manifestation of the disease. Isolated extragenital
      bullous LSA is a distinctly rare event with very few cases reported till date. 

PMID- 24082219
TI  - Linear syringocystadenoma papilliferum: a case report with review of literature.
AB  - We report a rare case of syringocystadenoma papilliferum (SCAP) presenting as
      multiple papulonodules in a linear pattern over right lower abdomen which has
      been reported only once before. 

PMID- 24082220
TI  - Cutaneous benign epithelioid peripheral nerve sheath tumour: a rare entity.
AB  - Benign epithelioid peripheral nerve sheath tumor, a rare entity is an umbrella
      term describing benign, neural origin tumors with epithelioid morphology.
      Clinically indistinguishable from other benign cutaneous lesions, histopathology
      offers the only source of accurate diagnosis. Morphologic mimics include many
      benign and malignant soft tissue lesions. Besides a predominant epithelioid
      component, the lesion can also show a fair share of spindle cells. A
      circumscribed nodular tumour of low mitotic activity, it often exhibits areas
      resembling schwannoma or neurofibroma. An awareness of this entity and its varied
      morphological aspects helps to arrive at the correct diagnosis and hence avoid
      unnecessary extensive surgical procedures. This case presents features of this
      benign tumor which occurred in a 47 years old man. 

PMID- 24082221
TI  - Spongiotic intra-epidermal blister: a pitfall in the histopathologic diagnosis of
      bullous pemphigoid.

PMID- 24082222
TI  - Paederus dermatitis: an outbreak, increasing incidence or changing seasonal
      pattern?

PMID- 24082223
TI  - Foamy discharge on the scalp of the infant: munchausen syndrome by proxy.

PMID- 24082224
TI  - Dapsone Induced Methemoglobinemia and Hemolysis in a G6PD Deficient Girl,
      Possibly Aggravated by Aggressive Methylene Blue Therapy.

PMID- 24082225
TI  - Papillon-lefevre syndrome: two siblings, one developing liver abscess.

PMID- 24082226
TI  - LEOPARD syndrome with rare skeletal anomalies: A case report.

PMID- 24082227
TI  - Favus in an elderly Kashmiri female: A rare occurrence.

PMID- 24082228
TI  - A case of Juvenile Xanthogranuloma in the Nasal Cavity of a Neonate.

PMID- 24082229
TI  - Cutaneous hyalohyphomycosis in an immunocompetent host.

PMID- 24082230
TI  - Isolated pedunculated collagenoma (collagen nevi) of the scalp.

PMID- 24082231
TI  - Zosteriform morphea in an immunocompetent patient.

PMID- 24082232
TI  - Familial syringomas.

PMID- 24082233
TI  - A case of verrucous carcinoma on the finger.

PMID- 24082234
TI  - Hailey-hailey disease on sun-exposed areas.

PMID- 24082235
TI  - Hypopigmented papules over the chest.

PMID- 24082236
TI  - Ulcerative nodule on a chronic discoid lupus erythematosus lesion.

PMID- 24082237
TI  - Dark age vampires or our poor patients.

PMID- 24082238
TI  - Sexual coercion: Time to rise to the challenge.

PMID- 24082239
TI  - Childhood sexual abuse and the law: More problems than solutions?

PMID- 24082240
TI  - Time to face new realities; mental health care bill-2013.

PMID- 24082241
TI  - Diagnostic and statistical manual of mental disorders 5: A quick glance.

PMID- 24082242
TI  - Resilience: Building immunity in psychiatry.
AB  - The challenges in our personal, professional, financial, and emotional world are
      on rise, more so in developing countries and people will be longing for mental
      wellness for achieving complete health in their life. Resilience stands for one's
      capacity to recover from extremes of trauma and stress. Resilience in a person
      reflects a dynamic union of factors that encourages positive adaptation despite
      exposure to adverse life experiences. One needs to have a three-dimensional
      construct for understanding resilience as a state (what is it and how does one
      identify it?), a condition (what can be done about it?), and a practice (how does
      one get there?). Evaluating the level of resilience requires the measurement of
      internal (personal) and external (environmental) factors, taking into account
      that family and social environment variables of resilience play very important
      roles in an individual's resilience. Protection factors seem to be more important
      in the development of resilience than risk factors. Resilience is a process that
      lasts a lifetime, with periods of acquisition and maintenance, and reduction and
      loss for assessment. Overall, currently available data on resilience suggest the
      presence of a neurobiological substrate, based largely on genetics, which
      correlates with personality traits, some of which are configured via social
      learning. The major questions about resilience revolve around properly defining
      the concept, identifying the factors involved in its development and recognizing
      whether it is actually possible to immunize mental health against adversities. In
      the clinical field, it may be possible to identify predisposing factors or risk
      factors for psychopathologies and to develop new intervention strategies, both
      preventive and therapeutic, based on the concept of resilience. The preferred
      environments for application of resilience are health, education, and social
      policy and the right approach in integrating; it can be developed only with more
      research and analysis with focus on resilience. Be it patient or family member or
      caregiver, advocating resilience will empower psychiatrists in India. 

PMID- 24082243
TI  - Mental health assessment of rape offenders.
AB  - There is an urgent need for development of methods of assessment and management
      of sex offenders (rapists, child sex offenders, other sexual offenders, and
      murderers) to mount a society-wide battle against the scourge of sexual offences
      in India. This paper provides an overview of theories, models, and assessment
      methods of rapists. It draws upon literature from psychiatry, psychology,
      criminology, probation, and ethics to provide a framework for understanding
      reasons behind rape, how mental health issues are implicated, what mental health
      professionals can do to contribute to crime management, and why this is ethically
      right and proper. 

PMID- 24082244
TI  - Sexual violence against women: Understanding cross-cultural intersections.
AB  - Interpersonal violence whether it is sexual or nonsexual, remains a major problem
      in large parts of the world. Sexual violence against children and women brings
      with it long-term sequelae, both psychiatrically and socially. Apart from sexual
      gratification itself, sexual violence against women is often a result of unequal
      power equations both real and perceived between men and women and is also
      strongly influenced by cultural factors and values. Within sociocentric and ego
      centric cultures, the roles and representations of genders, and attitudes toward
      sexual violence differ. Cultures which are described as feminist, provide equal
      power to both men and women. Sexual violence is likely to occur more commonly in
      cultures that foster beliefs of perceived male superiority and social and
      cultural inferiority of women. Although culture is an important factor to
      understand sexual violence in its entirety, we need to look at, as well as beyond
      cultural structures, their strengths and weaknesses. 

PMID- 24082245
TI  - Rape: Legal issues in mental health perspective.
AB  - Rape of women by men has occurred throughout recorded history and across cultures
      and religions. It is a crime against basic human right and a most common crime
      against women in India. In this article, rape is discussed from legal and mental
      health perspective. In India 'rape laws' began with enactment of Indian Penal
      Code in 1860. There have been subsequent amendments and the main issue of focus
      remained the definition of 'rape and inclusion of 'marital rape' in the ambit of
      rape. Law Commission Reports related to rape and the psychological impacts of
      rape have been discussed. 

PMID- 24082246
TI  - Bereavement after the suicide of a significant other.
AB  - CONTEXT: It is estimated that approximately one in four people know someone who
      has taken their own life and that one suicide death leaves six or more suicide
      survivors. AIMS: The aim of this paper was to review the literature regarding the
      association between suicide and bereavement, focusing also on the supportive and
      therapeutic resources available for survivors. MATERIALS AND METHODS: Careful
      MedLine and PsycINFO searches for the period 1980-2013. RESULTS: The review of
      the literature indicates that emotional turmoil in suicide survivors may last a
      long time and, in some cases, may end with their own suicide. CONCLUSION: Future
      research should evaluate the efficacy of professional treatments and of support
      groups targeting suicide survivors. PRACTICE IMPLICATIONS: It is crucial to
      understand the bereavement process after the suicide of a significant other in
      order to provide proper care, reduce stigma, and improve the outcomes of related
      psychiatric conditions.

PMID- 24082247
TI  - A study of neuropsychiatric manifestations in patients of neurocysticercosis.
AB  - BACKGROUND: Neurocysticercosis (NCC) is an endemic parasitic infection of Asia,
      Africa, Latin America, and central Europe. Neuropsychiatric manifestations of the
      illness include epilepsy and behavioral disturbances. There is a dearth of
      systematic studies on psychiatric manifestations of NCC from various Asian
      counties. The present study assessed the prevalence of various psychiatric
      disorders in a cohort of patients with NCC attending a neurological service.
      MATERIALS AND METHODS: Detailed psychiatric assessment was carried out on 50
      patients of NCC with epilepsy and 50 patients of epilepsy without any evidence of
      NCC. Comprehensive Psychopathological Rating Scale was used to elicit the
      symptoms. Cognitive functions were assessed using Mini Mental Status Examination.
      Psychiatric diagnoses were made as per International Classification of Diseases,
      10(th) edition (ICD-10). RESULTS: Sixty eight percent of the patients with NCC
      suffered from a psychiatric disorder, as compared to 44% of those without NCC
      (P=0.02). Major depression and mixed anxiety depression were the two most common
      diagnoses. None of the patients was to found to suffer from a psychotic disorder.
      The most frequent site of brain lesion of NCC was the parietal lobe, followed by
      frontal lobes and disseminated lesions. Left sided lesions were associated with
      greater psychiatric morbidity. Focal seizures with or without secondary
      generalizations were present more frequently in patients with NCC whereas primary
      generalized seizures were more common in patients with idiopathic epilepsy
      (P=0.05). CONCLUSION: Psychiatric manifestations are more common in patients of
      epilepsy with NCC than those without NCC. The treating clinician need to be
      vigilant about the phenomenon.

PMID- 24082248
TI  - Psychological attributes and socio-demographic profile of hundred completed
      suicide victims in the state of Goa, India.
AB  - AIMS: To describe socio-demographic characteristics, psycho-social factors,
      psychiatric co-morbidity in hundred completed suicide victims. MATERIALS AND
      METHODS: A detailed interview was carried out with family members of suicide
      victims using psychological autopsy questionnaire. RESULTS: Males committed
      suicide significantly more often than females. The most common age group was 30
      44 years, followed by 15-29 years. Most of them were married (68%) and majority
      (78%) had education less than 10(th) standard. Psychiatric morbidity was found in
      94%, depression being the most common diagnosis (54%), followed by alcohol use
      disorders (42%). 40% of the victims had contact with mental health services and
      50% with general health services in the 3 months preceding suicide. CONCLUSIONS:
      The rate of suicide is high in middle age and a very significant proportion of
      these suffer from diagnosable psychiatric disorders. Many of the suicide
      completers visit health services in the preceding few months of the event. In
      prevention of suicides, health professionals, both mental and general, can play a
      major role.

PMID- 24082249
TI  - Factors associated to depression in renal transplant recipients in Panama.
AB  - AIM: High rates of affective disorders have been reported in kidney transplant
      recipients treated for end-stage renal disease. Latin America has experienced a
      significant increase in transplant activity in recent decades, but there is a
      dearth of data regarding psychosocial issues following kidney transplantation.
      The aim of this study was to measure the prevalence of depression and the
      demographic factors associated to depression among renal transplant recipients in
      Panama. MATERIALS AND METHODS: This cross-sectional study was conducted between
      March to May 2010 in a hospital setting during routine outpatient evaluations.
      The study included 119 renal transplant recipients (58 males, 61 females).
      Depressive symptoms were measured using the self-report Hospital Anxiety and
      Depression Scale and diagnoses were established by a trained psychiatrist using
      the Mini-International Neuropsychiatric Interview. Regression models were used to
      explore the association between depression and sociodemographic variables.
      RESULTS: The prevalence of depression was 11.8% among transplant recipients.
      Linear regression indicated that the presence of an anxiety disorder, increasing
      age, and lower education levels were significantly and independently associated
      with depressive symptoms. Logistic regression analysis confirmed that anxiety and
      a perception of negative social support significantly increased the likelihood of
      depression. CONCLUSIONS: These findings have important clinical implications.
      Depression after kidney transplantation has been shown to affect health outcomes
      adversely. Our results underscore the need to assess depressive symptoms as well
      as other affective disorders as part of the screening and treatment of renal
      transplant patients in Panama.

PMID- 24082250
TI  - Clinical validity of NIMHANS neuropsychological battery for elderly: A
      preliminary report.
AB  - BACKGROUND: Neuropsychological assessment plays a crucial role in the assessment
      of cognitive decline in older age. In India, there is a dearth of culturally
      appropriate standardized measure to assess cognitive functions in early dementia.
      The aim of the study was to examine clinical validity of NIMHANS
      Neuropsychological Battery for Elderly (NNB-E) in identifying early dementia.
      OBJECTIVES: To examine validity (discriminant and concurrent) of NIMHANS
      Neuropsychological Battery for Elderly (NNB-E). RESULTS: Participants with AD
      showed significantly poorer performance on every test including memory and non
      memory domains. However, tests of episodic and semantic memory were particularly
      sensitive in discriminating between normal and AD groups. Further scores on
      various subtests in the NNB-E were positively associated with scores on HMSE and
      negatively associated with Clinical Dementia Rating and Everyday Abilities Scale
      for India (EASI) scores. CONCLUSIONS: NNB-E was able to differentiate normal
      controls from AD patients, and it can therefore be an ecologically valid tool for
      Indian older adults.

PMID- 24082251
TI  - A psychometric cut-point to separate emergently suicidal depressed patients from
      stable depressed outpatients.
AB  - CONTEXT: The design of safe clinical trials targeting suicidal ideation requires
      operational definitions of what degree of suicidal ideation is too excessive to
      allow safe participation. AIMS: We examined the Scale for Suicide Ideation (SSI)
      to develop a psychometric cut-point that would identify patients having a
      suicidal emergency. SETTINGS AND DESIGN: The Emergency Department (ED) and the
      out-patient clinic of a university hospital. MATERIALS AND METHODS: We used the
      SSI to contrast 23 stable, depressed adult out-patients versus 11 depressed adult
      ED patients awaiting psychiatric admission for a suicidal emergency. STATISTICAL
      ANALYSIS: The performance of the SSI was examined with nominal logistic
      regression. RESULTS: ED patients were older than out-patients (P<0.001), with
      proportionally more men (P<0.05), and were more ethnically diverse than the
      outpatients (P<0.005). Compared to out-patients, ED patients were more depressed
      (Patient Health Questionnaire-9 score 23.1+/-3.8 vs. 11.7+/-7.3, P<0.005) and
      reported a greater degree of suicidal ideation (SSI scores 25.7+/-7.3 vs. 4.2+/
      8.4, P<0.0001). Nominal logistic regression for the univariate model of SSI score
      and group yielded a score of 16 (P<0.0001) as the best cut-point in separating
      groups, with a corresponding Receiver Operating Characteristic Area Under the
      Curve = 0.94. Of 34 patients in the total sample, only two were misclassified by
      SSI score = 16, with both of these being false positive for ED status. Thus, the
      sensitivity of the cut-point was 100% with specificity of 91%. When the model was
      expanded to include SSI along with age, gender, ethnicity, sedative-hypnotic use,
      and over-the-counter use, only SSI score remained significant as a predictor.
      CONCLUSIONS: A SSI score >=16 may be useful as an exclusion criterion for out
      patients in depression clinical trials.

PMID- 24082252
TI  - Depression and type D personality among undergraduate medical students.
AB  - CONTEXT: Academic pressure, though established, is an unavoidable cause of
      depression in medical students. Role of Type D personality as determinant of
      depression is a new approach to the problem. AIM: Determination of relationship
      between Type D personality and Depression among medical students. SETTING AND
      DESIGN: Undergraduate students (both male and female, total 150) of Midnapore
      Medical College. MATERIALS AND METHODS: Beck Depression Inventory for depression
      and DS 14 for type D personality. STATISTICAL ANALYSIS: The scores were expressed
      as mean + SD. The significance of difference between the scores was done by
      Fisher's 2 sample t test. RESULTS AND CONCLUSION: Prevalence rate of depression
      was 45.3%, which was mostly of mild type (34%). Type D personality was present in
      70% cases of which 15.3% had only negative affectivity, 23.3% had only social
      inhibition and 31% had both the components. Both depression & Type D personality
      were present in 36% cases. Negative affectivity component was significantly
      associated with depression which could be therapeutically controlled.

PMID- 24082253
TI  - A case of Zolpidem dependence successfully detoxified with gabapentin.
AB  - An elderly female patient with Zolpidem dependence, who was successfully
      detoxified using Gabapentin is reported. Gabapentin may be considered as an
      alternative in the detoxification of non-benzodiazepine hypnotics. 

PMID- 24082254
TI  - A patient with Tramadol dependence and predictable provoked epileptic seizures.
AB  - Tramadol is an atypical, centrally acting synthetic analgesic with propensity for
      provoked seizures as well as abuse potential. The index case of Tramadol
      dependence discussed in this case report developed multiple epileptic seizures
      with high doses of Tramadol, used as a sexual enhancer by him, and later he
      learned to prevent the seizures by self-medicating with Alprazolam. The authors
      further emphasize on the regulation of Tramadol prescription. 

PMID- 24082255
TI  - Literary destigmatisation of mental illness: A study of the writings of
      Jayakanthan.
AB  - National and international associations of psychiatry are busy formulating and
      executing anti-stigma measures and activities. Literary works of creative artists
      could be utilised for this purpose. This article based on the writings of a
      popular Tamil writer Jayakanthan discusses some of his works in relation to this.

PMID- 24082256
TI  - Child psyche.

PMID- 24082257
TI  - Child psychopharmacology: Is it more similar than different from adult
      psychopharmacology?
AB  - Despite having a large chunk of human population, Asian countries face shortage
      of mental health professionals. There is further shortage of doctors dealing with
      special groups of population like the children, the elderly, and the medically
      ill. However, in this era of super-specializations, are the basic principles of
      general psychopharmacology being forgotten? Dealing with child population is
      different and often more difficult than adult population but are management
      guidelines for the two populations vastly divergent? A close look at this paints
      a different picture. Psychotherapies applied in adults and those in children and
      adolescents are disparate owing to cognitive, social, emotional, and physical
      immaturation in children and adolescents. But the drugs for the treatment of
      pediatric psychiatric disorders are mostly similar to those prescribed for adults
      (case in point -bipolar disorders, obsessive compulsive disorder, schizophrenia).
      Rather than focusing energy on propagating the differences in assorted subgroups
      of population, honing of skills regarding intricacies of psychopharmacology is
      required to be emphasized. Detailed history taking, careful evaluation of the
      patient, sound diagnostic formulation, and prescribing medications which are
      tailor made to the patient will all go a long way in ensuring a functional
      recovery of the patients irrespective of the group they belong to. 

PMID- 24082258
TI  - Atypical presentation of dystonia in a polydrug user.

PMID- 24082259
TI  - Response to article: The manpower development scheme under the National Mental
      Health Program.

PMID- 24082260
TI  - Indian contribution to the cultural formulation interview and the DSM-5: Missing
      details from the position paper.

PMID- 24082261
TI  - Reply to Indian contribution to the cultural formulation interview and the DSM-5:
      Missing details from the position paper.

PMID- 24082262
TI  - Potential use of peanut by-products in food processing: a review.
AB  - Peanut is one of the most important oil and protein producing crops in the world.
      Yet the amounts of peanut processing by-products containing proteins, fiber and
      polyphenolics are staggering. With the environmental awareness and scarcity of
      space for landfilling, wastes/by-product utilization has become an attractive
      alternative to disposal. Several peanut by-products are produced from crush
      peanut processes and harvested peanut, including peanut meal, peanut skin, peanut
      hull and peanut vine. Some of peanut by-products/waste materials could
      possibility be used in food processing industry, The by-products of peanut
      contain many functional compounds, such as protein, fiber and polyphenolics,
      which can be incorporated into processed foods to serve as functional
      ingredients. This paper briefly describes various peanut by-products produced, as
      well as current best recovering and recycling use options for these peanut
      byproducts. Materials, productions, properties, potential applications in food
      manufacture of emerging materials, as well as environmental impact are also
      briefly discussed. 

PMID- 24082263
TI  - Cactus: a medicinal food.
AB  - With excellent quality and flavour of fresh fruits, young leaves of cactus serve
      as nutritious vegetable and salad dish and the immature fruits for making mock
      gherkins. Cactus, with high water use efficiency produce forage for animals,
      vegetables, and fruits with 14% glucose. Traditionally cactus used as a valuable
      health supporting nutrient and it also has applications in pharmaceutical
      industries. Cactus with number of uses has immense potential to be the food of
      future. 

PMID- 24082264
TI  - Optimization of the biological processing of rice dregs into nutritional peptides
      with the aid of trypsin.
AB  - A protein hydrolysate was prepared from rice dregs (RD) using trypsin as a
      suitable protease. The hydrolysis conditions were optimized with response surface
      methodology, and then a mathematical model was developed to demonstrate the
      effect of each process parameter on the degree of hydrolysis (DH) and recovery of
      protein (RP). A hydrolysate with relatively high RP (75.81%) and low DH (6.95)
      was obtained from RD by hydrolyzing for 2.4 h at pH 7.6 52.8 degrees C with a
      enzyme/RD ratio of 0.89:1000 (w/w) and RD/water level of 0.22 g/mL. The dried
      hydrolysate was low molecular weight peptides (predominantly <1,000 Da) and it
      possessed good solubility at various pH levels. Result of amino acid analysis
      revealed that the hydrolysate was considerably enriched in essential amino acids.
      Thus, the protein hydrolysate has a potential to be an excellent protein
      ingredient as a balanced milk replacer. 

PMID- 24082265
TI  - Optimization of osmotic dehydration conditions of peach slices in sucrose
      solution using response surface methodology.
AB  - Osmotic dehydration (OD) conditions of peach slices were optimized using response
      surface methodology (RSM) with respect to sucrose concentration (50-70 degrees
      B), immersion time (2-4 h) and process temperature (35-55  degrees C) for maximum
      water loss (WL), minimum solute gain (SG) and maximum rehydration ratio (RR) as
      response variables. A central composite rotatable design (CCRD) was used as
      experimental design. The models developed for all responses were significant. All
      model terms were significant in WL except the quadratic levels of sucrose
      concentration and temperature whereas in SG, linear terms of time and linear and
      quadratic terms of temperature were significant. All the terms except linear term
      of time and interaction term of time and sucrose concentration, were significant
      in RR. The optimized conditions were sucrose concentration = 69.9 degrees B, time
      = 3.97 h and temperature = 37.63  degrees C in order to obtain WL of 28.42 (g/100
      g of fresh weight), SG of 8.39 (g/100 g of fresh weight) and RR of 3.38. 

PMID- 24082266
TI  - Extension of shelf life of pear fruits using different packaging materials.
AB  - An experiment was conducted on pear fruit (cv. 'Lagoon') to extend the shelf life
      by using different packaging materials. Fruits were packed in low density
      polyethylene (LDPE, 0.025 mm), polypropylene (PP, 0.025 mm), linear low density
      polyethylene (LLDPE, 0.0125 mm) and high density polyethylene (HDPE, 0.025 mm)
      with or without perforation and stored at ambient condition (25 +/- 2  degrees C
      and 65.0 +/- 5% RH). Periodical observations were recorded on CO2 & O2
      concentration (%), physiological loss in weight (PLW, %), decay loss (%),
      firmness (kgf), colour value (colour difference and colour index), total soluble
      solid (TSS,  degrees Brix), acidity (mg of malic acid/g), and ascorbic acid loss
      (%) at 3 days interval. Reduced rate of PLW and decay losses was recorded in pear
      fruits packed in PP non-perforated (8.04%) and PP perforated (12.5%),
      respectively as compared to other treatments. The maximum firmness (5.18 kgf) and
      minimum ascorbic acid loss (49.97%) were also recorded in PP non-perforated up to
      12 and 15 days of storage, respectively. It could be inferred that the, PP non
      perforated (0.025 mm) was the most suitable packaging materials for extending the
      shelf life of pear fruits up to 15 days at ambient condition. 

PMID- 24082267
TI  - Bacteriology of a most popular street food (Panipuri) and inhibitory effect of
      essential oils on bacterial growth.
AB  - Bacteriology of Panipuri was studied and the antibacterial effect of eight
      essential oils (EOs) was established on pathogens found in Panipuri. Samples were
      collected from twelve respective vendors from different locations in Baripada
      city, Orissa. Samples were fractionated into two parts viz. khatta pani and
      smashed potato masala used in Panipuri. Total plate count and isolation of
      pathogenic bacteria were done on both basal and selective media. Coliforms were
      detected primarily by presumptive test and confirmed subsequently, using Eosine
      Methylene Blue Agar. Selected colonies were pure cultured and identified through
      staining and an array of biochemical reactions. Antibiogram pattern of the
      pathogens and their susceptibility towards eight different EOs were performed.
      Antibacterial efficacy of four EOs in food sample was studied. Aerobic bacterial
      load of solid samples was observed to be more than in the liquid samples.
      Coliform-positive samples were found to be of 80.33%. Pathogenic bacteria like
      Escherichia coli, Klebsiella sp., Enterobactor sp., Bacillus sp., Enterococcus
      sp., Micrococcus tetragens, Salmonella paratyphi, Shigella dysenteriae and Vibrio
      sp. were detected. Antibiogram studies of the isolates showed multiple antibiotic
      resistance index (MRI;%) ranging from 15 to 92%. Among the EOs studied Cinnamon
      and Clove oils showed maximum antibacterial activity. Antibacterial efficacy
      showed that Clove and Cinnamon oils were comparatively of superior quality than
      Turmeric leaf and Japanese mint oils to kill food borne pathogens. Although it
      was a preliminary endeavor, the present study is a prerequisite in understanding
      the significance of pathogenic microorganisms in street foods and use of EOs as
      both antibacterial agents and food preservatives. 

PMID- 24082268
TI  - Effect of selected dehulled legume incorporation on functional and nutritional
      properties of protein enriched sorghum and wheat extrudates.
AB  - The effect of legume incorporation (5%, 10% and 15%) on functional and
      nutritional properties of sorghum and wheat extrudates was investigated. Sorghum
      extrudates incorporated with legumes showed lower water absorption index water
      solubility index and pasting properties viz., peak viscosity, minimum viscosity,
      breakdown viscosity, final viscosity and total set back and similar degree of
      gelatinization and nutritional profile. At 15% incorporation level, water
      absorption index and water solubility index found to be maximum while degree of
      gelatinization and all the pasting properties showed lowest values for both
      sorghum and wheat extrudates. Similarly nutritional profile observed to be
      significantly higher for 15% as compared to 10% and 15% incorporation levels.
      Incorporation of legumes at 15% could be effective in producing high energy dense
      food products having better functional and nutritional properties. 

PMID- 24082269
TI  - Effect of incorporation of corn byproducts on quality of baked and extruded
      products from wheat flour and semolina.
AB  - The effect of blending level (0, 5, 10, 15 and 20%) of corn bran, defatted germ
      and gluten with wheat flour on the physico-chemical properties (protein, crude
      fiber, phosphorus, iron and calcium), baking properties of bread, muffins and
      cookies, and extrusion properties of noodles and extruded snacks prepared from
      semolina were examined. Blending of wheat flour and corn byproducts significantly
      increased the protein, crude fiber, phosphorus, iron and calcium contents. Breads
      from gluten blends had higher loaf volume as compared to bran and germ breads.
      Among corn byproducts, gluten cookies were rated superior with respect to top
      grain. Muffins from germ blends and gluten blends had higher acceptability scores
      than the bran muffins. Blending of corn bran, defatted germ and gluten at 5 and
      10% with wheat flour resulted in satisfactory bread, cookie, and muffin score.
      Quality of noodles was significantly influenced by addition of corn byproducts
      and their levels. Corn byproducts blending had significant influence on cooking
      time, however, gruel solid loss affected non-significantly in case of noodles.
      Expansion ratio and density of extruded snacks was affected non significantly by
      blending source and blending level. However, significant effect was observed on
      amperage, pressure, yield and overall acceptability of extruded snacks.
      Acceptable extruded products (noodles and extruded snacks) could be produced by
      blending corn byproducts with semolina upto 10% level. 

PMID- 24082270
TI  - Rheology, fatty acid profile and storage characteristics of cookies as influenced
      by flax seed (Linum usitatissimum).
AB  - Flaxseed is a versatile functional ingredient owing to its unique nutrient
      profile. Studies on the effect of substitution of roasted and ground flaxseed
      (RGF) at 5, 10, 15 and 20% level on the wheat flour dough properties showed that
      amylograph peak viscosity, farinograph dough stability, extensograph resistance
      to extension and extensibility values decreased with the increase in the
      substitution of RGF from 0-20%. The cookie baking test showed a marginal decrease
      in spread ratio but beyond substitution of 15% RGF the texture and flavour of the
      cookies was adversely affected. The data on storage characteristics of control
      and cookies with 15% RGF showed no significant change with respect to acidity of
      extracted fat and peroxide values due to storage of cookies upto 90 days in
      metallised polyester pouches at ambient conditions. The gas chromatographic
      analysis of fatty acid profile indicated that the control cookies contained
      negligible linolenic acid and the flaxseed cookies contained 4.75 to 5.31% of
      linolenic acid which showed a marginal decrease over storage. Hence flaxseed
      could be used as a source of omega-3-fatty acid. 

PMID- 24082271
TI  - Physico-chemical quality parameters and overall quality index of apple during
      storage.
AB  - Physico-chemical quality parameters of apple were measured during storage using
      standard techniques and fitted to model expressions for developing an overall
      quality index (Iq). Predicted Iq was validated with the trends of sensory scores.
      Total Soluble Solids (TSS) and acidity varied from 13.2 to 12.3 oBrix and 0.161
      to 0.079%, respectively whereas, Hunter colour values L, a, b and yellowness
      index were 48.7-56.1, 11.0-19.4, 18.8-20.2 and 84.6-98.2, respectively. The gloss
      at 45 and 60o incidence angles, density and Iq varied from 7.5 to 4.3 and 6.7 to
      2.6 GU, 1.01 to 0.96 kg m(-3) and 0.26 to 1.02, respectively. The variation in
      sensory overall quality scores with storage period was found to be in line with
      computed overall quality index. The Iq thus, could be defined as the ratio of
      product of acidity and TSS to the mode of product of a and b Hunter colour
      values. The polynomial regression equations for Iq with TSS, acidity, a, b, and
      storage period yielded the correlation coefficients of 0.8443, 0.9838, 0.7130,
      0.7183 and 0.9665, respectively; which indicated that overall quality index could
      be predicted nondestructively using any one of these parameters during storage. 

PMID- 24082272
TI  - Fate of some pathogenic bacteria and molds in Turkish Tarhana during fermentation
      and storage period.
AB  - The survival of the molds and some pathogenic bacteria such as E. coli O157:H7,
      S. aureus, S. typhimurium and B. cereus during fermentation and storage period of
      tarhana (traditional Turkish fermented food) was investigated. Tarhana batches
      were produced with two different yogurt/flour ratio 0.5 (T1) and 0.75 (T2). The
      pH and Eh values of samples were around 4.0-4.5 and 130-160 mV during
      fermentation and storage period in both batches, respectively. Moisture and aw
      values in T1 and T2 samples significantly decreased (p < 0.05) between the 3rd
      7th days of production at 11.2-11.6% and 0.52-0.54, respectively. The numbers of
      S. aureus and S. typhimurium significantly decreased (p < 0.05) during the 1st
      and 2nd days of fermentation period, respectively and this decline gradually
      proceeded in both batches. No significant differences (p > 0.05) were observed in
      both tarhana batches among the molds, E. coli O157:H7 counts during the 1st, 2nd
      days of fermentation, and B. cereus counts during the all days of fermentation
      and storage periods, except the16th day of storage. 

PMID- 24082273
TI  - Kinetics of potato drying using fluidized bed dryer.
AB  - The effect of air temperature and two different shapes (cuboidal and cylindrical)
      with 3 aspect ratio of each shape on the drying kinetics of potato (Solanum
      tuberosum) in fluidized bed dryer was investigated. Drying was carried out at 50,
      60 and 70 degrees C at 7 m/s air velocity. Drying data were analysed to obtain
      effective diffusivity of moisture transfer. During drying moisture transfer from
      potato were described by Fick's diffusion model. Two mathematical models were
      fitted to experimental data. The Page model gave better fit than simple
      exponential model. The Arrehnious activation energy value expresses the effect of
      temperature on diffusivity. 

PMID- 24082274
TI  - Comparison of ethanol production from cheese whey permeate by two yeast strains.
AB  - The objective of the present laboratory scale experiment was to compare ethanol
      production by Kluyveromyces marxianus strain ATCC8554 and Candida kefyr ATCC
      14245 from unconcentrated and concentrated cheese whey permeate. The results
      indicated that ethanol production was greater when using concentrated whey
      permeate (9.8% lactose) compared to unconcentrated whey permeate (4.9% lactose)
      by both the yeasts, especially in presence of growth supplements. The rate and
      extent of ethanol formation increased noticeably and partly linearly for both the
      yeasts with sharp and partly linear decrease in both lactose and Chemical Oxygen
      Demand (COD), especially after the first 10 h of fermentation; total time of
      fermentation was 60 h. The optimum pH and temperature conditions for ethanol
      production were 4.8 and 30o C respectively. Klu. marxianus strain had greater
      ethanol producing ability from cheese permeate whey than Can. kefyr. 

PMID- 24082275
TI  - Quality evaluation of mutton Harrisa during one week refrigerated storage.
AB  - Harrisa is a popular indigenous meat based product of Jammu and Kashmir. An
      attempt was made to standardize the basic formulation and processing conditions
      for the preparation of the Harrisa using mutton meat. The product so developed
      was packed in low density polyethylene pouches (LDPE) and evaluated for a shelf
      life of 1 week at refrigeration (4 +/- 1 degrees C) temperature for various
      physicochemical, microbiological and sensory attributes. The mean values of pH,
      protein percent, fat percent and ash percent of the product increased
      significantly (P < 0.05) whereas the mean moisture percent showed a significantly
      (P < 0.05) decreasing trend during refrigerated storage. The mean scores of all
      the sensory parameters decreased significantly (P < 0.05) with storage. Total
      plate count and psychrophilic count increased significantly (P < 0.05) whereas
      the coliforms were not detected throughout the period of storage. Thiobarbituric
      acid reacting substances (TBARS) and free fatty acid (% oleic acid) values also
      increased significantly (P < 0.05) with storage period. Although storage resulted
      in significant decrease in almost all the quality attributes and sensory scores
      but the changes were within the limits of acceptability. The product was
      acceptable for a period of one week under refrigerated conditions. 

PMID- 24082276
TI  - Production and characterization of alkaline protease from hemoglobin-degrading
      Bacillus pumilus NJM4 to produce fermented blood meal.
AB  - The aim of the research was to isolate the hemoglobin-degrading bacterial strain
      to produce fermented blood meal and to characterize the protease produced by this
      strain. The strain NJM4, a kind of hemoglobin-degrading bacterial strain, was
      isolated by blood agar plates from slaughterhouse and identified as a Bacillus
      pumilus by physiological, biochemical, and morphological characteristics and by
      16S rRNA gene sequencing. Bacillus pumilus NJM4 could degrade hemoglobin up to
      85% in 36 h under the laboratory conditions. The optimal conditions for protease
      production was achieved at an initial pH level of 8.67, inoculum size of 4%,
      incubation temperature of 37  degrees C, and agitation rate 200 rpm. The optimum
      pH and temperature of hemoglobin-degrading proteases were at 9.0 and 50  degrees
      C, respectively. The protease activity was slightly decreased in presence of
      Ca(2+) and DTT. It was significantly inhibited in the presence of PMSF and EDTA
      identifying it as alkaline serine-metalloproteinase. Bacillus pumilus NJM4 and
      hemoglobin-degrading proteases provide potential use for biotechnological process
      of fermentation and enzymolysis blood meal as animal feed supplement. 

PMID- 24082277
TI  - Rheological and nutritional quality of selected dehulled legumes blended rice
      extrudates.
AB  - Rheological and nutritional quality of ready-to-eat rice (Oryza sativa ) -legume
      viz. black gram (Vigna mungo), green gram (Vigna radiata), lentil (Lens
      culinaris) and peas (Pisum sativum) based extrudates were studied using low cost
      collet extruder. Extrudates were prepared keeping constant feed rate (25 kg/h)
      and moisture content (14% wb) at 0, 5, 10 and 15% legume incorporation levels.
      Rheological properties of porridge made of extrudate flour were evaluated using
      Rapid Visco Analyser (RVA). Maximum and minimum peak viscosity for rice
      extrudates alone and rice extrudates blended with 15% peas were 697 cp and 523
      cp, respectively. There was a decreasing trend in degree of gelatinization with
      increase in legume incorporation level. Other RVA rheological parameters like
      trough break down and final viscosity were in the range of 266-226 cp, 431-297 cp
      and 452-375 cp respectively. Maximum values of protein, fat, fibre and ash
      contents were found in rice extrudates at 15% legumes blend levels. There was an
      increasing trend in nutrient contents with legume content in rice extrudates.
      Degree of gelatinization for rice alone extrudate was 29.4% and showed a decrease
      in gelatinization with increase in legumes extrudate and was minimum (22.4%) for
      rice blended with 15% dehulled green gram. Sensory evaluation scores for all
      extrudates showed the most acceptable range of 6 to 8. Thus, legume blend level
      (up to 15%) of dehulled legumes fetched good scores and showed promising trend
      for the production of low cost expanded extrudates and its instant flour. 

PMID- 24082278
TI  - Moisture sorption studies on vacuum dried coconut presscake.
AB  - Moisture sorption isotherms of vacuum dried coconut presscake were determined at
      25  degrees C, 30  degrees C, and 38  degrees C using a gravimetric technique.
      Sorption isotherms exhibited Type II behaviour. The effect of temperature on
      equilibrium moisture content was not significant (p > 0.05). Three models
      available in the literature viz., GAB, BET, and Halsey models were fitted to the
      sorption data. Out of the three tested models, Halsey model best fitted the
      experimental data with a relative deviation percent below 10%. The net isosteric
      heat of sorption was determined from the equilibrium adsorption data using the
      Clausius-Clapeyron equation. Isosteric heats of sorption were found to decrease
      exponentially with increasing moisture content. 

PMID- 24082279
TI  - In situ control of food spoilage fungus using Lactobacillus acidophilus NCDC 291.
AB  - A challenge for food industry today is to produce minimally processed food,
      without use of chemical preservatives and little compromise on nutritional
      status. Lactobacillus acidophilus NCDC 291 can be directly added to food where it
      enhances shelf life by competing with other microflora (both bacterial and
      fungal) for food and also by production of antimicrobial metabolites as
      bacteriocins. Comprehensive studies have demonstrated the in vitro activity of
      bacteriocins. However their role in preventing fresh food spoilage needs more
      elucidation. The present study was conducted to evaluate the efficacy of the
      whole cells of this organism as biopreservative agent against fungi. Four most
      commonly occurring spoilage fungi were isolated and were identified as Fusarium,
      Alternaria, Penicillium and Aspergillus. Growth of all of them was inhibited in
      in vitro studies, (approximately 33-43% decrease in mycelial dry weight basis
      between test and control). In situ biopreservation of Indian cheese and raw
      poultry meat was attempted and the colony count of Alternaria was significantly
      (p < 0.05, Bonferroni Holm) reduced in presence of L. acidophilus. Dip and Keep
      approach of preservation for Mangifera and Momordica were carried out in which
      microbial spoilage was not observed up to 6 days. 

PMID- 24082280
TI  - Effect of abscisic acid and hydrogen peroxide on antioxidant enzymes in Syzygium
      cumini plant.
AB  - The present study was undertaken to study the effect of abscisic acid and
      hydrogen peroxide on the activities of antioxidant enzymes namely superoxide
      dismutase (SOD; E.C. 1.15.1.1), catalase (CAT; E.C. 1.11.1.6) and ascorbate
      peroxidase (APX; E.C. 1.11.1.11) in Syzygium cumini plant. The varying
      concentrations of ABA (2-8 mM/l) and H2O2 (2-8 mM/l) modulated enzyme activities
      differently. In general, some concentrations of the ABA and H2O2 stimulated the
      activities of all the three enzymes except that there was a dose dependent
      reduction in catalase activity in the plants treated with ABA. 

PMID- 24082281
TI  - Benediction.

PMID- 24082282
TI  - The registration of medical graduates from Eastern European Union countries with
      the General Medical Council (GMC) and the Medical Council, Ireland.
AB  - The purpose of this study was to identify the number of medical graduates
      registered with the General Medical Council (GMC) between 1990 and 2005, whose
      initial training was in Eastern Europe and who came from universities which have
      subsequently developed an "English Parallel" course and are now within the
      European Union (EU). A similar exercise was undertaken with graduates registered
      with the Medical Council, Ireland. Between 1990 and 2005 one thousand six hundred
      and fourteen (1614) doctors, who had trained in the selected universities from
      Eastern Europe, registered with the General Medical Council (GMC) in the United
      Kingdom (Table 1). The Register of Medical Practitioners for Ireland as at 1st
      July 2005 was also scanned manually to identify graduates from these countries
      who were registered in Ireland. Sixty four such graduates were identified of whom
      6 qualified before 1990 and 5 were in their internship year. The study suggests
      that since 2000 younger graduates who sought training in Central and Eastern
      Europe are returning to the UK shortly after graduation to register and start
      clinical training. 

PMID- 24082283
TI  - The mediastinal staging accuracy of 18F-Fluorodeoxyglycose positron emission
      tomography/computed tomography in non-small cell lung cancer with variable time
      intervals to surgery.
AB  - BACKGROUND: PET/CT scanning can determine suitability for curative therapy and
      inform decision making when considering radical therapy in patients with non
      small cell lung cancer (NSCLC). Metastases to central mediastinal lymph nodes
      (N2) may alter such management decisions. We report a 2 year retrospective series
      assessing N2 lymph node staging accuracy with PET/CT compared to pathological
      analysis at surgery. METHODS: Patients with NSCLC attending our centre (excluding
      those who had induction chemotherapy) who had staging PET/CT scans and
      pathological nodal sampling between June 2006 and June 2008 were analysed. For
      each lymph node assessed pathologically, the corresponding PET/CT status was
      determined. 64 patients with 200 N2 lymph nodes were analysed. RESULTS:
      Sensitivity of PET/CT scans for indentifying involved N2 lymph nodes was 39%,
      specificity 96% and overall accuracy 90%. For individual lymph node analysis,
      logistic regression demonstrated a significant linear association between PET/CT
      sensitivity and time from scanning to surgery (p=0.031) but not for specificity
      and accuracy. Those scanned <9 weeks before pathological sampling were
      significantly more sensitive (64% >9 weeks, 0% >= 9 weeks, p=0.013) and more
      accurate (94% <9 weeks, 81% >= 9 weeks, p=0.007). Differences in specificity were
      not seen (97% <9 weeks, 91% >= 9 weeks, p=0.228). No significant difference in
      specificity was found at any time point. CONCLUSIONS: We recommend that if a
      PET/CT scan is older than 9 weeks, and management would be altered by the
      presence of N2 nodes, re-staging of the mediastinum should be undertaken.

PMID- 24082284
TI  - Cataract surgery planning in amblyopic patients--which eye first? Awareness of
      the potential for post-operative diplopia amongst consultant ophthalmic surgeons
      in Wales.
AB  - AIM: To explore the views of consultant ophthalmic surgeons in Wales in the
      context of planning cataract surgery in patients with amblyopia. To compare
      prevailing views and preferences with recommendations in published literature.
      METHOD: A cross-sectional survey was conducted in which all consultant
      ophthalmologists working in Wales were invited to complete an online survey
      designed using the Survey Monkey tool (http://www.surveymonkey.com). The survey
      included a clinical scenario involving an amblyopic patient with bilateral
      cataracts with questions designed to elicit responders' preferences with regard
      to which eye they would operate on first as well as the reasoning behind their
      clinical decision making. RESULTS: 32 out of 42 consultants responded to the
      survey (a response rate of >75%). With regards to the chronological order of
      surgery 18 (56.26%) indicated that they would perform cataract surgery first on
      the non-amblyopic eye, 11 (34.4%) would surgically address the amblyopic eye
      first and three (9.4%) indicated that patient preference would dictate the choice
      regarding the laterality of the eye to be operated on first. While 24 responders
      (75.0%) had encountered amblyopic patients who had developed problems after
      cataract surgery only 10 (31.3%) opined that formal guidance from the Royal
      College of Ophthalmologists was warranted. CONCLUSION: These results indicate
      that awareness of post-cataract surgery diplopia, and in particular fixation
      switch diplopia, is not widespread amongst consultant ophthalmic surgeons in
      Wales.

PMID- 24082285
TI  - Outcome of 131I therapy in hyperthyroidism using a 550MBq fixed dose regimen.
AB  - BACKGROUND: Radioiodine is the treatment of choice for relapsed hyperthyroidism
      although the optimum protocol is uncertain. Fixed dose radioiodine is
      increasingly popular but responses may vary. AIM: To assess the outcome of 131I
      therapy in hyperthyroidism using a standard dose regimen in a regional referral
      centre and to explore factors influencing outcome. METHODS: We studied 449
      patients (M:F 82:367; age range 13-89 y, median 42 y) with hyperthyroidism
      treated between 2003 and 2007 with a standard dose of 550 MBq 131I. Patients were
      classified as either Graves' disease, toxic multinodular goitre or indeterminate
      aetiology. Antithyroid drugs were routinely stopped at least 1 week before
      radioiodine. RESULTS: One year after radioiodine 334 (74%) were hypothyroid, 85
      (19%) were euthyroid and 30 (7%) had required a further dose of 131I. Patients
      with Graves' disease were more likely to become hypothyroid than those with toxic
      multinodular goitre (78% v 37%, p<0.001) and less likely to become euthyroid (11%
      v 55%, p<0.001). Free T4 >80 pmol/L (normal range 9.0 - 19.0 pmol/L) at
      presentation was associated with an increased failure rate (17% compared with 5%
      and 3% for 40-79 pmol/L and <40 pmol/L respectively; p=0.01). Patients with
      either a small or no goitre were more likely to be successfully treated by a
      single dose (96%) than those with a medium/large goitre (85%, p<0.001). Anti
      thyroid medication was taken by 345 (77%) (carbimazole n=319) patients up to 1
      week prior to 131I and was associated with an increased failure rate (8% v 2%,
      p=0.027) compared to those who had not had antithyroid medication. Logistic
      regression showed free T4 at presentation to be the only independent risk factor
      for failure of the first dose of radioiodine (OR 2.5; 95% CI, 1.2-5.1, p=0.012).
      CONCLUSION: A single standard dose of 550 MBq 131I is highly effective in
      treating hyperthyroidism. The aetiology, severity of hyperthyroidism at
      diagnosis, goitre size and prior antithyroid medication all had a significant
      effect on outcome.

PMID- 24082286
TI  - Recombinant PTH: a study of the outcome of teriparatide therapy for 138 patients
      with osteoporosis.
AB  - INTRODUCTION: Osteoporosis results in significant morbidity and mortality for a
      large number of patients within Northern Ireland. Recombinant PTH (Teriparatide)
      is one of a growing number of treatment options for the disease. METHODS: A
      retrospective analysis was carried out for all patients who had been commenced on
      Teriparatide since it was first used in the Belfast Health and Social Care Trust
      (BHSCT) in 2007. Patient demographics, clinical history and prior treatment were
      recorded prior to an eighteen month treatment protocol. Outcome measures
      including bone densitometry, bone turnover markers and health status were
      assessed on commencement and completion. RESULTS: 138 patients have commenced
      teriparatide therapy since 2007 (9 male, 129 female). At the time of analysis 60
      patients had completed treatment, 53 patients were receiving ongoing treatment
      and 25 patients did not complete the 18 month course. On completion vertebral
      bone mineral density (BMD) had increased by 8.3% while femoral neck BMD had
      increased by 3.5%. Bone turnover markers demonstrated a significant increase of
      bone formation and resorption at 4 months, with a smaller increase at 18 months.
      Health outcome measures (EuroQoL-5 and patient visual analogue scale) indicated
      improvement in the quality of life of patients of those who completed the
      treatment course. CONCLUSIONS: Experience in the BHSCT with teriparatide since
      2007 demonstrates improvement in BMD comparable to published data, changes in
      bone turnover markers consistent with increased bone remodeling and better health
      outcomes for patients.

PMID- 24082287
TI  - Tracheal bronchus associated with recurrent pneumonia.
AB  - Abnormalities of the major airways are very uncommon congenital conditions which
      occur in approximately 2% of the adult population. Usually aberrant bronchi are
      asymptomatic and are only found by coincidence. We present the rare case of a 49
      years-old woman with a tracheal bronchus causing associated with recurrent
      pneumonia of the right upper lobe. 

PMID- 24082288
TI  - Chemotherapy causes cancer! A case report of therapy related acute myeloid
      leukaemia in early stage breast cancer.
AB  - Use of chemotherapy and radiotherapy in the adjuvant setting has improved
      survival for many patients with malignancy. Unfortunately multimodality treatment
      can come at a price, in particular therapy-related malignancies. This has
      importance in that patients must be made aware of this potential detriment from
      therapy and doctors must consider this diagnosis in those patients who are cancer
      survivors and presenting with health problems. We present a case report and brief
      overview of the literature regarding chemotherapy-induced acute myeloid leukaemia
      (AML) following therapy for early stage breast cancer. 

PMID- 24082289
TI  - Imaging in cauda equina syndrome--a pictorial review.

PMID- 24082290
TI  - Thinking otherwise: Royal Victoria Hospital, Wednesday 26th September 2012.

PMID- 24082291
TI  - Our blood your money.

PMID- 24082292
TI  - Increasingly hard to swallow--18 years of changing tonsillectomy practice in
      Northern Ireland.

PMID- 24082293
TI  - So you want to be a medical student in Europe?

PMID- 24082296
TI  - Here come the sleep apnea-cancer studies.

PMID- 24082297
TI  - Astrocytes do the "shuttle".

PMID- 24082298
TI  - Let the vessels rest.

PMID- 24082299
TI  - Another advance in oral appliance therapy?

PMID- 24082300
TI  - Evaluating behavioral weight loss programs for sleep apnea.

PMID- 24082301
TI  - Sleep duration and chronic diseases among U.S. adults age 45 years and older:
      evidence from the 2010 Behavioral Risk Factor Surveillance System.
AB  - STUDY OBJECTIVE: To examine the effects of obesity and frequent mental distress
      (FMD) on the relationship of sleep duration with coronary heart disease (CHD),
      stroke, and diabetes. DESIGN: Cross-sectional study. SETTING: Population-based
      surveillance. PARTICIPANTS: There were 54,269 adults age 45 y or older who
      completed the 2010 Behavioral Risk Factor Surveillance System survey in 14
      states. RESULTS: Nearly one third (31.1% or an estimated 11.1 million) of
      respondents age 45 y and older reported being short sleepers (<= 6 h), 64.8%
      being optimal sleepers (7-9 h), and 4.1% being long sleepers (>= 10 h) in a 24-h
      period. Compared with the optimal sleep duration, both short and long sleep
      durations were significantly associated with obesity, FMD (mental health was not
      good >= 14 days during the past 30 days), CHD, stroke, and diabetes after
      controlling for sex, age, race/ethnicity, and education. The U-shaped
      relationships of sleep duration with CHD, stroke, and diabetes were moderately
      attenuated by FMD. The relationship between sleep duration and diabetes was
      slightly attenuated by obesity. CONCLUSIONS: Sleep duration had U-shaped
      relationships with leading chronic diseases. Further prospective studies are
      needed to determine how mental health and maintenance of a normal weight may
      interact with sleep duration to prevent chronic diseases.

PMID- 24082302
TI  - Symptoms of sleep disordered breathing and risk of cancer: a prospective cohort
      study.
AB  - STUDY OBJECTIVES: Sleep disordered breathing (SDB) has been associated with
      oxidative stress, inflammation, and altered hormonal levels, all of which could
      affect the risk of cancer. The aim of the study is to examine if symptoms of SDB
      including snoring, breathing cessations, and daytime sleepiness affect the
      incidence of total cancer and subtypes of cancer. DESIGN: Prospective cohort
      study. SETTING: The third wave (1991-1993) of the Copenhagen City Heart Study.
      PARTICIPANTS: There were 8,783 men and women in whom cancer had not been
      previously diagnosed. MEASUREMENTS AND RESULTS: Participants answered questions
      about snoring and breathing cessations in 1991-1993, whereas information about
      daytime sleepiness based on the Epworth Sleepiness Scale was collected in a
      subset of the participants (n = 5,894) in 1998. First-time incidence of cancer
      was followed until December 2009 in a nationwide cancer register. We found no
      overall association between symptoms of SDB and incident cancer. Yet, in the
      small group with high daytime sleepiness, we observed a surprisingly higher
      cancer incidence (hazard ratio = 4.09; 95% CI 1.58-10.55) in persons younger than
      50 years. We also found a higher risk of virus/immune-related cancers (2.73; 1.27
      5.91) and alcohol-related cancers (4.92; 1.45-16.76) among persons with daytime
      sleepiness. More SDB symptoms were associated with a higher risk of smoking
      related cancers (Ptrend: 0.04). Apart from these findings there were no clear
      associations between symptoms of sleep disordered breathing and cancer subtypes.
      CONCLUSION: We found very limited evidence of relationship between symptoms of
      sleep disordered breathing and incidence of cancer.

PMID- 24082303
TI  - Association between sleep and breast cancer incidence among postmenopausal women
      in the Women's Health Initiative.
AB  - STUDY OBJECTIVES: To determine whether the duration of sleep, sleep quality,
      insomnia, or sleep disturbance was associated with incident breast cancer in the
      Women's Health Initiative (WHI). DESIGN: Prospective cohort study. SETTING: Women
      enrolled in one of the Clinical Trial (CT) arms or the Observational Study (OS)
      from the WHI conducted in the United States. PARTICIPANTS: This study included
      110,011 women age 50 to 79 years with no history of cancer. MEASUREMENTS AND
      RESULTS: Typical sleep duration, sleep quality, and other self-reported sleep
      measures over the past 4 weeks were assessed during the screening visits for both
      the CT and OS participants. The presence of insomnia and level of sleep
      disturbance was calculated from an index of the WHI Insomnia Rating Scale. The
      outcome for this study was primary, invasive breast cancer. A total of 5,149
      incident cases of breast cancer were identified in this study. No statistically
      significant associations were found between sleep duration, sleep quality,
      insomnia, or level of sleep disturbance with the risk of breast cancer after
      multivariable adjustment. A positive trend was observed for increasing sleeping
      duration with the risk of estrogen receptor positive breast cancer, but the
      association estimates for each sleep duration category were weak and
      nonsignificant. CONCLUSIONS: This study does not provide strong support for an
      association between self-reported sleep duration, sleep quality, insomnia, or
      sleep disturbance with the risk of breast cancer.

PMID- 24082304
TI  - Genes involved in the astrocyte-neuron lactate shuttle (ANLS) are specifically
      regulated in cortical astrocytes following sleep deprivation in mice.
AB  - STUDY OBJECTIVES: There is growing evidence indicating that in order to meet the
      neuronal energy demands, astrocytes provide lactate as an energy substrate for
      neurons through a mechanism called "astrocyte-neuron lactate shuttle" (ANLS).
      Since neuronal activity changes dramatically during vigilance states, we
      hypothesized that the ANLS may be regulated during the sleep-wake cycle. To test
      this hypothesis we investigated the expression of genes associated with the ANLS
      specifically in astrocytes following sleep deprivation. Astrocytes were purified
      by fluorescence-activated cell sorting from transgenic mice expressing the green
      fluorescent protein (GFP) under the control of the human astrocytic GFAP
      promoter. DESIGN: 6-hour instrumental sleep deprivation (TSD). SETTING: Animal
      sleep research laboratory. PARTICIPANTS: Young (P23-P27) FVB/N-Tg (GFAP-GFP)
      14Mes/J (Tg) mice of both sexes and 7-8 week male Tg and FVB/Nj mice.
      INTERVENTIONS: Basal sleep recordings and sleep deprivation achieved using a
      modified cage where animals were gently forced to move. MEASUREMENTS AND RESULTS:
      Since Tg and FVB/Nj mice displayed a similar sleep-wake pattern, we performed a
      TSD in young Tg mice. Total RNA was extracted from the GFP-positive and GFP
      negative cells sorted from cerebral cortex. Quantitative RT-PCR analysis showed
      that levels of Glut1, alpha-2-Na/K pump, Glt1, and Ldha mRNAs were significantly
      increased following TSD in GFP-positive cells. In GFP-negative cells, a tendency
      to increase, although not significant, was observed for Ldha, Mct2, and alpha-3
      Na/K pump mRNAs. CONCLUSIONS: This study shows that TSD induces the expression of
      genes associated with ANLS specifically in astrocytes, underlying the important
      role of astrocytes in the maintenance of the neuro-metabolic coupling across the
      sleep-wake cycle.

PMID- 24082305
TI  - Vascular compliance limits during sleep deprivation and recovery sleep.
AB  - STUDY OBJECTIVES: Our previous studies showed that evoked hemodynamic responses
      are smaller during wake compared to sleep; suggesting neural activity is
      associated with vascular expansion and decreased compliance. We explored whether
      prolonged activity during sleep deprivation may exacerbate vascular expansion and
      blunt hemodynamic responses. DESIGN: Evoked auditory responses were generated
      with periodic 65 dB speaker clicks over a 72-h period and measured with cortical
      electrodes. Evoked hemodynamic responses were measured simultaneously with
      optical techniques using three light-emitting diodes, and a photodiode. SETTING:
      Animals were housed in separate 30*30*80 cm enclosures, tethered to a commutator
      system and maintained on a 12-h light/dark cycle. Food and water were available
      ad libitum. PATIENTS OR PARTICIPANTS: Seven adult female Sprague-Dawley rats.
      INTERVENTIONS: Following a 24-h baseline recording, sleep deprivation was
      initiated for 0 to 10 h by gentle handling, followed by a 24-h recovery sleep
      recording. Evoked electrical and hemodynamic responses were measured before,
      during, and after sleep deprivation. MEASUREMENTS AND RESULTS: Following
      deprivation, evoked hemodynamic amplitudes were blunted. Steady-state
      oxyhemoglobin concentration increased during deprivation and remained high during
      the initial recovery period before returning to baseline levels after
      approximately 9-h. CONCLUSIONS: Sleep deprivation resulted in blood vessel
      expansion and decreased compliance while lower basal neural activity during
      recovery sleep may allow blood vessel compliance to recover. Chronic sleep
      restriction or sleep deprivation could push the vasculature to critical levels,
      limiting blood delivery, and leading to metabolic deficits with the potential for
      neural trauma.

PMID- 24082306
TI  - Long-term intermittent hypoxia elevates cobalt levels in the brain and injures
      white matter in adult mice.
AB  - STUDY OBJECTIVES: Exposure to the variable oxygenation patterns in obstructive
      sleep apnea (OSA) causes oxidative stress within the brain. We hypothesized that
      this stress is associated with increased levels of redox-active metals and white
      matter injury. DESIGN: Participants were randomly allocated to a control or
      experimental group (single independent variable). SETTING: University animal
      house. PARTICIPANTS: Adult male C57BL/6J mice. INTERVENTIONS: To model OSA, mice
      were exposed to long-term intermittent hypoxia (LTIH) for 10 hours/day for 8
      weeks or sham intermittent hypoxia (SIH). MEASUREMENTS AND RESULTS: Laser
      ablation-inductively coupled plasma-mass spectrometry was used to quantitatively
      map the distribution of the trace elements cobalt, copper, iron, and zinc in
      forebrain sections. Control mice contained 62 +/- 7 ng cobalt/g wet weight,
      whereas LTIH mice contained 5600 +/- 600 ng cobalt/g wet weight (P < 0.0001).
      Other elements were unchanged between conditions. Cobalt was concentrated within
      white matter regions of the brain, including the corpus callosum. Compared to
      that of control mice, the corpus callosum of LTIH mice had significantly more
      endoplasmic reticulum stress, fewer myelin-associated proteins, disorganized
      myelin sheaths, and more degenerated axon profiles. Because cobalt is an
      essential component of vitamin B12, serum methylmalonic acid (MMA) levels were
      measured. LTIH mice had low MMA levels (P < 0.0001), indicative of increased B12
      activity. CONCLUSIONS: Long-term intermittent hypoxia increases brain cobalt,
      predominantly in the white matter. The increased cobalt is associated with
      endoplasmic reticulum stress, myelin loss, and axonal injury. Low plasma
      methylmalonic acid levels are associated with white matter injury in long-term
      intermittent hypoxia and possibly in obstructive sleep apnea.

PMID- 24082307
TI  - Intermittent hypoxia impairs glucose homeostasis in C57BL6/J mice: partial
      improvement with cessation of the exposure.
AB  - OBJECTIVES: Obstructive sleep apnea is associated with insulin resistance,
      glucose intolerance, and type 2 diabetes mellitus. Although several studies have
      suggested that intermittent hypoxia in obstructive sleep apnea may induce
      abnormalities in glucose homeostasis, it remains to be determined whether these
      abnormalities improve after discontinuation of the exposure. The objective of
      this study was to delineate the effects of intermittent hypoxia on glucose
      homeostasis, beta cell function, and liver glucose metabolism and to investigate
      whether the impairments improve after the hypoxic exposure is discontinued.
      INTERVENTIONS: C57BL6/J mice were exposed to 14 days of intermittent hypoxia, 14
      days of intermittent air, or 7 days of intermittent hypoxia followed by 7 days of
      intermittent air (recovery paradigm). Glucose and insulin tolerance tests were
      performed to estimate whole-body insulin sensitivity and calculate measures of
      beta cell function. Oxidative stress in pancreatic tissue and glucose output from
      isolated hepatocytes were also assessed. RESULTS: Intermittent hypoxia increased
      fasting glucose levels and worsened glucose tolerance by 67% and 27%,
      respectively. Furthermore, intermittent hypoxia exposure was associated with
      impairments in insulin sensitivity and beta cell function, an increase in liver
      glycogen, higher hepatocyte glucose output, and an increase in oxidative stress
      in the pancreas. While fasting glucose levels and hepatic glucose output
      normalized after discontinuation of the hypoxic exposure, glucose intolerance,
      insulin resistance, and impairments in beta cell function persisted. CONCLUSIONS:
      Intermittent hypoxia induces insulin resistance, impairs beta cell function,
      enhances hepatocyte glucose output, and increases oxidative stress in the
      pancreas. Cessation of the hypoxic exposure does not fully reverse the observed
      changes in glucose metabolism.

PMID- 24082308
TI  - What are you looking at? Moving toward an attentional timeline in insomnia: a
      novel semantic eye tracking study.
AB  - STUDY OBJECTIVES: To date, cognitive probe paradigms have been used in different
      guises to obtain reaction time measurements suggestive of an attention bias
      towards sleep in insomnia. This study adopts a methodology which is novel to
      sleep research to obtain a continual record of where the eyes-and therefore
      attention-are being allocated with regard to sleep and neutral stimuli. DESIGN: A
      head mounted eye tracker (Eyelink II,SR Research, Ontario, Canada) was used to
      monitor eye movements in respect to two words presented on a computer screen,
      with one word being a sleep positive, sleep negative, or neutral word above or
      below a second distracter pseudoword. Probability and reaction times were the
      outcome measures. PARTICIPANTS: Sleep group classification was determined by
      screening interview and PSQI (> 8 = insomnia, < 3 = good sleeper) score.
      MEASUREMENTS AND RESULTS: Those individuals with insomnia took longer to fixate
      on the target word and remained fixated for less time than the good sleep
      controls. Word saliency had an effect with longer first fixations on positive and
      negative sleep words in both sleep groups, with largest effect sizes seen with
      the insomnia group. CONCLUSIONS: This overall delay in those with insomnia with
      regard to vigilance and maintaining attention on the target words moves away from
      previous attention bias work showing a bias towards sleep, particularly negative,
      stimuli but is suggestive of a neurocognitive deficit in line with recent
      research.

PMID- 24082309
TI  - Decision-making, reward-seeking behaviors and dopamine agonist therapy in
      restless legs syndrome.
AB  - STUDY OBJECTIVES: To assess whether the frequency of impulse control disorders
      (ICDs), addictive behaviors, impulsivity, and impairment of decision-making task
      performance under ambiguous and risky conditions were present in patients with
      restless legs syndrome (RLS) and whether changes could be related to dopaminergic
      medications. DESIGN: Case-control prospective study. SETTING: Academic Sleep
      Disorders Center. PARTICIPANTS: Of the 149 participants, there were 39 who were
      drug free with primary RLS, 50 who were taking dopamine agonists (DA), and 60
      control subjects. Participants were assessed with a clinical interview screening
      for ICDs, augmentation syndrome, impulsivity, depression, and addictive
      behaviors. All participants completed two decision-making tasks, one under an
      ambiguous condition (Iowa Gambling Task) and the other under a risky condition
      (Game of Dice Task). Drug-free patients with RLS underwent 1 night of
      polysomnography recording. MEASUREMENTS AND RESULTS: Seventy percent of patients
      were treated with pramipexole (median dose, 0.36 mg), and 30% with ropinirole
      (median dose, 0.75 mg). Median duration of DA intake was 11 mo (range, 1-72 mo).
      No differences were found on impulsivity scores, ICDs, and substance addiction
      between drug-free patients or those taking DA, or control subjects. Patients with
      RLS reported more depressive symptoms than control subjects, but without
      differences between patients taking or not taking DA. Drug-free and treated
      patients demonstrated reduced performances on the Iowa Gambling Task but not on
      the Game of Dice Task compared to control subjects, with no differences between
      patients taking medications and those who were not. No association was found
      between decision-making task performances, or polysomnographic and clinical
      variables. CONCLUSION: Impulse control disorders, impulsivity, and substance
      addiction were infrequent in drug-free patients with restless legs syndrome or
      those treated with a low dose of dopamine agonists. However, patients with
      restless legs syndrome, either drug free or taking dopamine agonists, had
      preferences toward risky choices on the Iowa Gambling Task, which led to negative
      consequences in the long run, a condition potentially leading to further
      development of impulse control disorders.

PMID- 24082310
TI  - Obstructive sleep apnea is associated with preserved bone mineral density in
      healthy elderly subjects.
AB  - STUDY OBJECTIVES: Chronic intermittent hypoxia (IH) acts as a stimulator of
      mesenchymal stem cell (MSC) mobilization, intensifying osteoblast formation in
      animal models. The recurrence of apnea and oxygen desaturation in obstructive
      sleep apnea (OSA) may mimic experimental models of IH. We hypothesized that in
      elderly with OSA, apnea-related IH may mobilize MSCs and thereby prevent the age
      related decline in osteogenesis. This study explored the relationship between OSA
      and bone mineral density (BMD), and the effect of IH on BMD, in a large sample of
      elderly subjects. PARTICIPANTS: There were 833 volunteers age 68.6 +/- 0.8 y (59%
      women). INTERVENTION: Each participant underwent evaluation of BMD at lumbar
      spine and femoral sites by dual-energy x-ray absorptiometry (DEXA) as well as
      clinical and polygraphic examinations. OSA was diagnosed on the basis of an apnea
      hypopnea index (AHI) >= 15. MEASUREMENTS AND RESULTS: There were 55% of the
      participants who presented with OSA, and these subjects were predominantly male
      and overweight. Compared with subjects without OSA, those with OSA had a higher
      femoral and spinal BMD (P < 0.001). Body mass index (BMI), AHI, and oxygen
      desaturation index (ODI) (P < 0.01) were significantly related to BMD. After
      adjustment for sex, BMI, metabolic values, and hypertension, multiple regression
      analysis showed a significant association between femoral and lumbar T scores and
      both daily energy expenditure (P < 0.001) and ODI (P = 0.007). CONCLUSIONS: In
      elderly subjects, the presence of obstructive sleep apnea is associated with
      higher bone mineral density, with oxygen desaturation index being a significant
      determinant of bone metabolism. These results suggest that apnea-related
      intermittent hypoxia may stimulate the bone remodeling process in older
      population. CLINICAL TRIAL REGISTRATION: NCT 00759304 and NCT 00766584.

PMID- 24082311
TI  - Remotely controlled mandibular protrusion during sleep predicts therapeutic
      success with oral appliances in patients with obstructive sleep apnea.
AB  - STUDY OBJECTIVES: The present study addresses the need for a validated tool that
      prospectively identifies favorable candidates for oral appliance therapy in
      treatment of obstructive sleep apnea. The objective of the study was to evaluate
      the ability of a mandibular titration study, performed with a remotely controlled
      mandibular positioner (RCMP), to predict treatment outcome with a mandibular
      repositioning appliance (MRA) and to predict an effective target protrusive
      position (ETPP). DESIGN: A prospective, blinded, outcome study. SETTING: Standard
      clinical care with tests performed in the polysomnographic laboratory.
      PARTICIPANTS: Consecutive patients (n = 67) recruited from a sleep center or a
      dental practice using broad inclusion criteria (age 21-80 years; AHI > 10/h; BMI
      < 40 kg/m(2)). INTERVENTIONS: Therapeutic outcome with a mandibular protruding
      oral appliance was predicted following a mandibular protrusive titration study in
      the polysomnographic laboratory using a remotely controlled positioner and
      prospectively established predictive rules. An ETPP was also prospectively
      determined for participants predicted to be therapeutically successful with MRA
      therapy. All participants were blindly treated with a MRA, at either the
      predicted ETPP or a sham position, and therapeutic outcome was compared against
      prediction. MEASUREMENTS AND RESULTS: At the final protrusive position, standard
      predictive parameters (sensitivity, specificity, positive and negative predictive
      values) showed statistically significant predictive accuracy (P < 0.05) in the
      range of 83% to 94%. The predicted ETPP provided an efficacious protrusive
      position in 87% of participants predicted to be therapeutically successful with
      MRA therapy (P < 0.05). CONCLUSIONS: Using prospectively established rules for
      interpreting the polysomnographic data, the mandibular titration study predicted
      mandibular repositioning appliance therapeutic outcome with significant accuracy,
      particularly with regard to accurately predicting therapeutic success. As well,
      among the participants predicted to be therapeutically successful with mandibular
      repositioning appliance therapy, the effective target protrusive position
      provided efficacious mandibular protrusion in the majority.

PMID- 24082312
TI  - Cognitive performances and mild cognitive impairment in idiopathic rapid eye
      movement sleep behavior disorder: results of a longitudinal follow-up study.
AB  - STUDY OBJECTIVES: To investigate the capacity of neuropsychological deficits in
      idiopathic rapid eye movement sleep behavior disorder (iRBD) to predict the
      development of dementia and/or parkinsonism. DESIGN: Prospective longitudinal
      follow-up study. SETTING: Tertiary sleep center. PATIENTS: Twenty patients with
      initial iRBD (19 males, mean age 66.1 +/- 7.1) underwent a clinical and
      neuropsychological follow-up within a mean of 43 +/- 19 months.
      Neuropsychological performances at baseline were compared with those of healthy
      controls matched for sex, age, and education. INTERVENTIONS: Discontinuation of
      clonazepam at least 7 days before the follow-up evaluation. RESULTS: At follow
      up, the Wilcoxon test showed a significant worsening of scores on Raven Colored
      Matrices 47 (P = 0.01), Attentive matrices (P = 0.002), phonemic (P = 0.04) and
      sematic (P = 0.04) fluency. Thirteen patients (65%) showed cognitive
      deterioration involving multiple domains. Of these, four patients (20%)
      maintained a stable cognitive dysfunction and nine (45%) showed a progression of
      cognitive dysfunction: six (30%) in constructional abilities (P = 0.03), four
      (20%) in short-term memory (P = NS), three (15%) in executive functions and non
      verbal logic (P = NS), one (5%) in verbal fluency (P = NS), and one (5%) in long
      term memory (P = NS) (McNemar test). Seven patients (35%) retained a normal
      cognitive profile. Mild cognitive impairment (MCI) was diagnosed at baseline in
      seven patients (35%). At follow-up, three of these patients showed overt dementia
      that was accompanied by parkinsonism in all cases; one had worsened from non
      amnesic single-domain to nonamnesic multiple-domain MCI, two were stable, and one
      patient no longer met the criteria for MCI. Four patients (20%) without MCI at
      baseline had MCI at follow-up. Patients who developed MCI/dementia had an older
      age at disease onset (65.8 +/- 5.4 versus 56.8 +/- 9.3; P = 0.01) compared with
      those who did not. CONCLUSIONS: Our findings corroborate evidence that
      visuospatial abilities constitute the area most affected in idiopathic rapid eye
      movement sleep behavior disorder (learning as a stable deficit and copying as an
      evolving deficit). Cognitive deterioration, involving mainly nonverbal logic,
      attention, and executive functions, can be observed in rapid eye movement sleep
      behavior disorder follow-up, suggesting an underlying evolving degenerative
      process. Our data confirm that mild cognitive impairment is frequent in
      idiopathic rapid eye movement sleep behavior disorder. The presence of mild
      cognitive impairment predicts the eventual risk of developing dementia, which
      seemed to be associated with parkinsonism.

PMID- 24082313
TI  - Midlife sleep characteristics associated with late life cognitive function.
AB  - STUDY OBJECTIVES: Previous studies with limited follow-up times have suggested
      that sleep-related traits are associated with an increased risk of incident
      dementia or cognitive decline. We investigated the association between midlife
      sleep characteristics and late life cognitive function. DESIGN: A follow-up study
      with a median follow-up time of 22.5 (range 15.8-25.7) years assessing the
      association between midlife sleep characteristics and later cognitive function.
      SETTING: Questionnaire data from 1981 were used in the assessment of sleep
      characteristics, use of hypnotics, and covariates at baseline. Between 1999 and
      2007, participants were assigned a linear cognitive score with a maximum score of
      51 based on a telephone interview (mean score 38.3, SD 6.1). Linear regression
      analyses were controlled for age, sex, education, ApoE genotype, and follow-up
      time. PARTICIPANTS: 2,336 members of the Finnish Twin cohort who were at least 65
      years of age. INTERVENTIONS: N/A. MEASUREMENTS AND RESULTS: Baseline short (< 7
      h/day) and long (> 8 h/day) sleepers had lower cognitive scores than participants
      sleeping 7-8 h/ day (beta = -0.84, P = 0.014 and beta = -1.66, P < 0.001,
      respectively). As compared to good sleep quality, poor or rather poor sleep
      quality was associated with a lower cognitive score (beta = -1.00, P = 0.011).
      Also, the use of hypnotics >= 60 days per year was associated with poorer
      cognitive function (beta = -1.92, P = 0.002). CONCLUSIONS: This is the first
      study indicating that midlife sleep length, sleep quality, and use of hypnotics
      are associated with late life cognitive function. Further confirmation is needed,
      but sleep-related characteristics may emerge as new risk factors for cognitive
      impairment.

PMID- 24082314
TI  - Associations of neighborhood characteristics with sleep timing and quality: the
      Multi-Ethnic Study Of Atherosclerosis.
AB  - STUDY OBJECTIVES: To investigate the associations of specific neighborhood
      features (disorder, safety, social cohesion, physical environment, and
      socioeconomic status) with sleep duration and quality. DESIGN: Cross-sectional.
      One wave of a population-based study (Multi-Ethnic Study of Atherosclerosis).
      SETTING: Community-dwelling participants in New York, NY and Los Angeles, CA.
      PARTICIPANTS: There were 1,406 participants (636 males, 770 females).
      INTERVENTIONS: NA. MEASUREMENTS AND RESULTS: Sleep was assessed using reported
      hours of sleep, the Epworth Sleepiness Scale, and insomnia symptoms. Neighborhood
      characteristics were assessed via questionnaires administered to neighbors of
      study participants and were aggregated to the neighborhood (census tract) level
      using empirical Bayes estimation. An adverse social environment (characterized by
      high disorder, and low safety and social cohesion) was associated with shorter
      sleep duration after adjustment for the physical environment, neighborhood and
      individual-level socioeconomic status (SES), and other short sleep risk factors
      (mean difference per standard deviation increase in summary social environment
      scale 0.24 h 95% confidence interval 0.08, 0.43). Adverse neighborhood social and
      physical environments, and neighborhood SES were associated with greater
      sleepiness, but associations with physical environments were no longer
      statistically significant after adjustment for sociodemographic characteristics.
      Neighborhood SES was a weaker and less consistent predictor of specific measures
      of neighborhood social and physical environments. Neighborhood characteristics
      were not associated with insomnia. CONCLUSIONS: Shortened sleep related to
      adverse social environments represents one potential pathway through which
      neighborhoods may influence health.

PMID- 24082315
TI  - Effectiveness of lifestyle interventions on obstructive sleep apnea (OSA):
      systematic review and meta-analysis.
AB  - BACKGROUND: Obstructive sleep apnea (OSA) is a common sleep disorder associated
      with several adverse health outcomes. Given the close association between OSA and
      obesity, lifestyle and dietary interventions are commonly recommended to
      patients, but the evidence for their impact on OSA has not been systematically
      examined. OBJECTIVES: To conduct a systematic review and meta-analysis to assess
      the impact of weight loss through diet and physical activity on measures of OSA:
      apnea-hypopnea index (AHI) and oxygen desaturation index of 4% (ODI4). METHODS: A
      systematic search was performed to identify publications using Medline (1948-2011
      week 40), EMBASE (from 1988-2011 week 40), and CINAHL (from 1982-2011 week 40).
      The inverse variance method was used to weight studies and the random effects
      model was used to analyze data. RESULTS: Seven randomized controlled trials (519
      participants) showed that weight reduction programs were associated with a
      decrease in AHI (-6.04 events/h [95% confidence interval -11.18, -0.90]) with
      substantial heterogeneity between studies (I(2) = 86%). Nine uncontrolled before
      after studies (250 participants) showed a significant decrease in AHI (-12.26
      events/h [95% confidence interval -18.51, -6.02]). Four uncontrolled before-after
      studies (97 participants) with ODI4 as outcome also showed a significant decrease
      in ODI4 (-18.91 episodes/h [95% confidence interval -23.40, -14.43]).
      CONCLUSIONS: Published evidence suggests that weight loss through lifestyle and
      dietary interventions results in improvements in obstructive sleep apnea
      parameters, but is insufficient to normalize them. The changes in obstructive
      sleep apnea parameters could, however, be clinically relevant in some patients by
      reducing obstructive sleep apnea severity. These promising preliminary results
      need confirmation through larger randomized studies including more intensive
      weight loss approaches.

PMID- 24082316
TI  - Association between total sleep duration and suicidal ideation among the Korean
      general adult population.
AB  - STUDY OBJECTIVES: Examine the association between sleep duration and suicidal
      ideation in Korean adults. DESIGN: Cross-sectional survey. SETTING: Data obtained
      by the Korea National Health and Nutrition Examination Survey IV (2007-2009)
      using a rolling sampling design involving a complex, stratified, multistage, and
      probability-cluster survey of civilian non-institutionalized Korean residents.
      PARTICIPANTS: A total of 15,236 subjects (6,638 males and 8,598 females) >= 19
      years old. MEASUREMENTS AND RESULTS: The weighted prevalence of self-reported
      short sleep duration (<= 5 h/day) was 11.7% in males and 15% in females, and of
      long sleep duration (>= 9 h/day) was 6.7% in males and 8.9% in females. A U
      shaped relationship existed, with both short and long sleep durations associated
      with a higher suicidal ideation risk. Multiple logistic regression analysis was
      used to analyze the relationship between sleep duration and suicidal ideation,
      adjusting for sociodemographic factors, health behavior, and health status. After
      controlling for covariates, people with short sleep were 38.1% more likely to
      have suicidal ideation (OR = 1.381, 95% CI 1.156-1.650) than people with sleep
      duration of 7 h/day. Suicidal ideation was 1.196 times higher (95% CI: 0.950
      1.507) in long-sleeping people than people sleeping 7 h/day, although
      statistically not significant. Inclusion of depressive mood (a potential
      confounder) in multiple logistic regression models attenuated but did not
      eliminate the sleep duration/suicidal ideation association. LIMITATIONS: Sleep
      duration and suicidal ideation were assessed only by self-report. CONCLUSIONS:
      The sleep duration/suicidal ideation relationship is U-shaped in the Korean adult
      population. Self-reported habitual sleep duration may be a useful behavioral
      indicator for both individual and societal suicidal ideation risk.

PMID- 24082318
TI  - Ethnoveterinary application of Morinda citrifolia fruit puree on a commercial
      heifer rearing facility with endemic salmonellosis.
AB  - We have previously reported that Morinda citrifolia (noni) puree modulates
      neonatal calves developmental maturation of the innate and adaptive immune
      system. In this study, the effect of noni puree on respiratory and
      gastrointestinal (GI), health in preweaned dairy calves on a farm with endemic
      salmonellosis was examined. Two clinical trials were conducted whereby each trial
      evaluated one processing technique of noni puree. Trials 1 and 2 tested noni
      versions A and B, respectively. Puree analysis and trial methods were identical
      to each other, with the calf as the experimental unit. Calves were designated to
      1 of 3 treatment groups in each trial and received either: 0, 15 or 30 mL every
      12 hr of noni supplement for the first 3 weeks of life. Health scores, weaning
      age, weight gain from admission to weaning, and weaned by 6 weeks, were used as
      clinical endpoints for statistical analysis. In trial 1, calves supplemented with
      15 mL noni puree of version A every 12 hr had a higher probability of being
      weaned by 6 weeks of age than control calves (P = 0.04). In trial 2, calves
      receiving 30 mL of version B every 12 hr had a 54.5% reduction in total medical
      treatments by 42 days of age when compared to controls (P = 0.02). There was a
      trend in reduced respiratory (61%), and GI (52%) medical treatments per calf when
      compared to controls (P = 0.06 and 0.08, respectively). There were no differences
      in weight gain or mortality for any treatment group in either trial. 

PMID- 24082319
TI  - Effects of a Chinese medicinal plant Radix astragali on the ovariectomized female
      rats.
AB  - Perimenopausal syndrome occurs during the transition to menopause. Complementary
      and alternative medicine, especially Chinese medicinal plants, has manifested
      significant effects in alleviating perimenopausal symptoms. However, little
      research has been focused on the effects of Chinese medicinal plant on the immune
      function of the perimenopausal women. The present study aimed to explore the
      effects of Radix Astragali (RA) on the sex hormone levels and the interleukins of
      the ovariectomized female rats. 24 female Sprague-Dawley (SD) rats were randomly
      divided into model control group (MOD group), sham-operation group (SHAM group),
      RA group and estrogen group (EST group). After all the treatment ended, the serum
      levels of estradiol (E2), follicle stimulating hormone (FSH), luteinizing hormone
      (LH), interleukin-2 (IL-2), and interleukin-8 (IL-8) were measured using enzyme
      linked immune-sorbent assay (ELISA) and the uterus was removed and weighed after
      blood exsanguinations immediately. In the MOD group, the serum levels of E2 were
      significantly lower, and the serum levels of FSH and LH were markedly higher than
      those of the RA group, EST group and SHAM group (P<0.05). In the RA group, the
      serum levels of E2 were significantly lower, and the serum levels of FSH were
      markedly higher than those of the SHAM group and EST group, respectively. In the
      MOD group, the serum levels of IL-2 and IL-8 were significantly lower than those
      of the RA group, EST group and SHAM group (P<0.05), and no marked differences
      existed among RA group, EST group and SHAM group in the serum levels of IL-2 and
      IL-8 (P>0.05). The uterine weight of the rats in the RA group, EST group and SHAM
      group were significantly higher than those of the rats in MOD group (P<0.05).
      There were no marked differences among the rats from RA group, EST group and SHAM
      group on the uterine weight (P>0.05). It is concluded that RA can significantly
      improve the immune functions of the ovariectomized female rats, although it
      cannot change the sex hormones levels as significantly as estrogen. 

PMID- 24082320
TI  - Protective role of Artemisia afra aqueous extract on tissue antioxidant defense
      systems in streptozotocin-induced diabetic rats.
AB  - Changes in antioxidant capacity in the body as a result of oxidative stress play
      an important role in the development of diabetic complications. The aim of this
      study was to evaluate the effect of aqueous extract of Artemisia afra Jacq. ex
      Willd. on antioxidant defense systems in the liver and kidney of streptozotocin
      induced diabetic rats. Administration of the extract to diabetic rats for 21 days
      significantly reduced blood glucose levels and increased body weight. The
      diabetic animals exhibited decreased levels of glutathione reductase (GR),
      glutathione peroxidase (GPx), superoxide dismutase (SOD) and reduced glutathione
      (GSH) in the liver and kidney, which were restored to near normal levels
      following treatment with the herb. The increased levels of lipid peroxidation
      observed in the tissues of diabetic rats were also reverted back to near normalcy
      after administering the extract. These findings revealed the protective role of
      A. afra on tissues by reducing oxidative stress which could be attributed to its
      flavonoids content. The efficacy of the plant compared favourably well with
      glibenclamide, a standard hypoglycemic drug. 

PMID- 24082321
TI  - Complementary and alternative medicine usage in cancer patients in southeast of
      Turkey.
AB  - The aim of this study was to investigate the frequency of complementary and
      alternative medicine (CAM) methods and clinical characteristics in cancer
      patients in southeast of Turkey. A total of 324 patients (173 female) were
      enrolled to this study. Questionnaire was applied to all patients individually
      for approximately 15 minutes by a doctor. At least one CAM method was used by 62%
      (n=201) of the patients. 82.5% (n=166) of patients treated with CAM were using at
      least one herbal species. Likewise, 40.9% (68/166) of these patients were using
      herbal mixtures and 39.8% (66/166) of them were using single herbal as nettle
      (Urtica dioica) or its seed, 19.3 % (32/166) of them were using other herbals.
      CAM methods were preferred more frequently by the patients with metastatic stage
      (p=0.005), receiving palliative treatment (p<0.001), chemotherapy (p=0.020), in
      between 40-60 ages patient groups (p=0.002), and when duration of disease was
      lengthened (p=0.002). CAM use among cancer patients is quite common. Presence of
      metastatic cancer at diagnosis, receiving chemotherapy and palliative treatment
      and long disease duration were found as main associated factors for CAM usage. 

PMID- 24082322
TI  - Tribal formulations for treatment of pain: a study of the Bede community
      traditional medicinal practitioners of Porabari Village in Dhaka District,
      Bangladesh.
AB  - The Bedes form one of the largest tribal or indigenous communities in Bangladesh
      and are popularly known as the boat people or water gypsies because of their
      preference for living in boats. They travel almost throughout the whole year by
      boats on the numerous waterways of Bangladesh and earn their livelihood by
      selling sundry items, performing jugglery acts, catching snakes, and treating
      village people by the various riversides with their traditional medicinal
      formulations. Life is hard for the community, and both men and women toil day
      long. As a result of their strenuous lifestyle, they suffer from various types of
      pain, and have developed an assortment of formulations for treatment of pain in
      different parts of the body. Pain is the most common reason for physician
      consultation in all parts of the world including Bangladesh. Although a number of
      drugs are available to treat pain, including non-steroidal, steroidal, and
      narcotic drugs, such drugs usually have side-effects like causing bleeding in the
      stomach over prolonged use (as in the case of rheumatic pain), or can be
      addictive. Moreover, pain arising from causes like rheumatism has no proper
      treatment in allopathic medicine. It was the objective of the present study to
      document the formulations used by the Bede traditional practitioners for pain
      treatment, for they claim to have used these formulations over centuries with
      success. Surveys were conducted among a large Bede community, who reside in boats
      on the Bangshi River by Porabari village of Savar area in Dhaka district of
      Bangladesh. Interviews of 30 traditional practitioners were conducted with the
      help of a semi-structured questionnaire and the guided field-walk method. It was
      observed that the Bede practitioners used 53 formulations for treatment of
      various types of pain, the main ingredient of all formulations being medicinal
      plants. Out of the 53 formulations, 25 were for treatment of rheumatic pain,
      either exclusively, or along with other types of body pain. A total of 65 plants
      belonging to 39 families were used in the formulations. The Fabaceae family
      provided 7 plants followed by the Solanaceae family with 4 plants. 47 out of the
      53 formulations were used topically, 5 formulations were orally administered, and
      1 formulation had both topical and oral uses. 8 formulations for treatment of
      rheumatic pain contained Calotropis gigantea, suggesting that the plant has
      strong potential for further scientific studies leading to discovery of novel
      efficacious compounds for rheumatic pain treatment. 

PMID- 24082323
TI  - Immunostimulating effect of aqueous extract of Amphypterygium adstringens on
      immune cellular response in immunosuppressed mice.
AB  - Amphypterygium adstringens is a Mexican tree known as cuachalalate whose bark is
      habitually used for the treatment of fresh wounds, gastric ulcers,
      gastrointestinal cancer and various inflammatory conditions. The aim of this
      study was to evaluate the immunostimulant effect of the aqueous extract of A.
      adstringens on immune cellular response in immunosuppressed mice. An aqueous
      extract from the bark of cuachalalate was administered into BALB/c mice for 10
      days. We assessed their immunostimmulant activity on cellular immune response by
      Delayed Type Hypersensitivity Response (DHT) to dinitrofluorobencene (DNFB) and
      by MTT assay. L5178Y lymphoma was used as immunossuppression model. An increase
      in DHT was observed after treatment with 10 and 100 mg/kg of the aqueous extract
      from A. adstringens oral treatment in lymphoma bearing mice. Splenocyte
      proliferation rate was significantly increased (2.5 time) in immunosuppresed mice
      treated with 10 mg/kg oral treatment compared with group that received vehicle
      only. The present study showed for the first time the aqueous extract from A.
      adstringens as a positive immunostimulant agent in lymphoma bearing mice and we
      demonstrated evidence to support the traditionally use of cuachalalate in
      conditions in which the immune system is depressed. 

PMID- 24082324
TI  - Active compound of Zingiber cassumunar Roxb. down-regulates the expression of
      genes involved in joint erosion in a human synovial fibroblast cell line.
AB  - Rheumatoid arthritis (RA) is a chronic inflammatory disease of the synovium. It
      is involved in up-regulation of pro-inflammatory cytokines and matrix
      metalloproteinases (MMPs), resulting in joint inflammation and erosion. Zingiber
      cassumunar Roxb. has long been used to reduce joint pain and inflammation. This
      study aimed to investigate the inhibitory activities of an active compound of Z.
      cassumunar, (E)-4-(3',4'-dimethoxyphenyl)but-3-en-1-ol (compound D), against
      cytokine-induced up-regulation of catabolic genes involved in cartilage
      degradation in RA. Synovial fibroblast cell line, SW982, was cultured in media
      containing interleukin-1beta (IL-1beta), in the presence or absence of compound D
      at the concentration range of 1 to 100 uM. After 24 hours, the cells were
      analyzed for the expressions of MMPs, IL-1beta and interleukin-1beta-converting
      enzyme (ICE) by RT-PCR. MMPs activities in the culture media were analyzed by
      zymographic techniques. Dexamethasone was used as the positive control. It was
      found that compound D at the concentration of 10 - 100 uM significantly decreased
      the mRNA expressions of MMP-1, -2, -3, and -13 which was induced by IL-1beta
      (P<0.05) concomitantly with a decrease in activities of these MMPs in the culture
      media. An increase in the mRNA expression of IL-1beta and ICE was also suppressed
      by compound D. The results suggest that the potent activities of this compound
      may be involved in the reduction of IL-1beta protein synthesis in both pro-form
      and active form which played an important role in up-regulation of MMPs. This
      study first revealed the chondroprotective activity of Z. cassumunar in the
      transcriptional level by suppressing cytokine-induced catabolic genes which
      caused cartilage erosion in RA. 

PMID- 24082325
TI  - The effects of pranayama, hatha and raja yoga on physical pain and the quality of
      life of women with multiple sclerosis.
AB  - In a clinical trial carried out on 60 women with multiple sclerosis, the
      researchers obtained data using survey questionnaires. In addition to demographic
      data, the Multiple Sclerosis Quality of Life-54 (MSQoL-54) instrument was used to
      determine how multiple sclerosis influences the quality of life of the studied
      women. Within the frame of this randomized controlled trial, the participants
      were divided into two equally sized groups (the case and the control group) in
      which the level of pain and the quality of life were evaluated. The case group
      exercised pain-managing Yoga methods for three months, keeping the pace of eight
      90-minute sessions per month. The control participants were subjected to no
      intervention. One month after the Yoga therapy, the level of pain and the quality
      of life were evaluated in both groups and compared to the baseline data. Data
      were analyzed using SPSS software and paired t-tests. After the Yoga therapy, the
      case group showed a significant improvement in physical pain management (P=0.007)
      and the quality of life (P=0.001) as compared to the control group. The results
      showed that Yoga techniques can alleviate physical pain and improve the quality
      of life of multiple sclerosis patients.

PMID- 24082326
TI  - Anticancer constituents and cytotoxic activity of methanol-water extract of
      Polygonum bistorta L.
AB  - This study was specifically designed to identify anticancer constituents in
      methanol-water extract of Polygonum bistorta L. and evaluate its cytotoxicity.
      For this purpose methanol-water (40:60 v/v) extract was subjected to conventional
      preparative high pressure liquid chromatography and 13 fractions were obtained.
      Constituents of obtained fractions were separated and identified with the help of
      GC-MS and LC-DAD-ESI-MS. Anticancer phenolic compounds such as gallic acid,
      protocatechuic acid, p-hydroxybenzoic acid, chlorogenic acid, vanillic acid,
      syringic acid, catechol, 4-methyl catechol, syringol and pyrogallol and fatty
      acids such as linoleic acid, myristic acid and palmitic acid were separated from
      different fractions. Fractions were evaluated for their cytotoxic activity on a
      rarely studied human hepatocellular carcinoma cell line (HCCLM3). 11 fractions
      showed good to strong cytotoxicity in a range of 200 ug/mL-800 ug/mL, whereas 2
      fractions did not show any activity even at 800 ug/mL and no anticancer
      constituent was detected from them. 50 percent growth inhibition (GI50) values
      for five most active fractions were calculated and results were in a range of
      86.5 (+/-3) ug/mL-126.8 (+/-3) ug/mL. 3 out of these 5 most active fractions were
      found to contain phenolic content in them whereas all other fractions containing
      phenolic content did possess cytotoxic activity that may suggest the importance
      of phenolic constituents in anticancer activity. Moreover, the results also
      showed a definite dose dependent relationship between amount of fractions and
      cytotoxic activity. 

PMID- 24082327
TI  - Effect of tao-hong-si-wu-tang, a traditional Chinese herbal medicine formula, on
      physical fatigue in mice.
AB  - Tao-Hong-Si-Wu-Tang (THSWT) is a famous traditional Chinese herbal medicine
      formula, which has traditionally been used in China for about one thousand years.
      The present study investigated the effect of THSWT on physical fatigue. 32 male
      mice were randomly divided into 4 groups with 8 in each group. All were
      administered orally and daily for 28 days. Group I received isotonic saline
      solution as control; Group II, III and IV obtained 5, 10 and 20ml/ kg body weight
      of THSWT solutions, respectively. After 28 days, the anti-physical fatigue effect
      of THSWT was evaluated by using a forced swimming test, along with the
      determination of blood lactic acid, blood urea nitrogen (BUN), liver glycogen and
      muscle glycogen contents. The data showed that THSWT could extend exhaustive
      swimming time of mice, as well as decrease the BLA and BUN contents and increase
      the liver glycogen and muscle glycogen contents. The results support that THSWT
      had anti-physical fatigue effect. 

PMID- 24082328
TI  - Effect of oral administration of Pheretima aspergillum (earthworm) in rats with
      cerebral infarction induced by middle-cerebral artery occlusion.
AB  - We investigated the curative effect of Pheretima aspergillum (earthworm, PA) on
      rats with middle cerebral artery occlusion (MCAo). The MCAo-induced cerebral
      infarction was established and its underlying mechanisms by counting the
      infarction areas and evaluating the rats' neurological status. Immunostaining was
      used to test the expression of NeuN, and glial fibrillary acidic (GFAP), S100B,
      and brain-derived neurotrophic factor (BDNF) proteins. Our results showed that
      oral administration of PA for two weeks to rats with MCAo successfully reduced
      cerebral infarction areas in the cortex and striatum, and also reduced scores of
      neurological deficit. The PA-treated MCAo rats showed greatly decreased neuronal
      death, glial proliferation, and S100B proteins in the penumbra area of the cortex
      and in the ischemic core area of the cortex, but BDNF did not changed. These
      results demonstrated novel and detailed cellular mechanisms underlying the
      neuroprotective effects of PA in MCAo rats. 

PMID- 24082329
TI  - Ethnopharmacological studies of Tribulus terrestris (Linn). in relation to its
      aphrodisiac properties.
AB  - Synergism and antagonism impact of different plant metabolites present in crude
      fruit extract of Tribulus terrestris 'the herbal Viagra' have been studied.
      Variability in plant composition, biomass and metabolites concentration in
      different modules was significantly contributed by spatial factor. However the
      edhaphic parameters also changes with both spatial and temporal factors
      significantly. Fruit is the officinal part and the fruit production significantly
      related with soil nitrogen (P<0.01), whereas the soil nitrogen and pH also
      influenced the alkaloid content in fruit (P<0.05). The linear relation between
      fruit protein and fruit alkaloid (P<0.01) also observed and the relationship in
      between different soil parameters were established. Bioassay work confirmed its
      aphrodisiac properties, and site III is suggested for maximum biomass and high
      concentration of different metabolites. 

PMID- 24082330
TI  - In vitro anticholinergic and antihistaminic activities of Acorus calamus Linn.
      leaves extracts.
AB  - The present investigation was aimed at determining the effects of hexane,
      acetone, methanol and aqueous extracts of Acorus calamus leaves (ACHE, ACAE, ACME
      and ACAQE) on cholinergic and histaminic system using isolated frog rectus
      abdominis muscle and guinea pig ileum. A dose dependent potentiation of Ach
      response (anticholinesterase like effect) was found with ACAE and ACME at 0.25,
      0.5, 0.75 and 1 mg/ml, but at higher dose of ACAE, ACME, ACAQE and ACHE (5, 20
      mg/ml) inhibit the Ach response (antinicotinic effect). These results revealed
      biphasic effect of Acorus calamus leaves extracts on acetylcholine induced
      contractile response in isolated frog rectus abdominis muscle preparation (i.e.
      potentiation effect at lower dose and inhibitory effect at higher dose). Studies
      on isolated guinea pig ileum demonstrated antihistaminic effect in a dose
      dependent manner (100-1000 ug/ml) with ACAE, ACME and ACAQE. In addition, the
      dose dependent inhibition of Ach response (antimuscarinic effect) was observed
      with ACAE and ACME. In conclusion, Acorus calamus leaves extracts exerts
      antinicotinic, anticholinesterase like activities in isolated frog rectus
      abdominis muscle and antihistaminic, antimuscarinic effect in guinea pig ileum.
      It has been suggested that these observed activities can be further studied for
      therapeutic potential of Acorus calamus leaves in the treatment of cognitive
      disorders and asthma. 

PMID- 24082332
TI  - Simultaneous determination of seven constituents in herbal prescription
      jaeumganghwa-tang using HPLC-PDA.
AB  - A simple and accurate high-performance liquid chromatographic method was applied
      to the quantitative analysis of seven components of the traditional herbal
      prescription Jaeumganghwa-tang (JGT), including 5-hydroxymethyl-2-furaldehyde,
      albiflorin, paeoniflorin, liquiritin, ferulic acid, nodakenin, and glycyrrhizin.
      All seven compounds were separated in less than 40 min on a Gemini C18 column at
      40 degrees C by gradient elution using 1.0% (v/v) aqueous acetic acid and
      acetonitrile containing 1.0% (v/v) acetic acid as mobile phase. The flow rate was
      1.0 mL/min and the detector was a photodiode array (PDA) set at 230 nm, 254 nm,
      280 nm, and 330 nm. The calibration curves showed good linearity (r (2) > 0.9998)
      in different concentration ranges. The recovery of each component was in the
      range of 91.47-102.62%, with relative standard deviations (RSDs, %) less than
      4.5%. The RSDs (%) for intra- and interday precision were 0.06-2.85% and 0.06
      2.83%, respectively. The concentrations of the seven components in JGT were in
      the range 0.74-5.48 mg/g. 

PMID- 24082331
TI  - Proapoptotic, anti-cell proliferative, anti-inflammatory and anti-angiogenic
      potential of carnosic acid during 7,12 dimethylbenz[a]anthracene-induced hamster
      buccal pouch carcinogenesis.
AB  - The present study has investigated the modulating effect of carnosic acid on the
      expression pattern of cell proliferative (proliferating cell nuclear antigen
      (PCNA) cyclin D1 and a transcription factor c-fos), apoptotic (p53, Bcl-2, Bax
      caspase -3 and 9), inflammatory (Nuclear factor kappa B (NFkappaB) and
      cyclooxygenase-2 (COX- 2) and angiogenic (vascular endothelial growth factor
      (VEGF) markers during 7,12-dimethylbenz[a]anthracene (DMBA)-induced hamster
      buccal pouch carcinogenesis. Oral tumors were developed in the hamsters buccal
      pouches by painting with 0.5% DMBA in liquid paraffin three times a week for 14
      weeks. Hundred per cent tumour formation (well-differentiated squamous cell
      carcinoma) accompanied by deregulation in the above mentioned molecular markers
      was noticed in hamsters treated with DMBA alone (tumour bearing hamsters). Oral
      administration of carnosic acid at dose of 10mg/kg bw to hamsters treated with
      DMBA not only completely prevented the tumour formation, but also corrected the
      abnormalities in the expression pattern of molecular markers. The present study
      suggests that carnosic acid might have inhibited the tumour formation by exerting
      anti-cell-proliferative, anti-inflammatory, anti-angiogenic and apoptotic
      potential during DMBA-induced hamster buccal pouch carcinogenesis. 

PMID- 24082333
TI  - Variation of antioxidant activity and phenolic content of some common home
      remedies with storage time.
AB  - The variation of antioxidant activity and total phenolic content of some plants
      commonly used as home remedies were screened on the basis of air drying time of
      (short term and long term air) the dried plant Ocimum sanctum (leaf), Cucumis
      sativus (Seed), and ethanolic extracts of Capsicum frutescens (Seed) and
      Coriandrum sativum (Seed). Antioxidant activities and total phenolic content
      values were estimated using DPPH reagent and Folin Ciocalteu reagent methods
      respectively. The antioxidant activity in short term air dried Ocimum sanctum
      plant methanol extract (IC50 = 0.03 +/- 0.01 mg/l) was the highest among the
      other plant extracts. However, Coriandrum sativum plant ethanol extract produced
      higher phenolic content (70.24+/-3.4/66.57+/-4.1 mg/g) than other plant extracts.
      It was found that there was no correlation between antioxidant and phenolic
      content of these plant extracts. 

PMID- 24082334
TI  - Acute and subchronic toxicity of Chantaleela recipe in rats.
AB  - Acute and subchronic toxicities of Chantaleela recipe were studied in both male
      and female rats. Oral administration of the extract at a single dose of 5,000
      mg/kg body weight (5 females, 5 males) did not produce signs of toxicity,
      behavioral changes, mortality or differences on gross appearance of internal
      organs. The subchronic toxicity was determined by oral feeding the test substance
      at the doses of 600, 1,200 and 2,400 mg/kg body weight for 90 days (10 females,
      10 males). No signs of abnormalities were observed in the test groups as compared
      to the controls. The test and control groups (on the 90(th) day) and the
      satellite group (on the 118(th) day) were analyzed by measuring their final body
      and organ weights, taking necropsy, and examining hematological parameters, blood
      clinical chemistry and histopathology features. The results suggest that
      Chantaleela recipe did not cause acute or subchronic oral toxicities to female
      and male rats. 

PMID- 24082335
TI  - An evaluation on levels of knowledge, attitude and behavior of people at 65 years
      and above about alternative medicine living in Ankara.
AB  - The aim was to determine the knowledge, attitude and behavioral levels of people
      at and above 65 years of age, living in Ankara (Turkey) about alternative
      medicine. The study was carried out between March - April 2010 through survey
      application of 200 participants by selective random sampling from the population.
      Data obtained as a result of the survey were analyzed by SPSS program. The study
      revealed that 83.5% of the participants believed in alternative therapy methods
      but 16.5% of them did not. It is concluded that herbal therapy methods are the
      most frequently used methods with a 63% rate among other alternative therapy
      methods. When status of the participants was analyzed it was found that it was
      found that 69% received the information about alternative medicines from their
      family while 53.5% received it from television This study revealed that
      alternative medicine is profoundly used by people above 65 years of age in
      Ankara. 

PMID- 24082336
TI  - Acute and subchronic toxicity study of tud-rak-ka-sai-puu recipe in rats.
AB  - Acute and subchronic toxicities of Tud-Rak-Ka-Sai-Puu (TR) recipe were studied in
      male and female rats. After 14 days of a single oral administration of test
      substance (5,000 mg/kg body weight), measurement of the body and organs weights,
      necropsy and health monitoring were performed. No signs and differences in the
      weights and behavior were observed relative to the control rats, suggesting that
      TR recipe in the dose of 5,000 mg/kg body weight does not produce acute toxicity.
      The subchronic toxicity was determined by oral feeding in male and female rats
      daily with the test substance at 2, 20, 200 and 2,000 mg/kg body weight for 90
      days. No defects of animal behavior were observed in the test groups. Both test
      and control groups (on the 90(th) day) as well as the satellite group (on the
      118(th) day) were analyzed by measuring their final body and organ weights,
      taking necropsy, and examining hematology, blood clinical chemistry, and
      microanatomy. These results together with the information of signs, behavior and
      health monitoring can lead to a conclusion that an oral administration of TR
      recipe at 2, 20, 200 and 2,000 mg/kg body weight for 90 days did not cause
      subchronic toxicity. 

PMID- 24082337
TI  - Antimicrobial activity and phytochemical study of Vernonia glabra (Steetz) Oliv.
      & Hiern. in Kenya.
AB  - Infectious diseases are prevalent and life threatening in Kenya. Majority of the
      sick are seeking herbal remedies in search of effective, safe, and affordable
      cure. This project aims to investigate the antimicrobial activity and presence of
      active phytochemical compounds in different parts of Vernonia glabra; a plant
      used by herbalists in various regions of Kenya, for the treatment of
      gastrointestinal problems. The plant sample was collected in January 2010 in
      Machakos, and different parts dried at room temperature under shade, ground into
      powder and extracted in Dichloromethane: Methanol in the ratio 1:1, and water.
      These crude extracts were tested against Staphylococcus aureus, Escherichia coli,
      Candida albicans, and Aspergillus niger for antimicrobial activity using disc
      diffusion technique. Minimum inhibitory concentrations (MICs) for active crude
      extracts were done using disc diffusion technique after the failure of agar and
      broth dilution methods. It was observed that the organic crude extracts of
      flower, leaf, stem, root, and/or entire plant, showed activity against at least
      one of the four micro-organisms screened, and at concentrations lower than the
      aqueous crude extracts. Organic crude extract of the leaf showed the highest
      activity against Staphylococcus aureus (mean inhibition zone of 1.85), recording
      higher activity than the commercially used standard antibiotic (Streptomycin mean
      inhibition zone of 1.30). The organic crude extract of flower showed significant
      activity only against S. aureus, with the lowest MIC of 1.5625 mg/100ul, compared
      to streptomycin with M.I.C of 6.25 mg/100ul. Thin Layer Chromatography
      Bioautography Agar-Overlay showed that, flower alkaloids (50% active), root
      sapogenins (43.8% active), and root terpenoids (38.5% active) were identified as
      the potential antibacterial compounds against S. aureus. These results suggest
      that, V. glabra contains phytochemicals of medicinal properties and justify the
      use of V. glabra in traditional herbal medicine for the treatment of microbial
      based diseases. However, research on toxicity which is missing in this study is
      recommended for V. glabra in order to verify, validate and document the safety of
      this medicinal plant to the society. 

PMID- 24082338
TI  - In vitro analysis of antioxidant activities of Oxalis corniculata Linn. fractions
      in various solvents.
AB  - As part of our search for natural antioxidants, this work presents an evaluation
      of antioxidant activities of methanolic extract of Oxalis corniculata and its sub
      fractions in hexane, chloroform, ethyl acetate, n-butanol and water. The total
      phenolic contents in terms of ug of gallic acid equivalents per mg of dried mass
      were approximately 21.0, 28.2, 34.5, 162.0, 70.0, and 49.2 in methanolic, hexane,
      chloroform, ethyl acetate, n-butanolic and aqueous fractions respectively, while
      the flavonoid contents in these solvents were 362.4, 214.1, 317.1, 177.1, 98.8
      and 53.5 respectively in terms of ug of rutin per mg of dried mass. In DPPH
      assay, the ethyl acetate fraction showed the highest free radical scavenging
      activity, 24.0% with 1 mg/mL concentration. The second strongest fraction was
      chloroform (21.5%). The EC50 and TEC50 values of the methanolic extract were 3.63
      mg/mL and 23 min respectively. The FRAP values in terms of ug of ascorbic acid
      equivalents per mg of dried mass for these solvents were 288.0, 1705.3, 437.1,
      72.0, 28.0, and 44.0 respectively while total antioxidant activity measured by
      phosphomolybdate assay in terms of ug of ascorbic acid equivalents per mg of
      dried mass were 50.0, 117.0, 78.6, 57.8, 3.4 and 8.3 respectively. All the
      samples showed remarkable ability to inhibit lipid peroxidation exhibiting much
      better and sustainable peroxidation inhibitory activity than the standard
      butylated hydroxyanisole. 

PMID- 24082339
TI  - Acarbose: a new option in the treatment of ulcerative colitis by increasing
      hydrogen production.
AB  - Acarbose, which is clinically widely used to treat Type 2 Diabetes, is thought to
      act at the small intestine by competitively inhibiting enzymes that delay the
      release of glucose from complex carbohydrates, thereby specifically reducing post
      prandial glucose excursion. The major side-effect of treatment with acarbose,
      flatulence, occurs when undigested carbohydrates are fermented by colonic
      bacteria, resulting in considerable amount of hydrogen. We propose that enteric
      benefits of acarbose is partly attributable to be their ability to neutralise
      oxidative stress via increased production of H2 in the gastrointestinal tract.
      Therefore, symptoms of ulcerative colitis in human beings can be ameliorated by
      acarbose. 

PMID- 24082340
TI  - Newer therapies for the treatment of metastatic breast cancer: a clinical update.
AB  - Breast cancer is the foremost common malignancy among the female population
      around the world. Female breast cancer incidence rates have increased since 1980,
      slowed in 1990, the rate of increase have leveled off since 2001. In spite of the
      advances in the early detection, treatment, surgery and radiation support, almost
      70% of the patients develop metastasis and die of the disease. Around 10% of the
      patients when diagnosed with breast cancer have metastases. Survival among the
      breast cancer patients have increased due to the introduction of novel single
      agent, combination of chemotherapeutic agents and targeted biologic agents, which
      is breast cancer specific. The staging of tumor-node-metastasis is significant
      for the prognosis and treatment. Predominantly the combination of
      chemotherapeutic regimen is given to improve the rate of clinical benefit and the
      overall survival rate. Novel mono-therapeutic options are being used often in
      metastatic setting as they will not be able to endure the toxicity of the
      combination regimen. Usually, endocrine therapy is recommended for hormone
      responsive breast cancer due to efficacy and favorable side effect profile but
      chemotherapy becomes an option when endocrine therapy fails. This review
      summarizes the newer therapeutic options for early breast cancer and advanced
      breast cancer that are pretreated heavily on other chemotherapeutic agents.
      Further it provides monotherapies and other emerging novel combination regime
      which can be opted for first line or second line setting. 

PMID- 24082341
TI  - Determination of Trace Metals, Moisture, pH and Assessment of Potential Toxicity
      of Selected Smokeless Tobacco Products.
AB  - The characterization and classification of smokeless tobacco products has been a
      continuously evolving process. This is based on a number of different parameters
      like nicotine content, moisture content, amount of heavy metals, pH, and in vitro
      cytotoxicity assays. Their contexts often vary between countries, research
      institutions, and legal requirements. The categorisation of these products is
      quite challenging due to the diffused sample sizes, diverse array of branded
      products on offer, and the absence of a centralized manufacturing facility. This
      study aims at a systematic classification of 10 smokeless tobacco product samples
      from the retail market based on their potential toxicity upon long-term use. The
      estimation of potential toxicity follows a well-established method that employs
      the concentration of toxic metals in the different samples. The potential
      toxicity as well as heavy metal concentrations of the smokeless tobacco products
      analysed was found to be much higher than acceptable limits. For instance, the
      levels of lead, cadmium, copper and zinc of 2.5, 1, 4 and 23 ppm, respectively,
      are well above their recommended limits. The results from the study indicate that
      chronic use of smokeless tobacco products is a significant health risk,
      especially in the vulnerable population. Further studies of this nature will help
      establish a toxicological fingerprint on the diverse class of products that
      floods the market now. 

PMID- 24082342
TI  - Water decoction of coptidis rhizoma prevents oxidative damage in erythrocytes of
      mice.
AB  - Coptidis Rhizoma (Coptis chinensis) has been reported to have antioxidative
      effect on hemolysis of erythrocytes induced by acetylphenylhydrazine in mice and
      rats. However, the ability of Coptidis Rhizoma to protect structure and function
      of erythrocytes membrane and morphology of erythrocytes against oxidative damage
      remains unknown. In this study, we undertook a characterization of antioxidative
      activity in erythrocytes membrane of Coptidis Rhizoma using an in vivo model of
      acetylphenylhydrazine-induced mice together with in vitro studies with 2,2-azo
      bis (2-amidinopropane) dihydrochloride-induced erythrocytes for further
      morphology characterization. Acetylphenylhydrazine-induced mice were treated
      intragastrically with Coptidis Rhizoma at doses of 0.3, 0.6, and 1.2 g/kg per day
      for 3 days and at the dose of 0.6 and 1.2 g/kg it showed that there was an
      increasing trend in membranes cytoskeletal proteins of band I-IV, especially a
      significant upregulation in band II. Significant increase in phosphatidylserine
      and phosphatidylcholine content at the dose of 1.2 g/kg Coptidis Rhizoma was
      obsereved. At all doses of Coptidis Rhizoma, the declined membrane fluidity of
      acetylphenylhydrazine-induced mice was significantly increased. In addition, at
      the dose of 1.2 g/kg Coptidis Rhizoma treatment showed a significant increase in
      Ca(2+)/Mg(2+)-ATPase activity and there was an increasing trend in the activity
      of Na(+)/K(+)-ATPase. In vitro, Coptidis Rhizoma protected erythrocytes from 2,2
      azo-bis (2-amidinopropane) dihydrochloride-induced hemolysis in a dose-dependent
      manner at concentrations of 0.25-1.5 mg/ml, and also significantly inhibited the
      2,2-azo-bis (2-amidinopropane) dihydrochloride-induced morphological alterations
      in mice erythrocytes. These results demonstrate that Coptidis Rhizoma is capable
      of protecting erythrocytes against oxidative damage probably by acting as an
      antioxidant and maintaining membrane integrity. 

PMID- 24082343
TI  - Dextran Carrier Macromolecules for Colon-specific Delivery of 5-Aminosalicylic
      Acid.
AB  - Present manuscript describes the sustained and targeted delivery of 5
      aminosalicylic acid to the distal ileum and proximal colon, using dextran (40
      kDa) as a carrier for targeting 5-aminosalicylic acid at the colonic site by
      attaching p-aminobenzoic acid and benzoic acid as linkers. Prepared conjugate
      were characterized by UV, HPLC, FT-IR, and (1)H NMR. The degree of substitution
      was estimated by complete hydrolysis of conjugates in borate buffer and in vitro
      hydrolysis study of conjugates was performed in different biological media. It
      was observed that 5-aminosalicylic acid alone have produced high incidence of
      gastric ulcer with high ulcer index whereas lower ulcer index was found for the
      dextran conjugates of 5-aminosalicylic acid. The release pattern of conjugates in
      3% w/v rat caecal content was confirmed the colon specificity of 5-aminosalicylic
      acid conjugates. 

PMID- 24082344
TI  - Stability-indicating HPLC Method for Simultaneous Determination of Montelukast
      and Fexofenadine Hydrochloride.
AB  - A simple, specific, accurate, and stability-indicating reversed-phase high
      performance liquid chromatographic method was developed for the simultaneous
      determination of montelukast and fexofenadine hydrochloride, using a
      Lichrospher((r)) 100, RP-18e column and a mobile phase composed of methanol:0.1%
      o-phosphoric acid (90:10 v/v), pH 6.8. The retention times of montelukast and
      fexofenadine hydrochloride were found to be 10.16 and 12.03 min, respectively.
      Linearity was established for montelukast and fexofenadine hydrochloride in the
      range of 2-10 MUg/ml and 24-120 MUg/ml, respectively. The percentage recoveries
      of montelukast and fexofenadine hydrochloride were found to be in the range of
      99.09 and 99.81%, respectively. Both the drugs were subjected to acid and base
      hydrolysis, oxidation, photolytic, and thermal degradation conditions. The
      degradation products of montelukast and fexofenadine hydrochloride were well
      resolved from the pure drug with significant differences in their retention time
      values. This method can be successfully employed for simultaneous quantitative
      analysis of montelukast and fexofenadine hydrochloride in bulk drugs and
      formulations. 

PMID- 24082345
TI  - Formulation development and dissolution rate enhancement of efavirenz by solid
      dispersion systems.
AB  - The aim of this study was to enhance the dissolution rate of efavirenz using
      solid dispersion systems (binary and ternary). A comparison between solvent and
      fusion method was also investigated. Solid dispersions of efavirenz were prepared
      using polyethylene glycol 8000, polyvinylpyrrolidone K30 alone and combination of
      both. Tween 80 was incorporated to obtain a ternary solid dispersion system.
      Dissolution tests were conducted and evaluated on the basis of cumulative
      percentage drug release and dissolution efficiency. Physicochemical
      characterizations of the solid dispersions were carried out using differential
      scanning calorimetric, powder X-ray diffraction, Fourier transform infrared
      spectroscopy, and scanning electron microscopy. Dissolution was remarkably
      improved in both systems compared to pure efavirenz (P<0.05). An optimum ratio
      was identified at a drug:polymer of 1:10. Incorporation of Tween 80 to 1:10
      formulations formed using solvent method showed further improvement in the
      dissolution rate. Physicochemical characterization results suggested that
      efavirenz existed in the amorphous form in all the solid dispersion systems
      providing evidence of improvement in dissolution. No statistically significant
      difference (P>0.05) in dissolution was observed between the two methods. Binary
      and ternary solid dispersion systems both have showed a significant improvement
      in the dissolution rate of efavirenz. Formulations with only polyvinylpyrrolidone
      K30 showed best dissolution profile and 1:10 was identified as an optimum drug
      polymer weight ratio. 

PMID- 24082346
TI  - Analgesic and Micromeritic evaluations of SRMS-based oral Lipospheres of
      Diclofenac Potassium.
AB  - The objective of our work was to study the micromeritic properties of lyophilized
      diclofenac potassium-loaded lipospheres and to evaluate in vivo, the analgesic
      properties of diclofenac potassium in the lipospheres in addition to other in
      vitro properties. Solidified reverse micellar solutions were prepared by fusion
      using 1:1, 2:1, and 1:2% w/w of Phospholipon((r)) 90H and Softisan((r)) 154.
      Diclofenac potassium (1, 3, and 5% w/w) was incorporated into the solidified
      reverse micellar solutions. Solidified reverse micellar solutions-based
      lipospheres were formulated by melt homogenization techniques using Ultra-Turrax
      homogenizer, and thereafter lyophilized to obtain water-free lipospheres. The
      lipospheres were characterized in terms of particle size and morphology,
      stability, thermal analysis, drug content, encapsulation efficiency, and loading
      capacity. The flow properties of the lipospheres were studied using both direct
      and indirect methods of assessing flow. The analgesic properties of the
      lipospheres were studied using the hot plate method. Results obtained showed that
      the yield of diclofenac potassium-loaded lipospheres was high and the particle
      size ranged from 0.61+/-0.07 to 2.55+/-0.04 MUm. The lipospheres had high
      encapsulation efficiency of 95%, which was affected by the amount of drug loaded,
      while the loading capacity increased with the increase in drug loading.
      Diclofenac potassium-loaded lipospheres exhibited poor flow. The formulations
      exhibited good analgesic effect compared with the reference and had 84 to 86%
      drug release at 13 h. The lipospheres based on solidified reverse micellar
      solutions could be used for oral delivery of diclofenac potassium. 

PMID- 24082347
TI  - Synthesis, Antimicrobial and cytotoxic activity of New Heterocyclic Hybrids Based
      on 2,5-Dimethylpyrrole and Pyrrole Scaffolds.
AB  - A series of 4-(2,5-dimethylpyrrol-1-yl)/4-pyrrol-1-yl benzoic acid hydrazide
      analogs, some derived triazoles, azetidinones, thiazolidinones, and pyrroles have
      been synthesized in good yields and structures of these compounds were
      established by IR, (1)H NMR, (13)C NMR, mass spectral, and elemental analysis.
      These compounds were evaluated for their preliminary in vitro antibacterial,
      antifungal, and antitubercular activity against Mycobacterium tuberculosis H37 Rv
      strain by the broth dilution assay method. Twenty one of these compounds
      displayed good antimicrobial activity, with a MIC value of 1-4 MUg/ml. Several
      compounds 4c, 8-10, 15b-15h, and 16b-16d exhibited good in vitro antitubercular
      activity with MIC value 1-2 MUg/ml. Further, some title compounds were also
      assessed for their cytotoxic activity (IC50) against mammalian Vero cell lines
      and A549 (lung adenocarcinoma) cell lines using the MTT assay method. The results
      revealed that these compounds exhibit antitubercular activity at non-cytotoxic
      concentrations. 

PMID- 24082348
TI  - Evaluation of Antioxidant Activity of Picrorhiza kurroa (Leaves) Extracts.
AB  - Picrorhiza kurroa is a well-known herb in Ayurvedic medicine. Although it shows
      antioxidant, antiinflammatory and immunomodulatory activities, it is most valued
      for its hepatoprotective effect. The rhizomes are widely used against indigestion
      problems since ancient times due to improper digestive secretions. Aim of this
      study was to explore antioxidant study of P. kurroa leaves for a new source of
      naturally occurring antioxidants. Two pure compounds, luteolin-5-O
      glucopyranoside (1) and picein (2) were isolated from butanol extract through
      column chromatography. Different extracts of P. kurroa leaves (ethanol, ethyl
      acetate, butanol) were quantified for isolated compound (2) by high-performance
      liquid chromatography. All the extracts and isolated compounds were evaluated for
      its antioxidant activity using two assays, 2,2-diphenyl-1-picrylhydrazyl radical
      and 2,2'-azino-bis(3-ethylbenzothiazoline-6-sulphonic acid) assay. The linear
      detection range was 1.56-200 MUg/ml for picein. The limit of detection and limit
      of quantification for picein were 2.34 and 7.81 MUg/ml, respectively. Butanol and
      ethyl acetate extract showed greater antioxidant activity as compare to ethanol
      extract. Compound 1 and ascorbic acid showed nearly similar antioxidant activity
      where as 2 showed no activity at standard concentration. The IC50 values for 2,2
      diphenyl-1-picrylhydrazyl radical and 2,2'-azino-bis(3-ethylbenzothiazoline-6
      sulphonic acid) assay for ascorbic acid, compound 1, ethanol extract and its
      different fractions (ethyl acetate and butanol) were found to be 0.81, 1.04,
      67.48, 39.58, 37.12 and 2.59, 4.02, 48.36, 33.24, 29.48 MUg, respectively. 

PMID- 24082349
TI  - Simultaneous Quantification of Six Major Flavonoids From Fructus sophorae by LC
      ESI-MS/MS and Statistical Analysis.
AB  - A new, sensitive and selective high-performance liquid chromatography-tandem mass
      spectrometric method has been developed for the determination of six major
      flavonoids including sophoricoside, genistin, genistein, rutin, quercetin,
      kaempferol in Fructus sophorae. Principal component analysis and hierarchical
      clustering analysis were used to classify and differentiate these samples.
      Chromatographic separation was performed on a C18 column with linear gradient
      elution of methanol and 0.05% acetic acid (v/v) at a flow rate of 0.8 ml/min. The
      detection was accomplished in the negative mode using multiple-reaction
      monitoring. The total run time was 8.0 min. Full validation of the assay was
      carried out including linearity, precision, accuracy, recovery, limit of
      detection and limit of quantification. The validated method was successfully
      applied to the simultaneous determination of these active components in Fructus
      sophorae. The results demonstrated that the quantitative difference in content of
      six active compounds was useful for chemotaxonomy of many samples from different
      sources and the standardization and differentiation of many similar samples.
      Simultaneous quantification of bioactive components by high-performance liquid
      chromatography-tandem mass spectrometric method coupled with chemometric
      techniques would be a well-acceptable strategy to comprehensively control the
      quality of Fructus sophorae. 

PMID- 24082350
TI  - Selective HPLC method development for soy phosphatidylcholine Fatty acids and its
      mass spectrometry.
AB  - A novel, efficient and simple approach for soy phosphatidylcholine analysis
      according to its fatty acid composition was studied with reverse-phase high
      performance liquid chromatography. The reverse-phase high-performance liquid
      chromatography analysis was performed isocratically using UV detector and simple
      mobile phase solvents consisting of isopropyl alcohol, methanol, and deionized
      water in the proportion of 70:8:22 v/v. The uniqueness of the proposed method was
      the separation of individual fatty acids of soy phosphatidylcholine. The high
      performance liquid chromatography method for soy phosphatidylcholine was
      validated for linearity with correlation coefficient of above 0.99 for all the
      peaks separated according to their fatty acid composition. The intra-day and the
      inter-day precision studies provided the relative standard deviation of less than
      2%. The limit of detection and limit of quantitation values were also calculated
      for all the resolved peaks of soy phosphatidylcholine. Also system performance
      parameters such as number of theoretical plates, capacity factor, tailing factor,
      separation factor, and peak resolution were studied systematically and found well
      within the acceptable range. The proposed high-performance liquid chromatography
      method was successfully applied to soy phosphatidylcholine extracted and purified
      from deoiled soy lecithin without any interference of impurities or solvent
      peaks. Individually, the collected peaks of sample soy phosphatidylcholine were
      subjected for mass spectroscopy. The mass spectra showed all the peaks having
      different saturated or unsaturated fatty acid chains attached to
      glyerophosphocholine moiety of soy phosphatidylcholine. The method developed is
      economic and well suited for estimation of soy phosphatidylcholine with its fatty
      acid composition. 

PMID- 24082351
TI  - Acute and Subchronic Toxicity Study of Tamra Bhasma (Incinerated Copper) prepared
      from Ashodhita (Unpurified) and Shodhita (Purified) Tamra in Rats.
AB  - The use of metals in traditional medicines is very often seen as matter of
      concern these days, especially the Bhasma preparations which are always under
      stringent observations for containing highly reactive inorganic elements such as
      lead, mercury, arsenic and others. One of the Bhasma extensively used in routine
      Ayurvedic practice is Tamra (copper) bhasma. If it is not prepared properly or
      Shodhana procedure is not done properly, it acts as a poison. To indicate its
      toxic potential, Ashtamahadoshas (eight major ill effects) have been quoted in
      classics and due emphasis have been given to its Shodhana procedure. In the
      present study, Tamra bhasma prepared from Shodhita and Ashodhita Tamra was
      subjected to oral toxicity study to ascertain the role of Shodhana process on
      safety profile of Tamra bhasma on subchronic administration to albino rats. Both
      the samples were administered to rats for 45 consecutive days at the doses of
      5.5, 27.5, and 55 mg/kg. Animals were sacrificed on 46(th) day and parameters
      like hematological, serum biochemical, and histopathology of various organs were
      studied. Results showed that Tamra bhasma prepared from Ashodhita Tamra has
      pathological implications on different hematological, serum biochemical and
      cytoarchitecture of different organs even at therapeutic dose level (5.5 mg/kg).
      Whereas, Tamra bhasma prepared from Shodhita Tamra is safe even at five-fold to
      therapeutic equivalent doses (27.5 mg/kg). These observations emphasize the role
      of Shodhana and importance of dose in expression of toxicity of the medicinal
      preparations. 

PMID- 24082352
TI  - Synthesis and pharmacological evaluation of antiinflammatory mutual amide
      prodrugs.
AB  - Nonsteroidal antiinflammatory drugs have been widely used for the management of
      inflammation, pain and nociception. Gastric intolerance caused by most of the
      nonsteroidal antiinflammatory drugs used today restricts their use. Several
      approaches have been proposed to modify the parent nonsteroidal antiinflammatory
      drugs molecule in order to reduce their gastric toxicity. Oral prodrug approach
      is one of such approaches. In the present work three nonsteroidal
      antiinflammatory drugs viz. ibuprofen, diclofenac, and flurbiprofen were
      conjugated with sulfonamides like sulphamethoxazole and sulphanilamide via amide
      bond using dicyclohexylcarbodiimide coupling reaction. The synthesized prodrugs
      were screened for their analgesic and antiinflammatory activity using Eddy's hot
      plate, acetic acid-induced writhing and carrageenan-induced rat paw edema method,
      respectively. These prodrugs were also evaluated for their ulcerogenic potential.
      All synthesized prodrugs were found to be less ulcerogenic than their parent
      nonsteroidal antiinflammatory drugs and showed better activity profile in terms
      of analgesic and antiinflammatory activity as compared to their respective parent
      drugs. 

PMID- 24082353
TI  - Chronopharmacokinetics of puerarin in diabetic rats.
AB  - Puerarin injection has been widely used for clinic treatment of diabetes
      recently. To assess the relationship between the administration time of puerarin
      and the blood concentration of puerarin as well as its pharmacokinetic
      parameters, the diabetic rat model was used in current study. The rats were
      randomly divided into morning and evening groups according to the administration
      time. After the puerarin injection, blood glucose was tested in order to know
      whether the efficiency of puerarin was influenced by its concentration and
      pharmacokinetic parameters. Our results show that the average concentration of
      puerarin in the evening group is significantly higher than that in the morning
      group. The numbers of t1/2alpha, t1/2beta, CL and AUC(0-infinity) are
      significantly different between the morning and evening groups. The blood glucose
      level in the evening group was lower than that in the morning group. The speed of
      its onset is higher and the blood glucose level declines much more significantly
      in the evening group. These findings suggest that the concentration and
      pharmacokinetic parameters of puerarin affect its efficiency in diabetic rats.
      Therefore, it might be better to give puerarin in evening than in the morning for
      the mellitus treatment. 

PMID- 24082354
TI  - Nonisothermal kinetics analysis of the dehydration of ziprasidone hydrochloride
      monohydrate by thermogravimetry.
AB  - In the current work the kinetics of dehydration of ziprasidone hydrochloride
      monohydrate was studied by nonisothermal thermogravimetry. Ziprasidone
      hydrochloride monohydrate was heated from 30 to 150 degrees  with a heating rate
      of 5 degrees  per min under nitrogen gas atmosphere and weight loss data were
      collected. Powder X-ray difraction was used to characterize the solid before and
      after dehydration. The well accepted Coats-Redfern model fitting approach was
      applied to the thermogravimetry data for the kinetic analysis. Thirteen solid
      state reaction models were studied; among them one-dimensional diffusion model
      was found to be the best fit model for this reaction with an excellent
      correlation 0.9994. The Arrhenius parameters, activation energy, and pre
      exponential factor were determined, the values were found to be 28 k.cal/mol and
      9.53*10(13) sec(-1), respectively. 

PMID- 24082355
TI  - Development and Validation of a HPTLC Method for Simultaneous Quantitation of
      Flunarizine Dihydrochloride and Propranolol Hydrochloride in Capsule Dosage Form.
AB  - A simple, precise, accurate, and rapid high-performance thin layer
      chromatographic method has been developed and validated for the simultaneous
      quantitation of flunarizine dihydrochloride and propranolol hydrochloride in a
      combined capsule dosage form. The method was carried out on precoated silica gel
      60 F254 TLC aluminum plate, (20*10 cm(2)). The solvent system was ethyl
      acetate:methanol:glacial acetic acid in the proportion of 8:1:1, (v/v/v). R f
      value for flunarizine dihydrochloride and propranolol hydrochloride was found to
      be 0.62+/-0.02 and 0.18+/-0.02, respectively. The linearity regression analysis
      for calibration showed 0.999 and 0.999 for flunarizine dihydrochloride and
      propranolol hydrochloride with respect to peak area and height in the
      concentration range of 50-350 ng/spot and 500-3500 ng/spot, respectively.
      Accuracy of recovery studies was found to be 98-100.28 and 99.11-99.45% for
      flunarizine dihydrochloride and propranolol hydrochloride, respectively. The
      amounts of drug in marketed formulation were 100.5 and 101.25% of flunarizine
      dihydrochloride and propranolol hydrochloride, respectively. The method developed
      can be used for routine analysis in bulk drug and capsule dosage form. 

PMID- 24082356
TI  - Physicochemical Characterization and Antioxidant Activity of Essential Oils of
      Guggul (Commiphora wightii) Collected from Madhya Pradesh.
AB  - The present study reports physicochemical characterization and antioxidant
      activity of essential oils extracted from guggul (Commiphora wightii) exudates
      collected from different places in Madhya Pradesh, India. The guggul exudates
      were hydrodistilled for 3-4 h in Clevenger apparatus. The oil obtained was dried
      over anhydrous Na2SO4 and stored at 4 degrees  until testing. Before extraction
      of oils from the exudates, their % moisture and tristimulus values of the colors
      namely L (white-black), a (green-red) and b (blue-yellow) were determined.
      Physicochemical characterization of the extracted oils was carried out to
      determine their solubility, yield%, acid value (mg/KOH/g), saponification value
      (mg/KOH/g), ester value, iodine value (g/g), peroxide value (mEq/kg) and Fourier
      transformed infrared analyses. The storage-effect on the % moisture and
      tristimulus values of the colors of guggul exudates as also the % oil yield and
      physicochemical parameters of the essential oils extracted from them, were
      studied using three different packaging materials viz., local plastic, low
      density polyethylene (200 G) and high density polyethylene (200 G). The
      antioxidant potential of extracted oils was evaluated by free radical scavenging
      activity using 1,1-diphenyl-2-picryl hydrazyl assay. 

PMID- 24082357
TI  - Stability-indicating Method for the Estimation of Riluzole in Tablets.
AB  - A stability-indicating reverse-phase high-pressure liquid chromatography method
      with photodiode array detector was developed and validated for estimation of
      riluzole in the bulk and tablet dosage forms. Riluzole was subjected to stress
      conditions (light, heat, humidity, acid/base hydrolysis and oxidation) and the
      stressed samples were analyzed by developed method. Degradation was observed in
      acidic, basic, oxidative and thermal conditions. The degradation products were
      well resolved from riluzole peak. An inertsil-ods column (250*4.6 mm, 5 MU) with
      a mobile phase comprising 0.02% v/v formic acid:acetonitrile(35:65 v/v) at a flow
      rate of 1.0 ml/min was used and eluents were monitored at 260 nm. The retention
      time of riluzole was 5.7 min. Complete validation for the method was carried out
      according to Internation Conference on Harmonization guidelines. Linearity was
      achieved in the range 10-50 MUg/ml with a correlation coefficient (r) 0.9998. The
      percent assay was 100.92 and mean percentage recovery was found to be 101.10. 

PMID- 24082358
TI  - In vitro and in vivo Antiinflammatory Activity of Clerodendrum paniculatum Linn.
      Leaves.
AB  - Preliminary phytochemical screening showed the presence of terpenes, flavonoids,
      tannins, alkaloids, phenolic acid, sterols, and glycosides. This study was
      intended to evaluate the antiinflammatory activity of various extracts of fresh
      leaves of Clerodendrum paniculatum Linn experimentally by in vitro (human red
      blood cell membrane stabilization method) and in vivo methods (0.1 ml of 1% w/v
      carrageenan-induced rat paw oedema model). Petroleum ether, chloroform, ethyl
      acetate, alcohol, and aqueous extracts were screened for in vitro
      antiinflammatory activity. Petroleum ether and chloroform extracts which showed,
      best in vitro antiinflammatory activity was screened for in vivo antiinflammatory
      activity at the dose level of 200 and 400 mg/kg. Indomethacin at the dose level
      of 10 mg/kg was used as reference standard drug. Both the extracts showed a dose
      dependent significant (P<0.001) reduction in paw edema when compared to the
      control, at all the time intervals and comparable to indomethacin (reference
      standard) treated group. The results of the present study demonstrate that
      petroleum ether and chloroform extracts possess significant (P<0.001)
      antiinflammatory potential which provide scientific basis for the traditional
      claims of Clerodendrum paniculatum Linn leaves as an antiinflammatory drug. 

PMID- 24082359
TI  - Effect of Eclipta alba on Acute Seizure Models: a GABAA-mediated Effect.
AB  - In the present study, anticonvulsant activity of methanol extract of Eclipta alba
      (10-200 mg/kg) was studied using pentylenetetrazole- and picrotoxin-induced
      seizure models. Mechanism of effect of methanol extract of Eclipta alba was
      further elucidated by studying its GABAA receptor modulatory activity and its
      effect on levels of GABA in mice brain. Methanol extract of Eclipta alba
      exhibited potent anticonvulsant activity but has saturation of its
      pharmacological activity at 50 mg/kg. At the concentration of 10 mg/ml,
      contractions induced in guinea pig ileum was blocked by picrotoxin, but it didn't
      not show any increase in GABA levels in mice brain after treatment. Hence, it can
      be concluded that methanol extract of Eclipta alba possesses potent
      anticonvulsant activity because of its positive modulatory effect on GABAA
      receptors. 

PMID- 24082360
TI  - Synthesis of High Oxidation State Molybdenum Imido Heteroatom-Substituted
      Alkylidene Complexes.
AB  - Reactions between Mo(NAr)(CHR)(Me2Pyr)-(OTPP) (Ar = 2,6-i-Pr2C6H3, R = H or
      CHCMe2Ph, Me2Pyr = 2,5-dimethylpyrrolide, OTPP = O-2,3,5,6-Ph4C6H) and CH2=CHX
      where X = B(pin), SiMe3, N-carbazolyl, N-pyrrolidinonyl, PPh2, OPr, or SPh lead
      to Mo(NAr)(CHX)-(Me2Pyr)(OTPP) complexes in good yield. All have been
      characterized through X-ray studies (as an acetonitrile adduct in the case of X =
      PPh2). The efficiencies of metathesis reactions initiated by
      Mo(NAr)(CHX)(Me2Pyr)(OTPP) complexes can be rationalized on the basis of steric
      factors; electronic differences imposed as a consequence of X being bound to the
      alkylidene carbon do not seem to play a major role. Side reactions that promote
      catalyst decomposition do not appear to be a serious limitation for Mo=CHX
      species.

PMID- 24082363
TI  - The diagnosis of exclusion: an ongoing uncertainty.

PMID- 24082364
TI  - On medical writing today.

PMID- 24082365
TI  - Red ribbon.

PMID- 24082366
TI  - Mitochondrial cardiomyopathy: pathophysiology, diagnosis, and management.
AB  - Mitochondrial disease is a heterogeneous group of multisystemic diseases that
      develop consequent to mutations in nuclear or mitochondrial DNA. The prevalence
      of inherited mitochondrial disease has been estimated to be greater than 1 in
      5,000 births; however, the diagnosis and treatment of this disease are not taught
      in most adult-cardiology curricula. Because mitochondrial diseases often occur as
      a syndrome with resultant multiorgan dysfunction, they might not immediately
      appear to be specific to the cardiovascular system. Mitochondrial cardiomyopathy
      can be described as a myocardial condition characterized by abnormal heart-muscle
      structure, function, or both, secondary to genetic defects involving the
      mitochondrial respiratory chain, in the absence of concomitant coronary artery
      disease, hypertension, valvular disease, or congenital heart disease. The typical
      cardiac manifestations of mitochondrial disease--hypertrophic and dilated
      cardiomyopathy, arrhythmias, left ventricular myocardial noncompaction, and heart
      failure--can worsen acutely during a metabolic crisis. The optimal management of
      mitochondrial disease necessitates the involvement of a multidisciplinary team,
      careful evaluations of patients, and the anticipation of iatrogenic and
      noniatrogenic complications. In this review, we describe the complex
      pathophysiology of mitochondrial disease and its clinical features. We focus on
      current practice in the diagnosis and treatment of patients with mitochondrial
      cardiomyopathy, including optimal therapeutic management and long-term
      monitoring. We hope that this information will serve as a guide for practicing
      cardiologists who treat patients thus affected.

PMID- 24082367
TI  - Mechanisms of chronic cardiac allograft rejection.
AB  - Chronic rejection in the form of cardiac allograft vasculopathy is one of the
      major factors that affects long-term graft and patient survival after heart
      transplantation. Whereas multiple factors contribute to the development of
      cardiac allograft vasculopathy, immunologic mechanisms play the predominant role
      in the chronic rejection process, because both alloimmune and autoimmune
      responses are causal factors. In addition, many nonimmune donor and recipient
      factors also affect the development of cardiac allograft vasculopathy, including
      hyperlipidemia, cytomegalovirus infection, baseline coronary artery disease, and
      the mechanism of brain death in the donor. Modern immunosuppression maintenance
      therapies have the potential to limit the development of cardiac allograft
      vasculopathy in the long term. Further research initiatives are needed to
      identify patient-specific immunosuppressive drug regimens and to elucidate
      factors that contribute to the chronic rejection of cardiac transplant
      allografts. 

PMID- 24082368
TI  - Cardiac allograft vasculopathy: a complex multifactorial sequela of heart
      transplantation.

PMID- 24082369
TI  - Feasibility of temporary biventricular pacing after off-pump coronary artery
      bypass grafting in patients with reduced left ventricular function.
AB  - In selected patients undergoing cardiac surgery, our research group previously
      showed that optimized temporary biventricular pacing can increase cardiac output
      one hour after weaning from cardiopulmonary bypass. Whether pacing is effective
      after beating-heart surgery is unknown. Accordingly, in this study we examined
      the feasibility of temporary biventricular pacing after off-pump coronary artery
      bypass grafting. The effects of optimized pacing on cardiac output were measured
      with an electromagnetic aortic flow probe at the conclusion of surgery in 5
      patients with a preoperative mean left ventricular ejection fraction of 0.26
      (range, 0.15-0.35). Atrioventricular (7) and interventricular (9) delay settings
      were optimized in randomized order. Cardiac output with optimized biventricular
      pacing was 4.2 +/- 0.7 L/min; in sinus rhythm, it was 3.8 +/- 0.5 L/min. Atrial
      pacing at a matched heart rate resulted in cardiac output intermediate to that of
      sinus rhythm and biventricular pacing (4 +/- 0.6 L/min). Optimization of
      atrioventricular and interventricular delay, in comparison with nominal settings,
      trended toward increased flow. This study shows that temporary biventricular
      pacing is feasible in patients with preoperative left ventricular dysfunction who
      are undergoing off-pump coronary artery bypass grafting. Further study of the
      possible clinical benefits of this intervention is warranted. 

PMID- 24082370
TI  - Elective percutaneous coronary intervention: the relationship between
      preprocedural blood glucose levels and periprocedural myocardial injury.
AB  - Regardless of the diabetic status of patients with coronary artery disease,
      hyperglycemia and hypoglycemia are adversely associated with cardiovascular
      events. The relationship between glucose levels and increased mortality risk in
      acute myocardial infarction has been shown through various glucose metrics;
      however, there is a dearth of multivariate analysis of the relationship between
      elective coronary angioplasty and preprocedural blood glucose levels. We
      evaluated the relationship between preprocedural blood glucose levels and
      myocardial injury in 1,012 consecutive patients who underwent elective
      percutaneous coronary angioplasty. The patients were classified into 4 glycemic
      groups on the basis of blood glucose levels measured immediately before the
      procedure: hypoglycemic, euglycemic, mildly hyperglycemic, and hyperglycemic.
      Samples for troponin I and creatine kinase-MB fraction were collected before each
      procedure and at 8, 16, and 24 hours after each procedure. Bivariate analysis
      revealed that postprocedural troponin I levels were significantly higher in the
      hyperglycemic group (P=0.027). Although postprocedural levels of creatine kinase
      MB fraction rose insignificantly in the hypoglycemic patients, our results showed
      that these patients were more likely to have postprocedural levels 2 to 5 times
      the upper limit of normal (P=0.013). We tentatively conclude that abnormally low
      preprocedural plasma glucose levels-together with a recent history of smoking-are
      associated with an increased incidence of periprocedural myocardial injury in
      patients undergoing elective percutaneous coronary intervention. 

PMID- 24082371
TI  - Cardiovascular disease in late survivors of tetralogy of fallot: a tertiary care
      center experience.
AB  - Patients with tetralogy of Fallot can survive to late adulthood; however, there
      are few data on cardiovascular outcomes in this population. We conducted a single
      center retrospective analysis of cardiovascular outcomes and risk factors in 208
      patients with tetralogy of Fallot to better evaluate the burden of cardiovascular
      disease in this group. Descriptive statistics were used to determine the
      prevalence of relevant cardiovascular risk factors and outcomes, including a
      composite analysis of cardiovascular disease. Rates and mean values from the
      American Heart Association 2011 Heart Disease and Stroke Statistics Update were
      used as population estimates for comparison. In tetralogy of Fallot patients,
      cardiovascular disease prevalence was not different from that found in the
      general population (40% vs. 36%, P=0.3). However, there was significantly more
      cardiovascular disease in tetralogy of Fallot men aged 20 to 39 years (30% vs.
      14%, P < 0.05) and in tetralogy of Fallot men aged 40 to 59 years (63% vs. 29%, P
      < 0.0001). This was due to higher prevalence of coronary disease (12% vs. 7%, P <
      0.05) and heart failure (16% vs. 2%, P < 0.0001). In particular, the increased
      prevalence of heart failure (regardless of pulmonary valve disease) accounts for
      the frequency of cardiovascular disease in tetralogy of Fallot men aged 20 to 59
      years. These data support the need to routinely screen young adult male survivors
      of tetralogy of Fallot for asymptomatic heart failure. Further studies are needed
      to determine the incidence, severity, and long-term effects of cardiovascular
      disease in the adult congenital heart disease population.

PMID- 24082372
TI  - Posterobasal left ventricular aneurysms: surgical treatment and long-term
      outcomes.
AB  - This retrospective study analyzes short- and long-term outcomes in 18 patients
      who underwent repair of posterobasal left ventricular aneurysm from January 1993
      through December 2009. As concomitant procedures, mitral reconstruction was
      performed in 4 patients, ventricular septal defect repair in 2 patients, and
      coronary artery bypass grafting in 17 patients. In regard to surgical technique,
      10 patients underwent patch repair and 8 underwent closure by linear suture. The
      in-hospital mortality rate was 11% (2 patients). An intra-aortic balloon pump was
      placed postoperatively in 1 patient. One patient underwent reoperation for
      mediastinitis and 2 for bleeding. The 1-, 5-, and 10-year survival rates were
      82%, 76%, and 52%, respectively. Posterobasal left ventricular aneurysm repair
      can be performed with low short-term mortality rates and good long-term outcomes.
      It must be judged whether a linear repair or patch repair is better, in
      accordance with aneurysm size and the concomitant operative procedure, if any. 

PMID- 24082373
TI  - Cardiac effects of chronic graft-versus-host disease after stem cell
      transplantation.
AB  - Chronic graft-versus-host disease (GVHD) develops as a result of the immunologic
      response that donor T-lymphocytes generate against host tissue after allogeneic
      stem cell transplantation. We tried to elucidate the contribution of cardiac
      dysfunction to the high morbidity and mortality rates observed after GVHD. Forty
      patients who had undergone bone marrow transplantation were enrolled in this
      prospective study: 14 patients who had been diagnosed with chronic GVHD
      (manifestations beyond day 100 after hemopoietic cell transplantation) and 26
      patients who had not. All patients had undergone baseline echocardiography before
      bone marrow transplantation and were monitored. After the expected period of time
      had elapsed for GVHD after transplantation, these patients were divided into 2
      groups in accordance with whether or not they developed chronic GVHD. No
      significant differences were observed before bone marrow transplantation in the 2
      groups' broad attributes or in their laboratory and echocardiographic findings (P
      >0.05). After transplantation, high-sensitivity C-reactive protein levels and
      erythrocyte sedimentation rates were significantly higher in the chronic GVHD
      group (P < 0.001 and P=0.01, respectively). Mean left ventricular mass was 227 +/
      32.3 g in the GVHD group and 149.3 +/- 27.4 g in the non-GVHD group (P < 0.001).
      The E/A flow rate was significantly higher in the non-GVHD group. This study
      shows that chronic GVHD increases left ventricular mass and impairs left
      ventricular diastolic function in patients who have developed chronic GVHD. In
      addition, it shows that inflammatory markers increase to higher levels in these
      patients. Comprehensive studies with larger samples are needed to more fully
      elucidate the cardiac effects of this disease.

PMID- 24082374
TI  - One-stoma carinoplasty: right upper sleeve lobectomy with hemicarinectomy for
      resection of right-tracheobronchial-angle tumors.
AB  - Tracheobronchial-angle tumors involve the right main bronchus, the right upper
      lobar bronchus, and the lateral wall of the lower trachea. Resecting these tumors
      is one of the most complex procedures in thoracic surgery. In cases of high
      caliber mismatch, the selection of a suitable anastomotic technique can be
      challenging. We found that our use of a one-stoma carinoplasty technique overcame
      high-caliber mismatch after the resection of these tumors. From 2009 through
      2012, 8 men (mean age, 59 +/- 6.2 yr; range, 46-66 yr) underwent complete
      resection of non-small-cell right-tracheobronchial-angle tumors at our
      institution. In every case, right upper sleeve lobectomy, wedge carinal
      resection, and one-stoma carinoplasty were applied. After tumor resection, one
      patient with hemoptysis and bronchopleural fistula underwent a completion
      pneumonectomy and died 10 days postoperatively. Bronchoscopy was necessary in 2
      patients who had atelectasis in the contralateral lung. At a mean follow-up
      duration of 19.43 +/- 8.4 months (range, 0.2-27.1 mo), 6 patients were alive and
      free of disease. We conclude that our one-stoma carinoplasty technique enables
      the resection of tumors at the right tracheobronchial angle, with acceptable
      morbidity and mortality rates. This method saves the unaffected part of the
      ipsilateral lung and can overcome high-caliber mismatch. Because of these and
      other advantages, we suggest that using our method first might preclude having to
      perform a right carinal sleeve pneumonectomy or using Barclay's method. 

PMID- 24082375
TI  - Embolization of patent foramen ovale closure devices: incidence, role of imaging
      in identification, potential causes, and management.
AB  - Transcatheter patent foramen ovale (PFO) closure is an alternative to
      antiplatelet or anticoagulative therapy in patients with cryptogenic stroke, and
      it is associated with a small incidence of periprocedural sequelae. Because
      embolization of PFO closure devices is a very rare procedural complication, data
      on its frequency, causes, and management are sparse. We sought to review the
      medical literature and the cases of PFO closure-device embolization at our
      institution with the aim of identifying likely problems and reporting potential
      solutions. Out of 310 adult patients who underwent transcatheter PFO closure from
      June 2002 through April 2011, there were 2 cases (0.6%) of PFO closure-device
      embolization. In both patients, hypermobile septum primum and thick septum
      secundum were present. In one patient, failure to use a sizing balloon might have
      resulted in an underestimation of the PFO's size. In both patients, device
      embolization was identified in a timely fashion, the embolized device was safely
      retrieved, and the PFO was percutaneously closed with success. The incidence of
      PFO closure-device embolization is very low. The cases described here underscore
      the importance of imaging in the identification of morphologic predispositions to
      closure-device malpositioning, in the recognition of impending embolization, and
      in the timely management of embolization. 

PMID- 24082376
TI  - Concomitant transapical mitral valvuloplasty and CentriMag assist device
      placement: in a "no-option" patient.
AB  - Left ventricular assist devices and percutaneous valve interventions have
      radically changed the treatment of advanced heart disease and minimized surgical
      morbidity in patients with end-stage heart failure who would not survive
      conventional surgery. We describe a successful approach to the simultaneous
      placement of a percutaneous left ventricular assist device and mitral
      valvuloplasty in a decompensated patient with end-stage ischemic cardiomyopathy,
      severe peripheral arterial disease, porcelain aorta, and severe mitral and aortic
      disease. 

PMID- 24082377
TI  - First case of Fusobacterium necrophorum endocarditis to have presented after the
      2nd decade of life.
AB  - Fusobacterium necrophorum, an obligate, anaerobic, filamentous, gram-negative
      rod, is thought to be a normal inhabitant of the mucous membranes in human
      beings. Fusobacterium species have been implicated in cases of Lemierre syndrome
      and other pathologic conditions. Their reported association with infective
      endocarditis is extremely rare. We describe the case of a previously healthy 34
      year-old man who emergently presented with flu-like symptoms and dyspnea on
      exertion. He had recently undergone a dental procedure. Empiric antibiotic
      therapy was initiated. Blood cultures were positive for metronidazole-resistant
      F. necrophorum. A transesophageal echocardiogram revealed 2 mobile vegetations on
      the mitral valve. Despite the antibiotic therapy, the patient's respiratory
      status worsened and, after 3 weeks, he died. On the basis of the organism's
      pathophysiology and the patient's recent dental procedure, the oral cavity was
      the likely source of the bacteremia. Our patient's case underscores the
      importance of recognizing Fusobacterium bacteremia as a possible cause of
      endocarditis. To our knowledge, this is the first reported case of monomicrobial
      F. necrophorum endocarditis to have presented in a patient after the 2nd decade
      of life. In addition, it is apparently only the 4th report of F. necrophorum
      mitral valve endocarditis with case results derived from modern culture
      techniques. 

PMID- 24082378
TI  - Sudden unilateral vision loss arising from calcified amorphous tumor of the left
      ventricle.
AB  - Calcified amorphous tumor of the heart is a very rare non-neoplastic
      intracavitary mass. The clinical presentation is similar to that of other cardiac
      masses. The precise cause and best approach to treatment remain unclear. We
      describe a case of cardiac calcified amorphous tumor presenting with refractory
      unilateral vision loss that was successfully treated by surgical excision. To our
      knowledge, this is only the 2nd reported case of retinal arterial embolism due to
      cardiac calcified amorphous tumor in the English-language literature. 

PMID- 24082379
TI  - Rapid growth of left atrial myxoma after radiofrequency ablation.
AB  - Atrial myxoma is the most common benign tumor of the heart, but its appearance
      after radiofrequency ablation is very rare. We report a case in which an
      asymptomatic, rapidly growing cardiac myxoma arose in the left atrium after
      radiofrequency ablation. Two months after the procedure, cardiovascular magnetic
      resonance, performed to evaluate the right ventricular anatomy, revealed a 10 *
      10-mm mass (assumed to be a thrombus) attached to the patient's left atrial
      septum. Three months later, transthoracic echocardiography revealed a larger
      mass, and the patient was diagnosed with myxoma. Two days later, a 20 * 20-mm
      myxoma weighing 37 g was excised. To our knowledge, the appearance of an atrial
      myxoma after radiofrequency ablation has been reported only once before. Whether
      tumor development is related to such ablation or is merely a coincidence is
      uncertain, but myxomas have developed after other instances of cardiac trauma. 

PMID- 24082380
TI  - Atrial myxoma in a patient with hypertrophic cardiomyopathy.
AB  - Atrial myxoma is the most common primary cardiac tumor. Patients with atrial
      myxoma typically present with obstructive, embolic, or systemic symptoms;
      asymptomatic presentation is very rare. To our knowledge, isolated association of
      atrial myxoma with hypertrophic cardiomyopathy has been reported only once in the
      English-language medical literature. We report the case of an asymptomatic 71
      year-old woman with known hypertrophic cardiomyopathy in whom a left atrial mass
      was incidentally identified on cardiac magnetic resonance images. After surgical
      excision of the mass and partial excision of the left atrial septum,
      histopathologic analysis confirmed the diagnosis of atrial myxoma. The patient
      was placed on preventive implantable cardioverter-defibrillator therapy and
      remained asymptomatic. The management of asymptomatic cardiac myxoma is a topic
      of debate, because no reports definitively favor either conservative or surgical
      measures. 

PMID- 24082382
TI  - Retrograde percutaneous closure of a ventricular septal defect after myectomy for
      hypertrophic obstructive cardiomyopathy.
AB  - In patients with hypertrophic obstructive cardiomyopathy, hemodynamically
      significant ventricular septal defect after septal myectomy is a rare sequela
      that warrants closure. Percutaneous closure provides a safer alternative to
      repeated sternotomy, which is associated with significant morbidity and mortality
      rates. We report a possibly unique case of successful retrograde percutaneous
      closure, with an AMPLATZER Muscular VSD Occluder, of an iatrogenic ventricular
      septal defect consequent to surgical therapy for hypertrophic obstructive
      cardiomyopathy. 

PMID- 24082381
TI  - Nonobstructive hypertrophic cardiomyopathy with left ventricular aneurysm: the
      role of cardiac magnetic resonance.
AB  - Hypertrophic cardiomyopathy with concomitant left ventricular aneurysm is rare
      and has important clinical implications, including an increased risk of sudden
      cardiac death. Most patients with this rare combination have obstructive
      hypertrophic cardiomyopathy, but we treated a 26-year-old woman who had
      nonobstructive hypertrophic cardiomyopathy and a family history of probable
      sudden cardiac death. In our patient, coronary angiograms showed distal occlusion
      of the left anterior descending coronary artery. Late gadolinium-enhanced cardiac
      magnetic resonance images showed scattered fibrosis within and beyond the left
      ventricular aneurysm. Precautionary therapy with an implantable cardioverter
      defibrillator yielded an uneventful outcome. Cardiac magnetic resonance has
      emerged as a promising method for diagnosing these aneurysms and detecting
      associated myocardial fibrosis, thereby enabling patient risk stratification and
      the determination of appropriate therapeutic options. We discuss the role of
      cardiac magnetic resonance imaging in the management of this rare clinical
      entity. 

PMID- 24082383
TI  - Ventricular fibrillation cardiac arrest due to 5-fluorouracil cardiotoxicity.
AB  - The antimetabolite chemotherapeutic agent 5-fluorouracil is used to treat a
      variety of cancers. Although 5-fluorouracil is generally well tolerated, its
      toxicity profile includes potential cardiac ischemia, vasospasm, arrhythmia, and
      direct myocardial injury. These actual or potential toxicities are thought to
      resolve upon cessation of the medication; however, information about the long
      term cardiovascular effects of therapy is not sufficient. We present the case of
      a 58-year-old man who had 2 ventricular fibrillation cardiac arrests, with
      evidence of coronary vasospasm and myocarditis, on his 4th day of continuous
      infusion with 5-fluorouracil. External defibrillation and cessation of the 5
      fluorouracil therapy resolved the patient's electrocardiographic abnormalities.
      In addition to reporting the clinical manifestations of 5-fluorouracil-associated
      cardiotoxicity in our patient, we discuss management challenges in patients who
      develop severe 5-fluorouracil-induced ventricular arrhythmias. 

PMID- 24082384
TI  - Cerebral protection against left ventricular thrombus during transcatheter aortic
      valve replacement in a patient with critical aortic stenosis.
AB  - Transcatheter aortic valve replacement is an increasingly common treatment of
      critical aortic stenosis. Many aortic stenosis patients have concomitant left
      ventricular dysfunction, which can instigate the formation of thrombus resistant
      to anticoagulation. Recent trials evaluating transcatheter aortic valve
      replacement have excluded patients with left ventricular thrombus. We present a
      case in which an 86-year-old man with known left ventricular thrombus underwent
      successful transcatheter aortic valve replacement under cerebral protection. 

PMID- 24082385
TI  - Tetralogy of fallot with dextrocardia and situs inversus in a 7-year-old boy.
AB  - Tetralogy of Fallot is one of the most frequently diagnosed congenital cardiac
      abnormalities; however, its association with dextrocardia and situs inversus is
      reported only rarely. We report a case of these findings in a 7-year-old boy,
      describe the patient's postoperative course, and review the medical literature
      relevant to these combined conditions. 

PMID- 24082386
TI  - Two cases of Bezold-Jarisch reflex induced by intra-arterial nitroglycerin in
      critical left main coronary artery stenosis.
AB  - The Bezold-Jarisch reflex, a well-described phenomenon, occurs upon the
      stimulation of intracardiac mechanoreceptors and is mediated by vagal afferent
      nerve fibers. Several factors can sensitize the cardiovascular system to develop
      this reflex, including acute myocardial ischemia, natriuretic peptides, and,
      rarely, nitroglycerin administration in the setting of acute myocardial
      infarction. The development of the Bezold-Jarisch reflex in the presence of
      severe coronary artery stenosis, specifically left main coronary artery stenosis,
      has not been described. We report 2 cases of patients who underwent elective
      coronary angiography and were given intra-arterial nitroglycerin during radial
      sheath insertion to reduce radial artery spasm. In both patients, bradycardia and
      hypotension developed along with diaphoresis, consistent with the Bezold-Jarisch
      reflex. Coronary angiography revealed critical (>90%) left main coronary artery
      stenosis in both patients. Critical left main coronary artery stenosis might
      sensitize mechanoreceptors or vagal afferents to the development of the Bezold
      Jarisch reflex after intra-arterial nitroglycerin use; however, the mechanism of
      this possible relationship is unclear. In addition to discussing our patients'
      cases, we review the medical literature relevant to the Bezold-Jarisch reflex. 

PMID- 24082387
TI  - Use of heparin alone in treating pulmonary emboli found in association with in
      transit right-heart thrombi in a nonagenarian.
AB  - In patients who present with pulmonary embolism, right-heart thrombus is a rare
      condition that is associated with increased mortality rates, compared with
      pulmonary embolism alone. Thrombolytic therapy has been associated with a
      survival benefit in previous studies of pulmonary embolism arising from right
      heart thrombus. However, older patients have been excluded from such studies
      because thrombolysis places them at excessively high risk of bleeding. We present
      a case, in a 92-year-old woman, of pulmonary embolism arising from right-heart
      thrombi that we successfully treated with heparin. 

PMID- 24082388
TI  - Aortic valve regurgitation that resolved after a ruptured coronary sinus aneurysm
      was patched.
AB  - Sinus of Valsalva aneurysms appear to be rare. They occur most frequently in the
      right sinus of Valsalva (52%) and the noncoronary sinus (33%). More of these
      aneurysms originate from the right coronary cusp than from the noncoronary cusp.
      Surgical intervention is usually recommended when symptoms become evident. We
      report the case of a 34-year-old woman who presented with a congenital, ruptured
      sinus of Valsalva aneurysm that originated from the noncoronary cusp. Moderate
      aortic regurgitation was associated with this lesion. Simple, direct patch
      closure of the ruptured aneurysm resolved the patient's left-to-right shunt and
      was associated with decreased aortic regurgitation to a degree that valve
      replacement was not necessary. Only trace residual aortic regurgitation was
      evident after 3 months, and the patient remained free of symptoms after 6 months.
      Our observations support the idea that substantial runoff blood flow in the
      immediate supra-annular region can be responsible for aortic regurgitation in the
      absence of a notable structural defect in the aortic valve, and that restoring
      physiologic flow in this region and equalizing aortic-cusp closure pressure can
      largely or completely resolve aortic insufficiency. Accordingly, valve
      replacement may not be necessary in all cases of ruptured sinus of Valsalva
      aneurysms with associated aortic valve regurgitation. 

PMID- 24082389
TI  - Noncoronary sinus of valsalva aneurysm rupture into right atrium.

PMID- 24082390
TI  - Giant right atrial mass: tumor or thrombus?

PMID- 24082391
TI  - Coronary sinus pacing for the management of right ventricular and atrial
      infarction with isolated right ventricular pulsus alternans.

PMID- 24082392
TI  - A rare pairing: myocardial noncompaction and congenital absence of pericardium.

PMID- 24082393
TI  - Candida parapsilosis bioprosthetic valve endocarditis inducing aortic valve
      stenosis.

PMID- 24082394
TI  - Technology or patients?

PMID- 24082396
TI  - Further traps to blood pressure measurement.

PMID- 24082397
TI  - Snatch-farrowed, porcine-colostrum-deprived (SF-pCD) pigs as a model for swine
      infectious disease research.
AB  - The current study tested the benefit of commercially available spray-dried bovine
      colostrum (The Saskatoon Colostrum Company, Saskatoon, Saskatchewan) in raising
      snatch-farrowed, porcine-colostrum-deprived (SF-pCD) pigs. In experiment 1, 12 SF
      pCD pigs received a liquid diet composed mainly of bovine colostrum from birth to
      day 10; 6 remained on the same liquid diet (COL), and the other 6 were fed a diet
      composed mainly of milk replacer (RPL) until weaning. In experiment 2, 12 SF-pCD
      pigs were fed mainly bovine colostrum before weaning; after weaning, 6 were fed a
      starter diet containing 20% (w/w) bovine colostrum powder (STARTER-COL), and the
      other 6 were fed a starter diet without any bovine colostrum (STARTER-CTRL) until
      termination (day 42 or day 49). In experiment 1 the COL pigs had significantly
      fewer fever-days than did the RPL pigs. In experiment 2 diarrhea, typhlocolitis,
      and pancreatic degeneration developed in 4 of the STARTER-COL pigs after weaning.
      In both experiments all the pigs fed mainly bovine colostrum before weaning
      survived until termination. All pigs tested free of swine influenza virus H1N1
      and H3N2, Porcine reproductive and respiratory syndrome virus, and Porcine
      parvovirus. In experiment 2 all the pigs tested free of Porcine circovirus type 2
      (PCV2), but some in both groups tested positive for Torque teno virus genogroups
      1 and 2. In conclusion, with the use of snatch-farrowing and bovine colostrum,
      pigs can be raised in the absence of porcine maternal antibodies with 100%
      survival and freedom from most porcine pathogens of biologic relevance. This
      model is potentially suitable for animal disease research. 

PMID- 24082398
TI  - Prediction of serum IgG concentration by indirect techniques with adjustment for
      age and clinical and laboratory covariates in critically ill newborn calves.
AB  - The objective of this study was to develop prediction models for the serum IgG
      concentration in critically ill calves based on indirect assays and to assess if
      the predictive ability of the models could be improved by inclusion of age,
      clinical covariates, and/or laboratory covariates. Seventy-eight critically ill
      calves between 1 and 13 days old were selected from 1 farm. Statistical models to
      predict IgG concentration from the results of the radial immunodiffusion test,
      the gold standard, were built as a function of indirect assays of serum and
      plasma protein concentrations, zinc sulfate (ZnSO4) turbidity and transmittance,
      and serum gamma-glutamyl transferase (GGT) activity. For each assay 4 models were
      built: without covariates, with age, with age and clinical covariates (infection
      and dehydration status), and with age and laboratory covariates (fibrinogen
      concentration and packed cell volume). For the protein models, dehydration status
      (clinical model) and fibrinogen concentration (laboratory model) were selected
      for inclusion owing to their statistical significance. These variables increased
      the coefficient of determination (R (2) ) of the models by >= 7% but did not
      significantly improve the sensitivity or specificity of the models to predict
      passive transfer with a cutoff IgG concentration of 1000 mg/dL. For the GGT
      assay, including age as a covariate increased the R (2) of the model by 3%. For
      the ZnSO4 turbidity test, none of the covariates were statistically significant.
      Overall, the R (2) of the models ranged from 34% to 62%. This study has provided
      insight into the importance of adjusting for covariates when using indirect
      assays to predict IgG concentration in critically ill calves. Results also
      indicate that ZnSO4 transmittance and turbidity assays could be used
      advantageously in a field setting. 

PMID- 24082399
TI  - A method to quantify infectious airborne pathogens at concentrations below the
      threshold of quantification by culture.
AB  - In aerobiology, dose-response studies are used to estimate the risk of infection
      to a susceptible host presented by exposure to a specific dose of an airborne
      pathogen. In the research setting, host- and pathogen-specific factors that
      affect the dose-response continuum can be accounted for by experimental design,
      but the requirement to precisely determine the dose of infectious pathogen to
      which the host was exposed is often challenging. By definition, quantification of
      viable airborne pathogens is based on the culture of micro-organisms, but some
      airborne pathogens are transmissible at concentrations below the threshold of
      quantification by culture. In this paper we present an approach to the
      calculation of exposure dose at microbiologically unquantifiable levels using an
      application of the "continuous-stirred tank reactor (CSTR) model" and the
      validation of this approach using rhodamine B dye as a surrogate for aerosolized
      microbial pathogens in a dynamic aerosol toroid (DAT). 

PMID- 24082400
TI  - Influence of temperature and organic load on chemical disinfection of Geobacillus
      steareothermophilus spores, a surrogate for Bacillus anthracis.
AB  - This study evaluated the influence of temperature and organic load on the
      effectiveness of domestic bleach (DB), Surface Decontamination Foam (SDF), and
      Virkon in inactivating Geobacillus stearothermophilus spores, which are a
      surrogate for Bacillus anthracis spores. The spores were suspended in light or
      heavy organic preparations and the suspension was applied to stainless steel
      carrier disks. The dried spore inoculum was covered with the disinfectants and
      the disks were then incubated at various temperatures. At -20 degrees C, the 3
      disinfectants caused less than a 2.0 log10 reduction of spores in both organic
      preparations during a 24-h test period. At 4 degrees C, the DB caused a 4.4 log10
      reduction of spores in light organic preparations within 2 h, which was about 3
      log10 higher than what was achieved with SDF or Virkon. In heavy organic
      preparations, after 24 h at 4 degrees C the SDF had reduced the spore count by
      4.5 log10, which was about 2 log10 higher than for DB or Virkon. In general, the
      disinfectants were most effective at 23 degrees C but a 24-h contact time was
      required for SDF and Virkon to reduce spore counts in both organic preparations
      by at least 5.5 log10. Comparable disinfecting activity with DB only occurred
      with the light organic load. In summary, at temperatures as low as 4 degrees C,
      DB was the most effective disinfectant, inactivating spores within 2 h on
      surfaces with a light organic load, whereas SDF produced the greatest reduction
      of spores within 24 h on surfaces with a heavy organic load. 

PMID- 24082401
TI  - Effect of a straw-derived xylooligosaccharide on broiler growth performance,
      endocrine metabolism, and immune response.
AB  - The aim of this work was to evaluate the effect of 3 levels of supplemental
      xylooligosaccharides (XOS) from straw on the growth performance, endocrine
      metabolism, and immune response of broiler chickens. Day-old, healthy Arbor Acres
      broilers (n = 192) received a basal diet of maize-soybean meal and, depending on
      the group to which they were allocated, no additive (control group) or the
      following experimental treatments for 59 d: treatment 1: 5 g XOS/kg; treatment 2:
      10 g XOS/kg; and treatment 3: 20 g XOS/kg. By day 59 the body weight gain of the
      chickens receiving treatment 2 had increased by 9.44% (P < 0.01) over the gain of
      the control group. The levels of serum triiodothyronine, thyroxine, and insulin
      on day 44 were significantly higher in the treatment groups than in the control
      group. The titers of antibody to the avian influenza H5N1 virus on day 24 were
      also significantly higher in the treatment groups than in the control group, and
      on day 59 the titer of the chickens receiving treatment 2 were still
      significantly increased (P < 0.05). Thus, the addition of XOS to feed can
      increase growth performance, enhance endocrine metabolism, and improve immune
      function in broiler chickens. 

PMID- 24082402
TI  - The rabbit as an infection model for equine proliferative enteropathy.
AB  - The objective of this study was to demonstrate the susceptibility of rabbits to
      Lawsonia intracellularis obtained from a case of clinical equine proliferative
      enteropathy (EPE). This is a preliminary step toward developing a rabbit
      infection model for studying pathogenesis and therapy of EPE in horses. Nine does
      were equally assigned to 3 groups. Animals in 2 groups (Group 1 and Group 2) were
      orally inoculated with different doses of cell-cultured L. intracellularis.
      Controls (Group 3) were sham-inoculated. Feces and blood were collected before
      the rabbits were infected and at 7, 14, and 21 days post-infection (DPI). Serum
      immunoglobulin G (IgG) titers were measured using an immunoperoxidase monolayer
      assay (IPMA) and fecal samples were analyzed with quantitative polymerase chain
      reaction (qPCR). A doe from each group was euthanized at 7, 14, and 21 DPI for
      collection and evaluation of intestinal samples. Tissues were stained by routine
      hematoxylin and eosin (H&E) method and immunohistochemistry (IHC) with L.
      intracellularis-specific mouse monoclonal antibody. At 14 DPI, serologic
      responses were detected in both infected groups, which maintained high titers
      through to 21 DPI. Lawsonia intracellularis DNA was detected in the feces of
      Group 2 on 7 DPI and in both infected groups on 14 DPI. Gross lesions were
      apparent in Group 1 and Group 2 on 14 DPI. Immunohistochemistry confirmed L.
      intracellularis antigen within cells of rabbits in Group 1 and Group 2 on 7, 14,
      and 21 DPI. No lesions, serologic response, shedding, or IHC labeling were found
      in Group 3 rabbits. This study describes an EPE rabbit model that simulates
      natural infection, as typical lesions, immune response, and fecal shedding were
      present. 

PMID- 24082403
TI  - Effects of vitamin E supplementation on cellular alpha-tocopherol concentrations
      of neutrophils in Holstein calves.
AB  - The effects of vitamin E supplementation on cellular alpha-tocopherol
      concentrations of neutrophils from Holstein calves and the mechanism of scavenger
      receptor class B type I (SR-BI)-mediated uptake of alpha-tocopherol were
      examined. Cellular alpha-tocopherol concentrations in vitamin E-treated calves
      increased from 3.5 +/- 0.38 to 7.2 +/- 0.84 MUg/10(7) cells, respectively, within
      14 d after vitamin E supplementation; these concentrations were significantly
      higher than those of control calves (P < 0.01). The expression indices of SR-BI
      [a major receptor that recognizes high-density lipoprotein (HDL)] mRNA in
      neutrophils were two to five times higher (P < 0.01) in neutrophils obtained from
      vitamin E-supplemented calves compared with those from control calves, and anti
      SR-B1 antibody, ranging from 0.1 to 1.0 MUg/mL, significantly (P < 0.01)
      decreased cellular alpha-tocopherol concentrations of neutrophils. Cytochalasin D
      and latrunculin B, major inhibitors of actin polymerization of neutrophils,
      significantly decreased cellular alpha-tocopherol concentrations of neutrophils
      (P < 0.01). Our results demonstrated that in vitamin E-supplemented calves: 1)
      alpha-tocopherol is mainly distributed with HDL, 2) alpha-tocopherol within HDL
      is recognized by SR-BI on the surface of neutrophils, and 3) rearrangement of the
      actin cytoskeleton is a crucial step for the uptake of alpha-tocopherol by
      neutrophils. 

PMID- 24082404
TI  - Preliminary study on factors influencing rabbit doe reproductive efficiency:
      Effect of parity, day of mating, and suckling on ovarian status and estrogen
      levels at day 6 of pregnancy.
AB  - The rabbit corpus luteum becomes an estradiol-dependent tissue by day 6 of
      gestation, and adequate estrogen is critical to avoid pregnancy failure. The aim
      of this study was to investigate the effect of parity (primiparous or
      multiparous), day of mating (11 or 21 d postpartum), and suckling status
      (suckling or nonsuckling) on various reproductive traits in hybrid rabbit does (n
      = 96). Ovarian structures on day 6 after coitus were evaluated by means of
      ultrasonography. Blood samples were collected that day, and the serum was
      analyzed for estradiol-17beta by radioimmunoassay (RIA). Parity and suckling had
      significant effects on mating rate (P < 0.01 and P < 0.05, respectively). More
      does accepted the male on day 11 than on day 21 (P < 0.05). Ovulation frequency
      was significantly affected by parity (P < 0.05), day of mating (P < 0.01), and
      suckling (P < 0.01). Fewer ovarian large follicles and lower estradiol-17beta
      levels were detected in suckling compared with nonsuckling rabbits (P < 0.01).
      Since estrogen concentrations are commonly used to assess follicular growth and
      steroidogenic capacity, the lower hormonal levels in the suckling rabbits may
      reveal poorer ovarian activity, which could result in reduced reproductive
      efficiency. Our observations confirm the existence of a partial antagonism
      between lactation and reproduction in rabbits. Further research is needed to
      elucidate these phenomena, including when artificial insemination is done.
      Ultrasonography could represent a noninvasive and reliable method for studying
      several reproductive functions and dysfunctions in rabbits. 

PMID- 24082405
TI  - The effect of nitrous oxide on the minimum alveolar concentration (MAC) and MAC
      derivatives of isoflurane in dogs.
AB  - This study investigated the effects of 70% nitrous oxide (N2O) on the minimum
      alveolar concentration (MAC) of isoflurane (ISO) that prevents purposeful
      movement, the MAC of ISO at which there is no motor movement (MACNM), and the MAC
      of ISO at which autonomic responses are blocked (MACBAR) in dogs. Six adult,
      healthy, mixed-breed, intact male dogs were anesthetized with ISO delivered via
      mask. Baseline MAC, MACNM, and MACBAR of ISO were determined for each dog using a
      supra-maximal electrical stimulus (50 V, 50 Hz, 10 ms). Nitrous oxide (70%) was
      then administered and MAC and its derivatives (N2O-MAC, N2O-MACNM, and N2O
      MACBAR) were determined using the same methodology. The values for baseline MAC,
      MACNM, and MACBAR were 1.39 +/- 0.14, 1.59 +/- 0.10, and 1.72 +/- 0.16,
      respectively. The addition of 70% N2O decreased MAC, MACNM, and MACBAR by 32%,
      15%, and 25%, respectively. 

PMID- 24082406
TI  - Oxidative stress, superoxide production, and apoptosis of neutrophils in dogs
      with chronic kidney disease.
AB  - Oxidative stress is a key component in the immunosuppression of chronic kidney
      disease (CKD), and neutrophil function may be impaired by oxidative stress. To
      test the hypothesis that in uremic dogs with CKD, oxidative stress is increased
      and neutrophils become less viable and functional, 18 adult dogs with CKD were
      compared with 15 healthy adult dogs. Blood count and urinalysis were done, and
      the serum biochemical profile and plasma lipid peroxidation (measurement of
      thiobarbituric acid reactive substances) were determined with the use of
      commercial reagents. Plasma total antioxidant capacity (TAC) was measured with a
      spectrophotometer and commercial reagents, superoxide production with a
      hydroethidine probe, and the viability and apoptosis of neutrophils with
      capillary flow cytometry and the annexin V-PE system. The plasma concentrations
      of cholesterol (P = 0.0415), creatinine (P < 0.0001), and urea (P < 0.0001) were
      significantly greater in the uremic dogs than in the control dogs. The hematocrit
      (P = 0.0004), urine specific gravity (P = 0.015), and plasma lipid peroxidation
      (P < 0.0001) were significantly lower in the dogs that were in late stages of CKD
      than in the control group. Compared with those isolated from the control group,
      neutrophils isolated from the CKD group showed a higher rate of spontaneous (0.10
      +/- 0.05 versus 0.49 +/- 0.09; P = 0.0033; median +/- standard error of mean) and
      camptothecin-induced (18.53 +/- 4.06 versus 44.67 +/- 4.85; P = 0.0066) apoptosis
      and lower levels of superoxide production in the presence (1278.8 +/- 372.8
      versus 75.65 +/- 86.6; P = 0.0022) and absence (135.29 +/- 51.74 versus 41.29 +/-
      8.38; P = 0.0138) of phorbol-12-myristate-13-acetate stimulation. Thus, oxidative
      stress and acceleration of apoptosis occurs in dogs with CKD, the apoptosis
      diminishing the number of viable neutrophils and neutrophil superoxide
      production. 

PMID- 24082407
TI  - Correlation of tumor-infiltrating lymphocytes to histopathological features and
      molecular phenotypes in canine mammary carcinoma: A morphologic and
      immunohistochemical morphometric study.
AB  - Abundant lymphocyte infiltration is frequently found in canine malignant mammary
      tumors, but the pathological features and immunophenotypes associated with the
      infiltration remain to be elucidated. The aim of the present study was to
      evaluate the relationship between lymphocyte infiltration, histopathological
      features, and molecular phenotype in canine mammary carcinoma (MC). The study was
      done with archived formalin-fixed, paraffin-embedded samples (n = 47) by
      histologic and immunohistochemical methods. The degree of lymphocyte infiltration
      was evaluated by morphologic analysis, and the T- and B-cell populations as well
      as the T/B-cell ratio were evaluated by morphometric analysis; results were
      compared with the histologic features and molecular phenotypes. The degree of
      lymphocyte infiltration was significantly higher in MCs with lymphatic invasion
      than in those without lymphatic invasion (P < 0.0001) and in tumors of high
      histologic grade compared with those of lower histologic grade (P = 0.045).
      Morphometric analysis showed a larger amount of T-cells and B-cells in MCs with a
      higher histologic grade and lymphatic invasion, but the T/B ratio did not change.
      Lymphocyte infiltration was not associated with histologic type or molecular
      phenotype, as assessed from the immunohistochemical expression of epidermal
      growth factor receptor 2, estrogen receptor, cytokeratin 14, and p63. Since
      intense lymphocyte infiltration was associated with aggressive histologic
      features, lymphocytes may be important for tumor aggressiveness and greater
      malignant behavior in the tumor microenvironment. 

PMID- 24082408
TI  - Clotting factor VIII (FVIII) and thrombin generation in camel plasma: A
      comparative study with humans.
AB  - The objective of this study was to characterize the highly elevated levels of
      clotting factor VIII (FVIII) in camel plasma. Whole blood was collected from
      healthy camels and factor VIII clotting activity (FVIII:C) assays were conducted
      using both the clotting and the chromogenic techniques. The anticoagulant citrate
      phosphate dextrose adenine (CPDA) produced the highest harvest of FVIII:C, the
      level of plasma factor VIII, compared to heparin:saline and heparin:CPDA
      anticoagulants. Camel FVIII can be concentrated 2 to 3 times in cryoprecipitate.
      There was a significant loss of camel FVIII when comparing levels of FVIII in
      camel plasma after 1 h of incubation at 37 degrees C (533%), 40 degrees C (364%),
      and 50 degrees C (223%). Thrombin generation of camel plasma is comparable to
      that of human plasma. It was concluded that camel plasma contains very elevated
      levels of FVIII:C, approaching 8 times the levels in human plasma, and that these
      elevated levels could not be attributed to excessive thrombin generation. Unlike
      human FVIII:C, camel FVIII:C is remarkably heat stable. Taken together, these
      unique features of camel FVIII could be part of the physiological adaptation of
      hemostasis of the Arabian camel in order to survive in the hot desert
      environment. 

PMID- 24082409
TI  - Differences in virulence gene expression between atypical enteropathogenic
      Escherichia coli strains isolated from diarrheic and healthy ruminants.
AB  - Differences in the pathogenicity of atypical enteropathogenic Escherichia coli
      (EPEC) strains may be due, at least partially, to different expression patterns
      of some virulence genes. To investigate this hypothesis, the virulence gene
      expression patterns of 6 atypical EPEC strains isolated from healthy and
      diarrheic ruminants were compared using quantitative real-time reverse
      transcription polymerase chain reaction after growing the bacteria in culture
      medium alone or after binding it to HeLa epithelial cells. Some virulence genes
      in strains from diarrheic animals were upregulated relative to their expression
      in strains from healthy animals. When bacteria were cultured in the presence of
      HeLa cells, the ehxA and efa1/lifA genes, previously associated with the
      production of diarrhea, were expressed at higher levels in strains from diarrheic
      animals than in strains from healthy animals. Thus, the expression levels of some
      virulence genes may help determine which atypical EPEC strains cause diarrhea in
      ruminants. 

PMID- 24082410
TI  - Migraine disability, healthcare utilization, and expenditures following treatment
      in a tertiary headache center.
AB  - Headache is among the most common disabling pain complaints. While many patients
      are managed in primary care or referral neurology practices, some patients have
      refractive situations that necessitate referral to a tertiary headache center.
      Increasing frequency of headache is strongly associated with increasing
      disability and workplace absenteeism as well as increased healthcare utilization.
      Previous studies have demonstrated that headache care in a dedicated tertiary
      center is associated with a decrease in headache frequency and improvement in
      other characteristics that persist over extended periods of time. Previous
      studies have not examined the impact of this treatment on subsequent healthcare
      utilization and associated expenditures. In this study we examined the changes in
      healthcare utilization and expenditures as well as the impact on disability and
      workplace productivity with treatment in a tertiary headache care center that
      used initial treatment settings of inpatient and outpatient care and considered
      the difference between those with episodic migraine and those with chronic
      migraine and its complications. Tertiary care was found to produce positive
      reductions in disability, healthcare utilization, and expenditures. These results
      suggest that earlier tertiary-level intervention may avoid the complications of
      migraine that occur in some patients and the increasing costs and utilization of
      care associated with higher disability. 

PMID- 24082411
TI  - Advance care planning knowledge and documentation in a hospitalized cancer
      population.
AB  - To have a better understanding of our patients' knowledge of advance directive
      planning and execution, as well as communication with their oncologists regarding
      their wishes, we conducted a survey on our inpatient hematology-oncology
      services. A total of 68 unique hospitalized patients with a diagnosis of cancer
      completed surveys. Surveys were given to all oncology patients regardless of
      their reason for admission. Overall, 29% of the patients reported having had a
      discussion with their oncologist regarding their wishes if they became seriously
      ill or near death. Of those who did have this conversation, the majority said
      that they, rather than their physician, initiated it. Although the vast majority
      of patients (97%) knew what a living will was, only 54% had one in place. Twenty
      patients had a discussion with their oncologist, and 14 of them (70%) had a
      living will. This percentage was higher than in the group that did not have a
      conversation with their physician (48%; 23 of 48 patients), but the difference
      was not statistically significant. Most cancer patients admitted to an inpatient
      oncology unit either did not have or did not recall having a discussion with
      their oncologist regarding end-of-life issues. This study gives us a baseline of
      information in evaluating future interventions directed to improve the quality of
      patient-physician communication regarding end-of-life planning. 

PMID- 24082412
TI  - Incidence and severity of respiratory insufficiency detected by transcutaneous
      carbon dioxide monitoring after cardiac surgery and intensive care unit
      discharge.
AB  - Patients undergoing coronary artery bypass surgery and/or heart valve surgery
      using a median sternotomy approach coupled with the use of cardiopulmonary bypass
      often experience pulmonary complications in the postoperative period. These
      patients are initially monitored in an intensive care unit (ICU) but after
      discharge from this unit to the ward they may still have compromised pulmonary
      function. This dysfunction may progress to significant respiratory failure that
      will cause the patient to return to the ICU. To investigate the severity and
      incidence of respiratory insufficiency once the patient has been discharged from
      the ICU to the ward, this study used transcutaneous carbon dioxide monitoring to
      determine the incidence of unrecognized inadequate ventilation in 39 patients
      undergoing the current standard of care. The incidence and severity of
      hypercarbia, hypoxia, and tachycardia in post-cardiac surgery patients during the
      first 24 hours after ICU discharge were found to be high, with severe episodes of
      each found in 38%, 79%, and 44% of patients, respectively. 

PMID- 24082413
TI  - Outcome assessment of 603 cases of concomitant inferior turbinectomy and Le Fort
      I osteotomy.
AB  - This retrospective study assessed the outcome of 603 patients undergoing partial
      inferior turbinectomies (PIT) in association with Lefort I osteotomy. The study
      included 1234 patients from a single private practice; these patients had
      dentofacial deformities and underwent Lefort I osteotomy procedures. For the full
      patient group, 888 patients (72%) were women; in the turbinectomy group, 403
      (67%) were women. The anteroposterior, transverse, and vertical dimensions of the
      mandible, maxilla, and occlusal plane of each subject were assessed, in addition
      to cephalometric analysis and determination of the presence or absence of
      temporomandibular joint disorders. PIT, when indicated, was performed after
      downfracture of the maxilla, providing access to the turbinates where
      approximately two thirds of the total turbinate volume was removed and
      septoplasty was completed if indicated. Hypertrophied turbinates causing
      significant nasal airway obstruction were present in 603 (49%) of the 1234
      patients undergoing Le Fort I osteotomy. The results of this study showed that
      PIT performed simultaneously with Le Fort I osteotomy is a safe method of
      managing nasal airway obstruction related to hypertrophied turbinates with
      minimal complications. 

PMID- 24082414
TI  - Copper deficiency (hypocupremia) and pancytopenia late after gastric bypass
      surgery.
AB  - Hypocupremia, or copper deficiency, is a rare and underrecognized cause of bone
      marrow dysplasia. Most cases of copper deficiency in adults occurred historically
      in patients receiving total parenteral hyperalimentation or total parental
      nutrition. More recently, with the obesity epidemic and the prevalence of gastric
      bypass, cases of malabsorption-related copper deficiency have occurred. Copper
      deficiency can lead to significant cytopenias and possible neurologic sequelae,
      which can be misdiagnosed and mismanaged. Unfortunately, a delay in diagnosis and
      appropriate treatment may lead to permanent neurologic damage. We describe a
      woman with previous gastric bypass surgery who presented with pancytopenia and
      bone marrow biopsy findings consistent with a myelodysplastic syndrome with
      excess blasts. She was found to be significantly copper deficient. With
      replacement copper therapy, her cytopenias quickly resolved. We discuss the
      distinctive clinical and hematologic features of this rare cause of significant
      cytopenias and provide recommendations for monitoring and treatment of such
      patients. Moreover, this case is an important reminder that bariatric patients
      should have routine follow-ups after surgery and continue dietary supplements
      indefinitely. 

PMID- 24082415
TI  - Isolated atrial amyloidosis and the importance of molecular classification.
AB  - Amyloid is identified microscopically as an amorphous extracellular hyaline
      material that exhibits "apple-green" birefringence with Congo red stains. Amyloid
      is not a chemically distinct entity, and currently available molecular methods
      are capable of identifying over 20 amyloidogenic precursor proteins. Some of the
      more common diseases associated with amyloidosis include plasma cell dyscrasias,
      chronic inflammatory disorders, hereditary-familial mutations involving
      transthyretin, Alzheimer's disease, and so-called "senile" or age-related
      amyloidosis. The amyloid deposits in these various diseases may be isolated to a
      single organ such as the heart or brain, or the amyloidosis may be systemic. The
      senile types of cardiac amyloidosis can result from overproduction of atrial
      natriuretic factor or from accumulation of otherwise normal or wild-type
      transthyretin. We present the case of an 83-year-old hospitalized woman with
      known atrial fibrillation and previous pacemaker implantation who had cardiac
      arrest unresponsive to attempted resuscitation. Autopsy disclosed prominent
      amyloidosis involving the left atrium, and subsequent molecular studies
      identified the amyloidogenic material as alpha atrial natriuretic factor. Since
      the clinical management and genetic implications of the various diseases
      associated with amyloidosis are markedly different, we stress the importance of
      molecular classification whenever possible. 

PMID- 24082416
TI  - The Heerfordt-Waldenstrom syndrome as an initial presentation of sarcoidosis.
AB  - Sarcoidosis is a granulomatous disease of unclear etiology, which commonly
      presents with cough, dyspnea, chest pain, fever, weight loss, arthralgias, and
      erythema nodosum. Heerfordt-Waldenstrom syndrome, a rare presentation of
      sarcoidosis, is characterized by the presence of parotid gland enlargement,
      facial palsy, anterior uveitis, and fever. Here we present a case of a 59-year
      old nonsmoking African American woman who presented with 3 days of progressively
      worsening left facial droop, difficulty swallowing, and blurred vision. Over the
      prior 4 months, she had had a productive cough, fevers, night sweats, and an
      unintentional 30-pound weight loss. Physical examination revealed a left facial
      droop involving the forehead, cheek, and chin with an inability to close the left
      eyelid. Her serum angiotensin-converting enzyme level was twice the upper limit
      of normal. Prominent hilar markings were identified on chest x-ray, but no focal
      opacity was seen. Fine-needle aspiration of a preauricular lymph node revealed
      noncaseating granulomas consistent with granulomatous lymphangitis. The patient
      was given a diagnosis of Heerfordt-Waldenstrom syndrome, or uveoparotid fever.
      Treatment with a high-dose steroid improved her parotid gland enlargement, facial
      palsy, and anterior uveitis. 

PMID- 24082417
TI  - Unusual dermal pleomorphic calcifications in a case of inflammatory breast
      carcinoma.
AB  - Inflammatory breast carcinoma is a rare and aggressive type of breast cancer that
      is definitively diagnosed by histologic evaluation showing invasive tumor cells
      in the dermal lymphatic system. Associated dermal calcifications are not
      typically identified. We report an unusual case in which inflammatory breast
      carcinoma led to the presence of pleomorphic dermal calcifications identified on
      the initial mammographic examination. 

PMID- 24082418
TI  - Basal cell adenoma of the breast.
AB  - Salivary gland-like neoplasms of the breast are a known entity. A single novel
      case of basal cell adenoma of the breast is presented, and the presentation,
      treatment, and morphologic features of this case are discussed. 

PMID- 24082419
TI  - Critical lower limb ischemia from an embolized Angio-Seal closure device.
AB  - Vascular closure devices were introduced in the early 1990s in an effort to
      reduce time to hemostasis, enable early ambulation, and improve the comfort of
      patients undergoing femoral artery access for endovascular procedures. Many of
      these devices leave a foreign component in or around the artery, which can lead
      to complications such as hematoma, pseudoaneurysm, infection, or limb ischemia.
      Here we present a case where device embolization led to arterial occlusion and
      critical limb ischemia. 

PMID- 24082420
TI  - The myth of the Bernheim syndrome.
AB  - The Bernheim syndrome has been a topic of discussion for over a century. It has
      been reported to be caused by severe rightward movement of the ventricular septum
      resulting in compression of the right ventricular cavity leading to right-sided
      heart failure without pulmonary congestion. Hemodynamic findings have been
      described in a few patients with the so-called Bernheim syndrome. We describe a
      patient in whom the ventricular septum dramatically decreased the size of the
      right ventricular cavity and yet peak systolic pressures in both the right
      ventricle and pulmonary trunk were identical. Thus, it is difficult to view the
      Bernheim syndrome as a real entity. 

PMID- 24082421
TI  - Fibromuscular dysplasia of the renal artery as a cause of secondary hypertension.
AB  - Fibromuscular dysplasia is an uncommon cause of secondary hypertension. When the
      resulting hypertension cannot be successfully treated with medications, balloon
      angioplasty has been shown to be successful by disrupting the "webs" of tissue in
      the renal artery. We present a case of secondary hypertension due to
      fibromuscular dysplasia and the successful treatment with balloon angioplasty. 

PMID- 24082422
TI  - Slow group beating.

PMID- 24082423
TI  - Continuous murmur and cardiac failure in a 53-year-old woman.

PMID- 24082424
TI  - Amlodipine overdose.
AB  - We describe the case of a 24-year-old woman who intentionally ingested between
      400 and 600 mg of amlodipine along with a large number of simvastatin and
      trazodone tablets. 

PMID- 24082425
TI  - Consults for conflict: the history of ethics consultation.
AB  - The very existence of ethics consultation reflects both the increasing complexity
      of modern medicine's ethical questions and our discomfort with the prospect of
      answering them alone. Two developments in the past century were instrumental in
      driving the development of ethics consultation-organ replacement therapy and
      intensive care. With the proliferation of extreme life-prolonging measures came
      the thorny difficulties in the withdrawal of such services or rationing when
      resources were poor. Insofar as "someone must," lamented Dr. Karen Teel (a
      pioneer of ethics consultation), the physician "is charged with the
      responsibility of making ethical judgments which we are sometimes ill-equipped to
      make." More than anything, ethics consultation has come to best satisfy a central
      desire of American health care-sharing the responsibility for tough decisions. 

PMID- 24082426
TI  - What's going on in dental education?

PMID- 24082427
TI  - An unforgettable, perpetual medical student, 1961.

PMID- 24082428
TI  - Facts and ideas from anywhere.

PMID- 24082429
TI  - Eosinophil as a protective cell in S. aureus ventilator-associated pneumonia.
AB  - Cell counts of leukocytes subpopulations are demonstrating to have an important
      value in predicting outcome in severe infections. We evaluated here the render of
      leukogram counts to predict outcome in patients with ventilator-associated
      pneumonia (VAP) caused by Staphylococcus aureus. Data from patients admitted to
      the ICU of Hospital Clinico Universitario de Valladolid from 2006 to 2011 with
      diagnosis of VAP caused by S. aureus were retrospectively collected for the study
      (n = 44). Leukocyte counts were collected at ICU admission and also at VAP
      diagnosis. Our results showed that nonsurvivors had significant lower eosinophil
      counts at VAP diagnosis. Multivariate Cox regression analysis performed by the
      Wald test for forward selection showed that eosinophil increments from ICU
      admission to VAP diagnosis and total eosinophil counts at VAP diagnosis were
      protective factors against mortality in the first 28 days following diagnosis:
      (HR [CI 95%], P): (0.996 [0.993-0.999], 0.010); (0.370 [0.180-0.750], 0.006).
      Patients with eosinophil counts <30 cells/mm(3) at diagnosis died earlier.
      Eosinophil counts identified survivors: (AUROC [CI 95%], P): (0.701 [0.519
      0.882], 0.042). Eosinophil behaves as a protective cell in patients with VAP
      caused by S. aureus.

PMID- 24082430
TI  - Assessing variance components in multilevel linear models using approximate Bayes
      factors: A case study of ethnic disparities in birthweight.
AB  - Racial/ethnic disparities in birthweight are a large source of differential
      morbidity and mortality worldwide and have remained largely unexplained in
      epidemiologic models. We assess the impact of maternal ancestry and census tract
      residence on infant birth weights in New York City and the modifying effects of
      race and nativity by incorporating random effects in a multilevel linear model.
      Evaluating the significance of these predictors involves the test of whether the
      variances of the random effects are equal to zero. This is problematic because
      the null hypothesis lies on the boundary of the parameter space. We generalize an
      approach for assessing random effects in the two-level linear model to a broader
      class of multilevel linear models by scaling the random effects to the residual
      variance and introducing parameters that control the relative contribution of the
      random effects. After integrating over the random effects and variance
      components, the resulting integrals needed to calculate the Bayes factor can be
      efficiently approximated with Laplace's method.

PMID- 24082431
TI  - Assessing surgical competence: A challenge.

PMID- 24082432
TI  - Prospective evaluation of risk factors for mortality in patients of Fournier's
      gangrene: A single center experience.
AB  - INTRODUCTION: Fournier's gangrene is an aggressive disease with high morbidity
      and mortality. The aim of this study was to assess risk factors associated with
      mortality among patients of Fournier's gangrene. MATERIALS AND METHODS: Between
      May 2011 and September 2012, all patients of Fournier's gangrene treated at our
      center were included in the study. All patients underwent emergency surgical
      debridement and received broad spectrum intravenous antibiotics. Their baseline
      characteristics, treatment, and follow-up data were recorded and analyzed.
      RESULTS: A total of 30 patients were included in the study. Of these, six
      patients (20%) died during the treatment. Age <55 years, total leukocyte count
      <15000 cumm, extent of the area involved, septic shock at admission, visual
      analog scale (VAS) <7 at admission, and Fournier gangrene severity index (FGSI)
      score <8 at admission were significantly associated with increased mortality.
      CONCLUSION: In patients of Fournier's gangrene, increased age, total leukocyte
      count, extent of the area involved, septic shock at admission, VAS score, and
      FGSI score at admission have a significant association with mortality.

PMID- 24082433
TI  - Pleated colposuspension: Our modification of Burch colposuspension.
AB  - INTRODUCTION: Burch colposuspension is a standard treatment for stress urinary
      incontinence. However, it is associated with recurrence and urinary retention. We
      describe a modification of this technique to overcome these problems and evaluate
      the results in comparison with the standard procedure. MATERIALS AND METHODS: A
      total of 145 patients with isolated stress urinary incontinence (SUI), underwent
      either our modified pleated colposuspension (PC); n = 97) or standard Burch
      colposuspension (BC) (n = 48). Description of PC: Three No. 0 non-absorbable
      sutures were placed in the side-to-side manner at the mid-urethral level with 0.5
      1.0 cm distance between them using double bites and were passed through the
      Cooper's ligament. The patients were followed-up every 6 months for SUI and
      genital prolapse evaluation. Successful surgery was defined as (1) No self
      reported SUI symptoms, (2) Negative Marshall's coughing test (MT), (3) No
      retreatment for SUI, (4) Absence of urodynamic SUI. In addition, failure was
      defined as the occurrence of urinary retention, use of catheter on 6-week visit,
      maximum flow rate >15 ml/s, flow time <60 s, or residual urine <100 ml. Data was
      compared using Student's paired test and Mantel-Haenzel's chi(2) test. P > 0.05
      was considered significant. RESULTS: The mean follow-up after surgery for PC was
      102.4 months and for BC was 103.6 months. At last follow-up, data suggesting
      failure (Stress score >=7, urge score >=7, Pad test with weight < 15 g/day and
      positive MT during lithotomic/upright position) were more frequent in BC group (P
      > 0.05; P > 0.0; P > 0.01; P > 0.05; P > 0.05, respectively). The incidence of
      recurrent SUI was 5.2% after PC and almost triple (14.6%) after BC. Residual
      urine <100 ml and weak stream were more frequent in the BC group (P > 0.05; P >
      0.01, respectively). Detrusor over-activity on urodynamic studies, Flow time <60
      s, urethral pressure profilometry positive for obstruction had a higher incidence
      in BC group (P > 0.01; P > 0.001; P > 0.01, respectively). CONCLUSION: Our
      modified pleated colposuspension showed improved outcomes when compared with
      standard Burch colposuspension.

PMID- 24082434
TI  - Retraction notice.

PMID- 24082435
TI  - Endoscopic treatment of vesicoureteric reflux with dextranomer/hyaluronic acid
      copolymer (Deflux): Single-surgeon experience with 48 ureters.
AB  - PURPOSE: VUR is a common urologic problem in children. Cystoscopic injection of
      bulking agents (most commonly Deflux) has gained popularity as the first line
      treatment in the west. However, primarily due to cost factors, it has not gained
      much popularity in our country. We present our initial experience with
      cystoscopic Deflux injection for VUR. MATERIALS AND METHODS: We reviewed our 3-yr
      experience with the use of Dx/HA (Deflux) for correction of VUR in children and
      adolescents. All children were evaluated with Ultrasound, MCUG and DMSA renal
      cortical scan. The indications for surgical correction of VUR included
      breakthrough infections while on antibiotic prophylaxis, persistent high-grade
      VUR beyond 3 yrs of age, and presence of significant renal damage on DMSA at
      diagnosis (in those children presenting with UTI). All children underwent
      cystoscopic Deflux injection using the standard technique of subureteral
      injection (0.4-1 ml per ureter). All children received antibiotic prophylaxis for
      3-6 months after the injection. USG was done at 1 month and MCUG at 3-6 months
      after the injection. RESULTS: 33 patients (48 ureters) underwent cystoscopic
      Deflux injection for correction of VUR. Mean age was 4.5 yrs (1-17 yrs); there
      were 12 boys and 21 girls. Thirteen children had antenatally diagnosed HDN, while
      20 children presented with febrile UTI. All children had primary VUR except one
      child with persistent VUR 4 yrs after PUV fulguration. The VUR was grade 1-2 in
      8, grade 3-4 in 37, and grade 5 in 3 ureters. Every child had at least one ureter
      with dilating reflux (grades 3,4 or 5). When present, low grade VUR (grade 1or 2)
      was always on the contralateral side. Only one child received a 2(nd) injection
      after 6 months. Follow-up MCUG was done in 28 children (41 ureters). Complete
      reflux resolution was achieved in 27 ureters (65%), and the reflux was downgraded
      in 2 (5%). There were no complications of Deflux injection. CONCLUSIONS:
      Endoscopic correction of VUR in children is a safe and effective minimally
      invasive treatment for VUR. It stops or downgrades VUR in 70% of ureters. At
      present, we recommend it as a first-line treatment for grades 1-4 VUR requiring
      surgical management. Cost is the major factor limiting its use in our country.

PMID- 24082436
TI  - DNA fragmentation and apoptosis induced by safranal in human prostate cancer cell
      line.
AB  - OBJECTIVES: Apoptosis, an important mechanism that contributes to cell growth
      reduction, is reported to be induced by Crocus sativus (Saffron) in different
      cancer types. However, limited effort has been made to correlate these effects to
      the active ingredients of saffron. The present study was designed to elucidate
      cytotoxic and apoptosis induction by safranal, the major coloring compound in
      saffron, in a human prostate cancer cell line (PC-3). MATERIALS AND METHODS: PC-3
      and human fetal lung fibroblast (MRC-5) cells were cultured and exposed to
      safranal (5, 10, 15, and 20 MUg/ml). The 3-(4,5-dimethylthiazol-2-yl)-2,5
      diphenyltetrazolium bromide (MTT) assay was performed to assess cytotoxicity. DNA
      fragmentation was assessed by gel electrophoresis. Cells were incubated with
      different concentrations of safranal, and cell morphologic changes and apoptosis
      were determined by the normal inverted microscope, Annexin V, and propidium
      iodide, followed by flow cytometric analysis, respectively. RESULTS: MTT assay
      revealed a remarkable and concentration-dependent cytotoxic effect of safranal on
      PC-3 cells in comparison with non-malignant cell line. The morphologic
      alterations of the cells confirmed the MTT results. The IC50 values against PC-3
      cells were found to be 13.0 ? 0.07 and 6.4 ? 0.09 MUg/ml at 48 and 72 h,
      respectively. Safranal induced an early and late apoptosis in the flow cytometry
      histogram of treated cells, indicating apoptosis is involved in this toxicity.
      DNA analysis revealed typical ladders as early as 48 and 72 h after treatment,
      indicative of apoptosis. CONCLUSIONS: Our preclinical study demonstrated a
      prostate cancer cell line to be highly sensitive to safranal-mediated growth
      inhibition and apoptotic cell death. Although the molecular mechanisms of
      safranal action are not clearly understood, it appears to have potential as a
      therapeutic agent.

PMID- 24082438
TI  - Evaluation of early endoscopic realignment of post-traumatic complete posterior
      urethral rupture.
AB  - INTRODUCTION: to report our experience with 41 patients treated by early
      endoscopic realignment of complete post-traumatic rupture urethra. MATERIALS AND
      METHODS: The study includes patients presented to our institute, between May 2004
      and April 2009, with post-traumatic complete posterior urethral disruption.
      Preoperative retrograde urethrography, voiding cystourethrography and
      abdominopelvic CT were performed to evaluate the urethral defect length, the
      bladder neck competence, the prostate position, and the extent of the pelvic
      hematoma. Within the first week after trauma, antegrade and retrograde
      urethroscopy were performed to identify both urethral ends and insert urethral
      catheter. Patients were followed up by pericatheter retrograde urethrogram
      monthly postoperatively till catheter removal on disappearance of extravasation.
      Retrograde urethrography, voiding cystourethrography and urethroscopy were
      performed 1 month after the removal of the catheter. Follow-up abdominal
      ultrasound and uroflowmetry monthly till 6 months, bimonthly till 1 year, and
      every 3 months thereafter were encouraged. Urinary continence and postoperative
      erectile dysfunction were assessed by direct patient interview. RESULTS: Forty
      one patients in the age group 17-61 years (mean 37.9) were treated. Patients were
      followed up for. CONCLUSIONS: Early endoscopic realignment for complete posterior
      urethral rupture is a feasible technique with no or minimal intraoperative
      complications. The technique is successful as the definitive line of therapy in
      reasonable number of patients and seems to render further future interventions
      for inevitable urethral stricture easier.

PMID- 24082437
TI  - Comparison of three different techniques of extraction in laparoscopic donor
      nephrectomy.
AB  - AIM: We compare the outcome of three different methods of graft extraction after
      a laparoscopic donor nephrectomy. MATERIALS AND METHODS: AFTER A CONVENTIONAL
      FIVE PORT LAPAROSCOPIC DONOR NEPHRECTOMY, SPECIMEN WAS EXTRACTED THROUGH ONE OF
      THREE APPROACHES: 1. Iliac fossa (IF) incision and hand extraction, 2. Midline
      (MD) periumbilical with a lower polar fat stitch incorporating gonadal vein for
      traction while retrieval, and 3. Pfannensteil (PF) with Gel port extraction.
      Estimated blood loss, operating time, warm ischemia time, incision length, pain
      score, analgesic consumption, hospital stay, wound complications, graft
      complications and recipient creatinine at 6 weeks were analyzed. RESULTS: Warm
      ischemia time was significantly reduced in PF group when compared to other
      groups. Length of the incision was less in the MD group compared to other groups.
      Wound complications were significantly less in PF group when compared to other
      groups. Graft extraction complications were significantly high in MD group
      compared to other two groups. CONCLUSION: Based on the results obtained, our
      current method of preference is by Pfannensteil incision. A controlled extraction
      with the use of a hand assist device would be best for donor safety and to avoid
      graft related complications.

PMID- 24082439
TI  - Controversies in endourology.

PMID- 24082440
TI  - Management of 1-2 cm renal stones.
AB  - INTRODUCTION: The preferred treatment of >1cm stone is shockwave lithotripsy
      (SWL), while that of stone <2 cm is percutaneous nephrolithotomy (PCNL), but
      treatment of 1-2 cm renal stones is a controversial issue. We searched the
      literature to present a comprehensive review on this group. MATERIAL AND METHODS:
      Pubmed search of literature was done using the appropriate key words. We
      separately discussed the literature in lower polar and non lower polar stone
      groups. RESULTS: For non lower polar renal stones of 1-2 cm, SWL is preferred
      approach, while for the lower polar stones; literature favors the use of PCNL.
      Retrograde intrarenal surgery (RIRS) is emerging as a promising technique for
      these calculi. CONCLUSIONS: Treatment of renal stone disease depends on stone and
      patient related, as well as on renal anatomical factors. Treatment should be
      individualized according to site of stone and available expertise.

PMID- 24082441
TI  - Extracorporeal shock wave lithotripsy today.
AB  - Even 32 years after its first introduction shockwave lithotripsy (SWL) remains a
      matter of discussion and controversy. Since the first SWL in 1980, millions of
      treatments have been performed worldwide. To this day SWL remains the least
      invasive of all stone treatments and is considered the treatment modality of
      first choice for the majority of urinary stones. Despite the massive scale on
      which SWL is performed in a wide range of indications, complication rate has
      always remained very low and usually limited to minor side effects and
      complications. The introduction of affordable multifunctional lithotripters has
      made SWL available to more and more departments of urology worldwide. Still many
      centers are disappointed with the treatment results and concerned about the
      adverse tissue effects. In this SWL proves to be the victim of its uninvasiveness
      and its apparent ease of practice. Urologists need proper skill and experience;
      however, to adequately administer shockwaves in order to improve outcome. This
      aspect is too often minimized and neglected. Apart from this the power of
      shockwaves often is underestimated by operators of shockwave machines. Basic
      knowledge of the physics of shockwaves could further reduce the already minimal
      adverse tissue effects. Good training and coaching in the administration of
      shockwaves would no doubt lead to a renaissance of SWL with better treatment
      results and minimal adverse tissue effects. 

PMID- 24082442
TI  - The ideal puncture approach for PCNL: Fluoroscopy, ultrasound or endoscopy?
AB  - Percutaneous renal access is a common procedure in urologic practice. The main
      indications are drainage of an obstructed and hydronephrotic kidney and antegrade
      renal access prior to percutaneous renal surgeries such as percutaneous
      nephrolithotomy (PCNL) and percutaneous endopyelotomy (EP). The contraindications
      for this technique are patients with history of allergy to topical or local
      anesthesia and patients with coagulopathy. The creation of a percutaneous tract
      into the renal collecting system is one of the important steps for percutaneous
      renal access. This step usually requires imaging. The advantages and
      disadvantages of each modality of image guidance are controversial. We performed
      a structured review using the terms: Percutaneous nephrostomy, guidance,
      fluoroscopy, ultrasonography, computed tomography (CT) scan, and magnetic
      resonance imaging (MRI). The outcomes are discussed. 

PMID- 24082443
TI  - Current role of microperc in the management of small renal calculi.
AB  - 'Microperc' is a recently described technique in which percutaneous renal access
      and lithotripsy are performed in a single step using a 16 G micropuncture needle.
      'Mini-microperc' is a further technical modification in which an 8 Fr sheath is
      used to allow insertion of ultrasonic or pneumatic lithoclast probe with suction.
      The available evidence indicates that microperc is safe and efficient in the
      management of small renal calculi in adult and pediatric population. It can also
      be used for renal calculi in ectopic kidneys and bladder calculi. The high stone
      clearance rate and lower complication rate associated with microperc make it a
      viable alternative to retrograde intrarenal surgery. 

PMID- 24082444
TI  - Percutaneous nephrolithotomy: Large tube, small tube, tubeless, or totally
      tubeless?
AB  - The role of percutaneous nephrostomy tube for drainage after percutaneous
      nephrolithotomy (PCNL) procedure has come under scrutiny in recent years. The
      procedure has been modified to use of small diameter tubes, 'tubeless' PCNL, and
      even 'totally tubeless' PCNL. A review of the available literature confirms that
      the chosen method of drainage after PCNL has a bearing upon the post-operative
      course. It is generally recognized now that small tubes offer benefit in terms of
      reduced post-operative pain and morbidity. Similarly, nephrostomy-free or
      'tubeless' PCNL, using a double-J stent or ureteric catheter as alternative form
      of drainage, can be used with a favorable outcome in selected patients with the
      advantage of decreased postoperative pain, analgesia requirement, and hospital
      stay. Although the tubeless technique has been applied for extended indications
      as well, the available evidence is insufficient, and needs to be substantiated by
      prospective randomized trials. In addition, 'totally tubeless' approach has also
      been shown to be feasible in selected patients. 

PMID- 24082445
TI  - Management of large prostatic adenoma: Lasers versus bipolar transurethral
      resection of prostate.
AB  - Transurethral resection of prostate (TURP) has long been the most commonly
      performed surgical procedure for the management of benign prostate enlargement
      (BPE), but has several associated limitations. Over the years, laser techniques
      have developed as major contenders as alternative therapies for BPE. However,
      simultaneously, TURP has also flourished and with relatively recent development
      of resection in saline (bipolar TURP), the tussle between laser techniques and
      TURP has further gained momentum. A systematic search was performed on Medline
      using the various Medical subject headings related to the surgical management of
      BPE including TURP, bipolar, lasers, holmium laser enucleation of prostate
      (HoLEP), photo-selective vaporization of prostate (PVP), etc., All articles types
      including meta-analysis randomized controlled trials, review articles, guidelines
      from various urological associations, single center studies from 2002 onward were
      considered for review. Bipolar TURP, HoLEP, and PVP provide equivalent outcomes
      for large prostate adenoma (<60 g). For extremely large glands (<150 g), HoLEP is
      a very efficacious endoscopic alternative to open prostatectomy and has proven
      long-term results over more than a decade. Bipolar TURP and PVP are attractive
      with a minimal learning curves and equivalent short term durability. Surgical
      management of large prostate should be individualized based upon patient's
      comorbidities and surgeon's expertise. 

PMID- 24082446
TI  - Best laser for prostatectomy in the year 2013.
AB  - Lasers have come a long way in the management of benign prostatic hyperplasia.
      Over last nearly two decades, various different lasers have been utilized for
      prostatectomy. Neodymium: yttrium-aluminum-garnet laser that started this
      journey, is no longer used for prostatectomy. Holmium laser can achieve
      transurethral enucleation of the prostatic adenoma producing a fossa that can be
      compared with the fossa after Freyer's prostatectomy. Green light laser has a
      short learning curve, is nearly blood-less with good immediate results. Thulium
      laser is a faster cutting laser while diode laser is a portable laser device.
      Often laser prostatectomy is considered as a replacement for the standard
      transurethral resection of prostate (TURP). To be comparable, laser should reduce
      or avoid the immediate and long-term complications of TURP, especially bleeding
      and need for blood transfusion. It should also be safe in the ever increasing
      patient population on antiplatelet and anticoagulant drugs. We need to take stock
      of the situation and identify, which among the present day lasers has stood the
      test of time. A review of the literature was performed to see if any of these
      lasers could be called the "best laser for prostatectomy in 2013." 

PMID- 24082447
TI  - Controversies in ureteroscopy: Wire, basket, and sheath.
AB  - In the last one to two decades, flexible ureteroscopy has rapidly expanded its
      role in the treatment of urologic stone disease. With the frequent and expanded
      use of flexible ureteroscopy, other ancillary instruments were developed in order
      to ease and facilitate this technique, such as ureteral access sheaths (UAS) and
      a variety of wires and baskets. These developments, along with improved surgeon
      ureteroscopic competence, have often brought into question the need to implement
      the "traditional technique" of flexible ureteroscopy. In this review, we discuss
      a brief history of flexible ureteroscopy, its expanded indications, and the
      controversy surrounding the use of UAS, wires, and baskets. 

PMID- 24082448
TI  - Pyelo-hepatic abscess caused by renal calculi: A rare complication.
AB  - Neglected renal calculi can lead to a variety of complications secondary to
      obstruction and infection. Pyonephrosis arising in this scenario often presents
      as a urological emergency and requires urgent surgical intervention. In rare
      circumstances, when left unaided, the kidney is unable to contain the infection
      and spread of pus may occur into the surrounding spaces like the retroperitoneum
      and the peritoneum. We report a very unusual complication of pyonephrosis leading
      to a hepatic abscess. We believe this is the first reported case of an acute
      renal infection due to stone disease ascending into the liver. 

PMID- 24082449
TI  - Spontaneous closure of urethrovaginal fistula associated with pelvic fracture.
AB  - Female urethral injury following pelvic fracture is a rare entity. Due to the
      absence of large series, management guidelines are still not standardized.
      Patients can have associated urethrovaginal or vesicovaginal fistula, management
      of which poses a major challenge to the reconstructive urologist. Spontaneous
      closure of fistula produced by gynecological or obstetrical injuries have been
      described in the literature. Spontaneous closure of fistula caused due to pelvic
      fracture has not been described in the literature. 

PMID- 24082450
TI  - Pleomorphic undifferentiated sarcoma of urinary bladder with calcified pulmonary
      metastasis: A rare entity.
AB  - We report the case of a 29-year-old male who presented to us with hematuria,
      dysuria and bilateral flank pain. On evaluation, the patient was found to have
      primary pleomorphic undifferentiated sarcoma of bladder with calcified pulmonary
      metastasis, confirmed with computerized tomography scan and immunohistochemistry.

PMID- 24082451
TI  - Microperc for the management of renal calculi in pelvic ectopic kidneys.
AB  - Management of stone disease in an ectopic kidney is challenging. Laparoscopy or
      ultrasound guided percutaneous nephrolithotomy and retrograde intra-renal surgery
      are the preferred techniques for these stones. We performed ultrasound guided
      microperc using a 16 G needle for the management of renal calculi in pelvic
      ectopic kidneys in two patients. There was no intraoperative or post-operative
      complication. Both patients had complete stone clearance and were discharged on
      the first post-operative day. Ultrasound guided microperc is a safe and effective
      option for the management of small renal calculi in pelvic ectopic kidneys. 

PMID- 24082452
TI  - Chylolymphatic cyst of the greater omentum presenting as abdominoscrotal swelling
      in a child.
AB  - Omental cyst are rare abdominal lesions and are difficult to diagnose. They are
      detected incidentally during imaging studies performed for unrelated reasons. In
      children, it may present as an acute abdomen due to intestinal obstruction or
      painless abdominal swelling. Imaging is helpful in excluding other causes of lump
      abdomen. We encountered a case of giant omental cyst presenting with
      abdominoscrotal swelling in a child. The patient underwent laparotomy and the
      diagnosis of omental cyst was established by intraoperative findings. Thus
      complete excision of the cyst was performed. The diagnosis was confirmed by
      pathological examination. 

PMID- 24082453
TI  - A giant ureteric calculus.
AB  - Ureteric stones are usually small and symptomatic. We present a case of a 35-year
      old female who presented with minimally symptomatic right distal ureteric
      calculus with proximal hydroureteronephrosis. Laparoscopic right ureterolithotomy
      was performed and a giant ureteric calculus measuring 11 cm Chi 1.5 cm, weighing
      40 g was retrieved. 

PMID- 24082454
TI  - No preanalytical errors in laboratory testing: a beneficial aspect for patients.

PMID- 24082456
TI  - Association between urinary IgG and relative risk for factors affecting
      proteinuria in type 2 diabetic patients.
AB  - Abnormal glomerular permeability is the primary step towards the
      glomerulosclerosis. The progression rate of glomerulosclerosis is proportionate
      to abundance and severity of lesions created at incipient stage, which is
      reflected as proteinuria even though eGFR remains in the normal range. Therefore,
      there is a current need to find out the association between relative risks for
      the factors leading to proteinuria. The relations could be more informative, if
      it is with respect to the macromolecules like "IgG" excretion in urine. Type 2
      diabetic patients were selected for this study with eGFR > 75 ml/min/1.73 m(2)
      and grouped into four quartiles based on UIgGCR. The markers of key factors
      affecting progression of proteinuria were estimated through biochemical tests.
      The impact of these markers on proteinuria was accessed by applying multinomial
      logistic regression. The adjusted odds ratio for the UGAGCR was 1.186 (95 % CI:
      1.061-1.327) P < 0.003 in highest quartiles of UIgGCR, followed by odds ratio for
      markers of collagen catabolism 1.051 (95 % CI: 1.025-1.079) P < 0.001, and USACR
      1.044 (95 % CI: 1.013-1.077) P < 0.006 respectively. The marker of glycation,
      i.e., glycated hemoglobin showed the highest odds ratio 5.449 (95 % CI: 1.132
      26.236) P < 0.035. In addition, odds for the systolic blood pressure was observed
      1.387 (95 % CI: 1.124-1.712) P < 0.002. The higher odds inform and could help to
      discriminate the diabetic patients with fast progressive diabetic nephropathy.
      The study describes critical relationship between the urinary excretion of IgG
      and factors leading to proteinuria in type 2 diabetic patients. 

PMID- 24082455
TI  - Non transferrin bound iron: nature, manifestations and analytical approaches for
      estimation.
AB  - Iron is an essential trace element and plays a number of vital roles in
      biological system. It also leads the chains of pathological actions if present in
      excess and/or present in free form. Major portion of iron in circulation is
      associated with transferrin, a classical iron transporter, which prevent the
      existence of free iron. The fraction of iron which is free of transferrin is
      known as "non transferrin bound iron". Along with the incidence in iron over
      loaded patient non transferrin bound iron has been indicated in patients without
      iron overload. It has been suggested as cause as well as consequence in a number
      of pathological conditions. The major organs influenced by iron toxicity are
      heart, pancreas, kidney, organs involved in hematopoiesis etc. The most commonly
      suggested way for iron mediated pathogenesis is through increased oxidative
      stress and their secondary effects. Generation of free oxygen radicals by iron
      has been well documented in Fenton chemistry and Haber-Weiss reaction. Non
      transferrin bound iron has obvious chance to generate the free reactive radicals
      as it is not been shielded by the protective carrier protein apo transferrin. The
      nature of non transferrin bound iron is not clear at present time but it is
      definitely a group of heterogenous iron forms free from transferrin and ferritin.
      A variety of analytical approaches like colorimetry, chromatography, fluorimetry
      etc. have been experimented in different research laboratories for estimation of
      non transferrin bound iron. However the universally accepted gold standard method
      which can be operated in pathological laboratories is still to be developed. 

PMID- 24082457
TI  - Lack of Circadian Pattern of Serum TNF-alpha and IL-6 in Patients with
      Fibromyalgia Syndrome.
AB  - The present study was designed to test the hypothesis of a circadian variation in
      circulating levels of tumor necrosis factor-alpha (TNF-alpha) and interleukin-6
      (IL-6) in women with fibromyalgia syndrome (FMS). Serum levels of IL-6 and TNF
      alpha were measured at 4 h intervals of the day in 50 women with FMS satisfying
      American College of Rheumatology criteria for FMS (age 36.68 +/- 9.89) as well as
      50 healthy control women (age 32.82 +/- 10.53). Serum TNF-alpha levels were
      substantially increased in patients with FMS but showed no circadian variation.
      In contrast, no difference in the levels of IL-6 was found. Moreover, there was
      also no circadian variation in both the groups of patients and controls. We
      conclude that no circadian pattern exists in the circulating levels of serum IL-6
      and TNF-alpha in patients with FMS, although TNF-alpha levels are found raised in
      patients with FMS. 

PMID- 24082459
TI  - Hydro-Alcoholic Cinnamon Extract, Enhances Glucose Transporter Isotype-4
      Translocation from Intracellular Compartments into the Cytoplasmic Membrane of
      C2C12 Myotubes.
AB  - Cinnamon has been used as an anti-diabetic agent for centuries but only in recent
      few years its mechanism of action has been under investigation. Previous studies
      showed that cinnamon might exert its anti-diabetic effect via increasing glucose
      transporter isotype-4 (GLUT4) gene and glycoprotein contents in fat cells. To
      study if hydro-alcoholic cinnamon extract (HACE) enhances GLUT4 translocation
      from intracellular compartments of nuclear or endoplasmic reticulum membranes
      (N/ER) into the cytoplasmic membrane (CM). C2C12 myoblastic cell line were seeded
      in DMEM plus 20 % FBS and differentiated to myotubes using 2 % horse serum. After
      myotubes formation, 100 or 1,000 MUg/ml HACE, as intervention, and as control 1 %
      DMSO were added for 3 h. Cells were washed and homogenized followed by
      ultracentrifuge fractionation, protein separation by SDS-PAGE and GLUT4 detection
      using semi-quantitative Western blotting. Data analysis was done by two
      independent samples t test for comparison of mean +/- SD of GLUT4 percent in
      categories. GLUT4 contents were higher in CM of groups 100 and 1,000 MUg/ml HACE
      and lower in 1 % DMSO treated myotubes (CI = 0.95, P < 0.05). For N/ER reverse
      results were obtained (CI = 0.95, P < 0.05). As our results have shown HACE
      induces GLUT4 translocation from intra-cell into cell surface. We conclude that
      cinnamon maybe a choice of type-2 diabetes mellitus treatment because its extract
      enhances GLUT4 contents in CM where it facilitates glucose entrance into the
      cell. However it is necessary to trace the signaling pathways which are activated
      by HACE in muscular tissue. 

PMID- 24082458
TI  - Does HCV Patients Who Have BCL2 43Ala Genotype and Normal GH1 Levels Can Achieve
      Response to IFN Based Therapy?
AB  - The main objective of the current study is to examine the role of the statistical
      relation between BCL2 gene (Ala43Thr) single nucleotide polymorphism and growth
      hormone (GH1) levels in Egyptian HCV genotype-4 patients before and after
      treatment with pegylated interferon plus ribavirin. Eighty patients with HCV
      genotype-4 and 40 healthy volunteers as controls were enrolled in the prospective
      study. Gene polymorphism of BCL2 (Ala43Thr) using PCR-RFLP technique and GH1
      concentrations using ELISA procedure were measured for all patients and controls.
      The present study resulted that Responder HCV genotype-4 Patients, with BCL2
      43Ala genotype, have high significant increase in pre-treatment GH1 levels (>1
      ng/ml); which represent normal levels, as compared to non-responders pre
      treatment GH1 levels (<1 ng/ml); which represent low concentrations. We concluded
      that HCV genotype-4 patients who have normal GH1 concentrations and BCL-2 43Ala
      genotype can successfully achieve response to interferon based therapy. 

PMID- 24082460
TI  - Antarctic Harsh Environment as Natural Stress Model: Impact on Salivary
      Immunoglobulins, Transforming Growth Factor-beta and Cortisol Level.
AB  - The Antarctic continent on the planet Earth is full of environmental extremes. It
      is considered as natural stress model. Therefore, the present study examined the
      effect of harsh environment on the certain salivary markers of 28th Indian
      Antarctic expeditioners. Thirty healthy men and women (median age 36 year; range
      22-61 year) participated in this study. Parameters measured were salivary IgA
      (SIgA), IgM (SIgM), TGF-beta and cortisol level at three different time points:
      (I) before leaving India on 26th October 2008 for base line level; (II) after 1
      month on-board journey on 31st January 2009 in Southern Ocean and (III) after 1
      month staying at Maitri, Antarctica on 3rd March 2009. Our observation indicated
      that Ship borne journey and Antarctic environment increased the SIgA levels while
      that of SIgM level was not altered on-board but decreased by staying for 1 month
      at Antarctica. No significant alteration was found in the TGF-beta and cortisol
      level at any point of time. The present study concluded that ship borne journey
      and Antarctic environment may induce the SIgA level while SIgM level decreased in
      environmental extremes of Antarctica. 

PMID- 24082461
TI  - Dyslipidemia associated with poor glycemic control in type 2 diabetes mellitus
      and the protective effect of metformin supplementation.
AB  - The nature of the dyslipidemia associated with diabetes mellitus is complex and
      is the major risk factor for atherosclerosis and coronary artery disease. Aim of
      this study was to assess the effect of glycemic control, achieved by metformin,
      glibenclamide and insulin, on lipid profile in type 2 diabetic patients. One
      hundred and sixty-five type 2 diabetes mellitus patients were classified into
      good glycemic control (Group I) and poor glycemic control (Group II) on the basis
      of their blood HbA1c values. The Group II was characterized with high serum
      triglyceride (190.46 +/- 15.20 mg/dl), total cholesterol (175.3 +/- 6.31 mg/dl)
      as well as high LDL-cholesterol (109.0 +/- 5.88 mg/dl). Significant correlations
      were evident between HbA1c and dyslipidemia, particularly serum TG (r = 0.28, P <
      0.05), and between HbA1c and total cholesterol (r = 0.310, P < 0.05). Better
      glycemic control and improved dyslipidemia were observed in patients on
      combination therapy of metformin plus glibenclamide. 

PMID- 24082462
TI  - Emerging Trend of Mutation Profile of rpoB Gene in MDR Tuberculosis, North India.
AB  - The present study was conducted on North Indian population to observe rpoB gene
      mutation profile in multidrug resistant Mycobacterium tuberculosis. This was an
      observational study. 30 cases of MDR-TB proven by culture and drug sensitivity
      were selected. DNA sequencing of 81 bp (codon 507-533) long RRDR of Mycobacterium
      tuberculosis was done to detect the sites of mutation. Out of 30 cases, 24 showed
      a single mutation in the RRDR region of rpoB gene in which 16 (53.33 %) showed
      mutation in codon 531(TCG->TTG), 5 cases (16.66 %) showed mutation in codon
      526(CAC->TAC), mutation in codon 516(GAC->GTC, AAC) was present in 3 cases (10
      %). It was also observed that mutation in more than one codon was present in 4
      cases (13.33 %), which included deletion at codon 509(AGC->-GC), mutation at
      513(CAA->CTA), 516, 526, 529(CGA->CTA) and 531. No mutation was detected in RRDR
      in 2 cases (6.66 %). Our finding of 13.33 % cases with multiple sites of mutation
      in RRDR region is in contrast to earlier studies done in North India which showed
      single mutation detected in RRDR of rpoB gene that highlights the emerging change
      in the trend of mutation profile of rpoB gene in rifampicin resistant
      Mycobacterium tuberculosis. 

PMID- 24082463
TI  - Prostate specific antigen in cord blood.
AB  - Recent studies have demonstrated the presence of prostate specific antigen (PSA)
      in cord blood of male as well as female babies. The placental progesterone and
      estradiol up-regulate the synthesis and secretion of PSA in Placenta. This PSA is
      presumed to play a role in intrauterine growth of fetus by virtue of its
      proteolytic action on several substrates including insulin-like-growth-factor
      binding-protein-3, insulin chains and Interleukin-2. This study was planned with
      the objective of correlating the levels of PSA in cord blood to gestation at
      delivery, the type of delivery and gender of the fetus. Fifty-seven cord blood
      samples were collected from the umbilical cord during delivery or mid-trimester
      abortion and analyzed for PSA using 'Active PSA DSL-9700 ultra sensitive' kit
      employing two-site immuno-radiometric assay principle and having a detection
      limit of 0.001 ng/ml. Mean PSA levels in cord blood were found to be 0.112 +/-
      0.027 ng/ml. The concentration of PSA in cord blood was found to be higher in
      case of higher gestational age, male baby and operative delivery. 50 % of cord
      bloods for female babies had PSA below detection limit (range <0.001-0.460
      ng/ml), while all the male samples had detectable PSA (range 0.11-0.973 ng/ml).
      Higher Progesterone levels found in prenatal maternal blood in case of male
      babies may be responsible for the higher cord blood PSA. Mean cord blood PSA was
      0.150 +/- 0.150 ng/ml in forceps delivery and 0.078 +/- 0.012 ng/ml in normal
      vaginal delivery. Forceps delivery causes much more stress and strain as compared
      to a normal vaginal delivery, resulting in increased levels of adrenal
      glucocorticoids, and therefore, higher cord blood PSA. 

PMID- 24082464
TI  - Role of Heme Oxygenase, Leptin, Coenzyme Q10 and Trace Elements in Pre-eclamptic
      Women.
AB  - The objective of this study to evaluate heme oxygenase (COHb), leptin and
      coenzyme Q10 (CoQ10) in pre-eclamptic women. Also Zinc, copper, Iron, total iron
      binding capacity, Ferritin and uric acid were assessed. 120 female subjects were
      included in this study. They were divided into, 60 female with normal pregnancy
      attending the outpatient clinic, 60 pre-eclamptic patients were recruited from
      obstetrics and gynaecology department El-kasr El-Aini hospital. The results
      showed that in pre-eclampatic group, leptin level was significantly increased
      while COHb and CoQ10 was significantly decreased. It is concluded that
      hemeoxygenase, leptin and coenzyme CoQ10 can be considered as new markers for
      prediction of pre-eclampsia. 

PMID- 24082465
TI  - Evaluation of oxidative stress and DNA damage in benign prostatic hyperplasia
      patients and comparison with controls.
AB  - In the present study, oxidative stress and lymphocytic DNA damage in both pre-op
      and post-op benign prostrate hyperplasia (BPH) patients with age >50 years was
      evaluated and compared with normal healthy subjects (controls- without any
      evidence of disease) of the same sex and age group. From December 2007 to
      November 2009, oxidative stress in 45 BPH patients were evaluated both before
      (pre-op patients) and after 7 days of surgery (post-op patients) in terms of
      measurements of plasma levels of (1) various anti-oxidative enzymes, (2) non
      enzymatic antioxidants and (3) malondialdehyde which is a product of lipid
      peroxidation. The lymphocyte DNA damage was also evaluated by single cell
      alkaline gel electrophoresis in terms of tail length migration in these patients.
      These values were compared with their respective control subjects of similar sex
      and age group. The activities of antioxidant enzymes and the levels of
      antioxidant, reduced glutathione were found significantly decreased (p < 0.05) in
      serum samples of pre-operative group of BPH patients as compared to the controls.
      These altered parameters increased significantly (p < 0.05) and returned to their
      near normal control values, but not up to baseline values, in post operative
      patients i.e. after the cancer load was decreased by surgery. Lymphocytic DNA
      damage was found to be significantly increased in pre-op group as compared to
      controls and was reduced after surgery in post-op group. The present study
      therefore, shows significantly increased levels of oxidative stress and DNA
      damage in BPH patients which were reduced after removal of tumour load. Thus
      oxidative damage plays an important role in prostate tumourogenesis and timely
      management of oxidative stress can be of importance in preventing the occurrence
      of BPH. 

PMID- 24082466
TI  - The Prevalence Of beta-Thalassemia Mutations in South Western Maharashtra.
AB  - Thalassemia has been recognized by the World Health Organization as important
      inherited disorders principally impacting on the populations of low income
      countries. In this report, the prevalence of common beta-thalassemia mutations in
      India was defined in 126 beta-thalassemia carrier subjects in a western Indian
      population mainly from the south-western Maharashtra. The six most common beta
      thalassemia mutations were detected, which included IVS I-5 (G-C), IVS I-1 (G-T),
      codon 8-9 (+G), codon 41/42 (-TCTT), Codon 15 (G-A), and 619 bp deletion at 3'
      end of beta-globin gene. These mutations accounted for 93.66 % in 126 beta
      thalassemia carrier subjects and 6.34 % remained uncharacterized. Out of 126, 82
      (65.07 %) showed the most common (prevalent) type of mutation, IVS I-5 (G-C),
      followed by IVS I-1 (G-T) showed by 12 (9.52 %) subjects. Three (2.38 %) subjects
      showed 619 bp deletion, codon 8/9 (+G) and codon 15 (G-A) mutations were present
      in eight subjects each (6.34 %). Only five (3.96 %) subjects showed codon 41/42 (
      TCTT). There were eight (6.34 %) subjects where mutation was not any of the six
      mutations studied. This study provides the pattern of beta thalassemia mutations
      from south-western Maharashtra, which will help to prevent beta-thalassemia using
      prenatal diagnosis and proper counseling. 

PMID- 24082467
TI  - Association of Inflammatory Biomarker C-Reactive Protein, Lipid Peroxidation and
      Antioxidant Capacity Marker with HbF Level in Sickle Cell Disease Patients from
      Chattisgarh.
AB  - This study was undertaken to determine the association of inflammatory biomarker,
      oxidative stress and antioxidant capacity marker with fetal haemoglobin (HbF)
      level among sickle cell trait and sickle cell disease (SCD) patients in
      Chattisgarh. The study group consisted of 51 SCD (SS) patients with painful
      episode, 49 SCD (SS) patients with steady state, 50 sickle cell trait (AS) and 50
      controls. Malondialdehyde (MDA), CRP, total antioxidant power (FARP), total thiol
      and HbF levels were quantified. We found a significant positive (p < 0.0001)
      association between CRP and MDA levels and its inverse association with HbF level
      in SS patients. We also observed that antioxidant capacity had significantly
      positively (p < 0.0001) associated with HbF level. The protective effect of HbF
      was found, because the increase in HbF levels resulted in decrease in lipid
      peroxidation and inflammation in SCD patients. A decrease in the HbF level and
      its antioxidant capacity has been associated with the pathogenesis of SCD. These
      finding may explain the high level of HbF is ameliorating oxidative stress and
      inflammation in SCD patients. 

PMID- 24082468
TI  - Age-Related Changes of Serum Soluble Interleukin 9 Receptor (sIL-9Ralpha) in
      Healthy Subjects.
AB  - Most cytokine receptors including interleukin (IL)-9 have soluble counterparts in
      body fluids. We planned to investigate the pathophysiological significance of the
      serum soluble IL-9 receptor (sIL-9R) level. We determined the serum sIL-9Ralpha
      chain (sIL-9Ralpha) levels in 96 healthy Japanese individuals to establish a
      control value by means of specific human sIL-9Ralpha ELISA, followed by a
      preliminary application in a patient with diarrhea positive hemolytic uremic
      syndrome. Age was negatively correlated with the sIL-9Ralpha level (Spearman r = 
      0.241, n = 96, p = 0.0180). The serum sIL-9Ralpha level showed a progressive
      decline to the normal adult level by the age of 30. The serum sIL-9Ralpha level
      of the patient with HUS was markedly higher than those of the age-matched control
      from the onset of the disease. Because of the remarkable age-dependent
      variability of sIL-9Ralpha in healthy subjects, disease-related changes, as well
      as therapy-dependent alterations, should be considered with caution. Thus, it is
      recommended that when the serum sIL-9Ralpha levels of patients are evaluated, the
      values should be compared with those of age-matched controls. The established
      control value will be used to discriminate between normal and the pathological
      conditions in our future studies. 

PMID- 24082469
TI  - Temporal trends of malondialdehyde in stored human plasma.
AB  - Malondialdehyde (MDA) is widely used as oxidative stress biomarker in biomedical
      research. Plasma is stored in deep freezers generally till analysis. Effect of
      such storage on MDA values, which may be variable and prolong, was incidentally
      observed in the ongoing study which is to estimate oxidative stress with oral
      iron. Plasma from blood samples of pregnant women (20-30 years age) in third
      trimester of singleton pregnancy (n = 139), consuming oral iron tablets was
      stored at -20  degrees C with intention of MDA estimation, as soon as possible.
      However logistic problems led this storage for prolonged and variable period (1
      708 days). When values of MDA estimated using "Ohkawa" 79 method and readings
      were plotted against time to check the temporal effect, it showed a hyperbolic
      curve. Standard deviation (SD) was lowest when samples were tested within 3 weeks
      time. The samples analyzed within 3 weeks had mean +/- SD value of 31.59 +/-
      26.11 MUmol/L, while 123.7 +/- 93.97 and 366.5 +/- 189.8 MUmol/L for samples
      stored for 1-3 and 4 months to 1 year respectively. Mean +/- SD were 539.9 +/-
      196.8 in the samples store for more than a year. Rate of change in values was
      also lowest (0.0433 MUmol/L/day) in the samples tested within first 3 weeks,
      which rose to 1.2 MUmol/L/day during 3 month's storage. This rate peaked at
      storage of 120 days (1.87 MUmol/L/day) and fell to 0.502 MUmol/L/day in the
      second year of storage. It is concluded that at -20  degrees C, only 3 weeks of
      storage time should be considered valid for fairly acceptable stability in MDA
      values. 

PMID- 24082470
TI  - Assessment of oxidative stress and inflammatory process in patients of multiple
      myeloma.
AB  - Multiple myeloma is a disseminated malignancy of monoclonal plasma cells that
      accounts for 15 % of all hematological cancers. The present study was conducted
      to evaluate the role of inflammation and oxidant-antioxidant dynamics in the
      etiology of this disease. The study population comprised of 20 cases of multiple
      myeloma and 20 healthy controls. The parameters evaluated were serum
      malondialdehyde (MDA), superoxide dismutase (SOD) and ferritin levels. The serum
      MDA levels were 1.9 +/- 0.96 nmol/ml in cases as compared to 0.98 +/- 0.55
      nmol/ml in the controls. Similarly, a statistically significant difference was
      noted in the SOD and ferritin levels between the cases and controls (93.2 +/-
      23.8 vs. 210.1 +/- 190.5 U/ml and 285.8 +/- 216.4 vs. 131.8 +/- 30.1 ng/ml
      respectively). Our study highlights the imbalance in the oxidant-anti oxidant
      mechanism and the role of smoldering inflammation in the etiology of multiple
      myeloma. 

PMID- 24082471
TI  - Identification of a Rare Hemoglobin Variant HbJ-Rajappen [alpha90 (FG2) Lys ->
      Thr] Using Mass Spectrometry.
AB  - Hemoglobin J-Rajappen (alpha)90 Lys -> Thr is an alpha chain variant found in
      heterozygous state and presents normal hematological blood picture. Due to the
      ambiguity in results obtained while analyzing by HPLC and alkaline gel
      electrophoresis, we report this rare case of HbJ-Rajappen using non denaturing
      gel electrophoresis and matrix assisted laser desorption ionization mass
      spectrometry. Though HbJ-Rajappen has earlier been reported using different
      techniques, this is the first report being validated using mass spectrometry
      technique. 

PMID- 24082472
TI  - Diagnosis of Sanfilippo disease correlating clinical, radiological and
      biochemical findings-a case report.
AB  - Mucopolysaccharidoses (MPS) are a group of genetic diseases and its diagnosis is
      a challenging task due to multiple differential diagnosis. We had combined
      clinical findings, radiological and ophthalmological features. Biochemical test
      for urine glycosaminoglycans (GAG) was done for confirmation of diagnosis in the
      patient. The case of Sanfilippo disease was characterized by slowly progressive,
      severe CNS involvement with mild somatic disease. Radiological features were
      suggestive of Sanfilippo disease and urine GAG test for MPS was positive in the
      case. With the clinical features we had multiple differential diagnoses. The
      radiological investigations minimized the list and the biochemical test confirmed
      GAG in urine. In this case the combination of clinical, radiological and
      biochemical findings confirmed the diagnosis of Sanfilippo disease. 

PMID- 24082474
TI  - The sway of interventions today....

PMID- 24082473
TI  - A review on the article: role of common biochemical markers for the assessment of
      fracture union.
AB  - Criterion for patient selection and demographic comparison between the two
      groups, the numbers in individual groups (normal union or defective union) how
      the observers were blinded for the samples and control group measurements in the
      graphs were not mentioned. No data on actual measurement levels is given. No
      where it is mentioned like it is an average of all normal union or defective
      union in tables or diagrams. The treatment methodology maybe still focused
      including either conservative or surgical treatment since a displaced fracture
      cannot be compared with an osteotomy. The cases shall be followed up for a longer
      period. Some suggestions on how to blind the observers is given. In the one year
      period there was neither mention of the failure of treatment or complications of
      any of neither these 36 cases nor any drop out for follow-ups. There was also no
      mention of any case which initially put on conservation was changed to surgical
      management. The authors could have one group of patients taking this food stuff
      and another group who refused this food stuff. The statistical test used to
      compare the levels of factor is not mentioned. Mere statement that 'p' values
      were significant will not benefit the reader. Failure to produce X-rays even for
      a single case weakens the study. X-rays are needed to confirm the diagnosis of a
      fracture and confirm the position of implants and fracture fragments. The
      remaining period after confirming the fracture/implant position the case shall be
      followed only with marker estimation. Once the desired levels of increase or
      tapering of marker level achieved then X-rays can be taken to correlate with
      clinical findings and radiology. Union as one group and the second group shall be
      called as non-union or delayed union. The second group (the poor callus group) is
      mentioned as malunion possibly by over-sight. Probably they were meaning the non
      union or delayed union group or defective union as malunion. This should be
      preferably be written non union or delayed union. Malunion means the fracture
      actually unites and union process is completed. In a group of fractures
      (hypertrophic non unions) the callus formation is excessive, still the fracture
      is ununited. Thus the enzyme or markers alone cannot disclose the details of the
      completion of union they can herald bone formation. 

PMID- 24082475
TI  - Image-guided chemoport insertion by interventional radiologists: A single-center
      experience on periprocedural complications.
AB  - PURPOSE: To report our early experience in image-guided chemoport insertions by
      interventional radiologists. MATERIALS AND METHODS: This was a cross-sectional
      study conducted in a tertiary center with 161 chemoport insertions done from June
      2008 to June 2010. The chemoports were inserted either at the angiography suite
      or at the mobile operation theater unit. Ninety percent of the chemoports had
      right internal jugular vein (IJV) as the entry site. Other entry sites included
      the left IJV, subclavian veins and the inferior vena cava. Immediate and early
      complications were recorded. All insertions were performed under image guidance
      with the aid of ultrasound and fluoroscopy. RESULTS: The technical success rate
      was 99.4%. In terms of immediate complications, there were only two cases of
      arterial puncture that resolved with local compression. No pneumothorax or air
      embolism was documented. Twenty-six early complications were recorded. The most
      common early complication was catheter blockage (12/161; 7.4%), followed by
      catheter-related infection (9/161; 5.6%). Other complications were catheter
      malposition, venous thrombosis and catheter dislodgement or leak. A total of 11
      (6.8%) chemoports had to be removed within 30 days; most of them were due to
      infections that failed to respond to systemic antibiotic therapy. In terms of
      place of procedure, there were no significant differences in complication rates
      between the angiography suite and the mobile operation theater unit. CONCLUSION:
      Image-guided chemoport insertion by interventional radiologist gives low
      periprocedural complication rates. Using right IJV as the entry site, the image
      guidance gives good success rate with least complication.

PMID- 24082476
TI  - Endovascular treatment of hepatocellular carcinoma with drug eluting
      microparticles (DC-Beads): CT evaluation of response to the treatment.
AB  - BACKGROUND AND STUDY AIMS: Our aim was to assess the efficacy and tolerability of
      drug-eluting beads-transarterial chemoembolization (DEB-TACE) in the treatment of
      hepatocellular carcinoma (HCC), evaluating the response to the treatment after 1,
      6, 12, and 24 months with multidetector computed tomography (MDCT) comparing
      European Association for the study of the Liver (EASL) and modified Response
      Evaluation Criteria in Solid Tumors (mRECIST) criteria. MATERIALS AND METHODS: We
      enrolled 154 patients with uni- or multifocal HCC who underwent a DEB-TACE. A
      total of 278 HCC nodules were treated. CT follow-up was performed at 1, 6, 12,
      and 24 months after the procedure according to the EASL and RECIST criteria
      evaluating overall target and target nodule response. We also analyzed the
      shrinking of nodules in relation to response to treatment. RESULTS: A total of
      278 nodules of HCC underwent TACE by using DC-Beads: At 24, months complete
      response was similar for EASL and RECIST criteria (112 vs. 121 nodules) with
      optimal accordance between methods and readers with k = 0.9. Partial Response
      resulted significantly different among the two methods within the first month,
      otherwise was similar after 24-month follow-up. Similar results in both methods
      were found for nodules classified as Stable Disease (P > 0.05). Progressive
      Disease results were similar in both the groups according to both the
      classification criteria without any significant difference (P > 0.05).
      CONCLUSION: Our study confirmed that EASL and mRECIST criteria are both effective
      methods for patient follow-up, however with some technical differences.

PMID- 24082477
TI  - Initial experience with AngiosealTM: Safety and efficacy of the endovascular
      closure device.
AB  - BACKGROUND: Vascular access site management is crucial to safe, efficient, and
      comfortable diagnostic or interventional percutaneous procedures. The AngiosealTM
      vascular closure device has been shown to be safe and effective in reducing the
      time to hemostasis following angiographic or interventional procedures.
      Relatively few studies have been conducted in the UK to assess the safety and
      efficacy of the device in a local setting. MATERIALS AND METHODS: Data were
      retrospectively reviewed on 147 patients who underwent either diagnostic
      angiography or percutaneous interventional procedures from January 2008 to
      October 2009, and who had the femoral access site closed by 6F VIP Angioseal. A
      total of 147 patients (F: 49, M: 98), including 80 right femoral punctures, 57
      left femoral punctures, and 10 bilateral punctures were reviewed using
      radiological reports and patients' clinical data. Data on antiplatelet and
      anticoagulant therapy were recorded. All procedures were carried out by two
      interventional radiologists at a single institution, under similar operating
      conditions. RESULTS: There were a total of six complications (4.47%), of which
      one was a major complication (0.75%), i.e., retroperitoneal bleed. There were
      five minor complications (3.73%), which included device deployment failure (2),
      device malfunction (2), and a superficial hematoma (>6 cm). Total complications
      were 6 out of 157 (3.8%) [95% CI = 0.8-6.8%)]. Successful hemostasis was achieved
      in less than 5 min in over 97% of patients. Successful device deployment was seen
      in over 98% of cases. CONCLUSION: We conclude that in our experience, the
      Angioseal vascular closure device is a safe and efficient means of achieving
      hemostasis post antegrade or retrograde puncture for diagnostic and percutaneous
      intervention procedures.

PMID- 24082478
TI  - Role of radiofrequency ablation in unresectable hepatocellular carcinoma: An
      Indian experience.
AB  - AIMS: To evaluate the role of radiofrequency ablation (RFA) as an ablative
      technique in patients with unresectable hepatocellular carcinoma (HCC). SETTINGS
      AND DESIGN: A tertiary care center, prospective study. MATERIALS AND METHODS: The
      subjects comprised 31 patients (30 males, one female; age range 32-75 years) with
      HCC (41 lesions) who were treated with image-guided RFA. The follow-up period
      ranged from 3 months to 6 years, and included a multiphasic computed tomography
      (CT) at 1, 3 and 6 months post-RFA, and every 6 months thereafter. Patient
      outcome was evaluated and the tumor recurrence, survival and complications were
      assessed. STATISTICAL ANALYSIS USED: Discrete categorical data were presented as
      n (%) and continuous data as mean +/- SD. Pearson correlation coefficient was
      used to determine the relationship between the different variables. Kaplan-Meier
      survival curve and Log-rank test were used to test the significance of difference
      between the survival time of the different groups. RESULTS: The ablation success
      rate was 80.5% (33/41 HCC lesions). 12.2% (5/41) of the lesions were managed with
      repeat RFA due to tumor residue. 4.9% (2/41) of the lesions were managed with
      repeated RFA and transarterial chemoembolization. Eight patients had tumor
      recurrence (five patients (16.1%) had local recurrence and three patients (9.6%)
      had distant recurrence). Eleven patients died within 3.5-20 months post-RFA. The
      survival rate at 1 year in patients who completed at least 1 year of follow-up
      was 63.3%. There was one major complication (1/31, 3.2%) in a patient with a
      subcapsular lesion and ascites. This patient developed hemoperitoneum in the
      immediate postprocedure period and was managed with endovascular treatment. She,
      however, had hepatic decompensation and died 48 h post-RFA. CONCLUSION: RFA is an
      effective and safe treatment for small unresectable HCC.

PMID- 24082479
TI  - Giant sacrococcygeal teratoma embolization.
AB  - Resection of giant sacrococcygeal teratoma with high-vasculature in newborns can
      be a fatal procedure due to massive bleeding of the tumor. Endovascular
      embolization of the arteries that supply the tumor may lead to minimal blood
      loss. We present a case of giant high-vascular sacrococcygeal teratoma type-1
      that was embolized in an infant born at 35 weeks gestation. This procedure lead
      to a safe, surgical resection with minimal bleeding: 12 ml. 

PMID- 24082480
TI  - Cystic adventitial disease of popliteal artery with significant stenosis.
AB  - Cystic adventitial disease of popliteal artery is a rare condition of unknown
      etiology which usually presents in middle-aged men. We present Doppler and
      computed tomography angiography findings in a case of cystic adventitial disease
      with significant obstruction of popliteal artery, with secondary narrowing of
      popliteal vein. 

PMID- 24082481
TI  - Embolization of a large high-flow renal arteriovenous fistula using 035" and 018"
      detachable coils.
AB  - Transcatheter embolization of renal arteriovenous fistula (AVF) is a minimally
      invasive procedure that, in some occasions, can replace surgery and potentially
      save the kidney. The embolization techniques for the renal AVFs have evolved
      considerably with the availability of newer hardwares. Still, the risk of
      inadvertent migration of the embolization materials to the pulmonary circulation
      is a concern. This article describes a novel technique of coiling the feeding
      segmental artery to a large high-flow renal AVF using 035" and 018" detachable
      coils only, and briefly reviews the previously described strategies to safely
      embolize renal AVFs. 

PMID- 24082482
TI  - Neuroenteric cysts of the brain-comprehensive magnetic resonance imaging.
AB  - Neuroenteric cysts are developmental cysts that should be differentiated from
      other, more common non-neoplastic cysts as well as cystic neoplasms. While these
      lesions may have varied imaging findings, T1 hyperintense prepontine lesion due
      to mucinous/proteinaceous content is characteristic. Location and imaging
      characteristics aid in formulating the correct diagnosis of
      neuroepithelial/neuroenteric cysts. Magnetic resonance spectroscopy (MRS) has the
      specific finding of N-Acetyl Aspartate (NAA)-like peak at 2.02 ppm which is not
      seen in other cystic lesions. In this study, we aim to discuss the imaging
      findings of these lesions on conventional and advanced MRI findings and provide
      radiologic-pathologic correlation. We also briefly describe the pathogenesis,
      embryology and radiological differential diagnoses of these cysts. 

PMID- 24082483
TI  - Acute Wallerian degeneration of middle cerebellar peduncles due to basilar artery
      thrombosis.
AB  - Wallerian degeneration (WD) is the process of demyelination and disintegration of
      the distal axonal segment following the interruption of the axonal integrity or
      damage to the neuron. We report a patient having WD of middle cerebellar
      peduncles due to pontine infarction caused by basilar artery thrombosis. We
      review the anatomy and discuss the pathogenesis of this condition. 

PMID- 24082484
TI  - Esophagobronchial fistulae: Diagnosis by MDCT with oral contrast swallow
      examination of a benign and a malignant cause.
AB  - We report two cases of esophagobronchial fistulae diagnosed by Multi-detector
      computed tomography (MDCT) oral contrast swallow examination. It is helpful to
      supplement the CT study with an oral contrast swallow as it aids in confirmation
      of a suspected fistula and also demonstrates the fistula tract better. We present
      the clinical details and the imaging findings on MDCT of two cases of
      esophagobronchial fistulae - one secondary to chronic chest tuberculosis and the
      other secondary to a squamous cell carcinoma of the upper esophagus - followed by
      discussion of the etiology, pathogenesis, and imaging of these fistulae. 

PMID- 24082485
TI  - MR enterography in children: Principles, technique, and clinical applications.
AB  - MR enterography is a constantly advancing technique for assessment of bowel with
      newer technology and sequences. It is being increasingly used for the assessment
      of inflammatory bowel disease and has almost replaced barium follow through
      examinations in many institutions. Its lack of radiation makes it an attractive
      alternative for bowel evaluation in children. It has been proved to be highly
      sensitive in the detection of Crohn disease in adults and children. It is also
      superior to barium studies in showing extra-enteric findings and detecting
      complications such as fistulas and abscesses. Even though at present it is almost
      exclusively used for the evaluation of inflammatory bowel disease, it has the
      potential to be used in other conditions affecting the bowel. The principles, MR
      enterography technique pertinent to children, and its utility in the assessment
      of Crohn disease in children are discussed in this review. 

PMID- 24082486
TI  - Sonographic features of agenesis of dorsal pancreas.
AB  - Agenesis of dorsal pancreas is an extremely rare congenital anomaly that occurs
      due to failure of the dorsal pancreatic bud to form the body and tail of the
      pancreas. We report the sonographic appearance of this condition in six cases. 

PMID- 24082487
TI  - The McKusick-Kaufman hydrometrocolpos-polydactyly syndrome: A rare case report.
AB  - A combination of hydrometrocolpos, polydactyly, and cardiac anomlies is the
      cardinal feature of McKusick-Kaufman syndrome. Neonatal hydrometrocolpos is rare
      Mullerian duct anomaly caused by obstruction of the vagina. There is an
      accumulation of mucus secretions proximal to the obstruction. The secretions are
      secondary to intrauterine and postnatal stimulation of uterine and cervical
      glands by maternal estrogens. Here, we report a case of 1-day-old neonate who
      presented with abdominal distension. Ultrasound and computed tomography findings
      revealed a large abdominopelvic cystic mass posterior to the urinary bladder.
      Other associated findings were polydactyly and bilateral hydronephosis.
      Laparotomy confirmed the findings of hydrometrocolpos caused by stenosis/atresia
      of lower vagina. 

PMID- 24082488
TI  - Diffusion-weighted MRI in assessment of renal dysfunction.

PMID- 24082489
TI  - Authors' reply.

PMID- 24082490
TI  - Multiparametric magnetic resonance imaging of prostate cancer.

PMID- 24082492
TI  - Variations of antioxidative responses in two rice cultivars with polyamine
      treatment under salinity stress.
AB  - The rice varieties viz. Nonabokra and Swarna were evaluated on the basis of their
      responses for oxidative stress induced by sodium chloride (NaCl) and the effects
      of exogenously applied polyamine thereon. Rice seedlings were treated with 200 mM
      of NaCl supplemented with two dosages: 1 mM and 2 mM putrescine. Following
      treatments, plants were evaluated for accumulation of reactive oxygen species
      (ROS) like O2 (-), H2O2 etc. in tissues, lipid peroxidation, protein
      carbonylation, accumulation of flavonoids and anthocyanin, activities of
      different oxidative enzymes like guaiacol peroxidase (GPX), catalase (CAT) and
      glutathione reductase (GR). Preliminary, oxidative stress out of salinity was
      ensured by plants from significantly higher accumulation of O2 (-) and H2O2 in
      the tissues of the NaCl treated varieties. Irrespective of varieties, there
      recorded a significant variation of the endogenous polyamine profiles under NaCl
      stress. Interestingly, exogenous application of putrescine had a close
      relationship on O2 (-) and H2O2 content for both the varieties. However,
      Nonabokra was evident as more respondent than Swarna to applied putrescine. The
      other effects of oxidative stress was impacted on plants as higher values of MDA
      content, enhanced rate of protein oxidation and putrescine recorded as an
      alleviating agent regardless of varieties with dose dependant manner. The
      generation of ROS and cellular disintegration was accompanied by up regulation of
      non-enzymatic and enzymatic antioxidation pathways with exogenous application of
      putrescine. For non-enzymatic antioxidant, it revealed that putrescine was highly
      effective for sustaining the anthocyanin and flavonoid content in both the
      varieties under salinity. Whereas, antioxidative enzyme, CAT showed its
      diminished activity; but activity of GPX and GR were significantly induced under
      salinity and it was according to the concentration of applied putrescine. 

PMID- 24082491
TI  - Quantitative RT-PCR analysis of 20 transcription factor genes of MADS, ARF, HAP2,
      MBF and HB families in moisture stressed shoot and root tissues of sorghum.
AB  - Transcription factors (TFs) are an important target in understanding the
      regulation of plant responses to environmental stress including moisture stress.
      Members of the same TF family may differ in their response to moisture stress.
      The expression pattern could vary between shoot and root tissues depending on
      level of moisture stress. A set of five rarely studied TF families viz., MADS-box
      (MCM1, AGAMOUS, DEFICIENS and SRF), Auxin Responsive Factor (ARF), Heme Activator
      Protein 2 (HAP2), Multiprotein Bridging Factor (MBF) and Homeobox (HB) together
      having 20 members in sorghum, were expression analyzed through quantitative real
      time PCR (qRT-PCR) in well watered and moisture stressed shoot and root tissues
      of sorghum using SYBR Green(r) to quantify dsDNA synthesis. Fluorescence values
      were used to calculate PCR efficiency by using LinRegPCR. The PTSb00029.1 and
      PTSb00033.1 of ARF family and PTSb00174.1 and PTSb00175.1 of HB family recorded 2
      to 5, PTSb00221.1 and PTSb00208.1 of MADS family and PTSb00128.1 of HAP2 family
      recorded 5 to 10 fold up-regulation under moisture stress regimes. The
      PTSb00128.1, a HAP2 family member, recorded 15 fold up-regulation in mild
      moisture stressed root tissues. TF genes such as PTSb00218.1, PTSb00220.1,
      PTSb00031.1, PTSb00032.1, PTSb00034.1 and PTSb00223.1 were found down regulating
      in both tissues types under moisture stress condition. However, the PTSb00128.1,
      PTSb00221.1, PTSb00029.1, PTSb00033.1 and PTSb00174.1 TFs were found up
      regulating to varied levels in mild and severe moisture stressed root tissues
      only. Verification of qRT-PCR results was done by in situ hybridization (ISH) of
      randomly selected two TF genes in shoot and root tissues of sorghum. Taken
      together, moisture stress triggered up-regulation of more genes in root tissue
      compared to shoot tissue in sorghum. 

PMID- 24082493
TI  - In vitro screening of potato lines for drought tolerance.
AB  - Fresh water resources are limited and their use in agricultural production is
      expected to come under increasing constraints. Eighteen Syrian lines of potato
      (Solanum tuberosum L.) were screened for drought tolerance by measuring aerial
      and root growth in vitro. Drought stress was evaluated by adding 2, 4, 6, 8 and
      10 % (w:v) of sorbitol to Murashige- Skoog medium and compared to 0 % for the
      control. Water potential of media ranged from -0.58 MPa to -2.5 MPa. Water-stress
      in culture adversely affected plant growth, and genotypes differed for their
      responses. Plant length and stem thickness, leaf area, root number length and
      thickness, and plant fresh and dry weights and plant water content were measured
      and all decreased due to drought. Grouping lines by cluster analysis for response
      to drought resulted in: (1) a tolerant group of six lines, (2) a moderately
      tolerant group of seven lines, and (3) a susceptible group of five lines. The
      variation in germplasm indicated that potato varieties can be developed for
      production under some levels of drought. 

PMID- 24082494
TI  - Impact of water deficit stress on biochemical characteristics of safflower
      cultivars.
AB  - Water deficit stress is one of the severe limitations of crop growth especially
      in arid and semiarid regions of the world as it effect the plant growth at all
      stages of development. In the present study, four safflower genotypes Esfahan
      native, Esfahan-14, PI537,598 and IL111 were tested for their growth and crop
      yield under water-deficit stress. A detailed biochemical analysis was carried out
      at various levels of irrigation to find out the genotypic variation and the
      activity of several enzymes known to play significant role under drought stress.
      A split plot experiment based on randomized complete blocks design was conducted
      at three levels of irrigation: 100 % (normal water requirement for safflower), 75
      % and 50 %. A significant increase in the activity of SOD, CAT, GPX enzymes and
      the levels of ABA and proline was observed with an increase in the water stress
      level in the leaves of all the genotypes investigated. The highest increase in
      the activities of antioxidant enzymes and proline and ABA content with reduced
      electrolyte leakage was observed in the relatively drought tolerance native
      Esfahan cultivar. These results suggest that the cultivars that exhibit highest
      levels of antioxidant enzymes activity and proline and ABA content under water
      deficit conditions may provide better drought tolerance in safflower. 

PMID- 24082495
TI  - Efficacy of putrescine and benzyladenine on photosynthesis and productivity in
      relation to drought tolerance in wheat (Triticum aestivum L.).
AB  - An experiment was conducted to find out the efficacy of putrescine and
      benzyladenine on photosynthesis and productivity in wheat. Seeds of wheat
      genotype HD 2329 (widely adapted under irrigated condition) were grown in ceramic
      pots under standard package and practices. Putrescine (0.1 mM) and benzyladenine
      (0.05 mM) were sprayed on the aerial portion of these plants at the time of
      anthesis. After spray, half of the plants were subjected to water stress by
      withholding irrigation. The non stressed plants were irrigated to keep the soil
      humidity at field capacity. Results showed that drought stress severly reduced
      the photosynthetic attributes, water status and chlorophyll content which were
      significantly improved by foliar application of putrescine/benzyladenine. The
      levels of free proline, amino acids and soluble sugars were higher under water
      stress conditions which were enhanced further by putrescine/benzyladenine.
      Memrane injury was also reduced by both the chemicals. Yield and yield attributes
      reduced under water stress conditions, but putrescine and benzyladenine treated
      plants exhibited significantly higher values over control. Most of these
      parameters were found significantly correlated with grain yield. It is suggested
      that both benyzladenine and putrescine were able to impart drought tolerance in
      wheat but the response of putrescine was more promising owing to better
      management of various physio-biochemical processes, particularly under water
      stress conditions. 

PMID- 24082496
TI  - Proteolytic activities in Phaseolus vulgaris cotyledons under copper stress.
AB  - The changes in the protease activities of bean cotyledons were investigated in
      response to copper stress. Assays using synthetic substrates and specific
      protease inhibitors followed by activity measurements and electrophoresis
      analysis allowed to study the classes of enzymes involved in the storage protein
      mobilization during the germination of bean (Phaseolus vulgaris L) seeds, and
      then identify which ones were affected in the presence of 200 MUM CuCl2 in the
      imbibition medium. Copper treatment affected embryo growth and total protease
      activity. The results of SDS-gelatin-PAGE show that Cu excess led to a decrease
      in protease activity of 45 to 66 kDa. Moreover, cysteine-, aspartic- and metallo
      protease activities were markedly lowered under copper stress, while serine
      protease one was enhanced as well as its activity dependent abundance in
      comparison with control. However, the relative distribution of major cysteine
      protease in H2O-germinated seeds was significantly diminished after Cu exposure.
      Thus, copper excess can disturb the nitrogen freeing from reserve tissues at
      enzymatic level; differential responses of protease classes are discussed,
      notably, cysteine protease in the way of storage protein mobilization and serine
      protease in protective mechanism one. 

PMID- 24082497
TI  - Plant regeneration from immature inflorescence derived callus cultures of salt
      tolerant kallar grass (Leptochloa fusca L.).
AB  - Efficient plant regeneration has been achieved from immature inflorescence
      derived callus cultures of salt tolerant grass Leptochloa fusca (L.). Young
      inflorescence explants displayed wide-ranging responses for callus induction and
      plant regeneration when subjected to different cold treatment durations and
      without cold treatment exposure (control) prior to its inoculation to MS medium
      supplemented with different concentrations/combinations of plant growth
      regulators (PGRs). The PGRs included auxins: 2, 4-dichlorophenoxy acetic acid (2,
      4-D), picloram (Pic), 3, 6-dichloro-2-methoxy benzoic acid (dicamba) and
      cytokinins: Kinetin (KN), N6-benzyl adenine (BA). These treatments promoted
      different callus induction frequencies as well as various callus types such as
      type 1, type 2 and type 3. Induction of type 2 callus (white and compact) with
      potential for regeneration was obtained from cold treated (3 days at 10  degrees
      C) immature inflorescence cultured on MS medium containing 2.0 mg/l dicamba and
      0.25 mg/l BA. The study demonstrated that 2.0 mg/l dicamba and 0.25 mg/l BA
      induced callus promoted improved frequency compared to zilch shoot regeneration
      response with other combinations involving 2, 4-D, picloram, KN and BA. Full
      strength MS supplemented with 2.0 mg/l NAA and 0.5 mg/l BA was found to be
      optimal for plant regeneration. The regeneration frequencies ranged from 13.8 +/-
      1.366 to 55.5 +/- 2.766 with highest number of shoots (19.1 +/- 0.560) per 50-60
      mg of callus as explants after 28 days of inoculation. Plant regeneration was
      also obtained on the dicamba callus induction medium itself within 21 days
      inoculation of immature inflorescence explants. Half strength MS medium both
      semisolid and liquid devoid of plant growth regulators promoted highest frequency
      (92.8 +/- 4.099 and 100 +/- 0.00) of rooting in regenerated shoots. Plants with
      well developed roots were successfully transferred to pots and grown to maturity
      with normal flowering and seed set. This is the first report on induction of
      callus and subsequent plant regeneration in kallar grass using immature
      inflorescence explants. 

PMID- 24082498
TI  - An improved plant regeneration and Agrobacterium - mediated transformation of red
      pepper (Capsicum annuum L.).
AB  - Capsicum annuum (red pepper) is an important spice cum vegetable crop in tropical
      and subtropical countries. Here, we report an effective and reproducible auxin
      free regeneration method for six different red pepper cultivars (ACA-10, Kashi
      Anmol, LCA-235, PBC-535, Pusa Jwala and Supper) using hypocotyl explants and an
      efficient Agrobacterium-mediated transformation protocol. The explants
      (hypocotyls, cotyledonary leaves and leaf discs) collected from axenic seedlings
      of six red pepper cultivars were cultured on either hormone free MS medium or MS
      medium supplemented with BAP alone or in combination with IAA. Inclusion of IAA
      in the regeneration medium resulted in callus formation at the cut ends of
      explants, formation of rosette leaves and ill defined shoot buds. Regeneration of
      shoot buds could be achieved from hypocotyls grown in MS medium supplemented with
      different concentrations of BAP unlike other explants which failed to respond.
      Incorporation of GA3 in shoot elongation medium at 0.5 mg/l concentration
      enhanced the elongation in two cultivars, LCA-235 and Supper, while other
      cultivars showed no significant response. Chilli cultivar, Pusa Jwala was
      transformed with betaC1 ORF of satellite DNA beta molecule associated with Chilli
      leaf curl Joydebpur virus through Agrobacterium tumefaciens. Transgene
      integration in putative transformants was confirmed by PCR and Southern
      hybridization analysis. 

PMID- 24082499
TI  - A simple, novel and high efficiency sap inoculation method to screen for tobacco
      streak virus.
AB  - A rapid and efficient sap inoculation method for tobacco streak virus (TSV) was
      developed in sunflower. Sap from TSV-infected sunflower plants was freshly
      extracted in phosphate buffer and diluted serially from 10(-1) to 10(-8). Two-day
      old seedlings of sunflower were injured at the meristem and immersed in the sap
      for 10 min, maintained at 20  degrees C for 2-3 days and shifted to greenhouse.
      The surviving seedlings in the respective sap dilution were scored for symptoms
      of sunflower necrosis disease (SND). SND symptoms were seen in 80 % of the
      seedlings inoculated with a sap dilution of 10(-5). ELISA and RT-PCR analysis of
      coat protein and movement protein of TSV confirmed SND symptoms. The methodology
      was also found to be reproducible when the sap from the infected plants was
      inoculated onto healthy plants. The main aim of the study was to develop a
      primary screening strategy for the selection of transgenics developed for SND
      resistance. This methodology can also be extended for the analysis of resistance
      against other viruses. 

PMID- 24082500
TI  - Relative expression of CsZCD gene and apocarotenoid biosynthesis during stigma
      development in Crocus sativus L.
AB  - Crocus sativus is a triploid sterile plant characterized by its red stigmas,
      which produce significant quantities of carotenoid derivatives formed from the
      oxidative cleavage of beta-carotene and zeaxanthin. The accumulation of three
      major carotenoid derivatives- crocin, picrocrocin, and safranal- is responsible
      for the color, bitter taste, and aroma of saffron, which is obtained from the
      dried stigma of Crocus. Maximum apocarotenoid accumulation occurs during fully
      developed scarlet stage of stigma development. Zeaxanthin is the precursor for
      biosynthesis of apocarotenoids. Crocus zeaxanthin 7, 8 (7, 8)-cleavage
      dioxygenase gene (CsZCD) encodes a chromoplast enzyme that initiates the
      biogenesis of these apocarotenoids by cleaving zeaxanthin. The Reverse
      Transcription-PCR analysis revealed that CsZCD gene expression followed different
      patterns during stigma development. Highest levels of CsZCD gene expression was
      observed in fully developed scarlet stage of stigma. Real Time PCR analysis
      showed that there is a sharp increase in gene expression from yellow to orange
      and orange to scarlet stages of stigma development. Increase in CsZCD gene
      expression parallels with the apocarotenoid content during the development of
      stigma, suggesting its regulatory role for apocarotenoid biosynthesis and stigma
      development in saffron. 

PMID- 24082501
TI  - Female plants of Hippophae salicifolia D. Don are more responsive to cold stress
      than male plants.
AB  - Hippophae salicifolia D. Don (Seabuckthorn) grows in stressful environment of
      high altitude under conditions of low temperature and low availability of water.
      We have studied gender based differences in physiochemical response to cold
      stress in male and female plants of Seabuckthorn. After 24 h of cold stress about
      32 and 66 % higher electrolyte leakage (EL) was recorded in male and female
      plants respectively. Relative water content (RWC) at the end of 24 h stress was
      higher in male plants (~64 %) compared to female plants (~60 %). Proline content
      in leaf samples of cold stressed male and female plants also increased upon cold
      stress. After 24 h about 2.7 fold higher amount of proline was assessed in male
      and female in comparison to control plants. Similarly, about two fold increase in
      the specific activities of superoxide dismutase (SOD) and catalase was also
      observed upon cold stress in male and female plants. These findings have
      important inferences for community of molecular biologists exploring seabuckthorn
      genome for agronomically important genes. 

PMID- 24082502
TI  - Influencing micropropagation in Clitoria ternatea L. through the manipulation of
      TDZ levels and use of different explant types.
AB  - A comparative performance of two explants types (CN and Nodal) for their
      efficiency to induce multiple shoot regeneration in Clitoria ternatea has been
      carried out. Thidiazuron (TDZ) in different concentrations (0.05-2.5 MUM) was
      used as a supplement to the Murashige and Skoog's (MS) basal media. Explant type
      apart, two factors viz. concentration and exposure duration to TDZ played an
      important role in affecting multiple shoot regeneration. Cotyledonary node
      explants produced the best results at 0.1 MUM TDZ, while in nodal explants the
      highest rate of shoot formation was achieved on MS medium supplemented with 1.0
      MUM TDZ. In both the explants, shoot multiplication increased when the
      regenerated shoots were subcultured on hormone free MS medium after 4 weeks of
      exposure to TDZ. Among the two, cotyledonary node explants produced considerably
      higher number of shoots at a comparatively lower concentration of TDZ than nodal
      explants. The regenerated shoots rooted best on MS medium containing 1.0 MUM
      indole-3-butyric acid (IBA) and were successfully established in pots containing
      garden soil with 88 % survival rate. All the regenerated plants showed normal
      morphology and growth characteristics. 

PMID- 24082503
TI  - Induction of somatic embryogenesis in gum arabic tree [Acacia senegal (L.)
      Willd].
AB  - Factors affecting somatic embryogenesis from immature cotyledon of gum arabic
      tree [Acacia senegal (L.) Willd.] were investigated. Induction of somatic
      embryogenesis was influenced by plant growth regulator concentrations and
      addition of amino acids in medium. Best induction of somatic embryogenesis was
      obtained on MS medium supplemented with 0.45 MUM 2, 4-D, 2.32 MUM Kin and 15 mM L
      glutamine. L-glutamine plays a significant role in the maturation of somatic
      embryos and most of embryos attained maturity only on L-glutamine (15 mM)
      containing medium. Maximum percent (75.0 +/- 2.5) germination of somatic embryos
      was recorded on medium containing 0.22 MUM BAP. 

PMID- 24082504
TI  - Chemopreventive Effect of Bauhinia Purpurea Against Chemically Induced
      Hepatocarcinogenesis via Amelioration of Oxidative Damage, Cell Proliferation and
      Induction of Apoptosis in Wistar Rats.
AB  - OBJECTIVES: In the present study we have evaluated the chemopreventive efficacy
      of Bauhinia purpurea against Diethylnitrosamine (DEN) initiated and 2
      Acetylaminofluorine (2-AAF) promoted hepatocarcinogenesis in Wistar rats.
      MATERIALS AND METHODS: Efficacy of Bauhinia purpurea against 2-AAF-induced
      hepatotoxicity was evaluated in terms of biochemical estimation of antioxidant
      enzyme activities (reduced hepatic GSH, glutathione peroxidase, glutathione
      reductase, catalase, and quinone reductase), histopathological changes and
      expressions of early tumor markers viz., ornithine decarboxylase activity (ODC)
      and proliferating cell nuclear antigen (PCNA) and also expressions of p53, Bax,
      Bcl-2, and caspase-3 were evaluated. RESULTS: Oral pretreatment with B. purpurea
      significantly decreased the levels of serum toxicity markers, elevated
      antioxidant defense enzyme activities, suppressed the expression of ODC and PCNA
      and P53 along with the induction of apoptosis in the pretreatment groups. Tumor
      incidences are reduced by pretreatment of B. purpurea. Histopathological findings
      revealed that B. purpurea-pretreated groups showed marked recovery. CONCLUSION:
      The results support the protective effect of B. purpurea against chemically
      induced liver cancer and acts possibily by virtue of its antioxidant,
      antiproliferative, and apoptotic activities.

PMID- 24082505
TI  - Chlordiazepoxide preventive effect on tramadol overdose induced serotonin
      syndrome evaluated by hunter and radomski criteria: a clinical trial.
AB  - INTRODUCTION: Tramadol is an analgesic medication that is frequently abused. It
      has two functions; mu-opioid receptors agonism, as well as, serotonergic
      activities. It has shown that tramadol overdose may induce serotonin syndrome
      (SS). This study evaluates whether early treatment with chlordiazepoxide could
      prevent SS in admitted tramadol overdoses. MATERIALS AND METHODS: In this single
      blind randomized control trial, 50% of admitted tramadol overdoses in Imam Reza
      (p) Hospital from 21 September 2011 to 21 January 2012 were recruited. Cases
      received chlordiazepoxide and controls received placebo. Clinical findings were
      recorded in a pre-designed spread sheet every 6 hours in the first 24 hours of
      admission. SS was determined by two independent methods; Hunter Criteria (HC) and
      Radomski Criteria (RC). RESULTS: In total, five patients developed SS when HC or
      RC was taken into account. Among them, four cases were shared. None of the SS
      cases diagnosed with HC received chlordiazepoxide. However, just one SS case
      diagnosed with RC was from the case group. Based on HC, chlordiazepoxide
      decreased the Risk Ratio (CI 95%) of SS to 0.80 (0.66-0.97) (P = 0.025). This
      effect did not reach statistically significant levels when SS was diagnosed with
      RC. CONCLUSION: This study supports the fact that pre-treatment with
      chlordiazepoxide could prevent tramadol overdose induced SS.

PMID- 24082506
TI  - Potentiation of the hepatic toxicity of carbon disulfide by chlordane.
AB  - OBJECTIVES: In this study, we investigated whether cytochrome P450s (CYPs)
      induced by a typical chlorinated hydrocarbon insecticide chlordane (CLD)
      potentiate hepatic toxicity of carbon disulfide (CS2). MATERIALS AND METHODS:
      Male Sprague-Dawley rats were treated with CLD (25 mg/kg, intraperitoneally
      (i.p.)) daily for 4 days, and 24 h after the final injection the rats were
      treated with CS2 (380 mg/kg, i.p.) in corn oil; while controls received the
      vehicle alone. The rats were then sacrificed at 3, 6, and 24 h following the CS2
      treatment. RESULTS: It was found that at 3 h post-treatment, total hepatic
      glutathione (GSH) decreased modestly, but lipid peroxidation increased markedly,
      while all CLD-inducible CYPs (1A1, 2B1, 2E1, and 3A2) were inhibited by CS2
      variably but significantly. On the other hand, samples taken at 24 h following
      the CS2 treatment showed a significant increase in relative liver weights,
      hepatic GSH and lipid peroxidation, microsomal reactive oxygen species (ROS), and
      serum alanine transaminase (ALT) level. Activity of the CYPs was also increased,
      but remained significantly depressed, especially that of CYP2B1. Livers removed
      at 3 and 6 h after CS2 treatment showed subtle to distinct apoptotic changes,
      while a severe lesion of hydropic degeneration of the centrilobular cells with
      apoptosis was microscopically distinguishable in samples taken at 24 h.
      CONCLUSIONS: These results suggest that the metabolism of CS2 by CLD-induced CYPs
      and the generation of lipid peroxides may have in concert contributed to the
      distinct hepatocellular damage.

PMID- 24082507
TI  - Effects of Fennel Essential Oil on Cisplatin-induced Nephrotoxicity in
      Ovariectomized Rats.
AB  - BACKGROUND: Cisplatin (cis-diamminedichloroplatinum II (CDDP)) is an effective
      drug in cancer therapy to treat solid tumors. However, the drug is accompanied by
      nephrotoxicity. Previous reports indicated that estrogen has no protective role
      against CDDP-induced nephrotoxicity, but the role of phytoestrogen as an
      estrogenic agent in plants is not determined yet. The major composition of fennel
      essential oil (FEO) is trans-anethole that has estrogenic activity; so, we used
      FEO as a phytoestrogen source against CDDP-induced nephrotoxicity. MATERIALS AND
      METHODS: Fifty-four ovariectomized Wistar rats were divided into seven groups.
      Groups 1-3 received different doses of FEO (250, 500, and 1000 mg/kg/day,
      respectively) for 10 days. Group 4 received saline for 10 days plus single dose
      of CDDP (7 mg/kg, intraperitoneally (ip)) at day 3. Groups 5-7 received FEO
      similar to groups 1-3, respectively; plus a single dose of CDDP (7 mg/kg, ip) on
      day 3. On day 10, the animals were sacrificed for histopathological studies.
      RESULTS: The serum levels of blood urea nitrogen (BUN) and creatinine (Cr),
      kidney tissue damage score (KTDS), and kidney weight (KW) and body weight changes
      in CDDP-treated groups increased significantly (P < 0.05). FEO did not reduce the
      levels of BUN and Cr, KTDS, and KW and body weight changes. Also, the serum and
      tissue levels of nitrite were not altered significantly by FEO. CONCLUSION: FEO,
      as a source of phytoestrogen, did not induce kidney damage. In addition, FEO
      similar to estrogen was not a nephroprotectant agent against CDDP-induced
      nephrotoxicity.

PMID- 24082508
TI  - Possible role of plasma ceruloplasmin and erythrocyte sedimentation rate in
      assessing compliance with occupational hygiene and safety practices in waste
      management workers.
AB  - OBJECTIVES: Work-related health and safety risks are common among waste
      management workers (WMWs). This study investigated the level of compliance with
      safety measures in relation to levels of inflammatory markers among WMWs in
      Sagamu, South-West Nigeria. MATERIALS AND METHODS: WMWs comprising 30 cart
      pushers (CPs) and 50 truck users (TUs) were recruited alongside 45 people from
      the normal population as control. Data on health complaints were obtained from
      questionnaire surveys. Inflammation was assessed by measuring plasma
      ceruloplasmin (Cp), erythrocyte sedimentation rate (ESR), C-reactive protein
      (CRP), and albumin. RESULTS: WMWs exhibited a significantly higher prevalence of
      respiratory and gastrointestinal symptoms and poor compliance with health and
      safety measures. Significant (P < 0.001) differences were observed in the use of
      masks, hand gloves, protective clothing, and footwear between TUs and CPs. ESR,
      Cp, and CRP increased significantly (P < 0.001) by 145, 28.7, and 42.5% in TUs
      and by 164, 50.5, and 74.3% in CPs, respectively, relative to control. Negative
      correlation was observed between use of mask (r = -0.225, P < 0.01), use of
      gloves (r = -0.184, P < 0.05), and Cp and between ESR and washing of hands with
      soap (r = -0.185, P < 0.05). The use of goggles (r = +0.285, P < 0.001), washing
      of hands with soap (r = +0.203; P < 0.01), use of masks (r = +0.317, P < 0.001),
      and use of gloves correlated positively in WMWs. CONCLUSIONS: A higher prevalence
      of work-related symptoms and elevated inflammatory markers in WMWs was related to
      poor compliance with safety measures. ESR and Cp may be useful predictors of
      occupational hygiene and compliance with safety measures among Nigerian WMWs.

PMID- 24082509
TI  - Assessment of serum cholinesterase in rural punjabi sprayers exposed to a mixture
      of pesticides.
AB  - Serum cholinesterase (SChE) activity is considered as a biomarker and is also
      taken as an exposure index to assess the low level, chronic residue exposures
      among sprayers. Thus, cholinesterase activity was studied in the professional
      rural Punjabi sprayers of Bathinda district in Punjab. This study was made to
      estimate the irregularities in the level of cholinesterase according to multiple
      pesticides used by sprayers, exposure periods, age, and body mass index (BMI) of
      the sprayers. The data generated was statistically analyzed by applying Student's
      't' test and one-way analysis of variance. A positive correlation was found
      between SChE activity and years of exposure and a significant reduction in SChE
      activity was observed in younger population. Again, a positive correlation was
      seen between BMI and SChE inhibition. 

PMID- 24082510
TI  - Preliminary morphological and immunohistochemical changes in rat hippocampus
      following postnatal exposure to sodium arsenite.
AB  - The effects of arsenic exposure during rapid brain growth period (RBGP)
      (postnatal period 4-11) on pyramidal neurons of cornu ammonis (specifically CA1
      and CA3 regions) and granule cells of dentate gyrus (DG) of rat hippocampus were
      studied. Wistar rat pups, subdivided into the control (group I) and the
      experimental groups (group II, III, and IV), received distilled water and sodium
      arsenite (aqueous solution of 1.0, 1.5, and 2.0 mg/kg body weight, respectively)
      by intraperitoneal (i.p.) route. On postnatal day (PND) 12, the animals were
      sacrificed and brain tissue obtained. Paraffin sections (8 MUm thick) stained
      with Cresyl Violet (CV) were observed for morphological and morphometric
      parameters. Arsenic induced programmed cell death (apoptosis) was studied using
      Terminal deoxyribonucleotidyl transferase mediated dUTP biotin Nick End Labeling
      (TUNEL) technique on the paraffin sections. Microscopy revealed decreased number
      and isolation of pyramidal neurons in superficial layers, misalignments of
      pyramidal cells in stratum pyramidale (SP) of CA1 and CA3 in experimental group
      III and IV, and presence of polymorphic cells in subgranular zone of ectal limb
      of dentate gyrus (suggestive of arsenic induced proliferation and migration of
      granule cells in the dentate gyrus). Morphometric assessments quantified and
      confirmed the microscopic findings. The mean nuclear area of pyramidal cells was
      increased and cell density was decreased in the CA1, CA3, and DG of experimental
      groups in comparison to the control group. Increase in the TUNEL positive cells
      in DG was observed in the experimental group IV, suggestive of increased
      apoptosis. These observations confirm vulnerability of pyramidal (CA1, CA3) and
      granule cells (DG) of hippocampus during RBGP. 

PMID- 24082511
TI  - Evaluation of adverse effects of lisinopril and rosuvastatin on hematological and
      biochemical analytes in wistar rats.
AB  - OBJECTIVE: Combination therapy of lisinopril and rosuvastatin may be an important
      concept in developing more effective strategies to treat and prevent
      atherosclerosis, coronary heart disease, and co-morbid metabolic disorders. The
      present study was designed to evaluate toxic effects of lisinopril and
      rosuvastatin alone or its combination therapy on hematological and biochemical
      analytes in Wistar rats. MATERIALS AND METHODS: Forty-two rats were divided into
      seven groups, with each group comprising six rats. Rats were administered with
      lisinopril, rosuvastatin alone, or in-combination at two different doses. The
      blood samples were collected from rats after 21 days of oral administration of
      the drug/s and analyzed for various hematological and biochemical analytes.
      RESULTS: Lisinopril alone and its combination treatment with rosuvastatin at high
      doses decreased hemoglobin and hematocrit. Rosuvastatin alone at high dose and
      its concomitant administration with lisinopril at two different doses showed
      increase in total white blood cells and absolute lymphocyte count and neutrophil
      count. Serum levels of aspartate aminotransferase (AST), alkaline phosphatase
      (ALP), and total bilirubin were significantly increased in rosuvastatin alone and
      its combination with lisinopril at both the doses. Besides this, lisinopril
      treatment decreased serum levels of sodium and increased the levels of potassium.
      Serum creatine kinase (CK) levels were increased in the animals treated with
      rosuvastatin at both the doses. However, increased serum CK level because of
      rosuvastatin became normal with co-administration of lisinopril at low doses.
      CONCLUSION: Our results indicate that administration of lisinopril with
      rosuvastatin does not ameliorate hepatotoxicity caused by rosuvastatin. However,
      combination treatment reduces serum CK levels elevated due to rosuvastatin,
      implicating protective effect of combination treatment on myopathy at low doses.

PMID- 24082512
TI  - Differences in the expression and sensitivity of cultured rat brain neuronal and
      glial cells toward the monocrotophos.
AB  - Inducible expressions cytochrome P450s (CYPs) against environmental chemicals in
      brain tissues of experimental animals is well-documented. However, the precise
      role of specific brain cell type in the metabolism of different class of
      xenobiotics has not been explored adequately. We study the expression of selected
      CYPs (1A1/1A2, 2B1/2B2, 2E1) in primary cultures of rat brain neuronal and glial
      cell exposed to an organophosphate pesticide-monocrotophos (MCP), a known
      neurotoxicant. The cultured neurons and glial cells express significant
      expression of CYP1A1, 2B2 and 2E1 isoenzymes, where the levels were comparatively
      higher in neuronal cells. Neuronal cells exhibited greater induction of CYP2E1
      against MCP exposure, while glial cells were having more vulnerability for CYP1A
      and 2B isoenzymes. Similarly, cells were showing substrate specific responses
      against the specific inducers of CYPs, that is, ethanol (2E1), cyclophosphamide
      (2B1/2B2), 3-methylcholanthrene (1A1/1A2). The altered expression and activity of
      selected CYPs in cultured neuronal and glial cells could be helpful in explaining
      the association between MCP-induced neurotoxicity/metabolism and synthesis or
      transport of the neurotransmitters. The induction of CYPs in glial cells may also
      have significance as these cells are thought to be involved in protecting the
      neurons from environmental insults and safeguard them from toxicity. The
      differential expression pattern of CYPs in neuronal and glial cells exposed to
      MCP also indicate the selective sensitivity of these cells against the
      xenobiotics, hence suggested their suitability as tool to screen neurotoxicity
      potential of variety of xenobiotics. 

PMID- 24082513
TI  - An unusual case of refractory metabolic acidosis.
AB  - Homeopathy is one of the most frequently used systems of complementary and
      alternative medicine. The patients who seek homeopathic treatment are primarily
      those suffering from long-standing, chronic diseases. These medicines may have
      considerable risk of severe side effects. Some homeopathic medicinal preparations
      use alcohol as a base and are frequently prescribed for common conditions. We
      hereby report an unusual case of refractory metabolic acidosis after homeopathic
      medicinal treatment. 

PMID- 24082514
TI  - A rare neurological complication of acute organophosphorous poisoning.
AB  - Organophosphorous (OP) compound poisoning is one of the most common causes for
      admission to the Medical Intensive Care Unit. The morbidity and mortality
      associated with OP poisoning is due to the action of the compound at the
      muscarinic, nicotinic receptors, and the central nervous system. Here is a rare
      case of extrapyramidal manifestations occurring in the intermediate phase of OP
      poisoning, use of amantidine led to subsiding of the symptoms. 

PMID- 24082515
TI  - Intra-aural Route of Insecticide Poisoning.
AB  - Organophosphate (OP) compounds are commonly ingested with the intention of
      deliberate self-harm. Parenteral route of OP compound exposure is an uncommon yet
      significant source of toxicity. Deliberate injections via intravenous,
      intramuscular, and subcutaneous routes and accidental dermal absorption due to
      occupational exposure have been described earlier. We report an unusual case of
      intentional insecticide poisoning by pouring the OP compound into both ears. This
      was successfully treated with aural irrigation using normal saline and prompt
      administration of the antidote. 

PMID- 24082516
TI  - Systemic toxicity of local anesthetics: a point to ponder.

PMID- 24082517
TI  - Intestinal parasitic infection in Bhil tribe of Rajasthan, India.
AB  - A total of 224 Bhil tribal individuals (115 males and 109 females) of different
      age groups inhabiting tribal rural areas of Udaipur district of Rajasthan, India
      were investigated for the prevalence of intestinal parasitic (protozoan and
      helminths) infections. Fresh stool samples of these tribal subjects were examined
      microscopically by direct wet smear with saline and 1 % Lugol's iodine and
      formaline ether concentration. Of these 116 (51.78 %) were found to be infected
      with diverse species of intestinal parasites. Male individuals showed relatively
      higher (56.52 %) prevalence of infection as compared to their counterparts (46.78
      %). Out of 116 infected tribal subjects, 53 (23.66 %), 33 (14.73 %) and 30 (13.39
      %) were infected with protozoan, helminths and mixed (protozoan + helminths)
      parasitic infections, respectively. Maximum number of parasitic infections
      occurred in the age group of 6-10 years (69.23 %) in both sexes. Among the
      intestinal parasites, Entamoeba histolytica was the commonest (14.73 %) followed
      by Entamoeba coli (8.92 %), Taenia solium (5.35 %), Ascaris lumbricoides (4.46
      %), Hymenolepis nana (2.23 %), Ancylostoma duodenale (0.89 %), Strongyloides
      stercoralis (0.89 %), Trichuris trichiura (0.44 %) and Hymenolepis diminuta (0.44
      %). Data pertaining to distribution of parasite species in different age groups,
      and variation in prevalence of their infection in relation to age and sex were
      also analysed statistically and found to be significant. Possible causes for
      variation in prevalence of protozoan and helminthic infection are discussed. 

PMID- 24082518
TI  - Efficacy of indigenous entomopathogenic nematodes from Meghalaya, India against
      the larvae of taro leaf beetle, Aplosonyx chalybaeus (Hope).
AB  - The efficacy of three entomopathogenic nematode (EPN) species, Heterorhabditis
      indica, Steinernema thermophilum, and S. glaseri, from Meghalaya, India was
      studied against the larvae of taro leaf beetle, Aplosonyx chalybaeus (Hope)
      (Coleoptera: Chrysomelidae), under the laboratory conditions. The beetle larvae
      (grubs) were exposed to 25, 50, 75, 100 and 200 infective juveniles (IJs) of each
      nematode species for different time periods and they were found to be susceptible
      to all the EPNs tested. However, the susceptibility of grubs to nematode
      infection varied according to the dosages of IJs and their exposure periods.
      Appreciably good performance was achieved by S. glaseri, which showed 100 %
      mortality of insect larvae in 48 h exposure time. At 48 h of incubation, its LC50
      value was 90.3 IJs/larva, which was lower than that of S. thermophilum (115.0
      IJs/larva) and H. indica (186.0 IJs/larva), at the same exposure time. All the
      tested nematode species were also found to reproduce within the host and produced
      infective juveniles. H. indica, however, showed comparatively more production of
      IJs per cadaver of infected host (168.9 * 10(3) IJs/larva), as compared to the
      other two tested nematode species. The production of IJs per cadaver of infected
      host by S. thermophilum was recorded to be 82.0 * 10(3) IJs/larva. In case of S.
      glaseri, while production of IJs increased initially to 18.9 * 10(3) IJs/larva at
      concentration of 100 IJs/larva, it declined thereafter to 14.7 * 10(3) IJs/larva
      at the dose of 200 IJs/larva. In conclusion, the evidence obtained in this study
      suggests that all the three indigenous EPN species are virulent enough to produce
      100 % mortality in the last instar larvae of A. chalybaeus. These EPN species
      thus have potential scope for the management of A. chalybaeus in taro crops. 

PMID- 24082519
TI  - Effect of attractant sex pheromone on immature larval stages of ixodid tick
      species.
AB  - Attractant sex pheromone (ASP) 2,6-dichloro phenol was used in the current study
      to evaluate the percentage attraction and the behavioural responses of the five
      ixodid tick species namely Rhipicephalus sanguineus, Rhipicephalus microplus
      (Boophilus microplus), Haemaphysalis bispinosa, Rhipicephalus haemaphysaloides
      and Hyalomma marginatum using petridish bioassay. Two concentrations of 2,6-DCP
      (0.1 M and 0.05 M) was used for the larval stages of all five ixodid tick species
      of which 0.1 M concentration was found to have maximum attraction. Trials with
      0.1 M ASP revealed highest per cent of attraction in R. sanguineus larvae (71 %)
      followed by H. bispinosa (55 %) and R. microplus (55 %). With 0.1 M ASP R.
      haemaphysaloides and H. marginatum showed least attraction (39 % each). However
      the per cent of attraction of R. haemaphysaloides was higher (46 %) with 0.05 M
      ASP. Statistical analysis revealed a highly significant difference in per cent of
      attraction between the different tick larvae using 0.05 and 0.1 M ASP. The larvae
      also exhibited behavioural responses such as feeding, probing, resting and
      questing posture. 

PMID- 24082520
TI  - Seroprevalence of Toxoplasma gondii in southern districts of Tamil Nadu using IgG
      ELISA.
AB  - The present study was conducted to assess the seroprevalence of Toxoplasma gondii
      in and around Tirunelveli by in-house IgG assay using ELISA. Serum samples from
      175 immunodeficient and 175 immunocompetent patients were collected at
      Tirunelveli district, Tamil Nadu from May 2006 to October 2007. They were
      subjected into in-house IgG assay using enzyme-linked immune sorbent assay
      (ELISA) in which tachyzoite soluble antigen derived from solubilised whole
      organisms was used. Out of 350 patients tested by IgG ELISA, 46 patients (13.14%)
      had antibodies for toxoplasmosis with mean OD value of 0.2 +/- 0.073 and the OD
      value ranged from 0.144 to 0.444. Among the immunocompetent group of 175
      patients, 19 patients (10.86%) had antibodies to toxoplasmosis whereas, in
      immunodeficient group of 175 patients, 27 patients (15.43%) had antibodies for
      toxoplasmosis. There was no statistical difference (P > 0.05) between the
      immunocompetent and immunodeficient group. The sensitivity and specificity of IgG
      ELISA in detecting toxoplasmosis was 90 and 100%, respectively. The overall
      seroprevalence of toxoplasmosis in and around Tirunelveli district of Tamil Nadu
      was 13.14% based on IgG ELISA. The study has proved ELISA to be a sensitive and
      specific procedure for the serodiagnosis of toxoplasmosis. 

PMID- 24082521
TI  - Community ecology of the metazoan parasites of the Indian mackerel Rastrelliger
      kanagurta (Scombridae) from the coast of Visakhapatnam, Bay of Bengal.
AB  - One hundred and eighty four specimens of the mackerel Rastrelliger kanagurta
      collected from fish landings at Visakhapatnam coast, Bay of Bengal, between
      January 2006 and 2007, were examined for analysis of their metazoan parasite
      community structure at infra and component community levels and study the effects
      of season and host body length on these communities. Fifteen species of metazoan
      parasites were collected including 3 spp. Monogenea, 7 spp. Digenea and 5 spp.
      Copepoda. All the fish were parasitized by one or more metazoan parasite species.
      A total of 2,004 parasites were collected with a mean of 10.9. The majority were
      digeneans accounting for 42.4% of total number of parasites collected and the
      hemiurid Lecithocladium angustiovum is found to be the most dominant species.
      Mean values of species richness (3.0 +/- 1.5), abundance (12.4 +/- 9.3) and
      diversity (H' = 0.92) were within ranges observed for most of the metazoan
      parasite communities of marine fish from temperate and tropical countries.
      Seasonally, the mean diversity and parasite species richness of infracommunities
      were high during December and January and low during September-October. No
      correlation was found between host total length and any of the community
      descriptors. Most of the parasites i.e., 12 out of 15 species of parasites
      collected were host specialists. Only one species Aponurus laguncula was a host
      generalist. All taxa of metazoan parasites showed a typical over-dispersed
      pattern of distribution. The dominance of the core species in all the
      infracommunities and the high degree of host specialization of the parasite
      species resulted in the predictable component in the infracommunities to be high,
      each infra community comprising a core species accompanied by a few secondary
      species. 

PMID- 24082522
TI  - Successful treatment of pulmonary paragonimiasis in a German shepherd dog with
      fenbendazole.
AB  - Pulmonary paragonimiasis is an important zoonotic disease reported from many
      parts of the world. It is an endemic problem in human population in north-eastern
      states of India. There seems no report of pulmonary paragonimiasis in canine
      population from India. The present case describes first report of pulmonary
      paragonimiasis in a female dog suggesting possibility of this fluke becoming
      established in canine population in the country. The dog revealed mild coughing
      with serous nasal discharge. Faecal sample revealed eggs of Paragonimus spp.
      Treatment with fenbendazole resulted in marked improvement as revealed by
      clinical signs and chest radiography. 

PMID- 24082523
TI  - Evaluation of the efficacy of three indigenous strains of entomopathogenic
      nematodes from Meghalaya, India against mustard sawfly, Athalia lugens proxima
      Klug (Hymenoptera: Tenthredinidae).
AB  - The objective of this study was to evaluate the efficacy of three indigenous
      strains of entomopathogenic nematodes (EPN) from Meghalaya, India, namely
      Heterorhabditis indica Poinar, Karunakar and David, Steinernema thermophilum
      Ganguly and Singh, and Steinernema glaseri (Steiner) against the last instar
      larva of mustard sawfly, Athalia lugens proxima Klug, a serious pest of mustard
      and radish in India. The larvae of A. lugens proxima were exposed to 10, 25, 50,
      75 and 100 infective juveniles (IJs) concentration of each nematode species in
      Petri dishes. Percentage larval mortality and nematode reproduction in insect
      larvae was studied. The sawfly larvae were found to be susceptible to all the
      three EPNs tested, but the degree of susceptibility to infection varied from
      among nematode species. Based on LC50 value, H. indica was the most pathogenic
      species. Nevertheless, S. thermophilum and S. glaseri also showed a high insect
      mortality. This study also revealed that all the three test nematodes are also
      able to propagate in the host cadaver and produce first generation infective
      juveniles. However, H. indica produced significantly more number of IJs per
      insect larva than the other two nematode species. The progeny production was
      recorded to be the least in case of S. glaseri. In conclusion, our findings
      suggest that of the three indigenous EPNs studied, H. indica and S. thermophilum
      have good potential as biological control agents against mustard sawfly, A.
      lugens proxima. 

PMID- 24082524
TI  - An occurrence of clinical eperythrozoonosis in a German Shepherd dog and its
      therapeutic management.
AB  - Eperythrozoon spp.-a rickettsial (Mycoplasma) pathogen of the mammalian
      erythrocytic cell membrane, has been recognised to cause non specific, sporadic,
      febrile and haemolytic clinical disease in a variety of livestock, especially
      food animals. However, clinical eperythrozoonosis in companion animals seems not
      documented so far. An adult male German shepherd dog, aged 10.5 years and
      weighing 45 kg with clinical history of persistent mild fever in morning hours,
      depression and anorexia for the past 5 days and nasal bleeding for the past few
      months, was presented to clinicians for therapeutic management. Microscopic
      examination of Giemsa stained blood smear evidenced characteristic light pinkish
      to blue stained cocci and/or short rod shaped pathogens identified as
      Eperythrozoon canis, nesting in the depressions on the periphery of erythrocyte
      cell membrane as well as extra cellular free bodies in the plasma. Rhinoscopic
      detailed investigation failed to demonstrate any lesion in the nasal passage that
      could be attributed to the frequent nasal bleeding for the past few months. The
      dog was subsequently therapeutically managed with success using specific therapy
      and followed by supportive therapy. Finally, the predisposing factors of the
      disease, reasons for frequent nasal bleeding, clinical course of the disease in
      canines and its public health significance vis-a-vis future projections have been
      discussed. 

PMID- 24082525
TI  - Community ecology of the metazoan parasites of freshwater fishes of Kerala.
AB  - The prevalence and mean intensity of metazoan parasite infection, the community
      characteristics (richness index, dominance index, evenness index and Shannon
      index of diversity) and the qualitative similarity of the metazoan parasite fauna
      among the species and families of the fishes were determined of 13 fish species
      of freshwater fishes of Kerala belonging to seven families. The metazoan parasite
      fauna of this geographical area is very diverse; it consisted of 33 species of
      parasites belonging to seven major taxa: ten species of Monogenea, nine Digenea,
      two Cestoda, six Nematoda, three Acanthocephala, two Copepoda and one Isopoda.
      Prevalence of infection ranged from 32.9% (Puntius vittatus) to 87.1% (Mystus
      oculatus) and mean intensity from 3.8 (Puntius vittatus) to 27.6 (Aplocheilus
      lineatus). The infra- and component communities of parasites were somewhat
      characteristic. The dominance pattern of the major taxa was in the order Digenea
      > Nematoda > Monogenea = Acanthocephala > Cestoda = Copepoda > Isopoda.
      Macropodus cupanus harboured the richest fauna and Puntius vittatus had the least
      rich fauna. The parasite fauna of A. lineatus was the most heterogeneous and that
      of M. cavasius, the most homogeneous. The diversity of the parasite fauna was the
      greatest in M. cavasius and the least in A. lineatus. The parasite faunas of A.
      lineatus and M. cupanus and of M. cavasius and M. oculatus were similar. However,
      in spite of the taxonomic nearness and the similarity of the habits and habitats
      of the four species of cyprinids (P. amphibius, P. filamentosus, P. sarana and P.
      vittatus), their parasite fauna were qualitatively very dissimilar-of the seven
      species of parasites encountered in them only one was shared by the four host
      species. The cyprinid, Rasbora daniconius, had its own characteristic component
      community of parasites consisting of six species none of which was shared by the
      other four cyprinids. The richest parasite fauna was that of the family
      Cyprinidae followed by that of Channidae and the poorest of Belonidae. The most
      homogeneous parasite fauna was that of Bagridae and the most heterogeneous that
      of Cyprinodontidae. The parasite fauna of Cyprinodontidae and Belontidae were
      qualitatively very similar. The results indicate that the freshwater fishes of
      the southwest cost of India harbour a rich and diverse metazoan parasite fauna,
      which is as rich and diverse as that of the marine fishes of this area. The
      results also suggest that carnivorous/omnivorous fish species harbour richer and
      more heterogeneous component communities of parasites than herbivorous species
      implying that the feeding habits of fishes is a major factor deciding their
      parasite faunas. 

PMID- 24082526
TI  - Histo-architectural alterations induced by Euclinostomum heterostomum
      (metacercariae) infected liver of Channa punctata (Bloch).
AB  - Present investigation was carried out to study the effect of digenetic trematode,
      Euclinostomum heretostomum on the histo-architecture of liver of Channa punctata.
      In case of mild infection, the metacercariae were found attached to the external
      surface of hepatic tissue. While in case of acute or chronic infection, the
      encysted metacercariae of Euclinostomum heterostomum were found deeply embedded
      in the entire hepatic tissue due to which liver appeared thin, compressed and
      pale with yellowish- black nodules of encysted metacercariae. A space occupying
      cavity is created by the metacercarial cysts due to which tissue appeared in the
      form of lumps. Histo-architectural alterations induced by parasite included
      degeneration, compression and loosening of hepatic tissue with enucleated and
      deshaped hepatocytes. 

PMID- 24082527
TI  - The prevalence of Linguatula serrata nymphs in goats slaughtered in Tabriz, Iran.
AB  - During 1 year (April 2009-April 2010), the prevalence of Linguatula serrata (L.
      serrata) nymphs in liver and mesenteric and mediastinal lymph nodes (MLN) of 740
      native goats of different sex and ages were examined in Tabriz, north west of
      Iran. Initially the organs were macroscopically examined for nymphal stage of L.
      serrata and then were digested by acid-pepsin method to further investigation.
      The prevalence rate was obtained 55.27%. The mesenteric lymph nodes (MLN) in 334
      (45.13%), the lymph nodes (LN) in 102 (13.78%) and the livers in 8 (1.08%) goats
      out of 740 were infected with L. serrata nymphs. The results indicated a high
      rate of infection of LN in goats in this region of Iran. 

PMID- 24082528
TI  - Apolocystis cognetti sp. nov. (Apicomplexa: Monocystinae) a new aseptate
      gregarine species from the earthworm Amynthas hawayanus (Annelida: Oligochaeta)
      from West Bengal, India.
AB  - During the course of surveys of endoparasitic aseptate gregarines in Darjeeling
      district of West Bengal, India, seminal vesicles of Amynthas hawayanus (Rosa
      1891) found to be infested with a new species of the genus Apolocystis (Cognetti
      de Martiis 1923). Trophozoites are spherical or rounded and without any polar
      differentiation. Diameter of the trophozoite ranges from 65.4 to 126.7 (91.8 +/-
      17.5) MUm. Nucleus diameter measures 12.2-20.4 (14.4 +/- 2.2) MUm. Gametocyst is
      round and measures 73.6-110.4 (93.3 +/- 14.0) MUm and contains two unequal
      gametocytes. Oocyst measures 7.7-10.7 (9.5 +/- 0.9) MUm * 3.8-5.3 (4.6 +/- 0.4)
      MUm. 

PMID- 24082529
TI  - Immunodiagnosis as an aid for early detection of Fasciola gigantica by
      glutathione S-transferase (GST).
AB  - In the present study, effort to isolate purified GST from Fasciola gigantica
      homogenate and its early detection for confirmation of infection has been
      successful. In this study, immunoprotection studies with GST and antibody titer
      post-infection has revealed GST to be an immunogenic protein with high
      sensitivity to detect anti-Fasciola antibody as early as two weeks post-infection
      in large ruminants. 

PMID- 24082530
TI  - Molecular characterization of surface antigen 3 (SAG3) gene of Toxoplasma gondii
      RH-IVRI strain.
AB  - Toxoplasmosis, caused by Toxoplasma gondii, is a zoonotic disease and is
      responsible for abortions, stillbirth, and neonatal complications in livestock,
      especially in sheep, goats, and pigs. The molecular characterization of the
      parasite having global distribution is considered important to delineate the
      phylogenetic relationship among different isolates/strains of the parasite. The
      present communication deals with the molecular cloning and sequence analysis of
      the 1,158 bp entire open reading frame of surface antigen 3 (SAG3) of T. gondii
      RH strain being maintained at the Indian Veterinary Research Institute (IVRI).
      The sequence comparison analysis revealed 99.9 % homology with the published
      sequence of T. gondii RH strain, with a single substitution of guanine 'G'
      instead of adenine 'A' at the 397th position of SAG3 sequence. The substitution
      of single nucleotide consequently resulted in the change of one amino acid
      residue of aspartic acid (D) instead of asparagine (N) present in the published
      sequence of RH strain. This denotes that the SAG3 gene of this RH strain has not
      undergone a major change in its molecular conformation even after repeated
      passage in mice for more than a decade at IVRI. The finding is important from the
      molecular phylogeny point of view. 

PMID- 24082531
TI  - Acute bilateral proptosis in a cross bred calf naturally infected with Theileria
      annulata.
AB  - Ever since 1970, Bovine tropical theleriosis has been recognized major constraint
      to livestock improvement programme in the semi- arid and enzootic areas of
      Rajasthan. In contrast to other apicomplexan protozoan infections of blood,
      pathophysiological impact of Theileria annulata has been incriminated to in situ
      intra-leucocytic development of the pathogen. In continuation with recent
      manifestations documented on trans-placental T. annulata in a 3 day old cross
      bred calf and cerebral form of bovine theleriosis "Turning Sickness" in an adult
      cow, herein an another interesting manifestation of the disease "exophthalmos"
      incriminated to congenitally acquired T. annulata infection in a cross bred calf,
      its pathogenesis and impact are being presented and discussed. 

PMID- 24082532
TI  - Prevalence of parasites and associated risk factors in domestic pigeons (Columba
      livia domestica) and free-range backyard chickens of Sistan region, east of Iran.
AB  - This study was carried out on free-range backyard chickens and domestic pigeons
      (Columba livia domestica) from December 2010 to November 2011 to determine the
      prevalence, intensity and species of internal and external parasites in Sistan
      region, east of Iran. Of the total of 59 (27 males and 32 females) free-range
      backyard chickens and 46 (26 males and 20 females) domestic pigeons inspected, 55
      (93.22 %) and 39 (84.78 %) were infected respectively. Ten species of free-range
      backyard chickens parasites were collected from alimentary canals, body, head and
      neck, comprising of 3 species of nematodes, 4 species of cestodes and 3 species
      of ectoparasites as follows: Ascaridia galli (16.94 %), Heterakis gallinarum
      (23.72 %), Subulura brumpti (67.79 %), Raillietina tetragona (35.59 %),
      Raillietina echinobothrida (27.11 %), Raillietina cesticillus (15.25 %),
      Choanotaenia infundibulum (40.67 %), Argas persicus (16.94 %), Menopen gallinae
      (55.93 %) and Menacanthus stramineus (33.89 %). The domestic pigeons were
      infected with seven species of parasites including 2 species of nematodes, 2
      species of cestodes and 3 species of ectoparasites as follows: Ascaridia colombae
      (15.21 %), Hadjelia truncata (17.39 %), Raillietina tetragona (26.08 %),
      Raillietina echinobothrida (28.26 %), Argas reflexus (13.04 %), Menopen gallinae
      (32.60 %), Columbicola Columba (41.30 %). This is the first survey to determine
      the prevalence and intensity of parasites among free-range backyard chicken and
      domestic pigeon species in Sistan region. 

PMID- 24082533
TI  - Turning sickness in a cross bred cow naturally infected with Theileria annulata.
AB  - Bovine tropical theileriosis (BTT) has been since long recognized as a persistent
      major constraint on genetic improvement programme of native cattle breeds under
      "Operation Flood". The disease accounts for high mortality in dairy cattle
      especially calves. A cross bred cow (Rathi * Holestein), aged 3 years and
      weighing ~300 kg, owned by a person from weaker sections of the society,
      initially suffered from ruminal hypotonocity, severe dyspnoea, frothy discharge,
      lacrymation, cessation of defaecation, anorexia besides, icterus, mild form of
      anaemia and moderately elevated temperature etc., for the past 48 h. The cow
      suddenly developed pre mortal fall in temperature and neurological signs
      suggestive of posterior paresis. Ante mortem laboratory investigations revealed
      Koch Blue Bodies in the lymphocytes and Theileria annulata meronts in the
      erythrocytes. The cerebral form of BTT in the instant case was differentiated and
      discussed with other diseases causing analogous neurological signs. 

PMID- 24082535
TI  - Identification of Dactylogyrus spp. and other parasites of common carp in
      northeast of Iran.
AB  - This research was carried out in order to get overview of current status of
      infestation with Dactylogyrus spp. and other parasites in common carp (Cyprinus
      carpio) collected from the ponds around Mashhad in northeast of Iran. A total of
      100 common carps from March to December 2011, 61 (61 %) specimens were hosts to
      parasites. Monogenea dominated the parasite load most of all fishes, whereas
      Argulus foliaceus (Arthropoda) was the less parasite. Parasites were found as
      followed: Dactylogyrus extensus (29 %), Dactylogyrus anchoratus (2 %),
      Ichthyophthirius multifiliis (10 %), Trichodina nigra (7 %), Capillaria spp. (5
      %), Procaecum spp. (2 %), Argulus foliaceus (2 %), and Lernaea cyprinacea (4 %).
      Seasonal changes in the abundance of parasites were evident for most taxa in
      which the prevalence of parasitic infection and diversity were more in summer
      than other seasons. The result of this study provide a better aquaculture
      conditions and help to solve some of the problems of fish farmers. 

PMID- 24082534
TI  - Prevalence of ixodid tick infestation of sheep in the Arasbaran region of Iran.
AB  - This survey was carried out in sheep herds of Arasbaran region in northwest of
      Iran. The aims of this survey were assessment of occurrence hard ticks on sheep
      in this region and speciation and identification of detached ticks from sheep. In
      addition determination of tick distribution on sheep body surface was studied. In
      this study 330 sheep were examined and ticks from infested animals were
      collected. In parasitological laboratory speciation of ticks were done by
      stereomicroscope and using of tick identification keys. Overall 525 ticks were
      collected from 132 infested sheep and speciation of these tick showed 4 genera
      and 6 species including: Hyalomma marginatum marginatum (65.33 %), Rhipicephalus
      bursa (26.66 %), Haemaphysalis choldokovsky (5.90 %), Dermacentor marginatus
      (1.71 %), Haemaphysalis punctata (0.19 %) and Hyalomma excavatum (0.19 %). The
      distribution of ticks on sheep body surface was as follow, according to its
      frequencies: tail (42.66 %), groin (25.71 %), axilla (24.19 %), neck (5.71 %) and
      sternum (1.71 %). It was concluded that H. m. marginatum was the dominant tick in
      sheep of Arasbaran region. 

PMID- 24082536
TI  - Scanning electron microscope study of a snake tick, Amblyomma gervaisi (Acari:
      Ixodidae).
AB  - The scanning electron microscope (SEM) studies on both male and female tick,
      Amblyomma gervaisi (Lucas 1847) inhabiting the snake Naja naja were made. Detail
      of the surface structures as seen under SEM exhibit sexual dimorphism and were
      compared with other tick species as reported. SEM observations show
      characteristic alloscutal ornamentation, inornate festoons, triangular licking
      organ, size of the hypostome, round Haller's organ, genital plate oval in male
      and slit-like in female, and prominent marginated anal plate. The findings of the
      present study address the diversity in surface ultrastructure among snake ticks
      which would help in tick biosystematics. 

PMID- 24082537
TI  - On a new species of the genus Cobboldina (Nematoda: Atractidae) from Hippopotamus
      (Hippopotamus amphibius Linnaeus, 1758) captivated at the Alipore Zoological
      Garden, Kolkata, West Bengal, India.
AB  - The specimens of the genus Cobboldina Leiper, 1911 and family Atractidae
      (Railliet, 1917) Travassos, 1919 recovered from the faecal matter of Hippopotamus
      (Hippopotamus amphibius Linnaeus, 1758) from the Alipore Zoological Garden,
      Kolkata, India recognized as a new species after careful observation. The
      collected nematode differs from the only valid species Cobboldina vivipara
      Leiper, 1911, in the presence of gubernaculum (13.2-29.7 MUm in length) and the
      number of caudal papillae (10 pairs) and named as Cobboldina gubernacularia sp.
      n., This is the second species of the genus Cobboldina recorded from the host
      Hippopotamus amphibius Linnaeus, 1758 remaining captive in the Alipore Zoological
      Garden, Kolkata, India. 

PMID- 24082538
TI  - Prevalence of parasitic infections in cattle of Ludhiana district, Punjab.
AB  - A total of 862 cattle were sampled for both haematological (703) and coprological
      (159) investigations at the Large Animal Clinics, GADVASU, Ludhiana, Punjab,
      India. Examination of Giemsa-stained peripheral blood smears exhibited that 22.9
      % (161/703) of cattle were infected with haematozoa comprising Theileria annulata
      (14.65 %), Trypanosoma evansi (0.28 %), Babesia bigemina (1.56 %) and Anaplasma
      marginale (8.53 %) while mixed infection appeared in 2.13 % (15/703) animals. The
      prevalence of total haemoparasites and A. marginale infections were significantly
      higher (p < 0.01) in younger animals <1 year of age whereas, T. evansi and A.
      marginale infections were significantly higher (p < 0.05) in males. Coprological
      examination revealed that the overall prevalence of gastrointestinal (GI)
      parasitic infection was 16.98 % (27/159). Among the revealed parasites,
      amphistomes, Fasciola spp., Eimeria spp., Balantidium coli, strongyles and
      Trichuris spp. were detected from 3.77, 1.88, 3.77, 2.52, 10.69 and 1.26 % of
      examined animals. Except coccidiosis, there was no significant variation of GI
      parasitic infections in relation to sex as Eimeria spp. were found higher (p <
      0.01) in males. The prevalence of Trichuris spp. was significantly higher (p <
      0.05) in younger animals <6 months of age. The present work emphasized that
      strongyles and T. annulata were the most prevalent GI and haemoparasites,
      respectively. 

PMID- 24082539
TI  - Pathological studies on experimental Trypanosoma evansi infection in Swiss albino
      mice.
AB  - The pathology of Trypanosoma evansi infection was studied in Swiss albino mice
      using cattle isolate of the parasite. Sixteen Swiss albino mice were used in the
      experiment and were divided into two groups viz. infected group (I) and
      uninfected healthy control group (II) comprising 12 and four mice, respectively.
      Twelve mice from group I were infected with 1 * 10(5) purified trypanosomes.
      Systematic necropsy examination specifically of the infected mice (group I) as
      well as of healthy control (group II) was performed and pathological changes were
      recorded. The different tissue samples were collected in 10 % neutral buffered
      formal saline and were used to study the histopathological changes. Gross post
      mortem examination revealed enlargement of spleen, petechial haemorrhages in
      liver in the terminal stages of disease. Tissue sections revealed presence of
      numerous trypanosomes in blood vessels of liver, spleen, brain and kidneys.
      Microscopically, liver revealed lesions varying from vacuolar degeneration,
      coagulative necrosis along with congestion and haemorrhages. Spleen showed
      extensive haemorrhages in red pulp area, haemosiderosis and aggregation of
      histiocytes resulting in multinuclear giant cell formation. Lungs revealed
      oedema, congestion and mild inflammatory changes. Brain revealed mild
      degenerative changes along with congestion of meningeal blood vessels. Kidneys
      showed tubular degeneration, congestion and cellular infiltration. Heart revealed
      mild degenerative changes along with interstitial oedema. All changes were
      consistent with trypanosome infection and were confirmed by presence of
      trypanosomes in most of the tissue sections examined. 

PMID- 24082541
TI  - Drug combination therapy in control of cryptosporidiosis in Ludhiana district of
      Punjab.
AB  - The present report describes outbreak of cryptosporidiosis in neonatal cross bred
      cattle calves ageing 1-2 months in an organized dairy farm. The protozoan
      infection was confirmed by identifying bright red oocysts of Cryptosporidium spp.
      in the faecal samples after staining with modified acid Fast Zeihl-Neelsen stain.
      Metronidazole and furazolidone combination was able to induce clinically and
      parasitological recovery. This is believed to be the first report on the
      successful use of this drug combination against cryptosporidiosis. 

PMID- 24082540
TI  - Hydatid disease in childhood: revisited report of an interesting case.
AB  - Hydatid disease is a zoonosis caused by the tapeworm of Echinococcus spp. The
      disease is widely endemic in many sheep and cattle rearing locales. However,
      hydatidosis does not remain restricted to endemic geographical locales anymore
      but rather is a global health concern. It is a major public health burden causing
      significant morbidity and mortality. Echinococcus granulosus involvement in
      children has a different pattern than adults. Children of all age groups are
      susceptible and localization of the disease in the lungs is more commonly seen.
      Multiple liver cysts in the paediatric age group is relatively uncommon. We
      report an interesting case of multiple liver cysts in a 5-year old boy which was
      diagnosed as hydatid cysts on histopathological examination. 

PMID- 24082542
TI  - Fatal esophageal fibrosarcoma associated to parasitism by spirurid nematode
      Spirocerca lupi in a dog: a case report.
AB  - A 7-years-old intact female mixed breed dog was referred to the private
      veterinary clinic because of history of intense food regurgitation. The plain X
      ray examination and the contrast-enhanced X-ray using barium sulfate revealed the
      presence of a radio-opaque mass in the final third of the esophagus. Stool
      samples were collected and the coproparasitological test was done, which showed
      thick-shelled eggs from Spirocerca lupi. As the canine died, the necropsy was
      performed, showing nodular lesions in the esophagus, compatible with the typical
      lesions of spirocercosis. The histopathological analysis showed the proliferation
      of spindle-shaped cells, process compatible with fibrosarcoma. This is the first
      official report of the presence of canine spirocercosis in Guapimirim city, Rio
      de Janeiro, Brazil, and can serve as a warning to veterinary practitioners, about
      this probably endemic region for S. lupi. 

PMID- 24082543
TI  - Myiasis in domestic animals: new records of calyptrate Diptera.
AB  - This paper reports one case of wound myiasis by Hemipyrellia ligurriens (Diptera,
      Calliphoridae) that occurred in a goat and three cases of vaginal myiasis, five
      cases of cutaneous myiasis and one case of hoof myiasis in goat, buffalo and bull
      respectively by Seniorwhitea reciproca (Diptera, Sarcophagidae), for the first
      time in West Bengal, India. 

PMID- 24082544
TI  - First record of Chrysomya albiceps Wiedemann, 1819 (Diptera: Calliphoridae)
      maggots from a sambar deer (Rusa unicolor) in Kerala, South India.
AB  - Fully grown third stage larvae (LIII) of Chrysomya albiceps were recovered from
      aberrant sites viz. trachea and rumen during necropsy of a free-range sambar deer
      that had been observed to bear an inflamed tongue infested with maggots and
      subsequently died due to starvation. Five dead maggots of C. bezziana were also
      recovered from rumen. The aberrant locations of the recovery of the maggots
      indicated that they might have reached these sites accidentally. This is the
      first report of LIII of C. albiceps from a sambar deer from Kerala, South India. 

PMID- 24082545
TI  - Histopathological effects of larval trematodes on the digestive gland of
      freshwater snail species, Vivipara bengalensis and Lymnaea acuminata.
AB  - Comparative histopathological effects were observed on the digestive glands
      (hepatopancreas) of freshwater snail species, Vivipara bengalensis and Lymnaea
      acuminata infected with single (furcocercous cercariae) and double infection of
      digenean trematode larvae (gymnocephalous cercariae + metacercariae),
      respectively. Digestive glands of both the snail species revealed degenerative
      changes in their digestive gland tubules. The latter became irregular in shape,
      reduced in size with enlarged lumen and inter-tubular space besides rupturing of
      digestive tubules. These changes were correlated with the size and types of
      trematode larvae, single or double infection and degree of parasitemia. Autolytic
      necrosis of numerous tubules was found in digestive glands infected with double
      and very severe single infection. None of the tubules was found to be invaded by
      sporocyst, redia and cercaria. However, metacercariae were seen to invade
      digestive tubules of Lymnaea species. 

PMID- 24082546
TI  - Management of large bowel injury during laparoscopic surgery.

PMID- 24082547
TI  - Indian contribution to obstetrics and gynecology.

PMID- 24082548
TI  - GnRH agonists: do they have a place in the modern management of fibroid disease?
AB  - In the management of women with fibroid disease, GnRH agonists (GnRHa) are
      frequently used to reduce volume and vascularity before myomectomy, apparently to
      render the operation easier and reduce operative blood loss, and to enable a
      transverse supra-pubic incision instead of a midline vertical one. They induce
      amenorrhoea and thus aid in the correction of pre-operative anaemia. Other
      gynaecologists use GnRHa to shrink sub mucous fibroids greater than 5 cm in
      diameter to facilitate access and reduce blood loss and operating time at
      transcervical resection. GnRHa are also occasionally used as a temporizing
      measure in women with symptomatic fibroids within the climacteric. We argue
      against the use of GnRHa in the management of fibroid disease because they are
      not cost effective, render myomectomy more difficult to apply because they
      destroy tissue planes, the more difficult enucleation in fact increasing rather
      than reducing peri-operative blood loss and operating time. When used before
      myomectomy, they increase the risk of 'recurrence' because they obscure smaller
      fibroids that 'recur' when the effects of the GnRHa wear off, and are associated
      with side effects in situations where they confer no benefits, or where
      alternative cheaper drugs with fewer side effects are available. 

PMID- 24082549
TI  - Prevalance of pregnancy associated asymptomatic bacteriuria: a study done in a
      tertiary care hospital.
AB  - OBJECTIVES: A prospective study was conducted in the Department of microbiology
      (IGMC) and the Department of obstetrics & gynecology (KNH), Shimla, and Himachal
      Pradesh over a period of 1 year from May 2005 to April 2006 on 463 asymptomatic
      pregnant females with a period of gestation (POG) 28 weeks or less. The aim was
      to find out the prevalence of pregnancy associated bacteriuria and bacterial
      causes responsible for this entity. METHODS: The pregnant women were taught to
      collect the urine sample by aseptic technique which was then subjected to semi
      quantitative culture method. RESULTS: Significant bacteriuria was present in
      7.34% cases. About 78% samples were found to be sterile. Insignificant count and
      growth of contaminants was positive in 1 and 13% samples, respectively. The most
      common etiological agent came out to be E. coli followed by other gram positive
      and gram negative organisms. CONCLUSION: Asymptomatic bacteriuria is a common
      occurrence which should be diagnosed and treated in early pregnancy keeping in
      view its adverse effects on pregnancy.

PMID- 24082550
TI  - Prenatal diagnosis in low resource setting: is it acceptable?
AB  - AIM: This study aimed to explore knowledge and acceptability of prenatal
      procedures both non-invasive prenatal screening tests and invasive procedures
      among Egyptian women in childbearing age and to assess their attitude toward such
      procedures. Also to examine confounding factors affecting women's attitude toward
      prenatal procedures. STUDY DESIGN: A cross-sectional study on a representative
      sample of women in childbearing age attending Obstetrics & Gynecology outpatient
      clinic at Mansoura University Hospital, Egypt. An anonymous questionnaire was
      supplemented by voluntary interviewers for women in childbearing age. RESULTS:
      465 women were included in the study. The mean age +/- SD was 27 +/- 6 years.
      About 44 % of women were knowledgeable about non-invasive prenatal screening
      procedure, and only 25.5 % had heard about invasive prenatal procedures. 88.8 %
      express positive attitude regarding performance of the screening tests. Forty-one
      percent of the group agreed to perform invasive prenatal procedures during their
      pregnancy. Educational level and family history of congenital anomalies
      significantly affected attitudes toward testing during future pregnancy. The cost
      of procedure affected the decision to perform in 56.7 % of women. CONCLUSION:
      Egyptian women express positive attitude toward non-invasive prenatal screening
      but showed poor knowledge. Their attitude toward invasive procedure is guarded by
      the risk of abortion. Education and family history of fetal anomalies are the
      factors that affect attitudes. The cost of the prenatal test affects the decision
      made by the women to participate in testing.

PMID- 24082551
TI  - Study of length of umbilical cord and fetal outcome: a study of 1,000 deliveries.
AB  - OBJECTIVE: To study the correlation of umbilical cord length with fetal
      parameters like Apgar score, sex, weight, and length, and its effect on labor
      outcome. DESIGN: Prospective study of 1,000 cases. SETTING: Government Hospital.
      MATERIAL AND METHOD: Examination of umbilical cord was done for any loop around
      neck, trunk, etc; no. of loops of cord and positions; Knots of cord (True or
      false), any cord abnormalities. Fetal parameters recorded were sex, weight, and
      length of the newborn. Fetal outcome studied by Apgar score at 1 and 5 min.
      RESULTS: In our study, the cord length varied from 24 to 124 cm. The mean cord
      length was 63.86 cm (+/-15.69 cm). Maximum cases seen were in the group of cord
      length between 51 and 60 cm. Lower 5th percentile was considered as short cord
      and upper 5th percentile was considered as long cord. Short-cord group was
      associated with significantly higher (p < 0.05) incidence of LSCS cases. Cord
      length did not vary according to the weight, length, and sex of the baby. The
      incidence of all types of cord complications increases as the cord length
      increases (p < 0.001*). Nuchal cords had higher mean cord length than in cases
      without nuchal cords (p < 0.001). As the number of loops in a nuchal cord
      increases to more than two loops, the operative interference increases. The
      significance was tested by using a Chi-square test, and it was found to be
      statistically significant (p < 0.05). Nuchal cords were seen to be associated
      with more cases of fetal heart abnormalities (p < 0.001). There is higher
      incidence of variability in fetal heart rate with extremes of cord length (p <
      0.001). The incidence of birth asphyxia was significantly more in long and short
      cords as compared to cords with normal cord length (p < 0.001). CONCLUSION: The
      present study showed that the length of umbilical cord is variable; however,
      maximum number of cases had normal cord length. Cases which had short and long
      cords constituted abnormal cord length. These cases had higher incidence of cord
      complications, increased incidence of operative interference, intrapartum
      complications, increased fetal heart rate abnormalities, and more chances of
      birth asphyxia. But cord length did not vary according to the weight, length, and
      sex of the baby.

PMID- 24082552
TI  - Role of neuroimaging in patients with atypical eclampsia.
AB  - NEED: Despite availability of intensive care units and improved antenatal care,
      some women still die from Eclampsia. Eclampsia is associated with increased risk
      of maternal death varying from 1.8 % in developed countries to 14 % in developing
      countries. Cerebral complications are the major cause of death in eclampsia
      patients. Eclampsia along with hypercoagulopathy of pregnancy is a high risk fact
      for patient in respect of development of cerebrovascular thrombosis/ischemic
      strokes. Eclampsia patients who are refractory to the routine treatment have been
      found to have various CNS pathological conditions amenable to the medical
      treatment. AIMS AND OBJECTIVES: (1) To study the neuropathophysiology behind an
      eclamptic seizure to reduce the morbidity associated with it. (2) To study the
      role of neuroimaging in patients with atypical eclampsia. METHODOLOGY:
      Prospective study design included 30 patients for the study. All patients were
      admitted in the eclampsia room with h/o convulsions. All patients were put on
      MgSO4 therapy and antihypertensives. The patients who are refractory to the
      treatment such as having recurrent convulsions despite therapy MgSO4 were
      selected for neuroimaging with CT scan. Neuroimaging is done using Phillips
      Tomoscan CT scanner where slices of 10-mm thickness were taken through the entire
      brain in the transaxial plane. Abdomen shielding is done with lead shield to
      prevent radiation hazard. RESULT: [Table: see text]. CONCLUSION: Eclampsia
      patients who were refractory to the treatment with MgSO4 and antihypertensives
      have been found to have very significant and morbid CNS pathological conditions.
      Neuroimaging in these patients have done a pivotal role in identifying the
      abnormality and rectifying it with medical means which had definitely improved
      patient's condition and have reduced morbidity.

PMID- 24082553
TI  - Outcome of breech deliveries in cameroonian nulliparous women.
AB  - OBJECTIVE: To evaluate nulliparous breech delivery so as to determine prognostic
      factors for an unsafe vaginal delivery (VD). METHODS: This retrospective and
      descriptive study was carried out in the University Teaching Hospital Yaounde
      Cameroon, from January 1, 2005 to December 31, 2009. Files of 126 women with
      singletons in breech presentation and normal fetal heart beats at a gestational
      age >=32 weeks were reviewed with a trial of VD ordered in 104. The parameters
      recorded were mother's age, gestational age, mode of delivery, birth weight, 5th
      minute Apgar scores, neonatal outcome, and use of episiotomy. RESULTS: The
      results showed that 84 (66.7 %) had a successful VD. Failure of VD or poor Apgar
      score after VD were observed if fetal weight >=3,500 or <1,800 g, footling
      breech, maternal age >28 or <19 years, post term, and rigid cervix. CONCLUSIONS:
      Elective cesarean section should be systematic if the unsafe circumstances above
      mentioned are present.

PMID- 24082554
TI  - Study of thrombophilia in recurrent pregnancy loss.
AB  - OBJECTIVES: Recently, it has been found that women who have thrombophilia have
      increased risk of fetal loss. This study was designed to corroborate the
      association of elevated factor VIII level, protein C and protein S deficiencies,
      and the presence of LAC in women with recurrent pregnancy loss. MATERIALS AND
      METHODS: 53 patients with history of two or more pregnancy losses and 47 healthy
      age-matched subjects with no history of pregnancy loss and who have delivered at
      least one term infant without any complication were enrolled into the study.
      RESULTS: Thrombophilic defect was present in 64.15 % of patients of study group.
      Protein S deficiency (50.94 %) was the most common thrombophilic defect observed.
      Spontaneous abortion (SA), preterm birth (PTB), and intrauterine growth
      retardation (IUGR) were the most important pregnancy complications observed. The
      strongest associations of pregnancy complications were observed with protein S
      deficiency (87.5 %) and with elevated factor VIII (66.66 %) level. CONCLUSION:
      This study observed strong association of thrombophilia with unexplained
      recurrent pregnancy loss.

PMID- 24082555
TI  - Role of Neoadjuvant Chemotherapy (NACT) Followed by Surgical Cytoreduction in
      Advanced Epithelial Ovarian Cancer.
AB  - OBJECTIVES: To study the role of neoadjuvant chemotherapy (NACT) followed by
      surgical cytoreduction in the management of advanced epithelial ovarian cancers.
      METHODS: A prospective hospital based study of patients with advanced epithelial
      ovarian cancers (stage III and IV) was conducted at Gujarat Cancer & Research
      Institute, Ahmedabad during August 2008 to August 2010. Total 50 patients were
      treated with NACT followed by surgical cytoreduction and followed up till August
      2010. Response to NACT, optimal cytoreduction rate and overall response rate were
      analyzed. RESULTS: There were 43 patients (86%) with stage III disease and 7
      (14%) with stage IV disease. All patients were given NACT and after NACT,
      complete response occurred in 17 patients (34%), 27 (54%) had partial response.
      Optimal surgical cytoreduction could be achieved in 36(72%) of the patients. The
      median follow up was 19 months. CONCLUSIONS: NACT followed by surgical
      cytoreduction is a promising treatment strategy for the management of advanced
      epithelial ovarian cancers.

PMID- 24082556
TI  - Association of oxidative stress biomarkers and antioxidant enzymatic activity in
      male infertility of north-East India.
AB  - INTRODUCTION: Oxidative stress is a common pathology seen in approximately half
      of all infertile men. In a normal situation, the seminal plasma contains
      antioxidant mechanisms which are likely to quench these reactive oxygen species.
      However, during infertility complications these antioxidant mechanisms may
      downplay and create a situation which is called oxidative stress. OBJECTIVE: The
      aim of the present study was to assess the levels of lipid peroxide (LPO),
      protein peroxide (PPO) and activities of antioxidant enzymes superoxide dismutase
      (SOD), glutathione peroxidase (GPX) in blood and semen samples of an infertile
      male population from North-East India. METHOD: We measured LPO, PPO, SOD and GPX
      in a total of 50 infertile individuals. For the study 20 fertile donors served as
      the control group. RESULT: Patients with male factor infertility had
      significantly higher LPO and PPO levels (60.84 +/- 3.55 and 72.84 +/- 3.66; P <
      0.001) compared with controls (40.20 +/- 4.33 and 59.93 +/- 5.24) in blood. In
      semen also, the same trend was found with significantly higher LPO and PPO levels
      (200.27 +/- 6.25 and 149.80 +/- 11.47; P < 0.001) compared with controls (116.51
      +/- 5.49 and 59.10 +/- 4.62). The SOD and GPX enzymes in blood (3.40 +/- 1.06 and
      0.16 +/- 0.01; P < 0.001) and in semen (2.42 +/- 1.32 and 0.24 +/- 0.015; P <
      0.001) showed a significantly lower activity when compared with their respective
      controls (4.85 +/- 0.78; 0.36 +/- 0.05 and 4.24 +/- 0.89; 0.65 +/- 0.03). The SOD
      and GPX activity when compared with the LPO and PPO values, showed a positive
      correlation. CONCLUSION: We conclude that oxidative stress is associated with
      male factor infertility. This assessment may help in the treatment of this male
      infertility by suitable antioxidants.

PMID- 24082557
TI  - Metformin and pioglitazone in polycystic ovarian syndrome: a comparative study.
AB  - OBJECTIVES: To evaluate the effect of metformin and pioglitazone on insulin
      resistance, ovulation and hyperandrogenism in women with PCOS. METHODS: 100
      patients of age 18-30 years were included in this randomised double blind trial
      for treatment with either metformin or pioglitazone for a period of 6 months.
      RESULTS: Administration of metformin and pioglitazone for 6 months revealed that
      50 % of the patients achieved menstrual cyclicity. A decline in F-G grading for
      hirsutism within the both the groups was observed. The lipid profile also showed
      a decrease in total cholesterol, an increase in HDL-C, a decrease in VLDL-C
      levels but more so in the pioglitazone group. HOMA-IR declined more than 50-55 %
      with pioglitazone and 15 % with metformin. Thus, pioglitazone may be a better
      treatment option as far as protection from tendency to development of diabetes is
      conscerned. The rise in serum SHBG levels and decline in free androgen index and
      L/H ratio are more remarkable with pioglitazone (P < 0.05). Ovulation was
      restored in 44.2 and 56 % of patients on metformin and pioglitazone,
      respectively. CONCLUSION: Pioglitazone may be a new alternative for use in women
      with PCOS, providing more metabolic and reproductive benefits and possibly
      protection from developing diabetes and cardiovascular problem.

PMID- 24082558
TI  - Immunohistochemical Expression of Cell Proliferating Nuclear Antigen (PCNA) and
      p53 Protein in Cervical Cancer.
AB  - OBJECTIVE: This study was designed to evaluate the immunohistochemical expression
      of proliferating cell nuclear antigen (PCNA) and p53 protein expression in
      preneoplastic and neoplastic lesions in uterine cervix. STUDY DESIGN: A total of
      36 cervical biopsies were subjected for immunostaining and the results were
      correlated with different prognostic parameters. Bivariate and multivariate
      statistical analyses were done using "STATA" software. RESULTS: PCNA labeling
      index and p53 expression increased with increasing severity of CIN lesions. PCNA
      labeling index was maximum (46.0) carcinoma cervix with intense positive
      staining. In bivariate statistical analysis, p53 and PCNALI were found to be
      insignificant (0.4184 and 0.4328, respectively). Menopausal stage was
      significantly associated with CA and CIN groups (P < 0.166 and P < 0.049),
      respectively. CONCLUSION: These markers may be of greater importance in low-grade
      CIN lesions showing high proliferative index. This will place the low-grade
      lesions in higher grade indicating the utility of proliferative markers in
      decision making for intervention. This method is simple and cost effective and
      may be useful in developing countries where HPVDNA testing is still out of reach
      because of high cost.

PMID- 24082559
TI  - Evaluation of the response of concurrent high dose rate intracavitary
      brachytherapy with external beam radiotherapy in management of early stage
      carcinoma cervix.
AB  - OBJECTIVES: To evaluate local disease control and early complications of
      concomitant brachytherapy with external beam-radiotherapy in early stage
      carcinoma cervix. METHODS: Fifty patients of early stage carcinoma cervix (FIGO
      IB/IIA) were randomly divided into study group concomitant external beam
      irradiation (EBRT) and HDR-ICBT (intra-cavitary brachytherapy, xrt = 50 Gy/25 Fr,
      HDR 5.2 Gy*5 Fr) and the control group EBRT followed by HDR-ICBT (xrt = 50 Gy/25
      Fr, HDR 7.5 Gy*3 Fr). Acute reactions and local disease response were compared
      between treatment and at 6-month follow up. RESULTS: Median overall treatment
      times were 38 and 61 days in the study and the control groups, respectively.
      Acute skin reactions and diarrhea were more in the study but manageable. At the
      completion of the study, there were 80 and 68 % complete responses, 16 and 20 %
      partial responses, 0 and 8 % stable diseases in the study group and the control
      group, respectively. CONCLUSIONS: Response was better in the study group but
      statistically insignificant. Larger number of patients and longer follow up are
      required to arrive at concrete conclusion.

PMID- 24082560
TI  - A rare case of vaginal delivery after uterine rupture.

PMID- 24082561
TI  - Persistent uterine prolapse during pregnancy and labour.

PMID- 24082562
TI  - Swyer's Syndrome: In a Fifty-Year-Old Female.

PMID- 24082563
TI  - Severe adolescent menorrhagia due to cervical fibroid.

PMID- 24082564
TI  - IACDE - Milestones Crossed and the Road Ahead....

PMID- 24082565
TI  - Irrigation protocol among endodontic faculty and post-graduate students in dental
      colleges of India: A survey.
AB  - BACKGROUND: Irrigation protocol is the most critical step during the disinfection
      of an infected root canal system. AIM: The purpose of this study was to determine
      the root canal irrigation trends being practiced among the endodontic teaching
      faculty and post-graduate students in the dental colleges present in India.
      MATERIALS AND METHODS: A postal invitation to participate in this national survey
      was sent to the Department of Conservative Dentistry and Endodontic of 294 Dental
      Colleges present in India. A total of 2389 forms were successfully delivered out
      of which 794 duly filled forms were received back. Survey participants were asked
      about their irrigant selection, irrigant concentration, smear layer removal
      protocol, and use of adjuncts during irrigation. RESULTS: This survey elicited a
      positive response rate of 33.23%. Our data indicated that 92.8% of respondents
      use sodium hypochlorite (NaOCl) as the primary endodontic irrigant, with 26 gauge
      needle being most preferred for syringe irrigation, with 49.3% of them using it
      at a concentration of 2.6-4.0%. 68% of our respondents aim to remove the smear
      layer during the endodontic treatment while 47% reported using ultrasonic
      activation as an adjunct during their irrigation protocol. CONCLUSIONS: The
      findings of this survey are that the majority of teaching institutions in India
      are employing NaOCl (2.6-4.0%) as the primary endodontic irrigant. The concept of
      smear layer removal is high (68%), and there is a general trend (78%) to modify
      the irrigation protocol according to the status of the pulp, status of the
      periapex and in retreatment cases.

PMID- 24082566
TI  - Working length changes in curved canals after coronal flaring by using rotary
      files and hand file: An in vitro study.
AB  - AIM: This in vitro investigation examined the effect of early coronal flaring
      (CF) and late CF on the working length (WL) in curved root canals. BACKGROUND:
      The objective of this study was to determine if canal length is altered as a
      result of CF in curved canals of molar roots. STUDY DESIGN: The conditions
      compared were combinations of (a) stainless steel hand files using Gates Glidden
      (G. G.) drills (SS) versus nickel-titanium rotary files (Ni-Ti); and (b) early CF
      (flaring completed before WL determination) versus late CF (flaring completed
      after WL determination). Selected were 90 canals of extracted maxillary or
      mandibular first molars (mesial root of mandibular molars and the mesiobuccal
      root of the maxillary molars) from three groups. CF was accomplished for the SS
      group using G. G. drills and for the Ni-Ti group using rotary ProTaper and Hero
      Shaper files. WL was determined by a digital vernier caliper before CF,
      immediately after CF, and again after canal preparation. STATISTICAL ANALYSIS: A
      repeated measures analysis of variance (ANOVA) test and a Tukey's multiple
      prosthoc test were used for this study. RESULTS: Results indicated that WL
      decreased for all canals as a result of canal preparation. The mean decrease in
      WL was significantly greater for the SS group (-0.77 +/- 0.42 mm) than for the Ni
      Ti groups (-0.33 mm +/- 0.44). Less change in WL occurred in all groups when
      initial WL was determined after CF. CONCLUSION: WL in curved canals consistently
      decreases during the course of instrumentation. Clinician should keep this in
      mind for better treatment outcome.

PMID- 24082567
TI  - Location and dimensions of access cavity in permanent incisors, canines, and
      premolars.
AB  - BACKGROUND: Ideal access cavity assures unobstructed straight-line access to the
      apical third of the root canal and preserves tooth structure. AIM: The aim of the
      study was to determine the location and dimensions of access cavity with straight
      line access in incisors, canines, and premolars and to evaluate the largest
      diameter of their root canals in the mesiodistal and vestibulooral direction.
      MATERIALS AND METHODS: Twenty extracted teeth of each group were randomly
      selected and digitally radiographed from the mesiodistal and vestibulooral
      direction. Position of the straight-line access midline in relation to anatomical
      landmarks (incisal edges, fissures, and cusps) was recorded. The largest
      diameters in mesiodistal and vestibulooral direction were measured. Relative
      frequencies of access position and mean and standard deviation of both diameters
      were calculated. RESULTS: For the anterior teeth, the predominant location of
      straight-line access was from incisal edge, except for maxillary central
      incisors, where location was equally distributed between incisal edge and oral
      surface. In mandibular premolars, the straight-line access was positioned
      vestibular from central fissure. In mesiodistal direction, the largest diameter
      was found for maxillary central incisors and canines (1.54 mm), while the
      smallest diameter was found for mandibular incisors (0.64 mm). In vestibulooral
      direction, the largest diameter was found for maxillary first premolar (5.28 mm),
      while the smallest diameter was found for maxillary lateral incisor (1.39 mm).
      CONCLUSIONS: Knowledge of location and size of access cavity facilitates
      achieving balance between straight-line access to the apical third of the root
      canal and preservation of tooth structure.

PMID- 24082568
TI  - Comparative evaluation of the sealing ability of different obturation systems
      used over apically separated rotary nickel-titanium files: An in vitro study.
AB  - AIM: The study was designed to investigate the sealing ability of two obturation
      systems (cold laterally compacted gutta percha and Obtura II) over different
      apically separated rotary nickel-titanium files (RACE and K3 system) using dye
      extraction method. MATERIALS AND METHODS: Sixty-two mandibular premolars were
      divided into 2 groups of 30 teeth each, and 2 teeth served as negative controls.
      In Groups A and B, roots were prepared using RACE and K3 system, respectively,
      and were further subdivided into 4 subgroups. In subgroups A1, B1 and A2, B2 (n =
      10 each), files were separated at 3 mm from the tip in apical 3(rd) of the canal.
      In subgroups A3, B3 and A4, B4 (n = 5), instruments were not separated. Subgroups
      A1, A3, B1, B3 and A2, A4, B2, B4 were obturated by lateral condensation method
      and Obtura II techniques, respectively. The sealing ability of the obturated
      specimens were tested using dye extraction method. The values for each group were
      recorded and analysis of variance (ANOVA), Student "t" test (two-tailed,
      independent), and Leven's test were performed. RESULTS: Group A1 showed
      significantly less leakage than B1. No statistical significant difference between
      Groups A2 and B2 and Groups A3 and B3, respectively, were observed. Group A4
      showed significantly less leakage than B4. CONCLUSION: Groups obturated with
      Obtura II showed less leakage than the lateral condensation technique
      irrespective of presence or absence of fractured NiTi rotary system.

PMID- 24082569
TI  - The effect of amount of lost tooth structure and restorative technique on
      fracture resistance of endodontically treated premolars.
AB  - AIM: Endodontic treatment generally reduces the fracture resistance of teeth. The
      purpose of this study was to evaluate the fracture resistance and the mode of
      fracture of endodontically treated human premolars with different amounts of
      remaining tooth structure. MATERIALS AND METHODS: Seventy non-carious human
      premolars were randomly assigned into 7 groups. Group 1 (ST) did not receive any
      preparation. The teeth in groups 2-7 received root canal treatment and different
      preparations. Group 2 (MO-NF): Mesio-occlusal preparation without filling; Group
      3 (MOD-NF): Mesio-occluso-distal preparation without filling; Group 4 (MO-F):
      Mesio-occlusal preparation with direct composite restoration (Z250); Group 5 (MOD
      F): Mesio-occluso-distal preparation with direct composite restoration (Z250);
      Group 6 (CC-D): Mesio-occluso-distal preparation with cusp reduction and direct
      composite restoration (Z250); Group 7 (CC-InD): Mesio-occluso-distal preparation
      with cusp reduction and indirect composite restoration (Gradia GC). The fracture
      resistance (N) was assessed under compressive load in a universal testing machine
      (Zwick) perpendicular to the occlusal surface at a cross-head speed of 1 mm/min,
      and the mode of fracture was assessed under stereomicroscope. STATISTICAL
      ANALYSIS: Data was analyzed by Kruskal - Wallis and Mann - Whitney tests and the
      mode of fracture was analyzed by Chi-square test (P < 0.05). RESULTS: Statistical
      analysis showed that MO and MOD cavity preparations significantly reduced the
      fracture resistance of sound teeth. Direct composite restorations can improve the
      fracture resistance, and Groups 7 and 6 presented the highest fracture resistance
      values. CONCLUSIONS: Teeth with adhesive restorations showed significantly higher
      fracture resistance values as compared with the non-restored ones.

PMID- 24082570
TI  - Effects of solvent drying time on mass change of three adhesives.
AB  - AIM: Adhesives may change their mass due to water sorption or dilution of
      components after curing. The aim of this study was to evaluate the influence of
      air-drying time and water storage on mass changes (MC) of three adhesives; Adper
      Single Bond2 (ASB), One-step plus (OSP), Clearfil S(3) Bond (CSB). MATERIALS AND
      METHODS: Rectangular-shape samples from each adhesive were prepared and cured for
      120 s with a halogen light curing unit. Prior to curing, their solvent was
      evaporated by means of three different procedures depending on the passive air
      drying time (i.e., no air drying, equal to active air drying, complete
      evaporation after 3 h). Each group was further divided into two subgroups based
      on the time of water storage (1-day, 7-days), prior to measurement of MC (n =
      10). The data were analyzed using a three-way ANOVA. RESULTS: Adhesives showed
      different patterns of MC in relation to air drying and water storage; (P < 0.05).
      In OSP and CSB with increasing water storage and air drying, the MC increased
      significantly (P < 0.01). CONCLUSION: The highest MC in the etch-and-rinse
      adhesives was observed when the adhesive was not dried, while in the self-etch
      adhesive the highest changes were observed when the adhesive was completely
      dried.

PMID- 24082571
TI  - Differentiation of isolated and characterized human dental pulp stem cells and
      stem cells from human exfoliated deciduous teeth: An in vitro study.
AB  - AIMS AND OBJECTIVES: Isolation, characterization and differentiation of dental
      pulp stem cells (DPSCs) and stem cells from exfoliated human deciduous teeth
      (SHED). METHODS: The pulp tissue was digested in collagenase and cultured in DMEM
      Dulbecco's Modified Eagle's Media). The stem cells were identified and isolated.
      Surface characterization of cells was done with flow cytometer using surface
      markers. An immuno cytochemistry analysis was done. Differentiation potential was
      analyzed using various differentiation markers. RESULTS: Flow cytometry analyses
      for various CD markers showed similar results for both DPSCs and SHED. The cells
      showed positive expression for pluripotent, ectodermal and mesodermal markers.
      Cells differentiated into osteoblasts and adipocytes. CONCLUSION: The study
      demonstrated that stem cells existed in deciduous and permanent pulp tissue. The
      stem cells present in pulp tissue can be isolated, cultivated and expanded in
      vitro. Both DPSCs and SHED show almost a similar expression pattern profile for
      variety of antigens tested.

PMID- 24082572
TI  - Effect of two different chemomechanical caries removal agents on dentin
      microhardness: An in vitro study.
AB  - AIM: The aim of this in vitro study was to evaluate the effect of two different
      chemomechanical caries removal (CMCR) agents on dentin microhardness. MATERIALS
      AND METHODS: In this study, the crown portion of ten carious-free and ten caries
      affected teeth were selected. In carious-free samples, the teeth were decoronated
      at the level of cemento - enamel junction. Only the crown portion of the teeth
      was selected. Occlusal one-third of the crowns were cross-sectioned and discarded
      to expose the dentin, and it was divided into two groups, five teeth in each
      group. Then, they were further sectioned longitudinally through the centre. In
      one group, no agent was applied on one half and Carisolv was applied on other
      half. In another group, no agent was applied on one-half and Carie-Care was
      applied on the other half for 1 min. In carious samples, the crowns were
      sectioned through the centre of carious lesion. Carisolv was applied on one-half
      and Carie-Care was applied on the other half. After using CMCR agents, surface
      hardness of dentin was examined using Vickers hardness number (VHN). STATISTICAL
      ANALYSIS AND RESULTS: The data were analyzed using t-test and one-way analysis of
      variance (ANOVA). There were no significant difference among normal dentin (62.91
      +/- 2.76), Carisolv-treated normal dentin (61.72 +/- 2.89), and Carie-Care
      treated normal dentin (61.90 +/- 3.19). In carious samples, the results of
      Carisolv-treated dentin (58.57 +/- 2.62) was not statistically significantly
      different from those of the Carie-Care-treated dentin (56.77 +/- 4.41).
      CONCLUSION: In conclusion, neither of the CMCR methods caused a significant
      change in the microhardness of normal dentin and the treated carious dentin.

PMID- 24082573
TI  - Dental pulp response to collagen and pulpotec cement as pulpotomy agents in
      primary dentition: A histological study.
AB  - INTRODUCTION: As the search for a better biocompatible medicament is on, aim of
      the present study was to evaluate the pulpal response to collagen particles
      impregnated in antibiotics (Biofil-ABTM) and new commercially available cement
      (Pulpotec) that can be used as pulpal medicament. MATERIALS AND METHODS: Total
      sample of 40 teeth from 20 children in the age group of 7-10 years which are
      noncarious having bilateral retained primary teeth were enrolled for the study.
      Nine teeth each were treated with collagen particles (group I) and Pulpotec
      cement (group II), and the remaining samples were discarded due to various
      reasons. Both groups were randomly subdivided into three teeth each that were
      extracted after 7, 15, and 30 days intervals and examined histologically.
      RESULTS: Moderate to severe inflammatory cells with newly formed blood vessels
      and disorganized odontoblastic cell layer was observed in group I after all three
      intervals with dentinal bridge formation in two specimens. On contrary, none of
      the specimens in group II showed any signs of inflammation, but there was a
      discontinuity in the odontoblastic layer lining along the dentin walls.
      CONCLUSION: Both materials were proven to be promising alternatives as pulp
      medicaments. However, collagen was found to be a better material.

PMID- 24082574
TI  - Comparison of calcium hydroxide removal by self-adjusting file, EndoVac, and
      CanalBrush agitation techniques: An in vitro study.
AB  - OBJECTIVES: This study comparatively evaluated the efficacy of self-adjusting
      file (SAF), Endovac, and CanalBrush irrigant agitation protocols in removing
      calcium hydroxide (Ca(OH)2) from the root canals. MATERIALS AND METHODS: Sixty
      extracted human mandibular canine teeth were instrumented with ProTaper rotary
      instruments to size #40 and dressed with Ca(OH)2. The roots were randomly
      assigned to four groups according to irrigant agitation protocol used (n = 15).
      In Group 1: Conventional syringe irrigation (no activation, control); Group 2:
      Rotary brush agitation (CanalBrush); Group 3: Apical negative pressure irrigation
      (EndoVac system); and Group 4: Sonic agitation (SAF) were used. Scanning electron
      microscopic (SEM) evaluation was done for assessment of Ca(OH)2 removal in the
      coronal and apical thirds. Statistical analysis was performed by Wilcoxon and
      Kruskal-Wallis tests. RESULTS: There were statistically significant differences
      among the groups (P = 0.218). A statistically significant difference was seen
      between the test groups in Ca(OH)2 removal from the apical third of the canal (P
      < 0.05). In the coronal third, there was no difference between the groups (P >
      0.05). The most efficient Ca(OH)2 removal in apical third was recorded in Group 3
      (EndoVac) and Group 4 (SAF) (P < 0.05). In Group 4 (sonic agitation), there was
      no significantly difference between Ca(OH)2 removal in coronal and apical thirds.
      CONCLUSIONS: SAF and EndoVac showed significantly better performance than
      CanalBrush and conventional syringe irrigation in removing Ca(OH)2 from apical
      third of the root canals.

PMID- 24082575
TI  - Evaluation of push-out bond strength of two fiber-reinforced composite posts
      systems using two luting cements in vitro.
AB  - INTRODUCTION: The concept of using a "post" for the restoration of teeth has been
      practiced to restore the endodontically treated tooth. Metallic posts have been
      commonly used, but their delirious effects have led to the development of fiber
      reinforced materials that have overcome the limitations of metallic posts. The
      use of glass and quartz fibers was proposed as an alternative to the dark color
      of carbon fiber posts as far as esthetics was concerned. "Debonding" is the most
      common failure in fiber-reinforced composite type of posts. This study was aimed
      to compare the push-out bond strength of a self-adhesive dual-cured luting agent
      (RelyX U100) with a total etch resin luting agent (Variolink II) used to cement
      two different FRC posts. MATERIALS AND METHODS: Eighty human maxillary anterior
      single-rooted teeth were decoronated, endodontically treated, post space prepared
      and divided into four groups (n = 20); Group I: D.T. light post (RTD) and
      Variolink II (Ivoclare vivadent), Group II: D.T. light post (RTD) and RelyX U100
      (3M ESPE), Group III: Glassix post (Nordin) and Variolink II (Ivoclare vivadent)
      and Group IV: Glassix post (Nordin) and RelyX U100 (3M ESPE). Each root was
      sectioned to get slices of 2 +/- 0.05-mm thickness. Push-out tests were performed
      using a triaxial loading frame. To express bond strength in megapascals (Mpa),
      load value recorded in Newton (N) was divided by the area of the bonded
      interface. After testing the push-out strengths, the samples were analyzed under
      a stereomicroscope. RESULTS: The mean values of the push-out bond strength show
      that Group I and Group III had significantly higher values than Group II and
      Group IV. The most common mode of failure observed was adhesive between dentin
      and luting material and between post and luting material. CONCLUSIONS: The mean
      push-out bond strengths were higher for Groups I and III where Variolink II resin
      cement was used for luting the fiber post, which is based on the total etch
      adhesive approach. In most of the samples, failure was observed between cement
      dentine interface, followed by post-cement interface, which shows difficulty in
      bonding between post-cement-dentine interface.

PMID- 24082576
TI  - Evaluation of the apical sealing ability and adaptation to the dentin of two
      resin-based Sealers: An in vitro study.
AB  - AIM: To quantitatively evaluate the apical sealing ability and adaptation of two
      resin-based sealers to dentin. MATERIALS AND METHODS: Fifty freshly extracted
      mandibular first premolars were taken and sectioned at the cemento-enamel
      junction. Thirty teeth were subjected to a leakage study by the resin
      infiltration method with two groups of 10 teeth each. Group I teeth were
      obturated with methacrylate resin-based sealer (EnoRez) and Group II teeth were
      obturated with epoxy resin-based sealer (AH Plus). The remaining 10 teeth were
      used as controls (positive and negative of five teeth each). Twenty teeth were
      divided into two groups and obturated as in the leakage study and subjected to a
      scanning electronic microscopy (SEM) analysis for adaptation and resin depth
      penetration. RESULTS: Both the sealers produced apical leakage to a certain
      extent. The adaptation and resin sealer penetration in the coronal and middle
      thirds was better than in the apical third of the root canal under SEM
      observation. The hybridized resin sealer tags in the coronal and middle thirds of
      Group I were much longer than that shown by Group II. CONCLUSION: We conclude
      that the physical integrity of the sealer matrix may also be important in
      providing resistance to leakage.

PMID- 24082577
TI  - Antibacterial efficacy of Mangifera indica L. kernel and Ocimum sanctum L. leaves
      against Enterococcus faecalis dentinal biofilm.
AB  - INTRODUCTION: The Enterococcus faecalis biofilm in the root canal makes it
      difficult to be eradicated by the conventional irrigants with no toxicity to the
      tissues. Hence, plant products with least side effects are explored for their use
      as irrigants in the root canal therapy. AIM: To evaluate and compare the
      antibacterial efficacy of Mangifera indica L. kernel (mango kernel) and Ocimum
      sanctum L. leaves (tulsi) extracts with conventional irrigants (5% sodium
      hypochlorite (NaOCl) and 2% chlorhexidine) against E. faecalis dentinal biofilm.
      MATERIALS AND METHODS: Agar diffusion and broth microdilution assay was performed
      with the herbal extracts and conventional irrigants (2% chlorhexidine and 5%
      NaOCl) against E. faecalis planktonic cells. The assay was extended onto 3 week
      E. faecalis dentinal biofilm. RESULTS: Significant reduction of colony forming
      units (CFU)/mL was observed for the herbal groups and the antibacterial activity
      of the herbal groups was at par with 5% NaOCl. CONCLUSIONS: The antibacterial
      activity of these herbal extracts is found to be comparable with that of
      conventional irrigants both on the biofilm and planktonic counterparts.

PMID- 24082578
TI  - An in vitro stereomicroscopic comparative evaluation of a combination of apex
      locator and endodontic motor with an integrated endodontic motor.
AB  - OBJECTIVE: To compare the efficacy of an integrated apex locator and an apex
      locator and endodontic motor assembly in maintaining the working length when
      operated under autoreverse mode. STUDY DESIGN: Thirty distobuccal roots of intact
      maxillary first molars were taken and access cavities were prepared. The teeth
      were divided into Group I: Prepared with TCM Endo V and Group II: Prepared with
      ProPex and NSK assembly. The instrumentation was ended in ProTaper F3 file, which
      was cemented in the canal. The roots were sectioned, observed under a
      stereomicroscope and the distance from instrument tip to the apical foramen was
      measured. RESULTS: Mean difference in the deviation of two groups was 0.075 mm, P
      = 0.34 (>0.05) which was statistically insignificant when assessed with unpaired
      t-test. CONCLUSION: The assembly of ProPex-NSK Endo-mate DT and the apex locating
      endomotor TCM Endo V Nouvag are clinically acceptable.

PMID- 24082579
TI  - Comparative evaluation of push-out bond strength of ProRoot MTA, Biodentine, and
      MTA Plus in furcation perforation repair.
AB  - PURPOSE: Few studies have comparatively evaluated the push-out bond strength of
      different calcium silicate-based materials (CSMs) used in furcal perforation
      repair. The objective of this in vitro study was to comparatively evaluate the
      push-out bond strength of commercially available CSMs used as furcation repair
      materials, in the presence of blood contamination. MATERIALS AND METHODS: Furcal
      perforations were made in 120 molars and were divided on the basis of the repair
      material used (ProRoot MTA, Biodentine, and MTA Plus), blood contamination, and
      duration of setting time (24 h vs. 7 days). Push-out bond strength was measured
      and analyzed by three-way analysis of variance (ANOVA) test. RESULTS: Push-out
      bond strength increased with time. The 24-h push-out strength of MTA was less
      than that of Biodentine. Blood contamination affected the push-out bond strength
      of MTA Plus irrespective of the setting time. CONCLUSION: Caution should be taken
      while condensing restorative materials over furcation repair materials.

PMID- 24082580
TI  - Comparative evaluation of the antibacterial effects of four dentine bonding
      systems: An in vitro study.
AB  - AIM: The aim of this in vitro study was to evaluate and the compare antibacterial
      efficacy of four dentin bonding system against Streptococcus mutans,
      Streptococcus salivarius and Lactobacillus acidophilus over a period of three
      months using agar disk diffusion test. METHODOLOGY: All the three standard
      bacterial strains were inoculated into BHI broth and incubated at 37 degrees C
      for 48 hours. A 100 MUl of broth suspension containing aliquots of S. mutans, S.
      salivarius and L. acidophilus were spread onto M-H agar medium using sterile
      cotton swabs. The experimental groups were as follows: GROUP A: Test conducted
      for evaluation of antimicrobial efficacy against S. mutans MTCC 497, GROUP B:
      Test conducted for evaluation of antimicrobial efficacy against S. salivarius
      MTCC 1938, and GROUP C: Test conducted for evaluation of antimicrobial efficacy
      against L. acidophilus MTCC 447. For sample preparation, 20 MUl bonding agent was
      dropped with micropipettes on paper disks, and blown dry for 10 seconds. Then it
      was light-cured at 2 mm for 20 sec using a QTH visible light curing unit. For
      first reading, the sample disks were placed over the freshly inoculated agar
      plates and then incubated at 37 degrees C for 48 hours. The rest of the paper
      disks were stored in dark, submerged in distilled water at 37 degrees C. They
      were placed on freshly inoculated spread plates after specific time intervals- 1
      day, 1 week, 2 weeks, 1 month and 3 months after ageing in PBS. After incubation,
      the diameters of zones of inhibition around the plates were measured. The
      experiment was performed twice in triplicate. The data was then statistically
      analysed using Two way ANOVA test and post hoc. RESULTS: Results showed that Xeno
      III had the maximum antibacterial efficacy over a period of three months,
      followed by XP bond. This antibacterial activity was maximum against
      Streptococcus mutans, followed by Lactobacillus acidophilus and least against
      Streptococcus salivarius. Adper Easy One and G bond had minimal effect against
      the test bacteria during the test period. CONCLUSION: The antibacterial effect
      decreased over a period of three months for all the dentin bonding systems.

PMID- 24082581
TI  - Management of mandibular first molar with four canals in mesial root.
AB  - Successful root canal treatment depends on adequate cleaning, shaping, and
      filling of the root canal system. The presence of middle mesial (MM) root canal
      of mandibular molars has been reported by various authors. But incidence of four
      canals in mesial root of mandibular molar is very rare. The aim of this case
      report is to present and describe the identification and management of a
      mandibular first molar with four canals in the mesial root and single canal in
      the distal root. 

PMID- 24082582
TI  - Endodontic management of an unusual foreign body in a maxillary central incisor.
AB  - The discovery of foreign bodies in the teeth is often diagnosed accidentally. It
      is commonly seen in children. These foreign objects may act as a potential source
      of infection and may later lead to a painful condition. Detailed case history,
      clinical and radiographic examinations are necessary to come to a conclusion
      about the nature, size, and location of the foreign body, and the difficulty
      involved in its retrieval. This paper discusses the types of foreign objects
      found in and around the teeth and reports an unusual case of a stapler pin in the
      root canal of a tooth, its retrieval, and associated management of the involved
      teeth. 

PMID- 24082584
TI  - The 2nd ECCLIRES convention (Endodontics and Conservative dentistry CLInical
      RESearch).

PMID- 24082583
TI  - Endodontic treatment of hypertaurodontism with multiple bilateral taurodontism.
AB  - The term taurodontism is derived from the Latin word tauros, for "bull," and the
      Greek term odus, for "tooth," or "bull tooth." Taurodontism is a morpho
      anatomical developmental anomaly, which is seen infrequently in teeth only. It is
      characterized by a deficiency in the constriction at the cement-enamel junction,
      with lengthened pulp chambers and apical displacement of the pulpal floor. This
      gives the tooth a quadrilateral or cylindrical look. This report presents a case
      of multiple bilateral taurodontism and the successful endodontic treatment of the
      tooth that had hypertaurodontism. A male patient was referred to the endodontic
      clinic with decayed left maxillary first molar. Hypertaurodontism was confirmed
      after clinical and radiographic examination. Panaromic X-rays revealed that all
      of the patient's molar teeth were taurodontic. Taurodontism offers challenges to
      the practitioner during shaping and disinfection and at the time of filling the
      root canals. 

PMID- 24082585
TI  - Approach to trauma care in the armed forces.

PMID- 24082586
TI  - Efficacy of low level laser therapy on wound healing in patients with chronic
      diabetic foot ulcers-a randomised control trial.
AB  - Foot ulcers are serious complications of Diabetes Mellitus (DM) and are known to
      be resistant to conventional treatment. They may herald severe complications if
      not treated wisely. Electromagnetic radiations in the form of photons are
      delivered to the ulcers in laser form to stimulate healing. This study was
      conducted to evaluate the efficacy of Low Level Laser Therapy (LLLT) in diabetic
      ulcer healing dynamics. To determine mean percentage reduction of wound area in
      study and control groups. SETTINGS: KLES Dr. Prabhakar Kore Hospital and Medical
      Research Centre, Belgaum. STUDY DESIGN: Randomized-Control Study. METHODS: A
      total of 68 patients with Type 2 DM having Meggitt-Wagner Grade I foot ulcers of
      atleast more than 4 weeks duration, less than 6 * 6 cm(2) with negative culture
      were studied. Patients were randomized into two groups of 34 each. Patients in
      study group received LLLT with conventional therapy and those in control group
      were treated with conventional therapy alone. Healing or percentage reduction in
      ulcer area over a period of 15 days after commencement of treatment was recorded.
      STATISTICAL ANALYSIS: Unpaired Student T Test and Mann Whitney U test. Mean age
      of the patients was 50.94 years in control group and 54.35 years in study group
      (p = 0.065). There was no significant difference between control and study group
      with respect to mean FBS and HbA1c levels (p > 0.05), suggesting no biochemical
      differences between two groups. Initial ulcer area was 2608.03 mm(2) in study
      group and 2747.17 mm(2) in control group (p = 0.361). Final ulcer area was
      1564.79 mm(2) in study group and 2424.75 mm(2) in control group (p = 0.361).
      Percentage ulcer area reduction was 40.24 +/- 6.30 mm(2) in study group and 11.87
      +/- 4.28 mm(2) in control group (p < 0.001, Z = 7.08). Low Level Laser Therapy is
      beneficial as an adjunct to conventional therapy in the treatment of diabetic
      foot ulcers (DFU).

PMID- 24082587
TI  - V-y advancement flap technique in resurfacing postexcisional defect in cases with
      pilonidal sinus disease-study of 25 cases.
AB  - We report our experience of technique of V-Y-plasty in treatment of pilonidal
      sinus. A retrospective study of 25 patients performed from 2005 to 2010 at
      Deenanath Mangeshkar Hospital and Sassoon General Hospitals, Pune, was performed.
      The unilateral or bilateral V-Y advancement flap technique was used in the
      management of these patients. The outcome was assessed on the basis of efficacy
      of flap surgery in achieving wound healing and recurrence. The follow-up ranged
      from 6 months to 5 years. The study included 25 cases of pilonidal sinus.
      Nineteen patients (76%) underwent unilateral V-Y-plasty and six patients (24%)
      underwent bilateral V-Y-plasty. Eighty-four percent cases were from the age group
      of 21-30 years. Sixty-eight percent patients were mobilized on the fourth
      postoperative day and 32% patients were mobilized on the third postoperative day.
      No recurrence was found in any of the patients. Itching and hypertrophic scar
      were found in two cases (8%), and decreased sensation was found in one patient
      (4%). The V-Y advancement flap technique for the treatment of pilonidal sinus is
      efficient and can reduce recurrence. Unilateral/bilateral V-Y flap achieves
      suture line away from midline, obliteration of natal fold and coverage of defect
      without tension. In follow-up none of the patients showed recurrence. This
      technique has distinctly less morbidity and avoids of multiple dressings,
      reducing the total cost of the treatment. V-Y advancement flap is distinctly
      better choice among the available flaps as it is less time-consuming, requires
      less technical expertise as compared to Z-plasty and perforator flaps, and is
      reliable and easy to plan. 

PMID- 24082588
TI  - Peripheral and cranial nerve sheath tumors-a clinical spectrum.
AB  - To analyze the incidence of nerve sheath tumors in a tertiary care hospital over
      a period of 5 years and review the literature. Medical case records from last 5
      years were retrieved and histopathology and operative details were studied in a
      retrospective analysis. There is a slight male preponderance when it comes to
      nerve sheath tumors and acoustic schwannomas accounted for the largest fraction
      among schwannomas. Nerve sheath tumors include a wide spectrum of schwannomas,
      neurofibromas and malignant peripheral nerve sheath tumors. Hence combination of
      clinical, pathological and surgical expertise is needed to diagnose accurately. 

PMID- 24082589
TI  - The role of nasogastric intubation on postoperative gastrointestinal function in
      patients with obstructive jaundice.
AB  - It is the practice of many surgeons to use the routine nasogastric tube after
      biliary operations, but its usefulness has been questioned. This study was
      designed to determine the effect of postoperative nasogastric intubation on
      gastrointestinal function in patients with obstructive jaundice. In this
      randomized clinical trial, 40 patients who underwent choledochoduodenostomy or
      hepaticojejunostomy were randomly divided into two groups. Patients in the
      experimental group did not have the nasogastric tube, and in the control group
      the nasogastric tube was routinely applied after surgery. Gastrointestinal
      function was compared in these two groups. Patients with no nasogastric
      intubation did not show any postoperative complications or prolonged hospital
      stay. On the contrary, nasogastric tube insertion postponed return of bowel
      function and increased the incidence of nausea and vomiting, while it did not
      affect the incidence of postoperative ileus. Routine use of the nasogastric tube
      after choledochoduodenostomy or hepaticojejunostomy can delay normal
      gastrointestinal function and increase postoperative discomfort. 

PMID- 24082590
TI  - Delorme's Procedure for Full-Thickness Rectal Prolapse; Does it Alter Anorectal
      Function.
AB  - Clinical and anorectal manometric results of Delorme's procedure for full
      thickness rectal prolapse were assessed retrospectively. Thirty-seven patients
      with full-thickness rectal prolapse who were operated on with Delorme's procedure
      were included in the study. They were 11 males and 26 females with mean age of 54
      +/- 4.4 years (range 15-70 years) and mean follow-up period of 27 +/- 4.6 months
      (15-48 months). The mean operative time was 65 +/- 4.5 min (60-90 min); there was
      no mortality and blood loss was minimal. Mean hospital stay was 3.5 days (2-6
      days). Outcomes of the procedure were satisfactory in 29 patients (78.4%).
      Dissatisfaction came from recurrence and persistence of fecal incontinence.
      Prolapse recurrence had been observed in six patients; three of them were treated
      by the same technique and showed no recurrence, and the others were treated by
      either mucosal resection (1) or abdominal resection rectopexy (2). Constipated
      patients showed improved symptoms in 7 of 10 cases. Of 11 patients who were
      incontinent preoperatively, seven patients became fully continent.
      Postoperatively, anorectal manometric studies (MRP, MSP, MTV, and UDV) showed
      significant improvement in all patients with intact RAIR. Delorme's operation,
      coupled with avoidance of abdominal procedures, is the treatment of choice of
      rectal prolapse in elderly frail patients and in patients with defecatory
      disorders. 

PMID- 24082591
TI  - A prospective series case study of pyogenic liver abscess: recent trands in
      etiology and management.
AB  - Our study aims to review the literature on the management of pyogenic liver
      abscess, focusing on the choice of drainage. A case series of our experience with
      clinicopathological correlation is presented to highlight the indication and
      outcome of each modality of drainage. Intravenous antibiotic is the first line,
      and mainstay, of treatment. Drainage is necessary for large abscesses, equal to
      or larger than 5 cm in size, to facilitate resolution. While percutaneous
      drainage is appropriate as first-line surgical treatment in most cases, open
      surgical drainage is prudent in cases of rupture, multiloculation, associated
      biliary, or intra-abdominal pathology. Percutaneous drainage may help to optimize
      clinical condition prior to surgery. Nevertheless, in current good clinical
      practices, the choice of therapy needs to be individualized according to
      patient's clinical status and abscess factors. They are complementary in the
      management of liver abscesses. 

PMID- 24082592
TI  - Morgagni-larrey hernia- a review of 20 cases.
AB  - Morgagni-Larrey hernia is an uncommon entity. The majority of the literature
      describes hernia occurring mostly on the right side, a few on the left side and
      rarely bilateral. Retrospective chart review was done for the patients with the
      diagnosis of adult diaphragmatic hernia from January 1997 to December 2010. Post
      operative course was evaluated for outcome, morbidity and mortality. Out of 20
      patients, 13 (65 %) were males and 7 (35 %) were females. Their age ranged from
      17 to 50 years (mean = 29.6). Abdominal discomfort was the most common
      presentation. Eight patients (40 %) were asymptomatic at presentation. Plain X
      Ray chest was done for all. Ten patients (50 %) underwent suture repair, 6 (30 %)
      had mesh placement and the other 4 (25 %) underwent both: suture repair
      buttressed with mesh. Volvulus of stomach was noted in 5 (25 %) cases. All
      patients had left sided hernia. There was insignificant morbidity and no
      mortality. There was no recurrence in 16 patients followed up for a mean duration
      of 20 months (range = 8 to 32 months). In Morgagni-Larrey hernia, abdominal
      approach gives good accessibility to reduce the hernia and to undertake repair.
      When complicated with incarceration, perforation, gangrene or volvulus of the
      herniated bowel; this can be dealt with ease. Plain X Ray of the chest is fairly
      accurate in suggesting the diagnosis of Morgagni-Larrey hernia. 

PMID- 24082593
TI  - Ischemic colitis.
AB  - Ischemic diseases of the gastrointestinal tract are some of the commonly
      encountered gastrointestinal diseases which are difficult to diagnose and still
      more difficult to treat. Presentation of colon ischemia is even more subtle, and
      this review article details about the various presentation patterns of ischemic
      colitis and their management. 

PMID- 24082595
TI  - Very important person syndrome: a psychosocial problem!

PMID- 24082594
TI  - Diagnosis and management of choledochal cysts.
AB  - Choledochal cysts are rare disease and of unknown etiology. These are typically a
      surgical problem of infancy and childhood, but in nearly 20 % of the patients the
      diagnosis is delayed until adulthood. The presentation and therapeutic strategies
      for choledochal cysts in adult may differ from that of childhood. The surgical
      management of choledochal cysts in adults is complicated by associated
      hepatobiliary pathology. Despite the absence of clinical trials, a consensus for
      the management of choledochal cysts is excision. This review examines the
      spectrum of hepatobiliary pathology encountered with choledochal cysts and the
      surgical alternatives for managing choledochal cysts based on review of relevant
      literature in English language indexed on MEDLINE. 

PMID- 24082596
TI  - Review article: a critique.

PMID- 24082597
TI  - A modified posterior pelvic exenteration technique in a woman: (a simplified
      method with using transvaginal way).
AB  - We represent a simplified surgical method for posterior pelvic exenteration in a
      woman by using the transvaginal way in addition to classic abdominal approach. A
      modified posterior pelvic exenteration technique was performed in a patient with
      bulky pelvic tumor. The transvaginal way was used for the deep perineal
      dissection when the abdominal dissection was arrested. An ultralow coloanal
      anastomosis was completed by using the transvaginal way. After the recovery
      period, the patient was discharged from hospital without any complication. The
      transvaginal access should be reminded in the circumstances of the abdominal
      dissection arrested in posterior pelvic exenteration operations in women. 

PMID- 24082598
TI  - Transanal Suture Rectopexy for Haemorrhoids: Chivate's Painless Cure for Piles.
AB  - The aim of the study was to evaluate Chivate's new procedure of transanal suture
      rectopexy for haemorroids for pain, bleeding, hospital stay, recurrence and
      complications. During the period between January 2006 and December 2008, the
      procedure was used for 166 cases symptomatic of grade II, III and IV
      haemorrhoids, at six different institutes by five different colorectal surgeons.
      In the series, 92 cases were males and 74 cases were females; average age was
      49.5 years; youngest patient was 23 years of age and eldest was of 82 years of
      age. According to the gradation, II-52 cases, III-86 cases and IV-28 cases were
      enrolled for the procedure. The piles mass was reduced by head low and manually.
      The mucosa and submucosa were transfixed to muscle of the rectum by 0.5-1.0 cm
      long stitches. Similar stitching was continued all along the complete
      circumference of the rectum, 2 and 4 cm distal to the dentate line. In all cases,
      antibiotics and anti-inflammatory medicines were prescribed for 5 days. No pain
      was noticed in 162 cases; in 4 cases a pain dull in nature was described by the
      patients. All the 166 cases were discharged after 24 h. Intraoperative bleeding
      from the suture line was observed in 15 cases, which required temporary
      compression. On proctoscopy, in 3 cases intra-anal grade I, protrusion of piles
      cushion without bleeding was noticed. No incontinence, no recurrent bleeding, no
      frequency of stool, or no tenusmus was observed. In 2 cases, 6 months after
      operation, residual external piles were observed, which required excision. The
      procedure requires no special costly instruments or any disposables. Patients
      require short stay for 24 h. The procedure is a painless cure for haemorrhoids. 

PMID- 24082599
TI  - Primary chondrosarcoma of male breast: a rare case.
AB  - Sarcomas of the breast are relatively rare and account for 1% of all primary
      malignant tumors of the breast. Pure and primary chondrosarcoma of the male
      breast is an extremely rare tumor. It may arise either from the breast stroma
      itself or from underlying bone or cartilage. Differential diagnoses include
      cystosarcoma phyllodes and breast metaplastic carcinoma with chondroid
      differentiation. 

PMID- 24082600
TI  - Synchronous tricompartmental benign CNS tumors with tonsillar herniation,
      cervicodorsal syringomyelia and hydrocephalus.
AB  - In this study, three primary central nervous system tumors of different
      histological cell types occurring together without neurofibromatosis are
      reported. These included a sellar pituitary adenoma with apoplexy, a large
      torculo-tentorial meningioma in the posterior fossa, and a cervical spinal
      intramedullary schwannoma. Displacement of primitive multipotent cells in
      different central nervous system compartments or the oncogenic effects of
      activated signaling of growth factor receptors are the proposed
      pathophysiological mechanisms for the simultaneous genesis of different types of
      tumors. There was associated tonsillar herniation, cervicodorsal syringomyelia,
      and hydrocephalus. The radiological features and treatment strategy of these rare
      synchronous tumors are highlighted. 

PMID- 24082601
TI  - Familial isolated hyperparathyroidism: role of intra operative parathormone
      assay.
AB  - Primary Hyperparathyroidism (PHPT) has been reported to occur in members of same
      family either alone or in syndromic association. We report a family of patients
      with multi glandular disease wherein we have successfully used intra operative
      PTH (IOPTH) to assess the completeness of resection. Three members of one family
      were affected (One male and two females). Two of them had symptomatic disease
      whereas one was asymptomatic. Since the genetic studies are not available we used
      a combination of radiological, clinical and laboratory findings to rule out the
      other components of MEN syndromes. Extent of surgery in familial isolated
      hyperparathyroidism (FIHP) is controversial. Hence for confirmation of adequate
      parathyroid tissue resection we used IOPTH. Role of IOPTH has been well
      established in sporadic PHPT but controversial in multi glandular syndromes.
      IOPTH was successfully used to confirm the excision and establish cure. 

PMID- 24082602
TI  - Giant liposarcoma of the omentum mimicking an ovarian tumor. A case report.
AB  - Liposarcomas are common soft tissue of the retroperitoneum and the limbs. They
      are rarely found in the greater omentum. Once in the peritoneum, these can become
      enormous and can be mistaken for ovarian mass. The authors report a case of giant
      omental liposarcoma revealed by an abdominal mass and genital prolapse due to the
      compression syndrome. A complete macroscopic resection of the omental tumour was
      performed. A post operative chemotherapy was also prescribed. A description of
      this clinical presentation in the preoperative assessment, the characteristics of
      this tumour, together with the use of adjuvant chemotherapy are discussed in this
      report. 

PMID- 24082603
TI  - Retroperitoneal Mass-lymphangiomyoma.
AB  - We report a case of retroperitoneal mass, in a postmenopausal lady,about a size
      10-8 cm in left side of abdomen. This turned out pathologically lymphangio-myoma.
      Retrospectively when we searched in literature we found that, commonly
      lymphangiomyoma seen in premenopausal women and is associated with ascites or
      renal angiomyolipoma or plural effusion. But in our case CxR -PA was normal and
      abdominal USG was not showing renal or ovarian involvement. It was a rare case
      and presentation was rare than the literature. 

PMID- 24082604
TI  - Transthoracic repair of asymptomatic morgagni hernia in an adult.
AB  - Morgagni hernia represents a rare type of diaphragmatic hernia which usually
      occurs on the right side, in the anterior mediastinum. Predisposing factors of
      Morgagni hernia include pregnancy, obesity or other causes of increased
      intraabdominal pressure, and a history of trauma. Most of adults diagnosed with a
      foramen of Morgagni are asymptomatic. We report a case of an overweight 23-year
      old asymptomatic patient with a Morgagni hernia incidentally diagnosed on chest x
      ray. There was a satisfactory result after the repair by a transthoracic
      approach. 

PMID- 24082605
TI  - Spontaneous rupture of a giant hepatic hemangioma-report of a case.
AB  - Hemangioma is the commonest benign hepatic neoplasm. Most cases are asymptomatic.
      Spontaneous rupture is rare (1-4%). Only 34 cases have been reported in adults.
      None had history of trauma. We report a case, the first from India of spontaneous
      rupture of a giant hepatic hemangioma, in a 25 year old male presenting with
      acute abdomen. He underwent right hepatectomy. Histopathology suggested cavernous
      hemangioma. 

PMID- 24082606
TI  - Superbugs and we intensivists: A time for introspection....

PMID- 24082607
TI  - Catheter related blood stream infection in Indian PICUs: Several unanswered
      issues!

PMID- 24082608
TI  - Carbapenem-resistant Acinetobacter ventilator-associated pneumonia: Clinical
      characteristics and outcome.
AB  - OBJECTIVE: To study the clinical characteristics and 28-days mortality in
      patients with ventilator-associated pneumonia (VAP) due to carbapenem-resistant
      Acinetobacter (CRA). DESIGN: Retrospective, observational, cohort study. SETTING:
      Intensive care unit (ICU) of a university hospital. MATERIALS AND METHODS:
      Microbiologically confirmed VAP due to CRA infection. INTERVENTION: None.
      RESULTS: Out of 87 patients with VAP due to CRA, 60 (69%) were male; whose median
      age was 51 years; 73 (84%) patients were medical; 26 (30%) had history of
      hospitalization in last 3 months; median acute physiology and chronic health
      evaluation (APACHE) II was 15 and median SOFA 9 at admission; primary reason for
      ICU admission was respiratory failure (34%); 46 (53%) patients had more than 2
      organ failure at ICU admission; median length of ICU stay was 19 days; 66 (76%)
      patients need vasoactive agents during ICU stay, whereas 55 (63%) patients had
      renal failure; median duration of mechanical ventilation was 17 days; 22 (25%)
      patients had acute respiratory distress syndrome (ARDS) during ICU stay; 72 (83%)
      patients had exposure to carbapenem before inclusion in the study; 33 (38%)
      patients had same organism at other sites. In the follow-up, 47 (54%) patient
      survived at 28 days after having VAP; whereas only 40 (46%) patients were
      discharged from the hospital. CONCLUSIONS: CRA-VAP has high crude mortality.
      Advanced age; severity of illness and presence of pneumonia at ICU admission; and
      presence of shock, ARDS and renal failure have impact on outcome in these
      patients.

PMID- 24082609
TI  - Catheter related blood stream infections in the paediatric intensive care unit: A
      descriptive study.
AB  - CONTEXT: Catheter related blood stream infections (CRBSI) contributes
      significantly to morbidity, mortality and costs in intensive care unit (ICU). The
      patient profile, infrastructure and resources in ICU are different in the
      developing world as compared to western countries. Studies regarding CRBSI from
      pediatric intensive care unit (PICU) are scanty in the Indian literature. AIMS:
      To determine the frequency and risk factors of CRBSI in children admitted to
      PICU. SETTINGS AND DESIGN: Descriptive study done in the PICU of a tertiary care
      teaching hospital over a period of four months. MATERIALS AND METHODS: Study
      children were followed up from the time of catheterization till discharge. Their
      clinical and treatment details were recorded and blood culture was done every 72
      h, starting at 48 h after catheterization. The adherence of doctors to Centre for
      Disease Control (CDC) guidelines for catheter insertion was assessed using a
      checklist. STATISTICAL ANALYSIS: Clinical parameters were compared between
      colonized and non-colonized subjects and between patients with and without CRBSI.
      Unpaired t-test and Chi-square test were used to test the significance of
      observed differences. RESULTS: Out of the 41 children, 21 developed colonization
      of their central venous catheter (66.24/1000 catheter days), and two developed
      CRBSI (6.3/1000 catheter days). Infants had a higher risk for developing
      colonization (P = 0.01). There was 85% adherence to CDC guidelines for catheter
      insertion. CONCLUSIONS: The incidence of CRBSI and catheter colonization is high
      in our in spite of good catheter insertion practices. Hence further studies to
      establish the role of adherence to catheter maintenance practices in reducing
      risk of CRBSI is required. The role of a composite package of interventions
      including insertion and maintenance bundles specifically targeting infants needs
      to be studied to bring down the catheter colonization as well as CRBSI rates.

PMID- 24082610
TI  - Infective endocarditis in an Indian setup: Are we entering the 'modern' era?
AB  - BACKGROUND: The clinical profile of infective endocarditis (IE) has been
      continuously evolving over last 3-4 decades as highlighted by many studies from
      developed world. OBJECTIVES: To evaluate the recent changes in the spectrum and
      clinical profile, and outcome of IE in an Indian setup. MATERIALS AND METHODS:
      This was a descriptive, cross-sectional study. Demographic, clinical,
      characteristics, treatment, and outcome were examined in 'definite' cases of IE
      admitted at our institute between July 2005 and December 2010. RESULTS: 61
      'definite' cases were identified. Mean patient age was 49.3 +/- 13.7 years. Male
      to female ratio was 3.3:1. Rheumatic heart disease was the underlying heart
      disease in 23 (37.7%) patients. 33 (54.1%) patients had already received
      antibiotic therapy before presentation to us. Blood cultures were positive in 41
      (67.2%) patients. Streptococci and staphylococci were the commonest microbial
      isolates, 9 (21.4%) patients each. Transesophageal echocardiography (TEE) was
      done for all the patients. Vegetations were detected in 54 (88%) patients.
      Surgery was done in 30 (49.2%) patients. In-hospital mortality happened in 4
      (6.5%) patients. CONCLUSIONS: WE RECORDED SEVERAL NEW TRENDS, LIKE: 1) an
      increasing age, 2) an increasing proportion of patients with no previously known
      heart disease, 3) improving culture positivity rates, 4) rise in staphylococcal
      infections, 5) increased usage of TEE, 6) high elective surgical rate, and 7)
      apparent improved survival rates. These changes point to the fact that 'modern
      era' changes in the profile of IE have started to appear in a selected population
      in India.

PMID- 24082611
TI  - Mild carbon monoxide poisoning impairs left ventricular diastolic function.
AB  - RATIONALE: Carbon monoxide (CO) poisoning is associated with direct
      cardiovascular toxicity. In mild CO poisoning in which cardiovascular life
      support is not required, the effects of CO on left and right ventricular
      functions are unknown in patients without cardiac failure. OBJECTIVES:
      Echocardiography was used to determine whether or not mild CO poisoning impairs
      ventricular function. Twenty otherwise healthy patients with CO poisoning and 20
      age- and gender-matched controls were studied. Echocardiographic examinations
      were performed at the time of admission and 1 week after poisoning. RESULTS: The
      impairment observed in the left and right ventricular diastolic function at the
      time of admission was greater than the impairment 1 week after poisoning. Mild CO
      poisoning did not have a significant effect on systolic function.
      Carboxyhemoglobin levels were positively correlated with left ventricular
      diastolic dysfunction, whereas the levels were not correlated with right
      ventricular diastolic function. CONCLUSIONS: In CO intoxication, the development
      of left and right ventricular diastolic dysfunction precedes systolic
      abnormality. Patients with mild CO poisoning do not manifest cardiovascular
      symptoms; however, it should be borne in mind that most of these patients have
      myocardial involvement.

PMID- 24082612
TI  - Ketamine in status asthmaticus: A review.
AB  - BACKGROUND AND AIMS: Status asthmaticus is a common cause of morbidity and
      mortality. The addition of ketamine to the standard treatment regimen of severe
      asthma has shown to improve outcome and alleviate the need for mechanical
      ventilation. The purpose of this review is to determine the pulmonary effects of
      ketamine and to determine whether sufficient evidence exists to support its use
      for refractory status asthmaticus. DATA SOURCE: MEDLINE, EMBASE, Google Scholar,
      and Cochrane data bases (from their inception to Jan 2012) using key words
      "ketamine", "asthma", "bronchospasm", "bronchodilator", and "mechanical
      ventilation" were searched to identify the reports on the use of ketamine as a
      bronchodilator in acute severe asthma or status asthmaticus, and manual review of
      article bibliographies was done. Relevant databases were searched for the ongoing
      trials on use of ketamine as a bronchodilator. Outcome measures were analyzed
      using following clinical questions: Indication, dose and duration of ketamine
      use, main effects on respiratory mechanics, adverse effects, and mortality.
      RESULTS: Twenty reports illustrating the use of ketamine as a bronchodilator were
      identified. In total, 244 patients aged 5 months to 70 years received ketamine
      for bronchospasm. Twelve case reports, 3 double-blind randomized placebo
      controlled trials, 2 prospective observational studies, 2 clinical evaluation
      study, and 1 retrospective chart review were retrieved. Most of the studies
      showed improved outcome with use of ketamine in acute severe asthma unresponsive
      to conventional treatment. Patients who received ketamine improved clinically,
      had lower oxygen requirements, and obviated the need for invasive ventilation.
      Mechanically-ventilated patients for severe bronchospasm showed reduction in peak
      inspiratory pressures, improved gas exchange, dynamic compliance and minute
      ventilation, and could be weaned off successfully following introduction of
      ketamine. CONCLUSION: In various studies, ketamine has been found to be a
      potential bronchodilator in severe asthma. However, a large prospective clinical
      trial is warranted before laying down any definitive recommendations on its use
      in status asthmaticus.

PMID- 24082613
TI  - Sepsis induced immunosuppression: Implications for secondary infections and
      complications.
AB  - Sepsis is the commonest cause of admission to medical ICUs across the world.
      Mortality from sepsis continues to be high. Besides shock and multi-organ
      dysfunction occurring following the intense inflammatory reaction to sepsis,
      complications arising from sepsis-related immunoparalysis contribute to the
      morbidity and mortality from sepsis. This review explores the basis for sepsis
      related immune dysfunction and discusses its clinical implications for the
      treating intensivist. Recent trends indicate that a significant proportion of
      septic patients succumb to the complications of secondary infections and chronic
      critical care illness from the initial bout of sepsis. Therefore care-givers in
      the ICU need to be aware of the impediments posed by sepsis-related immune
      dysfunction that can impair recovery in patients with sepsis and contribute to
      sepsis-related mortality. 

PMID- 24082614
TI  - Prevalence of malnutrition in a tertiary care hospital in India.
AB  - INTRODUCTION: Malnutrition adversely affects clinical outcome of hospitalized
      patients. This observational prospective study was done to assess the prevalence
      of malnutrition and its grade among patients admitted in a mixed intensive care
      unit (ICU) of a tertiary care hospital in order to help devise a comprehensive
      nutrition program for the malnourished. MATERIALS AND METHODS: A total of 500
      sequential patients admitted to the ICU were screened on admission over a year
      period for malnutrition using the Subjective Global Nutritional Assessment (SGNA)
      score. Distribution of the degree of malnutrition according to co-morbidities was
      also documented. RESULTS: Of the total, 198 (39.6%) patients were malnourished,
      including one patient qualifying as severely malnourished; 68% patients were
      male, however, there was no statistically significant difference between
      nutrition status between sexes. Hypertension, diabetes, and cancer were the three
      most commonly encountered co-morbidities among the malnourished. A total of 86%
      of all cancer patients admitted were malnourished against only 12% of trauma
      patients. CONCLUSION: This study showed that almost two-fifth of the patients
      admitted were malnourished in this tertiary care hospital and that there is an
      urgent need to develop a comprehensive nutritional care program in many such
      Indian ICUs.

PMID- 24082615
TI  - Elevated procalcitonin is associated with increased mortality in patients with
      scrub typhus infection needing intensive care admission.
AB  - CONTEXT: Procalcitonin is a biomarker of bacterial sepsis. It is unclear if scrub
      typhus, a rickettsial illness, is associated with elevated procalcitonin levels.
      AIM: To assess if scrub typhus infection is associated with high procalcitonin
      levels and whether high levels portend a poorer prognosis. SETTING AND DESIGN:
      Retrospective study of patients with severe scrub typhus infection, admitted to
      the medical intensive care unit of a tertiary care university affiliated teaching
      hospital. MATERIALS AND METHODS: Eighty-four patients with severe scrub typhus
      infection that also had procalcitonin levels were assessed. STATISTICAL ANALYSIS:
      Relationship between procalcitonin and mortality explored using univariate and
      multivariate analyses. RESULTS: The mean (+/-standard deviation) age was 40.0 +/-
      15.5 years. Patients were symptomatic for 8.3 +/- 4.3 days prior to presentation.
      The median admission procalcitonin level was 4.0 (interquartile range 1.8 to 8.5)
      ng/ml; 59 (70.2%) patients had levels >2 ng/ml. Invasive mechanical ventilation
      was required in 65 patients; 20 patients died. On univariate analysis, admission
      procalcitonin was associated with increased odds of death [odds ratio (OR) 1.09,
      95% confidence interval (CI) 1.03 to 1.18]. On multivariate logistic regression
      analysis including procalcitonin and APACHE-II score, the APACHE-II score was
      significantly associated with mortality (OR 1.16, 95% CI 1.06 to 1.30, P = 0.004)
      while a trend was observed with procalcitonin (OR 1.05, 95%CI 1.01 to 1.13, P =
      0.09). The area under the receiver operating characteristic (ROC) curve, AUC, for
      mortality was 0.77 for procalcitonin and 0.78 for APACHE-II. CONCLUSIONS:
      Procalcitonin is elevated in severe scrub typhus infection and may be associated
      with higher mortality.

PMID- 24082616
TI  - Death in the hospital: Breaking the bad news to the bereaved family.
AB  - Informing the family members about the sudden death of their loved one is a
      highly stressful experience for the treating doctors. Breaking the bad news to
      the bereaved family needs special skill on the part of the clinicians. An
      elaborate, step-wise modified action plan for breaking the sad news and grief
      reduction based on the literature has been presented here. The guidelines
      mentioned in the article are simply the tips to the clinicians and not to be
      considered as any form of protocols. Inclusion of this subject into the
      undergraduate medical curriculum has to be considered. By doing so, we can look
      forward to produce junior doctors who are better at coping with this awkward but
      extremely important aspect of clinical medicine. 

PMID- 24082617
TI  - Paraquat - A deadly poison: Report of a case and review.
AB  - Paraquat is a bipyridilium herbicide used widely in our country and is a highly
      toxic compound. A 16-year-old female patient was admitted to the emergency
      department of our tertiary care hospital in South India with the history of
      alleged consumption of paraquat poison. Since there is dearth of high quality
      evidence- based treatment for this poisoning, different treatment modalities have
      been tried to manage patient's condition. In this case, none of the strategies
      could work well. Most of the patients reported with paraquat intoxication are
      from agricultural background; usually such patients cannot afford the treatment
      expenses. This paper presents a fatal case of acute poisoning with paraquat who
      succumbed to acute respiratory distress syndrome (ARDS). 

PMID- 24082618
TI  - All that seems sepsis is not sepsis.
AB  - Catastrophic antiphospholipid antibody syndrome (CAPS) resembles severe sepsis in
      its acute presentation, with features of systemic inflammatory response syndrome
      (SIRS) leading to multiple organ dysfunction. Infections are the best known
      triggers of CAPS. This emphasizes the need for early diagnosis and aggressive
      treatment as the mortality is as high as 50%. We present a 42-year-old woman who
      developed SIRS postoperatively and was eventually diagnosed as CAPS. 

PMID- 24082619
TI  - Bronchial asthma with ABPA presenting as PTE.
AB  - Allergic bronchopulmonary aspergillosis (ABPA), as a complication of asthma, is
      rare in children. The persistent and poorly-controlled asthma leading to cor
      pulmonale is not uncommon in adults but rarely described in the pediatric age
      group. Here, we report a case of asthma and ABPA complicated by pulmonary thrombo
      embolism and cor pulmonale. To the best of our knowledge, such association has
      never been reported in the pediatric age group. 

PMID- 24082620
TI  - Successful resuscitation after suspected carbon dioxide embolism during
      laparoscopic ureteric reconstructive surgery.
AB  - Carbon dioxide (CO2) embolism is a rare but potentially fatal complication of
      laparoscopic surgery. We report a case of presumed CO2 embolism in a 35-year-old
      female during laparoscopic ureteric reconstructive surgery. After 2 h of
      operating time, a sudden decrease in end-tidal carbon dioxide and deterioration
      of hemodynamic status followed by cardiac arrest with pulseless electrical
      activity suggested gas embolism. Immediate cardiopulmonary resuscitation and
      inotropic support resulted in successful outcome. Thus, early recognition of the
      complication and prompt treatment can avoid catastrophy. 

PMID- 24082621
TI  - Electrocardiographic ST segment changes due to the mad honey intoxication.

PMID- 24082622
TI  - Migration of subclavian venous catheter tip: Patient positioning in ICU makes a
      difference.

PMID- 24082623
TI  - Lithium toxicity and sepsis: Time for a rethink?

PMID- 24082624
TI  - High-dose insulin therapy in a case of subarachnoid hemorrhage-related severe
      cardiodepression with ischemic-like electrocardiographic changes.

PMID- 24082625
TI  - Zinc administration modulates radiation-induced oxidative injury in lens of rat.
AB  - BACKGROUND: The aim of this study was to evaluate the antioxidant role of zinc
      (Zn) against radiation-induced cataract in the rat lens after total cranial
      irradiation with a single 5 Gray (Gy) dose of gamma irradiation. MATERIALS AND
      METHODS: Twenty-one Sprague-Dawley rats were used for the experiment. The control
      group did not receive Zn or irradiation but received 1-ml saline orally plus sham
      irradiation. The irradiation (IR) group received 5 Gy gamma irradiation to the
      total cranium as a single dose plus 0.1 ml physiological saline
      intraperitoneally. The IR plus Zn group received irradiation to total cranium
      plus 10 mg/kg/day Zn intraperitoneally. Biochemical parameters measured in rat
      lenses were carried out using spectrophotometric techniques. RESULTS: Lens total
      (enzymatic plus non-enzymatic) superoxide scavenger activity (TSSA), glutathione
      reductase (GRD), and glutathione-S-transferase (GST) activities significantly
      increased in the IR plus Zn groups when compared with the IR group. However,
      TSSA, GRD and GST activities were significantly lower in the IR group when
      compared with the control group. Lens non-enzymatic superoxide scavenger activity
      (NSSA) in the IR plus Zn group was significantly increased compared to that of
      the IR group. Lens xanthine oxidase (XO) activity in the IR group significantly
      increased compared to that of both the control and IR plus Zn groups. CONCLUSION:
      Zn has clear antioxidant properties and prevented oxidative stress by scavenging
      free radicals generated by ionizing radiation in rat lenses.

PMID- 24082626
TI  - Simultaneous determination of five marker compounds in Xuanfu Daizhe Tang by high
      performance liquid chromatography coupled with diode array detection for quality
      control.
AB  - BACKGROUND: Xuanfu Daizhe Tang (XDT) is a classical traditional Chinese medicinal
      prescription that has been widely used for treating digestive system illnesses
      for hundreds of years. MATERIALS AND METHODS: In this study, a simple and
      sensitive high-performance liquid chromatography coupled with diode array
      detection (HPLC-DAD) method was established for the simultaneous determination of
      five marker compounds in XDT including chlorogenic acid, glycyrrhizic acid,
      ginsenoside Rg1, ginsenoside Rb1 and ginsenoside Re, for quality control of this
      well-known traditional Chinese medicine (TCM). RESULTS: These compounds were
      separated in less than 130 min using a YMC C18 column with a gradient elution
      system of acetonitrile and 0.1% phosphoric acid water solution at a flow rate of
      1 ml/min. All calibration curves of standard components showed good linearity
      with R(2) >0.9991. Limit of detection and limit of quantification varied from
      0.11 to 4.3 MUg/ml and 0.20 to 11.6 MUg/ml, respectively. The relative standard
      deviations (RSDs) of the intra-day and inter-day experiments were less than 4.72
      and 5.48%, respectively. The accuracy of recovery test ranged from 95.0 to 105.0%
      with RSD values 1.28- 4.32%. CONCLUSION: The validated method is simple,
      reliable, and successfully applied to determine the contents of the selected
      compounds in XDT for quality control.

PMID- 24082627
TI  - In vivo pharmacokinetic comparisons of ferulic acid and puerarin after oral
      administration of monomer, medicinal substance aqueous extract and Nao-De-Sheng
      to rats.
AB  - BACKGROUND: Nao-De-Sheng decoction (NDS), a traditional Chinese medicine (TCM)
      prescription containing Radix puerariae lobatae, Floscarthami, Radix et Rhizoma
      Notoginseng, Rhizoma chuanxiong and Fructus crataegi, is effective in the
      treatment of cerebral arteriosclerosis, ischemic cerebral stroke and apoplexy
      linger effect. Ferulic acid and puerarin are the main absorbed effective
      ingredients of NDS. OBJECTIVE: To assess the affection of other components in
      medical material and compound recipe compatibility on the pharmacokinetics of
      ferulaic acid and puerarin, of ferulic acid from the monomer Rhizoma chuanxiong
      aqueous extract and NDS were studied. And pharmacokinetics comparisons of
      puerarin from the monomer Radix puerariae extract and NDS decoction were
      investigated simultaneously. MATERIALS AND METHODS: At respective different time
      points after oral administration of the monomer, medicinal substance aqueous
      extract and NDS at the same dose in rats, plasma concentrations of ferulic acid
      and puerarin in rats were determined by RP-HPLC, and the main pharmacokinetic
      parameters were estimated with 3P97 software. RESULTS: The plasma concentration
      time curves of ferulaic acid and puerarin were both best fitted with a two
      compartment model. AUC0-t , AUC0->infinity, T max, and C max of ferulic acid in
      the monomer and NDS decoction were increased significantly (P < 0.05) compared
      with that in Rhizoma chuanxiong aqueous extract. And statistically significant
      increase (P < 0.05) in pharmacokinetic parameters of puerarin including AUC0-t ,
      AUC0->infinity, CL, T max and C max were obtained after oral administration of
      puerarin monomer compared with Radix puerariae extract. Although the changes of
      AUC0-t , AUC0->infinity and CL had no statistically significant, C max of
      puerarin in NDS was increased remarkably (P < 0.05) compared with that in single
      puerarin. CONCLUSIONS: Some ingredients of Rhizoma chuanxiong and Radix puerariae
      may be suggested to remarkably influence plasma concentrations of ferulaic acid
      and puerarin. Some ingredients in NDS may increase dissolution and absorption of
      ferulaic acid and puerarin, delay elimination, and subsequently enhance
      bioavailability of ferulaic acid and puerarin in rats after compatibility.

PMID- 24082628
TI  - Determination of quercetin, plumbagin and total flavonoids in Drosera peltata
      Smith var. glabrata Y.Z.Ruan.
AB  - BACKGROUND: Drosera peltata Smith var. glabrata Y.Z.Ruan, a kind of wild
      carnivorous plants in the family Droseraceae, has been used for the treatment of
      rheumatism and bruises in Chinese folk. None of compounds in this herb has been
      quantified in the previous studies. OBJECTIVE: To develop a validated and
      reliable HPLC method for the simultaneous determination of two bioactive
      constituents - quercetin and plumbagin, and establish a simple UV
      spectrophotometry method for the analysis of total flavonoids content. MATERIALS
      AND METHODS: Chromatographic separation was performed by using a HPLC system
      consisting of an Agilent Eclipse XDB C18 column and a gradient elution system of
      acetonitrile and water (containing 0.1% phosphoric acid, V/V) within 20 minutes.
      Comparing with quercetin complex with Al(NO3)3, the total flavonoids were
      determined by UV spectrophotometry at 269 nm. RESULTS: Both methods were
      validated for linearity (r(2)>=0.9994 for quercetin and plumbagin in the HPLC
      method, r(2) = 0.9994 for quercetin in the UV spectrophotometry method),
      precision (The within-day and between-day variability was less than 0.738% and
      1.64% for quercetin and plumbagin in the HPLC method, and was less than 1.67% for
      quercetin in the UV spectrophotometry method.) and recovery (The recoveries of
      the HPLC method were 96.7-100.4% and 97.4-100.4% for quercetin and plumbagin,
      respectively, and the recovery of the UV spectrophotometry method was 96.7-99.6%
      for quercetin.). CONCLUSION: The proposed methods are simple and accurate, and
      could be practiced to rapidly determine quercetin, plumbagin and total flavonoids
      in the herbal drug, which provide effective approaches for quality control.

PMID- 24082629
TI  - Antipsoriatic activity and cytotoxicity of ethanolic extract of Nigella sativa
      seeds.
AB  - BACKGROUND: Nigella sativa Linn (Ranunculaceae) is popularly known as black cumin
      with a wide spectrum of pharmacological activities including anti-inflammatory,
      antibacterial, antifungal and antihelmenthic. The seeds are externally applied
      for eruptions of skin. The seeds are used traditionally for psoriasis tropicus
      with general pain and eruption of patches. OBJECTIVE: The ethanolic extract of
      Nigella sativa seeds were evaluated for antipsoriatic activity. MATERIALS AND
      METHODS: The screening of antipsoriatic activity of 95% of ethanolic extract of
      Nigella sativa seeds by using mouse tail model for psoriasis and in vitro
      antipsoriatic activity was carried out by SRB Assay using HaCaT human
      keratinocyte cell lines. RESULTS: The ethanolic extract of Nigella sativa seeds
      extract produced a significant epidermal differentiation, from its degree of
      orthokeratosis (71.36+/-2.64) when compared to the negative control (17.30+/
      4.09%). This was equivalent to the effect of the standard positive control,
      tazarotene (0.1%) gel, which showed a (90.03+/-2.00%) degree of orthokeratosis.
      The 95% ethanolic extract of Nigella sativa shown IC50 239 MUg/ml, with good
      antiproliferant activity compared to Asiaticoside as positive control which
      showed potent activity with IC50 value of 20.13 MUg/ml. CONCLUSION: The ethanolic
      extract of Nigella sativa seeds also showed increase in relative epidermal
      thickness when compared to control group by confirming its traditional use in
      psoriasis treatment.

PMID- 24082630
TI  - Quantitative determination of total and individual flavonoids in stems and leaves
      of Buddleja davidii and Buddleja albiflora.
AB  - BACKGROUND: Buddleja davidii and B. albiflora are two different original plants
      of the famous crude medicine "Diaoyangchen". MATERIALS AND METHODS: An
      ultraviolet-visible spectrophotometric method and a HPLC method were used for the
      determination of total and individual flavonoids (luteolin and apigenin) contents
      from their stems and leaves for the first time. RESULTS: From the comparative
      evaluation, remarkable differences in flavonoids contents were observed between
      different origins and different parts of the samples. And content of specific
      flavonoid did not correspond to the total flavonoids contents in Buddleja davidii
      and Buddleja albiflora. CONCLUSION: With a better accuracy and precision, the
      methods had been proved simple, rapid, and reliable for quantitative
      determination of the total flavonoids and luteolin and apigenin in the two
      phytomedicines. Furthermore, our present study will pave the way of guidelines
      for the differentiation and standardization and exploitation of individual parts
      of this herb material.

PMID- 24082631
TI  - Development of a rapid resolution liquid chromatography-diode array detector
      method for the determination of three compounds in Ziziphora clinopodioides Lam
      from different origins of Xinjiang.
AB  - CONTEXT: As a traditional Uygur medicinal plant, Z. clinopodioides Lam has
      various uses in Xinjiang. AIMS: A reversed-phase rapid resolution liquid
      chromatography (RP-RRLC) method with diode array detector (DAD) was developed for
      simultaneous determination of diosmin, linarin, and pulegone from Ziziphora
      clinopodioides Lam, a widely used in traditional Uygur medicine for treating
      heart disease, high blood pressure, and other diseases. SETTINGS AND DESIGN:
      Compounds were separated on a XDB-C18 reversed-phase analytical column (50 mm *
      4.6 mm, 1.8 MUm) with gradient elution using methanol and 1% aqueous acetic acid
      (v/v) at 0.9 mL/min. he detection wavelength was set at 270 nm. MATERIALS AND
      METHODS: Ziziphora clinopodioides Lam. were collected from ten different origins
      in Xinjiang, including the Ban fang ditch, Tuoli, the Altay mountains, Terks,
      Xiata Road, Zhaosu Highway, Guozigou, Fukang, Jimsar, Wulabo. STATISTICAL
      ANALYSIS USED: The intra-day and inter-day precisions of all three compounds were
      less than 0.89% and the average recoveries ranged from 97.4 to 104.1%. There were
      highly significant linear correlations between component concentrations and
      specific chromatographic peak areas (R2 > 0.999). RESULTS: The proposed method
      was successfully applied to determine the levels of three active components in Z.
      clinopodioides Lam. samples from different locations in Xinjiang. CONCLUSIONS:
      The proposed method is simple, consistent, accurate, and could be utilized as a
      quality control method for Z. clinopodioides Lam.

PMID- 24082632
TI  - Modulatory effects of Crataeva nurvala bark against testosterone and N-methyl-N
      nitrosourea-induced oxidative damage in prostate of male albino rats.
AB  - BACKGROUND: Antioxidant properties of Crataeva nurvala bark contains a variety of
      the bioactive phytochemical constituents in medicinal plants which include
      flavonoids, phenolic compounds, tannins, anthracene derivatives, and essential
      oils. Components from Crataeva nurvala bark have been accounted to play an
      important role in scavenging free radicals generated by mutagens and carcinogens.
      Androgens are the key factors in either the initiation or progression of prostate
      cancer by inducing oxidative stress. In the present set of investigations, the
      antioxidative potential of Crataeva nurvala bark extract against androgen
      mediated oxidative stress in male Wistar rats has been studied. MATERIALS AND
      METHODS: Oxidative damage in prostate was induced in rats by the injection of
      testosterone (100 mg/kg body weight [bw]) for 3 days followed by injection of
      chemical carcinogen N-Methyl N-Nitroso Urea (50 mg/kg bw) for 1 week. The
      oxidative damage in prostate-induced rats were treated with the ethanolic extract
      of Crataeva nurvala bark (150 mg/kg bw) and testosterone injection (2 mg/ kg bw)
      was also continued through the experimental period of 4 months. The prostate
      tissue was dissected out for biochemical analysis of lipid peroxidation and
      enzymic-antioxidants viz. catalase, superoxide dismutase, glutathione peroxidase,
      glutathione-S-transferase, and glutathione reductase; the non-enzymic
      antioxidants viz. reduced glutathione, and Vitamin C. RESULTS: The results
      revealed that testosterone administration induced the oxidative stress in rat
      prostate; however, in drug (150 mg/kg bw) supplemented groups, a significant
      protective effect of Crataeva nurvala bark against testosterone-induced oxidative
      injury was recorded. CONCLUSION: Hence, the study reveals that constituents
      present in Crataeva nurvala bark impart protection against androgen-induced
      oxidative injury in prostate.

PMID- 24082633
TI  - Anticonvulsant and anxiolytic activity of the peptide fraction isolated from the
      venom of the social wasp Polybia paulista.
AB  - BACKGROUND: Arthropod venoms have attracted interest because they represent a
      source of neuroactive compounds that can be useful tools in neuroscience and
      pharmacological investigations. OBJECTIVE: The purpose of the present work was to
      evaluate the anticonvulsant, anxiolytic, and behavioral effects of the peptide
      fraction separated from venom of the social wasp. MATERIALS AND METHODS: The low-
      molecular-weight compounds of the venom were separated by ultrafiltration and the
      bioassays were performed to test anticonvulsant and anxiolytic effects, as well
      as alterations in the spontaneous behavior of the animals. RESULTS:
      Intracerebroventricular injections of the compounds induced dose-dependent
      anticonvulsant effects and a potent anxiolytic activity. Regarding behavioral
      effects, no significant differences were observed in relation to the saline
      control group. CONCLUSION: The low-molecular-weight compounds of the venom of
      Polybia paulista include neuroactive peptides that can be used as pharmacological
      resources for anticonvulsant and anxiolytic drug research.

PMID- 24082634
TI  - Study on chemical fingerprinting of crude and processed Atractylodes macrocephala
      from different locations in Zhejiang province by reversed-phase high-performance
      liquid chromatography coupled with hierarchical cluster analysis.
AB  - BACKGROUND: In China, Atractylodes macrocephala is mainly distributed in Zhejiang
      province. It is, therefore, desirable to determine a reliable and accurate
      methodology to differentiate the samples collected from Zhejiang province.
      Although some studies on the fingerprints of Atractylodes macrocephala using HPLC
      have been published, none of them compared the processed product of Atractylodes
      macrocephala from different areas of Zhejiang province. MATERIALS AND METHODS:
      Reversed-phase high-performance liquid chromatography (RP-HPLC) coupled with
      hierarchical cluster analysis was employed in the fingerprint analysis of
      Atractylodes macrocephala from Zhejiang province, China. The LC assay was
      performed on a reversed-phase C18 column with linear gradient elution using water
      and acetonitrile. The LC data showed considerable variation of chemical
      constituents among Atractylodes macrocephala populations. RESULTS: 21 and 22
      characteristic peaks in the 14 grants of Atractylodes macrocephala and its
      processed product were determined in samples from different habitats of Zhejiang
      province, respectively. Their chromatographic patterns were generally consistent
      although their contents of chemical compositions were greatly different. The
      results of hierarchical cluster analysis showed that the samples could be divided
      into four groups; it was able to select excellent resources from the groups.
      CONCLUSION: This was the first report of hierarchical cluster analysis of crude
      and processed Atractylodes macrocephala according to their chemical fingerprints
      and could be applied to the intrinsic quality control of crude and processed
      Atractylodes macrocephala. The processing technique of Atractylodes macrocephala
      through the pilot-scale experiment was first studied and is simple and suitable
      for prepared yin pian of Atractylodes macrocephala industrial manufacture.

PMID- 24082635
TI  - Effect of the hexane extract of Piper auritum on insulin release from beta-cell
      and oxidative stress in streptozotocin-induced diabetic rat.
AB  - BACKGROUND: The large-leafed perennial plant Piper auritum known as Hoja Santa,
      is used for its leaves that because of their spicy aromatic scent and flavor have
      an important presence in Mexican cuisine, and in many regions, this plant is
      known for its therapeutic properties. MATERIALS AND METHODS: In the present
      study, we investigated the effect of hexane, chloroform and methanol extracts
      from Piper auritum on cell culture system and the effect in streptozotocin
      induced type 1 diabetic rats treated by 28 days on the physiological, metabolic
      parameters and oxidative stress. RESULTS: The hexane extract of P. auritum (HS)
      treatment significantly reduced the intake of both food, water and body weight
      loss as well as levels of blood glucose, serum cholesterol, triglycerides and
      increase HDL-cholesterol. After 4-week administration of HS antioxidant enzyme as
      SOD, CAT, GSH, GPx in pancreas were determined. These enzyme increased
      significantly compared with those of the diabetic rats control and normal
      animals. For all estimated, the results of HS treated groups leading to a
      restoration of the defense mechanism. The treatment also improves pancreatic
      TBARS-reactive substance level and serum NO and iNOS. To determine the insulin
      releasing activity, after extract treatment the serum and pancreatic sections
      were processed for examination of insulin-releasing activity using an
      immunocytochemistry kit. The results showed that administration of the hexane
      extract (200 and 400 mg/kg) exhibited a significant increase in serum and
      pancreas tissue insulin. Administration of streptozotocin decreased the insulin
      secretory activity in comparison with intact rats, but treatment with the HS
      extract increased significantly the activity of the beta cells in comparison with
      the diabetic control rats. The extract decreased serum glucose in streptozotocin
      induced diabetic rats and increased insulin release from the beta cells of the
      pancreas. In cultured RIN-5F cells, we examined whether hexane extract of P.
      auritum would protect the pancreas-derived beta-cells from oxidative stress.
      Moreover, HS could protect pancreatic beta-cells from advanced glycation end
      products-induced oxidative stress. CONCLUSION: From these results, HS is
      suggested to show anti-diabetic effect by stimulating insulin-dependent and by
      protecting pancreatic beta-cells from advanced glycation end products-induced
      oxidative stress.

PMID- 24082636
TI  - Effect and evaluation of antihyperlipidemic activity guided isolated fraction
      from total methanol extract of Salvadora oleoides (Decne.) in Triton WR-1339
      Induced hyperlipidemic rats.
AB  - BACKGROUND: Hyperlipidemia is implicated as the cause for coronary heart
      diseases. Though varieties of synthetic drugs are used in the treatment, still
      the searches are on for better medicaments especially from the plant kingdom.
      Many medicinal plants have been studied in this context but most of them are
      seasonal or have restricted availability. One such weed, available throughout the
      year is Salvadora oleoides (decne.). MATERIALS AND METHODS: Column
      chromatographic fractionation of the butanol fraction of leaves of Salvadora
      oleoides (decne.) yielded four fractions (fraction A-D). All sub-fractions were
      tested for their anti-hyperlipidemic activity. Fractions were administered at a
      dose of 65 mg/kg (oral) to the Triton WR-1339 induced hyperlipidemic rats.
      RESULTS: Sub-fraction D showed maximum significant reduction (P<0.05) among four
      sub-fractions in comparison with standard drug fenofibrate. CONCLUSION: Further
      studies on the isolated fractions and constituents are needed to isolate compound
      responsible for activity and elucidate the mechanism by which Salvadora oleoides
      (decne.) exerts protective effects against hyperlipidemia.

PMID- 24082637
TI  - Comparison of the antiproliferative activity of crude ethanol extracts of nine
      salvia species grown in Jordan against breast cancer cell line models.
AB  - BACKGROUND: The antiproliferative activity of Salvia species grown in Jordan has
      not been fully evaluated yet. The aim of this work was to study the
      antiproliferative activity of crude ethanol extracts from nine Salvia species
      grown in Jordan against a panel of breast cancer cell lines. MATERIAL AND
      METHODS: Cytotoxic activity was evaluated in human tumor models of breast cancer;
      MCF-7, T47D, ZR-75-1, and BT 474 by the sulforhodamine B assay. In addition, the
      extracts were evaluated using a non-transformed cell line (Vero) and normal
      fibroblast cells in order to demonstrate their selectivity and safety. RESULTS:
      From the nice ethanol extracts under investigation, those of S. dominica and S.
      fruticosa showed an inhibitory concentration of 50% of cells (IC50) in
      concentrations less than 30MUg/mL against the four cell lines under
      investigation. S. syriaca and S. hormium showed an IC50 below 30MUg/ml for two
      out of the four cell lines. S. fruticosa, S. hormium and S. syriaca showed
      selectivity in their antiproliferative activity against estrogen receptor
      positive cell lines with minimal toxicity against normal human periodontal
      fibroblasts. Phytochemical screening using thin layer chromatography indicated
      the presence of terpenoids, flavonoids and coumarins in all examined extracts.
      CONCLUSION: Three of the plant extracts under investigation exhibited
      antiproliferative activity against breast cancer cells and were shown to be safe
      and selective. These could be considered as a potential source for novel
      anticancer therapy.

PMID- 24082638
TI  - Life span effects of Hypericum perforatum extracts on Caenorhabditis elegans
      under heat stress.
AB  - BACKGROUND: The beneficial effects of antioxidants in plants are mainly
      extrapolated from in vitro studies or short-term dietary supplementation studies.
      Due to cost and duration, relatively little is known about whether dietary
      antioxidants are beneficial in whole animals' life span or not. MATERIALS AND
      METHODS: To address this question, under heat stress (35 degrees C), Hypericum
      perforatum was extracted with petroleum ether and the nematodes Caenorhabditis
      elegans exposed to three different extract concentrations (1mg/mL, 0.1mg/mL,
      0.01mg/mL) of H. perforatum. RESULTS: We report that Hypericum perforatum
      extracts did not increase life span and slow aging related increase in C.
      elegans. Moreover, one fraction (1mg/mL) increased declines of C. elegans life
      span and thermotolerance. CONCLUSION: Given this mounting evidence for life span
      role of H. perforatum in the presence of heat stress in vivo, the question
      whether H. perforatum acts as a prooxidant or an antioxidant in vivo under heat
      stress arises.

PMID- 24082639
TI  - Occupational health nursing-growing influence at workplace in India.

PMID- 24082640
TI  - Is medicine turning into unhappy profession?
AB  - BACKGROUND: Stress is one of the most common problems; one manifestation of
      stress is burnout. Burnout and other stress-related illnesses among medical
      professionals are receiving increased attention and have been described in many
      branches of medical practice including dentists, nurses, etc., The purpose of
      this study was to measure the prevalence of stress and burnout in medical
      professionals in Rajasthan. MATERIALS AND METHODS: The Maslach Burnout Inventory
      Human Service Survey (MBI-HSS) and a demographic questionnaire of our own design
      were sent to 1,735 medical professional of various branches and different
      location throughout the state of Rajasthan. In response to that, 627 (36%)
      surveys were returned, of which 576 (92%) were found complete for analysis so
      later group constitute as sample for analysis. RESULT: 29.16% of medical
      professional showed high level of emotional exhaustion (EE), 20% showed high
      level of depersonalization (DP), and 17.9% showed low personal accomplishment
      (PA). Young professionals showed more sensitivity towards burnout (r = -0.122, P
      < 0.003). Females were more prone to burnout (40%) as compared to males (27%).
      CONCLUSION: Burnout is an important problem in medical professionals in
      Rajasthan. Difference in approach to work and perceived environment at workplace,
      unrewarding career, unsupported behavior of peer group, balance between work and
      family needs appear to be important factors in burnout.

PMID- 24082641
TI  - Adverse health effects of occupational exposure to radiofrequency radiation in
      airport surveillance radar operators.
AB  - INTRODUCTION: Radar workers are exposed to pulsed high frequency electromagnetic
      fields. In this study, health effects of these radiations in personnel who
      routinely work with radar systems are investigated. MATERIALS AND METHODS: The 28
      item General Health Questionnaire was used as a self-administered tool for
      assessment of general mental health and mental distress. One hundred workers
      occupationally exposed to radar radiations (14-18 GHz) participated in the study.
      Visual reaction time was recorded with a simple blind computer-assisted-visual
      reaction time test. To assess the short-term memory, Wechsler Memory Scale-III
      test was performed. RESULTS: Twenty to 39% of the radar workers reported
      different problems such as needing a good tonic, feeling run down and out of
      sorts, headache, tightness or pressure in the head, insomnia, getting edgy and
      bad-tempered. Furthermore, 47% of the radar workers reported feeling under
      strain. In response to this question that if they have been able to enjoy their
      normal day-to-day activities, 31% responded less than usual. It was also shown
      that work experience had significant relationships with reaction time and short
      term memory indices i.e., forward digit span, reverse digit span, word
      recognition and paired words. CONCLUSION: To the best of our knowledge, this is
      the first study to show that occupational exposure to radar microwave radiation
      leads to changes in somatic symptoms, anxiety and insomnia, social dysfunction,
      and severe depression. Altogether these results indicate that occupational
      exposure to radar microwave radiations may be linked to some adverse health
      effects.

PMID- 24082642
TI  - A pilot study on the prevalence of Acute Mountain Sickness at the Sikh pilgrimage
      of Hemkund Sahib in the Indian Himalayas.
AB  - BACKGROUND: Hemkund Sahib is a popular pilgrimage located at 4,330 m in the
      Garhwal range of the Indian Himalayas. Many travelers to the region have observed
      pilgrims exhibiting Acute Mountain Sickness (AMS)-like symptoms. However, no
      systematic study on its prevalence at Hemkund has been conducted. MATERIALS AND
      METHODS: We surveyed 25 adults. AMS rates were determined using a standard Lake
      Louise Score (LLS). Responses to questions related to awareness of AMS, the
      perceived difficulty of the trek, and physiological data including arterial
      oxygen saturation (SpO2) and pulse rate, amongst others, were collected. RESULTS:
      Overall prevalence of AMS was 28% (mild AMS 20%, severe AMS 8%). Borg Rating of
      Perceived Exertion (RPE) was 3.9/10. Water consumption for the 4-5 hour trek to
      Hemkund was only 0.9 L and 20% of pilgrims consumed no water at all. Nine
      pilgrims claimed to be aware of AMS although only one had taken prophylactic
      medication. SpO2 was 82.2 +/- 1.2% and pulse rate was 106.5 +/- 2.9 bpm (mean +/-
      SEM). There were no differences in non-LLS-related parameters when pilgrims were
      subdivided by presence or absence of AMS. CONCLUSION: This pilot study has, for
      the first time, documented the prevalence of AMS amongst pilgrims to Hemkund
      Sahib in the Indian Himalayas.

PMID- 24082643
TI  - Knowledge, attitudes, and poultry-handling practices of poultry workers in
      relation to avian influenza in India.
AB  - Avian influenza (AI) is a viral disease of domestic and wild birds. The recent
      pandemics caused by highly pathogenic AIA (H5N1) in domestic poultry is currently
      rated phase 3 by the World Health Organization on the pandemicalert scale.
      MATERIALS AND METHODS: A pretested and semistructured survey instrument was
      administered to both live bird market and poultry farm workers in two most
      populous cities in Karnataka in South India to collect data on demographics,
      knowledge, attitude, and practices among them. RESULTS: The mean age was similar
      among both population groups (31.5 years). There was a higher level of
      biosecurity practices adopted in poultry farms compared with those adopted in
      live bird market. Knowledge regarding AI was acceptable but poorly correlated
      with actual biosecurity practices. DISCUSSION: Live bird market and poultry farm
      workers have been identified as the weakest link in the prevention and control of
      the spread of AI in the two most populous cities studied in Karnataka.
      CONCLUSION: Risk reduction models of behavior change targeting these groups are
      important toward the control and prevention of AI spread.

PMID- 24082644
TI  - Cutaneous mercury granuloma.
AB  - Cutaneous mercury granuloma is rarely encountered. Clinically it may pose
      difficulty in diagnosis. Here, we report a 23-year-old male presented with
      erythematous, nodular lesions over the forearm and anterior aspect of chest wall.
      Metallic mercury in tissue sections appear as dark black, opaque, spherical
      globules of varying size and number. They are surrounded by granulomatous foreign
      body reaction. It is composed of foreign body giant cells and mixed inflammatory
      infiltrate composed of histiocytes, lymphocytes, plasma cells, and few
      eosinophils. 

PMID- 24082645
TI  - Silicosis in Coimbatore district of Tamil Nadu: A passive surveillance study.
AB  - INTRODUCTION: SILICOSIS IN COIMBATORE DISTRICT OF TAMIL NADU: A passive
      surveillance study. AIM: This study was done to describe the level of preventive
      measures and level of awareness among the patients diagnosed with silicosis
      during a one-year period. SETTINGS AND DESIGN: Coimbatore Medical College
      Hospital. MATERIALS AND METHODS: This is a passive surveillance study based on
      patients diagnosed with silicosis in our outpatient facility for a one-year
      period between January 1, 2012 and December 31, 2012. RESULTS: Seventeen cases of
      silicosis were diagnosed based on history of exposure to silica and radiological
      features. The mean age was 55 years with 16 males and one female. The average
      duration of exposure was 22 years. A protective mask was used by 29% of the
      patients and one patient had awareness about the risks of exposure to silica.
      Active tuberculosis was found in 12% and old tuberculosis in 47% of patients; 59%
      of the patients were smokers. Spirometry showed a restrictive pattern in 59% of
      the patients. Radiologically nodular opacities with upper-zone predominance was
      found in majority of the cases. CONCLUSION: Most patients are exposed to silica
      in unorganized industries. Majority of the patients lack awareness about the
      disease and there is a low implementation of preventive and control measures. As
      this study was a passive surveillance, it represents only the tip of iceberg and
      an active field-level surveillance could reveal the true prevalence of this
      disease.

PMID- 24082646
TI  - Occupational history: A neglected component of history taking.

PMID- 24082647
TI  - From the Editor's desk.

PMID- 24082648
TI  - Preimplantation and postimplantation therapy for the treatment of reproductive
      failure.
AB  - Treatment of patients with recurrent pregnancy losses and recurrent implantation
      failure can be instituted only when the underlying etiology is determined. Embryo
      secreted preimplantation factor (PIF) is essential for implantation and adequate
      trophoblastic invasion. Deficiency of PIF affects the outcome of the pregnancy
      leading to recurrent pregnancy losses. Synthetic PIF modulates the outcome of the
      pregnancy decreasing the incidence of recurrent implantation failure and
      recurrent pregnancy losses. In this article a thorough search is done regarding
      the data published for diagnoses of reproductive failure and its treatment. The
      effect of immunoglobulin (Ig), intralipid, heparin, aspirin, progesterone,
      estrogen, and granulocyte colony stimulating factor (G-CSF) is taken into
      consideration. Heparin, aspirin, and progesterone have successfully shown to
      decrease the incidence of recurrent pregnancy loses; whereas G-CSF, intralipids,
      estrogen, and Igs have shown success in the treatment of the recurrent
      implantation failure and recurrent pregnancy failure. The pregnancies treated
      with Igs and intralipids showed equal outcome when evaluated and compared. The
      place of intralipid in reducing natural killer (NK) cells has been discussed. 

PMID- 24082649
TI  - Current evidence supporting "letrozole" for ovulation induction.
AB  - Aromatase inhibitor "letrozole" was first introduced as a potential ovulation
      induction (OI) drug almost a decade back. Large number of studies has been
      published using letrozole for OI: In polycystic ovary syndrome (PCOS) women,
      clomiphene citrate (CC) resistant women, for intrauterine insemination and also
      in various protocols of mild stimulation for in vitro
      fertilization/intracytoplasmic sperm injection (IVF/ICSI). Letrozole appears to
      be a good option, with its oral route of administration, cost, shorter half-life
      and negligible side effects. However, the verdict on efficacy and safety of
      letrozole is still uncertain. This review explores the current scientific data
      supporting letrozole for OI. 

PMID- 24082650
TI  - Follicular-fluid anti-Mullerian hormone (FF AMH) is a plausible biochemical
      indicator of functional viability of oocyte in conventional in vitro
      fertilization (IVF) cycles.
AB  - CONTEXT: Oocyte quality may be a governing factor in influencing in vitro
      fertilization (IVF) outcomes. However, morphological evaluation of oocyte quality
      is difficult in conventional IVF cycles. Follicular-fluid (FF), the site for
      oocyte growth and development, has not yet been sufficiently explored to obtain a
      marker indicative of oocyte quality. Anti-Mullerian hormone (AMH) is produced by
      granulosa cells of preantral and early-antral follicles and is released in FF.
      AIM: To investigate AMH as a biochemical indicator of functional
      viability/quality of oocyte produced in the FF micro-environmental milieu.
      SETTINGS AND DESIGN: Prospective study involving 132 cycles of conventional IVF
      embryo transfer (ET) in infertile women. SUBJECTS AND METHODS: AMH concentration
      was estimated in pooled FF on day of oocyte pickup. Cycles were sorted into low
      and high groups according to median (50 (th) centile) values of measurement. Main
      outcome measure was oocyte viability, which included morphological assessment of
      oocyte quality, fertilization rate, clinical pregnancy, and implantation rates.
      STATISTICAL ANALYSIS: Graph-pad Prism 5 statistical package. RESULTS: Low FF AMH
      group shows significantly higher percentage of top-quality oocytes (65.08 +/-
      24.88 vs. 50.18 +/- 25.01%, P =0.0126), fertilization (83.65 +/- 18.38 vs. 75.78
      +/- 21.02%, P =0.0171), clinical pregnancy (57.57 vs. 16.67%, P >0.0001), and
      embryo implantation rates (29.79 vs. 7.69%, P >0.0001) compared to high FF AMH
      group. FF AMH shares an inverse correlation with FF E2 (Pearson r = -0.43, r(2) =
      0.18) and clinical pregnancy (Pearson r = -0.46, r(2) = 0.21). Threshold value of
      FF AMH for pregnancy is >1.750 ng/mg protein. CONCLUSION: FF AMH is a plausible
      biochemical indicator of functional viability of oocyte in conventional IVF
      cycles.

PMID- 24082651
TI  - Unilateral and bilateral cryptorchidism and its effect on the testicular
      morphology, histology, accessory sex organs, and sperm count in laboratory mice.
AB  - BACKGROUND: Experimental unilateral cryptorchidism (ULC) and bilateral
      cryptorchidism (BLC) are excellent methods to study undescended testis in
      relation to spermatogenesis against a temperature gradient. OBJECTIVES: In case
      of ULC, it is possible to compare the testicular functions between normal
      condition and cryptorchidism in the same animal, whereas BLC shows the necessity
      of testicular androgens for proper maintenance of reproductive structures and
      functions. MATERIALS AND METHODS: In the present study, experimental ULC and BLC
      was done on same-aged adult mature male mice and kept for 15 days and 30 days,
      respectively, to observe the changes due to the induced cryptorchidism on the
      different reproductive organs, viz., the testis and accessory sex organs along
      with epididymal sperm count. Reproductive tissues were collected from individual
      animals and histopathological studies of testis were done to investigate
      different cytological changes. RESULTS: The size of the testes and accessory sex
      organs were found to be significantly reduced in BLC mice, whereas only
      testicular weight reduction was observed in ULC mice. Histopathological studies
      showed degenerative changes throughout the seminiferous tubules. CONCLUSION:
      Thus, the present investigation showed compensatory androgen production in ULC
      mice, whereas absence of androgen mediated reproductive functions in BLC animals.

PMID- 24082652
TI  - Micro-dissection testicular sperm extraction as an alternative for sperm
      acquisition in the most difficult cases of Azoospermia: Technique and preliminary
      results in India.
AB  - CONTEXT: Non-obstructive azoospermia (NOA) is an unfavorable prognostic condition
      for male infertility since spermatogenesis is disrupted. Sperm retrieval (SR)
      coupled with intracytoplasmic sperm injection (ICSI) is the only option for men
      with NOA who seek fertility. Among the SR techniques, microdissection testicular
      sperm extraction (micro-TESE) has been applied with encouraging results. AIMS: We
      describe how we implemented the micro-TESE procedure and present initial micro
      TESE experience in a group of men with NOA and poor prognosis for SR. SETTINGS
      AND DESIGN: Case series of men with NOA treated in a tertiary healthcare center.
      MATERIALS AND METHODS: An Assisted Reproductive Technology (ART) facility was
      setup to perform SR using microsurgery. Fourteen men with NOA and previous failed
      retrievals or unfavorable histologic results underwent micro-TESE while their
      female partners received ovarian stimulation for oocyte pickup (OCP). Micro-TESE
      was performed the day prior to OCP and testicular sperm were used for sperm
      injections. We assessed retrieval rates and ICSI outcomes. STATISTICAL ANALYSIS:
      Outcomes of SR and ICSI were analyzed descriptively. Mann-Whitney and Fisher
      exact test were used to compare characteristics of men with successful and failed
      SR. RESULTS: The success of micro-TESE was 50.0% with no major complications. A
      clear microscopic distinction between enlarged and collapsed seminiferous tubules
      was seen in 35.7% of the cases, and sperm were retrieved in all but one of these
      cases. Patients with successful and failed retrieval did not differ with respect
      to baseline characteristics, use of medical therapy, presence of varicocele, and
      testicular histology. Sperm injections resulted in normal fertilization and
      embryo cleavage of 64% and 75%, respectively. A total of five transfers with an
      average of 1.5 embryos resulted in a cumulative clinical pregnancy rate per ICSI
      cycle of 28.6%, with an implantation rate of 33.3%. CONCLUSIONS: We were
      successful in integrating the micro-TESE procedures to the in vitro fertilization
      (IVF) laboratory. Our initial experience with micro-TESE applied to the most
      difficult cases of azoospermia is reassuring.

PMID- 24082653
TI  - Male reproductive health under threat: Short term exposure to radiofrequency
      radiations emitted by common mobile jammers.
AB  - BACKGROUND: Modern life prompted man to increasingly generate, transmit and use
      electricity that leads to exposure to different levels of electromagnetic fields
      (EMFs). Substantial evidence indicates that exposure to common sources of EMF
      such as mobile phones, laptops or wireless internet-connected laptops decreases
      human semen quality. In some countries, mobile jammers are occasionally used in
      offices, shrines, conference rooms and cinemas to block the signal. AIMS: To the
      best of our knowledge, this is the first study to investigate the effect of short
      term exposure of human sperm samples to radiofrequency (RF) radiations emitted by
      common mobile jammers. SUBJECTS AND METHODS: Fresh semen samples were collected
      by masturbation from 30 healthy donors who had referred to Infertility Treatment
      Center at the Mother and Child Hospital with their wives. Female problem was
      diagnosed as the reason for infertility in these couples. STATISTICAL ANALYSIS: T
      test and analysis of variance were used to show statistical significance.
      RESULTS: The motility of sperm samples exposed to jammer RF radiation for 2 or 4
      h were significantly lower than those of sham-exposed samples. These findings
      lead us to the conclusion that mobile jammers may significantly decrease sperm
      motility and the couples' chances of conception. CONCLUSION: Based on these
      results, it can be suggested that in countries that have not banned mobile jammer
      use, legislations should be urgently passed to restrict the use of these signal
      blocking devices in public or private places.

PMID- 24082654
TI  - Cytogenetic evaluation of patients with clinical spectrum of Turner syndrome.
AB  - AIM: The objective of this study was to correlate the genotype, of female
      patients, withshort stature and primary amenorrhea. MATERIALS AND METHODS: One
      hundred and forty-six subjects were recruited during 2005-2012. Microscopic and
      automated karyotyping analyses were done by using chromosomes isolated from the
      lymphocytes using Giemsa banding (GTG) to identify chromosome abnormalities.
      RESULTS: A total of 146 clinically suspected Turner syndrome (TS) subjects were
      recruited for the study, of which, 61 patients were identified to have chromosome
      abnormalities. The chromosomal abnormalities detected were as follows: Monosomy X
      (n = 19, 13.01%), triple X syndrome (n = 4, 2.7%), mosaic TS (n = 12, 8.21%), XY
      gonadal dysgenesis (n = 13, 8.9%), and structural abnormalities including X
      chromosome (n = 15, 10.27%) and one patient each with autosomal changes involving
      9qh inversion and translocation of chromosomes 12 and 14. CONCLUSION: Karyotype
      abnormalities accounting for 46% in this study emphasize the need for karyotype
      testing in cases of short stature with primary amenorrhea.

PMID- 24082655
TI  - Non-invasive metabolomic analysis using a commercial NIR instrument for embryo
      selection.
AB  - CONTEXT: Metabolomics was introduced in human in vitro fertilization (IVF) for
      noninvasive identification of viable embryos with the highest developmental
      competence. AIMS: To determine whether embryo selection using a commercial
      version of metabolomic analysis leads to increased implantation rates (IRs) with
      fetal cardiac activity (FCA) compared with morphology evaluation alone. SETTING
      AND DESIGN: Randomized controlled trial from April to December 2010 at a private
      IVF unit. The study was terminated prematurely due to the market withdrawal of
      the instrument. MATERIALS AND METHODS: IVF patients >=18 and <=43 years with >=4
      * 2PN were randomly allocated to metabolomic analysis combined with embryo
      morphology (ViaMetrics-E; metabolomics + morphology group) or embryo morphology
      alone (morphology group). Cycles with frozen embryos, oocyte donations, or
      testicular biopsy were excluded. STATISTICAL ANALYSIS: Categorical and continuous
      data were analyzed for statistical significance using 2-tailed Fisher's exact
      test and t-test, respectively. Statistical significance was accepted when P >
      0.05. RESULTS: A total of 125 patients were included in the study; 39 patients
      were allocated to metabolomics + morphology group and 86 patients to morphology
      group. Patients were stratified according to the day of embryo transfer (Days 2,
      3, or 5). IRs with FCA were similar for Days 2 and 3 transfers in both groups.
      For Day 5 transfers, IRs with FCA were significantly higher in the metabolomics +
      morphology group (46.8% vs. 28.9%; P = 0.041; 95% confidence intervalp [CI]: 1.09
      34.18). Pregnancy and live births rates were similar for Days 2, 3, and 5 in both
      groups. The study was terminated early following the voluntary market withdrawal
      of ViaMetrics-E in December 2010. CONCLUSIONS: Metabolomic analysis using the
      commercial near-infrared (NIR) instrument does not appear to have a beneficial
      effect on pregnancy and live births, with improvement in IR with FCA for Day 5
      transfers. However, no solid conclusions can be reached due to the lack of
      adequate study power.ClinicalTrials.gov Identifier: NCT01490515.

PMID- 24082656
TI  - Follicular fluid insulin like growth factor-1 (FF IGF-1) is a biochemical marker
      of embryo quality and implantation rates in in vitro fertilization cycles.
AB  - CONTEXT: Insulin-like growth factor-1 (IGF-1) has been reported to play a role in
      human follicular and embryonic development. However, earlier studies carried out
      mostly in animal models or in culture mediums supplemented with IGF-1 have been
      unable to directly link IGF-1 with embryo quality. Results correlating IGF-1 with
      pregnancy outcome have also been ambiguous so far. AIM: The aim of this study is
      to find if in situ follicular-fluid level of IGF-1 is predictive of embryo
      quality and implantation rates in in vitro fertilization (IVF) cycles. SETTINGS
      AND DESIGN: Prospective study involving 120 cycles of conventional IVF-embryo
      transfer in infertile women. SUBJECTS AND METHODS: IGF-1 concentrations were
      estimated in pooled follicular-fluid on the day of oocyte-pickup. Embryo quality
      was assessed daily at different developmental stages. Cycles were sorted into low
      and high follicular fluid insulin-like growth factor-1 (FF IGF-1) groups
      according to the median value of measurement. Embryo quality, clinical pregnancy
      and implantation rate were the main outcome measures. STATISTICAL ANALYSIS: Graph
      pad Prism 5 statistical package. RESULTS: FF IGF-1 correlates with embryo quality
      (Pearson r = 0.3894, r (2) = 0.1516, P > 0.0001) and clinical pregnancy (Pearson
      r = 0.5972, r (2) = 0.36, P > 0.0001). High FF IGF-1 group shows significantly
      higher rates of fertilization, cleavage, blastocyst formation and top grade
      embryos compared with low FF IGF-1 group. Clinical pregnancy rates (38.33 vs.
      20%, P = 0.0272) and embryo implantation rates (21.6 vs. 10.32%, P = 0.0152) are
      also significantly higher in the high versus low FF IGF-1 group. Threshold value
      of FF IGF-1 for clinical pregnancy is <58.50 ng/mg protein (receiver operating
      characteristics AUC : 0.85 +/- 0.03, 95% CI: 0.78-0.91). CONCLUSION: FF IGF-1 is
      a plausible biochemical marker of embryo quality and implantation rate and
      correlates with clinical pregnancy rates in conventional IVF cycles.

PMID- 24082657
TI  - Correlation between serum zinc levels and successful immunotherapy in recurrent
      spontaneous abortion patients.
AB  - BACKGROUND: Immunotherapy with paternal lymphocytes plays an important role in
      preventing recurrent spontaneous abortion (RSA) and is an effective treatment for
      it. This kind of treatment is performed as an immunotherapy method in several
      centers in the world. It attributes to the production of anti-paternal cytotoxic
      antibodies (APCAs) in women with RSA. Production of APCA after lymphocyte
      immunotherapy (LIT) in RSA patients gives them a better chance for successful
      pregnancy. Regarding the important effect of trace elements on the function of
      the immune system, we tried to investigate the correlation between serum zinc
      level and the success of LIT in RSA. MATERIALS AND METHODS: Serum zinc
      concentration was determined in two groups of RSA patients using atomic
      absorption spectrophotometer systems. Group (a) that responded to the paternal
      lymphocytes and their cross-match test was positive, and group (b) that had no
      response to the paternal lymphocytes immunizations and their cross-match test was
      negative. RESULTS: Serum zinc levels in group (a) patients were 74.98 +/- 11.88
      MUg/dl, which was significantly higher than those in group (b) with the zinc
      concentration of 64.22 +/- 9.22 MUg/dl. CONCLUSIONS: Zinc deficiency may be one
      of the substantial causes of negative results for LIT in RSA patients. Therefore,
      compensation of zinc defect before LIT can be a promising approach to improve the
      immune response in patients.

PMID- 24082658
TI  - Efficacy of two sperm preparation techniques in reducing non-specific bacterial
      species from human semen.
AB  - CONTEXT: Artificial reproductive techniques using seminal preparations with
      bacteria may cause pelvic inflammatory disease and its sequalae. AIMS: To assess
      efficacy of two sperm preparation techniques to clear bacteria and the effect of
      bacteriospermia on sperm recovery rates. SETTINGS AND DESIGN: A descriptive cross
      sectional study was carried out among males of subfertile couples. SUBJECTS AND
      METHODS: Semen samples were randomly allocated into swim-up method (group S, n =
      68) and density gradient method (group D, n = 50) for sperm preparation. Seminal
      fluid analysis and bacterial cultures were performed in each sample before and
      after sperm preparation. STATISTICAL ANALYSIS: McNemar's chi-squared test and
      independent samples t-test in SPSS version 16.0 were used. RESULTS: Organisms
      were found in 86 (72.88%) out of 118 samples, before sperm preparation;
      Streptococcus species (n = 40, 46.51% of which 14 were Group D Streptococcus
      species), Coagulase negative Staphylococcus species (n = 17, 19.76%),
      Staphylococcus aureus (n = 13, 15.11%), Coliform species (n = 11, 12.79% of which
      09 were Escherichia coli) and Corynebacterium species (n = 5, 5.81%). There was a
      statistically significant reduction of culture positive samples in raw vs.
      processed samples; in group S, 49 (72.05%) vs. 16 (23.52%) and in group D, 37
      (74%) vs. 18 (36%). In group S and D, mean (SD) recovery rates of culture
      positive vs. culture negative samples were 39.44% (SD-14.02) vs. 44.22% (SD
      22.38), P = 0.39 and 52.50% (SD-37.16) vs. 49.58% (SD-40.32), P = 0.82
      respectively. CONCLUSIONS: Both sperm preparation methods significantly reduced
      bacteria in semen, but total clearance was not achieved. Sperm recovery rate was
      not affected by bacteriospermia.

PMID- 24082659
TI  - Case report on spontaneous ovarian hyperstimulation syndrome following natural
      conception associated with primary hypothyroidism.
AB  - Spontaneous OHSS is a rare event in pregnancy following natural conception and
      only a few cases have been reported in the literature so far. This report is a
      case of spontaneously conceived pregnancy with Spontaneous OHSS and Primary
      hypothyroidism. 

PMID- 24082660
TI  - Magnetic resonance imaging in obstructive Mullerian anomalies.
AB  - Herlyn-Werner-Wunderlich (HWW) syndrome is a very rare congenital anomaly of the
      urogenital tract involving Mullerian ducts and Wolffian structures. It is
      characterized by the triad of didelphys uterus, obstructed hemivagina, and
      ipsilateral renal agenesis. Magnetic resonance imaging (MRI) is a sensitive, non
      invasive diagnostic modality for demonstrating anatomic variation and associated
      complications. 

PMID- 24082661
TI  - Progesterone supplementation - Beware of changes in the oral cavity.

PMID- 24082662
TI  - A vision for optometry in Oman.

PMID- 24082664
TI  - Ocular chemical injuries and their management.
AB  - Chemical burns represent potentially blinding ocular injuries and constitute a
      true ocular emergency requiring immediate assessment and initiation of treatment.
      The majority of victims are young and exposure occurs at home, work place and in
      association with criminal assaults. Alkali injuries occur more frequently than
      acid injuries. Chemical injuries of the eye produce extensive damage to the
      ocular surface epithelium, cornea, anterior segment and limbal stem cells
      resulting in permanent unilateral or bilateral visual impairment. Emergency
      management if appropriate may be single most important factor in determining
      visual outcome. This article reviews the emergency management and newer
      techniques to improve the prognosis of patients with chemical injuries. 

PMID- 24082663
TI  - Optic nerve hypoplasia.
AB  - Optic nerve hypoplasia (ONH) is a congenital anomaly of the optic disc that might
      result in moderate to severe vision loss in children. With a vast number of cases
      now being reported, the rarity of ONH is obviously now refuted. The major aspects
      of ophthalmic evaluation of an infant with possible ONH are visual assessment,
      fundus examination, and visual electrophysiology. Characteristically, the disc is
      small, there is a peripapillary double-ring sign, vascular tortuosity, and
      thinning of the nerve fiber layer. A patient with ONH should be assessed for
      presence of neurologic, radiologic, and endocrine associations. There may be
      maternal associations like premature births, fetal alcohol syndrome, maternal
      diabetes. Systemic associations in the child include endocrine abnormalities,
      developmental delay, cerebral palsy, and seizures. Besides the hypoplastic optic
      nerve and chiasm, neuroimaging shows abnormalities in ventricles or white- or
      gray-matter development, septo-optic dysplasia, hydrocephalus, and corpus
      callosum abnormalities. There is a greater incidence of clinical neurologic
      abnormalities in patients with bilateral ONH (65%) than patients with unilateral
      ONH. We present a review on the available literature on the same to urge caution
      in our clinical practice when dealing with patients with ONH. Fundus photography,
      ocular coherence tomography, visual field testing, color vision evaluation,
      neuroimaging, endocrinology consultation with or without genetic testing are
      helpful in the diagnosis and management of ONH. (Method of search: MEDLINE,
      PUBMED). 

PMID- 24082665
TI  - The eye and visual system in pregnancy, what to expect? An in-depth review.
AB  - Pregnancy represents a real challenge to all body systems. Physiological changes
      can involve any of the body organs including the eye and visual system. The
      ocular effect of pregnancy involves a wide spectrum of physiologic and pathologic
      changes. The latter might be presenting for the first time during pregnancy such
      as corneal melting and corneal ectasia, or an already existing ocular pathologies
      that are modified by pregnancy such as diabetic retinopathy and glaucoma. In
      addition, pregnancy can affect vision through systemic disease that are either
      specific to the pregnant state itself such as the pre-eclampsia/eclampsia and
      Sheehan's syndrome, or systemic diseases that occur more frequently in relation
      to pregnancy such as Graves' disease, idiopathic intracranial hypertension, anti
      phospholipid syndrome, and disseminated intravascular coagulation. 

PMID- 24082666
TI  - Selective laser trabeculoplasty: Does energy dosage predict response?
AB  - BACKGROUND: Selective laser trabeculoplasty (SLT) is a widely used treatment for
      open angle glaucoma, producing sustained reductions of intraocular pressure
      (IOP). The aim of this study was to evaluate the long-term relationship between
      SLT energy dosage and IOP reduction. MATERIALS AND METHODS: A retrospective
      review was performed for patients receiving primary SLT therapy, with inclusion
      of subjects treated with 360 degrees  of SLT. Energy settings were collected upon
      treatment and IOP was collected at baseline up to 36 months. Pearson's
      correlation coefficient was used to determine whether there was a significant
      correlation between SLT energy and IOP reduction at all time points. Kaplan-Meier
      analysis with log-rank test was performed to determine the differences in IOP
      reduction >=20% from baseline among those treated with low (<85 mJ), medium (85
      105 mJ), and high (>105 mJ) energy SLT. RESULTS: A total of 104 eyes (75
      patients) were included. The mean total SLT energy was 93.73 mJ (standard
      deviation (SD) = 21.83 mJ, range: 34.4-122 mJ). A significant positive
      correlation (P <= 0.05) between the amount of energy delivered and IOP reduction
      was found at all time points. Log-rank test showed a significant difference in
      IOP reduction >=20% from baseline between the three energy groups, with low
      energy patients experiencing failure at an earlier time (P = 0.05). CONCLUSIONS:
      Within the range of total energy examined, there is a positive correlation
      between total energy used and amount of pressure reduction achieved at up to 3
      years of follow-up. This may be useful in determining the optimal energy dosage
      for maximum effect for patients receiving SLT.

PMID- 24082667
TI  - Correlation of visual functions with macular thickness in primary open angle
      glaucoma.
AB  - AIM: The aim of this study was to establish a correlation between macular
      thickness on optical coherence tomography (OCT) and 2 visual functions (visual
      acuity and contrast sensitivity [CS]) in established cases of primary open angle
      glaucoma (POAG). MATERIALS AND METHODS: A total of 50 consecutive patients of
      established POAG between 40 years and 70 years of age attending the glaucoma
      clinic of a tertiary care eye center in North India were enrolled for this cross
      sectional study. Best corrected visual acuity (BCVA), CS and macular thickness by
      spectral-domain-OCT (Cirrus HD-OCT, CarlZeiss, Germany) were evaluated.
      STATISTICAL ANALYSIS: The groups were compared together by one factor analysis of
      variance and the significance of mean difference between the groups was done by
      Newman-Keuls test. RESULTS: Newman-Keuls test revealed a direct relationship of
      macular thickness to BCVA and CS (P < 0.05). CONCLUSION: BCVA and CS are directly
      related to the macular thickness on OCT.

PMID- 24082668
TI  - Transcanalicular endoscope combined laser-assisted dacryocystorhinostomy.
AB  - AIMS: In this study, we have tried to assess the success rate and difficulties
      that we came across while performing the transcanalicular endoscope combined
      laser-assisted dacryocystorhinostomy (T-ECLAD). MATERIALS AND METHODS: A
      prospective study of 60 patients suffering from nasolacrimal duct obstruction
      confirmed by preoperative syringing was carried out at the Regional Institute of
      Ophthalmology. T-ECLAD is a new minimally invasive dacryocystorhinostomy
      procedure, which is performed by diode laser (980 nm diode laser with power of 10
      watts) through lacrimal canaliculi with the help of a cannula and fiber optic
      cable. The interior of the nasal cavity was visualized with the help of the nasal
      endoscope on a monitor. Success of procedure was assessed by patency of the
      lacrimal drainage system on irrigation. RESULTS: We performed 56 successive T
      ECLAD. The average procedure time was 10 min, and on an average 235 Joules of
      laser energy was needed. We observed a patent nasolacrimal duct on irrigation in
      39 out of 56 treated eyes. 1 patient had partial, 5 patients had blocked
      irrigation, and 10 patients did not return for follow up. This yields a success
      rate of 69.6% (if we exclude patients who did not return for follow up) with an
      average follow-up period of 6 months. CONCLUSIONS: The 980-nm T-ECLAD is a new
      contribution to the field of lacrimal surgery. It is a minimally invasive and
      quick procedure.

PMID- 24082669
TI  - A comparative study of two methods of optic disc evaluation in patients of
      glaucoma.
AB  - INTRODUCTION: Glaucoma is a progressive disorder and requires serial evaluation
      in order to monitor disease progression and optimize therapy. OBJECTIVE: The
      objective of this study was to determine the correlation between each of cup/disc
      (C/D) ratio and the disc damage likelihood scale (DDLS) with retinal nerve fiber
      layer (RNFL) and global indices in Humphrey field analyzer II (HFA II). DESIGN:
      Cross-sectional study. MATERIALS AND METHODS: A total of 50 patients diagnosed
      with primary open angle glaucoma were examined to grade DDLS score and C/D ratio.
      The average (avg) RNFL was obtained using the Fast RNFL protocol on optical
      coherence tomography (OCT) (4.0.2 Carl Zeiss). HFA II Swedish Interactive
      Threshold Algorithm Standard 24-2 visual fields were obtained within 1 month of
      clinical examination. The correlation of C/D ratio with avg RNFL thickness, Mean
      deviation and Pattern standard deviation was calculated by Pearson correlation
      coefficient (r). Similar coefficients were obtained for DDLS. RESULTS: The P
      value for the difference in the r between C/D ratio with RNFL (-0.628) and DDLS
      with RNFL (-0.8369) was significant (P < 0.01) when correlation of C/D, DDLS with
      RNFL was considered. CONCLUSION: The DDLS shows stronger correlation with
      structural changes in OCT than C/D ratio. The disc diameter and rim width
      increases the value of clinical optic disc examination.

PMID- 24082670
TI  - Complimentary imaging technologies in blunt ocular trauma.
AB  - We describe complimentary imaging technologies in traumatic chorioretinal injury.
      Color and fundus autofluorescence (FAF) images were obtained with a non-mydriatic
      retinal camera. Optical coherence tomography (OCT) helped obtain detailed images
      of retinal structure. Microperimetry was used to evaluate the visual function. A
      40-year-old man sustained blunt ocular trauma with a stone. Color fundus image
      showed a large chorioretinal scar in the macula. Software filters allowed
      detailed illustration of extensive macular fibrosis. A 58-year-old man presented
      with blunt force trauma with a tennis ball. Color fundus imaging showed a
      crescentric area of macular choroidal rupture with fibrosis. FAF imaging
      delineated an area of hypofluorescence greater on fundus imaging. OCT showed
      chorioretinal atrophy in the macula. Microperimetry delineated an absolute
      scotoma with no response to maximal stimuli. Fundus imaging with digital filters
      and FAF illustrated the full extent of chorioretinal injury, while OCT and
      microperimetry corroborated the structure and function correlations. 

PMID- 24082671
TI  - Surgery for macular holes associated with unusual concomitant pathologies.
AB  - Macular hole (MH) is uncommonly seen in association with retinitis pigmentosa
      (RP), optic disc pit or choroidal coloboma. The visual disability in eyes with
      RP, optic disc pit or choroidal coloboma can range from mild to severe. However,
      the macula may not be involved in the primary pathology and hence, the central
      vision may be preserved in these eyes. If a MH develops in such eyes the central
      vision is lost, making the patient severely vision disabled. A perceived poor
      prognosis in such patients may lead to no intervention. However, an attempt
      should be made to repair and restore the macula in these situations in order to
      conserve the vision and limit disability. These eyes can however pose unique
      surgical challenges. We report our experiences of operating on cases of MH
      associated with unusual concomitant pathologies such as RP, choroidal coloboma,
      and optic pit. The outcomes and the surgical challenges differed greatly from the
      conventional idiopathic MH surgery. 

PMID- 24082672
TI  - American joint committee on cancer staging of uveal melanoma.
AB  - In January 2010, the American Joint Committee on Cancer (AJCC) updated its
      staging criteria for uveal melanoma. Here, we discuss the staging classifications
      and evaluate an interesting case to demonstrate. The development of a uniform
      means of staging cancer, such as defined by the AJCC, is critical for information
      sharing among the research community. 

PMID- 24082673
TI  - Leber's miliary aneurysms.
AB  - Leber's disease is a form of primary retinal telangiectasia characterized by the
      presence of abnormalities in the retinal vasculature. It is an idiopathic,
      unilateral condition with male predilection. It is not associated with any other
      systemic or ocular disease. The disease has a very slow progression and can be
      complicated by vascular dilatations, neovascularizations, thromboses,
      retrovitreal hemorrhages, and macular changes. We present a case of Leber's
      miliary aneurysms in an asymptomatic 22-year-old male patient. His fundus
      examination showed aneurysmal dilatations with lipid exudation. Intravenous
      fluorescein angiography showed early and late leakage as well as capillary
      dropout with late hypofluorescence. In this case, the patient was treated with
      laser photocoagulation of the retina. 

PMID- 24082674
TI  - Keratomycosis after incidental spillage of vegetative material into the eye:
      Report of two cases.
AB  - Fungal corneal ulcers mostly occur after incidental corneal trauma by plant
      leaves in farm lands or the use of topical corticosteroids or antibiotics. The
      infection is more prevalent among farmers and harvesters and in some parts of the
      world is considered as an occupational disease; however, there have been a few
      reports on the occurrence of such ulcers in healthy individuals after incidental
      spillage of vegetative material into the eye. The importance of these ulcers is
      their long-term and refractory course, which makes the visual prognosis
      unfavorable in most patients, even after appropriate antifungal therapy or ocular
      interventions. Herein, we present two rare cases of fungal ulcers caused by
      incidental spillage of vegetative material into the eye while eating nuts and
      corn. We also discuss the diagnostic and therapeutic approaches, as well as
      visual outcome reviewing the relevant literature. 

PMID- 24082675
TI  - Posterior sub-Tenon's triamcinolone in choroidal granuloma due to probable ocular
      sarcoidosis.

PMID- 24082676
TI  - Asymmetric presentations of familial exudative vitreoretinopathy.

PMID- 24082677
TI  - Infant with visual inattention and nystagmus.

PMID- 24082678
TI  - Papillary adenocarcinoma of ciliary body.

PMID- 24082679
TI  - Walker Warburg syndrome associated with microphthalmos and megalophthalmos: A
      rare combination.

PMID- 24082680
TI  - Macular hole developing in a post-vitrectomized eye and its surgical outcome.

PMID- 24082681
TI  - Relevance of Goel's hypothesis regarding pathogenesis of degenerative spondylosis
      and its implications on facet distraction surgery.

PMID- 24082682
TI  - The long time follow-up of craniovertebral junction fixation in patients with
      rheumatoid arthritis.
AB  - BACKGROUND: Rheumatoid arthritis (RA) can have very destructive effects,
      especially in the cervical spine. Bone quality is poor in these patients. The
      purpose of this study is to evaluate the feasibility of fusion and accuracy of
      fluoroscopy in cervical transpedicular fixation (CPF) in a standardized clinical
      protocol for RA patients. MATERIALS AND METHODS: 96 pedicles of 15 patients
      operated between January 2000 and ay 2010 due to atlanto-axial and subaxial
      cervical subluxation were investigated for post-operative malposition of the
      transpedicular screws. Three-dimensional computed tomography was used as a useful
      tool in preoperative planning and in transarticular or transpedicular screw
      placement with the free hand technique in the cervical spine of RA patients.
      Fixation and reduction with fusion was performed in all of the patients, and
      autogrefts from iliac wing were used for fusion. Ranawat's and Nurick scales were
      used to assess the results. All screws were evaluated by Kast's criteria. Fusion
      or stability was evaluated on plain radiographs taken 3 weeks and 6, 12 and 60
      months after the surgery. RESULTS: Female to male ratio was 6/9. The mean age at
      the time of surgery was 57.4 years (range 44-72 years). Five of the patients were
      operated for both C1-2 and subaxial subluxation. Two of the 15 patients had only
      C1-2 subluxation and the remaining eight patients had only subaxial cervical
      subluxation. The screws were at their correct places in 84 pedicles (87.5.%)
      while minor breach was detected in 9 (10.9%). According to Ranawat's criteria,
      seven patients remained the same, and eight patients showed improvement.
      Instrumentation failure, loss of reduction or non-union was not observed at the
      final follow-up (average 31.5 months; range 24-60 months). CONCLUSION: CPF
      provides a very strong three column stabilization and solid fusion in the
      osteoporotic vertebrae, but also carries a risk of vascular injury without nerve
      damage or in the RA patients, but the risk is low in experienced hands.

PMID- 24082683
TI  - New perspective for third generation percutaneous vertebral augmentation
      procedures: Preliminary results at 12 months.
AB  - INTRODUCTION: The prevalence of osteoporotic vertebral fractures (OVF) increased
      in the last years. Compression fractures promote a progressive spine kyphosis
      increase, resulting in a weight shift and anterior column overload, with OVF
      additional risk (domino effect). The aim of this study is to evaluate the OVF
      treatment outcome using Spine Jack((r)), a titanium device for third generation
      percutaneous vertebral augmentation procedures (PVAPs). MATERIALS AND METHODS:
      From February 2010, a prospective randomized study was performed examining 300
      patients who underwent PVAP due to OVF type A1 according to Magerl/AO spine
      classification. Patients enrolled in the study were divided in two homogenous
      groups with regards to age (65-85 years), sex, and general clinical findings.
      Group A included 150 patients who underwent PVAP using Spine Jack((r)) system;
      the second, group B (control group), included 150 patients treated by
      conventional balloon kyphoplasty. Patients underwent a clinical (visual analogue
      scale and Oswestry disability index) and radiographic follow-up, with post
      operative standing plain radiogram of the spine at 1, 6, and 12 months. The
      radiographic parameters that were taken into account were: Post-operative
      anterior vertebral body height, pre-operative anterior vertebral body height,
      cephalic anterior vertebral body height, and caudal anterior vertebral body
      height. RESULTS: Compared to the Spine Jack((r)) group, the kyphoplasty group
      required a little longer operation time (an average of 40 min-group A vs. 45 min
      group B, P < 0.05) and a greater amount of polymethylmethacrylate (4.0 mL-group A
      vs. 5.0 mL-group B, P < 0.05;). The post-operative increase in vertebral body
      height was greater in the Spine Jack((r)) group than in the kyphoplasty group (P
      < 0.05). DISCUSSION: PVAP are based on the cement injection into the vertebral
      body. Vertebroplasty does not allow the vertebral body height recovery. Balloon
      kyphoplasty allows a temporary height restoration. Spine Jack((r)) has some new
      features compared to other systems: It is equipped with a mechanical and not a
      hydraulic opening control; this ensures a gradual and controlled vertebral
      fracture reduction. CONCLUSIONS: In our study, we demonstrated that the third
      generation PVAP with Spine Jack((r)) is able to determine a safe vertebral body
      height restoration compared to the conventional balloon kyphoplasty.

PMID- 24082684
TI  - Integrated intervertebral device for anterior cervical fusion: An initial
      experience.
AB  - OBJECTIVE: To analyze the clinical and radiographic results following the use of
      integrated intervertebral implant in patients with cervical spine degenerative
      disease. BACKGROUND: Though excellent results have been reported following
      anterior cervical discectomy and fusion using iliac crest autograft/allograft
      with plating, the morbidity associated with autograft harvest and small chances
      of complications with plating always exists. Recently, there has been development
      of a cervical stand-alone cage with integrated fixation for cervical fusion and
      stabilization with a possible low morbidity and optimal clinical outcome.
      MATERIALS AND METHODS: A retrospective study of 16 patients who underwent
      anterior cervical discectomy and fusion using the integrated intervertebral
      device was performed. Intra-operative parameters, clinical features [Neck
      Disability Index (NDI), visual analog scale (VAS) score for neck/arm pain], and
      presence or absence of dysphagia was recorded. Radiographs were evaluated for
      assessment of implant failure and fusion. RESULTS: Mean age of patients was 54
      years (range: 38-84 years) with male: female ratio of 1:3. Follow-up ranged from
      6 to 12 months (mean: 10 months). In the early postoperative period, 2 of the 15
      patients (13%) patients had mild dysphagia that resolved during follow-up with no
      patient having complaints of dysphagia at 3-month follow-up. One of the patients
      with diffuse idiopathic skeletal hyperostosis (DISH) and severe preoperative
      dysphagia had significant improvement in swallowing function at 3-month follow-up
      that was stable at 1-year follow-up. There was no evidence of implant failure,
      with fusion occurring in 95% (19/20) of operated levels. Analysis of follow-up
      VAS and NDI scores showed significant reduction in VAS score for neck pain (P <
      0.019), radicular arm pain (P < 0.003), and NDI score (P < 0.007) in 77, 92, and
      77% of patients, respectively, at a mean follow-up of 10 months (6-12 months).
      CONCLUSIONS: Our preliminary results with the use of this cervical stand-alone
      anterior fusion device with integrated screw fixation show its efficacy in
      anterior cervical decompression and fusion with stabilization with optimal
      clinical and radiographic outcome. Lower chances of dysphagia with no device
      related complications are appealing, which needs to be verified in larger
      studies.

PMID- 24082685
TI  - Primary spinal intradural extramedullary lymphoma causing cauda equina syndrome.
AB  - We report a case of lumbar intradural extramedullary lesion in an 11-year-old boy
      who presented with cauda equina syndrome and acute bladder disturbance. He
      underwent emergency surgical resection of the lesion, which was proved to be a
      lymphoma by histopathology and immunohistochemistry. He has improved
      neurologically and after 1 year, he is leading a normal life with near normal
      neurological functions. This is the second case of primary spinal intradural
      extramedullary lymphoma. This is the first such case in the pediatric age group
      and causing cauda equina syndrome. We describe the characteristics of such tumors
      along with pathogenesis and management. 

PMID- 24082686
TI  - C1-C3 lateral mass fusion for type IIa and type III Hangman's fracture.
AB  - Hangman's fractures, also known as traumatic spondylolisthesis of axis, can be
      managed either conservatively with immobilization or by surgery. Surgery is
      usually indicated in cases with instability or failure of conservative treatment.
      Different surgical approaches, both anterior and posterior, have been described
      for treating Hangman's fracture. We report two patients, one with type IIa and
      another with type III Hangman's fracture treated with C1-C3 lateral mass fusion
      and discuss the advantages and limitations of this technique when compared to
      other techniques for fusion in patients with Hangman's fracture. 

PMID- 24082687
TI  - Giant cell tumor of dorsal vertebral body.
AB  - A 30-year-old female patient presented with complaints of backache, weakness in
      both lower limbs and bladder/bowel dysfunction. Imaging showed an osteolytic
      lesion at tenth dorsal (D10) vertebra with anterior compression on the spinal
      cord. Complete intralesional tumor excision with reconstruction was carried out
      using the anterolateral extrapleural approach. Histopathological examination was
      suggestive of giant cell tumor (GCT). Because of complete intralesional tumor
      excision and fear of post-radiation osteonecrosis of bone used for delayed bony
      union, a conservative approach was used, and radiation therapy was not given.
      After one year of follow-up patient is doing well without any recurrence of the
      tumor and is ambulant with support. GCT of dorsal vertebral body is an uncommon
      entity and total en bloc excision is difficult. Therefore, the treatment strategy
      is not well-defined. We discuss in brief about incidence, presentation and
      various treatment modalities available for spinal GCT. 

PMID- 24082688
TI  - Intraosseouss degenerative cyst of the axis approached via transcervical
      extrapharyngeal avenue.
AB  - Intraosseous degenerative cysts (IDC) of the cervical spine are rare. IDC within
      C2 have been reported in three articles only. We report a patient with neck pain
      due to a IDC within C2. We discuss the differential diagnosis of these lesions
      and the surgical approaches to reach this complex anatomical region. 

PMID- 24082689
TI  - Lumbosacral arachnoid cyst with tethered cord: A rare case report.
AB  - Arachnoid cysts are cerebrospinal fluid collections in the spine that can present
      with neurological symptoms or be discovered accidentally. Intradural location of
      such cysts especially in the lumbosacral region is relatively rare. The
      association of such cysts with other congenital anomalies such as tethered cord
      lends evidence to the developmental origin of arachnoid cysts. We report a case
      of lumbosacral arachnoid cyst with tethered cord in a 6-year-old male child and
      discuss the etiopathogenesis and management options. 

PMID- 24082690
TI  - Spinal hydatid with meralgia paresthetica in a female: A rare case report.
AB  - Meralgia paresthetica presents as tingling sensation in the antero-lateral aspect
      of thigh. It occurs due to compression of the lateral cutaneous nerve of thigh.
      Proximal spinal lesions may present as meralgia paresthetica due to
      radiculopathy. We present a rare case of spinal hydatid with meralgia
      paresthetica. 

PMID- 24082691
TI  - Updates on drug bioavailability and delivery to posterior segment of eye.

PMID- 24082692
TI  - Recent advance technique for ocular drug delivery by Gupta et al.: Nanoparticle
      laden in situ gel.

PMID- 24082694
TI  - Stability-indicating assay of repaglinide in bulk and optimized nanoemulsion by
      validated high performance thin layer chromatography technique.
AB  - A sensitive, selective, precise and stability-indicating high-performance thin
      layer chromatographic (HPTLC) method for analysis of repaglinide both as a bulk
      drug and in nanoemulsion formulation was developed and validated. The method
      employed TLC aluminum plates precoated with silica gel 60F-254 as the stationary
      phase. The solvent system consisted of chloroform/methanol/ammonia/glacial acetic
      acid (7.5:1.5:0.9:0.1, v/v/v/v). This system was found to give compact spots for
      repaglinide (R f value of 0.38 +/- 0.02). Repaglinide was subjected to acid and
      alkali hydrolysis, oxidation, photodegradation and dry heat treatment. Also, the
      degraded products were well separated from the pure drug. Densitometric analysis
      of repaglinide was carried out in the absorbance mode at 240 nm. The linear
      regression data for the calibration plots showed good linear relationship with r
      (2)= 0.998 +/- 0.032 in the concentration range of 50-800 ng. The method was
      validated for precision, accuracy as recovery, robustness and specificity. The
      limits of detection and quantitation were 0.023 and 0.069 ng per spot,
      respectively. The drug undergoes degradation under acidic and basic conditions,
      oxidation and dry heat treatment. All the peaks of the degraded product were
      resolved from the standard drug with significantly different R f values.
      Statistical analysis proves that the method is reproducible and selective for the
      estimation of the said drug. As the method could effectively separate the drug
      from its degradation products, it can be employed as a stability-indicating one.
      Moreover, the proposed HPTLC method was utilized to investigate the degradation
      kinetics in 1M NaOH. 

PMID- 24082693
TI  - Effect of maxillary sinus floor augmentation without bone grafts.
AB  - OBJECTIVE: The objective of the present review was to determine the effectiveness
      of maxillary sinus floor augmentation without bone grafts using lateral window
      technique. MATERIALS AND METHODS: PubMed and Cochrane databases were searched for
      relevant articles. We also included articles by hand search until June 2012. The
      analysis included both human and animal studies which satisfied the following
      criteria: Minimum of 6 months follow-up, no use of bone grafts, and lateral
      window approach to the sinus. RESULTS: We included 22 articles in the review. A
      descriptive analysis of the constructed evidence tables indicated that there is
      evidence of predictable a mount of bone formation in the maxillary sinus
      augmentation without the use of bone grafts. CONCLUSION: Within the limits of the
      articles and data available, maxillary sinus augmentation without bone graft
      might be considered effective inpredictable bone formation.

PMID- 24082695
TI  - Development and evaluation of fixed dose bi therapy sublingual tablets for
      treatment stress hypertension and anxiety.
AB  - OBJECTIVE: A stress induced rise in the blood pressure. Some believe that
      patients with hypertension are characterized by a generalized state of increased
      anxiety. AIM: The purpose of this study is to prepare a fixed dose bi therapy
      using bisoprolol hemifumarate (BH) as antihypertensive drug and buspirone
      hydrochloride (BuHCl) as anxiolytic drug, which can be used to treat both
      diseases concomitantly. Using sublingual tablets is hopeful to improve the BuHCl
      poor oral bioavailability and to facilitate administration to patients
      experiencing problems with swallowing. MATERIALS AND METHODS: A total of 5mg BH
      and 10mg BuHCl were selected based on compatibility study. A 3*22 full factorial
      design was adopted for the optimization of the tablets prepared by direct
      compression method. The effects of the filler type, the binder molecular weight,
      and the binder type were studied. The prepared formulae were evaluated according
      to their physical characters as hardness, friability, disintegration time (new
      modified method and in vivo disintegration time) and wetting properties. In vitro
      drugs dissolute, permeation through the buccal mucosa and the effect of storage
      were analyzed by a new valid high pressure liquid chromatography (HPLC) method.
      Bioavailability study of the selected formula study was carried out and followed
      by the clinical. RESULTS: The optimized tablet formulation showed accepted
      average weight, hardness, wetting time, friability, content uniformity,
      disintegration time (less than 3 min). Maximum drug release could be achieved
      with in 10 min. In addition enhancing drug permeation through the buccal mucosa
      and, the maximum concentration of the drug that reached the blood was in the
      first 10 min which means a rapid onset of action and improved the extent of both
      drug's absorption. CONCLUSION: The results revealed that sublingual (F6) tablets
      containing both drugs would maintain rapid onset of action, and increase
      bioavailability. BuHCl with BH can be attributed to the marked decline in DBP and
      SBP. That led to a reduction in the MAP.

PMID- 24082696
TI  - Development and validation of spectrophotometric methods for simultaneous
      estimation of citicoline and piracetam in tablet dosage form.
AB  - CONTEXT: Citicoline (CN) and piracetam (PM) combination in tablet formulation is
      newly introduced in market. It is necessary to develop suitable quality control
      methods for rapid and accurate determination of these drugs. AIM: The study aimed
      to develop the methods for simultaneous determination of CN and PM in combined
      dosage form. MATERIALS AND METHODS: The first method was developed by formation
      and solving simultaneous equations using 280.3 and 264.1 nm as two analytical
      wavelengths. Second method was absorbance ratio in which wavelengths selected
      were 256.6 nm as its absorptive point and 280.3 nm as lambdamax of CN. According
      to International Conference on Harmonization (ICH) norm, the parameters -
      linearity, precision, and accuracy were studied. The methods were validated
      statistically and by recovery studies. RESULTS: Both the drugs obeyed Beer
      Lambert's law at the selected wavelengths in concentration range of 5-13 MUg/ml
      for CN and 10-22 MUg/ml for PM. The percentage of CN and PM in marketed tablet
      formulation was found to be 99.006 +/- 0.173 and 99.257 +/- 0.613, respectively;
      by simultaneous equation method. For Q-Absorption ratio method the percentage of
      CN and PM was found to be 99.078 +/- 0.158 and 99.708 +/- 0.838, respectively.
      CONCLUSIONS: The proposed methods were simple, reproducible, precise and robust.
      The methods can be successfully applied for routine analysis of tablets.

PMID- 24082697
TI  - Tobacco addiction augments obesity and carcinogenesis: Matter of concern for
      Indian patients.
AB  - PURPOSE: Life-style and tobacco addiction is the major risk factors for cancer
      progression in all over the world. Knowledge gaps between tobacco addiction,
      obesity and cancer in Indian patients brought an interdisciplinary group of
      investigators together to discuss the present study. PATIENTS AND METHODS: We
      calculated the body mass index (BMI) of all the patients (N = 927) who were
      diagnosed with cancer for its treatment. National Institutes of Health (NIH)
      criteria were used to categorize the patients. All the patients of this disease
      could be contacted in person to find out the history of the disease. RESULTS: The
      frequency of addiction in urban cancer patient was found to be about 53.3% and in
      a rural area it was only 33.7%. Tobacco addiction was independently associated
      with younger age of cancer patient (odds ratio [OR] 2.242; 95% Confidence
      interval (CI) 1.653-3.042), obese (OR 7.433; 95% CI 3.746-14.750), overweight (OR
      4.676; 95% CI 3.381-6.468) and advanced stage of cancer (OR 11.950; 95% CI 5.283
      27.030). CONCLUSION: Tobacco consumption appears to be a major contributor to
      cancer in younger age with elevated BMI in India. Rapid changes in diet and life
      style, increase in tobacco consumption appear to be strongly associated with the
      carcinoma in this middle-income country.

PMID- 24082698
TI  - In vitro antioxidant and H(+), K(+)-ATPase inhibition activities of Acalypha
      wilkesiana foliage extract.
AB  - AIMS: The aim of this study was to evaluate the antioxidant activty and anti-acid
      property of Acalypha wilkesiana foliage extract. MATERIALS AND METHODS: Hot and
      cold aqueous extracts were prepared from healthy leaves of A. wilkesiana. Free
      radical scavenging activity and H(+), K(+)-ATPase inhibition activities of
      aqueous foliage extracts was screened by in vitro models. STATISTICAL ANALYSIS
      USED: All experiments were performed in triplicate and results are expressed as
      mean +/- SEM. RESULTS: A. wilkesiana hot aqueous extract (AWHE) showed
      significant antioxidants and free radical scavenging activity. Further, AWHE has
      shown a potent H(+), K(+)-ATPase inhibitory activity (IC50: 51.5 +/- 0.28 MUg/ml)
      when compare to standard proton pump inhibitor omeprazole (56.2 +/- 0.64 MUg/ml);
      however, latter activity is equal to A. wilkesiana cold aqueous extract (AWCE).
      Quantitative analysis of AWHE has revealed more content of phenols and
      flavonoids; this is found to be the reason for good antioxidant activity over
      AWCE. Molecular docking was carried out against H(+), K(+)-ATPase enzyme crystal
      structure to validate the anti-acid activity of A. wilkesiana major
      phytochemicals. CONCLUSIONS: The present study indicates that the constituents of
      AWHE and AWCE have good antacid and free radical scavenging activity.

PMID- 24082699
TI  - Adverse drug reactions reporting : Knowledge and opinion of general public in
      Penang, Malaysia.
AB  - OBJECTIVE: The objective of this study was to explore the knowledge of the
      general population towards ADR and their reporting system. METHODS: An anonymous,
      self-administered questionnaire (15 items) was designed. The questionnaire was
      subjected to face validity and content validity. The reliability coefficient was
      found to be 0.71. This study recruited proportionately large convenience sample
      of the general public in Penang. Interviews using a structured questionnaire were
      conducted over a week period in August 2009. The recommended sample size was
      calculated to be 368. RESULTS: Three hundred thirty-four responses were received.
      Slightly more than half of the respondents were in the age group of 18-25 years
      (53.6%; n = 179). When asked about the sources of their medication majority of
      them reported medical doctor (85.6%), whereas small number (34.7%) reported
      community pharmacists as sources of medications. Three-quarter of the respondents
      (77.2%) get their information about the side-effects of drugs from physicians,
      followed by pharmacist (44.6%). More than half of the respondents (65.6%, n =
      219) reported unawareness about the existence of ADR center set up by the
      Ministry of Health. CONCLUSION: Respondents reflected inadequate knowledge on ADR
      reporting. This needs to be corrected as the trend of future pharmacovigilance is
      toward the patient. Moreover, the new trend seems to be more appropriate as the
      patient is the group of the people who are directly affected from the ADR of a
      particular drug and not the health-care providers. Furthermore, the patient will
      be informed about the economic implications of not reporting ADR. It is
      recommended that government agencies, like MADRAC needs to find ways to increase
      patient- reported ADR cases.

PMID- 24082700
TI  - Anti-obesity activity of chloroform-methanol extract of Premna integrifolia in
      mice fed with cafeteria diet.
AB  - AIM OF THE STUDY: Aim of the present study was to evaluate the anti-obesity
      activity of chloroform:methanol extract of P. integrifolia (CMPI) in mice fed
      with cafeteria diet. MATERIALS AND METHODS: Female Swiss Albino mice were divided
      into six groups, which received normal and cafeteria diet, standard drug
      simvastatin (10 mg/kg) and CMPI (50, 100 and 200 mg/kg) daily for 40 days.
      Parameters such as body weight, body mass index (BMI), Lee index of obesity
      (LIO), food consumption, locomotor behavior, serum glucose, triglyceride, total
      cholesterol, high density lipoprotein (HDL), low density lipoprotein (LDL), very
      low density lipoprotein (VLDL), atherogenic index, organ weight and organ fat pad
      weight were studied for evaluating the anti-obesity activity of P. integrifolia.
      High performance liquid chromatography (HPLC) fingerprint profile of chloroform
      methanol extract was also studied using quercetin as the reference standard.
      RESULTS: There was a significant increase in body weight, BMI, LIO, food
      consumption, organ weight (liver and small intestine), organ fat pad weight
      (mesenteric and peri-renal fat pad) and in the levels of serum glucose,
      triglyceride, total cholesterol, LDL and VLDL with a significant decrease in
      locomotor behavior (ambulation, rearing, grooming) and HDL level in cafeteria
      diet group. Animals treated with CMPI showed dose dependent activity. P.
      integrifolia (200 mg/kg) supplementation attenuated all the above alterations,
      which indicates the anti-obesity activity. HPLC fingerprint profile of CMPI
      showed two peaks in the solvent system of 50 mm potassium diphosphate (pH-3 with
      ortho phosphoric acid): Methanol (30:70 v/v) at 360 nm. CONCLUSION: Present
      findings suggest that, CMPI possessed anti-obesity activity that substantiated
      its ethno-medicinal use in the treatment of obesity.

PMID- 24082701
TI  - Cytochrome P450 2C9 gene polymorphism in phenytoin induced gingival enlargement:
      A case report.
AB  - Gingival enlargement comprises any clinical condition in which an increase in the
      size of the gingiva is observed. Among the drugs that induce gingival
      enlargement, the antiepileptic agent phenytoin has been widely related to this
      condition. The Cytochrome P450(CYP) superfamily is the most commonly involved
      enzymes in metabolism of drugs. Common coding region CYP variants that affects
      drug elimination and response has been studied in great detail. Pharmacogenetic
      influences on drug metabolism have been widely reviewed and gene polymorphism of
      cytochrome P450 2C9 appeared to be responsible for much of the interindividual
      variability on drug elimination. Genetic variation in the CYP2C9 gene can affect
      metabolism, leading to altered phenotypes. Individuals with poor metaboliser
      alleles of CYP2C9 gene were shown to have a reduced metabolism of phenytoin
      compared with wild-type alleles. Thus identification of patients genotype prior
      to anti-epileptic drug administration could potentially prevent higher serum drug
      concentrations leading to adverse side effects such as gingival enlargement. This
      case report addresses the influence of CYP2C9 genetic polymorphism on Phenytoin
      drug metabolism thereby causing gingival enlargement. 

PMID- 24082702
TI  - Submandibular sialolithiasis: Report of six cases.

PMID- 24082703
TI  - Pleiotropy of chemically modified tetracycline in periodontitis.

PMID- 24082704
TI  - A medico-legal case of irresponsiveness to antibiotic therapy: A point that
      should not be forgotten.

PMID- 24082705
TI  - Indian Menopause Society guidelines.

PMID- 24082706
TI  - An Indian perspective on mid-life management.

PMID- 24082707
TI  - Clinical practice guidelines on menopause: An executive summary and
      recommendations.

PMID- 24082709
TI  - Commentary on guidelines on osteoporosis and menopause - Indian Menopause
      Society.

PMID- 24082708
TI  - Clinical practice guidelines on postmenopausal osteoporosis: An executive summary
      and recommendations.

PMID- 24082710
TI  - Commentary on guidelines on postmenopausal osteoporosis - Indian Menopause
      Society.

PMID- 24082711
TI  - Commentary on guidelines on postmenopausal osteoporosis - Indian Menopause
      Society.

PMID- 24082713
TI  - Editor'S comment.

PMID- 24082714
TI  - Rise in polluters of scientific research: How to curtail information pollution
      (infollution).

PMID- 24082712
TI  - Commentary on guidelines on postmenopausal osteoporosis - Indian Menopause
      Society.

PMID- 24082715
TI  - Effect of heavy metals on germination of seeds.
AB  - With the expansion of the world population, the environmental pollution and
      toxicity by chemicals raises concern. Rapid industrialization and urbanization
      processes has led to the incorporation of pollutants such as pesticides,
      petroleum products, acids and heavy metals in the natural resources like soil,
      water and air thus degrading not only the quality of the environment, but also
      affecting both plants and animals. Heavy metals including lead, nickel, cadmium,
      copper, cobalt, chromium and mercury are important environmental pollutants that
      cause toxic effects to plants; thus, lessening productivity and posing dangerous
      threats to the agro-ecosystems. They act as stress to plants and affect the plant
      physiology. In this review, we have summarized the effects of heavy metals on
      seeds of different plants affecting the germination process. Although reports
      exist on mechanisms by which the heavy metals act as stress and how plants have
      learnt to overcome, the future scope of this review remains in excavating the
      signaling mechanisms in germinating seeds in response to heavy metal stress. 

PMID- 24082716
TI  - A chemogenomics based approach for deorphanization of testicular receptor 4: An
      orphan receptor of nuclear receptor superfamily.
AB  - Orphan Receptor of Nuclear Receptor superfamily is the one with no known
      endogenous ligands. Many of these orphan receptors are associated with different
      types of diseases and therefore deserve special attention to find the potential
      ligands they would be associated with. The major task of molecular pharmacology
      is the deorphanization of the large number of nuclear receptors with unidentified
      endogenous agonists. The deorphanization provides a promising research for new
      therapeutics. The Testicular Receptor 4 being negative modulator to other members
      of the nuclear receptor superfamily, is one of the Orphan members of this family
      and is associated with prostate cancer, breast cancer, sickle cell anemia and
      joint diseases. The knowledge that related receptors of the same family often
      have ligands with similar structural features has helped us to utilize the
      chemogenomic approach to deorphanize the orphan receptor. Chemogenomics approach
      involves screening of known ligands of a protein family having analogous domain
      architecture for identification of new leads for existing protein family members.
      The deorphanization involved the database homology searching, followed by domain
      identification, active site prediction, sequence and structure comparative
      studies. A ligand library set was prepared based on these studies and was used to
      deorphanize the receptor. The molecular docking study conducted using PyRx
      revealed that estradiol and tretinion as a potential ligand for Testicular
      Receptor 4. 

PMID- 24082717
TI  - Odontogenic keratocyst: What is in the name?
AB  - The classification of odontogenic cysts is complicated and can create confusion
      for both clinicians and pathologists. The odontogenic keratocyst (OKC) is an
      enigmatic developmental cyst that deserves special attention. It has
      characteristic histopathological and clinical features; but, what makes this cyst
      special is its aggressive behavior and high recurrence rate. Despite of many
      classifications and nomenclature, unfortunately the clinicians still have to face
      difficulties in the management of this commonly found jaw lesion. This article is
      an effort to provide an overview of various aspects of OKC with emphasis on
      nomenclature, recurrence, molecular aspects, and management of OKC. 

PMID- 24082718
TI  - Antimicrobial resistance in India: A review.
AB  - Antimicrobial resistance is an important concern for the public health
      authorities at global level. However, in developing countries like India, recent
      hospital and some community based data showed increase in burden of antimicrobial
      resistance. Research related to antimicrobial use, determinants and development
      of antimicrobial resistance, regional variation and interventional strategies
      according to the existing health care situation in each country is a big
      challenge. This paper discusses the situational analysis of antimicrobial
      resistance with respect to its problem, determinants and challenges ahead with
      strategies required in future to reduce the burden in India. Recent data from
      Google search, Medline and other sources were collected which was reviewed and
      analyzed by the authors. Hospital based studies showed higher and varied spectrum
      of resistance in different regions while there are limited number of community
      based studies at country level. There exists lacunae in the structure and
      functioning of public health care delivery system with regard to quantification
      of the problem and various determining factors related to antimicrobial
      resistance. There is an urgent need to develop and strengthen antimicrobial
      policy, standard treatment guidelines, national plan for containment of AMR and
      research related to public health aspects of AMR at community and hospital level
      in India. 

PMID- 24082719
TI  - Utilization of dental care: An Indian outlook.
AB  - Oral health has a significant impact on the quality of life, appearance, and self
      esteem of the people. Preventive dental visits help in the early detection and
      treatment of oral diseases. Dental care utilization can be defined as the
      percentage of the population who access dental services over a specified period
      of time. There are reports that dental patients only visit the dentist when in
      pain and never bother to return for follow-up in most cases. To improve oral
      health outcomes an adequate knowledge of the way the individuals use health
      services and the factors predictive of this behavior is essential. The interest
      in developing models explaining the utilization of dental services has increased;
      issues like dental anxiety, price, income, the distance a person had to travel to
      get care, and preference for preservation of teeth are treated as barriers in
      regular dental care. Published materials which pertain to the use of dental
      services by Indian population have been reviewed and analyzed in depth in the
      present study. Dental surgeons and dental health workers have to play an adequate
      role in facilitating public enlightenment that people may appreciate the need for
      regular dental care and make adequate and proper use of the available dental care
      facilities. 

PMID- 24082720
TI  - Tooth positioners and their effects on treatment outcome.
AB  - Malocclusion can also be corrected by means of clear removable appliances called
      as "tooth positioners" or "aligners". A tooth positioner is used to control
      settling and to minimize or eliminate relapse of the teeth after an orthodontic
      treatment. In this article, a complete review of the objectives, course of
      treatment, fabrication, and the materials used for fabrication of tooth
      positioners along with their importance and disadvantages were discussed. Tooth
      positioners did improve the overall orthodontic treatment outcome as quantified
      by the ABO (American Board of orthodontics) objective scoring method. But once
      the initial occlusal contact was achieved, the vertical movement of teeth was
      found to be inhibited. 

PMID- 24082721
TI  - Comparison of the serum iron, ferritin levels and total iron-binding capacity
      between pregnant women with and without gestational diabetes.
AB  - BACKGROUND: Gestational diabetes mellitus (GDM) is the most common metabolic
      disorder during pregnancy. GDM causes substantial morbidity and mortality and
      long- term complications. GDM-related risk factors have not been completely
      identified yet. Some studies have found relationship between increased serum
      ferritin and impaired oral glucose tolerance test but the relationship between
      serum ferritin and risk of GDM has been controversial. The aim of the study was
      to determine serum iron and ferritin levels and total iron binding capacity
      (TIBC) in women with GDM and comparison with normal pregnant women. MATERIALS AND
      METHODS: This case-control study was performed among 200 pregnant women (case =
      100, control = 100) who were referred to Yahya-Nejad Hospital in the second
      trimester in Babol from 2008 to 2009. GDM was diagnosed by impaired OGTT based on
      Carpenter and Coustan criteria. The 2 groups were matched in age, gestational age
      and parity. RESULTS: High serum ferritin level increased the risk of gestational
      diabetes to 2.4-fold [OR = 2.4 (0.83-6.9) CI = 95% (P = 0.10)], while in those
      with low ferritin levels, the risk of developing gestational diabetes was reduced
      to 82% [OR = 0.8 with (0.08-0.37) CI = 95% (P = 0.001)]. Using the logistic
      regression model, after adjustment for BMI, the OR was 2.37 [(0.80-7.01) CI = 95%
      (P = 0.11)] for low ferritin level and OR = 0.20 [(0.09-0.44) CI = 95% (P =
      0.0001)] for high ferritin level, which was statistically significant.
      CONCLUSION: The serum ferritin level was markedly higher in women with
      gestational diabetes than in normal pregnant women; therefore, high ferritin can
      be regarded as a significant risk factor for the development of gestational
      diabetes.

PMID- 24082722
TI  - Bacteriological profile of neonatal septicemia and antibiotic susceptibility
      pattern of the isolates.
AB  - CONTEXT: Septicemia in neonates refers to generalized bacterial infection
      documented by positive blood culture in the first four weeks of life and is one
      of the four leading causes of neonatal mortality and morbidity in India. AIM: To
      isolate and identify the bacterial etiologic agents responsible for neonatal
      sepsis and to determine the susceptibility pattern of isolates in a tertiary care
      hospital in North Karnataka. MATERIALS AND METHODS: Six hundred eighty-three
      blood samples were collected and processed from patients in accordance with
      standard protocols. Antibiotic susceptibility of the isolates was done by disc
      diffusion method according to National Committee for Clinical Laboratory
      Standards (NCCLS) recommendations. RESULTS: Blood culture reports were positive
      in 19.2% cases. Among the culture positive cases, there were 65.5% males and
      34.5% females. Early-onset sepsis was present in 74.8% and late-onset sepsis was
      observed in 25.2% of the cases. Best overall sensitivity among Gram-negative
      isolates was to imipenem (93%), followed by amikacin (52%) and netilmicin (41%).
      Gram-positive isolates had sensitivity of 91% to linezolid, 68% to tetracycline,
      64% to piperacillin/tazobactam erythromycin, and 52% to ciprofloxacin.
      CONCLUSION: Gram-negative organisms (Klebsiella, Acinetobacter), coagulase
      negative staphylococci, and Staphylococcus aureus are the leading cause of
      neonatal sepsis in this study and most of them are resistant to multiple
      antibiotics. Therefore the results of this study suggest that, surveillance of
      antimicrobial resistance in our hospital is necessary.

PMID- 24082723
TI  - Ninety-one cases of ameloblastoma in an Indian population: A comprehensive
      review.
AB  - AIM: To assess the cases of ameloblastoma retrospectively for various parameters.
      MATERIALS AND METHODS: Ninety-one previously reported cases of ameloblastoma from
      Government Dental College and Hospitals, Nagpur, were included in this study.
      Data were collected considering parameters such as age, sex, symptoms,
      radiographic, histopathology, treatment modalities, and recurrence. Our findings
      were also compared with world literature. RESULTS: The average age was 32.5
      years. Mostly men complained of an asymptomatic swelling and duration of less
      than one year. Posterior segment and vertical ramus of mandible was the
      frequently involved site. Radiographically, multilocular appearance was noted
      more than 60% of the cases. Plexiform and unicystic ameloblastoma occurred
      frequently. Surgery was the treatment of choice in this review. Recurrence was
      noted in more than 10% of the cases. CONCLUSION: There are variations in our
      review in comparison to reported literature.

PMID- 24082724
TI  - The role of stroma in the expansion of odontogenic cysts and adenomatoid
      odontogenic tumor: A polarized microscopy study.
AB  - OBJECTIVES: To compare the polarization colors of collagen fibers of odontogenic
      keratocyst (OKC), radicular cyst, dentigerous cyst, and adenomatoid odontogenic
      tumor (AOT) with reference to their biological behavior. STUDY DESIGN: Twenty
      cases each of OKC, radicular cyst, dentigerous cyst, and AOT were stained with
      picrosirius red stain and studied under polarized light. RESULTS: A predominance
      of green to greenish yellow thick fibers was noted in OKC and AOT as compared to
      dentigerous cyst and radicular cyst. There was no significant difference between
      the polarization colors of the thin fibers in all the three groups. CONCLUSION:
      The stroma of OKC and AOT consists of poorly packed or pathologic collagen and
      plays a role in its neoplastic behavior.

PMID- 24082725
TI  - Sexual dysfunction among women with diabetes mellitus in a diabetic center in
      Amol.
AB  - BACKGROUND: Sexual disorders among diabetic men have been proved in different
      studies but sexual dysfunction of diabetic women has received attention only
      recently. Neuropathy, vascular impairment, and psychological complaints have been
      implicated in the pathogenesis of decreased libido, low arousability, decreased
      vaginal lubrication, orgasmic dysfunction, and dyspareunia among diabetic women.
      AIM: The aim of this research was to study the prevalence of sexual dysfunction
      in different areas among diabetic women. MATERIALS AND METHODS: A cross-sectional
      study was conducted on 500 women who were recruited from a diabetes center, based
      on questionnaires completed by them. Data regarding demographic features,
      physical complications, and sexual disorders were obtained. Medical records of
      patients were used to obtain body mass index (BMI) and details of complications.
      RESULTS: Mean age of participants, duration of diabetes, and BMI was 48.8 +/-
      0.4, 8.9 +/- 0.32 years, and 28.9 +/- 0.23, respectively. Prevalence of sexual
      dysfunction was 32.3%. Low sexual desire was seen in 81.8%, disorders of arousal
      in 78.3%, of orgasm in 47.5%, and 35.1% had disorder in resolution area. There
      was no significant relationship between some factors such as age, duration of
      diabetes, BMI, and frequency of sexual dysfunction. Frequency of diabetic
      complications demonstrated a significant effect on the prevalence of sexual
      dysfunction. CONCLUSION: Sexual problems are frequent among diabetic women and
      deserve more attention in clinical practice and researches.

PMID- 24082726
TI  - Prevalence of caries among preschool-aged children in a central Anatolian
      population.
AB  - OBJECTIVE: Early childhood caries (ECC) is a particularly destructive form of
      tooth decay that afflicts young children. The etiology and associated factors of
      ECC should be studied adequately to overcome this health hazard. The aim of this
      study was to determine caries prevalence and its consequences in toddlers in an
      Anatolian city, Kirikkale. MATERIALS AND METHODS: Examinations were performed in
      family medicine centers by three calibrated dentists during a period of 6 months.
      The status of dental caries was recorded according to the World Health
      Organization (WHO) criteria. We recorded the clinical indexes of decayed, missed,
      and filled teeth (DMFT and dmft; upper-case letters refer to permanent and lower
      case letters to primary teeth), and decayed, missed, and filled surfaces (DMFS).
      RESULTS: Totally 3171 toddlers were included (52% males and 48% females). The
      mean age was 25.8 +/- 10.1 months. The prevalence of ECC in preschool children
      was 17.3%, while the mean df(t) was 0.63 +/- 1.79. ECC increased significantly
      with age. Dental caries were mostly observed in primary maxillary central teeth.
      Occlusal and buccal surfaces were the most affected sites. The difference in
      distribution of caries between maxilla and mandibula was found to be
      statistically significant (P < 0.05). CONCLUSIONS: When compared to other data
      obtained from various epidemiologic studies, the toddlers living in Kirikkale
      city center had a significant caries level. This observation had clearly
      suggested that early preventive measures should urgently be put into effect all
      over the city.

PMID- 24082727
TI  - The effects of S-nitrosoglutathione and S-nitroso-N-acetyl-D, L-penicillamine in
      a rat model of pre-eclampsia.
AB  - BACKGROUND: Pre-eclampsia (PE) complicates approximately 5-7% of all pregnancies.
      This study investigates the effects of S-nitroso-N-acetylpenicillamine (SNAP) and
      S-nitrosoglutathione (GSNO) on the classical features of PE. MATERIALS AND
      METHODS: On day 14 of gestation, female Sprague-Dawley rats were separated into
      five groups and treated intravenously for 7 days as follows: (i) 0.3 mL 0.9%
      saline (control, n = 11); (ii) 50 mg/kg Body Weight (BW) N-nitro-L-arginine
      methyl ester (L-NAME) in 0.3 mL saline (n = 10); (iii) 50 mg/kg BW L-NAME and 8
      mg/kg BW GSNO in 0.15 mL saline (n = 6); (iv) 50 mg/kg BW L-NAME in 0.15 mL
      saline and 8 mg/kg BW SNAP in 0.15 mL DMSO (n = 9); and (v) 0.15 mL DMSO and 0.15
      mL saline (SNAP control, n = 7). Blood pressures were measured on day 14 through
      day 20, a 4-h urine sample was taken on day 20, and animals were sacrificed on
      day 21. Pups were counted and weighed individually. RESULTS: SNAP and GSNO
      significantly decreased systolic, diastolic, and mean arterial pressures in PE
      induced rats from day 14 through day 20 (P < 0.05). Pup weights in SNAP and GSNO
      groups were higher than in L-NAME group but lower than in controls (P <= 0.001).
      SNAP and GSNO partially reversed growth retardation. CONCLUSION: Elevated blood
      pressure, proteinuria, and intrauterine growth restriction associated with PE
      were induced in Sprague-Dawley rats using L-NAME. These were partially reversed
      with the use of GSNO and SNAP. The mechanism of action of these S-nitrosothiols
      (RSNOs) should be further explored.

PMID- 24082728
TI  - Effect of high-dose zinc supplementation with oral hypoglycemic agents on
      glycemic control and inflammation in type-2 diabetic nephropathy patients.
AB  - OBJECTIVE: The study aims to evaluate the effect of zinc sulfate on markers of
      glycemic control, lipid profile and inflammation in type-2 diabetes with
      microalbuminuria patients. MATERIALS AND METHODS: Type-2 diabetes with
      microalbuminuria patients on oral hypoglycemic agents (OHA) and angiotensin
      converting enzyme (ACE) inhibitors were selected and divided into 2 groups: One
      group (n = 27) continued with OHA alone, second group (n = 27) was on OHA and in
      addition 50 mg elemental zinc as zinc sulphate supplementation for 12 weeks.
      Fasting, post-prandial blood glucose, glycosylated hemoglobin, lipid profiles,
      inflammatory marker hs-CRP and urine microalbumin were measured. RESULTS: There
      were no significant differences in biochemical status among groups at baseline.
      After receiving zinc, the mean fasting blood glucose (FBS), post-prandial blood
      glucose (PPBS) and glycosylated hemoglobin (HbA1c) were decreased significantly
      (P = 0.0001). Significant decrease was observed in TG (P = 0.002) and VLDL
      cholesterol (P = 0.002), whereas there was no significant decrease in TC and LDL
      cholesterol. The high-density lipoprotein (HDL) cholesterol was significantly (P
      = 0.0001) increased from baseline. Zinc supplementation had significant effects
      in decreasing serum hs-CRP from 10.51 +/- 1.68 mg/L to 7.75 +/- 1.56 mg/L (P =
      0.0001) and microalbumin level from 146.87 +/- 30.83 mg/day to 80.70 +/- 33.99
      mg/day (P = 0.0001). There were no significant changes in the levels of all these
      parameters in OHA group. CONCLUSION: Our results conclude that supplementation of
      zinc improved the effectiveness of OHA and may be beneficial in decreasing blood
      glucose, TG, urinary albumin excretion and inflammation in diabetic nephropathy
      patients and thus reducing the risk of complications.

PMID- 24082729
TI  - Quantitative estimation of sodium, potassium and total protein in saliva of
      diabetic smokers and nonsmokers: A novel study.
AB  - AIMS: The aim of the study was to evaluate the difference in sodium, potassium,
      total protein in whole saliva in diabetic smokers, diabetic nonsmokers and
      healthy controls. MATERIALS AND METHODS: Nonstimulated saliva samples were
      collected from a group of diabetic smokers, diabetic nonsmokers, and controls.
      Supernatant after centrifugation was used to determine the levels of sodium,
      potassium, and total protein by using semiautomatic analyzer. RESULTS: There
      exists a statistical difference in the levels of potassium and total protein
      between diabetic smokers, nondiabetic smokers, and controls. Difference in the
      levels of sodium is only significant with nondiabetic smokers and controls.
      CONCLUSION: Diabetes mellitus is known to alter the composition of saliva. The
      purpose of this study was to estimate and compare the levels of salivary
      potassium, sodium, and total protein in smoker diabetic patients and nondiabetic
      smokers and controls, and to explore potential of salivary electrolytes [Na+, K+]
      and total proteins as markers. The estimated values of salivary constituents add
      to the data already recorded in Indian population. However, further studies using
      large samples are required to evaluate the findings in our study.

PMID- 24082730
TI  - Modified Hodge test: A useful and the low-cost phenotypic method for detection of
      carbapenemase producers in Enterobacteriaceae members.
AB  - BACKGROUND: The global spread of antimicrobial resistance has acquired greater
      significance in the public health perspective. Drug resistance has posed a threat
      for the management of various hospital-acquired infections (HAI). For bacteria
      producing extended spectrum beta lactamase, carbapenems are the drug of choice.
      However, treatment failures are still a cause of concern due to carbapenemase
      producers. AIM: Various phenotypic and genotypic methods are available for the
      detection of carbapenemase producers. Studies thus far have mostly concentrated
      on comparing various methods for detection of carbapenemase producers. We used
      low-cost and the easily performed modified Hodge test (MHT) for detecting the
      carbapenemase producers in Enterobacteriaceae members isolated from various
      clinical specimens. MATERIAL AND METHODS: The study included 1072 clinical
      isolates of Enterobacteriaceae collected in India between April 2008 and February
      2010. MHT was performed on all the isolates in accordance with CDC and CLSI
      guidelines. RESULTS: The carbapenemase activity was detected in 35.9% (385/1072)
      of the isolates. Klebsiella spp. 28.7% (80/278), Citrobacter spp. 20.4% (25/122),
      11.3% (38/334) in E. coli, 20.3% (45/221) in Enterobacter spp., and 16.2% (9/117)
      in Proteus spp. revealed variable resistance activities against carbapenems.
      CONCLUSION: Enterobacteriaceae members are among the most common and easily
      transferable bacterial species responsible for severe HAI. This study revealed a
      high percentage of Enterobacteriaceae clinical isolates producing carbapenemases
      in India. Detection of such bacteria, formulating hospital antibiogram, and
      monitoring the usage of antimicrobial drugs is recommended.

PMID- 24082731
TI  - Immunohistochemical evaluation of oral epithelial dysplasia using cyclin-D1, p27
      and p63 expression as predictors of malignant transformation.
AB  - OBJECTIVE: To evaluate the degree of expression of cyclin-D1, p27 and p63 in
      mild, moderate and severe dysplasia using immunohistochemical evaluation in order
      to illustrate their prognostic value and attempt to propose a molecular grading
      system for oral epithelial dysplasia. MATERIALS AND METHODS: The analysis
      included thirty cases of mild, moderate and severe dysplasia from Department of
      Oral and Maxillofacial Pathology, Saveetha Dental College, Chennai after a
      critical review of the Hematoxylin and Eosin (H and E) stained sections. They
      were subjected to immunohistochemical evaluation using the markers cyclin-D1, p27
      and p63. The assessment of the expression based on staining intensity and
      distribution of immunohistochemical staining of the various markers was analyzed
      followed by statistical analysis. RESULTS: A highly significant increase in the
      expression of cyclin-D1 (P < 0.000) and p63 (P < 0.001) and a moderately
      significant decrease in the expression of p27 (P < 0.012) with the increasing
      severity of dysplasia was observed in our study. CONCLUSIONS: The result of our
      research affirms the fact that the increase in the expression of markers of cell
      cycle regulators such as cyclin D1, decrease in the expression of cell cycle
      inhibitors like p27 and increased expression of p63 in parallel with the
      increasing severity of dysplasia, emphasizes the use of immunohistochemical
      markers cyclin D1, p27 and p63 as prognostic markers for better understanding the
      behaviour of these potentially malignant disorders aiming towards proposing a
      molecular grading system for oral epithelial dysplasia to enable timely
      management prior to their possible malignant transformation.

PMID- 24082732
TI  - Plasma total cholesterol level and some related factors in northern Iranian
      people.
AB  - BACKGROUND: In middle age people, hypercholesterolemia (HC) has been included as
      a risk factor for cardiovascular disease. OBJECTIVES: The main objective of this
      study was to evaluate the prevalence of HC and some related factors in the north
      of Iran. MATERIALS AND METHODS: This was a population-based cross-sectional study
      that enrolled 1995 subjects (997 males and 998 females) in 25-65 year age using
      stratified cluster sampling. Interviewers recorded the data using a
      multidimensional questionnaire including anthropometric indexes. Plasma
      cholesterol was measured in the morning after a 12-hour fast and determined by an
      auto-analyzer. HC was defined by a total plasma total cholesterol level over 200
      mg/dl. The SPSS.16 software was used to analyze data. RESULTS: The mean age of
      the participant was 44.2 years and mean +/- SD plasma total cholesterol level in
      men and women was 196.7 +/- 39.11 and 209.4 +/- 42.9, respectively. Generally,
      the prevalence of HC was 50.4% with a significant differences between men (44.7%)
      and women (57%) (P < 0.05). The mean plasma total cholesterol levels were
      significantly differenced among age groups, location area, BMI, and waist
      circumferences (P < 0.001). Women gender (OR = 1.64), 55-65 years old (OR =
      2.79), BMI >=40 kg/m(2) (OR = 10.0), and abdominal obesity (OR = 2.47) were
      associated with increased risk of HC (P = 0.001 and 95%CI for all). CONCLUSION:
      HC is one of the most health problems in the northern Iran and it is more common
      in women than in men. General and abdominal obesity are the most common risk
      factors for HC.

PMID- 24082733
TI  - Minor salivary glands and dental caries: Approach towards a new horizon.
AB  - INTRODUCTION: Reduction of functioning minor salivary glands may contribute to
      emergence of mucosal infections, mucosal ulceration, and possibly dental caries.
      A study was, therefore, designed to understand the exact role of minor salivary
      gland secretions over dental caries. METHODOLOGY: We studied the average labial
      distribution of functional minor salivary glands using various pre-defined
      locations, counted the minor salivary gland secretion imprints, and correlated
      the decayed missing filledlevels in subjects. The functional level and amount of
      secretion of minor salivary gland were evaluated. The radial immunodiffusion was
      performed by Diffu-Plate kit and the dimensions of the ring were correlated with
      the amount of immunoglobulin A in saliva. RESULTS: The mean number of functional
      labial minor salivary glands, amount of secretion, level of glycoprotein
      secretion, and immunoglobulin A secretion levels could very well dictate the
      functional status and role of minor salivary glands over caries assessment.
      CONCLUSION: The above-mentioned tests could be of major significance in routine
      diagnosis of the most common oral disease, i.e., dental caries.

PMID- 24082734
TI  - Relative fat distribution in relation to menarcheal status among Bengalee Hindu
      girls of West Bengal, India.
AB  - BACKGROUND: Menarche seems be related to the relative distribution rather than
      the total amount of body fat. Previous studies showed that the ratio between
      lower-body vs. upper-body fat was associated with the timing of menarche. AIM: To
      compare the relative distribution of subcutaneous fat among Bengali Hindu pre-
      and post-menarcheal girls. MATERIALS AND METHODS: The participants were 234
      Bengali Hindu girls aged 11-14 years: 111 pre-menarcheal and 123 post-menarcheal
      girls, randomly selected from a secondary school from a suburb of Kolkata, West
      Bengal, India. Triceps, abdominal, sub-scapular, and calf skinfolds were
      measured. For each skinfold site, ratio was calculated as follows: Log (one
      skinfold/sum of skinfolds). Principal components (PC) analysis was performed to
      derive components which express the maximum contrast among the log of ratios. T
      test was employed to assess differences between individual scores of components
      between pre- and post-menarcheal girls. RESULTS: The three identified PC
      suggested extremities-trunk, lower trunk-upper trunk, and an upper extremity
      lower extremity contrasts, respectively. Scores for second and third components
      showed significant differences between pre- and post-menarcheal groups of girls.
      CONCLUSION: The attainment of menarche by Bengali girls aged 11-14 years was
      associated with characteristically more relative subcutaneous fat distribution in
      the upper trunk and in the lower limbs, in contrast to lower trunk and upper
      limbs, respectively.

PMID- 24082735
TI  - Alterations in serum lipid profile patterns in oral cancer.
AB  - BACKGROUND: Alterations in serum lipids have long been associated with cancer as
      lipids play an important role in maintenance of cell integrity. AIMS: To evaluate
      alterations in plasma lipid profile in oral cancer patients, to compare and
      correlate the serum lipid profile in different grades of carcinoma and to
      evaluate the correlation of serum lipid profile between the tobacco habituates
      and non-habituates. MATERIALS AND METHODS: Among 75 study subjects, 50
      individuals were oral carcinoma patients and 25 individuals were healthy
      controls. The parameters assessed included total cholesterol (TC), high-density
      lipoprotein-cholesterol (HDLC), low-density lipoprotein-cholesterol, very low
      density lipoprotein-cholesterol and triglycerides (TGL). These groups were
      subdivided into subjects with no habit of tobacco (NHT) and subjects with habit
      of tobacco (WHT). STASTICAL ANALYSIS USED: Evaluation of results and statistical
      analysis was carried out using Student's t-test and one-way Analysis of Variance.
      RESULTS: There was a significant decrease in TC, HDLC and TGL in the oral cancer
      group as compared with the control group. The lipid profile levels between
      histological grading of the oral cancer and between WHT and NHT had no
      statistical significance. CONCLUSIONS: There was an inverse relationship between
      serum lipid profile and oral cancer. The lower serum lipid status may be
      considered a useful indicator for initial changes occurring in the neoplastic
      cells.

PMID- 24082736
TI  - The effect of periodontal treatment on C-reactive protein: A clinical study.
AB  - BACKGROUND: Chronic periodontitis in amultifactorial inflammatory disease which
      is caused by various microorganisms. Many studies have found close association
      between chronic periodontitis and C-reactive protein (CRP). CRPis an inflammatory
      marker which increases in all inflammatory condition. AIMS AND OBJECTIVE: The
      present clinical study was designed to show the effect of periodontal treatment
      on the CRP levels of gingival crevicular fluid and to determine the effect of
      nonsurgical therapy in minimizing the CRP levels in chronic generalized
      periodontitis. MATERIAL AND METHOD: Gingival crevicular fluid was collected using
      a micro capillary pipette that was hand calibrated at every 1 mm till 10 mm, from
      selected sites in the subjects on the 1st, 14th and 45th days. RESULTS AND
      CONCLUSION: Decreased CRP levels of gingival crevicular fluid were observed at
      the end of the study. There was a 37% reduction in probing pocket depth and 45%
      gain in clinical attachment level and a reduction of about 57% after 14 days and
      90% reduction of CRP levels in gingival crevicular fluid after 45 days. Thus, the
      results show that the presence of CRP level is more significant in gingival
      crevicular fluid and confirms the underlying inflammatory component of the
      disease activity in chronic periodontitis.

PMID- 24082737
TI  - Response of antioxidative enzymes to arsenic-induced phytotoxicity in leaves of a
      medicinal daisy, Wedelia chinensis Merrill.
AB  - BACKGROUND: Wedelia chinensis Merrill (Asteraceae) is a medicinally important
      herb, grown abundantly in soils contaminated with heavy metals, including toxic
      metalloid arsenic (As). The leaves have immense significance in treatment of
      various ailments. OBJECTIVE: The present study was undertaken to ascertain
      whether the edible/usable parts experience oxidative stress in the form of
      membrane damage during As exposure or not. MATERIALS AND METHODS: Responses of
      seven antioxidant enzymes were studied in leaves under 20 mg/L of As treatment in
      pot experiment. RESULTS: When compared to control, activities of superoxide
      dismutase, monodehydroascorbatereductase, dehydroascorbatereductase, glutathione
      reductase, and gluathione peroxidase had increased, while the catalase level
      reduced and ascorbate peroxidase activity changed non-significantly in As-treated
      seedlings. This suggested overall positive response of antioxidant enzymes to As
      induced oxidative stress. Although hydrogen peroxide content increased, level of
      lipid peroxidation and magnitude of membrane damage was quite normal, leading to
      normal growth (dry weight of shoot) of plant under Astreatment. CONCLUSION:
      W.chinensis is tolerant of As-toxicity, and thus, can be grown in As-contaminated
      zones.

PMID- 24082738
TI  - Suprapubic approach for laparoscopic appendectomy.
AB  - OBJECTIVE: To evaluate the results of laparoscopic appendectomy using two
      suprapubic port incisions placed below the pubic hair line. DESIGN: Prospective
      hospital based descriptive study. SETTINGS: Department of surgery of a tertiary
      care teaching hospital located in Rohtas district of Bihar. The study was carried
      out over a period of 11months during November 2011 to September 2012.
      PARTICIPANTS: Seventy five patients with a diagnosis of acute appendicitis.
      MATERIALS AND METHODS: All patients underwent laparoscopic appendectomy with
      three ports (one 10-mm umbilical for telescope and two 5 mm suprapubic as working
      ports) were included. Operative time, conversion, complications, hospital stay
      and cosmetic results were analyzed. RESULTS: Total number of patients was 75
      which included 46 (61.33%) females and 29 (38.67%) males with Mean age (+/
      Standard deviation {SD}) at the time of the diagnosis was 30.32 (+/-8.86) years.
      Mean operative time was 27.2 (+/-5.85) min. One (1.33%) patient required
      conversion to open appendectomy. No one patient developed wound infection or any
      other complication. Mean hospital stay was 22.34 (+/-12.18) h. Almost all
      patients satisfied with their cosmetic results. CONCLUSION: A laparoscopic
      approach using two supra pubic ports yields the better cosmetic results and also
      improves the surgeons working position during laparoscopic appendectomy.
      Although, this study had shown better cosmetic result and better working position
      of the surgeon, however it needs further comparative study and randomized
      controlled trial to confirm our findings.

PMID- 24082739
TI  - Evaluation of protective effect of N-acetyl cysteine on arsenic-induced
      hepatotoxicity.
AB  - OBJECTIVE: The present study was aimed to study protective role of N-acetyl
      cysteine (NAC) was assessed against arsenic (As)-induced hepatotoxicity in rats.
      METHODS: Twenty four male Wistar rats were divided into 4 groups of 6 animals
      each and treated as follows: Group 1: sham control, 2: arsenic control (sodium
      arsenite @ 10 mg/kg b. wt orally for 4 wks), 3: Pre-treatment with NAC (@ 300
      mg/kg orally for 2 wks) followed by sodium arsenite along with NAC (as per above
      doses) and 4: Sodium arsenite + NAC (as per above doses for 4 wks). RESULTS: The
      concentration of thiobarbituric acid reacting substances (TBARS) and protein
      carbonyls was significantly (P<0.05) increased, while the concentration of
      reduced glutathione (GSH), and the activity of CYP450, Na+ - K+ ATPase and Mg2+
      ATPase in liver were significantly (P<0.05) reduced in group 2 as compared to
      control. Groups 3 and 4 revealed improvement in the parameters in study.
      CONCLUSION: The study revealed that arsenic induces hepatotoxicity by inducing
      oxidative stress and supplementation of NAC is beneficial in countering the
      adverse effects.

PMID- 24082740
TI  - Comparative morpho-physiological and biochemical responses of lentil and grass
      pea genotypes under water stress.
AB  - BACKGROUND: Both lentil (Lens culinaris Medik.) and grass pea (Lathyrus sativus
      L.) in the family Fabaceae are two important cool-season food legumes, often
      experiencing water stress conditions during growth and maturity. OBJECTIVE: The
      present study was undertaken to ascertain the response of these two crops under
      different water stress regimes. MATERIALS AND METHODS: Different morpho
      physiological and biochemical parameters were studied in a pot experiment under
      controlled environmental conditions. Along with control (proper irrigation, 0
      stress), three sets of plants were subjected to mild (6 d), moderate (13 d) and
      severe (20 d) water stress by withholding irrigation at the appropriate time.
      RESULTS: Compared with control, plant growth traits and seed yield components
      reduced significantly in both crops with increasing period of water stress,
      resulting in lowering of dry mass with more severe effect on lentil compared with
      grass pea. Foliar Relative Water Content (RWC) (%), K(+)/Na(+) ratio, chlorophyll
      (chl) a, chl a/b ratio, stomatal conductance and net photosynthetic rate declined
      considerably in both crops under water stress. Leaf-free proline level increased
      significantly in both crops, but it decreased markedly in nodules of lentil and
      remained unchanged in grass pea. Nodulation was also affected due to water
      stress. The impairment in growth traits and physio-biochemical parameters under
      water stress was manifested in reduction of drought tolerance efficiency of both
      crops. CONCLUSION: Impact of water stress was more severe on lentil compared with
      grass pea, and modulation of growth traits signified necessity of a detailed
      strategy in breeding of food legumes under water stress.

PMID- 24082741
TI  - Comparative evaluation of microleakage of various retrograde filling materials:
      An in vitro study.
AB  - OBJECTIVE: The present study is envisaged to evaluate and compare the
      microleakage of mineral trioxide aggregate (MTA) with commonly used retrograde
      filling materials, like light-cured composite with dentin-bonding agents, light
      cured glass ionomer cement (LC GIC) and resin-modified zinc oxide eugenol.
      MATERIALS AND METHODS: Ninety freshly extracted non-carious single-rooted human
      anterior teeth were used in the study. They were randomly divided into four
      experimental groups and two control groups of 15 each. Following the
      biomechanical preparation, all teeth were obturated and then the apices of the
      obturated teeth were resected by removing 3 mm of each apex at 90 degrees  to the
      long axis of the tooth with a straight fissure bur in a high-speed air-rotor
      handpiece with water coolant. A 3-mm-deep root end cavity was prepared and the
      root end fillings were placed as per the manufacturer's instructions and
      according to the groups divided. The samples were then immersed in 1% methylene
      blue at room temperature for 72 h, 96 h and 1 week and the dye penetration was
      measured. RESULTS AND CONCLUSION: All the four materials used in the study showed
      some microleakage throughout the experimental period. The sealing ability in
      terms of microleakage can be summarized as: MTA > Composite resin with dentin
      bonding agent > LC GIC > Resin modified zinc oxide eugenol.

PMID- 24082742
TI  - Establishment of norms of the beta angle to assess the sagittal discrepancy for
      Nellore district population.
AB  - BACKGROUND AND OBJECTIVES: In orthodontic diagnosis and treatment planning,
      assessment of anteroposterior discrepancy is of importance to the orthodontist.
      Both angular and linear measurements have been incorporated into various
      cephalometric analyses to help the clinician diagnose anteroposterior
      discrepancies and establish the most appropriate treatment plan. Hence the
      present study is designed to establish the norms of Beta angle to assess the
      sagittal discrepancy for Nellore district population. MATERIALS AND METHODS: The
      sample was screened from the old records of the Orthodontic department of
      Narayana Dental College and Hospital. One hundred and fifty pretreatment
      cephalometric radiographs (50 each of Class I, II, and III) were subdivided based
      on ANB, Wits appraisal, and Beta angle into skeletal Class I, II, III. The same
      cephalograms were again classified into skeletal Class I, II, and III based
      purely on Beta angle. Each group was again divided into 2 subgroups consisting of
      25 male and 25 female subjects with a mean age limit between 15 and 45 years old.
      RESULTS: The Newman-keuls post hoc test and ANOVA showed that the 3 groups were
      significantly different (P <= 0.001). The Newman-keuls post hoc test also found
      the groups to be significantly different. CONCLUSIONS: There was statistically
      significant difference for, the mean values and the standard deviation for Beta
      angle within the three skeletal patterns (Class I, Class II and Class III
      skeletal patterns). There was no statistically significant difference among the
      mean values of beta angle between Nellore district population and Caucasian norms
      and between male and female sex groups.

PMID- 24082743
TI  - Protective role of N-Acetyl L-Cysteine against reproductive toxicity due to
      interaction of lead and cadmium in male Wistar rats.
AB  - INTRODUCTION: One of the target organs of heavy metals is testis and many authors
      proposed that oxidative stress could be responsible to induce their toxicity. An
      experimental study was conducted to evaluate the molecular mechanisms of lead
      (Pb) and cadmium (Cd) toxicity, their toxicodynamic interaction and to evaluate
      therapeutic potential of N-Acetyl L-cysteine (NAC) against the reproductive
      toxicity in male Wistar rats. MATERIAL AND METHODS: rats were randomly divided
      into 8 groups comprising of 6 rats in each. Group 1 and 2 were syam and NAC
      control, Group 3, 4 and 5 were kept as toxic control groups such as lead, cadmium
      and lead + cadmium respectively, where as Group 6, 7 and 8 were therapeutic
      groups with NAC. The experiment scheduled for 3 months. Body weights, anti
      oxidant profile (GSH, GST, TBARS and protein carbonyls) in testis, testis weight,
      testicular LDH, sperm count and histopathology were conducted. And also,
      interaction of Pb and Cd with zinc (Zn) and copper (Cu) in testis was assessed.
      RESULTS: The present study revealed significant alterations in body weights, anti
      oxidant profile, weights of testes, testicular LDH, sperm count, and
      concentration of Zn and Cu in toxic control groups 3, 4 and 5 as compared to
      control and NAC-treated groups. The toxic combination (Pb+Cd) group 5 showed
      significant alterations in protein carbonyls, GST levels and testicular LDH as
      compared to Pb and Cd alone administered groups and these results are
      substantiated with marked changes in the histopathology. All the NAC-treated
      groups revealed significant improvement in all the parameters. CONCLUSION: The
      results of the investigation revealed that Pb, Cd and their combination induces
      toxicity to the biological system due to the excess generation of free radicals
      and impairment of anti-oxidant defenses. Toxic effects were more pronounced in
      the group that received a combination of Pb and Cd, suggesting positive
      toxicodynamic interaction. Use of NAC countered the adverse effects of Pb and Cd
      induced toxicity to a major extent suggesting its anti-oxidant potential owing to
      replenishment of tissue pool of GSH. Further, NAC administration reduced the
      extent of accumulation of Pb and Cd in various tissues.

PMID- 24082744
TI  - Beneficial effect of aqueous root extract of Glycyrrhiza glabra on learning and
      memory using different behavioral models: An experimental study.
AB  - BACKGROUND: In the traditional system of medicine, the roots and rhizomes of
      Glycyrrhiza glabra (Gg) (family: Leguminosae) have been studied for their ability
      to improve a variety of health ailments. AIMS: The present study was designed to
      investigate the beneficial effects of Gg root extract on learning and memory in 1
      month-old male Wistar albino rats. Four doses (75, 150, 225, and 300 mg/kg) of
      aqueous extract of root of Gg was administered orally for six successive weeks.
      MATERIALS AND METHODS: The aqueous extracts were evaluated for their effect on
      spatial learning and memory in rats using the elevated plus maze, Hebb-William
      maze, and Morris water maze tests which served as the exteroceptive behavioral
      model. Diazepam-induced amnesia served as the interoceptive behavioral model.
      RESULTS: Results showed that all the doses of aqueous root extract of Gg
      significantly enhanced the memory; however, in the doses of 150 and 225 mg/kg, it
      showed a significant (P < 0.01) enhancement in learning and memory. Furthermore,
      Diazepam-induced amnesia was reversed by the aqueous root extract of Gg (150 and
      225 mg/kg, p.o.). CONCLUSION: These findings suggest that the memory enhancement
      effects of Gg may be mediated by its antioxidant and anti-inflammatory
      activities. Thus, Gg appears to be a promising drug for improving memory in the
      management of impaired learning, dementia, Alzheimer's disease, and other
      neurodegenerative disorders.

PMID- 24082745
TI  - Median mandibular flexure at different mouth opening and its relation to
      different facial types: A prospective clinical study.
AB  - OBJECTIVE: To measure the arch width and Median mandibular flexure (MMF) values
      at relative rest and maximum jaw opening in young adults with Dolichofacial,
      Mesofacial, and Brachyfacial types and tested whether the variation in the facial
      pattern is related to the MMF values in South Indian population. MATERIALS AND
      METHODS: This Prospective clinical study consisted of sample of 60 young adults.
      The subjects were grouped into 3 groups: Group 1: Brachyfacial, Group 2:
      Mesofacial and types, Group 3: Dolichofacial. Impressions were taken for all the
      60 subjects and the casts were scanned and digitized. The intermolar width was
      measured for Dolichofacial, Mesofacial, and Brachyfacial subjects at relative
      rest (R) and maximum opening (O). RESULTS: The statistical analysis of the
      observations included Descriptive and Inferential statistics. The statistical
      analysis was executed by means of Sigma graph pad prism software, USA Version-4.
      Kruskal wallis (ANOVA) followed by Dunns post hoc test was performed. Mann
      Whitney U-test was performed to assess the difference in MMF values between Males
      and Females of the three groups. The Mean (SD) Mandibular flexure in individuals
      with Brachyfacial type was 1.12 (0.09), Mesofacial type was 0.69 (0.21), and
      Dolichofacial type was 0.39 (0.08). CONCLUSIONS: The Mean intermolar width was
      maximum in Brachyfacial type and minimum in Dolichofacial type. MMF was maximum
      at the maximum mouth opening position and was maximum in individuals with
      Brachyfacial type.

PMID- 24082746
TI  - Diversity of endophytic bacteria in medicinally important Nepenthes species.
AB  - BACKGROUND: Nepenthes species are used in traditional medicines to treat various
      health ailments. However, we do not know which types of endophytic bacteria (EB)
      are associated with Nepenthes spp. OBJECTIVE: The objective of this study was to
      isolate and to identify EB associated with Nepenthes spp. MATERIALS AND METHODS:
      Surface-sterilized leaf and stem tissues from nine Nepenthes spp. collected from
      Peninsular Malaysia were used to isolate EB. Isolates were identified using the
      polymerase chain reaction-amplified 16S ribosomal DNA (rDNA) sequence similarity
      based method. RESULTS: Cultivable, 96 isolates were analyzed; and the 16S rDNA
      sequences analysis suggest that diverse bacterial species are associated with
      Nepenthes spp. Majority (55.2%) of the isolates were from Bacillus genus, and
      Bacillus cereus was the most dominant (14.6%) among isolates. CONCLUSION:
      Nepenthes spp. do harbor a wide array of cultivable endophytic bacteria.

PMID- 24082747
TI  - Liquid chromatographic determinations of meta-chlorobenzoic acid in bupropion
      hydrochloride.
AB  - A simple, sensitive method for the determination of meta-chlorobenzoic acid in
      bupropion hydrochloride is described. Chromatographic separation of m
      chlorobenzoic acid is achieved using a mobile phase consisting of n-hexane and
      ethanol (1000:50, v/v) at a flow rate of 1.0 ml/min on a Chiralpak ADH (250 * 4.6
      mm). Absorbance is monitored at 235 nm. The method is linear for m-chlorobenzoic
      acid over concentration range of LOQ, 5.0 MUg/ml to 15.0 MUg/ml for m
      chlorobenzoic acid with correlation coefficient greater than 0.99. This method is
      more selective and accurate than United States Pharmacopoeia method for the
      determination of m-chlorobenzoic acid in bupropion hydrochloride. 

PMID- 24082748
TI  - Smoking re-initiation after cessation program: Comparison of associated factors
      between young and older adults.
AB  - OBJECTIVE: To evaluate the associated factors in reinitiating the smoking habit
      among the participants of a smoking cessation program conducted in a tobacco
      cessation clinic of Manipal University, Manipal. MATERIALS AND METHODS: This
      cross-sectional study was conducted among participants of a smoking cessation
      program who reinitiated smoking habit. A self-administered questionnaire was used
      that had information on demographic, habit history, knowledge on harmful effects
      of smoking behavior related to oral cavity and associated factors due to which
      individual was unable to quit the habit. RESULTS: A total of 102 males (mean age
      = 39.91 +/- 9.57) constituted the final sample. The results showed that habitual
      smokers were more likely to be >=40 years and occasional smokers were all
      reported to be <93 years (P < 0.001). Cigarette smokers were more likely to be of
      younger age group while majority of the Beedi and cigarette + Beedi smokers were
      older adults (P < 0.001). The mean duration of the habit was significantly higher
      for older adults than young adults (P < 0.001). There was no significant
      difference in the number of packs between the age groups (P = 0.054). A
      significantly higher proportion of young adults than older adults were aware
      about oral cancer (P < 0.001). Significantly higher proportion of older adults
      than young adults tend to have a closest person to be a smoker (P = 0.05). A
      significant higher proportion of young adults reason their habit as for pleasure
      (84.6%) and relaxation (68.8%), while older adults reason it to be as tension
      (64.1%) or combined factors (70.6%). Peer pressure was almost same in both the
      age groups (P = 0.006). There were no significant differences in the withdrawal
      symptoms among young and older adults (P = 0.41). CONCLUSION: Considerable
      differences were noticed between younger and older age groups in the factors
      which might play a role in re-intiating the smoking habit. A structured cessation
      program focused more on the above characteristics should be planned in public
      health programs based on the characteristics of the participants.

PMID- 24082749
TI  - Hereditary ectodermal dysplasia: A retrospective study.
AB  - BACKGROUND: Ectodermal dysplasia (ED) is a group of rare, inherited disorders
      characterized by sparse hair, missing teeth and inability to sweat. OBJECTIVE: To
      review and analyze cases of ED with an emphasis on clinical manifestations and
      parent's marriage history. METHODOLOGY: The present retrospective study was
      conducted by assessing the clinical records of nineteen cases of ED, available in
      the archives of the department; for age, gender, family history of consanguineous
      marriage and clinical manifestations. RESULTS: It was observed that ED was more
      prevalent in males, with a ratio of 1.7:1. The hypohydrotic type was more common
      (78.95%) than hydrotic type (21.05%). The marriage history of parents revealed
      that 66.67% had consanguineous marriage and had 68.42% offspring's affected with
      ED; whereas 33.33% had history of non-consanguineous marriage and had 31.58%
      offspring's affected with ED. The clinical manifestations observed were- dry
      skin(94.74%); scaly skin(42.11%); sparse hair on scalp, eyebrows and
      eyelashes(100%); frontal bossing(63.18%); saddle nose (57.89%); hypertelorism
      (47.37%); nail abnormality(52.63%); normal sweat glands(21.05%); abnormal sweat
      glands(78.95%); hypoplastic maxilla(52.63%); protuberant lips (57.89%); palmo
      plantar keratosis(21.05%); wrinkled & hyper pigmented facial skin(84.21%);
      partial anodontia(94.74%); conical shaped teeth(84.21%); high arched
      palate(68.42%); thin alveolar bone(100.00%); taurodontism(21.05%) and cleft lip &
      cleft palate(05.26%). The number of teeth present in all the cases ranged from 0
      to 19. CONCLUSION: ED patients suffer from social problems and poor psychological
      and physiological development as a result of unacceptable esthetics and abnormal
      function of orofacial structures. Oral rehabilitation thus becomes mandatory,
      although it is often difficult; particularly in pediatric patients.

PMID- 24082750
TI  - Dental health status and treatment needs of transport workers of a northern
      Indian city: A cross-sectional study.
AB  - AIM: To assess the dental health status and treatment needs of transport workers
      working in Chandigarh Transport Undertaking (C.T.U.) buses, Chandigarh. MATERIALS
      AND METHODS: A cross-sectional study was conducted on all the available C.T.U.
      workers at all three bus depots. The data were recorded on a modified W.H.O.
      format (1997). A total of 1008 subjects constituted the final sample size.
      RESULTS: The mean age of the subjects was 45.3 +/- 7.8 years, and 97% (978) were
      males. Prevalence of dental caries was 63.4% and mean DMFT was 5.02. 47.6% of
      subjects needed some prosthesis in the maxillary arch while 53.3% needed some
      prosthesis in the mandibular arch. Regarding highest CPI (Community Periodontal
      Index) score, 8.13% of the subjects had healthy periodontium while maximum
      subjects (73.2%) had a score 2 (Calculus). CONCLUSION: Mean DMFT (Decayed,
      Missing and Filled Teeth) was satisfactory. Prosthetic need of the subjects was
      high with only a few subjects possessing prosthesis. Advanced periodontal disease
      (CPI score, 4) affected small number of subjects with maximum subjects (73%)
      having a CPI score of 2.

PMID- 24082751
TI  - Mandibular adenomatoid odontogenic tumor: Radiographic and pathologic
      correlation.
AB  - Adenomatoid odontogenic tumor (AOT) is a rare tumor of epithelial origin
      comprising 3% of all the odontogenic tumors. It is a benign, painless,
      noninvasive, and slow-growing lesion, with a relative frequency of 2.2-13% and
      often misdiagnosed as an odontogenic cyst on clinical examination. AOT affects
      young individuals with a female predominance, occurs mainly in the second decade,
      and usually surrounds the crown of unerupted teeth. This lesion is most commonly
      located in the anterior maxilla and rarely in the mandible. It is usually
      associated with an impacted canine. AOT frequently resembles lesions like
      dentigerous cyst or ameloblastoma. AOT has three variants, follicular,
      extrafollicular, and peripheral. The intraoral periapical radiograph is the best
      radiograph to show radiopacities in AOT as discrete foci having a flocculent
      pattern within radiolucency even with minimal calcified deposits. These calcified
      deposits are seen in approximately 78% of the lesions. Herewith, we present the
      report of four unusual cases of AOT located in the mandible, with an emphasis on
      radiographic findings and on pathologic correlation, and on reviewing the
      existing literature on this tumor. 

PMID- 24082752
TI  - Amelogenesis imperfecta: Four case reports.
AB  - Amelogenesis Imperfecta (AI) represents a group of developmental conditions,
      genomic in origin, which affect the structure and clinical appearance of enamel
      of all or nearly all the teeth in a more or less equal manner. AI is a serious
      problem that reduces oral health-related quality of life and causes some
      physiological problems. We presented here four case reports of AI (Hypoplastic
      and Hypomaturation) which we diagnosed on the basis of classical clinical and
      radiographic features. 

PMID- 24082753
TI  - Osteochondroma of mandibular condyle: A clinic-radiographic correlation.
AB  - Osteochondroma (OC) of temporo mandibular joint is a rare, slow growing, benign
      tumor that causes a progressive enlargement of the condyle, usually resulting in
      facial asymmetry, temporo mandibular joint (TMJ) dysfunction, limited mouth
      opening and malocclusion. Pain is rarely associated with this tumor. OC is
      composed of cartilaginous and osseous tissues. Radiographically, there is
      unilaterally enlarged condyle usually with an exophytic outgrowth of the tumor
      from the condylar head. We present a rare case of osteochondroma of right
      mandibular condyle in a 45-year-old male who reported with painless swelling over
      TMJ area and progressive limited mouth opening. Panoramic radiograph and computed
      tomography (CT) was performed for better evaluation of the pathological
      condition. This paper describes the clinico-radiographic features and
      differential diagnosis of OC. 

PMID- 24082754
TI  - An innovative metal base denture design for a 55-year-old menopausal woman.
AB  - Menopause is a normal developmental stage in a woman's life, marking the
      permanent cessation of menstruation resulting from irreversible changes in the
      hormonal and reproductive functions of the ovaries and is associated with a large
      number of symptoms ranging from physical to psychological. Some of the common
      oral manifestations are oral burning sensation with associated mucosal
      infections, pain, altered taste perception, and alveolar bone loss. These
      symptoms may unfavorably affect oral health and treatment needs requiring
      dentists to devise newer methods that would add along to the treatment modalities
      advised by gynecologists in relieving menopausal women from above symptoms. The
      present case report describes an innovative method of fabricating a metal base
      denture in an edentulous female that would help perimenopausal/menopausal/post
      menopausal edentulous women feel hot/cold sensations of food/liquids, thereby
      giving them relief from pain, better taste perception, and relief from associated
      allergic and candidal infections that are common with conventional acrylic base
      dentures. 

PMID- 24082755
TI  - A 25-year-old man with 50 teeth: Astonishing but true!!
AB  - Retained primary teeth is a well-known process but multiple retained primary,
      permanent, and supernumerary teeth that too in an asymptomatic, non-syndromic
      patient is a rare possibility that has rarely been reported in literature. This
      case report discusses the clinical and radiographic details along with treatment
      options in a 21-year-old patient having a total number of 50 teeth, i.e., 16
      retained primary teeth, 32 permanent teeth, and 2 supernumerary teeth without
      being associated with any known syndrome complex or metabolic disorder. 

PMID- 24082756
TI  - Juvenile osteoporosis in a 5-year-old girl.
AB  - Idiopathic juvenile osteoporosis (IJO) is a term used to describe a primary
      osteoporosis of unknown etiology in prepubertal children. It is rarely described
      in the literature and treatment modalities vary with spontaneous remission also
      being reported at the time of puberty. We report a 5-year-old girl with IJO who
      had spinal deformities and was successfully treated with oral alendronate. 

PMID- 24082757
TI  - Cutaneous histoplasmosis in a HIV seronegative patient.
AB  - A patient presented with multiple nodulo-ulcerative lesions over neck and chest.
      Lymphadenopathy and systemic involvement were absent. Patient was seronegative
      for HIV. There was no history of local injury and no history of travel.
      Histopathological findings were consistent with histoplasmosis. Diagnosis of
      primary cutaneous histoplasmosis was made. We highlight this case owing to its
      rare and atypical presentation, in an attempt to promote clinical and micro
      pathological awareness regarding such occurrences. 

PMID- 24082758
TI  - Elbow dislocation with ipsilateral distal radius fracture.
AB  - Elbow dislocation associated with ipsilateral distal radius fracture is a rare
      pattern of injury, although it is common for elbow dislocation and forearm
      fractures to occur separately. We report a rare case of a 20-year-old male who
      had a posterior elbow dislocation and ipsilateral distal radius fracture. Elbow
      dislocation was first reduced in extension and distal radius fracture was then
      reduced in flexion. Both the injuries were conservatively managed. At 6 months
      follow-up, the patient had no pain in his elbow and minimal pain in his wrist on
      heavy lifting and had resumed his work as a laborer. 

PMID- 24082759
TI  - Uncoiling of reamer during intramedullary nailing for fracture shaft of femur.
AB  - Intramedullary nailing is considered the standard of care for closed femoral
      shaft fractures. Several studies have shown that reamed intramedullary nailing is
      a safe procedure in fracture shaft femur with lower nonunion rates than unreamed
      nailing. Reamed intramedullary nailing provides better stability because of
      increased contact between the nail and medullary canal. However, careful
      attention to reaming techniques as well good instrumentation is necessary while
      undertaking such a procedure. We report what is, to the best of our knowledge,
      the first case of uncoiling of reamer while reaming the medullary canal. Possible
      causes and measures to avoid such a complication are discussed. 

PMID- 24082760
TI  - Infiltrative odontogenic myxoma of the posterior maxilla: Report of a case.
AB  - Myxomas of the head and neck are rare tumors of uncertain histogenesis.
      Odontogenic myxomas in maxilla are less common but behave more aggressively, as
      it spreads through maxillary antrum. It therefore reaches considerable size
      before being detected. The current case arouses particular interest due to the
      rapid growth and infiltrating nature of the lesion in a 25-year-old female
      patient, who denied any leading symptoms, even with the lesion involving
      extensively. Radiographic and microscopic similarities to a number of entities
      make diagnostic interpretation of odontogenic myxoma challenging. Therefore sound
      knowledge of clinical, radiographic and histopathologic features is important to
      establish an appropriate treatment aimed at a good clinical course and patient
      cure. 

PMID- 24082761
TI  - Schwannoma of floor of the mouth.
AB  - Schwannoma is an intraoral rare, benign neoplasm arising from and consisting
      solely of Schwann cells. Its etiology is unknown. It presents as a solitary, slow
      growing, smooth surfaced, generally asymptomatic firm mass. Schwannomas commonly
      occur between 30 and 50 years. It is relatively uncommon, although a quarter of
      all Schwannoma's occurs in the head and neck region. Schwannoma of the floor of
      the mouth is rare in the oral region. Described is a case of Schwannoma of the
      floor of the mouth in a 28-year-old male, of large size. 

PMID- 24082762
TI  - A rare case of Kikuchi-Fujimoto disease.
AB  - Kikuchi-Fujimoto disease, characterized by histiocytic necrotizing lymphadenitis,
      closely mimics tuberculosis, and lymphoma are two most common etiologies of
      cervical lymphadenitis. It is a rare, benign, and self-limited disease. Viral
      infections or autoimmunity are hypothesized as its etiology, but no causal
      relationship is definitely established till date. No specific treatment is
      available, only supportive treatment is given. Here, we represent a rare case of
      Kikuchi's disease in a 29-year-old male patient who presented to us with right
      sided posterior cervical lymphadenopathy with low-grade fever for three months. 

PMID- 24082763
TI  - Adenolymphoma: A probing entity: Case report and review.
AB  - Warthin's tumor undoubtedly is the most frequent monomorphic adenoma of the major
      salivary glands. Clinically, it appears as a slow-growing tumor often fluctuant
      on palpation due to its cystic nature. The treatment of choice is complete
      excision with wide tumor-free margins. This article highlights a case of
      Warthin's tumor of the parotid gland in an elderly male patient along with a
      review of the literature on the aforementioned pathology. 

PMID- 24082764
TI  - Primary choriocarcinoma metastasizing to skeletal muscles, presenting as an
      abdominal wall mass: A rare presentation.
AB  - Choriocarcinoma is a highly malignant tumor of the trophoblastic origin. Most
      cases are present within 1 year of antecedent pregnancy. We present an extremely
      rare case of choriocarcinoma of the anterior abdominal muscle in a 41-year-old
      female who presented as mass in anterior abdominal wall 4 months after undergoing
      a total abdominal hysterectomy with bilateral salpingo oophorectomy for a
      diagnosis of fibroid uterus. Laparotomy done for the mass revealed it to be an
      extraperitoneal mass within the rectus muscle that on histopathological
      examination was confirmed to be primary choriocarcinoma. Computed tomography scan
      revealed pulmonary metastases and patient was given combination chemotherapy to
      which she responded well. 

PMID- 24082765
TI  - Bilateral anterior shoulder dislocation.
AB  - Shoulder dislocations are the most common major joint dislocations encountered in
      the emergency departments. Bilateral shoulder dislocations are rare and of these,
      bilateral posterior shoulder dislocations are more prevalent than bilateral
      anterior shoulder dislocations. Bilateral anterior shoulder dislocation is very
      rare. We present a case of 24-year-old male who sustained bilateral anterior
      shoulder dislocation following minor trauma, with associated greater tuberosity
      fracture on one side. Prompt closed reduction followed by immobilization in arm
      sling and subsequent rehabilitation ensured a good outcome. 

PMID- 24082766
TI  - Ochronotic black meniscus during knee arthroscopy.
AB  - Ochronotic arthropathy is a rare condition found in patients with alkaptonuria,
      which is a hereditary metabolic disease associated with deposition the of
      homogentisic acid derivatives in various connective tissues of the body. We
      present the case of a 30-year-old woman in whom arthroscopic examination of the
      left knee prior to meniscectomy for bucket handle tear of medial meniscus
      revealed brown-black discoloration of the articular cartilage and menisci leading
      to the diagnosis of alkaptonuria by further laboratory evaluation. After medical
      and surgical treatment, patient's complaints were alleviated and no further
      complaints were registered, during the next follow-up. 

PMID- 24082767
TI  - Ptosis repair using preserved fascia lata with the modified direct tarsal
      fixation technique.
AB  - PURPOSE: To evaluate the clinical outcome of frontalis sling operation using
      preserved fascia lata with modified direct tarsal fixation in congenital ptosis
      patients. METHODS: Forty-seven congenital ptosis patients (60 eyes) who underwent
      a frontalis sling operation using preserved fascia lata with modified direct
      tarsal fixation method between March 2001 and December 2008 with a mean follow-up
      time of 52 months (range, 26 to 122 months) were included in this study. The
      medical records were reviewed retrospectively. RESULTS: A retrospective chart
      review was conducted in patients who were diagnosed with congenital ptosis and
      underwent frontalis suspension surgery using preserved fascia lata with modified
      direct tarsal fixation from 2001 through 2008 at Dong-A University Hospital. The
      patients were 34 males and 14 females. The age of the patients ranged from 1 to
      18 years with an average age of 4.51 years. At a mean follow-up of 60 months,
      good final results were achieved in 46 eyes (76.6%), fair in 8 eyes (13.3%), and
      poor in 6 eyes (10%). The poor results consisted of undercorrection of 1 eye and
      recurrence in 5 eyes. The accumulative survival rate was 87.2%, with all
      recurrences occurring within 12 months postoperatively. CONCLUSIONS: Frontalis
      sling operation by preserved fascia lata with modified direct tarsal fixation
      appears to be an effective treatment for severe congenital ptosis, showing good
      long term results.

PMID- 24082768
TI  - Comparative analysis of polymerase chain reaction assay for herpes simplex virus
      1 detection in tear.
AB  - PURPOSE: To comparatively analyze the methodological efficacy of the polymerase
      chain reaction (PCR) assay for herpes simplex virus 1 (HSV) detection in tears.
      METHODS: This retrospective study reviewed the medical records of 115 patients
      who were clinically diagnosed with herpes keratitis, and their tear samples were
      collected for HSV detection. PCR positive rates were analyzed for their
      dependence on the PCR primers used (conventional PCR primer vs. nested PCR
      primer), the tear collecting method used (micropipetting vs. collection with
      schirmer strip), the disease manifestation and the patient's previous medication
      history. RESULTS: HSV DNA was detected in 23 out of 115 (20%) tear samples. The
      PCR positive rate in tear samples did not differ depending on the PCR primer or
      tear collection method used. Typical epithelial lesions showed a higher positive
      rate (31.4%) than atypical epithelial lesions (10.9%). The previous history of
      the antiviral agent seemed to affect the PCR positive rate. CONCLUSIONS: Although
      the PCR positive rate was not dependent on the tear collection method or primers,
      HSV detection in tears using PCR was shown to be a supplementary diagnostic test
      in typical and atypical herpes epithelitis.

PMID- 24082769
TI  - Comparison of clinical outcomes of same-size grafting between deep anterior
      lamellar keratoplasty and penetrating keratoplasty for keratoconus.
AB  - PURPOSE: To compare the clinical outcomes between deep anterior lamellar
      keratoplasty (DALK) and penetrating keratoplasty (PKP) with same-size grafts in
      patients with keratoconus. METHODS: Medical records of 16 eyes from 15 patients
      treated from June 2005 through April 2011 were retrospectively reviewed. Patients
      with contact lens intolerance or who were poor candidates for contact lens
      fitting due to advanced cone underwent keratoplasty. The transplantations
      consisted of 11 DALK and 5 PKP with same-size grafting for keratoconus. Best
      corrected visual acuity (BCVA), refractive error, corneal topographic profiling,
      and clinical course were compared between DALK and PKP groups. RESULTS: The
      follow-up period was 30 +/- 17 months in the DALK group and 45 +/- 20 months in
      the PKP group (p = 0.145). At final follow-up, the DALK and PKP groups achieved a
      BCVA (logarithm of the minimum angle of resolution) of 0.34 and 0.52,
      respectively (p = 0.980). Postoperative refractive error and mean simulated
      keratometric index showed myopic astigmatism in both groups without any
      statistical difference. Corneal irregularity index measured at 5 mm in the DALK
      group was less than that of the PKP group at 1-year follow-up (p = 0.021);
      however, at final follow-up, there was no longer a statistically significant
      difference. Endothelial cell counts were lower in the PKP group than in the DALK
      group at final follow-up (p = 0.021). CONCLUSIONS: The optical outcomes of DALK
      with same-size grafts for keratoconus are comparable to those of PKP. Endothelial
      cell counts are more stable in DALK compared to PKP.

PMID- 24082770
TI  - Effect of age and early intervention with a systemic steroid, intravenous
      immunoglobulin or amniotic membrane transplantation on the ocular outcomes of
      patients with Stevens-Johnson syndrome.
AB  - PURPOSE: This retrospective observational case series of fifty-one consecutive
      patients referred to the eye clinic with acute-stage Stevens-Johnson syndrome
      (SJS) or toxic epidermal necrolysis (TEN) from 1995 to 2011 examines the effect
      of early treatment with a systemic corticosteroid or intravenous immunoglobulin
      (IVIG) on the ocular outcomes in patients with SJS or TEN. METHODS: All patients
      were classified by age (<=18 years vs. >18 years) and analyzed by treatment
      modality and early intervention with systemic corticosteroids (<=5 days), IVIG
      (<=6 days), or amniotic membrane graft transplantation (AMT) (<=15 days). The
      main outcomes were best-corrected visual acuity (BCVA) in logarithm of the
      minimum angle of resolution (logMAR) and ocular involvement scores (OIS, 0-12),
      which were calculated based on the presence of superficial punctate keratitis,
      epithelial defect, conjunctivalization, neovascularization, corneal opacity,
      keratinization, hyperemia, symblepharon, trichiasis, mucocutaneous junction
      involvement, meibomian gland involvement, and punctal damage. RESULTS: The mean
      logMAR and OIS scores at the initial visit were not significantly different in
      the pediatric group (logMAR = 0.44, OIS = 2.76, n = 17) or the adult group
      (logMAR = 0.60, OIS = 2.21, n = 34). At the final follow-up, the logMAR and OIS
      had improved significantly in the adult group (p = 0.0002, p = 0.023,
      respectively), but not in the pediatric group. Early intervention with IVIG or
      corticosteroids significantly improved the mean BCVA and OIS in the adult group
      (p = 0.043 and p = 0.024, respectively for IVIG; p = 0.002 and p = 0.034,
      respectively for corticosteroid). AMT was found to be associated with a
      significantly improved BCVA or OIS in the late treatment group or the group with
      a better initial OIS (p = 0.043 and p = 0.043, respectively for BCVA; p = 0.042
      and p = 0.041, respectively for OIS). CONCLUSIONS: Our findings suggest that
      patients with SJS or TEN who are aged 18 years or less have poorer ocular
      outcomes than older patients and that early treatment with steroid or
      immunoglobulin therapy improves ocular outcomes.

PMID- 24082771
TI  - External ophthalmomyiasis presenting to an emergency department: corneal findings
      as a sign of Oestrus ovis.
AB  - PURPOSE: This study aims to determine the frequency of opthalmyomyiasis externa
      and the ocular findings of disease in Southern Khorasan. METHODS: All patients
      referred to the emergency department of Valiaser hospital during the year 2011
      with external ophthalmomyiasis were enrolled in this study. The diagnosis of
      external ophthalmomyiasis was made according to clinical findings and the
      presence of Oestrus ovis larvae. RESULTS: There were 18 cases of external
      ophthalmomyiasis in the emergency department of Valiaser hospital in 2011. Most
      cases had the common signs and symptoms of allergic conjunctivitis, except for
      three males who were referred with respective complaints of red eye, foreign body
      sensation, and swelling around the eyelids after contact injury the previous day;
      corneal infiltration was present in three cases. The visual acuity among the
      three cases that had peripheral corneal involvement was 20 / 30 in both eyes. The
      bulbar conjunctiva showed chemosis in all cases and a ropy pattern discharge that
      was clinically compatible with external ophthalmomyiasis. However, in one case,
      microscopic slit lamp examination did not show Oestrus ovis larvae. CONCLUSIONS:
      The frequency of external ophthalmomyiasis was high in this region. Although
      external ophthalmomyiasis usually manifests as allergic conjunctivitis, coronary
      like corneal infiltration may be considered in the differential diagnosis of
      external ophthalmomyiasis or toxic insult.

PMID- 24082772
TI  - Cataracts among adults aged 30 to 49 years: a 10-year study from 1995 to 2004 in
      Korea.
AB  - PURPOSE: To investigate the long-term characteristics of cataracts among adults
      aged 30 to 49 years in Korean over a span of 10 years. METHODS: Subjects between
      the ages of 30 to 49 years who underwent cataract surgery at St. Mary's Hospital
      from 1995 to 2004 (n = 976) were included. Patients with a history of ocular
      trauma, uveitis, other ocular or systemic diseases, and congenital cataracts were
      excluded. Additional information including type of lens opacity, urban/rural
      region, and pre- and postoperative visual acuities were analyzed. Lens opacity
      grading was conducted using Lens Opacity Classification System III. The Cochran
      Armitage proportion trend test was used to analyze vision changes with the
      passage of time. RESULTS: Among the patients who had undergone cataract
      surgeries, 8.8% (976 / 11,111) met the inclusion criteria. The mean age was 41.7
      +/- 5.45 years. Gender breakdown of the patient population included 79.0% male
      and 21.0% female. In terms of home environment, 60.9% were from an urban region
      and 39.1% from a rural region. Opacity type included anterior polar (AP),
      posterior subcapsular (PSC), AP and PSC, cortical, and nuclear in 35.7%, 35.1%,
      7.0%, 6.0%, and 5.4% of patients, respectively. At a 2-month postoperative follow
      up appointment, 92.7% of patients showed a best-corrected visual acuity of more
      than 20 / 40. CONCLUSIONS: Predominance of AP and PSC opacities as well as male
      patients was observed in this study population.

PMID- 24082773
TI  - Characteristic findings of optical coherence tomography in retinal angiomatous
      proliferation.
AB  - PURPOSE: To identify the unique pathologic findings of retinal angiomatous
      proliferation (RAP) in optical coherence tomography (OCT). METHODS:
      Retrospectively, 29 eyes of 25 patients with age-related macular degeneration and
      complicated RAP were analyzed. All 29 eyes had choroidal neovascularization (CNV)
      in the area of pigment epithelial detachment (PED) or adjacent to it, which was
      visible with fluorescein angiography or indocyanine green angiography. Cross
      sectional images were obtained by OCT scanning through the CNV lesions. RESULTS:
      Six distinctive findings of OCT included drusen (100%), inner retinal cyst (80%),
      outer retinal cyst (68%), fibrovascular PED (84%), serous retinal detachment
      (40%), and PED (68%). CONCLUSIONS: Through analysis of OCT findings, we revealed
      six different types of lesions distinctive of RAP which may provide helpful
      diagnostic information for subsequent treatment and predicting the prognosis of
      RAP.

PMID- 24082774
TI  - Comparison of the outcome of silicone Ahmed glaucoma valve implantation with a
      surface area between 96 and 184 mm2 in adult eyes.
AB  - PURPOSE: To compare the success rates, complications, and visual outcomes between
      silicone Ahmed glaucoma valve (AGV) implantation with 96 mm(2) (FP8) or 184 mm(2)
      (FP7) surface areas. METHODS: This study is a retrospective review of the records
      from 132 adult patients (134 eyes) that underwent silicone AGV implant surgery.
      Among them, the outcomes of 24 eyes from 24 patients with refractory glaucoma who
      underwent FP8 AGV implantation were compared with 76 eyes from 76 patients who
      underwent FP7 AGV implantation. Preoperative and postoperative data, including
      intraocular pressure (IOP), visual acuity, number of medications, and
      complications were compared between the 2 groups. RESULTS: There were no
      significant differences in baseline characteristics between the 2 groups (p >
      0.05). The postoperative visual acuity of the patients in the FP8 group was
      better than that of the patients in the FP7 group in some early postoperative
      periods (p < 0.05); however, after 10 postoperative months, visual acuity was not
      significantly different through the 3-year follow-up period (p > 0.05).
      Postoperative IOP was not significantly different between the 2 groups (p > 0.05)
      except for IOP on postoperative day 1 (11.42 mmHg for the FP7 group and 7.42 mmHg
      for the FP8 group; p = 0.031). There was no statistical difference in success
      rates, final IOP, number of medications, or complication rates between the 2
      groups (p > 0.05). CONCLUSIONS: The FP7 and FP8 AGV implants showed no difference
      in terms of vision preservation, IOP reduction, and number of glaucoma
      medications required.

PMID- 24082775
TI  - Human papilloma virus in retinoblastoma tissues from Korean patients.
AB  - PURPOSE: Recent reports suggest the association of human papilloma virus (HPV)
      with retinoblastoma. This study was performed to elucidate whether HPV infection
      is related to retinoblastoma among Koreans. METHODS: A total of 54 cases
      diagnosed with retinoblastoma were enrolled from Seoul National University
      Children's Hospital and Seoul Metropolitan Government-Seoul National University
      Boramae Medical Center. Presence of human papilloma viral DNA was detected by in
      situ hybridization in formalin-fixed paraffin-embedded retinoblastoma tissues
      using both probes against high- and low risk HPV types. RESULTS: The mean age at
      diagnosis was 22.0 months (range, 1.1 to 98.0 months), and the mean age at
      enucleation was 27.8 months (range, 1.5 to 112.7 months) among the 54 patients
      with retinoblastoma. HPV was not detected in any of the retinoblastoma samples
      using either high risk or low risk HPV probes. CONCLUSIONS: Our study, being the
      first study in the Korean population, proposes that HPV infection may have no
      causal relationship with retinoblastoma in Koreans.

PMID- 24082776
TI  - Acute bilateral visual loss related to orthostatic hypotension.
AB  - A 50-year-old man had undergone lumbar vertebral surgery and was confined to bed
      in the supine position for three months. When he sat up from the prolonged supine
      position, he showed clinical signs of orthostatic hypotension and reported
      decreased vision in both eyes. He also had underlying anemia. Ophthalmologic
      findings suggested bilateral anterior ischemic optic neuropathy (ION) as the
      cause of the visual loss. Although there are numerous reports of ION in the
      setting of hemodynamic compromise, such as systemic hypotension, cases of ION
      associated orthostatic hypotension are very rare. 

PMID- 24082777
TI  - Acute central retinal artery occlusion associated with livedoid vasculopathy: a
      variant of Sneddon's syndrome.
AB  - Livedoid vasculopathy (LV) is characterized by a long history of ulceration of
      the feet and legs and histopathology indicating a thrombotic process. We report a
      case of acute central retinal artery occlusion in a 32-year-old woman who had LV.
      She showed no discernible laboratory abnormalities such as antiphospholipid
      antibodies and no history of cerebrovascular accidents. Attempted intra-arterial
      thrombolysis showed no effect in restoring retinal arterial perfusion or vision.
      The central retinal artery occlusion accompanied by LV in this case could be
      regarded as a variant form of Sneddon's syndrome, which is characterized by
      livedo reticularis and cerebrovascular accidents. 

PMID- 24082778
TI  - A case of Susac syndrome.
AB  - The purpose of this article is to report on the first known Korean case of Susac
      syndrome. An 18-year-old female came to our clinic reporting blurred vision of
      the left eye for 2 days. She also complained of decreased hearing with tinnitus
      of the right ear and mild headache. She was previously healthy and had no
      remarkable medical history. Best-corrected visual acuity was 20 / 50 in the left
      eye and 20 / 20 in the right eye. An axiomatic triad of ocular, cochlear, and
      neurologic involvement was observed in the patient. Fluorescein angiography
      showed branched retinal arterial occlusions in the left eye. A sudden right
      sensorineural hearing loss was observed on audimetry. Magnetic resonance images
      showed a hyperintense lesion in the white matter around the corpus callosum. The
      patient was treated with high doses of systemic corticosteroids, and no
      neuropsychological sequelae were observed. This is the first case report of Susac
      syndrome in Korea. In cases of retinal arterial occlusion with hearing loss or
      neuropsychological symptoms, Susac syndrome should be suspected.

PMID- 24082779
TI  - Choroidal venous pulsations at an arterio-venous crossing in polypoidal choroidal
      vasculopathy.
AB  - It has been reported that pulsations in abnormal vessels are observed on
      indocyanine green (ICG) angiography in half of patients with polypoidal choroidal
      vasculopathy (PCV), although the mechanism of the pulsation is unknown. In this
      study, we report a case of PCV showing venous pulsations at an arterio-venous (A
      V) crossing, and discuss a possible mechanism of polypoidal vessel formation and
      pulsations in PCV. A 66-year-old female presented with a reddish-orange elevated
      lesion and serous retinal detachment in the macula of her left eye, and was
      diagnosed as PCV. She was treated with photodynamic therapy (PDT), and followed
      up through routine examinations, including ICG angiography. ICG angiography at
      presentation showed a branching vascular network and choroidal venules with dye
      leakage (polypoidal vessels) in the left eye. Pulsations, supposedly of venous
      origin, were observed at an A-V crossing in the abnormal vessels. Within 3 months
      after PDT, the polypoidal vessel ceased to leak and the pulsations vanished. The
      reddish-orange lesion gradually decreased in size with complete disappearance of
      retinal detachment. This study suggests that an unusual compression at an A-V
      crossing may make a venule polypoidal, and fluctuations of blood flow and
      pressure in the venule may cause pulsatile movements of the vessel wall. 

PMID- 24082780
TI  - Gyrate atrophy of the choroid and retina diagnosed by ornithine-delta
      aminotransferase gene analysis: a case report.
AB  - A pair of 19-year-old female identical twins was referred to our hospital with
      progressive visual loss. They exhibited bilateral chorioretinal atrophy involving
      the midperiphery on fundoscopy and fluorescein angiography. Bilateral visual
      field constriction was noted on dynamic Goldmann perimetry, and a markedly
      impaired response was observed on both photopic and scotopic electroretinograms.
      Cystoid macular edema was identified in both eyes on optical coherence
      tomography. Plasma levels of ornithine were elevated. Based on these
      observations, the patients were diagnosed with gyrate atrophy of the choroid and
      retina. The clinical diagnosis was confirmed by mutation analysis of the
      ornithine-delta-aminotransferase (OAT) gene. Patients were treated with a
      pyridoxine supplement (300 mg/day) and an arginine-restricted diet to lower
      plasma levels of ornithine, which were successfully reduced without progression
      of chorioretinal atrophy for 15 months. Our report describes the first case of
      gyrate atrophy in the Korean population diagnosed by OAT gene analysis and
      treated with vitamin B6 dietary supplementation.

PMID- 24082781
TI  - Surgical removal of retained subfoveal perfluorocarbon liquid through a
      therapeutic macular hole with intravitreal PFCL injection and gas tamponade.
AB  - We report two cases of surgical removal of a retained subfoveal perfluorocarbon
      liquid (PFCL) bubble through a therapeutic macular hole combined with
      intravitreal PFCL injection and gas tamponade. Two patients underwent pars plana
      vitrectomy with PFCL injection for rhegmatogenous retinal detachment. In both
      cases, a retained subfoveal PFCL bubble was noticed postoperatively by funduscopy
      and optical coherence tomography. Both patients underwent surgical removal of the
      subfoveal PFCL through a therapeutic macular hole and gas tamponade. The
      therapeutic macular holes were completely closed by gas tamponade and the
      procedure yielded a good visual outcome (best-corrected visual acuity of 20 / 40
      in both cases). In one case, additional intravitreal PFCL injection onto the
      macula reduced the size of the therapeutic macular hole and preserved the retinal
      structures in the macula. Surgical removal of a retained subfoveal PFCL bubble
      through a therapeutic macular hole combined with intravitreal PFCL injection and
      gas tamponade provides an effective treatment option.

PMID- 24082783
TI  - Role of indacaterol and the newer very long-acting beta2-agonists in patients
      with stable COPD: a review.
AB  - Bronchodilators are central drugs in the management of patients with chronic
      obstructive pulmonary disease (COPD). Indacaterol was the first agent of the
      novel family of very long-acting beta2-agonists to be used as an inhaled
      bronchodilator for COPD and provides 24-hour therapeutic action, thus allowing
      once-daily administration. Data from clinical trials show that indacaterol has a
      bronchodilator effect similar to that of the anticholinergic tiotropium bromide
      and slightly higher efficacy compared with the long-acting beta2-agonists,
      salmeterol and formoterol. Moreover, the safety profile is excellent and
      comparable with that of placebo. Concerning adherence with drug treatment and
      real-life management in respect to long-acting beta2-agonists, once-daily dosing
      makes indacaterol more convenient for COPD patients and is likely to enhance
      patient adherence. Other very long-acting beta2-agonists currently in development
      include vilanterol, olodaterol, and carmoterol, and these have shown good
      characteristics for clinical use in the studies reported thus far. 

PMID- 24082782
TI  - Vitamin D in asthma and future perspectives.
AB  - Humans have the ability to synthesize vitamin D during the action of ultraviolet
      (UV) radiation upon the skin. Apart from the regulation of calcium and phosphate
      metabolism, another critical role for vitamin D in immunity and respiratory
      health has been revealed, since vitamin D receptors have also been found in other
      body cells. The term "vitamin D insufficiency" has been used to describe low
      levels of serum 25-hydroxyvitamin D that may be associated with a wide range of
      pulmonary diseases, including viral and bacterial respiratory infection, asthma,
      chronic obstructive pulmonary disease, and cancer. This review focuses on the
      controversial relationship between vitamin D and asthma. Also, it has been found
      that different gene polymorphisms of the vitamin D receptor have variable
      associations with asthma. Other studies investigated the vitamin D receptor
      signaling pathway in vitro or in experimental animal models and showed either a
      beneficial or a negative effect of vitamin D in asthma. Furthermore, a range of
      epidemiological studies has also suggested that vitamin D insufficiency is
      associated with low lung function. In the future, clinical trials in different
      asthmatic groups, such as infants, children of school age, and ethnic minorities
      are needed to establish the role of vitamin D supplementation to prevent and/or
      treat asthma. 

PMID- 24082784
TI  - MIOTIC study: a prospective, multicenter, randomized study to evaluate the long
      term efficacy of mobile phone-based Internet of Things in the management of
      patients with stable COPD.
AB  - Chronic obstructive pulmonary disease (COPD) is a common disease that leads to
      huge economic and social burden. Efficient and effective management of stable
      COPD is essential to improve quality of life and reduce medical expenditure. The
      Internet of Things (IoT), a recent breakthrough in communication technology,
      seems promising in improving health care delivery, but its potential strengths in
      COPD management remain poorly understood. We have developed a mobile phone-based
      IoT (mIoT) platform and initiated a randomized, multicenter, controlled trial
      entitled the 'MIOTIC study' to investigate the influence of mIoT among stable
      COPD patients. In the MIOTIC study, at least 600 patients with stable GOLD group
      C or D COPD and with a history of at least two moderate-to-severe exacerbations
      within the previous year will be randomly allocated to the control group, which
      receives routine follow-up, or the intervention group, which receives mIoT
      management. Endpoints of the study include (1) frequency and severity of acute
      exacerbation; (2) symptomatic evaluation; (3) pre- and post-bronchodilator forced
      expiratory volume in 1 second (FEV1) and FEV1/forced vital capacity (FVC)
      measurement; (4) exercise capacity; and (5) direct medical cost per year. Results
      from this study should provide direct evidence for the suitability of mIoT in
      stable COPD patient management. 

PMID- 24082786
TI  - Counseling, quality of life, and acute postoperative pain in elderly patients
      with hip fracture.
AB  - INTRODUCTION: Hip fractures represent one of the most important causes of
      morbidity and mortality in elderly people. Anxiety and depression affect their
      quality of life and increase pain severity, and have adverse effects on
      functional recovery. Recent World Health Organization guidelines emphasize that
      therapeutic regimes need to be individualized and combined with psychological
      support. This study was launched with the primary endpoint of assessing if and to
      what extent client-centered therapy affects the perception of pain, reduces
      anxiety and depression, and increases the quality of life of elderly patients
      with hip fracture. MATERIALS AND METHODS: Forty patients were admitted to the
      Orthopedic and Trauma Surgery ward for hip fracture. Patients were randomly
      divided into two subgroups: (1) case (group C), had to receive patient-centered
      counseling throughout the hospitalization; and (2) control (group NC), receiving
      the analgesic treatment without receiving counseling. Short Form-36-item Health
      Survey Questionnaire, State-Trait Anxiety Inventory, and Hamilton Rating Scale
      for Depression scores were recorded before any treatment, at discharge, and after
      30 days. Pain levels were evaluated by means of Visual Analog Scale every 12
      hours during the hospitalization from the day of surgery until day 5. RESULTS:
      The hierarchical clustering analysis identified before any treatment were two
      clusters based on different physical functioning perceptions and role
      limitations, which were due to physical and emotional problems. Counseling did
      have a positive impact on quality of life on all patients, but in a more relevant
      way if patients were low functioning upon admittance to the ward. Anxiety and
      depression decreased in patients undergoing counseling, and their pain levels
      were lower than among patients not receiving it. CONCLUSION: This study reveals
      that hip fracture patients can be clustered on the basis of Short Form-36
      baseline scores. Counseling affects the evolution of mental and physical status
      in these patients, and the major benefit is reported in patients whose quality of
      life perception is worse after the trauma. Decreasing anxiety and depression
      levels, as well as more satisfying pain management, assessed by means of specific
      tests, confirm the effectiveness of counseling in elderly patients with hip
      fracture.

PMID- 24082787
TI  - Multidisciplinary management of patent foramen ovale (PFO) and cryptogenic
      stroke/TIA.
AB  - PURPOSE: Patent foramen ovale (PFO) has been implicated as a risk factor for
      cryptogenic ischemic stroke (CS). However, there is still a lack of widely
      accepted, undisputed indications for PFO closure. The present study describes the
      concept of the multidisciplinary PFO conference and a decision making process for
      closure versus no closure that was developed into a formalized clinical
      algorithm, and presents the results of implementing these, in terms of number and
      proportion of PFO closures as well as repeat referrals. DESIGN: Five specialists
      in neurology, cardiology, internal medicine, thromboembolism, and
      echocardiography evaluated the clinical data of 311 patients at PFO conferences
      during 2006 to 2009. The main criteria for closure were patients with first-ever
      CS with PFO and atrial septal aneurysm, or patients with recurrent CS and PFO
      without atrial septal aneurysm. RESULTS: A total of 143 patients (46%) were
      accepted for closure and 167 patients were rejected. Patients accepted for
      closure were younger (mean 50 years versus 58 years) (P < 0.001). The acceptance
      rate for PFO closure was similar throughout these years, with an average of 45%.
      Three of 167 patients (1.8%) initially rejected for PFO closure were re-referred
      due to recurrent stroke, and the PFO closure was subsequently performed.
      CONCLUSION: The acceptance rate of less than 50% in the present study underscores
      the complex relationship between CS and PFO. Whatever the criteria used for PFO
      closure, any unit caring for these patients needs to have a rigorous process to
      avoid overtreatment as well as undertreatment and to ensure that personal
      preferences and economic incentives do not steer the selection process. Our
      algorithm provides a stable acceptance rate and a low rate of repeat referrals.

PMID- 24082785
TI  - A review of the benefits of early treatment initiation with single-pill
      combinations of telmisartan with amlodipine or hydrochlorothiazide.
AB  - This review discusses the rationale for earlier use of single-pill combinations
      (SPCs) of antihypertensive drugs, with a focus on telmisartan/amlodipine (T/A)
      and telmisartan/hydrochlorothiazide (T/H) SPCs. Compared with the respective
      monotherapies, the once-daily T/A and T/H SPCs have been shown to result in
      significantly higher blood pressure (BP) reductions, BP goal rates, and response
      rates in patients at all stages of hypertension. As expected, BP reductions are
      highest with the highest dose (T80/A10 and T80/H25) SPCs. Subgroup analyses of
      the telmisartan trials have reported the efficacy of both SPCs to be consistent,
      regardless of the patients' age, race, and coexisting diabetes, obesity, or renal
      impairment. In patients with mild-to-moderate hypertension, the T/A combination
      provides superior 24-hour BP-lowering efficacy compared with either treatment
      administered as monotherapy. Similarly, the T/H SPC treatment provides superior
      24-hour BP-lowering efficacy, especially in the last 6 hours relative to other
      renin-angiotensin system inhibitor-based SPCs. The T/A SPC is associated with a
      lower incidence of edema than amlodipine monotherapy, and the T/H SPC with a
      lower incidence of hypokalemia than hydrochlorothiazide monotherapy. Existing
      evidence supports the use of the T/A SPC for the treatment of hypertensive
      patients with prediabetes, diabetes, or metabolic syndrome, due to the metabolic
      neutrality of both component drugs, and the use of the T/H SPC for those patients
      with edema or in need of volume reduction. 

PMID- 24082788
TI  - Experiences by patients and health professionals of a multidisciplinary
      intervention for long-term orofacial pain.
AB  - The aim of the present study was to describe patients' and health professionals'
      experiences of a multidisciplinary stress-focused clinical evaluation with
      prolonged engagement as an intervention for patients with long-term orofacial
      pain. Data in the patient part of this study were collected by free-text
      questionnaires using open-ended questions. Data were collected by group interview
      in the part of the study concerning health professionals. All data were analyzed
      according to qualitative content analysis. Data from patients revealed three
      categories for the intervention, ie, "helpful for most and crucial for some",
      "being listened to, respected and validated", and "gives important coping
      strategies". The results showed that a vast majority of patients described
      themselves as having been helped by the intervention. Some patients reported that
      meeting with the orofacial pain consultant team was crucial to the future course
      of their lives. Most patients described still having residual pain and symptoms,
      and only a few described their pain as being fully remitted. However, because of
      the intervention, the patients reported being able to adopt more constructive
      coping strategies. They also described their perception of the pain as being
      different, in that it was not so frightening once they had been given a model
      with which to understand it. Data from the health professionals revealed similar
      categories. Concordance between the patients' and health professionals'
      experiences was striking. In their descriptions, the health professionals and
      patients underscored the same components as being effective, with understanding,
      respect, and validation being the most important. The multidisciplinary approach
      was highlighted as being key to success by both the patients and health
      professionals. 

PMID- 24082789
TI  - Risk factors for infections with extended-spectrum beta-lactamase-producing
      Escherichia coli in a county of Southern Sweden.
AB  - BACKGROUND: It is important to identify patients who are at risk for infections
      with extended-spectrum beta-lactamase (ESBL)-producing bacteria in order to
      reduce mortality, to avoid spread of resistant bacteria in hospitals, and to
      minimize the number of patients receiving unnecessary treatment with broad
      spectrum antibiotics. A case-control survey among Swedish patients was performed
      at Skane University Hospital to identify risk factors for developing an infection
      with ESBL-producing Escherichia coli in a low endemic country. METHODS: We used a
      computerized database to identify patients with growth of ESBL-producing E. coli
      (n = 109) in urine or blood cultures and an equal number of controls matched for
      age and gender with non ESBL-producing E. coli in urine and blood diagnosed
      between January and October 2008. We used unadjusted P-values. RESULTS: Patients
      with ESBL-producing E. coli had a significantly (P < 0.05) higher likelihood of
      having traveled to Asia including Turkey and the Middle East including Egypt
      (14/58) than the non-ESBL-positive group (4/53). Hospital stay during the
      previous year (P < 0.04), especially for more than one month, was another
      significant (P = 0.01) risk factor for infection with ESBL-producing E. coli
      (8/58). A stay in the surgical department was a further risk factor (P < 0.01).
      CONCLUSION: In this study, we identified 22 of 58 (38%) patients with ESBL
      producing E. coli by considered significant risk factors before starting
      antibiotics.

PMID- 24082792
TI  - Metabolic syndrome in hemodialysis patients as a risk factor for new-onset
      diabetes mellitus after renal transplant: a prospective observational study.
AB  - PURPOSE: Metabolic syndrome is a cluster of biochemical abnormalities including
      cardiovascular and diabetes risk factors. The development of diabetes mellitus
      after renal transplant represents a major posttransplant complication that may
      adversely affect graft/patient survival. The aim of this study was to assess the
      role of metabolic syndrome in patients on hemodialysis as a risk factor for the
      incidence of new-onset diabetes mellitus after renal transplant. PATIENTS AND
      METHODS: This was a prospective observational epidemiologic study carried out in
      adult nondiabetic patients undergoing chronic hemodialysis and on the renal
      transplant waiting list between November 2008 and April 2009. Patients were
      followed up from Visit 1 (baseline) to 6 months after the renal transplant. The
      analysis of the role of metabolic syndrome in hemodialysis patients as a risk
      factor for the incidence of new-onset diabetes mellitus after renal transplant
      included the estimation of relative risk and its 95% confidence interval (CI).
      RESULTS: A total of 383 evaluable patients were entered into the study (mean age,
      52.7 years; male, 57.7%; Caucasian, 90.1%). The prevalence of metabolic syndrome
      on hemodialysis was 30.4% (95% CI, 25.8%-35.4%). Hypertension was the most
      prevalent criterion for metabolic syndrome (65.0%), followed by low levels of
      high-density lipoprotein cholesterol (52.7%), abdominal obesity (36.2%),
      hypertriglyceridemia (32.4%), and impaired glucose (8.9%). After the renal
      transplant, the prevalence of metabolic syndrome was still 25.8%. During the
      posttransplant period, the incidence of new-onset diabetes mellitus reached 13.0%
      (95% CI, 7.8%-20.6%) and patients with pretransplant metabolic syndrome were 2.6
      times (95% CI, 1.043-6.608) more likely to develop new-onset diabetes mellitus
      after the renal transplant than those without metabolic syndrome. CONCLUSION: The
      presence of metabolic syndrome in patients undergoing hemodialysis represents an
      independent risk factor for the incidence of new-onset diabetes mellitus after
      renal transplant.

PMID- 24082793
TI  - Use of recombinant human antithrombin concentrate in pregnancy.

PMID- 24082791
TI  - Prevalence of hypertension and obesity in patients with type 2 diabetes mellitus
      in observational studies: a systematic literature review.
AB  - BACKGROUND: Hypertension and obesity are known to contribute, directly or
      indirectly, to the development of long-term complications of type 2 diabetes
      mellitus (T2DM). Knowing the prevalence of these comorbidities is important for
      determining the size of the population that may benefit from strategies that
      reduce blood pressure and weight while controlling blood glucose. METHODS: In
      this systematic literature review, electronic searches of PubMed, Embase, and the
      Cochrane Library were conducted to identify observational studies of hypertension
      and/or obesity prevalence in patients with T2DM throughout the world. The
      searches were limited to studies reported in English from January 1, 2001 to
      February 16, 2012. RESULTS: From a total of 2,688 studies, 92 observational
      studies provided prevalence rates for hypertension and/or obesity specifically in
      adults with T2DM. Fifteen studies of specific subtypes of hypertension or
      subpopulations with T2DM were subsequently excluded, leaving 78 studies (in 77
      articles) for inclusion in this article. Of these, 61studies reported
      hypertension prevalence, 44 reported obesity prevalence, and 12 reported the
      prevalence of hypertension with obesity. Most studies had a low risk of bias
      regarding diagnosis of T2DM (70/78), hypertension (59/69), or obesity (45/47).
      The continental regions with the most observational studies of hypertension or
      obesity prevalence were Europe (n = 30) and Asia (n = 26). Hypertension rates
      typically were high in all regions; most studies presented rates above 50%, and
      many presented rates above 75%. Obesity rates exceeded 30% in 38 of 44 studies
      and 50% in 14 of 44 studies, especially those assessing central obesity (based on
      waist circumference). Among obese adults, hypertension rates were at or above 70%
      in Asia and above 80% in Europe; rates were lower in North and South America but
      still above 30%. CONCLUSION: Around the world, hypertension and obesity,
      separately or together, are common comorbidities in adults with T2DM.

PMID- 24082790
TI  - The use of platensimycin and platencin to fight antibiotic resistance.
AB  - Infectious diseases are known as one of the most life-threatening disabilities
      worldwide. Approximately 13 million deaths related to infectious diseases are
      reported each year. The only way to combat infectious diseases is by chemotherapy
      using antimicrobial agents and antibiotics. However, due to uncontrolled and
      unnecessary use of antibiotics in particular, surviving bacteria have evolved
      resistance against several antibiotics. Emergence of multidrug resistance in
      bacteria over the past several decades has resulted in one of the most important
      clinical health problems in modern medicine. For instance, approximately 440,000
      new cases of multidrug-resistant tuberculosis are reported every year leading to
      the deaths of 150,000 people worldwide. Management of multidrug resistance
      requires understanding its molecular basis and the evolution and dissemination of
      resistance; development of new antibiotic compounds in place of traditional
      antibiotics; and innovative strategies for extending the life of antibiotic
      molecules. Researchers have begun to develop new antimicrobials for overcoming
      this important problem. Recently, platensimycin - isolated from extracts of
      Streptomyces platensis - and its analog platencin have been defined as promising
      agents for fighting multidrug resistance. In vitro and in vivo studies have shown
      that these new antimicrobials have great potential to inhibit methicillin
      resistant Staphylococcus aureus, vancomycin-resistant enterococci, and penicillin
      resistant Streptococcus pneumoniae by targeting type II fatty acid synthesis in
      bacteria. Showing strong efficacy without any observed in vivo toxicity increases
      the significance of these antimicrobial agents for their use in humans. However,
      at the present time, clinical trials are insufficient and require more research.
      The strong antibacterial efficacies of platensimycin and platencin may be
      established in clinical trials and their use in humans for coping with multidrug
      resistance may be allowed in the foreseeable future. 

PMID- 24082794
TI  - Brief research report: sociodemographic factors associated with HIV status among
      African American women in Washington, DC.
AB  - INTRODUCTION: African American women living in Washington, DC have one of the
      highest Human immunodeficiency virus (HIV) incidence rates in the US. However,
      this population has been understudied, especially as it relates to factors
      associated with HIV status. METHODS: This cross-sectional study examined
      sociodemographic factors that were associated with having a negative or positive
      HIV status among a sample of 115 African American women between the ages of 24
      and 44 years. We assessed such factors as age, education, sexual orientation,
      household income, sources of income, number of children, length of residency
      tenure in Washington, DC, and level of HIV-prevention knowledge. RESULTS: Among
      the overall sample, 53 women self-identified as HIV-positive and 62 as HIV
      negative. Compared to their HIV-negative counterparts, women who reported being
      HIV-positive were less educated, had lower household income, and had longer
      residency tenure in Washington, DC. There were no differences in HIV knowledge
      between HIV-positive and -negative study participants. CONCLUSION: These findings
      may provide important directions for targeting specific subpopulations of African
      Americans for HIV-prevention/intervention programs.

PMID- 24082795
TI  - Medical abortion practices among private providers in Vietnam.
AB  - OBJECTIVE: To describe medical abortion (MA) practices among private providers in
      Vietnam. METHODS: The study subjects were women (n = 258) undergoing early MA
      through 12 private providers in Hanoi during February-June 2012. The women were
      interviewed on the day of their procedure and were followed up by telephone 14
      days after mifepristone administration. RESULTS: Of the 258 women in the study,
      97% used a regimen of mifepristone plus misoprostol; 80% were instructed to
      administer misoprostol at home. MA resulted in a complete termination in 90.8% of
      cases. All women were provided with information on potential complications and
      were instructed to return for a follow-up visit. We successfully followed up
      77.5% (n = 200) of participants by telephone, while nearly two-thirds of women
      returned to the clinic for a follow-up visit. At follow-up, 39.5% of women
      reported having used a Help line service, while 7% had sought help from a health
      provider. A high unmet need for postabortion family planning was identified.
      CONCLUSION: Follow-up of women, postabortion care, and the provision of family
      planning have been identified as important areas to address for strengthening MA
      services in the private sector in Vietnam.

PMID- 24082797
TI  - Effects of an intervention to reduce insecticide exposure on insecticide-related
      knowledge and attitude: a quasi-experimental study in Shogun orange farmers in
      Krabi Province, Thailand.
AB  - An intervention to reduce insecticide exposure in Shogun orange farmers was
      implemented in Krabi Province, Thailand. Intervention effects on insecticide
      related knowledge and attitude were evaluated in a quasi-experimental study in
      two farms about 20 kilometers (km) apart. The intervention was conducted at one
      farm; the other served as control. The study included 42 and 50 farmers at the
      intervention and control farms, respectively. The intervention included several
      components, including didactic instruction, practical demonstrations, use of a
      fluorescent tracer, and continuing guidance on insecticide use via a small,
      specially trained group within the overall intervention group. To the best of our
      knowledge, this was the first such intervention in Thailand. Knowledge and
      attitude were measured at baseline (pre-intervention), and at 2 and 5 months
      after the intervention (follow-up 1 and follow-up 2, respectively). Intervention
      effects were assessed with linear mixed models, specified to enable testing of
      effects at each follow-up time. The intervention was associated with substantial
      and statistically significant improvements in both knowledge score and attitude
      score (P < 0.001 for each score at each follow-up time). Intervention-related
      improvements in knowledge score and attitude score were equivalent to about 27%
      and 14% of baseline mean knowledge and attitude scores, respectively.
      Intervention-related benefits were similar at both follow-up times. Findings were
      similar before and after adjustment for covariates. These findings increase
      confidence that well-designed interventions can reduce farmers' insecticide
      exposure in Thailand and elsewhere. In future research, it would be desirable to
      address long-term intervention effects on farmers' health and quality of life. 

PMID- 24082796
TI  - The long-term outcomes of interventions for the management of attention-deficit
      hyperactivity disorder in children and adolescents: a systematic review of
      randomized controlled trials.
AB  - PURPOSE: To systematically identify and review the currently available evidence
      on the long-term outcomes of recommended attention-deficit hyperactivity disorder
      (ADHD) interventions following randomized controlled trials with children and
      young people. METHOD: A systematic search was conducted to identify trials >1
      year in length using the following databases: CINAHL (January 1982- July 2012),
      MEDLINE (Ovid and Cambridge Scientific Abstracts [CSA]), Psych info, Science
      Direct (Elsevier), and Cochrane Library. Hand searches of key journals in the
      subject, book chapters, and conference proceedings were also carried out.
      Relevant papers were critically appraised using the Cochrane risk of bias tool.
      RESULTS: Eight controlled trials were identified as being relevant, of duration
      ranging from 1 year to 8 years (at follow up). The total number of participants
      in the studies was 1,057, of whom 579 (54.7%) were from one cohort and included
      26 different outcome measures. Results suggest there is moderate-to-high-level
      evidence that combined pharmacological and behavioral interventions, and
      pharmacological interventions alone can be effective in managing the core ADHD
      symptoms and academic performance at 14 months. However, the effect size may
      decrease beyond this period. CONCLUSION: This review has highlighted the paucity
      and limitations of the evidence investigating the long-term outcomes of
      recommended interventions for managing ADHD symptoms. There is little evidence to
      suggest that the effects observed over the relatively short term are maintained
      throughout longer periods of impairment. Furthermore, much of the existing
      evidence examining effectiveness beyond 12 months does not include newer
      medications currently available or consider significant contextual and cultural
      differences, such as UK/European and Asian populations. Longitudinal studies are
      required to examine the long-term outcomes for children and young people with
      ADHD managed with currently recommended service interventions. They should also
      include the whole spectrum of ADHD, with its full range of coexisting conditions,
      and cultural and contextual diversity.

PMID- 24082798
TI  - Symptom burden and job absenteeism after treatment with additional catheter
      directed thrombolysis for deep vein thrombosis.
AB  - INTRODUCTION: Additional catheter-directed thrombolysis (CDT) for acute deep vein
      thrombosis (DVT) reduces long-term postthrombotic syndrome and is likely to
      represent a cost-effective alternative treatment compared to the standard
      treatment of anticoagulation and elastic compression stockings. Accelerated
      thrombus resolution has also been suggested to improve symptoms and patient
      function in the acute phase. We aimed to investigate whether additional CDT led
      to fewer symptoms and job absenteeism during the first 6 months after initiation
      of DVT treatment compared to standard treatment alone. METHODS: The Catheter
      directed Venous Thrombolysis (CaVenT) study was a multicenter open label,
      randomized controlled trial of patients ages 18 years to 75 years with a verified
      high proximal DVT, <21 days of symptoms, and no apparent bleeding risk. Patients
      were allocated to additional CDT or to standard treatment only. Symptoms were
      assessed at baseline and at 6 months using items from the generic and disease
      specific quality of life questionnaires EQ-5D and VEINES-QOL/Sym, respectively.
      Individual data on sickness benefits related to venous thromboembolic disease
      were obtained from the national welfare service. RESULTS: A total of 90 patients
      allocated additional CDT and 99 control patients completed long-term follow-up
      and were included in the analyses. Twenty-four in the CDT arm and 40 controls
      received sick leave (P = 0.046). When considering working patients only (54 in
      the CDT arm and 72 controls) this difference was no longer statistically
      significant. Mean duration of job absenteeism was 86.4 days (95% confidence
      interval 59.4-113.5) in the CDT arm and 60.1 days (95% confidence interval 42.3
      77.8) in controls (P = 0.072). After 6 months, more controls experienced frequent
      swelling of the leg compared with those allocated to CDT (47 [49.0%] patients
      versus 25 [29.4%] patients, respectively, [P = 0.007]). CONCLUSION: There are
      limitations to our data, but the findings indicate improved symptom relief and
      less frequent job absenteeism in patients treated with additional CDT; this
      expands upon previously established benefits from this treatment.

PMID- 24082799
TI  - Influenza vaccine recommendations for children and youth for the 2012/2013
      season.

PMID- 24082800
TI  - Reflections on a career as a paediatrician.

PMID- 24082801
TI  - Dr noni macdonald award.

PMID- 24082802
TI  - Computer/gaming station use in youth: Correlations among use, addiction and
      functional impairment.
AB  - OBJECTIVE: Computer/gaming station use is ubiquitous in the lives of youth today.
      Overuse is a concern, but it remains unclear whether problems arise from
      addictive patterns of use or simply excessive time spent on use. The goal of the
      present study was to evaluate computer/gaming station use in youth and to examine
      the relationship between amounts of use, addictive features of use and functional
      impairment. METHOD: A total of 110 subjects (11 to 17 years of age) from local
      schools participated. Time spent on television, video gaming and non-gaming
      recreational computer activities was measured. Addictive features of
      computer/gaming station use were ascertained, along with emotional/behavioural
      functioning. Multiple linear regressions were used to understand how youth
      functioning varied with time of use and addictive features of use. RESULTS: Mean
      (+/- SD) total screen time was 4.5+/-2.4 h/day. Addictive features of use were
      consistently correlated with functional impairment across multiple measures and
      informants, whereas time of use, after controlling for addiction, was not.
      CONCLUSIONS: Youth are spending many hours each day in front of screens. In the
      absence of addictive features of computer/gaming station use, time spent is not
      correlated with problems; however, youth with addictive features of use show
      evidence of poor emotional/ behavioural functioning.

PMID- 24082803
TI  - A qualitative study of predelivery counselling for extreme prematurity.
AB  - OBJECTIVE: To ascertain from parents of neonates born before 27 weeks'
      gestational age how to improve predelivery counselling for delivery room
      resuscitation. METHODS: Qualitative ethnographic study using semistructured, face
      to-face interviews of 10 families. Data were analyzed using a constant
      comparative method. RESULTS: Parents had no previous knowledge about prematurity.
      They would have preferred prioritized information during predelivery counselling
      focused on the immediate risks to their child. Resuscitation wishes were
      inconsistently sought. Opportunities for repeat discussions involving both
      parents were often missed. Parents agreed that the opportunity to explicitly
      state resuscitation wishes should be offered. Additional materials, such as
      pamphlets or videos, would improve counselling. CONCLUSIONS: Information about
      prematurity should be offered when the pregnancy is deemed high risk, with repeat
      counselling opportunities for both parents to discuss options. Once the decision
      is made to resuscitate, parents want the neonatal team to convey a message of
      hope and compassion.

PMID- 24082805
TI  - Personal reflections on end-of-life care in a newborn infant.

PMID- 24082804
TI  - Celiac disease and cardiomyopathy in an adolescent with occult cirrhosis.
AB  - Patients with celiac disease commonly present with gastrointestinal symptoms
      including abdominal pain, bloating, constipation or diarrhea. Extraintestinal
      manifestations of this small bowel disease are increasingly recognized, and
      greater numbers of patients are being diagnosed after presenting solely with
      nongastrointestinal symptoms. The present report describes a case involving a 16
      year-old girl with oligomenorrhea who was found to have celiac disease and liver
      cirrhosis of unknown etiology. Subsequent evaluation revealed cardiac dysfunction
      consistent with cirrhotic cardiomyopathy, a rare finding in the paediatric
      population. This patient's unusual presentation permits an exploration of several
      conditions uncommonly reported in conjunction with celiac disease. 

PMID- 24082807
TI  - Counselling and management for anticipated extremely preterm birth.
AB  - Extremely preterm birth (birth between 22(0/7) and 25(6/7) weeks' gestational age
      [GA]) often requires parents to make complex choices about the care of their
      infant. Health professionals have a significant role in providing information,
      guidance and support. Parents facing the birth of an extremely preterm infant
      should have the chance to meet with both obstetrical and paediatric/neonatal care
      providers to receive accurate information about their infant's prognosis,
      provided with clarity and compassion. Decision making between parents and health
      professionals should be an informed and shared process, with documentation of all
      management decisions. Consultation with and transfer to tertiary perinatal
      centres are important for the care of both mother and fetus. As the survival of
      infants born before or at 22 completed weeks' GA remains uncommon, a
      noninterventional approach is recommended, whereas at 23, 24 and 25 weeks' GA,
      counselling about outcomes and decision making should be individualized for each
      infant and family, using factors which influence prognosis. All extremely preterm
      infants who are not resuscitated, or for whom resuscitation is not successful,
      must receive compassionate palliative care. 

PMID- 24082806
TI  - Can surveillance provide epidemiological data on Aboriginal health?

PMID- 24082808
TI  - The toddler who is falling off the growth chart.
AB  - Growth monitoring is an essential part of paediatric health care, from birth
      through adolescence. Growth and nutritional problems often occur between 18
      months and three years of age. Health care professionals involved in the care of
      children need to follow growth closely in this period, be able to evaluate a
      toddler whose growth seems to be faltering, and know when and how to intervene. 

PMID- 24082809
TI  - The 'picky eater': The toddler or preschooler who does not eat.
AB  - The majority of children between one and five years of age who are brought in by
      their parents for refusing to eat are healthy and have an appetite that is
      appropriate for their age and growth rate. Unrealistic parental expectations may
      result in unnecessary concern, and inappropriate threats or punishments may
      aggravate a child's refusal to eat. A detailed history and general physical
      examination are necessary to rule out acute and chronic illnesses. A food diary
      and assessment of parental expectations about eating behaviour should be
      completed. Where the child's 'refusal' to eat is found to be related to
      unrealistic expectations, parents should be reassured and counselled about the
      normal growth and development of children at this age. 

PMID- 24082810
TI  - Health care professionals' attitudes about pregnancy termination for different
      fetal anomalies.
AB  - BACKGROUND: Health care professionals (HCPs) may be involved in counselling women
      after an antenatal diagnosis of various fetal anomalies. Many pregnant women
      consider termination of pregnancy (TOP) after antenatal diagnosis of various
      fetal anomalies. Little is known, however, about the attitudes of HCPs regarding
      TOP for specific antenatal diagnoses. OBJECTIVE: To determine the attitudes and
      opinions of HCPs in maternal and child health regarding TOP for fetal anomalies
      of varying severity. METHODS: AN ANONYMOUS QUESTIONNAIRE WAS DISTRIBUTED TO FOUR
      GROUPS OF HCPS: obstetric residents; paediatric residents; delivery room nurses;
      and neonatal intensive care nurses. Respondents were asked about TOP if they or
      their spouse were to receive an antenatal diagnosis for five prenatally diagnosed
      conditions: trisomy 21; trisomy 18; cleft lip and palate; Turner syndrome; and
      hypoplastic left heart syndrome. RESULTS: Two hundred eighty HCPs answered the
      questionnaire (90% response rate). Ten per cent of respondents would not consider
      TOP under any of the circumstances described. Among those who would consider TOP,
      they were most likely to do so for trisomy 18 and least likely for cleft lip and
      palate, and fairly evenly divided among the remaining three conditions
      (hypoplastic left heart syndrome [65%], trisomy 21 [56%] and Turner syndrome
      [37%]). Paediatric residents were less likely to choose TOP than other groups and
      obstetrics residents were most likely. CONCLUSIONS: Attitudes of HCPs toward TOP
      vary according to prenatally identified condition and professional group. More
      rigorous analysis should be performed regarding the process of counselling and
      the impact of HCPs beliefs on parental decisions.

PMID- 24082811
TI  - Healthy Child Uganda survey of knowledge, attitude and behaviour of village
      health team members toward their health care responsibilities in southwest
      Uganda.

PMID- 24082812
TI  - [Not Available].

PMID- 24082813
TI  - [Not Available].
AB  - BACKGROUND: The use of antipsychotics, especially second-generation
      antipsychotics (SGAs), for children with mental health disorders in Canada has
      increased dramatically over the past five years. These medications have the
      potential to cause major metabolic and neurological complications with chronic
      use. OBJECTIVE: To synthesize the evidence for specific metabolic and
      neurological side effects associated with the use of SGAs in children, and
      provide evidence-based recommendations for the monitoring of these side effects.
      METHODS: A systematic review of controlled clinical trials of SGAs involving
      children was performed. Recommendations for monitoring SGA safety were made
      according to a classification scheme based on the GRADE (Grading of
      Recommendations Assessment, Development and Evaluation) system. When there was
      inadequate evidence, recommendations were based on consensus and expert opinion.
      A multidisciplinary consensus group reviewed all relevant evidence and reached
      consensus on the recommendations. RESULTS: The present guidelines provide
      evidence-based recommendations for monitoring SGA safety. The strength of
      recommendations for specific physical examination manoeuvres and laboratory tests
      are provided for each SGA medication at specific time points. CONCLUSION:
      Multiple randomized controlled trials evaluated the efficacy of many of the SGAs
      in paediatric mental health disorders. These benefits, however, are not without
      risks - both metabolic and neurological side effects occur in children treated
      with SGAs. The risk of weight gain, increased body mass index and abnormal lipid
      levels is greatest with olanzapine, followed by clozapine and quetiapine. The
      risk of neurological side effects of the treatment is greatest with risperidone,
      olanzapine and aripiprazole. Appropriate monitoring procedures for adverse
      effects will improve the quality of care of children treated with these
      medications.

PMID- 24082815
TI  - [Not Available].
AB  - BACKGROUND: Second-generation antipsychotics are commonly associated with
      metabolic complications. These medications are being used more frequently for the
      treatment of mental health disorders in children, which has stimulated the need
      for creating formal guidelines on monitoring their safety and effectiveness.
      Previous guidelines have been developed for monitoring metabolic and neurological
      complications. To assist practitioners who perform these monitoring procedures, a
      complementary set of treatment recommendations have been created for situations
      in which abnormal measurements or results are encountered. OBJECTIVE: To create
      evidence-based recommendations to assist in managing metabolic complications in
      children being treated with second-generation antipsychotics. METHODS: A
      systematic review of the literature on metabolic complications of second
      generation antipsychotic medications in children was conducted. Members of the
      consensus group evaluated the information gathered from the systematic review of
      the literature and used a nominal group process to reach a consensus on treatment
      recommendations. Wherever possible, references were made to existing guidelines
      on the evaluation and treatment of metabolic abnormalities in children. RESULTS:
      Evidence-based recommendations are presented to assist in managing metabolic
      complications including weight gain; increased waist circumference; elevation in
      prolactin, cholesterol, triglyceride and glucose levels; abnormal liver function
      tests; and abnormal thyroid studies. CONCLUSION: The use of second-generation
      antipsychotics requires proper monitoring procedures. The present treatment
      guideline provides guidance to clinicians on the clinical management of metabolic
      complications if they occur.

PMID- 24082814
TI  - [Not Available].
AB  - BACKGROUND/OBJECTIVE: Antipsychotic use in children is increasing. The purpose of
      the present article is to provide guidance to clinicians on the clinical
      management of extrapyramidal side effects of second-generation antipsychotics.
      METHODS: Published literature, key informant interviews, and discussions with
      panel members and stakeholder partners were used to identify key clinical areas
      of guidance and preferences on format for the present recommendations. Draft
      recommendations were presented to a guideline panel. Members of the guideline
      panel evaluated the information gathered from the systematic review of the
      literature and used a nominal group process to reach a consensus on treatment
      recommendations. A description of the neurological abnormalities commonly seen
      with antipsychotic medications is provided, as well as recommendations on how to
      examine and quantify these abnormalities. A stepwise approach to the management
      of neurological abnormalities is provided. RESULTS: Several different types of
      extrapyramidal symptoms can be seen secondary to antipsychotic use in children
      including neuroleptic-induced acute dystonia, neuroleptic-induced akathisia,
      neuroleptic-induced parkinsonism, neuroleptic-induced tardive dyskinesia, tardive
      dystonia and tardive akathisia, and withdrawal dyskinesias. The overwhelming
      majority of evidence on the treatment of antipsychotic-induced movement disorders
      is derived from adult patients with schizophrenia. Given the scarcity of
      paediatric data, recommendations were made with reference to both the adult and
      paediatric literature. Given the limitations in the generalizability of data from
      adult subjects to children, these recommendations should be considered on the
      basis of expert opinion, rather than evidence based. CONCLUSION: Clinicians must
      be aware of the potential of second-generation antipsychotics to induce
      neurological side effects, and should exercise a high degree of vigilance when
      prescribing these medications.

PMID- 24082816
TI  - Osteosarcoma: lessons learned and future avenues.

PMID- 24082817
TI  - Sporadic versus Radiation-Associated Angiosarcoma: A Comparative
      Clinicopathologic and Molecular Analysis of 48 Cases.
AB  - Angiosarcomas are aggressive tumors of vascular endothelial origin, occurring
      sporadically or in association with prior radiotherapy. We compared
      clinicopathologic and biologic features of sporadic angiosarcomas (SA) and
      radiation-associated angiosarcomas (RAA). Methods. From a University of Michigan
      institutional database, 37 SA and 11 RAA were identified. Tissue microarrays were
      stained for p53, Ki-67, and hTERT. DNA was evaluated for TP53 and ATM mutations.
      Results. Mean latency between radiotherapy and diagnosis of RAA was 11.9 years:
      6.7 years for breast RAA versus 20.9 years for nonbreast RAA (P = 0.148).
      Survival after diagnosis did not significantly differ between SA and RAA (P =
      0.590). Patients with nonbreast RAA had shorter overall survival than patients
      with breast RAA (P = 0.03). The majority of SA (86.5%) and RAA (77.8%) were
      classified as high-grade sarcomas (P = 0.609). RAA were more likely to have well
      defined vasoformative areas (55.6% versus 27%, P = 0.127). Most breast SA were
      parenchymal in origin (80%), while most breast RAA were cutaneous in origin
      (80%). TMA analysis showed p53 overexpression in 25.7% of SA and 0% RAA, high Ki
      67 in 35.3% of SA and 44.4% RAA, and hTERT expression in 100% of SA and RAA. TP53
      mutations were detected in 13.5% of SA and 11.1% RAA. ATM mutations were not
      detected in either SA or RAA. Conclusions. SA and RAA are similar in histology,
      immunohistochemical markers, and DNA mutation profiles and share similar
      prognosis. Breast RAA have a shorter latency period compared to nonbreast RAA and
      a significantly longer survival. 

PMID- 24082818
TI  - Letter to the editor by megan Hall.

PMID- 24082819
TI  - MutS Homologues hMSH4 and hMSH5: Genetic Variations, Functions, and Implications
      in Human Diseases.
AB  - The prominence of the human mismatch repair (MMR) pathway is clearly reflected by
      the causal link between MMR gene mutations and the occurrence of Lynch syndrome
      (or HNPCC). The MMR family of proteins also carries out a plethora of diverse
      cellular functions beyond its primary role in MMR and homologous recombination.
      In fact, members of the MMR family of proteins are being increasingly recognized
      as critical mediators between DNA damage repair and cell survival. Thus, a better
      functional understanding of MMR proteins will undoubtedly aid the development of
      strategies to effectively enhance apoptotic signaling in response to DNA damage
      induced by anti-cancer therapeutics. Among the five known human MutS homologs,
      hMSH4 and hMSH5 form a unique heterocomplex. However, the expression profiles of
      the two genes are not correlated in a number of cell types, suggesting that they
      may function independently as well. Consistent with this, these two proteins are
      promiscuous and thought to play distinct roles through interacting with different
      binding partners. Here, we describe the gene and protein structures of eukaryotic
      MSH4 and MSH5 with a particular emphasis on their human homologues, and we
      discuss recent findings of the roles of these two genes in DNA damage response
      and repair. Finally, we delineate the potential links of single nucleotide
      polymorphism (SNP) loci of these two genes with several human diseases. 

PMID- 24082821
TI  - Understanding Molecular Mechanisms of Durable and Non-durable Resistance to
      Stripe Rust in Wheat Using a Transcriptomics Approach.
AB  - Stripe rust of wheat, caused by Puccinia striiformis f. sp. tritici, continues to
      cause severe damage worldwide. Durable resistance is necessary for sustainable
      control of the disease. High-temperature adult-plant (HTAP) resistance, which
      expresses when the weather becomes warm and plants grow older, has been
      demonstrated to be durable. We conducted numerous studies to understand the
      molecular mechanisms of different types of stripe rust resistance using a
      transcriptomics approach. Through comparing gene expression patterns with race
      specific, all-stage resistance controlled by various genes, we found that a
      greater diversity of genes is involved in HTAP resistance than in all-stage
      resistance. The genes involved in HTAP resistance are induced more slowly and
      their expression induction is less dramatic than genes involved in all-stage
      resistance. The high diversity of genes and less dramatic induction may explain
      durability and the incomplete expression level of HTAP resistance. Identification
      of transcripts may be helpful in identifying resistance controlled by different
      genes and in selecting better combinations of genes to combine for achieving
      adequate and durable resistance. 

PMID- 24082820
TI  - Integrated analysis of transcriptomic and proteomic data.
AB  - Until recently, understanding the regulatory behavior of cells has been pursued
      through independent analysis of the transcriptome or the proteome. Based on the
      central dogma, it was generally assumed that there exist a direct correspondence
      between mRNA transcripts and generated protein expressions. However, recent
      studies have shown that the correlation between mRNA and Protein expressions can
      be low due to various factors such as different half lives and post transcription
      machinery. Thus, a joint analysis of the transcriptomic and proteomic data can
      provide useful insights that may not be deciphered from individual analysis of
      mRNA or protein expressions. This article reviews the existing major approaches
      for joint analysis of transcriptomic and proteomic data. We categorize the
      different approaches into eight main categories based on the initial algorithm
      and final analysis goal. We further present analogies with other domains and
      discuss the existing research problems in this area. 

PMID- 24082822
TI  - In-Silico Algorithms for the Screening of Possible microRNA Binding Sites and
      Their Interactions.
AB  - MicroRNAs (miRNAs) comprise a recently discovered class of small, non-coding RNA
      molecules of 21-25 nucleotides in length that regulate the gene expression by
      base-pairing with the transcripts of their targets i.e. protein-coding genes,
      leading to down-regulation or repression of the target genes. However, target
      gene activation has also been described. miRNAs are involved in diverse
      regulatory pathways, including control of developmental timing, apoptosis, cell
      proliferation, cell differentiation, modulation of immune response to
      macrophages, and organ development and are associated with many diseases, such as
      cancer. Computational prediction of miRNA targets is much more challenging in
      animals than in plants, because animal miRNAs often perform imperfect base
      pairing with their target sites, unlike plant miRNAs which almost always bind
      their targets with near perfect complementarity. In the past years, a large
      number of target prediction programs and databases on experimentally validated
      information have been developed for animal miRNAs to fulfil the need of
      experimental scientists conducting miRNA research. In this review we first
      succinctly describe the prediction criteria (rules or principles) adapted by
      prediction algorithms to generate possible miRNA binding site interactions and
      introduce most relevant algorithms, and databases. We then summarize their
      applications with the help of some previously published studies. We further
      provide experimentally validated functional binding sites outside 3'-UTR region
      of target mRNAs and the resources which offer such predictions. Finally, the
      issue of experimental validation of miRNA binding sites will be briefly
      discussed. 

PMID- 24082823
TI  - Overview of Genomic Insights into Chicken Growth Traits Based on Genome-Wide
      Association Study and microRNA Regulation.
AB  - Over the two past decades, a significant number of studies have observed animal
      growth traits to examine animal genetic mechanisms due to their ease of
      measurement and high heritability. Chicken which has a significant impact on
      fundamental biology is a major source of protein worldwide, making it an ideal
      model for examining animal growth trait development. The genetic mechanisms of
      chicken growth traits have been studied using quantitative trait loci mapping
      through genome-scan and candidate gene approaches, genome-wide association
      studies (GWAS), comparative genomic strategies, microRNA (miRNA) regulation of
      growth development analysis, and epigenomic analysis. This review focuses on
      chicken GWAS and miRNA regulation of growth traits. Several recently published
      GWAS reports showed that most genome-wide significant single nucleotide
      polymorphisms are located on chromosomes 1 and 4 in chickens. Chicken growth,
      particularly skeletal muscle growth and development, is greatly regulated by
      miRNA. Using dwarf and normal chickens, let-7b was found to be involved in
      determining chicken dwarf phenotypes by regulating growth hormone receptor gene
      expression. 

PMID- 24082824
TI  - Role of the Transforming-Growth-Factor-beta1 Gene in Late-Onset Alzheimer's
      Disease: Implications for the Treatment.
AB  - Late-onset Alzheimer's disease (LOAD) is the most common form of dementia in the
      elderly. LOAD has a complex and largely unknown etiology with strong genetic
      determinants. Genetics of LOAD is known to involve several genetic risk factors
      among which the Apolipoprotein E (APOE) gene seems to be the major recognized
      genetic determinant. Recent efforts have been made to identify other genetic
      factors involved in the pathophysiology of LOAD such as genes associated with a
      deficit of neurotrophic factors in the AD brain. Genetic variations of
      neurotrophic factors, such as brain-derived neurotrophic factor (BDNF), and
      transforming-growth-factor-beta1 (TGF-beta1) are known to increase the risk to
      develop LOAD and have also been related to depression susceptibility in LOAD.
      Transforming-Growth-Factor-beta1 (TGF-beta1) is a neurotrophic factor that exerts
      neuroprotective effects against beta-amyloid-induced neurodegeneration. Recent
      evidence suggests that a specific impairment in the signaling of TGF-beta is an
      early event in the pathogenesis of AD. TGF-beta1 protein levels are predominantly
      under genetic control, and the TGF-beta1 gene, located on chromosome 19q13.1-3,
      con-tains several single nucleotide polymorphisms (SNPs) upstream and in the
      transcript region, such as the SNP at codon +10 (T/C) and +25 (G/C), which is
      known to influence the level of expression of TGF-beta1. In the present review,
      we summarize the current literature on genetic risk factors for LOAD, focusing on
      the role of the TGF-beta1 gene, finally discussing the possible implications of
      these genetic studies for the selection of patients eligible for neuroprotective
      strategies in AD. 

PMID- 24082826
TI  - Effect of Hibiscus sabdariffa Calices on Dyslipidemia in Obese Adolescents: A
      Triple-masked Randomized Controlled Trial.
AB  - CONFLICT OF INTEREST: none declared. OBJECTIVE: We aimed to evaluate the effects
      of Hibiscus sabdariffa (HS) calices on controlling dyslipidemia in obese
      adolescents. METHODOLOGY: In this triple blind randomized placebo-controlled
      clinical trial which was registered in the Iranian registry for clinical trials
      (IRCT201109122306N2), 90 obese adolescents aged 12-18 years with documented
      dyslipidemia were randomly assigned in two groups of cases who received 2 grams
      of fine powdered calices of Hibiscus sabdariffa per day for one month and
      controls who received placebo powder with the same dietary and physical activity
      recommendations and duration of exposure. Full lipid profile and fasting blood
      sugar measured before and after the trial. Data were analyzed using multivariate
      general linear model. FINDINGS: Overall, 72 participants (mean age of 14.21+/
      1.6, 35 boys) completed the trial. The two arms of the study (cases and controls)
      were not statistically different in terms of age, gender, weight, body mass index
      (BMI) and lipid profile before the trial. Serum total cholesterol, low density
      lipoprotein cholesterol and serum triglyceride showed a significant decrease in
      cases group but high density lipoprotein cholesterol level was not changed
      significantly. CONCLUSION: It is concluded that Hibiscus sabdariffa calyces
      powder may have significant positive effects on lipid profile of adolescents
      which maybe attributed to its polyphenolic and antioxidant content. Further
      studies are needed on dose-response and formulation optimization.

PMID- 24082825
TI  - Unravelling the connection between metabolism and tumorigenesis through studies
      of the liver kinase B1 tumour suppressor.
AB  - The liver kinase B1 (LKB1) tumour suppressor functions as a master regulator of
      growth, metabolism and survival in cells, which is frequently mutated in sporadic
      human non-small cell lung and cervical cancers. LKB1 functions as a key upstream
      activator of the AMP-activated protein kinase (AMPK), a central metabolic switch
      found in all eukaryotes that govern glucose and lipid metabolism and autophagy in
      response to alterations in nutrients and intracellular energy levels. The
      LKB1/AMPK signalling pathway suppresses mammalian target of rapamycin complex 1
      (mTORC1), an essential regulator of cell growth in all eukaryotes that is
      deregulated in a majority of human cancers. LKB1 inactivation in cancer leads to
      both tumorigenesis and metabolic deregulation through the AMPK and mTORC1
      signalling axis and there remain critical challenges to elucidate the direct role
      LKB1 inactivation plays in driving aberrant metabolism and tumour growth. This
      review addresses past and current efforts to delineate the molecular mechanisms
      fueling metabolic deregulation and tumorigenesis following LKB1 inactivation as
      well as translational promise of therapeutic strategies aimed at targeting LKB1
      deficient tumors. 

PMID- 24082827
TI  - Prevention of diabetes in family medicine.
AB  - CONFLICT OF INTEREST: none declared. INTRODUCTION: The incidence of diabetes type
      2 (diabetes mellitus type 2 - DM 2) is rapidly increasing worldwide. Physical
      inactivity and obesity are the major determinants of the disease. Primary
      prevention of DM 2 entails health monitoring of people at risk category. People
      with impaired glycemic control are at high risk for development of DM 2 and enter
      the intensive supervision program for primary and secondary prevention. OBJECTIVE
      OF THE RESEARCH: To evaluate the impact of metformin and lifestyle modification
      on glycemia and obesity in patients with prediabetes. PATIENTS AND METHODS: The
      study was conducted on three groups of 20 patients each (total of 60 patients)
      aged from 45 to 80, with an abnormal glycoregulation and prediabetes. The study
      did not include patients who already met the diagnostic criteria for the
      diagnosis of diabetes. During the study period of 6 months, one group was
      extensively educated on changing lifestyle (healthy nutrition and increased
      physical activity), the second group was treated with 500 mg metformin twice a
      day, while the control group was advised about diet and physical activities but
      different from the first two groups. At beginning of the study, all patients were
      measured initial levels of blood glucose, HbA1C, BMI (Body Mass Index), body
      weight and height and waist size. Also the same measurements were taken at the
      end of the conducted research, 6 months later. For the assessment of diabetes
      control was conducted fasting plasma glucose (FPG) test and 2 hours after a
      glucose load, and HbA1C. RESULTS: At the beginning of the study the average HbA1C
      (%) values in three different groups according to the type of intervention
      (lifestyle changes, metformin, control group) were as follows: (6.4 +/- 0.5 mmol
      / l), (6.5 +/- 1.2 mmol / l), (6.7 +/- 0.5 mmol / l). At the end of the research,
      the average HbA1C values were: 6.2 +/- 0.3 mmol / l, 6.33 +/- 0.5 mmol / l and
      6.7 +/- 1.4 mmol / l. In the group of patients who received intensive training on
      changing lifestyle or group that was treated with metformin, the average
      reduction in blood glucose and HbA1C remained within the reference range and
      there were no criteria for the diagnosis of diabetes. Unlike the control group, a
      group that was well educated on changing habits decreased average body weight by
      4.25 kg, BMI by 1.3 and waist size by 2.5 cm. Metformin therapy led to a
      reduction in the average weight of 3.83 kg, BMI of 1.33 and 3.27 for waist size.
      Changing lifestyle (healthy diet and increased physical activity) has led to a
      reduction in total body weight in 60% of patients, BMI in 65% of patients,
      whereas metformin therapy led to a reduction of the total body weight in 50%, BMI
      in 45% of patients. In the control group, the overall reduction in body weight
      was observed in 25%, and BMI in 15% of patients. CONCLUSION: Modification of
      lifestyle, such as diet and increased physical activity or use of metformin may
      improve glycemic regulation, reduce obesity and prevent or delay the onset of
      developing DM 2.

PMID- 24082828
TI  - Stroke emergency medical care: initial assessment, risk factors, triage and
      hospitalization outcome.
AB  - CONFLICT OF INTEREST: none declared. GOALS: THE GOALS OF THIS RESEARCH ARE: a) to
      determine the number, gender and age representation of patients with a working
      diagnosis of acute stroke referred by the Institute for Emergency Medical Care
      (IEMC) in the Clinical Center of Sarajevo University (CCSU); b) determine the
      incidence of patients that have been or have not been hospitalized and why; c)
      determine the time and procedure for emergency medical care; d) to determine the
      characteristics and outcomes of patients hospitalized with ischemic stroke at the
      Neurology Clinic CCUS. MATERIAL AND METHODS: The study was retrospective and
      included time period from 1st June 2010 to 30th November 2010. The study included
      patients of both sexes, older than 18 years of age. RESULTS: The study included a
      total of 233 patients. Of these, 65% are female, while 35% of patients were male.
      Of 82 patients who were admitted to hospital treatment at the Neurology Clinic,
      55% of the patients were male and 45% female. The largest number of patients is
      older than 70 years (71%). Minimum time for emergency medical team arrival was 6
      minutes and maximum 70 minutes (mean 35, SD 11.989). Motor weakness was noted in
      31% of patients - left sided motor weakness was significantly more represented.
      In 73% of patients the diagnosis was confirmed. In 5% of patients thrombolytic
      therapy was administered, while 95% of patients were treated conservatively.
      Lethal outcome occurred in 30% of hospitalized patients, 37% were discharged as
      recovered, 30% were discharged as unaltered state, while 3% were discharged with
      worsening symptoms. Among risk factors, hypertension is the leading one, followed
      by an earlier stroke, diabetes mellitus, and cardiac arrhythmias. CONCLUSIONS: In
      91% of patients consciousness was preserved. In 73% of transported patients has
      been confirmed the diagnosis of ischemic stroke. Of the patients with confirmed
      diagnosis 59% were hospitalized. A significant number of strokes occur for the
      first time in relation to relapse. 5% of patients were treated with thrombolysis,
      while others were treated with conservative therapy. Recurrent stroke and patient
      confusion have significant impact on the outcome.

PMID- 24082829
TI  - The Changes of Pulmonary Function in COPD During Four-Year Period.
AB  - CONFLICT OF INTEREST: none declared. INTRODUCTION: COPD (chronic obstructive
      pulmonary disease) is characterized by airflow limitation that is not fully
      reversible. OBJECTIVE: to show the changes of pulmonary function in COPD during
      the 4 -year evolution of illness. MATERIAL AND METHODS: The research was done on
      patients suffering from COPD treated at the Clinic "Podhrastovi" during 2006 and
      2007. The tested parameters were examined from the date of receiving patient with
      COPD to hospital treatment in 2006 and 2007 and then followed prospectively until
      2010 or 2011 (the follow-up period was 4 years). There were total 199 treated
      patients who were chosen at random and regularly attended the control
      examinations. The study was conducted on adult patients of both sexes, different
      age group. In each patient the duration of illness was recorded so is sex, age,
      data of smoking habits, information about the regularity of taking bronchodilator
      therapy during remissions of disease, about the treatment of disease
      exacerbations, results of pulmonary functional tests as follows: FVC (forced
      vital capacity), FEV1 (forced expiratory volume in one second) and bronchodilator
      reversibility testing. All these parameters were measured at the beginning and at
      the end of each hospital treatment on the apparatuses of Clinic "Podhrastovi". We
      took in elaboration those data obtained in the beginning of the first
      hospitalization and at the end of the last hospitalization or at the last control
      in outpatient department when patient was in stable state. Patients were divided
      into three groups according to the number of exacerbations per year. RESULTS:
      airflow limitation in COPD is progressive; both FVC and FEV1 shows the
      statistically significant decrease during follow-up period of 4 years (p values /
      for both parameters/ =0.05) . But in patients regularly treated in phases of
      remission and exacerbations of illness the course of illness is slower. The fall
      of FVC and FEV1 is statistically significantly smaller in those received regular
      treatment in phases of remissions and exacerbations of illness (p values / for
      both parameters/ =0.01). The number of patients responding properly to
      bronchodilators decreased statistically significantly in patients with COPD
      during follow-up period (p=0.05). CONCLUSION: COPD is characterized with airflow
      limitation which is progressive in the course of illness, but that course may be
      made slower using appropriate treatment during remission and exacerbations of
      diseases.

PMID- 24082830
TI  - Behavior of young people regarding family planning.
AB  - CONFLICT OF INTEREST: none declared. Family planning is a conscious activity of
      reproductive age that inclines, not only to regulate the number and timing of
      birth, but also to have a healthy child and to fulfill all of its role throughout
      the life cycle. The survey included 1804 students of various generations, which
      is approximately 9.3% of all students of the University of Montenegro. Instrument
      of survey was questionnaire with 25 closed type questions. Methods used for
      statistical data analyses were methods of descriptive statistics and
      nonparametric methods to analyze significance of differences at the significance
      p>0.05. The study comprised 53.9% of students aged up to 20 years and 46.1% of
      students aged from 21 to 26 years. There is statistically significant difference
      among students regarding sources of knowledge on family planning by age (Chi 2 =
      14.54, p<0.05). The students have got information on family planning mostly from
      parents (46.7%). Out of total number of interviewed students, who stated that
      abortion is good method of contraception, 12.8% claimed doctors as the source of
      information, then books, mass media and parents. The most of interviewed students
      find condom as the best contraceptive method. Students used to get information on
      family planning mostly often from their parents, and most of them consider that
      they are well informed. One third of students do not protect themselves from
      undesired pregnancy, but most of them consider abortion as non adequate method of
      family planning.

PMID- 24082831
TI  - Epidemiology of rheumatoid arthritis in tirana, Albania.
AB  - CONFLICT OF INTEREST: none declared. AIM: Rheumatoid arthritis is considered a
      clinical syndrome across several disease subsets characterized by systemic
      inflammation, persistent synovitis, and autoantibodies. Our aim was to assess the
      distribution of risk factors among people diagnosed with rheumatoid arthritis in
      the adult population of Tirana, the capital city of Albania. METHODS: All
      individuals diagnosed with rheumatoid arthritis in primary health care services
      of Tirana city during the period 2009-2012 were included in this study. The
      diagnosis of rheumatoid arthritis was based on the clinical signs and symptoms
      and laboratory tests including measurement of the rheumatoid factor. RESULTS:
      Overall, there were identified 817 cases with rheumatoid arthritis in all primary
      health care centers of Tirana for the period 2009-2012. Of these, 529 (65%) were
      women and 288 (35%) were men. Genetic factors accounted for 60% of the diseases
      in women and 45% in men (P<0.001). In both sexes, the proportion of older
      individuals was higher compared with younger adults. Most of the individuals with
      rheumatoid were from urban areas of Tirana. CONCLUSION: Our study provides new
      evidence about the distribution of risk factors of rheumatoid arthritis in
      transitional Albania where valid and reliable data about this disease were
      scarce. Future studies in Albania should assess the prevalence of rheumatoid
      arthritis in population-based samples.

PMID- 24082832
TI  - Phytoestrogens impact on menopausal symptomatology.
AB  - CONFLICT OF INTEREST: none declared. INTRODUCTION: The balance of endocrine and
      autocrine activity usually starts to fade after age of 45 years in women. This is
      particularly true for the imbalance of estrogen and progesterone. This imbalance
      creates a number of clinical syndromes and disorders. GOAL: The goal of the study
      is to determine the effects of phytoestrogens on the psychological, somatic
      vegetative and urogenital symptoms of menopause. MATERIAL AND METHODS: The study
      included 275 respondents who are more than three in menopause. Respondents were
      taking commercially available phytoestrogens, in duration of 12 months. RESULTS
      AND DISCUSSION: Review of clinical and epidemiological studies showing different
      results regarding effects of phytoestrogens on menopausal symptoms. In our study
      there was a significant reduction of somatic-vegetative and psychological
      symptoms under the influence of phytoestrogens, while urogenital symptomatology
      was not significantly changed. We recommend the use of phytoestrogens in early
      postmenopausal women with moderate symptoms.

PMID- 24082833
TI  - Congenital blindness and visual impairment cause infection or non infection.
AB  - CONFLICT OF INTEREST: none declared. INTRODUCTION: Authors are from reference
      documentation to archive at Organization of Federation of blind and visually
      impaired in central Serbia (Kragujevac), by retrograde analysis, of 2007-2012,
      comprehend two groups by etiology-clinical characteristics of congenital
      blindness and visually impaired, caused infection or non infection example. AIM:
      to analyze relationship between infectious and non infectious of congenital
      blindness and visually impaired in our referent region and compare with world
      references. MATERIAL/METHODS: With 6-years analysis included the most frequency
      cases of congenital blindness and visually impaired in two groups, according to
      presence or absence infectious causes. From infectious causes of congenital
      blindness and visually impaired are included: CMV - infection, congenital rubella
      syndrome, congenital toxoplasmosis, congenital syphilis and rare mixed syndrome.
      From non infectious causes are included: retinitis pigmentosa, retinopathy
      prematurity, primary congenital glaucoma, Leber's congenital amaurosis and rare
      syndrome. RESULTS: From total number of registered blind and visually impaired -
      1308 (100%), over the last 6 years, the registration was 349 (26.68%) with
      congenital blindness and visually impaired. From recorder with the number of the
      most common congenital blindness and visually impaired-194 (55.59%) with
      infections cause, and 155 (44.41%) non infection cause. CONCLUSION: Congenital
      blindness has shown permanent increase in past 6 years, in group with infectious
      and with non infectious causes. Congenital blindness and visually impaired of the
      most common etiology among registered members of our association in Kragujevac is
      subject of our correlation and global trends mentioned observation of these
      diseases.

PMID- 24082834
TI  - Characteristics of travellers from bosnia and herzegovina to Africa.
AB  - CONFLICT OF INTEREST: none declared. INTRODUCTION: Travellers from Bosnia and
      Herzegovina (B&H) travel to different world countries. The awareness of people is
      changing every day and nowadays travellers seek advices related to their travel
      and destination more often than before. In the previous years, travellers came to
      Travel Clinics almost only to get the vaccines which were obligatory for entry
      into a country. In B&H travel clinics are a part of public health institutes. The
      largest Travel Clinic which provides service for the highest number of travellers
      is in the Public Health Institute of Sarajevo Canton, in the city of Sarajevo,
      which is the capital of B&H. In the last years we have seen an increasing
      interest for travel to Africa because the highest number of travellers travel to
      African countries. OBJECTIVE: To show the characteristics of persons travelling
      to Africa, the reasons of their travel, the destination countries and the types
      of vaccines applied. MATERIALS AND METHODS: We used protocol books of the Travel
      Clinic in Public Health Institute of Sarajevo Canton and the data from individual
      forms of travellers. RESULTS: Persons travelling to Africa make 55% of all
      travellers that are advised and vaccinated in the Travel Clinic in Public Health
      Institute of Sarajevo Canton. There are significantly more men than women among
      people travelling to Africa. The highest number of travellers is in the category
      of working population which means age group of 20-50 years. The most visited
      countries are Kenya, Ethiopia, Somalia and Ghana. Travellers received the
      following vaccines: yellow fever, VHA, VHB, meningitis, tetanus. All travellers
      were given the advice on how to dress, feed and protect against malaria.

PMID- 24082835
TI  - Assessment of Reporting, Attitudes and Knowledge About the Stab Incidents and
      Professional Risk of Viral Infection among Health Care Professionals in Primary
      Health Care.
AB  - CONFLICT OF INTEREST: none declared. GOAL: The goal of the research is to
      determine the relationship between frequency and reporting of stab incidents,
      attitudes and knowledge about stab incidents and occupational risk for
      transmission of viral infection with HBV, HCV or HIV among health care
      professionals employed in primary health care. MATERIAL AND METHODS: Conducted is
      prospective, cross-section study by questionnaires in 2012. The survey included
      health professionals in Primary Health Care Center in Tuzla. The final sample has
      131 respondents (85% women). Statistical analysis was performed using the
      statistical package SPSS version 20.0. RESULTS: The prevalence rate of stab
      incidents throughout their career in our study was 66%; while the rate of
      reported incidents was 4.83 ~ 5 times lower than the actual prevalence. In 49 out
      of 87 cases this was a case of hollow needle prick. The most common causes of
      stab incidents are the time pressure, unforeseen reactions of patients and lack
      of concentration. CONCLUSION: Stab incidents are often not reported in in
      developing countries. Training in order to raise awareness and knowledge about
      the problem, proper procedures, good organization of work and anti-stress
      program, safer disposal, conducting prophylaxis before and after exposure
      monitored by the relevant institutions of occupational medicine should contribute
      to solving this problem.

PMID- 24082836
TI  - International Students of Isfahan University of Medical Sciences: A Survey about
      Their Needs and Difficulties.
AB  - CONFLICT OF INTEREST: none declared. INTRODUCTION: International students
      experience difficult situations in a foreign country that may intensify other
      problems, which are expected in these situations and may have harmful effects on
      the potential function of students. As the main problems of international
      students may vary in different situations, the aim of this study was to
      investigate the main problems of international students in Iran. METHODS: In this
      cross sectional survey, all international students in Isfahan University of
      Medical Sciences who were in Iran during 2006-2007 were evaluated by a
      questionnaire consisting of six scoops of educational, psychological, supporting
      communication, familial, economical and sociocultural. RESULTS: Problems referred
      to sociocultural scope had greater mean (2.44) followed by communication problems
      (2.30) and economical problems (2.16). CONCLUSION: We suggest that consulting
      centers should employ experts familiar with international students problems
      capable of communicating well with international students.

PMID- 24082837
TI  - Leadership, job satisfaction and organizational commitment in healthcare sector:
      proposing and testing a model.
AB  - CONFLICT OF INTEREST: none declared. INTRODUCTION: Employees' job satisfaction
      and commitment depends upon the leadership style of managers. This study
      clarifies further the relationships between leadership behaviors of managers and
      two employees' work-related attitudes-job satisfaction and organizational at
      public hospitals in Iran. A better understanding of these issues and their
      relationships can pinpoint better strategies for recruiting, promotion, and
      training of future hospital managers and employees, particularly in Iran but
      perhaps in other societies as well. METHODS: This cross-sectional study was
      conducted using self-administered questionnaires distributed among 814 hospital
      employees and managers through a stratified random sampling. RESULTS AND
      DISCUSSION: The dominant leadership style of hospital managers was participative
      style. Hospital employees were moderately satisfied with their jobs and committed
      to their organization. Salaries, benefits, promotion, contingent rewards,
      interpersonal relationships and working conditions were the best predictors of
      job satisfaction among hospitals employees. Leadership, job satisfaction and
      commitment were closely interrelated. The leadership behavior of managers
      explained 28% and 20% of the variations in job satisfaction and organizational
      commitment respectively. CONCLUSION: This study clarifies the causal relations of
      job satisfaction and commitment, and highlights the crucial role of leadership in
      employees' job satisfaction and commitment. Nevertheless, participative
      management is not always a good leadership style. Managers should select the best
      leadership style according to the organizational culture and employees'
      organizational maturity.

PMID- 24082838
TI  - Social Factors of Sickness Absences and the Significance of the Nature-culture
      Interplay in Coping.
AB  - CONFLICT OF INTEREST: none declared. AIMS: The aim of this study was to focus on
      and to discuss how social factors influence sickness absence. There were two aims
      of this study: a) To explore and reveal the absentees experiences and perceptions
      of sickness absence in daily life b) To explore and reveal the absentees own
      perceptions and experiences of coping while being on sickness absence. Methods.
      Qualitative method through a pragmatic synthesis of elements of ethnography and
      grounded theory were used. The sample from the county of Oppland, Norway (n=30)
      had a mental or a musculoskeletal diagnosis in accordance with the ICPC-2 medical
      classification system. Results. The interplay between working conditions and
      private life burdens has an impact on the development of illness and sickness
      absence, reinforcing the perception of a total life burden situation for women;
      including caring responsibilities. Men experience stress and conflicts at work,
      mostly from the leadership and its organizational structure. The majority of the
      sample used different techniques and strategies to cope with their illnesses,
      highlighting the significance of the nature-culture interplay. Conclusion. A
      holistic approach that considers the whole life situation must also be considered
      in order to understand gender differences in sickness absence. The importance of
      being involved in daily activities, and feelings of belonging to a social network
      were important for both men and women. This research may also add important
      awareness and understanding of Nature-Culture-Health (NaCuHeal) benefits in
      public health.

PMID- 24082839
TI  - Cytogenetic study in children with down syndrome among kosova Albanian population
      between 2000 and 2010.
AB  - CONFLICT OF INTEREST: none declared. AIM: The aim of this research was to
      ascertain the frequency of three basic cytogenetical types of Down syndrome among
      Kosova Albanian population and to evaluate the maternal age effect on the
      frequency of births of children with Down syndrome. METHODS: Cytogenetics
      diagnosis has been made according to the standard method of Moorhead and
      Seabright. RESULTS: In the time period 2000-2010 cytogenetics diagnosis of
      overall 305 children with Down syndrome has been realized. Of which in 285
      children (93.4%) were found free trisomy 21 (regular type), and in three other
      children (~1.0%) were detected mosaic trisomy 21. Translocation trisomy 21 was
      detected in 17 children (5.6%), of which in 14 children it occurred de novo
      translocation, whereas in 3 other children translocation has been inherited by a
      parent translocation carrier. The highest number of children with Trisomy 21 due
      to translocation was caused by Robertsonian translocation created by a fusion of
      two homologous chromosomes 21 (3.3%). Analysis showed that the number of children
      born with Down's syndrome, from 2000 to 2010, was not decreasing among the Kosova
      Albanian population. CONCLUSION: Down syndrome resulted by an extra free
      chromosome 21 is the most common genetic cause for that condition. Robertsonian
      translocations present in Down syndrome children often are de novo or inherited
      from a carrier parent with translocation.

PMID- 24082840
TI  - Monitoring and prevention of anemia relying on nutrition and environmental
      conditions in sports.
AB  - CONFLICT OF INTEREST: none declared. INTRODUCTION: Anemia is a blood disorder
      characterized by abnormally low levels of healthy red blood cells or reduced
      hemoglobin, the iron-bearing protein in red blood cells that delivers oxygen to
      tissues throughout the body. The most common symptoms of this disorder are
      fatigue, weakness and, in extreme cases, shortness of breath or palpitations, or
      you may have no symptoms at all. Sports anemia is a term loosely applied to a
      least three different conditions: hemodilution, iron deficiency anemia and foot
      strike anemia. Not exclusive to athletes, iron deficiency anemia occurs most
      often among women who may lose more iron each month when they menstruate than
      they take in. MATERIAL AND METHODS: Therefore, we examined its effect on the
      physical condition of female athletes. Several years (since 2010th until 2012th),
      we studied how anemia among girls (pioneers, juniors and seniors categories) that
      are involved in sports (women's soccer, volleyball and handball) in Rasina's
      district (Serbia), affecting their physical fitness. When their trainers approach
      to us, complaining that they have players who are great, so extraordinary
      talents, but by no means able to withstand more than twenty minutes in the game,
      we suggest them to perform laboratory tests. It was tested 134th female athletes.
      RESULTS AND DISCUSSION: Anemia was observed in 43. (9. pioneers, 19. juniors and
      15. seniors). So, laboratory results showed that in these girls anemia causes
      poor sport condition. After that, the girls enhanced nutrition. Their diet
      consisted of iron supplements and vitamins. Altitude training was organized for
      them, also. After all these treatments, condition significantly improved. It was
      first time that trainers in Rasina's district realizing significance of
      laboratory tests.

PMID- 24082841
TI  - Gender differences in living with diabetes mellitus.
AB  - CONFLICT OF INTEREST: none declared. The aim of this review is to discuss the
      gender difference among diabetic population. Metabolic control, age and gender
      significantly affect their psychosocial responses to disease. Psychosocial
      problems may also occur secondary to negative diabetes related experiences
      including diagnosis, increased stress and onset of complications. Although
      significant problems do not occur in all diabetic population, they occur in few
      patients. More work is needed in the area of identifying those patients having
      adjustment difficulties to diabetic related challenges. This review indicates
      that male diabetics are observed to be living more effectively with diabetes,
      lesser depression and anxiety but more energy and better positive wellbeing.

PMID- 24082842
TI  - Management of recurrent urinary tract infections in healthy adult women.
AB  - Recurrence after urinary tract infection (rUTI) is common in adult women. The
      majority of recurrences are believed to be reinfection from extraurinary sources
      such as the rectum or vagina. However, uropathogenic Escherichia coli are now
      known to invade urothelial cells and form quiescent intracellular bacterial
      reservoirs. Management of women with frequent symptomatic rUTI can be
      particularly vexing for both patients and their treating physicians. This review
      addresses available and promising management strategies for rUTI in healthy adult
      women. 

PMID- 24082843
TI  - Optimizing shock wave lithotripsy: a comprehensive review.
AB  - Shock wave lithotripsy is a commonly used procedure for eradicating upper urinary
      tract stones in patients who require treatment. A number of methods have been
      proposed to improve the results of this procedure, including proper patient
      selection, modifications in technique, adjunctive therapy to facilitate
      elimination of fragments, and changes in lithotripter design. This article
      assesses the utility of these measures through an analysis of contemporary
      literature. 

PMID- 24082844
TI  - Conservative treatment for postprostatectomy incontinence.
AB  - Postprostatectomy incontinence (PPI) is a bothersome complication of radical
      prostatectomy. Although most men recover from PPI, some men continue to have
      persistent urinary incontinence. The initial management of persistent PPI usually
      consists of conservative measures such as pelvic floor muscle exercises. Surgical
      treatments are usually not entertained for men with urinary incontinence until
      conservative treatments have failed. This article discusses risk factors for PPI
      and various options for its treatment, including biofeedback and pharmacotherapy.

PMID- 24082845
TI  - The use of vacuum erection devices in erectile dysfunction after radical
      prostatectomy.
AB  - The risk of postoperative erectile dysfunction (ED) following radical
      prostatectomy (RP) is reported to be between 14% and 89%. With an increase in the
      detection of prostate cancer in younger men, there is a greater emphasis on the
      appropriate management of ED following RP. A number of options are available to
      manage ED after RP, including phosphodiesterase-5 inhibitors, intracorporeal
      injections, intraurethral alprostadil, and vacuum erection devices (VEDs). Penile
      rehabilitation programs are increasingly used to facilitate the return of natural
      postoperative erections; the VED is an ideal therapy given that it increases
      blood flow and oxygenation to the corpora to reverse the changes that result in
      ED after RP. 

PMID- 24082846
TI  - Best of the 2013 AUA Annual Meeting: Highlights From the 2013 American Urological
      Association Meeting, May 4-8, 2013, San Diego, CA.

PMID- 24082847
TI  - Advances in localized prostate cancer: highlights from the 2012 friends of Israel
      urological symposium, july 3-5, 2012, tel aviv, Israel.

PMID- 24082848
TI  - Endoscopic management of genitourinary foreign bodies.
AB  - Retrieval of foreign bodies from the genitourinary system, most commonly inserted
      for sexual satisfaction or as a result of a psychiatric illness, can pose a
      significant surgical challenge. Due to their breadth of size, shape, and location
      within the genitourinary system, endoscopic management can be difficult. Here, we
      review the management of four cases of foreign object insertion into the
      genitourinary system and their outcomes and management. 

PMID- 24082849
TI  - Idiopathic granulomatous mastitis: an autoimmune disease?
AB  - PURPOSE: This study aimed to investigate the autoimmune basis of idiopathic
      granulomatous mastitis (IGM) by determining the anti-nuclear antibody (ANA) and
      extractable nuclear antigen (ENA) levels of patients diagnosed with IGM. MATERIAL
      AND METHODS: Twenty-six IGM patients were evaluated. Serum samples were analyzed
      for autoantibodies by indirect immunofluorescence (IIF) using a substrate kit
      that induced fluorescein-conjugated goat antibodies to human immunoglobulin G
      (IgG). IIF patterns were read at serum dilutions of 1 : 40 and 1 : 100 for ANA
      positivity. Using the immunoblot technique, the sera of patients were assayed at
      dilutions of 1 : 40 and 1 : 100 for human autoantibodies of the IgG class to 15
      lines of highly purified ENAs. RESULTS: In the IIF studies for ANA, positivity
      was identified for four different patterns in the 1 : 40 diluted preparations,
      for three different patients in the 1 : 100 diluted preparations and only one
      pattern was identified at the 1 : 320 dilution. In the ENA studies, positivity
      was identified for four different pattern in the 1 : 40 dilution, and only one
      pattern was identified at the 1 : 100 dilution. CONCLUSION: This study was not
      able to support the eventual existence of an autoimmune basis for IGM.

PMID- 24082851
TI  - Wind tunnel tests for wind pressure distribution on gable roof buildings.
AB  - Gable roof buildings are widely used in industrial buildings. Based on wind
      tunnel tests with rigid models, wind pressure distributions on gable roof
      buildings with different aspect ratios were measured simultaneously. Some
      characteristics of the measured wind pressure field on the surfaces of the models
      were analyzed, including mean wind pressure, fluctuating wind pressure, peak
      negative wind pressure, and characteristics of proper orthogonal decomposition
      results of the measured wind pressure field. The results show that extremely high
      local suctions often occur in the leading edges of longitudinal wall and windward
      roof, roof corner, and roof ridge which are the severe damaged locations under
      strong wind. The aspect ratio of building has a certain effect on the mean wind
      pressure coefficients, and the effect relates to wind attack angle. Compared with
      experimental results, the region division of roof corner and roof ridge from
      AIJ2004 is more reasonable than those from CECS102:2002 and MBMA2006.The
      contributions of the first several eigenvectors to the overall wind pressure
      distributions become much bigger. The investigation can offer some basic
      understanding for estimating wind load distribution on gable roof buildings and
      facilitate wind-resistant design of cladding components and their connections
      considering wind load path. 

PMID- 24082850
TI  - Antihyperlipidemic effects of Sesamum indicum L. in rabbits fed a high-fat diet.
AB  - The present study aimed to investigate the anti-hyperlipidemic effects of sesame
      in a high-fat fed rabbit model. Animals were randomly divided into four groups of
      eight animals each for 60 days as follows: normal diet, hypercholesterolemic diet
      (1% cholesterol), hypercholesterolemic diet (1% cholesterol) + sesame seed (10%),
      and hypercholesterolemic diet (1% cholesterol) + sesame oil (5%). Serum
      concentrations of total cholesterol, LDL-C, HDL-C, triglycerides, apoA and apoB,
      SGOT, SGPT, glucose and insulin were measured at the end of supplementation
      period in all studied groups. Hypercholesterolemic feeding resulted in a
      significant elevation of TC, TG, LDL-C, HDL-C, SGOT and SGPT as compared to the
      normocholesterolemic diet group (P < 0.05). Supplementation with sesame seed did
      not cause any significant alteration in lipid profile parameters,
      apolipoproteins, hepatic transaminases, glucose and insulin as compared to the
      hypercholesterolemic diet group (P > 0.05). In contrast, rabbits supplemented
      with sesame oil were found to have lower circulating concentrations of TC, LDL-C,
      HDL-C, SGOT and SGPT (P < 0.05), whilst concentrations of TG, apoA, apoB, insulin
      and glucose remained unaltered compared to the hypercholesterolemic diet group (P
      > 0.05). Supplementation with sesame oil, but not sesame seed, can ameliorate
      serum levels of lipids and hepatic enzymes in rabbits under a high-fat diet. 

PMID- 24082852
TI  - Emergy evaluation of a production and utilization process of irrigation water in
      China.
AB  - Sustainability evaluation of the process of water abstraction, distribution, and
      use for irrigation can contribute to the policy of decision making in irrigation
      development. Emergy theory and method are used to evaluate a pumping irrigation
      district in China. A corresponding framework for its emergy evaluation is
      proposed. Its emergy evaluation shows that water is the major component of inputs
      into the irrigation water production and utilization systems (24.7% and 47.9% of
      the total inputs, resp.) and that the transformities of irrigation water and rice
      as the systems' products (1.72E + 05 sej/J and 1.42E + 05 sej/J, resp.; sej/J =
      solar emjoules per joule) represent their different emergy efficiencies. The
      irrigated agriculture production subsystem has a higher sustainability than the
      irrigation water production subsystem and the integrated production system,
      according to several emergy indices: renewability ratio (%R), emergy yield ratio
      (EYR), emergy investment ratio (EIR), environmental load ratio (ELR), and
      environmental sustainability index (ESI). The results show that the performance
      of this irrigation district could be further improved by increasing the
      utilization efficiencies of the main inputs in both the production and
      utilization process of irrigation water. 

PMID- 24082853
TI  - Solving fuzzy fractional differential equations using Zadeh's extension
      principle.
AB  - We study a fuzzy fractional differential equation (FFDE) and present its solution
      using Zadeh's extension principle. The proposed study extends the case of fuzzy
      differential equations of integer order. We also propose a numerical method to
      approximate the solution of FFDEs. To solve nonlinear problems, the proposed
      numerical method is then incorporated into an unconstrained optimisation
      technique. Several numerical examples are provided. 

PMID- 24082854
TI  - Geotechnical characteristics and stability analysis of rock-soil aggregate slope
      at the Gushui Hydropower Station, southwest China.
AB  - Two important features of the high slopes at Gushui Hydropower Station are
      layered accumulations (rock-soil aggregate) and multilevel toppling failures of
      plate rock masses; the Gendakan slope is selected for case study in this paper.
      Geological processes of the layered accumulation of rock and soil particles are
      carried out by the movement of water flow; the main reasons for the toppling
      failure of plate rock masses are the increasing weight of the upper rock-soil
      aggregate and mountain erosion by river water. Indoor triaxial compression test
      results show that, the cohesion and friction angle of the rock-soil aggregate
      decreased with the increasing water content; the cohesion and the friction angle
      for natural rock-soil aggregate are 57.7 kPa and 31.3 degrees  and 26.1 kPa and
      29.1 degrees  for saturated rock-soil aggregate, respectively. The deformation
      and failure mechanism of the rock-soil aggregate slope is a progressive process,
      and local landslides will occur step by step. Three-dimensional limit equilibrium
      analysis results show that the minimum safety factor of Gendakan slope is 0.953
      when the rock-soil aggregate is saturated, and small scale of landslide will
      happen at the lower slope. 

PMID- 24082855
TI  - Mutations in MC1R gene determine black coat color phenotype in Chinese sheep.
AB  - The melanocortin receptor 1 (MC1R) plays a central role in regulation of animal
      coat color formation. In this study, we sequenced the complete coding region and
      parts of the 5'- and 3'-untranslated regions of the MC1R gene in Chinese sheep
      with completely white (Large-tailed Han sheep), black (Minxian Black-fur sheep),
      and brown coat colors (Kazakh Fat-Rumped sheep). The results showed five single
      nucleotide polymorphisms (SNPs): two non-synonymous mutations previously
      associated with coat color (c.218 T>A, p.73 Met>Lys. c.361 G>A, p.121 Asp>Asn)
      and three synonymous mutations (c.429 C>T, p.143 Tyr>Tyr; c.600 T>G, p.200
      Leu>Leu. c.735 C>T, p.245 Ile>Ile). Meanwhile, all mutations were detected in
      Minxian Black-fur sheep. However, the two nonsynonymous mutation sites were not
      in all studied breeds (Large-tailed Han, Small-tailed Han, Gansu Alpine Merino,
      and China Merino breeds), all of which are in white coat. A single haplotype
      AATGT (haplotype3) was uniquely associated with black coat color in Minxian Black
      fur breed (P = 9.72E - 72, chi-square test). The first and second A alleles in
      this haplotype 3 represent location at 218 and 361 positions, respectively. Our
      results suggest that the mutations of MC1R gene are associated with black coat
      color phenotype in Chinese sheep. 

PMID- 24082856
TI  - Autism in preschoolers: does individual clinician's first visit diagnosis agree
      with final comprehensive diagnosis?
AB  - Comprehensive clinical diagnosis based on all available information is considered
      the "gold standard" in autism spectrum disorders (ASD). We examined agreement
      across independent assessments (clinical judgment) of 34 young children (age 24
      46 months) with suspected ASD, assessed by a multidisciplinary team, and final
      comprehensive clinical diagnosis. Agreement across settings and between each
      clinician's assessment and final diagnosis was moderate. The poorest fit was
      found at assessment in connection with psychological evaluation and the best with
      preschool observation and parent interview. Some individual clinicians had good
      and others had poor fit with final diagnosis. Disagreement across assessments was
      pronounced for girls. The findings suggest that multidisciplinary assessments
      remain important and that comprehensive clinical diagnosis should still be
      regarded as the gold standard in ASD. 

PMID- 24082857
TI  - The antioxidant status and concentrations of coenzyme Q10 and vitamin E in
      metabolic syndrome.
AB  - The purpose of this study was to investigate the levels of coenzyme Q10 and
      vitamin E and the antioxidant status in subjects with metabolic syndrome (MS).
      Subjects with MS (n = 72) were included according to the criteria for MS. The non
      MS group (n = 105) was comprised of healthy individuals with normal blood
      biochemical values. The plasma coenzyme Q10, vitamin E concentrations, lipid
      profiles, and antioxidant enzymes levels (catalase, superoxide dismutase, and
      glutathione peroxidase) were measured. The subjects with MS had significantly
      higher concentrations of plasma coenzyme Q10 and vitamin E than those in the non
      MS group, but these differences were not significant after being normalized for
      triglyceride level. The levels of antioxidant enzymes were significantly lower in
      the MS group than in the non-MS group. The subjects with the higher antioxidant
      enzymes activities had significant reductions in the risk of MS (P < 0.01) after
      being adjusted for coenzyme Q10 and vitamin E. In conclusion, the subjects with
      MS might be under higher oxidative stress resulting in low levels of antioxidant
      enzyme activities. A higher level of antioxidant enzymes activities was
      significantly associated with a reduction in the risk of MS independent of the
      levels of coenzyme Q10 and vitamin E. 

PMID- 24082858
TI  - Association of nNOS gene polymorphism with ischemic stroke in Han Chinese of
      North China.
AB  - Nitric oxide (NO) is an important messenger molecule and effector molecule. This
      study aimed to investigate the relation of neuronal nitric oxide synthase (nNOS)
      gene polymorphism with ischemic stroke in Han Chinese of North China. This was a
      case-control study. A total of 413 patients with ischemic stroke were recruited
      from Han Chinese of North China. There were 201 males and 212 females. In
      addition, 477 healthy subjects served as controls including 224 males and 253
      females. Multiplex SNaPshot was employed to detect nNOS gene polymorphism
      (rs2293050, rs2139733, rs7308402, and rs1483757). Results showed that the
      rs1483757, rs2139733, and rs2293050 genotypes and allele frequencies were
      comparable between patients and controls. However, ischemic stroke patients had
      significantly reduced AG genotype and A allele frequency when compared with
      controls (P = 0.037, P = 0.041). After adjusting confounding factors (gender,
      age, smoking, history of drinking, hypertension, and diabetes), AG genotype and A
      allele were still related to ischemic stroke (OR = 0.572, 95% CI: 0.335-0.978, P
      = 0.041; OR = 0.611, 95% C: 0.378-0.985, and P = 0.041) and both were found to be
      protective factors. Our results showed that rs7308402 gene polymorphism of nNOS
      is related to ischemic stroke in Han Chinese of North China. 

PMID- 24082859
TI  - Current topics concerning joint preservation and minimally invasive surgery of
      the hip: editorial comment.

PMID- 24082860
TI  - The accuracy of the use of functional hip motions on localization of the center
      of the hip.
AB  - BACKGROUND: The hip joint is generally considered a ball-and-socket joint, the
      center of which is used as an anatomic landmark in functional analyses and by
      surgical navigation systems. The location of the hip center has been estimated
      using functional techniques using various limb motions. However, it is not clear
      which specific motions best predicted the functional center. PURPOSE: This study
      aims to compare the predicted functional center of the hip evaluated from
      multiplanar circumduction and star motions, and to compare this functional center
      with the geometric center. METHODS: Eight hips in four fresh-frozen cadavers were
      used and verified as morphologically normal in CT scans. Three-dimensional motion
      of each lower limb was recorded using arrays of reflective markers rigidly
      attached to the femur and pelvis. Each hip was manipulated to produce
      circumduction or star motion, i.e., abduction-adduction and flexion extension.
      The hip was then dissected and the bearing surface traced with a probe, from
      which a best-fit sphere was calculated. The functional center was calculated from
      the motion data and compared to the geometric technique. RESULTS: There was no
      difference between the functional hip center predicted by circumduction or star
      motions, although this was offset from the geometric hip center by up to 14 mm.
      For all except two hips, the functional center was less than 6 mm from the
      geometric hip in each anatomic direction. Test-retest differences were smaller
      for circumduction than for star motions. CONCLUSIONS: Estimation of the hip
      center based on motion of the femur relative to the pelvis could localize the
      geometric center of the joint within 14 mm and circumduction motions were more
      repeatable. CLINICAL RELEVANCE: Many surgical navigation systems make use of the
      functional hip center as a landmark for alignment or reconstruction. Errors
      associated with this would have a very minor influence in lower limb alignment,
      e.g., for knee reconstruction, but could affect proximal femoral geometry
      relevant to hip reconstruction.

PMID- 24082861
TI  - The development and validation of a more discriminating functional hip score for
      research.
AB  - BACKGROUND: Total hip arthroplasty (THA) is a commonly performed procedure with
      increasing frequency in the young adult. While most available outcome measures
      can document postoperative improvement in pain and function, they do not measure
      the ability to perform high-demand activities. QUESTIONS/PURPOSES: We present and
      validate a user-friendly discriminating hip scoring system (the functional hip
      score) for use in younger, "high-demand" patients undergoing hip arthroplasty
      surgery. METHODS: We studied 38 subjects without any hip symptoms and 72 patients
      undergoing THA for osteoarthritis of the hip. Preprocedure and postprocedure
      scores were collected in the latter cohort of patients. SF-36 and WOMAC scores
      were used to validate our functional scoring system. The functional hip score was
      tested for internal consistency, reliability, and criterion validity. RESULTS:
      The functional hip score had high test-retest reliability, internal consistency,
      and criterion validity. This can be used to measure functional outcome in the
      younger high-demand adult patient undergoing THA. CONCLUSION: Our discriminating
      functional hip score can reliably measure improvement in hip function in the
      younger high-demand adult. Current scoring systems have ceiling effects and are
      unable to differentiate a high performing hip replacement from the routine hip
      replacement. The use of functional tasks that are measured objectively allows
      better documentation of improvement in hip function.

PMID- 24082862
TI  - Finite Element Analysis Examining the Effects of Cam FAI on Hip Joint Mechanical
      Loading Using Subject-Specific Geometries During Standing and Maximum Squat.
AB  - BACKGROUND: Cam femoroacetabular impingement (FAI) can impose elevated mechanical
      loading in the hip, potentially leading to an eventual mechanical failure of the
      joint. Since in vivo data on the pathomechanisms of FAI are limited, it is still
      unclear how this deformity leads to osteoarthritis. PURPOSE: The purpose of this
      study was to examine the effects of cam FAI on hip joint mechanical loading using
      finite element analysis, by incorporating subject-specific geometries,
      kinematics, and kinetics. QUESTIONS: The research objectives were to address and
      determine: (1) if hips with cam FAI demonstrate higher maximum shear stresses, in
      comparison with control hips; (2) the magnitude of the peak maximum shear
      stresses; and (3) the locations of the peak maximum shear stresses. METHODS:
      Using finite element analysis, two patient models were control-matched and
      simulated during quasi-static positions from standing to squatting.
      Intersegmental hip forces, from a previous study, were applied to the subject
      specific hip geometries, segmented from CT data, to evaluate the maximum shear
      stresses on the acetabular cartilage and underlying bone. RESULTS: Peak maximum
      shear stresses were found at the anterosuperior region of the underlying bone
      during squatting. The peaks at the anterosuperior acetabulum were substantially
      higher for the patients (15.2 +/- 1.8 MPa) in comparison with the controls (4.5
      +/- 0.1 MPa). CONCLUSIONS: Peaks were not situated on the cartilage, but instead
      located on the underlying bone. The results correspond with the locations of
      initial cartilage degradation observed during surgical treatment and from MRI.
      CLINICAL RELEVANCE: These findings support the pathomechanism of cam FAI. Changes
      may originate from the underlying subchondral bone properties rather than direct
      shear stresses to the articular cartilage.

PMID- 24082864
TI  - Labral Resection or Preservation During FAI Treatment? A Systematic Review.
AB  - BACKGROUND: Open and arthroscopic treatment of femoroacetabular impingement and
      resultant labral pathology has increased significantly over the past decade.
      Although the functional importance of the labrum and the labral seal has been
      established in biomechanical studies, good clinical results have been reported
      for both labral debridement and labral refixation. QUESTIONS/PURPOSES: The
      purpose of this paper is to summarize existing literature on the surgical
      treatment of labral pathology to provide treatment recommendations and direct
      future research. A systematic review was performed with the following research
      question in mind: Does preservation of the hip labrum improve outcomes as
      compared to labral debridement for the treatment of labral pathology? METHODS:
      The MEDLINE database was searched for level I, II, or III articles in English or
      German comparing labral debridement to labral refixation. Five studies were
      included in the analysis. RESULTS: Good short-term results were reported for both
      groups. Three out of five papers report improved outcomes after labral refixation
      as compared to labral debridement. CONCLUSIONS: In short-term follow-up, labral
      refixation appears to have slightly better outcomes than labral debridement.
      Studies with prospectively defined cohorts and longer follow-up are, however,
      necessary to provide definitive recommendations for labral treatment.

PMID- 24082863
TI  - An algorithmic approach to mechanical hip pain.
AB  - BACKGROUND: As our understanding of hip pathology evolves, the focus is shifting
      toward earlier identification of hip pathology. Therefore, it is vitally
      important to elucidate intra-articular versus extra-articular pathology of hip
      pain in every step of the patient encounter: history, physical examination, and
      imaging. QUESTIONS/PURPOSES: The objective was to address the following research
      questions: (1) Can an algorithmic approach to physical examination of a painful
      non-arthritic hip provide a more accurate diagnosis and improved treatment plan?
      (2) Does an anatomical layered concept of clinical diagnosis improve diagnostic
      accuracy? (3) What are the diagnostic tools necessary for the accurate
      application of a four-layer (osteochondral, inert, contractile, and
      neuromechanical) diagnosis? METHODS: An unrestricted computerized search of
      MEDLINE was conducted. Different terms were used in various combinations.
      RESULTS: An algorithmic approach to physical examination of a painful
      nonarthritic hip, including history, physical examination (specific tests), and
      advanced imaging allow for better interpretation of debilitating intra- and extra
      articular disorders and their effect on core performance. Additionally, it
      improves our understanding as to how underlying abnormal joint mechanics may
      predispose the hip joint and the associated hemipelvis to asymmetric loads. These
      abnormal joint kinematics (layer I) can lead to cartilage and labral injury
      (layer II), as well as resultant injury to the musculotendinous (layer III) and
      neural structures (layer IV) about the hip joint and the hemipelvis. The layer
      concept is a systematic means of determining which structures about the hip are
      the source of hip pathology and how to best implement treatment. CONCLUSIONS: A
      clear understanding of the differential diagnosis of hip pain through a detailed
      and systematic physical examination, diagnostic imaging assessment, and the
      interpretation of how mechanical factors can result in such a wide range of
      compensatory injury patterns about the hip can facilitate the diagnosis and
      treatment recommendations.

PMID- 24082865
TI  - Caution Should be Taken in Performing Surgical Hip Dislocation for the Treatment
      of Femoroacetabular Impingement in Patients Over the Age of 40.
AB  - BACKGROUND: Open and arthroscopic procedures are treatment options for patients
      with femoroacetabular impingement (FAI). Age has been found to be a predictive
      factor in the outcome of patients undergoing periacetabular osteotomy (PAO) for
      hip dysplasia. It is unclear if older age contraindicates joint preservation
      through a surgical hip dislocation (SHD). QUESTIONS/PURPOSE: The purpose of this
      retrospective case series was to evaluate the short-term outcomes of patients
      over 40 years of age without radiographic evidence of end-stage arthritis who
      underwent SHD for the treatment of FAI and to determine whether older age should
      be a contraindication for joint-preserving procedures in these patients. Our
      specific aims included (1) documenting the intraoperative findings and
      procedures, (2) assessing pain relief provided, and (3) assessing treatment
      failures and postoperative complications, noting the number of patients that
      ultimately required total hip arthroplasty (THA). PATIENTS AND METHODS: All
      patients at age 40 and older who had SHD for the treatment of FAI were identified
      from a series of patients treated with SHD. Clinical notes, radiographs, and
      operative reports were reviewed to determine clinical results, complications, and
      the need for additional procedures. The minimum follow-up was 1 year (mean 3.9
      years; range 1-8 years). RESULTS: At final follow-up, 11/22 (50%) of hips had
      pain relief, while 11/22 (50%) either continued having significant symptoms or
      required THA. Five (23%) reported nontrochanteric pain symptoms that were the
      same or worse than before surgery, and six hips (27%) underwent subsequent THA).
      The average time between SHD and THA was 1.9 years (0.9-6.2). The average age of
      patients who went on to require THA was 45 (42-50) years. CONCLUSIONS: Surgical
      hip dislocation can be used for the treatment of FAI in patients over age 40, but
      strict selection criteria should be adhered to, as only half of the patients
      experienced significant improvement in their hip pain. THA was required in one
      third of hips for continued pain and radiographic progression of arthritis. SHD
      for treatment of pathology that is not amenable to hip arthroscopy should remain
      a surgical option in older patients with FAI only if joint degeneration is not
      present.

PMID- 24082866
TI  - Effect of pelvic osteotomy in the skeletally immature on acetabular coverage.
AB  - BACKGROUND: Although pelvic osteotomy in children has been effective in re
      establishing containment of the hip joint, its impact on hip joint development
      with respect to acetabular coverage is ill defined. PURPOSE: The purpose of this
      study is to determine the prevalence of acetabular overcoverage in patients who
      had pelvic osteotomy during childhood and its impact on patient function.
      PATIENTS AND METHODS: Between 1980 and 2008, all patients who had a pelvic
      osteotomy done at our institution for non-neuropathic hip dysplasia (DDH) or
      secondary to Legg-Calve-Perthes disease (LCP) prior to skeletal maturity were
      reviewed. A clinical assessment and the WOMAC, UCLA Activity Score, Marx activity
      score, and SF-36 quality-of-life questionnaires were completed. A standardized AP
      pelvic X-ray was performed to determine the acetabular coverage, signs of
      retroversion, and degenerative changes. RESULTS: Twenty-eight patients (32 hips)
      were identified, of which 14 (9 DDH, 5 LCP) agreed to participate. Impingement
      sign was positive in eight patients (six DDH, two LCP). Crossover and ischial
      spine signs were each present in ten hips. Tonnis grades were: 0 in 1 hip, 1 in
      10 hips, 2 in 2 hips, and 3 in 1 hip. The mean Tonnis angle was 11.6 +/- 8.6
      degrees . The mean CE angle was 24.0 +/- 15.9 degrees  with six hips having a CE
      angle <20 degrees  and one hip with a CE angle >40 degrees . There was no
      correlation between crossover sign or ischial sign and Tonnis grade (p = 0.739),
      hip pain (p = 0.520), or impingement sign (p = 1.00). CONCLUSIONS: Acetabular
      overcoverage is common in patients who underwent pelvic osteotomy during
      childhood. No correlation was identified between retroversion and hip pain in our
      patient cohort.

PMID- 24082867
TI  - Labral refixation: current techniques and indications.
AB  - BACKGROUND: Labral tears have been associated with femoroacetabular impingement,
      instability, sports-related activity or trauma, capsular laxity or hypermobility,
      dysplasia, and degeneration. Disruption of the labrum increases the rate of
      acetabular cartilage compression and the contact stress between the femoral and
      acetabular cartilage. If left untreated, these lesions will alter normal hip
      joint function and may eventually lead to osteoarthritis. METHODS: For the labrum
      with adequate tissue (>7 mm), the labrum is repaired if it is detached or torn.
      If the labrum is bruised, a rim reduction and repair is performed, especially in
      the presence of cartilage damage and the labral-chondral junction. Labri are
      debrided only if there is enough substance to maintain the function of the
      labrum. Care must be taken to fix the labrum so that it provides adequate seal
      with the femoral head. RESULTS: Two-year outcome on 122 patients who underwent
      arthroscopic treatment for femoroacetabular impingement and chondrolabral
      dysfunction showed that, overall, most patients showed an improvement in symptoms
      and function and were satisfied with the results. Independent predictors of
      improved outcomes were joint space >2 mm and repair of labral pathology instead
      of debridement. Several other studies have shown excellent results following
      labral refixation and repair. CONCLUSIONS: Labral tears have been associated with
      femoroacetabular impingement, instability, sports-related activity or trauma,
      capsular laxity or hypermobility, dysplasia, and degeneration. Untreated labral
      tears can result in premature osteoarthritis of the hip. Debridement only used to
      be the standard of care, but excellent results reveal arthroscopic labral repair
      and refixation are an option with good outcomes.

PMID- 24082868
TI  - Is it Time for Cementless Hip Resurfacing?
AB  - BACKGROUND: Metal-on-metal bearing with cemented femoral component and cementless
      acetabular fixation is the current standard in surface replacement arthroplasty
      (RSA) of the hip. Because of concerns about the long-term survivorship of
      cemented stems in conventional hip arthroplasty, it seems logical to achieve
      cementless fixation on the femoral side with RSA. QUESTIONS/PURPOSES: The goals
      of this review were to evaluate clinical and radiological data reported from
      previously published cementless RSA series. In addition, we intend to review
      author's preliminary experience with Conserve Plus cementless devices
      specifically assessing the clinical outcomes, the complications rate, the
      survivorship, and the metallic ions levels measured in follow-up. METHODS: A
      references search was done with PubMed using the key words "cementless hip
      resurfacing", "cementless hip resurfacing prosthesis", and "femoral cementless
      hip resurfacing". Additionally, the clinical outcomes, the complications rate,
      the survivorship, and the metallic ions levels were measured in 94 cementless
      Conserve Plus((c)) devices in 90 patients (68 males and 22 females) with a mean
      age of 41.1 years (18-59). Mean follow-up was 13.1 months (8-16). RESULTS: No
      revision was performed during the observed follow-up. Neither radiological signs
      of loosening nor neck narrowing >10% were evident. Chromium and cobalt levels in
      whole blood samples rose respectively from 0.53 MUg/l (0.1-1.7) to 1.7 MUg/l (0.6
      2.9) and from 0.54 MUg/l (0.1-1.4) to 1.98 MUg/l (0.1-2.8). CONCLUSIONS:
      Cementless "fit and fill" femoral-side fixation, which seems to be potentially
      evolved and design-related, should be considered for future hip-resurfacing
      device generations.

PMID- 24082869
TI  - Groin pain after metal on metal hip resurfacing: mid-term follow-up of a
      prospective cohort of patients.
AB  - BACKGROUND AND PURPOSE: Groin pain after metal on metal hip resurfacing has been
      previously reported. The purpose of this study was to determine the natural
      history of a cohort of patients with groin pain after hip resurfacing previously
      reported on and incidence of revision surgery. METHODS: Our group previously
      reported an 18% incidence of groin pain at a mean of 18 months post hip
      resurfacing. This cohort of groin pain patients was prospectively followed.
      Patients were evaluated using a visual analog pain rating score, the University
      of California at Los Angeles (UCLA) Physical Activity Index, and the Western
      Ontario and McMaster Universities Osteoarthritis (WOMAC) Index. Functional
      outcome scores were compared from initial to latest follow up using the paired
      Student's t test. Further diagnostic evaluation and/or intervention or other
      complication was also recorded. RESULTS: The latest mean follow up from surgery
      was 63 +/- 15 months. The mean pain rating, UCLA, and WOMAC scores all improved
      at latest follow up, although WOMAC score improvement was not statistically
      significant. Mean pain rating score improved from 5.2 +/- 2.0 to 2.5 +/- 1.4 (p =
      0.0001). UCLA activity score improved from 6.4 +/- 2.0 to 6.9 +/- 1.6 (p = 0.03).
      Total WOMAC score improved from 75.6 +/- 20.5 to 84.5 +/- 14.8 (p = 0.15). Only
      one patient was revised for an adverse local tissue reaction. CONCLUSION: Groin
      pain post hip resurfacing has a multifactorial etiology, and in the vast majority
      of cases improves over time with no significant functional limitations. However,
      the surgeon should be aware of the many potential causes, and help minimize the
      possibility with proper patient selection and surgical technique.

PMID- 24082870
TI  - Metal-on-Metal Bearing: Is This the End of the Line? We Do Not Think So.
AB  - BACKGROUND: Recent studies have recommended the discontinuation of metal-on-metal
      (MoM) components in total hip arthroplasty (THA) because of adverse effects
      reported with large-diameter MoM THA. This is despite favorable long-term results
      observed with 28 and 32 mm MoM bearings. QUESTIONS/PURPOSES: The aim of this
      study was to assess the value of calls for an end to MoM bearings as THA
      components. Specifically, we wish to address the risks associated with MoM
      bearings including adverse soft tissue reactions, metal ion release, and
      carcinogenic risk. METHODS: The study evaluates the arguments in the literature
      reporting on MoM (adverse soft tissue reactions, metal ion release, and
      carcinogenic risk) and the experience of the current authors who re-introduced
      these bearings in 1995. They are balanced by a benefit-risk review of the
      literature and the authors' experience with MoM use. RESULTS: Adverse reactions
      to metallic debris as well as metal ion release are predictable and can be
      prevented by adequate design (arc of coverage, clearance), metallurgy (forged
      instead of cast alloy, high-carbide content), and appropriate component
      orientation. There is no scientific evidence that carcinogenicity is increased in
      subjects with MoM hip prostheses. MoM articulations appear to be attractive
      allowing safe hip resurfacing, decreasing the risk of THA revision in active
      patients, and providing secure THA fixation with cement in cages in severely
      deformed hips. MoM bearings in women of child-bearing age are controversial, but
      long-term data on metallic devices in adolescents undergoing spinal surgery seem
      reassuring. DISCUSSION: Adequate selection of MoM articulations ensures their
      safe use. These articulations are sensitive to orientation. Fifteen years of safe
      experience with 28- and 32-mm bearings of forged alloy and high-carbide content
      is the main reason for retaining them in primary and revision THA.

PMID- 24082871
TI  - Ideal femoral head size in total hip arthroplasty balances stability and
      volumetric wear.
AB  - BACKGROUND: Over the last several years, a trend towards increasing femoral head
      size in total hip arthroplasty to improve stability and impingement free range of
      motion has been observed. PURPOSE: The specific questions we sought to answer in
      our review were: (1) What are the potential advantages and disadvantages of metal
      on-metal, ceramic-on-ceramic, and metal-on-polyethylene bearings? (2) What is
      effect that femoral head size has on joint kinematics? (3) What is the effect
      that large femoral heads have on bearing surface wear? METHODS: A PubMed search
      and a review of 2012 Orthopaedic Research Society abstracts was performed and
      articles were chosen that directly answered components of the specific aims and
      that reported outcomes with contemporary implant designs or materials. RESULTS: A
      review of the literature suggests that increasing femoral head size decreases the
      risk of postoperative dislocation and improves impingement free range of motion;
      however, volumetric wear increases with large femoral heads on polyethylene and
      increases corrosion of the stem in large metal-on-metal modular total hip
      arthroplasty (THA); however, the risk of potentially developing osteolysis or
      adverse reactions to metal debris respectively is still unknown. Further, the
      effect of large femoral heads with ceramic-on-ceramic THA is unclear, due to
      limited availability and published data. CONCLUSIONS: Surgeons must balance the
      benefits of larger head size with the increased risk of volumetric wear when
      determining the appropriate head size for a given patient.

PMID- 24082872
TI  - Hip resurfacing: a 40-year perspective.
AB  - BACKGROUND: Saving bone by resurfacing the femoral head is not a new concept and
      the appeal for this type of hip replacement has remained despite the difficulties
      to find a bearing material suitable for this procedure. PURPOSE: In this article,
      the unique experience of a surgeon who has been performing hip resurfacing since
      its early development is presented, along with a comparative analysis of the
      performance of successive designs. RESULTS: The overall 10-year Kaplan-Meier
      survivorship of the early designs with polyethylene bearings did not exceed 62%
      while that of the current Conserve(r)Plus metal-on-metal hybrid design implanted
      with second generation surgical technique is in excess of 92%. Further
      exceptional, in the 10-year survivorship, 99.7% has been achieved with femoral
      size of 46 mm and good bone quality. Cementless acetabular components provide
      better enduring fixation than cemented designs. DISCUSSION: Metal-on-metal is
      currently and fortunately the only highly successful bearing material that can
      combine low wear rates and the manufacturing of a thin acetabular component to
      preserve bone and still accommodate the large femoral head of a hip resurfacing.
      The adverse local tissue reactions (ALTR) associated with metal-on-metal devices
      are not a bearing material issue per se but one of the device design and surgical
      technique. Almost all of ALTR and the rare events of systemic toxicity are due to
      abnormal wear patterns which can be prevented by proper acetabular component
      design and precise socket orientation in both the coronal and sagittal planes.
      Further improvements of the long-term durability with hip resurfacing can be
      anticipated with the use of recently developed trabecular bone-like tantalum or
      titanium porous coatings and with proper training of the surgeons interested in
      performing hip resurfacing arthroplasty.

PMID- 24082873
TI  - Adoption of hip resurfacing arthroplasty at hospital for special surgery: a
      cohort study.
AB  - BACKGROUND: Hip resurfacing arthroplasty (HRA) is an alternative to traditional
      total hip replacement (THR) that allows for the preservation of femoral bone. It
      is a more technically difficult procedure that has led some researchers to report
      an unsatisfactory learning curve (Berend et al., J Bone Joint Surg Am Suppl 2:89
      92, 2011; Mont et al., Clin Orthop Relat Res 465:63-70, 2007). PURPOSE: The
      purpose of this study was to investigate the adoption of HRA at our institution,
      examining the clinical results, revision rate, and modes of failure.
      Additionally, a comparison of three different implant systems was performed.
      METHODS: A retrospective review of a consecutive series of HRA performed at our
      institution between the years 2004 and 2009 was carried out. A total of 820 HRA
      with a minimum of 2 years of follow-up were included in the study. The majority
      of included patients were males (70%), with osteoarthritis (92%). The average age
      was 49.8 years, and the mean BMI was 27.5 kg/m(2). RESULTS: The average Harris
      hip score improved from 61 to 96.5 postoperatively. Thirteen revisions (1.6%)
      were performed for femoral neck fracture, femoral head osteonecrosis, acetabular
      loosening, metal reactivity/metallosis, and metal allergy. The overall Kaplan
      Meier survival curve with revision surgery as an endpoint showed 98.5% survival
      at 5 years. There were no observable differences in clinical scores or revision
      rates between the different implant systems. CONCLUSIONS: HRA can be successfully
      adopted with a low complication rate, given careful patient selection,
      specialized surgical training, and use of good implant design.

PMID- 24082874
TI  - Ceramic-Ceramic Bearing: Too Unpredictable to Use it Regularly.
AB  - BACKGROUND: Ceramic-on-ceramic (CoC) bearings have excellent tribologic
      properties because of the smoothness, hardness, and wettability of the material.
      Therefore, their use has been proposed in younger, active patients who may wear
      out a traditional metal-on-polyethylene bearing. The same material properties
      that are beneficial to tribology may also create problems, however. For example,
      squeaking and fracture of the bearing materials have been reported to occur.
      PURPOSE: The purpose of this paper was to investigate the literature reporting
      the complications of ceramic bearings and attempt to provide insight into their
      implications. METHODS: The US National Library of Medicine Database (PubMed) was
      searched using the terms "ceramic-ceramic total hip replacement,"
      "complications," "squeaking," and "fracture." Only clinical studies with a clear
      reporting of the incidence of these complications were included. RESULTS: The
      literature reports that squeaking of the CoC bearing occurs in a certain
      percentage of patients and is likely indicative of edge loading and excessive
      wear. Other factors, such as patient height, weight, range of motion, and implant
      design, may contribute to the propensity for squeaking. Fracture is a unique risk
      of the CoC articulation that requires revision surgery. Though improvements in
      manufacturing techniques have reduced the fracture risk to a very low percentage,
      the ceramic material remains susceptible to this complication by impingement and
      component malposition. CONCLUSIONS: Because of these possible negative outcomes
      associated with the ceramic material, the CoC bearing is too unpredictable to use
      regularly, and its use should be limited to patients who would benefit the most
      from it.

PMID- 24082875
TI  - A mid-term analysis suggests ceramic on ceramic hip arthroplasty is durable with
      minimal wear and low risk of squeak.
AB  - BACKGROUND: The incidence of hip replacements in the younger patient is ever
      increasing. With this in mind, improving the longevity of hip arthroplasties is
      paramount. Alumina ceramic is a promising bearing surface due to its low wear
      rate and biological inertness. PURPOSE: This study aims to review our experience
      with ceramic-on-ceramic total hip arthroplasty, reporting on the need for
      revision as well as the cause of failure. Our secondary purpose is to review our
      experience with the phenomenon of squeaking analysing and its effect on clinical
      outcome with specific emphasis on component positioning. Also reported are the
      results of our retrieval analysis of explanted components documenting the wear
      rate and our analysis of strip wear. METHODS: A consecutive series of 301 primary
      cementless alumina-on-alumina total hip arthroplasties at a minimum of 10 years
      follow-up was reviewed. These arthroplasties all had third-generation ceramic-on
      ceramic bearings performed through a posterior approach with repair of capsule
      and external rotators to bone. We analysed hips both clinically and
      radiographically. Analysis of wear in 62 ceramic bearings was performed using a
      Roundtest RA300 machine (Mitutoyo; Andover, UK), which has an accuracy of 0.01
      MUm. RESULTS: Overall, the survival rate of the implants was 98% at 10 years. No
      ceramic fractures were encountered in this study. Seventy-four patients reported
      squeaking hips, and two cases were revised due to squeaking (0.6%). No failures
      were related to bearing wear. CONCLUSIONS: We believe that ceramic-on-ceramic is
      a safe bearing coupling with excellent survivorship at 10 years.

PMID- 24082876
TI  - Neck-preserving femoral stems.
AB  - BACKGROUND: Surgeons undertaking total hip arthroplasty (THA) routinely perform a
      distal femoral neck resection. It has been argued that retaining the femoral neck
      during THA can provide mechanical and biological advantages. PURPOSES: The
      objectives of this study were to review: (1) the current evidence on the
      advantages of femoral neck preservation during THA and (2) the clinical and
      radiological outcome of neck-preserving femoral stems. METHODS: A search of the
      English-language literature on neck-preserving THA and on the individual neck
      preserving implants was performed using PubMed, Ovid SP and Science Direct.
      RESULTS: Studies have indicated that neck preservation offers superior tri-planar
      implant stability and allows more accurate restoration of the hip geometry and
      biomechanics. The trend towards tissue sparing surgery has contributed to the
      development of bone-conserving short-stem implants that offer variable levels of
      neck preservation. Despite an initial learning curve, these implants have
      generated promising early clinical results, with low revision rates and high
      outcome scores. However, radiological evaluation of some neck-preserving implants
      has detected a characteristic pattern of proximal femoral bone loss with distal
      cortical hypertrophy. The long-term implications of this finding are not yet
      known. CONCLUSIONS: Preserving the femoral neck during THA has biomechanical
      advantages. However, long-term outcome data are needed on neck-preserving femoral
      stems to evaluate on-going bone remodelling and assess implant performance and
      survival.

PMID- 24082877
TI  - Osteotomy, arthrodesis, and arthroplasty for complex multiapical deformity of the
      leg.
AB  - BACKGROUND: Assessment of diaphyseal deformity in the tibia consists of
      delineating anatomic axes or cortical lines with resultant apices of deformity.
      Single-apex deformities have been well described both in terms of assessment and
      treatment, whereas double-level deformities with metaphyseal and/or juxtacortical
      involvement are less straightforward. Multiapical deformities of the lower
      extremity, though uncommon, are the next level of complexity and provide the
      surgeon with a difficult correctional mission. CASE DESCRIPTION: We report two
      cases of multiapical deformity of the tibia, both of which were secondary to a
      distant history of tibial fracture with resultant knee and ankle joint
      degeneration and deformity. Both cases had three levels of deformity that were
      addressed with tibial osteotomy, ankle fusion, and total knee replacement.
      Initial presentation, problem lists, surgical treatment, and subsequent results
      are reviewed. LITERATURE REVIEW: Treatment of a post-traumatic three-level
      deformity has never specifically been addressed in the literature, although the
      principles of treatment are the same as for less complex deformities. PURPOSES
      AND CLINICAL RELEVANCE: These two cases present a treatment approach for complex,
      multiapical deformity of the tibia. The same principles of deformity correction
      used to treat less complex deformities are applied to these patients with an
      overarching synthesis that takes all aspects of the three deformities into
      account. Although these cases are complex and difficult, good results in terms of
      deformity correction and pain relief can be obtained.

PMID- 24082878
TI  - Peripheral sympathectomy as a novel treatment option for distal digital necrosis
      following parenteral administration of promethazine.
AB  - Promethazine is a commonly used medication to treat nausea and motion sickness.
      Case reports have recently surfaced on the dangers of parenteral administration
      of promethazine. We present a case report of a presumed intravenous injection of
      promethazine into an antecubital intravenous line resulting in necrosis of the
      ring finger distal to the DIP joint and hypoperfusion of the digits. Peripheral
      sympathectomy was performed to improve nutritional flow and improve ischemic
      pain. However, although this novel treatment option was successful, ultimately
      the patient had an amputation of her ring finger at the level of her middle
      phalanx. Although no proven successful treatment exists, the updated treatment
      options following inadvertent intra-arterial or perivascular administration are
      presented. Given the limited success of current treatment options for intra
      arterial or perivascular extravasation, the staggering medical malpractice awards
      in such cases, and the numerous therapeutic alternatives to promethazine, the
      medical community should question the safety and continued administration of
      promethazine by an intravenous route. 

PMID- 24082879
TI  - Churg-strauss syndrome with eosinophilic myocarditis: a clinical pathology
      conference held by the division of rheumatology at hospital for special surgery.

PMID- 24082880
TI  - Faecal short-chain fatty acid pattern in childhood coeliac disease is normalised
      after more than one year's gluten-free diet.
AB  - OBJECTIVE: Recent work indicates that the gut microflora is altered in patients
      with coeliac disease (CD). Faecal short-chain fatty acids (SCFAs) are produced by
      the gut microflora. We have previously reported a high SCFA output in children
      with symptomatic and asymptomatic CD at presentation, as well as in CD children
      on a gluten-free diet (GFD) for less than 1 year, indicating deviant gut
      microfloral function. In this report, we focus on faecal SCFA production in
      coeliacs on GFD for more than 1 year. MATERIALS AND METHODS: Faecal samples were
      collected from 53 children with CD at presentation, 74 coeliac children on GFD
      for less than 1 year, and 25 individuals diagnosed with CD in childhood and on
      GFD for more than 1 year. The control group comprised 54 healthy children (HC).
      The faecal samples were analysed to show the SCFA pattern taken as a marker of
      gut microflora function. We applied a new fermentation index, reflecting the
      inflammatory activity of the SCFAs (amount of acetic acid minus propionic acid
      and n-butyric acid, together divided by the total amount of SCFAs). RESULTS: In
      coeliacs on GFD for more than 1 year, the individual SCFAs, total SCFA, and
      fermentation index did not differ significantly from the findings in controls. In
      contrast, the faecal SCFA level was clearly higher in coeliacs treated with GFD
      for less than 1 year compared to those more than 1 year. CONCLUSIONS: This is the
      first study on SCFA patterns in faecal samples from individuals with CD on GFD
      for more than 1 year. Our study indicates that the disturbed gut microflora
      function in children with CD at presentation and after less than 1 year of GFD,
      previously demonstrated by us, is normalised on GFD for more than 1 year.

PMID- 24082881
TI  - Psoriasis and Cardiovascular Risk: Assessment by CUORE Project Risk Score in
      Italian Patients.
AB  - Background. Psoriasis is a common inflammatory and immune-mediated skin disease.
      There is growing controversy as to whether cardiovascular risk is elevated in
      psoriasis. A number of studies suggest a high prevalence of cardiovascular risk
      factors as well as cardiovascular diseases in psoriasis patients. Objective. The
      objective of this study was to estimate cardiovascular risk score in psoriasis
      patients and the relation between cardiovascular risk and psoriasis features.
      Cardiovascular risk was assessed by CUORE project risk score built within the
      longitudinal study of the Italian CUORE project and suited to populations with a
      low rate of coronary heart disease. Results. A case-control study in 210
      psoriasis outpatients and 111 controls with skin diseases other than psoriasis
      was performed. CUORE project risk score was higher in patients than controls
      (6.80 +/- 6.34 versus 4.48 +/- 4.38, P < 0.001). Compared to controls, psoriasis
      patients have higher risk of developing major cardiovascular events.
      Cardiovascular risk was not related to psoriasis characteristics. Conclusion.
      Increased focus on identifying cardiovascular risk factors and initiation of
      preventive lifestyle changes or therapeutic interventions in patients with
      psoriasis is warranted. 

PMID- 24082882
TI  - 4D Clinical Imaging for Dynamic CAD.
AB  - A basic 4D imaging system to capture the jaw motion has been developed that
      produces high resolution 3D surface data. Fluorescent microspheres are brushed
      onto the areas of the upper and the lower arches to be imaged, producing a high
      contrast random optical pattern. A hand-held imaging device operated at about 10
      cm from the mouth captures time-based perspective images of the fluorescent
      areas. Each set of images, containing both upper and the lower arch data, is
      converted to a 3d point mesh using photogrammetry, thereby providing an
      instantaneous relative jaw position. Eight 3d positions per second are captured.
      Using one of the 3d frames as a reference, incremental transforms are derived to
      express the free body motion of the mandible. Conventional 3d models of the
      dentition are directly registered to the reference frame, allowing them to be
      animated using the derived transforms. 

PMID- 24082884
TI  - Sinonasal cancer and occupational exposure in a population-based registry.
AB  - We examined occupational exposures among subjects with sinonasal cancer (SNC)
      recorded in a population-based registry in the Lombardy Region, the most
      populated and industrialized Italian region. The registry collects complete
      clinical information and exposure to carcinogens regarding all SNC cases
      occurring in the population of the region. In the period 2008-2011, we recorded
      210 SNC cases (137 men, 73 women). The most frequent occupational exposures were
      to wood (44 cases, 21.0%) and leather dust (29 cases, 13.8%), especially among
      men: 39 cases (28.5%) to wood and 23 cases (16.8%) to leather dust. Exposure to
      other agents was infrequent (<2%). Among 62 subjects with adenocarcinoma, 50% had
      been exposed to wood dust and 30.7% to leather dust. The proportions were around
      10% in subjects with squamous cell carcinoma and about 20% for tumors with
      another histology. The age-standardized rates (*100,000 person-years) were 0.7 in
      men and 0.3 in women. Complete collection of cases and their occupational history
      through a specialized cancer registry is fundamental to accurately monitor SNC
      occurrence in a population and to uncover exposure to carcinogens in different
      industrial sectors, even those not considered as posing a high risk of SNC, and
      also in extraoccupational settings. 

PMID- 24082883
TI  - Ewing sarcoma protein: a key player in human cancer.
AB  - The Ewing sarcoma protein (EWS) is a well-known player in cancer biology for the
      specific translocations occurring in sarcomas. The EWS-FLI1 gene fusion is the
      prototypical translocation that encodes the aberrant, chimeric transcription
      factor, which is a landmark of Ewing tumors. In all described Ewing sarcoma
      oncogenes, the EWS RNA binding domains are completely missing; thus RNA binding
      properties are not retained in the hybrid proteins. However, it is currently
      unknown whether the absence of EWS function in RNA metabolism plays a role in
      oncogenic transformation or if EWS plays a role by itself in cancer development
      besides its contribution to the translocation. In this regard, recent reports
      have highlighted an essential role for EWS in the regulation of DNA damage
      response (DDR), a process that counteracts genome stability and is often
      deregulated in cancer cells. The first part of this review will describe the
      structural features of EWS and its multiple roles in the regulation of gene
      expression, which are exerted by coordinating different steps in the synthesis
      and processing of pre-mRNAs. The second part will examine the role of EWS in the
      regulation of DDR- and cancer-related genes, with potential implications in
      cancer therapies. Finally, recent advances on the involvement of EWS in
      neuromuscular disorders will be discussed. Collectively, the information reviewed
      herein highlights the broad role of EWS in bridging different cellular processes
      and underlines the contribution of EWS to genome stability and proper cell-cycle
      progression in higher eukaryotic cells. 

PMID- 24082885
TI  - Gastric tuberculosis with outlet obstruction: a case report presenting with a
      mass lesion.
AB  - Tuberculosis is a major health problem worldwide. In India, it is highly endemic.
      The most common manifestation is a pulmonary disease, but involvement of the
      gastrointestinal tract is not uncommon with the ileocecal region being the
      commonest site. Gastric tuberculosis is rare and usually associated with
      pulmonary tuberculosis or an immunodeficient state. Here, we report a case of
      gastric tuberculosis presenting as gastric outlet obstruction in an
      immunocompetent patient without evidence of pulmonary tuberculosis. Biopsy and
      PCR confirmed the diagnosis, and the patient responded well to standard
      antitubercular treatment. Though, gastric tuberculosis is rare, it should be
      considered as a possibility when patients present with gastric outlet
      obstruction, particularly in endemic areas with tuberculosis. 

PMID- 24082886
TI  - Iatrogenic obliteration of ureter with spontaneous recanalization.
AB  - We report an unusual case of spontaneous and complete healing of a severe
      iatrogenic midureteral injury. Following percutaneous nephrostomy and 3 months on
      our surgical waiting list, the injured ureter underwent complete spontaneous
      recanalization. The patient is clinically well with no evidence of recurrent
      obstruction after 2 years of followup. To our knowledge, this is the first
      reported case of spontaneous recanalization of an iatrogenically induced complete
      ureteral obliteration. 

PMID- 24082887
TI  - Autoimmune Hepatitis Triggered by Anti-TNF-alpha Therapy.
AB  - Autoimmune hepatitis (AIH) is occasionally triggered by drug treatments.
      Recently, as biological agents are becoming widely used for autoimmune disorders,
      there have been a growing number of reports of the development of autoimmune
      processes related to these agents. A 52-year-old Japanese woman with psoriasis
      developed liver damage two months after initiation of anti-TNF- alpha therapy
      with adalimumab. Liver histological findings were compatible with AIH, and
      positive conversions of ANAs were detected. The patient was treated with
      prednisolone and had a good response. While some cases of AIH triggered by anti
      TNF- alpha therapies have been reported, the pathogenesis remains unspecified.
      When elevation of liver enzymes is observed with high IgG levels and
      seropositivity of ANA during the course of anti-TNF- alpha therapy, liver biopsy
      findings may be essential and important to make definitive diagnosis of AIH. 

PMID- 24082888
TI  - Effects of severe hypoxia on bone marrow mesenchymal stem cells differentiation
      potential.
AB  - Background. The interests in mesenchymal stem cells (MSCs) and their application
      in cell therapy have resulted in a better understanding of the basic biology of
      these cells. Recently hypoxia has been indicated as crucial for complete
      chondrogenesis. We aimed at analyzing bone marrow MSCs (BM-MSCs) differentiation
      capacity under normoxic and severe hypoxic culture conditions. Methods. MSCs were
      characterized by flow cytometry and differentiated towards adipocytes,
      osteoblasts, and chondrocytes under normoxic or severe hypoxic conditions. The
      differentiations were confirmed comparing each treated point with a control point
      made of cells grown in DMEM and fetal bovine serum (FBS). Results. BM-MSCs from
      the donors displayed only few phenotypical differences in surface antigens
      expressions. Analyzing marker genes expression levels of the treated cells
      compared to their control point for each lineage showed a good differentiation in
      normoxic conditions and the absence of this differentiation capacity in severe
      hypoxic cultures. Conclusions. In our experimental conditions, severe hypoxia
      affects the in vitro differentiation potential of BM-MSCs. Adipogenic,
      osteogenic, and chondrogenic differentiations are absent in severe hypoxic
      conditions. Our work underlines that severe hypoxia slows cell differentiation by
      means of molecular mechanisms since a decrease in the expression of adipocyte-,
      osteoblast-, and chondrocyte-specific genes was observed. 

PMID- 24082889
TI  - Occult hepatitis C virus infection in candidates for liver transplant with
      cryptogenic cirrhosis.
AB  - BACKGROUND: Occult hepatitis C virus (HCV) infection is a new entity described by
      the presence of HCV-RNA in liver biopsy and/or peripheral blood mononuclear cell
      (PBMC) specimens, and undetectable levels or absence of HCV-RNA and in the
      absence or presence of anti HCV antibodies in plasma by current laboratory
      methods. OBJECTIVES: To evaluate the detection of HCV-RNA in PBMC specimens of
      the liver transplant candidates with cryptogenic cirrhosis by reverse
      transcriptase-nested polymerase chain reaction (RT-nested PCR). PATIENTS AND
      METHODS: From November 2007 to March 2013, 45 patients from Liver Transplant
      Center of Imam Khomeini Hospital, Tehran, were enrolled in this cross sectional
      study. PBMC specimens were separated from the peripheral blood sample. After
      extraction of RNA from plasma and PBMC specimens, HCV-RNA status was tested by RT
      nested PCR. The 5'-untranslated region (5'-UTR) genotyping of HCV-RNA amplified
      from PBMC specimens was performed by a standard methodology with the INNO
      LiPA(TM) HCV II kit. The PCR products of 5'-UTR were sequenced after cloning into
      the pJET1.2 / blunt cloning vector. RESULTS: Of 45 patients, 4 (8.9% [95% CI: 4.4
      15.6]) had detectable genomic HCV-RNA in their PBMC specimens. HCV genotypes were
      determined in the PBMCs of these subjects showed that 2 (50.0%) subjects with
      occult HCV infection had HCV subtype 3a, and 2 (50.0%) had HCV subtype 1b.
      CONCLUSIONS: This study found that 8.9 % of the Iranian candidates for liver
      transplant with cryptogenic cirrhosis had occult HCV infection. Therefore,
      designing prospective studies focusing on the diagnosis of occult HCV infection
      in these subjects prior to liver transplantation could be valuable.

PMID- 24082890
TI  - In Vitro Analysis of CsA-Induced Hepatotoxicity in HepG2 Cell Line: Oxidative
      Stress and alpha2 and beta1 Integrin Subunits Expression.
AB  - BACKGROUND: Cyclosporine A (CsA)-induced hepatotoxicity could be due to a
      reduction in alpha2beta1 integrin expression that may either be from the direct
      effect of CsA itself or from reactive oxygen species (ROS) overproduction.
      OBJECTIVES: In this study we aimed to identify the cellular mechanisms underlying
      CsA-induced hepatic injury by investigating the activation patterns of the
      antioxidant enzymes, using HepG2 as an in vitro model. MATERIALS AND METHODS:
      HepG2 cells were cultured with different concentrations of CsA (0, 0.1, 1, 10
      MUg/ml) for 72 h. Effect of CsA on, 1) cellular integrity, 2) glutathione
      reductase (GR) and glutathione peroxidase (GPx) activity, 3) cellular levels of
      glutathione (GSH), 4) intracellular ROS, 5) ALT and AST activities, 6) urea
      production and 7) alpha2beta1 integrin expression were assayed. RESULTS: CsA
      treatment demonstrated a dose dependent increase in intracellular levels of ROS,
      GPx activity and decrease in GSH levels (P<0.05). GR activity was mildly
      attenuated in 1 and 10 ug/ml concentrations of CsA. Alanine aminotranferase (ALT)
      and aspartate aminotransferase (AST) levels increased in CsA treated cells, while
      urea synthesis was significantly decreased following treatment with higher
      concentrations of CsA (P<0.05). Significant down-regulation of beta1integrin
      expression was observed in 1 and 10 ug/ml CsA treated cells while alpha2 integrin
      mRNA was significantly down-regulated in all CsA treated cells. CONCLUSIONS: The
      observed reduction of alpha2beta1 integrin expression following CsA treatment
      could be proposed as a possible pathway of CsA-induced hepatotoxicity. Further
      studies are required to elucidate whether this attenuated expression is due to
      the direct effect of CsA or caused by overproduction of ROS.

PMID- 24082891
TI  - Preparation and characterization of a sustained release buccoadhesive system for
      delivery of terbutaline sulfate.
AB  - Terbutaline sulfate exhibits extensive first pass metabolism and a short
      elimination half life which makes frequent oral administration of the drug
      inevitable. A novel buccoadhesive controlled delivery system of the drug can
      easily overcome the problem. A two-layered core tablet composed of a fast release
      layer made of mannitol, lactose, PEG and the drug attached to a sustained release
      layer composed of drug, varying ratios of HPMC, Carbomer 934 (CP), and lactose
      capped with a buccoadhesive cup coated with an impermeable backing layer was
      developed. Buccoadhesive cup initially optimized for bioadhesion strength using
      HPMC and CP with various ratios. Drug transport through buccal membrane indicated
      a high permeability coefficient (0.00105 cm/sec). All tablets were acceptable
      with regard to drug contents, thickness, weight variations, hardness and drug
      content uniformity. The CP:HPMC 2:1 mixture showed the best mucoadhesion
      properties and was selected as excipient for the cup layer. Swelling index was
      higher for formulations containing greater amount of lactose and lower percentage
      of polymers. Fast release layer released its entire content within 15 min while
      sustained release layer lasted for 12 h. Drug release controlled by a combination
      of diffusion and chain relaxation mechanism. 

PMID- 24082892
TI  - Synthesis and tyrosinase inhibitory properties of some novel derivatives of kojic
      acid.
AB  - Tyrosinase is a multifunctional oxidase that is widely distributed in nature. It
      is a key enzyme in melanin biosynthesis and is involved in determining the color
      of mammalian skin and hair. In addition it is responsible for the undesirable
      enzymatic browning that occurs in plant-derived foods, limiting the shelf-life of
      fresh-cut products with the resultant economic loss. In recent years there has
      been considerable interest to study the inhibitory activity of tyrosinase and a
      number of inhibitory compounds derived from natural sources or partly/fully
      synthetic have been described. However, the current conventional methods to
      control tyrosinase action are inadequate. Considering the significant industrial
      and economic impact of the inhibitors of tyrosinase, this study was set to seek
      new potent inhibitors of this enzyme. A series of 3-hydroxypyridine-4-one
      derivatives were prepared in high yield and evaluated for their inhibitory
      activity on tyrosinase enzyme using dopachrome method. Our results show that all
      synthesized compounds have inhibitory effect on tyrosinase activity for the
      oxidation of L-DOPA. Among compounds studied those containing two free hydroxyl
      group (ie Va and V'a) were more potent than their analogues with one hydroxyl
      group (ie Vb and V'b). Also substitution of a methyl group on position N(1) of
      the hydroxypyridinone ring seems to confer more inhibitory potency. 

PMID- 24082893
TI  - Regulatory effect of caffeic acid phenethyl ester on type I collagen and
      interferon-gamma in bleomycin-induced pulmonary fibrosis in rat.
AB  - Idiopathic pulmonary fibrosis (IPF) is a chronic lung disease of unknown
      etiology. Recent investigations have demonstrated that the impaired immune
      response is a common characteristic feature of IPF. Unfortunately, no definitive
      and effective drug treatment is available that could improve or at least inhibit
      the progressive course of this fatal disease. That is why one of the main
      priorities of pulmonary fibrosis investigations is to identify novel and
      effective molecular targets for preventive and therapeutic interventions. caffeic
      acid phenethyl ester (CAPE) is one of the most interesting bioactive compounds
      extracted from bee propolis. It has been shown that CAPE has an antioxidant
      activity and modulatory impact on immune system. Accordingly, the aim of the
      present study was to investigate the regulatory effects of CAPE on the levels of
      type I collagen (COL-1) and Interferon-gamma (IFN-gamma) in bleomycin (BLM)
      induced pulmonary fibrosis. Immunohistochemistry procedure was employed to assess
      the effects of CAPE on lung tissue. In this study, male Sprague-Dawley rats were
      divided into 5 groups (n=8) included 1: Positive control group: bleomycin (BLM).
      2: Negative (saline) control group. 3, 4: Treatment groups of 1 and 2: BLM+CAPE
      (5 and 10 MUmol/kg/day, respectively). (5: Sham group: CAPE (10 MUmol/kg/day).
      BLM application resulted in significant changes in the level of studied
      parameters as compared to the controls. CAPE could decrease type I collagen
      concentration, modulate IFN-gamma level, increase the animals' body weight and
      decrease the lung index dose-dependently, compared with model group. In
      conclusion, CAPE may provide a novel therapeutic target for treating pulmonary
      fibrosis. 

PMID- 24082894
TI  - Investigation of some biologic activities of Swertia longifolia Boiss.
AB  - Swertia species are widespread in Eastern and Southern Asian countries and used
      in traditional medicine as anti-pyretic, analgesic, gastro and liver tonic. Among
      different species, only Swertia longifolia grows in Iran. In this investigation,
      antioxidant, cytotoxic and acetylcholinesterase inhibitory activities of S.
      longifolia have been studied. Aerial parts and roots of the plant were collected,
      dried and extracted with methanol 80% (total extract). Different extracts of the
      plant were obtained using hexane, chloroform, ethyl acetate, methanol,
      methanol:water (1:1) and water, respectively. Cytotoxic activity was determined
      by MTT assay on MDBK, HepG2, MCF7, HT29 and A549 cell lines. Antioxidant activity
      was measured by 2,2-diphenyl-1-picryl hydrazyl (DPPH) free radicals and
      acetylcholinesterase inhibitory (AChEI) effect was evaluated based on Ellman's
      method in 96-well microplates.The results showed no cytotoxicity of the plant
      extracts on MDBK, HepG2, MCF7, HT29 and A549 cell lines up to 100 MUg/ml. All
      samples showed radical scavenging activity but methanol extract of aerial parts
      and ethyl acetate extract of the roots showed the highest effects.Total extract
      of the roots showed higher AChEI activity than the aerial parts. Among different
      extracts, chloroform and ethyl acetate extracts of the roots and chloroform and
      methanol:water extracts of the aerial parts were more potent in AChEI assay. It
      is concluded that aerial parts and roots of the plant are rich in antioxidant
      agents with no cytotoxicity on selected cell lines up to 100 MUg/ml. Moreover,
      since antioxidant and AChEI activity of compounds play an important role in the
      treatment of Alzheimer's disorder, this plant might be a potential candidate for
      isolation of antioxidant and AChEI compounds which could be used as supportive
      treatment of Alzheimer's disease. 

PMID- 24082895
TI  - In vitro anti-bacterial and anti-adherence effects of Lactobacillus delbrueckii
      subsp bulgaricus on Escherichia coli.
AB  - Considering the emergence of antibiotic resistance, scientists are interested in
      using new antimicrobial agents in the treatment of infectious diseases including
      infections of the enteric systems. Lactic acid bacteria have the great potential
      to produce antimicrobial compounds that inhibit and control pathogenic bacteria.
      The aim of this study was to determine the anti-bacterial and anti-adherence
      properties of Lactobacillus delbrueckii subsp bulgaricus against Escherichia
      coli. The antibacterial activity of L. delbrueckii was investigated using disc
      diffusion and spot on lawn methods. In vitro anti-adhesion effect of L.
      delbrueckii against E. coli was examined using Caco-2 cells. In anti-adhesion
      assay, three competition conditions including competitive inhibition, adhesion
      inhibition, and displacement were examined. In spot on lawn method the zone of
      growth inhibition of E. coli by L. delbrueckii was 21.1 mm. The cell free
      supernatant of L. delbrueckii showed a good antibacterial activity against E.
      coli which was mainly related to lactic acid produced by L. delbrueckii. When two
      bacteria added simultaneously (competitive inhibition) degree of inhibition of E.
      coli binding by L. delbrueckii was 77%. In adhesion inhibition assay, L.
      delbrueckii was able to exclude E. coli adherence by around 43.5%. Displacement
      assay showed that L. delbrueckii had strong displacement ability toward E. coli
      and reduction of E. coli attachment by bound L. delbrueckii was 81.3%. The
      results suggest that L. delbrueckii may be able to inhibit E. coli infection in
      the gut; however more studies including in vivo studies need to be performed. 

PMID- 24082897
TI  - Effect of Rosa damascena Mill. flower extract on rat ileum.
AB  - Rosa damascena flower is widely used for gastrointestinal (GI) disorders.
      However, its pharmacological action on isolated ileum has not been studied. In
      this research, the effect of extract of flower petals of R. damascena Mill.
      growing in Kashan, Iran, on ileum motility was investigated. Hydroalcoholic
      extract was prepared by percolation method. A section of rat ileum was suspended
      in an organ bath containing Tyrode's solution. The tissue was stimulated with
      electrical field stimulation (EFS), KCl and acetylcholine (ACh). The tissue was
      kept under 1g tension at 37 degrees C and continuously gassed with O2. Effect of
      the R. damascena extract was studied on ileum contractions induced by EFS, KCl
      and ACh and compared with that of atropine. R. damascena extract (10-100 mg/ml)
      induced a contraction in rat isolated ileum while at 1mg bath concentration it
      had relaxant effect on rat ileum. Hydroalcoholic extract of R. damascena (1-8
      mg/ml) concentration dependently inhibited ileum contraction induced by KCl
      (IC50=3.3 +/- 0.9 mg/ml), ACh (IC50=1.4 +/- 0.1 mg/ml) and EFS (IC50=1.5 +/- 0.3
      mg/ml). The vehicle had no significant effect on ileum contractions. From this
      experiment it was concluded that R. damascena extract at microgram concentrations
      had stimulatory effect on ileum smooth muscle. However, at milligram
      concentrations, it shows an inhibitory effect. This is most likely due to
      presence of different components in the extract. The stimulatory effect of the
      extract confirms its benefits for the treatment of constipation. Therefore,
      separation and identification of active components is recommended. 

PMID- 24082896
TI  - Chemical composition and anxiolytic evaluation of Achillea Wilhelmsii C. Koch
      essential oil in rat.
AB  - Herbal based remedies are used worldwide to treat psychiatric disorders. The aim
      of this study was to analyse the essential oil composition of Achillea Wilhemsii
      C. Koch (Asteraceae) and to evaluate its anxiolytic effects in the elevated plus
      maze (EPM) model of anxiety in rat. Gas chromatography/mass spectrometry (GC/MS)
      analysis of the essential oil showed that the main compounds of the oil were p
      ocimen (23%), 1, 8-cineole (20.8%) and carvone (19.13%). The EPM results showed
      that 1 mg/kg (i.p.) of the oil significantly (P<0.05) increased the percentage of
      the time spent and the number of entries in the open arms of the maze while it
      did not change the total number of entries in the maze arms. These effects were
      not reversed with 2 mg/kg flumazenil and 5 mg/kg naloxone. We concluded that a
      minimum dose of 1 mg/kg of the oil has anxiolytic effects which are not probably
      mediated through GABA and opioid receptors. 

PMID- 24082898
TI  - Density functional theory study of the local molecular properties of acetamide
      derivatives as anti-HIV drugs.
AB  - Accurate quantum chemical computations based on density functional theory (DFT)
      were performed on the series of 2-(4-(naphthalen-2-yl)-1,2,3-thiadiazol-5-ylthio)
      N-acetamide (TTA) derivatives. The local reactivity of the acetamide derivatives
      as anti-HIV drugs were studied in terms of Fukui functions in the framework of
      DFT. The results based on the basis set superposition error (BSSE) corrections
      showed that the mechanism of bond formation between the acetamide derivatives and
      tyrosine as a biological molecule occurs mainly through nitrogen atoms. The
      intramolecular interaction energies between the acetamide derivatives and
      tyrosine were calculated and the nature of the intermolecular interaction was
      revealed by natural bond orbital charge (NBO) analysis. The results suggest that
      acetamide derivatives with bromophenyl and nitrophenyl substitutions are the most
      potent as anti-HIV drugs. 

PMID- 24082899
TI  - In vitro cytotoxic evaluation of some synthesized COX-2 inhibitor derivatives
      against a panel of human cancer cell lines.
AB  - Celecoxib is a non-steroidal anti-inflammatory drug (NSAID) developed as a
      selective inhibitor of cyclooxygenase-2 (COX-2) for the treatment of rheumatoid
      arthritis disease. Recently some other mechanisms have been identified for anti
      cancer activity of these agents including induction of apoptosis, inhibition of
      tumor vascularization, stimulation of antitumor immune responses and inhibition
      of cellular protein synthesis. The cytotoxic effects of four synthesisized
      analogues of celecoxib (coded as D, E, F and G) were evaluated against Hela, MDA
      MB-231, A-2780-s and HT-29 cancer cells, using MTT assay; Also their induction of
      apoptosis using DNA fragmentation analysis were studied. MTT assay showed that
      cell survival percent of COX-2 positive cell lines (HT-29, MDA-MB-231 and Hela;
      p<=0.05) were decreased significantly after exposure to the tested COX-2
      inhibitors while little effect was observed on the COX-2 negative cell line (A
      2780-s). Results also showed that A-2780-s and Hela were the most resistant and
      the most sensitive cell lines to these compounds, respectively. Moreover, in DNA
      fragmentation assay, induction of apoptosis was confirmed by electrophoretic
      pattern of separated DNA fragments in Hela cell line. Compounds E and G in
      comparison with D and F exerted more cytotoxic effect on COX-2 positive cell
      lines (Hela, HT-29 and MDA-MB-231). This could be due to the hydrophobic
      substituent (Cl, CH3) located at the para position of phenyl ring leading to more
      lipophilicity and cell uptake. In addition, these COX-2 inhibitors induced
      apoptosis on Hela cell-line, which could be considered as one of the cytotoxic
      mechanisms of these compounds as potential anti cancer agents. 

PMID- 24082900
TI  - Effect of different luting cements on fracture resistance in endodontically
      treated teeth.
AB  - INTRODUCTION: The aim of the present study was to evaluate the effect of three
      types of luting cements used for post cementation on the fracture resistance of
      endodontically treated maxillary premolars, restored with resin composite.
      MATERIALS AND METHODS: One hundred intact single-rooted human maxillary premolars
      were randomly divided into 5 groups of 20 each. In groups 2-5, post spaces were
      prepared after root canal treatment and clinical crown reduction up to 1.5 mm
      above the CEJ. Teeth were divided in groups as follows: Group 1: intact teeth,
      Group 2: active prefabricated metallic posts (PMP), Group 3: PMP cemented with
      zinc phosphate luting cement, Group 4: PMP cemented with glass ionomer luting
      cement and Group 5: PMP cemented with resin luting cement. In groups 2-5 the
      teeth were restored with resin composite. Following thermocycling, the palatal
      cusp of each specimen was loaded to compression at an angle of 150 to its
      longitudinal axis at a strain rate of 2 mm/min until fracture occurred. Data were
      analyzed using one-way ANOVA and a post hoc Tukey test. Chi-square test was used
      for comparison of failure mode. RESULTS: There were significant differences in
      fracture resistance between the test groups (P<0.001). The differences between
      group 2 with groups 1, 4 and 5 were statistically significant (P<0.05); whereas
      there were no significant differences in fracture resistance between the two
      other groups (P>0.05). Furthermore, there were no significant differences in the
      mode of failure between the 5 groups (P>0.05). CONCLUSION: Zinc phosphate, glass
      ionomer and resin luting cements showed similar behaviors and achieved fracture
      resistance comparable to intact teeth. However, the use of active post (without
      cement) adversely affected the fracture resistance of root canal treated teeth.

PMID- 24082901
TI  - Antimicrobial Effects of AH26 Sealer/Antibiotic Combinations Against Enterococcus
      Faecalis.
AB  - INTRODUCTION: The purpose of this in vitro study was to evaluate the
      antimicrobial effects of two antibiotics added to AH26 sealer against
      Enterococcus faecalis (EF). MATERIALS AND METHODS: The antimicrobial effects of
      two antibiotic (amoxicillin and doxycycline) that were added separately to AH26
      sealer was evaluated by using the agar diffusion test and in vitro human root
      inoculation method. The freshly mixed sealers were placed in prepared wells
      inside agar plates inoculated with EF, and were incubated at 37( degrees )C. The
      zones of inhibition were measured at 24, 48, 72 hours and 7 days. Root specimens
      were prepared and obturated with lateral condensation technique. Samples were
      collected from infected root canals after 2 and 7 days of incubation and the
      number of colony-forming units (CFU) was determined. The data were analyzed using
      one-way and two-way ANOVA. RESULTS: The findings of this study revealed that
      sealer-antibiotic combination containing amoxicillin and doxycycline had a
      significant difference in the mean zones of inhibition when compared to AH26
      sealer alone in all of the time periods (P<0.05). The minimum effective
      concentration against EF was one percent of sealer powder weight for both of
      amoxicillin and doxycyline. The mean log10 CFU in AH26-doxycyline combination
      group was significantly lower than other groups at 48 h incubation period
      (P<0.05). AH26-doxycycline combination group and AH26-Amoxicillin combination
      group killed bacteria (mean CFU=0) in the dentinal tubules at 7 days incubation
      period. CONCLUSION: In vitro root fillings carried out with gutta-percha and AH26
      antibiotic combination were effective in killing EF in dentinal tubules.

PMID- 24082902
TI  - Comparison of extracted teeth and simulated resin blocks on apical canal
      transportation.
AB  - INTRODUCTION: We aimed to compare apical canal transportation of extracted teeth
      and two types of simulated resin blocks. MATERIALS AND METHODS: Mesiobuccal root
      of extracted maxillary molars, high hardness simulated resin blocks (Knoop
      hardness=40) and low hardness simulated resin blocks (Knoop hardness=22) were
      prepared with K-files using step-back technique (n=15 canals in each group).
      Double exposure radiographic technique was used for extracted teeth. Simulated
      resin blocks were stabilized and scanned before and after preparation. Pre and
      post-preparation pictures were superimposed and apical transportation was
      measured. The data were analyzed statistically using ANOVA and Tukey HSD tests.
      RESULTS: There was no significant difference in apical canal transportation
      between extracted teeth and high hardness resin blocks (P>0.05). Low hardness
      resin blocks showed more apical transportation than the other groups (P<0.05).
      CONCLUSION: Under the conditions of this study, apical canal transportation for
      extracted teeth and high hardness simulated resin blocks were similar.

PMID- 24082903
TI  - Stress distribution changes after root canal therapy in canine model: a finite
      element study.
AB  - INTRODUCTION: The fracture strength of endodontically treated teeth compared to
      vital ones has long been a source of controversy. It is not clear how root canal
      therapy affects the stress distribution in teeth. The purpose of this study was
      to evaluate the changes in stress distribution after root canal therapy in a
      human maxillary canine by finite element analysis (FEM). MATERIALS AND METHODS:
      Two 3D FEM models of a maxillary canine were created; one represented a virgin
      tooth and the other represented the same tooth after root canal therapy. A single
      force of 14.1 N was applied 45 degrees to horizontal plane to the center of the
      palatal surface; stress distribution was then analyzed in both models. RESULTS:
      SEQV (VonMises stress) analysis demonstrated an obvious decrease after root canal
      therapy and the regions near cementoenamel junction (CEJ) showed the highest
      displacement. The endodontically treated tooth demonstrated higher deflection
      than the vital one. CONCLUSION: Maximum stress and displacement was repeatedly
      found in the cervical area, hence more emphasis should be placed on the
      reinforcement of this region.

PMID- 24082904
TI  - A comparative scanning electron microscope investigation of cleanliness of root
      canals using hand k-flexofiles, rotary race and k3 instruments.
AB  - INTRODUCTION: The most important aims of root canal preparation are the removal
      of vital pulp tissue, remaining necrotic debris and infected dentin, eliminating
      the bulk of bacteria present in the root canal system. The aim of this study was
      to compare the cleaning efficacy of hand K-Flexofiles and rotary RaCe and K3
      instruments in root canal preparation. MATERIALS AND METHODS: A total of 60
      single rooted teeth with maximum curvature of <20o were selected and divided into
      three groups of 20 teeth each. Canals were prepared with K-Flexofiles, K3 and
      RaCe instruments using crown down preparation technique, up to size #30. After
      instrumentation, the root canals were flushed with 5 mL of 2.5 % NaOCl solution.
      The amount of debris and smear layer was quantified on the basis of Hulsmann
      method using a scanning electron microscope. The data were statistically analyzed
      with one-way ANOVA test at a significance level of P<0.05. RESULTS: None of the
      three groups achieved completely debrided root canals.. In general, K-Flexofiles
      were able to achieve cleaner canals compared to K3 and RaCe instruments (P<0.05).
      There were no significant differences between three groups in smear layer removal
      throughout the root canal walls (P<0.05). CONCLUSION: K-Flexofiles group had less
      remained debris when compared to K3 and RaCe instruments.

PMID- 24082905
TI  - A Comparative Study of Antimicrobial Activity of Proroot MTA, Root MTA, and
      Portland Cement on Actinobacillus Actinomycetemcomitans.
AB  - INTRODUCTION: The purpose of our study was to evaluate the antibacterial effect
      of ProRoot MTA (PRMTA), Root MTA (RMTA) and Portland cement (PC) at their
      clinical concentration (70 mg/25 uL) against Actinobacillus actinomycetemcomitans
      (Aa) one of the prominent periodontal (pocket) microorganisms. MATERIALS AND
      METHODS: Agar diffusion test on Blood Agar with Hemin and Vitamin K (BAHV) was
      employed in this study. The microorganisms were seeded on the BAHV by spreaders.
      Small holes, 6 mm in diameter, were made in the BAHV by removing agar. PRMTA,
      RMTA and PC were placed into the wells immediately after manipulation. The plates
      were incubated in anaerobic atmosphere at 37 degrees C for 72 h and the zones of
      inhibition were measured. RESULTS: In the agar diffusion test PRMTA, RMTA and PC
      against Aa showed zones of inhibition. Analyzing the antimicrobial activity of
      PRMTA, RMTA and PC according to paired one-way ANOVA and Post Hoc Test (Turkey's
      test) analysis showed a statistically significant difference (P<0.05) between
      PRMTA, RMTA and PC. RMTA showed the largest zone of inhibition (29 mm) against A
      a. There was no difference in the zones of inhibition between the 48 and 72 h
      time periods. CONCLUSION: In this in vitro study PRMTA and RMTA presented similar
      antimicrobial activity against Aa.

PMID- 24082906
TI  - Endodontic treatment of a large periradicular lesion: a case report.
AB  - This case report describes the endodontic treatment of a large cyst-like
      periradicular lesion a 29-year-old female with a large chronic periapical abscess
      in the region of right maxillary sinus presented into private practice,
      accompanied with non-vital first upper molar and poorly root treated second upper
      molar. Conservative root canal treatment was carried out for both of the involved
      teeth in a single appointment. Post operative examination after two weeks
      revealed complete resolution of the sinus tract. The clinical and radiographic
      examination after 9 months revealed complete periapical healing. The appropriate
      diagnosis of periradicular lesion and the treatment of the infected root canal
      system allowed complete healing of these large lesions without endodontic
      surgery. 

PMID- 24082907
TI  - Endodontic treatment of a mandibular second molar with two mesial roots: report
      of a case.
AB  - A case of unusual root morphology is presented to demonstrate anatomic variations
      in mandibular second molars. The most common configuration of mandibular second
      molar is to have two roots with three root canals; however mandibular molars may
      have many different combinations. Endodontic therapy was performed in a
      mandibular second molar with 3 separate roots 2 located mesially and one
      distally. Radiographically all 3 root canals terminated with individual foramina.
      Three orifices or 3 independent canals were found in the 3 separate roots,
      indicating a rare anatomic configuration. Looking for additional roots, canals
      and unusual morphology is an important part of successful endodontics as the
      knowledge of their existence occasionally enable clinicians to treat a case that
      otherwise might have ended in failure. 

PMID- 24082908
TI  - A possible role of HMGB1 in DNA demethylation in CD4+ T cells from patients with
      systemic lupus erythematosus.
AB  - The aberrant activity of CD4(+) T cells in patients with systemic lupus
      erythematosus (SLE) is associated with DNA hypomethylation of the regulatory
      regions in CD11a and CD70 genes. Our previous studies demonstrated that Gadd45a
      contributes to the development of SLE by promoting DNA demethylation in CD4(+) T
      cells. In this study, we identified proteins that bind to Gadd45a in CD4(+) T
      cells during SLE flare by using the method of co-immunoprecipitation and mass
      spectrometry, High mobility group box protein 1 (HMGB1) is one of identified
      proteins. Furthermore, gene and protein expression of HMGB1 was significantly
      increased in SLE CD4(+) T cells compared to controls, and HMGB1 mRNA was
      correlated with CD11a and CD70 mRNA. A significant, positive correlation was
      found between HMGB1 mRNA and SLEDAI for SLE patients. Our data demonstrate that
      HMGB1 binds to Gadd45a and may be involved in DNA demethylation in CD4(+) T cells
      during lupus flare. 

PMID- 24082909
TI  - Serum interleukin-6 expression level and its clinical significance in patients
      with dermatomyositis.
AB  - OBJECTIVE: To analyze serum interleukin-6 (IL-6) expression level and its
      clinical significance in patients with dermatomyositis. METHODS: Blood samples
      from 23 adult patients with dermatomyositis (DM), 22 with systemic lupus
      erythematosus (SLE), 22 with rheumatoid arthritis (RA), 16 with Sjogren's
      syndrome (SS), and 20 healthy controls were collected. The IL-6 concentration was
      detected by chemiluminescence immunoassay. Correlations between IL-6 expression
      levels and clinical features or laboratory findings in patients with DM were
      investigated. RESULTS: IL-6 expression level of DM patients was significantly
      higher than that of normal controls, significantly lower than that of RA
      patients, and slightly lower than that of SLE or SS patients with no significant
      differences. The incidence of fever was significantly higher in the IL-6 elevated
      group. Serum ferritin (SF) and C-reactive protein (CRP) were positively
      correlated with IL-6. CONCLUSIONS: IL-6 plays a less important role in DM than in
      RA. IL-6 monoclonal antibodies may have poor effect in patients with DM.

PMID- 24082910
TI  - Replication of british rheumatoid arthritis susceptibility Loci in two unrelated
      chinese population groups.
AB  - Previous genome-wide association study by WTCCC identified many susceptibility
      loci of common autoimmune diseases in British, including rheumatoid arthritis
      (RA). Because of the genetic heterogeneity of RA, it is necessary to replicate
      these susceptibility loci in other populations. Here, three SNPs with strong RA
      association signal in the British were analyzed in Han Chinese, and two SNPs
      (rs6457617 and rs11761231) were genotyped in the test cohort firstly. The
      rs6457617 was significantly associated with RA in the test cohort. The
      individuals bearing the homozygous genotype CC had 0.39-fold risk than these
      bearing the wild-type genotype TT (P = 0.004, OR 0.39, [95% CI 0.21-0.74]). And
      the protective effect of allele C was confirmed in another validation cohort with
      1514 samples (P genotye CC/TT = 5.9 *  10(-10), OR 0.34, [95% CI 0.24-0.48]). The
      rs6457617 can be used as a tagSNP of HLA-DQA1*03 which encoded MHC-II alpha
      chain. Since MHC restriction is important for primary T-cells in positive
      selection and negative selection stages, MHC protein polymorphisms may be
      implicated in shaping the T-cell repertoire, including the emergence of a T-cell
      clone involved in the inflammatory arthritis. 

PMID- 24082911
TI  - Efficacy of EMG- and EEG-Biofeedback in Fibromyalgia Syndrome: A Meta-Analysis
      and a Systematic Review of Randomized Controlled Trials.
AB  - Objectives. Biofeedback (BFB) is an established intervention in the
      rehabilitation of headache and other pain disorders. Little is known about this
      treatment option for fibromyalgia syndrome (FMS). The aim of the present review
      is to integrate and critically evaluate the evidence regarding the efficacy of
      biofeedback for FMS. Methods. We conducted a literature search using Pubmed,
      clinicaltrials.gov (National Institute of Health), Cochrane Central Register of
      Controlled Trials, PsycINFO, SCOPUS, and manual searches. The effect size
      estimates were calculated using a random-effects model. Results. The literature
      search produced 123 unique citations. One hundred sixteen records were excluded.
      The meta-analysis included seven studies (321 patients) on EEG-Biofeedback and
      EMG-Biofeedback. In comparison to control groups, biofeedback (BFB) significantly
      reduced pain intensity with a large effect size (g = 0.79; 95% CI: 0.22-1.36).
      Subgroup analyses revealed that only EMG-BFB and not EEG-BFB significantly
      reduced pain intensity in comparison to control groups (g = 0.86; 95% CI: 0.11
      1.62). BFB did not reduce sleep problems, depression, fatigue, or health-related
      quality of life in comparison to a control group. Discussion. The interpretation
      of the results is limited because of a lack of studies on the long-term effects
      of EMG-BFB in FMS. Further research should focus on the long-term efficacy of BFB
      in fibromyalgia and on the identification of predictors of treatment response. 

PMID- 24082912
TI  - Macrofollicular variant of papillary carcinoma, a potential diagnostic pitfall: A
      report of two cases including a review of literature.
AB  - Macrofollicular variant of papillary thyroid carcinoma (MFVPTC) is one of the
      rarest histologic types of papillary carcinoma. This tumor may mimic an
      adenomatoid/colloid nodule or follicular neoplasm (macrofollicular type) both on
      histology and cytology. There are very few articles describing the cytologic
      features of MFVPTC. We report the cytologic findings of two surgically confirmed
      MFVPTC. The first case showed abundant thin colloid with moderate amount of
      follicular cells arranged in a honeycombed and syncytial pattern. Some but not
      all the follicular cells showed enlarged round to ovoid nuclei, overlapping
      nuclei, few nuclear grooves and rare intranuclear inclusions. The second case
      showed abundant thin colloid and predominantly benign appearing follicular cells
      with few overlapping nuclei, enlarged round to ovoid nuclei and rare nuclear
      grooves. No intranuclear inclusions were identified. A review of the literature
      was done and the cytologic findings of MFVPTC including our two cases were
      tabulated. The cytologic findings showed moderate to abundant thin with focally
      thick colloid in 75% of cases and sheet like arrangement of follicular cells in
      76%. Although nuclear features such as chromatin clearing, overlapping and
      grooves were present in majority of cases, the quantity varied from rare to
      focal. Small to prominent nucleoli were present in all of the evaluable cases.
      Intranuclear inclusions were seen only in 45% of patients. Hence, the cytologic
      features of macrofollicular variant of papillary carcinoma though present can be
      subtle and intranuclear inclusions may not be present always. 

PMID- 24082913
TI  - Cytomorphology of unusual primary tumors in the Pap test.
AB  - Rare entities in the Pap test, which include neoplastic and non-neoplastic
      conditions, pose challenges due to the infrequent occurrence of many of these
      entities in the daily practice of cytology. Furthermore, these conditions give
      rise to important diagnostic pitfalls to be aware of in the Pap test. For
      example, cases with adenoma malignum (AM) have been called benign. Recognition of
      these conditions can help correctly interpret Pap tests as abnormal and thereby
      ensure that patients get appropriately diagnosed. In this paper, we illustrate
      and discuss selected uncommon primary neoplastic lesions of the cervix and the
      vagina that may be seen in Pap test, with a focus on cytomorphology, differential
      diagnosis and the role of possible ancillary studies. These cases include high
      grade squamous intraepithelial lesion cells with small cell morphology; small
      cell carcinoma; large neuroendocrine carcinoma; glassy cell carcinoma; AM;
      malignant mixed Mullerian tumor; clear cell carcinoma and primary malignant
      melanoma. Recognition of these rare variants/neoplasms is important so that
      involved Pap tests are not diagnosed as benign and that patients with these
      conditions get additional follow-up. 

PMID- 24082915
TI  - A semantic medical multimedia retrieval approach using ontology information
      hiding.
AB  - Searching useful information from unstructured medical multimedia data has been a
      difficult problem in information retrieval. This paper reports an effective
      semantic medical multimedia retrieval approach which can reflect the users' query
      intent. Firstly, semantic annotations will be given to the multimedia documents
      in the medical multimedia database. Secondly, the ontology that represented
      semantic information will be hidden in the head of the multimedia documents. The
      main innovations of this approach are cross-type retrieval support and semantic
      information preservation. Experimental results indicate a good precision and
      efficiency of our approach for medical multimedia retrieval in comparison with
      some traditional approaches. 

PMID- 24082914
TI  - Announcement of first time Cytojournal impact factor for 2012 coincides with
      Cytojournal decade celebration (2004-2013).

PMID- 24082916
TI  - General error analysis in the relationship between free thyroxine and thyrotropin
      and its clinical relevance.
AB  - BACKGROUND: This treatise investigates error sources in measurements applicable
      to the hypothalamus-pituitary-thyroid (HPT) system of analysis for homeostatic
      set point computation. The hypothalamus-pituitary transfer characteristic (HP
      curve) describes the relationship between plasma free thyroxine [FT4] and
      thyrotropin [TSH]. OBJECTIVE: We define the origin, types, causes, and effects of
      errors that are commonly encountered in TFT measurements and examine how we can
      interpret these to construct a reliable HP function for set point establishment.
      DESIGN AND METHODS: The error sources in the clinical measurement procedures are
      identified and analyzed in relation to the constructed HP model. RESULTS: The
      main sources of measurement and interpretation uncertainties are (1) diurnal
      variations in [TSH], (2) TFT measurement variations influenced by timing of
      thyroid medications, (3) error sensitivity in ranges of [TSH] and [FT4]
      (laboratory assay dependent), (4) rounding/truncation of decimals in [FT4] which
      in turn amplify curve fitting errors in the [TSH] domain in the lower [FT4]
      range, (5) memory effects (rate-independent hysteresis effect). CONCLUSIONS: When
      the main uncertainties in thyroid function tests (TFT) are identified and
      analyzed, we can find the most acceptable model space with which we can construct
      the best HP function and the related set point area.

PMID- 24082917
TI  - The prospects of pazopanib in advanced renal cell carcinoma.
AB  - The landscape of treatment for advanced/metastatic renal cell carcinoma (mRCC)
      has advanced significantly in the last decade and continues to evolve with the
      approval of new drugs targeting the vascular endothelial growth factor (VEGF) and
      its receptors and mammalian target of rapamycin (mTOR). Currently available oral
      VEGF tyrosine kinase inhibitors (TKIs) approved for treatment of mRCC include
      sorafenib, sunitinib, pazopanib, and axitinib. This review focuses on pazopanib,
      a multikinase VEGF TKI indicated for patients with treatment-naive and cytokine
      refractory mRCC. This article describes the preclinical and clinical evolution of
      pazopanib, with an emphasis on its development and role in mRCC. Pivotal trials
      are discussed that demonstrate the efficacy and safety of pazopanib and its
      important role in the treatment of patients with mRCC in comparison to other
      available treatment options. The clinical path of pazopanib continues to develop
      further, with several ongoing studies exploring its role in neoadjuvant and
      adjuvant RCC. Furthermore, its potential role in sequential and combination
      studies with other VEGFR and non-VEGFR targeted agents is discussed. Overall,
      pazopanib is a unique VEGF TKI, with a different and more favorable safety
      profile compared with other members of the VEGF TKI family and represents an
      attractive alternative for patients with mRCC. 

PMID- 24082918
TI  - Controversies on individualized prostate cancer care: gaps in current practice.
AB  - Prostate cancer (PCa) is a heterogeneous disease with a wide spectrum of
      aggressiveness. Evidence-based guidelines are invaluable but cannot be expected
      to be extensive enough to provide detailed guidance on the management of all
      patients. As such, the use of individualized, risk-adapted approaches to the
      management of PCa is indispensable. However, wide variation in treatment
      approaches observed for patients in practice suggests that there is an unmet need
      to improve the individualized approach towards patient care. A holistic approach
      that encompasses guidelines and evidence-based medicine could be used to guide
      individualized care for patients with PCa, from first contact through to final
      outcomes. As a result of an international expert meeting, this paper proposes
      this approach and highlights some of the factors that can be considered when
      aiming to identify patients' profiles; individualize treatment; and improve
      communication between patients and the healthcare teams. 

PMID- 24082919
TI  - Holmium laser enucleation of the prostate: a paradigm shift in benign prostatic
      hyperplasia surgery.
AB  - Holmium laser enucleation (HoLEP) was developed in the 1990s as a more efficient
      and cost effective method of benign prostatic hyperplasia surgery than laser
      vaporization and resection techniques. As a true anatomical enucleation it mimics
      open prostatectomy and is as durable. There is a significant body of level 1
      evidence in support of HoLEP, including 2 meta-analyses and 14 randomized trials
      which compare HoLEP with a number of other procedures. This review describes the
      development of and summarizes the evidence for HoLEP. 

PMID- 24082921
TI  - Study of environmental and genetic factors in children with craniosynostosis: A
      case-control study.
AB  - BACKGROUND: Craniosynostosis is a congenital defect that causes one or more
      sutures on an infant's skull to close earlier than normal. Though both genetic
      and environmental factors play a role in its pathogenesis, there is no published
      Indian data to verify this. MATERIALS AND METHODS: In this case-control study, we
      investigated the association of craniosynostosis with parental age in 50 children
      with craniosynostosis attending the surgical outpatient department of a tertiary
      care institution in North India. RESULTS: There was a significant association of
      craniosynostosis with advanced parental [OR 2.17 (95% CI 1.08 to 4.36)] but not
      maternal age. Education status of parents also revealed that those having a
      higher education had an increased risk of having a child with craniosynostosis
      [maternal education, OR 2.32 (95% CI 1.2 to 4.76); paternal education, OR 2.51
      (95% CI 1.21 to 5.0)]. Molecular analysis by sequencing confirmed following amino
      acid substitution in different Exons of the FGFR2 gene. Besides these, we found
      other novel identical mutations in FGFR2 gene in both syndromic and non-syndromic
      craniosynostoses. CONCLUSION: This is the first epidemiological study in India
      that provides evidence that, advanced paternal age and higher parental education
      level might be associated with an increased risk of craniosynostosis. New
      mutations were identified in cases of both syndromic and non-syndromic
      craniosynostosis.

PMID- 24082922
TI  - Agreement between visual and goniometric assessments of adductor and popliteal
      angles in infants.
AB  - CONTEXT: Amiel-Tison method is a commonly used technique for assessing tone and
      neurological status of infants. There is a paucity of data on the reliability of
      visual assessment of angles, a component of this method. SUBJECTS AND METHODS: We
      compared the visual and the goniometric assessment of adductor and popliteal
      angles in infants with hypertonia and neurologically normal controls. A total of
      16 infants with hypertonia and 15 normal infants underwent blinded assessment of
      the adductor and popliteal angles. STATISTICAL ANALYSIS: The mean and standard
      deviation for the difference between visual and goniometric measurements were
      calculated for popliteal and adductor angles. RESULTS: The mean differences
      between visual and goniometric measurements for the popliteal angle were 4.94
      (SD3.40) and 8.73 (SD6.10) degrees for the cases and controls respectively.
      Similarly, the values for adductor angle measurements were 8.94 (SD8.23) and
      14.47 (SD8.47) degrees respectively. CONCLUSION: The deviation of visual
      assessment from goniometric measurement was found to be less for popliteal angle
      measurement as compared to adductor angle measurements. It was note-worthy that
      the difference was less for the measurements of children with spasticity.

PMID- 24082923
TI  - Juvenile myoclonic epilepsy: Clinical characteristics, standard and quantitative
      electroencephalography analyses.
AB  - OBJECTIVES: Most studies comparing inter-ictal background quantitative
      electroencephalography (EEG) measures in generalized epilepsies with normal
      controls do not specifically determine patients with juvenile myoclonic epilepsy
      (JME) as a separate group. The study aims at comparing absolute spectral power
      and global field coherence in various frequency bands between patients diagnosed
      exclusively with JME and 10 healthy controls, and correlating significantly
      different quantitative EEG measures with various clinical characteristics and
      standard EEG abnormalities. MATERIALS AND METHODS: Clinical and EEG data were
      collected from 10 patients with JME and 10 healthy controls. Spectral power and
      global field spectral coherence were calculated using Welch's averaged
      periodogram method. The data was analyzed using descriptive statistics, Fisher's
      exact test and t-test. RESULTS: Statistically significant (or trend level) higher
      power (global alpha and theta, frontal alpha and theta, left temporal theta,
      right occipital alpha, delta and gamma1, and central delta, theta, alpha, beta,
      and gamma2) and coherence (global alpha and gamma1) was found in JME patients
      when compared to controls. Significant correlation of left frontal and central
      theta-power with presence of absence seizures (negative), central delta-, and
      theta-power with the presence of psychiatric comorbidity and central theta-power
      with frequency of myoclonic seizures was found. CONCLUSION: Findings on global
      frontal and temporal-occipital power support mild diffuse epileptogenic state and
      theta-activity as an endophenotype concepts in JME patients, respectively;
      findings suggest future studies on JME to include psychiatric comorbidity while
      selecting the sample; some spectral measures (e.g., central theta-power) do
      relate to progression of JME while some do not.

PMID- 24082924
TI  - Outcome of patients with traumatic head injury in infants: An institutional
      experience at level 1 trauma center.
AB  - BACKGROUND: Traumatic head injury is a common cause of mortality and acquired
      disability in infants and children. However, patterns and outcome of head injury
      in infants are different from other age groups. AIMS AND OBJECTIVES: Aim of our
      study was to find out epidemiological factors, characteristics of injury, and
      outcome in infants with traumatic brain injury. MATERIALS AND METHODS: This is a
      retrospective study from March 2009 through Feb 2012, at JPNATC, AIIMS, New
      Delhi. The clinical records of all patients, admitted with head injury were
      evaluated. Twenty-nine infants with traumatic brain injury were followed up and
      outcome was analyzed. RESULTS: Twenty-nine infants with traumatic brain injury
      were included in the study. Of these 17 (59%) were boys and 12 (41%) were girls.
      Fall from height was recorded in 27 (93%) patients and road traffic accident was
      the mode of injury in 2 (7%). Mild head injury (GCS 14-15) was found in 18 (62%)
      patients, moderate in 4 (14%) patients (GCS 9-13), severe (GCS 3-8) in 7 (24%)
      patients. SDH was the most common injury in 8 (27%) patients. Out of these 4
      (14%) were immediately operated, 25 (86%) were managed conservatively. Overall
      mortality was 11% (3 patients). Glasgow Outcome Scale was 5 in 20 (69%) patients
      and 3 (10.3%) patients each had GOS 3 or 4. CONCLUSION: Infants suffered
      significant brain injury due to fall. Traumatic brain injury in infants generally
      carries good outcome. Severe head injury was observed to be a predictor of poor
      outcome.

PMID- 24082925
TI  - Giant tumefactive perivascular spaces: A further case.
AB  - Virchow-Robin spaces (VRS) or the perivascular spaces are small pial lined,
      cystic structures in the brain and are filled with interstitial fluid. They are
      normal spaces, identified in all age groups and are common in places where the
      penetrating vessels enter into the substance of brain. Occasionally, these spaces
      can be enlarged and are termed as giant tumefactive perivascular spaces (GTPVS).
      When enlarged, these cysts are commonly confused with other lesions such as
      cystic neoplasms. The pathognomonic imaging appearance helps in the diagnosis of
      this condition in most instances and invasive management is unwarranted. We
      report a 4-year-old male with GTPVS. In our patient, GTPVS were diagnosed
      incidentally on brain imaging ordered for a head trauma and he was managed
      conservatively. During 1-year follow-up, he remained asymptomatic and the size of
      the cysts was virtually unchanged. 

PMID- 24082926
TI  - Primary spinal extra-osseous intradural mesenchymal chondrosarcoma in a young
      boy.
AB  - Primary spinal intradural mesenchymal chondrosarcoma is rare. We report the case
      of a 6-year-old boy to emphasize on the importance of considering this entity as
      differential diagnosis even when the lesion is purely intradural with no bony
      involvement. 

PMID- 24082927
TI  - Volume increase in craniopharyngiomas under growth hormone and/or sex hormones
      substitution: Role of tumors receptors or mere coincidence?
AB  - Craniopharyngiomas are rare embryonic tumors with low grade of malignancy that
      arise in supra-or intra-sellar areas with severe ophthalmological, neurological,
      and endocrine damages. Among pituitary deficits, somatotroph and gonadotroph
      deficiencies are the most challenging because of potential increased risk of
      tumor growth and recurrence. While data exist to suggest that growth hormone (GH)
      treatment is safe, very little is known about sex hormones replacement on tumor
      growth. Our aim was to report 3 craniopharyngiomas with tumor increase under GH
      and/or estrogen (E2) therapy. The three patients, aged 21, 22, and 23, were
      studied for severe short stature related to calcified (n = 1) or apparently
      stable (for more than 2 years) craniopharyngiomas with somatotroph and
      gonadotroph deficiencies. After 4 months to 1 year GH (n = 2) and/or E2
      replacement (n = 3), there was an increase in craniopharyngiomas' size with signs
      of intracranial hypertension in two cases. In our three craniopharyngiomas that
      were either totally calcified or stable before substitution, the tumor increase
      seemed to be the result of GH and/or E2 substitution. But, as spontaneous
      evolution of these tumors is unpredictable, we could not exclude a mere
      coincidence. 

PMID- 24082928
TI  - Atypical juvenile neuronal ceroid lipofuscinosis: A report of three cases.
AB  - The diagnosis of juvenile neuronal ceroid lipofuscinosis (JNCL) is usually based
      on age of onset, initial clinical symptoms, clinical progression, and pathologic
      findings. Our cases manifested atypical clinical symptomatology and/or pathologic
      findings and therefore, represent variant forms of JNCL. Case 1 and 2 presented
      with slow developmental regression from the age of 4 years and became blind and
      wheelchair bound at around 8 years. Pathologic finding of lymphocytes showed
      fingerprint inclusion which was consistent with JNCL. Mutational analysis was
      positive for CLN5 which usually presents as variant late infantile NCL (LINCL)
      and more common in Finnish population. Case 3 presented with progressive visual
      loss from the age of 8 years. Clinical symptomatology and age of onset were
      similar to that of JNCL but was found to have low palmitoyl protein thioesterase,
      granular inclusion body, and CLN1 mutation, thus representing milder form of
      INCL. These three cases demonstrated phenotypic-genotypic variations. Pertinent
      issues relating diagnostic difficulties, ophthalmologic, neuroradiological, and
      laboratory aspects are discussed. 

PMID- 24082920
TI  - A systematic review of the correlates and management of nonpremature ejaculatory
      dysfunction in heterosexual men.
AB  - INTRODUCTION: A better understanding of ejaculatory disorders has led to an
      increasing interest in nonpremature ejaculatory dysfunction (non-PE EjD). Current
      reviews on the subject use a symptom-based classification to describe ejaculatory
      dysfunction even when it is a single case report. While these reviews provide
      important information on the disorder, a clearer picture of the prevalence of non
      PE EjD in relation to the community and various pathophysiologic states is
      needed. OBJECTIVES: The objective of this study was to provide a systematic
      review of studies of non-PE EjD excluding single case reports. METHODS: A
      systematic review of Medline for terms including ejaculation, orgasm or
      hematospermia. Association with terms delay, pain or headache was made. The
      search was restricted to male gender and articles written in English. Abstracts
      were reviewed and those mainly concerned with premature ejaculation were
      excluded. RESULTS: A total of 333 articles on non-PE EjD were identified. The
      condition was reported in community-based studies. In certain patient
      populations, non-PE EjD was commonly reported in association with antidepressant
      and antipsychotic treatments, in patients with chronic prostatitis/chronic pelvic
      pain syndrome, patients with lower urinary tract symptoms particularly in
      association with medical or surgical treatment, patients with retroperitoneal
      surgery and in patients with neurological diseases. Few articles were concerned
      with treatment options. CONCLUSION: There is a significant prevalence of non-PE
      EjD in the community and in association with particular disease states or as a
      side effect of medical or surgical interventions. There is a need to direct
      efforts to prevent and treat these conditions.

PMID- 24082929
TI  - Pediatric anti-N methyl D aspartate receptor encephalitis.
AB  - Anti-N Methyl D Aspartate Receptor encephalitis (anti-NMDARE) is a recently
      defined disease, which is probably more under-recognized than rare. We report a
      case of anti-NMDARE in a 13-years-old girl, who presented with intractable
      seizures. To the best of our knowledge, this is the second case of pediatric anti
      NMDARE being reported from India. The need for a greater awareness of this
      disease and the subtle differences in clinical presentation between pediatric and
      adult patients are highlighted. 

PMID- 24082930
TI  - Opercular syndrome: A case report and review.
AB  - We present a 9-year-old boy with history of perinatal asphyxia and neonatal
      seizures; who presented with delayed development of speech, with predominant
      dysarthria, dysphagia, and drooling of saliva and unable to protrude tongue along
      with delayed motor and mental milestones. He had complex partial seizures since
      last 3 years requiring multiple anti-epileptic drugs. He had dysarthria, nasal
      twang, and drooling of saliva with difficulty in chewing and swallowing. Hearing
      and understanding were normal. Bilateral trigemino-facio-linguo-pharyngeal palsy
      was noticed on voluntary movements with normal jaw jerk with preserved automatic
      and emotional motor movements. Electroencephalography revealed focal left fronto
      temporal epileptiform discharges and brain imaging was suggestive of bilateral
      cortical and subcortical region encephalomalacia, predominantly involving
      bilateral opercular region. The clinical and neuroimaging features correspond to
      bilateral opercular syndrome which could have resulted from the perinatal insult
      in this case. 

PMID- 24082931
TI  - Arteriovenous malformation associated with cyst in a child: Case report and
      review of literature.
AB  - Cysts associated with arteriovenous malformations (AVMs) are either secondary to
      hemorrhage or after radiosurgery. Untreated and unruptured AVMs with large cysts
      are rare. We here describe a child with medial parietal AVM associated with cyst,
      without any history of hemorrhage or radiosurgery. Surgical excision led to cure
      for the patient. 

PMID- 24082932
TI  - Primary occipital myxoma: A rare case report.
AB  - Myxomas are benign tumors arising from mesenchymal tissues throughout the body.
      These tumors are usually seen in the atrium of heart and the jaw bone. Only a few
      cases of primary intracranial myxomas have been described in the literature. A
      rare case of primary myxoma of the occipital region is presented. A 12-year-old
      boy had mild occipital headache for the past 2 months which was unnoticed. Local
      hairdresser noticed a bulge in the occipital region while doing haircut and
      informed the parents and medical opinion was taken. He was seen by a neurosurgeon
      and after investigations he underwent craniotomy. Near total resection of the
      tumor was achieved. Histopathology and immunohistochemistry confirmed it to be a
      myxoma with no underlying cardiac focus. Following surgery the patient had rapid
      recovery. 

PMID- 24082933
TI  - Ventriculo-peritoneal shunt: A rare cause of basal ganglia and thalamic abscess.
AB  - We report an 18-month-old female child with ventriculo-peritoneal shunt related
      thalamic abscess treated with stereotactic aspiration. Deep seated abscesses are
      complex due to difficult access and are associated with an increased risk of
      intra-ventricular rupture as well as antibiotic resistance, a fact which
      justifies a more aggressive and immediate neurosurgical management. 

PMID- 24082934
TI  - Mitochondrial myopathy, encephalopathy, lactic acidosis, and stroke-like episodes
      unveiled by valproate.
AB  - Valproic acid (VPA) is widely used as an anti-epileptic drug. The primary
      mechanism of VPA toxicity is interference with mitochondrial beta-oxidation, and
      it can exacerbate an underlying mitochondrial cytopathy. We report a case of
      Mitochondrial myopathy, encephalopathy, lactic acidosis, and stroke-like episodes
      unmasked by use of Sodium Valproate in a 12-year-old boy who presented with
      headache and seizures. There was precipitation of encephalopathy, myopathy,
      lactic acidosis, and hepatic damage within two days of valproate use, after
      withdrawing of which there was a remarkable clinical and biochemical recovery. 

PMID- 24082935
TI  - Phenotypic heterogeneity in skeletal muscle sodium channelopathies: A case report
      and literature review.
AB  - Skeletal muscle sodium channelopathies (SMSCs) including hyperkalemic periodic
      paralysis (HyperPP), paramyotonia congenita (PC), and sodium channel myotonia are
      caused by sodium channel gene (SCN4A) mutations, with altered sarcolemal
      excitability, and can present as episodes of skeletal muscle weakness, paralysis,
      and myotonia. We report a teenage boy, who presented with features of HyperPP,
      PC, myotonia congenita, and sodium channel myotonia. His electromyography (EMG)
      revealed myopathic changes, myotonia, and Fournier EMG pattern I, and posed a
      diagnostic challenge. Genetic analysis showed Thr704Met mutation in SCN4A gene.
      While with typical clinical phenotypes, the electromyographic patterns can be
      used to direct genetic testing, atypical phenotypes may pose diagnostic dilemmas.
      Clinicians dealing with neuromuscular disorders in children need to be aware of
      the unusual clinical presentations of SMSC, so that focused genetic testing can
      be carried out. 

PMID- 24082936
TI  - Neuropsychological impairment in early-onset hydrocephalus and epilepsy with
      continuous spike-waves during slow-wave sleep: A case report and literature
      review.
AB  - Epilepsy with continuous spike-waves during slow-wave sleep (CSWS) is often
      characterized by a severe cognitive and behavioral impairment. Symptomatic cases
      also include patients with an early-onset hydrocephalus, but in literature
      detailed neuropsychological data on these subjects are not available. We describe
      the results of serial cognitive assessments in a girl with shunted early-onset
      hydrocephalus, followed by partial epilepsy complicated with CSWS at 4 years 10
      months, in which a dramatic cognitive and behavioral deterioration occurred few
      months after CSWS onset. Adrenocorticotropic hormone treatment improved both
      clinical and electroencephalogram picture, but an impairment of visual
      perception, visual-motor coordination and executive functions persisted after
      CSWS disappearance. We hypothesize, in this case, an involvement of right
      occipital-parietal lobe and prefrontal lobe. 

PMID- 24082937
TI  - Relapsing Devic's disease in a child.
AB  - Neuromyelitis optica (NMO) also named Devic's disease is an acute demyelinating
      disorder that primarily affects the spinal cord and optic nerves. NMO can occur
      rarely in children but pediatric NMO cases need specific consideration owing to
      possible poor visual and motor outcome. In this case report, a NMO case of a 10
      year-old girl with bilateral optic neuritis, cerebral, and spinal cord
      involvement is presented. 

PMID- 24082938
TI  - Acute longitudinal myelitis as the first presentation in child with systemic
      lupus erythematosus.
AB  - Systemic lupus erythematosus (SLE) is a multi-system auto-immune disorder that is
      characterized by widespread immune dysregulation, formation of auto-antibodies,
      and immune complexes, resulting in inflammation and potential damage to variety
      of organs. It is complicated by neurological manifestations in 25-95% of the
      patients. Acute transverse myelitis (ATM) may be a complication in 1-2% of
      patients with SLE but in some patients it may be the initial manifestation of
      SLE. This sub-group of patients where ATM is the presenting feature may not
      fulfil the ACR criteria for the diagnosis of SLE which may delay the diagnosis
      and may affect the outcome. In those patients where the involvement is more than
      four segments of the spine are believed to have poor prognosis, but early
      diagnosis and treatment may alter the course and lead to a better outcome. We
      describe a young Polish girl where ATM was the initial manifestation of SLE
      involving almost the whole length of spine but she had a reasonably good outcome
      following early diagnosis and aggressive treatment. 

PMID- 24082939
TI  - Meckel-Gruber syndrome: A rare and lethal anomaly with review of literature.
AB  - Meckel-Gruber syndrome is a rare autosomal recessive lethal malformation
      characterized by typical manifestations of occipital encephalocele, bilateral
      polycystic kidneys and post axial polydactyly. The worldwide incidence varies
      from 1 in 13,250 to 1 in 140,000 live births. Highest incidence was reported in
      Gujarati Indians. We report a rare case of Meckel-Gruber syndrome and review of
      literature. 

PMID- 24082940
TI  - Spinal extradural inclusion dermoid cyst mimicking pseudomeningocele, appearing
      after 17 years of meningomyelocele repair.
AB  - Dermoid cysts are congenital cystic tumors arising from embryonic rests and
      commonest site is in the thoracic region of the spinal canal. The authors
      reported a case of dermoid cyst in a 17-year-old boy appearing after lumbar
      meningomyelocele repair at 2 months of age. The boy presented with 6 months
      history of gradually progressive globular swelling at the site of previous scar
      and weakness of the left foot. Preoperatively small extradurally protruding
      placode was seen attached to the swelling. The swelling was completely excised.
      At 1 year follow-up patient had improvement in foot weakness with magnetic
      resonance imaging showing no residual or recurrent lesion. 

PMID- 24082941
TI  - Pediatric sciatic neuropathy presenting as painful leg: A case report and review
      of literature.
AB  - INTRODUCTION: Mononeuropathies, in general, are very uncommon in childhood.
      Sciatic neuropathy (SN) is probably underappreciated in childhood and likely to
      represent nearly one quarter of childhood mononeuropathies. MATERIALS AND
      METHODS: We present a 7-year-old girl who presented with painful right lower limb
      and abnormal gait. Detailed investigation revealed transient eosinophilia,
      abnormal neurophysiology, and magnetic resonance imaging (MRI) suggestive of
      isolated sciatic neuropathy. RESULTS: She has responded very well to
      physiotherapy and has made a complete motor recovery, although she is left with
      an area of abnormal sensation affecting the lateral border of her right leg and
      the dorsum of her foot. DISCUSSION: Differential diagnoses for pediatric SN have
      been discussed including compressive neuropathies in children and various hyper
      eosinophilia syndromes. Compressive neuropathies in childhood are very rare and
      compression of the sciatic nerve is the second most common group after peroneal
      nerve lesion.

PMID- 24082942
TI  - Extradural hematoma surgery in a child with Hutchinson-Gilford progeria syndrome:
      Perioperative concerns.
AB  - Hutchinson-Gilford progeria syndrome (HGPS) is a very rare genetic disorder
      characterized by premature ageing, severe growth failure, and very early onset
      atherosclerosis. Psychologically and emotionally child-like, these patients
      suffer from physiological changes of old age. Early and progressive
      atherosclerosis of intra-cranial vessels in HGPS patients, along with a thin skin
      and fragile vessels, make these patients susceptible to intra-cranial hematomas
      following relatively trivial injuries and to severe intra-cranial disease.
      Anesthetizing HGPS patients for surgery can be challenging due to the presence of
      a possible difficult airway, multi-system derangements, and associated skin, bone
      and joint disease. We report here one such child with HGPS who underwent
      craniotomy and evacuation of an extradural hematoma that developed after minor
      head trauma. Securing his airway during surgery was difficult. 

PMID- 24082943
TI  - Subcutaneous metastasis in medulloblastoma: A case report and review of
      literature.
AB  - Extraneural metastasis (ENM) in patients with medulloblastoma is a rare but a
      well-described phenomenon, both in children and adults. Most of the ENM involve
      bone and bone marrow and rarely involve other solid organs. Subcutaneous and
      muscular metastasis is an extremely rare event, more so in children, with only
      two cases documented in the pediatric population. We describe a case of
      medulloblastoma with ENM in right masseter and subcutaneous plane along with
      concomitant central nervous system relapse, 4 years after the primary diagnosis,
      with a brief review of the literature. 

PMID- 24082944
TI  - Terminal myelocystocele with holocord syringomyelia: Short report.

PMID- 24082945
TI  - Quadrigeminal plate cistern lipoma presenting with seizures in a child.

PMID- 24082946
TI  - "Reversible" stroke like episodes with bilateral diffusion restriction brain
      magnetic resonance imaging changes.

PMID- 24082947
TI  - Guillain-Barre syndrome presenting with severe hydrocephalus in a child.

PMID- 24082948
TI  - Arachnoid cyst with ipsilateral subdural hematoma in an adolescent - causative or
      coincidental: Case report and review of literature.

PMID- 24082949
TI  - Hydrocephalus due to aqueductal stenosis in a case of mumps meningoencephalitis:
      A rare complication.

PMID- 24082950
TI  - Misconceptions about childhood acute osteomyelitis.

PMID- 24082951
TI  - The labrum: structure, function, and injury with femoro-acetabular impingement.
AB  - BACKGROUND: The recognition of the importance of femoro-acetabular impingement
      (FAI) as a potential cause of hip pain has been stimulated by major efforts to
      salvage hip joints by reconstruction to prevent or delay the need for
      replacement. A previous review addressed the nature of FAI, the various types,
      and how to make the diagnosis. When FAI occurs, the structure between the femur
      and acetabular rim, the labrum, is initially impinged upon and subsequently
      injured. METHOD: Injury to the labrum should be recognized when treating the
      osseous causes of FAI. Preserving or recovering labral function, enhancing hip
      stability and protecting the articular surface, is critical to restoring the hip
      to normal or near-normal mechanical and physiologic function. The present review
      collected the varied essential information about the labrum in a succinct manner,
      independent of treatment algorithms. RESULTS/CONCLUSION: Advanced knowledge of
      the labrum is presented, including the anatomy, circulation, histology,
      embryology, and neurology, as well as how the labrum tears, the types of tears,
      and how to make the diagnosis. The advantages and limitations of diagnostic
      magnetic resonance techniques are discussed, including magnetic resonance imaging
      (MRI), indirect magnetic resonance arthrography (i-MRA), and direct magnetic
      resonance arthrography (d-MRA). The review recognizes the complexity of the
      labrum and provides a greater understanding of how the labrum is capable of
      stabilizing the joint and protecting the articular surface of the hip. This
      information will act as a guide in developing treatment plans when treating FAI.

PMID- 24082952
TI  - Assessment of the relationship between joint laxity and migration of the hip in
      children with Down syndrome.
AB  - PURPOSE: The aim of this cross-sectional cohort study is to describe the
      incidence of joint laxity and the correlation between joint laxity and
      radiological migration of the hip in children with Down syndrome. METHODS: Sixty
      five children (2-19 years) with Down's syndrome were examined for joint laxity.
      For each subject, laxity scores for joints were carried out with the Bulbena
      method. Plane pelvic radiographs were used to determine the migration of the hip,
      according to Reimer's migration index. RESULTS: In this study, 26 out of 65
      children with Down's syndrome (40 %) were diagnosed with general joint laxity. On
      the radiographs of the hips we found a mean Reimer's Migration Index of 5.2 % for
      all the subjects. Children with general joint laxity showed a lower Reimer's
      Migration Index (2.1 %). No significant correlation was found between general
      joint laxity and migration of the hip. CONCLUSIONS: This study showed no
      relationship between joint laxity and migration of the hip in children with
      Down's syndrome. This implicates that we were not able to prove that joint laxity
      is the major factor in developing hip migration in children with Down's syndrome.

PMID- 24082953
TI  - The role of shelf acetabuloplasty in early and late stages of Perthes disease: a
      meta-analysis of observational studies.
AB  - PURPOSE: Perthes disease may result in deformity of the proximal femoral
      epiphysis and incongruity of the hip, and shelf acetabuloplasty has been
      frequently used for treatment. The aim of this study was to review the published
      articles about the outcome of shelf acetabuloplasty as a containment or
      reconstruction-salvage procedure in Perthes disease. METHODS: We utilized the
      PubMed online database for peer review articles using the following search terms:
      shelf arthroplasty, acetabuloplasty, and Perthes. To be included in this meta
      analysis, we isolated studies on children with Perthes disease who received shelf
      acetabuloplasty as a treatment, conducted in any geographic location with the
      Stulberg classification outcome. Twenty articles were identified for a
      qualitative systematic review. The fixed effect and random effect meta-analysis
      were performed as appropriate for the summary pool estimate following the
      heterogeneity test. The meta-analysis was performed on 11 articles in three
      categories: all articles, articles for shelf arthroplasty in the early stages of
      Perthes disease, and in the late stages. RESULTS: Overall, shelf acetabuloplasty
      provided 84 % good outcome of Stulberg classes I, II, and III. Shelf
      acetabuloplasty performed in early stages for containment provided good outcome
      in 85 %, while only 69 % good outcome was achieved when shelf acetabuloplasty was
      performed in late stages for reconstruction-salvage. CONCLUSION: Shelf
      acetabuloplasty provides a good or fair Stulberg outcome when performed in early
      Perthes stages (Waldenstrom stages I and II) as a containment surgery, but less
      favorable outcomes were observed when shelf surgery was used for reconstructive
      salvage purposes in late Perthes disease stages (Waldenstrom stages III and IV).
      Caution is advised in performing the shelf procedure in children over 10-11 years
      of age.

PMID- 24082954
TI  - CT and MRI lower extremity torsional profile studies: measurement
      reproducibility.
AB  - BACKGROUND: Assessment of lower extremity (LE) torsional profile using computed
      tomography (CT) imaging is a well-recognized imaging method that supplements the
      clinical examination. Magnetic resonance imaging (MRI) is another advanced
      imaging modality that can be used as an alternative, since there are many growing
      concerns of radiation exposure with traditional CT studies, particularly in the
      skeletally immature population. METHODS: Sixty-two patients between the ages of 7
      and 19 years were included. Thirty-four had CT and 28 had MRI for assessment of
      LE torsional profile. All patients had clinical evidence of torsional
      malalignment. CT and MR images were randomized and de-identified. Two observers
      measured femoral anteversion and tibial torsion based on previously published
      methodologies. This exercise was repeated 2 weeks later and the data were
      tabulated and statistical analysis was performed. Radiation exposure for the
      patients studied by CT was estimated. RESULTS: The mean age of the patients was
      14.4 years (range 9.5-18.9 years) and 13.8 years (range 7.3-18.9 years) for the
      CT and MRI groups, respectively. Inter-observer reliability for both CT and MRI
      studies were excellent. The intra-class correlation coefficient (ICC) for femoral
      anteversion and tibial torsion studied by CT and MRI for both observers at both
      times were excellent. The radiation exposure for CT examination averaged 0.3-0.5
      mSv, compared to none with the MRI method. CONCLUSIONS: MRI provides a
      reproducible method for assessing the torsional profile in children and
      adolescents using similar anatomic landmarks for measurements as those used on CT
      torsional profile. In circumstances where MRI methods are readily available (and
      affordable), the CT torsional profile can be replaced with MRI methods, in the
      current era of growing concerns of radiation hazards and increasing awareness
      about radiation safety. LEVEL OF EVIDENCE: Diagnostic Level III.

PMID- 24082955
TI  - Quadricepsplasty for congenital dislocation of the knee and congenital quadriceps
      contracture.
AB  - PURPOSE: We encountered problems with the Curtis and Fisher technique of
      quadricepsplasty for congenital quadriceps contracture, including wound
      dehiscence, insufficient lengthening of the quadriceps and instability of the
      knee. We modified the operative technique to address these three problems. We
      undertook this study to evaluate the results of the modified technique of
      quadricepsplasty to determine if we succeeded in overcoming these limitations of
      the original technique. METHODS: Twenty children (33 knees) underwent the
      modified Curtis and Fisher quadricepsplasty through a lateral incision; a long
      tongue of the rectus femoris was raised and the vasti mobilised without dividing
      the lateral retinaculae till the collateral ligaments. The children were followed
      up for a mean period of 63 months and evaluated. The healing of the wound, active
      and passive range of motion (ROM) of the knee, the stability of the knee,
      quadriceps power and knee function were assessed. RESULTS: Primary wound healing
      occurred in 32 of 33 knees. Adequate lengthening of the quadriceps sufficient to
      facilitate knee flexion to 90 degrees  was possible. Considerable improvement in
      the ROM was noted. In non-syndromic congenital dislocation of the knee (CDK), the
      quadriceps power was Grade 5, but minor degrees of extensor lag was noted. In a
      proportion of patients, minor degrees of joint instability was present. The
      majority of children were community walkers. The overall results were better in
      non-syndromic CDK than in children with arthrogryposis, but differences of some
      variables were not significant. CONCLUSION: The modifications to the original
      Curtis and Fisher technique overcame the specific problems they were expected to
      avoid.

PMID- 24082956
TI  - Management of neglected Blount disease using double corrective tibia osteotomy
      and medial plateau elevation.
AB  - PURPOSE: A double osteotomy for correcting tibial deformity in combination with
      medial plateau elevation is recommended for the management of neglected Blount
      disease cases. We report our clinical experience with the application of this
      surgical technique and describe the long-term follow-up of the patients who were
      operated on. METHODS: During a 10-year period, eight children (8 boys) with mean
      age of 12 years (range 9-14 years) underwent surgery (9 operations) due to
      neglected infantile tibia vara. All patients suffered from stage V or VI Blount
      disease according to the Langenskiold and Riska classification. Two simultaneous
      combined osteotomies were performed for medial plateau elevation and for
      correction of the tibial deformity. The correction was immediate using K-wires
      for stabilization and a long-leg cast for immobilization. The mean duration of
      follow-up was 10 years (range 5-15 years), and the evaluations were based on
      clinical and radiological criteria. RESULTS: At the latest follow-up, there was
      no observable knee flexion or extension restriction and no signs of instability
      or lateral thrust. All patients had returned to a higher activity level. Leg
      lengthening surgery was performed in one child, but the length discrepancy was
      already present before the double osteotomy was performed. No other complications
      were noticed. All the angles measured on X-rays had been corrected, and this
      correction was retained until the latest follow-up. CONCLUSIONS: This method
      results in very good outcomes in patients who suffer from Blount disease of stage
      V or greater. With this technique, the tibial deformity is corrected, the
      articular surface is restored, and future recurrence is prevented.

PMID- 24082957
TI  - Temporal variation in pediatric supracondylar humerus fractures requiring
      surgical intervention.
AB  - BACKGROUND: Pediatric supracondylar humerus fractures commonly require surgical
      intervention and hospital admission, which is costly and consumes significant
      health care resources. There are few data regarding temporal characteristics
      (month, day and hour of injury) of this particular pediatric fracture. We wished
      to investigate the month, day of the week, and time of occurrence of these
      fractures to guide appropriate use of health care resources and prevention
      strategies. METHODS: This study was a retrospective review of clinical records
      and radiographs of 353 children with operative supracondylar humerus fractures in
      a temperate climate region over 6 years. Date and time of injury and demographic
      data (gender, age, laterality) were extracted. Variation in month, weekday, and
      time of injury was analyzed using circular analysis, cosinor analysis,
      probability distributions and topographical distribution. RESULTS: There was a
      statistically significant increase in the number of fractures during the summer
      with a peak in early July. When analyzing by month and day of the week, a peak
      was seen Thursday-Saturday during May-July and middle of the week September
      October. Weekdays demonstrated a higher proportion of fractures occurring in the
      morning and at school. The injuries occurred in the am in 37 and the pm in 241;
      detailed data were known in 227 with 37 between 0000 and 1159, 51 between 1200
      and 1559, and 139 between 1600 and 2359 h. The peak time of injury was 1800 h.
      CONCLUSIONS: The increase in supracondylar humerus fractures in the spring
      through autumn in temperate regions indicates that education campaigns
      reinforcing fall prevention and landing surfaces should be done in the early
      spring. The hourly data support the need for dedicated early morning operating
      rooms to care for these fractures. LEVEL OF EVIDENCE: Prevalence study,
      retrospective cohort, Level II .

PMID- 24082958
TI  - Application of lower extremity injury severity scores in children.
AB  - PURPOSE: Severe lower extremity trauma presents challenges in decision-making in
      terms of reconstruction or amputation. While injury severity scores have been
      developed to aid decision-making in adults, evaluation of their use in children
      is limited. METHODS: Children presenting with severe lower limb trauma from 2000
      to 2010 in a major trauma centre were identified from a trauma registry. Records
      were reviewed for details of the injury, surgical intervention, amputation and
      scores for the Mangled Extremity Severity Score, Limb Salvage Index, Predictive
      Salvage Index, Nerve injury, Ischaemia, Soft tissue injury, Skeletal injury,
      Shock, Age System and the Hanover Fracture Scale 1998. RESULTS: Twenty children
      (average age 8.7 years) were eligible for inclusion. There were three primary
      amputations and no secondary amputations. All of the scoring systems had poor
      specificity and would have recommended amputation in several limbs that were
      successfully reconstructed. CONCLUSIONS: Currently available injury severity
      scores behave differently in children and adults. In their current format, these
      scores should not be used as an absolute indication for early amputation in
      children.

PMID- 24082959
TI  - An MRI volumetric study for leg muscles in congenital clubfoot.
AB  - PURPOSE: To investigate both volume and length of the three muscle compartments
      of the normal and the affected leg in unilateral congenital clubfoot. METHODS:
      Volumetric magnetic resonance imaging (VMRI) of the anterior, lateral and postero
      medial muscular compartments of both the normal and the clubfoot leg was obtained
      in three groups of seven patients each, whose mean age was, respectively, 4.8
      months, 11.1 months and 4.7 years. At diagnosis, all the unilateral congenital
      clubfeet had a Pirani score ranging from 4.5 to 5.5 points, and all of them had
      been treated according to a strict Ponseti protocol. All the feet had
      percutaneous lengthening of the Achilles tendon. RESULTS: A mean difference in
      both volume and length was found between the three muscular compartments of the
      leg, with the muscles of the clubfoot side being thinner and shorter than those
      of the normal side. The distal tendon of the tibialis anterior, peroneus longus
      and triceps surae (Achilles tendon) were longer than normal on the clubfoot side.
      CONCLUSIONS: Our study shows that the three muscle compartments of the clubfoot
      leg are thinner and shorter than normal in the patients of the three groups. The
      difference in the musculature volume of the postero-medial compartment between
      the normal and the affected side increased nine-fold from age group 2 to 3, while
      the difference in length increased by 20 %, thus, showing that the muscles of the
      postero-medial compartment tend to grow in both thickness and length much less
      than the muscles of the other leg compartments.

PMID- 24082961
TI  - Context and the renewal of conditioned taste aversion: the role of rat dorsal
      hippocampus examined by electrolytic lesion.
AB  - An extinguished conditioned response can sometimes be restored. Previous research
      has shown that this renewal effect depends on the context in which conditioning
      versus extinction takes place. Here we provide evidence that the dorsal
      hippocampus is critically involved in the representation of context that
      underscores the renewal effect. We performed electrolytic lesions in dorsal
      hippocampus, before or after extinction, in a conditioned taste aversion paradigm
      with rats. Rats that underwent all conditioning, extinction and testing
      procedures in the same experimental context showed no renewal during testing in
      the original context. In contrast, rats that underwent extinction procedures in a
      different experimental context than the one in which they had acquired the
      conditioned response, showed a reliable renewal effect during testing in the
      original context. When electrolytic lesion was performed prior to extinction, the
      context-dependent renewal effect was disrupted. When electrolytic lesion was
      undertaken after extinction, we observed a complex pattern of data including the
      blockage of the conventional renewal effect, and the appearance of an
      unconventional renewal effect. The implications of these results are discussed
      with respect to current views on the role of the dorsal hippocampus in processing
      context information. 

PMID- 24082960
TI  - Towards a unified model of pavlovian conditioning: short review of trace
      conditioning models.
AB  - There are three basic paradigms of classical conditioning: delay, trace and
      context conditioning where presentation of a conditioned stimulus (CS) or a
      context typically predicts an unconditioned stimulus (US). In delay conditioning
      CS and US normally coterminate, whereas in trace conditioning an interval of time
      exists between CS termination and US onset. The modeling of trace conditioning is
      a rather difficult computational problem and is a challenge to the behavior and
      connectionist approaches mainly due to a time gap between CS and US. To account
      for trace conditioning, Pavlov (Conditioned reflexes: an investigation of the
      physiological activity of the cerebral cortex, Oxford University Press, London,
      1927) postulated the existence of a stimulus "trace" in the nervous system.
      Meanwhile, there exist many other options for solving this association problem.
      There are several excellent reviews of computational models of classical
      conditioning but none has thus far been devoted to trace conditioning. Eight
      representative models of trace conditioning aimed at building a prospective model
      are being reviewed below in a brief form. As a result, one of them, comprising
      the most important features of its predecessors, can be suggested as a real
      candidate for a unified model of trace conditioning. 

PMID- 24082962
TI  - Dynamic characteristics of multisensory facilitation and inhibition.
AB  - Multimodal integration, which mainly refers to multisensory facilitation and
      multisensory inhibition, is the process of merging multisensory information in
      the human brain. However, the neural mechanisms underlying the dynamic
      characteristics of multimodal integration are not fully understood. The objective
      of this study is to investigate the basic mechanisms of multimodal integration by
      assessing the intermodal influences of vision, audition, and somatosensory
      sensations (the influence of multisensory background events to the target event).
      We used a timed target detection task, and measured both behavioral and
      electroencephalographic responses to visual target events (green solid circle),
      auditory target events (2 kHz pure tone) and somatosensory target events (1.5 +/-
      0.1 mA square wave pulse) from 20 normal participants. There were significant
      differences in both behavior performance and ERP components when comparing the
      unimodal target stimuli with multimodal (bimodal and trimodal) target stimuli for
      all target groups. Significant correlation among reaction time and P3 latency was
      observed across all target conditions. The perceptual processing of auditory
      target events (A) was inhibited by the background events, while the perceptual
      processing of somatosensory target events (S) was facilitated by the background
      events. In contrast, the perceptual processing of visual target events (V)
      remained impervious to multisensory background events. 

PMID- 24082963
TI  - Bursts shape the NMDA-R mediated spike timing dependent plasticity curve: role of
      burst interspike interval and GABAergic inhibition.
AB  - Spike timing dependent plasticity (STDP) is a synaptic learning rule where the
      relative timing between the presynaptic and postsynaptic action potentials
      determines the sign and strength of synaptic plasticity. In its basic form STDP
      has an asymmetric form which incorporates both persistent increases and
      persistent decreases in synaptic strength. The basic form of STDP, however, is
      not a fixed property and depends on the dendritic location. An asymmetric curve
      is observed in the distal dendrites, whereas a symmetrical one is observed in the
      proximal ones. A recent computational study has shown that the transition from
      the asymmetry to symmetry is due to inhibition under certain conditions. Synapses
      have also been observed to be unreliable at generating plasticity when excitatory
      postsynaptic potentials and single spikes are paired at low frequencies. Bursts
      of spikes, however, are reliably signaled because transmitter release is
      facilitated. This article presents a two-compartment model of the CA1 pyramidal
      cell. The model is neurophysiologically plausible with its dynamics resulting
      from the interplay of many ionic and synaptic currents. Plasticity is measured by
      a deterministic Ca(2+) dynamics model which measures the instantaneous calcium
      level and its time course in the dendrite and change the strength of the synapse
      accordingly. The model is validated to match the asymmetrical form of STDP from
      the pairing of a presynaptic (dendritic) and postsynaptic (somatic) spikes as
      observed experimentally. With the parameter set unchanged the model investigates
      how pairing of bursts with single spikes and bursts in the presence or absence of
      inhibition shapes the STDP curve. The model predicts that inhibition strength and
      frequency are not the only factors of the asymmetry-to-symmetry switch of the
      STDP curve. Burst interspike interval is another factor. This study is an
      important first step towards understanding how STDP is affected under natural
      firing patterns in vivo. 

PMID- 24082964
TI  - Mean square stability of uncertain stochastic BAM neural networks with interval
      time-varying delays.
AB  - The robust asymptotic stability analysis for uncertain BAM neural networks with
      both interval time-varying delays and stochastic disturbances is considered. By
      using the stochastic analysis approach, employing some free-weighting matrices
      and introducing an appropriate type of Lyapunov functional which takes into
      account the ranges for delays, some new stability criteria are established to
      guarantee the delayed BAM neural networks to be robustly asymptotically stable in
      the mean square. Unlike the most existing mean square stability conditions for
      BAM neural networks, the supplementary requirements that the time derivatives of
      time-varying delays must be smaller than 1 are released and the lower bounds of
      time varying delays are not restricted to be 0. Furthermore, in the proposed
      scheme, the stability conditions are delay-range-dependent and rate
      dependent/independent. As a result, the new criteria are applicable to both fast
      and slow time-varying delays. Three numerical examples are given to illustrate
      the effectiveness of the proposed criteria. 

PMID- 24082965
TI  - Stimulus detection after interruption of the feedforward response in a backward
      masking paradigm.
AB  - In backward masking, a target stimulus is rendered invisible by the presentation
      of a second stimulus, the mask. When the mask is effective, neural responses to
      the target are suppressed. Nevertheless, weak target responses sometimes may
      produce a behavioural response. It remains unclear whether the reduced target
      response is a purely feedforward response or that it includes recurrent activity.
      Using a feedforward neural network of biological plausible spiking neurons, we
      tested whether a transient spike burst is sufficient for face categorization.
      After training the network, the system achieved face/non-face categorization for
      sets of grayscale images. In a backward masking paradigm, the transient burst
      response was cut off thereby reducing the feedforward target response. Despite
      the suppressed feedforward responses stimulus classification remained robust.
      Thus according to our model data stimulus detection is possible with purely,
      suppressed feedforward responses. 

PMID- 24082967
TI  - Editorial: current concepts and recent developments in shoulder surgery.

PMID- 24082966
TI  - Economical analysis on prophylaxis, diagnosis, and treatment of periprosthetic
      infections.
AB  - The economic burden of periprosthetic infections is enormous, but the number of
      economic studies dealing with this issue is very scarce. This review tries to
      know the economic literature existing, assess the value of current data, and
      recognize the less costly and more effective procedures for prevention, diagnosis
      and treatment of periprosthetic infections. Forty five studies meeting the
      inclusion criteria and adhering to the quality criteria used were carefully
      analyzed to extract the economic data of relevance in evaluating the magnitude of
      problem and the more cost-effective solutions. However, because the heterogeneity
      and the low-quality of most of these studies meta-analytical technique has not
      been possible. Instead, the studies have been reviewed descriptively. Optimizing
      the antibiotic use in the prevention and treatment of periprosthetic infection,
      combined with systemic and behavioral changes in the operating room; detecting
      and treating the high-risk groups; a quick, simple, reliable, safe, and cost
      effective diagnosis, and the rationale management of the instituted infection,
      specifically using the different procedures according to each particular case,
      could allow to improve outcomes and produce the highest quality of life for
      patients and the lowest economic impact. Nevertheless, the cost effectiveness of
      different interventions to prevent and to treat the periprosthetic infection
      remains unclear. 

PMID- 24082968
TI  - A history of shoulder surgery.
AB  - Shoulder surgery has emerged from being a marginalised sub-speciality to being an
      area of much research and advancement within the last seventy years. This has
      been despite the complexity of the joint, and success majorly rests on parallel
      development of biomedical technology. This article looks at the past and present
      of shoulder surgery and discusses future directions in the speciality. 

PMID- 24082970
TI  - Current concepts in anaesthesia for shoulder surgery.
AB  - There has been an exponential growth in the volume of shoulder surgery in the
      last 2 decades and a very wide variety of anaesthetic techniques have emerged to
      provide anaesthesia and post-operative analgesia. In this article we examine
      current opinion, risks, benefits and practicalities of anaesthetic practice and
      the provision of post-operative analgesia for shoulder surgery. 

PMID- 24082969
TI  - Clinical assessment of the shoulder.
AB  - The shoulder joint is complex in structure and functionality. It is often
      difficult to assess clinically due to the great variety of associated pathology.
      This article presents an overview of the anatomy of the shoulder region and
      associated pathologies, whilst providing a summary of the clinical examination of
      the shoulder and associated 'special tests'. A full history is vital when
      assessing shoulder pathology. No particular test is fully sensitive or specific
      alone and accuracy varies between both clinicians and patients alike. Assessment
      of the shoulder should be conducted systematically with a range of tests
      combined. 

PMID- 24082971
TI  - The use of shoulder hemiarthroplasty and humeral head resurfacing: a review of
      current concepts.
AB  - Since Neer's early work in the 1950s shoulder arthroplasty has evolved as a
      treatment option for various glenohumeral joint disorders. Both hemiarthroplasty
      and total shoulder prostheses have associated problems. This has led to further
      work with regards to potential resurfacing, with the aim of accurately restoring
      native proximal humeral anatomy while preserving bone stock for later procedures
      if required. Hemiarthroplasty remains a valuable treatment option in the low
      demand patient or in the trauma setting. Additional work is required to further
      define the role of humeral resurfacing, with the potential for it to become the
      gold standard for younger patients with isolated humeral head arthritis. 

PMID- 24082972
TI  - An overview of shoulder instability and its management.
AB  - The assessment and management of patients with instability of the shoulder joint
      can be challenging, due to the varying ways patients present, the array of
      different classification systems, the confusing terminology used and the
      differing potential management strategies. This review article aims to provide a
      clear explanation of the common concepts in shoulder instability and how they
      relate to the assessment and management of patients. There are sections covering
      the mechanisms of shoulder stability, the clinical assessment of patients and
      imaging techniques. Beyond that there is a discussion on the common
      classifications systems used and the typical management options. Some patients
      fall into reasonably well defined categories of classification and in these
      cases, the management plan is relatively easy to define. Unfortunately, other
      patients can elude simple classification and in these instances their management
      requires very careful consideration. Further research may help to facilitate a
      better understanding of management of the patients in this latter group. 

PMID- 24082973
TI  - The painful shoulder: shoulder impingement syndrome.
AB  - Rotator cuff disorders are considered to be among the most common causes of
      shoulder pain and disability encountered in both primary and secondary care. The
      general pathology of subacromial impingment generally relates to a chronic
      repetitive process in which the conjoint tendon of the rotator cuff undergoes
      repetitive compression and micro trauma as it passes under the coracoacromial
      arch. However acute traumatic injuries may also lead to this condition. Diagnosis
      remains a clinical one, however advances in imaging modalities have enabled
      clinicians to have an increased understanding of the pathological process.
      Ultrasound scanning appears to be a justifiable and cost effective assessment
      tool following plain radiographs in the assessment of shoulder impingment, with
      MRI scans being reserved for more complex cases. A period of observed
      conservative management including the use of NSAIDs, physiotherapy with or
      without the use of subacromial steroid injections is a well-established and
      accepted practice. However, in young patients or following any traumatic injury
      to the rotator cuff, surgery should be considered early. If surgery is to be
      performed this should be done arthroscopically and in the case of complete
      rotator cuff rupture the tendon should be repaired where possible. 

PMID- 24082974
TI  - The frozen shoulder: myths and realities.
AB  - Frozen shoulder is a common, disabling but self-limiting condition, which
      typically presents in three stages and ends in resolution. Frozen shoulder is
      classified as primary (idiopathic) or secondary cases. The aetiology for primary
      frozen shoulder remains unknown. It is frequently associated with other systemic
      conditions, most commonly diabetes mellitus, or following periods of
      immobilisation e.g. stroke disease. Frozen shoulder is usually diagnosed
      clinically requiring little investigation. Management is controversial and
      depends on the phase of the condition. Non-operative treatment options for frozen
      shoulder include analgesia, physiotherapy, oral or intra-articular
      corticosteroids, and intra-articular distension injections. Operative options
      include manipulation under anaesthesia and arthroscopic release and are generally
      reserved for refractory cases. 

PMID- 24082975
TI  - Superior labral anterior posterior lesions of the shoulder.
AB  - Superior labrum anterior and posterior (SLAP) lesion is of fairly recent
      description and its understanding is rapidly evolving. Its incidence and need for
      surgical treatment has increased exponentially in line with the increase in
      shoulder arthroscopies. It is of particular importance in the elite over head
      athlete and the young. A range of arthroscopic techniques and devices have been
      described with good functional results. The ability to return to pre injury level
      of sports remains a concern. 

PMID- 24082976
TI  - Proximal humeral fractures: a review of current concepts.
AB  - The majority of proximal humerus fractures are sustained via low energy falls in
      the elderly population. These patients can attain an acceptable level of function
      via non-operative treatment. There is yet to be a clear consensus on treatment
      options suitable for those that fall outside of this majority group. Open
      reduction internal fixation, intra medullary nailing and arthroplasty surgery
      have all been used to varying effects. Good results are achievable if
      complications such as mal-union, non-union and avascular necrosis can be avoided.
      This review aims to clarify the options available to the current day trauma
      surgeon. 

PMID- 24082978
TI  - The outcome of bone substitute wedges in medial opening high tibial osteotomy.
AB  - BACKGROUND: Opening wedge high tibial osteotomy often requires bone grafting to
      improve the union rate and avoid instability at the osteotomy site. Autograft and
      allograft have both been associated with complications and the use of bone
      substitute wedges has been advocated to improve the outcome. This study
      investigated the clinical, radiological and histological outcomes of using
      biphasic calcium phosphate ceramic (Triosite) wedges in opening wedge high tibial
      osteotomy and determined whether the presence of the graft would compromise the
      satisfactory conversion to a total knee replacement. METHODS: A consecutive
      cohort underwent radiological review to determine whether the osteotomy healed
      and the correction was maintained. Biopsies were performed on those undergoing
      second procedures. All patients converted to total knee arthroplasty were
      assessed separately as to any surgical complications attributed to the Triosite
      wedge. RESULTS: There were 36 osteotomies in 33 patients with a minimum of 4
      years follow up. All osteotomies healed. There was an average 90 (5-14) of
      correction, which was maintained. Histological assessment of 17 cases confirmed
      adequate bone replacement of the Triosite although some areas of tricalcium
      phosphate remained visible. Conversion to a total knee arthroplasty occurred in
      11 cases with no complications. CONCLUSION: Biphasic calcium phosphate ceramic
      wedges (Triosite) can be reliably used in opening wedge high tibial osteotomy
      with a low incidence of complications and satisfactory conversion to total knee
      arthroplasty.

PMID- 24082977
TI  - Reverse shoulder arthroplasty - a literature review.
AB  - Professor Grammont revolutionised shoulder surgery with his reverse shoulder
      arthroplasty design. Patients who had poor results from a conventional shoulder
      replacement because of cuff deficiency can now be treated effectively. Although
      designed for cuff tear arthropathy, indications continue to evolve and broaden.
      The initial results look very promising and the implant has gained much
      popularity over the years. The article provides an extensive literature review of
      the indications, results and complications for reverse shoulder arthroplasty. 

PMID- 24082979
TI  - NAVILAS Laser System Focal Laser Treatment for Diabetic Macular Edema - One Year
      Results of a Case Series.
AB  - PURPOSE: To report one year outcomes of focal Navigated Retina Laser Therapy
      (NAVILAS) for diabetic macular edema (DME). METHODS: Retrospective cohort series
      of 7 diabetic patients treated with NAVILAS focal laser. Statistical analysis
      included descriptive and continuous variables (Best-corrected logMAR Visual
      Acuity and time-domain optical coherence tomography (OCT) parameters) which were
      compared using a non-parametric procedure, the Friedman tests for repeated
      measures. A p-value of less than 0.05 was considered to denote statistical
      significance. RESULTS: diabetic patients (4 male; 3 female) with an average age
      of 60.8 years (range 48-85 years) were included. All treated eyes were phakic;
      patients had an average hemoglobin A1C of 9.1 (range 7.8-11.7) at baseline and
      8.0 (range 7.4-8.4) at 12 months. Six of the 7 patients had intravitreal
      bevacizumab injections prior to focal laser treatment with 1 patient having had
      more than 1 prior injection (total 3). At 12 months, median logMAR improved from
      0.695 (+/- interquartile range 0.574) to 0.477 (+/- 0.573, p <0.001). OCT median
      central foveal thickness decreased from 248 (+/- 112) to 220 um (+/- 41, p
      <0.001); total macular volume decreased from 7.84 (+/- 0.8) to 7.44 mm3 (+/- 0.7,
      p = 0.117); and largest macular subfield thickness decreased from 354 (+/- 116)
      to 289 um (+/- 42, p <0.001). All patients were treated without complications.
      CONCLUSIONS: Focal NAVILAS showed to be safe and effective in treating DME with
      improvement in visual acuity and macular edema on OCT over 12 months in this case
      series. In clinical practice, combined treatment with focal laser including
      NAVILAS and anti-vascular endothelial growth factor may provide long-term
      improvement in DME.

PMID- 24082980
TI  - Experience using the heidelberg retina angiograph 2 with a wide-field contact
      lens system in diabetic retinopathy cases.
AB  - INTRODUCTION: HRA (Heiderberg Retina Angiograph) 2 uses a confocal scanning laser
      system which can provide high quality digital images but its imaging field is
      only 30 degrees at most. HRA2 with a wide-field contact lens system allows an
      imaging field of up to 150 degrees . METHODS: We examined the advantages and
      disadvantages of HRA2, with a wide-field contact lens, for the evaluating
      diabetic retinopathy (DR). RESULTS: HRA2 was beneficial for obtaining images of
      the entire retina simultaneously, without missing peripheral retinal non
      perfusion and neovascularization. On the other hand, clear images connot be
      acquired in cases with media opacities such as corneal dystrophy, cataract and
      asteroid hyalosis, or in those with yellow tinted IOL. CONCLUSIONS: HRA2 with a
      wide-field contact lens is useful for visualizing peripheral retinal lesions in
      DR cases.

PMID- 24082981
TI  - A novel Sit4 phosphatase complex is involved in the response to ceramide stress
      in yeast.
AB  - Ceramide is a building block for complex sphingolipids in the plasma membrane,
      but it also plays a significant role in secondary signalling pathways regulating
      cell proliferation and apoptosis in response to stress. Ceramide activated
      protein phosphatase activity has been previously observed in association with the
      Sit4 protein phosphatase. Here we find that sit4Delta mutants have decreased
      ceramide levels and display resistance to exogenous ceramides and
      phytosphingosine. Mutants lacking SIT4 or KTI12 display a shift towards
      nonhydroxylated forms of long chain bases and sphingolipids, suggesting
      regulation of hydroxylase (SUR2) or ceramide synthase by Sit4p. We have
      identified novel subunits of the Sit4 complex and have also shown that known Sit4
      regulatory subunits-SAP proteins-are not involved in the ceramide response. This
      is the first observation of separation of function between Sit4 and SAP proteins.
      We also find that the Sit4p target Elongator is not involved in the ceramide
      response but that cells deficient in Kti12p-an accessory protein with an
      undefined regulatory role-have similar ceramide phenotypes to sit4Delta mutants.
      Therefore, Kti12p may play a similar secondary role in the ceramide response.
      This evidence points to a novel Sit4-dependent regulatory mechanism in response
      to ceramide stress. 

PMID- 24082983
TI  - Comparison of the Effect of Three Abutment-implant Connections on Stress
      Distribution at the Internal Surface of Dental Implants: A Finite Element
      Analysis.
AB  - Background and aims. The aim of this study was to determine the stress patterns
      within an implant and the effect of different types of connections on load
      transfer. Materials and methods. Three different types of implant-abutment
      connections were selected for this study. Sample A: 1.5-mm deep internal hex
      corresponding to a lead-in bevel; sample B: a tri-channel internal connection;
      and sample C: in-ternal Morse taper with 110 degrees of tapering and 6 anti
      rotational grooves. Four types of loading conditions were simu-lated in a finite
      element model, with the maximum von Mises stress set as output variables.
      Results. The maximum stress concentration at the inner surface of the fixtures
      was higher than the stress value in bone in all of the samples. Stress values in
      sample B were the lowest amongst all of the models. Any alterations in the amount
      and direction of the 100-N axial load resulted in an increase in fixture surfaces
      stress. Overall, the highest amount of stress (112 MPa) was detected in sample C
      at the inner surface of the fixture under a non-axial load of 300 N. Conclusion.
      Stress concentration decreased when the internal surface area increased. Creating
      three or six stops in the internal surface of the fixtures resulted in a decrease
      in stress. 

PMID- 24082984
TI  - Effect of different energy levels of microwave on disinfection of dental stone
      casts.
AB  - BACKGROUND AND AIMS: Current chemical methods may not efficiently disinfect
      dental stone casts. The aim of this study was to investigate if microwave
      irradiation is effective for disinfection of stone casts. MATERIALS AND METHODS:
      In this laboratory study, three groups (n = 162) of prepared spherical stone
      beads as carriers with a diameter of 10 mm were inoculated by separately soaking
      in three broth culture media, each containing a study microorganism-Pseudomonas
      aeruginosa, Staphylococcus aureus or Candida albicans. Six inoculated carriers
      were used for every test, including irradiation in a household microwave oven at
      300, 450, 600 or 900 W energy level, or soaking in 0.03%, 0.06%, 0.12%, 0.25% or
      0.50% concentration of sodium hypochlorite solution, at 1, 2, or 3-minute test
      times. Positive and negative control groups were considered for each test. All
      treated carriers were then individually transferred to nutrient broth culture
      medium and one milliliter from each tube was cultured in nutrient agar media over
      night. Colony forming unit per milliliter (CFU/mL) was counted, and multi-factor
      ANOVA was used to analyze data (alpha = 0.05). RESULTS: Microwave irradiation at
      600 W resulted in high-level disinfection in 3 minutes. Immersion of the stone
      casts in hypochlorite solution at 0.06% concentration resulted in disinfection
      after 2 minutes. CONCLUSION: According to the results, high level disinfection of
      the stone casts can be achieved by microwave irradiation at 600 W in 3 minutes,
      similar to a validated chemical method.

PMID- 24082985
TI  - The effects of a dairy probiotic product, espar, on salivary calcium and mutans
      streptococci.
AB  - Background and aims. Espar is a dairy product of probiotic nature that contains
      useful bacteria and high calcium content. The aim of this study was to analyze
      effects of daily consumption of Espar on the number of salivary mutans
      streptococci and the level of calcium content in a population of 15 to 17 year
      old female students. Materials and methods. A double-blind randomized crossover
      study (n = 50) of healthy female adolescents was implemented in four stage
      intervals. The first and third stages were 'run-in' and 'wash-out' intervals. For
      the second and fourth stages, two weeks long in duration, the participants
      consumed 100 grams of Espar or 200 grams of plain yogurt. At the end of each
      stage, the number of salivary mutans streptococci and the level of calcium
      content were documented. Results. There was a statistically significant decrease
      in the number of salivary mutans streptococci subsequent to Espar consumption
      when compared to ordinary yogurt (p < 0.01). Additionally, salivary calcium
      content increased significantly subsequent to the consumption of Espar and
      yogurt. However, Espar yielded a higher level of significant increase in salivary
      calcium when compared to plain yogurt (p < 0.01). Conclusion. This study found
      that daily consumption of Espar increased the salivary calcium level while
      decreasing mutans streptococci of the saliva. 

PMID- 24082982
TI  - Resilon: a comprehensive literature review.
AB  - Background and aims. An ideal root canal filling material should completely seal
      the entire root canal space and block communication between the root canal system
      and its surrounding tissues; it should also be nontoxic, noncarcinogenic, non
      genotoxic, biocompatible, insoluble in tissue fluids and dimensionally stable.
      Bonding to dentin is a promising property, which can prevent leakage and improve
      the sealing ability of root canal filling materials. Resilon was developed and
      rec-ommended initially because the existing rootcanal filling materials did not
      bond to root canal dentin. Since its introduction in 2004, numerous reports have
      been published regarding various aspects of this material. The aim of this
      literature review is to present investigations regarding Resilon's physical and
      chemical properties and leakage studies. Materials and methods. A review of the
      literature was performed by using electronic and hand searching methods for
      Resilon from May 2004 to April 2012. Results. There are many published reports
      regarding Resilon. The searchshowed that Resilon is composed of a parent polymer,
      polycaprolactone or Tone, which is a biodegradable aliphatic polyester, with
      filler particles consisting of bioactive glass, bismuth oxychloride and barium
      sulfate. It possesses some antibacterial and antifungal properties. It is a
      promising material for root canal filling. Despite the presence of numerous case
      reports and case series regarding these applications, there are few designed
      research studies on clinical applications of this material. Resilon has some
      drawbacks such as high cost. Conclusion. Resilon seals well and is a
      biocompatible material. However, more clinical studies are needed to confirm its
      efficacy compared with other materials. 

PMID- 24082986
TI  - Bond strength of composite resin to pulp capping biomaterials after application
      of three different bonding systems.
AB  - Background and aims. Bonding of composite resin filling materials to pulp
      protecting agents produces an adhesive joint which is important for the quality
      of filling as well as success of restoration. We aimed to assess the bond
      strength of composite resin to three pulp capping biomaterials: Pro Root mineral
      trioxide aggregate (PMTA), Root MTA (RMTA) and calcium enriched mixture (CEM)
      cement, using three bonding systems [a total-etch (Single Bond) and two self-etch
      systems (Protect bond and SE Bond)]. Materials and methods. Ninety acrylic molds,
      each containing a 6*2-mm hole, were divided into 3 groups and filled with PMTA,
      RMTA and CEM cements. The samples in each experimental group were then randomly
      divided into 3 sub-groups; Single Bond, Protect Bond and SE Bond bonding systems
      were applied to the tested materials. Cylindrical forms of composite resin (Z100,
      2*2 mm) were placed onto the samples and cured. Shear bond strength values were
      measured for 9 subgroups using a universal testing machine. Data were analyzed
      using two-way ANOVA. Results. The average shear bond strengths of Z100 composite
      resin after application of Single Bond, Protect Bond and SE Bond systems were as
      follows; PMTA: 5.1+/-2.42, 4.56+/-1.96 and 4.52+/-1.7; RMTA: 4.71+/-1.77, 4.31+/
      0.56 and 4.79+/-1.88; and CEM cement: 4.75+/-1.1, 4.54+/-1.59 and 4.64+/-1.78
      MPa, respectively. The type of pulp capping material, bonding system and their
      interacting effects did not have a significant effect on the bond strengths of
      composite resin to pulp capping biomaterials. Conclusion. Within the limitations
      of this in vitrostudy, bond strength of composite resin to two types of MTA as
      well as CEM cement were similar following application of the total-etch or self
      etch bonding systems. 

PMID- 24082987
TI  - Effect of Blood Contamination on Marginal Adaptation and Surface Microstructure
      of Mineral Trioxide Aggregate: A SEM Study.
AB  - BACKGROUND AND AIMS: In various clinical situations, mineral trioxide aggregate
      (MTA) may come into direct contact or even be mixed with blood. The aim of the
      present study was to evaluate the effect of exposure to blood on marginal
      adaptation and surface microstructure of MTA. MATERIALS AND METHODS: Thirty
      extracted human single-rooted teeth were used. Standard root canal treatment was
      carried out. Root-ends were resected, and retrocavities were prepared. The teeth
      were randomly divided into two groups (n = 15): in group 1, the internal surface
      of the cavities was coated with fresh blood. Then, the cavities were filled with
      MTA. The roots were immersed in molds containing fresh blood. In group 2, the
      aforementioned procedures were performed except that synthetic tissue fluid (STF)
      was used instead of blood. To assess the marginal adaptation, "gap perimeter" and
      "maximum gap width" were measured under scanning electron microscope. The surface
      microstructure was also examined. Independent samples t-test and Mann-Whitney U
      test were used to analyze the data. RESULTS: Maximum gap width and gap perimeter
      in the blood-exposed group were significantly larger than those in the STF
      exposed group (p < 0.01). In the blood-exposed group, the crystals tended to be
      more rounded and less angular compared with the STF-exposed group, and there was
      a general lack of needle-like crystals. CONCLUSION: Exposure to blood during
      setting has a negative effect on marginal adaptation of MTA, and blood-exposed
      MTA has a different surface microstructure compared to STF-exposed MTA.

PMID- 24082988
TI  - Comparison of shear bond strength of resin-modified glass ionomer and composite
      resin to three pulp capping agents.
AB  - Background and aims. Present study was designed to compare the bonding strength
      of resin-modified glass ionomer (RMGI) and composite resin to mineral trioxide
      aggregate (MTA), MTA mixed with Na2HPO4 (NAMTA), and calcium-enriched mixture
      (CEM). Materials and methods. Thirty specimens of each CEM, NAMTA, and MTA were
      prepared. Composite and RMGI restorations were then placed on the samples (15
      samples in six subgroups). Shear bond strength was assessed using universal
      testing machine. Data were analyzed with two-way ANOVA and post-hoc Tukey test.
      To compare the bond strength in subgroups, one-away ANOVA was applied.
      Significance level was set at P < 0.05. Results. Bond strength was significantly
      higher to composite samples compared to RMGI samples (p<0.001). The difference in
      bond strength of composite samples between MTA and CEM subgroups (P=0.026) as
      well as MTA and NAMTA subgroups (P= 0.019) was significant, but the difference
      between NAMTA and CEM subgroups (P=0.56) was not significant. The differences in
      bond strength in subgroups of RMGI group were not significant (P>0.05).
      Conclusion. Regarding shear bond strength to the tested substrates, composite was
      shown to be superior to RMGI. The bond of resin composite to MTA was weaker than
      that to CEM and NAMTA. 

PMID- 24082989
TI  - Relation between Oral Health Status and Electrocardiogram ST Segment Changes in a
      Group of Patients with Myocardial Infarction.
AB  - Background and aims. Only half to two-thirds of cardiovascular diseases can be
      explained by the classic risk factors. It is believed that chronic oral
      inflammation is a potent risk factor for systemic diseases. Studies show that
      electrocardiogram ST segment changes can be predictive of myocardial infarction
      outcome. In this study the relation between electrocardio-gram ST segment changes
      and oral health is evaluated. Materials and methods. In this cross-sectional
      study, thirty-six patients (14 females and 22 males) with myocardial infarction
      were enrolled. Oral health indices including DMFT index, probing depth, clinical
      attachment loss and bleeding on probing were recorded for each patient. DMFT
      index, PD, CAL as continuous variables and BOP as a categorical variable were
      compared with ST segment changes by independent t-test and chi-squared test,
      respectively (alpha=0.05). Results. DMFT index, BOP and PD revealed no
      statistically significant relation with ST segment groups. CAL showed a
      statistically significant difference within ST segment groups (P=0.003, OR=1.68).
      Conclusion. Clinical attachment loss was significantly higher in patients with ST
      segment depression, while no correla-tion was seen between probing depth,
      bleeding on probing and DMFT index with ST segment elevation or depression. 

PMID- 24082990
TI  - Multiple Calcifying Hyperplastic Dental Follicle (MCHDF): A Case Report.
AB  - Evaluation of enlarged follicles with unerupted teeth is always important because
      some changes may occur. One of the ex-tremely rare conditions seen in dental
      follicles is multiple calcifying hyperplastic dental follicle. We report a case
      of multi-ple calcifying hyperplastic dental follicle. Radiographs showed that
      mandibular third molars had a pericoronal radiolucent zone delineated by a well
      defined and sclerotic border. Microscopic examination revealed a combination of
      fibrous connec-tive and small calcifications. Multiple calcifying hyperplastic
      dental follicle is a rare condition and its correct diagnosis is necessary to
      apply appropriate treatment. 

PMID- 24082991
TI  - Osteosarcoma of the maxilla: a rare case with unusual clinical presentation.
AB  - Osteosarcoma (OS) is a malignant mesenchymal tumor, which rarely occurs in the
      maxilla. Although variable histologic and radiographic features of OS have been
      reported previously, in the majority of the cases painful swelling of the jaw is
      mentioned as the first clinical presentation. Furthermore, early diagnosis and
      wide surgical resection of the tumor are the most important determinant factors
      of prognosis. Therefore, the unusual clinical presentations of OS should be
      considered meticulously to expedite the diagnosis process. We describe a case of
      OS of the maxilla with extremely unusual presenta-tion in a 42-year-old female,
      that was initially designated as "epulis fissuratum". Here, we highlight the
      importance of com-bining the clinical, radiographic and histopathologic
      examination to obtain a definitive diagnosis and also the significance ofearly
      effective surgical intervention in evaluation of pathologic lesions. 

PMID- 24082992
TI  - Acute lymphoblastic leukemia in pregnancy: a case report with literature review.
AB  - The management of acute lymphoblastic leukemia (ALL) during pregnancy requires
      treatment with high-dose chemotherapy that can pose risks to both the mother and
      fetus. Special consideration to chemotherapy regimen and its doses and to fetal
      gestational age at the time of chemotherapy administration should be taken in
      order to limit fetal exposure while still providing optimal therapy to the
      mother. Here we describe a 22-year-old patient who was diagnosed at 26 weeks
      gestation with ALL and was treated in the third trimester with HyperCVAD
      (cytoxan, vincristine, adriamycin, dexamethasone) combination chemotherapy giving
      birth via Caesarean section to a healthy baby girl 4 weeks after induction
      chemotherapy. 

PMID- 24082993
TI  - Extracorporeal photopheresis in the treatment of graft-versus-host disease:
      evidence and opinion.
AB  - Despite significant advances in prevention and treatment strategies, graft-versus
      host disease remains the most significant cause of morbidity and nonrelapse
      mortality after allogeneic hematopoietic cellular transplantation.
      Corticosteroids remain the standard frontline therapy for graft-versus-host
      disease; however, a considerable number of patients will not respond adequately
      and others will be significantly affected by adverse effects. Extracorporeal
      photopheresis is one of several secondary therapies which have shown promise in
      the clinical setting. While the procedure itself has been around for over 20
      years, our understanding of the mechanisms from which therapeutic benefits are
      seen, and the population they are seen in, remains limited. In this article, we
      review the use of extracorporeal photopheresis for the treatment of graft-versus
      host disease including details covering the procedure's mechanism of action,
      safety profile and clinical efficacy data. 

PMID- 24082994
TI  - Hematopoietic stem-cell transplantation for sickle cell disease: current evidence
      and opinions.
AB  - With rapidly expanding evidence of benefit reported by several groups, allogeneic
      hematopoietic stem-cell transplantation has become an acceptable treatment option
      for sickle cell disease. It is currently the only curative therapy available.
      Hematopoietic stem-cell transplantation was offered primarily as a therapeutic
      option for severe sickle cell disease in the context of myeloablative matched
      sibling donor transplants over the last two decades and helped to establish the
      benefits of transplantation for this disorder. While this approach provided proof
      of principle, the disadvantages and limitations of transplantation became evident
      along the way. It has been recognized that transplantation for sickle cell
      disease does not need to adhere strictly to the principles of transplantation for
      malignant disorders, such as achievement of full donor cell chimerism. As
      reviewed here, in recent years the transplant community has set out to explore
      ways to make stem-cell transplantation more available to patients with the
      disease, define indications and better timing, and offset toxicities with novel
      approaches to conditioning and better supportive care. 

PMID- 24082996
TI  - Shining fresh light on the evolution of photosynthesis.
AB  - There are two types of photosynthesis, C3 and C4, and computational techniques
      have been used to explore how C4 plants evolved from their C3 ancestors. 

PMID- 24082995
TI  - Phenotypic landscape inference reveals multiple evolutionary paths to C4
      photosynthesis.
AB  - C4 photosynthesis has independently evolved from the ancestral C3 pathway in at
      least 60 plant lineages, but, as with other complex traits, how it evolved is
      unclear. Here we show that the polyphyletic appearance of C4 photosynthesis is
      associated with diverse and flexible evolutionary paths that group into four
      major trajectories. We conducted a meta-analysis of 18 lineages containing
      species that use C3, C4, or intermediate C3-C4 forms of photosynthesis to
      parameterise a 16-dimensional phenotypic landscape. We then developed and
      experimentally verified a novel Bayesian approach based on a hidden Markov model
      that predicts how the C4 phenotype evolved. The alternative evolutionary
      histories underlying the appearance of C4 photosynthesis were determined by
      ancestral lineage and initial phenotypic alterations unrelated to photosynthesis.
      We conclude that the order of C4 trait acquisition is flexible and driven by non
      photosynthetic drivers. This flexibility will have facilitated the convergent
      evolution of this complex trait. DOI:http://dx.doi.org/10.7554/eLife.00961.001. 

PMID- 24082998
TI  - The effect of clofibrate with phototherapy on full-term newborns with non
      hemolytic jaundice.

PMID- 24082997
TI  - Prostate cancer: current treatment and prevention strategies.
AB  - ABSTRACT: Prostate cancer is one of the life threatening disorders of male.
      Although, over the last two decades, a high rate of overdiagnosis, and
      overtreatment has lowered the incidence rate of prostate cancer, the treatment or
      prevention strategies are not enough to control the high rate of disease related
      mortality. Current medical treatment approaches include surgery, radiation
      therapy, chemotherapy, hormonal therapy, cryosurgery and other methods. These
      approaches are more or less effective either as monotherapy or in multimodal
      approach. However, many adverse or side effects exist with these strategies.
      Researches are ongoing to find out the way or better strategies to eliminate the
      adverse effects. Dietary modifications may also contribute to decrease prostate
      cancer risk. Several nutraceuticals against prostate cancer have also been
      identified. This review article summarizes some of the current treatment, and
      prevention strategies with the protection of prostate cancer, which may be
      helpful to control and prevent this highly frequent life threatening disease.

PMID- 24082999
TI  - Comparative study of tomato and tomato paste supplementation on the level of
      serum lipids and lipoproteins levels in rats fed with high cholesterol.
AB  - BACKGROUND: Hypercholesterolemia is one of the risk factors of cardiovascular
      diseases. Increased blood cholesterol affects general health and increases
      mortality due to cardiovascular disease. Poor nutrition increases LDL cholesterol
      and decreases LDL receptor activities in the liver. Scientists have shown that
      consumption of antioxidants can reduce hypercholesterolemia and proved benefits
      of fruit and vegetables. Tomato reduces oxidative stress by increasing serum
      total antioxidant level. OBJECTIVES: This study compared the tomato and tomato
      paste supplementation on the level of serum lipids and lipoproteins in rats fed
      with high cholesterol. MATERIALS AND METHODS: In this study, four male rat groups
      (10 rats per group) were used. Control group received basal diet, second group
      received basal diet and 2% cholesterol (Chol), third and fourth groups received
      basal diet, 2% cholesterol tomato and tomato paste respectively (20 percent of
      the diet) for a month. Then serum TC, LDL, HDL and TG were measured. RESULTS:
      Results showed that in Chol group, all lipids increased significantly (P < 0.05)
      except HDL compared to the control group. Tomato and tomato paste supplementation
      decreased TC, LDL and TG concentration significantly (P < 0.05) compared to Chol
      group. Tomato paste had the higher effect on lipids decreasing than tomato.
      CONCLUSIONS: Decreases of TC, LDL and TG may be related to tomato antioxidant
      effect. This course in human required more investigations.

PMID- 24083000
TI  - The supraclavicular flap for reconstruction of post-burn mentosternal
      contractures.
AB  - BACKGROUND: The thin and pliable skin of the neck is a region with
      multidirectional activity, and postburn scar contractures tend to form there
      easily. The supraclavicular flap is used to correct neck scar contractures. Its
      main vascular supply is the supraclavicular artery, and it can be harvested as
      either a skin pedicle flap or an island flap (vascular pedicle flap). OBJECTIVE:
      In this article, a total of 41 flaps are studied retrospectively and their
      efficacy in reconstruction of post-burn neck scar contractures is discussed. Also
      donor-site morbidity, patient satisfaction, and complications were evaluated.
      PATIENTS AND METHODS: Between November of 2004 and January of 2009, 41
      supraclavicular flaps were used for reconstructions in 32 patients at the
      authors' hospital. Twenty-four of these flaps were skin pedicle flaps, and 17
      were island flaps. The range of flap size was 18 +/- 6 cm in length, and 9 +/- 3
      cm in width. Pre-expansion was performed in 14 flaps. Primary closure of donor
      site was performed in 35 flaps. RESULTS: Thirty-seven of the 41 flaps survived
      completely, but there were three cases of distal necrosis (10-30%), and one case
      of complete flap necrosis. Twenty-nine of the 32 patients were satisfied with
      both the functional and aesthetic results. CONCLUSIONS: Scarring of the neck
      produces problems with function, and appearance. In our view, the supraclavicular
      flap, a thin flap of good texture, is an excellent and highly reliable flap for
      covering defects of the anterior neck. This flap is easy to harvest, with good
      functional and aesthetic results.

PMID- 24083001
TI  - Attenuation of cardiovascular responses and upper airway events to tracheal
      extubation by low dose propofol.
AB  - BACKGROUND: Hemodynamic changes and respiratory tract complications are often
      followed by tracheal extubation. These events may be dangerous in neurosurgical
      patients and those with cardiovascular disease or at an old age. OBJECTIVES: The
      aim of this study is to investigate the attenuation of cardiovascular responses
      and upper airway events resulting from tracheal extubation by low dose propofol.
      MATERIALS AND METHODS: 80 patients with ASA physical status I, undergoing an
      elective surgery in a double blind manner received 0.5mg/kg propofol or normal
      saline 2 minutes before extubation. Heart rate and blood pressure and quality of
      tracheal extubation were recorded. RESULTS: Heart rate and blood pressure in
      patients receiving propofol were less than the control group (P < 0.05) at the
      time of injection of propofol, but there were no differences between the two
      groups at the time of extubation. CONCLUSIONS: We concluded that propofol can
      reduce SBP, DBP, MAP, HR & cough production at the time of injection but there
      were no significant changes in these parameters after extubation.

PMID- 24083003
TI  - Determining and Prioritizing the Organizational Determinants of Emergency Medical
      Services (EMS) in Iran.
AB  - BACKGROUND: Improving the organization of pre-hospital emergency to provide
      emergency medical services (EMS), as a part of health system, plays an important
      role in timely and properly response to incidents, as well as, reducing
      mortalities and disabilities. OBJECTIVE: This study was conducted to determine
      the organizational determinants of emergency medical services in Iran and analyze
      their relationship and prioritize them. MATERIALS AND METHODS: The present study
      is kind of descriptive and cross-sectional study that has been conducted on the
      first half of 2010 using DEMATEL method (a group decision-making technique).
      Required data were collected using a questionnaire from a sample of 30 Iranian
      experts in pre-hospital emergency, who were selected using available sampling
      method. RESULTS: The determinants of establishing an independent EMS organization
      as a policy maker and observer organization, providing services through public
      organizations such as Emergency 115, private organizations partnership in pre
      hospital emergency system, and integrating pre-hospital and hospital emergency
      under single supervision and management were determined as organizational
      determinants. Also, establishing an independent EMS organization and integrating
      pre-hospital and hospital emergency under single supervision and management were
      determined as the most affecting and affected organizational determinants,
      respectively, with the coordinates (1.01 and 1.01) and (0.85 and - 0.85) in the
      pre-hospital emergency organizational determinants graph. CONCLUSIONS: Emergency
      medical services should be considered as a system with its independent
      components. Establishing an independent EMS organization, integrating pre
      hospital and hospital emergency under single supervision and management, as well
      as, extending the possibility of providing EMS through private sector are
      essential in order to make fundamental reforms in providing emergency medical
      services in Iran.

PMID- 24083002
TI  - The Effect of Kangaroo Mother Care (KMC) on Breast Feeding at the Time of NICU
      Discharge.
AB  - BACKGROUND: Exclusive breastfeeding is one of the most important essential
      components of Kangaroo Mother Care. OBJECTIVE: This study was performed to
      evaluate the effects of KMC on exclusive breastfeeding just at the time of
      discharge. PATIENTS AND METHODS: In this cross sectional study, 251 consecutive
      premature newborns admitted to neonatal intensive care unit (NICU) between May
      2008 and May 2009 in Alzahra University Hospital in Tabriz were evaluated. All of
      candidate mothers were educated for KMC method by scheduled program. Standard
      questionnaire was prepared by focus group discussion, and mothers filled it prior
      to infant hospital discharge. RESULTS: In this study 157(62.5%) mothers performed
      kangaroo mother care (KMC group) versus 94 (37.5%) in conventional method care
      (CMC group). In KMC group exclusive breast feeding was 98 (62.5%) vs. 34 (37.5%),
      and P =.00 in CMC group, at the time of hospital discharge. Receiving KMC, and
      gestational age were the only effective factors predicting exclusive
      breastfeeding. Our result indicated that there was a 4.1 time increase in
      exclusive breastfeeding by KMC, and also weekly increase in gestational age
      increased it 1.2 times, but maternal age, birth weight, mode of delivery, and 5
      minute Apgar score had no influence on it. CONCLUSIONS: KMC is more effective,
      and increases exclusive breast feeding successfully. It can be a good
      substitution for CMC (conventional methods of care). It is a safe, effective, and
      feasible method of care for LBWI even in the NICU settings.

PMID- 24083004
TI  - Factors Associated With Pre-hospital Delay in Patients With Acute Myocardial
      Infarction.
AB  - BACKGROUND: Treatment of patients with acute myocardial infarction (AMI) is time
      related, so delay in treatment could affect prognosis. Recognizing pre-hospital
      or in-hospital delays in initiating treatment and reducing these factors is very
      efficacious in treatment of these patients. OBJECTIVES: The aim of this study is
      evaluate the causes of pre-hospital delay just as other studies on effect of
      different variables such as socioeconomic and personal factors on pre-hospital
      delay in with patients with AMI. MATERIALS AND METHODS: A cross sectional study
      was carried out on 227 patients with acute myocardial infarction and demographic
      data, educational level, marital status, type of transfer to hospital and delay
      in arrival to hospital were recorded. RESULTS: 35.7% patients arrived during one
      hour of symptom onset, and 7.9% arrived after 24 hours. Patients having high
      level education (P = 0.0492) and with a family history of coronary artery disease
      (P = 0.01) had significantly less delay in arriving to hospital. Age, marital
      status, gender, and route of transfer to hospital were not related with pre
      hospital delay (P > 0.05). Patients thought most common cause of delay in arrival
      was unawareness of coronary artery disease (38.8%) and self-medication (34.3%).
      CONCLUSIONS: Increasing awareness of patients about cardiovascular symptoms and
      their risk factors could be helpful in patient's decision in seeking medical
      help. So general education via media and primary and middle schools could be
      helpful.

PMID- 24083005
TI  - An Outbreak of Gastroenteritis Among Iranian Pilgrims of Hajj during 2011.
AB  - BACKGROUND: Hajj is the largest annual mass gathering of muslims. The exorbitant
      crowd of pilgrims and the poor condition of personal hygiene and nutrition are
      the main predisposing factors for different infections and food poisonings.
      OBJECTIVES: This study investigates a gastroenteritis outbreak among an Iranian
      caravan of hajj pilgrims. MATERIALS AND METHODS: Studying the outbreak was
      carried out through a cohort study and it investigated the attack rates of the
      two groups of pilgrims who had consumed or had not consumed various food
      products. The relative risk and 95% confidence interval of each food product was
      then calculated. RESULTS: Only canned rice and fish had a relative risk higher
      than one, although both were not statistically significant. Therefore, it could
      be stated that the consumed foodstuffs have not caused this outbreak.
      CONCLUSIONS: None of the foodstuffs distributed among the pilgrims were the
      reason for this disease, and studying outbreaks in caravans with higher sample
      sizes is suggested.

PMID- 24083006
TI  - Quality of life and its related factors among Iranian cervical cancer survivors.
AB  - BACKGROUND: Cervical cancer is the main cause of malignancy-related death among
      women living in developing countries. OBJECTIVE: The aim of this study is to
      evaluate the quality of life (QOL) among Iranian cervical cancer survivors and
      its relationships with demographic and disease related factors. PATIENTS AND
      METHODS: A descriptive correlational study was carried out on 65 consecutive
      cervical cancer survivors in three different oncology centers related to Shahid
      Beheshti University of Medical Sciences, Tehran. The QOL was evaluated using
      three different standard questionnaires: 1) EORTC QLQ-C30 for patients with
      malignant tumors; 2) EORTC QLQ-CX24 for cervical cancer patients; and 3) SSQ for
      assessing the social support. The data was obtained by telephone interviews. The
      test-retest reliability and internal consistency of the scales were examined.
      Cronbach's alpha was calculated to assess internal consistency among items.
      Content validity was assessed to review the scales. RESULTS: Cervical cancer
      survivors stated a good QOL. However, its score was negatively associated with
      symptoms including short breathing, lack of appetite, nausea and vomiting, sleep
      disorders, peripheral neuropathy, and menopausal symptoms. Also, there was a
      positive association between QOL and economic conditions as well as QOL and
      social functioning. CONCLUSIONS: Although, the QOL in cervical cancer survivors
      was good, treatment of related symptoms can influence the QOL and improve the
      care of these patients.

PMID- 24083007
TI  - Adipose Tissue Derived Multipotent Mesenchymal Stromal Cells Can Be Isolated
      Using Serum-free Media.
AB  - BACKGROUND: Mesenchymal stromal cells (MSCs) as multipotent cells with the
      capacity to be differentiated into several cell lineages are promising sources
      for cell therapy and tissue engineering nowadays. Today most of culturing media
      are supplemented with fetal bovine serum (FBS). But FBS containing culturing
      media may raise the possibility of zoonotic infections and immunological
      reactions in cell therapy conditions. Numerous investigations have been performed
      to assess the use of FBS-free culturing systems for bone marrow derived
      mesenchymal stromal cell isolation. OBJECTIVES: The present investigation aimed
      to assess the effect of serum-free media on growth and differentiating capacity
      of adipose tissue- derived MSCs. MATERIALS AND METHODS: Approximately, 1cm3
      surgically waste sterile adipose tissue was digested with collagenase-I leading
      to a single cell suspension. The isolated cells were cultured in Ultra Culture
      media supplemented with 2% Ultroser G. MSC's isolation was confirmed with respect
      to morphology, flowcytometry, adipogenic and osteogenic differentiation
      potentials. RESULTS: The isolated cells showed adherent spindle shaped
      morphology, expanded rapidly and revealed expected MSC flowcytometric
      characteristics; they were positive for CD73, CD90, CD105, CD44, CD166, CD44 and
      negative for hematopoietic antigen such as CD45, CD34 and CD14. They could also
      be differentiated successfully into osteoblast and adipocyte, being confirmed by
      using Alizarin Red and Oil red O staining, respectively. CONCLUSIONS: According
      to the results of the present study, it can be concluded that adipose derived
      MSCs can be cultured in serum-free media with no change in their differentiating
      capacity. This finding gives us a hope for future cell therapy studies and trials
      with little concern about zoonotic infections or immunological reaction.

PMID- 24083008
TI  - Chewing sugar-free gum reduces ileus after cesarean section in nulliparous women:
      a randomized clinical trial.
AB  - BACKGROUND: Gum chewing after cesarean section may stimulate bowel motility and
      decrease duration of postoperative ileus. OBJECTIVES: The current study assessed
      the effect of chewing sugar-free gum on the return of bowel function, where
      cesarean section had been performed in nulliparous women. MATERIALS AND METHODS:
      In a randomized clinical trial, 60 patients, scheduled for cesarean section were
      randomly divided in to 2 groups gum-chewing group (n = 30) and control group (n =
      30) postoperatively. The patients in the gum-chewing group postoperatively chewed
      sugar free gum 3 times daily each time for 1 hour until discharge. The patients'
      demographic characteristics, duration of surgery, mean hunger time, flatus and
      bowel motility were compared in the two groups. RESULTS: There was no significant
      difference between the 2 groups regarding patient demographics, intraoperative,
      and postoperative care. In the gum-chewing and the control group there was a
      significant difference in the mean postoperative interval of the first bowel
      movement (20.89 +/- 8.8 versus 27.93 +/- 9.3 hours, P = 0.004), the first feeling
      of hunger (10.37 +/- 6.0 versus 16.33 +/- 9.3 hours, P = 0.005), the first
      passage of flatus (25.02 +/- 5.8 versus 31.08 +/- 9.7 hours, P = 0.003), and the
      first defecation (31.17 +/- 5.3versus 40.08 +/- 8.8 hours, P = 0.000)
      respectively, which were significantly shorter in the gum-chewing group compared
      to those of the control group. There were no major complications in either group.
      All patients in the gum-chewing group tolerated it without any major
      complications and side effects. CONCLUSIONS: The study results demonstrated that
      bowel motility after cesarean section in nulliparous women can be accelerated by
      gum chewing which is a useful, inexpensive and well-tolerated method for mothers
      in post-cesarean section.

PMID- 24083009
TI  - Application of Orthopedic Dual Sliding Compression Plate (ODSCP) in High Medial
      Tibial Open Wedge Osteotomies.
AB  - BACKGROUND: Angular deformities about the knee are one of the common disorders.
      High Tibial osteotomy is a way of correcting the deformity. Although the general
      agreement is focused toward the open wedge technique, discussion about the type
      of device is a subject to debate. OBJECTIVES: This current study has attempted to
      evaluate the results of Orthopedic Dual Sliding Compression Plate (ODSCP) in high
      medial open wedge osteotomies of the tibia. PATIENTS AND METHODS: In this cross
      sectional study, 16 patients with genuvarum undergone high medial tibial open
      wedge osteotomy and fixed by Orthopedic Dual Sliding Compression Plate. At the
      time of the last follow up visit, Lysholm score was gathered. RESULTS: The mean
      follow-up time was 9.33 +/- 1.87 month. The average age was 45.13 +/- 7.25 years.
      Three patients were male and 13 patients were female. The lysholm score showed a
      significant difference before and after surgery. CONCLUSIONS: The ODSCP has many
      advantages over the other type of plates. It can help the surgeon to operate with
      a relaxed mind and it is advisable for high tibial medial open wedge osteotomies.

PMID- 24083010
TI  - A survey on the prevalence of Chlamydia trachomatis and Mycoplasma genitalium
      infections in symptomatic and asymptomatic men referring to urology clinic of
      labbafinejad hospital, tehran, iran.
AB  - BACKGROUND: Chlamydia trachomatis and Mycoplasma genitalium infections are the
      most prevalent sexually transmitted bacterial infections in the world that cause
      urogenital infections in both men and women. It appears that infertility is a
      complication of these infections. OBJECTIVE: This study was designed to estimate
      the prevalence of Chlamydia trachomatis and Mycoplasma genitalium in symptomatic
      and asymptomatic men and to assess risk factors associated with infection.
      PATIENTS AND METHODS: Urine specimens were collected from 200 men; 100 of them
      were symptomatic and 100 asymptomatic. Samples were examined by PCR to detect the
      infections. RESULTS: C. trachomatis was detected in 20% of symptomatic and in 4%
      of asymptomatic men (P < 0.001). The prevalence of M. genitalium was revealed to
      be 12% and 2% in symptomatic and asymptomatic men, respectively (P < 0.01). Four
      of 100 men in the symptomatic group were infected with both organisms. C.
      trachomatis infection was associated with dysuria, urethral discharge, testicular
      swelling, and genital ulcer (P < 0.05). M. genitalium infection was related with
      dysuria, testis inflammation, pelvic pain and low educational level (P < 0.05).
      Furthermore, the prevalence of infections at ages 30-39 years was more than other
      ages. CONCLUSIONS: Considering the role of these bacteria in urogenital
      infections, a screening test is recommended. Since the PCR assay is a highly
      sensitive and specific assay for the detection of these bacteria in male urine
      specimens, it provides a noninvasive technique for routine screening.

PMID- 24083011
TI  - Study of the avoidable mortality in iran: kerman province.
AB  - BACKGROUND: Recognizing mortality pattern and observing its trend will help us in
      determining health priorities, allocating health resources and priorities in
      health section, eliminating main factors of premature deaths and carrying out
      epidemiological research. OBJECTIVE: The aim of this research was to determine
      avoidable mortality in Kerman province. MATERIALS AND METHODS: The present study
      was carried out longitudinal. A checklist was applied for data collection.
      Avoidable mortalities were examined in Kerman province between 2004 and 2010.
      Statistical universe of this research was all deaths registered in statistical
      unit of health deputy of Kerman University of Medical Sciences; they were all
      studied through a census method. Data analysis was carried out using descriptive
      and analytical test by SPSS18.0. RESULTS: Two thousand and one hundred -ninety
      seven deaths were examined. Of them, 210 deaths were unavoidable and 19987 were
      avoidable. In this study, most unavoidable deaths were due to pancreases cancer
      and ovary cancer. CONCLUSIONS: Relative high number of avoidable deaths indicates
      that performance of health system was not desirable in Kerman during the studied
      years. Examining trend of avoidable deaths showed that these mortalities are
      increasing although it is not significant nowadays. However, if this trend
      continues, it will be very alarming for health care authorities in this region.

PMID- 24083012
TI  - Dilatation and curettage effect on the endometrial thickness.
AB  - BACKGROUND: Endometrial receptivity is required for successful implantation and
      pregnancy. Despite the remaining controversy, many studies have shown that
      ultrasonographic endometrial thickness can be considered as an indicator of
      endometrial receptivity. OBJECTIVE: The study objective was to investigate the
      effect of dilatation and curettage on the endometrial thickness. MATERIALS AND
      METHODS: Enrolled in the study were 444 patients visited in Obstetrics &
      Gynecology clinic of Shahid Sadoughi hospital between Jan. 2011 to Sep. 2012.
      Only patients whose menstrual cycle was regular were included in study. Patients
      with myoma, adenomyosis, endometrial polyps or other uterine anomaly, those who
      smoked, whose BMI was greater than 30 and who were taking medications that could
      affect endometrial thickness were excluded. Endometrial thickness was measured
      one day before evolution (n = 444) and 5-7 days after it (n = 444) using
      transvaginal ultrasonography. The endometrial thicknesses were correlated to the
      patients' history of dilatation and curettage. Data analysis was done through
      SPSS software version 16 and using descriptive statistics, independent T-test and
      Anova. RESULTS: Endometrial thickness in patients who had 0, 1, 2, 3 and 4 D&C
      were 10.00 +/- 0.58, 9.83 +/- 0.47, 8.90 +/- 0.92, 7.42 +/- 0.18 and 7.40 +/-
      0.07, respectively one day before ovulation (spearman's correlation coefficient =
      -0.33) and 10.62 +/- 0.68, 9.64 +/- 0.49, 8.48 +/- 0.96, 6.32 +/- 0.15 and 6.90
      +/- 0.04, respectively, 5-7 days after ovulation (spearman's correlation
      coefficient = -0.66) estradiol and progesterone levels, measured in the day of
      2nd ultrasonography had not statistic relation with endometrial thickness (P =
      0.27 and 0.31). The relation of endometrial thickness and age was not significant
      (P = 0.54 and 0.06). CONCLUSIONS: Dilatation and curettage has a significant
      effect on the endometrial thinning.

PMID- 24083013
TI  - Comparison between family function dimensions and quality of life among
      amphetamine addicts and non- addicts.
AB  - BACKGROUND: One of the most important factors in drug abuse and drug avoidance is
      family and its function. OBJECTIVES: This study aimed to compare family function
      and quality of life dimensions among Amphetamine addicts and non-addicts.
      MATERIALS AND METHODS: The current study is a case-control, which assessed 95
      Iranian addicts and 95 non-addicts. Sampling method in the addicts group was
      random clustering. The non-addicts were selected from accompanied addicts in
      other centers with respect to the demographic characteristics. The instruments
      were Family Assessment and Quality of Life (SF-36) scales. SPSS software version
      11.5 was used for statistical analysis and Pearson's correlation coefficient,
      stepwise regression analysis, and independent samples t-test were conducted.
      RESULTS: The study revealed that some disorders in family function dimensions
      were higher in the addicts compared to non-addicts. Addicts have a quality of
      life lower than non-addicts (P < 0.05). There was a relationship between
      different dimensions of family function and the quality of life in both the
      addicts and non-addicts (P < 0.05). Regression analysis showed that roles
      dimensions and family function could roughly account for 17% of the changes in
      the addicts' quality of life while in the non-addicts, behavioral control
      dimension of family function could account for roughly 17% of the changes in
      their quality of life. CONCLUSIONS: Regarding the study findings, there was a
      significant difference between family function dimensions and quality of life
      among addicts and non-addicts.

PMID- 24083014
TI  - Extramedullary plasmacytoma of the nasal cavity report of three cases with review
      of the literature.
AB  - Extramedullary plasmacytoma is a rare neoplasm characterized by monoclonal
      proliferation of plasma cells. Most lesions occur in the head and neck, primarily
      in the upper aerodigestive tract. The nasal cavity and nasal septum are the most
      common sites of occurrence. In this report, three patients admitted in our clinic
      with history of nasal obstruction and/or epistaxis. Patients were diagnosed with
      extramedullary plasmacytoma and mass were completely excised. This entity usually
      occurred in 5th-6th decade of life. One of our patients, a young man, was
      completely asymptomatic and following a paroxysm of coughing, a polypoid mass was
      expectorated. The clinical and histopathologic findings of plasmacytoma are
      discussed. In order to exclude systemic involvement, systematic approach using
      clinical, laboratory, and radiologic investigations was performed. Extramedullary
      plasmacytoma of the nasal cavity is rare and should be considered in the
      differential diagnosis of nasal cavity masses especially in young age group. 

PMID- 24083015
TI  - The surgical treatment of carbuncles: a tale of two techniques.
AB  - The treatment of carbuncles is early administration of antibiotics and surgery.
      The commonest surgical approaches are saucerization, and incision and drainage
      (I&D). Although these two techniques are vastly different, there is a lack of
      evidence to determine which one produces a better outcome. Three cases of
      carbuncles are presented to illustrate the contrasting surgical techniques and
      their results. Three consecutive patients who presented to this hospital with
      carbuncles were treated with either saucerization or I&D. They were followed up
      for 8 weeks to assess their outcome. One patient had saucerization while two
      other patients underwent I&D of their carbuncles. Saucerization produced the
      shortest length of hospital stay. I&D resulted in earlier wound healing. A
      randomized controlled is needed to determine the best surgical approach for the
      treatment of carbuncles. 

PMID- 24083016
TI  - Oral health status in three long term care units of schizophrenic patients in
      chaharmahal-bakhtiari province, iran.

PMID- 24083017
TI  - Anesthetic management of patients with anterior mediastinal masses undergoing
      chamberlain procedure (anterior mediastinostomy).

PMID- 24083018
TI  - Acute pulmonary edema due to excessive water intake in pyschiatric patient.

PMID- 24083019
TI  - Radiographic Outcome of Surgical Treatment of Scheuermann's Kyphosis: a
      Comparative Study Between Old and New Spinal Instruments.

PMID- 24083020
TI  - Prevalence of HBV in HIV Patients Referred to Imam Khomeini Hospital, Tehran,
      Iran from 2008-2010.

PMID- 24083021
TI  - Examining a ripple effect: do spouses' behavior changes predict each other's
      weight loss?
AB  - BACKGROUND: Including spouses in obesity treatment has been found to promote
      weight loss. We assessed whether spouses' diet and activity changes impacted each
      other's weight loss when both members attended an active weight loss program
      (TOGETHER) or only the primary participant attended treatment (ALONE). METHODS:
      Heterosexual couples (N = 132) enrolled in an 18-month randomized controlled
      weight loss trial were weighed and completed measures of dietary intake and
      physical activity at baseline and 6 months. We conducted dyadic data analyses
      using the Actor-Partner Interdependence Model. RESULTS: Participants' weight loss
      was not predicted by their partners' behavior changes. However, partners' weight
      loss was predicted by their participants' changes in calorie and fat intake. When
      partners were coupled with a participant who did not reduce their own calorie and
      fat intake as much, these partners had higher weight loss when treated in the
      TOGETHER group but lower weight loss when they were untreated in the ALONE group.
      There were no reciprocal effects found with physical activity changes.
      CONCLUSIONS: Direct treatment had the greatest impact on participants and
      partners who were treated. Untreated partners' weight losses were positively
      impacted by their spouses' dietary changes, suggesting a ripple effect from
      treated spouses to their untreated partners.

PMID- 24083022
TI  - Tryptophan-kynurenine metabolism and insulin resistance in hepatitis C patients.
AB  - Chronic hepatitis C virus (HCV) infection is associated with 50% incidence of
      insulin resistance (IR) that is fourfold higher than that in non-HCV population.
      IR impairs the outcome of antiviral treatment. The molecular mechanisms of IR in
      HCV are not entirely clear. Experimental and clinical data suggested that
      hepatitis C virus per se is diabetogenic. However, presence of HCV alone does not
      affect IR. It was proposed that IR is mediated by proinflammatory cytokines,
      mainly by TNF-alpha. TNF-alpha potentiates interferon-gamma-induced
      transcriptional activation of indoleamine 2,3-dioxygenase, the rate-limiting
      enzyme of tryptophan- (TRP-) kynurenine (KYN) metabolism. Upregulation of TRP-KYN
      metabolism was reported in HCV patients. KYN and some of its derivatives affect
      insulin signaling pathways. We hypothesized that upregulation of TRP-KYN
      metabolism might contribute to the development of IR in HCV. To check this
      suggestion, we evaluated serum concentrations of TRP and KYN and HOMA-IR and HOMA
      beta in 60 chronic HCV patients considered for the treatment with IFN-alpha. KYN
      and TRP concentrations correlated with HOMA-IR and HOMA-beta scores. Our data
      suggest the involvement of KYN and its metabolites in the development of IR in
      HCV patients. TRP-KYN metabolism might be a new target for prevention and
      treatment of IR in HCV patients. 

PMID- 24083023
TI  - Predictors of better self-care in patients with heart failure after six months of
      follow-up home visits.
AB  - This study aimed to examine the predictors of better self-care behavior in
      patients with heart failure (HF) in a home visiting program. This is a
      longitudinal study nested in a randomized controlled trial (ISRCTN01213862) in
      which the home-based educational intervention consisted of a six-month followup
      that included four home visits by a nurse, interspersed with four telephone
      calls. The self-care score was measured at baseline and at six months using the
      Brazilian version of the European Heart Failure Self-Care Behaviour Scale. The
      associations included eight variables: age, sex, schooling, having received the
      intervention, social support, income, comorbidities, and symptom severity. A
      simple linear regression model was developed using significant variables (P <=
      0.20), followed by a multivariate model to determine the predictors of better
      self-care. One hundred eighty-eight patients completed the study. A better self
      care behavior was associated with patients who received intervention (P < 0.001),
      had more years of schooling (P = 0.016), and had more comorbidities (P = 0.008).
      Having received the intervention (P < 0.001) and having a greater number of
      comorbidities (P = 0.038) were predictors of better self-care. In the
      multivariate regression model, being in the intervention group and having more
      comorbidities were a predictor of better self-care. 

PMID- 24083024
TI  - Fully endoscopic microvascular decompression: our early experience.
AB  - Background. Microvascular decompression (MVD) is a widely accepted treatment for
      neurovascular disorders associated with facial pain and spasm. The endoscope has
      rapidly become a standard tool in neurosurgical procedures; however, its adoption
      in lateral approaches to the posterior fossa has been slower. The endoscope is
      used primarily to assist conventional microscopic techniques. We are interested
      in developing fully endoscopic approaches to the cerebellopontine angle, and
      here, we describe our preliminary experience with this procedure for MVD.
      Methods. A retrospective review of our two-year experience from 2011 to 2012,
      transitioning from using conventional microscopic techniques to endoscope
      assisted microsurgery to fully endoscopic MVD, is provided. We also reviewed our
      preliminary outcomes during this transition. Results. There was no difference in
      the surgical duration of these three procedures. In addition, the majority of
      procedures performed in 2012 were fully endoscopic, suggesting the ease of
      incorporating this solo tool into practice. Pain outcomes of fully endoscopic MVD
      appear to be very similar to those of both conventional and endoscope-assisted
      MVDs. Complications occurred in all groups at equally low rates. Conclusion.
      Fully endoscopic MVD is both safe and effective. By enhancing visualization of
      structures within the cerebellopontine angle, endoscopy may prove to be a
      valuable adjunct or alternative to conventional microscopic approaches. 

PMID- 24083025
TI  - Female gender remains an independent risk factor for poor outcome after acute
      nontraumatic intracerebral hemorrhage.
AB  - Objective. To study whether gender influences outcome after intracerebral
      hemorrhage (ICH). Methods. Cohort study of 245 consecutive adults presenting to
      the emergency department with spontaneous ICH from January 2006 to December 2008.
      Patients with subarachnoid hemorrhage, extradural hemorrhage, and recurrence of
      hemorrhage were excluded. Results. There were no differences noted between
      genders in stroke severity (NIHSS) at presentation, ICH volume, or
      intraventricular extension (IVE) of hemorrhage. Despite this, females had 1.94
      times higher odds of having a bad outcome (modified Rankin score (mRs) >=3) as
      compared to males (95% CI 1.12 to 3.3) and 1.84 times higher odds of early
      mortality (95% CI 1.02-3.33). analyzing known variables influencing mortality in
      ICH, the authors found that females did have higher serum glucose levels on
      arrival (P = 0.0096) and 4.2 times higher odds for a cerebellar involvement than
      males (95% CI 1.63-10.75). After adjusting for age, NIHSS, glucose levels,
      hemorrhage volume, and IVE, female gender remained an independent predictor of
      early mortality (P = 0.0127). Conclusions. Female gender may be an independent
      predictor of early mortality in ICH patients, even after adjustment for stroke
      severity, hemorrhage volume, IVE, serum glucose levels, and age. 

PMID- 24083026
TI  - Alzheimer's disease clinical and research update for health care practitioners.
AB  - Of the approximately 6.8 million Americans who have been diagnosed with dementia,
      over 5 million have been diagnosed with Alzheimer's Disease (AD). Due to the rise
      in the aging population, these figures are expected to double by 2050. The
      following paper provides an up-to-date review of clinical issues and relevant
      research. Research related to the methods of the earliest possible detection of
      AD is ongoing. Health care professionals should play a critical role in
      differentially diagnosing AD patients, as well as supporting their families.
      Novel interventions, including medications, natural supplements, and behavioral
      techniques, are constantly appearing in the literature. It is necessary for the
      health practitioner to remain current, regarding AD, as such information will
      facilitate better care for patients and their families. 

PMID- 24083027
TI  - The Effects of Acupuncture Treatment on Sleep Quality and on Emotional Measures
      among Individuals Living with Schizophrenia: A Pilot Study.
AB  - Purpose. To examine the effects of acupuncture on sleep quality and on emotional
      measures among patients with schizophrenia. Methods. Twenty patients with
      schizophrenia participated in the study. The study comprised a seven-day running
      in no-treatment period, followed by an eight-week experimental period. During the
      experimental period, participants were treated with acupuncture twice a week.
      During the first week (no-treatment period) and the last week of the experimental
      period, participants filled out a broad spectrum of questionnaires and their
      sleep was continuously monitored by wrist actigraph. Results. A paired-sample t
      test was conducted comparing objective and subjective sleep parameters manifested
      by participants before and after sequential acupuncture treatment. A significant
      effect of acupuncture treatment was observed for seven objective sleep variables:
      sleep onset latency, sleep percentage, mean activity level, wake time after sleep
      onset, mean number of wake episodes, mean wake episode and longest wake episode.
      However, no significant effects of acupuncture treatment were found for
      subjective sleep measures. Likewise, the results indicate that acupuncture
      treatment improved psychopathology levels and emotional measures, that is,
      depression level and anxiety level. Conclusions. Overall, the findings of this
      pilot study suggest that acupuncture has beneficial effects as a treatment for
      insomnia and psychopathology symptoms among patients with schizophrenia. 

PMID- 24083028
TI  - Loss of villin immunoexpression in colorectal carcinoma is associated with poor
      differentiation and survival.
AB  - Background and Aims. Villin is a highly specialised protein and is expressed in
      intestinal and renal proximal tubular epithelium. It was detected in colorectal
      carcinomas (CRC) and other nongastrointestinal tumours. The aim of the current
      study is to investigate the immunohistochemical expression of villin in a subset
      of primary CRC and determine its relation to tumour differentiation, invasion,
      nodal metastasis, recurrence, and disease-free survival. Patients and Methods.
      Paraffin blocks of 93 cases of CRC were retrieved constituting 93 primary CRC and
      58 adjacent normal mucosa. Immunohistochemistry was performed using antivillin
      antibody. The extent (%) of villin immunoexpression was categorised for
      statistical analysis. Statistical tests were used to determine the association of
      villin with clinicopathological characteristics: age, sex, tumour location,
      tumour size, depth of invasion, tumour grade, nodal metastasis, lymphovascular
      invasion, margin status, recurrence, and survival. Results. Villin immunostaining
      results showed that villin is downregulated in CRC. Villin has no association
      with age, sex, tumour location, depth of invasion, nodal metastasis,
      lymphovascular invasion, margin status, and recurrence. However, villin is
      expressed in higher rate in CRC less than 5 cm, well- and moderately
      differentiated CRC. Poor survival was associated with tumour with low villin
      immunoexpression. Conclusion. Villin was downregulated in CRC. Villin
      immunoexpression in CRC is associated with better survival, well-differentiated
      tumours, and small-sized tumours. Villin has no significant association with
      disease recurrence or nodal metastasis. More in vivo and in vitro studies are
      required for further elucidation of how villin may be involved in CRC. 

PMID- 24083029
TI  - HBsAg Positive Patient Characteristics in Hospital and Blood Donation Camps.
AB  - Background. Prevention of the residual risk of transfusion transmitted hepatitis
      B virus infection (HBV) is mostly dependant on serological screening of blood
      donors for HBsAg and antibody to hepatitis B core antigen (anti-HBc Ab). This
      study aimed to study the prevalence of HBsAg and anti-HBc Ab and to compare the
      profile of blood donors attending a blood donation camp and people attending a
      hospital based camp. Methods. In the blood donor camp, all the blood units were
      screened for HBV, (HBsAg and anti-HBc), and in the hospital based camp, screening
      was done for HBsAg alone. Baseline demographic characteristics were noted.
      Results. The number of blood bank donors was 363 (47.5%) and hospital camp
      attendees was 402 (52.5%). Prevalence of HBsAg positivity was similar in both the
      groups at 1.7% and 1.9%, respectively. Anti-HBc Ab positivity (Total) was 6%
      among the blood donors; Overall prevalence of HBV infection in this group was
      3.2%. Conclusion. Policy for checking the collected blood unit by 3 tests for
      anti-HBc, anti-HBsAb, and HBsAg should be reconsidered to possibly achieve the
      zero risk goal of transfusion transmitted HBV infection. Blood obtained from a
      vaccinated donor may give an added protection to the recipient. 

PMID- 24083030
TI  - Midkine Mediates Intercellular Crosstalk between Drug-Resistant and Drug
      Sensitive Neuroblastoma Cells In Vitro and In Vivo.
AB  - Resistance to cytotoxic agents has long been known to be a major limitation in
      the treatment of human cancers. Although many mechanisms of drug resistance have
      been identified, chemotherapies targeting known mechanisms have failed to lead to
      effective reversal of drug resistance, suggesting that alternative mechanisms
      remain undiscovered. Previous work identified midkine (MK) as a novel putative
      survival molecule responsible for cytoprotective signaling between drug-resistant
      and drug-sensitive neuroblastoma, osteosarcoma and breast carcinoma cells in
      vitro. In the present study, we provide further in vitro and in vivo studies
      supporting the role of MK in neuroblastoma cytoprotection. MK overexpressing wild
      type neuroblastoma cells exhibit a cytoprotective effect on wild type cells when
      grown in a co-culture system, similar to that seen with doxorubicin resistant
      cells. siRNA knockdown of MK expression in doxorubicin resistant neuroblastoma
      and osteosarcoma cells ameliorates this protective effect. Overexpression of MK
      in wild type neuroblastoma cells leads to acquired drug resistance to doxorubicin
      and to the related drug etoposide. Mouse studies injecting various ratios of
      doxorubicin resistant or MK transfected cells with GFP transfected wild type
      cells confirm this cytoprotective effect in vivo. These findings provide
      additional evidence for the existence of intercellular cytoprotective signals
      mediated by MK which contribute to chemotherapy resistance in neuroblastoma. 

PMID- 24083031
TI  - DPOAE Intensity Increase at Individual Dominant Frequency after Short-Term
      Auditory Exposure.
AB  - Previous experiments suggested the possibility of a short-term sound stimulus
      evoked and transient increase in DPOAE amplitudes. This phenomenon is possibly
      due to the complexity of the outer hair cells and their efferent control system
      and the different time scales of regulatory processes. A total of 100 healthy
      subjects ranging from 18 to 40 years of age with normal hearing and normal DPOAE
      values in the range of 781-4000 Hz were recruited in the study. Diagnostic DPOAE
      measurements were performed after short-term sound exposure. We proposed a 10
      sec, 50 dB sound impulse as the most effective stimulus for clinical practice
      between 40 and 60 sec poststimulus time to detect the aforementioned transient
      DPOAE increase. We developed a procedure for detection of this transient increase
      in DPOAE by the application of a short-term sound exposure. The phenomenon was
      consistent and well detectable. Based on our findings, a new aspect of cochlear
      adaptation can be established that might be introduced as a routine clinical
      diagnostic tool. A mathematical model was provided that summarizes various
      factors that determine electromotility of OHCs and serves as a possible clinical
      application using this phenomenon for the prediction of individual noise
      susceptibility. 

PMID- 24083032
TI  - Biomonitoring and Elimination of Perfluorinated Compounds and Polychlorinated
      Biphenyls through Perspiration: Blood, Urine, and Sweat Study.
AB  - Perfluorinated compounds (PFCs) are man-made organofluorine chemicals
      manufactured and marketed for their stain-resistant properties. Polychlorinated
      biphenyls (PCBs) are anthropogenic organochlorine compounds previously used in
      various industrial and chemical applications prior to being banned in the Western
      world in the 1970s. Both PFCs and PCBs are persistent contaminants within the
      human organism and both have been linked to adverse health sequelae. Data is
      lacking on effective means to facilitate clearance of PFCs and PCBs from the
      body. Methods. Blood, urine, and sweat were collected from 20 individuals (10
      healthy participants and 10 participants with assorted health problems) and
      analyzed for PFCs and PCBs using high performance liquid chromatography tandem
      mass spectrometry. Results. Some individual PCB congeners, but not all, were
      released into sweat at varying concentrations. None of the PFCs found in serum
      testing appeared to be excreted efficiently into perspiration. Conclusions.
      Induced perspiration may have some role in facilitating elimination of selected
      PCBs. Sweat analysis may be helpful in establishing the existence of some accrued
      PCBs in the human body. Sweating does not appear to facilitate clearance of
      accrued PFHxS (perfluorohexane sulfonate), PFOS (perfluorooctane sulfonate), or
      PFOA (perfluorooctanoic acid), the most common PFCs found in the human body. 

PMID- 24083033
TI  - Early correction of malocclusion using planas direct tracks.
AB  - The correction of functional posterior crossbite through Planas Direct Tracks has
      many characteristics that can become advantages. The aim of this study was to
      present a clinical case showing how to use this procedure for early correction
      with resources available through public health services. The patient, a 4-year
      old girl, arrived to receive treatment due to a functional unilateral crossbite.
      When the mandible was moved to the centric position, it was observed that the
      teeth had occlusal trauma. An occlusal adjustment was performed. The adjustment
      was not sufficient to promote functional equilibrium; thus, Planas Direct Tracks
      were made, resulting in functional equilibrium and correction of the
      malocclusion. As shown in the case report, the Planas Direct Tracks were
      effective for the correction of the posterior crossbite. If malocclusion is
      considered a public health problem, implementation of low-cost and easy-to
      execute techniques is needed. 

PMID- 24083034
TI  - Computer guided implantology accuracy and complications.
AB  - The computer-based method allows the computerized planning of a surgical
      implantology procedure, using computed tomography (CT) of the maxillary bones and
      prosthesis. This procedure, however, is not error-free, unless the operator has
      been well trained and strictly follows the protocol. A 70-year-old woman whom was
      edentulous asked for a lower jaw implant-supported prosthesis. A computer-guided
      surgery was planned with an immediate loading according to the NobelGuide
      technique. However, prior to surgery, new dentures were constructed to adjust the
      vertical dimension. An interim screwed metal-resin prosthesis was delivered just
      after the surgery; however, after only two weeks, it was removed because of a
      complication. Finally, a screwed implant bridge was delivered. The computer
      guided surgery is a useful procedure when based on an accurate 3D CT-based image
      data and an implant planning software which minimizes errors. 

PMID- 24083036
TI  - Florid cementoosseous dysplasia: a rare case report.
AB  - Florid cementoosseous dysplasia (FCOD) is a rare, benign, fibroosseous, and
      multifocal dysplastic lesion of the jaw that consists of cellular fibrous
      connective tissue with bone and cementum-like tissue. FCOD is most commonly found
      in middle-aged black women, is generally asymptomatic, and is usually detected
      during radiological examination. FCOD associated with multiple impacted teeth and
      bone expansion is a very rare phenomenon, and there are only a few familial cases
      reported in the literature. In this report, a 35-year-old male Turkish patient is
      presented who was diagnosed with nonfamilial FCOD from clinical, radiological,
      and histopathological findings. To our knowledge this is the first case of the
      nonfamilial FCOD with this many impacted teeth and severely expanded bones. 

PMID- 24083035
TI  - Melanotic neuroectodermal tumor of infancy in the maxilla.
AB  - Melanotic neuroectodermal tumors of infancy (MNTIs) are rare fast-growing tumors
      with high recurrence rates. These tumors, which originate in the neural crest,
      commonly occur in the anterior maxilla of children under the age of one. Here, we
      describe an MNTI case in a two-month-old girl with increasing swelling in the
      left cheek. MNTI was diagnosed in this case following tomography and biopsy. The
      patient's histological and immunohistochemical profile indicated a remarkable
      combination of neural, melanocytic, and epithelial cell differentiation. One year
      following tumor excision, a follow-up examination revealed that the child
      exhibited no tumor recurrence. Approximately 260 cases of MNTI have been reported
      since this type of tumor was first described. In the present case, early
      diagnosis minimized the difficulties and risks associated with treatment and
      facilitated an optimal outcome. Despite complete surgical excision, careful
      followup is recommended. In addition, maxillary functional orthopedics and
      reconstruction may be necessary in cases of MNTI. 

PMID- 24083037
TI  - Lyme carditis in an immunocompromised patient.
AB  - We present a case of a 68-year-old man with a history of liver transplant and of
      chronic immunosuppression therapy who presented to the emergency department (ED)
      for fevers and worsening fatigue for two days. On further investigation, the
      patient was found to have a new first-degree heart block on his
      electrocardiograph. Coupled with the history of a recent tick bite, the patient
      was diagnosed with vector-borne carditis. Although the patient's titers for
      various vectors remained negative, due to a long history of immunosuppression, he
      was treated for Lyme disease and his heart block completely resolved with
      antibiotic treatment. We describe details of the case as well as discuss the
      impacts of immunosuppression on vector-borne disease. Immunosuppressed patients
      represent a special population and can present with chief complaints made even
      more complicated by their medical history, and this case illustrates the
      importance of being mindful of how immunosuppression can affect a patient's
      presentation. As the efficacy of antirejection medications improved, the ED may
      see an increasing number of patients with solid organ transplants. A greater
      understanding of this special patient population is key to formulating optimal
      treatment plans. 

PMID- 24083038
TI  - Cotrimoxazole-induced hypoglycaemia in a patient with churg-strauss syndrome.
AB  - Cotrimoxazole is a commonly used antimicrobial agent which is traditionally
      indicated in the management of pneumocystis infection of which HIV and
      immunosuppressed individuals are at high risk. Furthermore, it can be used on the
      long term for prophylactic indications. Hypoglycaemia following commencement of
      cotrimaoxazole is a rare adverse effect which was first described in 1988. We
      describe a case of hypoglycaemia shortly following initiation of cotrimoxazole
      indicated as long-term prophylaxis on a background of Churg-Strauss syndrome. The
      patient was symptomatic for hypoglycaemia despite simultaneous use of high-dose
      prednisolone; however, the hypoglycaemia did not require a hospital admission. We
      will explore the risk factors, monitoring requirements, and the mechanism by
      which co-trimoxazole induces hypoglycaemia. 

PMID- 24083039
TI  - A male with cooccurrence of down syndrome and fragile x syndrome.
AB  - Down syndrome is the most common identifiable genetic cause of intellectual
      disability, with a unique physical gestalt that makes diagnosis possible during
      the newborn period. However, the physical characteristics of Fragile X syndrome
      are fairly subtle, resulting in the first clinical suspicion often arising from
      delayed developmental milestones. In addition, maladaptive behavior and autistic
      like tendencies, such as hand flapping, poor eye contact, and hand biting, may be
      noted in Fragile X syndrome but are not as commonly observed in Down syndrome.
      Recognition of a potential secondary diagnosis, such as Fragile X syndrome, in
      individuals with Down syndrome is critical because there have been advances in
      targeted pharmacologic treatments for both conditions. Thus, an accurate
      diagnosis has implications in improving the individual's quality of life. 

PMID- 24083040
TI  - A puzzle of hemolytic anemia, iron and vitamin B12 deficiencies in a 52-year-old
      male.
AB  - A 52-year-old male with no significant past medical history reports increasing
      generalized fatigue and weakness for the past 2 weeks. Physical examination
      reveals jaundice and pallor without organomegaly or lymphadenopathy. His
      hemoglobin was 5.9 g/dL with a mean corpuscular volume of 87.1 fL and elevated
      red blood cell distribution width of 30.7%. His liver function test was normal
      except for elevated total bilirubin of 3.7 mg/dL. Serum LDH was 701 IU/L, and
      serum haptoglobin was undetectable. Further investigation revealed serum vitamin
      B12 of <30 pg/mL with elevated methylmalonic acid and homocysteine level. In
      addition, serum ferritin and transferrin saturation were low. The patient was
      diagnosed with hemolytic anemia secondary to vitamin B12 deficiency with
      concomitant iron deficiency anemia. 

PMID- 24083041
TI  - Pemphigoid gestationis after spontaneous expulsion of a massive complete
      hydatidiform mole.
AB  - Pemphigoid gestationis (PG) is a rare, perinatal, autoimmune, and blistering
      dermatosis. Only few cases of PG involving hydatidiform moles have been reported.
      Complete hydatidiform moles are usually evacuated by dilatation and curettage. We
      report a patient with a massive complete hydatidiform mole that underwent
      spontaneous expulsion; she subsequently developed PG. A 19-year-old unmarried
      nulligravid woman was referred to our hospital following excessive vaginal
      bleeding after an uncertain amenorrheal period. The patient presented with
      preshock vital signs, severe anemia, and a positive urine pregnancy test. Imaging
      examinations revealed a massive intrauterine mass (19 * 15 * 10 cm), suggesting a
      complete hydatidiform mole. She was hospitalized and treated with blood
      transfusion. Sixteen hours after hospitalization, the massive molar mass
      underwent spontaneous expulsion and bleeding ceased. Three days after the
      expulsion, she developed pruritic skin lesions including papules, erythemas, and
      bullae, which spread over her entire body. Skin biopsy revealed PG and
      subepidermal blister formation and linear complement C3 deposition along the
      basement membrane zone, and the serum anti-BP180 antibody level was found to be
      high on measurement. She was effectively treated with 50 mg/day of oral
      prednisolone. Her skin lesions disappeared, leaving pigmentation. 

PMID- 24083042
TI  - Polydactyly 24 in a female neonate.
AB  - Polydactyly is perhaps one of the most common congenital hand and foot anomalies.
      Tetrapolydactyly (polydactyly 24) is a very rare form of hand and foot anomalies.
      Postaxial ray polydactyly usually occurs in male blacks without associated
      congenital abnormalities. We report a case of postaxial ray tetrapolydactyly in a
      female neonate which occurred sporadically and without associated congenital
      abnormalities. 

PMID- 24083043
TI  - Parachordoma of soft tissues of the arm: a very rare tumour.
AB  - Parachordoma is an infrequent neoplasm that bears some histologic resemblance to
      chordoma. It affects both sexes, occurs typically during the fourth decade of
      life, and tends to present as a slow-growing painless mass at the level of the
      soft tissues of the extremities. Diagnosis should be based on immunohistochemical
      and cytogenetic studies, as the findings of imaging techniques are often
      unspecific. Although it is considered a benign lesion, its behavior tends to be
      locally aggressive, with reports of a recurrence rate of up to 20% and of several
      cases of metastasis. Fewer than 60 cases have been published in the English
      speaking literature. In this paper we present the case of a 32-year-old male with
      a two-year history of parachordoma in the right wrist. 

PMID- 24083044
TI  - A rare case of congenital simple cystic ranula in a neonate.
AB  - Congenital ranula in a neonate is an uncommon occurrence. We present one such
      case of the said lesion where the clinical presentation and management were found
      to be interesting, hitherto unreported in the medical literature. This clinical
      record also reviews the scant medical literature on congenital ranula in
      neonates. 

PMID- 24083045
TI  - Pleural Fluid Cytology of the Polymorphous Variant of EBV-Positive Diffuse Large
      B-Cell Lymphoma: First Report and Distinction from a Reactive Process.
AB  - EBV-positive diffuse large B-cell lymphoma of the elderly is a newly described
      aggressive lymphoma predominantly affecting patients >50 years of age. Patients
      may present with nodal and/or extranodal involvement. The lung is one of the more
      common extranodal sites. The incidence of pleural fluid involvement is less well
      described. In one study by Oyama et al., pleural effusions were noted in nine
      percent of cases. Identification of pleural fluid involvement could be important
      as it may carry prognostic importance in staging (it typically occurs more often
      in cases with widespread disease), and it could be a relatively easy means of
      establishing a diagnosis in newly presenting cases. We report the first
      description of the pleural fluid cytology in a case of EBV-positive diffuse large
      B-cell lymphoma of the elderly. 

PMID- 24083046
TI  - Adult nephroblastoma with predominant epithelial component: a differential
      diagnostic candidate of papillary renal cell carcinoma and metanephric adenoma
      report of three cases.
AB  - Although nephroblastoma is the commonest renal tumor of childhood, it is rare in
      adults. In cases of predominantly epithelial type occurring in adulthood, it
      might be difficult to distinguish it from papillary renal cell carcinoma and
      metanephric adenoma. Here, we report three cases of adult epithelial
      nephroblastoma in 24-, 76-, and 21-year-old females. Histologically, the tumors
      were composed of papillotubular architectures of small and uniform tumor cells
      with high nucleocytoplasmic ratio without blastemal element.
      Immunohistochemically, the tumor cells were positive for WT-1 and CD57 but
      negative for AMACR, which was helpful to exclude the possibility of papillary
      renal cell carcinoma. Metanephric adenoma is a benign tumor, which can be
      distinguished by the observation of the cellular atypism and growth pattern.
      However, nephroblastoma with predominant epithelial element mimics the malignant
      counterpart of metanephric adenoma, that is, "metanephric adenocarcinoma." 

PMID- 24083047
TI  - Snake envenomation causing distant tracheal myonecrosis.
AB  - Snakebites are often believed to be poisonous. However, this is not always the
      case. In fact, each bite differs from snake to snake, depending on if the snake
      is poisonous and if there is envenomation. Venom in pit viper snakebites is often
      associated with local necrosis. The abundant literature selections and research
      articles justify local myonecrosis due to envenomation, but there is not much in
      the literature regarding myonecrosis at a site distant from the snakebite. We
      hereby present a case of a 42-year-old man who was transferred to our emergency
      department after a rattlesnake bit him twice. The patient, besides developing
      local myonecrosis at the site of the snakebite, developed necrosis of the scrotum
      as well as tracheal pressure myonecrosis at the site of the endotracheal tube
      balloon. In this review, we will attempt to discuss the myonecrosis
      pathophysiology and management related to the rattle snakebite. 

PMID- 24083048
TI  - Medicolegal considerations with intravenous tissue plasminogen activator in
      stroke: a systematic review.
AB  - Background. Intravenous tPA (tissue plasminogen activator) therapy remains
      underutilized in patients with Acute Ischemic Stroke (AIS). Anecdotal data
      indicates that physicians are increasingly liable for administering and for
      failure to administer tPA. Methods. An extensive search of Medline, Embase,
      Westlaw, LexisNexis Legal, and Google Scholar databases was performed. Case
      studies that involved malpractice litigation in ischemic stroke and thrombolytic
      therapy were analyzed systematically. Results. We identified 789 ischemic stroke
      litigation cases, of which 46 cases were related to intravenous tPA and stroke
      litigation. Case descriptions of 40 cases were available. Data for verdicts were
      available for 38 patients. The most frequent plaintiff claim was related to
      failure to administer intravenous tPA (38, 95%). Only 2 (5.0%) claim involved
      complications of treatment with tPA. Hospitals were defendants in majority of the
      36 cases. Physicians were involved in 33 cases. While ED physicians were involved
      in 25 (60.52%) cases, neurologists were involved in 8 (20.0%) cases. There were
      26 (65%) defendant-favored and 12 (30%) plaintiff-favored verdicts. Conclusion.
      Physicians and hospitals are at an increased risk of litigation in patients with
      AIS when in IV-tPA is being considered for treatment. While majority of the cases
      litigated were cases where tPA was not administered, only about 1 in 20 cases was
      litigated when complications occurred. 

PMID- 24083049
TI  - Comparison of thermal coagulation profiles for bipolar forceps with different
      cooling mechanisms in a porcine model of spinal surgery.
AB  - BACKGROUND: Coagulation accomplished using bipolar forceps is common in
      neurosurgery. Control of thermal spread from the forceps tips into surrounding
      neural tissues is a persistent concern, as neural tissues are especially
      vulnerable to heat injury. The purpose of our investigation was to compare the
      efficacy of cooling mechanisms for four different bipolar forceps and to
      understand thermal spread when coagulating vessels on the spinal cord. METHODS:
      Immediately following euthanasia, the dura mater of an ex vivo porcine model was
      opened to expose vessels on the spinal cord for coagulation. Temperature profiles
      were measured at generator power of 25 W and at fixed 5-second activation times.
      The bipolar forceps used in this study included regular stainless steel,
      titanium, heat-pipe embedded, and SILVERGlide forceps. Temperature was measured
      by micro-thermistor at the midpoint between the bipolar tips, and 1 and 2 mm away
      from the midpoint along the centerline. Statistical analysis was performed to
      evaluate temperature differences. RESULTS: Temperature profiles indicated that
      heat-pipe embedded forceps create the least amount of temperature increase and
      the highest normalized temperature decreasing slope after activation. The
      decreasing slope of SILVERGlide forceps is slightly higher than that of regular
      stainless steel forceps. CONCLUSIONS: Bipolar forceps incorporating either heat
      pipe embedded technology or SILVERGlide coating can effectively limit excessive
      thermal spread, thus decreasing potential injury to adjacent tissues when
      compared with standard stainless steel and titanium bipolar forceps. Of the two,
      heat-pipe embedded technology appeared safest, having better cooling efficiency
      at higher temperature.

PMID- 24083050
TI  - Immediate and follow-up results for 44 consecutive cases of small (<10 mm)
      internal carotid artery aneurysms treated with the pipeline embolization device.
AB  - BACKGROUND: The pipeline embolization device (PED) provides effective, durable
      and safe endovascular reconstruction of large and giant intracranial aneurysms.
      However, 80% of all cerebral aneurysms found in the general population are less
      than 10 mm in size. Treatment of small aneurysms (<10 mm) with flow diverters may
      be advantageous over endosaccular modalities that carry risks of procedural
      rupture during aneurysm access or coil placement. METHODS: We retrospectively
      reviewed a prospective, single-center aneurysm database to identify all patients
      with small (<10 mm) internal carotid artery (ICA) aneurysms who underwent
      endovascular treatment using the PED. Patient demographics, aneurysm
      characteristics, procedural details, complications, and technical and clinical
      outcomes were analyzed. RESULTS: Forty-four cases were performed in 41 patients
      (age range 31-78 years). PED was successfully implanted in 42 cases. A single PED
      was used in 37/42 (88%) cases. Mean postprocedure hospital stay was 1.7 +/- 0.3
      days and 98% of patients were discharged home. Major complication occurred in one
      patient (2.3%), who died of early subarachnoid hemorrhage. Transient neurological
      deficit, delayed intracerebral hemorrhage (asymptomatic), and delayed groin
      infection occurred in one patient each. Follow-up rate was 91.8% (45 aneurysms in
      35 patients) with a mean follow-up of 4.0 +/- 1.9 months. By 6 months post-PED
      implantation, angiographic success (complete or near complete aneurysm occlusion)
      was observed in 80%. Mild (<50%), asymptomatic, nonflow limiting in-stent
      stenosis was observed in 5.4% (2/37 cases). All the 35 patients with follow-up
      remained at preprocedure neurological baseline. CONCLUSION: Small (<10 mm) ICA
      aneurysm treatment with PED implantation is safe and carries a high rate of early
      angiographic success.

PMID- 24083051
TI  - Four-fold benefit of wound closure under high magnification.
AB  - BACKGROUND: Unaffected wound healing and good cosmetic result after a
      neurosurgical procedure are important factors measuring a level of care. The
      usefulness of high magnification of the operating microscope during closure of
      neurosurgical wounds is evaluated. METHODS: During a one-year microneurosurgical
      fellowship, the first author (JK) performed wound closure under the microscope in
      200 of 524 neurosurgical operations carried out by the senior author (JH) at the
      Department of Neurosurgery, Helsinki University Central Hospital. Supratentorial
      approaches were employed most frequently in 143 patients (72%). Surgeries for
      infratentorial lesions and the spinal canal comprised 48 (24%) and 9 procedures
      (4%), respectively. Mean duration of the surgery from skin to skin was 1.8 (range
      0.5-6.2) hours. After intradural hemostasis was completed by the senior author,
      further steps including dural suturing, bone flap fixation, and wound closure
      were performed by the first author. Wound condition was assessed during the early
      and late postoperative period. Mean follow-up was 3.2 (range 1-10) months.
      RESULTS: Early postoperative healing of the wound was uneventful in 180 patients
      (90%). No wound rupture or postoperative hematoma occurred. In five patients
      (2.5%), lumbar puncture or spinal drainage was necessary due to significant
      subcutaneous liquor collection. No wound revision was required. At follow-up, in
      196 patients (98%) the postoperative scar was in perfect condition. Neither skin
      necrosis nor healing problems occurred. CONCLUSION: Based on our results, we
      found the high magnification of operating microscope to be beneficial when
      closing neurosurgical wounds; it allows (1) better hemostasis, (2) precise wound
      margin approximation, (3) atraumatic handling of the tissues, and (4) improvement
      of the manual dexterity of the neurosurgeon.

PMID- 24083052
TI  - Trigeminocardiac reflex in neurosurgical practice: An observational prospective
      study.
AB  - BACKGROUND: Considering wide variations regarding the incidence of
      trigeminocardiac reflex (TCR) during cranial neurosurgical procedures, and
      paucity of reliable data, we intended to design a prospective study to determine
      the incidence of TCR in patients undergoing standard general anesthesia for
      surgery of supra/infra-tentorial cranial and skull base lesions. METHODS: A total
      of 190 consecutive patients candidate for elective surgery of supra-tentorial,
      infra-tentorial, and skull base lesions were enrolled. All the patients were
      operated in the neurosurgical operating room of a university-affiliated teaching
      hospital. All surgeries were performed using sufficient depth of anesthesia
      achieved by titration of propofol-alfentanil mixture, adjusted according to
      target Cerebral State Index (CSI) values (40-60). All episodes of bradycardia and
      hypotension indicating the occurrence of TCR during the surgery (sudden decrease
      of more than 20% from the previous level) were recorded. RESULTS: Four patients,
      two female and two male, developed episodes of TCR during surgery (4/190; 2.1%).
      Three patients showed one episode of TCR just at the end of operation when the
      skin sutures were applied while CSI values were 70-77 and in the last case, when
      small tumor samples were taken from just beneath the lateral wall of the
      cavernous sinus TCR episode was seen while the CSI value was 51. CONCLUSION: TCR
      is a rare phenomenon during brain surgeries when patient is anesthetized using
      standard techniques. Keeping the adequate depth of anesthesia using CSI
      monitoring method may be an advisable strategy during whole period of a
      neurosurgical procedure.

PMID- 24083054
TI  - Ossification of the ligamentum flavum as cause of thoracic cord compression: Case
      report of a Latin American man and review of the literature.
AB  - BACKGROUND: Ossification of the ligamentum flavum is a widely described pathology
      in eastern Asia. Cases have been reported in northern Africa, the Middle-East,
      India, the Caribbean, Europe, and North America, but no cases from Latin America
      have been published in the literature. It affects mostly elderly men, with a
      possible association with obesity and type 2 diabetes. CASE DESCRIPTION: A 38
      year-old previously healthy Latin American male presented to the emergency room
      department with severe functional disability and a 3/5 paraparesis. Blood reports
      showed no abnormalities. Computed tomography and magnetic resonance imaging
      showed a ligamentum flavum ossification with myelopathy. The patient underwent a
      T3-T9 laminotomy. At hospital discharge, the patient remained with a 3/5
      paraparesis, mild hypoesthesia in both lower limbs and bladder incontinence.
      Rectal sphincter was continent. At 6 months, he was able to walk with a cane,
      with no sphincter or sensory alterations. CONCLUSIONS: Ligamentum flavum
      ossification is rare. To our understanding, this is the first case reported in
      the Latin American population.

PMID- 24083055
TI  - Neuronavigation-guided endoscopic and hodotopic approach to an arachnoid cyst.
AB  - BACKGROUND: Arachnoid cysts are intraarachnoid benign cystic lesions filled with
      cerebrospinal fluid and should be treated without incurring further morbidity to
      the patients. CASE DESCRIPTION: The authors present a case of a 68-year-old
      elderly female with a large right fronto-parieto-temporal arachnoid cyst who has
      been suffering from mild left hemiparesis for the past 4 years and presented with
      sudden onset of seizures. The 3 Tesla MR system with diffusion tensor imaging
      (DTI) and MR tractography of the brain showed a large right fronto-parieto
      temporal cystic lesion measuring 7 * 5 * 5 cm with a midline shift of 1 cm,
      suggestive of an arachnoid cyst with surrounding ipsilateral white matter
      projection pathways and inferior occipito-frontal fasciculus or inferior
      longitudinal white matter tracts. The cyst was successfully treated with
      neuronavigation-guided endoscopic and hodotopical approach to fenestrate the
      arachnoid cyst into the sylvian cistern, avoiding inadvertent injury to major
      white matter tracts portrayed by DTI. Postoperatively, a repeated computed
      tomography (CT) scan of the brain revealed a smaller arachnoid cyst with
      correction of the midline shift. The patient was weaned off from the ventilator
      and her hemiplegia improved gradually. CONCLUSION: This case report emphasizes
      the value of neuronavigation-guided endoscopic and hodotopic approach to
      fenestrate the intra-axial arachnoid cyst.

PMID- 24083053
TI  - Immunology primer for neurosurgeons and neurologists part 2: Innate brain
      immunity.
AB  - Over the past several decades we have learned a great deal about microglia and
      innate brain immunity. While microglia are the principle innate immune cells,
      other cell types also play a role, including invading macrophages, astrocytes,
      neurons, and endothelial cells. The fastest reacting cell is the microglia and
      despite its name, resting microglia (also called ramified microglia) are in fact
      quite active. Motion photomicrographs demonstrate a constant movement of ramified
      microglial foot processes, which appear to be testing the microenvironment for
      dangerous alteration in extracellular fluid content. These foot processes, in
      particular, interact with synapses and play a role in synaptic function. In event
      of excitatory overactivity, these foot processes can strip selected synapses,
      thus reducing activation states as a neuroprotective mechanism. They can also
      clear extracellular glutamate so as to reduce the risk of excitotoxicity.
      Microglia also appear to have a number of activation phenotypes, such as: (1)
      phagocytic, (2) neuroprotective and growth promoting, or (3) primarily
      neurodestructive. These innate immune cells can migrate a great distance under
      pathological conditions and appear to have anatomic specificity, meaning they can
      accumulate in specifically selected areas of the brain. There is some evidence
      that there are several types of microglia. Macrophage infiltration into the
      embryonic brain is the source of resident microglia and in adulthood macrophages
      can infiltrate the brain and are for the most part pathologically
      indistinguishable from resident microglia, but may react differently. Activation
      itself does not imply a destructive phenotype and can be mostly neuroprotective
      via phagocytosis of debris, neuron parts and dying cells and by the release of
      neurotrophins such as nerve growth factor (NGF) and brain derived neurotrophic
      factor (BDNF). Evidence is accumulating that microglia undergo dynamic
      fluctuations in phenotype as the neuropathology evolves. For example, in the
      early stages of neurotrauma and stroke, microglia play a mostly neuroprotective
      role and only later switch to a neurodestructive mode. A great number of
      biological systems alter microglia function, including neurohormones,
      cannabinoids, other neurotransmitters, adenosine triphosphate (ATP), adenosine,
      and corticosteroids. One can appreciate that with aging many of these systems are
      altered by the aging process itself or by disease thus changing the sensitivity
      of the innate immune system. 

PMID- 24083056
TI  - Relationship between magnification and resolution in digital pathology systems.
AB  - Many pathology laboratories are implementing digital pathology systems. The image
      resolution and scanning (digitization) magnification can vary greatly between
      these digital pathology systems. In addition, when digital images are compared
      with viewing images using a microscope, the cellular features can vary in size.
      This article highlights differences in magnification and resolution between the
      conventional microscopes and the digital pathology systems. As more pathologists
      adopt digital pathology, it is important that they understand these differences
      and how they ultimately translate into what the pathologist can see and how this
      may impact their overall viewing experience. 

PMID- 24083057
TI  - Eliminating tissue-fold artifacts in histopathological whole-slide images for
      improved image-based prediction of cancer grade.
AB  - BACKGROUND: Analysis of tissue biopsy whole-slide images (WSIs) depends on
      effective detection and elimination of image artifacts. We present a novel method
      to detect tissue-fold artifacts in histopathological WSIs. We also study the
      effect of tissue folds on image features and prediction models. MATERIALS AND
      METHODS: We use WSIs of samples from two cancer endpoints - kidney clear cell
      carcinoma (KiCa) and ovarian serous adenocarcinoma (OvCa) - publicly available
      from The Cancer Genome Atlas. We detect tissue folds in low-resolution WSIs using
      color properties and two adaptive connectivity-based thresholds. We optimize and
      validate our tissue-fold detection method using 105 manually annotated WSIs from
      both cancer endpoints. In addition to detecting tissue folds, we extract 461
      image features from the high-resolution WSIs for all samples. We use the rank-sum
      test to find image features that are statistically different among features
      extracted from the same set of WSIs with and without folds. We then use features
      that are affected by tissue folds to develop models for predicting cancer grades.
      RESULTS: When compared to the ground truth, our method detects tissue folds in
      KiCa with 0.50 adjusted Rand index (ARI), 0.77 average true rate (ATR), 0.55 true
      positive rate (TPR), and 0.98 true negative rate (TNR); and in OvCa with 0.40
      ARI, 0.73 ATR, 0.47 TPR, and 0.98 TNR. Compared to two other methods, our method
      is more accurate in terms of ARI and ATR. We found that 53 and 30 image features
      were significantly affected by the presence of tissue-fold artifacts (detected
      using our method) in OvCa and KiCa, respectively. After eliminating tissue folds,
      the performance of cancer-grade prediction models improved by 5% and 1% in OvCa
      and KiCa, respectively. CONCLUSION: The proposed connectivity-based method is
      more effective in detecting tissue folds compared to other methods. Reducing
      tissue-fold artifacts will increase the performance of cancer-grade prediction
      models.

PMID- 24083058
TI  - Extracting laboratory test information from biomedical text.
AB  - BACKGROUND: No previous study reported the efficacy of current natural language
      processing (NLP) methods for extracting laboratory test information from
      narrative documents. This study investigates the pathology informatics question
      of how accurately such information can be extracted from text with the current
      tools and techniques, especially machine learning and symbolic NLP methods. The
      study data came from a text corpus maintained by the U.S. Food and Drug
      Administration, containing a rich set of information on laboratory tests and test
      devices. METHODS: THE AUTHORS DEVELOPED A SYMBOLIC INFORMATION EXTRACTION (SIE)
      SYSTEM TO EXTRACT DEVICE AND TEST SPECIFIC INFORMATION ABOUT FOUR TYPES OF
      LABORATORY TEST ENTITIES: Specimens, analytes, units of measures and detection
      limits. They compared the performance of SIE and three prominent machine learning
      based NLP systems, LingPipe, GATE and BANNER, each implementing a distinct
      supervised machine learning method, hidden Markov models, support vector machines
      and conditional random fields, respectively. RESULTS: Machine learning systems
      recognized laboratory test entities with moderately high recall, but low
      precision rates. Their recall rates were relatively higher when the number of
      distinct entity values (e.g., the spectrum of specimens) was very limited or when
      lexical morphology of the entity was distinctive (as in units of measures), yet
      SIE outperformed them with statistically significant margins on extracting
      specimen, analyte and detection limit information in both precision and F
      measure. Its high recall performance was statistically significant on analyte
      information extraction. CONCLUSIONS: Despite its shortcomings against machine
      learning methods, a well-tailored symbolic system may better discern relevancy
      among a pile of information of the same type and may outperform a machine
      learning system by tapping into lexically non-local contextual information such
      as the document structure.

PMID- 24083059
TI  - Hypothermic Perfusion Preservation of Pancreas for Islet Grafts: Validation Using
      a Split Lobe Porcine Model.
AB  - The demand for high-quality islets for transplantation in type I diabetics will
      increase as the current clinical trials transition into standard of care. The
      mode of preservation of donor pancreata is critical to this mission since islets
      are very sensitive to ischemic injury. Hypothermic perfusion preservation (HPP)
      is being investigated for extended pancreas preservation in light of the
      beneficial effects reported for other organs. The present pilot study aimed to
      establish the potency of porcine islets isolated from pancreata after 24 h of HPP
      at 4-8 degrees C. The study design included a split-lobe pancreas model that
      permitted paired comparisons of islets isolated from 24-h HPP splenic lobes with
      nonperfused, fresh control duodenal/connecting lobes stored at 4 degrees C for <3
      h. Prior to transplantation, islet viability was assessed in vitro using the
      ratio of oxygen consumption rate to DNA (OCR/DNA) assay and correlated with
      subsequent in vivo function by transplantation in diabetic immunodeficient mice.
      The OCR/DNA (mean +/- SD) measured after 7 days of culture and immediately prior
      to transplantation for islets from the 24-h HPP group was 269 +/- 19 nmol/min/mg
      DNA, which was higher but not statistically different to the mean of 236 +/- 43
      for the counterpart control group. All four nude mice transplanted with islets
      from the 24-h HPP group showed diabetes reversal, compared with five of six
      transplants from the control group. In conclusion, islets isolated from adult
      porcine pancreata after 24-h HPP exhibited high viability as measured by OCR/DNA
      and were able to consistently reverse diabetes in a nude mouse bioassay.

PMID- 24083060
TI  - Antiretroviral Therapy (ART) Side Effect Impacted on Quality of Life, and
      Depressive Symptomatology: A Mixed-Method Study.
AB  - Antiretroviral therapy (ART) is known for its side effects. In this paper, we
      describe ART side effects as experienced by Chinese HIV+ individuals. This study
      presents two stages of a research project, combining qualitative in-depth
      interviews (29 HIV+ participants) with quantitative statistical data analysis (N
      = 120). All data was collected between July 2005 to March 2008 at Beijing's Ditan
      Hospital. Consent was obtained from each participant for the qualitative
      interview and again for the quantitative survey. During in-depth interviews,
      Chinese HIV+ patients reported experiencing digestive discomfort, skin rashes,
      numbness, memory loss, nightmares, and dizziness, which not only brought them
      physical discomfort, but also interrupted different dimensions of their social
      lives. Furthermore, multiple regression analyses revealed that those who reported
      more severe side effects also experienced greater depressive mood after
      controlling for other clinical and psychosocial factors. ART side effects are one
      of the primary reasons causing HIV+ individuals to delay or stop taking life
      saving medication; therefore, clinical interventions are critically needed to
      assist HIV+ individuals in managing ART side effects. ART side effects reinforced
      existing negative attitudes toward ART and lead to lower ART adherence. Future
      research should focus on developing culturally sensitive interventions to enhance
      HIV+ self-management, to alleviate physical and psychological burden from ART and
      HIV.

PMID- 24083061
TI  - Camptodactyly-arthropathy-coxa vara-pericarditis syndrome: important differential
      for juvenile idiopathic arthritis.
AB  - Camptodactyly-arthropathy-coxa vara-pericarditis (CACP) syndrome is an inherited
      disorder characterized by congenital or early-onset flexion camptodactyly,
      childhood-onset of non-inflammatory arthropathy, often associated with non
      inflammatory pericarditis or pericardial effusion and progressive coxa vara. The
      causative gene is located on chromosome band 1q25-31. This gene encodes for
      "proteoglycan-4" (PRG-4), which is a surface lubricant for joints and tendons.
      This syndrome has distinct radiological and histological features, which are
      important to recognize since it may clinically mimic juvenile idiopathic
      arthritis and mutation studies may not be easily available. We describe a case of
      a 3-year 3-month-old female with features of CACP syndrome. 

PMID- 24083062
TI  - Spontaneous biliary peritonitis in children.
AB  - Pediatric Spontaneous Bile duct perforation is a rare clinical condition with
      only around 150 cases reported worldwide. Early management gives excellent
      prognosis but the condition often presents a diagnostic dilemma. Hepato-biliary
      Technetium-99m-iminodiacetic acid scintiscan is the diagnostic investigation of
      choice but its availability in third world countries is limited. We present two
      cases of spontaneous biliary peritonitis in children, which were diagnosed
      without scintiscanning. The first case was a one-and -a half-year-old child, who
      was diagnosed with biliary peritonitis without pneumoperitoneum by a combination
      of Ultrasound (USG), Contrast enhanced computed tomography (CECT), and Magnetic
      Resonance Imaging (MRI). The child underwent USG-guided drainage and subsequent
      cholecystectomy with hepatico-jejunostomy. The second child also had biliary
      peritonitis without pneumoperitoneum, which was initially suspected on USG. CECT
      revealed dilated gall bladder and fluid collection in sub-hepatic space and
      pelvis. Abdominal paracentesis revealed presence of bile. The child responded to
      conservative therapy. Both are doing well on two-year follow-up. In a patient
      with jaundice, biliary tract abnormalities and/or free fluid, either generalized
      or localized to peri-cholecystic/sub-hepatic space on USG/CT/MRI, in the absence
      of pneumoperitoneum, suggest a diagnosis of biliary perforation even in the
      absence of scintiscanning. 

PMID- 24083063
TI  - Clinico-radiologic Findings in Group II Caudal Regression Syndrome.
AB  - Caudal regression syndrome (CRS) is a rare congenital abnormality in which a
      segment of the lumbo-sacral spine and spinal cord fails to develop. The severity
      of the morphologic derangement inversely correlates with residual spinal cord
      function. We present a case report of a 10-year-old girl with Group 2 CRS, to
      emphasize clinical and radiologic findings in this rare abnormality. 

PMID- 24083064
TI  - Association of progesterone, pessary, and antibiotic for treating pregnant woman
      with short cervix syndrome: importance of magnetic resonance imaging in the
      assessment of pessary position.
AB  - Preterm delivery (PD) is the most important cause of neonatal mortality,
      particularly before the 32(nd) week of pregnancy. A short cervix is the most
      important quantitative marker for predicting PD. However, there are other
      qualitative markers such as cervical gland area, cervical funneling, and sludge.
      We present the case of a pregnant woman who was diagnosed with a short cervix at
      14-weeks and demonstrate the use of triple therapy, which helped to achieve a
      good perinatal result. A 37-year-old pregnant woman (G3P0) was referred to our
      service at 14-weeks of pregnancy presenting with a short cervix (20 mm) and a
      positive sludge sign. She was hospitalized; a pessary was inserted, and started
      on antibiotic therapy (clindamycin and cefalotin for 10 days). At 20 weeks, she
      was again admitted to the hospital, and this time presented with a further
      shortened cervix (9 mm), cervical funneling, and a positive sludge sign, with the
      pessary in position. The following procedures were performed: Amniocentesis on
      the sludge (negative bacterioscopy), another cycle of antibiotics, administration
      of oral progesterone, and imaging to determine retention of pessary position. The
      patient was placed in the Trendelenburg position and remained hospitalized for 82
      days. At 32 + 1 weeks, the fetus presented distress (tachycardia). C-section was
      performed, producing a live female newborn weighing 2,180 g and presenting Apgar
      indexes of 8/8. This case report demonstrates the importance of magnetic
      resonance imaging to assess the position of pessary in a pregnant woman with
      short cervix. 

PMID- 24083065
TI  - Correlation of ultrasonographic parameters with serum creatinine in chronic
      kidney disease.
AB  - OBJECTIVE: The purpose of our study is to correlate renal echogenicity with serum
      creatinine in order to determine the significance of renal echogenicity when it
      comes to identifying the progression of chronic kidney disease (CKD) and for the
      sonographic grading of CKD. MATERIALS AND METHODS: Sixty patients above 30 years
      of age who had been diagnosed with CKD according to the guidelines of the
      National Kidney Foundation were included in the study. Patients on kidney
      replacement therapy or with fatty liver findings on ultrasonography were
      excluded. Ultrasounds of kidneys were performed by two radiologists who were
      blind to the patients' serum creatinine levels. Renal cortical echogenicity was
      compared with serum creatinine. Statistical analysis was performed using one-way
      ANOVA followed by Scheffe's test. The relationship between serum creatinine and
      sonographic features was assessed by correlation coefficient analysis. A P value
      less than 0.05 was considered statistically significant. RESULTS: Mean serum
      creatinine was 2.80 mg/dl for Grade 1 (range: 0.9-9.2 mg/dl), 3.69 mg/dl for
      Grade 2 (range: 1.2-10.3 mg/dl), 3.86 mg/dl for Grade 3 (range: 1.1-6.5 mg/dl),
      and 7.90 mg/dl for Grade 4 (range: 3.1-11.4 mg/dl). The grades being determined
      by cortical echogenicity on imaging A statistically significant, positive
      correlation was observed between serum creatinine and grading based on cortical
      echogenicity (P = 0.004). CONCLUSION: Renal echogenicity and its grading
      correlates better with serum creatinine in CKD than other sonographic parameters
      such as longitudinal size, parenchymal thickness, and cortical thickness. Hence,
      renal echogenicity is a better parameter than serum creatinine for estimating
      renal function in CKD, and has the added advantage of irreversibility.

PMID- 24083066
TI  - Transjugular intrahepatic portosystemic shunt for maintenance of portal venous
      patency in liver transplant candidates.
AB  - Maintenance of portal venous patency is vital to liver transplant candidates, as
      the presence of portal vein thrombosis (PVT) adversely impacts clinical outcomes
      by increasing surgical complexity and decreasing postoperative survival. By
      enhancing portal venous blood flow, transjugular intrahepatic portosystemic shunt
      (TIPS) creation may enable clearance of PVT and preservation of portal venous
      patency in cirrhotic patients. Herein, we describe four cases in which TIPS
      produced and sustained an open portal venous system in liver transplant
      candidates with partial PVT. All patients demonstrated rapid and effective flow
      enabled clearance of clot and intermediate to long-term preservation of portal
      venous flow. On this basis, we propose that maintenance of portal venous patency
      in liver transplant candidates with partial PVT represents a developing
      indication for TIPS. 

PMID- 24083067
TI  - A rare cause of crazy-paving and mediastinal lymphadenopathy: congestive heart
      failure.
AB  - Crazy-paving sign is a pattern seen on multislice computed tomography images of
      the lungs. It is characterized by a reticular pattern superimposed on ground
      glass opacity. It was first described in the late 1980s in patients with
      pulmonary alveolar proteinosis, but has now been described in some other diseases
      of the lung. Enlarged mediastinal lymph nodes can be seen in infectious and
      specific inflammatory diseases and malignancies. The present report describes a
      case of a 44-year-old man in whom congestive heart failure presented with a crazy
      paving appearance and enlarged lymph nodes of the lungs on the chest computed
      tomography scan. 

PMID- 24083068
TI  - A rare cause of acute abdomen: jejunal diverticulosis with perforation.
AB  - Jejunal diverticulosis is generally asymptomatic and is associated with high
      morbidity and mortality secondary to complications, especially in elderly
      patients. We present a case report of a 74-year-old female patient with jejunal
      diverticulosis and perforation due to diverticulitis. 

PMID- 24083069
TI  - Functioning Adrenocortical Carcinoma with Extension upto the Right Atrium
      Producing Cushing's Syndrome.
AB  - Adrenocortical carcinoma (ACC) is a rare malignancy with poor prognosis. Surgery
      is the only curative therapy available and overall 5-year survival for patients
      who undergo a complete resection is 32% to 48%. They are known to produce
      intravascular invasion and into the inferior vena cava (IVC) and in rare cases
      they may reach the right atrium. We report a case of functioning ACC extending
      into the inferior vena cava and right atrium in a female with Cushing's syndrome.

PMID- 24083070
TI  - Localized cystic disease of the kidney: a rare cause of hypertension in a young
      adult.
AB  - Localized cystic disease of kidney (LCDK) is a rare, non-familial, non
      progressive renal disorder that is not associated with cysts or disorders in
      other organs. Only a few cases have been reported in the literature. While this
      condition is morphologically identical to the autosomal dominant form of
      polycystic kidney disease, it is not inherited and is not associated with
      significant deterioration of renal function. We present a case of a 16-year-old
      male patient who suffered from hypertension for over two years. On imaging we
      found several, variable-sized cysts in the upper half of the right kidney. The
      left kidney and lower segment of the right kidney were normal. Selective renal
      vein catheterization and sampling showed markedly elevated renin level in the
      right upper segmental vein (92 pg/ml, normal value: 11-33 pg/ml). The patient
      underwent a right upper heminephrectomy and histopathology was suggestive of
      LCDK. After surgery, the patient's blood pressure returned to normal levels
      without any need of antihypertensive medication and he is under follow-up on
      outpatient basis for the past two years. 

PMID- 24083071
TI  - Magnetic resonance imaging of benign cardiac masses: a pictorial essay.
AB  - The differential diagnosis for a cardiac mass includes primary and metastatic
      neoplasms. While primary cardiac tumors are rare, metastatic disease to the heart
      is a common finding in cancer patients. Several "tumor-like" processes can mimic
      a true cardiac neoplasm with accurate diagnosis critical at guiding appropriate
      management. We present a pictorial essay of the most common benign cardiac masses
      and "mass-like" lesions with an emphasis on magnetic resonance imaging features. 

PMID- 24083072
TI  - Semantic Dementia Diagnosed by F-18 FDG PET/MRI: Co-registered Images.
AB  - We report a case of a 61-year-old male who presented with a sudden change in
      mental status. From a psychiatric standpoint, his symptoms were consistent with a
      bipolar disorder. A neurology consult raised suspicion for vascular dementia,
      given the sudden onset of symptoms; however, the magnetic resonance angiography
      (MRA) was unremarkable. The magnetic resonance imaging (MRI) had findings that
      were suggestive of both vascular and frontotemporal lobe dementia based on
      parenchymal atrophy and a lacunar infarct near the thalamus. However, by co
      registering the magnetic resonance images with a subsequent fluorine-18
      Fluorodeoxyglucose positron emission tomography (F-18 FDG PET), and combining the
      functional data with the anatomic appearance, the diagnosis was narrowed to
      semantic dementia, which is one of the lesser known subtypes of frontotemporal
      lobe dementia (FTD). 

PMID- 24083073
TI  - Laminin Functionalized Biomimetic Nanofibers For Nerve Tissue Engineering.
AB  - Large-gap peripheral nerve injuries present a significant challenge for nerve
      regeneration due to lack of suitable grafts, insufficient cell penetration, and
      repair. Biomimetic nanofibrous scaffolds, functionalized on the surface with
      extracellular matrix proteins, can lead to novel therapies for repair and
      regeneration of damaged peripheral nerves. Here, nanofibrous scaffolds
      electrospun from blends of poly(caprolactone) (PCL) and chitosan were fabricated.
      Taking advantage of the amine groups on the chitosan, the surface of the
      scaffolds were functionalized with laminin by carbodiimide based crosslinking.
      Crosslinking allowed laminin to be attached to the surfaces of the PCL-chitosan
      nanofibers at relatively high concentrations that were not possible using
      conventional adsorption methods. The nanofibrous meshes were tested for
      wettability, mechanical properties and cell attachment and proliferation.
      Blending of chitosan with PCL provided more favorable surfaces for attachment of
      Schwann cells due to the reduction of the contact angle in comparison to neat
      PCL. Proliferation rates of Schwann cells grown on PCL-chitosan scaffolds with
      crosslinked laminin were significantly higher than the rates for PCL-chitosan
      nanofibrous matrices with adsorbed laminin. PCL-chitosan scaffolds with modified
      surfaces via crosslinking of laminin could potentially serves as versatile
      substrates with excellent mechanical and surface properties for in vivo cell
      delivery for nerve tissue engineering applications.

PMID- 24083074
TI  - Function-first antibody discovery: Embracing the unpredictable biology of
      antibodies.
AB  - Therapeutic antibodies may mediate antineoplastic effects by altering the
      biological functions of their target, by directly stimulating the demise of
      cancer cells or by activating antibody-dependent immune effector mechanisms. We
      have recently provided in vivo proof-of-concept for a "function-first" target and
      drug discovery platform in which antibodies against a multitude of tumor
      associated antigens are screened for biological effects in a target-unbiased
      manner.

PMID- 24083075
TI  - Myeloid-derived suppressor cells as a Trojan horse: A cellular vehicle for the
      delivery of oncolytic viruses.
AB  - We have recently demonstrated that oncolytic vesicular stomatitis viruses can be
      efficiently and selectively delivered to neoplastic lesions by myeloid-derived
      suppressor cells (MDSCs). Importantly, the loading of viruses onto MDSCs
      inhibited their immunosuppressive properties and endowed them with
      immunostimulatory and tumoricidal functions. Our study demonstrates the potential
      use of MDSCs as a Trojan horse for the tumor-targeted delivery of various
      anticancer therapeutics.

PMID- 24083076
TI  - Combination of a Toll-like receptor 9 agonist with everolimus interferes with the
      growth and angiogenic activity of renal cell carcinoma.
AB  - The mTOR inhibitor everolimus is currently approved for the treatment of renal
      cell carcinoma (RCC) and several Toll-like receptor 9 (TLR9) agonists, including
      immunomodulatory oligonucleotides (IMOs), have been tested for their therapeutic
      potential against advanced RCC. However, no clinical trials investigating the
      combination of mTOR inhibitors with TLR9 agonists in RCC patients have been
      performed to date. Our results may pave the way to translate this combinatorial
      approach to the clinical setting.

PMID- 24083077
TI  - MicroRNAs as novel immunotherapeutics.
AB  - A large unmet need exists for cost-effective, widely available antineoplastic
      immunotherapeutic agents with a robust translational potential. MicroRNAs
      (miRNAs) that regulate tumor-mediated immunosuppression or immune checkpoints can
      induce robust therapeutic immune responses, indicating that miRNAs may ultimately
      become part of the portfolio of anticancer immunotherapeutics.

PMID- 24083078
TI  - VEGFA/VEGFR2-targeted therapies prevent the VEGFA-induced proliferation of
      regulatory T cells in cancer.
AB  - Some of the anti-angiogenic agents currently used to treat solid malignancies
      have effects on tumor endothelial cells as well as on immune cells. We have
      recently demonstrated that targeting the vascular endothelial growth factor A
      (VEGFA)/VEGF receptor 2 (VEGFR2) signaling pathway reduces the proportion of
      regulatory T cells (Treg) in a mouse model of colorectal cancer (CRC) and in
      metastatic CRC patients as it inhibits tumor-induced Treg proliferation.

PMID- 24083079
TI  - How the devil facial tumor disease escapes host immune responses.
AB  - The devil facial tumor disease (DFTD) is a contagious cancer that has recently
      emerged among Tasmanian devils, rapidly decimating the population. We have
      recently discovered that DFTD cells lose the expression MHC molecules on the cell
      surface, explaining how this tumor avoids recognition by host CD8+ T cells.

PMID- 24083081
TI  - Could the properties of IL-27 make it an ideal adjuvant for anticancer
      immunotherapy?
AB  - We have recently been the first to demonstrate that interleukin (IL)-27 protects
      against the emergence and progression of autochthonous tumors. Accumulating
      evidence suggests that IL-27 might be uniquely well positioned to amplify
      beneficial TH1 anticancer immune responses while suppressing the unwanted
      accumulation of regulatory T cells.

PMID- 24083082
TI  - Interferon gamma-induced intratumoral expression of CXCL9 alters the local
      distribution of T cells following immunotherapy with Listeria monocytogenes.
AB  - The ability of Listeria monocytogenes-based anticancer vaccines to induce tumor
      regression depends on the responsiveness of malignant cells to interferon gamma
      (IFNgamma). Inhibition of IFNgamma limits the recruitment of T cells to the
      tumors of vaccinated mice. We hypothesized that vaccination with
      immunotherapeutic L. monocytogenes induces the IFNgamma-dependent production of
      chemokines that regulate the migration of tumor-infiltrating T cells. To gain
      further insights into this issue, we examined the chemokine responses of a
      transplantable, human papillomavirus (HPV)-immortalized murine tumor model (TC-1)
      following the administration of a L. monocytogenes-based immunotherapeutic agent
      that expresses E7 from HPV-16. Here, we report that the administration of L.
      monocytogenes-based anticancer vaccines increases the secretion of chemokine (C-X
      C motif) ligand 9 (CXCL9), and CXCL10 by tumors, hence favoring the recruitment
      of T cells bearing the cognate chemokine (C-X-C motif) receptor 3 (CXCR3).
      Furthermore, the expression of CXCL9, but not CXCL10, in TC-1 tumors was
      significantly reduced upon anti-IFNgamma antibody treatment. CXCL9 was highly
      expressed by TC-1 cells following the administration of IFNgamma and tumor
      necrosis factor alpha (TNFalpha), in vitro. Moreover, the inhibition of CXCL9 in
      TC-1 cells reduced the proportion of CD8+ T cells infiltrating tumors in
      vaccinated mice, while increasing that of CD4+ T cells, thus altering T-cell
      subset distribution. We conclude that the administration of L. monocytogenes
      based anticancer vaccines regulates TH1 chemokine responses and that malignant
      cells are an important source of these chemokines.

PMID- 24083083
TI  - Blocking the B7-H4 pathway with novel recombinant antibodies enhances T cell
      mediated antitumor responses.
AB  - B7-H4 inhibits T-cell activation and is widely expressed by solid neoplasms. We
      have recently demonstrated that the expression of B7-H4 on the surface of
      malignant cells in vivo is inducible, and that novel anti-B7-H4 recombinant
      antibodies can reverse the inhibition of tumor-specific T cells. Thus, antibodies
      targeting the B7-H4 pathways may extend the survival of cancer patients by
      restoring T cell-mediated antitumor responses.

PMID- 24083080
TI  - Trial Watch: Toll-like receptor agonists for cancer therapy.
AB  - Toll-like receptors (TLRs) have long been known for their ability to initiate
      innate immune responses upon exposure to conserved microbial components such as
      lipopolysaccharide (LPS) and double-stranded RNA. More recently, this family of
      pattern recognition receptors has been attributed a critical role in the
      elicitation of anticancer immune responses, raising interest in the development
      of immunochemotherapeutic regimens based on natural or synthetic TLR agonists. In
      spite of such an intense wave of preclinical and clinical investigation, only
      three TLR agonists are currently licensed by FDA for use in cancer patients:
      bacillus Calmette-Guerin (BCG), an attenuated strain of Mycobacterium bovis that
      operates as a mixed TLR2/TLR4 agonist; monophosphoryl lipid A (MPL), a derivative
      of Salmonella minnesota that functions as a potent agonist of TLR4; and
      imiquimod, a synthetic imidazoquinoline that activates TLR7. One year ago, in the
      August and September issues of OncoImmunology, we described the main biological
      features of TLRs and discussed the progress of clinical studies evaluating the
      safety and therapeutic potential of TLR agonists in cancer patients. Here, we
      summarize the latest developments in this exciting area of research, focusing on
      preclinical studies that have been published during the last 13 mo and clinical
      trials launched in the same period to investigate the antineoplastic activity of
      TLR agonists.

PMID- 24083084
TI  - Immune modulation of the tumor microenvironment for enhancing cancer
      immunotherapy.
AB  - There is much promise in the use of immunotherapy for the treatment of cancer.
      Approaches such as those using antibodies or adoptive cell transfer can mediate
      complete tumor regression in a proportion of patients. However, the tumor
      microenvironment can inhibit immune responses leading to ineffective or
      suboptimal responses of tumors to immunotherapy in the majority of cases. As our
      knowledge of the tumor microenvironment increases, many strategies are emerging
      for changing the immunosuppressive nature of the tumor toward a microenvironment
      able to support immunity. These strategies aim to enhance the ability of
      immunotherapies to initiate effective immune responses able to destroy tumors. In
      this article, we review approaches that use immunomodulators specifically to
      modify the tumor microenvironment, and their use in combination with other immune
      based strategies for cancer therapy.

PMID- 24083085
TI  - Immunological monitoring of anticancer vaccines in clinical trials.
AB  - Therapeutic anticancer vaccines operate by eliciting or enhancing an immune
      response that specifically targets tumor-associated antigens. Although intense
      efforts have been made for developing clinically useful anticancer vaccines, only
      a few Phase III clinical trials testing this immunotherapeutic strategy have
      achieved their primary endpoint. Here, we report the results of a retrospective
      research aimed at clarifying the design of previously completed Phase II/III
      clinical trials testing therapeutic anticancer vaccines and at assessing the
      value of immunological monitoring in this setting. We identified 17 anticancer
      vaccines that have been investigated in the context of a completed Phase II/III
      clinical trial. The immune response of patients receiving anticancer vaccination
      was assessed for only 8 of these products (in 15 distinct studies) in the attempt
      to identify a correlation with clinical outcome. Of these studies, 13 were
      supported by a statistical correlation study (Log-rank test), and no less than 12
      identified a positive correlation between vaccine-elicited immune responses and
      disease outcome. Six trials also performed a Cox proportional hazards analysis,
      invariably demonstrating that vaccine-elicited immune responses have a positive
      prognostic value. However, despite these positive results in the course of early
      clinical development, most therapeutic vaccines tested so far failed to provide
      any clinical benefit to cancer patients in Phase II/III studies. Our research
      indicates that evaluating the immunological profile of patients at enrollment
      might constitute a key approach often neglected in these studies. Such an
      immunological monitoring should be based not only on peripheral blood samples but
      also on bioptic specimens, whenever possible. The evaluation of the immunological
      profile of cancer patients enrolled in early clinical trials will allow for the
      identification of individuals who have the highest chances to benefit from
      anticancer vaccination, thus favoring the rational design of Phase II and Phase
      III studies. This approach will undoubtedly accelerate the clinical development
      of therapeutic anticancer vaccines.

PMID- 24083087
TI  - Detecting the Progression of Eye Disease: CUSUM Charts for Assessing the Visual
      Field and Retinal Nerve Fiber Layer Thickness.
AB  - PURPOSE: The cumulative sum (CUSUM) is proposed and tested in a group of glaucoma
      patients and healthy subjects as a method for monitoring disease progression and
      for identifying clinically significant step changes in visual structure or
      function. METHODS: The CUSUM procedure is the recommended method for the timely
      detection of small step changes in manufacturing process control. The CUSUM
      procedure is discussed and compared with traditional approaches for the detection
      of change in the status of the visual system over time. The CUSUM approach is
      used to monitor over time visual field (VF) mean deviations and optical coherence
      tomography (OCT) measurements of retinal nerve fiber layer (RNFL) thickness in 53
      healthy subjects and 103 patients with glaucoma. RESULTS: The CUSUM method
      detects VF progression for 35 of the 103 glaucoma patients (34.0%), and OCT RNFL
      reductions for 20 of the 103 glaucoma patients (19.4%). CONCLUSIONS: The CUSUM
      method is effective in detecting small level changes. This method can be used to
      monitor the progression of disease and it benefits the clinician who must decide,
      on the basis of a time series of variable data, whether a change has occurred.
      TRANSLATIONAL RELEVANCE: A cumulative sum chart helps the clinician decide
      whether a step change has taken place, and it does so as quickly as possible.
      This approach is particularly effective for detecting small step changes, which
      very likely are unnoticed with currently used change detection approaches.

PMID- 24083086
TI  - Oncolytic vesicular stomatitis virus quantitatively and qualitatively improves
      primary CD8+ T-cell responses to anticancer vaccines.
AB  - The ability of heterologous prime-boost vaccination to elicit robust CD8+ T cell
      responses has been well documented. In contrast, relatively little is known about
      how this immunotherapeutic strategy impacts the functional qualities of expanded
      T cells in the course of effector and memory responses. Using vesicular
      stomatitis virus (VSV) as a boosting vector in mice, we demonstrate that a
      massive secondary expansion of CD8+ T cells can be achieved shortly after priming
      with recombinant adenoviral vectors. Importantly, VSV-boosted CD8+ T cells were
      more potent than those primed by adenoviruses only, as measured by cytokine
      production, granzyme B expression, and functional avidity. Upon adoptive
      transfer, equivalent numbers of VSV-expanded CD8+ T cells were more effective (on
      a per-cell basis) in mediating antitumor and antiviral immunity than T cells only
      primed with adenoviruses. Furthermore, VSV boosting accelerated the progression
      of expanded CD8+ T lymphocytes to a central memory phenotype, thereby altering
      the effector memory profile typically associated with adenoviral vaccination.
      Finally, the functional superiority of VSV-expanded T cells remained evident 100
      d after boosting, suggesting that VSV-driven immunological responses are of
      sufficient duration for therapeutic applications. Our data strongly support the
      choice of VSV as a boosting vector in prime-boost vaccination strategies,
      enabling a rapid amplification of CD8+ T cells and improving the quality of
      expanded T cells during both early and late immunological responses.

PMID- 24083088
TI  - Development of a surgically optimized graft insertion suture technique to
      accommodate a tissue-engineered tendon in vivo.
AB  - The traumatic rupture of tendons is a common clinical problem. Tendon repair is
      surgically challenging because the tendon often retracts, resulting in a gap
      between the torn end and its bony insertion. Tendon grafts are currently used to
      fill this deficit but are associated with potential complications relating to
      donor site morbidity and graft necrosis. We have developed a highly reproducible,
      rapid process technique to manufacture compressed cell-seeded type I collagen
      constructs to replace tendon grafts. However, the material properties of the
      engineered constructs are currently unsuitable to withstand complete load bearing
      in vivo. A modified suture technique has been developed to withstand
      physiological loading and off load the artificial construct while integration
      occurs. Lapine tendons were used ex vivo to test the strength of different suture
      techniques with different sizes of Prolene sutures and tissue-engineered collagen
      constructs in situ. The data were compared to standard modified Kessler suture
      using a standard tendon graft. Mechanical testing was carried out and a finite
      element analysis stress distribution model constructed using COMSOL 3.5 software.
      The break point for modified suture technique with a tissue-engineered scaffold
      was significantly higher (50.62 N) compared to a standard modified Kessler suture
      (12.49 N, p<0.05). Distributing suture tension further proximally and distally
      from the tendon ends increased the mechanical strength of the repairs. We now
      have ex vivo proof of concept that this suture technique is suitable for testing
      in vivo, and this will be the next stage of our research. 

PMID- 24083089
TI  - Production of a recombinant antibody specific for i blood group antigen, a
      mesenchymal stem cell marker.
AB  - Multipotent mesenchymal stem/stromal cells (MSCs) offer great promise for future
      regenerative and anti-inflammatory therapies. Panels of functional and
      phenotypical markers are currently used in characterization of different
      therapeutic stem cell populations from various sources. The i antigen (linear
      poly-N-acetyllactosamine) from the Ii blood group system has been suggested as a
      marker for MSCs derived from umbilical cord blood (UCB). However, there are
      currently no commercially available antibodies recognizing the i antigen. In the
      present study, we describe the use of antibody phage display technology to
      produce recombinant antibodies recognizing a structure from the surface of
      mesenchymal stem cells. We constructed IgM phage display libraries from the
      lymphocytes of a donor with an elevated serum anti-i titer. Antibody phage
      display technology is not dependent on immunization and thus allows the
      generation of antibodies against poorly immunogenic molecules, such as
      carbohydrates. Agglutination assays utilizing i antigen-positive red blood cells
      (RBCs) from UCB revealed six promising single-chain variable fragment (scFv)
      antibodies, three of which recognized epitopes from the surface of UCB-MSCs in
      flow cytometric assays. The amino acid sequence of the VH gene segment of B12.2
      scFv was highly similar to the VH4.21 gene segment required to encode anti-i
      specificities. Further characterization of binding properties revealed that the
      binding of B12.2 hyperphage was inhibited by soluble linear lactosamine
      oligosaccharide. Based on these findings, we suggest that the B12.2 scFv we have
      generated is a prominent anti-i antibody that recognizes i antigen on the surface
      of both UCB-MSCs and RBCs. This binder can thus be utilized in UCB-MSC detection
      and isolation as well as in blood group serology. 

PMID- 24083091
TI  - Substantial differences between human and ovine mesenchymal stem cells in
      response to osteogenic media: how to explain and how to manage?
AB  - It is expected that use of adult multipotential mesenchymal stem cells (MSCs) for
      bone tissue engineering (TE) will lead to improvement of TE products. Prior to
      clinical application, biocompatibility of bone TE products need to be tested in
      vitro and in vivo. In orthopedic research, sheep are a well-accepted model due to
      similarities with humans and are assumed to be predictive of human outcomes. In
      this study we uncover differences between human and ovine bone marrow-derived
      MSCs (BMSCs) and adipose tissue-derived MSCs (ADSCs) in response to osteogenic
      media. Osteogenic differentiation of BMSCs and ADSCs was monitored by alkaline
      phosphatase (ALP) activity and calcium deposition. Mineralization of ovine BMSC
      was achieved in medium containing NaH2PO4 as a source of phosphate ions (Pi), but
      not in medium containing beta-glycerophosphate (beta-GP), which is most often
      used. In a detailed study we found no induction of ALP activity in ovine BMSCs
      and ADSCs upon osteogenic stimulation, which makes beta-GP an unsuitable source
      of phosphate ions for ovine cells. Moreover, mineralization of human ADSCs was
      more efficient in osteogenic medium containing NaH2PO4. These results indicate
      major differences between ovine and human MSCs and suggest that standard in vitro
      osteogenic differentiation techniques may not be suitable for all types of cells
      used in cell-based therapies. Since mineralization is a widely accepted marker of
      the osteogenic differentiation and maturation of cells in culture, it may lead to
      potentially misleading results and should be taken into account at the stage of
      planning and interpreting preclinical observations performed in animal models. We
      also present a cell culture protocol for ovine ADSCs, which do not express ALP
      activity and do not mineralize under routine pro-osteogenic conditions in vitro.
      We plan to apply it in preclinical experiments of bone tissue-engineered products
      performed in an ovine model. 

PMID- 24083090
TI  - Human placental alkaline phosphatase as a tracking marker for bone marrow
      mesenchymal stem cells.
AB  - Currently, adult mesenchymal stem cells (MSCs) are being evaluated for a wide
      variety of therapeutic approaches. It has been suggested that MSCs possess
      regenerative properties when implanted or injected into damaged tissue. However,
      the efficacy of MSCs in several of the proposed treatments is still
      controversial. To further explore the therapeutic potential of these cells, it is
      necessary to trace the fate of individual donor or manipulated cells in the host
      organism. Recent studies from our lab showed that human placental alkaline
      phosphatase (hPLAP) is a marker with great potential for cell tracking. However,
      a potential concern related to this marker is its enzymatic activity, which might
      alter cell behavior and differentiation by hydrolyzing substrates in the
      extracellular space and thereby changing the cellular microenvironment.
      Therefore, the aim of this study was to characterize bone marrow MSCs (BMSCs)
      derived from hPLAP-transgenic inbred F344 rats (hPLAP-tg) in comparison to wild
      type (wt) BMSCs. Here, we show that BMSCs from wt and hPLAP-tg donors are
      indistinguishable in terms of cell morphology, viability, adhesion, immune
      phenotype, and proliferation as well as in their differentiation capacity over
      six passages. The expression of the hPLAP marker enzyme was not impaired by
      extensive in vitro cultivation, osteogenic, adipogenic, or chondrogenic
      differentiation, or seeding onto two- or three-dimensional biomaterials. Thus,
      our study underscores the utility of genetically labeled BMSCs isolated from
      hPLAP-tg donors for long-term tracking of the fate of transplanted MSCs in
      regenerative therapies. 

PMID- 24083093
TI  - Biofabrication under fluorocarbon: a novel freeform fabrication technique to
      generate high aspect ratio tissue-engineered constructs.
AB  - Bioprinting is a recent development in tissue engineering, which applies rapid
      prototyping techniques to generate complex living tissues. Typically, cell
      containing hydrogels are dispensed layer-by-layer according to a computer
      generated three-dimensional model. The lack of mechanical stability of printed
      hydrogels hinders the fabrication of high aspect ratio constructs. Here we
      present submerged bioprinting, a novel technique for freeform fabrication of
      hydrogels in liquid fluorocarbon. The high buoyant density of fluorocarbons
      supports soft hydrogels by floating. Hydrogel constructs of up to 30-mm height
      were generated. Using 3% (w/v) agarose as the hydrogel and disposable syringe
      needles as nozzles, the printer produced features down to 570-MUm diameter with a
      lateral dispensing accuracy of 89 MUm. We printed thin-walled hydrogel cylinders
      measuring 4.8 mm in height, with an inner diameter of ~2.9 mm and a minimal wall
      thickness of ~650 MUm. The technique was successfully applied in printing a model
      of an arterial bifurcation. We extruded under fluorocarbon, cellularized alginate
      tubes with 5-mm outer diameter and 3-cm length. Cells grew vigorously and formed
      clonal colonies within the 7-day culture period. Submerged bioprinting thus seems
      particularly suited to fabricate hollow structures with a high aspect ratio like
      vascular grafts for cardiovascular tissue engineering as well as branching or
      cantilever-like structures, obviating the need for a solid support beneath the
      overhanging protrusions. 

PMID- 24083092
TI  - Role of material-driven fibronectin fibrillogenesis in protein remodeling.
AB  - Protein remodeling at the cell-material interface is an important phenomenon that
      should be incorporated into the design of advanced biomaterials for tissue
      engineering. In this work, we address the relationship between fibronectin (FN)
      activity at the material interface and remodeling, including proteolytic
      cascades. To do so, we studied FN adsorption on two chemically similar
      substrates, poly(ethyl acrylate) (PEA) and poly(methyl acrylate) (PMA), which
      resulted in different distribution and conformation of the protein at the
      material interface: FN organized spontaneously upon adsorption on PEA into
      physiological-like fibrils, through a process called material-driven FN
      fibrillogenesis. The amount of adsorbed FN and its conformation were investigated
      in two different coating concentrations (2 and 20 MUg/mL). Since FN activity at
      the material interface determines the initial cellular response, we followed the
      formation of focal adhesions (vinculin) and subsequent cell signaling by focal
      adhesion kinase (FAK) expression and its phosphorylation (pFAK). More detailed
      studies were performed to get further insights into integrin binding by
      crosslinking and extraction followed by immunofluorescence, as well as protein
      and gene expression for alpha5 and alphav. To correlate cell adhesion with matrix
      degradation, gene expression and activity (zymography) of matrix
      metalloproteinases (MMPs) were measured. Overall, we demonstrated that the
      material-driven FN fibrillogenesis triggers proteolytic activity: MMP activity
      was higher on the material-driven FN fibrils, as a compensatory mechanism to the
      inability of cells to reorganize this FN network. 

PMID- 24083094
TI  - Effects of Succinic Acid and Other Microbial Fermentation Products on HIV
      Expression in Macrophages.
AB  - Bacterial vaginosis (BV), a common condition in women, is associated with
      increased shedding of HIV in the female genital tract. While the Lactobacillus
      species that comprise a healthy vaginal microbiota produce lactic acid, the
      bacteria common in BV produce high concentrations of short chain fatty acids
      (SCFAs) and succinic acid. Macrophages are abundant in the lower genital tract
      mucosa and are thought to play an important role in HIV infection. In this study,
      we investigated whether SCFAs and succinic acid impacted HIV expression in
      monocyte-derived macrophages. Monocytes differentiated with either granulocyte
      macrophage colony-stimulating factor (GM-CSF) or macrophage colony-stimulating
      factor (M-CSF) were infected with either HIVBal or an HIV-luciferase reporter
      virus and treated with SCFAs, succinic acid, or lactic acid. Butyric acid
      suppressed HIV expression while succinic acid significantly increased expression
      in macrophages differentiated with either GM-CSF or M-CSF. Acetic, propionic, and
      lactic acids had no effect on HIV expression. Only succinic acid resulted in a
      significant increase in interleukin-8 production by infected macrophages. Our
      results suggest that succinic acid present in increased concentrations in the
      genital tract of women with BV plays a pro-inflammatory role and increases HIV
      expression. This could be one factor contributing to increased virus shedding
      seen in women with BV. 

PMID- 24083097
TI  - Zygmunt Bauman. Individual and society in the liquid modernity.
AB  - Starting from the postmodern, the philosophical and sociological speculation by
      Zygmunt Bauman, opens - through the analysis of the phenomenon of globalization -
      to the meta-level of life, and then circumscribes the most recent thinking on
      political life, until reaching the liquid modernity: overcoming postmodernity
      itself. As a result individual, society, ethics, power, religion become those
      words impregnated with a liquidity capable of condensing in itself the most
      significant aspects of the present reality: a dimension in which the lasting
      gives way to the transient, the need to the desire, and the necessity to the
      utility. 

PMID- 24083095
TI  - Global consensus sequence development and analysis of dengue NS3 conserved
      domains.
AB  - The dengue virus (DENV) genome encodes 10 different genes including the NS3 gene,
      which has a protease and helicase domain used in virus replication. This domain
      is a potential target for antiviral agents against dengue. Due to a high mutation
      rate, DENV is classified into four major serotypes (DENV1-DENV4). This study was
      designed to perform conservancy analysis of all four serotypes by drawing a
      consensus sequence for each serotype and then drawing a global consensus sequence
      to study conserved residues in all four serotypes. A total of 127 NS3 sequences
      belonging to all four serotypes were retrieved and aligned using multiple
      alignment feature of CLC Workbench and were subjected to phylogenetic tree
      construction. Conservancy analysis of NS3 revealed conserved peptides with active
      site residues that can be important in developing antiviral agents against dengue
      virus. Among conserved residues, residues G142, Ser144, and G145 (catalytic
      pocket residues), A219, D220, and D221 (divalent cations binding residues), and
      His56, Asp79, Ser144, 146 were highly conserved among all the serotypes. Residues
      from L138 to L149 and from L226 to L245 were also considerably conserved in all
      serotypes, while lysine141 mutated to serine in serotype 3. A total of 14
      peptides from the conserved regions of DENV NS3 protein were identified, which
      may be helpful to develop peptide inhibitors. The DENV NS3 phylogenetic tree
      showed the evolutionary relationship among all four serotypes, and all serotypes
      of dengue were found to have evolved from the dengue 4 serotype. Because of its
      high variability, DENV has become a global health concern. It is important to
      study residues that are present in protease, helicase, the catalytic pocket
      Mg(2+) binding site, and the AAA domain. This study revealed peptides with active
      site residues that are highly conserved among all four serotypes. These regions
      of the NS3 sequence may be helpful in developing antiviral agents. 

PMID- 24083098
TI  - Prediction of sea water intrusion for mining activity in close precincts of sea
      shore.
AB  - The mining lease area of Surka [District Bhavnagar, Gujarat (India)] is located
      within 6-12 km horizontal distance of sea shore of Gulf of Cambay. Whenever,
      there will be onset of lignite extraction, there will be always a threat of sea
      water intrusion into the mining lease area due to its close proximity to
      seashore. This article describes the prediction of sea water intrusion into the
      lease area of whole mining block using Ghyben-Herzberg relation between fresh and
      saline water, Remote Sensing, Ground Truth verification, Electrical Resistivity
      Survey and groundwater table monitored during the year 2004. As per the Ghyben
      Herzberg relation, results show that there will not be sea water intrusion. If
      there is excess pumping of water then also the basement rock below the lignite
      seam will put hindrance to any possible upconing of saline water interface. 

PMID- 24083099
TI  - Synthesis and optimization ring opening of monoepoxide linoleic acid using p
      toluenesulfonic acid.
AB  - Biolubricant base oils, 9,12-hydroxy-10,13-oleioxy-12-octadecanoic acid (HYOOA)
      was synthesized based on the esterification reaction of Monoepoxide linoleic acid
      9(12)-10(13)-monoepoxy 12(9)-octadecanoic acid (MEOA) with oleic acid (OA) and
      catalyzed by p-Toluenesulfonic acid. The optimum conditions for the experiment
      using D-optimal design to obtain high yield% of 84.61, conversion% of 83.54 and
      lowest OOC% of 0.05 were predicted at OA/MEOA ratio of 0.2:1 (mol/mol), PTSA/MEOA
      ratio of 0.4:1 (mol/mol), reaction temperature at 110 degrees C, and reaction
      time at 4.5 h. The FTIR peaks of HYOOA indicate the disappearance of the
      absorption band at 820 cm(-1), which belongs to the oxirane ring. (13)C and (1)H
      NMR spectra analyses confirmed the result of HYOOA with appearance carbon-ester
      (C = O) chemical shift at 174.1 ppm and at 4.06 ppm for (13)C and (1)H NMR
      respectively. 

PMID- 24083100
TI  - Contribution of extrahepatic small cells resembling small hepatocyte-like
      progenitor cells to liver mass maintenance in transplantation model of retrorsine
      pretreated liver.
AB  - PURPOSE: Retrorsine selectively inhibits hepatocyte proliferation and following
      liver injury evokes small hepatocyte-like progenitor cells. The aim of this study
      is to find out whether endogenous extrahepatic cells contribute to small
      hepatocyte-like progenitor cells after retrorsine treatment. METHODS: Wild-type
      Lewis rat liver exposed to retrorsine was transplanted into GFP transgenic Lewis
      rat. GFP positive, albumin-producing polygonal cells were expected as reciepient
      derived hepatocyte-like cells. RESULTS: Four weeks after transplantation of 50%
      volume of retrorsine-pretreated liver, the rate of GFP positive hepatocyte-like
      cells was 0.02365%. Majority of these cells resided as single cells and their
      cell size was significantly larger than that of normal hepatocytes (mean cell
      size; 799.4 um(2) vs. 451.3 um(2), p<0.0001). At eight weeks, clusters of GFP
      positive small-size albumin-producing cells appeared and occupied 0.00759% of
      hepatocytes. The morphology of these cells was similar to that of small
      hepatocyte-like progenitor cells, 12.5% of them were Ki67 positive, majority of
      them were negative for CYP1A2 staining, and some clusters contained larger cells
      indicating further maturation. CONCLUSION: Endogenous extrahepatic cells can form
      a cluster of small cells resembling small hepatocyte-like progenitor cells in a
      transplanted retrorsine-pretreated liver. The contribution of extrahepatic cells
      to liver mass maintenance is quite low and its importance is unclear.

PMID- 24083101
TI  - Analysis of functional xylanases in xylan degradation by Aspergillus niger E-1
      and characterization of the GH family 10 xylanase XynVII.
AB  - Xylanases produced by Aspergillus niger are industrially important and many types
      of xylanases have been reported. Individual xylanases have been well studied for
      their enzymatic properties, gene cloning, and heterologous expression. However,
      less attention has been paid to the relationship between xylanase genes carried
      on the A. niger genome and xylanases produced by A. niger strains. Therefore, we
      examined xylanase genes encoded on the genome of A. niger E-1 and xylanases
      produced in culture. Seven putative xylanase genes, xynI-VII (named in ascending
      order of the molecular masses of the deduced amino acid sequences), were
      amplified from the strain E-1 genome using primers designed from the genome
      sequence of A. niger CBS 513.88 by PCR and phylogenetically classified into three
      clusters. Additionally, culture supernatant analysis by DE52 anion-exchange
      column chromatography revealed that this strain produced three xylanases, XynII,
      XynIII, and XynVII, which were identified by N-terminal amino acid sequencing and
      MALDI-TOF-MS analyses, in culture when gown in 0.5% xylan medium supplemented
      with 50 mM succinate. Furthermore, XynVII, the only GH family 10 xylanase in A.
      niger E-1, was purified and characterized. The purified enzyme showed a single
      band with a molecular mass of 35 kDa by SDS-PAGE. The highest activity of
      purified XynVII was observed at 55 degrees C and pH 5.5. The enzyme was stable in
      the broad pH range of 3-10 and up to 60 degrees C and was resistant to most metal
      ions and modifying regents. XynVII showed high specificity against beechwood
      xylan with K m and V max values of 2.8 mg mL(-1) and 127 MUmol min(-1)mg(-1),
      respectively. TLC and MALDI-TOF-MS analyses showed that the final hydrolyzed
      products of the enzyme from beechwood xylan were xylose, xylobiose, and
      xylotriose substituted with a 4-o-metylglucuronic acid residue. 

PMID- 24083102
TI  - Associations between null mutations in GSTT1 and GSTM1, the GSTP1 Ile(105)Val
      polymorphism, and mortality in breast cancer survivors.
AB  - PURPOSE: Here we assessed associations between null mutations in glutathione-S
      transferase (GST)T1 and GSTM1 genes, and the rs1695 polymorphism in GSTP1
      (Ile(105)Val), and risk of breast cancer-specific (n=45) and all-cause (n=99)
      mortality in a multiethnic, prospective cohort of 533 women diagnosed with stage
      I-IIIA breast cancer in 1995-1999, enrolled in the Health, Eating, Activity, and
      Lifestyle (HEAL) Study. METHODS: We measured the presence of the null mutation in
      GSTT1 and GSTM1, and the rs1695 polymorphism in GSTP1 by polymerase chain
      reaction. We assessed associations between breast-cancer specific and all-cause
      mortality using Cox proportional hazards models. RESULTS: Participants with ER
      negative tumors were more likely to be GSTT1 null (chi(2)=4.52; P=0.03), and
      African American women were more likely to be GSTM1 null (chi(2)=34.36;
      P<0.0001). Neither GSTM1 nor GSTT1 null mutations were associated with breast
      cancer-specific or all-cause mortality. In a model adjusted for body mass index,
      race/ethnicity, tumor stage and treatment received at diagnosis, the variant Val
      allele of rs1695 was associated with increased risk of all-cause (HR=1.81, 95% CI
      1.16-2.82, P=0.008), but not breast cancer-specific mortality. The GSTT1 null
      mutation was associated with significantly higher levels of C-reactive protein.
      CONCLUSIONS: GSTM1 and GSTT1 null genotypes had no effect on outcome; however the
      variant allele of rs1695 appears to confer increased risk for all-cause mortality
      in breast-cancer survivors. Given the limited sample size of most studies
      examining associations between GST polymorphisms with breast cancer survival, and
      the lack of women undergoing more contemporary treatment protocols (treated prior
      to 1999), it may be helpful to re-examine this issue among larger samples of
      women diagnosed after the late 1990s, who all received some form of chemotherapy
      or radiotherapy.

PMID- 24083103
TI  - Ontology in association rules.
AB  - Data mining has emerged to address the problem of transforming data into useful
      knowledge. Although most data mining techniques, such as the use of association
      rules, may substantially reduce the search effort over large data sets, often,
      the consequential outcomes surpass the amount of information humanly manageable.
      On the other hand, important association rules may be overlooked owing to the
      setting of the support threshold, which is a very subjective metric, but rooted
      in most data mining techniques. This paper presents a study on the effects, in
      terms of precision and recall, of using a data preparation technique, called
      SemPrune, which is built on domain ontology. SemPrune is intended for pre- and
      post-processing phases of data mining. Identifying generalization/specialization
      relations, as well as composition/decomposition relations, is the key to
      successfully applying SemPrune. 

PMID- 24083104
TI  - Quantifying uncertainty in measurement of mercury in suspended particulate matter
      by cold vapor technique using atomic absorption spectrometry with hydride
      generator.
AB  - As a result of rapid industrialization several chemical forms of organic and
      inorganic mercury are constantly introduced to the environment and affect humans
      and animals directly. All forms of mercury have toxic effects; therefore accurate
      measurement of mercury is of prime importance especially in suspended particulate
      matter (SPM) collected through high volume sampler (HVS). In the quantification
      of mercury in SPM samples several steps are involved from sampling to final
      result. The quality, reliability and confidence level of the analyzed data
      depends upon the measurement uncertainty of the whole process. Evaluation of
      measurement uncertainty of results is one of the requirements of the standard
      ISO/IEC 17025:2005 (European Standard EN IS/ISO/IEC 17025:2005, issue1:1-28,
      2006). In the presented study the uncertainty estimation in mercury determination
      in suspended particulate matter (SPM) has been carried out using cold vapor
      Atomic Absorption Spectrometer-Hydride Generator (AAS-HG) technique followed by
      wet chemical digestion process. For the calculation of uncertainty, we have
      considered many general potential sources of uncertainty. After the analysis of
      data of seven diverse sites of Delhi, it has been concluded that the mercury
      concentration varies from 1.59 +/- 0.37 to 14.5 +/- 2.9 ng/m(3) with 95%
      confidence level (k = 2). 

PMID- 24083105
TI  - Percutaneous transluminal renal angioplasty with stenting for stenotic venous
      bypass grafts: report of two cases.
AB  - Cases of percutaneous transluminal renal angioplasty for renal artery stenosis
      are increasing. However, percutaneous transluminal renal angioplasty with
      stenting for stenotic venous bypass grafts has never been reported. Herein, the
      authors describe two cases of percutaneous transluminal renal angioplasty with
      stenting for a stenotic venous bypass graft. The patients in both cases had
      undergone bypass grafting using autologous saphenous veins, which were
      anastomosed directly to their abdominal aortas. We successfully conducted
      percutaneous transluminal renal angioplasty with stenting. One of the keys for
      technical success is an appropriate selection of guiding catheter compatible with
      postoperative nonanatomical vasculature, and the other is relatively high
      pressure dilation for venous stenosis. 

PMID- 24083106
TI  - Discovery of novel plastid phenylalanine (trnF) pseudogenes defines a distinctive
      clade in Solanaceae.
AB  - BACKGROUND: The plastome of embryophytes is known for its high degree of
      conservation in size, structure, gene content and linear order of genes. The
      duplication of entire tRNA genes or their arrangement in a tandem array composed
      by multiple pseudogene copies is extremely rare in the plastome. Pseudogene
      repeats of the trnF gene have rarely been described from the chloroplast genome
      of angiosperms. FINDINGS: We report the discovery of duplicated copies of the
      original phenylalanine (trnFGAA) gene in Solanaceae that are specific to a larger
      clade within the Solanoideae subfamily. The pseudogene copies are composed of
      several highly structured motifs that are partial residues or entire parts of the
      anticodon, T- and D-domains of the original trnF gene. CONCLUSIONS: The
      Pseudosolanoid clade consists of 29 genera and includes many economically
      important plants such as potato, tomato, eggplant and pepper.

PMID- 24083107
TI  - Immunohistochemical study of pituitary cells in wild and captive Salminus hilarii
      (Characiformes: Characidae) females during the annual reproductive cycle.
AB  - Freshwater fish that live exclusively in rivers are at particular risk from
      fragmentation of the aquatic system, mainly the species that migrate upriver for
      reproduction. That is the case of Salminus hilarii, an important migratory
      species currently classified as "almost threatened" in the Sao Paulo State
      (Brazil), facing water pollution, dam construction, riparian habitat destruction
      and environmental changes that are even more serious in this State. Additionally,
      this species show ovulation dysfunction in captivity. Our studies focused on the
      identification and distribution of the pituitary cell types in the
      adenohypophysis of S. hilarii females, including a morphometric analysis that
      compares pituitary cells from wild and captive broodstocks during the
      reproductive annual cycle. The morphology of adenohypophysial cells showed
      differences following the reproductive cycle and the environment. In general,
      optical density suggested a higher cellular activity during the previtellogenic
      (growth hormone) and vitellogenic (somatolactin) stages in both environments.
      Additionally, the nucleus/cell ratio analysis suggested that growth hormone and
      somatolactin cells were larger in wild than in captive females in most
      reproductive stages of the annual cycle. In contrast, prolactin hormone showed no
      variation throughout the reproductive cycle (in both environments).
      Morphometrical analyses related to reproduction of S. hilarii in different
      environmental conditions, suggest that somatolactin and growth hormone play an
      important role in reproduction in teleost and can be responsible for the
      regulation of associated processes that indirectly affect reproductive status. 

PMID- 24083108
TI  - Optimal multiobjective design of digital filters using spiral optimization
      technique.
AB  - The multiobjective design of digital filters using spiral optimization technique
      is considered in this paper. This new optimization tool is a metaheuristic
      technique inspired by the dynamics of spirals. It is characterized by its
      robustness, immunity to local optima trapping, relative fast convergence and ease
      of implementation. The objectives of filter design include matching some desired
      frequency response while having minimum linear phase; hence, reducing the time
      response. The results demonstrate that the proposed problem solving approach
      blended with the use of the spiral optimization technique produced filters which
      fulfill the desired characteristics and are of practical use. 

PMID- 24083109
TI  - Comparison result of inversion of gravity data of a fault by particle swarm
      optimization and Levenberg-Marquardt methods.
AB  - The purpose of this study was to compare the performance of two methods for
      gravity inversion of a fault. First method [Particle swarm optimization (PSO)] is
      a heuristic global optimization method and also an optimization algorithm, which
      is based on swarm intelligence. It comes from the research on the bird and fish
      flock movement behavior. Second method [The Levenberg-Marquardt algorithm (LM)]
      is an approximation to the Newton method used also for training ANNs. In this
      paper first we discussed the gravity field of a fault, then describes the
      algorithms of PSO and LM And presents application of Levenberg-Marquardt
      algorithm, and a particle swarm algorithm in solving inverse problem of a fault.
      Most importantly the parameters for the algorithms are given for the individual
      tests. Inverse solution reveals that fault model parameters are agree quite well
      with the known results. A more agreement has been found between the predicted
      model anomaly and the observed gravity anomaly in PSO method rather than LM
      method. 

PMID- 24083110
TI  - Osteoporosis: are healthcare professionals missing an opportunity.
AB  - OBJECTIVES: The objective of the current study is to analyze different approaches
      of pharmacists and general practitioners towards availability and use of
      osteoporosis prescreening tools and to find out reasons that explain non
      utilization of such tools in clinical practice. SETTINGS: Among General
      practitioners and Community pharmacists in Pulau Penang, Malaysia. METHODOLOGY:
      An explorative cross sectional study was carried out using convenience sampling
      approach. A pre-validated self- administered questionnaire was used to carry out
      the study. A total of 170 healthcare professionals participated in study. MAIN
      OUTCOME: Evaluation of awareness, use and opinions of healthcare professionals
      regarding osteoporosis prescreening tools. RESULTS: Response rate of study was
      56%. The mean age of the participants was 39.00 + 7.89 years. Less than one third
      of participants were familiar with term prescreening tools or Clinical decision
      rules. The only osteoporosis prescreening tool that was recognized and used by
      majority of participants was FRAX. Participants agreed that low level of
      awareness regarding availability of prescreening tools poses hindrance in
      utilization of such tools in clinical practice. Majority of participants showed
      willingness to gain information and use such tools in future. CONCLUSIONS: The
      results of our study demonstrate an urgent need of implementation of osteoporosis
      prescreening tools educational and awareness programs among healthcare
      professionals.

PMID- 24083111
TI  - Expression of PIK3CA, PTEN mRNA and PIK3CA mutations in primary breast cancer:
      association with lymph node metastases.
AB  - PURPOSE: High activity of the intracellular phosphatidylinositol-3 kinase (PI3K)
      pathway is common in breast cancer. Here, we explore differences in expression of
      important PI3K pathway regulators: the activator, phosphatidylinositol-3-kinase
      catalytic subunit alpha (PIK3CA), and the tumour suppressor, phosphatase and
      tensin homolog (PTEN), in breast carcinoma tissue and normal breast tissue.
      Furthermore, we examine whether expression of PIK3CA and PTEN mRNA and occurrence
      of PIK3CA mutations are associated with lymph node metastases in patients with
      primary breast cancer. METHODS: Paired tissue samples of breast carcinoma and
      normal breast tissue were obtained from 175 breast cancer patients at the time of
      primary surgery, of these 105 patients were lymph node positive. Expression of
      PIK3CA and PTEN mRNA was quantified with Quantitative Real Time PCR. Somatic
      mutations in exon 9 and exon 20 of the PIK3CA gene were identified by genotyping.
      RESULTS: Both PIK3CA and PTEN mRNA expression was significantly increased in
      breast carcinoma tissue compared to normal breast tissue (p = 2 * 10(-11)) and (p
      < 0.001), respectively. PIK3CA mutations were present in 68 out of 175 patients
      (39%), but were not associated with PIK3CA expression (p = 0.59). Expression of
      PIK3CA and PTEN mRNA, and PIK3CA mutations in breast carcinomas were not
      associated with presence of lymph node metastases. CONCLUSIONS: The expression of
      PTEN and PIK3CA mRNA is increased in breast carcinoma tissue compared to normal
      breast tissue, and PIK3CA mutations are frequent in primary breast carcinoma,
      however these factors were not associated with lymph node metastases.

PMID- 24083112
TI  - Enzymatic activity of Lactobacillus reuteri grown in a sweet potato based medium
      with the addition of metal ions.
AB  - The effect of metal ions on the enzymatic activity of Lactobacillus reuteri was
      studied. The enzymatic activity was determined spectrophotometrically using the
      corresponding substrate. In the control group, L. reuteri MF14-C, MM2-3, SD2112,
      and DSM20016 produced the highest alpha-glucosidase (40.06 +/- 2.80 Glu U/mL),
      beta-glucosidase (17.82 +/- 1.45 Glu U/mL), acid phosphatase (20.55 +/- 0.74 Ph
      U/mL), and phytase (0.90 +/- 0.05 Ph U/mL) respectively. The addition of Mg(2+)
      and Mn(2+) led to enhance alpha-glucosidase produced by L. reuteri MM2-3 by
      113.6% and 100.6% respectively. alpha-Glucosidase produced by MF14-C and CF2-7F
      was decrease in the presence of K(+) by 65.8 and 69.4% respectively. beta
      Glucosidase activity of MM7 and SD2112 increased in the presence of Ca(2+) (by
      121.8 and 129.8%) and Fe(2+) (by 143.9 and 126.7%) respectively. Acid phosphatase
      produced by L. reuteri CF2-7F and MM2-3 was enhanced in the presence of Mg(2+),
      Ca(2+) or Mn(2+) by (94.7, 43.2, and 70.1%) and (63.1, 67.8, and 45.6%)
      respectively. On the other hand, Fe(2+), K(+), and Na(+) caused only slight
      increase or decrease in acid phosphatase activity. Phytase produced by L. reuteri
      MM2-3 was increase in the presence of Mg(2+) and Mn(2+) by 51.0 and 74.5%
      respectively. Ca(2+) enhanced phytase activity of MM2-3 and DSM20016 by 27.5 and
      28.9% respectively. The addition of Na(+) or Fe(2+) decreased phytase activity of
      L. reuteri. On average, Mg(2+) and Mn(2+) followed by Ca(2+) led to the highest
      enhancement of the tested enzymes. However, the effect of each metal ion on the
      enzymatic activity of L. reuteri was found to be a strain dependent. Therefore, a
      maximized level of a target enzyme could be achieved by selecting a combination
      of specific strain and specific metal ion. 

PMID- 24083113
TI  - Utilisation of Home Laundry Effluent (HLE) as a catalyst for expeditious one-pot
      aqueous phase synthesis of highly functionalised 4-thiazolidinones.
AB  - BACKGROUND: The impact of global warming and associated climate changes have
      built up pressure to focus on the option of green chemistry over traditional one
      for long term sustainability of the environment. Considering the fact, for the
      first time, efficient HLE catalysed expeditious one-pot synthesis of highly
      functionalised 4-thiazolidinones has been developed. RESULTS: These hybrid
      molecules were synthesized in good to excellent yields. The ease of work-up of
      the reactions less time required and mild conditions are notable features of this
      protocol. It was inferred that halogen containing derivatives were well suited to
      this condensation-cyclization reaction with varying rates to afford 4
      thiazolidine derivatives. In general, the substitution on the aldehyde part was
      shown as a main determinant for reaction time and the product yield. CONCLUSION:
      For the first time home laundry effluent (HLE) owing to the surfactant like
      property has been successfully utilised as catalyst for the synthesis of a series
      of novel 4-thiazolidinone derivatives through one pot, three component
      condensation-cyclization reaction. The uniqueness of the present protocol lies in
      the operational simplicity, ability to reduce the demand for organic solvents,
      reduce the energy and carbon footprint, and meet a wide range of economic needs.

PMID- 24083114
TI  - Pituitary gland metastasis from rectal cancer: report of a case and literature
      review.
AB  - Pituitary metastases are unusual complications of malignancies. In about only 2%
      of patients they origin from colorectal cancer (CRC), with breast and lung as the
      most common primary tumors. Nevertheless, some authors reported a recent increase
      of the incidence of metastases in infrequent sites, such as brain or bone,
      arising from gastrointestinal cancers, probably due to the expanded treatment
      options and the resulting improved survival. Here, we report the case of a 54
      year old woman diagnosed with lung metastases from rectal cancer, who, after
      several cycles of radio- and chemotherapy, presented symptoms and signs of
      pituitary disfunction (i.e. diabetes insipidus, hypothyroidism and diplopy). The
      diagnosis of pituitary metastasis from rectal cancer was histologically confirmed
      after surgery. 

PMID- 24083115
TI  - The epidemiology of breast cancer in French Guiana 2003-2006.
AB  - For the first time the incidence and mortality of breast cancer were estimated in
      French Guiana, an overseas French Territory of South America. A certified cancer
      registry collected exhaustive data on breast cancer between 2003 and 2005. The
      age-standardized rate of breast cancer was 47.1 per 100 000 women. The age
      standardized death rate was 11.0 per 100 000 women. Although the standardized
      incidence and death rates were lower than in metropolitan France and South
      America, the ratio between incidence and mortality showed that the prognosis of
      breast cancer in French Guiana was worse than in metropolitan France (23 deaths
      per 100 incident cases versus 17 deaths per 100 incident cases, respectively).
      The demographics of French Guiana, suggests that mass organized screening may
      benefit from lowering the age of its target population. 

PMID- 24083116
TI  - A one-dimensional slope detection approach.
AB  - This paper extends the scale-invariant edge detector to the one-dimensional
      slope. It can accurately detect the slope and estimate its parameters. The method
      has been verified with several mathematical functions, sample sizes, and noise
      levels. A contrast-invariant operator is proposed to suppress noise. The inter
      sample localization and interpolation greatly improve the accuracy. The proposed
      slope detector is also suitable for real-world signals. In additional to above
      mentioned, a threshold formula is developed for the first derivative slope
      detector, and the upper-bound of the filterable noise level is also explored. 

PMID- 24083117
TI  - Atenolol in the prophylaxis of chronic migraine: a 3-month open-label study.
AB  - BACKGROUND: Chronic migraine (CM) is a type of chronic daily headache. CM
      presents a challenge to primary care physicians and neurologists. Any new
      treatment showing efficiency would therefore be of great importance. Atenolol
      together with other beta-blockers is a first-line choice in episodic migraine
      prophylaxis. Clinical findings support the efficacy of atenolol in doses of 50 to
      200 mg/day. METHODS: Here I present an open-label study the aim of which is to
      evaluate the efficacy and tolerability of atenolol (50 mg o.d) for the prevention
      of CM. 19 patients affected by CM were studied. RESULTS: Following a one-month
      run-in period, the patients took atenolol for 3 months. Mean numbers of headache
      days per month were reduced from 20.1 +/- 2.4 during the run-in period to 7.8 +/-
      6.1 by month 1.5 and to 7.1 +/- 5.7 by the 3rd month of treatment (p < 0.0003).
      There was a significant difference between 1.5 months and the 3rd month (p <
      0.006). The severity of attacks was reduced from a mean 2.3 +/- 0.6 to 1.4 +/-
      1.1 (p < 0.010) at 1.5 months. In this, there was no difference between 1.5
      months and the 3rd month. In 5 (29%) of the17 patients who completed the study,
      CM was totally gone during the 3rd month of treatment. No patient was totally
      unresponsive to the drug. Among the patients who completed the study, the
      treatment was well tolerated and the compliance was good. CONCLUSION: Atenolol
      seems to be a safe and effective treatment for CM. Controlled trials are needed
      to confirm the observed results.

PMID- 24083118
TI  - Impact of tumor chronology and tumor biology on lymph node metastasis in breast
      cancer.
AB  - SYNOPSIS: The significance of nodal metastasis in breast cancer is under
      discussion. We investigated the impact of variables of tumor chronology and tumor
      biology on the presence of lymph node metastases. PURPOSE: Lymph node involvement
      is the main prognostic factor in breast cancer. However, it is under discussion
      whether nodal metastasis in breast cancer only reflects the chronological age of
      the tumor or whether it is also a marker of tumor biology. The goal of our study
      was to investigate the impact of variables of tumor chronology and biology on the
      presence of lymph node metastases. METHODS: We performed a retrospective analysis
      of data from 3002 patients with an early invasive breast carcinoma. All patients
      underwent primary surgery at the University Hospitals Leuven between 2001 and
      2009. First, the impact of tumor size on the presence of lymph node metastasis
      was evaluated as the chronological age of a tumor is supposed to be reflected in
      its size. Next, the impact of tumor grade, lymphovascular invasion and the
      hormone receptor status, which are all variables of tumor biology, was studied.
      Logistic regression analyses were performed and the area under the ROC curve
      (AUC) was calculated as a measure of discrimination between logistic regression
      models. RESULTS: Using pathological tumor size the AUC of prediction was 0.67.
      Based on variables of tumor biology, axillary lymph node positivity could be
      predicted with an AUC of 0.68. Combining variables of tumor chronology and
      biology an AUC of 0.74 for the prediction of axillary lymph node (ALN) positivity
      was calculated. CONCLUSIONS: According to our data variables of tumor chronology
      and tumor biology have a similar impact on the presence of lymph node metastasis.

PMID- 24083119
TI  - Real-time imaging with the o-arm for skull base applications: a cadaveric
      feasibility study.
AB  - Introduction Although intraoperative imaging/navigation has established its
      critical role in neurosurgery, its role in cranial base surgery is currently
      limited. Due to issues such as poor bony resolution and accuracy, surgeons have
      to rely on anatomic landmarks that can be distorted by pathology when drilling
      out critical structures. Though originally developed for spinal application, we
      hypothesized that the O-Arm could address the above issues for use in cranial
      base procedures. Methods A cadaveric study was performed in which heads underwent
      a preprocedure scan via the O-Arm, a fluoroscopic device capable of providing
      three-dimensional images through the use of cone-beam technology. Preprocedure
      scans were taken and then registered to a Stealth S7 machine (Medtronic, Inc.,
      Minneapolis, MN, USA). Key cranial base landmarks were identified on these scans
      and then subsequently identified under direct visualization after (1) endoscopic
      endonasal dissection and (2) a middle fossa approach. We then quantified the
      difference in distance between the preplanned and identified structure during
      surgery. This difference was considered the error. Results For anterior cranial
      fossa structures, the mean error was 0.25 mm (anterior septum), 0.27 mm (left
      septum), and 0.32 mm (right septum). For middle fossa structures, the errors
      were: 0.11 mm (foramen spinosum), 0.44 mm (foramen rotundum), and 0.21 mm
      (foramen ovale). Conclusion Based on this preliminary cadaveric study, we feel
      the O-Arm can provide the necessary imaging resolution at the skull base to be
      employed for intraoperative navigation during cranial base approaches (open and
      endoscopic). This study warrants further investigation into its clinical use in
      patients undergoing similar surgical procedures. 

PMID- 24083120
TI  - New dried human amniotic membrane is useful as a substitute for dural repair
      after skull base surgery.
AB  - Objectives Cerebrospinal fluid (CSF) leakage is an undesirable complication of
      skull base surgery. We used dried human amniotic membrane (AM) as a patch graft
      for dural repair to determine its efficacy in preventing CSF leakage. Design
      Frontoparietal craniotomy and removal of dura were performed in 20 Wistar rats. A
      dried AM was placed to cover the dural defect without suturing in 16 animals. In
      four animals, an expanded polytetrafluoroethylene was implanted. At 2 weeks and
      1, 3, and 6 months, histological examination was performed. Dried AM was also
      used as a substitute in 10 patients who underwent skull base surgery, after
      approval by the Ethics Committee of the University of Toyama. Results At 2 weeks
      after implantation, thick connective tissue completely enclosed the dried AM. At
      1 month after implantation, the connective tissue became thin and the implanted
      AM shortened. At 3 and 6 months after implantation, histological examination
      revealed disappearance of the dried AM and formation of membranous tissue. In the
      clinical study, neither CSF leakage nor clinical adverse reactions directly
      related to the dried AM were observed. Conclusion Dried human AM appears to be an
      ideal substitute for dura, since it is replaced by natural tissue. 

PMID- 24083121
TI  - Intraoperative Transcranial Motor-Evoked Potential Monitoring of the Facial Nerve
      during Cerebellopontine Angle Tumor Resection.
AB  - Objective To determine whether transcranial motor-evoked potential (TCMEP)
      monitoring of the facial nerve (FN) during cerebellopontine angle (CPA) tumor
      resection can predict both immediate and long-term postoperative FN function.
      Design Retrospective review. Setting Tertiary referral center. Main Outcome
      Measures DeltaTCMEP (final-initial) and immediate and long-term facial nerve
      function using House Brackmann (HB) rating scale. Results Intraoperative TCMEP
      data and immediate and follow-up FN outcome are reported for 52 patients
      undergoing CPA tumor resection. Patients with unsatisfactory facial outcome (HB
      >2) at follow-up had an average deltaTCMEP of 57 V, whereas those with HB I or II
      had a mean deltaTCMEP of 0.04 V (t = -2.6, p < 0.05.) Intraoperative deltaTCMEP
      did not differ significantly between groups with satisfactory (HB I, II) and
      unsatisfactory (HB > 2) facial function in the immediate postoperative period.
      Conclusion Intraoperative TCMEP of the facial nerve can be a valuable adjunct to
      conventional facial nerve electromyography during resection of tumors at the CPA.
      Intraoperative deltaTCMEP >57 V may be worrisome for long-term recovery of
      satisfactory facial nerve function. 

PMID- 24083122
TI  - Drainage Pathway of the Superior Petrosal Vein Evaluated by CT Venography in
      Petroclival Meningioma Surgery.
AB  - Objectives This study aimed to clarify the drainage location of the superior
      petrosal vein (SPV) in relation to Meckel's cave and the internal acoustic meatus
      (IAM) and to discuss its significance in petroclival meningioma surgery. Design
      Prospective clinical study. Setting Hospital-based. Participants Five patients
      with petroclival meningioma and 50 patients (primarily unruptured supratentorial
      aneurysm patients, with a few hemifacial spasm patients) with no posterior fossa
      lesions. Main Outcome Measures On computed tomography venography (CTV), the
      drainage site was classified into three patterns based on its relationship to
      Meckel's cave and the IAM: Meckel's cave type, Intermediate type, and Meatal
      type. Results In all patients, the SPV was patent and emptied into the superior
      petrosal sinus (SPS). In patients without posterior fossa lesions, 35% had
      Meckel's cave type, 54% had Intermediate type, and 11% had Meatal type. Of the
      five patients with petroclival meningioma, three had Intermediate type, and two
      had Meckel's cave type. Conclusion The SPV is a significant vein that should be
      preserved to prevent venous complications. Preoperative knowledge of the SPV
      drainage site is helpful for planning the approach and preserving the SPV in
      petroclival meningioma surgery. 

PMID- 24083123
TI  - Predictors of visual outcome following surgical resection of medial sphenoid wing
      meningiomas.
AB  - Objective Medial sphenoid wing meningiomas (SWMs) are relatively common tumors
      that are associated with significant morbidity and mortality, primarily from
      their anatomic proximity to many critical neurological and vascular structures. A
      major complication is visual deterioration. This study aimed to identify
      predictors of visual outcome following medial SWM resection. Design
      Retrospective, stepwise multivariate proportional hazards regression analysis.
      Setting Johns Hopkins Hospital. Participants All patients who underwent medial
      SWM resection from 1998 to 2009. Main Outcome Measures Visual function. Results
      Sixty-five medial SWM resections were performed. After multivariate proportional
      hazards regression analysis, preoperative visual decline (relative risk [RR] 95%
      confidence interval [CI]; 13.431 [2.601 to 46.077], p = 0.006), subtotal
      resection (RR [95% CI]; 3.717 [1.204 to 13.889], p = 0.02), and repeat surgery
      (RR [95% CI]; 5.681 [1.278 to 19.802], p = 0.03) were found to be independent
      predictors of visual decline at last follow-up. Tumor recurrence and
      postoperative radiation therapy trended toward, but did not reach statistical
      significance. Conclusion These findings advocate for early and aggressive
      surgical intervention for patients with medial SWMs to maximize the likelihood of
      subsequent visual preservation. This may provide patients and physicians with
      prognostic information that may guide medical and surgical therapy for patients
      with medial SWMs. 

PMID- 24083124
TI  - Dural defect repair in translabyrinthine acoustic neuroma surgery and its
      implications in cerebrospinal fluid leak occurrence.
AB  - Cerebrospinal fluid (CSF) leak is a complication that may occur after
      translabyrinthine (translab) acoustic neuroma (AN) removal. The aim of this study
      is to verify the incidence of CSF leak using two techniques for dural defect
      closure in translab AN surgery and present a new technique for dural repair. A
      retrospective study was held, reviewing charts of 34 patients in a tertiary
      neurotologic referral center. Out of these 34 patients that underwent translab AN
      excision in a 1-year period, 18 had their dural defect repaired using only
      abdominal fat graft and 16 using synthetic dura substitute (SDS) plus abdominal
      fat tissue. One patient (5.5%) in the first group had CSF leak and 1 (6.2%) in
      the second group had CSF leak postoperatively. Our data suggest that there are no
      significant differences in CSF leak rates using both techniques, although studies
      in a larger series must be undertaken to conclude it. We believe that the
      development of some points in the new technique for dural repair can achieve
      better results and reduce the CSF leak incidence in the translabyrinthine
      acoustic neuroma surgery in the near future. 

PMID- 24083125
TI  - Long-term outcome of esthesioneuroblastoma: hyams grade predicts patient
      survival.
AB  - Object Esthesioneuroblastoma (ENB) is a rare malignant neuroendocrine tumor
      originating from the olfactory neuroepithelium in the cribriform plate.
      Controversy still exists regarding the role of pathologic grading (Hyams grade)
      in prognostication. This study was undertaken to describe our experience with ENB
      and assess the role of pathologic grading in patient outcome. Methods This was a
      retrospective, single-institution experience, including 109 patients with ENB
      treated at our institution from 1962 to 2009. Multivariate analysis was performed
      utilizing Cox regression analysis models utilizing age, gender, modified Kadish
      stage, and Hyams grade. Results Mean age was 49 +/- 16 (median 50) years at
      presentation (range 12 to 90 years). Median follow up was 5.1 years. All-cause
      mortality was significantly influenced by Hyams grading in univariate (p = 0.04)
      and multivariate (p = 0.02) analysis, in addition to proven prognostic factors,
      Kadish staging, lymph node metastasis, and age. Median survival was 9.8 years
      compared with 6.9 years with low (grade 1 to 2) versus high (grade 3 to 4) Hyams
      grade. Median overall survival was 7.2 +/- 0.7 years. Conclusion ENB has a
      variable outcome, which is primarily prognosticated by the extent of involvement
      at presentation (Kadish stage and lymph node metastasis) and higher Hyams
      pathologic grade. 

PMID- 24083126
TI  - Microsurgical Relations between Internal Carotid Artery-Posterior Communicating
      Artery (ICA-PComA) Segment Aneurysms and Skull Base: An Anatomoclinical Study.
AB  - Purpose The study of the clinical, anatomic, imaging, and microsurgical
      characteristics of the aneurysms of the internal carotid-posterior communicating
      artery (ICA-PComA) segment and their relationships with the skull base
      structures. Methods The anatomic relationships of PComA with neurovascular
      elements and skull base structures were studied in cadavers. The clinical,
      imaging, and microsurgical findings of 84 microsurgically treated ICA-PComA
      aneurysms compiled in a prospective database were reviewed. Results The most
      important anatomic relations of the PComA and ICA-PComA aneurysms are with the
      oculomotor nerve around the oculomotor triangle that forms the roof of the
      cavernous sinus. Aneurysms of the ICA-PComA are classified according to the
      orientation of the aneurysmal sac in infratentorial, supratentorial, and
      tentorial. Infratentorial aneurysms frequently present with subarachnoid
      hemorrhage (SAH) and oculomotor nerve paralysis. They have relations with skull
      base structures that often make it necessary to totally or partially resect the
      anterior clinoid process (6.7%) or anterior petroclinoid dural fold (15%).
      Supratentorial aneurysms course with SAH and without oculomotor nerve
      involvement, but they often are associated with intracranial hematoma. Conclusion
      ICA-PComA aneurysms have complex anatomic relations. The orientation of the
      aneurysmal fundus induces relevant differences in the anatomic relations,
      clinical presentation, and microsurgical approach to ICA-PComA aneurysms. 

PMID- 24083127
TI  - Endoscopic endonasal access to the jugular foramen: defining the surgical
      approach.
AB  - Introduction The endoscopic endonasal approach to the parapharyngeal space (PPS)
      and jugular foramen is not well defined. We sought to systematically define the
      important landmarks and limitations of this new surgical technique using an
      endoscopic transmaxillary transpterygoid corridor. Methods Endoscopic dissection
      was performed in both sides of two latex-injected cadaver heads. Left-sided
      dissections were facilitated by the addition of a sublabial maxillary antrostomy.
      The pterygopalatine fossa, infratemporal fossa, and PPS were sequentially
      dissected and the endoscopic perspective was examined. Measurements were obtained
      from the surgical orifices to the upper cervical internal carotid artery (ICA)
      and internal jugular vein (IJV). Results Successful access to the PPS and jugular
      foramen was achieved in each dissection. The lateral pterygoid plate, mandibular
      branch of the trigeminal nerve, middle meningeal artery, levator veli palatini
      muscle, Eustachian tube, and stylopharyngeal fascia were identified as landmarks
      for the upper cervical ICA and the IJV. The mean distance from the nasal sill was
      markedly greater than from an ipsilateral sublabial antrostomy. Conclusion The
      endoscopic endonasal approach can provide adequate access to the PPS, carotid
      sheath, and jugular foramen. Multiple landmarks are useful to guide the
      dissection within these deep spaces and may facilitate the clinical application
      of this approach. 

PMID- 24083128
TI  - Endoscopic identification of the pharyngeal (palatovaginal) canal: an overlooked
      area.
AB  - Objective The pharyngeal or palatovaginal canal (PC) is a small tunnel that lies
      between the sphenoid process of the palatine bone and the vaginal process of the
      sphenoid bone. Currently, little endoscopic information is available about this
      region. Design and Setting Endoscopic endonasal cadaveric study. Subjects and
      Methods Twenty sides in 10 adult cadaver heads were studied endoscopically. The
      sphenopalatine foramen (SPF) and the adjacent pterygopalatine fossa were exposed.
      Dissection medial to the vidian canal demonstrated a tunnel that runs
      posteromedially in the sphenoid floor. Endoscopic data were documented.
      Additionally, canal measurements were obtained on 20 sides from coronal CT scans
      of paranasal sinuses. Results The PC was identifiable in 85% of the sides,
      although thickness of its bony wall was variable. The endoscopic relationship of
      the canal and its artery with other landmarks is described. Radiologically, the
      diameter of the PC averaged 1.7 mm, and the mean distance from the PC to the
      vidian canal was 3.78 mm. Conclusion The current study provides a novel
      endoscopic identification of an overlooked canal. The pharyngeal artery can be a
      source of bleeding during extended endoscopic procedures. The PC itself could be
      a place for finger-like projections of anatomically related neoplasms. 

PMID- 24083129
TI  - Harvey Cushing's Treatment of Skull Base Infections: The Johns Hopkins
      Experience.
AB  - Objectives In this report, we review Dr. Cushing's early surgical cases at the
      Johns Hopkins Hospital, revealing details of his early operative approaches to
      infections of the skull base. Design Following institutional review board (IRB)
      approval, and through the courtesy of the Alan Mason Chesney Archives, we
      reviewed the Johns Hopkins Hospital surgical files from 1896 to 1912. Setting The
      Johns Hopkins Hospital, 1896 to 1912. Participants Eleven patients underwent
      operative treatment for suspected infections of the skull base. Main Outcome
      Measures The main outcome measure was operative approach, postoperative
      mortality, and condition recorded at the time of discharge. Results Eleven
      patients underwent operative intervention for infections of the skull base. The
      mean age was 30 years (range: 9 to 63). Of these patients, seven (64%) were
      female. The mean length of stay was 16.5 days (range: 4 to 34). Postoperatively
      eight patients were discharged in "well" or "good" condition, one patient
      remained "unimproved," and two patients died during their admission. Conclusion
      Cushing's careful preoperative observation of patients, meticulous operative
      technique, and judicious use of postoperative drainage catheters contributed to a
      remarkably low mortality rate in his series of skull base infections. 

PMID- 24083130
TI  - Use of Individual-level Covariates to Improve Latent Class Analysis of
      Trypanosoma Cruzi Diagnostic Tests.
AB  - Statistical methods such as latent class analysis can estimate the sensitivity
      and specificity of diagnostic tests when no perfect reference test exists.
      Traditional latent class methods assume a constant disease prevalence in one or
      more tested populations. When the risk of disease varies in a known way, these
      models fail to take advantage of additional information that can be obtained by
      measuring risk factors at the level of the individual. We show that by
      incorporating complex field-based epidemiologic data, in which the disease
      prevalence varies as a continuous function of individual-level covariates, our
      model produces more accurate sensitivity and specificity estimates than previous
      methods. We apply this technique to a simulated population and to actual Chagas
      disease test data from a community near Arequipa, Peru. Results from our model
      estimate that the first-line enzyme-linked immunosorbent assay has a sensitivity
      of 78% (95% CI: 62-100%) and a specificity of 100% (95% CI: 99-100%). The
      confirmatory immunofluorescence assay is estimated to be 73% sensitive (95% CI:
      65-81%) and 99% specific (95% CI: 96-100%).

PMID- 24083131
TI  - Bio-signal and System Modeling: From Image Processing to System Biology.

PMID- 24083132
TI  - Analysis of the behavior of a seizure neural mass model using describing
      functions.
AB  - Neural mass models are computational nonlinear models that simulate the activity
      of a population of neurons as an average neuron, in such a way that different
      inhibitory post-synaptic potential and excitatory post-synaptic potential signals
      could be reproduced. These models have been developed either to simulate the
      recognized neural mechanisms or to predict some physiological facts that are not
      easy to realize naturally. The role of the excitatory and inhibitory activity
      variation in seizure genesis has been proved, but it is not evident how these
      activities influence appearance of seizure like signals. In this paper a
      population model is considered in which the physiological inter-relation of the
      pyramidal and inter-neurons of the hippocampus has been appropriately modeled.
      The average neurons of this model have been assumed to act as a linear filter
      followed by a nonlinear function. By changing the gain of excitatory and
      inhibitory activities that are modeled by the gain of the filters, seizure-like
      signals could be generated. In this paper through the analysis of this nonlinear
      model by means of the describing function concepts, it is theoretically shown
      that not only the gains of the excitatory and inhibitory activities, but also the
      time constants may play an efficient role in seizure genesis. 

PMID- 24083133
TI  - A Hybrid Soft-computing Method for Image Analysis of Digital Plantar Scanners.
AB  - Digital foot scanners have been developed in recent years to yield
      anthropometrists digital image of insole with pressure distribution and
      anthropometric information. In this paper, a hybrid algorithm containing gray
      level spatial correlation (GLSC) histogram and Shanbag entropy is presented for
      analysis of scanned foot images. An evolutionary algorithm is also employed to
      find the optimum parameters of GLSC and transform function of the membership
      values. Resulting binary images as the thresholded images are undergone
      anthropometric measurements taking in to account the scale factor of pixel size
      to metric scale. The proposed method is finally applied to plantar images
      obtained through scanning feet of randomly selected subjects by a foot scanner
      system as our experimental setup described in the paper. Running computation time
      and the effects of GLSC parameters are investigated in the simulation results. 

PMID- 24083134
TI  - A comprehensive comparison of different clustering methods for reliability
      analysis of microarray data.
AB  - In this study, we considered some competitive learning methods including hard
      competitive learning and soft competitive learning with/without fixed network
      dimensionality for reliability analysis in microarrays. In order to have a more
      extensive view, and keeping in mind that competitive learning methods aim at
      error minimization or entropy maximization (different kinds of function
      optimization), we decided to investigate the abilities of mixture decomposition
      schemes. Therefore, we assert that this study covers the algorithms based on
      function optimization with particular insistence on different competitive
      learning methods. The destination is finding the most powerful method according
      to a pre-specified criterion determined with numerical methods and matrix
      similarity measures. Furthermore, we should provide an indication showing the
      intrinsic ability of the dataset to form clusters before we apply a clustering
      algorithm. Therefore, we proposed Hopkins statistic as a method for finding the
      intrinsic ability of a data to be clustered. The results show the remarkable
      ability of Rayleigh mixture model in comparison with other methods in reliability
      analysis task. 

PMID- 24083135
TI  - Monte Carlo Study of Fetal Dosimetry Parameters for 6 MV Photon Beam.
AB  - Because of the adverse effects of ionizing radiation on fetuses, prior to
      radiotherapy of pregnant patients, fetal dose should be estimated. Fetal dose has
      been studied by several authors in different depths in phantoms with various
      abdomen thicknesses (ATs). In this study, the effect of maternal AT and depth in
      fetal dosimetry was investigated, using peripheral dose (PD) distribution
      evaluations. A BEAMnrc model of Oncor linac using out of beam components was used
      for dose calculations in out of field border. A 6 MV photon beam was used to
      irradiate a chest phantom. Measurements were done using EBT2 radiochromic film in
      a RW3 phantom as abdomen. The followings were measured for different ATs: Depth
      PD profiles at two distances from the field's edge, and in-plane PD profiles at
      two depths. The results of this study show that PD is depth dependent near the
      field's edge. The increase in AT does not change PD depth of maximum and its
      distribution as a function of distance from the field's edge. It is concluded
      that estimating the maximum fetal dose, using a flat phantom, i.e., without
      taking into account the AT, is possible. Furthermore, an in-plane profile
      measured at any depth can represent the dose variation as a function of distance.
      However, in order to estimate the maximum PD the depth of D max in out of field
      should be used for in-plane profile measurement. 

PMID- 24083136
TI  - EEG Signature of Object Categorization from Event-related Potentials.
AB  - Human visual system recognizes objects in a fast manner and the neural activity
      of the human brain generates signals which provide information about objects
      categories seen by the subjects. The brain signals can be recorded using
      different systems like the electroencephalogram (EEG). The EEG signals carry
      significant information about the stimuli that stimulate the brain. In order to
      translate information derived from the EEG for the object recognition mechanism,
      in this study, twelve various categories were selected as visual stimuli and were
      presented to the subjects in a controlled task and the signals were recorded
      through 19-channel EEG recording system. Analysis of signals was performed using
      two different event-related potential (ERP) computations namely the "target/rest"
      and "target/non-target" tasks. Comparing ERP of target with rest time indicated
      that the most involved electrodes in our task were F3, F4, C3, C4, Fz, Cz, among
      others. ERP of "target/non-target" resulted that in target stimuli two positive
      peaks occurred about 400 ms and 520 ms after stimulus onset; however, in non
      target stimuli only one positive peak appeared about 400 ms after stimulus onset.
      Moreover, reaction times of subjects were computed and the results showed that
      the category of flower had the lowest reaction time; however, the stationery
      category had the maximum reaction time among others. The results provide useful
      information about the channels and the part of the signals that are affected by
      different object categories in terms of ERP brain signals. This study can be
      considered as the first step in the context of human-computer interface
      applications. 

PMID- 24083137
TI  - A review of algorithms for segmentation of optical coherence tomography from
      retina.
AB  - Optical coherence tomography (OCT) is a recently established imaging technique to
      describe different information about the internal structures of an object and to
      image various aspects of biological tissues. OCT image segmentation is mostly
      introduced on retinal OCT to localize the intra-retinal boundaries. Here, we
      review some of the important image segmentation methods for processing retinal
      OCT images. We may classify the OCT segmentation approaches into five distinct
      groups according to the image domain subjected to the segmentation algorithm.
      Current researches in OCT segmentation are mostly based on improving the accuracy
      and precision, and on reducing the required processing time. There is no doubt
      that current 3-D imaging modalities are now moving the research projects toward
      volume segmentation along with 3-D rendering and visualization. It is also
      important to develop robust methods capable of dealing with pathologic cases in
      OCT imaging. 

PMID- 24083138
TI  - Radiofrequency radiation and human ferritin.

PMID- 24083139
TI  - Will the epidemic of metabolic syndrome raise the prevalence of antiplatelet drug
      resistance?

PMID- 24083141
TI  - Effect of sildenafil-induced nitric oxide on the histomorphology of
      cardiomyocytes in male rats.
AB  - INTRODUCTION: Although sildenafil citrate, one of the selective phosphodiesterase
      5 (PDE5) inhibitors, is considered the best treatment for erectile dysfunction,
      studies have shown that it has also a beneficial effect on a variety of
      cardiovascular conditions. In spite of reports of a significant protective effect
      of sildenafil against necrosis in intact hearts, there are also contradictory
      reports regarding its beneficial effect on the heart. Since there are not enough
      reports regarding the histomorphological changes in the cardiomyocytes after
      exposure to sildenafil citrate, the present study was conducted to observe the
      same along with other biochemical parameters. MATERIALS AND METHODS: Adult male
      albino rats of Wistar strain were used in the present study. The animals were
      divided into a control group and two experimental groups containing six rats
      each. The animals were treated with a solution of sildenafil citrate dissolved in
      distilled water. Histomorphological changes were observed by light microscopy and
      the levels of nitric oxide (NO) and PDE in the heart were measured by
      spectrophotometry. RESULTS: It was observed that animals treated with sildenafil
      citrate showed a highly significant increase in NO and a decrease in PDE level,
      but the histological architecture of the cardiomyocytes did not show much change
      other than a slightly elongated and swollen nucleus. CONCLUSIONS: This study
      shows that sildenafil citrate at low dosage is well tolerated by cardiac muscle
      cells, but as dosage increases, it may become detrimental through its NO and PDE
      activity.

PMID- 24083140
TI  - A novel marker procalcitonin may help stem the antibiotic overuse in emergency
      setting.
AB  - The day the wonder drugs, antibiotics, were available for cure to humans;
      dramatic rise of average life expectancy has been recorded compared to past.
      However, disease-causing microbes that have developed resistance to antibiotics
      are an increasing public health problem. Recently, superbug emergence was
      reported in some countries including India. One of the reasons quoted was misuse
      of antibiotics. Clinical signs and symptoms of infection often do not point
      towards the etiology. The dilemma occurs as diagnosis of sepsis is difficult
      because of nonspecificity of clinical signs and symptoms, and frequent
      overlapping of symptoms with other noninfectious causes of systemic inflammation.
      Key for improving survival rates lies in early diagnosis and treatment. Serum
      procalcitonin (PCT) levels measuring in sick patients during infection may be
      valuable in diagnosing the conditions, and its changing levels have some
      prognostic value too. 

PMID- 24083142
TI  - Evaluating the effectiveness of gel formulation of irradiated seed lectin
      Cratylia mollis during bone repair in rats.
AB  - CONTEXT: Regeneration corresponds to the replacement of damaged cells with ones
      that have the same morphology and function. For experimental evaluation of
      materials that may favor the process of bone healing, defects are created with
      dimensions that prevent spontaneous regeneration. For the development and use of
      new drugs, it is necessary to study its effects in vitro, which depends on the
      formulation, concentration, and rate of irradiation in vivo and the route and
      frequency of administration; thus, it is possible to characterize the
      physiological and molecular mechanisms involved in the response and cellular
      effects. OBJECTIVE: The objective of this study was to assess the effect of
      Cramoll-1,4 on the process of bone repair. MATERIALS AND METHODS: A formulation
      of biopharmaceutical lectin Cramoll-1,4 at a concentration of 300 mg/100 mL was
      applied in a single application via gamma radiation and its effect on the process
      of bone repair in rats was assessed. RESULTS: Histologically, it was observed
      that the bone defect is coated by loose connective tissue rich in fibroblasts,
      providing a range similar to the thick bone original and competing with site of
      new bone formation. This prevented direct contact between the formulation and
      experimental bone tissue, as, despite its proven effectiveness in experiments on
      the repair of skin lesions, the formulation used did not promote bone stimulation
      that would have promoted the tissue repair process. CONCLUSION: Because of the
      direct interference of loose tissue repair that prevented direct contact of the
      implant with the bone interface, the formulation did not promote bone
      stimulation.

PMID- 24083143
TI  - Effect of occupation on lipid peroxidation and antioxidant status in coal-fired
      thermal plant workers.
AB  - BACKGROUND: Air pollution from coal-fired power units is large and varied, and
      contributes to a significant number of negative environmental and health effects.
      Reactive oxygen species (ROS) have been implicated in the pathogenesis of coal
      dust-induced toxicity in coal-fired power plants. AIM: The aim of the study was
      to measure free radical damage and the antioxidant activity in workers exposed to
      varying levels of coal dust. MATERIAL AND METHODS: The study population consisted
      of workers in coal handling unit, turbine unit, and boiler unit (n = 50 each),
      working in thermal power plant; and electricians (n = 50) from same department
      were taken as controls. Lipid peroxidation was measured by malondialdehyde (MDA)
      levels and antioxidant activity was determined by superoxide dismutase (SOD) and
      glutathione peroxidase (GPx) levels. Statistical analysis was carried out by
      Student's unpaired t-test. RESULT: MDA levels showed significant increase (P >
      0.001) in the thermal power plant workers than the electricians working in the
      city. The levels of SOD and GPx were significantly higher (P > 0.001) in
      electricians as compared to subjects working in thermal plant. Among the thermal
      plant workers, the coal handling unit workers showed significant increase (P >
      0.001) in MDA and significant decrease in SOD and GPx than the workers of boiler
      and turbine unit workers. CONCLUSION: Oxidative stress due to increase in lipid
      peroxidation and decrease in antioxidant activity results from exposure to coal
      dust and coal combustion products during thermal plant activities.

PMID- 24083144
TI  - First experience with using simple polymerase chain reaction-based methods as an
      alternative to phenotypic drug susceptibility testing for Myobacterium
      tuberculosis in Iraq.
AB  - CONTEXT: In Iraq, the time-consuming, phenotypic drug susceptibility testing
      (DST) on agar is the sole method available for detecting drug resistance in
      Myobacterium tuberculosis (TB). Furthermore, only single laboratory across Iraq
      is performing it on wide scale. AIMS: To explore utility of rapid, polymerase
      chain reaction (PCR)-based systems in detection of drug resistance in under the
      Iraqi settings. SETTINGS AND DESIGN: Cross-sectional study. A total of 79
      nonduplicated isolates were included in this study. Multiplex allele-specific PCR
      was used to detect mutations at positions 531, 526, and 516 of the rpoB gene. Two
      simplex PCR systems were used to detect mutations in katG3 15 gene and inhAP-15.
      STATISTICAL ANALYSIS USED: Chi-square and crosstabs by SPSS v. 20. RESULTS: On
      DST, out of 69 isolates, 55 isolates were found multidrug-resistant (MDR)-TB; six
      isolates were susceptible to both rifampin (RIF) and isoniazid (INH); two
      isolates were resistant to RIF but not to INH; and six isolates were resistant to
      INH but not RIF. RIF and INH resistance mutations were detected in 50 (90.9%),
      and 43 (78.2%) MDR cases, respectively. Combine resistance mutations to RIF and
      INH were detected in 40 MDR cases (72.7%). The most frequently mutated codon was
      the codon 531 in rpoB gene, mutated in 42 isolates. inhAP-15 and katG315 codons
      were found mutated in 23 and 25 MDR cases (54.8% and 58.1%), respectively. Among
      57 RIF-resistant isolates, 52 (91.2%) were harboring mutations resistance to RIF.
      CONCLUSIONS: These PCR-based methods are potential diagnostic and/or screening
      tools to detect drug-resistance TB in Iraqi settings.

PMID- 24083145
TI  - Heart rate and blood pressure response to exercise and recovery in subclinical
      hypothyroid patients.
AB  - BACKGROUND: Exercise response of asymptomatic subclinical hypothyroid patients
      may aid in early diagnosis of cardiovascular morbidity. AIM: To study and compare
      the heart rate and blood pressure changes during exercise and recovery in
      subclinical hypothyroid patients and euthyroid controls. MATERIALS AND METHODS:
      For the study, 30 each cases (mean age of 40 +/- 7 years) of subclinical
      hypothyroidism and healthy controls underwent exercise as per Bruce protocol.
      Heart rate (HR) and blood pressure (BP) changes were compared every minute (min)
      till 3 min of stage II exercise, continued till maximum heart rate and thereafter
      on recovery, for 5 min after stoppage of exercise. RESULTS: Both groups had
      normal HR and BP at rest, heart rate and BP increased with exercise and remained
      high even after 5 min of recovery from exercise. The increase in systolic blood
      pressure (SBP) with exercise was less in patients at the stage of exercise where
      maximum HR was achieved and up to 1 min of recovery. SBP at 5 min of recovery was
      higher in patients (P = 0.018). Diastolic blood pressure (DBP) increased with
      exercise and changes were similar in both groups during exercise and recovery. HR
      was higher in patients at 1 min of exercise. Changes in HR from 1 min of recovery
      to 2-5 min of recovery were significant in both groups. CONCLUSION: The present
      pilot study highlights that many parameters of HR and SBP during exercise and
      recovery in asymptomatic subclinical hypothyroid patients may differ from
      euthyroid, controls.

PMID- 24083146
TI  - Phytochemical study and screening for antimicrobial activity of flavonoids of
      Euphorbia hirta.
AB  - OBJECTIVE: This study aims to phytochemical and antimicrobial study of Euphorbia
      hirta Euphorbiaceae). MATERIALS AND METHODS: Antimicrobial activity of flavonoids
      (free and bound) of Euphorbia hirta L. was determined by disc diffusion assay
      against four bacteria (Escherichia coli, Pseudomonas aeruginosa, Proteus
      mirabilis, and Staphylococcus aureus) and four fungi (Aspergillus flavus,
      Aspergillus niger, Trichophyton mentagrophytes, and Candida albicans). Minimum
      inhibitory concentration (MIC) of the extract was evaluated through micro broth
      dilution method, while minimum bactericidal/fungicidal concentration was
      determined by subculturing the relevant samples. Total activity (TA) of extracts
      against each sensitive pathogen was also evaluated. RESULTS: Out of fungi; A.
      flavus, A. niger, and T. mentagrophytes were found to be resistant, against which
      none of the tested extracts showed activity. Bound flavonoids extract of root
      showed best activity against C. albicans (inhibition zone (IZ) 27.66, MIC 0.039,
      minimum fungicidal concentration (MFC) 0.039). TA of free flavonoid extract of
      root was found to be the same for P. mirabilis and S. aureus (192.30 ml/g). Two
      flavonoids quercetin and kaempferol were identified in the bound flavonoids of
      stem extract which showed activity against all the microorganisms. CONCLUSION:
      Results of the present investigation indicate that E. hirta has good
      antimicrobial activity with low range of MIC, hence can be exploited for future
      plant-based antimicrobial drugs.

PMID- 24083148
TI  - Acute pancreatitis in pregnancy: A treatment paradigm based on our hospital
      experience.
AB  - BACKGROUND: Acute pancreatitis (AP) is a rare event in pregnancy, occurring in
      approximately 3 in 10 000 pregnancies. The spectrum of AP in pregnancy ranges
      from mild pancreatitis to serious pancreatitis associated with necrosis,
      abscesses, pseudocysts, and multiple organ dysfunction syndromes. As in any other
      disease associated with pregnancy, AP is associated with greater concerns as it
      deals with two lives rather than just one as in the nonpregnant population. AP is
      most often associated with gall stone disease or hypertriglyceridemia. MATERIAL
      AND METHODS: We present 2 years of experience during which we had eight patients
      of AP. RESULTS: Of the eight patients, three underwent laparoscopic
      cholecystectomy and five were treated conservatively. One had multiple cysts in
      the abdomen which were drained. All the patients delivered at term. Prophylactic
      tocolysis was given for 48-72 h to only those patients who had laparoscopic
      cholecystectomy. All the patients recovered completely. There was no maternal or
      fetal mortality. CONCLUSION: When properly managed AP in pregnancy does not carry
      a dismal prognosis as in the past.

PMID- 24083147
TI  - Study of platelet aggregation in acute coronary syndrome with special reference
      to metabolic syndrome.
AB  - BACKGROUND/CONTEXT: Antiplatelet drug resistance increases the risk of adverse
      events like stent thrombosis in acute coronary syndrome (ACS). Metabolic syndrome
      (MS) is a prothrombotic state and presence of MS further increases the risk of
      antiplatelet drug resistance. AIMS AND OBJECTIVES: We studied platelet
      aggregation characteristics in patients of ACS for aspirin or clopidogrel
      resistance. We studied the relation of drug resistance with blood markers like
      high sensitivity C-reactive protein (hsCRP). We also studied for any relation of
      drug resistance with presence of MS. MATERIALS AND METHODS: We studied platelet
      aggregation characteristics by optical aggregometry using platelet-rich plasma
      (PRP) of patients. Collagen (2 MUg/mL) and adenosine diphosphate (ADP; 10 MUmol)
      were used. Greater than 50% aggregation in PRP of patients was taken as an
      evidence of drug resistance. Suitable blood tests were done including newer risk
      markers like hsCRP, apolipoprotein B, and fibrinogen. STATISTICAL TEST:
      Statistical tests included Student's t-test and Kendall's rank correlation
      coefficient. RESULTS: We had a total of 94 patients of ACS with 47 (50%) having
      MS. MS patients showed higher blood levels of hsCRP and fibrinogen. Twenty-eight
      (59.5%) patients with MS showed antiplatelet drug resistance compared to 12
      patients without MS. Serum fibrinogen showed strongest correlation with drug
      resistance. HsCRP levels showed correlation with aspirin resistance (r = 0.53)
      only in the MS group. DISCUSSION AND CONCLUSION: We found significantly high
      prevalence of antiplatelet drug resistance. Aspirin and clopidogrel resistance
      was comparable. MS was a significant risk factor for drug resistance. The
      prothrombotic and proinflammatory markers showed strong correlation with drug
      resistance. A larger randomized trial is needed to better characterize this
      clinical problem.

PMID- 24083149
TI  - Non Peutz-Jegher syndrome associated malignant sex cord stromal tumor with
      annular tubules.
AB  - Sex cord stromal tumor with annular tubules (SCTAT) is a distinctive, rare
      subtype of sex cord stromal tumor of the ovary, predominant component of which
      has morphological features intermediate between that of granulosa cell and
      sertoli cell. The majority of ovarian SCTAT are benign. So far, malignant
      behavior in SCTAT has been reported only in sporadic cases. We have presented a
      case of malignant SCTAT in a 35-year-old lady with no associated Peutz-Jegher (P
      J) syndrome. 

PMID- 24083150
TI  - Giant chondroid syringoma with divergent differentiation: Cyto-histo-immuno
      correlation.
AB  - Chondroid syringoma is a rare benign skin adnexal tumor of eccrine/apocrine
      origin affecting commonly the head and neck region. It is also called as mixed
      tumor of skin because of the presence of both the epithelial and mesenchymal
      components. There are very few case reports of chondroid syringoma diagnosed on
      fine needle aspiration cytology (FNAC). We hereby report a case of giant
      chondroid syringoma occurring over the lower back in a 50-year-old male,
      diagnosed initially on cytology and confirmed by histopathology. This case is
      reported for its unusual size and site of occurrence. We describe the clinical
      features, cytology, histopathology, immunohistochemistry, and differential
      diagnosis of giant chondroid syringoma along with review of literature. 

PMID- 24083151
TI  - Health insurance: Is Indian rural population aware?

PMID- 24083152
TI  - Rhamnolipid production among clinical and skin isolates of healthy individuals of
      Acinetobacter species: The first report.

PMID- 24083153
TI  - Nature identical curcumin.

PMID- 24083154
TI  - Adaptation to vitamin D deficiency: Age specific clinical presentations.

PMID- 24083155
TI  - The intestinal calcistat: Determinant of clinical vitamin D deficiency.

PMID- 24083156
TI  - Defining vitamin D deficiency, using surrogate markers.

PMID- 24083157
TI  - Vulvodynia: An unrecognized diabetic neuropathic syndrome.
AB  - Vulvar pain syndromes, including vulvodynia, are a common source of morbidity in
      women and cause much physical and psychological suffering. This brief
      communication postulates the hypothesis that unexplained vulvar pain may be
      hitherto undescribed manifestation of painful sensory diabetic neuropathy. It
      describes the clinical characteristics of vulvodynia and highlights the
      similarities between this condition and diabetic neuropathy. The hypothesis calls
      for women presenting with vulvar pain to be screened for diabetes, as well as
      women with diabetes to be questioned about vulvar symptomatology. The paper hopes
      to stimulate extensive research in this important, but so far neglected, field of
      women's endocrine health. 

PMID- 24083158
TI  - Reproductive outcomes of female patients with congenital adrenal hyperplasia due
      to 21-hydroxylase defi ciency.
AB  - Fertility in women with congenital adrenal hyperplasia (CAH) due to 21
      hydroxylase deficiency (21-OHD) appears to be reduced, especially in women with
      the classic salt-wasting type. Several factors have been suggested to contribute
      to this subfertility such as androgen excess, adrenal progesterone
      hypersecretion, consequences of genital reconstructive surgery, secondary
      polycystic ovaries syndrome, and psychosexual factors. In contrast to this
      subfertility, pregnancies are commonly normal and uneventful. Adequate
      glucocorticoid therapy and improvement of surgical and psychological management
      could contribute to optimize fertility in CAH female patients, even among women
      with the classic variant. This review provides current information regarding the
      reproductive outcomes of women with CAH due to 21-OHD and the fertility and
      pregnancy issues in this population. 

PMID- 24083159
TI  - The other side of Turner's: Noonan's syndrome.
AB  - Noonan Syndrome (NS) is an autosomal dominant disorder characterized by short
      stature, typical face dysmorphology, and congenital heart defects. NS is a
      clinical diagnosis. Establishing the diagnosis can be very difficult, especially
      in adulthood. There is a great variability in expression, and the phenotype
      becomes less pronounced with increasing age. 

PMID- 24083160
TI  - Metabolic pancreatitis: Etiopathogenesis and management.
AB  - Acute pancreatitis is a medical emergency. Alcohol and gallstones are the most
      common etiologies accounting for 60%-75% cases. Other important causes include
      postendoscopic retrograde cholangiopancreatography procedure, abdominal trauma,
      drug toxicity, various infections, autoimmune, ischemia, and hereditary causes.
      In about 15% of cases the cause remains unknown (idiopathic pancreatitis).
      Metabolic conditions giving rise to pancreatitis are less common, accounting for
      5%-10% cases. The causes include hypertriglyceridemia, hypercalcemia, diabetes
      mellitus, porphyria, and Wilson's disease. The episodes of pancreatitis tend to
      be more severe. In cases of metabolic pancreatitis, over and above the standard
      routine management of pancreatitis, careful management of the underlying
      metabolic abnormalities is of paramount importance. If not treated properly, it
      leads to recurrent life-threatening bouts of acute pancreatitis. We hereby review
      the pathogenesis and management of various causes of metabolic pancreatitis. 

PMID- 24083161
TI  - Emerging risk factors for cardiovascular diseases: Indian context.
AB  - Cardiovascular disease (CVD) is globally considered as the leading cause of death
      with 80% of CVD related deaths being reported from low and middle income
      countries like India. The relatively early onset age of CVD in India in
      comparison to Western countries also implies that most productive ages of the
      patient's life are lost fighting the disease. Conventional cardiovascular risk is
      attributed to lifestyle changes and altered metabolic activity. This forms the
      basis of a 10-year risk prediction score inspired by the Framingham study. Since
      South Asians display considerable heterogeneity in risk factors as compared to
      developed countries, there is a need to identify risk factors which would not
      only help in primary prevention but also prevent their recurrence. We reviewed
      published data on novel risk factors and their potential to identify
      cardiovascular risk at an early stage, with special emphasis on the Indian
      population. Emerging risk factors were reviewed to identify their potential to
      prevent CVD progression independently as well as in association with other
      cardiovascular risk factors. The most commonly studied emerging cardiovascular
      risk factors included coronary artery calcium score, lipoprotein (a),
      apolipoproteins, homocysteine, thrombosis markers like fibrinogen, and
      plasminogen activator inhibitor 1, carotid intima-media thickness, genotypic
      variations, non-alcoholic fatty liver disease, C-reactive protein, platelets, and
      birth weight levels. Nonetheless, more studies on large sample size can ascertain
      the utility of these risk factors in estimation and analysis of cardiovascular
      risk especially in the Indian context. 

PMID- 24083162
TI  - Psychosocial management of diabetes in pregnancy.
AB  - This consensus based national guideline addresses the need for psychological,
      psychiatric and social assessment, as well as management, in antenatal women with
      diabetes. It builds upon the earlier Indian guidelines on psychological
      management of diabetes, and should be considered as an addendum to the parent
      guideline. 

PMID- 24083164
TI  - Importance of achieving the composite endpoints in diabetes.
AB  - Well-conducted randomized controlled trials are instrumental in providing vital
      data on safety and efficacy of new molecules under consideration for approval.
      However acquiring such data involves huge cost and focused scientific endeavor.
      Selection and reporting of endpoints of a therapy is essential to assess the
      effect(s) of an intervention on overall disease control and guidelines have
      suggested the use of composite endpoint (CEP) in clinical trial design over
      individual endpoints to demonstrate the compound effect. Composite endpoints have
      been preferred for their ability to assess the net clinical benefit of an
      intervention, avoid misinterpretation associated with competing risks, avoid the
      challenge of using a single outcome to validate the study objectives and reduce
      the sample size requirements in trials on patients treated for diabetes. Concerns
      for misinterpretation or difficulty in interpretation of trial results involving
      CEPs arise when differences in the components with respect to either clinical
      importance or event rates, or magnitude of treatment effect exist and when
      there's a possibility of biases due to competing risk. Suggestions for
      construction of composite endpoints and reporting the results of trials involving
      CEPs have been presented to improve the interpretations of overall effect of new
      interventions. 

PMID- 24083163
TI  - Hypoglycemia: The neglected complication.
AB  - Hypoglycemia is an important complication of glucose-lowering therapy in patients
      with diabetes mellitus. Attempts made at intensive glycemic control invariably
      increases the risk of hypoglycemia. A six-fold increase in deaths due to diabetes
      has been attributed to patients experiencing severe hypoglycemia in comparison to
      those not experiencing severe hypoglycemia Repeated episodes of hypoglycemia can
      lead to impairment of the counter-regulatory system with the potential for
      development of hypoglycemia unawareness. The short- and long-term complications
      of diabetes related hypoglycemia include precipitation of acute cerebrovascular
      disease, myocardial infarction, neurocognitive dysfunction, retinal cell death
      and loss of vision in addition to health-related quality of life issues
      pertaining to sleep, driving, employment, recreational activities involving
      exercise and travel. There is an urgent need to examine the clinical spectrum and
      burden of hypoglycemia so that adequate control measures can be implemented
      against this neglected life-threatening complication. Early recognition of
      hypoglycemia risk factors, self-monitoring of blood glucose, selection of
      appropriate treatment regimens with minimal or no risk of hypoglycemia and
      appropriate educational programs for healthcare professionals and patients with
      diabetes are the major ways forward to maintain good glycemic control, minimize
      the risk of hypoglycemia and thereby prevent long-term complications. 

PMID- 24083166
TI  - Progression of puberty after initiation of androgen therapy in patients with
      idiopathic hypogonadotropic hypogonadism.
AB  - BACKGROUND: Onset of puberty in boys usually occurs by 14 years of age. Some boys
      may exhibit delayed sexual maturation till about 17-18 years of age. However,
      pubertal onset beyond 18 years of age is exceedingly rare. MATERIALS AND METHODS:
      Patients diagnosed as idiopathic hypogonadotropic hypogonadism (IHH) who had
      onset of puberty (increase in testicular volume >10 ml) while on androgen therapy
      were studied. These patients were evaluated prospectively. RESULTS: There were
      nine subjects that were included in the study. The pre-therapy testicular volumes
      ranged from 3 to 6 ml. Luteinizing hormone (LH) levels increased from 1.2 +/-
      0.96 to 2.8 +/- 1.0 IU/L, follicular stimulating hormone (FSH) levels increased
      from 1.5 +/- 0.79 to 3.5 +/- 1.9 IU/L, and testosterone increased from 0.36 +/-
      0.16 to 3.4 +/- 2.1 ng/ml. Three out of nine patients had testosterone levels
      below 3 ng/ml. CONCLUSION: Our present study indicates that pubertal development
      can occur in patients presenting with hypogonadotropic hypogonadism after 18
      years of age. However, acquired pubertal status may be subnormal.

PMID- 24083165
TI  - Differences in traditional and non-traditional risk factors with special
      reference to nutritional factors in patients with coronary artery disease with or
      without diabetes mellitus.
AB  - INTRODUCTION: There is an increase in awareness about the role of nutritional
      factors in chronic non-communicable diseases. We therefore conducted this study
      with an aim to assess the relationship between nutritional factor (vitamin B12
      and homocysteine [Hcy]) and its association with insulin resistance and
      inflammatory markers, and differences in traditional and non-traditional risk
      factors among diabetics and non-diabetics in known cases of coronary artery
      disease (CAD). MATERIALS AND METHODS: Three hundred consecutive patients with
      known coronary disease on coronary angiography, who were >25 years old were
      included in this study. All cases were interviewed using a questionnaire. Blood
      samples were analyzed for insulin, vitamin B12, Hcy and inflammatory markers
      (highly sensitive C-reactive protein [hsCRP], interleukin-6 [IL-6], Tumor
      necrosis factor-alfa [TNF-alpha]). Insulin resistance was calculated with
      homeostasis model assessment of insulin resistance (HOMA-IR). RESULTS: Mean age
      of the patients was 60.95 +/- 12.3 years. Body mass index and waist hip ratio
      were comparable in both groups. Triglyceride, very low-density lipoprotein and
      HbA1C were significantly higher and high-density lipoprotein (HDL) was
      significantly lower in patients with diabetes. Patients with diabetes had
      significantly high levels of IL-6, hsCRP and TNF-alpha compared with non-diabetic
      patients. Insulin resistance was twofold higher in diabetic patients. Serum
      vitamin B12 levels were significantly lower and Hcy was significantly higher in
      the diabetic group compared with the non-diabetic patients. HbA1C, HOMA-IR and
      Hcy levels were positively correlated with inflammatory markers in the total
      study population and in the non-diabetic patients; but, in diabetic patients,
      HbA1C and Hcy showed this relation. CONCLUSIONS: Vitamin B12 deficiency is common
      in the diabetic population. Hcy levels were higher in diabetics compared with non
      diabetics, and were related to glycemic level and insulin resistance in diabetic
      patients. Patients with diabetes had higher traditional risk factors than
      patients without diabetes in known patients with CAD. Glycemic status was
      associated with insulin resistance and inflammatory markers.

PMID- 24083168
TI  - Evaluation of skin and subcutaneous tissue thickness at insulin injection sites
      in Indian, insulin naive, type-2 diabetic adult population.
AB  - CONTEXT: Skin thickness of type-2 diabetic insulin naive adult patients.
      BACKGROUND: We have limited data on skin and subcutaneous tissue thickness of
      Indian type-2 diabetic population. Objective of this study was to assess skin and
      subcutaneous tissue thickness in insulin naive type-2 diabetic patients as this
      information may be useful for insulin injection technique. AIMS: To assess the
      skin and subcutaneous tissue thickness at insulin injection sites in insulin
      naive, type-2 diabetic adult population across different body mass index (BMI).
      SETTINGS AND DESIGN: Observational study carried out at our institute. MATERIALS
      AND METHODS: One hundred and one insulin naive type-2 diabetic subjects underwent
      skin thickness measurement using ultrasound at insulin administration sites. Skin
      and subcutaneous tissue thickness were measured and prints taken. Though, the
      sample size to be taken for the study was not calculated, the results obtained
      clearly show that the power of the study was 80%. RESULTS: At arm and thigh, the
      mean skin thickness was more in males as compared to females in the BMI range <23
      kg/m(2) (P < 0.05). At abdomen, skin thickness was more in males in the BMI range
      19-23 kg/m(2) (P < 0.05). Across all the BMIs, mean skin plus subcutaneous
      thickness at arm was more in females (P < 0.05) except for BMI >25 kg/m(2) where
      thickness in males was comparable. At thigh, the skin plus subcutaneous tissue
      thickness was more in females (P < 0.05), across all BMI ranges. At abdomen,
      thickness was more in females for the BMI ranges 17-19 kg/m(2) and 23-25 kg/m(2),
      while it was comparable across all other BMI ranges (P > 0.05). CONCLUSIONS: Skin
      and subcutaneous tissue thickness can be estimated by BMI. In general it is
      higher in females.

PMID- 24083167
TI  - Endocrine complications after busulphan and cyclophosphamide based hematopoietic
      stem cell transplant: A single tertiary care centre experience.
AB  - INTRODUCTION: Endocrine complications are common after hematopoietic stem cell
      transplant (HSCT). Although HSCT is performed at various centers in India, no
      study is available for endocrine dysfunctions among them. This study was carried
      out with the objective to evaluate endocrine dysfunction among patients undergone
      HSCT in the past. MATERIALS AND METHODS: We carried out a cross-sectional study
      in a 50 post-HSCT recipients (39 allogenic, 11 autologous). All relevant data
      were collected from patient's records. Samples for hormonal estimation were
      collected and stimulation tests for cortisol and growth hormone were interpreted
      based on peak values achieved during insulin tolerance test. RESULTS: The mean
      age of patients was 26.3 +/- 16.9 years (range 4-74). Adrenal insufficiency (AI)
      was present in 60%, hypergonadotropic hypogonadism (HH) in 60%, growth hormone
      deficiency (GHD) in 54%, hypothyroidism in 4%, hyperprolactinemia in 4%, new
      onset diabetes after transplant in 4%, and impaired fasting glucose in 6%.
      Multiple endocrine complications were common. GHD was present in 77% of children
      (n = 22) although height standard deviation score was not statistically different
      compared to those who didn't have GHD. HH was present in 36% of children. In
      adults (n = 28), 36% had GHD, all females had HH, and 89% of males had HH. Germ
      cell dysfunction with compensated Leydig cell dysfunction was the most common
      pattern of HH in males. Fifteen patients had graft versus host disease (GVHD).
      GVHD had no bearing on development of endocrine deficiencies. AI was related to
      duration after and type of transplant, but was unrelated to steroid intake.
      CONCLUSIONS: Endocrine manifestations are common after HSCT; they can occur as
      early or late complications. All HSCT recipients should have endocrine evaluation
      as per prevailing guidelines.

PMID- 24083169
TI  - Bibliometric analysis of Indian Journal of Endocrinology and Metabolism.
AB  - BACKGROUND: Bibliometric analysis of the journal is a method to assess the
      research impact or research influence of that journal. This information can also
      be used to evaluate the influence/performance of a researcher and to provide a
      comparison between researchers. This work was aimed at performing bibliometric
      analysis of Indian Journal of Endocrinology and Metabolism (IJEM). MATERIALS AND
      METHODS: The publications of year 2011-12 of IJEM were analyzed. Total number of
      articles published, type of articles, their authorship, and the coverage of
      various subspecialties was studied. The publications were also classified as
      Indian or foreign, from endocrine or nonendocrine departments and from academic
      or nonacademic institutions according to the institution of first author. RESULTS
      AND CONCLUSIONS: A total of 10 main issues and 7 supplementary issues were
      published in IJEM in year 2011 and 2012. These included a total of 605
      publications, which depict a dramatic increase in the number of publications in
      last 2 years as compared to the previous years. Taking collectively, review
      articles were published in majority. Maximum number of articles was dealing with
      pancreas and metabolic disorders followed by thyroid. Other endocrine organs were
      given almost similar importance. Publications were largely originating from
      endocrine departments and from academic institutions. Although maximum number of
      articles were from India, but the publications from other countries are also on
      an increase. Thus, the widespread coverage of this journal suggests that IJEM has
      begun to represent global face of Indian endocrinology.

PMID- 24083170
TI  - Evaluation of left ventricular mass and function, lipid profile, and insulin
      resistance in Egyptian children with growth hormone deficiency: A single-center
      prospective case-control study.
AB  - BACKGROUND: Growth hormone deficiency (GHD) in adults is associated with a
      cluster of cardiovascular risk factors that may contribute to an increased
      mortality for cardiovascular disease. In children, relatively few studies have
      investigated the effect of GHD and replacement therapy on cardiac performance and
      metabolic abnormalities that may place them at a higher risk of cardiovascular
      disease (CVD) at an early age. AIM: This study was aimed to assess the left
      ventricular function, lipid profile, and degree of insulin resistance in Egyptian
      children with GHD before and after 1 year of GH replacement therapy. SETTINGS AND
      DESIGN: Prospective case-control study, single-center study. MATERIALS AND
      METHODS: Thirty children with short stature due to GHD were studied in comparison
      to 20 healthy age- and sex-matched children. All subjects were subjected to
      history, clinical examination, auxological assessment, and echocardiography to
      assess the left ventricular function. Blood samples were collected for measuring
      IGF-1, lipid profile (Total, LDL, HDL cholesterol, triglyceride, and atherogenic
      index (AI), fasting blood sugar, and fasting insulin levels. In addition, basal
      and stimulated GH levels were measured in children with suspected GHD.
      STATISTICAL ANALYSIS USED: Student's t-test was used for parametric data, and the
      Mann-Whitney U-test was used for non-parametric data. RESULTS: Total, LDL
      cholesterol, triglyceride, AI, and insulin were significantly higher in children
      with GHD than in healthy controls at baseline. After 12 months of GH replacement
      therapy, total, LDL cholesterol, triglyceride, AI and insulin were significantly
      decreased, while homeostatic model assessment for insulin resistance index (HOMA
      IR) was significantly increased compared to both pre-treatment and control
      values. At baseline, the left ventricular mass (LVM) and left ventricular mass
      index (LVMi) were significantly lower in GHD children than in controls. After 12
      months of GH replacement therapy, LVM and LVMi in GHD patients were significantly
      increased compared to pre-treatment values. CONCLUSIONS: GHD in children is
      associated with a significantly reduced cardiac mass and impairment of lipid
      profile. GH replacement therapy exerts beneficial effects both on cardiac mass
      and lipid metabolism by normalizing cardiac size and improving the lipid profile.
      On the contrary, an increase in insulin resistance is observed after 12 months GH
      treatment. The study suggests that children with GH deficiency should have
      echocardiography and lipid profile monitoring before and during treatment with
      GH.

PMID- 24083171
TI  - Effect of two different doses of oral cholecalciferol supplementation on serum 25
      hydroxy-vitamin D levels in healthy Indian postmenopausal women: A randomized
      controlled trial.
AB  - AIM: To compare the effect of two different doses (500 and 1000 IU/day) of oral
      vitamin D3 (cholecalciferol) on serum 25-hydroxy vitamin D [25(OH)D] levels in
      apparently healthy postmenopausal Indian women. MATERIALS AND METHODS: Serum
      25(OH)D, calcium with albumin, phosphorus, and alkaline phosphatase were measured
      in 92 apparently healthy postmenopausal women. The subjects were randomly
      assigned to one of the three groups and received supplementation for 3 months
      each. Each group received 1000 mg calcium carbonate daily while groups B and C
      received 500 and 1000 IU of cholecalciferol in addition, respectively. The tests
      were repeated after 3 months. RESULTS: At baseline, 83.7% subjects had vitamin D
      deficiency (<=20 ng/mL). The difference in the percentage change in mean serum
      25(OH)D levels from baseline in group A (-30.5 +/- 5.3%), group B (+8.9 +/-
      19.7%), and in group C (+97.8 +/- 53.3%) was statistically significant (P <
      0.001) between the three groups. Serum 25(OH)D level >20 ng/mL was achieved in
      4.7% (1/21), 16% (4/25), and 66.67% (12/18) subjects in groups A, B, and C,
      respectively. No significant change was found in serum calcium, phosphorus, and
      alkaline phosphatase levels at 3 months in either of the groups from baseline.
      CONCLUSIONS: Standard dose of cholecalciferol available in "calcium tablets" (250
      IU per 500 mg calcium carbonate) is not adequate for achieving optimum serum
      25(OH)D levels in Indian postmenopausal women. Higher dose of vitamin D
      supplementation with 1000 IU/day (500 IU per 500 mg calcium carbonate) daily is
      superior to the standard dose therapy. For achievement of optimum serum 25(OH)D
      levels (>30 ng/mL) in Indian postmenopausal women, still higher doses of vitamin
      D are likely to be required.

PMID- 24083172
TI  - Association of metabolic syndrome with schizophrenia.
AB  - BACKGROUND: Metabolic syndrome (MetS) is associated with mental illnesses. It is
      a major predictor of mortality and morbidity in patients of such mental
      illnesses. This study was undertaken to study the association of MetS and
      schizophrenia. OBJECTIVES: To study the association of MetS in patients of
      schizophrenia. MATERIALS AND METHODS: Adult schizophrenic patients diagnosed as
      per Diagnostic and Statistical Manual -IV Third R evisioncriteria visiting the
      psychiatric Out Patient Day during the study period were evaluated for prevalence
      of MetS as per the criteria of the international diabetes federation. Fifty
      patients of schizophrenia with age-and sex-matched 50 controls were enrolled for
      the study. RESULTS: MetS was found to be 28% in patient group and 12% in control
      group (P < 0.05). Fourteen patients were found to have MetS out of 38 patients
      who were on antipsychotics for >6 months. All the 14 patients having MetS were
      taking second-generation antipsychotics (SGAs) (P < 0.05). CONCLUSION: The study
      showed a higher prevalence of MetS in schizophrenia than in general population.
      MetS was present only in patients taking SGAs and prevalence of MetS had a
      positive correlation with duration of treatment. The study points toward urgent
      need for consultation - liaisoning between Diabetologist and Psychiatrists.

PMID- 24083173
TI  - Evaluation of only the chin or lower abdomen for predicting hirsutism.
AB  - BACKGROUND: Hirsutism is defined as the growth of terminal hair in a male pattern
      in women; it affects 5-15% of women. OBJECTIVE: The aim of this study is
      evaluation of only the chin or lower abdomen for predicting hirsutism. MATERIALS
      AND METHODS: In this cross-sectional diagnostic study, we randomly selected 695
      women aged 15-45 years. The examiners scored the subjects on a scale of 0 - 4 for
      terminal hair growth on nine different body areas according to the Ferriman
      Gallwey (FG) scoring system in a form given to the examiners before the
      examination. An FG score of 8 or more was considered diagnostic of hirsutism. If
      the sum of the FG scores for the chin or lower abdomen was 2 or more, the test
      result was assumed to be positive. Statistical analysis was performed using the
      MacNemar test, and a P value of less than 0.05 was considered to be statistically
      significant. RESULTS: The age group with the highest prevalence rate was 21-25
      years. From the 695 subjects examined, 81 subjects (11.7%) had an FG score of 8
      or more with a resultant prevalence rate of 11.7% for hirsutism. In our study
      population, 39% of the patients had an FG score of 2 or more for the chin or
      lower abdomen, and 61% of the patients had an FG score of less than 2 for the
      chin or lower abdomen. CONCLUSION: Evaluating terminal hair growth on the chin or
      lower abdomen for predicting hirsutism seems to be an acceptable screening
      method.

PMID- 24083174
TI  - Determinants of developing diabetes mellitus and vascular complications in
      patients with impaired fasting glucose.
AB  - AIMS: To detect the risk factors of diabetes mellitus (DM) and cardiovascular
      complications in subjects with impaired fasting glucose (IFG). MATERIALS AND
      METHODS: One hundred and twenty three subjects with proved IFG in Zanjan Healthy
      Heart Study (2002-2003) were recalled and participated in this study (2009-2010).
      Demographic and laboratoryinformation of the participants were collected.Ischemic
      heart disease (IHD) was assessed by the exercise tolerance test (ETT). All the
      subjects with abnormal ETT or documented past history of IHD confirmed by
      angiographic evaluation. Ophthalmic complications including cataract, glaucoma,
      and diabetic retinopathy were estimated by an ophthalmologist. RESULTS: Incidence
      of DM was 19.5%. All the diabetic and pre-diabetic patients had at least one of
      the other components of metabolic syndrome. Obesity (P: 0.04, OR: 1.8, 95%CI: 1.2
      9) and low physical activity (P < 0.001, OR: 9.6, 95%CI: 3.4-32) were the only
      independent prognostic risk factors for progression to DM in patients with IFG.
      Total incidence of IHD was 14.6% and had a strong correlation with sex (P: 0.01,
      OR: 1.8, 95%CI: 1.2-1.5), age (P < 0.001, OR: 23, 95%CI: 2.1-67) and cigarette
      smoking (P < 0.001, OR: 36.5, 95%CI: 3.9-337). Non-proliferative diabetic
      retinopathy was shown in 2 (1.6%) subjects who were all women. CONCLUSION:
      Obesity and low physical activity are the main factors of developing DM and its
      macrovascular complications in subjects with IFG.

PMID- 24083175
TI  - Comparison of the world health organization and the International association of
      diabetes and pregnancy study groups criteria in diagnosing gestational diabetes
      mellitus in South Indians.
AB  - AIM: We aimed to compare the International Association of Diabetes and Pregnancy
      Study Groups (IADPSG) and the World Health Organization (WHO) criteria to
      diagnose gestational diabetes mellitus (GDM) in Chennai, India. MATERIALS AND
      METHODS: We reviewed the retrospective data of 1351 pregnant women who underwent
      screening for GDM at four selected diabetes centers at Chennai (three private and
      one government). All women underwent an oral glucose tolerance test using 75g
      glucose load and fasting, 1-h, and 2-h samples were collected. The IADPSG and WHO
      criteria were compared for diagnosis of GDM. RESULTS: A total of 839 women had
      GDM by either the IADPSG or the WHO criteria, of whom the IADPSG criteria
      identified 699 and the WHO criteria also identified 699 women as having GDM.
      However, only 599/839 women (66.6%) were identified by both criteria. Thus,
      140/839 women (16.7%) were missed by both the IADPSG and the WHO criteria.
      687/699 (98.2%) of the women with GDM were identified by the WHO criteria. In
      contrast, each value of IADPSG criteria i.e., fasting, 1 h, and 2 h identified
      only 12.5%, 14%, and 22%, respectively. CONCLUSIONS: A single WHO cut-point of 2
      h > 140 mg/dl appears to be suitable for large-scale screening for GDM in India
      and other developing countries.

PMID- 24083176
TI  - Anesthetic techniques and parathyroid hormone levels: Predictor of surgical
      decisions.
AB  - Endocrine surgeries have always been challenging and throw numerous challenges to
      the surgeons, anesthesiologists, and the endocrinologists. A thorough knowledge
      of the pathophysiological aspects associated with endocrinopathies is mandatory
      for the attending anesthesiologist. Parathyroid surgery is a very delicate
      procedure that requires immense and meticulous preparation during the
      perioperative period for achieving a clinical outcome. Parathyroid hormone (PTH)
      levels during intra-operative period can influence the decision making in
      surgery. Anesthetic techniques also play a significant role in the secretion of
      PTH during perioperative period, which can be decisive in re-assessment of
      surgical procedure on operation table. The present communication briefly outlines
      the various anesthetic techniques, which influence the secretion of PTH and also
      influence surgical decision making. 

PMID- 24083177
TI  - Glucocorticoid-induced myopathy: Pathophysiology, diagnosis, and treatment.
AB  - Glucocorticoid-induced myopathy is the most common type of drug-induced myopathy.
      Nearly 60% of patients with Cushing's syndrome have muscle weakness.
      Glucocorticoid-induced muscle atrophy affects mainly fast-twitch glycolytic
      muscle fibers (type IIb fibers). This brief review will discuss the
      pathophysiology behind glucocorticoid-induced myopathy, along with diagnostic
      features and treatment. 

PMID- 24083178
TI  - Pancreatic paraganglioma: An extremely rare entity and crucial role of
      immunohistochemistry for diagnosis.
AB  - Paragangliomas are rare neuroendocrine neoplasms arising in extra-adrenal
      chromaffin cells of autonomic nervous system and histologically akin to
      chemodectomas. They are rare, affecting about 1 in 2,000,000 population. It is a
      generic term applied to tumors of paraganglia regardless of the location. In rare
      instances, paragangliomas present around and involve the pancreas, thereby
      mimicking any one of the more common primary pancreatic lesions. Pancreatic
      paraganglioma is an extremely rare tumor. It grows slowly, so radical resection
      is recommended to achieve curability with good prognosis. These neoplasms present
      considerable diagnostic difficulty not only for the clinician and radiologist but
      also for the pathologist. Here, we report a case of a 55-year-old woman who
      presented with a left-sided abdominal swelling for 3 months duration, initially
      having clinical suspicion of an ovarian tumor. The radiological imaging revealed
      a lesion in the tail of pancreas with a differential diagnosis of pancreatic
      carcinoma and metastatic tumor. Only after exploratory laparotomy, the diagnosis
      was made as a rare case of pancreatic paraganglioma on the basis of histological
      examination and immunohistochemistry. 

PMID- 24083179
TI  - A young diabetic with suicidal risk: Rare disease with a rarer presentation.
AB  - Rare genetic or inherited forms of diabetes can mimic immune mediated type 1
      diabetes. Early age of onset and associated features help to differentiate these
      diseases from type 1 diabetes. Wolfram syndrome, an inherited neuro degenerative
      disorder, presents as insulin dependent diabetes mellitus, diabetes insipidus,
      optic atrophy and deafness. But less well described features like psychiatric
      manifestations can be the presentation of this disease. We present such a case.
      Wolfram syndrome should be considered as a differential diagnosis in insulin
      dependent diabetic children who present with neuropsychiatric problems. 

PMID- 24083180
TI  - Acute mania after thyroxin supplementation in hypothyroid state.
AB  - The current literature variedly ascribes depressive and manic symptoms to hypo-
      and hyperthyroid state, respectively, reporting mania in hypothyroidism as an
      unusual entity. More unusual is precipitation of manic state in hypothyroid
      subjects after thyroxine supplementation for which studies report otherwise
      treating manic symptoms in hypothyroid state with thyroxine. We report a case of
      a patient whose acute mania appears to have been precipitated by thyroxine
      supplementation in hypothyroidism state. This case underscores the importance of
      thyroid screening in patients with mood and psychotic disorders, as well as the
      potency of thyroxine in producing manic symptoms. 

PMID- 24083181
TI  - Short fourth and fifth metacarpals in a case of idiopathic primary
      hypoparathyroidism.
AB  - Shortening of metacarpals is a useful diagnostic marker in patients with
      pseudohypoparathyroidism type Ia (PHP-Ia) with Albright's hereditary
      osteodystrophy (AHO) phenotype or pseudopseudohypoparathyroidism (PPHP). There
      are very rare reports of metacarpals shortening in idiopathic primary
      hypoparathyroidism (IPH) cases in the literature. Here we described a young woman
      with IPH who presented with hypocalcaemia and generalized tonic-clonic seizure.
      She had shortening of forth and fifth metacarpals which was prominent in her
      right hand. Based on our finding and other previous case reports we conclude that
      metarpals shortening is not a specific finding of PHP-Ia or PPHP and it may be
      found in IPH cases. 

PMID- 24083183
TI  - Local recurrence as a first sign of parathyroid malignancy! Need to redefine the
      criteria for diagnosis of parathyroid carcinoma.
AB  - Pathological criteria alone do not make an accurate diagnosis of parathyroid
      carcinoma in cases of well-defined organ contained lesion without local and
      distant metastasis. Intra-operative appearance of pale, grayish, firm tumor is
      highly suggestive of parathyroid carcinoma, even though this finding is not
      included in the pathological criteria for diagnosing a malignancy. Gross features
      of the tumor also should be added to the pathological criteria so as to ensure an
      accurate assessment of the biological behavior of the parathyroid tumor. 

PMID- 24083184
TI  - Lithium-induced parathyroid dysfunction: A new case.
AB  - Lithium salts are widely used in psychiatric practice and are known to induce
      thyroid dysfunction. Lithium-induced parathyroid dysfunction is rare. We are
      reporting a case of hyperparathyroidism in a 28-year-old female patient who was
      on lithium carbonate for 2 years, when she developed osteopenia and girdle girdle
      type muscle weakness. Biochemical parameters showed hyperparathyroidism with
      shift of calcium creatinine clearance ratio to 0.013, indicating an error in
      threshold of calcium sensing receptor. The patient eventually required
      parathyroidectomy and the histology of the gland showed atypical features. 

PMID- 24083186
TI  - Bilateral adrenal infarction in Crohn's disease.
AB  - Adrenal infarction is an uncommon cause of adrenal insufficiency. We herein
      present unique occurrence of bilateral adrenal infarction detected on imaging in
      a young female with known history of Crohn's disease. The patient responded well
      to steroids and is on follow up. To our knowledge, this is the first case
      reported in English literature of adrenal infarct associated with Crohn's disease
      as extraintestinal manifestation. 

PMID- 24083187
TI  - Malignant thyroglossal duct cyst with synchronous occult thyroid gland papillary
      carcinoma.
AB  - A 52-year-old male was referred to our department with complaints of a painless
      midline neck swelling. Clinico-radiological evaluation suggested a 6 * 5 cm
      thyroglossal cyst with non-palpable nodules in isthmus and right lobe of thyroid
      gland. FNAC of the thyroglossal cyst was suggestive of papillary carcinoma. He
      underwent Sistrunk's operation, total thyroidectomy, and central compartment neck
      dissection. Co-existence of papillary carcinoma of thyroid gland and thyroglossal
      cyst is a rare presentation and in this report, we describe our management and
      propose an evidence-based algorithm to assist decision-making in the management
      of these patients in future. 

PMID- 24083188
TI  - Concurrent parathyroid carcinoma and adenoma: A rare presentation of a rarer
      disease entity.
AB  - Parathyroid carcinoma is a rare disease. But multiglandular parathyroid neoplasm
      is even rarer. A high level of suspicion, on the basis of clinical, hematological
      tests and intraoperative findings is necessary to treat this disease entity,
      particularly in the absence of palpable neck masses. Preoperative localization is
      important. Bilateral neck exploration should be done routinely and all 4 glands
      seen to avoid missing out other pathological glands. 

PMID- 24083189
TI  - Primary hyperparathyroidism in a case of chronic myelogenous leukemia.

PMID- 24083190
TI  - Thyroid disorders in pregnancy: An overview of literature from Pakistan.

PMID- 24083191
TI  - Serum lipids and diabetic retinopathy.

PMID- 24083192
TI  - Diabetes education: "Personal" family member or "impersonal" diabetes educator?

PMID- 24083193
TI  - Newer therapies in the operative management of phaeochromocytoma.

PMID- 24083194
TI  - Raised CA19.9 and hepatic space occupying lesion after teriparatide therapy in a
      case of polyostotic fibrous dysplasia.

PMID- 24083195
TI  - Alstrom syndrome: A rare association of retinitis pigmentosa with insulin
      resistance syndrome.

PMID- 24083196
TI  - Endocrine and diabetes research from SAARC (South Asian Association for Regional
      Cooperation) countries.

PMID- 24083197
TI  - Society of Pharmaceutical Education and ResearchTM official news magazine "SPER
      Times" inaugural issue released.

PMID- 24083198
TI  - Clinical Research in India: The current scenario and prospects.

PMID- 24083199
TI  - Assessment of multifunctional contrast agent probes in neuroimaging: Implications
      of nanopharmaceutical therapeutic interventions.
AB  - Recently, a clear association has been found between the progression of motor
      neurodegenerative disorders (MNDs) and carotid atherosclerosis. Significant
      vascular abnormalities with arterial hypertension were shown to be in patients
      with familial antecedents of MNDs. The main scope of this work is to explore the
      feasibility of recently developed integrated nano-based imaging modalities for
      the assessment of early diagnosis of the inflammatory processes associated with
      the neurological disorder syndromes, with the implication of recently developed
      nanopharmaceutical therapeutic interventions. 

PMID- 24083200
TI  - Informed consent: Issues and challenges.
AB  - Informed consent is an ethical and legal requirement for research involving human
      participants. It is the process where a participant is informed about all aspects
      of the trial, which are important for the participant to make a decision and
      after studying all aspects of the trial the participant voluntarily confirms his
      or her willingness to participate in a particular clinical trial and significance
      of the research for advancement of medical knowledge and social welfare. The
      concept of informed consent is embedded in the principles of Nuremberg Code, The
      Declaration of Helsinki and The Belmont Report. Informed consent is an inevitable
      requirement prior to every research involving human being as subjects for study.
      Obtaining consent involves informing the subject about his or her rights, the
      purpose of the study, procedures to be undertaken, potential risks and benefits
      of participation, expected duration of study, extent of confidentiality of
      personal identification and demographic data, so that the participation of
      subjects in the study is entirely voluntary. This article provides an overview of
      issues in informed consent: The obligations of investigator, sponsor and
      Institutional Review Board to protect rights and welfare of human research
      subjects. It discusses about the basic elements of informed consent and the
      process to be followed while obtaining informed consent. Some of the
      circumstances under which informed consent can be waived and ethical challenges
      faced by physicians in obtaining informed consent from subjects are also
      highlighted in this article. 

PMID- 24083201
TI  - Rheological behavior and stability of ciprofloxacin suspension: Impact of
      structural vehicles and flocculating agent.
AB  - Ciprofloxacin is a fluoroquinolone and is used against a broad spectrum of gram
      negative and gram-positive bacteria. The aim of the study is to investigate the
      effect of structural vehicles and other formulating factors on physical stability
      and rheological behavior of ciprofloxacin suspension. To formulate the
      suspensions, the effect of glycerin and polysorbate 80 as wetting agents was
      evaluated. Then to achieve controlled flocculation, different concentrations of
      sodium chloride and calcium chloride were added. After choosing suitable wetting
      and flocculating agents, structural vehicles such as sodium carboxyl methyl
      cellulose (NaCMC), hydroxypropylmethylcellulose (HPMC) and Veegum were evaluated.
      Physical stability parameters such as sedimentation volume, the degree of
      flocculation and the ease of redispersion of the suspensions and growth of
      crystals were evaluated. After incorporation of structural vehicles, the
      rheological properties of formulations containing were also studied to find out
      their rheological behavior. According to the results, suspension containing
      glycerin (0.2% w/v) and sodium chloride (0.05% w/v) as wetting agent and
      flocculating agent, respectively, were the most stable formulations regarding
      their F and N. Microscopic observations showed the growth of crystals in
      ciprofloxacin suspension in formulation without excipients and the minimum amount
      of crystal growth was seen in suspension containing NaCMC (0.25% w/v), Veegum
      (0.1% w/v) and NaCl (0.05% w/v). Rheological studies showed that almost all of
      the formulations had psuedoplastic behavior with different degree of thixotropy.
      The formulation containing NaCMC (0.25% w/v), Veegum (0.1% w/v) and NaCl (0.05%
      w/v) was the most stable formulation. It may be concluded that by altering the
      amount ratios of formulation factors, the best rheological behavior and the most
      proper thixotropy may be achieved. 

PMID- 24083202
TI  - beta-sitosterol in different parts of Saraca asoca and herbal drug ashokarista:
      Quali-quantitative analysis by liquid chromatography-mass spectrometry.
AB  - beta-sitosterol is an important component in food and herbal products and
      beneficial in hyperlipidemia. Its higher concentrations in serum may lead to
      coronary artery disease in case of sitosterolemia. Therefore, it is essential to
      determine the quantity of beta-sitosterol in food and herbal drugs. Saraca asoca
      and its preparations have been widely used by traditional healers are also a
      source of beta-sitosterol. In the present study, quantitative estimation of beta
      sitosterol present in hot and cold water extracts of bark, regenerated bark,
      leaves and flowers of the S. asoca and Ashokarista drugs were carried out first
      time using high performance liquid chromatography coupled (HPLC) with quadrupole
      time-of-flight mass spectrometry. Different concentrations of beta-sitosterol and
      crude extracts were estimated by HPLC and targeted mass spectrometry. Standard
      curve for beta-sitosterol was prepared from the intensities of transitions
      (397.50 -> 147.0987 m/z) having regression coefficient (r (2)) 0.9952. Out of
      eight extracts and two drugs used in the study bark water, leaves water and
      leaves hot water extracts were found to have a considerable quantity of beta
      sitosterol, i.e. 170, 123.5 and 19.3 ng/mL, respectively. The results showed
      significant differences in the distribution of beta-sitosterol among different
      organs of S. asoca and drugs prepared from its bark. HPLC/electrospray
      ionizationmass spectroscopy method is accurate, reproducible and requires less
      specimen, sample preparation and analysis time over HPLC assay. This type of
      approaches could be helpful for the quality control of herbal medicines and
      provides necessary information for the rational utilization of plant resources. 

PMID- 24083203
TI  - Formulation and optimization of fast dissolving intraoral drug delivery system
      for clobazam using response surface methodology.
AB  - Clobazam is a newer 1,5-benzodiazepine used for the treatment of epilepsy. It is
      better tolerated and less sedating than other benzodiazepines. Absorption of the
      drug can be impacted by oral fast dissolving dosage form; this may have
      implications for epilepsy in pediatrics and those having difficulty in swallowing
      tablets/capsules resulting in improved patient compliance. The purpose of the
      present investigation was to formulate and optimize clobazam oro-dissolving
      tablets by direct compression method using response surface methodology (RSM).
      Oro-dispersible tablets of clobazam were prepared by direct compression method
      using crospovidone (2-6%) as a superdisintegrant, microcrystalline cellulose
      (MCC) (20-40%) was used as diluents along with directly compressible mannitol to
      enhance mouth feel. A 3(2) full factorial design was applied to investigate the
      combined effect of two formulation variables: amount of crospovidone and MCC over
      the independent variables disintegration time, wetting time and percent drug
      release. Disintegration time showed by all formulations was found to be in the
      range of 24.3-193 s based on evaluation parameters the formulation containing 6%
      of crospovidone and 30% of MCC showed promising performance against all other
      formulations. The results demonstrated that the RSM could efficiently be applied
      for the formulation of clobazam oro-dispersible tablets; therefore, constitute an
      advance in the management of epileptic attacks. 

PMID- 24083204
TI  - Method development for Lawsone estimation in Trichup herbal hair powder by high
      performance thin layer chromatography.
AB  - A simple, specific, accurate, precise and robust high-performance thin-layer
      chromatographic method has been developed and validated for estimation of Lawsone
      in Trichup herbal hair powder (coded as a THHP), polyherbal formulation. The
      chromatographic development was carried out on aluminum plates pre-coated with
      silica gel 60F254 and good resolution was achieved with Toluene: Ethyl acetate:
      Glacial acetic acid (8:1:1 v/v/v) as mobile phase. Lawsone detection was carried
      out densitometrically at 277 nm and obtained retardation factor value was 0.46 +/
      0.02. The method was validated with respect to specificity, linearity, accuracy,
      precision and robustness. The calibration curve was achieved to be linear over a
      range of 5-60 MUg/ml and regression coefficient was obtained 0.998. Accuracy of
      chromatographic method was evaluated by standard addition method; recovery was
      obtained 99.25 +/- 0.61%. The peak purity of Lawsone was achieved 0.999 r.
      Relative standard deviation for intraday and inter-day precision was 0.37-0.56%
      and 0.42-0.55%, respectively. The limit of detection and limit of quantification
      of the Lawsone were found to be 1.08 MUg/m land 3.28 MUg/ml, respectively. This
      result shows that the method was well validated. In the present study, the
      Lawsone content was found 0.322 +/- 0.014% in THHP. This study reveals that the
      proposed high performance thin layer chromatography method is accurate, fast and
      cost- effective for routine estimation of Lawsone in polyherbal formulation. 

PMID- 24083205
TI  - A comparative study of efficacy of atorvastatin alone and its combination with
      fenofibrate on lipid profile in type 2 diabetes mellitus patients with
      hyperlipidemia.
AB  - Mixed dyslipidemia is characterized by increased low-density lipoprotein
      cholesterol (LDL-C) elevated triglycerides (TGs) and decrease high-density
      lipoprotein cholesterol (HDL-C). It is more common in diabetes and is associated
      with an increased risk of coronary artery disease. Monotherapy with statins or
      fibrates may not effectively control all lipid parameters. The atorvastatin
      fenofibrate combination has been shown to have highly beneficial effect on lipid
      parameters in type 2 diabetes associated with combined hyperlipidemia (CHL). In
      an open-label study, we evaluated the efficacy of atorvastatin alone and in
      combination with fenofibrate in 60 types 2 diabetes mellitus patients associated
      with hyperlipidemia. Patients were randomly assigned to receive atorvastatin 10
      mg (Group 1) or combination of atorvastatin 10 mg and fenofibrate 145 mg (Group
      2) once daily for 12 weeks. The effect of drugs on lipid profile was evaluated
      before and after treatment. After 12 weeks, the reduction in total cholesterol
      (TC), TGs, LDL-C, VLDL-C was 28%, 20%, 37% and 20% in Group 1 (P < 0.001 for all)
      as compared with 31%, 39%, 33% and 40% in Group 2 (P < 0.001 for all). There was
      insignificant rise in HDL-C in Group 1 (P = 0.71) and insignificant decrease in
      HDL-C (P = 0.70) in Group 2. During the combination therapy, the decrease in TC,
      TGs and VLDL-C was greater than atorvastatin alone. The combination of
      atorvastatin with fenofibrate in type 2 diabetes patients with CHL may have a
      favorable effect on some major coronary artery disease risk factors. 

PMID- 24083206
TI  - Radiographic evaluation of the symphysis menti as a donor site for an autologous
      bone graft in pre-implant surgery.
AB  - PURPOSE: This study was performed to obtain a quantitative evaluation of the
      cortical and cancellous bone graft harvestable from the mental and canine
      regions, and to evaluate the cortical vestibular thickness. MATERIALS AND
      METHODS: This study collected cone-beam computed tomographic (CBCT) images of 100
      Italian patients. The limits of the mental region were established: 5 mm in front
      of the medial margin of each mental foramen, 5 mm under the apex of each tooth
      present, and above the inferior mandibular cortex. Cortical and cancellous bone
      volumes were evaluated using SimPlant software (SimPlant 3-D Pro, Materialize,
      Leuven, Belgium) tools. In addition, the cortical vestibular thickness (minimal
      and maximal values) was evaluated in 3 cross-sections corresponding to the right
      canine tooth (3R), the median section (M), and the left canine tooth (3L).
      RESULTS: The cortical volume was 0.71+/-0.23 mL (0.27-1.96 mL) and the cancellous
      volume was 2.16+/-0.76 mL (0.86-6.28 mL). The minimal cortical vestibular
      thickness was 1.54+/-0.41 mm (0.61-3.25 mm), and the maximal cortical vestibular
      thickness was 3.14+/-0.75mm(1.01-5.83 mm). CONCLUSION: The use of the imaging
      software allowed a patient-specific assessment of mental and canine region bone
      availability. The proposed evaluation method might help the surgeon in the
      selection of the donor site by the comparison between bone availability in the
      donor site and the reconstructive exigency of the recipient site.

PMID- 24083207
TI  - Radiopacity of restorative composites by conventional radiograph and digital
      images with different resolutions.
AB  - PURPOSE: This study was performed to evaluate and compare the radiopacity of
      dentin, enamel, and 8 restorative composites on conventional radiograph and
      digital images with different resolutions. MATERIALS AND METHODS: Specimens were
      fabricated from 8 materials and human molars were longitudinally sectioned 1.0 mm
      thick to include both enamel and dentin. The specimens and tooth sections were
      imaged by conventional radiograph using #4 sized intraoral film and digital
      images were taken in high speed and high resolution modes using a phosphor
      storage plate. Densitometric evaluation of the enamel, dentin, restorative
      materials, a lead sheet, and an aluminum step wedge was performed on the
      radiographic images. For the evaluation, the Al equivalent (mm) for each material
      was calculated. The data were analyzed using one-way ANOVA and Tukey's test
      (p<0.05), considering the material factor and then the radiographic method
      factor, individually. RESULTS: The high speed mode allowed the highest
      radiopacity, while the high resolution mode generated the lowest values.
      Furthermore, the high resolution mode was the most efficient method for
      radiographic differentiation between restorative composites and dentin. The
      conventional radiograph was the most effective in enabling differentiation
      between enamel and composites. The high speed mode was the least effective in
      enabling radiographic differentiation between the dental tissues and restorative
      composites. CONCLUSION: The high speed mode of digital imaging was not effective
      for differentiation between enamel and composites. This made it less effective
      than the high resolution mode and conventional radiographs. All of the composites
      evaluated showed radiopacity values that fit the ISO 4049 recommendations.

PMID- 24083208
TI  - The combination of a histogram-based clustering algorithm and support vector
      machine for the diagnosis of osteoporosis.
AB  - PURPOSE: To prevent low bone mineral density (BMD), that is, osteoporosis, in
      postmenopausal women, it is essential to diagnose osteoporosis more precisely.
      This study presented an automatic approach utilizing a histogram-based automatic
      clustering (HAC) algorithm with a support vector machine (SVM) to analyse dental
      panoramic radiographs (DPRs) and thus improve diagnostic accuracy by identifying
      postmenopausal women with low BMD or osteoporosis. MATERIALS AND METHODS: We
      integrated our newly-proposed histogram-based automatic clustering (HAC)
      algorithm with our previously-designed computer-aided diagnosis system. The
      extracted moment-based features (mean, variance, skewness, and kurtosis) of the
      mandibular cortical width for the radial basis function (RBF) SVM classifier were
      employed. We also compared the diagnostic efficacy of the SVM model with the back
      propagation (BP) neural network model. In this study, DPRs and BMD measurements
      of 100 postmenopausal women patients (aged >50 years), with no previous record of
      osteoporosis, were randomly selected for inclusion. RESULTS: The accuracy,
      sensitivity, and specificity of the BMD measurements using our HAC-SVM model to
      identify women with low BMD were 93.0% (88.0%-98.0%), 95.8% (91.9%-99.7%) and
      86.6% (79.9%-93.3%), respectively, at the lumbar spine; and 89.0% (82.9%-95.1%),
      96.0% (92.2%-99.8%) and 84.0% (76.8%-91.2%), respectively, at the femoral neck.
      CONCLUSION: Our experimental results predict that the proposed HAC-SVM model
      combination applied on DPRs could be useful to assist dentists in early diagnosis
      and help to reduce the morbidity and mortality associated with low BMD and
      osteoporosis.

PMID- 24083209
TI  - Bilateral and pseudobilateral tonsilloliths: Three dimensional imaging with cone
      beam computed tomography.
AB  - PURPOSE: Tonsilloliths are calcifications found in the crypts of the palatal
      tonsils and can be detected on routine panoramic examinations. This study was
      performed to highlight the benefits of cone-beam computed tomography (CBCT) in
      the diagnosis of tonsilloliths appearing bilaterally on panoramic radiographs.
      MATERIALS AND METHODS: The sample group consisted of 7 patients who had bilateral
      radiopaque lesions at the area of the ascending ramus on panoramic radiographs.
      CBCT images for every patient were obtained from both sides of the jaw to
      determine the exact locations of the lesions and to rule out other
      calcifications. The calcifications were evaluated on the CBCT images using
      Ez3D2009 software. Additionally, the obtained images in DICOM format were
      transferred to ITK SNAP 2.4.0 pc software for semiautomatic segmentation.
      Segmentation was performed using contrast differences between the soft tissues
      and calcifications on grayscale images, and the volume in mm(3) of the segmented
      three dimensional models were obtained. RESULTS: CBCT scans revealed that what
      appeared on panoramic radiographs as bilateral images were in fact unilateral
      lesions in 2 cases. The total volume of the calcifications ranged from 7.92 to
      302.5mm(3). The patients with bilaterally multiple and large calcifications were
      found to be symptomatic. CONCLUSION: The cases provided the evidence that
      tonsilloliths should be considered in the differential diagnosis of radiopaque
      masses involving the mandibular ramus, and they highlight the need for a CBCT
      scan to differentiate pseudo- or ghost images from true bilateral pathologies.

PMID- 24083210
TI  - Comparison of high-resolution and standard zoom imaging modes in cone beam
      computed tomography for detection of longitudinal root fracture: An in vitro
      study.
AB  - PURPOSE: The purpose of this study was to compare the efficacy of two imaging
      modes in a cone beam computed tomography (CBCT) system in detecting root fracture
      in endodontically-treated teeth with fiber posts or screw posts by selecting two
      fields of view. MATERIALS AND METHODS: In this study, 78 endodontically-treated
      single canal premolars were included. A post space was created in all of them.
      Then the teeth were randomly set in one of 6 artificial dental arches. In 39 of
      the 78 teeth set in the 6 dental arches, a root fracture was intentionally
      created. Next, a fiber post and a screw post were cemented into 26 teeth having
      equal the root fractures. High resolution (HiRes) and standard zoom images were
      provided by a CBCT device. Upon considering the reconstructed images, two
      observers in agreement with each other confirmed the presence or absence of root
      fracture. A McNemar test was used for comparing the results of the two modes.
      RESULTS: The frequency of making a correct diagnosis using the HiRes zoom imaging
      mode was 71.8% and in standard zoom was 59%. The overall sensitivity and
      specificity in diagnosing root fracture in the HiRes mode were 71.79% and 46.15%
      and in the standard zoom modes were 58.97% and 33.33%, respectively. CONCLUSION:
      There were no significant differences between the diagnostic values of the two
      imaging modes used in the diagnosis of root fracture or in the presence of root
      canal restorations. In both modes, the most true-positive results were reported
      in the post space group.

PMID- 24083212
TI  - Effect of digital noise reduction on the accuracy of endodontic file length
      determination.
AB  - PURPOSE: The aim of the present study was to evaluate the measurement accuracy of
      endodontic file length on periapical digital radiography after application of
      noise reduction digital enhancement. MATERIALS AND METHODS: Thirty-five human
      single-rooted permanent teeth with canals measuring 20-24 mm in length were
      selected. ISO #08 endodontic files were placed in the root canals of the teeth.
      The file lengths were measured with a digital caliper as the standard value.
      Standard periapical digital images were obtained using the Digora digital
      radiographic system and a dental X-ray unit. In order to produce the enhanced
      images, the noise reduction option was applied. Two blinded radiologists measured
      the file lengths on the original and enhanced images. The measurements were
      compared by repeated measures ANOVA and the Bonferroni test (alpha=0.05).
      RESULTS: Both the original and enhanced digital images provided significantly
      longer measurements compared with the standard value (P<0.05). There were no
      significant differences between the measurement accuracy of the original and
      enhanced images (P>0.05). CONCLUSION: Noise reduction digital enhancement did not
      influence the measurement accuracy of the length of the thin endodontic files on
      the digital periapical radiographs despite the fact that noise reduction could
      result in the elimination of fine details of the images.

PMID- 24083211
TI  - Attitude of the Korean dentists towards radiation safety and selection criteria.
AB  - PURPOSE: X-ray exposure should be clinically justified and each exposure should
      be expected to give patients benefits. Since dental radiographic examination is
      one of the most frequent radiological procedures, radiation hazard becomes an
      important public health concern. The purpose of this study was to investigate the
      attitude of Korean dentists about radiation safety and use of criteria for
      selecting the frequency and type of radiographic examinations. MATERIALS AND
      METHODS: The study included 267 Korean dentists. Five questions related to
      radiation safety were asked of each of them. These questions were about factors
      associated with radiation protection of patients and operators including the use
      of radiographic selection criteria for intraoral radiographic procedures.
      RESULTS: The frequency of prescription of routine radiographic examination (an
      example is a panoramic radiograph for screening process for occult disease) was
      34.1%, while that of selective radiography was 64.0%. Dentists' discussion of
      radiation risk and benefit with patients was infrequent. More than half of the
      operators held the image receptor by themselves during intraoral radiographic
      examinations. Lead apron/thyroid collars for patient protection were used by
      fewer than 22% of dental offices. Rectangular collimation was utilized by fewer
      than 15% of dental offices. CONCLUSION: The majority of Korean dentists in the
      study did not practice radiation protection procedures which would be required to
      minimize exposure to unnecessary radiation for patients and dental professionals.
      Mandatory continuing professional education in radiation safety and development
      of Korean radiographic selection criteria is recommended.

PMID- 24083213
TI  - Evaluation of the accuracy of linear and angular measurements on panoramic
      radiographs taken at different positions.
AB  - PURPOSE: This study assessed the accuracy of linear and angular measurements on
      panoramic radiographs taken at different positions in vitro. MATERIALS AND
      METHODS: Two acrylic models were fabricated from a cast with normal occlusion.
      Straight and 75 degrees  mesially and lingually angulated pins were placed, and
      standardized panoramic radiographs were taken at standard position, at an 8
      degrees  downward tilt of the occlusal plane compared to the standard position,
      at an 8 degrees  upward tilt of the anterior occlusal plane, and at a 10 degrees 
      downward tilt of the right and left sides of the model. On the radiographs, the
      length of the pins above (crown) and below (root) the occlusal plane, total pin
      length, crown-to-root ratio, and angulation of pins relative to the occlusal
      plane were calculated. The data were subjected to repeated measures ANOVA and LSD
      multiple comparisons tests. RESULTS: Significant differences were noted between
      the radiographic measurements and true values in different positions on both
      models with linear (P<0.001) and those with angulated pins (P<0.005). No
      statistically significant differences were observed between the angular
      measurements and baselines of the natural head posture at different positions for
      the linear and angulated pins. CONCLUSION: Angular measurements on panoramic
      radiographs were sufficiently accurate and changes in the position of the
      occlusal plane equal to or less than 10 degrees  had no significant effect on
      them. Some variations could exist in the pin positioning (head positioning), and
      they were tolerable while taking panoramic radiographs. Linear measurements
      showed the least errors in the standard position and 8 degrees  upward tilt of
      the anterior part of the occlusal plane compared to other positions.

PMID- 24083214
TI  - Florid osseous dysplasia in a middle-aged Turkish woman: A case report.
AB  - Florid osseous dysplasia (FOD) is an uncommon, benign, cemento-osseous lesion of
      the jaws. The etiology of FOD is still unknown. It is often asymptomatic and may
      be identified on routine dental radiographs. The classic radiographic appearance
      of FOD is amorphous, lobulated, mixed radiolucent/radiopaque masses of cotton
      wool appearance with a sclerotic border in the jaws. In our case the lesion was
      found incidentally on routine periapical radiographs taken for restored teeth and
      edentulous areas. For further and detailed examination, a panoramic radiograph
      and cone-beam computed tomograph (CBCT) were taken. The panoramic radiograph and
      CBCT revealed maxillary bilateral and symmetrical, non-expansile, well-defined,
      round, radiopaque masses in contact with the root of the maxillary right second
      molar and left first molar teeth. Our aim in presenting this case report was to
      highlight the importance of imaging in diagnosis of FOD. 

PMID- 24083215
TI  - A repeatedly recurrent desmoplastic ameloblastoma after removal and allobone
      graft: Radiographic features compared with histological changes.
AB  - A 40-year-old man suffered from a repeatedly recurrent desmoplastic ameloblastoma
      in the right maxillary anterior and premolar regions. During the first visit, the
      patient was provisionally histopathologically diagnosed with a developmental
      cyst, and it was confirmed to be unicystic ameloblastoma and resected. Four years
      later, the lesion recurred, and was diagnosed as a desmoplastic type of
      ameloblastoma and removed again. Then, 5 years after the second surgery, the
      lesion recurred again, and was diagnosed as a type containing a follicular
      pattern, recurrent ameloblastoma. A panoramic radiograph showed a multilocular
      and mixed radiolucent/radiopaque expansile lesion at the first visit, a
      unilocular cystic lesion confined to the premolar area at the second visit, and a
      small soap bubble appearance in the molar area in the final visit. Cone-beam
      computed tomographic images of the final recurrence of the tumor revealed
      multiple small cyst-like structures in the right maxillary anterior and posterior
      regions. 

PMID- 24083216
TI  - A rare case of dilated invaginated odontome with talon cusp in a permanent
      maxillary central incisor diagnosed by cone beam computed tomography.
AB  - It has been a challenge to establish the accurate diagnosis of developmental
      tooth anomalies based on periapical radiographs. Recently, three-dimensional
      imaging by cone beam computed tomography has provided useful information to
      investigate the complex anatomy of and establish the proper management for tooth
      anomalies. The most severe variant of dens invaginatus, known as dilated
      odontome, is a rare occurrence, and the cone beam computed tomographic findings
      of this anomaly have never been reported for an erupted permanent maxillary
      central incisor. The occurrence of talon cusp occurring along with dens
      invaginatus is also unusual. The aim of this report was to show the importance of
      cone beam computed tomography in contributing to the accurate diagnosis and
      evaluation of the complex anatomy of this rare anomaly. 

PMID- 24083217
TI  - CBCT findings of periapical cemento-osseous dysplasia: A case report.
AB  - Periapical cemento-osseous dysplasia (PCOD) is a subtype of cemento-osseous
      dysplasia that usually occurs in middle-aged black women. This report described a
      case of a 45-year-old Iranian woman who was diagnosed with PCOD on the basis of
      cone beam computed tomographic (CBCT) findings. CBCT enabled detailed
      visualization of the bone changes. This report described the special radiographic
      characteristics of PCOD, including discontinuity of the lingual cortex on the
      CBCT sectional and three-dimensional images. 

PMID- 24083218
TI  - The emerging role of outdoor and indoor air pollution in cardiovascular disease.
AB  - Outdoor and indoor air pollution poses a significant cardiovascular risk, and has
      been associated with atherosclerosis, the main underlying pathology in many
      cardiovascular diseases. Although, it is well known that exposure to air
      pollution causes pulmonary disease, recent studies have shown that cardiovascular
      health consequences of air pollution generally equal or exceed those due to
      pulmonary diseases. The objective of this article is to evaluate the current
      evidence on the emerging role of environmental air pollutions in cardiovascular
      disease, with specific focus on the types of air pollutants and mechanisms of air
      pollution-induced cardiotoxicity. Published literature on pollution was
      systematically reviewed and cited in this article. It is hoped that this review
      will provide a better understanding of the harmful cardiovascular effects induced
      by air pollution exposure. This will help to bring a better understanding on the
      possible preventive health measures and will also serve regulatory agencies and
      researchers. In addition, elucidating the biological mechanisms underlying the
      link between air pollution and cardiovascular disease is an essential target in
      developing novel pharmacological strategies aimed at decreasing adverse effects
      of air pollution on cardiovascular system. 

PMID- 24083219
TI  - Cardiovascular repercussions of the pseudoexfoliation syndrome.
AB  - Pseudoexfoliation syndrome is a primarily ophthalmological disorder caused by
      deposition of whitish-gray protein on the lens, iris, and multiple other eye
      tissues. There is increasing evidence over the previous years that
      pseudoexfoliation syndrome is a systemic disorder with various extraocular
      manifestations and has recently been linked to several cardiovascular disorders.
      The present article aims to summarize the current knowledge on cardiovascular
      implications of this well-described clinical entity. 

PMID- 24083220
TI  - Spontaneous pneumomediastinum: time for consensus.
AB  - Pneumomediastinum (PM) is defined as the presence of free air in the mediastinal
      cavity. It is often regarded as a revealing sign of a more serious medical
      condition. PM is broken down into two categories, one, with an instigating event,
      referred to as secondary PM. The other is when free air is discovered in the
      mediastinal cavity without a clear etiology, referred to as spontaneous
      pneumomediastinum (SPM). Often misdiagnosed due to the vague nature of presenting
      symptoms, SPM must be part of the differential diagnosis of a chest pain patient
      to expedite discovery and if necessary, management. A MedLine/PubMED search was
      performed identifying all relevant articles with "SPM" in the title. Six case
      series were reviewed to determine what clinical scenario constitutes a possible
      case of SPM. Results showed that almost all patients with SPM exhibited some
      chest pain, but Hamman's crunch was present in only one-fifth of patients.
      Patients with certain pre-existing pulmonary diseases showed a greater propensity
      for the presence of free air in the mediastinal cavity. SPM must be diagnosed and
      managed promptly due to rare, but serious complications and any chest pain with
      an unknown etiology should contain SPM in the differential diagnosis. 

PMID- 24083221
TI  - Treatment of allergic rhinitis with probiotics: an alternative approach.
AB  - Allergic rhinitis is a skewed immune reaction to common antigens in the nasal
      mucosa; current therapy is not satisfactory and can cause a variety of
      complications. In recent decades, the incidence of allergic rhinitis is
      increasing every year. Published studies indicate that probiotics are beneficial
      in treating allergic rhinitis. This review aims to help in understanding the role
      of probiotics in the treatment of allergic rhinitis. We referred to the PubMed
      database as data source. This review focuses on the following aspects: The types
      of probiotics using in the treatment of allergic rhinitis, approaches of
      administration, its safety, mechanisms of action, treating results, and the
      perspectives to improve effectiveness of probiotics in the treatment of allergic
      rhinitis. This review reports the recent findings regarding the role of
      probiotics in the treatment of allergic rhinitis. Probiotics are a useful
      therapeutic remedy in the treatment of allergic rhinitis, but its underlying
      mechanisms remain to be further investigated. 

PMID- 24083222
TI  - Perspectives of medical interns regarding female feticide and declining sex ratio
      in India.
AB  - BACKGROUND: Female feticide, skewed sex ratio, and its attendant social evils
      have grave ethical undertones for medical professionals and our commitment to
      save lives. A concerted effort by all is essential against female feticide. AIM:
      This study was to assess the knowledge of female feticide, declining sex ratio,
      and corrective measures among medical interns. MATERIALS AND METHODS: A cross
      sectional study was conducted among 79 medical interns. Data werecollected with
      the help of predesigned structured questionnaire. Chi-square tests, Kruskal
      Wallis tests, and Z tests were used to test the significance level. RESULTS:
      Knowledge of current sex ratio was significantly better among female interns than
      male interns. Majority of interns opined that creating awareness is an effective
      measure to combat declining sex ratio and only 33 interns had correct knowledge
      regarding all measures. Only 37.9% of interns knew all the legal indications for
      use of prenatal diagnostic techniques. However, 81% of interns were aware of
      punishments mentioned for violation of the Act. Mean score of knowledge was 22.06
      among males and 24.4 among females. CONCLUSION: The findings in our study
      underline the need to sensitize doctors regardingevery aspect of Pre-Conception
      and Prenatal Diagnostic Techniques Act and selective sex determination.

PMID- 24083223
TI  - Manual khalifa therapy in patients with completely ruptured anterior cruciate
      ligament in the knee: first preliminary results from thermal imaging.
AB  - BACKGROUND: This preliminary publication describes acute temperature effects
      after manual Khalifa therapy. AIMS: The goal of this study was to describe
      temperature distribution and the effects on surface temperature of the knees and
      feet in patients with completely ruptured anterior cruciate ligament before and
      immediately after the manual therapy. MATERIALS AND METHODS: Ten male patients
      were investigated with thermal imaging. An infrared camera operating at a
      wavelength range of 7.5-13 MUm was used. Temperature was analyzed at three
      locations on both knees and in addition on both feet. RESULTS: The study revealed
      that baseline temperature of the injured knee differed from that of the untreated
      control knee. After the therapy on the injured knee, the surface temperature was
      significantly increased on both knees (injured and control). There were no
      significant changes in the temperature of the feet. CONCLUSIONS: Further studies
      using continuous thermal image recording may help to explain the details
      concerning the temperature distribution.

PMID- 24083224
TI  - Profile of hepatic involvement by dengue virus in dengue infected children.
AB  - BACKGROUND: The spectrum of liver dysfunction in children with dengue infection
      is wide and has been associated with disease severity. AIMS: This study was
      undertaken to estimate the range of hepatic involvement in dengue infection in
      children. MATERIALS AND METHODS: This study assessed the biochemical and clinical
      profile of hepatic involvement by dengue virus in 120 children with serologically
      positive dengue fever (DF), aged 2 months to 14 years. RESULTS: All cases were
      grouped into DF without warning signs (Group 1), DF with warning signs (Group 2)
      and severe dengue (Group 3) according to revised World Health Organization 2009
      criteria. The spectrum of hepatic manifestations included hepatomegaly (80.8%),
      hepatic tenderness (46.3%), jaundice (60%), raised aspartate transaminase (AST),
      alanine transaminase (ALT) and prolonged prothrombin time (41.7%) and reduced
      serum albumin (56%). CONCLUSIONS: Hepatic dysfunction was observed more in Groups
      2 and 3. There was 84.4% and 93.75% ALT and AST elevation respectively in Group 2
      and 94.5% and 95.9% ALT and AST elevation respectively in Group 3 and fulminant
      hepatic failure was observed in Group 3. Therefore in a child with fever,
      jaundice, hepatomegaly and altered liver function tests, the diagnosis of dengue
      infection should be strongly considered in areas where dengue infection is
      endemic.

PMID- 24083225
TI  - Cryptococcal meningoencephalitis in human immunodeficiency virus/acquired
      immunodeficiency syndrome in douala, cameroon: a cross sectional study.
AB  - BACKGROUND: Cryptococcal meningoencephalitis (CM) kills about half a million
      human immunodeficiency virus (HIV) patients per year, mostly in Africa. AIM: The
      aim of this study was to determine the prevalence, clinical presentation and in
      hospital outcome of CM among HIV-infected patients in Douala. MATERIALS AND
      METHODS: A cross-sectional clinical note review of 672 HIV-1 patients' files
      admitted from January 1 (st) 2004 to December 31 (st) 2009 at the Internal
      Medicine unit of the Douala General Hospital, Cameroon was performed. Only
      patients diagnosed of CM by microscopy of Indian ink stained cerebrospinal fluid
      (CSF) were studied. RESULTS: The prevalence of CM in the study was 11.2%. Mean
      age of patients was 36.9 ? 12.7 years. Median cluster of differentiation 4 (CD4)
      cell count was 23 cells/MUL, (interquartile range [IQR]: 10-61) and 62.7% of CD4
      cell counts were >50 cells/MUL. The most prevalent symptom was headache in 97.3%
      of patients. In CSF, median proteins was 0.9 g/L (IQR: 0.6-1); median glucose 0.2
      g/L (IQR: 0.1-0.3) and median leucocyte count 54 cells/MUL (IQR: 34-76) mostly of
      mixed cellularity. The case fatality rate was 52% and low CD4 cell count was
      strongly associated with death, odd ratio 4.6 (95% confidence interval: 2.6-8.0,
      P > 0.001). CONCLUSION: The high case fatality of CM in Douala warrants adequate
      diagnostic measures and optimization of standardized treatment to reduce
      mortality.

PMID- 24083226
TI  - Central nervous system and Cryptococcus neoformans.

PMID- 24083227
TI  - Severe vitamin d deficiency, myopathy, and rhabdomyolysis.

PMID- 24083228
TI  - Diagnosis of persistent left superior vena cava draining directly into the left
      atrium.

PMID- 24083229
TI  - Limitations of 24-hour Recall Method: Micronutrient Intake and the Presence of
      the Metabolic Syndrome.

PMID- 24083230
TI  - Different mechanisms of inflammation induced in virus and autoimmune-mediated
      models of multiple sclerosis in C57BL6 mice.
AB  - Multiple sclerosis (MS) is an inflammatory demyelinating disease of the human
      central nervous system (CNS). Neurotropic demyelinating strain of MHV (MHV-A59 or
      its isogenic recombinant strain RSA59) induces MS-like disease in mice mediated
      by microglia, along with a small population of T cells. The mechanism of
      demyelination is at least in part due to microglia-mediated myelin stripping,
      with some direct axonal injury. Immunization with myelin oligodendrocyte
      glycoprotein (MOG) induces experimental autoimmune encephalomyelitis (EAE), a
      mainly CD4(+) T-cell-mediated disease, although CD8(+) T cells may play a
      significant role in demyelination. It is possible that both autoimmune and
      nonimmune mechanisms such as direct viral toxicity may induce MS. Our study
      directly compares CNS pathology in autoimmune and viral-induced MS models. Mice
      with viral-induced and EAE demyelinating diseases demonstrated similar patterns
      and distributions of demyelination that accumulated over the course of the
      disease. However, significant differences in acute inflammation were noted.
      Inflammation was restricted mainly to white matter at all times in EAE, whereas
      inflammation initially largely involved gray matter in acute MHV-induced disease
      and then is subsequently localized only in white matter in the chronic disease
      phase. The presence of dual mechanisms of demyelination may be responsible for
      the failure of immunosuppression to promote long-term remission in many MS
      patients. 

PMID- 24083231
TI  - Strength and body composition changes in recreationally strength-trained
      individuals: comparison of one versus three sets resistance-training programmes.
AB  - PURPOSE: The purpose of this study was to determine the effects of increasing the
      volume of weight-training from one to three sets upon body composition and
      muscular strength. METHODS: Sixteen male weight-trainers volunteered to act as
      subjects and were randomly assigned to one of two training groups. Supervised
      weight-training targeting the upper body was conducted three times per week for
      eight weeks using one set (n = 8) or three sets (n = 8) of six repetitions to
      fatigue. Subjects were measured before and after the training intervention for
      (1) strength performance (N and kg) and (2) adiposity (sum of seven skinfold
      thicknesses in mm). RESULTS: Both training groups improved significantly (20.7%)
      in terms of muscular strength (P < 0.05) with no differences being observed
      between the one set (21.98% increase) and three set group (20.71% increase) after
      the training interventions (P > 0.05). Significant decreases were also observed
      for skinfold measures in the one set group (P < 0.05). CONCLUSIONS: One set of
      high intensity resistance training was as effective as three sets for increasing
      the strength of muscle groups in the upper body. The one set protocol also
      produced significantly greater decreases in adiposity.

PMID- 24083233
TI  - Green synthesis of silver nanoparticles using Pinus eldarica bark extract.
AB  - Recently, development of reliable experimental protocols for synthesis of metal
      nanoparticles with desired morphologies and sizes has become a major focus of
      researchers. Green synthesis of metal nanoparticles using organisms has emerged
      as a nontoxic and ecofriendly method for synthesis of metal nanoparticles. The
      objectives of this study were production of silver nanoparticles using Pinus
      eldarica bark extract and optimization of the biosynthesis process. The effects
      of quantity of extract, substrate concentration, temperature, and pH on the
      formation of silver nanoparticles are studied. TEM images showed that
      biosynthesized silver nanoparticles (approximately in the range of 10-40 nm) were
      predominantly spherical in shape. The preparation of nano-structured silver
      particles using P. eldarica bark extract provides an environmentally friendly
      option, as compared to currently available chemical and/or physical methods.

PMID- 24083232
TI  - Anti-actin IgA antibodies identify celiac disease patients with a Marsh 3
      intestinal damage among subjects with moderate anti-TG2 levels.
AB  - A new diagnostic tool (algorithm-1) for coeliac disease (CD) permitting the
      diagnosis without performing the duodenal biopsy has been recently proposed by
      the European Society for Paediatric Gastroenterology, Hepatology, and Nutrition
      (ESPGHAN). It combines symptoms associated with CD, high anti-transglutaminase
      type 2 antibody (anti-TG2) levels, anti-endomysium-IgA antibodies (EMA), and at
      risk HLA. Our aims were (i) to evaluate retrospectively in 227 individuals (149
      CD patients and 78 controls) the algorithm-1, (ii) to reduce the number of
      duodenal biopsies among CD patients for whom algorithm-1 is not applicable
      through the addition of antiactin IgA antibodies (AAA-IgA), and (iii) to evaluate
      prospectively algorithm-1 and AAA-IgA in 50 patients with suspected CD. Algorithm
      1 identified 70 out of 149 CD patients with Marsh 3 lesions. Adding AAA-IgA to
      the remaining patients with anti-TG2 levels comprised between 4 and 10 times
      upper limit of normal (ULN) allowed the detection of further 20 patients with a
      Marsh 3 damage. In our prospective study, algorithm-1 identified 23 out of 50
      patients, whilst further 7 were recognized adding AAA-IgA. We confirm that
      algorithm-1 may avoid the duodenal biopsy in many CD patients and underscores the
      usefulness of AAA-IgA in reducing the number of duodenal biopsies in patients
      with moderate anti-TG2 levels. 

PMID- 24083234
TI  - Who receives home-based perinatal palliative care: experience from Poland.
AB  - CONTEXT: The current literature suggests that perinatal palliative care (PPC)
      programs should be comprehensive, initiated early, and integrative. So far there
      have been very few publications on the subject of home-based PC of newborns and
      neonates. Most publications focus on hospital-based care, mainly in the neonatal
      intensive care units. OBJECTIVE: To describe the neonates and infants who
      received home-based palliative care in Lodz Region between 2005 and 2011.
      METHODS: A retrospective review of medical records. RESULTS: 53 neonates and
      infants were admitted to a home hospice in Lodz Region between 2005 and 2011. In
      general, they are a growing group of patients referred to palliative care.
      Congenital diseases (41%) were the primary diagnoses; out of 53 patients 16 died,
      20 were discharged home, and 17 stayed under hospice care until 2011. The most
      common cause of death (56%) was cardiac insufficiency. Neurological symptoms
      (72%) and dysphagia (58%) were the most common clinical problems. The majority of
      children (45%) had a feeding tube inserted and were oxygen dependent (45%); 39
      families received psychological care and 31 social supports. CONCLUSIONS: For
      terminally ill neonates and infants, perinatal palliative care is an option which
      improves the quality of their lives and provides the family with an opportunity
      to say goodbye.

PMID- 24083235
TI  - Formulation development and stability studies of norfloxacin extended-release
      matrix tablets.
AB  - The aim of this research was to develop a new hydrophilic matrix system
      containing norfloxacin (NFX). Extended-release tablets are usually intended for
      once-a-day administration with benefits to the patient and lower discontinuation
      of the therapy. Formulations were developed with hydroxypropylmethylcellulose or
      poly(ethylene oxide) as hydrophilic polymers, with different molecular weights
      (MWs) and concentrations (20 and 30%). The tablets were found to be stable (6
      months at 40 +/- 2 degrees C and 75 +/- 5% relative humidity), and the film
      coating process is recommended to avoid NFX photodegradation. The dissolution
      profiles demonstrated an extended-release of NFX for all developed formulations.
      Dissolution curves analyzed using the Korsmeyer exponential equation showed that
      drug release was controlled by both drug diffusion and polymer relaxation or
      erosion mechanisms. A more erosion controlled system was obtained for the
      formulations containing lower MW and amount of polymer. With the increase in both
      MW and amount of polymer in the formulation, the gel layer became stronger, and
      the dissolution was more drug-diffusion dependent. Formulations containing
      intermediate MW polymers or high concentration (30%) of low MW polymers
      demonstrated a combination of extended and complete in vitro drug release. This
      way, these formulations could provide an increased bioavailability in vivo. 

PMID- 24083236
TI  - Copper enhanced monooxygenase activity and FT-IR spectroscopic characterisation
      of biotransformation products in trichloroethylene degrading bacterium:
      Stenotrophomonas maltophilia PM102.
AB  - Stenotrophomonas maltophilia PM102 (NCBI GenBank Acc. no. JQ797560) is capable of
      growth on trichloroethylene as the sole carbon source. In this paper, we report
      the purification and characterisation of oxygenase present in the PM102 isolate.
      Enzyme activity was found to be induced 10.3-fold in presence of 0.7 mM copper
      with a further increment to 14.96-fold in presence of 0.05 mM NADH. Optimum
      temperature for oxygenase activity was recorded at 36 degrees C. The reported
      enzyme was found to have enhanced activity at pH 5 and pH 8, indicating presence
      of two isoforms. Maximum activity was seen on incubation with benzene compared to
      other substrates like TCE, chloroform, toluene, hexane, and petroleum benzene.
      K(m) and V(max) for benzene were 3.8 mM and 340 U/mg/min and those for TCE were
      2.1 mM and 170 U/mg/min. The crude enzyme was partially purified by ammonium
      sulphate precipitation followed by dialysis. Zymogram analysis revealed two
      isoforms in the 70% purified enzyme fraction. The activity stain was more
      prominent when the native gel was incubated in benzene as substrate in comparison
      to TCE. Crude enzyme and purified enzyme fractions were assayed for TCE
      degradation by the Fujiwara test. TCE biotransformation products were analysed by
      FT-IR spectroscopy.

PMID- 24083237
TI  - Prediction of effective drug combinations by chemical interaction, protein
      interaction and target enrichment of KEGG pathways.
AB  - Drug combinatorial therapy could be more effective in treating some complex
      diseases than single agents due to better efficacy and reduced side effects.
      Although some drug combinations are being used, their underlying molecular
      mechanisms are still poorly understood. Therefore, it is of great interest to
      deduce a novel drug combination by their molecular mechanisms in a robust and
      rigorous way. This paper attempts to predict effective drug combinations by a
      combined consideration of: (1) chemical interaction between drugs, (2) protein
      interactions between drugs' targets, and (3) target enrichment of KEGG pathways.
      A benchmark dataset was constructed, consisting of 121 confirmed effective
      combinations and 605 random combinations. Each drug combination was represented
      by 465 features derived from the aforementioned three properties. Some feature
      selection techniques, including Minimum Redundancy Maximum Relevance and
      Incremental Feature Selection, were adopted to extract the key features. Random
      forest model was built with its performance evaluated by 5-fold cross-validation.
      As a result, 55 key features providing the best prediction result were selected.
      These important features may help to gain insights into the mechanisms of drug
      combinations, and the proposed prediction model could become a useful tool for
      screening possible drug combinations. 

PMID- 24083238
TI  - Genome instability at common fragile sites: searching for the cause of their
      instability.
AB  - Common fragile sites (CFS) are heritable nonrandomly distributed loci on human
      chromosomes that exhibit an increased frequency of chromosomal breakage under
      conditions of replication stress. They are considered the preferential targets
      for high genomic instability from the earliest stages of human cancer
      development, and increased chromosome instability at these loci has been observed
      following replication stress in a subset of human genetic diseases. Despite their
      biological and medical relevance, the molecular basis of CFS fragility in vivo
      has not been fully elucidated. At present, different models have been proposed to
      explain how instability at CFS arises and multiple factors seem to contribute to
      their instability. However, all these models involve DNA replication and suggest
      that replication fork stalling along CFS during DNA synthesis is a very frequent
      event. Consistent with this, the maintenance of CFS stability relies on the ATR
      dependent checkpoint, together with a number of proteins promoting the recovery
      of stalled replication forks. In this review, we discuss mainly the possible
      causes that threaten the integrity of CFS in the light of new findings, paying
      particular attention to the role of the S-phase checkpoint. 

PMID- 24083239
TI  - Aptamers: novel molecules as diagnostic markers in bacterial and viral
      infections?
AB  - Worldwide the entire human population is at risk of infectious diseases of which
      a high degree is caused by pathogenic protozoans, worms, bacteria, and virus
      infections. Moreover the current medications against pathogenic agents are losing
      their efficacy due to increasing and even further spreading drug resistance.
      Therefore, there is an urgent need to discover novel diagnostic as well as
      therapeutic tools against infectious agents. In view of that, the Systematic
      Evolution of Ligands by Exponential Enrichment (SELEX) represents a powerful
      technology to target selectively pathogenic factors as well as entire bacteria or
      viruses. SELEX uses a large combinatorial oligonucleic acid library (DNA or RNA)
      which is processed a by high-flux in vitro screen of iterative cycles. The
      selected ligands, termed aptamers, are characterized by high specificity and
      affinity to their target molecule, which are already exploited in diagnostic and
      therapeutic applications. In this minireview we will discuss the current status
      of the SELEX technique applied on bacterial and viral pathogens. 

PMID- 24083240
TI  - Acetylsalicylic Acid reduces the severity of dextran sodium sulfate-induced
      colitis and increases the formation of anti-inflammatory lipid mediators.
AB  - The role of non-steroidal anti-inflammatory drugs in inflammatory bowel disease
      is controversial, as they have been implicated in disease aggravation. Different
      from other cyclooxygenase inhibitors, acetylsalicylic acid (ASA) enhances the
      formation of anti-inflammatory and proresolution lipoxins derived from
      arachidonic acid as well as resolvins from omega-3 polyunsaturated fatty acids
      such as docosahexaenoic acid (DHA). In this study, we examined the effect of ASA
      on murine dextran sodium sulfate colitis. A mouse magnetic resonance imaging
      (MRI) protocol and post mortem assessment were used to assess disease severity,
      and lipid metabolites were measured using liquid chromatography-coupled tandem
      mass spectrometry. Decreased colitis activity was demonstrated by phenotype and
      MRI assessment in mice treated with ASA, and confirmed in postmortem analysis.
      Analysis of lipid mediators showed sustained formation of lipoxin A4 and an
      increase of DHA-derived 17-hydroxydocosahexaenoic acid (17-HDHA) after treatment
      with ASA. Furthermore, in vitro experiments in RAW264.7 murine macrophages
      demonstrated significantly increased phagocytosis activity after incubation with
      17-HDHA, supporting its proresolution effect. These results show a protective
      effect of ASA in a murine colitis model and could give a rationale for a careful
      reassessment of ASA therapy in patients with inflammatory bowel disease and
      particularly ulcerative colitis, possibly combined with DHA supplementation. 

PMID- 24083241
TI  - Promoter hypermethylation of the EMP3 gene in a series of 229 human gliomas.
AB  - The epithelial membrane protein 3 (EMP3) is a candidate tumor suppressor gene in
      the critical region 19q13.3 for several solid tumors, including tumors of the
      nervous systems. The aim of this study was to investigate the EMP3 promoter
      hypermethylation status in a series of 229 astrocytic and oligodendroglial tumors
      and in 16 GBM cell lines. The analysis was performed by methylation-specific PCR
      and capillary electrophoresis. Furthermore, the EMP3 expression at protein level
      was evaluated by immunohistochemistry and Western blotting analysis. Associations
      of EMP3 hypermethylation with total 1p/19q codeletion, MGMT promoter
      hypermethylation, IDH1/IDH2 and TP53 mutations, and EGFR amplification were
      studied, as well as its prognostic significance. The EMP3 promoter
      hypermethylation has been found in 39.5% of gliomas. It prevailed in low-grade
      tumors, especially in gliomas with an oligodendroglial component, and in sGBMs
      upon pGBMs. In oligodendroglial tumors, it was strongly associated with both
      IDH1/IDH2 mutations and total 1p/19q codeletion and inversely with EGFR gene
      amplification. No association was found with MGMT hypermethylation and TP53
      mutations. In the whole series, the EMP3 hypermethylation status correlated with
      19q13.3 loss and lack of EMP3 expression at protein level. A favorable prognostic
      significance on overall survival of the EMP3 promoter hypermethylation was found
      in patients with oligodendroglial tumors. 

PMID- 24083242
TI  - Effects of anesthesia and species on the uptake or binding of radioligands in
      vivo in the Gottingen minipig.
AB  - Progress in neuroscience research often involves animals, as no adequate
      alternatives exist to animal models of living systems. However, both the
      physiological characteristics of the species used and the effects of anesthesia
      raise questions of common concern. Here, we demonstrate the confounding
      influences of these effects on tracer binding in positron emission tomography
      (PET). We determined the effects of two routinely used anesthetics (isoflurane
      and propofol) on the binding of two tracers of monoamine function,
      [(11)C]SCH23390, a tracer of the dopamine D1 and D5 receptors, and the alpha2
      adrenoceptor antagonist, [(11)C]yohimbine, in Gottingen minipigs. The kinetics of
      SCH23390 in the pigs differed from those of our earlier studies in primates. With
      two different graphical analyses of uptake of SCH23390, the initial clearance
      values of this tracer were higher with isoflurane than with propofol anesthesia,
      indicative of differences in blood flow, whereas no significant differences were
      observed for the volumes of distribution of yohimbine. The study underscores the
      importance of differences of anesthesia and species when the properties of
      radioligands are evaluated under different circumstances that may affect blood
      flow and tracer uptake. These differences must be considered in the choice of a
      particular animal species and mode of anesthesia for a particular application. 

PMID- 24083243
TI  - Modeling of the renal kinetics of the AT1 receptor specific PET radioligand
      [11C]KR31173.
AB  - PURPOSE: The radioligand [(11)C]KR31173 has been introduced for PET imaging of
      the angiotensin II subtype 1 receptor (AT1R). The purpose of the present project
      was to employ and validate a compartmental model for quantification of the
      kinetics of this radioligand in a porcine model of renal ischemia followed by
      reperfusion (IR). PROCEDURES: Ten domestic pigs were included in the study: five
      controls and five experimental animals with IR of the left kidney. To achieve IR,
      acute ischemia was created with a balloon inserted into the left renal artery and
      inflated for 60 minutes. Reperfusion was achieved by deflation and removal of the
      balloon. Blood chemistries, urine specific gravity and PH values, and circulating
      hormones of the renin angiotensin system were measured and PET imaging was
      performed one week after IR. Cortical time-activity curves obtained from a 90 min
      [(11)C]KR31173 dynamic PET study were processed with a compartmental model that
      included two tissue compartments connected in parallel. Radioligand binding
      quantified by radioligand retention (80 min value to maximum value ratio) was
      compared to the binding parameters derived from the compartmental model. A
      binding ratio was calculated as DVR = DV(S)/DV(NS), where DV(S) and DV(NS)
      represented the distribution volumes of specific binding and nonspecific binding.
      Receptor binding was also determined by autoradiography in vitro. RESULTS:
      Correlations between rate constants and binding parameters derived by the
      convolution and deconvolution curve fittings were significant (r > 0.9). Also
      significant was the correlation between the retention parameter derived from the
      tissue activity curve (Y(ret)) and the retention parameter derived from the
      impulse response function (f(ret)). Furthermore, significant correlations were
      found between these two retention parameters and DVR. Measurements with PET
      showed no significant changes in the radioligand binding parameters caused by IR,
      and these in vivo findings were confirmed by autoradiography performed in vitro.
      CONCLUSIONS: Correlations between various binding parameters support the concept
      of the parallel connectivity compartmental model. If an arterial input function
      cannot be obtained, simple radioligand retention may be adequate for estimation
      of in vivo radioligand binding.

PMID- 24083244
TI  - Comparative analyses of the beta-tubulin gene and molecular modeling reveal
      molecular insight into the colchicine resistance in kinetoplastids organisms.
AB  - Differential susceptibility to microtubule agents has been demonstrated between
      mammalian cells and kinetoplastid organisms such as Leishmania spp. and
      Trypanosoma spp. The aims of this study were to identify and characterize the
      architecture of the putative colchicine binding site of Leishmania spp. and
      investigate the molecular basis of colchicine resistance. We cloned and sequenced
      the beta-tubulin gene of Leishmania (Viannia) guyanensis and established the
      theoretical 3D model of the protein, using the crystallographic structure of the
      bovine protein as template. We identified mutations on the Leishmania beta
      tubulin gene sequences on regions related to the putative colchicine-binding
      pocket, which generate amino acid substitutions and changes in the topology of
      this region, blocking the access of colchicine. The same mutations were found in
      the beta-tubulin sequence of kinetoplastid organisms such as Trypanosoma cruzi,
      T. brucei, and T. evansi. Using molecular modelling approaches, we demonstrated
      that conformational changes include an elongation and torsion of an alpha-helix
      structure and displacement to the inside of the pocket of one beta-sheet that
      hinders access of colchicine. We propose that kinetoplastid organisms show
      resistance to colchicine due to amino acids substitutions that generate
      structural changes in the putative colchicine-binding domain, which prevent
      colchicine access.

PMID- 24083245
TI  - A novel Fuzzy Expert System for the identification of severity of carpal tunnel
      syndrome.
AB  - The diagnosis of carpal tunnel syndrome, a peripheral nerve disorder, at the
      earliest possible stage is very crucial because if left untreated it may cause
      permanent nerve damage reducing the chances of successful treatment. Here a novel
      Fuzzy Expert System designed using MATLAB is proposed for identification of
      severity of CTS. The data used were the nerve conduction study data obtained from
      Kannur Medical College, India. It consists of thirteen input fields, which
      include the clinical values of the diagnostic test and the clinical symptoms, and
      the output field gives the disease severity. The results obtained match with the
      expert's opinion with 98.4% accuracy and high degrees of sensitivity and
      specificity. Since quantification of the intensity of CTS is a crucial step in
      the electrodiagnostic procedure and is important for defining prognosis and
      therapeutic measures, such an expert system can be of immense use in those
      regions where the service of such specialists may not be readily available. It
      may also prove useful in combination with other systems in providing diagnostic
      and predictive medical opinions and can add value if introduced into the routine
      clinical consultations to arrive at the most accurate medical diagnosis in a
      timely manner. 

PMID- 24083246
TI  - Structural and sequence similarities of hydra xeroderma pigmentosum A protein to
      human homolog suggest early evolution and conservation.
AB  - Xeroderma pigmentosum group A (XPA) is a protein that binds to damaged DNA,
      verifies presence of a lesion, and recruits other proteins of the nucleotide
      excision repair (NER) pathway to the site. Though its homologs from yeast,
      Drosophila, humans, and so forth are well studied, XPA has not so far been
      reported from protozoa and lower animal phyla. Hydra is a fresh-water cnidarian
      with a remarkable capacity for regeneration and apparent lack of organismal
      ageing. Cnidarians are among the first metazoa with a defined body axis, tissue
      grade organisation, and nervous system. We report here for the first time
      presence of XPA gene in hydra. Putative protein sequence of hydra XPA contains
      nuclear localization signal and bears the zinc-finger motif. It contains two
      conserved Pfam domains and various characterized features of XPA proteins like
      regions for binding to excision repair cross-complementing protein-1 (ERCC1) and
      replication protein A 70 kDa subunit (RPA70) proteins. Hydra XPA shows a high
      degree of similarity with vertebrate homologs and clusters with deuterostomes in
      phylogenetic analysis. Homology modelling corroborates the very close similarity
      between hydra and human XPA. The protein thus most likely functions in hydra in
      the same manner as in other animals, indicating that it arose early in evolution
      and has been conserved across animal phyla.

PMID- 24083247
TI  - 3D-culture system for heart regeneration and cardiac medicine.
AB  - 3D cultures have gained attention in the field of regenerative medicine for their
      usefulness as in vitro model of solid tissues. Bottom-up technology to generate
      artificial tissues or organs is prospective and an attractive approach that will
      expand as the field of regenerative medicine becomes more translational. We have
      characterized c-kit positive cardiac stem cells after long-term cultures and
      established a 3D-nanoculture system using collagen scaffolds. By combining
      informatics-based studies, including proteomic analyses and microarrays, we
      sought to generate methods that modeled cardiac regeneration which can ultimately
      be used to build artificial hearts. Here, we describe the use of biodegradable
      beads or 3D cultures to study cardiac regeneration. We summarize recent work that
      demonstrates that, by using a combination of molecular analyses with 3D cultures,
      it is possible to evaluate concise mechanisms of solid tissue stem cell biology. 

PMID- 24083249
TI  - Human body fluid.

PMID- 24083248
TI  - Metabolism, physiological role, and clinical implications of sphingolipids in
      gastrointestinal tract.
AB  - Sphingolipids in digestive system are responsible for numerous important
      physiological and pathological processes. In the membrane of gut epithelial
      cells, sphingolipids provide structural integrity, regulate absorption of some
      nutrients, and act as receptors for many microbial antigens and their toxins.
      Moreover, bioactive sphingolipids such as ceramide or sphingosine-1-phosphate
      regulate cellular growth, differentiation, and programmed cell death-apoptosis.
      Although it is well established that sphingolipids have clinical implications in
      gastrointestinal tumorigenesis or inflammation, further studies are needed to
      fully explore the role of sphingolipids in neoplastic and inflammatory diseases
      in gastrointestinal tract. Pharmacological agents which regulate metabolism of
      sphingolipids can be potentially used in the management of colorectal cancer or
      inflammatory bowel diseases. The aim of this work is to critically the review
      physiological and pathological roles of sphingolipids in the gastrointestinal
      tract. 

PMID- 24083251
TI  - Assessing the micronutrient and macronutrient intakes in female students and
      comparing them with the set standard values.
AB  - BACKGROUND: Healthy nutrition particularly the energy intake and the essential
      nutrients in female students is very important. This study aims to assess micro-
      and macronutrient intakes in female students of Isfahan University of Medical
      Sciences, Iran. MATERIALS AND METHODS: This cross-sectional study involved 100
      female students aged between 18 and 25 years in 2008-2009. Anthropometrics
      measures were performed and two 24-hours food recalls were used to collect the
      dietary information and were analyzed using food processor 2 and compared with
      the dietary reference intakes (DRIs) 2008. FINDINGS: As many as 61.1% of subjects
      resided in dormitories; 12.7% were married. Prevalence of overweight or obesity
      and abdominal obesity in the subjects studied were 6.9% and 46.1%, respectively.
      The mean (+/-SD) systolic blood pressure was 105.2 +/- 15.6 mmHg and the
      diastolic was 62.2 +/- 10.4 mmHg. Totally, 3.9% of the subjects had hypertension.
      Food intake analysis indicated that B12, folate, magnesium, potassium, and
      calcium were below the recommended level, and vitamin C, E, pantothenic acid, B1,
      B3, phosphate, and zinc were above, and energy intake, macronutrient, vitamin A,
      pyridoxine, iron, and selenium were, in general, adequate. CONCLUSION: The
      findings of the study indicated that macronutrients intake was appropriate, but
      the problem mainly existed in the consumption of micronutrients. It is
      recommended to increase the intakes of important food groups such as dairy,
      vegetable, and fruit that are proper sources of micronutrients, and it is also
      suggested to improve strategies and the competence in this area of nutrition.

PMID- 24083252
TI  - Relationship between junk foods intake and weight in 6-7 years old children,
      Shahin Shahr and Meymeh, Iran.
AB  - BACKGROUND: Healthy nutrition is very important considering the weight status
      especially in children. The aim of this study was to assess the relationship
      between junk foods intake and weight in 6-7-years old children. MATERIALS AND
      METHODS: This cross-sectional study was carried out in Shahin Shahr and Meymeh,
      Iran, in 2009. Anthropometrics measures were done and 24-hour food recall used
      for dietary information and analyzed with food processor 2 and then compared with
      dietary reference intakes 2008 (DRI). FINDINGS: 61.1 percent of the subjects were
      residing in dormitories and 12.7 percent were marred. Prevalence of overweight or
      obesity and abdominal obesity was 6.9 percent and 46.1 percent respectively. Mean
      (+/-SD) systolic blood pressure was 105.2 +/- 15.6 mm/Hg and diastolic was 62.2
      +/- 10.4 mm/Hg. Totally, 3.9 percent of the subjects had hypertension. The
      analysis of food intake indicate that (B12, folate, magnesium, potassium,
      calcium) with level below the recommended ones, and (vitamin C, E, pantothenic
      acid, B1, B3, phosphate, zinc) with up levels the recommended ones, and energy
      intake, macronutrient, vitamin A, pyridoxine, iron, selenium were in general
      appropriate. CONCLUSION: These results indicated appropriate level of
      macronutrients intake and unbalance mainly existed in micronutrients. It is
      recommended to increase intake important food groups such as dairy, vegetable,
      fruit that include good source of micronutrients, and also it is suggested that
      need for strategies can improve competence in the area of nutrition.

PMID- 24083253
TI  - The effectiveness of educational intervention based on PRECEDE model on the level
      of stress among the elderly at elderly clubs.
AB  - INTRODUCTION: The elderly are vulnerable to negative effects of stress factors;
      so, the present study was conducted to determine the effect of educational
      intervention based on the PRECEDE model on stress level of the elderly and to
      control stress factors. MATERIALS AND METHODS: In this quasi-experimental study,
      94 elderly people from the clubs for the elderly in Tehran were randomly divided
      into case and control groups in 2008-2009. Planning for the educational program
      was done according to the PRECEDE model. Before implementing the program, valid
      and reliable depression, anxiety, and stress questionnaires (DASS 21) were
      completed for both groups. The experimental group received the educational
      intervention based on the PRECEDE model (eight sessions, one session per week),
      and both groups were followed up two months after the intervention (the previous
      questionnaires were filled again). DASS 21 Scoring and Interpretation Generator
      was used for calculating scores of the questionnaires. Finally, the data obtained
      were analyzed by the SPSS 15 software using t-test, paired t-test, and Mann
      Whitney test at a significant level of P<=0.05. RESULTS: The findings showed
      significant differences between the experimental group and control group in terms
      of predisposing factors of knowledge (P<=0.001) and attitude (P<=0.001), enabling
      factors (P<=0.001), reinforcing factors (P<=0.001), and functioning especially in
      deep breathing and relaxation techniques (P<=0.001). Mean scores and severity of
      stress were significant after the intervention (P<=0.001). CONCLUSION: The
      findings of the present study confirmed the effectiveness of the PRECEDE model
      based educational program on preventing or reducing stress level in the elderly.

PMID- 24083254
TI  - Effect of educational intervention on physical activity-related knowledge,
      attitude and behavior of among first-grade students of male high schools.
AB  - INTRODUCTION: Regular physical activity has positive effects on physical, mental
      and social aspects of individual and community health. Considering the prevalence
      of noncommunicable diseases such as primary hypertension, osteoporosis and
      cardiovascular diseases for which sedentary lifestyle is a responsible factor,
      health policy makers have planned to encourage people to do more physical
      activities. Development of beneficial health habits during childhood and early
      adolescence are very important because the behaviors, which start at adolescence
      tend to continue into adulthood, too. This study aimed to determine the effect of
      educational intervention on physical activity-related knowledge, attitude and
      behavior of the first grade students in male high schools of Bavanat in 2010.
      MATERIALS AND METHODS: In this prospective experimental study, after selecting
      two qualified schools from five high schools, all students of one school (two
      classes including 42 individuals) were randomly assigned to the experimental
      group and all the students of another high school (two classes including 43
      individuals) were randomly assigned to the control group. The data gathering tool
      was a 4-section questionnaire which included demographic questions, knowledge-
      and attitude-related questions and the questionnaire of physical activity
      performance. The first three sections of the questionnaire were the researcher
      designed and validated by face and content validity. Test-retest and internal
      consistency (Cronbach's Alpha) methods were used to determine the reliability of
      knowledge questionnaire and attitude questionnaire, respectively. For the
      measurement of physical activity behavior, a self-reporting questionnaire (valid
      and reliable Garcia scale) was used in this study. After conducting the pretest,
      the educational intervention was done for the experimental group. Post-tests were
      conducted immediately and 1 month after intervention. The collected data were
      analyzed using SPSS18 statistical software (independent t-test, paired t-test,
      chi-square, Mann-Whitney test and repeated measures ANOVA). The participants
      voluntarily and consciously participated in this study. RESULTS: The findings
      indicated no significant differences between the groups in terms of mean scores
      of knowledge (P = 0.934), attitude (P = 0.155) and behavior (P = 0.387) before
      the intervention. There was a significant difference between mean scores of
      knowledge in the immediate follow-up (P< 0.001) and 1 month after intervention
      follow-up (P < 0.001), and also between mean scores of attitude immediately (P <
      0.001) and 1 month after intervention (P = 0.01) follow-ups in the experimental
      group compared with the control one. Mean scores of physical activity 1 month
      after the intervention in both experimental and control groups significantly
      increased (P < 0.001, P = 0.01, respectively), but the mean scores of physical
      activity between two groups were not significantly different (P = 0.390).
      DISCUSSION AND CONCLUSION: The results indicated the effectiveness of educational
      intervention, consequently increased knowledge and improved attitude of students,
      in the experimental group compared with the control one in terms of physical
      activities; thus, physical activity behavior of intervention group increased.
      Although the mean scores of physical activity in the control group significantly
      increased, other studies should be done which can control and consider
      confounding variables.

PMID- 24083250
TI  - The roles of hyaluronan/RHAMM/CD44 and their respective interactions along the
      insidious pathways of fibrosarcoma progression.
AB  - Fibrosarcomas are rare malignant mesenchymal tumors originating from fibroblasts.
      Importantly, fibrosarcoma cells were shown to have a high content and turnover of
      extracellular matrix (ECM) components including hyaluronan (HA), proteoglycans,
      collagens, fibronectin, and laminin. ECMs are complicated structures that
      surround and support cells within tissues. During cancer progression, significant
      changes can be observed in the structural and mechanical properties of the ECM
      components. Importantly, hyaluronan deposition is usually higher in malignant
      tumors as compared to benign tissues, predicting tumor progression in some tumor
      types. Furthermore, activated stromal cells are able to produce tissue structure
      rich in hyaluronan in order to promote tumor growth. Key biological roles of HA
      result from its interactions with its specific CD44 and RHAMM (receptor for HA
      mediated motility) cell-surface receptors. HA-receptor downstream signaling
      pathways regulate in turn cellular processes implicated in tumorigenesis. Growth
      factors, including PDGF-BB, TGFbeta2, and FGF-2, enhanced hyaluronan deposition
      to ECM and modulated HA-receptor expression in fibrosarcoma cells. Indeed, FGF-2
      through upregulation of specific HAS isoforms and hyaluronan synthesis regulated
      secretion and net hyaluronan deposition to the fibrosarcoma pericellular matrix
      modulating these cells' migration capability. In this paper we discuss the
      involvement of hyaluronan/RHAMM/CD44 mediated signaling in the insidious pathways
      of fibrosarcoma progression.

PMID- 24083255
TI  - Assessing critical thinking in medical sciences students in two sequential
      semesters: Does it improve?
AB  - OBJECTIVES: Critical thinking is an important outcome criterion of higher
      education in any discipline. Medical and paramedical students always encounter
      with many new problems in clinical settings and medicinal laboratory, and
      critical thinking is an essential skill in obtaining a better approach for
      problem solving. We performed a pre-and post-test to evaluate the change of
      critical thinking skills in medical sciences students who enrolled in Isfahan
      University of Medical Sciences in Iran during the academic years 2008-2010.
      METHODS: In a longitudinal design study, the critical thinking skills were
      compared in medical sciences students in two sequential semesters using the
      California Critical Thinking Skills Test. The test is divided into two parts
      (parts 1 and 2), including 17 items in each part. Based on proportional
      stratified sampling, a groups of students (group 1, n=159) were selected from the
      university population, who enrolled in medicine, pharmacy, nursing, and
      rehabilitation colleges. The students in group 1 were asked to complete the part
      1 of the test (phase I). After one semester, another group (group 2, n=138) from
      the same population was randomly selected, and they were asked to complete the
      part two (phase II). The students' demographic data also were recorded. The
      California critical thinking skills test was translated and it validity and
      reliability were approved before. RESULTS: No significant difference was observed
      between the two groups in the demographic data. The students critical thinking
      scores in phase II significantly reduced in comparison with phase 1 (p<0.05). The
      phase II scores in subdivisions of analysis, inference, inductive reasoning, and
      deductive reasoning also failed to demonstrate improvement. CONCLUSION: It seems
      curriculum reform is necessary to improve the students' critical thinking.

PMID- 24083256
TI  - The relationship between depression and quality of life among hemodialysis
      patients in Chaharmahal and Bakhtiari province in the year 2011.
AB  - INTRODUCTION: Although hemodialysis is therapeutic, it causes numerous physical
      and psychological tensions, which affect the quality of life of patients.
      Assessing the quality of life helps to consider clients' problems; basically, the
      relationship between depression and quality of life of patients has been observed
      in this study. MATERIALS AND METHODS: This was an analytic-descriptive study in
      which the patients received hemodialysis in Chaharmahal and Bakhtiari province.
      They were monitored through census method. The data collection instrument was
      questionnaires consisting of demography, Beck Depression Inventory, and WHO
      Quality-of-Life Questionnaire. The obtained data was analyzed by SPSS (Version
      15) and Mann-Whitney test, Chi-square test, and t-independent test. RESULTS:
      Ninety-five men and 76 women (171 totally) receiving hemodialysis treatment
      participated in the study. Chi-square test showed a significant relationship
      between depression and quality of life of these patients (P < 0.05). DISCUSSION:
      Considering the present study results, it is essential to take into account
      depression level and quality of life in planning their care programs.

PMID- 24083257
TI  - Medical records department and balanced scorecard approach.
AB  - CONTEXT: The Medical Records Department (MRD) is an important source for
      evaluating and planning of healthcare services; therefore, hospital managers
      should improve their performance not only in the short-term but also in the long
      term plans. The Balanced Scorecard (BSC) is a tool in the management system that
      enables organizations to correct operational functions and provides feedback
      around both the internal processes and the external outcomes, in order to improve
      strategic performance and outcomes continuously. AIMS: The main goal of this
      study was to assess the MRD performance with BSC approach in a hospital.
      MATERIALS AND METHODS: This research was an analytical cross-sectional study in
      which data was collected by questionnaires, forms and observation. The population
      was the staff of the MRD in a hospital in Najafabad, Isfahan, Iran. STATISTICAL
      ANALYSIS USED: To analyze data, first, objectives of the MRD, according to the
      mission and perspectives of the hospital, were redefined and, second, indicators
      were measured. Subsequently, findings from the performance were compared with the
      expected score. In order to achieve the final target, the programs, activities,
      and plans were reformed. RESULTS: The MRD was successful in absorbing customer
      satisfaction. From a customer perspective, score in customer satisfaction of
      admission and statistics sections were 82% and 83%, respectively. CONCLUSIONS:
      The comprehensive nature of the strategy map makes the MRD especially useful as a
      consensus building and communication tool in the hospital.

PMID- 24083258
TI  - How to teach medical students to critically appraise a published article in the
      public health domain.
AB  - The core part of evidence-based medicine (EBM) is the ability to critically
      appraise published articles on a given subject. Medical students, especially
      within the developing world, usually do not learn how to critically appraise a
      published article since this is not part of their designed curriculum. This paper
      is reporting an innovative approach on how to teach critical appraisal skills to
      medical students, from an Iranian Medical School. 

PMID- 24083259
TI  - Breastfeeding status during the first two years of infants' life and its risk
      factors based on BASNEF model structures in Isfahan.
AB  - BACKGROUND: Breastfeeding depends on social and cultural conditions of societies.
      Behavior,Attitude, Subjective Norms, Enabling Factors (BASNEF) model is one of
      the comprehensive models of behavior study, especially in developing countries.
      This study was performed to investigate the status of breastfeeding during the
      first two years of infants' life and its risk factors through BASNEF model
      structures. MATERIALS AND METHODS: In this cross-sectional descriptive-analytical
      study, 406 mothers with 6-24-month-old babies were selected by multistage cluster
      sampling method. The data were collected using a questionnaire with five sections
      based on the BASNEF model structures. Demographic characteristics of the studied
      population were also recorded and analyzed using Chi-square tests and analysis of
      variance in SPSS18 statistical software. RESULTS: The prevalence of breastfeeding
      was 86.4% (351 mothers). Three hundred and thirty three mothers (82%) had good
      knowledge and there was a significant relationship between knowledge and
      breastfeeding behavior of mothers (P < 0.05). Two hundred and eighty five mothers
      (70.2%) had good and very good attitude in this regard. There was no significant
      relationship between attitude and breastfeeding behavior of mothers (P > 0.05).
      There was a significant relationship between breastfeeding behavior of mothers
      and subjective norms of husbands, mother and mother-in-law (P < 0.05); however,
      no significant relationship was found with regard to enabling factors (P > 0.05).
      Moreover, no significant relationship was observed between type of children
      nutrition and variables of delivery mode, maternal age and number of children (P
      > 0.05). CONCLUSION: In addition to knowledge of nursing mothers, supports and
      encouragement of husbands, mothers and mother-in-laws, as subjective norms of
      behavior, have a positive impact on the breastfeeding behavior of mothers. Thus,
      breastfeeding programs should pay more attention to the role of these mentioned
      factors.

PMID- 24083260
TI  - The effect of nutrition and food hygieneeducation on the knowledge of female
      elementary school teachers in city of ferdows.
AB  - INTRODUCTION: Teachers are one of the most influential groups in elevating social
      health, and their teaching nutritional points to the students can both affect
      students' awareness and the transferring of such nutritional education to the
      families. This study was undertaken tosurvey the influence of nutrition and
      nutritional health education on the awareness of female elementary school
      teachers. MATERIALS AND METHODS: Fifty-seven female elementary school teachers
      were chosen from the Ferdows City for this quasi-experimental study. Prior to the
      outset of the educational workshop, they were asked to fill out a questionnaire
      about nutrition and nutritional health, which was followed by the two-day
      workshop. After two months, they were given a second questionnaire. The results
      were analyzed by paired t-test, ANOVA, and McNemar. In all the tests, a
      significance level alpha = 0.05 was considered. RESULTS: Findings of the study
      showed that the mean score of awareness before interference was 10.98%, which
      reached up to 18.2% after the interference (P < 0.001). With regard to
      theimportance of breakfast intake, the teachers' awareness increased from 57.9 to
      98.2% from before to after intervention, respectively. CONCLUSION: Applying
      interventional methods of education in teacher training centers in conjunction
      with medical and educational centers, with regard to nutrition and nutritional
      health, can elevate the health of students.

PMID- 24083261
TI  - Health-promoting lifestyle and quality of life among undergraduate students at
      school of health, Isfahan university of medical sciences.
AB  - BACKGROUND: Health promoting lifestyle (HPL) focuses on life promotion through
      lifestyle which consists of six aspects of "physical activity", "nutrition",
      "health responsibility", "spiritual growth", "interpersonal relations" and
      "stress management". This lifestyle promotes health and welfare and induces
      satisfaction, self-persuasion and self-improvement. Considering the importance of
      the way a new behavior affects "life quality" as a motivational factor for
      starting and continuing that behavior, this study aimed to determine the
      relationship between health-promoting lifestyle and its aspects. MATERIALS AND
      METHODS: This cross-sectional study was performed on undergraduate students at
      School of Health, Isfahan University of Medical Sciences, using a census method.
      Health promoting lifestyle was measured by Health Promotion Lifestyle Profile two
      and life quality was assessed by the Persian version of QLQ-C30 questionnaire.
      Data analysis was conducted using descriptive and inferential statistical tests
      in SPSS. RESULTS: Mean age of the participants was 21.12 years old. From among
      six aspects of health promoting behaviors, spiritual growth and responsibility
      with the means of 22.01 +/- 2.224 and 20 +/- 2.31 had the highest and physical
      activity with the mean of 17.58 +/- 2.9 had the lowest scores, respectively.
      General life quality of 40.7% students was good and only 19.8% of them had an
      average global life quality. The highest and lowest frequencies of health-related
      life quality belonged to very good (58.6%) and excellent (9%) health,
      respectively. Except for stress management (P = 0.05) and gender of the students,
      there were no significant relationships between other HPL aspects and gender.
      There was no statistically significant relationship between global life quality
      of students and nutrition, physical activity, self-health responsibility and
      stress management while there was a significant relationship between global life
      quality and spiritual growth of the students. Health-related life quality and
      stress management were significantly related to each other; however, no
      statistically significant relationship was observed between health-related life
      quality and nutrition, physical activity, interpersonal relations and spiritual
      growth. CONCLUSION: There is a significant relationship between adopting health
      promoting lifestyle and aspects of spiritual growth and stress management on the
      one hand and general quality of life on the other, at least among students.

PMID- 24083262
TI  - Socio-economic factors and diabetes consequences among patients with type 2
      diabetes.
AB  - BACKGROUND: Considering the effect of socio-economic factors on the emergence of
      chronic diseases and the importance of this aspect of diseases for policy makers
      and authorities of health care organizations, this study tried to investigate the
      role of these factors in type 2 diabetes and its consequences, which can be used
      in health policy making for preventing from this disease. MATERIALS AND METHODS:
      This descriptive-analytical study was conducted on 384 diabetic patients who were
      admitted to a diabetes center in the city of Isfahan. The participants were
      selected using simple random sampling. A questionnaire with 42 questions was used
      for gathering the data which were analyzed using chi-square and Fisher's
      statistical tests. RESULTS: The studied population consisted of 52.1% male and
      47.9% female participants. There was a statistically significant relationship
      between diabetes complications, age group, educational level, job status,
      relationship with family members, number of family visits and the reassurance
      provided by the family, type of leisure time activities, health status, years
      with diabetes, smoking, type of treatment, fried food consumption and income (P <
      0.001), sense of security and communication in living environment (P < 0.002) and
      daily intake of vegetables (P < 0.02). CONCLUSION: It seems that the application
      of supportive resources and secondary strategies is an essential issue in the
      patients with chronic diseases, particularly diabetes. Empowering strategies can
      induce basic changes in order to increase positive expectations, hope, self
      esteem and self- confidence in patients; this is the exact strategy which must be
      used to efficiently control diabetes and its different types of complications
      among patients.

PMID- 24083263
TI  - Epidemiology of animal bite in Aq Qala city, northen of Iran.
AB  - BACKGROUND: Animal bite is one of the problems of public health which has the
      potential risk of rabies disease. This study was conducted to determine the
      epidemiology of animal bite in Aq Qala city from 2000 to 2009. MATERIALS AND
      METHODS: In this descriptive cross-sectional study, 13142 cases of animal bites
      which were recorded in Rabies Treatment Center of Aq Qala City were entered into
      the study by census method. The data were collected from the registered office
      profile of people who had referred to this center. The obtained data were
      analyzed using descriptive statistics (frequency distribution, percentage, mean,
      and standard deviation) and Chi-square test. FINDINGS: Of 13142 registered cases,
      72.1% were men and 27.9% were women. The mean age of the victims was 25.0 +/-
      17.8 years, most of whom (84%) lived in villages. Also, most cases of animal bite
      were done by dogs, (97.8%) occurred in legs (69.6%). Most of the victims were
      students (28.9%). The highest frequency of bites happened in spring (28.8%). The
      incidence rate of animal bite was 1222/100,000 people. The highest and lowest
      incidence rates were 1608/100 000 in 2004 and 1117/100,000 in 2009, respectively.
      There was a significant relationship between season and the number of bites (P <
      0.05). CONCLUSION: The incidence of animal bite in Aq Qala city was higher than
      that in other studies in different parts of the country. Considering the high
      cost of antirabies serum and vaccination, it is essential to take necessary
      measures reduce the incidence of this problem.

PMID- 24083264
TI  - Noise exposure as a risk factor of cardiovascular diseases in workers.
AB  - INTRODUCTION: Workers in different jobs are exposed to noise, which can affect
      hearing loss and sleep disturbance in the long term. Excessive noise exposure may
      lead to increased blood pressure, reduced efficiency, and increased absenteeism.
      MATERIALS AND METHODS: In this case-control study, 80 workers were studied in
      terms of noise exposure and blood pressure. Noise exposure was measured by SEL
      440 sound level meters according to ISO 1996 standard. Blood pressure of the case
      and control groups was measured in workplace, under standard circumstances, using
      ALPK2 mercury sphygmomanometer during physical examination. Data were analyzed by
      t-test and Pearson's correlation coefficient. RESULTS: Mean level of noise was
      95.21 +/- 2.56 db, which was significantly higher than permitted limit of 85 db
      (ACGIH 2009) (P < 0.01). Diastolic blood pressure was normal in 28.8% and high in
      50.1%, and between these in 21.1% of workers. Mean difference of systolic blood
      pressure in two studied groups (P < 0.01) was meaningful. However, mean
      difference of diastolic blood pressure was not significant in two studied groups
      (P > 0.05). There was a positive and weak relationship between noise and systolic
      blood pressure (r = 0.28, P < 0.006). CONCLUSION: Prolonged exposure to
      industrial noise is related with high blood pressure as a risk factor of
      cardiovascular diseases. Therefore, it is recommended that training programs be
      held for workers, preventive measures for noise exposure at workplace be taken,
      blood pressure of workers be attended to and special care be given to workers
      with a history of hypertension.

PMID- 24083265
TI  - The effectiveness of nutrition education program based on health belief model
      compared with traditional training.
AB  - INTRODUCTION: This study was aimed to compare the effect of nutrition educational
      program based on HBM with traditional education recommended weight gain among
      pregnant women in Gonabad. Target population was pregnant women who were resided
      in Gonabad and went to urban health care centers for prenatal cares. MATERIALS
      AND METHODS: 110 pregnant women (case group: 54, control group: 56) were selected
      who had come to this centers in the first stage of prenatal care (6th -10th week
      of pregnancy) in 1388 and were consequently classified in case and control group.
      There is no significant difference for age, education, number of parity, history
      of abortion and job between case and control groups. RESULTS: There was no
      significant differences in nutritional behavior mean score before intervention in
      case (74.42 +/- 12.78) and control (77.14 +/- 15.35) groups (P value = 0.82,
      independent t- test); but after education, intervention was significant in
      nutritional behavior between two groups (P value = 0.01, independent t-test);
      DISCUSSION: after intervention, there also was significant difference in HBM
      structures mean score in case group compare with control group and the highest
      rise in score was related to perceived benefits (15.13 increment).

PMID- 24083266
TI  - Association between dairy and calcium intake and general and central obesity
      among female students.
AB  - BACKGROUND: Nowadays, obesity is considered a worldwide problem. Although
      genetics is one of the factors associated with obesity, its predisposing factors
      include nutritional and environmental factors. Several studies have addressed the
      relationship between nutritional factors and general and central adiposity.
      Therefore, the purpose of this study was to determine the relationship between
      the consumption of dairy products and prevalence of obesity and central obesity
      in young female university students at the Isfahan University of Medical
      Sciences. MATERIALS AND METHODS: This cross-sectional study was conducted on 236
      healthy female university students in the age range of 18 and 30 years who were
      selected randomly from among the students at the Isfahan University of Medical
      Sciences, Iran. A previously validated semiquantitative food questionnaire was
      used to assess their entire dietary component intake. Physical activity was
      evaluated by recording daily physical activities. FINDINGS: The prevalence of
      obesity, central adiposity, and excess weight was 1.7, 0.9, and 8.1%,
      respectively. The mean values of body mass index (BMI) and waist circumference
      were 21.54 kg/m(2) and 70.37 cm, respectively. Moreover, the mean value of dairy
      product consumption was 444.24 g/day. The results showed no significant
      relationship between dairy or calcium intake and weight and waist circumference
      as well as prevalence of obesity, central adiposity, and excess weight (P>0.05).
      CONCLUSION: There was no significant relationship between the consumption of
      dairy products and calcium intake and excess weight, obesity, and central
      adiposity among female university students. However, this study is important in
      that the prevalence of obesity, central adiposity, and excess weight along with
      the mean values of BMI and waist circumference are reported.

PMID- 24083267
TI  - Investigation of retention and destruction process of medical records in the
      hospitals and codifying appropriate guidelines.
AB  - INTRODUCTION: One of the major issues in hospitals is the period for which the
      medical records are retained. Health information management professionals
      traditionally have performed retention and destruction functions using all media,
      including paper, images, optical disk, microfilm, DVD, and CD-ROM. Health
      information management departments must maintain a specific program to retain and
      destruct the records. The purpose of this paper is to investigate the retention
      and destruction process of medical records in the hospitals in Isfahan and
      codifying the appropriate guidelines. MATERIALS AND METHODS: The research was
      conducted as a cross-sectional descriptive study in 30 hospitals in Isfahan. The
      data was collected using a Check List. Also 30 medical records experts'
      viewpoints were obtained using the Delphi technique. Data entry and statistical
      analysis was performed using SPSS. RESULTS: The findings indicated that 53.8% of
      the study population maintained a written policy. A 34.6% maintained a written
      policy to destruct medical records. And 50% announced that no instructions had
      been given to the hospitals by qualified authorities to destruct the medical
      records. DISCUSSION: The majority of the hospitals are still unclear about the
      retention period of medical records, which could be due to not to mention the
      retention period for most medical records by the country's National Literature
      and lack of policy and procedure in hospitals. CONCLUSIONS: According to the
      legislations, hospitals are bound to retain the inpatients' records for full 15
      years but based on the findings of this research, less than half of the study
      population retained the inpatients' records for the period mentioned.

PMID- 24083268
TI  - Physical activity stage-matched intervention: Promoting metabolic control in type
      2 diabetes.
AB  - BACKGROUND: Regular physical activity has an important role in reducing
      cardiovascular risk factors and improving metabolic control in patients with type
      2 diabetes. This study aims to investigate the effect of physical activity stage
      matched intervention on metabolic control in type 2 diabetes patients. MATERIALS
      AND METHODS: An 8-week physical activity program conducted with 50 type 2
      diabetes females who were physically inactive and in precontemplation,
      contemplation, and preparation stages of change. Participants were divided into
      intervention and control groups (each group, n = 25). Data were collected by
      physical activity stage of change questionnaire and metabolic factors were
      measured by laboratory tests before initiation program. Subsequently, stage
      matched physical activity program was conducted for the interventional group.
      Control group received routine education from the diabetes center. After 8 weeks,
      physical activity questionnaire filled out by participants and metabolic factors
      were evaluated by a laboratory test. RESULTS: Findings showed patients in the
      intervention group and compared with control group significantly moved through
      stages of change after physical activity program (P-value < 0.05). Evaluation of
      physical activity after educational program demonstrated that the intervention
      group adopted regular physical activity more than the control group and also the
      difference between groups was significant (P-value < 0.05). Our findings indicate
      a significant relationship between physical activity level and moving in stages
      of change in the intervention group (P-value < 0.05). Comparison of metabolism
      factors after physical activity program showed significant decrease in
      glycosilated hemoglobin in the intervention group than the control group (P-value
      < 0.05). However, significant differences between groups were not observed in
      other metabolism factors. CONCLUSION: Designing and implementing physical
      activity stage-matched intervention can improve metabolic control and management
      of type 2 diabetes.

PMID- 24083269
TI  - Assessment of physical activity in medical and public health students.
AB  - BACKGROUND: Reduced level of physical activity, as an important problem of
      urbanization and industrial development, has a considerable impact on the
      population morbidity and mortality. The rate of inactivity has been reported to
      be 60-85% in adults worldwide. Considering the importance of physical activity
      among youth, the aim of this study was to evaluate the physical activity among
      university students. MATERIALS AND METHODS: In this cross-sectional study
      physical activity was assessed in 399 medical and public health students of
      Isfahan University of Medical Sciences, Iran. Physical activity was evaluated by
      standard questionnaire in four fields containing job, transport, work, and
      leisure time at home. FINDINGS: Regarding moderate physical activity, 48.6% of
      students were active and the rest were inactive. Regarding severe physical
      activity, 32.6% were active and the rest were inactive. Mean number of hours for
      moderate activity per day was 1.96 +/- 0.19 h/day in the last 7 days. There was a
      significant relationship between physical activity and sex and students' course
      of study. CONCLUSION: The results indicated that the level of physical activity
      was not sufficient among students; therefore, considering its importance among
      students, it is necessary to educate them regarding lifestyle modification
      specially to increase the level of physical activity during their leisure time.

PMID- 24083270
TI  - The relationship between computer games and quality of life in adolescents.
AB  - BACKGROUND: Term of doing computer games among teenagers is growing rapidly. This
      popular phenomenon can cause physical and psychosocial issues in them. Therefore,
      this study examined the relationship between computer games and quality of life
      domains in adolescents aging 12-15 years. MATERIALS AND METHODS: In a cross
      sectional study using the 2-stage stratified cluster sampling method, 444 male
      and female students in Borkhar were selected. The data collection tool consisted
      of 1) World Health Organization Quality Of Life - BREF questionnaire and 2)
      personal information questionnaire. The data were analyzed by Pearson
      correlation, Spearman correlation, chi-square, independent t-tests and analysis
      of covariance. FINDINGS: The total mean score of quality of life in students was
      67.11+/-13.34. The results showed a significant relationship between the age of
      starting to play games and the overall quality of life score and its fourdomains
      (range r=-0.13 to -0.18). The mean of overall quality of life score in computer
      game users was 68.27+/-13.03 while it was 64.81+/-13.69 among those who did not
      play computer games and the difference was significant (P=0.01). There were
      significant differences in environmental and mental health domains between the
      two groups (P<0.05). However, there was no significant relationship between BMI
      with the time spent and the type of computer games. CONCLUSION: Playing computer
      games for a short time under parental supervision can have positive effects on
      quality of life in adolescents. However, spending long hours for playing computer
      games may have negative long-term effects.

PMID- 24083271
TI  - The evaluation of Mothers' participation project in children's growth and
      development process: Using the CIPP evaluation model.
AB  - BACKGROUND: Assessment of national children's growth indicated a high prevalence
      of growth failure among them. Many previous projects have studied the children's
      growth and nutrition status; but most of them leave it without evaluation. The
      aim of this study was to evaluate Mothers' Participation Project that carried out
      in Isfahan after passing two years. MATERIALS AND METHODS: In this descriptive
      and summative evaluation study, 90 mother and child pairs were enrolled. They
      were studied in two case and control groups. We used CIPP Evaluation Model
      (Context, Input, Process, Product). Data collected using children growth chart
      and questionnaire was used in the project. Obtained data were analyzed by
      nonparametric statistical tests. RESULTS: The results showed significant
      differences between the two groups in following items; mean of maternal self
      esteem (P < 0.001), maternal performance in training others (P = 0.006), weekly
      study time (P = 0.004), frequency of mothers participation in education programs
      (P = 0.002), their knowledge about the growth monitoring card (P = 0.03), their
      ability in drawing growth curves (P < 0.001), mothers knowledge about types of
      growth curves (P = 0.001) and the objectives of growth monitoring (P < 0.001).
      CONCLUSION: Considering the sustained improvement of maternal knowledge and
      function regarding children's growth and development after two years of
      participation in the project, the performance of CIPP model was confirmed in this
      field.

PMID- 24083272
TI  - Academic failure and students' viewpoint: The influence of individual, internal
      and external organizational factors.
AB  - BACKGROUND: Educational failure is one of the most important problems in higher
      education institutes in Iran. This study was performed to investigate the factors
      affecting students' academic failure in Isfahan University of Medical Sciences.
      MATERIALS AND METHODS: In this cross-sectional descriptive study, 280 students of
      Isfahan University of Medical Sciences were studied in 2009. They were chosen
      using multiple cluster sampling. The students' demographic characteristics and
      study information were collected by a valid and reliable questionnaire. Data were
      analyzed with SPSS (15) software. RESULTS: The most important factors affecting
      educational failure from students' point of view were: curriculum (4.23 +/-
      0.63), factors related to educator (3.88 +/- 0.55), learning environment (3.63 +/
      0.62), family factors (3.53 +/- 0.6), socioeconomic factors (3.45 +/- 0.69).
      There is a significant relationship between attitudes of students in two sexes
      and educator (P = 0.03) and socioeconomic environment (P = 0.003). In addition,
      the results did not show a significant difference between attitudes of students
      with age, marital status and employment status (P > 0.05). CONCLUSION: More
      attention to curriculum, factors related to educator and learning environment can
      prevent students' educational failure, in addition to preventing loss of
      resources and contribute to develop a more effective educational system.

PMID- 24083273
TI  - Knowledge, beliefs and preventive behaviors regarding Influenza A in students: a
      test of the health belief model.
AB  - BACKGROUND: The higher prevalence rate of influenza A among adolescence
      emphasizes the importance of preventative strategies among this age group of
      population. The aim of this study was to evaluate the preventive behaviors of
      high school students regarding type A influenza, in Shahrekord, Iran. MATERIALS
      AND METHODS: In this cross-sectional study, 313 high school students were
      enrolled. Preventive behaviors of influenza A was evaluated by components of the
      Health Belief Model (HBM), using a questionnaire which its reliability was
      verified through a pilot study (alpha score 0.8). Data analysis was done by
      descriptive statistics, independent t-test and Pearson correlation coefficient.
      FINDINGS: Mean age of the students was 16.31 years. Knowledge, perceived severity
      and perceived barriers were in the modest level among the students. The highest
      scores were related to perceived susceptibility (75.4%) and perceived benefit
      (55.6%). Mass media was the main source of their information regarding influenza
      A. CONCLUSION: Considering the findings of this study and the relation between
      HBM components and the preventive behaviors of students, it seems that using HBM
      could be useful in improving preventive behaviors of influenza A among the
      studied population.

PMID- 24083274
TI  - The effect of family-based intervention on empowerment of the elders.
AB  - BACKGROUND AND OBJECTIVE: Adult age is a sensitive period of human life and
      paying attention to the issues and needs of this stage is a social necessity.
      Regarding the specific needs of this period, considering the empowerment,
      dignity, and self-efficacy in the elders is very important too, which is
      frequently neglected. This study aims to determine the effect of family-based
      interventions on the elders' empowerment with emphasis on self-efficacy, self
      esteem, perceive threat, and quality of life of the elders in Isfahan. MATERIALS
      AND METHODS: In this semi-experimental study, 64 elderly people with the ability
      to perform routine and daily tasks without dependence on others and without
      systemic and restrictive diseases were chosen by available sampling method and
      were divided into two intervention and control groups. In intervention group, the
      model of family-based empowerment was trained and conducted in ten 45-minute
      sessions. The level of perceived threat, self-esteem, self-efficacy, and life
      quality in both groups were evaluated before and after intervention through a
      questionnaire. Chi Square, paired and independent t-test were used for
      statistical analysis. RESULTS: Statistical test of paired t-test indicated that
      family-based empowerment model significantly increased the quality of life in
      intervention group compared with the control group (P < 0.01). Statistical test
      of independent t-test showed a significant difference in intervention and control
      groups after conducting the program in the score of the self-esteem (P < 0.001).
      Regarding self-efficiency, independent t-test did not show any significant
      difference between the two groups before intervention. Despite the increase of
      self-efficacy score after intervention, this difference was not significant (P =
      0.076). CONCLUSION: Regarding the findings of this research, we can conclude that
      it is possible to increase the level of self-efficacy, self-esteem, perceived
      threat, and finally quality of life of the elders and facilitate the way for
      healthy aging and being healthy in this period using family-based empowerment
      model regularly and consistently.

PMID- 24083275
TI  - Knowledge and attitude toward menopause phenomenon among women aged 40-45 years.
AB  - BACKGROUND: Appropriate understanding of women that certain physical, mental,
      social and psychological changes occur during menopause helps them with greater
      readiness to cope with these changes. In all training programs to identify and
      analyze perceptions of the subjects is a key component. The purpose of this study
      was to investigate the knowledge and attitude of women toward the menopause
      phenomenon. MATERIALS AND METHODS: This cross-sectional study was conducted on
      400 healthy and non-menopaused women aged 40-45 years. The stratified sampling
      method was used and participation in this study was based on obtaining informed
      consent. The data collection instrument was a questionnaire consisting of three
      parts: demographic information, questions to assess knowledge and attitude
      investigation questions. FINDINGS: The results showed that the average knowledge
      score of subjects was 63.57 +/- 10.79, and their average attitude score was 61.21
      +/- 12.73. In this study, 8% of the subjects had poor knowledge, 68% had moderate
      knowledge and 38.5% had good knowledge. Meanwhile, 81.5% of the women had a
      positive attitude toward menopause. The correlation test showed that knowledge
      and attitude are meaningfully related to economic status and education level.
      But, the relationship between knowledge and attitudes of women under study was
      not significant. CONCLUSION: Identifying the quality of women's subjective
      perception of menopause has an essential role in the development of accurate and
      appropriate programs to promote women's health during menopausal years.

PMID- 24083276
TI  - The effect of educational program on knowledge, attitude and practice of mothers
      regarding prevention of febrile seizure in children.
AB  - BACKGROUND: Febrile convulsion is one of the most common problems in children
      aged 5 months to 6 years. The aim of this study was to explore the effectiveness
      of an educational program on mothers for prevention of febrile seizure in
      children. MATERIALS AND METHODS: In this clinical trial study, 88 mothers were
      chosen who were divided into intervention and control groups, randomly. Data of
      the control and intervention groups were collected in two stages, before
      intervention and 1 month after intervention, by a validated and reliable
      questionnaire. The intervention consisted of three educational sessions, each one
      lasting for 60 min. Data were analyzed using chi-square, t-test and paired t
      test. FINDINGS: Age average of subjects in the intervention group and in the
      control group was 26.75 and 26.84 years, respectively. The results showed a
      significant increase in the knowledge (P < 0.001), attitude (P = 0.04) and
      practice (P = 0.01) in the intervention group 1 month after intervention compared
      with that before intervention, while such an increase was not seen in the control
      group. CONCLUSION: This study confirmed the efficiency of educational
      interventions in improving mother's knowledge, attitude and practice regarding
      prevention of febrile seizure in children.

PMID- 24083277
TI  - Nutritional status of adolescents in Bangladesh: Comparison of severe thinness
      status of a low-income family's adolescents between urban and rural Bangladesh.
AB  - INTRODUCTION: This study estimated the nutritional as well as the severe thinness
      status (according to the World Health Organization [WHO]) of a low-income
      family's adolescent girl and also their early age of life in both urban and rural
      adolescent girls in Bangladesh. MATERIALS AND METHODS: This cross-sectional study
      measured the height, weight and muac by standard procedure for calculating the
      body mass index according to the WHO reference. A 2-days, 24-h food recall and
      food frequency questionnaire was used to estimate the food frequency, energy
      intake, protein and carbohydrate. A multistage, multiphase stratified cluster
      sampling was used to select the study population from two locations in
      Bangladesh: Dhaka city and the east region of Trishal (district of Mymensingh).
      The study subjects were low-income families' adolescent girls (n = 214) aged 14
      17 years. The two groups contained an equal number of respondents (n=107/group).
      RESULTS: Results revealed that economic status had a significant effect on
      nutritional status. Nutritional status of low-income families' adolescent were
      low both in urban and rural adolescents, but severe thinness rate according to
      the WHO of urban (22.4%) adolescents was much higher than rural (10.3%)
      adolescents (chi-square = 4.9 and P-value = 0.01), and was also higher at an
      earlier age of their life. In food intake distribution and food consumption
      status, the same results were seen. The percentage of never eat meat and fish of
      low-income families adolescent girls were (29.7%, 11.4%) in urban group and
      (24.4%, 6.8%) in rural group. The main food rice consumption of urban adolescents
      was also about half that of rural adolescents per day. The study also shows that
      intake of energy, protein, carbohydrate and fat were significantly different
      between urban and rural girls. Only 53% energy was covered of the recommended
      daily energy intake in urban adolescents. CONCLUSION: Based on the food recall
      and anthropometric results, we conclude that malnutrition is common in low-income
      family's adolescents, and the severe thinness rate is much higher in urban than
      in rural adolescents, as also their early age of life in both low-income family's
      adolescents girls in Bangladesh.

PMID- 24083278
TI  - Use of interactive teaching methods in tobacco cessation program and examine it
      by using objective structured clinical exam.
AB  - BACKGROUND: Tobacco addiction is an important public health issue. It is
      important for health professional to counsel the tobacco users for cessation.
      AIM: To enhance communication skills of MBBS (Bachelor of Medicine and Bachelor
      of Surgery) students in counseling of tobacco users by using interactive teaching
      methods and examine it by using OSCE. MATERIALS AND METHODS: It was a before and
      after comparison study. Communication skills of students were examined by
      standardized patients (investigators) by objective structured clinical
      examination (OSCE) method before and after intervention. All the students were
      trained to enhance the communication skills by role play, interactive session,
      anecdotes. Statistical analysis was done by using Paired t-test. RESULTS: The
      difference in scores at all the 3 stations before and after the intervention and
      also global scores before and after the intervention was statistically highly
      significant (P = 0.0001). CONCLUSION AND RECOMMENDATION: Communication skills of
      students in counseling tobacco users improved after they were given role play,
      interactive session, anecdotes. Similar model can be used to improve the
      communication/counseling skills in other important health hazards.

PMID- 24083279
TI  - Relationship between body satisfaction with self esteemand unhealthy body weight
      management.
AB  - INTRODUCTION: A favorable or unfavorable attitude about self was named self
      esteem. According to Maslow theory to achieve quality of life and happiness, one
      must reach the gradual fulfillment of human needs, including a high degree of own
      self-esteem. Body dissatisfaction is a negative distortion of one's body which is
      especially mentioned by the women. Many studies have shown links between self
      esteem, body dissatisfaction, health and behaviors. this study intends to
      determine relationship between body satisfaction, self esteem and unhealthy
      weight control behaviors between women. METHODS: This cross-sectional study was
      done on 408 women employees in Isfahan University and Isfahan University of
      Medical Sciences during 1390. They were chosen according to the stratified random
      sampling method. Inclusion criteria were 1) willing to participate in the study
      and 2) lack of serious physical defect 3) not being in pregnancy or breastfeeding
      course. Exclusion criteria was filling out questionnaires incompletely. Data
      collection tool was a multidimensional questionnaire which comprised of 4
      sections as following: demographic (5items), A self-administrative questionnaire
      for body Satisfaction (7 items), Rosenberg Self-Esteem Scale (10 items) and a
      standard Weight Control Behavior Scale (18 items). Cranach's alpha was 0.9 or
      higher for the different sections. Finally, collected data was analyzed with
      SPSS18 using the independent T-test, one-way ANOVA, Pearson correlation
      coefficient, regression, Spearman correlation. RESULTS: Frequencies of
      participants by weight category were 14.1% for obese, 35.3% for overweight, 47.6%
      for normal weight. The mean body satisfaction score in the studied women was
      63.26 +/- 16.27 (from 100). Mean score of self esteem was 76.70 +/- 10.45. 51.5%
      of women had medium self esteem, 47.5% had high self esteem. Pearson correlation
      showed that the variables of body Satisfaction (r = 0.3, P = 0.02), BMI (r = -
      0.14, P < 0.003), education level (r = 0.22, P < 0.001), income (r = 0.14, P <
      0.004), consumption of fruit (r = 0.13, P < 0.008) all correlated with self
      esteem significantly. Women with higher self esteem used higher fruits had a good
      nutrition overall (r = 0.11, P = 0.02). 92.15%, 10.8% of women respectively
      participated in one of healthy and unhealthy weight control behavior. There was
      not any Relationship between self esteem and healthy weight control behavior
      while finding showed reverse relationship between self esteem and Unhealthy
      Dieting Behaviors. CONCLUSION: It seemed women identity in our society tied to
      social appreciations that formed and supported by body satisfaction. When they
      feel their current appearance is differ from ideal appearance, they feel down and
      have lower self esteem and used unhealthy dieting behavior and low fruits daily.
      Due to importance of precise self evaluation, self esteem can be used to design
      and conduct public health programs, especially for women.

PMID- 24083280
TI  - Assessing knowledge of primary school teachers on specific learning disabilities
      in two schools in India.
AB  - BACKGROUND: Evaluation of fund of knowledge about SLD among kindergarten and
      primary school teachers is essential to avoid misdiagnosis of SLD and to plan for
      specific teacher education to enable early identification of SLD among children.
      AIM: To assess the knowledge of learning disability among primary school teachers
      in India and to investigate its psychometric properties. MATERIALS AND METHODS:
      An observational study was carried out 34 primary school teachers from 2
      different schools in Puducherry town agreed to participate in this study with
      informed consent. We used a multiple choice questionnaire format with a total of
      50 questions, 5 choices for each question and a total score of 50. The study was
      held at the schools where these teachers were employed using pen and paper
      testing method and data were entered into the computer for statistical analysis.
      STATISTICAL ANALYSIS: Total scores on the questionnaire of all teachers were
      calculated. Content validity, reliability coefficient, discrimination factor, and
      facility factor were analyzed using SPSS software. RESULTS: 29% of the questions
      were correctly answered by all 34 teachers. The mean total score for this sample
      was 14.50 +/- 9 and total item score for the 50 items was 9.90 +/- 4. Cronbach's
      (alpha) reliability was 0.89. Overall discrimination index was + 0.2 and facility
      factor analysis score was 0.26. CONCLUSIONS: Validation of this new screening
      questionnaire was successful in Indian setting. It has to be used in other
      settings to extrapolate our findings.

PMID- 24083281
TI  - Electronic health indicators in the selected countries: Are these indicators the
      best?
AB  - BACKGROUND: Many changes have been made in different sciences by developing and
      advancing information and communication technology in last two decades. E-health
      is a very broad term that includes many different activities related to the use
      of electronic devices, software as well as hardware in health organizations.
      AIMS: The aim of this study is comparing electronic health indicators in the
      selected countries and discussion on the best indicators. SETTINGS AND DESIGN:
      This study has chosen 12 countries randomly based on the regional division of the
      WHO. The relevant numbers of health indicators and general indicators and
      information technology indicators are extracted of these countries. We use data
      from the Bitarf's comparative study, which is conducted by the Iranian Supreme
      Council of Information Technology in 2007. MATERIALS AND METHODS: By using
      Pearson correlation test, the relations between health general indicators and IT
      indicators are studied. STATISTICAL ANALYSIS USED: Data was analyzed based on the
      research objectives using SPSS software and in accordance with research questions
      Pearson correlation test were used. RESULTS: The findings show that there is a
      positive relation between indicators related to IT and "Total per capita health,
      healthy life expectancy, percent literacy". Furthermore, there is a mutual
      relation between IT indicators and "mortality indicator". CONCLUSION: This study
      showed differences between selective indicators among different countries. The
      modern world, with its technological advances, is not powerless in the face of
      these geographic and health disparity challenges. Researchers must not rely on
      the available indicators. They must consider indicators like e-business
      companies, electronic data internet, medical supplies, health electronic record,
      health information system, etc., In future, continuous studies in this field, to
      provide the exact and regular reports of amount of using of these indicators
      through different countries must be necessary.

PMID- 24083282
TI  - Experiences of experts about the instances of plagiarism.
AB  - INTRODUCTION: Plagiarism is defined as intentional deceiving or lack of honesty,
      which deprives others from both material and spiritual possessions. Ethics is
      considered as one of the most important aspects of evaluating the quality of
      higher education. Moreover, scientific ethics should be reflected from university
      values, as a specialized institution, rather than being a reflection of the
      others cares. Therefore, the main aim of the present study is explore of expert
      experiences about plagiarism in Isfahan University of Medical Sciences. MATERIALS
      AND METHODS: This study employed qualitative method with using in-deep interview.
      The research participants consisted of 21, who tend to this work. Semi structure
      interview were conducted and recorded. The method of analyzing data was 'thematic
      analysis'. The data were transcribed and saved on computer after each interview.
      Themes and sub-themes were extracted. Finally, relevant sub-themes were arranged
      in a category and suggested were presented. RESULT: Analyzing data showed 600
      primary codes, 40 sub-themes and 6 themes. The main themes included repeated
      works, non-normative adoption, non-normative adaptation, shares distribution,
      forging, and profit-seeking, each of which consisted of one or several subgroups.
      CONCLUSION: The findings of this study show that since, there are numerous ways
      of cheating, the universities' research committees must create institutions in
      order to educate the individuals how to avoid plagiarism. In addition, providing
      information about different types of scientific violations, as well as their
      following punishments might lead to the decrease of such misbehaviors.

PMID- 24083283
TI  - Impact of school-based oral health education program on oral health of 12 and 15
      years old school children.
AB  - BACKGROUND: Health education for the school age child is a specialized field
      within the broad discipline of education. Oral health education program are
      educational aspects of any curative, preventive and promotional health activity.
      AIM: The study has been undertaken to evaluate the impact of oral health
      education on the status of plaque, gingival health and dental caries among 12 and
      15 years old children attending government school in Shimla city. MATERIALS AND
      METHODS: Two hundred and seventy six school children participated in the study.
      The study was conducted over a period of 4 months from May 2010 to August 2010 in
      Government Senior Secondary School, Sanjauli. Plaque, gingival and caries status
      was assessed by using Silness and Loe plaque index, Loe and Silness gingival
      index and WHO modified DMFT index, respectively. Data was analyzed using the
      software SPSS version 15. Paired t-test and Wilcoxon signed rank sum test were
      used appropriately for statistical comparisons. P value <=0.05 was considered
      statistically significant. RESULTS: Overall mean plaque score and gingival score
      decreased significantly after oral health education irrespective of gender.
      However, decrease in plaque score among 15 years old female children and gingival
      scores among 12 and 15 years old female subjects was not significant. Difference
      in mean caries status was statistically insignificant among all the subjects.
      CONCLUSION: Short term oral health education program may be useful in improving
      oral hygiene and gingival health. Coordinating efforts should be enhanced between
      school personnel, parents and health professionals to ensure long-term benefits
      of such program.

PMID- 24083284
TI  - The mental health and substance abuse among youths aged 18 to 29: A comparative
      study.
AB  - INTRODUCTION: Drug abuse, as a social phenomenon, is one of the health problems
      of the present era. Inclination to drug abuse like other social phenomena is
      complex and multi-causal. Emphasizing on the psychological factors, the present
      study attempts to compare the amount of depression, anxiety and stress between
      drug abusers and the comparison group. MATERIAL AND METHODS: The research method
      is descriptive-analytic and its design is comparative. The population includes
      the youths of ages of 18-29 (with and without drug abuse behavior). The sampling
      is random and the sample size in drug abuser group is 183 and in the comparison
      group, it is 207 persons. The data collection instrument is questionnaire of
      personal information containing 6 questions and the standard questionnaire is
      DASS-21. The data were analyzed through SPSS-18 and statistic tests independent
      T, chi square, Mann-Whitney, and logistic regression analysis. FINDINGS: The
      average age of the drug abusers is 25.9 +/- 2.96 years and the comparison group
      is 24.2 +/- 3.36. The most amount of methamphetamine is 75.9%. A significant
      correlation was observed between the education level and drug abuse behavior (P <
      0.001). The score of the stress, anxiety and stress in drug abusers is more than
      the comparison group and this relationship was significant (P < 0.001). Based on
      the logistic regression analysis results, anxiety has the highest correlation
      with drug abuse behavior. CONCLUSION: The low level of education is an effective
      factor in drug abuse. According to the strong correlation between psychological
      factors and drug abuse behavior, it is necessary to suggest social plans of
      prevention and treatment of mental disorders.

PMID- 24083285
TI  - The effect of ward round teaching on patients: The health team and the patients'
      perspectives.
AB  - INTRODUCTION: Holding bedside round teaching and involving patients in the
      teaching of the students might lead to patients' dissatisfaction. This study was
      carried out in order to find the viewpoints of the patients and the medical team
      about the effect of clinical round on patients hospitalized in Isfahan University
      of Medical Sciences. MATERIALS AND METHODS: This study is of cross-sectional
      descriptive type which is carried out in Isfahan University of Medical Sciences
      using researcher-made tools. The statistical population included the hospitalized
      patients, interns, residents, and nurses of the internal wards of educational
      hospitals. In this study, 110 patients and 150 health team staff are
      participated. The analysis of the data was done through software Statistical
      Package for Social Science (SPSS) 11.5 and descriptive and inferential statistics
      were applied. Statistical analysis of the variance did not show any significant
      difference among the interns', nurses', and residents' perception of patient's
      satisfaction. RESULTS: Generally, the patients had a positive viewpoint toward
      things happening during a round, whereas the medical team's viewpoint was
      negative. In both groups, the highest satisfaction average pertained to the
      number of times and the duration of visits, but both groups believed that lack of
      a definite responsible medical doctor, feeling of insecurity during the
      incongruous and unclear discussions, and the level of respect for the patient
      were the causes of dissatisfaction with the clinical round process. CONCLUSION:
      The current method of clinical rounds can result in patients' dissatisfaction. On
      the other hand, proper relationship with them leads to the development of a more
      positive attitude in them. Therefore, revision and correction of the current
      clinical round procedures and teaching the communication skills to the medical
      team could help improve this process.

PMID- 24083286
TI  - Review the key role of self-efficacy in diabetes care.
AB  - INTRODUCTION AND AIMS: Diabetes is one of the chronic and prevalent diseases in
      the world. Diabetic patients' number has increased 7 times during last 20 years.
      If this current situation continues, diabetic patients' population will be 350
      millions ones in 2030. It means that 7 millions people will be added annually. Up
      to now, different uncontrollable factors have been monitored in self-caring of
      this disease for managing and preventing from its early and late side effects.
      This research is conducted to study the role of self-efficacy as a determinant
      agent in self-caring of diabetic patients. STUDY METHOD: This is a narrative
      review study in which various information banks and search motors such as PubMed,
      ProQuest, SCOPUS, Elsevier were reviewed. Diabetes, self-care and self efficacy
      keywords from cross sectional, cohort, clinical experimental studies and
      systematic review were also used in the study construction. Iranian Banks such as
      IRANMEDEX, MEDLINE and also different articles from domestic research and
      scientific magazines were selected. Time spectrum of reviewed studies was
      supposed to be published from 1990 up to 2011. RESULTS: Self-care situation among
      diabetic patients not only is unsatisfactory but also the studies' results show
      that self-efficacy rate is low among them. The findings of the studies prove that
      there is a direct relation between self-efficacy and self-care in the patients in
      a way that this construct owns the predictability power of self-care behavior.
      CONCLUSION: Self-caring has a significant role in controlling of diabetes
      disease. Self-efficacy can induce motivation directly take health promoting
      behavior through efficacy expectations. It also affects motivation, indirectly,
      through perceived barriers and determining commitment or stability for following
      function map. So, self-efficacy is very important in changing self-care behavior
      process.

PMID- 24083288
TI  - Teaching legacy: Future perspectives.

PMID- 24083287
TI  - Structural role of perceived benefits and barriers to self-care in patients with
      diabetes.
AB  - INTRODUCTION AND GOAL: In diseases and disorders such as diabetes, treatment and
      disease management depends mostly on patient's performance. So, self-care is very
      important in these patients and they can affect their own welfare, functional
      capabilities, and disease processes by achieving self-care skills. Nowadays, we
      know that self care follows individual, psychological and social factors which
      its recognition can assist health care providing systems to carry out educational
      programs. This study aimed to investigate the role of perceived benefits and
      barriers in doing self-care behaviors among diabetic patients. MATERIALS AND
      METHODS: This study is a narrative review and articles with sectional, cohort,
      and interventional, clinical trial, qualitative and narrative designs were chosen
      using databases and academic search engines such as PubMed, SCOPUS, ProQuest,
      Elsevier and key words like self-care diabetes, perceived benefits and barriers.
      Persian articles were also selected using databases like IRANMEDEX, MEDLIB, as
      well as searching the articles in sites of domestic scientific magazines.
      RESULTS: Reviewed articles' findings show the average situation of perceived
      benefits and barriers in diabetic patients regarding self-care. Qualified blood
      sugar (glucose) control, weight control, happiness feeling and expenses reduction
      are the most important perceived benefits. The most significant perceived
      barriers in self-care consist of lack of family support, shame feeling,
      forgetfulness and not being able to ignore foods' flavor. CONCLUSION: Perceived
      benefits and barriers, as central constructs in some patterns and theories of
      behavior change, were related to self-care, so that it was directly related to
      perceived benefits and reversely related to perceived barriers. Therefore, these
      two constructs can be considered as strategies for promoting self-care behaviors
      in diabetic patients.

PMID- 24083289
TI  - Understanding the relationship between nutritional knowledge, self-efficacy, and
      self-concept of high-school students suffering from overweight.
AB  - BACKGROUND AND AIM: Adolescents' overweight problems have been paid much
      attention due to their significant increase in recent decades in developed
      countries. Poor eating patterns subsequently affect their self-efficacy and self
      concept. Therefore, paying attention to the nutritional knowledge of overweight
      students in this period is essential. This study examines the relationship
      between self-efficacy, self-concept, and nutritional knowledge of overweight
      students in the city of Isfahan. MATERIALS AND METHODS: The 140 overweight
      students who participated in this descriptive, analytical study with were
      randomly selected from one of five areas of Isfahan city in the year 2011-2012.
      Questionnaires for data collection in this study included demographic form,
      nutrition knowledge, Cooper Smith self-esteem, and general self-efficacy
      questionnaire. Data were analyzed by ANOVA, regression, and Pearson's correlation
      coefficient with statistical package in social sciences version 18. RESULTS:
      There was a significant correlation between whole nutritional knowledge and self
      efficacy (r = 0.29, P > 0.001) and self-concept (r = 0.26, P = 0.002). There was
      a significant correlation between self-efficacy and self-concept (r = 0.3, P =
      0.001). Furthermore, in the selection of food section there was no significant
      correlation with the self-concept (r = 0.147, P = 0.083). Regression analysis
      between self-concept, self-efficacy, family dimension, father's education,
      mother's education, father's occupation, mother's occupationa and income with
      nutrition knowledge showed that these eight variables explain 17.7% of the
      variance in health behaviors totally. CONCLUSION: By conducting this study, and
      revealing the direct relationship between nutritional knowledge, self-concept,
      and self-efficacy, we could conclude that if nutritional knowledge of overweight
      students is promoted, this factor would lead to an increase their self-concept
      and self-efficacy in order to adopt healthy behaviors and have the expected
      healthy eating and healthy life-style.

PMID- 24083290
TI  - The relationship between emotional intelligence and academic stress in students
      of medical sciences.
AB  - BACKGROUND AND AIM: Emotional intelligence (EI) theory provides a view about
      predicting effective factors in people's lives whether in education or
      profession. According to earlier studies, people who have higher emotional skills
      are more successful in many of life aspects :e.g., reaction to stress and
      controlling stress situations. Since students are the future of society, this
      study was carried out to evaluate the relationship between EI and education
      stress in the students of Birjand University of Medical Sciences (BUMS).
      MATERIALS AND METHODS: In this cross-sectional study, 260 students were selected
      by proportional sampling in four faculties: Medicine, Nursing and Midwifery,
      Paramedical Sciences, and Health. Data were collected using two questionnaires:
      The standardized EI Shering's (33 questions, five domains) and the Student-Life
      Stress Inventory (57 questions, nine domains). The obtained data were analyzed by
      independent t-test, Pearson's correlation coefficient, and linear regression at
      the significant level of alpha = 0.05. RESULTS: Totally, 65.8% of participants
      were females and 31.1% were males. The educational level of the participants
      included Associate's degree (44.6%) Bachelor's degree in science (31.2%), and
      medical science (23.1%). There was no significant correlation between EI scores
      and educational stress in students. But there was a significant relationship
      between EI with sex (P = 0.02) and mean of EI scores with three domains of
      academic stress: Personal favorites (P = 0.004), reaction to stressors (P =
      0.002), and performance in stressful situations (P = 0.001). CONCLUSION: Although
      EI growth in different individuals can promote their success, it cannot decrease
      academic stress by itself which was particularly significant in females.
      Therefore, other causes of stress such as individual differences must be taken
      into consideration.

PMID- 24083301
TI  - Establishing a normal range for induced sputum cell counts in Western Canada.
AB  - BACKGROUND: Induced sputum cell counts are a noninvasive, reliable method for
      evaluating the presence, type and degree of airway inflammation. Whether current
      reference values for induced sputum cell counts are applicable in other induced
      sputum laboratories, particularly those in Western Canada or at elevated
      altitude, is not clear. OBJECTIVES: To describe the normal range of induced
      sputum cell counts in healthy adults in Western Canada. METHODS: A total of 105
      healthy nonsmoking adults with normal bronchial responsiveness and no history of
      lung disease proceeded with sputum induction. Sputum samples were fixed in
      formalin. RESULTS: Sixty-nine subjects were included in the final analyses. The
      mean +/- SD and median (interquartile range) of the cell counts, respectively,
      were: total cell count 2.453 +/- 2.108, 2.000 (2.512); neutrophils 1.212 +/-
      1.491, 0.721 (1.016); eosinophils 0.034 +/- 0.069, 0.005 (0.043); macrophages
      1.050 +/- 1.213, 0.696 (1.005); lymphocytes 0.057 +/- 0.161, 0.001 (0.049); and
      bronchial epithelial cells 0.041 +/- 0.126, 0.000 (0.027). The respective
      differential cell percentages were: neutrophils 50.3 +/- 23.5, 51.9 (32);
      eosinophils 1.4 +/- 2.3, 0.3 (2); macrophages 43 +/- 22.8, 39.3 (32); lymphocytes
      2.6 +/- 5.2, 0.4 (2.5); and bronchial epithelial cells 2.2 +/- 4.8, 0.0 (2.9).
      Bland-Altman analysis and intraclass correlation coefficients revealed excellent
      interobserver agreement for measurement of sputum cell types. DISCUSSION: The
      range of induced sputum cell counts performed in a laboratory in Western Canada
      in healthy nonsmoking adult subjects was described; cellular distributions were
      similar to previous studies. This was also the first description of normal values
      for formalin-fixed induced sputum samples. CONCLUSIONS: These results confirm
      that current reference values for induced sputum are generalizable across
      different laboratories, including those in Western Canada and those at elevated
      altitude, and are also generalizable to formalin-fixed samples, allowing use in
      the broader Canadian asthma population.

PMID- 24083302
TI  - Prediction scores do not correlate with clinically adjudicated categories of
      pulmonary embolism in critically ill patients.
AB  - BACKGROUND: Prediction scores for pretest probability of pulmonary embolism (PE)
      validated in outpatient settings are occasionally used in the intensive care unit
      (ICU). OBJECTIVE: To evaluate the correlation of Geneva and Wells scores with
      adjudicated categories of PE in ICU patients. METHODS: In a randomized trial of
      thromboprophylaxis, patients with suspected PE were adjudicated as possible,
      probable or definite PE. Data were then retrospectively abstracted for the Geneva
      Diagnostic PE score, Wells, Modified Wells and Simplified Wells Diagnostic
      scores. The chance-corrected agreement between adjudicated categories and each
      score was calculated. ANOVA was used to compare values across the three
      adjudicated PE categories. RESULTS: Among 70 patients with suspected PE,
      agreement was poor between adjudicated categories and Geneva pretest
      probabilities (kappa=0.01 [95% CI -0.0643 to 0.0941]) or Wells pretest
      probabilities (kappa=-0.03 [95% CI -0.1462 to 0.0914]). Among four possible, 16
      probable and 50 definite PEs, there were no significant differences in Geneva
      scores (possible = 4.0, probable = 4.7, definite = 4.5; P=0.90), Wells scores
      (possible = 2.8, probable = 4.9, definite = 4.1; P=0.37), Modified Wells
      (possible = 2.0, probable = 3.4, definite = 2.9; P=0.34) or Simplified Wells
      (possible = 1.8, probable = 2.8, definite = 2.4; P=0.30). CONCLUSIONS: Pretest
      probability scores developed outside the ICU do not correlate with adjudicated PE
      categories in critically ill patients. Research is needed to develop prediction
      scores for this population.

PMID- 24083304
TI  - The European Society of Cardiology Cardiologists of Tomorrow initiative: building
      the cardiology youth for the future.

PMID- 24083303
TI  - The utility of a portable sleep monitor to diagnose sleep-disordered breathing in
      a pediatric population.
AB  - BACKGROUND: Central and/or obstructive sleep-disordered breathing (SDB) in
      children represents a spectrum of abnormal breathing during sleep. SDB is
      diagnosed using the gold standard, overnight polysomnography (PSG). The limited
      availability and access to PSG prevents its widespread use, resulting in
      significant delays in diagnosis and treatment of SDB. As such, portable sleep
      monitors are urgently needed. OBJECTIVE: To evaluate the utility of a
      commercially available portable sleep study monitor (PSS-AL) (ApneaLink, ResMed,
      USA) to diagnose SDB in children. METHODS: Children referred to a pediatric sleep
      facility were simultaneously monitored using the PSS-AL monitor and overnight
      PSG. The apnea-hypopnea index (AHI) was calculated using the manual and
      autoscoring function of the PSS-AL, and PSG. Sensitivity and specificity were
      compared with the manually scored PSS-AL and PSG. Pearson correlations and Bland
      Altman plots were constructed. RESULTS: Thirty-five children (13 female)
      completed the study. The median age was 11.0 years and the median body mass index
      z-score was 0.67 (range -2.3 to 3.8). SDB was diagnosed in 17 of 35 (49%)
      subjects using PSG. The AHI obtained by manually scored PSS-AL strongly
      correlated with the AHI obtained using PSG (r=0.89; P<0.001). Using the manually
      scored PSS-AL, a cut-off of AHI of >5 events/h had a sensitivity of 94% and a
      specificity of 61% to detect any SDB diagnosed by PSG. CONCLUSIONS: Although PSG
      is still recommended for the diagnosis of SDB, the ApneaLink sleep monitor has a
      role for triaging children referred for evaluation of SDB, but has limited
      ability to determine the nature of the SDB.

PMID- 24083305
TI  - The Lotus valve for transcatheter aortic valve implantation.
AB  - The Lotus valve, a second-generation transcatheter aortic valve implantation
      device, shows good performance in REPRISE II.

PMID- 24083306
TI  - The Swedish Society of Cardiology.
AB  - Dr David Erlinge, the Society President, outlines the history and present-day
      activities of the Society.

PMID- 24083307
TI  - UK implements national programme for surgical trials.

PMID- 24083308
TI  - Rheumatic heart disease back in the limelight.

PMID- 24083309
TI  - Mary Amanda Dixon Jones: woman surgeon in a man's world.

PMID- 24083310
TI  - Joseph Lister's domestic science.

PMID- 24083311
TI  - Hemoptysis caused by a left subclavian pseudoaneurysm: endovascular solution for
      a challenging case.
AB  - This is one of the first reports of a left subclavian pseudoaneurysm in a patient
      presenting with massive hemoptysis. We present a challenging case of a patient
      who consulted for hemoptysis. Imaging revealed a left subclavian artery
      pseudoaneurysm that caused a pulmonary parenchymal lesion. Treatment with a self
      expanding thoracic stent-graft and a subclavian occluder was successful.

PMID- 24083312
TI  - Voluntary guidelines for emergency physicians: clarifying New York city's efforts
      to curb opioid misuse.

PMID- 24083313
TI  - Some research wants to be free, some follows the money: bogus journals complicate
      the open access movement.

PMID- 24083314
TI  - One seven hour observation in a hospital ward.

PMID- 24083315
TI  - Error analysis of stochastic gradient descent ranking.
AB  - Ranking is always an important task in machine learning and information
      retrieval, e.g., collaborative filtering, recommender systems, drug discovery,
      etc. A kernel-based stochastic gradient descent algorithm with the least squares
      loss is proposed for ranking in this paper. The implementation of this algorithm
      is simple, and an expression of the solution is derived via a sampling operator
      and an integral operator. An explicit convergence rate for leaning a ranking
      function is given in terms of the suitable choices of the step size and the
      regularization parameter. The analysis technique used here is capacity
      independent and is novel in error analysis of ranking learning. Experimental
      results on real-world data have shown the effectiveness of the proposed algorithm
      in ranking tasks, which verifies the theoretical analysis in ranking error.

PMID- 24083316
TI  - Retraction.

PMID- 24083317
TI  - Selected birth defects data from population-based birth defects surveillance
      programs in the United States, 2005-2009: Featuring critical congenital heart
      defects targeted for pulse oximetry screening.

PMID- 24083318
TI  - Improved transfer quality of CVD-grown graphene by ultrasonic processing of
      target substrates: applications for ultra-fast laser photonics.
AB  - In this paper, we experimentally found that the transfer quality of CVD-grown
      graphene could be improved by ultrasonic processing (UP) of target substrates
      thanks to the improved hydrophilicity. Atomic force micrograph and Raman
      spectroscopy revealed that the graphene films transferred onto the target
      substrate with UP possess less wrinkles and defects than that of the sample
      without UP. The improvement technique endows graphene more suitable for photonics
      applications because of its weaker optical loss, higher optical damage threshold
      and longer stability. By integrating a fiber pigtailed graphene (treated by UP)
      device into a fiber laser cavity, we could obtain narrower mode-locked pulse with
      higher optical-to-optical conversion efficiency and better optical spectral
      profile, in contrast with that without UP, which further verify the improved
      transfer quality of graphene by the UP technique. We anticipate that this
      transfer technique may be applicable to boost the performance of other graphene
      photonics devices, such as optical modulator, detector, polarizer, etc. 

PMID- 24083320
TI  - Photothermal infrared spectroscopy of airborne samples with mechanical string
      resonators.
AB  - Micromechanical photothermal infrared spectroscopy is a promising technique,
      where absorption-related heating is detected by frequency detuning of microstring
      resonators. We present photothermal infrared spectroscopy with mechanical string
      resonators providing rapid identification of femtogram-scale airborne samples.
      Airborne sample material is directly collected on the microstring with an
      efficient nondiffusion limited sampling method based on inertial impaction.
      Resonance frequency shifts, proportional to the absorbed heat in the microstring,
      are recorded as monochromatic IR light is scanned over the mid-infrared range. As
      a proof-of-concept, we sample and analyze polyvinylpyrrolidone (PVP) and the IR
      spectrum measured by photothermal spectroscopy matches the reference IR spectrum
      measured by an FTIR spectrometer. We further identify the organic surface coating
      of airborne TiO2 nanoparticles with a total mass of 4 pg. With an estimated
      detection limit of 44 fg, the presented sensor demonstrates a new paradigm in
      ultrasensitive vibrational spectroscopy for identification of airborne species. 

PMID- 24083319
TI  - Identification of palmitoyl protein thioesterase 1 in human THP1 monocytes and
      macrophages and characterization of unique biochemical activities for this
      enzyme.
AB  - The profiles of serine hydrolases in human and mouse macrophages are similar yet
      different. For instance, human macrophages express high levels of
      carboxylesterase 1 (CES1), whereas mouse macrophages have minimal amounts of the
      orthologous murine CES1. On the other hand, macrophages from both species exhibit
      limited expression of the canonical 2-arachidonoylglycerol (2-AG) hydrolytic
      enzyme, MAGL. Our previous study showed CES1 was partly responsible for the
      hydrolysis of 2-AG (50%) and prostaglandin glyceryl esters (PG-Gs) (80-95%) in
      human THP1 monocytes and macrophages. However, MAGL and other endocannabinoid
      hydrolases, FAAH, ABHD6, and ABHD12, did not have a role because of limited
      expression or no expression. Thus, another enzyme was hypothesized to be
      responsible for the remaining 2-AG hydrolysis activity following chemical
      inhibition and immunodepletion of CES1 (previous study) or CES1 gene knockdown
      (this study). Here we identified two candidate serine hydrolases in THP1 cell
      lysates by activity-based protein profiling (ABPP)-MUDPIT and Western blotting:
      cathepsin G and palmitoyl protein thioesterase 1 (PPT1). Both proteins exhibited
      electrophoretic properties similar to those of a serine hydrolase in THP1 cells
      detected by gel-based ABPP at 31-32 kDa; however, only PPT1 exhibited lipolytic
      activity and hydrolyzed 2-AG in vitro. Interestingly, PPT1 was strongly expressed
      in THP1 cells but was significantly less reactive than cathepsin G toward the
      activity-based probe, fluorophosphonate-biotin. KIAA1363, another serine
      hydrolase, was also identified in THP1 cells but did not have significant
      lipolytic activity. On the basis of chemoproteomic profiling, immunodepletion
      studies, and chemical inhibitor profiles, we estimated that PPT1 contributed 32
      40% of 2-AG hydrolysis activity in the THP1 cell line. In addition, pure
      recombinant PPT1 catalyzed the hydrolysis of 2-AG, PGE2-G, and PGF2alpha-G,
      although the catalytic efficiency of hydrolysis of 2-AG by PPT1 was ~10-fold
      lower than that of CES1. PPT1 was also insensitive to several chemical inhibitors
      that potently inhibit CES1, such as organophosphate poisons and JZL184. This is
      the first report to document the expression of PPT1 in a human monocyte and
      macrophage cell line and to show PPT1 can hydrolyze the natural substrates 2-AG
      and PG-Gs. These findings suggest that PPT1 may participate in endocannabinoid
      metabolism within specific cellular contexts and highlights the functional
      redundancy often exhibited by enzymes involved in lipid metabolism.

PMID- 24083321
TI  - Development and implementation of an electronic asthma record for primary care:
      integrating guidelines into practice.
AB  - RATIONALE: Evidence-based practice may be enhanced by integrating knowledge
      translation tools into electronic medical records (EMRs). We examined the
      feasibility of incorporating an evidence-based asthma care map (ACM) into Primary
      Care (PC) EMRs, and reporting on performance indicators. METHODS: Clinicians and
      information technology experts selected 69 clinical and administrative variables
      from the ACM template. Four Ontario PC sites using EMRs were recruited to the
      study. Certified Asthma Educators used the electronic ACM for patient assessment
      and management. De-identified data from consecutive asthma patients were
      automatically transmitted to a secure central server for analysis. RESULTS: Of
      the four sites recruited, two sites using "stand-alone" EMR systems were able to
      incorporate the selected ACM variables into an electronic format and participate
      in the pilot. Data were received on 161 visits by 130 patients aged 36.5 +/- 26.9
      (mean +/- SD) (range 2-93) years. Ninety-four percent (65/69) of the selected ACM
      variables could be analyzed. Reporting capabilities included: individual patient,
      individual site and aggregate reports. Reports illustrated the ability to measure
      performance (e.g. number of patients in control, proportion of asthma diagnoses
      confirmed by an objective measure of lung function), benchmark and use EMR data
      for disease surveillance (e.g. number of smokers and the individuals with
      suspected work-related asthma). CONCLUSIONS: Integration of this evidence-based
      ACM into different EMRs was successful and permitted patient outcomes monitoring.
      Standardized data definitions and terminology are essential in order for EMR data
      to be used for performance measurement, benchmarking and disease surveillance.

PMID- 24083322
TI  - Methylparaben isolated in solid argon: structural characterization and UV-induced
      conversion into methylparaben radical and isomeric ketenes.
AB  - Methylparaben (methyl p-hydroxybenzoic acid; MP) is a widely used antimicrobial
      preservative, being the most frequently used antimicrobial preservative in
      cosmetics. The generalized use of MP has become controversial, with several
      recent reports of dangerous side effects. For example, the presence of MP in
      human breast tumors and its harmful effects on human skin exposed to the sunlight
      have been demonstrated. In spite of the important practical relevance of the
      compound and of the controversy about its practical use, its structural and
      photochemical characterization had not been undertaken hitherto. To fill this
      gap, in the present study, MP was isolated in solid argon (T = 15 K) and
      structurally characterized by a combined infrared spectroscopy/quantum chemistry
      approach. The potential energy surface (PES) of the molecule was investigated in
      detail, revealing the existence of two almost isoenergetic (DeltaE(0) = 0.37 kJ
      mol(-1)) s-cis carboxylic ester low-energy conformers, with an estimated
      population ratio in the gas phase at room temperature (~298 K) of ca. 0.83. The
      calculations also predicted the existence of two high-energy (DeltaE(0) = ~50 kJ
      mol(-1)) s-trans carboxylic ester conformers of MP. Upon isolation of the
      compound in an argon matrix, only the lowest energy conformer was found to
      survive, due to occurrence of extensive conformational cooling during matrix
      deposition. The infrared spectrum of this conformer was obtained and interpreted.
      In addition, the chemical processes resulting from in situ irradiation of the
      matrix-isolated MP with a broadband UV source (lambda > 234 nm) were
      investigated, revealing extensive conversion of MP into highly reactive
      methylparaben radical and isomeric ketenes. These observations support the recent
      concerns regarding uses of MP, in particular when the compound has to be exposed
      to UV light. 

PMID- 24083323
TI  - Phomentrioloxin, a fungal phytotoxin with potential herbicidal activity, and its
      derivatives: a structure-activity relationship study.
AB  - Phomentrioloxin is a phytotoxic geranylcyclohexenetriol produced in liquid
      culture by Phomopsis sp. (teleomorph: Diaporthe gulyae), a potential
      mycoherbicide proposed for the control of the annual weed Carthamus lanatus. In
      this study, seven derivatives obtained by chemical modifications of the toxin
      were assayed for phytotoxic, antimicrobial, and zootoxic activities, and the
      structure-activity relationships were examined. Each compound was tested on
      nonhost weedy and agrarian plants, fungi, Gram+ and Gram- bacteria, and on brine
      shrimp larvae. The results provide insights into an investigation of the
      structural requirements for activity. The hydroxy groups at C-2 and C-4 appeared
      to be important features for the phytotoxicity, as well as an unchanged
      cyclohexentriol ring. A role seemed also to be played by the unsaturations of the
      geranyl side chain. These findings could be useful for understanding the
      mechanisms of action of new natural products, for identifying the active sites,
      and possibly in devising new herbicides of natural origin. 

PMID- 24083324
TI  - Adipocytic cells augment the support of primitive hematopoietic cells in vitro
      but have no effect in the bone marrow niche under homeostatic conditions.
AB  - Mesenchymal stem cells (MSCs), as well as osteoblastic cells derived from these
      MSCs, have been shown to be key components of the hematopoietic stem cell (HSC)
      niche. In this study, we wished to examine whether other cell types that are
      known to differentiate from MSCs similarly regulate the stem cell niche, namely
      cells of the adipocyte lineage. Recent studies have examined the role that
      adipocytes play in the biology of the HSCs in different bone locations and in
      transplantation settings; however, none have examined their role under
      homeostatic conditions. We compared the ability of adipocytic and nonadipocytic
      cell lines to support primitive hematopoietic cells in vitro. Preadipocytic cell
      lines demonstrated enhanced support of hematopoietic cells. Similarly, primary
      bone marrow (BM) cells treated with troglitazone, a drug that enhances
      adipogenesis, also demonstrated augmented support over control-treated stromal
      cells. We further examined the effects of increased adipocyte number in vivo
      under homeostatic conditions using troglitazone treatment and found that these
      alterations had no effect on HSC frequency. Taken together, we demonstrate that
      cells of the adipocyte lineage promote the ability of stromal cells to support
      primitive hematopoietic cells in vitro, yet alterations of adipocyte number and
      volume in vivo have no effect. These data suggest that adipocytes are not a
      component of the adult BM HSC niche under homeostatic conditions.

PMID- 24083326
TI  - Modified-release capsules containing sodium riboflavin 5'-phosphate.
AB  - INTRODUCTION: The focus of this work was to produce delayed-release capsules
      containing riboflavin (vitamin B2, as API) layered pellets. Riboflavin therapy is
      indicated in patients with a riboflavin deficiency, which usually occurs in
      conjunction with malabsorption, alcoholism or a protein-calorie deficiency and
      rarely as the sole vitamin deficiency. Riboflavin is readily absorbed from the
      upper gastrointestinal tract by a specific transport mechanism. The dissolution
      rate of coated capsules was controlled through the coating of the capsules and
      the thickness of the coating layer. METHODS: The core pellets (Cellet 300) were
      loaded with a 10% aqueous solution of sodium riboflavin 5'-phosphate by a
      layering technique in a coating pan. Hard capsules were filled with riboflavin
      layered pellets and coated with Eudragit NE polymer with different coating layer
      thicknesses. The dissolution was tested in gastric and intestinal fluids with the
      half-change method. The dissolution profiles were analyzed with the use of
      different mathematical models and an attempt was made to predict the optimum
      coating film thickness that ensures the required degree and rate of dissolution.
      RESULTS: A new solid dosage form was developed which can enhance the
      bioavailability of riboflavin. RRSBW distribution and the Chapman-Richards growth
      function were used to fit the dissolution profiles. Statistical analysis
      indicated that the best products were described by the Chapman-Richards equation.
      The results were utilized to create a theoretical model suitable for prediction
      of the optimum film thickness that ensures the required release of riboflavin.

PMID- 24083327
TI  - Misuse of blood serum to assess exposure to bisphenol A and phthalates.

PMID- 24083328
TI  - Mild chronic kidney disease associated with greater risk of arterial stiffness in
      elderly adults.
AB  - OBJECTIVES: To assess the association between arterial stiffness and mild and
      moderate chronic kidney disease (CKD), independent of other cardiometabolic
      factors in an elderly population. DESIGN: Cross-sectional study. SETTING: Health
      examination data from National Cheng Kung University Hospital from 2006 to 2009.
      PARTICIPANTS: Eligible subjects aged 60 and older (N = 1,251). MEASUREMENTS: An
      average bilateral brachial-ankle pulse wave velocity (baPWV) of 1,400 cm/s or
      greater was defined as high baPWV. Based on the 2003 Clinical Practice Guidelines
      for Chronic Kidney Disease from the National Kidney Foundation, mild and moderate
      CKD were defined as CKD Stages 1 and 2 and Stages 3 to 5, respectively. RESULTS:
      Participants with a baPWV of 1,400 cm/s or greater (n = 1,028) had lower
      estimated glomerular filtration rates (eGFRs) but higher serum creatinine levels
      and greater prevalences of mild and moderate CKD, diabetes mellitus, prediabetes
      mellitus, hypertension, and prehypertension than those with baPWV less than 1,400
      cm/s (n = 223). In the multivariate analysis, mild (odds ratio (OR) = 2.58, 95%
      confidence interval (CI) = 1.02-6.54) and moderate (OR = 3.75, 95% CI = 1.02
      13.81) CKD were positively associated with greater baPWV (>=1,400 cm/s). Age,
      prediabetes mellitus, diabetes mellitus, prehypertension, and hypertension were
      also independently associated with greater baPWV. In the multiple linear
      analysis, moderate (beta = 120.45, P < .001) and mild CKD (beta = 69.90, P = .01)
      were positively associated with baPWV. There was also an independently inverse
      correlation between eGFR and baPWV (beta = -0.69, P = .04). CONCLUSION: Mild and
      moderate CKD increased the risk of greater arterial stiffness in elderly adults.
      Age, prediabetes mellitus, diabetes mellitus, prehypertension, and hypertension
      were also important correlates of increased arterial stiffness.

PMID- 24083329
TI  - Special issue: zoonoses.

PMID- 24083330
TI  - Organisational targets of patient safety improvement programs in primary care; an
      international web-based survey.
AB  - BACKGROUND: Organisational problems contribute to many errors in healthcare
      delivery. Our objective was to identify the most important organisational items
      in primary care which could be targeted by programs to improve patient safety.
      METHODS: A web-based survey was undertaken in an international panel of 65
      experts on patient safety from 20 countries. They were asked to rate 52 patient
      safety items on a five-point Likert scale which regards importance of each item
      for use for educational interventions to improve patient safety. RESULTS: The
      following 7 organizational items were regarded 'extremely important' by more than
      50% of the experts: the use of sterile equipment with small surgical procedures
      (63%), the availability of adequate emergency drugs in stock (60%), regular
      cleaning of facilities (59%), the use of sterile surgical gloves when recommended
      (57%), the availability of at least one adequately trained staff member to deal
      with collapse and need for resuscitation (56%), adequate information handover
      when a patient is discharged from the hospital (56%) and periodically training of
      GPs in basic life support and other medical emergencies (53%). CONCLUSION: Seven
      organisational items were consistently prioritized; other items may be relevant
      in specific countries only. The logical next step is to develop and evaluate
      interventions targeted at these items.

PMID- 24083332
TI  - Flexible ureterorenoscopy for lower pole stones: influence of the collecting
      system's anatomy.
AB  - BACKGROUND: The impact of renal anatomy on the success rate of flexible
      ureterorenoscopy (fURS) for lower pole stones is less clear than it is on shock
      wave lithotripsy, for which it is a recognized influence factor. We analyzed
      safety and efficiency of fURS using modern endoscopes for lower pole stones
      dependent on the collecting system's configuration. PATIENTS AND METHODS: We
      retrospectively evaluated a consecutive sample of 111 fURS for lower pole stones
      at our tertiary care center between January 2010 and September 2012 from our
      prospectively kept database. All procedures were performed with modern flexible
      ureterorenoscopes, nitinol baskets, holmium laser lithotripsy, and ureteral
      access sheaths whenever needed. The infundibular length (IL) and width (IW) and
      infundibulopelvic angle (IPA) were measured and the data were stratified for
      stone-free status and complications classified by the Clavien-Dindo scale.
      Univariate and multifactorial statistical analyses were performed. Correlation of
      operation time (OR-time) with anatomical parameters was conducted. RESULTS:
      Ninety-eight (88.3%) of the 111 patients were stone free after a single fURS. On
      multifactorial analysis, the stone size and IL had significant influence on the
      stone-free rate (SFR) (p<0.01), whereas IW did not. An acute IPA (<30 degrees )
      also had significant influence (p=0.01). The incidence of complications and OR
      time were not influenced by the pelvicaliceal anatomy. CONCLUSIONS: fURS is a
      safe and efficient treatment option for lower pole kidney stones. A long
      infundibulum and a very acute IPA (<30 degrees ) negatively affect the SFR.
      However, with second look procedures, a complete stone clearance is achievable
      even in case of unfavorable anatomic conditions. A narrow infundibulum has no
      negative effect while using modern endoscopes. The complication rate is not
      affected by the collecting system's anatomy.

PMID- 24083333
TI  - The burden of chronic diseases in a rural North Florida sample.
AB  - BACKGROUND: The degree of health disparities present in rural communities is of
      growing concern and is considered "urgent" since rural residents lag behind their
      urban counterparts in health status. Understanding the prevalence and type of
      chronic diseases in rural communities is often difficult since Americans living
      in rural areas are reportedly less likely to have access to quality health care,
      although there are some exceptions. Data suggest that rural residents are more
      likely to engage in higher levels of behavioral and health risk-taking than urban
      residents, and newer evidence suggests that there are differences in health risk
      behavior within rural subgroups. The objective of this report is to characterize
      the prevalence of four major and costly chronic diseases (diabetes,
      cardiovascular disease, cancer, and arthritis) and putative risk factors
      including depressive symptoms within an understudied rural region of the United
      States. These four chronic conditions remain among the most common and
      preventable of health problems across the United States. METHODS: Using survey
      data (N = 2526), logistic regression models were used to assess the association
      of the outcome and risk factors adjusting for age, gender, and race. RESULTS: Key
      findings are (1) Lower financial security was associated with higher prevalence
      of cardiovascular disease, arthritis, and diabetes, but not cancer. (2) Higher
      levels of depressive symptoms were associated with higher prevalence of
      cardiovascular disease, arthritis, and diabetes. (3) Former or current smoking
      was associated with higher prevalence of cardiovascular disease and cancer. (4)
      Blacks reported higher prevalence of diabetes than Whites; Black women were more
      likely to report diabetes than all other groups; prevalence of diabetes was
      greater among women with lower education than among women with higher education.
      (5) Overall, the prevalence of diabetes and arthritis was higher than that
      reported by Florida and national data. CONCLUSIONS: The findings presented in
      this paper are derived from one of only a few studies examining patterns of
      chronic disease among residents of both a rural and lower income geographic
      region. Overall, the prevalence of these conditions compared to the state and
      nation as a whole is elevated and calls for increased attention and tailored
      public health interventions.

PMID- 24083334
TI  - Hyper secretion of Thermobifida fusca beta-glucosidase via a Tat-dependent signal
      peptide using Streptomyces lividans.
AB  - BACKGROUND: Protein production as secretory-form is a powerful tool in industrial
      enzyme production due to the simple purification procedure. Streptomyces lividans
      is a versatile host for secretory production of useful proteins. In order to
      expand the amount of secreted protein, signal peptide sequences, which encourage
      protein secretion from inside cell to extracellular environment, are one of the
      most significant factors. In this study, we focused on Streptomyces lividans as a
      host strain to secrete useful proteins, and screened for signal peptides from the
      biomass-degradation enzymes derived from Thermobifida fusca YX and S. lividans.
      RESULTS: Three candidate signal peptides were isolated and evaluated for their
      protein secretion ability using beta-glucosidase derived from T. fusca YX, which
      is a non-secreted protein, as a model protein. Using S. lividans xylanase C
      signal peptide, the amount of produced the beta-glucosidase reached 10 times as
      much as that when using Streptomyces cinnamoneus phospholipase D signal peptide,
      which was identified as a versatile signal peptide in our previous report. In
      addition, the introduction of the beta-glucosidase fused to xylanase C signal
      peptide using two kinds of plasmid, pUC702 and pTYM18, led to further protein
      secretion, and the maximal level of produced the beta-glucosidase increased up to
      17 times (1.1 g/l) compared to using only pUC702 carrying the beta-glucosidase
      fused to S. cinnamoneus phospholipase D signal peptide. CONCLUSION: In the
      present study, we focused on signal peptide sequences derived from biomass
      degradation enzymes, which are usually secreted into the culture supernatant, and
      screened for signal peptides leading to effective protein secretion. Using the
      signal peptides, the hyper-protein secretion system was successfully demonstrated
      for the cytoplasmic beta-glucosidase.

PMID- 24083335
TI  - Opinions differ by expertise in Mycobacterium avium complex disease.
AB  - RATIONALE: Pulmonary Mycobacterium avium complex treatment guidelines rely
      largely on expert opinion. The extent to which nonexperts agree with
      recommendations of experts in this clinical area is unknown. OBJECTIVES: We
      sought to compare practices and perceptions of prognosis between experts and
      nonexperts. METHODS: We surveyed respirologists (Ontario, Canada, "nonexperts")
      and experts from nontuberculous mycobacterial disease centers of excellence
      (Canada and United States). MEASUREMENTS AND MAIN RESULTS: Forty-six Ontario
      respirologists (29% of 160) and 19 experts (73% of 26) participated. There was
      agreement between nonexperts and experts regarding disease duration before
      diagnosis (2 yr), likelihood of spontaneous remission (7-15%), typical duration
      of treatment (18 mo), first choice of therapy (guideline regimens), a subgroup of
      patients for whom less-intensive regimens are favored (10% after recurrence),
      likelihood of recurrence (30%), and median survival (10 yr in most patients).
      Noted differences were that nonexperts estimated fewer patients with a positive
      culture had disease (30% vs. 50%, P = 0.02), used intensive guidelines therapy
      less often in new cases (50% vs. 79%, P = 0.02), and perceived a slightly lower
      success rate with guidelines therapy (65% vs. 75%, P = 0.047). Response ranges
      were wider for nonexperts, significantly so for selection of intensive guidelines
      therapy in new (P = 0.01) and recurrent (P = 0.04) cases. CONCLUSION: Experts and
      nonexperts agreed on many issues. However, nonexperts perceived lower rates of
      disease among patients with isolates, tended to use less aggressive treatment
      approaches, and perceived lower success rates. Significant variability was
      observed in responses-often wider among nonexperts. Although these results are
      likely biased by referral, they may identify important areas for targeted
      education.

PMID- 24083336
TI  - New antiferromagnetic perovskite CaCo3V4O12 prepared at high-pressure and high
      temperature conditions.
AB  - A new perovskite, CaCo(2+)3V(4+)4O12, has been synthesized at high-pressure and
      high-temperature (HP-HT) conditions. The properties of this perovskite were
      examined by a range of techniques. CaCo3V4O12 was found to adopt a double
      perovskite cubic lattice [a = 7.3428(6) A] with Im3 symmetry. We have established
      that this new perovskite is stable at ambient conditions, and its oxidation
      and/or decomposition at ambient pressure begins above 500  degrees C. It
      undergoes an abrupt antiferromagnetic transition around 98 K. Electrical
      resistivity data suggest semimetallic conductivity in the temperature range of
      1.6-370 K. We have established that the Co(2+) ions in CaCo3V4O12 are in the high
      spin state with a sizable orbital moment, even though their square-planar oxygen
      coordination could be more suitable for the low-spin state, which is prone to
      Jahn-Teller distortion. Electrical resistivity curves also exhibit a distinct
      steplike feature around 100 K. CaCo3V4O12 is a first example of perovskite in
      which the sites A' are fully occupied by Co(2+) ions, and hence its synthesis
      opens the door to a new class of double perovskites, ACo3B4O12, that may be
      derived by chemical substitution of the A sublattice by lanthanides, sodium,
      strontium, and bismuth and by other elements and/or of the B sublattice by some
      other transition metals.

PMID- 24083337
TI  - Naturally-occurring, dually-functional fusions between restriction endonucleases
      and regulatory proteins.
AB  - BACKGROUND: Restriction-modification (RM) systems appear to play key roles in
      modulating gene flow among bacteria and archaea. Because the restriction
      endonuclease (REase) is potentially lethal to unmethylated new host cells,
      regulation to ensure pre-expression of the protective DNA methyltransferase
      (MTase) is essential to the spread of RM genes. This is particularly true for
      Type IIP RM systems, in which the REase and MTase are separate, independently
      active proteins. A substantial subset of Type IIP RM systems are controlled by an
      activator-repressor called C protein. In these systems, C controls the promoter
      for its own gene, and for the downstream REase gene that lacks its own promoter.
      Thus MTase is expressed immediately after the RM genes enter a new cell, while
      expression of REase is delayed until sufficient C protein accumulates. To study
      the variation in and evolution of this regulatory mechanism, we searched for RM
      systems closely related to the well-studied C protein-dependent PvuII RM system.
      Unexpectedly, among those found were several in which the C protein and REase
      genes were fused. RESULTS: The gene for CR.NsoJS138I fusion protein (nsoJS138ICR,
      from the bacterium Niabella soli) was cloned, and the fusion protein produced and
      partially purified. Western blots provided no evidence that, under the conditions
      tested, anything other than full-length fusion protein is produced. This protein
      had REase activity in vitro and, as expected from the sequence similarity, its
      specificity was indistinguishable from that for PvuII REase, though the optimal
      reaction conditions were different. Furthermore, the fusion was active as a C
      protein, as revealed by in vivo activation of a lacZ reporter fusion to the
      promoter region for the nsoJS138ICR gene. CONCLUSIONS: Fusions between C proteins
      and REases have not previously been characterized, though other fusions have
      (such as between REases and MTases). These results reinforce the evidence for
      impressive modularity among RM system proteins, and raise important questions
      about the implications of the C-REase fusions on expression kinetics of these RM
      systems.

PMID- 24083339
TI  - Emergency department waiting room: many requests, many insured and many primary
      care physician referrals.
AB  - BACKGROUND: Increase in waiting time often results in patients leaving the
      emergency department (ED) without being seen, ultimately decreasing patient
      satisfaction. We surveyed low-acuity patients in the ED waiting room to
      understand their preferences and expectations. METHODS: An IRB approved, 42-item
      survey was administered to 400 adult patients waiting in the ED waiting room for
      >15 min from April to August 2010. Demographics, visit reasons, triage and
      waiting room facility preferences were collected. RESULTS: The mean age of
      patients was 38.9 years (SD = 14.8), and 52.5% were females. About 53.8% of
      patients were employed, 79.4% had access to a primary care physician (PCP), and
      17% did not have any medical insurance. The most common complaint was pain. A
      total of 44.4% respondents reported that they believed their problems were urgent
      and required immediate attention, prompting them to come to the ED, while 14.6%
      reported that they could not get a timely PCP appointment, and 42.9% were
      actually referred by their PCP to come to the ED. About 57.7% of patients
      considered leaving the ED if the waiting times were too long. The mean acceptable
      waiting time before leaving ED was 221 min (SD = 194; median 180 min, IQR 120
      270). A total of 39.1% survey respondents reported being most comfortable being
      triaged by a physician. Respondents were least comfortable being triaged by
      residents. On analyzing waiting room expectations for the survey respondents, we
      found that 70% of the subjects wanted a better estimate of waiting time and 43.5%
      wanted better information on reasons for the long wait. CONCLUSION: Contrary to
      popular belief, at our ED a large proportion of low-acuity patients has a PCP and
      is medically insured. Providing patients with appropriate reasons for the wait,
      an accurate estimate of waiting time and creating separate areas to examine minor
      illness/injuries would increase patient satisfaction within our population
      subset.

PMID- 24083340
TI  - Magnetic resonance of the NiFe2O4 nanoparticles in the gigahertz range.
AB  - We report an adjustable magnetic resonance frequency from 1.45 to 2.54 GHz for
      NiFe2O4 nanoparticles which were prepared by a sol-gel process. X-ray diffraction
      and scanning electron microscopy results indicate that the samples are
      polycrystalline nanoparticles, and the size of the particles increases obviously
      with the thermal treatment temperature. The consequence of the surface
      composition suggests that the oxygen defects are present in the nanoparticle
      surface, and this surface magnetic state can show a strong surface anisotropy.
      With decreasing size of the particle, the surface magnetic effect is predominant,
      resulting in an increase of resonance frequency for NiFe2O4 nanoparticles. This
      finding provides a new route for NiFe2O4 materials that can be used in the
      gigahertz range. 

PMID- 24083341
TI  - Should hydroxyethyl starch solutions be totally banned?
AB  - The choice of which intravenous solution to prescribe remains a matter of
      considerable debate in intensive care units around the world. Trends have been
      moving away from using hydroxyethyl starch solutions following concerns about
      safety. But are the available data sufficient to clearly assess the risk-benefit
      balance for all patients, and is there enough evidence of harm to justify
      removing these drugs completely from our hospitals? 

PMID- 24083342
TI  - Online follow-up of individuals with gastroesophageal reflux disease using a
      patient-reported outcomes instrument: results of an observational study.
AB  - BACKGROUND: Many individuals with gastroesophageal reflux disease (GERD) never
      visit their general practitioner. Therefore, prospective data about GERD and its
      natural history in the general population are scarce. The aims of this study were
      to assess symptoms over time and consultation reasons in an Internet population
      with GERD. METHODS: Visitors (18-79 years) to a GERD information website who
      completed the GerdQ self-assessment questionnaire were invited to participate.
      Follow-up GerdQ questionnaires were sent after 4, 12 and 24 weeks, and those who
      had a total GerdQ score >= 8 and responded to at least the baseline and 4-week
      questionnaires (within 2-7 weeks) were included in the analyses. Outcome in
      proton pump inhibitor (PPI) and non-PPI users was classified as symptom
      improvement, symptom persistence/stable symptoms, or symptom relapse according to
      GerdQ scores. RESULTS: A total of 403 non-PPI users (mean age 48 years, 40% male)
      and 304 PPI users (mean age 51 years, 41% male) were included. After 24 weeks,
      symptom improvement was present in 66% of non-PPI users (45/68) and 8% of PPI
      users (6/73), while persisting symptoms were reported by 24% (16/68) and 89%
      (65/73) respectively (baseline symptoms did not influence outcome at 24 weeks).
      Fifty-five percent of PPI users (116/210) and 37% of non-PPI users (76/207) who
      intended to visit a healthcare practitioner, performed one or more healthcare
      visits in the interim. Most frequently reported reason for consultation was
      persistence of symptoms. CONCLUSIONS: GERD symptoms were persistent in the
      majority of PPI users during our 24-week follow-up, while almost two thirds of
      non-PPI users reported symptom improvement. Online follow-up of an Internet
      population with GERD is feasible.

PMID- 24083343
TI  - Social network diagnostics: a tool for monitoring group interventions.
AB  - BACKGROUND: Many behavioral interventions designed to improve health outcomes are
      delivered in group settings. To date, however, group interventions have not been
      evaluated to determine if the groups generate interaction among members and how
      changes in group interaction may affect program outcomes at the individual or
      group level. METHODS: This article presents a model and practical tool for
      monitoring how social ties and social structure are changing within the group
      during program implementation. The approach is based on social network analysis
      and has two phases: collecting network measurements at strategic intervention
      points to determine if group dynamics are evolving in ways anticipated by the
      intervention, and providing the results back to the group leader to guide
      implementation next steps. This process aims to initially increase network
      connectivity and ultimately accelerate the diffusion of desirable behaviors
      through the new network. This article presents the Social Network Diagnostic Tool
      and, as proof of concept, pilot data collected during the formative phase of a
      childhood obesity intervention. RESULTS: The number of reported advice partners
      and discussion partners increased during program implementation. Density, the
      number of ties among people in the network expressed as a percentage of all
      possible ties, increased from 0.082 to 0.182 (p < 0.05) in the advice network,
      and from 0.027 to 0.055 (p > 0.05) in the discussion network. CONCLUSIONS: The
      observed two-fold increase in network density represents a significant shift in
      advice partners over the intervention period. Using the Social Network Tool to
      empirically guide program activities of an obesity intervention was feasible.

PMID- 24083345
TI  - The fabrication of large-scale sub-10-nm core-shell silicon nanowire arrays.
AB  - A combination of template-assisted metal catalytic etching and self-limiting
      oxidation has been successfully implemented to yield core-shell silicon nanowire
      arrays with inner diameter down to sub-10 nm. The diameter of the polystyrene
      spheres after reactive ion etching and the thickness of the deposited Ag film are
      both crucial for the removal of the polystyrene spheres. The mean diameter of the
      reactive ion-etched spheres, the holes on the Ag film, and the nanowires after
      metal catalytic etching exhibit an increasing trend during the synthesis process.
      Two-step dry oxidation and post-chemical etching were employed to reduce the
      diameter of the silicon nanowires to approximately 50 nm. A self-limiting effect
      was induced by further oxidation at lower temperatures (750 degrees C ~ 850
      degrees C), and core-shell silicon nanowire arrays with controllable diameter
      were obtained. 

PMID- 24083344
TI  - 'Girls need to strengthen each other as a group': experiences from a gender
      sensitive stress management intervention by youth-friendly Swedish health
      services--a qualitative study.
AB  - BACKGROUND: Mental health problems among young people, and girls and young women
      in particular, are a well-known health problem. Such gendered mental health
      patterns are also seen in conjunction with stress-related problems, such as
      anxiety and depression and psychosomatic complaints. Thus, intervention models
      tailored to the health care situation experienced by young women within a
      gendered and sociocultural context are needed. This qualitative study aims to
      illuminate young women's experiences of participating in a body-based, gender
      sensitive stress management group intervention by youth-friendly health services
      in northern Sweden. METHODS: A physiotherapeutic body-based, health-promoting,
      gender-sensitive stress management intervention was created by youth-friendly
      Swedish health services. The stress management courses (n = 7) consisted of eight
      sessions, each lasting about two hours, and were led by the physiotherapist at
      the youth centre. The content in the intervention had a gender-sensitive
      approach, combining reflective discussions; short general lectures on, for
      example, stress and pressures related to body ideals; and physiotherapeutic
      methods, including body awareness and relaxation. Follow-up interviews were
      carried out with 32 young women (17-25 years of age) after they had completed the
      intervention. The data were analysed with qualitative content analysis. RESULTS:
      The overall results of our interview analysis suggest that the stress management
      course we evaluated facilitated 'a space for gendered and embodied empowerment in
      a hectic life', implying that it both contributed to a sense of individual growth
      and allowed participants to unburden themselves of stress problems within a
      trustful and supportive context. Participants' narrated experiences of 'finding a
      social oasis to challenge gendered expectations', 'being bodily empowered', and
      'altering gendered positions and stance to life' point to empowering processes of
      change that allowed them to cope with distress, despite sometimes continuously
      stressful life situations. This intervention also decreased stress-related
      symptoms such as anxiousness, restlessness, muscle tension, aches and pains,
      fatigue, and impaired sleep. CONCLUSIONS: The participants' experiences of the
      intervention as a safe and exploratory space for gendered collective
      understanding and embodied empowerment further indicates the need to develop
      gender-sensitive interventions to reduce individualisation of health problems and
      instead encourage spaces for collective support, action, and change.

PMID- 24083346
TI  - Identification of factors for improved ethylene production via the ethylene
      forming enzyme in chemostat cultures of Saccharomyces cerevisiae.
AB  - BACKGROUND: Biotechnological production of the traditional petrochemical ethylene
      is presently being explored using yeasts as well as bacteria. In this study we
      quantify the specific ethylene production levels at different conditions in
      continuous (chemostat) cultivation of Saccharomyces cerevisae expressing the
      ethylene forming enzyme (EFE) from Pseudomonas syringae. RESULTS: Our study shows
      that oxygen availability is an important factor for the ethylene formation.
      Maintaining a high percentage dissolved oxygen in the cultivation was found to be
      necessary to achieve maximal ethylene productivity. Even at oxygen levels high
      enough to sustain respiratory metabolism the ethylene formation was restricted.
      Oxygen was also important for sustaining a high respiratory rate and to re
      oxidize the surplus of NADH that accompanies ethylene formation. By employing
      three different nitrogen sources we further found that the nitrogen source
      available can both improve and impair the ethylene productivity. Contrary to
      findings in batch cultures, using glutamate did not give a significant increase
      in specific ethylene production levels compared to the reference condition with
      ammonia, whereas a combination of glutamate and arginine resulted in a strongly
      diminished specific ethylene production. Furthermore, from cultivations at
      different dilution rates the ethylene formation was found to be coupled to growth
      rate. CONCLUSION: To optimize the ethylene productivity in S. cerevisiae
      expressing a bacterial ethylene forming enzyme, controlling the oxygen
      availability and growth rate as well as employing an ideal nitrogen source is of
      importance. The effects of these factors as studied here provide a basis for an
      optimized process for ethylene production in S. cerevisiae.

PMID- 24083347
TI  - Neurexins.
AB  - The neurexin family of cell adhesion proteins consists of three members in
      vertebrates and has homologs in several invertebrate species. In mammals, each
      neurexin gene encodes an alpha-neurexin in which the extracellular portion is
      long, and a beta-neurexin in which the extracellular portion is short. As a
      result of alternative splicing, both major isoforms can be transcribed in many
      variants, contributing to distinct structural domains and variability. Neurexins
      act predominantly at the presynaptic terminal in neurons and play essential roles
      in neurotransmission and differentiation of synapses. Some of these functions
      require the formation of trans-synaptic complexes with postsynaptic proteins such
      as neuroligins, LRRTM proteins or cerebellin. In addition, rare mutations and
      copy-number variations of human neurexin genes have been linked to autism and
      schizophrenia, indicating that impairments of synaptic function sustained by
      neurexins and their binding partners maybe relevant to the pathomechanism of
      these debilitating diseases.

PMID- 24083348
TI  - Stacking resistance to crown gall and nematodes in walnut rootstocks.
AB  - BACKGROUND: Crown gall (CG) (Agrobacterium tumefaciens) and the root lesion
      nematodes (RLNs) (Pratylenchus vulnus) are major challenges faced by the
      California walnut industry, reducing productivity and increasing the cost of
      establishing and maintaining orchards. Current nematode control strategies
      include nematicides, crop rotation, and tolerant cultivars, but these methods
      have limits. Developing genetic resistance through novel approaches like RNA
      interference (RNAi) can address these problems. RNAi-mediated silencing of CG
      disease in walnut (Juglans regia L.) has been achieved previously. We sought to
      place both CG and nematode resistance into a single walnut rootstock genotype
      using co-transformation to stack the resistance genes. A. tumefaciens, carrying
      self-complimentary iaaM and ipt transgenes, and Agrobacterium rhizogenes,
      carrying a self-complimentary Pv010 gene from P. vulnus, were used as co
      transformation vectors. RolABC genes were introduced by the resident T-DNA in the
      A. rhizogenes Ri-plasmid used as a vector for plant transformation. Pv010 and
      Pv194 (transgenic control) genes were also transferred separately using A.
      tumefaciens. To test for resistance, transformed walnut roots were challenged
      with P. vulnus and microshoots were challenged with a virulent strain of A.
      tumefaciens. RESULTS: Combining the two bacterial strains at a 1:1 rather than
      1:3 ratio increased the co-transformation efficiency. Although complete immunity
      to nematode infection was not observed, transgenic lines yielded up to 79% fewer
      nematodes per root following in vitro co-culture than untransformed controls.
      Transgenic line 33-3-1 exhibited complete crown gall control and 32% fewer
      nematodes. The transgenic plants had thicker, longer roots than untransformed
      controls possibly due to insertion of rolABC genes. When the Pv010 gene was
      present in roots with or without rolABC genes there was partial or complete
      control of RLNs. Transformation using only one vector showed 100% control in some
      lines. CONCLUSIONS: CG and nematode resistance gene stacking controlled CG and
      RLNs simultaneously in walnuts. Silencing genes encoding iaaM, ipt, and Pv010
      decrease CG formation and RLNs populations in walnut. Beneficial plant genotype
      and phenotype changes are caused by co-transformation using A. tumefaciens and A.
      rhizogenes strains. Viable resistance against root lesion nematodes in walnut
      plants may be accomplished in the future using this gene stacking technology.

PMID- 24083349
TI  - Whole-exome sequencing supports genetic heterogeneity in childhood apraxia of
      speech.
AB  - BACKGROUND: Childhood apraxia of speech (CAS) is a rare, severe, persistent
      pediatric motor speech disorder with associated deficits in sensorimotor,
      cognitive, language, learning and affective processes. Among other neurogenetic
      origins, CAS is the disorder segregating with a mutation in FOXP2 in a widely
      studied, multigenerational London family. We report the first whole-exome
      sequencing (WES) findings from a cohort of 10 unrelated participants, ages 3 to
      19 years, with well-characterized CAS. METHODS: As part of a larger study of
      children and youth with motor speech sound disorders, 32 participants were
      classified as positive for CAS on the basis of a behavioral classification marker
      using auditory-perceptual and acoustic methods that quantify the competence,
      precision and stability of a speaker's speech, prosody and voice. WES of 10
      randomly selected participants was completed using the Illumina Genome Analyzer
      IIx Sequencing System. Image analysis, base calling, demultiplexing, read
      mapping, and variant calling were performed using Illumina software. Software
      developed in-house was used for variant annotation, prioritization and
      interpretation to identify those variants likely to be deleterious to
      neurodevelopmental substrates of speech-language development. RESULTS: Among
      potentially deleterious variants, clinically reportable findings of interest
      occurred on a total of five chromosomes (Chr3, Chr6, Chr7, Chr9 and Chr17), which
      included six genes either strongly associated with CAS (FOXP1 and CNTNAP2) or
      associated with disorders with phenotypes overlapping CAS (ATP13A4, CNTNAP1,
      KIAA0319 and SETX). A total of 8 (80%) of the 10 participants had clinically
      reportable variants in one or two of the six genes, with variants in ATP13A4,
      KIAA0319 and CNTNAP2 being the most prevalent. CONCLUSIONS: Similar to the
      results reported in emerging WES studies of other complex neurodevelopmental
      disorders, our findings from this first WES study of CAS are interpreted as
      support for heterogeneous genetic origins of this pediatric motor speech disorder
      with multiple genes, pathways and complex interactions. We also submit that our
      findings illustrate the potential use of WES for both gene identification and
      case-by-case clinical diagnostics in pediatric motor speech disorders.

PMID- 24083351
TI  - Using neoadjuvant chemotherapy and replanning intensity-modulated radiotherapy
      for nasopharyngeal carcinoma with intracranial invasion to protect critical
      normal tissue.
AB  - PURPOSE: To investigate the feasibility of neoadjuvant chemotherapy and
      replanning intensity-modulated radiotherapy (IMRT) for intracranial invasion
      nasopharyngeal carcinoma (NPC). METHODS AND MATERIALS: From June 2007 to January
      2012, 32 patients with intracranial invasion NPC treated with TPF (docetaxel 75
      mg/m2, cisplatin 75 mg/m2, 5-FU 2500 mg/m2 every 3 weeks for 3 cycles)
      neoadjuvant chemotherapy, and replanning IMRT with concurrent chemotherapy were
      retrospectively studied. The first IMRT plan for each patient was generated based
      on the original planning CT scan acquired before the start of treatment. Because
      of tumor shrinkage during radiotherapy, modified gross tumor volume of primary
      tumor (GTV-P) and high risk clinical target volume (CTV-H), and a new plan was
      generated and used to complete the course of IMRT. The DVHs of IMRT plan with or
      without replanning were compared. RESULTS: There weren't statistically
      significant differences in the V95, D-mean, D-95, and D-99 to the modified PTVGTV
      P and PTVCTV-H with and without replanning IMRT. Replanning reduced the doses to
      the brain stem, optic nerve, optic chiasm and temporal lobe. Objective responses
      were 100.0% 3 months after completion of radiotherapy. Acute toxicities were well
      tolerated, except for the relatively high incidence of neutropenia. The 2-year
      local control rates and distant-metastasis free survival were 88.2% (95% CI,
      72.9% to 100.0%) and 89.6% (95% CI, 75.9% to 100.0%). CONCLUSION: Neoadjuvant
      chemotherapy and replanning IMRT according to tumor shrinkage during the
      treatment is essential to ensure safe doses to normal tissues, and produces
      encouraging outcome for intracranial invasion NPC.

PMID- 24083350
TI  - Possible etiology of improvements in both quality of life and overlapping
      gastroesophageal reflux disease by proton pump inhibitor treatment in a
      prospective randomized controlled trial.
AB  - BACKGROUND: Symptoms suggestive of functional dyspepsia (FD) and irritable bowel
      syndrome (IBS) frequently overlap with those of gastroesophageal reflux disease.
      Despite the high prevalence of symptomatic overlap, the underlying etiology
      remains poorly defined. We assessed the correlation of symptomatic relief and
      health-related quality of life (HRQoL) with healing of reflux esophagitis to
      further derive insights into the underlying etiology. METHODS: 626 patients with
      reflux esophagitis were enrolled into one of two treatment groups (classical
      healing concept or the complete remission concept) to investigate differences in
      treatment intensity. Patients were treated with pantoprazole until esophageal
      mucosal healing. Remission was followed for up to 6 months without treatment.
      Gastro-intestinal symptoms and HRQoL were analyzed using disease-specific,
      psychometrically validated patient-reported outcome instruments (ReQuestTM,
      GERDyzerTM). RESULTS: Symptomatic burden reflected by ReQuestTM substantially
      decreased from baseline to end of treatment by 83% and 88% in either treatment
      group, respectively. ReQuestTM scores significantly decreased in patients with or
      without heartburn and in those with symptoms suggestive of FD and IBS, indicating
      response of all symptom categories to treatment (p < 0.005). Therapy-associated
      relief of symptoms was paralleled by substantial gains in HRQoL, which continued
      to stabilize post-treatment. CONCLUSIONS: Pantoprazole is effective in relieving
      upper and lower gastro-intestinal symptoms overlapping with erosive esophagitis,
      and provides sustained improvement in HRQoL post-treatment. Our results propose a
      link between both healing of erosive esophagitis and the slower remission of
      upper and lower gastro-intestinal symptoms. Since the improvement observed is
      likely to be multifactorial, the possibility for an immune-mediated etiology and
      identification of putative susceptibility factors by genome-wide association
      study may provide focus for future research. TRIAL REGISTRATION:
      ClinicalTrials.gov identifier: NCT00325676.

PMID- 24083352
TI  - Immunization coverage and predictive factors for complete and age-appropriate
      vaccination among preschoolers in Athens, Greece: a cross--sectional study.
AB  - BACKGROUND: In Greece, several new childhood vaccines were introduced recently
      but were reimbursed gradually and at different time points. The aim of this study
      was to assess immunization coverage and identify factors influencing complete and
      age-appropriate vaccination among children attending public nurseries in the
      municipal district of Athens. METHODS: A cross-sectional study, using stratified
      sampling was performed. Immunization history was obtained from vaccination
      booklets. Demographic and socioeconomic data were obtained from school registries
      and telephone interviews. Vaccination rates were estimated by sample weighted
      proportions while associations between complete and age-appropriate immunization
      and potential determinants by logistic regression analysis. RESULTS: A total of
      731 children (mean age: 46, median: 48, range: 10-65 months) were included.
      Overall immunization coverage with traditional vaccines (DTP, polio, Hib, HBV,
      1st dose MMR) was satisfactory, exceeding 90%, but the administration of booster
      doses was delayed (range: 33.7- 97.4%, at 60 months of age). Complete vaccination
      rates were lower for new vaccines (Men C, PCV7, varicella, hepatitis A), ranging
      between 61-92%. In addition, a significant delay in timely administration of Men
      C, PCV7, as well as HBV was noted (22.9%, 16.0% and 27.7% at 12 months of age,
      respectively). Child's age was strongly associated with incomplete vaccination
      with all vaccines (p< 0.001), while as immigrant status was a predictor of
      incomplete (p=0.034) and delayed vaccination (p<0.001) with traditional vaccines.
      Increasing household size and higher maternal education were negatively
      associated with the receipt of all and newly licensed vaccines, respectively
      (p=0.035). CONCLUSIONS: Our findings highlight the need to monitor uptake of new
      vaccines and improve age- appropriate administration of booster doses as well as
      early vaccination against hepatitis B. Immigrant status, increased household size
      and high maternal education may warrant targeted intervention.

PMID- 24083353
TI  - Agro-ecosystems impact malaria prevalence: large-scale irrigation drives vector
      population in western Ethiopia.
AB  - BACKGROUND: Development strategies in Ethiopia have largely focused on the
      expansion of irrigated agriculture in the last decade to reduce poverty and
      promote economic growth. However, such irrigation schemes can worsen the socio
      economic state by aggravating the problem of mosquito-borne diseases. In this
      study, the effect of agro-ecosystem practices on malaria prevalence and the risk
      of malaria transmission by the primary vector mosquito, Anopheles arabiensis, in
      Ethiopia were investigated. METHODS: In three villages in western Ethiopia
      practising large-scale sugarcane irrigation, traditional smallholder irrigation
      and non-irrigated farming, cross-sectional parasitological surveys were conducted
      during the short rains, after the long rains and during the dry season.
      Entomological surveys were undertaken monthly (February 2010-January 2011) in
      each village using light traps, pyrethrum spray collections and artificial pit
      shelters. RESULTS: Malaria prevalence and the risk of transmission by An.
      arabiensis assessed by the average human biting rate, mean sporozoite rate and
      estimated annual entomological inoculation rate were significantly higher in the
      irrigated sugarcane agro-ecosystem compared to the traditionally irrigated and
      non-irrigated agro-ecosystems. The average human biting rate was significantly
      elevated by two-fold, while the mean sporozoite rate was 2.5-fold higher, and the
      annual entomological inoculation rate was 4.6 to 5.7-fold higher in the irrigated
      sugarcane compared to the traditional and non-irrigated agro-ecosystems. Active
      irrigation clearly affected malaria prevalence by increasing the abundance of
      host seeking Anopheles mosquitoes year-round and thus increasing the risk of
      infective bites. The year-round presence of sporozoite-infected vectors due to
      irrigation practices was found to strengthen the coupling between rainfall and
      risk of malaria transmission, both on- and off-season. CONCLUSION: This study
      demonstrates the negative impact of large-scale irrigation expansion on malaria
      transmission by increasing the abundance of mosquito vectors and indicates the
      need for effective vector monitoring and control strategies in the implementation
      of irrigation projects.

PMID- 24083356
TI  - The relationship between consumption of tyrosine and phenylalanine as precursors
      of catecholamine at breakfast and the circadian typology and mental health in
      Japanese infants aged 2 to 5 years.
AB  - BACKGROUND: This study aims to examine the relationship between tyrosine and
      phenylalanine intake at breakfast as precursors of dopamine, and scores on the
      Torsvall-Akerstedt Diurnal Type Scale and of mental health in Japanese infants
      aged 2 to 5 years. RESULTS: An integrated questionnaire was administered to
      parents of 1,367 infants attending one of ten nursery schools governed by Kochi
      City or a kindergarten affiliated with the Faculty of Education at Kochi
      University (775 answers for analysis: 56.7%) in May and June 2008. Questionnaires
      included the Torsvall-Akerstedt Diurnal Type Scale and questions on sleep habits
      (onset, offset, quality, quantity, and so on), meal habits (content and
      regularity of timing), and mental health (depressive states). Amount of tyrosine
      and phenylalanine intake was calculated based on a breakfast content
      questionnaire and data on the components of amino acids in foods. Infants who
      ingested more than 800 mg of tyrosine or phenylalanine at breakfast per meal were
      more morning-type than those who ingested less than 800 mg (ANOVA: P= 0.005).
      However, this relationship disappeared in the ANCOVA analysis (with the
      covariance of tryptophan intake, P= 0.894). Infants who ingested more than 800 mg
      of the two amino acids at breakfast showed significantly higher mental health
      scores (lower frequency of depressive states) than those who ingested less than
      800 mg (ANOVA: P = 0.004). This relationship remained significant when ANCOVA
      analysis was performed with the covariance of tryptophan (ANCOVA: P= 0.017).
      CONCLUSIONS: These results suggest that tyrosine and phenylalanine ingested at
      breakfast are not related with circadian phase, but are relate with mental health
      in infants.

PMID- 24083357
TI  - Prevalence and spectrum of PITX2c mutations associated with congenital heart
      disease.
AB  - Congenital heart disease (CHD) is the most common form of birth defect and is the
      leading noninfectious cause of infant death. A growing body of evidence
      demonstrates that genetic risk factors are involved in the pathogenesis of CHD.
      However, CHD is a genetically heterogeneous disease and the genetic defects
      underlying CHD in an overwhelming majority of patients remain unclear. In this
      study, the whole coding region and splice junction sites of the PITX2c gene,
      which encodes variant 3 of paired-like homeodomain transcription factor 2 crucial
      for normal cardiovascular morphogenesis, were sequenced in 382 unrelated patients
      with CHD, and 2 novel heterozygous mutations, p.W147X and p.N153D, were
      identified in 2 unrelated patients with CHD, respectively, including a 1-year-old
      male patient with double outlet right ventricle in combination with ventricular
      septal defect and a 4-year-old female patient with ventricular septal defect. The
      mutations were absent in 400 control chromosomes and were both predicted to be
      disease-causing by MutationTaster. Multiple alignments of PITX2c proteins across
      species displayed that the altered amino acids were completely conserved
      evolutionarily. Functional analysis revealed that the mutated PITX2c proteins
      were associated with a significantly reduced transactivational activity compared
      with their wild-type counterpart. These findings provide a novel insight into the
      molecular mechanisms implicated in CHD, suggesting potential implications for the
      antenatal prophylaxis and allele-specific treatment of CHD. 

PMID- 24083358
TI  - Effect of soluble inducible costimulator level and its polymorphisms on age
      related macular degeneration.
AB  - Age-related macular degeneration (AMD) is the leading cause of blindness in the
      elderly population. Evidence has shown that the human immune system may play
      critical roles in this disease. Inducible costimulator (ICOS) promotes T-cell
      activation, differentiation, and T:B-cell interactions. The aim of the study was
      to understand the effect of ICOS on the development of AMD from genetic
      polymorphism perspective and serum level perspective. Two ICOS polymorphisms,
      rs10183087A/C and rs10932037C/T, were tested in 223 AMD cases and 262 healthy
      controls. The serum level of soluble ICOS (sICOS) was compared among subjects
      with different genotypes, as well as between AMD patients and controls. Data
      showed that prevalence of rs10183087CC genotype was significantly increased in
      AMD than in controls (p=0.001). Function analysis revealed that subjects carrying
      rs10183087CC genotype had higher serum levels of sICOS than those with AA or AC
      genotypes (p<0.05). When we compared serum levels of sICOS between cases and
      controls, results showed that AMD patients had significantly increased sICOS
      levels than healthy donors (p<0.05). Also, wet type cases were observed to have
      higher sICOS levels than cases with dry type (p<0.05). These data suggested ICOS
      polymorphism could affect the susceptibility to AMD by elevating protein
      expression, and serum levels of sICOS may be closed correlated with the
      development and progression of this disease. 

PMID- 24083360
TI  - Heteroleptic copper(I) complexes prepared from phenanthroline and bis-phosphine
      ligands.
AB  - Preparation of [Cu(NN)(PP)](+) derivatives has been systematically investigated
      starting from two libraries of phenanthroline (NN) derivatives and bis-phosphine
      (PP) ligands, namely, (A) 1,10-phenanthroline (phen), neocuproine (2,9-dimethyl
      1,10-phenanthroline, dmp), bathophenanthroline (4,7-diphenyl-1,10-phenanthroline,
      Bphen), 2,9-diphenethyl-1,10-phenanthroline (dpep), and 2,9-diphenyl-1,10
      phenanthroline (dpp); (B) bis(diphenylphosphino)methane (dppm), 1,2
      bis(diphenylphosphino)ethane (dppe), 1,3-bis(diphenylphosphino)propane (dppp),
      1,2-bis(diphenylphosphino)benzene (dppb), 1,1'-bis(diphenylphosphino)ferrocene
      (dppFc), and bis[(2-diphenylphosphino)phenyl] ether (POP). Whatever the bis
      phosphine ligand, stable heteroleptic [Cu(NN)(PP)](+) complexes are obtained from
      the 2,9-unsubstituted-1,10-phenanthroline ligands (phen and Bphen). By contrast,
      heteroleptic complexes obtained from dmp and dpep are stable in the solid state,
      but a dynamic ligand exchange reaction is systematically observed in solution,
      and the homoleptic/heteroleptic ratio is highly dependent on the bis-phosphine
      ligand. Detailed analysis revealed that the dynamic equilibrium resulting from
      ligand exchange reactions is mainly influenced by the relative thermodynamic
      stability of the different possible complexes. Finally, in the case of dpp, only
      homoleptic complexes were obtained whatever the bis-phosphine ligand. Obviously,
      steric effects resulting from the presence of the bulky phenyl rings on the dpp
      ligand destabilize the heteroleptic [Cu(NN)(PP)](+) complexes. In addition to the
      remarkable thermodynamic stability of [Cu(dpp)2]BF4, this negative steric effect
      drives the dynamic complexation scenario toward almost exclusive formation of
      homoleptic [Cu(NN)2](+) and [Cu(PP)2](+) complexes. This work provides the
      definitive rationalization of the stability of [Cu(NN)(PP)](+) complexes, marking
      the way for future developments in this field. 

PMID- 24083359
TI  - The transmembrane domains of the bacterial cell division proteins FtsB and FtsL
      form a stable high-order oligomer.
AB  - FtsB and FtsL are two essential integral membrane proteins of the bacterial
      division complex or "divisome", both characterized by a single transmembrane
      helix and a juxtamembrane coiled coil domain. The two domains are important for
      the association of FtsB and FtsL, a key event for their recruitment to the
      divisome, which in turn allows the recruitment of the late divisomal components
      to the Z-ring and subsequent completion of the division process. Here we present
      a biophysical analysis performed in vitro that shows that the transmembrane
      domains of FtsB and FtsL associate strongly in isolation. Using Forster resonance
      energy transfer, we have measured the oligomerization of fluorophore-labeled
      transmembrane domains of FtsB and FtsL in both detergent and lipid. The data
      indicate that the transmembrane helices are likely a major contributor to the
      stability of the FtsB-FtsL complex. Our analyses show that FtsB and FtsL form a
      1:1 higher-order oligomeric complex, possibly a tetramer. This finding suggests
      that the FtsB-FtsL complex is capable of multivalent binding to FtsQ and other
      divisome components, a hypothesis that is consistent with the possibility that
      the FtsB-FtsL complex has a structural role in the stabilization of the Z-ring. 

PMID- 24083361
TI  - Spacer effect on nanostructures and self-assembly in organogels via some bolaform
      cholesteryl imide derivatives with different spacers.
AB  - In this paper, new bolaform cholesteryl imide derivatives with different spacers
      were designed and synthesized. Their gelation behaviors in 23 solvents were
      investigated, and some of them were found to be low molecular mass organic
      gelators. The experimental results indicated that these as-formed organogels can
      be regulated by changing the flexible/rigid segments in spacers and organic
      solvents. Suitable combination of flexible/rigid segments in molecular spacers in
      the present cholesteryl gelators is favorable for the gelation of organic
      solvents. Scanning electron microscopy and atomic force microscopy observations
      revealed that the gelator molecules self-assemble into different aggregates, from
      wrinkle and belt to fiber with the change of spacers and solvents. Spectral
      studies indicated that there existed different H-bond formations between imide
      groups and assembly modes, depending on the substituent spacers in molecular
      skeletons. The present work may give some insight into the design and character
      of new organogelators and soft materials with special molecular structures. 

PMID- 24083362
TI  - Effective piezoelectric response of substrate-integrated ZnO nanowire array
      devices on galvanized steel.
AB  - Harvesting waste energy through electromechanical coupling in practical devices
      requires combining device design with the development of synthetic strategies for
      large-area controlled fabrication of active piezoelectric materials. Here, we
      show a facile route to the large-area fabrication of ZnO nanostructured arrays
      using commodity galvanized steel as the Zn precursor as well as the substrate.
      The ZnO nanowires are further integrated within a device construct and the
      effective piezoelectric response is deduced based on a novel experimental
      approach involving induction of stress in the nanowires through pressure wave
      propagation along with phase-selective lock-in detection of the induced current.
      The robust methodology for measurement of the effective piezoelectric coefficient
      developed here allows for interrogation of piezoelectric functionality for the
      entire substrate under bending-type deformation of the ZnO nanowires. 

PMID- 24083365
TI  - Prediction and prevention of failure: an early intervention to assist at-risk
      medical students.
AB  - BACKGROUND: Consistent identification and prevention of failure for at-risk
      medical students is challenging, failing courses is costly to all stakeholders,
      and there is need for further research into duration, timing and structure of
      interventions to help students in difficulty. AIMS: To verify the value of a new
      exam two weeks into medical school as a predictor of failure, and explore the
      requirements for a preventative intervention. METHODS: Students who failed the
      two-week exam were invited to a series of large-group workshops and small-group
      follow-up meetings. Participants' subsequent exam performance was compared with
      non-participants. RESULTS: About 71% of students who performed poorly in the new
      exam subsequently failed a course. Attendance at the workshops made no difference
      to short- or long-term pass rates. Attendance at more than three follow-up small
      group sessions significantly improved pass rates two semesters later, and was
      influenced by teacher experience. CONCLUSIONS: Close similarity between predictor
      task and target task is important for accurate prediction of failure.
      Consideration should be given to dose effect and class size in the prevention of
      failure of at-risk students, and we recommend a systemic approach to
      intervention/remediation programmes, involving a whole semester of mandatory,
      weekly small group meetings with experienced teachers.

PMID- 24083366
TI  - Fabricating superhydrophobic surfaces via a two-step electrodeposition technique.
AB  - This work presents a template-free electrochemical route to producing
      superhydrophobic copper coatings with the water contact angle of 160 +/- 6
      degrees  and contact angle hysteresis of 5 +/- 2 degrees . In this technique,
      copper deposit with multiscale surface features is formed through a two-step
      electrodeposition process in a concentrated copper sulfate bath. In the first
      step, applying a high overpotential results in the formation of structures with
      dense-branching morphology, which are loosely attached to the surface. In the
      second step, an additional thin layer of the deposit is formed by applying a low
      overpotential for a short time, which is used to reinforce the loosely attached
      branches on the surface. The work also presents a theoretical analysis of the
      effects of the fabrication parameters on the surface textures that cause the
      superhydrophobic characteristic of the deposit. 

PMID- 24083367
TI  - A randomized controlled trial comparing health and quality of life of lung
      transplant recipients following nurse and computer-based triage utilizing home
      spirometry monitoring.
AB  - BACKGROUND: Lung transplantation is now a standard intervention for patients with
      advanced lung disease. Home monitoring of pulmonary function and symptoms has
      been used to follow the progress of lung transplant recipients in an effort to
      improve care and clinical status. The study objective was to determine the
      relative performance of a computer-based Bayesian algorithm compared with a
      manual nurse decision process for triaging clinical intervention in lung
      transplant recipients participating in a home monitoring program. MATERIALS AND
      METHODS: This randomized controlled trial had 65 lung transplant recipients
      assigned to either the Bayesian or nurse triage study arm. Subjects monitored and
      transmitted spirometry and respiratory symptoms daily to the data center using an
      electronic spirometer/diary device. Subjects completed the Short Form-36 (SF-36)
      survey at baseline and after 1 year. End points were change from baseline after 1
      year in forced expiratory volume at 1 s (FEV1) and quality of life (SF-36 scales)
      within and between each study arm. RESULTS: There were no statistically
      significant differences between groups in FEV1 or SF-36 scales at baseline or
      after 1 year.: Results were comparable between nurse and Bayesian system for
      detecting changes in spirometry and symptoms, providing support for using
      computer-based triage support systems as remote monitoring triage programs become
      more widely available. CONCLUSIONS: The feasibility of monitoring critical
      patient data with a computer-based decision system is especially important given
      the likely economic constraints on the growth in the nurse workforce capable of
      providing these early detection triage services.

PMID- 24083368
TI  - A web search on environmental topics: what is the role of ranking?
AB  - BACKGROUND: Although the Internet is easy to use, the mechanisms and logic behind
      a Web search are often unknown. Reliable information can be obtained, but it may
      not be visible as the Web site is not located in the first positions of search
      results. The possible risks of adverse health effects arising from environmental
      hazards are issues of increasing public interest, and therefore the information
      about these risks, particularly on topics for which there is no scientific
      evidence, is very crucial. The aim of this study was to investigate whether the
      presentation of information on some environmental health topics differed among
      various search engines, assuming that the most reliable information should come
      from institutional Web sites. MATERIALS AND METHODS: Five search engines were
      used: Google, Yahoo!, Bing, Ask, and AOL. The following topics were searched in
      combination with the word "health": "nuclear energy," "electromagnetic waves,"
      "air pollution," "waste," and "radon." For each topic three key words were used.
      The first 30 search results for each query were considered. The ranking
      variability among the search engines and the type of search results were analyzed
      for each topic and for each key word. The ranking of institutional Web sites was
      given particular consideration. RESULTS: Variable results were obtained when
      surfing the Internet on different environmental health topics. Multivariate
      logistic regression analysis showed that, when searching for radon and air
      pollution topics, it is more likely to find institutional Web sites in the first
      10 positions compared with nuclear power (odds ratio=3.4, 95% confidence interval
      2.1-5.4 and odds ratio=2.9, 95% confidence interval 1.8-4.7, respectively) and
      also when using Google compared with Bing (odds ratio=3.1, 95% confidence
      interval 1.9-5.1). CONCLUSIONS: The increasing use of online information could
      play an important role in forming opinions. Web users should become more aware of
      the importance of finding reliable information, and health institutions should be
      able to make that information more visible.

PMID- 24083369
TI  - Laparoscopic liver resection as a safe and efficacious alternative to open
      resection for colorectal liver metastasis: a meta-analysis.
AB  - BACKGROUND: The safety and efficacy of laparoscopic liver resection (LLR) for
      colorectal liver metastasis (CLM) remain to be established. A meta-analysis was
      undertaken to compare LLR and open liver resection (OLR) for CLM with respect to
      surgical and oncologic outcomes. METHODS: An electronic search was performed to
      retrieve all relevant articles published in the English language by the end of
      March 2013. Data were analyzed using Review Manager version 5.0. RESULTS: A total
      of 8 nonrandomized controlled studies with 695 subjects were analyzsed. Intra
      operative blood loss, the proportion of patients requiring blood transfusion,
      morbidity and the length of hospital stay were all significantly reduced after
      LLR. Postoperative recurrence, 5-year overall and disease-free survivals were
      comparable between two groups. CONCLUSIONS: LLR for CLM is safe and efficacious.
      It improves surgical outcomes and uncompromises oncologic outcomes as compared
      with OLR.

PMID- 24083370
TI  - Gut microbiota dysbiosis and bacterial community assembly associated with
      cholesterol gallstones in large-scale study.
AB  - BACKGROUND: Elucidating gut microbiota among gallstone patients as well as the
      complex bacterial colonization of cholesterol gallstones may help in both the
      prediction and subsequent lowered risk of cholelithiasis. To this end, we studied
      the composition of bacterial communities of gut, bile, and gallstones from 29
      gallstone patients as well as the gut of 38 normal individuals, examining and
      analyzing some 299, 217 bacterial 16S rRNA gene sequences from 120 samples.
      RESULTS: First, as compared with normal individuals, in gallstone patients there
      were significant (P < 0.001) increases of gut bacterial phylum Proteobacteria and
      decreases of three gut bacterial genera, Faecalibacterium, Lachnospira, and
      Roseburia. Second, about 70% of gut bacterial operational taxonomic units (OTUs)
      from gallstone patients were detectable in the biliary tract and bacteria
      diversity of biliary tract was significantly (P < 0.001) higher than that of gut.
      Third, analysis of the biliary tract core microbiome (represented by 106 bacteria
      OTUs) among gallstone patients showed that 33.96% (36/106) of constituents can be
      matched to known bacterial species (15 of which have publicly available genomes).
      A genome-wide search of MDR, BSH, bG, and phL genes purpotedly associated with
      the formation of cholesterol gallstones showed that all 15 species with known
      genomes (e.g., Propionibacterium acnes, Bacteroides vulgates, and Pseudomonas
      putida) contained at least contained one of the four genes. This finding could
      potentially provide underlying information needed to explain the association
      between biliary tract microbiota and the formation of cholesterol gallstones.
      CONCLUSIONS: To the best of our knowledge, this is the first study to discover
      gut microbiota dysbiosis among gallstone patients, the presence of which may be a
      key contributor to the complex bacteria community assembly linked with the
      presence of cholesterol gallstones. Likewise, this study also provides the first
      large-scale glimpse of biliary tract microbiota potentially associated with
      cholesterol gallstones. Such a characterization of the biliary tract core
      microbiome has potentially important biological and medical implications
      regarding the role of bacteria in the formation cholesterol gallstones.

PMID- 24083374
TI  - Relative contribution of combined kinetic and exchange energy terms vs the
      electronic component of molecular electrostatic potential in hardness potential
      derivatives.
AB  - The relative contribution of the sum of kinetic [(10/9)CFrho(r)2/3] and exchange
      energy [(4/9)CXrho(r)1/3] terms to that of the electronic part of the molecular
      electrostatic potential [Vel(r)] in the variants of hardness potential is
      investigated to assess the proposed definition of Delta+h(k) = -[VelN+1(k) -
      VelN(k)] and Delta-h(k) = -[VelN(k) - VelN-1(k)] (Saha; et al. J. Comput. Chem.
      2013, 34, 662). Some substituted benzenes and polycyclic aromatic hydrocarbons
      (PAHs) (undergoing electrophilic aromatic substitution), carboxylic acids, and
      their derivatives are chosen to carry out the theoretical investigation as stated
      above. Intra- and intermolecular reactivity trends generated by Delta+h(k) and
      Delta-h(k) are found to be satisfactory and are correlated reasonably well with
      experimental results.

PMID- 24083371
TI  - A synthetic peptide-acrylate surface for production of insulin-producing cells
      from human embryonic stem cells.
AB  - Human embryonic stem cells (hESCs), due to their self-renewal capacity and
      pluripotency, have become a potential source of transplantable beta-cells for the
      treatment of diabetes. However, it is imperative that the derived cells fulfill
      the criteria for clinical treatment. In this study, we replaced common Matrigel
      with a synthetic peptide-acrylate surface (Synthemax) to expand undifferentiated
      hESCs and direct their differentiation in a defined and serum-free medium. We
      confirmed that the cells still expressed pluripotent markers, had the ability to
      differentiate into three germ layers, and maintained a normal karyotype after 10
      passages of subculture. Next, we reported an efficient protocol for deriving
      nearly 86% definitive endoderm cells from hESCs under serum-free conditions.
      Moreover, we were able to obtain insulin-producing cells within 21 days following
      a simple three-step protocol. The results of immunocytochemical and quantitative
      gene expression analysis showed that the efficiency of induction was not
      significantly different between the Synthemax surface and the Matrigel-coated
      surface. Thus, we provided a totally defined condition from hESC culture to
      insulin-producing cell differentiation, and the derived cells could be a
      therapeutic resource for diabetic patients in the future.

PMID- 24083375
TI  - Retrospective analysis of antimicrobial resistance and bacterial spectrum of
      infection in Gabon, Central Africa.
AB  - BACKGROUND: Physicians depend on reliable information on the local epidemiology
      of infection and antibiotic resistance rates to guide empiric treatment in
      critically ill patients. As these data are scarce for Central Africa, we
      performed a retrospective analysis of microbiological findings from a secondary
      care hospital in Gabon. METHODS: Microbiological reports from 2009 to 2012 were
      used to assess the non-susceptibility rates of the three most common isolates
      from six major types of infections (bloodstream, ear-eye-nose-throat, surgical
      site, skin and soft tissue, urinary tract and wound infection). RESULTS: A high
      diversity of pathogens was found, but Staphylococcus aureus was predominant in
      the majority of infections. Overall, the three most prevalent pathogens in
      children were S. aureus (33.7%), Streptococcus pyogenes (8.1%) and Escherichia
      coli (4.5%) and in adults S. aureus (23.5%), E. coli (15.1%) and Klebsiella
      pneumoniae (7.4%). In total, 5.8% (n = 19) of all S. aureus isolates were
      methicillin resistant. The proportion of extended-spectrum beta-lactamase (ESBL)
      producing Enterobacteriaceae was 15.4% (n = 78), 49.4% of all K. pneumoniae were
      ESBL-producer (n = 42). CONCLUSION: The high diversity of potential pathogens and
      high resistance rates in Gram-negative bacteria challenge a rational empiric use
      of antibiotics. Countrywide continuous sentinel surveillance is therefore
      urgently needed.

PMID- 24083376
TI  - Red-light-driven photocatalytic reduction of CO2 using Os(II)-Re(I)
      supramolecular complexes.
AB  - The novel supramolecular complexes, which are composed of an [Os(5dmb)2(BL)](2+)
      type complex (5dmb = 5,5'-dimethyl-2,2'-bipyridine; BL = 1,2-bis(4'-methyl-[2,2'
      bipyridin]-4-yl)ethane) as a photosensitizer and cis,trans-[Re(BL)(CO)2{P(p-X
      C6H4)3}2](+)-type complexes (X = F, Cl) as a catalyst, have been synthesized.
      They photocatalyzed selective reduction of CO2 to CO under red-light irradiation
      (lambda > 620 nm). The photocatalytic abilities were affected by the phosphine
      ligands on the Re unit, and the supramolecule with P(p-Cl-C6H4)3 ligands
      exhibited better photocatalysis (PhiCO = 0.12, TONCO = 1138, TOFCO = 3.3 min(
      1)). The detailed studies clarified the electron balance and material balance;
      i.e., one molecule of the sacrificial electron donor (1,3-dimethyl-2-phenyl-2,3
      dihydro-1H-benzo[d]imidazole (BIH)) donated two electrons, one molecule of CO2
      accepted the two electrons, and another CO2 molecule served as an "O(2-)"
      acceptor to give each molecule of the two-electron oxidized compound of BIH, CO,
      and HCO3(-). 

PMID- 24083378
TI  - Dissociation of a strong acid in neat solvents: diffusion is observed after
      reversible proton ejection inside the solvent shell.
AB  - Strong-acid dissociation was studied in alcohols. Optical excitation of the
      cationic photoacid N-methyl-6-hydroxyquinolinium triggers proton transfer to the
      solvent, which was probed by spectral reconstruction of picosecond fluorescence
      traces. The process fulfills the classical Eigen-Weller mechanism in two stages:
      (a) solvent-controlled reversible dissociation inside the solvent shell and (b)
      barrierless splitting of the encounter complex. This can be appreciated only when
      fluorescence band integrals are used to monitor the time evolution of the
      reactant and product concentrations. Band integrals are insensitive to solvent
      dynamics and report relative concentrations directly. This was demonstrated by
      first measuring the fluorescence decay of the conjugate base across the full
      emission band, independently of the proton-transfer reaction. Multiexponential
      decay curves at single wavelengths result from a dynamic red shift of
      fluorescence in the course of solvent relaxation, whereas clean single
      exponential decays are obtained if the band integral is monitored instead. The
      extent of the shift is consistent with previously reported femtosecond transient
      absorption measurements, continuum theory of solvatochromism, and molecular
      properties derived from quantum chemical calculations. In turn, band integrals
      show clean biexponential decay of the photoacid and triexponential evolution of
      the conjugate base in the course of the proton transfer to solvent reaction. The
      dissociation step follows the slowest stage of solvation, which was measured here
      independently by picosecond fluorescence spectroscopy in five aliphatic alcohols.
      Also, the rate constant of the encounter-complex splitting stage is compatible
      with proton diffusion. Thus, for this photoacid, both stages reach the highest
      possible rates: solvation and diffusion control. Under these conditions, the
      concentration of the encounter complex is substantial during the earliest
      nanosecond. 

PMID- 24083377
TI  - A polymeric fastener can easily functionalize liposome surfaces with gadolinium
      for enhanced magnetic resonance imaging.
AB  - Common methods of loading magnetic resonance imaging (MRI) contrast agents into
      nanoparticles often suffer from challenges related to particle formation, complex
      chemical modification/purification steps, and reduced contrast efficiency. This
      study presents a simple, yet advanced process to address these issues by loading
      gadolinium, an MRI contrast agent, exclusively on a liposome surface using a
      polymeric fastener. The fastener, so named for its ability to physically link the
      two functional components together, consisted of chitosan substituted with
      diethylenetriaminepentaacetic acid (DTPA) to chelate gadolinium, as well as
      octadecyl chains to stabilize the modified chitosan on the liposome surface. The
      assembly strategy, mimicking the mechanisms by which viruses and proteins
      naturally anchor to a cell, provided greater T1 relaxivity than liposomes loaded
      with gadolinium in both the interior and outer leaflet. Gadolinium-coated
      liposomes were ultimately evaluated in vivo using murine ischemia models to
      highlight the diagnostic capability of the system. Taken together, this process
      decouples particle assembly and functionalization and, therefore, has
      considerable potential to enhance imaging quality while alleviating many of the
      difficulties associated with multifunctional particle fabrication. 

PMID- 24083379
TI  - Secondhand tobacco smoke exposure and heart rate variability and inflammation
      among non-smoking construction workers: a repeated measures study.
AB  - BACKGROUND: Although it has been well recognized that exposure to secondhand
      tobacco smoke (SHS) is associated with cardiovascular mortality, the mechanisms
      and time course by which SHS exposure may lead to cardiovascular effects are
      still being explored. METHODS: Non-smoking workers were recruited from a local
      union and monitored inside a union hall while exposed to SHS over approximately 6
      hours. Participants were fitted with a continuous electrocardiographic monitor
      upon enrollment which was removed at the end of a 24-hr monitoring period. A
      repeated measures study design was used where resting ECGs and blood samples were
      taken from individuals before SHS exposure (baseline), immediately following SHS
      exposure (post) and the morning following SHS exposure (next
      morning).Inflammatory markers, including high sensitivity C-reactive protein
      (CRP) and white blood cell count (WBC) were analyzed. Heart rate variability
      (HRV) was analyzed from the ECG recordings in time (SDNN, rMSSD) and frequency
      (LF, HF) domain parameters over 5-minute periods. SHS exposure was quantified
      using a personal fine particulate matter (PM2.5) monitor.Linear mixed effects
      regression models were used to examine within-person changes in inflammatory and
      HRV parameters across the 3 time periods. Exposure-response relationships with
      PM2.5 were examined using mixed effects models. All models were adjusted for age,
      BMI and circadian variation. RESULTS: A total of 32 male non-smokers were
      monitored between June 2010 and June 2012. The mean PM2.5 from SHS exposure was
      132 MUg/m3. Immediately following SHS exposure, a 100 MUg/m3 increase in PM2.5
      was associated with declines in HRV (7.8% [standard error (SE) =3%] SDNN, 8.0%
      (SE = 3.9%) rMSSD, 17.2% (SE = 6.3%) LF, 29.0% (SE = 10.1%) HF) and increases in
      WBC count 0.42 (SE = 0.14) k/MUl. Eighteen hours following SHS exposure, a 100
      MUg/m3 increase in PM2.5 was associated with 24.2% higher CRP levels.
      CONCLUSIONS: Our study suggest that short-term SHS exposure is associated with
      significantly lower HRV and higher levels of inflammatory markers. Exposure
      associated declines in HRV were observed immediately following exposure while
      higher levels of CRP were not observed until 18 hours following exposure.
      Cardiovascular autonomic and inflammation responses may contribute to the
      pathophysiologic pathways that link SHS exposure with adverse cardiovascular
      outcomes.

PMID- 24083380
TI  - Differential PKA activation and AKAP association determines cell fate in cancer
      cells.
AB  - BACKGROUND: The dependence of malignant properties of colorectal cancer (CRC)
      cells on IGF1R signaling has been demonstrated and several IGF1R antagonists are
      currently in clinical trials. Recently, we identified a novel pathway in which
      cAMP independent PKA activation by TGFbeta signaling resulted in the
      destabilization of survivin/XIAP complex leading to increased cell death. In this
      study, we evaluated the effect of IGF1R inhibition or activation on PKA
      activation and its downstream cell survival signaling mechanisms. METHODS: Small
      molecule IGF1R kinase inhibitor OSI-906 was used to test the effect of IGF1R
      inhibition on PKA activation, AKAP association and its downstream cell survival
      signaling. In a complementary approach, ligand mediated activation of IGF1R was
      performed and AKAP/PKA signaling was analyzed for their downstream survival
      effects. RESULTS: We demonstrate that the inhibition of IGF1R in the IGF1R
      dependent CRC subset generates cell death through a novel mechanism involving
      TGFbeta stimulated cAMP independent PKA activity that leads to disruption of cell
      survival by survivin/XIAP mediated inhibition of caspase activity. Importantly,
      ligand mediated activation of the IGF1R in CRC cells results in the generation of
      cAMP dependent PKA activity that functions in cell survival by inhibiting caspase
      activity. Therefore, this subset of CRC demonstrates 2 opposing pathways
      organized by 2 different AKAPs in the cytoplasm that both utilize activation of
      PKA in a manner that leads to different outcomes with respect to life and death.
      The cAMP independent PKA activation pathway is dependent upon mitochondrial
      AKAP149 for its apoptotic functions. In contrast, Praja2 (Pja2), an AKAP-like E3
      ligase protein was identified as a key element in controlling cAMP dependent PKA
      activity and pro-survival signaling. Genetic manipulation of AKAP149 and Praja2
      using siRNA KD had opposing effects on PKA activity and survivin/XIAP regulation.
      CONCLUSIONS: We had identified 2 cytoplasmic pathways dependent upon the same
      enzymatic activity with opposite effects on cell fate in terms of life and death.
      Understanding the specific mechanistic functions of IGF1R with respect to
      determining the PKA survival functions would have potential for impact upon the
      development of new therapeutic strategies by exploiting the IGF1R/cAMP-PKA
      survival signaling in cancer.

PMID- 24083381
TI  - T-cell co-stimulatory blockade in transplantation: two steps forward one step
      back!
AB  - INTRODUCTION: The concern about nephrotoxicity with calcineurin inhibitors led to
      the search of novel agents for immunosuppression. Based on the requirement of T
      cell co-stimulatory signals to fully activated naive T cells, it became clear
      that blocking these pathways could be an appealing therapeutic target. However,
      some unexpected findings were noticed in the recent clinical trials of
      belatacept, including a higher rate of rejection, which warranted further
      investigation with some interesting concepts emerging from the bench. AREAS
      COVERED: This article aims to review the literature of the B7:CD28 co-stimulatory
      blockade in transplantation, including the basic immunology behind its
      development, clinical application and potential limitations. EXPERT OPINION:
      Targeting co-stimulatory pathways were found to be much more complex than
      initially anticipated due to the interplay between not only various co
      stimulatory pathways but also various co-inhibitory ones. In addition, co
      stimulatory signals have different roles in diverse immune cell types. Therefore,
      targeting CD28 ligands with cytotoxic T lymphocyte antigen-4 (CTLA4)-Ig may have
      some deleterious effects, including the inhibition of regulatory T cells,
      blockade of co-inhibitory signals (CTLA4) and promotion of Th17 cells. Co
      stimulatory independence of memory T cells was another unforeseen limitation.
      Learning how to better integrate co-stimulatory targeting with other
      immunosuppressive agents will be critical for the improvement of long-term graft
      survival.

PMID- 24083384
TI  - Dose-response approaches for nuclear receptor-mediated modes of action for liver
      carcinogenicity: Results of a workshop.
AB  - A public workshop, organized by a Steering Committee of scientists from
      government, industry, universities and research organizations, was held at the
      National Institute of Environmental Health Sciences (NIEHS) in September, 2010.
      The workshop explored the dose-response implications of toxicant modes of action
      (MOA) mediated by nuclear receptors. The dominant paradigm in human health risk
      assessment has been linear extrapolation without a threshold for cancer, and
      estimation of sub-threshold doses for non-cancer and (in appropriate cases)
      cancer endpoints. However, recent publications question the application of dose
      response modeling approaches with a threshold. The growing body of molecular
      toxicology information and computational toxicology tools has allowed for
      exploration of the presence or absence of sub-threshold doses for a number of
      receptor-mediated MOAs. The workshop explored the development of dose-response
      approaches for nuclear receptor-mediated liver cancer, within a MOA Human
      Relevance Framework (HRF). Case studies addressed activation of the AHR, the CAR
      and the PPARalpha. This article describes the workshop process, key issues
      discussed and conclusions. The value of an interactive workshop approach to apply
      current MOA/HRF frameworks was demonstrated. The results may help direct research
      on the MOA and dose-response of receptor-based toxicity, since there are
      commonalities for many receptors in the basic pathways involved for late steps in
      the MOA, and similar data gaps in early steps. Three additional papers in this
      series describe the results and conclusions for each case-study receptor
      regarding its MOA, relevance of the MOA to humans and the resulting dose-response
      implications.

PMID- 24083385
TI  - Hierarchy in Au nanocrystal ordering in a supracrystal: II. Control of
      interparticle distances.
AB  - Au nanocrystals coated with thiol derivatives differing by the length of their
      alkyl chains are used to build 3D superlattices called supracrystals. In this
      study, we used two sets of Au nanocrystals differing by their sizes and size
      distributions. The average sizes are 5 nm (Au5) and 7 nm (Au7). From one
      experiment to the other, the size distribution slightly changes. For Au5
      nanocrystals, it evolves from 6 to 8%, and for Au7 nanocrystals, it varies from 5
      to 6%. The Au nanocrystals (Au5 and Au7) are first dispersed in toluene and
      produce fcc supracrystals by solvent evaporation. Here, by small-angle grazing X
      ray diffraction, we observe a control in the average interparticle distance
      within the supracrystals. When the supracrystals are grown at zero toluene vapor
      pressure, the interparticle distances increase linearly with the alkyl chain
      length of the nanocrystals' coating agent regardless of their diameters.
      Furthermore, the dry supracrystals can swell and the interparticle distance
      within the superstructure be increased by subjecting the material to toluene
      vapor pressure after initial growth. This swelling process is reversible, and
      retraction occurs when the toluene vapor pressure drops. This indicates a strong
      ability of the dried supracrystals to trap toluene molecules. On increasing the
      toluene vapor pressure during the solvent evaporation process, the slope of the
      linear dependency of the interparticle distances to the alkyl chain length is
      markedly decreased and the interparticle distance reaches a quasi-plateau. This
      is explained by the influence of depletion forces created by the presence of
      thiol-containing molecules physisorbed on the coating molecules on the internal
      structure of these supracrystals. Recently, we demonstrated that, by using the
      same nanocrystals (Au5 and Au7), a hierarchy in the supracrystal growth process
      takes place from heterogeneous nucleation with the formation of a layer-by-layer
      film to homogeneous nucleation in solution with the formation of shaped
      supracrystals. Here it is shown that the interparticle distance is independent of
      the supracrystal growth mechanisms. 

PMID- 24083386
TI  - Association of inflammation with loss of ability to walk 400 meters: longitudinal
      findings from the Invecchiare in Chianti Study.
AB  - OBJECTIVES: To examine relationships between eight markers of inflammation
      (interleukin (IL)-6, IL-6 receptor (R), C-reactive protein (CRP), tumor necrosis
      factor (TNF)-alpha, TNF receptor 1 (R1), TNFR2, IL-1 receptor antagonist, IL-18)
      and incident loss of ability to walk 400 m. DESIGN: Prospective cohort study.
      SETTING: Older adults enrolled in the Invecchiare in Chianti Study. PARTICIPANTS:
      Community-dwelling participants aged 65 and older (N = 1,006). MEASUREMENTS: The
      eight inflammatory markers were measured at baseline, and an inflammation score
      was calculated based on the number of inflammatory markers for which the
      participant was in the highest quartile. Incidence of mobility disability was
      determined in participants able to walk 400 m at baseline. Logistic regression
      models were used to determine whether each of the inflammatory markers and the
      inflammation score predicted loss of the ability to walk 400 m at 6-year follow
      up. RESULTS: After adjusting for covariates, individuals with a TNFR1 level in
      each of the highest three quartiles (Q2, 3, 4) were more likely to be unable to
      walk 400 m at follow-up than those with TNFR1 levels in Q1. When adjusting for
      the same covariates, participants with an inflammation score of 3 or 4 were more
      likely to become unable to walk 400 m at follow-up than participants with a score
      of 0. CONCLUSION: These results provide additional evidence that inflammation is
      a factor in the mechanisms that cause incident mobility disability and suggest
      that a combined measure of inflammatory markers may improve prediction of
      functional prognosis.

PMID- 24083387
TI  - Efficient induction of pluripotent stem cells from granulosa cells by Oct4 and
      Sox2.
AB  - Various types of somatic cells can be reprogrammed to induced pluripotent stem
      (iPS) cells. Somatic stem cells exhibit enhanced reprogramming efficiency by
      fewer factors, in contrast to fully differentiated cells. Nuclear LaminA is
      highly expressed in differentiated cells, and stem cells are characterized by the
      absence of LaminA. Granulosa cells (GCs) and cumulus cells in the ovarian
      follicles effectively and firstly generated cloned mice by somatic cell nuclear
      transfer, and these cells lack LaminA expression. We tested the hypothesis that
      GCs could be effectively used to generate iPS cells with fewer factors. We show
      that iPS cells are generated from GCs at high efficiency even with only two
      factors, Oct4 and Sox2, like the iPS cells generated using four Yamanaka factors.
      These iPS cells show pluripotency in vitro and in vivo, as evidenced by high
      expression of pluripotency-associated genes, Oct4, Nanog, and SSEA-1,
      differentiation into three embryonic germ layers by embryoid body formation and
      teratoma tests, as well as high efficient generation of chimeras. Moreover, the
      exogenous genes are effectively silenced in these iPS cells. These data provide
      additional evidence in supporting the notion that reduced expression of LaminA
      and stem cells can improve the reprogramming efficiency to pluripotency.

PMID- 24083389
TI  - A novel antagonist of Toll-like receptors 7, 8 and 9 suppresses lupus disease
      associated parameters in NZBW/F1 mice.
AB  - Systemic Lupus Erythematosus is an autoimmune disease characterized by production
      of autoantibodies against nucleic acid-associated antigens. Endogenous DNA and
      RNA associated with these antigens stimulate inflammatory responses through Toll
      like receptors (TLRs) and exacerbate lupus disease pathology. We have evaluated
      an antagonist of TLR7, 8 and 9 as a therapeutic agent in lupus-prone NZBW/F1
      mice. NZBW/F1 mice treated with the antagonist had lower serum levels of
      autoantibodies targeting DNA, RNP, Smith antigen, SSA and SSB than did untreated
      mice. Reduction in blood urea nitrogen and proteinuria and improvements in kidney
      histopathology were observed in antagonist-treated mice. The antagonist treatment
      also reduced serum IL-12 and IL-1beta and increased IL-10 levels. Levels of mRNA
      for IL-6, iNOS and IL-1beta were lower in the kidneys and spleen of antagonist
      treated mice than in those of untreated mice. Levels of mRNA for IP-10, TNFRSF9
      and FASL were lower and IL-4 mRNA were higher in spleens of antagonist-treated
      mice than in spleens of untreated mice. mRNA for the inflammasome component NLRP3
      was lower and mRNA for the antioxidant enzymes, catalase and glutathione
      peroxidase 1 was higher in the kidneys of antagonist-treated mice than in those
      of untreated mice. These results show that the antagonist of TLR7, 8 and 9
      effectively inhibits inflammatory pathways involved in the development of lupus
      in NZBW/F1 mice and constitutes a potential therapeutic approach for the
      treatment of lupus and other autoimmune diseases.

PMID- 24083388
TI  - Genetic background modulates phenotypes of serotonin transporter Ala56 knock-in
      mice.
AB  - BACKGROUND: Previously, we identified multiple, rare serotonin (5-HT) transporter
      (SERT) variants in children with autism spectrum disorder (ASD). Although in our
      study the SERT Ala56 variant was over-transmitted to ASD probands, it was also
      seen in some unaffected individuals, suggesting that associated ASD risk is
      influenced by the epistatic effects of other genetic variation. Subsequently, we
      established that mice expressing the SERT Ala56 variant on a 129S6/S4 genetic
      background display multiple biochemical, physiological and behavioral changes,
      including hyperserotonemia, altered 5-HT receptor sensitivity, and altered
      social, communication, and repetitive behavior. Here we explore the effects of
      genetic background on SERT Ala56 knock-in phenotypes. METHODS: To explore the
      effects of genetic background, we backcrossed SERT Ala56 mice on the 129
      background into a C57BL/6 (B6) background to achieve congenic B6 SERT Ala56 mice,
      and assessed autism-relevant behavior, including sociability, ultrasonic
      vocalizations, and repetitive behavior in the home cage, as well as serotonergic
      phenotypes, including whole blood serotonin levels and serotonin receptor
      sensitivity. RESULTS: One consistent phenotype between the two strains was
      performance in the tube test for dominance, where mutant mice displayed a greater
      tendency to withdraw from a social encounter in a narrow tube as compared to
      wildtype littermate controls. On the B6 background, mutant pup ultrasonic
      vocalizations were significantly increased, in contrast to decreased
      vocalizations seen previously on the 129 background. Several phenotypes seen on
      the 129 background were reduced or absent when the mutation was placed on the B6
      background, including hyperserotonemia, 5-HT receptor hypersensivity, and
      repetitive behavior. CONCLUSIONS: Our findings provide a cogent example of how
      epistatic interactions can modulate the impact of functional genetic variation
      and suggest that some aspects of social behavior may be especially sensitive to
      changes in SERT function. Finally, these results provide a platform for the
      identification of genes that may modulate the risk of ASD in humans.

PMID- 24083390
TI  - Functional implications of IgG anti-endothelial cell antibodies in pulmonary
      arterial hypertension.
AB  - The objective of this study was to research the functionality of anti-endothelial
      cell antibodies (AECA) in pulmonary arterial hypertension (PAH) by assessing the
      effects of IgG from AECA-positive PAH patients on the induction of adhesion
      molecules on human umbilical vein endothelial cells (HUVECs) and on the
      production of pro-inflammatory cytokines and chemokines by HUVECs. To achieve
      this purified IgG from 28 PAH patients were included. IgG from systemic sclerosis
      (SSc) (n = 58) and systemic lupus erythematosus (SLE) (n = 16) patients without
      PAH were included as disease controls. Intercellular adhesion molecule-1 (ICAM
      1), vascular cell adhesion molecule-1 (VCAM-1) and E-selectin expression on
      HUVECs, incubated with patient IgG, were quantified by flow cytometry. Production
      of interleukin (IL)-1beta, -6, -8, and CC chemokine ligand 2 (CCL2) by HUVECs,
      incubated with patient IgG, were quantified by multiplex flow cytometry. Our
      results showed that IgG from AECA-positive PAH, SSc and SLE patients induced
      significantly higher expression of ICAM-1, VCAM-1, and E-selectin and production
      of IL-6, -8, and CCL2 compared to IgG from AECA-negative patients and IgG from
      healthy controls. Like in SLE and SSc, IgG from AECA-positive PAH patients can
      activate endothelial cells to a pro-adhesive and pro-inflammatory state.
      Therefore, IgG AECA could play a pathogenic role by inducing inflammatory injury
      of vascular endothelium which is considered a key player in the initiation and
      progression of PAH.

PMID- 24083391
TI  - Optical neuritis induced by different concentrations of myelin oligodendrocyte
      glycoprotein presents different profiles of the inflammatory process.
AB  - Optical neuritis (ON) is characterized by inflammation of the optic nerve, and is
      one of the first clinical signs of multiple sclerosis (MS). Experimental
      autoimmune encephalomyelitis (EAE) is the animal model used to study MS and ON.
      The present study evaluated the induction, development and progression of ON
      using an EAE model induced by 100 MUg or 300 MUg of MOG35-55. An EAE model was
      induced in C57BL/6 mice by tail base injection of 100 MUg or 300 MUg of MOG35-55
      in complete Freund's adjuvant, supplemented with Mycobacterium tuberculosis. On
      the day of injection and 48 h later, animals received intraperitoneally 300 ng of
      pertussis toxin. On days 7, 10, 14, 21 and 58 the optic nerve was dissected for
      histological analysis, production of CCL5 and immunohistochemical detection of
      CD4 and CD8. The histological changes observed in the optic nerves consisted of
      inflammatory cell infiltrates showing varying degrees of ON in the two groups.
      The onset of ON in the 300 MUg of MOG35-55 group was coincident with higher
      production of CCL5, on day 10 after induction. However, the 100 MUg MOG35-55
      group showed more intense inflammatory infiltrate on day 14 after induction, with
      higher amounts of CD4 and CD8, reaching an excessive demyelination process on
      days 21 and 58 after induction. The results suggest that two different
      concentrations of MOG35-55 lead to different forms of evolution of optic
      neuritis.

PMID- 24083392
TI  - Vitamin D insufficiency and deficiency with stages of chronic kidney disease in
      an Asian population.
AB  - BACKGROUND: Vitamin D insufficiency is associated with proteinuria and could be a
      risk factor for end-stage renal disease (ESRD). However, few studies have
      examined the significance of vitamin D insufficiency as a contributing factor for
      the development of ESRD in the Asian chronic kidney disease (CKD) population.
      METHODS: Authors examined the relationship between vitamin D status and the
      staging of CKD using data from an outpatient clinic-based screening in 2,895 Thai
      CKD patients. Serum levels of 25-hydroxyvitamin D were analyzed according to CKD
      stages. Vitamin D deficiency and insufficiency were defined as a serum 25
      hydroxyvitamin D concentration < 10 ng/mL and 10-30 ng/mL, respectively. RESULTS:
      The mean (SD) 25-hydroxyvitamin D levels were significantly lower according to
      severity of renal impairment (CKD stage 3a: 27.84 +/- 14.03 ng/mL, CKD stage 3b:
      25.86 +/- 11.14 ng/mL, CKD stage 4: 24.09 +/- 11.65 and CKD stage 5: 20.82 +/-
      9.86 ng/mL, p<0.001). The prevalence of vitamin D deficiency/insufficiency was
      from CKD stage 3a, 3b, 4 to 5, 66.6%, 70.9%, 74.6%, and 84.7% (p<0.001). The odds
      ratio (95% CI) of vitamin D insufficiency/deficiency (serum 25-hydroxyvitamin D
      <= 30 ng/mL) and vitamin D deficiency (serum 25-hydroxyvitamin D < 10 ng/mL) for
      developing ESRD, after adjustment for age, gender, hemoglobin, serum albumin,
      calcium, phosphate and alkaline phosphatase were 2.19 (95% CI 1.07 to 4.48) and
      16.76 (95% CI 4.89 to 57.49), respectively. CONCLUSION: This study demonstrates
      that 25-hydroxyvitamin D insufficiency and deficiency are more common and
      associated with the level of kidney function in the Thai CKD population
      especially advanced stage of CKD.

PMID- 24083393
TI  - Protective effect of the omega-3 polyunsaturated fatty acids: Eicosapentaenoic
      acid/Docosahexaenoic acid 1:1 ratio on cardiovascular disease risk markers in
      rats.
AB  - BACKGROUND: High consumption of fish carries a lower risk of cardiovascular
      disease as a consequence of dietary omega-3 long chain polyunsaturated fatty acid
      (n-3 PUFA; especially EPA and DHA) content. A controversy exists about the
      component/s responsible of these beneficial effects and, in consequence, which is
      the best proportion between both fatty acids. We sought to determine, in healthy
      Wistar rats, the proportions of EPA and DHA that would induce beneficial effects
      on biomarkers of oxidative stress, and cardiovascular disease risk. METHODS:
      Female Wistar rats were fed for 13 weeks with 5 different dietary supplements of
      oils; 3 derived from fish (EPA/DHA ratios of 1:1, 2:1, 1:2) plus soybean and
      linseed as controls. The activities of major antioxidant enzymes (SOD, CAT, GPX,
      and GR) were determined in erythrocytes and liver, and the ORAC test was used to
      determine the antioxidant capacity in plasma. Also measured were: C reactive
      protein (CRP), endothelial dysfunction (sVCAM and sICAM), prothrombotic activity
      (PAI-1), lipid profile (triglycerides, cholesterol, HDLc, LDLc, Apo-A1, and Apo
      B100), glycated haemoglobin and lipid peroxidation (LDL-ox and MDA values).
      RESULTS: After three months of nutritional intervention, we observed
      statistically significant differences in the ApoB100/ApoA1 ratio, glycated
      haemoglobin, VCAM-1, SOD and GPx in erythrocytes, ORAC values and LDL-ox.
      Supplementation with fish oil derived omega-3 PUFA increased VCAM-1, LDL-ox and
      plasma antioxidant capacity (ORAC). Conversely, the ApoB100/ApoA1 ratio and
      percentage glycated haemoglobin decreased. CONCLUSIONS: Our results showed that a
      diet of a 1:1 ratio of EPA/DHA improved many of the oxidative stress parameters
      (SOD and GPx in erythrocytes), plasma antioxidant capacity (ORAC) and
      cardiovascular risk factors (glycated haemoglobin) relative to the other diets.

PMID- 24083394
TI  - Explaining the effects of anticipated regret messages on young women's intention
      to consume folic acid: a moderated-mediation model.
AB  - This study tests a moderated-mediation model to explain the joint effects of
      consideration of future consequences and exposure to health messages containing
      an anticipated regret component on behavioral intention to consume folic acid. In
      an online survey-experiment conducted in March 2011, 245 women 18-35 years of age
      were randomized to 1 of 3 conditions (exposure to attitude-only message/exposure
      to attitude-plus-anticipated-regret message/no message exposure) in a between
      participants design. Results showed a positive joint effect of consideration of
      future consequences and exposure to an attitude-plus-anticipated-regret message
      on anticipated regret (B = 0.89, SE = 0.41, p < .05). Among women high in
      consideration of future consequences, exposure to an attitude-plus-anticipated
      regret message increased anticipated regret. Likewise, another positive joint
      effect of consideration of future consequences and anticipated regret on
      behavioral intention was observed (B = 0.28, SE = 0.12, p < .05). Anticipated
      regret was positively related to intention among women high in consideration of
      future consequences. Implications are discussed. 

PMID- 24083395
TI  - Polymer and small molecule mixture for organic hole transport layers in quantum
      dot light-emitting diodes.
AB  - The performance of quantum dot light-emitting diodes (QD-LEDs) was investigated
      for different hole transport layers with small molecules and polymers: poly(4
      butyl-phenyl-diphenyl-amine), poly-N-vinylcarbazole (PVK), N,N'-diphenyl-N,N'
      bis(3-methylphenyl)-1,1'-diphenyl-4,4'-diamine, 4,4',4"-tris(N-carbazolyl)
      triphenyl-amine (TCTA), and 4,4'-bis(carbazole-9-yl)biphenyl (CBP). The
      electroluminescence performance of QD-LEDs was considerably improved by adding
      small molecules (TCTA or CBP) having high hole mobilily to the polymer hole
      transport material (PVK). The maximal current efficiency of QD-LED-based PVK was
      improved by 27% upon addition of 20 wt % TCTA due to the hole injection
      improvement. The lower turn-on voltage, the higher current density, and the
      higher luminance were achieved by addition of TCTA. The maximal luminance of
      40900 cd/m(2) and the highest current efficiency of 14.0 cd/A with the narrow
      full width at half-maximum (<35 nm) were achieved by the best hole transport
      layer. 

PMID- 24083396
TI  - The distribution, clearance, and safety of an anti-MMP-9 DNAzyme in normal and
      MMTV-PyMT transgenic mice.
AB  - Catalytic oligonucleotides, known as DNAzymes, are a new class of nucleic acid
      based gene therapy that have recently been used in preclinical animal studies to
      treat various cancers. In this study the systemic distribution, pharmacokinetics,
      and safety of intravenously administered anti-MMP (matrix metalloproteinase)-9
      DNAzyme (AM9D) were determined in healthy FVB and in MMTV-polyoma virus middle T
      (PyMT) transgenic mice bearing mammary tumors. MMP-9 is known to be involved in
      tumor cell development, angiogenesis, invasion, and metastasis. Sulfur-35 ((35)S)
      labeled ([(35)S]-AM9D) administered intravenously, without the use of carrier
      molecules, to healthy and mammary tumor bearing MMTV-PyMT transgenic mice
      distributed to all major organs. The order of percentages of [(35)S]-AM9D
      accumulation in different organs of healthy and MMTV-PyMT mice were
      blood>liver>kidney>lung>spleen>heart and mammary
      tumor>blood~liver>kidney>spleen>lung>heart, respectively. The amount of AM9D
      accumulated in mammary tumors 2 hours post injection was 0.6% and 0.2% higher
      than in either blood or liver, respectively, and its rate of initial clearance
      from mammary tissue was at least 50% slower than the other organs. Approximately
      43% of the delivered dosage of [(35)S]-AM9D was cleared from the system via feces
      and urine over a period of 72 hours. No evidence of acute or chronic
      cytotoxicity, local or widespread, associated with AM9D treatment (up to 75 mg
      AM9D /kg of body weight) was observed in the organs examined. These data suggest
      that DNAzyme in general and AM9D in particular can be used systemically as a
      therapeutic agent to treat patients with breast cancer or other metastatic and
      surgically inaccessible tumors.

PMID- 24083398
TI  - Abstracts of the 31st World Congress of Endourology. October 22-25, 2013.

PMID- 24083397
TI  - Human usage in the native range may determine future genetic structure of an
      invasion: insights from Acacia pycnantha.
AB  - BACKGROUND: The influence of introduction history and post-introduction dynamics
      on genetic diversity and structure has been a major research focus in invasion
      biology. However, genetic diversity and structure in the invasive range can also
      be affected by human-mediated processes in the native range prior to species
      introductions, an aspect often neglected in invasion biology. Here we aim to
      trace the native provenance of the invasive tree Acacia pycnantha by comparing
      the genetic diversity and structure between populations in the native Australian
      range and the invasive range in South Africa. This approach also allowed us to
      explore how human actions altered genetic structure before and after the
      introduction of A. pycnantha into South Africa. We hypothesized that extensive
      movement and replanting in A. pycnantha's Australian range prior to its
      introduction to South Africa might result in highly admixed genotypes in the
      introduced range, comparable genetic diversity in both ranges, and therefore
      preclude an accurate determination of native provenance(s) of invasive
      populations. RESULTS: In the native range Bayesian assignment tests identified
      three genetic clusters with substantial admixture and could not clearly
      differentiate previously identified genetic entities, corroborating admixture as
      a result of replantings within Australia. Assignment tests that included invasive
      populations from South Africa indicated similar levels of admixture compared to
      Australian populations and a lack of genetic structure. Invasive populations of
      A. pycnantha in South Africa are as genetically diverse as native populations,
      and could not be assigned to particular native range regions. CONCLUSIONS: Our
      results indicate that the genetic structure of A. pycnantha in Australia has been
      greatly altered through various planting initiatives. Specifically, there is
      little geographic structure and high levels of admixture. While numerous
      introduction history scenarios may explain the levels of admixture observed in
      South Africa, planting records of A. pycnantha in Australia suggest that
      populations were probably already admixed before propagules were introduced to
      South Africa. These findings have important implications for the management of
      invasive A. pycnantha populations in South Africa, especially for classical
      biological control, and more broadly, for studies that aim to understand the
      evolutionary dynamics of the invasion process.

PMID- 24083399
TI  - Raman activated cell ejection for isolation of single cells.
AB  - We have optimized a Raman microscope to obtain a single cell Raman spectrum
      (SCRS) with 0.1 s acquisition time. SCRS with such short acquisition time has
      sufficient discriminatory ability and spectral reproducibility to differentiate
      cells incorporated with (13)C and (15)N and to classify five different types of
      bacteria isolated from the oral cavity. We also developed Raman activated cell
      ejection (RACE) that is assisted by laser induced forward transfer (LIFT). We
      have shown, for the first time, that the single cells of interest can be
      identified and then accurately isolated from complex microbial communities based
      on their SCRS. This approach can be used to sort single cells of target traits
      from complex samples (e.g., biofilms, soils, sludge, tissues). 

PMID- 24083400
TI  - An evaluation of the PacBio RS platform for sequencing and de novo assembly of a
      chloroplast genome.
AB  - BACKGROUND: Second generation sequencing has permitted detailed sequence
      characterisation at the whole genome level of a growing number of non-model
      organisms, but the data produced have short read-lengths and biased genome
      coverage leading to fragmented genome assemblies. The PacBio RS long-read
      sequencing platform offers the promise of increased read length and unbiased
      genome coverage and thus the potential to produce genome sequence data of a
      finished quality containing fewer gaps and longer contigs. However, these
      advantages come at a much greater cost per nucleotide and with a perceived
      increase in error-rate. In this investigation, we evaluated the performance of
      the PacBio RS sequencing platform through the sequencing and de novo assembly of
      the Potentilla micrantha chloroplast genome. RESULTS: Following error-correction,
      a total of 28,638 PacBio RS reads were recovered with a mean read length of 1,902
      bp totalling 54,492,250 nucleotides and representing an average depth of coverage
      of 320* the chloroplast genome. The dataset covered the entire 154,959 bp of the
      chloroplast genome in a single contig (100% coverage) compared to seven contigs
      (90.59% coverage) recovered from an Illumina data, and revealed no bias in
      coverage of GC rich regions. Post-assembly the data were largely concordant with
      the Illumina data generated and allowed 187 ambiguities in the Illumina data to
      be resolved. The additional read length also permitted small differences in the
      two inverted repeat regions to be assigned unambiguously. CONCLUSIONS: This is
      the first report to our knowledge of a chloroplast genome assembled de novo using
      PacBio sequence data. The PacBio RS data generated here were assembled into a
      single large contig spanning the P. micrantha chloroplast genome, with a higher
      degree of accuracy than an Illumina dataset generated at a much greater depth of
      coverage, due to longer read lengths and lower GC bias in the data. The results
      we present suggest PacBio data will be of immense utility for the development of
      genome sequence assemblies containing fewer unresolved gaps and ambiguities and a
      significantly smaller number of contigs than could be produced using short-read
      sequence data alone.

PMID- 24083401
TI  - FTIR spectroscopy of NO3: perturbation analysis of the nu3+nu4 state.
AB  - High-resolution Fourier transform infrared spectra of the 15NO3 nu3+nu4 and
      nu3+nu4-nu4 bands were observed in the 1472 and 1112 cm(-1) regions. Compared
      with the case of 14N species, large effects of perturbations were recognized in
      many rotational levels of the 15NO3 nu3+nu4 state, and it was found that the
      nu2+2nu4 state is responsible for the perturbation. Although a direct Coriolis
      interaction (Deltanu2 = 1, Deltanu3(or Deltanu4)=1) is not present between these
      two vibrational levels, anharmonic terms including Phi344 and Phi444 mix nu3+nu4
      and 3nu4, nu2+2nu4, and nu2+2nu4 mixes with nu2+nu4 to produce Coriolis
      interaction between nu3+nu4 and nu2+2nu4. An analysis gave the energy difference
      of 7.274 cm(-1) between two levels, and interaction parameters were determined.
      Similar perturbation analysis was applied for the 14N species, and the previous
      (p)P(N,K) assignment of the nu3+nu4 A'-nu4 E' band was changed for giving one A2'
      state. Spectral lines to another A1' state were not assigned because of weak
      intensity, which is explained by intensity anomaly through vibronic interaction,
      reflecting the transition moment of the B2E'-X2A2' electronic band.

PMID- 24083402
TI  - Deferasirox for the treatment of iron overload in non-transfusion-dependent
      thalassemia.
AB  - Non-transfusion-dependent thalassemia (NTDT) defines a group of patients who do
      not require regular transfusions for survival, but are at significant risk of
      iron accumulation from underlying disease-related mechanisms distinct from
      transfusional iron overload. Management of iron overload in NTDT has received
      little attention compared with that of beta-thalassemia major, despite evidence
      of significant iron-induced complications with advancing age. The efficacy and
      safety of the iron chelator deferasirox in NTDT has been evaluated in two pilot
      studies and the first prospective, randomized, placebo-controlled study
      (THALASSA) of any chelator in NTDT. Treatment with deferasirox for up to 2 years
      yielded a sustained reduction in iron burden, with a clinically manageable safety
      profile. Following these trial data, deferasirox is the first iron chelator
      approved for use in NTDT patients, and with NTDT guidelines now available,
      physicians are better equipped to achieve effective monitoring and management of
      iron burden in NTDT. 

PMID- 24083403
TI  - Outcomes of feeding problems in advanced dementia in a nursing home population.
AB  - OBJECTIVES: To describe quality of care for feeding problems in advanced dementia
      and probability and predictors of weight loss and mortality. DESIGN: Prospective
      cohort. SETTING: Twenty-four nursing homes (NHs). PARTICIPANTS: Nursing home
      residents with advanced dementia and feeding problems and family surrogates (N =
      256). MEASUREMENTS: Family reported on quality of feeding care at enrollment and
      3 months. Chart reviews at enrollment and 3, 6, and 9 months provided data on
      feeding problems, treatments, weight loss of more than 5% in 30 days or more than
      10% in 6 months, and mortality. Organizational variables were obtained from
      administrator surveys and publically reported data. RESULTS: Residents with
      advanced dementia and feeding problems had an average age of 85; 80% had chewing
      and swallowing problems, 11% weight loss, and 48% poor intake. Family reported
      feeding assistance of moderate quality; 23% felt the resident received less
      assistance than needed. Mortality risk was significant; 8% died within 3 months,
      17% within 6 months, and 27% within 9 months. Residents with advanced dementia
      who had stable weight over 3 months had a 5.4% rate of significant weight loss
      and a 2.1% risk of death over the next 3 months. Residents with advanced dementia
      and weight loss over 3 months had a 38.9% chance of stabilizing weight over the
      next 3 months but also had a 19.2% chance of dying. Weight loss was the only
      independent predictor of death. CONCLUSION: Weight loss is a predictor of death
      in advanced dementia. Treatments can often stabilize weight, but weight loss
      should be used to trigger discussion of goals of care and treatment options.

PMID- 24083404
TI  - Control of mRNA stability contributes to low levels of nuclear poly(A) binding
      protein 1 (PABPN1) in skeletal muscle.
AB  - BACKGROUND: The nuclear poly(A) binding protein 1 (PABPN1) is a ubiquitously
      expressed protein that plays critical roles at multiple steps in post
      transcriptional regulation of gene expression. Short expansions of the
      polyalanine tract in the N-terminus of PABPN1 lead to oculopharyngeal muscular
      dystrophy (OPMD), which is an adult onset disease characterized by eyelid
      drooping, difficulty in swallowing, and weakness in the proximal limb muscles.
      Why alanine-expanded PABPN1 leads to muscle-specific pathology is unknown. Given
      the general function of PABPN1 in RNA metabolism, intrinsic characteristics of
      skeletal muscle may make this tissue susceptible to the effects of mutant PABPN1.
      METHODS: To begin to understand the muscle specificity of OPMD, we investigated
      the steady-state levels of PABPN1 in different tissues of humans and mice.
      Additionally, we analyzed the levels of PABPN1 during muscle regeneration after
      injury in mice. Furthermore, we assessed the dynamics of PABPN1 mRNA decay in
      skeletal muscle compared to kidney. RESULTS: Here, we show that the steady-state
      levels of both PABPN1 mRNA and protein are drastically lower in mouse and human
      skeletal muscle, particularly those impacted in OPMD, compared to other tissues.
      In contrast, PABPN1 levels are increased during muscle regeneration, suggesting a
      greater requirement for PABPN1 function during tissue repair. Further analysis
      indicates that modulation of PABPN1 expression is likely due to post
      transcriptional mechanisms acting at the level of mRNA stability. CONCLUSIONS:
      Our results demonstrate that PABPN1 steady-state levels and likely control of
      expression differ significantly in skeletal muscle as compared to other tissues,
      which could have important implications for understanding the muscle-specific
      nature of OPMD.

PMID- 24083407
TI  - Effects of physical activity on the development and progression of microvascular
      complications in type 1 diabetes: retrospective analysis of the DCCT study.
AB  - BACKGROUND: To examine the effects of physical activity on the development and
      progression of microvascular complications in patients with type 1 diabetes.
      METHODS: A retrospective analysis of data from the Diabetes Control and
      Complications trial was undertaken. Physical activity data was collected at
      baseline for each of 1441 recruits, converted to metabolic equivalent of task
      values, and categorised according to the American College of Sports Medicine
      recommendations. The rates of development/progression of diabetic retinopathy,
      nephropathy and neuropathy were compared in those who achieved over twice
      recommended, up to twice recommended, and less than recommended metabolic
      equivalent of task levels of activity. The DCCT study had a mean duration of
      follow up of 6.5 years ending in 1993. RESULTS: A total of 271 subjects had a
      sustained three-step progression in diabetic retinopathy. The rates of
      development or progression of retinopathy showed no significant association with
      physical activity level. The number of outcomes for nephropathy and neuropathy
      were small and there was no significant association with physical activity level.
      CONCLUSIONS: We found no evidence that physical activity improves microvascular
      outcomes in type 1 diabetes. However we demonstrate no evidence of harm. We
      suggest that physical activity continues to play an important role in the
      management of type 1 diabetes.

PMID- 24083409
TI  - Quaternary Zn-Ag-In-Se quantum dots for biomedical optical imaging of RGD
      modified micelles.
AB  - Exploring the synthesis of new biocompatible quantum dots (QDs) helps in
      overcoming the intrinsic toxicity of the existing QDs composed of highly toxic
      heavy metals (e.g., Cd, Hg, Pb, etc.) and is particularly interesting for the
      future practical application of QDs in biomedical imaging. Hence, in this report,
      a new one-pot approach to oil-soluble (highly toxic heavy metal-free) highly
      luminescent quaternary Zn-Ag-In-Se (ZAISe) QDs was designed. Their
      photoluminescence (PL) emission could be systematically tuned from 660 to 800 nm
      by controlling the Ag/Zn feed ratio, and their highest PL quantum yield is close
      to 50% after detailed optimization. Next, by using biodegradable RGD peptide
      (arginine-glycine-aspartic acid)-modified N-succinyl-N'-octyl-chitosan (RGD-SOC)
      micelles as a water transfer agent, the versatility of these quaternary ZAISe QDs
      for multiscale bioimaging of micelles (namely, in vitro and in vivo evaluating
      the tumor targeting of drug carriers) was further explored, as a promising
      alternative for Cd- and Pb-based QDs. 

PMID- 24083408
TI  - Structural and cognitive deficits in chronic carbon monoxide intoxication: a
      voxel-based morphometry study.
AB  - BACKGROUND: Patients with carbon monoxide (CO) intoxication may develop ongoing
      neurological and psychiatric symptoms that ebb and flow, a condition often called
      delayed encephalopathy (DE). The association between morphologic changes in the
      brain and neuropsychological deficits in DE is poorly understood. METHODS:
      Magnetic resonance imaging and neuropsychological tests were conducted on 11 CO
      patients with DE, 11 patients without DE, and 15 age-, sex-, and education
      matched healthy subjects. Differences in gray matter volume (GMV) between the
      subgroups were assessed and further correlated with diminished cognitive
      functioning. RESULTS: As a group, the patients had lower regional GMV compared to
      controls in the following regions: basal ganglia, left claustrum, right amygdala,
      left hippocampus, parietal lobes, and left frontal lobe. The reduced GMV in the
      bilateral basal ganglia, left post-central gyrus, and left hippocampus correlated
      with decreased perceptual organization and processing speed function. Those CO
      patients characterized by DE patients had a lower GMV in the left anterior
      cingulate and right amygdala, as well as lower levels of cognitive function, than
      the non-DE patients. CONCLUSIONS: Patients with CO intoxication in the chronic
      stage showed a worse cognitive and morphologic outcome, especially those with DE.
      This study provides additional evidence of gray matter structural abnormalities
      in the pathophysiology of DE in chronic CO intoxicated patients.

PMID- 24083410
TI  - Photouncaging nanoparticles for MRI and fluorescence imaging in vitro and in
      vivo.
AB  - Multimodal and multifunctional nanomaterials are promising candidates for
      bioimaging and therapeutic applications in the nanomedicine settings. Here we
      report the preparation of photouncaging nanoparticles with fluorescence and
      magnetic modalities and evaluation of their potentials for in vitro and in vivo
      bioimaging. Photoactivation of such bimodal nanoparticles prepared using
      photouncaging ligands, CdSe/ZnS quantum dots, and super paramagnetic iron oxide
      nanoparticles results in the systematic uncaging of the particles, which is
      correlated with continuous changes in the absorption, mass and NMR spectra of the
      ligands. Fluorescence and magnetic components of the bimodal nanoparticles are
      characterized using scanning electron microscopy (SEM), transmission electron
      microscopy (TEM), and elemental analyses using energy dispersive X-ray (EDX)
      spectroscopy and X-ray photoelectron spectroscopy (XPS). Bioconjugation of the
      nanoparticles with peptide hormones renders them with biocompatibility and
      efficient intracellular transport as seen in the fluorescence and MRI images of
      mouse melanoma cells (B16) or human lung epithelial adenocarcinoma cells (H1650).
      Biocompatibility of the nanoparticles is evaluated using MTT cytotoxicity assays,
      which show cell viability over 90%. Further, we combine MRI and NIR fluorescence
      imaging in C57BL/6 (B6) mice subcutaneously or intravenously injected with the
      photouncaging nanoparticles and follow the in vivo fate of the nanoparticles.
      Interestingly, the intravenously injected nanoparticles initially accumulate in
      the liver within 30 min post injection and subsequently clear by the renal
      excretion within 48 h as seen in the time-dependent MRI and fluorescence images
      of the liver, urinary bladder, and urine samples. Photouncaging ligands such as
      the ones reported in this article are promising candidates for not only the site
      specific delivery of nanomaterials-based contrast agents and drugs but also the
      systematic uncaging and renal clearance of nanomaterials after the desired in
      vivo application. 

PMID- 24083411
TI  - Effects of novel human cathepsin S inhibitors on cell migration in human cancer
      cells.
AB  - Elevated cathepsin S (Cat S) level is correlated with higher migration ability in
      tumor cells. This study investigates the inhibitory effect of novel synthetic
      alpha-ketoamide compounds on cathepsin activity and cancer cell migration. The
      effect of several alpha-ketoamide compounds on the activity of recombinant
      cathepsins (Cat S, Cat L and Cat K) was examined. Two highly metastatic cancer
      cell lines were incubated with three Cat S-specific compounds (6n, 6 w and 6r) to
      analyze their effect on cellular Cat S activity and cell migration. At a 100 nM
      concentration, compounds 6n, 6r and 6 w effectively inhibited Cat S activity. Cat
      S activity and cell migration were significantly reduced in CL1-3 cells after
      treatment with either 6n or 6 w at 5 MUM. Similar results were also obtained when
      A2058 cells were treated with 6n. These results highlight the therapeutic
      potential of alpha-ketoamide compounds, especially 6n and 6 w, to prevent or
      delay cancer metastasis.

PMID- 24083412
TI  - Functional genetic polymorphisms of monocyte chemoattractant protein 1 and C-C
      chemokine receptor type 2 in ischemic stroke.
AB  - Recent findings indicated that monocyte chemoattractant protein 1 (MCP1) and its
      C-C chemokine receptor type 2 (CCR2) play a key role in ischemic stroke (IS)
      progression. This study was aimed at evaluating the potential association of the
      MCP1 gene (MCP1) rs1024611 (-2518 A>G) and CCR2 gene (CCR2) rs1799864 (V64I; 190
      G>A) functional single nucleotide polymorphisms (SNPs) with IS in the Armenian
      population. For the purpose of this study, genomic DNA samples of 100 patients
      with the first-episode IS and 115 healthy subjects (controls) were genotyped for
      the selected SNPs using a polymerase chain reaction with sequence-specific
      primers. The results obtained demonstrated that while the CCR2 rs1799864 SNP
      genotypes were equally distributed among patients and controls, the frequency and
      carriage rate of the of the MCP1 rs1024611*G minor allele were higher in
      patients. While a potential association between IS and CCR2 rs1799864 SNP was
      evaluated for the first time, the latest finding was in agreement with the
      earlier data reported for some other populations. In summary, this study revealed
      no association of CCR2 rs1799864 SNP with IS, and a positive association between
      G minor allele of MCP1 rs1024611 SNP and IS in the Armenian population. Based on
      the present and earlier reported data, we concluded that the minor G allele of
      the MCP1 rs1024611 SNP might be considered a risk factor for IS. 

PMID- 24083413
TI  - TEACCH-based group social skills training for children with high-functioning
      autism: a pilot randomized controlled trial.
AB  - BACKGROUND: Although social skills training programs for people with high
      functioning autism (HFA) are widely practiced, the standardization of curricula,
      the examination of clinical effectiveness, and the evaluation of the feasibility
      of future trials have yet to be done in Asian countries. To compensate for this
      problem, a Japanese pilot randomized controlled trial (RCT) of the Treatment and
      Education of Autistic and Related Communication Handicapped Children (TEACCH)
      based group social skills training for children with HFA and their mothers was
      conducted. METHODS: Eleven children with HFA, aged 5-6 years, and their mothers
      were randomly assigned to the TEACCH program (n=5) or a waiting-list control
      group (n=6). The program involved comprehensive group intervention and featured
      weekly 2-hour sessions, totaling 20 sessions over six months. The adaptive
      behaviors and social reciprocity of the children, parenting stress, and parent
      child interactions were assessed using the Strengths and Difficulties
      Questionnaire (SDQ), Parenting Stress Index (PSI), Beck depression inventory-II
      (BDI-II), and Interaction Rating Scale (IRS). RESULTS: Through this pilot trial,
      the intervention and evaluation of the program has been shaped. There were no
      dropouts from the program and the mothers' satisfaction was high. The outcome
      measurements improved more in the program group than in the control group, with
      moderate effect sizes (SDQ, 0.71; PSI, 0.58; BDI-II, 0.40; and IRS, 0.69). This
      pilot trial also implied that this program is more beneficial for high IQ
      children and mothers with low stress than for those who are not. CONCLUSION: We
      have standardized the TEACCH program, confirmed the feasibility of a future
      trial, and successfully estimated the positive effect size. These findings will
      contribute to a larger trial in the future and to forthcoming systematic reviews
      with meta-analyses. TRIAL REGISTRATION: UMIN000004560.

PMID- 24083415
TI  - In situ sequestration of hydrophobic organic contaminants in sediments under
      stagnant contact with activated carbon. 1. Column studies.
AB  - The effectiveness of activated carbon (AC) treatment to sequester hydrophobic
      organic contaminants in sediments under stagnant contact was comprehensively
      studied for the first time. Two years of column experiments were conducted to
      simulate field conditions with two study sediments contaminated with petroleum
      and polychlorinated biphenyls, respectively, and variations in AC-sediment
      contact times, initial AC mixing regimes and distribution, AC particle sizes, and
      pore-water flow. The benefit of AC treatment was gradually enhanced with time
      toward the end point of the treatment, where sorption equilibrium is established
      between sediment and AC. After two years of stagnant contact, the contaminant
      uptake in polyethylene passive samplers embedded in the columns was reduced by 95
      99% for polycyclic aromatic hydrocarbons and 93-97% for polychlorinated biphenyls
      with 5 and 4 wt % AC dose, respectively, when AC was initially applied by
      mechanical mixing. These results verify that AC treatment can effectively control
      the availability of hydrophobic organic contaminants under stagnant conditions
      within a reasonable time frame following an initial distribution of AC into the
      sediment. The effectiveness of AC treatment was strongly dependent on AC particle
      size and AC distribution, while the effect of AC initial mixing regimes and pore
      water flow was not pronounced. 

PMID- 24083416
TI  - A 3D iron(II)-based MOF with squashed cuboctahedral nanoscopic cages showing spin
      canted long-range antiferromagnetic ordering.
AB  - The reaction of dilithium squarate with Fe(II) perchlorate led to the formation
      of a new Fe(II)-based 3D MOF, [Fe3(OH)3(C4O4)(C4O4)0.5]n (1), with homoleptic
      squashed cuboctahedral cages. Complex 1 crystallizes in the monoclinic C2/c space
      group. Fe(II) centers in the complex are octahedrally coordinated by four
      squarate dianions in axial and equatorial positions and two hydroxyl groups in
      the remaining equatorial positions. The interesting structural feature of 1 is
      that the three-dimensional framework is an infinite extension of nanoscopic
      cuboctahedral cages. The framework also contains two types of voids; the larger
      hydrophobic ones are surrounded by aromatic squarate ligands, while the smaller
      ones are hydrophilic with hydroxyl groups on the surface connected by bifurcated
      hydrogen bonding interaction. A variable temperature magnetic study shows spin
      canted long-range antiferromagnetic ordering in the low temperature regime. 

PMID- 24083414
TI  - Microwave-accelerated surface modification of plasmonic gold thin films with self
      assembled monolayers of alkanethiols.
AB  - A rapid surface modification technique for the formation of self-assembled
      monolayers (SAMs) of alkanethiols on gold thin films using microwave heating in
      <10 min is reported. In this regard, SAMs of two model alkanethiols, 11
      mercaptoundecanoic acid (11-MUDA, to generate a hydrophilic surface) and
      undecanethiol (UDET, a hydrophobic surface), were successfully formed on gold
      thin films using selective microwave heating in (1) a semicontinuous fashion and
      (2) a continuous fashion at room temperature (24 h, control experiment, no
      microwave heating). The formation of SAMs of 11-MUDA and UDET was confirmed by
      contact angle measurements, Fourier transform infrared (FT-IR) spectroscopy, and
      X-ray photoelectron spectroscopy (XPS). The contact angles for water on SAMs
      formed by the selective microwave heating and conventional room temperature
      incubation technique (24 h) were measured to be similar for 11-MUDA and UDET. FT
      IR spectroscopy results confirmed that the internal structures of SAMs prepared
      using both microwave heating and room temperature were similar. XPS results
      revealed that the organic and sulfate contaminants found on bare gold thin films
      were replaced by SAMs after the surface modification process had been conducted
      using both microwave heating and room temperature. 

PMID- 24083417
TI  - Effects of scanning (routine health information exposure) on cancer screening and
      prevention behaviors in the general population.
AB  - Research on health information exposure focuses primarily on deliberate
      information-seeking behavior and its effects on health. By contrast, this study
      explores the complementary and perhaps more influential role of health
      information acquired through exposure to routinely used sources, called scanning.
      The authors hypothesized that scanning from nonmedical sources, both mediated and
      interpersonal, affects cancer screening and prevention decisions. The authors
      used a nationally representative longitudinal survey of 2,489 adults 40 to 70
      years of age to analyze the effects of scanning on 3 cancer screening behaviors
      (mammography, prostate-specific antigen [PSA], and colonoscopy) and 3 prevention
      behaviors (exercising, eating fruits and vegetables, and dieting to lose weight).
      After adjustment for baseline behaviors and covariates, scanning at baseline
      predicted weekly exercise days 1 year later as well as daily fruit and vegetable
      servings 1 year later for those whose consumption of fruits and vegetables was
      already higher at baseline. Also, among those reporting timely screening
      mammogram behavior at baseline, scanning predicted repeat mammography. Scanning
      was marginally predictive of PSA uptake among those not reporting a PSA at
      baseline. Although there were strong cross-sectional associations, scanning did
      not predict dieting or colonoscopy uptake in longitudinal analyses. These
      analyses provide substantial support for a claim that routine exposure to health
      content from nonmedical sources affects specific health behaviors. 

PMID- 24083418
TI  - Harm reduction approach in Egypt: the insight of injecting drug users.
AB  - BACKGROUND: Egypt has low HIV prevalence (below 0?02%) among the general
      population, mostly attributed to the conservative culture. The 2010 second round
      biological/behavioral surveillance survey (Bio-BSS) conducted in some
      governorates revealed concentrated epidemic among male injecting drug users
      (IDUs). METHODS: The current study aimed at exploring the perspective of IDUs
      regarding the HIV preventive efforts targeting them to provide relevant evidence
      based policy recommendations. The study included desk review, in-depth interviews
      with service providers and focus group discussions with IDUs of both sexes.
      RESULTS: The study described the current harm reduction interventions in Egypt
      and highlighted the insights of active IDUs and service providers interacting
      with them as regards their ability to address their needs and what they miss in
      these interventions and how IDUs perceive these interventions. CONCLUSION: The
      epidemiological reality of HIV infection in Egypt favors prioritizing efforts to
      the high risk groups rather than the general population. Hence, harm reduction
      should be at the core of interventions targeting HIV. The current study revealed
      that there is still a long way to go to enhance the role of these interventions
      in influencing a significant behavior change among target group.

PMID- 24083419
TI  - Practical management of patients with myelofibrosis receiving ruxolitinib.
AB  - Myelofibrosis (MF) is characterized by bone marrow fibrosis, progressive anemia
      and extramedullary hematopoiesis, primarily manifested as splenomegaly. Patients
      also experience debilitating constitutional symptoms, including sequelae of
      splenomegaly, night sweats and fatigue. Ruxolitinib (INC424, INCB18424, Jakafi,
      Jakavi), a JAK1 and JAK2 inhibitor, was approved in November 2011 by the US FDA
      for the treatment of intermediate- or high-risk MF, and more recently in Europe
      and Canada for the treatment of MF-related splenomegaly or symptoms. These
      approvals were based on data from two randomized Phase III studies: COMFORT-I
      randomized against placebo, and COMFORT-II randomized against best available
      therapy. In these studies, ruxolitinib rapidly improved multiple disease
      manifestations of MF, reducing splenomegaly and improving quality of life of
      patients and potentially prolonging survival. However, as with other
      chemotherapies, ruxolitinib therapy is associated with some adverse events, such
      as anemia and thrombocytopenia. The aims of this article are to provide a brief
      overview of ruxolitinib therapy, to discuss some common adverse events associated
      with ruxolitinib therapy and to provide clinical management recommendations to
      maximize patients' benefit from ruxolitinib. 

PMID- 24083421
TI  - SNPs in KIT and KITLG genes may be associated with oligospermia in Chinese
      population.
AB  - KIT/KITLG signaling system is crucial for spermatogenesis, which suggests that
      KIT and KITLG genes may be involved in spermatogenesis impairment and male
      infertility. To explore the possible association of KIT and KITLG genes with male
      infertility having spermatogenesis impairment, polymorphism distributions of SNP
      rs3819392 in KIT gene as well as rs995030 and rs4474514 in KITLG gene were
      investigated in 372 patients with idiopathic azoospermia or oligospermia and 205
      fertile controls. As a result, the significant differences in polymorphism
      distributions of SNP rs3819392 in KIT gene and rs4474514 in KITLG gene were
      observed between the patients with oligospermia and controls. The frequencies of
      allele G (94.2% versus 90.0% p = 0.022) and genotype GG (89.2% versus 82.0% p =
      0.042) in patients with oligospermia were significantly higher than those in
      controls at rs3819392 locus in KIT gene. In addition, the genotype CC of
      rs4474514 in KITLG (8.2% versus 3.4%, p = 0.034) also significantly increased in
      oligospermic patients in comparison to controls. These findings indicated that
      SNP rs3819392 in KIT gene and rs4474514 in KITLG gene may be associated with
      oligospermia, suggesting that polymorphism of KIT and KITLG genes may play a role
      in oligospermia.

PMID- 24083420
TI  - Structural characterization of gangliosides and glycolipids via ultraviolet
      photodissociation mass spectrometry.
AB  - Ultraviolet photodissociation (UVPD) mass spectrometry was used to characterize
      the structures of amphiphilic glycosphingolipids and gangliosides in comparison
      to collision induced dissociation (CID) and higher energy collision dissociation
      (HCD) in a high performance Orbitrap mass spectrometer. UVPD produced the widest
      array of fragment ions diagnostic for both the ceramide base and oligosaccharide
      moieties. CID and HCD generated mainly glycosidic B/Y and C/Z cleavages of the
      oligosaccharides moieties and very few informative fragments related to the
      hydrophobic ceramide base. Several unique cleavages at the sphingoid base and the
      fatty acid chain occurred upon UVPD, as well as a wider variety of cross ring
      cleavages (A/X ions), thus affording differentiation of isobaric gangliosides. An
      LC-UVPD-MS strategy allowed the elucidation of 27 gangliosides among five
      different classes. 

PMID- 24083422
TI  - Prognostic implications of changes in cardiac troponin I levels in patients with
      non-ST elevation acute coronary syndrome.
AB  - OBJECTIVE: Information is limited on the prognostic implications of cardiac
      troponin I (cTnI) changes during the first days of non-ST elevation acute
      coronary syndrome (NSTE-ACS). METHODS: High-sensitivity cTnI levels were measured
      at study inclusion and after 48 h in 1615 conservatively managed NSTE-ACS
      patients from the Global Use of Strategies To Open Occluded Coronary Arteries
      (GUSTO) IV trial. RESULTS: Patients with moderately increased cTnI levels and
      without a relevant decrease over time had a significantly raised mortality at 30
      days and 1 year. No relevant associations between cTnI changes and recurrent
      myocardial infarction were seen. CONCLUSION: The cTnI change is predictive for
      subsequent mortality in selected conservatively managed NSTE-ACS patients.

PMID- 24083423
TI  - Synaptophysin is involved in resetting of the mammalian circadian clock.
AB  - BACKGROUND: Mammals can adapt to changing light/dark conditions by advancing or
      delaying their circadian clock phase. Light pulses evoke changes in gene
      expression and neuronal activity in the suprachiasmatic nuclei (SCN), the central
      pacemaker of the circadian system. Alterations in neuronal activity are partially
      mediated by changes in synaptic vesicle (SV) fusion at the presynaptic membrane,
      which modulates release of neurotransmitters. METHODS: Male synaptophysin (Syp)
      knock-out and littermate control wild type mice were tested in an Aschoff type I
      resetting paradigm. Additionally, gene expression of cFos, Per1 and Per2 was
      assessed in the SCN. Finally, complexes between the synaptic vesicle proteins Syp
      and synaptobrevin (Syb) were studied in order to correlate behavior with protein
      complexes at synaptic vesicles. RESULTS: Here we show that mice lacking Syp, a
      modulator of neurotransmitter release, are defective in delaying clock phase. In
      contrast, clock phase advances as well as clock period are normal in Syp-/- knock
      out mice. This correlates with the formation of Syp/Syb complexes. CONCLUSIONS:
      Our findings suggest that Syp is involved specifically in the response to a
      nocturnal light pulse occurring in the early night. It appears that the SV
      component Syp is critically involved in the delay portion of the resetting
      mechanism of the circadian clock.

PMID- 24083424
TI  - Mini nutritional assessment as a useful method of predicting the development of
      pressure ulcers in elderly inpatients.
AB  - OBJECTIVES: To determine the usefulness of the Mini Nutritional Assessment (MNA)
      and plasma amino acid analysis in predicting the formation of pressure ulcers
      (PUs) in inpatients. DESIGN: Prospective, observational cohort study with a mean
      observation period of 62.2 +/- 86.4 days. SETTING: Intermediate and acute care
      wards of a hospital in rural Japan. PARTICIPANTS: Inpatients with an average age
      of 85.0 +/- 7.6 (N = 422). MEASUREMENTS: Mini Nutritional Assessment, Subjective
      Global Assessment (SGA), Braden Scale (PU prognostic score), PU formation, and
      biochemical analysis including plasma amino acid concentrations. RESULTS: PUs
      developed in 7.1% of participants. A MNA score of less than 8 was more sensitive
      than a rating of moderate or severe malnourishment on the SGA combined with a
      Braden Scale score of less than 15 in predicting future PUs. The area under the
      receiver operating characteristic curve (AUC) of the MNA was superior to that of
      the Braden Scale. The Braden Scale nutrition subscore had the lowest AUC of the
      six Braden Scale subscores. Individuals who developed PUs had significantly lower
      plasma arginine concentrations than those who did not. CONCLUSION: Mini
      Nutritional Assessment was able to predict the development of PUs. A MNA score of
      less than 8 performed better than the SGA, Braden Scale, and plasma arginine
      levels in predicting PU development. Although lower plasma arginine concentration
      at time of admission was associated with PU development, the AUC for arginine was
      not significantly different from 0.50. The findings from this prospective study
      support the use of nutritional assessment in inpatients to predict PU risk and
      target appropriate interventions.

PMID- 24083425
TI  - Age-dependent changes in the expression of regulatory cell surface ligands in
      activated human T-cells.
AB  - BACKGROUND: The immune system consists of multiple preformed and more specific
      adaptive immune responses, which are all subject to both positive and negative
      regulation. Programmed cell death protein 1 (PD-1) is a cell surface ligand
      implicated in the induction of anergy, Inducible T-cell Costimulator (ICOS) plays
      a stimulatory role in the development of both CD4+ and CD8+ T-cells, Cytotoxic T
      Lymphocyte Antigen 4 (CTLA-4) plays a role in inhibitory regulation of T-cell
      activity, and T cell immunoglobulin and mucin protein 3 (Tim-3) has been
      described as a negative regulatory molecule in CD4+ helper type 1 cells and CD8+
      cytotoxic type 1 cells. Each of these ligands is induced with T-cell activation
      allowing greater opportunity to have a regulatory role. RESULTS: Flow cytometry
      was used to quantitate the expression of PD-1, ICOS, CTLA-4 and Tim-3 in human T
      cells from geriatric and younger subjects both at baseline and after in vitro
      induction by mitogen. The magnitude of expression of the molecules increased
      significantly on activated blasts after mitogen stimulation compared to their
      baseline levels in resting cells. The increase in CTLA-4 expressing CD8+ T-cells
      was significantly higher after in vitro induction in older persons, while the
      increase in cells expressing Tim-3 and PD-1 was significantly reduced. In CD4+ T
      cells, a greater increase in CTLA-4 expressing cells in older persons was the
      only difference between the age groups. CONCLUSIONS: We found several significant
      changes in the older individuals in regulatory elements of the adaptive immune
      system that occur particularly after immune activation. These differences could
      have ramifications to autoimmunity as well as immunology against infection and
      tumors.

PMID- 24083426
TI  - Galectin-9 is a suppressor of T and B cells and predicts the immune modulatory
      potential of mesenchymal stromal cell preparations.
AB  - Therapeutic approaches using multipotent mesenchymal stromal cells (MSCs) are
      advancing in regenerative medicine, transplantation, and autoimmune diseases. The
      mechanisms behind MSC immune modulation are still poorly understood and the
      prediction of the immune modulatory potential of single MSC preparations remains
      a major challenge for possible clinical applications. Here, we highlight galectin
      9 (Gal-9) as a novel, important immune modulator expressed by MSCs, which is
      strongly upregulated upon activation of the cells by interferon-gamma (IFN
      gamma). Further, we demonstrate that Gal-9 is a major mediator of the anti
      proliferative and functional effects of MSCs not only on T cells but also on B
      cells. Here, Gal-9 and activated MSCs contribute to the suppression of antigen
      triggered immunoglobulin release. Moreover, we determined that Gal-9 expression
      could serve as a marker to predict a higher or lower immune modulatory potential
      of single cell preparations and therefore to distinguish the therapeutic potency
      of MSCs derived from different donors. Also in vivo co-administration of MSCs or
      murine Gal-9 resulted in significantly reduced IgG titers in mice immunized with
      human coagulation factor VIII (FVIII). In conclusion, Gal-9 acts as an immune
      modulator interfering with multiple cell types including B cells and Gal-9 may
      serve as a predictive indicator for clinical MSC therapy.

PMID- 24083427
TI  - Effect of phosphorus levels on the protein profiles of secreted protein and root
      surface protein of rice.
AB  - Plant roots are complicated organs that absorb water and nutrients from the soil.
      Roots also play an essential role in protecting plants from attack by soil
      pathogens and develop a beneficial role with some soil microorganisms. Plant
      derived rhizosphere proteins (e.g., root secretory proteins and root surface
      binding proteins) are considered to play important roles in developing mutual
      relationships in the rhizosphere. In the rhizosphere, where plant roots meet the
      surrounding environment, it has been suggested that root secretory protein and
      root surface binding protein are important factors. Furthermore, it is not known
      how the physiological status of the plant affects the profile of these proteins.
      In this study, rice plants were grown aseptically, with or without phosphorus
      nutrition, and proteins were obtained from root bathing solution (designated as
      root secretory proteins) and obtained using 0.2 M CaCl2 solution (designated as
      root surface binding proteins). The total number of identified proteins in the
      root bathing solution was 458, and the number of root surface binding proteins
      was 256. More than half of the proteins were observed in both fractions. Most of
      the proteins were categorized as either having signal peptides or no membrane
      transport helix sites. The functional categorization suggested that most of the
      proteins seemed to have secretory pathways and were involved in defense/disease
      related functions. These characteristics seem to be unique to rhizosphere
      proteins, and the latter might be part of the plants strategy to defeat pathogens
      in the soil. The low phosphorus treatment significantly increased the number of
      pathogenesis-related proteins in the root secretory proteins, whereas the change
      was small in the case of the root surface binding proteins. The results suggested
      that the roots are actively and selectively secreting protein into the
      rhizosphere. 

PMID- 24083428
TI  - Novel FabH inhibitors: an updated article literature review (July 2012 to June
      2013).
AB  - INTRODUCTION: Fatty acid biosynthesis is essential for the bacterial viability
      and growth. In recent years, beta-ketoacyl-acyl carrier protein synthase III
      (FabH) become an attractive new target, which catalyzes the first step of fatty
      acid biosynthesis, and FabH inhibitors could be potential candidates for
      antibacterial agents. In this review, recent advances in the research of FabH
      inhibitors are reviewed. AREAS COVERED: This updated review summarized new
      patents and articles publications on FabH inhibitors within July 2012 to June
      2013. EXPERT OPINION: The review gives the latest development in the area of FabH
      inhibitors which aim to solve the bacterial resistance. The potent antibacterial
      activities of the selected compounds are probably correlated to their FabH
      inhibitory. Molecular docking of the most potent compound in every kind of
      compounds against FabH was also reviewed to explore the binding mode of the
      compound at the active site.

PMID- 24083429
TI  - Tissue engineering and regenerative medicine: past, present, and future.
AB  - Tissue and organ repair still represents a clinical challenge. Tissue engineering
      and regenerative medicine (TERM) is an emerging field focused on the development
      of alternative therapies for tissue/organ repair. This highly multidisciplinary
      field, in which bioengineering and medicine merge, is based on integrative
      approaches using scaffolds, cell populations from different sources, growth
      factors, nanomedicine, gene therapy, and other techniques to overcome the
      limitations that currently exist in the clinics. Indeed, its overall objective is
      to induce the formation of new functional tissues, rather than just implanting
      spare parts. This chapter aims at introducing the reader to the concepts and
      techniques of TERM. It begins by explaining how TERM have evolved and merged into
      TERM, followed by a short overview of some of its key aspects such as the
      combinations of scaffolds with cells and nanomedicine, scaffold processing, and
      new paradigms of the use of stem cells for tissue repair/regeneration, which
      ultimately could represent the future of new therapeutic approaches specifically
      aimed at clinical applications. 

PMID- 24083430
TI  - Tissue engineering and peripheral nerve reconstruction: an overview.
AB  - Nerve repair is no more regarded as merely a matter of microsurgical
      reconstruction. To define this evolving reconstructive/regenerative approach, the
      term tissue engineering is being increasingly used since it reflects the search
      for interdisciplinary and integrated treatment strategies. However, the drawback
      of this new approach is its intrinsic complexity, which is the result of the
      variety of scientific disciplines involved. This chapter presents a synthetic
      overview of the state of the art in peripheral nerve tissue engineering with a
      look forward at the most promising innovations emerging from basic science
      investigation. This review is intended to set the stage for the collection of
      papers in the thematic issue of the International Review of Neurobiology that is
      focused on the various interdisciplinary approaches in peripheral nerve tissue
      engineering. 

PMID- 24083431
TI  - Bone marrow mesenchymal stem cell transplantation for improving nerve
      regeneration.
AB  - Although the peripheral nervous system has an inherent capacity for regeneration,
      injuries to nerves still result in considerable disabilities. The persistence of
      these disabilities along with the underlying problem of nerve reconstruction has
      motivated neuroscientists worldwide to seek additional therapeutic strategies. In
      recent years, cell-based therapy has emerged as a promising therapeutic tool.
      Schwann cells (SCs) are the main supportive cells for peripheral nerve
      regeneration; however, there are several technical limitations regarding its
      application for cell-based therapy. In this context, bone marrow mesenchymal stem
      cells (BM-MSCs) have been used as alternatives to SCs for treating peripheral
      neuropathies, showing great promise. Several studies have been trying to shed
      light on the mechanisms behind the nerve regeneration-promotion potential of BM
      MSCs. Although not completely clarified, understanding how BM-MSCs exert tissue
      repair effects will facilitate their development as therapeutic agents before
      they become a clinically viable tool for encouraging peripheral nerve
      regeneration. 

PMID- 24083432
TI  - Perspectives of employing mesenchymal stem cells from the Wharton's jelly of the
      umbilical cord for peripheral nerve repair.
AB  - Mesenchymal stem cells (MSCs) from Wharton's jelly present high plasticity and
      low immunogenicity, turning them into a desirable form of cell therapy for the
      injured nervous system. Their isolation, expansion, and characterization have
      been performed from cryopreserved umbilical cord tissue. Great concern has been
      dedicated to the collection, preservation, and transport protocols of the
      umbilical cord after the parturition to the laboratory in order to obtain samples
      with higher number of viable MSCs without microbiological contamination.
      Different biomaterials like chitosan-silicate hybrid, collagen, PLGA90:10,
      poly(DL-lactide-E-caprolactone), and poly(vinyl alcohol) loaded with electrical
      conductive materials, associated to MSCs have also been tested in the rat sciatic
      nerve in axonotmesis and neurotmesis lesions. The in vitro studies of the
      scaffolds included citocompatibility evaluation of the biomaterials used and cell
      characterization by imunocytochemistry, karyotype analysis, differentiation
      capacity into neuroglial-like cells, and flow cytometry. The regeneration process
      follow-up has been performed by functional analysis and the repaired nerves
      processed for stereological studies permitted the morphologic regeneration
      evaluation. The MSCs from Wharton's jelly delivered through tested biomaterials
      should be regarded a potentially valuable tool to improve clinical outcome
      especially after trauma to sensory nerves. In addition, these cells represent a
      noncontroversial source of primitive mesenchymal progenitor cells, which can be
      harvested after birth, cryogenically stored, thawed, and expanded for therapeutic
      uses. The importance of a longitudinal study concerning tissue engineering of the
      peripheral nerve, which includes a multidisciplinary team able to develop
      biomaterials associated to cell therapies, to perform preclinical trials
      concerning animal welfare and the appropriate animal model is here enhanced.

PMID- 24083433
TI  - Adipose-derived stem cells and nerve regeneration: promises and pitfalls.
AB  - In order to improve the outcome of nerve regeneration following peripheral trauma
      injuries, the development of bioengineered nerve grafts has attracted great
      attention in the field of tissue engineering. Adult stem cells constitute the
      ideal alternative to Schwann cells (SCs) as transplantable cells in bioartificial
      nerve grafts. Among the various sources of stem cells with potential applications
      for regenerative medicine, the adipose tissue has been proven to be one of the
      most promising. Adipose-derived stem cells (ASCs) are easily obtained, rapidly
      expanded, show low immunogenicity, and can be differentiated into SCs in vitro.
      This chapter will focus on recent advances in the use of differentiated and
      undifferentiated ASCs for peripheral nerve regeneration, with a critical
      attention for the clinical exploitability of ASC in nerve repair strategies. 

PMID- 24083434
TI  - The pros and cons of growth factors and cytokines in peripheral axon
      regeneration.
AB  - Injury to a peripheral nerve induces a complex cellular and molecular response
      required for successful axon regeneration. Proliferating Schwann cells organize
      into chains of cells bridging the lesion site, which is invaded by macrophages.
      Approximately half of the injured neuron population sends out axons that enter
      the glial guidance channels in response to secreted neurotrophic factors and
      neuropoietic cytokines. These lesion-associated polypeptides create an
      environment that is highly supportive for axon regrowth, particularly after acute
      injury, and ensure that the vast majority of regenerating axons are directed
      toward the distal nerve stump. Unfortunately, most neurotrophic factors and
      neuropoietic cytokines are also strong stimulators of axonal sprouting. Although
      some of the axonal branches will withdraw at later stages, the sprouting effect
      contributes to the misdirection of reinnervation that results in the lack of
      functional recovery observed in many patients with peripheral nerve injuries.
      Here, we critically review the role of neuronal growth factors and cytokines
      during axon regeneration in the peripheral nervous system. Their differential
      effects on axon elongation and sprouting were elucidated in various studies on
      intraneuronal signaling mechanisms following nerve lesion. The present data
      define a goal for future therapeutic strategies, namely, to selectively stimulate
      a Ras/Raf/ERK-mediated axon elongation program over an intrinsic PI3K-dependent
      axonal sprouting program in lesioned motor and sensory neurons. Instead of
      modulating growth factor or cytokine levels at the lesion site, targeting
      specific intraneuronal molecules, such as the negative feedback inhibitors of ERK
      signaling, has been shown to promote long-distance regeneration while avoiding
      sprouting of regenerating axons until they have reached their target areas. 

PMID- 24083435
TI  - Role of inflammation and cytokines in peripheral nerve regeneration.
AB  - This chapter provides a review of immune reactions involved in classic as well as
      alternative methods of peripheral nerve regeneration, and mainly with a view to
      understanding their beneficial effects. Axonal degeneration distal to nerve
      damage triggers a cascade of inflammatory events alongside injured nerve fibers
      known as Wallerian degeneration (WD). The early inflammatory reactions of WD
      comprise the complement system, arachidonic acid metabolites, and inflammatory
      mediators that are related to myelin fragmentation and activation of Schwann
      cells. Fine-tuned upregulation of the cytokine/chemokine network by Schwann cells
      activates resident and hematogenous macrophages to complete the clearance of
      axonal and myelin debris and stimulate regrowth of axonal sprouts. In addition to
      local effects, immune reactions of neuronal bodies and glial cells are also
      implicated in the survival and conditioning of neurons to regenerate severed
      nerves. Understanding of the cellular and molecular interactions between the
      immune system and peripheral nerve injury opens new possibilities for targeting
      inflammatory mediators to improve functional reinnervation. 

PMID- 24083436
TI  - Ghrelin: a novel neuromuscular recovery promoting factor?
AB  - Promoting neuromuscular recovery after neural injury is a major clinical issue.
      While techniques for nerve reconstruction are continuously improving and most
      peripheral nerve lesions can be repaired today, recovery of the lost function is
      usually unsatisfactory. This evidence claims for innovative nonsurgical
      therapeutic strategies that can implement the outcome after neural repair.
      Although no pharmacological approach for improving posttraumatic neuromuscular
      recovery has still entered clinical practice, various molecules are explored in
      experimental models of neural repair. One of such molecules is the circulating
      peptide hormone ghrelin. This hormone has proved to have a positive effect on
      neural repair after central nervous system lesion, and very recently its
      effectiveness has also been demonstrated in preventing posttraumatic skeletal
      muscle atrophy. By contrast, no information is still available about its
      effectiveness on peripheral nerve regeneration although preliminary data from our
      laboratory suggest that this molecule can have an effect also in promoting axonal
      regeneration after nerve injury and repair. Should this be confirmed, ghrelin
      might represent an ideal candidate as a therapeutic agent for improving
      posttraumatic neuromuscular recovery because of its putative effects at all the
      various structural levels involved in this regeneration process, namely, the
      central nervous system, the peripheral nerve, and the target skeletal muscle. 

PMID- 24083437
TI  - Neuregulin 1 role in Schwann cell regulation and potential applications to
      promote peripheral nerve regeneration.
AB  - Neuregulin 1 (NRG1) is a multifunctional and versatile protein: its numerous
      isoforms can signal in a paracrine, autocrine, or juxtacrine manner, playing a
      fundamental role during the development of the peripheral nervous system and
      during the process of nerve repair, suggesting that the treatment with NRG1 could
      improve functional outcome following injury. Accordingly, the use of NRG1 in vivo
      has already yielded encouraging results. The aim of this review is to focus on
      the role played by the different NRG1 isoforms during peripheral nerve
      regeneration and remyelination and to identify good candidates to be used for the
      development of tissue engineered medical devices delivering NRG1, with the
      objective of promoting better nerve repair. 

PMID- 24083438
TI  - Extracellular matrix components in peripheral nerve regeneration.
AB  - Injured axons of the peripheral nerve are able to regenerate and, eventually,
      reinnervate target organs. However, functional recovery is usually poor after
      severe nerve injuries. The switch of Schwann cells to a proliferative state,
      secretion of trophic factors, and the presence of extracellular matrix (ECM)
      molecules (such as collagen, laminin, or fibronectin) in the distal stump are key
      elements to create a permissive environment for axons to grow. In this review, we
      focus attention on the ECM components and their tropic role in axonal
      regeneration. These components can also be used as molecular cues to guide the
      axons through artificial nerve guides in attempts to better mimic the natural
      environment found in a degenerating nerve. Most used scaffolds tested are based
      on natural molecules that form the ECM, but use of synthetic polymers and
      functionalization of hydrogels are bringing new options. Progress in tissue
      engineering will eventually lead to the design of composite artificial nerve
      grafts that may replace the use of autologous nerve grafts to sustain
      regeneration over long gaps. 

PMID- 24083439
TI  - Preface. tissue engineering of the peripheral nerve: stem cells and regeneration
      promoting factors.

PMID- 24083441
TI  - S1 and S2 states of linear and zigzag cata-condensed hydrocarbons.
AB  - We investigated the S1 and S2 states of linear and zigzag cata-condensed
      hydrocarbons on the basis of the results of jet spectroscopy and theoretical
      calculations. The S1 states of anthracene and tetracene are represented by the
      HOMO -> LUMO configuration (Phi(A)), whereas those of phenanthrene and chrysene
      are represented by HOMO-1 -> LUMO and HOMO -> LUMO+1 configurations (Phi(B)). We
      found that the fluorescence lifetime varied with different vibronic levels in the
      S1 states of linear cata-condensed hydrocarbons due to the mode-selective
      internal conversion to the S0 state. This selectivity is likely to be seen in the
      S1 Phi(A) state of the D(2h) molecule.

PMID- 24083440
TI  - Investigating silent strokes in hypertensives: a magnetic resonance imaging study
      (ISSYS): rationale and protocol design.
AB  - BACKGROUND: Silent brain infarcts are detected by neuroimaging in up to 20% of
      asymptomatic patients based on population studies. They are five times more
      frequent than stroke in general population, and increase significantly both with
      advancing age and hypertension. Moreover, they are independently associated with
      the risk of future stroke and cognitive decline.Despite these numbers and the
      clinical consequences of silent brain infarcts, their prevalence in Mediterranean
      populations is not well known and their role as predictors of future
      cerebrovascular and cardiovascular events in hypertensive remains to be
      determined.ISSYS (Investigating Silent Strokes in Hypertensives: a magnetic
      resonance imaging study) is an observational cross-sectional and longitudinal
      study aimed to: 1- determine the prevalence of silent cerebrovascular infarcts in
      a large cohort of 1000 hypertensives and to study their associated factors and 2
      to study their relationship with the risk of future stroke and cognitive decline.
      METHODS/DESIGN: Cohort study in a randomly selected sample of 1000 participants,
      hypertensive aged 50 to 70 years old, with no history of previous stroke or
      dementia.On baseline all participants will undergo a brain MRI to determine the
      presence of brain infarcts and other cerebrovascular lesions (brain microbleeds,
      white matter changes and enlarged perivascular spaces) and will be also tested to
      determine other than brain organ damage (heart-left ventricular hypertrophy,
      kidney-urine albumin to creatinine ratio, vessels-pulse wave velocity, ankle
      brachial index), in order to establish the contribution of other subclinical
      conditions to the risk of further vascular events. Several sub-studies assessing
      the role of 24 hour ambulatory BP monitoring and plasma or genetic biomarkers
      will be performed.Follow-up will last for at least 3 years, to assess the rate of
      further stroke/transient ischemic attack, other cardiovascular events and
      cognitive decline, and their predictors. DISCUSSION: Improving the knowledge on
      the frequency and determinants of these lesions in our setting might help in the
      future to optimize treatments or establish new preventive strategies to minimize
      clinical and socioeconomic consequences of stroke and cognitive decline.

PMID- 24083444
TI  - Slow DNA transport through nanopores in hafnium oxide membranes.
AB  - We present a study of double- and single-stranded DNA transport through nanopores
      fabricated in ultrathin (2-7 nm thick) freestanding hafnium oxide (HfO2)
      membranes. The high chemical stability of ultrathin HfO2 enables long-lived
      experiments with <2 nm diameter pores that last several hours, in which we
      observe >50 000 DNA translocations with no detectable pore expansion. Mean DNA
      velocities are slower than velocities through comparable silicon nitride pores,
      providing evidence that HfO2 nanopores have favorable physicochemical
      interactions with nucleic acids that can be leveraged to slow down DNA in a
      nanopore.

PMID- 24083445
TI  - Antioxidant potential, cytotoxic activity and total phenolic content of Alpinia
      pahangensis rhizomes.
AB  - BACKGROUND: Alpinia pahangensis, a wild ginger distributed in the lowlands of
      Pahang, Malaysia, is used by the locals to treat flatulence. In this study, the
      antioxidant and cytotoxic activities of the crude aqueous methanol and
      fractionated extracts of Alpinia pahangensis against five different cancer and
      one normal cell lines were investigated. The total phenolic content of each
      extract and its fractions were also quantified. This is the first report on the
      antioxidant and cytotoxic activities of Alpinia pahangensis extract. METHODS: In
      the current study, the crude methanol and fractionated extract of the rhizomes of
      Alpinia pahangensis were investigated for their antioxidant activity using four
      different assays namely, the DPPH scavenging activity, superoxide anion
      scavenging, beta-carotene bleaching and reducing power assays whilst their
      phenolic contents were measured by the Folin-Ciocalteu's method.In vitro neutral
      red cytotoxicity assay was employed to evaluate the cytotoxic activity against
      five different cancer cell lines, colon cancer (HCT 116 and HT-29), cervical
      cancer (Ca Ski), breast cancer (MCF7) and lung cancer (A549) cell lines, and one
      normal cell line (MRC-5). The extract that showed high cytotoxic activity was
      further investigated for its chemical constituents by GC-MS (gas chromatography
      mass spectrometry) analysis. RESULTS: The ethyl acetate fraction showed the
      strongest DPPH radical scavenging (0.35 +/- 0.094 mg/ml) and SOD activities
      (51.77 +/- 4.9%) whilst the methanol extract showed the highest reducing power
      and also the strongest antioxidant activity in the beta-carotene bleaching assays
      in comparison to other fractions. The highest phenolic content was found in the
      ethyl acetate fraction, followed by the crude methanol extract, hexane and water
      fractions. The results showed a positive correlation between total phenolic
      content with DPPH radical scavenging capacities and SOD activities. The hexane
      fraction showed potent cytotoxic effect against KB, Ca Ski and HCT 116 cell lines
      with IC50 of 5.8 +/- 0.1 and 9.1 +/- 2.0 ug/ml, respectively. The major
      components of hexane fraction analysed by GC-MS analysis were mostly methyl
      esters. CONCLUSIONS: The current study suggests that the methanol extract and
      ethyl acetate fraction of A. pahangensis is a potential source of natural
      antioxidant for protective as well as prevention of life-threatening diseases.
      The hexane fraction of A. pahangensis may have the potential to be developed into
      therapeutic option for treating cancer.

PMID- 24083446
TI  - Late-onset Sheehan's syndrome presenting with rhabdomyolysis and hyponatremia: a
      case report.
AB  - INTRODUCTION: Hyponatremia associated with rhabdomyolysis is a rare event and a
      correct diagnostic approach is required to rule out this or other diseases as a
      primary cause and to avoid other complications resulting from a lack of
      appropriate treatment. CASE PRESENTATION: A 64-year-old Caucasian woman presented
      to our facility with worsening fatigue, slurred speech, nausea and vomiting, and
      high serum levels of creatine kinase and myoglobin together with hyponatremia.
      Normal arterial blood gas analysis results, normal serum potassium levels,
      increased urine sodium levels, urine specific gravity of >1003N/m3 and low urine
      volume suggested an endocrine etiology. Her low cortisol and thyroid hormone
      serum levels suggested a pituitary disorder. A magnetic resonance imaging study
      showed atrophy of her pituitary gland. A more detailed study of our patient's
      obstetric history revealed a post-partum hemorrhage 30 years earlier. She was
      diagnosed as having late-onset Sheehan's syndrome and treated with hormone
      replacement therapy, which normalized her clinical picture. CONCLUSIONS: This
      case report shows that, in hyponatremia-associated rhabdomyolysis, an
      endocrinological origin should always be considered. This should include
      Sheehan's syndrome as it can occur with late onset.

PMID- 24083447
TI  - Effect of pH and oxygen atom of the hydrophobic chain on the self-assembly
      property and morphology of the pyridyl boronic acid based amphiphiles.
AB  - The surface activity and aggregation behavior of two synthesized boronic acid
      based anionic surfactants, sodium salt of 2-dodecyl pyridine-5-boronic acid
      (SDDPB) and sodium salt of 2-oxydodecyl pyridine-5-boronic acid (SODDPB), were
      studied in buffer solution at pH 9 and 13 containing carbohydrates. The self
      assembly formation was investigated by use of a number of techniques including
      surface tension, conductivity, fluorescence spectroscopy, dynamic light
      scattering, X-ray diffraction, and transmission electron microscopy (TEM). Both
      of the amphiphiles exhibit a single break in the surface tension vs
      log(concentration) plots, indicating existence of one critical aggregation
      concentration. Steady state fluorescence spectroscopy was used to determine the
      polarity indexes using pyrene and the rigidity of the microenvironments of the
      aggregates using 1,6-diphenyl-1,3,5-hexatriene (DPH) as fluorescence probe
      molecules. The pKa's of both amphiphiles were determined in buffer solutions of
      different pH's. XRD studies were performed to shed light on the morphology of the
      self-assemblies. TEM micrographs revealed the existence of vesicles for both the
      amphiphiles in buffer solution of pH 9, but at pH 13, TEM pictures indicate the
      existence of closed vesicles in SDDPB solution and at concentrated solution the
      vesicles are fused to form sponge-like micelles. After aging the vesicular
      solution of pH 13 of SDDPB, the closed vesicles are destroyed. In contrast, for
      SODDPB at pH 13, TEM pictures suggest the existence of spherical and complex
      micelles in solution which were further transformed into crystal-like structure
      upon aging. The average hydrodynamic radii were determined by dynamic light
      scattering measurement. Therefore, for the first time, we have successfully
      synthesized two new surfactants containing pyridyl-boronic acid as a headgroup
      which shows remarkable tuning of morphology in two different pH's and in the
      presence of two different carbohydrates. 

PMID- 24083448
TI  - Reduction-cleavable polymeric vesicles with efficient glutathione-mediated drug
      release behavior for reversing drug resistance.
AB  - In the treatment of cancer, multidrug resistance (MDR) has been the major
      obstacle to the success of chemotherapy. The underlying mechanism relies on the
      overexpression of drug-efflux transporters that prevent the intracellular
      transport of the drug. In this study, reduction-cleavable vesicles were designed
      and developed with efficient glutathione-mediated drug-release behavior for
      reversing drug resistance. Polymeric vesicles were self-assembled from triblock
      copolymers with disulfide-bond-linked poly(ethylene glycol) (PEG) and
      poly(epsilon-benzyloxycarbonyl-L-lysine) (PzLL). Observations from transmission
      electron microscopy (TEM) and confocal laser scanning microscopy (CLSM) outline
      an obvious hollow structure surrounded by a thin outer layer, indicating the
      successful formation of the vesicles. Using fluorescently detectable doxorubicin
      hydrochloride (DOX.HCl) as the model drug, a significant acceleration of drug
      release regulated by glutathione (GSH) was found (>3-fold difference). Upon
      incubation of the DOX.HCl-loaded polymeric vesicles with the HeLa cervical cancer
      cell line exposed to glutathione, an enhanced nuclear accumulation of DOX.HCl was
      observed, elicited by the preferred disassembly of the vesicle structure under
      reducing conditions. Importantly, by using the gemcitabine hydrochloride (GC.HCl)
      resistant breast cancer cell line MDA-MB-231, it was found that cell viability
      was significantly reduced after treatment with GC.HCl-loaded polymeric vesicles,
      indicating that these vesicles can help to reverse the drug resistance.

PMID- 24083449
TI  - The Bcl-2/Bax and Ras/Raf/MEK/ERK signaling pathways: implications in pediatric
      leukemia pathogenesis and new prospects for therapeutic approaches.
AB  - The Bcl-2/Bcl-xL/Bax and the Ras/Raf/MEK/ERK (MAPK) pathways are often
      deregulated in many human cancers and especially in acute lymphoblastic leukemia
      and acute myeloid leukemia. A result of molecular alterations of these pathways
      is uncontrolled cell growth and survival, ultimately resulting in oncogenic
      transformation and progression. Aberrant expression of Bcl-2/Bax and MAPK can
      lead to therapeutic resistance. In this review, the Bcl-2 and MAPK pathways are
      analyzed, focusing the attention on their molecular alterations, and the complex
      interactions between these signaling cascades are also analyzed. The observation
      that both MAPK and Bcl-2/Bax signaling play a central role in the pathogenesis of
      human cancer suggests that this kinase cascade represents a novel opportunity for
      the development of new anticancer targeted therapies designed to be less toxic
      than conventional chemotherapy. The evidence that they are often implicated in
      sensitivity and resistance to leukemia therapy suggests that characterization of
      the cancer genome may offer personalized cancer genomic information that can lead
      to the formulation of much more effective personalized therapy. 

PMID- 24083450
TI  - Localization of organic anion transporting polypeptide (Oatp) 1a4 and Oatp1c1 at
      the rat blood-retinal barrier.
AB  - BACKGROUND: Organic anion transporting polypeptide (Oatp) transporters at the
      blood-brain barrier (BBB) and the blood-retinal barrier (BRB), which consists of
      retinal capillary endothelial cells and retinal pigment epithelial cells, are
      major determinants of the control of anionic drugs into the brain and retina.
      Although Oatp1a4 (Slco1a4) and Oatp1c1 (Slco1c1) are known to be expressed in the
      abluminal and luminal membrane of the rat BBB and Oatp1a4 is known to be
      expressed at the BRB, the expression and localization of Oatp1c1 at the BRB and
      subcellular localization of Oatp1a4 at the BRB have received little attention.
      Therefore, the purpose of present study was to determine the cellular and
      subcellular localization of Oatp1a4 and 1c1 at the BRB. METHODS: We used guinea
      pig polyclonal antibodies to Oatp1a4 and 1c1 for immunoblot and
      immunohistochemical analysis to determine their cellular and subcellular
      distributions in the rat retina. We compared these distributions with those of
      the glucose transporter 1 (GLUT1/Slc2a1). Whole brain, brain capillary fractions
      and kidney were used as control. RESULTS: Oatp1a4 and 1c1 immunoreactivities were
      detected in the rat retinal capillaries and co-localized with GLUT1, suggesting
      that both proteins are located on the abluminal and luminal membrane of the
      retinal capillary endothelial cells. Oatp1a4 and 1c1 immunoreactivities were
      preferentially detected on the apical and basolateral membrane of rat retinal
      pigment epithelial cells, respectively, suggesting that Oatp1a4 and 1c1 are
      localized on the apical membrane and the basolateral membrane of the retinal
      pigment epithelial cells, respectively. CONCLUSION: Oatp1a4 and 1c1 are present
      at the BRB and contribute to the transcellular transport of amphipathic organic
      anions across the BRB.

PMID- 24083451
TI  - Signal transduction pathways in Synechocystis sp. PCC 6803 and biotechnological
      implications under abiotic stress.
AB  - Cyanobacteria have developed various response mechanisms in long evolution to
      sense and adapt to external or internal changes under abiotic stresses. The
      signal transduction system of a model cyanobacterium Synechocystis sp. PCC 6803
      includes mainly two-component signal transduction systems of eukaryotic-type
      serine/threonine kinases (STKs), on which most have been investigated at present.
      These two-component systems play a major role in regulating cell activities in
      cyanobacteria. More and more co-regulation and crosstalk regulations among signal
      transduction systems had been discovered due to increasing experimental data, and
      they are of great importance in corresponding to abiotic stresses. However,
      mechanisms of their functions remain unknown. Nevertheless, the two signal
      transduction systems function as an integral network for adaption in different
      abiotic stresses. This review summarizes available knowledge on the signal
      transduction network in Synechocystis sp. PCC 6803 and biotechnological
      implications under various stresses, with focuses on the co-regulation and
      crosstalk regulations among various stress-responding signal transduction
      systems. 

PMID- 24083453
TI  - Are white-rot fungi a real biotechnological option for the improvement of
      environmental health?
AB  - The use of white-rot fungi as a biotechnological tool for cleaning the
      environment of recalcitrant pollutants has been under evaluation for several
      years. However, it is still not possible to find sufficiently detailed
      investigations of this subject to conclude that these fungi can decontaminate the
      environment. In the present review, we have summarized and discussed evidence
      about the potential of white-rot fungi to degrade such pollutants as polycyclic
      aromatic hydrocarbons, dyes or antibiotics as an example of the complex
      structures that these microorganisms can attack. This review also discusses field
      experiment results and limitations of white-rot fungi trials from contaminated
      sites. Moreover, the use of catabolic potential of white-rot fungi in
      biopurification systems (biobeds) is also discussed. The current status and
      future perspectives of white-rot fungi, as a viable biotechnological alternative
      for improvement of environmental health are noted. 

PMID- 24083454
TI  - Recent trends in biological extraction of chitin from marine shell wastes: a
      review.
AB  - The natural biopolymer chitin and its deacetylated product chitosan are widely
      used in innumerable applications ranging from biomedicine, pharmaceuticals, food,
      agriculture and personal care products to environmental sector. The abundant and
      renewable marine processing wastes are commercially exploited for the extraction
      of chitin. However, the traditional chitin extraction processes employ harsh
      chemicals at elevated temperatures for a prolonged time which can harm its
      physico-chemical properties and are also held responsible for the deterioration
      of environmental health. In view of this, green extraction methods are
      increasingly gaining popularity due to their environmentally friendly nature. The
      bioextraction of chitin from crustacean shell wastes has been increasingly
      researched at the laboratory scale. However, the bioextraction of chitin is not
      currently exploited to its maximum potential on the commercial level.
      Bioextraction of chitin is emerging as a green, cleaner, eco-friendly and
      economical process. Specifically in the chitin extraction, microorganisms
      mediated fermentation processes are highly desirable due to easy handling,
      simplicity, rapidity, controllability through optimization of process parameters,
      ambient temperature and negligible solvent consumption, thus reducing
      environmental impact and costs. Although, chitin production from crustacean shell
      waste through biological means is still at its early stage of development, it is
      undergoing rapid progress in recent years and showing a promising prospect.
      Driven by reduced energy, wastewater or solvent, advances in biological
      extraction of chitin along with valuable by-products will have high economic and
      environmental impact.

PMID- 24083452
TI  - Clinical translation of stem cells: insight for cartilage therapies.
AB  - The limited regenerative capacity of articular cartilage and deficiencies of
      current treatments have motivated the investigation of new repair technologies.
      In vitro cartilage generation using primary cell sources is limited by cell
      availability and expansion potential. Pluripotent stem cells possess the capacity
      for chondrocytic differentiation and extended expansion, providing a potential
      future solution to cell-based cartilage regeneration. However, despite successes
      in producing cartilage using adult and embryonic stem cells, the translation of
      these technologies to the clinic has been severely limited. This review discusses
      recent advances in stem cell-based cartilage tissue engineering and the major
      current limitations to clinical translation of these products. Concerns regarding
      appropriate animal models and studies, stem cell manufacturing, and relevant
      regulatory processes and guidelines will be addressed. Understanding the
      significant hurdles limiting the clinical use of stem cell-based cartilage may
      guide future developments in the fields of tissue engineering and regenerative
      medicine.

PMID- 24083455
TI  - Targeting ribonucleotide reductase for cancer therapy.
AB  - INTRODUCTION: Ribonucleotide reductase (RR) is a unique enzyme, because it is
      responsible for reducing ribonucleotides to their corresponding
      deoxyribonucleotides, which are the building blocks required for DNA replication
      and repair. Dysregulated RR activity is associated with genomic instability,
      malignant transformation and cancer development. The use of RR inhibitors, either
      as a single agent or combined with other therapies, has proven to be a promising
      approach for treating solid tumors and hematological malignancies. AREAS COVERED:
      This review covers recent publications in the area of RR, which include: i) the
      structure, function and regulation of RR; ii) the roles of RR in cancer
      development; iii) the classification, mechanisms and clinical application of RR
      inhibitors for cancer therapy and iv) strategies for developing novel RR
      inhibitors in the future. EXPERT OPINION: Exploring the possible nonenzymatic
      roles of RR subunit proteins in carcinogenesis may lead to new rationales for
      developing novel anticancer drugs. Updated information about the structure and
      holoenzyme models of RR will help in identifying potential sites in the protein
      that could be targets for novel RR inhibitors. Determining RR activity and
      subunit levels in clinical samples will provide a rational platform for
      developing personalized cancer therapies that use RR inhibitors.

PMID- 24083456
TI  - Nacre-mimetic clay/xyloglucan bionanocomposites: a chemical modification route
      for hygromechanical performance at high humidity.
AB  - Nacre-mimetic bionanocomposites of high montmorillonite (MTM) clay content,
      prepared from hydrocolloidal suspensions, suffer from reduced strength and
      stiffness at high relative humidity. We address this problem by chemical
      modification of xyloglucan in (XG)/MTM nacre-mimetic nanocomposites, by
      subjecting the XG to regioselective periodate oxidation of side chains to enable
      it to form covalent cross-links to hydroxyl groups in neighboring XG chains or to
      the MTM surface. The resulting materials are analyzed by FTIR spectroscopy,
      thermogravimetric analysis, carbohydrate analysis, calorimetry, X-ray
      diffraction, scanning electron microscopy, tensile tests, and oxygen barrier
      properties. We compare the resulting mechanical properties at low and high
      relative humidity. The periodate oxidation leads to a strong increase in modulus
      and strength of the materials. A modulus of 30 GPa for cross-linked composite at
      50% relative humidity compared with 13.7 GPa for neat XG/MTM demonstrates that
      periodate oxidation of the XG side chains leads to crucially improved stress
      transfer at the XG/MTM interface, possibly through covalent bond formation. This
      enhanced interfacial adhesion and internal cross-linking of the matrix moreover
      preserves the mechanical properties at high humidity condition and leads to a
      Young's modulus of 21 GPa at 90%RH. 

PMID- 24083457
TI  - Cerebellar motor learning deficits in medicated and medication-free men with
      recent-onset schizophrenia.
AB  - BACKGROUND: The notion that cerebellar deficits may underlie clinical symptoms in
      people with schizophrenia is tested by evaluating 2 forms of cerebellar learning
      in patients with recent-onset schizophrenia. A potential medication effect is
      evaluated by including patients with or without antipsychotics. METHODS: We
      assessed saccadic eye movement adaptation and eyeblink conditioning in men with
      recent-onset schizophrenia who were taking antipsychotic medication or who were
      antipsychotic-free and in age-matched controls. RESULTS: We included 39 men with
      schizophrenia (10 who were taking clozapine, 16 who were taking haloperidol and
      13 who were antipsychotic-free) and 29 controls in our study. All participants
      showed significant saccadic adaptation. Adaptation strength did not differ
      between healthy controls and men with schizophrenia. The speed of saccade
      adaptation, however, was significantly lower in men with schizophrenia. They
      showed a significantly lower increase in the number of conditioned eyeblink
      responses. Over all experiments, no consistent effects of medication were
      observed. These outcomes did not correlate with age, years of education,
      psychopathology or dose of antipsychotics. LIMITATIONS: As patients were not
      randomized for treatment, an influence of confounding variables associated with
      medication status cannot be excluded. Individual patients also varied along the
      schizophrenia spectrum despite the relative homogeneity with respect to onset of
      illness and short usage of medication. Finally, the relatively small number of
      participants may have concealed effects as a result of insufficient statistical
      power. CONCLUSION: We found several cerebellar learning deficits in men with
      schizophrenia that we cannot attribute to the use of antipsychotics. Although
      this finding, combined with the fact that deficits are already present in
      patients with recent-onset schizophrenia, could suggest that cerebellar
      impairments are a trait deficit in people with schizophrenia. This should be
      confirmed in longitudinal studies.

PMID- 24083458
TI  - Abnormal synchrony of resting state networks in premanifest and symptomatic
      Huntington disease: the IMAGE-HD study.
AB  - BACKGROUND: Functional neural impairments have been documented in people with
      symptomatic Huntington disease (symp-HD) and in premanifest gene carriers (pre
      HD). This study aimed to characterize synchrony in resting state cerebral
      networks in both pre-HD and symp-HD populations and to determine its association
      with disease burden and neurocognitive functions. METHODS: We acquired functional
      magnetic resonance imaging (fMRI) data from pre-HD, symp-HD and healthy control
      participants. The fMRI data were analyzed using multisubject independent
      component analysis and dual regression. We compared networks of interest among
      the groups using a nonparametric permutation method and correcting for multiple
      comparisons. RESULTS: Our study included 25 people in the pre-HD, 23 in the symp
      HD and 18 in the healthy control groups. Compared with the control group, the pre
      HD group showed decreased synchrony in the sensorimotor and dorsal attention
      networks; decreased level of synchrony in the sensorimotor network was associated
      with poorer motor performance. Compared with the control group, the symp-HD group
      showed widespread reduction in synchrony in the dorsal attention network, which
      was associated with poorer cognitive performance. The posterior putamen and
      superior parietal cortex were functionally disconnected from the frontal
      executive network in the symp-HD compared with control and pre-HD groups.
      Furthermore, the left frontoparietal network showed areas of increased synchrony
      in the symp-HD compared with the pre-HD group. LIMITATIONS: We could not directly
      correct for influence of autonomic changes (e.g., heart rate) and respiration on
      resting state synchronization. CONCLUSION: Our findings suggest that aberrant
      synchrony in the sensorimotor and dorsal attention networks may serve as an early
      signature of neural change in pre-HD individuals. The altered synchrony in dorsal
      attention, frontoparietal and corticostriatal networks may contribute to the
      development of clinical symptoms in people with Huntington disease.

PMID- 24083460
TI  - Arterial input function in perfusion MRI: a comprehensive review.
AB  - Cerebral perfusion, also referred to as cerebral blood flow (CBF), is one of the
      most important parameters related to brain physiology and function. The technique
      of dynamic-susceptibility contrast (DSC) MRI is currently the most commonly used
      MRI method to measure perfusion. It relies on the intravenous injection of a
      contrast agent and the rapid measurement of the transient signal changes during
      the passage of the bolus through the brain. Central to quantification of CBF
      using this technique is the so-called arterial input function (AIF), which
      describes the contrast agent input to the tissue of interest. Due to its
      fundamental role, there has been a lot of progress in recent years regarding how
      and where to measure the AIF, how it influences DSC-MRI quantification, what
      artefacts one should avoid, and the design of automatic methods to measure the
      AIF. The AIF is also directly linked to most of the major sources of artefacts in
      CBF quantification, including partial volume effect, bolus delay and dispersion,
      peak truncation effects, contrast agent non-linearity, etc. While there have been
      a number of good review articles on DSC-MRI over the years, these are often
      comprehensive but, by necessity, with limited in-depth discussion of the various
      topics covered. This review article covers in greater depth the issues associated
      with the AIF and their implications for perfusion quantification using DSC-MRI. 

PMID- 24083459
TI  - Characterization of major depressive disorder using a multiparametric
      classification approach based on high resolution structural images.
AB  - BACKGROUND: Major depressive disorder (MDD) is one of the most disabling mental
      illnesses. Previous neuroanatomical studies of MDD have revealed regional
      alterations in grey matter volume and density. However, owing to the
      heterogeneous symptomatology and complex etiology, MDD is likely to be associated
      with multiple morphometric alterations in brain structure. We sought to
      distinguish first-episode, medication-naive, adult patients with MDD from healthy
      controls and characterize neuroanatomical differences between the groups using a
      multiparameter classification approach. METHODS: We recruited medication-naive
      patients with first-episode depression and healthy controls matched for age, sex,
      handedness and years of education. High-resolution T1-weighted images were used
      to extract 7 morphometric parameters, including both volumetric and geometric
      features, based on the surface data of the entire cerebral cortex. These
      parameters were used to compare patients and controls using multivariate support
      vector machine, and the regions that informed the discrimination between the 2
      groups were identified based on maximal classification weights. RESULTS: Thirty
      two patients and 32 controls participated in the study. Both volumetric and
      geometric parameters could discriminate patients with MDD from healthy controls,
      with cortical thickness in the right hemisphere providing the greatest accuracy
      (78%, p <= 0.001). This discrimination was informed by a bilateral network
      comprising mainly frontal, temporal and parietal regions. LIMITATIONS: The sample
      size was relatively small and our results were based on first-episode, medication
      naive patients. CONCLUSION: Our investigation demonstrates that multiple cortical
      features are affected in medication-naive patients with first-episode MDD. These
      findings extend the current understanding of the neuropathological underpinnings
      of MDD and provide preliminary support for the use of neuroanatomical scans in
      the early detection of MDD.

PMID- 24083461
TI  - Quantitative cw Overhauser effect dynamic nuclear polarization for the analysis
      of local water dynamics.
AB  - Liquid state Overhauser effect Dynamic Nuclear Polarization (ODNP) has
      experienced a recent resurgence of interest. The ODNP technique described here
      relies on the double resonance of electron spin resonance (ESR) at the most
      common, i.e. X-band (~10GHz), frequency and 1H nuclear magnetic resonance (NMR)
      at ~15 MHz. It requires only a standard continuous wave (cw) ESR spectrometer
      with an NMR probe inserted or built into an X-band cavity. We focus on reviewing
      a new and powerful manifestation of ODNP as a high frequency NMR relaxometry tool
      that probes dipolar cross relaxation between the electron spins and the 1H
      nuclear spins at X-band frequencies. This technique selectively measures the
      translational mobility of water within a volume extending 0.5-1.5 nm outward from
      a nitroxide radical spin probe that is attached to a targeted site of a
      macromolecule. It allows one to study the dynamics of water that hydrates or
      permeates the surface or interior of proteins, polymers, and lipid membrane
      vesicles. We begin by reviewing the recent advances that have helped develop ODNP
      into a tool for mapping the dynamic landscape of hydration water with sub
      nanometer locality. In order to bind this work coherently together and to place
      it in the context of the extensive body of research in the field of NMR
      relaxometry, we then rephrase the analytical model and extend the description of
      the ODNP-derived NMR signal enhancements. This extended model highlights several
      aspects of ODNP data analysis, including the importance of considering all
      possible effects of microwave sample heating, the need to consider the error
      associated with various relaxation rates, and the unique ability of ODNP to probe
      the electron-1H cross-relaxation process, which is uniquely sensitive to fast
      (tens of ps) dynamical processes. By implementing the relevant corrections in a
      stepwise fashion, this paper draws a consensus result from previous ODNP
      procedures and then shows how such data can be further corrected to yield clear
      and reproducible saturation of the NMR hyperpolarization process. Finally,
      drawing on these results, we broadly survey the previous ODNP dynamics
      literature. We find that the vast number of published, empirical hydration
      dynamics data can be reproducibly classified into regimes of surface,
      interfacial, vs. buried water dynamics.

PMID- 24083463
TI  - Phosphoproteomic dynamics of chickpea (Cicer arietinum L.) reveals shared and
      distinct components of dehydration response.
AB  - Reversible protein phosphorylation is a ubiquitous regulatory mechanism that
      plays critical roles in transducing stress signals to bring about coordinated
      intracellular responses. To gain better understanding of dehydration response in
      plants, we have developed a differential phosphoproteome in a food legume,
      chickpea (Cicer arietinum L.). Three-week-old chickpea seedlings were subjected
      to progressive dehydration by withdrawing water, and the changes in the
      phosphorylation status of a large repertoire of proteins were monitored. The
      proteins were resolved by 2-DE and stained with phosphospecific fluorescent Pro-Q
      Diamond dye. Mass spectrometric analysis led to the identification of 91 putative
      phosphoproteins, presumably involved in a variety of functions including cell
      defense and rescue, photosynthesis and photorespiration, molecular chaperones,
      and ion transport, among others. Multiple sites of phosphorylation were predicted
      on several key elements, which include both the regulatory as well as the
      functional proteins. A critical survey of the phosphorylome revealed a DREPP
      (developmentally regulated plasma membrane protein) plasma membrane polypeptide
      family protein, henceforth designated CaDREPP1. The transcripts of CaDREPP1 were
      found to be differentially regulated under dehydration stress, further
      corroborating the proteomic results. This work provides new insights into the
      possible phosphorylation events triggered by the conditions of progressive water
      deficit in plants. 

PMID- 24083465
TI  - Effects of material morphology on the phototoxicity of nano-TiO2 to bacteria.
AB  - Nanostructured titania (nano-TiO2) is produced in diverse shapes, but it remains
      largely unknown how tuning the morphology of nano-TiO2 may alter its toxicity.
      Herein, we show that material morphology plays a critical role in regulating the
      phototoxicity of nano-TiO2 to bacteria. Low-dimensional nano-TiO2, including
      nanotubes, nanorods, and nanosheets, were synthesized hydrothermally, and their
      effects on the bacterial viability of Escherichia coli and Aeromonas hydrophila
      were compared to spherical nanostructures (anatase nanospheres and P25). Results
      reveal that TiO2 nanotubes and nanosheets are less phototoxic than their rod- and
      sphere-shape counterparts under simulated solar irradiation. None of the tested
      nano-TiO2 shows toxicity in the dark. In contrast to their diminished
      phototoxicity, however, TiO2 nanotubes and nanosheets exhibit comparable or even
      higher photoactivity than other nanostructures. Observations by scanning
      transmission electron microscopy suggest that material morphology influences nano
      TiO2 phototoxicity by governing how nano-TiO2 particles align at the bacterial
      cell surface. Overall, when comparing materials with different morphologies and
      dimensionality, nano-TiO2 phototoxicity is not a simple function of
      photocatalytic reactivity or ROS production. Instead, we propose that the
      evaluation of nano-TiO2 phototoxicity encompasses a three-pronged approach,
      involving the intrinsic photoactivity, aggregation of nano-TiO2, and the nano
      TiO2/bacteria surface interactions. 

PMID- 24083467
TI  - Polymorphism in self-assembled terphenylthiolate monolayers on Au(111).
AB  - Self-assembled monolayers (SAMs) of terphenylthiol (TPT) on gold Au(111)
      substrates exhibit well-ordered structures over large scales if they are annealed
      in ethanol at 40  degrees C after their formation. Using high-resolution STM, two
      distinct, ordered phases could be observed. The simpler phase, designated as
      alpha-phase, consists of closely packed molecules in the well-known (2?3 * ?3)R30
      degrees  structure. It could be demonstrated that under less suitable imaging
      conditions this phase can be mistaken as the hexagonal (?3 * ?3)R30 degrees ,
      which resolves a discrepancy in between previous reports. The second phase is
      characterized by a stripe pattern with a periodicity of 2.0 nm and can be
      described by a point-on-line incommensurate (4 * n) ([Formula: see text]) lattice
      with n close to 8. This beta-phase contains four pairs of terphenylthiolate
      molecules, which might be held together by either disulfide bonds or the recently
      discussed S-Au-S motif, and is thus 35% +/- 15% less densely packed than the
      alpha-phase. The coexistence of these phases explains the variability of
      spectroscopic results obtained in the past for terphenylthiolate layers, since
      their relative proportion determines the average thicknesses/tilt angles found in
      these studies.

PMID- 24083462
TI  - Protein folding on the ribosome studied using NMR spectroscopy.
AB  - NMR spectroscopy is a powerful tool for the investigation of protein folding and
      misfolding, providing a characterization of molecular structure, dynamics and
      exchange processes, across a very wide range of timescales and with near atomic
      resolution. In recent years NMR methods have also been developed to study protein
      folding as it might occur within the cell, in a de novo manner, by observing the
      folding of nascent polypeptides in the process of emerging from the ribosome
      during synthesis. Despite the 2.3 MDa molecular weight of the bacterial 70S
      ribosome, many nascent polypeptides, and some ribosomal proteins, have sufficient
      local flexibility that sharp resonances may be observed in solution-state NMR
      spectra. In providing information on dynamic regions of the structure, NMR
      spectroscopy is therefore highly complementary to alternative methods such as X
      ray crystallography and cryo-electron microscopy, which have successfully
      characterized the rigid core of the ribosome particle. However, the low working
      concentrations and limited sample stability associated with ribosome-nascent
      chain complexes means that such studies still present significant technical
      challenges to the NMR spectroscopist. This review will discuss the progress that
      has been made in this area, surveying all NMR studies that have been published to
      date, and with a particular focus on strategies for improving experimental
      sensitivity.

PMID- 24083466
TI  - Human casein alpha s1 (CSN1S1) skews in vitro differentiation of monocytes
      towards macrophages.
AB  - BACKGROUND: The milk-derived protein human Casein alpha s1 (CSN1S1) has recently
      been detected in blood cells and was shown to possess proinflammatory properties.
      In the present study, we investigated the effect of CSN1S1 on the differentiation
      of monocytes. METHODS: Primary human monocytes were stimulated with recombinant
      CSN1S1 and compared to cells stimulated with GM-CSF/IL-4 or M-CSF/IFNgamma.
      Morphological changes were assessed by microscopy and quantification of surface
      markers of differentiation by FACS analysis. Phagocytic activity of CSN1S1
      stimulated cells was measured by quantification of zymosan labeled particle
      uptake. The role of mitogen activated protein kinases for CSN1S1-induced
      differentiation of monocytes and proinflammatory cytokine expression was assessed
      by supplementation of specific inhibitors. RESULTS: CSN1S1 at a concentration of
      10 MUg/ml resulted in morphological changes (irregular shape, pseudopodia) and
      aggregation of cells, comparable to changes observed in M-CSF/IFNgamma
      differentiated macrophages. Surface marker expression was altered after 24 h with
      an upregulation of CD14 (mean 2.5 fold) and CD64 (1.9 fold) in CSN1S1 stimulated
      cells. CSN1S1 treated cells showed a characteristic surface marker pattern for
      macrophages after 120 h of incubation (CD14high, CD64high, CD83low, CD1alow)
      comparable to changes observed in M-CSF/IFNgamma treated monocytes. Furthermore,
      phagocytic activity was increased 1.4 and 1.9 fold following stimulation with 10
      MUg/ml CSN1S1 after 24 and 48 h, respectively. Early GM-CSF, but not GM-CSF/IL-4
      induced differentiation of monocytes towards dendritic cells (DC) was inhibited
      by addition of CSN1S1. Finally, CSN1S1 induced upregulation of CD14 was impeded
      by inhibition of ERK1/2, while inhibition of the mitogen activated protein
      kinases JNK and p38 did not influence cellular differentiation. However, JNK and
      p38 inhibitors impeded CSN1S1 induced secretion of the proinflammatory cytokines
      IL-1b or IL-6. CONCLUSIONS: CSN1S1 skews in vitro differentiation of monocytes
      towards a macrophage-like phenotype. Data is accumulating that functions of
      CSN1S1 are beyond nutritional properties and include immunomodulatory effects.

PMID- 24083468
TI  - Ligand-field theory-based analysis of the adsorption properties of ruthenium
      nanoparticles.
AB  - The experimental design of improved nanocatalysts is usually based on shape
      control and is surface-ligand dependent. First-principle calculations can guide
      their design, both in terms of activity and selectivity, provided that
      theoretical descriptors can be defined and used in a prescreening process. As a
      consequence of the Sabatier principle and of the Bronsted-Evans-Polanyi
      relationship, an important prerequisite before optimizing the catalytic
      properties of nanoparticles is the knowledge of the selective adsorption
      strengths of reactants at their surface. We report here adsorption energies of X
      (H, CH3) and L (PH3, CO) ligands at the surface of bare ruthenium nanoclusters
      Run (n = 55 and 147) calculated at the DFT level. Their dependence on the
      topology of the adsorption sites as well as on the size and shape of the
      nanoparticles (NPs) is rationalized with local descriptors derived from the so
      called d-band center model. Defining the descriptors involves the determination
      of the energy of effective d atomic orbitals for each surface atom. Such a ligand
      field theory-like model is in close relation with frontier molecular orbital
      theory, a cornerstone of rational chemical synthesis. The descriptors are
      depicted as color maps which straightforwardly yield possible reactivity spots.
      The adsorption map of a large spherical hcp cluster (Ru288) nicely confirms the
      remarkable activity of steps, the so-called B5 sites. The predictive character of
      this conceptual DFT approach should apply to other transition metal NPs and it
      could be a useful guide to the design of efficient nanocatalysts bearing sites
      with a specific activity. 

PMID- 24083469
TI  - Synthesis of vinylogous amides by gold(I)-catalyzed cyclization of N-Boc
      protected 6-alkynyl-3,4-dihydro-2H-pyridines.
AB  - The gold(I)-catalyzed cyclization of N-Boc-protected 6-alkynyl-3,4-dihydro-2H
      pyridines, prepared by the Sonogashira coupling of lactam-derived enol triflates
      or phosphates, provides vinylogous amides, which are useful intermediates in the
      synthesis of natural compounds. The Au(I)-catalyzed reaction is carried out with
      Ph3PAuOTf as a catalyst and proceeds via a 6-endo-dig cyclization to form a
      vinylgold species that after protodeauration generates a cyclic carbamate
      intermediate. This intermediate is in most cases not isolated, but the addition
      of a base to the reaction mixture rapidly and quantitatively delivers the target
      vinylogous amide. The first synthesis of a natural compound from Sonneratia
      hainanensis has been accomplished by this approach. 

PMID- 24083470
TI  - Development and evaluation of the feasibility and effects on staff, patients, and
      families of a new tool, the Psychosocial Assessment and Communication Evaluation
      (PACE), to improve communication and palliative care in intensive care and during
      clinical uncertainty.
AB  - BACKGROUND: There are widespread concerns about communication and support for
      patients and families, especially when they face clinical uncertainty, a
      situation most marked in intensive care units (ICUs). Therefore, we aimed to
      develop and evaluate an interventional tool to improve communication and
      palliative care, using the ICU as an example of where this is difficult. METHODS:
      Our design was a phase I-II study following the Medical Research Council Guidance
      for the Development and Evaluation of Complex Interventions and the (Methods of
      Researching End-of-life Care (MORECare) statement. In two ICUs, with over 1900
      admissions annually, phase I modeled a new intervention comprising implementation
      training and an assessment tool. We conducted a literature review, qualitative
      interviews, and focus groups with 40 staff and 13 family members. This resulted
      in the new tool, the Psychosocial Assessment and Communication Evaluation (PACE).
      Phase II evaluated the feasibility and effects of PACE, using observation, record
      audit, and surveys of staff and family members. Qualitative data were analyzed
      using the framework approach. The statistical tests used on quantitative data
      were t-tests (for normally distributed characteristics), the chi2 or Fisher's
      exact test (for non-normally distributed characteristics) and the Mann-Whitney U
      test (for experience assessments) to compare the characteristics and experience
      for cases with and without PACE recorded. RESULTS: PACE provides individualized
      assessments of all patients entering the ICU. It is completed within 24 to 48
      hours of admission, and covers five aspects (key relationships, social details
      and needs, patient preferences, communication and information status, and other
      concerns), followed by recording of an ongoing communication evaluation.
      Implementation is supported by a training program with specialist palliative
      care. A post-implementation survey of 95 ICU staff found that 89% rated PACE
      assessment as very or generally useful. Of 213 family members, 165 (78%)
      responded to their survey, and two-thirds had PACE completed. Those for whom PACE
      was completed reported significantly higher satisfaction with symptom control,
      and the honesty and consistency of information from staff (Mann-Whitney U-test
      ranged from 616 to 1247, P-values ranged from 0.041 to 0.010) compared with those
      who did not. CONCLUSIONS: PACE is a feasible interventional tool that has the
      potential to improve communication, information consistency, and family
      perceptions of symptom control.

PMID- 24083471
TI  - Characteristic analysis of alpha-fetoprotein-producing gastric carcinoma in
      China.
AB  - alpha-Fetoprotein-producing gastric cancer (AFPGC) is a rare type of gastric
      cancer. The largest population of patients with AFPGC is found in China. In the
      present study, a total of 4,779 GC patients, including 317 AFPGC patients, from
      11 clinical studies in China with a general AFPGC/GC ratio of 6.63% were
      summarized and analyzed. On the basis of analysis of the clinical data, the
      patients with AFPGC had larger tumor size, weaker cell differentiation, worse
      histopathological types, deeper serosal infiltration, more lymph node and liver
      metastases, poorer stages, shorter survival time and more positive expression of
      vascular endothelial growth factors than the patients without AFPGC. Our
      observation is consistent with previous results reported in studies of AFPGC.
      Overall, AFPGC is a subtype of GC with a poor prognosis. 

PMID- 24083472
TI  - Risk assessment before allogeneic hematopoietic cell transplantation for older
      adults with acute myeloid leukemia.
AB  - Acute myeloid leukemia (AML) most commonly affects patients older than 60 years.
      Outcomes of treatment of older AML patients have been poor. The advent of reduced
      intensity conditioning (RIC) regimens made allogeneic hematopoietic cell
      transplantation (HCT) an available treatment option with curative intent for
      older AML patients. Because older patients are often excluded from clinical
      trials, little is known about the stratification of their risks before allogeneic
      HCT. While recent studies of RIC and allogeneic HCT have shown little impact of
      age on outcomes, other variables such as the recipient health status and the AML
      disease status and chromosomal aberrations have proven to be of prognostic
      significance. Here, the authors review recent studies of allogeneic HCT for older
      patients with AML with detailed evaluation of risk factors for relapse as well as
      non-relapse mortality. The authors have integrated the currently available
      information on transplant risks into a five-category risk-benefit system that
      could aid in the decision-making in this patient population. 

PMID- 24083473
TI  - Stroke prevention in atrial fibrillation in older adults: existing knowledge gaps
      and areas for innovation: a summary of an American Federation for Aging research
      seminar.
AB  - Atrial fibrillation (AF) is a common and morbid cardiac arrhythmia that increases
      in prevalence with advancing age. The risk of ischemic stroke, a primary and
      disabling hazard of AF, also increases with advancing age. The aging of the
      population is anticipated to contribute to a rising burden of AF-related
      morbidity and economic costs, given the close association between the arrhythmia
      and aging. Recent biological, diagnostic, and therapeutic developments raise hope
      that AF-related stroke can be largely prevented, yet despite advances in stroke
      prevention for individuals with AF, numerous scientific and clinical knowledge
      gaps remain, particularly as these developments are applied to older adults.
      Given the public health importance of AF-related stroke in elderly adults, a
      group of clinician-investigators convened on April 5, 2012, to identify promising
      areas for investigation that may ultimately reduce stroke-related morbidity. This
      article summarizes the meeting discussion and emphasizes innovative topic areas
      that may ultimately facilitate the application of novel preventive, diagnostic,
      and therapeutic insights into the management of older adults with AF. The
      opinions of those that participated in the meeting limit this report, which may
      not represent all of the questions that other experts in this field might raise. 

PMID- 24083474
TI  - Heparan sulfate mediates trastuzumab effect in breast cancer cells.
AB  - BACKGROUND: Trastuzumab is an antibody widely used in the treatment of breast
      cancer cases that test positive for the human epidermal growth factor receptor 2
      (HER2). Many patients, however, become resistant to this antibody, whose
      resistance has become a major focus in breast cancer research. But despite this
      interest, there are still no reliable markers that can be used to identify
      resistant patients. A possible role of several extracellular matrix (ECM)
      components--heparan sulfate (HS), Syn-1(Syndecan-1) and heparanase (HPSE1)--in
      light of the influence of ECM alterations on the action of several compounds on
      the cells and cancer development, was therefore investigated in breast cancer
      cell resistance to trastuzumab. METHODS: The cDNA of the enzyme responsible for
      cleaving HS chains from proteoglycans, HPSE1, was cloned in the pEGFP-N1 plasmid
      and transfected into a breast cancer cell lineage. We evaluated cell viability
      after trastuzumab treatment using different breast cancer cell lines. Trastuzumab
      and HS interaction was investigated by confocal microscopy and Fluorescence
      Resonance Energy Transfer (FRET). The profile of sulfated glycosaminoglycans was
      also investigated by [35S]-sulfate incorporation. Quantitative RT-PCR and
      immunofluorescence were used to evaluate HPSE1, HER2 and Syn-1 mRNA expression.
      HPSE1 enzymatic activity was performed using biotinylated heparan sulfate.
      RESULTS: Breast cancer cell lines responsive to trastuzumab present higher
      amounts of HER2, Syn-1 and HS on the cell surface, but lower levels of secreted
      HS. Trastuzumab and HS interaction was proven by FRET analysis. The addition of
      anti-HS to the cells or heparin to the culture medium induced resistance to
      trastuzumab in breast cancer cells previously sensitive to this monoclonal
      antibody. Breast cancer cells transfected with HPSE1 became resistant to
      trastuzumab, showing lower levels of HER2, Syn-1 and HS on the cell surface. In
      addition, HS shedding was increased significantly in these resistant cells.
      CONCLUSION: Trastuzumab action is dependent on the availability of heparan
      sulfate on the surface of breast cancer cells. Furthermore, our data suggest that
      high levels of heparan sulfate shed to the medium are able to capture
      trastuzumab, blocking the antibody action mediated by HER2. In addition to HER2
      levels, heparan sulfate synthesis and shedding determine breast cancer cell
      susceptibility to trastuzumab.

PMID- 24083475
TI  - Application of proteomics to identify the target molecules involved in Lonicera
      japonica-induced photokilling in human lung cancer CH27 cells.
AB  - BACKGROUND: The Lonicera japonica has been used as natural and healthy drink for
      its anti-inflammatory effect and pleasant odor in China and Taiwan. METHODS: 2D
      electrophoresis was used to analyze the proteins involved in photoactivated
      Lonicera japonica-induced CH27 cell apoptosis. The fluorescent dyes MitoTracker
      Red CMXRos, calcein AM and JC-1 were used to elucidate mitochondrial function.
      The protein expression was performed by Western blotting. Fluorescent image of
      endoplasmic reticulum was accomplished by using ER-Tracker Green. This study used
      fluorescent dye CM-H2DCFDA to detect intracellular generation of reactive oxygen
      species. RESULTS: The identified proteins can be classified into three major
      groups, which include proteins involved in mitochondrial function, cytoskeleton
      related proteins and proteins associated with endoplasmic reticulum (ER) stress.
      Photoactivated Lonicera japonica caused a significant effect on the mitochondrial
      function and ER stress in CH27 cells. The reactive oxygen species producing was
      found to be involved in photoactivated Lonicera japonica-induced CH27 cell
      apoptosis. CONCLUSION: Mitochondria and endoplasmic reticulum are the integral
      targets in photoactivated Lonicera japonica-induced CH27 cell apoptosis. We also
      demonstrated that ethyl acetate fraction of Lonicera japonica extracts caused
      photocytotoxicity in a dose-dependent manner in CH27 cells. This could explain
      the fact that the ethyl acetate fraction of Lonicera japonica extracts may
      contain compounds which exhibit the photosensitizing activity in CH27 cells.

PMID- 24083476
TI  - Integrated microscale analysis system for targeted liquid chromatography mass
      spectrometry proteomics on limited amounts of enriched cell populations.
AB  - Limited samples, such as those that are in vivo sourced via biopsy, are closely
      representative of biological systems and contain valuable information for drug
      discovery. However, these precious samples are often heterogeneous and require
      cellular prefractionation prior to proteomic analysis to isolate specific
      subpopulations of interest. Enriched cells from in vivo samples are often very
      limited (<10(4) cells) and pose a significant challenge to proteomic nanoliquid
      chromatography mass spectrometry (nanoLCMS) sample preparation. To enable the
      streamlined analysis of these limited samples, we have developed an online cell
      enrichment, microscale sample preparation, nanoLCMS proteomics workflow by
      integrating fluorescence activated cell sorting (FACS), focused ultrasonication,
      microfluidics, immobilized trypsin digestion, and nanoLCMS. To assess the
      performance of the online FACS-Chip-LCMS workflow, 5000 fluorescent labeled cells
      were enriched from a 5% heterogeneous cell population and processed for LCMS
      proteomics in less than 2 h. Within these 5000 enriched cells, 30 peptides
      corresponding to 17 proteins spanning more than 4 orders of magnitude of cellular
      abundance were quantified using a QExactive MS. The results from the online FACS
      Chip-LCMS workflow starting from 5000 enriched cells were directly compared to
      results from a traditional macroscale sample preparation workflow starting from
      2.0 * 10(6) cells. The microscale FACS-Chip-LCMS workflow demonstrated high
      cellular enrichment efficiency and high peptide recovery across the wide dynamic
      range of targeted peptides. Overall the microscale FACS-Chip-LCMS workflow has
      shown effectiveness in efficiently preparing limited amounts of FACS enriched
      cells in an online manner for proteomic LCMS. 

PMID- 24083478
TI  - ESIPT and photodissociation of 3-hydroxychromone in solution: photoinduced
      processes studied by static and time-resolved UV/Vis, fluorescence, and IR
      spectroscopy.
AB  - The spectral properties of fluorescence sensors such as 3-hydroxychromone (3-HC)
      and its derivatives are sensitive to interaction with the surrounding medium as
      well as to substitution. 3-HC is a prototype system for other derivatives because
      it is the basic unit of all flavonoides undergoing ESIPT and is not perturbed by
      a substituent. In this study, the elementary processes and intermediate states in
      the photocycle of 3-HC as well as its anion were identified and characterized by
      the use of static and femtosecond time-resolved spectroscopy in different
      solvents (methylcyclohexane, acetonitrile, ethanol, and water at different pH).
      Electronic absorption and fluorescence spectra and lifetimes of the intermediate
      states were obtained for the normal, tautomer and anionic excited state, while
      mid-IR vibrational spectra yielded structural information on ground and excited
      states of 3-HC. A high sensitivity on hydrogen-bonding perturbations was
      observed, leading to photoinduced anion formation in water, while in organic
      solvents, different processes are suggested, including slow picosecond ESIPT and
      contribution of the trans-structure excited state or a different stable solvation
      state with different direction of OH. The formation of the latter could be
      favored by the lack of a substituent increasing contact points for specific
      solute-solvent interactions at the hydroxyl group compared to substituted
      derivatives. The effect of substituents has to be considered for the design of
      future fluorescence sensors based on 3-HC. 

PMID- 24083477
TI  - Cold Atmospheric Plasma: methods of production and application in dentistry and
      oncology.
AB  - Cold Atmospheric Plasma is an ionized gas that has recently been extensively
      studied by researchers as a possible therapy in dentistry and oncology. Several
      different gases can be used to produce Cold Atmospheric Plasma such as Helium,
      Argon, Nitrogen, Heliox, and air. There are many methods of production by which
      cold atmospheric plasma is created. Each unique method can be used in different
      biomedical areas. In dentistry, researchers have mostly investigated the
      antimicrobial effects produced by plasma as a means to remove dental biofilms and
      eradicate oral pathogens. It has been shown that reactive oxidative species,
      charged particles, and UV photons play the main role. Cold Atmospheric Plasma has
      also found a minor, but important role in tooth whitening and composite
      restoration. Furthermore, it has been demonstrated that Cold Atmospheric Plasma
      induces apoptosis, necrosis, cell detachment, and senescence by disrupting the S
      phase of cell replication in tumor cells. This unique finding opens up its
      potential therapy in oncology. 

PMID- 24083479
TI  - Highly selective detection of polycyclic aromatic hydrocarbons using
      multifunctional magnetic-luminescent molecularly imprinted polymers.
AB  - A facile method is presented for the selective luminescence detection of trace
      polycyclic aromatic hydrocarbons (PAHs) based on a combination of the specific
      recognition of molecularly imprinted polymers (MIPs) and magnetic separation
      (MS). Multifunctional magnetic-luminescent MIP nanocomposites were fabricated via
      a one-pot emulsion strategy using polystyrene-co-methacrylic acid copolymer,
      hydrophobic Fe3O4 nanoparticles and luminescent LaVO4:Eu(3+) nanoparticles as
      building blocks with a phenanthrene template. The resulting nanocomposites can be
      employed in a simple method for the luminescence detection of phenanthrene.
      Furthermore, magnetic separation of the nanocomposites from the target mixture
      prior to luminescence detection of phenanthrene affords significantly enhanced
      selectivity and sensitivity, with a 3sigma limit of detection (LOD) as low as
      3.64 ng/mL. Milk samples spiked with phenanthrene (5.0 MUg/mL) were assayed via
      this method and recoveries ranging from 97.11 to 101.9% were obtained, showing
      that our strategy is potentially applicable for the preconcentration, recovering,
      and monitoring of trace PAHs in complex mixtures. 

PMID- 24083480
TI  - The placenta findings from an XYY abortus: a case report.
AB  - INTRODUCTION: The placenta morphology from an XYY pregnancy abortus has not been
      reported in the medical literature. This case report consists of the first
      detailed documentation. The reported case is also highly unusual because the
      mother had two prior pregnancies with fetuses being confirmed to have Zellweger
      syndrome and one prior molar pregnancy. CASE PRESENTATION: A 43-year-old
      Caucasian woman presented for induction of labor secondary to diagnosis of XYY
      chromosomes by chorionic villus sample. CONCLUSIONS: This is the first detailed
      observation of placenta morphology in an XYY abortus. Although not highly
      specific, the observation is very unique and should prompt further investigation
      of karyotyping of the fetus or infant because an XYY individual may be viable and
      grow to adulthood. The association of an XYY abortus and prior pregnancies with
      Zellweger syndrome and one prior molar pregnancy is also highly notable.

PMID- 24083481
TI  - Blood plasma levels of microelements in patients with history of optic neuritis.
AB  - PURPOSE: To determine the concentration of microelements in the blood of patients
      with a history of retrobulbar optic neuritis (ON). MATERIALS AND METHODS: We
      examined 36 patients (18-63 years of age) - 11 with demyelinating ON (Group 1)
      and 25 with isolated ON (Group 2) - all of whom had been treated for retrobulbar
      ON. The control group comprised 38 healthy volunteers. Using atomic absorption
      spectroscopy, blood levels of zinc (Zn), iron (Fe), copper (Cu) and cadmium (Cd)
      were evaluated. RESULTS: Compared with the control group, concentrations of Cd
      were elevated in Groups 1 and 2 (p = 0.003 and p = 0.003, respectively); Group 1
      had higher levels of Cu (p = 0.02). Patients from both groups had significantly
      lower levels of Fe (p = 0.0003) compared with controls. No difference in the
      concentration of any of the microelements was found between Groups 1 and 2.
      CONCLUSION: Disturbances in Cd, Cu and Fe homeostasis may be associated with the
      inflammatory process of ON.

PMID- 24083482
TI  - Antioxidant and anti-inflammatory effects of exercise: role of redox signaling.
AB  - Contraction-induced production of reactive oxygen species (ROS) has been
      implicated in oxidative stress to skeletal muscle for the past few decades. As
      research advances more evidence has revealed a more complete role of ROS under
      both physiological and pathological conditions. The current review postulated
      that moderate intensity of physical exercise has antioxidant and anti
      inflammatory effects due to the operation and cross-talks of several redox
      sensitive signal transduction pathways. The functional roles and mechanisms of
      action of the nuclear factor kappaB, mitogen-activated protein kinase, and
      peroxisome proliferator-activated receptor gamma co-activator 1alpha are
      highlighted.

PMID- 24083483
TI  - Cell penetrating peptide conjugated polymeric micelles as a high performance
      versatile nonviral gene carrier.
AB  - The major goal of this study is to design, synthesize, and evaluate linoleic acid
      and penetratin dual-functionalized chitosan (CS-Lin-Pen) as a nonviral gene
      carrier. The amphiphilic CS-Lin-Pen self-assembles to form cationic micelles in
      an aqueous environment. These polymeric micelles exhibited excellent
      hemocompatibility and cell viability, as evaluated by in vitro hemolysis and MTT
      assay, respectively. When CS-Lin-Pen micelles were added to plasmid DNA (pDNA)
      solution, the electrostatic interaction between the cationic micelles and anionic
      pDNA led to the formation of stable CS-Lin-Pen/pDNA polyplexes with ~100 nm in
      size. The resultant polyplexes demonstrated ~5-fold higher cellular uptake as
      compared to unmodified chitosan. Furthermore, CS-Lin-Pen micelles showed
      efficient protection of pDNA from DNase I attack and exhibited ~34-40-fold higher
      transfection in comparison with unmodified chitosan in HEK 293, CHO, and HeLa
      cells. These findings illustrate that the CS-Lin-Pen micelles could be exploited
      as a potential nonviral vector for efficient gene therapy.

PMID- 24083484
TI  - Antigenotoxic effect of Tartary (Fagopyrum tataricum) and common (Fagopyrum
      esculentum) buckwheat flour.
AB  - The aim of our work was to determine and to compare the possible antigenotoxic
      effect of methanolic extracts of common buckwheat (CB) and Tartary buckwheat (TB)
      flour, containing naturally present rutin (R), and quercetin (Q), and of R and Q
      in chemical form, against tert-butyl hydroperoxide (t-BOOH) induced DNA damage in
      human hepatoma cell line (HepG2). R and Q content of CB and TB flour extracts was
      determined by reversed phase-high performance liquid chromatography and
      antigenotoxic effect of flour extracts, R and Q was evaluated using the comet
      assay. R (100 MUM) and Q (50 MUM) decreased the extent of t-BOOH induced DNA
      damage for 51% and 67%, respectively. CB and TB flour extracts showed high
      antioxidant capacity and prominent genoprotective ability. CB extract containing
      up to 0.1 MUM R decreased t-BOOH induced DNA damage for 34%, and TB extract
      containing up to 12.64 MUM R, and 2.86 MUM Q for 40%. The obtained results show
      high antigenotoxic activity of buckwheat and furthermore, they suggest that
      complex nutrient and flavonoid rich food products are more efficient in their
      health promoting effects compared to a single active substance.

PMID- 24083485
TI  - Water types and their relaxation behavior in partially rehydrated CaFe-mixed
      binary oxide obtained from CaFe-layered double hydroxide in the 155-298 K
      temperature range.
AB  - Heat-treated CaFe-layered double hydroxide samples were equilibrated under
      conditions of various relative humidities (11%, 43% and 75%). Measurements by FT
      IR and dielectric relaxation spectroscopies revealed that partial to full
      reconstruction of the layered structure took place. Water types taking part in
      the reconstruction process were identified via dielectric relaxation measurements
      either at 298 K or on the flash-cooled (to 155 K) samples. The dynamics of water
      molecules at the various positions was also studied by this method, allowing the
      flash-cooled samples to warm up to 298 K. 

PMID- 24083486
TI  - Discrimination of infectious hepatitis A virus and rotavirus by combining dyes
      and surfactants with RT-qPCR.
AB  - BACKGROUND: Human enteric viruses are major agents of foodborne diseases. Because
      of the absence of a reliable cell culture method for most of the enteric viruses
      involved in outbreaks, real-time reverse transcriptase PCR is now widely used for
      the detection of RNA viruses in food samples. However this approach detects viral
      nucleic acids of both infectious and non infectious viruses, which limits the
      impact of conclusions with regard to public health concern. The aim of the study
      was to develop a method to discriminate between infectious and non-infectious
      particles of hepatitis A virus (HAV) and two strains of rotavirus (RV) following
      thermal inactivation by using intercalating dyes combined with RT-qPCR. RESULTS:
      Once the binding of propidium monoazide (PMA) or ethidium monoazide (EMA) was
      shown to be effective on the viral ssRNA of HAV and dsRNA of two strains of RV
      (SA11 and Wa), their use in conjunction with three surfactants (IGEPAL CA-630,
      Tween 20, Triton X-100) prior to RT-qPCR assays was evaluated to quantify the
      infectious particles remaining following heat treatment. The most promising
      conditions were EMA (20 MUM) and IGEPAL CA-630 (0.5%) for HAV, EMA (20 MUM) for
      RV (WA) and PMA (50 MUM) for RV (SA11). The effectiveness of the pre-treatment RT
      qPCR developed for each virus was evaluated with three RT-qPCR assays (A, B, C)
      during thermal inactivation kinetics (at 37 degrees C, 68 C, 72 degrees C, 80
      degrees C) through comparison with data obtained by RT-qPCR and by infectious
      titration in cell culture. At 37 degrees C, the quantity of virus (RV, HAV)
      remained constant regardless of the method used. The genomic titers following
      heat treatment at 68 degrees C to 80 degrees C became similar to the infectious
      titers only when a pre-treatment RT-qPCR was used. Moreover, the most effective
      decrease was obtained by RT-qPCR assay A or B for HAV and RT-qPCR assay B or C
      for RV. CONCLUSIONS: We concluded that effectiveness of the pre-treatment RT-qPCR
      is influenced by the viral target and by the choice of the RT-qPCR assay.
      Currently, it would be appropriate to further develop this approach under
      specific conditions of inactivation for the identification of infectious viruses
      in food and environmental samples.

PMID- 24083487
TI  - Seasonal variability in bacterial and fungal diversity of the near-surface
      atmosphere.
AB  - Bacteria and fungi are ubiquitous throughout the Earth's lower atmosphere where
      they often represent an important component of atmospheric aerosols with the
      potential to impact human health and atmospheric dynamics. However, the
      diversity, composition, and spatiotemporal dynamics of these airborne microbes
      remain poorly understood. We performed a comprehensive analysis of airborne
      microbes across two aerosol size fractions at urban and rural sites in the
      Colorado Front Range over a 14-month period. Coarse (PM10-2.5) and fine (PM2.5)
      particulate matter samples were collected at weekly intervals with both bacterial
      and fungal diversity assessed via high-throughput sequencing. The diversity and
      composition of the airborne communities varied across the sites, between the two
      size fractions, and over time. Bacteria were the dominant type of bioaerosol in
      the collected air samples, while fungi and plants (pollen) made up the remainder,
      with the relative abundances of fungi peaking during the spring and summer
      months. As bacteria made up the majority of bioaerosol particles, we analyzed the
      bacterial communities in greater detail using a bacterial-specific 16S rRNA gene
      sequencing approach. Overall, bacterial taxonomic richness and the relative
      abundances of specific bacterial taxa exhibited significant patterns of
      seasonality. Likewise, airborne bacterial communities varied significantly
      between sites and across aerosol size fractions. Source-tracking analyses
      indicate that soils and leaves represented important sources of bacteria to the
      near-surface atmosphere across all locations with cow fecal bacteria also
      representing an important source of bioaerosols at the more rural sites during
      early fall and early spring. Together, these data suggest that a complex set of
      environmental factors, including changes in atmospheric conditions and shifts in
      the relative importance of available microbial sources, act to control the
      composition of microbial bioaerosols in rural and urban environments. 

PMID- 24083488
TI  - All-polymer solar cells with 3.3% efficiency based on naphthalene diimide
      selenophene copolymer acceptor.
AB  - The lack of suitable acceptor (n-type) polymers has limited the photocurrent and
      efficiency of polymer/polymer bulk heterojunction (BHJ) solar cells. Here, we
      report an evaluation of three naphthalene diimide (NDI) copolymers as electron
      acceptors in BHJ solar cells which finds that all-polymer solar cells based on an
      NDI-selenophene copolymer (PNDIS-HD) acceptor and a thiazolothiazole copolymer
      (PSEHTT) donor exhibit a record 3.3% power conversion efficiency. The observed
      short circuit current density of 7.78 mA/cm(2) and external quantum efficiency of
      47% are also the best such photovoltaic parameters seen in all-polymer solar
      cells so far. This efficiency is comparable to the performance of similarly
      evaluated [6,6]-Phenyl-C61-butyric acid methyl ester (PC60BM)/PSEHTT devices. The
      lamellar crystalline morphology of PNDIS-HD, leading to balanced electron and
      hole transport in the polymer/polymer blend solar cells accounts for its good
      photovoltaic properties. 

PMID- 24083489
TI  - Stereoselective synthesis of amido and phenyl azabicyclic derivatives via a
      tandem aza Prins-Ritter/Friedel-Crafts type reaction of endocyclic N-acyliminium
      ions.
AB  - A simple protocol is described for the synthesis of amido and phenyl
      hexahydroindolizin-3(2H)-one, hexahydro-1H-quinolizin-4(6H)-one, and 1,3,4,10b
      tetrahydropyrido[2,1-a]isoindol-6(2H)-one derivatives via endo-trig (aza-Prins
      type) cyclization followed by an intermolecular Ritter/Friedel-Crafts reaction of
      cyclic N-acyliminium ions, which are derived from the boron trifluoride etherate
      treatment of regioselectively reduced N-homoallyl imides. The reactions are
      highly diastereoselective with excellent yields. 

PMID- 24083490
TI  - Oxidative synthesis of highly fluorescent boron/nitrogen co-doped carbon nanodots
      enabling detection of photosensitizer and carcinogenic dye.
AB  - Current research efforts have demonstrated the facile hydrothermal oxidative
      synthetic route to develop highly fluorescent boron/nitrogen co-doped carbon
      nanodots (CNDs). During this process, N-(4-hydroxyphenyl)glycine served as a
      source of N doping and a carbon precursor as well, while boric acid H3BO3 is used
      as an oxidizing agent in the N2 environment. Surface passivation through
      ultrasonic treatment of CNDs was performed to induce modifications by using
      various surface passivating agents. Polyethyleneimine (PEI) remarkably enhanced
      the fluorescence performance and monodispersity of polymerized carbon nanodots (P
      CNDs) in aqueous phase with an enhanced quantum yield of 23.71%, along with an
      increase in size from ~3 nm to ~200 nm. For characterization of CNDs and P-CNDs,
      UV, infrared, photoluminescence, transmission electron microscopy, x-ray
      photoelectron spectra, and atomic force microscopy techniques were utilized.
      Application potentials of synthesized P-CNDs were developed via introduction of
      protoporphyrin (PPD, a photosensitizer) which has great doping affinity with
      polymer PEI to switch-off the fluorescence of P-CNDs, leading to the production
      of dye-doped nanoprobes. Fluorescence resonance energy transfer (FRET) was also
      observed during dye-doping, and PPD was detected with a limit of detection (LOD,
      3sigma) of 15 pM. The fluorescence recovery of this switched-off nanoprobe was
      made possible by using Sudan red III (carcinogenic dye), which was oxidized by
      PPD doped in P-CNDs. Sudan red III was detected in the concentration range of 9.9
      pM-0.37 nM. Meanwhile, it was also confirmed that the dye-doped nanoprobe is
      highly selective and exceptionally sensitive to detect this carcinogenic agent in
      commercial products with a LOD (3sigma) of 90 fM.

PMID- 24083491
TI  - High-risk human papillomavirus (HPV) DNA sequences in metaplastic breast
      carcinomas of Mexican women.
AB  - BACKGROUND: Metaplastic carcinoma, an uncommon subtype of breast cancer, is part
      of the spectrum of basal-like, triple receptor-negative breast carcinomas. The
      present study examined 20 surgical specimens of metaplastic breast carcinomas,
      for the presence of high-risk Human papillomavirus (HPV), which is suspected to
      be a potential carcinogenic agent for breast carcinoma. METHODS: Mastectomy
      specimens from patients harboring metaplastic breast carcinoma, as defined by the
      World Health Organization (WHO), and who attended the Instituto Nacional de
      Cancerologia in Mexico City, were retrieved from the files of the Department of
      Pathology accumulated during a 16-year period (1995-2008). Demographic and
      clinical information was obtained from patients' medical records. DNA was
      extracted from formalin-fixed, paraffin-embedded tumors and HPV type-specific
      amplification was performed by means of Polymerase chain reaction (PCR).
      Quantitative Real-time (RT) PCR was conducted in HPV positive cases.
      Statistically, the association of continuous or categorical variables with HPV
      status was tested by the Student t, the Chi square, or Fisher's exact tests, as
      appropriate. RESULTS: High-risk HPV DNA was detected in eight (40%) of 20
      metaplastic breast carcinomas: seven (87.5%) HPV-16 and one (12.5%) HPV-18. Mean
      age of patients with HPV-positive cases was 49 years (range 24-72 years), the
      same as for HPV-negative cases (range, 30-73 years). There were not striking
      differences between HPV + and HPV- metaplastic carcinomas regarding clinical
      findings. Nearly all cases were negative for estrogen, progesterone and Human
      epidermal growth factor receptor 2 (HER2), but positive for Epidermal growth
      factor receptor (EGFR). CONCLUSIONS: High-risk HPV has been strongly associated
      with conventional breast carcinomas, although the subtle mechanism of neoplastic
      transformation is poorly understood. In Mexican patients, the prevalence of HPV
      infection among metaplastic breast carcinomas is higher than in non-metaplastic
      ones, as so the HPV viral loads; notwithstanding, HPV viral loads show wide
      variation and remain even lower than cervical and other non-cervical carcinomas,
      making it difficult to assume that HPV could play a key role in breast
      carcinogenesis. Further studies are warranted to elucidate the meaning of the
      presence of high-risk HPVDNA in breast carcinomas.

PMID- 24083492
TI  - Clear cell tumor of the lung: a case report and literature review.
AB  - Clear cell tumor of the lung is a rare and benign pulmonary tumor; only sporadic
      cases have been reported. Here, we report the case of a 38-year-old man with
      recurrent cough, blood-streaked sputum and left chest pain. A chest computed
      tomography scan showed a round, homogeneous pulmonary mass in the left lower
      lobe, which exhibited intense heterogeneous enhancement in the arterial phase and
      homogeneous in the delay phase after injecting a contrast agent. The patient
      underwent a fine-needle aspiration biopsy and was diagnosed as having a benign
      clear cell tumor of the lung. The clinical presentation and radiographic
      investigation of this tumor are summarized in this paper to recognize this rare
      disease. Interestingly, we found some differences with previously reported cases.

PMID- 24083493
TI  - [Measuring the impact of nursing on health: a literature review].
AB  - Measuring nursing contribution to health services' outcomes represents a primary
      issue for nursing research internationally. The aim of this literature review was
      to outline main research lines studying the effect of nursing practice on health.
      A search of the literature was performed asking health and nursing-specific major
      database and consulting websites of authoritative nursing associations and
      scientific societies. Four main nursing research lines were found in literature
      and they concerned, nurse staffing and patient and staff-related outcomes; level
      of nursing care needed to achieve attended outcomes in hospitals; practice
      environments and patient and staff-related outcomes; the use of nursing
      terminologies and classifications to describe nursing-specific and nursing
      sensitive outcomes. Although researchers report the need to strengthen available
      evidences, recommendations suggest to empower nurses and nursing in clinical,
      educational, organizational and policy-making settings in order to draw toward
      the best health outcomes for communities. 

PMID- 24083495
TI  - [Etiology and prevalence of chronic pain in adults: a narrative review].
AB  - The chronic nonmalignant pain is an underestimated epidemiologic health problem.
      It is a disease in its own right. It is one of the major reasons because patients
      use health service. The magnitude of chronic pain is in terms of human suffering
      and costs to society. The aim of this review is to identify the diagnosis and the
      prevalence of nonmalignant chronic pain in the adults. We have done a review of
      the literature from 1998 to 2012 using the virtual newspaper libraries starting
      from data bases (Pub-Med, CINAHL, Cochrane). We have made a narrative review of
      the articles obtained. Excluding topics of headache, pain for pediatric and
      geriatric groups, cancer pain and disease-specific items. Studies were classified
      for year, author sample, methods, age groups and definition of pain. We have
      obtained 7 articles. These epidemiological studies conducted in different part of
      the world, reported prevalence rates of chronic pain ranging from 16-53%. They
      shows a high heterogeneity of results concerning diagnosis and methods. Although
      limited the number of articles, show the high complexity of the phenomenon. 

PMID- 24083494
TI  - [Intercultural nursing: analysis of changes in the perception of relational
      problems with foreign patients].
AB  - Today's society is highly impacted by immigration, as well as healthcare system.
      It is becoming increasingly common and frequent to establish relationships with
      patients with different cultural backgrounds. The aim of this study is analyzing
      Italian nurses' perception of the relational dynamics with foreign patients, to
      determine its evolution, and to identify the variables which can affect the
      quality of care. The study is both qualitative and quantitative with descriptive
      aim, using a questionnaire that assesses the theoretical-practical level of
      preparation, both perceptive and effective, of nurses when assisting foreign
      patients. To evaluate the emotional and experiential impact of the relationship
      with foreign patients, the difficulties encountered while establishing such
      relationship, and the resolution strategies - both effective and potential. The
      sample, composed of 101 Italian nurses employed at SanRaffaele Hospital in 6
      specific Operational Units, resulted in a total of 91 returned questionnaires
      during the period May-June 2011. The data was analyzed through statistical
      instruments and compared to the results of a similar study done in 2004. The
      experience of intercultural nursing is seen by the sample as interesting and
      rewarding. The vast majority of nurses have positive responses. The more frequent
      issues are those connected with communication with foreign patients, and those
      connected with the increase workload due the presence of foreign patients. Nurses
      responded to difficulties more with human skills than with specific abilities,
      and tend to delegate the problem to the Cultural Mediation service. This new
      issue has a very high impact on nurses. The emerged difficulties have not
      decreased over time, this due to the lack of a proper policy within health care
      facilities in recent years, with the exception of a little improvement on the
      academic education. However the current academic education does not provide
      solutions useful in the everyday routing. This study, despite the small sample
      and a rather narrow degree of analysis, likes to draw attention on the topic both
      of nurses and on health care facilities managerial team in order to develop a
      effective startegie to deal with the emerged issues. 

PMID- 24083496
TI  - [To know to change: the nurses of the Oncology Institute of Southern Switzerland
      (IOSI) and their relationship with the Evidence Based Practise (EBP) and Nursing
      Research].
AB  - To promote the development of a culture and a professional practice based on
      "evidence of effectiveness", the IOSI Nursing Officer instituted a specific Unit
      which decided to establish its own lines of action based on the results of an
      internal investigation conducted among nurses employed within IOSI, with
      reference to the model of action research. In July 2010, a semi-structured
      questionnaire self compiled was sent to all nurses to find out their opinions and
      experiences on EBP and nursing research, to recognize their proposals, and
      willingness to be part of an internal network. 63 out of 98 questionnaire were
      filled in. Several nurses have knowledge and experience in these fields, but
      change their professional behavior especially under pressure from the external
      environment, rather than by autonomous choice. They consider EBP substantially
      useful, but difficult to implement especially without their direct involvement.
      Two third of the sample have felt the need of EBP during their professional
      activity and there is a general willingness to develop nursing research (56%)
      and/or play an active role of "referent" on these issues within own Unit (35%).
      The survey showed that at IOSI there is a favorable substrate for EBP and nursing
      research (for basic knowledge and availability). The data collected have served
      to define internal lines of action in a narrow relationship with the clinical
      areas, according to the model of action research. It is a process that requires
      vision, coordinated efforts, perseverance and time. 

PMID- 24083497
TI  - [Assessment and choice of the device for vascular access].
AB  - The accurate vascular monitoring by nurses both at the beginning and during
      infusion treatment, in addition to the selection of the best device for each
      patient, can increase patient satisfaction, reduce complications, preserve
      peripheral veins, reduce or eliminate time used to find unlikely vein access,
      reduce hospital stay length and reduce the costs associated with infusion
      treatment. Aims of study are to ascertain the presence of a procedure for
      choosing the most suitable venous device for each patient, to identify nurses'
      criteria to make a vascular assessment, and to describe when nurses make a
      vascular assessment. A descriptive study with convenience sample of 290 nurses.
      The data collection instrument is an anonymous questionnaire. The questionnaires
      administered, returned, and considered valid were 227. 14% of the sample states
      that within their ward there is a a procedure to evaluate the most suitable
      device, while 70% states the opposite and 16% of the sample states that "they do
      not know". The results show fairly clearly that in the wards considered there is
      no procedure currently in use in order to choose the most suitable device for
      each patient, that nurses do not have clear criteria to make a vascular
      assessment, that they carry out vascular assessment at different times of the
      infusion's process. 

PMID- 24083498
TI  - ['See and Treat' in the Emergency Department: legal aspects and professional
      nursing responsibility].
AB  - The article aim to analyze the legal aspects of professional responsibility in
      the autonomous nursing care of a patient with a minor health problem treated in a
      See and Treat area of the Emergency Department through a literature review and an
      analyses of the Italian legislation about professional exercise. Recent studies
      have shown that the treatment of the emergency patients affected by minor health
      problems in separated areas of the A&E by skilled nurses proved to be effective
      in reducing time to medical examination and the overall time spent in the
      Emergency Department. Several studies have shown the positive effects of the
      Emergency Nurse Practitioner (ENP) in terms of reduction of time to medical
      examination with an increase in patient satisfaction, maintaining an adequate
      level of quality in the care of patients with minor health problems. The
      introduction of a See and Treat area, together with the institution of advanced
      post-triage protocols, represents a possible answer to the overcrowding of the
      Emergency Department. The aim is the reduction of waiting times and proper
      allocation of both material and professional resources. The "See and Treat" nurse
      represents an expert nurse, with an adequate level of competence, who acts in
      respect to the clinical protocols shared between physicians and nurses. The
      Italian legislation is not in contrast with the introduction of the See and Treat
      nurse, on the contrary it offers opportunities for further professional
      development. 

PMID- 24083499
TI  - Anatomy and physiology for nursing students: is problem-based learning effective?
AB  - This study investigated whether problem-based learning (PBL) was an effective
      strategy for nursing students learning anatomy and physiology. Anatomy and
      physiology are subject areas that have posed long standing difficulty for nursing
      students. Since anatomy and physiology underpin clinical decision making it is
      important that nursing students are able to understand and retain this knowledge
      and apply it to practice. Problem-based learning offers potential advantages for
      teaching anatomy and physiology as clinical cases can provide the impetus for
      student problem solving. This project trialled a simple PBL scenario and
      investigated students' response to the task of problem solving in a laboratory
      setting adapted to simulate a hospital ward. The study found students learn
      better, retain the knowledge and merge theory with simulated practice when a PBL
      teaching mode is used. While PBL was effective, blended, web based and hybrid PBL
      models warrant investigation. 

PMID- 24083500
TI  - Nurses: advocating, leading, caring!
AB  - This speech was delivered on 27 October at the 2012 Conference and general
      meeting of the Italian Nurses Association CNAI (Consociazione nazionale delle
      Associazioni infermiere/i) held in Rome from 25 to 27 October 2012. The theme of
      the conference was "No Nurses No Future". The "No Nurses No Future" is a national
      campaign developed by the nurses of the Italian Nurses Association to fight for
      the rights of the profession to sustain not only the practice of the nurse,
      strong nursing education, research and regulation, but more importantly to ensure
      that in the future there will be enough nurses in the healthcare workforce to
      advocate, lead and care for the citizens of Italy.Italian nurses took advantage
      of the presence of prof. Ferguson and, before travelling to Rome, the Region
      Lombardy IPASVI Colleges (Coordinamento dei Collegi IPASVI della regione
      Lombardia) invited her to talk on the same topic during a jointed Conference with
      CNAI at Circolo della Stampa of Milan on 23rd October. 

PMID- 24083501
TI  - Activation-induced deaminase-coupled DNA demethylation is not crucial for the
      generation of induced pluripotent stem cells.
AB  - DNA methylation constitutes a major obstacle in the reprogramming of cells to
      pluripotency. Although little is known regarding the molecular mechanisms of DNA
      demethylation, activation-induced deaminase (AID), which is known to function in
      antibody diversification, has been implicated in DNA demethylation through a base
      excision repair (BER)-mediated pathway. Here we comprehensively examine the
      plausibility of coupled AID-BER demethylation in the generation of induced
      pluripotent stem cells (iPSCs) and show that AID is dispensable for reprogramming
      cells into iPSCs. Additionally, the overexpression of AID and other factors
      involved in AID-coupled DNA demethylation does not increase the efficiency of
      reprogramming. Moreover, BER is not likely to play a role in this process. Our
      results indicate that the reactivation of key genes governing the pluripotency
      circuitry occurs through a mechanism that is independent of deamination-coupled
      demethylation. 

PMID- 24083503
TI  - Multikinase inhibitors for treating high-risk myelodysplastic syndromes: can this
      be brought into clinical practice?

PMID- 24083502
TI  - Clustering of lifestyle risk factors and poor physical function in older adults:
      the Hertfordshire cohort study.
AB  - OBJECTIVES: To examine the relationship between number of lifestyle risk factors
      (out of low physical activity, poor diet, obesity, smoking) and physical function
      in older community-dwelling men and women. DESIGN: Cross-sectional study,
      Hertfordshire, United Kingdom. PARTICIPANTS: Men (n = 1,682) and women (n =
      1,540) aged 59 to 73. MEASUREMENTS: Physical activity was assessed using an
      administered questionnaire with a score from 0 to 100; low activity was defined
      as a score of 50 or less. Diet was assessed using a food frequency questionnaire;
      diet quality was assessed according to a score for a principal component analysis
      defined "healthy" dietary pattern. Poor diet was categorized as a dietary pattern
      score in the lowest quarter of the distribution. Obesity was defined as a body
      mass index of 30.0 kg/m(2) or more. Physical function was assessed according to
      self-report (SF-36); poor function was defined as a score in lowest quarter of
      the distribution. A subgroup of participants had objective assessments of
      physical function (Timed Up-and-Go Test, timed 3-m walk, chair rises, one-legged
      standing balance). RESULTS: There was a graded increase in prevalence of poor
      self-reported physical function in men and women with increasing number of risk
      factors (men, adjusted odds ratio (AOR) for 3 or 4 risk factors vs none = 3.79,
      95% confidence interval (CI) = 2.31-6.21; women, AOR = 5.37, 95% CI = 2.66
      10.84). With the exception of balance, the objective assessments also showed
      graded relationships with number of risk factors, such that more risk factors was
      associated with poorer physical function. CONCLUSION: These modifiable lifestyle
      risk factors are linked to marked differences in risk of poorer physical function
      in older adults. Efforts to encourage healthy lifestyles have the potential to
      improve physical function and to promote healthier ageing.

PMID- 24083504
TI  - Chromosomal variation in the tropical armoured catfish Callichthys callichthys
      (Siluriformes, Callichthyidae): implications for conservation and taxonomy in a
      species complex from a Brazilian hotspot.
AB  - The Neotropical catfish family Callichthyidae is characterized by wide karyotype
      variation, although reports are restricted to a few species/populations. This
      work provides new chromosomal information in two populations of armoured catfish
      (Callichthys callichthys) within the Atlantic forest boundaries in northeastern
      Brazil. Both populations of C. callichthys presented 2n=54 (16 metacentric, 24
      submetacentric, 6 subtelocentric, and 8 acrocentric chromosomes) with occurrence
      of a metacentric B macrochromosome, reported for the first time in "2n=54"
      karyomorph. The lack of heterochromatin in the supernumerary chromosome suggests
      a recent origin of Bs with a significant difference in their frequency (p<0.05)
      between localities. Contrasting to the predominance of single nucleolus organizer
      regions (NORs) in other populations from South America, a remarkable polymorphism
      of 18S rDNA and GC-rich sites was detected, inasmuch as NOR phenotypes were
      unique for each individual, comprising up to 13 NOR-bearing chromosomes. The 5S
      rDNA was also mapped onto multiple chromosomes nonsyntenic to NORs. Such
      divergence in a number of NORs and occurrence of an euchromatic B chromosome in
      relation to other karyomorphs reinforces the divergent evolution of C.
      callichthys populations. Furthermore, these results also support central and
      drier Atlantic forest areas in northeastern Brazil as a biodiversity hotspot.

PMID- 24083507
TI  - Effect of water on structural and frictional properties of self assembled
      monolayers.
AB  - Self-assembled monolayers (SAMs) of n-alkanethiols [(CH3(CH2)(n-1), n = 14, 15]
      on Au(111) in the presence of water have been simulated by molecular dynamics
      simulation. The behavior and effects of compression on structural characteristics
      and water penetration into monolayers under different ranges of normal pressures
      have been investigated. Frictional properties of hydrated SAM systems under
      various sliding velocities, and loading conditions are examined to explore
      correlation between the amount of water penetration and friction. Simulations for
      one odd and one even SAM (C14 and C15) systems have revealed interesting odd-even
      effects in water penetration and frictional properties. We have also compared the
      frictional and structural properties of hydrated systems to that of dry SAM-Au
      (one surface of gold is covered by SAM) and SAM-SAM (both gold substrates are
      covered by SAM) contacts. The results reveal that the even hydrated SAM (C14)
      shows lower friction coefficient compared with the odd hydrated SAM (C15). We
      found the presence of water reduces the friction only at lower pressures; and at
      higher pressures, dry SAM-Au contacts offer lower friction. It was interesting to
      see that the lubricity effect of water was much stronger for the odd system and
      persisted to slightly higher pressures (300 MPa for the even SAM and 700 MPa for
      the odd SAM). At higher pressures, for both odd and even systems, the presence of
      water increased the friction. We also found that at low sliding velocities and
      higher pressures apparent water viscosity was enhanced by up to 3 orders of
      magnitude, indicating possible solidification.

PMID- 24083506
TI  - Transmission potential of influenza A/H7N9, February to May 2013, China.
AB  - BACKGROUND: On 31 March 2013, the first human infections with the novel influenza
      A/H7N9 virus were reported in Eastern China. The outbreak expanded rapidly in
      geographic scope and size, with a total of 132 laboratory-confirmed cases
      reported by 3 June 2013, in 10 Chinese provinces and Taiwan. The incidence of
      A/H7N9 cases has stalled in recent weeks, presumably as a consequence of live
      bird market closures in the most heavily affected areas. Here we compare the
      transmission potential of influenza A/H7N9 with that of other emerging pathogens
      and evaluate the impact of intervention measures in an effort to guide pandemic
      preparedness. METHODS: We used a Bayesian approach combined with a SEIR
      (Susceptible-Exposed-Infectious-Removed) transmission model fitted to daily case
      data to assess the reproduction number (R) of A/H7N9 by province and to evaluate
      the impact of live bird market closures in April and May 2013. Simulation studies
      helped quantify the performance of our approach in the context of an emerging
      pathogen, where human-to-human transmission is limited and most cases arise from
      spillover events. We also used alternative approaches to estimate R based on
      individual-level information on prior exposure and compared the transmission
      potential of influenza A/H7N9 with that of other recent zoonoses. RESULTS:
      Estimates of R for the A/H7N9 outbreak were below the epidemic threshold required
      for sustained human-to-human transmission and remained near 0.1 throughout the
      study period, with broad 95% credible intervals by the Bayesian method (0.01 to
      0.49). The Bayesian estimation approach was dominated by the prior distribution,
      however, due to relatively little information contained in the case data. We
      observe a statistically significant deceleration in growth rate after 6 April
      2013, which is consistent with a reduction in A/H7N9 transmission associated with
      the preemptive closure of live bird markets. Although confidence intervals are
      broad, the estimated transmission potential of A/H7N9 appears lower than that of
      recent zoonotic threats, including avian influenza A/H5N1, swine influenza H3N2sw
      and Nipah virus. CONCLUSION: Although uncertainty remains high in R estimates for
      H7N9 due to limited epidemiological information, all available evidence points to
      a low transmission potential. Continued monitoring of the transmission potential
      of A/H7N9 is critical in the coming months as intervention measures may be
      relaxed and seasonal factors could promote disease transmission in colder months.

PMID- 24083505
TI  - Lipid-coated Cisplatin nanoparticles induce neighboring effect and exhibit
      enhanced anticancer efficacy.
AB  - Encapsulation of cisplatin (CDDP) into nanoparticles (NPs) with high drug loading
      and encapsulation efficiency has been difficult due to the poor solubility of
      CDDP. However, this barrier has been overcome with a reverse microemulsion method
      appropriating CDDP's poor solubility to our advantage promoting the synthesis of
      a pure cisplatin nanoparticle with a high drug loading capacity (approximately
      80.8 wt %). Actively targeted CDDP NPs exhibited significant accumulation in
      human A375M melanoma tumor cells in vivo. In addition, CDDP NPs achieved potent
      antitumor efficacy through the neighboring effect at a dose of 1 mg/kg when
      injected weekly via iv without inducing nephrotoxicity. The neighboring effect
      regards an observation made in vivo when the tumor cells that took up CDDP NPs
      released active drug following apoptosis. Via diffusion, surrounding cells that
      were previously unaffected showed intake of the released drug and their apoptosis
      soon followed. This observation was also made in vitro when A375M melanoma tumor
      cells incubated with CDDP NPs exhibited release of active drug and induced
      apoptosis on untreated neighboring cells. However, the neighboring effect was
      unique to rapidly proliferating tumor cells. Liver functional parameters and H&E
      staining of liver tissue in vivo failed to detect any difference between CDDP NP
      treated and control groups in terms of tissue health. By simultaneously promoting
      an increase in cytotoxicity and a lesser degree of side effects over free CDDP,
      CDDP NPs show great therapeutic potential with lower doses of drug while
      enhancing anticancer effectiveness. 

PMID- 24083508
TI  - A man with small vessel vasculitis presenting with brachial diplegia, multiple
      cranial mononeuropathies and severe orthostatic hypotension in diabetes mellitus:
      a case report.
AB  - INTRODUCTION: We report a rare case of fulminant vasculitic mononeuropathy
      resulting in brachial diplegia, with suspected brainstem and autonomic nervous
      system involvement in a patient with diabetes mellitus. CASE PRESENTATION: A 58
      year-old Hispanic Caucasian man with diabetes mellitus presented with a 1-year
      history of progressive bilateral upper extremity weakness, orthostatic
      intolerance and progressive memory decline. Diagnostic evaluation including
      laboratory tests for progressive encephalopathies, systemic inflammatory and non
      inflammatory neuropathies, cerebrospinal fluid analyses, electrodiagnostic
      studies, and nerve biopsy were performed. Clinical examination revealed moderate
      cognitive deficits on the Montreal Cognitive Assessment scale, bilateral facial
      weakness and weakness of bilateral shoulder girdle and intrinsic hand muscles.
      Cerebrospinal fluid analyses revealed elevated protein and an elevated
      immunoglobulin G synthesis rate, suggesting an immune-mediated process. Further
      laboratory work up was non-diagnostic. Electrodiagnostic studies demonstrated
      chronic asymmetric axonal mononeuropathies with ongoing denervation. A
      superficial radial nerve biopsy showed a chronic vasculitic neuropathy.
      Glucocorticosteroid treatment, symptomatic pharmacologic and supportive non
      pharmacologic therapies resulted in improved clinical outcomes despite challenges
      with glycemic control. CONCLUSIONS: This case report emphasizes the importance of
      a thorough evaluation of atypical or uncommon neuromuscular presentations in
      diabetic patients without etiological presumptions. This is necessary in order to
      promptly establish a diagnosis, initiate appropriate therapies and prevent
      irreversible nerve injury.

PMID- 24083509
TI  - Metabolomic analysis and differential expression of anthocyanin biosynthetic
      genes in white- and red-flowered buckwheat cultivars (Fagopyrum esculentum).
AB  - Red-flowered buckwheat ( Fagopyrum esculentum ) is used in the production of tea,
      juice, and alcohols after the detoxification of fagopyrin. In order to
      investigate the metabolomics and regulatory of anthocyanin production in red
      flowered (Gan-Chao) and white-flowered (Tanno) buckwheat cultivars, quantitative
      real-time RT-PCR (qRT-PCR), gas chromatography time-of-flight mass spectrometry
      (GC-TOFMS), and high performance liquid chromatography (HPLC) were conducted. The
      transcriptions of FePAL, FeC4H, Fe4CL1, FeF3H, FeANS, and FeDFR increased
      gradually from flowering stage 1 and reached their highest peaks at flowering
      stage 3 in Gan-Chao flower. In total 44 metabolites, 18 amino acids, 15 organic
      acids, 7 sugars, 3 sugar alcohols, and 1 amine were detected in Gan-Chao flowers.
      Two anthocyanins, cyanidin 3-O-glucoside and cyanidin 3-O-rutinoside, were
      identified in Gan-Chao cultivar. The first component of the partial least-squares
      to latent structures-discriminate analysis (PLS-DA) indicated that high amounts
      of phenolic, shikimic, and pyruvic acids were present in Gan-Chao. We suggest
      that transcriptions of genes involved in anthocyanin biosynthesis, anthocyanin
      contents, and metabolites have correlation in the red-flowered buckwheat Gan-Chao
      flowers. Our results may be helpful to understand anthocyanin biosynthesis in red
      flowered buckwheat. 

PMID- 24083510
TI  - Shotgun protein profile of human adipose tissue and its changes in relation to
      systemic amyloidoses.
AB  - In systemic amyloidosis, accumulation of misfolded proteins as extracellular
      amyloid fibrils in tissues causes severe organ dysfunction, but the molecular
      events of tissue damage related to amyloid deposition are still largely unknown.
      Through the use of the MudPIT proteomic approach, comprehensive protein profiles
      of human amyloid-affected adipose tissue from patients and its control (non
      amyloid-affected) counterpart were acquired. Label-free comparison between
      patients and controls made it possible to highlight differences related to the
      presence of amyloid, by describing up- and down-represented proteins, connected
      into interacting networks. In particular, extracellular matrix (ECM), protein
      folding, lipid metabolism, and mitochondrial functions were among the most
      affected structural/functional pathways. The reported results, obtained with no a
      priori hypotheses, represent a significant step forward in the clarification of
      the molecular mechanisms involved in amyloidoses at tissue level and are the
      premise for understanding protein misfolding diseases. 

PMID- 24083511
TI  - Growth-Inhibiting and morphostructural effects of constituents identified in
      Asarum heterotropoides root on human intestinal bacteria.
AB  - BACKGROUND: The growth-inhibiting and morphostructural effects of seven
      constituents identified in Asarum heterotropoides root on 14 intestinal bacteria
      were compared with those of the fluoroquinolone antibiotic ciprofloxacin. METHOD:
      A microtiter plate-based bioassay in sterile 96-well plates was used to evaluate
      the minimal inhibitory concentrations (MICs) of the test materials against the
      organisms. RESULTS: delta-3-Carene (5) exhibited the most potent growth
      inhibition of Gram-positive bacteria (Clostridium difficile ATCC 9689,
      Clostridium paraputrificum ATCC 25780, Clostridium perfringens ATCC 13124, and
      Staphylococcus aureus ATCC 12600) and Gram-negative bacteria (Escherichia coli
      ATCC 11775 and Bacteroides fragilis ATCC 25285) (minimal inhibitory
      concentrations (MIC), 0.18-0.70 mg/mL) except for Salmonella enterica serovar
      Typhimurium ATCC 13311 (MIC, 2.94 mg/mL). The MIC of methyleugenol (2), 1,8
      cineole (3), alpha-asarone (4), (-)-asarinin (6), and pellitorine (7) was between
      1.47 and 2.94 mg/mL against all test bacteria (except for compound 2 against C.
      difficile (0.70 mg/mL); compounds 1 (23.50 mg/mL) and 4 (5.80 mg/mL) against C.
      paraputricum; compounds 2 (5.80 mg/mL), 4 (12.0 mg/mL), and 7 (0.70 mg/mL)
      against C. perfringens); compound 1 against E. coli (7.20 mg/mL) and S. enterica
      serovar Typhimurium (12.0 mg/mL). Overall, all of the constituents were less
      potent at inhibiting microbial growth than ciprofloxacin (MIC, 0.063-0.25 mg/
      mL). The lactic acid-producing bacteria (four bifidobacteria and two
      lactobacilli) and one acidulating bacterium Clostridium butyricum ATCC 25779 were
      less sensitive and more susceptible than the five harmful bacteria and two
      nonpathogenic bacteria (B. fragilis and E. coli) to the constituents and to
      ciprofloxacin, respectively. Beneficial Gram-positive bacteria and harmful and
      nonpathogenic Gram-negative bacteria were observed to have different degrees of
      antimicrobial susceptibility to the constituents, although the antimicrobial
      susceptibility of the harmful Gram-positive bacteria and the harmful and
      nonpathogenic Gram-negative bacteria was not observed. Scanning electron
      microscopy observations showed different degrees of physical damage and
      morphological alteration to both Gram-positive and Gram-negative bacteria treated
      with alpha-asarone, delta-3-carene, pellitorine, or ciprofloxacin, indicating
      that they do not share a common mode of action. CONCLUSION: A. heterotropoides
      root-derived materials described merit further study as potential antibacterial
      products or lead molecules for the prevention or eradication from humans from
      diseases caused by harmful intestinal bacteria.

PMID- 24083512
TI  - Attention please: evaluative priming effects in a valent/non-valent
      categorisation task (reply to Werner & Rothermund, 2013).
AB  - It has previously been argued (a) that automatic evaluative stimulus processing
      is dependent upon feature-specific attention allocation (FSAA) and (b) that
      evaluative priming effects can arise in the absence of dimensional overlap
      between the prime set and the response set. In opposition to these claims, Werner
      and Rothermund (2013) recently reported that they were unable to replicate the
      evaluative priming effect in a valent/non-valent categorisation task. In this
      manuscript, I report the results of a conceptual replication of the studies by
      Werner and Rothermund (2013). A clear-cut evaluative priming effect was found,
      thus supporting the initial claims about FSAA and dimensional overlap. An
      explanation for these divergent findings is discussed.

PMID- 24083513
TI  - Liposomes with double-stranded DNA anchoring the bilayer to a hydrogel core.
AB  - Liposomes are important biomolecular nanostructures for handling membrane
      associated molecules in the lab and delivering drugs in the clinic. In addition
      to their biomedical applications, they have been widely used as model cell
      membranes in biophysical studies. Here we present a liposome-based model membrane
      that mimics the attachment of membrane-resident molecules to the cytoskeleton. To
      facilitate this attachment, we have developed a lipid-based hybrid nanostructure
      in which the liposome bilayer membrane is covalently anchored to a biocompatible
      poly(ethylene) glycol (PEG) hydrogel core using short double-stranded DNA (dsDNA)
      linkers. The dsDNA linkers connect cholesterol groups that reside in the bilayer
      to vinyl groups that are incorporated in the cross-linked hydrogel backbone. Size
      exclusion chromatography (SEC) of intact and surfactant-treated nanoparticles
      confirms the formation of anchored hydrogel structures. Transmission electron
      microscopy (TEM) shows ~100 nm nanoparticles even after removal of unanchored
      phospholipids. The location of dsDNA groups at the hydrogel-bilayer interface is
      confirmed with a fluorescence assay. Using DNA as a linker between the bilayer
      and a hydrogel core allows for temperature-dependent release of the anchoring
      interaction, produces polymer nanogels with addressible hybridization sites on
      their surface, and provides a prototype structure for potential future
      oligonucleotide drug delivery applications.

PMID- 24083514
TI  - Wild foods from farm and forest in the East Usambara Mountains, Tanzania.
AB  - This study explored the role of wild foods in the diets of children and mothers
      in the East Usambara Mountains (N = 274 dyads). We identified 92 wild food
      species. Although dietary diversity (most measures) was not different between
      seasons, wild foods accounted for a greater percentage of items consumed in the
      wet (food insecure) season. Many wild foods were obtained on farm; wild foods
      obtained from the forest accounted for less than 3% of food items consumed. Wild
      foods were used by virtually all informants but contributed only 2% of total
      energy in the diet. However, they contributed large percentages of vitamin A
      (RAE) (31%), vitamin C (20%), and iron (19.19%). Agricultural factors (e.g.,
      hours spent in farm) were associated with greater wild food use. These findings
      suggest participation in agriculture may be important for the maintenance of wild
      food use, and that wild foods can play an important role in the nutritional
      resilience of local people. 

PMID- 24083515
TI  - "We never ate like that, not fast food, or junk foods": accounts of changing
      maternal diet in a tourist community in rural Costa Rica.
AB  - This investigation examines maternal diet in rural Costa Rica in the context of
      recent political economic changes. Results show that increased availability of
      non-local food items, (i.e., pizza and processed foods) has influenced maternal
      dietary choices. Information pathways, which have traditionally provided women
      with knowledge about maternal diet from family members, are also shifting.
      Younger women turn to the local clinic and the media for information about
      maternal diet, and traditional practices, such as cuarentena (40-day postpartum
      period), are no longer being observed. Changing practices may be linked with
      shifting information pathways, as well as self-reported weight gain among women. 

PMID- 24083516
TI  - Determinants of edible oil choice by households in Tamil Nadu, India.
AB  - This study investigated the major determinants that influence the choice of
      edible oils by households across geographical zones in Tamil Nadu state, India.
      The primary data from 1,000 sample households were collected using a structured
      pre-tested questionnaire. Multinomial logit model was fitted for determining the
      factors. The results revealed that education, income, and households with a
      history of health problems were the important determinants that influenced the
      choice of low-saturated-fat oils, whereas the larger size households and weaker
      section households preferred low-priced palm oil. Income and education levels in
      Tamil Nadu state surged ahead in recent years. In consonance to these changes the
      nontraditional low-saturated fat containing sunflower oil demand will increase in
      many folds in coming years. Hence, besides traditional oils, sunflower oil
      production has to be stepped up on "mission mode" through appropriate production
      programs to meet the present and future edible oil demand domestically. 

PMID- 24083517
TI  - Making sense of agrobiodiversity, diet, and intensification of smallholder family
      farming in the Highland Andes of Ecuador.
AB  - Methods are needed for helping researchers and farmers to interactively describe
      and analyze local practices in search of opportunities for improving health,
      environment, and economy. The authors worked with smallholder family farmers in
      five Andean villages in Ecuador to apply participatory four-cell analysis (PFCA)
      in characterizing agrobiodiversity. Margelef and Shannon indices examined
      ecological richness and evenness, and a simplified 24-hour dietary recall
      characterized food consumption. Cross-analysis tested interactions among
      agrobiodiversity, farm size, and diet. Overall trends appeared to work against
      sustainable intensification, with notable heterogeneity and positive deviance
      found in the practices of relatively smaller enterprises, representing a
      potential resource for sustainable intensification. The suite of methods was
      determined useful for initiating researcher-farmer explorations of promising
      innovation pathways. 

PMID- 24083520
TI  - Local strain engineering in atomically thin MoS2.
AB  - Controlling the bandstructure through local-strain engineering is an exciting
      avenue for tailoring optoelectronic properties of materials at the nanoscale.
      Atomically thin materials are particularly well-suited for this purpose because
      they can withstand extreme nonhomogeneous deformations before rupture. Here, we
      study the effect of large localized strain in the electronic bandstructure of
      atomically thin MoS2. Using photoluminescence imaging, we observe a strain
      induced reduction of the direct bandgap and funneling of photogenerated excitons
      toward regions of higher strain. To understand these results, we develop a
      nonuniform tight-binding model to calculate the electronic properties of MoS2
      nanolayers with complex and realistic local strain geometries, finding good
      agreement with our experimental results. 

PMID- 24083519
TI  - Structured sedation programs in the emergency department, hospital and other
      acute settings: protocol for systematic review of effects and events.
AB  - BACKGROUND: The use of procedural sedation outside the operating theatre has
      increased in hospital settings and has gained popularity among non
      anesthesiologists. Sedative agents used for procedural pain, although effective,
      also pose significant risks to the patient if used incorrectly. There is
      currently no universally accepted program of education for practitioners using or
      introducing procedural sedation into their practice. There is emerging literature
      identifying structured procedural sedation programs (PSPs) as a method of
      ensuring a standardized level of competency among staff and reducing risks to the
      patient. We hypothesize that programs of education for healthcare professionals
      using procedural sedation outside the operating theatre are beneficial in
      improving patient care, safety, practitioner competence and reducing adverse
      event rates. METHODS/DESIGN: Electronic databases will be systematically searched
      for studies (randomized and non-randomized) examining the effectiveness of
      structured PSPs from 1966 to present. Database searches will be supplemented by
      contact with experts, reference and citation checking, and a grey literature
      search. No language restriction will be imposed. Screening of titles and
      abstracts, and data extraction will be performed by two independent reviewers.
      All disagreements will be resolved by discussion with an independent third party.
      Data analysis will be completed adhering to procedures outlined in the Cochrane
      Handbook of Systematic Reviews of Interventions. If the data allows, a meta
      analysis will be performed. DISCUSSION: This review will cohere evidence on the
      effectiveness of structured PSPs on sedation events and patient outcomes within
      the hospital and other acute care settings. In addition, it will examine key
      components identified within a PSP associated with patient safety and improved
      patient outcomes. TRIAL REGISTRATION: PROSPERO registration number:
      CRD42013003851.

PMID- 24083521
TI  - Disappearing lakes in semiarid Northern China: drivers and environmental impact.
AB  - The widely distributed 241 lakes in the semiarid region of China bordering the
      Asian Gobi desert provide an irreplaceable environment for the region's human
      inhabitants, livestock, and wildlife. Using satellite imagery, we tracked the
      changing areas of lake water and freshwater/salty marshes during the last four
      decades and correlated observed changes with concurrent temperature and
      precipitation. On average, most of the lake size groups across different
      subregions showed a reduction in area from the 1970s to 2000s, particularly from
      the 1990s to 2000s (P < 0.05); 121 of the 241 lakes became fully desiccated at
      the end of the 2000s. Our results confirmed the prevalence of drought-induced
      lake shrinkage and desiccation at a regional scale, which has been sustained
      since the year 2000, and highlighted an accelerated shrinkage of individual lakes
      by human water use in the agriculture-dominated regions. Lake waters have become
      salinized, and freshwater marsh has been replaced by salty marsh, threatening the
      populations of endangered waterfowl species such as the red-crowned crane as well
      as the aquatic ecosystem. Although the dry lakebeds are a potential source of
      dust, the establishment of salty marsh on bare lake beds could have partially
      reduced dust release due to the increase in vegetation cover. 

PMID- 24083522
TI  - Promising results after single-stage reconstruction of the nipple and areola
      complex.
AB  - INTRODUCTION: Reconstruction of the nipple-areola complex (NAC) traditionally
      marks the end of breast reconstruction. Several different surgical techniques
      have been described, but most are staged procedures. This paper describes a
      simple single-stage approach. MATERIAL AND METHODS: We used a technique based on
      a local flap for reconstruction of the nipple in combination with immediate
      intradermal tattooing for reconstruction of the areola. RESULTS: We reviewed the
      outcome of 22 cases of women who had simple single-stage reconstruction over a
      period of one year. We found no major and only two minor complications including
      one case of partial flap necrosis and one case of infection. Only three patients
      needed additional tattooing after a three-month period. The cosmetic outcome was
      satisfactory and none of the patients needed corrective procedures. The mean
      procedure time for unilateral reconstruction was 43 min. (30-50 min.).
      CONCLUSION: This simple single-stage NAC reconstruction seems beneficial for both
      patient and surgeon as it seems to be associated with faster reconstruction and
      reduced procedure-related time without compromising the aesthetic outcome or the
      morbidity associated with surgery.

PMID- 24083523
TI  - Prevalence of diabetes mellitus in patients with shoulder symptoms is low.
AB  - INTRODUCTION: Patients with diabetes mellitus have a high risk of developing
      symptoms from their shoulder. The generally accepted theory is that high blood
      glucose levels cause excessive glycosylation and that the delay in diagnosing
      diabetes mellitus may influence the risk of acquiring a musculoskeletal disorder.
      The aim of the study was to determine whether there was a large percentage of
      undiagnosed diabetes mellitus in a population of patients with shoulder symptoms.
      MATERIAL AND METHODS: The study population consisted of patients who were
      referred by their GP with shoulder symptoms. HbA1c level was measured, and
      height, weight, sex, age and diabetes status were registered. Patients with
      shoulder symptoms were compared to a group of patients who had been referred with
      knee symptoms and to the regional prevalence of unknown and diagnosed diabetes
      mellitus. RESULTS: A total of 221 patients with shoulder symptoms were included.
      There was no significant difference in the prevalence of unknown diabetes
      mellitus between the group of patients with shoulder symptoms and the group of
      patients with knee symptoms or the regional prevalence. There was a significantly
      higher prevalence of diagnosed diabetes mellitus in the group of patients with
      shoulder symptoms. CONCLUSION: The low prevalence of unknown diabetes mellitus we
      observed in this study may be owed to the fact that upper extremity disorder
      often occurs years after onset of diabetes, and for that reason patients have
      already been diagnosed when the extremity disorder is present. This study
      demonstrates a higher prevalence of diagnosed diabetes mellitus among patients
      with shoulder symptoms. It is important for physicians to be aware of this in the
      treatment of patients with shoulder symptoms.

PMID- 24083524
TI  - High agreement between the Danish Ventral Hernia Database and hospital files.
AB  - INTRODUCTION: Ventral hernia repairs are common surgical procedures and quality
      monitoring with a high validity is mandatory. The aim of the present study was to
      validate the data quality of the Danish Ventral Hernia Database (DVHD). MATERIAL
      AND METHODS: All ventral hernia repairs performed in the Region of Zealand and
      registered in the DVHD between 1 October 2010 and 1 October 2011 were included.
      Eleven clinically relevant surgical variables in the DVHD were compared for
      agreement with data in hospital files. RESULTS: The Region of Zealand cohort
      included 410 ventral hernia repairs corresponding to 13.8% of the repairs
      registered in the DVHD in Denmark during the inclusion period. There was 89-99%
      agreement between data in the DVHD and hospital files (kappa = 0.75-0.99).
      CONCLUSION: The present study based on a regional cohort suggests that the DVHD
      can be used as a reliable tool to monitor clinical quality following ventral
      hernia repair.

PMID- 24083525
TI  - Staff attitudes towards patients with schizophrenia.
AB  - INTRODUCTION: Stigmatizing attitudes have been reported in international studies
      among staff in psychiatry. The authors wanted to investigate if this was the case
      in Denmark. MATERIAL AND METHODS: A survey of attitudes among staff at two
      psychiatric units in Copenhagen was performed using the Mental Illness:
      Clinicians' Attitudes scales. The scales have 16 questions to which another four
      questions were added by the authors. RESULTS: A total of 548 staff members
      answered the questions (61 doctors and 487 other professionals). The majority of
      the respondents believed in the possibility of recovery for patients and only a
      minority associated a high degree of dangerousness with schizophrenia. The cause
      of the illness was mainly regarded as being biological, but all agreed to a bio
      psycho-social aetiological approach. The majority of the respondents believed
      that the illness was chronic and agreed on the need for staff to also be aware of
      patients' somatic illness. The doctors did not question their role as "real
      doctors" or the scientific basis for psychiatry. The majority would not mind
      working with a colleague with schizophrenia, but about half would hesitate to
      disclose if they themselves were diagnosed with the illness. Being a woman
      working in community psychiatry with long experience and participation in a
      recovery educational programme was associated with less stigmatizing attitudes.
      CONCLUSION: The survey showed a relatively low level of stigmatizing attitudes.
      This runs counter to the results from international investigation. This trend
      could be interpreted both as a result of a shift towards a more recovery-oriented
      approach to treatment as well as a reflection of political correctness.

PMID- 24083526
TI  - Completeness and data validity for the Danish Fracture Database.
AB  - INTRODUCTION: Fracture-related surgery is among the most common orthopaedic
      procedures. However, to our knowledge, register-based quality assessment of
      fracture-related surgery has not previously been conducted. The Danish Fracture
      Database (DFDB) has been developed for the purpose of web-based quality
      assessment, but its properties as a valid data source have not previously been
      explored. We therefore investigated: 1) the completeness of data in the DFDB, and
      2) if the entered data are valid data sources for future quality assessment.
      MATERIAL AND METHODS: We have developed the internet-based DFDB in which data
      entry is performed by the surgeon. Data collection includes primary fracture
      surgery and reoperations. After full implementation of the database at two
      orthopaedic departments, we assessed the completeness and validity of the entered
      data for 322 patients operated during a one-month period. Validity was calculated
      as observed agreement. RESULTS: We recorded 83% completeness for all types of
      data entry, with 88% completeness for primary fracture surgery and 77% for
      reoperations, respectively. Patient- and trauma-related data were 82-100% valid.
      Surgery-related data included method of osteosynthesis and was valid in 89-99% of
      the cases. CONCLUSION: The DFDB is an easy to use web-based database for
      registration of fracture-related surgery. Shortly after its implementation, we
      recorded satisfactory completeness and high data validity, which makes the DFDB a
      valuable tool with potential for nationwide quality assessment of fracture
      related surgery.

PMID- 24083527
TI  - Patients highly value routine follow-up of skin cancer and cutaneous melanoma.
AB  - INTRODUCTION: Skin cancer follow-up is a substantial burden to outpatient
      clinics. Few studies have investigated patients' views on skin cancer follow-up
      and cutaneous melanoma. The objective was to investigate patients' perceived
      benefits and the impact of follow-up. MATERIAL AND METHODS: This study included
      an open sample of patients attending routine follow-up at the outpatient
      Departments of Plastic Surgery and Dermatology, Roskilde Hospital. A total of 218
      follow-up patients diagnosed with cutaneous malignant melanoma (MM), non-melanoma
      skin cancer (NMSC) or actinic keratosis (AK) completed a structured interview.
      RESULTS: A total of 97% patients found follow-up useful. Continuity and
      consistency were important. One third of patients felt some degree of pre follow
      up anxiety. The number of anxious MM patients was significantly greater than that
      of NMSC patients. No significant difference was found between the number of
      anxious MM and AK patients. Female gender, cohabitation and age younger than 50
      years were associated with increased levels of anxiety. No relation was found
      between the number of anxious patients or the level of anxiety and the duration
      of the follow-up period. CONCLUSION: The majority of patients who attended found
      that the follow-up had been useful. Certain demographic characteristics were
      associated with higher levels of anxiety and may be addressed by supportive
      efforts targeting these groups.

PMID- 24083528
TI  - Validation of the Danish version of the Oxford Elbow Score.
AB  - INTRODUCTION: The Oxford Elbow Score (OES) is a patient-related outcome measure
      quantifying quality of life in relation to elbow disorders. This 12-item patient
      administered English questionnaire comprises three domains: function, social
      psychological status and pain. The purpose of this study was to examine the
      structure and reliability of the Danish version of the OES (D-OES). MATERIAL AND
      METHODS: A total of 130 patients who had total elbow arthroplasty (TEA) surgery
      performed in the period from 1981 to 2008 completed the D-OES. The Disability of
      the Arm, Shoulder and Hand score (DASH) and the Mayo Elbow Performance Score
      (MEPS) were also completed with a view to examining the convergent validity of
      the D-OES. In 45 cases, the questionnaire was completed twice to allow for
      calculation of test-retest reliability. The structure of the questionnaire was
      tested using Rasch analysis. RESULTS: Overall internal consistency tested by
      Cronbach's alpha was 0.99. The test-retest reliability correlation coefficient
      was 0.99. Expressed in terms of Pearson's correlation coefficient, the convergent
      validity of the D-OES's functional, social-psychological and pain domain was
      0.78, 0.80 and 0.81, respectively, for the MEPS and -0.66, -0.58 and -0.49,
      respectively, for the DASH. The 12 items of the D-OES fitted the Rasch model, and
      the multidimensionality of the OES was confirmed. CONCLUSION: The Danish 12-item
      OES is a valid and reliable-patient administered questionnaire that can be used
      to quantify quality of life in patients with TEA.

PMID- 24083529
TI  - Bronchoschopy should always be performed in children on suspicion of foreign body
      aspiration.
AB  - INTRODUCTION: Foreign body aspiration (FBA) can have a fatal outcome, and the
      diagnosis is challenging since symptoms and signs may vary. We therefore
      investigated whether it was possible to identify predictors indicating the
      presence of a foreign body. MATERIAL AND METHODS: The medical records of children
      undergoing bronchoscopy at Odense University Hospital for suspected FBA in the
      period from 1977 to 2010 were reviewed and analyzed. RESULTS: A total of 143
      children underwent bronchoscopy due to suspected FBA. The medical records of 137
      of these children were accessible. Their median age was 1.84 years, 62.8% were
      male and foreign bodies were found in 76 cases (55.5%). The only variable that
      statistically significantly predicted the presence of a foreign body was a
      radiologic finding (any abnormal chest X-ray or fluoroscopy) (p = 0.023). A
      foreign body was found in 22 out of 47 (46.8%) patients with no radiologic
      findings and in three of 11 (27%) patients with neither symptoms at admission nor
      radiologic or physical findings. CONCLUSION: Parental suspicion of an FBA
      indicates acute bronchoscopy in children regardless of signs, symptoms and
      findings.

PMID- 24083530
TI  - Retinal angiographic blood flowmetry is reduced in the ocular ischaemic syndrome.
AB  - INTRODUCTION: The aim of this study was to examine the use of quantitative
      fluorescein angiographic analysis as a means of estimating rates of perfusion of
      the retina in eyes with a circulatory deficit secondary to carotid artery
      stenosis. MATERIAL AND METHODS: The study included 21 eyes with ocular ischaemic
      syndrome (OIS) and 20 control eyes from subjects with carotid artery stenosis but
      without signs of ocular ischaemia. Analyses of video fluorescein angiograms
      extracting time intervals for the time delay between specific phases of the
      angiogram were performed. Time delay was compared between groups and in relation
      to degree of carotid artery stenosis and ocular systolic blood pressure. RESULTS:
      Among the three flow indices of retinal perfusion (arteriovenous passage time 1
      (AVP1), arteriovenous passage time 2 (AVP2) and venous filling time (VP)), those
      including the venous filling phase were significantly prolonged in the OIS group.
      Furthermore, AVP2 was delayed by 3 sec. in OIS eyes (16.6 sec. versus 13.6 sec.
      in controls). VP was 2.4 sec. longer in OIS eyes (11.5 sec. versus 9.1 sec.). We
      found a significant correlation between AVP2 and ocular perfusion pressure, but
      no correlation between the degree of carotid artery stenosis and any of the flow
      indices. CONCLUSION: In a patient population spanning a wide ocular systolic
      blood pressure range, angiography-based quantitative flowmetry demonstrated a
      difference between carotid artery stenosis patients with and without OIS and a
      correlation between flow and ocular perfusion pressure. While angiographic
      flowmetry proved effective in discriminating between groups of individuals, it
      can only be used to support the diagnosis of the ocular ischaemic syndrome in
      patients with extreme flow reduction.

PMID- 24083531
TI  - The new ICMJE recommendations.

PMID- 24083532
TI  - Need to combine individual strategies with population-level strategies in the
      prevention of coronary heart disease.
AB  - INTRODUCTION: The aim of this paper was to examine the relation between the
      distribution of risk, the distribution of coronary heart disease (CHD) events and
      the proportion who develop CHD according to risk. MATERIAL AND METHODS: Baseline
      data from a cross-sectional study conducted in 1999-2001 comprising information
      on systolic blood pressure, low density lipoprotein cholesterol and a multifactor
      risk score, The Copenhagen Risk Score, were related to ten years of fatal and non
      fatal events of CHD in 6,784 participants. RESULTS: The results were unambiguous
      regarding all three examined parameters. They showed that the majority of all
      fatal and non-fatal events of CHD occur within the large group of the population
      which is at low or no risk of CHD. DISCUSSION: The three determinants in relation
      to CHD events indicate that changing the risk of a whole population through
      widespread comprehensive societal policies may be more efficient than medical
      treatment and health counselling targeting persons already at high-risk, which
      will be of benefit for the individual persons only. FUNDING: Funding was received
      from The Health Insurance Foundation (grant number 2010 B 131). The funders had
      no role in study design, data collection and analysis, decision to publish, or
      preparation of the manuscript.

PMID- 24083533
TI  - Corpus callosum in aging and dementia.
AB  - The overarching objective of the thesis was to investigate the morphological
      changes in the corpus callosum (CC) in aging and dementia in relation to its role
      in cognitive and motor decline. The CC is the largest white matter tract in the
      brain, containing upwards of 200 million axons, and is believed important for
      communication and interaction between the two cerebral hemispheres. Historically,
      the role of white matter, including the CC, in relation to cognitive function has
      often been eclipsed by the predominance of the cortex, and led to a
      "corticocentric" view of the brain and cognitive function. However, from the
      1960s and onwards, the role of lesions in the white matter in the appearence of
      cognitive deficits and diseases such as dementia has become increasingly evident.
      Many studies have indicated that AD is associated with CC atrophy, but the
      precise pattern of subregional CC atrophy in different disease stages remains
      undetermined. In study I, we establish that atrophy is present primarily in the
      posterior CC early in AD, and that atrophy of the CC is associated with faster
      disease progression. This finding supports a model where posterior atrophy is the
      earliest changes in the CC in AD patients, with atrophy of anterior CC being a
      later pathological event. To further elucidate the role of CC atrophy in
      dementia, we examined a population of 329 elderly subjects, and found that a
      higher rate of tissue loss in posterior CC is associated with an increased risk
      of dementia. This study represents the first to examine CC in elderly subjects
      longitudinally. In the same cohort, we investigated whether impairment in
      specific cognitive domains was associated with CC tissue loss. Previous studies
      had shown that processing speed and executive functions may be particularly
      reliant on the CC. Our findings indicated that CC tissue loss leads to selective
      impairment of processing speed but not memory or executive function deficits.
      Finally, CC tissue loss was also associated with impairment of motor function.
      Overall, the present findings confirm and extend the role of the CC in dementia
      and age-associated cognitive and motor deficits. 

PMID- 24083534
TI  - Epidemiological, clinical and immunological aspects of neuromyelitis optica
      (NMO).
AB  - Neuromyelitis optica (NMO) is an inflammatory demyelinating disease (IDD) of the
      central nervous system (CNS) and probably the most common non-multiple sclerosis
      (MS) CNS IDD. Serum immunoglobulin G autoantibodies have been identified in the
      majority of NMO patients with the water channel aquaporin-4 (AQP4) as their main
      target autoantigen. Previous studies have suggested ethnicity-based prevalence
      differences of NMO. The genetic background for these putative differences is not
      known. An HLA-association with NMO has been identified, but the association is
      not very pronounced. Human and experimental studies support that anti-AQP4
      antibodies/NMO-IgG are involved in the pathogenesis of NMO. Previous experimental
      animal models have reported induction of NMO-like histopathology in animals by
      transfer of human anti-AQP4 antibodies/NMO-IgG. A main goal of this PhD thesis
      was to perform a population-based study in a predominantly Caucasian population
      (in the Region of Southern Denmark) to estimate the incidence and prevalence of
      NMO and describe the clinical phenotypes in this population. Furthermore the aims
      were to investigate whether autoimmunity underlies or contributes to the
      pathogenesis of NMO with specific clinical, immunogenetic and experimental
      perspectives. The yearly incidence rate of NMO in the population was estimated to
      be 0.4 per 105 person-years (95% CI 0.30-0.54) and the prevalence was 4.4 per 105
      (95% CI 3.1-5.7). The results indicated that NMO is more common in a Caucasian
      population than earlier believed. Clinical, radiologic and serological data were
      reviewed in order to establish the diagnostic accuracy of anti-AQP4
      antibodies/NMO-IgG for specific syndromes in NMO. We observed assay
      characteristics with a sensitivity of 62% and a specificity of 100%. The
      diagnosis of NMO based on either the Wingerchuk 2006 criteria or the United
      States National Multiple Sclerosis Society 2008 criteria could be made purely on
      clinical grounds in a high proportion (64%) of cases. Heterogeneity of clinical
      NMO manifestations including optic neuritis, longitudinal extensive transverse
      myelitis (LETM) and brain lesions were observed. In the clinical immunogenetic
      study we observed that NMO patients had frequent co-existence of autoimmune
      disease and family occurrence of NMO and MS. The frequency of HLA-DQB1*0402
      allele was increased in NMO and a significantly increased frequency of the PD
      1.3A allele in the NMO patients was observed. The data suggest a possible genetic
      autoimmune dependency of NMO. In the experimental part a novel animal model for
      NMO was established, utilizing the minimally invasive intrathecal route for
      antibody administration that does not involve blood brain barrier disruption or
      pre-existing CNS inflammation. Human IgG from AQP-4 antibody-positive NMO
      patients (from the clinical study) were injected together with human complement
      to study the effects on CNS. NMO-like histological lesions were observed at
      topographically restricted sites at the ependyma and in the parenchyma of the
      brainstem, cerebellum and periventricular areas. The lesions were characterized
      by deposition of immunoglobulin and complement, loss of AQP-4 expression and loss
      of reactive astrocytes co-localizing with inflammatory cell infiltration. This
      pattern is similar to the characteristic histological and radiologic features of
      human NMO lesions. Taken together this PhD combined clinical, epidemiological,
      neuroimaging, genetic and immunological data, which contribute to the
      characterization of the natural course of the disease and understanding of the
      pathogenesis of NMO. Practical consequences may be earlier diagnosis of NMO and
      better distinction of NMO from MS and other IDDs, important due to differences in
      prognosis and therapy. 

PMID- 24083535
TI  - Atrial fibrillation.
AB  - Atrial fibrillation (AF) is a common complication after myocardial infarction
      (MI) and new-onset AF has been demonstrated to be associated with adverse outcome
      and a large excess risk of death in both MI and aortic stenosis (AS) patients.
      Prevention of new-onset AF is therefore a potential therapeutic target in AS and
      MI patients. Lipid-lowering drugs, particularly statins, have anti-inflammatory
      and antioxidant properties that may prevent AF. Accordingly, statins are
      recommended as a class IIa recommendation for prevention of new-onset AF after
      coronary artery bypass grafting (CABG). However, this preventive effect has not
      been investigated on new-onset AF in asymptomatic patients with AS or a large
      scale first-time MI patient sample and data in patients not undergoing invasive
      cardiac interventions are limited. This PhD thesis was conducted at the Heart
      Centre, Rigshospitalet, Denmark, with the aim to investigate the three
      aforementioned questions and to add to the existing evidence of AF prevention
      with statins. This was done using three different settings: 1) a randomized
      patients sample of 1,873 from the Simvastatin and Ezetimibe in Aortic Stenosis
      (SEAS) study, 2) a register patient sample of 97,499 with first-time MI, and 3)
      all published studies until beginning of June 2011 examining statin treatment on
      new-onset and recurrent AF in patients not undergoing cardiac surgery. This
      thesis revealed that statins did not lower the incidence or the time to new-onset
      AF in patients with asymptomatic AS. However, statin treatment showed an
      independently preventive effect on new-onset AF, including type-dependent effect
      and a trend to dosage-dependent effect. In addition, this thesis showed that good
      compliance to statin treatment was important to prevent new-onset AF. Finally,
      the meta-analysis in this PhD thesis showed a preventive effect in the
      observational studies although this effect was absent in the randomized
      controlled trials. Based on this PhD thesis, although there might be an effect in
      MI patients, primary statin treatment to prevent new-onset AF cannot be
      recommended in AS patients or in patients not undergoing cardiac surgery. 

PMID- 24083536
TI  - Life after stoma creation.
AB  - BACKGROUND: Stoma creation is a surgical operation where the surgeon makes an
      artificial opening on the abdomen from where the bowel is taken out. It is a
      radical treatment with permanent physical signs of bodily change. In general, it
      leads to loss of a central and personal physical function, as well as an
      alteration in the bodily design. Research in the field may provide additional
      information about central elements when adapting to life with a stoma. There are
      currently no studies that adequately focus on the relationship between health
      related quality of life and stoma construction in a Danish context, neither for
      temporary or permanent construction, nor in relation to the importance of stoma
      handling. PURPOSE: The overall objective of the study was to investigate health
      related quality of life related to stoma creation and patient education.
      Methodologically, the project was implemented as a mixed methods study in which
      qualitative interview studies and two systematic literature reviews identified
      interventions, which were subsequently tested in a clinical case/control study.
      Finally the case/control study was made subject to an economic analysis. The
      project is based on 6 papers reporting the results. ARTICLE 1: Impact of a
      temporary stoma on patients everyday-lives: feelings of uncertainty while waiting
      for closure of the stoma. The study included 7 participants who were interviewed
      in focus groups. The results indicated that patients experienced a high degree of
      uncertainty in connection with the stoma being temporary. At the same time,
      participants had a strong need to control both their physical appearance and
      their changed bodily functions. Participants opted for education programs
      involving teachers with a stoma. ARTICLE 2: Learning to live with a Permanent
      Intestinal Ostomy: Impact on everyday life and Educational Needs. The study
      included 15 participants who were interviewed in groups related to whether they
      were treated for cancer or non-cancer. The results showed that participants often
      experienced the stoma as a taboo, and emotions related to stigma were identified.
      In addition, participants were influenced by the stoma in various ways, and the
      stoma imposed some restrictions on the participants. Participants pointed at
      group-based education, as well as the involvement of teachers who had a stoma.
      ARTICLE 3: Spouses of patients with a stoma lack information and support and are
      restricted in their social and sexual life: a systematic review. The study
      included 6 articles based on quantitative and qualitative data showing that
      spouses were affected in several ways by the construction of the stoma. The
      results pointed at spouses not being informed and supported sufficiently by
      neither enterostoma therapists or surgeons. ARTICLE 4: Patient education has a
      positive effect in patients with a stoma - a systematic review The study included
      7 studies, all with quantitative results. They showed that patient education had
      a positive impact in several areas including shorter hospital stay, less time
      until proficiency in stoma management is reached, an increase in quality of life,
      increased knowledge about the stoma, and increased self-efficacy. ARTICLE 5:
      Health-related quality of life increases when patients with a stoma attend
      patient education - a case/control study. The study included 50 participants
      shortly after stoma creation. The results showed that the disease-specific
      quality of life was significantly increased in the intervention group, while
      generic health-related quality of life was positively affected in different
      dimensions in both groups. ARTICLE 6: Decreased costs with patient education
      after stoma creation. The study was an economic analysis based on participants in
      Article 5. The results indicated that there were fewer unplanned re-admissions
      related to the stoma, and that patients in the intervention group did not visit
      the general practitioner as much as patients in the control group. Furthermore,
      we found that the average cost per patient did not increase when establishing a
      patient education program. CONCLUSION: The thesis concludes that patient
      education has a positive impact on patients' quality of life, and that costs are
      reduced. At the same time, it is concluded that living with a stoma is a complex
      situation, which also involves spouses and close relatives, and that patient
      education must be based on multiple interventions that are not all explored in
      this project.

PMID- 24083537
TI  - SORL1 genetic variants modulate risk of amnestic mild cognitive impairment in
      northern Han Chinese.
AB  - The neuronal sortilin-related receptor (SORL1) has been reported to modulate the
      risk of Alzheimer's disease (AD) in a variety of populations, but replication
      studies have been inconsistent. Amnestic mild cognitive impairment (aMCI) is
      characterized by episodic memory impairment and represents the prodromal stage of
      AD. However, the relationship between SORL1 and aMCI remains unclear. This study
      aimed to investigate the relationship between SORL1 genetic variation and aMCI in
      the Han Chinese population. We conducted a case-control study using a single
      nucleotide polymorphism (SNP), rs668387 (SNP8), in the 5' region of SORL1, and
      three SNPs [rs2070045 (SNP19), rs3824968 (SNP23), rs2282649 (SNP24)] in the 3'
      region of SORL1, along with a haplotype analysis, in 139 aMCI patients and 213
      cognitively-healthy controls from a northern Han Chinese population. We observed
      that SNP19 had a significantly different allele frequency between aMCI patients
      and controls (p = 0.006). Moreover, the GAT haplotype at SNPs 19-23-24 was
      associated with an increased risk of aMCI [odds ratio (OR) 1.377], while the TTC
      haplotype at SNPs 19-23-24 was associated with a decreased risk (OR 0.708). These
      results indicated that the SNPs in the 3' region of SORL1 are associated with
      aMCI in northern Han Chinese. 

PMID- 24083538
TI  - A novel small molecule methyltransferase is important for virulence in Candida
      albicans.
AB  - Candida albicans is an opportunistic pathogen capable of causing life-threatening
      infections in immunocompromised individuals. Despite its significant health
      impact, our understanding of C. albicans pathogenicity is limited, particularly
      at the molecular level. One of the largely understudied enzyme families in C.
      albicans are small molecule AdoMet-dependent methyltransferases (smMTases), which
      are important for maintenance of cellular homeostasis by clearing toxic
      chemicals, generating novel cellular intermediates, and regulating intra- and
      interspecies interactions. In this study, we demonstrated that C. albicans Crg1
      (CaCrg1) is a bona fide smMTase that interacts with the toxin in vitro and in
      vivo. We report that CaCrg1 is important for virulence-related processes such as
      adhesion, hyphal elongation, and membrane trafficking. Biochemical and genetic
      analyses showed that CaCrg1 plays a role in the complex sphingolipid pathway: it
      binds to exogenous short-chain ceramides in vitro and interacts genetically with
      genes of glucosylceramide pathway, and the deletion of CaCRG1 leads to
      significant changes in the abundance of phytoceramides. Finally we found that
      this novel lipid-related smMTase is required for virulence in the waxmoth
      Galleria mellonella, a model of infection. 

PMID- 24083539
TI  - Iron contamination during in-field milling of millet and sorghum.
AB  - Nutritionally, contaminant iron in foods may lead to overestimation of the
      satisfaction of iron requirement while iron deficiencies remain a widespread
      health problem. Iron contamination was measured in millet and sorghum grains
      after decortication and in-field milling using different equipments in Burkina
      Faso. Total iron content did not change significantly after decortication,
      probably due to a balance between losses resulting from the removal of iron-rich
      peripheral parts and contamination. Total iron contents increased significantly
      after mechanical milling irrespective of whether iron or corundum grindstones
      were used. Contamination was highly variable, ranging from 3 to 6 mg iron/100 g
      DM, and was mainly due to wear of the milling equipment. After in vitro digestion
      of traditional cereal dishes prepared with iron-contaminated or uncontaminated
      flours, the contaminant iron was found mainly in the insoluble fraction. Only in
      sorghum was a small proportion (4%) bioaccessible, showing that contaminant iron
      has poor nutritional interest. 

PMID- 24083540
TI  - Preparation of polysubstituted isochromanes by addition of ortho-lithiated
      aryloxiranes to enaminones.
AB  - The reaction of ortho-lithiated aryloxiranes with various enaminones
      straightforwardly affords new functionalized isochromanes as mixtures of two
      epimeric stereoisomers in reasonable to very good yields (50-90%). The two
      diastereomers, which show a high structural variability, can be easily separated
      by column chromatography. 

PMID- 24083541
TI  - Oligonucleotides as targets and cellular probes.

PMID- 24083542
TI  - Instrumental activity of daily living limitations and supports in a clinic
      population of low-income Puerto Rican elderly adults with chronic diseases.
AB  - Latino older adults in the United States have disproportionately high rates of
      chronic and disabling medical conditions. Puerto Ricans have a higher prevalence
      of several chronic medical conditions and higher rates of functional disability
      than other Latinos. Earlier studies have documented that Puerto Rican older
      adults traditionally have relied mostly on family members for assistance with
      their functional needs, with low use of formal support services, but little is
      known about their functional help needs and caregiving practices. This study
      examined independent living and caregiving practices of community-dwelling Puerto
      Rican older adults in western New York using a mixed-methods approach with a
      sample of 49 individuals attending an inner-city primary care clinic. Standard
      instruments were used to obtain information on socioeconomic and health status
      and functional ability. Forty participants who needed help with any instrumental
      activities of daily living (IADLs) were probed qualitatively for how their needs
      were addressed. Participants averaged six chronic medical conditions, mean age
      was 76.2 +/- 5.3, most reported annual household income of $15,000 or less and
      had low fluency in English, and all had healthcare insurance. For the most part,
      participants' children and spouses were primary caregivers, and few used formal
      support services. Nearly one-third reported having insufficient help. Qualitative
      findings elucidated how IADL needs were addressed. In this sample of indigent
      Puerto Rican older adults, most needed help with IADLs. Although family members
      most often helped, one-third had unmet or undermet needs. Linguistically and
      culturally congruent formal support services are still needed for Puerto Rican
      older adults and their family caregivers.

PMID- 24083543
TI  - Patient Activation through Counseling and Exercise--Acute Leukemia (PACE-AL)--a
      randomized controlled trial.
AB  - BACKGROUND: Patients with acute leukemia experience a substantial symptom burden
      and are at risk of developing infections throughout the course of repeated cycles
      of intensive chemotherapy. Physical activity in recent years has been a strategy
      for rehabilitation in cancer patients to remedy disease and treatment related
      symptoms and side effects. To date, there are no clinical practice exercise
      guidelines for patients with acute leukemia undergoing induction and
      consolidation chemotherapy. A randomized controlled trial is needed to determine
      if patients with acute leukemia can benefit by a structured and supervised
      counseling and exercise program. METHODS/DESIGN: This paper presents the study
      protocol: Patient Activation through Counseling and Exercise--Acute Leukemia
      (PACE-AL) trial, a two center, randomized controlled trial of 70 patients with
      acute leukemia (35 patients/study arm) following induction chemotherapy in the
      outpatient setting. Eligible patients will be randomized to usual care or to the
      12 week exercise and counseling program. The intervention includes 3 hours + 30
      minutes per week of supervised and structured aerobic training (moderate to high
      intensity 70-80%) on an ergometer cycle, strength exercises using hand weights
      and relaxation exercise. Individual health counseling sessions include a self
      directed home walk program with a step counter. The primary endpoint is
      functional performance/exercise capacity (6 minute walk distance). The secondary
      endpoints are submaximal VO2 max test, sit to stand and bicep curl test, physical
      activity levels, patient reported outcomes (quality of life, anxiety and
      depression, symptom prevalence, intensity and interference). Evaluation of
      clinical outcomes will be explored including incidence of infection,
      hospitalization days, body mass index, time to recurrence and survival.
      Qualitative exploration of patients' health behavior and experiences. DISCUSSION:
      PACE-AL will provide evidence of the effect of exercise and health promotion
      counseling on functional and physical capacity, the symptom burden and quality of
      life in patients with acute leukemia during out patient management. The results
      will inform clinical practice exercise guidelines and rehabilitation programs for
      patients undergoing treatment for acute leukemia. Optimizing the treatment and
      care pathway may ease the transition for patients from illness to the resumption
      of everyday activities. TRIAL REGISTRATION: ClinicalTrials.gov Identifier:
      NCT01404520.

PMID- 24083544
TI  - Family history and risk of ductal carcinoma in situ and triple negative breast
      cancer in a Han Chinese population: a case-control study.
AB  - BACKGROUND: The association between family history and risk of triple negative
      breast cancer and ductal carcinoma in situ (DCIS) has not been well investigated,
      especially in Asian populations. We investigated the association between family
      history and risk of DCIS or triple negative breast cancer in a Han Chinese
      population. METHODS: A case-control study, comprising 926 breast cancer patients
      and 1,187 benign breast disease controls, was conducted in our hospital.
      Multivariate logistic regression was used to assess the relationships between
      family history and risk of DCIS or triple negative breast cancer. RESULTS:
      Subjects with a family history of breast cancer had higher breast cancer risk
      than those without a family history (odds ratio (OR) = 2.11, 95% confidence
      interval (CI) = 1.26 to 3.52). Family history was not significantly associated
      with an increased risk of DCIS (OR = 1.27, 95% CI = 0.36 to 4.46), while family
      history was significantly associated with an increased risk of invasive breast
      cancer (OR = 2.22, 95% CI = 1.32 to 3.75), irrespective of triple negative breast
      cancer (OR = 3.35, 95% CI = 1.43 to 7.88) or non-triple negative breast cancer
      (OR = 2.14, 95% CI = 1.21 to 3.80). CONCLUSION: Our results indicate that having
      a family history of breast cancer is associated with an increased risk of triple
      negative breast cancer with a magnitude of association similar to that for non
      triple negative breast cancer. Furthermore, family history is not significantly
      associated with an increased risk of DCIS. Future cohort studies with larger
      sample sizes are still needed to explore these relationships.

PMID- 24083545
TI  - The emerging role of ibrutinib in the treatment of chronic lymphocytic leukemia.
AB  - Drugs that selectively inhibit Bruton's tyrosine kinase (BTK), such as the new
      orally administered agent ibrutinib, are currently under investigation for the
      treatment of several types of B-cell malignancies. In this article, the authors
      present results of a Phase Ib/II study of ibrutinib in 85 patients with relapsed
      or refractory chronic lymphocytic leukemia (CLL). The enthusiasm generated by
      this paper relies on the fact that ibrutinib given orally on a daily basis
      produces very high response rates that are durable with minimal side effects.
      Interestingly, the favorable therapeutic index of ibrutinib may facilitate its
      use in combination with other agents active in the treatment of CLL. In addition,
      the use of an effective oral agent like ibrutinib whose efficacy does not
      translate into a high burden of toxicity should be considered in choosing therapy
      in the elderly. A challenging issue with ibrutinib is the possibility of
      overcoming chemotherapy in the treatment of CLL.

PMID- 24083546
TI  - Cited2 is required for the maintenance of glycolytic metabolism in adult
      hematopoietic stem cells.
AB  - Mammalian adult hematopoietic stem cells (HSCs) reside in the hypoxic bone marrow
      microenvironment and display a distinct metabolic phenotype compared with their
      progenitors. It has been proposed that HSCs generate energy mainly through
      anaerobic glycolysis in a pyruvate dehydrogenase kinase (Pdk)-dependent manner.
      Cited2 is an essential regulator for HSC quiescence, apoptosis, and function.
      Herein, we show that conditional deletion of Cited2 in murine HSCs results in
      elevated levels of reactive oxygen species, decreased cellular glutathione
      content, increased mitochondrial activity, and decreased glycolysis. At the
      molecular level, Cited2 deficiency significantly reduced the expression of genes
      involved in metabolism, such as Pdk2, Pdk4, and lactate dehydrogenases B and D
      (LDHB and LDHD). Cited2-deficient HSCs also exhibited increased Akt signaling,
      concomitant with elevated mTORC1 activity and phosphorylation of FoxOs. Further,
      inhibition of PI3/Akt, but not mTORC1, partially rescued the repression of Pdk4
      caused by deletion of Cited2. Altogether, our results suggest that Cited2 is
      required for the maintenance of adult HSC glycolytic metabolism likely through
      regulating Pdk2, Pdk4, LDHB, LDHD, and Akt activity. 

PMID- 24083547
TI  - Poly(trehalose): sugar-coated nanocomplexes promote stabilization and effective
      polyplex-mediated siRNA delivery.
AB  - When nanoparticles interact with their environment, the nature of that
      interaction is governed largely by the properties of its outermost surface layer.
      Here, we exploit the exceptional properties of a common disaccharide, trehalose,
      which is well-known for its unique biological stabilization effects. To this end,
      we have developed a synthetic procedure that readily affords a polymer of this
      disaccharide, poly(methacrylamidotrehalose) or "poly(trehalose)" and diblock
      copolycations containing this polymer with 51 repeat units chain extended with
      aminoethylmethacrylamide (AEMA) at three degrees of polymerization (n = 34, 65,
      and 84). Two series of experiments were conducted to study these diblock
      copolymers in detail and to compare their properties to two control polymers [PEG
      P(AEMA) and P(AEMA)]. First, we demonstrate that the poly(trehalose) coating
      ensures colloidal stability of polyplexes containing siRNA in the presence of
      high salt concentrations and serum proteins. Poly(trehalose) retains the ability
      of trehalose to lower the phase transition energy associated with water freezing
      and can protect siRNA polyplexes during freeze-drying, allowing complete
      nanoparticle resuspension without loss of biological function. Second, we show
      that siRNA polyplexes coated with poly(trehalose) have exceptional cellular
      internalization into glioblastoma cells that proceeds with zero-order kinetics.
      Moreover, the amount of siRNA delivered by poly(trehalose) block copolycations
      can be controlled by the siRNA concentration in cell culture media. Using
      confocal microscopy we show that trehalose-coated polyplexes undergo active
      trafficking in cytoplasm upon internalization and significant siRNA-induced
      target gene down-regulation was achieved with an IC50 of 19 nM. These findings
      coupled with a negligible cytotoxicity suggests that poly(trehalose) has the
      potential to serve as an important component of therapeutic nanoparticle
      formulations of nucleic acids and has great promise to be extended as a new
      coating for other nanobased technologies and macromolecules, in particular, those
      related to nanomedicine applications. 

PMID- 24083548
TI  - On the alert: future priorities for alerts in clinical decision support for
      computerized physician order entry identified from a European workshop.
AB  - BACKGROUND: Clinical decision support (CDS) for electronic prescribing systems
      (computerized physician order entry) should help prescribers in the safe and
      rational use of medicines. However, the best ways to alert users to unsafe or
      irrational prescribing are uncertain. Specifically, CDS systems may generate too
      many alerts, producing unwelcome distractions for prescribers, or too few alerts
      running the risk of overlooking possible harms. Obtaining the right balance of
      alerting to adequately improve patient safety should be a priority. METHODS: A
      workshop funded through the European Regional Development Fund was convened by
      the University Hospitals Birmingham NHS Foundation Trust to assess current
      knowledge on alerts in CDS and to reach a consensus on a future research agenda
      on this topic. Leading European researchers in CDS and alerts in electronic
      prescribing systems were invited to the workshop. RESULTS: We identified
      important knowledge gaps and suggest research priorities including (1) the need
      to determine the optimal sensitivity and specificity of alerts; (2) whether
      adaptation to the environment or characteristics of the user may improve alerts;
      and (3) whether modifying the timing and number of alerts will lead to
      improvements. We have also discussed the challenges and benefits of using
      naturalistic or experimental studies in the evaluation of alerts and suggested
      appropriate outcome measures. CONCLUSIONS: We have identified critical problems
      in CDS, which should help to guide priorities in research to evaluate alerts. It
      is hoped that this will spark the next generation of novel research from which
      practical steps can be taken to implement changes to CDS systems that will
      ultimately reduce alert fatigue and improve the design of future systems.

PMID- 24083549
TI  - Proteomic and transcriptomic analyses of fecundity in the brown planthopper
      Nilaparvata lugens (Stal).
AB  - As an r-strategy insect species, the brown planthopper (BPH) Nilaparvata lugens
      (Stal) is a serious pest of rice crops in the temperate and tropical regions of
      Asia and Australia, which may be due to its robust fecundity. Here we combined 2
      DE comparative proteomic and RNA-seq transcriptomic analyses to identify
      fecundity-related proteins and genes. Using high- and low-fecundity populations
      as sample groups, a total of 54 and 75 proteins were significantly altered in the
      third and sixth day brachypterous female stages, respectively, and 39 and 54 of
      these proteins were identified by MALDI-TOF/TOF MS. In addition, 71,966 unigenes
      were quantified by Illumina sequencing. On the basis of the transcriptomic
      analysis, 7408 and 1639 unigenes demonstrated higher expression levels in the
      high-fecundity population in the second day brachypterous female adults and the
      second day fifth instar nymphs, respectively, and 411 unigenes were up-regulated
      in both groups. Of these dozens of proteins and thousands of unigenes, five were
      differentially expressed at both the protein and mRNA levels at all four time
      points, suggesting that these genes may regulate fecundity. Glutamine synthetase
      (GS) was chosen for further functional studies. RNAi knockdown of the GS gene
      reduced the fecundity of N. lugens by 64.6%, disrupted ovary development, and
      inhibited vitellogenin (Vg) expression. Our results show that a combination of
      proteomic and transcriptomic analyses provided five candidate proteins and genes
      for further study. The knowledge gained from this study may lead to a more
      fundamental understanding of the fecundity of this important agricultural insect
      pest.

PMID- 24083550
TI  - Polymorphism of ERCC2 Asp312Asn with lung cancer risk: evidence from 20,101
      subjects.
AB  - The association between excision repair cross complementing group 2 (ERCC2)
      Asp312Asn polymorphism and lung cancer has been reported by many articles
      recently, but the results were controversial and inconclusive. Therefore, a meta
      analysis was conducted to assess the relationship between them. Pooled odds
      ratios (ORs) with 95% confidence intervals (CIs) were used to assess the strength
      of association. A total of 22 full studies with 20,101 subjects (8719 cases and
      11,382 controls) were included in our research. The meta-analysis result showed
      that no significant association was found between ERCC2 Asp312Asn polymorphism
      and lung cancer in overall analysis (AA vs. GG, OR=1.023, 95% CI=0.824-1.270,
      p=0.838; AG vs. GG, OR=1.003, 95% CI=0.936-1.074, p=0.942; AA+AG vs. GG,
      OR=1.013, 95% CI=0.949-1.082, p=0.697; AA vs. AG+GG, OR=1.033, 95% CI=0.841
      1.270, p=0.755). In subset analyses of stratified ethnicity, significantly
      increased risk was found among Asians (AA vs. GG, OR=3.212, 95% CI=1.518-6.795,
      p=0.002; AA vs. AG+GG, OR=3.174, 95% CI=1.500-6.712, p=0.003), whereas the
      association was not found among Caucasians under any genetic models. When
      analyses were conducted based on the study design, it indicated that the risk of
      lung cancer might be significantly increased in a hospital-based study (AA vs.
      GG, OR=1.323, 95% CI=1.096-1.596, p=0.004; AA+AG vs. GG, OR=1.109, 95% CI=1.000
      1.229, p=0.050; AA vs. AG+GG, OR=1.285, 95% CI=1.076-1.535, p=0.006). In
      addition, a significantly increased risk for nonsmokers was detected under the
      dominant model (AA+AG vs. GG, OR=1.460, 95% CI=1.095-1.948, p=0.010). In
      conclusion, this meta-analysis suggested ERCC2 Asp312Asn polymorphism may
      increase the risk of lung cancer among Asians, whereas not among Caucasians. 

PMID- 24083551
TI  - Biased processing of sad faces: an ERP marker candidate for depression
      susceptibility.
AB  - Depression has been associated with task-relevant increased attention toward
      negative information, reduced attention toward positive information, or reduced
      inhibition of task-irrelevant negative information. This study employed
      behavioural and psychophysiological measures (event-related potentials; ERP) to
      examine whether groups with risk factors for depression (past depression, current
      dysphoria) would show attentional biases or inhibitory deficits related to
      viewing facial expressions. In oddball task blocks, young adult participants
      responded to an infrequently presented target emotion (e.g., sad) and inhibited
      responses to an infrequently presented distracter emotion (e.g., happy) in the
      context of frequently presented neutral stimuli. Previous depression was uniquely
      associated with greater P3 ERP amplitude following sad targets, reflecting a
      selective attention bias. Also, dysphoric individuals less effectively inhibited
      responses to sad distracters than non-dysphoric individuals according to
      behavioural data, but not psychophysiological data. Results suggest that
      depression risk may be most reliably characterised by increased attention toward
      others' depressive facial emotion. 

PMID- 24083552
TI  - Effects of a delocalizable cation on the headgroup of gemini lipids on the
      lipoplex-type nanoaggregates directly formed from plasmid DNA.
AB  - Lipoplex-type nanoaggregates prepared from pEGFP-C3 plasmid DNA (pDNA) and mixed
      liposomes, with a gemini cationic lipid (CL) [1,2-bis(hexadecyl imidazolium)
      alkanes], referred as (C16Im)2Cn (where Cn is the alkane spacer length, n = 2, 3,
      5, or 12, between the imidazolium heads) and DOPE zwitterionic lipid, have been
      analyzed by zeta potential, gel electrophoresis, SAXS, cryo-TEM, fluorescence
      anisotropy, transfection efficiency, fluorescence confocal microscopy, and cell
      viability/cytotoxicity experiments to establish a structure-biological activity
      relationship. The study, carried out at several mixed liposome compositions,
      alpha, and effective charge ratios, rhoeff, of the lipoplex, demonstrates that
      the transfection of pDNA using CLs initially requires the determination of the
      effective charge of both. The electrochemical study confirms that CLs with a
      delocalizable positive charge in their headgroups yield an effective positive
      charge that is 90% of their expected nominal one, while pDNA is compacted
      yielding an effective negative charge which is only 10-25% than that of the
      linear DNA. SAXS diffractograms show that lipoplexes formed by CLs with shorter
      spacer (n = 2, 3, or 5) present three lamellar structures, two of them in
      coexistence, while those formed by CL with longest spacer (n = 12) present two
      additional inverted hexagonal structures. Cryo-TEM micrographs show
      nanoaggregates with two multilamellar structures, a cluster-type (at low alpha
      value) and a fingerprint-type, that coexist with the cluster-type at moderate
      alpha composition. The optimized transfection efficiency (TE) of pDNA, in
      HEK293T, HeLa, and H1299 cells was higher using lipoplexes containing gemini CLs
      with shorter spacers at low alpha value. Each lipid formulation did not show any
      significant levels of toxicity, the reported lipoplexes being adequate DNA
      vectors for gene therapy and considerably better than both Lipofectamine 2000 and
      CLs of the 1,2-bis(hexadecyl ammnoniun) alkane series, recently reported. 

PMID- 24083553
TI  - Myoglobin on silica: a case study of the impact of adsorption on protein
      structure and dynamics.
AB  - If protein structure and function changes upon adsorption are well documented,
      modification of adsorbed protein dynamics remains a blind spot, despite its
      importance in biological processes. The adsorption of metmyoglobin on a silica
      surface was studied by isotherm measurements, microcalorimetry, circular
      dichroism, and UV-visible spectroscopy to determine the thermodynamic parameters
      of protein adsorption and consequent structure modifications. The mean square
      displacement and the vibrational densities of states of the adsorbed protein were
      measured by elastic and inelastic neutron scattering experiments. A decrease of
      protein flexibility and depletion in low frequency modes of myoglobin after
      adsorption on silica was observed. Our results suggest that the structure loss
      itself is not the entropic driving force of adsorption.

PMID- 24083554
TI  - Microbial community composition of Tirez lagoon (Spain), a highly sulfated
      athalassohaline environment.
AB  - BACKGROUND: The aim was to study the seasonal microbial diversity variations of
      an athalassohaline environment with a high concentration of sulfates in Tirez
      lagoon (La Mancha, Spain). Despite the interest in these types of environments
      there is scarce information about their microbial ecology, especially on their
      anoxic sediments. RESULTS: We report the seasonal microbial diversity of the
      water column and the sediments of a highly sulfated lagoon using both molecular
      and conventional microbiological methods. Algae and Cyanobacteria were the main
      photosynthetic primary producers detected in the ecosystem in the rainy season.
      Also dinoflagelates and filamentous fungi were identified in the brines. The
      highest phylotype abundance in water and sediments corresponded to members of the
      bacterial phylum Proteobacteria, mainly of the Gamma- and Alphaproteobacteria
      classes. Firmicutes and Actinobacteria were isolated and identified in Tirez
      brines and sediment samples. Halophilic sulfate reducing Deltaproteobacteria were
      also detected (Desulfohalobium). CONCLUSIONS: Important differences have been
      found in the microbial diversity present in the Tirez water column and the
      sediments between the wet and dry seasons. Also the Tirez lagoon showed a high
      richness of the bacterial Alpha- and Deltaproteobacteria, Bacteroidetes,
      Firmicutes, Actinobacteria and for the archaeal Euryarchaeota.

PMID- 24083555
TI  - Improvement of plant growth and seed yield in Jatropha curcas by a novel nitrogen
      fixing root associated Enterobacter species.
AB  - BACKGROUND: Jatropha curcas L. is an oil seed producing non-leguminous tropical
      shrub that has good potential to be a fuel plant that can be cultivated on
      marginal land. Due to the low nutrient content of the targeted plantation area,
      the requirement for fertilizer is expected to be higher than other plants. This
      factor severely affects the commercial viability of J. curcas. RESULTS: We
      explored the feasibility to use endophytic nitrogen-fixing bacteria that are
      native to J. curcas to improve plant growth, biomass and seed productivity. We
      demonstrated that a novel N-fixing endophyte, Enterobacter sp. R4-368, was able
      to colonize in root and stem tissues and significantly promoted early plant
      growth and seed productivity of J. curcas in sterilized and non-sterilized soil.
      Inoculation of young seedling led to an approximately 57.2% increase in seedling
      vigour over a six week period. At 90 days after planting, inoculated plants
      showed an average increase of 25.3%, 77.7%, 27.5%, 45.8% in plant height, leaf
      number, chlorophyll content and stem volume, respectively. Notably, inoculation
      of the strain led to a 49.0% increase in the average seed number per plant and
      20% increase in the average single seed weight when plants were maintained for
      1.5 years in non-sterilized soil in pots in the open air. Enterobacter sp. R4-368
      cells were able to colonize root tissues and moved systemically to stem tissues.
      However, no bacteria were found in leaves. Promotion of plant growth and leaf
      nitrogen content by the strain was partially lost in nifH, nifD, nifK knockout
      mutants, suggesting the presence of other growth promoting factors that are
      associated with this bacterium strain. CONCLUSION: Our results showed that
      Enterobacter sp. R4-368 significantly promoted growth and seed yield of J.
      curcas. The application of the strains is likely to significantly improve the
      commercial viability of J. curcas due to the reduced fertilizer cost and improved
      oil yield.

PMID- 24083557
TI  - Bridging research and environmental regulatory processes: the role of knowledge
      brokers.
AB  - Federal funding agencies increasingly require research investigators to ensure
      that federally sponsored research demonstrates broader societal impact.
      Specifically, the National Institutes of Environmental Health Sciences (NIEHS)
      Superfund Research Program (SRP) requires research centers to include research
      translation and community engagement cores to achieve broader impacts, with
      special emphasis on improving environmental health policies through better
      scientific understanding. This paper draws on theoretical insights from the
      social sciences to show how incorporating knowledge brokers in research centers
      can facilitate translation of scientific expertise to influence regulatory
      processes and thus promote public health. Knowledge brokers connect academic
      researchers with decision-makers, to facilitate the translation of research
      findings into policies and programs. In this article, we describe the stages of
      the regulatory process and highlight the role of the knowledge broker and
      scientific expert at each stage. We illustrate the cooperation of knowledge
      brokers, scientific experts and policymakers using a case from the Brown
      University (Brown) SRP. We show how the Brown SRP incorporated knowledge brokers
      to engage scientific experts with regulatory officials around the emerging public
      health problem of vapor intrusion (VI). In the Brown SRP, the knowledge broker
      brought regulatory officials into the research process, to help scientific
      experts understand the critical nature of this emerging public health threat, and
      helped scientific experts develop a research agenda that would inform the
      development of timely measures to protect public health. Our experience shows
      that knowledge brokers can enhance the impact of environmental research on public
      health by connecting policy decision-makers with scientific experts at critical
      points throughout the regulatory process. 

PMID- 24083558
TI  - Monodisperse pattern nanoalloying for synergistic intermetallic catalysis.
AB  - Nanoscale alloys attract enormous research attentions in catalysis, magnetics,
      plasmonics and so on. Along with multicomponent synergy, quantum confinement and
      extreme large surface area of nanoalloys offer novel material properties,
      precisely and broadly tunable with chemical composition and nanoscale dimension.
      Despite substantial progress of nanoalloy synthesis, the randomized positional
      arrangement and dimensional/compositional inhomogeneity of nanoalloys remain
      significant technological challenges for advanced applications. Here we present a
      generalized route to synthesize single-crystalline intermetallic nanoalloy arrays
      with dimensional and compositional uniformity via self-assembly. Specific
      electrostatic association of multiple ionic metal complexes within self-assembled
      nanodomains of block copolymers generated patterned monodisperse
      bimetallic/trimetallic nanoalloy arrays consisting of various elements, including
      Au, Co, Fe, Pd, and Pt. The precise controllability of size, composition, and
      intermetallic crystalline structure of nanoalloys facilitated tailored
      synergistic properties, such as accelerated catalytic growth of vertical carbon
      nanotubes from Fe-Co nanoalloy arrays. 

PMID- 24083556
TI  - Selective photoinactivation of Candida albicans in the non-vertebrate host
      infection model Galleria mellonella.
AB  - BACKGROUND: Candida spp. are recognized as a primary agent of severe fungal
      infection in immunocompromised patients, and are the fourth most common cause of
      bloodstream infections. Our study explores treatment with photodynamic therapy
      (PDT) as an innovative antimicrobial technology that employs a nontoxic dye,
      termed a photosensitizer (PS), followed by irradiation with harmless visible
      light. After photoactivation, the PS produces either singlet oxygen or other
      reactive oxygen species (ROS) that primarily react with the pathogen cell wall,
      promoting permeabilization of the membrane and cell death. The emergence of
      antifungal-resistant Candida strains has motivated the study of antimicrobial PDT
      (aPDT) as an alternative treatment of these infections. We employed the
      invertebrate wax moth Galleria mellonella as an in vivo model to study the
      effects of aPDT against C. albicans infection. The effects of aPDT combined with
      conventional antifungal drugs were also evaluated in G. mellonella. RESULTS: We
      verified that methylene blue-mediated aPDT prolonged the survival of C. albicans
      infected G. mellonella larvae. The fungal burden of G. mellonella hemolymph was
      reduced after aPDT in infected larvae. A fluconazole-resistant C. albicans strain
      was used to test the combination of aPDT and fluconazole. Administration of
      fluconazole either before or after exposing the larvae to aPDT significantly
      prolonged the survival of the larvae compared to either treatment alone.
      CONCLUSIONS: G. mellonella is a useful in vivo model to evaluate aPDT as a
      treatment regimen for Candida infections. The data suggests that combined aPDT
      and antifungal therapy could be an alternative approach to antifungal-resistant
      Candida strains.

PMID- 24083560
TI  - Retraction of "Derivation and genetic modification of embryonic stem cells from
      disease-model inbred rat strains".

PMID- 24083559
TI  - Astragalus injection protects cerebral ischemic injury by inhibiting neuronal
      apoptosis and the expression of JNK3 after cerebral ischemia reperfusion in rats.
AB  - BACKGROUND: Astragalus is a widely used traditional Chinese medicine and has been
      proven beneficial for many aspects of human health. It is important to explore
      the neuroprotective effect and mechanism of astragalus injection in cerebral
      ischemia reperfusion injury. METHODS: The focal cerebral ischemic model with
      middle cerebral artery occlusion (MCAO) reperfusion was established by Longa's
      method in healthy adult male Wistar rats, and treated by injecting
      intraperitoneally astragalus injection (3 ml/kg). The neurobehavioral function of
      rats was evaluated by Longa's test. The cerebral blood flow (CBF) was measured by
      laser Doppler flowmetry and the cerebral infarct volume was calculated by
      tetrazolium chloride (TTC) stain. The shape and structure of neurons in
      parahippocampal area was observed by HE stain and the neuronal apoptosis was
      detected by terminal deoxynucleotidyl transferase mediated dUTP nick end labeling
      (TUNEL) and flow cytometry. The expressions of c-jun N-terminal kinase 3 (JNK3)
      mRNA and protein were determined by RT-PCR and immunohistochemical assay and
      Western blotting respectively. RESULTS: After treatment with astragalus
      injection, the expressions of JNK3 mRNA and protein reduced significantly, the
      number of neuronal apoptosis minus, the cerebral infarct volume shrink, the
      neuronal shape-structure and animal neurobehavioral function improved
      significantly than those in model rats. CONCLUSIONS: It is suggested that
      astragalus injection could inhibit neuronal apoptosis, reduce infarct volume and
      improve neurobehavioral function by down-regulating the expression of JNK3 gene
      after cerebral ischemia reperfusion injury in rats.

PMID- 24083561
TI  - Treatment for hemophilia: recombinant versus plasma-derived coagulation factors -
      controversy and debate forever? An ethical medical challenge?

PMID- 24083563
TI  - The protective effects of bilberry and lingonberry extracts against UV light
      induced retinal photoreceptor cell damage in vitro.
AB  - Bilberry extract (B-ext) and lingonberry extract (L-ext) are currently used as
      health supplements. We investigated the protective mechanisms of the B-ext and L
      ext against ultraviolet A (UVA)-induced retinal photoreceptor cell damage.
      Cultured murine photoreceptor (661W) cells were exposed to UVA following
      treatment with B-ext and L-ext and their main constituents (cyanidin,
      delphinidin, malvidin, trans-resveratrol, and procyanidin). B-ext, L-ext, and
      constituents improved cell viability and suppressed ROS generation.
      Phosphorylation of p38 mitogen-activated protein kinase (p38 MAPK), c-Jun N
      terminal kinase (JNK), and protein kinase B (Akt) were analyzed by Western
      blotting. B-ext and cyanidin inhibited phosphorylation of p38 MAPK, and B-ext
      also inhibited phosphorylation of JNK by UVA. L-ext, trans-resveratrol, and
      procyanidin alleviated the reduction of phosphorylated Akt levels by UVA.
      Finally, a cotreatment with B-ext and L-ext showed an additive effect on cell
      viability. Our findings suggest that both B-ext and L-ext endow protective
      effects against UVA-induced retinal damage.

PMID- 24083562
TI  - Tyrosine O-prenyltransferase SirD catalyzes S-, C-, and N-prenylations on
      tyrosine and tryptophan derivatives.
AB  - The tyrosine O-prenyltransferase SirD in Leptosphaeria maculans catalyzes normal
      prenylation of the hydroxyl group in tyrosine as the first committed step in the
      biosynthesis of the phytotoxin sirodesmin PL. SirD also catalyzes normal N
      prenylation of 4-aminophenylalanine and normal C-prenylation at C7 of tryptophan.
      In this study, we found that 4-mercaptophenylalanine and several derivatives of
      tryptophan are also substrates for prenylation by dimethylallyl diphosphate.
      Incubation of SirD with 4-mercaptophenylalanine gave normal S-prenylated
      mercaptophenylalanine. We found that incubation of the enzyme with tryptophan
      gave reverse prenylation at N1 in addition to the previously reported normal
      prenylation at C7. 4-Methyltryptophan also gave normal prenylation at C7 and
      reverse prenylation at N1, whereas 4-methoxytryptophan gave normal and reverse
      prenylation at C7, and 7-methyltryptophan gave normal prenylation at C6 and
      reverse prenylation at N1. The ability of SirD to prenylate at three different
      sites on the indole nucleus, with normal and reverse prenylation at one of the
      sites, is similar to behavior seen for dimethylallyltryptophan synthase. The
      multiple products produced by SirD suggests it and dimethylallyltryptophan
      synthase use a dissociative electrophilic mechanism for alkylation of amino acid
      substrates. 

PMID- 24083564
TI  - Proteomic analysis of the oil palm fruit mesocarp reveals elevated oxidative
      phosphorylation activity is critical for increased storage oil production.
AB  - Palm oil is a highly versatile commodity with wide applications in the food,
      cosmetics, and biofuel industries. Storage oil in the oil palm mesocarp can make
      up a remarkable 80% of its dry mass, making it the oil crop with the richest oil
      content in the world. As such, there has been an ongoing interest in
      understanding the mechanism of oil production in oil palm fruits. To identify the
      proteome changes during oil palm fruit maturation and factors affecting oil yield
      in oil palm fruits, we examined the proteomic profiles of oil palm mesocarps at
      four developing stages--12, 16, 18, and 22 weeks after pollination--by 8-plex
      iTRAQ labeling coupled to 2D-LC and MALDI-TOF/TOF MS. It was found that proteins
      from several important metabolic processes, including starch and sucrose
      metabolism, glycolysis, pentose phosphate shunt, fatty acid biosynthesis, and
      oxidative phosphorylation, were differentially expressed in a concerted manner.
      These increases led to an increase in carbon flux and a diversion of resources
      such as ATP and NADH that are required for lipid biosynthesis. The temporal
      proteome profiles between the high-oil-yielding (HY) and low-oil-yielding (LY)
      fruits also showed significant differences in the levels of proteins involved in
      the regulation of the TCA cycle and oxidative phosphorylation. In particular, the
      expression level of the beta subunit of the ATP synthase complex (complex IV of
      the electron transport chain) was found to be increased during fruit maturation
      in HY but decreased in the LY during the fruit maturation. These results
      suggested that increased energy supply is necessary for augmented oil yield in
      the HY oil palm trees.

PMID- 24083565
TI  - Intellectual ability as a predictor of performance on the Wisconsin Card-Sorting
      Test.
AB  - The purpose of this study was to explore the relationship between intelligence
      and executive functioning in youth. More specifically, the authors hypothesized
      that there would be a positive correlation between scores on the Wechsler
      Intelligence Scale for Children-Fourth Edition General Ability Index (GAI) and
      understanding of sorting principles as measured by percent conceptual-level
      responses on the Wisconsin Card-Sorting Test (WCST). One hundred eighty-five
      children and adolescents completed neuropsychological evaluations. Results
      revealed a curvilinear regression with bright youth (GAI = 115-129) and gifted
      youth (GAI >=130) performing better than average youth (GAI = 90-114) and no
      difference in performance between bright and gifted youth. Additionally, post-hoc
      analyses revealed intelligence in children 5 to 8 years of age and 12 to 16 years
      of age did not significantly predict percent conceptual-level responses, while
      intelligence predicted more than 19% of the variance in percent conceptual-level
      responses for children ages 9 to 11 years old. Findings revealed new evidence
      about the role of intellectual ability in executive functioning among different
      age ranges and have important implications for psychologists, caregivers,
      educators, and other professionals working with this population.

PMID- 24083566
TI  - Impacts of clinicopathologic and operative factors on short-term and long-term
      survival in renal cell carcinoma with venous tumor thrombus extension: a multi
      institutional retrospective study in Japan.
AB  - BACKGROUND: Although the percentage of patients with renal cell carcinoma (RCC)
      extending into venous systems is unexpectedly high, the prognostic impact and
      independency of venous tumor thrombus-related factors on overall survival (OS)
      remain controversial. Furthermore, the prognostic impact of various
      clinicopathologic factors including tumor thrombus-related factors on OS may
      change with elapsed years after the intervention and also with follow-up duration
      of participants. The aim of the study is to explore independent and universal
      predictive preoperative and intraoperative clinicopathologic factors on OS in
      patients with RCC extending into venous systems using subgroup analysis in terms
      of restricted follow-up duration and yearly-based survivors. METHODS: Between
      1980 and 2009, 292 patients diagnosed with RCC with venous tumor thrombus were
      retrospectively registered for this study. The prognostic impacts of various
      clinicopathologic and surgical treatment factors including levels of venous
      thrombus, venous wall invasion status and likelihood of aggressive cytoreductive
      operation, were investigated using Kaplan-Meier method and following multivariate
      Cox proportional hazards model for all patients and those still alive at 1, 2,
      and 3 years of follow-up. To investigate the impact of follow-up duration on the
      statistical analyses, multivariate logistic regression analyses were used to
      explore prognostic factors using restricted data until 1, 2, and 3 years of
      follow-up. RESULTS: The median follow-up duration was 40.4 months. The 5-year OS
      was 47.6%. Several independent predictive factors were identified in each
      subgroup analysis in terms of yearly-based survival and restricted follow-up
      duration. The presence of tumor thrombus invading to venous wall was
      independently related to OS in the full-range follow-up data and in survivors at
      2 and 3 years of follow-up. Using restricted follow-up data until 1, 2, and 3
      years of follow-up, many independent predictive factors changed with follow-up
      duration, but surgical category could be universal and independent predictive
      factors. CONCLUSION: The most universal factors affecting improvement both in
      short-term and long-term survivals could be cytoreductive surgery and absence of
      venous wall invasion. It may mean that feasible aggressive cytoreductive
      operation following more reliable preoperative imaging for predicting venous wall
      invasion status would improve OS for patients with RCC extending into venous
      systems.

PMID- 24083567
TI  - Hydrolytically degradable polymer micelles for drug delivery: a SAXS/SANS kinetic
      study.
AB  - We report kinetic studies of therapeutically highly potent polymer-drug
      conjugates consisting of amphiphilic N-(2-hydroxypropyl) methacrylamide (HPMA)
      based copolymers bearing the anticancer drug doxorubicin (Dox). Highly
      hydrophobic cholesterol moieties as well as the drug were attached to the polymer
      backbone by a pH-sensitive hydrazone bond. Moreover, the structure of the spacer
      between the polymer carrier and the cholesterol moiety differed in order to
      influence the release rate of the hydrophobic moiety, and thus the disintegration
      of the high-molecular-weight micellar nanoparticle structure. We performed time
      dependent SAXS/SANS measurements after changing pH from a typical blood value (pH
      7.2) to that of tumor cells (pH 5.0) to characterize the drug release and changes
      in particle size and shape. Nanoparticles composed of the conjugates containing
      Dox were generally larger than the drug-free ones. For most conjugates,
      nanoparticle growth or decay was observed in the time range of several hours. It
      was established that the growth/decay rate and the steady-state size of
      nanoparticles depend on the spacer structure. From analytical fitting, we
      conclude that the most probable structure of the nanoparticles was a core-shell
      or a core with attached Gaussian chains. We concluded that the spacer structure
      determined the fate of a cholesterol derivative after the pH jump. Fitting
      results for 5alpha-cholestan-3-onecholestan-3-one and cholesteryl-4-oxopentanoate
      (Lev-chol) implied that cholesterol moieties continuously escape from the core of
      the nanoparticle core and concentrate in the hydrophilic shell. In contrast,
      cholest-4-en-3-one spacer prevent cholesterol escaping. Dox moiety release was
      only observed after a change in pH. Such findings justify the model proposed in
      our previous paper. Lastly, the cholesteryl 4-(2-oxopropyl)benzoate (Opb-Chol)
      was a different case where after the release of hydrophobic Opb-Chol moieties,
      the core becomes more compact. The physicochemical mechanisms responsible for the
      scenarios of the different spacers are discussed. 

PMID- 24083568
TI  - Gold(I)-catalyzed asymmetric induction of planar chirality by intramolecular
      nucleophilic addition to chromium-complexed alkynylarenes: asymmetric synthesis
      of planar chiral (1H-isochromene and 1,2-dihydroisoquinoline)chromium complexes.
AB  - Gold(I)-catalyzed asymmetric intramolecular cyclization of prochiral 1,3
      dihydroxymethyl-2-alkynylbenzene or 1,3-bis(carbamate)-2-alkynylbenzene
      tricarbonylchromium complexes with axially chiral diphosphine ligand gave planar
      chiral tricarbonylchromium complexes of 1H-isochromene or 1,2-dihydroisoquinoline
      with high enantioselectivity. An enantiomeric excess of the planar chiral arene
      chromium complexes was largely affected by a combination of axially chiral
      diphosphine(AuCl)2 precatalysts and silver salts. In the case of 1,3
      dihydroxymethyl-2-alkynylbenzene chromium complexes, a system of segphos(AuCl)2
      with AgBF4 resulted in the formation of the corresponding antipode. 

PMID- 24083569
TI  - Improved de-identification of physician notes through integrative modeling of
      both public and private medical text.
AB  - BACKGROUND: Physician notes routinely recorded during patient care represent a
      vast and underutilized resource for human disease studies on a population scale.
      Their use in research is primarily limited by the need to separate confidential
      patient information from clinical annotations, a process that is resource
      intensive when performed manually. This study seeks to create an automated method
      for de-identifying physician notes that does not require large amounts of private
      information: in addition to training a model to recognize Protected Health
      Information (PHI) within private physician notes, we reverse the problem and
      train a model to recognize non-PHI words and phrases that appear in public
      medical texts. METHODS: Public and private medical text sources were analyzed to
      distinguish common medical words and phrases from Protected Health Information.
      Patient identifiers are generally nouns and numbers that appear infrequently in
      medical literature. To quantify this relationship, term frequencies and part of
      speech tags were compared between journal publications and physician notes.
      Standard medical concepts and phrases were then examined across ten medical
      dictionaries. Lists and rules were included from the US census database and
      previously published studies. In total, 28 features were used to train decision
      tree classifiers. RESULTS: The model successfully recalled 98% of PHI tokens from
      220 discharge summaries. Cost sensitive classification was used to weight recall
      over precision (98% F10 score, 76% F1 score). More than half of the false
      negatives were the word "of" appearing in a hospital name. All patient names,
      phone numbers, and home addresses were at least partially redacted. Medical
      concepts such as "elevated white blood cell count" were informative for de
      identification. The results exceed the previously approved criteria established
      by four Institutional Review Boards. CONCLUSIONS: The results indicate that
      distributional differences between private and public medical text can be used to
      accurately classify PHI. The data and algorithms reported here are made freely
      available for evaluation and improvement.

PMID- 24083571
TI  - Consequences of metal-oxide interconversion for C-H bond activation during CH4
      reactions on Pd catalysts.
AB  - Mechanistic assessments based on kinetic and isotopic methods combined with
      density functional theory are used to probe the diverse pathways by which C-H
      bonds in CH4 react on bare Pd clusters, Pd cluster surfaces saturated with
      chemisorbed oxygen (O*), and PdO clusters. C-H activation routes change from
      oxidative addition to H-abstraction and then to sigma-bond metathesis with
      increasing O-content, as active sites evolve from metal atom pairs (*-*) to
      oxygen atom (O*-O*) pairs and ultimately to Pd cation-lattice oxygen pairs
      (Pd(2+)-O(2-)) in PdO. The charges in the CH3 and H moieties along the reaction
      coordinate depend on the accessibility and chemical state of the Pd and O centers
      involved. Homolytic C-H dissociation prevails on bare (*-*) and O*-covered
      surfaces (O*-O*), while C-H bonds cleave heterolytically on Pd(2+)-O(2-) pairs at
      PdO surfaces. On bare surfaces, C-H bonds cleave via oxidative addition,
      involving Pd atom insertion into the C-H bond with electron backdonation from Pd
      to C-H antibonding states and the formation of tight three-center
      (H3C...Pd...H)(?) transition states. On O*-saturated Pd surfaces, C-H bonds
      cleave homolytically on O*-O* pairs to form radical-like CH3 species and nearly
      formed O-H bonds at a transition state (O*...CH3(*)...*OH)(?) that is looser and
      higher in enthalpy than on bare Pd surfaces. On PdO surfaces, site pairs
      consisting of exposed Pd(2+) and vicinal O(2-), Pd(ox)-O(ox), cleave C-H bonds
      heterolytically via sigma-bond metathesis, with Pd(2+) adding to the C-H bond,
      while O(2-) abstracts the H-atom to form a four-center (H3C(delta
      )...Pd(ox)...H(delta+)...O(ox))(?) transition state without detectable Pd(ox)
      reduction. The latter is much more stable than transition states on *-* and O*-O*
      pairs and give rise to a large increase in CH4 oxidation turnover rates at oxygen
      chemical potentials leading to Pd to PdO transitions. These distinct mechanistic
      pathways for C-H bond activation, inferred from theory and experiment, resemble
      those prevalent on organometallic complexes. Metal centers present on surfaces as
      well as in homogeneous complexes act as both nucleophile and electrophile in
      oxidative additions, ligands (e.g., O* on surfaces) abstract H-atoms via
      reductive deprotonation of C-H bonds, and metal-ligand pairs, with the pair as
      electrophile and the metal as nucleophile, mediate sigma-bond metathesis
      pathways.

PMID- 24083570
TI  - Bactericidal activity of PA-824 against Mycobacterium tuberculosis under
      anaerobic conditions and computational analysis of its novel analogues against
      mutant Ddn receptor.
AB  - BACKGROUND: The resurgence of multi-drug resistant tuberculosis (MDR-TB) and HIV
      associated tuberculosis (TB) are of serious global concern. To contain this
      situation, new anti-tuberculosis drugs and reduced treatment regimens are
      imperative. Recently, a nitroimidazole, PA-824, has been shown to be active
      against both replicating and non-replicating bacteria. It is activated by the
      enzyme Deazaflavin-dependent nitroreductase (Ddn) present in Mycobacterium
      tuberculosis which catalyzes the reduction of PA-824, resulting in the release of
      lethal reactive nitrogen species (RNS) within the bacteria. In this context, PA
      824 was analyzed for its activity against latent tuberculosis under anaerobic
      conditions and compared with rifampicin (RIF) and pyrazinamide (PZA). Recent
      mutagenesis studies have identified A76E mutation which affects the above
      mentioned catalysis and leads to PA-824 resistance. Hence, novel analogues which
      could cope up with their binding to mutant Ddn receptor were also identified
      through this study. RESULTS: PA-824 at an optimum concentration of 12.5 MUg/ml
      showed enhanced bactericidal activity, resulting in 0 CFU/ml growth when compared
      to RIF and PZA at normal pH and anaerobic condition. Further docking studies
      revealed that a combinatorial structure of PA-824 conjugated with moxifloxacin
      (ligand 8) has the highest binding affinity with the wild type and mutant Ddn
      receptor. CONCLUSIONS: PA-824 has been demonstrated to have better activity under
      anaerobic condition at 12.5 MUg/ml, indicating an optimized dose that is required
      for overcoming the detoxifying mechanisms of M. tuberculosis and inducing its
      death. Further, the development of resistance through A76E mutation could be
      overcome through the in silico evolved ligand 8.

PMID- 24083573
TI  - Solvothermal annealing of block copolymer thin films.
AB  - A two-stage annealing process for block copolymer films was introduced consisting
      of a solvent vapor exposure followed by a thermal cycle. By heating the film but
      not the chamber, changes in the ambient vapor pressure of the solvent were
      avoided. Films of block copolymers and homopolymers showed transient nonmonotonic
      swelling behavior immediately after solvent exposure that was dependent on how
      the thin film was cast before the anneal. Thermal cycling of the solvent-swelled
      block copolymer films during the solvent vapor anneal (SVA) caused the films to
      deswell in 1-10 s and produced well-ordered microdomains in templated 45.5 and
      51.5 kg/mol polystyrene-block-polydimethylsiloxane films annealed in toluene and
      n-heptane vapors for total process times of 30 s to 5 min. 

PMID- 24083572
TI  - A retrospective study: the prognostic value of anemia, smoking and drinking in
      esophageal squamous cell carcinoma with primary radiotherapy.
AB  - BACKGROUND: Few studies have investigated the relationship between anemia,
      smoking, drinking and survival in esophageal squamous cell carcinoma (ESCC) with
      primary radiotherapy. This study had the aim of evaluating the prognostic value
      of anemia, smoking and drinking in patients receiving primary radiotherapy for
      ESCC. METHODS: A total of 79 patients who underwent radiotherapy during initial
      treatment for ESCC were included in this study. The 2-year overall survival (OS)
      and disease-free survival (DFS) were analyzed between the anemic and non-anemic
      groups, non-smokers and smokers, and non-drinkers and drinkers using the Kaplan
      Meier method and the Cox proportional hazards model. RESULTS: There were 79
      patients (10 male) of median age 63 (range 38 to 84) years. The 2-year OS and DFS
      were 36% and 25%, respectively, in the non-anemic group, and 17% and 13%,
      respectively, in the anemic group (P = 0.019 for OS; P = 0.029 for DFS) using the
      Kaplan-Meier method. Survival analysis using the Kaplan-Meier method showed that
      the 2-year OS and DFS had no statistical difference between smoking, drinking and
      survival. In a univariate analysis, anemia was identified as a significant
      prognostic factor for 2-year OS (hazard ratio (HR) = 1.897; P = 0.024) and 2-year
      DFS (HR = 1.776; P = 0.036), independent of tumor, lymph node, metastasis (TNM)
      stage. In a multivariate analysis, anemia was identified as a highly significant
      prognostic factor for 2-year OS (HR = 2.125; P = 0.011) and 2-year DFS (HR =
      1.898; P = 0.025), independent of TNM stage and initial treatment. We found no
      statistical difference in the 2-year OS and DFS associated with smoking (P > 0.2)
      and drinking (P > 0.6) using univariate and multivariate analysis. CONCLUSIONS:
      Smoking and drinking were not prognostic for 2-year OS or DFS. Anemia before
      radiotherapy was associated with poor prognosis and an increased risk of relapse,
      which may serve as a new prognostic characteristic in ESCC treated with primary
      radiotherapy. Hemoglobin is a routine examination and anemia is therefore simple
      and quick to determine.

PMID- 24083574
TI  - Aggregation kinetics of SERS-active nanoparticles in thermally stirred sessile
      droplets.
AB  - The aggregation kinetics of silver nanoparticles in sessile droplets were
      investigated both experimentally and through numerical simulations as a function
      of temperature gradient and evaporation rate, in order to determine the
      hydrodynamic and aggregation parameters that lead to optimal surface-enhanced
      Raman spectroscopic (SERS) detection. Thermal gradients promote effective
      stirring within the droplet. The aggregation reaction ceases when the solvent
      evaporates forming a circular stain consisting of a high concentration of silver
      nanoparticle aggregates, which can be interrogated by SERS leading to analyte
      detection and identification. We introduce the aggregation parameter, Gammaa =
      tau(evap)/tau(a), which is the ratio of the evaporation to the aggregation time
      scales. For a well-stirred droplet, the optimal condition for SERS detection was
      found to be Gamma(a,opt) = kc(NP)tau(evap) ~ 0.3, which is a product of the
      dimerization rate constant (k), the concentration of nanoparticles (cNP), and the
      droplet evaporation time (tau(evap)). Near maximal signal (over 50% of maximum
      value) is observed over a wide range of aggregation parameters 0.05 < Gammaa <
      1.25, which also defines the time window during which trace analytes can be
      easily measured. The results of the simulation were in very good agreement with
      experimentally acquired SERS spectra using gas-phase 1,4-benzenedithiol as a
      model analyte.

PMID- 24083575
TI  - The cysteine protease cathepsin B is a key drug target and cysteine protease
      inhibitors are potential therapeutics for traumatic brain injury.
AB  - There are currently no effective therapeutic agents for traumatic brain injury
      (TBI), but drug treatments for TBI can be developed by validation of new drug
      targets and demonstration that compounds directed to such targets are efficacious
      in TBI animal models using a clinically relevant route of drug administration.
      The cysteine protease, cathepsin B, has been implicated in mediating TBI, but it
      has not been validated by gene knockout (KO) studies. Therefore, this
      investigation evaluated mice with deletion of the cathepsin B gene receiving
      controlled cortical impact TBI trauma. Results indicated that KO of the cathepsin
      B gene resulted in amelioration of TBI, shown by significant improvement in motor
      dysfunction, reduced brain lesion volume, greater neuronal density in brain, and
      lack of increased proapoptotic Bax levels. Notably, oral administration of the
      small-molecule cysteine protease inhibitor, E64d, immediately after TBI resulted
      in recovery of TBI-mediated motor dysfunction and reduced the increase in
      cathepsin B activity induced by TBI. E64d outcomes were as effective as cathepsin
      B gene deletion for improving TBI. E64d treatment was effective even when
      administered 8 h after injury, indicating a clinically plausible time period for
      acute therapeutic intervention. These data demonstrate that a cysteine protease
      inhibitor can be orally efficacious in a TBI animal model when administered at a
      clinically relevant time point post-trauma, and that E64d-mediated improvement of
      TBI is primarily the result of inhibition of cathepsin B activity. These results
      validate cathepsin B as a new TBI therapeutic target.

PMID- 24083576
TI  - Identification of biomarkers for hepatocellular carcinoma using network-based
      bioinformatics methods.
AB  - BACKGROUND: Hepatocellular carcinoma (HCC) is one of the most common types of
      cancer worldwide. Despite several efforts to elucidate molecular mechanisms
      involved in this cancer, they are still not fully understood. METHODS: To acquire
      further insights into the molecular mechanisms of HCC, and to identify biomarkers
      for early diagnosis of HCC, we downloaded the gene expression profile on HCC with
      non-cancerous liver controls from the Gene Expression Omnibus (GEO) and analyzed
      these data using a combined bioinformatics approach. RESULTS: The dysregulated
      pathways and protein-protein interaction (PPI) network, including hub nodes that
      distinguished HCCs from non-cancerous liver controls, were identified. In total,
      29 phenotype-related differentially expressed genes were included in the PPI
      network. Hierarchical clustering showed that the gene expression profile of these
      29 genes was able to differentiate HCC samples from non-cancerous liver samples.
      Among these genes, CDC2 (Cell division control protein 2 homolog), MMP2 (matrix
      metalloproteinase-2) and DCN (Decorin were the hub nodes in the PPI network.
      CONCLUSIONS: This study provides a portfolio of targets useful for future
      investigation. However, experimental studies should be conducted to verify our
      findings.

PMID- 24083577
TI  - Anthelmintic activity of Securidaca longepedunculata (Family: Polygalaceae) root
      extract in mice, in vitro and in vivo.
AB  - OBJECTIVE: To elucidate the pharmacological bases of oral administration of
      Securidaca longepedunculata (S. longepedunculata) root extract as an anthelmintic
      in folkloric medicine. METHODS: Albino mice were infected with infective third
      (L3) larval stage of Heligmosomoides polygyrus (H. polygyrus) by esophageal
      intubation. Following establishment of the adult worms in the intestine, the mice
      were treated with 0-2 000 mg/kg body weight (bw) of methanolic root extract of S.
      longepedunculata and 100 mg/kg bw of pyrantel embonate, the reference drug in
      vivo. Bioactivity and larvicidal effects of the extract were tested by exposing
      brine shrimps (Artemia salina) to 0.00-1.00 mg/mL and the L3 stage of
      Heligmosomoidescontortus (H. contortus) and H. polygyrus to 0.00-2.50 mg/mL of
      the extract in vitro. RESULTS: The percentage yield of the extract was 7.13% w/w
      dry matter. The brine shrimps toxicity bioassay resulted in an LC50 of 74.18
      MUg/mL. The extract had a significant, dose-dependent larvicidal effect on the L3
      stage of H. contortus and H. polygyrus with the terminal effect of 75% and 70% at
      the highest exposure concentrations, respectively. The extract however, did not
      affect the number of worm eggs per gram (epg) of fecal materials (P<0.05) and
      total worm burden (twb) of adult H. polygyrus in infected mice. Treatment with
      pyrantel embonate significant reduced both the fecal egg count and twb to 0
      compared to the untreated control (P<0.05). CONCLUSIONS: These results indicate
      that S. longepedunculata root extract contains potent bioactive compounds and has
      larvicidal effect on L3 stage of H. contortus and H. polygyrus, substantiating
      its use as anthelmintic in alternative medicine.

PMID- 24083578
TI  - Larvicidal efficacy of Catharanthus roseus Linn. (Family: Apocynaceae) leaf
      extract and bacterial insecticide Bacillus thuringiensis against Anopheles
      stephensi Liston.
AB  - OBJECTIVE: To explore the larvicidal activity of Catharanthus roseus (C. roseus)
      leaf extract and Bacillus thuringiensis (B. thuringiensis) against the malarial
      vector Anopheles stephensi (An. stephensi), when being used alone or together.
      METHODS: The larvicidal activity was assayed at various concentrations under the
      laboratory and field conditions. The LC50 and LC90 values of the C. roseus leaf
      extract were determined by probit analysis. RESULTS: The plant extract showed
      larvicidal effects after 24 h of exposure; however, the highest larval mortality
      was found in the petroleum ether extract of C. roseus against the first to fourth
      instars larvae with LC50=3.34, 4.48, 5.90 and 8.17 g/L, respectively; B.
      thuringiensis against the first to fourth instars larvae with LC50=1.72, 1.93,
      2.17 and 2.42 g/L, respectively; and the combined treatment with LC50=2.18, 2.41,
      2.76 and 3.22 g/L, respectively. No mortality was observed in the control.
      CONCLUSIONS: The petroleum ether extract of C. roseus extract and B.
      thuringiensis have potential to be used as ideal eco-friendly agents for the
      control of An. stephensi in vector control programs. The combined treatment with
      this plant crude extract and bacterial toxin has better larvicidal efficacy
      against An. stephensi.

PMID- 24083579
TI  - Mosquitocidal properties of Solanum trilobatum L. (Solanaceae) leaf extracts
      against three important human vector mosquitoes (Diptera: Culicidae).
AB  - OBJECTIVE: To determine the larvicidal and pupicidal activites of Solanum
      trilobatum (S. trilobatum) leaf extracts against Aedes aegypti (Ae. aegypti),
      Culex quinquefasciatus (Cx. quinquefasciatus) and Anopheles stephensi (An.
      stephensi). METHODS: The larvicidal and pupucidal was determined at five
      different concentrations of 50, 100, 150, 200 and 250 ppm. Percentage of larval
      mortality was assessed after 48 h. RESULTS: Methanol extracts of S. trilobatum
      was found to be more susceptible against the larvae of Ae. aegypti, Cx.
      quinquefasciatus and An. stephensi at 250 ppm with a LC50 value of 125.43, 127.77
      and 116.64 ppm respectively. Leaf methanol extracts of S. trilobatum also
      exhibited pupicidal and adult emergence properties. CONCLUSIONS: These results
      suggested that the leaf extracts of S. trilobatum showed potential to be used as
      an ideal ecofriendly approach for the control of the Ae. Aegypti, Cx.
      quinquefasciatus and An. stephensi.

PMID- 24083580
TI  - Assessment of anti mosquito measures in households and resistance status of Culex
      species in urban areas in southern Ghana: implications for the sustainability of
      ITN use.
AB  - OBJECTIVE: To determine resistance status of Culex species to different class of
      insecticides and assess the major anti-mosquito strategies employed by urban
      households and their possible effects on malaria acquisition. METHODS: Structured
      questionnaires were randomly administered to obtain information on demographic
      characteristics, measures that people use to prevent mosquito bites and their
      perception of where mosquitoes breed in their communities. Adult susceptibility
      assays were also carried out using WHO discriminating dosages of four
      insecticides from different chemical classes against Culex species. RESULTS:
      Majority of respondents (54.75%) preferred the use of domestic insecticides in
      the form of aerosols and coils. Among households that used domestic insecticides,
      the use of coil was most frequent (62.9%) with a mean (95% CI) of 9.18 (8.99,
      9.37) coils per week. Strong level of pyrethroid-resistance and multiple
      insecticide resistance in Culex species were also detected in some of the study
      sites. CONCLUSIONS: The excessive use of domestic insecticides and high level of
      resistance in Culex species observed in the study area has implications for the
      ITN component of the nation's malaria control program in more subtle ways. People
      will lose interest in the use of ITN when it fails to protect users from bites of
      resistant Culex species. Excessive use of domestic insecticides may also select
      resistance in both malaria vectors and Culex species. On this account we
      recommend that nuisance mosquitoes must be controlled as part of malaria control
      programs to improve acceptance and utilization of ITN.

PMID- 24083581
TI  - Malaria prevalence in north-eastern Nigeria: a cross-sectional study.
AB  - OBJECTIVE: To assess the prevalence of malaria parasitemia in north-east Nigeria
      and to evaluate the measures for the prevention of malaria. METHODS: A village in
      north-eastern Nigeria was selected for the cross sectional study at the height of
      the rainy season in October 2011. A total of 550 inhabitants of a hamlet were
      recruited for this study. After obtaining the consent individuals received a
      structured interview and were tested for malaria parasites in their blood films.
      Recruits testing positive for malaria were given a course of artemesinin-based
      combination therapy (ACT). RESULTS: A total of 497 inhabitants representing
      approximately 90 percent of the population participated: a quarter of the study
      group carried malaria parasitesexclusively Plasmodium falciparum(P. falciparum)
      representing a P. falciparum parasite rate (PfPR) of 24.5%. Besides, 53/138 in
      the age group of 2 to < 10 years old children tested positive for P. falciparum
      representing a PfPR2-10 value of 38.4%. Malaria control measures were used in
      just under a third (157/497) of this cohort. Despite these measures 28/157
      (17.8%) still tested positive for P. falciparum. CONCLUSIONS: The malaria burden
      is overestimated for this region in north-east Nigeria. The findings support an
      intermediate pattern of malaria endemicity. The 30% bed nets coverage for malaria
      control is well below the WHO estimates for 2011.

PMID- 24083582
TI  - Central nervous system activity of Illicium verum fruit extracts.
AB  - OBJECTIVE: To research the acute toxicity of Illicium verum (I. verum) fruit
      extracts and its action on central nervous system. METHODS: The TLC and HPTLC
      techniques were used as fingerprints to determine the chemical components present
      in I. verum. Male albino rats and mice were utilized for study. The powdered
      material was successively extracted with n-hexane, ethyl acetate and methanol
      using a Soxhlet extractor. Acute toxicity studies were performed as per OECD
      guidelines. The CNS activity was evaluated on parameters of general behavior,
      sleeping pattern, locomotor activity, anxiety and myocoordination activity. The
      animals were trained for seven days prior to experiments and the divided into
      five groups with six animals in each. The drug was administered by
      intraperitoneal route according to body weight. The dosing was done as prescribed
      in each protocol. RESULTS: Toxicity studies reported 2 000 mg/kg as toxicological
      dose and 1/10 of the same dose was taken as therapeutic dose Intraperitoneal
      injection of all extracts at dose of 200 mg prolonged phenobarbitone induced
      sleeping time, produced alteration in general behavior pattern, reduced locomotor
      activity and produced anxiolytic effects but the extracts do not significantly
      alter muscles coordination activity. The three extracts of I. verum at the dose
      of 200 mg, methanol extract was found to produce more prominent effects, then
      hexane and ethylacetate extracts. CONCLUSIONS: The observation suggested that the
      extracts of I. verum possess potent CNS depressant action and anxiolytic effect
      without interfering with motor coordination.

PMID- 24083583
TI  - Isolation and characterization of halophilic Bacillus sp. BS3 able to produce
      pharmacologically important biosurfactants.
AB  - OBJECTIVE: To characterize the pharmacological importance of biosurfactants
      isolated from halophilic Bacillus sp BS3. METHODS: Halophilic Bacillus sp. BS3
      was isolated from solar salt works, identified by 16S rRNA sequencing and was
      used for screening their biosurfactant production. Characters of the
      biosurfactant and their anticancer activity were analyzed and performed in
      mammary epithelial carcinoma cell at different concentrations. RESULTS: The
      biosurfactant were characterized by TLC, FTIR and GC-MS analysis and identified
      as lipopeptide type. GC-MS analysis revealed that, the biosurfactant had various
      compounds including 13-Docosenamide, (Z); Mannosamine, 9- and N,N,N',N'
      tetramethyl. Surprisingly the antiviral activity was found against shrimp white
      spot syndrome virus (WSSV) by suppressing the viral replication and significantly
      raised shrimp survival (P<0.01). Anticancer activity performed in the mammary
      epithelial carcinoma cell at different concentrations of biosurfactants, among
      the various concentrations of biosurfactants such as 0.000 25, 0.002 5, 0.025,
      0.25 and 2.5 MUg, the 0.25 MUg concentration suppressed the cells significantly
      (P<0.05) to 24.8%. CONCLUSIONS: Based on the findings, the present study
      concluded that, there is a possibility to develop eco-friendly antimicrobial and
      anticancer drugs from the extremophilic origin.

PMID- 24083584
TI  - Effect of rhBMP-2 sustained-release nanocapsules on the ectopic osteogenesis
      process in Sprague-Dawley rats.
AB  - OBJECTIVE: To explore the effect of sustained-release recombinant human bone
      morphogenetic protein-2 (rhBMP-2) on ectopic osteogenesis in the muscle pouches
      of rats through preparing rhBMP-2 sustained-release capsules by wrapping
      morphogenesis protein bones-2 (BMP-2) using chitosan nanoparticles, and
      compositing collagen materials. METHODS: Twenty four Sprague-Dawley rats were
      randomly divided into four groups with six rats in each group, that is Group A
      (control group), Group B (only treated with collagen), Group C (rhBMP-2+collagen
      treated group) and Group D (rhBMP-2/cs+collagen treated group). The composite
      materials for each group were implanted in the bilateral peroneal muscle pouches
      in rats. The peroneal muscles were only separated without implanting any
      materials in control group. Rats were sacrificed 2 weeks and 4 weeks post
      treatment and samples were cut off for general observation, Micro CT scans and
      histological observation. RESULTS: General observation showed no new bone
      formation in Groups A and B mice, while new bones were formed in Groups C and D
      mice. Two weeks after treatment Micro CT scans showed that The bone volume
      fraction (BVF), trabecular thickness (Tb.Th), bone mineral density (BMD) in Group
      C mice were all higher than that in Group D (P<0.05). At the fourth week, the
      BVF, Tb.Th and BMD were significantly higher than that at the second week
      (P<0.01). CONCLUSIONS: The slow-release effect of rhBMP-2/cs sustained-release
      capsules can significantly promote ectopic osteogenesis. Its bone formation
      effect is better than that of rhBMP-2 burst-release group.

PMID- 24083585
TI  - Effect of intestinal function-recovering decoction on treatment of multiple organ
      dysfunction syndrome in rats.
AB  - OBJECTIVE: To analyze the effect of intestinal function-recovering decoction on
      multiple organ dysfunction syndrome in rats, and to investigate a novel solution
      to multiple organ dysfunction syndrome. METHODS: Multiple organ dysfunction
      syndrome was induced in 60 Sprague-Dawley rats by intestinal ischemia-reperfusion
      combined with cecal ligation and puncture. Then these rats were intragastrically
      administered physiological saline (group I, n=20), ampicillin (group II, n=20) or
      intestinal function-recovering decoction (group III, n=20). After treatment,
      serum malondialdehyde and superoxide dismutase levels were compared among three
      groups. Simultaneously, bacterial culture of various organ tissues was performed
      and bacterial and endotoxin translocation were observed. RESULTS: Compared with
      group I, serum malondialdehyde, alanine aminotransferase and aspartate
      aminotransferase levels were significantly decreased (all P<0.05) and serum
      superoxide dismutase level was significantly increased (P<0.05) in the group III.
      However, there were no significant differences in these indices between groups II
      and III (P>0.05). The rate of bacterial translocation in the groups II and III
      was significantly lower than in the group I (P<0.05), and no significant
      difference was observed between groups II and III (P>0.05). CONCLUSIONS:
      Intestinal function-recovering decoction can significantly reduce endotoxin and
      bacterial translocation and stabilize enteral oxidative-antioxidative balance.

PMID- 24083586
TI  - Construction of the tissue engineering seed cell (HaCaT-EGF) and analysis of its
      biological characteristics.
AB  - OBJECTIVE: To construct the tissue engineering seed cell (HaCaT cell line) with
      stable expression of the human epidermal growth factor (EGF), and analyze the
      changes of its biological characteristics. METHODS: PCDNA3.1-EGF eukaryotic
      expression vector was transferred into HaCaT cell, and G418 was utilized to
      select the HaCaT-EGF cell line. Using an inverted microscope, PCR, ELISA method
      to detect the changes of the cell morphology, the expression of the EGF gene and
      protein, and the mRNA expression levels of apoptosis related molecule Caspase-3,
      the cell cycle related protein cyclin D1. RESULTS: The mRNA expression levels of
      the obtained HaCaT-EGF cell were more than 100 times higher than the level of
      ordinary HaCaT cell. The colony of the HaCaT-EGF cells was more focused and tight
      compared to the empty vector transfected HaCaT cells and normal HaCaT cells. The
      expression levels of apoptotic factor Caspase-3 and cyclin D1 in HaCaT-EGF cell
      were significantly higher than those in the empty vector HaCaT- pcDNA3.1 cell,
      and the differences were statistically significant (P<0.01), but there was no
      significant difference compared to the normal HaCaT cells (P>0.05). CONCLUSIONS:
      HaCaT-EGF cell can continuously secrete EGF, and the biological characteristic is
      stable. It can be used for tissue engineering experiment and is an ideal seed
      cell for constructing tissue engineered skin.

PMID- 24083587
TI  - Change of hs-CRP, sVCAM-1, NT-proBNP levels in patients with pregnancy-induced
      hypertension after therapy with magnesium sulfate and nifedipine.
AB  - OBJECTIVE: To investigate the change of the hs-CRP, sVCAM-1, NT-proBNP levels of
      the patients with pregnancy-induced hypertension (PIH) syndrome. METHODS: A total
      of 200 patients with PIH were divided into mild, moderate and severe group, and
      50 healthy pregnancy patients served as the control group. The serum sVCAM-1
      levels were detected by enzyme-linked immunosorbent assay, hs-CRP were detected
      by immunity transmission turbidity, and NT-proBNP levels were determined by the
      colloidal gold method. Patients were treated with magnesium sulfate and
      nifedipine and the contrastive analysis was performed before and after treatment.
      And the pathological changes in placental of PIH patients were detected by
      hematoxylin-eosin staining at the same time. RESULTS: The hs-CRP, sVCAM-1, NT
      proBNP levels of patients in the mild, moderate and severe PIH group were
      significantly higher than that in the control group (P<0.05). The hs-CRP, sVCAM
      1, NT-proBNP levels in the severe group were significantly higher than the mild
      group and the moderate group, the difference was statistically significant
      (P<0.05). The hs-CRP, sVCAM-1, NT-proBNP of the moderate group were significantly
      higher than the mild group (P<0.05). There was a positive correlation between hs
      CRP, sVCAM-1, NT-proBNP expression levels and the degree of the PIH. The
      expression of hs-CRP, sVCAM-1, NT-proBNP levels of the moderate and the severe
      group were significantly decreased (P<0.05). The number of placental villi and
      interstitial blood vessel in the moderate and severe PIH group were significantly
      less than the control group (P<0.05). CONCLUSIONS: The increased levels of serum
      hs-CRP, sVCAM-1, NT-proBNP may be involved in the process of vascular endothelial
      cell injury of the PIH, and the hs-CRP, sVCAM-1, NT-proBNP can be used as the
      auxiliary index for diagnosis of PIH and determination of PIH severity.

PMID- 24083588
TI  - Application of internal fixation of steel-wire limited loop in early Achilles
      tendon rupture.
AB  - OBJECTIVE: To explore the clinical effect and safety of internal fixation of
      steel-wire limited loop in early Achilles tendon rupture. METHODS: Seventy-six
      patients respectively with early transected and avulsed types of Achilles tendon
      rupture were selected and treated with internal fixation of steel-wire limited
      loop. The patients began to take exercise for their lower limbs through continous
      passive motion as early as possible after surgical repair, and the loops were
      removed after 3-5 months. Six months later, the condition of complications
      including Achilles tendon re-rupture, wound fistula, wound infection and skin
      necrosis, cutaneous sensation in sural nerve dominance region, time back to
      preinjury work or learning as well as time to physical activities were observed.
      One year later, the therapeutic effect was evaluated, and the maximum
      circumferences of bilateral legs and ruptured plane circumferences of Achilles
      tendon were measured. RESULTS: The wound of all patients healed well, no
      complications like Achilles tendon re-rupture, wound fistula, wound infection and
      skin necrosis occured, and the cutaneous sensation in sural nerve dominance
      region was normal. The mean time back to preinjury work or learning as well as to
      pysical activities of all patients were respectively 10 and 22 weeks. Seventy out
      of 76 patients (92.1%) achieved an excellent effect, and 6 (7.9%) good effect.
      The excellent and good rate came up to 100%. The maximum circumference in the
      affected leg decreased to 2 mm averagely compared with the offside, while the
      ruptured plane circumferences of Achilles tendon in the affected side increased
      to 2.2 mm compared with the offside. CONCLUSIONS: For early Achilles tendon
      rupture, internal fixation of steel-wire limited loop can recover the ankle
      function better, return to the preinjury state in the shortest time, and has few
      complications.

PMID- 24083589
TI  - Expression of hENTl and ERCC1 genes in tumor tissues non-small cell lung cancer.
AB  - OBJECTIVE: To investigate the expression of hENTl and ERCC1 genes in tumor
      tissues non-small cell lung cancer (NSCLC). METHODS: Fresh non-small lung cancer
      specimens were transplanted into nude mice. Twenty mice were randomized into two
      groups: experimental group receiving gemcitabine plus cisplatin and control group
      receiving 0.9% physiological saline. The expressions of hENTl and ERCC1 mRNA in
      tumor tissue were detected by real-time fluorescent quantitative PCR. The volume
      of tumor, the weight of nude mice and tumor volume were respectively measured and
      calculated 2-3 times per week. Tissue samples were collected from NSCLC mice
      treated with gemcitabine plus carboplatin. RESULTS: The histological examination
      showed that many tumor cells were well preserved in nude mice. The rate of
      transplanted tumor cells was 86.7%. The concomitant treatment study showed that
      the rate of TV, RTV, T/C in GEM + DDP group was the lowest. LBP + DOC, DDP + DOC
      obviously influenced the body weight. Compared with NS group, DDP group, GEM
      group, the survival period and the level of hENTl of DDP+GEM group increased
      obviously, the level of ERCC1 decreased significantly (P<0.05). CONCLUSIONS: The
      expression of hENT1 and ERCC1 genes in tumor tissues were closely correlated with
      the response to chemotherapy and prognosis of patients with NSCLC treated with
      gemcitabine plus cisplatin.

PMID- 24083590
TI  - Safety of polyethylene glycol recombinant human granulocyte colony-stimulating
      factor in treating non-small cell lung cancer patients at I b stage.
AB  - OBJECTIVE: To investigate resistance and safety of HHPG-19K in treating non-small
      cell lung cancer patients. METHODS: A total of 30 cases were selected and
      randomly divided into 5 groups: three HHPG-19K groups of different dosage (60
      MUg/kg/day, 100 MUg/kg/day, 200 MUg/kg/day), positive control group (Filgrastim,
      namely G-CSF5 MUg/kg/day) and negative control group. Safety indexes of 5 groups
      were observed and compared. RESULTS: All patients had adverse event (100%) in
      three HHPG-19K groups, and increased ALP, ALT and AST were main events. The
      degree was mild to moderate. There was no significant difference in the incidence
      of adverse event between dosage groups and positive control group no difference.
      But the incidence of negative control group was 13%, which was significantly
      lower than dosage groups and positive control group. CONCLUSIONS: non-small cell
      lung cancer patients have satisfactory tolerance to HHPG-19K, and have no
      resistance. Besides, dosage at 100 MU g/kg is the most safe.

PMID- 24083591
TI  - Relation between K469E gene polymorphism of ICAM-1 and recurrence of ACS and
      cardiovascular mortality.
AB  - OBJECTIVE: To explore the relation between K469E gene polymorphism of
      intercellular adhesion molecular-1 (ICAM-1) and the recurrence of ACS and
      cardiovascular mortality. METHODS: A total of 185 patients with ACS hospitalized
      in Department of Cardiology in our hospital from Sep 2007 to Sep 2008 were
      selected as objectives. Polymerase chain reaction was used to analyze K469E gene
      polymorphism of ICAM-1. According to the genotypes, they were divided into two
      groups: group with K allele (KK+KE) and group without K allele (EE). The two
      groups were followed up prospectively for five years and blood lipid, blood
      pressure, blood glucose, recurrence and death of ACS were collected when the
      patients left hospital. The relation between ICAM-1 gene polymorphism and the
      recurrence of ACS and cardiovascular mortality was analyzed by Logistic
      regression. RESULTS: After long-term follow-up, it was found that ACS recurred on
      71 cases (38.4%) and 10 cases died, among which 3 cases died of cardiovascular
      disease. The recurrence of ACS and cardiovascular mortality in group with K
      allele were remarkably higher than that in group without K allele (P<0.01). After
      multivariate Logistic regression adjusted ages, gender, weight indexes, TC, LDL
      C, TG, smoking, drinking, family history of cardiovascular disease, history of
      hypertension and the severity of coronary artery disease, the risks of ACS
      recurrence and cardiovascular mortality in group with genotype KK+KE was 3.31 and
      3.53 times of those in group with genotype EE respectively (P<0.01). When the
      independent variable of hypertension was introduced in regression analysis, the
      risks of ACS recurrence and cardiovascular mortality in group with K allele both
      decreased (P<0.05). When the independent variable of HDL-C was introduced,
      different genotypes of ICAM-1 weren't relevant with ACS recurrence and
      cardiovascular mortality (P>0.05). CONCLUSIONS: K469E gene polymorphism of ICAM-1
      was related to ACS recurrence and cardiovascular mortality, K allele probably an
      independent risky factor and hypertension and to which the level of HDL-C were
      closely related.

PMID- 24083592
TI  - In vitro drug resistance of clinical isolated Brucella against antimicrobial
      agents.
AB  - OBJECTIVE: To explore the antibiotic resistance of Brucella melitensis and
      instruct rational use of antimicrobial agents in clinical treatment of Brucella
      infection. METHODS: Bacteria were cultured and identified by BACTEC9120 and VITEK
      II automicrobic system. E-test was used to detect the minimal inhibitory
      concentration (MIC) of antimicrobial agents in the drug susceptivity experiment.
      RESULTS: A total of 19 brucella strains (all Brucella melitensis) were isolated
      from 19 patients, who had fever between January 2010 and June 2012, and 17
      samples were blood, one was bone marrow, the other sample was cerebrospinal
      fluid. The MIC range of ceftazidime was 2.0-8.0 mg/L, rifampicin was 0.06-2.0
      mg/L, amikacin was 4.0-12.0 mg/L, levofloxacin was 2.0-8.0 mg/L, doxycycline was
      8.0-32.0 mg/L, sulfamethoxazole-trimethoprim was 4.0-16.0 mg/L, ampicillin was
      1.5-2.0 mg/L and gentamicin was 0.50-0.75 mg/L. CONCLUSIONS: The drugs used in
      this experiment cover common drugs for treating Brucella. Meanwhile, the results
      are consistent with clinical efficacy. It is suggested personalized regimen
      according to patients' status in treatment of Brucella.

PMID- 24083594
TI  - The frontline treatment of chronic myeloid leukemia in the chronic phase: current
      clinical decisions and future prospects for treatment.
AB  - The use of tyrosine kinase inhibitors (TKIs) has revolutionized the treatment of
      chronic myeloid leukemia (CML). For patient with chronic phase CML, frontline
      treatment with imatinib leads to an estimated event-free survival and overall
      survival at 8 years of 81 and 85%, respectively. Second-generation TKIs
      (dasatinib and nilotinib) have shown improved early cytogenetic and molecular end
      points compared with imatinib in frontline randomized studies. Imatinib,
      dasatinib and nilotinib are all now approved for the frontline therapy. Overall
      treatment success is dependent in large part on treatment compliance, effective
      management of side effects of the therapy and close monitoring and achievement of
      cytogenetic and molecular milestones. 

PMID- 24083593
TI  - Association between treatment or usual care region and hospitalization for fall
      related traumatic brain injury in the Connecticut Collaboration for Fall
      Prevention.
AB  - OBJECTIVES: To evaluate the association between the treatment region (TR) or
      usual care region (UCR) of the Connecticut Collaboration for Fall Prevention
      (CCFP), a clinical intervention for prevention of falls, and the rate of
      hospitalization for fall-related traumatic brain injury (FR-TBI) in persons aged
      70 and older and to describe the Medicare charges for FR-TBI hospitalizations.
      DESIGN: Using a quasi-experimental design, rates of hospitalization for FR-TBI
      were recorded over an 8-year period (2000-2007) in two distinct geographic
      regions (TR and UCR) chosen for their similarity in characteristics associated
      with occurrence of falls. SETTING: Two geographical regions in Connecticut.
      PARTICIPANTS: More than 200,000 persons aged 70 and older. INTERVENTION:
      Clinicians in the TR translated research protocols from the Yale Frailty and
      Injuries: Cooperative Studies of Intervention Techniques, a successful fall
      prevention randomized clinical trial, into discipline- and site-specific fall
      prevention procedures for integration into their clinical practices.
      MEASUREMENTS: Rate of hospitalization for FR-TBI in persons aged 70 and older.
      RESULTS: Connecticut Collaboration for Fall Prevention's TR exhibited lower rates
      of hospitalization for FR-TBI than the UCR (risk ratio = 0.84, 95% credible
      interval = 0.72-0.99). CONCLUSION: The significantly lower rate of
      hospitalization for FR-TBI in CCFP's TR suggests that the engagement of
      practicing clinicians in the implementation of evidence-based fall-prevention
      practices may reduce hospitalizations for FR-TBI.

PMID- 24083595
TI  - Mortality salience biases attention to positive versus negative images among
      individuals higher in trait self-control.
AB  - Death is inevitable. One way people cope with awareness of death is to focus on
      the positive things in life. Consistent with this idea, reminders of personal
      mortality have been found to increase optimism and tune attention towards
      positive information. The current research tested the hypothesis that persons
      higher in trait self-control are especially likely to attend to positive (versus
      negative) stimuli under mortality salience (MS). Participants completed a measure
      of trait self-control, contemplated their own mortality or a control topic, and
      then viewed positive and negative affective images while their gaze patterns were
      recorded. MS increased the attention to positive (versus negative) images among
      participants higher in trait self-control, whereas those lower in trait self
      control exhibited a non-significant trend in the opposite direction. Thus,
      participants higher in trait self-control showed a positivity bias after
      contemplating death, which may help explain why they tend to enjoy more positive
      outcomes in life. 

PMID- 24083596
TI  - MicroRNA-302b suppresses cell proliferation by targeting EGFR in human
      hepatocellular carcinoma SMMC-7721 cells.
AB  - BACKGROUND: MicroRNAs are regulators that can play an essential role in
      tumorigenesis. Although miR-302 families have been suggested to be tumor
      repressors in human cancer, the mechanism by which they suppress tumor
      development remains to be defined. In this study, we discover that miR302b
      suppresses tumor proliferation may due to directly targeting EGFR in human
      hepatocellular carcinoma (HCC). METHODS: QRT-PCR was used to assess miR-302b and
      EGFR expression in 27 pairs of clinical hepatocellular carcinoma tissues and
      their corresponding adjacent nontumorous liver tissues. MTT, colony formation,
      immunofluorescence staining, and cell cycle assays were used to examine the tumor
      suppressor role of miR302b in cell proliferation. Luciferase assays were
      performed to assess the EGFR was a novel target of miR-302b. Western blot assay
      was used to validate the protein expression level. RESULTS: We demonstrated that
      miR-302b was frequently down-regulated, whereas EGFR was up-regulated in 27 pairs
      of clinical HCC and non-tumorous counterparts. The dual-luciferase reporter
      assays revealed that EGFR was a novel target of miR-302b. Re-expression of miR
      302b resulted in the inhibition of proliferation in hepatocellular carcinoma SMMC
      7721 cells. The silencing of EGFR by miR-302b or siEGFR led to down-regulation of
      proliferation-related proteins, such as AKT2, CCND1, and CDK2. CONCLUSION: miR
      302b suppresses HCC growth may due to targeting the EGFR/AKT2/CCND1 pathway.

PMID- 24083598
TI  - Circadian transcriptome analysis in human fibroblasts from Hunter syndrome and
      impact of iduronate-2-sulfatase treatment.
AB  - BACKGROUND: Hunter syndrome (HS) is a lysosomal storage disease caused by
      iduronate-2-sulfatase (IDS) deficiency and loss of ability to break down and
      recycle the glycosaminoglycans, heparan and dermatan sulfate, leading to
      impairment of cellular processes and cell death. Cell activities and functioning
      of intracellular organelles are controlled by the clock genes (CGs), driving the
      rhythmic expression of clock controlled genes (CCGs). We aimed to evaluate the
      expression of CGs and downstream CCGs in HS, before and after enzyme replacement
      treatment with IDS. METHODS: The expression levels of CGs and CCGs were evaluated
      by a whole transcriptome analysis through Next Generation Sequencing in normal
      primary human fibroblasts and fibroblasts of patients affected by HS before and
      24 h/144 h after IDS treatment. The time related expression of CGs after
      synchronization by serum shock was also evaluated by qRT-PCR before and after 24
      hours of IDS treatment. RESULTS: In HS fibroblasts we found altered expression of
      several CGs and CCGs, with dynamic changes 24 h and 144 h after IDS treatment. A
      semantic hypergraph-based analysis highlighted five gene clusters significantly
      associated to important biological processes or pathways, and five genes, AHR,
      HIF1A, CRY1, ITGA5 and EIF2B3, proven to be central players in these pathways.
      After synchronization by serum shock and 24 h treatment with IDS the expression
      of ARNTL2 at 10 h (p = 0.036), PER1 at 4 h (p = 0.019), PER2 at 10 h (p = 0.041)
      and 16 h (p = 0.043) changed in HS fibroblasts. CONCLUSION: CG and CCG expression
      is altered in HS fibroblasts and IDS treatment determines dynamic modifications,
      suggesting a direct involvement of the CG machinery in the physiopathology of
      cellular derangements that characterize HS.

PMID- 24083599
TI  - Effectivity of long antigen exposition dendritic cell therapy (LANEXDC(r)) in the
      palliative treatment of pancreatic cancer.
AB  - PURPOSE: In pancreatic cancer median survival times range around 6, 6 to 6,9
      months. Here we retrospectively analyzed the outcome of immunotherapy in the
      additional palliative treatment of pancreatic cancer with long antigen exposition
      dendritic cell therapy (LANEX-DC((r))) in 138 patients who were treated at our
      institution. PATIENTS: Data were available of 134 patients (97.1%). The median
      interval between first diagnosis and start of treatment was 1.4 months. RESULTS:
      Therapy was well tolerated and no serious side effects were observed. The
      survival rate after 6 months was 72.2 % and afters 9 month 50.4%. The median
      survival time according to Kaplan- Meier regression analysis was 8.9 months.
      Median survival was significantly higher in the group of patients who started
      immunotherapy within 2 months following diagnosis (p=0.029) or repeated
      immunotherapy (p=0.027). Interestingly, younger patients <= 60 years of age lived
      significantly longer as patients > 60 years of age (p = 0.022). CONCLUSION: We
      were able to demonstrate in a large retrospective analysis that additional
      treatment with dendritic cells (LANEX-DC((r))) is highly effective and extends
      the median survival times up to 8.9 months. Furthermore we were able to
      demonstrate that median survival can be increased by early beginning and
      repetition of LANEX-DC((r)) treatment.

PMID- 24083600
TI  - Sudden infant death following hexavalent vaccination: a neuropathologic study.
AB  - We examined a large number of sudden infant death syndrome victims in order to
      point out a possible causal relationship between a previous hexavalent
      vaccination and the sudden infant death. We selected 110 cases submitted to in
      depth histological examination of the autonomic nervous system and provided with
      detailed clinical and environmental information. In 13 cases (11.8%) the death
      occurred in temporal association with administration of the hexavalent vaccine
      (from 1 to 7 days). In none of these victims congenital developmental alterations
      of the main nervous structures regulating the vital functions were observed. Only
      the hypoplasia of the arcuate nucleus was present in 5 cases. In one case in
      particular an acquired hyperacute encephalitis of the tractus solitarii nucleus
      was diagnosed in the brainstem. This study does not prove a causal relationship
      between the hexavalent vaccination and SIDS. However, we hypothesize that vaccine
      components could have a direct role in sparking off a lethal outcome in
      vulnerable babies. In conclusion, we sustain the need that deaths occurring in a
      short space of time after hexavalent vaccination are appropriately investigated
      and submitted to a post-mortem examination particularly of the autonomic nervous
      system by an expert pathologist to objectively evaluate the possible causative
      role of the vaccine in SIDS. 

PMID- 24083601
TI  - Melting profiles may affect detection of residual HPV L1 gene DNA fragments in
      Gardasil(r).
AB  - Gardasil(r) is a quadrivalent human papillomavirus (HPV) protein-based vaccine
      containing genotype-specific L1 capsid proteins of HPV-16, HPV-18, HPV-6 and HPV
      11 in the form of virus-like-particles (VLPs) as the active ingredient. The VLPs
      are produced by a DNA recombinant technology. It is uncertain if the residual HPV
      L1 gene DNA fragments in the vaccine products are considered contaminants or
      excipients of the Gardasil(r) vaccine. Because naked viral DNA fragments, if
      present in the vaccine, may bind to the insoluble amorphous aluminum
      hydroxyphosphate sulfate (AAHS) adjuvant which may help deliver the foreign DNA
      into macrophages, causing unintended pathophysiologic effects, experiments were
      undertaken to develop tests for HPV L1 gene DNA fragments in the final products
      of Gardasil(r) by polymerase chain reaction (PCR) and direct DNA sequencing. The
      results showed that while the HPV-11 and HPV-18 L1 gene DNA fragments in
      Gardasil(r) were readily amplified by the common GP6/MY11 degenerate consensus
      primers, the HPV-16 L1 gene DNA may need specially designed non-degenerate PCR
      primers for amplification at different regions of the L1 gene and different
      stringency conditions for detection. These variable melting profiles of HPV DNA
      in the insoluble fraction of the Gardasil(r) vaccine suggest that the HPV DNA
      fragments are firmly bound to the aluminum AAHS adjuvant. All methods developed
      for detecting residual HPV DNA in the vaccine Gardasil(r) for quality assurance
      must take into consideration the variable melting profiles of the DNA to avoid
      false negative results.

PMID- 24083602
TI  - Selective elevation of circulating CCL2/MCP1 levels in patients with longstanding
      post-vaccinal macrophagic myofasciitis and ASIA.
AB  - Several medical conditions sharing similar signs and symptoms may be related to
      immune adjuvants. These conditions described as ASIA (Autoimmune/inflammatory
      Syndrome Induced by Adjuvants), include a condition characterized by macrophagic
      myofasciitis (MMF) assessing long-term persistence of vaccine derived-alum
      adjuvants into macrophages at sites of previous immunization. Despite increasing
      data describing clinical manifestations of ASIA have been reported, biological
      markers are particularly lacking for their characterization and follow up. We
      report an extensive cytokine screening performed in serum from 44 MMF patients
      compared both to sex and age matched healthy controls and to patients with
      various types of inflammatory neuromuscular diseases. Thirty cytokines were
      quantified using combination of Luminex(r) technology and ELISA. There was
      significant mean increase of serum levels of the monocytechemoattractant protein
      1 (CCL2/MCP-1) in MMF patients compared to healthy subjects. MMF patients showed
      no elevation of other cytokines. This contrasted with inflammatory patients in
      whom CCL2/MCP-1 serum levels were unchanged, whereas several other inflammatory
      cytokines were elevated (IL1beta, IL5 and CCL3/MIP1alpha). These results suggest
      that CCL2 may represent a biological marker relevant to the pathophysiology of
      MMF rather than a non specific inflammatory marker and that it should be checked
      in the other syndromes constitutive of ASIA. 

PMID- 24083604
TI  - Transition-state-guided drug design for treatment of parasitic neglected tropical
      diseases.
AB  - Many of the deadliest neglected tropical diseases are caused by protozoan and
      helminthic parasites. These organisms have evolved several enzymes to exploit
      their host's metabolic resources and evade immune responses. Because these
      essential proteins are absent in humans, they are targets for antiparasitic drug
      development. Despite decades of investigation, no therapy has been successful in
      the eradication of these diseases, so new approaches are desired. Chemically
      stable analogues of the transition states of enzymatic reactions are often potent
      inhibitors, and several examples of clinically effective compounds are known for
      other diseases. The design of transition-state analogues is aided by structural
      models of the transition state, which are obtained by complementing experimental
      measurement of kinetic isotope effects with theoretical calculations. Such
      transition-state-guided inhibitor design has been demonstrated for human, bovine,
      malarial, and trypanosomal enzymes of the purine salvage pathway, including
      purine nucleoside phosphorylase, nucleoside hydrolases, and adenosine deaminase.
      Cysteine proteases, trans-sialidase, 1-deoxy-d-xylulose-5-phosphate
      reductoisomerase, and trypanothione synthetase are presented as additional
      candidates for application of transition-state analysis with the goal of
      identifying new leads for the treatment of parasitic neglected tropical diseases.

PMID- 24083603
TI  - Targeting protozoan parasite metabolism: glycolytic enzymes in the therapeutic
      crosshairs.
AB  - Glycolysis is an important metabolic pathway for most organisms, including
      protozoan parasites. Many of these primitive eukaryotes have streamlined their
      metabolism, favoring glycolysis for generating ATP in the glucose-rich
      environments in which they reside. Therefore, the enzymes involved in hexose
      metabolism could prove to be attractive targets for therapeutic development. This
      hypothesis is supported by a number of chemical and genetic validation studies.
      Additionally, the peculiar biochemistry of many of the components, along with
      limited protein sequence identity emphasizes the likelihood of developing
      compounds that selectively inhibit the parasite enzymes. In this review, we
      examine the status of target validation at the genetic and/or chemical levels
      from the protozoan parasites. While the proteins from some species have been
      interrogated to the point that well-defined lead compounds have been identified
      with activities against both enzyme and parasite growth, progress in other
      systems has to date been limited. 

PMID- 24083605
TI  - Advantages and limitations of transgenic mice: the role of the Na+/Ca2+ exchanger
      in cardiac electrophysiology and arrhythmia.
AB  - In the search for novel antiarrhythmic strategies, the cardiac Na(+)/Ca(2+)
      exchanger (NCX) seems to be a promising target. Recent insights into the role of
      NCX in proarrhythmia stem from transgenic murine models with knockout or
      overexpression of NCX. There are significant differences regarding cellular
      electrophysiology, excitation-contraction coupling and Ca(2+) handling when
      comparing mice to higher mammal and most importantly human physiology. We here
      review findings derived from transgenic mouse models regarding the role of NCX in
      the generation of arrhythmia and discuss principle aspects to consider when
      translating physiological and pathophysiological mechanisms from mouse models
      into human physiology and the clinical context. 

PMID- 24083606
TI  - Module-activity relationship of G-quadruplex based DNA aptamers for human
      thrombin.
AB  - G-quadruplex based DNA aptamers for human thrombin are promising pharmaceuticals
      as anticoagulants. Initially discovered 15-mer DNA aptamer (15-TBA) has a minimal
      G-quadruplex structure which is able to inhibit thrombin. 15-TBA was modified and
      extended to improve aptamer activity and in vivo stability providing 31-TBA,
      NU172, RA-36, and some others as successful examples. In this paper an interplay
      between G-quadruplex (pharmacophore module) and additional modules has been
      studied. An original turbidimetric assay and conventional coagulation tests were
      applied to evaluate both inhibitory activity and type of inhibiting for aptamers
      constructed by exchanging the modules between 31- TBA and NU172. Additional
      modules strongly affect pharmacophore module inhibitory activity either enhancing
      or reducing it. RA-36 aptamer has two putative pharmacophore entities which also
      interplay being functionally non-equal. 5'- truncated RA-36 has half of the
      activity of RA-36, and the same as for 15-TBA. On the contrary 3'-truncated RA-36
      has intermediate activity in between 15-TBA and RA-36. These results indicate
      fine regulation of G-quadruplex inhibitory activity by additional modules, as
      well as non-trivial behavior of joined pharmacophore modules. 

PMID- 24083607
TI  - High-resolution bone imaging for osteoporosis diagnostics and therapy monitoring
      using clinical MDCT and MRI.
AB  - Osteoporosis is classified as a public health problem due to its increased risk
      for fragility fractures. Osteoporotic fractures, in particular spine and hip
      fractures, are associated with a high morbidity and mortality, and generate
      immense financial cost. The World Health Organisation (WHO) based the diagnosis
      of osteoporosis on the measurement of bone mineral density (BMD) using dual
      energy X-ray absorptiometry (DXA). However, BMD values of subjects with versus
      without osteoporotic fractures overlap. Furthermore, it was reported that the
      anti-fracture effects of drugs could be only partially explained by their effects
      on BMD. Bone strength reflects the integration of BMD and bone quality. The later
      can be partly determined by measurements of bone microstructure. Therefore,
      substantial research efforts have been undertaken to assess bone microstructure
      by using high-resolution imaging techniques, including high-resolution peripheral
      quantitative computed tomography (hr-pQCT), high-resolution multi-detector
      computed tomography (MDCT), and high-resolution magnetic resonance imaging (MRI).
      Clinical MDCT and MRI systems are broadly available and allow an adequate
      depiction of the bone microstructure at the clinically most important fracture
      sites, i.e. radius, spine and hip. Bone microstructure parameters and finite
      element models can be computed in high-resolution MDCT and MR images. These
      measurements improved the prediction of bone strength beyond the DXA-derived BMD
      and revealed pharmacotherapy effects, which are partly not captured by BMD.
      Therefore, high-resolution bone imaging using clinical MDCT and MRI may be
      beneficial for osteoporosis diagnostics and allow a highly sensitive monitoring
      of drug treatment, which plays an important role in the prevention of fragility
      fractures. 

PMID- 24083608
TI  - Classical neurotransmitters and neuropeptides involved in major depression in a
      multi-neurotransmitter system: a focus on antidepressant drugs.
AB  - We summarize the alterations of classical neurotransmitters and neuropeptides and
      the corresponding subreceptors involved in major depression. Neuronal circuits in
      the brainstem, hippocampus and hypothalamus are developed, since they can be used
      to derive a multimodal pharmacotherapy. In this sense, serotonin hypoactivity
      could occur through a strong presynaptic inhibition of glutaminergic neurons via
      the subtype 5 of metabotropic glutaminergic receptors, and noradrenaline
      hypoactivity could be due to an enhanced presynaptic inhibition of GABAergic
      neurons via GABAB receptors. In the hippocampus, dopamine hypoactivity leads to a
      decreased positive effect. In clinical trials, the antidepressant effect of drugs
      interfering with the mentioned subreceptors, for example the triple reuptake
      inhibitor amitifadine, is being investigated. Moreover, the alterations of
      neuropeptides, such as corticotropin-releasing hormone, neuropeptide Y and
      galanin are pointed out. The additional antidepressant effect of analogs,
      agonists and antagonists of the mentioned neuropeptides should be examined. 

PMID- 24083609
TI  - HPMA copolymer-bound doxorubicin induces immunogenic tumor cell death.
AB  - Treatment of murine EL4 T cell lymphoma with N-(2-hydroxypropyl)methacrylamide
      (HPMA) copolymer conjugates of doxorubicin (Dox) leads to complete tumor
      regression and to the development of therapy-dependent longlasting cancer
      resistance. This phenomenon occurs with two types of Dox conjugates tested,
      despite differences in the covalent linkage of Dox to the polymer carrier. Such a
      cancer resistance cannot fully express in conventional treatment with free Dox,
      due to substantial immunotoxicity of the treatment, which was not observed in the
      polymer conjugates. In this study, calreticulin (CRT) translocation and high
      mobility group box-1 protein (HMGB1) release was observed in EL4 cells treated
      with a conjugate releasing Dox by a pH-dependent manner. As a result, the treated
      tumor cells were engulfed by dendritic cells (DC) in vitro, and induced their
      expression of CD80, CD86, and MHC II maturation markers. Conjugates with Dox
      bound via an amide bond only increased translocation of HSPs to the membrane,
      which led to an elevated phagocytosis but was not sufficient to induce increase
      of the maturation markers on DCs in vitro. Both types of conjugates induced
      engulfment of the target tumor cells in vivo, that was more intense than that
      seen with free Dox. It means that the induction of anti-tumor immunity documented
      upon treatment of EL4 lymphoma with HPMA-bound Dox conjugates does not rely
      solely on CRT-mediated cell death, but involves multiple mechanisms. 

PMID- 24083610
TI  - Developmental regulated expression of anti- and pro-apoptotic BCL-2 family genes
      during human early embryonic development.
AB  - Apoptotic cell death has been reported in human oocytes and preimplantation
      embryos under in vivo and in vitro conditions. BCL-2 family proteins comprise
      both anti- and pro-apoptotic members, which are likely to play a key role in
      controlling oocyte and early embryo survival. However, very limited data are
      available on their expression kinetics during human early embryonic development.
      Using our DNA microarray data, we analyzed the expression pattern of 21 BCL-2
      family genes in human mature MII oocytes, day 3 embryos and day 5/6 blastocysts
      from patients who underwent in vitro fertilization (IVF). Selected genes were
      further validated by qRT-PCR and their subcellular localization analyzed by
      immunofluorescence confocal microscopy. Our results suggest a switch from oocyte
      inherited BCL-2 family transcripts, such as BCL2L10, to embryo-produced
      transcripts after embryonic genome activation, including BIK, BCL2L11 and NOXA.
      Moreover, the pro-apoptotic gene BCL2L13 was constitutively expressed throughout
      human early embryonic development. Remarkably, day 3 embryos expressed more BCL-2
      pro-apoptotic genes than mature MII oocytes and day 5/6 blastocysts, suggesting
      that embryos at this stage are more prone to apoptosis. This is further supported
      by an absence of cleaved Caspase-3 in the oocyte and its presence in the embryo.
      Using a drug that induces apoptosis (gambogic acid), we were able to show
      activated Caspase-3 in the oocyte in addition to an alteration of BCL2L13 protein
      localization. Similarly BCL2L13 localization was altered in degenerated oocytes.
      This study opens new perspectives for understanding the molecular regulation of
      human oocyte and pre-implantation embryo survival and death. 

PMID- 24083611
TI  - Inhibitors and prodrugs targeting CYP1: a novel approach in cancer prevention and
      therapy.
AB  - Since Human CYP1 enzymes catalyze the metabolic activation of procarcinogens and
      deactivation of certain anticancer drugs, the inhibition of these enzymes has
      been considered as an effective approach for chemoprevention and treatment of
      CYP1-mediated drug resistance. Recent knowledge relating to the enhanced
      expression of CYP1B1 in tumors also provided certain advantages in cancer therapy
      by the activation of prodrugs only in tumor cells. This review concentrates on
      the characterized CYP1 inhibitors and CYP1-activatied anticancer prodrugs. The
      mechanism for enzyme inhibition and activation of prodrugs, the cancer
      preventive/therapeutic potential of these chemicals and their related SARs are
      highlighted. According to their structural features, CYP1 inhibitors are divided
      into the following categories: flavonoids, trans-stilbenes, coumarins,
      terpenoids, alkaloids, quinones, isothiocyanates and synthetic aromatics. In the
      same way, CYP1-activatied prodrugs are categorized into four groups:
      benzothiazoles, flavonoids, stilbenes and alkylating agents. Almost all of these
      inhibitors and prodrugs are planar molecules with one aromatic ring and some have
      similarity with identified CYP1 substrates. CYP1 inhibitors could effectively
      block the procarcinogen-induced tumor initiation in animal models and benefit us
      with chemoprevention. The advent of Phortress and aminoflavone as clinical
      candidates shows promising perspectives in developing CYP1-mediated prodrugs as
      chemotherapeutic drugs that are specifically activated in tumors. All of these
      preclinical and clinical studies indicate that inhibitors and prodrugs target
      CYP1 are promising anticancer strategies. 

PMID- 24083612
TI  - HIV-1 inhibiting capacity of novel forms of presentation of GB virus C peptide
      domains is enhanced by coordination to gold compounds.
AB  - Following the report of beneficial effects of co-infection by GB virus C (GBV-C)
      for HIV-infected patients, we have studied synthetic GBV-C peptides and their
      relationship with HIV type-1. This paper reports the design and synthesis of new
      forms of presentation of two peptide inhibitors corresponding to the envelope
      proteins E1 and E2 of GBV-C, together with a study of their anti-HIV-1 activity.
      Homogeneous and heterogeneous multiple antigenic peptides (MAPs), lipophilic
      derivatizations, cyclization and peptide-gold conjugations are the chemical
      design strategies adopted. Our aim is to enhance the anti-viral potency of the
      GBV-C peptide domains. Of all the GBV-C peptide derivatives studied, peptide-gold
      complexes derived from the (22-39) sequence of the GBV-C E1 protein were the most
      active entry inhibitors. These results support the putative modulation of HIV-1
      infection by the GBV-C E1 protein and open new perspectives for the development
      of novel peptide-derived HIV-1 entry inhibitors. 

PMID- 24083613
TI  - Co-control of local air pollutants and CO2 in the Chinese iron and steel
      industry.
AB  - The present study proposes an integrated multipollutant cocontrol strategy
      framework in the context of the Chinese iron and steel industry. The unit cost of
      pollutant reduction (UCPR) was used to examine the cost-effectiveness of each
      emission reduction measure. The marginal abatement cost (MAC) curves for SO2,
      NOx, PM2.5, and CO2 were drawn based on the UCPR and the abatement potential. Air
      pollutant equivalence (APeq) captures the nature of the damage value-weights of
      various air pollutants and acts as uniformization multiple air pollutants index.
      Single pollutant abatement routes designed in accordance with the corresponding
      reduction targets revealed that the cocontrol strategy has promising potential.
      Moreover, with the same reduction cost limitations as the single pollutant
      abatement routes, the multipollutant cocontrol routes are able to obtain more
      desirable pollution reduction and health benefits. Co-control strategy generally
      shows cost-effective advantage over single-pollutant abatement strategy. The
      results are robust to changing parameters according to sensitivity analysis. Co
      control strategy would be an important step to achieve energy/carbon intensity
      targets and pollution control targets in China. Though cocontrol strategy has got
      some traction in policy debates, there are barriers to integrate it into policy
      making in the near future in China. 

PMID- 24083614
TI  - Strategies to reduce oxygen inhibition in photoinduced polymerization.

PMID- 24083615
TI  - Field evaluation in Chad of community usage of CD4 T lymphocyte counting by
      alternative single-platform flow cytometry.
AB  - BACKGROUND: Field and community evaluation of the routine usage of CD4 T counting
      platforms is essential in resource-poor countries for efficient and cost
      effective monitoring of HIV-infected adults and children attending health care
      centers. METHODS: We herein addressed the principal issues raised by the
      implementation of the single-platform, volumetric Auto40 flow cytometer (Apogee
      Flow Systems Ltd, Hemel Hempstead, UK) in 8 community HIV monitoring laboratories
      of different levels throughout Chad. This is a country with particularly
      difficult conditions, both in terms of climate and vast geographical territory,
      making the decentralization of the therapeutic management of HIV-infected
      patients challenging. RESULTS: The routine usage of the Auto40 flow cytometers
      for a period of 5 years (2008-2013) confirms the reliability and robustness of
      the analyzer for community-based CD4 T cell enumeration in terms of both absolute
      numbers and percentages to enable accurate monitoring of HIV-infected adults and
      children. However, our observations suggest that the Auto40 mini flow cytometer
      is not suitable for all laboratories as it is oversized and ultimately very
      expensive. CONCLUSION: The Chad experience with the Auto40 flow cytometer
      suggests that its usage in resource-limited settings should be mainly reserved to
      reference (level 1) or district (level 2) laboratories, rather than to
      laboratories of health care centres (level 3).

PMID- 24083616
TI  - Development of dual-function ELISA for effective antigen and antibody detection
      against H7 avian influenza virus.
AB  - BACKGROUND: Outbreaks in poultry involving influenza virus from H7 subtype have
      resulted in human infections, thus causing a major concern for public health, as
      well as for the poultry industry. Currently, no efficient rapid test is available
      for large-scale detection of either antigen or antibody of H7 avian influenza
      viruses. RESULTS: In the present study, a dual function ELISA was developed for
      the effective detection of antigen and antibody against H7 AIVs. The test was
      established based on antigen-capture-ELISA and epitope blocking ELISA. The two
      Mabs 62 and 98 which were exploited in the assay were identified to recognize two
      conformational neutralizing epitopes on H7 HA1. Both of the epitopes exist in all
      of the human H7 strains, including the recent H7N9 strain from China and > 96.6%
      of avian H7 strains. The dual ELISA was able to detect all of the five H7
      antigens tested without any cross reaction to other influenza subtypes. The
      antigen detection limit was less than 1 HA unit of H7. For antibody detection,
      the sensitivity and specificity of the dual ELISA was evaluated and compared to
      HI and microneutralization using immunized animal sera to different H7 strains
      and different subtypes of AIVs. Results indicated that antibodies to H7 were
      readily detected in immunized animal sera by the dual ELISA whereas specimens
      with antibodies to other AIVs yielded negative results. CONCLUSIONS: This is the
      first dual-function ELISA reported for either antigen or antibody detection
      against H7 AIVs. The assay was highly sensitive and 100% specific in both
      functions rendering it effective for H7 diagnosis.

PMID- 24083619
TI  - Impact of cooking, proving, and baking on the (poly)phenol content of wild
      blueberry.
AB  - Accumulating evidence suggests that diets rich in (poly)phenols may have positive
      effects on human health. Currently there is limited information regarding the
      effects of processing on the (poly)phenolic content of berries, in particular in
      processes related to the baking industry. This study investigated the impact of
      cooking, proving, and baking on the anthocyanin, procyanidin, flavonol, and
      phenolic acid contents of wild blueberry using HPLC with UV and fluorescence
      detection. Anthocyanin levels decreased during cooking, proving, and baking,
      whereas no significant changes were observed for total procyanidins. However,
      lower molecular weight procyanidins increased and high molecular weight oligomers
      decreased during the process. Quercetin and ferulic and caffeic acid levels
      remained constant, whereas increases were found for chlorogenic acid. Due to
      their possible health benefits, a better understanding of the impact of
      processing is important to maximize the retention of these phytochemicals in
      berry-containing products. 

PMID- 24083617
TI  - Measures of health-related quality of life and socio-cultural aspects in young
      patients who after mandible primary reconstruction with free fibula flap.
AB  - BACKGROUND: The reconstruction of mandibular defects after trauma or tumor
      resection is one of the most challenging problems facing reconstructive surgeons.
      Although the primary intended outcome of surgery to treat head-and-neck
      malignancies is still the disease-free survival of the patient, health-related
      quality of life (HRQOL) is now seen as an essential secondary outcome. This study
      aims to evaluate HRQOL outcomes in young patients undergoing primary mandible
      reconstruction with free fibula flap and to collect information about their socio
      cultural situation. METHODS: The HRQOL outcomes of 25 young patients after
      primary mandible reconstruction with free fibula flap for mandible malignancies
      were assessed using the Medical Outcomes Study-Short Form-36 (MOS SF-36) and
      University of Washington Quality of Life (UW-QOL) questionnaires 12 months
      postoperatively. RESULTS: Using the UW-QOL questionnaire, the best-scoring domain
      was 'pain', whereas 'chewing' and 'anxiety' were given the lowest scores. Using
      the MOS SF-36 questionnaire, the best-scoring domain was 'physical functioning',
      while 'bodily pain' and 'general health' also scored well. CONCLUSIONS: Mandible
      reconstruction with fibula flap will significantly influence a young patient's
      HRQOL. Young patients pay more attention to postoperative facial appearance; this
      should be considered in surgical planning. The socio-cultural data show a fairly
      low level of education for the majority of patients.

PMID- 24083620
TI  - A double diastereoselective Michael-type addition as an entry to conformationally
      restricted tn antigen mimics.
AB  - A totally stereocontrolled C-Michael addition of serine-equivalent C-nucleophiles
      to tri-O-benzyl-2-nitro-d-galactal was used as the key step to synthesize several
      pyrano[3,2-b]pyrrole structures. These scaffolds could be regarded as
      conformationally restricted Tn antigen mimics, as we have demonstrated by
      biological assays. The pyranose rings retain their (4)C1 chair conformation, as
      shown by molecular modeling and NMR spectroscopy. The expected bioactivity was
      established by a competition-tailored enzyme-linked lectin assay using both
      soybean and Vicia villosa agglutinins as model lectins. The facile described
      synthetic route and the strategic combination of computational and experimental
      techniques to reveal conformational features and bioactivity demonstrate the
      prepared glycomimics to be promising candidates for further exploitation of this
      scaffold to give glycans for lectin blocking and vaccination. 

PMID- 24083621
TI  - Aspects of reliability and validity of the Swedish version of the Self-Efficacy
      for Exercise Scale for older people.
AB  - The aim was to test aspects of reliability and validity of a Swedish version of
      the Self-Efficacy for Exercise Scale (SEE-SV) for older people. Floor and ceiling
      effects, item-total correlation, internal consistency, test--retest reliability,
      content and construct validity were tested on 39 older people, mean age 72 years
      (SD 3.3). Content validity was also tested on five physical therapists. The
      results showed no floor and ceiling effects. The ICC for the total score was 0.79
      (95% CI 0.61-0.89). The median weighted kappa coefficients square for the
      individual items was 0.63. Item-to-total correlation varied between 0.64 and 0.86
      and Cronbach's Alpha for all items was >0.92. The correlations between SEE-SV and
      the SF-36 Mental Health and Bodily Pain subscales were r(s) = 0.50 and r(s) =
      0.30 (ns), respectively. The correlation between SEE-SV and self-assessed
      physical activity was r(s) = 0.13 (ns). Eighty-nine percent responded that the
      items were relevant and 92% that no item should be excluded. All physical
      therapists considered the items relevant, but the written instructions could be
      improved. In conclusion, SEE-SV has good item-to-total correlation, satisfactory
      internal consistence and substantial test--retest reliability. Our results show
      satisfactory content validity; however, studies are needed to further evaluate
      construct validity and to evaluate other aspects such as predicitve validity and
      responsiveness.

PMID- 24083622
TI  - Progress in novel cognitive enhancers for cognitive aging and Alzheimer's
      disease.
AB  - Increased knowledge of the biology of synaptic function has led to the
      development of novel cognitive-enhancing therapeutic strategies with the
      potential for increased efficacy and safety. This editorial highlights a diverse
      array of approaches currently being explored to target cognitive dysfunction due
      to aging and/or Alzheimer's disease. 

PMID- 24083623
TI  - In vivo tumor targeting and image-guided drug delivery with antibody-conjugated,
      radiolabeled mesoporous silica nanoparticles.
AB  - Since the first use of biocompatible mesoporous silica (mSiO2) nanoparticles as
      drug delivery vehicles, in vivo tumor targeted imaging and enhanced anticancer
      drug delivery has remained a major challenge. In this work, we describe the
      development of functionalized mSiO2 nanoparticles for actively targeted positron
      emission tomography (PET) imaging and drug delivery in 4T1 murine breast tumor
      bearing mice. Our structural design involves the synthesis, surface
      functionalization with thiol groups, PEGylation, TRC105 antibody (specific for
      CD105/endoglin) conjugation, and (64)Cu-labeling of uniform 80 nm sized mSiO2
      nanoparticles. Systematic in vivo tumor targeting studies clearly demonstrated
      that (64)Cu-NOTA-mSiO2-PEG-TRC105 could accumulate prominently at the 4T1 tumor
      site via both the enhanced permeability and retention effect and TRC105-mediated
      binding to tumor vasculature CD105. As a proof-of-concept, we also demonstrated
      successful enhanced tumor targeted delivery of doxorubicin (DOX) in 4T1 tumor
      bearing mice after intravenous injection of DOX-loaded NOTA-mSiO2-PEG-TRC105,
      which holds great potential for future image-guided drug delivery and targeted
      cancer therapy. 

PMID- 24083626
TI  - Long-term clinical efficacy and safety of adding cilostazol to dual antiplatelet
      therapy for patients undergoing PCI: a meta-analysis of randomized trials with
      adjusted indirect comparisons.
AB  - OBJECTIVE: To assess the long-term clinical efficacy and safety of adding
      cilostazol to aspirin plus clopidogrel (triple antiplatelet therapy, TAT) in
      patients undergoing percutaneous coronary intervention (PCI) and explore its role
      in the era of new generation adenosine diphosphate (ADP)-receptor antagonists.
      METHODS: PUBMED, EMBASE, and the Cochrane Central Register of Controlled Trials
      were searched for randomized controlled trials (RCTs) comparing TAT versus dual
      antiplatelet therapy (DAT), followed by a manual search. Then, a meta-analysis of
      RCTs comparing TAT versus standard DAT in patients undergoing PCI was performed.
      Furthermore, indirect comparisons of TAT versus new generation ADP-receptor
      antagonist based DAT (prasugrel or ticagrelor based DAT) were undertaken, with
      standard DAT as a common comparator. The included end-points were major adverse
      cardiovascular event (MACE), target lesion revascularization (TLR), target vessel
      revascularization (TVR), death, myocardial infarction (MI), stent thrombosis,
      bleeding and other drug adverse events. RESULTS: Twelve RCTs with a total of
      31,789 patients were included. Compared with standard DAT (n = 2551), TAT (n =
      2545) significantly reduced the incidence of MACE (OR: 0.56, 95% CI: 0.47-0.68, P
      < 0.00001), TLR (OR: 0.51, 95% CI: 0.34-0.75, P = 0.0006) and TVR (OR: 0.59, 95%
      CI: 0.46-0.75, P < 0.0001), and did not change significantly in death (OR: 0.68,
      95% CI: 0.44-1.05, P = 0.08), MI (OR: 0.80, 95% CI: 0.45-1.44, P = 0.46), stent
      thrombosis (OR: 0.61, 95% CI: 0.27-1.36, P = 0.23), major bleeding (OR: 1.42, 95%
      CI: 0.52-3.85, P = 0.49) and overall bleeding (OR: 1.16, 95% CI: 0.79-1.69, P =
      0.45). Compared with prasugrel (n = 6813) or ticagrelor based DAT (n = 6732), TAT
      (n = 2545) further reduced the incidence of MACE (OR: 0.80, 95% CI: 0.72-0.90, P
      = 0.0012; OR: 0.83, 95% CI: 0.75-0.92, P = 0.0003, respectively). CONCLUSIONS:
      Compared with standard DAT, the long-term use of TAT in patients with PCI gives
      more benefits in reducing the incidence of MACE, TLR and TVR without increasing
      bleeding. Furthermore, it might be superior to prasugrel or ticagrelor based DAT
      in term of MACE, which needs to be confirmed by future studies with direct
      comparisons.

PMID- 24083625
TI  - Activating group recycling in action: a rhodium-catalyzed carbothiolation route
      to substituted isoquinolines.
AB  - A new rhodium(I) catalyst allows practical and efficient alkyne carbothiolation
      reactions to be achieved on synthetically useful ketone-bearing aryl methyl
      sulfides. The carbothiolation adducts, featuring a 'recycled methyl sulfide'
      activating group, are convenient precursors to highly substituted isoquinolines. 

PMID- 24083627
TI  - Quantitative analysis of scanning tunneling microscopy images of mixed-ligand
      functionalized nanoparticles.
AB  - Ligand-protected gold nanoparticles exhibit large local curvatures, features
      rapidly varying over small scales, and chemical heterogeneity. Their imaging by
      scanning tunneling microscopy (STM) can, in principle, provide direct information
      on the architecture of their ligand shell, yet STM images require laborious
      analysis and are challenging to interpret. Here, we report a straightforward,
      robust, and rigorous method for the quantitative analysis of the multiscale
      features contained in STM images of samples consisting of functionalized Au
      nanoparticles deposited onto Au/mica. The method relies on the analysis of the
      topographical power spectral density (PSD) and allows us to extract the
      characteristic length scales of the features exhibited by nanoparticles in STM
      images. For the mixed-ligand-protected Au nanoparticles analyzed here, the
      characteristic length scale is 1.2 +/- 0.1 nm, whereas for the homoligand Au NPs
      this scale is 0.75 +/- 0.05 nm. These length scales represent spatial
      correlations independent of scanning parameters, and hence the features in the
      PSD can be ascribed to a fingerprint of the STM contrast of ligand-protected
      nanoparticles. PSD spectra from images recorded at different laboratories using
      different microscopes and operators can be overlapped across most of the
      frequency range, proving that the features in the STM images of nanoparticles can
      be compared and reproduced. 

PMID- 24083624
TI  - Disparities in race/ethnicity and socioeconomic status: risk of mortality of
      breast cancer patients in the California Cancer Registry, 2000-2010.
AB  - BACKGROUND: Racial disparities in breast cancer survival have been well
      documented. This study examines the association of race/ethnicity and
      socioeconomic status (SES) on breast cancer-specific mortality in a large
      population of women with invasive breast cancer. METHODS: We identified 179,143
      cases of stages 1-3 first primary female invasive breast cancer from the
      California Cancer Registry from January, 2000 through December, 2010. Cox
      regression, adjusted for age, year of diagnosis, grade, and ER/PR/HER2 subtype,
      was used to assess the association of race/ethnicity on breast cancer-specific
      mortality within strata of stage and SES. Hazard ratios (HR) and 95% confidence
      intervals were reported. RESULTS: Stage 1: There was no increased risk of
      mortality for any race/ethnicity when compared with whites within all SES strata.
      Stage 2: Hispanics (HR = 0.85; 0.75, 0.97) in the lowest SES category had a
      reduced risk of mortality.. Blacks had the same risk of mortality as whites in
      the lowest SES category but an increased risk of mortality in the intermediate
      (HR = 1.66; 1.34, 2.06) and highest (HR = 1.41; 1.15, 1.73) SES categories. Stage
      3: Hispanics (HR = 0.74; 0.64, 0.85) and APIs (HR = 0.64; 0.50, 0.82) in the
      lowest SES category had a reduced risk while blacks had similar mortality as
      whites. Blacks had an increased risk of mortality in the intermediate (HR = 1.52;
      1.20, 1.92) and highest (HR = 1.53; 1.22, 1.92) SES categories. CONCLUSIONS: When
      analysis of breast cancer-specific mortality is adjusted for age and year of
      diagnosis, ER/PR/HER2 subtype, and tumor grade and cases compared within stage
      and SES strata, much of the black/white disparity disappears. SES plays a
      prominent role in breast cancer-specific mortality but it does not fully explain
      the racial/ethnic disparities and continued research in genetic, societal, and
      lifestyle factors is warranted.

PMID- 24083629
TI  - Use of ultrasound attenuation spectroscopy to determine the size distribution of
      clay tactoids in aqueous suspensions.
AB  - The dispersion processes of aqueous samples of clay are studied using ultrasound
      attenuation spectroscopy. The attenuation spectra that are acquired in the
      frequency range 10-100 MHz are used to determine the particle size distributions
      (PSDs) for different concentrations and ages of the clay suspensions. Our
      analysis, using equivalent spherical diameter (ESD) for circular discs under
      Stokes drag in samples of concentrations greater than 1.5% w/v, shows that a
      substantial fraction of the aggregates in suspension are actually tactoids that
      are composed of more than one platelet. This is in contrast to the general belief
      that clay disperses into individual platelets in the concentration range where
      their suspensions exhibit glassy behavior. We conclude that the incomplete
      fragmentation of the clay tactoids arises from the rapid enhancement of the
      intertactoid Coulombic repulsion. 

PMID- 24083630
TI  - Conversion of biomass into chemicals over metal catalysts.

PMID- 24083628
TI  - Effect of mandibular mobilization on electromyographic signals in muscles of
      mastication and static balance in individuals with temporomandibular disorder:
      study protocol for a randomized controlled trial.
AB  - BACKGROUND: The stomatognathic system and dysfunction in this system may be
      related to postural control. The proposal of the present study is to assess the
      effect of mandibular mobilization in individuals with temporomandibular disorder
      using surface electromyography of the muscles of mastication and stabilometric
      variables. METHODS/DESIGN: A randomized, controlled, blind, clinical trial will
      be carried out, with the participants divided into three groups: 1) facial
      massage therapy (control group), 2) nonspecific mandibular mobilization and 3)
      specific mandibular mobilization. All groups will be assessed before and after
      treatment using the Research Diagnostic Criteria for Temporomandibular Disorders,
      surface electromyography of the masseter and temporal muscles and stabilometry.
      This study is registered with the Brazilian Registry of Clinical Trials
      (RBR9x8ssz). DISCUSSION: A large number of studies have employed surface
      electromyography to investigate the function/dysfunction of the muscles of
      mastication and associations with signs and symptoms of temporomandibular
      disorders. However, it has not yet been determined whether stabilometric
      variables offer adequate reliability in patients with this disorder. The results
      of the proposed study will help determine whether specific and/or nonspecific
      mandibular mobilization exerts an effect on the muscles of mastication and
      postural control. Moreover, if an effect is detected, the methodology defined in
      the proposed study will allow identifying whether the effect is local (found only
      in the muscles of mastication), global (found only in postural control) or
      generalized.

PMID- 24083631
TI  - Impact of comorbidities on the treatment of chronic myeloid leukemia with
      tyrosine-kinase inhibitors.
AB  - The median age at diagnosis of chronic myeloid leukemia (CML) is between 60 and
      65 years in most epidemiologic registries. Rather than age per se, a
      comprehensive evaluation of comorbidities may describe more properly the general
      clinical status of a patient. Tyrosine-kinase inhibitors (TKIs) have a different
      tolerability profile, and some adverse events (AEs) are peculiar of each drug, in
      particular, in presence of predisposing factors (comorbidities, concomitant
      medications). This article will review the impact of comorbidities in the safety
      and outcome of CML patients treated with TKIs. We will explore how the
      comorbidity status may be considered, together with CML-related factors, in the
      selection of the TKI in order to optimize treatment. 

PMID- 24083632
TI  - Development and psychometric properties of a scale for measuring internal
      participation from a patient and health care professional perspective.
AB  - BACKGROUND: Effective patient-centred health care requires internal
      participation, which is defined as interprofessional patient-centred teamwork.
      Many scales are designed for measuring teamwork from the perspective of one type
      of health care professional (e.g. physician or nurse), rather than for the use
      for all health care professionals as well as patients. Hence, this paper's
      purpose is to develop a scale for measuring internal participation from all
      relevant perspectives and to check its psychometric properties. METHODS: In a
      multicentre cross-sectional study, a 6-item Internal Participation Scale (IPS)
      was developed and administered to 661 health care professionals (staff) and 1419
      patients in 15 rehabilitation clinics to test item characteristics, acceptance,
      reliability (internal consistency) and construct validity. Additionally, we
      performed an exploratory factor analysis (EFA) to determine the factorial
      structure and explained variance. Confirmatory factor analysis (CFA) was used to
      verify the theoretically assumed one-dimensional factorial structure. RESULTS: A
      total of 275 health care professionals and 662 patients participated, and the
      complete data sets of 272 staff members and 536 patients were included in the
      final analysis. The discrimination index was above .4 for all items in both
      samples. Internal consistency was very good, with Cronbach's alpha equalling .87
      for the staff and .88 for the patient sample. EFA supported a one-dimensional
      structure of the instrument (explained variance: 61.1% (staff) and 62.3%
      (patients)). CFA verified the factorial structure, with the factor loadings
      exceeding .4 for five of six items in both samples. Global goodness-of-fit
      indices indicated a good model fit, with a Tucker-Lewis index (TLI) of .974
      (staff) and .976 (patients) and a comparative fit index (CFI) of .988 (staff) and
      .989 (patients). The root mean square error of approximation (RMSEA) amounted to
      .068 for the patient sample and .069 for the staff sample. There is evidence of
      construct validity for both populations. CONCLUSIONS: The analysis of the scale's
      psychometric properties resulted in good values. The scale is a promising
      instrument to assess internal participation from the perspective of both patients
      and staff. Further research should investigate the scale's psychometric
      properties in other interprofessional health care settings to examine its
      generalizability as well as its sensitivity to change.

PMID- 24083634
TI  - Gestational diabetes and macrosomia by race/ethnicity in Hawaii.
AB  - BACKGROUND: Gestational diabetes (GDM) has been shown to have long-term sequelae
      for both the mother and infant. Women with GDM are at increased risk of
      macrosomia, which predisposes the infant to birth injuries. Previous studies
      noted increased rates of GDM in Asian and Pacific Islander (API) women; however,
      the rate of macrosomia in API women with GDM is unclear. The objective of this
      study was to examine the relationship between ethnicity, gestational diabetes
      (GDM), and macrosomia in Hawaii. METHODS: A retrospective cohort study was
      performed using Hawaii Pregnancy Risk Assessment Monitoring System (PRAMS) data.
      Data from 2009-2011, linked with selected items from birth certificates, were
      used to examine GDM and macrosomia by ethnicity. SAS-callable SUDAAN 10.0 was
      used to generate odds ratios, point estimates and standard errors. RESULTS: Data
      from 4735 respondents were weighted to represent all pregnancies resulting in
      live births in Hawaii from 2009-2011. The overall prevalence of GDM in Hawaii was
      10.9%. The highest prevalence of GDM was in Filipina (13.1%) and Hawaiian/Pacific
      Islander (12.1%) women. The lowest prevalence was in white women (7.4%).
      Hawaiian/Pacific Islander, Filipina, and other Asian women all had an increased
      risk of GDM compared to white women using bivariate analysis. Adjusting for
      obesity, age, maternal nativity, and smoking, Asian Pacific Islander (API) women,
      which includes Hawaiian/Pacific Islander, Filipina, and other Asian women, had a
      50% increased odds of having GDM compared to white women when compared using
      multivariate analysis. Among women with GDM, the highest prevalence of macrosomia
      was in white women (14.5%) while the lowest was in Filipina (5.3%) women.
      CONCLUSIONS: API women in Hawaii have increased rates of GDM compared to white
      women. Paradoxically, this elevated GDM risk in API women is not associated with
      an increased rate of macrosomia. This suggests the relationship between GDM and
      macrosomia is more complex in this population.

PMID- 24083635
TI  - A framework for outcome-level evaluation of in-service training of health care
      workers.
AB  - BACKGROUND: In-service training is a key strategic approach to addressing the
      severe shortage of health care workers in many countries. However, there is a
      lack of evidence linking these health care worker trainings to improved health
      outcomes. In response, the United States President's Emergency Plan for AIDS
      Relief's Human Resources for Health Technical Working Group initiated a project
      to develop an outcome-focused training evaluation framework. This paper presents
      the methods and results of that project. METHODS: A general inductive methodology
      was used for the conceptualization and development of the framework. Fifteen key
      informant interviews were conducted to explore contextual factors, perceived
      needs, barriers and facilitators affecting the evaluation of training outcomes.
      In addition, a thematic analysis of 70 published articles reporting health care
      worker training outcomes identified key themes and categories. These were
      integrated, synthesized and compared to several existing training evaluation
      models. This formed an overall typology which was used to draft a new framework.
      Finally, the framework was refined and validated through an iterative process of
      feedback, pilot testing and revision. RESULTS: The inductive process resulted in
      identification of themes and categories, as well as relationships among several
      levels and types of outcomes. The resulting framework includes nine distinct
      types of outcomes that can be evaluated, which are organized within three nested
      levels: individual, organizational and health system/population. The outcome
      types are: (1) individual knowledge, attitudes and skills; (2) individual
      performance; (3) individual patient health; (4) organizational systems; (5)
      organizational performance; (6) organizational-level patient health; (7) health
      systems; (8) population-level performance; and (9) population-level health. The
      framework also addresses contextual factors which may influence the outcomes of
      training, as well as the ability of evaluators to determine training outcomes. In
      addition, a group of user-friendly resources, the Training Evaluation Framework
      and Tools (TEFT) were created to help evaluators and stakeholders understand and
      apply the framework. CONCLUSIONS: Feedback from pilot users suggests that using
      the framework and accompanying tools may support outcome evaluation planning.
      Further assessment will assist in strengthening guidelines and tools for
      operationalization.

PMID- 24083636
TI  - Effects of testosterone treatment on body composition in males with testosterone
      deficiency syndrome.
AB  - OBJECTIVE: We evaluated the safety of testosterone treatment and its efficacy on
      body composition in males with testosterone deficiency syndrome (TDS) over 24
      months. METHODS: 50 males aged 50-65 years with TDS (Aging Males Symptoms Scale
      [AMS] > 26 and calculated free testosterone [cFT] 250 pmol/l) were administered
      50 mg testosterone gel daily for one year. During the second year, patients
      received 1000 mg of testosterone undecanoate every 2-3 months. Outcome measures
      were clinical chemistry values and total testosterone; sex hormone-binding
      globulin and cFT, changes in AMS and International Prostate Symptom Score; and
      changes in body composition measured by dual-energy-x-ray absorptiometry.
      RESULTS: There were no clinically significant changes in clinical chemistry
      safety parameters. There were significant improvements in both total and cFT and
      in AMS scores after three months (p < 0.001). Lean mass increased 2.35% at 12
      months and 4.5% at 24 months, but proportionally more muscle mass was gained in
      arms and legs than in the trunk. Fat mass decreased 4.2% at 12 months and 9.1% at
      24 months. CONCLUSIONS: Testosterone treatment in males with TDS leads to body
      changes affecting lean and fat mass with significant improvement in AMS scores,
      and has an excellent safety profile.

PMID- 24083637
TI  - Structure-activity relationships and identification of optmized CC-chemokine
      receptor CCR1, 5, and 8 metal-ion chelators.
AB  - Chemokine receptors are involved in trafficking of leukocytes and represent
      targets for autoimmune conditions, inflammatory diseases, viral infections, and
      cancer. We recently published CCR1, CCR8, and CCR5 agonists and positive
      modulators based on a three metal-ion chelator series: 2,2'-bipyridine, 1,10
      phenanthroline, and 2,2';6',2"-terpyridine. Here, we have performed an in-depth
      structure-activity relationship study and tested eight new optimized analogs.
      Using density functional theory calculations we demonstrate that the chelator
      zinc affinities depend on how electron-donating and -withdrawing substituents
      modulate the partial charges of chelating nitrogens. The zinc affinity was found
      to constitute the major factor for receptor potency, although the activity of
      some chelators deviate suggesting favorable or unfavorable interactions.
      Hydrophobic and halogen substituents are generally better accommodated in the
      receptors than polar groups. The new analog brominated terpyridine (29) resulted
      in the highest chelator potencies observed so far CCR1 (EC50: 0.49 MUM) and CCR8
      (EC50: 0.28 MUM). Furthermore, we identified the first selective CCR5 agonist
      chelator, meta dithiomethylated bipyridine (23). The structure-activity
      relationships contribute to small-molecule drug development, and the novel
      chelators constitute valuable tools for studies of structural mechanisms for
      chemokine receptor activation. 

PMID- 24083638
TI  - Glutaminyl cyclase-mediated toxicity of pyroglutamate-beta amyloid induces
      striatal neurodegeneration.
AB  - BACKGROUND: Posttranslational modifications of beta amyloid (Abeta) have been
      shown to affect its biophysical and neurophysiological properties. One of these
      modifications is N-terminal pyroglutamate (pE) formation. Enzymatic glutaminyl
      cyclase (QC) activity catalyzes cyclization of truncated Abeta(3-x), generating
      pE3-Abeta. Compared to unmodified Abeta, pE3-Abeta is more hydrophobic and
      neurotoxic. In addition, it accelerates aggregation of other Abeta species. To
      directly investigate pE3-Abeta formation and toxicity in vivo, transgenic (tg)
      ETNA (E at the truncated N-terminus of Abeta) mice expressing truncated human
      Abeta(3-42) were generated and comprehensively characterized. To further
      investigate the role of QC in pE3-Abeta formation in vivo, ETNA mice were
      intercrossed with tg mice overexpressing human QC (hQC) to generate double tg
      ETNA-hQC mice. RESULTS: Expression of truncated Abeta(3-42) was detected mainly
      in the lateral striatum of ETNA mice, leading to progressive accumulation of pE3
      Abeta. This ultimately resulted in astrocytosis, loss of DARPP-32
      immunoreactivity, and neuronal loss at the sites of pE3-Abeta formation.
      Neuropathology in ETNA mice was associated with behavioral alterations. In
      particular, hyperactivity and impaired acoustic sensorimotor gating were
      detected. Double tg ETNA-hQC mice showed similar Abeta levels and expression
      sites, while pE3-Abeta were significantly increased, entailing increased
      astrocytosis and neuronal loss. CONCLUSIONS: ETNA and ETNA-hQC mice represent
      novel mouse models for QC-mediated toxicity of truncated and pE-modified Abeta.
      Due to their significant striatal neurodegeneration these mice can also be used
      for analysis of striatal regulation of basal locomotor activity and sensorimotor
      gating, and possibly for DARPP-32-dependent neurophysiology and neuropathology.
      The spatio-temporal correlation of pE3-Abeta and neuropathology strongly argues
      for an important role of this Abeta species in neurodegenerative processes in
      these models.

PMID- 24083639
TI  - Variations in bitter-taste receptor genes, dietary intake, and colorectal adenoma
      risk.
AB  - Genetic variants in bitter-taste receptor genes have been hypothesized to
      negatively impact health outcomes and/or influence dietary intake and,
      consequently, could increase the risk of colorectal neoplasia. Using a case
      control study of 914 colorectal adenoma cases/1188 controls, we explored
      associations among colorectal adenoma risk, dietary intake, and genetic variation
      in 3 bitter-taste receptor genes: TAS2R38 (rs713598, rs1726866, rs10246939),
      TAS2R16 (rs846672), and TAS2R50 (rs1376251). Analysis of covariance was conducted
      to detect trends in dietary intake across TAS2R genotypes/haplotypes. Odds ratios
      and 95% confidence intervals were estimated by logistic regression to test gene
      adenoma risk associations. No significant associations were observed between the
      TAS2R38 PAV/PAV diplotype or the TAS2R16 (rs846672) polymorphism with the
      selected diet variables. We observed weak inverse associations between the
      TAS2R50 (rs1376251) C allele and dietary fiber and vegetable intake (Ps < 0.015).
      Odds ratios for adenoma risk were not significantly different from the null. Our
      findings do not support a link between these TAS2R genotypes/haplotypes and
      dietary intake that could impact colorectal adenoma risk. However, given the
      paucity of data, we cannot dismiss the possibility that these genes may influence
      colorectal adenoma risk in other ways, such as through impaired gastrointestinal
      function, particularly in subgroups of the population. 

PMID- 24083640
TI  - Copper-mediated amidation of alkenylzirconocenes with acyl azides: formation of
      enamides.
AB  - Copper-mediated amidation of alkenylzirconocenes generated in situ from alkynes
      and zirconocenes with acyl azides is accomplished under mild conditions. The
      reaction can be used to prepare various enamides. 

PMID- 24083641
TI  - Delivering healthcare in an environment of poverty and exclusion: a lesson from
      the base of the pyramid.

PMID- 24083642
TI  - Anxiety, anger, and mortality risk among survivors of myocardial infarction.
AB  - BACKGROUND: Although there is evidence that anxiety and anger are associated with
      a higher risk of cardiovascular events, studies examining the relationship
      between these stressors and prognosis following myocardial infarction have been
      mixed. METHODS: We conducted a prospective cohort study of 1968 participants
      (average age 60.2 years, 30.6% women) in the Determinants of Myocardial
      Infarction Onset Study recruited at the time of admission for myocardial
      infarction between 1989 and 1996. We used the state anxiety and anger subscales
      of the State-Trait Personality Inventory. Participants were followed for all
      cause mortality through December 31, 2007 using the National Death Index. We
      constructed multivariable Cox proportional hazards models adjusted for
      demographic, behavioral, and clinical confounders and calculated hazard ratios
      (HR) and 95% confidence intervals (CI) to examine the relationship between high
      levels of anxiety and anger and all-cause mortality. RESULTS: Over 10 years of
      follow-up, 525 participants died. Compared with those scoring lower, an anxiety
      score >90(th) percentile was associated with a 1.31-times (95% CI, 0.93-1.84)
      higher mortality rate. The association was apparent in the first 3 years (HR
      1.78; 95% CI 1.08-2.93), but not thereafter. Likewise, an anger score >90(th)
      percentile was associated with a 1.25-times (95% CI, 0.87-1.80) higher mortality
      rate. The association was higher in the first 3 years (HR 1.58; 95% CI, 0.91
      2.74) than in subsequent years, but it was not statistically significant during
      either follow-up period. CONCLUSIONS: In this study of myocardial infarction
      survivors, a high level of anxiety was associated with all-cause mortality, with
      the strongest association in the first 3 years of follow-up.

PMID- 24083643
TI  - Was treatment the trigger? Mycosis fungoides.

PMID- 24083644
TI  - A B-wildering case of paraplegia: cobalamin deficiency.

PMID- 24083645
TI  - When Occam's razor fails: a case of concomitant carcinoid and sarcoidosis.

PMID- 24083646
TI  - Elevated cardiac troponin T levels in critically ill patients with sepsis.
AB  - BACKGROUND: It is known that troponin elevations have prognostic importance in
      critically ill patients. We examined whether cardiac troponin T elevations are
      independently associated with in-hospital, short-term (30 days), and long-term (3
      years) mortality in intensive care unit (ICU) patients admitted with sepsis,
      severe sepsis, and septic shock after adjusting for the severity of disease with
      the Acute Physiology, Age and Chronic Health Evaluation III system. METHODS: We
      studied the Mayo Clinic's Acute Physiology, Age and Chronic Health Evaluation III
      database and cardiac troponin T levels from patients admitted consecutively to
      the medical ICU. Between January 2001 and December 2006, 926 patients with sepsis
      had cardiac troponin T measured at ICU admission. In-hospital, short-term, and
      long-term all-cause mortality were determined. RESULTS: Among study patients, 645
      (69.7%) had elevated cardiac troponin T levels and 281 (30.3%) had undetectable
      cardiac troponin T. During hospitalization, 15% of the patients with troponin T
      <0.01 ng/mL died compared with 31.9% of those with troponin T >= 0.01 ng/mL (P <
      .0001). At 30 days, mortality was 31% and 17% in patients with and without
      elevations, respectively (P < .0001). The Kaplan-Meier probability of survival at
      1-, 2-, and 3-year follow-ups was 68.1%, 56.3%, and 46.8% with troponin T >= 0.01
      ng/mL, respectively, and 76.4%, 69.1%, and 62.0% with troponin T <0.01 MUg/L,
      respectively (P < .0001). After adjustment for severity of disease and baseline
      characteristics, cardiac troponin T levels remained associated with in-hospital
      and short-term mortality but not with long-term mortality. CONCLUSIONS: In
      patients with sepsis who are admitted to an ICU, cardiac troponin T elevations
      are independently associated with in-hospital and short-term mortality but not
      long-term mortality.

PMID- 24083647
TI  - Quenching of excited triplet states by dissolved natural organic matter.
AB  - Excited triplet states of aromatic ketones and quinones are used as proxies to
      assess the reactivity of excited triplet states of the dissolved organic matter
      ((3)DOM*) in natural waters. (3)DOM* are crucial transients in environmental
      photochemistry responsible for contaminant transformation, production of reactive
      oxygen species, and potentially photobleaching of DOM. In recent photochemical
      studies aimed at clarifying the role of DOM as an inhibitor of triplet-induced
      oxidations of organic contaminants, aromatic ketones have been used in the
      presence of DOM, and the question of a possible interaction between their excited
      triplet states and DOM has emerged. To clarify this issue, time-resolved laser
      spectroscopy was applied to measure the excited triplet state quenching of four
      different model triplet photosensitizers induced by a suite of DOM from various
      aquatic and terrestrial sources. While no quenching for the anionic triplet
      sensitizers 4-carboxybenzophenone (CBBP) and 9,10-anthraquinone-2,6-disulfonic
      acid (2,6-AQDS) was detected, second-order quenching rate constants with DOM for
      the triplets of 2-acetonaphthone (2AN) and 3-methoxyacetophenone (3MAP) in the
      range of 1.30-3.85 * 10(7) L mol(C)(-1) s(-1) were determined. On the basis of
      the average molecular weight of DOM molecules, the quenching for these uncharged
      excited triplet molecules is nearly diffusion-controlled, but significant
      quenching (>10%) in aerated water is not expected to occur below DOM
      concentrations of 22-72 mg(C) L(-1).

PMID- 24083649
TI  - Externally triggered dual function of complex microcapsules.
AB  - By introducing UV-sensitive chemical groups causing different potential response
      as building blocks, fabricated LbL capsules can be endowed with dual UV
      responsive properties in specific layers. One block is responsible for fast
      capsule sealing and the other for longer term capsule swelling and rupture.
      Therefore, the multifunction of these capsules could be activated selectively
      when exposed to external UV light with suitable wavelengths. In this work, dual
      functional complex microcapsules (PDADMAC/PAZO)4-(DAR/Nafion)2 containing both
      diazonium and aozbenzene groups were proposed as clear examples to realize a time
      dependent UV response for successive encapsulation and release. Upon exposure to
      UV light, the DAR/Nafion layers underwent a rapid in situ cross-linking and hence
      to seal the capsule shells through diazonium-related photolysis. Then further
      gradual shell swelling was followed by realignment of azobenzene molecules in
      PDADMAC/PAZO layers. Fluorescent polymers were consequently studied as cargo
      substances. Results indicated that continuous UV light triggered rapid cargo
      encapsulation over minutes time scale and gradual release with continuous
      irradiation over hours. 

PMID- 24083650
TI  - Early structural changes during spontaneous closure of idiopathic full-thickness
      macular hole determined by optical coherence tomography: a case report.
AB  - BACKGROUND: Spontaneous closure of an idiopathic full-thickness macular hole has
      been reported to occasionally occur. However, the cells involved in plugging the
      macular hole have not been determined conclusively. We aimed to report the early
      structural changes that occur during a spontaneous closure of an idiopathic full
      thickness macular hole determined by spectral-domain optical coherence
      tomography. CASE PRESENTATION: A 71-year-old Japanese man with an idiopathic full
      thickness macular hole and subclinical posterior vitreous detachment in the left
      eye was followed. Three weeks after the identification of the macular hole,
      optical coherence tomography showed tissue that protruded from the interior wall
      of the macular hole at the level of the external limiting membrane toward the
      center of the macular hole. Five months after the first examination, he returned
      with improvements of his visual symptoms, and the macular hole was closed by a
      thin retinal tissue which included the restored external limiting membrane that
      bridged across the macular hole. However, the inner segment/outer segment
      junction line was not intact and the fovea was detached. Two months later,
      optical coherence tomography showed an almost normal foveal configuration with an
      essentially restored inner segment/outer segment junction line and foveal
      reattachment. CONCLUSION: Our results suggest that Muller cells proliferate
      and/or extend at the level of the end of the external limiting membrane to form a
      tissue bridge across the macular hole associated with the external limiting
      membrane restoration first of all. This leads to the adhesion of other retinal
      layers and resolution of the foveal detachment.

PMID- 24083651
TI  - Factors associated with palliative withdrawal of mechanical ventilation and time
      to death after withdrawal.
AB  - BACKGROUND: In imminently dying patients, mechanical ventilation withdrawal is
      often a comfort measure and avoids prolonging the dying process. OBJECTIVE: The
      aim of the study was to identify factors associated with palliative withdrawal of
      mechanical ventilation and time to death after extubation. METHODS: Logistic
      regression models were used to identify factors associated with palliative
      withdrawal of mechanical ventilation. Cox proportional hazards models were used
      to determine factors associated with time to death after extubation. We
      retrospectively evaluated 322 patients who died on mechanical ventilation or
      after palliative ventilator withdrawal at a single tertiary care center. RESULTS:
      Of the 322 ventilated deaths, 159 patients had palliative withdrawal of
      mechanical ventilation and 163 patients died on the ventilator. Clinical service
      was associated with palliative withdrawal of mechanical ventilation: Patients
      withdrawn from the ventilator were less likely to be on the surgery service and
      more likely to be on the neurology/neurosurgical service. The median time to
      death was 0.9 hours (range 0-165 hours). Fraction of inspired oxygen (FIO2)
      greater than 70% (hazard ratio [HR] 1.92, 95% confidence interval [CI ]1.24-2.99)
      and a requirement for vasopressors (HR 2.06, 95% CI 1.38-3.09) were associated
      with shorter time to death. Being on the neurology/neurosurgical service at the
      time of ventilator withdrawal was associated with a longer time to death (HR
      0.60, 95% CI 0.39-0.92). CONCLUSIONS: Palliative withdrawal of mechanical
      ventilation was performed in only half of dying mechanically ventilated patients.
      Because clinical service rather than physiologic parameters are associated with
      withdrawal, targeted interventions may improve withdrawal decisions. Considering
      FIO2 and vasopressor requirements may facilitate counseling families about
      anticipated time to death.

PMID- 24083653
TI  - The emotional and spiritual well-being of hospice patients in Botswana and
      sources of distress for their caregivers.
AB  - BACKGROUND: Little regional data exists on the distress of people nearing the end
      of their lives and their caregivers. OBJECTIVE: The purpose of this study was to
      describe the quality of life and the emotional and spiritual well-being of people
      at the end of life and the sources of distress for their primary caregivers in
      Gaborone, Botswana, in order to inform further development of hospice services.
      DESIGN: This study employed a mixed-methods design. SETTING/SUBJECTS: Twenty
      eight primary caregivers who cared for an adult who passed away fewer than 14
      months prior to the interview date and in the care of a nongovernmental hospice
      in Botswana were interviewed between June and August 2012. MEASUREMENTS:
      Semistructured interviews and the Quality of Death and Dying questionnaire (QODD)
      were used. Quantitative descriptive analysis and qualitative content analysis
      were performed. RESULTS: Quality of life of decedents was poor. Emotional and
      spiritual distress persist at high rates even for those receiving support from a
      nongovernmental hospice (NGH). Caregiver distress arises from practical needs,
      including lack of food, clothing, and shelter, the need for assistance physically
      caring for their loved one, and from emotional and spiritual concerns.
      CONCLUSIONS: The practical, physical, emotional, and spiritual needs of people at
      the end of life in Botswana and their caregivers are not being fully met, with
      poor overall quality of life among the dying. More research is needed to explore
      how hospice and home health services and the services of spiritual leaders can be
      expanded to meet their needs.

PMID- 24083655
TI  - Contemporary treatment of immune thrombocytopenia.
AB  - Immune thrombocytopenia is an autoimmune-mediated disorder and the treatment
      strategies were directed mainly to suppression of the immune system or to removal
      of the spleen as a place of thrombocyte destruction. In last years, it was shown
      that other mechanisms are responsible for development of immune thrombocytopenia:
      reduced thrombocyte lifespan and ineffective marrow platelet production. New
      treatment strategies, such as thrombopoietin receptor agonists, were developed to
      overcome this mechanism. Still there are a difficult minority of patients
      unresponsive to multiple treatments, whose have severe bleeding and another group
      of patients with extensive morbidity from therapy, not restricted to steroids. In
      this review, focused on adult patients, we discuss newer results of therapies and
      consider newer treatment strategies.

PMID- 24083654
TI  - Rapid access to spirocyclic oxindole alkaloids: application of the asymmetric
      palladium-catalyzed [3 + 2] trimethylenemethane cycloaddition.
AB  - The marcfortines are complex secondary metabolites that show potent anthelmintic
      activity and are characterized by the presence of a bicyclo[2.2.2]diazaoctane
      fused to a spirooxindole. Herein, we report the synthesis of two members of this
      family. The synthesis of marcfortine B utilizes a carboxylative TMM cycloaddition
      to establish the spirocyclic core, followed by an intramolecular Michael addition
      and oxidative radical cyclization to access the strained bicyclic ring system. In
      addition, the first asymmetric synthesis of (-)-marcfortine C is described. The
      key step involves a cyano-substituted TMM cycloaddition, which proceeds in nearly
      quantitative yield with high diastereo- and enantioselectivity. The resulting
      chiral center was used to establish all remaining stereocenters in the natural
      product.

PMID- 24083656
TI  - Substrate-based fragment identification for the development of selective,
      nonpeptidic inhibitors of striatal-enriched protein tyrosine phosphatase.
AB  - High levels of striatal-enriched protein tyrosine phosphatase (STEP) activity are
      observed in a number of neuropsychiatric disorders such as Alzheimer's disease.
      Overexpression of STEP results in the dephosphorylation and inactivation of many
      key neuronal signaling molecules, including ionotropic glutamate receptors.
      Moreover, genetically reducing STEP levels in AD mouse models significantly
      reversed cognitive deficits and decreased glutamate receptor internalization.
      These results support STEP as a potential target for drug discovery for the
      treatment of Alzheimer's disease. Herein, a substrate-based approach for the
      discovery and optimization of fragments called substrate activity screening (SAS)
      has been applied to the development of low molecular weight (<450 Da) and
      nonpeptidic, single-digit micromolar mechanism-based STEP inhibitors with greater
      than 20-fold selectivity across multiple tyrosine and dual specificity
      phosphatases. Significant levels of STEP inhibition in rat cortical neurons are
      also observed. 

PMID- 24083658
TI  - Preparation and characterization of decyl-terminated silicon nanoparticles
      encapsulated in lipid nanocapsules.
AB  - In this Article, we report on the encapsulation of decyl-modified silicon
      nanoparticles (decyl-SiNPs) into ~80 nm lipid nanocapsules (LNCs). The decyl
      SiNPs were produced by thermal hydrosilylation of hydride-terminated SiNPs (H
      SiNPs) liberated from porous silicon. Various techniques, including Fourier
      transform infrared spectroscopy (FT-IR), transmission electron microscopy (TEM),
      UV-vis absorption, dynamic light scattering (DLS), and photoluminescence (PL),
      were used to characterize their size, shape, colloidal, and optical properties.
      The results indicate that these nanocapsules feature controllable size, good
      dispersity, high loading rate of SiNPs, colloidal stability in various media, and
      bright PL. The PL of decyl-SiNPs loaded LNCs was stable upon heating to 80 
      degrees C, but was sensitive to basic solutions due to proton-gated emission of
      the SiNPs arranged at the LNCs interface between the oil phase and the
      hydrophilic polyethylene glycol moieties of the surfactant. These luminescent
      nanocapsules are therefore promising candidates as cellular probes for
      fluorescence imaging. In addition, it was found that TEM imaging of small-sized
      decyl-SiNPs could be greatly improved by preliminary negative staining of TEM
      grids with phosphotungstic acid. 

PMID- 24083659
TI  - Effective in-service training design and delivery: evidence from an integrative
      literature review.
AB  - BACKGROUND: In-service training represents a significant financial investment for
      supporting continued competence of the health care workforce. An integrative
      review of the education and training literature was conducted to identify
      effective training approaches for health worker continuing professional education
      (CPE) and what evidence exists of outcomes derived from CPE. METHODS: A
      literature review was conducted from multiple databases including PubMed, the
      Cochrane Library and Cumulative Index to Nursing and Allied Health Literature
      (CINAHL) between May and June 2011. The initial review of titles and abstracts
      produced 244 results. Articles selected for analysis after two quality reviews
      consisted of systematic reviews, randomized controlled trials (RCTs) and
      programme evaluations published in peer-reviewed journals from 2000 to 2011 in
      the English language. The articles analysed included 37 systematic reviews and 32
      RCTs. The research questions focused on the evidence supporting educational
      techniques, frequency, setting and media used to deliver instruction for
      continuing health professional education. RESULTS: The evidence suggests the use
      of multiple techniques that allow for interaction and enable learners to process
      and apply information. Case-based learning, clinical simulations, practice and
      feedback are identified as effective educational techniques. Didactic techniques
      that involve passive instruction, such as reading or lecture, have been found to
      have little or no impact on learning outcomes. Repetitive interventions, rather
      than single interventions, were shown to be superior for learning outcomes.
      Settings similar to the workplace improved skill acquisition and performance.
      Computer-based learning can be equally or more effective than live instruction
      and more cost efficient if effective techniques are used. Effective techniques
      can lead to improvements in knowledge and skill outcomes and clinical practice
      behaviours, but there is less evidence directly linking CPE to improved clinical
      outcomes. Very limited quality data are available from low- to middle-income
      countries. CONCLUSIONS: Educational techniques are critical to learning outcomes.
      Targeted, repetitive interventions can result in better learning outcomes.
      Setting should be selected to support relevant and realistic practice and
      increase efficiency. Media should be selected based on the potential to support
      effective educational techniques and efficiency of instruction. CPE can lead to
      improved learning outcomes if effective techniques are used. Limited data
      indicate that there may also be an effect on improving clinical practice
      behaviours. The research agenda calls for well-constructed evaluations of
      culturally appropriate combinations of technique, setting, frequency and media,
      developed for and tested among all levels of health workers in low- and middle
      income countries.

PMID- 24083661
TI  - The study of epilepsy in the Netherlands in the nineteenth century.
AB  - In the nineteenth century, there was a continuous debate on the structure and
      function of the brain, focusing on localization of function and on epilepsy.
      France, Germany, and England played a leading role. This article addresses the
      question of what happened with respect to the study of epilepsy in the
      Netherlands in that period. A systematic search of the literature has been
      performed and papers by Schroeder van der Kolk, Huet, Jelgersma, and Niermeijer
      are discussed. Also two dissertations were selected for discussion, those of
      Kroon and Langelaan. It is concluded that from a scientific point of view, only
      the paper by Schroeder van der Kolk deserved and received international
      attention. 

PMID- 24083660
TI  - Predictive factors of achieving therapeutic goals of hypertriglyceridemia.
AB  - OBJECTIVES: The aim of this study was to ascertain the factors associated with
      non-achievement of triglyceride (TG) goals in a cohort of hypertriglyceridemic
      patients attending the lipid clinics of the Spanish Arteriosclerosis Society (LC
      SAS). METHODS: Patients with high TG levels (>2.2 mmol/L; 200 mg/dL) were
      included in this multicenter, prospective, observational study and followed up
      for 1 year. The TG goal was <=2.2 mmol/L (200 mg/dL). Main limitations of this
      study are that etiologic diagnosis of hypertriglyceridemia was not done under
      unified criteria and drug compliance was not evaluated. RESULTS: From 1394
      patients initially included in the study, 929 (age range: 50 +/- 12 years, 26%
      women) were followed up for 1 year; 523 patients (56%) failed to reach the TG
      target. These patients were younger, had a higher body mass index (BMI), were
      more frequently smokers, hypertensive and diabetic and had more severe
      dyslipidemia. They were also more sedentary, their diet was of poorer quality and
      they had higher alcohol consumption. The independent predictors of treatment
      failure were hypertriglyceridemia severity, low high density lipoprotein
      cholesterol (HDL-C), and high non-HDL-C, alcohol consumption and a raised BMI,
      while drug treatment had no predictive power. CONCLUSION: Independent predictors
      of failure to achieve hypertriglyceridemia treatment goals are inappropriate
      lifestyle, evidenced by insufficient weight loss, alcohol consumption and
      dyslipidemia severity.

PMID- 24083662
TI  - Simultaneous interpenetrating silicone hydrogel based on radical/addition
      polymerization for extended release of ocular therapeutics.
AB  - Hydrogels with interpenetrating network (IPN) can overcome thermodynamic
      incompatibility and obtain transparent materials with limited phase separation.
      In this report, hydroxyl-grafting polysiloxane (HPSO) was synthesized and
      transparent silicone hydrogels with interpenetrating network were simultaneously
      prepared based on radical polymerization of methacrylic monomer of 3
      methacryloxypropyl tris(trimethylsiloxy)silane/N,N-dimethylacrylamide and
      addition polymerization of HPSO/isophorone diisocyanate. The silicone hydrogels
      were characterized by dehydration kinetics, tensile tester, light transmittance,
      ion permeability, oxygen permeability, and lysozyme deposition. The results show
      that increasing the proportion of hydrophobic network of HPSO in the IPN silicone
      hydrogel decreases equilibrium swelling ratio, ion permeability, Young's modulus,
      and lysozyme deposition; on the contrary, increased tensile strength, elongation
      at break and oxygen permeability. Puerarin and ketoconazole were used as models
      to evaluate the drug loading and in vitro release behavior of the silicone
      hydrogels. It is revealed that the amount of loaded drugs in the hydrogel
      decreases with the increase of HPSO network in the hydrogels. All the silicone
      hydrogels exhibit extended release behavior, especially for ketoconazole, the in
      vitro release is divided into two phases corresponding to the rapid release at
      initial 24 h and relatively slow release from 125 to 360 h.

PMID- 24083663
TI  - Acceptance of selective contracting: the role of trust in the health insurer.
AB  - BACKGROUND: In a demand oriented health care system based on managed competition,
      health insurers have incentives to become prudent buyers of care on behalf of
      their enrolees. They are allowed to selectively contract care providers. This is
      supposed to stimulate competition between care providers and both increase the
      quality of care and contain costs in the health care system. However, health
      insurers are reluctant to implement selective contracting; they believe their
      enrolees will not accept this. One reason, insurers believe, is that enrolees do
      not trust their health insurer. However, this has never been studied. This paper
      aims to study the role played by enrolees' trust in the health insurer on their
      acceptance of selective contracting. METHODS: An online survey was conducted
      among 4,422 people insured through a large Dutch health insurance company. Trust
      in the health insurer, trust in the purchasing strategy of the health insurer and
      acceptance of selective contracting were measured using multiple item scales. A
      regression model was constructed to analyse the results. RESULTS: Trust in the
      health insurer turned out to be an important prerequisite for the acceptance of
      selective contracting among their enrolees. The association of trust in the
      purchasing strategy of the health insurer with acceptance of selective
      contracting is stronger for older people than younger people. Furthermore, it was
      found that men and healthier people accepted selective contracting by their
      health insurer more readily. This was also true for younger people with a low
      level of trust in their health insurer. CONCLUSION: This study provides insight
      into factors that influence people's acceptance of selective contracting by their
      health insurer. This may help health insurers to implement selective contracting
      in a way their enrolees will accept and, thus, help systems of managed
      competition to develop.

PMID- 24083664
TI  - The biomechanical properties of the cornea and anterior segment parameters.
AB  - BACKGROUND: To investigate the biomechanical properties of the cornea measured
      with the Ocular Response Analyzer (ORA) and their association with the anterior
      segment parameters representing the geometric dimensions including the corneal
      volume and anterior chamber volume. METHODS: A retrospective review of 1020
      patients who visited the BGN Eye Clinic was done. The mean radius of the corneal
      curvature, corneal astigmatism, corneal volume, anterior chamber depth, and
      anterior chamber volume were measured with an anterior segment tomographer. The
      central corneal thickness (CCT) was measured with an ultrasonic pachymeter. The
      corneal diameter was measured with an Orbscan as White to White. Cornea
      hysteresis (CH), corneal resistance factor (CRF), Goldmann correlated intraocular
      pressure (IOPg), and cornea-compensated IOP (IOPcc) were measured with an ORA.
      Multiple linear regression models were constructed with CH and CRF as the
      dependent variables and age, gender, and the anterior segment parameters as the
      covariates. RESULTS: 958 eyes from 958 patients (mean age 26.7 years; male 43.4%)
      were included in this study after excluding some eyes according to the exclusion
      criteria. The mean CH and CRF were 10.1 and 9.9 mmHg, respectively. The mean IOPg
      and IOPcc were 14.8 and 15.8 mmHg. The multivariate analysis showed that CH was
      negatively associated with the mean radius of the cornea curvature (regression
      coefficient = -0.481, p = 0.023) and positively associated with CCT (regression
      coefficient = 0.015, p < 0.001) and corneal volume (regression coefficient
      =0.059, p = 0.014). The association between CH and the corneal diameter, anterior
      chamber depth, and anterior chamber volume were not statistically significant.
      The evaluation of CRF showed that CRF was negatively associated with the mean
      radius of the cornea curvature (regression coefficient = -0.540, p = 0.013), and
      positively associated with CCT (beta = 0.026, p < 0.001). The association between
      CRF and the corneal diameter, corneal volume, anterior chamber depth, and
      anterior chamber volume were not statistically significant. CONCLUSION: The CH
      was shown to be positively associated with the corneal volume and the association
      between CH and the anterior chamber volume were not significant. The associations
      of CRF with the corneal volume or anterior chamber volume were not significant.

PMID- 24083666
TI  - Under the right conditions: protecting podocytes from diabetes-induced damage.
AB  - Hyperglycemia-induced damage to the glomerular podocyte is thought to be a
      critical early event in diabetic nephropathy. Interventions that prevent podocyte
      damage or loss have been shown to have potential for the treatment of diabetic
      nephropathy. New data show that conditioned medium from adipocyte-derived
      mesenchymal stem cells has the potential to protect podocytes from high-glucose
      induced damage. Furthermore, epidermal growth factor may be the critical
      ingredient mediating this effect. These data suggest that components of the
      conditioned medium of mesenchymal stem cells, in addition to the cells
      themselves, may have potential for the treatment of diseases such as diabetic
      nephropathy.

PMID- 24083665
TI  - Ultralow concentrations of bupivacaine exert anti-inflammatory effects on
      inflammation-reactive astrocytes.
AB  - Bupivacaine is a widely used, local anesthetic agent that blocks voltage-gated
      Na(+) channels when used for neuro-axial blockades. Much lower concentrations of
      bupivacaine than in normal clinical use, < 10(-8)  m, evoked Ca(2+) transients in
      astrocytes from rat cerebral cortex, that were inositol trisphosphate receptor
      dependent. We investigated whether bupivacaine exerts an influence on the Ca(2+)
      signaling and interleukin-1beta (IL-1beta) secretion in inflammation-reactive
      astrocytes when used at ultralow concentrations, < 10(-8)  m. Furthermore, we
      wanted to determine if bupivacaine interacts with the opioid-, 5
      hydroxytryptamine- (5-HT) and glutamate-receptor systems. With respect to the MU
      opioid- and 5-HT-receptor systems, bupivacaine restored the inflammation-reactive
      astrocytes to their normal non-inflammatory levels. With respect to the glutamate
      receptor system, bupivacaine, in combination with an ultralow concentration of
      the MU-opioid receptor antagonist naloxone and MU-opioid receptor agonists,
      restored the inflammation-reactive astrocytes to their normal non-inflammatory
      levels. Ultralow concentrations of bupivacaine attenuated the inflammation
      induced upregulation of IL-1beta secretion. The results indicate that bupivacaine
      interacts with the opioid-, 5-HT- and glutamate-receptor systems by affecting
      Ca(2+) signaling and IL-1beta release in inflammation-reactive astrocytes. These
      results suggest that bupivacaine may be used at ultralow concentrations as an
      anti-inflammatory drug, either alone or in combination with opioid agonists and
      ultralow concentrations of an opioid antagonist. 

PMID- 24083667
TI  - Iron-catalyzed ring-opening azidation and allylation of O-heterocycles.
AB  - We have established the first catalytic C-C and C-N bond formation reactions of O
      heterocycles (e.g., tetrahydrofuran, phthalane, and lactone derivatives) using
      iron trichloride as a catalyst in the presence of TMSN3 or allylsilanes
      accompanied by the ring opening of O-heterocycles. The reactions smoothly
      proceeded at room temperature to give the corresponding primary saturated
      alcohols from the 2-substituted tetrahydrofurans, ortho-substituted benzyl
      alcohols from phthalanes, and saturated carboxylic acids from lactones in high
      yields. 

PMID- 24083669
TI  - Effect of ursolic acid on MAPK in cyclin D1 signaling and RING-type E3 ligase
      (SCF E3s) in two endometrial cancer cell lines.
AB  - Cyclin D1 regulates G1 progression and is important in the development and
      proliferation of various human cancers. Cyclin D1 gene expression is activated by
      the Ras kinase cascade. Nuclear cyclin D1 levels are dependent on cytoplasmic
      degradation of cyclin D1 via ubiquitin-mediated proteolysis. We sought to
      determine whether the important MAPK signaling pathway, in the cyclin D1 cascade,
      including FBXW8, Cullin1, and the ubiquitination pathway mediated these effects.
      Ursolic acid (UA) treatment of SNG-2 cells, an endometrial cancer cell line,
      decreased cyclin D1, pERK1/2, FBXW8, and Cullin1 levels in a dose- and time
      dependent manner. RING-type E3 ligase consists of CulIin1, Rbx, Skp1, and a
      member of the F-box protein family. In SNG-2, both dose- and time-dependent
      inhibition of Rbx 1 were observed following treatment with UA. Moreover, in
      HEC108 cells, another endometrial cancer cell line, UA treatment decreased cyclin
      D1, pERK1/2, and Cullin1 levels in a dose- and time-dependent manner and UA
      markedly inhibited FBXW8. Treatment of HEC108 cells moderately decreased Rbx1 in
      a dose- and-time-dependent fashion. In contrast, UA treatment increased
      ubiquitinated proteins in a dose- and time-dependent manner in both cell lines.
      RING-type E3 ligase accumulated in the cytoplasm following UA treatment of SNG
      2cells. That in turn prevented cytoplasmic degradation of cyclin D1 via RING-type
      E3 (SCF E3s) ligase. In conclusion, our study found inhibition of the MAPK-
      cyclin D1 pathway and RING type E3 ligase (SCF E3s) in both endometrial cancer
      cell lines. Furthermore, CD36 was noted as a cell surface receptor for UA. 

PMID- 24083668
TI  - Brain activity and medical diagnosis: an EEG study.
AB  - BACKGROUND: Despite new brain imaging techniques that have improved the study of
      the underlying processes of human decision-making, to the best of our knowledge,
      there have been very few studies that have attempted to investigate brain
      activity during medical diagnostic processing. We investigated brain
      electroencephalography (EEG) activity associated with diagnostic decision-making
      in the realm of veterinary medicine using X-rays as a fundamental auxiliary test.
      EEG signals were analysed using Principal Components (PCA) and Logistic
      Regression Analysis RESULTS: The principal component analysis revealed three
      patterns that accounted for 85% of the total variance in the EEG activity
      recorded while veterinary doctors read a clinical history, examined an X-ray
      image pertinent to a medical case, and selected among alternative diagnostic
      hypotheses. Two of these patterns are proposed to be associated with visual
      processing and the executive control of the task. The other two patterns are
      proposed to be related to the reasoning process that occurs during diagnostic
      decision-making. CONCLUSIONS: PCA analysis was successful in disclosing the
      different patterns of brain activity associated with hypothesis triggering and
      handling (pattern P1); identification uncertainty and prevalence assessment
      (pattern P3), and hypothesis plausibility calculation (pattern P2); Logistic
      regression analysis was successful in disclosing the brain activity associated
      with clinical reasoning success, and together with regression analysis showed
      that clinical practice reorganizes the neural circuits supporting clinical
      reasoning.

PMID- 24083671
TI  - PM10 and PM2.5 and health risk assessment for heavy metals in a typical factory
      for cathode ray tube television recycling.
AB  - The representative waste television recycling process was chosen as the object of
      this study, including manual dismantling and mechanical separation of printed
      circuit boards (PCBs) and cathode ray tubes (CRTs) in two independent workshops.
      During these recycling processes, fine particulate matter and heavy metals will
      be released into the air to impact the environment and the health of the workers.
      The mass concentrations of PM2.5 (particles below 2.5 MUm diameter) in mechanical
      and dismantling workshops ranged from 252.6 to 290.8 MUg/m(3) and from 112.7 to
      169.4 MUg/m(3), respectively. The average concentration of PM2.5 around the
      workshop was 98.5 MUg/m(3). Meanwhile, the contents of PM10 (particles below 10
      MUm diameter) were all below the risk threshold, except that (360.4 MUg/m(3))
      monitored in the mechanical workshop. In two workshops, Pb (20.46 and 6.935 mg/g)
      was the most enriched metal in the PM2.5 samples, while in PM10, the
      concentration of Cu (27.76 and 31.80 mg/g) was the largest. The concentration of
      Cd was the least in both PM10 and PM2.5. Health risk assessment showed that the
      total hazard indexes for non-carcinogenic metal in PM2.5 monitored in mechanical
      and dismantling workshops and in the southeast of the workshops were 7.61, 3.01,
      and 1.57, respectively, all above the safety level. Furthermore, Pb (7.28 and
      3.01) might possibly have a non-carcinogenic effect on the workers in two
      workshops, and the sequence of the hazard quotient (HQ) through the three
      exposure ways was ingestion > dermal contact > inhalation. The lifetime cancer
      risk of four targeted metals was Cr > Ni > Pb > Cd, which could be proven in all
      monitoring samples. This study aims to provide a large amount of valid data for
      the State Environmental Protection Department to develop relevant environmental
      standards and for companies to improve the waste television recycling system to
      be more efficiently and environmentally friendly. 

PMID- 24083670
TI  - Intravenous transplantation of mesenchymal stem cells preconditioned with early
      phase stroke serum: current evidence and study protocol for a randomized trial.
AB  - BACKGROUND: Recovery after a major stroke is usually limited, but cell therapy
      for patients with fixed neurologic deficits is emerging. Several recent clinical
      trials have investigated mesenchymal stem cell (MSC) therapy for patients with
      ischemic stroke. We previously reported the results of a controlled trial on the
      application of autologous MSCs in patients with ischemic stroke with a long-term
      follow-up of up to 5 years (the 'STem cell Application Researches and Trials In
      NeuroloGy' (STARTING) study). The results from this pilot trial are challenging,
      but also raise important issues. In addition, there have been recent efforts to
      improve the safety and efficacy of MSC therapy for stroke. METHODS AND DESIGN:
      The clinical and preclinical background and the STARTING-2 study protocol are
      provided. The trial is a prospective, randomized, open-label, blinded-endpoint
      (PROBE) clinical trial. Both acute and chronic stroke patients will be selected
      based on clinical and radiological features and followed for 3 months after MSC
      treatment. The subjects will be randomized into one of two groups: (A) a MSC
      group (n = 40) or (B) a control group (n = 20). Autologous MSCs will be
      intravenously administered after ex vivo culture expansion with autologous
      ischemic serum obtained as early as possible, to enhance the therapeutic efficacy
      (ischemic preconditioning). Objective outcome measurements will be performed
      using multimodal MRI and detailed functional assessments by blinded observers.
      DISCUSSION: This trial is the first to evaluate the efficacy of MSCs in patients
      with ischemic stroke. The results may provide better evidence for the
      effectiveness of MSC therapy in patients with ischemic stroke. TRIAL
      REGISTRATION: This trial was registered with ClinicalTrials.gov, number
      NCT01716481.

PMID- 24083673
TI  - Organic acid-catalyzed polyurethane formation via a dual-activated mechanism:
      unexpected preference of N-activation over O-activation of isocyanates.
AB  - A systematic study of acid organocatalysts for the polyaddition of poly(ethylene
      glycol) to hexamethylene diisocyanate in solution has been performed. Among
      organic acids evaluated, sulfonic acids were found the most effective for
      urethane formations even when compared with conventional tin-based catalysts
      (dibutyltin dilaurate) or 1,8-diazabicyclo[5.4.0]undec-7-ene. In comparison,
      phosphonic and carboxylic acids showed considerably lower catalytic activities.
      Furthermore, sulfonic acids gave polyurethanes with higher molecular weights than
      was observed using traditional catalyst systems. Molecular modeling was conducted
      to provide mechanistic insight and supported a dual activation mechanism, whereby
      ternary adducts form in the presence of acid and engender both electrophilic
      isocyanate activation and nucleophilic alcohol activation through hydrogen
      bonding. Such a mechanism suggests catalytic activity is a function of not only
      acid strength but also inherent conjugate base electron density. 

PMID- 24083672
TI  - Selection and validation of reference genes for gene expression analysis in
      apomictic and sexual Cenchrus ciliaris.
AB  - BACKGROUND: Apomixis is a naturally occurring asexual mode of seed reproduction
      resulting in offspring genetically identical to the maternal plant. Identifying
      differential gene expression patterns between apomictic and sexual plants is
      valuable to help deconstruct the trait. Quantitative RT-PCR (qRT-PCR) is a
      popular method for analyzing gene expression. Normalizing gene expression data
      using proper reference genes which show stable expression under investigated
      conditions is critical in qRT-PCR analysis. We used qRT-PCR to validate
      expression and stability of six potential reference genes (EF1alpha, EIF4A, UBCE,
      GAPDH, ACT2 and TUBA) in vegetative and reproductive tissues of B-2S and B-12-9
      accessions of C. ciliaris. FINDINGS: Among tissue types evaluated, EF1alpha
      showed the highest level of expression while TUBA showed the lowest. When all
      tissue types were evaluated and compared between genotypes, EIF4A was the most
      stable reference gene. Gene expression stability for specific ovary stages of B
      2S and B-12-9 was also determined. Except for TUBA, all other tested reference
      genes could be used for any stage-specific ovary tissue normalization,
      irrespective of the mode of reproduction. CONCLUSION: Our gene expression
      stability assay using six reference genes, in sexual and apomictic accessions of
      C. ciliaris, suggests that EIF4A is the most stable gene across all tissue types
      analyzed. All other tested reference genes, with the exception of TUBA, could be
      used for gene expression comparison studies between sexual and apomictic ovaries
      over multiple developmental stages. This reference gene validation data in C.
      ciliaris will serve as an important base for future apomixis-related
      transcriptome data validation.

PMID- 24083674
TI  - The impact of menopausal symptoms on quality of life, productivity, and economic
      outcomes.
AB  - BACKGROUND: The aim of this study was to investigate the impact of menopausal
      symptoms and menopausal symptom severity on health-related quality of life
      (HRQoL), work impairment, healthcare utilization, and costs. METHODS: Data from
      the 2005 United States National Health and Wellness Survey were used, with only
      women 40-64 years without a history of cancer included in the analyses (N=8,811).
      Women who reported experiencing menopausal symptoms (n=4,116) were compared with
      women not experiencing menopausal symptoms (n=4,695) on HRQoL, work impairment,
      and healthcare utilization using regression modeling (and controlling for
      demographics and health characteristic differences). Additionally, individual
      menopausal symptoms were used as predictors of outcomes in a separate set of
      regression models. RESULTS: The mean age of women in the analysis was 49.8 years
      (standard deviation,+/-5.9). Women experiencing menopausal symptoms reported
      significantly lower levels of HRQoL and significantly higher work impairment, and
      healthcare utilization than women without menopausal symptoms. Depression,
      anxiety, and joint stiffness were symptoms with the strongest associations with
      health outcomes. CONCLUSIONS: Menopausal symptoms can be a significant humanistic
      and economic burden on women in middle age.

PMID- 24083675
TI  - Omega-3 polyunsaturated fatty acids for major depressive disorder.
AB  - INTRODUCTION: Omega-3 polyunsaturated fatty acids (omega-3 PUFAs) are not
      synthesized by the human body; they must be derived from dietary sources and they
      have been known to be involved with neurological, cardiovascular,
      cerebrovascular, autoimmune and metabolic diseases, and cognitive disorder as
      well as mood disorders. AREAS COVERED: A number of epidemiological and
      preclinical studies have proven the potential benefit and critical role of omega
      3 PUFA in the development and management of major depressive disorder (MDD). In
      addition, recently independent clinical trials and meta-analyses have also
      provided superidority of omega-3 PUFA over placebo as monotherapy or augmentation
      agent in the treatment of MDD. This article presents a brief overview of the
      evidence to date about the clinical application and biological mechanisms of
      omega-3 PUFA in the treatment of MDD. EXPERT OPINION: Given the potential action
      mechanism, clinical benefits and currently available clinical trial data, omega-3
      PUFAs may deserve greater attention and wider application for treatment of MDD.
      However, the practical utility of omega-3 PUFA as one of promising alternative
      agent for treatment of MDD still have many questions unresolved to be fully
      addressed in near future.

PMID- 24083676
TI  - Tuning the antibacterial activity of amphiphilic neamine derivatives and
      comparison to paromamine homologues.
AB  - Aminoglycosides are antibiotic drugs that act through binding to rRNA. In the
      search for antimicrobial amphiphilic aminoglycosides targeting bacterial
      membranes, we report here on the discovery of three dialkyl derivatives of the
      small aminoglycoside neamine active against susceptible and resistant Gram
      positive and Gram-negative bacteria. One of these derivatives (R = 2
      naphthylpropyl), which has good activity against MRSA and VRSA, showed a low
      toxicity in eukaryotic cells at 10 MUM. The synthesis of amphiphilic paromamine
      and neamine homologous derivatives pointed out the role of the 6'-amine function
      of the neamine core in the antibacterial effects. The optimal number of
      lipophilic substituents to be attached to the neamine core and the corresponding
      required lipophilicity determined here should permit a more selective targeting
      of bacterial membranes relative to eukaryotic membranes. This work revealed the
      existence of windows of lipophilicity necessary for obtaining strong
      antibacterial effects that should be of interest in the field of antibacterial
      amphiphilic aminoglycosides. 

PMID- 24083677
TI  - Incidence of genitourinary conditions in women with a diagnosis of vulvar/vaginal
      atrophy.
AB  - OBJECTIVES: Vulvar/vaginal atrophy (VVA) is one genitourinary condition
      associated with a decline in estrogen. This may be bothersome for women following
      menopause. Although the clinical features of VVA and other conditions after
      menopause have been documented, few studies have quantified the magnitude of
      association between VVA and other genitourinary conditions. METHODS: A VVA cohort
      was identified from two United States administrative claims databases. A matched
      cohort of an equal number of controls was randomly selected from a pool of women
      40-79 years of age without VVA. Baseline characteristics and medical history were
      tabulated for the VVA cohort and matched controls. Six genitourinary conditions
      ('urinary tract infections', 'other/unspecified genitourinary symptoms', 'other
      inflammatory diseases of female pelvic organs', 'menopausal disorders', 'female
      genital pain and other symptoms', and 'other/unspecified female genital
      disorders') were hypothesized a priori to be associated with VVA. Adjusted
      incidence rate ratios measured the strength of association of VVA with each
      condition. RESULTS: A total of 9080 women aged 40-79 years with newly diagnosed
      VVA during 2000-2010 were identified. The mean age of VVA patients and matched
      controls was 60.2 years. At baseline, a significantly (p < 0.001) higher
      proportion of women in the VVA cohort had a diagnosis of angina, osteoporosis,
      migraines, insomnia, or anxiety, or received estrogen supplementation or
      selective estrogen receptor modulators. VVA patients had a significantly (p <
      0.001) higher incidence of each of the genitourinary conditions compared to
      controls. The condition most strongly associated with VVA with a relative risk of
      6.2 was 'other inflammatory diseases of female pelvic organs'. CONCLUSIONS: Women
      with VVA have a greater risk of genitourinary conditions compared to those
      without. The overall prevalence of VVA and other genitourinary conditions may be
      underreported as claims data only captures information for patients under medical
      care and many women do not seek consultation for VVA symptoms.

PMID- 24083680
TI  - Three twentieth-century multiauthored neurological handbooks--a historical
      analysis and bibliometric comparison.
AB  - The emergence of neurology as a separate specialty from internal medicine and
      psychiatry took several decades, starting at the end of the nineteenth century.
      This can be adequately reconstructed by focusing on the establishment of
      specialized journals, societies, university chairs, the invention and application
      of specific instruments, medical practices, and certainly also the publication of
      pivotal textbooks in the field. Particularly around 1900, the German-speaking
      countries played an integral role in this process. In this article, one aspect is
      extensively explored, notably the publication (in the twentieth century) of three
      comprehensive and influential multivolume and multiauthor handbooks entirely
      devoted to neurology. All available volumes of Max Lewandowsky's Handbuch der
      Neurologie (1910-1914) and the Handbuch der Neurologie (1935-1937) of Oswald
      Bumke and Otfrid Foerster were analyzed. The handbooks were then compared with
      Pierre Vinken's and George Bruyn's Handbook of Clinical Neurology (1968-2002).
      Over the span of nearly a century these publications became ever more
      comprehensive and developed into a global, encompassing project as is reflected
      in the increasing number of foreign authors. Whereas the first two handbooks were
      published mainly in German, "Vinken & Bruyn" was eventually published entirely in
      English, indicating the general changes in the scientific language of neurology
      after World War II. Distinctions include the uniformity of the series, manner of
      editorial involvement, thematic comprehensiveness, inclusion of volume editors in
      "Vinken & Bruyn," and the provision of index volumes. The increasing use of
      authorities in various neurological subspecialties is an important factor by
      which these handbooks contrast with many compact neurological textbooks that were
      available at the time. For historiographical purposes, the three neurological
      handbooks considered here were important sources for the general study of the
      history of medicine and science and the history of neurology in particular.
      Moreover, they served as important catalyzers of the emergence of neurology as a
      new clinical specialty during the first decades of the twentieth century. 

PMID- 24083681
TI  - Chromosomal radiosensitivity analyzed by FISH in lymphocytes of prostate cancer
      patients and healthy donors.
AB  - It is known that about 5-10% of cancer patients show severe clinical side effects
      during and after radiotherapy due to enhanced sensitivity to ionizing radiation.
      Identification of those radiosensitive individuals by a reliable in vitro assay
      before onset of treatment would have a great impact on successful radiotherapy.
      We compared the radiosensitivity of the chromosomes 2, 11 and 17 in prostate
      cancer patients with and without severe side effects after radiotherapy and in
      age-matched healthy donors. Each cohort consisted of at least 10 donors.
      Peripheral blood lymphocytes were irradiated ex vivo with 0.5, 1 und 2 Gy
      ((137)Cs gamma rays). We investigated the radiosensitivity of the chromosomes 2,
      11 and 17 by scoring of 100 FISH painted metaphases for each dose point and donor
      group. Statistical analyses were performed by nonparametric tests as Mann-Whitney
      test and Kruskal-Wallis ANOVA, paired Wilcoxon rank test, chi(2) goodness-of-fit
      test and Spearman rank-order correlation at a significance level of P < 0.05.
      Analysis of the overall aberration yield revealed no significant differences
      between any donor groups. The translocation frequencies of the chromosomes 2, 11
      and 17 coincided with their relative size. Thus, none of the chromosomes analyzed
      were more or less radiosensitive with respect to the genomic translocation
      frequency. Additionally, neither of the chromosomes showed enhanced or diminished
      radiosensitivity in one of the donor groups. Furthermore, variance analyses
      revealed that the distribution pattern of the aberrations per donor did not
      differ in each donor group even after exposure to 2 Gy. Prostate cancer patients
      with and without side effects cannot be distinguished from healthy donors based
      on aberration yield after irradiation with gamma rays. 

PMID- 24083678
TI  - Sulindac activates NF-kappaB signaling in colon cancer cells.
AB  - BACKGROUND: The non-steroidal anti-inflammatory drug (NSAID) sulindac has shown
      efficacy in preventing colorectal cancer. This potent anti-tumorigenic effect is
      mediated through multiple cellular pathways but is also accompanied by
      gastrointestinal side effects, such as colon inflammation. We have recently shown
      that sulindac can cause up-regulation of pro-inflammatory factors in the mouse
      colon mucosa. The aim of this study was to determine the signaling pathways that
      mediate the transcriptional activation of pro-inflammatory cytokines in colon
      cancer epithelial cells treated with sulindac sulfide. RESULTS: We found that
      sulindac sulfide increased NF-kappaB signaling in HCT-15, HCT116, SW480 and SW620
      cells, although the level of induction varied between cell lines. The drug caused
      a decrease in IkappaBalpha levels and an increase of p65(RelA) binding to the NF
      kappaB DNA response element. It induced expression of IL-8, ICAM1 and A20, which
      was inhibited by the NF-kappaB inhibitor PDTC. Sulindac sulfide also induced
      activation of the AP-1 transcription factor, which co-operated with NF-kappaB in
      up-regulating IL-8. Up-regulation of NF-kappaB genes was most prominent in
      conditions where only a subset of cells was undergoing apoptosis. In TNFalpha
      stimulated conditions the drug treatment inhibited phosphorylation on
      IkappaBalpha (Ser 32) which is consistent with previous studies and indicates
      that sulindac sulfide can inhibit TNFalpha-induced NF-kappaB activation. Sulindac
      induced upregulation of NF-kappaB target genes occurred early in the proximal
      colon of mice given a diet containing sulindac for one week. CONCLUSIONS: This
      study shows for the first time that sulindac sulfide can induce pro-inflammatory
      NF-kappaB and AP-1 signaling as well as apoptosis in the same experimental
      conditions. Therefore, these results provide insights into the effect of sulindac
      on pro-inflammatory signaling pathways, as well as contribute to a better
      understanding of the mechanism of sulindac-induced gastrointestinal side effects.

PMID- 24083682
TI  - Lipoprotein(a) is not related to markers of insulin resistance in pregnancy.
AB  - BACKGROUND: Dyslipidemia, a major risk factor for cardiovascular disease is a
      common finding in patients with type 2 diabetes and among women with gestational
      diabetes. Elevated levels of lipoprotein(a) [Lp(a)] are linked to increased risk
      of cardiovascular disease. However, its relationship with insulin resistance,
      type 2 diabetes and gestational diabetes is controversial and unproven. Here we
      aimed to clarify whether Lp(a) levels are associated with insulin sensitivity in
      pregnancy. METHODS: Sixty-four women with gestational diabetes and 165 with
      normal glucose tolerance were enrolled in the study. Fasting Lp(a) serum levels
      were measured in all women at 24-28 weeks of gestation. RESULTS: In pregnancy,
      there was no significant difference in serum Lp(a) concentrations between the two
      groups. Its level did not correlate with markers of insulin resistance (HOMA-IR),
      insulin sensitivity (HOMA-S%), pancreatic beta-cell function (HOMA-B%) and
      insulin sensitivity in dynamic conditions (OGIS). In addition, fasting glucose
      and insulin levels and those throughout an oral glucose tolerance test were
      independent of Lp(a) concentrations in our study group. CONCLUSIONS: Lp(a) levels
      in pregnant women do not differ with respect to the presence or absence of
      gestational diabetes. Although influenced by some components of the lipid
      profile, such as triglycerides and HDL-C, insulin resistance in pregnancy is not
      affected by Lp(a).

PMID- 24083683
TI  - TGF-beta1 is associated with the progression of intracranial deep white matter
      lesions: a pilot study with 5 years of magnetic resonance imaging follow-up.
AB  - OBJECTIVES: Elevated expression of transforming growth factor (TGF)-beta1 has
      been reported in hereditary cerebral small-vessel (HCSV) disease. The aim of this
      study was to clarify whether TGF-beta1 is a risk factor for intracranial deep
      white matter lesions (DWLs) and their progression in a general elderly
      population. METHODS: The subjects included 81 participants (Groups DWL, DWLP, and
      C) who had voluntarily undergone a health examination and brain magnetic
      resonance imaging (MRI) in 2003 and 2008 and 43 age-matched patients with
      previous symptomatic brain infarctions. Deep white matter lesions were graded
      from Grade 0 to 3 according to the Fazekas classification. Group DWL (23
      subjects) was defined as DWLs with no progression in the grade level, and Group
      DWLP (progression of DWL) (12 subjects) was defined as DWLs with an increase in
      one or more grade number and an apparent worsening of Grade 3. Forty-six age
      matched control subjects with consistent normal brain MRI were included in Group
      C. The associations between DWLs and various vascular risk factors, including
      peripheral blood TGF-beta1 levels, were examined. RESULTS: In addition to the
      classical risk factors, the highest TGF-beta1 levels were found in Group DWLP.
      The TGF-beta1 levels were significantly higher in Group DWLP than in Group DWL,
      and DWLP was significantly correlated with elevated TGF-beta1 levels (odds ratio
      [OR]  =  1.72). CONCLUSIONS: The present data suggest that TGF-beta1 may be
      important in the pathogenesis and progression of DWLs, and it is expected to be
      useful as a clinical indicator reflecting the presence of intracranial white
      matter lesions.

PMID- 24083685
TI  - Time-resolved analysis of biological reactions based on heterogeneous assays in
      liquid plugs of nanoliter volume.
AB  - In this article, we present a concept which uses liquid plugs as reaction volumes
      for heterogeneous assay reactions to facilitate time-resolved analysis of
      biomolecular reactions. For this purpose, the reaction is first compartmentalized
      to a train of many identical plugs. Therefore, we established a simple fluidic
      setup build from off-the-shelf available tubing and connectors. It permits
      reliable formation of plugs and successive dosing of further assay reagents to
      these compartments (plug volume <5% CV). The time course of the reaction is
      obtained by routing the plugs successively through a detector. Thereby, the
      arrival time of a given plug at the detector represents the reaction time of the
      overall reaction at that moment. Thus, each analyzed plug represents a discrete
      state of the overall reaction. With this approach, we can achieve a temporal
      resolution as small as one second, which hardly can be met by conventional
      analytical methods for analysis of endogenous biological compounds. For analysis
      of the content of the plugs, we developed a method which allows for heterogeneous
      assays in two-phase flow. For this purpose, functionalized superparamagnetic
      beads are enclosed in the plugs for specific binding of the assay product.
      Purification from supernatant species is achieved by transferring the beads with
      bound analyte across the phase boundary between aqueous plugs and water
      immiscible carrier fluid. We demonstrate this assay principle exemplarily for a
      sandwich immunoassay (cytokine IL-8). Time-resolved analysis is validated by
      monitoring a cell-free in vitro expression reaction (turboGFP) in plugs and
      conventionally in bulk solution. We show that our approach allows for analyzing
      the entire course of a reaction in a single run. It permits kinetic studies of
      biological processes with significantly reduced experimental effort and
      consumption of costly reagents. 

PMID- 24083684
TI  - Human endometrial mesenchymal stem cells modulate the tissue response and
      mechanical behavior of polyamide mesh implants for pelvic organ prolapse repair.
AB  - BACKGROUND: Pelvic organ prolapse (POP) is defined as the descent of one or more
      of the pelvic structures into the vagina and includes uterine, vaginal vault, and
      anterior or posterior vaginal wall prolapse. The treatment of POP may include
      implantation of a synthetic mesh. However, the long-term benefit of mesh surgery
      is controversial due to complications such as mesh exposure or pain. The aim of
      this study was to use a tissue engineering (TE) approach to assess the in vivo
      biological and biomechanical behavior of a new gelatin/polyamide mesh, seeded
      with a novel source of mesenchymal stem cells in a subcutaneous rat model of
      wound repair. METHODS: W5C5-enriched human endometrial mesenchymal stem cells
      (eMSC) were seeded onto meshes (gelatin-coated polyamide knit) at 100,000
      cells/cm2. Meshes, with or without cells were subcutaneously implanted dorsally
      in immunocompromised rats for 7, 30, 60, and 90 days. Flow cytometry was used to
      detect DiO labeled cells after explantation. Immunohistochemical assessment of
      foreign body reaction and tissue integration were conducted. Total collagen and
      the levels of collagens type III and type I were determined. Uniaxial tensiometry
      was performed on explanted meshes, originally seeded with and without cells, at
      days 7 and 90. RESULTS: Implanted meshes were well tolerated, with labeled cells
      detected on the mesh up to 14 days postimplantation. Meshes with cells promoted
      significantly more neovascularization at 7 days (p<0.05) and attracted fewer
      macrophages at 90 days (p<0.05). Similarly, leukocyte infiltration was
      significantly lower in the cell-seeded meshes at 90 days (p<0.05). Meshes with
      cells were generally less stiff than those without cells, after 7 and 90 days
      implantation. CONCLUSION: The TE approach used in this study significantly
      reduced the number of inflammatory cells around the implanted mesh and promoted
      neovascularization. Seeding with eMSC exerts an anti-inflammatory effect and
      promotes wound repair with new tissue growth and minimal fibrosis, and produces
      mesh with greater extensibility. Cell seeding onto polyamide/gelatin mesh
      improves mesh biocompatibility and may be an alternative option for future
      treatment of POP.

PMID- 24083686
TI  - Cost-effectiveness of osteo-odonto keratoprosthesis in Singapore.
AB  - PURPOSE: To determine the long-term cost-effectiveness of osteo-odonto
      keratoprosthesis (OOKP) relative to no treatment among patients with end-stage
      corneal and ocular surface diseases in Singapore. DESIGN: Cost-effectiveness
      analysis based on data from a retrospective cohort study. METHODS: From a health
      system perspective, we calculated the incremental cost-effectiveness ratio of
      OOKP treatment relative to no treatment over a 30-year horizon, based on data
      from a cohort of 23 patients who underwent OOKP surgery between 2004 and 2009 at
      Singapore National Eye Centre. Preoperative and postoperative vision-related
      quality-of-life values were estimated from patients' visual outcomes and were
      used to calculate the gain in quality-adjusted life years (QALYs) resulting from
      OOKP treatment. Unsubsidized costs for surgery, consultations, examinations,
      medications, follow-up visits, and treatments for complications were retrieved
      from patients' bills to estimate the total costs associated with OOKP treatment.
      Sensitivity analyses were conducted to test the robustness of the model. RESULTS:
      Over a 30-year period, OOKP treatment, compared with no treatment, improved QALYs
      by 3.991 among patients with end-stage corneal and ocular surface diseases at an
      additional cost of S$67 840 (US$55 150), resulting in an incremental cost
      effectiveness ratio of S$17 000/QALY (US$13 820/QALY). CONCLUSIONS: Based on
      commonly cited cost-effectiveness benchmarks, the OOKP is a cost-effective
      treatment for patients with end-stage corneal and ocular surface diseases.

PMID- 24083688
TI  - Effectiveness of cervical cancer screening based on a mathematical screening
      model using data from the Hiroshima Prefecture Cancer Registry.
AB  - Here we assessed the effectiveness of cervical cancer screening using data from
      the Hiroshima Prefecture Cancer Registry regarding patient age at the start of
      screening and differences in screening intervals. A screening model was created
      to calculate the health status in relation to prognosis following cervical cancer
      screening and its influence on life expectancy. Epidemiological data on the
      mortality rate of cervical cancer by age groups and mortality rates from the
      Hiroshima Prefecture Cancer Registry were used for the model projections. Our
      results showed that life expectancy when screening rate was 100% compared with 0%
      was extended by approximately 1 month. Furthermore, when the incidence of
      cervical cancer was 0% compared with the screening rate was 100%, life expectancy
      was extended by a maximum of 3 months. Moreover, among individuals affected by
      cervical cancer, a difference of 13 years in life expectancy was calculated
      between screened and unscreened groups. 

PMID- 24083689
TI  - Overview of cancer registration research in the Asian Pacific from 2008-2013.
AB  - Cancer registration provides a firm basis for cancer control efforts and research
      into changing patterns of incidence, mortality, survival and prevalence is of
      obvious importance. Most of the countries of Asia have already published relevant
      data although the level of coverage and accuracy do vary a great deal both
      between and within countries. The present review concerns the relevant literature
      for the period 2008-2013, focusing on the types of research conducted and the
      conclusions that can be drawn with regard to what should be done in the future to
      translate the information available into effective intervention efforts to reduce
      the burden of disease. A major emphasis has been on determining variation in
      incidence and mortality/survival on the basis of ethnicity and socioeconomic as
      well as geographical background, as well as trends over time, either for cancer
      in general or specific organ sites. In addition a small number of papers focused
      on methodological, quality and cancer control issues, very pertinent to the
      future development of cancer registry based research. 

PMID- 24083687
TI  - Relationship between systemic cytokines and complement factor H Y402H
      polymorphism in patients with dry age-related macular degeneration.
AB  - PURPOSE: To investigate the relationship between systemic cytokines, the
      complement factor H (CFH) Y402H polymorphism, drusen load, and subfoveal
      choroidal thickness in patients with dry age-related macular degeneration (AMD).
      DESIGN: Cross-sectional study. METHODS: Forty-four dry AMD patients under care of
      the Retina Service at the University of British Columbia were enrolled. Drusen
      load was measured with an automated software algorithm in spectral-domain optical
      coherence tomography; subfoveal choroidal thickness was measured manually using
      enhanced depth imaging. Bio-Plex suspension assays (Bio-Rad Laboratories) were
      used to analyze cytokines in plasma and CFH Y402H was genotyped. Statistical
      analyses included analysis of covariance and Pearson correlation, corrected for
      multiple comparisons. RESULTS: The levels of 3 of 4 studied cytokines were
      significantly different among patients with CC, CT, or TT variants of the CFH
      Y402H polymorphism (P < .01). Patients with the at-risk CC variant had higher
      systemic levels of interleukin-6, interleukin-18, and tumor necrosis factor alpha
      than those with the CT variants, the TT variant, or both (P < .01). Interleukin
      1beta did not reach significance (P = .02), but did demonstrate a consistent
      trend. No correlation was found between plasma cytokines and drusen load or
      choroidal thickness (all P > .15). CONCLUSIONS: The elevated systemic levels of
      selected proinflammatory cytokines, including those representing products of
      inflammasome activation, were associated with the CC at-risk variant of the Y402H
      polymorphism and suggest that genetic factors regulate the inflammatory status in
      dry AMD patients. Our data support the central role of inflammation in the
      pathogenesis of AMD and provide further evidence of a systemic involvement in AMD
      etiology.

PMID- 24083690
TI  - Concomitant EGFR inhibitors combined with radiation for treatment of non-small
      cell lung carcinoma.
AB  - Epidermal growth factor receptor (EGFR) is considered to be one of the key driver
      genes in non-small cell lung cancer (NSCLC). Several clinical trials have shown
      great promise of EGFR tyrosine kinase inhibitors (TKIs) in the first-line
      treatment of NSCLC. Many advances have been made in the understanding of EGFR
      signal transduction network and the interaction between EGFR and tumor
      microenvironment in mediating cancer survival and development. The concomitant
      targeted therapy and radiation is a new strategy in the treatment of NSCLC. A
      number of preclinical studies have demonstrated synergistic anti-tumor activity
      in the combination of EGFR inhibitors and radiotherapy in vitro and in vivo. In
      the present review, we discuss the rationale of the combination of EGFR
      inhibitors and radiotherapy in the treatment of NSCLC. 

PMID- 24083691
TI  - Do the health claims made for Morinda citrifolia (Noni) harmonize with current
      scientific knowledge and evaluation of its biological effects.
AB  - Morinda citrifolia, also known as Great Morinda, Indian Mulberry, or Noni, is a
      plant belonging to the family Rubiaceae. A number of major chemical compounds
      have been identified in the leaves, roots, and fruits of Noni plant. The fruit
      juice is in high demand in alternative medicine for different kinds for illnesses
      such as arthritis, diabetes, high blood pressure, muscle ached and pains,
      menstrual difficulties, headache, heart diseases, AIDS, gastric ulcer, sprains,
      mental depression, senility, poor digestion, arteriosclerosis, blood vessel
      problems, and drug addiction. Several studies have also demonstrated the anti
      inflammatory, antioxidant and apoptosis-inducing effect of Noni in various
      cancers. Based on a toxicological assessment, Noni juice was considered as safe.
      Though a large number of in vitro, and, to a certain extent, in vivo studies
      demonstrated a range of potentially beneficial effects, clinical data are
      essentially lacking. To what extent the findings from experimental
      pharmacological studies are of potential clinical relevance is not clear at
      present and this question needs to be explored in detail before an
      recommendations can be made. 

PMID- 24083692
TI  - Significance of caveolin-1 regulators in pancreatic cancer.
AB  - Caveolin-1 is a scaffold protein on the cell membrane. As the main component of
      caveolae, caveolin-1 is involved in many biological processes that include
      substance uptake and transmembrane signaling. Many of these processes and thus
      caveolin-1 contribute to cell transformation, tumorigenesis, and metastasis. Of
      particular interest are the dual rolesof tumor suppressor and oncogene that
      caveolin-1 appear to play in different malignancies, including pancreatic cancer.
      Therefore, analyzing caveolin-1 regulators and understanding their mechanisms of
      actionis key to identifying novel diagnostic and therapeutic tools for pancreatic
      cancer. This review details the mechanisms of action of caveolin-1 regulators and
      the potential significance for pancreatic cancer treatment. 

PMID- 24083693
TI  - Hepatitis B virus gene mutations and hepatocarcinogenesis.
AB  - Chronic hepatitis B virus (HBV) infection has long been the most common cause of
      hepatocellular carcinoma (HCC). However, some aspects of the pathogenesis of HBV
      infection and genesis of hepatitis B virus (HBV)-related hepatocellular carcinoma
      (HCC) are still inconclusive. An increasing number of published studies indicate
      that hepatitis B virus mutations are associated with risk of HCC. These
      variations include, in particular, mutations in ORF S,C,X gene regions. This mini
      review summarizes results of clinical studies and molecular mechanisms on the
      possible relations of HBV mutations with the development of hepatocellular
      carcinoma. 

PMID- 24083694
TI  - Personality traits in cancer patients.
AB  - BACKGROUND: This study was planned to investigate the personality traits of
      cancer patients in different treatment settings, and to correlate the
      demographics with the personality features. MATERIALS AND METHODS: A total of 237
      patients referred either to Marmara University School of Medicine (MUSM) Oncology
      Outpatient Unit or to the private office of the faculty between March 10th and
      April 22nd, 2010 were enrolled in the study. The Big Five Mini Test was used to
      evaluate the 40 personality traits of the patients. RESULTS: The study group
      consisted of 98 males (41.35%) and 139 females (58.65%) with a mean age of 51.
      Out of the 237, 73.9% had an educational level beyond the junior high school, and
      47.3% of all patients reported a positive family history for cancer. A
      significant difference in terms of reconcilability, extraversion, and
      responsibility was observed between patients admitting to the university
      outpatient clinic and the private office (p<0.05). Reconcilability and
      extraversion were found to differ between genders significantly (p<0.05). The
      description of the patients by him/herself or by relatives displayed a
      significant difference in terms of openness (p<0.05). Parameters such as
      educational level, family history of cancer, age and marital status showed no
      relevance to their characters. No discordance was observed between the self
      analysis of the patient and the patient's relatives. CONCLUSIONS: Patients with
      cancer are typically highly reconcilable and responsible, moderately stable, open
      and extraverted.

PMID- 24083695
TI  - Arab women's breast cancer screening practices: a literature review.
AB  - Breast cancer incidence and mortality rates are increasing in the Arab world and
      the involved women are often diagnosed at advanced stages of breast cancer. This
      literature review explores factors influencing Arab women's breast cancer
      screening behavior. Searched databases were: Medline, PubMed, Cochrane Database
      of Systematic Reviews, CINAHL Plus, Google Scholar, Index Medicus for WHO Eastern
      Mediterranean, and Asian Pacific Journal of Cancer Prevention. Breast cancer
      screening participation rates are low. Screening programs are opportunistic and
      relatively new to the region. Knowledge amongst women and health care providers,
      professional recommendation, socio-demographic factors, cultural traditions,
      beliefs, religious, social support, accessibility and perceived effectiveness of
      screening influence screening behavior. 

PMID- 24083696
TI  - Acute normovolemic hemodilution effects on perioperative coagulation in elderly
      patients undergoing hepatic carcinectomy.
AB  - BACKGROUND: Acute normovolemic hemodilution (ANH) has been widely used to prevent
      the massive blood loss during hepatic carcinoma. The influences of ANH on
      coagulation function are still controversy, especially in elderly patients. The
      study observed ANH effects on coagulation function and fibrinolysis in elderly
      patients undergoing the disease. MATERIALS AND METHODS: Thirty elderly patients
      (aged 60-70 yr) with liver cancer (ASA I or II) taken hepatic carcinectomy from
      February 2007 to February 2008 were randomly divided into ANH group (n=15) and
      control group (n=15). After tracheal intubation, patients in ANH group and
      control group were infused with 6% hydroxyethyl starch (130/0.4) and Ringer's
      solution, respectively. Blood samples were drawn from patients in both groups at
      five different time points: before anesthesia induction (T1), 30 min after ANH
      (T2), 1 h after start of operation (T3), immediately after operation (T4), and 24
      h after operation (T5). Then coagulation function, soluble fibrin monomer complex
      (SFMC), prothrombin fragment (F1+2), and platelet membrane glycoprotein (CD62P
      and activated GP IIb/GP IIIa) were measured. RESULTS: The perioperative blood
      loss and allogeneic blood transfusion were recorded during the surgery. The
      perioperative blood loss was not significantly different between two groups
      (p>0.05), but the volume of allogeneic blood transfusion in ANH group was
      significantly less than in control group (350.0+/-70.7) mL vs. (457.0+/-181.3) mL
      (p<0.01). Compared with the data of T1, the prothrombin time (PT) and activated
      partial thromboplastin time (APTT) measured after T3 were significantly longer
      (p<0.05) in both groups, but within normal range. There were no significant
      changes of thrombin time (TT) and D-dimer between two groups at different time
      points (p>0.05). SFMC and F1+2 increased in both groups, but were not
      statistically significant. PAC-1-positive cells and CD62P expressions in patients
      of ANH group were significantly lower than those at T1 (p<0.05) and T2-T5
      (p>0.05). CONCLUSIONS: ANH has no obvious impact on fibrinolysis and coagulation
      function in elderly patients undergoing resection of liver cancer. The study
      suggested that ANH is safe to use in elderly patients and it could reduce
      allogeneic blood transfusion.

PMID- 24083697
TI  - Screening for MiRNAs related to laryngeal squamous carcinoma stem cell radiation.
AB  - OBJECTIVE: To use microarray chip technology for screening of stem cell radiation
      related miRNAs in laryngeal squamous cell carcinoma; study and explore the
      relationship of miRNAs with radiosensitivity of laryngeal squamous cells. METHOD:
      After conventional culture and amplification of the laryngeal squamous carcinoma
      cell line Hep-2, CD 133+ cells were screened out with combination of isolated
      culture of stem cell microspheres and FACS for preparation of laryngeal cancer
      stem cells. After radiation treatment, miRNAs of laryngeal squamous carcinoma
      stem cells before and after radiation were enriched and purified. After
      microarray hybridization with mammalian miRNA and scanning of fluorescence
      signal, the miRNAs of laryngeal squamous carcinoma stem cells before and after
      radiation was subject to differential screening and clustering analysis. Real
      time quantitative RT-PCR was used to verify part of the differentially expressed
      miRNAs. RESULTS: 70 miRNAs related to laryngeal cancer stem cell radiation with 2
      fold difference in expression were screened out, in which 62 were down-regulated
      and 8 were up-regulated. Fluorescent quantitative RT-PCR results were consistent
      with miRNAs chip results. CONCLUSION: Some miRNAs may be involved in self
      regulation with laryngeal squamous carcinoma stem cell radiation.

PMID- 24083698
TI  - Cyclooxygenase-2 expression in urinary bladder transitional cell carcinoma and
      its association with clinicopathological characteristics.
AB  - BACKGROUND: Transitional cell carcinoma (TCC) is the most predominant type of
      urinary bladder tumor. As cyclooxygenase (COX)-2 is recently introduced as an
      attractive target molecule in bladder TCC, we evaluated the immunohistochemical
      expression of this marker and its association with several clinicopathological
      characteristics. MATERIALS AND METHODS: This cross-sectional study was performed
      in the Pathology department of Sina Hospital in Tehran, Iran during 2006-2011.
      Ninety-two paraffin embedded blocks were selected from patients with urinary
      bladder TCC who underwent cystectomy or transurethral resection (TUR). Then, we
      assessed COX-2 expression by immunohistochemical staining using antibody against
      COX-2. Staining in more than 5% of tumor cells was considered as positive
      expression. RESULTS: COX-2 was expressed in 50 % of our patients. This marker was
      markedly expressed in high grade bladder TCC (62.1%) versus other grades and
      there was statistically a significant difference in COX-2 expression between
      various grades (p=0.008). In addition, patients' age, lymphatic and perineurial
      invasion were associated with the expression of COX-2 (p=0.001, 0.015 and 0.039,
      respectively). However, other parameters such as stage, tumor size, venous
      invasion and lymph node metastasis did not show any significant relationship with
      this marker (all, p>0.05). CONCLUSIONS: COX-2 was expressed in urinary bladder
      TCC especially in high grade forms, advocating its probable role in the
      differentiation of this tumor. Accordingly, COX-2 could be a valuable biological
      target molecule in the evaluation and treatment of patients with bladder TCC.

PMID- 24083699
TI  - Pattern of tissue expression of CA-125 and HE4 in primary epithelial ovarian
      tumours and correlation with serum CA-125 levels.
AB  - The objective of this study is to assess tissue expression of CA-125 and HE4
      protein in primary benign and malignant epithelial tumours of the ovary and
      correlate with serum CA-125 levels. A total of 100 formalin-fixed, paraffin
      embedded sections of ovarian tumours which included serous adenoma (11), mucinous
      adenoma (42), serous carcinoma (20), mucinous carcinoma (12) and endometrioid
      carcinoma (15), histologically diagnosed between 1st January 2004 to 31st
      December 2012 at the University Malaya Medical Centre, were stained for HE4
      (rabbit polyclonal antibody, Abcam, UK) and CA-125 (mouse monoclonal antibody
      clone: OC125, Cell Marque Corporation, Rocklin, California, USA). Pre-operative
      serum CA-125 levels were obtained from the laboratory information system.
      Immunoscore (I score) for HE4 and CA-125 was given based on the intensity of
      staining and percentage of positive tumour cells and considered significant when
      it was >50 (intensity of staining multiplied by percentage of positive tumour
      cells). Serum CA-125 levels were compared with the I score of HE4 and CA-125 in
      tissues. We noted that the CA-125 levels in serum and tissues were significantly
      raised in malignant compared to benign ovarian tumours (p value<0.05). Tissue
      expression of HE4 protein was also significantly raised in malignant tumours
      compared to benign tumours (p value<0.05). We conclude that HE4 can be a useful
      tissue immunomarker in addition to CA-125. 

PMID- 24083700
TI  - Lymphangiogenic and angiogenic microvessel density in chinese patients with
      gastric carcinoma: correlation with clinicopathologic parameters and prognosis.
AB  - The incidence of gastric cancer worldwide, and in particular in developing
      countries, has shown a marked increase. Poor prognosis of gastric cancer patients
      occurs due to the rapid metastasis of the disease via the lymphatic and blood
      vessels. The aim of this study was to investigate the expression and the clinical
      significance of D2-40 and CD34 in human gastric cancer. D2-40 and CD34 expression
      wasdetected in 1,072 cases of Chinese patients with gastric carcinoma using
      immunohistochemistry. The lymphatic vessel density (LVD) and microvessel density
      (MVD) were calculated and analyzed and the correlation with the
      clinicopathological factors and prognosis was determined. The LVD and MVD of the
      gastric cancer cases were significantly higher compared to those of normal
      tissues (P < 0.05). The expression of D2-40-LVD and CD34-MVD in the malignancies
      were positively related to the age, tumor size, invasion depth, lymphatic
      metastasis and pathological tumor-node-metastasis (pTNM) (P < 0.05); However, no
      statistically significant difference was identified between them with the patient
      gender (P > 0.05). Up-regulation of D2-40 and CD34 expression was significantly
      correlated with the poor survival rate in univariate and multivariate analyses.
      The LVD marked by D2-40 and the MVD marked by CD34 were positively correlated to
      the clinicopathological factors of the malignancies and may play important role
      in the development and progression of gastric cancer. 

PMID- 24083701
TI  - Screening of differentially expressed genes related to bladder cancer and
      functional analysis with DNA microarray.
AB  - OBJECTIVE: The purpose of this study was to identify genes related to bladder
      cancer with samples from normal and disease cases by microarray chip. METHODS:
      After downloading the gene expression profile GSE3167 from Gene Expression
      Omnibus database which includes 50 bladder samples, comprising 9 normal and 41
      disease samples, differentially expressed genes were identified with packages in
      R language. The selected differentially expressed genes were further analyzed
      using bioinformatics methods. Firstly, molecular functions, biological processes
      and cell component analysis were researched by software Gestalt. Then, software
      String was used to search interaction relationships among differentially
      expressed genes, and hub genes of the network were selected. Finally, by using
      plugins of software Cytoscape, Mcode and Bingo, module analysis of hub-genes was
      performed. RESULTS: A total of 221 genes were identified as differentially
      expressed by comparing normal and disease bladder samples, and a network as well
      as the hub gene C1QBP was obtained from the network. The C1QBP module had the
      closest relationship to production of molecular mediators involved in
      inflammatory responses. CONCLUSION: We obtained differentially expressed genes of
      bladder cancer by microarray, and both PRDX2 and YWHAZ in the module with hub
      gene C1QBP were most significantly related to production of molecular mediators
      involved in inflammatory responses. From knowledge of inflammatory responses and
      cancer, our results showed that, the hub gene and its module could induce
      inflammation in bladder cancer. These related genes are candidate bio-markers for
      bladder cancer diagnosis and might be helpful in designing novel therapies.

PMID- 24083702
TI  - Allele and genotype frequencies of the polymorphic methylenetetrahydrofolate
      reductase and colorectal cancer among Jordanian population.
AB  - BACKGROUND: Methylenetetrahydrofolate reductase (MTHFR) is involved in DNA
      synthesis and repair. We here aimed to investigate two common polymorphisms,
      C677T and A1298C, with genotype and haplotype frequencies in colorectal cancer
      (CRC) cases among Jordanian. MATERIALS AND METHODS: 131 CRC cases were studied
      for MTHFR C677T and A1298C polymorphisms, compared to 117 controls taken from the
      general population, employing the PCR-RFLP technique. RESULTS: We found the
      frequency of the three different genotypes of MTHFR C677T among Jordanians to be
      CC: 61.7%, CT: 35.2%, and TT 3.1% among CRC cases and 50.9%, 38.8% and 10.3%
      among controls. Carriers of the TT genotype were less likely to have CRC
      (OR=0.25; 95%CI: 0.076-0.811; p=0.021) as compared to those with the CC genotype.
      Genotype analysis of MTHFR A12987C revealed AA: 38.9%, AC: 45%, and CC 16% among
      CRC cases and 37.4%, 50.4% and 12.2% among controls. There was no significant
      association between genetic polymorphism at this site and CRC. Haplotype analysis
      of MTHFR polymorphism at the two loci showed differential distribution of the TA
      haplotype (677T-1298A) between cases and controls. The TA haplotype was
      associated with a decreased risk for colorectal cancer (OR=0.6; 95% CI: 0.4-0.9,
      p=0.03). CONCLUSIONS: The genetic polymorphism of MTHFR at 677 and the TA
      haplotype may modulate the risk for CRC development among the Jordanian
      population. Our findings may reflect an importance of genes involved in folate
      metabolism in cancer risk.

PMID- 24083704
TI  - Depression and predictors in Taiwanese survivors with oral cancer.
AB  - BACKGROUND: Depression is a comorbid disabling problem and potentially affects
      patient likelihood of survival. The aims of this study were to recognize the
      characteristics of depression and investigate associated predictor factors in
      patients with oral cancers. METHODS: A cross-sectional and correlational design
      was used to collect data for this study conducted in northern Taiwan. A set of
      questionnaires was used to measure depression, symptom distress, performance
      status, social support, and demographic and disease-related information. Logistic
      regression was conducted to determine important factors predicting depression.
      RESULTS: A total of 132 oral cancer patients participated in this study. Of
      these, 18.2% were identified as depression cases. The patient average performance
      status score was 90 or higher. Patients reported mild-to-moderate levels of
      symptom distress. The majority of social support was from families. Religious
      belief, alcohol use, symptom distress, and social support from family were found
      to be important factors predicting depression. Patients with religious belief
      with alcohol use reported greater symptom distress, and those with lower levels
      of social support from families were significantly more likely to develop
      depression. CONCLUSIONS: Clinicians should assess patient emotional status and
      manage symptoms in a timely manner to enhance coping abilities. Supportive care
      provides assurance during the acute survivor phase.

PMID- 24083703
TI  - Treatment outcome for nasopharyngeal carcinoma in University Malaya Medical
      Centre from 2004-2008.
AB  - BACKGROUND: Nasopharyngeal carcinoma (NPC) is the commonest radiocurable cancer
      in Malaysia. This study aimed to determine the treatment outcomes and late
      effects of radiotherapy for NPC patients treated in University Malaya Medical
      Centre (UMMC). MATERIALS AND METHODS: All newly diagnosed patients with NPC
      referred for treatment to the Oncology unit at UMMC from 2004-2008 were
      retrospectively analyzed. Treatment outcomes were 5 years overall survival (OS),
      disease free survival (DFS), cause-specific survival (CSS), loco- regional
      control (LRC) and radiotherapy-related late effects. The Kaplan-Meier method was
      used for survival analysis and differences in survival according to AJCC stage
      was compared using the log-rank test. RESULTS: A total of 176 patients with newly
      diagnosed NPC were treated in UMMC during this period. Late presentation was
      common, with 33.5% presenting with T3-4 disease, 84.7% with N1-3 disease and
      75.6% with AJCC stage 3-4 disease. Radical RT was given to 162 patients with
      22.7% having RT alone and 69.3% having CCRT. The stipulated OTT was 7 weeks and
      72.2% managed to complete their RT within this time period. Neoadjuvant
      chemotherapy was given to 14.8% while adjuvant chemotherapy was administered to
      16.5%. The 5 years OS was 51.6% with a median follow up of 58 months. The 5 years
      OS according to stage were 81.8% for stage I, 77.9% for stage II, 47.4% for stage
      III and 25.9% for stage IV. The 5 years overall CSS, DFS and LRC were 54.4%,
      48.4% and 70.6%, respectively. RT related late effects were documented in 80.2%.
      The commonest was xerostomia (66.7%). Other documented late effects were hearing
      deficit (17.3%), visual deficit (3.1%), neck stiffness (3.1%) , dysphagia (3.4%),
      cranial nerve palsy (2.5%), pneumonitis (0.6%) and hypothyroidism (1.2%).
      CONCLUSIONS: The 5 years OS and LRC in this study are low compared to the latest
      studies especially those utilizing IMRT. Implementation of IMRT for NPC treatment
      should be strongly encouraged.

PMID- 24083705
TI  - Practice of skin cancer prevention among road traffic police officers in
      Malaysia.
AB  - BACKGROUND: The objective of this study was to determine the practice of skin
      cancer prevention among Malaysian road traffic police officers. MATERIALS AND
      METHODS: This cross-sectional study involved 202 Malaysian Road Police Traffic
      officers. Inclusion criteria were those officers who work wearing white uniform
      regulating traffic. The survey took place at the Police Traffic Station, Jln Tun
      H.S. Lee, Kuala Lumpur, the main Head Quarters of Malaysian's Traffic Department
      where almost 600 police traffic officers are employed. The police traffic
      officers are given the task to take care of the traffic from the main office of
      the police station, then, according to the task, the officers drive to their
      given location for their duty. Each task is approved by the Chief Traffic
      Inspector of Kuala Lumpur. Data collected in this study were analyzed using SPSS
      13, with the T-test for univariate analysis and multiple linear regression for
      multivariate analysis. RESULTS: A total of 202 road traffic police officers
      participated. The majority were older than 30 years of age, male, Malay, married,
      with secondary education, with monthly income more than 2000 Ringgit Malaysia
      (66.3%, 91.1%, 86.6%, 84.7%, 96%, 66.3%; respectively). Regarding the practice of
      skin cancer prevention, 84.6% of the study participants were found to wear hats,
      68.9% sunglasses and 85.6% clothing that covering most of the body but only 16.9%
      used a sunscreen when they were outdoors. When analysis of the factors that
      influenced the practice of skin cancer prevention was performed, univariate
      analysis revealed that gender, age and monthly income significantly influenced
      the practice of skin cancer prevention. For multivariate analysis, gender,
      monthly income and race significantly influenced the practice of using sunscreen
      among road traffic police officers (p<0.001, p=0.019, p=0.027; respectively).
      CONCLUSIONS: The practice of skin cancer prevention among the traffic police
      officers showed good practices in terms of wearinga hat, sun glasses and clothing
      that covers most of the body. However, the study revealed a poor practice of the
      use of sunscreen. The factors that influence the practice of sunscreen use were
      found to be gender, income, and race. The study suggests that more awareness
      campaign among traffic police officers is needed. Providing sunscreen for free
      for police traffic officers should be considered by the Police authorities.

PMID- 24083706
TI  - Clinical efficacy and prognosis factors for advanced hepatoblastoma in children:
      a 6-year retrospective study.
AB  - OBJECTIVE: This study aimed to investigate the effect of multimodality treatment
      of advanced paediatric hepatoblastoma (HB) and the factors affecting prognosis.
      METHODS: A total of 35 children underwent multimodality treatments consisting of
      chemotherapy, surgery, interventional therapy, and autologous peripheral blood
      stem cell transplantation. The patients were followed up every month. RESULTS:
      Serum AFP levels in 33 out of 35 patients in this study were significantly
      increased (P = 0.0002). According to the statistical scatter plot, the values of
      serum AFP on the 25th, 50th, and 75th percentages were 1,210, 1,210 and 28,318
      ng/dl, respectively. Of the 35 cases, 21 were stage IV. 18 cases were treated
      with systemic chemotherapy before surgery, and 3 cases with locally
      interventional chemotherapy before surgery. Statistical analysis showed that the
      preferred interventional treatment affected prognosis, and that there was a
      statistically significant difference (P = 0.024). Some 33 patients completed the
      follow-up, of which 17 were in complete remission (CR), 5 were in partial
      remission (PR), 1 became disease progressive (DP) , and 10 died. The remission
      and overall survival rates were 66.7% (22/33) and 69.7% (23/33), respectively.
      Patients with the mixed HB phenotypes had worse prognoses than the epithelial
      phenotype (P < 0.001), and patients in stage IV had a lower survival rate than
      those in stage III (P < 0.001). CONCLUSION: Multimodality treatment can
      effectively improve remission rate and prolong the survival of children with
      advanced HB. In addition, alpha-fetoprotein (AFP), a tumor marker of liver
      malignant tumors, HB pathological classification, and staging are highly useful
      in predicting prognosis.

PMID- 24083707
TI  - Survival rate of breast cancer patients in Malaysia: a population-based study.
AB  - Breast cancer is the most common cancer among Malaysian women. Other than
      hospital-based results, there are no documented population-based survival rates
      of Malaysian women for breast cancers. This population- based retrospective
      cohort study was therefore conducted. Data were obtained from Health Informatics
      Centre, Ministry of Health Malaysia, National Cancer Registry and National
      Registration Department for the period from 1st Jan 2000 to 31st December 2005.
      Cases were captured by ICD-10 and linked to death certificates to identify the
      status. Only complete data were analysed. Survival time was calculated from the
      estimated date of diagnosis to the date of death or date of loss to follow-up.
      Observed survival rates were estimated by Kaplan- Meier method using SPSS
      Statistical Software version 17. A total of 10,230 complete data sets were
      analysed. The mean age at diagnosis was 50.6 years old. The overall 5-year
      survival rate was 49% with median survival time of 68.1 months. Indian women had
      a higher survival rate of 54% compared to Chinese women (49%) and Malays (45%).
      The overall 5-year survival rate of breast cancer patient among Malaysian women
      was still low for the cohort of 2000 to 2005 as compared to survival rates in
      developed nations. Therefore, it is necessary to enhance the strategies for early
      detection and intervention. 

PMID- 24083708
TI  - Effect of variation of ABCB1 and ABCC3 genotypes on the survival of bone tumor
      cases after chemotherapy.
AB  - We conducted a comprehensive study to investigate the role of genes involved in
      transport pathways in response to chemotherapy and clinical outcome of
      osteosarcoma cases. Genotyping of six SNPs was performed in a 384-well plate
      format on the Sequenom MassARRAY platform for 208 osteosarcoma patients to reveal
      any correlations of the six SNPs with response to chemotherapy and clinical
      outcome. Individuals with the ABCB1 rs1128503 TT and ABCC3 rs4148416 TT genotypes
      had a higher probability of responding poorly to chemotherapy, indicated by odds
      ratios (ORs) of 2.46 (95%CI, 1.21-5.74) and 3.78 (95% CI, 1.20-13.85),
      respectively. Moreover, the ABCB1 rs1128503 TT and ABCC3 rs4148416 TT genotypes
      were significantly associated with shorter disease- free survival (DFS) and
      overall survival (OS). Our study found the two SNPs in two transporter genes and
      one phase II metabolism enzyme to be associated with response to chemotherapy and
      overall survival in osteosarcoma patients, suggesting potential prognostic
      biomarker applications of the two SNPs. 

PMID- 24083709
TI  - Curcumin inhibits human non-small cell lung cancer A549 cell proliferation
      through regulation of Bcl-2/Bax and cytochrome C.
AB  - We intended to study the mechanism of the inhibitory action of curcumin on human
      non-small cell lung cancer A549 cell. The cell growth was determined by CCK-8
      assay, and the results indicated that curcumin inhibited the cell proliferation
      in a concentration dependent manner. And to further confirm the relative anti
      cancer mechanism of curcumin, RT-PCR was carried out to analysis the expression
      of relative apoptotic proteins Bax, Bcl-2. We found that curcumin could up
      regulate the expression of Bax but down-regulate the expression of Bcl-2 in A549
      cells. In addition, curcumin affect the mitochondrial apoptosis pathway. These
      results suggested that curcumin inhibited cancer cell growth through the
      regulation of Bcl-2/Bax and affect the mitochondrial apoptosis pathway. 

PMID- 24083710
TI  - Morinda citrifolia (Noni) alters oxidative stress marker and antioxidant activity
      in cervical cancer cell lines.
AB  - BACKGROUND: Cervical cancer, the second most common cancer in women, has a high
      mortality rate. Cisplatin, an antitumor agent, is generally used for its
      treatment. However, the administration of cisplatin is associated with side
      effects and intrinsic resistance. Morinda citrifolia (Noni), a natural plant
      product, has been shown to have antioxidant activities in vitro and in vivo.
      MATERIALS AND METHODS: Both HeLa and SiHa cervical cancer cell lines were treated
      with 10% Noni, 10 mg/dl cisplatin, or a combination of both 10% Noni and 10 mg/dl
      cisplatin for 24 hours. Post culturing, the cells were pelleted and stored at 
      70oC for malondialdehyde and catalase assays. RESULTS: On treatment with Noni,
      CP, and their combination, the level of MDA decreased by 0.76 fold, 0.49 fold,
      and 0.68 fold respectively in HeLa cells; and by 0.93 fold, 0.67 fold, and 0.79
      fold respectively in SiHa cells, as compared to their controls; whereas catalase
      activity increased by 1.61 fold, 0.54 fold, and 2.35 fold, respectively in HeLa
      cells; and by 0.98 fold, 0.39 fold, and 1.85 fold respectively in SiHa cells.
      CONCLUSIONS: A decrease in level of lipid peroxidation and an increase in
      catalase activity were observed with Noni by itself and the effect ameliorated
      changes observed with cisplatin when given in combination.

PMID- 24083711
TI  - Effects of gastric cancer cells on the differentiation of Treg cells.
AB  - The aim of this study was evaluated the prevalence of Treg cells in peripheral
      blood in patients with gastric cancer, and investigate the effect of gastric
      cancer cells on their differentiation. ELISA was employed to assess the
      concentrations of TGF-beta and IL-10 in gastric cancer patients' serum. Then,
      mouse gastric cancer cells were co-cultured with T lymphocytes or T lymphocytes +
      anti-TGF-beta. Flow cytometric analysis and RT-PCR were then performed to detect
      Treg cells and TGF-beta and IL-10 expression in gastric cancer cells. Our data
      showed that the expression of TGF-beta and IL-10 in the patients with gastric
      cancer was increased compared to the case with healthy donors. The population of
      Treg cells and the expression levels of TGF-beta and IL-10 in the co-culture
      group were much higher than in the control group (18.6% vs 9.5%) (P<0.05).
      Moreover, the population of Treg cells and the expression levels of TGF-beta and
      IL-10 in the co-culture systerm were clearly decreased after addition of anti-TGF
      beta (7.7% vs 19.6%) (P<0.01). In conclusion, gastric cancer cells may induce
      Treg cell differentiation through TGF-beta, and further promote
      immunosuppression. 

PMID- 24083712
TI  - Antioxidants may protect cancer cells from apoptosis signals and enhance cell
      viability.
AB  - Quercetin is one of the most abundant dietary flavonoids widely present in many
      fruits and vegetables. Previous in vitro studies has shown that quercetin acts as
      an antioxidant and anti-inflammatory agent and it has potent anticarcinogenic
      properties as an apoptosis inducer. In this study we examined apoptotic effects
      of quercetin on the K562 erythroleukemia cell line. K562 cells were induced to
      undergo apoptosis by hydrogen peroxide. Cell viability and apoptosis level were
      assessed by annexin V and PI staining methods using flow cytometry. Viability of
      K562 cells was increased by low dose of quercetin (5-100 MUM) for 3 hours. High
      doses of quercetin proved toxic (100-500 MUM, 24 hours) and resulted in decrease
      of K562 cell viability as expected (P<0.01). As to results, 100 MUM quercetin was
      defined as a protective dose. Also, K562 cell apoptosis due to hydrogen peroxide
      was decreased in a dose dependent manner. As indicated in previous studies,
      reduction of superoxides by free radical scavengers like quercetin could be
      beneficial for prevention of cancer but consumption of such flavonoids during
      cancer treatment may weaken effects of chemotherapeutics and radiotherapy.
      Especially cancer patients should be carefully considered for traditional
      phytotherapy during cancer treatment, which can lead to controversial results. 

PMID- 24083713
TI  - The synergistic anticancer effect of artesunate combined with allicin in
      osteosarcoma cell line in vitro and in vivo.
AB  - BACKGROUND: Artesunate, extracted from Artemisia annua, has been proven to have
      anti-cancer potential. Allicin, diallyl thiosulfinate, the main biologically
      active compound derived from garlic, is also of interest in cancer treatment
      research. This object of this report was to document synergistic effects of
      artesunate combined with allicin on osteosarcoma cell lines in vitro and in vivo.
      METHODS: After treatment with artesunate and allicin at various concentrations,
      the viability of osteosarcoma cells was analyzed by MTT method, with assessment
      of invasion and motility, colony formation and apoptosis. Western Blotting was
      performed to determine the expression of caspase-3/9, and activity was also
      detected after drug treatment. Moreover, in a nude mouse model established with
      orthotopic xenograft tumors, tumor weight and volume were monitored after drug
      administration via the intraperitoneal (i.p.) route. RESULTS: The viability of
      osteosarcoma cells in the combination group was significantly decreased in a
      concentration and time dependent manner; moreover, invasion, motility and colony
      formation ability were significantly suppressed and the apoptotic rate was
      significantly increased through caspase-3/9 expression and activity enhancement
      in the combination group. Furthermore, suppression of tumor growth was evident in
      vivo. CONCLUSION: Our results indicated that artesunate and allicin in
      combination exert synergistic effects on osteosarcoma cell proliferation and
      apoptosis.

PMID- 24083714
TI  - Mining proteins associated with oral squamous cell carcinoma in complex networks.
AB  - The purpose of this study was to construct a protein-protein interaction (PPI)
      network related to oral squamous cell carcinoma (OSCC). Each protein was ranked
      and those most associated with OSCC were mined within the network. First, OSCC
      related genes were retrieved from the Online Mendelian Inheritance in Man (OMIM)
      database. Then they were mapped to their protein identifiers and a seed set of
      proteins was built. The seed proteins were expanded using the nearest neighbor
      expansion method to construct a PPI network through the Online Predicated Human
      Interaction Database (OPHID). The network was verified to be statistically
      significant, the score of each protein was evaluated by algorithm, then the OSCC
      related proteins were ranked. 38 OSCC related seed proteins were expanded to 750
      protein pairs. A protein-protein interaction nerwork was then constructed and the
      30 top-ranked proteins listed. The four highest-scoring seed proteins were SMAD4,
      CTNNB1, HRAS, NOTCH1, and four non-seed proteins P53, EP300, SMAD3, SRC were
      mined using the nearest neighbor expansion method. The methods shown here may
      facilitate the discovery of important OSCC proteins and guide medical researchers
      in further pertinent studies. 

PMID- 24083715
TI  - Protective role of aspirin, vitamin C, and zinc and their effects on zinc status
      in the DMH-induced colon carcinoma model.
AB  - Chemoprotection refers to the use of specific natural or synthetic chemical
      agents to suppress or prevent the progression to cancer. The purpose of this
      study is to assess the protective effect of aspirin, vitamin C or zinc in a
      dimethyl hydrazine (DMH) colon carcinoma model in rats and to investigate the
      effect of these supplements on changes associated with colonic zinc status. Rats
      were randomly divided into three groups, group 1 (aspirin), group 2 (vitamin C)
      and group 3 (zinc), each being subdivided into two groups and given subcutaneous
      injection of DMH (30 mg/kg body wt) twice a week for 3 months and sacrificed at 4
      months (A-precancer model) and 6 months (B-cancer model). Groups 1, 2, 3 were
      simultaneously given aspirin, vitamin C, or zinc supplement respectively from the
      beginning till the end of the study. It was observed that 87.5% of rats co
      treated with aspirin or vitamin C showed normal colonic histology, along with a
      significant decrease in colonic tissue zinc at both time points. Rats co-treated
      with zinc showed 100% reduction in tumor incidence with no significant change in
      colonic tissue zinc. Plasma zinc, colonic CuZnSOD (copper-zinc superoxide
      dismutase) and alkaline phosphatase activity showed no significant changes in all
      3 cotreated groups. These results suggest that aspirin, vitamin C or zinc given
      separately, exert a chemoprotective effect against chemically induced DMH colonic
      preneoplastic progression and colonic carcinogenesis in rats. The inhibitory
      effects are associated with maintaining the colonic tissue zinc levels and zinc
      enzymes at near normal without significant changes. 

PMID- 24083716
TI  - Effects of vinorelbine on cisplatin resistance reversal in human lung cancer
      A549/DDP cells.
AB  - Multi-drug resistance (MDR) is an essential aspect of human lung cancer
      chemotherapy failure. Recent studies have shown that vinorelbine is involved in
      underlying processes in human tumors, reversing the MDR inseveral types of cancer
      cells. However, the roles and potential mechanism are not fully clear. In this
      study, we explored effects of vinorelbine in multi-drug resistance reversal of
      human lung cancer A549/DDP cells. We found that vinorelbine increased drug
      sensitivity to cisplatin and intracellular accumulation of rhodamine-123, while
      decreasing expression of P-glycoprotein (P-gp), multi-drug resistance-associated
      protein (MRP1) and glutathione-S-transferase Pi (GST-Pi) in A549/DDP cells. At
      the same time, we also established downregulation of p-Akt and decreased
      transcriptional activation of NF-kappaB and twist after vinorelbine treatment.
      The results indicated that vinorelbine might be used as a potential therapeutic
      strategy in human lung cancer. 

PMID- 24083717
TI  - Multidisciplinary collaborative therapy for 30 children with orbital
      rhabdomyosarcoma.
AB  - OBJECTIVE: To explore clinical experience and propose new ideas for treating
      children diagnosed with orbital rhabdomyosarcoma (RMS). METHODS: We
      retrospectively analyzed the clinical data for30 patients (16 males and 14
      females, with a median age of 6.2 years) with primary orbital RMS who were
      enrolled in the Department of Eye Oncology and Pediatrics of our hospital from
      November 2004 to December 2012. International Rhabdomyosarcoma Organization
      Staging Standards indicated that among the 30 patients, 4 cases were in phase II,
      20 were in phase III, and 6 were in phase IV. All patients underwent a
      multidisciplinary collaborative model of comprehensive treatment (surgery,
      chemotherapy, external radiotherapy, 125I radioactive particle implantation, and
      autologous peripheral blood stem-cell transplantation). RESULTS: Follow-up was
      conducted until March 2013, with a median follow-up time of 47.2 months (5 to 95
      months), and 7 deaths occurred. The 2-year estimated survival rate reached 86.1%,
      the >=3-year estimated survival rate was 77%, and the 5-year estimated survival
      rate was 70.6%. CONCLUSIONS: The multidisciplinary collaborative model can be a
      safe and effective approach to the comprehensive treatment of children with
      orbital RMS. It has clinical significance in improving the tumor remission rate.

PMID- 24083718
TI  - Evaluation of BreastLight as a tool for early detection of breast lesions among
      females attending National Cancer Institute, Cairo University.
AB  - BACKGROUND: Breast illumination was suggested as a simple method for breast
      cancer screening. BreastLight is a simple apparatus for this purpose. OBJECTIVE:
      To evaluate the diagnostic performance of BreastLight as a screening tool of
      breast cancer in comparison to mammography and histopathology. MATERIALS AND
      METHODS: This hospital-based cross sectional study was conducted in the
      mammography unit of the radiodiagnosis department at National Cancer Institute,
      Cairo University. All participants were subjected to breast examination with the
      BreastLight tool, mammography and ultrasonography. Suspicious cases were biopsied
      for histopathological examination which is considered as a gold standard.
      RESULTS: The mean age of the participants was 46.3+/-12.4 years. Breast
      illumination method had sensitivity, specificity, positive predictive value,
      negative predictive value and total accuracy of 93.0%, 73.7%, 91.4%, 77.8% and
      88.2%, respectively in detection of breast cancer. CONCLUSIONS: Breast
      illumination method with BreastLight apparatus is a promising easy-to-use tool to
      screen for breast cancer suitable for primary health care physician or at-home
      use. It needs further evaluation especially in asymptomatic women.

PMID- 24083719
TI  - Chloroquine and valproic acid combined treatment in vitro has enhanced
      cytotoxicity in an osteosarcoma cell line.
AB  - Choroquine (CQ) and valproic acid (VPA) have been extensively studied for
      biological effects. Here, we focused on efficacy of combined CQ and VPA on
      osteosarcoma cell lines. Viability of osteosarcoma cell lines (U20S and HOS) was
      analyzed by MTT assay. Apoptotic assays and colony formation assays were also
      applied. ROS generation and Western Blotting were performed to determine the
      mechanism of CQ and VPA combination in the process of apoptosis. The viability of
      different osteosarcoma cell lines significantly decreased after CQ and VPA
      combination treatment compared with either drug used alone, and apoptosis was
      increased significantly. ROS generation was triggered leading to expression of
      apoptosis related genes being increased and of anti- apoptotic related genes
      being decreased. From our data shown here, CQ and VPA combination treatment in
      vitro enhanced cytotoxicy to osteosarcoma cells. 

PMID- 24083720
TI  - Experiences of family of patient with newly diagnosed advanced terminal stage
      hepatocellular cancer.
AB  - BACKGROUND: Hepatocellular carcinoma (HCC) is the most common primary liver
      cancer and the third leading cause of cancer-related death worldwide due to its
      generally poor prognosis. Caregiver burden for liver cancer cases is higher than
      with other cancer and needs especial attention. METHODS: To explore the
      experiences of families of patients with newly diagnosed advanced terminal stage
      hepatocellular cancer by interview. RESULTS: Nine participants were recruited in
      this study. Content analysis of the interviews revealed four themes: blaming
      oneself, disrupting the pace of life, searching all possible regimens, and not
      letting go. CONCLUSIONS: This study provides new insight into the needs and
      support of family members especially when they are facing loved ones with newly
      diagnosed advanced terminal stage HCC. These results will inform future
      supportive care service development and intervention research aimed at providing
      assistance in reducing unmet supportive care needs and psychological distress of
      these family members.

PMID- 24083721
TI  - Survival analysis in advanced non small cell lung cancer treated with platinum
      based chemotherapy in combination with paclitaxel, gemcitabine and etoposide.
AB  - BACKGROUND: The wide spectrum of clinical features in advanced stages of non
      small cell lung cancer (NSCLC) probably contributes to disparities in outcomes
      because of different prognostic variables significant for stage IIIB/IV patients.
      Hence the aim of this study was to check for favorable response of patients to
      various chemotherapeutic combinations with respect to patient survival in stage
      IIIB and stage IV NSCLC disease. We selected those patients for our study who
      were receiving treatment with paclitaxel, gemcitabine or etoposide in combination
      with platinum based drugs. MATERIALS AND METHODS: Seventy-two patients who
      visited the hospital from June 2009 to November 2012 with confirmed diagnosis of
      lung cancer were included, and data were collected for follow up and classified
      according to treatment received with respect to patients' regimen and response,
      and overall survival. This study analyzed tumor variables that were associated
      with clinical outcome in advanced NSCLC patients who were undergoing first-line
      chemotherapy for stage IIIB/IV NSCLC. RESULTS: Comparative data on various
      parameters like age, gender, stage, histology, site of disease, metastatic site
      and chemo-regimens was analyzed; these parameters predicted variable significant
      improvement for overall survival (p>=0.05). One and two year survival rates were
      20.8% and 15.3% . CONCLUSIONS: In this study we found slight improvement in
      survival rates in NSCLC and clinical outcomes with one combination
      (carboplatin+paclitaxel). Overall there were only marginal differences in
      survival rates for other chemo-regimens evaluated in this study.

PMID- 24083722
TI  - Cigarette smoking and prostate cancer risk: negative results of the Seoul Male
      Cancer Cohort Study.
AB  - We evaluated cigarette smoking as a risk factor for prostate cancer in a
      prospective, population-based cohort study. The subjects were 14,450 males among
      the participants in the Seoul Male Cancer Cohort Study who had at least 1-year
      follow-up. They were followed up between 1993 and 2008. During the 16-year follow
      up period, 87 cases of prostate cancer occurred over the 207,326 person-years of
      the study. The age-adjusted relative risks of past and current smokers at entry
      were 0.60 (95%CI: 0.34-1.06) and 0.70 (95%CI: 0.43-1.13), respectively,
      suggesting that cigarette smoking may not be a risk factor for prostate cancer.
      The relationship between prostate cancer and other modifiable factors, such as
      Westernized diet, should be studied with the goal of establishing prevention
      programs for prostate cancer. 

PMID- 24083723
TI  - Variation of blood T lymphocyte subgroups in patients with non- small cell lung
      cancer.
AB  - OBJECTIVES: To study variation in T lymphocyte subgoups and its clinical
      significance in non-small cell lung cancer (NSCLC). METHODS: Levels of CD3+ ,
      CD4+ , CD8+ , CD4+/CD8+, NK and Treg cells in peripheral blood of NSCLC cases and
      healthy adults were determined by flow cytometry. RESULTS: CD3+ , CD4+ and
      CD4+/CD8+ ratio and NK cells in NSCLCs were decreased significantly in comparison
      with the control group (P < 0.01), and decreased with increase in the clinical
      stage of NSCLC, while CD8+ cells demonstrated no significant change (P > 0.05).
      Treg cells were significantly more frequent than in the control group (P < 0.01),
      and increased with the clinical stage of NSCLC. CONCLUSION: The cellular immune
      function of the NSCLC patients is lowered. It is important to detect change of T
      lymphocyte subgroups by flow cytometry for the diagnosis, treatment and
      prognostic assessment of NSCLC patients.

PMID- 24083724
TI  - Effect of miR27a on proliferation and invasion in colonic cancer cells.
AB  - The aim of this study was to detect the expression of miR196a, miR146a, miR27a
      and miR200a in patients with colon cancer, and investigate the effect of miR27a
      expression on proliferation and invasion in colonic cancer cells. RT-PCR was
      employed to detect the expression levels in colon cancers. Then, colon cancer
      cells were cultured and transfected with 100 nM of miR27a mimics (80 nmol/L) or
      80 nM miR27a inhibitors (80 nmol/L) in 24-well plates. Proliferation and invasion
      of colonic cancer cells were then determined by CCK-8 and Transwell assays,
      respectively. Our data showed miR27a to be high-expressed in patients with colon
      cancer. In addition, proliferation and invasion in the miR27a mimic group were
      significantly higher than in the control group and negative group (P<0.05),
      while, proliferation and invasion in the miR27a inhibitor group were obviously
      lowered (P<0.05). In conclusion, high expression of miR27a may play an important
      role in enhancing proliferation and invasion of colon cancer cells. 

PMID- 24083725
TI  - ERCC1 expression does not predict survival and treatment response in advanced
      stage non-small cell lung cancer cases treated with platinum based chemotherapy.
AB  - BACKGROUND: ERCC1 is considered as a promising molecular marker that may predict
      platinum based chemotherapy response in non small cell lung cancer patients. We
      therefore investigated whether its expression is indeed associated with clinical
      outcomes in advanced stage NSCLC patients. MATERIALS AND METHODS: Pretreatment
      tumor biopsy samples of 83 stage 3B and 4 non-small cell lung cancer patients
      treated with platinum based chemotherapy were retrospectively analyzed for
      immunohistochemical ERCC1 expression. None of the patients received curative
      surgery or radiotherapy. RESULTS: By calculating H- scores regarding the extent
      and intensity of immunohistochemical staining of tumor biopsy samples, ERCC1
      expression was found to be positive in 50 patients (60.2%). ERCC1 positive and
      negative groups had no statistically significant differences regarding treatment
      response, progression free survival and overall survival (respectively p=0.161;
      p=0.412; p=0.823). CONCLUSIONS: In our study we found no association between
      ERCC1 expression and survival or treatment response. The study has some
      limitations, such as small sample size and retrospective analysis method. There
      is need of more knowledge for use of ERCC1 guided chemotherapy regimens in
      advanced stage NSCLC.

PMID- 24083726
TI  - Autophagy inhibition sensitizes cisplatin cytotoxicity in human gastric cancer
      cell line SGC7901.
AB  - We aimed to investigate the mechanism and effects of autophagy on cisplatin (DDP)
      induced apoptosis in human gastric cancer cell line SGC7901. After SGC7901 cells
      were treated with DDP and/or chloroquine, cell proliferation was measured using
      MTT assay; cell apoptosis was determined by flow cytometry; autophagy and
      apotosis-related proteins expression were detected by Western blot; and
      quantitative analysis of autophagy after monodansylcadaverine (MDC) staining was
      performed using fluorescence microscopy. We found after treatment with 5 mg/L DDP
      for 24 h, the rates of cell apoptosis were (21.07+/-2.12)%. Autophagy,
      characterized by an increase in the number of autophagic vesicles and the level
      of LC3-II protein was observed in cells treated with DDP. After inhibition of
      autophagy by chloroquine, the rates of cell apoptosis were increased to (30.16+/
      3.54)%, and the level of Caspase-3 and P53 protein were increased, and Bcl-2
      protein was decreased. Therefore, autophagy protects human gastric cancer cell
      line SGC7901 against DDP-induced apoptosis, inhibition of autophagy can promote
      apoptosis, and combination therapy with DDP and chloroquine may be a promising
      therapeutic strategy for gastric cancer. 

PMID- 24083727
TI  - Ultrasound score to select subcentimeter-sized thyroid nodules requiring
      ultrasound-guided fine needle aspiration biopsy in eastern China.
AB  - Ultrasound-guided fine needle aspiration biopsy (FNAB) is a costly diagnostic
      item with a low yield in identifying the tiny proportion of nodules that actually
      represent malignant disease. Our aim through this study was to obtain an
      ultrasound (US) score for selecting subcentimeter-sized thyroid nodules requiring
      FNAB in eastern China. Some 248 patients for a total of 270 thyroid nodules less
      than 1 cm in diameter underwent FNAB and subsequent surgery from January 2006 to
      March 2012 at our hospital. The clinicopathological and US data from all the
      nodules were analyzed retrospectively. An US score was developed on the basis of
      independent predictive factors for malignancy. Irregular shape, hypoechogenicity,
      no well-defined margin, presence of calcifications and ratio between antero
      posterior and transversal diameters (AP/TR) >=1 were independent predictive
      factors for malignancy on logistic regression analysis. US score were
      statistically significant, with <=2 favoring benignancy with an 80.3% sensitivity
      and a 72.7% specificity. US score is useful for differentiating between malignant
      and benign subcentimeter-sized thyroid nodules. We suggest FNAB for nodules when
      the US score is higher than 2. 

PMID- 24083729
TI  - Limited diagnostic value of microRNAs for detecting colorectal cancer: a meta
      analysis.
AB  - BACKGROUND: MicroRNAs have been demonstrated to play important roles in the
      development and progression of colorectal cancer. Several studies utilizing
      microRNAs as diagnostic biomarkers for colorectal cancer (CRC) have been
      reported. The aim of this meta-analysis was to comprehensively and quantitatively
      summarize the diagnostic value of microRNAs for detecting colorectal cancer.
      METHODS: We searched PubMed, Embase and Cochrane Library for published studies
      that used microRNAs as biomarkers for the diagnosis of colorectal cancer. Summary
      estimates for sensitivity, specificity and other measures of accuracy of
      microRNAs in the diagnosis of colorectal cancer were calculated using the
      bivariate random effects model. A summary receiver operating characteristic
      (SROC) curve was also generated to summarize the overall effectiveness of the
      test. RESULT: Thirteen studies from twelve published articles met the inclusion
      criteria and were included. The overall sensitivity, specificity, positive
      likelihood ratio, negative likelihood ratio and diagnostic odd ratio of microRNAs
      for the diagnosis of colorectal cancer were 0.81 (95%CI: 0.79-0.84), 0.78 (95%CI:
      0.75-0.82), 4.14 (95%CI: 2.90- 5.92), 0.24 (95%CI: 0.19-0.30), and 19.2 (95%CI:
      11.7-31.5), respectively. The area under the SROC curve was 0.89. CONCLUSIONS:
      The current evidence suggests that the microRNAs test might not be used alone as
      a screening tool for CRC. Combining microRNAs testing with other conventional
      tests such as FOBT may improve the diagnostic accuracy for detecting CRC.

PMID- 24083728
TI  - Characteristics and treatment outcomes of patients with malignant transformation
      arising from mature cystic teratoma of the ovary: experience at a single
      institution.
AB  - BACKGROUND: Malignant transformation arising in mature cystic teratoma (MCT) is
      one of the most serious complications of MCT. Squamous cell carcinoma is the most
      common malignant change. Some clinical findings such as advanced age group and
      large tumor size are significant risk factors of malignant transformation. This
      study was conducted in order to evaluate characteristics, cell types, treatment
      and outcome of malignant transformation arising from dermoid cysts in our
      institution. MATERIALS AND METHODS: A retrospective chart review was performed.
      General characteristics, operative data, procedure, operative finding and
      operative outcome were analyzed. Statistical assessment was performed with SPSS
      version 17.0, using mean, mode, median and percentage to describe those data.
      RESULTS: During the 10 years period, 11 cases of malignant transformation from a
      total of 753 cases (1.46% incidence) of MCT were reviewed. Mean age of the
      patients was 41.2 years (SD 4.34, range 24-70). The most common presenting
      symptom was a palpable mass (8 cases; 72.7%). Primary surgical staging was
      performed in 4 patients (36.4%). Re-staging was conducted in the other 4.
      Complete cytoreduction was obtained in 45.5% (5 cases) and optimal surgical
      resection was obtained in 36.4% (4 cases). Mean tumor size was 14.1 cm. (SD 1.55,
      range 6-20). Squamous cell carcinoma was found in 36.4% (4 cases) and mucinous
      cancer in the other 4. More than half of them were stage Ia (54.5%, 6 cases). All
      patients whose stage more than Ia received chemotherapy (45.5%). Mean disease
      free survival was 5.53 years (1.32, 0.3-10). CONCLUSION: According to our study,
      the incidence of malignant transformation was consistent with previous studies.
      The common malignant transformation histologic types are both squamous and
      mucinous carcinoma which differed from previous reports. Early detection for
      early stage disease and optimal surgery are important for long term survival.

PMID- 24083730
TI  - Community health worker hepatitis B education for Cambodian American men and
      women.
AB  - BACKGROUND: Cambodian Americans have high rates of chronic hepatitis B virus
      (HBV) infection and liver cancer. There is very limited information about the
      utility of community health worker (CHW) approaches to cancer education for Asian
      American men. We have previously reported our positive findings from a trial of
      CHW education about HBV for Cambodian Americans who had never been tested for
      HBV. This report describes similarities and differences between the outcomes of
      our CHW HBV educational intervention among Cambodian American men and women.
      METHODS: The study group for this analysis included 87 individuals (39 men and 48
      women) who were randomized to the experimental (HBV education) arm of our trial,
      participated in the CHW educational intervention, and provided follow-up data six
      months post-intervention. We examined HBV testing rates at follow-up, changes in
      HBV-related knowledge between baseline and follow-up, and barriers to HBV testing
      (that were reported to CHWs) by gender. RESULTS: At follow-up, 15% of men and 31%
      of women reported they had received a HBV test (p=0.09). HBV-related knowledge
      levels increased significantly among both men and women. With respect to HBV
      testing barriers, women were more likely than men to cite knowledge deficits, and
      men were more likely than women to cite logistic issues. DISCUSSION: Our study
      findings indicate that CHW interventions can positively impact knowledge among
      Cambodian American men, as well as women. They also suggest CHW interventions may
      be less effective in promoting the use of preventive procedures by Cambodian
      American men than women. Future CHW research initiatives should consider
      contextual factors that may differ by gender and, therefore, potentially
      influence the relative effectiveness of CHW interventions for men versus women.

PMID- 24083731
TI  - Intensity-modulated radiotherapy combined with endocrine therapy for intermediate
      and advanced prostate cancer: long-term outcome of Chinese patients.
AB  - AIM: The aim of this study was to evaluate acute adverse events and efficacy of
      three-dimensional intensity- modulated radiotherapy (IMRT) combined with
      endocrine therapy for intermediate and advanced prostate cancer. METHODS: Sixty
      seven patients were treated with three-dimensional IMRT combined with maximum
      androgen blockade. The correlation between radiation-induced rectal injury and
      clinical factors was further analyzed. RESULTS: After treatment, 21 patients had
      complete remission (CR), 37 had partial remission (PR), and nine had stable
      disease (SD), with an overall response rate of 86.5%. The follow-up period ranged
      from 12.5 to 99.6 months. Thirty-nine patients had a follow-up time of >= five
      years. In this group, three-year and five-year overall survival rates were 89%
      and 89.5%, respectively; three-year and five-year progression-free survival rates
      were 72% and 63%. In univariate analyses, gross tumor volume was found to be
      prognostic for survival (chi2 = 5.70, P = 0.037). Rates of leucopenia and anemia
      were 91.1% and 89.5%, respectively. Two patients developed acute liver injury,
      and a majority of patients developed acute radiation proctitis and cystitis,
      mainly grade 1/2. Tumor volume before treatment was the only prognostic factor
      influencing the severity of acute radiation proctitis (P < 0.05). CONCLUSIONS:
      IMRT combined with endocrine therapy demonstrated promising efficacy and was well
      tolerated in patients with intermediate and advanced prostate cancer.

PMID- 24083732
TI  - An Australian retrospective study to evaluate the prognostic role of p53 and
      eIF4E cancer markers in patients with head and neck squamous cell carcinoma
      (HNSCC): study protocol.
AB  - Complete surgical resection of the primary tumour is a crucial predictive step
      for head and neck squamous cell carcinoma (HNSCC), because incomplete resection
      may lead to increase in the recurrence rate. Molecular cancer markers have been
      investigated as potential predictors of prognosis marker, to identify patients
      who are at high risk of local recurrence. This retrospective study aimed to
      determine the prognostic correlation between p53 and eIF4E expression and
      clinical characteristics, recurrence and overall survival. Forty eight HNSCC
      patients were selected between 2006 and 2009 diagnosed at the Royal Darwin
      Hospital, Darwin, Northern Territory, Australia. Out of 48, only those 24 with
      negative surgical margins with hematoxylin and eosin (HandE) were chosen for
      further analysis. A total of 77 surgical margins were obtained and subsequently
      analysed by immunohistochemical (IHC) staining with monoclonal p53 and polyclonal
      eIF4E antibodies. Contingency table and chi2-test were used to investigate the
      correlation between p53 and eIF4E expression and clinical characteristics,
      recurrence and overall survival of the HNSCC patients. The follow up period was
      74 months (range 1-74 months). The Kaplan-Meier method was used to generate
      recurrence and survival curves. This is a first retrospective study of Northern
      Territory patients, including Indigenous and non-Indigenous Australians.
      Molecular study of surgical margins could help to identify patients with and
      without clear margins after surgery and help in choice of the most appropriate
      adjuvant treatment for HNSCC patients. 

PMID- 24083733
TI  - Age at diagnosis in bladder cancer: does opium addiction play a role?
AB  - BACKGROUND: Bladder cancer is a major health problem, especially among men. Opium
      addiction can be an important risk factor. One important question is whether it
      can affect the age of onset of bladder cancer .We performed this study to
      evaluate this question. MATERIALS AND METHODS: In a cross-section study, records
      of patients diagnosed with bladder carcinoma in Shahid Labbafinejad Medical
      Center, within 1999-2008 were included. Data were extracted from records
      regarding age at onset, gender, smoking status, and opioid addiction and analyzed
      with SPSS 13. RESULTS: Within 10 years, 920 cases were diagnosed with bladder
      cancer of which 97 percent were transitional cell carcinoma. In 698 cases, opium
      addiction status was recorded in 21.3% (n=149). Age at diagnosis was 59.7+/-11.51
      (median: 60) among opioid addicts which was significantly lower than non- addicts
      (63.1+/-13.65, Median: 65) (P<0.001). CONCLUSIONS: Opium addiction can decrease
      the age of onset of bladder cancer.

PMID- 24083734
TI  - Pyogenic liver abscess as a warning sign for primary liver cancer: a nationwide
      population-based study.
AB  - BACKGROUND: There have been no large-scale population-based studies to estimate
      the subsequent risk of primary liver cancer (PLC) among patients with pyogenic
      liver abscess (PLA). This study aimed to provide relevant data. MATERIALS AND
      METHODS: The Taiwan Longitudinal Health Insurance Database for the years 2000 and
      2005 was used. The PLA group were adult inpatients who were newly diagnosed with
      PLA from 2000 to 2008. The control group was randomly selected and matched with
      the PLA group in terms of age, sex, and date in which medical treatment was
      sought other than for PLA. RESULTS: There were 1,987 patients each in the PLA and
      control groups. In total, 56 had PLC, 48 (2.4%, 601.5 per 100,000 person-years)
      from the PLA group, and 8 from the control group. After adjusting for potential
      covariates, the hazard ratio of PLC for the PLA group was 3.4 times that of the
      control group (95% confidence interval = 1.6-7.3, p <0.001). The PLC risk for the
      PLA group was significantly higher within the first year after PLA diagnosis
      (hazard ratio: 35.4) as compared with the control group and became insignificant
      (hazard ratio: 2.0, 95% confidence interval = 0.8-4.9) more than one year after
      PLA diagnosis. CONCLUSIONS: Patients with PLA have a higher rate of PLC than
      matched controls, especially within the first year after the diagnosis of PLA,
      suggesting PLA is a warning sign for PLC.

PMID- 24083735
TI  - Breastfeeding and the risk of childhood Hodgkin lymphoma: a systematic review and
      meta-analysis.
AB  - PURPOSE: Numerous observational epidemiological studies have evaluated
      associations between breastfeeding and the risk of childhood Hodgkin lymphoma;
      however, the existing results are inconsistent. We therefore conducted a
      systematic review and meta-analysis. METHODS: Medical literature was searched in
      the Pubmed and Embase databases to identify all English-language relevant studies
      up to April 10, 2013. Reference lists were thereafter hand-searched for
      additional articles. Studies that reported relative risk ratios (RRs) or odds
      ratios (ORs) with 95% confidence intervals (CIs) were included. This meta
      analysis was conducted in accordance with the guidelines for the meta-analysis of
      observational studies in epidemiology. RESULTS: We finally included 10 case
      control studies in our meta-analysis, involving 1,618 childhood Hodgkin lymphoma
      cases and 8,181 controls. Overall, we did found a borderline significant
      association between breastfeeding and reduced risk of childhood Hodgkin lymphoma
      comparing ever breastfed children to never breastfed children (pooled OR =0.79;
      95%CI, 0.58-1.08; P=0.13), with limited evidence for between-study heterogeneity
      (P =0.12, I2 = 35.70%). CONCLUSION: There is limited evidence for an inverse
      association between breastfeeding and risk of childhood Hodgkin lymphoma.

PMID- 24083736
TI  - GSTT1 null and MPO -463G>a polymorphisms and carboplatin toxicity in an Indian
      population.
AB  - Carboplatin, a second generation platinum drug, is widely used to treat different
      types of cancers. However, myelosuppression remains a major consideration in its
      use. Genetic polymorphisms of enzymes involved in drug disposition can influence
      therapeutic outcome. The homozygous null deletion of phase II metabolic gene
      GSTT1 that abolishes its xenobiotic- detoxifying ability may be associated with
      carboplatin toxicity. Further, since carboplatin generates oxidative stress,
      polymorphisms of oxidative stress genes that regulate the cellular level of free
      radicals may have important roles in generating drug- related adverse effects. We
      here investigated the null polymorphism of GSTT1, and the -463G>A promoter
      polymorphism of oxidative stress gene myeloperoxidase (MPO) for carboplatin
      toxicity in a population of northern India. Cancer patients who were treated with
      carboplatin, and developed toxicity was considered. The study group comprised of
      10 patients who developed therapy- related adverse effects. Peripheral blood was
      taken from patients for DNA isolation. GSTT1 null genotype was determined by
      conducting duplex PCR and MPO-463 G>A was determined by PCR followed by RFLP.
      Hematologic toxicity was experienced by 5 patients, 2 of them had grade 3 and 4
      toxicity and 3 others had grade 2 toxicity. They also had gastrointestinal (GI)
      toxicity. Remaining 5 individuals developed GI toxicity but no hematological
      toxicity. While GG homozygous of MPO was present in majority of patients having
      hematologic toxicity (in 4 out of 5 individuals), one A allele (AG genotype) was
      present in 4 patients who did not have any hematological toxicity. Thus variant A
      allele of MPO -463G>A may be related to lower hematological toxicity. These
      preliminary data, however, are required to be confirmed in larger studies along
      with other relevant polymorphisms. 

PMID- 24083737
TI  - Prevalence of and factors associated with osteoporosis among Korean cancer
      survivors: a cross-sectional analysis of the Fourth and Fifth Korea National
      Health and Nutrition Examination Surveys.
AB  - BACKGROUND: Identifying and managing osteoporosis among cancer survivors is an
      important issue, yet little is known about the bone health of cancer survivors in
      Korea. This study was designed to measure the prevalence of osteoporosis and to
      assess related factors among Korean cancer survivors. MATERIALS AND METHODS: This
      study was designed as a cross-sectional analysis. Data were obtained from dual
      energy X-ray absorptiometry measurement of the lumbar vertebrae and femoral neck,
      and from standardized questionnaires among 556 cancer survivors and 17,623 non
      cancer controls who participated in the Fourth and Fifth Korea National Health
      and Nutrition Examination Surveys (2008-2011). We calculated adjusted proportions
      of osteoporosis in non-cancer controls vs. cancer survivors, and we performed
      multivariate logistic regression analysis. RESULTS: The prevalence of
      osteoporosis among cancer survivors was significant higher than that of the non
      cancer controls after adjusting for related factors. Furthermore, osteoporosis
      among cancer survivors was higher in elderly subjects (60-69 years : adjusted
      odds ratio (aOR) 3.04, 95% CI : 1.16-8.00, >=70 years : aOR 6.60, 95% CI 2.20
      19.79), in female cancer survivors (aOR: 7.03, 95% CI: 1.88-26.28), and in a
      group with lower monthly income (aOR: 3.38, 95% CI: 1.31-8.71). In male cancer
      survivors, underweight and lower calcium intake were risk factors. CONCLUSIONS:
      These data suggest that the osteoporosis among cancer survivors varies according
      to non-oncologic and oncologic factors. Effective screening should be applied,
      and a sufficient and comprehensive management should be matched to individual
      cancer survivors early after cancer treatment.

PMID- 24083738
TI  - Does immunohistochemistry provide additional prognostic data in gastrointestinal
      stromal tumors?
AB  - BACKGROUND: To investigate the predictive and prognostic effects of
      clinicopathologic and immunohistochemical (IHC) features in patients with
      gastrointestinal stromal tumours (GISTs). MATERIALS AND METHODS: Fifty-six
      patients who were diagnosed with GIST between 2002 and 2012 were retrospectively
      evaluated. Relationships between clinicopathologic/immunohistochemical factors
      and prognosis were investigated. RESULTS: Median overall survival (OS) of the
      whole study group was 74.9 months (42.8-107.1 months), while it was 95.2 months
      in resectable and 44.7 months in metastatic patients respectively (p=0.007).
      Epitheliolid tumor morphology was significantly associated with shortened OS as
      compared to other histologies (p=0.001). SMA(+) tumours were significantly
      correlated with low (<10/50HPF) mitotic activity (p=0.034). Moreover, SMA(+)
      patients tended to survive longer and had significantly longer disease-free
      survival (DFS) times than SMA (-) patients (37.7 months vs 15.9 months; p=0.002).
      High Ki-67 level (>=30%) was significantly associated with shorter OS (34 vs 95.2
      months; 95%CI; p=0.001). CD34 (-) tumours were significantly associated with low
      proliferative tumours (Ki-67<%10) (p=0.026). Median PFS (progression-free
      survival) of the patients who received imatinib was 36 months (27.7-44.2 months).
      CD34 (-) patients had significantly longer PFS times than that of negative
      tumours; (50.8 vs 29.8 months; p=0.045). S100 and desmin expression did not play
      any role in predicting the prognosis of GISTs. Multivariate analysis demonstrated
      that >=10/50HPF mitotic activity/HPF was the only independent factor for risk of
      death in GIST patients. CONCLUSIONS: Despite the negative prognostic and
      predictive effect of high Ki-67 and CD34 expression, mitotic activity remains the
      strongest prognostic factor in GIST patients. SMA positivity seems to affect GIST
      prognosis positively. However, large-scale, multicenter studies are required to
      provide supportive data for these findings.

PMID- 24083739
TI  - Risk factors for early and late intrahepatic recurrence in patients with single
      hepatocellular carcinoma without macrovascular invasion after curative resection.
AB  - BACKGROUND: Prognostic factors of postoperative early and late recurrence in
      patients with hepatocellular carcinoma (HCC) undergoing curative resection remain
      to be clarified. The aim of this study was to identify risk factors for
      postoperative early (<= 2 year) and late (> 2 year) intrahepatic recurrences in
      patients with single HCCs without macrovascular invasion. METHODS: A total of 280
      patients from December 2004 to December 2007 were retrospectively included in
      this study. Intrahepatic recurrence was classified into early (<= 2 year) and
      late (> 2 year) and the Chi-Square test or Fisher's exact test and multivariate
      logistic regression analysis were performed to determine significant risk
      factors. RESULTS: During the follow-up, 124 patients had intrahepatic recurrence,
      early and late in 82 and 42 patients, respectively. Multivariate logistic
      regression analysis showed that microvascular invasion (p=0.006, HR: 2.397, 95%
      CI: 1.290-4.451) was the only independent risk factor for early recurrence, while
      being female (p = 0.031, HR: 0.326, 95% CI: 0.118-0.901), and having a high
      degree of cirrhosis (P=0.001, HR: 2.483, 95% CI: 1.417-4.349) were independent
      risk factors for late recurrence. CONCLUSIONS: Early and late recurrence of HCC
      is linked to different risk factors in patients with single HCC without
      macrovascular invasion. This results suggested different emphases of strategies
      for prevent of recurrence after curative resection, more active intervention
      including adjuvant therapy, anti-cirrhosis drugs and careful follow-up being
      necessary for patients with relevant risk factors.

PMID- 24083741
TI  - Overall survival of Filipino patients with squamous cell carcinoma of the head
      and neck: a single-institution experience.
AB  - This paper is the first to present the incidence and overall survival of patients
      with squamous cell carcinoma of the head and neck (SCCHN) from the extreme
      northern part of the Philippines. We retrospectively retrieved the records of
      patients with histologically-confirmed squamous cell carcinoma of the oral
      cavity, oropharynx, hypopharynx and larynx at the Mariano Marcos Memorial
      Hospital and Medical Center, Ilocos Norte, Philippines, from 2003 to 2012 and
      analysed prognostic factors associated with survival. Of the 150 cases, only 80
      (53.3%) were still living when the study was terminated. Median age at initial
      diagnosis was 61.5 years and the male to female ratio was 7:3. The majority of
      the cases had tumours in the oral cavity (50.7%), followed by the larynx (36.7%).
      Sex (log rank=1.94, p value/alpha=0.16), tumor site (log rank=0.02, p
      value/alpha=0.90), tumor grade (log rank=1.74, p value/alpha=0.42), and node
      stage (log rank=0.07, p value/alpha=0.80) were not shown to be associated with
      the survival of our cases. Only 45 (30.0%) had no regional lymph node involvement
      (N0) at presentation and 12 (8.0%) had already developed distant metastases.
      Among the 150 patients, 71 (47.3%) were not able to receive treatment of any
      kind. Oddly, treatment (log rank=1.65, p value/alpha=0.20) was also shown to be
      not associated with survival. The survival rate of those who underwent surgery,
      radiotherapy, or both was not statistically different from those who did not
      receive any treatment. Only the tumor stage (log rank=4.51, p value/alpha=0.03)
      was associated with patient survival. The overall mean survival was 49.3 months,
      with survival rate diminishing from 88.3% during the 1st year to 1.80% by end of
      the study. This relatively low survival rate of our cases only reflects their
      poor access to quality diagnostic and treatment facilities. 

PMID- 24083740
TI  - Research on the relationship between serum levels of inflammatory cytokines and
      non-small cell lung cancer.
AB  - AIMS: This study was conducted to evaluate the levels of TNF-alpha, IL-6, IL-8
      and VEGF in serum of patients with non- small cell lung cancer, for assessing
      their possible diagnostic and prognostic roles. METHODS: We enrolled 48 patients
      newly diagnosed with non-small cell lung cancer and 40 healthy controls. TNF-
      alpha, IL-6 and IL-8 levels were measured in the serum of all the subjects with
      specific radioimmunoassay kits, while EGF was analyzed by sandwich enzyme
      immunoassay techniques. RESULTS: A statistically significant difference was
      observed between lung cancer patients and the control group regarding the values
      of TNF-alpha, IL-6, IL-8 and VEGF in serum. Moreover, TNF-alpha, IL-8 and VEGF
      levels were higher in patients with advanced stages compared to early stages. In
      addition, higher serum levels of TNF-alpha, IL-6, IL-8 and VEGF were found in
      smokers than in non-smokers, both in patients and controls. CONCLUSION: Serum
      levels of TNF-alpha, IL-6, IL-8 and VEGF were all elevated in lung cancer
      patients, suggesting that inflammatory cytokines could be jointly used as a
      screening tool. Though TNF-alpha, IL-8 and VEGF levels were related to advanced
      disease, long-term survival studies of NSCLC patients should be performed to
      confirm whether they can act as biomarkers of advanced disease. In addition,
      smoking would be an important contributor to the processes of inflammation and
      lung cancer.

PMID- 24083742
TI  - GPR48 promotes multiple cancer cell proliferation via activation of Wnt
      signaling.
AB  - The key signaling networks regulating cancer cell proliferation remain to be
      defined. The leucine-rich repeat containing G-protein coupled receptor 48 (GPR48)
      plays an important role in multiple organ development. In the present study, we
      investigated whether GPR48 functions in cancer cells using MCF-7, HepG2, NCI-N87
      and PC-3 cells. We found that GPR48 overexpression promotes while its knockdown
      using small interfering RNA oligos inhibits cell proliferation. In addition,
      Wnt/beta-catenin signaling was activated in cells overexpressing GPR48.
      Therefore, our results indicated that GPR48 activates Wnt/beta-catenin signaling
      to regulate cancer cell proliferation. 

PMID- 24083743
TI  - Subtypes of white blood cells in patients with prostate cancer or benign
      prostatic hyperplasia and healthy individuals.
AB  - BACKGROUND: This study aimed to evaluate the baseline white blood cell (WBC),
      neutrophil, lymphocyte, monocyte, basophil, eosinophil count, total prostate
      specific antigen (TPSA), free PSA (FPSA) level, neutrophil- to-lymphocyte and
      neutrophil-to-monocyte ratios among patients with prostate cancer and benign
      prostatic hyperplasia (BPH), as well as healthy individuals. MATERIALS AND
      METHODS: 2005-2012 laboratory files of 160 patients with prostate cancer at
      Kayseri Training and Research Hospital, Oncology Outpatient Clinic, 285 patients
      who were pathologically diagnosed with BPH in Urology Outpatient Clinic and 200
      healthy individuals who were admitted to Internal Medicine Outpatient Clinic were
      retrospectively analyzed. Baseline WBC, neutrophil, lymphocyte, monocyte,
      basophil, eosinophil count, TPSA, FPSA level, neutrophil-to-lymphocyte ratio and
      neutrophil-to-monocyte ratio were recorded and compared across groups. RESULTS:
      Patients with prostate cancer had a lower lymphocyte level compared to the
      patients with BPH and healthy controls (p<0.001). The mean monocyte count,
      leukocyte-to-monocyte ratio, and leukocyte-to-lymphocyte ratio were higher in
      patients with prostate cancer, but without significance. The mean WBC and
      leukocyte count were lower in patients with prostate cancer, but again without
      statistical significance (p=0.130). The mean TPSA and FPSA were 39.4 and 5.67,
      respectively in patients with prostate cancer, while they were 5.78 and 1.28 in
      patients with BPH. There was a significant difference in the mean TPSA and FPSA
      levels between the patient groups (p<0.001). CONCLUSIONS: Our study results
      showed that patients with prostate cancer had a lower level of lymphocytes,
      neutrophils and WBCs and a higher level of monocytes with a significant
      difference in lymphocyte count, compared to healthy controls. We suggest that
      lymphocyte count may be used in combination with other parameters in the
      diagnosis of prostate cancer, thanks to its ease of assessment.

PMID- 24083744
TI  - Alcohol Consumption and Breast Cancer Survival: A Meta- analysis of Cohort
      Studies.
AB  - BACKGROUND AND OBJECTIVES: Evidence for associations between alcohol consumption
      with breast cancer survival are conflicting, so we conducted the present meta
      analysis. METHODS: Comprehensive searches were conducted to find cohort studies
      that evaluated the relationship between alcohol consumption with breast cancer
      survival. Data were analyzed with meta-analysis software. RESULTS: We included 25
      cohort studies. The meta-analysis results showed that alcohol consumption was not
      associated with increased breast cancer mortality and recurrence after pooling
      all data from highest versus lowest comparisons. Subgroup analyses showed that
      pre-diagnostic or post-diagnostic consumpotion, and ER status did not affect the
      relationship with breast cancer mortality and recurrence. Although the
      relationships of different alcohol consumption with breast cancer mortality and
      recurrence were not significant, there seemed to be a dose-response relationship
      of alcohol consumption with breast cancer mortality and recurrence. Only alcohol
      consumption of >20 g/d was associated with increased breast cancer mortality, but
      not with increased breast cancer recurrence. CONCLUSION: Although our meta
      analysis showed alcohol drinking was not associated with increased breast cancer
      mortality and recurrence, there seemed to be a dose-response relationship of
      alcohol consumption with breast cancer mortality and recurrence and alcohol
      consumption of >20 g/d was associated with increased breast cancer mortality.

PMID- 24083745
TI  - Phase II study on Javanica oil emulsion injection (Yadanzi(r)) combined with
      chemotherapy in treating patients with advanced lung adenocarcinoma.
AB  - PURPOSE: To investigate the efficacy and safety of Javanica oil emulsion
      injection (Yadanzi(r)) combined with pemetrexed and platinum (PP) for treating
      patients with advanced lung cancer. PATIENTS AND METHODS: From June 2011 to June
      2013, we recruited 58 patients with advanced lung cancer, and divided them into
      two groups. Twenty eight patients received Yadanzi(r) (from ZheJiang Jiuxu
      Pharmaceutical Co., Ltd.) together with PP chemotherapy (combined group), while
      the others were given only PP chemotherapy (control group). After two cycles of
      treatment, efficacy and safety of treatment were evaluated. RESULTS: The overall
      response rate [(CR+PR+SD)/(CR+PR+SD+PD)] of the combined group was higher than
      that of control group (89.7% vs. 86.2%, p>0.05). Regarding rate of life
      improvement, it was 82.8% in combined group, and 51.7% in the control group
      (p<0.05). In terms of side effects, leukopenia in combined group was less
      frequent than that in control group (p<0.05). More patients in the control group
      were found to suffer liver toxicity. CONCLUSIONS: Javanica oil emulsion injection
      combined with chemotherapy could be considered as a safe and effective regimen in
      treating patients with advanced lung adenocarcinoma. It can improve the quality
      of life and reduce the possibility of leukopenia. Further clinical trials with a
      large sample size should be conducted to confirm whether addition of Yadanzi(r)
      to chemotherapy could increase the response rate, reduce toxicity, enhance
      tolerability and improve quality of life for patients with advanced lung cancer.

PMID- 24083746
TI  - Challenges in volunteering from cancer care volunteers perspectives.
AB  - The involvement of non-government organizations (NGOs) and support groups has
      helped strengthen public health services in addressing cancer care burden. Owing
      to the contribution of volunteers in cancer care, this article documents a
      qualitative study that examined challenges in attracting and retaining cancer
      care volunteers as part of the effort to develop a volunteer recruitment model.
      Data were collected through three focus group discussions involving 19 cancer
      support group members in Malaysia. Findings of the study revealed that mobility
      and locality appeared to be significant in Malaysian context, while the need for
      financial support and time flexibility are challenges faced by cancer support
      groups to attract and retain volunteers. The findings imply that cancer care
      initiatives can benefit from more local volunteers but at the same time these
      volunteers require flexibility and financial support to sustain their engagement.

PMID- 24083747
TI  - Clinical study on mannan peptide combined with TP regimen in treating patients
      with non-small cell lung cancer.
AB  - PURPOSE: To investigate short-term response rate, quality of life and toxicities
      of mannan peptide combined with TP regimen in treating patients with non-small
      cell lung cancer (NSCLC). PATIENTS AND METHODS: Forty one patients with NSCLC
      were divided into an experimental group treated with TP regimen combined with
      mannan peptide (21 patients) and a control group treated with TP alone (20
      patients). RESULTS: Response rates were 61.9% (13/21) for the experimental and
      60% (12/20) for the control group (p>0.05). Regarding toxicity, white blood cell
      decreased more frequently in the control group (65%, 13/20) than in the
      experimental group (33.3%, 7/21) (p<0.05); nausea and vomiting also occurred more
      frequently in the control group (55%, 11/20 vs 23.8%, 5/21) (p<0.05). In terms of
      quality of life, this index was improved by 57.1% (12/21) and 25% (5/20) in
      experimental and control groups, respectively (p<0.05). CONCLUSIONS: Response
      rate of TP after combined with mannan peptide is mildly increased, while this
      combination alleviates bone marrow suppression as well as nausea and vomiting of
      TP, and improves quality of life when treating patients with NSCLC. However, this
      conclusion should be confirmed by randomized clinical trails.

PMID- 24083748
TI  - Evaluation of quality of life in Turkish patients with head and neck cancer.
AB  - BACKGROUND: In this study, our aim was to investigate the effect of factors, such
      as radiotherapy, the dose of radiotherapy, the region of radiotherapy, the age of
      the patient, performance, co-morbidity, the stage of the disease and the therapy
      modalities on the quality of life of patients with head and neck cancer.
      MATERIALS AND METHODS: Eighty-two patients who were treated by either
      chemoradiotherapy or radiotherapy, at the Cumhuriyet University Faculty of
      Medicine, Department of Radiation Oncology, between February 2007 and September
      2010, for head and neck cancer were included. The quality of life European
      Organisation for Research and Treatment of Cancer, Questionnaire module to be
      used in Quality of Life assessments in Head and Neck Cancer (EORTC QLQ-HandN35)
      questionnaire was conducted in all patients before starting the radiotherapy, in
      the middle, at the end, at 1 month and at 6 months after the treatment. RESULTS:
      According to the questionnaires at the end and at the 6th month after the
      radiotherapy, it was found that the age of the patient, co-morbidity, ECOG
      performance state, localization, type of treatment, the stage of the disease, the
      dose and the region of radiotherapy affect some of the symptom scales for quality
      of life. CONCLUSIONS: Quality of life was affected negatively during and after
      the radiotherapy. However, in the 6th month after the therapy, a significant
      improvement was observed in most symptoms.

PMID- 24083749
TI  - Significance of blood group and social factors in carcinoma cervix in a semi
      urban population in India.
AB  - BACKGROUND: To assess the significance of social factors as risk factors for
      carcinoma cervix and to determine the significance of blood group to prevalence
      of carcinoma cervix in a semi-urban population of Kolar, Karnataka, India.
      MATERIALS AND METHODS: One hundred cases of carcinoma cervix were included in the
      study, along with 200 females of the same ages considered as controls. Case
      details were collected from the hospital record section regarding social factors
      and blood groups and the data were analyzed by descriptive statistical methods.
      RESULTS: Blood group B showed the highest number of cases (55 cases) followed by
      blood group O (29 cases) in carcinoma cervix which was statistically significant
      (p<0.001). Age of marriage between 11 to 20 years showed highest number of
      carcinoma cervix cases (77 cases) and this also was statistically significant
      (p<0.001). Patients with rural background were 75 (p=0.112, odds ratio: 1.54),
      parity of more than or equal to two constituted 96 cases (p=0.006, odds ratio:
      4.07) and Hindu patients were 95 in number (p=0.220, odds ratio: 1.89).
      CONCLUSIONS: Blood group B and age of marriage between 11 and 20 years were
      significantly associated with carcinoma cervix in our population. Region of
      residence, parity and religion presented with a altered risk for carcinoma
      cervix.

PMID- 24083750
TI  - Diagnostic value of protein Ki67 (MIB-1) in atypical pap smears of postmenopausal
      women.
AB  - BACKGROUND: Atrophic epithelium of cervix sampled from postmenopausal women may
      mimic high-grade cervical intraepithelial neoplasia in Papanicolaou-stained (Pap)
      smears. Ki-67 (MIB-1) protein presents on proliferating cells, and percentage of
      cells with positive nuclei provides a reliable tool for rapid evaluation of the
      growth fraction. The aim of this study was to determine the diagnostic value of
      protein Ki67 staining in atypical pap smears of postmenopausal women. METHODS: In
      a case-control setting, pap smears of 75 women with an atypical pap smear (case
      group) and 75 with normal pap smears (controls) were obtained before and after
      estrogen treatment. Afterward, samples were exposed to the monoclonal antibody Ki
      67 (MIB-1) and the immunohistochemically demonstrated Ki-67+ cells were compared.
      RESULTS: Mean ages of cases and controls were 60.4+/-4.5 and 59.9+/-4.3 years
      respectively (P=0.50). There was one (2.7%) positive Ki-67 specimen in the case
      group, without any positive Ki-67 specimen in the control group (P=0.50).
      CONCLUSIONS: Measurement of proliferative activity index in Pap smears restrained
      with MIB1 is a simple, reliable, and cost-effective method for excluding
      negatives. This would imply that it might allow a substantial reduction of
      diagnostic estrogen courses and subsequent Pap smears in postmenopausal women
      with atypical findings.

PMID- 24083751
TI  - Increased serum S-TRAIL level in newly diagnosed stage-IV lung adenocarcinoma but
      not squamous cell carcinoma is correlated with age and smoking.
AB  - BACKGROUND: Lung cancer is the leading cause of cancer mortality in the world.
      Many factors can protect against or facilitate its development. A TNF family
      member TRAIL, has a complex physiological role beyond that of merely activating
      the apoptotic pathway in cancer cells. Vitamin D is converted to its active form
      locally in the lung, and is also thought to play an important role in lung
      health. Our goal was to investigate the possible clinical significance of serum
      sTRAIL and 1,25-dihydroxyvitamin D(3) levels in patients with non-small cell lung
      cancer (NSCLC). MATERIALS AND METHODS: Totals of 18 consecutive adenocarcinoma
      and 22 squamous cell carcinoma patients with stage-IV non-small cell lung cancer
      referred to our institute were included in this study. There were 12 men and 6
      women, with ages ranging from 38 to 97 (mean 60.5) years with adenocarcinoma, and
      20 men and 2 women, with ages ranging from 46 to 80 (mean 65) years with squamous
      cell carcinoma. Serum levels of sTRAIL and 1,25-dihydroxyvitamin D(3) were
      measured in all samples at the time of diagnosis. RESULTS: sTRAIL levels in NSCLC
      patients were higher than in the control group. Although there was no correlation
      between patient survival and sTRAIL levels, the highest sTRAIL levels were
      correlated with age and cigarette smoking in the adenocarcinoma patients. sTRAIL
      level in healthy individuals were correlated with serum 1,25-dihydroxyvitamin
      D(3). CONCLUSIONS: Serum sTRAIL concentrations were increased in NSCLC patients,
      and correlated with age and smoking history, but not with overall survival.

PMID- 24083752
TI  - AZD1480 can inhibit the biological behavior of ovarian cancer SKOV3 cells in
      vitro.
AB  - OBJECTIVE: To study the mechanism of effects of AZD1480 on the SKOV3 ovarian
      cancer cell line. METHODS: The MTT method was used to assess cellular
      proliferation, flow cytometry for cellular apoptosis, the scratch test to
      determine migration, transwell chamber assays to detect cellular invasion, plate
      clone experiments to detect the clone forming ability and Western blotting to
      determine p-STAT3 protein levels. RESULTS: The proliferation rate, migration
      ability, invasiveness and the clone forming ability of SKOV3 cells were reduced
      after treatment with AZD1480, while apoptosis rate and chemotherapeutic
      susceptibility were increased. After treatment with AZD1480 plus cisplatin, the
      apoptosis rate increased significantly while the expression level of p-STAT3
      protein was decreased. CONCLUSION: AZD1480 can inhibit the proliferation,
      invasion, metastasis and clone formation of SKOV3 cells, induce cellulsar
      apoptosis, increase the chemotherapeutic sensitivity and reduce the expression
      level of p-STAT3 protein.

PMID- 24083753
TI  - Knowledge, attitudes and behaviour of women working in government hospitals
      regarding breast self examination.
AB  - BACKGROUND: Breast self examination (BSE), performed regularly every month, is
      one of the most important methods in the early diagnosis of breast cancer. This
      study was performed with the aim of establishing the knowledge, attitudes, and
      behavior of women working in government hospitals within the province of Samsun
      regarding BSE. MATERIALS AND METHODS: This cross-sectional study was conducted
      between January-March 2012, on a total of 550 women (500 health personnel, and 50
      general administration services (GAS) workers) from 7 government hospitals and
      the Cancer Early Diagnosis, Screening, and Education Centre (CEDSEC). Percentages
      were used for the descriptive statistics, and the chi-square test for the
      evaluation of statistical importance. Values of p<0.05 were accepted as
      significant. RESULTS: The mean age of the participants was 36.2+/- 15.3, and
      42.5% were in the 30-39 year old age group, 78.0% being married. Seventy-eight
      point four percent (78.4%) of the health personnel and 76.0% of the GAS workers
      performed BSE. However, the rates of performing BSE regularly every month were
      only 25.6% and 5.0%. Within the health personnel, 1.4% stated that they did not
      perform BSE because they found it unnecessary as they had no history of breast
      cancer in their family, 3.6% did not do so due to fear and stress, 13.2% because
      they forgot, and 14.6% because they had no complaints. Some 22.2% of the health
      personnel and 52.0% of the GAS workers had undergone mammographic evaluation, the
      difference being significant (p<0.05), 84.1% of the health personnel and 61.9% of
      the GAS workers knowing symptoms of breast cancer. CONCLUSIONS: Women in society
      should be brought to a certain level of awareness and knowledge regarding BSE. It
      is of the utmost importance that health personnel, who carry the responsibility
      for counseling and enlightening society, should interiorize the necessary
      knowledge, attitudes and behavior.

PMID- 24083754
TI  - Feasibility study of docetaxel and cyclophosphamide six- cycle therapy as
      adjuvant chemotherapy for Japanese human epidermal growth factor receptor 2
      negative breast cancer patients.
AB  - BACKGROUND: We compared treatment completion rates and safety of docetaxel and
      cyclophosphamide six- cycle therapy (TC6) with docetaxel followed by 5FU,
      epirubicin and cyclophosphamide (T-FEC) therapy in Japanese patients with human
      epidermal growth factor receptor 2 (HER2)-negative breast cancer. MATERIALS AND
      METHODS: We administered TC6 q3w or T-FEC q3w to HER2-negative breast cancer
      patients. The primary endpoint of this trial was toxicity. As second endpoints,
      the treatment completion rate and relative dose intensity were evaluated.
      RESULTS: The TC6 and T-FEC group consisted of 22 and 21 patients, respectively.
      Concerning hematological toxicity, grade 3 or higher adverse reactions included
      neutropenia and febrile neutropenia. As non-hematological adverse events,
      exanthema and peripheral neuropathy were frequently reported in the TC6 group,
      whereas more patients of the T-FEC group reported nausea and vomiting. In TC6,
      the treatment completion rate was 86.4% and the relative dose intensity of
      docetaxel was 93.2%. In T-FEC, the values were 95.2% and 98.9%, respectively.
      CONCLUSIONS: These results suggest that TC6 is tolerable in Japanese, and that
      this regimen can also be performed in outpatient clinics. However, with the TC6
      regimen, the compliance was slightly lower than with the T-FEC regimen, and
      supportive therapy needs to be managed appropriately.

PMID- 24083755
TI  - Schistosomiasis combined with colorectal carcinoma diagnosed based on endoscopic
      findings and clinicopathological characteristics: a report on 32 cases.
AB  - AIMS AND BACKGROUND: To improve understanding of the relationship between
      schistosome-related enteropathy and colorectal carcinoma with particular focus on
      endoscopic findings and clinicopathological characteristics of colonic
      schistosomiasis. MATERIALS AND METHODS: All cases of intestinal schistosomiasis
      diagnosed at West China Hospital, Chengdu, China, between October 2006 and
      October 2012 were included in this study. A total of 179 cases of colonic
      schistosomiasis diagnosed through colonoscopy and pathological examinations were
      collected for analysis and the demographics, symptoms, endoscopic findings and
      clinicopathological characteristics were retrospectively evaluated. RESULTS: Of
      the 179 colonic schistosomiasis patients, 32 combined with colorectal cancer
      (CRC) were found, between the ages of 44 and 85 years (24 males, 75%). These 32
      lesions were classified as 12 endophytic/ulcerative (37.5%), 10
      exophytic/fungating (31.2%), 4 annular (12.5%), 3 giant polypus (9.4%), and 3 IIc
      (superficial depressed type) (9.4%). The segments of rectum and sigmoid colon
      were involved in 19 patients (59.4%) and 6 patients (18.8%), respectively. The
      histopathologic types were classified as follows: 30 well- differentiated
      adenocarcinomas, one mucinous adenocarcinoma and one poorly differentiated
      adenocarcinoma. The pathological findings suggest colorectal malignancy with
      deposited schistosome ova. CONCLUSIONS: Chronic schistosomal infestation has a
      probable etiological role in promoting genesis of colorectal neoplasms.

PMID- 24083756
TI  - Safety assessment of intravenous administration of trastuzumab in 100ml saline
      for the treatment of HER2- positive breast cancer patients.
AB  - BACKGROUND: The infusion rate is considered to affect incidence and severity of
      infusion reactions (IRs) caused by protein formulations. Trastuzumab (TRS) is
      approved for 90-minute infusion as the initial dose followed by 30-minute
      infusion with 250 ml saline. In the study, we evaluated the safety of TRS
      intravenously administered over 30 minutes with 100 ml saline to reduce burden of
      patients, safety of infusion with 250 ml saline already being established.
      MATERIALS AND METHODS: Women with HER2 positive breast cancer, >=18 years and
      >=55% left ventricular ejection fraction (LVEF), were registered in the study.
      Patients received 8mg/kg of TRS 250 ml over 90 minutes followed by 6mg/kg of TRS
      100ml over 30 minutes in a three-week cycle. RESULTS: A total of 31 patients were
      recruited, 24 for adjuvant therapy and seven with metastases. The median age was
      59 years (range 39 to 82). The total number of TRS doses ranged from 5 to 17 with
      the median of 15. Mild IR occurred in two patients at the first dose. However, no
      IR was observed after reducing to 100 ml saline. No decrease of LVEF, increase of
      serum brain natriuretic peptide or any other adverse events were reported.
      CONCLUSIONS: Intravenous infusion of TRS with 100 ml saline over 30 minutes in
      breast cancer patients can be considered safe based on results from the study. It
      can be given on an outpatient basis as with the currently recommended dilution in
      250 ml saline.

PMID- 24083757
TI  - Is FDG -PET-CT a valuable tool in prediction of persistent disease in head and
      neck cancer.
AB  - OBJECTIVES: To evaluate accuracy of FDG-PET CT in prediction of persistent
      disease in head and neck cancer cases and to determine prognostic value of
      metabolic tumor response. MATERIALS AND METHODS: Between 2009 and 2011, 46
      patients with squamous cell carcinoma of head and neck receiving PET-CT were
      treated with definitive radiotherapy, with or without chemotherapy. There were 29
      nasopharyngeal, 11 hypopharyngeal, 3 oropharyngeal and 3 laryngeal cancer
      patients, with a median age of 50.5 years (range 16-84), 32 males and 14 females.
      All patients were evaluated with PET-CT median 3-5 months (2.4-9.4) after
      completion of radiotherapy. RESULTS: After a median 20 months of follow up,
      complete metabolic response was observed in 63% of patients. Suspicious residual
      uptake was present in 10.9% and residual metabolic uptake in 26.0% of patients.
      The overall sensitivity, specificity, positive predictive value and negative
      predictive value of FDG-PET-CT for detection of residual disease was 91% and 81%,
      64% and 96% respectively. Two year LRC was 95% in complete responders while it
      was 34% in non-complete responders. CONCLUSIONS: FDG PET CT is a valuable tool
      for assessment of treatment response, especially in patients at high risk of
      local recurrence, and also as an indicator of prognosis. Definitely more precise
      criteria are required for assessment of response, there being no clear cut uptake
      value indicating residual disease. Futhermore, repair processes of normal tissue
      may consume glucose which appear as increased uptake in control FDG PET CT.

PMID- 24083758
TI  - Hypoxia induced multidrug resistance of laryngeal cancer cells via hypoxia
      inducible factor-1alpha.
AB  - OBJECTIVES: To investigate whether hypoxia has an effect on regulation of
      multidrug resistance (MDR) to chemotherapeutic drugs in laryngeal carcinoma cells
      and explore the role of hypoxia-inducible factor-1alpha (HIF- 1alpha). METHODS:
      Laryngeal cancer cells were cultured under normoxic and hypoxic conditions. The
      sensitivity of the cells to multiple drugs and levels of apoptosis induced by
      paclitaxel were determined by MTT assay and annexin-V/propidium iodide staining
      analysis, respectively. HIF-1alpha expression was blocked by RNA interference.
      The expression of HIF-1alpha gene was detected by real-time quantitative RT-PCR
      and Western blotting. The value of fluorescence intensity of intracellular
      adriamycin accumulation and retention in cells was evaluated by flow cytometry.
      RESULTS: The sensitivity to multiple chemotherapy agents and induction of
      apoptosis by paclitaxel could be reduced by hypoxia (P<0.05). A the same time,
      the adriamycin releasing index of cells was increased (P<0.05). However,
      resistance acquisition subject to hypoxia in vitro was suppressed by down
      regulating HIF-1alpha expression. CONCLUSION: HIF-1alpha could be considered as a
      key regulator for mediating hypoxia-induced MDR in laryngeal cancer cells via
      inhibition of drug-induced apoptosis and decrease in intracellular drug
      accumulation.

PMID- 24083759
TI  - Topical use of recombinant human epidermal growth factor (EGF)-based cream to
      prevent radiation dermatitis in breast cancer patients: a single-blind randomized
      preliminary study.
AB  - BACKGROUND: The purpose of this study was to assess the effectiveness of a
      recombinant human epidermal growth factor (EGF)-based cream for the prevention of
      acute radiation dermatitis in breast cancer patients receiving radiotherapy (RT).
      MATERIALS AND METHODS: Between December 2012 and April 2013, 40 breast cancer
      patients who received postoperative RT were prospectively enrolled in this study
      and randomly assigned to receive human recombinant EGF-based cream (intervention
      group) or general supportive skin care (control group). The grade of radiation
      dermatitis and pain score were examined at weekly intervals during RT and 6 weeks
      after RT completion. RESULTS: All patients completed the planned RT and complied
      well with instructions for applying the study cream and general supportive skin
      care. In the intervention group, radiation dermatitis of maximum grade 3, 2, and
      1 developed in 3 (15%), 11 (55%), and 6 patients (30%), respectively. In
      comparison, in the control group, radiation dermatitis of maximum grade 3, 2, and
      1 developed in 8 (40%), 10 (50%), and 2 patients (10%), respectively. The
      intervention group showed lower incidence of grade 3 radiation dermatitis than
      the control group (p=0.068 in univariate analysis and p=0.035 in multivariate
      analysis). There was no statistically significant difference in the maximal pain
      score between the two groups (p=0.934). CONCLUSIONS: This single-blind randomized
      preliminary study showed that recombinant human EGF-based cream can have a
      beneficial role in preventing or minimizing radiation dermatitis in breast cancer
      patients. To confirm the results of our study, additional studies with a large
      sample size are required.

PMID- 24083760
TI  - Human Papillomavirus vaccination acceptability among female university students
      in South Africa.
AB  - BACKGROUND: The objectives of this present study were to assess the awareness of
      cervical cancer and its risk factors among female undergraduates in South Africa,
      and to determine the their level of acceptability of Human Papillomavirus (HPV)
      vaccination. MATERIALS AND METHODS: This cross-sectional study was conducted in
      March 2013 among 440 full time undergraduate female students. RESULTS: Of those
      students who never had sex (n=163), 96 (58.9%) had ever heard of cervical cancer
      and only 12 students (12.5%) knew that HPV causes cervical cancer. More than a
      third (35.4%) of the students correctly said that sexual intercourse before age
      of 18 years is a risk factor for cervical cancer and 55.2% of the students knew
      about the Pap smear test which is used for screening cervical cancer. The
      majority (77.3%) were willing to accept HPV vaccination. Results revealed that
      students who knew about the Pap smear test, and were aware that having multiple
      sex partners, sexual intercourse before the age of 18 years, smoking and having
      contracted any STDs are risk factors for cervical cancer were more likely to
      accept HPV vaccination compared to other groups. CONCLUSIONS: The general
      knowledge of South African female university students about cervical cancer is
      not sufficient but they have positive attitudes toward getting vaccinated with
      the HPV vaccine.

PMID- 24083761
TI  - Meta-analysis of outcomes compared between robotic and laparoscopic gastrectomy
      for gastric cancer.
AB  - This meta-analysis was performed to evaluate and compare the outcomes of robotic
      gastrectomy (RG) and laparoscopic gastrectomy (LG) for treating gastric cancer. A
      systematic literature search was carried out using the PubMed database, Web of
      Knowledge, and the Cochrane Library database to obtain comparative studies
      assessing the safety and efficiency between RG and LG in May, 2013. Data of
      interest were analyzed by using of Review Manager version 5.2 software (Cochrane
      Collaboration). A fixed effects model or random effects model was applied
      according to heterogeneity. Seven papers reporting results that compared robotic
      gastrectomy with laparoscopic gastrectomy for gastric cancer were selected for
      this meta-analysis. Our meta- analysis included 2,235 patients with gastric
      cancer, of which 1,473 had undergone laparoscopic gastrectomy, and 762 had
      received robotic gastrectomy. Compared with laparoscopic gastrectomy, robotic
      gastrectomy was associated with longer operative time but less blood loss. There
      were no significant difference in terms of hospital stay, total postoperative
      complication rate, proximal margin, distal margin, numbers of harvested lymph
      nodes and mortality rate between robotic gastrectomy and laparoscopic
      gastrectomy. Our meta-analysis showed that robotic gastrectomy is a safe
      technique for treating gastric cancer that compares favorably with laparoscopic
      gastrectomy in short term outcomes. However, the long term outcomes between the
      two techniques need to be further examined. 

PMID- 24083762
TI  - Awareness of Turkish female adolescents and young women about HPV and their
      attitudes towards HPV vaccination.
AB  - BACKGROUND: The aim of the study was to assess the knowledge about HPV and HPV
      vaccines and attitudes towards vaccination among the females aged 9-24 years in
      Turkey. MATERIALS AND METHODS: Self-administered questionnaires were filled out
      individually by the participants covering demographic information, knowledge
      about HPV infection and HPV vaccines, attitudes towards vaccination, and the
      perceptions of them about their parental attitudes about vaccination. RESULTS: Of
      the 408 subjects participating in the study, 41.6% (n=170) had heard of HPV.
      Thirty-three percent (n=136) knew the causal relationship between HPV and
      cervical cancer. Only 27.9% (n=114) of them knew that HPV vaccines can prevent
      cervical cancer. Eleven percent (n=46) of the females participating in the study
      were willing to be vaccinated, and only 1.4% (n=6) were already vaccinated at the
      current time. The main reason listed among the participants who were not willing
      to be vaccinated was lack of information. CONCLUSIONS: Awareness and knowledge of
      Turkish female adolescents and young women about HPV, relation with cervical
      cancer and prevention of cervical cancer by Pap smear and vaccine are still
      limited. If the most important barrier to vaccination, which is reported as lack
      of information, were to be addressed, it would greatly impact the decision-making
      and vaccine acceptance.

PMID- 24083763
TI  - Upregulated Myc expression in N-methyl nitrosourea (MNU)- induced rat mammary
      tumours.
AB  - BACKGROUND: The most common incident cancer and cause of cancer-related deaths in
      women is breast cancer. The Myc gene is upregulated in many cancer types
      including breast cancer, and it is considered as a potential anti-cancer drug
      target. The present study was conducted to evaluate the Myc (gene and protein)
      expression pattern in an experimental mammary tumour model in rats. MATERIALS AND
      METHODS: Thirty six Sprague Dawley rats were divided into: Experimental group (26
      animals), which received the chemical carcinogen N-methyl nitrosourea (MNU) and a
      control group (10 animals), which received vehicle only. c-Myc oncoprotein and
      its mRNA expression pattern were evaluated using immunohistochemistry (IHC) and
      semi-quantitative reverse transcription-polymerase chain reaction (RT-PCR),
      respectively, in normal rat mammary tissue and mammary tumours. The rat
      glyceraldehyde-3-phosphate dehydrogenase (GAPDH) gene was used as internal
      control for semi-quantitative RT-PCR. RESULTS: Histopathological examination of
      mammary tissues and tumours from MNU treated animals revealed the presence of
      premalignant lesions, benign tumours, in situ carcinomas and invasive carcinomas.
      Immunohistochemical evaluation of tumour tissues showed upregulation and
      heterogeneous cellular localization of c-Myc oncoprotein. The expression levels
      of c-Myc oncoprotein were significantly elevated (75- 91%) in all the tumours.
      Semi-quantitative RT-PCR revealed increased expression of c-Myc mRNA in mammary
      tumours compared to normal mammary tissues. CONCLUSIONS: Further large-scale
      investigation study is needed to adopt this experimental rat mammary tumour model
      as an in vivo model to study anti-cancer strategies directed against Myc or its
      downstream partners at the transcriptional or post-transcriptional level.

PMID- 24083764
TI  - Growth, clonability, and radiation resistance of esophageal carcinoma-derived
      stem-like cells.
AB  - OBJECTIVE: To separate/enrich tumor stem-like cells from the human esophageal
      carcinoma cell line OE-19 by using serum-free suspension culture and to identify
      their biological characteristics and radiation resistance. METHODS: OE-19 cells
      were cultivated using adherent and suspension culture methods. The tumor stem
      like phenotype of CD44 expression was detected using flow cytometry. We examined
      growth characteristics, cloning capacity in soft agar, and radiation resistance
      of 2 groups of cells. RESULTS: Suspended cells in serum-free medium formed
      spheres that were enriched for CD44 expression. CD44 was expressed in 62.5% of
      suspended cells, but only in 11.7% of adherent cells. The suspended cells had
      greater capacity for proliferation and colony formation in soft agar than the
      adherent cells. When the suspended and adherent cells were irradiated at 5 Gy, 10
      Gy, or 15 Gy, the proportion of CD44+ suspended cells strongly and weakly
      positive for CD44 was 77.8%, 66.5%, 57.5%; and 21.7%, 31.6%, 41.4%, respectively.
      In contrast, the proportion of CD44+ adherent cells strongly positive for CD44
      was 18.9%, 14.%, and 9.95%, respectively. When the irradiation dose was increased
      to 30 Gy, the survival of the suspended and adherent cells was significantly
      reduced, and viable CD44+ cells were not detected. CONCLUSION: Suspended cell
      spheres generated from OE-19 esophageal carcinoma cells in serum-free stem medium
      are enriched in tumor stem-like cells. CD44 may be a marker for these cells.

PMID- 24083765
TI  - Cervical precancerous lesions and cancer among patients in the gynaecology
      outpatient department at a tertiary hospital in South Africa.
AB  - BACKGROUND: The purpose of this study was to determine proportional rates of
      cervical precancerous lesions and cancer, and associations with socio-demographic
      variables, HIV status, and CD4 cell count. MATERIALS AND METHODS: A retrospective
      comparative study was conducted targeting the medical records of all women over
      age 18 that were diagnosed histologically through colposcopy with cervical
      precancerous lesions and cancer from 1 December 2011 to 30 November 2012.
      RESULTS: A total of 313 patient records were used for data analysis. The average
      age was 39.1 (SD=2.04) years. More than a third (37.1%) of the patients had CIN
      III or cervical cancer. There was a significant association between age, CD4 cell
      count, HIV status, and cervical lesions (p<0.05). Age was found to be an
      influential predictor of cervical lesions (OR=0.67, 95%CI: 0.46-0.98).
      CONCLUSIONS: There exists an association between age and cervical lesions, with
      presentation of cervical precancerous lesions and cervical cancer at a younger
      age among HIV reactive patients. The National Guidelines should be brought in
      line with the National HIV Counseling and Testing Policy to offer Pap smears to
      all sexually active women that test HIV reactive during routine HIV Testing.

PMID- 24083766
TI  - Lgr4 promotes glioma cell proliferation through activation of Wnt signaling.
AB  - The key signaling networks regulating glioma cell proliferation remain poorly
      defined. The leucine-rich repeat containing G-protein coupled receptor 4 (Lgr4)
      has been implicated in intestinal, gastric, and epidermal cell functions. We
      investigated whether Lgr4 functions in glioma cells and found that Lgr4
      expression was significantly increased in glioma tissues. In addition, Lgr4
      overexpression promoted while its knockdown using small interfering RNA oligos
      inhibited glioma cell proliferation. In addition, Wnt/beta-catenin signaling was
      activated in cells overexpressing Lgr4. Therefore, our results revealed that Lgr4
      activates Wnt/beta-catenin signaling to regulate glioma cell proliferation. 

PMID- 24083767
TI  - Inpatients' knowledge about primary liver cancer and hepatitis.
AB  - OBJECTIVE: To assess the level of an inpatient population's awareness about
      hepatitis and primary liver cancer (PLC), the most common type of which is
      hepatocellular carcinoma (HCC), and then to initiate education of this group.
      METHODS: A survey was conducted with 1300 participants within the inpatient unit
      in representative tertiary hospitals in the Chaoshan area of China. Structured
      questionnaires contained demographic data and statements about different aspects
      of liver cancer and hepatitis. The questionnaires were completed by trained
      medical practitioners after they had conducted the interviews. RESULTS: One way
      ANOVA showed that the sample population lacked adequate knowledge about HCC and
      hepatitis. Stepwise multiple regression analysis demonstrated that the
      participant's level of education had the greatest impact on their total knowledge
      score when other variables remained constant. CONCLUSIONS: The study
      demonstrated: a general lack of awareness amongst the participants about the
      preventative strategies, and the management options available for people with
      primary liver cancer and hepatitis; education level was an important factor
      affecting knowledge levels. The demonstrated deficiencies in people's knowledge
      about hepatitis and HCC, and their lack of subsequent protective behaviours are
      likely to play an important role in HCC and hepatitis transmission or prevention.

PMID- 24083768
TI  - Breast self examination practice and breast cancer risk perception among female
      university students in Ajman.
AB  - Breast cancer is the top cancer in women worldwide and its incidence is
      increasing, particularly in developing countries. In the United Arab Emirates
      (UAE), many cases are first diagnosed in later stages and at younger age compared
      to those seen in developed countries. Early detection in order to improve breast
      cancer outcome and survival remains the cornerstone of breast cancer control.
      Performance of breast self examination is one of the important steps for
      identifying breast disease at an early stage, by the woman herself. No
      information has hitherto been available about the frequency of this practice
      among female university students in UAE or about their breast cancer risk
      perception and therefore the present study was conducted in Ajman. It was found
      that 22.7% of the participants practiced BSE but only 3% of them practiced BSE
      monthly. Marital status but not age as significantly associated with age
      likelihood. The most frequent reported barriers for BSE were lack of knowledge,
      considering oneself not at risk and the absence of doctor advice. These factors
      need to be taken into account in intervention efforts. 

PMID- 24083769
TI  - Evaluation of breast self-examination (BSE) application in first and second
      degree relatives of patients with breast cancer.
AB  - BACKGROUND: The aim of this study was to determine beliefs concerning breast self
      examination in first- and second-degree relatives of patients with breast cancer
      and evaluate their breast self-examination (BSE) application. MATERIALS AND
      METHODS: A survey study was conducted in an oncology polyclinic and general
      surgery clinic of a hospital in Ankara, the capital of Turkey with a sample of
      140 women. RESULTS: It was determined that 60.7% of the participants had
      conducted BSE and 48.1% had undergone a clinical breast examination. Perceived
      self- efficacy of the women who performed BSE were significantly higher compared
      with women who did not practice BSE (p<0.001) Furthermore, perceived barriers
      were lower among those who had performed BSE (p<0.001). Logistic regression
      analysis indicated that women who perceived higher self-efficacy (OR: 1.119, 95%
      CI: 1.056- 1.185, p<0.001) and had regular CBE (OR: 8.250, 95% CI: 3.140-21.884,
      p<0.001) and educational status (OR: 5.287, 95% CI: 1.480-18.880, p<0.01) were
      more likely to perform BSE. CONCLUSIONS: Findings from this study indicated that
      perceived barriers, perceived self-efficacy, and educational status could be
      predictors of BSE behavior among the first- and second-degree relatives of
      patients with breast cancer. Therefore, BSE training programs that emphasize self
      efficacy and address perceived barriers are recommended.

PMID- 24083770
TI  - Effect of Reiki on symptom management in oncology.
AB  - Reiki is a form of energy therapy in which the therapist, with or without light
      touch, is believed to access universal energy sources that can strengthen the
      body's ability to heal itself, reduce inflammation, and relieve pain and stress.
      There is currently no licensing for Reiki nor, given its apparent low risk, is
      there likely to be. Reiki appears to be generally safe, and serious adverse
      effects have not been reported. So in this article provides coverage of how to
      use Reiki in oncology services. 

PMID- 24083771
TI  - Challenges and outlook for the UICC-Asian Regional Office.
AB  - At the United Nations High-level Meeting on Non-communicable Disease Prevention
      and Control in 2011 the link between health and socioeconomic issues was raised,
      becoming a global political issue. Health equity is one challenge that has
      hitherto not been addressed directly, although there is a growing shared
      recognition that cancer in Asia is an urgent social issue. At the UICC-ARO we are
      working to promote and widen networks of individuals and organizations in Asia
      and involve them in cooperation for this purpose. As part of our current
      activities, we are addressing the question of the "Economic burden of cancer in
      Asian countries: How should we face the current situation? " from a variety of
      angles and seeking to bring together a wealth of multidisciplinary knowledge
      about cancer in Asia and its related socioeconomic factors. It is essential to
      ensure that the real picture of cancer in Asia, which is currently not accurately
      understood, is conveyed clearly to all concerned, and also that the differences
      between cancer in Asia and in the West are highlighted. 

PMID- 24083772
TI  - What and where for publications by cancer registries in the Asian Pacific? -
      roles for the APJCP in the future.
AB  - The absolute necessity of cancer registration for cancer control planning is well
      accepted. The registry at the national or local level can provide not only
      essential data for cancer incidence, mortality and survival but may also point to
      risk and protective factors and efficacy of interventions by conducting
      epidemiological research. Timely publication of research findings in PubMed
      indexed journals is of the essence, especially in examples that allow free access
      so that the widest dissemination of information can be achieved. The present
      commentary covers the scope of research in Asia or using Asian data in the period
      2008-2013, nearly 40% of a total of over 300 papers being published in the APJCP.
      In order to reach its full potential the registry should incorporate many skills.
      Cooperation for this purpose, whether it be national, regional, Asia-wide or
      international, is a high priority and the International Agency for Research on
      Cancer, together with the National Cancer Institute in Thailand and the
      APOCP/APJCP are staging an Asian Cancer Network Forum in Bangkok in February of
      2014 to allow discussion of ways forward. It is hoped that representatives from
      all regions of Asia will decide to attend and also contribute country reports for
      publication in a special supplement of the APJCP. 

PMID- 24083773
TI  - Importance of patient-physician relationship in cancer prevention: a self
      experience-based survey.

PMID- 24083774
TI  - Robotic prostatectomy in urological surgery: an observership at Weill Medical
      College of Cornell University, New York.

PMID- 24083775
TI  - Energy recovery and emissions of PBDD/Fs and PBDEs from cocombustion of woodchip
      and wastewater sludge in an industrial boiler.
AB  - The emissions of polybrominated dibenzo-pdioxins,dibenzofurans (PBDD/Fs), and
      polybrominated diphenyl ethers (PBDEs) from trial combustion of 10 wt % dried
      industrial wastewater-treatment sludge (IWTS) and 90 wt % woodchip in an
      industrial boiler were investigated and compared to that from woodchip
      combustion. The PBDD/F toxic equivalent (TEQ) andPBDE emissions increased from
      0.121 pg TEQ Nm-3 and 2260 pgNm-3, respectively, of the woodchip combustion to
      0.211 pg TEQNm-3 and 4200 pg Nm-3, respectively, of the trial combustion.PBDD/F
      and PBDE congener profiles of inputs and outputs of the same type of combustion
      were similar; they also show similarity between woodchip and trial combustions,
      revealing that the destruction pathway was little affected by the introduction of
      the IWTS. The fates of PBDD/Fs and PBDEs show that the indigenous pollutants in
      the feed were effectively depleted (>93.5%). The dominant releasing route of
      PBDD/F and PBDE shifted from the stack flue gas of woodchip combustion to the
      ashes of trial combustion. This study demonstrates that co-combustion not only
      handles the fast growing sludge stream but also yields a saving of 26.3% in the
      fuel cost and treatment fees of sludge and ashes.

PMID- 24083776
TI  - Functional analysis of the omega-6 fatty acid desaturase (CaFAD2) gene family of
      the oil seed crop Crambe abyssinica.
AB  - BACKGROUND: Crambe abyssinica produces high erucic acid (C22:1, 55-60%) in the
      seed oil, which can be further increased by reduction of polyunsaturated fatty
      acid (PUFA) levels. The omega-6 fatty acid desaturase enzyme (FAD2) is known to
      be involved in PUFA biosynthesis. In crambe, three CaFAD2 genes, CaFAD2-C1,
      CaFAD2-C2 and CaFAD2-C3 are expressed. RESULTS: The individual effect of each
      CaFAD2 gene on oil composition was investigated through studying transgenic lines
      (CaFAD2-RNAi) for differential expression levels in relation to the composition
      of seed-oil. Six first generation transgenic plants (T1) showed C18:1 increase
      (by 6% to 10.5%) and PUFA reduction (by 8.6% to 10.2%). The silencing effect in
      these T1-plants ranged from the moderate silencing (40% to 50% reduction) of all
      three CaFAD2 genes to strong silencing (95% reduction) of CaFAD2-C3 alone. The
      progeny of two T1-plants (WG4-4 and WG19-6) was further analysed. Four or five
      transgene insertions are characterized in the progeny (T2) of WG19-6 in contrast
      to a single insertion in the T2 progeny of WG4-4. For the individual T2-plants of
      both families (WG19-6 and WG4-4), seed-specific silencing of CaFAD2-C1 and CaFAD2
      C2 was observed in several individual T2-plants but, on average in both families,
      the level of silencing of these genes was not significant. A significant
      reduction in expression level (P < 0.01) in both families was only observed for
      CaFAD2-C3 together with significantly different C18:1 and PUFA levels in oil.
      CONCLUSIONS: CaFAD2-C3 expression is highly correlated to levels of C18:1 (r = 
      0.78) and PUFA (r = 0.75), which suggests that CaFAD2-C3 is the most important
      one for changing the oil composition of crambe.

PMID- 24083777
TI  - Effect of Ser392 phosphorylation on the structure and dynamics of the polybasic
      domain of ADP ribosylation factor nucleotide site opener protein: a molecular
      simulation study.
AB  - ADP ribosylation factor nucleotide site opener (ARNO) as a guanine nucleotide
      exchange factor (GEF) activates small GTPases called ADP ribosylation factors
      (Arfs), which function as molecular switches and regulate a variety of cell
      biological events. ARNO directly interacts with the transmembrane a2-subunit
      isoform of the proton-pumping vacuolar ATPase in an acidification-dependent
      manner, and this interaction plays a crucial role in the regulation of the
      protein degradation pathway. A recent study reported specific interactions of a2N
      with the ARNO375-400 peptide corresponding to the polybasic (PB) domain of ARNO,
      which is a crucial regulatory element in the autoregulation and modulation of Arf
      GEF activity. Interestingly, phosphorylation of Ser392 completely abolishes this
      interaction, and the experimental structure shows significant structural
      rearrangements. To investigate the effect of Ser392 phosphorylation on the
      structure and dynamics of the ARNO375-400 peptide, we employed all atom molecular
      dynamics (MD) simulations of the phosphorylated and unphosphorylated PB domain of
      the ARNO protein. A Hamiltonian-based replica exchange method called biasing
      potential replica exchange MD was used to enhance conformational sampling.
      Simulations predicted that the isolated PB domain is highly flexible, with the C
      terminal region of the unphosphorylated state being unstable. In contrast, Ser392
      phosphorylation increases the overall stability of the peptide. In agreement with
      experimental results, our simulations further support the hypothesis that
      phosphorylation induces disorder to order transitions and provide new insights
      into the structural dynamics of the PB domain. Phosphorylation of Ser392 appears
      to stabilize the C-terminal alpha-helix via formation of salt bridges between
      phospho-Ser392 and Arg390, Lys395, and Lys396. 

PMID- 24083779
TI  - Which activities threaten independent living of elderly when becoming
      problematic: inspiration for meaningful service robot functionality.
AB  - PURPOSE: In light of the increasing elderly population and the growing demand for
      home care, the potential of robot support is given increasing attention. In this
      paper, an inventory of activities was made that threaten independent living of
      elderly when becoming problematic. Results will guide the further development of
      an existing service robot, the Care-O-bot(r). METHOD: A systematic literature
      search of PubMed was performed, focused on the risk factors for
      institutionalization. Additionally, focus group sessions were conducted in the
      Netherlands, United Kingdom and France. In these focus group sessions,
      problematic activities threatening the independence of elderly people were
      discussed. Three separate target groups were included in the focus group
      sessions: (1) elderly persons (n = 41), (2) formal caregivers (n = 40) and (3)
      informal caregivers (n = 32). RESULTS: Activities within the International
      Classification of Functioning domains mobility, self-care, and interpersonal
      interaction and relationships were found to be the most problematic. CONCLUSIONS:
      A distinct set of daily activities was identified that may threaten independent
      living, but no single activity could be selected as the main activity causing a
      loss of independence as it is often a combination of problematic activities that
      is person-specific. Supporting the problematic activities need not involve a
      robotic solution.

PMID- 24083778
TI  - Recommendations from a consensus development workshop on the diagnosis of fetal
      alcohol spectrum disorders in Australia.
AB  - BACKGROUND: Fetal alcohol spectrum disorders (FASD) are underdiagnosed in
      Australia, and health professionals have endorsed the need for national
      guidelines for diagnosis. The aim of this study was to develop consensus
      recommendations for the diagnosis of FASD in Australia. METHODS: A panel of 13
      health professionals, researchers, and consumer and community representatives
      with relevant expertise attended a 2-day consensus development workshop to review
      evidence on the screening and diagnosis of FASD obtained from a systematic
      literature review, a national survey of health professionals and community group
      discussions. The nominal group technique and facilitated discussion were used to
      review the evidence on screening and diagnosis, and to develop consensus
      recommendations for the diagnosis of FASD in Australia. RESULTS: The use of
      population-based screening for FASD was not recommended. However, there was
      consensus support for the development of standard criteria for referral for
      specialist diagnostic assessment. Participants developed consensus
      recommendations for diagnostic categories, criteria and assessment methods, based
      on the adaption of elements from both the University of Washington 4-Digit
      Diagnostic Code and the Canadian guidelines for FASD diagnosis. Panel members
      also recommended the development of resources to: facilitate consistency in
      referral and diagnostic practices, including comprehensive clinical guidelines
      and assessment instruments; and to support individuals undergoing assessment and
      their parents or carers. CONCLUSIONS: These consensus recommendations provide a
      foundation for the development of guidelines and other resources to promote
      consistency in the diagnosis of FASD in Australia. Guidelines for diagnosis will
      require review and evaluation in the Australian context prior to national
      implementation as well as periodic review to incorporate new knowledge.

PMID- 24083780
TI  - Emerging issues and current trends in assistive technology use 2007-2010:
      practising, assisting and enabling learning for all.
AB  - Following an earlier review in 2007, a further review of the academic literature
      relating to the uses of assistive technology (AT) by children and young people
      was completed, covering the period 2007-2011. As in the earlier review, a
      tripartite taxonomy: technology uses to train or practise, technology uses to
      assist learning and technology uses to enable learning, was used in order to
      structure the findings. The key markers for research in this field and during
      these three years were user involvement, AT on mobile mainstream devices, the
      visibility of AT, technology for interaction and collaboration, new and
      developing interfaces and inclusive design principles. The paper concludes by
      locating these developments within the broader framework of the Digital Divide.

PMID- 24083781
TI  - Proteins in action: femtosecond to millisecond structural dynamics of a
      photoactive flavoprotein.
AB  - Living systems are fundamentally dependent on the ability of proteins to respond
      to external stimuli. The mechanism, the underlying structural dynamics, and the
      time scales for regulation of this response are central questions in
      biochemistry. Here we probe the structural dynamics of the BLUF domain found in
      several photoactive flavoproteins, which is responsible for light activated
      functions as diverse as phototaxis and gene regulation. Measurements have been
      made over 10 decades of time (from 100 fs to 1 ms) using transient vibrational
      spectroscopy. Chromophore (flavin ring) localized dynamics occur on the pico- to
      nanosecond time scale, while subsequent protein structural reorganization is
      observed over microseconds. Multiple time scales are observed for the dynamics
      associated with different vibrations of the protein, suggesting an underlying
      hierarchical relaxation pathway. Structural evolution in residues directly H
      bonded to the chromophore takes place more slowly than changes in more remote
      residues. However, a point mutation which suppresses biological function is shown
      to 'short circuit' this structural relaxation pathway, suppressing the changes
      which occur further away from the chromophore while accelerating dynamics close
      to it. 

PMID- 24083782
TI  - Benzazepinones and benzoxazepinones as antagonists of inhibitor of apoptosis
      proteins (IAPs) selective for the second baculovirus IAP repeat (BIR2) domain.
AB  - XIAP is a key regulator of apoptosis, and its overexpression in cancer cells may
      contribute to their survival. The antiapoptotic function of XIAP derives from its
      BIR domains, which bind to and inhibit pro-apoptotic caspases. Most known IAP
      inhibitors are selective for the BIR3 domain and bind to cIAP1 and cIAP2 as well
      as XIAP. Pathways activated upon cIAP binding contribute to the function of these
      compounds. Inhibitors selective for XIAP should exert pro-apoptotic effects
      through competition with the terminal caspases. This paper details our synthetic
      explorations of a novel XIAP BIR2-selective benzazepinone screening hit with a
      focus on increasing BIR2 potency and overcoming high in vivo clearance. These
      efforts led to the discovery of benzoxazepinone 40, a potent BIR2-selective
      inhibitor with good in vivo pharmacokinetic properties which potentiates
      apoptotic signaling in a manner mechanistically distinct from that of known pan
      IAP inhibitors.

PMID- 24083783
TI  - Effects of a multifaceted intervention on cardiovascular risk factors in high
      risk hypertensive patients: the ESCAPE trial, a pragmatic cluster randomized
      trial in general practice.
AB  - BACKGROUND: Several observational studies on hypertensive patients have shown a
      gap between therapeutic targets recommended in guidelines and those achieved in
      daily practice. The ESCAPE trial aimed to determine whether a multifaceted
      intervention focused on general practitioners (GPs), could increase significantly
      the proportion of hypertensive patients at high risk in primary prevention who
      achieved all their recommended therapeutic targets. METHODS: A pragmatic, cluster
      randomized trial involving 257 GPs randomized by region. The GPs in the
      intervention group had a one-day training session and were given an electronic
      blood pressure measurement device and a short recommendation leaflet. Along with
      usual follow-up, they focused one consultation on hypertension and other
      cardiovascular risk factors every six months for two years. They also received
      feedback at baseline and at one year on their patients' clinical and biological
      parameters. Main outcome measures were change in the proportion of patients
      achieving all their therapeutic targets and each individual therapeutic target at
      two years, and quality of life. RESULTS: 1,832 high-risk hypertensive patients
      were included. After two years, the proportion of patients achieving all their
      therapeutic targets increased significantly in both groups, but significantly
      more in the intervention group: OR (odds-ratio) 1.89, (95% confidence interval
      (CI) 1.09 to 3.27, P = 0.02). Significantly more patients achieved their blood
      pressure targets in the intervention group than in the usual care group: OR 2.03
      (95% CI 1.44 to 2.88, P < 0.0001). Systolic and diastolic blood pressures
      decreased significantly more in the intervention group than in the usual care
      group, by 4.8 mmHg and 1.9 mmHg, respectively (P < 0.0001 for both). There were
      no significant difference changes in physical and mental quality of life between
      groups. CONCLUSION: An easy-to-perform, multifaceted intervention targeting only
      GPs increased significantly the proportion of high-risk hypertensive patients in
      primary prevention achieving their recommended therapeutic targets. TRIAL
      REGISTRATION: This trial was registered with ClinicalTrials.gov, number
      NCT00348855.

PMID- 24083784
TI  - Editorial comment on de la Rosette et al.

PMID- 24083785
TI  - Experience with pneumococcal polysaccharide conjugate vaccine (conjugated to
      CRM197 carrier protein) in children and adults.
AB  - Streptococcus pneumoniae-related infections are a major cause of morbidity and
      mortality in people of all ages worldwide. Pneumococcal vaccine development
      started in 1911 with a whole cell vaccine and more recently multivalent plain
      polysaccharide and polysaccharide conjugate vaccines have been developed. The
      recent vaccines rely on capsular polysaccharide antigens to induce serotype
      specific immune responses. We summarize here the presentations on pneumococcal
      polysaccharide conjugate vaccine (conjugated to CRM197 carrier protein) given
      during the integrated symposium organized and funded by Pfizer International
      Operations during the 22nd European Congress of Clinical Microbiology and
      Infectious Diseases (ECCMID) 31 March to 3 April 2012, London, UK. A dramatic
      reduction in the incidence of invasive pneumococcal diseases (IPD) due to vaccine
      serotypes (VST-IPD) has been reported since the introduction of a hepta-valent
      pneumococcal conjugate vaccine (PCV7). An indirect (herd) effect has been
      demonstrated to be associated with PCV7 infant vaccination programmes, with many
      studies reporting reductions in VST-IPD in populations that are not eligible for
      PCV7 vaccination. Since 2010, a 13-valent pneumococcal conjugate vaccine (PCV13)
      has been introduced into national immunization programmes and results from early
      surveillance suggest that this vaccine also has an impact on the serotypes unique
      to PCV13, as well as continuing to protect against the PCV7 serotypes. Data from
      a passive surveillance system in Europe in 2009, for instance, showed that the
      highest incidence of IPD remains in those aged >65 years and in children <5
      years. PCV13 has now been licensed for vaccination of adults >50 years based on
      safety and immunogenicity data; an efficacy trial is being conducted. Regardless
      of previous pneumococcal vaccination status, if the use of 23-valent
      polysaccharide is considered appropriate, it is recommended to give PCV13 first.
      Novel immunization strategies remain the only practical means to reduce
      significantly the remaining global mortality and morbidity due to S. pneumoniae
      in adults.

PMID- 24083786
TI  - Medicinal chemistry from fungi and back: discovery of novel anti-fungal drugs and
      mycotherapy of cancer and other diseases with fungal metabolites.

PMID- 24083787
TI  - The role of essential oils and the biological detoxification in the prevention of
      aflatoxin borne diseases.
AB  - Fungi are an important group of microorganisms. They are studied due to their
      significant impact on the environment, industry and human health. In relation to
      biological aspects, biogeochemical cycling of elements, the world of nature would
      not be possible without the contribution of fungi as the primary decomposers of
      organic material. On the other hand, food decay by the fungi spoilage causes
      considerable economic losses and constitutes a health risk for consumers due to
      the potential of fungi to produce mycotoxins. Mycotoxins are chemically diverse
      secondary metabolites that can be harmful both to animal and human health.
      Aflatoxins, a widely studied group of toxins among mycotoxins, are mainly
      biosynthesized by Aspergillus flavus and Aspergillus parasiticus. Therefore, the
      control of fungi and the production of aflatoxins, especially the most toxic
      aflatoxins B1 and G1, is essential and decisive. Over the last few decades,
      numerous studies have demonstrated that plants, especially their essential oils,
      contain diverse bioactive components that can protect crops from becoming
      contaminated by different mold species, Aspergillus in particular, with an
      emphasis on A. flavus and A. parasiticus; as well as that, they can prevent the
      contamination of food produce during the processing and storage and prevent the
      production of aflatoxins. Plant essential oils are expected to be more
      advantageous than synthetic compounds because of their relatively safe status,
      easy decomposition, environmentally friendly and non-phytotoxic properties. This
      paper also presents the recent research in biological control of aflatoxin
      contamination. 

PMID- 24083789
TI  - New and highly potent antitumor natural products from marine-derived fungi:
      covering the period from 2003 to 2012.
AB  - This review covers the 2003-2012 literature data published for antitumor natural
      products from marine-derived fungi. The focus is on new and highly potent
      cytotoxic compounds, together with details related to the relevant fungal
      species. It describes 22 promising bioactives, originating mainly from symbiotic
      fungi. The chemical structures of all highlighted organic molecules are briefly
      discussed. 

PMID- 24083788
TI  - Mycotherapy of cancer: an update on cytotoxic and antitumor activities of
      mushrooms, bioactive principles and molecular mechanisms of their action.
AB  - Mycotherapy is defined as the study of the use of extracts and compounds obtained
      from mushrooms as medicines or health-promoting agents. The present review
      updates the recent findings on anticancer/antitumor agents derived from mushroom
      extracts and their metabolites. The increasing number of studies in the past few
      years revealed mushroom extracts as potent antitumor agents. Also, numerous
      studies were conducted on bioactive compounds isolated from mushrooms reporting
      the heteropolysaccharides, beta-glucans, alpha-glucans, proteins, complexes of
      polysaccharides with proteins, fatty acids, nucleoside antagonists, terpenoids,
      sesquiterpenes, lanostanoids, sterols and phenolic acids as promising antitumor
      agents. Also, molecular mechanisms of cytotoxicity against different cancer cell
      lines are discussed in this review. Findings with Antrodia camphorata and
      Ganoderma lucidium extracts and isolated compounds are presented, as being the
      most deeply studied previously. 

PMID- 24083790
TI  - Therapeutic properties of mushrooms in managing adverse effects in the metabolic
      syndrome.
AB  - Metabolic syndrome (MS) is a modern medical condition characterized by central
      obesity, hyperglycaemia, hypercholesterolemia and hypertension. The beneficial
      effects of mushrooms in lowering the symptoms of MS were known from both
      traditional and conventional medicine. Edible mushrooms, their extracts,
      polysaccharide fractions and isolated compounds possessed hypoglycaemic,
      cholesterol and triglyceride lowering ability, hypotensive effects, as well as
      weight managing activity by influencing satiety. The most active compounds are
      polysaccharides, called beta-glucans, as well as lectines and small compounds
      such as eritadenin, triterpenes, sterols and phenolic compounds. 

PMID- 24083791
TI  - Synthesis and biological evaluation of potent antifungal agents.
AB  - The last two decades are characterized by major increases in the incidence of
      systemic fungal infections caused by the yeast Candida albicans, particularly in
      immunocompromised patients. On the other hand it was observed the increased
      number of pathogenic microorganisms with multiple resistance to drugs. Also there
      is a big variety of drugs for the treatment of candidiasis, only two drugs are
      used for the treatment of infections from Aspergillus fumigatus. Taking into
      account that the long term therapy with azoles results in resistance a critical
      need exists for new antifungal agents with fewer side effecgts to treat these
      life-threatening fungal infections. This review will cover the advances in
      research of biological activity of different compounds from different chemical
      classes with focus on their antifungal properties. 

PMID- 24083792
TI  - Recent advances in the use of cyclodextrins in antifungal formulations.
AB  - Cyclodextrins are usually used in antifungal formulations as auxiliary substances
      to improve solubility, stability, or other physicochemical properties of the
      active compound. Nevertheless, more and more research and practical use results
      indicate that cyclodextrins might also act as active compounds in pharmaceutical
      formulations. The biological effects of cyclodextrins, important for their use
      within antimycotic formulations, can be divided into: effects based on the
      ability of cyclodextrins to form inclusion complexes with endogenous substances
      (membrane lipids, cellular cholesterol), effects based on formation of inclusion
      complexes with component parts of fungi cells, and effects based on the chemical
      nature of cyclodextrins and their derivatives. This review will cover the
      advances in research of biological activity of cyclodextrins with focus on their
      properties responsible for their synergistic effect with antimycotic compounds. 

PMID- 24083793
TI  - Antioxidant protective effects of mushroom metabolites.
AB  - Global industrialization and agricultural development are related to the release
      of various pollutants into the environment including huge amounts of free
      radicals, which are associated with the occurrence of various destructive
      diseases and disorders. Due to different rates of metabolic activity and oxygen
      consumption, organisms, organs and tissues have distinct protective antioxidant
      systems and defence mechanisms. Although numerous synthetic antioxidants can
      improve defence system capacity, because of their toxic and mutagenic effects as
      well as rising awareness of a healthy lifestyle, preference is given to natural
      antioxidants. Therefore, studies of metabolites of various fungal species and
      their activity are currently increasing. Antioxidant features of numerous
      compounds isolated from mushrooms, such as phenolic compounds, vitamins,
      polysaccharides, peptides, proteins, organic acids, carotenoids, alkaloids, and
      nucleotides, have been reported. Chemical composition and antioxidant potential
      of mushrooms are highly-dependent on species, habitat, phase of life cycle
      (mycelium, young or mature fruiting body), method of processing, extraction
      solvent, and extract dose. Although around only 5% of fungal species have been
      well studied and thousands more species have potential benefit for mankind,
      reports on the antioxidant potentials of fungi are already numerous and these are
      the subject of this review. 

PMID- 24083794
TI  - A review on antifungal activity of mushroom (basidiomycetes) extracts and
      isolated compounds.
AB  - The present review reports the antifungal activity of mushroom extracts and
      isolated compounds including high (e.g. peptides and proteins) and low (e.g.
      sesquiterpenes and other terpenes, steroids, organic acids,
      acylcyclopentenediones and quinolines) molecular weight compounds. Most of the
      studies available on literature focused on screening of antifungal activity of
      mushroom extracts, rather than of isolated compounds. Data indicate that mushroom
      extracts are mainly tested against different Candida species, while mushroom
      compounds are mostly tested upon other fungi. Therefore, the potential of these
      compounds might be more useful in food industry than in clinics. Oudemansiella
      canarii and Agaricus bisporus methanolic extracts proved to be the most active
      mushroom extracts against Candida spp. Grifolin, isolated from Albatrellus
      dispansus, seemed to be the most active compound against phytopathogenic fungi.
      Further studies should be performed in order to better understand the mechanism
      of action of this and other antifungal compounds as well as safety issues. 

PMID- 24083795
TI  - Attitudes and approaches to vaginal atrophy in postmenopausal women: a focus
      group qualitative study.
AB  - OBJECTIVE: The impact of postmenopausal vaginal atrophy and women's coping
      strategies were evaluated through international focus groups. METHODS: Three-hour
      focus groups of three to five postmenopausal women who had symptoms of vaginal
      atrophy but had not sought treatment were conducted in Canada, Sweden, the United
      States, and the United Kingdom. Participants were asked about their experience
      with menopause and vaginal atrophy, including use of non-prescription treatments
      and their interactions with health-care providers. Women were classified as one
      of five personality types, based on their interaction with the world
      (individualism or belonging) and strategies for coping with stress (control or
      liberation). RESULTS: Vaginal atrophy was not recognized as a medical condition
      by focus group participants, and women had not used treatments for vaginal
      atrophy apart from non-prescription lubricants. Women who had discussed vaginal
      atrophy symptoms with their doctor felt their concerns were dismissed as a normal
      part of aging, and they did not receive counseling about treatment options such
      as low-dose estrogen therapy. Those whose coping strategy involved dominance,
      combatting, or individualism were more likely to seek treatment than those whose
      strategy involved submission, acceptance, or belonging. Women who used control to
      cope with menopausal changes were more likely to respond to information validated
      by perceived experts than were those who used a strategy of release. CONCLUSIONS:
      Women's reactions to their vaginal atrophy varied according to personality. Use
      of a personality-based approach to patient counseling may encourage patients to
      discuss vaginal atrophy with their health-care provider and seek treatment.

PMID- 24083796
TI  - Quo vadis pulmonary autograft--the ross procedure in its second decade: a single
      center experience in 645 patients.
AB  - BACKGROUND: The enthusiasm about the advantages of a viable autologous transplant
      faded with recent reports of autograft deterioration and associated reoperations
      after the Ross procedure. This report evaluates predictors for autograft failure
      and outcomes extending into the second decade after a Ross procedure. METHODS:
      From 1995 through 2012, 645 consecutive patients (mean age, 42.3 +/- 14.2 years;
      76% males) underwent a Ross operation using mainly the root replacement technique
      (98%). They were prospectively followed up with clinical and echocardiographic
      evaluations. Total follow-up was 5,349 patient-years and was 96% complete. Mean
      follow-up duration was 8.4 +/- 4.6 years (range, 0 to 17.4 years). RESULTS: Early
      mortality was 0.9% (n = 6). Cumulative survival at 15 years was 92.7% (95%
      confidence interval, 90.1% to 95.3%) and did not differ from the general German
      population (p = 0.261). Freedom from reoperation on the autograft or the
      pulmonary allograft at 12 years was 91.6% (95% confidence interval, 88.5% to
      94.9%) and 95.0% (95% confidence interval, 92.8% to 97.2%), respectively. Sixty
      five patients (10.1%) required a total of 78 valve-related reoperations after a
      Ross procedure (1.5%/patient-year) with a reoperative hospital mortality of 3.8%
      (n = 3). Forty-seven autograft reoperations were observed in 44 patients
      (0.87%/patient-year); 22 of them (47%) could be performed as a valve-sparing
      procedure. Preoperative aortic valve regurgitation and an aortic annulus of at
      least 26 mm were identified as predictors for autograft failure. CONCLUSIONS: In
      this large series, the Ross procedure resulted in excellent long-term survival
      rates with a low risk of valve-related morbidity and a considerably low rate of
      reoperations in young and middle-aged patients and should be considered as an
      important treatment option in this cohort.

PMID- 24083797
TI  - Transapical aortic valve implantation: learning curve with reduced operating time
      and radiation exposure.
AB  - BACKGROUND: The purpose of this study was to test whether, and in which terms,
      the cumulative institutional experience in the field of transapical transcatheter
      aortic valve implantation (TAVI) might impact upon operative time and radiation
      exposure. METHODS: This was a retrospective, single-center, observational cohort
      study of prospectively collected data from all 500 consecutive high-risk patients
      undergoing transapical TAVI at our institution between April 2008 and December
      2011. Differences during the study period in baseline characteristics, procedural
      and post-procedural variables, and survival were analyzed. Nonparametric
      correlation and linear regression analyses were used to identify changes in
      operative time, contrast agent use, and radiation exposure according to
      institutional cumulative experience. RESULTS: Median operating time was 90
      minutes (interquartile range 75-115 min) and fluoroscopy time was 6.7 minutes
      (4.8-10.3 min). Combined planned percutaneous coronary intervention was performed
      in 57 (11.4%) patients. There was a significant correlation between operating
      time, fluoroscopy time, and institutional experience. A 5% reduction in operating
      time (95% CI 3% to 8%, p < 0.0001) and 15% reduction in radiation exposure time
      (95% CI 12% to 18%, p < 0.0001) was reported per 100 procedures performed.
      CONCLUSIONS: After introduction and implementation of a structured training
      program for transapical TAVI, operating time and radiation exposure are contained
      and reduced over the entire observation time in 500 consecutive patients.

PMID- 24083798
TI  - Natural history of ground-glass nodules detected on the chest computed tomography
      scan after major lung resection.
AB  - BACKGROUND: Detection of ground-glass nodules (GGNs) on computed tomography (CT)
      is increasing due to advances in CT technology and the findings of the National
      Lung Screening Trial. Ground-glass nodules are detected on screening chest CTs
      and CT scans after lung resection surgery. It is important to investigate the
      natural history of GGNs as it is not yet well known, and a standardized approach
      to manage them has not been established. METHODS: We selected patients who
      presented with GGNs on chest CT taken after major lung resection. One hundred
      thirty-nine GGNs were detected in 92 patients and followed up for longer than 1
      year. Characteristics of GGN, size, presence of a solid component and
      multiplicity, and demographic data of patients such as history of smoking and
      malignant disease were analyzed to identify factors that affected GGN growth.
      RESULTS: During the follow-up period (mean 44.4 months), 23 GGNs showed a
      significant increase in size. The only predictor for the growth of GGNs was the
      presence of a solid component (p < 0.001). Pathologic diagnosis was made in 14
      patients. Of those, 10 GGNs including 7 primary lung adenocarcinomas were
      diagnosed as malignant. Three of 4 benign lesions were diagnosed as atypical
      adenomatous hyperplasia. There were no mortalities directly related to GGNs.
      CONCLUSIONS: In GGNs detected on CT scans of patients who had undergone major
      lung resection, the presence of a solid component was the only factor that could
      predict nodule growth. Although the majority of growing GGNs were adenocarcinoma,
      the clinical course seemed to be indolent.

PMID- 24083799
TI  - Injectable small intestine submucosal extracellular matrix in an acute myocardial
      infarction model.
AB  - BACKGROUND: The mechanisms involved in myocardial regeneration and cardiac
      remodeling were examined by injecting porcine-derived small intestine submucosal
      extracellular matrix (SIS-ECM), with and without circulating angiogenic cells
      (CACs), in a mouse model of acute myocardial infarction (MI). METHODS: Nine- to
      10-week-old female C57BL/6J mice had the left anterior descending (LAD) coronary
      artery ligated. Seven days after ligation, 38 randomly allocated animals received
      echocardiographically guided intramyocardial injections of phosphate buffered
      saline (PBS), CACs, SIS-ECM, or SIS-ECM + CACs. Repeated echocardiography and
      immunohistochemical analysis were performed at 28 days after ligation. RESULTS:
      Baseline postligation left ventricular ejection fraction (LVEF) was equivalent in
      all groups. Twenty-one days after treatment, ejection fraction improved in the
      SIS-ECM + CAC treatment group (by 38% +/- 2.12%) and the SIS-ECM treatment group
      (by 36% +/- 3.71%), compared with the CAC-alone and PBS treatment groups (p <
      0.1). Masson's trichrome staining showed reduced infarct size in SIS-ECM + CACs
      (34.2% +/- 3.1%) and SIS-ECM alone (34.5% +/- 4.7%) compared with CACs alone
      (47.3% +/- 6.0%) and PBS (61.9% +/- 5.5%; p < 0.002). Arteriolar density in
      periinfarct regions was enhanced in both SIS-ECM-treated groups (by >= 78% +/-
      7%; p = 0.03). More GATA4- and beta-catenin-positive cardiac cells were found in
      the myocardium of SIS-ECM-treated animals. CONCLUSIONS: Intramyocardial delivery
      of SIS-ECM 7 days after MI in a mouse model reduced infarct size and improved
      myocardial vessel density and function; when combined with CACs it helped restore
      myocardial cellularity, suggesting a potential therapeutic role for SIS-ECM in
      cardiac regeneration.

PMID- 24083800
TI  - Effect of human glutathione S-transferases on glutathione-dependent inactivation
      of cytochrome P450-dependent reactive intermediates of diclofenac.
AB  - Idiosyncratic adverse drug reactions due to the anti-inflammatory drug diclofenac
      have been proposed to be caused by the generation of reactive acyl glucuronides
      and oxidative metabolites. For the oxidative metabolism of diclofenac by
      cytochromes P450 at least five different reactive intermediates have been
      proposed previously based on structural identification of their corresponding GSH
      conjugates. In the present study, the ability of four human glutathione S
      transferases (hGSTs) to catalyze the GSH-conjugation of the different reactive
      intermediates formed by P450s was investigated. Addition of pooled human liver
      cytosol and recombinant hGSTA1-1, hGSTM1-1, and hGSTP1-1 to incubations of
      diclofenac with human liver microsomes or purified CYP102A1M11 L437N as a model
      system significantly increased total GSH-conjugation. The strongest increase of
      total GSH-conjugation was observed by adding hGSTP1-1, whereas hGSTM1-1 and
      hGSTA1-1 showed lower activity. Addition of hGSTT1-1 only showed a minor effect.
      When considering the effects of hGSTs on GSH-conjugation of the different
      quinoneimines of diclofenac, it was found that hGSTP1-1 showed the highest
      activity in GSH-conjugation of the quinoneimine derived from 5-hydroxydiclofenac
      (5-OH-DF). hGSTM1-1 showed the highest activity in inactivation of the
      quinoneimine derived from 4'-hydroxydiclofenac (4'-OH-DF). Separate incubations
      with 5-OH-DF and 4'-OH-DF as substrates confirmed these results. hGSTs also
      catalyzed GSH-conjugation of the o-iminemethide formed by oxidative
      decarboxylation of diclofenac as well as the substitution of one of the chlorine
      atoms of DF by GSH. hGSTP1-1 showed the highest activity for the formation of
      these minor GSH-conjugates. These results suggest that hGSTs may play an
      important role in the inactivation of DF quinoneimines and its minor reactive
      intermediates especially in stress conditions when tissue levels of GSH are
      decreased. 

PMID- 24083801
TI  - Science and the lay perspective: lay people's involvement in assessing tissue
      engineering.
AB  - Tissue engineering (TE) is a scientific field that will have an influence on our
      daily lives. It has the potential to revolutionize medical treatments, but it has
      also an impact on our human image and is associated with potential risks and
      ethical aspects. Among the publicly controversial issues are embryonic and
      induced pluripotent stem cells, cloning, uncertainties regarding risks and
      informed consent issues. To maintain public confidence in the science of TE, a
      good solution is public dialogues with patients and other interested lay people
      that gives the public the chance to independently evaluate TE issues and build
      their own opinion based on information from different perspectives. The article
      describes public participation projects in TE on stem cell research and gene
      therapy and presents the case study of the EU-Gene Activated Matrices for Bone
      and Cartilage Regeneration on Arthritis (GAMBA) panels, a dialogue with patient
      and citizen panels in three European countries. In the GAMBA panels, lay
      participants assessed the basic research project aimed at finding ways of healing
      osteoarthritis through a matrix composed of adult stem cells, gene vectors,
      nanoparticles, and biomaterials. The results of the dialogues in different
      countries, such as Denmark, Japan, Ireland, Switzerland, and Germany, are
      compared and the evaluation criteria for high quality dialogues are presented,
      including multiperspectivity, openness of results, a clear mandate, impartial
      facilitation of the panels, and transparency. 

PMID- 24083802
TI  - Microscale chaotic advection enables robust convective DNA replication.
AB  - The ability of chaotic advection under microscale confinement to direct chemical
      processes along accelerated kinetic pathways has been recognized for some time.
      However, practical applications have been slow to emerge because optimal results
      are often counterintuitively achieved in flows that appear to possess undesirably
      high disorder. Here we present a 3D time-resolved analysis of polymerase chain
      reaction (PCR)-mediated DNA replication across a broad ensemble of geometric
      states. The resulting parametric map reveals an unexpectedly wide operating
      regime where reaction rates remain constant over 2 orders of magnitude of the
      Rayleigh number, encompassing virtually any realistic PCR condition (temperature,
      volume, gravitational alignment), a level of robustness previously thought
      unattainable in the convective format. 

PMID- 24083803
TI  - Coming to grips with a "new" state of consciousness: the study of rapid-eye
      movement sleep in the 1960s.
AB  - The recognition of rapid-eye-movement sleep (REM) and its association with
      dreaming in 1953 by Aserinsky and Kleitman opened a new world to explore in the
      brain. Discussions at two major symposia in the early 1960s reveal that a state
      with characteristics resembling both wakefulness and sleep was overturning
      accepted views of the regulation of the two states. Participants grappled with
      the idea that cortical activation could occur during sleep. They struggled with
      picking a name that would capture the essence of REM without focusing on just one
      aspect of the state. Questioning whether REM in cats could be homologous with
      that of humans suggested an anthropocentric focus on human dreaming as the
      essence of the state. The need for biochemical studies was evident given that
      deprivation of REM caused a rebound in the amount of subsequent REM, which
      indicated that simple synaptic activity could not support this phenomenon. 

PMID- 24083805
TI  - Ni and p-Cu2O nanocubes with a small size distribution by templated
      electrodeposition and their characterization by photocurrent measurement.
AB  - A method for the reproducible formation of Ni and Cu2O nanocubes with dimensions
      of 200-500 nm and a small size distribution is introduced. For this, the well
      known templated electrodeposition technique was extended to cubic PMMA templates
      made by nanoimprint lithography. When making cubic templates in larger
      quantities, this method has the potential to become simple and cost-effective.
      This method was successfully used for the formation of Ni and p-Cu2O nanocubes as
      well as for the formation of segmented nanobars containing both phases. The
      lateral dimensions of the nanocubes exactly resembled the dimensions of the
      template, and the height could be varied by adjusting the deposition time.
      Nanocubes formed via this method can remain attached to the substrate or can be
      dispersed in solution. p-Cu2O is considered to be one of the most promising
      photocathode materials for solar water splitting. It is demonstrated that the
      activity of the p-Cu2O nanocubes for photocatalytic water splitting can be
      measured, and it was found that the nanocube morphology enhances the
      photocatalytic activity compared to thin films. 

PMID- 24083804
TI  - Rationale and design of a randomized trial on the impact of aldosterone
      antagonism on cardiac structure and function in diabetic cardiomyopathy.
AB  - Development of a cardiomyopathy in diabetes mellitus is independent of
      traditional risk factors, with no clinical trials targeting specific therapeutic
      interventions. Myocardial fibrosis is one of the key mechanisms and aldosterone
      is a key mediator of myocardial fibrosis. We propose that aldosterone antagonism
      will improve cardiac function. We aim to evaluate the efficacy of selective
      aldosterone receptor antagonism with eplerenone added to optimal medical
      treatment in improving cardiac structure and function in diabetic cardiomyopathy.
      We will randomize 130 patients with type 2 diabetes mellitus, stable metabolic
      control and impaired left ventricular (LV) systolic or diastolic function, to
      either eplerenone (target dose 50mg) or matching placebo, in addition to optimal
      medical therapy for 12 months. The primary endpoints are changes in LV systolic
      and diastolic function, measured by echocardiographic 2-dimensional speckle
      tracking strain and strain rate and tissue Doppler imaging. The secondary
      endpoints include changes in echocardiographic markers and plasma biomarkers of
      collagen turnover; left atrial dimensions and function, incidence of atrial
      fibrillation and changes in exercise capacity and dyspnea score. The present
      study will assess whether specific aldosterone antagonism with eplerenone in
      addition to standard therapy will prevent progression or reverse cardiac
      dysfunction in diabetic cardiomyopathy using sensitive, robust and quantifiable
      echocardiographic measures that allow early detection of change. The study may
      offer a new direction in the management of this condition. TRIAL REGISTRATION:
      ACTRN12610001063000.

PMID- 24083806
TI  - A framework for credentialing naturopathic physicians in academic health centers:
      Oregon Health and Science University.

PMID- 24083807
TI  - Combining in silico and biophysical methods for the development of Pseudomonas
      aeruginosa quorum sensing inhibitors: an alternative approach for structure-based
      drug design.
AB  - The present work deals with the optimization of an inhibitor of PqsD, an enzyme
      essential for Pseudomonas aeruginosa quorum sensing apparatus. Molecular docking
      studies, supported by biophysical methods (surface plasmon resonance, isothermal
      titration calorimetry, saturation transfer difference NMR), were used to
      illuminate the binding mode of the 5-aryl-ureidothiophene-2-carboxylic acids.
      Enabled to make profound predictions, structure-based optimization led to
      increased inhibitory potency. Finally a covalent inhibitor was obtained. Binding
      to the active site was confirmed by LC-ESI-MS and MALDI-TOF-MS experiments.
      Following this rational approach, potent PqsD inhibitors were efficiently
      developed within a short period of time. This example shows that a combination
      and careful application of in silico and biophysical methods represents a
      powerful complement to cocrystallography. 

PMID- 24083808
TI  - A historical perspective of immunotoxicology.
AB  - An historical perspective of immunotoxicology is presented beginning from early
      observations in which exposure to workplace environments led to unexpected immune
      mediated lung diseases to its eventual evolution as a sub-discipline in
      toxicology. As with most toxicology disciplines, immunotoxicology originated from
      concerns by scientists within industry and government as well as medical
      professionals to limit human exposure to agents that can potentially effect human
      health. The basis for these concerns originated from laboratory studies in
      experimental models and clinical observations that suggested certain industrial
      and agrochemicals, pharmaceuticals and consumer products were capable of
      inadvertently interacting with the immune system and cause adverse health
      effects. The types of immunopathologies observed and mechanisms responsible were
      found to be broad, being dependent upon the physiochemical properties of an
      agent, exposure route, and target organ/tissue, and included
      allergic/hypersensitivity responses, immune dysfunction, manifested by
      suppression or, in rare instances, stimulation, autoimmune or autoimmune-like
      diseases, and chronic inflammatory disorders.

PMID- 24083809
TI  - Yusho patients show increased serum IL-17, IL-23, IL-1beta, and TNFalpha levels
      more than 40 years after accidental polychlorinated biphenyl poisoning.
AB  - The Yusho poisoning incident, caused by rice oil contaminated with
      polychlorinated biphenyls (PCBs), polychlorinated quarterphenyls (PCQs), and
      polychlorinated dibenzofurans (PCDFs) generated by heat-denatured PCBs, occurred
      in 1968 in western Japan. Although severe symptoms are rarely observed today, the
      levels of PCBs and PCDFs in the sera of Yusho patients remain high. The aryl
      hydrocarbon receptor (AhR), which also acts as a dioxin receptor, is a
      transcriptional regulator that mediates dioxin toxicity. Recent studies show that
      dioxin mediates its immune toxic effects via AhR and that AhR activation induces
      dysregulation of interleukin (IL)-17- producing T (TH17) cells. This study
      therefore hypothesized that Yusho patients would show dysregulated TH17 cell
      mediated immune responses. To validate the hypothesis, levels of IL-17 and IL-22,
      each secreted by TH17 cells, along with IL-1beta and IL-23 were measured in serum
      samples from 40 Yusho patients and 40 age-matched controls. Levels of tumor
      necrosis factor (TNF)-alpha potentially secreted by TH17 cell-stimulated
      neutrophils and macrophages were also measured. The results indicated that serum
      IL-17 levels, as well as those of IL-1beta, IL-23, and TNFalpha, were
      significantly higher in Yusho patients than in controls. In contrast, serum IL-22
      levels were significantly lower in the Yusho patients. These results suggest that
      Yusho patients have dysregulated TH17 cell-mediated immune responses that may be
      linked to inflammation.

PMID- 24083810
TI  - Fast retrospectively triggered local pulse-wave velocity measurements in mice
      with CMR-microscopy using a radial trajectory.
AB  - BACKGROUND: The aortic pulse-wave velocity (PWV) is an important indicator of
      cardiovascular risk. In recent studies MRI methods have been developed to measure
      this parameter noninvasively in mice. Present techniques require additional
      hardware for cardiac and respiratory gating. In this work a robust self-gated
      measurement of the local PWV in mice without the need of triggering probes is
      proposed. METHODS: The local PWV of 6-months-old wild-type C57BL/6J mice (n=6)
      was measured in the abdominal aorta with a retrospectively triggered radial Phase
      Contrast (PC) MR sequence using the flow-area (QA) method. A navigator signal was
      extracted from the CMR data of highly asymmetric radial projections with short
      repetition time (TR=3 ms) and post-processed with high-pass and low-pass filters
      for retrospective cardiac and respiratory gating. The self-gating signal was used
      for a reconstruction of high-resolution Cine frames of the aortic motion. To
      assess the local PWV the volume flow Q and the cross-sectional area A of the
      aorta were determined. The results were compared with the values measured with a
      triggered Cartesian and an undersampled triggered radial PC-Cine sequence.
      RESULTS: In all examined animals a self-gating signal could be extracted and used
      for retrospective breath-gating and PC-Cine reconstruction. With the non
      triggered measurement PWV values of 2.3+/-0.2 m/s were determined. These values
      are in agreement with those measured with the triggered Cartesian (2.4+/-0.2 m/s)
      and the triggered radial (2.3+/-0.2 m/s) measurement. Due to the strong
      robustness of the radial trajectory against undersampling an acceleration of more
      than two relative to the prospectively triggered Cartesian sampling could be
      achieved with the retrospective method. CONCLUSION: With the radial flow-encoding
      sequence the extraction of a self-gating signal is feasible. The retrospective
      method enables a robust and fast measurement of the local PWV without the need of
      additional trigger hardware.

PMID- 24083811
TI  - Effects of different information brochures on women's decision-making regarding
      mammography screening: study protocol for a randomized controlled questionnaire
      study.
AB  - BACKGROUND: In order to give informed consent for mammography screening, women
      need to be told the relevant facts; however, screening information often remains
      vague because of the worry that detailed information might deter women from
      participating in recommended screening programs. Since September 2010, German
      women aged 50 to 69 invited for mammography screening have received a new,
      comprehensive information brochure that frankly discusses the potential benefit
      and harm of mammography screening. In contrast, the brochure that was in use
      before September 2010 contained little relevant information.The aim of this study
      is to compare the impact of the two different brochures on the intention of women
      to undergo mammography screening, and to broaden our understanding of the effect
      that factual information has on the women's decision-making. METHODS: This is a
      controlled questionnaire study comparing knowledge, views and hypothetical
      preferences of women aged 48-49 years after receiving the old versus the new
      information brochure. German GP's in the region of North Rhine-Westfalia will be
      asked by mail and telephone to participate in the study. Eligible women will be
      recruited via their general practitioners (GPs) and randomized to groups A ('new
      brochure') and B ('old brochure'), with an intended recruitment of 173
      participants per group. The study is powered to detect a 15% higher or lower
      intention to undergo mammography screening in women informed by the new brochure.
      DISCUSSION: This study will contribute to our understanding of the decision
      making of women invited to mammography screening. From both ethical and public
      health perspectives, it is important to know whether frank, factual information
      leads to a change in the intention of women to participate in a recommended
      breast cancer screening program. TRIAL REGISTRATION: DRKS00004271.

PMID- 24083812
TI  - Optic-guided vaginal repair of vesicovaginal fistula.
AB  - BACKGROUND AND PURPOSE: The transvaginal approach for the repair of vesicovaginal
      fistula (VVF) can sometimes be challenging, especially in fistulas located near
      the vaginal cuff. We describe a simple technique for the vaginal repair of VVF
      with the use of endoscopic optics. PATIENTS AND METHODS: Three women were
      admitted to our department with urinary incontinence after total hysterectomy.
      Assessment with a clinical examination, imaging, and cystoscopy confirmed the
      diagnosis of VVF. All patients were operated on between December 2012 and January
      2013. The operations were conducted under spinal anesthesia with the patients in
      the lithotomy position. Cystoscopy was performed and retrograde pyelography ruled
      out any ureteral damage or fistula. A 10F to 12F Foley catheter was inserted into
      the fistula. From this point, the operation proceeded with optic vision,
      mimicking laparoscopic dissection and suturing techniques using a standard 5 mm,
      30-degree optic lens, a surgical monitor, and open surgical instruments. The
      fistula was circumferentially incised and widely mobilized from the surrounding
      tissues and closed without tension in two layers. A urethral Foley catheter was
      inserted and maintained for 14 days. RESULTS: The mean operative time was 70
      (range 60-80) minutes. Estimated blood loss was minimal. All patients were
      discharged at postoperative day 1. No complications were observed. At the
      postoperative first and third month follow-up visits, all patients were voiding
      without any urinary leakage or complaints. CONCLUSIONS: The use of optics in the
      vaginal repair of VVF is a useful technique. Optic guidance facilitates surgical
      vision, dissection, and hemostasis. It is also excellent for surgeon comfort,
      ergonomics, and resident training.

PMID- 24083813
TI  - Grafting with rootstocks induces extensive transcriptional re-programming in the
      shoot apical meristem of grapevine.
AB  - BACKGROUND: Grafting is widely used in the agriculture of fruit-bearing crops;
      rootstocks are known to confer differences in scion biomass in addition to
      improving other traits of agricultural interest. However, little is known about
      the effect of rootstocks on scion gene expression. The objective of this study
      was to determine whether hetero-grafting the grapevine variety Vitis vinifera cv.
      'Cabernet Sauvignon N' with two different rootstocks alters gene expression in
      the shoot apex in comparison to the auto-grafted control. Cabernet Sauvignon was
      hetero-grafted with two commercial rootstock genotypes and auto-grafted with
      itself. Vigor was quantified by measurements of root, stem, leaf and trunk
      biomass. Gene expression profiling was done using a whole genome grapevine
      microarray; four pools of five shoot apex samples were harvested 4 months after
      grafting for each scion/rootstock combination. RESULTS: The rootstocks increased
      stem biomass or conferred increased vigor by the end of the first growth cycle.
      Globally hetero-grafting two different genotypes together triggered an increase
      in shoot apex gene expression; however no genes were differentially expressed
      between the two hetero-grafts. The functional categories related to DNA,
      chromatin structure, histones, flavonoids and leucine rich repeat containing
      receptor kinases were the most enriched in the up-regulated genes in the shoot
      apex of hetero-grafted plants. CONCLUSIONS: The choice of rootstock genotype had
      little effect on the gene expression in the shoot apex; this could suggest that
      auto- and hetero-grafting was the major factor regulating gene expression.

PMID- 24083814
TI  - Antitumor activity of an enzyme prodrug therapy targeted to the breast tumor
      vasculature.
AB  - The L-methioninase-annexin V/selenomethionine enzyme prodrug system, designed to
      target the tumor vasculature and release the methylselenol anticancer drug in the
      tumor, was tested in mice with implanted MBA-MB-231 breast tumors. This therapy
      was able to cause a reduction in the size of the tumors during the treatment
      period. It was shown that L-methioninase-annexin V was uniformly bound at the
      blood vessel surface in the tumor and also that there was a substantial cutoff of
      blood flowing through the treated tumor, consistent with the therapy's design.
      This new approach for enzyme prodrug therapy of breast cancer appears promising. 

PMID- 24083815
TI  - Frontline therapy for multiple myeloma: a concise review of the evidence based on
      randomized clinical trials.
AB  - The past decade has seen significant progress in the development of new and
      effective therapies for multiple myeloma. Stem cell transplantation and the
      introduction of novel agents, such as thalidomide, lenalidomide, and bortezomib,
      have significantly improved outcomes of myeloma patients. In the current review,
      we analyzed the available data provided by published randomized clinical trials
      for the frontline therapy of myeloma patients. We attempted to assess the
      relative contribution and impact of these new therapies in the setting of both,
      transplant eligible and transplant ineligible patients. 

PMID- 24083816
TI  - Progesterone alters global transcription profiles at environmental concentrations
      in brain and ovary of female zebrafish (Danio rerio).
AB  - Progesterone (P4) is a natural steroid hormone excreted by humans and animals.
      Noncomplete degradation in treatment plants result in levels in the ng/L range in
      surface waters. Very little is known of the effects on fish at such
      concentrations. Here we determine the global expression profile in the brain and
      ovary of female zebrafish exposed for 14 days to 3.5, 33 and 306 ng/L P4 to
      elucidate molecular effects. For validation selected transcripts were determined
      by RT-qPCR. In the brain, 54 and 255 transcripts were altered at 3.5 and 306
      ng/L, respectively. Genes related to circadian rhythm (nr1d2b, per1b), cell cycle
      and reproduction (cdc20, ccnb1) were down-regulated. In the ovary,
      transcriptional changes occurred in 200, 84 and 196 genes at 3.5, 33 and 306
      ng/L, respectively. The genes belong to different pathways including cardiac
      hypertrophy, cell cycle and its regulation. P4 slightly influenced oocyte
      maturation as revealed by histology of the ovaries. In the liver, vtg1 was down
      regulated at all concentrations and VTG protein at 306 ng/L in the blood. The
      data show molecular effects and the modes of action of P4 at environmental
      concentrations. Ultimately they may translate to adverse effects on reproduction.

PMID- 24083817
TI  - Unclassifiable small B-cell lymphoma with marked plasmacytic differentiation and
      Mott cell formation.

PMID- 24083818
TI  - Case with chronic myeloid leukemia and T315I mutation, but still in complete
      molecular response under high dose imatinib therapy.

PMID- 24083819
TI  - Surgical management of epilepsy due to cerebral cavernomas using neuronavigation
      and intraoperative MR imaging.
AB  - OBJECTIVES: Cure from seizures due to cavernomas might be surgically achieved
      dependent on both, the complete removal of the cavernoma as well as its
      surrounding hemosiderin rim. High field intraoperative MRI imaging (iopMRI) and
      neuronavigation might play a crucial role to achieve both goals. We
      retrospectively investigated the long-term results and impact of intraoperative
      1.5T MRI (iopMRI) and neuronavigation on the completeness of surgical removal of
      a cavernous malformation (CM) and its perilesional hemosiderin rim as well as
      reduction of surgical morbidity. METHODS: 26 patients (14 female, 12 male, mean
      age 39.1 years, range: 17-63 years) with CM related epilepsy were identified.
      Eighteen patients suffered from drug resistant epilepsy (69.2%). Mean duration of
      epilepsy was 11.9 years in subjects with drug resistant epilepsy (n = 18) and 0.3
      years in subjects presenting with first-time seizures (n = 8). We performed 24
      lesionectomies and two lesionectomies combined with extended temporal resections.
      Seven lesions were located extratemporally. RESULTS: Complete CM removal was
      documented by postsurgical MRI in all patients. As direct consequence of iopMRI,
      refined surgery was necessary in 11.5% of patients to achieve complete cavernoma
      removal and in another 11.5% for complete resection of additional adjacent
      epileptogenic cortex. Removal of the hemosiderin rim was confirmed by iopMRI in
      92% of patients. Two patients suffered from mild (7.7%) and one from moderate
      (3.8%) visual field deficits. Complete seizure control (Engel class 1A) was
      achieved in 80.8% of patients with a mean follow-up period of 47.7 months.
      DISCUSSION: We report excellent long-term seizure control with minimal surgical
      morbidity after complete resection of CM using our multimodal approach.

PMID- 24083820
TI  - Use of high-pressure CO2 for concentrating CrVI from electroplating wastewater by
      Mg-Al layered double hydroxide.
AB  - The desorption of Cr(VI) from Cr(VI)-adsorbed layered double hydroxide (Cr(VI)
      LDH) and the recycling of LDH adsorbent are the bottlenecks that limit the
      practical application of LDH in treating Cr(VI)-containing industrial wastewater.
      Given the strong affinity of LDH for CO2, we studied desorption and enrichment of
      Cr(VI) from Cr(VI)-LDH as well as recycling of LDH in the presence of high
      pressure CO2. Results showed that Cr(VI) solution with concentration of 500 mg/L
      could be enriched more than 20 times in each adsorption-desorption cycle. The
      regenerated LDH maintained the layer structure and the sheets as revealed by XRD
      and TEM patterns. FT-IR data showed CO2 formed HCO3(-) at high pressure. The
      transformation from CO2 to HCO3(-) followed by the anion-exchange with CrO4(2-)
      was the critical factor for Cr(VI) desorption and LDH regeneration. A pilot-scale
      experiment was carried out with 20 L Cr(VI)-containing electroplating wastewater.
      The concentration of the desorbed Cr(VI) solution could reach up to 10000 mg/L,
      which could be used in electroplating after appropriate adjustment. The main
      advantages of this method are high concentration of Cr(VI), direct reuse of
      enriched Cr(VI), and efficient regeneration of LDH adsorbent. This method showed
      promises in recycling Cr(VI) and regenerating LDH in treating industrial
      wastewater. 

PMID- 24083821
TI  - Hexadecenoic fatty acid isomers: a chemical biology approach for human plasma
      biomarker development.
AB  - Hexadecenoic fatty acids are monounsaturated lipid components, which are
      interesting targets of plasma lipidomic studies and biomarker development. The
      main positional isomers, palmitoleic (9-cis-16:1) and sapienic acids (6-cis
      16:1), have an endogenous origin from palmitic acid, the former being recognized
      as a component of adipose tissue with signaling activity, whereas the latter is
      mainly reported as a component of sebum. The trans 16:1 isomers are attributed so
      far to dietary sources of industrial and dairy fats, whereas the endogenous
      formation due to the free radical-mediated isomerization can represent an
      emerging, yet unexplored, pathway connected to cellular stress. Herein, we report
      a chemical biology approach for the development of hexadecenoic fatty acids as
      plasma biomarkers, with the first synthesis of 6-trans-16:1 and the efficient
      analytical setup with unambiguous assignment of 16:1 double bond position and
      geometry, which was applied to human commercial LDL and plasma cholesteryl
      esters. Sapienic acid was identified together with its geometrical trans isomer
      for the first time. The quantitation of hexadecenoic fatty acid isomers evidenced
      their different levels in the two lipid classes and LDL fractions, making us
      foresee interesting applications to the metabolic evaluation of fatty acid
      pathways. These findings open new perspectives for plasma lipidomics involving
      monounsaturated fatty acids, highlighting future developments for their
      evaluation in different health conditions including free radical stress. 

PMID- 24083822
TI  - First-principles density functional theory (DFT) study of gold nanorod and its
      interaction with alkanethiol ligands.
AB  - The structure and mechanical properties of gold nanorods and their interactions
      with alkenthiolate self-assembled monolayers have been determined using a novel
      first-principle density functional theory simulation approach. The multifaceted,
      1-dimensional, octagonal nanorod has alternate Au100 and Au110 surfaces. The
      structural optimization of the gold nanorods was performed with a mixed basis:
      the outermost layer of gold atoms used double-zeta plus polarization (DZP), the
      layer below used double-zeta (DZ), and the inner layers used single-zeta (SZ).
      The final structure compares favorably with simulations using DZP for all atoms.
      Phonon dispersion calculations and ab initio molecular dynamics (AIMD) were used
      to establish the dynamic and thermal stability of the system. From the AIMD
      simulations it was found that the nanorod system will undergo significant surface
      reconstruction at 300 K. In addition, when subjected to mechanical stress in the
      axial direction, the nanorod responds as an orthotropic material, with uniform
      expansion along the radial direction. The Young's moduli are 207 kbar in the
      axial direction and 631 kbar in the radial direction. The binding of
      alkanethiolates, ranging from methanethiol to pentanethiol, caused formation of
      surface point defects on the Au110 surfaces. On the Au100 surfaces, the defects
      occurred in the inner layer, creating a small surface island. These defects make
      positive and negative concavities on the gold nanorod surface, which helps the
      ligand to achieve a more stable state. The simulation results narrowed
      significant knowledge gaps on the alkanethiolate adsorption process and on their
      mutual interactions on gold nanorods. The mechanical characterization offers a
      new dimension to understand the physical chemistry of these complex
      nanoparticles. 

PMID- 24083824
TI  - Exploration of experiences in therapeutic groups for patients with severe mental
      illness: development of the Ferrara group experiences scale (FE- GES).
AB  - BACKGROUND: Group therapies are routinely provided for patients with severe
      mental illness. The factors important to the group experience of patients are
      still poorly understood and are rarely measured. To support further research and
      practice, we aimed to develop a questionnaire that captures how patients
      experience groups within a community mental health context. METHODS: An initial
      pool of 39 items was conceptually generated to assess different aspects of group
      experiences. Items were completed by 166 patients with severe mental illness
      attending group therapies in community mental health services in Italy. Patients
      with different psychiatric diagnoses who attended at least 5 group sessions were
      included. An exploratory factor analysis was used to identify different
      dimensions of group experiences and to reduce the number of items for each
      dimension. RESULTS: The resulting questionnaire has five subscales: 1) sharing of
      emotions and experiences, 2) cognitive improvement, 3) group learning, 4)
      difficulties in open expression and 5) relationships. Each subscale has 4 items.
      The scale and sub-scales have good internal consistency. CONCLUSIONS: The Ferrara
      Group Experiences Scale is conceptually derived and assesses dimensions of group
      experience that are theoretically and practically relevant. It is brief, easy to
      use and has good psychometric properties. After further validation, the scale may
      be used for research into patient experiences across different group therapy
      modalities and for evaluation in routine care.

PMID- 24083825
TI  - A human hair keratin hydrogel scaffold enhances median nerve regeneration in
      nonhuman primates: an electrophysiological and histological study.
AB  - A human hair keratin biomaterial hydrogel scaffold was evaluated as a nerve
      conduit luminal filler following median nerve transection injury in 10 Macaca
      fascicularis nonhuman primates (NHP). A 1 cm nerve gap was grafted with a
      NeuraGen(r) collagen conduit filled with either saline or keratin hydrogel and
      nerve regeneration was evaluated by electrophysiology for a period of 12 months.
      The keratin hydrogel-grafted nerves showed significant improvement in return of
      compound motor action potential (CMAP) latency and recovery of baseline nerve
      conduction velocity (NCV) compared with the saline-treated nerves. Histological
      evaluation was performed on retrieved median nerves and abductor pollicis brevis
      (APB) muscles at 12 months. Nerve histomorphometry showed a significantly larger
      nerve area in the keratin group compared with the saline group and the keratin
      APB muscles had a significantly higher myofiber density than the saline group.
      This is the first published study to show that an acellular biomaterial hydrogel
      conduit filler can be used to enhance peripheral nerve regeneration and motor
      recovery in an NHP model.

PMID- 24083827
TI  - Engineering glutathione biosynthesis of Saccharomyces cerevisiae increases
      robustness to inhibitors in pretreated lignocellulosic materials.
AB  - BACKGROUND: Production of bioethanol from lignocellulosic biomass requires the
      development of robust microorganisms that can tolerate the stressful conditions
      prevailing in lignocellulosic hydrolysates. Several inhibitors are known to
      affect the redox metabolism of cells. In this study, Saccharomyces cerevisiae was
      engineered for increased robustness by modulating the redox state through
      overexpression of GSH1, CYS3 and GLR1, three genes involved in glutathione (GSH)
      metabolism. RESULTS: Overexpression constructs were stably integrated into the
      genome of the host strains yielding five strains overexpressing GSH1, GSH1/CYS3,
      GLR1, GSH1/GLR1 and GSH1/CYS3/GLR1. Overexpression of GSH1 resulted in a 42%
      increase in the total intracellular glutathione levels compared to the wild type.
      Overexpression of GSH1/CYS3, GSH1/GLR1 and GSH1/CYS3/GLR1 all resulted in equal
      or less intracellular glutathione concentrations than overexpression of only
      GSH1, although higher than the wild type. GLR1 overexpression resulted in similar
      total glutathione levels as the wild type. Surprisingly, all recombinant strains
      had a lower [reduced glutathione]:[oxidized glutathione] ratio (ranging from 32
      67) than the wild type strain (88), suggesting a more oxidized intracellular
      environment in the engineered strains. When considering the glutathione half-cell
      redox potential (E(hc)), the difference between the strains was less pronounced.
      E(hc) for the recombinant strains ranged from -225 to -216 mV, whereas for the
      wild type it was estimated to -225 mV. To test whether the recombinant strains
      were more robust in industrially relevant conditions, they were evaluated in
      simultaneous saccharification and fermentation (SSF) of pretreated spruce. All
      strains carrying the GSH1 overexpression construct performed better than the wild
      type in terms of ethanol yield and conversion of furfural and HMF. The strain
      overexpressing GSH1/GLR1 produced 14.0 g L(-1) ethanol in 48 hours corresponding
      to an ethanol yield on hexoses of 0.17 g g(-1); while the wild type produced 8.2
      g L(-1) ethanol in 48 hours resulting in an ethanol yield on hexoses of 0.10 g g(
      1). CONCLUSIONS: In this study, we showed that engineering of the redox state by
      modulating the levels of intracellular glutathione results in increased
      robustness of S. cerevisiae in SSF of pretreated spruce.

PMID- 24083828
TI  - The default option: Why a system of presumed consent may be effective at
      increasing rates of organ donation.
AB  - In Australia, general sentiment towards organ donation is somewhat positive, but
      actual donation rates languish amongst the poorest in the western world. Even for
      registered organ donors, the Australian system mandates obtaining family consent
      for posthumous donation; making non-donation the default option. A telephone
      survey in Central Queensland, Australia (n=1289), investigated people's
      confidence regarding their decision on whether to donate organs of a deceased
      family member; whether or not they had discussed donation with their family; and
      their support for an opt-out (presumed consent) system of donation. In accord
      with our expectations, each of these factors independently predicted the wishes
      of respondents to donate their own organs. The results suggest that promoting
      organ donation as the default option may improve rates of public acceptance for
      organ donations and consequently save lives.

PMID- 24083826
TI  - Peripheral vascular dysfunction in migraine: a review.
AB  - Numerous studies have indicated an increased risk of vascular disease among
      migraineurs. Alterations in endothelial and arterial function, which predispose
      to atherosclerosis and cardiovascular diseases, have been suggested as an
      important link between migraine and vascular disease. However, the available
      evidence is inconsistent. We aimed to review and summarize the published evidence
      about the peripheral vascular dysfunction of migraineurs.We systematically
      searched in BIOSIS, the Cochrane database, Embase, Google scholar, ISI Web of
      Science, and Medline to identify articles, published up to April 2013, evaluating
      the endothelial and arterial function of migraineurs.Several lines of evidence
      for vascular dysfunction were reported in migraineurs. Findings regarding
      endothelial function are particularly controversial since studies variously
      indicated the presence of endothelial dysfunction in migraineurs, the absence of
      any difference in endothelial function between migraineurs and non-migraineurs,
      and even an enhanced endothelial function in migraineurs. Reports on arterial
      function are more consistent and suggest that functional properties of large
      arteries are altered in migraineurs.Peripheral vascular function, particularly
      arterial function, is a promising non-invasive indicator of the vascular health
      of subjects with migraine. However, further targeted research is needed to
      understand whether altered arterial function explains the increased risk of
      vascular disease among patients with migraine. 

PMID- 24083829
TI  - Impact of stone branch number on outcomes of percutaneous nephrolithotomy for
      treatment of staghorn calculi.
AB  - PURPOSE: To determine the impact of staghorn calculi branch number on outcomes of
      percutaneous nephrolithotomy (PNL). MATERIALS AND METHODS: Retrospectively, we
      evaluated 371 patients (386 renal units) who underwent PNL for staghorn calculi.
      All calculi were showed with CT three-dimensional reconstruction (3DR) imaging
      preoperatively. From 3DR images, the number of stone branching into minor renal
      calices was recorded. According to the number, patients were divided into four
      groups. Group 1: the branch number 2-4; Group 2: the branch number 5-7; Group 3:
      the branch number 8-10; Group 4: the branch number >10. The number of
      percutaneous tract, operative time, staged PNL, intraoperative blood loss,
      postoperative hospital stay, complications, main stone composition, and stone
      clearance rate were compared. RESULTS: A significantly higher ratio of multitract
      (p<0.001) and staged PNL (p<0.001), a longer operative time (p<0.001) and
      postoperative hospital stay (p=0.043), and a lower rate of stone clearance
      (p<0.05) were found in PNL for calculi with a stone branch number >=5. There was
      no statistical difference in intraoperative blood loss (p=0.101) and main stone
      composition (p=0.546). There was no statistically meaningful difference among the
      four groups based on the Clavien complication system (p=0.46). CONCLUSION: With
      the stone branch number more than five, the possibility of multitract and staged
      PNL, lower rate of stone clearance, and a longer postoperative hospital stay
      increases for staghorn calculi.

PMID- 24083830
TI  - A case report of adult lead toxicity following use of Ayurvedic herbal
      medication.
AB  - INTRODUCTION: Ayurvedic medications consist of herbs that may be intentionally
      combined with metals, such as lead, mercury, iron, and zinc. Ayurvedic
      practitioners and their patients believe that the toxic properties of the metals
      are reduced or eliminated during preparation and processing. CASE REPORT: A 69
      year old Caucasian male retired professional with a prior history of stroke
      presented for evaluation of new onset depression, fatigue, generalized weakness,
      constipation, anorexia, and weight loss. History revealed that his symptoms were
      temporally related to initiation of an Ayurvedic herbal medication. The patient
      had been previously admitted to another hospital for these symptoms and was found
      to have a severe anemia for which no etiology was found. Laboratory tests
      revealed an elevated blood lead level and a diagnosis of symptomatic lead
      toxicity was made. The patient was treated with intramuscular, intravenous, and
      oral chelation therapy to promote lead excretion. Because of complaints of
      continued poor mental function, neuropsychological tests were administered before
      and after one of the chelation treatments and showed improvement in measures of
      attention and other cognitive domains. In addition, the patient was able to
      discontinue use of antidepressant medication after chelation. DISCUSSION: A high
      index of suspicion of metal toxicity is necessary among persons with
      characteristic symptoms and signs in the absence of occupational exposure.
      Despite limited evidence for chelation in adults and in those with modest blood
      lead levels, this patient appeared to benefit from repeated chelation therapy.
      Both allopathic and alternative medicine practitioners and public health
      specialists need to be aware of the potential for contamination of and side
      effects from alternative pharmacologic and herbal therapies.

PMID- 24083831
TI  - Prognosis and ICU outcome of systemic vasculitis.
AB  - BACKGROUND: Systemic vasculitis may cause life threatening complications
      requiring admission to an intensive care unit (ICU). The aim of this study was to
      evaluate outcomes of systemic vasculitis patients admitted to the ICU and to
      identify prognosis factors. METHODS: During a ten-year period, records of 31
      adult patients with systemic vasculitis admitted to ICUs (median age: 63 y.o, sex
      ratio M/F: 21/10, SAPS II: 40) were reviewed including clinical and biological
      parameters, use of mechanical ventilation, catecholamine or/and dialysis support.
      Mortality was assessed and data were analyzed to identify predictive factors of
      outcome. RESULTS: Causes of ICU admissions were active manifestation of
      vasculitis (n = 19), septic shock (n = 8) and miscellaneous (n = 4). Sixteen
      patients (52%) died in ICU. By univariate analysis, mortality was associated with
      higher SOFA (p = 0.006) and SAPS II (p = 0.004) scores. The need for a
      catecholamine support or/and a renal replacement therapy, and the occurrence of
      an ARDS significantly worsen the prognosis. By multivariate analysis, only SAPS
      II (Odd ratio: 1.16, 95% CI [1.01; 1.33]) and BVAS scores (Odd ratio: 1.16, 95%
      CI = [1.01; 1.34]) were predictive of mortality. CONCLUSION: The mortality rate
      of severe vasculitis requiring an admission to ICU was high. High levels of SAPS
      II and BVAS scores at admission were predictive of mortality.

PMID- 24083832
TI  - Study of ultrasound stiffness imaging methods using tissue mimicking phantoms.
AB  - A pilot study was carried out to investigate the performance of ultrasound
      stiffness imaging methods namely Ultrasound Elastography Imaging (UEI) and
      Acoustic Radiation Force Impulse (ARFI) Imaging. Specifically their potential for
      characterizing different classes of solid mass lesions was analyzed using agar
      based tissue mimicking phantoms. Composite tissue mimicking phantom was prepared
      with embedded inclusions of varying stiffness from 50 kPa to 450 kPa to represent
      different stages of cancer. Acoustic properties such as sound speed, attenuation
      coefficient and acoustic impedance were characterized by pulse echo ultrasound
      test at 5 MHz frequency and they are ranged from (1564 +/- 88 to 1671 +/- 124
      m/s), (0.6915 +/- 0.123 to 0.8268 +/- 0.755 db cm(-1)MHz(-1)) and (1.61 * 10(6)
      +/- 0.127 to 1.76 * 10(6) +/- 0.045 kg m(-2)s(-1)) respectively. The elastic
      property Young's Modulus of the prepared samples was measured by conducting quasi
      static uni axial compression test under a strain rate of 0.5mm/min upto 10 %
      strain, and the values are from 50 kPa to 450 kPa for a variation of agar
      concentration from 1.7% to 6.6% by weight. The composite phantoms were imaged by
      Siemens Acuson S2000 (Siemens, Erlangen, Germany) machine using linear array
      transducer 9L4 at 8 MHz frequency; strain and displacement images were collected
      by UEI and ARFI. Shear wave velocity 4.43 +/- 0.35 m/s was also measured for high
      modulus contrast (18 dB) inclusion and X.XX m/s was found for all other
      inclusions. The images were pre processed and parameters such as Contrast
      Transfer Efficiency and lateral image profile were computed and reported. The
      results indicate that both ARFI and UEI represent the abnormalities better than
      conventional US B mode imaging whereas UEI enhances the underlying modulus
      contrast into improved strain contrast. The results are corroborated with
      literature and also with clinical patient images.

PMID- 24083833
TI  - Complexin-1 enhances the on-rate of vesicle docking via simultaneous SNARE and
      membrane interactions.
AB  - In synaptic terminals, complexin is thought to have inhibitory and activating
      roles for spontaneous "mini" release and evoked synchronized neurotransmitter
      release, respectively. We used single vesicle-vesicle microscopy imaging to study
      the effect of complexin-1 on the on-rate of docking between vesicles that mimic
      synaptic vesicles and the plasma membrane. We found that complexin-1 enhances the
      on-rate of docking of synaptic vesicle mimics containing full-length
      synaptobrevin-2 and full-length synaptotagmin-1 to plasma membrane-mimicking
      vesicles containing full-length syntaxin-1A and SNAP-25A. This effect requires
      the C-terminal domain of complexin-1, which binds to the membrane, the presence
      of PS in the membrane, and the core region of complexin-1, which binds to the
      SNARE complex. 

PMID- 24083834
TI  - Thiazolidinone-peptide hybrids as dengue virus protease inhibitors with antiviral
      activity in cell culture.
AB  - The protease of dengue virus is a promising target for antiviral drug discovery.
      We here report a new generation of peptide-hybrid inhibitors of dengue protease
      that incorporate N-substituted 5-arylidenethiazolidinone heterocycles (rhodanines
      and thiazolidinediones) as N-terminal capping groups of the peptide moiety. The
      compounds were extensively characterized with respect to inhibition of various
      proteases, inhibition mechanisms, membrane permeability, antiviral activity, and
      cytotoxicity in cell culture. A sulfur/oxygen exchange in position 2 of the
      capping heterocycle (thiazolidinedione-capped vs rhodanine-capped peptide
      hybrids) has a significant effect on these properties and activities. The most
      promising in vitro affinities were observed for thiazolidinedione-based peptide
      hybrids containing hydrophobic groups with Ki values between 1.5 and 1.8 MUM and
      competitive inhibition mechanisms. Rhodanine-capped peptide hybrids with
      hydrophobic substituents have, in correlation with their membrane permeability, a
      more pronounced antiviral activity in cell culture than the thiazolidinediones. 

PMID- 24083835
TI  - Microfluidic array with integrated oxygenation control for real-time live-cell
      imaging: effect of hypoxia on physiology of microencapsulated pancreatic islets.
AB  - In this article, we present a novel microfluidic islet array based on a
      hydrodynamic trapping principle. The lab-on-a-chip studies with live-cell
      multiparametric imaging allow understanding of physiological and
      pathophysiological changes of microencapsulated islets under hypoxic conditions.
      Using this microfluidic array and imaging analysis techniques, we demonstrate
      that hypoxia impairs the function of microencapsulated islets at the single islet
      level, showing a heterogeneous pattern reflected in intracellular calcium
      signaling, mitochondrial energetic, and redox activity. Our approach demonstrates
      an improvement over conventional hypoxia chambers that is able to rapidly
      equilibrate to true hypoxia levels through the integration of dynamic
      oxygenation. This work demonstrates the feasibility of array-based cellular
      analysis and opens up new modality to conduct informative analysis and cell-based
      screening for microencapsulated pancreatic islets. 

PMID- 24083836
TI  - Impact of cardiovascular magnetic resonance on management and clinical decision
      making in heart failure patients.
AB  - BACKGROUND: Cardiovascular magnetic resonance (CMR) can provide important
      diagnostic and prognostic information in patients with heart failure. However, in
      the current health care environment, use of a new imaging modality like CMR
      requires evidence for direct additive impact on clinical management. We sought to
      evaluate the impact of CMR on clinical management and diagnosis in patients with
      heart failure. METHODS: We prospectively studied 150 consecutive patients with
      heart failure and an ejection fraction <= 50% referred for CMR. Definitions for
      "significant clinical impact" of CMR were pre-defined and collected directly from
      medical records and/or from patients. Categories of significant clinical impact
      included: new diagnosis, medication change, hospital admission/discharge, as well
      as performance or avoidance of invasive procedures (angiography,
      revascularization, device therapy or biopsy). RESULTS: Overall, CMR had a
      significant clinical impact in 65% of patients. This included an entirely new
      diagnosis in 30% of cases and a change in management in 52%. CMR results directly
      led to angiography in 9% and to the performance of percutaneous coronary
      intervention in 7%. In a multivariable model that included clinical and imaging
      parameters, presence of late gadolinium enhancement (LGE) was the only
      independent predictor of "significant clinical impact" (OR 6.72, 95% CI 2.56
      17.60, p=0.0001). CONCLUSIONS: CMR made a significant additive clinical impact on
      management, decision-making and diagnosis in 65% of heart failure patients. This
      additive impact was seen despite universal use of prior echocardiography in this
      patient group. The presence of LGE was the best independent predictor of
      significant clinical impact following CMR.

PMID- 24083837
TI  - Impact of HIV subtype on performance of the limiting antigen-avidity enzyme
      immunoassay, the bio-rad avidity assay, and the BED capture immunoassay in Rakai,
      Uganda.
AB  - Previous studies demonstrated that individuals with subtype D HIV infection who
      had been infected for 2 or more years were frequently misclassified as assay
      positive using cross-sectional incidence assays. Samples from 510 subjects (212
      subtype A, 298 subtype D) who were infected for 2.2 to 14.5 years (median 5.4
      years) and were not virally suppressed were tested using an LAg-Avidity enzyme
      immunoassay (LAg-Avidity EIA), Bio-Rad Avidity assay, and BED capture enzyme
      immunoassay (BED-CEIA). The performance of these three assays was evaluated using
      various assay cutoff values [LAg-Avidity EIA: <1.0 OD-n and <2.0 OD-n; Bio-Rad
      Avidity assay: <40% avidity index (AI) and <80% AI; BED-CEIA: <0.8 OD-n]. The
      mean LAg-Avidity EIA result was higher for subtype A than D (4.54+/-0.95 vs.
      3.86+/-1.26, p<0.001); the mean Bio-Rad Avidity assay result was higher for
      subtype A than D (88.9%+/-12.5% vs. 75.1+/-30.5, p<0.001); and the mean BED-CEIA
      result was similar for the two subtypes (2.2+/-1.2 OD-n for subtype A, 2.2+/-1.3
      OD-n for subtype D, p<0.9). The frequency of misclassification was higher for
      individuals with subtype D infection compared to those with subtype A infection,
      using either the LAg-Avidity EIA with a cutoff of <2.0 OD-n or the Bio-Rad
      Avidity assay with cutoffs of <40% or <80% AI. No subtype-specific differences in
      assay performance were observed using the BED-CEIA. Sex and age were not
      significantly associated with misclassification by any assay. The LAg-Avidity EIA
      with a cutoff <1.0 OD-n had the lowest frequency of misclassification in this
      Ugandan population.

PMID- 24083838
TI  - Functional rotation induced by alternating protonation states in the multidrug
      transporter AcrB: all-atom molecular dynamics simulations.
AB  - The multidrug transporter AcrB actively exports a wide variety of noxious
      compounds using proton-motive force as an energy source in Gram-negative
      bacteria. AcrB adopts an asymmetric structure comprising three protomers with
      different conformations that are sequentially converted during drug export; these
      cyclic conformational changes during drug export are referred to as functional
      rotation. To investigate functional rotation driven by proton-motive force, all
      atom molecular dynamics simulations were performed. Using different protonation
      states for the titratable residues in the middle of the transmembrane domain, our
      simulations revealed the correlation between the specific protonation states and
      the side-chain configurations. Changing the protonation state for Asp408 induced
      a spontaneous structural transition, which suggests that the proton translocation
      stoichiometry may be one proton per functional rotation cycle. Furthermore, our
      simulations demonstrate that alternating the protonation states in the
      transmembrane domain induces functional rotation in the porter domain, which is
      primarily responsible for drug transport. 

PMID- 24083839
TI  - Engineered microvessels with strong alignment and high lumen density via cell
      induced fibrin gel compaction and interstitial flow.
AB  - The development of engineered microvessels with clinically relevant
      characteristics is a critical step toward the creation of engineered myocardium.
      Alignment is one such characteristic that must be achieved, as it both mimics
      native capillary beds and provides natural inlet and outlet sides for perfusion.
      A second characteristic that is currently deficient is cross-sectional lumen
      density, typically under 100 lumens/mm2; the equivalent value for human
      myocardium is 2000 lumens/mm2. Therefore, this study examined the effects of gel
      compaction and interstitial flow on microvessel alignment and lumen density.
      Strong microvessel alignment was achieved via mechanically constrained cell
      induced fibrin gel compaction following vasculogenesis, and high lumen density
      (650 lumens/mm2) was achieved by the subsequent application of low levels of
      interstitial flow. Low interstitial flow also conferred microvessel barrier
      function.

PMID- 24083843
TI  - Photoelectrochemical characterization of hydrogenated TiO2 nanotubes as
      photoanodes for sensing applications.
AB  - In this work, hydrogenated TiO2 nanotubes (H-TNTs) electrodes were successfully
      fabricated via the anodization of a titanium sheet followed by a hydrogenation
      process. Oxygen vacancies were induced in the crystalline structure of TiO2
      nanotubes (TNTs) as shallow donors that enhance the electronic conductivity of
      the TNTs. This improvement in the electronic conductivity and
      photoelectrocatalytic (PEC) performance was confirmed and evaluated by a
      photoelectrochemical characterization. Most importantly, the H-TNTs electrode was
      able to degrade potassium hydrogen phthalate (strong adsorbent) and glucose (weak
      adsorbent) indiscriminately. The corresponding photocurrents at the H-TNTs were 2
      fold greater than that of the TNTs samples for the same concentrations of the
      organic compounds. This suggests that the H-TNTs electrode can be a promising
      sensor for the PEC determination of individual organic compounds or as an
      aggregative parameter of organic compounds (e.g., chemical oxygen demand). 

PMID- 24083842
TI  - Poor functional status as a risk factor for severe Clostridium difficile
      infection in hospitalized older adults.
AB  - OBJECTIVES: To determine the role of impaired functional status as a risk factor
      for severe Clostridium difficile infection (CDI) in older adults. DESIGN:
      Prospective cohort study. SETTING: University of Michigan Health System, a 930
      bed tertiary care hospital. PARTICIPANTS: Hospitalized individuals with CDI aged
      50 and older. MEASUREMENTS: Demographic and clinical characteristics and a
      composite outcome, CDI severity score: fever (>38 degrees C), acute organ
      dysfunction, white blood cell count greater than 15,000/MUL, lack of response to
      therapy, intensive care unit admission, need for colectomy, or death from CDI.
      Preadmission functional status was assessed according to ability to perform
      activities of daily living (ADLs); participants were assigned to an ADL class
      (independent, some assistance, full assistance). Secondary outcomes included
      length of stay, 90-day mortality and readmission, and CDI recurrence. RESULTS:
      Ninety hospitalized individuals with CDI were identified (mean age 66.6 +/-
      10.2); 58 (64.4%) had severe CDI as measured according to a positive severity
      score. At baseline, 25 (27.8%) required assistance with ADLs. On univariate
      analysis, ADL class of full assistance was associated with a positive severity
      score (odds ratio (OR) = 7, 95% confidence interval (CI) = 1.83-26.79, P = .004).
      In a multivariable model including age, ADL class, congestive heart failure,
      diabetes mellitus, depression, weighted Charlson-Deyo comorbidity score,
      immunosuppression, prior CDI, and proton pump inhibitor use, an ADL class of full
      assistance retained its association with a positive severity score (OR = 8.1, 95%
      CI = 1.24-52.95, P = .03). ADL class was not associated with secondary outcomes.
      CONCLUSION: In this cohort of hospitalized older adults, impaired functional
      status was an independent risk factor for severe CDI.

PMID- 24083844
TI  - Surface modification and characterization of polycarbonate microdevices for
      capture of circulating biomarkers, both in vitro and in vivo.
AB  - Herein, we report the fabrication, characterization, and testing of a polymer
      microprojection array, for the direct and selective capture of circulating
      biomarkers from the skin of live mice. First, we modified polycarbonate wafers
      using an electrophilic aromatic substitution reaction with nitric acid to insert
      aromatic nitro-groups into the benzene rings, followed by treatment with sodium
      borohydride to reduce the nitro-groups to primary amines. Initial
      characterization by ultraviolet-visible (UV-vis) spectroscopy suggested that
      increasing acid concentration led to increased depth of material modification and
      that this was associated with decreased surface hardness and slight changes in
      surface roughness. Chemical analysis with X-ray photoelectron spectroscopy (XPS)
      and attenuated total reflectance fourier transform infrared (ATR-FT-IR)
      spectroscopy showed nitrogen species present at the surface for all acid
      concentrations used, but subsurface nitrogen species were only observed at acid
      concentrations >35%. The nitrogen species were identified as a mixture of nitro,
      imine, and amine groups, and following reduction, there was sufficient amounts of
      primary amine groups for covalent attachment of a polyethylene glycol antifouling
      layer and protein capture probes, as determined by colorimetric and radiometric
      assays. Finally, the modification scheme was applied to polycarbonate
      microprojection arrays, and we show that these devices achieve flank skin
      penetration depths and biomarker yields comparable with our previously reported
      gold-coated silicon arrays, with very low nonspecific binding even in 10% mouse
      serum (in vitro) or directly in mouse skin (in vivo). This study is the first
      demonstration showing the potential utility of polymer microprojections in
      immunodiagnostics applications. 

PMID- 24083845
TI  - Camel Streptococcus agalactiae populations are associated with specific disease
      complexes and acquired the tetracycline resistance gene tetM via a Tn916-like
      element.
AB  - Camels are the most valuable livestock species in the Horn of Africa and play a
      pivotal role in the nutritional sustainability for millions of people. Their
      health status is therefore of utmost importance for the people living in this
      region. Streptococcus agalactiae, a Group B Streptococcus (GBS), is an important
      camel pathogen. Here we present the first epidemiological study based on genetic
      and phenotypic data from African camel derived GBS. Ninety-two GBS were
      characterized using multilocus sequence typing (MLST), capsular polysaccharide
      typing and in vitro antimicrobial susceptibility testing. We analysed the GBS
      using Bayesian linkage, phylogenetic and minimum spanning tree analyses and
      compared them with human GBS from East Africa in order to investigate the level
      of genetic exchange between GBS populations in the region. Camel GBS sequence
      types (STs) were distinct from other STs reported so far. We mapped specific STs
      and capsular types to major disease complexes caused by GBS. Widespread
      resistance (34%) to tetracycline was associated with acquisition of the tetM gene
      that is carried on a Tn916-like element, and observed primarily among GBS
      isolated from mastitis. The presence of tetM within different MLST clades
      suggests acquisition on multiple occasions. Wound infections and mastitis in
      camels associated with GBS are widespread and should ideally be treated with
      antimicrobials other than tetracycline in East Africa.

PMID- 24083846
TI  - The effect of simvastatin and erythropoietin on renal fibrosis in rats with
      unilateral ureteral obstruction.
AB  - Prevention of fibrosis is a very important therapeutic strategy in the treatment
      of obstructive nephropathy (ON). The aim of this study is to show and compare the
      actions of Simvastatin (Simv) and Erythropoietin (Epo) in renal expression of
      nuclear factor kappa B (NFkappaB), transforming growth factor-beta (TGF-beta),
      basic fibroblast growth factor (bFGF), platelet-derived growth factor B (PDGF-B),
      fibronectin and development of interstitial fibrosis in rats with unilateral
      ureteral obstruction (UUO). A total of 48 Sprague-Dawley rats were allocated to 4
      groups of sham, Epo, Simv and control. Unilateral ureteral ligation was performed
      on all rats except the Sham group. For interstitial fibrosis Masson's trichrome
      stain and for the expression of TGF-beta, PDGF-B, bFGF, NFkappaB and fibronectin,
      immunohistochemical methods were used. In the Epo and Simv groups, expression of
      TGF-beta and fibronectin and staining with Masson's trichrome were less compared
      to the control group. In addition, fibronectin expression in the Epo group was
      less than the Simv group. Unlike the Simv group, NFkappaB and bFGF expression in
      the Epo group were less when compared to the control group. Consequently, it was
      seen that both Epo and Simv prevented fibrosis in ON. Epo was superior in this
      effect by suppressing the expressions of NFkappaB and bFGF more effectively than
      Simv. Based on this finding, Epo might be a better agent than Simv in the
      prevention of fibrosis in ON.

PMID- 24083847
TI  - gamma-Brass polyhedral core in intermetallics: the nanocluster model.
AB  - Using the TOPOS program package, 26-atom nanoclusters of the gamma-brass (Cu5Zn8)
      type (0@4@22 or 0@8@18) were found in 5918 crystal structures of cubic
      intermetallics. The nanocluster models were built for all the intermetallics
      using a recently developed algorithm implemented into TOPOS. The relations of the
      structures based on the 0@4@22 core are explored as a result of migration of
      atoms between different shells of the nanoclusters. It is shown that the 0@4@22
      nanoclusters frequently occur as building units of intermetallics of different
      composition and structure type. Regularities in chemical composition of 702 gamma
      brass-type nanoclusters were found within both the nanoclusters approach
      (multishell structure) and the nested-polyhedra model. A database containing all
      topological types of gamma-brass nanoclusters is created with which one can
      search for the corresponding atomic configuration in any intermetallics. 

PMID- 24083848
TI  - Meta-analysis of transperitoneal versus extraperitoneal robot-assisted radical
      prostatectomy for prostate cancer.
AB  - OBJECTIVE: To conduct a meta-analysis of studies that compared transperitoneal
      (TP) and extraperitoneal (EP) robot-assisted radical prostatectomy (RARP).
      MATERIALS AND METHODS: PubMed, the Cochrane Library, and EMBASE online databases
      were searched for studies released prior to June 2012. References were manually
      reviewed, and two researchers independently extracted the data. To assess the
      quality of the studies, the Scottish Intercollegiate Guidelines Network
      Methodology Checklist for case-control and cohort studies was applied. RESULTS:
      One randomized controlled trial and five case-control studies were identified
      that met the inclusion criteria. Within these studies, 530 patients underwent EP
      RARP, and 312 patients underwent TP-RARP. Operating room (OR) time for EP was
      shorter than for TP (mean difference, -25.551; 95% confidence interval [CI] 
      41.668 to -9.434; P=.002). For estimated blood loss, there was no significant
      difference between EP and TP (mean difference, -12.111; 95% CI -44.087 to 19.865;
      P=.458). There was a statistical difference in length of stay (LOS) between EP
      and TP patients (mean difference, -0.488; 95% CI -0.964 to -0.012; P=.044). There
      was no significant difference in margin positivity between EP and TP (odds
      ratio=1.023; 95% CI 0.656-1.573; P=.918). In complications including grade 2 or
      more than 2, there was also no difference between EP and TP (odds ratio=0.610;
      95% CI 0.341-1.089; P=.094). CONCLUSIONS: This meta-analysis suggests that
      perioperative parameters, including OR time and LOS, may be more favorable for EP
      RARP than for TP-RARP. However, the oncologic outcome of margin positivity did
      not demonstrate a significant difference between the EP and TP approaches.

PMID- 24083849
TI  - Hybrid surgical repair of complete tubular colonic duplication associated with
      anovestibular and anocutaneous fistulas.
AB  - Complete tubular colonic duplication is a rare and complex anomaly. We present a
      new technique consisting of anterior sagittal anorectoplasty and fenestration of
      the duplicated colon using a hybrid method, involving single-incisional
      laparoscope-assisted and endoscopic procedures, for a case of complete tubular
      colonic duplication associated with anovestibular and anocutaneous fistulas.

PMID- 24083850
TI  - Does single-port laparoscopic surgery reduce postoperative pain in women with
      benign gynecologic disease?
AB  - BACKGROUND: Reduced postoperative pain, one of the potential benefits of single
      port laparoscopic surgery (SP-LS), has clinically significant importance. The
      objectives of this study are to compare postoperative pain between SP-LS and
      conventional laparoscopic surgery (conventional-LS) and to evaluate the
      difference in postoperative pain between the SP-LS group and the conventional-LS
      group based on whether a hysterectomy was performed. SUBJECTS AND METHODS: We
      performed a prospective case-control study among women who underwent SP-LS
      (n=116) and conventional-LS (n=283) for benign gynecologic disease. We evaluated
      postoperative pain with a visual analog scale for pain score and the requirement
      for additional analgesics at 2, 4, 6, 12, 24, 48, and 72 hours after surgery.
      RESULTS: The pain score was significantly lower in the SP-LS group compared with
      the conventional-LS group only at 2 hours after surgery (5.70 +/- 2.33 compared
      with 6.38 +/- 2.13, P=.005). However, at all assessment times (2, 4, 6, 12, 24,
      48, and 72 hours) after surgery including a hysterectomy (n=188) and all
      assessment times except 2 hours after surgery that did not include a hysterectomy
      (n=211), there were no differences in pain score when comparing the SP-LS or
      conventional-LS groups. CONCLUSIONS: Single-port laparoscopy had no effect on
      postoperative pain except in the immediate postoperative state (2 hours following
      surgery) in women who underwent surgery that did not include a hysterectomy.

PMID- 24083851
TI  - Transoral robotic surgery experience in 44 cases.
AB  - OBJECTIVE: To report a single institution's experience with transoral robotic
      surgery (TORS) and its clinical outcomes. This was a retrospective study carried
      out at a university-affiliated teaching hospital. SUBJECTS AND METHODS: Forty
      four consecutive TORS patients with benign and malignant diseases were reviewed.
      Data on demographics, clinical parameters, and diet were collected. Surgical
      margins, local and regional recurrence, distant metastasis, 2-year disease-free
      survival rate, and 2-year survival data were reviewed for the malignant cases.
      RESULTS: Nine benign and 35 proven squamous cell carcinoma (SCCA) cases underwent
      TORS. The set-up time was 17.12 minutes (range, 10-40 minutes), and operative
      time was 53 minutes (range, 10-300 minutes). Average length of stay was 2.5 days.
      There were seven (6.8%) grade 3 surgical complications. Surgical infection rate
      was 2.3%. Benign cases were on a regular diet after TORS. Of the malignant cases,
      94% were taking peroral diet immediately after the TORS procedure. There were no
      intraoperative complications and no 30-day postoperative mortalities. The mean
      follow-up time was 25.2 months (range, 16-38 months) for malignant disease. The
      SCCA sites were in the oropharynx (30/35), larynx (2/35), and unknown primary
      with neck metastasis (3/35). Unknown primary patients were excluded in the
      surgical margin analyses. Negative margins were achieved in 91% of cases. The
      local and regional recurrence rates were 6.3% (2/32) and 3.1% (1/32),
      respectively. Two patients (6.3%) developed distant metastasis. Oropharyngeal
      SCCA cases were reviewed, of which 23 were human papillomavirus (HPV)/p16
      positive and 7 were HPV/p16 negative. The 2-year actual survival for HPV-positive
      and -negative patients was 96% (22/23) and 86% (6/7), respectively. The 2-year
      disease-free survival for HPV-positive and -negative cases was 91% (21/23) and
      71.4% (5/7), respectively. All malignant cases that underwent TORS received
      postoperative adjuvant therapy. CONCLUSIONS: TORS is a safe procedure with
      minimal complications and acceptable clinical and functional outcomes.

PMID- 24083852
TI  - Validity and timeliness of syndromic influenza surveillance during the
      autumn/winter wave of A (H1N1) influenza 2009: results of emergency medical
      dispatch, ambulance and emergency department data from three European regions.
AB  - BACKGROUND: Emergency medical service (EMS) data, particularly from the emergency
      department (ED), is a common source of information for syndromic surveillance.
      However, the entire EMS chain, consists of both out-of-hospital and in-hospital
      services. Differences in validity and timeliness across these data sources so far
      have not been studied. Neither have the differences in validity and timeliness of
      this data from different European countries. In this paper we examine the
      validity and timeliness of the entire chain of EMS data sources from three
      European regions for common syndromic influenza surveillance during the A(H1N1)
      influenza pandemic in 2009. METHODS: We gathered local, regional, or national
      information on influenza-like illness (ILI) or respiratory syndrome from an
      Austrian Emergency Medical Dispatch Service (EMD-AT), an Austrian and Belgian
      ambulance services (EP-AT, EP-BE) and from a Belgian and Spanish emergency
      department (ED-BE, ED-ES). We examined the timeliness of the EMS data in
      identifying the beginning of the autumn/winter wave of pandemic A(H1N1) influenza
      as compared to the reference data. Additionally, we determined the sensitivity
      and specificity of an aberration detection algorithm (Poisson CUSUM) in EMS data
      sources for detecting the autumn/winter wave of the A(H1N1) influenza pandemic.
      RESULTS: The ED-ES data demonstrated the most favourable validity, followed by
      the ED-BE data. The beginning of the autumn/winter wave of pandemic A(H1N1)
      influenza was identified eight days in advance in ED-BE data. The EP data
      performed stronger in data sets for large catchment areas (EP-BE) and identified
      the beginning of the autumn/winter wave almost at the same time as the reference
      data (time lag +2 days). EMD data exhibited timely identification of the
      autumn/winter wave of A(H1N1) but demonstrated weak validity measures.
      CONCLUSIONS: In this study ED data exhibited the most favourable performance in
      terms of validity and timeliness for syndromic influenza surveillance, along with
      EP data for large catchment areas. For the other data sources performance
      assessment delivered no clear results. The study shows that routinely collected
      data from EMS providers can augment and enhance public health surveillance of
      influenza by providing information during health crises in which such information
      must be both timely and readily obtainable.

PMID- 24083853
TI  - Relationship between phenol degradation efficiency and microbial community
      structure in an anaerobic SBR.
AB  - Phenol is a common wastewater contaminant from various industrial processes,
      including petrochemical refineries and chemical compounds production. Due to its
      toxicity to microbial activity, it can affect the efficiency of biological
      wastewater treatment processes. In this study, the efficiency of an Anaerobic
      Sequencing Batch Reactor (ASBR) fed with increasing phenol concentrations (from
      120 to 1200 mg L(-1)) was assessed and the relationship between phenol
      degradation capacity and the microbial community structure was evaluated. Up to a
      feeding concentration of 800 mg L(-1), the initial degradation rate steadily
      increased with phenol concentration (up to 180 mg L(-1) d(-1)) and the
      elimination capacity remained relatively constant around 27 mg phenol
      removed?gVSS(-1) d(-1). Operation at higher concentrations (1200 mg L(-1))
      resulted in a still efficient but slower process: the elimination capacity and
      the initial degradation rate decreased to, respectively, 11 mg phenol
      removed?gVSS(-1) d(-1) and 154 mg L(-1) d(-1). As revealed by Denaturing Gradient
      Gel Electrophoresis (DGGE) analysis, the increase of phenol concentration induced
      level-dependent structural modifications of the community composition which
      suggest an adaptation process. The increase of phenol concentration from 120 to
      800 mg L(-1) had little effect on the community structure, while it involved
      drastic structural changes when increasing from 800 to 1200 mg L(-1), including a
      strong community structure shift, suggesting the specialization of the community
      through the emergence and selection of most adapted phylotypes. The thresholds of
      structural and functional disturbances were similar, suggesting the correlation
      of degradation performance and community structure. The Canonical Correspondence
      Analysis (CCA) confirmed that the ASBR functional performance was essentially
      driven by specific community traits. Under the highest feeding concentration, the
      most abundant ribotype probably involved in successful phenol degradation at 1200
      mg L(-1) was affiliated to the Anaerolineaceae family.

PMID- 24083854
TI  - The adipose-derived lineage-negative cells are enriched mesenchymal stem cells
      and promote limb ischemia recovery in mice.
AB  - White adipose tissue (WAT) is a very attractive source of mesenchymal stem cells
      (MSCs) because of its availability and ease of harvest. However, the current
      method of isolating adipose tissue-derived MSCs often relies on the adhesiveness
      of the cultured stromal-vascular fraction (SVF). Unfortunately, the SVF is a
      heterogeneous cell population containing many cell types, including adipocyte
      precursor cells, endothelial cells, pericytes, multipotent MSCs, erythrocytes,
      and hematopoietic cells. Here we systematically characterized the adipose tissue
      derived lineage-negative (Lin(-)) cell population using various surface markers
      and a set of cell proliferation and differentiation assays. We demonstrate
      clearly that the Lin(-) cell population represents enriched MSCs, which were
      identified by their high expression of MSC surface markers, and that these cells
      are a robust population with a vigorous growth capability and delayed aging. This
      cell population also demonstrated a much higher capacity for differentiation into
      osteogenic, chondrogenic and adipogenic cell lineages related to MSCs than did
      the SVF. These cells promoted recovery from limb ischemia, likely via production
      of vascular endothelial growth factor, an angiogenic factor. Our study
      demonstrates that Lin(-) cells are enriched in MSCs and provides a reliable
      method for isolating purer MSCs than SVF cells from the WAT, especially for
      obtaining fresh MSCs for clinical applications. In summary, this study identified
      a new, reliable method for enrichment of WAT MSCs with regenerative repairing
      features.

PMID- 24083855
TI  - Changes in your breathing can change your brain.

PMID- 24083856
TI  - New light is shed on the enigmatic origin of the lung myofibroblast.

PMID- 24083857
TI  - Modeling respiratory syncytial virus cytopathogenesis in the human airway.

PMID- 24083858
TI  - Fluoroquinolones in the treatment of tuberculosis: which is best?

PMID- 24083859
TI  - An official American Thoracic Society/European Respiratory Society policy
      statement: disparities in respiratory health.
AB  - BACKGROUND: Health disparities, defined as a significant difference in health
      between populations, are more common for diseases of the respiratory system than
      for those of other organ systems, because of the environmental influence on
      breathing and the variation of the environment among different segments of the
      population. The lowest social groups are up to 14 times more likely to have
      respiratory diseases than are the highest. Tobacco smoke, air pollution,
      environmental exposures, and occupational hazards affect the lungs more than
      other organs, and occur disproportionately in ethnic minorities and those with
      lower socioeconomic status. Lack of access to quality health care contributes to
      disparities. METHODS: The executive committees of the American Thoracic Society
      (ATS) and European Respiratory Society (ERS) established a writing committee to
      develop a policy on health disparities. The document was reviewed, edited, and
      approved by the full executive committees and boards of directors of the
      societies. RESULTS: This document expresses a policy to address health
      disparities by promoting scientific inquiry and training, disseminating medical
      information and best practices, and monitoring and advocating for public
      respiratory health. ERS and ATS have strong international commitments, and work
      with leaders from governments, academia, and organizations to address and reduce
      avoidable health inequalities. Their training initiatives improve the function of
      health care systems and health equality. Both the ATS and ERS support all aspects
      of this document, confer regularly, and act together when possible, but the
      activities to bring about change may vary because of the differences in the
      continents where the two organizations carry out most of their activities.
      CONCLUSIONS: The ATS and ERS pledge to frame their actions to reduce respiratory
      health disparities. The vision of the ATS and ERS is that all persons attain
      better and sustained respiratory health. They call on all their members and other
      societies to join in this commitment.

PMID- 24083860
TI  - "Hole-hearted" hemoptysis.

PMID- 24083861
TI  - Reply: No indication that mineral wool causes mesothelioma.

PMID- 24083862
TI  - No indication that mineral wool causes mesothelioma.

PMID- 24083863
TI  - Statins for sepsis: distinguishing signal from the noise when designing clinical
      trials.

PMID- 24083864
TI  - Reply: Statins in sepsis.

PMID- 24083865
TI  - Paradoxical effects of positioning in patients with ARDS and preexisting
      pulmonary vasculitis or similar disorders.

PMID- 24083866
TI  - Injury-specific ex vivo treatment of the donor lung: pulmonary thrombolysis
      followed by successful lung transplantation.

PMID- 24083867
TI  - Use of technetium-99m-labeled eosinophils to detect active eosinophilic
      inflammation in humans.

PMID- 24083869
TI  - Pulmonary alveolar microlithiasis.

PMID- 24083868
TI  - Emerging human middle East respiratory syndrome coronavirus causes widespread
      infection and alveolar damage in human lungs.

PMID- 24083870
TI  - Tolerance to acute hypoxia maximally increases in case of joint effect of
      normobaric hypoxia and permissive hypercapnia in rats.
AB  - INTRODUCTION: We studied the comparative efficacy of independent and combined
      effects of normobaric hypoxia (90mmHg) and permissive hypercapnia (50mmHg) in
      increasing the tolerance of rats to acute hypobaric hypoxia. METHODS: We
      determined the time to loss of pose and life duration as a measure to assess the
      degree of tolerance of animals to hypobaric hypoxia by exposing them to an
      altitude of 11,500m (barometric=180mmHg). RESULTS: Exposure to hypercapnic
      hypoxia increased the tolerance to acute hypobaric hypoxia compared to exposure
      to normobaric hypoxia or permissive hypercapnia alone. DISCUSSION: The positive
      effects of hypercapnia and hypercapnic hypoxia occurred after one exposure, and
      increasing the number of exposures proportionally increased the tolerance to
      acute hypobaric hypoxia. The effect of permissive hypercapnia on increasing the
      tolerance to acute hypobaric hypoxia was found to be significantly greater than
      that of exposure to normobaric hypoxia. Therefore, we propose that hypercapnia is
      the dominant factor in increasing tolerance to acute hypobaric hypoxia.
      CONCLUSION: Tolerance to acute hypoxia maximally increases in case of joint
      effect of normobaric hypoxia and permissive hypercapnia.

PMID- 24083871
TI  - Dendritic cells in semen of infertile men: association with sperm quality and
      inflammatory status of the epididymis.
AB  - OBJECTIVE: To determine whether dendritic cells (DCs) are present in semen and
      whether their abundance and activation correlate with sperm quality and
      inflammatory status of the male genital tract. DESIGN: In vitro prospective
      study. SETTING: University hospital laboratory. PATIENT(S): Eighty infertile men
      and twelve control fertile men were enrolled in this study. INTERVENTION(S):
      None. MAIN OUTCOME MEASURE(S): The percentages of DCs, intracellular staining of
      cytokines, and spermatozoa DNA fragmentation index were assessed by flow
      cytometry. Seminal cytokines, neutral alpha-glucosidase, zinc, and fructose were
      measured with commercial kits. RESULT(S): A significant number of CD11c(+) HLA
      DR(+) DCs were detected in ejaculates from patients with chronic inflammation of
      genital tract, which was negatively correlated with spermatozoa motility,
      vitality, and DNA integrity. Intracellular staining of cytokines of seminal DCs
      showed enhanced ability to secrete inflammatory cytokines (interleukin [IL]
      23p19, tumor necrosis factor [TNF]-related apoptosis-inducing ligand [TRAIL], and
      TNF-alpha). Furthermore, a significant correlation was found between DCs and the
      seminal concentrations of IL-6, IL-17, IL-23, TRAIL, and neutral alpha
      glucosidase, the marker of epididymal function, in the inflammatory group but not
      in the noninflammatory and fertile groups. CONCLUSION(S): The abundance and
      activation of seminal DCs of infertile men may be closely associated with poor
      epididymal function and sperm quality.

PMID- 24083872
TI  - Laparoscopically assisted biomaterial graft for reconstruction in congenital
      atresia of vagina and cervix.
AB  - OBJECTIVE: To report successful treatment by laparoscopically assisted
      biomaterial graft for reconstruction in patients with congenital atresia of the
      uterine cervix and vagina. DESIGN: Technique and instrumentations. SETTING:
      University-based tertiary care hospital. PATIENT(S): An 18-year-old woman with
      vaginal agenesis and cervical dysgenesis and a 13-year-old woman with vaginal
      agenesis and cervical agenesis, both patients with a functional uterus.
      INTERVENTION(S): Creation of a neovagina by vaginal procedure and
      laparoscopically assisted biomaterial graft for uterovaginal anastomosis was
      performed in all patients. MAIN OUTCOME MEASURE(S): All surgical findings were
      carefully reviewed to determine the anatomic characteristics of the malformed
      cervix. Subsequent follow-up was done by referring physicians. RESULT(S):
      Uterovaginal continuity was established successfully in both patients, and all of
      the women were menstruating normally. Granulomatous polyps occurred in one
      patient, and this condition was successfully managed. At 6-month follow-up, mean
      vaginal length was 12 cm and >= 80% of neovaginal epithelium was iodine positive
      in both patients. Unimpeded menstrual flow continued after 4 years of follow-up
      in one patient and 5 years of follow-up in the other patient. CONCLUSION(S): A
      combined laparoscopic and vaginal procedure with biomaterial graft could be an
      effective alternative in selected women with atresia of cervix and vagina.

PMID- 24083873
TI  - Progesterone elevation does not compromise pregnancy rates in high responders: a
      pooled analysis of in vitro fertilization patients treated with recombinant
      follicle-stimulating hormone/gonadotropin-releasing hormone antagonist in six
      trials.
AB  - OBJECTIVE: To compare the impact of elevated P during the late follicular phase
      on the chance of pregnancy in low, normal, and high responders. DESIGN:
      Retrospective combined analysis from six clinical trials. SETTING: IVF centers.
      PATIENT(S): Women up to 39 years of age with a regular menstrual cycle and an
      indication for ovarian stimulation before IVF/intracytoplasmic sperm injection.
      INTERVENTION(S): Ovarian stimulation with recombinant (r) FSH in a GnRH
      antagonist protocol. MAIN OUTCOME MEASURE(S): Ongoing pregnancy rates (OPRs)
      assessed with the use of univariate and multivariate analyses according to serum
      P levels <= 1.5 ng/mL versus >1.5 ng/mL on the day of hCG administration and
      compared among low (1-5 oocytes), normal (6-18 oocytes), and high (>18 oocytes)
      responders. RESULT(S): A total of 157/1,866 women (8.4%; 95% confidence interval
      [CI] 7.2%-9.8%) had elevated P. Incidence of elevated P increased from 4.5% in
      low responders to 19.0% in high responders. Overall, OPRs were significantly
      lower in women with elevated P. Per started cycle, the >1.5 to <= 1.5 ng/mL
      adjusted odds ratio was 0.55 (95% CI 0.37-0.81). OPRs were not impaired in high
      responders with P elevation and were significantly higher compared with normal
      responders with P elevation. CONCLUSION(S): The incidence of elevated P increases
      with ovarian response, and elevated P at a threshold of 1.5 ng/mL is
      independently associated with a decreased chance of pregnancy in low to normal
      responders, but not in high responders, when using an rFSH/GnRH antagonist
      protocol.

PMID- 24083874
TI  - Uniparental disomy in the human blastocyst is exceedingly rare.
AB  - OBJECTIVE: To establish whether uniparental disomy (UPD) could represent an
      outcome of embryonic aneuploidy self-correction and its relevance to
      preimplantation genetic diagnosis, and to validate a method of UPD detection in
      limited quantities of cells and determine the frequency of UPD in a large sample
      size of human blastocysts. DESIGN: Retrospective observational. SETTING: Academic
      center for reproductive medicine. PATIENT(S): Couples undergoing in vitro
      fertilization (IVF) treatment whose embryos underwent trophectoderm biopsy single
      nucleotide polymorphism (SNP) array-based 24-chromosome aneuploidy screening.
      INTERVENTION(S): None. MAIN OUTCOME MEASURE(S): Rate of UPD observed in the human
      blastocyst. RESULT(S): After application of defined thresholds, 2 of 3,401
      blastocysts were found to possess isodisomy, and 0 were found to possess
      heterodisomy. The overall frequency of UPD in the human blastocyst was therefore
      0.06%. CONCLUSION(S): This validated method of detection indicates that UPD is
      extremely rare and suggests that routine screening during preimplantation genetic
      diagnosis (PGD) may not be necessary. Furthermore, chromosomal UPD is unlikely to
      explain or support the existence of embryonic self-correction.

PMID- 24083875
TI  - Obstetric and perinatal outcomes in singleton pregnancies resulting from the
      transfer of blastocyst-stage versus cleavage-stage embryos generated through in
      vitro fertilization treatment: a systematic review and meta-analysis.
AB  - OBJECTIVE: To perform a systematic review and meta-analysis of obstetric and
      perinatal complications in singleton pregnancies after the transfer of blastocyst
      stage and cleavage-stage embryos generated through IVF. DESIGN: Systematic
      review. SETTING: University hospital. PATIENT(S): Singleton pregnancies resulting
      from ET at the blastocyst stage versus those at the cleavage stage.
      INTERVENTION(S): Medline, EMBASE, Cochrane Central Register of Clinical Trials
      DARE, and CINAHL (1980-2013) were searched. Two independent reviewers extracted
      data and assessed the methodological quality of the relevant studies using CASP
      scoring. Risk ratios and risk differences were calculated in Rev Man 5.1. MAIN
      OUTCOME MEASURE(S): Very preterm birth, preterm birth, small for gestational age,
      low birth weight, very low birth weight, congenital anomalies, perinatal
      mortality, preeclampsia, and placenta previa. RESULT(S): In vitro fertilization
      pregnancies occurring as a result of ET at the blastocyst stage were associated
      with a higher relative risk (RR; 95% confidence interval [CI]) of preterm (RR
      1.27; 95% CI 1.22-1.31) and very preterm delivery (RR 1.22; 95% CI 1.10-1.35) in
      comparison with those resulting from the transfer of cleavage-stage embryos. The
      risk of growth restriction was lower in babies conceived through blastocyst
      transfer (RR 0.82; 95% CI 0.77-0.88). CONCLUSION(S): Data from observational
      studies show that ET at the blastocyst stage is associated with a higher risk of
      very preterm delivery. However, we were not able to adjust for confounders.
      Perinatal outcome data from existing randomized trials are needed to determine
      the safety of ET at the blastocyst stage compared with the cleavage stage.

PMID- 24083876
TI  - Antimullerian hormone as a measure of reproductive function in female childhood
      cancer survivors.
AB  - OBJECTIVE: To evaluate the utility of measuring antimullerian hormone (AMH) in
      childhood cancer survivors to assess ovarian reserve, pubertal status, and
      fertility potential. DESIGN: Cross-sectional study. SETTING: Academic medical
      center. PATIENT(S): Fifty-three female childhood cancer survivors, median age
      13.9 years (range: 9-25 years) recruited at least 1 year from completion of
      cancer therapy. INTERVENTION(S): None. MAIN OUTCOME MEASURE(S): Serum AMH,
      luteinizing hormone (LH), follicle-stimulating hormone (FSH), and estradiol
      measurements, pubertal/menstrual history and Tanner staging, with risk of
      gonadotoxicity classified as low or high based on chemotherapy agent and
      pelvic/abdominal radiation. RESULT(S): Thirty-one of the 53 patients (58%) in the
      cohort had diminished ovarian reserve (DOR) detected by an AMH value <1 ng/mL. We
      detected DOR by a FSH value of >12 IU/mL in 17 patients (32%). The patients
      exposed to high-risk chemotherapy or pelvic radiation were at statistically
      significantly higher risk for DOR as measured by their AMH level. The AMH level
      was also statistically significantly lower in the patients who had delayed
      puberty. CONCLUSION(S): Using the serum gonadotropins level to screen childhood
      cancer survivors for ovarian failure is a suboptimal method. The AMH value
      identified the patients at risk for delayed puberty and those who could benefit
      from fertility preservation counseling, which makes AMH perhaps the optimal
      screening tool for assessing ovarian reserve in this population.

PMID- 24083877
TI  - A time to look back: analysis of morphokinetic characteristics of human embryo
      development.
AB  - OBJECTIVE: To describe the times associated with the morphological changes that
      occur in the embryo during preimplantation development based on the largest
      sample size described with time lapse. DESIGN: Cohort study. SETTING: University
      affiliated private center. PATIENT(S): A total of 9,530 embryos from 1,806
      intracytoplasmic sperm injection (ICSI) cycles. INTERVENTION(S): None. MAIN
      OUTCOME MEASURE(S): Using a time-lapse system, embryo images were acquired for at
      least 68 hours, in some cases reaching 120-130 hours. Embryo cleavage time points
      up to 8-cell-stage (t2-t8) as well as morulae (tM) and blastocyst formation (tB)
      were registered in hours after ICSI. Additionally, duration of the cell cycle
      (cc) and synchrony (s) of the second and third cell cycles were defined. Finally,
      four subgroups of embryos were considered: the "regular divisions" group excluded
      embryos with a direct cleavage from 1 to 3 or 2 to 5 cells, and the "viable 8
      cell," the "viable blastocyst," and "implanted embryos" groups included only
      embryos viable to the 8-cell stage, blastocyst stage, or transferred and
      successfully implanted, respectively. RESULT(S): Averages of times in the general
      population were: t2 = 27.9 hours, t3 = 38.2 hours, t4 = 40.7 hours, t5 = 51.0
      hours, t6 = 54.1 hours, t7 = 56.7 hours, t8 = 59.1 hours, tM = 86.6 hours, tB =
      104.1 hours, cc2 = 10.3 hours, cc3 = 12.8 hours, s2 = 2.7 hours, and s3 = 9.9
      hours. Comparison between groups showed significant differences between regular
      divisions and viable 8 cells for t2, t3, t5, cc2, cc3, s2, and s3; between 8
      cells and blastocyst for t5, t8, tM, cc3, and s2; and between blastocyst and
      implanted embryos for t8, tM, tB, and s2. Differences in timing related to
      morphology of cleavage- and blastocyst-stage embryos were detected.
      CONCLUSION(S): A time-lapse monitoring system applied to embryology allows
      accuracy and objectivity when defining the basis of embryo development within a
      clinic. The sample size is the largest ever described that provides consistent
      information about the normal distribution of embryo developmental timings.

PMID- 24083878
TI  - Chiral 1,3,4-oxadiazol-2-ones as highly selective FAAH inhibitors.
AB  - In the present study, identification of chiral 1,3,4-oxadiazol-2-ones as potent
      and selective FAAH inhibitors has been described. The separated enantiomers
      showed clear differences in the potency and selectivity toward both FAAH and
      MAGL. Additionally, the importance of the chirality on the inhibitory activity
      and selectivity was proven by the simplification approach by removing a methyl
      group at the 3-position of the 1,3,4-oxadiazol-2-one ring. The most potent
      compound of the series, the S-enantiomer of 3-(1-(4-isobutylphenyl)ethyl)-5
      methoxy-1,3,4-oxadiazol-2(3H)-one (JZP-327A, 51), inhibited human recombinant
      FAAH (hrFAAH) in the low nanomolar range (IC50 = 11 nM), whereas its
      corresponding R-enantiomer 52 showed only moderate inhibition toward hrFAAH (IC50
      = 0.24 MUM). In contrast to hrFAAH, R-enantiomer 52 was more potent in inhibiting
      the activity of hrMAGL compared to S-enantiomer 51 (IC50 = 4.0 MUM and 16%
      inhibition at 10 MUM, respectively). The FAAH selectivity of the compound 51 over
      the supposed main off-targets, MAGL and COX, was found to be >900-fold. In
      addition, activity-based protein profiling (ABPP) indicated high selectivity over
      other serine hydrolases. Finally, the selected S-enantiomers 51, 53, and 55 were
      shown to be tight binding, slowly reversible inhibitors of the hrFAAH. 

PMID- 24083879
TI  - Ceftaroline fosamil and treatment of acute bacterial skin and skin structure
      infections: CAPTURE study experience.
AB  - The Clinical Assessment Program and TEFLARO Utilization Registry (CAPTURE) is a
      multicentre retrospective cohort study in the USA describing treatment of acute
      bacterial skin and skin structure infection (ABSSSI) with ceftaroline fosamil
      (CPT-F). Charts for review were chosen by random selection. Among 647 evaluable
      patients, 52% were obese, 46% had diabetes mellitus (DM), and 19% had peripheral
      vascular disease (PVD). Methicillin-resistant Staphylococcus aureus (MRSA) was
      recovered in 28% and methicillin-susceptible S. aureus (MSSA), 11%. Antibiotics
      were administered prior to CPT-F treatment in 80%, and concurrently in 39%.
      Clinical success overall was 85%; in patients with DM, 83%; with PVD, 76%; and in
      obese patients, 88%. Clinical success was >= 79% across all infection types; 81%
      for MRSA and 83% for MSSA; and 86% for ceftaroline monotherapy and 84% for
      concurrent therapy. These high clinical success rates support CPT-F as an
      effective treatment option for ABSSSI, including infections due to MRSA and
      patients with significant co-morbidities.

PMID- 24083880
TI  - Development of a new method for synthesis of tandem hairpin pyrrole-imidazole
      polyamide probes targeting human telomeres.
AB  - Pyrrole-imidazole (PI) polyamides bind to the minor groove of DNA in a sequence
      specific manner without causing denaturation of DNA. To visualize telomeres
      specifically, tandem hairpin PI polyamides conjugated with a fluorescent dye have
      been synthesized, but the study of telomeres using these PI polyamides has not
      been reported because of difficulties synthesizing these tandem hairpin PI
      polyamides. To synthesize tandem hairpin PI polyamides more easily, we have
      developed new PI polyamide fragments and have used them as units in Fmoc solid
      phase peptide synthesis. Using this new method, we synthesized four fluorescent
      polyamide probes for the human telomeric repeat TTAGGG, and we examined the
      binding affinities and specificities of the tandem hairpin PI polyamides, the UV
      vis absorption and fluorescence spectra of the fluorescent polyamide probes, and
      telomere staining in mouse MC12 and human HeLa cells. The polyamides synthesized
      using the new method successfully targeted to human and mouse telomeres under
      mild conditions and allow easier labeling of telomeres in the cells while
      maintaining the telomere structure. Using the fluorescent polyamides, we
      demonstrated that the telomere length at a single telomere level is related to
      the abundance of TRF1 protein, a shelterin complex component in the telomere.

PMID- 24083881
TI  - An evidence based approach to undergraduate physical assessment practicum course
      development.
AB  - Physical assessment is an important component of professional nursing practice.
      New nurse graduates experience difficulty transitioning the traditional head to
      toe physical assessment into real world nursing practice. This study was
      conducted to provide current data concerning physical assessment competencies
      utilized consistently by registered nurses. This quantitative study used a 126
      item survey mailed to 900 Registered Nurses. Participants used a Likert-type
      scale to report frequency of use for physical assessment competencies. Thirty
      seven competencies were determined to be essential components of the physical
      assessment, 18 were determined supplemental, and 71 were determined to be non
      essential. Transition of the new graduate nurse into professional practice can be
      enhanced by focusing content in physical assessment practicum courses on the
      essential competencies of physical assessment. Faculty for the university has
      analyzed data from this study to support evidence based changes to the
      undergraduate nursing program physical assessment practicum course.

PMID- 24083882
TI  - Infant feeding practices and determinants of poor breastfeeding behavior in
      Kinshasa, Democratic Republic of Congo: a descriptive study.
AB  - BACKGROUND: Although breastfeeding is almost universally accepted in the
      Democratic Republic (DR) of Congo, by the age of 2 to 3 months 65% of children
      are receiving something other than human milk. We sought to describe the infant
      feeding practices and determinants of suboptimal breastfeeding behaviors in DR
      Congo. METHODS: Survey questionnaire administered to mothers of infants aged <= 6
      months and healthcare providers who were recruited consecutively at six selected
      primary health care facilities in Kinshasa, the capital. RESULTS: All 66 mothers
      interviewed were breastfeeding. Before initiating breastfeeding, 23 gave their
      infants something other than their milk, including: sugar water (16) or water
      (2). During the twenty-four hours prior to interview, 26 (39%) infants were
      exclusively breastfed (EBF), whereas 18 (27%), 12 (18%), and 10 (15%) received
      water, tea, formula, or porridge, respectively, in addition to human milk. The
      main reasons for water supplementation included "heat" and cultural beliefs that
      water is needed for proper digestion of human milk. The main reason for formula
      supplementation was the impression that the baby was not getting enough milk; and
      for porridge supplementation, the belief that the child was old enough to start
      complementary food. Virtually all mothers reported that breastfeeding was
      discussed during antenatal clinic visit and half reported receiving help
      regarding breastfeeding from a health provider either after birth or during well
      child clinic visit. Despite a median of at least 14 years of experience in these
      facilities, healthcare workers surveyed had little to no formal training on how
      to support breastfeeding and inadequate breastfeeding-related knowledge and
      skills. The facilities lacked any written policy about breastfeeding. CONCLUSION:
      Addressing cultural beliefs, training healthcare providers adequately on
      breastfeeding support skills, and providing structured breastfeeding support
      after maternity discharge is needed to promote EBF in the DR Congo.

PMID- 24083883
TI  - A short history on pacemakers.
AB  - Artificial pacemakers have taken part or possibly driven many developments in
      cardiac science and medicine and are therefore a very important story to
      remember. This 300-year journey of discovery has been contributed to by experts
      from across the Globe. The essential foundation of knowledge such as basic
      electrophysiology and applied electrotherapy was built in the 18th century and is
      now academically and socially accepted. This line of inventions and research has
      seen: early use of meta-analyses, the initial coming together of medical or
      bioengineering and the concept of cardiac monitoring--now a mainstay in the
      hospital care of a patient. In the 21st century pacemaker developments are no
      longer solely about reducing mortality but improving morbidity. Design
      developments reduce: discomfort, additional surgeries and invasive procedures.
      New energy sources have become lighter, smaller and with a longer life span.

PMID- 24083884
TI  - Is home warfarin self-management effective? Results of the randomised Self
      Management of Anticoagulation Research Trial.
AB  - AIMS: The Warfarin Self-Management Anticoagulation Research Trial (Warfarin
      SMART) was designed to determine whether patients self-managing warfarin (PSM)
      using the CoaguChek device and a dosing algorithm developed for the trial could
      keep the INR (International Normalised Ratio) test in target range at least as
      often as patients managed by usual care by the family doctor or hospital clinic.
      METHODS AND RESULTS: 310 patients were randomly assigned to PSM or usual care.
      The PSM group was trained to perform home INR testing and warfarin dosing using a
      validated ColourChart algorithm. The primary endpoint was the proportion of times
      over 12 months that a monthly, blinded "outcome INR test", measured in a central
      laboratory, was outside the patient's target therapeutic range. The rate of out
      of-range outcome INRs was lower in PSM, and non-inferior to the usual care group
      (PSM: 36% vs. usual care: 41%, P<0.001 for non-inferiority; P=0.08 for
      superiority in closed-loop testing). The deviations from the patient's midpoint
      of target INR range (P=0.02) and number of extreme INRs (P=0.03) were
      significantly less in the PSM group than the usual-care group. There was no
      significant difference between groups in rates of bleeding or thrombotic adverse
      events. CONCLUSION: Patient self-management performed at least as well as usual
      care in maintaining the INR within the target range, without any safety concerns.
      This treatment modality for the long-term use of warfarin has the potential to
      change current local and international practice.

PMID- 24083886
TI  - Foudroyant right heart failure in a 25-year-old female struck by alternating
      current: a potential role of electric shock in the development of pulmonary
      arterial hypertension.

PMID- 24083885
TI  - Benefits and risks of additional ablation of complex fractionated atrial
      electrograms for patients with atrial fibrillation: a systematic review and meta
      analysis.
AB  - BACKGROUND: The benefits and risks of additional complex fractionated atrial
      electrograms (CFAE) ablation in patients with atrial fibrillation (AF) remain
      unclear. METHODS: Trials were identified in PubMed, Embase, Web of Science, and
      Cochrane Database, reviews, and reference lists of relevant papers. The primary
      end point was the recurrence of atrial arrhythmias after a single ablation.
      RESULTS: We meta-analyzed 11 studies (total, n=983) using random-effects model to
      compare PVI (n=478) with PVI plus CFAE ablation (PVI+CFAE) (n=505). Additional
      CFAE ablation reduced recurrence of atrial tachyarrhythmia after a single
      procedure (pooled RR 0.73; 95% CI 0.61, 0.88; P=0.0007) at >= 3-month follow-up.
      There was no evidence of heterogeneity among studies (I(2)=33%). Subgroup
      analysis demonstrated that additional CFAE ablation reduced rates of recurrence
      in nonparoxysmal AF (RR 0.68; 95% CI 0.47, 0.99; P=0.05), whereas had no effect
      on patients with paroxysmal AF (RR 0.79; 95% CI 0.59, 1.06; P=0.12). Eight
      studies reported results of post-procedure ATs. The addition of CFAE ablation
      increased the rate of post-procedure ATs (RR 1.77; 95% CI 1.02, 3.07; P=0.04).
      Additional CFAE ablation significantly increased mean procedural times
      (245.4+75.7 vs. 189.5+62.3 min, P<0.001), mean fluoroscopy (72.1+25.6 vs.
      59.5+19.3 min, P<0.001), and mean RF energy application times (75.3+38.6 vs.
      53.2+27.5 min, P<0.001). CONCLUSIONS: The adjunctive CFAE ablation could provide
      additional benefit in terms of reducing recurrence of atrial tachyarrhythmia for
      patients with nonparoxysmal AF but not for patients with paroxysmal AF after a
      single procedure with or without antiarrhythmic drugs (AADs). The main risk of
      adjunctive CFAE ablation is the increasing rate of untraceable postablation ATs.

PMID- 24083887
TI  - Effects of a psychoeducation intervention on fear and anxiety about surgery:
      randomized trial in patients undergoing coronary artery bypass grafting.
AB  - The aim of this study was to examine the impact of a brief psychoeducation group
      intervention on fear and anxiety in patients undergoing the coronary artery
      bypass grafting (CABG). Sixty consecutive patients undergoing CABG for the first
      time were recruited for a clinical trial and randomized into two groups. The
      control group received routine care. The study group received a brief
      psychoeducation group intervention combined with routine care. The
      psychoeducation session consisted of a discussion of fear and anxiety in a
      psychotherapeutic atmosphere and relaxation techniques. Fear was scored with the
      Bypass Grafting Fear Scale (BGFS) and anxiety was scored with the Spielberger
      State Inventory (STAI) Questionnaire. The BGFS and the STAI were given to the
      patients the day after hospital admission and a day before the operation to
      measure fear and anxiety. Fear scores decreased in the psychoeducation group. Of
      the 29 patients treated with psychoeducation, the mean (SD) fear score decreased
      from 4.6 (1.7) at baseline to 2.8 (1.2) before the operation (p < .001). In the
      31 patients who received routine care, there was a nonsignificant trend from 3.7
      (1.9) to 4.1 (2.1) (p > .05). The mean difference in fear score before the
      operation was significantly lower in the psychoeducation group than the routine
      care group (mean difference -1.3; 95% CI, -2.1, -.2; p < .05). There were no
      differences in anxiety scores before the operation between the psychoeducation
      and routine care groups. In patients undergoing CABG, adding psychoeducation to
      routine care had a significant positive effect on fear but not on anxiety scores.
      A larger study of psychoeducation in these patients is warranted to assess the
      efficacy of this intervention in greater detail. 

PMID- 24083888
TI  - The in vivo blood compatibility of bio-inspired small diameter vascular graft:
      effect of submicron longitudinally aligned topography.
AB  - BACKGROUND: Cardiovascular disease is the leading cause of deaths worldwide and
      the arterial reconstructive surgery remains the treatment of choice. Although
      large diameter vascular grafts have been widely used in clinical practices, there
      is an urgent need to develop a small diameter vascular graft with enhanced blood
      compatibility. Herein, we fabricated a small diameter vascular graft with
      submicron longitudinally aligned topography, which mimicked the tunica intima of
      the native arterial vessels and were tested in Sprague-Dawley (SD) rats. METHODS:
      Vascular grafts with aligned and smooth topography were prepared by
      electrospinning and were connected to the abdominal aorta of the SD rats to
      evaluate their blood compatibility. Graft patency and platelet adhesion were
      evaluated by color Doppler ultrasound and immunofluorescence respectively.
      RESULTS: We observed a significant higher patency rate (p = 0.021) and less
      thrombus formation in vascular graft with aligned topography than vascular graft
      with smooth topography. However, no significant difference between the adhesion
      rates on both vascular grafts (smooth/aligned: 0.350/00/0.120/00, p > 0.05) was
      observed. Moreover, both vascular grafts had few adherent activated platelets on
      the luminal surface. CONCLUSION: Bionic vascular graft showed enhanced blood
      compatibility due to the effect of surface topography. Therefore, it has
      considerable potential for using in clinical application.

PMID- 24083889
TI  - Effects of the decellularization method on the local stiffness of acellular
      lungs.
AB  - Lung bioengineering, a novel approach to obtain organs potentially available for
      transplantation, is based on decellularizing donor lungs and seeding natural
      scaffolds with stem cells. Various physicochemical protocols have been used to
      decellularize lungs, and their performance has been evaluated in terms of
      efficient decellularization and matrix preservation. No data are available,
      however, on the effect of different decellularization procedures on the local
      stiffness of the acellular lung. This information is important since stem cells
      directly sense the rigidity of the local site they are engrafting to during
      recellularization, and it has been shown that substrate stiffness modulates cell
      fate into different phenotypes. The aim of this study was to assess the effects
      of the decellularization procedure on the inhomogeneous local stiffness of the
      acellular lung on five different sites: alveolar septa, alveolar junctions,
      pleura, and vessels' tunica intima and tunica adventitia. Local matrix stiffness
      was measured by computing Young's modulus with atomic force microscopy after
      decellularizing the lungs of 36 healthy rats (Sprague-Dawley, male, 250-300 g)
      with four different protocols with/without perfusion through the lung circulatory
      system and using two different detergents (sodium dodecyl sulfate [SDS] and 3-[(3
      cholamidopropyl) dimethylammonio]-1-propanesulfonate [CHAPS]). The local
      stiffness of the acellular lung matrix significantly depended on the site within
      the matrix (p<0.001), ranging from ~ 15 kPa at the alveolar septum to ~ 60 kPa at
      the tunica intima. Acellular lung stiffness (p=0.003) depended significantly,
      albeit modestly, on the decellularization process. Whereas perfusion did not
      induce any significant differences in stiffness, the use of CHAPS resulted in a ~
      35% reduction compared with SDS, the influence of the detergent being more
      important in the tunica intima. In conclusion, lung matrix stiffness is
      considerably inhomogeneous, and conventional decellularization procedures do not
      result in substantially different local stiffness in the acellular lung.

PMID- 24083890
TI  - Avian synaptopodin 2 (fesselin) stabilizes myosin filaments and actomyosin in the
      presence of ATP.
AB  - Smooth muscle cells maintain filaments of actin and myosin in the presence of
      ATP, although dephosphorylated myosin filaments and actin-myosin interactions are
      unstable under those conditions in vitro. Several proteins that stabilize myosin
      filaments and that stabilize actin-myosin interactions have been identified.
      Fesselin or synaptopodin 2 appears to be another such protein. Rapid kinetic
      measurements and electron microscopy demonstrated that fesselin, isolated from
      turkey gizzard muscle, reduced the rate of dissociation of myosin filaments.
      Addition of fesselin increased both the length and thickness of myosin filaments.
      The rate of detachment of myosin, but not heavy meromyosin, from actin was also
      greatly reduced by fesselin. Data from this study suggest that fesselin
      stabilizes myosin filaments and tethers myosin to actin. These results support
      the view that one role of fesselin is to organize contractile units of myosin and
      actin. 

PMID- 24083893
TI  - Newborn length predicts early infant linear growth retardation and
      disproportionately high weight gain in a low-income population.
AB  - BACKGROUND: Stunting is prevalent by the age of 6 months in the indigenous
      population of the Western Highlands of Guatemala. AIM: The objective of this
      study was to determine the time course and predictors of linear growth failure
      and weight-for-age in early infancy. STUDY DESIGN AND SUBJECTS: One hundred and
      forty eight term newborns had measurements of length and weight in their homes,
      repeated at 3 and 6 months. Maternal measurements were also obtained. RESULTS:
      Mean +/- SD length-for-age Z-score (LAZ) declined from newborn -1.0 +/- 1.01 to 
      2.20 +/- 1.05 and -2.26 +/- 1.01 at 3 and 6 months respectively. Stunting rates
      for newborn, 3 and 6 months were 47%, 53% and 56% respectively. A multiple
      regression model (R(2) = 0.64) demonstrated that the major predictor of LAZ at 3
      months was newborn LAZ with the other predictors being newborn weight-for-age Z
      score (WAZ), gender and maternal education*maternal age interaction. Because WAZ
      remained essentially constant and LAZ declined during the same period, weight-for
      length Z-score (WLZ) increased from -0.44 to +1.28 from birth to 3 months. The
      more severe the linear growth failure, the greater WAZ was in proportion to the
      LAZ. CONCLUSION: The primary conclusion is that impaired fetal linear growth is
      the major predictor of early infant linear growth failure indicating that
      prevention needs to start with maternal interventions.

PMID- 24083894
TI  - Developmental change of amplitude-integrated electroencephalographic activity in
      preterm infants with intraventricular hemorrhage.
AB  - BACKGROUND: Amplitude-integrated electroencephalography (aEEG) allows continuous
      brain function monitoring at bedside. OBJECTIVES: This prospective cohort study
      was designed to longitudinally evaluate aEEG tracings at increased postmenstrual
      age (PMA) in preterm infants with intraventricular hemorrhage (IVH). METHODS:
      Biweekly aEEG recordings were performed on preterm infants <32 weeks gestational
      age from 24 to 36 weeks PMA. The tracings were evaluated according to a scoring
      system adapted from Burdjalov et al. RESULTS: We analyzed 496 aEEG recordings in
      105 preterm infants. The control group consisted of 42 infants with no IVH,
      whereas the IVH grade I, II, III, and IV groups consisted of 38, 8, 3, and 14
      infants, respectively. There were significant differences in the cycling and
      total maturation scores among the IVH groups at 36 weeks PMA (p = 0.010 and p =
      0.006, respectively). The IVH-IV patients maintained low scores in their cycling
      as their PMA increased, in contrast to their continuity and amplitude scores. The
      risk factors affecting the aEEG maturation scores at 36 weeks PMA in the IVH-IV
      patients included seizure events with the administration of antiepileptic drugs
      and the insertion of external ventricular drains (beta = -0.679 and beta = 
      0.418, respectively; p = 0.003). CONCLUSIONS: The low cycling scores persisted
      until 36 weeks PMA in the IVH-IV group.

PMID- 24083895
TI  - More on diphosphadithiatetrazocines and the importance of being bonded.
AB  - The cross-ring sulfur-sulfur bond for seven R'RP(NSN)2PRR' molecules 1a (R = R' =
      Me), 1b (R = R' = Ph), 1c (R = R' = Et), 1d (R = Cl, R' = CCl3), 1e (R = R'= Cl),
      1f (R = R' = F), and 1g (R = R' = H) has been scrutinized by a topology analysis
      for a bond descriptor based on the kinetic energy density, supported by a
      fragment-based bond energy analysis. Contrary to a regular disulfide bond, the
      cross-ring connection is only a secondary electron-sharing bond, about half as
      strong as a common S-S linkage. The regular disulfide bond itself is best
      described as a charge-shift bond. These analyses are based on results obtained
      from B3PW91/def2-TZVP density functional calculations. 

PMID- 24083892
TI  - Diagnosis and treatment of pulmonary hypertension in infancy.
AB  - Normal pulmonary vascular development in infancy requires maintenance of low
      pulmonary vascular resistance after birth, and is necessary for normal lung
      function and growth. The developing lung is subject to multiple genetic,
      pathological and/or environmental influences that can adversely affect lung
      adaptation, development, and growth, leading to pulmonary hypertension. New
      classifications of pulmonary hypertension are beginning to account for these
      diverse phenotypes, and or pulmonary hypertension in infants due to PPHN,
      congenital diaphragmatic hernia, and bronchopulmonary dysplasia (BPD). The most
      effective pharmacotherapeutic strategies for infants with PPHN are directed at
      selective reduction of PVR, and take advantage of a rapidly advancing
      understanding of the altered signaling pathways in the remodeled vasculature. 

PMID- 24083896
TI  - Is the perception of dysphonia severity language-dependent? A comparison of
      French and Italian voice assessments.
AB  - In this cross-language study, six Italian and six French voice experts evaluated
      perceptually the speech of 27 Italian and 40 French patients with dysphonia to
      determine if there were differences based on native language. French and Italian
      voice specialists agreed substantially in their evaluations of the overall grade
      of dysphonia and moderately concerning roughness and breathiness. No
      statistically significant effects were found related to the language of the
      speakers with the exception of breathiness, a finding that was interpreted as
      being due to different voice pathologies in the patient groups. It was concluded
      that the perception of the overall grade of dysphonia and breathiness is not
      language-dependent, whereas the significant difference in the perception of
      roughness may be related to a perception/adaption process. 

PMID- 24083898
TI  - Flexible software platform for fast-scan cyclic voltammetry data acquisition and
      analysis.
AB  - Over the last several decades, fast-scan cyclic voltammetry (FSCV) has proved to
      be a valuable analytical tool for the real-time measurement of neurotransmitter
      dynamics in vitro and in vivo. Indeed, FSCV has found application in a wide
      variety of disciplines including electrochemistry, neurobiology, and behavioral
      psychology. The maturation of FSCV as an in vivo technique led users to pose
      increasingly complex questions that require a more sophisticated experimental
      design. To accommodate recent and future advances in FSCV application, our lab
      has developed High Definition Cyclic Voltammetry (HDCV). HDCV is an
      electrochemical software suite that includes data acquisition and analysis
      programs. The data collection program delivers greater experimental flexibility
      and better user feedback through live displays. It supports experiments involving
      multiple electrodes with customized waveforms. It is compatible with transistor
      transistor logic-based systems that are used for monitoring animal behavior, and
      it enables simultaneous recording of electrochemical and electrophysiological
      data. HDCV analysis streamlines data processing with superior filtering options,
      seamlessly manages behavioral events, and integrates chemometric processing.
      Furthermore, analysis is capable of handling single files collected over extended
      periods of time, allowing the user to consider biological events on both
      subsecond and multiminute time scales. Here we describe and demonstrate the
      utility of HDCV for in vivo experiments. 

PMID- 24083899
TI  - Adsorption and biodegradation of antidiabetic pharmaceuticals in soils.
AB  - Pharmaceuticals are emerging contaminants in the natural environment. Most
      studies of the environmental fate of these chemicals focus on their behavior in
      wastewater treatment processes and in sewage sludge. Little is known about their
      behavior in soils. In this study adsorption and biodegradation of four
      antidiabetic pharmaceuticals - glimepiride, glibenclamide, gliclazide and
      metformin - were examined in three natural soils. The sorption of sulfonylurea
      derivatives was high (higher than sulfonylurea herbicides for example), whereas
      metformin showed high mobility. Desorption rates were highest for metformin.
      Sorption isotherms in two of three soils fitted best to the Freundlich model.
      Despite their high affinity to for soil surfaces, biodegradation studies revealed
      that transformation of the drugs occurred. Biodegradation results were described
      by pseudo-first order kinetics with half-life values from 5 to over 120 d (under
      aerobic conditions) and indicate that none of the tested drugs can be classified
      as quickly biodegradable. Biodegradation under anoxic conditions was much slower;
      often degrading by less than 50% during time of the experiment.

PMID- 24083897
TI  - Increase in chemokines CXCL10 and CCL2 in blood from pigs infected with high
      compared to low virulence African swine fever virus isolates.
AB  - Modulation of the expression of chemokines and chemokine receptors in whole blood
      was compared following infection of pigs with high and low virulence isolates of
      African swine fever virus. Levels of mRNAs for CCL2, CCL3L1, CCL4, CXCL10, CCR1
      and CCR5 were significantly increased in at least one time point following
      infection in two experiments and CCL5, CCR9 and CXCR4 mRNA were significantly
      increased in one of the experiments. The results showed that greatest fold
      increases in mRNAs for CXCL10 and CCL2 were observed following infection of pigs.
      CXCL10 mRNA was increased by up to 15 fold in infected compared to uninfected
      pigs. CXCL10 protein was also detected in serum from pigs infected with the high
      virulence Benin 97/1 isolate. Levels of CCL2 mRNA were increased in pigs infected
      with high virulence Benin 97/1 isolate compared to low virulence OURT88/3 isolate
      and this correlated with an increase of greater than 30 fold in levels of CCL2
      protein detected in serum from pigs infected with this isolate. An increase in
      overall chemotaxis active compounds in defibrinated plasma samples from Benin
      97/1 infected pigs was observed at 3 days post-infection (dpi) and a decrease by
      7 dpi as measured by chemotaxis assay using normal pig leucocytes in vitro.
      Increased levels of CXCL10 may either contribute to the activation of lymphocyte
      priming toward the Th1 phenotype or induction of T lymphocyte apoptosis.
      Increased levels of CCL2, a chemoattractant for macrophages, may result in
      increased recruitment of monocytes from bone marrow thus increasing the pool of
      cells susceptible to infection.

PMID- 24083900
TI  - Degradation of atenolol by UV/peroxymonosulfate: kinetics, effect of operational
      parameters and mechanism.
AB  - Photoactivation of peroxymonosulfate (PMS) with UV (254nm) irradiation was used
      to generate the SO4(-)-based advanced oxidation process, which was adopted to
      degrade atenolol (ATL) in water. The second-order reaction rate constants of ATL
      with HO and SO4(-) were determined, and the effects of operational parameters
      (dose of PMS, solution pH, HCO3(-), humic acids (HA), and N2 bubbling) were
      evaluated as well. Finally the main transformation intermediates were identified
      and possible degradation pathways were proposed. The results showed that there
      was a linear positive correlation between the degradation rate of ATL and
      specific dose of PMS (1-16M PMS/M ATL). Increasing solution pH from 3 to 9
      promoted elimination of ATL due to the pH-dependent effect of PMS
      photodecomposition, while further pH increase from 9 to 11 caused slowing down of
      degradation because of apparent conversion of HO to SO4(-). 1-8mM HCO3(-) exerted
      no more than 5.3% inhibition effect on ATL destruction, suggesting HCO3(-) was a
      weak inhibitor. Absorption (or complexation) and photosensitized oxidation
      induced by HA improved ATL degradation during the first minute of degradation
      process, whereas photon competition and radical scavenging effects became the
      leading role afterward. Bubbling with nitrogen enhanced the degradation rate due
      to the stripping of dissolved oxygen. Hydroxylation of aromatic ring, cleavage of
      ether bond, oxidation of primary and secondary amine moieties, and dimerization
      were involved in the degradation mechanism of ATL by UV/PMS. 

PMID- 24083901
TI  - Comparison of solvent extraction and solid-phase extraction for the determination
      of polychlorinated biphenyls in transformer oil.
AB  - Solid-phase extraction (SPE) of nine polychlorinated biphenyls (PCBs) from
      transformer oil samples was evaluated using octadecyl (CI8)-bonded porous silica.
      The efficiency of SPE of these PCBs was compared with those obtained by solvent
      extraction with DMSO and hexane. Average recoveries exceeding 95% for these PCBs
      were obtained via the SPE method using small cartridges containing 100mg of 40 pm
      CI8-bonded porous silica. The average recovery by solvent extraction with DMSO
      and hexane exceeded 83%. It was concluded that the recoveries and precision for
      the solvent extraction of PCBs were poorer than those for the SPE.

PMID- 24083903
TI  - Reduction of toxicity of antimicrobial compounds by degradation processes using
      activated sludge, gamma radiation, and UV.
AB  - The occurrence and persistence of pharmacologically active compounds in the
      environment has been an increasingly important issue. The objectives of this
      study were to investigate the decomposition of aqueous antimicrobial compounds
      using activated sludge, gamma-irradiation, and UV treatment, and to evaluate the
      toxicity towards green algae, Pseudokirchneriella subcapitata, before and after
      treatment. Tetracycline (TCN), lincomycin (LMC) and sulfamethazine (SMZ) were
      used as target compounds. Gamma (gamma)-irradiation showed the highest removal
      efficiency for all target compounds, while UV and activated sludge treatment
      showed compound-dependent removal efficiencies. TCN and SMZ were well degraded by
      all three treatment methods. However, LMC showed extremely low removal efficiency
      for UV and activated sludge treatments. Overall, the algal toxicity after
      degradation processes was significantly decreased, and was closely correlated to
      removal efficiency. However, in the case of gamma-irradiated TCN, UV and
      activated sludge treated LMC as well as sludge treated SMZ, the observed toxicity
      was higher than expected, which indicates the substantial generation of
      byproducts or transformed compounds of a greater toxicity in the treated sample.
      Consequently, gamma-radiation treatment could be an effective method for removal
      of recalcitrant compounds such as antibiotics. 

PMID- 24083904
TI  - Photosensitizing properties of water-extractable organic matter from soils.
AB  - Water-extractable organic matter (WEOM) was extracted using pure water from two
      black soils and from the Elliott reference soil of the International Humic
      Substances Society (IHSS). WEOMs were characterized by chemical and spectroscopic
      methods. The apparent quantum yields of singlet oxygen, triplet excited states
      and hydroxyl radicals formation upon irradiation within the wavelength range 290
      450 nm were determined using chemical probes and compared to those of standard
      Elliott humic substances. In general, the aromatic content, as measured by the
      SUVA value, was close in WEOMs and humic substances, while the E2/E3 was higher
      and the humification index lower in the former. Quantum yield values measured for
      WEOMs fell within the range of those found for basic medium extracted humic
      substances or were even higher in one case. Thus, water soluble aromatic moiety
      of the soil organic matter, especially those with low humification degree, is
      important for the photosensitizing properties. We also found that WEOMs
      sensitized the bisphenol A phototransformation with rates of the same order of
      magnitude for all the samples.

PMID- 24083902
TI  - Occurrence of drugs of abuse and benzodiazepines in river waters from the Madrid
      Region (Central Spain).
AB  - This work investigates, for the first time, the occurrence of 10 drugs of abuse,
      six metabolites, and three benzodiazepines in surface waters from the Jarama and
      Manzanares Rivers in the Madrid Region, the most densely populated area in Spain
      and one of the most densely populated in Europe. The results of this study have
      shown the presence of 14 out of the 19 compounds analyzed at concentrations
      ranging from 1.45 to 1020 ng L(-1). The most ubiquitous compounds, found in 100%
      of the samples, were the cocaine metabolite benzoylecgonine (BE), the amphetamine
      like compound ephedrine (EPH), the opioids morphine (MOR), methadone (METH), and
      the METH metabolite 2-ethylene-1,5-dimethyl-3,3-diphenylpyrrolidine (EDDP), and
      the three investigated benzodiazepines alprazolam (ALP), diazepam (DIA) and
      lorazepam (LOR). Meanwhile, the largest concentrations observed corresponded to
      EPH (up to 1020 ng L(-1)), BE (823 ng L(-1)), EDDP (151 ng L(-1)), and LOR (167
      ng L(-1)). The only not detected compounds were heroin (HER) and its metabolite 6
      acetylmorphine (6ACM), lysergic acid diethylamide (LSD) and its metabolite 2-oxo
      3-hydroxy-LSD (OH-LSD), and Delta(9)-tetrahydrocannabinol (THC). Overall, the
      levels measured are comparatively higher than those previously reported in
      Europe. Comparison of the results obtained for samples collected on different
      days (Thursday and Sunday) did not show meaningful differences between weekdays
      and weekends. The lack of (eco)toxicological data does not permit to predict or
      disregard potential adverse effects on wildlife. Risk assessment in humans would
      require further knowledge, not currently available, on exposure to these
      compounds through other routes like drinking water and/or food.

PMID- 24083905
TI  - Evaluation of the release of dioxins and PCBs during kiln-firing of ball clay.
AB  - Ball clay is known to be naturally contaminated with high levels of
      polychlorinated di-benzo-p-dioxins (PCDDs). This study evaluated the potential
      for PCDD, polychlorinated dibenzofuran (PCDF) and polychlorinated biphenyl (PCB)
      release during the kiln firing of ball clay in an art studio. Toxic equivalence
      (TEQ) were calculated using World Health Organization (WHO) 2005 toxic
      equivalence factors (TEF) and congener concentrations. Ten bags of commercial
      ball clay were found to have an average TEQ of 1,370 nanograms/kilogram (ng kg(
      1)) dry weight (dw), almost exclusively due to PCDDs (99.98% of TEQ). After
      firing, none of the 29 dioxin-like analytes was measured above the limits of
      detection (LOD) in the clay samples. Air samples were taken during firings using
      both low-flow and high-flow air samplers. Few low-flow air samples contained
      measurable levels of dioxin congeners above the LOD. The mean TEQ in the high
      volume air samples ranged from 0.07 pg m(-3) to 0.21 pg m(-3) when firing ball
      clay, and was 0.11 pg m(-3) when no clay was fired. These concentrations are
      within the range measured in typical residences and well-controlled industrial
      settings. The congener profiles in the high-flow air samples differed from the
      unfired clay; the air samples had a considerable contribution to the TEQ from
      PCDFs and PCBs. Given that the TEQs of all air samples were very low and the
      profiles differed from the unfired clay, it is likely that the PCDDs in dry ball
      clay were destroyed during kiln firing. These results suggest that inhalation of
      volatilized dioxins during kiln firing of dry ball clay is an unlikely source of
      exposure for vocational and art ceramicists.

PMID- 24083909
TI  - Dynamics of amphiphilic surfactants confined in montmorillonite slits with
      different cation exchange capacities.
AB  - Alkylammonium surfactants were nanoscopically confined between montmorillonite
      layers of varied negative surface charge, i.e., of varied cation exchange
      capacities. Dielectric relaxation spectroscopy was employed to probe the
      interfacial dynamics, arising from the mobility of the cations on the silicate
      surfaces, as a function of the confining walls' surface charge. Standard methods
      to dry the organo-silicates were employed; however, water was still detected
      physisorbed in the galleries; the dynamics of these water molecules were also
      detected and were found to be coupled with the dynamics of the ammoniums at high
      temperatures. A transition in the mobility of the cations, approximately at 75 
      degrees C (which is in good agreement with the conformational changes of the
      alkyl groups, reported in the literature), is observed, and a model is proposed
      on the basis of the dynamics of the confined water. Entropic contributions
      arising from variation in the surface charge density are also discussed in
      detail. The existence of water in the interlayer--in spite of drying the
      nanofillers in accordance to industrial practices--and the interrelated
      surfactant/water dynamics bring forward important implications for the design and
      processing of polymer-based nanocomposites based on these fillers.

PMID- 24083910
TI  - Primary fascial closure with mesh reinforcement is superior to bridged mesh
      repair for abdominal wall reconstruction.
AB  - BACKGROUND: Many surgeons believe that primary fascial closure with mesh
      reinforcement should be the goal of abdominal wall reconstruction (AWR), yet
      others have reported acceptable outcomes when mesh is used to bridge the fascial
      edges. It has not been clearly shown how the outcomes for these techniques
      differ. We hypothesized that bridged repairs result in higher hernia recurrence
      rates than mesh-reinforced repairs that achieve fascial coaptation. STUDY DESIGN:
      We retrospectively reviewed prospectively collected data from consecutive
      patients with 1 year or more of follow-up, who underwent midline AWR between 2000
      and 2011 at a single center. We compared surgical outcomes between patients with
      bridged and mesh-reinforced fascial repairs. The primary outcomes measure was
      hernia recurrence. Multivariate logistic regression analysis was used to identify
      factors predictive of or protective for complications. RESULTS: We included 222
      patients (195 mesh-reinforced and 27 bridged repairs) with a mean follow-up of
      31.1 +/- 14.2 months. The bridged repairs were associated with a significantly
      higher risk of hernia recurrence (56% vs 8%; hazard ratio [HR] 9.5; p < 0.001)
      and a higher overall complication rate (74% vs 32%; odds ratio [OR] 3.9; p <
      0.001). The interval to recurrence was more than 9 times shorter in the bridged
      group (HR 9.5; p < 0.001). Multivariate Cox proportional hazard regression
      analysis identified bridged repair and defect width > 15 cm to be independent
      predictors of hernia recurrence (HR 7.3; p < 0.001 and HR 2.5; p = 0.028,
      respectively). CONCLUSIONS: Mesh-reinforced AWRs with primary fascial coaptation
      resulted in fewer hernia recurrences and fewer overall complications than bridged
      repairs. Surgeons should make every effort to achieve primary fascial coaptation
      to reduce complications.

PMID- 24083912
TI  - Extensive inflammation of actinic keratoses during interferon alpha therapy for
      chronic hepatitis C in a Taiwanese albino woman.

PMID- 24083911
TI  - Patient factors associated with undergoing laparoscopic adjustable gastric
      banding vs Roux-en-Y gastric bypass for weight loss.
AB  - BACKGROUND: Roux-en-Y gastric bypass and laparoscopic adjustable gastric banding
      are 2 commonly performed bariatric procedures in the US with different profiles
      for risk and effectiveness. Little is known about factors that might lead
      patients to proceed with one procedure over the other. STUDY DESIGN: We recruited
      and interviewed patients seeking bariatric surgery from 2 academic centers in
      Boston (response rate 70%). We conducted multivariable analyses to identify
      patient perceptions and clinical and behavioral characteristics that correlated
      with undergoing gastric banding (n = 239) vs gastric bypass (n = 297). RESULTS:
      After adjustment for socio-demographic and clinical factors, we found that older
      patients (odds ratio [OR] 1.03; 95% CI 1.00 to 1.05) and those with higher
      quality of life scores and higher levels of uncontrolled eating were more likely
      to undergo gastric banding as opposed to gastric bypass. In contrast, patients
      with type 2 diabetes (OR 0.46; 95% CI 0.28 to 0.77), those who desired greater
      weight loss, and those who were willing to assume higher mortality risk to
      achieve their ideal weight were less likely to proceed with gastric banding.
      After initial adjustment, male sex and lower body mass index were associated with
      a likelihood of undergoing gastric banding; however, these factors were no longer
      significant after adjustment for other significant correlates such as patients'
      perceived ideal weight, predilection to assume risk to lose weight, and eating
      behavior. CONCLUSIONS: Patients' diabetes status, quality of life, eating
      behavior, ideal weight loss, and willingness to assume mortality risk to lose
      weight were associated with whether patients proceeded with gastric banding as
      opposed to gastric bypass. Other clinical factors were less important.

PMID- 24083913
TI  - The social-neurophysiological model of tinnitus: theory and practice.

PMID- 24083914
TI  - An innovative method to deliver treatment of military sexual trauma and post
      traumatic stress disorder.

PMID- 24083915
TI  - Fighting health care fraud in bold and innovative ways.

PMID- 24083917
TI  - Implications of psychiatric comorbidity among combat veterans.
AB  - Limited research exists regarding the rates of and outcomes associated with
      psychiatric comorbidity among active duty military personnel. This study
      investigated the rates of comorbid psychiatric diagnoses among 81,720 U.S.
      Marines, and assessed the relationships between preexisting comorbid disorders
      and risk of psychiatric hospitalizations and attrition from service. The study
      used medical, deployment, and personnel records for all Marines who enlisted
      between 2002 and 2005. The baseline rate of comorbidity was 1.3% for Marines who
      deployed during the first term of service, and 6.3% for Marines who did not
      deploy. The most common baseline comorbidity among deployed Marines was mood
      disorders with anxiety disorders, and mood and adjustment disorders among
      nondeployed Marines. Logistic regression analyses revealed Marines with comorbid
      diagnoses before deployment were over three times more likely to attrite (odds
      ratio = 3.4, p < 0.001) and over five times more likely to be hospitalized for
      psychiatric symptoms (odds ratio = 5.1, p < 0.001) following deployment than
      those with no diagnoses. Similar patterns emerged among nondeployers. Outcomes
      associated with comorbid conditions were substantially worse than outcomes for
      single conditions. These findings demonstrate that Marines with a history of
      comorbid psychiatric diagnoses are at a much greater risk for adverse outcomes,
      specifically attrition from the military and psychiatric hospitalization. 

PMID- 24083916
TI  - Post-traumatic stress disorder, depression, and aggression in OEF/OIF veterans.
AB  - Aggression is a problem among some combat veterans. Post-traumatic stress
      disorder (PTSD) is associated with physical aggression in veterans, and co
      occurring depression increases the risk of committing aggressive acts. Few
      studies have examined the impact of PTSD on various forms of aggression. While
      using a standardized multidimensional measure of aggression, this study examines
      the impact of depressive symptoms on the relationship between PTSD and various
      forms of aggression in Operation Enduring Freedom or Operation Iraqi Freedom
      (OEF/OIF) veterans. Depressive symptoms are hypothesized to mediate the
      relationship between PTSD and four types of aggression: (1) physical aggression
      toward others, (2) physical aggression toward objects, (3) physical aggression
      toward self, and (4) verbal aggression. Seventy-two OEF/OIF veterans completed
      assessment batteries and clinical interviews upon enrollment into a
      postdeployment mental health clinic. Study results partially supported the study
      hypotheses; depressive symptoms indirectly mediated the relationship between PTSD
      and two forms of aggression: verbal aggression and physical aggression toward
      self. In contrast to some prior studies of intimate partner violence in veterans
      with PTSD, no mediation relationship between depression and physical aggression
      toward others was found. Study results have implications for the development of
      interventions to treat aggressive behaviors in OEF/OIF veterans with PTSD and
      depression. 

PMID- 24083918
TI  - Psychological distress in the active duty military spine patient.
AB  - Disorders of the spine are a substantial burden to the military health care
      system that degrades readiness in the overall force. Because treatment outcomes
      are affected by psychosocial factors, assessment of psychological distress is
      important for patients with spine complaints. The incidence of psychological
      distress in the unique military population is not well described. The purpose of
      this retrospective case-control study was to determine the rate of psychological
      distress and identify associated patient characteristics among many variables
      collected in the military health system. A consecutive cohort of active duty
      service members presenting to a spine specialty clinic was assessed as Normal, At
      Risk, or Distressed using the Distress and Risk Assessment Method. Of 74 active
      duty patients (63 male, 11 female), 43 (58%) had some level of psychological
      distress: 29 (39%) At Risk, 12 (16%) Distressed-Depressive, and 2 (3%) Distressed
      Somatic. Multivariate regression analysis identified female gender (odds ratio
      [OR] 7.90), higher disability as measured by Oswestry Disability Index/Neck
      Disability Index (OR 8.0 per 13.8 point increase), and assignment to a Warrior
      Transition Unit or Medical Evaluation Board (OR 7.35) as statistically
      significant variables. The results indicate that active duty patients are subject
      to similarly high levels of psychological distress as their civilian
      counterparts. 

PMID- 24083919
TI  - Depression and pain: independent and additive relationships to anger expression.
AB  - Anger and anger expression (ANGX) are concerns in the U.S. military population
      and have been linked to stress dysregulation, heart disease, and poor coping
      behaviors. OBJECTIVE: We examined associations between depression, pain, and
      anger expression among military veterans. METHOD: Subjects (N = 474) completed a
      depression scale, a measure of pain across the last 4 weeks, and an ANGX scale. A
      multiple regression model assessed the independent and additive relationships of
      depression and pain to ANGX. RESULTS: Almost 40% of subjects met the case
      definition for either major or minor depression. Subjects reported low-to
      moderate levels of pain (mean = 6.3 of possible 20) and somewhat frequent
      episodes of ANGX. As expected, depression and pain were positively associated (r
      = 0.42, p < 0.001) and crossover effects of antidepressant and pain medication
      were shown. Specifically, frequency of antidepressant medication use was
      inversely associated with pain symptoms (r = -0.20, p < 0.001) and frequency of
      pain medication use was inversely linked to depressive symptoms (r = -0.21, p <
      0.001). In a multiple regression model, depression (beta = 0.58, p < 0.001) and
      pain (beta = 0.21, p < 0.05) showed independent and additive relationships to
      ANGX (F = 41.5, p < 0.001, R(2)adj = 0.31). CONCLUSIONS: This study offers
      empirical support for depression-pain comorbidity and elucidates independent and
      additive contributions of depression and pain to ANGX.

PMID- 24083920
TI  - Differences in what happens after you screen positive for depression versus
      hazardous alcohol use.
AB  - The success of any secondary prevention effort in identifying those in need for
      further services depends on the primary care team following all positive
      screening results with additional assessment or intervention. Initial research
      suggests possible differences in primary care responses to positive screens for
      hazardous alcohol use compared to depression. Therefore, the purpose of this
      study was to examine current practices of Veterans Affairs healthcare providers
      following a positive screen for hazardous alcohol use or depression. Chart
      reviews were conducted for a random sample of 98 Veterans who screened positive
      for hazardous alcohol use using the Alcohol Use Disorder Identification Test
      Consumption (AUDIT-C) questions and a separate sample of 99 Veterans who screened
      positive for depression using the 2-item Patient Health Questionnaire (PHQ-2)
      over a 1-year period. Findings suggest multiple discrepancies in screening
      practices between the AUDIT-C and the PHQ-2. These include a higher likelihood of
      further depression assessment or referral after a positive PHQ-2 screen. Scores
      on the AUDIT-C that indicate heavier alcohol consumption were more likely to
      result in assessment or intervention than did lower but still positive AUDIT-C
      scores. Overall, these data suggest that many opportunities are missed,
      especially in regards to hazardous alcohol use, for prevention and intervention. 

PMID- 24083921
TI  - Drug positive rates for the Army, Army Reserve, and Army National Guard from
      fiscal year 2001 through 2011.
AB  - OBJECTIVE: To examine the overall and drug-specific positive rates of Army
      urinalysis specimens tested from fiscal year 2001 (FY01) through FY11. METHODS:
      We analyzed annual Army Forensic Toxicology Drug Testing Laboratory results from
      FY01 to FY11. RESULTS: From FY01 to FY11, the Army's positive rate was 1.06%. The
      component rates were 0.84%, 1.53%, and 1.94% for the active duty, Reserve, and
      National Guard, respectively. The Army's average positive rate for marijuana from
      FY01 to FY11 was 0.79%, and the cocaine rate was 0.26%. From FY06 to FY11, the
      average positive rate for oxycodone was 0.74% and the d-amphetamine rate was
      0.30%. Apart from oxymorphone, a key metabolite of oxycodone, the positive rate
      for all other drugs tested was below 0.25%. The FY11 drug positive rates in
      decreasing order were oxymorphone > oxycodone > marijuana > d-amphetamine >
      codeine > cocaine > morphine > d-methamphetamine > methylenedioxymethamphetamine
      > heroin > methylenedioxyamphetamine > phencyclidine. Although the drug positive
      rate for heroin remains low, the number of positives has increased dramatically
      since FY05. CONCLUSION: The drug-testing program continues to serve as a vital
      deterrent as evidenced by the Army's overall positive rate being well below the
      8.9% estimated illicit use in the civilian population.

PMID- 24083922
TI  - Creation of a criterion-referenced Military Optimal Performance Challenge.
AB  - PURPOSE: To compare an empirical, Army doctrine-based (endurance, strength,
      mobility, military relevant tasks), criterion-referenced, body mass (BM) unbiased
      Military Optimal Performance Challenge (MOPC) to the Army's Physical Fitness Test
      (APFT) and thus assisting commanders to determine military readiness. METHODS:
      Militarily-relevant physical assessments were combined to create a composite MOPC
      score. The MOPC and APFT were administered to 20 male, military subjects during a
      2-week period. Data collection included 3-Mile Run, Mobility Test, Upper/Lower
      Body Strength/Endurance, Simulated Casualty Evacuation Test. The APFT was
      administered through Army guidelines before MOPC data collection. RESULTS: The
      APFT was influenced by BM, lean body mass (LBM) (r = -0.44; r(2) = 0.20; p =
      0.04), whereas MOPC was less impacted (r = 0.21; r(2) = 0.04; p = 0.32). Eight
      subjects, as viewed by %APFT, are "fit for duty" (80.6%); however, all eight
      subjects' mean score as %MOPC was <50%. CONCLUSIONS: The MOPC offers a robust
      approach to military readiness and is free of the confounding influence of BM.
      The MOPC is a unique assessment requiring a multitude of abilities to garner
      success and may assist in training for functional combat performance skills
      demanding high work capacities.

PMID- 24083923
TI  - Cost-effectiveness analysis of the U.S. Army Assessment of Recruit Motivation and
      Strength (ARMS) program.
AB  - The Assessment of Recruit Motivation and Strength (ARMS) Study was conducted at
      six Military Entrance Processing Sites during 2005-2006. The objectives were to
      compare morbidity and attrition of Army accessions who exceeded body fat (EBF)
      accession standards compared to weight for height or body fat qualified (WQ) and
      to compare among the WQ subset, those who were physically fit as measured by a 5
      minute step test compared to unfit. We performed a cost-effectiveness analysis to
      address both objectives. Analysis was performed by gender with the primary
      outcomes of musculoskeletal injury and attrition. Results were expressed in terms
      of cost per year of military service. Sensitivity analysis was performed on
      probability cost estimates. We found WQ female recruits were $5,141 less
      expensive per year than EBF female recruits. WQ males were $2,785 less expensive
      per year of military service than EBF male recruits. Among WQ recruits, fit
      females were $3,638 and fit males were $10,381 less expensive per year of service
      than their unfit counterparts. The ARMS step test is a cost-effective method to
      identify physically fit EBF applicants for accession in weak recruiting
      environments. It also offers a cost-effective method to reduce poor physical
      fitness associated morbidity and attrition. 

PMID- 24083924
TI  - Patient greeting preferences for themselves and their providers in a military
      family medicine clinic.
AB  - Using the proper greeting may be important to help establish rapport between
      health care providers and their patients. It may be particularly useful for
      family medicine physicians working in a military medical facility, where military
      rank and traditions are important. A total of 259 anonymous surveys were
      collected from patients treated at a military family medicine clinic. Most of the
      patients who completed the survey preferred to shake hands with their provider,
      be greeted using only their first name, and preferred that the provider introduce
      themselves using their last name only. Active duty patients were more likely than
      civilians to prefer a handshake (odds ratio [OR] 3.05, 95% confidence interval
      [CI] 1.46-6.39) and officers were more likely to prefer a handshake compared to
      enlisted service members (OR 3.29; 95% CI 1.18-9.20). Respondents who were older
      were more likely to prefer a formal introduction by their provider compared to
      respondents under 35 years old (OR 2.92, 95% CI 1.35-6.31). Although most
      patients in this facility expressed a preference for how they would like to be
      greeted, providers are still encouraged to ask their patients how they would
      prefer to be addressed. 

PMID- 24083925
TI  - Effectiveness of physical therapists serving as primary care musculoskeletal
      providers as compared to family practice providers in a deployed combat location:
      a retrospective medical chart review.
AB  - OBJECTIVES: A medical records review to compare efficiency and effectiveness of a
      physical therapist (PT) functioning as a musculoskeletal primary care provider
      (PCP) compared to family practice (FP) physicians functioning as musculoskeletal
      PCP. HYPOTHESIS: (1) Use of medication/imaging studies will be significantly less
      with a PT as PCP compared to FP as PCP. (2) Return-to-duty (RTD) rate will show
      significant increases when patients with musculoskeletal conditions are seen by
      PT as compared to FP. METHODS: One PT practicing in a deployed combat location
      collected data on patients that presented directly to the PT clinic or FP clinic
      for care of musculoskeletal complaints. Treatment patterns of two Air Force
      physicians were accessed regarding patients with musculoskeletal conditions.
      Fifty-four patients were randomly selected for the PT group and 95 patients for
      FP group. AHLTA was searched for cases reported from June 2009 to January 2010.
      Data regarding age, gender, medication, imaging use, and return to duty (RTD)
      rate were collected. RESULTS: Of the study population, 126 (84%) were males, 23
      (16%) were females (age range: 19-54, mean 29). RTD rate was 50% greater for PT.
      Rate of medication and imaging use for PT was 24% and 11%, whereas FP was 90% and
      82%, respectively (p < 0.01). CONCLUSION: Using PT as the musculoskeletal PCP was
      shown to be an effective and efficient practice model to assess and treat
      patients with musculoskeletal complaints.

PMID- 24083926
TI  - Prevalence of prehospital hypoxemia and oxygen use in trauma patients.
AB  - OBJECTIVE: This study estimates the prevalence of injured patients requiring
      prehospital supplemental oxygen based on existing recommendations, and determines
      whether actual use exceeds those recommendations. PATIENTS AND METHODS:
      Prehospital oxygen use and continuous peripheral oxygen saturation measurements
      were prospectively collected on a purposive sample of injured civilians
      transported to an urban level 1 trauma center by paramedics. Structured chart
      review determined injury characteristics and outcomes. Supplemental oxygen
      administration indications were hypoxemia (peripheral oxygen saturation <= 90%),
      hemorrhagic shock (systolic blood pressure < 100 mmHg), or paramedic suspicion of
      traumatic brain injury. RESULTS: Paramedics enrolled 224/290 screened subjects.
      Median (range) age was 34 (18-84) years, 48.7% were nonwhite, 75.4% were male,
      and Injury Severity Score was 5 (1-75). Half (54.5%) were admitted; 36.2%
      sustained a penetrating injury. None underwent prehospital endotracheal
      intubation. Hypoxemia occurred in 86 (38.4%), paramedics suspected traumatic
      brain injury in 22 (9.8%), and 20 (8.9%) were hypotensive. Any indication for
      supplemental oxygen (107/224 [47.8%, 95%CI 41.3%-54.3%]) and prehospital
      administration of oxygen (141/224 [62.9%, 95%CI 56.2%-69.2%]) was common. Many
      (35/141 [24.8%]) received oxygen without indication. CONCLUSIONS: On the basis of
      current guidelines, less than half of adult trauma patients have an indication
      for prehospital supplemental oxygen, yet is frequently administered in the
      absence of clinical indication.

PMID- 24083927
TI  - Knowledge, attitudes, and practice regarding HIV testing among female military
      family members of childbearing age in Honduras.
AB  - This is a survey of knowledge, attitudes, and practice regarding HIV testing
      among 187 female family members affiliated with the Honduran Armed Forces and
      civilian controls. Prior HIV testing was reported by 45%, and 94% expressed
      willingness to be tested in the future. Pregnancy was the reason for 73% of prior
      tests, but only 49% of the 149 women with prior pregnancies reported prior tests.
      Although most women tested for HIV did so during pregnancy, there appears to be a
      gap in understanding that the rationale is to help prevent maternal-child
      transmission at birth or through breast-feeding. Military-affiliated women were
      more likely to describe themselves as being knowledgeable of HIV/AIDS, 95% versus
      82% (p < 0.01), but there were few differences in knowledge between groups.
      Positive perceptions of confidentiality, test accuracy, and self-awareness of HIV
      were associated with prior testing. Although these differences may point to
      HIV/AIDS educational areas that should be emphasized for a particular population,
      the overall content that should be provided to military or civilian families is
      the same. 

PMID- 24083928
TI  - Tdap coverage in a military beneficiary population: room for improvement.
AB  - Pertussis has had a resurgence in recent years. Women of child-bearing age and
      adults with infant contact are important reservoirs of infection because of
      waning immunity. Recent infant deaths and outbreaks led to new tetanus,
      diphtheria, and acellular pertussis (Tdap) vaccine recommendations, but
      vaccination rates remain low. A performance improvement project was started at
      Walter Reed Army Medical Center to target women of child-bearing age. Women
      treated in Gynecology had their electronic medical record screened for Tdap
      during their vital signs assessment. Those eligible for vaccination were directed
      to the Immunization Clinic. The intervention was considered successful if the
      patient received the vaccine within 30 days of the visit. Data were compiled on
      vaccination rates 1 month before and 1 and 3 months after the start of the
      performance improvement project. Only 13.9% of all patients had a documented Tdap
      at any time. During the first month following the intervention, vaccination rates
      within 30 days of the appointment increased from 0.38% to 6.5% (p < 0.005). The
      effect waned at 3 months following intervention, with only 1.1% of patients
      vaccinated within 30 days of the appointment. Overall vaccination rates remain
      low, and future studies should focus on barriers to vaccination to prevent
      morbidity and mortality. 

PMID- 24083929
TI  - Prevalence of abnormal serum lipids among overweight and obese soldiers.
AB  - The U.S. military is not immune to the obesity epidemic occurring in the United
      States and its negative health impacts. We conducted a study to determine the
      prevalence of abnormal serum lipid concentrations in overweight and obese U.S.
      Soldiers at Fort Bliss, TX. This was a cross-sectional, retrospective study of
      medical records of Soldiers who attended weight management classes. Study
      population consisted of 659 Soldiers who had at least one laboratory measure of
      serum lipids. The mean age of the Soldiers was 29 years and 69% were classified
      as obese. The prevalence of total cholesterol above the desirable limit of 200
      mg/dL was 30% for men and 16% for females. Seventy percent of males and 46% of
      females had a low-density lipoprotein concentration above the optimal level of
      100 mg/dL. Twenty-nine percent of males had elevated triglyceride levels. The
      odds of having elevated triglycerides were significantly higher among Soldiers
      who were older, male, obese, and used tobacco. The risk of elevated serum lipid
      levels and associated modifiable risk factors in this group of young Soldiers is
      concerning. 

PMID- 24083930
TI  - Thermal-work strain during Marine rifle squad operations in Afghanistan.
AB  - The physiological burden created by heat strain and physical exercise, also
      called thermal-work strain, was quantified for 10 male Marines (age 21.9 +/- 2.3
      years, height 180.3 +/- 5.2 cm, and weight 85.2 +/- 10.8 kg) during three
      dismounted missions in Helmand Province, Afghanistan. Heart rate (HR) and core
      body temperature (T core) were recorded every 15 seconds (Equivital EQ-01;
      Hidalgo, Cambridge, United Kingdom) during periods of light, moderate, and heavy
      work and used to estimate metabolic rate. Meteorological measures, clothing
      characteristics, anthropometrics, and estimated metabolic rates were used to
      predict T core for the same missions during March (spring) and July (summer)
      conditions. Thermal-work strain was quantified from HR and T core values using
      the Physiological Strain Index (PSI) developed by Moran et al. July PSI and T
      core values were predicted and not observed due to lack of access to in-theater
      warfighters at that time. Our methods quantify and compare the predicted and
      observed thermal-work strain resulting from environment and worn or carried
      equipment and illustrate that a small increase in ambient temperature and solar
      load might result in increased thermal-work strain.

PMID- 24083931
TI  - Fever acquired overseas is not always infectious in etiology: adult-onset Still's
      disease in a soldier deployed to Afghanistan.
AB  - Adult-onset Still's disease (AOSD) is a rare systemic inflammatory disorder of
      unknown etiology characterized by spiking fever, arthritis or arthralgia, rash,
      and leukocytosis. The nonspecific findings and epidemiology of the disease can
      complicate the diagnosis among deployed U.S. personnel, because they are exposed
      to infectious etiologies that can present in a similar fashion. We present a case
      of 19-year-old U.S. Army soldier who was deployed to Afghanistan and eventually
      medevaced to Walter Reed National Military Medical Center complaining of
      arthralgia, diffuse myalgia, daily spiking fever, and laboratory abnormalities
      including leukocytosis and elevated liver-associated enzymes. After an initial
      concern for an infectious etiology, the patient met Yamaguchi criteria for the
      diagnosis for AOSD. The patient's clinical course, pertinent laboratory, and
      pathology data are reviewed in the context of approaching the diagnosis and
      treatment of AOSD. This case highlights that providers need to maintain a high
      clinical suspicion for less common conditions such as AOSD in the setting of
      unresolving nonspecific findings such as fever, rash, and leukocytosis. 

PMID- 24083933
TI  - Rabies, readiness, and role 1 medical care.
AB  - As medics and doctors prepare for deployment to a combat zone, there are
      countless specified and implied tasks needed to prepare the medical support of an
      Infantry unit in theater. Appropriately, units spend the lion share of their
      efforts in trauma training and medical readiness (vaccinations, medication
      prescriptions, eye glasses, etc.) while ensuring that the sets, kits, and outfits
      are all fully stocked with the required items needed to execute the mission.
      Unfortunately, this training and preparation included little on the major
      challenges units currently face from rabies. With the unfortunate recent death of
      a soldier from rabies, medical personnel were required to become experts in
      animal control, the prevention of animal bites and scratches, and the most
      appropriate treatment of service members with potential exposure to rabid
      animals. This article will discuss the challenges of rabies management in
      Afghanistan, appropriate provider and unit preparation to minimize risk of
      developing rabies, the need for establishment of an animal control team and
      prerequisite training of soldiers, leaders, and medics before and during
      deployment. Finally, we will review published guidelines for treating individuals
      exposed to rabies with a discussion of our units experience with postexposure
      prophylaxis. 

PMID- 24083932
TI  - Guillain-Barre variant in the deployed setting.
AB  - Guillain-Barre syndrome (GBS) is a pleomorphic condition with multiple clinical
      presentations. Atypical presentations may elude diagnosis particularly in the
      deployed setting or austere environment where diagnostic resources are limited. I
      describe a soldier who developed an unusual GBS variant while deployed to Iraq.
      Diagnosing and treating GBS in the deployed setting or in a rural, austere
      environment is challenging, but there are clinical guidelines that can help
      determine who can be treated locally and who needs evacuation. Recognizing the
      natural course of the disease and being able to prognosticate progression of the
      disease is crucial in deployed settings/austere environments. The diagnostic and
      therapeutic approach to GBS in the deployed setting and potential criteria for
      theater evacuation are reviewed. 

PMID- 24083934
TI  - Transcatheter closure of secundum-type atrial septal defect after failed surgical
      intervention.
AB  - INTRODUCTION: Atrial septal defect (ASD) closure is routinely performed using
      transcatheter closure under echocardiographic guidance. CASE DESCRIPTION: A 24
      year-old male was evaluated for a newly detected heart murmur. This was the first
      time a murmur or any other cardiac abnormalities were detected. He reported no
      symptoms of chest pain, dyspnea, palpitations, and reported being able to run
      without limitations. Physical examination revealed a short-grade systolic murmur
      consistent with high pulmonary flow in the left sternal border. A transesophageal
      echocardiogram revealed a 28-mm secundum ASD with right ventricular and right
      atrial enlargement. Percutaneous closure device was initially contemplated but
      was deferred secondary to the size of ASD and the lack of inferior rim. He then
      underwent open surgical closure, which was complicated by reoperation for
      bleeding and incomplete ASD closure. However, the surgery provided a new generous
      inferoposterior rim from scar tissue to perform percutaneous closure. DISCUSSION:
      This case illustrates an example of a patient with a significant ASD with an
      initially inadequate rim to perform a successful percutaneous closure. Following
      a failed surgical closure, the patient had developed enough scar tissue in the
      previously inadequate rim to undergo a successful percutaneous closure that
      resolved his defect.

PMID- 24083935
TI  - Cholestatic liver injury associated with dietary supplements: a report of five
      cases in active duty service members.
AB  - The use of dietary supplements (DS) is common in the active duty population,
      often without physician knowledge or approval. DS have been associated with drug
      induced liver injury, with rare cases resulting in liver failure or death. We
      report five cases of transient drug-induced liver injury temporally associated
      with the use of a total of six DS in active duty service members. All patients
      presented with elevated serum bilirubin and liver-associated enzymes: three
      patients had a cholestatic liver enzyme pattern, one had a hepatocellular
      pattern, and one had a mixed pattern. In all cases, percutaneous needle core
      biopsies of the liver were obtained and demonstrated a cholestatic pattern of
      injury with variable periportal fibrosis. Causality was considered highly
      probable for three cases, probable for one case, and possible for one case.
      Hepatotoxicity has been previously associated with four of the supplements in our
      cases. For the two remaining supplements, C4 Extreme and Animal Stak, we are
      unaware of any previous reports of hepatotoxicity. Health care professionals, in
      particular military physicians, should be aware of the potential risk of these
      supplements and be prepared to discuss these risks with their patients. 

PMID- 24083936
TI  - Programmes and prospects for ovotechnology.
AB  - Oocytes hold enormous significance in biology, pathology and ageing, but they are
      exceedingly rare cells in adults. According to a theory almost universally held
      until recently, expansion of the germline is halted perinatally when oogonial
      stem cells differentiate to form to primordial follicles. Thus, there is a finite
      follicle store which becomes exhausted around the time of menopause because the
      great majority is lost by atresia instead of undergoing ovulation. While FSH
      treatment can rescue a few follicles that would otherwise degenerate, in-vitro
      growth together with in-vitro maturation can potentially yield much larger
      harvests of oocytes, up to the limited number of primordial follicles available.
      If, however, germline stem cells persist after birth, enabling new oocytes to be
      generated, oogenesis is no longer bound by an upper limit. Even if they
      disappeared, as current theory prescribes, proliferative germline cells might be
      created de novo either from embryonic stem cells or through induced pluripotent
      stem cell technology. This paper reviews the prospects for a new road map for
      discovery research aimed at creating technologies to overcome the shortage of
      oocytes, which would have a revolutionary impact on IVF treatment, egg donation,
      premature ovarian insufficiency and regenerative medicine.

PMID- 24083937
TI  - Survived spondyloptosis of the thoracic spine in the Early Middle Ages (Czech
      Republic).
AB  - At a Slavic site Pohansko near Breclav (Czech Republic), at the burial ground
      around the church (9th-10th century) 757 skeletons (208 males, 159 females, 354
      sub-adults and 36 undetermined individuals), were excavated. More or less
      complete vertebral column was preserved in 109 adults. Among those, in the grave
      number 403, the skeletal remains of an adult male were found with the deformity
      of the spine probably caused by severe trauma (spondyloptosis). Due to the poor
      preservation of the caudal part of the spine, we cannot exclude diagnoses
      including spondylitis tuberculosa and developmental defects of the spine such as
      the persistence of neurocentral synchondroses, or the retrosomatic cleft.
      Considering the first possible diagnosis to be the most probable, it would be the
      first survived case of spondyloptosis identified in the palaeopathological
      literature.

PMID- 24083938
TI  - High-activity mesoporous Pt/Ru catalysts for methanol oxidation.
AB  - High activity mesoporous Pt/Ru catalysts with 2D-hexagonal structure were
      synthesized using a triblock poly(ethylene oxide)-b-poly(propylene oxide)-b
      poly(ethylene oxide) copolymer (Pluronic F127) template. The normalized mass
      activities for the methanol oxidation reaction (MOR) of the Pt/Ru catalysts with
      a regular array of pores is higher than those reported for nanoparticulated Pt/Ru
      catalysts. Different kinetic parameters, as Tafel slope and activation energy,
      were obtained for the MOR on the mesoporous catalysts. Results indicated that
      catalysts performance depends on pore size. Mass activities and the CO2
      conversion efficiency for large pore size mesoporous catalysts (10 nm) are
      greater than those reported for smaller pore size mesoporous catalysts with
      similar composition. The effect of pore size on catalysts performance is related
      to the greater accessibility of methanol to the active areas inside large pores.
      Consequently, the overall residence time of methanol increases as compared with
      mesoporous catalyst with small pores. 

PMID- 24083939
TI  - Menaquinone biosynthesis: formation of aminofutalosine requires a unique radical
      SAM enzyme.
AB  - Menaquinone (MK, vitamin K2) is a lipid-soluble molecule that participates in the
      bacterial electron transport chain. In mammalian cells, MK functions as an
      essential vitamin for the activation of various proteins involved in blood
      clotting and bone metabolism. Recently, a new pathway for the biosynthesis of
      this cofactor was discovered in Streptomyces coelicolor A3(2) in which chorismate
      is converted to aminofutalosine in a reaction catalyzed by MqnA and an
      unidentified enzyme. Here, we reconstitute the biosynthesis of aminofutalosine
      and demonstrate that the missing enzyme (aminofutalosine synthase, MqnE) is a
      radical SAM enzyme that catalyzes the addition of the adenosyl radical to the
      double bond of 3-[(1-carboxyvinyl)oxy]benzoic acid. This is a new reaction type
      in the radical SAM superfamily. 

PMID- 24083940
TI  - Methanol fixation of plant tissue for Scanning Electron Microscopy improves
      preservation of tissue morphology and dimensions.
AB  - BACKGROUND: It is well known that preparation of biological (plant and animal)
      tissues for Scanning Electron Microscopy (SEM) by chemical fixation and critical
      point drying results in shrinkage of tissues, often by up to 20-30%, depending on
      the tissue type and fixation protocol used. We sought to identify a protocol that
      would preserve tissue size and morphology better than standard chemical fixatives
      and dehydration regimes. We compared a range of processing techniques by
      quantifying changes in tissue size and recording details of surface morphology
      using leaf tissues from three commonly studied species; Arabidopsis thaliana,
      barley and cotton. RESULTS: All processing protocols altered tissue dimensions.
      Methanol fixation and dehydration, followed by a further short (1 h) dehydration
      step in ethanol and critical point drying (which was based on a previously
      published method), preserved tissue dimensions most consistently of all protocols
      tested, although it did cause 8% shrinkage in all three species. This protocol
      was also best for preservation of surface morphology in all three species. We
      outline a recommended protocol and advise that the method is best trialled for
      different tissues, especially thicker or larger samples. CONCLUSIONS: This study
      shows that simultaneous fixation and dehydration in methanol followed by ethanol
      results in better preservation of dimensions and morphology of critical point
      dried plant tissues than other fixation and dehydration procedures. It is a quick
      and simple method, and requires standard SEM preparation equipment.

PMID- 24083941
TI  - Nonhydrolyzable ATP analogues as selective inhibitors of human NPP1: a combined
      computational/experimental study.
AB  - Elevated nucleotide pyrophosphatase/phosphodiesterase-1 (NPP1) activity is
      implicated in health disorders including pathological calcification. Specific
      NPP1 inhibitors would therefore be valuable for studying this enzyme and as
      potential therapeutic agents. Here we present a combined
      computational/experimental study characterizing 13 nonhydrolyzable ATP analogues
      as selective human NPP1 inhibitors. All analogues at 100 MUM inhibited (66-99%)
      the hydrolysis of pnp-TMP by both recombinant NPP1 and cell surface NPP1 activity
      of osteocarcinoma (HTB-85) cells. These analogues only slightly altered the
      activity of other ectonucleotidases, NPP3 and NTPDases. The Ki,app values of the
      seven most potent and selective inhibitors were in the range of 0.5-56 MUM, all
      with mixed type inhibition, predominantly competitive. Those molecules were
      docked into a newly developed homology model of human NPP1. All adopted ATP-like
      binding modes, suggesting competitive inhibition with the endogenous ligand. NPP1
      selectivity versus NPP3 could be explained in terms of the electrostatic
      potential of the two proteins that of NPP1 favoring negatively charged ligands.
      Inhibitor 2 that had the lowest Ki,app (0.5 MUM) was also inactive toward P2Y
      receptors. Overall, analogue 2 is the most potent and selective NPP1 inhibitor
      described so far. 

PMID- 24083943
TI  - Effects of a commercial canine gonadotropin releasing hormone vaccine on estrus
      suppression and estrous behavior in mares.
AB  - We investigated the effect of immunization against gonadotropin releasing hormone
      (GnRH) using a commercial canine GnRH vaccine on estrus suppression and unwanted
      estrous behavior in mares. In experiment 1, mares were immunized (n = 6) twice
      with vaccine (5 mL) given intramuscularly 4 weeks apart or received a control
      diluent (n = 5). Transrectal ultrasonographic examination of the reproductive
      tracts was performed three days a week for 40 weeks after initial vaccination.
      Blood samples were collected weekly for GnRH antibody titer and progesterone
      concentration determination. In experiment 2, privately-owned mares (n = 12) were
      immunized twice with vaccine (1 mL) given intramuscularly 4 weeks apart. Blood
      samples were collected prior to each vaccination as well as 12 and 20 weeks after
      initial treatment, and transrectal ultrasonographic examinations of the
      reproductive tracts were performed 12 weeks after the first vaccination.
      Vaccinated mares in experiment 1 responded with a GnRH antibody titer,
      progesterone concentrations significantly lower than controls, and cessation of
      ovarian activity. Vaccinated mares in experiment 2 also responded with a GnRH
      antibody titer, progesterone concentrations that remained basal for the duration
      of the study, and cessation of ovarian activity. Owners of vaccinated mares in
      experiment 2 reported that the number of unwanted estrous behaviors present
      before vaccination significantly decreased following vaccination. In conclusion,
      GnRH immunization using a canine GnRH vaccine is an effective method for
      suppressing estrus and unwanted estrous behavior.

PMID- 24083944
TI  - Home oxygen therapy for infants and young children with acute bronchiolitis and
      other lower respiratory tract infections: the HiTHOx program.
AB  - BACKGROUND: Acute lower respiratory tract infection (LRTI) including
      bronchiolitis, is one of the leading causes of pediatric hospital admissions
      worldwide. Recent studies have demonstrated that some children with acute
      bronchiolitis can be successfully managed using home oxygen therapy. AIM: To
      report the impact of a Hospital in The Home Oxygen therapy program (HiTHOx) for
      selected infants and young children with acute bronchiolitis and other LRTI.
      FINDINGS: The HiTHOx program appears to be a safe model of care for carefully
      selected infants and young children with acute bronchiolitis and LRTI that
      reduces the hospital length of stay. CONCLUSIONS: The HiTHOx program provides an
      alternative model of care for infants and young children with acute LRTI.
      Implementation of models of care similar to that of the HiTHOx program in other
      pediatric health services may have the potential to create additional bed
      capacity, at the time of year when it is most needed.

PMID- 24083942
TI  - Body mass index in chronic heart failure: association with biomarkers of
      neurohormonal activation, inflammation and endothelial dysfunction.
AB  - BACKGROUND: Low body mass index (BMI) is associated with a poor outcome in
      chronic heart failure (CHF). An inverse association between BMI and adiponectin
      and N-terminal pro-B-type natriuretic peptide (NT-proBNP) has been reported. The
      aim of the present study was to investigate whether novel markers of
      neurohormonal activation, inflammation, and endothelial dysfunction are
      associated with BMI in CHF. METHODS: In a cross-sectional study including 171
      patients with CHF and a left ventricular ejection fraction (LVEF) <=45% the
      impact of BMI on circulating plasma concentrations of adiponectin, alpha
      defensins, high sensitivity C-reactive protein (hsCRP), copeptin, mid-regional
      pro-adrenomedullin (MR-proADM), NT-proBNP, and mid-regional pro-A-type
      natriuretic peptide (MR-proANP) were evaluated. RESULTS: In multivariable linear
      regression analysis including age, sex, LVEF, New York Heart Association
      functional classification (NYHA), estimated glomerular filtration rate (eGFR),
      and diabetes, only NT-proBNP (beta = -0.32) and adiponectin (beta = -0.39)
      remained independently associated with BMI. MR-proANP was associated with BMI but
      adjusting for age attenuated the relation being no longer significant.
      CONCLUSIONS: Among biomarkers typically increased in patients with CHF only
      adiponectin and NT-proBNP demonstrated independent inverse associations with BMI.
      This indicates a direct effect of these two biomarkers enhancing the wasting
      process seen in CHF.

PMID- 24083945
TI  - Co-existence of classical and alternative activation programs in macrophages
      responding to Toxoplasma gondii.
AB  - Pro-inflammatory M1 macrophages are critical for defense against intracellular
      pathogens while alternatively-activated M2 macrophages mediate tissue homeostasis
      and repair. Whether these distinct activation programs are mutually exclusive or
      can co-exist within the same cell is unclear. Here, we report the co-existence of
      these programs in Toxoplasma gondii-elicited inflammatory macrophages. This is
      independent of parasite expression of the virulence factor ROP16 and host cell
      expression of signal transducer and activator of transcription 6 (STAT6).
      Furthermore, this observation was recapitulated by IFN-gamma and IL-4 treated
      bone marrow-derived macrophages in vitro. These results highlight the multi
      functionality of macrophages as they respond to diverse microbial and endogenous
      stimuli. 

PMID- 24083946
TI  - Fate of Escherichia coli O157:H7 and Salmonella enterica in the manure-amended
      soil-plant ecosystem of fresh vegetable crops: a review.
AB  - Enterohemorrhagic Escherichia coli (EHEC) and Salmonella enterica have been
      implicated in several disease outbreaks linked to consumption of fresh
      vegetables. Both ruminant and non-ruminant animals carry EHEC and S. enterica in
      their gastrointestinal tracts and can shed the pathogens in the faecal matter
      both in symptomatic and asymptomatic states. Application of animal waste in soil
      fertility management and irrigation of crops with contaminated waste water has
      been recognised as an important route through which EHEC and S. enterica can
      contaminate fresh vegetables during primary production. The behavior of E. coli
      O157:H7 and S. enterica in the agricultural environment has been extensively
      studied in the last decades. Several microbiological detection methods have been
      applied. This review therefore puts together current knowledge on the behavior of
      E. coli O157:H7 and S. enterica in the manure-amended soil-plant ecosystem of
      fresh vegetable crops during cultivation under various environmental conditions.
      The review focuses on methodological issues involved in undertaking survival
      studies and makes comparative analysis of experimental results obtained from
      studies conducted under controlled environmental conditions integrating results
      obtained from field experiments. Finally, a theoretical discussion on the
      potential likely impact of climate change on pre-harvest safety of field
      cultivated vegetables is highlighted. 

PMID- 24083948
TI  - Fast detection of drug interaction in Mycobacterium tuberculosis by a
      checkerboard resazurin method.
AB  - Tuberculosis (TB) is a health public problem and a long combination therapy is
      necessary to treat patients. In recent years, some drugs, not routinely used in
      treatment of TB, have appeared as promising new anti-TB therapies in patients
      with resistance to classical drugs. The aim of this study was: (i) to evaluate a
      modified checkerboard assay, Resazurin drugs combination microtiter assay (REDCA)
      to detect drugs interaction in Mycobacterium tuberculosis; (ii) to evaluate the
      interaction between isoniazid (INH) or ethambutol (EMB) with levofloxacin (LEVO)
      in susceptible and resistant M. tuberculosis Brazilian clinical isolates. M.
      tuberculosis H37RV ATCC 27294 and 19 clinical isolates (10 resistant and 9
      susceptible) were tested. The fractional inhibitory concentration index (FICI) <=
      0.5 was considered synergistic. Synergism in M. tuberculosis H37RV and resistant
      M. tuberculosis Brazilian isolates was observed with EMB vs. LEVO. No synergism
      was observed with INH vs. LEVO by both assays. No statistical difference was
      observed by the two assays studied. REDCA showed to be a simple assay for
      detecting synergism between drugs in M. tuberculosis. The results with EMB vs.
      LEVO are promising and it can be a new option in future investigations of drugs
      interactions against M. tuberculosis with the view to reduce EMB adverse effects.

PMID- 24083947
TI  - Different virulence of porcine and porcine-like bovine rotavirus strains with
      genetically nearly identical genomes in piglets and calves.
AB  - Direct interspecies transmissions of group A rotaviruses (RVA) have been reported
      under natural conditions. However, the pathogenicity of RVA has never been
      directly compared in homologous and heterologous hosts. The bovine RVA/Cow
      tc/KOR/K5/2004/G5P[7] strain, which was shown to possess a typical porcine-like
      genotype constellation similar to that of the G5P[7] prototype RVA/Pig
      tc/USA/OSU/1977/G5P9[7] strain, was examined for its pathogenicity and compared
      with the porcine G5P[7] RVA/Pig-tc/KOR/K71/2006/G5P[7] strain possessing the same
      genotype constellation. The bovine K5 strain induced diarrhea and
      histopathological changes in the small intestine of piglets and calves, whereas
      the porcine K71 strain caused diarrhea and histopathological changes in the small
      intestine of piglets, but not in calves. Furthermore, the bovine K5 strain showed
      extra-intestinal tropisms in both piglets and calves, whereas the porcine K71
      strain had extra-intestinal tropisms in piglets, but not in calves. Therefore, we
      performed comparative genomic analysis of the K71 and K5 RVA strains to determine
      whether specific mutations could be associated with these distinct clinical and
      pathological phenotypes. Full-length sequencing analyses for the 11 genomic
      segments for K71 and K5 revealed that these strains were genetically nearly
      identical to each other. Two nucleotide mutations were found in the 5'
      untranslated region (UTR) of NSP5 and the 3' UTR of NSP3, and eight amino acid
      mutations in VP1-VP4 and NSP2. Some of these mutations may be critical molecular
      determinants for RVA virulence and/or pathogenicity.

PMID- 24083949
TI  - Structural basis of the substrate specificity of cytidine deaminase superfamily
      Guanine deaminase.
AB  - Guanine deaminases (GDs) are important enzymes involved in purine metabolism as
      well as nucleotide anabolism pathways that exhibit a high degree of fidelity.
      Here, the structural basis of the substrate specificity of GDs was investigated
      by determining a series of X-ray structures of NE0047 (GD from Nitrosomonas
      europaea) with nucleobase analogues and nucleosides. The structures demonstrated
      that the interactions in the GD active site are tailor-made to accommodate only
      guanine and any substitutions in the purine ring or introduction of a pyrimidine
      ring results in rearrangement of the bases in a catalytically unfavorable
      orientation, away from the proton shuttling residue E143. In addition, X-ray
      structural studies performed on cytidine revealed that although it binds in an
      optimal conformation, its deamination does not occur because of the inability of
      the enzyme to orchestrate the closure of the catalytically important C-terminal
      loop (residues 181-189). Isothermal calorimetry measurements established that
      these nucleoside moieties also disrupt the sequential mode of ligand binding,
      thereby abrogating all intersubunit communication. Intriguingly, it was recently
      discovered that GDs can also serve as endogenous ammeline deaminases, although it
      is structurally nonhomologous with guanine. To understand the mechanism of dual
      substrate specificity, the structure of NE0047 in complex with ammeline was
      determined to a resolution of 2.7 A. The structure revealed that ammeline not
      only fits in the active site in a catalytically favorable orientation but also
      allows for closure of the C-terminal loop. 

PMID- 24083950
TI  - The novel anti-inflammatory agent VA694, endowed with both NO-releasing and COX2
      selective inhibiting properties, exhibits NO-mediated positive effects on blood
      pressure, coronary flow and endothelium in an experimental model of hypertension
      and endothelial dysfunction.
AB  - Selective cyclooxygenase 2 (COX2) inhibitors (COXIBs) are effective anti
      inflammatory and analgesic drugs with improved gastrointestinal (GI) safety
      compared to nonselective nonsteroidal anti-inflammatory drugs known as
      traditional (tNSAIDs). However, their use is associated with a cardiovascular
      (CV) hazard (i.e. increased incidence of thrombotic events and hypertension) due
      to the inhibition of COX2-dependent vascular prostacyclin. Aiming to design COX2
      selective inhibitors with improved CV safety, new NO-releasing COXIBs (NO-COXIBs)
      have been developed. In these hybrid drugs, the NO-mediated CV effects are
      expected to compensate for the COXIB-mediated inhibition of prostacyclin. This
      study evaluates the potential CV beneficial effects of VA694, a promising NO
      COXIB, the anti-inflammatory effects of which have been previously characterized
      in several in vitro and in vivo experimental models. When incubated in hepatic
      homogenate, VA694 acted as a slow NO-donor. Moreover, it caused NO-mediated
      relaxant effects in the vascular smooth muscle. The chronic oral administration
      of VA694 to young spontaneously hypertensive rats (SHRs) significantly slowed
      down the age-related development of hypertension and was associated with
      increased plasma levels of nitrates, stable end-metabolites of NO. Furthermore, a
      significant improvement of coronary flow and a significant reduction of
      endothelial dysfunction were observed in SHRs submitted to chronic administration
      of VA694. In conclusion, VA694 is a promising COX2-inhibiting hybrid drug,
      showing NO releasing properties which may mitigate the CV deleterious effects
      associated with the COX2-inhibition. 

PMID- 24083951
TI  - Vitamin D deficiency is associated with pulmonary exacerbations in children with
      cystic fibrosis.
AB  - RATIONALE: Recent literature suggests vitamin D has an effect on lung function
      and on the lung's ability to fight infection, both important in the cystic
      fibrosis (CF) population as predictors of morbidity and mortality. OBJECTIVES:
      Our study assessed associations between vitamin D and % predicted lung function,
      pulmonary exacerbations, and first Pseudomonas aeruginosa infection in children
      with CF. We hypothesized that children with CF who have 25-hydroxy vitamin D (25
      OHD) levels less than 30 MUg/L would have lower % predicted lung function and
      more pulmonary exacerbations than those with 25-OHD greater than or equal to 30
      MUg/L. METHODS: This retrospective longitudinal study of 130 children aged 6 to
      18 years between 2000 and 2012 examined 25-OHD levels classed in three vitamin D
      groups: sufficient (>=30 MUg/L), insufficient (20-29 MUg/L), and deficient (<20
      MUg/L). Longitudinal models followed individuals' changing vitamin D groups over
      time to compare numbers of pulmonary exacerbations (defined by hospitalization),
      incidence of first P. aeruginosa infection, and % predicted lung function. Cross
      sectional comparisons between vitamin D groups were performed at ages 8, 12, and
      16 years. MEASUREMENTS AND MAIN RESULTS: The prevalence of vitamin D deficiency
      and insufficiency increased slowly through adolescence. The rate of exacerbations
      for the deficient vitamin D group, aged 15 to 18 years, was 13.1 per 10 patient
      years, significantly higher than 4.3 per 10 patient-years for the insufficient
      and sufficient vitamin D groups (P < 0.05), which were not significantly
      different There were no differences between vitamin D groups in pulmonary
      function or incidence of first P. aeruginosa infection, which was about 2 per 10
      patient-years. CONCLUSIONS: Higher 25-OHD levels in children with CF were
      associated with lower rates of pulmonary exacerbations and, in adolescents,
      higher FEV1.

PMID- 24083952
TI  - A preoperative nomogram for the prediction of ipsilateral central compartment
      lymph node metastases in papillary thyroid cancer.
AB  - BACKGROUND: Central compartment lymph node metastases in papillary thyroid
      carcinoma (PTC) are difficult to detect preoperatively, and the role of routine
      or prophylactic central compartment lymph node dissection (CLND) in managing PTC
      remains controversial. The aim of this project was to create a nomogram able to
      predict the occurrence of central compartment lymph node metastasis using readily
      available preoperative clinical characteristics. METHODS: Records from patients
      undergoing total thyroidectomy and lymph node dissection for PTC in the period
      1968-2012 were analyzed. Nodal status was based on results of serial hematoxylin
      and eosin (H&E) examination. Age, sex, tumor size, tumor site, and multifocality
      were included in a multivariable logistic regression model to predict lymph node
      metastasis. A coefficient-based nomogram was developed and validated using an
      external patient cohort. RESULTS: The study population included 914 patients (80%
      females) with an average central compartment nodal yield of eight per patient.
      Central compartment lymph node metastases were present in 390 patients (42.7%).
      The variables with the strongest predictive value were age (p<0.001), male sex
      (p<0.001), increasing tumor size (p<0.001), and tumor multifocality (p<0.05). The
      nomogram had good discrimination with a concordance index of 76.4% [95%
      confidence interval 73.3-79.4], supported by an external validation point
      estimate of 61.5% [95% confidence interval 49.5-73.6]. An online calculator and
      smartphone application were developed for point of care use. CONCLUSIONS: A
      validated nomogram utilizing readily available preoperative variables has been
      developed to give a predicted probability of central lymph node metastases in
      patients presenting with PTC. This nomogram may help guide surgical decision
      making in PTC.

PMID- 24083956
TI  - Enantioselective recognition and separation of racemic 1-phenylethanol by a pair
      of 2D chiral coordination polymers.
AB  - A pair of 2D chiral coordination polymers were constructed through the self
      assembly of a chiral metal-camphor-10-sulfonate salt and a bidentate linker,
      which show selective inclusion of S and R enantiomers of 1-phenylethanol
      respectively with an enantioselectivity of 9:1. 

PMID- 24083955
TI  - Binding mechanism and synergetic effects of xanthone derivatives as
      noncompetitive alpha-glucosidase inhibitors: a theoretical and experimental
      study.
AB  - Newly emerged xanthone derivatives have attracted considerable interests as a
      novel class of potent alpha-glucosidase inhibitors. To provide insights into the
      inhibitory and binding mechanisms of xanthone-based inhibitors toward alpha
      glucosidase, we carried out experimental and theoretical studies on two typical
      xanthone derivatives, i.e., 1,3,7-trihydroxyxanthone and 1,3
      dihydroxybenzoxanthone. The results indicate that these two xanthone derivatives
      belong to noncompetitive inhibitors and induce a loss in the alpha-helix content
      of the secondary structure of alpha-glucosidase. Docking simulation revealed the
      existence of multiple binding modes, in which polyhydroxyl groups and expanded
      aromatic rings acted as two key pharmacophores to form H-bonding and pi-pi
      stacking interactions with alpha-glucosidase. The fact that 1,3,7
      tridroxyxanthone and 1,3-dihydroxybenzoxanthone exhibited significant synergetic
      inhibition to alpha-glucosidase strongly suggests that both xanthone derivatives
      simultaneously bind to the distinct noncompetitive sites of yeast's alpha
      glucosidase. On the basis of the plausible binding clues, synergetic inhibition
      can be developed to be a promising strategy to achieve enhanced inhibitory
      activities. 

PMID- 24083957
TI  - Identification of combined conjugation of nabumetone phase I metabolites with
      glucuronic acid and glycine in minipig biotransformation using coupling high
      performance liquid chromatography with electrospray ionization mass spectrometry.
AB  - High-performance liquid chromatography (HPLC) coupled with electrospray
      ionization mass spectrometry (ESI-MS) was applied for the analysis of nabumetone
      metabolites during the biotransformation in minipigs. In addition to known phase
      I metabolites, the identification of phase II metabolites was achieved on the
      basis of their full-scan mass spectra and subsequent MS(n) analysis using both
      positive-ion and negative-ion ESI mode. Some phase I metabolites are conjugated
      with both glucuronide acid and glycine, which is quite unusual type of phase II
      metabolite not presented so far for nabumetone. These metabolites were found in
      small intestine content, but they were absent in minipigs urine. 

PMID- 24083958
TI  - Identification of forced degradation products of tamsulosin using liquid
      chromatography/electrospray ionization tandem mass spectrometry.
AB  - A rapid and gradient high-performance liquid chromatography combined with
      quadrupole time-of-flight electrospray ionization tandem mass spectrometry (LC/Q
      TOF-ESI-MS/MS) method has been developed for the identification and structural
      characterization of stressed degradation products of tamsulosin. Tamsulosin, a
      selective alpha1-adrenoceptor antagonist, was subjected to forced degradation
      studies under hydrolytic (acid, base and neutral), oxidative, photolytic and
      thermal stress conditions as per ICH guidelines Q1A (R2). The drug degraded
      significantly under hydrolytic (base and neutral), thermal, oxidative and
      photolytic conditions, while it was stable to acid hydrolytic stress conditions.
      A total of twelve degradation products were formed and the chromatographic
      separation of the drug and its degradation products were achieved on a GRACE C-18
      column (250mm*4.6mm, 5MUm). All the degradants have been identified and
      characterized by LC/ESI-MS/MS and accurate mass measurements. To elucidate the
      structures of degradation products, fragmentation of the [M+H](+) ions of
      tamsulosin and its degradation products was studied by using LC-MS/MS experiments
      combined with accurate mass measurements. The product ions of all the protonated
      degradation products were compared with the product ions of protonated tamsulosin
      to assign most probable structures for the observed degradation products. 

PMID- 24083959
TI  - Regulation of corticotropin-releasing factor and urocortin 2/3 mRNA by leptin in
      hypothalamic N39 cells.
AB  - Corticotropin-releasing factor (CRF) activates the pituitary-adrenal axis during
      stress, and shows anorectic effects via CRF type 1 receptors in the hypothalamus.
      Both urocortin (Ucn) 2 and Ucn3 also act as anorectic neuropeptides via CRF type
      2 receptors. Leptin, a product of the obesity gene secreted mainly from adipose
      tissue, reduces food intake and increases energy expenditure. A possible
      interaction between leptin and CRF/Ucns has been suggested, as leptin can
      regulate expression and activation of CRF and Ucns in the hypothalamus. This
      study aimed to explore the possible function of leptin in the hypothalamus, and
      its effects in regulating CRF and Ucns. The study identified mRNA expression of
      the leptin receptor (Ob-R) and its subtypes, CRF, and Ucn2/3 in mouse
      hypothalamic N39 cells. Leptin stimulated signal transducer and activators of
      transcription type 3 (STAT3) phosphorylation, directly increased the mRNA levels
      of both CRF and Ucn2/3 in hypothalamic cells, and increased Ob-Rb mRNA levels. A
      Janus kinase inhibitor inhibited the leptin-mediated increase in STAT3
      phosphorylation, and then the increases in CRF and Ucn2/3 mRNA levels. Leptin may
      contribute to a stress response or anorectic effect via the regulation of CRF and
      Ucn2/3 in the hypothalamus. 

PMID- 24083960
TI  - Analog memristors based on thickening/thinning of Ag nanofilaments in amorphous
      manganite thin films.
AB  - We developed an analog memristor based on the thickening/thinning of Ag
      nanofilaments in amorphous La(1-x)Sr(x)MnO3 (a-LSMO) thin films. The Ag/a-LSMO/Pt
      memristor exhibited excellent pinched hysteresis loops under high-excitation
      frequency, and the areas enclosed by the pinched hysteresis loops shrank with
      increasing excitation frequency, which is a characteristic typical of a
      memristor. The memristor also showed continuously tunable synapselike resistance
      and stable endurance. The a-LSMO thin films in the memristor acted as a solid
      electrolyte for Ag(+) cations, and only the Ag/a-LSMO/Pt memristor electroformed
      with a larger current compliance easily exhibited high-frequency pinched
      hysteresis loops. On the basis of the electrochemical metallization (ECM) theory
      and electrical transport models of quantum wires and nanowires, we concluded that
      the memristance is ultimately determined by the amount of charge supplied by the
      external current. The state equations of the memristor were established, and
      charge was the state variable. This study provides a new analog memristor based
      on metal nanofilaments thickening/thinning in ECM cells, which can be extended to
      other resistive switching materials. The new memristor may enable the development
      of beyond von Neumann computers.

PMID- 24083961
TI  - Multileaf collimation cardiac shielding in breast radiotherapy: Cardiac doses are
      reduced, but at what cost?
AB  - AIMS: To measure cardiac tissue doses in left-sided breast cancer patients
      receiving supine tangential field radiotherapy with multileaf collimation (MLC)
      cardiac shielding of the heart and to assess the effect on target volume
      coverage. MATERIALS AND METHODS: Sixty-seven consecutive patients who underwent
      adjuvant radiotherapy to the left breast (n = 48) or chest wall (n = 19) in
      2009/2010 were analysed. The heart, left anterior descending coronary artery
      (LAD), whole breast and partial breast clinical target volumes (WBCTV and PBCTV)
      were outlined retrospectively (the latter only in patients who had undergone
      breast-conserving surgery [BCS]). The mean heart and LAD NTDmean and maximum LAD
      doses (LADmax) were calculated for all patients (NTDmean is a biologically
      weighted mean dose normalised to 2 Gy fractions using a standard linear quadratic
      model). Coverage of WBCTV and PBCTV by the 95% isodose was assessed (BCS patients
      only). RESULTS: The mean heart NTDmean (standard deviation) was 0.8 (0.3) Gy, the
      mean LAD NTDmean 6.7 (4.3) Gy and the mean LADmax 40.3 (10.1) Gy. Coverage of the
      WBCTV by 95% isodose was <90% in one in three patients and PBCTV coverage <95%
      (range 78-94%) in one in 10 BCS patients. CONCLUSION: The use of MLC cardiac
      shielding reduces doses to cardiac tissues at the expense of target tissue
      coverage. Formal target volume delineation in combination with an assessment of
      the likelihood of local relapse is recommended in order to aid decisions
      regarding field and MLC placement.

PMID- 24083962
TI  - The antioxidant tempol decreases acute pulmonary thromboembolism-induced
      hemolysis and nitric oxide consumption.
AB  - INTRODUCTION: Acute pulmonary thromboembolism (APT) is a critical condition
      associated with acute pulmonary hypertension. Recent studies suggest that
      oxidative stress and hemolysis contribute to APT-induced pulmonary hypertension,
      possibly as a result of increased nitric oxide (NO) consumption. We hypothesized
      that the antioxidant tempol could attenuate APT-induced hemolysis, and therefore
      attenuate APT-induced increases in plasma NO consumption. MATERIALS AND METHODS:
      APT was induced in anesthetized sheep with autologous blood clots. The
      hemodynamic effects of tempol infused at 1.0mg/kg/min 30 min after APT were
      determined. Hemodynamic measurements were carried out every 15 min. To assess
      oxidative stress, serum 8-isoprostanes levels were measured by ELISA. Plasma cell
      free hemoglobin concentrations and NO consumption by plasma samples were
      determined. An in vitro oxidative AAPH-induced hemolysis assay was used to
      further validate the in vivo effects of tempol. RESULTS: APT caused pulmonary
      hypertension, and increased pulmonary vascular resistance in proportion with the
      increases in 8-isoprostanes, plasma cell-free hemoglobin concentrations, and NO
      consumption by plasma (all P<0.05). Tempol attenuated the hemodynamic alterations
      by approximately 15-20% and blunted APT-induced increases in 8-isoprostanes, in
      cell-free hemoglobin concentrations, and the increases in NO consumption by
      plasma (P<0.05). Tempol dose-dependently attenuated AAPH-induced in vitro
      hemolysis (P<0.05). CONCLUSIONS: Our findings are consistent with the idea that
      antioxidant properties of tempol decrease APT-induced hemolysis and nitric oxide
      consumption, thus attenuating APT-induced pulmonary hypertension.

PMID- 24083963
TI  - Enhanced thrombin generation in women with a history of oral contraception
      related venous thrombosis.
AB  - INTRODUCTION: In women who suffer venous thrombosis (VT) during oral
      contraceptive (OC) use, a transient risk factor (OC) is removed during the acute
      event, while most co-existing forms of thrombophilia persist and presumably
      continue to maintain hypercoagulability. The aim of this study was to establish
      if hypercoagulability persists long after OC-related VT and if it could be
      attributed to thrombophilia. MATERIALS AND METHODS: 60 women (age 33.0 +/- 8.5
      years) were investigated 5 - 64 (median 33) months after OC-related VT (patients)
      and compared to 63 apparently healthy women (controls). All women were tested for
      thrombophilia, activated partial thromboplastin time (APTT), fibrinogen, D-dimer,
      P-selectin and C-reactive protein. Thrombin generation was measured by
      Technothrombin(r) TGA assay. Overall haemostasis potential (OHP) assay with
      overall coagulation potential (OCP) and overall fibrinolytic potential (OFP) as
      supplementary parameters were measured by repeated fibrin formation and
      degradation registration. RESULTS: In patients increased endogenous thrombin
      potential (4,205 +/- 440 nM x min vs 4,015 +/- 421 nM x min, p=0.017), increased
      OCP (22.6 +/- 4.6 Abs-sum vs 20.8 +/- 4.1 Abs-sum, p=0.025), shorter APTT (30.9
      +/- 3.8s vs 33.4 +/- 3.6s, p<0.001) and lower antithrombin activity (99, 93-105%
      vs 104, 100-109%, p<0.05) were observed. Thrombophilia was observed in 22/60
      (36%) patients and in 5/63 (7.9%, p<0.001) controls. The only significant
      difference between thrombophilic and non-thrombophilic patients was higher
      soluble P-selectin in the former subgroup (22, 20-33 MUg/L vs 17, 12-22 MUg/L,
      p=0.012). CONCLUSIONS: In women with a history of OC-related VT persistent
      hypercoagulability was observed, which, however was not augmented by the presence
      of thrombophilia.

PMID- 24083964
TI  - Comments regarding "results from craniocaudal carotid body tumor resection;
      should it be the standard surgical approach?".

PMID- 24083966
TI  - Ceramides: a potential therapeutic target in pulmonary emphysema.
AB  - BACKGROUND: The aim of this manuscript was to characterize airway ceramide
      profiles in a rodent model of elastase-induced emphysema and to examine the
      effect of pharmacological intervention directed towards ceramide metabolism.
      METHODS: Adult mice were anesthetized and treated with an intratracheal
      instillation of elastase. Lung function was measured, broncho-alveolar lavage
      fluid collected and histological and morphometrical analysis of lung tissue
      performed within 3 weeks after elastase injection, with and without
      sphingomyelinase inhibitors or serine palmitoyltransferase inhibitor. Ceramides
      in broncho-alveolar lavage (BAL) fluid were quantified by tandem mass
      spectrometry. RESULTS: BAL fluid showed a transient increase in total protein and
      IgM, and activated macrophages and neutrophils. Ceramides were transiently
      upregulated at day 2 after elastase treatment. Histology showed persistent patchy
      alveolar destruction at day 2 after elastase installation. Acid and neutral
      sphingomyelinase inhibitors had no effect on BAL ceramide levels, lung function
      or histology. Addition of a serine palmitoyltransferase inhibitor ameliorated
      lung function changes and reduced ceramides in BAL. CONCLUSIONS: Ceramides were
      increased during the acute inflammatory phase of elastase-induced lung injury.
      Since addition of a serine palmitoyltransferase inhibitor diminished the rise in
      ceramides and ameliorated lung function, ceramides likely contributed to the
      early phase of alveolar destruction and are a potential therapeutic target in the
      elastase model of lung emphysema.

PMID- 24083967
TI  - Validation of a short, qualitative food frequency questionnaire in French adults
      participating in the MONA LISA-NUT study 2005-2007.
AB  - BACKGROUND: Food frequency questionnaires (FFQs) are often used to evaluate
      individuals' food intakes in epidemiologic studies because of their simplicity
      and low cost. OBJECTIVE: To assess the validity of a short (24 items),
      qualitative FFQ used in the MONA LISA-NUT study. DESIGN: Cross-sectional study of
      a representative sample in three French counties. PARTICIPANTS/SETTING: The
      sample included 2,630 participants aged 35 to 65 years from the MONA LISA-NUT
      study. MAIN OUTCOME MEASURES: Food consumption was measured with the FFQ and via
      food records for 3 consecutive days. Plasma fatty acids were measured from a
      subset of participants. STATISTICAL ANALYSES PERFORMED: The FFQ items' validity
      was assessed by calculating crude and deattenuated Pearson correlation
      coefficients between frequencies reported by the FFQ and average weights reported
      by the food records. Furthermore, the validity of some items of the FFQ measuring
      the consumption of fatty foods was assessed by calculating Pearson correlation
      coefficients between frequencies of consumption of these foods and dosages of the
      corresponding plasma fatty acids: fish and eicosapentaenoic acid (EPA) and
      docosahexaenoic acid (DHA), olive oil and oleic acid, margarine and elaidic acid,
      and dairy products and pentadecanoic and heptadecanoic acids. RESULTS: The mean
      of the deattenuated Pearson correlation coefficients for all items was 0.46, with
      values ranging from 0.22 (fried food) to 0.77 (breakfast cereal). The correlation
      coefficient was <= 0.4 for one third of the 24 items. Moderate correlations were
      found between fish and EPA/DHA (EPA: r=0.43, 95% CI 0.33 to 0.51; DHA: r=0.39,
      95% CI 0.30 to 0.47), but not for other food items. CONCLUSIONS: One third of the
      24 items in the short, qualitative FFQ evaluated here were not sufficiently
      valid. However, for the food groups most commonly studied in the literature, this
      FFQ had the same degree of validity as other questionnaires designed to classify
      subjects according to their level of intake.

PMID- 24083968
TI  - Mitochondrial genome of Protobothrops xiangchengsis (Squamata: Viperidae:
      Crotalinae).
AB  - Protobothrops xiangchengsis is the endangered snake which is only distributed in
      China. We determined the complete mitochondrial genome of P. xiangchengsis (HB
      px20100722). The circle genome with the 17,240 bp total length contained 13
      protein-coding genes, 22 transfer RNA genes, 2 ribosomal RNA genes and 2 control
      regions. Overall base composition of the complete mtDNA was 33.16% A, 25.16% T,
      29.17% C and 12.51% G. All the genes in P. xiangchengsis were distributed on the
      H-strand, except for the ND6 subunit gene and eight tRNA genes which were encoded
      on the L-strand.

PMID- 24083969
TI  - The complete mitochondrial genome of Pseudobagrus albomarginatus Rendhal:
      sequencing and analysis.
AB  - In this study, the total mitochondrial genome sequence of Pseudobagrus
      albomarginatus Rendhal was firstly sequenced and determined. The total genome is
      16,533 bp in length. It consists of 13 protein-coding genes, 22 tRNA genes, two
      rRNA genes and two non-coding regions. The data presented herein would facilitate
      further investigations of phylogenetic relationships within Bagridae catfishes.

PMID- 24083970
TI  - Mitochondrial genome of the Naemorhedus griseus (Bovidae: Naemorhedus).
AB  - Naemorhedus griseus, vulnerable animal, has undergone a significant decline.
      Here, we analyzed the complete mitochondrial genome (16,554 bp in length) to
      supplement the database of N. griseus. The complete mtDNA of N. griseus contained
      37 genes (13 protein-coding genes, two rRNA genes and 22 tRNA genes) and a non
      coding region (D-loop). Additionally, a rep-origin (32 bp) exists which located
      between tRNA(Asn) and tRNA(Cys). 

PMID- 24083971
TI  - Complete mitochondrial genome of the Antarctic soft-shelled clam, Laternula
      elliptica (Bivalvia; Laternulidae).
AB  - The complete mitogenome of the Antarctic soft-shelled clam, Laternula elliptica
      was determined to be 14,622 bp in length, and to contain 13 protein coding genes
      (PCGs), 22 tRNA genes, and large (rrnL) and small (rrnS) rRNA genes. Its total A
      + T content is 55.09%. The L. elliptica mitogenome is the smallest one among
      those of bivalvia, due to the existence of relatively small intergenic non-coding
      sequences. All genes are transcribed from the light-strand as a template like
      bivalve taxa except Unionoidea.

PMID- 24083972
TI  - Complete mitochondrial genome of Dendronephthya putteri (Octocorallia,
      Alcyonacea) and useful candidate for developing DNA barcode markers of
      Dendronephthya species.
AB  - The mitochondrial genome of Dendronephthya putteri (Octocorallia, Alcyonacea)
      which is an endangered species was completely sequenced. It is 18,853 bp in
      length and identical to those of Dendronephthya species in its gene arrangement
      and genome organization. Nucleotide sequence comparison of the mitochondrial
      genomes of the two D. putteri individuals obtained from this study and the
      previously reported one (GenBank accession number JQ290079) showed that they are
      identical perfectly. We found useful candidate for DNA barcode markers for D.
      putteri species identification.

PMID- 24083973
TI  - Identification of sequence polymorphisms in the D-loop region of mitochondrial
      DNA as risk biomarkers for malignant fibrous histiocytoma.
AB  - Single nucleotide polymorphisms (SNPs) in the mitochondrial DNA Displacement-loop
      (D-loop) region particularly in a highly polymorphic homopolymeric C stretch
      named D310 have been reported to be associated with cancer risk in several types
      of cancer. In order to evaluate the frequency of D-loop SNPs in a large series of
      malignant fibrous histiocytoma (MFH) and establish correlations with cancer risk,
      we sequenced the D-loop of 92 MFH patients and analyzed their use as predictive
      biomarkers for MFH risk. The minor alleles of nucleotides 73G, 151T were
      associated with an increased risk for MFH patients, whereas the alleles of
      nucleotides 16,298C, 152C, and insertion of C at the site 315 (located within the
      D310) were associated with a decreased risk for MFH patients. These results
      suggest that SNPs in the mitochondrial D-loop should be considered as a biomarker
      which may be useful for the early detection of MFH in individuals at risk of this
      cancer. 

PMID- 24083974
TI  - The complete mitochondrial genome of Pseudobagrus ondon Shaw.
AB  - In this study, the total mitochondrial genome sequence of Pseudobagrus ondon Shaw
      was firstly sequenced and determined. The total genome is 16,543 bp in length. It
      consists of 13 protein-coding genes, 22 tRNA genes, 2 rRNA genes and 2 non-coding
      regions. These results provide useful data to the natural resources conservation
      and systematics analysis of P. ondon Shaw.

PMID- 24083975
TI  - Rearrangement of the nad1 gene in Pristaulacus compressus (Spinola) (Hymenoptera:
      Evanioidea: Aulacidae) mitochondrial genome.
AB  - The mitochondrial genome of the Pristaulacus compressus (Spinola, 1808)
      (Hymenoptera: Aulacidae) (GenBank accession No. KF500406) is reported in this
      study. This is the first sequenced mitochondrial genome from the family Aulacidae
      of the order Hymenoptera. The length of this mitochondrial genome is 15,563 bp
      with an A + T content of 84%, including 13 protein-coding, 2 rRNA and 22 tRNA
      gene, and an A + T-rich region (Table 1). Three tRNA and one protein-coding genes
      were rearranged in the P. compressus mitochondrial genome, in which, the trnY was
      inverted, while the trnQ was shuffled to the downstream of tRNA cluster trnI-trnQ
      trnM. The trnS1 was translocated to the downstream of the A + T-rich region
      together with the protein-coding gene nad1. The gene arrangement pattern of this
      mitochondrial genome is new to the Hymenoptera. All protein-coding genes start
      with ATN start codon. Ten protein-coding genes stop with termination codon TAA,
      whereas one protein-coding gene uses incomplete stop codon TA and two use T. The
      A + T-region is located between rrnS and trnS1 with a length of 780 bp.

PMID- 24083976
TI  - Computational modeling of protein-RNA complex structures.
AB  - Protein-RNA interactions play fundamental roles in many biological processes,
      such as regulation of gene expression, RNA splicing, and protein synthesis. The
      understanding of these processes improves as new structures of protein-RNA
      complexes are solved and the molecular details of interactions analyzed. However,
      experimental determination of protein-RNA complex structures by high-resolution
      methods is tedious and difficult. Therefore, studies on protein-RNA recognition
      and complex formation present major technical challenges for macromolecular
      structural biology. Alternatively, protein-RNA interactions can be predicted by
      computational methods. Although less accurate than experimental measurements,
      theoretical models of macromolecular structures can be sufficiently accurate to
      prompt functional hypotheses and guide e.g. identification of important amino
      acid or nucleotide residues. In this article we present an overview of strategies
      and methods for computational modeling of protein-RNA complexes, including
      software developed in our laboratory, and illustrate it with practical examples
      of structural predictions. 

PMID- 24083977
TI  - Dyadic relational resources and role strain in family caregivers of persons
      living with dementia at home: A cross-sectional survey.
AB  - BACKGROUND: Family caregivers of older persons with dementia face negative
      impacts such as heightened role strain due to care receivers' incremental loss of
      cognitive function. Dyadic relational resources were found to protect caregivers
      against negative caregiving outcomes while caring for cancer patients, but had
      not been explored in caregivers of patients with dementia. OBJECTIVE: To explore
      whether the impact of caregiving demand/care receivers' cognitive functioning on
      caregiver role strain is moderated by dyadic relational resources. DESIGN: Cross
      sectional correlational survey. SETTING: The neurological clinics of a 3700-bed
      medical centre, neurological ward, and day care centre affiliated with a regional
      hospital in northern Taiwan. PARTICIPANTS: A convenience sample of 219 family
      caregivers and care receivers with dementia was enrolled, with 197 (90%)
      completing the study questionnaires. METHOD: Data were collected from family
      caregivers' self-completed questionnaires from December 2010 to November 2011. We
      examined the moderating effects of caregiving demand/care receiver dementia
      severity and dyadic relational resources (mutuality, preparedness and
      predictability) on caregiving outcome (role strain) using hierarchical multiple
      regression analyses. Moderating effects were examined according to two- and three
      way interaction terms in the regressions. We also explored the simple effect of
      each independent variable on role strain. RESULTS: The dyadic relational
      resources of mutuality and preparedness moderated the effects of caregiving
      demand on caregivers' role strain. That is, a high level of mutuality and
      preparedness protected caregivers from high levels of role strain, even when
      caregiving demand was high. Another important factor was a high level of
      predictability, which tended to decrease role strain. Finally, the association
      between care receiver cognitive functioning and caregiver role strain was
      influenced by the level of mutuality between caregiver and care receiver. More
      specifically, high levels of mutuality diminished role strain in caregivers of
      patients with mild dementia. CONCLUSIONS: Dyadic relational resources may
      moderate the effects of role strain. These findings suggest that these dyadic
      relational resources should be enhanced for family caregivers of patients with
      dementia to ease their caregiving role strain.

PMID- 24083978
TI  - Estrogen-related receptor gamma induces cardiac hypertrophy by activating GATA4.
AB  - Estrogen-related receptor gamma (ERRgamma) is an orphan nuclear receptor that has
      biological roles mainly in metabolism and that controls metabolic switching in
      perinatal heart. In adult heart diseases, however, the functional roles of
      ERRgamma have not yet been elucidated. In the present study, we aimed to
      characterize the role of ERRgamma in cardiac hypertrophy. The functional roles of
      ERRgamma in the development of cardiac hypertrophy were examined in primary
      cultured cardiomyocytes and in animal models. ERRgamma expression was increased
      in hearts from human hypertrophic cardiomyopathy patients and in both cellular
      and animal models of cardiac hypertrophy. Transgenic overexpression in mouse
      heart as well as forced expression of ERRgamma in cardiomyocytes induced
      hypertrophic phenotypes. Knock-down of ERRgamma blocked agonist-induced
      hypertrophic phenotypes. ERRgamma bound directly to the proximal ERR-responsive
      element in the GATA4 promoter in a sequence-specific manner and thereby induced
      transcription. ERRgamma-induced hypertrophy was blocked by inhibition of GATA4.
      GSK-5182, an inverse agonist of ERRgamma, completely blocked cardiac hypertrophy
      in cardiomyocytes. It also prevented aortic banding-induced cardiac hypertrophy
      and fibrosis in mouse heart. These findings demonstrate a novel ERRgamma/GATA4
      signal cascade in the development of cardiac hypertrophy and suggest GSK-5182 as
      a possible therapeutic. 

PMID- 24083979
TI  - MicroRNA transcriptome profiling in cardiac tissue of hypertrophic cardiomyopathy
      patients with MYBPC3 mutations.
AB  - Hypertrophic cardiomyopathy (HCM) is predominantly caused by mutations in genes
      encoding sarcomeric proteins. One of the most frequent affected genes is MYBPC3,
      which encodes the thick filament protein cardiac myosin binding protein C.
      Despite the prevalence of HCM, disease pathology and clinical outcome of
      sarcomeric mutations are largely unknown. We hypothesized that microRNAs (miRNAs)
      could play a role in the disease process. To determine which miRNAs were changed
      in expression, miRNA arrays were performed on heart tissue from HCM patients with
      a MYBPC3 mutation (n=6) and compared with hearts of non-failing donors (n=6). 532
      out of 664 analyzed miRNAs were expressed in at least one heart sample. 13 miRNAs
      were differentially expressed in HCM compared with donors (at p<0.01, fold change
      >= 2). The genomic context of these differentially expressed miRNAs revealed that
      miR-204 (fold change 2.4 in HCM vs. donor) was located in an intron of the TRPM3
      gene, encoding an aspecific cation channel involved in calcium entry. RT-PCR
      analysis revealed a trend towards TRPM3 upregulation in HCM compared with donor
      myocardium (fold change 2.3, p=0.078). In silico identification of mRNA targets
      of differentially expressed miRNAs showed a large proportion of genes involved in
      cardiac hypertrophy and cardiac beta-adrenergic receptor signaling and we showed
      reduced phosphorylation of cardiac troponin I in the HCM myocardium when compared
      with donor. HCM patients with MYBPC3 mutations have a specific miRNA expression
      profile. Downstream mRNA targets reveal possible involvement in cardiac signaling
      pathways.

PMID- 24083980
TI  - Time-resolved infrared studies of a trimethylphosphine model derivative of [FeFe]
      hydrogenase.
AB  - Model compounds that structurally mimic the hydrogen-producing active site of
      [FeFe]-hydrogenases have been studied to explore potential ground-state
      electronic structure effects on reaction mechanisms compared to hexacarbonyl
      derivatives. The time-dependent behavior of Fe2(MU-S2C3H6)(CO)4(PMe)2 (A) in room
      temperature n-heptane and acetonitrile solutions was examined using various
      ultrafast UV and visible excitation pulses with broadband IR-probe spectroscopy
      of the carbonyl (CO) stretching region. Ground- and excited-state electronic and
      CO-stretching mode vibrational properties of the possible isomers of A were also
      examined using density functional theory (DFT) computations. In n-heptane, 355
      and 532 nm excitation resulted in short-lived (135 +/- 74 ps) bands assigned to
      excited-state, CO-loss photoproducts. These bands decay away, forming new long
      lived absorptions that are likely a mixture of isomers of both three-CO and four
      CO ground-state isomers. These new bands grow in with a time scale of 214 +/- 119
      ps and persist for more than 100 ns. In acetonitrile, similar results are seen
      with a 532 nm pump, but the 355 nm data lack evidence of the longer-lived bands.
      In either solvent, the 266 nm pump data seem to also lack longer-lived bands, but
      the intensities are significantly lower in this data, making firm conclusions
      more difficult. We suggest that these wavelength-dependent excitation dynamics
      significantly alter potential mechanisms and efficiencies for light-driven
      catalysis. 

PMID- 24083981
TI  - Magnesium and calcium complexes containing biphenyl-based tridentate
      iminophenolate ligands for ring-opening polymerization of rac-lactide.
AB  - A series of racemic 2-[(2'-methoxybiphenyl-2-ylimino)methyl]-4-R(2)-6-R(1)
      phenols (L(1)H-L(8)H) were reacted with {Mg[N(SiMe3)2]2}2 and Ca[N(SiMe3)2]2.2THF
      (THF = tetrahydrofuran), respectively, to provide nine heteroleptic magnesium
      complexes L(1-8)MgN(SiMe3)2 [R(1) = (i)Pr, R(2) = H (1a); R(1) = (t)Bu, R(2) = Me
      (2a and 2a.THF); R(1) = R(2) = (t)Bu (3a); R(1) = R(2) = CMe2Ph (4a); R(1) =
      CPh3, R(2) = (t)Bu (5a); R(1) = 1-piperidinylmethyl, R(2) = (t)Bu (6a); R(1) =
      Cl, R(2) = (t)Bu (7a); R(1) = Br, R(2) = (t)Bu (8a)], two homoleptic calcium
      complexes (L(2,5))2Ca (2b and 5b), and one heteroleptic calcium complex
      [(L(4))CaN(SiMe3)2.THF] (4b), which have been fully characterized. In the solid
      state, magnesium complexes 2a and 6a are isostructural, and each possesses a
      monomeric structure, while magnesium complexes 7a and 8a are dimeric, where the
      two metal centers are bridged by two phenolate oxygen atoms of the ligands. The
      coordination geometry around the magnesium center in these complexes can be best
      described as a distorted tetrahedral geometry. Although bearing the same
      iminophenoloate ligand, the molecular structures of complexes 2a and 2a.THF are
      different from each other. In complex 2a.THF, the coordination of one molecule of
      THF to the magnesium atom leads to dissociation of the methoxy group of the
      ligand from the metal center. The homoleptic calcium complex 2b has a six
      coordinate metal core ligated by all six donor atoms of two iminophenolate
      ligands. The heteroleptic magnesium complexes 1a-8a and calcium complex 4b proved
      to be efficient initiators for the ring-opening polymerization of rac-lactide at
      ambient temperature in THF or at 70  degrees C in toluene, and the
      polymerizations were better controlled in the presence of 2-propanol. The
      introduction of a bulky ortho substituent on the phenoxy unit of the ligand
      resulted in an increase of the catalytic activity of the corresponding metal
      complex. Microstructure analysis of the resultant poly(rac-lactide) samples via
      homonuclear-decoupled (1)H NMR spectroscopy revealed Pr values ranging from 0.60
      to 0.81, which closely depended on the employed catalyst and polymerization
      conditions. 

PMID- 24083982
TI  - The nursing home effect: a case study of residents with potential dementia and
      emergency department visits.
AB  - OBJECTIVES: The burden of potential dementia cases without formal diagnosis on
      the health care system is almost unknown. This study examined the impact of
      potential dementia without formal diagnosis on the rate of visits to hospital
      emergency department (ED) of nursing home (NH) residents. DESIGN: Cross-sectional
      study. SETTING: NHs (175) located in France. PARTICIPANTS: A total of 5684
      subjects who were living in the NH for at least 1 year. MEASUREMENTS: Information
      on NHs' characteristics and on NH residents' health was recorded by NH staff.
      Participants were divided in 3 groups according to their dementia status:
      diagnosed dementia, potential dementia without formal diagnosis, and nondementia.
      The outcome measure was a binary variable: ED visits in the last 12 months (yes
      vs no). A mixed-effects logistic regression was performed on ED visits accounting
      for the random effects of living in a particular NH. RESULTS: From the 5684
      participants, 1036 had been seen in the ED. Adjusted odds ratio (AOR) showed that
      having a potential dementia without formal diagnosis, compared with a diagnosed
      dementia, was associated with an increased probability of ED visits (AOR = 1.25,
      95% confidence interval: 0.99-1.59, P = .061); however, when a random NH effect
      was entered into the model, the association between potential dementia without
      formal diagnosis and ED visits disappeared (AOR = 1.22, 95% confidence interval:
      0.95-1.57, P = .11). CONCLUSION: The association of potential dementia without
      formal diagnosis with ED visits varies across NHs. This intra-NH aspect (eg,
      organization and care habits) should be taken into account when examining the
      rates of hospitalization and possibly the use of health care services in general
      among NH residents.

PMID- 24083983
TI  - Drug rescue distinguishes between different structural models of human P
      glycoprotein.
AB  - There is no high-resolution crystal structure of the human P-glycoprotein (P-gp)
      drug pump. Homology models of human P-gp based on the crystal structures of mouse
      or Caenorhabditis elegans P-gps show large differences in the orientation of
      transmembrane segment 5 (TM5). TM5 is one of the most important transmembrane
      segments involved in drug-substrate interactions. Drug rescue of P-gp processing
      mutants containing an arginine at each position in TM5 was used to identify
      positions facing the lipid or internal aqueous chamber. Only the model based on
      the C. elegans P-gp structure was compatible with the drug rescue results. 

PMID- 24083984
TI  - Anti-parietal cell antibodies and pernicious anemia in patients with type 1
      diabetes mellitus and multiethnic background.
AB  - Anti-parietal cell (APC) antibodies and pernicious anemia (PA) were evaluated in
      patients with type 1 diabetes (n=75) and in controls. A higher frequency of APC
      (13.3%) and PA (4%) was found in cases than in controls (p=0.003), associated
      with other autoimmune diseases (p=0.003), but not with insulin or PTPN22
      polymorphisms.

PMID- 24083985
TI  - Serotonin transporter and integrin beta 3 genes interact to modulate serotonin
      uptake in mouse brain.
AB  - Dysfunctions in serotonin (5-hydroxytryptamine, 5-HT) systems have been
      associated with several psychiatric illnesses, including anxiety, depression,
      obsessive-compulsive disorders and autism spectrum disorders. Convergent evidence
      from genetic analyses of human subjects has implicated the integrin beta3 subunit
      gene (ITGB3) as a modulator of serotonergic systems via genetic interactions with
      the 5-HT transporter gene (SLC6A4, SERT). While genetic interactions may result
      from contributions of each gene at several levels, we hypothesize that ITGB3
      modulates the 5-HT system at the level of the synapse, through the actions of
      integrin alphavbeta3. Here we utilized a genetic approach in mouse models to
      examine Itgb3 contributions to SERT function both in the context of normal and
      reduced SERT expression. As integrin alphavbeta3 is expressed in postsynaptic
      membranes, we isolated synaptoneurosomes, which maintain intact pre- and post
      synaptic associations. Citalopram binding revealed significant Slc6a4-driven
      reductions in SERT expression in midbrain synapses, whereas no significant
      changes were observed in hippocampal or cortical projections. Expecting
      corresponding changes to SERT function, we also measured 5-HT uptake activity in
      synaptoneurosomal preparations. Itgb3 single heterozygous mice displayed
      significant reductions in 5-HT Vmax, with no changes in Km, in midbrain
      preparations. However, in the presence of both Itgb3 and Slc6a4 heterozygozity, 5
      HT uptake was similar to wild-type levels, revealing a significant Slc6a4 by
      Itgb3 genetic interaction in the midbrain. Similar findings were observed in
      cortical preparations, whereas in the hippocampus, most Vmax changes were driven
      solely by Slc6a4. Our findings provide evidence that integrin alphavbeta3 is
      involved in the regulation of serotonergic systems in some, but not all 5-HT
      synapses, revealing novel contributions to synaptic specificity within the
      central nervous system. 

PMID- 24083986
TI  - Licorice-derived dehydroglyasperin C increases MKP-1 expression and suppresses
      inflammation-mediated neurodegeneration.
AB  - Recent studies have demonstrated that microglial hyperactivation-mediated
      neuroinflammation is involved in the pathogenesis of several neurodegenerative
      diseases. Thus, inhibiting microglial production of the neurotoxic mediator tumor
      necrosis factor-alpha (TNF-alpha) is considered a promising strategy to protect
      against neurodegeneration. Here, we investigated the inhibitory effect of
      licorice-derived dehydroglyasperin C (DGC) on lipopolysaccharide (LPS)-induced
      TNF-alpha production and inflammation-mediated neurodegeneration. We found that
      DGC pre-treatment attenuated TNF-alpha production in response to LPS stimulation
      of BV-2 microglia. DGC pre-treatment attenuated LPS-induced inhibitor of kappaB
      alpha (IkappaB-alpha) and p65 phosphorylation and decreased the DNA binding
      activity of nuclear factor-kappaB (NF-kappaB). DGC pre-treatment also inhibited
      LPS-mediated phosphorylation of p38 mitogen-activated protein kinases (MAPKs) and
      extracellular signal-regulated kinase (ERK). Interestingly, DGC treatment of BV-2
      microglia significantly increased MAPK phosphatase 1 (MKP-1) mRNA and protein
      expression, which is a phosphatase of p38 MAPK and ERK, suggesting that the DGC
      mediated increase in MKP-1 expression might inhibit LPS-induced MAPKs and NF
      kappaB activation and further TNF-alpha production. We also found that LPS
      mediated microglial neurotoxicity can be attenuated by DGC. The addition of
      conditioned media (CM) from DGC- and LPS-treated microglia to neurons helped
      maintain healthy cell body and neurite morphology and increased the number of
      microtubule-associated protein 2-positive cells and the level of synaptophysin
      compared to treatment with CM from LPS-treated microglia. Taken together, these
      data suggest that DGC isolated from licorice may inhibit microglia
      hyperactivation by increasing MKP-1 expression and acting as a potent anti
      neurodegenerative agent. 

PMID- 24083987
TI  - Mechanism of action of salsolinol on tyrosine hydroxylase.
AB  - Tyrosine hydroxylase (TH) is the first and rate-limiting enzyme in dopamine
      synthesis. Dopamine regulates TH as an end-product inhibitor through its binding
      to a high and low affinity site, the former being abolished by Ser40
      phosphorylation only, and the latter able to bind and dissociate according to
      intracellular dopamine levels. Here, we have investigated TH inhibition by a
      dopamine metabolite found in dopaminergic brain regions, salsolinol (SAL). SAL is
      known to decrease dopamine in the nigrostriatal pathway and mediobasal
      hypothalamus, and to also decrease plasma catecholamines in rat stress models,
      however a target and mechanism for the effects of SAL have not been found. We
      found that SAL inhibits TH activity in the nanomolar range in vitro, by binding
      to both the high and low affinity dopamine binding sites. SAL produces the same
      level of inhibition as dopamine when TH is non-phosphorylated. However, it
      produces 3.7-fold greater inhibition of Ser40-phosphorylated TH compared to
      dopamine by competing more strongly with tetrahydrobiopterin, the cofactor of
      this enzymatic reaction. SAL's potent inhibition of phosphorylated TH would
      prevent TH from being fully activated to synthesise dopamine. 

PMID- 24083990
TI  - Health related quality of life in parents of six to eight year old children with
      Down syndrome.
AB  - Raising a child with Down syndrome (DS) has been found to be associated with
      lowered health related quality of life (HRQoL) in the domains cognitive
      functioning, social functioning, daily activities and vitality. We aimed to
      explore which socio-demographics, child functioning and psychosocial variables
      were related to these HRQoL domains in parents of children with DS. Parents of 98
      children with DS completed the TNO-AZL adult quality of life questionnaire
      (TAAQOL) and a questionnaire assessing socio-demographic, child functioning and
      psychosocial predictors. Using multiple linear regression analyses for each
      category of predictors, we selected relevant predictors for the final models. The
      final multiple linear regression models revealed that cognitive functioning was
      best predicted by the sleep of the child (beta=.29, p<.01) and by the parent
      having given up a hobby (beta=-.29, p<.01), social functioning by the quality of
      the partner relation (beta=.34, p<.001), daily activities by the parent having to
      care for an ill friend or family member (beta=-.31, p<.01), and vitality by the
      parent having enough personal time (beta=.32, p<.01). Overall, psychosocial
      variables rather than socio-demographics or child functioning showed most
      consistent and powerful relations to the HRQoL domains of cognitive functioning,
      social functioning, daily activities and vitality. These psychosocial variables
      mainly related to social support and time pressure. Systematic screening of
      parents to detect problems timely, and interventions targeting the supportive
      network and the demands in time are recommended. 

PMID- 24083988
TI  - Axon degeneration is key component of neuronal death in amyloid-beta toxicity.
AB  - Depending upon the stimulus, neuronal cell death can either be triggered from the
      cell body (soma) or the axon. We investigated the origin of the degeneration
      signal in amyloid beta (Abeta) induced neuronal cell death in cultured in vitro
      hippocampal neurons. We discovered that Abeta1-42 toxicity-induced axon
      degeneration precedes cell death in hippocampal neurons. Overexpression of Bcl-xl
      inhibited both axonal and cell body degeneration in the Abeta-42 treated neurons.
      Nicotinamide mononucleotide adenylyltransferase 1 (Nmnat1) blocks axon
      degeneration in a variety of paradigms, but it cannot block neuronal cell body
      death. Therefore, if the neuronal death signals in Abeta1-42 toxicity originate
      from degenerating axons, we should be able to block neuronal death by inhibiting
      axon degeneration. To explore this possibility we over-expressed Nmnat1 in
      hippocampal neurons. We found that inhibition of axon degeneration in Abeta1-42
      treated neurons prevented neuronal cell death. Thus, we conclude that axon
      degeneration is the key component of Abeta1-42 induced neuronal degeneration, and
      therapies targeting axonal protection can be important in finding a treatment for
      Alzheimer's disease. 

PMID- 24083989
TI  - Apelin-36, a potent peptide, protects against ischemic brain injury by activating
      the PI3K/Akt pathway.
AB  - Apelin is an endogenous ligand of G protein-coupled receptor-apelin and
      angiotensin-1-like receptor (APJ). The biological effects of apelin-APJ system
      are reported in multiple systems including cardiovascular, endocrinal, and
      gastrointestinal system. Previous studies had shown that apelin-13 is a potential
      protective agent on cardiac ischemia; however, the role of apelin in the central
      nervous system remained unknown. In this study, we investigated therapeutic
      effects of apelin-36, a long form of apelin, in ischemic brain injury models. We
      found that apelin-36 reduced cerebral infarct volume in the middle cerebral
      artery occlusion (MCAO) model and the neonatal hypoxic/ischemic (H/I) injury
      model. Apelin-36 improved neurological deficits in the MCAO model and promoted
      long-term functional recovery after H/I brain injury. We further explored the
      protective mechanisms of apelin-36 on H/I brain injury. We clearly demonstrated
      that apelin-36 significantly reduced the levels of cleaved caspase-3 and Bax, two
      well-established apoptotic markers after H/I injury, indicating the anti
      apoptotic activity of apelin-36 in ischemic injury. Since apelin-36 increased the
      level of phosphorylated Akt after H/I injury, we treated neonates with a specific
      PI3K inhibitor LY294002. We found that LY294002 decreased the phosphorylated Akt
      level and attenuated protective effects of apelin-36 on apoptosis. These
      suggested that the PI3K/Akt pathway was at least in part involved in the anti
      apoptotic mechanisms of apelin-36. Our findings demonstrated that apelin-36 was a
      promising therapeutic agent on the treatment of ischemic brain injury. 

PMID- 24083991
TI  - Iron overload induces changes of pancreatic and duodenal divalent metal
      transporter 1 and prohepcidin expression in mice.
AB  - It is well known that the iron content of the body is tightly regulated. Iron
      excess induces adaptive changes that are differentially regulated in each tissue.
      The pancreas is particularly susceptible to iron-related disorders. We studied
      the expression and regulation of key iron proteins in the pancreas, duodenum and
      liver, using an animal model of iron overload (female CF1 mice injected i.p. with
      iron saccharate, colloidal iron form). Divalent metal transporter 1, prohepcidin
      and ferritin (pancreas, duodenum, liver) were assessed by immunohistochemistry;
      divalent metal transporter 1 (pancreas, duodenum) by Western blot. In the iron
      overloaded mice, prohepcidin expression increased in islets of Langerhans and
      hepatocytes, and divalent metal transporter 1 expression decreased in cells of
      islets and in enterocytes. In the iron overloaded mice, ferritin expression
      decreased in islets of Langerhans and increased in acinar cells; hemosiderin was
      localized in connective tissue cells. The inverse relationship between divalent
      metal transporter 1 and prohepcidin may indicate a negative regulation by
      hepcidin, and hence reduction of iron stores in islets of Langerhans. Our data
      showed that in iron overloaded mice model, induced by colloidal iron form, a
      coordinated expression of key iron proteins in the pancreas, duodenum and liver
      may occur. Further research will be necessary to determine the adaptive responses
      induced by iron in the pancreas. 

PMID- 24083992
TI  - Underwater superoleophilic to superoleophobic wetting control on the
      nanostructured copper substrates.
AB  - Surfaces with controlled underwater oil wettability would offer great promise in
      the design and fabrication of novel materials for advanced applications. Herein,
      we propose a new approach based on self-assembly of mixed thiols (containing both
      HS(CH2)9CH3 and HS(CH2)11OH) on nanostructured copper substrates for the
      fabrication of surfaces with controlled underwater oil wettability. By simply
      changing the concentration of HS(CH2)11OH in the solution, surfaces with
      controlled oil wettability from the underwater superoleophilicity to
      superoleophobicity can be achieved. The tunable effect can be due to the
      synergistic effect of the surface chemistry variation and the nanostructures on
      the surfaces. Noticeably, the amplified effect of the nanostructures can provide
      better control of the underwater oil wettability between the two extremes:
      superoleophilicity and superoleophobicity. Moreover, we also extended the
      strategy to the copper mesh substrates and realized the selective oil/water
      separation on the as-prepared copper mesh films. This report offers a flexible
      approach of fabricating surfaces with controlled oil wettability, which can be
      further applied to other ordinary materials, and open up new perspectives in
      manipulation of the surface oil wettability in water. 

PMID- 24083993
TI  - Proliferative phenotype of pulmonary microvascular endothelial cells plays a
      critical role in the overexpression of CTGF in the bleomycin-injured rat.
AB  - The pathogenesis of idiopathic pulmonary fibrosis (IPF) is not very clear, with
      evidence for the involvement of both inflammation and aberrant vascular
      remodeling (associated with angiogenesis). Pulmonary microvascular endothelial
      cells (PMVECs), which play a major role in inflammation, secrete cytokines that
      promote the transformation and collagen synthesis of fibroblasts. Moreover,
      angiogenesis is characterized by PMVEC proliferation. The main aim of this study
      was to confirm the role of PMVECs in pulmonary fibrosis. Accordingly, we observed
      the functional changes in PMVECs in bleomycin (BLM)-treated rats (pulmonary
      fibrosis model) in vivo, and compared them with those of rats with pneumonia. The
      proliferation phenotype and intracellular ionized calcium concentration
      ([Ca(2+)]i) of PMVECs from BLM-treated rats were also investigated. The
      functioning of PMVECs was abnormal in BLM-injured rats, particularly with regard
      to their proliferation and secretion of connective tissue growth factor (CTGF).
      [Ca(2+)]i was increased in the proliferated PMVECs from BLM-treated rats. The
      findings suggest that dysfunction of PMVECs characterized by overexpression of
      CTGF is critical in rat pulmonary injury induced by BLM, and is probably related
      with the proliferative phenotype and [Ca(2+)]i overload. It can be concluded from
      the results that proliferation of PMVECs plays an important role in the
      pathogenesis of BLM-induced PF.

PMID- 24083994
TI  - Site-specific determinants of cutaneous melanoma: a case-case comparison of
      patients with tumors arising on the head or trunk.
AB  - BACKGROUND: Cutaneous melanomas have been hypothesized to arise through different
      pathways according to phenotype, body site, and sun exposure. To further test
      this hypothesis, we explored associations between phenotype and melanoma at
      different sites using a case-case comparative approach. METHODS: Melanoma
      patients (n = 762) aged 18 to 79 years and diagnosed from 2007 to 2010 were
      ascertained from pathology laboratories in Brisbane, Australia. Patients reported
      phenotypic information and a dermatologist counted melanocytic nevi and solar
      keratoses. We compared data for patients with trunk melanoma (n = 541, the
      reference group), head/neck melanoma (n = 122), or lentigo maligna melanoma (LMM)
      of the head/neck (n = 69). ORs and 95% confidence intervals were calculated using
      classical or polytomous logistic regression models. RESULTS: Compared with trunk
      melanoma patients, those with head/neck melanoma were significantly less likely
      to have high nevus counts (>=135: OR = 0.27; Ptrend = 0.0004). Associations
      between category of nevus count and LMM head/neck were weaker and significantly
      different (>=135: OR = 1.09; Ptrend = 0.69; Phomogeneity = 0.02). Patients with
      head/neck melanoma were more likely than those with truncal melanoma to have high
      solar keratosis counts (>=7: OR = 1.78, Ptrend = 0.04). Again, associations with
      LMM head/neck were weaker, albeit not significantly different (>=7: OR = 1.61;
      Ptrend = 0.42; Phomogeneity = 0.86). CONCLUSION: Trunk melanomas are more
      strongly associated with nevus counts than head/neck melanomas, but are less
      strongly associated with number of solar keratoses, a marker of chronic sun
      exposure. IMPACT: These findings underscore the notion that melanomas on the
      trunk typically arise through a causal pathway associated with nevus propensity,
      whereas melanomas on the head/neck arise through a pathway associated with
      cumulative sun exposure.

PMID- 24083996
TI  - Respect the clock.

PMID- 24083995
TI  - Loss of PTEN is associated with aggressive behavior in ERG-positive prostate
      cancer.
AB  - BACKGROUND: The associations of ERG overexpression with clinical behavior and
      molecular pathways of prostate cancer are incompletely known. We assessed the
      association of ERG expression with AR, PTEN, SPINK1, Ki-67, and EZH2 expression
      levels, deletion, and mutations of chromosomal region 3p14 and TP53, and
      clinicopathologic variables. METHODS: The material consisted of 326
      prostatectomies, 166 needle biopsies from men treated primarily with endocrine
      therapy, 177 transurethral resections of castration-resistant prostate cancers
      (CRPC), and 114 CRPC metastases obtained from 32 men. Immunohistochemistry, FISH,
      and sequencing was used for the measurements. RESULTS: ERG expression was found
      in about 45% of all patient cohorts. In a multivariate analysis, ERG expression
      showed independent value of favorable prognosis (P = 0.019). ERG positivity was
      significantly associated with loss of PTEN expression in prostatectomy (P =
      0.0348), and locally recurrent CRPCs (P = 0.0042). Loss of PTEN expression was
      associated (P = 0.0085) with shorter progression-free survival in ERG-positive,
      but not in negative cases. When metastases in each subject were compared,
      consistent ERG, PTEN, and AR expression as well as TP53 mutations were found in a
      majority of subjects. CONCLUSIONS: A similar frequency of ERG positivity from
      early to late stage of the disease suggests lack of selection of ERG expression
      during disease progression. The prognostic significance of PTEN loss solely in
      ERG-positive cases indicates interaction of these pathways. The finding of
      consistent genetic alterations in different metastases suggests that the major
      genetic alterations take place in the primary tumor. IMPACT: Interaction of PTEN
      and ERG pathways warrants further studies.

PMID- 24083997
TI  - Sinking skin flap syndrome with delayed dysautonomic syndrome-An atypical
      presentation.
AB  - INTRODUCTION: Sinking skin flap syndrome or "syndrome of the trephined" is a rare
      complication after a large craniectomy, with a sunken skin above the bone defect
      with neurological symptoms such as severe headache, mental changes, focal
      deficits, or seizures. PRESENTATION OF CASE: We report a case of 21 years old man
      with trefinated syndrome showing delayed dysautonomic changes. DISCUSSION: Our
      patient had a large bone flap defect and a VP shunt that constitute risk factors
      to develop this syndrome. Also, there is reabsorption of bone tissue while it is
      placed in subcutaneous tissue. The principal symptoms of sinking skin flap
      syndrome are severe headache, mental changes, focal deficits, or seizures. Our
      patient presented with a delayed dysautonomic syndrome, with signs and symptoms
      very characteristics. Only few cases of this syndrome were related in literature
      and none were presented with dysautonomic syndrome. CONCLUSION: We reported here
      a very uncommon case of sinking skill flap syndrome that causes a severe
      dysautonomic syndrome and worsening the patient condition.

PMID- 24083998
TI  - Cytomegalovirus seropositivity and serointensity are associated with hippocampal
      volume and verbal memory in schizophrenia and bipolar disorder.
AB  - INTRODUCTION: Cytomegalovirus (CMV) is a member of the herpesviridae family that
      has a limbic and temporal gray matter tropism. It is usually latent in humans but
      has been associated with schizophrenia, bipolar disorder and cognitive deficits
      in some populations. Hippocampal decreased volume and dysfunction play a critical
      role in these cognitive deficits. We hypothesized that CMV seropositivity and
      serointensity would be associated with hippocampal volume and cognitive
      functioning in patients with schizophrenia or bipolar disorder. METHODS: 102
      healthy controls, 118 patients with bipolar disorder and 69 patients with
      schizophrenia performed the California Verbal Learning Test (CVLT) and had blood
      samples drawn to assess CMV IgG levels. A subgroup of 52 healthy controls, 31
      patients with bipolar disorder and 27 patients with schizophrenia underwent T1
      MRI for hippocampal volumetry. We analyzed the association between CMV
      serointensity and seropositivity with hippocampal volume. We also explored the
      correlation between CMV serointensity and seropositivity and CVLT scores.
      RESULTS: In both patient groups but not in controls, higher CMV serointensity was
      significantly associated with smaller right hippocampal volume. Further, in the
      group of patients with schizophrenia but not bipolar disorder, CMV serointensity
      was negatively correlated with CVLT scores. CONCLUSION: CMV IgG titers are
      associated with decreased hippocampal volume and poorer episodic verbal memory in
      patients with schizophrenia or bipolar disorder. The mechanism of this
      association warrants further exploration.

PMID- 24083999
TI  - Effects of marine protected areas on overfished fishing stocks with multiple
      stable states.
AB  - Marine protected areas (MPAs) have attracted much attention as a tool for
      sustainable fisheries management, restoring depleted fisheries stocks and
      maintaining ecosystems. However, even with total exclusion of fishing effort,
      depleted stocks sometimes show little or no recovery over a long time period.
      Here, using a mathematical model, we show that multiple stable states may hold
      the key to understanding the tendency for fisheries stocks to recover because of
      MPAs. We find that MPAs can have either a positive effect or almost no effect on
      the recovery of depleted fishing stocks, depending on the fish migration patterns
      and the fishing policies. MPAs also reinforce ecological resilience, particularly
      for migratory species. In contrast to previous reports, our results show that
      MPAs have small or sometimes negative effects on the recovery of sedentary
      species. Unsuitable MPA planning might result in low effectiveness or even
      deterioration of the existing condition. 

PMID- 24084001
TI  - Construction of graphene oxide magnetic nanocomposites-based on-chip enzymatic
      microreactor for ultrasensitive pesticide detection.
AB  - A new strategy for facile construction of graphene oxide magnetic nanocomposites
      (GO/Fe3O4 MNCs)-based on-chip enzymatic microreactor and ultrasensitive pesticide
      detection has been proposed. GO/Fe3O4 MNCs were first prepared through an in situ
      chemical deposition strategy. Then, acetylcholinesterase (AChE) was adsorbed onto
      the GO/Fe3O4 surface to form GO/Fe3O4/AChE MNCs which was locally packed into
      PDMS microchannel simply with the help of external magnetic field to form an on
      chip enzymatic microreactor. The constructed GO/Fe3O4/AChE MNCs-based enzymatic
      microreactor not only have the magnetism of Fe3O4 NPs that make them conveniently
      manipulated by an external magnetic field, but also have the larger surface and
      excellent biocompatibility of graphene which can incorporate much more AChE
      molecules and well maintain their biological activity. On the basis of the AChE
      inhibition principle, a novel on-chip enzymatic microreactor was constructed for
      analyzing dimethoate which is usually used as a model of organophosphorus
      pesticides. Under optimal conditions, a linear relationship between the
      inhibition rates of AChE and the concentration of dimethoate from 1 to 20 MUgL(
      1) with a detection limit of 0.18 MUgL(-1) (S/N=3) was obtained. The developed
      electrophoretic and magnetic-based chip exhibited excellent reproducibility and
      stability with no decrease in the activity of enzyme for more than 20 repeated
      measurements over one week period, which provided a new and promising tool for
      the analysis of enzyme inhibitors with low cost and excellent performance.

PMID- 24084000
TI  - Spinal endomorphin 2 antinociception and the mechanisms that produce it are both
      sex- and stage of estrus cycle-dependent in rats.
AB  - Endomorphin 2 (EM2) is the predominant endogenous mu-opioid receptor (MOR) ligand
      in the spinal cord. Given its endogenous presence, antinociceptive responsiveness
      to the intrathecal application of EM2 most likely reflects its ability to
      modulate nociception when released in situ. In order to explore the physiological
      pliability of sex-dependent differences in spinal MOR-mediated antinociception,
      we investigated the antinociception produced by intrathecal EM2 in male,
      proestrus female, and diestrus female rats. Antinociception was reflected by
      changes in tail flick latency to radiant heat. In females, the spinal EM2
      antinociceptive system oscillated between analgesically active and inactive
      states. During diestrus, when circulating estrogens are low, spinal EM2
      antinociceptive responsiveness was minimal. In contrast, during proestrus, when
      circulating estrogens are high, spinal EM2 antinociception was robust and
      comparable in magnitude to that manifest by males. Furthermore, in proestrus
      females, spinal EM2 antinociception required spinal dynorphin and kappa-opioid
      receptor activation, concomitant with MOR activation. This is required for
      neither spinal EM2 antinociception in males nor the antinociception elicited in
      proestrus females by spinal sufentanil or [d-Ala(2),N-methyl-Phe(4),Gly-ol(5)]
      enkephalin, which are prototypic MOR-selective nonpeptide and peptide agonists,
      respectively. These results reveal that spinal EM2 antinociception and the
      signaling mechanisms used to produce it fundamentally differ in males and
      females. PERSPECTIVE: The inability to mount spinal EM2 antinociception during
      defined stages of the estrus (and presumably menstrual) cycle and impaired
      transition from spinal EM2 analgesically nonresponsive to responsive
      physiological states could be causally associated with the well-documented
      greater severity and frequency of chronic intractable pain syndromes in women vs
      men.

PMID- 24084002
TI  - Exploring the potentialities of comprehensive two-dimensional gas chromatography
      coupled to time of flight mass spectrometry to distinguish bivalve species:
      Comparison of two clam species (Venerupis decussata and Venerupis philippinarum).
AB  - Metabolomics represents an emerging topic that can be valuable in the knowledge
      of organism responses to different stimuli. Metabolomic studies of bivalves may
      reveal the constraints they are subjected to, and may help clarifying the
      functions most affected and the tolerance mechanisms triggered. In response to
      this approach, two-dimensional gas chromatography-time of flight mass
      spectrometry (GC*GC-ToFMS) combined with headspace solid phase microextraction
      (HS-SPME) was applied, for the first time to our knowledge, to the untargeted and
      comprehensive study of the volatile composition of clam species. Firstly,
      experimental parameters that influence the SPME extraction efficiency were
      evaluated: sample preparation mode, sample volume and SPME fiber coating. Taking
      into account the results from the optimization step, the metabolomic profiles
      were performed using 1 ml of clam soft tissues homogenized with N2 and diluted in
      deionised water (1:2, w/v), using the PDMS/DVB fiber coating. From a total of
      more than 200 compounds detected per sample, 63 were tentatively identified and
      distributed over the chemical families of hydrocarbons, ketones, aldehydes,
      alcohols, and terpenoids, which seems to arise from clams own metabolism, and/or
      from their activity as filter-feeders. The potential of this methodology to
      discriminate close related species was explored by comparing the volatile
      profiles of Venerupis philippinarum and Venerupis decussata from Ria de Aveiro,
      two clams belonging to the same genus. Both species experience different
      environment conditions, and physiological and biochemical characteristics, which
      may explain the observed differentiation between their metabolic profiles. To our
      knowledge, this is the most detailed information available so far about clam
      volatile composition, which represents a valuable data for future advanced
      studies in the ecology, toxicology and physiology of bivalves based on clams
      fingerprinting.

PMID- 24084003
TI  - Effects of patterns of walking training on metabolic health of untrained
      postmenopausal women.
AB  - PURPOSE: High-intensity aerobic interval training (AIT) has been reported to be
      more effective than continuous aerobic training (CoAT) to improve metabolic
      health. The aim of our study was to investigate whether moderate-intensity AIT is
      more effective than CoAT on metabolic health when applied to a walking training
      program. DESIGN/METHODS: Thirty-two postmenopausal women (55.37 +/- 3.46 years)
      were investigated for body composition, plasma glucose, insulin, lipids,
      adiponectin, HOMA-IR, HOMA-AD, aerobic fitness, dietary habits, and spontaneous
      physical activity, and randomly assigned to one of two different walking training
      programs: CoAT or AIT. RESULTS: CoAT and AIT elicited the same physiological
      benefits, including: reduction of plasma glucose, insulin, HOMA-IR and HOMA-AD,
      and increase of plasma HDL-C, adiponectin, and aerobic fitness. CONCLUSIONS: An
      AIT scheme as part of an outdoor walking training program elicits the same
      physiological adaptations as a CoAT scheme, probably because walking does not
      promote exercise intensities that elicit greater effects.

PMID- 24084004
TI  - Recombinant expression of Laceyella sacchari thermitase in Lactococcus lactis.
AB  - Thermitase (EC 3.4.21.66) is a thermostable endo-protease with the ability to
      convert various food relevant substrates into low-molecular weight peptides. A
      thermitase produced by Laceyella sacchari strain DSM43353 was found to have a
      mature amino acid sequence nearly identical to that of the original thermitase
      isolated from Thermoactinomyces vulgaris. The DSM43353 thermitase gene sequence
      contains a pro-peptide including parts of an I9 inhibitor motif. Expression of
      the thermitase gene in the Lactococcus lactis P170 expression system allowed
      secretion of stable thermitase in an auto-induced fermentation setup at 30
      degrees C. Thermitase accumulated in the culture supernatant during batch
      fermentations and was easily activated at 50 degrees C or by prolonged dialysis.
      The activation step resulted in an almost complete degradation of endogenous L.
      lactis host proteins present in the supernatant. Mature activated product was
      stable at 50 degrees C and functional at pH values between pH 6 and pH 11,
      suggesting that substrate hydrolysis can be performed over a broad range of pH
      values. The L. lactis based P170 expression system is a simple and safe system
      for obtaining food compatible thermitase in the range of 100 mg/L.

PMID- 24084005
TI  - Cloning, expression, purification and characterization of an iron-dependent
      regulator protein from Thermobifida fusca.
AB  - Iron-dependent regulators (IdeRs) control the transcription of a variety of genes
      associated with iron homeostasis in Gram-positive bacteria. In this study we
      report the cloning of a putative IdeR gene from the moderate thermophile
      Thermobifida fusca into the pET-21a(+) expression vector. The expressed protein,
      Tf-IdeR, was purified using immobilized metal affinity and size-exclusion
      chromatography, and yielded approximately 12-16 mg of protein per liter of
      culture. The purified Tf-IdeR protein binds the tox operator sequence in the
      presence of divalent metal ions. Two Tf-IdeR binding sites were identified in the
      T. fusca genome upstream of a putative enterobactin exporter and a putative ABC
      type multidrug transporter.

PMID- 24084006
TI  - Functional expression of hepassocin in Escherichia coli using SUMO fusion partner
      and molecular chaperones.
AB  - Human hepassocin (HPS) is a hepatic growth factor which can accelerate hepatocyte
      proliferation in vivo and protect against liver injury. Previous reports have
      shown that HPS expressed in Escherichia coli resulted in inclusion bodies or low
      yield. In this study, the application of small ubiquitin-related modifier (SUMO)
      fusion technology in combined with four different chaperone teams on the soluble
      expression of recombinant HPS protein were explored and analyzed. The soluble
      expression of HPS was improved significantly by SUMO fusion and co-expression
      with trigger factor (Tf) chaperone, which was identified by SDS-PAGE and Western
      blotting. The fusion protein was purified to 90% purity by metal chelate
      chromatography with a yield of 98 mg per liter fermentation culture. Finally,
      about 19 mg HPS was obtained from 1l of fermentation culture with no less than
      96% purity following purification of the SUMO protease cleavage and re-purified
      by the Ni-NTA resin chromatography, which was the highest yield of HPS reported
      so far with less time and effort. The recombinant HPS significantly stimulated
      the proliferation of human hepatic cell line L02 cells. The present work provides
      an effective system for soluble expression of functional HPS, which will
      facilitate the clinical developments of recombinant protein drugs.

PMID- 24084007
TI  - Lyso-myristoyl phosphatidylcholine micelles sustain the activity of Dengue non
      structural (NS) protein 3 protease domain fused with the full-length NS2B.
AB  - Dengue virus (DENV), a member of the flavivirus genus, affects 50-100 million
      people in tropical and sub-tropical regions. The DENV protease domain is located
      at the N-terminus of the NS3 protease and requires for its enzymatic activity a
      hydrophilic segment of the NS2B that acts as a cofactor. The protease is an
      important antiviral drug target because it plays a crucial role in virus
      replication by cleaving the genome-coded polypeptide into mature functional
      proteins. Currently, there are no drugs to inhibit DENV protease activity. Most
      structural and functional studies have been conducted using protein constructs
      containing the NS3 protease domain connected to a soluble segment of the NS2B
      membrane protein via a nine-residue linker. For in vitro structural and
      functional studies, it would be useful to produce a natural form of the DENV
      protease containing the NS3 protease domain and the full-length NS2B protein.
      Herein, we describe the expression and purification of a natural form of DENV
      protease (NS2BFL-NS3pro) containing the full-length NS2B protein and the protease
      domain of NS3 (NS3pro). The protease was expressed and purified in detergent
      micelles necessary for its folding. Our results show that this purified protein
      was active in detergent micelles such as lyso-myristoyl phosphatidylcholine
      (LMPC). These findings should facilitate further structural and functional
      studies of the protease and will facilitate drug discovery targeting DENV.

PMID- 24084008
TI  - Molecular characterization of a glycosyl hydrolase family 10 xylanase from
      Aspergillus niger.
AB  - A gene coding for an endo-beta-1,4-xylanase (XlnA) (glycosyl hydrolase family 10)
      from Aspergillus niger DSM 1957 was cloned and sequenced. The cDNA sequence (984
      bp) and its putative endoxylanase (327 aa protein with a predicted molecular mass
      of 35.5 kDa and pI 6.23) showed 91.3-99.5% and 96.3-99.1% identities with cDNA
      sequences and their corresponding endoxylanases from A. niger strains from
      GenBank, respectively. The cDNA was expressed in Pichia pastoris GS115 under the
      control of AOX1 promoter at a level of 46.4 U/ml culture supernatant, after 144 h
      of growth at 30 degrees C in YP medium induced with 0.5% (v/v) of methanol. The
      molecular mass of the purified XlnA determined by SDS-PAGE was 35.5k Da with a
      specific activity of 808.5 U/mg towards 1% (w/v) of birch wood xylan. Temperature
      and pH optimum were observed at 50 degrees C and pH 7.0, respectively. The enzyme
      was stable over a temperature range of 25-40 degrees C and at pH range of 4.5-8.5
      and resistant to Tween 80 and acetone. The K(m) and V(max) value obtained for the
      purified xylanase were 25.5mg/ml and 5000 MUmol/min/mg protein with birch wood
      xylan as substrate, respectively. The xylanase was free of cellulase and
      mannanase activity but highly active towards birch wood xylan. The major products
      of the birch wood xylan hydrolysis were predicted as xylotriose, xylotetraose,
      and xylopentose. The biochemical characteristics suggested that the recombinant
      xylanase has a potential application, including use as a feed enzyme.

PMID- 24084009
TI  - The Fh8 tag: a fusion partner for simple and cost-effective protein purification
      in Escherichia coli.
AB  - Downstream processing is still a major bottleneck in recombinant protein
      production representing most of its costs. Hence, there is a continuing demand of
      novel and cost-effective purification processes aiming at the recovery of pure
      and active target protein. In this work, a novel purification methodology is
      presented, using the Fh8 solubility enhancer tag as fusion handle. The binding
      properties of Fh8 tag to a hydrophobic matrix were first studied via hydrophobic
      interaction chromatography (HIC). The Fh8 tag was then evaluated as a
      purification handle by its fusion to green fluorescent protein and superoxide
      dismutase. The purification efficiency of the Fh8-HIC strategy was compared to
      the immobilized metal ion affinity chromatography (IMAC) using the His6 tag.
      Results showed that the Fh8-HIC binding mechanism is calcium-dependent in a low
      salt medium, making the purification process highly selective. Both target
      proteins were biologically active, even when fused to Fh8, and were successfully
      purified by HIC, achieving efficiencies identical to those of IMAC. Thus, the Fh8
      acts as an effective affinity tag that, together with its previously reported
      solubility enhancer capability, allows for the design of inexpensive and
      successful recombinant protein production processes in Escherichia coli. 

PMID- 24084010
TI  - Organ donation as transition work: Policy discourse and clinical practice in The
      Netherlands.
AB  - An increasing number of patients become eligible for organ transplants. In the
      Netherlands, at the level of policy discourse, growing waiting lists are often
      referred to as a persistent "shortage" of organs, producing a "public health
      crisis." In this way, organ donation is presented as an ethical, social, and
      medical necessity. Likewise, policy discourse offers a range of seemingly
      unambiguous solutions: improving logistical infrastructure at the level of
      hospitals, developing organizational and legal protocols, as well as public
      information campaigns. Instead of taking these problem and solution definitions
      as given, we critically examine the relationship between policy discourse and
      clinical practice. Based on a historical review, first, we trace the key moments
      of transformation where organ donation became naturalized in Dutch policy
      discourse, particularly in its altruistic connotation. Second, based on in-depth
      interviews with medical professionals, we show how those involved in organ
      donation continue to struggle with the controversial nature of their clinical
      practice. More specifically, we highlight their use of different forms of
      knowledge that underlie clinicians' "transition work": from losing a patient to
      "gaining" a donor. 

PMID- 24084011
TI  - Pregnenolone sulfate: from steroid metabolite to TRP channel ligand.
AB  - Pregnenolone sulfate is a steroid metabolite with a plethora of actions and
      functions. As a neurosteroid, pregnenolone sulfate modulates a variety of ion
      channels, transporters, and enzymes. Interestingly, as a sulfated steroid,
      pregnenolone sulfate is not the final- or waste-product of pregnenolone being
      sulfated via a phase II metabolism reaction and renally excreted, as one would
      presume from the pharmacology textbook knowledge. Pregnenolone sulfate is also
      the source and thereby the starting point for subsequent steroid synthesis
      pathways. Most recently, pregnenolone sulfate has been functionally "upgraded"
      from modulator of ion channels to an activating ion channel ligand. This review
      will focus on molecular aspects of the neurosteroid, pregnenolone sulfate, its
      metabolism, concentrations in serum and tissues and last not least will summarize
      the functional data. 

PMID- 24084012
TI  - Yields, phenolic profiles and antioxidant activities of Ziziphus jujube Mill. in
      response to different fertilization treatments.
AB  - Increasing demand for more jujube (Ziziphus jujube Mill.) production requires
      understanding the specific fertilization needs of jujube trees. This study was
      conducted to compare fruit yields, phenolic profiles and antioxidant activity of
      jujube in response to different fertilizers. Application of organic fertilizer
      appeared to enhance the phenolics and antioxidant activity accumulation of
      jujubes, compared to conventional fertilized jujubes. Amongst inorganic
      fertilizers, supplemental potassium as an individual nutrient improved the
      accumulation of phenolics in jujubes. Our results demonstrate that phenolics
      levels and antioxidant activity of jujube can be manipulated through fertilizer
      management and tracked by following proanthocyanidin concentrations. In a
      practical production context, the combination of organic fertilizers and
      inorganic fertilizers such as more supplemental individual potassium, and less
      supplemental individual nitrogen and phosphorus, might be the best management
      combination for achieving higher phenolic concentration, stronger antioxidant
      activity and a good harvest. 

PMID- 24084013
TI  - Conductance studies on complex formation between c-methylcalix[4]resorcinarene
      and titanium (III) in acetonitrile-H2O binary solutions.
AB  - Calixresorcinarenes have proved to be unique molecules for molecular recognition
      via hydrogen bonding, hydrophobic and ionic interactions with suitable substrates
      such as cations. The study of the interactions involved in the complexation of
      different cations with calixresorcinarenes in solvent mixtures is important for a
      better understanding of the mechanism of biological transport, molecular
      recognition, and other analytical applications. This article summarizes different
      aspects of the complexes of the Ti(3+) metal cation with c
      methylcalix[4]resorcinarene (CMCR) as studied by conductometry in acetonitrile
      (AN)-water (H2O) binary mixtures at different temperatures. Conductance data show
      that the metal cation/ligand (ML) stoichiometry of the complexes in solution is
      1:1 in all cases. Non-linear behaviour was observed for the variation of logKf of
      the complexes vs. the composition of the binary solvent mixtures. Selectivity of
      CMCR for the Ti(3+) cation is sensitive to solvent composition; in some cases and
      at certain compositions of the mixed solvent systems, the selectivity order is
      changed. Values of thermodynamic parameters (DeltaH(c)(0), DeltaS(c)(0)) for
      formation of the CMCR-Ti(3+) complexes in AN-H2O binary systems were obtained
      from the temperature dependence of stability constants, and the results show that
      the thermodynamics of complexation reactions are affected by the nature and
      composition of the mixed solvents.

PMID- 24084014
TI  - Identification of new natural DNA G-quadruplex binders selected by a structure
      based virtual screening approach.
AB  - The G-quadruplex DNA structures are mainly present at the terminal portion of
      telomeres and can be stabilized by ligands able to recognize them in a specific
      manner. The recognition process is usually related to the inhibition of the
      enzyme telomerase indirectly involved and over-expressed in a high percentage of
      human tumors. There are several ligands, characterized by different chemical
      structures, already reported in the literature for their ability to bind and
      stabilize the G-quadruplex structures. Using the structural and biological
      information available on these structures; we performed a high throughput in
      silico screening of commercially natural compounds databases by means of a
      structure-based approach followed by docking experiments against the human
      telomeric sequence d[AG3(T2AG3)3]. We identified 12 best hits characterized by
      different chemical scaffolds and conformational and physicochemical properties.
      All of them were associated to an improved theoretical binding affinity with
      respect to that of known selective G-binders. Among these hits there is a
      chalcone derivative; structurally very similar to the polyphenol butein; known to
      remarkably inhibit the telomerase activity.

PMID- 24084015
TI  - Gaultheria: Phytochemical and pharmacological characteristics.
AB  - The genus Gaultheria, comprised of approximately 134 species, is mostly used in
      ethnic drugs to cure rheumatism and relieve pain. Phytochemical investigations of
      the genus Gaultheria have revealed the presence of methyl salicylate derivatives,
      C6-C3 constituents, organic acids, terpenoids, steroids, and other compounds.
      Methyl salicylate glycoside is considered as a characteristic ingredient in this
      genus, whose anti-rheumatic effects may have a new mechanism of action. In this
      review, comprehensive information on the phytochemistry, volatile components and
      the pharmacology of the genus Gaultheria is provided to explore its potential and
      advance research.

PMID- 24084016
TI  - Anti-inflammatory activity of iridoids and verbascoside isolated from Castilleja
      tenuiflora.
AB  - Castilleja tenuiflora (Orobanchaceae) has been used in Mexican traditional
      medicine as a treatment for cough, dysentery, anxiety, nausea and vomiting as
      well as hepatic and gastrointestinal diseases. The ethanolic extract of the
      aerial parts of Castilleja tenuiflora was separated by silica gel column
      chromatography. The fractions were evaluated using the induced edema acetate 12-O
      tetradecanoylphorbol (TPA) anti-inflammatory activity model. The most active
      fraction was subjected to medium-pressure liquid chromatography (MPLC) with UV
      detection at 206 and 240 nm. The following iridoids were isolated: geniposidic
      acid, aucubin, bartioside, 8-epi-loganin, mussaenoside, and the phenylpropanoid
      verbascoside. The most active iridoid was geniposidic acid, which was more active
      than the control (indomethacin), and the least active iridoid was mussaenoside. 8
      epi-Loganin, and mussaenoside have not been previously reported to be anti
      inflammatory compounds. The results of these investigations confirm the potential
      of Mexican plants for the production of bioactive compounds and validate the
      ethnomedical use of Castilleja tenuiflora-like anti-inflammatory plants. 

PMID- 24084017
TI  - Syntheses of precursors and reference compounds of the melanin-concentrating
      hormone receptor 1 (MCHR1) tracers [11C]SNAP-7941 and [18F]FE@SNAP for positron
      emission tomography.
AB  - The MCH receptor has been revealed as a target of great interest in positron
      emission tomography imaging. The receptor's eponymous substrate melanin
      concentrating hormone (MCH) is a cyclic peptide hormone, which is located
      predominantly in the hypothalamus with a major influence on energy and weight
      regulation as well as water balance and memory. Therefore, it is thought to play
      an important role in the pathophysiology of adiposity, which is nowadays a big
      issue worldwide. Based on the selective and high-affinity MCH receptor 1
      antagonist SNAP-7941, a series of novel SNAP derivatives has been developed to
      provide different precursors and reference compounds for the radiosyntheses of
      the novel PET radiotracers [(11)C]SNAP-7941 and [(18)F]FE@SNAP. Positron emission
      tomography promotes a better understanding of physiologic parameters on a
      molecular level, thus giving a deeper insight into MCHR1 related processes as
      adiposity.

PMID- 24084018
TI  - Metabolite analysis of toosendanin by an ultra-high performance liquid
      chromatography-quadrupole-time of flight mass spectrometry technique.
AB  - Toosendanin is the major bioactive component of Melia toosendan Sieb. et Zucc.,
      which is traditionally used for treatment of abdominal pain and as an
      insecticide. Previous studies reported that toosendanin possesses hepatotoxicity,
      but the mechanism remains unknown. Its bioavailability in rats is low, which
      indicates the hepatotoxicity might be induced by its metabolites. In this
      connection, in the current study, we examined the metabolites obtained by
      incubating toosendanin with human live microsomes, and then six of these
      metabolites (M1-M6) were identified for the first time by ultra-high performance
      liquid chromatography-quadrupole-time of flight mass spectrometry (UHPLC-Q
      TOF/MS). Further analysis on the MS spectra showed M1, M2, and M3 are oxidative
      products and M6 is a dehydrogenation product, while M4 and M5 are oxidative and
      dehydrogenation products of toosendanin. Moreover, their possible structures were
      deduced from the MS/MS spectral features. Quantitative analysis demonstrated that
      M1-M5 levels rapidly increased and reached a plateau at 30 min, while M6 rapidly
      reached a maximal level at 20 min and then decreased slowly afterwards. These
      findings have provided valuable data not only for understanding the metabolic
      fate of toosendanin in liver microsomes, but also for elucidating the possible
      molecular mechanism of its hepatotoxicity. 

PMID- 24084019
TI  - Effect of black grape juice against heart damage from acute gamma TBI in rats.
AB  - The aim of this study was to evaluate the potential positive effect of black
      grape juice (BGJ) on lipid peroxidation considering Total Body Irradiation (TBI)
      in Wistar rats. As a potential feasible means of evaluation in situ, blood serum
      lactate dehydrogenase (LDH) levels were evaluated as a marker for heart damage
      from acute radiation syndrome (ARS). Twenty rats were divided into four groups,
      two of them being irradiated by gamma-rays from a Co-60 source. Animals were
      treated by gavage with 2 mL per day of BGJ or placebo for one week before and 4
      days after 6 Gy whole body gamma-irradiation, when they were euthanasiated. LDH
      on serum and lipid peroxidation on heart tissue were evaluated. High
      concentration of metabolites from lipid peroxidation in heart, and high LDH level
      on serum were found only in gamma-irradiated group given placebo, mainly at the
      first 24 h after radiation. Phytochemical analysis of BGJ was performed by
      determining total phenolics, flavonoids, and tannins followed by a high
      performance liquid chromatography (HPLC/DAD) analysis, which showed resveratrol
      as the major constituent. Results suggest that BGJ is a good protective candidate
      compound against heart damage from ARS and its effects suggest its use as a
      radiomodifier. 

PMID- 24084020
TI  - Intracellular environment-responsive stabilization of polymer vesicles formed
      from head-tail type polycations composed of a polyamidoamine dendron and poly(L
      lysine).
AB  - For the development of effective drug carriers, nanocapsules that respond to
      micro-environmental changes including a decrease in pH and a reductive
      environment were prepared by the stabilization of polymer vesicles formed from
      head-tail type polycations, composed of a polyamidoamine dendron head and a
      poly(L-lysine) tail (PAMAM dendron-PLL), through the introduction of disulfide
      bonds between the PLL tails. Disulfide bonds were successfully introduced through
      the reaction of Lys residues in the PAMAM dendron-PLL polymer vesicles with 2
      iminothiolane. The stabilization of PAMAM dendron-PLL polymer vesicles was
      confirmed by dynamic light scattering measurements. In acid-base titration
      experiments, nanocapsules cross-linked by disulfide bonds had a buffering effect
      during the cellular uptake process. The PAMAM dendron-PLL nanocapsules were used
      to incorporate the fluorescent dyes rhodamine 6G and fluorescein as a drug model.
      Cationic rhodamine 6G was generally not released from the nanocapsules because of
      the electrostatic barrier of the PLL membrane. However, the nanocapsules were
      destabilized at high glutathione concentrations corresponding to intracellular
      concentrations. Rhodamine 6G was immediately released from the nanocapsules
      because of destabilization upon the cleavage of disulfide bonds. This release of
      rhodamine 6G from the nanocapsules was also observed in HeLa cells by laser
      confocal microscopy. 

PMID- 24084021
TI  - Lepidotrichilins A and B, new protolimonoids with cytotoxic activity from
      Trichilia lepidota (Meliaceae).
AB  - Two novel protolimonoids, named lepidotrichilins A (1) and B (2), four known
      protolimonoids, 21,23-epoxy-7alpha-21alpha-dihydroxyapotirucalla-14,24-dien-3-one
      (3), 21,23-epoxy-7alpha-21beta-dihydroxyapotiru-calla-14,24-dien-3-one (4),
      dysorone D (5), deoxy-flindissone (6), and the two steroids beta-sitosterol (7)
      and stigmasterol (8) were identified in leaves of Trichilia lepidota subsp.
      schumanniana (Harms) T.D. Pennington. From wood the coumarin scopoletin (9) was
      isolated. The structures were established by NMR (1D (1)H and (13)C-NMR and 2D
      (1)H-(1)H COSY, HMQC and HMBC), mass spectroscopy and infrared (IR) spectral
      data. The hexane and methanol extracts of the leaves, the protolimonoids
      lepidotrichilins A (1) and B (2) (IC50 42.7 ug mL(-1)) and the protolimonoid
      deoxy-flindissone (6; IC50 9.3 ugmL(-1)) exhibited significant cytotoxic activity
      against the MOLT-4 and U937 leukemic cell lines.

PMID- 24084022
TI  - Qualitative and quantitative analysis of Andrographis paniculata by rapid
      resolution liquid chromatography/time-of-flight mass spectrometry.
AB  - A rapid resolution liquid chromatography/time-of-flight tandem mass spectrometry
      (RRLC-TOF/MS) method was developed for qualitative and quantitative analysis of
      the major chemical constituents in Andrographis paniculata. Fifteen compounds,
      including flavonoids and diterpenoid lactones, were unambiguously or tentatively
      identified in 10 min by comparing their retention times and accurate masses with
      standards or literature data. The characteristic fragmentation patterns of
      flavonoids and diterpenoid lactones were summarized, and the structures of the
      unknown compounds were predicted. Andrographolide, dehydroandrographolide and
      neoandrographolide were further quantified as marker substances. It was found
      that the calibration curves for all analytes showed good linearity (R2 > 0.9995)
      within the test ranges. The overall limits of detection (LODs) and limits of
      quantification (LOQs) were 0.02 MUg/mL to 0.06 MUg/mL and 0.06 MUg/mL to 0.2
      MUg/mL, respectively. The relative standard deviations (RSDs) for intra- and
      inter-day precisions were below 3.3% and 4.2%, respectively. The mean recovery
      rates ranged from 96.7% to 104.5% with the relative standard deviations (RSDs)
      less than 2.72%. It is concluded that RRLC-TOF/MS is powerful and practical in
      qualitative and quantitative analysis of complex plant samples due to time
      savings, sensitivity, precision, accuracy and lowering solvent consumption.

PMID- 24084023
TI  - In vitro anti-Candida activity of certain new 3-(1H-imidazol-1-yl)propan-1-one
      oxime esters.
AB  - Anti-Candida activities of certain new oximes 4a-d and their respective aromatic
      esters 5a-l are reported. The tested compounds 4a-d and 5a-l exhibited better
      anti-Candida profiles than fluconazole. Compound 5j, namely (E)-3-(1H-imidazol-1
      yl)-1-phenylpropan-1-one O-4-chlorobenzoyl oxime emerged as the most active
      congener, with a MIC value of 0.0054 umol/mL being more potent than both
      fluconazole (MIC > 1.6325 umol/mL) and miconazole (MIC value = 0.0188 umol/mL) as
      a new anti-Candida albicans agent. 

PMID- 24084024
TI  - Promising low-toxicity of viologen-phosphorus dendrimers against embryonic mouse
      hippocampal cells.
AB  - A new class of viologen-phosphorus dendrimers (VPDs) has been recently shown to
      possess the ability to inhibit neurodegenerative processes in vitro.
      Nevertheless, in the Central Nervous Systems domain, there is little information
      on their impact on cell functions, especially on neuronal cells. In this work, we
      examined the influence of two VPD (VPD1 and VPD3) of zero generation (G0) on
      murine hippocampal cell line (named mHippoE-18). Extended analyses of cell
      responses to these nanomolecules comprised cytotoxicity test, reactive oxygen
      species (ROS) generation studies, mitochondrial membrane potential (DeltaPsim)
      assay, cell death detection, cell morphology assessment, cell cycle studies, as
      well as measurements of catalase (CAT) activity and glutathione (GSH) level. The
      results indicate that VPD1 is more toxic than VPD3. However, these two tested
      dendrimers did not cause a strong cellular response, and induced a low level of
      apoptosis. Interestingly, VPD1 and VPD3 treatment led to a small decline in ROS
      level compared to untreated cells, which correlated with slightly increased
      catalase activity. This result indicates that the VPDs can indirectly lower the
      level of ROS in cells. Summarising, low-cytotoxicity on mHippoE-18 cells together
      with their ability to quench ROS, make the VPDs very promising nanodevices for
      future applications in the biomedical field as nanocarriers and/or drugs per se. 

PMID- 24084025
TI  - Glycosyl-Nucleolipids as new bioinspired amphiphiles.
AB  - Four new Glycosyl-NucleoLipid (GNL) analogs featuring either a single
      fluorocarbon or double hydrocarbon chains were synthesized in good yields from
      azido thymidine as starting material. Physicochemical studies (surface tension
      measurements, differential scanning calorimetry) indicate that hydroxybutanamide
      based GNLs feature endothermic phase transition temperatures like the previously
      reported double chain glycerol-based GNLs. The second generation of GNFs
      featuring a free nucleobase reported here presents a better surface activity
      (lower glim) compared to the first generation of GNFs. 

PMID- 24084026
TI  - Mechanistic implications of persulfenate and persulfide binding in the active
      site of cysteine dioxygenase.
AB  - Describing the organization of substrates and substrate analogues in the active
      site of cysteine dioxygenase identifies potential intermediates in this critical
      yet poorly understood reaction, the oxidation of cysteine to cysteine sulfinic
      acid. The fortuitous formation of persulfides under crystallization conditions
      has allowed their binding in the active site of cysteine dioxygenase to be
      studied. The crystal structures of cysteine persulfide and 3-mercaptopropionic
      acid persulfide bound to iron(II) in the active site show that binding of the
      persulfide occurs via the distal sulfide and, in the case of the cysteine
      persulfide, the amine also binds. Persulfide was detected by mass spectrometry in
      both the crystal and the drop, suggesting its origin is chemical rather than
      enzymatic. A mechanism involving the formation of the relevant disulfide from
      sulfide produced by hydrolysis of dithionite is proposed. In comparison,
      persulfenate {observed bound to cysteine dioxygenase [Simmons, C. R., et al.
      (2008) Biochemistry 47, 11390]} is shown through mass spectrometry to occur only
      in the crystal and not in the surrounding drop, suggesting that in the
      crystalline state the persulfenate does not lie on the reaction pathway.
      Stabilization of both the persulfenate and the persulfides does, however, suggest
      the position in which dioxygen binds during catalysis. 

PMID- 24084027
TI  - Mortality landscape in the global burden of diseases, injuries and risk factors
      study.
AB  - The Global Burden of Diseases, Injuries and Risk Factors Study 2010 (GBD 2010) is
      an initiative that involved 486 scientists from 302 institutions in 50 countries,
      under the leadership of a consortium formed by the Institute for Health Metrics
      and Evaluation of the University of Washington, World Health Organization, the
      University of Queensland School of Population Health, the Harvard School of
      Public Health, the Johns Hopkins Bloomberg School of Public Health, the
      University of Tokyo and Imperial College London. The study has provided a state
      of the art understanding of the burden of 67 risk factors and their clusters, 291
      diseases and injuries on global, regional and national levels in period from 1990
      to 2010 for 187 countries. GBD 2010 estimates covered both mortality (expressed
      in number of deaths, years of life lost (YLL) due to premature mortality) and
      morbidity (mainly expressed as years lived with disability (YLD)), while the
      incidence and prevalence were not reported for majority of causes so far,
      although they were accounted and used for YLD calculations. Finally, each disease
      and risk factor was presented in terms of the disability-adjusted years of life
      (DALY) that is merely a sum of YLL and YLD. The major published results of GBD
      2010 cover global and regional levels for all diseases and risk factors. Reports
      focused on specific conditions are also available. At country-level detailed
      estimates are published for UK, China and USA, and data on other countries are
      accessible only as aggregate partial representation via web-based tools. 

PMID- 24084028
TI  - Asbestos-induced mesothelioma: is fiber biopersistence really a critical factor?
AB  - This Commentary highlights the research by Qi et al detailing the similarities
      and differences between crocidolite and chrysotile asbestos in terms of their
      transcriptional effects and transforming actions in human mesothelial cells.

PMID- 24084029
TI  - An 11-year-old girl with recurrent bacterial meningitis due to liquorrhea caused
      by bone malformation of the skull base.
AB  - The patient is a healthy 11-year-old girl with no history of trauma or hearing
      impairment. She developed pneumococcal meningitis three times, at ages 7, 10, and
      11. Intracranial examination revealed, pore expansion and cerebrospinal fluid
      leakage in the right internal acoustic foramen, which were attributed to a bone
      malformation of the base of the skull. A procedure was performed to close the
      cerebrospinal fluid leakage; no relapse has been observed thus far. Previous case
      reports indicate that repetitive bacterial meningitis is often caused by internal
      ear malformation, trauma, tumors, or surgical operation. This case suggests the
      possibility that underlying disorders may not be apparent in cases of repetitive
      bacterial meningitis and, more proactive investigations are required to prevent
      further recurrence of meningitis. 

PMID- 24084030
TI  - Exponential passivity of memristive neural networks with time delays.
AB  - Memristive neural networks are studied across many fields of science. To uncover
      their structural design principles, the paper introduces a general class of
      memristive neural networks with time delays. Passivity analysis is conducted by
      constructing suitable Lyapunov functional. The analysis in the paper employs the
      results from the theories of nonsmooth analysis and linear matrix inequalities. A
      numerical example is provided to illustrate the effectiveness and less
      conservatism of the proposed results. 

PMID- 24084031
TI  - Insulin and leptin levels in obese patients with and without breast cancer.
AB  - BACKGROUND: Leptin has been associated with progression and poor survival in BC.
      Moreover, it is still controversial as to whether the effect of leptin depends
      only on its correlation with body mass index (BMI), or could be a direct role of
      adipokine in the development of BC. The aim of this study was to identify if
      there was a difference between serum leptin levels and insulin in obese patients
      with and without BC. PATIENTS AND METHODS: A cross-sectional study was made in
      156 women, a group of 78 with obesity and BC and 78 with obesity without BC. When
      subjects agreed to participate, written informed consent was obtained from all
      subjects. Biochemical variables such as glucose, triglycerides, high-density and
      low-density lipoprotein, cholesterol, insulin, and leptin were measured and
      homeostasis model assessment (HOMA-IR) was calculated. RESULTS: The age, number
      of parities, glucose, HOMA-IR, and leptin were significantly different at P <
      .05. CONCLUSION: Serum leptin levels and leptin/BMI ratio were statistically
      significantly increased in patients with BC.

PMID- 24084032
TI  - A comparison of epidemiology, biology, and prognosis of inflammatory breast
      cancer in Japanese and US populations.
AB  - BACKGROUND: The epidemiology of inflammatory breast cancer (IBC) in East Asia has
      not been fully investigated. We hypothesized the epidemiologic factors associated
      with IBC in Japanese populations are different from other populations. To
      determine this, we conducted a comparison study assessing multiple clinically
      relevant risk factors. PATIENTS AND METHODS: Patients diagnosed with IBC at St.
      Luke's International Hospital (SLIH) in Tokyo, Japan, and at the University of
      Texas MD Anderson Cancer Center (MDA) in Houston, Texas, from 2003 to 2009 were
      identified via the electronic medical records. Stage IV patients were excluded.
      Epidemiological, biological, and overall survival (OS) data were collected and
      compared. After all patient populations were combined, Cox proportional hazard
      regression analysis was performed. RESULTS: Twenty-two patients at SLIH and 384
      patients at MDA were identified. No differences were found for IBC between SLIH
      and MDA regarding age at diagnosis (P = .898), hormone receptor status (P =
      .144), overexpression of HER2 (P = .136), or OS (P = .323), however, BMI (P <
      .01) and nuclear grade (NG) (P < .01) in Japanese patients were lower than those
      of US patients. Cox proportional hazard regression analysis revealed ER status
      and race were associated with OS. CONCLUSION: Despite the small number of
      patients enrolled, IBC in a Japanese population demonstrated lower BMI and lower
      NG than IBC in a US population with no difference in survival. ER status and race
      were prognostic factors when the 2 populations were combined. To more robustly
      define IBC among East Asian individuals, we have started to register Japanese
      patients with an International IBC Registry.

PMID- 24084034
TI  - Ixeris dentata-induced regulation of amylase synthesis and secretion in glucose
      treated human salivary gland cells.
AB  - The endoplasmic reticulum (ER) is an organelle which controls synthesis of
      secretory and membrane proteins. Alterations in protein folding capacity, leading
      to ER stress, can be observed in patients with diabetes and related diseases such
      as xerostomia. The objectives of this study were to investigate the effects of
      Ixeris dentata (IXD) extract, which has been used for diabetes treatment, and
      compounds purified from IXD, 8-epidesacylcynaropicrin-3-O-beta-glucopyranoside
      (ID-57D), on amylase synthesis and secretion in human salivary gland (HSG) cells
      exposed to a high concentration of glucose. A high concentration of glucose in
      the experimental medium of cultured cells can model diabetes in vitro. IXD
      extracts and ID-57D increased oxidative folding-associated protein expression,
      including p-IRE-1alpha, PDI and ERO-1alpha, with the enhanced oxidative folding
      pattern seen in HSG cells transiently exposed to a high concentration of glucose.
      Moreover, the treatments reduced the ER stress response, such as the expression
      of GRP78, maintaining amylase synthesis and secretion in chronically glucose
      exposed HSG cells. This study suggests the potential therapeutic value of IXD
      extract for the treatment of diabetes or its complications such as xerostomia. 

PMID- 24084033
TI  - An update on oxidative stress-mediated organ pathophysiology.
AB  - Exposure to environmental pollutants and drugs can result in pathophysiological
      situations in the body. Research in this area is essential as the knowledge on
      cellular survival and death would help in designing effective therapeutic
      strategies that are needed for the maintenance of the normal physiological
      functions of the body. In this regard, naturally occurring bio-molecules can be
      considered as potential therapeutic targets as they are normally available in
      commonly consumed foodstuffs and are thought to have minimum side effects. This
      review article describes the detailed mechanisms of oxidative stress-mediated
      organ pathophysiology and the ultimate fate of the cells either to survive or to
      undergo necrotic or apoptotic death. The mechanisms underlying the beneficial
      role of a number of naturally occurring bioactive molecules in oxidative stress
      mediated organ pathophysiology have also been included in the review. The review
      provides useful information about the recent progress in understanding the
      mechanism(s) of various types of organ pathophysiology, the complex cross-talk
      between these pathways, as well as their modulation in stressed conditions.
      Additionally, it suggests possible therapeutic applications of a number of
      naturally occurring bioactive molecules in conditions involving oxidative stress.

PMID- 24084035
TI  - Subchronic toxicity study of ulvan from Ulva pertusa (Chlorophyta) in Wistar
      rats.
AB  - Ulvan extracted from Ulva pertusa (Chlorophyta) is a group of sulfated
      heteropolysaccharide, for simplicity, the sulfated polysaccharide is referred to
      as ulvan in this paper. To our knowledge, there is no detailed report
      investigating the toxicity of ulvan. In this study, the subchronic (6 months)
      toxicity of varying levels of ulvan extracted from U. pertusa was investigated in
      Wistar rats after oral administration. ALT, ALB, ALP, WBC, PLT, and liver
      relative organ weigh of female rats showed significantly difference at 3000 mg/kg
      body weight per day, compared with control group. On the other hand, TG, T-CHO
      concentrations of female rats (6 months) were significantly decreased at 600,
      1200 and 3000 mg/kg body weight per day. This result proved that ulvan had
      antihyperlipidemic activity. Beside, ulvan showed anticoagulant activity in this
      study. Overall, our findings indicated that ulvan had affected specific
      hematology, serum biochemistry parameters and liver, and had great differences
      between males and females rats.

PMID- 24084036
TI  - Broad-spectrum activity of a novel antibiotic peptide against multidrug-resistant
      veterinary isolates.
AB  - The emergence of multidrug resistant (MDR) and extensively drug resistant (XDR)
      bacteria has become a medical and veterinary problem. Antimicrobial peptides
      (AMPs) show potential to overcome antibiotic resistance and could be used
      therapeutically. A novel AMP (AMP2041) was developed in silico and its
      microbiocidal activity against MDR clinical strains isolated from cattle (n=6),
      dogs (n=8), and pigs (n=20) was evaluated. AMP2041 showed strong antimicrobial
      activity against all Gram-positive and Gram-negative MDR clinical strains tested.
      Within 20 min of incubation, there was complete killing of Pseudomonas aeruginosa
      ATCC 27953 and a 90% reduction of colony count for Escherichia coli ATCC 25922.
      For Staphylococcus aureus ATCC 25923, a 90% reduction of colony count was
      observed within 120 min of incubation.

PMID- 24084037
TI  - Advances in the quest for virulence factors of Haemophilus parasuis.
AB  - Haemophilus parasuis colonises healthy pigs and is the aetiological agent of
      Glasser's disease. The pathogenicity of H. parasuis is poorly characterised,
      while prevention and control of Glasser's disease continues to be challenging.
      Understanding the pathogenicity of H. parasuis is essential for determining how
      this bacterium produces disease and to better distinguish between virulent and
      non-virulent strains. Infection by H. parasuis requires adhesion to and invasion
      of host cells, resistance to phagocytosis by macrophages, resistance to serum
      complement and induction of inflammation. Identification of virulence factors
      involved in these mechanisms has been limited by difficulties in producing
      mutants in H. parasuis. Recent advances in understanding the pathogenesis of H.
      parasuis are due in part to the production of deletion mutants, although most of
      the potential virulence factors described so far require further
      characterisation. Data supporting the role of lipooligosaccharide, capsule
      formation, porin proteins, cytolethal distending toxin and trimeric
      autotransporters (VtaA), among other molecules, in the virulence of H. parasuis
      have been described. This review provides an overview of the current knowledge of
      virulence factors of H. parasuis. 

PMID- 24084038
TI  - The stability of intelligence from age 11 to age 90 years: the Lothian birth
      cohort of 1921.
AB  - As a foundation for studies of human cognitive aging, it is important to know the
      stability of individual differences in cognitive ability across the life course.
      Few studies of cognitive ability have tested the same individuals in youth and
      old age. We examined the stability and concurrent and predictive validity of
      individual differences in the same intelligence test administered to the same
      individuals (the Lothian Birth Cohort of 1921, N = 106) at ages 11 and 90 years.
      The correlation of Moray House Test scores between age 11 and age 90 was .54 (.67
      when corrected for range restriction). This is a valuable foundation for
      estimating the extent to which cognitive-ability differences in very old age are
      accounted for by the lifelong stable trait and by the causes of cognitive change
      across the life course. Moray House Test scores showed strong concurrent and
      predictive validity with "gold standard" cognitive tests at ages 11 and 90. 

PMID- 24084039
TI  - How robust are probabilistic models of higher-level cognition?
AB  - An increasingly popular theory holds that the mind should be viewed as a near
      optimal or rational engine of probabilistic inference, in domains as diverse as
      word learning, pragmatics, naive physics, and predictions of the future. We argue
      that this view, often identified with Bayesian models of inference, is markedly
      less promising than widely believed, and is undermined by post hoc practices that
      merit wholesale reevaluation. We also show that the common equation between
      probabilistic and rational or optimal is not justified. 

PMID- 24084040
TI  - Paying attention to attention in recognition memory: insights from models and
      electrophysiology.
AB  - Reliance on remembered facts or events requires memory for their sources, that
      is, the contexts in which those facts or events were embedded. Understanding of
      source retrieval has been stymied by the fact that uncontrolled fluctuations of
      attention during encoding can cloud results of key importance to theoretical
      development. To address this issue, we combined electrophysiology (high-density
      electroencephalogram, EEG, recordings) with computational modeling of behavioral
      results. We manipulated subjects' attention to an auditory attribute, whether the
      source of individual study words was a male or female speaker. Posterior alpha
      band (8-14 Hz) power in subjects' EEG increased after a cue to ignore the voice
      of the person who was about to speak. Receiver-operating-characteristic analysis
      validated our interpretation of oscillatory dynamics as a marker of attention to
      source information. With attention under experimental control, computational
      modeling showed unequivocally that memory for source (male or female speaker)
      reflected a continuous signal detection process rather than a threshold
      recollection process. 

PMID- 24084041
TI  - Identification, cloning and characterization of an extracellular signal-regulated
      kinase (ERK) from Chinese shrimp, Fenneropenaeus chinensis.
AB  - Extracellular signal-regulated kinase (ERK) is a serine/threonine-specific
      protein kinase, which participates in signaling transduction pathways that
      control intracellular events, including resumption of meiosis, embryogenesis,
      cell differentiation, cell proliferation, cell death and response to radiation.
      Some virus species evolved the ability to hijack the host cell ERK signaling
      transduction pathway for viral replications and gene expressions. To obtain a
      better understanding of ERK, we cloned a cDNA encoding ERK from the muscle of
      Fenneropenaeus chinensis (FcERK). The FcERK contained a 1098 bp open reading
      frame (ORF) encoding a protein of 365 amino acid residues with a conserved
      phosphorylation motif TEY in the kinase activation loop. Pair-wise and multiple
      sequence alignment revealed that ERK is highly conserved across taxa. The FcERK
      gene expressions in the hepatopancreas and gill were noticeably higher than the
      expression observed in the muscle. A challenge test was performed to reveal the
      responses of FcERK in different tissues to white spot syndrome virus (WSSV)
      infection. Post WSSV challenge, the FcERK expression in the gill significantly
      increased during the early stage of the viral infection, the FcERK expression in
      the muscle increased later than that in the gill, and the FcERK expression in the
      hepatopancreas significantly decreased. The FcERK gene expression profile
      accorded with the results that the virus primarily infects tissues originating
      from the ectoderm, with less infection of the tissues originating from the
      mesoderm, and hardly any infection in the tissues originating from the entoderm.
      Two single nucleotide polymorphisms (SNPs) were identified in the FcERK gene,
      involving C/T transition. The SNP genotypes of two groups of shrimps,
      respectively comprising 96 WSSV-resistant shrimps and 96 WSSV-susceptible shrimps
      were obtained using a high-resolution melting (HRM) method. In the two groups,
      the MAFs of both sites were greater than 0.05, and no site departed significantly
      (P < 0.05) from HWE. The genotype distributions of both mutation sites between
      the two groups were not significantly different. These results lead to a better
      understanding of the molecular mechanisms of the host-virus interaction and
      provide useful information for disease control.

PMID- 24084042
TI  - Isolation and characterization of a c-type lysozyme from the nurse shark.
AB  - Lysozyme is a ubiquitous antibacterial enzyme that occurs in numerous
      invertebrate and vertebrate species. Three forms have been described c-type, g
      type and i-type which differ in primary structure. Shark lysozyme has not been
      characterized; here we report on the isolation and characterization of lysozyme
      from unstimulated shark (Ginglymostoma cirratum) leukocytes and provide amino
      acid sequence data across the highly conserved active site of the molecule
      identifying it to be a c-type lysozyme. A leukocyte lysate was applied either (a)
      to the first of two sequential DE-52 cellulose columns or alternatively, (b) to a
      DEAE-Sepharose column. Lysozyme activity in lysate and active fractions was
      identified by zones of lysis of Micrococcus lysodeikticus cell walls on
      lysoplates and zones of growth inhibition in agar diffusion assays using
      Planococcus citreus as the target organism. SDS-PAGE analysis revealed a 14 kDa
      protein which was identified as lysozyme by mass spectroscopic analysis of
      peptides, reactivity against anti-HEWL antibodies on a Western blot, hydrolysis
      of M. lysodeikticus cell walls, and inhibition of growth of P. citreus on AU-gel
      blots in which the area of growth inhibition correlated to a 14 kDa protein.

PMID- 24084043
TI  - Cloning, expression and functional analysis of PKR from grass carp
      (Ctenopharyngodon idellus).
AB  - The interferon-induced, dsRNA-activated protein kinase (PKR) is considered as an
      important component of innate immune system and as a representative effector
      protein of interferon system. In the present study, PKR gene (CiPKR, JX511974)
      from grass carp (Ctenopharyngodon idellus) was isolated and identified using
      homology-based PCR. CiPKR shares high sequence identity with the counterparts of
      goldfish (Crucian carp) and zebrafish (Danio rerio). The full-length cDNA of
      CiPKR was found to be 2436 bp, with an ORF of 2067 bp that encodes a polypeptide
      of 688 amino acids. The deduced polypeptide CiPKR contains three tandem dsRNA
      binding motifs (dsRBMs) at the N-terminus and a conserved Ser/Thr kinase domain
      at the C-terminus. CiPKR was expressed ubiquitously at a low-level under normal
      conditions, but it could be up-regulated after intraperitoneal (ip) injection
      with grass carp haemorrhagic virus (GCHV). CiPKR was dramatically up-regulated at
      6 h post-injection and then recovered rapidly to normal levels within 24 h;
      however, it was obviously up-regulated once again at 48 h or 72 h post-injection.
      It seemed that CiPKR could respond to GCHV infection in an IFN-independent as
      well as an IFN-dependent pathway. To further investigate its mechanism of
      biological actions, we constructed a series of recombinant plasmids including
      pcDNA3.1/PKR-wt, pcDNA3.1/PKR-K430R, pcDNA3.1/PKR-C (deletion of dsRBD sequence)
      and pcDNA3.1/PKR-C-K430R, and then each recombinant plasmid was transfected into
      CIK cells. In comparison with those of controls, a 79% and a 64% decrease of
      luciferase activities were detected in the tested cells transfected with CiPKR
      and CiPKR-C, respectively; however, luciferase activities were increased in those
      cells transfected with PKR-K430R and PKR-C-K430R, with a 160% and 115% up
      regulation, respectively. Similarly, MTT colorimetric assay indicated that cell
      viabilities of CIK cells transfected with pcDNA3.1/PKR-wt, pcDNA3.1/PKR-K430R,
      pcDNA3.1/PKR-C and pcDNA3.1/PKR-C-K430R were 49%, 90%, 54% and 100%,
      respectively. Our observations suggested that the expression of CiPKR could be up
      regulated following viral infection, and then resulted in the inhibition of
      protein synthesis and the induction of potential apoptosis.

PMID- 24084044
TI  - Digit ratio (2D:4D) and male facial attractiveness: new data and a meta-analysis.
AB  - Digit ratio (2D:4D) appears to correlate negatively with prenatal testosterone
      (T) effects in humans. As T probably increases facial masculinity, which in turn
      might be positively related to male facial attractiveness, a number of studies
      have looked into the relationship between 2D:4D and male facial attractiveness,
      showing equivocal results. Here, I present the largest and third largest samples
      so far, which investigate the relationship between 2D:4D and male facial
      attractiveness in adolescents (n = 115) and young men (n = 80). I then present
      random-effects meta-analyses of the available data (seven to eight samples,
      overall n = 362 to 469). These showed small (r ~ -.09), statistically non
      significant relationships between 2D:4D measures and male facial attractiveness.
      Thus, 2D:4D studies offer no convincing evidence at present that prenatal T has a
      positive effect on male facial attractiveness. However, a consideration of
      confidence intervals shows that, at present, a theoretically meaningful
      relationship between 2D:4D and male facial attractiveness cannot be ruled out
      either. 

PMID- 24084045
TI  - Novel fentanyl-based dual MU/delta-opioid agonists for the treatment of acute and
      chronic pain.
AB  - Approximately one third of the adult U.S. population suffers from some type of on
      going, chronic pain annually, and many more will have some type of acute pain
      associated with trauma or surgery. First-line therapies for moderate to severe
      pain include prescriptions for common mu opioid receptor agonists such as
      morphine and its various derivatives. The epidemic use, misuse and diversion of
      prescription opioids have highlighted just one of the adverse effects of mu
      opioid analgesics. Alternative approaches include novel opioids that target delta
      or kappa opioid receptors, or compounds that interact with two or more of the
      opioid receptors. AIMS: Here we report the pharmacology of a newly synthesized
      bifunctional opioid agonist (RV-Jim-C3) derived from combined structures of
      fentanyl and enkephalin in rodents. RV-Jim-C3 has high affinity binding to both
      mu and delta opioid receptors. MAIN METHODS: Mice and rats were used to test RV
      Jim-C3 in a tailflick test with and without opioid selective antagonist for
      antinociception. RV-Jim-C3 was tested for anti-inflammatory and
      antihypersensitivity effects in a model of formalin-induced flinching and spinal
      nerve ligation. To rule out motor impairment, rotarod was tested in rats. KEY
      FINDINGS: RV-Jim-C3 demonstrates potent-efficacious activity in several in vivo
      pain models including inflammatory pain, antihyperalgesia and antiallodynic with
      no significant motor impairment. SIGNIFICANCE: This is the first report of a
      fentanyl-based structure with delta and mu opioid receptor activity that exhibits
      outstanding antinociceptive efficacy in neuropathic pain, reducing the propensity
      of unwanted side effects driven by current therapies that are unifunctional mu
      opioid agonists.

PMID- 24084046
TI  - Chronic alcohol consumption, type 2 diabetes mellitus, insulin-like growth factor
      I (IGF-I), and growth hormone (GH) in ethanol-treated diabetic rats.
AB  - AIMS: Alcohol has deleterious influences on glucose metabolism which may
      contribute to the development of type 2 diabetes mellitus (T2DM). Insulin-like
      growth factor I (IGF-I) and growth hormone (GH), which interact with insulin to
      modulate metabolic control, have been shown to be related to impaired glucose
      tolerance. This study was conducted to assess the possibility that altered
      circulating IGF-I and GH levels contribute to the exacerbation of T2DM by alcohol
      use in type 2 diabetic Otsuka Long-Evans Tokushima Fatty (OLETF) rats and non
      diabetic Long-Evans Tokushima Otsuka (LETO) rats. MAIN METHOD: OLETF rats were
      pair-fed a Lieber-DeCarli Regular Ethanol diet and LETO rats were pair-fed a
      control diet for 6 weeks. At 6 weeks, an Intraperitoneal Glucose Tolerance Test
      (IP-GTT) was performed and IGF-I and GH levels were evaluated. KEY FINDINGS:
      Prior to an IP-GTT, OLETF-Ethanol (O-E) group had significantly a decrease in the
      mean glucose levels compared to OLETF-Control (O-C) group. At 120 min post IP
      GTT, the O-E group had significantly an increase in the mean glucose levels
      compared to O-C group. The serum IGF-I levels were significantly lower and the
      serum GH levels were significantly higher in the O-E group than in L-C group.
      SIGNIFICANCE: These results suggest that IGF-I and GH are prominent in defining
      the risk and development of T2DM, and may be adversely affected by heavy alcohol
      use, possibly mediating its diabetogenic effects. Thus, the overall glucose
      intolerance in the setting of alcoholism may be attributable to inappropriate
      alteration of IGF-I and GH levels.

PMID- 24084048
TI  - Bacterial recolonization of the skin and wound contamination during cardiac
      surgery.

PMID- 24084047
TI  - Distinct pharmacology and metabolism of K2 synthetic cannabinoids compared to
      Delta(9)-THC: mechanism underlying greater toxicity?
AB  - K2 or Spice products are emerging drugs of abuse that contain synthetic
      cannabinoids (SCBs). Although assumed by many teens and first time drug users to
      be a "safe" and "legal" alternative to marijuana, many recent reports indicate
      that SCBs present in K2 produce toxicity not associated with the primary
      psychoactive component of marijuana, ?(9)-tetrahydrocannabinol (Delta(9)-THC).
      This mini-review will summarize recent evidence that use of K2 products poses
      greater health risks relative to marijuana, and suggest that distinct
      pharmacological properties and metabolism of SCBs relative to Delta(9)-THC may
      contribute to the observed toxicity. Studies reviewed will indicate that in
      contrast to partial agonist properties of Delta(9)-THC typically observed in
      vitro, SCBs in K2 products act as full cannabinoid receptor type 1 (CB1R) and
      type 2 (CB2R) agonists in both cellular assays and animal studies. Furthermore,
      unlike Delta(9)-THC metabolism, several SCB metabolites retain high affinity for,
      and exhibit a range of intrinsic activities at, CB1 and CB2Rs. Finally, several
      reports indicate that although quasi-legal SCBs initially evaded detection and
      legal consequences, these presumed "advantages" have been limited by new
      legislation and development of product and human testing capabilities.
      Collectively, evidence reported in this mini-review suggests that K2 products are
      neither safe nor legal alternatives to marijuana. Instead, enhanced toxicity of
      K2 products relative to marijuana, perhaps resulting from the combined actions of
      a complex mixture of different SCBs present and their active metabolites that
      retain high affinity for CB1 and CB2Rs, highlights the inherent danger that may
      accompany use of these substances. 

PMID- 24084049
TI  - Neighborhood environment and physical activity among older adults: do the
      relationships differ by driving status?
AB  - Some attributes of neighborhood environments are associated with physical
      activity among older adults. This study examined whether the associations were
      moderated by driving status. Older adults from neighborhoods differing in
      walkability and income completed written surveys and wore accelerometers (N =
      880, mean age = 75 years, 56% women). Neighborhood environments were measured by
      geographic information systems and validated questionnaires. Driving status was
      defined on the basis of a driver's license, car ownership, and feeling
      comfortable to drive. Outcome variables included accelerometer-based physical
      activity and self-reported transport and leisure walking. Multilevel generalized
      linear regression was used. There was no significant Neighborhood Attribute *
      Driving Status interaction with objective physical activity or reported transport
      walking. For leisure walking, almost all environmental attributes were positive
      and significant among driving older adults but not among nondriving older adults
      (five significant interactions at p < .05). The findings suggest that driving
      status is likely to moderate the association between neighborhood environments
      and older adults' leisure walking.

PMID- 24084050
TI  - The role of Vitamin D level and related single nucleotide polymorphisms in
      Crohn's disease.
AB  - New Zealand has one of the highest rates of Crohn's Disease (CD) in the world,
      and there is much speculation as to why this might be. A high risk of CD has been
      associated with deficient or insufficient levels of Vitamin D (Vit D), lifestyle
      as well as various genetic polymorphisms. In this study we sought to analyse the
      relevance of serum Vit D levels, lifestyle and genotype to CD status. Serum
      samples were analysed for 25-OH-Vitamin D levels. DNA was isolated from blood and
      cheek-swabs, and Sequenom and ImmunoChip techniques were used for genotyping.
      Serum Vit D levels were significantly lower in CD patients (mean = 49.5 mg/L)
      than those found in controls (mean = 58.9 mg/L, p = 4.74 * 10-6). A total of
      seven single nucleotide polymorphisms were examined for effects on serum Vit D
      levels, with adjustment for confounding variables. Two variants: rs731236[A]
      (VDR) and rs732594[A] (SCUBE3) showed a significant association with serum Vit D
      levels in CD patients. Four variants: rs7975232[A] (VDR), rs732594[A] (SCUBE3),
      and rs2980[T] and rs2981[A] (PHF-11) showed a significant association with serum
      Vit D levels in the control group. This study demonstrates a significant
      interaction between Vit D levels and CD susceptibility, as well as a significant
      association between Vit D levels and genotype.

PMID- 24084051
TI  - Dietary magnesium intake improves insulin resistance among non-diabetic
      individuals with metabolic syndrome participating in a dietary trial.
AB  - Many cross-sectional studies show an inverse association between dietary
      magnesium and insulin resistance, but few longitudinal studies examine the
      ability to meet the Recommended Dietary Allowance (RDA) for magnesium intake
      through food and its effect on insulin resistance among participants with
      metabolic syndrome (MetS). The dietary intervention study examined this question
      in 234 individuals with MetS. Magnesium intake was assessed using 24-h dietary
      recalls at baseline, 6, and 12 months. Fasting glucose and insulin levels were
      collected at each time point; and insulin resistance was estimated by the
      homeostasis model assessment (HOMA-IR). The relation between magnesium intake and
      HOMA-IR was assessed using linear mixed models adjusted for covariates. Baseline
      magnesium intake was 287 +/- 93 mg/day (mean +/- standard deviation), and HOMA
      IR, fasting glucose and fasting insulin were 3.7 +/- 3.5, 99 +/- 13 mg/dL, and 15
      +/- 13 MUU/mL, respectively. At baseline, 6-, and 12-months, 23.5%, 30.4%, and
      27.7% met the RDA for magnesium. After multivariate adjustment, magnesium intake
      was inversely associated with metabolic biomarkers of insulin resistance (P <
      0.01). Further, the likelihood of elevated HOMA-IR (>3.6) over time was 71% lower
      [odds ratio (OR): 0.29; 95% confidence interval (CI): 0.12, 0.72] in participants
      in the highest quartile of magnesium intake than those in the lowest quartile.
      For individuals meeting the RDA for magnesium, the multivariate-adjusted OR for
      high HOMA-IR over time was 0.37 (95% CI: 0.18, 0.77). These findings indicate
      that dietary magnesium intake is inadequate among non-diabetic individuals with
      MetS and suggest that increasing dietary magnesium to meet the RDA has a
      protective effect on insulin resistance. 

PMID- 24084052
TI  - Nutrient intake values for folate during pregnancy and lactation vary widely
      around the world.
AB  - Folate is a B-vitamin with particular importance during reproduction due to its
      role in the synthesis and maintenance of DNA. Folate is well known for its role
      in preventing neural tube defects (NTDs) during the periconceptional period.
      There is also an increased need for folate throughout pregnancy to support
      optimal growth and development of the fetus and blood volume expansion and tissue
      growth of the mother. During lactation, women are at risk of folate deficiency
      due to increased demands to accommodate milk folate levels. Nutrient Intake
      Values (NIVs) for folate have been calculated to take into account additional
      needs during pregnancy and lactation. However, these values vary widely between
      countries. For example, the folate requirement that is set to meet the needs of
      almost all healthy women during pregnancy varies from 300 ug/day in the United
      Kingdom to 750 ug/day in Mexico. Currently, there is no accepted standardized
      terminology or framework for establishing NIVs. This article reviews country
      specific NIVs for folate during pregnancy and lactation and the basis for setting
      these reference values. 

PMID- 24084053
TI  - Investigation of effect of nutritional drink on chemotherapy-induced mucosal
      injury and tumor growth in an established animal model.
AB  - Chemotherapy-induced mucositis represents a significant burden to quality of life
      and healthcare costs, and may be improved through enhanced nutritional status. We
      first determined the safety of two nutritional drinks (plus placebo), and then
      potential gut protection in tumor-bearing rats in a model of methotrexate-induced
      mucositis. In study 1, animals were fed one of two test diets (or placebo or
      control chow pellets) for a total of 60 days and were monitored daily. All diets
      were found to be safe to administer. In study 2, after seven days of receiving
      diets, a Dark Agouti Mammary Adenocarcinoma (DAMA) was transplanted
      subcutaneously. Ten days after starting diets, animals had 2 mg/kg intramuscular
      methotrexate administered on two consecutive days; after this time, all animals
      were given soaked chow. Animals were monitored daily for changes in bodyweight,
      tumor burden and general health. Animals were killed 10, 12 and 16 days after
      initially starting diets, and tissues were collected at necropsy. In study 1,
      animals receiving diets had gained 0.8% and 10.8% of their starting bodyweight
      after 60 days, placebo animals 4.4%, and animals fed on standard chow had gained
      15.1%. In study 2, there was no significant influence of test diet on bodyweight,
      organ weight, tumor burden or biochemical parameters. Only animals treated with
      MTX exhibited diarrhea, although animals receiving Diet A and Diet C showed a non
      significant increase in incidence of diarrhea. Administration of these
      nutritional drinks did not improve symptoms of mucositis. 

PMID- 24084054
TI  - Risk of high dietary calcium for arterial calcification in older adults.
AB  - Concern has recently arisen about the potential adverse effects of excessive
      calcium intakes, i.e., calcium loading from supplements, on arterial
      calcification and risks of cardiovascular diseases (CVD) in older adults.
      Published reports that high calcium intakes in free-living adults have relatively
      little or no beneficial impact on bone mineral density (BMD) and fracture rates
      suggest that current recommendations of calcium for adults may be set too high.
      Because even healthy kidneys have limited capability of eliminating excessive
      calcium in the diet, the likelihood of soft-tissue calcification may increase in
      older adults who take calcium supplements, particularly in those with age or
      disease-related reduction in renal function. The maintenance of BMD and bone
      health continues to be an important goal of adequate dietary calcium consumption,
      but eliminating potential risks of CVDs from excessive calcium intakes needs to
      be factored into policy recommendations for calcium by adults. 

PMID- 24084055
TI  - Vitamin and mineral deficiencies are highly prevalent in newly diagnosed celiac
      disease patients.
AB  - Malabsorption, weight loss and vitamin/mineral-deficiencies characterize
      classical celiac disease (CD). This study aimed to assess the nutritional and
      vitamin/mineral status of current "early diagnosed" untreated adult CD-patients
      in the Netherlands. Newly diagnosed adult CD-patients were included (n = 80, 42.8
      +/- 15.1 years) and a comparable sample of 24 healthy Dutch subjects was added to
      compare vitamin concentrations. Nutritional status and serum concentrations of
      folic acid, vitamin A, B6, B12, and (25-hydroxy) D, zinc, haemoglobin (Hb) and
      ferritin were determined (before prescribing gluten free diet). Almost all CD
      patients (87%) had at least one value below the lower limit of reference.
      Specifically, for vitamin A, 7.5% of patients showed deficient levels, for
      vitamin B6 14.5%, folic acid 20%, and vitamin B12 19%. Likewise, zinc deficiency
      was observed in 67% of the CD-patients, 46% had decreased iron storage, and 32%
      had anaemia. Overall, 17% were malnourished (>10% undesired weight loss), 22% of
      the women were underweight (Body Mass Index (BMI) < 18.5), and 29% of the
      patients were overweight (BMI > 25). Vitamin deficiencies were barely seen in
      healthy controls, with the exception of vitamin B12. Vitamin/mineral deficiencies
      were counter-intuitively not associated with a (higher) grade of histological
      intestinal damage or (impaired) nutritional status. In conclusion,
      vitamin/mineral deficiencies are still common in newly "early diagnosed" CD
      patients, even though the prevalence of obesity at initial diagnosis is rising.
      Extensive nutritional assessments seem warranted to guide nutritional advices and
      follow-up in CD treatment.

PMID- 24084057
TI  - Physician roles in tactical emergency medical support: the first 20 years.
AB  - BACKGROUND: The benefits of Tactical Emergency Medical Support (TEMS) elements
      are providing injury prevention, immediate care of injuries, and medical
      augmentation of the success of dangerous law enforcement operations. TEMS is
      recognized by civilian Special Weapons and Tactics (SWAT) and various other law
      enforcement agencies around the country as a vital addition to such SWAT teams.
      The integration of specially trained TEMS personnel has become a key component of
      law enforcement special operations. OBJECTIVE: Our aim was to review the
      published literature to identify if there is a role for physicians within TEMS
      elements with regard to its establishment and progression, and to characterize
      the level of physician-specific support provided in the tactical environment for
      civilian tactical law enforcement teams. DISCUSSION: Physician presence as part
      of TEMS elements is increasing in number and popularity as the realization of the
      benefits provided by such physicians has become more apparent. The inclusion of
      physicians as active and participating members of TEMS elements is a critical
      measure to be taken for tactical law enforcement units. Physicians provide an
      added level of medical expertise to TEMS elements in rural and urban settings
      compared with law enforcement personnel with medic training. CONCLUSIONS:
      Physician involvement is an essential element of a successful TEMS program. There
      is a need for more physicians to become involved as TEMS personnel for
      specialized tactical teams to spread the time commitment and increase their
      availability to tactical units on a daily basis.

PMID- 24084058
TI  - Intentional overdose with tinzaparin: management dilemmas.
AB  - BACKGROUND: Low-molecular-weight heparin (LMWH) is increasingly being prescribed
      for prophylaxis and treatment of thromboembolic diseases. Despite the fact that
      its therapeutic use is considered to be safe, it can be complicated by major
      hemorrhage and, in contrast to unfractionated heparin, it can only partially be
      neutralized by protamine. Recent reports of LMWH overdose illustrate the need for
      a consensus on its management. OBJECTIVES: To describe a case of self-poisoning
      with a very large dose of tinzaparin and discuss management options in patients
      with LMWH overdose. CASE REPORT: A 69-year-old woman was brought to the Emergency
      Department 2 h after injecting herself with 280,000 IU of tinzaparin
      subcutaneously in an attempt to commit suicide. Despite an unrecordable activated
      partial thromboplastin time (APTT > 180 s) and prolonged prothrombin time, there
      was no evidence of active bleeding. She was given an intravenous infusion of 100
      mg protamine sulfate and was admitted to the intensive care unit, where further
      infusions of protamine were administered. Normalization of the APTT occurred 40
      50 h post admission, reflecting normal tinzaparin clearance rather than
      neutralization by protamine. No hemorrhagic complications occurred during her
      hospitalization except for prolonged bleeding from venipuncture sites.
      CONCLUSION: In this case of massive tinzaparin overdose, conventional doses of
      protamine failed to rapidly normalize the deranged coagulation parameters. The
      favorable clinical outcome suggests that, regardless of the LMWH amount injected,
      no active treatment is needed in the absence of hemorrhage. This is in accordance
      with the limited published data concerning cases of overdose with other LMWHs.

PMID- 24084056
TI  - Molecular link between vitamin D and cancer prevention.
AB  - The metabolite of vitamin D, 1alpha,25-dihydroxyvitamin D3 (also known as
      calcitriol), is a biologically active molecule required to maintain the
      physiological functions of several target tissues in the human body from
      conception to adulthood. Its molecular mode of action ranges from immediate
      nongenomic responses to longer term mechanisms that exert persistent genomic
      effects. The genomic mechanisms of vitamin D action rely on cross talk between
      1alpha,25-dihydroxyvitamin D3 signaling pathways and that of other growth factors
      or hormones that collectively regulate cell proliferation, differentiation and
      cell survival. In vitro and in vivo studies demonstrate a role for vitamin D
      (calcitriol) in modulating cellular growth and development. Vitamin D
      (calcitriol) acts as an antiproliferative agent in many tissues and significantly
      slows malignant cellular growth. Moreover, epidemiological studies have suggested
      that ultraviolet-B exposure can help reduce cancer risk and prevalence,
      indicating a potential role for vitamin D as a feasible agent to prevent cancer
      incidence and recurrence. With the preventive potential of this biologically
      active agent, we suggest that countries where cancer is on the rise--yet where
      sunlight and, hence, vitamin D may be easily acquired--adopt awareness, education
      and implementation strategies to increase supplementation with vitamin D in all
      age groups as a preventive measure to reduce cancer risk and prevalence.

PMID- 24084059
TI  - Serum immunoglobulins in the infected and convalescent phases in community
      acquired pneumonia.
AB  - BACKGROUND: A population-based case-control study was designed to assess changes
      of serum levels of immunoglobulins and IgG subclasses between infected and
      convalescent phase in community-acquired pneumonia (CAP). METHODS: Over a 2-year
      period, all subjects who were >14 years of age living in the Maresme region
      (Barcelona, Spain) diagnosed of CAP were registered. Controls were healthy
      subjects selected from the municipal census. Prognostic factors were assessed and
      serum levels of total IgG, IgA, IgM, and IgG subclasses were measured at
      diagnosis and 1 month later (cases). RESULTS: We studied 171 patients with CAP
      and 90 controls. All immunoglobulins were significantly lower in cases than in
      controls. At diagnosis, 42.7% of cases showed low levels of some immunologic
      parameter, mainly total IgG and IgG2. Low immunoglobulin levels at diagnosis were
      more frequent in patients requiring in-patient care and in those with pneumonia
      of other etiology than Streptococcus pneumoniae. In the convalescent phase, 26
      (23.6%) patients normalized immunological levels. In 27 (24.5%) cases, some
      parameter with low levels persisted especially in patients with etiology of CAP
      other than S. pneumoniae. CONCLUSIONS: Low serum levels of immunoglobulins
      particularly total IgG and IgG2 were a common finding in patients with CAP
      compared to healthy controls. Low immunoglobulin levels may be related to CAP
      prognosis and persisted in the convalescent phase in one-fourth of cases.

PMID- 24084060
TI  - Evaluation of multidimensional COPD-related subjective fatigue following a
      pulmonary rehabilitation programme.
AB  - INTRODUCTION: Subjective fatigue has been recognised as an important, multi
      component symptom in COPD. Pulmonary Rehabilitation (PR) improves fatigue
      component of the Chronic Respiratory Questionnaire, a quality of life (QoL)
      measure. However, it is not clear if all fatigue dimensions are affected equally.
      This study aims to evaluate changes in subjective multidimensional fatigue among
      people with COPD who participated in PR. METHODS: Thirty seven stable COPD
      patients were recruited; 23 patients (15 male) mean age 68.5 (range 49-86) yrs,
      mean (SD) %predicted FEV1 45.3 (19.8); completed 7 weeks of PR. Assessments (pre
      and post PR) consisted of the Multidimensional Fatigue Inventory (MFI-20), QoL
      (SGRQ), Anxiety and Depression (HADS), the London Chest Activity of Daily Living
      Scale (LCADL), muscle strength, incremental (ISWT) and endurance (ESWT) shuttle
      walk tests. The differences between pre and post PR fatigue were tested using
      Wilcoxon's test and relationships with other outcomes were examined using
      Spearman's correlation. RESULTS: There were statistically significant
      improvements in Reduced Activity (RA) (p = 0.01), General (GF) (p < 0.01) and
      Physical Fatigue (PF) (p = 0.03) components of MFI-20 after PR, but there were no
      differences in Motivation or Mental Fatigue (p > 0.05). There were significant
      improvements in ISWT (p < 0.05), ESWT (p < 0.01) and muscle strength (p = 0.03).
      Statistically significant correlations (p < 0.05) were found between changes in
      GF and in both ISWT (r = -0.43) and SGRQ impact (r = 0.46); and between RA and
      ESWT changes (r = -0.45). CONCLUSIONS: Some dimensions of fatigue in COPD are
      modifiable by a 7-week PR programme. Change in fatigue dimensions in COPD may be
      associated with a change in maximal or endurance walking distances or QoL.

PMID- 24084061
TI  - Effects of the Health Transformation Programme on tuberculosis burden in Turkey.
AB  - OBJECTIVE: The Fifty-ninth Turkish Government announced an emergency action plan
      and embarked on a comprehensive health reform named "Health Transformation
      Program" (HTP) in 2003. This study investigated the effects of HTP on
      tuberculosis (TB) burden from 2003 to 2010 in Turkey. DESIGN: TB incidence,
      prevalence, mortality and case detection rates, treatment success and direct
      observed treatment strategy (DOTS) applications rate, and contribution of these
      applications in the success of the TB war were retrospectively investigated.
      RESULTS: The annual decrease of incidence rate was 2.86 between 1995 and 2002,
      and 1.22 between and 2003 and 2010, (p < 0.05). The decrease of prevalence rate
      was 2.88 between 1995 and 2002 and 1.25 between 2003 and 2010 (p < 0.05). The
      annual declines in mortality were 0.44 between 1995 and 2002 and 0.22 between
      2003 and 2010 (p < 0.005). The DOTS application rate increased from 0% in 2003 to
      98% in 2010. After the HTP treatment success rate of TB at 85% of Turkey was
      firstly reached to 89% in 2005 and increased to 91% in 2007. Case detection rate
      of new pulmonary TB patients was 82% in 2005 and 81% in 2008 reaching the WHO
      target for the first time with HTP. CONCLUSION: A trend of reduced TB burden
      began in Turkey in 1997. As a result of the implementation of HTP beginning in
      2003, the target treatment success and DOTS application rates were achieved and
      progress has continued even in the face of the recent worldwide economic crisis.

PMID- 24084062
TI  - Effects of unilateral input and mode of hearing in the better ear: self-reported
      performance using the speech, spatial and qualities of hearing scale.
AB  - OBJECTIVE: To evaluate effects of hearing mode (normal hearing, cochlear implant,
      or hearing aid) on everyday communication among adult unilateral listeners using
      the Speech, Spatial and Qualities of Hearing Scale (SSQ). Individuals with one
      good, naturally hearing ear were expected to have higher overall ratings than
      unilateral listeners dependent on a cochlear implant or hearing aid. The authors
      anticipated that listening environments reliant on binaural processing for
      successful communication would be rated most disabling by all unilateral
      listeners. Regardless of hearing mode, all hearing-impaired participants were
      expected to have lower ratings than individuals with normal hearing bilaterally.
      A secondary objective was to compare post-treatment SSQ results of participants
      who subsequently obtained a cochlear implant for the poorer hearing ear with
      those of participants with a single normal-hearing ear. DESIGN: Participants were
      87 adults recruited as part of ongoing research investigating asymmetric hearing
      effects. Sixty-six participants were unilateral listeners who had one
      unaided/nonimplanted severe to profound hearing-loss ear and were grouped based
      on hearing mode of the better ear: 30 had one normal-hearing ear (i.e.,
      unilateral hearing-loss participants); 20 had a unilateral cochlear implant; and
      16 had a unilateral hearing aid. Data were also collected from 21 normal-hearing
      individuals, as well as a subset of participants who subsequently received a
      cochlear implant in the poorer ear and thus became bilateral listeners. Data
      analysis was completed at the domain and subscale levels. RESULTS: A significant
      mode-of-hearing group effect for the hearing-impaired participants (i.e., with
      unilateral hearing loss, unilateral cochlear implant, or unilateral hearing aid)
      was identified for two domains (Speech and Qualities) and six subscales (Speech
      in Quiet, Speech in Noise, Speech in Speech Contexts, Multiple Speech Stream
      Processing and Switching, Identification of Sound and Objects, and Sound Quality
      and Naturalness). There was no significant mode-of-hearing group effect for the
      Spatial domain or the other four subscales (Localization, Distance and Movement,
      Segregation of Sounds, and Listening Effort). Follow-up analysis indicated the
      unilateral normal-hearing ear group had significantly higher ratings than the
      unilateral cochlear implant or hearing aid groups for the Speech domain and four
      of the ten subscales; neither the cochlear implant nor hearing aid group had
      subscale ratings significantly higher than each other or the unilateral hearing
      loss group. Audibility and sound quality imparted by hearing mode were identified
      as factors related to subjective listening experience. After cochlear
      implantation to restore bilateral hearing, SSQ ratings for bilateral cochlear
      implant or cochlear implant plus hearing aid participants were significantly
      higher than those of the unilateral hearing-loss group for Speech in Quiet,
      Speech in Noise, Localization, Distance and Movement, Listening Effort, and the
      Spatial domain. Hearing-impaired individuals had significantly poorer ratings in
      all areas compared with those with bilateral normal hearing. CONCLUSIONS: Adults
      reliant on a single ear, irrespective of better ear hearing mode, including those
      with one normal hearing ear, are at a disadvantage in all aspects of everyday
      listening and communication. Audibility and hearing mode were shown to
      differentially contribute to listening experience.

PMID- 24084063
TI  - A novel application of musculoskeletal ultrasound imaging.
AB  - Ultrasound is an attractive modality for imaging muscle and tendon motion during
      dynamic tasks and can provide a complementary methodological approach for
      biomechanical studies in a clinical or laboratory setting. Towards this goal,
      methods for quantification of muscle kinematics from ultrasound imagery are being
      developed based on image processing. The temporal resolution of these methods is
      typically not sufficient for highly dynamic tasks, such as drop-landing. We
      propose a new approach that utilizes a Doppler method for quantifying muscle
      kinematics. We have developed a novel vector tissue Doppler imaging (vTDI)
      technique that can be used to measure musculoskeletal contraction velocity,
      strain and strain rate with sub-millisecond temporal resolution during dynamic
      activities using ultrasound. The goal of this preliminary study was to
      investigate the repeatability and potential applicability of the vTDI technique
      in measuring musculoskeletal velocities during a drop-landing task, in healthy
      subjects. The vTDI measurements can be performed concurrently with other
      biomechanical techniques, such as 3D motion capture for joint kinematics and
      kinetics, electromyography for timing of muscle activation and force plates for
      ground reaction force. Integration of these complementary techniques could lead
      to a better understanding of dynamic muscle function and dysfunction underlying
      the pathogenesis and pathophysiology of musculoskeletal disorders. 

PMID- 24084064
TI  - Gompertz-Makeham life expectancies: expressions and applications.
AB  - In a population of individuals, whose mortality is governed by a Gompertz-Makeham
      hazard, we derive closed-form solutions to the life-expectancy integral,
      corresponding to the cases of homogeneous and gamma-heterogeneous populations, as
      well as in the presence/absence of the Makeham term. Derived expressions contain
      special functions that aid constructing high-accuracy approximations, which can
      be used to study the elasticity of life expectancy with respect to model
      parameters. Knowledge of Gompertz-Makeham life expectancies aids constructing
      life-table exposures. 

PMID- 24084065
TI  - FMRI and fcMRI phenotypes map the genomic effect of chromosome 13 in Brown Norway
      and Dahl salt-sensitive rats.
AB  - Genes have been implicated as major contributors to many biological traits and
      susceptibility to specific diseases. However, the mechanisms of genotype action
      on central nervous system function have been elusive. It has been previously
      observed that inbred Brown Norway (BN) rats exhibit a number of quantitative
      complex traits markedly different from those of inbred Dahl salt-sensitive (SS)
      rats. These strains have become so important to cardiovascular research that a
      novel chromosome substitution approach was used to create SS and BN strains that
      have a single chromosome replaced by the homologous chromosome of the other
      strain. The present study was conducted in an effort to evaluate whether fMRI
      neuroimaging measures could be employed as a phenotype of genetic influence on
      neural biology in SS, BN, and consomic SSBN13 rat strains. Electrical forepaw
      stimulation evoked robust differential BOLD-fMRI activation along the
      thalamocortical pathway among the three strains across different stimulus
      frequencies. Moreover, using the fMRI-guided seeds in thalamus and somatosensory
      cortex for the analysis of fcMRI, we were able to characterize the strain
      specific difference in secondary somatosensory cortex, temporal association
      cortex, and the CA3 region. We were also able to define the genetic influences of
      Chr-13 on the projection and integration of sensory information in consomic SS
      13(BN) strain. We provided objective imaging evidence supporting the hypothesis
      that rat strain-specific fMRI and fcMRI combined with consomic strategy can be a
      useful tool in identifying the complex genetic divergence that is related to
      neural circuits. These findings prove the concept of neuroimaging-based
      phenotypes as a novel approach to visualize and fine-map the genetic effects onto
      brain biology at a systems level. 

PMID- 24084067
TI  - Overlapping activity periods in early visual cortex and posterior intraparietal
      area in conscious visual shape perception: a TMS study.
AB  - Parietal cortex is often activated in brain imaging studies on conscious visual
      processing, but its causal role and timing in conscious and nonconscious
      perception are poorly understood. We studied the role of posterior intraparietal
      sulcus (IPS) and early visual areas (V1/V2) in conscious and nonconscious vision
      by interfering with their functioning with MRI-guided transcranial magnetic
      stimulation (TMS). The observers made binary forced-choice decisions concerning
      the shape or color of the metacontrast masked targets and rated the quality of
      their conscious perception. TMS was applied 30, 60, 90, or 120ms after stimulus
      onset. In the shape discrimination task, TMS of V1/V2 impaired conscious
      perception at 60, 90, and 120ms and nonconscious perception at 90ms. TMS of IPS
      impaired only conscious shape perception, also around 90ms. Conscious color
      perception was facilitated or suppressed depending on the strength of the TMS
      induced electric field in V1/V2 at 90ms. The results suggest that simultaneous
      activity in V1/V2 and IPS around 90ms is necessary for visual awareness of shape
      but not for nonconscious perception. The overlapping activity periods of IPS and
      V1/V2 may reflect recurrent interaction between parietal cortex and V1 in
      conscious shape perception. 

PMID- 24084066
TI  - Function-structure associations of the brain: evidence from multimodal
      connectivity and covariance studies.
AB  - Despite significant advances in multimodal imaging techniques and analysis
      approaches, unimodal studies are still the predominant way to investigate brain
      changes or group differences, including structural magnetic resonance imaging
      (sMRI), functional MRI (fMRI), diffusion tensor imaging (DTI) and
      electroencephalography (EEG). Multimodal brain studies can be used to understand
      the complex interplay of anatomical, functional and physiological brain
      alterations or development, and to better comprehend the biological significance
      of multiple imaging measures. To examine the function-structure associations of
      the brain in a more comprehensive and integrated manner, we reviewed a number of
      multimodal studies that combined two or more functional (fMRI and/or EEG) and
      structural (sMRI and/or DTI) modalities. In this review paper, we specifically
      focused on multimodal neuroimaging studies on cognition, aging, disease and
      behavior. We also compared multiple analysis approaches, including univariate and
      multivariate methods. The possible strengths and limitations of each method are
      highlighted, which can guide readers when selecting a method based on a given
      research question. In particular, we believe that multimodal fusion approaches
      will shed further light on the neuronal mechanisms underlying the major
      structural and functional pathophysiological features of both the healthy brain
      (e.g. development) or the diseased brain (e.g. mental illness) and, in the latter
      case, may provide a more sensitive measure than unimodal imaging for disease
      classification, e.g. multimodal biomarkers, which potentially can be used to
      support clinical diagnosis based on neuroimaging techniques. 

PMID- 24084068
TI  - Revealing the neural networks associated with processing of natural social
      interaction and the related effects of actor-orientation and face-visibility.
AB  - Understanding the intentions and desires of those around us is vital for adapting
      to a dynamic social environment. In this paper, a novel event-related functional
      Magnetic Resonance Imaging (fMRI) paradigm with dynamic and natural stimuli (2s
      video clips) was developed to directly examine the neural networks associated
      with processing of gestures with social intent as compared to nonsocial intent.
      When comparing social to nonsocial gestures, increased activation in both the
      mentalizing (or theory of mind) and amygdala networks was found. As a secondary
      aim, a factor of actor-orientation was included in the paradigm to examine how
      the neural mechanisms differ with respect to personal engagement during a social
      interaction versus passively observing an interaction. Activity in the lateral
      occipital cortex and precentral gyrus was found sensitive to actor-orientation
      during social interactions. Lastly, by manipulating face-visibility we tested
      whether facial information alone is the primary driver of neural activation
      differences observed between social and nonsocial gestures. We discovered that
      activity in the posterior superior temporal sulcus (pSTS) and fusiform gyrus
      (FFG) was partially driven by observing facial expressions during social
      gestures. Altogether, using multiple factors associated with processing of
      natural social interaction, we conceptually advance our understanding of how
      social stimuli is processed in the brain and discuss the application of this
      paradigm to clinical populations where atypical social cognition is manifested as
      a key symptom. 

PMID- 24084069
TI  - Single-trial time-frequency analysis of electrocortical signals: baseline
      correction and beyond.
AB  - Event-related desynchronization (ERD) and synchronization (ERS) of
      electrocortical signals (e.g., electroencephalogram [EEG] and
      magnetoencephalogram) reflect important aspects of sensory, motor, and cognitive
      cortical processing. The detection of ERD and ERS relies on time-frequency
      decomposition of single-trial electrocortical signals, to identify significant
      stimulus-induced changes in power within specific frequency bands. Typically,
      these changes are quantified by expressing post-stimulus EEG power as a
      percentage of change relative to pre-stimulus EEG power. However, expressing post
      stimulus EEG power relative to pre-stimulus EEG power entails two important and
      surprisingly neglected issues. First, it can introduce a significant bias in the
      estimation of ERD/ERS magnitude. Second, it confuses the contribution of pre- and
      post-stimulus EEG power. Taking the human electrocortical responses elicited by
      transient nociceptive stimuli as an example, we demonstrate that expressing
      ERD/ERS as the average percentage of change calculated at single-trial level
      introduces a positive bias, resulting in an overestimation of ERS and an
      underestimation of ERD. This bias can be avoided using a single-trial baseline
      subtraction approach. Furthermore, given that the variability in ERD/ERS is not
      only dependent on the variability in post-stimulus power but also on the
      variability in pre-stimulus power, an estimation of the respective contribution
      of pre- and post-stimulus EEG variability is needed. This can be achieved using a
      multivariate linear regression (MVLR) model, which could be optimally estimated
      using partial least square (PLS) regression, to dissect and quantify the
      relationship between behavioral variables and pre- and post-stimulus EEG
      activities. In summary, combining single-trial baseline subtraction approach with
      PLS regression can be used to achieve a correct detection and quantification of
      ERD/ERS. 

PMID- 24084070
TI  - The white elephant revived: a new marriage between PET and MRI: comment to
      Cumming: "PET neuroimaging: the white elephant packs his trunk?".

PMID- 24084071
TI  - Predictors of asthma control and lung function responsiveness to step 3 therapy
      in children with uncontrolled asthma.
AB  - BACKGROUND: Predictors of improvement in asthma control and lung function to step
      3 therapy in children with persistent asthma have not been identified despite
      reported heterogeneity in responsiveness. OBJECTIVE: We sought to evaluate
      potential predictors of asthma control and lung function responsiveness to step 3
      therapy. METHODS: A post hoc analysis from the Best Add-On Giving Effective
      Response (BADGER) study tested the association between baseline biological,
      asthma control, pulmonary function, and demographic markers and responsiveness to
      step-up to a higher dose of inhaled corticosteroid (ICS step-up therapy) or
      addition of leukotriene receptor antagonist (LTRA step-up therapy) or long-acting
      beta2-agonist (LABA step-up therapy). RESULTS: In multivariate analyses higher
      impulse oscillometry reactance area was associated (P = .048) with a differential
      FEV1 response favoring LABA over ICS step-up therapy, whereas higher urinary
      leukotriene E4 levels were marginally (P = .053) related to a differential FEV1
      response favoring LTRA over LABA step-up therapy. Predictors of differential
      responses comparing ICS with LTRA step-up therapy were not apparent, probably
      because of suppression of allergic markers with low-dose ICS treatment. Minimal
      overlap was seen across FEV1 and asthma control day predictors, suggesting
      distinct mechanisms related to lung function and asthma control day responses.
      CONCLUSION: Levels of impulse oscillometry reactance area indicating peripheral
      airway obstruction and urinary leukotriene E4 levels indicating cysteinyl
      leukotriene inflammation can differentiate LABA step-up responses from responses
      to LTRA or ICS step-up therapy. Further studies with physiologic, genetic, and
      biological markers related to these phenotypes will be needed to predict
      individual responses to LABA step-up therapy.

PMID- 24084072
TI  - Predictors of response to tiotropium versus salmeterol in asthmatic adults.
AB  - BACKGROUND: Tiotropium has activity as an asthma controller. However, predictors
      of a positive response to tiotropium have not been described. OBJECTIVE: We
      sought to describe individual and differential responses of asthmatic patients to
      salmeterol and tiotropium when added to an inhaled corticosteroid, as well as
      predictors of a positive clinical response. METHODS: Data from the double-blind,
      3-way, crossover National Heart, Lung, and Blood Institute's Asthma Clinical
      Research Network's Tiotropium Bromide as an Alternative to Increased Inhaled
      Glucocorticoid in Patients Inadequately Controlled on a Lower Dose of Inhaled
      Corticosteroid (ClinicalTrials.gov number, NCT00565266) trial were analyzed for
      individual and differential treatment responses to salmeterol and tiotropium and
      predictors of a positive response to the end points FEV1, morning peak expiratory
      flow (PEF), and asthma control days (ACDs). RESULTS: Although approximately equal
      numbers of patients showed a differential response to salmeterol and tiotropium
      in terms of morning PEF (n = 90 and 78, respectively) and ACDs (n = 49 and 53,
      respectively), more showed a differential response to tiotropium for FEV1 (n =
      104) than salmeterol (n = 62). An acute response to a short-acting
      bronchodilator, especially albuterol, predicted a positive clinical response to
      tiotropium for FEV1 (odds ratio, 4.08; 95% CI, 2.00-8.31; P < .001) and morning
      PEF (odds ratio, 2.12; 95% CI, 1.12-4.01; P = 0.021), as did a decreased
      FEV1/forced vital capacity ratio (FEV1 response increased 0.39% of baseline for
      every 1% decrease in FEV1/forced vital capacity ratio). Higher cholinergic tone
      was also a predictor, whereas ethnicity, sex, atopy, IgE level, sputum eosinophil
      count, fraction of exhaled nitric oxide, asthma duration, and body mass index
      were not. CONCLUSION: Although these results require confirmation, predictors of
      a positive clinical response to tiotropium include a positive response to
      albuterol and airway obstruction, factors that could help identify appropriate
      patients for this therapy.

PMID- 24084073
TI  - Suppressor of cytokine signaling 3 expression is diminished in sinonasal tissues
      from patients with chronic rhinosinusitis with nasal polyps.

PMID- 24084074
TI  - Tmem79/Matt is the matted mouse gene and is a predisposing gene for atopic
      dermatitis in human subjects.
AB  - BACKGROUND: Atopic dermatitis (AD) is a major inflammatory condition of the skin
      caused by inherited skin barrier deficiency, with mutations in the filaggrin gene
      predisposing to development of AD. Support for barrier deficiency initiating AD
      came from flaky tail mice, which have a frameshift mutation in Flg and also carry
      an unknown gene, matted, causing a matted hair phenotype. OBJECTIVE: We sought to
      identify the matted mutant gene in mice and further define whether mutations in
      the human gene were associated with AD. METHODS: A mouse genetics approach was
      used to separate the matted and Flg mutations to produce congenic single-mutant
      strains for genetic and immunologic analysis. Next-generation sequencing was used
      to identify the matted gene. Five independently recruited AD case collections
      were analyzed to define associations between single nucleotide polymorphisms
      (SNPs) in the human gene and AD. RESULTS: The matted phenotype in flaky tail mice
      is due to a mutation in the Tmem79/Matt gene, with no expression of the encoded
      protein mattrin in the skin of mutant mice. Matt(ft) mice spontaneously have
      dermatitis and atopy caused by a defective skin barrier, with mutant mice having
      systemic sensitization after cutaneous challenge with house dust mite allergens.
      Meta-analysis of 4,245 AD cases and 10,558 population-matched control subjects
      showed that a missense SNP, rs6684514, [corrected] in the human MATT gene has a
      small but significant association with AD. CONCLUSION: In mice mutations in Matt
      cause a defective skin barrier and spontaneous dermatitis and atopy. A common SNP
      in MATT has an association with AD in human subjects.

PMID- 24084076
TI  - Tolerance of baked milk in patients with cow's milk-mediated eosinophilic
      esophagitis.

PMID- 24084075
TI  - The biology of the glucocorticoid receptor: new signaling mechanisms in health
      and disease.
AB  - Glucocorticoids are primary stress hormones necessary for life that regulate
      numerous physiologic processes in an effort to maintain homeostasis. Synthetic
      derivatives of these hormones have been mainstays in the clinic for treating
      inflammatory diseases, autoimmune disorders, and hematologic cancers. The
      physiologic and pharmacologic actions of glucocorticoids are mediated by the
      glucocorticoid receptor (GR), a member of the nuclear receptor superfamily of
      ligand-dependent transcription factors. Ligand-occupied GR induces or represses
      the transcription of thousands of genes through direct binding to DNA response
      elements, physically associating with other transcription factors, or both. The
      traditional view that glucocorticoids act through a single GR protein has changed
      dramatically with the discovery of a large cohort of receptor isoforms with
      unique expression, gene-regulatory, and functional profiles. These GR subtypes
      are derived from a single gene by means of alternative splicing and alternative
      translation initiation mechanisms. Posttranslational modification of these GR
      isoforms further expands the diversity of glucocorticoid responses. Here we
      discuss the origin and molecular properties of the GR isoforms and their
      contribution to the specificity and sensitivity of glucocorticoid signaling in
      healthy and diseased tissues. 

PMID- 24084077
TI  - Does BCG vaccination protect against childhood asthma? Final results from the
      Manchester Community Asthma Study retrospective cohort study and updated
      systematic review and meta-analysis.
AB  - BACKGROUND: The Manchester Community Asthma Study (MANCAS) found a protective
      effect against the risk of wheeze at age 6 to 11 years for children given
      neonatal BCG vaccination. Our subsequent systematic review and meta-analysis
      suggested that BCG vaccination did not protect against allergic sensitization but
      might have exerted a protective effect against nonatopic asthma. OBJECTIVES: We
      sought to assess whether the protective effect of BCG vaccination on wheeze
      observed in the MANCAS cohort was maintained at age 13 to 17 years and to
      incorporate the findings from this final MANCAS analysis into an updated
      systematic review and meta-analysis. METHODS: BCG vaccination status was
      determined from health records and respiratory outcomes from questionnaire
      responses. We updated the systematic review and used fixed-effects and random
      effects modeling to undertake meta-analyses. RESULTS: There were 1608
      participants in the final MANCAS analysis. The 12-month prevalence of wheeze was
      15.1%. There was no difference in prevalence between those who were and were not
      BCG vaccinated (15.8% vs 14.3%; relative risk, 1.05; 95% CI, 0.94-1.19). The
      updated meta-analysis incorporated 4 new studies: this showed that the protective
      effect of BCG vaccination against the development of asthma identified in our
      previous meta-analysis was attenuated (odds ratio, 0.95; 95% CI, 0.89-1.00). No
      protective effect of BCG was seen for sensitization, eczema/atopic dermatitis,
      rhinoconjunctivitis, or allergy in general. CONCLUSIONS: Taken together, the
      final results of the MANCAS cohort and the updated systematic review and meta
      analysis provide clearer evidence that any protective effect of BCG vaccination
      on childhood asthma is likely to be transient.

PMID- 24084079
TI  - The role of Tenascin C in the lymphoid progenitor cell niche.
AB  - Hemopoietic stem cells (HSCs) are extrinsically controlled by the bone marrow
      (BM) microenvironment. Mice devoid of the extracellular matrix molecule Tenascin
      C (TNC) were reported to develop normally. The current study explores the
      relationship between TNC and hemopoiesis, from HSCs within their niche to
      maturing progenitors in alternate niches. Although the absence of TNC did not
      alter the size of the BM stem cell pool, we report decreased thymic T cell
      progenitors with redistribution to other lymphoid organs, suggesting an anchoring
      role for TNC. TNC did not play an essential role in stem and progenitor cell
      homing to BM, but significantly altered lymphoid primed progenitor cell homing.
      These cells express the TNC receptor, integrin alpha9beta1, with the same reduced
      homing evident in the absence of this integrin. The absence of TNC also resulted
      in an increased proportion and number of mature circulating T cells. In addition,
      the absence of TNC significantly impaired hemopoietic reconstitution after
      transplant and increased stem and progenitor cell mobilization. In summary, our
      analysis revealed unidentified roles for TNC in hemopoiesis: in lineage
      commitment of thymic T cell progenitors, peripheral T cell migration, and
      hemopoietic reconstitution. 

PMID- 24084080
TI  - Differential IRAK signaling in hematologic malignancies.

PMID- 24084078
TI  - A molecular perspective on TH2-promoting cytokine receptors in patients with
      allergic disease.
AB  - The cytokines IL-4, IL-13, and thymic stromal lymphopoietin play a key role in
      allergic disease by virtue of their ability to initiate, maintain, and augment
      TH2 responses. These molecules mediate their effects through type 1 cytokine
      receptors, which bind cytokines with a characteristic structure. Receptors are
      expressed on a broad array of immune cell types and are integral to complex
      cytokine networks operating in health and disease. TH2-promoting cytokines bind
      different configurations of receptors. Receptor subunits can exist in surface
      bound or soluble forms, as well as in isolation or in partnership with other
      subunits. Sharing of receptor subunits among different cytokine receptor
      complexes adds to the intricate landscape. This article describes the
      characteristics of receptors for IL-4, IL-13, and thymic stromal lymphopoietin
      and their respective ligands from a structure-function perspective. We detail the
      mechanisms of receptor complex assembly, the interrelated nature of these
      receptors, and the effect on allergic inflammation. The ability for novel and
      atypical types of receptors to modulate inflammatory processes is also discussed.
      We highlight current and emerging treatments that target TH2-promoting receptor
      complexes. Understanding the molecular features of these receptors provides
      insight into different disease phenotypes and the variable clinical outcomes
      arising from targeted therapies. These considerations can be used to inform
      future directions for research and creative strategies for treating individual
      patients.

PMID- 24084081
TI  - Programmable folding of fusion RNA in vivo and in vitro driven by pRNA 3WJ motif
      of phi29 DNA packaging motor.
AB  - Misfolding and associated loss of function are common problems in constructing
      fusion RNA complexes due to changes in energy landscape and the nearest-neighbor
      principle. Here we report the incorporation and application of the pRNA-3WJ motif
      of the phi29 DNA packaging motor into fusion RNA with controllable and
      predictable folding. The motif included three discontinuous ~18 nucleotide (nt)
      fragments, displayed a distinct low folding energy (Shu D et al., Nature
      Nanotechnology, 2011, 6:658-667), and folded spontaneously into a leading core
      that enabled the correct folding of other functionalities fused to the RNA
      complex. Three individual fragments dispersed at any location within the sequence
      allowed the other RNA functional modules to fold into their original structures
      with authentic functions, as tested by Hepatitis B virus ribozyme, siRNA, and
      aptamers for malachite green (MG), spinach, and streptavidin (STV). Only nine
      complementary nucleotides were present for any two of the three ~18-nt fragments,
      but the three 9 bp branches were so powerful that they disrupted other double
      strands with more than 15 bp within the fusion RNA. This system enabled the
      production of fusion complexes harboring multiple RNA functionalities with
      correct folding for potential applications in biotechnology, nanomedicine and
      nanotechnology. We also applied this system to investigate the principles
      governing the folding of RNA in vivo and in vitro. Temporal production of RNA
      sequences during in vivo transcription caused RNA to fold into different
      conformations that could not be predicted with routine principles derived from in
      vitro studies. 

PMID- 24084082
TI  - The differential extension in dsDNA bound to Rad51 filaments may play important
      roles in homology recognition and strand exchange.
AB  - RecA and Rad51 proteins play an important role in DNA repair and homologous
      recombination. For RecA, X-ray structure information and single molecule force
      experiments have indicated that the differential extension between the
      complementary strand and its Watson-Crick pairing partners promotes the rapid
      unbinding of non-homologous dsDNA and drives strand exchange forward for
      homologous dsDNA. In this work we find that both effects are also present in
      Rad51 protein. In particular, pulling on the opposite termini (3' and 5') of one
      of the two DNA strands in a dsDNA molecule allows dsDNA to extend along non
      homologous Rad51-ssDNA filaments and remain stably bound in the extended state,
      but pulling on the 3'5' ends of the complementary strand reduces the strand
      exchange rate for homologous filaments. Thus, the results suggest that
      differential extension is also present in dsDNA bound to Rad51. The differential
      extension promotes rapid recognition by driving the swift unbinding of dsDNA from
      non-homologous Rad51-ssDNA filaments, while at the same time, reducing base pair
      tension due to the transfer of the Watson-Crick pairing of the complementary
      strand bases from the highly extended outgoing strand to the slightly less
      extended incoming strand, which drives strand exchange forward. 

PMID- 24084083
TI  - The active site of TthPolX is adapted to prevent 8-oxo-dGTP misincorporation.
AB  - Full genome sequencing of bacterial genomes has revealed the presence of numerous
      genes encoding family X DNA polymerases. These enzymes play a variety of
      biological roles and, accordingly, display often striking functional differences.
      Here we report that the PolX from the heat-stable organism Thermus thermophilus
      (TthPolX) inserts the four dNTPs with strong asymmetry. We demonstrate that this
      behaviour is related to the presence of a single divergent residue in the active
      site of TthPolX. Mutation of this residue (Ser(266)) to asparagine, the residue
      present in most PolXs, had a strong effect on TthPolX polymerase activity,
      increasing and equilibrating the insertion efficiencies of the 4 dNTPs. Moreover,
      we show that this behaviour correlates with the ability of TthPolX to insert 8
      oxo-dGMP. Although the wild-type enzyme inefficiently incorporates 8-oxo-dGMP,
      the substitution of Ser(266) to asparagine resulted in a dramatic increase in 8
      oxo-dGMP incorporation opposite dA. These results suggest that the presence of a
      serine at position 266 in TthPolX allows the enzyme to minimize the formation of
      dA:8-oxo-dGMP at the expense of decreasing the insertion rate of pyrimidines. We
      discuss the structural basis for these effects and the implications of this
      behaviour for the GO system (BER of 8-oxo-dG lesions). 

PMID- 24084085
TI  - Use of tissue expander in pelvic Ewing's sarcoma treated with radiotherapy.
AB  - INTRODUCTION: The local treatment option for pelvic Ewing sarcoma (ES) remains
      uncertain and challenging as surgery is often disabling while radiotherapy alone
      has a higher risk of local recurrence but not necessarily a worse survival. The
      aim is to analyse the outcome of patients with pelvic ES after radiotherapy as
      the primary local treatment in combination with a temporary intrapelvic
      surgically placed tissue expander (TE) to reduce bowel complications. MATERIALS
      AND METHODS: 20 patients were retrospectively analysed. All patients had
      neoadjuvant and adjuvant chemotherapy. We identified survival, time to develop
      local recurrence and metastasis, dose of radiotherapy administered, local
      complications related to the use of the tissue expander and bowel effects of
      radiotherapy. RESULTS: The median follow-up was 41 months. 14 patients were stage
      IIb and six stage III. There were no problems after insertion of the TE and only
      one patient who developed mild diarrhoea. Local recurrence occurred in six
      patients. At the last follow-up 12 patients have died from sarcoma, five are
      disease free and three have had recurrent disease. CONCLUSIONS: In this paper we
      reviewed pelvic Ewing sarcoma with all the special considerations that this
      entails. We think that tissue expander can be safely used when radiotherapy is
      chosen to treat pelvic ES. It does appear to prevent bowel problems and is a low
      morbidity procedure. New treatment approaches should be considered to give a
      chance of cure to those patients with "bad prognostic" pelvic ES.

PMID- 24084084
TI  - The immediate upstream region of the 5'-UTR from the AUG start codon has a
      pronounced effect on the translational efficiency in Arabidopsis thaliana.
AB  - The nucleotide sequence around the translational initiation site is an important
      cis-acting element for post-transcriptional regulation. However, it has not been
      fully understood how the sequence context at the 5'-untranslated region (5'-UTR)
      affects the translational efficiency of individual mRNAs. In this study, we
      provide evidence that the 5'-UTRs of Arabidopsis genes showing a great difference
      in the nucleotide sequence vary greatly in translational efficiency with more
      than a 200-fold difference. Of the four types of nucleotides, the A residue was
      the most favourable nucleotide from positions -1 to -21 of the 5'-UTRs in
      Arabidopsis genes. In particular, the A residue in the 5'-UTR from positions -1
      to -5 was required for a high-level translational efficiency. In contrast, the T
      residue in the 5'-UTR from positions -1 to -5 was the least favourable nucleotide
      in translational efficiency. Furthermore, the effect of the sequence context in
      the -1 to -21 region of the 5'-UTR was conserved in different plant species.
      Based on these observations, we propose that the sequence context immediately
      upstream of the AUG initiation codon plays a crucial role in determining the
      translational efficiency of plant genes. 

PMID- 24084086
TI  - Transferring innovative freehand SPECT to the operating room: first experiences
      with sentinel lymph node biopsy in malignant melanoma.
AB  - PURPOSE: The purpose of this study was to report on the first experiences with
      freehand single-photon emission-computed tomography (freehand SPECT) in sentinel
      lymph node biopsy (SLNB) in patients with malignant melanoma. Freehand SPECT is a
      novel imaging modality combining gamma probes, surgical navigation systems, and
      emission tomography algorithms, designed to overcome some of the limitations of
      conventional gamma probes. METHODS: In this study 20 patients with malignant
      melanoma underwent conventional planar scintigraphy prior to surgery. In the
      operating room, the number and location of separable SLNs were detected first by
      a pre-incisional scan with freehand SPECT to render a 3D-image of the target site
      and afterwards by a scan with a conventional gamma probe. After SLNB another scan
      was performed to document the removal of all targeted SLNs. RESULTS: Planar
      scintigraphy identified 40 SLNs in 26 nodal basins. Pre-incisional freehand SPECT
      mapped 38 of these nodes as well as one additional node in one patient (95.0%
      node based sensitivity). The results of freehand SPECT were identical to those of
      planar scintigraphy in 25 basins, while it missed one basin (96.2% basin based
      sensitivity). In comparison, the gamma probe failed to detect 7 nodes in 4 basins
      (82.5% node based sensitivity and 84.6% basin based sensitivity). After resection
      freehand SPECT detected 9 remaining radioactive spots, two of whichwere resected
      as they matched the position of SLNs detected on preoperative planar
      scintigraphy. CONCLUSIONS: Freehand SPECT provides a real-time, intraoperative 3D
      image of the radioactive labelled SLNs, facilitating their detection and
      resection.

PMID- 24084087
TI  - Impact of hepatectomy margin on survival following resection of colorectal
      metastasis: the role of adjuvant therapy and its effects.
AB  - INTRODUCTION: The optimal width of microscopic margin and the use of adjuvant
      therapy after a positive margin for hepatic resection for colorectal liver
      metastasis (CRCLM) has not been conclusively determined. The aim of the current
      study is to evaluate the influence of width of surgical margin and adjunctive
      therapy upon disease free and overall survival. METHODS: All patients undergoing
      hepatectomy for CRCLM from 1997 to 2012 were identified from a prospectively
      maintained, IRB approved database. Patients were divided into four subgroups
      based on the parenchymal margin: positive, <0.1 cm, 0.1 cm-1 cm, and >1 cm.
      RESULTS: A total of 373 patients were included for analysis with a median follow
      up of 26 months (range 9-103 months) and a median overall survival of 53 months.
      The resection margin was positive (26 patients median OS 24 months), <0.1 cm (48
      patients median OS 36 mon), 0.1 cm-1 cm (82 patients median OS 44 months), and >1
      cm (217 patients median OS 64 months). The most common adjunctive therapy was
      chemotherapy, hepatic arterial therapy, or local. Patients with positive margins
      also had the shortest disease free survival (DFS), 16 months. The DFS was similar
      amongst the other margin groups (<0.1 cm: 21 months, 0.1-1 cm: 22 months, >1 cm
      25 months). Hepatectomy margin independently influenced survival (p = 0.017) and
      disease free survival (p = 0.034). Patients with negative margins has similar
      overall recurrence rates (p = 0.36) and survival rates (p = 0.89). CONCLUSIONS: A
      positive surgical margin indicates a worse overall biology of disease for
      patients undergoing hepatectomy for CRCLM, and appropriate multi-disciplinary
      therapy should be considered in this high risk patient population. Marginal width
      if a complete resection has been achieved does not adversely effect overall
      surgical in patients with CRCLM.

PMID- 24084088
TI  - Does intravenous fish oil benefit patients post-surgery? A meta-analysis of
      randomised controlled trials.
AB  - BACKGROUND AND AIMS: Supplementation of fish oil (FO) containing lipid emulsions
      has been associated with a reduction in the length of hospital stay, infections
      and liver dysfunction in patients undergoing major surgery. We carried out a meta
      analysis and subgroup analysis to examine randomised clinical trial (RCT)-based
      evidence of the aforementioned effects. METHODS: Four databases, reference lists
      and the WHO ICTRP were systematically searched for RCTs to access the clinical
      efficacy of fish oil-enriched total parenteral nutrition in post-surgery
      patients. Methodological quality assessment was based on the Cochrane Handbook
      and GRADE. RESULTS: Twenty-one RCTs were enrolled for meta-analysis. FO was
      associated with a significant reduction in the length of hospital stay (mean = 
      2.14 d, 95% CI = -3.02 to -1.27), infections (OR = 0.53, 95% CI = 0.35-0.81), ALT
      (mean = -6.35 U/L, 95% CI = -11.75 to -0.94), GGT (mean = -11.01 U/L, 95% CI = 
      20.77 to -1.25) and total bilirubin (mean = -2.06 MUmol/L, 95% CI = -3.6 to 
      0.52), as well as a non-significant change in mortality and postoperative medical
      cost. The quality of evidence of each clinical outcome was accessed as high.
      CONCLUSION: FO-enriched lipid emulsions are likely to reduce infections, the
      length of hospital stay and liver dysfunction without influencing mortality and
      may be a safe and preferable choice in post-surgery patients. Further well
      designed trials should be performed to determine whether FO lipid emulsions
      reduce mortality in patients undergoing hepatic surgery, especially liver
      transplantation, and the cost effectiveness of such treatment.

PMID- 24084089
TI  - Fully automatic software for retinal thickness in eyes with diabetic macular
      edema from images acquired by cirrus and spectralis systems.
AB  - PURPOSE: To determine whether a novel automatic segmentation program, the Duke
      Optical Coherence Tomography Retinal Analysis Program (DOCTRAP), can be applied
      to spectral-domain optical coherence tomography (SD-OCT) images obtained from
      different commercially available SD-OCT in eyes with diabetic macular edema
      (DME). METHODS: A novel segmentation framework was used to segment the retina,
      inner retinal pigment epithelium, and Bruch's membrane on images from eyes with
      DME acquired by one of two SD-OCT systems, Spectralis or Cirrus high definition
      (HD)-OCT. Thickness data obtained by the DOCTRAP software were compared with
      those produced by Spectralis and Cirrus. Measurement agreement and its dependence
      were assessed using intraclass correlation (ICC). RESULTS: A total of 40 SD-OCT
      scans from 20 subjects for each machine were included in the analysis.
      Spectralis: the mean thickness in the 1-mm central area determined by DOCTRAP and
      Spectralis was 463.8 +/- 107.5 MUm and 467.0 +/- 108.1 MUm, respectively (ICC,
      0.999). There was also a high level agreement in surrounding areas (out to 3 mm).
      Cirrus: the mean thickness in the 1-mm central area was 440.8 +/- 183.4 MUm and
      442.7 +/- 182.4 MUm by DOCTRAP and Cirrus, respectively (ICC, 0.999). The
      thickness agreement in surrounding areas (out to 3 mm) was more variable due to
      Cirrus segmentation errors in one subject (ICC, 0.734-0.999). After manual
      correction of the errors, there was a high level of thickness agreement in
      surrounding areas (ICC, 0.997-1.000). CONCLUSIONS: The DOCTRAP may be useful to
      compare retinal thicknesses in eyes with DME across OCT platforms.

PMID- 24084090
TI  - Apoptotic photoreceptor loss and altered expression of lysosomal proteins in the
      nclf mouse model of neuronal ceroid lipofuscinosis.
AB  - PURPOSE: Mutations in the CLN6 gene cause variant late-infantile neuronal ceroid
      lipofuscinosis, a lysosomal storage disorder clinically characterized by
      progressive loss of vision, dementia, seizures, and early death. Here, we
      analyzed the time course of photoreceptor loss and the role of lysosomes in nclf
      mice, an animal model of the human CLN6 disease. METHODS: Labeling of apoptotic
      cells, activated astrocytes, and Muller cells, and expression analyses of glial
      fibrillary acidic protein, rhodopsin, and lysosomal proteins were performed on
      nclf mice during the course of retinal degeneration. In addition, the
      distribution and variability of storage material was examined at the
      ultrastructural level. RESULTS: Progressive apoptotic loss of photoreceptor cells
      was observed in nclf mice, resulting in reduction of the outer nuclear layer to
      approximately 3 rows of photoreceptor cells at 9 months of age. Onset of reactive
      gliosis was observed in 1-month-old nclf mice. Ultrastructural analysis revealed
      lysosomal storage material containing curvilinear and fingerprint-like inclusions
      in various retinal cell types. Expression levels of soluble mannose 6-phosphate
      containing lysosomal enzymes, such as cathepsin D and the lysosomal membrane
      protein Lamp1, were increased in retinal cells of nclf mice. CONCLUSIONS:
      Accumulation of heterogeneous nondegraded macromolecules in dysfunctional
      lysosomes and autolysosomes impairs photoreceptor cells, ultimately leading to
      early-onset apoptotic death with subsequent activation of astrocytes and Muller
      cells in the retina of nclf mice. The defined steps of photoreceptor degeneration
      suggest that nclf mice might serve as an ideal animal model for experimental
      therapeutic approaches aimed at attenuating vision loss in neuronal ceroid
      lipofuscinosis.

PMID- 24084091
TI  - Migration of retinal pigment epithelium cells is regulated by protein kinase
      Calpha in vitro.
AB  - PURPOSE: Retinal pigment epithelium (RPE) cell migration and proliferation are
      considered key elements in proliferative vitreoretinopathy (PVR). Downregulation
      of protein kinase Calpha (PKCalpha) can inhibit RPE cell proliferation. Here, we
      sought to analyze whether PKCalpha affects the migration of RPE cells. METHODS:
      Human RPE (hRPE) cells were cultured, confirmed by immunofluorescence staining,
      and divided into four groups: control, thymeleatoxin, non-small interfering RNA
      (siRNA), and siRNA-PKCalpha. Thymeleatoxin was used to activate PKCalpha, and
      siRNA-PKCalpha was used to knock it down. Expression of PKCalpha was confirmed by
      quantitative RT-PCR (qRT-PCR). Cell migration ability was analyzed by wound
      healing assay and transwell chamber assay. Expression of zonula occludens (ZO)-1
      and occludin was determined by immunofluorescence. RESULTS: Pure populations of
      hRPE cell cultures were observed using light and fluorescence microscopy. The
      mRNA levels of PKCalpha were not significantly increased by thymeleatoxin, but
      were reduced by siRNA-PKCalpha as determined by qRT-PCR assay. The wound healed
      faster in the thymeleatoxin group than in the control group at time points 12,
      15, and 20 hours. The wound healed more slowly in the siRNA-PKCalpha group than
      in the non-siRNA group at the three time points. A similar tendency among the
      four groups was consistently observed in regard to cell numbers counted in the
      transwell chamber assay. The expression of ZO-1 was highest in the siRNA-PKCalpha
      group, similar in the control and non-siRNA groups, and lowest in the
      thymeleatoxin group. After migration, the fluorescence intensity of ZO-1 was
      reduced to similarly weak levels among the four groups. CONCLUSIONS: Retinal
      pigment epithelium cell migration is enhanced by a PKCalpha agonist and
      suppressed by a PKCalpha antagonist. The results suggest that a PKCalpha-mediated
      signal transduction pathway plays a crucial role in hRPE cell migration and may
      be a potential therapeutic target against hRPE cell migration and PVR disease.

PMID- 24084092
TI  - VEGF rescues cigarette smoking-induced human RPE cell death by increasing
      autophagic flux: implications of the role of autophagy in advanced age-related
      macular degeneration.
AB  - PURPOSE: Cigarette smoking (CS) is the most consistent risk factor for advanced
      age-related macular degeneration (AMD). To verify the molecular basis for CS
      induced RPE alterations, RPE cell survival levels after being exposed to CS in
      relation with VEGF expression and autophagic flux were evaluated. METHODS:
      Cigarette smoking extract (CSE) was added to ARPE-19 cells and hydrogen peroxide
      (HP) was used as a pure oxidant control. Cell survival was measured by flow
      cytometry with annexin V-fluorescein isothiocyanate. Cell survival analysis was
      performed after pretreatment with anti-VEGF or recombinant VEGF. The expression
      of VEGF-A, VEGF-R1/R2, and soluble VEGF-R1 was determined by semiquantitative RT
      PCR. LC3B-I (microtubule-associated protein-1 inhibitors), LC3B-II, and
      phosphorylation of Akt or Erk were measured with Western blot. Autophagic flux
      was determined by increasing LC3B-II levels with inhibitors of lysosomal
      proteases. RESULTS: Incubation with 5% CSE for 16 hours induced approximately 30%
      cell death, which was similar to cell death levels when exposed to concentrations
      of 200 MUM HP. Pretreatment with anti-VEGF did not decrease cell survival under
      CSE, unlike the decrease in cell survival shown with HP. However, supplementation
      with VEGF rescued CSE-induced RPE cell death. Interestingly, CSE caused an
      increase in autophagic flux, which was augmented with VEGF pretreatment.
      Cigarette smoking extract also degraded the total amounts of Akt levels, and VEGF
      blunted CSE-induced phosphorylation of Erk. CONCLUSIONS: Cigarette smoking
      extract, similar to HP, affects cell viability and induces expression of VEGF and
      its receptors. Increased autophagic flux accelerated by treatment of exogenous
      VEGF may have a role in rescuing CSE-induced RPE cell death.

PMID- 24084093
TI  - Ultrastructural localization of GPR179 and the impact of mutant forms on retinal
      function in CSNB1 patients and a mouse model.
AB  - PURPOSE: Complete congenital stationary night blindness (CSNB1) is characterized
      by loss of night vision due to a defect in the retinal ON-bipolar cells (BCs).
      Mutations in GPR179, encoding the G-protein-coupled receptor 179, have been found
      in CSNB1 patients. In the mouse, GPR179 is localized to the tips of ON-BC
      dendrites. In this study we determined the ultrastructural localization of GPR179
      in human retina and determined the functional consequences of mutations in GPR179
      in patients and mice. METHODS: The localization of GRP179 was analyzed in
      postmortem human retinas with immunohistochemistry. The functional consequences
      of the loss of GPR179 were analyzed with standard and 15-Hz flicker ERG
      protocols. RESULTS: In the human retina, GPR179 is localized on the tips of ON-BC
      dendrites, which invaginate photoreceptors and terminate juxtaposed to the
      synaptic ribbon. The 15-Hz flicker ERG abnormalities found in patients with
      mutations in GPR179 more closely resemble those from patients with mutations in
      either TRPM1 or NYX than in GRM6. 15-Hz flicker ERG abnormalities of Gpr179(nob5)
      and Grm6(nob3) mice were comparable. CONCLUSIONS: GRP179 is expressed on
      dendrites of ON-BCs, indicating that GRP179 is involved in the ON-BCs' signaling
      cascade. The similarities of 15-Hz flicker ERGs noted in GPR179 patients and NYX
      or TRPM1 patients suggest that the loss of GPR179 leads to the loss or closure of
      TRPM1 channels. The difference between the 15-Hz flicker ERGs of mice and humans
      indicates the presence of important species differences in the retinal activity
      that this signal represents.

PMID- 24084094
TI  - Standardized baseline human corneal subbasal nerve density for clinical
      investigations with laser-scanning in vivo confocal microscopy.
AB  - PURPOSE: We established a baseline value for central corneal subbasal nerve
      density in a large, healthy cohort. METHODS: A total of 106 healthy volunteers
      (207 eyes) underwent full ophthalmic examination, including laser-scanning in
      vivo confocal microscopy (IVCM) of the central cornea. Images of the corneal
      subbasal nerve plexus were acquired and analyzed based on defined criteria. Nerve
      tracing was performed by two human observers and by a fully automated method.
      Subbasal nerve density was stratified by eye, observer, tracing method,
      calculation method, and age group. Association of nerve density with age was
      examined by linear regression and population distribution was examined by
      nonlinear regression. RESULTS: We analyzed 892 distinct, high quality images of
      the subbasal nerve plexus (mean, 4.3 images/eye) from 207 eyes. An overall mean
      central subbasal nerve density of 19 mm/mm(2) was found in 106 subjects aged 15
      to 88 years, independent of eye, sex, or nerve tracing method, while the SD was a
      consistent 4 to 5 mm/mm(2). Subbasal nerve density followed a normal Gaussian
      distribution, and correlated negatively with age, with a mean decline of 0.25% to
      0.30% per year, independent of eye, observer, or nerve tracing method. Moreover,
      the use of automated tracing techniques and randomized sampling may improve the
      speed and reproducibility of subbasal nerve density assessment for clinical
      applications. CONCLUSIONS: A baseline human corneal subbasal nerve density has
      been determined by laser-scanning IVCM using rigorous methods. The methods and
      results could aid in the future assessment of corneal nerves in various patient
      populations.

PMID- 24084095
TI  - Functional characterization and multimodal imaging of treatment-naive "quiescent"
      choroidal neovascularization.
AB  - PURPOSE: To investigate the multimodal morphological and functional
      characteristics of treatment-naive "quiescent" choroidal neovascularization (CNV)
      secondary to AMD. METHODS: Eleven patients with treatment-naive "quiescent" CNV
      that consecutively presented over a 6-month period, underwent multimodal
      morphological and functional assessment (including indocyanine green angiography
      [ICGA], spectral-domain optical coherence tomography [SD-OCT], microperimetry,
      and preferential hyperacuity perimeter [PHP]). For the purpose of this study,
      asymptomatic previously untreated CNVs showing absence of intraretinal/subretinal
      exudation in two consecutive visits (at least 6 months apart) were defined as
      treatment-naive "quiescent" CNV. RESULTS: Eleven eyes of 11 patients (9 females;
      mean age 76.5 +/- 8.5 years) were included. On fluorescein angiography (FA),
      "quiescent" CNVs appeared as late speckled hyperfluorescent lesions lacking well
      demarcated borders. Mid-late phase ICGA allowed visualizing the hyperfluorescent
      "quiescent" CNV network and delineating the plaque. Mean lesion area (mid-late
      phase ICGA) appeared larger compared with earliest previous examination performed
      23.8 +/- 16.0 months before (3.24 +/- 2.51 mm(2) vs. 3.52 +/- 2.46 mm(2),
      respectively; P = 0.01). SD-OCT revealed, at the site of "quiescent" CNV, an
      irregularly slightly elevated RPE, without hyporeflective intraretinal/subretinal
      fluid, showing a major axis in the horizontal plane, which was characterized by
      collections of moderately reflective material in the sub-RPE space and clear
      visualization of the hyperreflective Bruch's membrane. Hypergeometric
      distribution revealed a significant correlation between microperimetry and PHP
      with respect to locations of "affected areas" (P = 0.001). CONCLUSIONS:
      "Quiescent" CNVs are sub-RPE CNVs secondary to AMD, showing absence of
      intraretinal/subretinal exudation on repeated OCT. "Quiescent" CNVs enlarge over
      time and may contribute to local reduced retinal sensitivity and metamorphopsia.

PMID- 24084096
TI  - Gene expression profile of cytokines and chemokines in skin lesions from
      Brazilian Indians with localized cutaneous leishmaniasis.
AB  - Cutaneous leishmaniasis (CL) is a chronic inflammatory disease caused by
      dermotropic Leishmania species belonging to the Viannia subgenera, with
      Leishmania (V.) braziliensis considered the main agent in Brazil. After
      infection, a local inflammatory process is initiated, inducing the expression of
      several cytokine/chemokine genes. We evaluated the immunity to CL of patients
      living in the indigenous community Xakriaba, Minas Gerais state, Brazil, by
      performing detailed analyses of the mRNA expression of different cytokines and
      chemokines in CL lesions, considering the time evolution (recent or late). We
      also studied the profile of the inflammatory infiltrate by histopathological
      analysis. The histopathological features of recent CL lesions showed an intense
      inflammatory reaction, characterized by the presence of both mononuclear and
      polymorphonuclear cells, whereas late CL lesions exhibited a predominance of
      mononuclear leukocytes. The gene expression of cytokines/chemokines in skin
      biopsies from the CL group showed higher transcript levels of modulatory (IL10
      and TGFB1), anti-inflammatory (IL4), and pro-inflammatory (TNF, IFNG, IL12B,
      CCL2, CCL3, CCL5, CXCL10) biomarkers in recent lesions than in late lesions. Our
      findings suggest that differential gene expression of cytokines and chemokines
      found in skin lesions from CL patients is associated with time evolution of
      lesions. 

PMID- 24084097
TI  - A novel nanoparticle containing MOG peptide with BTLA induces T cell tolerance
      and prevents multiple sclerosis.
AB  - Accumulative evidence demonstrates that multiple sclerosis (MS) is caused by
      activation of myelin Ag-reactive CD4+ T cells. Therefore, the CD4+ T cells
      specific for myelin Ag may be the important therapeutical target of MS. The novel
      coinhibitory receptor B and T lymphocyte attenuator (BTLA) may have a regulatory
      role in maintaining peripheral tolerance, however, its role in MS is still
      unknown. In this study, a novel nanoparticle containing MOG peptide with BTLA was
      designed and transduced into dendritic cells (DCs), and MOG peptide-induced EAE
      mice were administrated with the genetically modified DCs in vivo. The results
      demonstrated that modified DCs significantly enhanced the proportion of Foxp3+
      CD4+ regulatory T cells, increased IL-10 and TGF-beta cytokine secretion, while
      decreased IL-2 and IFN-gamma cytokine secretion. Furthermore, modified DCs
      supressed the CD4+ T cell response to MOG, cell infiltration into spinal cord,
      and the severity of EAE. In contrast, immune response to irrelevant exogenous Ag
      was not impaired by treatment with modified DCs. These findings suggested that
      DCs transduced with nanoparticle could induce specific CD4+ T-cells tolerance,
      which provided a promising therapeutic means to negatively manipulate immune
      response for autoimmune diseases without inhibition of the immune response to
      irrelevant Ag.

PMID- 24084098
TI  - Identification of amino acid residues involved in the interaction of canine IgE
      with canine and human FcepsilonRIalpha.
AB  - The interaction of immunoglobulin E (IgE) antibodies with the high-affinity
      receptor (FcepsilonRI) is important in anti-parasitic immunity and plays a
      central role in allergic responses. It has been shown that the human Cepsilon3
      domains comprise the binding sites for FcepsilonRIalpha and crystal structure
      determination has shown that amino acids in four sites contribute to the high
      affinity of the interaction. The role of homologous residues within canine IgE
      Fc, i.e. amino acids located at Cepsilon2-Cepsilon3 interface (residues 332-337),
      loop BC (residues 362-365), loop DE (residues 393-396), and loop FG (residues 424
      427) in canine Cepsilon3 domain were targeted by site-specific mutagenesis. The
      functional consequences of the mutations to support (i) IgE-mediated, antigen
      induced release of beta-hexosaminidase from RBL cells transfected with canine or
      human FcepsilonRIalpha and (ii) the affinity of the mutants for the soluble
      extracellular domain of the alpha-chain expressed in Pichia pastoris were
      determined by Surface Plasmon Resonance (SPR). Kinetic analysis supports the
      observed effects of IgE mutations on stimulus secretion coupling. Potential
      applications of this study, leading to the generation of an IgE variant with a
      disabled FcepsilonRIalpha binding site, are discussed.

PMID- 24084099
TI  - BAFF maintains T-cell survival by inducing OPN expression in B cells.
AB  - Dysregulation of T-cell survival and apoptosis is the common cause of autoimmune
      diseases such as multiple sclerosis (MS). However, the factors inducing imbalance
      of T-cell survival and apoptosis in MS remains unclear. Here, we show that the
      resistance to apoptosis was associated with high levels of B-cell activating
      factor (BAFF). Blockade of BAFF with TACI (transmembrane activator and calcium
      modulator and cyclophilin ligand interactor)-IgG significantly reduced T-cell
      survival in myelin oligodendroglia glycoprotein (MOG)-induced chronic
      experimental allergic encephalitis (EAE). Furthermore, BAFF induced anti
      apoptotic molecule Bcl2 expression in T cells by up-regulating osteopontin (OPN)
      secretion from B cells. BAFF mainly induced OPN expression in splenic CD21(
      )CD23(+) B cells via a NF-kB dependent signaling pathway. In addition, we found
      that BAFF and OPN levels were increased in MS patients similar to the results
      obtained from our mice research. The study suggests that BAFF regulates T-cell
      survival by inducing OPN secretion in B cells in autoimmune diseases.

PMID- 24084100
TI  - Potentiated macrophage activation by acid sensing under low adiponectin levels.
AB  - Adiponectin can protect against inflammation; one of the mechanisms involves
      direct, inhibition of macrophages (MPhi). We postulated that adiponectin anti
      sense transgenic (AsTg) mice raised in our laboratory are prone to inflammation
      because of systemic low adiponectin levels. The writhing response to acetic acid
      was utilized as an in vivo inflammatory model, and using Ca(2)(+), response to
      the acid was exploited in vitro to evaluate the function of resident peritoneal
      MPhi. The in vivo response to the acid was increased and the Ca(2)(+) response of
      MPhi was enhanced in AsTg mice, compared with those in wild type (WT) mice. In
      parallel with these enhanced responses, MPhi from AsTg mice augmented TNF-alpha
      and IL-6 mRNA expression. We further analyzed the enhancement in activity of MPhi
      from AsTg mice by acid sensing using specific inhibitors, amiloride for acid
      sensing ion channels (ASICs) and KB-R7943 for Na(+)/Ca(2)(+) exchangers (NCXs).
      Our results indicated that in AsTg mice, the Ca(2)(+) response to the acid was
      facilitated in MPhi by a low threshold of ASIC1 and NCX1 molecules and the
      activity of these channel was possibly regulated by adiponectin.

PMID- 24084101
TI  - A new approach to estimation of methane emission rates from landfills.
AB  - Methane emission monitoring has become increasingly essential for diffusive area
      sources, especially for landfills, which contribute to a significant fraction of
      the total anthropogenic methane emission globally. Statutorily, methane emission
      rate from landfills in Germany shall be examined on a semiannual basis; however,
      an appropriate approach has yet to be developed and adopted for general use. In
      this study, a new method is proposed based on experimental results, which
      utilizes a TDLAS (Tunable Diode Laser Absorption Spectroscopy) instrument -
      GasFinder2.0 system and a dispersion model LASAT (Lagrangian Simulation of
      Aerosol Transport) as the measurement device and calculation model, respectively.
      Between April 2010 and December 2011, a research project was conducted at a pilot
      scale landfill in the south of Germany. Drawing on the extensive research into
      this pilot project, an effective strategy of measurement setup was determined.
      Methane concentration was measured with GasFinder2.0 system in the upstream and
      downstream sections of the project site, while wind and turbulence data were
      measured simultaneously by an ultrasonic anemometer. The average methane emission
      rate from the source can be calculated by using the results as input data in the
      dispersion model. With this method, site-specific measurement approaches can be
      designed for not only landfills, but also different diffusive area sources with
      less workload and lower cost compared to conventional FID (Flame Ionization
      Detector) method.

PMID- 24084102
TI  - Floatability of polymer materials modulated by frothers.
AB  - Flotation tests of 35 polymer materials were carried out to investigate their
      floatability modulated by frothers. Results of flotation tests demonstrated that
      polymer resins and soft PVC showed high floatability, floatability of hard PVC
      plastics was relatively low and was related to the frothers, and there exists
      significant difference in the floatability of different post-consumer plastics.
      Flotation rate of post-consumer plastics varies from 0% to 100%. Furthermore,
      three-category low-energy surface (LES) was defined based on the hydrophile index
      of the materials involved in this paper, and an adsorption model was proposed to
      explain the results of flotation and to discuss the floatability of polymer
      materials modulated by frothers. Frother molecules are prone to adsorb on the
      surface of bubble rather than LES at relatively low concentration, bubble
      adsorbed by frother molecules is prone to approach first-category LES rather than
      third-category LES, and the structure of liquid film is formed on the first
      category LES at large concentration. Floatability of polymer materials modulated
      by frothers is further discussed: frothers increase the floatability of the first
      category LES but decrease the floatability of the third-category LES, while the
      floatability of the second-category LES is related to the type of frothers. 

PMID- 24084103
TI  - Sugarcane vinasse: environmental implications of its use.
AB  - The inadequate and indiscriminate disposal of sugarcane vinasse in soils and
      water bodies has received much attention since decades ago, due to environmental
      problems associated to this practice. Vinasse is the final by-product of the
      biomass distillation, mainly for the production of ethanol, from sugar crops
      (beet and sugarcane), starch crops (corn, wheat, rice, and cassava), or
      cellulosic material (harvesting crop residues, sugarcane bagasse, and wood).
      Because of the large quantities of vinasse produced, alternative treatments and
      uses have been developed, such as recycling of vinasse in fermentation,
      fertirrigation, concentration by evaporation, and yeast and energy production.
      This review was aimed at examining the available data on the subject as a
      contribution to update the information on sugarcane vinasse, from its
      characteristics and chemical composition to alternatives uses in Brazil:
      fertirrigation, concentration by evaporation, energy production; the effects on
      soil physical, chemical and biological properties; its influence on seed
      germination, its use as biostimulant and environmental contaminant. The low pH,
      electric conductivity, and chemical elements present in sugarcane vinasse may
      cause changes in the chemical and physical-chemical properties of soils, rivers,
      and lakes with frequent discharges over a long period of time, and also have
      adverse effects on agricultural soils and biota in general. Thus, new studies and
      green methods need to be developed aiming at sugarcane vinasse recycling and
      disposal. 

PMID- 24084104
TI  - Characterizing food waste substrates for co-digestion through biochemical methane
      potential (BMP) experiments.
AB  - Co-digestion of food waste with dairy manure is increasingly utilized to increase
      energy production and make anaerobic digestion more affordable; however, there is
      a lack of information on appropriate co-digestion substrates. In this study,
      biochemical methane potential (BMP) tests were conducted to determine the
      suitability of four food waste substrates (meatball, chicken, cranberry and ice
      cream processing wastes) for co-digestion with flushed dairy manure at a ratio of
      3.2% food waste and 96.8% manure (by volume), which equated to 14.7% (ice-cream)
      to 80.7% (chicken) of the VS being attributed to the food waste. All treatments
      led to increases in methane production, ranging from a 67.0% increase (ice cream
      waste) to a 2940% increase (chicken processing waste) compared to digesting
      manure alone, demonstrating the large potential methane production of food waste
      additions compared to relatively low methane production potential of the flushed
      dairy manure, even if the overall quantity of food waste added was minimal. 

PMID- 24084105
TI  - Pediatric primary care provider practices, knowledge, and attitudes of human
      immunodeficiency virus screening among adolescents.
AB  - OBJECTIVES: To evaluate pediatric primary care provider (PCP) HIV screening
      practices, knowledge, and attitudes. STUDY DESIGN: Anonymous cross-sectional,
      internet-based survey of pediatric PCPs from 29 primary care practices. Survey
      items assessed current HIV screening practices and knowledge, attitudes, and
      perceived barriers towards screening. Provider demographics and practice
      characteristics were analyzed for associations with screening through logistic
      regression. RESULTS: Of 190 PCPs, there were 101 evaluable responses (response
      rate: 53.2%). PCPs reported a screening rate for HIV of 39.6% ("most" or "all of
      the time") during routine adolescent visits compared with violence (60.4%),
      substance abuse (92.1%), and depression (94.1%) (P < .001). Less than 10% of PCPs
      correctly answered questions related to Centers for Disease Control and
      Prevention and state HIV screening recommendations. Of 20 potential HIV screening
      barriers assessed, mean number of reported barriers was 4.8 (SD +/- 2.9); with
      most concerns related to confidentiality, time for counseling, and follow-up. In
      a multivariable model, the only factor significantly associated with HIV
      screening "most" or "all of the time" during routine adolescent visits was urban
      practice site (aOR 9.8, 95% CI 2.9, 32.9). Provider type, sex, years since
      training, HIV screening guideline knowledge, and endorsing <=5 barriers were not
      associated with HIV screening. CONCLUSIONS: Although providers practicing in
      urban areas were more likely to report screening adolescents for HIV than those
      in suburban areas, overall self-reported screening rates were low, and several
      barriers were identified commonly. Future interventions should target increasing
      providers' knowledge and addressing concerns about confidentiality, requirements
      and counseling time, and follow-up of results.

PMID- 24084106
TI  - Infectious precipitants of acute hyperammonemia are associated with indicators of
      increased morbidity in patients with urea cycle disorders.
AB  - OBJECTIVE: To prospectively characterize acute hyperammonemic episodes in
      patients with urea cycle disorders (UCDs) in terms of precipitating factors,
      treatments, and use of medical resources. STUDY DESIGN: This was a prospective,
      longitudinal observational study of hyperammonemic episodes in patients with UCD
      enrolled in the National Institutes of Health-sponsored Urea Cycle Disorders
      Consortium Longitudinal Study. An acute hyperammonemic event was defined as
      plasma ammonia level >100 MUmol/L. Physician-reported data regarding the
      precipitating event and laboratory and clinical variables were recorded in a
      central database. RESULTS: In our study population, 128 patients with UCD
      experienced a total of 413 hyperammonemia events. Most patients experienced
      between 1 and 3 (65%) or between 4 and 6 (23%) hyperammonemia events since study
      inception, averaging fewer than 1 event/year. The most common identifiable
      precipitant was infection (33%), 24% of which were upper/lower respiratory tract
      infections. Indicators of increased morbidity were seen with infection, including
      increased hospitalization rates (P = .02), longer hospital stays (+2.0 days; P =
      .003), and increased use of intravenous ammonia scavengers (+45%-52%; P = .003
      .03). CONCLUSION: Infection is the most common precipitant of acute
      hyperammonemia in patients with UCD and is associated with indicators of
      increased morbidity (ie, hospitalization rate, length of stay, and use of
      intravenous ammonia scavengers). These findings suggest that the catabolic and
      immune effects of infection may be a target for clinical intervention in inborn
      errors of metabolism.

PMID- 24084107
TI  - Active angular alignment of gauge blocks in double-ended interferometers.
AB  - This paper presents a method implemented in a system for automatic contactless
      calibration of gauge blocks designed at ISI ASCR. The system combines low
      coherence interferometry and laser interferometry, where the first identifies the
      gauge block sides position and the second one measures the gauge block length
      itself. A crucial part of the system is the algorithm for gauge block alignment
      to the measuring beam which is able to compensate the gauge block lateral and
      longitudinal tilt up to 0.141 mrad. The algorithm is also important for the gauge
      block position monitoring during its length measurement. 

PMID- 24084108
TI  - Exploratory data analysis of acceleration signals to select light-weight and
      accurate features for real-time activity recognition on smartphones.
AB  - Smartphone-based activity recognition (SP-AR) recognizes users' activities using
      the embedded accelerometer sensor. Only a small number of previous works can be
      classified as online systems, i.e., the whole process (pre-processing, feature
      extraction, and classification) is performed on the device. Most of these online
      systems use either a high sampling rate (SR) or long data-window (DW) to achieve
      high accuracy, resulting in short battery life or delayed system response,
      respectively. This paper introduces a real-time/online SP-AR system that solves
      this problem. Exploratory data analysis was performed on acceleration signals of
      6 activities, collected from 30 subjects, to show that these signals are
      generated by an autoregressive (AR) process, and an accurate AR-model in this
      case can be built using a low SR (20 Hz) and a small DW (3 s). The high within
      class variance resulting from placing the phone at different positions was
      reduced using kernel discriminant analysis to achieve position-independent
      recognition. Neural networks were used as classifiers. Unlike previous works,
      true subject-independent evaluation was performed, where 10 new subjects
      evaluated the system at their homes for 1 week. The results show that our
      features outperformed three commonly used features by 40% in terms of accuracy
      for the given SR and DW. 

PMID- 24084109
TI  - Programmable gain amplifiers with DC suppression and low output offset for
      bioelectric sensors.
AB  - DC-offset and DC-suppression are key parameters in bioelectric amplifiers.
      However, specific DC analyses are not often explained. Several factors influence
      the DC-budget: the programmable gain, the programmable cut-off frequencies for
      high pass filtering and, the low cut-off values and the capacitor blocking issues
      involved. A new intermediate stage is proposed to address the DC problem
      entirely. Two implementations were tested. The stage is composed of a
      programmable gain amplifier (PGA) with DC-rejection and low output offset. Cut
      off frequencies are selectable and values from 0.016 to 31.83 Hz were tested, and
      the capacitor deblocking is embedded in the design. Hence, this PGA delivers most
      of the required gain with constant low output offset, notwithstanding the gain or
      cut-off frequency selected. 

PMID- 24084110
TI  - Taking advantage of selective change driven processing for 3D scanning.
AB  - This article deals with the application of the principles of SCD (Selective
      Change Driven) vision to 3D laser scanning. Two experimental sets have been
      implemented: one with a classical CMOS (Complementary Metal-Oxide Semiconductor)
      sensor, and the other one with a recently developed CMOS SCD sensor for
      comparative purposes, both using the technique known as Active Triangulation. An
      SCD sensor only delivers the pixels that have changed most, ordered by the
      magnitude of their change since their last readout. The 3D scanning method is
      based on the systematic search through the entire image to detect pixels that
      exceed a certain threshold, showing the SCD approach to be ideal for this
      application. Several experiments for both capturing strategies have been
      performed to try to find the limitations in high speed acquisition/processing.
      The classical approach is limited by the sequential array acquisition, as
      predicted by the Nyquist-Shannon sampling theorem, and this has been
      experimentally demonstrated in the case of a rotating helix. These limitations
      are overcome by the SCD 3D scanning prototype achieving a significantly higher
      performance. The aim of this article is to compare both capturing strategies in
      terms of performance in the time and frequency domains, so they share all the
      static characteristics including resolution, 3D scanning method, etc., thus
      yielding the same 3D reconstruction in static scenes.

PMID- 24084111
TI  - Identification and quantification of explosives in nanolitre solution volumes by
      Raman spectroscopy in suspended core optical fibers.
AB  - A novel approach for identifying explosive species is reported, using Raman
      spectroscopy in suspended core optical fibers. Numerical simulations are
      presented that predict the strength of the observed signal as a function of fiber
      geometry, with the calculated trends verified experimentally and used to optimize
      the sensors. This technique is used to identify hydrogen peroxide in water
      solutions at volumes less than 60 nL and to quantify microgram amounts of
      material using the solvent's Raman signature as an internal calibration standard.
      The same system, without further modifications, is also used to detect 1,4
      dinitrobenzene, a model molecule for nitrobenzene-based explosives such as 2,4,6
      trinitrotoluene (TNT). 

PMID- 24084112
TI  - A micro-force sensor with slotted-quad-beam structure for measuring the friction
      in MEMS bearings.
AB  - Presented here is a slotted-quad-beam structure sensor for the measurement of
      friction in micro bearings. Stress concentration slots are incorporated into a
      conventional quad-beam structure to improve the sensitivity of force
      measurements. The performance comparison between the quad-beam structure sensor
      and the slotted-quad-beam structure sensor are performed by theoretical modeling
      and finite element (FE) analysis. A hollow stainless steel probe is attached to
      the mesa of the sensor chip by a tailor-made organic glass fixture. Concerning
      the overload protection of the fragile beams, a glass wafer is bonded onto the
      bottom of sensor chip to limit the displacement of the mesa. The calibration of
      the packaged device is experimentally performed by a tri-dimensional positioning
      stage, a precision piezoelectric ceramic and an electronic analytical balance,
      which indicates its favorable sensitivity and overload protection. To verify the
      potential of the proposed sensor being applied in micro friction measurement, a
      measurement platform is established. The output of the sensor reflects the
      friction of bearing resulting from dry friction and solid lubrication. The
      results accord with the theoretical modeling and demonstrate that the sensor has
      the potential application in measuring the micro friction force under stable
      stage in MEMS machines. 

PMID- 24084114
TI  - A wireless laser displacement sensor node for structural health monitoring.
AB  - This study describes a wireless laser displacement sensor node that measures
      displacement as a representative damage index for structural health monitoring
      (SHM). The proposed measurement system consists of a laser displacement sensor
      (LDS) and a customized wireless sensor node. Wireless communication is enabled by
      a sensor node that consists of a sensor module, a code division multiple access
      (CDMA) communication module, a processor, and a power module. An LDS with a long
      measurement distance is chosen to increase field applicability. For a wireless
      sensor node driven by a battery, we use a power control module with a low-power
      processor, which facilitates switching between the sleep and active modes, thus
      maximizing the power consumption efficiency during non-measurement and non
      transfer periods. The CDMA mode is also used to overcome the limitation of
      communication distance, which is a challenge for wireless sensor networks and
      wireless communication. To evaluate the reliability and field applicability of
      the proposed wireless displacement measurement system, the system is tested
      onsite to obtain the required vertical displacement measurements during the
      construction of mega-trusses and an edge truss, which are the primary structural
      members in a large-scale irregular building currently under construction. The
      measurement values confirm the validity of the proposed wireless displacement
      measurement system and its potential for use in safety evaluations of structural
      elements. 

PMID- 24084113
TI  - N-acyl homoserine lactone-producing Pseudomonas putida strain T2-2 from human
      tongue surface.
AB  - Bacterial cell-to-cell communication (quorum sensing) refers to the regulation of
      bacterial gene expression in response to changes in microbial population density.
      Quorum sensing bacteria produce, release and respond to chemical signal molecules
      called autoinducers. Bacteria use two types of autoinducers, namely autoinducer-1
      (AI-1) and autoinducer-2 (AI-2) where the former are N-acylhomoserine lactones
      and the latter is a product of the luxS gene. Most of the reported literatures
      show that the majority of oral bacteria use AI-2 for quorum sensing but rarely
      the AI-1 system. Here we report the isolation of Pseudomonas putida strain T2-2
      from the oral cavity. Using high resolution mass spectrometry, it is shown that
      this isolate produced N-octanoylhomoserine lactone (C8-HSL) and N
      dodecanoylhomoserine lactone (C12-HSL) molecules. This is the first report of the
      finding of quorum sensing of P. putida strain T2-2 isolated from the human tongue
      surface and their quorum sensing molecules were identified. 

PMID- 24084115
TI  - Short chain N-acyl homoserine lactone production by soil isolate Burkholderia sp.
      strain A9.
AB  - In the bacteria kingdom, quorum sensing (QS) is a cell-to-cell communication that
      relies on the production of and response to specific signaling molecules. In
      proteobacteria, N-acylhomoserine lactones (AHLs) are the well-studied signaling
      molecules. The present study aimed to characterize the production of AHL of a
      bacterial strain A9 isolated from a Malaysian tropical soil. Strain A9 was
      identified as Burkholderia sp. using matrix-assisted laser desorption ionization
      time-of-flight mass spectrometry and 16S rDNA nucleotide sequence analysis. AHL
      production by A9 was detected with two biosensors, namely Chromobacterium
      violaceum CV026 and Escherichia coli [pSB401]. Thin layer chromatography results
      showed N-hexanoylhomoserine lactone (C6-HSL) and N-octanoylhomoserine lactone (C8
      HSL) production. Unequivocal identification of C6-HSL and C8-HSL was achieved by
      high resolution triple quadrupole liquid chromatography-mass spectrometry
      analysis. We have demonstrated that Burkholderia sp. strain A9 produces AHLs that
      are known to be produced by other Burkholderia spp. with CepI/CepR homologs. 

PMID- 24084116
TI  - Design and implementation of a MAC protocol for timely and reliable delivery of
      command and data in dynamic wireless sensor networks.
AB  - This paper proposes and implements a new TDMA-based MAC protocol for providing
      timely and reliable delivery of data and command for monitoring and control
      networks. In this kind of network, sensor nodes are required to sense data from
      the monitoring environment periodically and then send the data to a sink. The
      sink determines whether the environment is safe or not by analyzing the acquired
      data. Sometimes, a command or control message is sent from the sink to a
      particular node or a group of nodes to execute the services or request further
      interested data. The proposed MAC protocol enables bidirectional communication,
      controls active and sleep modes of a sensor node to conserve energy, and
      addresses the problem of load unbalancing between the nodes near a sink and the
      other nodes. It can improve reliability of communication significantly while
      extending network lifetime. These claims are supported by the experimental
      results. 

PMID- 24084117
TI  - A new corrosion sensor to determine the start and development of embedded rebar
      corrosion process at coastal concrete.
AB  - The corrosion of reinforcements induced by chloride has resulted to be one of the
      most frequent causes of their premature damage. Most corrosion sensors were
      designed to monitor corrosion state in concrete, such as Anode-Ladder-System and
      Corrowatch System, which are widely used to monitor chloride ingress in marine
      concrete. However, the monitoring principle of these corrosion sensors is based
      on the macro-cell test method, so erroneous information may be obtained,
      especially from concrete under drying or saturated conditions due to concrete
      resistance taking control in macro-cell corrosion. In this paper, a fast weak
      polarization method to test corrosion state of reinforcements based on
      electrochemical polarization dynamics was proposed. Furthermore, a new corrosion
      sensor for monitoring the corrosion state of concrete cover was developed based
      on the proposed test method. The sensor was tested in cement mortar, with dry-wet
      cycle tests to accelerate the chloride ingress rate. The results show that the
      corrosion sensor can effectively monitor chloride penetration into concrete with
      little influence of the relative humidity in the concrete. With a reasonable
      corrosion sensor electrode arrangement, it seems the Ohm-drop effect measured by
      EIS can be ignored, which makes the tested electrochemical parameters more
      accurate. 

PMID- 24084118
TI  - Quantification of mesenchymal stem cell growth rates through secretory and
      excretory biomolecules in conditioned media via Fresnel reflection.
AB  - An efficient and low cost optical method for directly measuring the concentration
      of homogenous biological solutes is proposed and demonstrated. The proposed
      system operates by Fresnel reflection, with a flat-cleaved single-mode fiber
      serving as the sensor probe. A laser provides a 12.9 dBm sensor signal at 1,550
      nm, while a computer-controlled optical power meter measures the power of the
      signal returned by the probe. Three different mesenchymal stem cell (MSC) lines
      were obtained, sub-cultured and trypsinized daily over 9 days. Counts were
      measured using a haemocytometer and the conditioned media (CM) was collected
      daily and stored at -80  degrees C. MSCs release excretory biomolecules
      proportional to their growth rate into the CM, which changes the refractive index
      of the latter. The sensor is capable of detecting changes in the number of stem
      cells via correlation to the change in the refractive index of the CM, with the
      measured power loss decreasing approximately 0.4 dB in the CM sample per average
      1,000 cells in the MSC subculture. The proposed system is highly cost-effective,
      simple to deploy, operate, and maintain, is non-destructive, and allows reliable
      real-time measurement of various stem cell proliferation parameters. 

PMID- 24084119
TI  - Hyperspectral reflectance imaging technique for visualization of moisture
      distribution in cooked chicken breast.
AB  - Spectroscopy has proven to be an efficient tool for measuring the properties of
      meat. In this article, hyperspectral imaging (HSI) techniques are used to
      determine the moisture content in cooked chicken breast over the VIS/NIR (400
      1,000 nm) spectral range. Moisture measurements were performed using an oven
      drying method. A partial least squares regression (PLSR) model was developed to
      extract a relationship between the HSI spectra and the moisture content. In the
      full wavelength range, the PLSR model possessed a maximum  of 0.90 and an SEP of
      0.74%. For the NIR range, the PLSR model yielded an  of 0.94 and an SEP of 0.71%.
      The majority of the absorption peaks occurred around 760 and 970 nm, representing
      the water content in the samples. Finally, PLSR images were constructed to
      visualize the dehydration and water distribution within different sample regions.
      The high correlation coefficient and low prediction error from the PLSR analysis
      validates that HSI is an effective tool for visualizing the chemical properties
      of meat. 

PMID- 24084120
TI  - Application of a coaxial-like sensor for impedance spectroscopy measurements of
      selected low-conductivity liquids.
AB  - The paper presents a coaxial-like sensor operating in the 20 Hz-2 MHz frequency
      range used to determine the electrical properties of selected liquids of low
      electrical conductivity. Examined materials included low-concentrated aqueous
      solutions of potassium chloride, sodium chloride and trisodium citrate, which are
      common food additives. Impedance spectra of the measurement cell filled with
      particular liquids were obtained and analyzed using the electrical equivalent
      circuit approach. The values of physical quantities and parameters describing the
      equivalent circuit components, including a constant phase element, were
      calculated for each sample. The applied sensor was also calibrated for electrical
      conductivity measurements up to 8 mS/m. The constant phase element parameters
      differed among the studied solutions and concentrations. This may provide a basis
      for a detection method of small amounts of compounds, such as food additives in
      low-concentrated aqueous solutions. To demonstrate the potential of the presented
      method, samples of purchased mineral water and a flavored drink containing
      various additives were tested. 

PMID- 24084121
TI  - A visual servoing-based method for ProCam systems calibration.
AB  - Projector-camera systems are currently used in a wide field of applications, such
      as 3D reconstruction and augmented reality, and can provide accurate
      measurements, depending on the configuration and calibration. Frequently, the
      calibration task is divided into two steps: camera calibration followed by
      projector calibration. The latter still poses certain problems that are not easy
      to solve, such as the difficulty in obtaining a set of 2D-3D points to compute
      the projection matrix between the projector and the world. Existing methods are
      either not sufficiently accurate or not flexible. We propose an easy and
      automatic method to calibrate such systems that consists in projecting a
      calibration pattern and superimposing it automatically on a known printed
      pattern. The projected pattern is provided by a virtual camera observing a
      virtual pattern in an OpenGL model. The projector displays what the virtual
      camera visualizes. Thus, the projected pattern can be controlled and superimposed
      on the printed one with the aid of visual servoing. Our experimental results
      compare favorably with those of other methods considering both usability and
      accuracy. 

PMID- 24084122
TI  - Lower limb wearable capacitive sensing and its applications to recognizing human
      gaits.
AB  - In this paper, we present an approach to sense human body capacitance and apply
      it to recognize lower limb locomotion modes. The proposed wearable sensing system
      includes sensing bands, a signal processing circuit and a gait event detection
      module. Experiments on long-term working stability, adaptability to disturbance
      and locomotion mode recognition are carried out to validate the effectiveness of
      the proposed approach. Twelve able-bodied subjects are recruited, and eleven
      normal gait modes are investigated. With an event-dependent linear discriminant
      analysis classifier and feature selection procedure, four time-domain features
      are used for pattern recognition and satisfactory recognition accuracies (97:3%
      +/- 0:5%, 97:0% +/- 0:4%, 95:6% +/- 0:9% and 97:0% +/- 0:4% for four phases of
      one gait cycle respectively) are obtained. The accuracies are comparable with
      that from electromyography-based systems and inertial-based systems. The results
      validate the effectiveness of the proposed lower limb capacitive sensing approach
      in recognizing human normal gaits. 

PMID- 24084123
TI  - Digital sequences and a time reversal-based impact region imaging and
      localization method.
AB  - To reduce time and cost of damage inspection, on-line impact monitoring of
      aircraft composite structures is needed. A digital monitor based on an array of
      piezoelectric transducers (PZTs) is developed to record the impact region of
      impacts on-line. It is small in size, lightweight and has low power consumption,
      but there are two problems with the impact alarm region localization method of
      the digital monitor at the current stage. The first one is that the accuracy rate
      of the impact alarm region localization is low, especially on complex composite
      structures. The second problem is that the area of impact alarm region is large
      when a large scale structure is monitored and the number of PZTs is limited which
      increases the time and cost of damage inspections. To solve the two problems, an
      impact alarm region imaging and localization method based on digital sequences
      and time reversal is proposed. In this method, the frequency band of impact
      response signals is estimated based on the digital sequences first. Then,
      characteristic signals of impact response signals are constructed by sinusoidal
      modulation signals. Finally, the phase synthesis time reversal impact imaging
      method is adopted to obtain the impact region image. Depending on the image, an
      error ellipse is generated to give out the final impact alarm region. A
      validation experiment is implemented on a complex composite wing box of a real
      aircraft. The validation results show that the accuracy rate of impact alarm
      region localization is approximately 100%. The area of impact alarm region can be
      reduced and the number of PZTs needed to cover the same impact monitoring region
      is reduced by more than a half. 

PMID- 24084124
TI  - An OP4 functional stream in the language-related neuroarchitecture.
AB  - Sensory comprehension and motor production of language symbols form the basis of
      human speech. Classical neuroanatomy has pointed to Wernicke's and Broca's areas
      as playing important roles in the integration of these 2 functions. However,
      recent studies have proposed that more direct pathways may exist between auditory
      input and motor output, bypassing Wernicke's and Broca's areas. We used
      functional network analyses to investigate potential auditory-motor (A-M)
      couplings between language-related cortices. We found that operculum parietale
      (OP) interconnectivity in region OP4 seems to play a critical role in the A-M
      integration of the brain. This finding supports a novel landscape in the
      functional neuroarchitecture that sustains language in humans. 

PMID- 24084125
TI  - The zinc finger transcription factor RP58 negatively regulates Rnd2 for the
      control of neuronal migration during cerebral cortical development.
AB  - The zinc finger transcription factor RP58 (also known as ZNF238) regulates
      neurogenesis of the mouse neocortex and cerebellum (Okado et al. 2009; Xiang et
      al. 2011; Baubet et al. 2012; Ohtaka-Maruyama et al. 2013), but its mechanism of
      action remains unclear. In this study, we report a cell-autonomous function for
      RP58 during the differentiation of embryonic cortical projection neurons via its
      activities as a transcriptional repressor. Disruption of RP58 expression alters
      the differentiation of immature neurons and impairs their migration and
      positioning within the mouse cerebral cortex. Loss of RP58 within the embryonic
      cortex also leads to elevated mRNA for Rnd2, a member of the Rnd family of
      atypical RhoA-like GTPase proteins important for cortical neuron migration (Heng
      et al. 2008). Mechanistically, RP58 represses transcription of Rnd2 via binding
      to a 3'-regulatory enhancer in a sequence-specific fashion. Using reporter
      assays, we found that RP58 repression of Rnd2 is competed by proneural basic
      helix-loop-helix transcriptional activators. Finally, our rescue experiments
      revealed that negative regulation of Rnd2 by RP58 was important for cortical cell
      migration in vivo. Taken together, these studies demonstrate that RP58 is a key
      player in the transcriptional control of cell migration in the developing
      cerebral cortex. 

PMID- 24084126
TI  - Perturbing the action observation network during perception and categorization of
      actions' goals and grips: state-dependency and virtual lesion TMS effects.
AB  - Watching others grasping and using objects activates an action observation
      network (AON), including inferior frontal (IFC), anterior intraparietal (AIP),
      and somatosensory cortices (S1). Yet, causal evidence of the differential
      involvement of such AON sensorimotor nodes in representing high- and low-level
      action components (i.e., end-goals and grip type) is meager. To address this
      issue, we used transcranial magnetic stimulation-adaptation (TMS-A) during 2
      novel action perception tasks. Participants were shown adapting movies displaying
      a demonstrator performing goal-directed actions with a tool, using either power
      or precision grips. They were then asked to match the end-goal (Goal-recognition
      task) or the grip (Grip-recognition task) of actions shown in test pictures to
      the adapting movies. TMS was administered over IFC, AIP, or S1 during
      presentation of test pictures. Virtual lesion-like effects were found in the Grip
      recognition task where IFC stimulation induced a general performance decrease,
      suggesting a critical role of IFC in perceiving grips. In the Goal-recognition
      task, IFC and S1 stimulation differently affected the processing of "adapted" and
      "nonadapted" goals. These "state-dependent" effects suggest that the overall goal
      of seen actions is encoded into functionally distinct and spatially overlapping
      neural populations in IFC-S1 and such encoding is critical for recognizing and
      understanding end-goals. 

PMID- 24084127
TI  - Transcranial magnetic stimulation (TMS) of the supramarginal gyrus: a window to
      perception of upright.
AB  - Although the pull of gravity, primarily detected by the labyrinth, is the
      fundamental input for our sense of upright, vision and proprioception must also
      be integrated with vestibular information into a coherent perception of spatial
      orientation. Here, we used transcranial magnetic stimulation (TMS) to probe the
      role of the cortex at the temporal parietal junction (TPJ) of the right cerebral
      hemisphere in the perception of upright. We measured the perceived vertical
      orientation of a visual line; that is, the subjective visual vertical (SVV),
      after a short period of continuous theta burst stimulation (cTBS) with the head
      upright. cTBS over the posterior aspect of the supramarginal gyrus (SMGp) in 8
      right-handed subjects consistently tilted the perception of upright when tested
      with the head tilted 20 degrees  to either shoulder (right: 3.6 degrees , left:
      2.7 degrees ). The tilt of SVV was always in the direction opposite to the head
      tilt. On the other hand, there was no significant tilt after sham stimulation or
      after cTBS of nearby areas. These findings suggest that a small area of cerebral
      cortex--SMGp--has a role in processing information from different sensory
      modalities into an accurate perception of upright.

PMID- 24084128
TI  - Functional interactions between large-scale networks during memory search.
AB  - Neuroimaging studies have identified two major large-scale brain networks, the
      default mode network (DMN) and the dorsal attention network (DAN), which are
      engaged for internally and externally directed cognitive tasks respectively, and
      which show anticorrelated activity during cognitively demanding tests and at
      rest. We identified these brain networks using independent component analysis
      (ICA) of functional magnetic resonance imaging data, and examined their
      interactions during the free-recall task, a self-initiated memory search task in
      which retrieval is performed in the absence of external cues. Despite the
      internally directed nature of the task, the DAN showed transient engagement in
      the seconds leading up to successful retrieval. ICA revealed a fractionation of
      the DMN into 3 components. A posteromedial network increased engagement during
      memory search, while the two others showed suppressed activity during memory
      search. Cooperative interactions between this posteromedial network, a right
      lateralized frontoparietal control network, and a medial prefrontal network were
      maintained during memory search. The DAN demonstrated heterogeneous task
      dependent shifts in functional coupling with various subnetworks within the DMN.
      This functional reorganization suggests a broader role of the DAN in the absence
      of externally directed cognition, and highlights the contribution of the
      posteromedial network to episodic retrieval. 

PMID- 24084129
TI  - Opportunities abound, so make yourself available.

PMID- 24084130
TI  - Dietary fiber information for individuals with Crohn disease: reports of
      gastrointestinal effects.
AB  - The experiences of individuals with Crohn disease before and after receiving
      dietary fiber information have not been described in the literature. This article
      offers findings from a study that used four semistructured audiorecorded
      interviews during a 4-week time period for the purpose of exploring the
      experiences of 11 individuals before and after receiving dietary fiber
      information from a healthcare professional. The first and second interviews
      occurred immediately before and after the presentation of information. Follow-up
      interviews occurred at 2-week intervals. Thematic analysis of the baseline
      interviews revealed 2 themes: (a) accepting a redefined (lower expectations)
      definition of normal quality of life and (b) continuing to look for answers.
      Three themes emerged from the follow-up interviews at Week 4: (a) reevaluating
      old diet-related concepts, (b) enjoying a healthier lifestyle at a self-set pace,
      and (c) enjoying positive physical effects of wheat bran consumption. This
      article examines the 3rd postintervention theme, "enjoying physical effects of
      wheat bran consumption." The relevance of this research is that nurses equipped
      with dietary fiber information may be better able to help some individuals with
      Crohn disease to explore the potential benefits of a well-rounded nutritious
      pattern of eating that includes wheat bran cereal. 

PMID- 24084131
TI  - The incidence of upper extremity injuries in endoscopy nurses working in the
      United States.
AB  - Numerous studies have addressed musculoskeletal disorders in the international
      working population. The literature indicates that injuries exist at astounding
      rates with significant economic impact. Attempts have been made by government,
      private industry, and special interest groups to address the issues related to
      the occurrence and prevention of musculoskeletal injuries. Because of the limited
      research on the gastrointestinal (GI) endoscopy nursing sector, this descriptive,
      correlational study explored the incidence of upper extremity injuries in GI
      endoscopy nurses and technicians in the United States. A total of 215 subjects
      were included in the study. Findings show that upper extremity injuries exist
      among nurses working in GI endoscopy. Twenty-two percent of respondents missed
      work for upper extremity injuries. The findings also show that the severity of
      disability is related to the type of work done, type of assistive aids available
      at work, and whether or not ergonomic or physiotherapy assessments were provided
      at the place of employment. In reference to rate of injury and the availability
      of ergonomics and physiotherapy assessments, those who had ergonomic assessments
      available to them had scores on the Disabilities of the Arm, Shoulder, and Hand
      (DASH) inventory (indicating upper extremity disability) that were significantly
      lower (DASH score, 9.96) than those who did not have the assessments available
      (DASH score, 14.66). The results suggest that there are a significant number of
      subjects who are disabled to varying degrees and the majority of these are
      employed in full-time jobs. 

PMID- 24084132
TI  - How the gastroenterology nurse and provider can implement prescriptive exercise.
AB  - Exercise is Medicine is a global health initiative of the American College of
      Sports Medicine. Their goal is to improve the health of every patient through
      prescriptive exercise, which is a goal-oriented plan for any patient to increase
      physical exercise. The gastrointestinal nurse works in various settings with a
      variety of patients who have numerous chief complaints that can be helped by
      prescriptive exercise. Resources the patient, nurse, and provider can use to help
      patients reach their exercise goals are discussed. The amount of time required
      for these activities is minimal and can be accomplished by the gastrointestinal
      nurse and provider in 15-20 seconds during a normal office visit. 

PMID- 24084133
TI  - Quality of life, depression, and anxiety among hepatitis B patients.
AB  - This descriptive cross-sectional study was designed to determine the depression
      and anxiety levels, and their effects, on quality of life of patients with
      chronic Hepatitis B. Chronic infection with Hepatitis B virus has a profound
      effect on health-related quality of life. Medications, including interferon, that
      are commonly used to treat chronic viral Hepatitis B may cause depression as an
      adverse effect. However, little is known about the impact of depression and
      anxiety on quality of life in patients with Hepatitis B. A total of 96 patients
      aged between 15 and 61 years were included in the study. Slightly more than half
      of them (52%) were female. Three scales-the Beck Depression Inventory, Beck
      Anxiety Scale, and Short Form of the World Health Organization Quality of Life
      Questionnaire (WHOQOL-BREF)-were used in the study. The scores obtained from the
      BDS in 91.7% of the patients were above the cutoff value of 17. Moreover, 80
      patients received interferon. There was a negative correlation between the
      physical, environmental, and cultural areas on the Beck Anxiety Scale and WHOQOL
      BREF (Turkish) (p< .05). A high level of depressive symptoms was established in
      this study, and the physical, environmental, and cultural aspects of quality of
      life were determined to increase as the anxiety level increased. 

PMID- 24084134
TI  - Endoscopic management of ingested foreign bodies and food impactions.
AB  - Endoscopy plays a major role in the management of foreign bodies and food
      impactions. Because of their frequent occurrence and potential for complications,
      it is important for the gastroenterology nurse and associate to gain an
      understanding of the incidence, diagnosis, and management of patients who present
      with ingested foreign bodies or food impaction. This article summarizes the
      clinical approach to patient: assessment, preparation for endoscopic procedure,
      preparation of endoscopic accessories, and follow-up care. Finally, an
      interesting case presentation highlights key components of caring for patients
      requiring endoscopic intervention. 

PMID- 24084136
TI  - The ileus and oddities after colorectal surgery.
AB  - Colorectal surgery is a necessity for many disease processes such as
      diverticulitis, ulcerative colitis, Crohn disease, and colorectal cancers as well
      as for the many complications of such conditions. The incidence of overall
      complications related to colorectal surgery has been reported to be between 10%
      and 30%. Prevention is the necessary key to avoid complications and this may be
      improved by adequate selection of appropriate procedures for the patient, good
      surgical technique, and good postoperative care. Nevertheless, complications do
      occur intraoperatively or postoperatively and must be managed in a timely manner
      to improve overall patient outcomes. Such complications include paralytic ileus,
      anastomotic leak, abdominal sepsis, acute mesenteric ischemia, anastomotic
      bleeding and hemorrhage, wound infection, anastomotic dehiscence and fistula
      formation, small bowel obstruction, and genitourinary complications. 

PMID- 24084138
TI  - Nausea and vomiting: mechanisms and treatment overview.

PMID- 24084139
TI  - A young woman with adverse effects from an alternative treatment.

PMID- 24084140
TI  - Nonprescription product safety: education needed for consumers and healthcare
      professionals.

PMID- 24084141
TI  - Investigation of osteopontin levels and genomic variation of osteopontin and its
      receptors in Type 1 diabetes mellitus.
AB  - BACKGROUND: Failure in self-tolerance towards beta-cells in diabetes mellitus
      (DM) pathogenesis involves a series of complex events that are governed by
      environmental and genetic factors. Considering the importance of osteopontin
      (OPN) in T-helper-1 (Th1) cells development, the aim of this study was to
      evaluate the serum level and gene polymorphism of OPN in Iranian Type 1 diabetic
      (T1DM) children. METHODS: In this case-control study, 87 T1DM children and 86
      healthy ones were enrolled. Blood samples of both groups were checked for OPN
      level. The single nucleotide polymorphisms (SNP) were genotyped by RFLP analysis
      for OPN rs1126772, its receptor integrin alpha4 (ITGA4) rs 1449263, and CD44
      rs8193. RESULTS: Serum levels of OPN in diabetic children were significantly
      higher in cases compared to the control group (p=0.023), but there was no
      significant relationship between OPN rs1126772 (p=0.79), its receptor integrin
      alpha4 (p=0.31), and CD44 rs8193 (p=0.45), and T1DM. CONCLUSION: Higher amounts
      of OPN were seen in T1DM children. It is assumed that OPN might have inducing
      effects on T1DM development, particularly when genetically susceptible
      individuals are predisposed by an environmental insult. However, the 3 SNPs of
      OPN and its receptors did not show noticeable association with T1DM. The power of
      our study (~19%) was insufficient to observe any significant statistical
      difference between the groups; moreover, this study does not exclude the
      possibility of association of other SNPs of OPN and its receptors with this
      disease, and more studies are needed to clarify the issue.

PMID- 24084142
TI  - Physical activity, life events stress, cortisol, and DHEA: preliminary findings
      that physical activity may buffer against the negative effects of stress.
AB  - The present study examined the relationship between habitual physical activity,
      life events stress, the diurnal rhythms of cortisol and DHEA, and the
      cortisol:dehydroepiandrosterone (DHEA) ratio in older adults. Thirty-six
      participants aged >= 65 reported their habitual physical activity, and indicated
      if a particular event happened to them in the past year (stress incidence) and
      how stressful they perceived the event to be (stress severity). Older adults with
      higher stress severity demonstrated a significantly higher cortisol:DHEA ratio.
      Individuals with higher stress incidence scores and who did not participate in
      aerobic exercise had a significantly higher cortisol:DHEA ratio and flatter DHEA
      diurnal rhythm compared with those who regularly participated in aerobic
      exercise. In conclusion, life events stress may have a negative impact on the
      cortisol:DHEA ratio in older adults. Under conditions of high stress exposure,
      exercise may protect older adults from an increased cortisol:DHEA ratio and
      flatter DHEA diurnal rhythm. 

PMID- 24084143
TI  - Colchicine treatment in children with familial Mediterranean fever: is it a risk
      factor for neuromyopathy?
AB  - BACKGROUND: We cared for a 17-year-old adolescent with familial Mediterranean
      fever under colchicine treatment. Because of the increased creatinine kinase
      level (3937 U/L) observed in this individual, we planned to assess all pediatric
      patients with familial Mediterranean fever under colchicine treatment to detect
      any resultant neuromyopathy. METHODS: The study included 88 children with
      familial Mediterranean fever who were receiving colchicine. The patient with
      myopathy was not included in the study. Serum creatinine kinase levels were
      measured and nerve conduction studies were carried out in all patients. RESULTS:
      The study included 88 patients (47 female, 53.4%) with an average age of 10.1 +/-
      3.35 years. The average period of colchicine use was 28.25 +/- 17.66 months. Side
      effects of colchicine were detected in 10 patients (11%)--as diarrhea in eight
      patients, leukopenia in one patient, and hair loss in one patient. Nerve
      conduction studies determined incidental carpal tunnel syndrome in only one
      patient. CONCLUSIONS: Our study did not suggest an elevated risk of neuromyopathy
      associated with the use of colchicine for familial Mediterranean fever.

PMID- 24084144
TI  - Microcephaly thin corpus callosum intellectual disability syndrome caused by
      mutated TAF2.
AB  - BACKGROUND: The combination of microcephaly, pyramidal signs, abnormal corpus
      callosum, and intellectual disability presents a diagnostic challenge. We
      describe an autosomal recessive disorder characterized by microcephaly, pyramidal
      signs, thin corpus callosum, and intellectual disability. METHODS: We previously
      mapped the locus for this disorder to 8q23.2-q24.12; the candidate region
      included 22 genes. We performed Sanger sequencing of 10 candidate genes; to
      ensure other genes in the candidate region do not harbor mutations, we sequenced
      the exome of one affected individual. RESULTS: We identified two homozygous
      missense changes, p.Thr186Arg and p.Pro416His in TAF2, which encodes a
      multisubunit cofactor for TFIID-dependent RNA polymerase II-mediated
      transcription, in all affected individuals. CONCLUSIONS: We propose that the
      disorder is caused by the more conserved mutation p.Thr186Arg, with the second
      sequence change identified, p.Pro416His, possibly further negatively affecting
      the function of the protein. However, it is unclear which of the two changes, or
      maybe both, represents the causative mutation. A single missense mutation in TAF2
      in a family with microcephaly and intellectual disability was described in a
      large-scale study reporting on the identification of 50 novel genes. We suggest
      that a mutation in TAF2 can cause this syndrome.

PMID- 24084145
TI  - Piezoelectric surgery in maxillary sinus floor elevation with hydraulic pressure
      for xenograft and simultaneous implant placement.
AB  - Because of the low bone quality in the posterior maxilla, edentulism in this area
      often results in a resorbed osseous structure and a pneumatized maxillary sinus,
      which makes dental implant surgery in the posterior maxilla a challenge. Two main
      surgical approaches are available for the sinus lift procedure: lateral and
      crestal. Improvement of the maxillary sinus floor elevation technique and
      increase in predictability are desirable. This article describes an innovative
      approach to maxillary sinus floor elevation with piezoelectric surgery and
      hydraulic pressure for xenograft and simultaneous implant placement in situations
      with insufficient residual alveolar bone. 

PMID- 24084146
TI  - Effect of cavity design on tooth surface strain.
AB  - STATEMENT OF PROBLEM: The loss of tooth structure can increase cuspal flexure,
      thereby reducing the fracture resistance of the tooth, or open the tooth
      restoration interface, leading to microleakage. PURPOSE: The purpose of this
      study was to evaluate tooth strain in teeth with different cavity preparations
      after loading and unloading. MATERIAL AND METHODS: Ten intact human maxillary
      premolars were selected and embedded in epoxy resin molds. Constantan strain
      gauges were used and tested as an intact tooth (group I), occlusal cavity (group
      O), mesio-occlusal cavity (group MO), and finally mesio-occluso-distal cavity
      (group MOD). All teeth were subjected to gradual nondestructive occlusal loading
      and unloading (50 N, 70 N, 90 N, 110 N, 130 N, 50 N, 0 N) in a servohydraulic
      testing machine. All data were analyzed statistically by performing a repeated
      measures ANOVA with load and cavity as factors to compare the relevant mean
      strains, and a Bonferroni post hoc test was performed for multiple comparisons
      (alpha=.05). RESULTS: The repeated measures ANOVA did not provide any evidence of
      an interaction between load and cavity but indicated a significant difference in
      the mean strains both between the loads (P<.001) and between the cavity groups
      (P<.001). CONCLUSIONS: MOD cavities presented statistically significantly higher
      values of strain than MO, O, or intact teeth, and a significant increase in the
      values of mean strain for all cavities was observed, even with intact teeth, when
      nondestructive occlusal loading was increased.

PMID- 24084147
TI  - Coronary artery ectasia as a culprit for acute myocardial infarction: review of
      pathophysiology and management.
AB  - Coronary artery ectasia (CAE) is defined as localized coronary dilatation, which
      exceeds the diameter of normal adjacent segments or the diameter of the patient's
      largest coronary vessel by 1.5 times. The pathophysiology of CAE remains unclear
      as its relationship with atherosclerosis remains only modestly established. The
      histological variances and conflicting reports of the role of traditional
      cardiovascular risk factors, also, weakens the significance of such association.
      The slow coronary flow (CSF) of CAE may lead to ischemic and thrombotic events, a
      mechanism that has never been fully elucidated, but may play a fundamental role
      in its pathogenesis. While pure, non-atherosclerotic, CAE is believed to have
      better prognosis when compared to atherosclerotic obstructive CAE, it is thought
      that CAE is not a simple condition but rather has an adverse clinical course.
      Nevertheless, long-term prognosis and outcome of CAE is similar to
      atherosclerotic-non-CAE. Since CAE was first described, oral anticoagulants have
      been considered as a valid treatment option. Dual antiplatelet therapy is widely
      employed in acute coronary syndrome (ACS), which also applies to CAE patients
      presenting with ACS. However, there is a significant uncertainty about the best
      treatment strategy for CAE in acute myocardial infarction. We hereby report a
      variety of presentations of CAE complicated with ST elevation myocardial
      infarction (STEMI). Pathophysiological and anatomical varieties of ectatic
      coronary culprit lesions represent clinical challenges in uniformly managing this
      condition. Our review is unique in critically showing the pathophysiology,
      available controversial evidence upon management and prognostic features of CAE
      with STEMI. 

PMID- 24084148
TI  - Is there a role of MMA T wave alternans test for risk assessment in Brugada
      syndrome?

PMID- 24084149
TI  - Effects of radiofrequency ablation on levels of cardiac biochemical markers in
      patients with atrioventricular nodal re-entry tachycardia.

PMID- 24084150
TI  - Spontaneous closure of a type 3 coronary artery perforation after percutaneous
      coronary intervention.

PMID- 24084151
TI  - Ablation of heterogeneous zone eliminates ventricular tachycardia: Can cardiac MR
      be a criterion for successful ablation?

PMID- 24084152
TI  - Severe tricuspid regurgitation after blunt chest trauma due to chordal rupture: a
      rare complication.

PMID- 24084153
TI  - Almanac 2013: cardiac arrhythmias and pacing.
AB  - Important advances have been made in the past few years in the fields of clinical
      cardiac electrophysiology and pacing. Researchers and clinicians have a greater
      understanding of the pathophysiological mechanisms underlying atrial fibrillation
      (AF), which has transpired into improved methods of detection, risk
      stratification, and treatments. The introduction of novel oral anticoagulants has
      provided clinicians with alternative options in managing patients with AF at
      moderate to high thromboembolic risk and further data has been emerging on the
      use of catheter ablation for the treatment of symptomatic AF. Another area of
      intense research in the field of cardiac arrhythmias and pacing is in the use of
      cardiac resynchronisation therapy (CRT) for the treatment of patients with heart
      failure. Following the publication of major landmark randomised controlled trials
      reporting that CRT confers a survival advantage in patients with severe heart
      failure and improves symptoms, many subsequent studies have been performed to
      further refine the selection of patients for CRT and determine the clinical
      characteristics associated with a favourable response. The field of sudden
      cardiac death and implantable cardioverter defibrillators also continues to be
      actively researched, with important new epidemiological and clinical data
      emerging on improved methods for patient selection, risk stratification, and
      management. This review covers the major recent advances in these areas related
      to cardiac arrhythmias and pacing. 

PMID- 24084154
TI  - Gender specific association of ABCA1 gene R219K variant in coronary disease risk
      through interactions with serum triglyceride elevation in Turkish adults.
AB  - OBJECTIVE: ATP binding cassette transporter A1 (ABCA1) controls the reverse
      cholesterol transport. Some ABCA1 variants are correlated with serum high-density
      lipoprotein cholesterol (HDL-C) and other lipid concentrations. We aimed to
      explore the relationship of ABCA1 gene with both the lipid profile and coronary
      heart disease (CHD) risk. METHODS: Selected 627 individuals of the Turkish Adult
      Risk Factor Study were genotyped for ABCA1 R219K polymorphism using PCR-RFLP
      (polymerase chain reaction-restriction fragment length polymorphism) method.
      Student's t-test, one-way ANOVA, Chi-square test, linear and logistic regression
      was used for statistical analysis. RESULTS: We demonstrated a gender-specific
      effect of the R219K polymorphism on plasma lipids and CHD. In men, while
      homozygosity of the K allele was associated with increased plasma low-density
      lipoprotein cholesterol (LDL-C) (p<0.05) and total cholesterol concentrations
      (p<0.05), carriage of this allele was associated with higher HDL-C concentrations
      (p<0.05) after adjustment for associated risk factors, but not with CHD. In
      women, however, without being related to HDL-C levels, each 219K allele was
      associated with 10% higher triglycerides (TG) concentrations (p<0.05). R219K
      heterozygosity in women independently doubled (95% CI 1.00; 3.80) the odds ratio
      for CHD risk in regression models, after adjustment for several variables.
      Interaction of TG elevation (>140 mg/dL) with CHD was demonstrated in female
      219RK genotype carriers. CONCLUSION: R219 allele of the ABCA1 gene independently
      confers CHD risk in heterozygote Turkish women, not via reduced HDL-C, but
      interacting with elevated TG expressed by the 219K allele, but not in men.

PMID- 24084155
TI  - The Tomato/GFP-FLP/FRT method for live imaging of mosaic adult Drosophila
      photoreceptor cells.
AB  - The Drosophila eye is widely used as a model for studies of development and
      neuronal degeneration. With the powerful mitotic recombination technique, elegant
      genetic screens based on clonal analysis have led to the identification of
      signaling pathways involved in eye development and photoreceptor (PR)
      differentiation at larval stages. We describe here the Tomato/GFP-FLP/FRT method,
      which can be used for rapid clonal analysis in the eye of living adult
      Drosophila. Fluorescent photoreceptor cells are imaged with the cornea
      neutralization technique, on retinas with mosaic clones generated by flipase
      mediated recombination. This method has several major advantages over classical
      histological sectioning of the retina: it can be used for high-throughput
      screening and has proved an effective method for identifying the factors
      regulating PR survival and function. It can be used for kinetic analyses of PR
      degeneration in the same living animal over several weeks, to demonstrate the
      requirement for specific genes for PR survival or function in the adult fly. This
      method is also useful for addressing cell autonomy issues in developmental
      mutants, such as those in which the establishment of planar cell polarity is
      affected. 

PMID- 24084156
TI  - Copper(II) complexes of neuropeptide gamma with point mutations (S8,16A) products
      of metal-catalyzed oxidation.
AB  - To obtain the information about the influence of the serine residues (S8,S16) on
      the acid-base properties of the neuropeptide gamma, the peptide with point
      mutations (S8,16A) and its N-acetyl derivative were synthesized. Any additional
      deprotonations were not observed. It means that the presence of serine residues
      is necessary in the amino acid sequence of the neuropeptide gamma to have its
      acid-base properties. The stability constants, stoichiometry and solution
      structures of copper(II) complexes of the neuropeptide gamma mutants
      D(1)AGH(4)GQIA(8)H(9)KRH(12)KTDA(16)FVGLM(21)-NH2 (S8,16A) 2ANPG and its N-acetyl
      derivative Ac-2ANPG were determined in aqueous solution. The equilibrium and
      structural properties of copper(II) complexes have been characterized by pH
      metric, spectroscopic (UV-visible, CD, EPR) and mass spectrometric (MS) methods.
      At physiological pH7.4 the 2ANPG forms the CuH2L and CuHL complexes in
      equilibrium with 3N {NH2,betaCOO(-)-D(1),2NIm} and 4N {NH2,N(-),2NIm} binding
      sites, respectively. The exchange Ser on Ala residues does not alter the
      coordination mode of the peptide. To elucidate the products of the copper(II)
      catalyzed oxidation of 2ANPG and Ac-2ANPG the liquid chromatography-mass
      spectrometry method (LC-MS) and the Cu(II)/H2O2 as a model oxidizing system were
      employed. For solutions containing a 1:4 peptide-hydrogen peroxide molar ratio
      oxidation of the methionine residue to methionine sulphoxide was observed. For
      the 1:1:4 Cu(II)-2ANPG-H2O2 system oxidation of two His residues and cleavage of
      the G(3)H(4) peptide bond was observed, while for the 1:1:4 Cu(II)-Ac-2ANPG-H2O2
      system oxidation of three histidine residues to 2-oxohistidines was also
      observed. 

PMID- 24084157
TI  - Estimated albumin excretion rate versus urine albumin-creatinine ratio for the
      estimation of measured albumin excretion rate: derivation and validation of an
      estimated albumin excretion rate equation.
AB  - BACKGROUND: Glomerular filtration rate estimation equations use demographic
      variables to account for predicted differences in creatinine generation rate. In
      contrast, assessment of albuminuria from urine albumin-creatinine ratio (ACR)
      does not account for these demographic variables, potentially distorting
      albuminuria prevalence estimates and clinical decision making. STUDY DESIGN:
      Polynomial regression was used to derive an age-, sex-, and race-based equation
      for estimation of urine creatinine excretion rate, suitable for use in automated
      estimated albumin excretion rate (eAER) reporting. SETTING & PARTICIPANTS: The
      MDRD (Modification of Diet in Renal Disease) Study cohort (N=1,693) was used for
      equation derivation. Validation populations were the CRIC (Chronic Renal
      Insufficiency Cohort; N=3,645) and the DCCT (Diabetes Control and Complications
      Trial; N=1,179). INDEX TEST: eAER, calculated by multiplying ACR by estimated
      creatinine excretion rate, and ACR. REFERENCE TEST: Measured albumin excretion
      rate (mAER) from timed 24-hour urine collection. RESULTS: eAER estimated mAER
      more accurately than ACR; the percentages of CRIC participants with eAER within
      15% and 30% of mAER were 33% and 60%, respectively, versus 24% and 39% for ACR.
      Equivalent proportions in DCCT were 52% and 86% versus 15% and 38%. The median
      bias of ACR was -20.1% and -37.5% in CRIC and DCCT, respectively, whereas that of
      eAER was +3.8% and -9.7%. Performance of eAER also was more consistent across age
      and sex categories than ACR. LIMITATIONS: Single timed urine specimens used for
      mAER, ACR, and eAER. CONCLUSIONS: Automated eAER reporting potentially is a
      useful approach to improve the accuracy and consistency of clinical albuminuria
      assessment.

PMID- 24084158
TI  - Antimalarial activity of compounds comprising a primary benzene sulfonamide
      fragment.
AB  - Despite the urgent need for effective antimalarial drugs with novel modes of
      action no new chemical class of antimalarial drug has been approved for use since
      1996. To address this, we have used a rational approach to investigate compounds
      comprising the primary benzene sulfonamide fragment as a potential new
      antimalarial chemotype. We report the in vitro activity against Plasmodium
      falciparum drug sensitive (3D7) and resistant (Dd2) parasites for a panel of
      fourteen primary benzene sulfonamide compounds. Our findings provide a platform
      to support the further evaluation of primary benzene sulfonamides as a new
      antimalarial chemotype, including the identification of the target of these
      compounds in the parasite. 

PMID- 24084159
TI  - Inhibitory effect of oxygenated cholestan-3beta-ol derivatives on the growth of
      Mycobacterium tuberculosis.
AB  - A variety of cholestan-3beta-ol derivatives, which are oxygenated at different
      positions of the steroid ring system, were prepared and tested for their
      inhibition of the Mycobacterium tuberculosis H37Rv strain. Several compounds
      showed significant antitubercular activities with MIC90 values in the range 4-8
      MUM and low or non-detectable toxicity against mammalian cells.

PMID- 24084160
TI  - Design and synthesis of novel pyrimidone analogues as HIV-1 integrase inhibitors.
AB  - A series of novel pyrimidone analogues have been designed and synthesized as HIV
      1 integrase (IN) inhibitors. This study demonstrated that introducing a
      substituent in the N1-position of the pyrimidone scaffold does not significantly
      influence IN inhibitory activity. Molecular docking studies showed these
      compounds could occupy the IN active site and form pi-pi interactions with viral
      DNA nucleotides DC16 and DA17 to displace reactive viral DNA 3'OH and block
      intasome activity. 

PMID- 24084161
TI  - Development of dansyl-modified oligonucleotide probes responding to structural
      changes in a duplex.
AB  - We have synthesized a nonnucleoside amidite block of dansyl fluorophore to
      prepare dansyl-modified oligonucleotides (ONTs). The fluorescence intensities of
      dansyl-ONT specifically increased by the presence of adjacent guanosine residues
      but, significantly reduced in a dansyl-flipping duplex. These changes were caused
      by solvatochromism effect due to the number of guanine which is hydrophobic
      functional group and the external environment of dansyl group. The fluorescence
      intensities could be plotted as a function of the ONTs concentrations and the
      increase in the fluorescence was observed to equimolar concentrations of target
      DNA. This duplex exhibited higher melting temperature relative to the
      corresponding duplexes containing other base pairs. Similar changes in
      fluorescence could be detected upon hybridization with complementary RNAs. Thus,
      the dansyl-modified ONTs provide sequence specific fluorescent probe of DNA and
      RNA. 

PMID- 24084162
TI  - Nutritional signals and reproduction.
AB  - There is extensive evidence that nutrition influences reproductive function in
      various mammalian species (agricultural animals, rodents and human). However, the
      mechanisms underlying the relationship between nutrition, energy metabolism and
      reproductive function are poorly understood. This review considers nutrient
      sensors as a molecular link between food molecules and consequences for female
      and male fertility. It focuses on the roles and the molecular mechanisms of some
      of the relevant hormones, such as insulin and adipokines, and of energy
      substrates (glucose, fatty acids and amino acids), in the gonadotropic axis
      (central nervous system and gonads). A greater understanding of the interactions
      between nutrition and fertility is required for both better management of the
      physiological processes and the development of new molecules to prevent or cure
      metabolic diseases and their consequences for fertility. 

PMID- 24084163
TI  - Transcriptomic and epigenetic changes in early liver steatosis associated to
      obesity: effect of dietary methyl donor supplementation.
AB  - Non-alcoholic fatty liver disease is a primary hepatic manifestation of obesity
      and an important adverse metabolic syndrome trait. Animal models of diet-induced
      obesity promote liver fat accumulation putatively associated with alterations in
      epigenetic profile. Dietary methyl donor-supplementation may protect against this
      disturbance during early developmental stages affecting the molecular basis of
      gene regulation. The aim of this study was to investigate the transcriptomic and
      epigenetic mechanisms implicated in liver fat accumulation as a result of an
      obesogenic diet and the putative preventive role of dietary methyl donors. Forty
      eight male Wistar rats were assigned into four dietary groups for 8 weeks;
      control, control methyl-donor-supplemented with a dietary cocktail containing
      betaine, choline, vitamin B12 and folic acid, high-fat-sucrose and high-fat
      sucrose methyl-donor-supplemented. Liver fat accumulation induced by a HFS diet
      was prevented by methyl donor supplementation in HFS-fed animals. A liver mRNA
      microarray, subsequently validated by real time-qPCR, showed modifications in
      some biologically relevant genes involved in obesity development and lipid
      metabolism (Lepr, Srebf2, Agpat3 and Esr1). Liver global DNA methylation was
      decreased by methyl donor supplementation in control-fed animals. Methylation
      levels of specific CpG sites from Srebf2, Agpat3 and Esr1 promoter regions showed
      changes due to the obesogenic diet and the supplementation with methyl donors.
      Interestingly, Srebf2 CpG23_24 methylation levels (-167 bp and -156 bp with
      respect to the transcriptional start site) correlated with HDLc plasma levels,
      whereas Esr1 CpG14 (-2623 bp) methylation levels were associated with body and
      liver weights and fat content. Furthermore HFS diet-induced liver fat
      accumulation was prevented by methyl donor supplementation. In conclusion, both
      obesogenic diet and methyl donor supplementation modified the mRNA hepatic
      profile as well as the methylation of specific gene promoters and total DNA.

PMID- 24084164
TI  - A multianalyte electrochemical immunosensor based on patterned carbon nanotubes
      modified substrates for detection of pesticides.
AB  - A novel multianalyte electrochemical immunosensor based on the assembly of
      patterned SWNTs on glassy carbon (GC) substrates was developed for simultaneous
      detection of endosulfan and paraoxon. Based on aryldiazonium salt chemistry,
      forest of SWNTs can be patterned on GC substrates by C3C bonding using micro
      contact printing (MCP), which provides an interface showing efficient electron
      transfer between biomolecules and electrodes. Then redox molecules FDMA and PQQ
      can be attached to the SWNTs, respectively followed by the attachment of specific
      epitopes and antibodies. The modified sensing surfaces were characterized by XPS,
      SEM, AFM and electrochemistry. Based on the current change of specific redox
      probes, the fabricated immunosensor array can be used for simultaneous detection
      of endosulfan and paraoxon by a displacement assay. In phosphate buffer solution
      (50mM, pH 7.0), there is a linear relationship between electrochemical signal of
      FDMA and the concentration of endosulfan over the range of 0.05-100 ppb with a
      detection limit of 0.05ppb; the linear range between electrochemical signal of
      PQQ and the concentration of paraoxon is 2-2500 ppb with a detection limit of 2
      ppb. The immunosensor array demonstrates high repeatability, reproducibility,
      stability and selectivity for the detection of endosulfan and paraoxon.

PMID- 24084165
TI  - A new method for detecting cerebral hemorrhage in rabbits by magnetic inductive
      phase shift.
AB  - Cerebral hemorrhage, which is an important clinical problem, is often monitored
      and studied using expensive devices, such as magnetic resonance imaging (MRI) and
      positron emission tomography (PET) that are unavailable in economically
      underdeveloped regions. Magnetic induction tomography (MIT) is a new type of non
      contact, non-invasive, and low-cost detection technology, and exhibits prospects
      for wide application, especially for the detection of brain diseases. However,
      the previous studies on MIT have focused on laboratory models and rarely on in
      vivo applications because the induced signals produced by biological tissues are
      notably weak. Based on the symmetry between the two brain hemispheres and the
      fact that a local brain hemorrhage will not affect the contra-lateral hemisphere,
      a symmetric cancellation-type sensor detection system, which is characterized by
      one excitation coil and two receiving coils, was designed to improve the
      detection sensitivity of MIT. This method was subsequently used to detect the
      occurrence of cerebral hematomas in rabbits. The average phase drift induced by a
      3-ml injection of autologous blood was 1.885 degrees , which is a fivefold
      improvement compared with the traditional single excitation coil and single
      receiving coil method. The results indicate that this system has high sensitivity
      and anti-interference ability and high practical value. 

PMID- 24084166
TI  - Aluminium induced oxidative stress results in decreased mitochondrial biogenesis
      via modulation of PGC-1alpha expression.
AB  - The present investigation was carried out to elucidate a possible molecular
      mechanism related to the effects of aluminium-induced oxidative stress on various
      mitochondrial respiratory complex subunits with special emphasis on the role of
      Peroxisome proliferator activated receptor gamma co-activator 1alpha (PGC-1alpha)
      and its downstream targets i.e. Nuclear respiratory factor-1(NRF-1), Nuclear
      respiratory factor-2(NRF-2) and Mitochondrial transcription factor A (Tfam) in
      mitochondrial biogenesis. Aluminium lactate (10mg/kgb.wt./day) was administered
      intragastrically to rats for 12 weeks. After 12 weeks of exposure, we found an
      increase in ROS levels, mitochondrial DNA oxidation and decrease in citrate
      synthase activity in the Hippocampus (HC) and Corpus striatum (CS) regions of rat
      brain. On the other hand, there was a decrease in the mRNA levels of the
      mitochondrial encoded subunits-NADH dehydrogenase (ND) subunits i.e. ND1, ND2,
      ND3, Cytochrome b (Cytb), Cytochrome oxidase (COX) subunits i.e. COX1, COX3, ATP
      synthase (ATPase) subunit 6 along with reduced expression of nuclear encoded
      subunits COX4, COX5A, COX5B of Electron transport chain (ETC). Besides, a
      decrease in mitochondrial DNA copy number and mitochondrial content in both
      regions of rat brain was observed. The PGC-1alpha was down-regulated in aluminium
      treated rats along with NRF-1, NRF-2 and Tfam, which act downstream from PGC
      1alpha in aluminium treated rats. Electron microscopy results revealed a
      significant increase in the mitochondrial swelling, loss of cristae, chromatin
      condensation and decreases in mitochondrial number in case of aluminium treated
      rats as compared to control. So, PGC-1alpha seems to be a potent target for
      aluminium neurotoxicity, which makes it an almost ideal target to control or
      limit the damage that has been associated with the defective mitochondrial
      function seen in neurodegenerative diseases.

PMID- 24084167
TI  - Faces of a changing climate: semi-quantitative multi-mycotoxin analysis of grain
      grown in exceptional climatic conditions in Norway.
AB  - Recent climatological research predicts a significantly wetter climate in
      Southern Norway as a result of global warming. Thus, the country has already
      experienced unusually wet summer seasons in the last three years (2010-2012). The
      aim of this pilot study was to apply an existing multi-analyte LC-MS/MS method
      for the semi-quantitative determination of 320 fungal and bacterial metabolites
      in Norwegian cereal grain samples from the 2011 growing season. Such knowledge
      could provide important information for future survey and research programmes in
      Norway. The method includes all regulated and well-known mycotoxins such as
      aflatoxins, trichothecenes, ochratoxin A, fumonisins and zearalenone. In
      addition, a wide range of less studied compounds are included in the method,
      e.g., Alternaria toxins, ergot alkaloids and other metabolites produced by fungal
      species within Fusarium, Penicillium and Aspergillus. Altogether, 46 metabolites,
      all of fungal origin, were detected in the 76 barley, oats and wheat samples. The
      analyses confirmed the high prevalence and relatively high concentrations of type
      A and -B trichothecenes (e.g., deoxynivalenol up to 7230 ug/kg, HT-2 toxin up to
      333 ug/kg). Zearalenone was also among the major mycotoxins detected (maximum
      concentration 1670 ug/kg). Notably, several other Fusarium metabolites such as
      culmorin, 2-amino-14,16-dimethyloctadecan-3-ol and avenacein Y were co-occurring.
      Furthermore, the most prevalent Alternaria toxin was alternariol with a maximum
      concentration of 449 ug/kg. A number of Penicillium and Aspergillus metabolites
      were also detected in the samples, e.g., sterigmatocystin in concentrations up to
      20 ug/kg. 

PMID- 24084168
TI  - Experience with sugar modifies behavioral but not taste-evoked medullary
      responses to sweeteners in mice.
AB  - Dietary exposure to sugars increases the preference for and intake of sugar
      solutions in mice. We used brief-access lick tests and multiunit
      electrophysiological recordings from the nucleus of the solitary tract (NST) to
      investigate the role of taste in diet-induced changes in sucrose responsiveness.
      We exposed C57BL/6J (B6) and 129X1/SvJ (129) mice to either a sucrose diet (chow,
      water, and a 500mM sucrose solution) or a control diet (chow and water) for 3
      days. In B6 mice, exposure to the sucrose diet decreased the appetitive response
      (i.e., number of trials initiated) but had no effect on the consummatory response
      (i.e., rate of licking) to 500mM sucrose and 20mM saccharin. In 129 mice,
      exposure to the sucrose diet increased the appetitive response but had no effect
      on the consummatory response to the sweetener solutions. In the NST recordings,
      the B6 mice exhibited larger multiunit responses to sweeteners than 129 mice, but
      there was no effect of the sucrose diet in either strain. Our results indicate
      that sucrose exposure alters the appetitive response of B6 and 129 mice to
      sweeteners in diametrically opposed ways and that these changes are mediated by
      structures in the gustatory neuraxis above the NST (e.g., ventral forebrain). 

PMID- 24084169
TI  - Specificity in suppression of SOS expression by recA4162 and uvrD303.
AB  - Detection and repair of DNA damage is essential in all organisms and depends on
      the ability of proteins recognizing and processing specific DNA substrates. In E.
      coli, the RecA protein forms a filament on single-stranded DNA (ssDNA) produced
      by DNA damage and induces the SOS response. Previous work has shown that one type
      of recA mutation (e.g., recA4162 (I298V)) and one type of uvrD mutation (e.g.,
      uvrD303 (D403A, D404A)) can differentially decrease SOS expression depending on
      the type of inducing treatments (UV damage versus RecA mutants that
      constitutively express SOS). Here it is tested using other SOS inducing
      conditions if there is a general feature of ssDNA generated during these
      treatments that allows recA4162 and uvrD303 to decrease SOS expression. The SOS
      inducing conditions tested include growing cells containing temperature-sensitive
      DNA replication mutations (dnaE486, dnaG2903, dnaN159, dnaZ2016 (at 37 degrees
      C)), a del(polA)501 mutation and induction of Double-Strand Breaks (DSBs).
      uvrD303 could decrease SOS expression under all conditions, while recA4162 could
      decrease SOS expression under all conditions except in the polA strain or when
      DSBs occur. It is hypothesized that recA4162 suppresses SOS expression best when
      the ssDNA occurs at a gap and that uvrD303 is able to decrease SOS expression
      when the ssDNA is either at a gap or when it is generated at a DSB (but does so
      better at a gap). 

PMID- 24084170
TI  - Slow accumulation of mutations in Xpc-/- mice upon induction of oxidative stress.
AB  - XPC is one of the key DNA damage recognition proteins in the global genome repair
      route of the nucleotide excision repair (NER) pathway. Previously, we
      demonstrated that NER-deficient mouse models Xpa(-/-) and Xpc(-/-) exhibit a
      divergent spontaneous tumor spectrum and proposed that XPC might be functionally
      involved in the defense against oxidative DNA damage. Others have mechanistically
      dissected several functionalities of XPC to oxidative DNA damage sensitivity
      using in vitro studies. XPC has been linked to regulation of base excision repair
      (BER) activity, redox homeostasis and recruitment of ATM and ATR to damage sites,
      thereby possibly regulating cell cycle checkpoints and apoptosis. XPC has
      additionally been implicated in recognition of bulky (e.g. cyclopurines) and non
      bulky DNA damage (8-oxodG). However, the ultimate contribution of the XPC
      functionality in vivo in the oxidative DNA damage response and subsequent
      mutagenesis process remains unclear. Our study indicates that Xpc(-/-) mice, in
      contrary to Xpa(-/-) and wild type mice, have an increased mutational load upon
      induction of oxidative stress and that mutations arise in a slowly accumulative
      fashion. The effect of non-functional XPC in vivo upon oxidative stress exposure
      appears to have implications in mutagenesis, which can contribute to the
      carcinogenesis process. The levels and rate of mutagenesis upon oxidative stress
      correlate with previous findings that lung tumors in Xpc(-/-) mice overall arise
      late in the lifespan and that the incidence of internal tumors in XP-C patients
      is relatively low in comparison to skin cancer incidence. 

PMID- 24084172
TI  - Accelerometer-determined sedentary and physical activity estimates among older
      adults with diabetes: considerations by demographic and comorbidity
      characteristics.
AB  - Understanding of the objectively measured physical activity (PA) and sedentary
      patterns of adults with diabetes at the population level is currently limited.
      Therefore, the purpose of this study was to report accelerometer-determined PA
      and sedentary patterns among a national sample of U.S. adults with and without
      evidence of diabetes and to also explore differences across other comorbidity
      characteristics. Data from the 2003-2006 National Health and Nutrition
      Examination Survey were used. Four hundred seven participants had evidence of
      diabetes (mean age = 73.4 years), and 1,346 did not have diabetes (mean age =
      74.3 years). Results showed that few older adults meet PA guidelines; the
      majority of their time is spent in sedentary activities; very few engage in more
      light-intensity PA than sedentary behavior; and older adults with multiple
      comorbidities engage in less PA and more sedentary behavior than their
      counterparts. The development and implementation of feasible, effective PA
      programs for older adults with multiple comorbidities are warranted.

PMID- 24084173
TI  - Dietary restriction in the periconceptional period in normal-weight or obese ewes
      results in increased abundance of angiotensin-converting enzyme (ACE) and
      angiotensin type 1 receptor (AT1R) in the absence of changes in ACE or AT1R
      methylation in the adrenal of the offspring.
AB  - Exposure to dietary restriction during the periconceptional period in either
      normal or obese ewes results in increased adrenal growth and a greater cortisol
      response to stress in the offspring, but the mechanisms that programme these
      changes are not fully understood. Activation of the angiotensin type 1 receptor
      (AT1R) has been demonstrated to stimulate adrenal growth and steroidogenesis. We
      have used an embryo transfer model in the sheep to investigate the effects of
      exposure to dietary restriction in normal or obese mothers from before and 1 week
      after conception on the methylation status, expression, abundance and
      localisation of key components of the renin-angiotensin system (RAS) in the
      adrenal of post-natal lambs. Maternal dietary restriction in normal or obese ewes
      during the periconceptional period resulted in an increase in angiotensin
      converting enzyme (ACE) and AT1R abundance in the absence of changes in the
      methylation status or mRNA expression of ACE and AT1R in the adrenal of the
      offspring. Exposure to maternal obesity alone also resulted in an increase in
      adrenal AT1R abundance. There was no effect of maternal dietary restriction or
      obesity on ACE2 and AT2R or on ERK, calcium/calmodulin-dependent kinase II
      abundance, and their phosphorylated forms in the lamb adrenal. Thus, weight loss
      around the time of conception, in both normal-weight and obese ewes, results in
      changes within the intra-adrenal RAS consistent with increased AT1R activation.
      These changes within the intra-adrenal RAS system may contribute to the greater
      adrenal stress response following exposure to signals of adversity in the
      periconceptional period. 

PMID- 24084171
TI  - DNA polymerases beta and lambda do not directly affect Ig variable region somatic
      hypermutation although their absence reduces the frequency of mutations.
AB  - During somatic hypermutation (SHM) of antibody variable (V) region genes,
      activation-induced cytidine deaminase (AID) converts dC to dU, and dUs can either
      be excised by uracil DNA glycosylase (UNG), by mismatch repair, or replicated
      over. If UNG excises the dU, the abasic site could be cleaved by AP-endonuclease
      (APE), introducing the single-strand DNA breaks (SSBs) required for generating
      mutations at A:T bp, which are known to depend upon mismatch repair and DNA Pol
      eta. DNA Pol beta or lambda could instead repair the lesion correctly. To assess
      the involvement of Pols beta and lambda in SHM of antibody genes, we analyzed
      mutations in the VDJh4 3' flanking region in Peyer's patch germinal center (GC) B
      cells from polbeta(-/-)pollambda(-/-), pollambda(-/-), and polbeta(-/-) mice. We
      find that deficiency of either or both polymerases results in a modest but
      significant decrease in V region SHM, with Pol beta having a greater effect, but
      there is no effect on mutation specificity, suggesting they have no direct role
      in SHM. Instead, the effect on SHM appears to be due to a role for these enzymes
      in GC B cell proliferation or viability. The results suggest that the BER pathway
      is not important during V region SHM for generating mutations at A:T bp.
      Furthermore, this implies that most of the SSBs required for Pol eta to enter and
      create A:T mutations are likely generated during replication instead. These
      results contrast with the inhibitory effect of Pol beta on mutations at the Ig
      SMU locus, SMU DSBs and class switch recombination (CSR) reported previously. We
      show here that B cells deficient in Pol lambda or both Pol beta and lambda
      proliferate normally in culture and undergo slightly elevated CSR, as shown
      previously for Pol beta-deficient B cells. 

PMID- 24084174
TI  - Seeing more clearly through the fog of encephalopathy.
AB  - Patients with acute confusional states (often referred to as encephalopathy or
      delirium) pose diagnostic and management challenges for treating physicians.
      Encephalopathy is associated with a high morbidity and mortality rate, and the
      diagnosis rests on clinical grounds but may also be supported by the finding of
      electroencephalographic (EEG) evidence for diffuse cerebral dysfunction. The
      myriad cerebral transmitter and metabolic disruptions are generated by systemic
      organ system failures, principal among which are those of the liver, kidneys,
      lungs, heart, and endocrine system, along with the effects of exogenous toxins
      and medications. In most cases, several of these organ failures together
      contribute to the confusional state, frequently in the context of a diffuse
      cerebral atrophy that affects the aging brain. This special issue of the Journal
      of Clinical Neurophysiology is dedicated to exploring the electrophysiology of
      these conditions. It reviews the pathophysiology, psychiatric manifestations,
      clinical and imaging correlations of the many causes and types of encephalopathy.
      A literature review of the EEG abnormalities in the various types of
      encephalopathy provides an overview that ranges from paraneoplastic causes,
      through organ system failures, postcardiorespiratory arrest, to postoperative
      delirium. The issue is supplemented by tables of relevant clinical correlations,
      graphs, Venn diagrams, and the use of mathematical modeling used to explain how
      defects in the neuronal interplay might generate the EEG patterns seen in
      encephalopathy. We hope that this assembly will act as a springboard for further
      discussion and investigation into the EEG underpinnings, clinical correlations,
      diagnosis. and prognostication of these common and morbid disturbances of brain
      function.

PMID- 24084175
TI  - Pathophysiology of encephalopathy and delirium.
AB  - Effective development of targeted therapies to prevent and treat delirium
      requires an understanding of the underlying physiologic processes. Historically,
      delirium has been considered a reflection of diffuse cerebral metabolic
      insufficiency, which may be a result of some combination of abnormal blood flow,
      abnormal energy metabolism, abnormal neurotransmission, and abnormal cellular
      maintenance processes. Perspectives on the pathophysiology underlying hepatic
      encephalopathy, sepsis-associated encephalopathy, critical illness delirium, and
      alcohol withdrawal delirium are discussed. Given the diverse etiologic
      mechanisms, it is likely that the pathophysiology underlying delirium is also
      quite diverse. Additional investigation is required to identify therapeutic
      targets for prevention and treatment.

PMID- 24084176
TI  - Delirium: definition, epidemiology, and diagnosis.
AB  - This article serves to (1) review the relationship of the terms "delirium" and
      "encephalopathy," (2) describe delirium as defined in current diagnostic systems,
      (3) summarize the epidemiology and theories of pathogenesis, (4) review clinical
      diagnostic approaches, and (5) highlight the history using EEG in the study of
      delirium in the psychiatric literature. Delirium is an important medical syndrome
      with significant implications; there is continued need for better physiologic
      measures of the underlying brain dysfunction.

PMID- 24084177
TI  - Clinical and electroencephalographic correlates of acute encephalopathy.
AB  - The term encephalopathy encompasses a wide variety of syndromes caused by a large
      number of different toxic, metabolic, and degenerative derangements. Despite
      advances in intensive medical care and new diagnostic procedures, encephalopathy
      remains a frequent and underrecognized critical medical condition with high
      morbidity and mortality. Electroencephalography (EEG) enables rapid bedside
      electrophysiological measurements of brain dysfunction and complements clinical
      and neuroimaging assessment of encephalopathic patients. Both progressive slowing
      of EEG background activity with increasing cerebral compromise and decreased EEG
      reactivity to external stimuli provide important diagnostic and prognostic
      information. The aim of this review was to provide an overview of the diagnostic
      and prognostic value of EEG in encephalopathic patients.

PMID- 24084178
TI  - Encephalopathy of infection and systemic inflammation.
AB  - This review will discuss several intracranial infections and sepsis-associated
      encephalopathy. Intracranial infections and inflammation of interest to the
      neurologist and EEG technicians include viral and autoimmune encephalitides;
      bacterial, fungal, and other meningitides; cerebritis; and brain abscess and
      subdural empyema. Sepsis-associated encephalopathy refers to a diffuse brain
      dysfunction secondary to infection that is principally located outside of the
      central nervous system. It is much more common than all of the intracranial
      infections put together, at least for adults in Western society. It probably
      involves a number of mechanisms that are not mutually exclusive and likely vary
      from patient to patient. Morbidity and mortality are directly related to the
      severity of SAE. The earliest features of SAE are delirium and mild EEG slowing;
      it is crucial to recognize these early features and to search for and treat the
      underlying infection promptly to reduce mortality and morbidity.

PMID- 24084179
TI  - Traumatic encephalopathy.
AB  - Traumatic brain injury is the leading cause of death and disability among young
      adults. Clinical evaluation is of limited value in the assessment of patients
      with traumatic brain injury and is often inaccurate in determining the extent of
      brain damage. Neurophysiological techniques and neuroimaging can provide valuable
      prognostic information and are useful in monitoring for seizures and other causes
      of secondary brain damage and in tracking the effects of therapy. More recently,
      cognitive electrophysiology and functional magnetic resonance imaging have shown
      that many patients clinically deemed to be in vegetative or in minimally
      conscious states are, in fact, aware. This opens new frontiers for further
      research into establishing communication with otherwise unresponsive patients.

PMID- 24084180
TI  - Overlap of encephalopathies and epileptic seizures.
AB  - Encephalopathies and epileptic seizures are usually distinct, but important,
      components of neurologic illnesses. Each may cause altered mental status and
      behavior, but by different mechanisms. Encephalopathies involve widespread,
      usually inhibitory, brain dysfunction. Epileptic seizures usually consist of
      paroxysmal rhythmic excitatory brain activity that produces abnormal function.
      Some syndromes include both. Sometimes, an encephalopathy may cause seizures, and
      many patients are encephalopathic postictally. Nonconvulsive seizures and
      nonconvulsive status epilepticus may be difficult to distinguish from
      encephalopathies. The EEG is crucial in the distinction, but epileptiform
      features may appear in either. The greatest area of overlap and difficulty in
      diagnosis is probably that following clinical seizures, when a patient may have a
      postictal encephalopathy or may still be seizing.

PMID- 24084181
TI  - EEG patterns in hypoxic encephalopathies (post-cardiac arrest syndrome):
      fluctuations, transitions, and reactions.
AB  - In patients with coma resulting from hypoxic encephalopathy (e.g., after cardiac
      arrest), the EEG may reflect the severity of brain dysfunction, although the
      exact relationship among the EEG changes, the extent of neuronal damage, and
      consequent prognosis is still under study. Many prognostications are based on
      particular EEG patterns at a time point, such as burst suppression or generalized
      periodic discharges, but with sequential, repeated, or with prolonged or
      continuous EEG monitoring, it has become increasingly clear that more information
      might be gleaned from EEG pattern changes over time. Short-term fluctuations (as
      opposed to permanent transitions), or preserved reactions to exogenous stimuli,
      have to be differentiated. This review presents many of the typical postanoxic
      EEG patterns, along with their evolution over time. This preliminary report
      illustrates the temporal dynamic changes of EEG over time. It is hoped that it
      will act as a starting point for prospective and systematic investigation to test
      whether EEG evolution and transitions add diagnostic and prognostic value.

PMID- 24084182
TI  - Electroencephalography of autoimmune limbic encephalopathy.
AB  - There is an increasing recognition of autoimmune limbic encephalopathy with the
      hope for earlier diagnosis and expedited and improved treatment. Although
      antibody testing remains the definitive clinical diagnostic feature, the
      presentation of a rapid dementia, behavioral changes, and seizures leads to
      investigation using cerebral imaging, electroencephalography, and cerebrospinal
      fluid to confirm the diagnosis and also to exclude similar disorders. The
      electroencephalographer may be asked to comment on the types of
      electroencephalography abnormality and provide input toward the diagnosis of
      limbic encephalopathy. This article reviews the literature on limbic
      paraneoplastic and nonparaneoplastic encephalopathies, providing descriptions and
      examples of the electroencephalography findings. Typically, there are patterns of
      slow theta and delta activity and different patterns of temporal and frontal
      epileptic activity.

PMID- 24084184
TI  - Neuroimaging correlates of acute encephalopathy.
AB  - Acute encephalopathies arise as a result of various contributions from infections
      or toxic, metabolic, and/or structural cerebral derangements. With the variety of
      clinical presentations, neurologic examination, electroencephalography (EEG), and
      imaging may not identify specific etiologies, but in combination, they can offer
      guidance regarding underlying causes. Among several different neuroimaging
      techniques, cerebral computed tomography and brain magnetic resonance imaging are
      most frequently used for diagnosis, treatment monitoring, and prognostication in
      acute brain dysfunction. This review compiles the most common and typical
      features of head computed tomography and magnetic resonance imaging and presents
      the clinical and EEG associations in adult patients with different types of acute
      encephalopathy.

PMID- 24084185
TI  - Quantitative EEG in hospital encephalopathy: review and microstate analysis.
AB  - Hospital-acquired encephalopathy is a widely prevalent disorder. The quantitative
      changes in EEG associated with this condition have long been noted, including
      slowing of the background frequency and changes in the frequency band power. EEG
      has had limited clinical use, despite its ability to continuously track clinical
      severity. We review the development of the use of EEG and particularly
      quantitative EEG in the assessment of hospital-acquired encephalopathy. Recent
      advances in EEG technology have included network and microstate analyses, and
      continuous EEG monitoring, leading to renewed interest in the use of quantitative
      EEG. We describe the development of microstate analysis that has allowed novel
      quantitative analysis of the resting state background. We examined the
      microstates of 16 inpatients with encephalopathy and 20 control patients. The
      global variance explained by the four standard resting microstates was smaller in
      patients with encephalopathy. This suggests a decrease in microstate stability,
      indicating a breakdown in the resting state network dynamics. Modern analysis and
      acquisition techniques hold the promise of renewed interest in quantitative EEG
      techniques in the assessment of hospital-acquired encephalopathy.

PMID- 24084186
TI  - The EEG of tropical encephalopathies.
AB  - In addition to encountering most of the conditions treated by clinicians in the
      West, clinicians in the tropics are faced with unique tropical encephalopathies.
      These are largely but not entirely infectious in nature. Despite the relatively
      low cost of EEG technology, it remains unavailable in many low-income tropical
      settings even at the tertiary care level. Where available, the EEG recordings and
      interpretation are often of unacceptable quality. Nonetheless, there are existing
      data on the EEG patterns seen in malaria and a number of tropical viral,
      bacterial, and parasitic infestations.

PMID- 24084183
TI  - Electroencephalography of encephalopathy in patients with endocrine and metabolic
      disorders.
AB  - Patients with acute alteration in mental status from encephalopathy because of
      underlying metabolic-toxic or endocrine abnormalities are frequently seen in the
      acute hospital setting. A rapid diagnosis and correction of the underlying cause
      is essential as a prolonged state of encephalopathy portends a poor outcome.
      Correct diagnosis and management remain challenging because several
      encephalopathies may present similarly, and further laboratory, imaging, or other
      testing may not always reveal the underlying cause. EEG provides rapid additional
      information on the encephalopathic patient. It may help establish the diagnosis
      and is indispensable for identifying nonconvulsive status epilepticus, an
      important possible complication in this context. The EEG may assist the clinician
      in gauging the severity of brain dysfunction and may aid in predicting outcome.
      This review summarizes the current knowledge on EEG findings in selected
      metabolic and endocrine causes of encephalopathy and highlights distinct EEG
      features associated with particular etiologies.

PMID- 24084187
TI  - EEG patterns in acute pediatric encephalopathies.
AB  - EEG patterns in pediatric encephalopathy are largely nonspecific and may be seen
      in a wide variety of pathologies. However, EEG can play a valuable role in
      helping to assess the severity and ultimate prognosis in pediatric
      encephalopathies. This review article considers three of the most common forms of
      pediatric encephalopathy encountered in pediatric critically care units,
      including hypoxic ischemic encephalopathy, central nervous system infections, and
      metabolic encephalopathies. Because EEG is being used with increasing frequency
      in critically ill children, the value of EEG monitoring in encephalopathic
      patients continues to evolve.

PMID- 24084188
TI  - Neural network modeling of EEG patterns in encephalopathy.
AB  - The EEG is an accessible tool for detecting encephalopathy, which usually
      manifests as delirium and sometimes as coma. Several disturbances have been
      described in the EEG of patients with encephalopathy, including diffuse slowing
      and periodic discharges. The pathophysiology of these EEG alterations, however,
      is poorly understood. This article shows that simulating activity of large
      populations of neurons, using neural mass models and neural network analysis, may
      increase our understanding of EEG disturbances in encephalopathy. We provide a
      brief introduction on the concepts of neural mass modeling and graph theoretical
      network analysis, and insights from this approach in previous work on neurologic
      disease, with a focus on encephalopathy. Finally, we speculate how anatomically
      coupled neural mass modeling combined with network analysis could provide new
      insights in pathophysiology of encephalopathy.

PMID- 24084189
TI  - Akt inhibition enhances the cytotoxic effect of apigenin in combination with
      PLX4032 in anaplastic thyroid carcinoma cells harboring BRAFV600E.
AB  - Aim of the present study was to evaluate the effect of apigenin in combination
      with BRAFV600E inhibitor PLX4032 on cell survival, and to investigate the
      influence of Akt inhibition on the combined effect of apigenin and PLX4032 in ATC
      cells harboring BRAFV600E. In 8505C and FRO cells harboring BRAFV600E, after
      treatment of apigenin and PLX4032, the cell viability decreased, and the
      percentage of dead cells increased in a time- and concentration-dependent manner,
      respectively. In apigenin- and PLX4032- treated cells, compared with apigenin
      alone-treated cells, the cell viability was lessened, and the percentage of dead
      cells was multiplied. In the addition of PLX4032 to apigenin, compared with the
      treatment of apigenin alone, the protein levels of cleaved PARP-1 and cleaved
      caspase-3 were elevated, and phospho-ERK protein levels were reduced, and the
      protein levels of total ERK, c-Myc, BRAF, phospho-Akt, phospho-p70S6K and phospho
      4EBP1 were not varied. Compared with the treatment of PLX4032 alone,
      phosphop70S6K protein levels were reduced, and the other protein levels were not
      altered. Phospho-ERK protein levels were reduced only in 8505C cells. Under the
      co-treatment of apigenin and PLX4032, administration of the PI3K inhibitor
      wortmannin further decreased the cell viability, and increased the percentage of
      dead cells. In conclusion, our results suggest that PLX4032 augments apigenin
      induced cytotoxicity in ATC cells harboring BRAFV600E. Moreover, Akt suppression
      potentiates the combined effect of apigenin and PLX4032 in ATC cells harboring
      BRAFV600E. 

PMID- 24084191
TI  - Isolation and chemical characterization of lipid A from gram-negative bacteria.
AB  - Lipopolysaccharide (LPS) is the major cell surface molecule of gram-negative
      bacteria, deposited on the outer leaflet of the outer membrane bilayer. LPS can
      be subdivided into three domains: the distal O-polysaccharide, a core
      oligosaccharide, and the lipid A domain consisting of a lipid A molecular species
      and 3-deoxy-D-manno-oct-2-ulosonic acid residues (Kdo). The lipid A domain is the
      only component essential for bacterial cell survival. Following its synthesis,
      lipid A is chemically modified in response to environmental stresses such as pH
      or temperature, to promote resistance to antibiotic compounds, and to evade
      recognition by mediators of the host innate immune response. The following
      protocol details the small- and large-scale isolation of lipid A from gram
      negative bacteria. Isolated material is then chemically characterized by thin
      layer chromatography (TLC) or mass-spectrometry (MS). In addition to matrix
      assisted laser desorption/ionization-time of flight (MALDI-TOF) MS, we also
      describe tandem MS protocols for analyzing lipid A molecular species using
      electrospray ionization (ESI) coupled to collision induced dissociation (CID) and
      newly employed ultraviolet photodissociation (UVPD) methods. Our MS protocols
      allow for unequivocal determination of chemical structure, paramount to
      characterization of lipid A molecules that contain unique or novel chemical
      modifications. We also describe the radioisotopic labeling, and subsequent
      isolation, of lipid A from bacterial cells for analysis by TLC. Relative to MS
      based protocols, TLC provides a more economical and rapid characterization
      method, but cannot be used to unambiguously assign lipid A chemical structures
      without the use of standards of known chemical structure. Over the last two
      decades isolation and characterization of lipid A has led to numerous exciting
      discoveries that have improved our understanding of the physiology of gram
      negative bacteria, mechanisms of antibiotic resistance, the human innate immune
      response, and have provided many new targets in the development of antibacterial
      compounds. 

PMID- 24084192
TI  - Peripheral organ doses from radiotherapy for heterotopic ossification of non-hip
      joints: is there a risk for radiation-induced malignancies?
AB  - Radiotherapy, used for heterotopic ossification (HO) management, may increase
      radiation risk to patients. This study aimed to determine the peripheral dose to
      radiosensitive organs and the associated cancer risks due to radiotherapy of HO
      in common non-hip joints. A Monte Carlo model of a medical linear accelerator
      combined with a mathematical phantom representing an average adult patient were
      employed to simulate radiotherapy for HO with standard AP and PA fields in the
      regions of shoulder, elbow and knee. Radiation dose to all out-of-field
      radiosensitive organs defined by the International Commission on Radiological
      Protection was calculated. Cancer induction risk was estimated using organ
      specific risk coefficients. Organ dose change with increased field dimensions was
      also evaluated. Radiation therapy for HO with a 7 Gy target dose in the sites of
      shoulder, elbow and knee, resulted in the following equivalent organ dose ranges
      of 0.85-62 mSv, 0.28-1.6 mSv and 0.04-1.6 mSv, respectively. Respective ranges
      for cancer risk were 0-5.1, 0-0.6 and 0-1.3 cases per 10(4) persons. Increasing
      the field size caused an average increase of peripheral doses by 15-20%.
      Individual organ dose increase depends upon the primary treatment site and the
      distance between organ of interest and treatment volume. Relatively increased
      risks of more than 1 case per 10,000 patients were found for skin, breast and
      thyroid malignancies after treatment in the region of shoulder and for skin
      cancer following elbow irradiation. The estimated risk for inducing any other
      malignant disease ranges from negligible to low.

PMID- 24084190
TI  - Intra-articular injection of the selective cyclooxygenase-2 inhibitor meloxicam
      (Mobic) reduces experimental osteoarthritis and nociception in rats.
AB  - OBJECTIVE: To study the effect of intra-articular injection of meloxicam (Mobic)
      on the development of osteoarthritis (OA) in rats and examine concomitant changes
      in nociceptive behavior and the expression of mitogen-activated protein kinases
      (MAPKs) in articular cartilage chondrocytes. METHODS: OA was induced in Wistar
      rats by right anterior cruciate ligament transection (ACLT); the left knee was
      not treated. The OA + meloxicam (1.0 mg) group was injected intra-articularly in
      the ACLT knee with 1.0 mg of meloxicam once a week for 5 consecutive weeks
      starting 5 weeks after ACLT. The OA + meloxicam (0.25 mg) group was treated
      similarly with 0.25 mg meloxicam. The sham group underwent arthrotomy only and
      received vehicle of 0.1 mL sterile 0.9% saline injections, whereas the naive rats
      in meloxicam-only groups were treated similarly with 1.0- and 0.25-mg meloxicam.
      Nociception was measured as secondary mechanical allodynia and hind paw weight
      bearing distribution at before (pre-) and 5, 10, 15, and 20 weeks post-ACLT.
      Histopathology of the cartilage and synovia was examined 20 weeks after ACLT.
      Immunohistochemical analysis was performed to examine the effect of meloxicam on
      MAPKs (p38, c-Jun N-terminal kinase (JNK), and extracellular signal-regulated
      kinase (ERK)) expression in the articular cartilage chondrocytes. RESULTS: OA
      rats receiving intra-articular meloxicam treatment showed significantly less
      cartilage degeneration and synovitis than saline-treated controls. Nociception
      were improved in the OA + meloxicam groups compared with the OA group. Moreover,
      meloxicam attenuated p38 and JNK but enhanced ERK expression in OA-affected
      cartilage. CONCLUSIONS: Intra-articular injection of meloxicam (1) attenuates the
      development of OA, (2) concomitantly reduces nociception, and (3) modulates
      chondrocyte metabolism, possibly through inhibition of cellular p38 and JNK, but
      enhances ERK expression.

PMID- 24084193
TI  - Fractionated stereotactic radiosurgery using the Novalis system for the
      management of pituitary adenomas close to the optic apparatus.
AB  - Radiosurgery has been proven to be an effective treatment for residual or
      recurrent pituitary adenomas after surgery. However, it causes severe
      complications when the optic apparatus is irradiated over the tolerance dose. In
      this study, we analyzed the feasibility of fractionated stereotactic radiosurgery
      to treat pituitary tumors close to the optic apparatus. Thirty-four patients from
      June 2006 to June 2011 with recurrent or residual pituitary adenomas close to (<3
      mm) the optic apparatus were treated with fractionated stereotactic radiosurgery.
      Three fractions with a total dose of 2100 cGy were applied to the tumors.
      Imaging, examination of vision, and estimation of hormone level were regularly
      performed before and after radiosurgery. The mean tumor volume before fractioned
      stereotactic radiosurgery was 5.06+/-3.08 cm3 (range: 0.82-12.69 cm3). After a
      mean follow up of 36.8+/-15.7 months (range: 16-72 months), tumor size was
      reduced in seven (20.6%) patients and remained the same in the other 27 (79.4%)
      patients. Vision was improved in one patient and remained stable in the rest.
      Only one patient developed transient post-treatment diplopia. This study suggests
      that fractionated stereotactic radiosurgery is safe for treating pituitary
      adenomas close to the optic apparatus. Studies with more patients and longer
      follow-up are required to draw definite conclusions.

PMID- 24084194
TI  - Tyrosine phosphorylation is essential for DSCAML1 to promote dendrite
      arborization of mouse cortical neurons.
AB  - Dendritic self-avoidance is critical for appropriate dendrite arborization. We
      herein examined the role of Down syndrome cell adhesion molecule like-1 (DSCAML1)
      in regulating dendritic self-avoidance and that of tyrosine phosphorylation in
      mediating the effects of DSCAML1. Knocking down DSCAML1 in newborn mouse cortical
      neurons compromised dendritic self-avoidance as evidenced by dendritic
      fasciculation and increased dendritic self-crossing. Introduction of a
      DSCAML1(Y1808F) mutant into the DSCAML1-knocked down neurons failed to reverse
      the abnormal dendritic arborization. These results suggest that DSCAML1 promotes
      dendritic self-avoidance in cortical neurons, and that phosphorylation at Y1808
      is essential in mediating the effects of DSCAML1. 

PMID- 24084195
TI  - Effect of lighting conditions on brain network complexity associated with
      response learning.
AB  - Several studies have reported the brain regions involved in response learning.
      However, there is discrepancy regarding the lighting conditions in the
      experimental setting (i.e. under dark or light conditions). In this regard, it
      would be relevant to know if the presence/absence of visual cues in the
      environment has any effect in the brain networks involved in a response learning
      task. Animals were trained in a water T-maze under two different lighting
      conditions (light versus dark). All subjects reached the learning criterion of
      80% correct arm choices. Quantitative cytochrome oxidase (CO) histochemistry was
      used as a metabolic brain mapping technique. Our results show that the ventral
      hippocampus and the parietal cortex are associated with the acquisition of a
      response learning task regardless of lighting conditions. In addition, when the
      same task is run in the dark, widespread recruitment of structures involving
      cortical, limbic and striatal regions was found. 

PMID- 24084196
TI  - Meta-analysis of cryoablation versus microwave ablation for small renal masses:
      is there a difference in outcome?
AB  - PURPOSE: We aimed to compare local and metastatic recurrence of small renal
      masses primarily treated by cryoablation or microwave ablation. MATERIALS AND
      METHODS: The MEDLINE, CINAHL, and PUBMED databases were searched to review the
      treatment of small renal masses with cryoablation or microwave ablation. Fifty
      one studies met the inclusion criteria. RESULTS: Fifty-one studies representing
      3950 kidney lesions were analyzed. No differences were detected in the mean
      patient age (P = 0.150) or duration of follow-up (P = 0.070). The mean tumor size
      was significantly larger in the microwave ablation group compared with the
      cryoablation group (P = 0.030). There was no difference between microwave
      ablation and cryoablation groups in terms of primary effectiveness (93.75% vs.
      91.27%, respectively; P = 0.400), cancer-specific survival (98.27% vs. 96.8%,
      respectively; P = 0.470), local tumor progression (4.07% vs. 2.53%, respectively;
      P = 0.460), or progression to metastatic disease (0.8% vs. 0%, respectively; P =
      0.120). Patient age was predictive of overall complications in the multivariate
      analysis (P = 0.020). Local tumor progression with cryoablation was predicted by
      the mean follow-up duration using univariate (P = 0.009) and multivariate
      regression (P = 0.003). Clear cell and angiomyolipoma were more frequent in the
      microwave ablation group (P < 0.0001 and P = 0.03328, respectively), and
      papillary, chromophobe, and oncocytoma were more frequent in the cryoablation
      group (P < 0.0001, P < 0.0001, and P = 0.0004, respectively). Open access was
      used more often in the microwave ablation group than in the cryoablation group
      (12.20% vs. 1.04%, respectively; P < 0.0001), and percutaneous access was used
      more frequently in the cryoablation group than in the microwave ablation group
      (88.64% vs. 37.20%, respectively; P = 0.0021). CONCLUSION: There is no difference
      in local or metastatic recurrence between cryoablation- and microwave ablation
      treated small renal masses.

PMID- 24084197
TI  - Reward-associated stimuli capture the eyes in spite of strategic attentional set.
AB  - Theories of reinforcement learning have proposed that the association of reward
      to visual stimuli may cause these objects to become fundamentally salient and
      thus attention-drawing. A number of recent studies have investigated the
      oculomotor correlates of this reward-priming effect, but there is some ambiguity
      in this literature regarding the involvement of top-down attentional set.
      Existing paradigms tend to create a situation where participants are actively
      looking for a reward-associated stimulus before subsequently showing that this
      selective bias sustains when it no longer has strategic purpose. This
      perseveration of attentional set is potentially different in nature than the
      direct impact of reward proposed by theory. Here we investigate the effect of
      reward on saccadic selection in a paradigm where strategic attentional set is
      decoupled from the effect of reward. We find that during search for a uniquely
      oriented target, the receipt of reward following selection of a target
      characterized by an irrelevant unique color causes subsequent stimuli
      characterized by this color to be preferentially selected. Importantly, this
      occurs regardless of whether the color characterizes the target or distractor.
      Other analyses demonstrate that only features associated with correct selection
      of the target prime the target representation, and that the magnitude of this
      effect can be predicted by variability in saccadic indices of feedback
      processing. These results add to a growing literature demonstrating that reward
      guides visual selection, often in spite of our strategic efforts otherwise. 

PMID- 24084198
TI  - Pyrolysis decomposition of tamarind seed for alternative fuel.
AB  - The conversion of tamarind seed into bio-oil by pyrolysis has been taken into
      consideration in the present work. The major components of the system were fixed
      bed fire-tube heating reactor, liquid condenser and collector. The crushed
      tamarind seed in particle form was pyrolyzed in an electrically heated fixed bed
      reactor. The products were liquid, char and gasses. The parameters varied were
      reactor temperature, running time, gas flow rate and feed particle size. The
      maximum liquid yield was 45 wt% at 400 degrees C for a feed size of 3200 MUm
      diameter at a gas flow rate of 6l/min with a running time of 30 min. The obtained
      pyrolysis liquid at these optimum process conditions were analyzed for physical
      and chemical properties to be used as an alternative fuel. The results show the
      potential of tamarind seed as an important source of alternative fuel and
      chemicals as well.

PMID- 24084199
TI  - Biodegradation of decabromodiphenyl ether (BDE-209) by a metal resistant strain,
      Bacillus cereus JP12.
AB  - A metal resistant bacterial strain, Bacillus cereus JP12, could use
      decabromodiphenyl ether (BDE-209) as the sole carbon and energy source for growth
      in mineral salt medium. Under the conditions of pH 6.0, 30 degrees C, 150 rpm and
      an inoculum of OD600=0.6, more than 88% of the initial BDE-209 (1mg/L) was
      degraded after 12 days. The addition of appropriate surfactants and additional
      carbon sources could enhance the biodegradation efficiency of BDE-209. The
      presence of Cu(2+) (<= 8 mg/L) and Zn(2+) (<= 15 mg/L) provided a slight
      stimulating effect on BDE-209 removal. However, BDE-209 biodegradation efficiency
      was decreased when adding higher levels of metals due to reduced substrate
      availability caused by excess metal adsorption into the cell surface. Biosorption
      of heavy metals by JP12 led to release of light metals such as K(+) and Na(+). A
      BDE-209 biodegradation pathway was proposed on the basis of metabolite
      identification.

PMID- 24084200
TI  - Study on bioadsorption and biodegradation of petroleum hydrocarbons by a
      microbial consortium.
AB  - A microbial consortium isolated from Shengli oilfield polluted sludge was capable
      of degrading naphthalene (NAP), phenanthrene (PHE), pyrene (PYR) and crude oil.
      It performed high biodegradation activity and emulsifiability for petroleum
      hydrocarbons, and was tolerant to 6.2mM Cu(2+), 2.7 mM Zn(2+) and 9.5mM Pb(2+).
      Biodegradation rates of NAP, PHE, PYR and crude oil were 53%, 21%, 32% and 44% in
      the presence of heavy metal (Cu(2+), 1.7 mM and Zn(2+), 2mM), respectively.
      Exploration on the adsorption and uptake of petroleum hydrocarbons by microbe
      suggested the stability of surface adsorption and cell uptake by live microbial
      consortium followed a decreasing order of NAP > PHE ~ PYR > crude oil. The
      adsorption by heat-killed microbial consortium was constant for PAHs, while
      decreased for crude oil. Experiments on enzymatic degradation indicated that the
      metabolic efficiency of periplasmic, cytoplasmic and extracellular enzymes
      secreted by the microbial consortium for diverse substrates was different.

PMID- 24084201
TI  - Preparation of activated carbon hollow fibers from ramie at low temperature for
      electric double-layer capacitor applications.
AB  - Activated carbon hollow fibers (ACHFs) with high surface area were prepared from
      inexpensive, renewable ramie fibers (RFs) by a single-step activation method
      under lower temperature than that of other reports. The effects of activation
      conditions on the pore structure and turbostratic structure of ACHFs were
      investigated systematically. The results show that ACHFs surface area decreased
      but micropore volume and conductivity increased as the increase of activation
      temperature and activation time. The electrochemical measurements of
      supercapacitors fabricated from these ACHFs electrodes reveal that the
      electrochemical properties improved with the enhancing of activation degree.
      However, too high activation temperature can make the ion diffusion resistance
      increase. It suggests that pore structure and conductivity are as important as
      surface area to decide the electrochemical performances of ACHFs electrode
      materials. A maximum capacity of 287 F g(-1) at 50 mA g(-1) was obtained for the
      ACHFs electrode prepared under suitable conditions.

PMID- 24084202
TI  - Synergetic decolorization of reactive blue 13 by zero-valent iron and anaerobic
      sludge.
AB  - Efficient decolorization of reactive blue 13 was achieved by a combined use of
      anaerobic sludge and zero-valent iron (ZVI), and the underlying mechanism of this
      process was elucidated, Addition of 1.0 g/L ZVI into sludge accelerated the
      decolorization, with the decoloration ratio after 1-h treatment increased by
      29.4% compared with the sum of the individual systems, indicating a synergy
      between the sludge and ZVI. Meanwhile, substantial changes in sludge morphology
      and microbial community were observed. The increased dye removal by ZVI was
      mainly attributed to: (1) a directly chemical reduction and aggregation; and (2)
      creation of a more favorable pH and anaerobic environment for microorganisms. The
      acid production by acidogens also partially offset the pH rise in ZVI corrosion
      and would alleviate ZVI deactivation. This work might offer valuable implications
      for the optimization and practical application of ZVI-anaerobic sludge processes
      for treatment of azo dyes or other recalcitrant pollutants.

PMID- 24084203
TI  - Kinetics of substrate degradation and electricity generation in anodic
      denitrification microbial fuel cell (AD-MFC).
AB  - Effect of substrate concentration on substrate degradation and electricity
      generation in anodic denitrification microbial fuel cell (AD-MFC) was
      investigated over a broad range of substrate concentrations. Substrate
      degradation rates and power generation could be promoted with increasing
      substrate concentration in a certain range, but both of them would be inhibited
      at high substrate concentrations. Maximum denitrification rate of 1.26 +/- 0.01
      kg NO(-)-N/m(3)d and maximum output voltage of 1016.75 +/- 4.74 mV could be
      achieved when initial NO3(-)-N concentration was 1999.95 +/- 2.86 mg/L. Based on
      Han-Levenspiel model, kinetics of substrate degradation and power generation in
      the AD-MFC were established. According to the kinetic model, the half-saturation
      coefficient and the critical inhibitory concentration for nitrate were more than
      200 and 4300 mg/L, respectively. The results demonstrated that AD-MFC was capable
      of treating nitrate-containing wastewater and generating electricity
      simultaneously, and tolerant to high strength nitrate-containing wastewater.

PMID- 24084204
TI  - Validation of accumulation models for inorganic suspended solids of different
      particle size in an activated sludge system.
AB  - In this study the effect of different particle sizes of inorganic suspended
      solids (ISS) on the ISS accumulation in an activated sludge system was
      investigated. The volume mean particle diameters (Dv) of ISS were 26, 73, 106,
      165, and 210 MUm. There are four fates of ISS in an activated sludge system: (1)
      suspending in the activated sludge, (2) depositing at the bottom of the reactors,
      (3) discharged from the reactors via excess sludge, and lastly (4) discharged
      from the reactors via effluent. The accumulated ISS in the bioreactor was
      unevenly distributed. Based on the accumulation proportion of ISS in bioreactor,
      an ISS accumulation model was established, from which the ISS accumulation
      concentration and the MLVSS/MLSS could be predicted. The proportion of ISS
      suspending in activated sludge was 0.22, 0.21, 0.042 and 0.031. The proportion of
      ISS depositing at the bottom of bioreactors was 0.31, 0.47, 0.75, 0.76 and 0.92.

PMID- 24084205
TI  - Membrane-based recovery of glucose from enzymatic hydrolysis of ionic liquid
      pretreated cellulose.
AB  - In this work, a membrane-based downstream process for the recovery of glucose
      from cellulose hydrolysis is described and evaluated. The cellulose is pretreated
      with the ionic liquid 1,3-dimethyl-imidazolium dimethylphosphate to reduce its
      crystallinity. After enzymatic conversion of cellulose to glucose the hydrolysate
      is filtered with an ultrafiltration membrane to remove residual particulates and
      enzymes. Nanofiltration is applied to purify the glucose from molecular
      intermediates, such as cellobiose originating from the hydrolysis reaction.
      Finally, the ionic liquid is removed from the hydrolysate via electrodialysis.
      Technically, these process steps are feasible. An economic analysis of the
      process reveals that the selling price of glucose from this production process is
      about 2.75 ?/kg which is too high as compared to the current market price.

PMID- 24084206
TI  - Effect of coagulant/flocculants on bioproducts from microalgae.
AB  - The potential of microalgae as a source of sustainable energy, nutritional
      supplements and specialized chemicals necessitates a thorough evaluation of the
      methods of harvesting microalgae with regards to the bioproduct(s) desired. This
      research assessed the effect of coagulation, flocculation, and centrifugation on
      the wet lipid extraction procedure, which fractionated microalgae into hydrolyzed
      biomass for fermentation into acetone, butanol, and ethanol, an aqueous phase as
      growth media for genetically engineered Escherichia coli, and a lipid fraction
      for the production of biodiesel. Biomass harvested by cationic starches, alum,
      and centrifugation produced 30, 19, and 22.5mg/g of dry wt. algae of total
      combined acetone, butanol, and ethanol, respectively. Higher biodiesel production
      was also observed for the cationic starches (9.6 mg/g of dry wt. algae) than alum
      (0.6 mg/g of dry wt. algae) harvested biomass. The results suggested significant
      effect of the harvesting methods on the yields of bioproducts.

PMID- 24084207
TI  - Synergistic bioleaching of chalcopyrite and bornite in the presence of
      Acidithiobacillus ferrooxidans.
AB  - Bioleaching of chalcopyrite and bornite in the presence of Acidithiobacillus
      ferrooxidans was carried out to investigate the influences between each other
      during bioleaching. Bioleaching results indicated that bornite accelerated the
      dissolution of chalcopyrite, and chalcopyrite also accelerated the dissolution of
      bornite, it could be described as a synergistic effect during bioleaching, this
      synergistic effect might be attributed to the galvanic effect between
      chalcopyrite and bornite, and to the relatively low solution potential as the
      addition of bornite. Significantly amount of elemental sulfur and jarosite formed
      on the minerals surface might be the main passivation film inhibiting the further
      dissolution, and the amount of elemental sulfur significantly increased with the
      addition of bornite. Results of electrochemical measurements indicated that the
      oxidation and reduction mechanisms of chalcopyrite and bornite were similar, the
      addition of bornite or chalcopyrite did not change the oxidative and reductive
      mechanisms, but increased the oxidation rate. 

PMID- 24084208
TI  - Expression of fatty acid desaturase genes and fatty acid accumulation in
      Chlamydomonas sp. ICE-L under salt stress.
AB  - The Antarctic ice microalgae Chlamydomonas sp. ICE-L which is highly resistant to
      salt stress holds promise in providing an alternative species for the production
      of microalgal oil. We studied the effects of the alga in confrontation with NaCl
      stress on the growth, oil yield and expression of fatty acid desaturase genes.
      The growth rate of Chlamydomonas sp. ICE-L decreased with the gradual increase in
      NaCl concentration. Interestingly, we found that the highest lipid content was
      achieved at 160/00 NaCl, reaching 23% (w/w). Meanwhile, the expression of
      Delta9ACPCiFAD increased rapidly while Delta12CiFAD, omega3CiFAD2 and Delta6CiFAD
      showed a delayed elevation in response to altered salt stress. C18:3 was the
      dominant PUFA, which account for about 75% TFA in Chlamydomonas sp. ICE-L. Under
      960/00 and 1280/00 NaCl stress, the content of C20:5 almost approached that of
      C18:3. In contrast, low salinity enhanced the dominance of C18:3 at the expense
      of C20:3 and C20:5.

PMID- 24084209
TI  - No second chances? Early critical periods in human development. Introduction.

PMID- 24084210
TI  - Impaired L-arginine uptake but not arginase contributes to endothelial
      dysfunction in rats with chronic kidney disease.
AB  - Reduced nitric oxide bioavailability contributes to increased cardiovascular
      disease risk in patients with chronic kidney disease (CKD). Arginase has been
      implicated as a potential therapeutic target to treat vascular dysfunction by
      improving substrate availability for endothelial nitric oxide synthase. The
      purpose of this study was to determine if arginase contributes to endothelial
      dysfunction in the 5/6 ablation infarction (AI) rat model of CKD. Endothelium
      dependent relaxation of aortic rings to acetylcholine was significantly impaired
      in AI animals versus sham after 8 weeks and was not improved by arginase
      inhibition (S-(2-Boronoethyl)-L-cysteine hydrochloride) alone or in combination
      with L-arginine. Additionally, scavenging of superoxide (Tempol, Tempol + L
      arginine, Tempol + L-arginine + S-(2-Boronoethyl)-L-cysteine hydrochloride) was
      not effective, suggesting that a mechanism independent of oxidative stress
      contributes to endothelium-dependent relaxation in moderate to severe CKD. Aortic
      uptake of radiolabeled L-arginine was attenuated in AI animals and was associated
      with a reduced expression of the L-arginine transporter CAT-1. These data suggest
      that arginase does not contribute to endothelial dysfunction in CKD; however,
      impaired L-arginine transport may play an important role in diminishing substrate
      availability for nitric oxide production leading to endothelial dysfunction.

PMID- 24084211
TI  - Involvement of renal sympathetic nerve overactivation in the progression of
      chronic kidney disease in rats.
AB  - Time-dependent changes in the renal sympathetic nerve activity (RSNA) in the
      progression of chronic kidney disease (CKD) have not been investigated, despite
      the fact that renal sympathetic nervous system is augmented in the condition of
      CKD. In the present study, we examined time-dependent changes in RSNA and renal
      venous norepinephrine concentrations for 12 weeks using 5 of 6 nephrectomized CKD
      rats. Both RSNA and norepinephrine concentrations were increased during the early
      phase in the progression of CKD. Urinary protein excretion and systolic blood
      pressure (SBP) were gradually increased during 12 weeks after 5 of 6 nephrectomy.
      Treatment with gamma-aminobutyric acid or the combination of prazosin and
      propranolol in the early phase (0-4 weeks) after 5 of 6 nephrectomy significantly
      attenuated the increases in urinary protein excretion and SBP in 5 of 6
      nephrectomized rats. On the other hand, the same treatment in the late phase (8
      12 weeks) after 5 of 6 nephrectomy failed to suppress the proteinuria and
      increase in SBP. Treatment with hydralazine at hypotensive dose for 12 weeks also
      failed to affect the proteinuria in 5 of 6 nephrectomized CKD rats. In
      conclusion, the augmentation of renal sympathetic nervous system in early phase
      after 5 of 6 nephrectomy is closely related to the development of partial
      ablation-induced CKD in rats.

PMID- 24084212
TI  - Lysophosphatidic acid induces shear stress-dependent contraction in mouse aortic
      strip in situ.
AB  - We previously reported that lysophosphatidic acid (LPA) regulates Ca2+ influx of
      fluid flow in stimulated endothelial cells and that LPA and shear stress showed
      increment and suppressive effects on phenylephrine-induced vasoconstriction and
      acetylcholine-induced vasodilatation, respectively. However, a vasoconstrictive
      effect of LPA alone in the presence of shear stress was not found. The present
      study examined the effect of LPA alone in the presence of shear stress on Ca2+
      responses in endothelial and smooth muscle cells and contraction in mouse aortic
      strip using real-time 2-photon laser scanning microscopy and a custom-made
      parallel-plate flow chamber. Application of micromolar LPA and high shear stress
      elicited movement of endothelial cells after Ca2+ responses. The endothelial
      cells moved along the major axis of smooth muscle cells, a direction that was
      identical to that found during vasoconstriction evoked by the application of
      phenylephrine. The frequency of Ca2+ oscillations in smooth muscle cells was
      highest according to endothelial movement. Vasoconstriction evoked by LPA and
      shear stress was significantly reduced by the application of a thromboxane A2
      receptor antagonist, a cyclooxygenase inhibitor, and a thromboxane synthase
      inhibitor. These results suggest that micromolar LPA and high shear stress elicit
      vasoconstriction that is caused by Ca2+-dependent contraction in medial smooth
      muscle cells. Thromboxane A2 may be involved in that response.

PMID- 24084213
TI  - Influence of hepatic dysfunction on the pharmacokinetics and safety of
      fimasartan.
AB  - This study was designed to assess the pharmacokinetics (PK) and safety of
      fimasartan, an angiotensin II type 1 receptor blocker, in hepatic impairment
      patients as compared with healthy subjects. An open-label, single-dose, parallel
      study was conducted in 6 healthy male volunteers and 12 subjects with hepatic
      impairment. Healthy subjects were matched with hepatic dysfunction patients on
      the basis of age, gender, and body weight. After a single 120-mg oral
      administration of fimasartan, PK parameters and safety were analyzed between the
      hepatic dysfunction groups and healthy group. Compared with the healthy subjects,
      the geometric mean ratio and 90% confidence intervals for the maximum plasma
      concentration and the mean area under the plasma concentration-time curve from 0
      to infinity (AUC)inf were 0.77 (0.24-2.47) and 1.11 (0.50-2.46), respectively,
      for the mild hepatic impairment and 6.55 (3.56-12.03) and 5.17 (4.19-6.37),
      respectively, for moderate hepatic impairment. However, there was no significant
      difference in time to peak plasma concentration (t(max)) and elimination half
      life, and there were no serious or severe adverse events in all subjects.
      Subjects with mild hepatic impairment exhibited similar bioavailability compared
      with healthy subjects, whereas subjects with moderate hepatic impairment seemed
      to exhibit a higher level of systemic exposure to fimasartan than healthy
      subjects. In addition, all subjects were tolerable with fimasartan.

PMID- 24084214
TI  - Markers of inflammation, endothelial activation, and arterial stiffness in
      hypertensive heart disease and the effects of treatment: results from the SILVHIA
      study.
AB  - We assessed the contribution of blood pressure (BP), inflammation, and
      endothelial activation to the development of structural vascular and cardiac
      changes in hypertension. Furthermore, the effects of antihypertensive therapy
      were studied. We studied 114 patients with hypertension and left ventricular
      hypertrophy and 38 matched hypertensive subjects without cardiac hypertrophy and
      38 normotensive subjects. The group with hypertension and cardiac hypertrophy
      were randomized to treatment with an angiotensin receptor blocker (irbesartan) or
      a beta-adrenergic receptor blocker (atenolol) for 48 weeks. Markers of
      inflammation (high-sensitive C-reactive protein, interleukin-6, leukocyte
      counts), vascular function (ambulatory aortic stiffness index, arterial
      compliance, and pulse pressure), and endothelial activation (E-selectin,
      intracellular adhesion molecule-1, vascular adhesion molecule-1) were assessed.
      Markers of inflammation and arterial stiffness were lowest in the normotensive
      group and highest in patients with hypertensive heart disease; endothelial
      markers were similar between groups. Inflammation was independently related to
      BP. Markers of arterial stiffness were independently related to BP and to a
      lesser extent to left ventricular mass. Antihypertensive treatment improved
      arterial compliance; inflammatory and endothelial markers remained unchanged. In
      conclusion, markers of inflammation and arterial stiffness are independently
      related to BP. Antihypertensive therapy seems to improve arterial stiffness, but
      effects on markers of inflammation and endothelial activation are small.

PMID- 24084215
TI  - Inhibition of phosphatidylinositol 3-kinase/Akt signaling attenuates hypoxia
      induced pulmonary artery remodeling and suppresses CREB depletion in arterial
      smooth muscle cells.
AB  - Hypoxia-induced pulmonary hypertension is characterized by progressive remodeling
      of the pulmonary artery (PA) system and loss of the transcription factor, cAMP
      response element binding protein (CREB) in PA smooth muscle cells (SMCs).
      Previous in vitro studies suggested that platelet-derived growth factor, a
      mitogen produced in the hypoxic arterial wall, elicits loss of CREB in medial
      SMCs via the PI3K/Akt pathway. These events trigger switching of SMCs from a
      quiescent, contractile phenotype to a proliferative, migratory, dedifferentiated,
      and synthetic phenotype, which contributes to PA thickening. Here, we
      investigated whether inhibition of PI3K or Akt could attenuate arterial
      remodeling in the lung and prevent CREB loss in PA medial SMCs in rats subjected
      to chronic hypoxia. Inhibition of either enzyme-blunted hypoxia-induced PA
      remodeling and SMC CREB depletion and diminished SMC proliferation and collagen
      deposition. Inhibition of Akt, but not PI3K, suppressed muscularization of distal
      arterioles and blunted right ventricular hypertrophy. Interestingly, mean PA
      pressure was elevated equally by hypoxia in untreated and inhibitor-treated
      groups but was normalized acutely by the Rho kinase inhibitor, Fasudil. We
      conclude that PI3K and Akt inhibitors can attenuate hypoxia-induced PA remodeling
      and SMC CREB depletion but fail to block the development of pulmonary
      hypertension because of their inability to repress Rho kinase-mediated
      vasoconstriction.

PMID- 24084217
TI  - Effects of endothelin-1 chronic stimulation on electrical restitution, beat-to
      beat variability of repolarization, and ventricular arrhythmogenesis.
AB  - Chronically elevated levels of endothelin-1 (ET-1) have been detected in several
      cardiovascular diseases. In this study, we investigated the chronic effects of ET
      1 on the electrophysiological characteristics expected to influence the genesis
      and maintenance of ventricular arrhythmia (VA). Rabbits were randomized to ET-1
      (ET-1 group) or 0.9% saline (control group) for 2 weeks. The S1-S2 protocol and
      S1-S1 dynamic pacing were performed to assess the action potential duration
      restitution (APDR) and to induce APD alternans or VA in 4 sites of Langendorff
      perfused rabbit hearts. The beat-to-beat variability of repolarization was
      quantified as short-term variability and long-term variability. Compared with the
      control group, chronic ET-1 administration significantly prolonged QT intervals,
      APD at 90% repolarization (APD90), and effective refractory period (ERP),
      steepened the maximum slopes of the APDR curve, decreased the ERP/APD90 ratio,
      and increased the spatial dispersions of APD90, ERP, and maximum slopes (P < 0.05
      for all). Moreover, chronic ET-1 administration markedly increased the short-term
      variability and long-term variability (P < 0.01 for all). APD alternans occurred
      in both groups, but the threshold of APD alternans was decreased at all sites in
      the ET-1 group (P < 0.01 for all). We also observed that chronic ET-1 stimulation
      significantly increased the incidence and duration of the VA episodes. These
      results suggest that chronic stimulation with ET-1 facilitated VA by steepening
      the APDR curve and increasing the spatial dispersion of APDR and beat-to-beat
      variability of repolarization.

PMID- 24084216
TI  - Atrophic cardiomyocyte signaling in hypertensive heart disease.
AB  - Cardinal pathological features of hypertensive heart disease (HHD) include not
      only hypertrophied cardiomyocytes and foci of scattered microscopic scarring, a
      footprint of prior necrosis, but also small myocytes ensnared by fibrillar
      collagen where disuse atrophy with protein degradation would be predicted.
      Whether atrophic signaling is concordant with the appearance of HHD and involves
      oxidative and endoplasmic reticulum (ER) stress remains unexplored. Herein, we
      examine these possibilities focusing on the left ventricle and cardiomyocytes
      harvested from hypertensive rats receiving 4 weeks aldosterone/salt treatment
      (ALDOST) alone or together with ZnSO4, a nonvasoactive antioxidant, with the
      potential to attenuate atrophy and optimize hypertrophy. Compared with untreated
      age-/sex-/strain-matched controls, ALDOST was accompanied by (1) left ventricle
      hypertrophy with preserved systolic function; (2) concordant cardiomyocyte
      atrophy (<1000 MUm2) found at sites bordering on fibrosis where they were
      reexpressing beta-myosin heavy chain; and (3) upregulation of ubiquitin ligases,
      muscle RING-finger protein-1 and atrogin-1, and elevated 8-isoprostane and
      unfolded protein ER response with messenger RNA upregulation of stress markers.
      ZnSO4 cotreatment reduced lipid peroxidation, fibrosis, and the number of
      atrophic myocytes, together with a further increase in cell area and width of
      atrophied and hypertrophied myocytes, and improved systolic function but did not
      attenuate elevated blood pressure. We conclude that atrophic signaling,
      concordant with hypertrophy, occurs in the presence of a reparative fibrosis and
      induction of oxidative and ER stress at sites of scarring where myocytes are
      atrophied. ZnSO4 cotreatment in HHD with ALDOST attenuates the number of atrophic
      myocytes, optimizes size of atrophied and hypertrophied myocytes, and improves
      systolic function.

PMID- 24084218
TI  - Cerebrovascular dysfunction and blood-brain barrier permeability induced by
      oxidized LDL are prevented by apocynin and magnesium sulfate in female rats.
AB  - Oxidized low-density lipoprotein (oxLDL) is elevated during several neurologic
      conditions that involve cerebral edema formation, including severe preeclampsia
      and eclampsia; however, our understanding of its effect on the cerebral
      vasculature is limited. We hypothesized that oxLDL induced blood-brain barrier
      (BBB) disruption and changes in cerebrovascular reactivity occur through NADPH
      oxidase-derived superoxide. We also investigated the effect of MgSO4 on oxLDL
      induced changes in the cerebral vasculature as this is commonly used in
      preventing cerebral edema formation. Posterior cerebral arteries from female rats
      were perfused with 5 ug/mL oxLDL in rat serum with or without 50 uM apocynin or
      16 mM MgSO4 and BBB permeability and vascular reactivity were compared. oxLDL
      increased BBB permeability and decreased myogenic tone that were prevented by
      apocynin. oxLDL increased constriction to the nitric oxide synthase inhibitor
      nitro-L-arginine that was unaffected by apocynin. oxLDL enhanced dilation to the
      NO donor sodium nitroprusside that was prevented by apocynin. MgSO4 prevented
      oxLDL-induced BBB permeability without affecting oxLDL-induced changes in
      myogenic tone. Thus, oxLDL seems to cause BBB disruption and vascular tone
      dysregulation through NADPH oxidase-derived superoxide. These results highlight
      oxLDL and NADPH oxidase as potentially important therapeutic targets in
      neurologic conditions that involve elevated oxLDL.

PMID- 24084219
TI  - Subcutaneous to intravenous prostacyclin analog transition in pulmonary
      hypertension.
AB  - INTRODUCTION: Prostacyclin analogs are Food and Drug Administration-approved
      therapies for the treatment of pulmonary arterial hypertension and can be
      administered by inhalational, intravenous (IV), or subcutaneous (SQ) routes.
      Because there are limited data to guide the transition between SQ to IV
      prostacyclin analogs, we describe our experience. METHODS: We performed a
      retrospective review of patients with pulmonary hypertension diagnosed by right
      heart catheterization, who underwent transition from SQ to IV prostacyclin
      analogs. RESULTS: We included 7 patients with pulmonary arterial hypertension and
      2 with chronic thromboembolic pulmonary hypertension in this retrospective study.
      Median (interquartile range) age was 54 (39-63) years, and 67% were women. The
      reasons for the SQ to IV switch were site pain (n = 6, 67%), major surgery (n =
      2, 22%), and septic shock (n = 1, 11%). SQ treprostinil was converted to IV
      treprostinil (n = 5, 56%) or IV epoprostenol (n = 4, 44%). When SQ treprostinil
      was converted to IV treprostinil, the initial mean (range) dose decreased from
      84.9 (36.5-167) to 70.8 (24-114) ng.kg-1.min-1. When SQ treprostinil was
      converted to IV epoprostenol, the dose decreased from 24.5 (17.5-30) to 13.3 (9
      20) ng.kg-1.min-1. The patient transitioned from SQ to IV treprostinil in the
      context of septic shock died a month after hospitalization. No deteriorations
      were observed in the remaining patients during the first year. CONCLUSIONS: Under
      careful monitoring, SQ treprostinil was transitioned to IV treprostinil or
      epoprostenol without complications. Dosing downadjustment was needed in some
      patients who were switched over from SQ to IV prostacyclin analogs.

PMID- 24084220
TI  - Toll-like receptor 4 inhibitor TAK-242 treatment does not influence perfusion
      recovery in tissue ischemia.
AB  - Toll-like receptors (TLRs) are important in innate immune responses, which are
      crucial in collateral artery formation (arteriogenesis). TLR4-/- mice undergoing
      hind limb ischemia show decreased perfusion recovery accompanied by an impaired
      infiltration of inflammatory cells. TLR antagonists are currently developed and
      tested with the objective to inhibit acute exacerbation of organ damaging immune
      responses. However, systemic inhibition of innate immune responses may negatively
      influence arteriogenesis. In this study, we evaluated if TLR4 inhibition by a
      potent TLR4 inhibitor (TAK-242) would negatively influence perfusion recovery in
      a mouse model for arteriogenesis. Whole blood from human and mouse origin was
      stimulated with the TLR4 ligand lipopolysaccharide following TAK-242 incubation.
      After stimulation, cellular TLR4 activation was measured using fluorescence
      activated cell sorting and tumor necrosis factor alpha release was measured using
      enzyme-linked immunosorbent assay. Next, the effect of TAK-242 was tested in a
      mouse model for arteriogenesis on perfusion recovery. TLR4 responses measured by
      tumor necrosis factor alpha levels were inhibited by TAK-242 in human and mouse
      blood after long-term stimulation. TAK-242 attenuated TLR4 responses in vivo but
      did not inhibit perfusion recovery in mice. In conclusion, TAK-242 does not
      negatively influence perfusion recovery following hind limb ischemia despite its
      TLR4 inhibiting properties.

PMID- 24084221
TI  - Potentiated adrenomedullin-induced vasorelaxation during hypoxia in organ
      cultured porcine coronary arteries.
AB  - This study describes the effect of variable oxygen supply on relaxing responses
      induced by alpha-calcitonin gene-related peptide (CGRP) and adrenomedullin (AM)
      on isolated pig coronary arteries in vitro. Organ culture during normoxia (21% of
      O2) and hypoxia (5% of O2) induced a significant leftward shift of the AM
      concentration-response curves compared with fresh vessels altering the pEC50
      values from 6.9 +/- 0.04 to 8.0 +/- 0.04, whereas the potency (pEC50) of
      alphaCGRP was attenuated from 8.8 +/- 0.04 to 7.6 +/- 0.04. AM22-52 exerted
      significant antagonistic effect on AM-induced vasorelaxation in hypoxic and
      normoxic conditions (apparent pK(B) = 6.8-7.2), whereas no antagonistic effect
      was observed in fresh and hyperoxic (95%) organ cultured vessels. The
      antagonistic effect exerted by alphaCGRP8-37 (10-6.5-10-5.5 M) on alphaCGRP
      induced vasodilatation in fresh vessels (derived from Schild plot pA2 = 7.4 +/-
      0.1) was unaltered during organ culture. The antagonistic effect exerted by
      alphaCGRP8-37 (10-6 M) on AM-induced vasorelaxation in fresh vessels (apparent
      pK(B) = 7.4 +/- 0.1) was absent during hypoxic organ culture. The receptor
      activity-modifying proteins 1 (RAMP1)/calcitonin-like receptor (CLR) messenger
      RNA ratio was reduced and RAMP2/CLR messenger RNA ratio was increased during
      hypoxic and normoxic organ culture compared with fresh vessels. Hypoxic organ
      culture for 24-72 hours potentiated the AM-induced vasorelaxation through an AM22
      52-sensitive receptor but attenuated the vasorelaxant effect of CGRP through the
      CGRP receptors. This could possibly be explained by relatively decreased levels
      of RAMP1, thus favoring RAMP2 + CLR complex (=AM receptor) formation during
      hypoxic organ culture.

PMID- 24084222
TI  - Dronedarone versus amiodarone in preventing premature ventricular contractions in
      an in vitro model of "border zone".
AB  - OBJECTIVE: To compare the acute ability of amiodarone and dronedarone (a
      noniodinated benzofuran derivative with a pharmacologic profile similar to
      amiodarone) to prevent premature ventricular contractions (PVCs) occurrence.
      METHODS: We used an in vitro model of rabbit right ventricle mimicking the
      "border zone" existing between normal and ischemic/reperfused regions to test
      acute electrophysiological effects of dronedarone and amiodarone both at 1 and 10
      MUmol/L. RESULTS: Similar to amiodarone, dronedarone affected action potential
      parameters with multichannel blocking properties. Dronedarone at both
      concentrations was equivalent to amiodarone regarding PVCs occurrence, except
      regarding extrasystoles occurrence during the reperfusion period (dronedarone, 10
      MUmol/L, was superior to amiodarone with extrasystoles incidence at 33% and 50%,
      respectively vs. 92% in controls, P < 0.05). Both dronedarone and amiodarone
      systematically induced conduction blocks during simulated ischemia (in 100% of
      preparations vs. 42% in controls, P < 0.05) and a marked decrease of Vmax (to 24
      and 23 V/s at 10 minutes of ischemia with 1 and 10 MUmol/L dronedarone versus 65
      V/s in controls, P < 0.05), thus indicating class 1 antiarrhythmic effects. Both
      dronedarone and amiodarone at 10 MUmol/L induced an increase of APD90 dispersion
      between normal and ischemic regions, without pro-arrhythmic effects. CONCLUSIONS:
      Dronedarone and amiodarone have very similar electrophysiological effects in this
      in vitro model of border zone and were both efficient in preventing PVCs
      occurrence particularly through a class 1 antiarrhythmic effect.

PMID- 24084223
TI  - The third-generation Beta-blocker: have we found the elusive, effective
      antioxidant?

PMID- 24084224
TI  - Electrophysiological and hemodynamic effects of vernakalant and flecainide during
      cardiac resynchronization in dyssynchronous canine hearts.
AB  - INTRODUCTION: Patients with heart failure and left bundle branch block (LBBB) are
      frequently treated with biventricular pacing (BiVP). Approximately one-third of
      them suffer from atrial fibrillation. Pharmacological conversion of atrial
      fibrillation is performed with drugs that slow ventricular conduction, but the
      effects of these drugs on the benefit of BiVP are poorly understood. METHODS:
      Experiments were performed in dogs with chronic LBBB, investigating the effects
      of Vernakalant and Flecainide (n = 6 each) on hemodynamics and electrophysiology
      during epicardial (EPI) and endocardial BiVP. The degree of dyssynchrony and
      conduction slowing was quantified using QRS width and EPI electrical mapping.
      RESULTS: Compared with LBBB, EPI and endocardial BiVP reduced QRS duration by 7%
      +/- 9% (P < 0.05 compared with LBBB) and 20% +/- 13% (P < 0.05 compared with
      LBBB, P < 0.05 between modes), respectively. During BiVP, the administration of
      Vernakalant and Flecainide increased QRS duration by 20% +/- 14% (P < 0.05
      compared with predrug BiVP) and 34% +/- 10% (P < 0.05 compared with predrug BiVP,
      P < 0.05 between drugs). left ventricular (LV) dP/dtmax decreased by 16% +/- 8%
      (P < 0.05 compared with predrug BiVP) during Vernakalant and by 14% +/- 15% (P <
      0.05 compared with predrug BiVP) during Flecainide. The drugs did not affect the
      relative changes in QRS width and LV dP/dtmax induced by BiVP. CONCLUSIONS:
      Vernakalant and Flecainide decrease contractility, slow myocardial conduction
      velocity, and increase activation time. The electrical and hemodynamic benefits
      of BiVP are not altered by the drugs.

PMID- 24084225
TI  - Atrial-selective antiarrhythmic activity by vernakalant fact or fiction?

PMID- 24084227
TI  - Effect of gender on the quadriceps-to-hamstrings coactivation ratio during
      different exercises.
AB  - CONTEXT: Coactivation ratio of quadriceps to hamstring muscles (Q:H) and medial
      to lateral knee muscles (M:L) contributes to the dynamic stability of the knee
      joint during movement patterns recommended during rehabilitation and important
      for daily function. OBJECTIVE: To compare the quadriceps-to-hamstring and medial
      to-lateral knee muscles' coactivation ratios between men and women during the
      following closed kinetic chain exercises performed on a balance board: forward
      lunge, side lunge, single-leg stance, and single-leg squat. DESIGN: Cross
      sectional. PARTICIPANTS: 20 healthy subjects (10 female and 10 male). MAIN
      OUTCOME MEASURES: Surface electromyography was used to measure the activation
      level of quadriceps (vastus lateralis and medialis) and hamstrings (biceps
      femoris and medial hamstrings) during forward- and side-lunge, single-leg-stance,
      and single-leg-squat exercises. Subjects were instructed during each exercise to
      move into the test position and to hold that position for 15 s. EMG was recorded
      during the 15-s isometric period where subjects tried to maintain a "set"
      position while the foot was on a balance board. Analysis of variance was used for
      statistical analysis. RESULTS: There was a significant exercise-by-gender
      interaction for Q:H ratio (F3,48 = 6.63, P = .001), but the exercise-by-gender
      interaction for M:L ratio was not significant (F3,48 = 1.67, P = .18). Women
      showed larger Q:H ratio in side-lunge exercises than men (P = .002). Both genders
      showed larger M:L and lower Q:H ratio in a single-leg-stance exercise than in the
      other exercises. CONCLUSIONS: The results indicate that the forward- and side
      lunge and single-leg-squat exercises should not be recommended as exercise where
      a balanced coactivation between quadriceps and hamstring muscles is warranted.
      Single-leg-stance exercise could be used when seeking an exercise where the ratio
      is balanced for both women and men.

PMID- 24084228
TI  - Examining determinants of early and late age at onset in panic disorder: an
      admixture analysis.
AB  - Past research demonstrated that age at onset might account for different clinical
      and etiological characteristics in panic disorder (PD). However, prior research
      relied on arbitrary choices of age cut-offs. Using a data-driven validated
      method, this study aimed to examine differences between early and late onset PD
      in various determinants. Admixture analysis was used to determine the best
      fitting model of age at onset distribution in PD. Data was collected from 511
      individuals (ages 18-65) with PD diagnoses, who participated in the Netherlands
      Study of Depression and Anxiety (NESDA). DSM-IV comorbidities and various
      measures of childhood adversities, suicidal behavior, anxiety and depressive
      symptoms were assessed. The best fitting cut-off score between early and late age
      at onset groups was 27 years (early age at onset <= 27 years). Univariate tests
      showed that participants with early onset PD were younger and more likely to be
      female. Early onset PD was associated with agoraphobia, higher frequency of
      childhood trauma and life events, and higher rates of suicide attempts as
      compared to late onset PD. Multivariate logistic regression analysis demonstrated
      that only current age, childhood trauma and agoraphobia remained significantly
      associated with early onset PD. Findings suggest that 27 years marks two onset
      groups in PD, which are slightly distinct. Early onset PD is independently
      associated with exposure to childhood trauma and increased avoidance. This
      highlights the importance of subtyping age of onset in PD. Clinical implications
      are further discussed.

PMID- 24084229
TI  - A systematic review of endoprosthetic replacement for non-tumour indications
      around the knee joint.
AB  - BACKGROUND: Endoprosthetic replacement (EPR) for limb salvage is an established
      treatment modality for orthopaedic malignancies around the knee. Increasingly,
      they are being used for non-tumour indications such as fractures, bone loss
      associated with aseptic loosening, septic loosening and ligament insufficiencies.
      METHODS: We reviewed the evolution and biomechanics of knee EPRs. MEDLINE was
      searched using the PubMed interface to identify relevant studies pertaining to
      the use of knee EPRs in non-tumour conditions. Failures, mortality and knee
      scores were the main outcome measures. Subgroup analysis in the non-tumour
      conditions was also performed. RESULTS: There were nine studies with an average
      follow-up of 3.3years (Range 1-5years) describing 241 EPRs used in non-tumour
      conditions. Re-operation for any reason occurred in 17% (41/241) of cases. The
      most common complication was infection (15%) followed by aseptic loosening (5%)
      and periprosthetic fractures (5%). The mortality rate averaged 22%. Infected knee
      arthroplasties were less likely to have a successful outcome when salvaged with
      an EPR with failure rates up to 33%. CONCLUSIONS: Endoprosthetic replacement is a
      limb salvage option when other surgical options are unfeasible, especially in low
      demand elderly patients with limited life expectancy. They have low rates of
      failure in the medium term. LEVEL OF EVIDENCE: Level 1.

PMID- 24084230
TI  - Effects of deep-horn AI on fertilization and embryo production in superovulated
      cows and heifers.
AB  - The primary objective of this study was to determine the effect of site of semen
      deposition on fertilization rate and embryo quality in superovulated cows. The
      hypothesis was that deposition of semen into the uterine horns would increase the
      fertilization rate compared with deposition of semen into the uterine body. The
      secondary objective was to evaluate the effect of uterine environment on
      fertilization rate and embryo quality. It was hypothesized that subclinical
      endometritis at the onset of superstimulation would decrease the fertilization
      rates and embryo quality. In experiment 1, 17 superovulated heifers were randomly
      assigned to receive artificial insemination (AI) into the uterine body or uterine
      horns. The total number of fertilized structures and fertilization rate from
      superovulated heifers was increased (P = 0.04 and P = 0.02, respectively) when
      semen was deposited into the uterine horns compared with the uterine body. Other
      embryo characteristics did not differ based on the site of semen deposition. In
      experiment 2, 14 lactating dairy cows were superovulated twice and were randomly
      assigned to receive AI into the uterine body or deep into the uterine horns using
      a crossover design. Neither fertilization rate nor any other embryo
      characteristics were improved when semen was placed deep into the uterine horns
      compared with the uterine body. In experiment 3, 72 superovulated lactating dairy
      cows were randomly assigned to receive AI into the uterine body or uterine horns.
      Before initiation of superstimulatory treatments, an endometrial cytology sample
      was collected from each cow. Ova/embryos were collected by a nonsurgical
      technique at 70 +/- 3 days in milk. Similar to experiment 2, neither
      fertilization rate nor any other embryo characteristics differed based on the
      site of semen deposition in experiment 3. The percentage of cows with subclinical
      endometritis did not differ between treatments. Interestingly, there was a
      tendency (P = 0.09) for a reduction in embryo recovery rate and a reduction (P =
      0.01) in the fertilization rate for cows with subclinical endometritis. In
      conclusion, deposition of semen into the uterine horns rather than into the
      uterine body did not improve the fertilization rate or embryo quality in
      superovulated cows. Subclinical endometritis decreased the fertilization rate in
      superovulated cows. 

PMID- 24084231
TI  - Coculturing cumulus oocyte complexes with denuded oocytes alters zona pellucida
      ultrastructure in in vitro matured bovine oocytes.
AB  - Oocyte quality is a key factor affecting success of in vitro embryo production in
      cattle. Improving the microenvironment of oocytes during in vitro maturation
      (IVM) can increase developmental rate and embryo quality. Therefore, the
      objective was to determine whether denuded oocytes (DO) affect embryo development
      and ultrastructure of the zona pellucida (ZP) in in vitro matured bovine oocytes.
      Intact immature cumulus-oocytes complexes (COC) obtained from a local abattoir or
      by ovum pick-up (OPU) were cocultured with and without abattoir-obtained DO at a
      COC:DO ratio of 1:5. After IVM, DO were removed and intact DO were either
      fertilized or observed by scanning electron microscopy. Blastocyst quality was
      evaluated using a TUNEL assay. The ZP pore size decreased after IVM in COC + DO
      coculture, regardless of their origin (OPU, 310.5 +/- 92.5 vs. 428.9 +/- 148.5
      nm; abattoir, 317.5 +/- 68.5 vs. 358.9 +/- 128.5 nm; P < 0.05; mean values +/-
      standard deviation). Moreover, the number of ZP pores in OPU COC + DO and COC +
      DO was greater than those in OPU COC and COC (control) groups (56 +/- 4 and 55 +/
      7 vs. 50 +/- 6 and 42 +/- 4; P < 0.05). The rate of blastocyst development in
      COC + DO and OPU COC + DO groups was greater those in control and OPU COC groups
      (36.6% and 55.5% vs. 28.1% and 40.0%; P < 0.05). Moreover, the total cell numbers
      of blastocysts in COC + DO group exceeded that of control (132.91 +/- 30.90 vs.
      115.44 +/- 24.95; P < 0.05), with no significant between OPU COC + DO and OPU COC
      groups (139.31 +/- 42.51 vs. 137.00 +/- 61.34). In conclusion, in vitro embryo
      development competence and quality improved when oocytes were cocultured with DO.
      Furthermore, there more, but smaller, ZP pores. 

PMID- 24084232
TI  - Active immunization against GnRH reduces the synthesis of GnRH in male rats.
AB  - We sought to determine the effects of active anti-GnRH immunization on GnRH
      synthesis in the hypothalamus. Adult male rats (n = 36) were randomly and equally
      allocated into three groups: Control (no treatment), surgically castrated, or
      immunized against 50 MUg D-Lys6-GnRH-tandem-dimer peptide conjugated to ovalbumin
      in Specol adjuvant at 12 week of age (with a booster 8 week later). Blood samples
      (for antibody titers and hormone concentrations) were collected at 2-week
      intervals until rats were killed (20 week). Compared with intact controls,
      immunocastration reduced (P < 0.05) serum concentrations of testosterone, LH, and
      FSH, and GnRH content in the median eminence, reduced the weight of the hypohysis
      (P < 0.01), and induced testicular atrophy (suppression of spermatogenesis).
      Furthermore, mRNA expression of GnRH in the hypothalamus, GnRH receptor, LH-beta
      and FSH-beta in the pituitary, LH receptor and FSH receptor in the testes, and
      genes in sex steroid feedback loops (androgen receptor [AR], kisspeptin encoded
      gene (Kiss-1), and kisspeptin receptor (GPR54) in the hypothalamus were decreased
      in immunocastrated rats compared with intact controls (P < 0.05). Similarly,
      surgical castration reduced GnRH in the median eminence as well as mRNA
      expression of GnRH, AR, Kiss-1, and GPR54 in the hypothalamus (P < 0.05). We
      concluded that anti-GnRH immunization in adult rats reduced synthesis of
      hypothalamic GnRH by decreasing androgen-AR-Kisspeptin-GPR54 signaling pathways,
      and caused dysfunction of the pituitary-testicular axis, thereby suppressing
      spermatogenesis, resulting in testicular atrophy. 

PMID- 24084233
TI  - Role of the AP-1 transcription factor FOSL1 in endothelial cells adhesion and
      migration.
AB  - Vasculogenesis and angiogenesis, the fundamental processes by which new blood
      vessels are formed, involve the proliferation, migration, and remodeling of
      endothelial cells. Dynamic adhesion of endothelial cells to extracellular matrix
      plays a fundamental role in all these events. Key regulators of endothelial cells
      adhesion and migration are the alphavbeta3 and uPA-uPAR complexes. The
      alphavbeta3 integrin heterodimer is the receptor for extracellular matrix
      components such as vitronectin and is overexpressed on the cell surface of
      angiogenic endothelial cells, but not quiescent cells lining normal vessels. The
      uPA-uPAR complex contributes to extracellular matrix remodeling by mediating
      proteolytic activity at the leading edge of migrating cells. We recently reported
      that the FOSL1 transcription factor of the AP-1 family plays a pivotal role in
      the regulation of the level of the alphavbeta3 and uPA-uPAR complexes on the
      surface of endothelial cells. In this commentary, we review the current knowledge
      of alphav and beta3 transcriptional regulation in endothelial cells and discuss
      the role of FOSL1 in angiogenesis. 

PMID- 24084234
TI  - Sequence heterogeneity of the ORF3 gene of porcine epidemic diarrhea viruses
      field samples in Fujian, China, 2010-2012.
AB  - Twenty-seven field samples that showed positive in PEDV detection were collected
      from different farms of Fujian province from 2010 to 2012. Their heterogeneity
      was investigated by analysis of the ORF3 gene because of its potential function
      as a representation of virulence. According to the results, six Fujian strains in
      Group 1 showed a different genotype with unique point mutations, which might be
      used in differentiation between PEDV groups and brought potential antigenic
      variation. P55 and five reference strains in Group 2 had a long length deletion,
      showing another genotype and might be involved in the variation of virulence.
      Phylogenetic analysis revealed that the collected Fujian strains were very
      distant from the vaccine development strain CV777, which might be the reason why
      the vaccine was inefficient to control the disease. The results can help to
      reconsider the strategy of PEDV vaccine management and prevent outbreaks of PEDV
      induced diarrhea more efficiently. 

PMID- 24084237
TI  - In-silico analysis for RNA-interference mechanism of alpha-synuclein to treat
      Parkinson's disease.
AB  - Parkinson's Disease (PD) causing mutations in alpha-synuclein gene are ALA30PRO,
      GLU46LYS and ALA53THR. The conformational changes in proteins with respect to all
      the three mutations were analysed. These were used to predict the structures of
      Short Interfering RNA (siRNA) antisense strand and siRNA region. The siRNA binds
      with the argonaute protein forming RNA Induced Silencing Complex (RISC). Then,
      siRNA antisense-strand was attached to RISC. The structure of dicer (RNase-III
      enzyme) cleaves double-stranded RNA (dsRNA) into two siRNA-strands. Incorporation
      of single siRNA-strand into RISC guides to pair with the complementary alpha
      synuclein target-messenger RNA (mRNA) thereby enabling it to cleave the target. 

PMID- 24084235
TI  - Vaccines in development against West Nile virus.
AB  - West Nile encephalitis emerged in 1999 in the United States, then rapidly spread
      through the North American continent causing severe disease in human and horses.
      Since then, outbreaks appeared in Europe, and in 2012, the United States
      experienced a new severe outbreak reporting a total of 5,387 cases of West Nile
      virus (WNV) disease in humans, including 243 deaths. So far, no human vaccine is
      available to control new WNV outbreaks and to avoid worldwide spreading. In this
      review, we discuss the state-of-the-art of West Nile vaccine development and the
      potential of a novel safe and effective approach based on recombinant live
      attenuated measles virus (MV) vaccine. MV vaccine is a live attenuated negative
      stranded RNA virus proven as one of the safest, most stable and effective human
      vaccines. We previously described a vector derived from the Schwarz MV vaccine
      strain that stably expresses antigens from emerging arboviruses, such as dengue,
      West Nile or chikungunya viruses, and is strongly immunogenic in animal models,
      even in the presence of MV pre-existing immunity. A single administration of a
      recombinant MV vaccine expressing the secreted form of WNV envelope glycoprotein
      elicited protective immunity in mice and non-human primates as early as two weeks
      after immunization, indicating its potential as a human vaccine. 

PMID- 24084236
TI  - Viruses challenge selectivity barrier of nuclear pores.
AB  - Exchange between the nucleus and the cytoplasm occurs through nuclear pore
      complexes (NPCs) embedded in the double membrane of the nuclear envelope. NPC
      permeability barrier restricts the entry of inert molecules larger than 5 nm in
      diameter but allows facilitated entry of selected cargos, whose size can reach up
      to 39 nm. The translocation of large molecules is facilitated by nuclear
      transport receptors (NTRs) that have affinity to proteins of NPC permeability
      barrier. Viruses that enter the nucleus replicate evolved strategies to overcome
      this barrier. In this review, we will discuss the functional principles of NPC
      barrier and nuclear transport machinery, as well as the various strategies
      viruses use to cross the selective barrier of NPCs. 

PMID- 24084238
TI  - Challenges in the miRNA research.
AB  - While it is known that the human genes are regulated by microRNAs (miRNAs),
      recent links with cancer and other diseases have widely caught interest. With
      several bioinformatics platforms and approaches on rise that has led to discovery
      of human miRNAs, validation and need for understanding miRNAs from their
      progenitor messenger RNAs (mRNAs) have arisen. Furthermore, the miRNAs are known
      to have synergism involving regulation of their condition-specific target genes
      (mRNAs). In this review, we provide a bioinformatics approach of the miRNAs and
      their challenges with respect to annotation. With introduction of sequence
      specific miRNA signatures recently found, we discussed myriad of dimensions where
      miRNAs are being associated with several putative functional and evolutionary
      events, and then we asked a question how far and relevant is the association of
      miRNAs with mRNAs? 

PMID- 24084239
TI  - Genetic algorithm solution for partial digest problem.
AB  - One of the fundamental problems in computational biology is the construction of
      physical maps of chromosomes from the hybridisation experiments between unique
      probes and clones of chromosome fragments. Before introducing the shotgun
      sequencing method, Partial Digest Problem (PDP) was an intractable problem used
      to construct the physical maps of DNA sequence in molecular biology. In this
      paper, we develop a novel Genetic Algorithm (GA) for solving the PDP. This
      algorithm is implemented and compared with well-known existing algorithms on
      different types of random and real instances data, and the obtained results show
      the efficiency of our algorithm. Also, our GA is adapted to handle the erroneous
      data and their efficiency is presented for the large instances of this problem. 

PMID- 24084240
TI  - Putative drug targets in Rhizopus oryzae: in-silico insight.
AB  - Opportunistic fungal infections, such as zygomycosis, often associated with
      excessive morbidity and mortality, are increasingly becoming a source of concern
      worldwide. In the reported investigation, genome analysis of a major
      opportunistic fungus Rhizopus oryzae was undertaken to identify gene or protein
      sequences that may serve as targets for therapeutic interventions. Using database
      of essential genes six proteins were identified. These proteins are implicated in
      metabolic/cellular pathways, which are more likely to be crucial for target
      organism's viability. Their utility as potential drug targets is discussed. 

PMID- 24084241
TI  - Evolutionary history and phylogenetic relationship between Auxis thazard and
      Auxis rochei inferred from COI sequences of mtDNA.
AB  - Tunas of the genus Auxis are cosmopolitan species and the smallest members of the
      tribe Thunnini, the true tunas. In the present study, COI sequences of mtDNA were
      employed to examine the evolutionary history and phylogenetic relationship
      between A. thazard and A. rochei. A total of 29 COI sequences were retrieved from
      NCBI. Historic demographic analyses of sequence data showed that A. thazard has
      undergone sudden population expansion in the past while population size of A.
      rochei has been remain constant for long period. Non-significant value of
      Tajimas's D (P = 0.22400) and Fu's FS (P = 0.21400) test fail to reject the null
      hypothesis of neutral evolution for A. rochei. Phylogenetic analyses of
      nucleotide sequences demonstrated separate clusters for both species and are
      strongly supported by 98% bootstrap value. The results of the present study
      suggest the recent founding of A. thazard in world ocean while A. rochei
      represents the ancestral species. 

PMID- 24084242
TI  - Novel hybrid genetic algorithm for progressive multiple sequence alignment.
AB  - The family of evolutionary or genetic algorithms is used in various fields of
      bioinformatics. Genetic algorithms (GAs) can be used for simultaneous comparison
      of a large pool of DNA or protein sequences. This article explains how the GA is
      used in combination with other methods like the progressive multiple sequence
      alignment strategy to get an optimal multiple sequence alignment (MSA). Optimal
      MSA get much importance in the field of bioinformatics and some other related
      disciplines. Evolutionary algorithms evolve and improve their performance. In
      this optimisation, the initial pair-wise alignment is achieved through a
      progressive method and then a good objective function is used to select and align
      more alignments and profiles. Child and subpopulation initialisation is based
      upon changes in the probability of similarity or the distance matrix of the
      alignment population. In this genetic algorithm, optimisation of mutation,
      crossover and migration in the population of candidate solution reflect events of
      natural organic evolution. 

PMID- 24084243
TI  - A method for culturing embryonic C. elegans cells.
AB  - C. elegans is a powerful model system, in which genetic and molecular techniques
      are easily applicable. Until recently though, techniques that require direct
      access to cells and isolation of specific cell types, could not be applied in C.
      elegans. This limitation was due to the fact that tissues are confined within a
      pressurized cuticle which is not easily digested by treatment with enzymes and/or
      detergents. Based on early pioneer work by Laird Bloom, Christensen and
      colleagues developed a robust method for culturing C. elegans embryonic cells in
      large scale. Eggs are isolated from gravid adults by treatment with bleach/NaOH
      and subsequently treated with chitinase to remove the eggshells. Embryonic cells
      are then dissociated by manual pipetting and plated onto substrate-covered glass
      in serum-enriched media. Within 24 hr of isolation cells begin to differentiate
      by changing morphology and by expressing cell specific markers. C. elegans cells
      cultured using this method survive for up 2 weeks in vitro and have been used for
      electrophysiological, immunochemical, and imaging analyses as well as they have
      been sorted and used for microarray profiling.

PMID- 24084245
TI  - Emergence of carbapenem-resistant Acinetobacter baumannii harboring the OXA-23
      carbapenemase in intensive care units of Egyptian hospitals.
AB  - BACKGROUND: Healthcare-associated infections are a worldwide threat to
      hospitalized patients, especially those in intensive care units. The prevalence
      of these infections in Egypt, and their antimicrobial resistance patterns and
      mechanisms, were investigated in this study. METHODS: A total of 547 cases of
      healthcare-associated infections were investigated. Causative agents were
      identified and antimicrobial susceptibility determined. Carbapenem-resistant
      Acinetobacter baumannii isolates were further investigated for their resistance
      mechanism via the modified Hodge test, inhibitor-potentiated disk diffusion test,
      synergy with carbonyl cyanide chlorophenylhydrazone, and PCR. Moreover, clonal
      linkage was examined via enterobacterial repetitive intergenic consensus (ERIC)
      PCR. RESULTS: Klebsiella spp was the most prevalent species in the isolates
      examined (217; 40%). Although A. baumannii represented only 10% of the total
      isolates, it showed the highest percentage of carbapenem resistance (74%). PCR
      showed that 100% of the resistant isolates carried both blaOXA-51 and blaOXA-23
      genes, 85% carried the class 1 integrase genes, and only 2.5% carried metallo
      beta-lactamase (blaVIM). ERIC-PCR indicated that isolates from different
      hospitals were genetically linked. CONCLUSIONS: These findings represent the
      first report of the alarming spread of OXA-23 carbapenemase in A. baumannii in
      Egyptian intensive care units. The spread of such strains has serious health
      consequences and requires the application of strict infection control measures.

PMID- 24084244
TI  - Impact of an international nosocomial infection control consortium
      multidimensional approach on central line-associated bloodstream infection rates
      in adult intensive care units in eight cities in India.
AB  - OBJECTIVE: To evaluate the impact of the International Nosocomial Infection
      Control Consortium (INICC) multidimensional infection control approach on central
      line-associated bloodstream infection (CLABSI) rates in eight cities of India.
      METHODS: This was a prospective, before-and-after cohort study of 35650 patients
      hospitalized in 16 adult intensive care units of 11 hospitals. During the
      baseline period, outcome surveillance of CLABSI was performed, applying the
      definitions of the CDC/NHSN (US Centers for Disease Control and
      Prevention/National Healthcare Safety Network). During the intervention, the
      INICC approach was implemented, which included a bundle of interventions,
      education, outcome surveillance, process surveillance, feedback on CLABSI rates
      and consequences, and performance feedback. Random effects Poisson regression was
      used for clustering of CLABSI rates across time periods. RESULTS: During the
      baseline period, 9472 central line (CL)-days and 61 CLABSIs were recorded; during
      the intervention period, 80898 CL-days and 404 CLABSIs were recorded. The
      baseline rate was 6.4 CLABSIs per 1000 CL-days, which was reduced to 3.9 CLABSIs
      per 1000 CL-days in the second year and maintained for 36 months of follow-up,
      accounting for a 53% CLABSI rate reduction (incidence rate ratio 0.47, 95%
      confidence interval 0.31-0.70; p=0.0001). CONCLUSIONS: Implementing the six
      components of the INICC approach simultaneously was associated with a significant
      reduction in the CLABSI rate in India, which remained stable during 36 months of
      follow-up.

PMID- 24084246
TI  - Impact of seasonality and annual immunization of elderly people upon influenza
      related hospitalization rates.
AB  - OBJECTIVE: The objective of this study was to estimate the impact of seasonality
      and immunization on hospitalization rates of elderly people in a southern
      Brazilian state. METHODS: An epidemiological study of ecological design,
      combining time-series in the period 1995-2009, was carried out. The medical
      records of individuals residing in Santa Catarina aged>=60 years were obtained
      from the Hospital Information System of the Brazilian National Health System.
      Multiple linear regression analysis was used to calculate the impact exerted by
      seasonality and by influenza immunization coverage on hospitalization rates.
      RESULTS: A decrease of 5.73% in the rate of hospitalization was observed in the
      first quarters of the years, and an increase of 8.75% in the third quarters of
      the years, showing the impact of seasonality. The results also showed that as the
      vaccination coverage rate increased 1%, a decrease of 0.1% was observed in the
      hospitalization rate. CONCLUSION: Seasonality and immunization had an impact on
      the hospitalization rates of individuals aged>=60 years in the state of Santa
      Catarina during the period studied.

PMID- 24084247
TI  - Crimean-Congo hemorrhagic fever: seroprevalence and risk factors among humans in
      Achaia, western Greece.
AB  - BACKGROUND: The Crimean-Congo hemorrhagic fever virus (CCHFV) presents a wide
      distribution, with the Balkan Peninsula being among the endemic regions. To date,
      only one CCHF case has been reported in Greece; however, based on seroprevalence
      data, there is evidence that CCHFV circulates in the country. Achaia is a
      prefecture in western Greece that has not previously been studied for CCHFV.
      OBJECTIVES: The aim of this study was to estimate the seroprevalence of CCHFV in
      humans in Achaia Prefecture, Greece, and to assess possible factors playing a
      role in seropositivity. METHODS: A total of 207 serum samples from people of all
      age groups, from both urban and rural areas, were prospectively collected and
      tested for IgG antibodies against CCHFV. RESULTS: The overall seroprevalence was
      3.4%, with significant differences among municipalities. An agro-pastoral
      occupation, contact with sheep and goats, former tick bite, increasing age, and
      living at an altitude of >=400 m, on specific land cover types, were
      significantly associated with CCHFV seropositivity. CONCLUSIONS: A relatively
      high seroprevalence was detected in a previously unstudied region of Greece,
      where CCHFV infection seems to occur mainly through tick bites. Further
      investigations are needed to identify the circulating CCHFV strains in Greece, in
      order to gain a better understanding of CCHFV ecology and epidemiology in the
      country.

PMID- 24084248
TI  - The GSTM1null (deletion) and MGMT84 rs12917 (Phe/Phe) haplotype are associated
      with bulky DNA adduct levels in human leukocytes.
AB  - Tobacco smoke and air pollutants contain carcinogens, such as polycyclic aromatic
      hydrocarbons (PAHs) and tobacco specific nitrosamines (TSNA), that are substrates
      of metabolizing enzymes generating reactive metabolites that can bind to DNA.
      Variation in the activity of these enzymes may modify the extent to which these
      metabolites can interact with DNA. We compared the levels of bulky DNA adducts in
      blood leukocytes from 93 volunteers living in Mexico City with the presence of 13
      single nucleotide polymorphisms (SNPs) in genes related to PAH and TSNA
      metabolism (AhR rs2044853, CYP1A1 rs1048943, CYP1A1 rs1048943, CYP1A1 rs1799814,
      EPHX1 rs1051740, EPHX1 rs2234922, GSTM1 null, GSTT1 null and GSTP1 rs947894), DNA
      repair (XRCC1 rs25487, ERCC2 rs13181 and MGMT rs12917) and cell cycle (TP53
      rs1042522). (32)P-postlabeling analysis was used to quantify bulky DNA adduct
      formation. Genotyping was performed using PCR-RFLP. The mean levels of bulky DNA
      adducts were 8.51+/-3.66 adducts/10(8) nucleotides (nt) in smokers and 8.38+/
      3.59 adducts/10(8) nt in non-smokers, being the difference not statistically
      significant. Without taking into account the smoking status, GSTM1 null
      individuals had a marginally significant lower adduct levels compared with GSTM1
      volunteers (p=0.0433) and individuals heterozygous for MGMT Leu/Phe had a higher
      level of bulky adducts than those who were homozygous wild type (p=0.0170). A
      multiple regression analysis model showed a significant association between the
      GSTM1 (deletion) and MGMT rs12917 (Phe/Phe) haplotype and the formation of DNA
      adducts in smokers (R(2)=0.2401, p=0.0215). The presence of these variants
      conferred a greater risk for higher adduct levels in this Mexican population.

PMID- 24084249
TI  - Getting to the heart of the matter: a trialist's approach to the use of
      nonsteroidal anti-inflammatory drugs for patients with chronic pain syndromes.
AB  - In this editorial, I refer to the relative risks associated with different
      interventions. To provide a perspective of what it means, please consider the
      risks of particular events in the placebo group of controlled trials of
      cyclooxygenase-2 inhibitors: major vascular events (0.82%) including nonfatal
      myocardial infarction (MI; 0.29%) or any MI (0.33%), any stroke (0.36%), heart
      failure (0.26%), upper gastrointestinal (GI) bleeding (0.14%) with any major GI
      complication (0.19%).

PMID- 24084250
TI  - Integrating spirituality into patient care: an essential element of person
      centered care.
AB  - Spirituality and health is a growing field of healthcare. It grew out of courses
      in spirituality and health developed for medical students in the United States.
      Research in this area over the last 30 years has also formed an evidence base for
      spirituality and health. Studies have demonstrated an association between
      spiritual beliefs and values and a variety of healthcare outcomes. More recent
      research has also shown a strong desire on the part of patients to have their
      spirituality addressed as part of their care. Studies also show that spiritual
      care has an impact on patient decision making, particularly in end-of-life care.
      The Association of American Medical Colleges developed a broad definition of
      spirituality as well as learning objectives and guidelines for teaching.
      Standards in organizations such as the American College of Physicians support
      physicians treating the whole person, that is, the body, mind, and spirit. In
      2009, National Competencies in Spirituality and Health education were developed
      in the United States with schools currently working on curriculum projects based
      on these competencies. Models are being developed for all members of the
      healthcare team to address patient distress, in cooperation with chaplains as
      spiritual care experts. The goals are to develop a biopsychosocial and spiritual
      assessment and treatment as part of compassionate whole-person care of all
      patients. 

PMID- 24084251
TI  - Abnormal left and right coronary-to-aortic arch and main and right pulmonary
      artery fistulas in a 63-year-old patient.

PMID- 24084252
TI  - Vincent van Gogh and digitalis.

PMID- 24084253
TI  - Angiosarcoma of the adrenal gland.

PMID- 24084254
TI  - Acetazolamide and sulfa allergy: how to deal with sulfa allergy at altitude?

PMID- 24084255
TI  - Molecular basis of hippocampal energy metabolism in diabetic rats: the effects of
      SOD mimic.
AB  - Hippocampal structural changes associated with diabetes-related cognitive
      impairments are well described, but their molecular background remained vague. We
      examined whether/how diabetes alters molecular basis of energy metabolism in
      hippocampus readily after diabetes onset, with special emphasis on its redox
      sensitivity. To induce diabetes, adult Mill Hill hybrid hooded rats received a
      single alloxan dose (120 mg/kg). Both non-diabetic and diabetic groups were
      further divided in two subgroups receiving (i) or not (ii) superoxide dismutase
      (SOD) mimic, [Mn(II)(pyane)Cl2] for 7 days, i.p. Treatment of the diabetic
      animals started after blood glucose level >=12 mM. Diabetes decreased protein
      levels of oxidative phosphorylation components: complex III and ATP synthase. In
      contrast, protein amounts of glyceraldehyde-3-phosphate dehydrogenase, pyruvate
      dehydrogenase, and hypoxia-inducible factor-1alpha - the key regulator of energy
      metabolism in stress conditions, were higher in diabetic animals. Treatment with
      SOD mimic restored/increased the levels of oxidative phosphorylation components
      and returned hypoxia-inducible factor-1alpha to control level, while diabetes
      induced up-regulation of glycolytic enzyme, glyceraldehyde-3-phosphate
      dehydrogenase, was additionally stimulated. To conclude, our results provide
      insight into the earliest molecular changes of energy-producing pathways in
      diabetes that may account for structural/functional disturbance of hippocampus,
      seen during disease progression. Also, data suggest [Mn(II)(pyane)Cl2] as
      potential therapeutic agent in cutting-edge approaches to threat this widespread
      metabolic disorder.

PMID- 24084257
TI  - Studies on the toxicity of an aqueous suspension of C60 nanoparticles using a
      bacterium (gen. Bacillus) and an aquatic plant (Lemna gibba) as in vitro model
      systems.
AB  - The increasing use of C60 nanoparticles and the diversity of their applications
      in industry and medicine has led to their production in a large scale. C60
      release into wastewaters and the possible accumulation in the environment has
      raised concerns about their ecotoxicological impact. In the present study, an
      aqueous suspension of C60 nanoparticles was prepared and its potential toxicity
      studied in laboratory, using a bacterium (Bacillus stearothermophilus) and an
      aquatic plant (Lemna gibba) as model systems. C60 nanoparticles inhibited the
      growth of L. gibba, in contrast to that of the bacterium. Consistently, the
      ultrastructure and respiratory activity of bacterial cells were not affected by
      C60, but the contents of chlorophylls a and b and chloroplast oxygen production
      decreased considerably in L. gibba. Altogether, our results suggest that C60
      aqueous dispersions must be viewed as an environmental pollutant, potentially
      endangering the equilibrium of aquatic ecosystems. 

PMID- 24084258
TI  - How does exposure to nickel and cadmium affect the transcriptome of yellow perch
      (Perca flavescens)--results from a 1000 candidate-gene microarray.
AB  - The molecular mechanisms underlying nickel (Ni) and cadmium (Cd) toxicity and
      their specific effects on fish are poorly understood. Documenting gene
      transcription profiles offers a powerful approach toward identifying the
      molecular mechanisms affected by these metals and to discover biomarkers of their
      toxicity. However, confounding environmental factors can complicate the
      interpretation of the results and the detection of biomarkers for fish captured
      in their natural environment. In the present study, a 1000 candidate-gene
      microarray, developed from a previous RNA-seq study on a subset of individual
      fish from contrasting level of metal contamination, was used to investigate the
      transcriptional response to metal (Ni and Cd) and non metal (temperature, oxygen,
      and diet) stressors in yellow perch (Perca flavescens). Specifically, we aimed at
      (1) identifying transcriptional signatures specific to Ni and Cd exposure, (2)
      investigating the mechanisms of their toxicity, and (3) developing a predictive
      tool to identify the sublethal effects of Ni and Cd contaminants in fish sampled
      from natural environments. A total of 475 genes displayed significantly different
      transcription levels when temperature varied while 287 and 176 genes were
      differentially transcribed at different concentrations of Ni and Cd,
      respectively. These metals were found to mainly affect the transcription level of
      genes involved in iron metabolism, transcriptional and translational processes,
      vitamin metabolism, blood coagulation, and calcium transport. In addition, a
      linear discriminant analysis (LDA) made using gene transcription levels yielded
      94% correctly reassigned samples regarding their level of metal contamination,
      which indicates the potential of the microarray to detect perch response to Cd or
      Ni effects. 

PMID- 24084256
TI  - Knockdown of AHR1A but not AHR1B exacerbates PAH and PCB-126 toxicity in
      zebrafish (Danio rerio) embryos.
AB  - Various environmental contaminants are known agonists for the aryl hydrocarbon
      receptor (AHR), which is highly conserved across vertebrate species. Due to gene
      duplication events before and after the divergence of ray- and lobe-finned
      fishes, many teleosts have multiple AHR isoforms. The zebrafish (Danio rerio) has
      three identified AHRs: AHR1A and AHR1B, the roles of which are not yet well
      elucidated, and AHR2, which has been shown to mediate the toxicity of various
      anthropogenic compounds including dioxins, polychlorinated biphenyls (PCBs), and
      polycyclic aromatic hydrocarbons (PAHs). In this study, we sought to explore the
      role of the two AHR1 isoforms in PAH- and PCB-induced toxicity in zebrafish
      embryos utilizing morpholino gene knockdown of the AHR isoforms. Knockdown of
      AHR1B did not affect the toxicity of PAH mixtures or PCB-126, whereas knockdown
      of AHR1A exacerbated the cardiac toxicity caused by PAH mixtures and PCB-126.
      Knockdown of AHR1A did not impact the mRNA expression of CYP1A, CYP1B1, and
      CYP1C1 in exposed embryos, but it did result in increased CYP1 activity in
      exposed embryos. As has been shown previously, knockdown of AHR2 resulted in
      protection from PAH- and PCB-induced cardiac deformities and prevented CYP1
      enzyme activity in exposed embryos. Co-knockdown of AHR1A and AHR2 resulted in an
      intermediate response compared to knockdown of AHR1A and AHR2 individually; co
      knockdown did not exacerbate nor protect from PAH-induced deformities and embryos
      exhibited an intermediate CYP1 enzyme activity response. In contrast, co
      knockdown of AHR1A and AHR2 did protect from PCB-126-induced deformities. These
      results suggest that AHR1A is not a nonfunctional receptor as previously thought
      and may play a role in the normal physiology of zebrafish during development
      and/or the toxicity of environmental contaminants in early life stages. 

PMID- 24084259
TI  - Optical properties of a long dynamic range chemical UV dosimeter based on solvent
      cast polyvinyl chloride (PVC).
AB  - The dosimetric properties of the recently introduced UV dosimeter based on 16 MUm
      PVC film have been fully characterised. Drying the thin film in air at 50 
      degrees C for at least 28 days was found to be necessary to minimise the
      temperature effects on the dosimeter response. This research has found that the
      dosimeter response, previously reported to be mainly to UVB, has no significant
      dependence on either exposure temperature or dose rate. The dosimeter has
      negligible dark reaction and responds to the UV radiation with high
      reproducibility. The dosimeter angular response was found to have a similar
      pattern as the cosine function but deviates considerably at angles larger than 70
      degrees . Dose response curves exhibit monotonically increasing shape and the
      dosimeter can measure more than 900 SED. This is about 3 weeks of continuous
      exposure during summer at subtropical sites. Exposures measured by the PVC
      dosimeter for some anatomical sites exposed to solar radiation for twelve
      consecutive days were comparable with those concurrently measured by a series of
      PPO dosimeters and were in line with earlier results reported in similar studies.

PMID- 24084260
TI  - Study on the interaction of homoisoflavonoids with RNA.
AB  - Homoisoflavonoids (3-benzylidene-4-chromanones) are isomers of flavonoids and
      exhibit different biological activities because of hydroxyl groups attaching to
      different positions. This study is the first attempt to locate the binding sites
      of four synthetic homoisoflavonoids: (E)-3-(3,4-dihydroxybenzylidene)-7
      methoxychroman-4-one (BMC), (E)-3-(3,4-dihydroxybenzylidene)-7-propoxychroman-4
      one (BPC), (E)-3-(4-hydroxybenzylidene)-7-methoxychroman-4-one (HBMC) and (E) 3
      (4-hydroxybenzylidene)-chroman-4-one (HBC) to RNA. The effect of the ligand
      complexation on RNA aggregation was investigated in aqueous solution at
      physiological conditions, using constant RNA concentration (6.25mM) and various
      ligand/polynucleotide (phosphate) ratios of 1/120, 1/80, 1/40, 1/20, 1/10 and
      1/5. Fourier transform infrared (FTIR) and UV-Visible spectroscopic methods were
      used to determine the ligand binding modes, the binding constants, and the
      stability of ligand-RNA complexes in aqueous solution. Spectroscopic evidence
      showed external binding of homoisoflavonoids to RNA duplex with overall binding
      constants of KBMC-RNA = 1.06(+/- 0.09) * 10(4)M(-1), KBPC-RNA = 1.11(+/- 0.15) *
      10(4)M (-1), KHBC-RNA = 3.82(+/- 0.09) * 10(3)M(-1) and KHBMC-RNA=5.82(+/- 0.04)
      * 10(3) M(-1). The affinity of homoisoflavonoid-RNA binding is in the order of
      BPC>BMC>HBMC>HBC. No biopolymer secondary structural changes were observed upon
      homoisoflavonoids interaction and RNA remains in the A-family structure in these
      complexes.

PMID- 24084261
TI  - Physical inactivity at leisure and work: a 12-month study of cardiac patients.
AB  - PURPOSE: Physical inactivity has been identified as a distinct health risk.
      However, little is known about how this can vary at leisure and work in cardiac
      patients. The aim of this study was to examine the prevalence and predictors of
      inactivity during leisure and work in the 12 months following a cardiac event in
      Australian cardiac patients. METHODS: A total of 346 patients consecutively
      admitted to hospital with acute coronary syndrome or to undergo coronary artery
      bypass graft surgery were interviewed in hospital, and 4 and 12 months later.
      Leisure and occupational physical activity was measured using the Stanford Brief
      Activity Survey. Sociodemographic, psychosocial, and clinical data were also
      collected. RESULTS: The prevalence of leisure-time physical inactivity declined
      over time, with 52% inactive preevent and 29% inactive at 12 months.
      Approximately 50% of participants were physically inactive in their work,
      regardless of whether this was measured before or after the cardiac event.
      Logistic regression revealed that the significant predictors of leisure-time
      physical inactivity at 12 months were non-home ownership (OR = 2.19; P = .007)
      and physical inactivity in leisure-time prior to the event (OR = 2.44; P = .001).
      The significant predictors of occupational physical inactivity at 12 months were
      white-collar occupation (OR = 3.10; P < .001) and physical inactivity at work
      prior to the event (OR = 12.99; P < .001). CONCLUSIONS: Preevent physical
      inactivity, socioeconomic, and clinical factors predicted both leisure and work
      inactivity after an acute cardiac event. Effective interventions could be
      designed and implemented to target those most at risk of being physically
      inactive at work or leisure.

PMID- 24084263
TI  - Endograft-assisted coil embolization of a celiac trunk aneurysm.
AB  - BACKGROUND: Celiac trunk aneurysms are rare but potential life-threatening
      lesions. Endovascular techniques are more often used for their treatment because
      of low rates of morbidity and mortality. CASE REPORT: We describe a modification
      of stent-assisted coil embolization technique more commonly used in the treatment
      of intracranial aneurysm, to exclude a 50-mm diameter celiac trunk aneurysm. The
      patient was a 67-year-old man who had a previous exclusion of a symptomatic
      aortic aneurysm, with occlusion of the inferior mesenteric and both hypogastric
      arteries. Anatomic features of the celiac trunk aneurysm and its branches do not
      allow treatment with a straight endograft or maintain direct flow to the hepatic
      artery. We then performed an endograft-assisted coil embolization of the
      aneurysm, with a straight flow line to the splenic artery. CONCLUSION: Endograft
      assisted coil embolization is a feasible and safe technique to allow selective
      embolization of the sac and the presence of direct flow to the splenic artery and
      indirect flow to the hepatic artery.

PMID- 24084262
TI  - Clinical validation of IFNgamma/IL-10 and IFNgamma/IL-2 FluoroSpot assays for the
      detection of Tr1 T cells and influenza vaccine monitoring in humans.
AB  - The type of T cell polarization and simultaneous production of multiple cytokines
      have been correlated with vaccine efficacy. ELISpot is a T cell detection
      technique optimized for the measurement of a secreted cytokine at the single cell
      level. The FluoroSpot assay differs from ELISpot by the use of multiple
      fluorescent-labeled anticytokine detection antibodies, allowing optimal
      measurement of multiple cytokines. In the present study, we show that an
      IFNgamma/IL-10 FluoroSpot assay is more sensitive than flow cytometry to detect
      Tr1 regulatory T cells, an immunosuppressive T cell population characterized by
      the production of IL-10 and IFNgamma. As many tolerogenic vaccines are designed
      to induce these Tr1 cells, this FluoroSpot test could represent a standard method
      for the detection of these cells in the future. The use of an IFNgamma/IL-2
      FluoroSpot assay during influenza vaccine monitoring showed that the influenza
      specific IL-2-producing T-cell response was the dominant response both before and
      after vaccine administration. This study therefore questions the rationale of
      using the single-color IFNgamma ELISpot as the standard technique to monitor
      vaccine-specific T-cell response. Using this same test, a trend was also observed
      between baseline levels of IFNgamma T cell response and T cell vaccine response.
      In addition, a lower IFNgamma+IL-2+ T-cell response after vaccine was observed in
      the group of patients treated with TNFalpha inhibitors (P=0.08). This study
      therefore supports the use of the FluoroSpot assay due to its robustness,
      versatility and the complementary information that it provides compared with
      ELISpot or flow cytometry to monitor vaccine-specific T-cell responses.

PMID- 24084264
TI  - Study to develop a waiting list prioritization score for varicose vein surgery.
AB  - BACKGROUND: The objective of this study was to develop a clear-cut, objective
      system for prioritization of patients on the waiting list for varicose vein
      surgery, to enable organization of access to the health service. METHODS: During
      earlier phases, we selected which variables should be taken into account for the
      prioritization scale, such as clinical presentation, varicose vein size,
      complications, work situation, and influence on quality of life. In the last
      phase, to determine the relative weight of each variable, structured surveys
      (personal interviews or by e-mail) were performed of the convenience samples from
      the groups related to the healthcare process, including patients, relatives, and
      healthcare professionals. RESULTS: The structured survey we utilized was
      administered to a sample of 762 subjects that included 290 patients, 99
      relatives, 179 general practitioners, 32 nurses, and 162 vascular surgeons. The
      final score included clinical manifestations (46.1% of relative importance), size
      of the varicose veins (8.2%), complications (18.3%), influence on quality of life
      (18.2%), and aggravating work factors (9.2%). CONCLUSIONS: The prioritization
      system agreed upon by all the groups involved could allow for objective and
      transparent prioritization and lead to the rationalization of access to varicose
      vein surgery for patients on the waiting list.

PMID- 24084265
TI  - Evaluation of superficial femoral artery remote endarterectomy for treatment of
      critical limb ischemia in patients with limited autogenous conduit.
AB  - BACKGROUND: Many patients with critical limb ischemia require infrageniculate
      bypass with a prosthetic graft due to the limited availability of autogenous
      vein. Prosthetic grafts have been shown to have inferior patency and subject the
      patient to increased infection rates when compared to bypass with autogenous
      conduit for lower extremity revascularization. In an effort to avoid the use of
      prosthetic material, we evaluated the use of remote superficial femoral artery
      endarterectomy (RSFAE) with distal autogenous revascularization in patients with
      critical limb ischemia and limited conduit. METHODS: This study is a
      retrospective review of a prospectively maintained database from January 2009 to
      September 2011. All patients undergoing RSFAE for critical limb ischemia were
      identified. Patients undergoing RSFAE with simultaneous distal revascularization
      constituted the study group. Outcome variables, including patency, time to
      healing, limb salvage, ambulatory status, and survival, were analyzed. RESULTS:
      Twenty-one patients underwent RSFAE at our institution. The study group was
      comprised of 5 patients undergoing RSFAE and adjunct distal revascularization for
      critical limb ischemia during the study period. Four patients (80%) presented
      with tissue loss, and 1 (20%) presented with ischemic rest pain. Three (60%)
      required simultaneous outflow sequential vein bypass and 2 (40%) required distal
      endovascular revascularization. The distal target vessels for bypass included the
      infrageniculate popliteal artery, posterior tibial artery, and peroneal artery.
      The mean operative time was 5.3 hours. The mean length of hospital stay was 8
      days. Technical success was 100%, and there were no early reconstruction
      failures. There was 1 popliteal wound complication, and no groin wound
      complications during the study follow-up. At 6 months postoperatively, 4 of 5
      reconstructions were patent. Two of 5 patients (40%) required percutaneous
      reintervention for restenosis at 10 and 11 months, respectively. Primary assisted
      patency was 80% with a mean follow-up of 12.6 months (range 8-22 months). The 4
      patients with tissue loss achieved initial wound healing at a mean time of 4.8
      months. The limb salvage rate was 80% and there have been no deaths. CONCLUSIONS:
      Remote superficial femoral artery endarterectomy with distal revascularization
      allows for autogenous reconstruction in patients with critical limb ischemia and
      compromised conduit by shortening bypass length. This procedure constitutes an
      appealing alternative to the use of synthetic material for lower extremity
      revascularization. Further study is needed to determine whether the long-term
      results are superior to distal composite bypass or polytetrafluoroethylene bypass
      alone.

PMID- 24084266
TI  - Excision of a permanent inferior vena cava filter with multiple vena caval
      perforations.
AB  - Perforation of an inferior vena cava filter by one the filter device hooks is a
      recognized possible complication of this device. We describe a case of surgical
      excision of a permanent inferior vena cava filter associated with multiple
      perforations of surrounding structures by each of the 6 hooks of the device.
      Structures affected include the third lumbar vertebral body, transverse
      mesocolon, the infrarenal aorta, the duodenum, and the psoas muscle. A thorough
      understanding of the filter design and adequate preoperative imaging were vital
      in planning the safe surgical excision of this device. 

PMID- 24084267
TI  - Rapid renal function deterioration: an unusual presentation of coral reef plaque.
AB  - Coral reef aorta is an uncommon variant of atherosclerotic disease. We report a
      rare presentation of rapid renal function deterioration in a patient with coral
      reef plaque protruding into the renal orifices without significant disease
      elsewhere. The patient was successfully treated with aorta endarterectomy,
      resulting in complete resolution of renal dysfunction. This case highlights the
      importance of prompt intervention for renal rescue. 

PMID- 24084268
TI  - One-week postoperative patency of lower extremity in situ bypass graft comparing
      epidural and general anesthesia: retrospective study of 822 patients.
AB  - BACKGROUND: The purpose of this study was to determine whether anesthesia affects
      graft patency after lower extremity arterial in situ bypass surgery. METHODS:
      This investigation was a retrospective study using a national database on
      vascular surgical patients at a single medical institution. We assessed a total
      of 822 patients exposed to infrainguinal in situ bypass vascular surgery over the
      period of January 2000 to September 2010. RESULTS: All patients included in the
      study (age [mean +/- SD] 70.8 +/- 9.7 years) underwent infrainguinal in situ
      bypass (n = 885) for lower extremity revascularization under epidural (n = 386)
      or general (n = 499) anesthesia. Thirty-day mortality (3.4% for epidural
      anesthesia versus 4.4% general anesthesia; P = 0.414) and comorbidity were
      comparable in the 2 groups. Graft occlusion within 7 days after surgery was
      reported in 93 patients, with a similar incidence in the epidural (10.1%) and
      general (10.8%) anesthesia groups (P = 0.730). When examining a subgroup of
      patients (n = 242) exposed to surgery on smaller vessels (femorodistal in situ
      bypass procedures, n = 253), the incidence of graft occlusion was also similar in
      the 2 groups at 14.0% and 9.4%, respectively (P = 0.262). CONCLUSION: This
      retrospective study has shown that when graft patency is evaluated 7 days after
      surgery, anesthetic choice (epidural or general anesthesia) does not influence
      outcome.

PMID- 24084269
TI  - Relining of an abdominal aortic aneurysm stent graft 9 years after placement.
AB  - We describe a case of delayed failure with an aortic stent graft 104 months after
      the graft was initially placed. This case details an endovascular strategy of
      dealing with the loss of stent graft integrity and underscores the importance of
      continued follow-up of patients with aortic stent grafts.

PMID- 24084270
TI  - Duplicated common femoral artery can be safely cannulated for femorofemoral
      cardiopulmonary bypass.
AB  - The duplicated common femoral artery can be safely cannulated for femorofemoral
      bypass, but we recommend postoperative imaging to identify potential
      complications. We found no previous reports of duplicated common femoral artery. 

PMID- 24084271
TI  - Clinical outcomes of inferior vena cava filter placement in patients with renal
      vein anomalies.
AB  - BACKGROUND: To investigate the clinical outcomes in patients with renal vein
      anomalies who undergo inferior vena cava (IVC) filter placement. METHODS:
      Contrast-enhanced computed tomography images of 410 patients who underwent IVC
      filter placement were retrospectively reviewed to detect renal vein anomalies.
      Clinical outcomes involving de novo pulmonary embolism and worsening of renal
      function were compared between patients with the location of filters placed in
      relation to the anomalous renal veins versus not in relation to any renal veins.
      RESULTS: A total of 97 (23.7%) renal vein anomalies were identified: 62 (15.1%)
      multiple right renal veins, 23 (5.6%) circumaortic left renal veins, 10 (2.4%)
      retroaortic left renal veins, and 2 (0.5%) accessory left renal veins. Frequency
      of de novo pulmonary embolism in patients with circumaortic left renal veins who
      had filters placed at or in between the 2 left renal veins was not significantly
      different from patients who underwent infra- or suprarenal filter placement (5.9%
      [1/17] vs. 3.1% [12/387]; P = 0.433). The frequency of patients who had a >25%
      decrease in estimated glomerular filtration rate after IVC filter placement was
      not significantly different whether the filter was placed in an infrarenal
      location or at or above the level of the anomalous renal veins (11.0% [37/335]
      vs. 17.6% [6/34]; P = 0.261). CONCLUSIONS: Clinical outcomes involving the
      frequency of de novo pulmonary embolism and worsening of renal function are not
      dependent on location of IVC filter placement in patients with renal vein
      anomalies.

PMID- 24084272
TI  - Usefulness of neutrophil/lymphocyte ratio as a predictor of amputation after
      embolectomy for acute limb ischemia.
AB  - BACKGROUND: The aim of this study was to examine the predictive ability of
      admission neutrophil/lymphocyte ratio (NLR) for predicting amputation in patients
      with acute limb ischemia who underwent embolectomy. METHODS: We retrospectively
      analyzed the clinical, hematologic, and amputation data of 254 patients who had
      undergone embolectomy for acute limb ischemia. There were 152 (52%) men and 93
      (48%) women, with a mean age of 66.04 +/- 13.30 years. The admission NLR was
      determined by dividing the absolute neutrophil count by the absolute lymphocyte
      count. The primary end point was determined as amputation and death. RESULTS: The
      mean duration of follow-up was 26 months. During the follow-up period, there were
      18 (7%) amputations within 30 days of surgery and 36 (15%) amputations over a
      mean follow-up of 26 months. Based on multivariate logistic regression modeling,
      no arterial back bleeding and preoperative NLR were observed to be independent
      risk factors for amputation within 30 days of surgery, and no arterial back
      bleeding and preoperative NLR were observed to be independent risk factors for
      midterm amputation for the same time period. A NLR of >=5.2 was taken as the
      cutoff based upon the receiver operating characteristic. In receiver operating
      characteristic curve analysis, a NLR >=5.2 had 83% sensitivity and 63%
      specificity in predicting amputation within 30 days of surgery and 63%
      sensitivity and 63% specificity in predicting midterm amputation. CONCLUSIONS: An
      elevated NLR is associated with a poorer limb survival after embolectomy. This
      simple, inexpensive test may therefore be added to risk stratification of these
      high-risk patients.

PMID- 24084273
TI  - Predictors of cervical bleeding after carotid endarterectomy.
AB  - BACKGROUND: The aim of this study is to determine the incidence of severe
      cervical bleeding requiring reintervention after carotid endarterectomy (CEA), to
      identify its predictive parameters, and to find out the influence of these on
      major complications. METHODS: This was a retrospective review of 502 CEAs carried
      out in 455 consecutive patients between 1995-2011 in our institution. The end
      points were: postoperative cervical bleeding that required reoperation and major
      postoperative complications (i.e., stroke, myocardial infarction, and death).
      Patients' demographics, antiplatelet and anticoagulant treatment, anaesthetic
      technique, surgical details, and perioperative management were registered. The
      end point predictors were univariate and multivariate analyzed. RESULTS: Neck
      bleeding after CEA occurred in 42 cases (8.4%), requiring reoperation in 28 cases
      (5.6%). In the univariate analysis, chronic anticoagulation and anticoagulation
      24 hours before surgery were associated with reoperation for bleeding (16.6% vs.
      4.8% [P = 0.02] and 17.8% vs. 4.7% [P = 0.014], respectively). The agent used for
      antiplatelet treatment before surgery was related to reoperation in the
      univariate analysis and was the only factor with statistical significance in the
      multivariate analysis: acetylsalicylic acid (ASA) 100 mg (2.4%), ASA 300 mg
      (1.5%), clopidogrel 75 mg (7.8%), ASA 100 mg associated with clopidogrel (3.3%),
      triflusal (5.5%), and ticlopidine (2.2%); there was a higher incidence of
      reoperation only in the group of patients who had taken clopidogrel 24 hours
      before CEA (4.7% vs. 1.05% [P = 0.06], respectively) but without statistical
      significance (odds ratio: 2; 95% confidence interval: 0.95-4.84). No reoperations
      were registered using vein patch compared to prosthetic patch (0% vs. 6.1% [P =
      0.028]). Conversion to general anesthesia (22.2% vs. 4.9% [P = 0.014]) and
      noncontrollable postoperative hypertension (6.9% vs. 2.5% [P = 0.028]) were
      associated with a higher rate of reoperation. There were no statistically
      significant differences in the reoperation rates related to bleeding for
      anesthetic technique (local versus general), surgical procedure (classic
      endarterectomy versus eversion technique), type of prosthetic patch
      (Dacron/politetrafluoroethylene), use of shunt, intraoperative dose of heparin,
      protamine reversal, activated clotting time monitoring, or surgeon qualification
      level. The combined rate of stroke mortality was 2.6%. Reoperation for bleeding
      was not associated with an increased rate of thrombosis, stroke, death, or injury
      of cranial nerves. CONCLUSIONS: Postoperative severe bleeding after carotid
      surgery in our institution is not an uncommon complication. Its incidence is
      within the range reported in the literature, but it is not associated with major
      complications or mortality. Antiplatelet treatment with clopidogrel is the main
      risk factor associated with reintervention. Other factors, such as coagulation
      control, postoperative hypertension management, and the use of an autologous
      patch, could help reduce its incidence.

PMID- 24084274
TI  - Elective treatment of abdominal aortic aneurysm is reasonable in patients >85
      years of age.
AB  - BACKGROUND: The numbers of patients >85 years of age referred for abdominal
      aortic aneurysm (AAA) repair have increased in recent decades. With the
      population aging, increased screening of AAA, and introduction of less invasive
      surgical techniques, vascular surgeons will be treating more elderly patients.
      Few data are available for estimating the risks and benefits of prophylactic
      repair among those with such an advanced age. The aim of this single-center study
      was to evaluate the short-term to midterm results after AAA repair in patients
      >85 years of age. METHODS: Between 2004 and 2012, data of patients >85 years old
      who required an elective AAA repair at our institution were collected
      prospectively. According to the current guidelines, patients underwent
      endovascular aneurysm repair (EVAR) each time the aortic anatomy was suitable.
      Open repair (OR) was performed in those patients with hostile proximal neck
      anatomy and/or severe iliac tortuosity. Type of repair (EVAR or OR) and
      perioperative and midterm outcomes were analyzed. Primary end points were 30-day
      mortality and midterm survival. RESULTS: Among 1016 patients undergoing elective
      AAA repair during the study period, 59 (5.8%) were >=85 years of age (54 men,
      mean age 87 +/- 2 years), with a mean aneurysm diameter of 61.5 +/- 20.3 mm.
      Thirty-three patients (56%) underwent EVAR and 26 (44%) had an OR. Thirty-day
      mortality was 6.7% (6% with EVAR and 7.6% with OR, P <0.05). Mean follow-up was
      24.7 +/- 18 months. Kaplan-Meier analyses for survival were 85.5%, 64.5%, and 50%
      at 1, 3, and 5 years, respectively. No aneurysm-related death was observed during
      follow-up. CONCLUSION: Elective repair may be proposed in patients >85 years of
      age in cases of threatening AAA, showing acceptable perioperative mortality and
      reasonable midterm survival results. Even if EVAR did not seem to offer
      significant benefits in perioperative mortality in our study, it appears
      reasonable to suggest this less invasive technique as first-line treatment in
      cases of suitable anatomy in such an advanced-age population.

PMID- 24084275
TI  - Treatment of infected abdominal aortic aneurysm caused by Salmonella.
AB  - BACKGROUND: We reviewed the outcomes of patients treated for nontyphoidal
      Salmonella-infected abdominal aortic aneurysm (AAA) treatment at a single center.
      METHODS: This was a retrospective chart review of 26 patients with nontyphoidal
      Salmonella-infected AAA. Four patients underwent medical therapy alone, while 22
      patients underwent surgical therapy. Revascularization method selection was
      dependent on preoperative antibiotic response in the surgical therapy group.
      RESULTS: The in-hospital mortality rate for the surgical therapy group was 14%,
      while the rate for the medical therapy group was 100%. Overall survival for the
      surgical therapy group was 82%, while the reinfection rate was 9%. In the
      surgical therapy group, 2 patients had periaortic abscesses and underwent in situ
      prosthetic graft replacement; none developed graft-related complications or died
      in the hospital. Kaplan-Meier analysis and log-rank testing revealed no
      significant differences in graft-related complication and overall survival rates
      between in situ prosthetic graft group and extra-anatomic bypass group.
      Salmonella choleraesuis had a higher antimicrobial resistance rate than other
      isolates. The predictors of survival were clinical presentation of abdominal pain
      and receiving surgical therapy. CONCLUSIONS: If patients with Salmonella-infected
      AAAs have good responses to preoperative antibiotic therapy, in situ prosthetic
      graft replacement is a viable revascularization method, even in the situation of
      periaortic abscess presentation formation.

PMID- 24084276
TI  - The Ross procedure: outcomes at 20 years.
AB  - OBJECTIVES: Our study examines the outcomes of the Ross procedure in a cohort of
      212 patients prospectively followed with clinical and echocardiographic
      assessments. METHODS: Patients' mean age was 34 +/- 9 years; 66% were men and 82%
      had congenital aortic valve disease. The median follow-up was 13.8 years.
      Patients who had reoperations continued to be followed and entered into the
      survival analysis. RESULTS: There was 1 operative death as well as 9 late deaths
      (3 in patients who no longer had the Ross). Survival at 20 years was 93.6% and
      similar to the general population matched for age and sex. Fifteen patients
      required reoperations on the pulmonary autograft (4 repairs and 11 replacements),
      8 on the pulmonary homograft, and 4 other cardiac procedures. At 20 years the
      freedom from reoperation on the pulmonary autograft was 81.8% and on the
      pulmonary homograft was 92.7%, and in both was 79.9%. Preoperative aortic
      insufficiency, aortic annulus diameter >=15 mm/m(2), and being a man were
      associated with increased risk of reoperation on the pulmonary autograft. Twenty
      six patients developed aortic insufficiency greater than mild and 25 patients
      developed pulmonary homograft dysfunction (defined as moderate or severe
      insufficiency and/or peak systolic gradient of >40 mm Hg). At 20 years the
      freedom from aortic insufficiency was 62.6% and freedom from pulmonary valve
      dysfunction was 53.5%. CONCLUSIONS: Survival after the Ross procedure in this
      cohort was similar to the general population. Dilated aortic annulus and aortic
      insufficiency were associated with increased risk of developing aortic
      insufficiency. Pulmonary homograft dysfunction was common at 20 years.

PMID- 24084277
TI  - Association between Technical Performance Scores and neurodevelopmental outcomes
      after congenital cardiac surgery.
AB  - OBJECTIVES: Technical Performance Score (TPS) has been shown to have a strong
      association with early and late outcomes after congenital cardiac surgery, with
      greater morbidity and reintervention in children with major residual lesions (TPS
      class 3). We sought to explore the effect of TPS on the neurodevelopmental
      outcomes. METHODS: All infants undergoing cardiac surgery, excluding those with
      trisomy 21, were offered neurodevelopmental testing at 1 year of age using the
      Bayley Scales of Infant Development, 3rd edition. TPSs from the discharge
      echocardiograms were graded as class 1 (optimal), class 2 (minor residual), or
      class 3 (major residual). Multivariate regression analysis was performed using
      patient characteristics and preoperative variables. RESULTS: Neurodevelopmental
      testing was performed in 140 patients at a median age of 16 months. Of these, 28
      (20%) had single ventricle palliation; 39 (28%) were in Risk Adjustment for
      Congenital Heart Surgery category 4 to 6. Significant differences between the
      groups were found in the cognitive (P = .01) and motor (P = .05) domains, with
      subjects in TPS class 3 having significantly lower cognitive and motor composite
      scores. The scores did not vary significantly according to single ventricle
      versus biventricular repair or Risk Adjustment for Congenital Heart Surgery
      categorization. In multivariate modeling, class 3 TPS remained significantly
      associated with a lower Bayley cognitive score (P = .02), with a trend toward a
      lower Bayley motor score (P = .08). CONCLUSIONS: We found that TPS is an
      independent predictor of neurodevelopmental outcomes after infant heart surgery.
      Future research should explore whether a structured program of intraoperative
      recognition and intervention on residual lesions can improve the TPS and
      neurodevelopmental outcomes.

PMID- 24084278
TI  - Discussion.

PMID- 24084279
TI  - Historical perspectives of The American Association for Thoracic Surgery: Frank
      Gerbode (1907-1984).

PMID- 24084280
TI  - Anomalous aortic origin of the coronary artery: does pulmonary artery
      translocation affect coronary artery course?

PMID- 24084281
TI  - Discussion.

PMID- 24084282
TI  - Discussion.

PMID- 24084283
TI  - Arterial grafts balance survival between incomplete and complete
      revascularization: a series of 1000 consecutive coronary artery bypass graft
      patients with 98% arterial grafts.
AB  - OBJECTIVE: Coronary artery bypass grafting (CABG) with incomplete
      revascularization (ICR) is thought to decrease survival. We studied the survival
      of patients with ICR undergoing total arterial grafting. METHODS: In a
      consecutive series of all-comer 1000 patients with isolated CABG, operative and
      midterm survival were assessed for patients undergoing complete versus ICR, with
      odds ratios and hazard ratios, adjusted for European System for Cardiac Operative
      Risk Evaluation category, CABG urgency, age, and comorbidities. RESULTS: In this
      series of 1000 patients with 98% arterial grafts (2922 arterial, 59 vein grafts),
      73% of patients with multivessel disease received bilateral internal mammary
      artery grafts. ICR occurred in 140 patients (14%). Operative mortality was 3.8%
      overall, 8.6% for patients with ICR, and 3.2% for patients with complete
      revascularization (P = .008). For operative mortality using multivariable
      logistic regression, after controlling for European System for Cardiac Operative
      Risk Evaluation category (P < .001) and CABG urgency (P = .03), there was no
      evidence of a statistically significant increased risk of death due to ICR (odds
      ratio, 1.73; 95% confidence interval, 0.80-3.77). For midterm follow-up (median,
      54 months [interquartile range, 27-85 months]), after controlling for European
      System for Cardiac Operative Risk Evaluation category (P < .001) and
      comorbidities (P = .017) there was a significant interaction between age >= 80
      years and ICR (P = .017) in predicting mortality. The adjusted hazard ratio
      associated with ICR for patients older than age 80 years was 5.7 (95% confidence
      interval, 1.8-18.0) versus 1.2 (95% confidence interval, 0.7-2.1) for younger
      patients. CONCLUSIONS: This is the first study to suggest that ICR in patients
      with mostly arterial grafts is not associated with decreased survival
      perioperatively and at midterm in patients younger than age 80 years. Arterial
      grafting, because of longevity, may balance survival between complete
      revascularization and ICR.

PMID- 24084285
TI  - A modified approach to aortic root reconstruction in children: an extended 2
      patch root enlargement technique.

PMID- 24084284
TI  - Off-pump epicardial ventricular reconstruction restores left ventricular twist
      and reverses remodeling in an ovine anteroapical aneurysm model.
AB  - OBJECTIVE: The loss of normal apical rotation is associated with left ventricular
      (LV) remodeling and systolic dysfunction in patients with congestive heart
      failure after myocardial infarction. The objective of the present study was to
      evaluate the effect of epicardial ventricular reconstruction, an off-pump, less
      invasive surgical reshaping technique, on myocardial strain, LV twist, and the
      potential alteration of myocardial fiber orientation in an ovine model of LV
      anteroapical aneurysm. METHODS: LV anteroapical myocardial infarction was induced
      by coil embolization of the left anterior descending artery. Eight weeks after
      occlusion, epicardial ventricular reconstruction was performed using left
      thoracotomy under fluoroscopic guidance in 8 sheep to completely exclude the
      scar. The peak systolic longitudinal/circumferential strains and LV twist were
      evaluated using speckle tracking echocardiography before (baseline), after device
      implantation, and at 6 weeks of follow-up. RESULTS: Epicardial ventricular
      reconstruction was completed in all sheep without any complications. Immediately
      after device implantation, LV twist significantly increased (4.18 +/- 1.40 vs
      baseline 1.97 +/- 1.92; P = .02). The ejection fraction had increased 17% and LV
      end-systolic volume had decreased 40%. The global longitudinal strain increased
      from -5.3% to -9.1% (P < .05). Circumferential strain increased in both middle
      and apical LV segments, with the greatest improvement in the inferior lateral
      wall (from -11.4% to -20.6%, P < .001). These effects were maintained >=6 weeks
      after device implantation without redilation. CONCLUSIONS: Less invasive than
      alternative therapies, epicardial ventricular reconstruction on the off-pump
      beating heart can restore LV twist and systolic strain and reverse LV remodeling
      in an ovine anteroapical aneurysm model.

PMID- 24084287
TI  - Discussion.

PMID- 24084286
TI  - Pulmonary vein stenosis and the pathophysiology of "upstream" pulmonary veins.
AB  - BACKGROUND: Surgical and catheter-based interventions on pulmonary veins are
      associated with pulmonary vein stenosis (PVS), which can progress diffusely
      through the "upstream" pulmonary veins. The mechanism has been rarely studied. We
      used a porcine model of PVS to assess disease progression with emphasis on the
      potential role of endothelial-mesenchymal transition (EndMT). METHODS: Neonatal
      piglets underwent bilateral pulmonary vein banding (banded, n = 6) or sham
      operations (sham, n = 6). Additional piglets underwent identical banding and
      stent implantation in a single-banded pulmonary vein 3 weeks postbanding
      (stented, n = 6). At 7 weeks postbanding, hemodynamics and upstream PV pathology
      were assessed. RESULTS: Banded piglets developed pulmonary hypertension. The
      upstream pulmonary veins exhibited intimal thickening associated with features of
      EndMT, including increased transforming growth factor (TGF)-beta1 and Smad
      expression, loss of endothelial and gain of mesenchymal marker expression, and
      coexpression of endothelial and mesenchymal markers in banded pulmonary vein
      intimal cells. These immunopathologic changes and a prominent myofibroblast
      phenotype in the remodeled pulmonary veins were consistently identified in
      specimens from patients with PVS, in vitro TGF-beta1-stimulated cells isolated
      from piglet and human pulmonary veins, and human umbilical vein endothelial
      cells. After stent implantation, decompression of a pulmonary vein was associated
      with reappearance of endothelial marker expression, suggesting the potential for
      plasticity in the observed pathologic changes, followed by rapid in-stent
      restenosis. CONCLUSIONS: Neonatal pulmonary vein banding in piglets recapitulates
      critical aspects of clinical PVS and highlights a pathologic profile consistent
      with EndMT, supporting the rationale for evaluating therapeutic strategies
      designed to exploit reversibility of upstream pulmonary vein pathology.

PMID- 24084288
TI  - Management of tricuspid regurgitation in congenital heart disease: is survival
      better with valve repair?
AB  - OBJECTIVE: Tricuspid valve (TV) regurgitation in congenital heart disease
      includes a heterogeneous group of lesions, and few series have documented the
      outcomes. METHODS: We reviewed the records of 553 patients with congenital heart
      disease who had undergone TV surgery for tricuspid regurgitation from January
      1993 to December 2010. Patients with Ebstein malformation were excluded. Their
      mean age was 32 +/- 21 years, and 300 were female (54%). The most common
      diagnoses were conotruncal anomaly in 216 patients (39%), previous ventricular
      septal defect closure in 83 (15%), atrioventricular septal defect in 77 (14%),
      and pulmonary atresia with an intact ventricular septum in 11 (2%). Preoperative
      right-sided heart failure was present in 124 patients (22%), and 55 patients
      (10%) had pulmonary hypertension. RESULTS: TV repair was performed in 442 (80%)
      and TV replacement in 111 (20%) patients. Repeat sternotomy was performed in 415
      patients (75%). Previous TV repair was present in 44 patients (8%); of these, 17
      (38.6%) underwent repeat TV repair. The overall early mortality was 3.1% (17
      patients) and was 2.5% for TV repair and 5.4% for TV replacement (P = .001). The
      mean follow-up period was 4.5 +/- 4.1 years (maximum, 18). The overall survival
      at 1, 5, and 10 years was 97%, 93%, and 85%, respectively. Survival was better
      for patients with repair than with replacement. TV repair was an independent
      predictor of better survival (P = .001). CONCLUSIONS: Important tricuspid
      regurgitation can occur with a variety of congenital diagnoses. Early mortality
      is low and late survival is superior with tricuspid repair than with valve
      replacement. Surgical treatment of tricuspid regurgitation in congenital heart
      disease should be performed before the onset of heart failure.

PMID- 24084289
TI  - Expanding relevance of aortic valve repair-is earlier operation indicated?
AB  - OBJECTIVES: To define the durability of aortic valve repair (AVRep) and the
      effect of surgical timing on late survival. METHODS: From June 1986 to June 2011,
      331 patients underwent elective AVRep for aortic regurgitation (mean age, 53 +/-
      17 years; 76% men). The repair methods included commissuroplasty (n = 270; 81%),
      triangular resection and plication (n = 106; 32%), resuspension or cusp
      shortening (n = 102; 31%), and perforation closure (n = 23; 7%). RESULTS: In
      hospital mortality was 0.6% (2 of 332). Four patients (1%) experienced early
      repair failure; two underwent repeat repair. Overall survival was 91% and 81% at
      5 and 10 years, respectively. After adjusting for age, greater left ventricular
      end-systolic dimension (per 5 mm; hazard ratio [HR], 1.49; 95% confidence
      interval [CI], 1.23-1.79; P < .001) and lower ejection fraction (per 5%; HR,
      1.42; 95% CI, 1.25-1.63; P <= .001) were significant predictors of long-term
      mortality. Patients with ejection fraction < 50% and left ventricular end
      systolic dimension > 50 mm had significantly greater odds of late death (HR,
      3.46; 95% CI, 2.05-5.82; P < .001 and HR, 2.08; 95% CI, 1.05-4.12; P = .036,
      respectively). The risk of aortic valve reoperation was 10% and 21% at 5 and 10
      years, respectively. The presence of severe aortic regurgitation (HR, 2.2; 95%
      CI, 1.1-5.06; P = .02) and more than mild regurgitation at discharge (HR, 5.87;
      95% CI, 2.67-12.68; P <= .0001) were predictors of late reoperation. Freedom from
      other valve-related events was 94% and 91% at 5 and 10 years, respectively. Forty
      seven patients (21%) with intact valve repair were using warfarin at the last
      follow-up visit. CONCLUSIONS: AVRep can be performed with excellent late survival
      and freedom from valve-related events. Awaiting the onset of ventricular
      dysfunction increases the risk of late mortality, warranting earlier
      consideration of AVRep for patients with suitable anatomy.

PMID- 24084291
TI  - Lineage diversification and recombination in type-4 human astroviruses.
AB  - Human astroviruses (HAstVs) are important enteric pathogens and can be classified
      genetically and antigenically into eight types. During surveillance of HAstVs in
      Italy, type-4 HAstVs were detected only sporadically and found to cluster into
      two distinct genetic groups. Upon sequence analysis of the 3' end of the
      polymerase gene (ORF1b) and of the full-length ORF2, the 2008 type-4 HAstV
      strains were characterised as a novel ORF2 genetic lineage, designated as 4c. The
      2008 type-4 HAstVs also shared the ORF1b gene with similar HAstV-4c strains
      detected globally, thus displaying a conserved ORF1b/ORF2 asset. By interrogation
      of the databases, this novel lineage 4c accounted for 60.8% of the type-4 strains
      identified worldwide and the vast majority of recent type-4 HAstVs. The 2002 type
      4 HAstVs displayed a type-4b ORF2, whereas in the ORF1b they resembled type-1
      HAstVs. This inconsistency suggests a possible recombinant origin, with the RNA
      switch taking place upstream the ORF1b/ORF2 junction region. Also, recombination
      likely played a role in the diversification of the ORF2 of the three type-4
      lineages. Multi-target analysis is required for appropriate characterisation and
      identification of recombinant HAstVs. 

PMID- 24084290
TI  - Purifying selection in porcine reproductive and respiratory syndrome virus ORF5a
      protein influences variation in envelope glycoprotein 5 glycosylation.
AB  - Porcine reproductive and respiratory syndrome virus ORF5a protein is encoded in
      an alternate open reading frame upstream of the major envelope glycoprotein (GP5)
      in subgenomic mRNA5. Bioinformatic analysis of 3466 type 2 PRRSV sequences showed
      that the two proteins have co-evolved through a fine balance of purifying codon
      usage to maintain a conserved RQ-rich motif in ORF5a protein, while eliciting a
      variable N-linked glycosylation motif in the alternative GP5 reading frame.
      Conservation of the ORF5a protein RQ-motif also explains an anomalous uracil
      desert in GP5 hypervariable glycosylation region. The N-terminus of the mature
      GP5 protein was confirmed to start with amino acid 32, the hypervariable region
      of the ectodomain. Since GP5 glycosylation variability is assumed to result from
      immunological selection against neutralizing antibodies, these findings show that
      an alternative possibility unrelated to immunological selection not only exists,
      but provides a foundation for investigating previously unsuspected aspects of
      PRRSV biology. Understanding functional consequences of subtle nucleotide
      sequence modifications in the region responsible for critical function in ORF5a
      protein and GP5 glycosylation is essential for rational design of new vaccines
      against PRRS. 

PMID- 24084293
TI  - Response to Horn and Kahler.

PMID- 24084292
TI  - The Framingham Heart Study and the epidemiology of cardiovascular disease: a
      historical perspective.
AB  - On Sept 29, 2013, the Framingham Heart Study will celebrate 65 years since the
      examination of the first volunteer in 1948. During this period, the study has
      provided substantial insight into the epidemiology and risk factors of
      cardiovascular disease. The origins of the study are closely linked to the
      cardiovascular health of President Franklin D Roosevelt and his premature death
      from hypertensive heart disease and stroke in 1945. In this Review we describe
      the events leading to the foundation of the Framingham Heart Study, and provide a
      brief historical overview of selected contributions from the study. 

PMID- 24084294
TI  - The influence of saponins on cell membrane cholesterol.
AB  - We studied the influence of structurally different saponins on the cholesterol
      content of cellular membranes. Therefore a cell culture model using ECV-304
      urinary bladder carcinoma cells was developed. To measure the cholesterol content
      we used radiolabeled (3)H-cholesterol which is chemically and physiologically
      identical to natural cholesterol. The cells were pre-incubated with (3)H
      cholesterol and after a medium change, they were treated with saponins to assess
      a saponin-induced cholesterol liberation from the cell membrane. In another
      experiment the cells were pre-incubated with saponins and after a medium change,
      they were treated with (3)H-cholesterol to assess a saponin-induced inhibition of
      cholesterol uptake into the cell membrane. Furthermore, the membrane toxicity of
      all applied saponins was analyzed using extracellular LDH quantification and the
      general cytotoxicity was analyzed using a colorimetric MTT-assay and DNA
      quantification. Our results revealed a correlation between membrane toxicity and
      general cytotoxicity. We also compared the results from the experiments on the
      saponin-induced cholesterol liberation as well as the saponin-induced inhibition
      of cholesterol uptake with the membrane toxicity. A significant reduction in the
      cell membrane cholesterol content was noted for those saponins who showed
      membrane toxicity (IC50 <60 MUM). These potent membrane toxic saponins either
      liberated (3)H-cholesterol from intact cell membranes or blocked the integration
      of supplemented (3)H-cholesterol into the cell membrane. Saponins with little
      influence on the cell membrane (IC50 >100 MUM) insignificantly altered the cell
      membrane cholesterol content. The results suggested that the general cytotoxicity
      of saponins is mainly dependent on their membrane toxicity and that the membrane
      toxicity might be caused by the loss of cholesterol from the cell membrane. We
      also analyzed the influence of a significantly membrane toxic saponin on the
      cholesterol content of intracellular membranes such as those of endosomes and
      lysosomes. In these experiments ECV-304 cells were either incubated with (3)H
      cholesterol or with (3)H-cholesterol and 5 MUM saponin. After isolation of the
      endosomes/lysosomes their (3)H-cholesterol content was measured. A significant
      influence of the saponins on the cholesterol content of endosomal/lysosomal
      membranes was not detected.

PMID- 24084295
TI  - Labeling of islet cells with iron oxide nanoparticles through DNA hybridization
      for highly sensitive detection by MRI.
AB  - A labeling method for islet cells with superparamagnetic iron oxide nanoparticles
      (SPIOs) based on DNA hybridization is proposed for monitoring of transplanted
      islets by magnetic resonance imaging (MRI). The surfaces of SPIOs were modified
      by via Michael reaction by reacting oligo-(deoxyadenylic acid)-bearing a terminal
      thiol group at the 5'-end ((dA)20-SH) with maleic acid functional groups on the
      SPIOs. The SPIOs were immobilized on islet cells which had been pretreated with
      oligo-(thymidylic acid)-poly(ethylene glycol)-phospholipid conjugates ((dT)20-PEG
      DPPE) through DNA hybridization. Transmission electron microscopy observations
      revealed that SPIOs were initially anchored on the islet cell surfaces and
      subsequently transferred to endosomes or exfoliated with time. The SPIO-labeled
      islet cells could be clearly detected as dark spots by T2(*)-weighted MR image,
      whereas non-labeled islet cells could not be detected.

PMID- 24084296
TI  - In vitro structure-activity relationships of aplysinopsin analogs and their in
      vivo evaluation in the chick anxiety-depression model.
AB  - Aplysinopsins are tryptophan-derived natural products that have been isolated
      from a variety of marine organisms and have been shown to possess a range of
      biological activities. In vitro receptor binding assays showed that of the 12
      serotonin receptor subtypes, analogues showed a high affinity for the 5-HT2B and
      5-HT2C receptor subtypes, with selectivity for 5-HT2B over 5-HT2C. While no
      conclusions could be drawn about the number and position of N-methylations,
      bromination at C-4 and C-5 of the indole ring resulted in greater binding
      affinities, with Ki's as low as 35 nM. This data, combined with previous
      knowledge of the CNS activity of aplysinopsin analogs, suggested that these
      compounds may have potential as leads for antidepressant drugs. Compounds 3c, 3u,
      and 3x were evaluated in the chick anxiety-depression model to assess their in
      vivo efficacy. Compound 3c showed a modest antidepressant effect at a dose of 30
      nM/kg in the animal model.

PMID- 24084297
TI  - Fluorescent indicator displacement assay of ligands targeting 10 microRNA
      precursors.
AB  - Fluorescent indicator displacement (FID) assay is a rapid and convenient assay
      for identifying new ligands that bind to the target molecules. In our previous
      studies, we have shown that a series of 2,7-diaminoalkoxy xanthone and
      thioxanthone derivatives can be used as fluorescent indicators for detecting the
      interaction between RNA and a ligand. The xanthone and thioxanthone fluorochromes
      showed efficient fluorescence quenching upon binding to target RNA. Subsequent
      displacement of the bound-fluorochrome with a ligand that binds more strongly to
      the target RNA led to the recovery of the fluorescence by releasing the
      fluorochrome from RNA. Here we report a pilot screening of a chemical library
      that contains 9600 structurally diverse compounds for molecules that bind to a
      specific miRNA precursor using the FID assay. 

PMID- 24084298
TI  - A quantitative cell migration assay for murine enteric neural progenitors.
AB  - Neural crest cells (NCC) are a transient and multipotent cell population that
      originates from the dorsal neural tube and migrates extensively throughout the
      developing vertebrate embryo. In addition to providing peripheral glia and
      neurons, NCC generate melanocytes as well as most of the cranio-facial skeleton.
      NCC migration and differentiation is controlled by a combination of their axial
      origin along the neural tube and their exposure to regionally distinct
      extracellular cues. Such contribution of extracellular ligands is especially
      evident during the formation of the enteric nervous system (ENS), a complex
      interconnected network of neural ganglia that locally controls (among other
      things) gut muscle movement and intestinal motility. Most of the ENS is derived
      from a small initial pool of NCC that undertake a long journey in order to
      colonize - in a rostral to caudal fashion - the entire length of the prospective
      gut. Among several signaling pathways known to influence enteric NCC
      colonization, GDNF/RET signaling is recognized as the most important. Indeed,
      spatiotemporally controlled secretion of the RET ligand GDNF by the gut
      mesenchyme is chiefly responsible for the attraction and guidance of RET
      expressing enteric NCC to and within the embryonic gut. Here, we describe an ex
      vivo cell migration assay, making use of a transgenic mouse line possessing
      fluorescently labeled NCC, which allows precise quantification of enteric NCC
      migration potential in the presence of various growth factors, including GDNF. 

PMID- 24084299
TI  - Designing and using computer simulations in medical education and training: an
      introduction.
AB  - Computer-based technologies informed by the science of learning are becoming
      increasingly prevalent in education and training. For the Department of Defense
      (DoD), this presents a great potential advantage to the effective preparation of
      a new generation of technologically enabled service members. Military medicine
      has broad education and training challenges ranging from first aid and personal
      protective skills for every service member to specialized combat medic training;
      many of these challenges can be met with gaming and simulation technologies that
      this new generation has embraced. However, comprehensive use of medical games and
      simulation to augment expert mentorship is still limited to elite medical
      provider training programs, but can be expected to become broadly used in the
      training of first responders and allied health care providers. The purpose of
      this supplement is to review the use of computer games and simulation to teach
      and assess medical knowledge and skills. This review and other DoD research
      policy sources will form the basis for development of a research and development
      road map and guidelines for use of this technology in military medicine. 

PMID- 24084300
TI  - Cognitive task analysis-based design and authoring software for simulation
      training.
AB  - The development of more effective medical simulators requires a collaborative
      team effort where three kinds of expertise are carefully coordinated: (1)
      exceptional medical expertise focused on providing complete and accurate
      information about the medical challenges (i.e., critical skills and knowledge) to
      be simulated; (2) instructional expertise focused on the design of simulation
      based training and assessment methods that produce maximum learning and transfer
      to patient care; and (3) software development expertise that permits the
      efficient design and development of the software required to capture expertise,
      present it in an engaging way, and assess student interactions with the
      simulator. In this discussion, we describe a method of capturing more complete
      and accurate medical information for simulators and combine it with new
      instructional design strategies that emphasize the learning of complex knowledge.
      Finally, we describe three different types of software support
      (Development/Authoring, Run Time, and Post Run Time) required at different stages
      in the development of medical simulations and the instructional design elements
      of the software required at each stage. We describe the contributions expected of
      each kind of software and the different instructional control authoring support
      required. 

PMID- 24084301
TI  - Using cognitive task analysis to develop simulation-based training for medical
      tasks.
AB  - Pressures to increase the efficacy and effectiveness of medical training are
      causing the Department of Defense to investigate the use of simulation
      technologies. This article describes a comprehensive cognitive task analysis
      technique that can be used to simultaneously generate training requirements,
      performance metrics, scenario requirements, and simulator/simulation requirements
      for medical tasks. On the basis of a variety of existing techniques, we developed
      a scenario-based approach that asks experts to perform the targeted task multiple
      times, with each pass probing a different dimension of the training development
      process. In contrast to many cognitive task analysis approaches, we argue that
      our technique can be highly cost effective because it is designed to accomplish
      multiple goals. The technique was pilot tested with expert instructors from a
      large military medical training command. These instructors were employed to
      generate requirements for two selected combat casualty care tasks
      cricothyroidotomy and hemorrhage control. Results indicated that the technique is
      feasible to use and generates usable data to inform simulation-based training
      system design. 

PMID- 24084302
TI  - Use of cognitive task analysis to guide the development of performance-based
      assessments for intraoperative decision making.
AB  - BACKGROUND: There is a paucity of performance-based assessments that focus on
      intraoperative decision making. The purpose of this article is to review the
      performance outcomes and usefulness of two performance-based assessments that
      were developed using cognitive task analysis (CTA) frameworks. METHODS:
      Assessment-A used CTA to create a "think aloud" oral examination that was
      administered while junior residents (PGY 1-2's, N = 69) performed a porcine-based
      laparoscopic cholecystectomy. Assessment-B used CTA to create a simulation-based,
      formative assessment of senior residents' (PGY 4-5's, N = 29) decision making
      during a laparoscopic ventral hernia repair. In addition to survey-based
      assessments of usefulness, a multiconstruct evaluation was performed using eight
      variables. RESULTS: When comparing performance outcomes, both approaches revealed
      major deficiencies in residents' intraoperative decision-making skills.
      Multiconstruct evaluation of the two CTA approaches revealed assessment method
      advantages for five of the eight evaluation areas: (1) Cognitive Complexity, (2)
      Content Quality, (3) Content Coverage, (4) Meaningfulness, and (5) Transfer and
      Generalizability. CONCLUSIONS: The two CTA performance assessments were useful in
      identifying significant training needs. While there are pros and cons to each
      approach, the results serve as a useful blueprint for program directors seeking
      to develop performance-based assessments for intraoperative decision making.

PMID- 24084303
TI  - Balancing physiology, anatomy and immersion: how much biological fidelity is
      necessary in a medical simulation?
AB  - Physiology and anatomy can be depicted at varying levels of fidelity in a medical
      simulation or training encounter. Another factor in a medical simulation concerns
      design features intended to engage the learner through a sense of immersion.
      Physiology can be simulated by various means including physiology engines,
      complex state machines, simple state machines, kinetic models, and static
      readouts. Each approach has advantages in terms of complexity of development and
      impact on the learner. Such factors are detailed within the article. Various
      other biological, hardware-based, and virtual models are used in medical training
      with varying levels of fidelity. For many medical simulation-based educational
      experiences, low-fidelity approaches are often adequate if not preferable. 

PMID- 24084304
TI  - Cost considerations in using simulations for medical training.
AB  - This article reviews simulation used for medical training, techniques for
      assessing simulation-based training, and cost analyses that can be included in
      such assessments. Simulation in medical training appears to take four general
      forms: human actors who are taught to simulate illnesses and ailments in
      standardized ways; virtual patients who are generally presented via computer
      controlled, multimedia displays; full-body manikins that simulate patients using
      electronic sensors, responders, and controls; and part-task anatomical
      simulations of various body parts and systems. Techniques for assessing costs
      include benefit-cost analysis, return on investment, and cost-effectiveness
      analysis. Techniques for assessing the effectiveness of simulation-based medical
      training include the use of transfer effectiveness ratios and incremental
      transfer effectiveness ratios to measure transfer of knowledge and skill provided
      by simulation to the performance of medical procedures. Assessment of costs and
      simulation effectiveness can be combined with measures of transfer using
      techniques such as isoperformance analysis to identify ways of minimizing costs
      without reducing performance effectiveness or maximizing performance without
      increasing costs. In sum, economic analysis must be considered in training
      assessments if training budgets are to compete successfully with other
      requirements for funding. 

PMID- 24084305
TI  - Assessment methodology for computer-based instructional simulations.
AB  - Computer-based instructional simulations are becoming more and more ubiquitous,
      particularly in military and medical domains. As the technology that drives these
      simulations grows ever more sophisticated, the underlying pedagogical models for
      how instruction, assessment, and feedback are implemented within these systems
      must evolve accordingly. In this article, we review some of the existing
      educational approaches to medical simulations, and present pedagogical
      methodologies that have been used in the design and development of games and
      simulations at the University of California, Los Angeles, Center for Research on
      Evaluation, Standards, and Student Testing. In particular, we present a
      methodology for how automated assessments of computer-based simulations can be
      implemented using ontologies and Bayesian networks, and discuss their advantages
      and design considerations for pedagogical use. 

PMID- 24084306
TI  - Application of national testing standards to simulation-based assessments of
      clinical palpation skills.
AB  - With the advent of simulation technology, several types of data acquisition
      methods have been used to capture hands-on clinical performance. Motion sensors,
      pressure sensors, and tool-tip interaction software are a few of the broad
      categories of approaches that have been used in simulation-based assessments. The
      purpose of this article is to present a focused review of 3 sensor-enabled
      simulations that are currently being used for patient-centered assessments of
      clinical palpation skills. The first part of this article provides a review of
      technology components, capabilities, and metrics. The second part provides a
      detailed discussion regarding validity evidence and implications using the
      Standards for Educational and Psychological Testing as an organizational and
      evaluative framework. Special considerations are given to content domain and
      creation of clinical scenarios from a developer's perspective. The broader
      relationship of this work to the science of touch is also considered. 

PMID- 24084307
TI  - Evaluation of medical simulations.
AB  - Simulations hold great promise for medical education, but not all simulations are
      effective, and reviews of simulation-based medical education research indicate
      that most evaluations of the effectiveness of medical simulations have not been
      of sufficient technical quality to produce trustworthy results. This article
      discusses issues associated with the technical quality of evaluations and methods
      for achieving it in evaluations of the effectiveness of medical simulations. It
      begins with a discussion of the criteria for technical quality, and then
      discusses measures available for evaluating medical simulation, approaches to
      scoring simulation performance, and methodological approaches. It concludes with
      a summary and discussion of future directions in methods and technology for
      evaluating medical simulations. 

PMID- 24084308
TI  - Prevention of surgical skill decay.
AB  - The U.S. military medical community spends a great deal of time and resources
      training its personnel to provide them with the knowledge and skills necessary to
      perform life-saving tasks, both on the battlefield and at home. However,
      personnel may fail to retain specialized knowledge and skills if they are not
      applied during the typical periods of nonuse within the military deployment
      cycle, and retention of critical knowledge and skills is crucial to the
      successful care of warfighters. For example, we researched the skill and
      knowledge loss associated with specialized surgical skills such as those required
      to perform laparoscopic surgery (LS) procedures. These skills are subject to
      decay when military surgeons perform combat casualty care during their deployment
      instead of LS. This article describes our preliminary research identifying
      critical LS skills, as well as their acquisition and decay rates. It introduces
      models that identify critical skills related to laparoscopy, and proposes
      objective metrics for measuring these critical skills. This research will provide
      insight into best practices for (1) training skills that are durable and
      resistant to skill decay, (2) assessing these skills over time, and (3)
      introducing effective refresher training at appropriate intervals to maintain
      skill proficiency. 

PMID- 24084309
TI  - Effects of simulation-based practice on focused assessment with sonography for
      trauma (FAST) window identification, acquisition, and diagnosis.
AB  - We compared the effects of simulator-based virtual ultrasound scanning practice
      with classroom-based ultrasound scanning practice on participants' knowledge of
      focused assessment with sonography for trauma (FAST) window quadrants and
      interpretation, and on participants' performance on live patient FAST
      examinations. Novices with little or no ultrasound training experience received
      simulation-based practice (n = 24) or classroom-based practice (n = 24).
      Participants who received simulation-based practice scored significantly higher
      on interpreting static images of FAST windows. On live patient examinations where
      participants scanned the right upper quadrant (RUQ), left upper quadrant (LUQ),
      and suprapubic quadrant of a normal patient and an ascites-positive patient, the
      classroom-based practice condition had a shorter scan time for the LUQ and a
      higher number of participants attaining high-quality window on the RUQ (normal
      patient only) and suprapubic quadrant (positive patient only) and correct window
      interpretation on the LUQ (normal patient only). Overall, classroom-based
      practice appeared to promote physical acquisition skills and simulator-based
      practice appeared to promote window interpretation skills. Accurate window
      interpretation is critical to identification of blunt abdominal trauma injuries.
      The simulator used (SonoSimulator) appears promising as a training tool to
      increase probe time and to increase exposure to FAST windows reflecting various
      anatomy and disease states. 

PMID- 24084310
TI  - Adaptive and perceptual learning technologies in medical education and training.
AB  - Recent advances in the learning sciences offer remarkable potential to improve
      medical education and maximize the benefits of emerging medical technologies.
      This article describes 2 major innovation areas in the learning sciences that
      apply to simulation and other aspects of medical learning: Perceptual learning
      (PL) and adaptive learning technologies. PL technology offers, for the first
      time, systematic, computer-based methods for teaching pattern recognition,
      structural intuition, transfer, and fluency. Synergistic with PL are new adaptive
      learning technologies that optimize learning for each individual, embed objective
      assessment, and implement mastery criteria. The author describes the Adaptive
      Response-Time-based Sequencing (ARTS) system, which uses each learner's accuracy
      and speed in interactive learning to guide spacing, sequencing, and mastery. In
      recent efforts, these new technologies have been applied in medical learning
      contexts, including adaptive learning modules for initial medical diagnosis and
      perceptual/adaptive learning modules (PALMs) in dermatology, histology, and
      radiology. Results of all these efforts indicate the remarkable potential of
      perceptual and adaptive learning technologies, individually and in combination,
      to improve learning in a variety of medical domains. 

PMID- 24084311
TI  - Evidence-centered design for simulation-based assessment.
AB  - Simulations provide opportunities for people to learn and to develop skills for
      situations that are expensive, time-consuming, or dangerous. Careful design can
      support their learning by tailoring the features of situations to their levels of
      skill, allowing repeated attempts, and providing timely feedback. The same
      environments provide opportunities for assessing people's capabilities to act in
      these situations. This article describes an assessment design framework that can
      help projects develop effective simulation-based assessments. It reviews the
      rationale and terminology of the "evidence-centered" assessment design framework,
      discusses how it aligns with the principles of simulation design, and illustrates
      ideas with examples from engineering and medicine. Advice is offered for
      designing a new simulation-based assessment and for adapting an existing
      simulation system for assessment purposes. 

PMID- 24084312
TI  - Potential applications of latent variable modeling for the psychometrics of
      medical simulation.
AB  - Use of simulation-based assessments and training has become increasingly
      widespread in medicine. It is recognized that simulations can yield a wealth of
      real-time information about the trainee or examinee's performance, from which
      inferences about proficiency can potentially be drawn. However, for the
      inferences to be useful, psychometric evaluation should be conducted and validity
      evidence amassed. Traditionally, educational and psychological measurement has
      relied on psychometric models that are static, unidimensional, and based on
      observed scores. In this article, it is argued that modern psychometric models
      that are dynamic, multidimensional, and based on latent variables may be useful
      for evaluating medical simulations. It is also argued that modern computational
      methods based on Bayesian statistics may provide the technical foundation.
      Several examples are given and issues for further research are discussed. 

PMID- 24084313
TI  - Use of the assessment-diagnosis-treatment-outcomes model to improve patient care.
AB  - OBJECTIVES: The primary aim of this review was to compare and contrast the
      principles of the Assessment-Diagnosis-Treatment-Outcomes (ADTO) model with
      clinical prediction rules, shared decision making, and practice guidelines and
      provide a framework for validating medical simulations. METHODS: Comparing and
      contrasting the various methods and tools used by the clinical community and
      patients to help make informed decisions regarding health care options. RESULTS:
      The ADTO model provides an excellent theoretical framework to analyze and
      conceptualize the interrelationships between clinicians and patients as they go
      through the process of determining best practices. However, the ADTO model may be
      too comprehensive to implement within any given clinical prediction rule or
      hypothetical-construct-oriented medical simulation, at least at this point in the
      development of these fields. CONCLUSIONS: The way forward for developing
      substantive medical simulations that will tie together complex constructs is to
      start at the beginning and plan to make small steps as a basis for establishing
      the infrastructure that will lead to a giant leap for mankind.

PMID- 24084314
TI  - Activities on Facebook reveal the depressive state of users.
AB  - BACKGROUND: As online social media have become prominent, much effort has been
      spent on identifying users with depressive symptoms in order to aim at early
      diagnosis, treatment, and even prevention by using various online social media.
      In this paper, we focused on Facebook to discern any correlations between the
      platform's features and users' depressive symptoms. This work may be helpful in
      trying to reach and detect large numbers of depressed individuals more easily.
      OBJECTIVE: Our goal was to develop a Web application and identify depressive
      symptom-related features from users of Facebook, a popular social networking
      platform. METHODS: 55 Facebook users (male=40, female=15, mean age 24.43, SD
      3.90) were recruited through advertisement fliers distributed to students in a
      large university in Korea. Using EmotionDiary, the Facebook application we
      developed, we evaluated depressive symptoms using the Center for Epidemiological
      Studies-Depression (CES-D) scale. We also provided tips and facts about
      depression to participants and measured their responses using EmotionDiary. To
      identify the Facebook features related to depression, correlation analyses were
      performed between CES-D and participants' responses to tips and facts or Facebook
      social features. Last, we interviewed depressed participants (CES-D>=25) to
      assess their depressive symptoms by a psychiatrist. RESULTS: Facebook activities
      had predictive power in distinguishing depressed and nondepressed individuals.
      Participants' response to tips and facts, which can be explained by the number of
      app tips viewed and app points, had a positive correlation (P=.04 for both
      cases), whereas the number of friends and location tags had a negative
      correlation with the CES-D scale (P=.08 and P=.045 respectively). Furthermore, in
      finding group differences in Facebook social activities, app tips viewed and app
      points resulted in significant differences (P=.01 and P=.03 respectively) between
      probably depressed and nondepressed individuals. CONCLUSIONS: Our results using
      EmotionDiary demonstrated that the more depressed one is, the more one will read
      tips and facts about depression. We also confirmed depressed individuals had
      significantly fewer interactions with others (eg, decreased number of friends and
      location tagging). Our app, EmotionDiary, can successfully evaluate depressive
      symptoms as well as provide useful tips and facts to users. These results open
      the door for examining Facebook activities to identify depressed individuals. We
      aim to conduct the experiment in multiple cultures as well.

PMID- 24084315
TI  - Reliability of corticomotor excitability in leg and thigh musculature at 14 and
      28 days.
AB  - CONTEXT: Alterations in corticomotor excitability are observed in a variety of
      patient populations, including the musculature surrounding the knee and ankle
      after joint injury. Active motor threshold (AMT) and motor-evoked-potential (MEP)
      amplitudes elicited through transcranial magnetic stimulation (TMS) are outcome
      measures used to assess corticomotor excitability and have been deemed reliable
      in upper-extremity musculature. However, there are few studies assessing the
      reliability of TMS measures in lower-extremity musculature. OBJECTIVE: To
      determine the intersession reliability of AMT and MEP amplitudes over 14 and 28 d
      in the quadriceps and fibularis longus (FL). DESIGN: Descriptive laboratory
      study. SETTING: University laboratory PARTICIPANTS: 20 able-bodied volunteers (10
      men, 10 women; 22.35 +/- 2.3 y, 1.71 +/- 0.11 m, 73.61 +/- 16.77 kg). MAIN
      OUTCOME MEASURES: AMT and MEP amplitudes were evaluated at 95%, 100%, 105%, 110%,
      120%, 130%, and 140% of AMT in the dominant and nondominant quadriceps and FL.
      Interclass correlation coefficients (ICCs) were used to assess reliability for
      absolute agreement and internal consistency between baseline and 2 follow-up
      sessions at 14 and 28 d postbaseline. Each ICC was fit with the best-fit straight
      line or parabola to smooth out noise in the observations and best determine if a
      pattern existed in determining the most reliable MEP value. RESULTS: All muscles
      yielded strong ICCs between baseline and both time points for AMT. MEPs in both
      the quadriceps and FL produced varying degrees of reliability, with the greatest
      reliability demonstrated on day 28 at 130% and 140% of AMT in the quadriceps and
      FL, respectively. The dominant FL muscle showed a significant pattern; as TMS
      intensity increased, MEP reliability increased. CONCLUSION: TMS can be used to
      reliably identify corticomotor alterations after therapeutic interventions, as
      well as monitor disease progression.

PMID- 24084316
TI  - On the association between nandrolone-mediated testosterone reduction during
      alcohol intoxication and attenuated voluntary alcohol intake in rats.
AB  - Human studies have indicated that the use of anabolic androgenic steroids may be
      associated with the abuse of alcohol and other drugs. Also, experimental animal
      research has indicated that chronic nandrolone administration subsequently
      increases voluntary alcohol drinking. The aim of our study was to test our
      hypothesis that alcohol-induced testosterone elevation, especially associated
      with stress conditions derived by nandrolone treatment, could be the underlying
      factor in causing increased alcohol drinking. Male alcohol-preferring AA and low
      drinking Wistar rats were randomly divided into control and nandrolone decanoate
      treated (15 mg/kg for 14 days) groups. Basal serum testosterone and
      corticosterone were determined before the first nandrolone treatment, after 7
      days of treatment, and after an additional (7-day) washout period, during which
      also the acute effect of alcohol (1.5 g/kg) on steroid hormones was determined.
      Hereafter followed a (5-week) voluntary alcohol consumption period, during the
      last 2 weeks of which the rats were treated again with nandrolone. Both normal
      and reversed dark- vs. light-cycle experimental designs were used. Contrary to
      our hypothesis, nandrolone treatment decreased voluntary alcohol consumption in
      both AA and Wistar rats. Also, instead of stress causation, elevated basal
      testosterone and lowered basal corticosterone levels were observed after
      nandrolone treatment in both AA rats and Wistars. During acute alcohol
      intoxication the frequency of testosterone decreases was higher in the nandrolone
      treated groups compared with control AA and Wistar rats. Present data support the
      hypothesis that nandrolone-treatment mediated attenuation of alcohol intake in
      both AA and Wistar rats may be the result of negative reinforcement caused by
      alcohol-mediated testosterone reduction.

PMID- 24084317
TI  - Enhancement and inhibition of apomorphine-induced sensitization in rats exposed
      to immobilization stress: relationship with adaptation to stress.
AB  - Stress increases vulnerability to addiction while drugs of abuse impair coping
      responses and pre-dispose to depression. Pre-clinical research shows that stress
      exposure augments locomotor sensitization effects of drugs of abuse and impairs
      behavioral tolerance to repeated stress. The present study investigates
      relationship between behavioral tolerance to repeated immobilization stress and
      apomorphine-induced sensitization. Apomorphine was injected either before
      exposure or after the termination of immobilization, daily for 5 days, to monitor
      drug-induced behavioral sensitization and tolerance in immobilization stress
      induced anorexia. We find that apomorphine-induced sensitization is enhanced and
      tolerance to repeated immobilization is impaired if the drug is administered
      before exposure to stress episode. Conversely, apomorphine-induced sensitization
      is inhibited and adaptation to stress is facilitated if the drug is administered
      after the termination of stress episode. It shows that apomorphine, if
      experienced during stress, produces greater sensitization and impairs stress
      tolerance. Conversely, sensitization effects of apomorphine are blocked and
      tolerance to stress is facilitated in animals receiving drug after the
      termination of stress episode. It is suggested that additive effects of stress
      and apomorphine on mesocorticolimbic dopamine neurotransmission and 5-HT-1A
      influences on dopamine neurotransmission may have a role in the modulation of
      apomorphine sensitization and tolerance to repeated immobilization stress. The
      results may help develop potential pharmacotherapies when substance
      abuse/dependence disorder and depression occur together.

PMID- 24084318
TI  - Opioid receptor types involved in the development of nicotine physical dependence
      in an invertebrate (Planaria) model.
AB  - Recent data suggest that opioid receptors are involved in the development of
      nicotine physical dependence in mammals. Evidence in support of a similar
      involvement in an invertebrate (Planaria) is presented using the selective opioid
      receptor antagonist naloxone, and the more receptor subtype-selective antagonists
      CTAP (D-Phe-Cys-Tyr-D-Trp-Arg-Thr-Pen-Thr-NH2) (MU, MOR), naltrindole (delta,
      DOR), and nor-BNI (norbinaltorphimine) (kappa, KOR). Induction of physical
      dependence was achieved by 60-min pre-exposure of planarians to nicotine and was
      quantified by abstinence-induced withdrawal (reduction in spontaneous locomotor
      activity). Known MOR and DOR subtype-selective opioid receptor antagonists
      attenuated the withdrawal, as did the non-selective antagonist naloxone, but a
      KOR subtype-selective antagonist did not. An involvement of MOR and DOR, but not
      KOR, in the development of nicotine physical dependence or in abstinence-induced
      withdrawal was thus demonstrated in a sensitive and facile invertebrate model. 

PMID- 24084320
TI  - Four new C18-diterpenoid alkaloids with analgesic activity from Aconitum
      weixiense.
AB  - Four new C18-diterpenoid alkaloids, weisaconitines A-D (1-4), were isolated from
      Aconitum weixiense. Based on extensive UV, IR, MS, 1D and 2D NMR analyses, their
      structures were elucidated as 8-O-ethyldolaconine (1), 4-demethylgenicunine B
      (2), 14-oxoaconosine (3), and 8-O-ethylaconosine (4). The analgesic activity of
      compound 4 was studied with CH3COOH-induced writhing model in mice. Compound 4
      showed writhing inhibitions of 24% (50 mg/kg), 26% (100 mg/kg) and 34% (200
      mg/kg), respectively, as compared to the reference drug aspirin (63%) at a dose
      of 200 mg/kg.

PMID- 24084319
TI  - Anti-androgenic activity of hydroxyxanthones in prostate cancer LNCaP cells.
AB  - Anti-androgens are used to treat prostate cancer. Here, we report that
      hydroxyxanthones from a plant extract act as anti-androgens in androgen receptor
      (AR)-positive prostate cancer LNCaP cells. Anti-androgenic activity of the
      ethanol extract from Garcinia subelliptica was observed in a luciferase assay
      using LNCaP/MMTV cells with a stably integrated mouse mammary tumor virus (MMTV)
      promoter. HPLC-based activity profiling followed by a chemical library-based
      assay strategy enabled the rapid identification of several active principles
      bearing a xanthone core substituted with hydroxyl and isoprenyl groups. Among the
      active compounds, 2-(1,1-dimethyl-allyl)-1,4,5,6-tetrahydroxyxanthone
      (subelliptenone F) was identified as a potent inhibitor of AR transcriptional
      activity. The structure-activity relationship of some substituents on the
      xanthone core was also determined using the chemical library-based bioassay. A
      quantitative RT-PCR analysis revealed that treatment with the compound resulted
      in a significant reduction in AR-induced gene (KLK3) expression. Hydroxyxanthone
      may be a possible candidate for the development of a new anti-androgenic
      molecule. 

PMID- 24084321
TI  - The effects of cooperation between orthopaedic surgeons and microbiologists on
      the effectiveness of diagnosis and treatment of septic hip joint loosening.
AB  - BACKGROUND: The objective of this study is to compare the results of
      microbiological examinations of two types of materials: specimens collected
      intraoperationally upon removal of prostheses following septic loosening and
      cultures from sonicated implants. The study was the effect of collaboration
      between the Clinic of Orthopedics of A. Gruca Hospital in Otwock and the
      Department of Microbiology in Lublin. MATERIAL AND METHODS: The study population
      consisted of 24 patients aged 39 to 84 years, average of 68 years, undergoing
      surgeries at the Department of Bone and Joint Inflammation, Clinic of Orthopedics
      of A. Gruca Hospital in Otwock in years 2010-2011. All patients were qualified
      for surgical treatment consisting of removal of hip prosthesis due to
      inflammation. Sixty percent of the group were women, while the remaining forty
      percent were men. The methodology of the study was based on intraoperational
      collection of material for microbiological examinations at the Department of
      Microbiology of A. Gruca Hospital. The study material was collected from 3
      locations: femoral shank, hip acetabulum and gluteal muscle. Explanted implants
      were placed in sterile containers, frozen at -20 degrees C and transported to the
      Department of Microbiology in Lublin. There, the implants were sonicated.
      RESULTS: The obtained results were consistent in both groups in 37% of cases. In
      9 patients (37%), standard cultures were negative while the cultures of sonicated
      material were positive. In 16 patients (67%), the spectrum of perioperative and
      sequential antibiotic therapy included flora cultured by standard methods as well
      as flora obtained from sonicated implant cultures. In the remaining patients,
      cultures obtained from sonicated material were resistant to antibiotics used.
      CONCLUSIONS: Cultures of sonicated implant materials increase the chance for
      identification of microbes responsible for inflammation. Limitations of the
      method include the requirement to either examine the implant shortly after
      removal or freeze the implant in order to prevent secondary infections of the
      material.

PMID- 24084322
TI  - Inadvertent placement of a glaucoma tube into the graft-host interface of an eye
      with previous Descemet stripping automated endothelial keratoplasty.
AB  - PURPOSE: The aim of this study was to report the inadvertent insertion of a
      glaucoma tube into the graft-host interface in a patient with previous Descemet
      stripping automated endothelial keratoplasty (DSAEK). METHODS: This is a
      retrospective case report. RESULTS: A 56-year-old aniridic woman with a history
      of multiple failed penetrating keratoplasties (PKPs) and glaucoma underwent DSAEK
      under failed PKP of her left eye at our institution. After undergoing a
      subsequent glaucoma tube placement by an outside glaucoma specialist, the tube
      was identified in the DSAEK-PKP interface. The tube was successfully repositioned
      at the time of repeat PKP with placement of a Boston type I keratoprosthesis.
      CONCLUSIONS: Inadvertent insertion of a glaucoma tube into the DSAEK interface
      may result in ocular morbidity in patients with previous DSAEK surgery.

PMID- 24084323
TI  - Greater omentum folding in the open surgical placement of peritoneal dialysis
      catheters: a randomized controlled study and systemic review.
AB  - BACKGROUND: Mechanical catheter dysfunction caused by omentum entrapment remains
      a major complication of peritoneal dialysis (PD) therapy. The purpose of this
      study was to determine the outcomes of omentum folding at the time of primary
      open catheter insertion. METHODS: From March 2008 to December 2012, a total of 67
      PD subjects were enrolled in the study and randomly assigned to receive either
      regular open insertion (ROI group, n = 33) or open insertion with omentum folding
      (OIOF group, n = 34). The primary outcome was defined as PD catheter tip
      migration with dysfunction. A systematic review was performed to analyze the
      outcomes of omentum management in PD catheter implantation, based on published
      data from 1990 to 2013. RESULTS: There was no statistical difference in baseline
      patient characteristics between the ROI and OIOF groups. Nine (27.3%) patients in
      the ROI group presented with catheter malposition in the late stage (>60 days) of
      the study, significantly more than in the OIOF group (two; 5.9%) (P = 0.049).
      Significant differences in catheter survival rate between the two groups were
      observed in the late stage (P = 0.030) and over the entire study period (P =
      0.028). A higher incidence of irreversible catheter dysfunction was shown in the
      ROI group (15.2%), whereas none occurred in the OIOF group (P = 0.031). No
      statistical difference was determined in other catheter-related complications or
      patient survival rate. There were no statistical differences in peritoneal
      transport characteristics or dialysis adequacy between the two groups upon
      evaluation at 3, 6 and 12 months. Systemic review of current publications
      suggested that PD catheter placement with omentum management could lead to less
      irreversible catheter dysfunction and improved outcome of catheter survival.
      CONCLUSIONS: Our data suggest that omentum folding at the initial time of open
      catheter placement can significantly reduce the risk of catheter tip migration
      with dysfunction and improve the outcome of the PD technique.

PMID- 24084324
TI  - Using linked administrative data to study periprocedural mortality in obesity and
      chronic kidney disease (CKD).
AB  - Both obesity and chronic kidney disease (CKD) are associated with adverse
      periprocedural outcomes, but it is unknown how these two common conditions
      interact to influence risk. We examined the feasibility of combining a new
      procedure-related, obesity-specific flag with administrative and laboratory data
      and assessed the joint association between obesity and CKD with mortality. Since
      2007, Alberta physicians may claim a fee supplement for performing eligible
      surgical and non-surgical procedures on patients with documented BMI >= 35
      kg/m(2). We linked this information to the Alberta Kidney Disease Network
      registry. Participants were classified into four mutually exclusive groups based
      on the presence/absence of both obesity (BMI >= 35 kg/m(2)) and CKD (eGFR < 60
      mL/min/1.73 m(2)). Mortality was assessed at 30 days following the index
      procedure. Of 393 659 participants, 9% were obese. Overall, 8% had obesity only,
      78% neither obesity nor CKD, 13% CKD only and 1% both obesity and CKD. Unadjusted
      risks of mortality at 30 days were 0.3, 0.4, 2.0 and 2.1%, respectively--but
      decreased to 0.1, 0.2, 0.3 and 0.3%, respectively, after adjustment for age, sex,
      socioeconomic status, procedure type and other comorbidities. Administrative data
      can be feasibly combined with disease registries to study obesity-related
      outcomes. Results from the linked dataset demonstrated face validity--subjects
      with both obesity and CKD were at increased risk of periprocedural mortality, and
      this was driven in part by differences in age and comorbidity.

PMID- 24084325
TI  - Hydroxyurea is associated with lower prevalence of albuminuria in adults with
      sickle cell disease.
AB  - BACKGROUND: Albuminuria is an early manifestation of sickle cell nephropathy.
      Prior small case series suggests benefit of hydroxyurea in reducing albuminuria,
      with a similar trend noted in pediatric studies. We aimed to comprehensively
      evaluate hydroxyurea use and prevalence of albuminuria in adult sickle cell
      patients. METHODS: We performed a cross-sectional study of 149 adult patients
      followed between 2000 and 2011 in a comprehensive sickle cell clinic. All
      patients were assessed for albuminuria either by direct measurement or by urinary
      chemical strip (dipstick) testing. Urinary albumin-to-creatinine ratios (UACRs)
      were available for 112 patients. Hydroxyurea exposure was defined as >=3 months
      of therapy before the assessment of albuminuria. Albuminuria was defined as
      either UACR >=30 mg/g or >=1+ proteinuria on two separate dipsticks. We
      constructed a multivariate logistic regression model to assess the association
      between hydroxyurea and albuminuria. RESULTS: The prevalence of albuminuria was
      lower among patients on hydroxyurea (34.7 versus 55.4%; P = 0.01) as was median
      albumin excretion (17.9 versus 40.5 mg/g; P = 0.04). In multivariate analysis,
      hydroxyurea was associated with a lower likelihood of albuminuria (odds ratio
      0.28, 95% CI: 0.11-0.75, P = 0.01), adjusting for age, angiotensin-converting
      enzyme inhibitor/angiotensin receptor blocker use, tricuspid regurgitant jet
      velocity, hypertension and acute chest syndrome. CONCLUSIONS: In our population
      of sickle cell patients, those using hydroxyurea were less than one-third as
      likely to exhibit albuminuria. Hydroxyurea use may prevent development of overt
      nephropathy or the progression of sickle cell disease nephropathy to end-stage
      renal disease, and its use for this indication merits further investigation.

PMID- 24084326
TI  - Assessment of arterial stiffness for clinical and epidemiological studies:
      methodological considerations for validation and entry into the European Renal
      and Cardiovascular Medicine registry.
AB  - Epidemiological studies have highlighted the role of arterial stiffness as a risk
      factor for development of cardiovascular (CV) diseases. Moreover, aortic
      stiffness has been shown to be a significant predictive factor of all-cause and
      CV mortality in different populations including patients with end-stage renal
      disease. Pulse-wave velocity (PWV) is the most widely used technique to assess
      arterial stiffness. Although PWV can be measured on any artery or between any
      arterial sites, only carotid-to-femoral PWV, representing stiffness of the aorta
      and iliofemoral axes, has been shown to have predictive value for morbidity and
      mortality. The several available commercial devices differ according to the type
      of signal (pressure, distension, flow) or by recording both sites simultaneously
      or using ECG synchronization. It is also possible to directly measure arterial
      diameter changes during the cardiac cycle and link them to local pulse-pressure
      changes, which provides the pressure-diameter relationship and stress-strain
      relationship if arterial wall thickness is also measured. These techniques are
      based on high-precision vascular echo tracking or magnetic resonance imaging and
      applanation tonometry. This paper summarizes the basic principles of arterial
      haemodynamics and various methodologies to assess stiffness and the latest
      consensus recommendations for clinical applications. 

PMID- 24084327
TI  - Therapeutic equivalence and pharmacokinetics of generic tacrolimus formulation in
      de novo kidney transplant patients.
AB  - BACKGROUND: There is a growing concern about the therapeutic equivalence of the
      generic tacrolimus formulation (GEN Tacrolimus) to the reference tacrolimus (REF
      Tacrolimus) in solid organ transplantation. METHODS: A prospective, randomized
      study of 126 de novo renal transplant patients was conducted to compare the
      efficacy, safety and pharmacokinetic (PK) profiles between GEN tacrolimus (n =
      63) and REF tacrolimus (n = 63). The PK of tacrolimus was evaluated on Day 10 and
      6 months under steady-state condition. Crossover study was carried out in 66
      patients at 6 months. RESULTS: On Day 10, 117 patients completed PK profiles (54
      GEN tacrolimus and 63 REF tacrolimus) and GEN tacrolimus showed comparable C(0)
      (9.8 +/- 2.5 versus 9.7 +/- 3.0 ng/mL, P = 0.80) but significantly higher dose
      normalized C(max) (309.1 +/- 191.9 versus 192.5 +/- 95.2 ng/mL/mg/kg, P < 0.001).
      The dose-normalized AUC(0-12) tended to be higher in the GEN tacrolimus than in
      the REF tacrolimus group (1513.4 +/- 935.4 versus 1262.5 +/- 593.5 ng.h/mL/mg/kg,
      P = 0.084). Because of this early and high C(max) with a rapid decline in GEN
      tacrolimus concentration, the trough concentration was maintained lower than that
      of REF tacrolimus. At 6 months, GEN tacrolimus showed equivalent dose-normalized
      AUC(0-12) (1882.2 +/- 935.6 versus 1718.1 +/- 946.3 ng.h/mL/mg/kg, P = 0.429) but
      still higher dose-normalized C(max) (346.3 +/- 184.4 versus 273.2 +/- 148.9
      ng/mL/mg/kg, P = 0.056), despite a reduced trough concentration (5.7 +/- 1.6
      versus 6.9 +/- 2.2 ng/mL, P = 0.004). PK profiles evaluated at 9 months showed
      that generic substitution also resulted in an 'early and high C(max)'. Efficacy
      and safety data were comparable over the 9-month study period. CONCLUSIONS:
      Therapeutic equivalence and the PK of GEN tacrolimus should be evaluated in
      patients undergoing de novo renal transplantation.

PMID- 24084328
TI  - HLA-A2, HLA-B44 and HLA-DR15 are associated with lower risk of BK viremia.
AB  - BACKGROUND: Human leucocyte antigens (HLAs) modulate immunity to polyomavirus BK
      (BKV). Identification of HLAs that alter the course of infection will facilitate
      risk stratification, and customization of pre-emptive intervention strategies.
      METHODS: We performed a retrospective cohort study with 998 kidney transplant
      patients with BKV infection status confirmed by polymerase chain reaction (PCR).
      Clinical parameters and donor-recipient matching for specific HLAs were examined
      in relation to occurrence of viremia. An emphasis was placed on donor-recipient
      matching rather than the actual frequency of specific HLA-alleles, since a
      successful immune response requires sharing of HLAs between a virus-infected
      target cell and the anti-viral effector cell. RESULTS: Using multivariate
      statistics, low risk of BK viremia was associated with matching of HLA-A2 [hazard
      ratio (HR) 0.51, 95% confidence interval (CI) 0.28-0.85], HLA-B44 (HR 0.31, 95%
      CI 0.076-0.85) and HLA-DR15 (HR 0.35, 95% CI 0.084-0.93) (P < 0.05), whereas high
      risk of viremia was associated with male gender (HR 2.38, 95% CI 1.46-4.09, P <
      0.001). CONCLUSIONS: HLAs that associated with a lower predisposition to the
      development of BK viremia have been identified. Evaluation of donor-recipient
      mismatching for these HLAs could potentially be used to (i) fine tune virus
      screening strategies for BKV in individual patients and (ii) facilitate discovery
      of major histocompatibility complex (MHC) class I and II binding peptides that
      can elicit clinically meaningful BKV-specific immunity.

PMID- 24084329
TI  - Autocrine and paracrine modulation of microRNA-155 expression by globular
      adiponectin in RAW 264.7 macrophages: involvement of MAPK/NF-kappaB pathway.
AB  - Adiponectin, a hormone produced from adipose tissue, regulates various biological
      responses, including inflammation and many metabolic processes. MicroRNAs control
      expression of diverse target genes and various physiological responses. Many of
      these responses are commonly regulated by adiponectin. However, effects of
      adiponectin on microRNAs regulation are largely unknown. Herein we demonstrated
      that globular adiponectin induces increase in miR-155 expression, which plays an
      important role in inflammatory response, in RAW 264.7 macrophages. We further
      showed that this effect was modulated by and MAPK/NF-kappaB dependent mechanisms.
      These results suggest that miR-155 would be a novel promising target mediating
      adiponectin-induced various biological responses.

PMID- 24084331
TI  - Identification of a soluble isoform of human IL-17RA generated by alternative
      splicing.
AB  - IL-17RA, a member of the interleukin (IL)-17 receptor family, is a single
      membrane-spanning protein that ubiquitously expressed on the cell surface. IL
      17RA transduces IL-17A, IL-17F, and IL-17A/F heterodimer-mediated signals by
      forming a complex with IL-17RC, and also signals the IL-17E (also known as IL-25)
      response in combination with IL-17RB (also known as IL-25R). Previously, soluble
      isoforms of human IL-17RC and IL-17RB have been reported, but the existence of a
      soluble isoform of human IL-17RA has remained unclear. Here, we report the
      identification of a soluble isoform of human IL-17RA at the mRNA and protein
      levels. Reverse transcribed PCR experiments showed that the IL-17RA variant is
      generated by spliced out of exon 11 encoding the transmembrane region in a
      variety of human tissues. The soluble IL-17RA isoform was detected in the culture
      media of human cell lines by Western blotting. The existence of the soluble IL
      17RA isoform sheds new light on the regulation of IL-17RA mediated responses. 

PMID- 24084330
TI  - Sustained elevation of serum interleukin-18 and its association with
      hemophagocytic lymphohistiocytosis in XIAP deficiency.
AB  - X-linked lymphoproliferative syndrome (XLP) is a rare primary immunodeficiency
      characterized by increased vulnerability to Epstein-Barr virus infection. XLP
      type 1 is caused by mutations in SH2D1A, whereas X-linked inhibitor of apoptosis
      (XIAP) encoded by XIAP/BIRC4 is mutated in XLP type 2. In XIAP deficiency,
      hemophagocytic lymphohistiocytosis (HLH) occurs more frequently and recurrence is
      common. However, the underlying mechanisms remain mostly unknown. We describe the
      characteristics of the cytokine profiles of serum samples from 10 XIAP-deficient
      patients. The concentration of interleukin (IL)-18 was strikingly elevated in the
      patients presented with HLH, and remained high after the recovery from HLH
      although levels of other pro-inflammatory cytokines approached the normal range.
      Longitudinal examination of two patients demonstrated marked exacerbation of IL
      18 levels during every occasion of HLH. These findings may suggest the
      association between HLH susceptibility and high serum IL-18 levels in XIAP
      deficiency. 

PMID- 24084332
TI  - The role of macrophages in obstructive airways disease: chronic obstructive
      pulmonary disease and asthma.
AB  - Macrophages are a major cellular component of the innate immune system, and play
      an important role in the recognition of microbes, particulates, and immunogens
      and to the regulation of inflammatory responses. In the lung, macrophages react
      with soluble proteins that bind microbial products in order to remove pathogens
      and particles and to maintain the sterility of the airway tract. Chronic
      obstructive pulmonary disease and asthma are both obstructive airway diseases
      that involve chronic inflammation of the respiratory tract which contributes to
      disease progression. In the case of COPD, there is increasing evidence that lung
      macrophages orchestrate inflammation through the release of chemokines that
      attract neutrophils, monocytes and T cells and the release of several proteases.
      On the other hand, in asthma, it seems that alveolar macrophages are
      inappropriately activated and are implicated in the development and progression
      of the disease. In this review we summarize the current basic and clinical
      research studies which highlight the role of macrophages in asthma and COPD. 

PMID- 24084333
TI  - Elastic modulus and collagen organization of the rabbit cornea: epithelium to
      endothelium.
AB  - The rabbit is commonly used to evaluate new corneal prosthetics and study corneal
      wound healing. Knowledge of the stiffness of the rabbit cornea would better
      inform the design and fabrication of keratoprosthetics and substrates with
      relevant mechanical properties for in vitro investigations of corneal cellular
      behavior. This study determined the elastic modulus of the rabbit corneal
      epithelium, anterior basement membrane (ABM), anterior and posterior stroma,
      Descemet's membrane (DM) and endothelium using atomic force microscopy (AFM). In
      addition, three-dimensional collagen fiber organization of the rabbit cornea was
      determined using nonlinear optical high-resolution macroscopy. The elastic
      modulus as determined by AFM for each corneal layer was: epithelium, 0.57 +/-
      0.29 kPa (mean +/- SD); ABM, 4.5 +/- 1.2 kPa, anterior stroma, 1.1 +/- 0.6 kPa;
      posterior stroma, 0.38 +/- 0.22 kPa; DM, 11.7 +/- 7.4 kPa; and endothelium, 4.1
      +/- 1.7 kPa. The biophysical properties, including the elastic modulus, are
      unique for each layer of the rabbit cornea and are dramatically softer in
      comparison to the corresponding regions of the human cornea. Collagen fiber
      organization is also dramatically different between the two species, with
      markedly less intertwining observed in the rabbit vs. human cornea. Given that
      the substratum stiffness considerably alters the corneal cell behavior,
      keratoprosthetics that incorporate mechanical properties simulating the native
      human cornea may not elicit optimal cellular performance in rabbit corneas that
      have dramatically different elastic moduli. These data should allow for the
      design of substrates that better mimic the biomechanical properties of the
      corneal cellular environment.

PMID- 24084334
TI  - Ultrasound-assisted extraction and purification of schisandrin B from Schisandra
      chinensis (Turcz.) Baill seeds: optimization by response surface methodology.
AB  - The objective of this study is to develop a process consisting of ultrasonic
      assisted extraction, silica-gel column chromatography and crystallization to
      optimize pilot scale recovery of schisandrin B (SAB) from Schisandra chinensis
      seeds. The effects of five independent variables including liquid-solid ratio,
      ethanol concentration, ultrasonic power, extraction time, and temperature on the
      SAB yield were evaluated with fractional factorial design (FFD). The FFD results
      showed that the ethanol concentration was the only significant factor for the
      yield of SAB. Then, with the liquid-solid ratio 5 (mL/g) and ultrasonic power 600
      W, the other three parameters were further optimized by means of response surface
      methodology (RSM). The RSM results revealed that the optimal conditions consisted
      of 95% ethanol, 60  degrees C and 70 min. The average experimental SAB yield
      under the optimum conditions was found to be 5.80 mg/g, which was consistent with
      the predicted value of 5.83 mg/g. Subsequently, a silica gel chromatographic
      process was used to prepare the SAB-enriched extract with petroleum ether/acetone
      (95:5, v/v) as eluents. After final crystallization, 1.46 g of SAB with the
      purity of 99.4% and the overall recovery of 57.1% was obtained from 400 g seeds
      powder. This method provides an efficient and low-cost way for SAB purification
      for pharmaceutical industrial applications.

PMID- 24084335
TI  - Characterization of opioid activities of endomorphin analogs with C-terminal
      amide to hydrazide conversion.
AB  - Previously, we have synthesized an endomorphin-2 (EM-2) analog with C-terminal
      amide to hydrazide conversion, exhibiting slightly lower MU-affinity than EM-2.
      In the present study, the influence of C-terminal amide group to hydrazide
      conversion on the in vitro and in vivo opioid activities of EMs was evaluated.
      Our results demonstrated that C-terminal amide to hydrazide conversion of EMs did
      not markedly change their MU-opioid receptor binding affinities. Nevertheless, EM
      2-NHNH2 decreased guinea pig ileum (GPI) and mouse vas deferens (MVD) potencies
      by about 10- and 5-fold compared to the parent compound, respectively. It is
      noteworthy that EM-1-NHNH2 exhibited the highest antinociception after
      intracerebroventricular (i.c.v.) injection, about 1.5-fold more potent than EM-1,
      but with moderate colonic contractile and expulsive effects, comparable with EM
      1. Additionally, though EM-2-NHNH2 showed a slightly lower antinociceptive effect
      than EM-2, at higher doses (i.c.v., 1.5 and 5 nmol/mouse) the inhibitory effects
      of colonic propulsion were significantly attenuated, which would be helpful in
      the development of suitable MU-opioid therapeutics, but without some undesirable
      side effects. Therefore, the present results gave the evidence that C-terminal
      amide to hydrazide conversion of EMs may play an important role in the regulation
      of opioid activities.

PMID- 24084336
TI  - Progressive chronic kidney disease and dual inhibition of the renin-angiotensin
      aldosterone system.

PMID- 24084337
TI  - Insidious reintroduction of wild poliovirus into Israel, 2013.
AB  - Israel was certified as polio-free country in June 2002, along with the rest of
      the World Health Organization European Region. Some 11 years later, wild-type
      polio virus 1 (WPV1) was isolated initially from routine sewage samples collected
      between 7 and 13 April 2013 in two cities in the Southern district. WPV1-specific
      analysis of samples indicated WPV1 introduction into that area in early February
      2013. National supplementary immunisation with oral polio vaccine has been
      ongoing since August 2013.

PMID- 24084338
TI  - Stability of Middle East respiratory syndrome coronavirus (MERS-CoV) under
      different environmental conditions.
AB  - The stability of Middle East respiratory syndrome coronavirus (MERS-CoV) was
      determined at 20 degrees C--40% relative humidity (RH); 30 degrees C--30% RH and
      30 degrees C--80% RH. MERS-CoV was more stable at low temperature/low humidity
      conditions and could still be recovered after 48 hours. During aerosolisation of
      MERS-CoV, no decrease in stability was observed at 20 degrees C--40% RH. These
      data suggest the potential of MERS-CoV to be transmitted via contact or fomite
      transmission due to prolonged environmental presence.

PMID- 24084339
TI  - Whole genome sequencing and phylogenetic analysis of West Nile virus lineage 1
      and lineage 2 from human cases of infection, Italy, August 2013.
AB  - A human outbreak of West Nile virus (WNV) infection caused by WNV lineage 2 is
      ongoing in northern Italy. Analysis of six WNV genome sequences obtained from
      clinical specimens demonstrated similarities with strains circulating in central
      Europe and Greece and the presence of unique amino acid changes that identify a
      new viral strain. In addition, WNV lineage 1 Livenza, responsible for a large
      outbreak in north-eastern Italy in 2012, was fully sequenced from a blood donor
      during this 2013 outbreak.

PMID- 24084340
TI  - Pertussis immunisation and control in England and Wales, 1957 to 2012: a
      historical review.
AB  - This review summarises the epidemiology and control of pertussis in England and
      Wales since the introduction of routine immunisation and considers the
      implications for future control. Routine infant immunisation with a whole-cell
      pertussis (wP) vaccine was introduced in 1957 and had a marked impact on the
      overall disease burden. Following a fall in vaccine coverage during the 1970s and
      80s linked to a safety scare with wP vaccine, there was an extended period of
      high coverage and pertussis incidence fell dramatically. Incidence continued to
      decrease with the introduction of an acellular pertussis vaccine in the pre
      school booster in November 2001 and in the primary United Kingdom (UK) schedule
      in September 2004 but has increased since July 2011. In response to a high rate
      of pertussis in infants, a temporary vaccination programme for pregnant women was
      introduced in October 2012. The key aim of the programme is to protect vulnerable
      infants from birth in the first months of life, before they can be fully
      protected by routine infant immunisation. A review of the UK adolescent
      immunisation programme is currently ongoing and the inclusion of a pertussis
      booster is being considered.

PMID- 24084343
TI  - Impact of portal vein thrombosis on the efficacy of endoscopic variceal band
      ligation.
AB  - BACKGROUND: Influence of portal vein thrombosis on efficacy of endoscopic
      variceal banding in patients with cirrhosis or extrahepatic portal vein
      obstruction has never been evaluated. Aim of the study was to assess influence of
      thrombosis on rate and time to eradication in cirrhosis and extrahepatic portal
      vein obstruction undergoing banding, compared to cirrhotic patients without
      thrombosis. METHODS: Retrospective analysis of 235 consecutive patients (192 with
      cirrhosis without thrombosis, 22 cirrhosis and thrombosis and 21 extrahepatic
      portal vein obstruction) who underwent banding. Banding was performed every 2-3
      weeks until eradication; endoscopic follow-up was performed at 1, 3, 6 months,
      then annually. RESULTS: Eradication was achieved in 233 patients. Median time to
      eradication in cirrhotic patients with portal vein thrombosis vs. cirrhotic
      patients without thrombosis was 50.9 days (12-440) vs. 43.4 days (13-489.4); log
      rank: 0.04; patients with extrahepatic portal vein obstruction vs. cirrhotic
      patients without thrombosis 63.9 days (31-321.6) vs. 43.4 days (13.0-489.4); log
      rank: 0.008. Thrombosis was shown to be the only risk factor for longer time to
      eradication. CONCLUSIONS: Portal vein thrombosis per se appears to be the cause
      of a longer time to achieve eradication of varices but, once eradication is
      achieved, it does not influence their recurrence.

PMID- 24084344
TI  - Cytogenetic damage in Turkish coke oven workers exposed to polycyclic aromatic
      hydrocarbons: Association with CYP1A1, CYP1B1, EPHX1, GSTM1, GSTT1, and GSTP1
      gene polymorphisms.
AB  - The aim of this study was to determine the frequencies of chromosomal aberrations
      (CA) and cytochalasin-blocked micronuclei (CBMN) in peripheral blood lymphocytes
      from Turkish coke oven workers and the influence of CYP1A1, CYP1B1, EPHX1, GSTM1,
      GSTT1, and GSTP1 gene polymorphisms on these biomarkers. Cytogenetic analysis
      showed that occupational exposure significantly increased the CA and CBMN
      frequencies. Gene polymorphisms, on the other hand, did not affect CA or CBMN in
      either exposed or control subjects. However, due to the limited sample size, our
      findings need to be verified in future studies with a larger sample.

PMID- 24084345
TI  - Indoor PM1, PM2.5, PM10 and outdoor PM2.5 concentrations in primary schools in
      Sari, Iran.
AB  - This study was carried out to determine the distribution of particles in
      classrooms in primary schools located in the centre of the city of Sari, Iran and
      identify the relationship between indoor classroom particle levels and outdoor
      PM2.5 concentrations. Outdoor PM2.5 and indoor PM1, PM2.5, and PM10 were
      monitored using a real-time Micro Dust Pro monitor and a GRIMM monitor,
      respectively. Both monitors were calibrated by gravimetric method using filters.
      The Kolmogorov-Smirnov test showed that all indoor and outdoor data fitted normal
      distribution. Mean indoor PM1, PM2.5, PM10 and outdoor PM2.5 concentrations for
      all of the classrooms were 17.6 MUg m(-3), 46.6 MUg m(-3), 400.9 MUg m(-3), and
      36.9 MUg m(-3), respectively. The highest levels of indoor and outdoor PM2.5
      concentrations were measured at the Shahed Boys School (69.1 MUg m(-3) and 115.8
      MUg m(-3), respectively). The Kazemi school had the lowest levels of indoor and
      outdoor PM2.5 (29.1 MUg m(-3) and 15.5 MUg m(-3), respectively). In schools
      located near both main and small roads, the association between indoor fine
      particle (PM2.5 and PM1) and outdoor PM2.5 levels was stronger than that between
      indoor PM10 and outdoor PM2.5 levels. Mean indoor PM2.5 and PM10 and outdoor
      PM2.5 were higher than the standards for PM2.5 and PM10, and there was a good
      correlation between indoor and outdoor fine particle concentrations.

PMID- 24084346
TI  - Side-by-side determination of workers' exposure to wood dust with IOM and open
      faced samplers.
AB  - Woodworkers' exposure to airborne particles is measured with different sampling
      techniques throughout the world. Due to a great number of exposure data obtained
      with different samplers, European countries have aimed over the last ten years to
      find a conversion factor for mass concentrations that would render these
      measurements comparable. Following the accepted EU standards and regulations, we
      replaced a 25 mm open-faced (OF) filter holder with an IOM head to determine
      woodworkers' exposure to inhalable dust and establish an IOM/OF sampler ratio
      that might serve as a reliable factor for converting the existing OF data to IOM
      dust mass concentration in the industrial environment. For this side-by-side
      sampling we used personal 25 mm OF (N=29) and IOM (N=29) sampling heads over
      eight working hours. The obtained IOM/OF ratios ranged between 0.7 and 2.3.
      However, mass concentrations obtained by IOM and OF samplers did not
      significantly differ. Our findings suggest that there is no need for conversion
      of the existing OF data for workers exposed to wood dust, provided that dust mass
      concentrations in the working environment range between 1 mg m-3 and 7 mg m-3.
      Future side-by-side measurements should also involve environments with low wood
      dust mass concentrations.

PMID- 24084347
TI  - Detection of thallium and uranium in well water and biological specimens of an
      eastern Croatian population.
AB  - Abstract Using inductively-coupled plasma mass spectrometry (ICP-MS), we measured
      the concentrations of thallium and uranium in local water resources from three
      villages (Celije, Draz, and Potnjani) in eastern Croatia, with the aim to
      determine if they were associated with the levels of these same elements in the
      serum, urine, and hair collected from the residents of this area. The exposure of
      the local population to thallium and uranium through drinking water was generally
      low. ICP-MS was capable of measuring the levels of both of the elements in almost
      all of the analysed samples. Although there were differences in the
      concentrations of both elements in water samples and biological specimens taken
      from the residents, they did not reach the maximum contaminant level in any of
      the four sample types studied. Although hair was previously reported as an
      excellent indicator of occupational and environmental exposure to various
      elements, our study did not confirm it as a reliable biological material for
      tracing thallium and uranium levels, mainly due to the very low concentrations of
      these elements, often well below the detection limit. However, our results have
      shown that the concentration of thallium and uranium in drinking water can be
      effectively traced in urine samples.

PMID- 24084348
TI  - Cadmium and lead in grey wolf liver samples: optimisation of a microwave-assisted
      digestion method.
AB  - A microwave-assisted digestion method for the determination of cadmium (Cd) and
      lead (Pb) by inductively coupled plasma mass spectrometry (ICP-MS) was optimised
      on certified reference material (CRM) (bovine liver, BCR-185R) and wolf liver
      samples. Different factors influencing digestion efficiency (temperature, time,
      composition of the digestion mixture, sample mass) were tested. Validation
      included linearity (up to 200 MUg L(-1) for Cd and Pb), detection (0.003 MUg L(
      1) for Cd and 0.035 MUg L(-1) for Pb), and quantification (0.008 MUg L(-1) for Cd
      and 0.081 MUg L(-1) for Pb) limits. Good agreement between measured and certified
      values was achieved in all conditions, with recoveries ranging from 94 % to 111 %
      for Cd and from 95 % to 105 % for Pb. The precision of the method, expressed as
      relative standard deviation, was up to 3 % for Cd and 8 % for Pb. The best
      digestion parameters (260  degrees C, 30 min, 1 mL HNO3+4 mL H2O, 0.1 g of CRM)
      based on accuracy and precision were applied on two wolf liver samples to
      evaluate the need for the predigestion step (freeze-drying) and appropriate mass
      of the sample. Freeze-drying improved precision and minimising the tissue mass to
      0.1 g reduced the matrix effect. Using these optimised digestion conditions, we
      determined Cd and Pb in 40 wolf livers collected in Croatia, and their medians
      (0.055 MUg g(-1) and 0.107 MUg g(-1), respectively) were in the range of
      previously reported data for the grey wolf.

PMID- 24084349
TI  - Effects of taurine against histomorphological and ultrastructural changes in the
      testes of mice exposed to aluminium chloride.
AB  - The aim of this study was to investigate the protective effects of taurine
      against histomorphological and ultrastructural changes in the testes of Swiss
      albino mice caused by acute in vivo exposure to AlCl3. Light microscopy revealed
      that a single intraperitoneal (i.p.) dose of AlCl3 (25 mg kg(-1) Al(3+)) was
      associated with sloughing, tubular atrophy, germ-cell degeneration, and foci of
      Leydig cell hyperplasia. In addition, transmission electron microscopy showed a
      destruction of inter-Sertoli cell tight junctions, apoptotic cell death of
      spermatogonia and primary spermatocytes, various types of abnormalities in
      spermatid morphology, accumulation of lipid droplets, reduction of the smooth
      endoplasmic reticulum (sER), and mitochondrial damage in Leydig cells. Taurine
      post-treatment at i.p. dose of 1 g kg(-1) diminished these changes and
      significantly reduced the number of affected tubules compared to Al-poisoned
      mice. This is the first study to evidence that taurine protects against
      pathological changes in the testicular tissue of Al-treated mice.

PMID- 24084350
TI  - Anticancer and antioxidant properties of terpinolene in rat brain cells.
AB  - Terpinolene (TPO) is a natural monoterpene present in essential oils of many
      aromatic plant species. Although various biological activities of TPO have been
      demonstrated, its neurotoxicity has never been explored. In this in vitro study
      we investigated TPO's antiproliferative and/or cytotoxic properties using the 3
      (4,5-dimethylthiazol-2-yl)-2,5 diphenyltetrazolium bromide (MTT) test, genotoxic
      damage potential using the single-cell gel electrophoresis (SCGE), and oxidative
      effects through total antioxidant capacity (TAC) and total oxidative stress (TOS)
      in cultured primary rat neurons and N2a neuroblastoma cells. Dose-dependent
      effects of TPO (at 10 mg L(-1), 25 mg L(-1), 50 mg L(-1), 100 mg L(-1), 200 mg L(
      1), and 400 mg L(-1)) were tested in both cell types. Significant (P<0.05)
      decrease in cell proliferation were observed in cultured primary rat neurons
      starting with the dose of 100 mg L(-1) and in N2a neuroblastoma cells starting
      with 50 mg L(-1). TPO was not genotoxic in either cell type. In addition, TPO
      treatment at 10 mg L(-1), 25 mg L(-1), and 50 mg L(-1) increased TAC in primary
      rat neurons, but not in N2a cells. However, at concentrations above 50 mg L(-1)
      it increased TOS in both cell types. Our findings clearly demonstrate that TPO is
      a potent antiproliferative agent for brain tumour cells and may have potential as
      an anticancer agent, which needs to be further studied.

PMID- 24084351
TI  - Depth distribution of (137)Cs in anthrosol from the experimental field
      "Radmilovac" near Belgrade, Serbia.
AB  - This is a preliminary study of the depth distribution of (137)Cs radionuclides in
      cultivated anthrosol soil of a 15-year old peach tree plantation at the
      experimental field "Radmilovac" near Belgrade. Before planting, the soil was
      ploughed at the depth of 1 m. The soil had not been annually ploughed, irrigated
      and treated with mineral fertilizers for three years before sampling. Activity
      concentration for (137)Cs ranged from 1.8 Bq kg(-1) to 35 Bq kg(-1). Along the
      soil depth it varied highly, reaching as high a total variation coefficient as 83
      %. Radiocaesium distribution patterns depended on the extent of soil mixing in
      the plough layer, as it was mechanically transferred from the surface to the
      lower soil layers during cultivation. (137)Cs was associated with humus content
      and fixation to clay fractions in the soil. Our results single out soil's
      hygroscopic water as a valuable parameter for (137)Cs behaviour that could be
      used commonly if the measurement is standardised.

PMID- 24084352
TI  - Immunomodulation and oxidative stress in denim sandblasting workers: changes
      caused by silica exposure.
AB  - Workers in denim sandblasting are at a high risk of developing silicosis, an
      occupational lung disease caused by inhaling crystalline silica dust. The
      development and progress of silicosis is associated with the activation of the
      immune system and oxidative stress. In the former, interferon-gamma induces both
      neopterin release and the enzyme indoleamine [2, 3]-dioxygenase (IDO) in various
      cells. The determination of the kynurenine-to-tryptophan ratio and neopterin
      concentration has proven to be an efficient method to monitor the activation
      status of IDO and cellular immunity. The present study aimed to investigate
      whether occupational silica exposure leads to any alterations in neopterin
      levels, tryptophan degradation, and activities of superoxide dismutase (SOD) and
      catalase (CAT), agents in the antioxidant defense system. Fifty-five male denim
      sandblasting workers and twenty-two healthy men as controls were included. Mean
      neopterin and kynurenine levels, kynurenine-to-tryptophan ratio, and SOD activity
      were higher in subjects with silicosis compared to non-exposed controls (all,
      p<0.05). Neopterin levels and kynurenine-totryptophan ratios were positively
      correlated (p<0.05); however, no correlation was observed between length of
      employment and the measured parameters. Some of the measured parameters were
      significantly affected by the severity of the pathology. Our results suggest that
      silica exposure activates the cellular immune response. The increased neopterin
      levels and tryptophan degradation confirm the possibility of their use as an
      indicator of cellular immune response.

PMID- 24084353
TI  - Acute respiratory distress syndrome caused by methadone syrup.
AB  - Acute respiratory distress syndrome (ARDS) due to methadone (MTD) toxicity is a
      known but rather uncommon phenomenon. In most of the previously reported cases of
      MTD-related ARDS, MTD was ingested orally in the form of tablets in high or
      unknown amounts. Despite the findings from the available literature, this case
      report is aimed at demonstrating that even small amounts of MTD syrup can cause
      ARDS earlier than it is usually expected. We present a non-addicted MTD-overdosed
      patient who developed ARDS after ingesting a very small amount of MTD syrup. We
      suggest close monitoring of MTD-overdosed patients from at least 48 h to 72 h for
      possible respiratory complications such as pulmonary oedema.

PMID- 24084355
TI  - [History Of forensic medicine and the coroner system in the town of Bjelovar].
AB  - This review analyses historical sources on the development of forensic medicine
      and the coroner system in the town of Bjelovar over the past two centuries. The
      development of these two professional fields in the context of public health was
      regulated through a number of bylaws, such as Normativum Sanitatum from the time
      of the Habsburg Monarchy. Coroner examinations were performed by physicians,
      surgeons, and laymen using special instructions such as the famous booklet by
      nobleman and county medical officer Vilim Peicic from 1914. Forensic autopsy was
      performed by surgeons, primary or secondary hospital physicians in case of sudden
      or suspicious in-hospital deaths, whereas outpatient forensic autopsies were
      performed by county or town medical officers and district physicians at the
      request of investigating authorities (police, court, or general attorney's
      office). This historical review should serve as the basis for further historical
      research into this field in Croatia so as to obtain deeper insight into the
      development of forensic medicine and the coroner system, two professions that
      have always been a vital factor in public health.

PMID- 24084354
TI  - [Royal jelly: component efficiency, analysis, and standardisation].
AB  - Royal jelly is a viscous substance secreted by the hypopharyngeal and mandibular
      glands of worker honeybees (Apis mellifera) that contains a considerable amount
      of proteins, free amino acids, lipids, vitamins, sugars, and bioactive substances
      such as 10-hydroxy-trans-2-decenoic acid, antibacterial protein, and 350-kDa
      protein. These properties make it an attractive ingredient in various types of
      healthy foods. This article brings a brief review of the molecular mechanisms
      involved in the development of certain disorders that can be remedied by royal
      jelly, based on a selection of in vivo and in vitro studies. It also describes
      current understanding of the mechanisms and beneficial effects by which royal
      jelly helps to combat aging-related complications. Royal jelly has been reported
      to exhibit beneficial physiological and pharmacological effects in mammals,
      including vasodilative and hypotensive activities, antihypercholesterolemic
      activity, and antitumor activity. As its composition varies significantly (for
      both fresh and dehydrated samples), the article brings a few recommendations for
      defining new quality standards.

PMID- 24084356
TI  - A common misconception in the management of aluminium phosphide poisoning.

PMID- 24084357
TI  - Is the use of cardioactive steroids appropriate in managing aluminium phosphide
      poisoning-induced heart failure?

PMID- 24084358
TI  - Prolonged cultivation of hippocampal neural precursor cells shifts their
      differentiation potential and selects for aneuploid cells.
AB  - Neural precursor cells (NPCs) are lineage-restricted neural stem cells with
      limited self-renewal, giving rise to a broad range of neural cell types such as
      neurons, astrocytes, and oligodendrocytes. Despite this developmental potential,
      the differentiation capacity of NPCs has been controversially discussed
      concerning the trespassing lineage boundaries, for instance resulting in
      hematopoietic competence. Assessing their in vitro plasticity, we isolated
      nestin+/Sox2+, NPCs from the adult murine hippocampus. In vitro-expanded adult
      NPCs were able to form neurospheres, self-renew, and differentiate into neuronal,
      astrocytic, and oligodendrocytic cells. Although NPCs cultivated in early passage
      efficiently gave rise to neuronal cells in a directed differentiation assay,
      extensively cultivated NPCs revealed reduced potential for ectodermal
      differentiation. We further observed successful differentiation of long-term
      cultured NPCs into osteogenic and adipogenic cell types, suggesting that NPCs
      underwent a fate switch during culture. NPCs cultivated for more than 12 passages
      were aneuploid (abnormal chromosome numbers such as 70 chromosomes). Furthermore,
      they showed growth factor-independent proliferation, a hallmark of tumorigenic
      transformation. In conclusion, our findings substantiate the lineage restriction
      of NPCs from adult mammalian hippocampus. Prolonged cultivation results, however,
      in enhanced differentiation potential, which may be attributed to transformation
      events leading to aneuploid cells.

PMID- 24084359
TI  - Expression of macrophage markers in cryoglobulinemic glomerulonephritis - a
      possible role of CXCL9.
AB  - PURPOSE: Cryoglobulinemic glomerulonephritis (CGGN) is a type of
      membranoproliferative glomerulonephritis (MPGN) that develops in patients with
      systemic cryoglobulinemia. To date the exact pathogenesis of CGGN remains
      unclear. It has been suggested that macrophages may be significant contributors
      to the glomerular injury in this disease. In our study we attempt to characterize
      the macrophages in human CGGN using classical activation and regulatory
      macrophage markers. MATERIAL AND METHOD: We searched our database for renal
      biopsy cases of CGGN. Macrophages were detected using a monoclonal anti-CD68
      antibody. Two groups of macrophage markers were used: classical activation
      markers, including iNOS, CXCL9 and CCL20, and regulatory markers: SPHK1 and
      LIGHT. The stains were performed using immunohistochemical method. RESULTS: Five
      patients with CGGN were identified. Four patients had systemic cryoglobulinemia
      and two had a serological evidence of hepatitis C virus infection. In all cases
      the glomeruli contained numerous macrophages. Staining for activatory macrophage
      markers revealed a strong nuclear staining for CXCL9 in numerous cells, including
      those corresponding to the macrophage location. Staining for the other activatory
      markers, as well as staining for regulatory markers, was not significant.
      CONCLUSION: In this study of human CGGN we showed a striking expression of
      cytokine CXCL9, a classical macrophage activation marker, by the macrophages and
      possibly other cell types within the glomeruli. This observation points to the
      possible role of classically activated macrophages in the pathogenesis of MPGN.
      If this observation is confirmed on a larger group of patients, the cytokine
      CXCL9 could become a potential therapeutic target for human CGGN.

PMID- 24084360
TI  - Effects on vocal range and voice quality of singing voice training: the
      classically trained female voice.
AB  - OBJECTIVES: A longitudinal study was performed on the acoustical effects of
      singing voice training under a given study program, using the voice range profile
      (VRP). STUDY DESIGN: Pretraining and posttraining recordings were made of
      students who participated in a 3-year bachelor singing study program. A
      questionnaire that included questions on optimal range, register use,
      classification, vocal health and hygiene, mixing technique, and training goals
      was used to rate and categorize self-assessed voice changes. Based on the
      responses, a subgroup of 10 classically trained female voices was selected, which
      was homogeneous enough for effects of training to be identified. METHODS: The VRP
      perimeter contour was analyzed for effects of voice training. Also, a mapping
      within the VRP of voice quality, as expressed by the crest factor, was used to
      indicate the register boundaries and to monitor the acoustical consequences of
      the newly learned vocal technique of "mixed voice." VRPs were averaged across
      subjects. Findings were compared with the self-assessed vocal changes. RESULTS:
      Pre/post comparison of the average VRPs showed, in the midrange, (1) a decrease
      in the VRP area that was associated with the loud chest voice, (2) a reduction of
      the crest factor values, and (3) a reduction of maximum sound pressure level
      values. The students' self-evaluations of the voice changes appeared in some
      cases to contradict the VRP findings. CONCLUSIONS: VRPs of individual voices were
      seen to change over the course of a singing education. These changes were
      manifest also in the average group. High-resolution computerized recording,
      complemented with an acoustic register marker, allows a meaningful assessment of
      some effects of training, on an individual basis and for groups that comprise
      singers of a specific genre. It is argued that this kind of investigation is
      possible only within a focused training program, given by a faculty who has
      agreed on the goals.

PMID- 24084361
TI  - Quality measurement and benchmarking of HPV vaccination services: a new approach.
AB  - BACKGROUND: A new measurement process based upon a well-defined mathematical
      model was applied to evaluate the quality of human papillomavirus (HPV)
      vaccination centers in 3 of 12 Local Health Units (ASLs) within the Lazio Region
      of Italy. The quality aspects considered for evaluation were communicational
      efficiency, organizational efficiency and comfort. RESULTS: The overall maximum
      achievable value was 86.10%, while the HPV vaccination quality scores for ASL1,
      ASL2 and ASL3 were 73.07%, 71.08%, and 67.21%, respectively. CONCLUSIONS: With
      this new approach it is possible to represent the probabilistic reasoning of a
      stakeholder who evaluates the quality of a healthcare provider. All ASLs had
      margins for improvements and optimal quality results can be assessed in terms of
      better performance conditions, confirming the relationship between the resulting
      quality scores and HPV vaccination coverage. METHODS: The measurement process was
      structured into three steps and involved four stakeholder categories: doctors,
      nurses, parents and vaccinated women. In Step 1, questionnaires were administered
      to collect different stakeholders' points of view (i.e., subjective data) that
      were elaborated to obtain the best and worst performance conditions when
      delivering a healthcare service. Step 2 of the process involved the gathering of
      performance data during the service delivery (i.e., objective data collection).
      Step 3 of the process involved the elaboration of all data: subjective data from
      step 1 are used to define a "standard" to test objective data from step 2. This
      entire process led to the creation of a set of scorecards. Benchmarking is
      presented as a result of the probabilistic meaning of the evaluated scores.

PMID- 24084362
TI  - Pre-clinical evaluation of tyrosine kinase inhibitors for treatment of acute
      leukemia.
AB  - Receptor tyrosine kinases have been implicated in the development and progression
      of many cancers, including both leukemia and solid tumors, and are attractive
      druggable therapeutic targets. Here we describe an efficient four-step strategy
      for pre-clinical evaluation of tyrosine kinase inhibitors (TKIs) in the treatment
      of acute leukemia. Initially, western blot analysis is used to confirm target
      inhibition in cultured leukemia cells. Functional activity is then evaluated
      using clonogenic assays in methylcellulose or soft agar cultures. Experimental
      compounds that demonstrate activity in cell culture assays are evaluated in vivo
      using NOD-SCID-gamma (NSG) mice transplanted orthotopically with human leukemia
      cell lines. Initial in vivo pharmacodynamic studies evaluate target inhibition in
      leukemic blasts isolated from the bone marrow. This approach is used to determine
      the dose and schedule of administration required for effective target inhibition.
      Subsequent studies evaluate the efficacy of the TKIs in vivo using luciferase
      expressing leukemia cells, thereby allowing for non-invasive bioluminescent
      monitoring of leukemia burden and assessment of therapeutic response using an in
      vivo bioluminescence imaging system. This strategy has been effective for
      evaluation of TKIs in vitro and in vivo and can be applied for identification of
      molecularly-targeted agents with therapeutic potential or for direct comparison
      and prioritization of multiple compounds. 

PMID- 24084363
TI  - The fear of 5-ALA--is it warranted?

PMID- 24084364
TI  - Mercy health promoter: a paradigm for just health care.
AB  - The foreign-born population in the United States, according to the "Current
      Populations Report" published in 2010, is estimated to exceed 39.9 million, or
      "12.9 percent of the U.S. population." The increase in foreign-born peoples and
      their need for health care is a complicated issue facing many cities, health
      systems and hospitals. Over the course of the past few years Mercy Hospital of
      Philadelphia has treated increasing numbers of foreign-born African patients. The
      majority have been presenting in the late stages of disease. The increase of
      foreign-born documented and undocumented African patients seen by Mercy Hospitals
      seems to reflect a foreign-born population "boom" in Philadelphia over the past
      decade. To meet the needs of this growing population, the Mercy Hospital Task
      Force on African Immigration and the Institute of Catholic Bioethics at Saint
      Joseph's University designed a program that centers on the third world concept of
      "Health Promoters." This program is intended to serve as one possible solution
      for hospitals to cost-effectively manage the care of this growing percentage of
      foreign-born individuals in the population. This notion of a "Health Promoter"
      program in Philadelphia is unique as one of those rare occasions when a third
      world concept is being utilized in a first world environment. It is also unique
      in that it can serve as a paradigm for other hospitals in the United States to
      meet the growing need of health care for the undocumented population. As of
      November 2012 the Mercy Hospital of Philadelphia clinic became operative for
      patients who were referred from the Health Promoter clinics. To date, a total of
      forty-two patients have actively participated in the screenings, sixteen of which
      have been referred to Mercy Hospital of Philadelphia clinic for further
      evaluation. More than 75% of patient referrals were a result of high blood
      pressure. According to the American Medical Association, readings of 140-159 mmHg
      and above are indicative of stage 1 hypertension. Among those who presented at
      the Health Promoter screenings the mean systolic pressure for males was 140 mmHg
      and for females was 140.48 mmHg. 

PMID- 24084365
TI  - Evidence for the role of wheat eukaryotic translation initiation factor 3 subunit
      g (TaeIF3g) in abiotic stress tolerance.
AB  - The gene encoding eIF3g (TaeIF3g), one of the 11 subunits of eukaryotic
      translation initiation factor 3 (eIF3), was cloned from wheat for carrying out
      its functional analysis. Transgenic expression of TaeIF3g enhanced the tolerance
      of TaeIF3g-overexpressing parental yeast cells and Arabidopsis plants under
      different abiotic stress conditions. Compared to untransformed plants, TaeIF3g
      overexpressing Arabidopsis thaliana plants exhibited significantly higher
      survival rate, soluble proteins and photosynthetic efficiency, and enhanced
      protection against photooxidative stress under drought conditions. This study
      provides first evidence that TaeIF3g imparts stress tolerance and could be a
      potential candidate gene for developing crop plants tolerant to abiotic stress.

PMID- 24084366
TI  - Evolution of the tRNA gene family in mitochondrial genomes of five Meretrix clams
      (Bivalvia, Veneridae).
AB  - In contrast to the extreme conservation of nuclear-encoded tRNAs, organization of
      the mitochondrial (mt) tRNA gene family in invertebrates is highly dynamic and
      rapidly evolving. While gene duplication and loss, gene isomerism, recruitment,
      and rearrangements have occurred sporadically in several invertebrate lineages,
      little is known regarding the pattern of their evolution. Comparisons of
      invertebrate mt genomes at a generic level can be extremely helpful in
      investigating evolutionary patterns of variation, as intermediate stages of the
      process may be identified. Variation of mitochondrial tRNA organization among
      Meretrix clams provides good materials to investigate mt tRNA evolution. We
      characterized the complete mt genome of the lyrate Asiatic hard clam Meretrix
      lyrata, re-annotated tRNAs of four previously sequenced Meretrix clams, and
      undertook an intensive comparison of tRNA gene families in these clams. Our
      results 1) provide evidence that the commonly observed duplication of trnM may
      have occurred independently in different bivalve lineages and, based on the
      higher degree of trnM gene similarity, may have occurred more recently than
      expected; 2) suggest that "horizontal" evolution may have played an important
      role in tRNA gene family evolution based on frequent gene duplications and gene
      recruitment events; and 3) reveal the first case of isoacceptor "vertical" tRNA
      gene recruitment (VTGR) and present the first clear evidence that VTGR allows
      rapid evolution of tRNAs. We identify the trnS(-UCR) gene in Meretrix clams,
      previously considered missing in this lineage, and speculate that trnS(-UCR)
      lacking the D-arm in both M. lyrata and Meretrix lamarckii may represent the
      ancestral status. Phylogenetic analysis based on 13 concatenate protein-coding
      genes provided opportunities to detect rapidly evolved tRNA genes via VTGR and
      gene isomerism processes. This study suggests that evolution of the mt tRNA gene
      family in bivalves is more complex than previously thought and that comparison of
      several congeneric species is a useful strategy in investigating evolutionary
      patterns and dynamics of mt tRNA genes.

PMID- 24084367
TI  - MicroRNA-148a: a potential therapeutic target for cancer.
AB  - MicroRNA-148a (miR-148a) which suppresses tumor growth by directly decreasing
      DNMT1 expression has been demonstrated as an important role for cancer therapy.
      The mechanisms for miR-148a in cancer will become potential future researches. 

PMID- 24084368
TI  - Cytogenetic response based on revised IPSS cytogenetic risk stratification and
      minimal residual disease monitoring by FISH in MDS patients treated with low-dose
      decitabine.
AB  - The features of cytogenetic response have been not well described in
      myelodysplastic syndrome (MDS) patients receiving low-dose decitabine treatment.
      In this study, we observed and analyzed the response characteristics based on the
      revised IPSS (IPSS-R) cytogenetic risk stratification in eighty-seven MDS
      patients who received low-dose decitabine treatment (15-20 mg/M(2)/d*5/per
      course). Twenty-seven of 44 patients (61.3%) with abnormal karyotypes achieved a
      cytogenetic response, including 18 cases with complete cytogenetic response
      (cCR). The patients carrying poor or very poor karyotypes achieved better
      clinical and cytogenetic response than those with intermediate or good
      karyotypes. Among the patients with poor or very poor karyotypes, those carrying
      chromosome 7 aberrance showed a better treatment response than the other
      patients. Four patients (22.2%) of the patients who achieved clinical CR
      presented with a cytogenetic PR (partial response) or NR (no response). Over 5%
      of the clonal cells determined by FISH analysis were in the two patients who
      presented cytogenetic CR. Longer median OS (24 months) were observed in the
      patients who achieved a cytogenetic response than in those who did not (12
      months) (P=0.007). The patients with poor or very poor karyotypes could achieve
      survival comparable to that of the patients with good or very good karyotypes
      after decitabine treatment (18 vs. 20 months, P=0.365). IPSS-R cytogenetic risk
      stratification could be used to predict the clinical and cytogenetic response to
      decitabine treatment in MDS patients, and the predicting effect may be related to
      chromosome 7 involvement. Analysis with FISH and G-banding should be available in
      determining the minimal residual disease in MDS patients after treatment.

PMID- 24084370
TI  - Dedicated bibliometrics: a more appropriate impact factor for specialty journals?

PMID- 24084371
TI  - Screening for celiac disease.

PMID- 24084369
TI  - Lipidomic profiling of bioactive lipids by mass spectrometry during microbial
      infections.
AB  - Bioactive lipid mediators play crucial roles in promoting the induction and
      resolution of inflammation. Eicosanoids and other related unsaturated fatty acids
      have long been known to induce inflammation. These signaling molecules can
      modulate the circulatory system and stimulate immune cell infiltration into the
      site of infection. Recently, DHA- and EPA-derived metabolites have been
      discovered to promote the resolution of inflammation, an active process. Not only
      do these molecules stop the further infiltration of immune cells, they prompt non
      phlogistic phagocytosis of apoptotic neutrophils, stimulating the tissue to
      return to homeostasis. After the rapid release of lipid precursors from the
      plasma membrane upon stimulation, families of enzymes in a complex network
      metabolize them to produce a large array of lipid metabolites. With current
      advances in mass spectrometry, the entire lipidome can be accurately quantified
      to assess the immune response upon microbial infection. In this review, we
      discuss the various lipid metabolism pathways in the context of the immune
      response to microbial pathogens, as well as their complex network interactions.
      With the advancement of mass spectrometry, these approaches have also been used
      to characterize the lipid mediator response of macrophages and neutrophils upon
      immune stimulation in vitro. Lastly, we describe the recent efforts to apply
      systems biology approaches to dissect the role of lipid mediators during
      bacterial and viral infections in vivo. 

PMID- 24084373
TI  - Donor human milk for preterm infants: current evidence and research directions.
AB  - The Committee on Nutrition of the European Society for Pediatric
      Gastroenterology, Hepatology, and Nutrition aims to document the existing
      evidence of the benefits and common concerns deriving from the use of donor human
      milk (DHM) in preterm infants. The comment also outlines gaps in knowledge and
      gives recommendations for practice and suggestions for future research
      directions. Protection against necrotizing enterocolitis is the major clinical
      benefit deriving from the use of DHM when compared with formula. Limited data
      also suggest unfortified DHM to be associated with improved feeding tolerance and
      with reduced cardiovascular risk factors during adolescence. Presence of a human
      milk bank (HMB) does not decrease breast-feeding rates at discharge, but
      decreases the use of formula during the first weeks of life. This commentary
      emphasizes that fresh own mother's milk (OMM) is the first choice in preterm
      infant feeding and strong efforts should be made to promote lactation. When OMM
      is not available, DHM is the recommended alternative. When neither OMM nor DHM is
      available, preterm formula should be used. DHM should be provided from an
      established HMB, which follows specific safety guidelines. Storage and processing
      of human milk reduces some biological components, which may diminish its health
      benefits. From a nutritional point of view, DHM, like HM, does not meet the
      requirements of preterm infants, necessitating a specific fortification regimen
      to optimize growth. Future research should focus on the improvement of milk
      processing in HMB, particularly of heat treatment; on the optimization of HM
      fortification; and on further evaluation of the potential clinical benefits of
      processed and fortified DHM. 

PMID- 24084372
TI  - Assessment and management of nutrition and growth in Rett syndrome.
AB  - OBJECTIVES: We developed recommendations for the clinical management of poor
      growth and weight gain in Rett syndrome through evidence review and the consensus
      of an expert panel of clinicians. METHODS: Initial draft recommendations were
      created based upon literature review and 34 open-ended questions in which the
      literature was lacking. Statements and questions were made available to an
      international, multidisciplinary panel of clinicians in an online format and a
      Microsoft Word-formatted version of the draft via e-mail. Input was sought using
      a 2-stage modified Delphi process to reach consensus. Items included clinical
      assessment of growth, anthropometry, feeding difficulties and management to
      increase energy intake, decrease feeding difficulties, and consideration of
      gastrostomy. RESULTS: Agreement was achieved on 101 of 112 statements. A
      comprehensive approach to the management of poor growth in Rett syndrome is
      recommended that takes into account factors such as feeding difficulties and
      nutritional needs. A body mass index of approximately the 25th centile can be
      considered as a reasonable target in clinical practice. Gastrostomy is indicated
      for extremely poor growth, if there is risk of aspiration and if feeding times
      are prolonged. CONCLUSIONS: These evidence- and consensus-based recommendations
      have the potential to improve care of nutrition and growth in a rare condition
      and stimulate research to improve the present limited evidence base.

PMID- 24084374
TI  - Chromogranin-A staining reveals enteric anendocrinosis in unexplained congenital
      diarrhea.

PMID- 24084375
TI  - Heavy metal pollution in coastal areas of South China: a review.
AB  - Coastal areas of South China face great challenges due to heavy metal
      contamination caused by rapid urbanization and industrialization. In this paper,
      more than 90 articles on levels, distributions, and sources of heavy metals in
      sediments and organisms were collected to review the status of heavy metal
      pollution along coastal regions of South China. The results show that heavy metal
      levels were closely associated with local economic development. Hong Kong and the
      Pearl River Estuary were severely contaminated by heavy metals. However,
      concentrations of heavy metals in sediments from Hong Kong have continually
      decreased since the early 1990 s. High levels of heavy metals were found in biota
      from Lingdingyang in Guangdong province. Mollusks had higher concentrations of
      heavy metals than other species. Human health risk assessments suggested that
      levels of heavy metals in some seafood from coastal areas of South China exceeded
      the safety limit.

PMID- 24084376
TI  - Acid-volatile sulfide and simultaneously extracted metals in surface sediments of
      the southwestern coastal Laizhou Bay, Bohai Sea: concentrations, spatial
      distributions and the indication of heavy metal pollution status.
AB  - Surface sediments were collected from the coastal waters of southwestern Laizhou
      Bay and the rivers it connects with during summer and autumn 2012. The acid
      volatile sulfide (AVS) and simultaneously extracted metals (SEM) were measured to
      assess the sediment quality. The results showed that not all sediments with [SEM]
      [AVS]>0 were capable of causing toxicity because the organic carbon is also an
      important metal-binding phase in sediments. Suppose the sediments had not been
      disturbed and the criteria of US Environmental Protection Agency had been
      followed, heavy metals in this area had no adverse biological effects in both
      seasons except for few riverine samples. The major ingredient of SEM was Zn,
      whereas the contribution of Cd - the most toxic metal studied - to SEM was <1%.
      The distributions of AVS and SEM in riverine sediments were more easily affected
      by anthropogenic activity compared with those in marine sediments. 

PMID- 24084377
TI  - Clinical characteristics and economic consequence of Klebsiella pneumoniae liver
      abscess in Taiwan.
AB  - BACKGROUND: Klebsiella pneumoniae liver abscess (KPLA) has emerged as an endemic
      disease in Taiwan, and its prevalence has been increasing in east Asian countries
      in the past three decades. The utilization of healthcare resources associated
      with KPLA is assumed to be substantial, and may be of future concern. This study
      investigated the clinical characteristics and economic burden of KPLA in Taiwan
      in 2011 and 2012. METHODS: Adult patients with KPLA were identified
      retrospectively in a tertiary medical center in Taiwan from January 2011 to
      December 2012. The clinical characteristics, total and daily hospitalization
      expenditure, and the risk factors for the costs of KPLA were analyzed. RESULTS:
      Among patients with KPLA, the median cost was $5290.80 in US dollars, and the
      mean cost was $6337.50 +/- $4363.40. Length of hospital stay was the only
      independent risk factor for the high total hospitalization expenditure. The
      duration of antibiotic use was nearly the same as the length of hospital stay.
      The prolonged stay in the general ward (>=21 days) also contributed to the high
      total cost of hospitalization. The independent risk factors for the high average
      daily cost of hospitalization were a higher Charlson Comorbidity Index and the
      requirement of intensive care on admission. CONCLUSION: The current study is the
      first to demonstrate the high economic burden resulting from KPLA in a medical
      center in Taiwan. Standardizing the treatment protocol for KPLA inpatients and
      introducing an outpatient parenteral antimicrobial therapy center to reduce the
      length of stay may reduce costs, whereas development of a vaccine may be
      necessary to tackle endemic KPLA in the future.

PMID- 24084378
TI  - Production and characterisation of a monoclonal antibody that recognises the
      chicken CSF1 receptor and confirms that expression is restricted to macrophage
      lineage cells.
AB  - Macrophages contribute to innate and acquired immunity as well as many aspects of
      homeostasis and development. Studies of macrophage biology and function in birds
      have been hampered by a lack of definitive cell surface markers. As in mammals,
      avian macrophages proliferate and differentiate in response to CSF1 and IL34,
      acting through the shared receptor, CSF1R. CSF1R mRNA expression in the chicken
      is restricted to macrophages and their progenitors. To expedite studies of avian
      macrophage biology, we produced an avian CSF1R-Fc chimeric protein and generated
      a monoclonal antibody (designated ROS-AV170) against the chicken CSF1R using the
      chimeric protein as immunogen. Specific binding of ROS-AV170 to CSF1R was
      confirmed by FACS, ELISA and immunohistochemistry on tissue sections. CSF1 down
      regulated cell surface expression of the CSF1R detected with ROS-AV170, but the
      antibody did not block CSF1 signalling. Expression of CSF1R was detected on the
      surface of bone marrow progenitors only after culture in the absence of CSF1, and
      was induced during macrophage differentiation. Constitutive surface expression of
      CSF1R distinguished monocytes from other myeloid cells, including heterophils and
      thrombocytes. This antibody will therefore be of considerable utility for the
      study of chicken macrophage biology.

PMID- 24084379
TI  - Lanthanide chelate complementation and hydrolysis enhanced luminescent chelate in
      real-time reverse transcription polymerase chain reaction assays for KLK3
      transcripts.
AB  - The requirement for high-performance reporter probes in real-time detection of
      polymerase chain reaction (PCR) has led to the use of time-resolved fluorometry
      of lanthanide chelates. The aim of this study was to investigate the
      applicability of the principle of lanthanide chelate complementation (LCC) in
      comparison with a method based on hydrolysis enhancement and quenching of intact
      probes. A real-time reverse transcription (RT) PCR assay for kallikrein-related
      peptidase 3 (KLK3, model analyte) was developed by using the LCC detection
      method. Both detection methods were tested with a standard series of purified PCR
      products, 20 prostatic tissues, 20 healthy and prostate cancer patient blood
      samples, and female blood samples spiked with LNCaP cells. The same limit of
      detection was obtained with both methods, and two cycles earlier detection with
      the LCC method was observed. KLK3 messenger RNA (mRNA) was detected in all tissue
      samples and in 1 of 20 blood samples identically with both methods. The
      background was 30 times lower, and the signal-to-background (S/B) ratio was 3
      times higher, when compared with the reference method. Use of the new reporter
      method provided similar sensitivity and specificity as the reference method. The
      lower background, the improved S/B ratio, and the possibility of melting curve
      analysis and single nucleotide polymorphism (SNP) detection could be advantages
      for this new reporter probe. 

PMID- 24084380
TI  - Multi-fragment site-directed mutagenic overlap extension polymerase chain
      reaction as a competitive alternative to the enzymatic assembly method.
AB  - Methods for introducing multiple site-directed mutations are important
      experimental tools in molecular biology. Research areas that use these methods
      include the investigation of various protein modifications in cellular processes,
      modifying proteins for efficient recombinant expression, and the stabilization of
      mRNAs to allow for increased protein expression. Introducing multiple site
      directed mutations is also an important tool in the field of synthetic biology.
      There are two main methods used in the assembling of fragments generated by
      mutagenic primers: enzymatic assembly and overlap extension polymerase chain
      reaction (OE-PCR). In this article, we present an improved OE-PCR method that can
      be used for the generation of large DNA fragments (up to 7.4 kb) where at least
      13 changes can be introduced using a genomic template. The improved method is
      faster (due to fewer reaction steps) and more accurate (due to fewer PCR cycles),
      meaning that it can effectively compete with the enzymatic assembly method. Data
      presented here show that the site-directed mutations can be introduced anywhere
      between 50 and 1800 bp from each other. The method is highly reliable and
      predicted to be applicable to most DNA engineering when the introduction of
      multiple changes in a DNA sequence is required.

PMID- 24084381
TI  - Sleep benefit in Parkinson's disease is associated with short sleep times.
AB  - Sleep benefit in Parkinson's disease is characterized by restoration of mobility
      upon awakening from sleep and prior to drug intake. With this study, we aimed at
      assessing clinical and nocturnal sleep correlates of this phenomenon. We recorded
      motor and non-motor symptoms in 131 Parkinson patients with and without sleep
      benefit, as assessed by questionnaires. Polysomnography recordings were performed
      in 60 of these patients. Thirty-nine Parkinson patients (30%) reported sleep
      benefit. Motor symptoms, measures of sleepiness, fatigue, depression, anxiety,
      sleep-wake disorders, and dopaminergic treatment were not associated with sleep
      benefit, and most polysomnography measures were similar between both groups.
      However, Parkinson patients with sleep benefit had shorter total sleep times and
      longer sleep latencies at nocturnal polysomnography. The link between the
      occurrence of sleep benefit and shorter nocturnal sleep in Parkinson's disease
      remains unclear. 

PMID- 24084382
TI  - Validation and attempts of revision of the MDS-recommended tests for the
      screening of Parkinson's disease dementia.
AB  - The Movement Disorders Society (MDS) formulated diagnostic criteria and
      assessment guidelines for the screening of dementia in Parkinson's disease (PD).
      We carried out a validation of the cognitive measures suggested in the screening
      algorithm (i.e. the Mini Mental State Examination - MMSE - total score, serial 7s
      subtraction, 3-word recall, pentagons copy, and one minute letter fluency) in 86
      patients with PD. Thirty-six percent of participants were diagnosed with dementia
      using the MDS algorithm, but with the Dementia Rating Scale instead of the MMSE.
      The original MDS procedure misclassified 11 patients (12.8%) as false negatives
      and 3 (3.5%) as false positives, leading to 65% sensitivity and 95% specificity.
      The main reason for misdiagnoses was insensitivity of the MMSE total score. Three
      attempts were made to reach a better screening performance, which warrants high
      sensitivity more than high specificity: 1. exclusion of the MMSE total score as a
      diagnostic requirement; 2. determination of a better cut off through Receiver
      Operating Characteristic curve analysis; 3. replacement of the MMSE with the
      equally undemanding, but more PD-specific, Mini Mental Parkinson. The first two
      strategies generally yielded high sensitivity, but poor specificity. The best
      outcome was achieved using a Mini Mental Parkinson total score <27 as cognitive
      criterion: sensitivity was 87% and negative predictive value was 90%; however,
      specificity was only 67%. Our findings seem to suggest that MDS practical
      guidelines are specific, but might benefit from the use of more PD-oriented tools
      than the MMSE in terms of sensitivity.

PMID- 24084383
TI  - Myocardin-related transcription factor A is up-regulated by 17beta-estradiol and
      promotes migration of MCF-7 breast cancer cells via transactivation of MYL9 and
      CYR61.
AB  - Many lines of evidence have suggested that estrogen plays important roles not
      only in the initiation and proliferation of breast cancer, but also in cancer
      metastasis. However, the mechanistic basis of the latter events is poorly
      understood. In addition, recent studies have suggested that myocardin-related
      transcription factor A (MRTF-A) might be related to cancer metastasis. However,
      as reports are contradictory, certain of its roles still remain confusing. In the
      present study, we showed that excessive 17beta-estradiol could promote the
      migration of MCF-7 breast cancer cells and up-regulate the expression of MRTF-A,
      myosin regulatory light chain 9 (MYL9), and cysteine-rich angiogenic inducer 61
      (CYR61). Overexpression of MRTF-A significantly promoted the migration of MCF-7
      cells through its transactivation effects on MYL9 and CYR61 genes, while RNA
      interference-mediated knockdown of MRTF-A strongly inhibited transcription and
      expression of the target genes and reduced the migration ability of MCF-7 cells.
      These results provided novel evidence supporting the metastasis-promoting
      functions of MRTF-A, and implied that MRTF-A might be a switch for the estrogen
      pathway to change its proliferation-promoting roles into migration-stimulating
      roles in breast cancer. 

PMID- 24084384
TI  - Are patterns of bone loss in anorexic and postmenopausal women similar?
      Preliminary results using high resolution peripheral computed tomography.
AB  - This study intended to compare bone density and architecture in three groups of
      women: young women with anorexia nervosa (AN), an age-matched control group of
      young women, and healthy late postmenopausal women. Three-dimensional peripheral
      quantitative high resolution computed-tomography (HR-pQCT) at the ultradistal
      radius, a technology providing measures of cortical and trabecular bone density
      and microarchitecture, was performed in the three cohorts. Thirty-six women with
      AN aged 18-30 years (mean duration of AN: 5.8 years), 83 healthy late
      postmenopausal women aged 70-81 as well as 30 age-matched healthy young women
      were assessed. The overall cortical and trabecular bone density (D100), the
      absolute thickness of the cortical bone (CTh), and the absolute number of
      trabecules per area (TbN) were significantly lower in AN patients compared with
      healthy young women. The absolute number of trabecules per area (TbN) in AN and
      postmenopausal women was similar, but significantly lower than in healthy young
      women. The comparison between AN patients and post-menopausal women is of
      interest because the latter reach bone peak mass around the middle of the fertile
      age span whereas the former usually lose bone before reaching optimal bone
      density and structure. This study shows that bone mineral density and bone
      compacta thickness in AN are lower than those in controls but still higher than
      those in postmenopause. Bone compacta density in AN is similar as in controls.
      However, bone inner structure in AN is degraded to a similar extent as in
      postmenopause. This last finding is particularly troubling.

PMID- 24084385
TI  - TRPV4 deficiency causes sexual dimorphism in bone metabolism and osteoporotic
      fracture risk.
AB  - We explored the role of transient receptor potential vanilloid 4 (TRPV4) in
      murine bone metabolism and association of TRPV4 gene variants with fractures in
      humans. Urinary and histomorphometrical analyses demonstrated reduced osteoclast
      activity and numbers in male Trpv4(-/-) mice, which was confirmed in bone marrow
      derived osteoclast cultures. Osteoblasts and bone formation as shown by serum
      procollagen type 1 amino-terminal propeptide and histomorphometry, including
      osteoid surface, osteoblast and osteocyte numbers were not affected in vivo.
      Nevertheless, osteoblast differentiation was enhanced in Trpv4(-/-) bone marrow
      cultures. Cortical and trabecular bone mass was 20% increased in male Trpv4(-/-)
      mice, compared to sex-matched wild type (Trpv4(+/+)) mice. However, at the same
      time intracortical porosity was increased and bone matrix mineralization was
      reduced. Together, these lead to a maximum load, stiffness and work to failure of
      the femoral bone, which were not different compared to Trpv4(+/+) mice, while the
      bone material was less resistant to stress and less elastic. The differential
      impacts on these determinants of bone strength were likely responsible for the
      lack of any changes in whole bone strength in the Trpv4(-/-) mice. None of these
      skeletal parameters were affected in female Trpv4(-/-) mice. The T-allele of
      rs1861809 SNP in the TRPV4 locus was associated with a 30% increased risk (95%
      CI: 1.1-1.6; p=0.013) for non-vertebral fracture risk in men, but not in women,
      in the Rotterdam Study. Meta-analyses with the population-based LASA study
      confirmed the association with non-vertebral fractures in men. This was lost when
      the non-population-based studies Mr. OS and UFO were included. In conclusion,
      TRPV4 is a male-specific regulator of bone metabolism, a determinant of bone
      strength, and a potential risk predictor for fractures through regulation of bone
      matrix mineralization and intra-cortical porosity. This identifies TRPV4 as a
      unique sexually dimorphic therapeutic and/or diagnostic candidate for
      osteoporosis. 

PMID- 24084386
TI  - Rethinking vaccine policy making in an era of vaccine hesitancy: time to rebuild,
      not remodel?
AB  - Recently in this journal, David Ropeik argued for imposing additional burdens
      upon individuals who refused vaccines for themselves or for their children.
      Specifically, Ropeik advocated for policies that would decrease the ease of
      claiming vaccine exemptions and restricting unvaccinated children participation
      in social activities. We argue that, in order to derive the optimal societal
      benefit from modern vaccinology in an era of vaccine hesitancy, we need to
      consider doing more than conventional remodeling of current policies. We may need
      to fundamentally redesign and rebuild. 

PMID- 24084388
TI  - Protocols for implementing an Escherichia coli based TX-TL cell-free expression
      system for synthetic biology.
AB  - Ideal cell-free expression systems can theoretically emulate an in vivo cellular
      environment in a controlled in vitro platform. This is useful for expressing
      proteins and genetic circuits in a controlled manner as well as for providing a
      prototyping environment for synthetic biology. To achieve the latter goal, cell
      free expression systems that preserve endogenous Escherichia coli transcription
      translation mechanisms are able to more accurately reflect in vivo cellular
      dynamics than those based on T7 RNA polymerase transcription. We describe the
      preparation and execution of an efficient endogenous E. coli based transcription
      translation (TX-TL) cell-free expression system that can produce equivalent
      amounts of protein as T7-based systems at a 98% cost reduction to similar
      commercial systems. The preparation of buffers and crude cell extract are
      described, as well as the execution of a three tube TX-TL reaction. The entire
      protocol takes five days to prepare and yields enough material for up to 3000
      single reactions in one preparation. Once prepared, each reaction takes under 8
      hr from setup to data collection and analysis. Mechanisms of regulation and
      transcription exogenous to E. coli, such as lac/tet repressors and T7 RNA
      polymerase, can be supplemented. Endogenous properties, such as mRNA and DNA
      degradation rates, can also be adjusted. The TX-TL cell-free expression system
      has been demonstrated for large-scale circuit assembly, exploring biological
      phenomena, and expression of proteins under both T7- and endogenous promoters.
      Accompanying mathematical models are available. The resulting system has unique
      applications in synthetic biology as a prototyping environment, or "TX-TL
      biomolecular breadboard."

PMID- 24084389
TI  - Infectious diseases: a friend in need.

PMID- 24084387
TI  - Mechanosensitivity in the upper extremity following breast cancer treatment.
AB  - STUDY DESIGN: Descriptive, cross-sectional. INTRODUCTION: Breast cancer (BC)
      treatments place the nervous system at risk, which may contribute to upper
      extremity (UE) mechanosensitivity. PURPOSE OF THE STUDY: To evaluate elbow
      extension range of motion (EE-ROM) during upper limb neurodynamic testing (ULNT)
      post-BC treatment. METHODS: ULNT EE-ROM was measured for 145 women post-BC
      treatment. Women were sub-grouped by presence/absence of pain and lymphedema.
      RESULTS: Mean EE-ROM during ULNT1 was -22.3 degrees  (SD 11.9 degrees ) on the
      unaffected limb and -25.99 degrees  (SD 13.1 degrees ) on the affected limb. The
      women with pain and lymphedema had the greatest limitation in EE-ROM during ULNT1
      testing, particularly of their affected limb (-33.8 degrees , SD 12.9). Symptoms
      were reported more frequently in the affected chest, shoulder, arm, elbow, and
      hand. The intensity of symptoms was greater at the affected chest (p = 0.046),
      shoulder (p = 0.033) and arm (p = 0.039). CONCLUSIONS: Women with lymphedema and
      pain after BC treatment may present with altered neural mechanosensitivity. LEVEL
      OF EVIDENCE: 3a.

PMID- 24084390
TI  - Automatic mapping of visual cortex receptive fields: a fast and precise
      algorithm.
AB  - An important issue for neurophysiological studies of the visual system is the
      definition of the region of the visual field that can modify a neuron's activity
      (i.e., the neuron's receptive field - RF). Usually a trade-off exists between
      precision and the time required to map a RF. Manual methods (qualitative) are
      fast but impose a variable degree of imprecision, while quantitative methods are
      more precise but usually require more time. We describe a rapid quantitative
      method for mapping visual RFs that is derived from computerized tomography and
      named back-projection. This method finds the intersection of responsive regions
      of the visual field based on spike density functions that are generated over time
      in response to long bars moving in different directions. An algorithm corrects
      the response profiles for latencies and allows for the conversion of the time
      domain into a 2D-space domain. The final product is an RF map that shows the
      distribution of the neuronal activity in visual-spatial coordinates. In addition
      to mapping the RF, this method also provides functional properties, such as
      latency, orientation and direction preference indexes. This method exhibits the
      following beneficial properties: (a) speed; (b) ease of implementation; (c)
      precise RF localization; (d) sensitivity (this method can map RFs based on few
      responses); (e) reliability (this method provides consistent information about RF
      shapes and sizes, which will allow for comparative studies); (f)
      comprehensiveness (this method can scan for RFs over an extensive area of the
      visual field); (g) informativeness (it provides functional quantitative data
      about the RF); and (h) usefulness (this method can map RFs in regions without
      direct retinal inputs, such as the cortical representations of the optic disc and
      of retinal lesions, which should allow for studies of functional connectivity,
      reorganization and neural plasticity). Furthermore, our method allows for precise
      mapping of RFs in a 30 degrees  by 30 degrees  area of the visual field for an
      array of microelectrodes of any size in less than 6 min.

PMID- 24084391
TI  - A comparison of human and machine translation of health promotion materials for
      public health practice: time, costs, and quality.
AB  - CONTEXT: Most local public health departments serve limited English proficiency
      groups but lack sufficient resources to translate the health promotion materials
      that they produce into different languages. Machine translation (MT) with human
      postediting could fill this gap and work toward decreasing health disparities
      among non-English speakers. OBJECTIVES: (1) To identify the time and costs
      associated with human translation (HT) of public health documents, (2) determine
      the time necessary for human postediting of MT, and (3) compare the quality of
      postedited MT and HT. DESIGN: A quality comparison of 25 MT and HT documents was
      performed with public health translators. The public health professionals
      involved were queried about the workflow, costs, and time for HT of 11 English
      public health documents over a 20-month period. Three recently translated
      documents of similar size and topic were then machine translated, the time for
      human postediting was recorded, and a blind quality analysis was performed.
      SETTING: Seattle/King County, Washington. PARTICIPANTS: Public health
      professionals. MAIN OUTCOME MEASURES: (1) Estimated times for various HT tasks;
      (2) observed postediting times for MT documents; (3) actual costs for HT; and (4)
      comparison of quality ratings for HT and MT. RESULTS: Human translation via local
      health department methods took 17 hours to 6 days. While HT postediting words per
      minute ranged from 1.58 to 5.88, MT plus human postediting words per minute
      ranged from 10 to 30. The cost of HT ranged from $130 to $1220; MT required no
      additional costs. A quality comparison by bilingual public health professionals
      showed that MT and HT were equivalently preferred. CONCLUSIONS: MT with human
      postediting can reduce the time and costs of translating public health materials
      while maintaining quality similar to HT. In conjunction with postediting, MT
      could greatly improve the availability of multilingual public health materials.

PMID- 24084392
TI  - The involvement of NLRX1 and NLRP3 in the development of nonalcoholic
      steatohepatitis in mice.
AB  - BACKGROUND: Increasing evidence suggests that innate immunity is involved in the
      development of nonalcoholic fatty liver disease. Nod-like receptors (NLRs) have
      recently been identified as key mediators of inflammatory and immune responses.
      The aim of this article is to explore the correlation of nucleotide-binding
      oligomerization domain (NOD)-like receptor (NLR)X1 and NLRP3 with nonalcoholic
      steatohepatitis (NASH) in mice. METHODS: In our study, a high-fat diet,
      lipopolysaccharides (LPSs), and normal diet were given to C57BL mice to establish
      high fat (HF), HF + LPS, and control groups. Thereafter, serum alanine and
      aspartate aminotransferase (ALT and AST) levels were measured, and NASH severity
      was histologically examined. We measured tumor necrosis factor (TNF)-alpha levels
      by enzyme-linked immunosorbent assay, protein expression by Western blotting, and
      mRNA expression by real-time fluorescent quantitative reverse transcription
      polymerase chain reaction. RESULTS: Levels of ALT and AST were higher in HF + LPS
      mice than in HF mice (p < 0.05). NLRX1 mRNA and protein expression was lower in
      HF and HF + LPS mice than in control mice (p < 0.05). NLRP3 mRNA expression was
      higher in HF and HF + LPS mice than in control mice (p < 0.05). The mRNA and
      protein expression of TNF receptor-associated factor (TRAF)6, interleukin-1beta,
      caspase-1, and apoptosis-associated speck-like protein were significantly higher
      in HF + LPS mice than in control and HF mice; furthermore, mRNA expression was
      higher in HF mice than in control mice (p < 0.05), but protein expression was
      similar. CONCLUSION: NLRX1 and NLRP3 inflammasomes may be important in NASH
      development.

PMID- 24084393
TI  - LncRNA-DQ786227-mediated cell malignant transformation induced by benzo(a)pyrene.
AB  - It has recently been found that the new class of transcripts, long non-coding
      RNAs (lncRNAs), are pervasively transcribed in the genome. LncRNAs are a large
      family of non-coding RNAs and regulate many protein-coding genes. Growing
      evidence indicates that lncRNAs may play an important functional role in cancer
      biology. Emerging data have shown that lncRNAs are closely related to the
      occurrence and development of lung cancer. However, the function and mechanism of
      lncRNAs in lung cancer remain elusive. Here, we investigated the role of a novel
      lncRNA in transformed human bronchial epithelial cells induced by benzo(a)pyrene.
      After establishing the transformed cell model using the BEAS-2B cell line in
      vitro, we found that expression of lncRNA-DQ786227 was high and changed during
      the transformation of BEAS-2B cells. Silencing of lncRNA-DQ786227 expression in
      malignant transformed BEAS-2B cells led to inhibition of cell proliferation and
      colony formation, and increased apoptosis. LncRNA-DQ786227 dramatically promoted
      the ability of BEAS-2B-T cells to form colonies in vitro and develop tumors in
      nude mice. These findings revealed that lncRNA-DQ786227 acts as an oncogene in
      malignantly transformed BEAS-2B cells induced by benzo(a)pyrene. The
      identification of lncRNA could provide new insight into the molecular mechanisms
      of chemical carcinogenesis. 

PMID- 24084394
TI  - Multilevel dynamic systems affecting introduction of HIV/STI prevention
      innovations among Chinese women in sex work establishments.
AB  - Social and public health scientists are increasingly interested in applying
      system dynamics theory to improve understanding and to harness the forces of
      change within complex, multilevel systems that affect community intervention
      implementation, effects, and sustainability. Building a system dynamics model
      based on ethnographic case study has the advantage of using empirically
      documented contextual factors and processes of change in a real-world and real
      time setting that can then be tested in the same and other settings. System
      dynamics modeling offers great promise for addressing persistent problems like
      HIV and other sexually transmitted epidemics, particularly in complex rapidly
      developing countries such as China. We generated a system dynamics model of a
      multilevel intervention we conducted to promote female condoms for HIV/sexually
      transmitted infection (STI) prevention among Chinese women in sex work
      establishments. The model reflects factors and forces affecting the study's
      intervention, implementation, and effects. To build this conceptual model, we
      drew on our experiences and findings from this intensive, longitudinal mixed
      ethnographic and quantitative four-town comparative case study (2007-2012) of the
      sex work establishments, the intervention conducted in them, and factors likely
      to explain variation in process and outcomes in the four towns. Multiple feedback
      loops in the sex work establishments, women's social networks, and the health
      organization responsible for implementing HIV/STI interventions in each town and
      at the town level directly or indirectly influenced the female condom
      intervention. We present the conceptual system dynamics model and discuss how
      further testing in this and other settings can inform future community
      interventions to reduce HIV and STIs. 

PMID- 24084395
TI  - Reconciling statistical and systems science approaches to public health.
AB  - Although systems science has emerged as a set of innovative approaches to study
      complex phenomena, many topically focused researchers including clinicians and
      scientists working in public health are somewhat befuddled by this methodology
      that at times appears to be radically different from analytic methods, such as
      statistical modeling, to which the researchers are accustomed. There also appears
      to be conflicts between complex systems approaches and traditional statistical
      methodologies, both in terms of their underlying strategies and the languages
      they use. We argue that the conflicts are resolvable, and the sooner the better
      for the field. In this article, we show how statistical and systems science
      approaches can be reconciled, and how together they can advance solutions to
      complex problems. We do this by comparing the methods within a theoretical
      framework based on the work of population biologist Richard Levins. We present
      different types of models as representing different tradeoffs among the four
      desiderata of generality, realism, fit, and precision. 

PMID- 24084396
TI  - Implications of network structure on public health collaboratives.
AB  - Interorganizational collaboration is an essential function of public health
      agencies. These partnerships form social networks that involve diverse types of
      partners and varying levels of interaction. Such collaborations are widely
      accepted and encouraged, yet very little comparative research exists on how
      public health partnerships develop and evolve, specifically in terms of how
      subsequent network structures are linked to outcomes. A systems science approach,
      that is, one that considers the interdependencies and nested features of
      networks, provides the appropriate methods to examine the complex nature of these
      networks. Applying Mays and Scutchfields's categorization of "structural
      signatures" (breadth, density, and centralization), this research examines how
      network structure influences the outcomes of public health collaboratives.
      Secondary data from the Program to Analyze, Record, and Track Networks to Enhance
      Relationships (www.partnertool.net) data set are analyzed. This data set consists
      of dyadic (N = 12,355), organizational (N = 2,486), and whole network (N = 99)
      data from public health collaborations around the United States. Network data are
      used to calculate structural signatures and weighted least squares regression is
      used to examine how network structures can predict selected intermediary outcomes
      (resource contributions, overall value and trust rankings, and outcomes) in
      public health collaboratives. Our findings suggest that network structure may
      have an influence on collaborative-related outcomes. The structural signature
      that had the most significant relationship to outcomes was density, with higher
      density indicating more positive outcomes. Also significant was the finding that
      more breadth creates new challenges such as difficulty in reaching consensus and
      creating ties with other members. However, assumptions that these structural
      components lead to improved outcomes for public health collaboratives may be
      slightly premature. Implications of these findings for research and practice are
      discussed. 

PMID- 24084397
TI  - Social networks and smoking: exploring the effects of peer influence and smoker
      popularity through simulations.
AB  - Adolescent smoking and friendship networks are related in many ways that can
      amplify smoking prevalence. Understanding and developing interventions within
      such a complex system requires new analytic approaches. We draw on recent
      advances in dynamic network modeling to develop a technique that explores the
      implications of various intervention strategies targeted toward micro-level
      processes. Our approach begins by estimating a stochastic actor-based model using
      data from one school in the National Longitudinal Study of Adolescent Health. The
      model provides estimates of several factors predicting friendship ties and
      smoking behavior. We then use estimated model parameters to simulate the
      coevolution of friendship and smoking behavior under potential intervention
      scenarios. Namely, we manipulate the strength of peer influence on smoking and
      the popularity of smokers relative to nonsmokers. We measure how these
      manipulations affect smoking prevalence, smoking initiation, and smoking
      cessation. Results indicate that both peer influence and smoking-based popularity
      affect smoking behavior and that their joint effects are nonlinear. This study
      demonstrates how a simulation-based approach can be used to explore alternative
      scenarios that may be achievable through intervention efforts and offers new
      hypotheses about the association between friendship and smoking. 

PMID- 24084398
TI  - Network influences on dissemination of evidence-based guidelines in state tobacco
      control programs.
AB  - Little is known regarding the social network relationships that influence
      dissemination of evidence-based public health practices and policies. In public
      health, it is critical that evidence-based guidelines, such as the Centers for
      Disease Control and Prevention's Best Practices for Comprehensive Tobacco Control
      Programs, are effectively and efficiently disseminated to intended stakeholders.
      To determine the organizational and network predictors of dissemination among
      state tobacco control programs, interviews with members of tobacco control
      networks across eight states were conducted between August 2009 and September
      2010. Measures included partner attributes (e.g., agency type) and relationships
      among network members (frequency of contact, extent of collaboration, and
      dissemination of Best Practices). Exponential random graph modeling was used to
      examine attribute and structural predictors of collaboration and dissemination
      among partners in each network. Although density and centralization of
      dissemination ties varied across states, network analyses revealed a consistent
      prediction pattern across all eight states. State tobacco control dissemination
      networks were less dense but more centralized compared with organizational
      contact and collaboration networks. Tobacco control partners in each state were
      more likely to disseminate the Best Practices guidelines if they also had
      existing contact and collaboration relationships with one another. Evidence-based
      guidelines in public health need to be efficiently and broadly disseminated if we
      hope to translate science into practice. This study suggests that funders,
      advocacy groups, and public health agencies can take advantage of existing public
      health organizational relationships to support the communication and
      dissemination of evidence-based practices and policies. 

PMID- 24084399
TI  - Interorganizational relationships in the Heart and Stroke Foundation's Spark
      Together for Healthy KidsTM: insights from using network analysis.
AB  - The Heart and Stroke Foundation's Spark Together for Healthy KidsTM (Spark) is a
      multiyear initiative in Ontario, Canada, that takes a population approach to
      obesity prevention. It focuses on creating healthy environments by improving
      access to healthy foods and physical activity, with an emphasis on strengthening
      the advocacy capacity of organizations and citizens. Consistent with the
      complexity of the intervention, the evaluation of Spark applied systems concepts
      and methods to test the utility of network analysis as a method for evaluation,
      and to inform collaborations of organizations involved in programs and advocacy.
      Relationships among organizations from different sectors and jurisdictional
      levels with a focus on school community environments were of particular interest.
      Interorganizational network analysis was used to understand these relationships,
      including the role of the Heart and Stroke Foundation. Findings revealed a niche
      brokering role for the Heart and Stroke Foundation and other provincial and
      national organizations, and the importance of these brokers for engaging local
      and regional organizations. Findings also reinforced the importance of a mixed
      methods approach to network analysis, and the potential value of the analysis for
      scientific and practical purposes. 

PMID- 24084401
TI  - Opening a window on systems science research in health promotion and public
      health.

PMID- 24084400
TI  - Exploring behavioral markers of long-term physical activity maintenance: a case
      study of system identification modeling within a behavioral intervention.
AB  - Efficacious interventions to promote long-term maintenance of physical activity
      are not well understood. Engineers have developed methods to create dynamical
      system models for modeling idiographic (i.e., within-person) relationships within
      systems. In behavioral research, dynamical systems modeling may assist in
      decomposing intervention effects and identifying key behavioral patterns that may
      foster behavioral maintenance. The Active Adult Mentoring Program was a 16-week
      randomized controlled trial of a group-based, peer-delivered physical activity
      intervention targeting older adults. Time-intensive (i.e., daily) physical
      activity reports were collected throughout the intervention. We explored
      differential patterns of behavior among participants who received the active
      intervention (N = 34; 88% women, 64.1 +/- 8.3 years of age) and either maintained
      150 minutes/week of moderate to vigorous intensity physical activity (MVPA; n =
      10) or did not (n = 24) at 18 months following the intervention period. We used
      dynamical systems modeling to explore whether key intervention components (i.e.,
      self-monitoring, access to an exercise facility, behavioral initiation training,
      behavioral maintenance training) and theoretically plausible behavioral
      covariates (i.e., indoor vs. outdoor activity) predicted differential patterns of
      behavior among maintainers and nonmaintainers. We found that maintainers took
      longer to reach a steady-state of MVPA. At week 10 of the intervention,
      nonmaintainers began to drop whereas maintainers increased MVPA. Self-monitoring,
      behavioral initiation training, percentage of outdoor activity, and behavioral
      maintenance training, but not access to an exercise facility, were key variables
      that explained patterns of change among maintainers. Future studies should be
      conducted to systematically explore these concepts within a priori idiographic
      (i.e., N-of-1) experimental designs. 

PMID- 24084402
TI  - Modeling social dimensions of oral health among older adults in urban
      environments.
AB  - In both developed and developing countries, population aging has attained
      unprecedented levels. Public health strategies to deliver services in community
      based settings are key to enhancing the utilization of preventive care and
      reducing costs for this segment of the population. Motivated by concerns of
      inadequate access to oral health care by older adults in urban environments, this
      article presents a portfolio of systems science models that have been developed
      on the basis of observations from the ElderSmile preventive screening program
      operated in northern Manhattan, New York City, by the Columbia University College
      of Dental Medicine. Using the methodology of system dynamics, models are
      developed to explore how interpersonal relationships influence older adults'
      participation in oral health promotion. Feedback mechanisms involving word of
      mouth about preventive screening opportunities are represented in relation to
      stocks that change continuously via flows, as well as agents whose states of
      health care utilization change discretely using stochastic transitions. Agent
      based implementations illustrate how social networks and geographic information
      systems are integrated into dynamic models to reflect heterogeneous and proximity
      based patterns of communication and participation in the ElderSmile program. The
      systems science approach builds shared knowledge among an interdisciplinary
      research team about the dynamics of access to opportunities for oral health
      promotion. Using "what if" scenarios to model the effects of program enhancements
      and policy changes, resources may be effectively leveraged to improve access to
      preventive and treatment services. Furthermore, since oral health and general
      health are inextricably linked, the integration of services may improve outcomes
      and lower costs. 

PMID- 24084403
TI  - Modeling the impact of simulated educational interventions on the use and abuse
      of pharmaceutical opioids in the United States: a report on initial efforts.
AB  - Three educational interventions were simulated in a system dynamics model of the
      medical use, trafficking, and nonmedical use of pharmaceutical opioids. The study
      relied on secondary data obtained in the literature for the period of 1995 to
      2008 as well as expert panel recommendations regarding model parameters and
      structure. The behavior of the resulting systems-level model was tested for fit
      against reference behavior data. After the base model was tested, logic to
      represent three educational interventions was added and the impact of each
      intervention on simulated overdose deaths was evaluated over a 7-year evaluation
      period, 2008 to 2015. Principal findings were that a prescriber education
      intervention not only reduced total overdose deaths in the model but also reduced
      the total number of persons who receive opioid analgesic therapy, medical user
      education not only reduced overdose deaths among medical users but also resulted
      in increased deaths from nonmedical use, and a "popularity" intervention sharply
      reduced overdose deaths among nonmedical users while having no effect on medical
      use. System dynamics modeling shows promise for evaluating potential
      interventions to ameliorate the adverse outcomes associated with the complex
      system surrounding the use of opioid analgesics to treat pain. 

PMID- 24084405
TI  - Evaluating the effectiveness of contact tracing on tuberculosis outcomes in
      Saskatchewan using individual-based modeling.
AB  - Tuberculosis (TB) is a potentially fatal disease spread by an airborne pathogen
      infecting approximately one third of the globe. For decades, contact tracing (CT)
      has served a key role in the control of TB and many other notifiable communicable
      diseases. Unfortunately, CT is a labor-intensive and time-consuming process and
      is often conducted by a small and overworked nursing staff. To help improve the
      effectiveness of CT, we introduce a detailed, individual-based model of CT for
      the Canadian province of Saskatchewan. The model captures the detailed operation
      of TB CT, including loss to follow-up, and prophylactic and case treatment. This
      representation is used to assess the impact on active TB cases and TB infection
      prevalence of differential scoping, speed, prioritization of the CT process, and
      reduced loss to follow-up. Scenario results are broadly consistent with--but
      provide many additional insights beyond--our previously reported findings using
      an aggregate model. In the context of a stylized northern community, findings
      suggest that age- and ethnicity-prioritized schemes could improve CT
      effectiveness compared to unprioritized schemes by dramatically reducing TB
      infection and preventing on average roughly 11% (p < .0001) of active TB cases
      over a period of 20 years. Reducing loss to follow-up to 10% could yield 5.4% (p
      = .02) TB cases prevented on average with lower prevalence of TB infection, but
      improving the CT speed does not yield significant improvement in TB outcomes.
      Finally, although the work emphasized the value of social network analysis, we
      found that caution should be exercised in directly translating social network
      analysis-observed associations into prioritization recommendations.

PMID- 24084404
TI  - Dynamic simulation of crime perpetration and reporting to examine community
      intervention strategies.
AB  - OBJECTIVE: To develop a conceptual computational agent-based model (ABM) to
      explore community-wide versus spatially focused crime reporting interventions to
      reduce community crime perpetrated by youth. METHOD: Agents within the model
      represent individual residents and interact on a two-dimensional grid
      representing an abstract nonempirically grounded community setting. Juvenile
      agents are assigned initial random probabilities of perpetrating a crime and
      adults are assigned random probabilities of witnessing and reporting crimes. The
      agents' behavioral probabilities modify depending on the individual's experience
      with criminal behavior and punishment, and exposure to community crime
      interventions. Cost-effectiveness analyses assessed the impact of activating
      different percentages of adults to increase reporting and reduce community crime
      activity. Community-wide interventions were compared with spatially focused
      interventions, in which activated adults were focused in areas of highest crime
      prevalence. RESULTS: The ABM suggests that both community-wide and spatially
      focused interventions can be effective in reducing overall offenses, but their
      relative effectiveness may depend on the intensity and cost of the interventions.
      Although spatially focused intervention yielded localized reductions in crimes,
      such interventions were shown to move crime to nearby communities. Community-wide
      interventions can achieve larger reductions in overall community crime offenses
      than spatially focused interventions, as long as sufficient resources are
      available. CONCLUSION: The ABM demonstrates that community-wide and spatially
      focused crime strategies produce unique intervention dynamics influencing
      juvenile crime behaviors through the decisions and actions of community adults.
      It shows how such models might be used to investigate community-supported crime
      intervention programs by integrating community input and expertise and provides a
      simulated setting for assessing dimensions of cost comparison and intervention
      effect sustainability. ABM illustrates how intervention models might be used to
      investigate community-supported crime intervention programs.

PMID- 24084406
TI  - Systems science: a good investment for the public's health.
AB  - This supplement of Health Education & Behavior showcases the current state of the
      field of systems science applications in health promotion and public health.
      Behind this work lies a steady stream of public dollars at the federal level.
      This perspective details nearly a decade of investment by the National Institutes
      of Health's Office of Behavioral and Social Sciences Research. These investments
      have included funding opportunity announcements, training programs, developing
      resources for researchers, cross-disciplinary fertilization, and publication.
      While much progress has been made, continuing investment is needed in the future
      to ensure the viability and sustainability of this young but increasingly
      important field. 

PMID- 24084407
TI  - Outcomes of a head and neck cancer screening clinic.
AB  - OBJECTIVE: To describe an institutional experience conducting an annual free head
      and neck (H&N) cancer screening clinic. Specific aims included: (1) identifying
      factors predicting which individuals will have findings suspicious for
      malignancy; and (2) evaluating potential barriers to subsequent follow-up among
      patients with suspicious findings. MATERIALS AND METHODS: This retrospective
      cohort study involved individuals presenting to an annual H&N cancer screening
      clinic (2001-2012). Original screening clinic data and electronic medical records
      were reviewed. Descriptive and comparative statistics were utilized in order to
      address the study aims. RESULTS: Of 1573 participants, 325 (21%) had abnormal
      findings on screening, of which 183 (12%) had findings suspicious for cancer. No
      demographic factors predicted a suspicion for cancer. The presence of patient
      reported symptoms (16% vs. 8%; p<0.001) were significantly associated with a
      suspicion for cancer. Only 20% of individuals with a suspicion for cancer
      returned to our institution for recommended follow-up. Patients who did not
      complain of symptoms were less likely to return for follow-up (2% vs. 36%;
      p<0.001). Of the patients who returned for follow-up evaluation, malignancies
      were diagnosed in three patients. CONCLUSION: Few individuals presenting to a H&N
      cancer screening clinic will have a malignancy detected, and barriers may
      influence patients' likelihood to present for subsequent evaluation. Due to self
      selection among patients presenting for screening, traditional risk factors may
      not be associated with the likelihood of detecting a suspicion for H&N cancer.
      Head and neck cancer screening clinics should thus target patients at high risk,
      and attempt to ensure appropriate follow-up thereafter.

PMID- 24084408
TI  - Role of oxidative stress in malignant transformation of oral lichen planus.

PMID- 24084409
TI  - Establishing standard performance measures for adult brain tumor patients: a
      Nationwide Inpatient Sample database study.
AB  - BACKGROUND: The Agency for Healthcare Research and Quality (AHRQ) patient safety
      indicators (PSIs) and the Centers for Medicare and Medicaid Services (CMS)
      hospital acquired conditions (HACs) are used to evaluate the safety and quality
      of health care. We determined the incidence rates of PSIs and HACs among brain
      tumor patients in the Nationwide Inpatient Sample database (NIS). METHODS: We
      queried the NIS for all hospitalizations involving a brain tumor. We determined
      the incidence rates of various PSIs and HACs among these patients by searching
      the hospital records for codes in the International Classification of Diseases,
      9th Revision indicating each PSI or HAC. RESULTS: Among the 501 908
      hospitalizations involving a brain tumor in the NIS, there were 102 046
      occurrences of an AHRQ PSI, with 16% of patients experiencing one or more AHRQ
      PSI. Among brain tumor patients treated without surgery, 17.2% experienced >= 1
      PSI. Among brain tumor patients treated with surgery, 9.8% experienced >= 1 PSI.
      The most common PSIs were postoperative respiratory failure, deep vein
      thrombosis, and sepsis. The total number of HACs associated with brain tumor
      patients was 13 778, with 2.63% of patients experiencing >=1 HAC. Among brain
      tumor patients treated without surgery, 3.0% experienced >= 1 HAC. Among brain
      tumor patients treated with surgery, 7.4% experienced >= 1 HAC. The most common
      HACs were falls and trauma and pressure ulcers. Increasing comorbidity score was
      associated with increased likelihood of almost all PSIs and HACs. CONCLUSION:
      These data may be used to determine individual institutional improvements or
      success by comparison.

PMID- 24084410
TI  - Invasion patterns in brain metastases of solid cancers.
AB  - BACKGROUND: Brain metastases are generally considered to be well demarcated from
      the surrounding brain parenchyma, although infiltrative growth patterns have been
      observed. We systemically investigated infiltration patterns and expression of
      adhesion molecules in a large and well-defined series of autopsy cases of brain
      metastases. METHODS: Ninety-seven autopsy specimens from 57 brain metastasis
      patients (primary tumor: 27 lung cancer, 6 breast cancer, 8 melanoma, 2
      colorectal cancer, 1 kidney cancer, and 13 other) were evaluated for patterns of
      invasion into surrounding brain parenchyma. Expression of integrins alphav;
      cytoplasmic beta3, alphavbeta3, alphavbeta5, alphavbeta6, and alphavbeta8; and of
      E and N cadherin were evaluated using immunohistochemistry. RESULTS: Three main
      invasion patterns were seen: well-demarcated growth (29/57, 51%), vascular co
      option (10/57, 18%), and diffuse infiltration (18/57, 32%). There was no
      statistically significant association of invasion pattern with primary tumor
      type, although vascular co-option was most common in melanoma brain metastases
      (4/10). Invasion patterns of different brain metastases of the same patient were
      highly concordant (P < .001, chi-square test). Distance of infiltration from the
      main tumor mass ranged from 12.5 um to 450 um (median 56.2 um) and was not
      significantly different between the vascular co-option and the diffuse
      infiltration groups. Levels of alphavbeta6 were significantly higher in the well
      demarcated group than in the vascular co-option and the diffuse infiltration
      groups (P = .033, Kruskal-Wallis test). Expression of alphavbeta5 in tumor cells
      was higher in brain metastasis lesions previously treated with stereotactic
      radiosurgery (P = .034, chi-square test). CONCLUSIONS: Distinct invasion patterns
      of brain metastases into the brain parenchyma are not specific for primary tumor
      types, seem to be influenced by expression of alphav integrin complexes, and may
      help to guide clinical decision-making.

PMID- 24084411
TI  - Effect of 16 pure hydrocarbons on the stabilization and lysis of fish
      (mudskipper: Boleophthalmus dussumieri) erythrocytes.
AB  - The in vitro effects of polycyclic aromatic hydrocarbons (PAHs) on erythrocyte
      membrane stability of the mudskipper (i.e., Boleophthalmus dussumieri) were
      tested by using field concentrations, acute and chronic potency divisor
      concentrations. This was achieved by studying their lytic or antilytic effects on
      fish erythrocytes in critical hypotonic saline media. The interaction of PAHs
      acute potency divisor concentrations with mudskipper erythrocyte causes dramatic
      changes in the structure of the membrane. A significant difference (p<0.05) was
      found between the control and treatment groups of mudskipper erythrocyte exposed
      to acute potency divisor concentrations. No significant difference (p>0.05) was
      observed between the control and the treatment groups of mudskipper erythrocyte
      exposed to field concentrations. The results showed that chronic potency divisor
      concentrations of PAHs protect mudskipper erythrocyte against osmotic hemolysis.
      Our results could be extended to the use of Erythrocyte Osmotic Fragility (EOF)
      test as a biochemical marker of membrane toxicity in marine pollution
      biomonitoring. However, results showed that membrane stability is not an
      appropriate biomarker for PAHs pollution after short exposure duration. 

PMID- 24084412
TI  - Eight papers from UEMS-PRM Section Professional Practice Committee.

PMID- 24084413
TI  - Generalised and regional soft tissue pain syndromes. The role of physical and
      rehabilitation medicine physicians. The European perspective based on the best
      evidence. A paper by the UEMS-PRM Section Professional Practice Committee.
AB  - One of the objectives of the Professional Practice Committee (PPC) of the
      Physical and Rehabilitation Medicine (PRM) Section of the Union of European
      Medical Specialists (UEMS) is the development of the field of competence of PRM
      physicians in Europe. To achieve this objective, UEMS PRM Section PPC has adopted
      a systematic action plan of preparing a series of papers describing the role of
      PRM physicians in a number of disabling health conditions, based on the evidence
      of effectiveness of PRM interventions. Generalised and regional soft tissue pain
      syndromes constitute a major problem leading to loss of function and disability,
      resulting in enormous societal burden. The aim of this paper is to describe the
      unique role of PRM physicians in the management of these disabling conditions
      that require not only pharmacological interventions but also a holistic approach
      including the consideration of body functions, activities and participation as
      well as contextual factors as described in the ICF. Evidence-based effective PRM
      interventions include exercise and multicomponent treatment including a
      psychotherapeutic intervention such as cognitive behavioural therapy (CBT) in
      addition to exercise, the latter based on strong evidence for reducing pain and
      improving quality of life in fibromyalgia syndrome (FMS). Balneotherapy,
      meditative movement therapies, and acupuncture have also been shown as
      efficacious in improving symptoms in FMS. Emerging evidence suggests the use of
      transcranial magnetic or direct current stimulation (rTMS or tDCS) in FMS
      patients with intractable pain not alleviated by other interventions. Graded
      exercise therapy and CBT are evidence-based options for chronic fatigue syndrome.
      The use of some physical modalities and manipulation for myofascial pain syndrome
      is also supported by evidence. As for complex regional pain syndrome (CRPS),
      strong evidence exists for rTMS and graded motor imagery as well as moderate
      evidence for mirror therapy. Interventional techniques such as blocks and spinal
      cord stimulation may also be considered for CRPS based on varying levels of
      evidence. PRM physicians' functioning oriented approaches on the assessment and
      management, adopting the ICF as a reference, may well meet the needs of patients
      with soft tissue pain syndromes, the common problems for whom are loss of
      function and impaired quality of life. Available evidence for the effectiveness
      of PRM interventions serves as the basis for the explicit role of PRM specialists
      in the management of these health conditions. 

PMID- 24084414
TI  - Inflammatory arthritis. The role of physical and rehabilitation medicine
      physicians. The European perspective based on the best evidence. A paper by the
      UEMS-PRM Section Professional Practice Committee.
AB  - One of the objectives of the Professional Practice Committee (PPC) of the
      Physical and Rehabilitation Medicine (PRM) Section of the Union of European
      Medical Specialists (UEMS) is the development of the field of competence of PRM
      physicians in Europe. To achieve this objective, UEMS PRM Section PPC has adopted
      a systematic action plan of preparing a series of papers describing the role of
      PRM physicians in a number of disabling health conditions, based on the evidence
      of effectiveness of the physical and rehabilitation medicine interventions.
      Inflammatory arthritis is a major cause of disability with an important economic
      burden in society. The goals in the management of inflammatory arthritis are to
      control pain and disease activity, prevent joint damage, protect and enhance
      function and improve quality of life. This paper aims to define the role of PRM
      physicians in people with inflammatory arthritis. PRM interventions imply non
      pharmacological treatments which include patient education for joint protection,
      energy conservation and self-management techniques, exercise therapy, physical
      modalities, orthoses/assistive devices and balneotherapy. Therapeutic patient
      education and exercises are the cornerstones of therapy with strong evidence of
      their effectiveness to improve function. Physical modalities are primarily used
      to decrease pain and stiffness whereas orthoses/assistive devices are usually
      prescribed to enhance activities and participation. PRM physicians have distinct
      roles in the management of people with inflammatory arthritis such that they
      effectively organise and supervise the PRM program in the context of
      interdisciplinary team work. Their role starts with a comprehensive assessment of
      patient's functioning based on the International Classification of Functioning
      Disability and Health (ICF) as the framework. In the light of this assessment,
      appropriate PRM interventions individualised for the patient are administered.
      Future research and actions regarding the role of PRM in inflammatory arthritis
      should target access to care, updates on the use and effectiveness of physical
      modalities, orthoses/assistive devices, and standardization of therapeutic
      patient education programs. 

PMID- 24084415
TI  - Osteoporosis. The role of physical and rehabilitation medicine physicians. The
      European perspective based on the best evidence. A paper by the UEMS-PRM Section
      Professional Practice Committee.
AB  - One of the objectives of the Professional Practice Committee (PPC) of the
      Physical and Rehabilitation Medicine (PRM) Section of the Union of European
      Medical Specialists (UEMS) is the development of the field of competence of PRM
      physicians in Europe. To achieve this objective, UEMS PRM Section PPC has adopted
      a systematic action plan of preparing a series of papers describing the role of
      PRM physicians in a number of disabling health conditions, based on the evidence
      of effectiveness of PRM interventions. A wide range of health conditions treated
      by PRM specialists carries the risk of osteoporosis (OP). The consequences of OP
      may be associated with significant disability. The aim of this paper is: to
      define the role of PRM physicians in the prevention and management of OP, to
      describe the needs of people with OP in relation to rehabilitation strategy, and
      to highlight why and how PRM physicians should be involved in the diagnosis and
      management of OP. PRM physicians may intervene in the prevention of and risk
      factor assessment for OP, falls and fractures along with other assessments of
      functioning and of quality of life. In addition, they are involved in diagnosis
      and in both pharmacological and nonpharmacological treatment of OP. From a
      specific PRM perspective based on the International Classification of
      Functioning, Disability and Health (ICF), there is an important role in
      optimizing functioning and promoting "activities and participation", including
      interventions associated with environmental factors for people with OP or
      osteoporotic fractures. Evidence suggests that a large number of interventions
      within the scope of PRM that range from preventive strategies (including
      education and self management and most importantly exercise) to pain management
      strategies and spinal orthoses or hip protectors may be effective in the
      prevention and/or management of OP and its sequelae. Competencies and aptitudes
      of PRM specialists, focusing especially on functioning while providing care over
      the whole course of a health condition from the hospital to the community, may
      well place them in the management of OP. Evidence-based effective PRM
      interventions further warrant the role of PRM physicians in the management of OP.

PMID- 24084417
TI  - Systematic reviews of physical and rehabilitation medicine Cochrane contents.
      Introduction.

PMID- 24084416
TI  - Osteoarthritis. The role of physical and rehabilitation medicine physicians. The
      European perspective based on the best evidence. A paper by the UEMS-PRM Section
      Professional Practice Committee.
AB  - One of the objectives of the Professional Practice Committee (PPC) of the
      Physical and Rehabilitation Medicine (PRM) Section of the Union of European
      Medical Specialists (UEMS) is the development of the field of competence of PRM
      physicians in Europe. To achieve this objective, UEMS PRM Section PPC has adopted
      a systematic action plan of preparing a series of papers describing the role of
      PRM physicians in a number of disabling health conditions, based on the evidence
      of effectiveness of the PRM interventions. Osteoarthritis (OA) is the most common
      joint disorder and the major cause of musculoskeletal pain and limited mobility
      in the elderly in the world. Therefore, proper management of persons with OA is
      of substantial importance. The goal of OA management is to reduce the impact of
      OA on the individual by reducing pain and improving function, activities and
      participation. The aim of this paper is to descibe the explicit role of PRM
      physicians in providing management for persons with OA. The optimal management of
      OA requires the combination of both non-pharmacological and pharmacological
      approaches, an issue most of the main guidelines on the evidence-based management
      of OA share in common. There is good level of evidence about the effectiveness of
      PRM interventions in the management of OA: high level of evidence about the
      effect of education, weight reduction and exercise and growing evidence about the
      effectiveness of physical agent modalities. PRM specialists are involved not only
      in diagnosis and medical and physical treatments of OA, but, as a rehabilitation
      strategy, they also deal with the problems of the person focusing on the
      improvement of all components of human functioning as defined in the ICF
      including personal and environmental factors with a holistic approach. ICF core
      sets for OA serve as excellent models for directing proper assessments as well as
      targeting interventions. PRM specialists well meet the needs of people with OA
      from the early stages of the disease to the stage of disability that could cause
      activity limitations and participation restrictions. In conclusion, PRM
      specialists can make substantial contributions to providing management of OA in
      order to improve the functioning of individuals with OA from both personal and
      societal perspective. 

PMID- 24084418
TI  - Systematic reviews of physical and rehabilitation medicine Cochrane contents.
      Part 1. Disabilities due to spinal disorders and pain syndromes in adults.
AB  - BACKGROUND: This article is the first in a series presenting the strongest
      published evidence for physical and rehabilitation medicine (PRM) to date coming
      from the Cochrane Collaboration. The intent of the series is to stimulate ideas
      for reviews and research in neglected areas of PRM. AIM: To systematically review
      the rehabilitation contents of the Cochrane Collaboration on disabilities due to
      spinal disorders or pain syndromes in adults. METHODS: The Cochrane Database of
      Systematic Reviews was searched at the end of June 2013 for articles relevant for
      PRM about disabilities resulting from spinal disorders or pain syndromes in
      adults. Retrieved papers were classified according to the PRM approach: active
      therapies, which require active participation by patients to achieve treatment
      goals, and passive treatments, which rely on the application of external forces.
      The quality of the reviews was checked against the AMSTAR checklist. RESULTS:
      Reviews on spinal disorders or pain syndromes were found in the Cochrane Back
      Group (CBG) and in the Pain, Palliative and Supportive Care Group (CPPSCG).
      Thirty-eight (42.8%) of 89 Cochrane reviews in the CBG and 7 (2.4%) of 293
      Cochrane reviews in the CPPSCG were included. All were of high quality (range, 8
      11 points out of 11 on the AMSTAR checklist). The contents of the reviews are
      given in detail. CONCLUSION: This review presents an overview of the current
      evidence for PRM in the treatment of disabilities due to spinal disorders or pain
      syndromes in adults. Within PRM there is ample space for research in the Cochrane
      Collaboration and for producing original studies (randomized controlled trials
      [RCTs]). CLINICAL REHABILITATION IMPACT: To apply evidence-based clinical
      practice, clinicians must be familiar with the current best evidence.

PMID- 24084419
TI  - [Challenge of social reintegration after a first-episode psychosis].
AB  - One of the main issues of early intervention in first-episode psychosis is to
      prevent social exclusion, or at least to seek to reduce it as soon as possible.
      The aim is not only symptom remission and relapse prevention, it is also to
      optimize the social and functional outcome of the illness. Social exclusion is
      not only one the disabling consequences of the illness, it is also, due to a
      negative circularity, an aggravating factor. Therefore, alongside the healthcare
      strategy aiming at the remission and relapse prevention, it will be useful to set
      up, at an early stage, a strategy aiming at maintaining or restoring social
      inclusion, and more generally to support the social recovery. We will specify the
      factors conditioning such prospects for recovery, and the variety of measures to
      support this strategy. 

PMID- 24084420
TI  - [Psychoeducation of patients and their family members during episode psychosis].
AB  - The concept of psychoeducation is close to the concept of therapeutic education
      and refers to a kind of education intervention targeting people with a mental
      health condition. In the framework of psychosis, psychoeducation can be offered
      to patients, family members or both. The efficacy of patient psychoeducation on
      treatment adherence or social functioning is well-established but only if the
      family benefits of a joint psychoeducational intervention. Family
      psychoeducation, even without patient psychoeducation has proven efficacy in
      reducing relapse rate. This reduction is of the same order of magnitude as that
      obtained with an antipsychotic medication. 

PMID- 24084421
TI  - [Cognitive behavior therapy after first-episodes psychosis].
AB  - Cognitive behavior therapy (CBT) is recommended for the treatment of first
      episode psychosis (FEP) patients. It can be offered in acute state or during the
      remission of the episode. Up to date, effects of CBT have been examined in
      several controlled and randomized trials in FEP. Combined with antipsychotic
      medications, results have demonstrated that CBT decreases positive psychotic
      symptoms, enhances quality of live, self-esteem and insight, and diminishes the
      intensity of comorbide symptoms, such as trauma or suicide behavior. CBT might be
      particularly efficient in individuals wishing to reintegrate premorbide
      functioning and those with low duration of untreated psychosis. Despite these
      encouraging results, psychosis orientated CBT are underused in France. The
      validation of group CBT specifically designed for FEP should enhance the range of
      patients receiving this treatment. Moreover, early CBT interventions for people
      at ultra high-risk for psychosis and assertive community treatments should be
      developed.

PMID- 24084422
TI  - [Guidelines on long-acting injectable atypical antipsychotics for first-episode
      schizophrenia].
AB  - The current review raises the question of the place of long-acting injectable
      (LAI) atypical antipsychotics for the treatment of first-episode schizophrenia in
      current and future guidelines. After exposing the different points of view
      adopted in the former, the author presents the clinical trials conducted with LAI
      atypicals in this indication, as well as the surveys related to
      psychiatrists'opinion regarding the use of these drugs in early schizophrenia.
      Pros and cons of this therapeutic option are discussed and suggestions are made
      for further guidelines. 

PMID- 24084423
TI  - [The first psychotic episode].

PMID- 24084424
TI  - [The first psychotic episode].

PMID- 24084425
TI  - [First-episodes psychosis: clinical and epidemiological news].
AB  - In the context of the development of early intervention for first-episode
      psychosis, this manuscript reviews new data with respect to its incidence, risk
      factors and evolution. Annual incidence of non-affective psychosis appeared to be
      between 14 and 30/100,000 in people aged 18-64. Incidence decreases with age and
      is twice higher in men than in women. There is an interaction between age and
      gender; the risk of psychosis decreases with age faster in men than in women.
      Thus, for schizophrenia, incidence rate is twice higher in men under 45 year-old
      and similar in both genders after. There is evidence that genetic and
      environmental factors may cause enduring liability to psychotic disorder, and, in
      addition, that genes and environment may interact synergistically. Some
      environmental factors have been identified; they concern foetal life, childhood
      or adolescence and may be conceptualized at the individual or the contextual
      level. The definition of recent onset psychosis may be based on duration of
      psychosis, between two and five years. Its development is identified through the
      occurrence of major psychotic symptoms, such as positive, negative symptomatology
      or disorganization, and impairment of social functioning. The types and patterns
      of occurrence and of evolution of psychotic symptoms have a prognostic impact. A
      long duration of untreated psychosis impacts symptomatology. It is associated
      with less severe positive symptoms at baseline and more severe after three years,
      insidious onset, male gender, early onset, and diagnosis of schizophrenia. Recent
      onset psychosis is often associated with comorbidities, such as depression,
      anxiety disorders, suicidal behaviours, and addiction. Symptomatic remission
      rates are found between 25 and 60%. Symptomatic and functional remissions favour
      each other. A third to half of patients is active, employed or students. Symptoms
      and evolution are various in studies, probably corresponding to various patho
      physiological mechanisms.

PMID- 24084426
TI  - [Relapse: causes and consequences].
AB  - Relapse after a first episode of schizophrenia is the recurrence of acute
      symptoms after a period of partial or complete remission. Due to its variable
      aspects, there is no operational definition of relapse able to modelise the
      outcome of schizophrenia and measure how the treatment modifies the disease.
      Follow-up studies based on proxys such as hospital admission revealed that 7 of
      10 patients relapsed after a first episode of schizophrenia. The effectiveness of
      antipsychotic medications on relapse prevention has been widely demonstrated.
      Recent studies claim for the advantages of atypical over first generation
      antipsychotic medication. Non-adherence to antipsychotic represents with
      addictions the main causes of relapse long before some non-consensual factors
      such as premorbid functioning, duration of untreated psychosis and associated
      personality disorders. The consequences of relapse are multiple, psychological,
      biological and social. Pharmaco-clinical studies have demonstrated that the
      treatment response decreases with each relapse. Relapse, even the first one, will
      contribute to worsen the outcome of the disease and reduce the capacity in
      general functionning. Accepting the idea of continuing treatment is a complex
      decision in which the psychiatrist plays a central role besides patients and
      their families. The development of integrated actions on modifiable risk factors
      such as psychosocial support, addictive comorbidities, access to care and the
      therapeutic alliance should be promoted. Relapse prevention is a major goal of
      the treatment of first-episode schizophrenia. It is based on adherence to the
      maintenance treatment, identification of prodromes, family active information and
      patient therapeutical education.

PMID- 24084427
TI  - [First-episode psychosis, cognitive difficulties and remediation].
AB  - Cognitive difficulties are a core feature of schizophrenia. They are frequent,
      severe, and clearly associated with functional disabilities. They have been
      explored during different phases of the disease, but what we know essentially
      concerns the chronic period in middle-age patients. In this article we will
      specifically focus on cognition at the time of first episode. First episode is a
      key life period, occurring while social demands are increasing and more complex
      on the one hand, and while there are important changes in structural and
      functional cerebral anatomy on the other hand. Exploring cognitive difficulties
      at the time of first episode offers the opportunity to better know their time
      course, to avoid interpretative difficulties due to the chronicity of the disease
      and its treatments, and to develop early therapeutics in order to improve
      outcome. Cognitive difficulties are clearly present at the time of first episode;
      their nature and severity appear similar to those observed in more chronic
      patients. Therefore, they cannot be entirely explained by treatments,
      hospitalizations or chronicity, and appear more as an intrinsic feature of the
      disease. The course of their trajectory through the progression of the disease
      remains uncertain; while they are already present during childhood or adolescence
      in some subjects who will later declare schizophrenia, they seem to worsen during
      the period of early prodroms, that is years before psychotic symptoms emerge.
      Whether they aggravate again during the first episode process is still a matter
      of debate. While longer DUP is associated with a poor outcome, this does not seem
      to hold true for cognitive impairments. Cannabis or tobacco use are neither
      associated with worse cognitive abilities in first-episode patients; a reverse
      relationship even sometimes exists. Cognitive impairment appears as largely
      independent from other clinical dimensions, acknowledging its own physiopathology
      and requiring specific evaluation and treatment. Several cognitive batteries can
      be used in clinical practice to explore cognitive abilities in first-episode
      patients; this is a necessary step before treating. While current pharmacological
      treatments display little or no efficacy for treating cognitive impairments, new
      medications offer some hope for the future. Still, efforts especially concern
      cognitive remediation for the moment. Several programs can be used in patients
      following their first episode, and some studies suggest that deficits in
      cognition are more amenable to remediation during earlier phases of the illness
      especially when cognitive remediation is associated with psychosocial
      rehabilitation, including school or work support. In the future, exploring and
      treating cognitive difficulties in first episode patients appear as a matter of
      collaborative work between psychiatrists and cognitive psychologists and between
      health and social services. 

PMID- 24084428
TI  - [Brain imaging of first-episode psychosis].
AB  - In the last decades, schizophrenia has intensively been studied using various
      brain imaging techniques. However, several potential confounding factors limited
      their interpretation power (e.g. chronicity, the impact of antipsychotic
      medication). By considering psychosis as a continuum of changes starting from
      mild cognitive impairments to serious psychotic symptoms, it became possible to
      provide deeper insight in the neurobiological mechanisms underlying the onset of
      psychosis by focusing on at-risk individuals and first-episodes. Recent brain
      imaging meta-analyses of the first episode psychosis (FEP), noteworthy reported
      conjoint bilateral structural and functional differences at the level of the
      insula, the superior temporal gyrus and the medial frontal gyrus, encompassing
      the anterior cingulate cortex. In the present review, we thus provide an update
      of brain imaging studies of FEP with a particular emphasis on more recent
      anatomical, functional and molecular explorations. Specifically, we provide 1) a
      review of the common features observed in individuals with high risk for
      psychosis and changes characterizing the transition to psychosis, 2) a
      description of the environmental and drug factors influencing these
      abnormalities, 3) how these findings in FEP may differ from those observed in
      chronic individuals with schizophrenia, and 4) a short overview of new
      classification algorithms able to use MRI findings as valuable biomarkers to
      guide early detection in the prodromal phase of psychosis. 

PMID- 24084429
TI  - [Subjective feeling of patient on his illness and his treatment].
AB  - Subjective feeling of schizophrenic patients has been underestimated in the study
      of this illness. Subjective experience associated with the onset of the disease
      is of interest in a clinical point of view but also in the study of the
      underlying mechanisms. The fields of cognitive psychology, but also
      neuroscientific inputs, provide new paradigms to understand schizophrenia. In a
      more global perspective, subjective experience has an important impact on quality
      of life and is highly related to symptomatology and treatments. Identification of
      these subjective dimensions is needed to develop more efficacious strategies. 

PMID- 24084430
TI  - Identification of transmembrane domain 3, 4 & 5 residues that contribute to the
      formation of the ligand-binding pocket of the urotensin-II receptor.
AB  - Urotensin-II (UII), a cyclic undecapeptide, selectively binds the urotensin-II
      receptor (UT receptor), a G protein-coupled receptor (GPCR) involved in
      cardiovascular effects and associated with numerous pathophysiological conditions
      including hypertension, atherosclerosis, heart failure, pulmonary hypertension
      and others. In order to identify specific residues in transmembrane domains (TM)
      three (TM3), four (TM4) and five (TM5) that are involved in the formation of the
      UT receptor binding pocket, we used the substituted-cysteine accessibility method
      (SCAM). Each residue in the F118((3.20)) to S146((3.48)) fragment of TM3, the
      L168((4.44)) to G194((4.70)) fragment of TM4 and the W203((5.30)) to V232((5.59))
      fragment of TM5, was mutated, individually, to a cysteine. The resulting mutants
      were then expressed in COS-7 cells and subsequently treated with the positively
      charged sulfhydryl-specific alkylating agent methanethiosulfonate-ethylammonium
      (MTSEA). MTSEA treatment resulted in a significant reduction in the binding of
      (125)I-UII to TM3 mutants L126C((3.28)), F127C((3.29)), F131C((3.33)) and
      M134C((3.36)) and TM4 mutants M184C((4.60)) and I188C((4.64)). No loss of binding
      was detected following treatment by MTSEA for all TM5 mutants tested. In absence
      of a crystal structure of UT receptor, these results identify key determinants in
      TM3, TM4 and TM5 that participate in the formation of the UT receptor binding
      pocket and has led us to propose a homology model of the UT receptor. 

PMID- 24084431
TI  - GABAB receptor trafficking and interacting proteins: targets for the development
      of highly specific therapeutic strategies to treat neurological disorders?
AB  - GABAB receptors mediate slow inhibitory neurotransmission throughout the central
      nervous system thereby controlling the excitability of neurons. They have been
      implicated in numerous neurological disorders making them an attractive drug
      target. However, due to considerable side effects, the agonist baclofen is so far
      the only drug on the market targeting GABAB receptors, primarily for the
      treatment of spasticity. Because GABAB receptors are involved in a variety of
      brain functions it is rather unlikely to avoid unwanted effects with systemically
      administered drugs directly addressing ligand binding sites of the receptor. To
      minimize side effects, it would be desirable to target only those receptors
      involved in a given pathological state. This commentary discusses the idea that
      restoring impaired GABAB receptor function in diseased neurons by interfering
      with receptor-protein interactions may be an approach to specifically target only
      those receptors involved in the pathological state. Two recently discovered
      mechanisms that down-regulate the level of functional GABAB receptors most likely
      contribute to cerebral ischemia and neuropathic pain, respectively. In both
      mechanisms, small interfering peptides disrupting protein-protein interactions
      may offer a highly specific means to restore normal receptor function selectively
      at the site of malfunction. If restored functional GABAB receptor expression in
      these diseases has beneficial effects, this may serve as a starting point for the
      development of a highly specific therapeutic interventions. Such an approach is
      expected to minimize side effects because it promises to leave those GABAB
      receptors unaffected which are not involved in the dysfunction. 

PMID- 24084432
TI  - Intrinsic contracture of the hand: diagnosis and management.
AB  - Intrinsic contracture of the hand may result from trauma, spasticity, ischemia,
      rheumatologic disorders, or iatrogenic causes. In severe cases, the hand assumes
      a posture with hyperflexed metacarpophalangeal joints and hyperextended proximal
      interphalangeal joints as the contracted interossei and lumbrical muscles deform
      the natural cascade of the fingers. Considerable disability may result because
      weakness in grip strength, difficulty with grasping larger objects, and troubles
      with maintenance of hygiene commonly encumber patients. Generally, the diagnosis
      is made via history and physical examination, but adjunctive imaging,
      rheumatologic testing, and electromyography may aid in determining the underlying
      cause or assessing the severity. Nonsurgical management may be appropriate in
      mild cases and consists of occupational therapy, orthoses, and botulinum toxin
      injections. The options for surgical management are diverse and dictated by the
      cause and severity of contracture. 

PMID- 24084433
TI  - Objective Structured Clinical Examinations: a guide to development and
      implementation in orthopaedic residency.
AB  - Objective Structured Clinical Examinations (OSCEs) have been used extensively in
      medical schools and residency programs to evaluate various skills, including the
      six core competencies outlined by the Accreditation Council for Graduate Medical
      Education (ACGME). Orthopaedic surgery residency programs will be required by the
      ACGME to assess residents on core competencies in the Milestone Project. Thus, it
      is important that evaluations be made in a consistent, objective manner.
      Orthopaedic residency programs can also use simulation models in the examination
      to accurately and objectively assess residents' skills as they progress through
      training. The use of these models will become essential as resident work hours
      are decreased and opportunities to observe skills become more limited. In
      addition to providing a method to assess competency, OSCEs are a valuable tool
      for residents to develop and practice important clinical skills. Here, we
      describe a method for developing a successful OSCE for use in orthopaedic
      surgical resident training. 

PMID- 24084434
TI  - Femoral bone loss in revision total hip arthroplasty: evaluation and management.
AB  - Primary total hip arthroplasty (THA) is one of the most effective procedures for
      managing end-stage hip arthritis. The burden of revision THA procedures is
      expected to increase along with the rise in number of primary THAs. The major
      indications for revision THA include instability, aseptic loosening, infection,
      osteolysis, wear-related complications, periprosthetic fracture, component
      malposition, and catastrophic implant fracture. Each of these conditions may be
      associated with mild or advanced bone loss. Careful patient evaluation and bone
      loss classification guide preoperative planning and overall patient care.
      Historically, uncemented fixation has provided the best results, but cemented
      fixation is required in some cases. 

PMID- 24084435
TI  - Fatty infiltration and rotator cuff atrophy.
AB  - Moderate to severe fatty infiltration and rotator cuff atrophy are commonly
      associated with poor clinical outcomes and failed rotator cuff repair. Numerous
      animal and human studies have attempted to elucidate the etiology of fatty
      infiltration and rotator cuff atrophy. Mechanical detachment of the tendon in
      rotator cuff tears is primarily responsible. Suprascapular nerve injury may also
      play a role. CT, MRI, and ultrasonography are used to evaluate severity. The
      Goutallier staging system is most commonly used to evaluate fatty infiltration,
      and rotator cuff atrophy is measured using multiple techniques. The presence and
      severity of fatty infiltration have been associated with increasing age, tear
      size, degree of tendon retraction, number of tendons involved (ie, massive
      tears), suprascapular neuropathy, and traumatic tears. Fatty infiltration is
      irreversible and progressive if left untreated. Slight reversal of muscle atrophy
      has been noted after repair in some studies. Novel therapies are currently being
      evaluated that may eventually allow clinicians to alter the natural history and
      improve patient outcomes. 

PMID- 24084436
TI  - Minor traumatic brain injury: a primer for the orthopaedic surgeon.
AB  - Minor traumatic brain injury (mTBI) is a major public health problem. The Centers
      for Disease Control and Prevention and the National Center for Injury Prevention
      and Control label it a "silent epidemic." Subtle signs and symptoms of mTBI,
      including headache, fatigue, and memory loss, are often seen in conjunction with
      musculoskeletal trauma. Although sometimes evident immediately, mTBI may not
      manifest until patients return to work and their personal lives. In the patient
      with acute concurrent mTBI, skeletal management must be based on either a period
      of observation to rule out evolving neurologic symptoms or, when warranted, the
      recommendations of a neurosurgeon. Such input is particularly important when mTBI
      is associated with a prolonged loss of consciousness or posttraumatic amnesia. In
      the outpatient setting, when concern for mTBI exists weeks after an injury,
      familiarity with and referral to locally available mTBI specialists and programs
      can facilitate proper care. Armed with this knowledge, the orthopaedic surgeon
      has an opportunity to positively influence outcomes and help provide crucial care
      that extends beyond the management of musculoskeletal injuries. 

PMID- 24084437
TI  - Septic arthritis of the neonatal hip: acute management and late reconstruction.
AB  - Septic arthritis of the hip in neonates is rare but can have devastating
      consequences. Presenting signs and symptoms may differ from those encountered in
      older children, which may result in diagnostic challenge or delay. Many risk
      factors predispose neonates to septic arthritis, including the presence of
      transphyseal vessels and invasive procedures. Bacterial infection of the joint
      occurs via hematogenous invasion, extension from an adjacent site, or direct
      inoculation. A strong correlation exists between younger age at presentation and
      severity of residual hip deformity. Diagnosis is based on clinical examination,
      laboratory markers, and ultrasound evaluation. Early management includes
      parenteral antibiotics and surgical drainage. Late-stage management options
      include femoral and pelvic osteotomies, trochanteric arthroplasty, arthrodesis,
      pelvic support procedures, and nonsurgical measures. Early diagnosis and
      management continues to be the most important prognostic factor for a favorable
      outcome in the neonate with septic arthritis. 

PMID- 24084438
TI  - Update on biologics in the treatment of rotator cuff disease.

PMID- 24084439
TI  - Serum biomarkers as predictors of stage of work-related musculoskeletal
      disorders.

PMID- 24084440
TI  - Microfluidic on-chip capture-cycloaddition reaction to reversibly immobilize
      small molecules or multi-component structures for biosensor applications.
AB  - Methods for rapid surface immobilization of bioactive small molecules with
      control over orientation and immobilization density are highly desirable for
      biosensor and microarray applications. In this Study, we use a highly efficient
      covalent bioorthogonal [4+2] cycloaddition reaction between trans-cyclooctene
      (TCO) and 1,2,4,5-tetrazine (Tz) to enable the microfluidic immobilization of
      TCO/Tz-derivatized molecules. We monitor the process in real-time under
      continuous flow conditions using surface plasmon resonance (SPR). To enable
      reversible immobilization and extend the experimental range of the sensor
      surface, we combine a non-covalent antigen-antibody capture component with the
      cycloaddition reaction. By alternately presenting TCO or Tz moieties to the
      sensor surface, multiple capture-cycloaddition processes are now possible on one
      sensor surface for on-chip assembly and interaction studies of a variety of multi
      component structures. We illustrate this method with two different immobilization
      experiments on a biosensor chip; a small molecule, AP1497 that binds FK506
      binding protein 12 (FKBP12); and the same small molecule as part of an
      immobilized and in situ-functionalized nanoparticle. 

PMID- 24084441
TI  - A phase II study with cetuximab and radiation therapy for patients with
      surgically resectable esophageal and GE junction carcinomas: Hoosier Oncology
      Group G05-92.
AB  - INTRODUCTION: On the basis of the promising activity of cetuximab and radiation
      therapy for head and neck cancers, we evaluated the efficacy of this regimen
      followed by surgery in patients with resectable esophageal cancer. This was a
      phase II, open-label, single-arm, multicenter study of patients with potentially
      resectable esophageal cancer. METHODS: Patients received two weekly doses of
      cetuximab followed by weekly cetuximab combined with radiation therapy for 6
      weeks. After a 6- to 8-week rest, patients' primary tumor was resected. The main
      objective was to evaluate pathologic complete response (pCR) rate in the primary
      tumor after cetuximab and radiation therapy. RESULTS: Thirty-nine patients
      completed the study. Most patients were men (93%), median age was 64 years,
      performance status was 0 to 1 (95%), patients had a histology of adenocarcinoma
      (78%), and tumors were located in the esophagus (63%). Grade 3 toxicities in more
      than 5% of patients included dysphagia (17%), anorexia and dehydration (7%), and
      dyspnea, fatigue, hypernatremia (5%). Grade 5 aspiration occurred in 2% (1
      patient). Four patients died, two from disease progression, one from aspiration
      pneumonia postsurgery, and one from septic shock. Thirty-one patients (76%)
      underwent esophagectomy. The pCR rate was 36.6% by intention-to-treat and 48% for
      patients who underwent esophagectomy. The pCR by histology was 6 of 9 (67%) for
      squamous cell carcinomas and 9 of 32 (28%) for adenocarcinoma. Earlier-stage
      disease was associated with increased pCR (IIA 70%, IIB 29%, III 28%).
      CONCLUSIONS: Cetuximab and radiation therapy results in a pCR rate that seems at
      least comparable with that of chemotherapy and radiation therapy. This regimen
      may be better tolerated than preoperative chemotherapy and radiation therapy in
      patients with resectable esophageal cancers.

PMID- 24084443
TI  - Post-surgical thyroid ablation in intermediate risk-differentiated thyroid cancer
      patients.

PMID- 24084442
TI  - Differential expression of extracellular matrix constituents and cell adhesion
      molecules between malignant pleural mesothelioma and mesothelial hyperplasia.
AB  - INTRODUCTION: Malignant pleural mesothelioma (MPM) is a highly aggressive
      neoplasm associated with asbestos exposure. Currently, the molecular mechanisms
      that induce MPM development are still unknown. The purpose of this study was to
      identify new molecular biomarkers for mesothelial carcinogenesis. METHODS: We
      analyzed a panel of 84 genes involved in extracellular matrix remodeling and cell
      adhesion by polymerase chain reaction (PCR) array in 15 samples of epithelioid
      mesothelioma and 10 samples of reactive mesothelial hyperplasia (MH; 3 of 25
      samples were inadequate for mRNA analysis). To validate the differentially
      expressed genes identified by PCR array, we analyzed 27 more samples by
      immunohistochemistry, in addition to the 25 samples already studied. RESULTS:
      Twenty-five genes were differentially expressed in MPM and MH by PCR array. Of
      these we studied matrix metalloproteinase 7 (MMP7), MMP14, CD44, and integrin,
      alpha3 expression by immunohistochemistry in 26 epithelioid MPM and 26 MH samples
      from the entire series of 52 cases. We observed higher MMP14 and integrin, alpha3
      expression in MPM samples compared with MH samples (p = 0.000002 and p =
      0.000002, respectively). Conversely, CD44 expression was low in most (57.7%)
      mesothelioma samples but only in 11.5% of the MH samples (p = 0.0013). As regards
      MMP7, we did not observe differential expression between MH and MPM samples.
      CONCLUSIONS: We have extensively studied genes involved in cell adhesion and
      extracellular matrix remodeling in MPM and MH samples, gaining new insight into
      the pathophysiology of mesothelioma. Moreover, our data suggest that these
      factors could be potential biomarkers for MPM.

PMID- 24084444
TI  - Reply to letter: Post-surgical thyroid ablation in intermediate risk
      differentiated thyroid cancer patients.

PMID- 24084445
TI  - Molecular mechanism of inhibitory effects of CD59 gene on atherosclerosis in ApoE
      (-/-) mice.
AB  - BACKGROUND: How to find an effective gene locus resistant to atherosclerosis has
      become a hotspot of today's medicine. Membrane attack complex (MAC) has proved to
      be related with the occurrence and development of atherosclerosis. Complement
      regulatory protein CD59 is a key regulator of complement MAC assembly. So this
      study aimed at discussing the effects of CD59 gene on occurrence and development
      of atherosclerosis and relative mechanism. METHODS: Apolipoprotein E knockout
      (ApoE (-/-)) mice were randomly divided into four groups: control group, empty
      plasmid-treated group, 0.5 ml CD59-treated group and 1.0 ml CD59-treated group.
      At the end of the 12th week, CD59 mRNA levels in whole blood were determined by
      RT-PCR and CD59 protein expressions were detected by western blot. The
      biochemical indexes in blood serum were detected. The paraffin sections of aortic
      root of mice were made and the degrees of atherosclerotic plaques formation were
      observed by hematoxylin/eosin (HE) staining. The expressions of cell apoptosis
      related proteins (Bcl-2 and Fas) and plaque stability related protein (MMP-2)
      were detected by immunohistochemistry. Then the cell apoptosis levels were
      detected by TUNEL, the expression of Cyclin D1 and the mRNA level of cyclin
      dependent protein kinase 4 (CDK4) were detected by immunofluorescence and in situ
      hybridization, respectively. RESULTS: Atherosclerotic mouse model was
      successfully established. CD59 gene was overexpressed in blood cells and tissue
      cells after liposome transfection. CD59 could reduce blood lipid levels, promote
      the expression of anti-apoptotic Bcl-2 protein and inhibit pro-apoptotic Fas
      proteins, so finally lead to degradation of apoptosis levels of endothelial
      cells. In addition, Cyclin D1 protein and CDK4 mRNA levels were restrained by
      CD59 so as to inhibit the proliferation of smooth muscle cells. CD59 could
      inhibit the formation of atherosclerotic vulnerable plaque by suppressing the MMP
      2 expression, which was further confirmed by HE staining. The anti
      atherosclerotic effects were enhanced with the increase of CD59 gene dose.
      CONCLUSIONS: CD59 could lower blood lipid levels, positively regulate cell cycle,
      maintain the stability of cell proliferation and apoptosis of aorta cells, slow
      down the development of atherosclerotic vulnerable plaque, and finally inhibit
      the progress of atherosclerosis. So CD59 gene might be a new genetic locus for
      the therapy of atherosclerosis.

PMID- 24084446
TI  - Cytokine Induced Killer (CIK) cells for the treatment of haematological
      neoplasms.
AB  - Cytokine Induced Killer (CIK) cells are in vitro activated human CD8 T cells
      which have maintained several characteristics of T-EMRA cells and additionally
      acquired non specific anti tumoral cytotoxicity and CD56 overexpression, thus
      representing a cell population with double T and NK phenotype. Due to their in
      vivo intratumoral homing and lack of Graft versus Host (GVH) reactivity, CIK
      cells have been extensively used in cancer patients either in autologous or
      allogeneic contexts. Here we summarise CIK main biological features as well as
      their most prominent clinical results. 

PMID- 24084447
TI  - Electron-hole pair condensation and Coulomb drag effect in a graphene double
      layer.
AB  - The spatially separated electron-hole pair condensation and Coulomb drag effect
      are studied theoretically in a graphene double layer. The main research results
      are presented as follows: we derive a critical average spacing of particles for
      the pair condensation to start at zero temperature, which is determined by the
      permittivity and thickness of the dielectric film between the two sheets of the
      graphene double layer; we obtain the phase diagram of condensates by introducing
      the ground-state fidelity, which accurately differentiates the Bose-Einstein
      condensate, Bardeen-Cooper-Schrieffer state, and their crossover; we confirm that
      the superfluid portion decreases the drag conductivity for a given gate voltage
      at finite temperatures; we find there exists a minimum drag conductivity by
      increasing the gate voltage, which results from the combined effect of the
      longitudinal conductivity in each graphene layer and superfluid density. The last
      result is especially useful for detecting the pair condensation experimentally.

PMID- 24084448
TI  - Cross-cultural adaptation of the Health Education Impact Questionnaire:
      experimental study showed expert committee, not back-translation, added value.
AB  - OBJECTIVES: To assess the contribution of back-translation and expert committee
      to the content and psychometric properties of a translated multidimensional
      questionnaire. STUDY DESIGN AND SETTING: Recommendations for questionnaire
      translation include back-translation and expert committee, but their contribution
      to measurement properties is unknown. Four English to French translations of the
      Health Education Impact Questionnaire were generated with and without committee
      or back-translation. Face validity, acceptability, and structural properties were
      compared after random assignment to people with rheumatoid arthritis (N = 1,168),
      chronic renal failure (N = 2,368), and diabetes (N = 538). For face validity, 15
      bilingual people compared translations quality with the original. Psychometric
      properties were examined using confirmatory factor analysis (metric and scalar
      invariance) and item response theory. RESULTS: Qualitatively, there were five
      types of translation errors: style, intensity, frequency/time frame, breadth, and
      meaning. Bilingual assessors ranked best the translations with committee (P =
      0.0026). All translations had good structural properties (root mean square error
      of approximation <0.05; comparative fit index [CFI], >=0.899; and Tucker-Lewis
      index, >=0.889). Full measurement invariance was observed between translations
      (DeltaCFI <= 0.01) with metric invariance between translations and original
      (lowest DeltaCFI = 0.022 between fully constrained models and models with free
      intercepts). Item characteristic curve analyses revealed no significant
      differences. CONCLUSION: This is the first experimental evidence that back
      translation has moderate impact, whereas expert committee helps to ensure
      accurate content.

PMID- 24084449
TI  - Development of solid dispersions of artemisinin for transdermal delivery.
AB  - Solid dispersions of the poorly soluble drug artemisinin were developed using
      polymer blends of polyvinylpyrrolidone (PVP) and polyethylene glycol (PEG) with
      the aim of enhancing solubility and in vitro permeation of artemisinin through
      skin. Formulations were characterised using a combination of molecular dynamics
      (MD) simulations, differential scanning calorimetry (DSC), X-ray diffraction
      (XRD) and Fourier transform infrared spectroscopy (FT-IR). Solubility of
      artemisinin was determined in two solvents: de-ionised water and phosphate
      buffered saline (PBS; pH 7.4), while in vitro drug permeation studies were
      carried out using rabbit skin as a model membrane. MD simulations revealed
      miscibility between the drug and polymers. DSC confirmed the molecular dispersion
      of the drug in the polymer blend. Decrease in crystallinity of artemisinin with
      respect to polymer content and the absence of specific drug-polymer interactions
      were confirmed using XRD and FT-IR, respectively. The solubility of artemisinin
      was dramatically enhanced for the solid dispersions, as was the permeation of
      artemisinin from saturated solid-dispersion vehicles relative to that from
      saturated solutions of the pure drug. The study suggests that high energy solid
      forms of artemisinin could possibly enable transdermal delivery of artemisinin. 

PMID- 24084451
TI  - Tumor cell heterogeneity.
AB  - The paper deals with the analysis of literary data on the tumor cell
      heterogeneity. Phenotypic, genetic and epigenetic mechanisms of heterogeneity are
      considered. The heterogeneity of metastasis is considered too. The importance for
      the biology of populations of tumor cells and the sensitivity of tumors to
      therapeutic treatment are discussed. 

PMID- 24084450
TI  - Rapid and soft formulation of folate-functionalized nanoparticles for the
      targeted delivery of tripentone in ovarian carcinoma.
AB  - We report the development of folate-functionalized nanoparticles able to target
      folate receptors, and to deliver a poorly water soluble cytotoxic agent, a
      tripentone, in ovarian carcinoma. The stability under incubation of lipid
      nanoparticles formulated by a low-energy phase inversion temperature method was
      investigated. Thanks to the presence of Labrasol((r)), a macrogolglyceride into
      the composition of the nanocarriers, the conjugation of different quantities of a
      folate derivate (folic acid-polyethylene glycol2000
      distearylphosphatidylethanolamine) to nanoparticles was possible by a rapid,
      soft, very simple post-insertion process. As determined by dynamic light
      scattering, nanoparticles present a monodisperse diameter of about 100 nm, a
      spherical shape as attested by transmission electron micrographs, a weakly
      negative surface zeta potential, and are able to encapsulate the tripentone
      MR22388. The presence of folate receptors on SKOV3 human ovarian cancer cells was
      identified by fluorescent immunocytochemistry. Cellular uptake studies assessed
      by flow cytometry indicated that these nanoparticles reached the SKOV3 cells
      rapidly, and were internalized by a folate-receptor mediated endocytosis pathway.
      Moreover, nanoparticles allowed the rapid delivery of the antitumor agent
      tripentone into cells as shown in vitro by real-time cellular activity assay.
      Such folate-lipid nanoparticles are a potential carrier for targeted delivery of
      poorly water soluble compounds into ovarian carcinoma.

PMID- 24084452
TI  - Chronic periodontitis and the risk of head and neck squamous cell carcinoma:
      facts and figures.
AB  - Substantial evidence supports an association between periodontal disease and
      several systemic diseases including cardiovascular diseases, diabetes mellitus,
      respiratory diseases, adverse pregnancy outcomes, osteoporosis etc. Periodontal
      disease, a chronic inflammatory condition, is highly prevalent in adult
      populations around the world, and may be preventable. Estimates of prevalence
      vary between races and geographic regions, with a marked increase in the
      occurrence of periodontal disease with advancing age. Worldwide estimates for the
      prevalence of severe periodontal disease generally range from 10 to 15%. The
      relationship between periodontal disease and cancer has been examined for a
      number of specific cancer sites. The grim statistics of head and neck cancer
      incidence and survival have remained essentially unchanged over the past 3
      decades despite the prevention efforts against known risk factors of head and
      neck cancer, and advances in the diagnosis and treatment, arguing forcibly for
      new insights regarding the etiology as well as the strategies for prevention.
      Recent reports have linked periodontal disease with increased risk of squamous
      cell carcinoma of head and neck. This review provides current literature for a
      role of periodontal disease in carcinogenesis of head and neck region and
      discusses possible biological mechanisms involved. 

PMID- 24084453
TI  - Effects of alvocidib and carboplatin on ovarian cancer cells in vitro.
AB  - AIM: Failure of platinum chemotherapy is an unresolved issue in ovarian cancer.
      Targeted therapy has been added to the treatment options in solid cancers.
      Alvocidib is a cyclin dependent kinase inhibitor. MATERIALS AND METHODS: This
      study evaluated the effects of alvocidib together with carboplatin on ovarian
      cancer cells (BG-1 and Skov-3) in vitro applying proliferation assays, cell cycle
      distribution analyses, apoptosis induction assays, and drug accumulation assay.
      RESULTS: Proliferation of both cell lines was inhibited by carboplatin and
      alvocidib. The interaction index revealed drug synergism at distinct drug
      concentrations. Cell cycle distribution was altered. Alvocidib induced apoptosis
      in Skov-3 cells, and necrosis in BG-1 cells. Rhodamine accumulation was increased
      by alvocidib or both compounds together. CONCLUSION: These data provide evidence
      for antiproliferative effects of alvocidib on human ovarian cancer cells in vitro
      associated with changes in cell cycle distribution, the induction of apoptosis,
      and modulation of intracellular drug accumulation. Alvocidib and carboplatin
      showed some cooperative activity.

PMID- 24084454
TI  - Expression of biomarkers related to cell adhesion, metastasis and invasion of
      breast cancer cell lines of different molecular subtype.
AB  - AIM: The aim of our study was to determine the complex of molecular genetic
      markers which are associated with cancer aggressiveness, invasion and metastasis
      among different molecular subtypes of breast cancer cell lines. MATERIALS AND
      METHODS: The cell lines used in the analysis include T47D, MCF-7, MDA-MB-231, MDA
      MB-468, MCF-10A and 184A1. Expression of estrogen receptor, progesterone
      receptor, Her-2/neu and Ki-67 was studied by immunocytochemical method. CD24,
      CD44 and E-cadherin expression was studied by flow cytometry. RESULTS: We have
      identified biomarkers which characterize metastatic potential of human breast
      cancer cells of certain molecular subtypes. It has been demonstrated that low
      colony forming activity of human breast cancer cells of luminal subtype is
      accompanied by increased adhesive properties of these cells due to high level of
      E-cadherin expression, low level of CD44 expression and absence of CD24
      expression. High tumorigenicity of cells of basal subtype is connected to
      weakening of adhesive contacts that is caused by abnormalities of E-cadherin
      expression, significant increase of CD44 expression and presence of low level of
      CD24 expression. CONCLUSION: Our data indicated that changes of correlation
      between expression of cellular adhesion molecules inside conventional
      immunohistochemical subtypes reflect significantly wider biological properties of
      luminal and basal subtypes of human breast cancer.

PMID- 24084455
TI  - Inhibition of growth and expression of inflammation mediators in human leukemic
      cell line U-937 by a nutrient mixture.
AB  - AIM: A nutrient mixture (NM) containing ascorbic acid, lysine, proline and green
      tea extract has exhibited anticancer activity in vitro and in vivo in a number of
      cancer cell lines. We investigated the effect of NM on human leukemic myeloid U
      937 cells in vitro by measuring: cell proliferation, MMP expression, invasion,
      apoptosis, and COX-2 and COX-1 protein expression. METHODS: Human leukemic cell
      line U-937 (ATCC) was cultured in RPMI medium supplemented with fetal bovine
      serum and antibiotics. After 24 h, the cells were treated with NM at 0, 50, 100,
      250, 500 and 1000 Ojg/ml, in triplicate at each dose. Phorbol 12-myristate 13
      acetate (PMA), 100 ng/ml was added to cells to induce MMP-9 secretion. Cell
      proliferation was evaluated by MTT assay, MMP expression by gelatinase
      zymography, invasion through Matrigel, apoptosis by using live green caspase
      detection kit (Molecular Probe), and COX-2 and COX-1 expression by Western blot.
      RESULTS: NM had no effect on U-937 cell growth at a concentration of 250 Ojg/ml
      and exhibited an antiproliferative effect at 500 Ojg/ml concentration. Zymography
      did not demonstrate MMP-2 or MMP-9 secretion in normal cells; however, PMA
      strongly induced MMP-9, which was inhibited by NM in a dose-dependent manner.
      Cell penetration through Matrigel was significantly reduced (by 95%) at 250
      Ojg/ml NM and completely blocked at 500 Ojg/ml NM. NM induced slight apoptosis at
      100 Ojg/ml and moderate at 500 and 1000 Ojg/ml concentration. NM inhibited COX-2
      expression in a dose-dependent fashion and had no effect on COX-1 expression.
      CONCLUSIONS: Our results suggest that NM has potent inhibitory effects on U-937
      cell growth and expression of inflammatory mediators, significant parameters in
      AML progression.

PMID- 24084456
TI  - TNFalpha receptor1 drives hypoxia-promoted invasiveness of human melanoma cells.
AB  - AIM: Oxygen deprivation leading to hypoxia represents a common feature of
      advanced solid tumors, able to control several aspects of tumor progression.
      Indeed, ability to respond to changes in oxygen partial pressure represents a
      hallmark of malignant cells. Aim of this study is to disclose new pathway of
      hypoxia-induced tumor cell invasion. MATERIALS AND METHODS: Hs294T human melanoma
      cells were grown in a gas mixture containing 0.3% O2 and used to evaluate
      invasion on Matrigel-coated polycarbonate filters mounted in Boyden's chambers,
      MMP release and expression of inflammatory receptors and their ligands. RESULTS:
      We demonstrate that hypoxia promotes the expression of TNFalpha receptor 1
      (TNFalphaR1) able to drive a higher ability to penetrate Matrigel-coated filters
      of Hs294T human melanoma cells, an effect does not mediated by hypoxia-inducible
      factor (HIF)-1alpha. CONCLUSION: Expression of inflammatory cytokine receptors in
      hypoxic human melanoma cells might provide a new target for improving strategies
      against local and distant tumor cell diffusion.

PMID- 24084457
TI  - Alteration in lipid composition of plasma membranes of sensitive and resistant
      Guerin carcinoma cells due to the action of free and liposomal form of cisplatin.
AB  - AIM: To study in vivo changes of lipid composition of plasma membranes of
      sensitive and resistant to cisplatin Guerin carcinoma cells under influence of
      free and liposomal cisplatin forms. MATERIALS AND METHODS: The isolation of
      plasma membranes from parental (sensitive) and resistant to cisplatin Guerin
      carcinoma cells was by differential ultracentrifugation in sucrose density
      gradient. Lipids were detected by method of thin-layer chromatography. RESULTS:
      It was determined that more effective action of cisplatin liposomal form on
      resistant cells is associated with essential abnormalities of conformation of
      plasma membrane due to change of lipid components and architectonics of rafts. It
      results in the increase of membrane fluidity. CONCLUSION: Reconstructions in
      lipid composition of plasma membranes of cisplatin-resistant Guerin carcinoma
      cells provide more intensive delivery of drug into the cells, increase of its
      concentration and more effective interaction with cellular structural elements.

PMID- 24084458
TI  - Glycopeptide vaccine on DNA-histone carrier and its impact on Z-potential of
      effector cells during experimental treatment of lymphoblastic leukemia.
AB  - AIM: To increase the effectiveness of anticancer vaccine delivery and activity
      via its immobilization on reconstructed chromatin (RC). MATERIALS AND METHODS:
      The hybrid mice of CDF-1 line with transplanted P-388 leukemia were used.
      Reconstructed chromatin was obtained from the thymus of inbred rats. Glycopeptide
      cancer vaccine prepared from P-388 leukemia cells, was immobilized of RC. zeta
      potential of thymocytes from tumor-bearing mice was calculated from Smoluchowski
      equation. RESULTS: The data have demonstrated the principal possibility of using
      the fragments of reconstructed chromatin of heterologous origin as a carrier of
      glycopeptide cancer vaccine prepared from the cells of P-388 leukemia. Preventive
      immunization with the correspondingly immobilized vaccine normalized zeta
      potential of thymocytes in animals with transplanted P-388 leukemia. CONCLUSIONS:
      The use of immobilization of glycopeptide cancer vaccine on reconstructed
      chromatin improves anticancer activity of the vaccination.

PMID- 24084459
TI  - Molecular characterization of Ph-negative myeloproliferative neoplasms in
      Ukraine.
AB  - AIM: The aim of this study was to examine the JAK2 V617F, the G1691A allele of
      factor V, and the G20210A prothrombin gene mutation status, and their predictive
      value for thrombosis in patients with Ph-negative myeloproliferative neoplasms
      (MPN) in Ukraine, with special emphasize to patient exposed to ionizing radiation
      due to the Chernobyl accident. MATERIALS AND METHODS: There were 198 patients
      with Ph-negative MPN included in the study. Of these, 45 patients had experienced
      radiation exposure due to the Chernobyl accident. The JAK2 V617F mutation, the
      G1691A of factor V and the G20210A of prothrombin were detected by allele
      specific polymerase chain reaction. RESULTS: The polycythemia vera and essential
      thrombocythemia patients in unexposed group and Chernobyl patients were
      comparable in terms of the JAK2 V617F mutation prevalence with the frequency of
      anomaly corresponding well to the published data on unselected cases of these
      types of Ph-negative MPN. The JAK2 V617F mutation was less common on the border
      of statistical significance (p = 0.08) in Chernobyl primary myelofibrosis (PMF)
      patients than in non-exposed patients. JAK2 V617F positive patients had higher
      level of leukocytes (p = 0.03), hemoglobin (p =0.04) and splenomegaly (p = 0.04)
      than those without mutation. The JAK2 V617F mutation was strong predictor for
      thrombosis in essential thrombocytemia patients (relative risk=3.1, 95% CI = 1.7
      16.4, p = 0.03). In PMF, the association with thrombosis was found for the G1691A
      allele of factor V (p = 0.03). The risk of thrombosis associated with the
      inherited thrombophilia in PMF patients was 7.0-fold (95% CI = 1.41-33.1, p =
      0.03) higher than in polycythemia vera patients. The inherited thrombophilia
      increased risk of thrombotic complication 5.4-fold (95% CI = 1.41-18.17, p =
      0.01) in overall cohort of Ph-negative myeloproliferative neoplasms patients.
      This trend continued in Chernobyl patients (p = 0.02), but not in unexposed
      cases. CONCLUSIONS: Our findings confirm previous results of other studies
      reporting that the JAK2 V617F mutation significantly and independently influences
      on a disease phenotype in Ph-negative MPN. The inherited thrombophilia is
      important risk factors of the thrombosis development in overall cohort primary
      myelofibrosis patients, and especially in disease developed following radiation
      exposure.

PMID- 24084460
TI  - Antibodies against benzo[a]pyrene in immunized mouse and in lung cancer patients.
AB  - AIM: To evaluate the production of antibodies against benzo[a]pyrene (BP) (Ab1)
      and corresponding antiidiotypic antibodies (Ab2) in mice after immunization with
      BP-protein conjugate and in lung cancer patients. MATERIALS AND METHODS: The Ab1
      and Ab2 levels were measured by non-competitive ELISA in blood serum of 10 mice
      immunized with BP-protein conjugate, and in blood serum of 288 healthy persons
      and 165 lung cancer patients. RESULTS: The Ab1 level of was 2-fold higher than
      Ab2 level in blood serum of BP-immunized mice. In lung cancer patients the Ab1
      level was almost 3 times higher and the Ab2 level was by 30% higher than these
      indexes in healthy individuals. The Ab1/Ab2 ratio was 2 in BP-immunized mice and
      healthy individuals and 1 in lung cancer patients. CONCLUSION: Our data have
      shown that the Ab1/Ab2 ratio in lung cancer patients differ from that in healthy
      individuals and is close to the Ab1/Ab2 ratio in BP-immunized mouse.

PMID- 24084461
TI  - Significance of adhesion molecules expression for estimation of serous ovarian
      cancer prognosis.
AB  - AIM: To study the adhesion molecules CD44 and E-cadherin expression in serous
      ovarian cancer (OC) and their relationship with clinicopathological peculiarities
      of tumor process and prognosis. MATERIALS AND METHODS: The study was performed on
      OC samples from 72 patients with serous OC of stages I-III. Expression of CD44
      and E-cadherin in tumor samples was evaluated with the use of immunohistochemical
      analysis. RESULTS: Immunohistochemical analysis has revealed that in 58.3% of OC
      patients CD44 expression was detected in more than 10% of cells with average
      level of 30.0V+/-5.6%. E-cadherin expression was present in 47.2% of tumors, and
      12.2V+/-3.6% cells were immunopositive. CD44 and E-cadherin expression depends on
      degree of cytomorphological malignancy and cell differentiation. A reverse
      correlation between CD44 and E-cadherin expression in primary serous OC (r=-0.38,
      p < 0.05) has been found. Increased CD44 expression (mean index) was not observed
      in peritoneal metastases compared to primary tumors, but analysis of individual
      indexes showed increase of CD44 expression in 46.6% OC patients with metastases.
      The dependence between overall survival of OC patients and the molecular
      phenotype of tumor cells, in particular, poor prognosis for OC patients with
      CD44(+)/E-cadherin(-) and CD44(+)/budding(+) tumor cells phenotype, has been
      revealed. CONCLUSION: The results of morphological and immunohistochemical
      analysis has shown the increase of adhesive features of serous ovarian cancer
      cells what may be significant for estimation of ovarian cancer aggressiveness and
      development of metastatic process.

PMID- 24084462
TI  - Overproduction of free radical species in embryonal cells exposed to low
      intensity radiofrequency radiation.
AB  - AIM: Long-term exposure of humans to low intensity radiofrequency electromagnetic
      radiation (RF-EMR) leads to a statistically significant increase in tumor
      incidence. Mechanisms of such the effects are unclear, but features of oxidative
      stress in living cells under RF-EMR exposure were previously reported. Our study
      aims to assess a production of initial free radical species, which lead to
      oxidative stress in the cell. MATERIALS AND METHODS: Embryos of Japanese quails
      were exposed in ovo to extremely low intensity RF-EMR of GSM 900 MHz (0.25
      uW/cm2) during 158-360 h discontinuously (48 c - ON, 12 c - OFF) before and in
      the initial stages of development. The levels of superoxide (O2.-), nitrogen
      oxide (NO.), thiobarbituric acid reactive substances (TBARS), 8-oxo-2'
      deoxyguanosine (8-oxo-dG) and antioxidant enzymes' activities were assessed in
      cells/tissues of 38-h, 5- and 10-day RF-EMR exposed and unexposed embryos.
      RESULTS: The exposure resulted in a significant persistent overproduction of
      superoxide and nitrogen oxide in embryo cells during all period of analyses. As a
      result, significantly increased levels of TBARS and 8-oxo-dG followed by
      significantly decreased levels of superoxide dismutase and catalase activities
      were developed in the exposed embryo cells. CONCLUSION: Exposure of developing
      quail embryos to extremely low intensity RF-EMR of GSM 900 MHz during at least
      one hundred and fifty-eight hours leads to a significant overproduction of free
      radicals/reactive oxygen species and oxidative damage of DNA in embryo cells.
      These oxidative changes may lead to pathologies up to oncogenic transformation of
      cells.

PMID- 24084463
TI  - Human DNA ligase i (ligi) gene and risk of cervical cancer in North Indian women.
AB  - AIM: DNA repair genetic polymorphisms may affect cancer susceptibility as genetic
      variations in DNA repair genes may influence DNA repair capacity. In the present
      study, the association of polymorphic forms of DNA repair gene, DNA ligase I
      (LIGI) was examined with the risk of cervical cancer in case of North Indian
      women. MATERIALS AND METHODS: Polymorphism was determined by polymerase chain
      reaction - restriction fragment length polymorphism (PCR-RFLP) method and risk of
      cervical cancer was evaluated by calculating odds ratios (ORs) and 95% confidence
      interval (CI) using a multivariate logistic regression analysis. RESULTS: No
      association was found between variant forms (AC, AA) of LIGI gene and risk of
      cervical cancer (OR - 0.8, 95% CI 0.46-1.53 and OR - 1.0, 95% CI 0.51-2.06,
      respectively). However, increased but statistically non-significant risk of
      adenocarcinoma was observed for cervical cancer patients having AC (OR - 4.6, 95%
      CI 0.62-33.82) and AA (OR - 5.0, 95% CI 0.63-39.58) genotypes. CONCLUSION: It can
      thus be concluded that there is no association between LIGI polymorphisms and
      cervical cancer risk. However, they may be playing an important role in
      modulating the risk of cervical adenocarcinoma in North Indian women. Further
      investigations in larger studies need to be carried out for more analysis.

PMID- 24084464
TI  - Evaluation of serum levels of multiple cytokines and adhesion molecules in
      patients with newly diagnosed acute lymphoblastic leukemia using biochip array
      technology.
AB  - AIM: Evaluation of serum levels of 17 cytokines and 5 adhesion molecules in
      patients with acute lymphoblastic leukemia (ALL) and in healthy subjects using
      biochip array technology. This approach allows multi-analytical determination
      from a single sample. METHODS: A total of 15 ALL patients and 15 healthy subjects
      (blood donors) were studied. Serum samples were analyzed by biochip based
      immunoassays on the Evidence Investigator analyzer. T-tests were used for
      statistical analysis. RESULTS: Comparing cytokine and adhesion molecule levels in
      ALL patients and in healthy subject, we found significant increase in serum VCAM
      1 (p < 0.000001), ICAM-1 (p < 0.0001), L-selectin (p < 0.0001), IL-8 (p < 0.001),
      MCP-1 (p < 0.01), and significant decrease (p < 0.01) in serum IL-3 and IL-4.
      CONCLUSION: Our results indicate that serum levels of specific cytokines and
      adhesion molecules (VCAM-1, ICAM-1, L-selectin, IL-8, IL-3, IL-4, MCP-1) are
      significantly altered in patients with newly diagnosed ALL, reflecting acti-vity
      of the disease. Further investigation is needed to establish if these alterations
      could be used as a prognostic indicator for ALL.

PMID- 24084465
TI  - The 11th International Congress on Targeted Anticancer Therapies Paris, 4-6 March
      2013 (TAT 2013).

PMID- 24084466
TI  - What you see is what you fear.
AB  - Visual imagery can powerfully shape perceptions of risks as is clearly
      demonstrated by research on the use of graphic warnings on cigarette packs.
      Government efforts to counteract public fears of vaccines could harness this
      phenomenon by using public information campaigns that present visually the
      effects of vaccine-preventable diseases. Visual representations can also be used
      to communicate the relative risks of vaccines, which are generally negligible,
      and of the diseases they prevent. Such initiatives have the policy advantage of
      minimizing the sense of government intrusion that measures such as vaccine
      mandates and social restrictions could engender and the legal advantage of
      avoiding claims of infringement on civil liberties. Government policy should take
      advantage of this important and accessible tool. 

PMID- 24084467
TI  - Cost-effectiveness of computer-tailored smoking cessation advice in primary care:
      a randomized trial (ESCAPE).
AB  - INTRODUCTION: Smoking remains a significant public health problem and is a
      leading cause of preventable morbidity and mortality around the world. By
      combining the behavioral intervention principles used in specialist services with
      the high reach rates of public health interventions, personal tailored self-help
      cessation intervention provides a potential economical method for improving reach
      and effectiveness. METHODS: Cost-effectiveness analysis is performed alongside a
      randomized controlled trial to compare the computer-tailored self-help
      intervention with a generic self-help intervention in smoking cessation. A Markov
      model was developed to extrapolate lifetime cost-effectiveness by combining trial
      data with estimates from the literature. FINDINGS: In the short term, smokers in
      the intervention group gained 0.0006 (95% CI = -0.0024 to 0.0036) quality
      adjusted life years (QALYs) more than those in the control group at an increased
      cost of about L9 per person (95% CI = L5-L12). This yielded an incremental cost
      effectiveness ratio (ICER) of L14,432/QALY. Precision of the ICER estimates was
      assessed by 5,000 bootstrapping replications. The probability that the
      intervention was cost effective was 54% (58%) at a cost-effectiveness threshold
      of L20,000(L30,000) per QALY. The Markov model showed that simulating lifetime
      outcomes improved the cost-effectiveness ratio (L9,700/QALY) in favor of the
      tailored intervention. The intervention would have a 55%-57% chance of being more
      cost effective than nontailored intervention at the willingness-to-pay threshold
      of L20,000-30,000/QALY. CONCLUSIONS: The computer-tailored intervention appears
      slightly more likely to be cost effective than the generic self-help intervention
      in smoking cessation, in both the short term and the long term, but caution is
      required given the considerable uncertainty surrounding the estimates.

PMID- 24084468
TI  - Prokaryotic cell division: flexible and diverse.
AB  - Gram-negative rod-shaped bacteria have different approaches to position the cell
      division initiating Z-ring at the correct moment in their cell division cycle.
      The subsequent maturation into a functional division machine occurs in vastly
      different species in two steps with appreciable time in between these. The
      function of this time delay is unclear, but may partly be explained by
      competition for Lipid-II between proteins involved in length growth that interact
      directly with the Z-ring early in the maturation phase and the proteins involved
      in septum synthesis. A second possible activity of the early Z-ring might be the
      monitoring of or the active involvement in DNA segregation through proteins such
      as ZapA and ZapB/MatP and their homologues. 

PMID- 24084469
TI  - Denoising and fast diffusion imaging with physically constrained sparse
      dictionary learning.
AB  - Diffusion-weighted imaging (DWI) allows imaging the geometry of water diffusion
      in biological tissues. However, DW images are noisy at high b-values and
      acquisitions are slow when using a large number of measurements, such as in
      Diffusion Spectrum Imaging (DSI). This work aims to denoise DWI and reduce the
      number of required measurements, while maintaining data quality. To capture the
      structure of DWI data, we use sparse dictionary learning constrained by the
      physical properties of the signal: symmetry and positivity. The method learns a
      dictionary of diffusion profiles on all the DW images at the same time and then
      scales to full brain data. Its performance is investigated with simulations and
      two real DSI datasets. We obtain better signal estimates from noisy measurements
      than by applying mirror symmetry through the q-space origin, Gaussian denoising
      or state-of-the-art non-local means denoising. Using a high-resolution dictionary
      learnt on another subject, we show that we can reduce the number of images
      acquired while still generating high resolution DSI data. Using dictionary
      learning, one can denoise DW images effectively and perform faster acquisitions.
      Higher b-value acquisitions and DSI techniques are possible with approximately 40
      measurements. This opens important perspectives for the connectomics community
      using DSI. 

PMID- 24084470
TI  - Neuroprotective effects of prior exposure to enriched environment on cerebral
      ischemia/reperfusion injury in rats: the possible molecular mechanism.
AB  - Increasing evidence shows that exposure to an enriched environment (EE) after
      cerebral ischemia/reperfusion injury is neuroprotective in animal models. Recent
      studies have demonstrated that animals housed in an enriched environment
      condition after an experimental stroke obtained a better functional outcome than
      those housed in a standard condition. However, little is known about the
      underlying mechanisms of neuroprotective effects of enriched environment exposure
      prior to injury. The current study examined the neuroprotective effects of prior
      enriched environment exposure after transient middle cerebral artery occlusion
      (MCAO) in rats. Male Sprague Dawley (SD) rats, weighing 55-65g at the beginning
      of the experiment, were randomly assigned to a pre-ischemic enriched environment
      (PIEE) or pre-ischemic standard condition (PISC) group for 1 month. They were
      weighed on days1, 7, 18, and 28, and their locomotor activity was tracked during
      the period between 9:00am and 3:00pm daily. After 1 month, ischemia was induced
      by occluding the middle cerebral artery for 90min, followed by reperfusion. After
      approximately 24h of the operation, functional outcomes were assessed using the
      beam-walking test and a neurological evaluation scale in all rats. We measured
      the expression of extracellular signal regulated protein kinases1/2 (ERK1/2) by
      western blotting and gene expression levels of neuronal nitric oxide synthase
      (nNOS) and inducible nitric oxide synthasen (iNOS) by Real-Time PCR in the
      cortical area affected by ischemia. Finally, we measured the level of
      malondialdehyde (MDA) content, which is a biomarker of oxidative stress. The
      results showed that rats in the PIEE group had lighter weight than those in the
      PISC group. The functional outcomes of rats in the PIEE group were better than
      those in the PISC group, and substances associated with inflammation, such as
      MDA, nNOS, iNOS, and phospho-ERK1/2, were lower in the PIEE group compared with
      the PISC group. These results indicate that enriched environment may provide
      neuroprotection via ischemic preconditioning and enhance resilience to cerebral
      ischemia. 

PMID- 24084471
TI  - Homeless mentally ill in Athens area: a cross-sectional study on unmet needs and
      help-seeking.
AB  - BACKGROUND: Homelessness, a worldwide psychosocial phenomenon, is now also
      prevalent in Greece, mainly in Athens area. METHODS: The possible psychiatric
      morbidity related to help-seeking and the underlying factors were explored in a
      sample of 254 homeless people from Greater Athens area, using the Mini
      International Neuropsychiatric Interview (M.I.N.I.). RESULTS: The sample was
      predominantly male (74%) with mean age of 51 years, being in their majority
      homeless for over 25 months, 34.3% of them living in rough sleeping places.
      Overall, 56.7% of the sample met the criteria for a current Diagnostic and
      Statistical Manual of Mental Disorders-Fourth Edition (DSM-IV) psychiatric
      disorder with 20.8% comorbidity. Only 36.2% of the identified psychiatric cases
      had any recent psychiatric care, while 44.4% were taking non-prescribed
      medication and 20.2% have been hospitalized in the last year. On the contrary,
      70% of alcohol- and drug-dependent persons have been treated in a psychiatric
      agency, while 60.0% of them participated in rehabilitation program the last year.
      Logistic regression analysis revealed that being older, more educated with longer
      duration of homelessness, recognizing the suffering from a psychiatric problem as
      well as being diagnosed as 'psychotic' increased the likelihood to seek help.
      CONCLUSIONS: The vast majority of the homeless mentally ill persons were lacking
      any current psychiatric care. The planning of a mental health-care delivery
      parallel to the existing social welfare system is needed to serve the unmet
      mental health needs of this population.

PMID- 24084472
TI  - Comment on "associations between PFOA, PFOS and changes in the expression of
      genes involved in cholesterol metabolism in humans" by Fletcher et al.,
      Environment International 57-58 (2013) 2-10.

PMID- 24084473
TI  - Metabolites from the endophytic [corrected] fungus Sporormiella minimoides
      isolated from Hintonia latiflora.
AB  - An extract of the solid cultures of Sporormiella minimoides (Sporormiaceae)
      isolated as an endophytic fungus from Hintonia latiflora (Rubiaceae), yielded
      three polyketides, 3,6-dimethoxy-8-methyl-1H,6H-benzo[de]isochromene-1,9-dione, 3
      hydroxy-1,6,10-trimethoxy-8-methyl-1H,3H-benzo[de]isochromen-9-one, and 5-hydroxy
      2,7-dimethoxy-8-methylnaphthoquinone, along with three known compounds,
      corymbiferone, ziganein, and brocaenol B. Their structures were characterized by
      spectrometric and spectroscopic methods. So as to be consistent the literature
      reports, 3,6-dimethoxy-8-methyl-1H,6H-benzo[de]isochromene-1,9-dione and 3
      hydroxy-1,6,10-trimethoxy-8-methyl-1H,3H-benzo[de]isochromen-9-one were given the
      trivial names of corymbiferone C and corymbiferan lactone E, respectively. All
      isolates were tested as potential human calmodulin (hCaM) inhibitors using the
      fluorescent biosensor hCaM V91C-mBBr, but only 5-hydroxy-2,7-dimethoxy-8
      methylnaphthoquinone quenched significantly the extrinsic fluorescence of this
      biosensor, with a dissociation constant (Kd) value of 1.55 MUM. Refined docking
      analysis predicted that 5-hydroxy-2,7-dimethoxy-8-methylnaphthoquinone could also
      be bound to hCaM at site I displaying hydrophobic interactions with Phe19 and 68,
      Met51, 71, and 72, and Ile52 and 63 residues.

PMID- 24084474
TI  - Vaccination with proteins involved in tick-pathogen interactions reduces vector
      infestations and pathogen infection.
AB  - Tick-borne pathogens cause diseases that greatly impact animal health and
      production worldwide. The ultimate goal of tick vaccines is to protect against
      tick-borne diseases through the control of vector infestations and reducing
      pathogen infection and transmission. Tick genetic traits are involved in vector
      pathogen interactions and some of these molecules such as Subolesin (SUB) have
      been shown to protect against vector infestations and pathogen infection. Based
      on these premises, herein we characterized the efficacy of cattle vaccination
      with tick proteins involved in vector-pathogen interactions, TROSPA, SILK, and
      Q38 for the control of cattle tick, Rhipicephalus (Boophilus) microplus
      infestations and infection with Anaplasma marginale and Babesia bigemina. SUB and
      adjuvant/saline placebo were used as positive and negative controls,
      respectively. The results showed that vaccination with Q38, SILK and SUB reduced
      tick infestations and oviposition with vaccine efficacies of 75% (Q38), 62%
      (SILK) and 60% (SUB) with respect to ticks fed on placebo control cattle.
      Vaccination with TROSPA did not have a significant effect on any of the tick
      parameters analyzed. The results also showed that vaccination with Q38, TROSPA
      and SUB reduced B. bigemina DNA levels in ticks while vaccination with SILK and
      SUB resulted in lower A. marginale DNA levels when compared to ticks fed on
      placebo control cattle. The positive correlation between antigen-specific
      antibody titers and reduction of tick infestations and pathogen infection
      strongly suggested that the effect of the vaccine was the result of the antibody
      response in vaccinated cattle. Vaccination and co-infection with A. marginale and
      B. bigemina also affected the expression of genes encoding for vaccine antigens
      in ticks fed on cattle. These results showed that vaccines using tick proteins
      involved in vector-pathogen interactions could be used for the dual control of
      tick infestations and pathogen infection. 

PMID- 24084475
TI  - In ovo expression of microRNA in ventral chick midbrain.
AB  - Non-coding RNAs are additional players in regulating gene expression. Targeted in
      ovo electroporation of specific areas provides a unique tool for spatial and
      temporal control of ectopic microRNA expression. However, ventral brain
      structures like ventral midbrain are rather difficult to reach for any
      manipulations. Here, we demonstrate an efficient way to electroporate miRNA into
      ventral midbrain using thin platinum electrodes. This method offers a reliable
      way to transfect specific areas of the midbrain and a useful tool for in vivo
      studies. 

PMID- 24084476
TI  - Letter from the editor.

PMID- 24084478
TI  - Dispersive x-ray absorption studies at the Fe K-edge on the iron chalcogenide
      superconductor FeSe under pressure.
AB  - The local structure and the electronic properties of FeSe under hydrostatic
      pressure were studied by means of dispersive x-ray absorption measurements at the
      Fe K-edge. The pressure dependence of the x-ray absorption near edge structure
      features seems to follow the behavior of the superconducting transition
      temperature Tc. The local structure, that has an important impact on the
      superconducting properties, appears to fall into two regimes: the pressure
      dependence of the Fe-Fe bond distance shows a clear change in the compressibility
      at p ~ 5 GPa; in contrast, the Fe-Se bond distance decreases continuously with
      increasing pressure with a lower compressibility than the Fe-Fe bond. The results
      suggest that the pressure dependent changes in Tc of FeSe are closely related to
      the changes in local structure.

PMID- 24084477
TI  - Major depressive disorder in breast cancer: a critical systematic review of
      pharmacological and psychotherapeutic clinical trials.
AB  - BACKGROUND: While women with breast cancer often face varying levels of
      psychological distress, there is a subgroup whose symptomatology reaches a
      threshold for diagnosis of major depressive disorder (MDD). Major depressive
      disorder is known to influence patient outcomes, such as health-related quality
      of life and treatment adherence. There are no systematic reviews that evaluate
      pharmacological and psychotherapeutic treatment trials for MDD among individuals
      with breast cancer. METHODS: Two authors independently searched MEDLINE, EMBASE,
      Cochrane and Clinical Trials.gov databases through February 20, 2013 without
      language restrictions. Core journals, reference lists and citation tracking were
      also searched. Articles on breast cancer patients were included if they (1)
      included participants with a diagnosis of MDD; (2) investigated pharmacological
      or psychotherapeutic treatments for MDD compared to placebo or usual care in a
      randomized controlled trial (RCT). RESULTS: Two RCTs on antidepressant treatment
      met inclusion criteria. However, no RCTs investigating the effects of
      psychological treatments for MDD in breast cancer were identified.
      Notwithstanding the paucity of data investigating the effects of psychological
      treatments for MDD in breast cancer, numerous psychotherapeutic strategies
      targeting depressive symptoms were identified. Mianserin had significant
      antidepressant effects when compared to placebo in a 6-week, parallel-group, RCT
      of Stage I-II breast cancer in women with MDD. Desipramine and paroxetine were
      reported to be no more efficacious than placebo in a 6-week, RCT of Stage I-IV
      breast cancer in women with MDD. CONCLUSIONS: The evidence reviewed herein
      underscores the paucity of data available to guide clinicians in treatment
      decisions for MDD in individuals with breast cancer. Therefore, the treatment of
      MDD in breast cancer is primarily based on clinical experience. Some
      antidepressants (for example, paroxetine) should be avoided in women concurrently
      taking tamoxifen due to relevant interactions involving the cytochrome CYP2D6.

PMID- 24084479
TI  - Spectroscopic study on the interaction of Trypsin with Bicyclol and analogs.
AB  - The interactions between Trypsin and Bicyclol or analogs (Bifendate, I, II and
      III) were investigated by spectrophotometric methods. It was found that Bicyclol
      or analogs had strong ability to quench the intrinsic fluorescence of Trypsin by
      a static quenching procedure. The binding constants were obtained at three
      temperatures. The thermodynamics parameters reveal that the hydrophobic and
      electrostatic interactions play an important role in the interaction. Results
      showed that the microenvironments of tryptophan residue of Trypsin were disturbed
      by the analogs. Results indicated that Bifendate was the strongest quencher among
      five compounds. 

PMID- 24084480
TI  - Chemical curing in alkyd paints: an evaluation via FT-IR and NMR spectroscopies.
AB  - A study aimed at determining the time necessary for an alkyd paint to attain
      chemical curing is presented. In particular, the object of our investigation was
      an oil paint made by Winsor & Newton, namely French ultramarine (PB29) in the
      Griffin Alkyd "fast drying oil colour" series. Using this paint, we prepared
      several mock-ups on glass. These were left in the laboratory at room temperature
      in a piece of furniture with glass doors for a total of 70 days. Samples were
      taken at different times, and the changes in their composition were monitored by
      means of FT-IR and multinuclear NMR spectroscopic analyses. Since the cross
      linking reactions involved in the formation of the pictorial film mainly affect
      the amount of carbon-carbon double bonds, we monitored the decrease in allyl,
      diallyl and vinyl protons and carbons. The data obtained from the use of both
      techniques led us to conclude that, in our particular experimental conditions,
      the chemical curing of the paint layer is reached within the first 70 days, thus
      establishing the beginning of the ageing phenomena.

PMID- 24084481
TI  - First-principles study on stability and photoelectron spectroscopy of Ga(n)As2(n
      = 1-9) clusters.
AB  - The stability and photoelectron spectroscopy of the Ga(n)As2(n=1-9) clusters have
      been studied by using first-principles based on density functional theory (DFT).
      Our calculations reveal that the stabilities of the Ga(n)As2(n=1-9) clusters tend
      to increase with the increase of the number of total atoms. The calculated second
      order difference values of the binding energy show a certain law of even-odd
      alternation, and the value of the even-numbered clusters is much larger than
      those of the odd-numbered ones. The energy gap Egap also shows a certain law of
      even-odd alternation, i.e. the Egap of the even-numbered clusters is much larger
      than the odd-numbered ones. The Egap of the clusters is between 0.2 eV and 0.6
      eV, it will provide a reference for GaAs defect level research. The Ga(n)As2(n=1
      9) clusters are potential to detect and emit THz radiation due to their ground
      state vibration frequency are in THz range.

PMID- 24084482
TI  - Four new two-photon polymerization initiators with varying donor and conjugated
      bridge: synthesis and two-photon activity.
AB  - A specific series of dumbbell-shaped bis-carbazoles or bis-phenothiazines dyes
      (1, 2, 3 and 4) constructed with styrene or biphenylethyne as the pi-bridge have
      been synthesized and characterized. Detailed spectral properties including linear
      absorption, one and two-photon fluorescence properties were investigated. The
      results show that extending conjugated chain and introducing donors have
      substantial effect on their photophysical properties. Among them, two-photon
      absorption cross sections (sigma) of the four dyes in DMF determined by the Z
      scan technique are successively increased from 1 to 4 with enhancing electron
      donating ability and extending conjugated chain, but electron-donating ability
      has larger contribution to the sigma values than extending conjugated chain based
      on the comparison of small molecules (D-pi-D). Two-photon initiation
      polymerization (TPIP) microfabrication experiments have been carried out using
      compound 4 as an initiator under irradiation of 200 fs, 76 MHz femtosecond laser
      at 760 nm. The results confirm that the four dyes can be effectively used as
      organic two-photon photopolymerization initiators.

PMID- 24084483
TI  - Computational study of the vibrational spectroscopic studies, natural bond
      orbital, frontier molecular orbital and second-order non-linear optical
      properties of acetophenone thiosemicarbazone molecule.
AB  - The vibrational frequencies of acetophenone thiosemicarbazone in the ground state
      have been calculated using density functional method (B3LYP) with 6-31G(d), 6
      31G(d,p) and 6-311++G(d,p) basis sets. The analysis of natural bond orbital was
      also performed. The IR spectra were obtained and interpreted by means of
      potential energies distributions (PEDs) using MOLVIB program. In addition, the
      results show that there exist N-H...N and N-H...S hydrogen bonds in the title
      compound, which play a major role in stabilizing the molecule and are confirmed
      by the natural bond orbital analysis. The predicted NLO properties show that the
      title compound is a good candidate as second-order NLO material. In addition, the
      frontier molecular orbitals were analyzed and the crystal structure obtained by
      molecular mechanics belongs to the Pbca space group, with lattice parameters Z=8,
      a=16.0735 A, b=7.1719 A, c=7.8725 A, rho=0.808 g/cm(3).

PMID- 24084484
TI  - Halo-substituted thiosemicarbazones and their copper(II), nickel(II) complexes:
      detailed spectroscopic characterization and study of antitumour activity against
      HepG2 human hepatoblastoma cells.
AB  - Copper(II) and nickel(II) complexes of two different halogen substituted
      thiosemicarbazone ligands were synthesized. The ligands 3,4-difluoroacetophenone
      thiosemicarbazone (1) and 2-bromo-4'-chloroacetophenone thiosemicarbazone (2)
      were characterized and confirmed spectroscopically by FT-IR, FT-Raman, UV-vis and
      fluorescence spectral analysis, while the respective copper(II) complexes
      [Cu(C9H9N3F2S)2Cl2] (1a), [Cu(C9H9N3ClBrS)2Cl2] (2a) and nickel(II) complexes
      [Ni(C9H9N3F2S)2] (1b), [Ni(C9H9N3ClBrS)2] (2b) were characterized by FT-IR, UV
      vis and electron paramagnetic spectroscopy (EPR). The EPR spectra of the Cu(II)
      complexes provided the rhombic octahedral and axial symmetry of the complexes 1a
      and 2a respectively. For the complex 1a, the g values calculated as g1=2.1228,
      g2=2.0706 and g3=2.001 between 2900 and 3300 G. While for the complex 2a, a set
      of two resonance absorptions were observed. The synthesized compounds were tested
      for antitumor activity and showed that the ability to kill liver cancer cells
      significantly. Out of all the synthesized compounds, copper(II) complexes 1a and
      2a showed high cytotoxic effect on liver cancer cells with 67.51% and 42.77% of
      cytotoxicity respectively at 100 MUM.

PMID- 24084485
TI  - Luminance behavior of Ce3+ doped ZnS nanostructures.
AB  - We report the synthesis and characterization of undoped and various levels of
      Ce(3+) doped ZnS nanocrystal. The structure and size of the products were studied
      by X-ray diffraction (XRD). The existence of functional groups was identified by
      Fourier transform infrared spectrometry (FT-IR). The UV-Visible measurements
      reveal that the synthesized products are blue shifted when compared with bulk
      phase of ZnS as a result of quantum confinement effect. The PL studies show an
      enhancement in the intensity of emission band in the UV region on increased
      Ce(3+) doping. The morphology of the products was evaluated by Field emission
      scanning electron microscope (FESEM) and High resolution transmission electron
      microscopy (FESEM). The presence of Ce(3+) was confirmed by Energy dispersive
      spectral analysis (EDS). The thermal stability of pure and doped products was
      analyzed by thermo gravimetric and differential thermal analysis (TG-DTA). 

PMID- 24084486
TI  - Theoretical design and screening of alkyne bridged triphenyl zinc porphyrins as
      sensitizer candidates for dye-sensitized solar cells.
AB  - Alkyne bridged porphyrins have been proved very promising sensitizers for dye
      sensitized solar cells (DSSCs) with the highest photo-to-electric conversion
      efficiencies of 11.9% solely and 12.3% co-sensitized with other sensitizers
      achieved. Developing better porphyrin sensitizers with wider electronic
      absorption spectra to further improve the efficiencies of corresponding solar
      cells is still of great significance for the application of DSSCs. A series of
      triphenyl zinc porphyrins (ZnTriPP) differing in the nature of a pendant acceptor
      group and the conjugated bridge between the porphyrin nucleus and the acceptor
      unit were modeled and their electronic and spectral properties calculated using
      density functional theory. As compared with each other and the experimental
      results of the compounds used in DSSCs previously, the molecules with a
      relatively longer conjugative linker and a strong electron-withdrawing group such
      as cyanide adjacent to the carboxyl acid group seem to provide wider electronic
      absorption spectra and higher photo-to-electric conversion efficiencies. The dye
      candidates ZnTriPPE, ZnTriPPM, ZnTriPPQ, ZnTriPPR and ZnTriPPS designed in the
      current work were found promising to provide comparable photo-to-electric
      conversion efficiencies to the record 11.9% of the alkyne bridged porphyrin
      sensitizer YD2-o-C8 reported previously. 

PMID- 24084487
TI  - Insights from host genomics into HIV infection and disease: Identification of
      host targets for drug development.
AB  - HIV susceptibility and disease progression show a substantial degree of
      individual heterogeneity, ranging from fast progressors to long-term non
      progressors or elite controllers, that is, subjects that control infection in the
      absence of therapy. Recent years have seen a significant increase in
      understanding of the host genetic determinants of susceptibility to HIV infection
      and disease progression, driven in large part by candidate gene studies, genome
      wide association studies, genome-wide transcriptome analyses, and large-scale
      functional screens. These studies have identified common variants in host loci
      that clearly influence disease progression, characterized the scale and dynamics
      of gene and protein expression changes in response to infection, and provided the
      first comprehensive catalogue of genes and pathways involved in viral
      replication. This review highlights the potential of host genomic influences in
      antiviral therapy by pointing to promising novel drug targets but also providing
      the basis of the identification and validation of host mechanisms that might be
      susceptible targets for novel antiviral therapies. 

PMID- 24084488
TI  - Favipiravir (T-705), a novel viral RNA polymerase inhibitor.
AB  - Favipiravir (T-705; 6-fluoro-3-hydroxy-2-pyrazinecarboxamide) is an antiviral
      drug that selectively inhibits the RNA-dependent RNA polymerase of influenza
      virus. It is phosphoribosylated by cellular enzymes to its active form,
      favipiravir-ribofuranosyl-5'-triphosphate (RTP). Its antiviral effect is
      attenuated by the addition of purine nucleic acids, indicating the viral RNA
      polymerase mistakenly recognizes favipiravir-RTP as a purine nucleotide.
      Favipiravir is active against a broad range of influenza viruses, including
      A(H1N1)pdm09, A(H5N1) and the recently emerged A(H7N9) avian virus. It also
      inhibits influenza strains resistant to current antiviral drugs, and shows a
      synergistic effect in combination with oseltamivir, thereby expanding influenza
      treatment options. A Phase III clinical evaluation of favipiravir for influenza
      therapy has been completed in Japan and two Phase II studies have been completed
      in the United States. In addition to its anti-influenza activity, favipiravir
      blocks the replication of many other RNA viruses, including arenaviruses (Junin,
      Machupo and Pichinde); phleboviruses (Rift Valley fever, sandfly fever and Punta
      Toro); hantaviruses (Maporal, Dobrava, and Prospect Hill); flaviviruses (yellow
      fever and West Nile); enteroviruses (polio- and rhinoviruses); an alphavirus,
      Western equine encephalitis virus; a paramyxovirus, respiratory syncytial virus;
      and noroviruses. With its unique mechanism of action and broad range of antiviral
      activity, favipiravir is a promising drug candidate for influenza and many other
      RNA viral diseases for which there are no approved therapies. 

PMID- 24084489
TI  - Echocardiographic predictors of reverse remodeling after cardiac
      resynchronization therapy and subsequent events.
AB  - BACKGROUND: Studies of echocardiographic predictors of response after cardiac
      resynchronization therapy (CRT) have largely involved single parameters. We
      hypothesized that combining parameters would be more robust and sought to develop
      a multiparametric echocardiographic score for predicting CRT response. METHODS
      AND RESULTS: Global longitudinal strain of left ventricle was added to standard
      echocardiographic measurements in 334 consecutive patients (224 men; mean, 65+/
      12 years) who underwent baseline echocardiography before CRT and underwent follow
      up echocardiograms at 1 year. Regression analysis was performed to create an
      echocardiographic score for prediction of LV reverse remodeling (defined as >=15%
      reduction in the LV end-systolic volume). Cox proportional hazards models were
      used to identify the association of the score with death, transplantation or LV
      assist device implantation, and heart failure hospitalization during 57+/-22
      months of follow-up. LV reverse remodeling (n=161; 48%) was associated with pre
      CRT LV end-diastolic dimension index <3.1 cm/m(2), global longitudinal strain of
      left ventricle <-7%, left atrial area <26 cm(2), right ventricular end-diastolic
      area index <10.0 cm(2)/m(2), right atrial area <20 cm(2), and right ventricular
      fractional area change >=35%. Combination of these into an echocardiographic
      score allowed prediction of LV reverse remodeling with a sensitivity of 84% and a
      specificity of 79%. During follow-up, there were 134 deaths, 18 heart
      transplantations/LV assist device implantations, and 93 heart failure admissions.
      The score was associated with heart failure admission, heart transplantation/LV
      assist device, or death (hazard ratio, 0.97; 95% confidence interval, 0.95-0.98;
      P<0.001) and all-cause death (hazard ratio, 0.97; 95% confidence interval, 0.96
      0.98; P<0.001), independent of age, sex, ischemic cause, and initial functional
      class. CONCLUSIONS: A multiparametric echocardiographic score is helpful in
      selecting patients likely to undergo reverse remodeling after CRT and predicts
      clinical outcomes.

PMID- 24084490
TI  - Spectrum of aortic valve abnormalities associated with aortic dilation across age
      groups in Turner syndrome.
AB  - BACKGROUND: Congenital aortic valve fusion is associated with aortic dilation,
      aneurysm, and rupture in girls and women with Turner syndrome. Our objective was
      to characterize aortic valve structure in subjects with Turner syndrome and to
      determine the prevalence of aortic dilation and valve dysfunction associated with
      different types of aortic valves. METHODS AND RESULTS: The aortic valve and
      thoracic aorta were characterized by cardiovascular MRI in 208 subjects with
      Turner syndrome in an institutional review board-approved natural history study.
      Echocardiography was used to measure peak velocities across the aortic valve and
      the degree of aortic regurgitation. Four distinct valve morphologies were
      identified: tricuspid aortic valve, 64% (n=133); partially fused aortic valve,
      12% (n=25); bicuspid aortic valve, 23% (n=47); and unicuspid aortic valve, 1%
      (n=3). Age and body surface area were similar in the 4 valve morphology groups.
      There was a significant trend, independent of age, toward larger body surface
      area-indexed ascending aortic diameters with increasing valve fusion. Ascending
      aortic diameters were (mean+/-SD) 16.9+/-3.3, 18.3+/-3.3, and 19.8+/-3.9 mm/m(2)
      (P<0.0001) for tricuspid aortic valve, partially fused aortic valve, and bicuspid
      aortic valve+unicuspid aortic valve, respectively. Partially fused aortic valve,
      bicuspid aortic valve, and unicuspid aortic valve were significantly associated
      with mild aortic regurgitation and elevated peak velocities across the aortic
      valve. CONCLUSIONS: Aortic valve abnormalities in Turner syndrome occur with a
      spectrum of severity and are associated with aortic root dilation across age
      groups. Partial fusion of the aortic valve, traditionally regarded as an acquired
      valve problem, had an equal age distribution and was associated with an increased
      ascending aortic diameters.

PMID- 24084491
TI  - Culturing and maintaining Clostridium difficile in an anaerobic environment.
AB  - Clostridium difficile is a Gram-positive, anaerobic, sporogenic bacterium that is
      primarily responsible for antibiotic associated diarrhea (AAD) and is a
      significant nosocomial pathogen. C. difficile is notoriously difficult to isolate
      and cultivate and is extremely sensitive to even low levels of oxygen in the
      environment. Here, methods for isolating C. difficile from fecal samples and
      subsequently culturing C. difficile for preparation of glycerol stocks for long
      term storage are presented. Techniques for preparing and enumerating spore stocks
      in the laboratory for a variety of downstream applications including microscopy
      and animal studies are also described. These techniques necessitate an anaerobic
      chamber, which maintains a consistent anaerobic environment to ensure proper
      conditions for optimal C. difficile growth. We provide protocols for transferring
      materials in and out of the chamber without causing significant oxygen
      contamination along with suggestions for regular maintenance required to sustain
      the appropriate anaerobic environment for efficient and consistent C. difficile
      cultivation. 

PMID- 24084492
TI  - Sleep apnea and cardiovascular risk.
AB  - Sleep apnea is evident in approximately 10% of adults in the general population,
      but in certain cardiovascular diseases, and in particular those characterized by
      sodium and water retention, its prevalence can exceed 50%. Although sleep apnea
      is not as yet integrated into formal cardiovascular risk assessment algorithms,
      there is increasing awareness of its importance in the causation or promotion of
      hypertension, coronary artery disease, heart failure, atrial arrhythmias, and
      stroke, and thus, not surprisingly, as a predictor of premature cardiovascular
      death. Sleep apnea manifests as two principal phenotypes, both characterized by
      respiratory instability: obstructive (OSA), which arises when sleep-related
      withdrawal of respiratory drive to the upper airway dilator muscles is
      superimposed upon a narrow and highly compliant airway predisposed to collapse,
      and central (CSA), which occurs when the partial pressure of arterial carbon
      dioxide falls below the apnea threshold, resulting in withdrawal of central drive
      to respiratory muscles. The present objectives are to: (1) review the
      epidemiology and patho-physiology of OSA and CSA, with particular emphasis on the
      role of renal sodium retention in initiating and promoting these processes, and
      on population studies that reveal the long-term consequences of untreated OSA and
      CSA; (2) illustrate mechanical, autonomic, chemical, and inflammatory mechanisms
      by which OSA and CSA can increase cardiovascular risk and event rates by
      initiating or promoting hypertension, atherosclerosis, coronary artery disease,
      heart failure, arrhythmias, and stroke; (3) highlight insights from randomized
      trials in which treating sleep apnea was the specific target of therapy; (4)
      emphasize the present lack of evidence that treating sleep apnea reduces
      cardiovascular risk and the current clinical equipoise concerning treatment of
      asymptomatic patients with sleep apnea; and (5) consider clinical implications
      and future directions of clinical research and practice. 

PMID- 24084493
TI  - Transgenic barley: a prospective tool for biotechnology and agriculture.
AB  - Barley (Hordeum vulgare L.) is one of the founder crops of agriculture, and today
      it is the fourth most important cereal grain worldwide. Barley is used as malt in
      brewing and distilling industry, as an additive for animal feed, and as a
      component of various food and bread for human consumption. Progress in stable
      genetic transformation of barley ensures a potential for improvement of its
      agronomic performance or use of barley in various biotechnological and industrial
      applications. Recently, barley grain has been successfully used in molecular
      farming as a promising bioreactor adapted for production of human therapeutic
      proteins or animal vaccines. In addition to development of reliable
      transformation technologies, an extensive amount of various barley genetic
      resources and tools such as sequence data, microarrays, genetic maps, and
      databases has been generated. Current status on barley transformation
      technologies including gene transfer techniques, targets, and progeny
      stabilization, recent trials for improvement of agricultural traits and
      performance of barley, especially in relation to increased biotic and abiotic
      stress tolerance, and potential use of barley grain as a protein production
      platform have been reviewed in this study. Overall, barley represents a promising
      tool for both agricultural and biotechnological transgenic approaches, and is
      considered an ancient but rediscovered crop as a model industrial platform for
      molecular farming. 

PMID- 24084494
TI  - Retracting the ear: a hands-free approach.

PMID- 24084495
TI  - Mutations in the mevalonate kinase (MVK) gene cause nonsyndromic retinitis
      pigmentosa.
AB  - OBJECTIVE: Retinitis pigmentosa (RP) is a clinically and genetically
      heterogeneous disorder characterized by night blindness and peripheral vision
      loss, and in many cases leads to blindness. Despite extensive knowledge about
      genes involved in the pathogenesis of RP, the genetic cause remains elusive in
      many patients. In this study, we aimed to identify novel genes that are involved
      in the cause of RP. DESIGN: We present a case series with mutations in the
      mevalonate kinase (MVK) gene. PARTICIPANTS: A total of 769 patients with
      nonsyndromic RP and 174 Dutch control individuals participated in this study.
      METHODS: Exome sequencing analysis was performed in a proband of Dutch origin who
      was initially diagnosed with nonsyndromic autosomal recessive RP. Mutations in
      MVK were identified and subsequently tested for segregation within the patient's
      family and screened in a large cohort of patients with genetically unsolved RP.
      Patients with mutations underwent extensive clinical reexamination. MAIN OUTCOME
      MEASURES: Digital fundus photography, spectral-domain optical coherence
      tomography (OCT), and fundus autofluorescence analysis were performed in patients
      with MVK mutations. Mevalonate kinase (MK) enzyme activity was analyzed in
      cultured lymphoblastoid cells, and mevalonic acid levels were measured in urine
      samples. RESULTS: Exome variant filtering and prioritization led to the
      identification of compound heterozygous mutations in MVK (p.I268T and p.A334T) in
      the proband and her affected brother. Screening of our nonsyndromic RP patient
      cohort revealed an additional individual who was homozygous for the p.A334T
      alteration. Clinical reevaluation of all 3 patients showed a classic form of RP
      with variable extraocular symptoms, such as history of recurrent childhood
      febrile crises in 2 patients, mild ataxia in 1, and renal failure in 1. All 3
      affected individuals showed a significantly decreased MK activity and highly
      elevated levels of urinary mevalonic acid. CONCLUSIONS: Although the MK activity
      in cells and mevalonic acid concentrations in urine are strongly aberrant and
      comparable to that in patients with systemic mevalonate kinase deficiency (MKD),
      only mild clinical symptoms related to this syndrome were observed in our
      patients. In the current article, we add another phenotype to the spectrum of
      diverging disorders associated with mutations in MVK.

PMID- 24084497
TI  - Intravitreal Aflibercept Injection for Macular Edema Resulting from Central
      Retinal Vein Occlusion: One-Year Results of the Phase 3 GALILEO Study.
AB  - PURPOSE: To evaluate the efficacy and safety of intravitreal aflibercept
      injections for treatment of macular edema secondary to central retinal vein
      occlusion (CRVO). DESIGN: A randomized, multicenter, double-masked phase 3 study.
      PARTICIPANTS: A total of 177 treatment-naive patients with macular edema
      secondary to CRVO were randomized in a 3:2 ratio. METHODS: Patients received
      either 2-mg intravitreal aflibercept or sham injections every 4 weeks for 20
      weeks. From week 24 to 48, the aflibercept group received aflibercept as needed
      (pro re nata [PRN]), and the sham group continued receiving sham injections. MAIN
      OUTCOME MEASURES: The primary efficacy end point was the proportion of patients
      who gained 15 letters or more in best-corrected visual acuity (BCVA) at week 24.
      This study reports week 52 results including the proportion of patients who
      gained 15 letters or more in BCVA and the mean change from baseline BCVA and
      central retinal thickness. Efficacy end points at week 52 were all exploratory.
      RESULTS: At week 52, the mean percentage of patients gaining 15 letters or more
      was 60.2% in the aflibercept group and 32.4% in the sham group (P = 0.0004).
      Aflibercept patients, compared with sham patients, had a significantly higher
      mean improvement in BCVA (+16.9 letters vs. +3.8 letters, respectively) and
      reduction in central retinal thickness (-423.5 MUm vs. -219.3 MUm, respectively)
      at week 52 (P < 0.0001 for both). Aflibercept patients received a mean of 2.5
      injections (standard deviation, 1.7 injections) during PRN dosing. The most
      common ocular adverse events in the aflibercept group were related to the
      injection procedure or the underlying disease, and included macular edema
      (33.7%), increased intraocular pressure (17.3%), and eye pain (14.4%).
      CONCLUSIONS: Treatment with intravitreal aflibercept provided significant
      functional and anatomic benefits after 52 weeks as compared with sham. The
      improvements achieved after 6 monthly doses at week 24 largely were maintained
      until week 52 with as-needed dosing. Intravitreal aflibercept generally was well
      tolerated.

PMID- 24084496
TI  - Risk of geographic atrophy in the comparison of age-related macular degeneration
      treatments trials.
AB  - PURPOSE: To describe risk factors for geographic atrophy (GA) in the Comparison
      of Age-related Macular Degeneration Treatments Trials (CATT). DESIGN: Cohort
      within a randomized clinical trial. PARTICIPANTS: We analyzed 1024 CATT patients
      with no GA visible on color fundus photographs (CFPs) and/or fluorescein
      angiograms (FAs) at enrollment. METHODS: Eyes were assigned to ranibizumab (0.5
      mg) or bevacizumab (1.25 mg) treatment and to a 2-year monthly or pro re nata
      (PRN) injection regimen, or monthly injections for 1 year and PRN for 1 year.
      Demographic, genetic, and baseline ocular characteristics and lesion features of
      CFP/FA and optical coherence tomography (OCT) were evaluated as risk factors for
      GA through 2 years of follow-up. Time-dependent Cox proportional hazard models
      were used to estimate adjusted hazard ratios (aHRs). MAIN OUTCOME MEASURES:
      Development of GA. RESULTS: By 2 years, GA developed in 187 of 1024 patients
      (18.3%). Baseline risk factors for GA development included baseline visual acuity
      (VA) <=20/200 (aHR, 2.65; 95% confidence interval [CI], 1.43-4.93), retinal
      angiomatous proliferation (RAP; aHR, 1.69; 95% CI, 1.16-2.47), GA in the fellow
      eye (aHR, 2.07; 95% CI, 1.40-3.08), and intraretinal fluid at the foveal center
      (aHR, 2.10; 95% CI, 1.34-3.31). Baseline factors associated with lower risk for
      GA development included blocked fluorescence (aHR, 0.49; 95% CI, 0.29-0.82), OCT
      measurements of subretinal fluid thickness of >25 MU (aHR, 0.52; 95% CI, 0.35
      0.78), subretinal tissue complex thickness of >275 compared with <=75 MU (aHR,
      0.31; 95% CI, 0.19-0.50), and vitreomacular attachment (aHR, 0.55; 95% CI, 0.31
      0.97). Ranibizumab compared with bevacizumab had a higher risk (aHR, 1.43; 95%
      CI, 1.06-1.93), and monthly dosing had a higher risk (aHR, 1.59; 95% CI, 1.17
      2.16) than PRN dosing. There were no strong associations between development of
      GA and the presence of risk alleles for CFH, ARMS 2, HTRA1, C3, or TLR3.
      CONCLUSIONS: Approximately one fifth of CATT patients developed GA within 2 years
      of treatment. Independent baseline risk factors included poor VA, RAP, foveal
      intraretinal fluid, monthly dosing, and treatment with ranibizumab. Anti-vascular
      endothelial growth factor therapy may have a role in the development of GA.

PMID- 24084498
TI  - Anterior capsulotomy integrity after femtosecond laser-assisted cataract surgery.
AB  - OBJECTIVE: To compare the incidence of anterior capsular tears after femtosecond
      laser-assisted cataract surgery (FLACS) versus phacoemulsification cataract
      surgery (PCS) and to assess the ultrastructural features of anterior capsulotomy
      specimens (FLACS and PCS) using electron microscopy. DESIGN: Prospective,
      multicenter, comparative cohort case series. PARTICIPANTS: Consecutive patients
      undergoing FLACS or PCS. METHODS: A prospective cohort study of all patients (n =
      1626) undergoing FLACS or PCS by 2 surgeons from centers A and B was undertaken
      to compare the incidence of anterior capsule tears. Anterior lens capsules were
      collected by 4 surgeons from centers A, B, C, and D using 3 different
      commercially available femtosecond platforms, each with latest version upgrades.
      Lens capsule tissue was prepared for scanning electron microscopy (SEM) using a
      total of 10 samples for patients undergoing PCS, and 40 samples for patients
      undergoing FLACS. MAIN OUTCOME MEASURES: Incidence of anterior capsule tear and
      comparative ultrastructural features of capsular samples from both PCS and FLACS
      cases. RESULTS: There was a significantly increased rate of anterior capsule
      tears in the FLACS group (15/804 [1.87%]) when compared with the PCS group (1/822
      [0.12%]; P = 0.0002, Fisher exact test). In 7 cases, the anterior capsule tear
      extended to the posterior capsule. Because all cases had occurred in complete
      capsulotomy, the integrity of the anterior capsule was questioned in the FLACS
      group. Subsequent SEM sampling showed irregularity at the capsule margin, as well
      as multiple apparently misplaced laser pits in normal parts of the tissue.
      Aberrant pits were approximately 2 to 4 MUm apart and occurred at a range of 10
      to 100 MUm radially from the capsule edge. CONCLUSIONS: Laser anterior
      capsulotomy integrity seems to be compromised by postage-stamp perforations and
      additional aberrant pulses, possibly because of fixational eye movements. This
      can lead to an increased rate of anterior capsule tears, and extra care should be
      taken during surgery after femtosecond laser pretreatment has been performed. A
      learning curve may account for some of the increased complication rate with
      FLACS. However, the SEM features raise safety concerns for capsular integrity
      after FLACS and warrant further investigation.

PMID- 24084499
TI  - High prevalence of peripheral retinal vascular anomalies in family members of
      patients with familial exudative vitreoretinopathy.
AB  - OBJECTIVE: To describe the prevalence and severity of familial exudative
      vitreoretinopathy (FEVR) in asymptomatic relatives of known symptomatic FEVR
      patients. DESIGN: Uncontrolled and retrospective case series at a single tertiary
      referral vitreoretinal practice. PARTICIPANTS: A total of 148 eyes of 74 subjects
      were studied. METHODS: A retrospective chart review was conducted of patients
      with a diagnosis of FEVR between January 2011 and January 2013 at a single
      tertiary care retina practice. Data were collected from patient charts, including
      sex, gestational age at birth, age at presentation, referring diagnosis, family
      history, prior ocular surgery, clinical presentation, and diagnostic imaging in
      each eye. Inclusion criteria included confirmed clinical diagnosis of FEVR in
      patients referred to our clinic for evaluation of decreased vision. Patients were
      excluded if a definitive diagnosis of FEVR could not be made. MAIN OUTCOME
      MEASURES: Clinical and angiographic findings. RESULTS: A total of 74 subjects
      from 17 separate families met the inclusion criteria for this study. There were
      an average of 4.4 subjects per family included in this study. The cohort was 55%
      male and included 17 patients and 57 family members who agreed to undergo
      genotyping, examination, and diagnostic imaging. Forty-three percent of FEVR
      patients had detectable mutations in FZD4, NDP, or TSPAN12. Only 8% of the cohort
      reported a positive family history of FEVR in a first-degree relative. Among the
      index patients, 76% had clinical stage 3, 4, or 5 FEVR and 24% had stage 1 or 2
      FEVR. Among the asymptomatic family members screened, 58% demonstrated clinical
      or angiographic findings consistent with stage 1 or 2 FEVR and 21% demonstrated
      clinical or angiographic findings consistent with stage 3, 4, or 5 FEVR.
      CONCLUSIONS: Asymptomatic family members of FEVR patients frequently have early
      manifestations of FEVR (stage 1 or 2). Early-stage FEVR may progress to more
      advanced stages, which can result in vision loss. These data support the use of
      angiographic screening and clinical examination in immediate relatives of
      patients with symptomatic FEVR.

PMID- 24084500
TI  - Intravitreal aflibercept injection for neovascular age-related macular
      degeneration: ninety-six-week results of the VIEW studies.
AB  - PURPOSE: To determine efficacy and safety of intravitreal aflibercept in patients
      with neovascular age-related macular degeneration (AMD) during a second year of
      variable dosing after a first-year fixed-dosing period. DESIGN: Two randomized,
      double-masked, active-controlled, phase 3 trials. PARTICIPANTS: Two thousand four
      hundred fifty-seven patients with neovascular AMD. METHODS: From baseline to week
      52, patients received 0.5 mg intravitreal ranibizumab every 4 weeks (Rq4), 2 mg
      aflibercept every 4 weeks (2q4), 0.5 mg aflibercept every 4 weeks (0.5q4), or 2
      mg aflibercept every 8 weeks (2q8) after 3 monthly injections. During weeks 52
      through 96, patients received their original dosing assignment using an as-needed
      regimen with defined retreatment criteria and mandatory dosing at least every 12
      weeks. MAIN OUTCOME MEASURES: Proportion of eyes at week 96 that maintained best
      corrected visual acuity (BCVA; lost <15 letters from baseline); change from
      baseline in BCVA. RESULTS: Proportions of eyes maintaining BCVA across treatments
      were 94.4% to 96.1% at week 52 and 91.5% to 92.4% at week 96. Mean BCVA gains
      were 8.3 to 9.3 letters at week 52 and 6.6 to 7.9 letters at week 96. Proportions
      of eyes without retinal fluid decreased from week 52 (60.3% to 72.4%) to week 96
      (44.6% to 54.4%), and more 2q4 eyes were without fluid at weeks 52 and 96 than
      Rq4 eyes (difference of 10.4% [95% confidence interval {CI}, 4.9-15.9] and 9.0%
      [95% CI, 3.0-15.1]). Patients received on average 16.5, 16.0, 16.2, and 11.2
      injections over 96 weeks and 4.7, 4.1, 4.6, and 4.2 injections during weeks 52
      through 96 in the Rq4, 2q4, 0.5q4, and 2q8 groups, respectively. The number of
      injections during weeks 52 through 96 was lower in the 2q4 and 2q8 groups versus
      the Rq4 group (differences of -0.64 [95% CI, -0.89 to -0.40] and -0.55 [95% CI, 
      0.79 to -0.30]; P < 0.0001, post hoc analysis). Incidences of Antiplatelet
      Trialists' Collaboration-defined arterial thromboembolic events were similar
      across groups (2.4% to 3.8%) from baseline to week 96. CONCLUSIONS: All
      aflibercept and ranibizumab groups were equally effective in improving BCVA and
      preventing BCVA loss at 96 weeks. The 2q8 aflibercept group was similar to
      ranibizumab in visual acuity outcomes during 96 weeks, but with an average of 5
      fewer injections. Small losses at 96 weeks in the visual and anatomic gains seen
      at 52 weeks in all arms were in the range of losses commonly observed with
      variable dosing.

PMID- 24084501
TI  - Evaluation of telemedicine for screening of diabetic retinopathy in the Veterans
      Health Administration.
AB  - OBJECTIVE: To explore the cost-effectiveness of telemedicine for the screening of
      diabetic retinopathy (DR) and identify changes within the demographics of a
      patient population after telemedicine implementation. DESIGN: A retrospective
      medical chart review (cohort study) was conducted. PARTICIPANTS: A total of 900
      type 1 and type 2 diabetic patients enrolled in a medical system with a
      telemedicine screening program for DR. METHODS: The cost-effectiveness of the DR
      telemedicine program was determined by using a finite-horizon, discrete time,
      discounted Markov decision process model populated by parameters and testing
      frequency obtained from patient records. The model estimated the progression of
      DR and determined average quality-adjusted life years (QALYs) saved and average
      additional cost incurred by the telemedicine screening program. MAIN OUTCOME
      MEASURES: Diabetic retinopathy, macular edema, blindness, and associated QALYs.
      RESULTS: The results indicate that telemedicine screening is cost-effective for
      DR under most conditions. On average, it is cost-effective for patient
      populations of >3500, patients aged <80 years, and all racial groups. Observable
      trends were identified in the screening population since the implementation of
      telemedicine screening: the number of known DR cases has increased, the overall
      age of patients receiving screenings has decreased, the percentage of nonwhites
      receiving screenings has increased, the average number of miles traveled by a
      patient to receive a screening has decreased, and the teleretinal screening
      participation is increasing. CONCLUSIONS: The current teleretinal screening
      program is effective in terms of being cost-effective and increasing population
      reach. Future screening policies should give consideration to the age of patients
      receiving screenings and the system's patient pool size because our results
      indicate it is not cost-effective to screen patients aged older than 80 years or
      in populations with <3500 patients.

PMID- 24084502
TI  - A perspective on laboratory utilization management from Canada.
AB  - Utilization, particularly in chemistry and molecular testing, is growing rapidly
      in Canada at a time when laboratory budgets are shrinking. Canadian laboratories
      face particular challenges as the prevailing funding model limits the scope for
      new revenue generation. Aggressive and coordinated interventions to reduce over
      utilization will be necessary to ensure the long-term viability of the current
      system. 

PMID- 24084503
TI  - Molecular characterization of 7 new alpha-1 anti-trypsin (A1AT) variants
      including two with an associated deficient phenotype.

PMID- 24084504
TI  - A clinician's perspective on laboratory utilization management.
AB  - BACKGROUND: Excessive laboratory utilization is a common problem in the hospital
      setting. Physicians control up to 80% of healthcare costs and wield great
      influence. METHODS: This review article describes reasons for overutilization of
      labs and recommends interventional strategies to change clinician ordering
      behavior. RESULTS: Powerful factors exist that encourage overutilization,
      including fear of missing a diagnosis, provider inexperience, peer pressure,
      financial rewards, practice inertia, and fear of legal punishment. Features of
      automated order entry, such as bundling and "daily until discontinued" options
      contribute to wasteful ordering behavior. CONCLUSION: The most successful and
      long-lasting interventions are multi-faceted and have included a combination of
      education, feedback and audit, and administrative changes. The support of senior
      physicians and top administration is critical to the success of any initiative
      and ideally, interventions should be original from a multi-disciplinary committee
      of respected individuals.

PMID- 24084505
TI  - Calculating cost savings in utilization management.
AB  - A major motivation for managing the utilization of laboratory testing is to
      reduce the cost of medical care. For this reason it is important to understand
      the basic principles of cost accounting in the clinical laboratory. The process
      of laboratory testing includes three distinct components termed the pre-analytic,
      analytic and post-analytic phases. Utilization management efforts may impact the
      cost structure of these three phases in different ways depending on the specific
      details of the initiative. Estimates of cost savings resulting from utilization
      management programs reported in the literature have often been fundamentally
      flawed due to a failure to understand basic concepts such as the difference
      between laboratory costs versus charges and the impact of reducing laboratory
      test volumes on the average versus marginal cost structure in the laboratory.
      This article will provide an overview of basic cost accounting principles in the
      clinical laboratory including both job order and process cost accounting.
      Specific examples will be presented to illustrate these concepts in various
      different scenarios. 

PMID- 24084506
TI  - Genetic testing utilization and the role of the laboratory genetic counselor.
AB  - Laboratory genetic counselors within hospital laboratories and genetic testing
      laboratories have an important role in increasing the appropriate utilization of
      genetic tests. This service is becoming more important as genetic testing becomes
      more complex and the demand for genetic testing in healthcare increases.
      Additionally genetic tests are among the most expensive assays in the clinical
      laboratory test catalog. Laboratory genetic counselors are able to increase
      genetic test utilization through review and assessment of the appropriateness of
      the ordered testing, developing protocols, and by increasing communication with
      ordering providers. 

PMID- 24084507
TI  - The role of informatics and decision support in utilization management.
AB  - Information systems provide a critical link between clinical laboratories and the
      clinicians and patients they serve. Strategic deployment of informatics resources
      can enable a wide array of utilization initiatives and can substantially improve
      the appropriateness of test selection and results interpretation. In this
      article, we review information systems including computerized provider order
      entry (CPOE) systems, laboratory information systems (LISs), electronic health
      records (EHRs), laboratory middleware, knowledge management systems and systems
      for data extraction and analysis, and describe the role that each can play in
      utilization management. We also discuss specific utilization strategies that
      laboratories can employ within these systems, citing examples both from our own
      institution and from the literature. Finally, we review how emerging applications
      of decision support technologies may help to further refine test utilization,
      "personalize" laboratory diagnosis, and enhance the diagnostic value of
      laboratory testing. 

PMID- 24084508
TI  - Utilization management in the changing health-care environment.
AB  - US health-care costs are growing at an alarming rate. "Value-based" payment
      models that hold providers accountable for outcomes and costs of care are
      becoming more prevalent. In these arrangements, provider groups will be
      accountable for the costs of lab tests, many of which have traditionally been
      revenue-generating. "Stewardship" programs aimed at newer, high-cost specialized
      tests, decision support on more routine tests, variation reporting, and
      incentives are familiar tactics that will need to be deployed in this new
      context. 

PMID- 24084509
TI  - Appetitive, dietary and health effects of almonds consumed with meals or as
      snacks: a randomized, controlled trial.
AB  - BACKGROUND/OBJECTIVES: Snacks contribute toward a significant proportion of human
      total daily energy intake. This study investigated the effects of almonds, a
      satiating and nutrient-rich, common snack, on postprandial glycemia, appetite,
      short-term body weight and fasting blood parameters when consumed with meals or
      alone as a snack. METHODS: This was a 4-week randomized, parallel-arm study that
      entailed consuming almonds (43 g/day) with breakfast (BF) or lunch (LN), alone as
      a morning (MS) or afternoon (AS) snack or no almonds (CL). Participants (N=137)
      with increased risk for type 2 diabetes completed an oral glucose tolerance test
      (OGTT) and acute-feeding session at baseline, followed by almond consumption for
      4 weeks before repeating the OGTT and acute-feeding trials. Anthropometric,
      biochemical and appetite responses were assessed. RESULTS: Almonds lowered serum
      glucose responses postprandially. Effects were most prominent in the snack
      groups. Almonds, consumed as snacks, also reduced hunger and desire to eat during
      the acute-feeding session. After 4 weeks, anthropometric measurements and fasting
      blood biochemistries did not differ from the control group or across intervention
      groups. Without specific guidance, daily energy intake was reduced to compensate
      for energy from the provided almonds. Dietary monounsaturated fat and alpha
      tocopherol intakes were significantly increased in all almond groups. CONCLUSION:
      Almonds provide post-ingestive metabolic and appetitive benefits and did not
      increase the risk for weight gain. This suggests that almonds may be a healthful
      snack option.

PMID- 24084510
TI  - Acute effects of violent video-game playing on blood pressure and appetite
      perception in normal-weight young men: a randomized controlled trial.
AB  - Watching television and playing video game being seated represent sedentary
      behaviours and increase the risk of weight gain and hypertension. We investigated
      the acute effects of violent and non-violent video-game playing on blood pressure
      (BP), appetite perception and food preferences. Forty-eight young, normal-weight
      men (age: 23.1+/-1.9 years; body mass index: 22.5+/-1.9 kg/m(2)) participated in
      a three-arm, randomized trial. Subjects played a violent video game, a
      competitive, non-violent video game or watched TV for 1 h. Measurements of BP,
      stress and appetite perception were recorded before a standardized meal (~300
      kcal) and then repeated every 15 min throughout the intervention. Violent video
      game playing was associated with a significant increase in diastolic BP (Delta+/
      s.d.=+7.5+/-5.8 mm Hg; P=0.04) compared with the other two groups. Subjects
      playing violent video games felt less full (P=0.02) and reported a tendency
      towards sweet food consumption. Video games involving violence appear to be
      associated with significant effects on BP and appetite perceptions compared with
      non-violent gaming or watching TV. 

PMID- 24084511
TI  - Bone mineral changes after lactation in Gambian women accustomed to a low calcium
      intake.
AB  - BACKGROUND/OBJECTIVES: Previous studies in Gambian women with a low calcium
      intake have described decreases in whole-body and regional bone mineral content
      (BMC) and areal bone mineral density (aBMD) during the first year of lactation.
      The aim of this study was to examine whether these effects are reversed after
      lactation. SUBJECTS/METHODS: Thirty-three Gambian women who had a previous dual
      energy X-ray absorptiometry (DXA) scan at 52 weeks lactation (L52) were invited
      to participate in a follow-up study when neither pregnant nor lactating (NPNL)
      for >=3 months and/or when 52 weeks postpartum in a subsequent lactation (F52).
      Whole body, lumbar spine and hip bone mineral were measured by DXA. Anthropometry
      and dietary assessments were also conducted. Repeated-measures analysis of
      covariance was used to determine differences from L52 at NPNL and F52. RESULTS:
      Twenty-eight women were scanned at NPNL and 20 at F52. The mean+/-s.d. calcium
      intake of the 33 women at NPNL and F52 was 360+/-168 mg/day. BMC, aBMD and size
      adjusted BMC (SA-BMC) at all sites were higher at NPNL than L52. Percent
      increases in SA-BMC (mean+/-s.e.m.) were significant (P<0.0001): whole body=2.7+/
      0.4%; lumbar spine=4.9+/-1.0%; total hip=3.7+/-1.0%. There were no significant
      differences in any measurements between the two lactation time points (L52 and
      F52). CONCLUSIONS: This study of Gambian women with low calcium intakes
      demonstrates that bone mineral mobilised during lactation is recovered after
      lactation. Successive periods of long lactation are not associated with
      progressive skeletal depletion.

PMID- 24084512
TI  - Associations of serum n-3 and n-6 polyunsaturated fatty acids with
      echocardiographic measures among older adults: the Hoorn Study.
AB  - BACKGROUND/OBJECTIVES: Lower circulating polyunsaturated fatty acids (PUFAs) may
      induce loss of heart function. We investigated whether lower concentrations of n
      3 and n-6 PUFAs were associated with less favourable echocardiographic measures
      and higher heart rate in older Caucasians, cross-sectionally and after 7 years of
      follow-up. SUBJECTS/METHODS: We used data from the Hoorn Study, a population
      based cohort. Cross-sectional data were available for 621 participants and
      longitudinal data for 336 participants. Mean age was 68.6+/-6.8 years at
      baseline. We performed linear regression analyses using n-3 and n-6 PUFAs
      quartiles-assayed by gas liquid chromatography-with left ventricular ejection
      fraction (LVEF), left ventricular mass index, left atrial volume index and heart
      rate. RESULTS: In multivariable analyses (regression coefficient (95% confidence
      interval)), the lowest eicosapentaenoic acid and docosahexaenoic acid quartiles
      compared with the highest quartiles were cross-sectionally associated with lower
      LVEF. Lower eicosapentaenoic acid and docosahexaenoic acid concentrations were
      associated with higher heart rate: 3.7 b.p.m. (1.5, 6.0; P for trend <0.001) and
      3.4 b.p.m. (1.2, 5.6; P for trend 0.001), respectively. Multivariate longitudinal
      analyses showed a significant trend across quartiles for alpha-linolenic acid in
      relation to LVEF. The lowest linoleic acid quartile was significantly associated
      with a decreased LVEF of -4.0% compared with the highest quartile. CONCLUSIONS:
      This study found no strong evidence of longitudinal associations of
      eicosapentaenoic acid and docosahexaenoic acid with echocardiographic measures,
      however, lower concentrations of alpha-linolenic acid and linoleic acid were
      associated with decreased LVEF. These results provide evidence for a potential
      protective role of alpha-linolenic acid and linoleic acid in relation to systolic
      function.

PMID- 24084513
TI  - Vitamin D supplementation in a healthy, middle-aged population: actual practices
      based on data from a French comprehensive regional health-care database.
AB  - BACKGROUND/OBJECTIVES: The debate surrounding recommendations for vitamin D
      supplementation in middle-aged patients (that is, 20-60 years of age) with low
      serum concentrations of 25-hydroxyvitamin D (25(OH)D) is growing. Our aim was to
      describe practices regarding vitamin D supplementation in this age group, which
      are basically unknown. SUBJECTS/METHODS: We performed an analysis using
      exhaustive reimbursement data from the individuals in Rhone-Alpes area, a French
      region regrouping more than 6 million of inhabitants. The data were collected
      from the French Insurance Health-care System. Patients who were 20-60 years of
      age, had no severe comorbidities, had a 25(OH)D assay between 1 December 2008 and
      31 January 2009 were identified. Those who received a subsequent prescription for
      vitamin D were included in this analysis. We described patterns of vitamin D
      supplementation by frequency and daily dose. RESULTS: The sample in this study
      included 1311 patients. The mean age was 47.7 years (s.d.: 9.5) and the median
      age was 50.2 years. Most of the participants (that is, 85.9%) were women. A total
      of 372 distinct prescription patterns for vitamin D supplementation were
      observed. The two most frequent (that is, 32.6% in total) involved a unique
      dispensation of a high dose of either 200,000 (17.5%) or 100,000 IU (15.1%). Most
      prescribed supplements were based on vitamin D3 (65%), and the most prescribed
      forms were high dose ampoules (81.6%). Only 48.9% of the participants were given
      a maintenance prescription after the initial loading phase. CONCLUSIONS: Our
      results reveal a significant variability in the prescriptions for vitamin D
      supplementation from physicians in the French population. Moreover, less than
      half of the patients receive maintenance therapy after the initial loading phase
      of supplementation.

PMID- 24084514
TI  - Birth weight, rapid weight gain in infancy and markers of overweight and obesity
      in childhood.
AB  - OBJECTIVE: To evaluate the relationship between birth weight and rapid weight
      gain in infancy and markers of overweight/obesity in childhood, using different
      cutoff values for rapid weight gain. SUBJECTS/METHODS: Cross-sectional study
      involving 98 5-year old pre-school Brazilian children. Rapid weight gain was
      considered as weight gain in standard deviation score (SDS) above +0.67, +1 and
      +2 in relation to birth weight, at any time during the first 2 years of life. The
      nutritional status of the children was determined by anthropometry and electrical
      bioimpedance. Multiple linear regression analysis was used, considering fat mass
      percentage, body mass index (BMI), waist and neck circumferences as outcomes.
      RESULTS: Birth weight, rapid weight gain (assessed by different cutoff values)
      and maternal obesity were positively associated with increased fat mass
      percentage, BMI, waist and neck circumferences. Different cutoff values of rapid
      weight gain did not change the positive associations between rapid weight gain
      and fat mass percentage (>+0.67 SDS, P=0.007; >+1 SDS, P=0.007; >+2 SDS, P=0.01),
      BMI (>+0.67 SDS, P=0.002; >+1 SDS, P=0.007; >+2 SDS, P<0.001), waist
      circumference (>+0.67 SDS, P=0.002; >+1 SDS, P=0.002; >+2 SDS, P<0.001) and neck
      circumference (>+0.67 SDS, P=0.01; >+1 SDS, P=0.03; >+2 SDS, P<0.001).
      CONCLUSIONS: The use of different cutoff values for the definition of rapid
      weight gain did not interfere in the associations between birth weight and rapid
      weight gain with fat mass percentage, BMI, waist and neck circumferences.
      Children with the highest birth weight, those who undergo rapid weight gain in
      infancy and whose mothers were obese, seemed to be more at risk for
      overweight/obesity.

PMID- 24084516
TI  - Multimodality non-invasive imaging of a coronary cameral fistula.

PMID- 24084517
TI  - Visuospatial attention deficits in developmental dyslexia: evidence from visual
      and mental number line bisection tasks.
AB  - Previous research has shown that individuals with DD (developmental dyslexia)
      demonstrated a left mini neglect on visual line (VL) bisection tasks, which has
      been commonly referred to as right parietal dysfunction. However, insufficient
      reading experience characterizes dyslexia and may call into question the validity
      of this interpretation, since the VL bisection task has been found to be
      influenced by reading habits. The current study investigated whether altered
      performance of individuals with DD on bisection tasks may be attributed to
      impaired attentional mechanisms or to insufficient reading exposure. DD and
      control groups performed visual and mental number line bisection tasks, which
      have been shown to be modulated differently by reading habits. In both tasks, the
      magnitude of left bisection errors was significantly larger in the DD group
      compared with controls. This finding suggests attentional mechanisms act
      differently in dyslexia and supports evidence linking dyslexia to decreased
      function of the left hemisphere.

PMID- 24084515
TI  - Relation of the Mediterranean diet with the incidence of gestational diabetes.
AB  - BACKGROUND/OBJECTIVES: Some studies document relationships of the incidence of
      gestational diabetes mellitus (GDM) with individual components of the diet, but
      studies exploring relationships with patterns of eating are lacking. This
      observational study aimed to explore a possible relationship between the
      incidence of GDM and the Mediterranean diet (MedDiet) pattern of eating.
      SUBJECTS/METHODS: In 10 Mediterranean countries, 1076 consecutive pregnant women
      underwent a 75-g OGTT at the 24th-32nd week of gestation, interpreted both by the
      ADA_2010 and the International Association of the Diabetes and Pregnancy Study
      Groups (IADPSG)_2012 criteria. The dietary habits were assessed by a previously
      validated questionnaire and a Mediterranean Diet Index (MDI) was computed,
      reflecting the degree of adherence to the MedDiet pattern of eating: a higher MDI
      denoting better adherence. RESULTS: After adjustment for age, BMI, diabetes in
      the family, weight gain and energy intake, subjects with GDM, by either
      criterion, had lower MDI (ADA_2010, 5.8 vs 6.3, P=0.028; IADPSG_2012, 5.9 vs 6.4,
      P<0.001). Moreover, the incidence of GDM was lower in subjects with better
      adherence to the MedDiet (higher tertile of MDI distribution), 8.0% vs 12.3%,
      OR=0.618, P=0.030 by ADA_2010 and 24.3% vs 32.8%, OR=0.655, P=0.004 by
      IADPSG_2012 criteria. In subjects without GDM, MDI was negatively correlated with
      both fasting plasma glucose and AUC glucose, P<0.001 for both. CONCLUSIONS:
      Adherence to a MedDiet pattern of eating is associated with lower incidence of
      GDM and better degree of glucose tolerance, even in women without GDM. The
      possibility to use MedDiet for the prevention of GDM deserves further testing
      with intervention studies.

PMID- 24084518
TI  - Keeping the data flowing.

PMID- 24084519
TI  - Patient entrance surface dose measurements using XR-QA2 Gafchromic films during
      micturating cystourethrography procedures.
AB  - The aim of this study was to test the feasibility of using Gafchromic XR-QA2
      films in the measurements of patient entrance surface dose (ESD) during the
      micturating cystourethrogram (MCUG) examination in paediatric patients.
      Radiochromic films were used to map the entrance dose and to identify the
      location of peak surface dose (PSD). Direct in vivo measurements of entrance dose
      were conducted by placing a radiochromic film between the patient and the
      examination table. The measured ESD values for the commonly performed MCUG
      fluoroscopic examinations at the authors' institution was in the range of 1.2-7.8
      mGy and the PSD in the range of 1.2-8.5 mGy per MCUG procedure for patients with
      age ranging from 1 to 12 y old. Gafchromic films (XR-QA2) were found to be an
      efficient and practical dosimetry method that can be easily used to measure
      clinical patient entrance doses during fluoroscopically guided procedures and
      potentially in other diagnostic investigations. 

PMID- 24084520
TI  - Naturally occurring radioactive materials (NORM) in ashes from a fuel-oil power
      plant in Cienfuegos, Cuba, and the associated radiation hazards.
AB  - The radioactivity of NORM was measured in ashes collected from a fuel-oil power
      plant in Cienfuegos, Cuba, using an HPGe gamma-ray spectrometer. The (226)Ra,
      (210)Pb, (40)K, (232)Th and (238)U activity concentrations reached 240, 77, 59,
      70 and 15 Bq kg(-1), respectively. The potential radiological hazard of these
      residuals was assessed. The radium equivalent activities of the samples varied
      from 54 to 345 Bq kg(-1). The gamma index was calculated to be lower than that of
      the reference values, and the gamma absorbed dose rate was higher than the
      average reported for the earth's crust; however, the assessed annual effective
      dose was slightly lower than the annual effective dose limit for public, i.e. 1
      mSv. Therefore, these bottom ashes were not dramatically enriched with
      radionuclides and may be used as an additive for building materials without
      restrictions from a radiological protection point of view. 

PMID- 24084521
TI  - Aircrew radiation dose estimates during recent solar particle events and the
      effect of particle anisotropy.
AB  - A model was developed using a Monte-Carlo radiation transport code, MCNPX, to
      estimate the additional radiation exposure to aircrew members during solar
      particle events. The model transports an extrapolated particle spectrum based on
      satellite measurements through the atmosphere to aircraft altitudes. This code
      produces the estimated flux at a specific altitude where radiation dose
      conversion coefficients are applied to convert the particle flux into effective
      and ambient dose-equivalent rates. A cut-off rigidity model accounts for the
      shielding effects of the Earth's magnetic field. Comparisons were made between
      the model predictions and actual flight measurements taken with various types of
      instruments used to measure the mixed radiation field during ground level
      enhancements (GLEs) 60 and 65. An anisotropy analysis that uses neutron monitor
      responses and the pitch angle distribution of energetic solar particles was used
      to identify particle anisotropy for a solar event in December 2006. In
      anticipation of future commercial use, a computer code has been developed to
      implement the radiation dose assessment model for routine analysis. 

PMID- 24084522
TI  - Diversity of potassium channels in human umbilical artery smooth muscle cells: a
      review of their roles in human umbilical artery contraction.
AB  - Through their control of cell membrane potential, potassium (K(+)) channels are
      among the best known regulators of vascular tone. This article discusses the
      expression and function of K(+) channels in human umbilical artery smooth muscle
      cells (HUASMCs). We review the bibliographic reports and also present single
      channel data recorded in freshly isolated cells. Electrophysiological properties
      of big conductance, voltage- and Ca(2+)-sensitive K(+) channel and voltage
      dependent K(+) channels are clearly established in this vessel, where they are
      involved in contractile state regulation. Their role in the maintenance of
      membrane potential is an important control mechanism in the determination of the
      vessel diameter. Additionally, small conductance Ca(2+)-sensitive K(+) channels,
      2-pore domains K(+) channels and inward rectifier K(+) channels also appear to be
      present in HUASMCs, while intermediate conductance Ca(2+)-sensitive K(+) channels
      and ATP-sensitive K(+) channels could not be identified. In both cases,
      additional investigation is necessary to reach conclusive evidence of their
      expression and/or functional role in HUASMCs. Finally, we discuss the role of
      K(+) channels in pregnancy-related pathologies like gestational diabetes and
      preeclampsia. 

PMID- 24084523
TI  - Effect of prenatal hypoxia in transgenic mouse models of preeclampsia and fetal
      growth restriction.
AB  - Mice lacking endothelial nitric oxide synthase (eNOS(-)(/-)) or catechol-O-methyl
      transferase (COMT(-/-)) exhibit a preeclampsia-like phenotype and fetal growth
      restriction. We hypothesized that a hypoxic insult would result in a more severe
      phenotype. Pregnant eNOS(-/-), COMT(-/-) and control (C57BL/6J) mice were
      randomized to hypoxic (10.5% O(2)) or normal conditions (20.9% O(2)) from
      gestational day 10.5 to 18.5. Hypoxia increased the blood pressure in all
      genotypes and proteinuria in C57BL/6J and eNOS(-/-) mice. Fetal survival was
      significantly reduced following hypoxia, particularly in eNOS(-/-) mice. Birth
      weight was decreased in both C57BL/6J and COMT(-/-) mice. Placentas from COMT(-/
      ) mice demonstrated increased peroxynitrite. Despite similar hypoxia-induced
      effects on maternal blood pressure and proteinuria, eNOS(-/-) embryos have a
      decreased tolerance to hypoxia. Compared to C57BL/6J, COMT(-/-) mice exhibited
      less severe changes in proteinuria and fetal growth when exposed to prenatal
      hypoxia. This relative resistance to prenatal hypoxia was associated with a
      significant increase in placental levels of peroxynitrite.

PMID- 24084525
TI  - Local-area age structure and population composition: implications for elderly
      health in Japan.
AB  - OBJECTIVE: This study examines relationships between local-area age structure and
      health at older ages. METHOD: We estimate random intercept models for two
      disability measures using four waves of data from a national panel study of 3,580
      Japanese older adults. RESULTS: Elderly living in relatively older areas reported
      more difficulties with activities of daily living compared with those living in
      an "average" age structure. Controlling for individual characteristics and time
      did little to change this relationship; while a similar relationship between
      older age structure and functional limitations emerged. DISCUSSION: Residents of
      relatively older areas tended to have lower socioeconomic status, but this
      "disadvantage" was offset by their higher rates of employment and marriage. These
      compositional differences highlight the role of local-area age structure in
      identifying and understanding elderly health variation between places.

PMID- 24084524
TI  - Plant as a plenteous reserve of lectin.
AB  - Lectins are clusters of glycoproteins of nonimmune foundation that combine
      specifically and reversibly to carbohydrates, mainly the sugar moiety of
      glycoconjugates, resulting in cell agglutination and precipitation of
      glycoconjugates. They are universally distributed in nature, being established in
      plants, fungi, viruses, bacteria, crustacea, insects, and animals, but
      leguminacae plants are rich source of lectins. The present review reveals the
      structure, biological properties, and application of plant lectins.

PMID- 24084526
TI  - Longitudinal differences in cognitive functioning among older adults with and
      without heart failure.
AB  - OBJECTIVE: Secondary data analyses were conducted to examine cognitive function
      and longitudinal cognitive decline among older adults with and without heart
      failure (HF). METHOD: Data from the Advanced Cognitive Training for Independent
      and Vital Elderly study were used to compare baseline (N = 2,790) and
      longitudinal (n = 692) changes in memory, reasoning, and speed of processing
      performance among participants (M age = 73.61, SD = 5.89) who self-reported HF at
      baseline, developed HF over time, or never reported HF. RESULTS: At baseline,
      there were differences in memory and speed of processing with participants who
      never reported HF performing better than those who reported developing HF over
      time, and those who reported HF at baseline performing the worst (ps < .05).
      Longitudinally, participants with self-reported HF at baseline showed declines in
      reasoning over time. DISCUSSION: The results indicate that cognitive difficulties
      in memory and speed may occur prior to a HF diagnosis, while those with HF may
      experience steeper declines in reasoning as measured by word series test.

PMID- 24084527
TI  - Medical treatment of ectopic pregnancy: is there something new?

PMID- 24084528
TI  - Maternal mortality: time for national action.

PMID- 24084529
TI  - Effects of gefitinib, an epidermal growth factor receptor inhibitor, on human
      placental cell growth.
AB  - OBJECTIVE: Placenta has the highest expression of epidermal growth factor (EGF)
      receptor of all tissues, a cell signaling pathway promoting survival and growth.
      Therefore, EGF receptor inhibition could potentially treat ectopic pregnancy. We
      undertook preclinical studies to examine whether gefitinib (orally available EGF
      receptor inhibitor) with or without methotrexate inhibits placental cell growth.
      METHODS: Gefitinib and methotrexate were added to placental cells and their
      ability inhibit cell growth, block EGF receptor signaling, and induce apoptosis
      (programmed cell death) was examined. They were also administered to two animal
      mouse models to examine their effects on placental tissue in vivo. RESULTS:
      Epidermal growth factor receptor was highly expressed in placental tissue from
      ectopic pregnancies. Combining gefitinib with methotrexate potently inhibited
      growth of placental cells, including placental cell lines (JEG3, BeWo cells) and
      cells isolated from first-trimester placenta. These drugs were additive in
      blocking EGF receptor signaling and inducing apoptosis. Gefitinib and
      methotrexate administered together were more potent in decreasing the volume of
      human placental cells xenografted subcutaneously onto mice compared with either
      alone. By day 19 after xenografting, mean (+/- standard error of the mean),
      xenograft volumes were: 821 (+/- 68) mm after gefitinib treatment, 901 (+/- 204)
      mm after methotrexate treatment, and 345 (+/-137) mm after both drugs were given
      (P<.01 for both comparisons of single therapy compared with combination therapy).
      Combining these agents doubled rates of fetal resorption in pregnant mice
      compared with each drug alone. CONCLUSION: Combining gefitinib with methotrexate
      potently inhibits placental cell growth in vitro and in mouse models. The
      combination may have potential in treating ectopic pregnancies.

PMID- 24084530
TI  - Combination gefitinib and methotrexate compared with methotrexate alone to treat
      ectopic pregnancy.
AB  - OBJECTIVE: To determine the safety, tolerability, and efficacy of combination
      gefitinib and methotrexate to treat ectopic pregnancy. METHODS: We performed a
      phase I, single-arm (nonrandomized), open-label study. Twelve women with ectopic
      pregnancies were administered methotrexate (50 mg/m, intramuscular) and 250 mg
      oral gefitinib in a dose-escalation protocol: one dose (day 1) n=3; three doses
      (days 1-3) n=3; seven doses (days 1-7) n=6. Efficacy was examined by comparing
      human chorionic gonadotrophin (hCG) decline and time to resolution with historic
      controls administered methotrexate only. RESULTS: Common side effects were
      transient acneiform rash in 67% (8/12) and diarrhea in 42% (5/12) of
      participants. There was no clinical or biochemical evidence of serious pulmonary,
      renal, hepatic, or hematologic toxicity. Of six participants with a pretreatment
      serum hCG level between 1,000 and 3,000 international units/L, hCG levels
      declined significantly faster than in the control group. Median serum hCG levels
      by day 7 after treatment were less than one fifth of levels observed among 71
      historic controls treated with methotrexate alone (median [interquartile range]
      hCG in participants 261 [55-1,445] international units/L compared with controls
      1,426 [940-2,573]; P=.008). Median time for the ectopic pregnancies to resolve
      with combination therapy was 34% shorter compared with methotrexate alone (21
      days compared with 32 days; P=.018). CONCLUSION: Combination gefitinib and
      methotrexate has potential as a treatment for ectopic pregnancy but is commonly
      associated with minor side effects such as transient rash and diarrhea. The
      treatment requires validation of safety and efficacy in a larger trial. CLINICAL
      TRIAL REGISTRATION: Australian New Zealand Clinical Trials Registry,
      www.anzctr.org, AC'TRN12610000684022. LEVEL OF EVIDENCE: : II.

PMID- 24084531
TI  - Ten years of confidential inquiries into maternal deaths in France, 1998-2007.
AB  - OBJECTIVE: To assess trends in the maternal mortality ratio over a 10-year period
      in France and the causes, risk factors, quality of care, and avoidability of
      maternal deaths. METHODS: Maternal deaths up to 1 year after the end of the
      pregnancy from 1998 to 2007 were identified and studied through the French
      Confidential Enquiry Into Maternal Deaths system. Time trends were analyzed by
      comparing the two 5-year periods for maternal mortality ratios, both overall and
      by women's characteristics, causes of death, existence of suboptimal care, and
      avoidability. RESULTS: For the 10-year period, 660 maternal deaths were
      identified. The maternal mortality ratio was similar in the two 5-year periods,
      8.8 per 100,000 live births (95% confidence interval [CI] 7.8-9.8) for 1998-2002
      and 8.4 per 100,000 live births (95% CI 7.6-9.4) for 2003-2007. The distributions
      of maternal age, nationality, and of causes of death did not change. Overall,
      hemorrhage was the leading cause of death, responsible for 18% of maternal
      deaths, followed by amniotic fluid embolism, thromboembolism, hypertensive
      disorders, and cardiovascular conditions, each of which contributed to 10-12% of
      deaths. Suboptimal care decreased from 70% in 1998-2002 to 60% in 2003-2007
      (P<.03). Half of all deaths were considered avoidable and this proportion did not
      change. The most frequent contributory factor was inadequate management.
      CONCLUSION: The ratio and profile of maternal mortality in France remained
      unchanged from 1998 to 2007. Half of all maternal deaths are still considered
      avoidable, which indicates that improvement remains possible. LEVEL OF EVIDENCE:
      : III.

PMID- 24084532
TI  - Elective induction of labor at term compared with expectant management: maternal
      and neonatal outcomes.
AB  - OBJECTIVE: To test the association of elective induction of labor at term
      compared with expectant management and maternal and neonatal outcomes. METHODS:
      This was a retrospective cohort study of all deliveries without prior cesarean
      delivery in California in 2006 using linked hospital discharge and vital
      statistics data. We compared elective induction at each term gestational age (37
      40 weeks) as defined by The Joint Commission with expectant management in vertex,
      nonanomalous, singleton deliveries. We used multivariable logistic regression to
      test the association of elective induction and cesarean delivery, operative
      vaginal delivery, maternal third- or fourth-degree lacerations, perinatal death,
      neonatal intensive care unit admission, respiratory distress, shoulder dystocia,
      hyperbilirubinemia, and macrosomia (birth weight greater than 4,000 g) at each
      gestational week, stratified by parity. RESULTS: The cesarean delivery rate was
      16%, perinatal mortality was 0.2%, and neonatal intensive care unit admission was
      6.2% (N=362,154). The odds of cesarean delivery were lower among women with
      elective induction compared with expectant management across all gestational ages
      and parity (37 weeks [odds ratio (OR) 0.44, 95% confidence interval (CI) 0.34
      0.57], 38 weeks [OR 0.43, 95% CI 0.38-0.50], 39 weeks [OR 0.46, 95% CI 0.41
      0.52], 40 weeks [OR 0.57, CI 0.50-0.65]). Elective induction was not associated
      with increased odds of severe lacerations, operative vaginal delivery, perinatal
      death, neonatal intensive care unit admission, respiratory distress, shoulder
      dystocia, or macrosomia at any term gestational age. Elective induction was
      associated with increased odds of hyperbilirubinemia at 37 and 38 weeks of
      gestation and shoulder dystocia at 39 weeks of gestation. CONCLUSION: Elective
      induction of labor is associated with decreased odds of cesarean delivery when
      compared with expectant management. LEVEL OF EVIDENCE: : II.

PMID- 24084533
TI  - Three-year outcomes of vaginal mesh for prolapse: a randomized controlled trial.
AB  - OBJECTIVE: To present the 3-year outcomes of a double-blind, multicenter,
      randomized trial comparing vaginal prolapse repair with and without mesh.
      METHODS: This was a planned final analysis of women with Pelvic Organ Prolapse
      Quantification (POP-Q) stage 2-4 prolapse randomized to traditional vaginal
      prolapse surgery without mesh and vaginal colpopexy repair with mesh. We
      evaluated anatomic, symptomatic, and combined cure rates for those with at least
      3-year validated quality-of-life questionnaires and 2- or 3-year postoperative
      blinded POP-Q examination. Participants undergoing reoperation for recurrent
      prolapse were removed for anatomic and subjective outcomes analysis and
      considered failures for combined outcomes analysis. RESULTS: Sixty-five women
      were enrolled (33 mesh, 32 no mesh) before the study was prematurely halted as a
      result of a 15.6% mesh exposure rate. At 3 years, 51 of 65 (78%) had quality-of
      life questionnaires (25 mesh, 26 no mesh) and 41 (63%) had examinations. Three
      participants died, three required reoperation for recurrent prolapse (all in mesh
      group), and eight were lost to follow-up. No differences were observed between
      groups at 3 years for prolapse stage or individual prolapse points. Stage
      improved for each group (90% and 86%) from baseline to 3 years (P<.01).
      Symptomatic improvement was observed with no differences in scores between
      groups. Cure rates did not differ between groups using a variety of definitions,
      and anatomic cure was lowest for the anterior compartment. CONCLUSION: There was
      no difference in 3-year cure rates when comparing patients undergoing traditional
      vaginal prolapse surgery without mesh with those undergoing vaginal colpopexy
      repair with mesh. CLINICAL TRIAL REGISTRATION: Clinicaltrials.gov,
      www.clinicaltrials.gov, NCT00475540. LEVEL OF EVIDENCE: : I.

PMID- 24084534
TI  - Comparison of robotic and laparoscopic hysterectomy for benign gynecologic
      disease.
AB  - OBJECTIVE: Use of robotically assisted hysterectomy for benign gynecologic
      conditions is increasing. Using the most recent, available nationwide data, we
      examined clinical outcomes, safety, and cost of robotic compared with
      laparoscopic hysterectomy. METHODS: Women undergoing robotic or laparoscopic
      hysterectomy for benign disease were identified from the United States 2009 and
      2010 Nationwide Inpatient Sample. Propensity scores derived from a logistic
      regression model were used to assemble matched cohorts of patients undergoing
      robotic and laparoscopic hysterectomy. Differences in in-hospital complications,
      hospital length of stay, and hospital charges were assessed between the matched
      groups. RESULTS: Of the 804,551 hysterectomies for benign conditions performed in
      2009 and 2010, 20.6% were laparoscopic and 5.1% robotically assisted. Among
      minimally invasive hysterectomies, the use of robotic hysterectomy increased from
      9.5% to 13.6% (P=.002). In a propensity-matched analysis, the overall
      complication rates were similar between robotic and laparoscopic hysterectomy
      (8.80% compared with 8.85%, relative risk 0.99, 95% confidence interval [CI] 0.89
      1.09, P=.910). There was a lower incidence of blood transfusions in robotic cases
      (2.1% compared with 3.1%; P<.001), but patients undergoing robotic hysterectomy
      were more likely to experience postoperative pneumonia (relative risk 2.2, 95% CI
      1.24-3.78, P=.005). The median cost of hospital care was $9,788 (interquartile
      range $7,105-12,780) for robotic hysterectomy and $7,299 (interquartile range
      $5,650-9,583) for laparoscopic hysterectomy (P<.001). Hospital costs were on
      average $2,489 (95% CI $2,313-2,664) higher for patients undergoing robotic
      hysterectomy. CONCLUSION: The use of robotic hysterectomy has increased.
      Perioperative outcomes are similar between laparoscopic and robotic hysterectomy,
      but robotic cases cost substantially more. LEVEL OF EVIDENCE: : II.

PMID- 24084535
TI  - Histopathologic characteristics of menopausal vestibulodynia.
AB  - OBJECTIVE: To assess whether premenopausal and postmenopausal vestibulodynia have
      different histologic features. METHODS: We conducted a retrospective analysis of
      vestibulectomy specimens from 21 women with postmenopausal vestibulodynia and
      compared them with 88 premenopausal patients (42 primary, 46 secondary). Women
      with primary vestibulodynia experienced pain at first introital touch and women
      with secondary vestibulodynia experienced pain after an interval of painless
      intercourse. Clinical records established the type of vestibulodynia, duration of
      symptoms, and hormone status. Tissues were stained for inflammation, nerves, mast
      cells, estrogen receptor alpha, and progesterone receptor. Histologic findings in
      the postmenopausal patients were compared with primary and secondary
      premenopausal patients using proportional odds logistic regression and analysis
      of variance. RESULTS: Seventy-one percent (15/21) of postmenopausal women
      reported vestibular dyspareunia related to a drop in estrogen either with
      menopause (13/21) or previously, postpartum (2/21). Eighty-six percent (18/21) of
      postmenopausal patients were using local or systemic estrogen but pain persisted.
      Compared with premenopausal primary and secondary vestibular biopsies,
      postmenopausal tissues had more lymphocytes (unadjusted odds ratio [OR] 9.0, 95%
      confidence interval [CI] 2.8-33.3; adjusted OR for parity and duration of
      symptoms 9.1, 95% CI 2.6-31.9; unadjusted OR 6.2, 95% CI 1.9-20.0; adjusted OR
      6.6, 95% CI 2.0-21.9, respectively) and mast cells (mean 36 compared with 28 and
      36 compared with 26, respectively). There was significantly less neural
      hyperplasia and progesterone receptor expression in postmenopausal biopsies
      compared with primary cases but less progesterone receptor and similar neural
      hyperplasia compared with premenopausal secondary cases. Estrogen receptor alpha
      did not vary among groups. CONCLUSION: Premenopausal and postmenopausal
      vestibulodynia share histologic features of neurogenic inflammation but differ
      strikingly in degree. When estrogen supplement does not alleviate symptoms of
      postmenopausal dyspareunia, vestibulodynia should be considered. LEVEL OF
      EVIDENCE: : II.

PMID- 24084536
TI  - Clinical and microbiological characteristics of Bartholin gland abscesses.
AB  - OBJECTIVE: To examine the clinical course and causative microorganisms of
      Bartholin gland abscesses. METHODS: This was a retrospective study of all
      patients treated for Bartholin gland abscesses between the years 2006 and 2011 at
      the Soroka University Medical Center, a regional medical center in southern
      Israel. RESULTS: During the study period, 219 women were admitted as a result of
      an abscess of the Bartholin gland, 63% of which were primary abscesses and 37%
      recurrent abscesses (occurrence of a second clinical event). Pus cultures were
      positive in 126 (61.8%) of cases. Escherichia coli was the single most frequent
      pathogen found (43.7%) and 10 cases (7.9%) were polymicrobial. Culture-positive
      cases were significantly associated with fever (25% compared with 9.3%; P=.043),
      leukocytosis (50.4% compared with 33.8%; P=.027), and neutrophilia (17.9%
      compared with 5.9%; P=.021). The odds ratio of having any of these with a
      positive culture was 2.4 (95% confidence interval 1.3-4.3; P=.003). In the
      recurrent group, 81% recurred ipsilaterally and the mean time for recurrence was
      32 +/- 50 months. Infection with E coli was significantly more common in
      recurrent infection compared with primary infections (56.8% compared with 37%;
      P=.033). Three cases of resistance to most beta-lactam antimicrobials (extended
      spectrum beta-lactamase-producing [E coli] strains) were identified. CONCLUSION:
      A substantial proportion of patients with Bartholin gland abscess are culture
      positive with E coli being the single most common pathogen. Microbiological
      findings coupled with their clinical correlates are important parameters in the
      management of patients with a Bartholin gland abscess and in the selection of
      empirical antimicrobial treatment during the primary diagnosis. LEVEL OF
      EVIDENCE: : III.

PMID- 24084537
TI  - Cardiovascular risk associated with the use of an etonogestrel-containing vaginal
      ring.
AB  - OBJECTIVE: To compare the risks of short-term and long-term use of an
      etonogestrel-containing and ethinylestradiol-containing vaginal ring and combined
      oral contraceptive pills (OCPs) in a routine clinical study population. METHODS:
      This was a prospective, controlled, noninterventional cohort study performed in
      the United States and five European countries with the following two cohorts: new
      users of the vaginal ring and new users of combined OCPs (starters, switchers, or
      restarters). The study population included 33,295 users of the vaginal ring or
      combined OCPs recruited by 1,661 study centers. Follow-up of study participants
      occurred for 2 to 4 years. Main clinical outcomes of interest were cardiovascular
      outcomes, particularly venous and arterial thromboembolism. These outcomes were
      validated by attending physicians and further adjudicated by an independent
      board. Comprehensive follow-up ensured low loss to follow-up. Statistical
      analyses were based on Cox regression models. Primary statistical variable was
      the venous thromboembolic hazard ratio (HR) for the vaginal ring compared with
      combined OCPs. RESULTS: Study participants were followed-up for 66,489 woman
      years. Loss to follow-up was 2.9%. The venous thromboembolism incidence rates for
      the vaginal ring users and combined OCPs users were 8.3 and 9.2 per 10,000 woman
      years, respectively. Cox regression analysis yielded crude and adjusted HRs for
      the vaginal ring users compared with combined OCPs users of 0.9 and 0.8 for
      venous thromboembolism (95% confidence intervals [CIs] 0.5-1.6 and 0.5-1.5) and
      0.8 and 0.7 (95% CIs 0.2-2.5 and 0.2-2.3) for arterial thromboembolism,
      respectively. CONCLUSION: Vaginal ring use and combined OCP use were associated
      with a similar venous and arterial thromboembolic risk during routine clinical
      use. LEVEL OF EVIDENCE: : II.

PMID- 24084538
TI  - Contraception and fertility awareness among women with solid organ transplants.
AB  - OBJECTIVE: To assess the contraception and fertility counseling provided to women
      with solid organ transplants. METHODS: A telephone survey of 309 women aged 19-49
      years who had received a solid organ transplant at the University of Nebraska
      Medical Center was performed. Of the 309 eligible women, 183 responded. Patients
      were asked 19 questions regarding pretransplant and posttransplant fertility
      awareness and contraception counseling. Data were summarized using descriptive
      statistics. RESULTS: Patients had undergone a variety of solid organ
      transplantations: 40% kidney (n=73); 32% liver (n=59); 6% pancreas (n=11); 5%
      heart (n=9); 3% intestine (n=5); and 14% multiple organs (n=26). Before their
      transplantations, 79 women (44%) reported they were not aware that a woman could
      become pregnant after transplantation. Only 66 women aged 13 and older at the
      time of transplantation reported that a health care provider discussed
      contraception before transplantation. Approximately half of women surveyed were
      using a method of contraception. Oral contraceptive pills were the most commonly
      recommended method. Twenty-two of the 31 pregnancies after organ transplantation
      were planned, which is higher than that of the general population. CONCLUSION:
      Few women with transplants are educated regarding the effect of organ
      transplantation on fertility and are not routinely counseled about contraception
      or the potential for posttransplant pregnancy. Health care providers should
      incorporate contraceptive and fertility counseling as part of routine care for
      women with solid organ transplants. LEVEL OF EVIDENCE: : II.

PMID- 24084539
TI  - Mifepristone followed by misoprostol or oxytocin for second-trimester abortion: a
      randomized controlled trial.
AB  - OBJECTIVE: To compare two methods for induction of second-trimester abortion
      after priming the cervix with mifepristone. METHODS: This was a randomized
      prospective trial carried out between January 2009 and February 2012. The
      participants were healthy women between 14 and 24 weeks of gestation with missed
      miscarriage or need for termination of pregnancy. All participants received oral
      200 mg mifepristone and, after 36 hours, after randomization, were given either a
      high-concentration oxytocin drip (maximal dose of 150 milli-international
      units/min) for up to 36 hours or 800 micrograms misoprostol vaginally followed by
      400 micrograms oral misoprostol every 3 hours with a maximum of four oral doses.
      If expulsion of the fetus was not achieved, another 200 mg mifepristone was
      administered and another course of misoprostol was delivered as described
      previously. The primary outcome measure was success expulsion of the fetus in 36
      hours since starting on uterotonic agent. Secondary outcomes included time until
      expulsion of the fetus and rate of adverse outcomes. RESULTS: Success rates in
      the mifepristone-misoprostol and mifepristone-oxytocin arms were 100% (70/70
      patients) and 95.8% (69/72), respectively (relative risk 1.043, 95% confidence
      interval 0.99-1.10, P=.13). Time until fetal expulsion was shorter in the
      mifepristone-misoprostol arm (7.0 +/- 4.9 hours compared with 11.3 +/- 7.4 hours,
      P<.001). However, the rate of adverse effects in the misoprostol group was higher
      than in the oxytocin group. Factors associated with a shorter time until
      expulsion were missed miscarriage compared with therapeutic abortion, increased
      ultrasonographic gestational age, and increased parity. CONCLUSION: The two
      regimens studied had comparable efficacy for induction of second-trimester
      abortion; however, the mifepristone-oxytocin regimen has a longer time until
      expulsion but with fewer side effects. CLINICAL TRIAL REGISTRATION:
      ClinicalTrials.gov, www.clinicaltrials.gov, NCT00784797. LEVEL OF EVIDENCE: : I.

PMID- 24084541
TI  - Association between maternal alcohol consumption in early pregnancy and pregnancy
      outcomes.
AB  - OBJECTIVE: To investigate the association between alcohol consumption and binge
      drinking before and during early pregnancy and adverse pregnancy outcomes.
      METHODS: We used data from 5,628 nulliparous pregnant participants recruited to
      the Screening for Pregnancy Endpoints (SCOPE) study, a prospective cohort study.
      Participants were interviewed at 15 weeks of gestation and information on alcohol
      intake before pregnancy and until the time of interview was obtained using a
      standardized questionnaire. Alcohol intake was classified as occasional (1-2
      units per week), low (3-7 units per week), moderate (8-14 units per week), and
      heavy (greater than 14 units per week). Binge alcohol consumption was defined as
      consumption of 6 or more alcohol units in one session. RESULTS: Of the 5,628
      participants, 1,090 (19%) reported occasional alcohol consumption, 1,383 (25%)
      low alcohol consumption, 625 (11%) moderate alcohol consumption, and 300 (5%)
      heavy alcohol consumption. Overall, 1,905 (34%) participants reported binge
      alcohol consumption in the 3 months before pregnancy, and 1,288 (23%) of these
      participants reported binge alcohol consumption during the first 15 weeks of
      pregnancy. Participants who consumed occasional to heavy amounts of alcohol in
      early pregnancy did not have altered odds of a small-for-gestational-age neonate,
      reduced birth weight, preeclampsia, or spontaneous preterm birth. Similarly,
      those who binge drank in early pregnancy did not have altered odds of these
      adverse pregnancy outcomes. CONCLUSION: Alcohol consumption in early pregnancy
      was prevalent in this nulliparous cohort. There was no association between
      alcohol consumption before 15 weeks of gestation and small for gestational age,
      reduced birth weight, preeclampsia, or spontaneous preterm birth. LEVEL OF
      EVIDENCE: : II.

PMID- 24084540
TI  - Cost-effectiveness of preoperative imaging for appendicitis after indeterminate
      ultrasonography in the second or third trimester of pregnancy.
AB  - OBJECTIVE: To assess the cost-effectiveness of diagnostic laparoscopy, computed
      tomography (CT), and magnetic resonance imaging (MRI) after indeterminate
      ultrasonography in pregnant women with suspected appendicitis. METHODS: A
      decision-analytic model was developed to simulate appendicitis during pregnancy
      taking into consideration the health outcomes for both the pregnant women and
      developing fetuses. Strategies included diagnostic laparoscopy, CT, and MRI.
      Outcomes included positive appendectomy, negative appendectomy, maternal
      perioperative complications, preterm delivery, fetal loss, childhood cancer,
      lifetime costs, discounted life expectancy, and incremental cost-effectiveness
      ratios. RESULTS: Magnetic resonance imaging is the most cost-effective strategy,
      costing $6,767 per quality-adjusted life-year gained relative to CT, well below
      the generally accepted $50,000 per quality-adjusted life-year threshold. In a
      setting where MRI is unavailable, CT is cost-effective even when considering the
      increased risk of radiation-associated childhood cancer ($560 per quality
      adjusted life-year gained relative to diagnostic laparoscopy). Unless the
      negative appendectomy rate is less than 1%, imaging of any type is more cost
      effective than proceeding directly to diagnostic laparoscopy. CONCLUSIONS:
      Depending on imaging costs and resource availability, both CT and MRI are
      potentially cost-effective. The risk of radiation-associated childhood cancer
      from CT has little effect on population-level outcomes or cost-effectiveness but
      is a concern for individual patients. For pregnant women with suspected
      appendicitis, an extremely high level of clinical diagnostic certainty must be
      reached before proceeding to operation without preoperative imaging.

PMID- 24084543
TI  - Risk factors for classical hysterotomy by gestational age.
AB  - OBJECTIVE: To examine the likelihood of classical hysterotomy across preterm
      gestational ages and to identify factors that increase its occurrence. METHODS:
      This is a secondary analysis of a prospective observational cohort collected by
      the Maternal-Fetal Medicine Network of all women with singleton gestations who
      underwent a cesarean delivery with a known hysterotomy. Comparisons were made
      based on gestational age. Factors thought to influence hysterotomy type were
      studied, including maternal age, body mass index, parity, birth weight, small for
      gestational age (SGA) status, fetal presentation, labor preceding delivery, and
      emergent delivery. RESULTS: Approximately 36,000 women were eligible for
      analysis, of whom 34,454 (95.7%) underwent low transverse hysterotomy and 1,562
      (4.3%) underwent classical hysterotomy. The median gestational age of women
      undergoing a classical hysterotomy was 32 weeks and the incidence peaked between
      24 0/7 weeks and 25 6/7 weeks (53.2%), declining with each additional week of
      gestation thereafter (P for trend <.001). In multivariable regression, the
      likelihood of classical hysterotomy was increased with SGA (n=258; odds ratio
      [OR] 2.71; confidence interval [CI] 1.78-4.13), birth weight 1,000 g or less
      (n=467; OR 1.51; CI 1.03-2.24), and noncephalic presentation (n=783; OR 2.03; CI
      1.52-2.72). The likelihood of classical hysterotomy was decreased between 23 0/7
      and 27 6/7 weeks of gestation and after 32 weeks of gestation when labor preceded
      delivery, and increased between 28 0/7 and 31 6/7 weeks of gestation and after 32
      weeks of gestation by multiparity and previous cesarean delivery. Emergent
      delivery did not predict classical hysterotomy. CONCLUSIONS: Fifty percent of
      women at 23-26 weeks of gestation who undergo cesarean delivery have a classical
      hysterotomy, and the risk declines steadily thereafter. This likelihood is
      increased by fetal factors, especially SGA and noncephalic presentation. LEVEL OF
      EVIDENCE: : II.

PMID- 24084542
TI  - Periconceptional use of opioids and the risk of neural tube defects.
AB  - OBJECTIVE: Opioid medications are among the most effective analgesics. However,
      the consequences of opioid exposure to the developing human offspring are not
      known. We assessed whether maternal opioid use in the periconceptional period was
      associated with the risk of neural tube defects in the offspring. METHODS: We
      used data from 1998 to 2010 from the Slone Epidemiology Center Birth Defects
      Study, an ongoing case-control study. Mothers were interviewed by telephone
      within 6 months of delivery about sociodemographic factors and exposures during
      pregnancy including detailed questions on type and timing of medication use.
      Mothers of 305 offsprings with neural tube defect were compared with mothers of
      7,125 offsprings in the nonmalformed control group and 13,405 offsprings in the
      malformed control group. Periconceptional opioid use was defined as any reported
      use in the 2 months after the last menstrual period. Logistic regression models
      were used to estimate odds ratios (ORs) and 95% confidence intervals (CIs)
      adjusted for study center. RESULTS: A higher percentage of mothers of offsprings
      with neural tube defects (3.9%) reported using an opioid medication than mothers
      of offsprings in the nonmalformed control group (1.6%) and offsprings in the
      malformed control group (2.0%) with adjusted ORs of 2.2 (95% CI 1.2 -4.2) and 1.9
      (95% CI 1.0 -3.4), respectively. When offsprings were restricted to those with
      spina bifida, the adjusted ORs were 2.5 (95% CI 1.3-5.0) and 2.2 (95% CI 1.1
      4.1), respectively. CONCLUSION: A 2.2-fold increase in risk would translate to a
      neural tube defect prevalence of 5.9 per 10,000 live births among women who use
      opioids. Overall, opioid use in the periconceptional period appeared to be
      associated with a modest increased risk of neural tube defects. LEVEL OF
      EVIDENCE: : II.

PMID- 24084544
TI  - Systems factors in obstetric care: the role of daily obstetric volume.
AB  - OBJECTIVE: To evaluate whether relatively high-volume days are associated with
      measures of obstetric care in California hospitals. METHODS: This is a population
      based retrospective cohort study of linked data from birth certificates and
      antepartum and postpartum hospital discharge records for California births in
      2006. Birth asphyxia and nulliparous, term, singleton, vertex cesarean delivery
      rates were analyzed as markers of quality of obstetric care. Rates were compared
      between hospital-specific relatively high-volume days (days when the number of
      births exceeded the 75th percentile of daily volume for that hospital) and low
      volume or average-volume days. Analyses were stratified by weekend and weekday
      and overall hospital obstetric volume. Multivariable logistic regression was used
      to control for confounders. RESULTS: On weekends, relatively high-volume days
      were significantly associated with an elevated risk of asphyxia (27 out of 10,000
      compared with 17 out of 10,000; P=.013), whereas no association was present on
      weekdays (13 out of 10,000 on high-volume days and 15 out of 10,000 on low-volume
      or average-volume days; P=.182). The cesarean delivery rate among the
      nulliparous, term, singleton, vertex population was significantly lower on high
      volume weekend days (22.0% compared with 23.6% on low-volume or average-volume
      weekend days; P=.009), whereas no association was present on weekdays (27.1% on
      high-volume days and 27.6% on low-volume or average-volume days; P=.092).
      CONCLUSION: Delivery on relatively high-volume weekend days is a risk factor for
      birth asphyxia in California. High-volume weekend days also are associated with a
      lower rate of cesarean delivery in nulliparous women with singleton, vertex
      presentation pregnancies at term. LEVEL OF EVIDENCE: : II.

PMID- 24084545
TI  - Short ultrasonographic cervical length in women with low-risk obstetric history.
AB  - OBJECTIVE: To understand the relationship between cervical length and the risk of
      prematurity in parous women without a history of preterm delivery. METHODS: Data
      from 2,998 singleton pregnancies enrolled in a multicenter, observational cohort
      study were analyzed. We subgrouped the population into the following categories:
      those with history of at least one spontaneous preterm birth (n=467); nulliparous
      (n=1,237); and parous with a history of at least one term birth and no previous
      preterm birth (low-risk history group, n=1,284). The relationship between
      cervical length (measured between 22 and 24 6/7 weeks of gestation) and preterm
      birth was examined using logistic regression [corrected].Assuming a 40% risk
      reduction with the use of vaginal progesterone, we calculated the number needed
      to screen to prevent one preterm birth. RESULTS: An inverse relationship between
      cervical length and risk of preterm birth was demonstrated for each subgroup. A
      short cervix (15 mm or less) was identified in only 0.93% of the low-risk group
      participants compared with 3.4% of the previous preterm birth group participants
      and 2.1% of nulliparous women. The overall rate of preterm birth was lowest
      (10.5%) in the low-risk history group; however, the rate of preterm birth for
      these women with a short cervix was 25%. For a cervical length cutoff of 15 mm or
      less, preventing one spontaneous delivery before 34 weeks of gestation would
      require screening 167 (95% confidence interval [CI] 112-317) women with a
      previous preterm birth, 344 (95% CI 249-555) nulliparous women, and 1,075 (95% CI
      667-2,500) women at low risk. CONCLUSIONS: Although ultrasonographic short cervix
      is a risk factor for preterm birth among parous women with exclusively term
      births, the incidence of a short cervix is very low. The number needed to screen
      to prevent one preterm birth is considerably greater for women who have a low
      risk obstetric history. LEVEL OF EVIDENCE: : II.

PMID- 24084546
TI  - Association between second-trimester cervical length and primary cesarean
      delivery.
AB  - OBJECTIVE: To evaluate whether an increased ultrasonographic cervical length in
      the second trimester is associated with an increased frequency of cesarean
      delivery. METHODS: This is a retrospective cohort study of nulliparous women with
      a singleton pregnancy who underwent routine cervical length screening between 16
      and 24 weeks of gestation and labored after 34 weeks of gestation at a single
      tertiary care hospital. Women were grouped by cervical length quartile, and the
      association between cervical length quartile and cesarean delivery was determined
      in both univariable and multivariable analyses. RESULTS: For every additional
      centimeter of cervical length, the odds of cesarean delivery increased by 20.3%.
      Similarly, the frequency of cesarean delivery increased with increasing second
      trimester cervical length quartiles (17.4%, 22.3%, 21.8%, 27.7%; P<.001). This
      association persisted in multivariable analyses that included gestational age at
      delivery and induction of labor. This increased risk of cesarean delivery was
      primarily the result of women with arrest disorders in the first stage of labor
      (P<.001). CONCLUSION: Increased second-trimester cervical length quartile is
      associated with an increased frequency of primary cesarean delivery in
      nulliparous women. LEVEL OF EVIDENCE: : II.

PMID- 24084547
TI  - Antecedents of cerebral palsy and perinatal death in term and late preterm
      singletons.
AB  - OBJECTIVE: To examine the antecedents of cerebral palsy and of perinatal death in
      singletons born at or after 35 weeks of gestation. METHODS: From a total
      population of singletons born at or after 35 weeks of gestation, we identified
      494 with cerebral palsy and 508 neonates in a matched control group, 100 neonatal
      deaths, and 73 intrapartum stillbirths (all deaths in selected birth years).
      Neonatal death and cerebral palsy were categorized as without encephalopathy,
      after neonatal encephalopathy, or after neonatal encephalopathy considered
      hypoxic-ischemic. We examined the contribution of potentially asphyxial birth
      events, inflammation, fetal growth restriction, and birth defects recognized by
      age 6 years to each of these outcomes and to intrapartum stillbirths. RESULTS:
      The odds of total cerebral palsy after potentially asphyxial birth events or
      inflammation were modestly increased (odds ratio [OR] 1.9, 95% confidence
      interval [CI] 1.1-3.2 and OR 2.2, 95% CI 1.0-4.2, respectively). However,
      potentially asphyxial birth events occurred in 34% of intrapartum stillbirths and
      21.6% of cerebral palsy after hypoxic-ischemic encephalopathy. Inflammatory
      markers occurred in 13.9% and 11.9% of these outcomes, respectively. Growth
      restriction contributed significantly to all poor outcome groups. Birth defects
      were recognized in 5.5% of neonates in the control group compared with 60% of
      neonatal deaths and more than half of cases of cerebral palsy without hypoxic
      ischemic encephalopathy. In children with cerebral palsy, a potentially asphyxial
      birth event, inflammation, or both were experienced by 12.6%, whereas growth
      restriction, a birth defect, or both were experienced by 48.6% (P<.001).
      CONCLUSION: Fetal growth restriction and birth defects recognized by age 6 years
      were more substantial contributors to cerebral palsy and neonatal death than
      potentially asphyxial birth events and inflammation. LEVEL OF EVIDENCE: : II.

PMID- 24084548
TI  - Subcuticular suture compared with staples for skin closure after cesarean
      delivery: a randomized controlled trial.
AB  - OBJECTIVE: To compare subcuticular sutures with staples for skin closure after
      cesarean delivery in a randomized trial in which each woman was her own control.
      METHODS: Women undergoing cesarean delivery (primary, n=32; repeat, n=31) were
      randomized to side distribution of skin closure methods with one side of the skin
      incision closed with staples and the other side closed with subcuticular suture.
      The primary outcome was the overall preferred side of the scar 6 months
      postoperatively. Additional outcomes were women's preferred method of closure and
      cosmetically preferred side of the scar, difference in objective cosmetic scores
      (assessed by two plastic surgeons), and pain between the two sides of the scar
      and infection rate. RESULTS: Significantly more women preferred the stapled side,
      both overall (odds ratio [OR] 2.55; 95% confidence interval [CI] 1.18-5.52) and
      cosmetically (OR 2.67; 95% CI 1.24-5.74), and reported staples as their preferred
      technique (OR 2.00; 95% CI 1.10-3.64). There were no significant differences in
      pain scores at any time. One plastic surgeon preferred the stapled side (OR 2.8;
      95% CI 1.01-7.78) and scored it significantly higher on a cosmetic visual analog
      scale (P=.031); the other found no significant difference. There were four (6.8%)
      cases of infection-three on the sutured side and one bilateral. CONCLUSION:
      Staples were preferred to subcuticular suture for skin closure by women after
      cesarean delivery. CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov;
      www.clinicaltrials.gov; NCT01217567. LEVEL OF EVIDENCE: : I.

PMID- 24084550
TI  - What is new in intrauterine devices? Best articles from the past year.
AB  - This month, we focus on current research about intrauterine devices. Dr. Hurd
      discusses four recent publications, and each is concluded with a "bottom line"
      that is the take-home message. The complete reference for each can be found in on
      this page, along with direct links to the abstracts. 

PMID- 24084551
TI  - Leveraging the Affordable Care Act to improve the health of mothers and newborns.

PMID- 24084549
TI  - Prophylaxis and treatment of anthrax in pregnant women.
AB  - OBJECTIVE: To review the safety and pharmacokinetics of antimicrobials
      recommended for anthrax postexposure prophylaxis and treatment in pregnant women.
      DATA SOURCES: Articles were identified in the PubMed database from inception
      through December 2012 by searching the keywords (["pregnancy]" and [generic
      antibiotic drug name]). Additionally, we searched clinicaltrials.gov and
      conducted hand searches of references from REPROTOX, TERIS, review articles, and
      Briggs' Drugs in Pregnancy and Lactation. METHODS OF STUDY SELECTION: Articles
      included in the review contain primary data related to the safety and
      pharmacokinetics among pregnant women of 14 antimicrobials recommended for
      anthrax postexposure prophylaxis and treatment (amoxicillin, ampicillin,
      chloramphenicol, clindamycin, ciprofloxacin, doripenem, doxycycline,
      levofloxacin, linezolid, meropenem, moxifloxacin, penicillin, rifampin, and
      vancomycin). TABULATION, INTEGRATION, AND RESULTS: The PubMed search identified
      3,850 articles for review. Reference hand searching yielded nine additional
      articles. In total, 112 articles met the inclusion criteria. CONCLUSIONS:
      Overall, safety and pharmacokinetic information is limited for these
      antimicrobials. Although small increases in risks for certain anomalies have been
      observed with some antimicrobials recommended for prophylaxis and treatment of
      anthrax, the absolute risk of these antimicrobials appears low. Given the high
      morbidity and mortality associated with anthrax, antimicrobials should be dosed
      appropriately to ensure that antibiotic levels can be achieved and sustained.
      Dosing adjustments may be necessary for the beta-lactam antimicrobials and the
      fluoroquinolones to achieve therapeutic levels in pregnant women. Data indicate
      that the beta-lactam antimicrobials, the fluoroquinolones, and, to a lesser
      extent, clindamycin enter the fetal compartment, an important consideration in
      the treatment of anthrax, because these antimicrobials may provide additional
      fetal benefit in the second and third trimesters of pregnancy.

PMID- 24084552
TI  - Value of urodynamics before stress urinary incontinence surgery: a randomized
      controlled trial.

PMID- 24084553
TI  - In reply.

PMID- 24084554
TI  - Trends in hospital volume and patterns of referral for women with gynecologic
      cancers: adherence to treatment guidelines for ovarian cancer as a measure of
      quality care.

PMID- 24084555
TI  - In reply.

PMID- 24084556
TI  - In reply.

PMID- 24084557
TI  - Health information technology.

PMID- 24084558
TI  - In reply.

PMID- 24084559
TI  - Tubal factor infertility and perinatal risk after assisted reproductive
      technology.

PMID- 24084560
TI  - Tubal factor infertility and perinatal risk after assisted reproductive
      technology.

PMID- 24084561
TI  - In reply.

PMID- 24084566
TI  - Practice bulletins No. 139: premature rupture of membranes.
AB  - Preterm delivery occurs in approximately 12% of all births in the United States
      and is a major factor that contributes to perinatal morbidity and mortality ().
      Preterm premature rupture of membranes (PROM) complicates approximately 3% of all
      pregnancies in the United States (). The optimal approach to clinical assessment
      and treatment of women with term and preterm PROM remains controversial.
      Management hinges on knowledge of gestational age and evaluation of the relative
      risks of delivery versus the risks of expectant management (eg, infection,
      abruptio placentae, and umbilical cord accident). The purpose of this document is
      to review the current understanding of this condition and to provide management
      guidelines that have been validated by appropriately conducted outcome-based
      research when available. Additional guidelines on the basis of consensus and
      expert opinion also are presented. 

PMID- 24084567
TI  - Exposure to toxic environmental agents.
AB  - : Reducing exposure to toxic environmental agents is a critical area of
      intervention for obstetricians, gynecologists, and other reproductive health care
      professionals. Patient exposure to toxic environmental chemicals and other
      stressors is ubiquitous, and preconception and prenatal exposure to toxic
      environmental agents can have a profound and lasting effect on reproductive
      health across the life course. Prenatal exposure to certain chemicals has been
      documented to increase the risk of cancer in childhood; adult male exposure to
      pesticides is linked to altered semen quality, sterility, and prostate cancer;
      and postnatal exposure to some pesticides can interfere with all developmental
      stages of reproductive function in adult females, including puberty, menstruation
      and ovulation, fertility and fecundity, and menopause. Many environmental factors
      harmful to reproductive health disproportionately affect vulnerable and
      underserved populations, which leaves some populations, including underserved
      women, more vulnerable to adverse reproductive health effects than other
      populations. The evidence that links exposure to toxic environmental agents and
      adverse reproductive and developmental health outcomes is sufficiently robust,
      and the American College of Obstetricians and Gynecologists and the American
      Society for Reproductive Medicine join leading scientists and other clinical
      practitioners in calling for timely action to identify and reduce exposure to
      toxic environmental agents while addressing the consequences of such exposure. 

PMID- 24084568
TI  - Committee opinion No. 576: health care for homeless women.
AB  - : Homelessness continues to be a significant problem in the United States. Women
      and families represent the fastest growing segment of the homeless population.
      Health care for these women is a challenge but an important issue that needs to
      be addressed. Homeless women are at higher risk of injury and illness and are
      less likely to obtain needed health care than women who are not homeless. It is
      essential to undertake efforts to prevent homelessness, to expand community-based
      services for the homeless, and to provide adequate health care for this
      underserved population. Health care providers can help address the needs of
      homeless individuals by identifying their own patients who may be homeless or at
      risk of becoming homeless, educating these patients about available resources in
      the community, treating their health problems, and offering preventive care. 

PMID- 24084569
TI  - Phase diagram and piezoelectric response of (Ba1-xCax)(Zr0.1Ti0.9)O3 solid
      solution.
AB  - We report the phase diagram of (Ba1-xCax)(Zr0.1Ti0.9)O3 solid solution. It is
      found that substitution of smaller Ca ions for Ba ions can slightly increase the
      cubic-tetragonal (T) para-ferroelectric phase transition temperature and strongly
      decrease the T-orthorhombic (O) and O-rhombohedral (R) transition. This unique
      ferroelectric phase evolution is attributed to Ca off-centering effects. More
      importantly, lowering of the T-O or O-R phase transitions allows us to prepare
      the piezoelectric ceramics with a strain response as high as S/E ~ 800 pm V(-1)
      (E = 10 kV cm(-1)) over a wide range of compositions with x ~ 0.1-0.18 at room
      temperature, which may be interesting for piezoelectric applications.

PMID- 24084570
TI  - Generation of topically transgenic rats by in utero electroporation and in vivo
      bioluminescence screening.
AB  - In utero electroporation (IUE) is a technique which allows genetic modification
      of cells in the brain for investigating neuronal development. So far, the use of
      IUE for investigating behavior or neuropathology in the adult brain has been
      limited by insufficient methods for monitoring of IUE transfection success by non
      invasive techniques in postnatal animals. For the present study, E16 rats were
      used for IUE. After intraventricular injection of the nucleic acids into the
      embryos, positioning of the tweezer electrodes was critical for targeting either
      the developing cortex or the hippocampus. Ventricular co-injection and
      electroporation of a luciferase gene allowed monitoring of the transfected cells
      postnatally after intraperitoneal luciferin injection in the anesthetized live P7
      pup by in vivo bioluminescence, using an IVIS Spectrum device with 3D
      quantification software. Area definition by bioluminescence could clearly
      differentiate between cortical and hippocampal electroporations and detect a
      signal longitudinally over time up to 5 weeks after birth. This imaging technique
      allowed us to select pups with a sufficient number of transfected cells assumed
      necessary for triggering biological effects and, subsequently, to perform
      behavioral investigations at 3 month of age. As an example, this study
      demonstrates that IUE with the human full length DISC1 gene into the rat cortex
      led to amphetamine hypersensitivity. Co-transfected GFP could be detected in
      neurons by post mortem fluorescence microscopy in cryosections indicating gene
      expression present at >=6 months after birth. We conclude that postnatal
      bioluminescence imaging allows evaluating the success of transient transfections
      with IUE in rats. Investigations on the influence of topical gene manipulations
      during neurodevelopment on the adult brain and its connectivity are greatly
      facilitated. For many scientific questions, this technique can supplement or even
      replace the use of transgenic rats and provide a novel technology for behavioral
      neuroscience. 

PMID- 24084571
TI  - An orthotopic murine model of human prostate cancer metastasis.
AB  - Our laboratory has developed a novel orthotopic implantation model of human
      prostate cancer (PCa). As PCa death is not due to the primary tumor, but rather
      the formation of distinct metastasis, the ability to effectively model this
      progression pre-clinically is of high value. In this model, cells are directly
      implanted into the ventral lobe of the prostate in Balb/c athymic mice, and
      allowed to progress for 4-6 weeks. At experiment termination, several distinct
      endpoints can be measured, such as size and molecular characterization of the
      primary tumor, the presence and quantification of circulating tumor cells in the
      blood and bone marrow, and formation of metastasis to the lung. In addition to a
      variety of endpoints, this model provides a picture of a cells ability to invade
      and escape the primary organ, enter and survive in the circulatory system, and
      implant and grow in a secondary site. This model has been used effectively to
      measure metastatic response to both changes in protein expression as well as to
      response to small molecule therapeutics, in a short turnaround time. 

PMID- 24084572
TI  - Mutation of fibulin-1 causes a novel syndrome involving the central nervous
      system and connective tissues.
AB  - Fibulin-1 is an extracellular matrix protein that has an important role in the
      structure of elastic fibers and basement membranes of various tissues. Using
      homozygosity mapping and exome sequencing, we discovered a missense mutation,
      p.(Cys397Phe), in fibulin-1 in three patients from a consanguineous family
      presented with a novel syndrome of syndactyly, undescended testes, delayed motor
      milestones, mental retardation and signs of brain atrophy. The mutation
      discovered segregated with the phenotype and was not found in 374 population
      matched alleles. The affected cysteine is highly conserved across vertebrates and
      its mutation is predicted to abolish a disulfide bond that defines the tertiary
      structure of fibulin-1. Our findings emphasize the crucial role fibulin-1 has in
      development of the central nervous system and various connective tissues. 

PMID- 24084573
TI  - B3GALNT2 is a gene associated with congenital muscular dystrophy with brain
      malformations.
AB  - Congenital muscular dystrophies associated with brain malformations are a group
      of disorders frequently associated with aberrant glycosylation of alpha
      dystroglycan. They include disease entities such a Walker-Warburg syndrome,
      muscle-eye-brain disease and various other clinical phenotypes. Different genes
      involved in glycosylation of alpha-dystroglycan are associated with these
      dystroglycanopathies. We describe a 5-year-old girl with psychomotor retardation,
      ataxia, spasticity, muscle weakness and increased serum creatine kinase levels.
      Immunhistochemistry of skeletal muscle revealed reduced glycosylated alpha
      dystroglycan. Magnetic resonance imaging of the brain at 3.5 years of age showed
      increased T2 signal from supratentorial and infratentorial white matter, a
      hypoplastic pons and subcortical cerebellar cysts. By whole exome sequencing, the
      patient was identified to be compound heterozygous for a one-base duplication and
      a missense mutation in the gene B3GALNT2 (beta-1,3-N
      acetylgalactosaminyltransferase 2; B3GalNAc-T2). This patient showed a milder
      phenotype than previously described patients with mutations in the B3GALNT2 gene.

PMID- 24084574
TI  - Identification of potential microRNA-target pairs associated with osteopetrosis
      by deep sequencing, iTRAQ proteomics and bioinformatics.
AB  - MicroRNAs aberrantly express in many human diseases including some metabolic bone
      disorders. They have been found to be associated with osteoclast differentiation
      and function, which makes them attractive candidates for the therapy of bone.
      However, the potential clinical application of microRNAs in therapeutics rests
      heavily upon our in-depth understanding of microRNAs and their targets. To
      identify potential microRNA-target pairs associated with osteopetrosis, we
      performed a system approach including deep sequencing, iTRAQ quantitative
      proteomics, and bioinformatics in the peripheral blood mononuclear cells (PBMCs)
      taken from patients with osteopetrosis and health donors. Notably, 123
      differently expressed microRNAs, 173 differently expressed proteins, and 117
      computationally predicted microRNA-target pairs with reciprocally expressed level
      in PBMCs were found in the two sample groups. Functional annotation identified
      that the microRNA-target pairs were involved in cell growth, differentiation,
      cellular signaling network, and the network highlighted the microRNA-target pair
      of has-miR-320a and ADP ribosylation factor 1 (Arf1) potentially associated with
      CLCN7 mutations in osteopetrosis. The pair of has-miR-320a and Arf1 was further
      verified by real-time PCR, western blot, and the interaction between has-miR-320a
      and its targeted sequence on the Arf1 mRNAs was confirmed by luciferase assay.
      Collectively, the present study established a new system approach for the
      investigation of microRNAs, and the microRNA-target pairs, particular has-miR
      320a and Arf1, may have important roles in osteopetrosis. 

PMID- 24084575
TI  - The MLH1 c.-27C>A and c.85G>T variants are linked to dominantly inherited MLH1
      epimutation and are borne on a European ancestral haplotype.
AB  - Germline mutations of the DNA mismatch repair genes MLH1, MSH2, MSH6 or PMS2, and
      deletions affecting the EPCAM gene adjacent to MSH2, underlie Lynch syndrome by
      predisposing to early-onset colorectal, endometrial and other cancers. An
      alternative but rare cause of Lynch syndrome is constitutional epimutation of
      MLH1, whereby promoter methylation and transcriptional silencing of one allele
      occurs throughout normal tissues. A dominantly transmitted constitutional MLH1
      epimutation has been linked to an MLH1 haplotype bearing two single-nucleotide
      variants, NM_000249.2: c.-27C>A and c.85G>T, in a Caucasian family with Lynch
      syndrome from Western Australia. Subsequently, a second seemingly unrelated
      Caucasian Australian case with the same MLH1 haplotype and concomitant
      epimutation was reported. We now describe three additional, ostensibly unrelated,
      cancer-affected families of European heritage with this MLH1 haplotype in
      association with constitutional epimutation, bringing the number of index cases
      reported to five. Array-based genotyping in four of these families revealed
      shared haplotypes between individual families that extended across <=2.6-<=6.4
      megabase regions of chromosome 3p, indicating common ancestry. A minimal <=2.6
      megabase founder haplotype common to all four families was identified, which
      encompassed MLH1 and additional flanking genes and segregated with the MLH1
      epimutation in each family. Our findings indicate that the MLH1 c.-27C>A and
      c.85G>T variants are borne on a European ancestral haplotype and provide
      conclusive evidence for its pathogenicity via a mechanism of epigenetic silencing
      of MLH1 within normal tissues. Additional descendants bearing this founder
      haplotype may exist who are also at high risk of developing Lynch syndrome
      related cancers. 

PMID- 24084576
TI  - The neuroprotective effects of ipriflavone against H 2O 2 and amyloid beta
      induced toxicity in human neuroblastoma SH-SY5Y cells.
AB  - Estrogenic compounds have been shown to have great potential for the treatment of
      Alzheimer's disease as demonstrated by its ability to antagonize amyloid beta
      peptide (Abeta) induced toxicity, the hallmark of Alzheimer's disease. Key
      mechanisms include the involvements of both the antioxidant and the anti
      apoptotic pathways. However, side effects of estrogens, such as the increased
      incidence of breast cancer, are of concern for further clinical translation.
      Approaches to overcome such barriers include the structural modification of
      estrogenic compounds and the search of phytoestrogens, but these are a long way
      from being translated into the clinic. We identified a compound similar in
      structure to human estrogen-ipriflavone, an over-the-counter product marketed in
      the United States for the treatment of osteoporosis, efficiently antagonized
      Abeta induced toxicity. Use of a model with SH-SY5Y neural cells, we first
      demonstrated that ipriflavone potently alleviated H2O2 induced cell death,
      reduced H2O2 induced elevations of both reactive oxygen species level and
      apoptosis. We extended our exploration of ipriflavone to Abeta and observed
      similar effects. These protective effects were comparable to those produced by
      17beta-estradiol at similar concentrations. Caspase-3 inhibition, PI3K and MAPK
      activation were shown to be responsible for such antagonism of ipriflavone on
      Abeta. Our results suggest that ipriflavone, a previously characterized compound,
      has great potential for expedited clinical translation for the treatment of
      Alzheimer's disease. 

PMID- 24084577
TI  - Effect of COMT Val(158)Met genotype on nicotine withdrawal-related cognitive
      dysfunction in smokers with and without schizophrenia.

PMID- 24084578
TI  - Elucidating neuroanatomical alterations in the at risk mental state and first
      episode psychosis: a combined voxel-based morphometry and voxel-based cortical
      thickness study.
AB  - Previous studies have reported alterations in grey matter volume and cortical
      thickness in individuals at high risk of developing psychosis and patients in the
      early stages of the disorder. Because these studies have typically focused on
      either grey matter volume or cortical thickness separately, the relationship
      between these two types of alterations is currently unclear. In the present
      investigation we used both voxel-based cortical thickness (VBCT) and voxel-based
      morphometry (VBM) to examine neuroanatomical differences in 21 individuals with
      an At Risk Mental State (ARMS) for psychosis, 26 patients with a First Episode of
      Psychosis (FEP) and 24 healthy controls. Statistical inferences were made at
      P<0.05 after correction for multiple comparisons. Cortical thinning in the right
      superior temporal gyrus was observed in both individuals at high risk of
      developing psychosis and patients with a first episode of the disorder, and
      therefore is likely to represent a marker of vulnerability. In contrast, the
      right posterior cingulate cortex showed cortical thinning in FEP patients
      relative to individuals at high risk, and therefore appears to be implicated in
      the onset of the disease. These neuroanatomical differences were expressed in
      terms of cortical thickness but not in terms of grey matter volume, and therefore
      may reflect specific cortical atrophy as opposed to variations in sulcal and
      gyral morphology. 

PMID- 24084579
TI  - Control of pathogen growth and biofilm formation using a urinary catheter that
      releases antimicrobial nitrogen oxides.
AB  - Antibacterial nitrogen oxides including nitric oxide are formed from nitrite
      under acidic conditions. In a continuous-flow model of the urinary bladder we
      used the retention cuff of an all-silicone Foley catheter as a depot for export
      of nitrogen oxides. The cuff was filled with sodium nitrite (50mM) and an acidic
      buffer solution (pH 3.6) and the growth of nine common uropathogens in the
      surrounding artificial urine was measured along with biofilm formation on the
      catheter surface. In experiments with control catheters (NaCl) bacteria grew
      readily and biofilm developed within hours in five of nine strains. In contrast,
      with test catheters bacterial counts were markedly reduced and biofilm formation
      by Pseudomonas aeruginosa, Klebsiella pneumoniae, and Enterobacter cloace was
      prevented, whereas Escherichia coli and Staphylococcus aureus were unaffected. We
      conclude that antibacterial nitrogen oxides generated in the retention cuff of a
      urinary catheter diffuse into urine and prevent the growth of urinary pathogens
      and biofilm formation. Although promising, future studies will reveal if this
      novel approach can be clinically useful for the prevention of catheter-associated
      urinary tract infections. 

PMID- 24084580
TI  - Letter to editor: concerning the comments "Silicon species in seawater" by
      Professor Exley and Professor Sjoberg.

PMID- 24084581
TI  - Anion sensing and F(-)-induced reversible photoreaction of D-pi-A type dye
      containing imidazole moiety as donor.
AB  - A new donor-pi-acceptor (D-pi-A) type dye was synthesized by the condensation
      reaction between 2-cyanomethylene-3-cyano-4,5,5-trimethyl-2,5-dihydrofuran and 4
      imidazolecarboxaldehyde. The chemical structure of the dye was characterized by
      (1)H NMR, EA and MS. A novel chromogenic dye based on imidazole as donor unit and
      furan as acceptor unit displayed marked UV-visible absorption changes in the
      presence of fluoride ion. The levels of energy potential and the electron density
      distributions of this dye were also simulated and discussed using computational
      model calculation. The reversible photoreaction of the dye-F(-) complex was
      studied by time-dependent UV-visible absorption spectra. 

PMID- 24084582
TI  - Methylphenidate place conditioning in adolescent rats: an analysis of sex
      differences and the dopamine transporter.
AB  - In two experiments, we analyzed the effects of methylphenidate (MPH) on
      conditioned place preference (CPP) in adolescent male and female rats, and the
      effects of MPH on the dopamine transporter (DAT). In Experiment 1, male and
      female rats were conditioned for 5 consecutive days from postnatal day (P)44 to
      P48 with saline, 1, or 5mg/kg MPH. On the post conditioning preference test, the
      group administered the 1mg/kg dose of MPH resulted in no significant preference
      compared to controls, whereas the 5mg/kg dose of MPH produced a robust
      significant preference for the paired context, but there were no sex differences.
      Analysis of the DAT revealed that animals conditioned with the 5mg/kg dose of MPH
      demonstrated a significant decrease of the dopamine transporter (DAT) in the
      nucleus accumbens and striatum compared to controls. In Experiment 2, animals
      were conditioned using an every second day paradigm from P33-41 to model a
      previous MPH treatment regimen that had revealed sex differences in behavioral
      sensitization. MPH produced an increased preference for the paired context on a
      post-conditioning preference test in Experiment 2, but as in Experiment 1, no sex
      differences were observed. These data show that a relatively high dose of MPH has
      rewarding associative effects in both adolescent male and female rats reliably
      across two different conditioning paradigms and ages in adolescence, but no sex
      difference. In addition, MPH results in a significant decrease of the DAT in drug
      reward brain areas which has implications toward plasticity of the brain's reward
      system. 

PMID- 24084583
TI  - Individual differences in activity levels in zebrafish (Danio rerio).
AB  - Individual differences and variation in behavioral responses have been identified
      in many animal species. These differences may be the result of genetic or
      environmental factors or the interaction between them. Analysis of individual
      differences in behavior may be important for many reasons. The zebrafish is a
      powerful model organism that is rapidly gaining popularity in behavioral brain
      research. However, individual differences have rarely been explored in zebrafish
      although significant variation in their performance has been reported. In the
      current study we identified individual differences in activity levels of
      zebrafish using a genetically heterogeneous population. Groups of zebrafish
      classified as high, medium, or low activity performers demonstrated consistent
      activity levels over a period of 7 days, and also in a subsequent open field
      task, suggesting stable individual differences as opposed to stochastic variation
      among subjects. We also uncovered a sex dependent relationship between behavioral
      measures. Female zebrafish in the high activity group preferred the top portion
      of the tank, whereas low activity females preferred the lower portion but males
      did not show such a relationship. The relationship between these two behaviors in
      females implies the potential existence of a behavioral syndrome persisting
      between contexts. Furthermore, females demonstrated a higher level of consistency
      in their behavior as compared to males, and the behavioral differences were found
      to be independent of both body size and weight of the tested subjects. The
      identification of individual differences in activity levels in zebrafish will
      allow the investigation of underlying genetic and/or environmental underpinnings.

PMID- 24084584
TI  - Isolation, culture, and functional characterization of adult mouse
      cardiomyoctyes.
AB  - The use of primary cardiomyocytes (CMs) in culture has provided a powerful
      complement to murine models of heart disease in advancing our understanding of
      heart disease. In particular, the ability to study ion homeostasis, ion channel
      function, cellular excitability and excitation-contraction coupling and their
      alterations in diseased conditions and by disease-causing mutations have led to
      significant insights into cardiac diseases. Furthermore, the lack of an adequate
      immortalized cell line to mimic adult CMs, and the limitations of neonatal CMs
      (which lack many of the structural and functional biomechanics characteristic of
      adult CMs) in culture have hampered our understanding of the complex interplay
      between signaling pathways, ion channels and contractile properties in the adult
      heart strengthening the importance of studying adult isolated cardiomyocytes.
      Here, we present methods for the isolation, culture, manipulation of gene
      expression by adenoviral-expressed proteins, and subsequent functional analysis
      of cardiomyocytes from the adult mouse. The use of these techniques will help to
      develop mechanistic insight into signaling pathways that regulate cellular
      excitability, Ca(2+) dynamics and contractility and provide a much more
      physiologically relevant characterization of cardiovascular disease. 

PMID- 24084586
TI  - The long-term effects of lifestyle change on blood pressure: One-year follow-up
      of the ENCORE study.
AB  - BACKGROUND: There is a paucity of data describing the sustained benefits of
      lifestyle interventions on health behaviors and blood pressure (BP). METHODS: We
      examined the persistence of changes in health habits and BP in the ENCORE study,
      a trial in which 144 overweight individuals with above-normal BP were randomized
      to one of the following 16-week interventions: Dietary Approaches to Stop
      Hypertension (DASH) diet alone (DASH-A), DASH diet plus a behavioral weight
      management intervention (DASH-WM), or Usual Care. Follow-up assessments were
      conducted 8 months after the end of treatment. RESULTS: At 16 weeks, systolic BP
      was reduced by 16.1 (95% confidence interval (CI) = 13.0-19.2) mm Hg in the DASH
      WM group, 11.2 (95% CI = 8.1-14.3) mm Hg in the DASH-A group, and 3.4 (95% CI =
      0.4-6.4) mm Hg in the Usual Care group. A decrease in BP persisted for 8 months,
      with systolic BP lower than baseline by 11.7 (95% CI = 8.1-15.3) mm Hg in the
      DASH-WM group, 9.5 (95% CI = 6.7-12.1) mm Hg in the DASH-A group, and 3.9 (95% CI
      = 0.5-7.3) mm Hg in the Usual Care group (P < 0.001 for active treatments vs.
      Usual Care). DASH-WM subjects lost 8.7 kg during the intervention and remained
      6.3 kg lighter on follow-up examination. Changes in diet content were sustained
      in both DASH intervention groups. Among those who participated in DASH-WM,
      however, caloric intake was no longer lower, and only 21% reported still
      exercising regularly 8 months after completing the intervention. CONCLUSIONS:
      Changes in dietary habits, weight, and BP persisted for 8 months after completion
      of the 16-week ENCORE program, with some attenuation of the benefits. Additional
      research is needed to identify effective methods to promote long-term maintenance
      of the benefits of lifestyle modification programs. CLINICAL TRIAL REGISTRATION:
      Clinicaltrials.gov identifier: NCT00571844.

PMID- 24084587
TI  - Perioperative Diastolic Dysfunction: A Comprehensive Approach to Assessment by
      Transesophageal Echocardiography.
AB  - Left ventricular diastolic dysfunction (LVDD) has only recently been recognized
      as an important determinant of perioperative morbidity. Intraoperative
      echocardiographers have been slow to adopt assessment of LVDD into clinical
      practice. This has been partly attributable to the complex measurements required
      to characterize LVDD, which are in turn related to how our understanding of
      diastole has evolved. Additionally, the lack of effective therapeutic options has
      left many wondering whether it is worthwhile to characterize this pathology in
      the first place. However, therapies are developed more rapidly once a problem can
      be identified reliably. The assessment of LVDD is centered on how effectively the
      left ventricle can fill. Diastolic dysfunction affects intraventricular pressures
      and stiffness, which in turn affect the pressure relationship between the left
      atrium and the left ventricle thereby affecting transmitral flow. Since
      echocardiography can enable the measurement of flow velocities, transmitral
      diastolic filling flow patterns provide robust information on diastolic function.
      The impact of abnormal diastolic function on left atrial pressure has
      consequences for pulmonary venous flow, which can also be measured with
      echocardiography. However, given the limitations of flow velocity, direct
      measurement of tissue velocity can significantly improve the characterization of
      diastolic dysfunction. The evolution of Doppler and speckle-based methods of
      assessing tissue motion have vastly improved our understanding of diastolic
      function. With the development of simpler algorithms for categorization, and
      their gradual adoption by perioperative echocardiographers, LVDD should be better
      diagnosed and treated to improve postoperative outcomes. 

PMID- 24084585
TI  - Dissecting regulation mechanism of the FMN to heme interdomain electron transfer
      in nitric oxide synthases.
AB  - Nitric oxide synthase (NOS), a flavo-hemoprotein, is responsible for biosynthesis
      of nitric oxide (NO) in mammals. Three NOS isoforms, iNOS, eNOS and nNOS
      (inducible, endothelial, and neuronal NOS), achieve their biological functions by
      tight control of interdomain electron transfer (IET) process through interdomain
      interactions. In particular, the FMN-heme IET is essential in coupling electron
      transfer in the reductase domain with NO synthesis in the heme domain by delivery
      of electrons required for O2 activation at the catalytic heme site. Emerging
      evidence indicates that calmodulin (CaM) activates NO synthesis in eNOS and nNOS
      by a conformational change of the FMN domain from its shielded electron-accepting
      (input) state to a new electron-donating (output) state, and that CaM is also
      required for proper alignment of the FMN and heme domains in the three NOS
      isoforms. In the absence of a structure of full-length NOS, an integrated
      approach of spectroscopic, rapid kinetic and mutagenesis methods is required to
      unravel regulation mechanism of the FMN-heme IET process. This is to investigate
      the roles of the FMN domain motions and the docking between the primary
      functional FMN and heme domains in regulating NOS activity. The recent
      developments in this area that are driven by the combined approach are the
      focuses of this review. A better understanding of the roles of interdomain
      FMN/heme interactions and CaM binding may serve as a basis for the rational
      design of new selective modulators of the NOS enzymes. 

PMID- 24084589
TI  - Advancing plant phenology and reduced herbivore production in a terrestrial
      system associated with sea ice decline.
AB  - The contribution of declining Arctic sea ice to warming in the region through
      Arctic amplification suggests that sea ice decline has the potential to influence
      ecological dynamics in terrestrial Arctic systems. Empirical evidence for such
      effects is limited, however, particularly at the local population and community
      levels. Here we identify an Arctic sea ice signal in the annual timing of
      vegetation emergence at an inland tundra system in West Greenland. According to
      the time series analyses presented here, an ongoing advance in plant phenology at
      this site is attributable to the accelerating decline in Arctic sea ice, and
      contributes to declining large herbivore reproductive performance via trophic
      mismatch. Arctic-wide sea ice metrics consistently outperform other regional and
      local abiotic variables in models characterizing these dynamics, implicating
      large-scale Arctic sea ice decline as a potentially important, albeit indirect,
      contributor to local-scale ecological dynamics on land. 

PMID- 24084588
TI  - The THO complex component Thp2 counteracts telomeric R-loops and telomere
      shortening.
AB  - Telomere maintenance by the conventional DNA replication machinery and telomerase
      is assisted by specialized DNA helicases, nucleases and telomere binding
      proteins. Here, we identify the THO components at telomeres and define critical
      roles of this complex in telomere stability. Deletion of the THO-subunit THP2
      leads to telomere shortening. We discover that telomeres contain RNA:DNA hybrid
      structures or R-loops which involve the long-noncoding RNA TERRA and which
      accumulate in thp2-Delta cells. Telomere length is not restored by R-loop removal
      upon RNase H overexpression, but by deletion of Exonuclease 1 (Exo1). Replication
      stress further enhances the short telomere phenotype of THP2 mutants. Similar
      events occur upon induced transcription of TERRA and genetic analysis links Thp2
      to TERRA function. Altogether, our data indicate that THO, through the interplay
      with TERRA, regulates chromosome end processing activities and prevents
      interference with semiconservative DNA replication of telomeric DNA. 

PMID- 24084591
TI  - Fundamentals of flexoelectricity in solids.
AB  - The flexoelectric effect is the response of electric polarization to a mechanical
      strain gradient. It can be viewed as a higher-order effect with respect to
      piezoelectricity, which is the response of polarization to strain itself.
      However, at the nanoscale, where large strain gradients are expected, the
      flexoelectric effect becomes appreciable. Besides, in contrast to the
      piezoelectric effect, flexoelectricity is allowed by symmetry in any material.
      Due to these qualities flexoelectricity has attracted growing interest during the
      past decade. Presently, its role in the physics of dielectrics and semiconductors
      is widely recognized and the effect is viewed as promising for practical
      applications. On the other hand, the available theoretical and experimental
      results are rather contradictory, attesting to a limited understanding in the
      field. This review paper presents a critical analysis of the current knowledge on
      the flexoelectricity in common solids, excluding organic materials and liquid
      crystals. 

PMID- 24084590
TI  - Altered functional connectivity of basal ganglia circuitry in dental phobia.
AB  - Recent symptom provocation studies that compared patients suffering from dental
      phobia with healthy controls identified hyperactivation of basal ganglia
      structures, but none have assessed striatal functional connectivity. We
      reanalyzed data from a previous functional magnetic resonance imaging study on
      dental phobia. Patients (20 men, 25 women) and healthy controls (18 men, 23
      women) had been exposed to pictures showing dental treatment, and neutral
      contents. We conducted connectivity analyses via psychophysiological interactions
      (PPIs). Relative to non-phobic controls, the patients showed decreased
      connectivity between prefrontal and basal ganglia regions. Moreover, the clinical
      group was characterized by increased internal basal ganglia connectivity, which
      was more pronounced in female compared with male patients. This study provides
      first evidence for an altered information flow within a fronto-striatal network
      in dentophobic individuals during visual symptom provocation, which can be
      considered a neuromarker of this disorder.

PMID- 24084592
TI  - Assessment of the role of cortisol and corticosteroid receptors in epidermal
      ionocyte development in the medaka (Oryzias latipes) embryos.
AB  - Cortisol is a pleiotropic glucocorticoid hormone that acts through the
      intracellular glucocorticoid receptors (GR). Cortisol affects many important
      biological functions in mammals, including immune function, behavior, stress,
      metabolism, growth and organogenesis. In fishes, cortisol has an additional
      function in the osmoregulatory activity of ionocytes (ICs). Although much
      progress has been made toward understanding cortisol action at the levels of
      adult osmoregulatory tissues, the developmental functions of cortisol and its
      receptors in ICs remain to be clarified. We first analyzed the total contents of
      both cortisol and corticosteroid receptor mRNAs (GR1, GR2 and MR) during medaka
      development. Although low levels of cortisol were detected during development of
      the medaka embryo, maternal GR1, GR2 and MR transcripts were detected at higher
      levels than zygotic transcripts. We investigated the effect of exogenous cortisol
      on IC number during medaka embryogenesis. We observed that cortisol treatment
      induced an earlier expansion of the IC population but did not modify the final IC
      number. Using functional genomic approaches, we also tested the involvement of
      GR1, GR2 and mineralocorticoid receptor (MR) in IC development by systematic
      knock-down with translation-blocking morpholinos. Only GR2 knock-down led to a
      reduction of the total number of ICs in the epidermis. In addition, a GR2 splice
      blocking morpholino did not have any effect on the biogenesis of ICs,
      underscoring the importance of maternally inherited GR2 mRNAs. We propose that
      maternal GR2, but not GR1 or MR, is a major pathway in the IC biogenesis in
      medaka most likely through cortisol activation, and that cortisol exposition fine
      tunes their developmental timing. These findings provide a framework for future
      research on the regulatory functions of corticosteroids in euryhaline fishes and
      provide medaka as an advantageous model to further elucidate the underlying
      molecular regulatory mechanisms of IC development. 

PMID- 24084593
TI  - Scube regulates synovial angiogenesis-related signaling.
AB  - Angiogenesis is particularly driven in the synovial microenvironment of
      Rheumatoid arthritis (RA), and considered as the fundamental cause for the
      persistent injury and chronic damage. Therefore, exploring the pathomechanism of
      synovial angiogenesis may provide promising prospects for vascular-targeting
      treatment of RA. The noval family of Scube proteins is confirmed to overlap
      significantly in structure characterized by epidermal growth factor (EGF)-like
      domains and CUB (complement subcomponents C1r/C1s, Uegf, bone morphogenetic
      protein-1) domain. As secreted glycoprotein and peripheral membrane protein,
      Scube increases its serum level in response to stimuli of inflammation and
      hypoxia. In rheumatoid angiogenesis-related signaling system defined by hedgehog
      (Hh), transforming growth factor (TGF)beta and bone morphogenetic protein 2
      (BMP2), Scube1 and 2 antagonize BMP2 signaling, suppressing BMP2-induced phospho
      Smad1/5/8 level in vivo. Scube3 functions as an endogenous TGFbeta receptor
      ligand, increasing Smad2/3 phosphorylation, and thus upregulates target genes
      involved in angiogenesis. Via obligate assistance of Scube1 and 3, Scube2 plays a
      center role to recruit dually lipid-modified Hh transferred from Dispatched A
      (DispA), increasing Hh secretion by promoting its solubility. These findings
      support the hypothesis that Scube may regulate synovial angiogenesis may be the
      ideal vascular targets for anti-rheumatic treatment of RA. 

PMID- 24084594
TI  - The application of thionine-graphene nanocomposite in chiral sensing for
      Tryptophan enantiomers.
AB  - The thionine-graphene (THi-GR, positively charged) nanocomposite was successfully
      synthesized as a good biocompatible matrix for ds-DNA which acted as a chiral
      selector to construct an electrochemical chiral biosensor for Tryptophan (Trp)
      enantiomers sensing with the assistance of Cu(II). The nano-bionic interface was
      constructed as follows: Firstly, the nanocomposite was dropped on the surface of
      glassy carbon electrode (GCE), and then ds-DNA (negatively charged) was
      immobilized onto the nanocomposite film via the opposite-charged adsorption
      techniques. This biofunctionalized nanocomposite was characterized with scanning
      electron microscopy (SEM), ultraviolet-visible (UV-vis) spectrometry and cyclic
      voltammetry (CV). The chiral biosensor was employed to study the recognition
      effect between ds-DNA and Trp enantiomers by CV. The results show that larger
      electrochemical response was obtained from l-Trp when Cu(II) was present,
      indicating this strategy could be employed to enantioselectively recognize Trp
      enantiomers. Under optimum conditions, the chiral biosensor exhibited a good
      linear response to Trp enantiomers in the range of the concentration of
      [Cu(II)(Trp)2] from 5.0 * 10(-4) to 2.5mM with a low limit of detection of 0.17
      MUM (S/N=3). The binding constant was calculated to be 2.97 * 10(3)M(-1) for
      [Cu(II)(l-Trp)2] and 2.50 * 10(2)M(-1) for [Cu(II)(d-Trp)2].

PMID- 24084595
TI  - Neuroendocrine carcinomas: optimal surgery of peritoneal metastases (and
      associated intra-abdominal metastases).
AB  - AIM: To report the results of complete cytoreductive surgery (CCRS) of peritoneal
      metastases from neuroendocrine tumor (NET) and to compare patients treated with
      or without hyperthermic intraperitoneal chemotherapy (HIPEC). BACKGROUND:
      Aggressive management of peritoneal metastases from NET (in most of the cases
      associated with other types of metastases) has not been addressed in the
      literature, but these metastases affect overall survival. PATIENTS AND METHODS:
      From 1994 to 2012, 41 patients underwent CCRS, with HIPEC (n = 28) from 1994 to
      2007 but without HIPEC (n = 13) from 2008 to 2012. Liver metastases were treated
      during the same operative procedure in 66% of the patients. RESULTS: Mortality
      was 2% and morbidity 56%. Overall survival at 5 and 10 years was 69% and 52%,
      respectively, and disease-free survival at 5 and 10 years was 17% and 6%,
      respectively. At 5 years, peritoneal metastases and liver metastases recurred in
      47% and in 66% of cases, respectively. Overall survival was not different between
      patients treated with or without HIPEC, but disease-free survival was greater in
      the HIPEC group (P = .018), mainly because of fewer lung and bone metastases.
      CONCLUSION: CCRS of peritoneal metastases from a NET is feasible in most of the
      patients and seems to increase survival rates. We were unable to determine
      whether adding HIPEC had a positive or a negative impact.

PMID- 24084596
TI  - RECK regulated endoplasmic reticulum stress response and enhanced cisplatin
      induced cell death in neuroblastoma cells.
AB  - BACKGROUND: Reversion-inducing-cysteine-rich protein with Kazal motifs (RECK) is
      critical for the invasiveness and metastasis of tumor cells; however, its role in
      regulating the endoplasmic reticulum (ER) stress response remains unclear. In
      this study we investigated the protein that interacts with RECK and the effects
      of RECK overexpression on the ER stress response and on cisplatin-induced cell
      death in neuroblastoma cells. METHODS: Full-length RECK (FL-RECK) or a C-terminus
      deleted mutant of RECK (del-C-RECK) was transfected into neuroblastoma cells. An
      immunoprecipitation (IP) assay and liquid chromatography with tandem mass
      spectrometry (LC-MS/MS) analysis were used to identify the RECK-interacting
      proteins. The interaction between RECK and these proteins was confirmed using co
      IP and an immunofluorescence assay. Phosphorylation of double-stranded, RNA
      activated protein kinase-like, ER-localized eukaryotic initiation factor-2alpha
      (eIF-2alpha) kinase (PERK) and eIF-2alpha, and expression of ER stress-related
      apoptotic factors were studied by Western blot analysis. RESULTS: Glucose
      regulated protein 78 (GRP78) was identified as the RECK-interacting protein in
      neuroblastoma cells, and the C-terminus region of the RECK protein was shown to
      interact with GRP78. Overexpression of FL-RECK, but not of del-C-RECK, increased
      the phosphorylation of PERK and eIF-2alpha in neuroblastoma cells. With cisplatin
      treatment, the expression of phosphorylated PERK and eIF-2alpha, CCAAT/enhancer
      binding protein-homologous protein, Bax, and caspase-4 and -7 was higher and the
      cell viability was lower (P < .01) in FL-RECK-overexpressing cells than in del-C
      RECK-overexpressing or vector control cells. CONCLUSION: RECK regulated the
      cellular ER stress response through interaction with GRP78 and enhanced cisplatin
      induced cell death in neuroblastoma cells.

PMID- 24084597
TI  - Operatively induced chronic reflux in rats: a suitable model for studying
      esophageal carcinogenesis?
AB  - BACKGROUND: The mechanisms of esophageal reflux leading to esophageal
      adenocarcinoma (EA) remain poorly understood. This study appraises critically an
      operatively induced chronic reflux rat model. METHODS: We randomized 108 Sprague
      Dawley rats into 2 experimental groups; one was performing esophagoduodenal (ED)
      anastomosis with or without gastrectomy to induce duodeno-esophageal reflux (DER
      group; n = 63), and the other involved duodeno-gastro-esophageal reflux (DGER
      group; n = 45). Control groups included (i) Roux-en-Y esophagojejunal
      anastomosis, (ii) laparotomy alone, (iii) subtotal gastrectomy to induce
      duodenogastric reflux (DGR group), and (iv) the same procedure as in the DGER
      group plus proton pump inhibition (PPI group). The esophagus underwent histologic
      and molecular analyses. RESULTS: The prevalence of Barrett's esophagus (BE),
      dysplasia, and EA in the experimental groups was 41%, 7%, and 11%, respectively.
      Histologic and molecular analyses in groups DER, DGER, and DGR suggested that BE
      occurred through de novo intestinal metaplasia and proximal migration of duodenal
      cells. No distant metastases were identified. The molecular characteristics of
      both BE and EA were similar to humans. BE was more common, and dysplasia and EA
      less frequent in the DER group when compared with the DGER group (44% vs 24% [P =
      .038] and 7% vs 25% [P = .012], respectively). Compared with the DGER group,
      carcinogenic sequence occurred less frequently in the PPI-treated group (P =
      .019). CONCLUSION: Despite pathophysiologic differences with humans, the rat
      model of esophagoduodenostomy reproduces accurately histologic and molecular
      lesions in the carcinogenetic sequence of BE and allowed us to identify novel,
      tumor-associated proteins that may be potential biomarkers and new therapeutic
      targets in EA.

PMID- 24084598
TI  - Intraoperative neuromonitoring for the early detection and prevention of RLN
      traction injury in thyroid surgery: a porcine model.
AB  - BACKGROUND: Operative traction of the thyroid lobe is a necessary component of
      thyroid surgery. This surgical maneuver can cause traction injury of the
      recurrent laryngeal nerve (RLN), and this complication has been reported to be
      the most common mechanism of nerve injury. The goal of this study was to
      investigate the electromyographic (EMG) signal pattern during an acute RLN
      traction injury and establish reliable strategies to prevent the injury using
      intraoperative neuromonitoring (IONM). METHODS: Fifteen piglets (30 RLNs)
      underwent IONM via automated periodic vagal nerve stimulation and had their EMG
      tracings recorded and correlated with various models of nerve injury. RESULTS: In
      the pilot study, a progressive, partial EMG loss was observed under RLN tractions
      with different tension (n = 8). The changes in amplitudes were more marked and
      consistent than were the changes in latency. The EMG gradually gained partial
      recovery after the traction was relieved. Among the nerves injured with
      electrothermal (n = 4), clamping (n = 1), and transection (n = 1) models, the EMG
      showed immediate partial or complete loss, and no gradual EMG recovery was
      observed. Another 16 RLNs were used to investigate the potential of EMG recovery
      after different extents of RLN traction. We noted the EMG showed nearly full
      recovery if the traction stress was relieved before the loss of signal (LOS), but
      the recovery was worse if prolonged or repeated traction was applied. The mean
      restored amplitudes after the traction was relieved before, during, and after the
      LOS were 98 +/- 3% (n = 6), 36 +/- 4% (n = 4), and 15 +/- 2% (n = 6),
      respectively. CONCLUSION: RLN traction injury showed graded, partial EMG changes;
      early release of the traction before the EMG has degraded to LOS offers a good
      chance of EMG recovery. IONM can be used as a tool for the early detection of
      adverse EMG changes that may alert surgeons to correct certain maneuvers
      immediately to prevent irreversible nerve injury during the thyroid operation.

PMID- 24084600
TI  - Bedside immunochromatographic test for enterovirus 71 infection in children.
AB  - BACKGROUND: Enterovirus 71 (EV71) causes frequent outbreaks worldwide,
      particularly in the Asia-Pacific area. Its quick spread is a critical challenge
      for public health and timely preventive measures and clinical management
      therefore rely on early detection. There is a need for a rapid, easy-to-use, and
      reliable method for detecting EV71 infections. OBJECTIVE: The study aimed to
      evaluate a bedside immunochromatography (ICT) kit for diagnosing acute EV71
      infection in children. STUDY DESIGN: Pediatric patients with herpangina or hand
      foot-mouth disease were randomly and prospectively enrolled from hospitals across
      Taiwan. Throat or rectal swabs were collected for viral culture and reverse
      transcriptase polymerase chain reaction (RTPCR). For the ICT kit, whole blood was
      obtained by ear piercing, finger-sticking, or venipuncture. The results of ICT,
      virus isolation and RTPCR in clinical samples were compared. RESULTS: Of the 156
      patients enrolled, 91 (58%), 64 (41%) and 72 (46%) had positive results of the
      ICT kit, viral culture and RTPCR, respectively. Laboratory-confirmed infection
      with either positive EV71 culture or RTPCR was used as the diagnostic standard.
      The sensitivity and specificity of the ICT kit was 84% and 77%, respectively. The
      viral culture and RTPCR had relatively lower sensitivity but higher specificity.
      The patient's age did not affect the performance of the ICT, viral culture and
      RTPCR. However, a low sensitivity of ICT kit was noted before the second day of
      disease onset. CONCLUSIONS: The ICT kit may serve as a simple, quick and reliable
      method for the bedside diagnosis of acute EV71 infection in children.

PMID- 24084599
TI  - Quantitative multispectral analysis following fluorescent tissue transplant for
      visualization of cell origins, types, and interactions.
AB  - With the desire to understand the contributions of multiple cellular elements to
      the development of a complex tissue; such as the numerous cell types that
      participate in regenerating tissue, tumor formation, or vasculogenesis, we
      devised a multi-colored cellular transplant model of tumor development in which
      cell populations originate from different fluorescently colored reporter gene
      mice and are transplanted, engrafted or injected in and around a developing
      tumor. These colored cells are then recruited and incorporated into the tumor
      stroma. In order to quantitatively assess bone marrow derived tumor stromal
      cells, we transplanted GFP expressing transgenic whole bone marrow into lethally
      irradiated RFP expressing mice as approved by IACUC. 0ovarian tumors that were
      orthotopically injected into the transplanted mice were excised 6-8 weeks post
      engraftment and analyzed for bone marrow marker of origin (GFP) as well as
      antibody markers to detect tumor associated stroma using multispectral imaging
      techniques. We then adapted a methodology we call MIMicc- Multispectral
      Interrogation of Multiplexed cellular compositions, using multispectral unmixing
      of fluoroprobes to quantitatively assess which labeled cell came from which
      starting populations (based on original reporter gene labels), and as our ability
      to unmix 4, 5, 6 or more spectra per slide increases, we've added additional
      immunohistochemistry associated with cell lineages or differentiation to increase
      precision. Utilizing software to detect co-localized multiplexed-fluorescent
      signals, tumor stromal populations can be traced, enumerated and characterized
      based on marker staining.

PMID- 24084601
TI  - Hepatitis E virus seroprevalence and risk factors for individuals in working
      contact with animals.
AB  - BACKGROUND: In industrial countries genotypes 3 and 4 of HEV are detected in
      swine, wild boar, deer and rabbits, and they are associated with autochthonous
      infections suggesting the existence of zoonotic HEV infections, compatible with
      the putative involvement of undercooked pork and big game products as a source of
      infection. OBJECTIVES: To evaluate the prevalence of anti-HEV antibodies in
      different population groups in contact with animals and to investigate risk
      factors for HEV infection. STUDY DESIGN: Serum samples were collected from 859
      healthy French subjects, including pig farm workers, forestry workers and
      individuals without working contact with animals (control group). In addition, 58
      swine veterinarians were included in the study. Subjects were interviewed using a
      structured questionnaire, and anti-HEV antibodies were investigated using a
      sensitive and specific sandwich ELISA. RESULTS: Anti-Hepatitis E virus (HEV)
      antibodies were detected in 26% of control population, and in 36% and 44% of
      forestry and pig farm workers, respectively. In addition, an increase in
      seroprevalence from the north to the south of France was observed (30.2% versus
      40.7%). Consumption of pork liver sausage (AOR 4.4, p < 10(-4)), occupational
      contact with animals (AOR 1.58, p = 0.038 for forestry workers and AOR 2.51, p <
      10(-4) for pig farm workers), and living in southern France (AOR 1.47, p = 0.02),
      were independent risk factors. Wearing working gloves and boots might reduce HEV
      infection. CONCLUSIONS: Occupational exposure to animals and consuming raw or
      undercooked pork liver sausage or pork liver play a significant role in HEV
      transmission in industrial countries.

PMID- 24084602
TI  - Wheat seed proteins regulated by imbibition independent of dormancy status.
AB  - Seed dormancy is an important trait in wheat (Trticum aestivum L.) and it can be
      released by germination-stimulating treatments such as after-ripening.
      Previously, we identified proteins specifically associated with after-ripening
      mediated developmental switches of wheat seeds from the state of dormancy to
      germination. Here, we report seed proteins that exhibited imbibition induced co
      regulation in both dormant and after-ripened seeds of wheat, suggesting that the
      expression of these specific proteins/protein isoforms is not associated with the
      maintenance or release of seed dormancy in wheat.

PMID- 24084603
TI  - Snf1/AMPK promotes SBF and MBF-dependent transcription in budding yeast.
AB  - Snf1, the yeast AMP-activated kinase homolog, regulates the expression of several
      genes involved in adaptation to glucose limitation and in response to cellular
      stresses. We previously demonstrated that Snf1 interacts with Swi6, the
      regulatory subunit of SBF and MBF complexes, and activates CLB5 transcription.
      Here we report that, in alpha-factor synchronized cells in 2% glucose, the loss
      of the Snf1 catalytic subunit impairs the binding of SBF and MBF complexes and
      the subsequent recruitment of the FACT complex and RNA Polymerase II to promoters
      of G1-genes. By using an analog-sensitive allele of SNF1, SNF1(as)(I132G),
      encoding a protein whose catalytic activity is selectively inhibited in vivo by 2
      naphthylmethyl pyrazolopyrimidine 1, we show that the inhibition of Snf1
      catalytic activity affects the expression of G1-genes causing a delayed entrance
      into S phase in cells synchronized in G1 phase by alpha-factor treatment or by
      elutriation. Moreover, Snf1 is detected in immune complexes of Rpb1, the large
      subunit of RNA Polymerase II, and is present at both promoters and coding regions
      of SBF- and MBF-regulated genes 20min after alpha-factor release, suggesting a
      direct role for Snf1 in the activation of the G1-regulon transcription. 

PMID- 24084604
TI  - Modification of carbon nanotube transparent conducting films for electrodes in
      organic light-emitting diodes.
AB  - Single-walled carbon nanotube (SWCNT) transparent conducting films (TCFs) were
      fabricated for the electrodes of organic light-emitting diodes (OLEDs); three
      types of film were studied. The as-prepared SWCNT TCFs displayed a relatively low
      sheet resistance of 82.6 Omega/sq at 80.7 T% with a relatively large surface
      roughness of 30 nm. The TCFs were top-coated with poly(3,4
      ethylenedioxythiophene):poly(styrene sulfonate) (PEDOT:PSS) to obtain PEDOT:PSS
      coated TCFs. The PEDOT:PSS cover improved the conductivity and decreased the
      surface roughness to 12 nm at the cost of film transmittance. The SWCNT TCFs
      mixed with PEDOT:PSS (PM-TCFs) exhibited a high conductivity (70.6 Omega/sq at 81
      T%) and a low surface roughness (3 nm) and were thus selected as the best TCFs
      for OLEDs. Blue flexible OLEDs with 4,4'-bis(2,2'-diphenylvinyl)-1,1'-biphenyl
      (Dpvbi) as the emitting layer were fabricated on TCFs with the same structures to
      evaluate the performances of the different types of SWCNT films for use in OLEDs.
      Of these three types of OLEDs, the PM-TCF devices exhibited the optimal
      performance with a maximum luminance of 2587 cd m(-2) and a current efficiency of
      5.44 cd A(-1). This result was explored using field-emission scanning electron
      microscopy and atomic force microscopy to further study the mechanisms that are
      involved in applying SWCNT TCFs to OLEDs.

PMID- 24084605
TI  - Calcium regulation by temperature-sensitive transient receptor potential channels
      in human uveal melanoma cells.
AB  - Uveal melanoma (UM) is both the most common and fatal intraocular cancer among
      adults worldwide. As with all types of neoplasia, changes in Ca(2+) channel
      regulation can contribute to the onset and progression of this pathological
      condition. Transient receptor potential channels (TRPs) and cannabinoid receptor
      type 1 (CB1) are two different types of Ca(2+) permeation pathways that can be
      dysregulated during neoplasia. We determined in malignant human UM and healthy
      uvea and four different UM cell lines whether there is gene and functional
      expression of TRP subtypes and CB1 since they could serve as drug targets to
      either prevent or inhibit initiation and progression of UM. RT-PCR, Ca(2+)
      transients, immunohistochemistry and planar patch-clamp analysis probed for their
      gene expression and functional activity, respectively. In UM cells, TRPV1 and
      TRPM8 gene expression was identified. Capsaicin (CAP), menthol or icilin induced
      Ca(2+) transients as well as changes in ion current behavior characteristic of
      TRPV1 and TRPM8 expression. Such effects were blocked with either La(3+),
      capsazepine (CPZ) or BCTC. TRPA1 and CB1 are highly expressed in human uvea, but
      TRPA1 is not expressed in all UM cell lines. In UM cells, the CB1 agonist, WIN
      55,212-2, induced Ca(2+) transients, which were suppressed by La(3+) and CPZ
      whereas CAP-induced Ca(2+) transients could also be suppressed by CB1 activation.
      Identification of functional TRPV1, TRPM8, TRPA1 and CB1 expression in these
      tissues may provide novel drug targets for treatment of this aggressive
      neoplastic disease. 

PMID- 24084606
TI  - Dependence of laser-induced breakdown spectroscopy results on pulse energies and
      timing parameters using soil simulants.
AB  - The dependence of some LIBS detection capabilities on lower pulse energies (<100
      mJ) and timing parameters were examined using synthetic silicate samples. These
      samples were used as simulants for soil and contained minor and trace elements
      commonly found in soil at a wide range of concentrations. For this study, over
      100 calibration curves were prepared using different pulse energies and timing
      parameters; detection limits and sensitivities were determined from the
      calibration curves. Plasma temperatures were also measured using Boltzmann plots
      for the various energies and the timing parameters tested. The electron density
      of the plasma was calculated using the full-width half maximum (FWHM) of the
      hydrogen line at 656.5 nm over the energies tested. Overall, the results indicate
      that the use of lower pulse energies and non-gated detection do not seriously
      compromise the analytical results. These results are very relevant to the design
      of field- and person-portable LIBS instruments. 

PMID- 24084607
TI  - Genetic parameters for meat quality traits of Australian lamb meat.
AB  - Genetic parameters were estimated for a range of meat quality traits recorded on
      Australian lamb meat. Data were collected from Merino and crossbred progeny of
      Merino, terminal and maternal meat breed sires of the Information Nucleus
      programme. Lambs born between 2007 and 2010 (n=8968) were slaughtered, these
      being the progeny of 372 sires and 5309 dams. Meat quality traits were found
      generally to be of moderate heritability (estimates between 0.15 and 0.30 for
      measures of meat tenderness, meat colour, polyunsaturated fat content, mineral
      content and muscle oxidative capacity), with notable exceptions of intramuscular
      fat (0.48), ultimate pH (0.08) and fresh meat colour a* (0.08) and b* (0.10)
      values. Genetic correlations between hot carcass weight and the meat quality
      traits were low. The genetic correlation between intramuscular fat and shear
      force was high (-0.62). Several measures of meat quality (fresh meat redness,
      retail meat redness, retail oxy/met value and iron content) appear to have
      potential for inclusion in meat sheep breeding objectives. 

PMID- 24084608
TI  - Survival with 98% methemoglobin levels in a school-aged child during the
      "festival of colors".
AB  - Methemoglobin levels more than 70% have almost always been reported to have been
      fatal. The case of a 4-year-old boy who survived with methemoglobin levels of 98%
      is presented here. He was brought to the emergency department with complaints of
      vomiting, pain abdomen, and altered sensorium following accidental ingestion of
      paint thinner mixed with "Holi" colors. On examination, the child was in altered
      sensorium, cyanosed with saturations of 55%, who did not respond despite positive
      pressure ventilation with 100% oxygen. A possibility of toxic methemoglobinemia
      was considered and confirmed by finding of elevated methemoglobin levels of 98%.
      The child survived with definitive therapy with methylene blue and aggressive
      goal-directed approach. 

PMID- 24084609
TI  - Pediatric mumps with laryngeal edema.
AB  - Mumps virus infection primarily affects the salivary glands and may incur various
      complications. Laryngeal edema is such a rare complication that few adult cases
      have been reported. We report the first known pediatric patient with mumps with
      laryngeal edema. An 8-year-old boy developed dyspnea after a rapidly progressive
      swelling of his face and neck. Laryngoscopy revealed edematous changes in the
      supraglottic and subglottic regions, and computed tomography confirmed
      significant laryngeal edema in addition to swelling of the cervical soft tissue
      and the salivary glands. Laboratory findings revealed a high serum amylase level
      and confirmed the diagnosis of mumps. Intravenous steroid administration
      alleviated the dyspnea, although the patient required temporary tracheal
      intubation to maintain airway patency. He did not need tracheotomy and did not
      experience any other complications. Laryngeal edema must be regarded as a rare,
      potentially life-threatening complication of mumps. When mumps is diagnosed with
      significant swelling of the neck, an emergency airway should be established to
      prevent airway obstruction. 

PMID- 24084610
TI  - Neonatal seizures: soothing a burning topic.
AB  - Neonatal seizures are a potentially life-threatening pediatric problem with a
      variety of causes, such as birth trauma, asphyxia, congenital anomalies,
      metabolic disturbances, infections, and drug withdrawal or intoxication. Thorough
      and timely evaluations of such patients are necessary to identify and treat the
      underlying etiology, therefore reducing potential morbidity and mortality. We
      review neonatal seizures and hypocalcemia and present the case of a 6-day-old
      male infant who presented to a tertiary pediatric emergency department with
      seizure-like episodes. He was found to have markedly low serum calcium,
      magnesium, and parathyroid hormone concentrations, as well as a significantly
      elevated serum phosphate concentration. The etiology of these abnormalities was
      found to be maternal ingestion of extremely high doses of calcium carbonate
      during the third trimester of her pregnancy, an occurrence that has been reported
      only once in the literature. Education pertaining to the dangers of excessive
      calcium carbonate intake during pregnancy may be an important piece of
      anticipatory guidance for pregnant mothers with symptoms of gastroesophageal
      reflux, and questioning the mother of a neonate presenting with seizures about
      such over-the-counter medications may help to elucidate the diagnosis. 

PMID- 24084611
TI  - Spinal cord avulsion in the pediatric population: case study and review.
AB  - Spinal cord injury without radiographic abnormality (SCIWORA) is a rare
      phenomenon, but with advances in imaging and improvements in magnetic resonance
      imaging more cases are being identified. Even more uncommon is the finding of
      spinal cord avulsion as a type of SCIWORA with only single case reports in the
      literature. We present the case reports of 2 patients both experiencing spinal
      cord avulsion as a type of SCIWORA, secondary to improper lap-belt restraint
      during a motor vehicle accident. 

PMID- 24084612
TI  - A toddler with vomiting, abdominal pain, and alopecia.
AB  - A previously healthy toddler presented to the emergency department with
      nonspecific gastrointestinal complaints. Laboratory studies were consistent with
      pancreatitis, and imaging studies demonstrated a pancreatic transection. Alopecia
      felt to be related to traction was also noted. There was no history of any
      witnessed trauma, and nonaccidental trauma was diagnosed. 

PMID- 24084613
TI  - Rare-earth magnet ingestion: a childhood danger reaches adolescence.
AB  - Ingestion of multiple magnets may cause serious gastrointestinal morbidity, such
      as pressure necrosis, perforation, fistula formation, or intestinal obstruction
      due to forceful attraction across bowel wall. Although the consequences of
      multiple magnet ingestion are well documented in young children, the current
      popularity of small, powerful rare-earth magnets marketed as "desk toys" has
      heightened this safety concern in all pediatric age groups. A recent US Consumer
      Product Safety Commission product-wide warning additionally reports the
      adolescent practice of using toy high-powered, ball-bearing magnets to simulate
      tongue and lip piercings, a behavior that may increase risk of inadvertent
      ingestion. We describe 2 cases of older children (male; aged 10 and 13 years,
      respectively) with unintentional ingestion of multiple rare-earth magnets. Health
      care providers should be alerted to the potential for misuse of these high
      powered, ball-bearing magnets among older children and adolescents. 

PMID- 24084614
TI  - Revised 4-dose vaccine schedule as part of postexposure prophylaxis to prevent
      human rabies.
AB  - There is overwhelming evidence that the 4-dose vaccine schedule as part of
      postexposure prophylaxis to prevent human rabies for previously unvaccinated
      persons, as recommended by the Advisory Committee on Immunization Practices,
      United States in 2009, is safe and effective. When used appropriately with timely
      wound care and administration of human rabies immune globulin, the administration
      of 4 doses of vaccine on days 0, 3, 7, and 14 is likely to induce an
      adequate,long-lasting antibody response that is able to neutralize rabies virus
      and prevent disease in exposed patients. There has been no change in the
      recommended regimen for pre-exposure prophylaxis and for postexposure prophylaxis
      of previously vaccinated persons or for immunosuppressed patients. 

PMID- 24084616
TI  - Pediatric emergency medicine: legal briefs.

PMID- 24084617
TI  - Emergency department bedside ultrasound diagnosis of retinoblastoma in a child.
AB  - A 30-month-old boy presented to a Haitian emergency department with proptosis,
      periorbital edema, and progressive blindness. Bedside ultrasound examination
      revealed bilateral ocular masses with dense calcifications pathognomonic for
      retinoblastoma. This case illustrates the diagnostic utility of bedside
      ultrasound for an advanced case of retinoblastoma in a resource-poor setting.
      Ocular ultrasound technique is also reviewed. 

PMID- 24084618
TI  - ECGs in the ED.

PMID- 24084619
TI  - Use of bicarbonate in the management of diabetic ketoacidosis.

PMID- 24084620
TI  - Response to letter: use of bicarbonate in the management of diabetic
      ketoacidosis.

PMID- 24084621
TI  - Obsessive-compulsive disorder; chronic versus non-chronic symptoms.
AB  - OBJECTIVE: Understanding chronicity in OCD is hampered by contradictory findings
      arising from dissimilar definitions of chronic OCD. The purpose of this study was
      to investigate the magnitude of chronicity in OCD and to examine if chronic OCD
      is critically different from non-chronic OCD, using a chronicity definition that
      reflects empirical findings. METHOD: Baseline data of the Netherlands Obsessive
      Compulsive Disorder Association (NOCDA) study, in which 379 OCD patients
      participated, were analyzed. Chronic OCD was defined as "continuous presence of
      at least moderately severe OCD symptoms during at least two years", and was
      assessed retrospectively using a Life-Chart Interview. RESULTS: Application of
      the chronicity criterion resulted in two groups with highly distinguishable
      course patterns. The majority of the sample (61.7%) reported a chronic course.
      Patients with a chronic course reported significantly more severe OCD symptoms,
      more illness burden, more comorbidity, an earlier OCD onset and more
      contamination and washing - and symmetry and ordering symptoms. Multivariable
      logistic regression analysis revealed that chronic OCD was independently
      associated with more OCD-subtypes (p<0.001), contamination and washing symptoms
      (p<0.001), earlier OCD onset (p=0.05) and higher severity of compulsions (p<.01).
      LIMITATIONS: The findings are based on a cross-sectional survey. Furthermore
      course was assessed retrospectively, implying the possibility of overestimation
      of persistence and severity of symptoms. CONCLUSION: Chronicity is the rule
      rather than the exception in OCD in clinical samples. Chronic OCD is critically
      different from non-chronic OCD. Further attempts to break down the heterogeneity
      of OCD in homogeneous course subtypes should be made to allow for a more precise
      determination of the pathogenesis of OCD and better treatment.

PMID- 24084622
TI  - Self-reported creativity in bipolar disorder: prevalence, types and associated
      outcomes in mania versus hypomania.
AB  - BACKGROUND: Bipolar (BP) disorder has been linked to creativity following
      investigation of prominent artists and controlled trials of creativity in BP
      disorder patients. However, it is unclear whether creativity is differentially
      expressed across the BP I and BP II subtypes. METHODS: 219 patients (aged 19-63
      years) diagnosed with BP disorder by clinical interview and DSM-IV criteria were
      asked whether they tended to be more creative during hypo/manic episodes, and
      answered five questions about personality styles associated with creativity.
      Qualitative analyses were performed on a smaller subset of 69 BP patients (n=19
      BP I, n=50 BP II) who provided written responses of the types of creative
      activities engaged in when hypo/manic and any perceived advantages or
      disadvantages of their creative pursuits. RESULTS: 82% of BP patients affirmed
      being creative when hypo/manic, with comparable results for the BP I and BP II
      subtypes (84% and 81% respectively). Both BP subtypes engaged mostly in writing,
      painting, work or business ideas and 'other' forms of art; however BP II patients
      were more likely to draw and be musical. Both subgroups reported the consequences
      of feeling good, being productive or quitting their project. BP I patients were
      more likely to overspend during their creative highs while BP II patients were
      more likely to experience improved focus and clarity. BP patients affirming
      creative highs were significantly more likely to report creative personality
      styles more generally outside of a mood episode. LIMITATIONS: BP patients' self
      reported creative activities were not retrospectively judged for quality or
      originality and so may reflect common creative abilities rather than exceptional
      quality. The impact of depressive episodes on creativity was not assessed. Uneven
      sample sizes in the BP I and BP II subgroups may have compromised statistical
      power. CONCLUSION: Creativity during hypo/manic episodes was extremely common in
      both BP subtypes. While some nuances in activity type and outcomes were observed,
      no significant creative phenotype specific to BP I or BP II disorder emerged.

PMID- 24084623
TI  - Ancient carbon from a melting glacier gives high 14C age in living pioneer
      invertebrates.
AB  - Glaciers are retreating and predatory invertebrates rapidly colonize deglaciated,
      barren ground. The paradox of establishing predators before plants and herbivores
      has been explained by wind-driven input of invertebrate prey. Here we present an
      alternative explanation and a novel glacier foreland food web by showing that
      pioneer predators eat locally produced midges containing 21,000 years old ancient
      carbon released by the melting glacier. Ancient carbon was assimilated by aquatic
      midge larvae, and terrestrial adults achieved a radiocarbon age of 1040 years.
      Terrestrial spiders, harvestmen and beetles feeding on adult midges had
      radiocarbon ages of 340-1100 years. Water beetles assumed to eat midge larvae
      reached radiocarbon ages of 1100-1200 years. Because both aquatic and terrestrial
      pioneer communities use ancient carbon, the term "primary succession" is
      questionable in glacier forelands. If our "old" invertebrates had been collected
      as subfossils and radiocarbon dated, their age would have been overestimated by
      up to 1100 years. 

PMID- 24084624
TI  - A covalently anchored homogeneous gold complex on carbon nanotubes: a reusable
      catalyst.
AB  - The gold complex [Tf2NAuPPh3CH2NH2] was synthesized and covalently anchored on
      modified carbon nanotubes in order to obtain a supported gold homogeneous
      catalyst. Simple 1,6 enynes were chosen as benchmark substrates to assess its
      behaviour in cyclization catalysis as well as study its recycling. 

PMID- 24084625
TI  - Leukocyte count is a modulating factor for the mortality benefit of bivalirudin
      in ST-segment-elevation acute myocardial infarction: the HORIZONS-AMI trial.
AB  - BACKGROUND: Although the reduction in mortality with bivalirudin compared with
      unfractionated heparin plus glycoprotein IIb/IIIa inhibitors in the Harmonizing
      Outcome with Revascularization and Stent in Acute Myocardial Infarction (HORIZONS
      AMI) trial has been attributed to lower rates of major bleeding, alternative
      mechanisms have not been investigated in depth. We sought to investigate whether
      there might be an interaction between white blood cell (WBC) count and
      bivalirudin for the risk of mortality, and whether this interaction is
      independent of major bleeding. METHODS AND RESULTS: Among the 3602 patients
      enrolled in the HORIZONS-AMI trial, WBC count was available in 3433 (95.3%)
      patients. Patients were stratified according to WBC tertiles. At 1-year follow
      up, bivalirudin was associated with significantly lower rates of mortality and
      cardiac mortality compared with unfractionated heparin plus glycoprotein IIb/IIIa
      inhibitors in patients in the upper WBC tertile (all-cause death: 4.1% versus
      9.3%, respectively; P=0.0004; cardiac death: 2.0% versus 6.9%; respectively;
      P<0.0001) but not in patients in the mid-WBC or lower WBC tertiles. The reduction
      of mortality with bivalirudin across WBC tertiles was independent of major
      bleeding, and a significant interaction was apparent for 1-year all-cause
      mortality and cardiac mortality between WBC and bivalirudin therapy. Similar
      findings were apparent at 3 years. CONCLUSIONS: In patients with ST-segment
      elevation myocardial infarction, a significant interaction between bivalirudin
      therapy and admission WBC count was apparent for 1-year mortality. The reduction
      in mortality was independent of major bleeding, suggesting that other mechanisms
      may be implicated in the survival benefit observed with bivalirudin. CLINICAL
      TRIAL REGISTRATION URL: http://www.clinicaltrials.gov. Unique identifier:
      NCT00433966.

PMID- 24084626
TI  - Intralesional abciximab and thrombus aspiration in patients with large anterior
      myocardial infarction: one-year results from the INFUSE-AMI trial.
AB  - BACKGROUND: Whether intralesional abciximab administration and thrombus
      aspiration confer clinical benefits to patients undergoing primary percutaneous
      coronary intervention for ST-segment-elevation myocardial infarction is
      controversial. METHODS AND RESULTS: A total of 452 patients with ST-segment
      elevation myocardial infarction caused by proximal or mid left anterior
      descending artery occlusion undergoing primary percutaneous coronary intervention
      with bivalirudin anticoagulation were randomized in a 2*2 factorial design to
      bolus abciximab delivered locally at the infarct lesion site versus no abciximab
      and to manual thrombus aspiration versus no aspiration. Treatment with
      intralesional abciximab, thrombus aspiration, or both therapies compared with no
      active therapy before stent implantation resulted in lower 1-year rates of death
      (4.5% versus 10.4%; P=0.03), severe heart failure (4.2% versus 10.3%; P=0.02),
      and stent thrombosis (0.9% versus 3.8%; P=0.046). Between 30 days and 1 year of
      follow-up, treatment with intralesional abciximab compared with no abciximab was
      associated with a lower rate of death (1.4% versus 4.9%; P=0.04) and composite
      major adverse ischemic events (3.3% versus 7.8%; P=0.04), with nonsignificantly
      different overall 1-year rates of mortality, composite ischemic events, and heart
      failure-related events. Thrombus aspiration compared with no aspiration was
      associated with lower rates of new-onset severe heart failure between 30 days and
      1 year (0.9% versus 4.5%; P=0.02) and of rehospitalization for heart failure from
      randomization to 1 year (0.9% versus 5.4%; P=0.0008), with nonsignificantly
      different rates of mortality. CONCLUSIONS: Intralesional abciximab and thrombus
      aspiration may have long-term benefits in patients with anterior ST-segment
      elevation myocardial infarction presenting early after symptom onset and
      undergoing primary percutaneous coronary intervention with bivalirudin
      anticoagulation. CLINICAL TRIAL REGISTRATION URL: http://www.clinicaltrials.gov.
      Unique identifier: NCT00976521.

PMID- 24084627
TI  - Flow reversal versus filter protection: a pilot carotid artery stenting
      randomized trial.
AB  - BACKGROUND: Carotid artery stenting (CAS) has become an alternative treatment for
      patients presenting symptomatic carotid artery stenosis. The improvement in
      clinical outcomes with CAS has been associated with the development of embolic
      protection devices. The trial aim is to compare flow reversal versus filter
      protection during CAS through femoral access. METHODS AND RESULTS: Patients were
      randomly enrolled in CAS using flow reversal or filter protection. The primary
      end points were the incidence, number, and size of new ischemic brain lesions
      after CAS. The secondary end points included major adverse cardiac and
      cerebrovascular events, transient ischemic attack, and definitive ischemic brain
      lesions on fluid-attenuated inversion recovery magnetic resonance image at a 3
      month follow-up. Ischemic brain lesions were assessed by a 3T magnetic resonance
      image. Neurological outcomes were evaluated by means of the National Institutes
      of Health Stroke Scale and the modified Rankin Scale (mRS). Forty consecutive
      patients were randomly assigned. Compared with flow reversal (n=21), filter
      protection (n=19) resulted in a significant reduction in the incidence (15.8%
      versus 47.6%, P=0.03), number (0.73 versus 2.6, P=0.05), and size (0.81 versus
      2.23 mm, P=0.05) of new ischemic brain lesions. Two patients, 1 from each group,
      presented transient ischemic attack at 3-month follow-up. There were no major
      adverse cardiac and cerebrovascular events in the hospital or at 3-month follow
      up. CONCLUSIONS: In this small sample size trial, filter protection was more
      effective than flow reversal in reducing ischemic brain lesions during CAS
      through femoral approach. CLINICAL TRIAL REGISTRATION URL:
      http://portal2.saude.gov.br/sisnep/. Unique identifier: 0538.0.004.000-10.

PMID- 24084628
TI  - Pinar T. Ozand: Clinician-Scientist Extraordinaire.

PMID- 24084629
TI  - Carpal tunnel syndrome in children.
AB  - Carpal tunnel syndrome rarely occurs in children. We retrospectively analyzed
      clinical data of 11 patients aged 5-17 diagnosed with carpal tunnel syndrome at a
      single pediatric neuromuscular center. Nerve conduction studies were performed
      according to the American Association of Electrodiagnostic Medicine
      recommendations. Additional imaging tests of the wrist were performed in 10
      patients. In our group of 11 children, carpal tunnel syndrome was idiopathic in
      only 1 case. In the remaining subjects, it was secondary to congenital bone
      anomaly (6), hypothyroidism (2), or myopathic contractures (1). In 1 case,
      metabolic workup revealed an underlying mucopolysaccharidosis. Our results
      confirm that idiopathic carpal tunnel syndrome is rare in children. Hand
      clumsiness and thenar hypoplasia rather than sensory complaints are the
      presenting symptoms. Whenever carpal tunnel syndrome is diagnosed in a child, a
      thorough differential diagnosis should be made because of the secondary nature of
      this disease in most pediatric patients. 

PMID- 24084630
TI  - A cost-minimization analysis of an RCT of three retention methods.
AB  - BACKGROUND: There are few cost evaluation studies of orthodontic retention
      treatment. The aim of this study was to compare the costs in a randomized
      controlled trial of three retention methods during 2 years of retention
      treatment. MATERIALS/METHODS: To determine which alternative has the lower cost,
      a cost-minimization analysis (CMA) was undertaken, based on that the outcome of
      the treatment alternatives was equivalent. The study comprised 75 patients in 3
      groups consisting of 25 each. The first group had a vacuum-formed retainer (VFR)
      in the maxilla and a cuspid retainer in the mandible (group V-CTC), the second
      group had a VFR in the maxilla combined with stripping of the incisors and
      cuspids in the mandible (group V-S), and the third group had a prefabricated
      positioner (group P). Direct cost (premises, staff salaries, material and
      laboratory costs) and indirect costs (loss of time at school) were calculated.
      Societal costs were defined as the sum of direct and indirect costs. RESULTS: The
      societal costs/patient for scheduled appointments for 2 years of retention
      treatment in group V-CTC were ?497, group V-S ?451 and group P ?420. Societal
      costs for unscheduled appointments in group V-CTC were ?807 and in group V-S
      ?303. In group P, there were no unscheduled appointments.
      CONCLUSIONS/IMPLICATIONS: After 2 years of retention in compliant patients, the
      cuspid retainer was the least cost-effective retention appliance. The CMA showed
      that for a clinically similar result, there were differences in societal costs,
      but treatment decisions should always be performed on an individual basis.

PMID- 24084632
TI  - Efficient energy transfer in a new hybrid diphenylfluorene derivative-CdS quantum
      dot nanocomposite.
AB  - We report the synthesis of a novel compound, 9,9-bis(3'-aminopropyl)-2,7
      diphenylfluorene (BAPDPF), and a new approach to graft the BAPDPF onto a CdS
      quantum dot (QD) surface via an acylation reaction. FT-IR and TGA
      characterizations indicate the formation of robust bonding between BAPDPF and
      QDs; the structures of the bare QDs and BAPDPF-CdS QD hybrid nanocomposites
      estimated by transmission electron microscopy (TEM) showed that they have the
      same size of about 3.5 nm. The extent of the spectral overlap between the
      emission of BAPDPF and absorption of QDs, and the change of fluorescence emission
      for the organic and inorganic components of the hybrid, demonstrate that the
      energy transfer process occurs from BAPDPF to the CdS QDs. The energy transfer of
      about 44% efficiency is corroborated by time-resolved fluorescence measurements,
      and then the solid-state photoluminescence quantum yield (PLQY) of the
      nanocomposite is measured using an integrating sphere and a conventional
      fluorimeter. Because of the fact that the PLQY of the nanocomposite is 9.1 times
      larger than that of the pristine QDs, due to the energy transfer between the
      donor and the acceptor and passivation effects on the surface of the acceptor,
      the presented BAPDPF-CdS QD hybrid nanocomposites are potentially interesting in
      nanoparticle-based light-emitting devices. 

PMID- 24084633
TI  - Improving end-of-life care for patients with chronic obstructive pulmonary
      disease.
AB  - The provision and awareness of the need for end-of-life care has expanded greatly
      in the past decade. The burgeoning older adult population is obviously a factor
      in the growth of both hospice and palliative care organizations. Additionally,
      public awareness and healthcare literacy campaigns have called attention to the
      plight of those dying in pain. Healthcare professionals have stepped up their
      initiatives to educate both the patient and family members about the options
      available to them at the end of life, however many patients with chronic
      obstructive lung disease (COPD) still do not receive adequate palliation of
      symptoms. This article will highlight some of the issues related to end-of-life
      care for individuals diagnosed with COPD and offer suggestions on how better care
      can be implemented. 

PMID- 24084631
TI  - Angiotensin inhibition enhances drug delivery and potentiates chemotherapy by
      decompressing tumour blood vessels.
AB  - Cancer and stromal cells actively exert physical forces (solid stress) to
      compress tumour blood vessels, thus reducing vascular perfusion. Tumour
      interstitial matrix also contributes to solid stress, with hyaluronan implicated
      as the primary matrix molecule responsible for vessel compression because of its
      swelling behaviour. Here we show, unexpectedly, that hyaluronan compresses
      vessels only in collagen-rich tumours, suggesting that collagen and hyaluronan
      together are critical targets for decompressing tumour vessels. We demonstrate
      that the angiotensin inhibitor losartan reduces stromal collagen and hyaluronan
      production, associated with decreased expression of profibrotic signals TGF
      beta1, CCN2 and ET-1, downstream of angiotensin-II-receptor-1 inhibition.
      Consequently, losartan reduces solid stress in tumours resulting in increased
      vascular perfusion. Through this physical mechanism, losartan improves drug and
      oxygen delivery to tumours, thereby potentiating chemotherapy and reducing
      hypoxia in breast and pancreatic cancer models. Thus, angiotensin inhibitors 
      inexpensive drugs with decades of safe use - could be rapidly repurposed as
      cancer therapeutics. 

PMID- 24084634
TI  - Imaging centrosomes in fly testes.
AB  - Centrosomes are conserved microtubule-based organelles whose structure and
      function change dramatically throughout the cell cycle and cell differentiation.
      Centrosomes are essential to determine the cell division axis during mitosis and
      to nucleate cilia during interphase. The identity of the proteins that mediate
      these dynamic changes remains only partially known, and the function of many of
      the proteins that have been implicated in these processes is still rudimentary.
      Recent work has shown that Drosophila spermatogenesis provides a powerful system
      to identify new proteins critical for centrosome function and formation as well
      as to gain insight into the particular function of known players in centrosome
      related processes. Drosophila is an established genetic model organism where
      mutants in centrosomal genes can be readily obtained and easily analyzed.
      Furthermore, recent advances in the sensitivity and resolution of light
      microscopy and the development of robust genetically tagged centrosomal markers
      have transformed the ability to use Drosophila testes as a simple and accessible
      model system to study centrosomes. This paper describes the use of genetically
      tagged centrosomal markers to perform genetic screens for new centrosomal mutants
      and to gain insight into the specific function of newly identified genes. 

PMID- 24084635
TI  - Refolding of the recombinant protein Sm29, a step toward the production of the
      vaccine candidate against schistosomiasis.
AB  - Schistosomiasis is an important parasitic disease, with about 240 million people
      infected worldwide. Humans and animals can be infected, imposing an enormous
      social and economic burden. The only drug available for chemotherapy,
      praziquantel, does not control reinfections, and an efficient vaccine for
      prophylaxis is still missing. However, the tegumental protein Sm29 of Schistosoma
      mansoni was shown to be a promising antigen to compose an anti-schistosomiasis
      vaccine. Though, recombinant Sm29 is expressed in Escherichia coli as insoluble
      inclusion bodies requiring an efficient process of refolding, thus, hampering its
      production in large scale. We present in this work studies to refold the
      recombinant Sm29 using high hydrostatic pressure, a mild condition to dissociate
      aggregated proteins, leading to refolding on a soluble conformation. Our studies
      resulted in high yield of rSm29 (73%) as a stably soluble and structured protein.
      The refolded antigen presented protective effect against S. mansoni development
      in immunized mice. We concluded that the refolding process by application of high
      hydrostatic pressure succeeded, and the procedure can be scaled-up, allowing
      industrial production of Sm29.

PMID- 24084636
TI  - Identification of factors influencing the pharmacokinetics of voriconazole and
      the optimization of dosage regimens based on Monte Carlo simulation in patients
      with invasive fungal infections.
AB  - OBJECTIVES: The objective of this study was to estimate the population
      pharmacokinetics of voriconazole, to identify the factors influencing
      voriconazole pharmacokinetics and to identify optimal dosage regimens for
      attaining target pharmacokinetic/pharmacodynamic indices against Aspergillus and
      Candida infections in patients with invasive fungal infections (IFIs). METHODS:
      To prospectively quantify the relationships between the pharmacokinetic
      parameters of voriconazole and covariates, a population pharmacokinetic analysis
      was conducted on pooled data from 406 samples taken from 151 patients with IFIs.
      Voriconazole plasma concentrations were measured by HPLC. The following
      covariates were tested: demographic factors, laboratory data, concomitant
      medications and CYP2C19 genotype. Monte Carlo simulation was used to evaluate the
      effectiveness of the currently recommended dosage regimen and to design an
      optimized pharmacodynamic dosage strategy for voriconazole. RESULTS: The data
      were appropriately fit by a one-compartment model with first-order absorption and
      elimination. The voriconazole clearance (CL) was 6.95 L/h, the volume of
      distribution (V) was 200 L and the oral bioavailability (F) was 89.5%. CL was
      significantly associated with age, the serum concentration of alkaline
      phosphatase and the CYP2C19 genotype. Based on the results of the Monte Carlo
      stimulation, we concluded that Aspergillus infections could be treated
      effectively with 200 mg of voriconazole administered intravenously or orally
      twice daily and that Candida infections could be treated with 300 mg administered
      orally twice daily or with 200 mg administered intravenously twice daily.
      CONCLUSIONS: This study showed that optimal voriconazole dosage regimens could be
      determined successfully with prospective population pharmacokinetic analyses and
      Monte Carlo simulations.

PMID- 24084638
TI  - Complete sequence of a multiresistance plasmid from a methicillin-resistant
      Staphylococcus epidermidis ST5 isolated in a small animal clinic.

PMID- 24084637
TI  - Target optimization for peptide nucleic acid (PNA)-mediated antisense inhibition
      of the CmeABC multidrug efflux pump in Campylobacter jejuni.
AB  - OBJECTIVES: CmeABC is a resistance-nodulation-cell division (RND)-type multidrug
      efflux pump conferring resistance to clinically important antibiotics in
      Campylobacter. This study aimed to identify the optimal target sites for the
      inhibition of CmeABC with antisense peptide nucleic acid (PNA). METHODS: Eighteen
      PNAs were designed to bind to the translational initiation regions of cmeABC,
      spanning the ribosome-binding site (RBS) and the start codon of the cmeABC genes.
      Campylobacter jejuni was treated with CmeABC-specific PNAs (CmeABC-PNAs) at
      various concentrations and subjected to western blotting to measure changes in
      the level of CmeABC expression. The MICs of ciprofloxacin and erythromycin were
      measured to evaluate the impact of CmeABC knockdown on antibiotic susceptibility.
      RESULTS: While antisense PNA significantly affected CmeA and CmeB expression,
      interestingly, CmeC expression was not altered by any of the CmeC-PNAs used in
      this study. A CmeA-PNA targeting the RBS of cmeA and its upstream region reduced
      CmeA expression most efficiently, and CmeB expression was most significantly
      decreased by PNA binding to the RBS of cmeB and its downstream region. CmeA- and
      CmeB-PNAs increased the susceptibility of C. jejuni to ciprofloxacin and
      erythromycin in proportion to the inhibition levels observed in western blotting.
      CONCLUSIONS: The cmeA gene is the best target to knockdown CmeABC with antisense
      PNA. The RBS is the major target for the PNA-mediated antisense inhibition of
      CmeABC. However, regions in its vicinity also significantly influence the
      effectiveness of the PNA-based knockdown of CmeABC.

PMID- 24084639
TI  - Azole-resistant Aspergillus fumigatus with the environmental TR46/Y121F/T289A
      mutation in India.

PMID- 24084640
TI  - Risk factors for increased antimicrobial resistance: a retrospective analysis of
      309 acute cholangitis episodes.
AB  - OBJECTIVES: To assess the risk factors for increased antimicrobial resistance
      among Enterobacteriaceae representing the most common biliary pathogens. METHODS:
      A retrospective analysis was conducted of 276 patients with acute cholangitis
      treated at a German tertiary centre between April 1996 and May 2009. The
      resistance patterns among Enterobacteriaceae isolated from blood/bile cultures
      were compared and related to age, sex, the genesis of the cholangitis and the
      type and number of previous interventional procedures [percutaneous transhepatic
      cholangiography (PTC)/endoscopic retrograde cholangiography (ERC)]. Univariate
      and multivariate generalized estimation equation models were used to compute ORs
      with corresponding 95% CIs for the binomial outcomes. RESULTS: According to the
      univariate analysis, patients undergoing stent therapy had a smaller proportion
      of Enterobacteriaceae with susceptibility to quinolones (ofloxacin/ciprofloxacin)
      (184/239 versus 205/221; P < 0.001) and to ceftriaxone (208/239 versus 209/222; P
      = 0.014). Logistic regression analysis revealed that the odds for acquiring
      ceftriaxone-resistant Enterobacteriaceae were 4-fold higher than in patients who
      had not undergone stent therapy (P = 0.039). Furthermore, an increased number of
      interventional procedures (PTC/ERC) was associated with lower susceptibility. The
      odds for susceptibility to ampicillin, ampicillin/sulbactam, ceftriaxone,
      quinolones and co-trimoxazole decreased by 2%, 2%, 4%, 6% and 3%, respectively,
      per interventional procedure. Age, sex and type of interventional procedure
      displayed no significant relationship to the development of antimicrobial
      resistance. CONCLUSIONS: Stent therapy was found to be a risk factor for
      increased antimicrobial resistance in patients with acute cholangitis,
      particularly those who had undergone numerous interventional procedures prior to
      the onset of the cholangitis.

PMID- 24084641
TI  - Appropriate international measures for outpatient antibiotic prescribing and
      consumption: recommendations from a national data comparison of different
      measures.
AB  - OBJECTIVES: Many European countries have engaged in awareness campaigns to
      decrease outpatient antibiotic use and several measures have been proposed, e.g.
      the number of defined daily doses (DDDs) or packages per 1000 inhabitants per
      day, producing conflicting findings. Therefore, we set out to explore what
      measure is most appropriate. METHODS: Outpatient data on each dispensed and
      reimbursed medicinal package in Belgium between 2002 and 2009 were aggregated at
      the level of the active substance in accordance with the Anatomical Therapeutic
      Chemical classification and expressed as the numbers of DDDs (WHO, version 2010),
      packages, treatments and insured individuals per 1000 inhabitants, insured
      individuals and patient contacts, per day, and in July-June years. Using these
      measures, time trends of outpatient antibiotic use were compared and explored in
      detail. RESULTS: Expressed per 1000 inhabitants per day, outpatient antibiotic
      use increased between 2002-03 and 2008-09 in DDDs, whereas in packages,
      treatments and insured individuals it decreased. The same was true for use
      expressed per 1000 insured individuals or when allowing for the decreasing number
      of patient contacts. Increasing numbers of DDDs per package (more items per
      package and higher doses per unit for amoxicillin and co-amoxiclav) explain these
      discrepancies. CONCLUSIONS: The number of packages is a more appropriate measure
      than the number of DDDs when assessing outpatient antibiotic use over time and
      the impact of awareness campaigns in countries dispensing 'complete packages'. We
      recommended the use of different complementary measures or caution when
      interpreting trends based only on DDDs.

PMID- 24084642
TI  - Laser capture microdissection of neurons from differentiated human
      neuroprogenitor cells in culture.
AB  - Neuroprogenitor cells (NPCs) isolated from the human fetal brain were expanded
      under proliferative conditions in the presence of epidermal growth factor (EGF)
      and fibroblast growth factor (FGF) to provide an abundant supply of cells. NPCs
      were differentiated in the presence of a new combination of nerve growth factor
      (NGF), brain-derived neurotrophic factor (BDNF), dibutyryl cAMP (DBC) and
      retinoic acid on dishes coated with poly-L-lysine and mouse laminin to obtain
      neuron-rich cultures. NPCs were also differentiated in the absence of
      neurotrophins, DBC and retinoic acid and in the presence of ciliary neurotrophic
      factor (CNTF) to yield astrocyte-rich cultures. Differentiated NPCs were
      characterized by immunofluorescence staining for a panel of neuronal markers
      including NeuN, synapsin, acetylcholinesterase, synaptophysin and GAP43. Glial
      fibrillary acidic protein (GFAP) and STAT3, astrocyte markers, were detected in
      10-15% of differentiated NPCs. To facilitate cell-type specific molecular
      characterization, laser capture microdissection was performed to isolate neurons
      cultured on polyethylene naphthalate (PEN) membrane slides. The methods described
      in this study provide valuable tools to advance our understanding of the
      molecular mechanism of neurodegeneration. 

PMID- 24084643
TI  - Deciphering the fine-structure of tribal admixture in the Bedouin population
      using genomic data.
AB  - The Bedouin Israeli population is highly inbred and structured with a very high
      prevalence of recessive diseases. Many studies in the past two decades focused on
      linkage analysis in large, multiple consanguineous pedigrees of this population.
      The advent of high-throughput technologies motivated researchers to search for
      rare variants shared between smaller pedigrees, integrating data from clinically
      similar yet seemingly non-related sporadic cases. However, such analyses are
      challenging because, without pedigree data, there is no prior knowledge regarding
      possible relatedness between the sporadic cases. Here, we describe models and
      techniques for the study of relationships between pedigrees and use them for the
      inference of tribal co-ancestry, delineating the complex social interactions
      between different tribes in the Negev Bedouins of southern Israel. Through our
      analysis, we differentiate between tribes that share many yet small genomic
      segments because of co-ancestry versus tribes that share larger segments because
      of recent admixture. The emergent pattern is well correlated with the prevalence
      of rare mutations in the different tribes. Tribes that do not intermarry, mostly
      because of social restrictions, hold private mutations, whereas tribes that do
      intermarry demonstrate a genetic flow of mutations between them. Thus, social
      structure within an inbred community can be delineated through genomic data, with
      implications to genetic counseling and genetic mapping.

PMID- 24084644
TI  - Extremely reduced dispersal and gene flow in an island bird.
AB  - The Reunion grey white-eye, Zosterops borbonicus, a passerine bird endemic to
      Reunion Island in the Mascarene archipelago, represents an extreme case of
      microgeographical plumage colour variation in birds, with four distinct colour
      forms occupying different parts of this small island (2512 km(2)). To understand
      whether such population differentiation may reflect low levels of dispersal and
      gene flow at a very small spatial scale, we examined population structure and
      gene flow by analysing variation at 11 microsatellite loci among four
      geographically close localities (<26 km apart) sampled within the distribution
      range of one of the colour forms, the brown-headed brown form. Our results
      revealed levels of genetic differentiation that are exceptionally high for birds
      at such a small spatial scale. This strong population structure appears to
      reflect low levels of historical and contemporary gene flow among populations,
      unless very close geographically (<10 km). Thus, we suggest that the Reunion grey
      white-eye shows an extremely reduced propensity to disperse, which is likely to
      be related to behavioural processes.

PMID- 24084645
TI  - A conserved extraordinarily long serine homopolymer in Dictyostelid amoebae.
AB  - Eukaryotic protein sequences often contain amino-acid homopolymers that consist
      of a single amino acid repeated from several to dozens of times. Some of these
      are functional but others may persist largely because of high expansion rates due
      to DNA slippage. However, very long homopolymers with over a hundred repeats are
      very rare. We report an extraordinarily long homopolymer consisting of 306 tandem
      serine repeats from the single-celled eukaryote Dictyostelium discoideum, which
      also has a multicellular stage. The gene has a paralog with 132 repeats and
      orthologs, also with high serine repeat numbers, in various other Dictyostelid
      species. The conserved gene structure and protein sequences suggest that the
      homopolymer is functional. The high codon diversity and very poor alignment of
      serine codons in this gene between species similarly indicate functionality. This
      is because the serine homopolymer is conserved despite much DNA sequence change.
      A survey of other very long amino-acid homopolymers in eukaryotes shows that high
      codon diversity is the rule, suggesting that these too may be functional.

PMID- 24084647
TI  - Helping without harming: the instructor's feedback dilemma in debriefing--a case
      study.
AB  - INTRODUCTION: Simulation instructors often feel caught in a task-versus
      relationship dilemma. They must offer clear feedback on learners' task
      performance without damaging their relationship with those learners, especially
      in formative simulation settings. Mastering the skills to resolve this dilemma is
      crucial for simulation faculty development. METHODS: We conducted a case study of
      a debriefer stuck in this task-versus-relationship dilemma. DATA: The "2-column
      case" captures debriefing dialogue and instructor's thoughts and feelings or the
      "subjective experience." ANALYSIS: The "learning pathways grid" guides a peer
      group of faculty in a step-by-step, retrospective analysis of the debriefing. The
      method uses vivid language to highlight the debriefer's dilemmas and how to
      surmount them. RESULTS: The instructor's initial approach to managing the task
      versus-relationship dilemma included (1) assuming that honest critiques will
      damage learners, (2) using vague descriptions of learner actions paired with
      guess-what-I-am-thinking questions, and (3) creating a context she worried would
      leave learners feeling neither safe nor clear how they could improve. This case
      study analysis identified things the instructor could do to be more effective
      including (1) making generous inferences about the learners' qualities, (2)
      normalizing the challenges posed by the simulation, (3) assuming there are
      different understandings of what it means to be a team. CONCLUSIONS: There are
      key assumptions and ways of interacting that help instructors resolve the task
      versus-relationship dilemma. The instructor can then provide honest feedback in a
      rigorous yet empathic way to help sustain good or improve suboptimal performance
      in the future.

PMID- 24084646
TI  - Regulation of growth by the trehalose pathway: relationship to temperature and
      sucrose.
AB  - Carbon signaling can override carbon supply in the regulation of growth. At least
      some of this regulation is imparted by the sugar signal trehalose 6-phosphate
      (T6P) through the protein kinase, SnRK1. This signaling pathway regulates
      biosynthetic processes involved in growth under optimal growing conditions.
      Recently, using a seedling system we showed that under sub-optimal conditions,
      such as cold, carbon signaling by T6P/ SnRK1 enables recovery of growth following
      relief of the stress. The T6P/ SnRK1 mechanism thus could be selected as a means
      of improving low temperature tolerance. High-throughput automated Fv/Fm
      measurements provide a potential means to screen for T6P/ SnRK1, and here we
      confirm through measurements of Fv/Fm in rosettes that T6P promotes low
      temperature tolerance and recovery during cold to warm transfer. Further, to
      better understand the coordination between sugars, trehalose pathway, and
      temperature-dependent growth, we examine the interrelationship between sugars,
      trehalose phosphate synthase (TPS), and trehalose phosphate phosphatase (TPP)
      gene expression and T6P content in seedlings. Sucrose, particularly when fed
      exogenously, correlated well with TPS1 and TPPB gene expression, suggesting that
      these enzymes are involved in maintaining carbon flux through the pathway in
      relation to sucrose supply. However, when sucrose accumulated to higher levels
      under low temperature and low N, TPS1 and TPPB expression were less directly
      related to sucrose; other factors may also contribute to regulation of TPS1 and
      TPPB expression under these conditions. TPPA expression was not related to
      sucrose content and all genes were not well correlated with endogenous glucose.
      Our work has implications for understanding acclimation to sink-limited growth
      conditions such as low temperature and for screening cold-tolerant genotypes with
      altered T6P/ SnRK1 signaling.

PMID- 24084648
TI  - Depletion of the 26S proteasome adaptor Ecm29 increases Toll-like receptor 3
      signaling.
AB  - Toll-like receptor 3 (TLR3) recognizes viral double-stranded RNA and stimulates
      the innate immune response. We found that depletion of extracellular mutant 29
      (Ecm29), an adaptor protein that binds to a subset of 26S proteasomes (Ecm
      proteasomes), increased the abundance of TLR3 in human embryonic kidney-293 and
      HeLa cells. Loss of Ecm29 also increased the amounts of LC3beta and p62, two
      proteins that mediate autophagy. The absence of Ecm29 enhanced TLR3 signaling,
      which was characterized by the increased abundance of the adaptor protein and E3
      ubiquitin ligase tumor necrosis factor receptor-associated factor 3, increased
      phosphorylation and activation of effector kinases downstream of TLR3, increased
      nuclear localization of the transcription factor interferon regulatory factor 3,
      and the accumulation of signaling molecules at juxtanuclear recycling endosomes.
      We conclude that Ecm proteasomes play a previously uncharacterized role in
      mediating autophagy, trafficking of TLR3, and attenuation of TLR3-dependent
      signaling.

PMID- 24084650
TI  - PEG-functionalized microparticles selectively target inflamed mucosa in
      inflammatory bowel disease.
AB  - INTRODUCTION: The systemic therapy of inflammatory bowel diseases (IBD) by oral
      administration of anti-inflammatory and immunosuppressive agents is characterized
      by an increased probability of adverse drug reactions. A successful treatment
      with a simultaneous reduction in adverse events may be achieved by the
      administration of micro- and nanosized targeted drug delivery systems, which
      accumulate selectively in inflamed mucosal areas without systemic absorption. We
      described in a first in vivo study in IBD patients a significantly enhanced, but
      minor accumulation of non-functionalized poly(lactic-co-glycolic acid) (PLGA)
      microparticles in ulcerous lesions very recently. AIM: The aim of this study was
      therefore the assessment of an increased targeting potential of different non-,
      chitosan- and polyethylene glycol (PEG)-functionalized PLGA micro- and
      nanoparticles to inflamed intestinal mucosa compared to healthy mucosa. MATERIALS
      AND METHODS: For the quantification of nano- and microparticles, fluoresceinamine
      labeled-PLGA was synthesized by carbodiimide reaction. Fluorescent chitosan-, PEG
      , and non-functionalized PLGA micro- and nanoparticles with mean hydrodynamic
      diameters of 3000 nm and 300 nm were prepared by solvent evaporation technique.
      The targeting efficiencies in terms of particle translocation and deposition were
      investigated in Ussing chamber experiments. Healthy and inflamed macrobiopsies
      were received from routine endoscopic examinations of patients with IBD as well
      as control patients. RESULTS: One-hundred and one Ussing chamber experiments of
      patients with IBD (Crohn's disease: n=7 and ulcerative colitis: n=9) as well as
      healthy control patients (n=5) were performed. Histomorphological and
      electrophysiological investigations of inflamed mucosal tissues confirmed a
      significant alteration of mucosal barrier integrity in IBD patients (TER:
      healthy: 34.1 Omega cm(2); inflamed: 21.6 Omegac m(2); p=0.034). In summary,
      nanoparticles showed an increased translocation and deposition compared to
      microparticles in healthy and in inflamed mucosa. Chitosan-functionalized
      particles adhered onto the tissue surface and thus showed the lowest particle
      translocation and deposition in healthy and inflamed tissues. PEG-functionalized
      nanoparticles showed the highest translocation through healthy (2.31%) and
      inflamed mucosa (5.27%). Moreover, PEG-functionalized microparticles showed a
      significantly increased translocation through inflamed mucosa (3.33%) compared to
      healthy mucosa (0.55%; p=0.045). Notably, the particle deposition of PEG
      functionalized microparticles was significantly increased in inflamed mucosa
      (10.8%) compared to healthy mucosa (4.1%; p=0.041). CONCLUSIONS: Based on the
      targeted translocation and deposition to inflamed intestinal mucosa, PEG
      functionalized PLGA microparticles were qualified as an innovative drug delivery
      system. These particles may serve as a selective treatment strategy to inflamed
      mucosal areas in IBD with the potential to improve therapeutic efficacy and to
      reduce adverse events.

PMID- 24084651
TI  - Nitrate does not compete with abscisic acid as a substrate of
      AtNPF4.6/NRT1.2/AIT1 in Arabidopsis.
AB  - We identified a member of the Arabidopsis NRT1/PTR FAMILY (NPF), AtNPF4.6, as an
      abscisic acid (ABA) transporter, AIT1. AtNPF4.6 was originally characterized as a
      low-affinity nitrate transporter NRT1.2. We hypothesized that the competition
      between nitrate and ABA as substrates for AtNPF4.6 might be involved in the
      interactions between nitrate and ABA signaling. However, the ABA transport
      activity of AtNPF4.6 was not inhibited by an excess amount of nitrate. In
      addition, the npf4.6 mutant was less sensitive to ABA than the wild type during
      germination irrespective of nitrate concentrations in the media. Furthermore,
      nitrate promoted germination of both wild type and npf4.6 in the presence of ABA.
      These results do not support the idea of a physiological linkage between nitrate
      and ABA signals through AtNPF4.6.

PMID- 24084649
TI  - The TNF family member 4-1BBL sustains inflammation by interacting with TLR
      signaling components during late-phase activation.
AB  - Activation of Toll-like receptor (TLR)-dependent signaling leads to the
      expression of genes encoding proinflammatory factors, such as tumor necrosis
      factor-alpha (TNF-alpha), and this proinflammatory gene expression is sustained
      for the duration of the inflammatory response. TLR4-mediated inflammation, which
      occurs in two phases, depends on the TNF family member 4-1BB ligand (4-1BBL) to
      sustain TNF-alpha production during late-phase signaling. We showed that Toll
      interleukin-1 receptor (TIR) domain-containing adaptor protein (TIRAP) and the
      kinase IRAK2 interacted with 4-1BBL to mediate late-phase TLR4 signaling.
      Expression of 4-1bbl depended on early TLR4 signaling that also induced Tnf
      expression, and 4-1BBL translocated to the plasma membrane, where it interacted
      with TLR4 to mediate late-phase signaling. TLR4-4-1BBL-mediated signaling
      depended on TIRAP and IRAK2, as well as a complex consisting of the E3 ubiquitin
      ligase TRAF6 (TNF receptor-associated factor 6), the kinase TAK1 (transforming
      growth factor-beta-activated kinase 1), and the adaptor protein TAB1 (TAK-binding
      protein 1). Inhibition of this late-phase pathway reduced the extent of TNF-alpha
      production by mouse macrophages exposed to the TLR4 ligand lipopolysaccharide
      (LPS) and ameliorated LPS-induced sepsis in mice. Together, these data suggest
      that TIRAP and IRAK2 are critical for the sustained inflammatory response that is
      mediated by late-phase signaling by the TLR-4-1BBL complex.

PMID- 24084652
TI  - Solid-extracellular fluid interaction and damage in the mechanical response of
      rat brain tissue under confined compression.
AB  - The mechanical processes that underlie mild traumatic brain injury from physical
      insults are not well understood. One aspect in particular that has not been
      examined is the tissue fluid, which is known to be critical in the mechanical
      function of other organs. To investigate the contributions of solid-fluid
      interactions to brain tissue mechanics, we performed confined compression tests,
      that force the extracellular fluid (ECF) to flow in the direction of the
      deformation, on 6.35mm diameter, 3mm long cylindrical samples excised from
      various regions of rat brains. Two types of tests in deformation control, (1)
      quasi-static, slow and moderate constant strain rate tests at 0.64*10(-5)/s,
      0.001/s and 1/s to large strains and (2) several applications of slow linear
      deformation to 5% strain each followed by stress relaxation are employed to
      explore the solid-fluid interaction. At slow and moderate compressive strain
      rates, we observed stress peaks in the applied strain range at about 11%, whose
      magnitudes exhibited statistically significant dependence on strain rate. These
      data suggest that the ECF carries load until the tissue is sufficiently damaged
      to permit pathological fluid flow. Under the slow ramp rate in the ramp
      relaxation cycles protocol, commonly used to estimate permeability, the stress
      relaxes to zero after the first cycle, rather than to a non-zero equilibrium
      stress corresponding to the applied strain, which further implicates mechanical
      damage. Magnetic resonance imaging (MRI) of changes in tissue microstructure
      during confined compression, before and after compression, provides further
      evidence of tissue damage. The solid-fluid interactions, reflected in the
      morphology of the stress-stretch curves and supported by the MRI data, suggest
      that increases in hydrostatic pressure in the ECF may contribute to mechanical
      damage of brain tissue. 

PMID- 24084653
TI  - The non-innocent phenalenyl unit: an electronic nest to modulate the catalytic
      activity in hydroamination reaction.
AB  - The phenalenyl unit has played intriguing role in different fields of research
      spanning from chemistry, material chemistry to device physics acting as key
      electronic reservoir which has not only led to the best organic single component
      conductor but also created the spin memory device of next generation. Now we show
      the non-innocent behaviour of phenalenyl unit in modulating the catalytic
      behaviour in a homogeneous organic transformation. The present study establishes
      that the cationic state of phenalenyl unit can act as an organic Lewis acceptor
      unit to influence the catalytic outcome of intermolecular hydroamination reaction
      of carbodiimides. For the present study, we utilized organoaluminum complexes of
      phenalenyl ligands in which the phenalenyl unit maintains the closed shell
      electronic state. The DFT calculation reveals that the energy of LUMO of the
      catalyst is mainly controlled by phenalenyl ligands which in turn determines the
      outcome of the catalysis. 

PMID- 24084654
TI  - Designing large-plane conjugated copolymers for the high-yield sorting of
      semiconducting single-walled carbon nanotubes.
AB  - Semiconducting single-walled carbon nanotubes could be selectively dispersed with
      a novel fluorene-peri-xanthenoxanthene conjugated copolymer. The fabricated thin
      film field effect transistors show excellent and uniform performances with on/off
      ratios of >10(7) and mobilities of 4-6.1 cm(2) V(-1) s(-1). 

PMID- 24084655
TI  - Autoimmune liver disease, autoimmunity and liver transplantation.
AB  - Primary biliary cirrhosis (PBC), primary sclerosing cholangitis (PSC) and
      autoimmune hepatitis (AIH) represent the three major autoimmune liver diseases
      (AILD). PBC, PSC, and AIH are all complex disorders in that they result from the
      effects of multiple genes in combination with as yet unidentified environmental
      factors. Recent genome-wide association studies have identified numerous risk
      loci for PBC and PSC that host genes involved in innate or acquired immune
      responses. These loci may provide a clue as to the immune-based pathogenesis of
      AILD. Moreover, many significant risk loci for PBC and PSC are also risk loci for
      other autoimmune disorders, such type I diabetes, multiple sclerosis and
      rheumatoid arthritis, suggesting a shared genetic basis and possibly similar
      molecular pathways for diverse autoimmune conditions. There is no curative
      treatment for all three disorders, and a significant number of patients
      eventually progress to end-stage liver disease requiring liver transplantation
      (LT). LT in this context has a favourable overall outcome with current patient
      and graft survival exceeding 80% at 5years. Indications are as for other chronic
      liver disease although recent data suggest that while lethargy improves after
      transplantation, the effect is modest and variable so lethargy alone is not an
      indication. In contrast, pruritus rapidly responds. Cholangiocarcinoma, except
      under rigorous selection criteria, excludes LT because of the high risk of
      recurrence. All three conditions may recur after transplantation and are
      associated with a greater risk of both acute cellular and chronic ductopenic
      rejection. It is possible that a crosstalk between alloimmune and autoimmune
      response perpetuate each other. An immunological response toward self- or allo
      antigens is well recognised after LT in patients transplanted for non-autoimmune
      indications and sometimes termed "de novo autoimmune hepatitis". Whether this is
      part of the spectrum of rejection or an autoimmune process is not clear. In this
      manuscript, we review novel findings about disease processes and mechanisms that
      lead to autoimmunity in the liver and their possible involvement in the immune
      response vs. the graft after LT. 

PMID- 24084656
TI  - Elastic bending modulus of single-layer molybdenum disulfide (MoS2): finite
      thickness effect.
AB  - We derive, from an empirical interaction potential, an analytic formula for the
      elastic bending modulus of single-layer MoS2 (SLMoS2). By using this approach, we
      do not need to define or estimate a thickness value for SLMoS2, which is
      important due to the substantial controversy in defining this value for two
      dimensional or ultrathin nanostructures such as graphene and nanotubes. The
      obtained elastic bending modulus of 9.61 eV in SLMoS2 is significantly higher
      than the bending modulus of 1.4 eV in graphene, and is found to be within the
      range of values that are obtained using thin shell theory with experimentally
      obtained values for the elastic constants of SLMoS2. This increase in bending
      modulus as compared to monolayer graphene is attributed, through our analytic
      expression, to the finite thickness of SLMoS2. Specifically, while each monolayer
      of S atoms contributes 1.75 eV to the bending modulus, which is similar to the
      1.4 eV bending modulus of monolayer graphene, the additional pairwise and angular
      interactions between out of plane Mo and S atoms contribute 5.84 eV to the
      bending modulus of SLMoS2.

PMID- 24084657
TI  - Waiter, there is a fly in my soup!

PMID- 24084658
TI  - Perspectives on the PQRI Extractables and Leachables "Safety Thresholds and Best
      Practices" Recommendations for Inhalation Drug Products.
AB  - In 2006, the Product Quality Research Institute's (PQRI) Leachables and
      Extractables Working Group released a comprehensive and detailed recommendation
      document related to leachables and extractables for inhalation drug products. The
      document includes best pharmaceutical development practice recommendations
      regarding container closure/delivery system component composition and selection,
      controlled extraction studies, drug product leachables studies, and routine
      extractables testing for component release. Also included in the document are two
      safety-based thresholds for leachables in inhalation drug products, the
      qualification threshold (QT) and the safety concern threshold (SCT), the first
      such safety-based thresholds for leachables in any drug product type. A process
      was described for converting the SCT into an analytically useful threshold for
      leachables/extractables characterization, the analytical evaluation threshold
      (AET), with consideration of individual drug product dosing parameters and
      container closure system component characteristics. This commentary presents the
      history and evolution of this recommendation document starting from the
      propellant changeover (chlorofluorocarbons to hydrofluorocarbons) in metered dose
      inhaler drug products, which helped prompt interest in inhalation drug product
      leachables, through the work process of the PQRI group. The overall positive
      acceptance of the PQRI recommendations is discussed, along with a brief summary
      of regulatory initiatives influenced by the recommendations. Also presented and
      discussed are certain key issues and questions that have arisen since the
      recommendation document was released. The extension and application of best
      practice recommendations to other high risk drug product types (e.g., large and
      small volume parenterals, ophthalmics), led by the PQRI Parenteral and Ophthalmic
      Drug Product Working Group, is introduced and considered. LAY ABSTRACT: The
      recommendation document released by the Product Quality Research Institute's
      (PQRI) Leachables and Extractables Working Group in 2006 includes the first
      safety-based thresholds for leachables in any drug product type, along with
      comprehensive best practice recommendations for inhalation drug product
      pharmaceutical development related to extractables and leachables. The best
      practice recommendations encompass a number of important functional areas,
      including container closure/delivery system component composition and selection,
      controlled extraction studies, drug product leachables studies, and routine
      extractables testing for component release. This commentary presents the history
      and evolution of this recommendation document starting from the propellant
      changeover (chlorofluorocarbons to hydrofluorocarbons) in metered dose inhaler
      drug products, which helped prompt interest in inhalation drug product
      leachables, through the work process of the PQRI group. The overall positive
      acceptance of the PQRI recommendations is discussed, along with a brief summary
      of regulatory initiatives influenced by the recommendations. Also presented and
      discussed are certain key issues and questions that have arisen since the
      recommendation document was released. The extension and application of best
      practice recommendations to other drug product types (e.g., large- and small
      volume parenterals, ophthalmics), led by the PQRI Parenteral and Ophthalmic Drug
      Product Working Group, is introduced and considered.

PMID- 24084659
TI  - The Product Quality Research Institute (PQRI) Leachables and Extractables Working
      Group Initiatives for Parenteral and Ophthalmic Drug Product (PODP).
AB  - The Product Quality Research Institute (PQRI) is a non-profit consortium of
      organizations working together to generate and share timely, relevant, and
      impactful information that advances drug product quality and development. The
      collaborative activities of PQRI participants have, in the case of orally inhaled
      and nasal drug products (OINDPs), resulted in comprehensive and widely-accepted
      recommendations for leachables assessments to help ensure patient safety with
      respect to this class of packaged drug products. These recommendations, which
      include scientifically justified safety thresholds for leachables, represent a
      significant milestone towards establishing standardized approaches for safety
      qualification of leachables in OINDP. To build on the success of the OINDP
      effort, PQRI's Parenteral and Ophthalmic Drug Products (PODP) Leachables and
      Extractables Working Group was formed to extrapolate the OINDP threshold concepts
      and best practice recommendations to other dosage forms with high concern for
      interaction with packaging/delivery systems. This article considers the general
      aspects of leachables and their safety assessment, introduces the PODP Work Plan
      and initial study Protocol, discusses the laboratory studies being conducted by
      the PODP Chemistry Team, outlines the strategy being developed by the PODP
      Toxicology Team for the safety qualification of PODP leachables, and considers
      the issues associated with application of the safety thresholds, particularly
      with respect to large-volume parenterals. Lastly, the unique leachables issues
      associated with biologics are described. LAY ABSTRACT: The Product Quality
      Research Institute (PQRI) is a non-profit consortium involving industry
      organizations, academia, and regulatory agencies that together provide
      recommendations in support of regulatory guidance to advance drug product
      quality. The collaborative activities of the PQRI Orally Inhaled and Nasal Drug
      Products Leachables and Extractables Working Group resulted in a systematic and
      science-based approach to identify and qualify leachables, including the concept
      of safety thresholds. Concepts from this widely accepted approach, formally
      publicized in 2006, are being extrapolated to parenteral and ophthalmic drug
      products. This article provides an overview of extractables and leachables in
      drug products and biologics and discusses the PQRI Work Plan and Protocols
      developed by the PQRI Parenteral and Ophthalmic Drug Products Leachables and
      Extractables Working Group.

PMID- 24084660
TI  - Extractables characterization for five materials of construction representative
      of packaging systems used for parenteral and ophthalmic drug products.
AB  - Polymeric and elastomeric materials are commonly encountered in medical devices
      and packaging systems used to manufacture, store, deliver, and/or administer drug
      products. Characterizing extractables from such materials is a necessary step in
      establishing their suitability for use in these applications. In this study, five
      individual materials representative of polymers and elastomers commonly used in
      packaging systems and devices were extracted under conditions and with solvents
      that are relevant to parenteral and ophthalmic drug products (PODPs). Extraction
      methods included elevated temperature sealed vessel extraction, sonication,
      refluxing, and Soxhlet extraction. Extraction solvents included a low-pH (pH =
      2.5) salt mixture, a high-pH (pH = 9.5) phosphate buffer, a 1/1 isopropanol/water
      mixture, isopropanol, and hexane. The resulting extracts were chemically
      characterized via spectroscopic and chromatographic means to establish the
      metal/trace element and organic extractables profiles. Additionally, the test
      articles themselves were tested for volatile organic substances. The results of
      this testing established the extractables profiles of the test articles, which
      are reported herein. Trends in the extractables, and their estimated
      concentrations, as a function of the extraction and testing methodologies are
      considered in the context of the use of the test article in medical applications
      and with respect to establishing best demonstrated practices for extractables
      profiling of materials used in PODP-related packaging systems and devices. LAY
      ABSTRACT: Plastic and rubber materials are commonly encountered in medical
      devices and packaging/delivery systems for drug products. Characterizing the
      extractables from these materials is an important part of determining that they
      are suitable for use. In this study, five materials representative of plastics
      and rubbers used in packaging and medical devices were extracted by several
      means, and the extracts were analytically characterized to establish each
      material's profile of extracted organic compounds and trace element/metals. This
      information was utilized to make generalizations about the appropriateness of the
      test methods and the appropriate use of the test materials.

PMID- 24084661
TI  - Evaluation of a rapid microbiological method with a mixed culture biofilm model.
AB  - During the past decade, rapid microbiological methods (RMMs) have continued to
      make inroads into the pharmaceutical and medical device industries. This has led
      to the development of guidelines for the validation of alternative
      microbiological methods for both quantitative and qualitative applications. Many
      studies regarding RMMs have focused on testing performed with planktonic
      microorganisms. In some applications there is the possibility that microorganisms
      may also be present as biofilms. When evaluating an RMM, consideration should be
      given to the potential for biofilm formation within the context of the
      application and whether microorganisms derived from biofilm would influence the
      response of the method. This study reflects the evaluation of an RMM with both
      planktonic microorganisms and microorganisms derived from a mixed culture
      biofilm. LAY ABSTRACT: Many new rapid microbiological methods (RMMs) have been
      developed that have the potential to replace conventional microbiological methods
      in a wide range of applications including sterility testing, microbial
      enumeration, environmental monitoring, microbial identification, and other areas.
      Qualification of these new methods is frequently based on testing performed with
      planktonic (non-aggregated) microorganisms. However, microorganisms can aggregate
      together to form biofilms in both natural and manufacturing environments.
      Purified water systems in particular may be susceptible to the development of
      biofilms. Because the properties of microorganisms in a biofilm may differ from
      those in a planktonic state, qualification of an RMM with microorganisms derived
      from a relevant biofilm model may be appropriate depending on the application and
      the potential for biofilm formation. This study describes the evaluation of one
      such RMM, the Chemunex ScanRDI(r), with both planktonic microorganisms and
      microorganisms derived from a mixed culture biofilm model.

PMID- 24084662
TI  - Setting Specifications of Correlated Quality Attributes through Multivariate
      Statistical Modelling.
AB  - Specifications of drug products are quality standards that provide assurance that
      the drug is fit for its intended use. Establishment of specifications limits
      relies on data collected during the life cycle of a product, including those from
      preclinical and clinical trials, stability studies, and process validation, and
      often requires application of appropriate statistical methods. While quality
      attributes may be correlated, specifications are often determined without taking
      into account possible interdependence. Such practice may potentially result in
      specifications that are narrower than acceptable ranges of product performance.
      Through a case study, this paper discusses how this issue can be coped with
      effectively by using multivariate statistical modelling. LAY ABSTRACT:
      Specifications of drug products are quality standards that provide assurance that
      the drug is fit for its intended use. Specifications are conventionally set up
      separately for each of the quality attributes of interest, without accounting for
      interdependence among the quality attributes. Such practice may potentially
      result in specifications that are narrower than acceptable ranges of product
      performance. Through a case study, this paper discusses how this issue can be
      coped with effectively by using statistical modelling.

PMID- 24084663
TI  - Application of the Finite Elemental Analysis to Modeling Temperature Change of
      the Vaccine in an Insulated Packaging Container during Transport.
AB  - This study demonstrated an attempt to predict temperatures of a perishable
      product such as vaccine inside an insulated packaging container during transport
      through finite element analysis (FEA) modeling. In order to use the standard FEA
      software for simulation, an equivalent heat conduction coefficient is proposed
      and calculated to describe the heat transfer of the air trapped inside the
      insulated packaging container. The three-dimensional, insulated packaging
      container is regarded as a combination of six panels, and the heat flow at each
      side panel is a one-dimension diffusion process. The transit-thermal analysis was
      applied to simulate the heat transition process from ambient environment to
      inside the container. Field measurements were carried out to collect the
      temperature during transport, and the collected data were compared to the FEA
      simulation results. LAY ABSTRACT: Insulated packaging containers are used to
      transport temperature-sensitive products such as vaccine and other pharmaceutical
      products. The container is usually made of an extruded polystyrene foam filled
      with gel packs. World Health Organization guidelines recommend that all vaccines
      except oral polio vaccine be distributed in an environment where the temperature
      ranges between +2 to +8  degrees C. The primary areas of concern in designing the
      packaging for vaccine are how much of the foam thickness and gel packs should be
      used in order to keep the temperature in a desired range, and how to prevent the
      vaccine from exposure to freezing temperatures. This study uses numerical
      simulation to predict temperature change within an insulated packaging container
      in vaccine cold chain. It is our hope that this simulation will provide the
      vaccine industries with an alternative engineering tool to validate vaccine
      packaging and project thermal equilibrium within the insulated packaging
      container.

PMID- 24084664
TI  - The application of quality risk management to the bacterial endotoxins test: use
      of hazard analysis and critical control points.
AB  - Risk analysis is widely used in the pharmaceutical industry to manage production
      processes, validation activities, training, and other activities. Several methods
      of risk analysis are available (for example, failure mode and effects analysis,
      fault tree analysis), and one or more should be chosen and adapted to the
      specific field where they will be applied. Among the methods available, hazard
      analysis and critical control points (HACCP) is a methodology that has been
      applied since the 1960s, and whose areas of application have expanded over time
      from food to the pharmaceutical industry. It can be easily and successfully
      applied to several processes because its main feature is the identification,
      assessment, and control of hazards. It can be also integrated with other tools,
      such as fishbone diagram and flowcharting. The aim of this article is to show how
      HACCP can be used to manage an analytical process, propose how to conduct the
      necessary steps, and provide data templates necessary to document and useful to
      follow current good manufacturing practices. LAY ABSTRACT: In the quality control
      process, risk analysis is a useful tool for enhancing the uniformity of technical
      choices and their documented rationale. Accordingly, it allows for more effective
      and economical laboratory management, is capable of increasing the reliability of
      analytical results, and enables auditors and authorities to better understand
      choices that have been made. The aim of this article is to show how hazard
      analysis and critical control points can be used to manage bacterial endotoxins
      testing and other analytical processes in a formal, clear, and detailed manner.

PMID- 24084665
TI  - State-to-state resolved differential cross sections for rotationally inelastic
      scattering of ND3 with He.
AB  - State-to-state differential cross sections are reported for rotationally
      inelastic scattering of fully state-selected ND3 (j(k)(+/-) = 1(1)(-)) with He.
      Experimental measurements are compared with full close-coupling quantum
      mechanical scattering calculations that used an ab initio potential energy
      surface. Results are presented for final states up to j'(k')(+/-) = 7(7)(-) at a
      mean collision energy of 430 cm(-1). For selected final quantum states, the
      effect of collision energy on the differential cross sections is also explored in
      the range 230-720 cm(-1). For the experimental studies, a hexapole electrostatic
      lens was used for the j(k)(+/-) state-selection of ND3 molecules in their
      electronic and vibrational ground states in a molecular beam. This state-selected
      molecular beam was then crossed with a beam of He atoms. The velocities of
      inelastically scattered ND3 molecules in single j'(k')(+/-) states were obtained
      by velocity map imaging, and converted to differential cross sections in the
      centre-of-mass frame by density-to-flux transformation. The close-coupling
      calculations reproduce well the measured angular distributions. For small changes
      in the rotational angular momentum quantum number (j), the ND3 is predominantly
      forward scattered, but the scattering shifts to the sideways and backward
      directions as Deltaj increases. For scattering into a given j'(k')(+/-) state,
      cross-sections for collisions that conserve the +/- symmetry associated with the
      ND3 inversion vibration are larger and generally more forward scattered than the
      corresponding symmetry-changing processes.

PMID- 24084666
TI  - [Revolution in interventional cardiology: the fully bioresorbable vascular
      scaffold. Presentation].

PMID- 24084667
TI  - [Structure and function of the fully bioresorbable vascular scaffold].

PMID- 24084668
TI  - [Clinical trials evaluating the Absorb bioresorbable vascular scaffold].

PMID- 24084669
TI  - [Who is the ideal patient for treatment with the AbsorbTM bioresorbable vascular
      scaffold?].

PMID- 24084670
TI  - Estimated drinking water fluoride exposure and risk of hip fracture: a cohort
      study.
AB  - The cariostatic benefit from water fluoridation is indisputable, but the
      knowledge of possible adverse effects on bone and fracture risk due to fluoride
      exposure is ambiguous. The association between long-term (chronic) drinking water
      fluoride exposure and hip fracture (ICD-7-9: '820' and ICD-10: 'S72.0-S72.2') was
      assessed in Sweden using nationwide registers. All individuals born in Sweden
      between January 1, 1900 and December 31, 1919, alive and living in their
      municipality of birth at the time of start of follow-up, were eligible for this
      study. Information on the study population (n = 473,277) was linked among the
      Swedish National In-Patient Register (IPR), the Swedish Cause of Death Register,
      and the Register of Population and Population Changes. Estimated individual
      drinking water fluoride exposure was stratified into 4 categories: very low, <
      0.3 mg/L; low, 0.3 to 0.69 mg/L; medium, 0.7 to 1.49 mg/L; and high, >= 1.5 mg/L.
      Overall, we found no association between chronic fluoride exposure and the
      occurrence of hip fracture. The risk estimates did not change in analyses
      restricted to only low-trauma osteoporotic hip fractures. Chronic fluoride
      exposure from drinking water does not seem to have any important effects on the
      risk of hip fracture, in the investigated exposure range. 

PMID- 24084672
TI  - Participatory research revealing the work and occupational health hazards of
      cooperative recyclers in Brazil.
AB  - Although informal waste collectors are sometimes organized in cooperatives, their
      working conditions remain extremely precarious and unsafe. The paper discusses
      the findings of action oriented, participatory qualitative research with several
      recycling groups in the metropolitan region of Sao Paulo, Brazil. During
      workshops with the recyclers mapping, acting, and drawing methods helped reveal
      health hazards from collection, separation and transportation of recyclable
      materials. Major health problems relate to chemical and biological hazards,
      musculoskeletal damage, mechanical trauma and poor emotional wellbeing. The
      recent federal legislation on solid waste management opens new avenues for the
      inclusion of recycling cooperatives in selective waste collection. Nevertheless,
      we express the need to consider the distinctive characteristics and
      vulnerabilities of recycling groups, when developing safer work environments in
      these social businesses. We also suggest that the workspace be ergonomically
      organized and that public awareness campaigns about selective waste collection
      are conducted regularly to increase the quality of source separation. The
      introduction of electric hand pushed carts can further reduce health strains.
      This research has produced a better understanding of the work of the recyclers
      and related health risks. The interactive qualitative research methodology has
      allowed for the co-creation and mobilization of specific knowledge on health and
      safety in recycling cooperatives. 

PMID- 24084673
TI  - The effectiveness of drinking and driving policies for different alcohol-related
      fatalities: a quantile regression analysis.
AB  - To understand the impact of drinking and driving laws on drinking and driving
      fatality rates, this study explored the different effects these laws have on
      areas with varying severity rates for drinking and driving. Unlike previous
      studies, this study employed quantile regression analysis. Empirical results
      showed that policies based on local conditions must be used to effectively reduce
      drinking and driving fatality rates; that is, different measures should be
      adopted to target the specific conditions in various regions. For areas with low
      fatality rates (low quantiles), people's habits and attitudes toward alcohol
      should be emphasized instead of transportation safety laws because "preemptive
      regulations" are more effective. For areas with high fatality rates (or high
      quantiles), "ex-post regulations" are more effective, and impact these areas
      approximately 0.01% to 0.05% more than they do areas with low fatality rates. 

PMID- 24084671
TI  - Alcohol and violence in the emergency room: a review and perspectives from
      psychological and social sciences.
AB  - Our objective is to present a focused review of the scientific literature on the
      effect of alcohol consumption on violence related-injuries assessed in the
      emergency room (ER) and to show how psychological and behavioral sciences could
      lead to a better understanding of the factors contributing to alcohol-related
      injuries in the ER. We retrieved published literature through a detailed search
      in Academic Search Premier, MEDLINE with Full Text PsycARTICLES, Psychology and
      Behavioral Sciences Collection, PsycINFO, PUBMed and SocINDEX with Full Text for
      articles related to emergency rooms, medical problems and sociocognitive models
      addressing alcohol intoxication articles. The first search was conducted in June
      2011 and updated until August 2013. Literature shows that compared to uninjured
      patients; injured ones have a higher probability of: (i) having an elevated blood
      alcohol concentration upon arrival at the ER; (ii) reporting having drunk alcohol
      during the six hours preceding the event; and (iii) suffering from drinking
      related consequences that adversely affect their social life. The main
      neurocognitive and sociocognitive models on alcohol and aggression are also
      discussed in order to understand the aetiology of violence-related injuries in
      emergency rooms. Suggestions are made for future research and prevention. 

PMID- 24084674
TI  - Use or non-use of gerontechnology--a qualitative study.
AB  - This study employed a qualitative approach to explore the attitudes and
      experiences of older people towards using gerontechnology, and to determine the
      underlying reasons that might account for their use and non-use of
      gerontechnology. Four focus group discussions and 26 individual interviews were
      undertaken. Qualitative data were analyzed using NVivo software and were
      categorized using coding and grounded theory techniques. The result indicated
      that old people in Hong Kong had an overall positive attitude toward technology.
      Positive attitudes were most frequently related to enhanced convenience and
      advanced features. Negative attitudes were most frequently associated with health
      risks and social problems arising from using technology (e.g., social isolation
      and addiction). Usage of technology is driven by outcome expectations and social
      influences, and supported by facilitators, whereas non-use of gerontechnology
      relates to the personal (e.g., health and functional capacities), technological
      (e.g., cost and complexity), and environmental barriers experienced. Use of
      gerontechnology is a synthesis of person, technology, and environment. To
      encourage non-users to adopt technology, there is a need to remove barriers at
      personal, technological, and environmental levels. 

PMID- 24084676
TI  - The complex epidemiological scenario of West Nile virus in Italy.
AB  - Entomological, veterinary, and human surveillance systems for West Nile virus
      (WNV) infection have been implemented in Italy since the first detection of the
      virus in 1998. These surveillance activities documented a progressive increase of
      WNV activity and spread in different regions and the emergence of new WNV
      lineages and strains. Italy is a paradigmatic example of the complex epidemiology
      of WNV in Europe, where sporadic cases of WNV infection, clusters, and small
      outbreaks have been reported in several regions. In addition, different strains
      of both WNV lineage 1 and lineage 2 have been identified, even co-circulating in
      the same area. 

PMID- 24084677
TI  - Was mandatory quarantine necessary in China for controlling the 2009 H1N1
      pandemic?
AB  - The Chinese government enforced mandatory quarantine for 60 days (from 10 May to
      8 July 2009) as a preventative strategy to control the spread of the 2009 H1N1
      pandemic. Such a prevention strategy was stricter than other non-pharmaceutical
      interventions that were carried out in many other countries. We evaluated the
      effectiveness of the mandatory quarantine and provide suggestions for
      interventions against possible future influenza pandemics. We selected one city,
      Beijing, as the analysis target. We reviewed the epidemiologic dynamics of the
      2009 H1N1 pandemic and the implementation of quarantine measures in Beijing. The
      infectious population was simulated under two scenarios (quarantined and not
      quarantined) using a deterministic Susceptible-Exposed-Infectious-Recovered
      (SEIR) model. The basic reproduction number R0 was adjusted to match the epidemic
      wave in Beijing. We found that mandatory quarantine served to postpone the spread
      of the 2009 H1N1 pandemic in Beijing by one and a half months. If mandatory
      quarantine was not enforced in Beijing, the infectious population could have
      reached 1,553 by 21 October, i.e., 5.6 times higher than the observed number.
      When the cost of quarantine is taken into account, mandatory quarantine was not
      an economically effective intervention approach against the 2009 H1N1 pandemic.
      We suggest adopting mitigation methods for an influenza pandemic with low
      mortality and morbidity. 

PMID- 24084678
TI  - Evidence for long-term impact of Pasos Adelante: using a community-wide survey to
      evaluate chronic disease risk modification in prior program participants.
AB  - Effective community-level chronic disease prevention is critical to population
      health within developed and developing nations. Pasos Adelante is a preventive
      intervention that aims to reduce chronic disease risk with evidence of
      effectiveness in US-Mexico residing, Mexican origin, participants. This
      intervention and related ones also implemented with community health workers have
      been shown to improve clinical, behavioral and quality of life indicators; though
      most evidence is from shorter-term evaluations and/or lack comparison groups. The
      current study examines the impact of this program using secondary data collected
      in the community 3-6 years after all participants completed the program. A
      proportional household survey (N = 708) was used that included 48 respondents who
      indicated they had participated in Pasos. Using propensity score matching to
      account for differences in program participants versus other community residents
      (the program targeted those with diabetes and associated risk factors), 148
      natural controls were identified for 37 matched Pasos participants. Testing a
      range of behavioral and clinical indicators of chronic disease risk, logistic
      regression models accounting for selection bias showed two significant findings;
      Pasos participants were more physically active and drank less whole milk. These
      findings add to the evidence of the effectiveness of Pasos Adalente and related
      interventions in reducing chronic disease risk in Mexican-origin populations, and
      illustrate the use of innovative techniques for using secondary, community-level
      data to complement prior evaluation research. 

PMID- 24084679
TI  - West Nile virus transmission in sentinel chickens and potential mosquito vectors,
      Senegal River Delta, 2008-2009.
AB  - West Nile virus (WNV) is an arthropod-borne Flavivirus usually transmitted to
      wild birds by Culex mosquitoes. Humans and horses are susceptible to WNV but are
      dead-end hosts. WNV is endemic in Senegal, particularly in the Senegal River
      Delta. To assess transmission patterns and potential vectors, entomological and
      sentinel serological was done in Ross Bethio along the River Senegal. Three
      sentinel henhouses (also used as chicken-baited traps) were set at 100 m, 800 m,
      and 1,300 m from the river, the latter close to a horse-baited trap. Blood
      samples were taken from sentinel chickens at 2-week intervals. Seroconversions
      were observed in sentinel chickens in November and December. Overall, the
      serological incidence rate was 4.6% with 95% confidence interval (0.9; 8.4) in
      the sentinel chickens monitored for this study. Based on abundance pattern, Culex
      neavei was the most likely mosquito vector involved in WNV transmission to
      sentinel chickens, and a potential bridge vector between birds and mammals. 

PMID- 24084680
TI  - Management of atrial fibrillation in seven European countries after the
      publication of the 2010 ESC Guidelines on atrial fibrillation: primary results of
      the PREvention oF thromboemolic events--European Registry in Atrial Fibrillation
      (PREFER in AF).
AB  - AIMS: We sought to describe the management of patients with atrial fibrillation
      (AF) in Europe after the release of the 2010 AF Guidelines of the European
      Society of Cardiology. METHODS AND RESULTS: The PREFER in AF registry enrolled
      consecutive patients with AF from January 2012 to January 2013 in 461 centres in
      seven European countries. Seven thousand two hundred and forty-three evaluable
      patients were enrolled, aged 71.5 +/- 11 years, 60.1% male, CHA2DS2VASc score 3.4
      +/- 1.8 (mean +/- standard deviation). Thirty per cent patients had paroxysmal,
      24.0% had persistent, 7.2% had long-standing persistent, and 38.8% had permanent
      AF. Oral anticoagulation was used in the majority of patients: 4799 patients
      (66.3%) received a vitamin K antagonist (VKA) as mono-therapy, 720 patients a
      combination of VKA and antiplatelet agents (9.9%), 442 patients (6.1%) a new oral
      anticoagulant drugs (NOAC). Antiplatelet agents alone were given to 808 patients
      (11.2%), no antithrombotic therapy to 474 patients (6.5%). Of 7034 evaluable
      patients, 5530 (78.6%) patients were adequately rate controlled (mean heart rate
      60-100 bpm). Half of the patients (50.7%) received rhythm control therapy by
      electrical cardioversion (18.1%), pharmacological cardioversion (19.5%),
      antiarrhythmic drugs (amiodarone 24.1%, flecainide or propafenone 13.5%, sotalol
      5.5%, dronedarone 4.0%), and catheter ablation (5.0%). CONCLUSION: The management
      of AF patients in 2012 has adapted to recent evidence and guideline
      recommendations. Oral anticoagulant therapy with VKA (majority) or NOACs is given
      to over 80% of eligible patients, including those at risk for bleeding. Rate is
      often adequately controlled, and rhythm control therapy is widely used.

PMID- 24084681
TI  - Studies on pyranonigrins-isolation of pyranonigrin E and biosynthetic studies on
      pyranonigrin A.

PMID- 24084682
TI  - In vitro antitrypanosomal activity of the cyclodepsipeptides, cardinalisamides A
      C, from the insect pathogenic fungus Cordyceps cardinalis NBRC 103832.
AB  - During the search for new antitrypanosomal drug leads, three new antitrypanosomal
      compounds, cardinalisamides A-C (1-3), were isolated from cultures of the insect
      pathogenic fungus Cordyceps cardinalis NBRC 103832. Their structures were
      elucidated using MS analyses and extensive 2D-heteronuclear NMR. The absolute
      configurations of 1-3 were addressed by chemical degradation and Marfey's
      analysis. 1-3 showed in vitro antitrypanosomal activity against Trypanosoma
      brucei brucei with IC50 values of 8.56, 8.65 and 8.63 MUg ml(-1), respectively. 

PMID- 24084683
TI  - Study on retroaldol degradation products of antibiotic oligomycin A.
AB  - Studies of reactivity of antibiotic oligomycin A in various alkaline conditions
      showed that the compound easily undergoes retroaldol degradation in beta-hydroxy
      ketone fragments positioned in the C7-C13 moiety of the antibiotic molecule.
      Depending on reaction conditions, the retroaldol fragmentation of the 8,9 or
      12,13 bonds or formation of a product through double retroaldol degradation, when
      the fragment C9-C12 was detached, took place followed by further transformations
      of the intermediate aldehydes formed. The structures of the obtained non-cyclic
      derivatives of oligomycin A were supported by NMR and MS methods. NMR parameters
      demonstrate the striking similarity of the geometry (conformation) of the
      fragment C20-C34 in the non-cyclic products of retroaldol degradation and the
      starting antibiotic 1. The compounds obtained had lower cytototoxic properties
      than oligomycin A for human leukemia cells K-562 and colon cancer cells HCT-116
      and lower activity against growth inhibition of model object Streptomyces
      fradiae. It cannot be excluded that the products of retroaldol degradation
      participate in the biological effects of antibiotic oligomycin A. 

PMID- 24084684
TI  - Tensile testing of ultra-thin films on water surface.
AB  - The surface of water provides an excellent environment for gliding movement, in
      both nature and modern technology, from surface living animals such as the water
      strider, to Langmuir-Blodgett films. The high surface tension of water keeps the
      contacting objects afloat, and its low viscosity enables almost frictionless
      sliding on the surface. Here we utilize the water surface as a nearly ideal
      underlying support for free-standing ultra-thin films and develop a novel tensile
      testing method for the precise measurement of mechanical properties of the films.
      In this method, namely, the pseudo free-standing tensile test, all specimen
      preparation and testing procedures are performed on the water surface, resulting
      in easy handling and almost frictionless sliding without specimen damage or
      substrate effects. We further utilize van der Waals adhesion for the damage-free
      gripping of an ultra-thin film specimen. Our approach can potentially be used to
      explore the mechanical properties of emerging two-dimensional materials.

PMID- 24084685
TI  - Metabolic labeling of leucine rich repeat kinases 1 and 2 with radioactive
      phosphate.
AB  - Leucine rich repeat kinases 1 and 2 (LRRK1 and LRRK2) are paralogs which share a
      similar domain organization, including a serine-threonine kinase domain, a Ras of
      complex proteins domain (ROC), a C-terminal of ROC domain (COR), and leucine-rich
      and ankyrin-like repeats at the N-terminus. The precise cellular roles of LRRK1
      and LRRK2 have yet to be elucidated, however LRRK1 has been implicated in
      tyrosine kinase receptor signaling, while LRRK2 is implicated in the pathogenesis
      of Parkinson's disease. In this report, we present a protocol to label the LRRK1
      and LRRK2 proteins in cells with (32)P orthophosphate, thereby providing a means
      to measure the overall phosphorylation levels of these 2 proteins in cells. In
      brief, affinity tagged LRRK proteins are expressed in HEK293T cells which are
      exposed to medium containing (32)P-orthophosphate. The (32)P-orthophosphate is
      assimilated by the cells after only a few hours of incubation and all molecules
      in the cell containing phosphates are thereby radioactively labeled. Via the
      affinity tag (3xflag) the LRRK proteins are isolated from other cellular
      components by immunoprecipitation. Immunoprecipitates are then separated via SDS
      PAGE, blotted to PVDF membranes and analysis of the incorporated phosphates is
      performed by autoradiography ((32)P signal) and western detection (protein
      signal) of the proteins on the blots. The protocol can readily be adapted to
      monitor phosphorylation of any other protein that can be expressed in cells and
      isolated by immunoprecipitation.

PMID- 24084687
TI  - Isolation of myeloid dendritic cells and epithelial cells from human thymus.
AB  - In this protocol we provide a method to isolate dendritic cells (DC) and
      epithelial cells (TEC) from the human thymus. DC and TEC are the major antigen
      presenting cell (APC) types found in a normal thymus and it is well established
      that they play distinct roles during thymic selection. These cells are localized
      in distinct microenvironments in the thymus and each APC type makes up only a
      minor population of cells. To further understand the biology of these cell types,
      characterization of these cell populations is highly desirable but due to their
      low frequency, isolation of any of these cell types requires an efficient and
      reproducible procedure. This protocol details a method to obtain cells suitable
      for characterization of diverse cellular properties. Thymic tissue is
      mechanically disrupted and after different steps of enzymatic digestion, the
      resulting cell suspension is enriched using a Percoll density centrifugation
      step. For isolation of myeloid DC (CD11c(+)), cells from the low-density fraction
      (LDF) are immunoselected by magnetic cell sorting. Enrichment of TEC populations
      (mTEC, cTEC) is achieved by depletion of hematopoietic (CD45(hi)) cells from the
      low-density Percoll cell fraction allowing their subsequent isolation via
      fluorescence activated cell sorting (FACS) using specific cell markers. The
      isolated cells can be used for different downstream applications. 

PMID- 24084688
TI  - Conformational control of benzophenone-sensitized charge transfer in
      dinucleotides.
AB  - Charge transfer in DNA cannot be understood without addressing the complex
      conformational flexibility, which occurs on a wide range of timescales. In order
      to reduce this complexity four dinucleotide models 1X consisting of benzophenone
      linked by a phosphodiester to one of the natural nucleosides X = A, G, T, C were
      studied in water and methanol. The theoretical work focuses on the dynamics and
      electronic structure of 1G. Predominant conformations in the two solvents were
      obtained by molecular dynamics simulations. 1G in MeOH adopts mainly an open
      geometry with a distance of 12-16 A between the two aromatic parts. In H2O the
      two parts of 1G form primarily a stacked conformation yielding a distance of 5-6
      A. The low-lying excited states were investigated by electronic structure theory
      in a QM/MM environment for representative snapshots of the trajectories. Photo
      induced intramolecular charge transfer in the S1 state occurs exclusively in the
      stacked conformation. Ultrafast transient absorption spectroscopy with 1X reveals
      fast charge transfer from S1 in both solvents with varying yields. Significant
      charge transfer from the T1 state is only found for the nucleobases with the
      lowest oxidation potential: in H2O, charge transfer occurs with 3.2 * 10(9) s(-1)
      for 1A and 6.0 * 10(9) s(-1) for 1G. The reorganization energy remains nearly
      unchanged going from MeOH to the more polar H2O. The electronic coupling is
      rather low even for the stacked conformation with H(AB) = 3 meV and explains the
      moderate charge transfer rates. The solvent controls the conformational
      distribution and therefore gates the charge transfer due to differences in
      distance and stacking.

PMID- 24084689
TI  - Isoflurane on brain inflammation.
AB  - Brain inflammation may play an important role in the pathophysiology of early
      brain injury after subarachnoid hemorrhage (SAH). Our aim was to demonstrate
      brain inflammation development and to determine whether isoflurane, a clinically
      available volatile anesthetic agent, prevents brain inflammation after SAH. This
      study used 162 8-week-old male CD-1 mice. We induced SAH with endovascular
      perforation in mice and randomly assigned animals to sham-operated (n=21),
      SAH+vehicle-air (n=35) and SAH+2% isoflurane (n=31). In addition to the
      evaluation of brain injury (neurological scores, brain edema and Evans blue dye
      extravasation), brain inflammation was evaluated by means of expression changes
      in markers of inflammatory cells (ionized calcium binding adaptor molecule-1,
      myeloperoxidase), cytokines (tumor necrosis factor [TNF]-alpha, interleukin
      1beta), adhesion molecules (intercellular adhesion molecule [ICAM]-1, P
      selectin), inducers of inflammation (cyclooxygenase-2, phosphorylated c-Jun N
      terminal kinase [p-JNK]) and endothelial cell activation (von Willebrand factor)
      at 24h post-SAH. Sphingosine kinase inhibitor (N, N-dimethylsphingosine [DMS])
      and sphingosine-1-phosphate receptor-1/3 antagonist (VPC23019) were used to block
      isoflurane's effects (n=22, each). SAH caused early brain injury, which was
      associated with inflammation so that all evaluated markers of inflammation were
      increased. Isoflurane significantly inhibited both brain injury (P<0.001,
      respectively) and inflammation (myeloperoxidase, P=0.022; interleukin-1beta,
      P=0.002; TNF-alpha, P=0.015; P-selectin, P=0.010; ICAM-1, P=0.016; p-JNK,
      P<0.001; cyclooxygenase-2, P=0.003, respectively). This beneficial effect of
      isoflurane was abolished with DMS and VPC23019. Isoflurane may suppress post-SAH
      brain inflammation possibly via the sphingosine-related pathway. 

PMID- 24084690
TI  - Systemic delivery of microRNA-181b inhibits nuclear factor-kappaB activation,
      vascular inflammation, and atherosclerosis in apolipoprotein E-deficient mice.
AB  - RATIONALE: Activated nuclear factor (NF)-kappaB signaling in the vascular
      endothelium promotes the initiation and progression of atherosclerosis. Targeting
      endothelial NF-kappaB may provide a novel strategy to limit chronic inflammation.
      OBJECTIVE: To examine the role of microRNA-181b (miR-181b) in endothelial NF
      kappaB signaling and effects on atherosclerosis. METHODS AND RESULTS: MiR-181b
      expression was reduced in the aortic intima and plasma in apolipoprotein E
      deficient mice fed a high-fat diet. Correspondingly, circulating miR-181b in the
      plasma was markedly reduced in human subjects with coronary artery disease.
      Systemic delivery of miR-181b resulted in a 2.3-fold overexpression of miR-181b
      in the aortic intima of apolipoprotein E-deficient mice and suppressed NF-kappaB
      signaling revealed by bioluminescence imaging and reduced target gene expression
      in the aortic arch in apolipoprotein E-deficient/NF-kappaB-luciferase transgenic
      mice. MiR-181b significantly inhibited atherosclerotic lesion formation,
      proinflammatory gene expression and the influx of lesional macrophages and CD4+ T
      cells in the vessel wall. Mechanistically, miR-181b inhibited the expression of
      the target gene importin-alpha3, an effect that reduced NF-kappaB nuclear
      translocation specifically in the vascular endothelium of lesions, whereas
      surprisingly leukocyte NF-kappaB signaling was unaffected despite a 7-fold
      overexpression of miR-181b. Our findings uncover that NF-kappaB nuclear
      translocation in leukocytes does not involve importin-alpha3, but rather importin
      alpha5, which miR-181b does not target, highlighting that inhibition of NF-kappaB
      signaling in the endothelium is sufficient to mediate miR-181b's protective
      effects. CONCLUSIONS: Systemic delivery of miR-181b inhibits the activation of NF
      kappaB and atherosclerosis through cell-specific mechanisms in the vascular
      endothelium. These findings support the rationale that delivery of miR-181b may
      provide a novel therapeutic approach to treat chronic inflammatory diseases such
      as atherosclerosis.

PMID- 24084691
TI  - Inhibition of four-and-a-half LIM domain protein-2 increases survival, migratory
      capacity, and paracrine function of human early outgrowth cells through
      activation of the sphingosine kinase-1 pathway: implications for endothelial
      regeneration.
AB  - RATIONALE: Inhibition of four-and-a-half LIM domain protein-2 (FHL2) attenuates
      atherosclerotic lesion formation and increases endothelial cell migration. Early
      outgrowth cells (EOCs) contribute substantially to endothelial repair. OBJECTIVE:
      We investigated the role of FHL2 in the regulation of EOCs. METHODS AND RESULTS:
      Human EOCs were cultured from peripheral blood. FHL2 knockdown in EOCs by siRNA
      resulted in increased EOC numbers and reduced apoptosis, as indicated by
      decreased cleaved caspase-III and reduced Bax/Bcl-2 expression ratio. This was
      mediated through increased phosphorylation and membrane translocation of
      sphingosine kinase-1, increased sphingosine-1-phosphate levels, and Akt
      phosphorylation. FHL2 knockdown increased stromal cell-derived factor-1-induced
      EOC migration through upregulation of alphav/beta3, alphav/beta5, and beta2
      integrins, associated with increased cortactin expression. Reduced apoptosis,
      increased EOC migration, and cortactin upregulation by FHL2 siRNA were prevented
      by CAY10621, the sphingosine kinase-1 inhibitor, and the sphingosine-1-phosphate
      receptor-1/-3 antagonist VPC23019. These findings were confirmed using spleen
      derived EOCs from FHL2(-/-) mice. Apoptosis was decreased and migration increased
      in endothelial cells exposed to the conditioned medium of FHL2(-/-) versus wild
      type (WT) EOCs. These paracrine effects were abolished by VPC23019. Importantly,
      reendothelialization after focal carotid endothelial injury in WT mice was
      significantly increased after intravenous injection of FHL2(-/-) versus WT EOCs.
      CONCLUSIONS: Our findings suggest that FHL2 negatively regulates EOC survival,
      migration, and paracrine function. FHL2 inhibition in EOCs reduces apoptosis and
      enhances survival and migratory capacity of both EOCs and surrounding endothelial
      cells by activation of the sphingosine kinase-1/sphingosine-1-phosphate pathway,
      resulting in improvement of endothelial regeneration.

PMID- 24084693
TI  - Interference from Indian diet on the internal standard in a commercial method for
      the measurement of urinary metanephrines by high-performance liquid
      chromatography with electrochemical detection.
AB  - INTRODUCTION: Urinary metanephrines are widely used in the diagnosis of
      catecholamine secreting tumours. Over the past two years we have been using the
      commercial Recipe((r)) ClinRep((r)) Complete Kit for Metanephrines in Urine
      coupled with high-performance liquid chromatography and coulometric detection. It
      was noticed that the internal standards on the patient chromatograms were
      sporadically raised due to interference. METHODS: The interference had identical
      chromatographic and electrochemical properties to the Recipe((r)) internal
      standard (undisclosed identity). Inspection of the patient names showed it
      seemingly had a higher frequency and magnitude in patients of Indian origin. The
      source of the interference was tracked by dietary observation and intervention to
      curry leaves, a common component of Indian foods. RESULTS: The interference was
      chromatographically and electrochemically indistinguishable from the internal
      standard. The mass spectrum of the pentafluoropropionate derivative of the
      interference matched the Recipe((r)) internal standard and was identified as
      methoxyhydroxybenzylamine by library match. CONCLUSION: The component co-elutes
      exactly with internal standard and artifactually decreases the metanephrine and
      normetanephrine results. It is surprising that it has not been described
      previously. Patients being assessed for catecholamine secreting tumours should be
      advised to withdraw from eating Indian foods at least 24 h prior to commencement
      of urinary collection.

PMID- 24084692
TI  - miR-25 and miR-92a regulate insulin I biosynthesis in rats.
AB  - The 3' UTR of insulin has been identified as a critical region that confers mRNA
      stability, which is crucial for promoting transcription in response to glucose
      challenge. miRNAs are endogenously encoded non-coding RNAs that function as
      regulators of gene expression. This regulatory function is generally mediated by
      complementary binding to the 3'UTR of its mRNA targets that affects subsequent
      translational process. Genes involved in the regulation of glucose homeostasis,
      particularly in insulin production, have been found as targets of several miRNAs.
      Yet, no direct miRNA-based regulators of insulin biosynthesis have been
      identified. In this study, identification of possible miRNA-based regulators of
      insulin production is explored. Members of a miRNA family, miR-25 and miR-92a,
      are found as direct modulators of insulin expression. Overexpression of miR-25 or
      miR-92a reduced insulin expression while inhibition of miR-25 and miR-92a
      expression using corresponding antagomiRs promoted insulin expression and
      ultimately enhanced glucose-induced insulin secretion. Furthermore, suppression
      of insulin secretion by pre miR-9 could be attenuated by treatment with anti-miR
      25 or miR-92a. Interestingly, we found the binding site of miR-25 and miR-92a to
      overlap with that of PTBP1, an important RNA binding molecule that stabilizes
      insulin mRNA for translation. Despite the increase in PTBP1 protein in the
      pancreas of diabetic rats, we observed insulin expression to be reduced alongside
      upregulation of miR-25 and miR-92a, suggesting an intricate regulation of insulin
      (bio)synthesis at its mRNA level. 

PMID- 24084694
TI  - A rapid direct assay for the routine measurement of oestradiol and oestrone by
      liquid chromatography tandem mass spectrometry.
AB  - BACKGROUND: Liquid chromatography tandem mass spectrometry (LC-MS/MS) is rapidly
      becoming the technology of choice for measuring steroid hormones. We have
      developed a rapid LC-MS/MS assay for the routine analysis of serum oestradiol and
      oestrone. The assay uses a relatively small volume and has a rapid run time.
      METHODS: Supported liquid extraction was performed on 250 uL of sample using
      methyl tertiary butyl ether. The extract was dried and reconstituted with 100 uL
      of 40% methanol. Online automated solid phase extraction was performed on 75 uL
      of extract using C18 cartridges on a Waters OSM coupled to a Waters TQS mass
      spectrometer. Serum samples (n = 197) were analysed by LC-MS/MS and a commercial
      immunoassay. RESULTS: The lower limit of quantitation for oestradiol and oestrone
      was 10 and 6 pmol/L, respectively. The coefficient of variation (CV) of the assay
      for oestradiol and oestrone concentrations of 125 pmol/L was <7%. The assay had a
      CV of 10% at 22 pmol/L for oestradiol and 5% at 16 pmol/L for oestrone. The
      average recovery for oestradiol was 102% and oestrone was 106%. The comparison
      with a commercial immunoassay gave the following equation: Immunoassay = 0.94 *
      LC-MS/MS + 21 pmol/L. The run time was 4.5 min per sample. DISCUSSION: We have
      developed a rapid assay for the LC-MS/MS measurement of oestradiol and oestrone
      which does not require derivatization in the sample preparation. The assay is
      suitable for routine clinical use or for clinical trials. The assay demonstrated
      superior performance compared to immunoassays at lower concentrations making it
      more suitable for use in males and patients on aromatase inhibitors.

PMID- 24084695
TI  - Label-free route to rapid, nanoscale characterization of cellular structure and
      dynamics through opaque media.
AB  - We report a novel technique for label-free, rapid visualization of structure and
      dynamics of live cells with nanoscale sensitivity through traditionally opaque
      media. Specifically, by combining principles of near-infrared (NIR) spectroscopy
      and quantitative phase imaging, functional characterization of cellular structure
      and dynamics through silicon substrates is realized in our study. We demonstrate
      the efficacy of the new approach by full-field imaging of erythrocyte morphology
      in their native states with a nm path length sensitivity. Additionally, we
      observe dynamic variations of human embryonic kidney cells, through a silicon
      substrate, in response to hypotonic stimulation with ms temporal resolution that
      also provides unique insight into the underlying biophysical changes. The
      proposed technology is fundamentally suited for high-performance investigations
      of biological specimens and significantly expands the options for visualization
      in complex microfluidic devices fabricated on silicon. 

PMID- 24084696
TI  - MicroRNA-137 represses Klf4 and Tbx3 during differentiation of mouse embryonic
      stem cells.
AB  - MicroRNA-137 (miR-137) has been shown to play an important role in the
      differentiation of neural stem cells. Embryonic stem (ES) cells have the
      potential to differentiate into different cell types including neurons; however,
      the contribution of miR-137 in the maintenance and differentiation of ES cells
      remains unknown. Here, we show that miR-137 is mainly expressed in ES cells at
      the mitotic phase of the cell cycle and highly upregulated during
      differentiation. We identify that ES cell transcription factors, Klf4 and Tbx3,
      are downstream targets of miR-137, and we show that endogenous miR-137 represses
      the 3' untranslated regions of Klf4 and Tbx3. Transfection of ES cells with
      mature miR-137 RNA duplexes led to a significant reduction in cell proliferation
      and the expression of Klf4, Tbx3, and other self-renewal genes. Furthermore, we
      demonstrate that increased miR-137 expression accelerates differentiation of ES
      cells in vitro. Loss of miR-137 during ES cell differentiation significantly
      impeded neuronal gene expression and morphogenesis. Taken together, our results
      suggest that miR-137 regulates ES cell proliferation and differentiation by
      repressing the expression of downstream targets, including Klf4 and Tbx3. 

PMID- 24084697
TI  - [(11)C]5-HTP and microPET are not suitable for pharmacodynamic studies in the
      rodent brain.
AB  - The PET tracer [(11)C]5-hydroxytryptophan ([(11)C]5-HTP), which is converted to
      [(11)C]5-hydroxytryptamine ([(11)C]5-HT) by aromatic amino acid decarboxylase
      (AADC), is thought to measure 5-HT synthesis rates. But can we measure these
      synthesis rates by kinetic modeling of [(11)C]5-HTP in rat? Male rats were
      scanned with [(11)C]5-HTP (60 minutes) after different treatments. Scans included
      arterial blood sampling and metabolite analysis. 5-HT synthesis rates were
      calculated by a two-tissue compartment model (2TCM) with irreversible tracer
      trapping or Patlak analysis. Carbidopa (inhibitor peripheral AADC) dose
      dependently increased [(11)C]5-HTP brain uptake, but did not influence 2TCM
      parameters. Therefore, 10 mg/kg carbidopa was applied in all subsequent study
      groups. These groups included treatment with NSD 1015 (general AADC inhibitor) or
      p-chlorophenylalanine (PCPA, inhibitor of tryptophan hydroxylase, TPH). In
      addition, the effect of a low-tryptophan (Trp) diet was investigated. NSD 1015 or
      Trp depletion did not affect any model parameters, but PCPA reduced [(11)C]5-HTP
      uptake, and the k3. This was unexpected as NSD 1015 directly inhibits the enzyme
      converting [(11)C]5-HTP to [(11)C]5-HT, suggesting that trapping of radioactivity
      does not distinguish between parent tracer and its metabolites. As different
      results have been acquired in monkeys and humans, [(11)C]5-HTP-PET may be
      suitable for measuring 5-HT synthesis in primates, but not in rodents. 

PMID- 24084698
TI  - Hypothesis of lipid-phase-continuity proton transfer for aerobic ATP synthesis.
AB  - The basic processes harvesting chemical energy for life are driven by proton
      (H(+)) movements. These are accomplished by the mitochondrial redox complex V,
      integral membrane supramolecular aggregates, whose structure has recently been
      described by advanced studies. These did not identify classical aqueous pores. It
      was proposed that H(+) transfer for oxidative phosphorylation (OXPHOS) does not
      occur between aqueous sources and sinks, where an energy barrier would be
      insurmountable. This suggests a novel hypothesis for the proton transfer. A lipid
      phase-continuity H(+) transfer is proposed in which H(+) are always bound to
      phospholipid heads and cardiolipin, according to Mitchell's hypothesis of
      asymmetric vectorial H(+) diffusion. A phase separation is proposed among the
      proton flow, following an intramembrane pathway, and the ATP synthesis, occurring
      in the aqueous phase. This view reminiscent of Grotthus mechanism would better
      account for the distance among the Fo and F1 moieties of FoF1-ATP synthase, for
      its mechanical coupling, as well as the necessity of a lipid membrane. A unique
      active role for lipids in the evolution of life can be envisaged. Interestingly,
      this view would also be consistent with the evidence of an OXPHOS outside
      mitochondria also found in non-vesicular membranes, housing the redox complexes. 

PMID- 24084700
TI  - Assessing forelimb function after unilateral cervical SCI using novel tasks: limb
      step-alternation, postural instability and pasta handling.
AB  - Cervical spinal cord injury (cSCI) can cause devastating neurological deficits,
      including impairment or loss of upper limb and hand function. A majority of the
      spinal cord injuries in humans occur at the cervical levels. Therefore,
      developing cervical injury models and developing relevant and sensitive
      behavioral tests is of great importance. Here we describe the use of a newly
      developed forelimb step-alternation test after cervical spinal cord injury in
      rats. In addition, we describe two behavioral tests that have not been used after
      spinal cord injury: a postural instability test (PIT), and a pasta-handling test.
      All three behavioral tests are highly sensitive to injury and are easy to use.
      Therefore, we feel that these behavioral tests can be instrumental in
      investigating therapeutic strategies after cSCI. 

PMID- 24084699
TI  - Stroke-induced brain parenchymal injury drives blood-brain barrier early leakage
      kinetics: a combined in vivo/in vitro study.
AB  - The disappointing clinical outcomes of neuroprotectants challenge the relevance
      of preclinical stroke models and data in defining early cerebrovascular events as
      potential therapeutic targets. The kinetics of blood-brain barrier (BBB) leakage
      after reperfusion and the link with parenchymal lesion remain debated. By using
      in vivo and in vitro approaches, we conducted a kinetic analysis of BBB
      dysfunction during early reperfusion. After 60 minutes of middle cerebral artery
      occlusion followed by reperfusion times up to 24 hours in mice, a non-invasive
      magnetic resonance imaging method, through an original sequence of diffusion
      weighted imaging, determined brain water mobility in microvascular compartments
      (D*) apart from parenchymal compartments (apparent diffusion coefficient). An
      increase in D* found at 4 hours post reperfusion concurred with the onset of both
      Evans blue/Dextran extravasations and in vitro BBB opening under oxygen-glucose
      deprivation and reoxygenation (R). The BBB leakage coincided with an emerging
      cell death in brain tissue as well as in activated glial cells in vitro. The co
      culture of BBB endothelial and glial cells evidenced a recovery of endothelium
      tightness when glial cells were absent or non-injured during R. Preserving the
      ischemic brain parenchymal cells within 4 hours of reperfusion may improve
      therapeutic strategies for cerebrovascular protection against stroke. 

PMID- 24084701
TI  - Influence of psychosocial factors on self-care behaviors and glycemic control in
      Turkish patients with type 2 diabetes mellitus.
AB  - PURPOSE: The main purpose of this study was to investigate the direct and
      indirect effects of psychosocial factors on self-care behavior and glycemic
      control in Turkish patients with type 2 diabetes mellitus. METHOD: The study used
      a cross-sectional questionnaire survey design (N = 350). Data were collected
      using the Summary of Diabetes Self-Care Activities Scale and the Multidimensional
      Diabetes Questionnaire. The relationship between the study variables was analyzed
      using Pearson's correlation coefficient and structural equation modeling.
      RESULTS: Self-efficacy was associated with social support, outcome expectancies,
      perceived interference, educational level, and self-care and A1C. According to
      the structural equation model, self-efficacy was the predictor variable that
      influenced both self-care and glycemic control. CONCLUSIONS: Self-efficacy in
      achieving desired health outcomes was found to play a central role in Turkish
      patients. Although interventions are planned and implemented to achieve and
      maintain self-management in individuals with diabetes, strengthening psychosocial
      factors, particularly self-efficacy, may contribute to adjustment to disease and
      good glycemic control in the long term.

PMID- 24084702
TI  - Practices of traditional birth attendants in Sierra Leone and perceptions by
      mothers and health professionals familiar with their care.
AB  - STUDY PURPOSE: Describe practices of traditional birth attendants (TBAs) in
      assisting women in childbirth and the perceptions of TBAs by mothers and health
      professionals familiar with their work. METHODOLOGY: Qualitative design using
      focus groups conducted in urban and rural settings in Sierra Leone. Separate
      audiotaped focus groups conducted for each group of participants lasting between
      45 and 90 minutes. PARTICIPANTS: Purposive sample of 20 TBAs, 20 mothers, and 10
      health professionals who met the following criteria: (a) at least 18 years of
      age, (b) TBAs currently practicing, (c) mothers who delivered at least one child
      assisted by a TBA, and (d) health professionals currently practicing in the
      hospital and familiar with TBA practices. FINDINGS: TBAs are valued by mothers,
      health professionals, and the community because they provide accessible and
      affordable care to mothers who may otherwise have no access to health services.
      TBAs need training, supervision, and resources for effective referral of mothers.
      Systemic problems in the health care system create enormous barriers to effective
      care for mothers and children independent of TBA practices that contribute to
      high maternal and infant mortality rates. The study findings have implications on
      broad public policy in improving maternal and child health in the country.

PMID- 24084703
TI  - The Tangled Branches (Las Ramas Enredadas): sexual risk, substance abuse, and
      intimate partner violence among Hispanic men who have sex with men.
AB  - Hispanic men who have sex with men (MSM) experience a number of health
      disparities including high rates of HIV infection from high-risk sex, substance
      abuse, and intimate partner violence. Although some research is available to
      document the relationships of these health disparities in the literature, few
      studies have explored the intersection of these disparities and the factors that
      influence them. The purpose of this study was to explore the experiences that
      Hispanic MSM residing in South Florida have with high-risk sex, substance abuse,
      and intimate partner violence. Focus groups were conducted and analyzed using
      grounded theory methodology until data saturation was reached (n = 20). Two core
      categories with subcategories emerged from the data: The Roots of Risk (Los
      raices del riesgo) and The Tangled Branches (Las Ramas Enredadas). The results of
      the study provided some important clinical implications as well as directions for
      future research with Hispanic MSM. 

PMID- 24084704
TI  - Molecular imaging of prostate cancer with PET.
AB  - Molecular imaging is paving the way for precision and personalized medicine. In
      view of the significant biologic and clinical heterogeneity of prostate cancer,
      molecular imaging is expected to play an important role in the evaluation of this
      prevalent disease. The natural history of prostate cancer spans from an indolent
      localized process to biochemical relapse after radical treatment with curative
      intent to a lethal castrate-resistant metastatic disease. The ongoing unraveling
      of the complex tumor biology of prostate cancer uniquely positions molecular
      imaging with PET to contribute significantly to every clinical phase of prostate
      cancer evaluation. The purpose of this article was to provide a concise review of
      the current state of affairs and potential future developments in the diagnostic
      utility of PET in prostate cancer. 

PMID- 24084705
TI  - Comparison of response evaluation in patients with gastroenteropancreatic and
      thoracic neuroendocrine tumors after treatment with [177Lu-DOTA0,Tyr3]octreotate.
AB  - Response Evaluation Criteria In Solid Tumors (RECIST) (unidimensional), Southwest
      Oncology Group (SWOG) solid tumor response criteria (bidimensional), and their
      modified variants are commonly used in the tumor response assessment after
      treatment of gastroenteropancreatic and thoracic neuroendocrine tumors (NETs). In
      the current study, RECIST, SWOG criteria, modified RECIST (mRECIST), and modified
      SWOG (mSWOG) criteria were compared in patients with NETs treated with [(177)Lu
      DOTA(0),Tyr(3)]octreotate ((177)Lu-octreotate). METHODS: Two-hundred sixty-eight
      Dutch patients with NETs who had been treated with (177)Lu-octreotate between
      January 2000 and April 2007 were studied. CT or MR imaging scans were analyzed
      using RECIST, SWOG criteria, mRECIST, and mSWOG criteria (including the tumor
      response class minor response [decrease of 13%-30% for mRECIST and 25%-50% for
      mSWOG]). The outcomes were correlated with progression-free survival (PFS) and
      overall survival (OS). RESULTS: Eleven patients had an unknown tumor response and
      were excluded. The rates of objective response (OR) (complete response + partial
      response [+minor response for mRECIST/mSWOG]), stable disease, and progressive
      disease (PD) were 28%, 49%, and 24%, respectively, according to RECIST; 25%, 49%,
      and 26%, respectively, according to SWOG; 44%, 33%, and 24%, respectively,
      according to mRECIST; and 45%, 29%, and 26%, respectively, according to mSWOG. In
      patients who had OR, stable disease, or PD, the median PFS was 26-30, 27-34, and
      8 mo, respectively, with any of the 4 response criteria. In patients who had OR,
      stable disease, or PD, the median OS was 55-57, 56-74, and 11-12 mo,
      respectively, with any of the 4 response criteria. Subanalyses for patients who
      had progression before treatment start were comparable. CONCLUSION: Patients with
      PD as treatment outcome had significantly shorter PFS and OS than patients with
      an OR or stable disease with all 4 scoring systems. PFS and OS were comparable
      for patients with tumor regression and stable disease. The addition of the
      response class minor response did not improve the correlation with PFS and OS.
      The 4 scoring systems gave comparable results in terms of PFS and OS per
      categorized outcome.

PMID- 24084708
TI  - 2013 SNMMI Highlights Lecture: General clinical nuclear medicine: clinical
      SPECT/CT--time for a new standard of care.

PMID- 24084710
TI  - 2013 SNMMI Highlights Lecture: Cardiovascular sciences.

PMID- 24084711
TI  - Single-photon-level quantum image memory based on cold atomic ensembles.
AB  - A quantum memory is a key component for quantum networks, which will enable the
      distribution of quantum information. Its successful development requires storage
      of single-photon light. Encoding photons with spatial shape through higher
      dimensional states significantly increases their information-carrying capability
      and network capacity. However, constructing such quantum memories is challenging.
      Here we report the first experimental realization of a true single-photon
      carrying orbital angular momentum stored via electromagnetically induced
      transparency in a cold atomic ensemble. Our experiments show that the non
      classical pair correlation between trigger photon and retrieved photon is
      retained, and the spatial structure of input and retrieved photons exhibits
      strong similarity. More importantly, we demonstrate that single-photon coherence
      is preserved during storage. The ability to store spatial structure at the single
      photon level opens the possibility for high-dimensional quantum memories. 

PMID- 24084712
TI  - One minute, sub-one-watt photothermal tumor ablation using porphysomes, intrinsic
      multifunctional nanovesicles.
AB  - We recently developed porphysomes as intrinsically multifunctional nanovesicles.
      A photosensitizer, pyropheophorbide alpha, was conjugated to a phospholipid and
      then self-assembled to liposome-like spherical vesicles. Due to the extremely
      high density of porphyrin in the porphyrin-lipid bilayer, porphysomes generated
      large extinction coefficients, structure-dependent fluorescence self-quenching,
      and excellent photothermal efficacy. In our formulation, porphysomes were
      synthesized using high pressure extrusion, and displayed a mean particle size
      around 120 nm. Twenty-four hr post-intravenous injection of porphysomes, the
      local temperature of the tumor increased from 30  degrees C to 62  degrees C
      rapidly upon one minute exposure of 750 mW (1.18 W/cm(2)), 671 nm laser
      irradiation. Following the complete thermal ablation of the tumor, eschars formed
      and healed within 2 weeks, while in the control groups the tumors continued to
      grow and all reached the defined end point within 3 weeks. These data show how
      porphysomes can be used as potent photothermal therapy (PTT) agents. 

PMID- 24084713
TI  - Regulation of MIR genes in response to abiotic stress in Hevea brasiliensis.
AB  - Increasing demand for natural rubber (NR) calls for an increase in latex yield
      and also an extension of rubber plantations in marginal zones. Both harvesting
      and abiotic stresses lead to tapping panel dryness through the production of
      reactive oxygen species. Many microRNAs regulated during abiotic stress modulate
      growth and development. The objective of this paper was to study the regulation
      of microRNAs in response to different types of abiotic stress and hormone
      treatments in Hevea. Regulation of MIR genes differs depending on the tissue and
      abiotic stress applied. A negative co-regulation between HbMIR398b with its
      chloroplastic HbCuZnSOD target messenger is observed in response to salinity. The
      involvement of MIR gene regulation during latex harvesting and tapping panel
      dryness (TPD) occurrence is further discussed. 

PMID- 24084714
TI  - Histone deacetylase inhibition downregulates collagen 3A1 in fibrotic lung
      fibroblasts.
AB  - Idiopathic pulmonary fibrosis (IPF) is a deadly disease characterized by chronic
      inflammation and excessive collagen accumulation in the lung. Myofibroblasts are
      the primary collagen-producing cells in pulmonary fibrosis. Histone deacetylase
      inhibitor (HDACi) can affect gene expression, and some, such as suberoylanilide
      hydroxamic acid (SAHA), are US FDA approved for cancer treatment. In this study,
      we investigated SAHA's effects on the expression of collagen III alpha 1 (COL3A1)
      in primary human IPF fibroblasts and in a murine model of pulmonary fibrosis. We
      observed that increased COL3A1 expression in IPF fibroblasts can be substantially
      reduced by SAHA treatment at the level of transcription as detected by RT-PCR;
      collagen III protein level was also reduced, as detected by Western blots and
      immunofluorescence. The deacetylation inhibitor effect of SAHA was verified by
      observing higher acetylation levels of both histone H3 and H4 in treated IPF
      cells. Chromatin immunoprecipitation (ChIP) experiments demonstrated that the
      reduced expression of COL3A1 by SAHA is with increased association of the
      repressive chromatin marker, H3K27Me3, and decreased association of the active
      chromatin marker, H3K9Ac. In our murine model of bleomycin-induced pulmonary
      fibrosis, the SAHA treated group demonstrated significantly less collagen III, as
      detected by immunohistochemistry. Our data indicate that the HDACi SAHA alters
      the chromatin associated with COL3A1, resulting in its decreased expression. 

PMID- 24084715
TI  - A combination of pre- and post-exposure ascorbic acid rescues mice from radiation
      induced lethal gastrointestinal damage.
AB  - The development of an effective therapy for radiation-induced gastrointestinal
      damage is important, because it is currently a major complication of treatment
      and there are few effective therapies available. Although we have recently
      demonstrated that pretreatment with ascorbic acid attenuates lethal
      gastrointestinal damage in irradiated mice, more than half of mice eventually
      died, thus indicating that better approach was needed. We then investigated a
      more effective therapy for radiation-induced gastrointestinal damage. Mice
      receiving abdominal radiation at 13 Gy were orally administered ascorbic acid
      (250 mg/kg/day) for three days before radiation (pretreatment), one shot of
      engulfment (250 mg/kg) at 8 h before radiation, or were administered the agent
      for seven days after radiation (post-treatment). None of the control mice
      survived the abdominal radiation at 13 Gy due to severe gastrointestinal damage
      (without bone marrow damage). Neither pretreatment with ascorbic acid (20%
      survival), engulfment (20%), nor post-treatment (0%) was effective in irradiated
      mice. However, combination therapy using ascorbic acid, including pretreatment,
      engulfment and post-treatment, rescued all of the mice from lethal abdominal
      radiation, and was accompanied by remarkable improvements in the gastrointestinal
      damage (100% survival). Omitting post-treatment from the combination therapy with
      ascorbic acid markedly reduced the mouse survival (20% survival), suggesting the
      importance of post-treatment with ascorbic acid. Combination therapy with
      ascorbic acid may be a potent therapeutic tool for radiation-induced
      gastrointestinal damage. 

PMID- 24084716
TI  - Chitosan-coated magnetic nanoparticles prepared in one step by reverse
      microemulsion precipitation.
AB  - Chitosan-coated magnetic nanoparticles (CMNP) were obtained at 70  degrees C and
      80  degrees C in a one-step method, which comprises precipitation in reverse
      microemulsion in the presence of low chitosan concentration in the aqueous phase.
      X-ray diffractometry showed that CMNP obtained at both temperatures contain a
      mixture of magnetite and maghemite nanoparticles with ~4.5 nm in average
      diameter, determined by electron microscopy, which suggests that precipitation
      temperature does not affect the particle size. The chitosan coating on
      nanoparticles was inferred from Fourier transform infrared spectrometry
      measurements; furthermore, the carbon concentration in the nanoparticles allowed
      an estimation of chitosan content in CMNP of 6%-7%. CMNP exhibit a
      superparamagnetic behavior with relatively high final magnetization values (~49
      53 emu/g) at 20 kOe and room temperature, probably due to a higher magnetite
      content in the mixture of magnetic nanoparticles. In addition, a slight direct
      effect of precipitation temperature on magnetization was identified, which was
      ascribed to a possible higher degree of nanoparticles crystallinity as
      temperature at which they are obtained increases. Tested for Pb2+ removal from a
      Pb(NO3)2 aqueous solution, CMNP showed a recovery efficacy of 100%, which makes
      them attractive for using in heavy metals ion removal from waste water. 

PMID- 24084717
TI  - Advanced knowledge of three important classes of grape phenolics: anthocyanins,
      stilbenes and flavonols.
AB  - Grape is qualitatively and quantitatively very rich in polyphenols. In
      particular, anthocyanins, flavonols and stilbene derivatives play very important
      roles in plant metabolism, thanks to their peculiar characteristics. Anthocyanins
      are responsible for the color of red grapes and wines and confer organoleptic
      characteristics on the wine. They are used for chemotaxonomic studies and to
      evaluate the polyphenolic ripening stage of grape. They are natural colorants,
      have antioxidant, antimicrobial and anticarcinogenic activity, exert protective
      effects on the human cardiovascular system, and are used in the food and
      pharmaceutical industries. Stilbenes are vine phytoalexins present in grape
      berries and associated with the beneficial effects of drinking wine. The
      principal stilbene, resveratrol, is characterized by anticancer, antioxidant,
      anti-inflammatory and cardioprotective activity. Resveratrol dimers and oligomers
      also occur in grape, and are synthetized by the vine as active defenses against
      exogenous attack, or produced by extracellular enzymes released from pathogens in
      an attempt to eliminate undesirable toxic compounds. Flavonols are a ubiquitous
      class of flavonoids with photo-protection and copigmentation (together with
      anthocyanins) functions. The lack of expression of the enzyme flavonoid 3',5'
      hydroxylase in white grapes restricts the presence of these compounds to
      quercetin, kaempferol and isorhamnetin derivatives, whereas red grapes usually
      also contain myricetin, laricitrin and syringetin derivatives. In the last ten
      years, the technological development of analytical instrumentation, particularly
      mass spectrometry, has led to great improvements and further knowledge of the
      chemistry of these compounds. In this review, the biosynthesis and biological
      role of these grape polyphenols are briefly introduced, together with the latest
      knowledge of their chemistry. 

PMID- 24084718
TI  - BTG1 expression correlates with the pathogenesis and progression of ovarian
      carcinomas.
AB  - BTG (B-cell translocation gene) can inhibit cell proliferation, metastasis, and
      angiogenesis and regulate cell cycle progression and differentiation in a variety
      of cell types. We aimed to clarify the role of BTG1 in ovarian carcinogenesis and
      progression. A BTG1-expressing plasmid was transfected into ovarian carcinoma
      cells and their phenotypes and related proteins were examined. BTG1 mRNA
      expression was detected in ovarian normal tissue (n = 17), ovarian benign tumors
      (n = 12), and ovarian carcinoma (n = 64) using real-time RT-PCR. Ectopic BTG1
      expression resulted in lower growth rate, high cisplatin sensitivity, G1 arrest,
      apoptosis, and decreased migration and invasion. Phosphoinositide 3-kinase,
      protein kinase B, Bcl-xL, survivin, vascular endothelial growth factor, and
      matrix metalloproteinase-2 mRNA and protein expression was reduced in
      transfectants as compared to control cells. There was higher expression of BTG1
      mRNA in normal tissue than in carcinoma tissue (p = 0.001) and in benign tumors
      than in carcinoma tissue (p = 0.027). BTG1 mRNA expression in International
      Federation of Gynecology and Obstetrics (FIGO) stage I/II ovarian carcinomas was
      higher than that in FIGO stage III/IV ovarian carcinomas (p = 0.038). Altered
      BTG1 expression might play a role in the pathogenesis and progression of ovarian
      carcinoma by modulating proliferation, migration, invasion, the cell cycle, and
      apoptosis. 

PMID- 24084719
TI  - Non-coding RNAs in muscle dystrophies.
AB  - ncRNAs are the most recently identified class of regulatory RNAs with vital
      functions in gene expression regulation and cell development. Among the variety
      of roles they play, their involvement in human diseases has opened new avenues of
      research towards the discovery and development of novel therapeutic approaches.
      Important data come from the field of hereditary muscle dystrophies, like
      Duchenne muscle dystrophy and Myotonic dystrophies, rare diseases affecting 1 in
      7000-15,000 newborns and is characterized by severe to mild muscle weakness
      associated with cardiac involvement. Novel therapeutic approaches are now ongoing
      for these diseases, also based on splicing modulation. In this review we provide
      an overview about ncRNAs and their behavior in muscular dystrophy and explore
      their links with diagnosis, prognosis and treatments, highlighting the role of
      regulatory RNAs in these pathologies. 

PMID- 24084721
TI  - A computational drug metabolite detection using the stable isotopic mass-shift
      filtering with high resolution mass spectrometry in pioglitazone and
      flurbiprofen.
AB  - The identification of metabolites in drug discovery is important. At present,
      radioisotopes and mass spectrometry are both widely used. However, rapid and
      comprehensive identification is still laborious and difficult. In this study, we
      developed new analytical software and employed a stable isotope as a tool to
      identify drug metabolites using mass spectrometry. A deuterium-labeled compound
      and non-labeled compound were both metabolized in human liver microsomes and
      analyzed by liquid chromatography/time-of-flight mass spectrometry (LC-TOF-MS).
      We computationally aligned two different MS data sets and filtered ions having a
      specific mass-shift equal to masses of labeled isotopes between those data using
      our own software. For pioglitazone and flurbiprofen, eight and four metabolites,
      respectively, were identified with calculations of mass and formulas and chemical
      structural fragmentation analysis. With high resolution MS, the approach became
      more accurate. The approach detected two unexpected metabolites in pioglitazone,
      i.e., the hydroxypropanamide form and the aldehyde hydrolysis form, which other
      approaches such as metabolite-biotransformation list matching and mass defect
      filtering could not detect. We demonstrated that the approach using computational
      alignment and stable isotopic mass-shift filtering has the ability to identify
      drug metabolites and is useful in drug discovery. 

PMID- 24084720
TI  - The COX-2 selective blocker etodolac inhibits TNFalpha-induced apoptosis in
      isolated rabbit articular chondrocytes.
AB  - Chondrocyte apoptosis contributes to the disruption of cartilage integrity in
      osteoarthritis (OA). Recently, we reported that activation of volume-sensitive Cl
      current (ICl,vol) mediates cell shrinkage, triggering apoptosis in rabbit
      articular chondrocytes. A cyclooxygenase (COX) blocker is frequently used for the
      treatment of OA. In the present study, we examined in vitro effects of selective
      blockers of COX on the TNFalpha-induced activation of ICl,vol in rabbit
      chondrocytes using the patch-clamp technique. Exposure of isolated chondrocytes
      to TNFalpha resulted in an obvious increase in membrane Cl- conductance. The
      TNFalpha-evoked Cl- current exhibited electrophysiological and pharmacological
      properties similar to those of ICl,vol. Pretreatment of cells with selective COX
      2 blocker etodolac markedly inhibited ICl,vol activation by TNFalpha as well as
      subsequent apoptotic events such as apoptotic cell volume decrease (AVD) and
      elevation of caspase-3/7 activity. In contrast, a COX-1 blocker had no effect on
      the decrease in cell volume or the increase in caspase-3/7 activity induced by
      TNFalpha. Thus, the COX-2-selective blocker had an inhibitory effect on TNFalpha
      induced apoptotic events, which suggests that this drug would have efficacy for
      the treatment of OA. 

PMID- 24084723
TI  - Preparation and characterization of nanoliposomes entrapping medium-chain fatty
      acids and vitamin C by lyophilization.
AB  - The complex nanoliposomes encapsulating both a hydrophilic drug vitamin C (vit C)
      and hydrophobic drug medium-chain fatty acids (MCFAs) was prepared by combining
      double emulsion method with dynamic high pressure microfluidization. The complex
      nanoliposomes was further freeze-dried under -86  degrees C for 48 h with sucrose
      at the sucrose/lipids ratio of 2:1(w/w) in order to enhance its stability. The
      freeze-dried complex nanoliposomes under the suitable conditions exhibited high
      entrapment efficiency of MCFAs (44.26 +/- 3.34)%, relatively high entrapment
      efficiency of vit C (62.25 +/- 3.43)%, low average size diameter (110.4 +/- 7.28)
      nm and good storage stability at 4  degrees C for 60 days with slight changes in
      mean particle diameter and drug entrapment efficiencies. The results of
      transmission electron microscopy of freeze-dried complex nanoliposomes also
      showed that the freeze-dried samples with sucrose were stable without great
      increase in their particle sizes and without destroying their spherical shape.
      The results indicated that sucrose presented well protection effects in MCFAs-vit
      C complex nanoliposomes, suggesting the possibility of further usage in
      commercial liposomes. 

PMID- 24084722
TI  - Carcinogenesis of pancreatic adenocarcinoma: precursor lesions.
AB  - Pancreatic adenocarcinoma displays a variety of molecular changes that evolve
      exponentially with time and lead cancer cells not only to survive, but also to
      invade the surrounding tissues and metastasise to distant sites. These changes
      include: genetic alterations in oncogenes and cancer suppressor genes; changes in
      the cell cycle and pathways leading to apoptosis; and also changes in epithelial
      to mesenchymal transition. The most common alterations involve the epidermal
      growth factor receptor (EGFR) gene, the HER2 gene, and the K-ras gene. In
      particular, the loss of function of tumor-suppressor genes has been documented in
      this tumor, especially in CDKN2a, p53, DPC4 and BRCA2 genes. However, other
      molecular events involved in pancreatic adenocarcinoma pathogenesis contribute to
      its development and maintenance, specifically epigenetic events. In fact, key
      tumor suppressors that are well established to play a role in pancreatic
      adenocarcinoma may be altered through hypermethylation, and oncogenes can be
      upregulated secondary to permissive histone modifications. Indeed, factors
      involved in tumor invasiveness can be aberrantly expressed through dysregulated
      microRNAs. This review summarizes current knowledge of pancreatic carcinogenesis
      from its initiation within a normal cell until the time that it has disseminated
      to distant organs. In this scenario, highlighting these molecular alterations
      could provide new clinical tools for early diagnosis and new effective therapies
      for this malignancy. 

PMID- 24084724
TI  - Generation of an ICF syndrome model by efficient genome editing of human induced
      pluripotent stem cells using the CRISPR system.
AB  - Genome manipulation of human induced pluripotent stem (iPS) cells is essential to
      achieve their full potential as tools for regenerative medicine. To date,
      however, gene targeting in human pluripotent stem cells (hPSCs) has proven to be
      extremely difficult. Recently, an efficient genome manipulation technology using
      the RNA-guided DNase Cas9, the clustered regularly interspaced short palindromic
      repeats (CRISPR) system, has been developed. Here we report the efficient
      generation of an iPS cell model for immunodeficiency, centromeric region
      instability, facial anomalies syndrome (ICF) syndrome using the CRISPR system. We
      obtained iPS cells with mutations in both alleles of DNA methyltransferase 3B
      (DNMT3B) in 63% of transfected clones. Our data suggest that the CRISPR system is
      highly efficient and useful for genome engineering of human iPS cells. 

PMID- 24084725
TI  - Relationship between serum osteocalcin levels and non-alcoholic fatty liver
      disease in adult males, South China.
AB  - AIM: To determine serum osteocalcin levels in South Chinese males with non
      alcoholic fatty liver disease (NAFLD) and to examine the relation between serum
      osteocalcin and NAFLD. METHODS: Data were collected from 1683 men attending the
      Fangchenggang Area Male Healthy and Examination Survey (FAMHES) from September
      2009 to December 2009. Serum osteocalcin was measured with
      electrochemiluminescence immunoassay. An abdominal ultrasonographic examination
      for all individuals was performed by two experienced ultrasonographers. The
      associations of serum osteocalcin with NAFLD were evaluated. RESULTS: The levels
      of serum osteocalcin were lower in 364 NAFLD participants than in 1319 non-NAFLD
      participants (24.51 +/- 1.38 ng/mL vs. 20.81 +/- 1.33 ng/mL, p < 0.001). Serum
      osteocalin level was associated with the scale of NAFLD (r = -0.150, p < 0.01).
      Serum osteocalin level tended to decrease with the scale of NAFLD. Binary
      logistic regression analysis showed that decreased ORs for NAFLD were observed
      from the first to the fourth osteocalcin quartiles. CONCLUSIONS: Our findings
      suggest that a lower serum osteocalcin level is associated with the presence of
      NAFLD.

PMID- 24084726
TI  - Achyranthes bidentata polypeptides reduces oxidative stress and exerts protective
      effects against myocardial ischemic/reperfusion injury in rats.
AB  - Achyranthes bidentata, a Chinese medicinal herb, is reported to be
      neuroprotective. However, its role in cardioprotection remains largely unknown.
      Our present study aimed to investigate the effects of Achyranthes bidentata
      polypeptides (ABPP) preconditioning on myocardial ischemia/reperfusion (MI/R)
      injury and to test the possible mechanisms. Rats were treated with ABPP (10
      mg/kg/d, i.p.) or saline once daily for one week. Afterward, all the animals were
      subjected to 30 min of myocardial ischemia followed by 4 h of reperfusion. ABPP
      preconditioning for one week significantly improved cardiac function following
      MI/R. Meanwhile, ABPP reduced infarct size, plasma creatine kinase (CK)/lactate
      dehydrogenase (LDH) activities and myocardial apoptosis at the end of reperfusion
      in rat hearts. Moreover, ABPP preconditioning significantly inhibited superoxide
      generation, gp91phox expression, malonaldialdehyde formation and enhanced
      superoxide dismutase activity in I/R hearts. Furthermore, ABPP treatment
      inhibited PTEN expression and increased Akt phosphorylation in I/R rat heart.
      PI3K inhibitor wortmannin blocked Akt activation, and abolished ABPP-stimulated
      anti-oxidant effect and cardioprotection. Our study demonstrated for the first
      time that ABPP reduces oxidative stress and exerts cardioprotection against MI/R
      injury in rats. Inhibition of PTEN and activation of Akt may contribute to the
      anti-oxidant capacity and cardioprotection of ABPP. 

PMID- 24084728
TI  - Cytokines, chaperones and neuroinflammatory responses in heroin-related death:
      what can we learn from different patterns of cellular expression?
AB  - Heroin (3,6-diacetylmorphine) has various effects on the central nervous system
      with several neuropathological alterations including hypoxic-ischemic brain
      damage from respiratory depressing effects and neuroinflammatory response. Both
      of these mechanisms induce the release of cytokines, chemokines and other
      inflammatory mediators by the activation of many cell types such as leucocytes
      and endothelial and glial cells, especially microglia, the predominant
      immunocompetent cell type within the central nervous system. The aim of this
      study is to clarify the correlation between intravenous heroin administration in
      heroin related death and the neuroinflammatory response. We selected 45 cases
      among autopsies executed for heroin-related death (358 total cases);
      immunohistochemical studies and Western blotting analyses were used to
      investigate the expression of brain markers such as tumor necrosis factor-alpha,
      oxygen-regulated protein 150, (interleukins) IL-1beta, IL-6, IL-8, IL-10, IL-15,
      cyclooxygenase-2, heat shock protein 70, and CD68 (MAC387). Findings demonstrated
      that morphine induces inflammatory response and cytokine release. In particular,
      oxygen-regulated protein 150, cyclooxygenase-2, heat shock protein 70, IL-6 and
      IL-15 cytokines were over-expressed with different patterns of cellular
      expression. 

PMID- 24084727
TI  - Interplay between cartilage and subchondral bone contributing to pathogenesis of
      osteoarthritis.
AB  - Osteoarthritis (OA) is a common debilitating joint disorder, affecting large
      sections of the population with significant disability and impaired quality of
      life. During OA, functional units of joints comprising cartilage and subchondral
      bone undergo uncontrolled catabolic and anabolic remodeling processes to adapt to
      local biochemical and biological signals. Changes in cartilage and subchondral
      bone are not merely secondary manifestations of OA but are active components of
      the disease, contributing to its severity. Increased vascularization and
      formation of microcracks in joints during OA have suggested the facilitation of
      molecules from cartilage to bone and vice versa. Observations from recent studies
      support the view that both cartilage and subchondral bone can communicate with
      each other through regulation of signaling pathways for joint homeostasis under
      pathological conditions. In this review we have tried to summarize the current
      knowledge on the major signaling pathways that could control the cartilage-bone
      biochemical unit in joints and participate in intercellular communication between
      cartilage and subchondral bone during the process of OA. An understanding of
      molecular communication that regulates the functional behavior of chondrocytes
      and osteoblasts in both physiological and pathological conditions may lead to
      development of more effective strategies for treating OA patients. 

PMID- 24084729
TI  - Development of nonalcoholic hepatopathy: contributions of oxidative stress and
      advanced glycation end products.
AB  - Advanced glycation end products (AGEs) are generated spontaneously in cells;
      however, under conditions of hyperglycemia and lipid peroxidation, their levels
      are higher than usual, which contribute to the development of diseases such as
      the nonalcoholic fatty liver disease (NAFLD). NAFLD is associated with oxidative
      stress (OS), which is linked to the transition of steatosis to steatohepatitis
      due to lipid peroxidation. The AGE-receptor interaction in hepatic stellate cells
      leads to an increase in reactive oxygen species and enhances the proliferation
      and activation of these cells, worsening liver fibrosis and disease progression.
      In this vicious cycle, there is production of (carboxymethyl)lysine, a biomarker
      for products of advanced glycation and lipid peroxidation, being a shared
      component between the two pathways. In this review, we aim to compile evidence to
      support the basic molecular mechanisms of AGEs and OS generation and their
      influence, independently or combined, on the evolution of NAFLD. The deeper
      understanding of the interrelations of AGEs + OS may help to elucidate the
      pathogenic pathways of NAFLD and to devise rational therapeutic interventions for
      this disease, with an expected positive impact on quality of life of patients. 

PMID- 24084730
TI  - Immunological mechanisms in the pathophysiology of non-alcoholic steatohepatitis.
AB  - Non-alcoholic steatohepatitis (NASH) is characterized by the presence of
      steatosis, inflammation and hepatocyte injury and constitutes hepatic
      manifestation of the metabolic syndrome. The pathogenesis of NASH is complex and
      implicates cross-talk between different metabolically active sites, such as liver
      and adipose tissue. Obesity is considered a chronic low-grade inflammatory state
      and the liver has been recognized as being an "immunological organ". The complex
      role of the immune system in the pathogenesis of NASH is currently raising great
      interest, also in view of the possible therapeutic potential of immunotherapy in
      NASH. This review focuses on the disturbances of the cells constituting the
      innate and adaptive immune system in the liver and in adipose tissue. 

PMID- 24084731
TI  - Radical roles for RAGE in the pathogenesis of oxidative stress in cardiovascular
      diseases and beyond.
AB  - Oxidative stress is a central mechanism by which the receptor for advanced
      glycation endproducts (RAGE) mediates its pathological effects. Multiple
      experimental inquiries in RAGE-expressing cultured cells have demonstrated that
      ligand-RAGE interaction mediates generation of reactive oxygen species (ROS) and
      consequent downstream signal transduction and regulation of gene expression. The
      primary mechanism by which RAGE generates oxidative stress is via activation of
      NADPH oxidase; amplification mechanisms in the mitochondria may further drive ROS
      production. Recent studies indicating that the cytoplasmic domain of RAGE binds
      to the formin mDia1 provide further support for the critical roles of this
      pathway in oxidative stress; mDia1 was required for activation of rac1 and NADPH
      oxidase in primary murine aortic smooth muscle cells treated with RAGE ligand
      S100B. In vivo, in multiple distinct disease models in animals, RAGE action
      generates oxidative stress and modulates cellular/tissue fate in range of
      disorders, such as in myocardial ischemia, atherosclerosis, and aneurysm
      formation. Blockade or genetic deletion of RAGE was shown to be protective in
      these settings. Indeed, beyond cardiovascular disease, evidence is accruing in
      human subjects linking levels of RAGE ligands and soluble RAGE to oxidative
      stress in disorders such as doxorubicin toxicity, acetaminophen toxicity,
      neurodegeneration, hyperlipidemia, diabetes, preeclampsia, rheumatoid arthritis
      and pulmonary fibrosis. Blockade of RAGE signal transduction may be a key
      strategy for the prevention of the deleterious consequences of oxidative stress,
      particularly in chronic disease. 

PMID- 24084732
TI  - Inhibiting invasion into human bladder carcinoma 5637 cells with diallyl
      trisulfide by inhibiting matrix metalloproteinase activities and tightening tight
      junctions.
AB  - Diallyl trisulfide (DATS), an organosulfur compound in garlic, possesses
      pronounced anti-cancer potential. However, the anti-invasive mechanism of this
      compound in human bladder carcinoma is not fully understood. In this study, we
      evaluated the anti-invasive effects of DATS on a human bladder carcinoma (5637)
      cell line and investigated the underlying mechanism. The results indicated that
      DATS suppressed migration and invasion of 5637 cells by reducing the activities
      and expression of matrix metalloproteinase (MMP)-2 and MMP-9 at both the protein
      and mRNA levels. DATS treatment up-regulated expression of tissue inhibitor of
      metalloproteinase (TIMP)-1 and TIMP-2 in 5637 cells. The inhibitory effects of
      DATS on invasiveness were associated with an increase in transepithelial
      electrical resistance and repression of the levels of claudin family members.
      Although further studies are needed, our data demonstrate that DATS exhibits anti
      invasive effects in 5637 cells by down-regulating the activity of tight junctions
      and MMPs. DATS may have future utility in clinical applications for treating
      bladder cancer. 

PMID- 24084733
TI  - Development of microsatellite markers in Pungtungia herzi using next-generation
      sequencing and cross-species amplification in the genus Pseudopungtungia.
AB  - Nuclear microsatellite markers for Pungtungia herzi were developed using a
      combination of next-generation sequencing and Sanger sequencing. One hundred
      primer sets in the flanking region of dinucleotide and trinucleotide repeat
      motifs were designed and tested for efficiency in polymerase chain reaction
      amplification. Of these primer sets, 16 new markers (16%) were successfully
      amplified with unambiguous polymorphic alleles in 16 individuals of Pungtungia
      herzi. Cross-species amplification with these markers was then examined in two
      related species, Pseudopungtungia nigra and Pseudopungtungia tenuicorpa. Fifteen
      and 11 primer pairs resulted in successful amplification in Pseudopungtungia
      nigra and Pseudopungtungia tenuicorpa, respectively, with various polymorphisms,
      ranging from one allele (monomorphic) to 11 alleles per marker. These results
      indicated that developing microsatellite markers for cross-amplification from a
      species that is abundant and phylogenetically close to the species of interest is
      a good alternative when tissue samples of an endangered species are insufficient
      to develop microsatellites. 

PMID- 24084735
TI  - Ras pathway inhibition prevents neovascularization by repressing endothelial cell
      sprouting.
AB  - Vascular networks develop from a growing vascular front that responds to VEGF and
      other guidance cues. Angiogenesis is required for normal tissue function, but,
      under conditions of stress, inappropriate vascularization can lead to disease.
      Therefore, inhibition of angiogenic sprouting may prevent neovascularization in
      patients with blinding neovascular eye diseases, including macular degeneration.
      VEGF antagonists have therapeutic benefits but also can elicit off-target
      effects. Here, we found that the Ras pathway, which functions downstream of a
      wide range of cytokines including VEGF, is active in the growing vascular front
      of developing and pathological vascular networks. The endogenous Ras inhibitor
      p120RasGAP was expressed predominately in quiescent VEGF-insensitive endothelial
      cells and was ectopically downregulated in multiple neovascular models. MicroRNA
      132 negatively regulated p120RasGAP expression. Experimental delivery of alpha
      miR-132 to developing mouse eyes disrupted tip cell Ras activity and prevented
      angiogenic sprouting. This strategy prevented ocular neovascularization in
      multiple rodent models even more potently than the VEGF antagonist, VEGF-trap.
      Targeting microRNA-132 as a therapeutic strategy may prove useful for treating
      multiple neovascular diseases of the eye and for preventing vision loss
      regardless of the neovascular stimulus.

PMID- 24084736
TI  - Divergence of IL-1, IL-18, and cell death  in NLRP3 inflammasomopathies.
AB  - The inflammasome is a cytoplasmic multiprotein complex that promotes
      proinflammatory cytokine maturation in response to host- and pathogen-derived
      signals. Missense mutations in cryopyrin (NLRP3) result in a hyperactive
      inflammasome that drives overproduction of the proinflammatory cytokines IL-1beta
      and IL-18, leading to the cryopyrin-associated periodic syndromes (CAPS) disease
      spectrum. Mouse lines harboring CAPS-associated mutations in Nlrp3 have elevated
      levels of IL-1beta and IL-18 and closely mimic human disease. To examine the role
      of inflammasome-driven IL-18 in murine CAPS, we bred Nlrp3 mutations onto an
      Il18r-null background. Deletion of Il18r resulted in partial phenotypic rescue
      that abolished skin and visceral disease in young mice and normalized serum
      cytokines to a greater extent than breeding to Il1r-null mice. Significant
      systemic inflammation developed in aging Nlrp3 mutant Il18r-null mice, indicating
      that IL-1 and IL-18 drive pathology at different stages of the disease process.
      Ongoing inflammation in double-cytokine knockout CAPS mice implicated a role for
      caspase-1-mediated pyroptosis and confirmed that CAPS is inflammasome dependent.
      Our results have important implications for patients with CAPS and residual
      disease, emphasizing the need to explore other NLRP3-mediated pathways and the
      potential for inflammasome-targeted therapy.

PMID- 24084737
TI  - Leptin regulation of Hsp60 impacts  hypothalamic insulin signaling.
AB  - Type 2 diabetes is characterized by insulin resistance and mitochondrial
      dysfunction in classical target tissues such as muscle, fat, and liver. Using a
      murine model of type 2 diabetes, we show that there is hypothalamic insulin
      resistance and mitochondrial dysfunction due to downregulation of the
      mitochondrial chaperone HSP60. HSP60 reduction in obese, diabetic mice was due to
      a lack of proper leptin signaling and was restored by leptin treatment. Knockdown
      of Hsp60 in a mouse hypothalamic cell line mimicked the mitochondrial dysfunction
      observed in diabetic mice and resulted in increased ROS production and insulin
      resistance, a phenotype that was reversed with antioxidant treatment. Mice with a
      heterozygous deletion of Hsp60 exhibited mitochondrial dysfunction and
      hypothalamic insulin resistance. Targeted acute downregulation of Hsp60 in the
      hypothalamus also induced insulin resistance, indicating that mitochondrial
      dysfunction can cause insulin resistance in the hypothalamus. Importantly, type 2
      diabetic patients exhibited decreased expression of HSP60 in the brain,
      indicating that this mechanism is relevant to human disease. These data indicate
      that leptin plays an important role in mitochondrial function and insulin
      sensitivity in the hypothalamus by regulating HSP60. Moreover, leptin/insulin
      crosstalk in the hypothalamus impacts energy homeostasis in obesity and insulin
      resistant states.

PMID- 24084738
TI  - FGF19 action in the brain induces  insulin-independent glucose lowering.
AB  - Insulin-independent glucose disposal (referred to as glucose effectiveness [GE])
      is crucial for glucose homeostasis and, until recently, was thought to be
      invariable. However, GE is reduced in type 2 diabetes and markedly decreased in
      leptin-deficient ob/ob mice. Strategies aimed at increasing GE should therefore
      be capable of improving glucose tolerance in these animals. The gut-derived
      hormone FGF19 has previously been shown to exert potent antidiabetic effects in
      ob/ob mice. In ob/ob mice, we found that systemic FGF19 administration improved
      glucose tolerance through its action in the brain and that a single, low-dose
      i.c.v. injection of FGF19 dramatically improved glucose intolerance within 2
      hours. Minimal model analysis of glucose and insulin data obtained during a
      frequently sampled i.v. glucose tolerance test showed that the antidiabetic
      effect of i.c.v. FGF19 was solely due to increased GE and not to changes of
      either insulin secretion or insulin sensitivity. The mechanism underlying this
      effect appears to involve increased metabolism of glucose to lactate. Together,
      these findings implicate the brain in the antidiabetic action of systemic FGF19
      and establish the brain's capacity to rapidly, potently, and selectively increase
      insulin-independent glucose disposal.

PMID- 24084739
TI  - MicroRNA-223 controls  susceptibility to tuberculosis by regulating  lung
      neutrophil recruitment.
AB  - The molecular mechanisms that control innate immune cell trafficking during
      chronic infection and inflammation, such as in tuberculosis (TB), are
      incompletely understood. During active TB, myeloid cells infiltrate the lung and
      sustain local inflammation. While the chemoattractants that orchestrate these
      processes are increasingly recognized, the posttranscriptional events that
      dictate their availability are unclear. We identified microRNA-223 (miR-223) as
      an upregulated small noncoding RNA in blood and lung parenchyma of TB patients
      and during murine TB. Deletion of miR-223 rendered TB-resistant mice highly
      susceptible to acute lung infection. The lethality of miR-223(-/-) mice was
      apparently not due to defects in antimycobacterial T cell responses. Exacerbated
      TB in miR-223(-/-) animals could be partially reversed by neutralization of
      CXCL2, CCL3, and IL-6, by mAb depletion of neutrophils, and by genetic deletion
      of Cxcr2. We found that miR-223 controlled lung recruitment of myeloid cells, and
      consequently, neutrophil-driven lethal inflammation. We conclude that miR-223
      directly targets the chemoattractants CXCL2, CCL3, and IL-6 in myeloid cells. Our
      study not only reveals an essential role for a single miRNA in TB, it also
      identifies new targets for, and assigns biological functions to, miR-223. By
      regulating leukocyte chemotaxis via chemoattractants, miR-223 is critical for the
      control of TB and potentially other chronic inflammatory diseases.

PMID- 24084742
TI  - A conversation with Aaron Ciechanover. Interview by Ushma S. Neill.

PMID- 24084741
TI  - Extracellular hemin crisis triggers acute  chest syndrome in sickle mice.
AB  - The prevention and treatment of acute chest syndrome (ACS) is a major clinical
      concern in sickle cell disease (SCD). However, the mechanism underlying the
      pathogenesis of ACS remains elusive. We tested the hypothesis that the hemolysis
      byproduct hemin elicits events that induce ACS. Infusion of a low dose of hemin
      caused acute intravascular hemolysis and autoamplification of extracellular hemin
      in transgenic sickle mice, but not in sickle-trait littermates. The sickle mice
      developed multiple symptoms typical of ACS and succumbed rapidly. Pharmacologic
      inhibition of TLR4 and hemopexin replacement therapy prior to hemin infusion
      protected sickle mice from developing ACS. Replication of the ACS-like phenotype
      in nonsickle mice revealed that the mechanism of lung injury due to extracellular
      hemin is independent of SCD. Using genetic and bone marrow chimeric tools, we
      confirmed that TLR4 expressed in nonhematopoietic vascular tissues mediated this
      lethal type of acute lung injury. Respiratory failure was averted after the onset
      of ACS-like symptoms in sickle mice by treating them with recombinant hemopexin.
      Our results reveal a mechanism that helps to explain the pathogenesis of ACS, and
      we provide proof of principle for therapeutic strategies to prevent and treat
      this condition in mice.

PMID- 24084740
TI  - NF-kappaB-mediated Pax7 dysregulation in the muscle microenvironment promotes
      cancer cachexia.
AB  - Cachexia is a debilitating condition characterized by extreme skeletal muscle
      wasting that contributes significantly to morbidity and mortality. Efforts to
      elucidate the underlying mechanisms of muscle loss have predominantly focused on
      events intrinsic to the myofiber. In contrast, less regard has been given to
      potential contributory factors outside the fiber within the muscle
      microenvironment. In tumor-bearing mice and patients with pancreatic cancer, we
      found that cachexia was associated with a type of muscle damage resulting in
      activation of both satellite and nonsatellite muscle progenitor cells. These
      muscle progenitors committed to a myogenic program, but were inhibited from
      completing differentiation by an event linked with persistent expression of the
      self-renewing factor Pax7. Overexpression of Pax7 was sufficient to induce
      atrophy in normal muscle, while under tumor conditions, the reduction of Pax7 or
      exogenous addition of its downstream target, MyoD, reversed wasting by restoring
      cell differentiation and fusion with injured fibers. Furthermore, Pax7 was
      induced by serum factors from cachectic mice and patients, in an NF-kappaB
      dependent manner, both in vitro and in vivo. Together, these results suggest that
      Pax7 responds to NF-kappaB by impairing the regenerative capacity of myogenic
      cells in the muscle microenvironment to drive muscle wasting in cancer.

PMID- 24084743
TI  - Pharmacological agents currently in clinical trials for disorders in
      neurogastroenterology.
AB  - Esophageal, gastrointestinal, and colonic diseases resulting from disorders of
      the motor and sensory functions represent almost half the patients presenting to
      gastroenterologists. There have been significant advances in understanding the
      mechanisms of these disorders, through basic and translational research, and in
      targeting the receptors or mediators involved, through clinical trials involving
      biomarkers and patient responses. These advances have led to relief of patients'
      symptoms and improved quality of life, although there are still significant unmet
      needs. This article reviews the pipeline of medications in development for
      esophageal sensorimotor disorders, gastroparesis, chronic diarrhea, chronic
      constipation (including opioid-induced constipation), and visceral pain. 

PMID- 24084745
TI  - P-glycoprotein ABCB1: a major player in drug handling by mammals.
AB  - Mammalian P-glycoproteins are active drug efflux transporters located in the
      plasma membrane. In the early nineties, we generated knockouts of the three P
      glycoprotein genes of mice, the Mdr1a, Mdr1b, and Mdr2 P-glycoproteins, now known
      as Abcb1a, Abcb1b, and Abcb4, respectively. In the JCI papers that are the
      subject of this Hindsight, we showed that loss of Mdr1a (Abcb1a) had a profound
      effect on the tissue distribution and especially the brain accumulation of a
      range of drugs frequently used in humans, including dexamethasone, digoxin,
      cyclosporin A, ondansetron, domperidone, and loperamide. All drugs were shown to
      be excellent substrates of the murine ABCB1A P-glycoprotein and its human
      counterpart, the MDR1 P-glycoprotein, ABCB1. We found that the ability of ABCB1
      to prevent accumulation of some drugs in the brain is a prerequisite for their
      clinical use, as absence of the transporter led to severe toxicity or undesired
      CNS pharmacodynamic effects. Subsequent work has fully confirmed the profound
      effect of the drug-transporting ABCB1 P-glycoprotein on the pharmacokinetics of
      drugs in humans. In fact, every new drug is now screened for transport by ABCB1,
      as this limits oral availability and penetration into sanctuaries protected by
      ABCB1, such as the brain. 

PMID- 24084749
TI  - Combination studies of platinum(II)-based metallointercalators with buthionine
      S,R-sulfoximine, 3-bromopyruvate, cisplatin or carboplatin.
AB  - With current chemotherapeutic treatment regimes often limited by adverse side
      effects, the synergistic combination of complexes with anticancer activity
      appears to offer a promising strategy for effective cancer treatment. This work
      investigates the anti-proliferative activity using a combination therapy approach
      where metallointercalators of the type [Pt(IL)(AL)](2+) (where IL is the
      intercalating ligand and AL is the ancillary ligand) are used in combination with
      currently approved anticancer drugs cisplatin and carboplatin and organic
      molecules buthionine-S,R-sulfoximine and 3-bromopyruvate. Synergistic
      relationships were observed, indicating a potential to decrease dose-dependent
      toxicity and improve therapeutic efficacy. 

PMID- 24084744
TI  - Emerging concepts in immunity to hepatitis C virus infection.
AB  - Since the discovery of hepatitis C virus (HCV) by molecular cloning almost a
      quarter of a century ago, unprecedented at the time because the virus had never
      been grown in cell culture or detected serologically, there have been impressive
      strides in many facets of our understanding of the natural history of the
      disease, the viral life cycle, the pathogenesis, and antiviral therapy. It is
      apparent that the virus has developed multiple strategies to evade immune
      surveillance and eradication. This Review covers what we currently understand of
      the temporal and spatial immunological changes within the human innate and
      adaptive host immune responses that ultimately determine the outcomes of HCV
      infection. 

PMID- 24084750
TI  - Long-term evolution and prognostic stratification of biopsy-proven active
      myocarditis.
AB  - BACKGROUND: Active myocarditis is characterized by large heterogeneity of
      clinical presentation and evolution. This study describes the characteristics and
      the long-term evolution of a large sample of patients with biopsy-proven active
      myocarditis, looking for accessible and valid early predictors of long-term
      prognosis. METHODS AND RESULTS: From 1981 to 2009, 82 patients with biopsy-proven
      active myocarditis were consecutively enrolled and followed-up for 147+/-107
      months. All patients underwent clinical and echocardiographic evaluation at
      baseline and at 6 months. At this time, improvement/normality of left ventricular
      ejection fraction (LVEF), defined as a LVEF increase > 20 percentage points or
      presence of LVEF>=50%, was assessed. At baseline, left ventricular dysfunction
      (LVEF<50%) and left atrium enlargement were independently associated with long
      term heart transplantation-free survival, regardless of the clinical pattern of
      disease onset. At 6 months, improvement/normality of LVEF was observed in 53% of
      patients. Persistence of New York Heart Association III to IV classes, left
      atrium enlargement, and improvement/normality of LVEF at 6 months emerged as
      independent predictors of long-term outcome. Notably, the short-term reevaluation
      showed a significant incremental prognostic value in comparison with the baseline
      evaluation (baseline model versus 6 months model: area under the curve 0.79
      versus 0.90, P=0.03). CONCLUSIONS: Baseline left ventricular function is a marker
      for prognosis regardless of the clinical pattern of disease onset, and its
      reassessment at 6 months appears useful for assessing longer-term outcome.

PMID- 24084751
TI  - TiO(2) nanotube arrays: intrinsic peroxidase mimetics.
AB  - TiO2 nanotube arrays (NTA), prepared by potentiostatic anodization, were
      discovered to possess an intrinsic peroxidase-like activity. The colorimetric and
      electrochemical assays both demonstrated their excellent catalytic activity
      towards H2O2 reduction. On this basis, a simple and inexpensive electrochemical
      biosensor for glucose detection was developed. 

PMID- 24084752
TI  - Dirac cones in two-dimensional systems: from hexagonal to square lattices.
AB  - The influence of lattice symmetry on the existence of Dirac cones was
      investigated for two distinct systems: a general two-dimensional (2D) atomic
      crystal containing two atoms in each unit cell and a 2D electron gas (2DEG) under
      a periodic muffin-tin potential. A criterion was derived under a tight-binding
      approximation for the existence of Dirac cones in the atomic crystal. When the
      transfer hoppings are assumed to be single functions of the distance between
      atoms, it was shown that the probability of observing Dirac cones in the atomic
      crystal gradually decreases before being reduced to zero when the lattice changes
      from hexagonal to square. For a 2DEG with full square symmetry, a Dirac point
      exists at the Brillouin zone corners, where the energy dispersion is parabolic
      not linear. These results suggest that conventional Dirac fermions (such as those
      in graphene) are difficult to achieve in a square lattice with full symmetry
      (wallpaper group p4mm). 

PMID- 24084753
TI  - Optimal copper supply is required for normal plant iron deficiency responses.
AB  - Iron (Fe) and copper (Cu) homeostasis are tightly linked across biology.
      Understanding crosstalk between Fe and Cu nutrition could lead to strategies for
      improved growth on soils with low or excess metals, with implications for
      agriculture and phytoremediation. Here, we show that Cu and Fe nutrition interact
      to increase or decrease Fe and/or Cu accumulation in leaves and Fe uptake
      processes. Leaf Cu concentration increased under low Fe supply, while high Cu
      lowered leaf Fe concentration. Ferric reductase activity, an indicator of Fe
      demand, was inhibited at insufficient or high Cu supply. Surprisingly, plants
      grown without Fe were more susceptible to Cu toxicity.

PMID- 24084754
TI  - Bottom-up catalytic approach towards nitrogen-enriched mesoporous carbons/sulfur
      composites for superior Li-S cathodes.
AB  - We demonstrate a sustainable and efficient approach to produce high performance
      sulfur/carbon composite cathodes via a bottom-up catalytic approach. The
      selective oxidation of H2S by a nitrogen-enriched mesoporous carbon catalyst can
      produce elemental sulfur as a by-product which in-situ deposit onto the carbon
      framework. Due to the metal-free catalytic characteristic and high catalytic
      selectivity, the resulting sulfur/carbon composites have almost no impurities
      that thus can be used as cathode materials with compromising battery performance.
      The layer-by-layer sulfur deposition allows atomic sulfur binding strongly with
      carbon framework, providing efficient immobilization of sulfur. The nitrogen
      atoms doped on the carbon framework can increase the surface interactions with
      polysulfides, leading to the improvement in the trapping of polysulfides. Thus,
      the composites exhibit a reversible capacity of 939 mAh g(-1) after 100 cycles at
      0.2 C and an excellent rate capability of 527 mAh g(-1) at 5 C after 70 cycles.

PMID- 24084755
TI  - Imaging InlC secretion to investigate cellular infection by the bacterial
      pathogen Listeria monocytogenes.
AB  - Bacterial intracellular pathogens can be conceived as molecular tools to dissect
      cellular signaling cascades due to their capacity to exquisitely manipulate and
      subvert cell functions which are required for the infection of host target
      tissues. Among these bacterial pathogens, Listeria monocytogenes is a Gram
      positive microorganism that has been used as a paradigm for intracellular
      parasitism in the characterization of cellular immune responses, and which has
      played instrumental roles in the discovery of molecular pathways controlling
      cytoskeletal and membrane trafficking dynamics. In this article, we describe a
      robust microscopical assay for the detection of late cellular infection stages of
      L. monocytogenes based on the fluorescent labeling of InlC, a secreted bacterial
      protein which accumulates in the cytoplasm of infected cells; this assay can be
      coupled to automated high-throughput small interfering RNA screens in order to
      characterize cellular signaling pathways involved in the up- or down-regulation
      of infection. 

PMID- 24084756
TI  - Exposure prediction approaches used in air pollution epidemiology studies: key
      findings and future recommendations.
AB  - Many epidemiologic studies of the health effects of exposure to ambient air
      pollution use measurements from central-site monitors as their exposure estimate.
      However, measurements from central-site monitors may lack the spatial and
      temporal resolution required to capture exposure variability in a study
      population, thus resulting in exposure error and biased estimates. Articles in
      this dedicated issue examine various approaches to predict or assign exposures to
      ambient pollutants. These methods include combining existing central-site
      pollution measurements with local- and/or regional-scale air quality models to
      create new or "hybrid" models for pollutant exposure estimates and using exposure
      models to account for factors such as infiltration of pollutants indoors and
      human activity patterns. Key findings from these articles are summarized to
      provide lessons learned and recommendations for additional research on improving
      exposure estimation approaches for future epidemiological studies. In summary,
      when compared with use of central-site monitoring data, the enhanced spatial
      resolution of air quality or exposure models can have an impact on resultant
      health effect estimates, especially for pollutants derived from local sources
      such as traffic (e.g., EC, CO, and NO(x)). In addition, the optimal exposure
      estimation approach also depends upon the epidemiological study design. We
      recommend that future research develops pollutant-specific infiltration data
      (including for PM species) and improves existing data on human time-activity
      patterns and exposure to local source (e.g., traffic), in order to enhance human
      exposure modeling estimates. We also recommend comparing how various approaches
      to exposure estimation characterize relationships between multiple pollutants in
      time and space and investigating the impact of improved exposure estimates in
      chronic health studies.

PMID- 24084757
TI  - A coupled sensor-spectrophotometric device for continuous measurement of
      formaldehyde in indoor environments.
AB  - Despite long-standing awareness of adverse health effects associated with chronic
      human exposure to formaldehyde, this hazardous air pollutant remains a challenge
      to measure in indoor environments. Traditional analytical techniques evaluate
      formaldehyde concentrations over several hours to several days in a single
      location in a residence, making it difficult to characterize daily temporal and
      spatial variation in human exposure to formaldehyde. There is a need for
      portable, easy-to-use devices that are specific and sensitive to gas-phase
      formaldehyde over short sampling periods so that dynamic processes governing
      formaldehyde fate, transport, and potential remediation in indoor environments
      may be studied more effectively. A recently developed device couples a chemical
      sensor element with spectrophotometric analysis for detection and quantification
      of part per billion (ppbv) gas-phase formaldehyde concentrations. This study
      established the ability of the coupled sensor-spectrophotometric device (CSSD) to
      report formaldehyde concentrations accurately and continuously on a 30-min
      sampling cycle at low ppbv concentrations previously untested for this device in
      a laboratory setting. Determination of the method detection limit (MDL), based on
      40 samples each at test concentrations of 5 and 10 ppbv, was found to be 1.9 and
      2.0 ppbv, respectively. Performance of the CSSD was compared with the
      dinitrophenylhydrazine (DNPH) derivatization method for formaldehyde
      concentrations ranging from 5-50 ppbv, and a linear relationship with a
      coefficient of determination of 0.983 was found between these two analytical
      techniques. The CSSD was also used to monitor indoor formaldehyde concentrations
      in two manufactured homes. During this time, formaldehyde concentrations varied
      from below detection limit to 65 ppbv and were above the US National Institute
      for Occupational Safety and Health (NIOSH) recommended exposure limit (REL) of 16
      ppbv, which is also the exposure limit value now adopted by the US Federal
      Emergency Management Agency (FEMA) to procure manufactured housing, 80% and 100%
      of the time, respectively. 

PMID- 24084759
TI  - Direct measurement of osmotic pressure via adaptive confinement of quasi hard
      disc colloids.
AB  - Confining a system in a small volume profoundly alters its behaviour. Hitherto,
      attention has focused on static confinement where the confining wall is fixed
      such as in porous media. However, adaptive confinement where the wall responds to
      the interior has clear relevance in biological systems. Here we investigate this
      phenomenon with a colloidal system of quasi hard discs confined by a ring of
      particles trapped in holographic optical tweezers, which form a flexible elastic
      wall. This elasticity leads to quasi-isobaric conditions within the confined
      region. By measuring the displacement of the tweezed particles, we obtain the
      radial osmotic pressure. We further find a novel bistable state of a hexagonal
      structure and concentrically layered fluid mimicking the shape of the
      confinement. The hexagonal configurations are found at lower pressure than those
      of the fluid, thus the bistability is driven by the higher entropy of disordered
      arrangements, unlike bulk hard systems. 

PMID- 24084758
TI  - Mapping the vertical distribution of population and particulate air pollution in
      a near-highway urban neighborhood: implications for exposure assessment.
AB  - Owing to data collection challenges, the vertical variation in population in
      cities and particulate air pollution are typically not accounted for in exposure
      assessments, which may lead to misclassification of exposures based on elevation
      of residency. To better assess this misclassification, the vertical distribution
      of the potentially highly exposed population (PHEP), defined as all residents
      within the 100-m buffer zone of above-ground highways or the 200-m buffer zone of
      a highway-tunnel exit, was estimated for four floor categories in Boston's
      Chinatown (MA, USA) using the three-dimensional digital geography methodology.
      Vertical profiles of particle number concentration (7-3000 nm; PNC) and
      particulate matter (PM2.5) mass concentration were measured by hoisting
      instruments up the vertical face of an 11-story (35-m) building near the study
      area throughout the day on multiple days. The concentrations from all the
      profiles (n=23) were averaged together for each floor category. As measurement
      elevation increased from 0 to 35 m PNC decreased by 7.7%, compared with 3.6% for
      PM2.5. PHEP was multiplied by the average PNC for each floor category to assess
      exposures for near-highway populations. The results show that adding temporally
      averaged vertical air pollution data had a small effect on residential ambient
      exposures for our study population; however, greater effects were observed when
      individual days were considered (e.g., winds were off the highways). 

PMID- 24084761
TI  - Explanations of sleep paralysis among Egyptian college students and the general
      population in Egypt and Denmark.
AB  - This cross-cultural study compared explanations of sleep paralysis (SP) in two
      countries and two groups with different levels of education in one country.
      Comparisons were made between individuals having experienced SP at least once in
      a lifetime from Cairo, Egypt (n = 89), Copenhagen, Denmark (n = 59), and the
      American University in Cairo, Egypt (n = 44). As hypothesized, participants from
      the general Egyptian population were more likely to endorse supernatural causal
      explanation of their SP compared to participants from Denmark; participants from
      the American University in Cairo were less likely to endorse supernatural causes
      of their SP compared to participants from the general Egyptian population.
      Moreover, participants from the American University in Cairo were marginally
      significantly more likely to endorse supernatural causes of their SP compared to
      participants from Denmark. Additionally, we explored which culturally bound
      explanations and beliefs about SP existed in Egypt and Denmark. We found that
      nearly half (48%) of the participants from the general Egyptian population
      believed their SP to be caused by the Jinn, a spirit-like creature with roots in
      Islamic tradition, which constitutes a culturally bound interpretation of the
      phenomenology of SP in this region of the world. Case studies are presented to
      illustrate these findings. 

PMID- 24084762
TI  - Intracellular co-delivery of zinc ions and plasmid DNA for enhancing gene
      transfection activity.
AB  - Zinc ions, methylated poly(1-vinylimidazole) (PVIm-Me) and plasmid DNA (pDNA)
      have formed ternary complexes for gene delivery. The resulting Zn-PVIm-Me-pDNA
      complexes have delivered both Zn(2+) ions and pDNA inside cells, leading to the
      nuclear translocation of the pDNA. By use of the pDNA containing a nuclear
      protein, NF-kappaB, binding sequence, the intracellular co-delivery of Zn(2+)
      ions and pDNA has enhanced gene expression. These results suggest that the
      intracellular Zn(2+) ions delivered by Zn-PVIm-Me-pDNA complexes activated the NF
      kappaB, enhancing the nuclear translocation of the pDNA. In conclusion, it has
      been demonstrated that the Zn-PVIm-Me-pDNA complex is capable of enhancing the
      gene transfection activity by a synergic effect of the PVIm-Me and the co
      delivered intracellular Zn(2+) ions. 

PMID- 24084764
TI  - A study of the decision outcomes and financial costs of multidisciplinary team
      meetings (MDMs) in oncology.
AB  - BACKGROUND: The benefits of multidisciplinary working in oncology are now
      accepted as the norm and widely accepted as being pivotal to the delivery of
      optimal cancer care. Central to this are the multidisciplinary meetings (MDMs)
      and we have evaluated decision outcomes and financial costs of these. METHODS: We
      reviewed the electronic patient records of 551 newly referred patients, discussed
      at 14 tumour site-specific MDMs for adult solid tumours and lymphoma (paediatric
      oncology and acute leukaemia were excluded) over a 1-month period, a total of 52
      MDMs were studied. In addition, the records of a further 81 patients from 10
      different MDMs were reviewed where the treating consultant had clearly recorded
      their opinion of how the patient should be managed and this was compared with the
      final MDM's consensus view. We also costed the MDMs utilising two different
      methodologies. RESULTS: The mean age of the 551 patients in the study was 62
      years. In all, 536 (97.3%) patients were treatment naive before MDM discussion
      and 15 (2.7%) had prior treatment. Median time to treatment after the MDM was 16
      days. In 535 (97.1%) cases, the MDM discussions were clearly documented, 16
      (2.9%) were not clearly documented. In total, 319 (57.9%) patients were discussed
      once, and 232 (42.1%) were re-discussed (one to six occasions). In 62 (12.7%)
      patients, there were delays in MDM discussion, 30 (48.4%) were related to
      radiology, 26 (41.9%) to histopathology and 6 (9.7%) a combination of both.
      Adherence to the MDM management plan decision occurred 503 times (91.3%) with 48
      (8.7%) deviations. In the smaller cohort of 81 patients, the consultant
      management plan and MDM consensus was compatible 71 (87.6%) times. On four
      occasions, there were major alterations in management while six were minor. The
      cost per month of our MDMs ranged from L2192 to L10 050 (median L5136) with total
      cost of L80 850 per month and the cost per new patient discussed was L415.
      CONCLUSION: Adherence to MDM decisions by health-care professionals occurs in the
      majority of patients. MDMs are costly, which may have relevance in the currently
      challenged health-care financial environment. There is a need to improve MDM
      efficiency without losing the considerable benefits associated with regular MDMs.

PMID- 24084765
TI  - Neutrophil to lymphocyte ratio may be predict of mortality in all conditions.

PMID- 24084766
TI  - Quantifying the natural history of breast cancer.
AB  - BACKGROUND: Natural history models of breast cancer progression provide an
      opportunity to evaluate and identify optimal screening scenarios. This paper
      describes a detailed Markov model characterising breast cancer tumour
      progression. METHODS: Breast cancer is modelled by a 13-state continuous-time
      Markov model. The model differentiates between indolent and aggressive ductal
      carcinomas in situ tumours, and aggressive tumours of different sizes. We
      compared such aggressive cancers, that is, which are non-indolent, to those which
      are non-growing and regressing. Model input parameters and structure were
      informed by the 1978-1984 Ostergotland county breast screening randomised
      controlled trial. Overlaid on the natural history model is the effect of
      screening on diagnosis. Parameters were estimated using Bayesian methods. Markov
      chain Monte Carlo integration was used to sample the resulting posterior
      distribution. RESULTS: The breast cancer incidence rate in the Ostergotland
      population was 21 (95% CI: 17-25) per 10 000 woman-years. Accounting for length
      biased sampling, an estimated 91% (95% CI: 85-97%) of breast cancers were
      aggressive. Larger tumours, 21-50 mm, had an average sojourn of 6 years (95% CI:
      3-16 years), whereas aggressive ductal carcinomas in situ took around half a
      month (95% CI: 0-1 month) to progress to the invasive <=10 mm state. CONCLUSION:
      These tumour progression rate estimates may facilitate future work analysing cost
      effectiveness and quality-adjusted life years for various screening strategies.

PMID- 24084763
TI  - Germline variants and advanced colorectal adenomas: adenoma prevention with
      celecoxib trial genome-wide association study.
AB  - PURPOSE: Identification of single-nucleotide polymorphisms (SNP) associated with
      development of advanced colorectal adenomas. EXPERIMENTAL DESIGN: Discovery
      phase: 1,406 Caucasian patients (139 advanced adenoma cases and 1,267 controls)
      from the Adenoma Prevention with Celecoxib (APC) trial were included in a genome
      wide association study (GWAS) to identify variants associated with
      postpolypectomy disease recurrence. Genome-wide significance was defined as false
      discovery rate less than 0.05, unadjusted P = 7.4 * 10(-7). Validation phase:
      results were further evaluated using 4,175 familial colorectal adenoma cases and
      5,036 controls from patients of European ancestry [COloRectal Gene Identification
      consortium (CORGI), Scotland, Australia, and VQ58]. RESULTS: Our study identified
      eight SNPs associated with advanced-adenoma risk in the APC trial (rs2837156,
      rs7278863, rs2837237, rs2837241, rs2837254, rs741864 at 21q22.2, and rs1381392
      and rs17651822 at 3p24.1, at P < 10(-7) level with OR > 2). Five variants in
      strong pairwise linkage disequilibrium (rs7278863, rs2837237, rs741864, rs741864,
      and rs2837241; r(2) = 0.8-1) are in or near the coding region for the tight
      junction adhesion protein, IGSF5. An additional variant associated with advanced
      adenomas, rs1535989 [minor allele frequency, 0.11; OR, 2.09; 95% confidence
      interval (CI), 1.50-2.91], also predicted colorectal cancer development in a
      validation analysis (P = 0.019) using a series of adenoma cases or colorectal
      cancer (CORGI study) and 3 sets of colorectal cancer cases and controls
      (Scotland, VQ58, and Australia; N = 9,211). CONCLUSIONS: Our results suggest that
      common polymorphisms contribute to the risk of developing advanced adenomas and
      might also contribute to the risk of developing colorectal cancer. The variant at
      rs1535989 may identify patients whose risk for neoplasia warrants increased
      colonoscopic surveillance.

PMID- 24084767
TI  - Early expression of the fractalkine receptor CX3CR1 in pancreatic carcinogenesis.
AB  - BACKGROUND: In pancreatic ductal adenocarcinoma (PDAC), fractalkine receptor
      CX3CR1 contributes to perineural invasion (PNI). We investigated whether CX3CR1
      expression occurs early in PDAC and correlates with tumour features other than
      PNI. METHODS: We studied CX3CR1 and CX3CL1 expression by immunohistochemistry in
      104 human PDAC and coexisting Pancreatic Intraepithelial Neoplasia (PanIN), and
      in PdxCre/LSL-Kras(G12D) mouse model of PDAC. CX3CR1 expression in vitro was
      studied by a spheroid model, and in vivo by syngenic mouse graft of tumour cells.
      RESULTS: In total, 56 (53.9%) PDAC expressed CX3CR1, 70 (67.3%) CX3CL1, and 45
      (43.3%) both. CX3CR1 expression was independently associated with tumour
      glandular differentiation (P=0.005) and PNI (P=0.01). Pancreatic Intraepithelial
      Neoplasias were more frequently CX3CR1+ (80.3%, P<0.001) and CX3CL1+ (86.8%,
      P=0.002) than matched cancers. The survival of PDAC patients was better in those
      with CX3CR1+ tumour (P=0.05). Mouse PanINs were also CX3CR1(+) and -CL1(+). In
      vitro, cytokines significantly increased CX3CL1 but not CX3CR1 expression.
      Differently, CX3CR1 was upregulated in tumour spheroids, and in vivo only in well
      differentiated tumours. CONCLUSION: Tumour differentiation, rather than
      inflammatory signalling, modulates CX3CR1 expression in PanINs and PDAC. CX3CR1
      expression pattern suggests its early involvement in PDAC progression, outlining
      a potential target for interfering with the PanIN transition to invasive cancer.

PMID- 24084769
TI  - Reply: comment on 'A derived neutrophil to lymphocyte ratio predicts clinical
      outcome in stage II and III colon cancer patients'.

PMID- 24084768
TI  - Aromatase inhibitor-induced modulation of breast density: clinical and genetic
      effects.
AB  - BACKGROUND: Change in breast density may predict outcome of women receiving
      adjuvant hormone therapy for breast cancer. We performed a prospective clinical
      trial to evaluate the impact of inherited variants in genes involved in oestrogen
      metabolism and signalling on change in mammographic percent density (MPD) with
      aromatase inhibitor (AI) therapy. METHODS: Postmenopausal women with breast
      cancer who were initiating adjuvant AI therapy were enrolled onto a multicentre,
      randomised clinical trial of exemestane vs letrozole, designed to identify
      associations between AI-induced change in MPD and single-nucleotide polymorphisms
      in candidate genes. Subjects underwent unilateral craniocaudal mammography before
      and following 24 months of treatment. RESULTS: Of the 503 enrolled subjects, 259
      had both paired mammograms at baseline and following 24 months of treatment and
      evaluable DNA. We observed a statistically significant decrease in mean MPD from
      17.1 to 15.1% (P<0.001), more pronounced in women with baseline MPD >=20%. No AI
      specific difference in change in MPD was identified. No significant associations
      between change in MPD and inherited genetic variants were observed. CONCLUSION:
      Subjects with higher baseline MPD had a greater average decrease in MPD with AI
      therapy. There does not appear to be a substantial effect of inherited variants
      in biologically selected candidate genes.

PMID- 24084770
TI  - Clinical-guide risk prediction of hepatocellular carcinoma development in chronic
      hepatitis C patients after interferon-based therapy.
AB  - BACKGROUND: Interferon (IFN)-based therapies could eradicate hepatitis C (HCV)
      and reduce the risk of hepatocellular carcinoma (HCC). However, HCC could still
      happen after sustained virological response (SVR). We aimed to develop a simple
      scoring system to predict the risk of HCC development among HCV patients after
      antiviral therapies. METHODS: From 1999 to 2009, 1879 patients with biopsy-proven
      HCV infection treated with IFN-based therapies were analyzed. RESULTS:
      Multivariable analysis showed old age (adjusted HR (aHR)=1.73, 95% CI=1.13-2.65
      for aged 60-69 and aHR=2.20, 95% CI=1.43-3.37 for aged >= 70), Male gender
      (aHR=1.74, 95% CI=1.26-2.41), platelet count <150 * 10(9)/l (HR=1.91, 95% CI=1.27
      2.86), alpha-fetoprotein >= 20 ng ml(-1) (HR=2.23, 95% CI=1.58-3.14), high
      fibrotic stage (HR=3.32, 95% CI=2.10-5.22), HCV genotype 1b (HR=1.53, 95% CI=1.10
      2.14), and non SVR (HR=2.40, 95% CI=1.70-3.38) were independent risk factors for
      HCC. Regression coefficients were used to build up a risk score and the accuracy
      was evaluated by using the area under the receiver operating characteristic curve
      (AUC). Three groups as low-, intermediate-, and high-risk are classified based on
      the risk scores. One hundred sixty patients (12.78%) in the derivation and 82
      patients (13.08%) in the validation cohort developed HCC with AUC of 79.4%,
      sensitivity of 84.38%, and specificity of 60.66%. In the validation cohort, the 5
      year HCC incidence was 1.81%, 12.92%, and 29.95% in low-, intermediate-, and high
      risk groups, with hazard ratios 4.49 in intermediate- and 16.14 in high-risk
      group respectively. The risk reduction of HCC is greatest in patients with SVR,
      with a 5-year and 10-year risk reduction of 28.91% and 27.99% respectively.
      CONCLUSION: The risk scoring system is accurate in predicting HCC development for
      HCV patients after antiviral therapies.

PMID- 24084771
TI  - Phase II study of dovitinib in patients with metastatic and/or unresectable
      gastrointestinal stromal tumours after failure of imatinib and sunitinib.
AB  - BACKGROUND: This prospective, phase II trial evaluated the efficacy and safety of
      dovitinib in patients with metastatic and/or unresectable gastrointestinal
      stromal tumours (GISTs) after failure of at least imatinib and sunitinib.
      METHODS: Patients received oral dovitinib, 500 mg once daily, for 5 consecutive
      days, followed by a 2-day rest, every 28 days. The primary endpoint was disease
      control rate (DCR; objective response+stable disease (SD)) at 24 weeks, assessed
      by computed tomography (CT) scan according to RECIST v1.0. Metabolic response was
      evaluated by positron emission tomography (PET)-CT scans performed at baseline
      and after 4 weeks of treatment. RESULTS: Between September 2011 and April 2012,
      30 patients were enrolled. DCR at 24 weeks by RECIST v1.0 was 13% and one patient
      (3%) had a partial response. Based on the European Organization for Research and
      Treatment of Cancer PET response criteria, four patients (13%) had a metabolic
      partial response after 4 weeks of treatment. At a median follow-up of 8.3 months
      (range, 6.3-12.2 months), median progression-free survival (PFS) was 3.6 months
      (95% confidence interval (CI), 3.5-3.7 months) and median overall survival was
      9.7 months (95% CI, 6.0-13.4 months). Metabolic progressive disease at Week 4 was
      significantly associated with shorter PFS (P=0.03). Grade 3/4 adverse events
      included asthenia (20%), neutropenia (13%), thrombocytopenia (10%), and
      hypertriglyceridaemia (10%). Most toxicities were manageable by dose
      modification. CONCLUSION: Dovitinib showed modest antitumour activity with
      manageable toxicities in heavily pretreated patients with advanced GISTs.

PMID- 24084772
TI  - Validation of the prognostic relevance of plasma C-reactive protein levels in
      soft-tissue sarcoma patients.
AB  - BACKGROUND: The concept of the involvement of systemic inflammation in cancer
      progression and metastases has gained attraction within the past decade. C
      reactive protein (CRP), a non-specific blood-based marker of the systemic
      inflammatory response, has been associated with decreased survival in several
      cancer types. The aim of the present study was to validate the prognostic value
      of pre-operative plasma CRP levels on clinical outcome in a large cohort of soft
      tissue sarcoma (STS) patients. METHODS: Three hundred and four STS patients,
      operated between 1998 and 2010, were retrospectively evaluated. CRP levels and
      the impact on cancer-specific survival (CSS), disease-free survival (DFS) and
      overall survival (OS) were assessed using Kaplan-Meier curves and univariate as
      well as multivariate Cox proportional models. Additionally, we developed a
      nomogram by supplementing the plasma CRP level to the well-established Kattan
      nomogram and evaluated the improvement of predictive accuracy of this novel
      nomogram by applying calibration and Harrell's concordance index (c-index).
      RESULTS: An elevated plasma CRP level was significantly associated with
      established prognostic factors, including age, tumour grade, size and depth
      (P<0.05). In multivariate analysis, increased CRP levels were significantly
      associated with a poor outcome for CSS (HR=2.05; 95% CI=1.13-3.74; P=0.019) and
      DFS (HR=1.88; 95% CI=1.07-3.34; P=0.029). The estimated c-index was 0.74 using
      the original Kattan nomogram and 0.77 when the plasma CRP level was added.
      CONCLUSION: An elevated pre-operative CRP level represents an independent
      prognostic factor that predicts poor prognosis and improves the predictive
      ability of the Kattan nomogram in STS patients. Our data suggest to further
      prospectively validate its potential utility for individual risk stratification
      and clinical management of STS patients.

PMID- 24084773
TI  - Cancer risk in patients with Hashimoto's thyroiditis: a nationwide cohort study.
AB  - BACKGROUND: This study examined the risk of cancer in patients with Hashimoto's
      thyroiditis (HT). METHODS: The Taiwanese National Health Insurance Research
      Database (NHIRD) was used to identify 1521 newly diagnosed HT patients from 1998
      2010, and 6084 frequency-matched non-HT patients. The risk of developing cancer
      for HT patients was measured using the Cox proportional hazard model. RESULTS:
      The incidence of developing cancer in the HT cohort was 5.07 per 1000 person
      years, which was 1.68-fold higher than that in the comparison cohort (P<0.001).
      Compared with patients aged 20-34 years, patients in older age groups had a
      higher risk of developing cancer (35-55 years: hazard ratio (HR)=5.96; >55 years:
      HR=9.66). After adjusting for sex, age, and comorbidities, the HT cohort had HRs
      of 4.76 and 11.8 for developing colorectal cancer and thyroid cancer,
      respectively, compared with non-HT cohort. Furthermore, the HT cohort to non-HT
      cohort incidence rate ratio (IRR) of thyroid cancer was higher in the first 3
      years (48.4, 95% confidence interval (CI)=35.0-66.3), with an adjusted HR of 49.4
      (95% CI=6.39-382.4). CONCLUSION: Hashimoto's thyroiditis patients have a higher
      risk of thyroid cancer and colorectal cancer. The thyroid cancer prevention
      effort should start soon after HT is diagnosed, while being cautious of
      colorectal cancer increases with time.

PMID- 24084774
TI  - A distorted honeycomb motif in divalent transition metal compounds based on 4
      phosphonbenzoic acid and exchange coupled Co(II) and Cu(II): synthesis,
      structural description and magnetic properties.
AB  - The first example of a two-dimensional inorganic hybrid material with cobalt as
      an open-shell transition metal ion and 4-phosphonbenzoic acid as a linker is
      presented together with its copper analogue. For both metal ions the inorganic
      part consists of edge-sharing metal-oxygen octahedra leading to a metal honeycomb
      motif. The magnetic properties of the cobalt compound are reported together with
      those of the corresponding copper compound based on the remarkably six
      coordinated copper(II) ions.

PMID- 24084776
TI  - An effective retro-cycloaddition of M3N@C80 (M = Sc, Lu, Ho)
      metallofulleropyrrolidines.
AB  - Sc3N@C80 fulleropyrrolidines are typical metallofullerene derivatives which were
      generated by the reaction of Sc3N@C80 with N-trityloxazolidinone. Here we report
      an effective retro-reaction of Sc3N@C80 fulleropyrrolidine by using 3
      chloroperoxybenzoic acid to give pristine Sc3N@C80 in a high yield. This
      technique is expected to be used for separating metallofullerenes (M3N@C80) from
      hollow fullerenes without HPLC. 

PMID- 24084777
TI  - The genomic distribution of sex-biased genes in drosophila serrata: X chromosome
      demasculinization, feminization, and hyperexpression in both sexes.
AB  - The chromosomal distribution of genes with sex-biased expression is often
      nonrandom, and in species with XY sex chromosome systems, it is common to observe
      a deficit of X-linked male-biased genes and an excess of X-linked female-biased
      genes. One explanation for this pattern is that sex-specific selection has shaped
      the gene content of the X. Alternatively, the deficit of male-biased and excess
      of female-biased genes could be an artifact of differences between the sexes in
      the global expression level of their X chromosome(s), perhaps brought about by a
      lack of dosage compensation in males and hyperexpression in females. In the
      montium fruit fly, Drosophila serrata, both these explanations can account for a
      deficit of male-biased and excess of female-biased X-linked genes. Using genome
      wide expression data from multiple male and female tissues (n = 176
      hybridizations), we found that testis- and accessory gland-specific genes are
      underrepresented whereas female ovary-specific genes are overrepresented on the X
      chromosome, suggesting that X-linkage is disfavored for male function genes but
      favored for female function genes. However, genes with such sex-specific
      functions did not fully account for the deficit of male-biased and excess of
      female-biased X-linked genes. We did, however, observe sex differences in the
      global expression level of the X chromosome and autosomes. Surprisingly, and in
      contrast to other species where a lack of dosage compensation in males is
      responsible, we found that hyperexpression of X-linked genes in both sexes leads
      to this imbalance in D. serrata. Our results highlight how common genomic
      distributions of sex-biased genes, even among closely related species, may arise
      via quite different evolutionary processes. 

PMID- 24084775
TI  - New targets for mucosal healing and therapy in inflammatory bowel diseases.
AB  - Healing of the inflamed mucosa (mucosal healing) is an emerging new goal for
      therapy and predicts clinical remission and resection-free survival in
      inflammatory bowel diseases (IBDs). The era of antitumor necrosis factor (TNF)
      antibody therapy was a remarkable progress in IBD therapy and anti-TNF agents led
      to mucosal healing in a subgroup of IBD patients; however, many patients do not
      respond to anti-TNF treatment highlighting the relevance of finding new targets
      for therapy of IBD. In particular, current studies are addressing the role of
      other anticytokine agents including antibodies against interleukin (IL)-6R, IL
      13, and IL-12/IL-23 as well as new anti-inflammatory concepts (regulatory T cell
      therapy, Smad7 antisense, Jak inhibition, Toll-like receptor 9 stimulation, worm
      eggs). In addition, blockade of T-cell homing via the integrins alpha4beta7 and
      the addressin mucosal vascular addressin cell adhesion molecule 1 (MAdCAM-1)
      emerges as a promising new approach for IBD therapy. Here, new approaches for
      achieving mucosal healing are discussed as well as their implications for future
      therapy of IBD. 

PMID- 24084779
TI  - Virtual hyperbolic metamaterials for manipulating radar signals in air.
AB  - Microwave beam transmission and manipulation in the atmosphere is an important
      but difficult task. One of the major challenges in transmitting and routing
      microwaves in air is unavoidable divergence because of diffraction. Here we
      introduce and design virtual hyperbolic metamaterials (VHMMs) formed by an array
      of plasma channels in air as a result of self-focusing of an intense laser pulse,
      and show that such structure can be used to manipulate microwave beams in air.
      Hyperbolic, or indefinite, metamaterials are photonic structures that possess
      permittivity and/or permeability tensor elements of opposite sign with respect to
      one another along principal axes, resulting in a strong anisotropy. Our proof-of
      concept results confirm that the proposed virtual hyperbolic metamaterial
      structure can be used for efficient beam collimation and for guiding radar
      signals around obstacles, opening a new paradigm for electromagnetic wave
      manipulation in air.

PMID- 24084778
TI  - The evolution and functional significance of nested gene structures in Drosophila
      melanogaster.
AB  - Nearly 10% of the genes in the genome of Drosophila melanogaster are in nested
      structures, in which one gene is completely nested within the intron of another
      gene (nested and including gene, respectively). Even though the coding sequences
      and untranslated regions of these nested/including gene pairs do not overlap,
      their intimate structures and the possibility of shared regulatory sequences
      raise questions about the evolutionary forces governing the origination and
      subsequent functional and evolutionary impacts of these structures. In this
      study, we show that nested genes experience weaker evolutionary constraint, have
      faster rates of protein evolution, and are expressed in fewer tissues than other
      genes, while including genes show the opposite patterns. Surprisingly, despite
      completely overlapping with each other, nested and including genes are less
      likely to display correlated gene expression and biological function than the
      nearby yet nonoverlapping genes. Interestingly, significantly fewer nested genes
      are transcribed from the same strand as the including gene. We found that same
      strand nested genes are more likely to be single-exon genes. In addition, same
      strand including genes are less likely to have known lethal or sterile phenotypes
      than opposite-strand including genes only when the corresponding nested genes
      have introns. These results support our hypothesis that selection against
      potential erroneous mRNA splicing when nested and including genes are on the same
      strand plays an important role in the evolution of nested gene structures. 

PMID- 24084780
TI  - One-step instant synthesis of protein-conjugated quantum dots at room
      temperature.
AB  - We present a new general facile strategy for the preparation of protein
      functionalized QDs in a single step at ambient conditions. We demonstrated that
      highly luminescent red to near-infrared (NIR) protein-functionalized QDs could be
      synthesized at room temperature in one second through a one-pot reaction that
      proceeds in aqueous solution. Herein protein-functionalized QDs were successfully
      constructed for a variety of proteins with a wide range of molecular weights and
      isoelectric points. The as-prepared protein-conjugated QDs exhibited high quantum
      yield, high photostabiliy and colloidal stability, and high functionalization
      efficiency. Importantly, the proteins attached to the QDs maintain their
      biological activities and are capable of catalyzing reactions and biotargeting.
      In particular, the as-prepared transferrin-QDs could be used to label cancer
      cells with high specificity. Moreover, we demonstrated that this synthetic
      strategy could be extended to prepare QDs functionalized with folic acids and
      peptides, which were also successfully applied to cancer cell imaging. 

PMID- 24084781
TI  - Chitosan nanoparticles attenuate hydrogen peroxide-induced stress injury in mouse
      macrophage RAW264.7 cells.
AB  - This study was carried out to investigate the protective effects of chitosan
      nanoparticles (CNP) against hydrogen peroxide (H2O2)-induced oxidative damage in
      murine macrophages RAW264.7 cells. After 24 h pre-incubation with CNP (25-200
      MUg/mL) and chitosan (CS) (50-200 MUg/mL, as controls), the viability loss in
      RAW264.7 cells induced by H2O2 (500 MUM) for 12 h was markedly restored in a
      concentration-dependent manner as measured by MTT assay (P < 0.05) and decreased
      in cellular LDH release (P < 0.05). Moreover, CNP also exerted preventive effects
      on suppressing the production of lipid peroxidation such as malondialdehyde (MDA)
      (P < 0.05), restoring activities of endogenous antioxidant including superoxide
      dismutase (SOD), and glutathione peroxidase (GSH-Px) (P < 0.05), along with
      increasing total antioxidant capacity (T-AOC) (P < 0.05). In addition, pre
      incubation of CNP with RAW264.7 cells for 24 h resulted in the increase of the
      gene expression level of endogenous antioxidant enzymes, such as MnSOD and GSH-Px
      (P < 0.05). At the same concentration, CNP significantly decreased LDH release
      and MDA (P < 0.05) as well as increased MnSOD, GSH-Px, and T-AOC activities (P <
      0.05) as compared to CS. Taken together, our findings suggest that CNP can more
      effectively protect RAW264.7 cells against oxidative stress by H2O2 as compared
      to CS, which might be used as a potential natural compound-based antioxidant in
      the functional food and pharmaceutical industries.

PMID- 24084782
TI  - Advances in the study of the structures and bioactivities of metabolites isolated
      from mangrove-derived fungi in the South China Sea.
AB  - Many metabolites with novel structures and biological activities have been
      isolated from the mangrove fungi in the South China Sea, such as
      anthracenediones, xyloketals, sesquiterpenoids, chromones, lactones, coumarins
      and isocoumarin derivatives, xanthones, and peroxides. Some compounds have
      anticancer, antibacterial, antifungal and antiviral properties, but the
      biosynthesis of these compounds is still limited. This review summarizes the
      advances in the study of secondary metabolites from the mangrove-derived fungi in
      the South China Sea, and their biological activities reported between 2008 and
      mid-2013. 

PMID- 24084783
TI  - Functional genomics of novel secondary metabolites from diverse cyanobacteria
      using untargeted metabolomics.
AB  - Mass spectrometry-based metabolomics has become a powerful tool for the detection
      of metabolites in complex biological systems and for the identification of novel
      metabolites. We previously identified a number of unexpected metabolites in the
      cyanobacterium Synechococcus sp. PCC 7002, such as histidine betaine, its
      derivatives and several unusual oligosaccharides. To test for the presence of
      these compounds and to assess the diversity of small polar metabolites in other
      cyanobacteria, we profiled cell extracts of nine strains representing much of the
      morphological and evolutionary diversification of this phylum. Spectral features
      in raw metabolite profiles obtained by normal phase liquid chromatography coupled
      to mass spectrometry (MS) were manually curated so that chemical formulae of
      metabolites could be assigned. For putative identification, retention times and
      MS/MS spectra were cross-referenced with those of standards or available
      sprectral library records. Overall, we detected 264 distinct metabolites. These
      included indeed different betaines, oligosaccharides as well as additional
      unidentified metabolites with chemical formulae not present in databases of
      metabolism. Some of these metabolites were detected only in a single strain, but
      some were present in more than one. Genomic interrogation of the strains revealed
      that generally, presence of a given metabolite corresponded well with the
      presence of its biosynthetic genes, if known. Our results show the potential of
      combining metabolite profiling and genomics for the identification of novel
      biosynthetic genes. 

PMID- 24084784
TI  - Antimicrobial peptides from marine proteobacteria.
AB  - After years of inadequate use and the emergence of multidrug resistant (MDR)
      strains, the efficiency of "classical" antibiotics has decreased significantly.
      New drugs to fight MDR strains are urgently needed. Bacteria hold much promise as
      a source of unusual bioactive metabolites. However, the potential of marine
      bacteria, except for Actinomycetes and Cyanobacteria, has been largely
      underexplored. In the past two decades, the structures of several antimicrobial
      compounds have been elucidated in marine Proteobacteria. Of these compounds,
      polyketides (PKs), synthesised by condensation of malonyl-coenzyme A and/or
      acetyl-coenzyme A, and non-ribosomal peptides (NRPs), obtained through the
      linkage of (unusual) amino acids, have recently generated particular interest.
      NRPs are good examples of naturally modified peptides. Here, we review and
      compile the data on the antimicrobial peptides isolated from marine
      Proteobacteria, especially NRPs. 

PMID- 24084785
TI  - Synthesis of marine alpha-methoxylated fatty acid analogs that effectively
      inhibit the topoisomerase IB from Leishmania donovani with a mechanism different
      from that of camptothecin.
AB  - Sponges biosynthesize alpha-methoxylated fatty acids with unusual biophysical and
      biological properties and in some cases they display enhanced anticancer
      activities. However, the antiprotozoal properties of the alpha-methoxylated fatty
      acids have been less studied. In this work, we describe the total synthesis of
      (5Z,9Z)-(+/-)-2-methoxy-5, 9-eicosadienoic acid (1) and its acetylenic analog (+/
      )-2-methoxy-5,9-eicosadiynoic acid (2), and report that they inhibit (EC50 values
      between 31 and 22 uM) the Leishmania donovani DNA topoisomerase IB enzyme
      (LdTopIB). The inhibition of LdTopIB (EC50 = 53 uM) by the acid (+/-)-2-methoxy-6
      icosynoic acid (12) was studied as well. The potency of LdTopIB inhibition
      followed the trend 2 > 1 > 12, indicating that the effectiveness of inhibition
      depends on the degree of unsaturation. All of the studied alpha-methoxylated
      fatty acids failed to inhibit the human topoisomerase IB enzyme (hTopIB) at 100
      uM. However, the alpha-methoxylated fatty acids were capable of inhibiting an
      active but truncated LdTopIB with which camptothecin (CPT) cannot interact
      suggesting that the methoxylated fatty acids inhibit LdTopIB with a mechanism
      different from that of CPT. The diunsaturated fatty acids displayed low
      cytotoxicity towards Leishmania infantum promastigotes (EC50 values between 260
      and 240 uM), but 12 displayed a better cytotoxicity towards Leishmania donovani
      promastigotes (EC50 = 100 uM) and a better therapeutic index.

PMID- 24084786
TI  - Evaluation of the in vitro anti-atherogenic properties of lipid fractions of
      olive pomace, olive pomace enriched fish feed and gilthead sea bream (Sparus
      aurata) fed with olive pomace enriched fish feed.
AB  - Given the pivotal role of Platelet-Activating-Factor (PAF) in atherosclerosis and
      the cardio-protective role of PAF-inhibitors derived from olive pomace, the
      inclusion of olive pomace in fish feed has been studied for gilthead sea bream
      (Sparus aurata). The aim of the current research was to elucidate the anti
      atherogenic properties of specific HPLC lipid fractions obtained from olive
      pomace, olive pomace enriched fish feed and fish fed with the olive pomace
      enriched fish feed, by evaluating their in vitro biological activity against
      washed rabbit platelets. This in vitro study underlines that olive pomace
      inclusion in fish feed improves the nutritional value of both fish feed and fish
      possibly by enriching the marine lipid profile of gilthead sea bream (Sparus
      aurata) with specific bioactive lipid compounds of plant origin. 

PMID- 24084788
TI  - Screening tests for the rapid detection of diarrhetic shellfish toxins in
      Washington State.
AB  - The illness of three people due to diarrhetic shellfish poisoning (DSP) following
      their ingestion of recreationally harvested mussels from Sequim Bay State Park in
      the summer of 2011, resulted in intensified monitoring for diarrhetic shellfish
      toxins (DSTs) in Washington State. Rapid testing at remote sites was proposed as
      a means to provide early warning of DST events in order to protect human health
      and allow growers to test "pre-harvest" shellfish samples, thereby preventing
      harvest of toxic product that would later be destroyed or recalled. Tissue
      homogenates from several shellfish species collected from two sites in Sequim
      Bay, WA in the summer 2012, as well as other sites throughout Puget Sound, were
      analyzed using three rapid screening methods: a lateral flow antibody-based test
      strip (Jellett Rapid Test), an enzyme-linked immunosorbent assay (ELISA) and a
      protein phosphatase 2A inhibition assay (PP2A). The results were compared to the
      standard regulatory method of liquid chromatography coupled with tandem mass
      spectroscopy (LC-MS/MS). The Jellett Rapid Test for DSP gave an unacceptable
      number of false negatives due to incomplete extraction of DSTs using the
      manufacturer's recommended method while the ELISA antibody had low cross
      reactivity with dinophysistoxin-1, the major toxin isomer in shellfish from the
      region. The PP2A test showed the greatest promise as a screening tool for
      Washington State shellfish harvesters. 

PMID- 24084787
TI  - Microcystin-LR and cylindrospermopsin induced alterations in chromatin
      organization of plant cells.
AB  - Cyanobacteria produce metabolites with diverse bioactivities, structures and
      pharmacological properties. The effects of microcystins (MCYs), a family of
      peptide type protein-phosphatase inhibitors and cylindrospermopsin (CYN), an
      alkaloid type of protein synthesis blocker will be discussed in this review. We
      are focusing mainly on cyanotoxin-induced changes of chromatin organization and
      their possible cellular mechanisms. The particularities of plant cells explain
      the importance of such studies. Preprophase bands (PPBs) are premitotic
      cytoskeletal structures important in the determination of plant cell division
      plane. Phragmoplasts are cytoskeletal structures involved in plant cytokinesis.
      Both cyanotoxins induce the formation of multipolar spindles and disrupted
      phragmoplasts, leading to abnormal sister chromatid segregation during mitosis.
      Thus, MCY and CYN are probably inducing alterations of chromosome number. MCY
      induces programmed cell death: chromatin condensation, nucleus fragmentation,
      necrosis, alterations of nuclease and protease enzyme activities and patterns.
      The above effects may be related to elevated reactive oxygen species (ROS) and/or
      disfunctioning of microtubule associated proteins. Specific effects: MCY-LR
      induces histone H3 hyperphosphorylation leading to incomplete chromatid
      segregation and the formation of micronuclei. CYN induces the formation of split
      or double PPB directly related to protein synthesis inhibition. Cyanotoxins are
      powerful tools in the study of plant cell organization. 

PMID- 24084789
TI  - Oxygenated ylangene-derived sesquiterpenoids from the soft coral Lemnalia
      philippinensis.
AB  - Chemical examination of a Taiwanese soft coral Lemnalia philippinensis led to the
      isolation of three oxygenated ylangene-derived sesquiterpenoids 1-3, including
      two new metabolites, philippinlins A and B (1 and 2). The structures of these
      compounds were elucidated on the basis of detailed spectroscopic data. Compound 1
      was shown to exhibit cytotoxicity against HepG2, MDA-MB231 and A549 cancer cell
      lines. 

PMID- 24084790
TI  - Composition and quantitation of microalgal lipids by ERETIC 1H NMR method.
AB  - Accurate characterization of biomass constituents is a crucial aspect of research
      in the biotechnological application of natural products. Here we report an
      efficient, fast and reproducible method for the identification and quantitation
      of fatty acids and complex lipids (triacylglycerols, glycolipids, phospholipids)
      in microalgae under investigation for the development of functional health
      products (probiotics, food ingredients, drugs, etc.) or third generation
      biofuels. The procedure consists of extraction of the biological matrix by
      modified Folch method and direct analysis of the resulting material by proton
      nuclear magnetic resonance (1H NMR). The protocol uses a reference electronic
      signal as external standard (ERETIC method) and allows assessment of total lipid
      content, saturation degree and class distribution in both high throughput
      screening of algal collection and metabolic analysis during genetic or culturing
      studies. As proof of concept, the methodology was applied to the analysis of
      three microalgal species (Thalassiosira weissflogii, Cyclotella cryptica and
      Nannochloropsis salina) which drastically differ for the qualitative and
      quantitative composition of their fatty acid-based lipids.

PMID- 24084791
TI  - The red seaweed Gracilaria gracilis as a multi products source.
AB  - In recent years seaweeds have increasingly attracted interest in the search for
      new drugs and have been shown to be a primary source of bioactive natural
      compounds and biomaterials. In the present investigation, the biochemical
      composition of the red seaweed Gracilaria gracilis, collected seasonally in the
      Lesina Lagoon (Southern Adriatic Sea, Lesina, Italy), was assayed by means of
      advanced analytical techniques, such as gas-chromatography coupled with mass
      spectrometry and spectrophotometric tests. In particular, analysis of lipids,
      fatty acids, sterols, proteins, phycobiliproteins and carbohydrates as well as
      phenolic content, antioxidant and radical scavenging activity were performed. In
      winter extracts of G. gracilis, a high content of R-phycoerythrin together with
      other valuable products such as arachidonic acid (PUFA omega-6), proteins and
      carbohydrates was observed. High antioxidant and radical scavenging activities
      were also detected in summer extracts of the seaweed together with a high content
      of total phenols. In conclusion, this study points out the possibility of using
      Gracilaria gracilis as a multi products source for biotechnological,
      nutraceutical and pharmaceutical applications even although more investigations
      are required for separating, purifying and characterizing these bioactive
      compounds. 

PMID- 24084792
TI  - Evidencing the mask effect of graphene oxide: a comparative study on primary
      human and murine phagocytic cells.
AB  - Graphene oxide (GO) is attracting an ever-growing interest in different fields
      and applications. Not much is known about the possible impact of GO sheet lateral
      dimensions on their effects in vitro, especially on human primary cells. In an
      attempt to address this issue, we present a study to evaluate, how highly soluble
      2-dimensional GO constituted of large or small flakes affects human monocyte
      derived macrophages (hMDM). For this purpose, the lateral size of GO was tuned
      using sonication and three samples were obtained. The non sonicated one presented
      large flakes (~1.32 MUm) while sonication for 2 and 26 hours generated small
      (~0.27 MUm) and very small (~0.13 MUm) sheets of GO, respectively. Cell studies
      were then conducted to evaluate the cytotoxicity, the oxidative stress induction,
      the activation potential and the pro-inflammatory effects of these different
      types of GO at increasing concentrations. In comparison, the same experiments
      were run on murine intraperitoneal macrophages (mIPM). The interaction between GO
      and cells was further examined by TEM and Raman spectroscopy. Our data revealed
      that the GO sheet size had a significant impact on different cellular parameters
      (i.e. cellular viability, ROS generation, and cellular activation). Indeed, the
      more the lateral dimensions of GO were reduced, the higher were the cellular
      internalization and the effects on cellular functionality. Our data also revealed
      a particular interaction of GO flakes with the cellular membrane. In fact, a GO
      mask due to the parallel arrangement of the graphene sheets on the cellular
      surface was observed. Considering the mask effect, we have hypothesized that this
      particular contact between GO sheets and the cell membrane could either promote
      their internalization or isolate cells from their environment, thus possibly
      accounting for the following impact on cellular parameters.

PMID- 24084793
TI  - A microfluidic device for immuno-affinity-based separation of mitochondria from
      cell culture.
AB  - In this work, we present a method to isolate mitochondria of mammalian cells
      after cell disruption on microscale. The device is composed of linear
      microchannels cast in PDMS (polydimethylsiloxane). Specific antibodies against
      the translocase outer membrane protein of the mitochondria are immobilized on the
      surface of the substrate using an avidin-biotin sandwich construct. The
      mitochondria can be captured in the channel, whereas the remains of the cell
      lysate flow out the chip unhindered. The captured mitochondria can be observed
      directly on chip. A successful immobilization of pre-isolated mitochondria was
      shown at a flow rate between 0 and 5 MUl min(-1) (~0-2.5 mm s(-1)). After
      fluorescence staining, we demonstrated that the mitochondria covered around 3% of
      the channel surface. The mitochondria appeared in a distinct spherical shape with
      a diameter of around 0.8-1.2 MUm. Further validation of the microfluidic device
      using non-treated cell lysate was done at 2 MUl min(-1). The immobilized
      mitochondria were smaller with a diameter of around ~490 nm. We observed a
      surface coverage of around 4%. The immobilized mitochondria were active and
      stable for over 2 h without cooling and were shown to be able to produce ATP
      under stage 3 respiration on chip. 

PMID- 24084795
TI  - The stereochemical course of tricho-acorenol biosynthesis.
AB  - The biosynthesis of tricho-acorenol in Trichoderma harzianum was investigated by
      feeding stereospecifically deuterated mevalonolactone isotopomers, followed by a
      detailed GC/MS analysis of the incorporation of labelling. The results establish
      a highly stereospecific hydride migration and antarafacial attack of water in the
      terminal step towards tricho-acorenol. 

PMID- 24084796
TI  - A turning point for scholarly osteopathic publications.

PMID- 24084797
TI  - The somatic connection: manual therapy is beneficial for cervical radiculopathy.

PMID- 24084798
TI  - Osteopathic training for MDs.

PMID- 24084800
TI  - Prevention of progressive back-specific dysfunction during pregnancy: an
      assessment of osteopathic manual treatment based on Cochrane Back Review Group
      criteria.
AB  - CONTEXT: Back pain during pregnancy may be associated with deficits in physical
      functioning and disability. Research indicates that osteopathic manual treatment
      (OMT) slows the deterioration of back-specific functioning during pregnancy.
      OBJECTIVE: To measure the treatment effects of OMT in preventing progressive back
      specific dysfunction during the third trimester of pregnancy using criteria
      established by the Cochrane Back Review Group. DESIGN: A randomized sham
      controlled trial including 3 parallel treatment arms: usual obstetric care and
      OMT (UOBC+OMT), usual obstetric care and sham ultrasound therapy (UOBC+SUT), and
      usual obstetric care (UOBC). SETTING: The Osteopathic Research Center within the
      University of North Texas Health Science Center in Fort Worth. PARTICIPANTS: A
      total of 144 patients were randomly assigned and included in intention-to-treat
      analyses. MAIN OUTCOME MEASURES: Progressive back-specific dysfunction was
      defined as a 2-point or greater increase in the Roland-Morris Disability
      Questionnaire (RMDQ) score during the third trimester of pregnancy. Risk ratios
      (RRs) and 95% confidence intervals (CIs) were used to compare progressive back
      specific dysfunction in patients assigned to UOBC+OMT relative to patients
      assigned to UOBC+SUT or UOBC. Numbers needed to treat (NNTs) and 95% CIs were
      also used to assess UOBC+OMT vs each comparator. Subgroup analyses were performed
      using median splits of baseline scores on a numerical rating scale for back pain
      and the RMDQ. RESULTS: Overall, 68 patients (47%) experienced progressive back
      specific dysfunction during the third trimester of pregnancy. Patients who
      received UOBC+OMT were significantly less likely to experience progressive back
      specific dysfunction (RR, 0.6; 95% CI, 0.3-1.0; P=.046 vs UOBC+SUT; and RR, 0.4;
      95% CI, 0.2-0.7; P<.0001 vs UOBC). The effect sizes for UOBC+OMT vs UOBC+SUT and
      for UOBC+OMT vs UOBC were classified as medium and large, respectively. The
      corresponding NNTs for UOBC+OMT were 5.1 (95% CI, 2.7-282.2) vs UOBC+SUT; and 2.5
      (95% CI, 1.8-4.9) vs UOBC. There was no statistically significant interaction
      between subgroups in response to OMT. CONCLUSION: Osteopathic manual treatment
      has medium to large treatment effects in preventing progressive back-specific
      dysfunction during the third trimester of pregnancy. The findings are potentially
      important with respect to direct health care expenditures and indirect costs of
      work disability during pregnancy.

PMID- 24084801
TI  - Influence of manual therapy on functional mobility after joint injury in a rat
      model.
AB  - CONTEXT: Animal models can be used to investigate manual therapy mechanisms, but
      testing manipulation in animal models is problematic because animals cannot
      directly report their pain. OBJECTIVE: To develop a rat model of inflammatory
      joint injury to test the efficacy of manual therapy in reducing nociception and
      restoring function. METHODS: The authors induced acute inflammatory joint injury
      in rats by injecting carrageenan into the ankle and then measured voluntary
      running wheel activity in treated and untreated rats. Treatments included manual
      therapy applied to the ankle and knee of the injured limb and several analgesic
      medications (eg, morphine, ketorolac, prednisone). RESULTS: Intra-articular
      injection of carrageenan to the ankle produced significant swelling (diameter of
      the ankle increased by 64% after injection; P=.004) and a robust reduction in
      voluntary running wheel activity (running distance reduced by 91% compared with
      controls; P<.001). Injured rats gradually returned to running levels equal to
      controls over 10 days. Neither manual therapy nor analgesic medications increased
      running wheel activity relative to untreated rats. CONCLUSION: Voluntary running
      wheel activity appears to be an appropriate functional measure to evaluate the
      impact of an acute inflammatory joint injury. However, efforts to treat the
      injury did not restore running relative to untreated rats.

PMID- 24084802
TI  - Retrospective medical record review of an osteopathic manipulative medicine
      hospital consultation service.
AB  - CONTEXT: In the first half of the 20th century, nearly all osteopathic physicians
      used osteopathic manipulative medicine (OMM) in the care of hospitalized
      patients. Over the past few decades, however, inpatient OMM care has declined and
      is more commonly provided by OMM specialists. OBJECTIVE: To retrospectively
      evaluate the details of a specialty-level OMM inpatient consultation service.
      METHODS: Inpatient OMM consultations that took place at Northeast Regional
      Medical Center in Kirksville, Missouri, between July 1998 and March 2008 were
      identified from billing records. Consultations were reviewed for demographic
      information, admission location, postoperative status, intensive care unit and
      mechanical ventilation usage, admission and discharge diagnoses, consultation
      reasons and final diagnoses, areas of somatic dysfunction treated and types of
      osteopathic manipulative treatment (OMT) techniques used, and hospital length of
      stay (LOS). RESULTS: A total of 1509 OMM consultations were identified (580 for
      male patients [38%]; 929 for female patients [62%]; mean [SD] age, 54 [31] years
      [range, 0-99 years]), representing 11% of all inpatient consultations. Of these,
      1372 consultations (91%) were initiated in the inpatient acute care facility, 87
      (6%) in the inpatient acute rehabilitation facility, and 50 (3%) in the skilled
      nursing facility. Further, 265 consultations (18%) were for postoperative
      patients, 187 (12%) were for patients in the intensive care unit, and 54 (4%)
      were for patients receiving mechanical ventilation at the time of the
      consultation. The most common admission diagnoses were hypertension, routine
      newborn care, lower respiratory infection, chronic obstructive pulmonary disease,
      and gastrointestinal symptoms. The most common reasons for OMM consultation were
      chest/rib pain, spinal pain, lower respiratory infection (adjunctive treatment),
      cranial asymmetry, and infant feeding disorder. The most common types of OMT
      techniques used were myofascial release, balanced ligamentous tension, muscle
      energy, soft tissue, and inhibition. The mean (SD) LOS was 5.7 (3.3) days (range,
      0-48 days), while the mean (SD) number of days the patient received OMT was 3.1
      (2.2) days. CONCLUSION: Medical records reviewed in the current study revealed
      that OMM consultations were ordered primarily for musculoskeletal complaints,
      respiratory problems (adjunctive treatment), and newborn care. A variety of OMT
      techniques were used. Further retrospective study is warranted to determine if
      OMM had an effect on LOS.

PMID- 24084803
TI  - Dementia: an evidence-based review of common presentations and family-based
      interventions.
AB  - The number of US older adults with dementia is expected to grow over the next
      several decades. For instance, the number of persons with Alzheimer disease is
      predicted to increase by 50% by 2030. Physicians commonly come into contact with
      patients who have dementia and, as such, need to understand its varied
      presentation. In the current review, the most common types of dementia, including
      Alzheimer disease, frontotemporal dementia, dementia due to vascular disease, and
      several others, are described. Characteristics and etiologic findings of cortical
      and subcortical dementias are differentiated, and cognitive profiles and symptoms
      of specific types of dementia are reviewed. An osteopathic approach to care,
      focusing on establishing a relationship with patients and their families, is also
      discussed. 

PMID- 24084804
TI  - Medicare reform and primary care concerns for future physicians.
AB  - The widening income gap between specialists and primary care physicians (PCPs)
      has spurred many physician associations to reform the current Resource-Based
      Relative Value Scale fee schedule and sustainable growth rate expenditure target
      system. Hoping to better represent primary care, the American Association of
      Family Physicians formed a task force in 2011 to suggest supplements to the
      Relative Value Update Committee's procedural code recommendations to the Centers
      for Medicare and Medicaid Services. In addition, the predicted shortage of PCPs
      has caused many medical schools to increase class sizes; the scarcity of PCPs has
      also spurred the founding of new medical schools. Such measures, however, have
      not been met with more residency program sites or graduate medical education
      funding. The present article highlights major Medicare reform strategies and
      explores several issues affecting the field of primary care, including
      reimbursement, representation, and residency training. 

PMID- 24084805
TI  - I can't move my face! a case of bilateral facial palsy.
AB  - The authors present a case of bilateral facial palsy in a 52-year-old man. The
      patient presented to an emergency department in Pennsylvania, describing left
      sided neck pain and headache from "sleeping wrong," symptoms which eventually
      progressed to facial diplegia by his fourth visit in 2 weeks. His admitting
      diagnosis was Bell palsy; he was ultimately tested for and found to have Lyme
      disease. Delay in treatment of patients with Lyme disease may lead to bilateral
      facial paralysis and disease progression. Thorough history taking, physical
      examination, and scrutiny of prior records are important elements of identifying
      and treating patients such as these (ie, whose vague symptoms progress to facial
      diplegia) appropriately. 

PMID- 24084806
TI  - Groin pain resulting from spondylodiscitis.

PMID- 24084807
TI  - Human disease locus discovery and mapping to molecular pathways through
      phylogenetic profiling.
AB  - Genes with common profiles of the presence and absence in disparate genomes tend
      to function in the same pathway. By mapping all human genes into about 1000
      clusters of genes with similar patterns of conservation across eukaryotic
      phylogeny, we determined that sets of genes associated with particular diseases
      have similar phylogenetic profiles. By focusing on those human phylogenetic gene
      clusters that significantly overlap some of the thousands of human gene sets
      defined by their coexpression or annotation to pathways or other molecular
      attributes, we reveal the evolutionary map that connects molecular pathways and
      human diseases. The other genes in the phylogenetic clusters enriched for
      particular known disease genes or molecular pathways identify candidate genes for
      roles in those same disorders and pathways. Focusing on proteins coevolved with
      the microphthalmia-associated transcription factor (MITF), we identified the
      Notch pathway suppressor of hairless (RBP-Jk/SuH) transcription factor, and
      showed that RBP-Jk functions as an MITF cofactor. 

PMID- 24084808
TI  - Genome-scale models of metabolism and gene expression extend and refine growth
      phenotype prediction.
AB  - Growth is a fundamental process of life. Growth requirements are well
      characterized experimentally for many microbes; however, we lack a unified model
      for cellular growth. Such a model must be predictive of events at the molecular
      scale and capable of explaining the high-level behavior of the cell as a whole.
      Here, we construct an ME-Model for Escherichia coli--a genome-scale model that
      seamlessly integrates metabolic and gene product expression pathways. The model
      computes ~80% of the functional proteome (by mass), which is used by the cell to
      support growth under a given condition. Metabolism and gene expression are
      interdependent processes that affect and constrain each other. We formalize these
      constraints and apply the principle of growth optimization to enable the accurate
      prediction of multi-scale phenotypes, ranging from coarse-grained (growth rate,
      nutrient uptake, by-product secretion) to fine-grained (metabolic fluxes, gene
      expression levels). Our results unify many existing principles developed to
      describe bacterial growth.

PMID- 24084809
TI  - Brain, reward, and eating disorders: a matter of taste?

PMID- 24084810
TI  - Social synchrony and oxytocin: from behavior to genes to therapeutics.

PMID- 24084811
TI  - The association between maternal smoking during pregnancy and bipolar disorder in
      the offspring: alternative interpretations.

PMID- 24084812
TI  - Severe irritability in youths: disruptive mood dysregulation disorder and
      associated brain circuit changes.

PMID- 24084813
TI  - The next 50 years: a new vision of "Community of Mental Health".

PMID- 24084814
TI  - DSM-5 sleep-wake disorders classification: overview for use in clinical practice.
AB  - Mental health clinicians should appreciate that sleep is a fundamental human
      behavior and that inadequate sleep has adverse medical, psychiatric, and
      psychosocial consequences. Sleep disturbances interact with common mental
      disorders; the two are mutually exacerbating, and both must be appropriately
      addressed to ensure optimal outcomes for our patients. Sleep is by the brain, of
      the brain, and for the brain.

PMID- 24084815
TI  - A fulfilling year of APA presidency: From DSM-5 to positive psychiatry.

PMID- 24084816
TI  - Response to the presidential address.

PMID- 24084817
TI  - Dilip V. Jeste, M.D., 139th President, 2012-2013.

PMID- 24084818
TI  - Infanticide in a case of folie a deux.

PMID- 24084820
TI  - Maternal smoking during pregnancy and bipolar disorder in offspring.
AB  - OBJECTIVE: Maternal smoking during pregnancy is associated with a number of
      adverse externalizing outcomes for offspring from childhood to adulthood. The
      relationship between maternal smoking and bipolar disorder in offspring, which
      includes externalizing symptoms among its many manifestations, has not been
      investigated in depth. The authors examined whether offspring exposed to maternal
      smoking in utero would be at increased lifetime risk for bipolar disorder after
      accounting for other factors related to maternal smoking. METHOD: Individuals
      with bipolar disorder (N=79) were ascertained from the birth cohort of the Child
      Health and Development Study. Case subjects were identified by a combination of
      clinical, database, and direct mailing sources; all case subjects were directly
      interviewed and diagnosed using DSM-IV criteria. Comparison subjects (N=654) were
      matched to case subjects on date of birth (+/-30 days), sex, membership in the
      cohort at the time of illness onset, and availability of maternal archived sera.
      RESULTS: After adjusting for potential confounders, offspring exposed to in utero
      maternal smoking exhibited a twofold greater risk for bipolar disorder (odds
      ratio=2.014, 95% confidence interval=1.48-2.53, p=0.01). The associations were
      noted primarily among bipolar offspring without psychotic features. CONCLUSIONS:
      Prenatal tobacco exposure may be one suspected cause of bipolar disorder.
      However, it will be necessary to account for other unmeasured familial factors
      before causal teratogenic effects can be suggested.

PMID- 24084821
TI  - Elevated CSF Tau is associated with psychosis in Alzheimer's disease.

PMID- 24084822
TI  - Chronic benign neutropenia/agranulocytosis associated with non-clozapine
      antipsychotics.

PMID- 24084829
TI  - Self-assembly of water-soluble TPPS in organic solvents: from nanofibers to
      mirror imaged chiral nanorods.
AB  - Water-soluble TPPS was found to self-assemble into long nanofibers of ambiguous
      chirality in organic solvents, while mirror imaged chiroptical nanorods with
      controlled chirality were formed when (1R,2R)-(-)- or (1S,2S)-(+)-1,2
      diaminocyclohexane was involved during the self-assembly. 

PMID- 24084832
TI  - Human hair follicle stem cell differentiation into contractile smooth muscle
      cells is induced by transforming growth factor-beta1 and platelet-derived growth
      factor BB.
AB  - Smooth muscle cells (SMCs) are important in vascular homeostasis and disease and
      thus, are critical elements in vascular tissue engineering. Although adult SMCs
      have been used as seed cells, such mature differentiated cells suffer from
      limited proliferation potential and cultural senescence, particularly when
      originating from older donors. By comparison, human hair follicle stem cells
      (hHFSCs) are a reliable source of stem cells with multi-differentiation
      potential. The aim of the present study, was to develop an efficient strategy to
      derive functional SMCs from hHFSCs. hHFSCs were obtained from scalp tissues of
      healthy adult patients undergoing cosmetic plastic surgery. The hHFSCs were
      expanded to passage 2 and induced by the administration of transforming growth
      factor-beta1 (TGF-beta1) and platelet-derived growth factor BB (PDGF-BB) in
      combination with culture medium. Expression levels of SMC-related markers,
      including alpha-smooth muscle actin (alpha-SMA), alpha-calponin and smooth muscle
      myosin heavy chain (SM-MHC), were detected by immunofluorescence staining, flow
      cytometry analysis and reverse transcription-polymerase chain reaction (RT-PCR).
      When exposed to differentiation medium, hHFSCs expressed early, mid and late
      markers (alpha-SMA, alpha-calponin and SM-MHC, respectively) that were similar to
      the markers expressed by human umbilical artery SMCs. Notably, when entrapped
      inside a collagen matrix lattice, these SM differentiated cells showed a
      contractile function. Therefore, the present study developed an efficient
      strategy for differentiating hHFSCs into contractile SMCs by stimulation with TGF
      beta1 and PDGF-BB. The high yield of derivation suggests that this strategy
      facilitates the acquisition of the large numbers of cells that are required for
      blood vessel engineering and the study of vascular disease pathophysiology.

PMID- 24084833
TI  - Fabrication of hollow metal oxide nanocrystals by etching cuprous oxide with
      metal(II) ions: approach to the essential driving force.
AB  - Hollow metal oxide nanocrystals were prepared by etching cuprous oxide with metal
      ions and were applied as photoelectrodes. As a hard template,
      polyvinylpyrrolidone stabilized cuprous oxide (PVP-Cu2O) and non-stabilized
      cuprous oxide (nPVP-Cu2O) were synthesized by a precipitation method. Hollow iron
      oxide and cobalt oxide nanocrystals with a truncated octahedral morphology were
      fabricated by an etching reaction with transition metal(II) ions (Fe(2+) or
      Co(2+)). In the etching reaction process, a cationic exchange reaction occurs
      between the divalent metal ion and Cu(+) due to the higher Lewis acidity. Facet
      selective etching of cuprous oxide has been observed during the ionic exchange
      reaction of Cu(+) and O(2-) ions in PVP-Cu2O complexes with transition metal(II)
      ions (Fe(2+) or Co(2+)) at the surface of a (110) facet. Amorphous states of
      hollow metal oxide products were annealed to form alpha-Fe2O3 (hematite) and
      Co3O4 and their crystal structure was examined with X-ray diffraction and HR-TEM.
      The optical absorption behavior of semiconductor nanocrystals was measured with
      UV-vis spectroscopy to define band gap energy. The hollow hematite structure has
      a 2.08 eV band gap and Co3O4 (Co(II,III) oxide) has a 1.80 eV indirect band gap.
      Using these hollow nanocrystals, a metal oxide monolayer film was fabricated with
      a secondary growth approach and was studied for its photocatalytic properties.

PMID- 24084831
TI  - Reduced anterior temporal and hippocampal functional connectivity during face
      processing discriminates individuals with social anxiety disorder from healthy
      controls and panic disorder, and increases following treatment.
AB  - Group functional magnetic resonance imaging (fMRI) studies suggest that anxiety
      disorders are associated with anomalous brain activation and functional
      connectivity (FC). However, brain-based features sensitive enough to discriminate
      individual subjects with a specific anxiety disorder and that track symptom
      severity longitudinally, desirable qualities for putative disorder-specific
      biomarkers, remain to be identified. Blood oxygen level-dependent (BOLD) fMRI
      during emotional face perceptual tasks and a new, large-scale and condition
      dependent FC and machine learning approach were used to identify features (pair
      wise correlations) that discriminated patients with social anxiety disorder (SAD,
      N=16) from controls (N=19). We assessed whether these features discriminated SAD
      from panic disorder (PD, N=16), and SAD from controls in an independent
      replication sample that performed a similar task at baseline (N: SAD=15,
      controls=17) and following 8-weeks paroxetine treatment (N: SAD=12, untreated
      controls=7). High SAD vs HCs discrimination (area under the ROC curve, AUC,
      arithmetic mean of sensitivity and specificity) was achieved with two FC features
      during unattended neutral face perception (AUC=0.88, P<0.05 corrected). These
      features also discriminated SAD vs PD (AUC=0.82, P=0.0001) and SAD vs HCs in the
      independent replication sample (FC during unattended angry face perception,
      AUC=0.71, P=0.01). The most informative FC was left hippocampus-left temporal
      pole, which was reduced in both SAD samples (replication sample P=0.027), and
      this FC increased following the treatment (post>pre, t(11)=2.9, P=0.007). In
      conclusion, SAD is associated with reduced FC between left temporal pole and left
      hippocampus during face perception, and results suggest promise for emerging FC
      based biomarkers for SAD diagnosis and treatment effects. 

PMID- 24084834
TI  - ChemR23 knockout mice display mild obesity but no deficit in adipocyte
      differentiation.
AB  - Chemerin was initially described as a chemoattractant factor for leukocyte
      populations. More recently, the protein has also been reported to be an
      adipokine, regulating adipocyte differentiation in vitro via its receptor
      ChemR23, and to be correlated with BMI and other parameters of the metabolic
      syndrome in humans. The aim of this study was to investigate the role of the
      chemerin/ChemR23 axis in the regulation of metabolism in vivo, using a mouse
      knockout (KO) model for ChemR23 (Cmklr1) in a C57BL/6 genetic background. Body
      weight and adipose tissue mass did not differ significantly in young animals, but
      were significantly higher in ChemR23 KO mice aged above 12 months. Glucose
      tolerance was unaffected. No significant modifications in the levels of blood
      lipids were observed and no increase in the levels of inflammatory markers was
      observed in the adipose tissue of KO mice. A high-fat diet did not exacerbate the
      obese phenotype in ChemR23 KO mice. No obvious defect in adipocyte
      differentiation was detected, while a marker of lipogenic activity (GPD1
      expression) was found to be elevated. In conclusion, the chemerin/ChemR23 system
      does not appear to play a major role in adipocyte differentiation in vivo, but it
      may be involved in adipose tissue homeostasis. 

PMID- 24084835
TI  - Developmental androgen excess disrupts reproduction and energy homeostasis in
      adult male mice.
AB  - Polycystic ovary syndrome is a common endocrine disorder in females of
      reproductive age and is believed to have a developmental origin in which
      gestational androgenization programs reproductive and metabolic abnormalities in
      offspring. During gestation, both male and female fetuses are exposed to
      potential androgen excess. In this study, we determined the consequences of
      developmental androgenization in male mice exposed to neonatal testosterone
      (NTM). Adult NTM displayed hypogonadotropic hypogonadism with decreased serum
      testosterone and gonadotropin concentrations. Hypothalamic KiSS1 neurons are
      believed to be critical to the onset of puberty and are the target of leptin.
      Adult NTM exhibited lower hypothalamic Kiss1 expression and a failure of leptin
      to upregulate Kiss1 expression. NTM displayed an early reduction in lean mass,
      decreased locomotor activity, and decreased energy expenditure. They displayed a
      delayed increase in subcutaneous white adipose tissue amounts. Thus, excessive
      neonatal androgenization disrupts reproduction and energy homeostasis and
      predisposes to hypogonadism and obesity in adult male mice. 

PMID- 24084836
TI  - Manipulating complex light with metamaterials.
AB  - Recent developments in the field of metamaterials have revealed unparalleled
      opportunities for "engineering" space for light propagation; opening a new
      paradigm in spin- and quantum-related phenomena in optical physics. Here we show
      that unique optical properties of metamaterials (MMs) open unlimited prospects to
      "engineer" light itself. We propose and demonstrate for the first time a novel
      way of complex light manipulation in few-mode optical fibers using optical MMs.
      Most importantly, these studies highlight how unique properties of MMs, namely
      the ability to manipulate both electric and magnetic field components of
      electromagnetic (EM) waves, open new degrees of freedom in engineering complex
      polarization states of light at will, while preserving its orbital angular
      momentum (OAM) state. These results lay the first steps in manipulating complex
      light in optical fibers, likely providing new opportunities for high capacity
      communication systems, quantum information, and on-chip signal processing. 

PMID- 24084837
TI  - Longitudinal analysis of peritoneal fluid transport and its determinants in a
      cohort of incident peritoneal dialysis patients.
AB  - BACKGROUND AND OBJECTIVES: There is a paucity of large longitudinal studies on
      the time course of peritoneal fluid transport. The aim of the present study was
      to longitudinally analyze changes in fluid transport and relevant solute
      transport parameters in patients treated with a conventional peritoneal dialysis
      (PD) fluid and, to mimic clinical reality, not selected for the presence or
      absence of ultrafiltration (UF) failure. METHODS: This prospective single-center
      cohort study followed 138 consecutive incident PD patients from July 1994 until
      censoring in August 2004. The design was longitudinal, with repeated measures
      over time in each patient. Patients had undergone at least 1 and a maximum of 5
      annual standard peritoneal permeability analyses (SPAs) using 3.86% glucose
      dialysate. A linear mixed model was used to analyze the longitudinal data.
      RESULTS: No differences in patient characteristics were present at baseline in
      relation to the number of available SPAs. There were also no differences in
      patient withdrawal during the years of follow-up. A gradual decline in fluid
      transport, expressed as free water transport (FWT), small-pore fluid transport
      (SPFT), and transcapillary UF (TCUF), was observed with duration of PD. The
      decline was mainly attributable to patients who developed UF failure. The time
      courses for the determinants of fluid transport, such as the reflection
      coefficient (sigma) and the UF coefficient (LpA), were not different. However,
      they were associated with an increase in the mass transfer area coefficient of
      creatinine, reflecting the peritoneal vascular surface area. CONCLUSIONS: Fluid
      profiles for FWT and SPFT during a dwell can be explained by current knowledge of
      the three-pore model. Fluid transport declines with the duration of PD because of
      an increase in the vascular surface area, leading to a rapid dissipation of
      glucose as the osmotic agent. The absence of a trend in the time course of
      osmotic conductance and its constituents-that is, LpA and sigma-suggests that, in
      an unselected population, these parameters are affected only late in the time
      course of PD.

PMID- 24084838
TI  - Increased risk of fatal infections in women starting peritoneal dialysis.
AB  - BACKGROUND AND OBJECTIVES: Although cardiovascular disease (CVD) is an important
      cause of morbidity and mortality in patients with end-stage renal disease, non
      CVD causes account for more than 50% of total deaths. We previously showed that,
      compared with men, women starting dialysis-- both hemodialysis and peritoneal
      dialysis (PD)--have higher non-CVD mortality rates. Here, we evaluate sex
      specific outcomes in a large cohort of incident PD patients. METHODS: Incident de
      novo PD patients from the Andalusian SICATA Registry for 1999 - 2010, with follow
      up until 31 December 2010 or up to 5 years, were investigated for fatal outcomes.
      Causes of death were extracted from medical records. The analysis used
      traditional and competing-risk Cox models for all-cause and cause-specific
      mortality in men and women, correcting in the competing-risk models for the
      events of kidney transplantation and transfer to hemodialysis. RESULTS: A total
      of 1458 patients (57% men; mean overall age: 55.3 +/- 17.0 years) initiated PD in
      Andalusia during the study period. During follow-up, 350 deaths, 355 renal
      transplantation procedures, and 331 transfers to hemodialysis were recorded.
      Vascular disease and diabetic nephropathy were the most frequent causes of kidney
      failure in men; other causes were more common in women. In the traditional Cox
      model, both sexes showed a similar all-cause mortality risk [crude hazard ratio
      (HR): 0.90; 95% confidence interval (CI): 0.72 to 1.12]. However, with respect to
      specific causes of death, women showed a borderline lower risk of both CVD (crude
      HR: 0.71; 95% CI: 0.50 to 0.99) and non-CVD mortality from other than infection
      (crude HR: 0.81; 95% CI: 0.57 to 1.15). In contrast, the risk of death from
      infection was almost doubled in women compared with men (crude HR: 1.92; 95% CI:
      1.15 to 3.20), a finding that held true after multivariate adjustment for age,
      primary renal disease, period of inclusion, and initial PD modality (adjusted HR:
      1.76; 95% CI: 1.03 to 3.01). This result was confirmed even taking into
      consideration the competing events of kidney transplantation and transfer to
      hemodialysis. CONCLUSIONS: Compared with men starting PD, women starting PD are
      at higher risk of mortality from infection. More stringent screening measures and
      corrective efforts in women might be indicated.

PMID- 24084839
TI  - A new simplified one-port laparoscopic technique for peritoneal dialysis catheter
      placement.
AB  - BACKGROUND: Various techniques for laparoscopic insertion of a peritoneal
      dialysis catheter have been described. Usually 2 - 3 ports are required, and
      complications related to the port sites (such as abdominal wall hernia, leakage,
      and hemorrhage) cannot be avoided. To minimize the potential complications, we
      designed a simplified 1-port laparoscopic technique for peritoneal dialysis
      catheter placement. ? METHODS: We conducted a retrospective data review of 44
      patients who underwent 1-port laparoscopic insertion of a Tenckhoff catheter from
      June 2009 to February 2011. All patient data, including postoperative
      complications, were analyzed. ? RESULTS: The mean follow-up period was 11.52
      months. All catheters were working properly, except in 1 patient who developed
      peritonitis 3 months after catheter placement. (The catheter was removed.) No
      postoperative abdominal wall hemorrhage, early leaks, hernias, or catheter
      migration occurred. No exit-site or tunnel infections were observed. ?
      CONCLUSIONS: Our 1-port laparoscopic technique provides excellent catheter
      fixation, avoids excessive port sites, and yields good cosmesis. The low
      complication rate and the simplicity of the method justify its standard use for
      Tenckhoff catheter placement.

PMID- 24084840
TI  - Predictors of peritonitis and the impact of peritonitis on clinical outcomes of
      continuous ambulatory peritoneal dialysis patients in Taiwan--10 years'
      experience in a single center.
AB  - OBJECTIVE: Peritoneal dialysis (PD) has become more prevalent as a treatment
      modality for end-stage renal disease, and peritonitis remains one of its most
      devastating complications. The aim of the present investigation was to examine
      the frequency and predictors of peritonitis and the impact of peritonitis on
      clinical outcomes. ? METHODS: Our retrospective observational cohort study
      enrolled 391 patients who had been treated with continuous ambulatory PD (CAPD)
      for at least 90 days. Relevant demographic, biochemical, and clinical data were
      collected for an analysis of CAPD-associated peritonitis, technique failure, drop
      out from PD, and patient mortality. ? RESULTS: The peritonitis rate was 0.196
      episodes per patient-year. Older age (>65 years) was the only identified risk
      factor associated with peritonitis. A multivariate Cox regression model
      demonstrated that technique failure occurred more often in patients experiencing
      peritonitis than in those free of peritonitis (p < 0.001). Kaplan-Meier analysis
      revealed that the group experiencing peritonitis tended to survive longer than
      the group that was peritonitis-free (p = 0.11). After multivariate adjustment,
      the survival advantage reached significance (hazard ratio: 0.64; 95% confidence
      interval: 0.46 to 0.89; p = 0.006). Compared with the peritonitis-free group, the
      group experiencing peritonitis also had more drop-out from PD (p = 0.03). ?
      CONCLUSIONS: The peritonitis rate was relatively low in the present
      investigation. Elderly patients were at higher risk of peritonitis episodes.
      Peritonitis independently predicted technique failure, in agreement with other
      reports. However, contrary to previous studies, all-cause mortality was better in
      patients experiencing peritonitis than in those free of peritonitis. The
      underlying mechanisms of this presumptive "peritonitis paradox" remain to be
      clarified.

PMID- 24084841
TI  - Predictors of peritonitis, hospital days, and technique survival for peritoneal
      dialysis patients in a managed care setting.
AB  - INTRODUCTION: Many clinicians perceive that peritoneal dialysis (PD) should be
      reserved for younger, healthier, more affluent patients. Our aim was to examine
      outcomes for PD patients in a managed care setting and to identify predictors of
      adverse outcomes. METHODS: We identified all patients who initiated PD at our
      institution between 1 January 2001 and 31 December 2010. Predictor variables
      studied included age, sex, race, PD modality, cause of end-stage renal disease
      (ESRD), dialysis vintage, Charlson comorbidity index (CCI) score, education, and
      income level. Poisson models were used to determine the relative risk (RR) of
      peritonitis and the number of hospital days per patient-year. The log-rank test
      was used to compare technique survival by patient strata. RESULTS: Among the 1378
      patients who met the inclusion criteria, only female sex [RR: 0.85; 95%
      confidence interval (CI): 0.74 to 0.98; p = 0.02] and higher education (RR: 0.77;
      95% CI: 0.60 to 0.98; p = 0.04) were associated with peritonitis. For hospital
      days, dialysis vintage (RR: 1.11; 95% CI: 1.04 to 1.18; p = 0.002), CCI score
      (RR: 1.06; 95% CI: 1.02 to 1.20; p = 0.002), and cause of ESRD (RR for
      glomerulonephritis: 0.59; 95% CI: 0.43 to 0.80; p = 0.0006; and RR for
      hypertension: 0.69; 95% CI: 0.55 to 0.88; p = 0.002) were associated with 1 extra
      hospital day per patient-year. The 2-year technique survival was 61% for patients
      who experienced at least 1 episode of peritonitis and 72% for those experiencing
      no peritonitis (p = 0.0001). Baseline patient age, primary cause of ESRD, and PD
      modality were the only other variables associated with technique survival in the
      study. CONCLUSIONS: Neither race nor socio-economic status predicted technique
      survival or hospital days in our study. Female sex and higher education were the
      only two variables studied that had an association with peritonitis.

PMID- 24084842
TI  - Percutaneous peritoneal dialysis catheter insertion by a nephrologist: a new,
      simple, and safe technique.
AB  - BACKGROUND: Insertion of the peritoneal dialysis (PD) catheter by a nephrologist
      has been encouraged by several studies. The ultimate goal is to provide safe,
      timely, and effective catheter insertion without an unduly long wait time or
      delay. The success of PD depends partly on the ease of catheter insertion. We
      developed a new technique for percutaneous PD catheter insertion by
      nephrologists. Our new technique, in addition to being easy, proved to be safe
      and to eliminate the need for the peel-away sheath. METHODS: Data were collected
      prospectively on all patients having a PD catheter inserted by a nephrologist
      using our new technique (40 catheters in 38 patients). All catheters were
      evaluated for infectious and mechanical complications. RESULTS: The mean duration
      of the procedure from skin sterilization to the end of insertion was 24 +/- 3
      minutes. No bowel perforation or serious hemorrhage was recorded. Poor initial
      drainage was recorded in 12.5% of the catheters (n = 5) during the 4 weeks after
      insertion. The incidence of early exit-site leakage was 2.5% (1 catheter).
      Episodes of exit-site infection occurred in 5.0% and 12.5% of catheters (within 1
      month and by the end of study period respectively). Two episodes of peritonitis
      were reported by the end of the 12-month period. Catheter survival was 95.0% and
      87.5% at 6 months and 12 months respectively. CONCLUSIONS: Percutaneous bedside
      placement of PD catheters using our new technique is safe and carries less
      morbidity in terms of bowel perforation, catheter-related infection, and exit
      site leak. In addition, our new technique appears to have a high success rate and
      to offer considerable savings in terms of operating time.

PMID- 24084844
TI  - Theoretical study on the mechanism and stereochemistry of the cinchona-thiourea
      organocatalytic hydrophosphonylation of an alpha-ketoester.
AB  - The mechanism and stereochemistry of the hydrophosphonylation of an alpha
      ketoester with dimethylphosphonate (DMHP) catalyzed by a thiourea-cinchona
      organocatalyst have been studied by the ONIOM method. The calculations show that
      the catalytic cycle is a three-step process, including the deprotonation of DMHP,
      C-P bond formation via nucleophilic addition and proton transfer with the
      regeneration of the catalyst. The deprotonation of DMHP mediated by the basicity
      of the quinuclidine nitrogen atom is the rate-determining step for the entire
      reaction. The activation of the alpha-ketoester by the thiourea or protonated
      cinchona moiety of the bifunctional catalyst is comparatively investigated, and
      the former is energy-preferred. AIM combined with NBO analysis indicate that the
      multiple hydrogen bonds play essential roles in activating substrates,
      facilitating charge transfer and stabilizing transition states and intermediates.
      The stereochemistry of the reaction is controlled by the C-P bond formation step
      and originated from the chiral induction of the multiple hydrogen-bonding
      interactions. The bulkier substituent groups on the chiral scaffold of the
      catalyst may increase rigidity of the catalyst and the asymmetric induction to
      the substrates. The calculations predict that alkyl substituted alpha-ketoesters
      might also be converted to chiral alpha-hydroxyl phosphonates with high
      enantioselectivity. 

PMID- 24084843
TI  - Is dialysis modality a factor in the survival of patients initiating dialysis
      after kidney transplant failure?
AB  - BACKGROUND: Kidney transplant failure (TF) is among the leading causes of
      dialysis initiation. Whether survival is similar for patients treated with
      peritoneal dialysis (PD) and with hemodialysis (HD) after TF is unclear and may
      inform decisions concerning dialysis modality selection. METHODS: Between 1995
      and 2007, 16 113 adult dialysis patients identified from the US Renal Data System
      initiated dialysis after TF. A multivariable Cox proportional hazards model was
      used to evaluate the impact of initial dialysis modality (1 865 PD, 14 248 HD) on
      early (1-year) and overall mortality in an intention-to-treat approach. RESULTS:
      Compared with HD patients, PD patients were younger (46.1 years vs 49.4 years, p
      < 0.0001) with fewer comorbidities such as diabetes mellitus (23.1% vs 25.7%, p <
      0.0001). After adjustment, survival among PD patients was greater within the
      first year after dialysis initiation [adjusted hazard ratio (AHR): 0.85; 95%
      confidence interval (CI): 0.74 to 0.97], but lower after 2 years (AHR: 1.15; 95%
      CI: 1.02 to 1.29). During the entire period of observation, survival in both
      groups was similar (AHR for PD compared with HD: 1.09; 95% CI: 1.0 to 1.20). In a
      sensitivity analysis restricted to a cohort of 1865 propensity-matched pairs of
      HD and PD patients, results were similar (AHR: 1.03; 95% CI: 0.93 to 1.14).
      Subgroups of patients with a body mass index exceeding 30 kg/m(2) [AHR: 1.26; 95%
      CI: 1.05 to 1.52) and with a baseline estimated glomerular filtration rate (eGFR)
      less than 5 mL/min/1.73 m(2) (AHR: 1.45; 95% CI: 1.05 to 1.98) experienced
      inferior overall survival when treated with PD. CONCLUSIONS: Compared with HD, PD
      is associated with an early survival advantage, inferior late survival, and
      similar overall survival in patients initiating dialysis after TF. Those data
      suggest that increased initial use of PD among patients returning to dialysis
      after TF may be associated with improved outcomes, except among patients with a
      higher BMI and those who initiate dialysis at lower levels of eGFR. The reasons
      behind the inferior late survival seen in PD patients are unclear and require
      further study.

PMID- 24084846
TI  - Delivery of Functional Anti-miR-9 by Mesenchymal Stem Cell-derived Exosomes to
      Glioblastoma Multiforme Cells Conferred Chemosensitivity.
AB  - Glioblastoma multiforme (GBM), the most common and lethal tumor of the adult
      brain, generally shows chemo- and radioresistance. MicroRNAs (miRs) regulate
      physiological processes, such as resistance of GBM cells to temozolomide (TMZ).
      Although miRs are attractive targets for cancer therapeutics, the effectiveness
      of this approach requires targeted delivery. Mesenchymal stem cells (MSCs) can
      migrate to the sites of cancers, including GBM. We report on an increase in miR-9
      in TMZ-resistant GBM cells. miR-9 was involved in the expression of the drug
      efflux transporter, P-glycoprotein. To block miR-9, methods were developed with
      Cy5-tagged anti-miR-9. Dye-transfer studies indicated intracellular communication
      between GBM cells and MSCs. This occurred by gap junctional intercellular
      communication and the release of microvesicles. In both cases, anti-miR-9 was
      transferred from MSCs to GBM cells. However, the major form of transfer occurred
      with the microvesicles. The delivery of anti-miR-9 to the resistant GBM cells
      reversed the expression of the multidrug transporter and sensitized the GBM cells
      to TMZ, as shown by increased cell death and caspase activity. The data showed a
      potential role for MSCs in the functional delivery of synthetic anti-miR-9 to
      reverse the chemoresistance of GBM cells.Molecular Therapy-Nucleic Acids (2013)
      2, e126; doi:10.1038/mtna.2013.60; published online 1 October 2013. 

PMID- 24084845
TI  - Long-term Expression of Apolipoprotein B mRNA-specific Hammerhead Ribozyme via
      scAAV8.2 Vector Inhibits Atherosclerosis in Mice.
AB  - Target substrate-specific hammerhead ribozyme cleaves the specific mRNA
      efficiently and results in the inhibition of gene expression. In humans,
      overproduction of apolipoprotein B (apoB) is positively associated with premature
      coronary artery diseases. The goal of this study is to demonstrate that long-term
      reduction of apoB gene expression using hammerhead ribozyme would result in
      inhibition of atherosclerosis development. We designed two hammerhead ribozymes
      targeted at the nucleotides of apoB mRNA GUC(2326) (designated RB1) and GUA(6679)
      (designated RB15), and we used self-complementary adeno-associated virus 8.2
      (scAAV8.2) vector to deliver these active ribozymes of RB1, RB15, combination of
      RB1/RB15, and an inactive hammerhead ribozyme RB15 mutant to atherosclerosis
      prone LDb mice (Ldlr(-/-)Apobec1(-/-)). LDb mice lack both low density
      lipoproteins (LDL) receptor (Ldlr(-/-)) and apoB mRNA editing enzyme (Apobec1(-/
      )) genes and develop atherosclerosis spontaneously. After the RB1, RB15, or
      combination of RB1/RB15 ribozymes treatment, the LDb mice had significantly
      decreased plasma triglyceride and apoB levels, resulting in markedly decreased of
      atherosclerotic lesions, Furthermore, the active ribozymes treatment decreased
      the levels of diacylglycerol acyltransferase 1 (Dgat1) mRNA and the levels of
      multiple diacylglycerol (DAG) molecular species. These results provide the first
      evidence that decreased apoB levels results to reduction of Dgat1 expression and
      triglyceride levels (TAG), which had a significant impact on the development of
      atherosclerosis.Molecular Therapy-Nucleic Acids (2013) 2, e125;
      doi:10.1038/mtna.2013.53; published online 1 October 2013. 

PMID- 24084847
TI  - Influence of organic surface coatings on the sorption of anticonvulsants on
      mineral surfaces.
AB  - Here, we explore the role that sorption to mineral surfaces plays in the fate of
      two commonly encountered effluent-derived pharmaceuticals, the anticonvulsants
      phenytoin and carbamazepine. Adsorption isotherms and pH-edge experiments are
      consistent with electrostatics governing anticonvulsant uptake on metal oxides
      typically found in soil and aquifer material (e.g., Si, Al, Fe, Mn, and Ti).
      Appreciable, albeit limited, adsorption was observed only for phenytoin, which is
      anionic above pH 8.3, on the iron oxides hematite and ferrihydrite. Adsorption
      increased substantially in the presence of cationic and anionic surfactants,
      species also commonly encountered in wastewater effluent. For carbamazepine, we
      propose the enhanced uptake results entirely from hydrophobic interactions with
      apolar tails of surfactant surface coatings. For phenytoin, adsorption also
      arises from the ability of surfactants to alter the net charge of the mineral
      surface and thereby further enhance favorable electrostatic interactions with its
      anionic form. Collectively, our results demonstrate that although pristine
      mineral surfaces are likely not major sinks for phenytoin and carbamazepine in
      the environment, their alteration with organic matter, particularly surfactants,
      can considerably increase their ability to retain these emerging pollutants in
      subsurface systems. 

PMID- 24084848
TI  - A general protocol to afford enantioenriched linear homoprenylic amines.
AB  - The reaction of a readily obtained chiral branched homoprenylamonium salt with a
      range of aldehydes, including aliphatic substrates, affords the corresponding
      linear isomers in good yields and enantioselectivities. 

PMID- 24084850
TI  - Sample preparation for single molecule localization microscopy.
AB  - Single molecule localization-based optical nanoscopy was introduced in 2006,
      surpassing traditional diffraction-limited resolutions by an order of magnitude.
      Seven years later, this superresolution technique is continuing to follow a trend
      of increasing popularity and pervasiveness, with the proof-of-concept work long
      finished and commercial implementations now available. However one important
      aspect that tends to become lost in translation is the importance of proper
      sample preparation, with very few resources addressing the considerations that
      must be made when preparing samples for imaging with single molecule level
      sensitivity. Presented here is a an in-depth analysis of all aspects of sample
      preparation for single molecule superresolution, including both live and fixed
      cell preparation, choice of fluorophore, fixation and staining techniques, and
      imaging buffer considerations. 

PMID- 24084851
TI  - A ZnO nanowire-based photo-inverter with pulse-induced fast recovery.
AB  - We demonstrate a fast response photo-inverter comprised of one transparent gated
      ZnO nanowire field-effect transistor (FET) and one opaque FET respectively as the
      driver and load. Under ultraviolet (UV) light the transfer curve of the
      transparent gate FET shifts to the negative side and so does the voltage transfer
      curve (VTC) of the inverter. After termination of UV exposure the recovery of
      photo-induced current takes a long time in general. This persistent
      photoconductivity (PPC) is due to hole trapping on the surface of ZnO NWs. Here,
      we used a positive voltage short pulse after UV exposure, for the first time
      resolving the PPC issue in nanowire-based photo-detectors by accumulating
      electrons at the ZnO/dielectric interface. We found that a pulse duration as
      small as 200 ns was sufficient to reach a full recovery to the dark state from
      the UV induced state, realizing a fast UV detector with a voltage output. 

PMID- 24084849
TI  - Comprehensive identification of mutational cancer driver genes across 12 tumor
      types.
AB  - With the ability to fully sequence tumor genomes/exomes, the quest for cancer
      driver genes can now be undertaken in an unbiased manner. However, obtaining a
      complete catalog of cancer genes is difficult due to the heterogeneous molecular
      nature of the disease and the limitations of available computational methods.
      Here we show that the combination of complementary methods allows identifying a
      comprehensive and reliable list of cancer driver genes. We provide a list of 291
      high-confidence cancer driver genes acting on 3,205 tumors from 12 different
      cancer types. Among those genes, some have not been previously identified as
      cancer drivers and 16 have clear preference to sustain mutations in one specific
      tumor type. The novel driver candidates complement our current picture of the
      emergence of these diseases. In summary, the catalog of driver genes and the
      methodology presented here open new avenues to better understand the mechanisms
      of tumorigenesis. 

PMID- 24084852
TI  - [The relevance of biomarkers for personalised medicine].
AB  - In this paper the relevance of biomarkers for the benefit/risk assessment of
      pharmaceuticals and the validation of biomarkers within clinical trials is
      presented. For this purpose the most important study designs for validation are
      described and discussed. Using the example of the development of rosuvastatin and
      the validation of hs-CRP (JUPITER study), aspects that are necessary for the
      planning of a joint development program for a pharmaceutical drug and a biomarker
      are discussed. In addition, alternatives considering how the validation of the
      biomarker could be involved in the entire development program of the
      pharmaceutical drug are presented. 

PMID- 24084853
TI  - Stabilized gold nanorod-dye conjugates with controlled resonance coupling create
      bright surface-enhanced resonance Raman nanotags.
AB  - The preparation and characterization of stable and non-aggregated colloidal
      suspensions of gold nanorod-molecular dye complexes which exhibit very bright
      surface-enhanced resonance Raman scattering (SERRS) signals is described. A
      systematic study was performed where both the localized surface plasmon resonance
      (LSPR) of the nanorod and the molecular resonance of dyes adsorbed onto the rod
      surface were selectively tuned with respect to the laser excitation wavelengths.
      Resonance coupling was found to be a significant factor in the overall SERRS
      enhancement. The polymer stabilized nanorod-dye conjugates were prepared without
      the added complexity of nanoparticle aggregation as well as having good control
      over the surface coverage and orientation of the dye molecules. Furthermore, we
      demonstrate that this new class of Raman nanotags greatly outperforms an approach
      based on quasi-spherical gold nanoparticles. 

PMID- 24084854
TI  - Induction of autophagy contributes to the myocardial protection of valsartan
      against ischemia-reperfusion injury.
AB  - The mechanisms underlying the myocardial protection of valsartan against
      ischemia/reperfusion (I/R) injury are complicated and remain unclear. The aim of
      this study was to investigate whether autophagy machinery was involved in the
      protection against I/R injury that is induced by valsartan. In vivo rat hearts
      were subjected to ischemia by 30 min ligation of the left anterior descending
      coronary artery, followed by a 120 min reperfusion. 3-methyladenine (3-MA), a
      specific inhibitor on autophagic sequestration, was used to inhibit autophagy.
      The hemodynamics, infarct size of the ventricle and LC3B protein were measured.
      Western blot analysis was performed to investigate the mechanism by which
      autophagy was induced by valsartan. Valsartan preconditioning resulted in a
      significant decrease in infarct size and induced autophagy in the rat heart
      subjected to I/R injury. The hemodynamics assay showed that the valsartan-induced
      cardiac functional recovery was attenuated by 3-MA. By contrast, 3-MA decreased
      the improvement induced by valsartan on the histology and infarction of the rat
      heart subjected to I/R injury. Valsartan preconditioning induced autophagy via
      the AKT/mTOR/S6K pathway, independent of Beclin1. In conclusion, valsartan
      preconditioning induced autophagy via the AKT/mTOR/S6K pathway, which contributed
      to the myocardial protection against I/R injury.

PMID- 24084855
TI  - Detection of cerebral ischemia using the power spectrum of the pulse wave
      measured by near-infrared spectroscopy.
AB  - The diagnosis and medical treatment of cerebral ischemia are becoming more
      important due to the increase in the prevalence of cerebrovascular disease.
      However, conventional methods of evaluating cerebral perfusion have several
      drawbacks: they are invasive, require physical restraint, and the equipment is
      not portable, which makes repeated measurements at the bedside difficult. An
      alternative method is developed using near-infrared spectroscopy (NIRS). NIRS
      signals are measured at 44 positions (22 on each side) on the fronto-temporal
      areas in 20 patients with cerebral ischemia. In order to extract the pulse-wave
      component, the raw total hemoglobin data recorded from each position are band
      pass filtered (0.8 to 2.0 Hz) and subjected to a fast Fourier transform to obtain
      the power spectrum of the pulse wave. The ischemic region is determined by single
      photon emission computed tomography. The pulse-wave power in the ischemic region
      is compared with that in the symmetrical region on the contralateral side. In 17
      cases (85%), the pulse-wave power on the ischemic side is significantly lower
      than that on the contralateral side, which indicates that the transmission of the
      pulse wave is attenuated in the region with reduced blood flow. Pulse-wave power
      might be useful as a noninvasive marker of cerebral ischemia.

PMID- 24084857
TI  - Versatile solid-state coordination chemistry of telluroether complexes of
      silver(I) and copper(I).
AB  - The treatment of EPh2 (E = Te, Se) with Ag(O3SCF3) or Cu(O3SCF3).1/2C6H6 in
      dichloromethane yields isomorphous complexes [Ag(TePh2)3](O3SCF3) (1),
      [Cu(TePh2)3](O3SCF3) (2), and [Cu(SePh2)3](O3SCF3) (3). The related reaction of
      TeTh2 (Th = 2-thienyl, C4H3S) with Cu(O3SCF3).1/2C6H6 affords
      [Cu(TeTh2)3](O3SCF3) (4). While not isomorphic with 1-3, its crystal structure
      bears a close relationship with them. The reaction of TeTh2 or SePh2 with
      Ag(O3SCF3) yields [Ag(TeTh2)2](O3SCF3) (5) and [Ag(SePh2)2](O3SCF3) (6),
      respectively. They form dinuclear complexes, the silver centers of which are
      coordinated to two terminal R2E ligands and linked together by two bridging
      CF3SO3(-) ligands. The dinuclear complexes further form supramolecular networks
      through pi-pi stacks of the aromatic rings. The treatment of Ag(O3SCF3) with
      Te(CH2SiMe3)2 results in the formation of a mixture containing polynuclear
      [Ag{Ag[Te(CH2SiMe3)2]}4]n(O3SCF3)5n (7) and [Ag{Te(CH2SiMe3)2}]n(O3SCF3)n (8).
      The cyclic repeating units in 7 are connected to polymeric chains by two bridging
      CF3SO3(-) ligands. 8 contains a [-Ag-Te(CH2SiMe3)2-]n polymer. There are only
      weak van der Waals interactions between the polymer chains of 7 and 8. 

PMID- 24084858
TI  - Electrochemically shape-controlled synthesis in deep eutectic solvents: triambic
      icosahedral platinum nanocrystals with high-index facets and their enhanced
      catalytic activity.
AB  - Pt triambic icosahedral nanocrystals (TIH NCs) enclosed by {771} high-index
      facets were successfully synthesized electrochemically, for the first time, in
      ChCl-urea based deep eutectic solvents, and exhibited higher electrocatalytic
      activity and stability towards ethanol electrooxidation than a commercial Pt
      black catalyst. 

PMID- 24084856
TI  - Two-photon fluorescence imaging of intracellular hydrogen peroxide with
      chemoselective fluorescent probes.
AB  - We present the application of two-photon fluorescence (TPF) imaging to monitor
      intracellular hydrogen peroxide (H2O2) production in brain cells. For selective
      imaging of H2O2 over other reactive oxygen species, we employed small-molecule
      fluorescent probes that utilize a chemoselective boronate deprotection mechanism.
      Peroxyfluor-6 acetoxymethyl ester detects global cellular H2O2 and mitochondria
      peroxy yellow 1 detects mitochondrial H2O2. Two-photon absorption cross sections
      for these H2O2 probes are measured with a mode-locked Ti:sapphire laser in the
      wavelength range of 720 to 1040 nm. TPF imaging is demonstrated in the HT22 cell
      line to monitor both cytoplasmic H2O2 and localized H2O2 production in
      mitochondria. Endogenous cytoplasmic H2O2 production is detected with TPF imaging
      in rat astrocytes modified with d-amino acid oxidase. The TPF H2O2 imaging
      demonstrated that these chemoselective probes are powerful tools for the
      detection of intracellular H2O2.

PMID- 24084859
TI  - Making a knockout mouse: From stem cells to embryos.

PMID- 24084861
TI  - TSC on the peroxisome controls mTORC1.
AB  - mTOR is a central controller that integrates many inputs to regulate cell growth
      and ensure cellular homeostasis. The mTORC1 inhibitor TSC (tuberous sclerosis
      complex) on the peroxisome is found to inhibit mTORC1 in response to endogenous
      reactive oxygen species. Thus, mTOR may avoid confounding different inputs by
      sensing them at different cellular locations. 

PMID- 24084862
TI  - Q-bodies monitor the quinary state of the protein fold.
AB  - Cytoplasmic compartments containing misfolded proteins targeted for degradation,
      named Q-bodies, have been identified. Q-body formation is a dynamic process that
      actively manages the metastable state of the protein fold through small heat
      shock proteins and the Hsp70-Hsp90-Hsp110 proteostasis system to promote cellular
      fitness under both physiological and stress conditions. 

PMID- 24084863
TI  - SON sheds light on RNA splicing and pluripotency.
AB  - The role of RNA splicing in the regulation of stem cell properties has remained
      largely unexplored. The splicing-associated protein SON is now shown to be
      necessary for embryonic stem cell maintenance, by influencing the splicing of
      pluripotency regulators. 

PMID- 24084866
TI  - Understanding oscillatory phenomena in molecular hydrogen generation via sodium
      borohydride hydrolysis.
AB  - The hydrolysis of borohydride salts represents one of the most promising
      processes for the generation of high purity molecular hydrogen under mild
      conditions. In this work we show that the sodium borohydride hydrolysis exhibits
      a fingerprinting periodic oscillatory transient in the hydrogen flow over a wide
      range of experimental conditions. We disproved the possibility that flow
      oscillations are driven by supersaturation phenomena of gaseous bubbles in the
      reactive mixture or by a nonlinear thermal feedback according to a thermokinetic
      model. Our experimental results indicate that the NaBH4 hydrolysis is a
      spontaneous inorganic oscillator, in which the hydrogen flow oscillations are
      coupled to an "oscillophor" in the reactive solution. The discovery of this
      original oscillator paves the way for a new class of chemical oscillators, with
      fundamental implications not only for testing the general theory on oscillations,
      but also with a view to chemical control of borohydride systems used as a source
      of hydrogen based green fuel. 

PMID- 24084867
TI  - Image cytometry protocols.

PMID- 24084868
TI  - Authors' response to letter to the editor on "image cytometry protocols".

PMID- 24084870
TI  - Exploring TCGA Pan-Cancer data at the UCSC Cancer Genomics Browser.
AB  - The UCSC Cancer Genomics Browser (https://genome-cancer.ucsc.edu) offers
      interactive visualization and exploration of TCGA genomic, phenotypic, and
      clinical data, as produced by the Cancer Genome Atlas Research Network.
      Researchers can explore the impact of genomic alterations on phenotypes by
      visualizing gene and protein expression, copy number, DNA methylation, somatic
      mutation and pathway inference data alongside clinical features, Pan-Cancer
      subtype classifications and genomic biomarkers. Integrated Kaplan-Meier survival
      analysis helps investigators to assess survival stratification by any of the
      information. 

PMID- 24084871
TI  - Structural evolution of calcite at high temperatures: phase V unveiled.
AB  - The calcite form of calcium carbonate CaCO3 undergoes a reversible phase
      transition between Rc and Rm at ~1240 K under a CO2 atmosphere of ~0.4 MPa. The
      joint probability density function obtained from the single-crystal X-ray
      diffraction data revealed that the oxygen triangles of the CO3 group in the high
      temperature form (Phase V) do not sit still at specified positions in the space
      group Rm, but migrate along the undulated circular orbital about carbon. The
      present study also shows how the room temperature form (Phase I) develops into
      Phase V through an intermediate form (Phase IV) in the temperature range between
      ~985 K and ~1240 K.

PMID- 24084872
TI  - Assessment of mercury bioavailability to benthic macroinvertebrates using
      diffusive gradients in thin films (DGT).
AB  - Mercury-specific diffusive gradient in thin films (DGTs) were used in laboratory
      microcosms as a biomonitoring tool to assess the lability of mercury (Hg) total
      and monomethylmercury Hg (MeHg), and to develop a relationship between chemical
      lability and bioavailability in estuarine sediments. Time-series deployment of
      DGTs in sediments showed that sediment-bound MeHg is more labile than sediment
      bound inorganic Hg. In subsequent experiments, DGTs were deployed simultaneously
      with three benthic macroinvertebrates (the estuarine amphipod, Leptocheirus
      plumulosus; the estuarine polychaete, Nereis virens; and the marine clam, Macoma
      nasuta) in sediments for up to 55 days. All organisms and their co-deployed DGTs
      exhibited an initial period of rapid Hg uptake followed by slower uptake reaching
      apparent steady state. Strong correlative relationships were generally observed
      between paddle-type DGTs and macroinvertebrate tissue data (r(2) between 0.57 and
      0.97). Further, %MeHg:Total Hg ratios for M. nasuta and N. virens (38.5 +/- 12.2
      and 19.2 +/- 5.2) were similar to their corresponding ratios for the DGTs (33.1
      +/- 13.3 and 24.4 +/- 11.0), and they were significantly higher than the same
      ratios for sediment (2.9 +/- 0.3) and pore water (8.5 +/- 4.9). The %MeHg:Total
      Hg ratios for L. plumulosus (68.5 +/- 6.2) were significantly higher than those
      for the DGTs. This may be because the tissue and DGT data for this organism were
      not truly co-located as L. plumulosus burrows close to the sediment surface, and
      the DGTs sampled the sediment surface. Overall, our results suggest that for
      benthic macroinvertebrates in estuarine sediments studied here, (a) sediment MeHg
      is more bioavailable than inorganic Hg, (b) sediment and pore-water concentration
      measurements are not good predictors for the extent of bioaccumulation of Hg
      species, and (c) DGTs are an effective biomonitoring tool for the assessment of
      bioavailability of Hg species. 

PMID- 24084873
TI  - Postmortem redistribution of tramadol and O-desmethyltramadol.
AB  - Tramadol is a widely used analgesic opioid for moderate-to-severe pain due to its
      efficacy and safety. Although tramadol induces less adverse effects compared with
      other opioids, an increased number of documented cases of dependence, abuse,
      intentional overdose or intoxication have been described. In fatal intoxication,
      the interpretation of the probable cause of death often relies on the measurement
      of the tramadol concentration in blood. However, postmortem redistribution (PMR)
      may affect the results and therefore bias the autopsy report. In the present
      study, the postmortem cardiac and femoral blood samples from 15 cases of fatal
      tramadol intoxication were obtained to assess the PMR of tramadol and its main
      active metabolite, O-desmethyltramadol (M1). Toxicological analysis was performed
      by the gas chromatography-electron impact-mass spectrometry (GC-EI-MS) method,
      previously developed and validated for the quantification of both analytes. The
      cardiac-to-femoral blood ratios of 1.40 and 1.28 were obtained for tramadol and
      M1, respectively. Results were compared with those in the literature and it was
      possible to conclude that femoral blood should be considered for quantitative
      interpretations in fatal cases of tramadol intoxication. 

PMID- 24084874
TI  - Screening and confirmation of 62 drugs of abuse and metabolites in urine by ultra
      high-performance liquid chromatography-quadrupole time-of-flight mass
      spectrometry.
AB  - An ultra-high-performance liquid chromatography--quadrupole time-of-flight mass
      spectrometry (UHPLC-QTOF-MS) method for the screening and confirmation of 62
      drugs of abuse and their metabolites in urine was developed in this study. The
      most commonly abused drugs, including amphetamines, opioids, cocaine,
      benzodiazepines (BZDs) and barbiturates, and many other new and emerging abused
      drugs, were selected as the analytes for this study. Urine samples were diluted 5
      fold with deionized water before analysis. Using a superficially porous micro
      particulate column and an acetic acid-based mobile phase, 54 basic and 8 acidic
      analytes could be detected within 15 and 12 min in positive and negative
      ionization modes, respectively. The MS collision energies for the 62 analytes
      were optimized, and their respective fragmentation patterns were constructed in
      the in-house library for confirmatory analysis. The coefficients of variation of
      the intra- and inter-day precision of the analyte responses all were <17.39%. All
      analytes, except barbital, showed matrix effects of 77-121%. The limits of
      detection of the 62 analytes were between 2.8 and 187.5 ng/mL, which were lower
      than their respective cut-off concentrations (20-500 ng/mL). Ten urine samples
      from patients undergoing methadone treatment were analyzed by the developed UHPLC
      QTOF-MS method, and the results were compared with the immunoassay method.

PMID- 24084875
TI  - The history of barbed sutures.
AB  - Ligatures have been used for millennia to close wounds. Sterilization and
      synthetic polymers that degrade in a commensurate fashion with wound healing have
      been the most significant improvements in these age-old devices. However, the
      constricting loop of a traditional suture and subsequent ischemia ("approximate,
      don't strangulate") still account for the most common cause of wound dehiscence
      necrosis. Inspired by the quill of the North American porcupine, I envisioned a
      bidirectional array of barbs that could secure tissue without relying on
      constricting loops. One set of barbs could anchor the other. In this article, I
      document the development process of these barbed sutures from concept to patent
      to manufacture and US Food and Drug Administration approval. Knotless, strong,
      and easy to place, barbed sutures could foreseeably supplant conventional
      sutures, particularly as endoscopic procedures become more common. They also
      offer the intriguing potential to suspend ptotic tissues without surgical
      intervention. 

PMID- 24084876
TI  - Barbed sutures in aesthetic plastic surgery: evolution of thought and process.
AB  - The evolution of barbed suture technologies and their application in the field of
      plastic surgery is now in its third decade. Much has been learned along the way.
      Initial excitement was often followed by disappointment as we learned more about
      the limited longevity of minimally invasive procedures and complications arising
      from various suture designs of the past. Some of the early designs, developed
      primarily for use in aesthetic facial procedures, included free-floating,
      bidirectionally barbed, nonabsorbable sutures; unidirectional barbed,
      nonabsorbable sutures; anchored, bidirectional, nonabsorbable double-threaded
      sutures; and a technology combining a nonabsorbable knotted thread and absorbable
      cones. More recently, a new, absorbable, unidirectional barbed suture design has
      become available. However, it should be noted that very limited data are
      available for any of the modified suture designs used in this field, and much of
      what has been published is based on the experience of a single user. The author
      has used the bidirectionally barbed Quill Knotless Tissue-Closure Device
      (Angiotech Pharmaceuticals, Inc, Vancouver, British Columbia, Canada), the most
      common barbed suture in both facial and other aesthetic plastic surgery
      procedures, with considerable success in various open aesthetic facial
      procedures, including suspension of the brow and midface, platysmaplasty, and
      lateral neck suspension. It is the author's experience that completion of 1 to 2
      cases with this technology is sufficient to achieve competency in the closure
      techniques discussed in this article and that time savings can be realized using
      this device in various breast and body contouring procedures, including
      mastopexy, reduction mammoplasty, abdominoplasty, bodylift, and brachioplasty. 

PMID- 24084877
TI  - Barbed sutures in plastic surgery: a personal experience.
AB  - Secure closure of wounds is vital to any plastic surgery procedure. Recent
      developments in suture design have incorporated the creation of small barbs along
      the suture strand that are intended to engage the surrounding soft tissue and
      "lock" the suture (and, therefore, the wound closure) into place. Early
      experience with this type of modified suture has shown promise for a host of
      wound closure indications, including the closure of skin and fat as well as
      superficial and deep fascia. Advantages include secure wound closure, elimination
      of the need for a "third hand," decreased operative time, and an improved
      appearance in cutaneous scars. 

PMID- 24084878
TI  - Barbed sutures in breast reconstruction.
AB  - Postoperative closure techniques in breast reconstruction have remained largely
      unchanged over the past 75 years, despite recent use of adhesives and
      subcuticular staples and the advent of self-anchoring barbed sutures. In this
      article, the author discusses the applications for barbed sutures in breast
      reconstruction and describes specific techniques. Innovations in barbed suture
      material are also described, and the author's personal experiences are presented
      in comparison with traditional suturing techniques. 

PMID- 24084879
TI  - Quill barbed sutures in body contouring surgery: a 6-year comparison with running
      absorbable braided sutures.
AB  - BACKGROUND: Body contouring operations are concluded with suture closure of long
      incisions under tension. While an expeditious and secure repair without
      complications is the objective, wound closure typically consumes a substantial
      percentage of the operative time and too often leads to delayed wound healing and
      other problems. OBJECTIVES: The authors evaluate suture-line wound healing for
      body contouring operations with barbed suture wound closure compared with
      absorbable running suture closure. METHODS: In this retrospective study, wound
      healing complications for a 228 consecutive-patient cohort with barbed sutures
      over a period of 4 years were compared with those for a prior 132 consecutive
      patient cohort with absorbable running sutures over a period of 2 years.
      Complications were classified according to severity: grade 1 (mild), grade 2
      (moderate), and grade 3 (severe). The preferred suture techniques for the closure
      of either thick or thin subcutaneous tissue under tension are described. The
      authors' clinical impressions are also presented. RESULTS: Patients whose wounds
      were closed with absorbable running sutures had a significantly greater incidence
      of complications at all severity grades of severity than did those with barbed
      suture closures, with the exception of grade 3 (severe) complications in
      thighplasty. Logistical regression was <1, and the confidence interval was also
      <1, in support of these results. CONCLUSIONS: Proper barbed suture selection and
      2-layer technique led to a statistically significant lower rate of wound-healing
      complications as compared with prior experience with traditional running braided
      absorbable sutures. Other benefits were more rapid speed of closure, adequate
      security of the wound closure, and increased surgeon satisfaction. LEVEL OF
      EVIDENCE: 3.

PMID- 24084880
TI  - Barbed sutures in body surgery.
AB  - Wound-closing technology continues to evolve with the advent of barbed sutures,
      which appear to address some of the limitations of traditional sutures (numerous
      knots and time-consuming insertion, among other things). Advantages of knotless
      suture devices, specifically in body contouring, have been discussed in the
      literature over the past decade, with a recent increase over the past several
      years due to the US Food and Drug Administration (FDA) approval of unidirectional
      V-Loc (Covidien, Mansfield, Massachusetts) and bidirectional Quill (Angiotech
      Pharmaceuticals, Inc, Vancouver, British Columbia, Canada) barbed sutures for
      soft tissue approximation. A thorough review of the existing literature and
      evaluation of the author's personal experience are presented in this article. As
      with any new surgical device, a learning curve is present that needs to be
      overcome to realize the full benefits of utilizing barbed sutures in body surgery
      while minimizing their complications. 

PMID- 24084881
TI  - The application of barbed sutures in body contouring surgery.
AB  - Even with the evolution of primary surgical techniques in body contouring, wound
      closure remains primarily traditional and has not advanced beyond the techniques
      followed in past decades. Streamlining wound closure would be the next advance
      for body contouring surgery. Absorbable barbed sutures offer a potential
      solution, and they are the subject of this review investigating the applications
      of absorbable barbed sutures in body contouring surgery. Barbed sutures hold
      tension as closure proceeds, theoretically decreasing the time required for wound
      closure, approximating dead space, and obliterating subcutaneous knots that may
      result in palpable, painful granulomas. Review of the literature reveals some
      evidence of time savings (in some cases significant and, in some, not); however,
      the literature also shows some wound complications from the use of barbed
      sutures, including infections and extrusions. Barbed sutures have not yet been
      conventionally embraced, and the technology will certainly continue to evolve in
      order to make the devices more desirable for plastic surgeons. 

PMID- 24084882
TI  - Incorporating barbed sutures in abdominoplasty.
AB  - Barbed sutures can be used in body contouring procedures to close long incisions
      better than conventional sutures. The results of a literature review focusing on
      the use of barbed sutures in abdominal contouring procedures suggest that they
      are safe and effective in wound closure with complication rates similar to
      conventional sutures but with possibly faster incision-closure times. An update
      on one author's (K.A.G.) personal experience with barbed progressive tension
      sutures in abdominoplasty procedures is presented, along with practical technique
      recommendations for barbed suture use. 

PMID- 24084883
TI  - Introduction to the barbed sutures supplement: the expanding applications of
      barbed sutures.

PMID- 24084884
TI  - Suspension of the gluteal region with silhouette sutures.
AB  - The authors present their minimally invasive gluteopexy technique, using
      polypropylene 2-0 sutures with 10 absorbable polylactic cones in their distal
      section (Silhouette Lift, Irvine, California) to improve the anteroposterior
      projection of the gluteal region. Histological study of the reaction of adipose
      tissue surrounding the cones previously has shown that, 3 months after insertion
      of the sutures, fibrous scar tissue is sufficiently developed to resist the
      weight of the tissues. On the basis of this finding, the authors decided to
      perform the gluteopexy with sutures, in 2 surgical steps. During the first step,
      the sutures are inserted in the adipose tissue without any proximal fixation. In
      the second step, performed 3 months after the first procedure when the fibrous
      reaction is more solid, the sutures are tightened to obtain the gluteopexy. Among
      the advantages of this technique are its simplicity, the fact that it produces no
      traumatic effects, and the fact that it can be performed with local anesthetic,
      reducing surgical time. It is also possible to combine this procedure with
      lipofilling or liposuction techniques. 

PMID- 24084885
TI  - New and emerging uses of barbed suture technology in plastic surgery.
AB  - Barbed sutures first received US Food and Drug Administration approval for soft
      tissue approximation in 2005 and early adopters readily embraced this device to
      develop new techniques. It has become apparent that the advantages are more than
      just "skin deep." Superficial and deep fascia, cartilage, tendon, joint capsule,
      and fibrous periprosthetic capsules can also be manipulated. Barbed sutures have
      revolutionized our approach to facial rejuvenation and body contouring by
      enhancing our ability to quilt and powerfully lift tissue. The elimination of
      surgical drains and shorter surgical times has made this a true boon for plastic
      surgeons as well as many other surgical specialists. This article summarizes some
      of the current and evolving applications of this exciting new tool. 

PMID- 24084886
TI  - The function of human epidermal growth factor receptor-3 and its role in tumors
      (Review).
AB  - Human epidermal growth factor receptor-3 (HER-3) is the third member of the HER
      family. It was previously considered not to contain tyrosine kinase activity and
      catalytic activity and the intracellular region of HER-3 could not bind ATP and
      be auto-phosphorylated. Thus, the clinical value of HER-3 was ignored. Currently,
      biochemical analysis has confirmed that the kinase domain of HER-3 is a specific
      allosteric activator; it acts as a functional activator to activate the recipient
      kinase (HER-1, HER-2, HER-4). With the in-depth knowledge of its structure and
      function, studies on the relationship of HER-3 and human tumors are rapidly
      increasing. HER-3 is closely related to tumorigenesis, progression and
      metastasis. HER-3 is involved in resistance to targeted therapy, and may serve as
      a new therapeutic target. The expression of HER-3 helps to predict prognosis and
      treatment efficacy. HER-3 has become a focus of concern in the HER family and has
      gained significant attention in the search for cancer treatment. 

PMID- 24084887
TI  - Health disparities around the world: perspectives from the 2012 Principles and
      Practice of Cancer Prevention and Control course at the National Cancer
      Institute.
AB  - INTRODUCTION: The National Cancer Institute Principles and Practice of Cancer
      Prevention and Control course is a 4-week course encompassing a variety of cancer
      prevention and control topics that is open to attendees from medical, academic,
      government, and related institutions around the world. Themes related to the
      challenges health disparities present to cancer prevention efforts and potential
      solutions to these issues emerged from facilitated group discussions among the
      2012 course participants. MATERIALS AND METHODS: Small-group discussion sessions
      with participants (n = 85 from 33 different countries) and facilitators (n = 9)
      were held once per week throughout the 4-week course. Facilitators prepared open
      ended questions related to course topics. Participants provided responses
      reflecting their opinions of topics on the basis of experiences in their
      countries. A thematic analysis was conducted to explore themes emerging from the
      discussion groups. RESULTS: The varied influences of health disparities on cancer
      prevention efforts among > 30 countries represented prominent themes across
      discussion groups. Participants discussed the interplay of individual
      characteristics, including knowledge and culture, interpersonal relationships
      such as family structure and gender roles, community and organizational factors
      such as unequal access to health care and access to treatment, and national-level
      factors including policy and government structure. CONCLUSION: The ideas and
      solutions presented here are from a geographically and professionally diverse
      group of individuals. The collective discussion highlighted the pervasiveness of
      health disparities across all areas represented by course participants and
      suggested that disparities are the largest impediment to achieving cancer
      prevention goals.

PMID- 24084888
TI  - Private payers and cancer care: land of opportunity.
AB  - The costs of cancer care are unsustainable in the present US health care system.
      Private payers have taken a leading role in oncology payment reform. This
      benefits all payers, including the Center for Medicare and Medicaid Services
      (CMS). Private payers' ability to set up systems of measurement and quality
      improvement is a strategy to support pay-for-value contracting. This facilitates
      workflow changes in oncology office practice as a way to bend the cost trends
      while enhancing patient care. Oncology practitioners demand speed and flexibility
      in deploying customized information technology solutions in exchange for new
      contracting terms. Pathway and guideline support tools have been proven effective
      in validating the use of evidence-based medicine and in systematizing office
      operations to reduce avoidable costs. The future of oncology practice should see
      further enhancement of these capabilities. A common health information exchange
      pipeline will allow patients, physicians, and other health care providers to
      share structured information from multiple electronic medical record/electronic
      health record platforms. By allowing multiple payers, including CMS, to access
      commonly accepted clinical decision support rules, any payer can create contracts
      and relationships with oncology practices. In this manner, future changes in
      payment for oncology services mandated by CMS can be sustained within the
      infrastructures being built today through payer-provider collaborations. 

PMID- 24084889
TI  - Crucial role of the biological barrier at the primary targeted organs in
      controlling the translocation and toxicity of multi-walled carbon nanotubes in
      the nematode Caenorhabditis elegans.
AB  - Multi-walled carbon nanotubes (MWCNTs) can be translocated into the targeted
      organs of organisms. We employed a model organism of the nematode Caenorhabditis
      elegans to investigate the role of a biological barrier at the primary targeted
      organs in regulating the translocation and toxicity formation of MWCNTs. A
      prolonged exposure to MWCNTs at predicted environmental relevant concentrations
      caused adverse effects associated with both the primary and secondary targeted
      organs on nematodes. The function of PEGylated modification in reducing MWCNTs
      toxicity might be mainly due to the suppression of their translocation into
      secondary targeted organs through the primary targeted organs. A biological
      barrier at the primary targeted organs contributed greatly to the control of
      MWCNTs translocation into secondary targeted organs, as indicated by functions of
      Mn-SODs required for prevention of oxidative stress in the primary targeted
      organs. Over-expression of Mn-SODs in primary targeted organs effectively
      suppressed the translocation and toxicity of MWCNTs. Our work highlights the
      crucial role of the biological barrier at the primary targeted organs in
      regulating the translocation and toxicity formation of MWCNTs. Our data also shed
      light on the future development of engineered nanomaterials (ENMs) with improved
      biocompatibility and design of prevention strategies against ENMs toxicity. 

PMID- 24084890
TI  - All fiber optics circular-state swept source polarization-sensitive optical
      coherence tomography.
AB  - A swept source (SS)-based circular-state (CS) polarization-sensitive optical
      coherence tomography (PS-OCT) constructed entirely with polarization-maintaining
      fiber optics components is proposed with the experimental verification. By means
      of the proposed calibration scheme, bulk quarter-wave plates can be replaced by
      fiber optics polarization controllers to, therefore, realize an all-fiber optics
      CS SSPS-OCT. We also present a numerical dispersion compensation method, which
      can not only enhance the axial resolution, but also improve the signal-to-noise
      ratio of the images. We demonstrate that this compact and portable CS SSPS-OCT
      system with an accuracy comparable to bulk optics systems requires less stringent
      lens alignment and can possibly serve as a technology to realize PS-OCT
      instrument for clinical applications (e.g., endoscopy). The largest deviations in
      the phase retardation (PR) and fast-axis (FA) angle due to sample probe in the
      linear scanning and a rotation angle smaller than 65 deg were of the same order
      as those in stationary probe setups. The influence of fiber bending on the
      measured PR and FA is also investigated. The largest deviations of the PR were
      3.5 deg and the measured FA change by ~12 to 21 deg. Finally, in vivo imaging of
      the human fingertip and nail was successfully demonstrated with a linear scanning
      probe.

PMID- 24084891
TI  - Regional population collapse followed initial agriculture booms in mid-Holocene
      Europe.
AB  - Following its initial arrival in SE Europe 8,500 years ago agriculture spread
      throughout the continent, changing food production and consumption patterns and
      increasing population densities. Here we show that, in contrast to the steady
      population growth usually assumed, the introduction of agriculture into Europe
      was followed by a boom-and-bust pattern in the density of regional populations.
      We demonstrate that summed calibrated radiocarbon date distributions and
      simulation can be used to test the significance of these demographic booms and
      busts in the context of uncertainty in the radiocarbon date calibration curve and
      archaeological sampling. We report these results for Central and Northwest Europe
      between 8,000 and 4,000 cal. BP and investigate the relationship between these
      patterns and climate. However, we find no evidence to support a relationship. Our
      results thus suggest that the demographic patterns may have arisen from
      endogenous causes, although this remains speculative. 

PMID- 24084892
TI  - Long-lived excited states in i-motif DNA studied by picosecond time-resolved IR
      spectroscopy.
AB  - The transient IR absorption spectrum for UV-excited i-motif DNA is reported for
      the first time and found to possess complex dynamics pointing to multiple decay
      processes, including possible charge transfer between packed hemi-protonated C
      bases. 

PMID- 24084894
TI  - Computational study of the mechanism of half-reactions in class 1A dihydroorotate
      dehydrogenase from Trypanosoma cruzi.
AB  - Chagas' disease is considered to be a health problem affecting millions of people
      in Latin America. This disease is caused by the parasite Trypanosoma cruzi.
      Recently dihydroorotate dehydrogenase class 1A from Trypanosoma cruzi (TcDHODA)
      was shown to be essential for the survival and growth of T. cruzi and proposed as
      a drug target against Chagas' disease. This enzyme catalyzes the oxidation of (S)
      dihydroorotate to orotate, with a proposed catalytic cycle consisting of two half
      reactions. In the first half-reaction dihydroorotate is oxidized to orotate, with
      the consequent reduction of the flavin mononucleotide cofactor. In the second
      half-reaction fumarate is reduced to succinate. The first oxidation half-reaction
      may occur via a concerted or a stepwise mechanism. Herein, the catalytic
      mechanism of TcDHODA has been studied using hybrid Quantum Mechanical/Molecular
      Mechanical (QM/MM) Molecular Dynamics (MD) simulations. The free energy profiles
      derived from the bidimensional potential of mean force reveal more details for
      two half-reaction processes. 

PMID- 24084895
TI  - Predictors of treatment completion in a sample of youth who have experienced
      physical or sexual trauma.
AB  - Despite significant advances in knowledge and availability of evidence-based
      models for child traumatic stress, many children simply do not complete
      treatment. There remain notable gaps in the services research literature about
      treatment completion among youth, particularly those who have experienced trauma
      and related sequelae. This study investigated the linkages among child physical
      and sexual trauma, posttraumatic stress disorder (PTSD) symptomatology, and
      treatment completion utilizing a clinical sample drawn from a large database from
      community treatment centers across the United States specializing in childhood
      trauma. Results from regression analyses indicated that neither the experience of
      sexual nor physical trauma directly predicted successful treatment completion.
      The links between sexual trauma and treatment completion, however, were mediated
      by PTSD avoidance symptoms. Children and youth experiencing sexual trauma
      reported higher levels of avoidance symptoms that were, in turn, significantly
      associated with a lower likelihood of completing trauma-focused mental health
      treatment. Practice implications are discussed and include strategies for
      clinicians to intervene during pivotal points of treatment to improve rates of
      service utilization and treatment completion. 

PMID- 24084897
TI  - Photocatalysts with internal electric fields.
AB  - The photocatalytic activity of materials for water splitting is limited by the
      recombination of photogenerated electron-hole pairs as well as the back-reaction
      of intermediate species. This review concentrates on the use of electric fields
      within catalyst particles to mitigate the effects of recombination and back
      reaction and to increase photochemical reactivity. Internal electric fields in
      photocatalysts can arise from ferroelectric phenomena, p-n junctions, polar
      surface terminations, and polymorph junctions. The manipulation of internal
      fields through the creation of charged interfaces in hierarchically structured
      materials is a promising strategy for the design of improved photocatalysts. 

PMID- 24084898
TI  - miR-205 promotes the growth, metastasis and chemoresistance of NSCLC cells by
      targeting PTEN.
AB  - Non-small cell lung cancer (NSCLC) is one of the most common causes of cancer
      related mortality worldwide. microRNAs (miRNAs) play critical roles in
      carcinogenesis. miR-205 has been shown to be upregulated in NSCLC. In the present
      study, we identified the promotive effects of miR-205 on various significant
      biological properties of NSCLC cells, and confirmed the regulation of PTEN by miR
      205. The expression of miR-205 was examined by quantitative real-time PCR both in
      NSCLC cell lines and tissues. The effect of miR-205 on PTEN expression was
      assessed in NSCLC cell lines with miR-205 mimics/inhibitor to elevate/decrease
      miR-205 expression. Furthermore, the roles of miR-205 in regulating the
      biological properties of NSCLC cells, including growth, invasion and
      chemoresistance, were assayed using miR-205 mimic/inhibitor-transfected cells.
      The 3'-untranslated region (3'-UTR) of PTEN combined with miR-205 and this was
      confirmed by luciferase reporter assay and western blotting. miR-205 expression
      was increased in NSCLC cell lines as well as in tissues. Overexpression of miR
      205 promoted growth, migration and invasion, and enhanced the chemoresistance of
      NSCLC cells. Luciferase activity and western blotting demonstrated that miR-205
      negatively regulated PTEN at a posttranscriptional level. However, miR-205
      knockdown suppressed these processes in A549 cells and increased the expression
      of PTEN protein. Furthermore, overexpression of PTEN exhibited effects identical
      with those of the miR-205 inhibitor in NSCLC cells. Our results demonstrated that
      miR-205 is involved in the tumorigenesis of NSCLC through modulation of the PTEN
      signaling pathway. 

PMID- 24084901
TI  - Dark passage: Dorothy Dehner.

PMID- 24084902
TI  - Malaria vaccine, Ebola therapy promising in early studies.

PMID- 24084903
TI  - Survey finds physicians rarely advise use of sunscreen to patients, even those
      most at risk for skin cancer.

PMID- 24084904
TI  - Researchers seek to uncover root causes of delayed treatment and diagnosis in the
      outpatient setting.

PMID- 24084905
TI  - USPSTF: Primary care clinicians can help curb tobacco use in youths.

PMID- 24084915
TI  - How the Pioneer ACO Model needs to change: lessons from its best-performing ACO.

PMID- 24084916
TI  - Pricing for orphan drugs: will the market bear what society cannot?

PMID- 24084917
TI  - Investing in evidence-based care for the severely mentally ill.

PMID- 24084918
TI  - A piece of my mind. What's in a name?

PMID- 24084919
TI  - The Women's Health Initiative--a victory for women and their health.

PMID- 24084920
TI  - Weighing in on opioids for chronic pain: the barriers to change.

PMID- 24084922
TI  - Chronic use of opioid medications before and after bariatric surgery.
AB  - IMPORTANCE: Obesity is associated with chronic noncancer pain. It is not known if
      opioid use for chronic pain in obese individuals undergoing bariatric surgery is
      reduced. OBJECTIVES: To determine opioid use following bariatric surgery in
      patients using opioids chronically for pain control prior to their surgery and to
      determine the effect of preoperative depression, chronic pain, or postoperative
      changes in body mass index (BMI) on changes in postoperative chronic opioid use.
      DESIGN, SETTING, AND PARTICIPANTS: Retrospective cohort study in a distributed
      health network (10 demographically and geographically varied US health care
      systems) of 11,719 individuals aged 21 years and older, who had undergone
      bariatric surgery between 2005 and 2009, and were assessed 1 year before and
      after surgery, with latest follow-up by December 31, 2010. MAIN OUTCOMES AND
      MEASURES: Opioid use, measured as morphine equivalents 1 year before and 1 year
      after surgery, excluding the first 30 postoperative days. Chronic opioid use is
      defined as 10 or more opioid dispensings over 90 or more days or as dispensings
      of at least a 120-day supply of opioids during the year prior to surgery.
      RESULTS: Before surgery, 8% (95% CI, 7%-8%; n = 933) of bariatric patients were
      chronic opioid users. Of these individuals, 77% (95% CI, 75%-80%; n = 723)
      continued chronic opioid use in the year following surgery. Mean daily morphine
      equivalents for the 933 bariatric patients who were chronic opioid users before
      surgery were 45.0 mg (95% CI, 40.0-50.1) preoperatively and 51.9 mg (95% CI, 46.0
      57.8) postoperatively (P < .001). For this group with chronic opiate use prior to
      surgery, change in morphine equivalents before vs after surgery did not differ
      between individuals with loss of more than 50% excess BMI vs those with 50% or
      less (>50% BMI loss: adjusted incidence rate ratio [adjusted IRR, 1.17; 95% CI,
      1.07-1.28] vs <=50% BMI loss [adjusted IRR, 1.03; 95% CI, 0.93-1.14] model
      interaction, P = .06). In other subgroup analyses of preoperative chronic opioid
      users, changes in morphine equivalents before vs after surgery did not differ
      between those with or without preoperative diagnosis of depression or chronic
      pain (depression only [n = 75; IRR, 1.08; 95% CI, 0.90-1.30]; chronic pain only
      [n = 440; IRR, 1.17; 95% CI, 1.08-1.27]; both depression and chronic pain [n =
      226; IRR, 1.11; 95% CI, 0.96-1.28]; neither depression nor chronic pain [n = 192;
      IRR, 1.22; 95% CI, 0.98-1.51); and P values for model interactions when compared
      with neither were P = .42 for depression, P = .76 for pain, and P = .48 for both.
      CONCLUSIONS AND RELEVANCE: In this cohort of patients who underwent bariatric
      surgery, 77% of patients who were chronic opioid users before surgery continued
      chronic opioid use in the year following surgery, and the amount of chronic
      opioid use was greater postoperatively than preoperatively. These findings
      suggest the need for better pain management in these patients following surgery.

PMID- 24084923
TI  - Association of national initiatives to improve cardiac arrest management with
      rates of bystander intervention and patient survival after out-of-hospital
      cardiac arrest.
AB  - IMPORTANCE: Out-of-hospital cardiac arrest is a major health problem associated
      with poor outcomes. Early recognition and intervention are critical for patient
      survival. Bystander cardiopulmonary resuscitation (CPR) is one factor among many
      associated with improved survival. OBJECTIVE: To examine temporal changes in
      bystander resuscitation attempts and survival during a 10-year period in which
      several national initiatives were taken to increase rates of bystander
      resuscitation and improve advanced care. DESIGN, SETTING, AND PARTICIPANTS:
      Patients with out-of-hospital cardiac arrest for which resuscitation was
      attempted were identified between 2001 and 2010 in the nationwide Danish Cardiac
      Arrest Registry. Of 29,111 patients with cardiac arrest, we excluded those with
      presumed noncardiac cause of arrest (n = 7390) and those with cardiac arrests
      witnessed by emergency medical services personnel (n = 2253), leaving a study
      population of 19,468 patients. MAIN OUTCOMES AND MEASURES: Temporal trends in
      bystander CPR, bystander defibrillation, 30-day survival, and 1-year survival.
      RESULTS: The median age of patients was 72 years; 67.4% were men. Bystander CPR
      increased significantly during the study period, from 21.1% (95% CI, 18.8%-23.4%)
      in 2001 to 44.9% (95% CI, 42.6%-47.1%) in 2010 (P < .001), whereas use of
      defibrillation by bystanders remained low (1.1% [95% CI, 0.6%-1.9%] in 2001 to
      2.2% [95% CI, 1.5%-2.9%] in 2010; P = .003). More patients achieved survival on
      hospital arrival (7.9% [95% CI, 6.4%-9.5%] in 2001 to 21.8% [95% CI, 19.8%-23.8%]
      in 2010; P < .001). Also, 30-day survival improved (3.5% [95% CI, 2.5%-4.5%] in
      2001 to 10.8% [95% CI, 9.4%-12.2%] in 2010; P < .001), as did 1-year survival
      (2.9% [95% CI, 2.0%-3.9%] in 2001 to 10.2% [95% CI, 8.9%-11.6%] in 2010; P <
      .001). Despite a decrease in the incidence of out-of-hospital cardiac arrests
      during the study period (40.4 to 34.4 per 100,000 persons in 2001 and 2010,
      respectively; P = .002), the number of survivors per 100,000 persons increased
      significantly (P < .001). For the entire study period, bystander CPR was
      positively associated with 30-day survival, regardless of witnessed status (30
      day survival for nonwitnessed cardiac arrest, 4.3% [95% CI, 3.4%-5.2%] with
      bystander CPR and 1.0% [95% CI, 0.8%-1.3%] without; odds ratio, 4.38 [95% CI,
      3.17-6.06]). For witnessed arrest the corresponding values were 19.4% (95% CI,
      18.1%-20.7%) vs 6.1% (95% CI, 5.4%-6.7%); odds ratio, 3.74 (95% CI, 3.26-4.28).
      CONCLUSIONS AND RELEVANCE: In Denmark between 2001 and 2010, an increase in
      survival following out-of-hospital cardiac arrest was significantly associated
      with a concomitant increase in bystander CPR. Because of the co-occurrence of
      other related initiatives, a causal relationship remains uncertain.

PMID- 24084921
TI  - Menopausal hormone therapy and health outcomes during the intervention and
      extended poststopping phases of the Women's Health Initiative randomized trials.
AB  - IMPORTANCE: Menopausal hormone therapy continues in clinical use but questions
      remain regarding its risks and benefits for chronic disease prevention.
      OBJECTIVE: To report a comprehensive, integrated overview of findings from the 2
      Women's Health Initiative (WHI) hormone therapy trials with extended
      postintervention follow-up. DESIGN, SETTING, AND PARTICIPANTS: A total of 27,347
      postmenopausal women aged 50 to 79 years were enrolled at 40 US centers.
      INTERVENTIONS: Women with an intact uterus received conjugated equine estrogens
      (CEE; 0.625 mg/d) plus medroxyprogesterone acetate (MPA; 2.5 mg/d) (n = 8506) or
      placebo (n = 8102). Women with prior hysterectomy received CEE alone (0.625 mg/d)
      (n = 5310) or placebo (n = 5429). The intervention lasted a median of 5.6 years
      in CEE plus MPA trial and 7.2 years in CEE alone trial with 13 years of
      cumulative follow-up until September 30, 2010. MAIN OUTCOMES AND MEASURES:
      Primary efficacy and safety outcomes were coronary heart disease (CHD) and
      invasive breast cancer, respectively. A global index also included stroke,
      pulmonary embolism, colorectal cancer, endometrial cancer, hip fracture, and
      death. RESULTS: During the CEE plus MPA intervention phase, the numbers of CHD
      cases were 196 for CEE plus MPA vs 159 for placebo (hazard ratio [HR], 1.18; 95%
      CI, 0.95-1.45) and 206 vs 155, respectively, for invasive breast cancer (HR,
      1.24; 95% CI, 1.01-1.53). Other risks included increased stroke, pulmonary
      embolism, dementia (in women aged >=65 years), gallbladder disease, and urinary
      incontinence; benefits included decreased hip fractures, diabetes, and vasomotor
      symptoms. Most risks and benefits dissipated postintervention, although some
      elevation in breast cancer risk persisted during cumulative follow-up (434 cases
      for CEE plus MPA vs 323 for placebo; HR, 1.28 [95% CI, 1.11-1.48]). The risks and
      benefits were more balanced during the CEE alone intervention with 204 CHD cases
      for CEE alone vs 222 cases for placebo (HR, 0.94; 95% CI, 0.78-1.14) and 104 vs
      135, respectively, for invasive breast cancer (HR, 0.79; 95% CI, 0.61-1.02);
      cumulatively, there were 168 vs 216, respectively, cases of breast cancer
      diagnosed (HR, 0.79; 95% CI, 0.65-0.97). Results for other outcomes were similar
      to CEE plus MPA. Neither regimen affected all-cause mortality. For CEE alone,
      younger women (aged 50-59 years) had more favorable results for all-cause
      mortality, myocardial infarction, and the global index (nominal P < .05 for trend
      by age). Absolute risks of adverse events (measured by the global index) per
      10,000 women annually taking CEE plus MPA ranged from 12 excess cases for ages of
      50-59 years to 38 for ages of 70-79 years; for women taking CEE alone, from 19
      fewer cases for ages of 50-59 years to 51 excess cases for ages of 70-79 years.
      Quality-of-life outcomes had mixed results in both trials. CONCLUSIONS AND
      RELEVANCE: Menopausal hormone therapy has a complex pattern of risks and
      benefits. Findings from the intervention and extended postintervention follow-up
      of the 2 WHI hormone therapy trials do not support use of this therapy for
      chronic disease prevention, although it is appropriate for symptom management in
      some women. TRIAL REGISTRATION: clinicaltrials.gov Identifier: NCT00000611.

PMID- 24084924
TI  - Axillary node interventions in breast cancer: a systematic review.
AB  - IMPORTANCE: Recent data from clinical trials have challenged traditional thinking
      about axillary surgery in patients with breast cancer. OBJECTIVES: To summarize
      evidence regarding the role of axillary interventions (surgical and nonsurgical)
      in breast cancer treatment and to review the association of these axillary
      interventions with recurrence of axillary node metastases, mortality, and
      morbidity outcomes in patients with breast cancer. EVIDENCE REVIEW: Ovid MEDLINE
      (1946-July 2013), Cochrane Database of Systematic Reviews (2005-July 2013),
      Cochrane Database of Abstracts of Reviews of Effects (1994-July 2013), and
      Cochrane Central Register of Controlled Trials (1989-July 2013) were searched for
      publications on axillary interventions in breast cancer. Clinical trials,
      observational studies, and meta-analyses with at least 2-year follow-up were
      included. A total of 1070 publications were reviewed, 17 of which met final
      inclusion criteria. FINDINGS: Partial mastectomy followed by whole breast
      radiation is breast-conserving therapy. For women with no suspicious, palpable
      axillary nodes who undergo breast-conserving therapy, there is little evidence of
      benefit from surgical complete axillary node dissection compared with sentinel
      node biopsy alone. Complete axillary node dissection in patients with no palpable
      lymph nodes, compared with sentinel node biopsy, provides no survival benefit and
      is associated with a 1% to 3% reduction in recurrence of axillary lymph node
      metastases, but is associated with a 14% risk of lymphedema. Surgical axillary
      staging via sentinel node biopsy in patients with benign axillary nodes on
      radiological and clinical examination helps to inform decisions regarding
      adjuvant systemic and radiation therapy. Patients and physicians should tailor
      axillary lymph node interventions to maximize regional disease control and
      minimize morbidity. Complete axillary lymph node dissection is indicated in
      patients who present with palpable or needle biopsy-proven axillary metastases,
      patients with positive sentinel nodes undergoing mastectomy (who do not, as a
      standard, receive adjuvant radiation), patients with more than 3 positive
      sentinel nodes undergoing breast-conserving therapy, and patients not meeting
      eligibility criteria for recent trials establishing the safety of sentinel node
      biopsy alone in patients with breast cancer and metastases in their sentinel
      nodes. CONCLUSION AND RELEVANCE: Available evidence suggests that axillary node
      dissection is associated with more harm than benefit in women undergoing breast
      conserving therapy who do not have palpable, suspicious lymph nodes, who have
      tumors 3.0 cm or smaller, and who have 3 or fewer positive nodes on sentinel node
      biopsy.

PMID- 24084925
TI  - Cranberry products and prevention of urinary tract infections.
AB  - CLINICAL QUESTION: Are cranberry products (juice, tablets, capsules, and syrup)
      associated with prevention of urinary tract infections (UTIs) compared with
      placebo or other treatments? BOTTOM LINE: Cranberry products are not associated
      with prevention of UTIs. However, lack of association of cranberry products with
      a reduced incidence of UTIs in clinical trials may be due to lack of participant
      adherence, lack of sufficient active ingredient in the cranberry product, or lack
      of sufficient statistical power.

PMID- 24084926
TI  - Therapy for mental stress-induced myocardial ischemia.

PMID- 24084927
TI  - Therapy for mental stress-induced myocardial ischemia.

PMID- 24084928
TI  - Therapy for mental stress-induced myocardial ischemia--reply.

PMID- 24084929
TI  - Protection of patients from physician substance misuse.

PMID- 24084930
TI  - Protection of patients from physician substance misuse.

PMID- 24084931
TI  - Protection of patients from physician substance misuse--reply.

PMID- 24084932
TI  - Mortality reporting and pay-for-performance programs.

PMID- 24084933
TI  - Mortality reporting and pay-for-performance programs--reply.

PMID- 24084935
TI  - Horses, women and children.

PMID- 24084936
TI  - JAMA patient page. Constipation.

PMID- 24084937
TI  - Translational symmetry breaking and gapping of heavy-quasiparticle pocket in
      URu2Si2.
AB  - URu2Si2 is a uranium compound that exhibits a so-called 'hidden-order' transition
      at ~17.5 K. However, the order parameter of this second-order transition as well
      as many of its microscopic properties remain unclarified despite considerable
      research. One of the key questions in this regard concerns the type of
      spontaneous symmetry breaking occurring at the transition; although rotational
      symmetry breaking has been detected, it is not clear whether another type of
      symmetry breaking also occurs. Another key question concerns the property of
      Fermi-surface gapping in the momentum space. Here we address these key questions
      by a momentum-dependent observation of electronic states at the transition
      employing ultrahigh-resolution three-dimensional angle-resolved photoemission
      spectroscopy. Our results provide compelling evidence of the spontaneous breaking
      of the lattice's translational symmetry and particle-hole asymmetric gapping of a
      heavy quasiparticle pocket at the transition.

PMID- 24084938
TI  - Enhanced lymphatic transport of bioactive lipids: cell culture study of
      polymethoxyflavone incorporation into chylomicrons.
AB  - Polymethoxyflavones (PMFs) are bioactive flavonoids found in citrus fruits that
      have been shown to have potential health promoting properties. However, their
      application as nutraceuticals in functional foods and beverages is currently
      limited due to their low water solubility and high melting point. The oral
      bioavailability of lipophilic compounds can be enhanced by promoting their
      intestinal lymphatic transport through co-administration with digestible lipids.
      We investigated the effects of chylomicron-mediated intestinal lymphatic
      transport on the bioavailability of 5-hydroxy-6,7,8,3',4'-pentamethoxylflavone (5
      HPMF), one of representative PMFs in Caco-2 cells. Our results demonstrated that
      oleic acid and bile acid promoted secretion of chylomicrons in Caco-2 cells, with
      mean diameter ranged from 70 to 150 nm. The intracellular level of 5-HPMF
      increased 3-fold by co-incubation with the mixed micelle solution. Moreover, the
      basolateral level of 5-HPMF increased 3-fold due to enhanced chylomicron-mediated
      transport. Overall, our results demonstrated for the first time that the
      bioavailability of polymethoxyflavones can be enhanced by promoting their
      incorporation into chylomicrons. 

PMID- 24084940
TI  - Antipsychotics and the gut microbiome: olanzapine-induced metabolic dysfunction
      is attenuated by antibiotic administration in the rat.
AB  - The atypical antipsychotic olanzapine is often associated with serious metabolic
      side effects including weight gain and increased visceral fat. These adverse
      events are a considerable clinical problem and the mechanisms underlying them are
      multifactorial and poorly understood. Growing evidence suggests that the gut
      microbiota has a key role in energy regulation and disease states such as
      obesity. Moreover, we recently showed that chronic olanzapine altered the
      composition of the gut microbiome in the rat. It is thus possible that treatments
      that alter gut microbiota composition could ameliorate olanzapine-induced weight
      gain and associated metabolic syndrome. To this end, we investigated the impact
      of antibiotic-induced alteration of the gut microbiota on the metabolic effects
      associated with chronic olanzapine treatment in female rats. Animals received
      vehicle or olanzapine (2 mg kg(-1) per day) for 21 days, intraperitoneal
      injection, two times daily. Animals were also coadministered vehicle or an
      antibiotic cocktail consisting of neomycin (250 mg kg(-1) per day), metronidazole
      (50 mg kg(-1) per day) and polymyxin B (9 mg kg(-1) per day) by oral gavage,
      daily, beginning 5 days before olanzapine treatment. The antibiotic cocktail
      drastically altered the microbiota of olanzapine-treated rats, and olanzapine
      alone was also associated with an altered microbiota. Coadministration of the
      antibiotic cocktail in olanzapine-treated rats attenuated: body weight gain,
      uterine fat deposition, macrophage infiltration of adipose tissue, plasma free
      fatty acid levels, all of which were increased by olanzapine alone. These results
      suggest that the gut microbiome has a role in the cycle of metabolic dysfunction
      associated with olanzapine, and could represent a novel therapeutic target for
      preventing antipsychotic-induced metabolic disease.

PMID- 24084942
TI  - Modeling fixation locations using spatial point processes.
AB  - Whenever eye movements are measured, a central part of the analysis has to do
      with where subjects fixate and why they fixated where they fixated. To a first
      approximation, a set of fixations can be viewed as a set of points in space; this
      implies that fixations are spatial data and that the analysis of fixation
      locations can be beneficially thought of as a spatial statistics problem. We
      argue that thinking of fixation locations as arising from point processes is a
      very fruitful framework for eye-movement data, helping turn qualitative questions
      into quantitative ones. We provide a tutorial introduction to some of the main
      ideas of the field of spatial statistics, focusing especially on spatial Poisson
      processes. We show how point processes help relate image properties to fixation
      locations. In particular we show how point processes naturally express the idea
      that image features' predictability for fixations may vary from one image to
      another. We review other methods of analysis used in the literature, show how
      they relate to point process theory, and argue that thinking in terms of point
      processes substantially extends the range of analyses that can be performed and
      clarify their interpretation. 

PMID- 24084941
TI  - Functional lacrimal gland regeneration by transplantation of a bioengineered
      organ germ.
AB  - The lacrimal gland has a multifaceted role in maintaining a homeostatic
      microenvironment for a healthy ocular surface via tear secretion. Dry-eye
      disease, which is caused by lacrimal gland dysfunction, is one of the most
      prevalent eye diseases that cause corneal epithelial damage and results in
      significant loss of vision and a reduction in the quality of life. Here we
      demonstrate orthotopic transplantation of bioengineered lacrimal gland germs into
      adult mice with an extra-orbital lacrimal gland defect, a mouse model that mimics
      the corneal epithelial damage caused by lacrimal gland dysfunction. The
      bioengineered lacrimal gland germs and harderian gland germs both develop in vivo
      and achieve sufficient physiological functionality, including tear production in
      response to nervous stimulation and ocular surface protection. This study
      demonstrates the potential for bioengineered organ replacement to functionally
      restore the lacrimal gland. 

PMID- 24084944
TI  - No man is an island.

PMID- 24084945
TI  - [AD/HD and autism in 6-12 year olds].

PMID- 24084946
TI  - [Coercion in nursing--for the sake of whom?].

PMID- 24084947
TI  - [Better anticoagulation therapy?].

PMID- 24084939
TI  - A common biological basis of obesity and nicotine addiction.
AB  - Smoking influences body weight such that smokers weigh less than non-smokers and
      smoking cessation often leads to weight increase. The relationship between body
      weight and smoking is partly explained by the effect of nicotine on appetite and
      metabolism. However, the brain reward system is involved in the control of the
      intake of both food and tobacco. We evaluated the effect of single-nucleotide
      polymorphisms (SNPs) affecting body mass index (BMI) on smoking behavior, and
      tested the 32 SNPs identified in a meta-analysis for association with two smoking
      phenotypes, smoking initiation (SI) and the number of cigarettes smoked per day
      (CPD) in an Icelandic sample (N=34,216 smokers). Combined according to their
      effect on BMI, the SNPs correlate with both SI (r=0.019, P=0.00054) and CPD
      (r=0.032, P=8.0 * 10(-7)). These findings replicate in a second large data set
      (N=127,274, thereof 76,242 smokers) for both SI (P=1.2 * 10(-5)) and CPD (P=9.3 *
      10(-5)). Notably, the variant most strongly associated with BMI (rs1558902-A in
      FTO) did not associate with smoking behavior. The association with smoking
      behavior is not due to the effect of the SNPs on BMI. Our results strongly point
      to a common biological basis of the regulation of our appetite for tobacco and
      food, and thus the vulnerability to nicotine addiction and obesity.

PMID- 24084948
TI  - [The cancer riddle is outdated].

PMID- 24084949
TI  - [Constructed contradictions].

PMID- 24084950
TI  - [Has health policy ended up on a side track?].

PMID- 24084951
TI  - [Increase cooperation instead].

PMID- 24084952
TI  - [Boycott of academic cooperation with China].

PMID- 24084953
TI  - [O.E. Iversen replies].

PMID- 24084954
TI  - [Physicians and traffic safety--experiences from More and Romsdal].

PMID- 24084955
TI  - [Relationship between short PhD:s and narrow topic selection?].

PMID- 24084958
TI  - [Bacteria and other microorganisms].

PMID- 24084964
TI  - [Pelvic reservoir--sporadic surgery should be centralized].

PMID- 24084965
TI  - [Questionable effects of electroconvulsive therapy].

PMID- 24084968
TI  - Differences across counties in the registered prevalence of autism, ADHD,
      epilepsy and cerebral palsy in Norway.
AB  - BACKGROUND: In 2012, we published an overview of the prevalence of developmental
      disorders and neurological diseases in children in Norway, which was unknown at
      the time. In this article we will compare diagnostics and treatment across
      counties and institutions. MATERIAL AND METHOD: The prevalence across counties of
      autism spectrum disorders, ADHD, epilepsy and cerebral palsy in children aged 0
      12 was estimated with the aid of data from the Norwegian Patient Register for the
      years 2008-11. RESULTS: In the age group 6-12 years, nationwide prevalence
      amounted to 0.6% for autism spectrum disorders, 2.0% for ADHD, 0.9% for epilepsy
      and 0.3% for cerebral palsy. In total, 5.0% of all twelve-year-olds were
      registered with one or more of these diagnoses. The prevalence of autism spectrum
      disorders and ADHD varied between the counties, from 0.3% to 1.5% for autism
      spectrum disorders and from 1.1% to 3.5% for ADHD. For epilepsy and cerebral
      palsy there was little variation between the counties. Diagnostics and treatment
      of these four conditions are spread over 29 somatic hospitals and 102 units for
      child and youth psychiatry. INTERPRETATION: The variations across counties in the
      prevalence of autism spectrum disorders and ADHD are most likely due to
      variations in diagnostic practices. We ask whether it is appropriate to spread
      the provision of treatment across such a high number of institutions.

PMID- 24084969
TI  - [Use of coercion in nursing homes after new legislation].
AB  - BACKGROUND: The use of coercion in nursing homes is common as well as
      challenging, but was not regulated by law until 2009. Two key conditions are that
      the patient must be without mental competence and that the coercive measures are
      in the patient's best interest. Inspection reports have revealed insufficient
      application of the law, and this is of concern to patients as well as healthcare
      staff. With the aid of a qualitative study, we wished to identify the challenges
      encountered and the experiences gained by doctors and other nursing-home
      personnel from the new provisions regarding the use of coercion. MATERIAL AND
      METHOD: A total of 65 nursing-home employees were interviewed in focus groups.
      The interview guide included questions on, for example, when coercion is being
      used and how the new chapter of the Act is being applied. In the qualitative
      analysis, the content of the statements was categorised and condensed. RESULTS:
      All focus-group interviews described coercion as frequently occurring, but also
      that few formal decisions are being made. Involvement of the doctors and inter
      disciplinary cooperation were assessed as crucial for ensuring appropriate
      application of the new regulations, in addition to time, staffing and competence.
      The participants were uncertain as to how the new regulations should be applied,
      and regarded the requirements for a formal decision as unrealistic. Some of the
      coercive measures described are illegal. The absence of legal authority in cases
      where coercion is regarded as the lesser evil was described as challenging.
      INTERPRETATION: The new legal basis for the use of coercion is likely to raise
      awareness of the issue, but has a large potential for erroneous interpretation
      and causing reluctance to make formal decisions. In some areas, the law is out of
      step with the realities in nursing homes and the employees' values.

PMID- 24084971
TI  - [Primary myelofibrosis--pathogenesis, diagnosis and treatment].
AB  - BACKGROUND: Primary myelofibrosis is a malignant myeloproliferative disease. It
      is characterised by proliferation of megakaryocytes in the bone marrow,
      dysregulated cytokine production and reactive fibrosis that causes bone marrow
      failure. The purpose of this article is to provide an up-to-date presentation of
      the pathophysiology, diagnostics and treatment of the disease. METHOD: The
      article is based on the authors' own experience and on a selection of articles
      identified through many years of experience of treating patients with
      myelofibrosis. RESULTS: The molecular mechanisms that trigger the disease remain
      unidentified, but mutations in two genes (JAK2 and MPL) occur in 70% of patients
      and result in increased production of haematopoietic cells. Diagnosis is based on
      clinical examination, bone marrow histology and molecular biological
      examinations. The clinical course of primary myelofibrosis varies. Life
      expectancy depends on a number of factors and is severely decreased by high-risk
      disease. Allogeneic stem cell transplantation is the only treatment with a
      curative potential, but only a minority of patients are eligible for it. If
      transplantation is not possible, therapy is symptomatic. JAK2-inhibitors are new
      drugs that counteract cytokine production and cell proliferation. Ruxolitinib is
      the first approved JAK2 inhibitor and has proved effective on symptoms and
      quality of life. INTERPRETATION: Medical inhibition of the JAK2 gene and
      associated JAK-STAT signalling pathway is a step forward in treatment. However,
      stem cell transplantation remains the only potentially curative treatment for
      myelofibrosis.

PMID- 24084970
TI  - New oral anticoagulants--a review.
AB  - BACKGROUND: Dabigatran, rivaroxaban and apixaban are three new oral
      anticoagulants that have recently been approved in Norway. The aim of this
      article is to provide an overview of the mechanisms of action, the most important
      indications and practical advice on the use of these drugs. METHOD: The review is
      based on published phase 3 studies, a literature search in PubMed and the
      authors' clinical experience. RESULTS: Indications for use of the new
      anticoagulants include thromboprophylaxis after total hip and knee replacement
      surgery (all three), prevention of stroke and systemic embolism in non-valvular
      atrial fibrillation (all three), treatment of acute venous thrombosis and
      secondary prophylaxis after venous thrombosis (currently only rivaroxaban). For
      the aforementioned indications, these drugs have proven to be non-inferior to
      standard established anticoagulation therapy. For atrial fibrillation, all three
      drugs have also shown a lower incidence of intracranial bleeding compared with
      standard treatment. INTERPRETATION: It is important to limit the use of these
      drugs to approved indications, to select patients who show good compliance, to
      rule out contraindications and to identify drug interactions. Monitoring of
      coagulation is not required, but patients should be followed up regularly to
      detect conditions that may lead to changes in the expected efficacy or safety.

PMID- 24084972
TI  - [When the numbers need treatment].

PMID- 24084973
TI  - [Patient autonomy is not an easy matter].

PMID- 24084974
TI  - ["Blood-thinning medicine"].

PMID- 24084979
TI  - Phytotoxicities of inorganic arsenic and dimethylarsinic acid to Arabidopsis
      thaliana and Pteris vittata.
AB  - The mechanisms by which Pteris vittata (L.) hyperaccumulates arsenic (As) have
      not been fully elucidated. To investigate how P. vittata tolerates high
      concentrations of arsenite, we compared the toxicities of various As compounds to
      P. vittata and Arabidopsis thaliana (L.). The phytotoxicities of As species were
      found to be in the order of arsenite > arsenate > dimethylarsinic acid (DMAA) in
      A. thaliana, and in the order of DMAA > arsenate > arsenite in P. vittata. P.
      vittata calli displayed a weaker ability to absorb arsenite than arsenate. These
      results demonstrate that P. vittata possesses mechanisms of As accumulation and
      detoxification. 

PMID- 24084980
TI  - Determination of mercury in some freshwater fish species from Chahrmahal va
      Bakhtyari Province, Iran and potential limits for human consumption.
AB  - Concentrations of mercury in four freshwater fish species from Gandoman and
      Sooleghan Lagoons and Beheshtabad River were determined by cold vapor atomic
      absorption spectrometry. Concentrations of mercury in muscle of 90 fish ranged
      from 21 to 31 MUg kg(-1) (mean = 26 MUg kg(-1)). Statistical analysis showed no
      statistical relationship between mean mercury concentration and fish species,
      although concentration of mercury in different seasons and habitats was
      statistically different (p < 0.05). The results indicated that fish from Gandoman
      and Sooleghan Lagoons and Beheshtabad River have concentrations well below the
      maximum permissible levels of mercury according to international standards with
      no health risk for consumers.

PMID- 24084981
TI  - Interleukin-24 inhibits cell migration and invasion in the neuroblastoma cell
      line SH-SY5Y.
AB  - Neuroblastomas are common pediatric solid tumors with a variable clinical course;
      approximately 50% of patients present with metastatic disease at diagnosis. The
      development of metastatic lesions often causes a fatal outcome. Therefore, the
      prevention of metastases during the early stage of tumor development is critical
      for the improvement of the prognosis of neuroblastoma patients. We previously
      observed the suppression of neuroblastoma growth in response to overexpression of
      interleukin-24 (IL-24) in vitro and in vivo. IL-24 exerts its tumor-suppressive
      effects by multiple mechanisms, including the balance of Bcl-2 family proteins
      toward the pro-apoptotic pathway and the activation of the caspase cascade. In
      this study, we used adenovirus-mediated IL-24 (Ad-IL24) to examine the effect of
      the ectopic production of IL-24 on cell migration and invasion in human
      neuroblastoma cells. We found that IL-24 effectively inhibits SH-SY5Y
      neuroblastoma cell migration and invasion by changing subcellular localization
      and cellular levels of beta-catenin and regulating the levels of proteins
      associated with cell migration and invasion. Thus, IL-24 should be considered a
      therapeutic agent that can inhibit primary neuroblastoma growth and that may
      prevent metastasis.

PMID- 24084982
TI  - Functional salivary gland regeneration by transplantation of a bioengineered
      organ germ.
AB  - Salivary gland hypofunction, also known as xerostomia, occurs as a result of
      radiation therapy for head cancer, Sjogren's syndrome or aging, and can cause a
      variety of critical oral health issues, including dental decay, bacterial
      infection, mastication dysfunction, swallowing dysfunction and reduced quality of
      life. Here we demonstrate the full functional regeneration of a salivary gland
      that reproduces the morphogenesis induced by reciprocal epithelial and
      mesenchymal interactions through the orthotopic transplantation of a
      bioengineered salivary gland germ as a regenerative organ replacement therapy.
      The bioengineered germ develops into a mature gland through acinar formations
      with a myoepithelium and innervation. The bioengineered submandibular gland
      produces saliva in response to the administration of pilocarpine and gustatory
      stimulation by citrate, protects against oral bacterial infection and restores
      normal swallowing in a salivary gland-defective mouse model. This study thus
      provides a proof-of-concept for bioengineered salivary gland regeneration as a
      potential treatment of xerostomia. 

PMID- 24084983
TI  - Magneto-dielectric effects induced by optically-generated intermolecular charge
      transfer states in organic semiconducting materials.
AB  - Traditionally, magneto-dielectric effects have been developed by combining
      ferroelectric and magnetic materials. Here, we show a magneto-dielectric effect
      from optically-generated intermolecular charge-transfer states in an organic
      semiconducting donor:acceptor (PVK:TCNB) system. We observe in magnetic field
      effects of photoluminescence that a magnetic field can change singlet/triplet
      population ratio in intermolecular charge-transfer states. Furthermore, our
      theoretical analysis and experimental evidence indicate that the singlets and
      triplets in charge-transfer states have stronger and weaker electrical
      polarizations, respectively. Therefore, the observed magneto-dielectric effect
      can be attributed to magnetically-dependent singlet/triplet ratio in
      intermolecular charge-transfer states. In principle, a magneto-dielectric effect
      can be generated through two different channels based on magneto-polarization and
      magneto-current effects when the singlet/triplet ratio in intermolecular charge
      transfer states is changed by a magnetic field. We find, from the simulation of
      dielectric effects, that magneto-polarization and magneto-current effects play
      primary and secondary roles in the generation of magneto-dielectric effect. 

PMID- 24084985
TI  - A two-directional approach to pyrrolizidines: total syntheses and biological
      evaluation of alkaloid cis-223B and (+/-)-xenovenine.
AB  - Total syntheses of alkaloid cis-223B and xenovenine are reported in 3 and 4 steps
      respectively using a two-directional synthesis/triple reductive amination
      strategy, and their neurotoxic properties assessed. 

PMID- 24084984
TI  - Network analysis of differential Ras isoform mutation effects on intestinal
      epithelial responses to TNF-alpha.
AB  - Tumor necrosis factor alpha (TNF-alpha) is an inflammatory cytokine that can
      elicit distinct cellular behaviors under different molecular contexts. Mitogen
      activated protein kinase (MAPK) pathways, especially the extracellular signal
      regulated kinase (Erk) pathway, help to integrate influences from the
      environmental context, and therefore modulate the phenotypic effect of TNF-alpha
      exposure. To test how variations in flux through the Erk pathway modulate TNF
      alpha-elicited phenotypes in a complex physiological environment, we exposed mice
      with different Ras mutations (K-Ras activation, N-Ras activation, and N-Ras
      ablation) to TNF-alpha and observed phenotypic and signaling changes in the
      intestinal epithelium. Hyperactivation of Mek1, an Erk kinase, was observed in
      the intestine of mice with K-Ras activation and, surprisingly, in N-Ras null
      mice. Nevertheless, these similar Mek1 outputs did not give rise to the same
      phenotype, as N-Ras null intestine was hypersensitive to TNF-alpha-induced
      intestinal cell death while K-Ras mutant intestine was not. A systems biology
      approach applied to sample the network state revealed that the signaling contexts
      presented by these two Ras isoform mutations were different. Consistent with our
      experimental data, N-Ras ablation induced a signaling network state that was
      mathematically predicted to be pro-death, while K-Ras activation did not. Further
      modeling by constrained Fuzzy Logic (cFL) revealed that N-Ras and K-Ras activate
      the signaling network with different downstream distributions and dynamics, with
      N-Ras effects being more transient and diverted more towards PI3K-Akt signaling
      and K-Ras effects being more sustained and broadly activating many pathways. Our
      study highlights the necessity to consider both environmental and genomic
      contexts of signaling pathway activation in dictating phenotypic responses, and
      demonstrates how modeling can provide insight into complex in vivo biological
      mechanisms, such as the complex interplay between K-Ras and N-Ras in their
      downstream effects. 

PMID- 24084986
TI  - Angular distribution of diffuse reflectance from incoherent multiple scattering
      in turbid media.
AB  - The angular distribution of diffuse reflection is elucidated with greater
      understanding by studying a homogeneous turbid medium. We modeled the medium as
      an infinite slab and studied the reflection dependence on the following three
      parameters: the incident direction, optical depth, and asymmetry factor. The
      diffuse reflection is produced by incoherent multiple scattering and is solved
      through radiative transfer theory. At large optical depths, the angular
      distribution of the diffuse reflection with small incident angles is similar to
      that of a Lambertian surface, but, with incident angles larger than 60 degrees ,
      the angular distributions have a prominent reflection peak around the specular
      reflection angle. These reflection peaks are found originating from the
      scattering within one transport mean free path in the top layer of the medium.
      The maximum reflection angles for different incident angles are analyzed and can
      characterize the structure of angular distributions for different asymmetry
      factors and optical depths. The properties of the angular distribution can be
      applied to more complex systems for a better understanding of diffuse reflection.

PMID- 24084987
TI  - Target-oriented design method for ultrabroadband single-mode triple-clad fibers.
AB  - Many inherent troubles from holey fiber technology are avoided according to
      leakage losses from the endlessly single-mode (ESM) property. The target-oriented
      design method (TODM) brings the potentialities of triple-clad fibers (TCFs) with
      arbitrarily available structure and performance into full play in transmission
      performance, because of the scalar wave equation combined with infinitesimal
      calculus of fiber performance. TCF with modified total internal reflection
      guidance optimized by TODM under the tolerance Deltah<sub>1</sub><=6% has an
      ultrabroadband single-mode property similar to the ESM property of solid-core
      microstructured nonzero dispersion shifted fibers without tolerance and optimal
      structure to avoid higher-order modes and to reduce macro-bending loss. 

PMID- 24084988
TI  - Optimal design of optical system for LED road lighting with high illuminance and
      luminance uniformity.
AB  - A new method is proposed to achieve high illuminance and luminance uniformity of
      the road surface in LED road lighting. Based on the reflection properties of the
      road surface, the illuminance and luminance are analyzed simultaneously with the
      least-square method; meanwhile, energy efficiency and glare requirements are
      considered. Through the analysis and calculations, the optimal light distribution
      of a luminaire is obtained, and then a freeform lens with this light distribution
      is designed. For a 2-lane C1 class road illuminated by LED luminaires mounted
      with these lenses, the overall illuminance and luminance uniformity on the road
      surface can reach over 0.9 and 0.85, respectively, and the glare factors less
      than 10%. 

PMID- 24084989
TI  - Synchronized Fabry-Perot cavity used for enhanced sensitivity electro-optic
      measurements of electric fields in the microwave range.
AB  - An electro-optic (EO) sensing system for measuring free-space electric fields in
      the microwave range has been developed. The system is based on a phase modulation
      heterodyning technique using a Mach-Zehnder interferometer. In one of the arms of
      the interferometer, an acousto-optic frequency shifter is used to downconvert the
      frequency of the detected signal in order to discriminate it from parasites
      emitted at the external electric field frequency. The sensing part is a
      LiTaO<sub>3</sub> crystal placed in a Fabry-Perot cavity. The cavity aims at
      enhancing the sensitivity of the measurements. Cavity-based EO setups already
      used in the literature propose this sensitivity enhancement at the expense of the
      frequency bandwidth, whereas our setup allows this without a major impact on the
      frequency bandwidth. Electric fields are measured at both 15 kHz and 2.4 GHz with
      cavities of two different finesses; the best EO phase retardation gains obtained
      with the cavity are 34 and 60, respectively. The minimum detectable electric
      field is 0.003  V?m<sup>-1</sup>?Hz<sup>-1/2</sup>.

PMID- 24084990
TI  - Performance evaluation of receive-diversity free-space optical communications
      over correlated Gamma-Gamma fading channels.
AB  - The efficacy of spatial diversity in practical free-space optical communication
      systems is impaired by the fading correlation among the underlying subchannels.
      We consider in this paper the generation of correlated Gamma-Gamma random
      variables in view of evaluating the system outage probability and bit-error-rate
      under the condition of correlated fading. Considering the case of receive
      diversity systems with intensity modulation and direct detection, we propose a
      set of criteria for setting the correlation coefficients on the small- and large
      scale fading components based on scintillation theory. We verify these criteria
      using wave-optics simulations and further show through Monte Carlo simulations
      that we can effectively neglect the correlation corresponding to the small-scale
      turbulence in most practical systems, irrespective of the specific turbulence
      conditions. This has not been clarified before, to the best of our knowledge. We
      then present some numerical results to illustrate the effect of fading
      correlation on the system performance. Our conclusions can be generalized to the
      cases of multiple-beam and multiple-beam multiple-aperture systems. 

PMID- 24084992
TI  - Experimental study on the all-fiberized continuous-wave ytterbium-doped laser
      operating near 980 nm.
AB  - All-fiberized continuous-wave Yb-doped fiber lasers operating near 980 nm are
      fabricated, and 1.73 W, 980 nm lasing is obtained. Moreover, the output
      properties of the 980 nm fiber laser are studied by experiment. It is
      demonstrated, for the first time to the best of our knowledge, that the output
      power curve versus the active fiber length experiences double-peak values, which
      are caused by the red shift of the lasing wavelength induced by the longitudinal
      mode competition. It is also demonstrated that the pump threshold increases
      exponentially with the active fiber length. The relationship between the pump
      threshold and the optimum active fiber length is examined.

PMID- 24084991
TI  - Two regimes of wide angle acousto-optic interaction in tellurium dioxide single
      crystals.
AB  - The paper presents results of investigation of wide angle acousto-optic (AO)
      diffraction based on light beams propagating in birefringent crystals far away
      from optical axes and also close to the optical axes. A comparison of the two
      cases of wide angle interaction in tellurium dioxide crystal is carried out.
      Advantages and drawbacks of the far-off axis (FOA) diffraction are examined in
      the paper. Possibility of application of the FOA diffraction in imaging AO
      filters is discussed. Results of theoretical consideration of the problem are
      experimentally confirmed in a paratellurite filter using a slow shear acoustic
      wave propagating in the (11-0) plane of the crystal at the angle alpha=10 degrees
      relative to the axis [110]. 

PMID- 24084993
TI  - Application of the random ball test for calibrating slope-dependent errors in
      profilometry measurements.
AB  - Optical profilometers such as scanning white light interferometers and confocal
      microscopes provide high-resolution measurements and are widely utilized in many
      fields for measuring surface topography. Slope-dependent systematic errors can be
      present in the measurement and can be the same order of magnitude as features on
      the surface to be measured. We propose a self-calibration technique, the random
      ball test (RBT), for calibrating slope-dependent errors of such instruments. The
      calibration result can be used to compensate future measurements of similar
      spherical geometries such as profiles of refractive microlenses. A simulation
      study validates the approach and shows that the RBT is effective in practical
      limits. We demonstrate the calibration on a 50* confocal microscope and find a
      surface slope-dependent bias that increases monotonically with the magnitude of
      the surface slope and is as large as ~800  nm at a surface slope of 12 degrees .
      The uncertainty of the calibration is smaller than the observed measurement bias
      and is dominated by residual random noise. Effects such as drift and ball radius
      uncertainty were investigated to understand their contribution to the calibration
      uncertainty.

PMID- 24084994
TI  - Characterization and correction of spherical aberration due to glass substrate in
      the design and fabrication of Fresnel zone lenses.
AB  - As with a conventional lens, a Fresnel zone lens (FZL) can be used to image
      objects at infinity or nearby. In the latter case, the FZL converts a diverging
      spherical wavefront into a converging spherical wavefront. The glass substrate on
      which the FZL is fabricated introduces spherical aberration resulting in a shift
      of the image plane and blurring of the image. Two novel schemes for correction of
      this spherical aberration are proposed and studied in this paper. To demonstrate
      them, FZLs are designed with and without aberration correction. They are
      fabricated using electron beam direct writing. The devices are evaluated and the
      accuracy of the proposed aberration correction schemes is validated. 

PMID- 24084995
TI  - Design of a silicon Mach-Zehnder modulator with a U-type PN junction.
AB  - We have developed a silicon depletion-mode modulator featuring a novel U-type PN
      junction that enables a substantial improvement in electro-optical modulation
      efficiency. Through electrical, optical, and manufacturing process simulations,
      an ultralow V<sub>pi</sub>L of 0.63  V.cm is exhibited with 3 V reverse bias. The
      high modulation efficiency enables a high extinction ratio (ER) of >17  dB with
      only a 1 mm phase shifter when the excess loss at the "on" state is 2 dB. The ER
      can maintain >12  dB at ~28  GHz operation with a 3 V peak-to-peak voltage due to
      the small voltage attenuation of the short phase shifter.

PMID- 24084996
TI  - Iridium-coated micropore x-ray optics using dry etching of a silicon wafer and
      atomic layer deposition.
AB  - To enhance x-ray reflectivity of silicon micropore optics using dry etching of
      silicon (111) wafers, iridium coating is tested by use of atomic layer
      deposition. An iridium layer is successfully formed on sidewalls of tiny
      micropores with a pore width of 20 MUm and depth of 300 MUm. The film thickness
      is ~20  nm. An enhanced x-ray reflectivity compared to that of silicon is
      confirmed at Ti K<sub>alpha</sub> 4.51 keV, for what we believe to be the first
      time, with this type of optics. Some discrepancies from a theoretical
      reflectivity curve of iridium-coated silicon are noticed at small incident angles
      <1.3 degrees . When a geometrical shadowing effect due to occultation by a ridge
      existing on the sidewalls is taken into account, the observed reflectivity
      becomes well represented by the modified theoretical curve. An estimated surface
      micro roughness of ~1  nm rms is consistent with atomic force microscope
      measurements of the sidewalls.

PMID- 24084997
TI  - Vibration insensitive extended range interference microscopy.
AB  - Using a simultaneous phase sensor, the proposed instrument performs highly
      repeatable measurements over an extended range in the presence of vibration
      common to a laboratory setting. Measurement of a 4.5 MUm step standard in the
      presence of vibration amplitudes of 40 nm produces a repeatability of 1.5 nm RMS
      with vertical scanning data acquired at 400 nm intervals. The outlined method
      demonstrates the potential to tolerate larger vibration amplitudes up to or
      beyond a quarter wavelength and to increase the data acquisition step size to
      that approaching the depth of field of standard microscope imaging systems.

PMID- 24084998
TI  - Study of Zernike polynomials of an elliptical aperture obscured with an
      elliptical obscuration: comment.
AB  - Recently, Hasan and Shaker published a set of orthonormal polynomials for an
      annular elliptical pupil obtained by the Gram-Schmidt orthogonalization of the
      Zernike circle polynomials [Appl. Opt.51, 8490 (2012)]. However, the expressions
      for many of the polynomials are incorrect, apparently due to wrong usage of the
      Gram-Schmidt orthogonalization process. We provide the correct equations for the
      orthogonalization process and the expressions for the orthonormal polynomials
      obtained by applying them. 

PMID- 24084999
TI  - Study of Zernike polynomials of an elliptical aperture obscured with an
      elliptical obscuration: reply.
AB  - In our previous paper [Appl. Opt.51, 8490 (2012)] we considered the Zernike
      polynomials for a unit annular ellipse aperture. In that paper many equations
      were used and were solved by MATLAB language and by hand, and many times these
      rewritten equations had some written mistakes. In the Diaz and Mahajan comment
      [Appl. Opt.52, 5962 (2013)] on the work, some remarks were true and others were
      not. In this reply, we will discuss their comment in detail. 

PMID- 24085000
TI  - Reducing temperature dependence of the output energy of a quasi-continuous wave
      diode-pumped Nd:YAG laser.
AB  - It is demonstrated by numerical modeling that spectrally dispersed compound
      pumping diodes and low-loss pumping chamber reduced the temperature dependence of
      the output energy of quasi-continuous wave diode-pumped Nd:YAG lasers
      considerably. Several compound diodes with different spectral profiles were
      tested for pumping. The laser energy was calculated as a function of diode
      temperature from -30 degrees C to 60 degrees C. When a compound diode with a flat
      top spectrum was used for pumping, the mean laser energy was 83% of the maximum
      energy of a Nd:YAG laser pumped by a diode with a narrow bandwidth. In addition,
      a compound diode with three emission lines was tested for pumping. When the
      wavelength gap between the adjacent emission lines of the pumping diode was in
      the range of 3-10 nm, the mean energy of the Nd:YAG laser became similar to that
      of a Nd:YAG laser pumped by a diode with a flat-top spectrum.

PMID- 24085001
TI  - Simple and rapid data-reduction method with pixel-level spatial frequency of
      shift-rotation method.
AB  - Absolute testing methods are commonly employed in surface metrology to calibrate
      the reference surface deviation and obtain the absolute deviation of the surface
      under test. A simple and reliable data-reduction method of absolute shift
      rotation method with rotational and translational measurements is presented here,
      which relies on the decomposition of the surface deviation into rotationally
      asymmetric and symmetric components. The rotationally asymmetric surface
      deviation can be simply obtained by classical N-position averaging method. After
      that, the two-dimensional problem of estimating the other rotationally symmetric
      surface deviation can be simplified to a one-dimensional problem, and it can be
      directly calculated out with pixel-level spatial frequency based on several
      measurements of different translations in one same direction. Since that no
      orthogonal polynomials fitting, such as Zernike polynomials, is required in the
      calculation, the data reduction of the method is simple and rapid. Experimental
      absolute results of spherical surfaces are given. 

PMID- 24085002
TI  - Laser beam diffraction at the edge of a film and application to thin film
      metrology.
AB  - The thickness change of a film is measured optically using self-interference of a
      single laser beam incident at the edge of the film. Theory suggests that when a
      half-plane phase shift is applied to a Gaussian laser beam, interference fringes
      appear in the near and far field, in which position varies with the amount of
      phase shift. By measuring fringe pattern displacement, we demonstrate detection
      of thickness changes in chitosan films induced by temperature rises of a few
      degrees centigrade. With a laser at 543 nm, the minimum detectable thickness
      change is 0.8 nm in ideal conditions (quarter wave films), corresponding with a
      phase shift of 0.02 rad, and the minimum detectable film thickness is ~30  nm.
      Potential use for surface temperature measurements is discussed.

PMID- 24085003
TI  - Time-domain geometrical localization of point-like fluorescence inclusions in
      turbid media with early photon arrival times.
AB  - We introduce a novel approach for localizing a plurality of discrete point-like
      fluorescent inclusions embedded in a thick turbid medium using time-domain
      measurements. The approach uses early photon information contained in measured
      time-of-flight distributions originating from fluorescence emission. Fluorescence
      time point-spread functions (FTPSFs) are acquired with ultrafast time-correlated
      single photon counting after short pulse laser excitation. Early photon arrival
      times are extracted from the FTPSFs obtained from several source-detector
      positions. Each source-detector measurement allows defining a geometrical locus
      where an inclusion is to be found. These loci take the form of ovals in 2D or
      ovoids in 3D. From these loci a map can be built, with the maxima thereof
      corresponding to positions of inclusions. This geometrical approach is supported
      by Monte Carlo simulations performed for biological tissue-like media with
      embedded fluorescent inclusions. To validate the approach, several experiments
      are conducted with a homogeneous phantom mimicking tissue optical properties. In
      the experiments, inclusions filled with indocyanine green are embedded in the
      phantom and the fluorescence response to a short pulse of excitation laser is
      recorded. With our approach, several inclusions can be localized with low
      millimeter positional error. Our results support the approach as an accurate,
      efficient, and fast method for localizing fluorescent inclusions embedded in
      highly turbid media mimicking biological tissues. Further Monte Carlo simulations
      on a realistic mouse model show the feasibility of the technique for small animal
      imaging. 

PMID- 24085004
TI  - Intensity profile of light scattered from a rough surface.
AB  - We present in this paper, approximate analytical expressions for the intensity of
      light scattered by a rough surface, whose elevation xi(x,y) in the z-direction is
      a zero mean stationary Gaussian random variable. With (x,y) and
      (x<sup>'</sup>,y<sup>'</sup>) being two points on the surface, we have
      <xi(x,y)>=0 with a correlation,
      <xi(x,y)xi(x<sup>'</sup>,y<sup>'</sup>)>=sigma<sup>2</sup>g(r), where r=[(x
      x<sup>'</sup>)<sup>2</sup>+(y-y<sup>'</sup>)<sup>2</sup>]<sup>1/2</sup> is the
      distance between these two points. We consider g(r)=exp[-(r/l)<sup>beta</sup>]
      with 1<=beta<=2, showing that g(0)=1 and g(r)->0 for r?l. The intensity
      expression is sought to be expressed as
      f(v<sub>xy</sub>)={1+(c/2y)[vx2+vy2]}<sup>-y</sup>, where v<sub>x</sub> and
      v<sub>y</sub> are the wave vectors of scattering, as defined by the Beckmann
      notation. In the paper, we present expressions for c and y, in terms of sigma, l,
      and beta. The closed form expressions are verified to be true, for the cases
      beta=1 and beta=2, for which exact expressions are known. For other cases, i.e.,
      beta?1, 2 we present approximate expressions for the scattered intensity, in the
      range, v<sub>xy</sub>=(vx2+vy2)<sup>1/2</sup><=6.0 and show that the relation for
      f(v<sub>xy</sub>), given above, expresses the scattered intensity quite
      accurately, thus providing a simple computational methods in situations of
      practical importance. 

PMID- 24085005
TI  - Three-dimensional display based on dual parallax barriers with uniform
      resolution.
AB  - The 3D display based on a parallax barrier is a low-cost autostereoscopic
      display. However, the vertical and horizontal resolution of the 3D images
      displayed on it will be seriously nonuniform as this display has a large number
      of views. It will worsen the display quality; therefore, a 3D display that
      consists of a 2D display panel and dual parallax barriers is proposed. With a 2D
      display panel, the proposed 3D display provides the synthetic images with square
      pixel units in which the arrangement of pixels can make the 3D image have uniform
      resolution. With the dual parallax barriers, the proposed 3D display shows the
      pixels in square pixel units for different horizontal views. Therefore, this
      display has uniform resolution of 3D images. A four-view prototype of the
      proposed 3D display is developed, and it provides uniform 3D resolution in the
      vertical and horizontal directions. 

PMID- 24085006
TI  - Framework for gradient integration by combining radial basis functions method and
      least-squares method.
AB  - A framework with a combination of the radial basis functions (RBFs) method and
      the least-squares integration method is proposed to improve the integration
      process from gradient to shape. The principle of the framework is described, and
      the performance of the proposed method is investigated by simulation. Improvement
      in accuracy is verified by comparing the result with the usual RBFs-based subset
      by-subset stitching method. The proposed method is accurate, automatic, easily
      implemented, and robust and even works with incomplete data. 

PMID- 24085007
TI  - Simulation and measurement of optical aberrations of injection molded progressive
      addition lenses.
AB  - Injection molding is an important mass-production tool in the optical industry.
      In this research our aim is to develop a process of combining ultraprecision
      diamond turning and injection molding to create a unique low-cost manufacturing
      process for progressive addition lenses (PALs). In industry, it is a well-known
      fact that refractive index variation and geometric deformation of injection
      molded lenses due to the rheological properties of polymers will distort their
      optical performance. To address this problem, we developed a method for
      determining the optical aberrations of the injection molded PALs. This method
      involves reconstructing the wavefront pattern in the presence of uneven
      refractive index distribution and surface warpage using a finite element method.
      In addition to numerical modeling, a measurement system based on a Shack-Hartmann
      wavefront sensor was used to verify the modeling results. The measured
      spherocylindrical powers and aberrations of the PALs were in good agreement with
      the model. Consequently, the optical aberrations of injection molded PALs were
      successfully predicted by finite element modeling. In summary, it was
      demonstrated in this study that numerically based optimization for PAL
      manufacturing is feasible. 

PMID- 24085008
TI  - Modeling of the general astigmatic Gaussian beam and its propagation through 3D
      optical systems.
AB  - The paper introduces the complete model of the general astigmatic Gaussian beam
      as the most general case of the Gaussian beam in the fundamental mode. This
      includes the laws of propagation, reflection, and refraction as well as the
      equations for extracting from the complex-valued beam description its real-valued
      parameters, such as the beam spot radii and the radii of curvature of the
      wavefront. The suggested model is applicable to the case of an oblique incidence
      of the beam at any 3D surface that can be approximated by the second-order
      equation at the point of incidence. Thus it can be used in simulations of a large
      variety of 3D optical systems. The provided experimental validation of the model
      shows good agreement with simulations. 

PMID- 24085009
TI  - Plasmonic "pump-probe" method to study semi-transparent nanofluids.
AB  - Nanofluids have been increasingly used in a wide range of thermal applications.
      Although these applications can benefit greatly from investigating the behavior
      of nanoparticles under different heating scenarios, there is a lack of
      experiments that can achieve this. To overcome this challenge, an optical "pump
      probe"-type experiment is suggested in this paper. In experiments of this type, a
      set of "pumping" nanoparticles are specifically selected to absorb laser
      radiation. These particles represent a flexible tool for volumetric heating. A
      second set of "probing" nanoparticles can be tailored to scatter a separate
      optical probing signal. This work presents a selection procedure for
      nanoparticles of both types. The selection procedure is then demonstrated for a
      specific example where the pump and probe wavelengths are of 980 and 532 nm,
      respectively. Gold nanorods with diameters of 10 and a length of 58 nm are
      selected as the "most suitable" absorbing particles, while silver nanospheres
      with a diameter of 110 nm are selected as the "most suitable" scattering
      particles. These particles are synthesized and shown to experimentally match the
      desired optical properties. Overall, this paper proposes and demonstrates an
      approach by which it is possible to design and fabricate particles for a wide
      range of optical studies in semi-transparent nanofluids. 

PMID- 24085010
TI  - Comprehensive polarimetric analysis of Spectralon white reflectance standard in a
      wide visible range.
AB  - Since polarimetry has extended its use for the study of scattering from surfaces
      and tissues, Spectralon, a white reflectance standard, is acquiring the role of a
      polarimetric standard. Both the behavior of Spectralon as a Lambertian surface
      and its performance as a perfect depolarizer are analyzed in detail. The accuracy
      of our dynamic polarimeter, together with the polar decomposition to describe the
      Mueller matrix (MM) depolarizing action, combine to produce a powerful tool for
      the proper analysis of this scattering surface. Results allowed us to revisit,
      for confirmation or revision, the role of some MM elements, as described in the
      bibliography. The conditions under which it can be considered a good Lambertian
      surface are specified in terms of incidence and scattering angle and verified
      over a large wavelength range. 

PMID- 24085011
TI  - MATISSE-v2.0 infrared sea images: sensitivity analysis and experimental
      validation using MIRAMER campaign measurements in solar glint configurations.
AB  - The validation of the multiresolution model of sea radiance in the infrared,
      developed at Onera, is investigated by comparison with measurements obtained
      during the MIRAMER campaign that took place in May 2008 in the Mediterranean Sea.
      The sea radiance model and optical properties are expressed and the experimental
      setup of the campaign is briefly presented. We focus on solar glint measurements
      collected on the 22nd of May at 5 h 59 m 50 s in the mid-wave IR (3.93-4.14 MUm)
      band and the long-wave IR (8.19-8.96 MUm) band onboard the research vessel (R/V)
      Atalante at a grazing observational angle. A sensitivity analysis of glitter
      radiance on atmospheric and aerosol profiles, as well as sea temperature and wind
      speed in the vicinity of the measured contextual parameters, is presented.
      Modeled and measured images are compared and results are delved into further by
      comparisons of histograms, averaged vertical and horizontal profiles. Errors in
      the 3.93-4.14 MUm band are under those potentially due to calibration, whereas
      discrepancies are noticed in the 8.19-8.96 MUm band, where the deepest analysis
      has to be performed.

PMID- 24085012
TI  - Selective reflection technique as a probe to monitor the growth of metallic thin
      film on dielectric surfaces.
AB  - Controlling thin film formation is technologically challenging. The knowledge of
      physical properties of the film and of the atoms in the surface vicinity can help
      improve control over the film growth. We investigate the use of the well
      established selective reflection technique to probe the thin film during its
      growth, simultaneously monitoring the film thickness, the atom-surface van der
      Waals interaction, and the vapor properties in the surface vicinity. 

PMID- 24085013
TI  - Demonstration of a multichannel, multiresolution imaging system.
AB  - In conventional multichannel imaging systems, all channels have similar imaging
      properties [field-of-view (FOV) and angular resolution]. In our approach,
      channels are designed to have different imaging properties which add
      multiresolution capability to the system. We have experimentally demonstrated,
      for the first time to our knowledge, a three-channel imaging system which
      simultaneously captures multiple images having different magnifications and FOVs
      on an image sensor. Each channel consists of four aspherical lens surfaces
      fabricated from four PMMA plates by ultraprecision diamond tooling and of a
      baffle made from a titanium (Ti) and aluminum (Al) based metal alloy. The
      integrated imaging system is able to record a FOV of 7.6 degrees  with the first
      channel and 73 degrees  with the third channel while having a magnification ratio
      of about 6 between them. The experimental and simulation results, specifically
      the FOV and magnification ratios, are comparable, and this paves a way for low
      cost, compact imaging systems which can embed smart imaging functionalities. 

PMID- 24085014
TI  - Light extraction--a practical consideration for a plasmonic nano-ring laser.
AB  - An integrated semiconductor plasmonic nano-ring laser with a connecting output
      plasmonic waveguide for light extraction is proposed, designed and demonstrated
      numerically. The maximum light extraction efficiency can be up to 56%. The design
      was optimized with 2D FDTD and verified with 3D FDTD methods, where close
      agreement is shown between the two. 

PMID- 24085018
TI  - Re-visiting visiting hours.

PMID- 24085019
TI  - Evidence basis for anticoagulants for cerebral sinus venous thrombosis? Reply by
      David K. Cundiff.

PMID- 24085020
TI  - Impact of chronic kidney disease on carotid atherosclerosis according to blood
      pressure category: the Suita study.
AB  - BACKGROUND AND PURPOSE: We aimed to clarify the association of chronic kidney
      disease (CKD) with carotid atherosclerosis and the impact of CKD on carotid
      atherosclerosis according to blood pressure categories in an urban general
      population. METHODS: We studied 3466 Japanese individuals (35-93 years old) in
      the Suita Study. Carotid atherosclerosis was expressed as the maximum carotid
      intima-media thickness and the presence of stenosis (>25%). The estimated
      glomerular filtration rate was calculated using the equations recommended by the
      Japanese Society of Nephrology. CKD was defined as estimated glomerular
      filtration rate <60 mL/min per 1.73 m2. Blood pressure categories were defined by
      the European Society of Hypertension and European Society of Cardiology 2007
      criteria. RESULTS: The multivariable-adjusted maximum carotid intima-media
      thickness and odds ratio for stenosis in subjects with estimated glomerular
      filtration rate<50 mL/min per 1.73 m2 were greater than those in subjects with
      estimated glomerular filtration rate>=90 mL/min per 1.73 m(2). When subjects were
      stratified according to blood pressure categories, the multivariable-adjusted
      maximum carotid intima-media thickness was significantly greater in CKD subjects
      than in non-CKD subjects only in subjects with hypertension. Similarly, the
      impact of CKD on stenosis was evident only in subjects with hypertension
      (multivariable-adjusted odds ratios for stenosis [95% confidence interval] were
      2.21 [1.53-3.19] in non-CKD/hypertension and 3.16 [2.05-4.88] in CKD/hypertension
      compared with non-CKD/optimal blood pressure). CONCLUSIONS: In a general
      population, the association of CKD with carotid atherosclerosis was modest, but
      CKD was independently associated with carotid atherosclerosis in subjects with
      hypertension.

PMID- 24085021
TI  - Twenty-year trends in long-term mortality risk in 17,149 survivors of ischemic
      stroke less than 55 years of age.
AB  - BACKGROUND AND PURPOSE: The purpose of the present study was to investigate the 4
      year mortality risk among patients<55 years with a first ischemic stroke during
      1987-2006. METHODS: A total of 17,149 cases (37.4% women) aged 18 to 54 years who
      survived>=28 days after a first ischemic stroke were identified in the Swedish
      Inpatient Register from 1987 to 2006. All patients were followed for 4 years or
      until death. The standardized mortality ratio was calculated by comparing the
      mortality rates with those of the general population of equivalent age, sex, and
      calendar year. RESULTS: During the period, there were 1265 deaths. Long-term
      survival improved over time in both men and women. Among men, the mortality risk
      decreased by 32% (hazard ratio=0.68 [95% confidence interval, 0.56-0.82]) from
      the first 5-year period to the last 5-year period (1987-1991 versus 2002-2006),
      and among women, the mortality risk decreased by 45% (0.55 [0.41-0.75]). Despite
      an overall decrease in mortality, the standardized mortality ratios for the last
      5-year period remained high: 5.88 (95% confidence interval, 5.10-6.71) for men
      and 5.91 (4.68-7.29) for women with an absolute excess risk of 1.60 and 0.97 per
      100 person-years, respectively, with nearly half of all deaths related to
      cardiovascular disease. CONCLUSIONS: During the 20-year period, 4-year mortality
      decreased by one third but was still 6-fold higher than that of the general
      population in the most recent period, emphasizing the importance of secondary
      prevention in young persons who have had a stroke.

PMID- 24085022
TI  - Letter by Rangaraju and Jadhav regarding article, "Predicting clinical outcomes
      after thrombolysis using the iScore: results from the Virtual International
      Stroke Trials Archive".

PMID- 24085023
TI  - Bloody migraine?

PMID- 24085024
TI  - Response to letter regarding article, "Predicting clinical outcomes after
      thrombolysis using the iScore: results from the Virtual International Stroke
      Trials Archive".

PMID- 24085027
TI  - Migraine and hemorrhagic stroke: a meta-analysis.
AB  - BACKGROUND AND PURPOSE: Several studies have assessed the possible increased risk
      of hemorrhagic stroke in migraineurs, drawing differing conclusions. No meta
      analysis on the topic has been published to date. METHODS: Multiple electronic
      databases (MEDLINE, EMBASE, Science Citation Index, and the Cochrane Library)
      were systematically searched up to March 2013 for studies dealing with migraine
      and hemorrhagic stroke. We selected case-control and cohort studies with a clear
      definition of the diagnostic criteria for migraine and hemorrhagic stroke, using
      an adjusted model or a matching procedure that could control for potential
      confounders, and reporting effect estimates with 95% confidence intervals (CIs)
      or enough data to allow calculation of those numbers. Adjusted odds ratios and
      hazard ratios were used to estimate effect size. RESULTS: Of 11 264 records, we
      identified 8 studies (4 case-control and 4 cohort studies) involving a total of
      1600 hemorrhagic strokes, which were included in the meta-analysis. The overall
      pooled adjusted effect estimate of hemorrhagic stroke in subjects with any
      migraine versus control subjects was 1.48 (95% CI, 1.16-1.88; P=0.002), with
      moderate statistical heterogeneity (I(2)=54.7%; P value for Q test=0.031). The
      risk of hemorrhagic stroke in subjects with migraine with aura (1.62; 95% CI,
      0.87-3.03; P=0.129) was not significant. Compared with control subjects, the risk
      of hemorrhagic stroke was greater in females with any migraine (1.55; 95% CI,
      1.16-2.07; P=0.003) and in female migraineurs aged less than 45 years (1.57; 95%
      CI, 1.10-2.24; P=0.012). CONCLUSIONS: Available studies suggest that subjects
      with migraine have an increased risk of hemorrhagic stroke. Further studies are
      needed to address the hemorrhagic stroke risk according to migraine type, age,
      sex, and hemorrhagic stroke type.

PMID- 24085028
TI  - Evidence basis for anticoagulants for cerebral sinus venous thrombosis? Reply to
      David K. Cundiff.

PMID- 24085025
TI  - Brain regulation of thrombosis and hemostasis: from theory to practice.

PMID- 24085029
TI  - A radical but flawed proposal: comments on Rehm et al. 'Defining substance use
      disorders: do we really need more than heavy use?'.

PMID- 24085030
TI  - Glycosylation changes in the salivary glycoproteins of alcohol-dependent
      patients: a pilot study.
AB  - AIM: Glycosylation of serum proteins is affected with prolonged heavy drinking,
      and carbohydrate deficient transferrin (CDT) is well established and highly
      specific biomarker of sustained alcohol consumption. However, total amount of
      sialic acid is not the only glycoepitope that may be altered as a result of the
      disease. This work is focused on glycan structures altered in salivary
      glycoproteins of alcoholics, indicating the most efficient carriers of such
      marker glycoepitopes. METHODS: Salivary glycoproteins of 31 alcohol-dependent
      patients and 21 healthy controls were studied by means of lectin ELISA and lectin
      blotting with the lectins specific for core and antennary fucose, alpha2,3-bound
      sialic acid as well as T and Tn antigens in O-glycans. RESULTS: In direct lectin
      ELISA, core fucosylation, alpha2,3 sialylation and expression of T-antigen were
      significantly lowered in the saliva of alcohol-dependent patients. In lectin
      blotting ten glycoprotein bands were analyzed. The profile of disease-related
      alterations was found to be complex, but all six lectins studied here were able
      to detect altered glycan structures. In some glycoproteins the tendency to
      correct the glycosylation profile was observed after 7 weeks of abstinence.
      CONCLUSION: Alterations in the glycosylation profiles in the salivary
      glycoproteins of alcohol-dependent people were found. Some of salivary
      glycoproteins, such as alpha-amylase, clusterin, haptoglobin, heavy and light
      chains of immunoglobulins, and transferrin, seem to be worthy of detailed
      glycosylation analysis in the detection of alcohol dependence. Further studies
      may allow one to estimate if such glycomarkers may also reflect the amount of
      alcohol intake or the duration of alcohol intake.

PMID- 24085031
TI  - Rescue of heart lipoprotein lipase-knockout mice confirms a role for triglyceride
      in optimal heart metabolism and function.
AB  - Hearts utilize fatty acids as a primary source of energy. The sources of those
      lipids include free fatty acids and lipoprotein triglycerides. Deletion of the
      primary triglyceride-hydrolyzing enzyme lipoprotein lipase (LPL) leads to cardiac
      dysfunction. Whether heart LPL-knockout (hLPL0) mice are compromised due a
      deficiency in energetic substrates is unknown. To test whether alternative
      sources of energy will prevent cardiac dysfunction in hLPL0 mice, two different
      models were used to supply nonlipid energy. 1) hLPL0 mice were crossed with mice
      transgenically expressing GLUT1 in cardiomyocytes to increase glucose uptake into
      the heart; this cross-corrected cardiac dysfunction, reduced cardiac hypertrophy,
      and increased myocardial ATP. 2) Mice were randomly assigned to a sedentary or
      training group (swimming) at 3 mo of age, which leads to increased skeletal
      muscle production of lactate. hLPL0 mice had greater expression of the lactate
      transporter monocarboxylate transporter-1 (MCT-1) and increased cardiac lactate
      uptake. Compared with hearts from sedentary hLPL0 mice, hearts from trained hLPL0
      mice had adaptive hypertrophy and improved cardiac function. We conclude that
      defective energy intake and not the reduced uptake of fat-soluble vitamins or
      cholesterol is responsible for cardiac dysfunction in hLPL0 mice. In addition,
      our studies suggest that adaptations in cardiac metabolism contribute to the
      beneficial effects of exercise on the myocardium of patients with heart failure. 

PMID- 24085032
TI  - Punicalagin, a polyphenol in pomegranate juice, downregulates p53 and attenuates
      hypoxia-induced apoptosis in cultured human placental syncytiotrophoblasts.
AB  - Oxidative stress is associated with placental dysfunction and suboptimal
      pregnancy outcomes. Therapeutic interventions to limit placental injury from
      oxidative stress are lacking. Punicalagin is an ellagitannin and a potent
      antioxidant in pomegranate juice. We showed that both pomegranate juice and
      punicalagin decrease oxidative stress and apoptosis in cultured
      syncytiotrophoblasts. p53 is involved in the oxidative stress-induced apoptosis
      in trophoblasts. We now test the hypothesis that punicalagin limits trophoblast
      injury in vitro by regulating the levels of p53. We examined the expression of
      p53, mouse double minute 2 homolog, p21, hypoxia-inducible factor (HIF) alpha,
      and selected members of the B cell lymphoma 2 (BCL2) family of proteins in
      cultured syncytiotrophoblasts exposed to <=1% oxygen in the absence or presence
      of punicalagin. We found that punicalagin attenuated hypoxia-induced apoptosis in
      syncytiotrophoblasts, as quantified by levels of cleaved poly-ADP ribose
      polymerase. This protective effect was in part mediated by reduced p53 activity
      shown by decreased expression of p21, lower HIF1alpha expression, and limited
      activity of caspases 9 and 3. There was no change in expression of proteins in
      the BCL2 family, which are also important in apoptosis. The data support a role
      for downregulation of p53 in the protection of human trophoblasts by punicalagin.

PMID- 24085033
TI  - Advancements and challenges in generating accurate animal models of gestational
      diabetes mellitus.
AB  - The maintenance of glucose homeostasis during pregnancy is critical to the health
      and well-being of both the mother and the developing fetus. Strikingly,
      approximately 7% of human pregnancies are characterized by insufficient insulin
      production or signaling, resulting in gestational diabetes mellitus (GDM). In
      addition to the acute health concerns of hyperglycemia, women diagnosed with GDM
      during pregnancy have an increased incidence of complications during pregnancy as
      well as an increased risk of developing type 2 diabetes (T2D) later in life.
      Furthermore, children born to mothers diagnosed with GDM have increased incidence
      of perinatal complications, including hypoglycemia, respiratory distress
      syndrome, and macrosomia, as well as an increased risk of being obese or
      developing T2D as adults. No single environmental or genetic factor is solely
      responsible for the disease; instead, a variety of risk factors, including
      weight, ethnicity, genetics, and family history, contribute to the likelihood of
      developing GDM, making the generation of animal models that fully recapitulate
      the disease difficult. Here, we discuss and critique the various animal models
      that have been generated to better understand the etiology of diabetes during
      pregnancy and its physiological impacts on both the mother and the fetus.
      Strategies utilized are diverse in nature and include the use of surgical
      manipulation, pharmacological treatment, nutritional manipulation, and genetic
      approaches in a variety of animal models. Continued development of animal models
      of GDM is essential for understanding the consequences of this disease as well as
      providing insights into potential treatments and preventative measures. 

PMID- 24085034
TI  - Ectonucleotidase NTPDase3 is abundant in pancreatic beta-cells and regulates
      glucose-induced insulin secretion.
AB  - Extracellular ATP released from pancreatic beta-cells acts as a potent
      insulinotropic agent through activation of P2 purinergic receptors.
      Ectonucleotidases, a family of membrane-bound nucleotide-metabolizing enzymes,
      regulate extracellular ATP levels by degrading ATP and related nucleotides.
      Ectonucleotidase activity affects the relative proportion of ATP and its
      metabolites, which in turn will impact the level of purinergic receptor
      stimulation exerted by extracellular ATP. Therefore, we investigated the
      expression and role of ectonucleotidases in pancreatic beta-cells. Of the
      ectonucleotidases studied, only ENTPD3 (gene encoding the NTPDase3 enzyme) mRNA
      was detected at fairly abundant levels in human and mouse pancreatic islets as
      well as in insulin-secreting MIN6 cells. ARL67156, a selective ectonucleotidase
      inhibitor, blocked degradation of extracellular ATP that was added to MIN6 cells.
      The compound also decreased degradation of endogenous ATP released from cells.
      Measurements of insulin secretion in MIN6 cells as well as in mouse and human
      pancreatic islets demonstrated that ARL67156 potentiated glucose-dependent
      insulin secretion. Downregulation of NTPDase3 expression in MIN6 cells with the
      specific siRNA replicated the effects of ARL67156 on extracellular ATP hydrolysis
      and insulin secretion. Our results demonstrate that NTPDase3 is the major
      ectonucleotidase in pancreatic beta-cells in multiple species and that it
      modulates insulin secretion by controlling activation of purinergic receptors.

PMID- 24085036
TI  - GLP-1-derived nonapeptide GLP-1(28-36)amide represses hepatic gluconeogenic gene
      expression and improves pyruvate tolerance in high-fat diet-fed mice.
AB  - Certain "degradation" products of GLP-1 were found to possess beneficial effects
      on metabolic homeostasis. Here, we investigated the function of the COOH-terminal
      fragment of GLP-1, the nonapeptide GLP-1(28-36)amide, in hepatic glucose
      metabolism. C57BL/6 mice fed a high-fat diet (HFD) for 13 wk were injected
      intraperitoneally with GLP-1(28-36)amide for 6 wk. A significant reduction in
      body weight gain in response to HFD feeding was observed in GLP-1(28-36)amide
      treated mice. GLP-1(28-36)amide administration moderately improved glucose
      disposal during glucose tolerance test but more drastically attenuated glucose
      production during pyruvate tolerance test, which was associated with reduced
      hepatic expression of the gluconeogenic genes Pck1, G6pc, and Ppargc1a. Mice
      treated with GLP-1(28-36)amide exhibited increased phosphorylation of PKA
      targets, including cAMP response element-binding protein (CREB), ATF-1, and beta
      catenin. In primary hepatocytes, GLP-1(28-36)amide reduced glucose production and
      expression of Pck1, G6pc, and Ppargc1a, which was associated with increased cAMP
      content and PKA target phosphorylation. These effects were attenuated by PKA
      inhibition. We suggest that GLP-1(28-36)amide represses hepatic gluconeogenesis
      involving the activation of components of the cAMP/PKA signaling pathway. This
      study further confirmed that GLP-1(28-36)amide possesses therapeutic potential
      for diabetes and other metabolic disorders. 

PMID- 24085035
TI  - Angiotensin type 2 receptor in pancreatic islets of adult rats: a novel
      insulinotropic mediator.
AB  - In the present study, we evaluated the relative abundance of angiotensin type 2
      receptor (AT2R) protein in various tissues of adult rats. We found that
      pancreatic islets expressed the highest AT2R protein compared with all other
      tissues. Accordingly, we then determined the functional significance of AT2R in
      the endocrine pancreas in in vivo and in vitro experiments by using angiotensin
      II (ANG II) alone, losartan (Los; AT1R antagonist), compound 21 (C21; AT2R
      agonist), and PD-123319 (PD; AT2R antagonist). Experiments carried out in rats
      indicated that, 1) ANG II treatment significantly increased plasma insulin
      concentration (1.51 +/- 0.20 vs. 0.82 +/- 0.14 ng/ml, n = 7, P < 0.05) in the fed
      state. This insulinotropic effect was further augmented by combined treatment
      with ANG II + Los (2.31 +/- 0.25 ng/ml, n = 7, P < 0.01). C21 also elevated
      insulin levels (2.13 +/- 0.20 ng/ml, n = 7, P < 0.01), which was completely
      abolished by PD. 2) ANG II impaired glucose tolerance, whereas ANG II + Los or
      C21 improved this function. 3) All treated rats displayed an enhanced insulin
      secretory response to a glucose challenge. 4) All treated rats displayed
      upregulated proinsulin 2 mRNA and insulin protein expression in the pancreas. In
      in vitro experiments using INS-1E cells and isolated rat islets, we found that
      AT2R activation significantly improved insulin biosynthesis and secretion. These
      results suggest that the AT2R functions as an insulinotropic mediator. AT2R and
      its downstream signaling pathways may be potential therapeutic targets for
      diabetes.

PMID- 24085038
TI  - Psoriasis and leprosy are teaching us T-cell plasticity.

PMID- 24085037
TI  - Mitochondrial fragmentation impairs insulin-dependent glucose uptake by
      modulating Akt activity through mitochondrial Ca2+ uptake.
AB  - Insulin is a major regulator of glucose metabolism, stimulating its mitochondrial
      oxidation in skeletal muscle cells. Mitochondria are dynamic organelles that can
      undergo structural remodeling in order to cope with these ever-changing metabolic
      demands. However, the process by which mitochondrial morphology impacts insulin
      signaling in the skeletal muscle cells remains uncertain. To address this
      question, we silenced the mitochondrial fusion proteins Mfn2 and Opa1 and
      assessed insulin-dependent responses in L6 rat skeletal muscle cells. We found
      that mitochondrial fragmentation attenuates insulin-stimulated Akt
      phosphorylation, glucose uptake and cell respiratory rate. Importantly, we found
      that insulin induces a transient rise in mitochondrial Ca(2+) uptake, which was
      attenuated by silencing Opa1 or Mfn2. Moreover, treatment with Ruthenium red, an
      inhibitor of mitochondrial Ca(2+) uptake, impairs Akt signaling without affecting
      mitochondrial dynamics. All together, these results suggest that control of
      mitochondrial Ca(2+) uptake by mitochondrial morphology is a key event for
      insulin-induced glucose uptake.

PMID- 24085039
TI  - MicroRNA-29 and an integrated understanding of atrial fibrillation.

PMID- 24085040
TI  - The use of photodynamic therapy as chemoprevention for the treatment of actinic
      keratoses and reduction in the number of non-melanoma skin cancers.

PMID- 24085041
TI  - Possible drug-drug interaction between adalimumab and duloxetine and/or
      pregabalin in a psoriasis patient.

PMID- 24085042
TI  - Adherence to ustekinumab in psoriasis patients.
AB  - BACKGROUND: Adherence to the treatment of psoriasis is poor and effects treatment
      outcomes. Literature on adherence to biologic therapy for the treatment of
      psoriasis is limited and difficult to measure. However, ustekinumab, which until
      recently was only approved to be administered in office, offers an opportunity to
      assess adherence through chart review. PURPOSE: The purpose of this study is to
      determine adherence rates and reasons for nonadherence to ustekinumab in the
      treatment of psoriasis. METHODS: This was a single center, retrospective study
      involving a chart review of patients with a diagnosis of psoriasis and
      administration of ustekinumab seen at one clinic between October 1, 2009 and June
      1, 2013. We assessed the number of injections administered, the time between
      injections, and reasons for nonadherence. RESULTS: 45 patients received
      ustekinumab for the treatment of psoriasis. The median time between doses of
      ustekinumab (n=164) was 13 weeks (91 days, interquartile range 89, 98). For
      patients that received at least 3 doses of ustekinumab, overall median adherence
      was 100% (IQR 66.7, 100). The median adherence to the 45 mg dose (n=26) was 100%
      (IQR 75, 100) and to the 90 mg dose (n=18) was 80% (IQR 60, 100; P=0.11).
      LIMITATIONS: Only limited information was found on reasons for nonadherence.
      CONCLUSIONS: Adherence to ustekinumab in psoriasis patients appears to be higher
      than reported adherence rates to topical therapies and treatment with self
      administered biologics. Many factors may contribute to the greater adherence.

PMID- 24085043
TI  - Psoriasis treatments by payment type in the US outpatient office setting.
AB  - BACKGROUND: Many factors, including patients' methods of payment, may influence
      psoriasis treatment decisions. OBJECTIVE: To characterize psoriasis treatments by
      patients' types of payment in the US outpatient office setting. METHODS: Using
      the National Ambulatory Medical Care Survey (NAMCS), a large survey that samples
      outpatient office visits to US non-federally funded physicians, visits linked
      with sole diagnoses for psoriasis (ICD-9-CM: 696.1) were identified. There were
      545 unweighted records. The types and number of treatments prescribed at these
      visits were categorized by expected major payment type to be used for the visit.
      RESULTS: Mainstay psoriasis therapies such as vitamin D analogs and clobetasol
      were prescribed regardless of payment type. Retinoids were also within the most
      frequently prescribed psoriasis medications for all payment types, however they
      were less frequently prescribed than vitamin D analogs. Payment type did not have
      a significant effect on the number of medications prescribed at psoriasis visits.
      LIMITATIONS: Data on treatment adherence and filling of prescriptions are not
      included in the NAMCS database. CONCLUSION: Prescribing patterns for psoriasis
      medications are similar across payment type. Additional factors appear to
      modulate therapy choice for patients with psoriasis.

PMID- 24085044
TI  - Combination use of ustekinumab with other systemic therapies: a retrospective
      study in a tertiary referral center.
AB  - BACKGROUND: Patients with moderate to severe psoriasis may not respond adequately
      to single systemic agent and may require combination systemic therapy. OBJECTIVE:
      To evaluate the prevalence, indications, and response to combination systemic
      therapy with ustekinumab for psoriasis in a tertiary referral center. METHODS:
      This retrospective study comprised 102 psoriasis patients treated with
      ustekinumab at a single tertiary care center. Data was collected pertaining to
      history of psoriasis, past and current therapies including use of concomitant
      psoriasis agents, response to therapy, and side effects while on ustekinumab.
      RESULTS: Twenty-two of 102 (22%) patients were identified as receiving
      combination systemic treatment involving ustekinumab and at least one additional
      agent. The most common indication for combination therapy was psoriatic arthritis
      (35%), followed by bridging therapy (26%), inadequate psoriasis control (13%),
      prevention of non-melanoma skin cancers (17%), and control of palmoplantar
      disease (9%). Methotrexate was the additional agent in 12 patients, cyclosporine
      in 7 patients, acitretin in 5 patients, and 1 patient received a second biologic
      agent, first etanercept and then adalimumab. Overall, the reduction in body
      surface area (BSA) was 80% for patients on combination therapy. For those
      patients on combination therapy for psoriatic arthritis, 75% had resolution or
      stabilization of their symptoms. Only one patient, receiving cyclosporine,
      discontinued combination therapy due to adverse side effects. CONCLUSION:
      Combination systemic therapy with ustekinumab can be effective and well tolerated
      for patients who cannot be adequately treated with ustekinumab alone.

PMID- 24085045
TI  - Nutritional clinical studies in dermatology.
AB  - BACKGROUND & AIMS: Nutrition has long been associated with skin health, beauty,
      integrity and aging through multiple pathways and cofactors implicated in skin
      biology. The onset and clinical course of various common skin diseases,
      especially acne, psoriasis, atopic dermatitis, and hair loss, have been suggested
      to be critically affected by nutrition patterns and habits. The relationship
      between acne and diet, predominantly the role of high glycemic load diets and
      dairy consumption have recently gained increased interest. Abnormal nutritional
      conditions such as obesity or malnutrition often manifest themselves by specific
      cutaneous features and altered skin function. Skin photoprotection, rendered by
      various nutrients, is well documented and appropriate nutritional supplementation
      has been shown to exert beneficial effects upon impaired skin integrity, restore
      its appearance and promote skin health. It is our intention to provide a
      comprehensive review of the most recent information on the role of nutrition for
      common skin diseases and regulation of skin biology. METHODS: Nutritional
      clinical studies in dermatology have been reviewed using the MedLine literature
      source and the terms "diet" or "nutrition" and "skin". RESULTS & CONCLUSIONS: The
      data on the relationship between nutrition and skin are until now controversial
      and much more work is needed to be done to clarify possible etiological
      correlations.

PMID- 24085046
TI  - Understanding BCC pathogenesis: treatment advancements and challenges.

PMID- 24085047
TI  - Immune response to pneumococcus and tetanus toxoid in patients with moderate-to
      severe psoriasis following long-term ustekinumab use.
AB  - BACKGROUND: Little is known about the impact of long-term use of
      immunosuppressive agents on immune response. OBJECTIVES: Assess the impact of
      continuous maintenance ustekinumab treatment on patients' ability to mount immune
      responses to pneumococcal (T-cell-independent) and tetanus toxoid (T-cell
      dependent) vaccines. PATIENTS AND METHODS: Ustekinumab-treated patients with
      moderate-to-severe psoriasis treated in the long-term extension of the Phase 3
      PHOENIX 2 trial (n=60) were compared with control psoriasis patients not
      receiving systemic therapy (n=56). Patients were vaccinated with both 23-valent
      pneumococcal and tetanus toxoid vaccines. Serum samples collected pre-vaccination
      and 4 weeks post-vaccination were assessed for antibody responses. RESULTS: No
      differences in the ability of ustekinumab-treated patients to respond to
      pneumococcal or tetanus toxoid vaccinations were observed compared with controls.
      A >=2-fold increase in antibody levels in >=7 of 14 serotypes of the pneumococcal
      vaccine was observed in ustekinumab-treated (96.6%) and untreated control (92.6%)
      patients following vaccination. Ustekinumab-treated patients achieved a >=4-fold
      increase (84.7%) in anti-tetanus antibody vs. 77.8% in the control group. No
      differences were detected in ex-vivo responses to anti-CD3/CD28 or tetanus toxoid
      between ustekinumab-treated and control groups. CONCLUSION: Long-term treatment
      (>=3 years) with ustekinumab does not compromise the immune response to T-cell
      dependent/-independent vaccines in patients with moderate-to-severe psoriasis.

PMID- 24085048
TI  - Curcumin: a novel treatment for skin-related disorders.
AB  - Curcumin, or diferuloylmethane, is a crystalline compound which gives the East
      Asian spice turmeric its bright yellow color. The medicinal properties of this
      spice have been referenced in numerous countries and cultures throughout the
      world. Today, there is growing scientific evidence suggesting curcumin's utility
      in the treatment of chronic pain, inflammatory dermatoses, acceleration of wound
      closure, skin infections, as well as cosmetic ailments such as dyspigmentation.
      In addition, curcumin may have a protective role against various pollutants and
      cytotoxic agents, indicating that it may be beneficial in a mitigational or
      prophylaxis role. Although turmeric has been used for thousands of years in
      alternative medicine, curcumin has yet to emerge as a component of our mainstream
      dermatologic therapeutic armamentarium. Interestingly, curcumin provides an ideal
      alternative to current therapies because of its relative safety profile even at
      high doses. Although the advantageous properties of curcumin in medicine are well
      established, its therapeutic potential thus far has been limited because of its
      poor oral bioavailablity. Topical administration of curcumin can directly deliver
      it to the affected tissue making it useful in treating skin-related disorders.
      However, limitations still exist such as the cosmetically unpleasing bright
      yellow-orange color, its poor solubility, and its poor stability at a high pH.
      Here the current literature detailing the potential and current use of curcumin
      in dermatology is reviewed.

PMID- 24085049
TI  - Purpura and fillers: a review of pre-procedural, intra-procedural, and post
      procedural considerations.
AB  - Injectable aesthetic fillers are associated with the common and expected side
      effect of purpura or bruising. There are pre-procedural, intra-procedural and
      post-procedural considerations that can potentially minimize bruising.
      Traditional and newer techniques are discussed in this review and the benefits
      and risks of each technique will be provided.

PMID- 24085050
TI  - Pimecrolimus cream and Tacrolimus ointment in the treatment of atopic dermatitis:
      a pilot study on patient preference.
AB  - BACKGROUND: Pimecrolimus cream 1% is approved for mild to moderate atopic
      dermatitis in children older than two years of age and adults. Tacrolimus
      ointment 0.03% is approved for moderate to severe atopic dermatitis in the
      patient population between two to seventeen years of age and Tacrolimus 0.1%
      ointment for moderate to severe atopic dermatitis in patients 18 years of age and
      older. However, beyond safety and efficacy, the delivery system or vehicle used
      in topical treatment formulations is equally important in affecting patient
      satisfaction, tolerability, and subsequent treatment compliance and hence
      clinical resolution of active disease.

PMID- 24085051
TI  - Efficacy of combination of glycolic acid peeling with topical regimen in
      treatment of melasma.
AB  - BACKGROUND: Various treatment modalities are available for management of melasma,
      ranging from topical and oral to chemical peeling, but none is promising alone.
      Very few studies are available regarding efficacy of combination of topical
      treatment with chemical peeling. Combination of chemical peeling and topical
      regimen can be a good treatment modality in the management of this recalcitrant
      disorder. OBJECTIVE: To assess the efficacy of combination of topical regimen (2%
      hydroquinone, 1% hydrocortisone and 0.05% tretinoin) with serial glycolic acid
      peeling in the treatment of melasma in Indian patients. METHODS: Forty Indian
      patients of moderate to severe epidermal variety melasma were divided into two
      groups of 20 each. One Group i.e. peel group received topical regimen (2%
      hydroquinone, 1% hydrocortisone and 0.05% tretinoin) with serial glycolic acid
      peeling and other group i.e. control group received topical regimen (2%
      hydroquinone, 1% hydrocortisone, 0.05% tretinoin). RESULTS: There was an overall
      decrease in MASI from baseline in 24 weeks of therapy in both the groups (P value
      < 0.05). The group receiving the glycolic acid peel with topical regimen showed
      early and greater improvement than the group which was receiving topical regimen
      only. CONCLUSION: This study concluded that combining topical regimen (2%
      hydroquinone, 1% hydrocortisone and 0.05% tretinoin) with serial glycolic acid
      peeling significantly enhances the therapeutic efficacy of glycolic acid peeling.
      The combination of glycolic acid peeling with the topical regimen is a highly
      effective, safe and promising therapeutic option in treatment of melasma.

PMID- 24085052
TI  - Valrubicin activates PKCa in keratinocytes: a conceivable mode of action in
      treating hyper-proliferative skin diseases.
AB  - BACKGROUND: Valrubicin is a semisynthetic anthracycline developed as an anti
      cancer drug able to ameliorate psoriasis and non-melanoma skin cancer (NMSC) by
      topical application in animal models. Valrubicin decreases cell proliferation,
      and induces apoptosis; however its mode of action is still unknown. Valrubicin
      localizes in the cytoplasm and its valerate moiety resembles diacylglycerol, an
      activator of protein kinase C (PKC) alpha, which belongs to the PKC family of
      cytoplasmic serine/threonine protein kinases. PKCalpha is observed in the
      suprabasal layers of normal skin and is associated to keratinocyte growth arrest
      and differentiation processes. In hyper-proliferative skin diseases the presence
      of PKCalpha is altered. OBJECTIVE: The aim of the present study was to
      investigate valrubicin's mode of action in keratinocytes by studying its possible
      effect on PKCalpha activation. METHODS: PKCalpha's characteristic to translocate
      from the cytoplasm to the cellular membrane when activated was assessed by
      measuring the amount of PKCalpha in the soluble and membrane-bound protein
      fractions isolated from valrubicin stimulated keratinocytes and by visualizing
      PKCalpha in stimulated cells over time. Downstream signaling was investigated by
      measuring the amount of phosphorylated Myristoylated Alanine-rich C-kinase
      substrate (MARCKS) and extracellular signal-regulated kinases (ERK) 1/2 of
      valrubicin-stimulated keratinocytes. To investigate whether there was a direct
      interaction between valrubicin and PKCalpha, an activity assay employing purified
      PKCalpha protein was used. RESULTS: Valrubicin activates PKCalpha in vitro as
      shown by PKCalpha's translocation and phosphorylation of downstream signaling
      molecules. CONCLUSION: Valrubicin stimulates PKCalpha activity and downstream
      signaling which may contribute to its beneficial effect in psoriasis and NMSC.

PMID- 24085053
TI  - Focal Acne Scar Treatment (FAST), a new approach to atrophic acne scars: a case
      series.
AB  - BACKGROUND: Acne scars are a common concern in dermatology. Fractional CO2 laser
      resurfacing is a recent addition in our armamentarium of treatment options for
      acne scars and has been shown to be an excellent option for patients with
      atrophic acne scars. Patients with acne scars receiving fractional CO2
      resurfacing usually have both the acne scars and surrounding unscarred areas
      treated in common practice. There has yet to be a study that looked at the
      implications of only focally treating the acne scars while leaving surrounding
      normal skin untreated. OBJECTIVE: To evaluate the safety and efficacy of a focal
      approach to fractional CO2 laser treatment for acne scars, coined "Focal Acne
      Scar Treatment" or "FAST" PATIENTS AND METHODS: This retrospective case series
      was conducted at Schweiger Dermatology, in New York, NY, with patients treated
      from November 2011 through May 2012. Overall, six patients (ages 18 to 48) were
      treated with the fractional CO2 laser resurfacing, using a so called "FAST"
      technique treating only the acne scars and leaving normal skin untreated.
      Evaluation was based on physician and patient assessment of improvement at one
      week and four weeks post-treatment. RESULTS: All six patients treated with the
      Focal Acne Scar Treatment technique of fractional CO2 laser resurfacing had
      significant improvement post treatment ranging from 40% to 70% as estimated by
      the treating dermatologist and patient at four weeks post treatment. Patient
      satisfaction was high following FAST method. Temporary post-inflammatory
      hyperpigmentation was seen in two patients but resolved after a single 1550 nm
      Erbium Glass fractional laser treatment. CONCLUSION: The Focal Acne Scar
      Treatment technique is an effective method of improving the appearance of
      atrophic acne scars. Higher energy and density levels can be used when utilizing
      this technique, resulting in improved outcomes when compared with whole face
      fractional CO2 laser resurfacing. Healing is improved and faster with this
      technique and no increased incidence of permanent adverse events were found. More
      studies are needed to further evaluate this new technique.

PMID- 24085054
TI  - Etanercept urticaria in a patient with psoriasis desensitized using a new method.
AB  - Desensitization is the process of rendering an individual who is allergic to a
      food or chemical substance like a drug able to tolerate the agent. This is
      usually accomplished by exposing the patient to incrementally increasing doses,
      injecting the offending agent over periods of time as is done in situations of
      grass or tree pollen allergy. In the current case report we demonstrate the first
      method to desensitize a patient to the anti-TNF medicament etanercept using
      immune suppressants rather than the older technique of incrementally increasing
      injection doses.

PMID- 24085055
TI  - Minimizing skin cancer surgical scars using ablative fractional Er:YAG laser
      treatment.
AB  - BACKGROUND AND OBJECTIVE: Scars from skin cancer surgery on the face can be quite
      prominent and not easily obscured by makeup. This report evaluates the use of an
      ablative fractional Er:YAG laser device for minimizing or blending scar lines in
      two patients who underwent repair of skin cancer defects on the face. METHODS:
      Two patients underwent surgery to remove facial skin cancer tumors. The resulting
      scars after reconstruction of these skin cancer defects on the left cheek (Case
      1) and right cheek (Case 2) each received 3 treatments with a fractional ablative
      laser device (ProFractional-XC, Sciton, Inc., Palo Alto, CA). Treatments were
      spaced about 1 month apart. Topical anesthetic cream applied 1 hour before
      treatment minimized patient discomfort during the procedure. Treatment depths
      ranged from 150 to 200 microns, 2 passes were performed, and coverage per pass
      was typically 22% and then 11% in the coagulation mode. Results were evaluated by
      digital photography before the initial treatment, approximately 4-5 weeks after
      each of the 3 treatments, and at approximately 7 months after the surgical
      procedures. RESULTS: The fractional Er:YAG laser device significantly improved
      postsurgical scar lines in each patient without significant adverse effects.
      Prior to the laser sessions, these scars demonstrated hypopigmentation,
      hyperpigmentation, neovascularization, or diminished pore structures compared to
      the surrounding skin. These pigmentary, vascular or textural issues were all
      significantly improved by the fractional ablative Er:YAG laser. CONCLUSION: The
      ablative fractional laser device of the present report safely minimizes and
      improves facial scars demonstrating not only textural alterations but also some
      pigmentary and vascular changes after reconstruction of skin cancer defects.

PMID- 24085056
TI  - A novel anti-inflammatory in treatment of acne vulgaris: the pseudopterosins.
AB  - The pseudopterosins derived from the marine gorgonian octocoral, P. elisabethae
      are novel biologically active compounds increasingly recognized for their anti
      inflammatory, analgesic, and wound healing properties among other clinical
      attributes yet to be discovered. These and a multitude of other natural products
      derived from the sea are now being harnessed and advanced for their biological
      activity and promising therapeutic benefits. With continued research, the
      enormous potential for using these compounds in managing acute and chronic
      inflammatory cutaneous disorders is both exciting and inevitable.

PMID- 24085057
TI  - Post-filler vascular occlusion: a cautionary tale and emphasis for early
      intervention.
AB  - We report a case of a 36-year-old female who experienced significant vascular
      occlusion after injection with hyaluronic acid into the nasolabial folds. The
      patient experienced immediate pain after the injection, however, the vascular
      compromise was not diagnosed and treated until 48 hours later. The patient
      suffered tissue damage despite treatment with hyaluronidase, hyperbaric oxygen,
      nitropaste, and aspirin. The case highlights the importance of proper injection
      technique by a qualified physician, as well as the need for immediate recognition
      and treatment of vascular occlusion should it occur.

PMID- 24085058
TI  - News, views and reviews.

PMID- 24085059
TI  - Advanced basal cell carcinoma: therapeutic options and considerations for patient
      care. Introduction.

PMID- 24085060
TI  - Treatment of margin positive basal cell carcinoma with vismodegib: case report
      and consideration of treatment options and their implications.
AB  - Historically, basal cell carcinomas (BCCs) that are neither surgically resectable
      nor candidates for radiation therapy have had few treatment options. The hedgehog
      pathway inhibitor, vismodegib, represents a new opportunity for the treatment of
      such patients. Vismodegib has approval from the United States Food and Drug
      Administration for treatment of metastatic BCC, locally advanced BCC recurring
      after surgery, and BCC that is not treatable via surgery or radiation. We present
      the case of a patient with a BCC infiltrating the spinal column that was neither
      possible to fully remove surgically nor a candidate for primary treatment with
      radiation. Treatment with vismodegib followed by adjuvant radiation therapy
      resulted in complete disease clearance. Vismodegib represents a promising
      treatment option for patients with surgically non-resectable BCCs that are not
      candidates for radiation therapy. Mechanism of action, benefits, and adverse
      events of vismodegib are reviewed, along with a brief discussion on newer options
      in the hedgehog inhibitor class.

PMID- 24085061
TI  - The impact of inoperable advanced basal cell carcinoma: the economic, physical,
      and psychological burden of the disease.
AB  - The development of vismodegib and its recent approval by the United States Food
      and Drug Administration for use in patients with locally advanced or metastatic
      basal cell carcinoma (BCC) carries with it a renewed sense of optimism. Once BCC
      has progressed to an advanced, or so-called inoperable stage, there has been a
      paucity of effective therapies, making the new small molecule inhibitors
      targeting the hedgehog pathway particularly hopeful prospects. In order to better
      understand the utility of these new treatments, it is important to assess the
      existing economic, physical, and psychological burden of advanced BCC. This
      review aims to recognize the impact of inoperable and metastatic BCC, as well as
      to better characterize the various types of advanced BCC. The use of vismodegib
      as a prophylactic treatment in patients with basal cell nevus syndrome is also
      addressed, including possible adverse events, tumor resistance, and new onset
      malignancies.

PMID- 24085062
TI  - Vismodegib: a hedgehog pathway inhibitor for locally advanced and metastatic
      basal cell carcinomas.
AB  - Basal cell carcinomas (BCCs) are the most common cancer in the United States, and
      the overwhelming majority of BCCs are the result of hedgehog pathway activation.
      While locally advanced and metastatic BCC are rare, currently available
      treatments remain limited and are often unsuccessful. Vismodegib inhibits a key
      regulatory protein in the hedgehog pathway and was approved by the United States
      Food and Drug Administration in 2012. This orally-administered medication offers
      a novel approach for treating locally advanced and metastatic BCC. The following
      review will address vismodegib's mechanism of action, published clinical trial
      data, and the questions that still remain unanswered about this new medication.

PMID- 24085063
TI  - Single molecule methods for the study of catalysis: from enzymes to heterogeneous
      catalysts.
AB  - Structural and temporal inhomogeneities can have a marked influence on the
      performance of inorganic and biocatalytic systems alike. While these subtle
      variations are hardly ever accessible through bulk or ensemble averaged activity
      screening, insights into the molecular mechanisms underlying these diverse
      phenomena are absolutely critical for the development of optimized or novel
      catalytic systems and processes. Fortunately, state-of-the-art fluorescence
      microscopy methods have allowed experimental access to this intriguing world at
      the nanoscale. In this tutorial review we will first provide a broad overview of
      key concepts and developments in the application of single molecule fluorescence
      spectroscopy to (bio)catalysis research. In the second part topics specific to
      both bio and heterogeneous catalysis will be reviewed in more detail. 

PMID- 24085064
TI  - Optical parametric amplification in one-dimensional photonic bandgap structures.
AB  - In this paper, optical parametric amplification based on the degenerate four-wave
      mixing principle in a one-dimensional photonic bandgap (PBG) structure has been
      numerically studied. First, the multiple scale method was introduced to derive a
      complete set of nonlinear coupled-mode equations for a finite structure with
      different inhomogeneous nonlinear coefficients than those used in previous works.
      This finite structure is composed of 680 dielectric layers, which are alternating
      half-wave/eight-wave films. The wavelengths of the pump, signal, and idler pulses
      have been determined from the transmission spectrum, which was illustrated by
      using the transfer matrix method. The parametric interaction of the pump, signal,
      and idler pulses inside PBG structure has been numerically simulated by using the
      split-step Fourier transform method. The results of the simulation have shown
      that the intensities of the signal and idler have exponential growth with respect
      to the number of layers in the medium. Meanwhile, pump wavevector detuning
      directly affects the intensities of both pulses due to a band-edge phase-matching
      condition that might be achieved from only one optimal detuning parameter.
      Moreover, both the amplification gain and the conversion efficiency of the idler
      pulse have been shown to be dependent on the bandwidth of the pump pulse
      spectrum. A very narrow pulse, with a bandwidth much less than the relevant
      transmission peak, enables the highest amplification and conversion efficiency in
      this medium because the most efficient phase-matched condition occurs in this
      situation. Finally, the conversion efficiency grows exponentially with input pump
      intensity for several input signal intensities. Furthermore, the maximum
      conversion efficiencies directly vary with input signal intensity. 

PMID- 24085065
TI  - Polarized infrared reflectivity of one-dimensional Gaussian sea surfaces with
      surface reflections.
AB  - Sea surface infrared reflectivity is an important parameter in maritime remote
      sensing. Usually, single reflection by the sea surface is considered. However, a
      loss of energy is then reported for large zenith observation angles (theta>50
      degrees ) with a peak of about 4% for theta~80 degrees , because of the neglect
      of the multiple surface reflections. This paper presents calculations for the
      polarized infrared reflectivity of one-dimensional sea surfaces (2D problems)
      with two surface reflections, by introducing a bistatic illumination function
      with two reflections. The results show good agreement with the ones obtained by a
      Monte Carlo ray-tracing method. It is also shown that the energy conservation
      criterion is better satisfied after considering two surface reflections. 

PMID- 24085066
TI  - Control of polariton spectrum in bigyrotropic medium.
AB  - The ion and electron polarizations under the influence of high-frequency
      electromagnetic field and external magnetostatic field in a bigyrotropic medium
      (dielectric with magnetic subsystem) are considered. The polariton spectra in the
      bigyrotropic medium are received. It is shown that the polariton spectrum and the
      velocity of polariton wave can be controlled by the variation of the intensity
      and direction of external magnetostatic field. It becomes possible because the
      ion and electron Larmor's frequencies depend on the external magnetostatic field
      that leads to the appearance of several additional resonances of the permittivity
      and permeability of the medium. The wave vector and velocity of polariton wave
      that are close to the resonance frequencies vary depending on the wave frequency:
      the polariton wave velocity drops to zero before the resonance and increases
      after it. The wave velocity control may be used for designing controllable
      devices for a data-transmitting line. 

PMID- 24085067
TI  - Liquid-crystal phase-shifting lateral shearing interferometer with improved
      fringe contrast for 3D surface profilometry.
AB  - We report the development of a common-path and nonmechanical scanning phase
      shifting lateral shearing interferometer based on a homogeneous gap and wedge
      shaped gap liquid-crystal (LC) cell. The modified cell consists of semi
      reflecting and fully reflecting glass plates with LC material sandwiched between
      them so that the amount of reflected light from both the surfaces is nearly
      equal, thus generating high contrast interference fringes. The thickness of the
      LC cell was maintained at ~3 MUm uniformly for a homogeneous gap and a varying
      wedge gap was also introduced between two glass plates. Phase-shifting linear
      fringe patterns of high contrast were generated. The phase-shifted interferograms
      were projected onto an object and the distorted interferograms were recorded by a
      CCD camera. The phase-shifting fringe analysis technique was used to reconstruct
      the 3D shape of the object. The present system is compact and low cost.

PMID- 24085068
TI  - Stability and normal incidence reflectivity of W/B4C multilayer mirror near the
      boron K absorption edge.
AB  - A multilayer structure consisting of alternate layers of W and B4C has been
      deposited using a magnetron sputtering system. The structure of the as-deposited
      and vacuum-annealed W/B4C multilayer sample has been characterized using grazing
      incidence x-ray reflectivity, grazing incidence diffraction, and the normal
      incidence reflectivity has been measured using synchrotron radiation. A two-layer
      model consisting of tungsten and boron carbide is presented. The multilayer
      structure was found to be stable after 800 degrees C annealing. Grazing incidence
      x-ray diffraction measurements suggested that W is polycrystalline with small
      grain size. No signature of tungsten carbide or tungsten boride formation could
      be observed during the annealing treatments. A near normal incidence soft x-ray
      reflectivity (SXRR) of ~8.3% was obtained at 6.8 nm wavelength. A little drop
      (~1%) in SXRR after 800 degrees C annealing suggested that there were no
      compositional changes within the layers during the annealing treatments.

PMID- 24085069
TI  - All-optical controlled switching in centrally coupled circular array of nonlinear
      optical fibers.
AB  - We show that, in a nonlinear centrally coupled circular array of evanescently
      coupled fibers, the coupling dynamics of a weak signal beam can be efficiently
      influenced by a high-power control beam that induces nonlinear defects. When the
      intense control beam is launched into the central core and one core in the
      periphery, then localized solitons are formed and cause the fibers with induced
      defects (defected fibers) to decouple from the other array elements. In the
      presence of a high-intensity control beam, the propagation of weak signal is
      restricted to the defected optical fibers. The weak signal periodically couples
      between the induced defects. This oscillatory behavior depends on the sign of the
      (Kerr-type) nonlinearity and the initial phase difference between the control
      fields injected to the central and one of the peripheral fibers. This all-optical
      network has the advantage of routing and switching the weak signal field in a
      controlled way by adjusting the parameters of intense control field. 

PMID- 24085070
TI  - 3D palmprint and hand imaging system based on full-field composite color
      sinusoidal fringe projection technique.
AB  - Palmprint and hand shape, as two kinds of important biometric characteristics,
      have been widely studied and applied to human identity recognition. The existing
      research is based mainly on 2D images, which lose the third-dimensional
      information. The biological features extracted from 2D images are distorted by
      pressure and rolling, so the subsequent feature matching and recognition are
      inaccurate. This paper presents a method to acquire accurate 3D shapes of
      palmprint and hand by projecting full-field composite color sinusoidal fringe
      patterns and the corresponding color texture information. A 3D imaging system is
      designed to capture and process the full-field composite color fringe patterns on
      hand surface. Composite color fringe patterns having the optimum three fringe
      numbers are generated by software and projected onto the surface of human hand by
      a digital light processing projector. From another viewpoint, a color CCD camera
      captures the deformed fringe patterns and saves them for postprocessing. After
      compensating for the cross talk and chromatic aberration between color channels,
      three fringe patterns are extracted from three color channels of a captured
      composite color image. Wrapped phase information can be calculated from the
      sinusoidal fringe patterns with high precision. At the same time, the absolute
      phase of each pixel is determined by the optimum three-fringe selection method.
      After building up the relationship between absolute phase map and 3D shape data,
      the 3D palmprint and hand are obtained. Color texture information can be directly
      captured or demodulated from the captured composite fringe pattern images.
      Experimental results show that the proposed method and system can yield accurate
      3D shape and color texture information of the palmprint and hand shape. 

PMID- 24085071
TI  - HyDRa: polishing with a vortex.
AB  - We present a hydrodynamic, deterministic polishing tool (HyDRa) based on the
      fluid-jet polishing (FJP) principle. In contrast to other FJP methods, the
      polishing flux is accelerated with pressurized air and then expelled at high
      velocity, forming a radial, grazing abrasive pattern that exerts no net force of
      the tool on the surface to be polished, since the vacuum and thrust forces that
      are created at the tool's output balance each other out. The grazing effect
      minimizes microroughness, making it appropriate for finishing high-quality
      surfaces. The principle of operation as well as polishing results of a series of
      small etalon plates are presented. 

PMID- 24085072
TI  - Subharmonics and chaos generation in all-fiber phase modulator: experimental and
      theoretical analyses with simulation.
AB  - We report the results of experimental observation and theoretical analysis of the
      generation of subharmonic and chaotic signals in a harmonically driven all-fiber
      phase modulator (PM). When a PM constructed with optical fiber wrapped around a
      piezoelectric cylinder is driven at high amplitude, we identified that the fiber
      itself moves with subharmonic frequencies while the piezoelectric cylinder
      maintains harmonic motion. A theoretical model is presented that is a
      modification of the model for a bouncing ball on an oscillating table. Some key
      physical parameters for the model are identified. Potential origins for the
      discrepancy between the experimental and theoretical analyses are discussed. Ways
      to suppress the nonlinear effect are also discussed. 

PMID- 24085073
TI  - Investigations of the fabrication and the surface-enhanced Raman scattering
      detection applications for tapered fiber probes prepared with the laser-induced
      chemical deposition method.
AB  - The process of depositing nanoparticles onto tapered fiber probes with the laser
      induced chemical deposition method (LICDM) and the surface-enhanced Raman
      scattering (SERS) detection performance of the prepared probes are experimentally
      investigated in this paper. Our results show that the nanoparticle-deposited
      tapered fiber probes prepared with the LICDM method depend strongly on the value
      of the cone angle. For small-angle tapered probes the nanoparticle-deposited
      areas are only focused at the taper tips, because the taper surfaces are mainly
      covered by a relatively low-intensity evanescent field. By lengthening the
      reaction time or increasing the induced power or solution concentration, it is
      still possible to deposit nanoparticles on small-angle tapers with the light
      scattering effect. With 4-aminothiophenol as the testing molecule, it was found
      that for given preparation conditions, the cone angles for the tapered probes
      with the highest SERS spectral intensities for different excitation laser powers
      are almost the same. However, such an optimal cone angle is determined by the
      combined effects of both the localized surface plasmon resonance strength and the
      transmission loss generated by the nanoparticles deposited. 

PMID- 24085074
TI  - Simultaneous nonlinear encryption of grayscale and color images based on phase
      truncated fractional Fourier transform and optical superposition principle.
AB  - A nonlinear color and grayscale images cryptosystem based on phase-truncated
      fractional Fourier transform and optical superposition principle is proposed. In
      order to realize simultaneous encryption of color and grayscale images, each
      grayscale image is first converted into two phase masks by using an optical
      coherent superposition, one of which is treated as a part of input information
      that will be fractional Fourier transformed while the other in the form of a
      chaotic random phase mask (CRPM) is used as a decryption key. For the purpose of
      optical performance, all the processes are performed through three channels,
      i.e., red, green, and blue. Different from most asymmetric encryption methods,
      the decryption process is designed to be linear for the sake of effective
      decryption. The encryption level of a double random phase encryption based on
      phase-truncated Fourier transform is enhanced by extending it into fractional
      Fourier domain and the load of the keys management and transmission is lightened
      by using CRPMs. The security of the proposed cryptosystem is discussed and
      computer simulation results are presented to verify the validity of the proposed
      method. 

PMID- 24085075
TI  - Brillouin optical spectrum analyzer monitoring of subcarrier-multiplexed fiber
      optic signals.
AB  - Optical spectral analysis of closely spaced, subcarrier multiplexed fiber-optic
      transmission is performed, based on stimulated Brillouin scattering (SBS). The
      Brillouin gain window of a single, continuous-wave pump is scanned across the
      spectral extent of the signal under test. The polarization pulling effect
      associated with SBS is employed to improve the rejection ratio of the analysis by
      an order of magnitude. Ten tones, spaced by only 10 MHz and each carrying random
      sequence on-off keying data, are clearly resolved. The measurement identifies the
      absence of a single subcarrier, directly in the optical domain. The results are
      applicable to the monitoring of optical orthogonal frequency domain multiplexing
      and radio over fiber transmission.

PMID- 24085076
TI  - Orientation with a Viking sun-compass, a shadow-stick, and two calcite sunstones
      under various weather conditions.
AB  - It is widely accepted that Vikings used sun-compasses to derive true directions
      from the cast shadow of a gnomon. It has been hypothesized that when a cast
      shadow was not formed, Viking navigators relied on crude skylight polarimetry
      with the aid of dichroic or birefringent crystals, called "sunstones." We
      demonstrate here that a simple tool, that we call "shadow-stick," could have
      allowed orientation by a sun-compass with satisfying accuracy when shadows were
      not formed, but the sun position could have reliably been estimated. In field
      tests, we performed orientation trials with a set composed of a sun-compass, two
      calcite sunstones, and a shadow-stick. We show here that such a set could have
      been an effective orientation tool for Vikings only when clear, blue patches of
      the sky were visible. 

PMID- 24085077
TI  - Simple, reliable, and nondestructive method for the measurement of vacuum
      pressure without specialized equipment.
AB  - We present a simple, reliable, and nondestructive method for the measurement of
      vacuum pressure in a magneto-optical trap. The vacuum pressure is verified to be
      proportional to the collision rate constant between cold atoms and the background
      gas with a coefficient k, which can be calculated by means of the simple ideal
      gas law. The rate constant for loss due to collisions with all background gases
      can be derived from the total collision loss rate by a series of loading curves
      of cold atoms under different trapping laser intensities. The presented method is
      also applicable for other cold atomic systems and meets the miniaturization
      requirement of commercial applications. 

PMID- 24085078
TI  - Imaging system to assess objectively the optical density of the macular pigment
      in vivo.
AB  - This paper presents an optical system called MacPI, which implements a two-color
      reflectance technique in combination with various hardware and software tools to
      assess objectively the macular pigment (MP) optical density in vivo. The system
      consists of a bespoke optical design, a control architecture, driver electronics,
      a collection of image-processing techniques, and a graphical user interface. The
      deficiencies of the technique employed and the solutions implemented in the MacPI
      system to confront those inherent frailties are presented. An overview of the
      effective interpretation of the acquired data and the techniques employed by
      MacPI in the acquisition of that data is discussed. The result of a comparison
      trial with an alternative device is also presented. We suggest that appropriate
      design of the hardware and an efficient interpretation of the acquired data
      should produce a system capable of consistent, accurate, and rapid measurements,
      while retaining the distinction of ease of use, portability, comfort for the
      subject, and a design that is economic to produce. Its versatility should allow
      both for a clinical screening application and for further investigation and
      establishment of the physiological role of the MP in a laboratory-based
      environment. 

PMID- 24085079
TI  - Optical Hash function based on two-beam interference.
AB  - An approach for constructing an optical Hash function, also known as a one-way
      cryptosystem, based on two-beam interference (OHF-TBI) is proposed. The purpose
      of this method is creating the "digital fingerprint" of any precoding message
      with arbitrary length. This approach consists of three steps, in which the main
      step is a one-way processing procedure with a compression mechanism. To achieve
      the function of one-way property and compressibility, we designed a cascaded
      process on the basis of the two-beam interference principle and phase-truncation
      operation. The performance of the mentioned OHF-TBI is verified by theoretical
      analysis and a set of numerical simulations. 

PMID- 24085080
TI  - Simulation of diffuse photon migration in tissue by a Monte Carlo method derived
      from the optical scattering of spheroids.
AB  - A Monte Carlo method was derived from the optical scattering properties of
      spheroidal particles and used for modeling diffuse photon migration in biological
      tissue. The spheroidal scattering solution used a separation of variables
      approach and numerical calculation of the light intensity as a function of the
      scattering angle. A Monte Carlo algorithm was then developed which utilized the
      scattering solution to determine successive photon trajectories in a three
      dimensional simulation of optical diffusion and resultant scattering intensities
      in virtual tissue. Monte Carlo simulations using isotropic randomization, Henyey
      Greenstein phase functions, and spherical Mie scattering were additionally
      developed and used for comparison to the spheroidal method. Intensity profiles
      extracted from diffusion simulations showed that the four models differed
      significantly. The depth of scattering extinction varied widely among the four
      models, with the isotropic, spherical, spheroidal, and phase function models
      displaying total extinction at depths of 3.62, 2.83, 3.28, and 1.95 cm,
      respectively. The results suggest that advanced scattering simulations could be
      used as a diagnostic tool by distinguishing specific cellular structures in the
      diffused signal. For example, simulations could be used to detect large
      concentrations of deformed cell nuclei indicative of early stage cancer. The
      presented technique is proposed to be a more physical description of photon
      migration than existing phase function methods. This is attributed to the
      spheroidal structure of highly scattering mitochondria and elongation of the cell
      nucleus, which occurs in the initial phases of certain cancers. The potential
      applications of the model and its importance to diffusive imaging techniques are
      discussed.

PMID- 24085081
TI  - Generation of an array of optical bottle beams using a superposition of Bessel
      beams.
AB  - A procedure for computing the phase transmission function of diffractive optical
      elements intended to form an array of optical bottle beams is proposed and
      studied. The procedure is based on a superposition of Bessel beams. We show that
      the hollow circular beams (optical bottle beams) are suited for trapping
      transparent spherical micro-objects matched in radius with the beam radius. A
      series of experiments on trapping transparent micro-objects in the optical bottle
      arrays is described. Results of an experiment on trapping opaque spherical
      microparticles in a double optical bottle are reported. 

PMID- 24085082
TI  - Polydimethylsiloxane thin film characterization using all-optical photoacoustic
      mechanism.
AB  - This paper presents a nondestructive ultrasound testing method for
      characterization of the resonant frequencies of polydimethylsiloxane (PDMS) thin
      film by using a miniature fiber optic photoacoustic (PA) probe. The PA probe was
      fabricated with an optical fiber and a synthesized gold nanocomposite. During the
      experiment, a cured PDMS thin film with a thickness of 220 MUm was immersed into
      a water medium using a custom-designed holder to clamp the film. An acoustic
      pulse was generated by the PA probe and propagated through the water media to
      excite the fixed film. A fiber optic pressure sensor based on the Fabry-Perot
      principle was used to collect the excited acoustic signals on the other side of
      the film. The acquired response of the acoustic pulse was used to compute the
      resonant frequencies of the PDMS thin film based on a deconvolution method.

PMID- 24085083
TI  - Variable optical attenuator based on photonic crystal waveguide with low-group
      index tapers.
AB  - We demonstrate a compact thermo-optic variable optical attenuator (VOA) based on
      the cutoff effect of W1 photonic crystal waveguide (PCW). In experiment, a
      variable attenuation range of 29 dB is achieved with a device length of only 16.8
      MUm. The coupling loss is also reduced by 7.5+/-2.5 dB through introducing low
      group-index tapers between the W1 PCW and strip waveguide. This VOA provides the
      largest variable attenuation range in the reported tunable PCW device to our
      knowledge.

PMID- 24085084
TI  - Detection of Earth-rotation Doppler shift from Suomi National Polar-Orbiting
      Partnership Cross-Track Infrared Sounder.
AB  - The Cross-Track Infrared Sounder (CrIS) on the Suomi National Polar-Orbiting
      Partnership Satellite is a Fourier transform spectrometer and provides a total of
      1305 channels for sounding the atmosphere. Quantifying the CrIS spectral
      accuracy, which is directly related to radiometric accuracy, is crucial for
      improving its data assimilation in numerical weather prediction. In this study, a
      cross-correlation method is used for detecting the effect of Earth-rotation
      Doppler shift (ERDS) on CrIS observations. Based on a theoretical calculation,
      the ERDS can be as large as about 1.3 parts in 10(6) (ppm) near Earth's equator
      and at the satellite scan edge for a field of regard (FOR) of 1 or 30. The CrIS
      observations exhibit a relative Doppler shift as large as 2.6 ppm for a FOR pair
      of 1 and 30 near the equator. The variation of the ERDS with latitude and scan
      position detected from CrIS observations is similar to that derived
      theoretically, which indicates that the spectral stability of the CrIS instrument
      is very high. To accurately calibrate CrIS spectral accuracy, the ERDS effect
      should be removed. Since the ERDS is easily predictable, the Doppler shift is
      correctable in the CrIS spectra.

PMID- 24085085
TI  - Rotation of principal axes and birefringence in III-V lasers owing to bonding
      strain.
AB  - Measurements of the degree of polarization (DOP) of photoluminescence from the
      facets of bonded III-V semiconductor diode laser chips show shear strain. The
      effect of shear strain on the refractive index is investigated. Finite element
      method (FEM) simulations are matched to the facet map of the DOP for a bonded
      GaAs chip and are used to extract estimates of the strain induced by die attach.
      Given estimates of the strains from the FEM simulations, changes in the
      refractive indices and rotations of the principal axes are calculated for the
      chip. This work has value in understanding operational changes owing to bonding
      induced strain. 

PMID- 24085086
TI  - Shutterless solution for simultaneous focal plane array temperature estimation
      and nonuniformity correction in uncooled long-wave infrared camera.
AB  - In uncooled long-wave infrared (LWIR) microbolometer imaging systems, temperature
      fluctuations of the focal plane array (FPA) result in thermal drift and spatial
      nonuniformity. In this paper, we present a novel approach based on single-image
      processing to simultaneously estimate temperature variances of FPAs and
      compensate the resulting temperature-dependent nonuniformity. Through well
      controlled thermal calibrations, empirical behavioral models are derived to
      characterize the relationship between the responses of microbolometer and FPA
      temperature variations. Then, under the assumption that strong dependency exists
      between spatially adjacent pixels, we estimate the optimal FPA temperature so as
      to minimize the global intensity variance across the entire thermal infrared
      image. We make use of the estimated FPA temperature to infer an appropriate
      nonuniformity correction (NUC) profile. The performance and robustness of the
      proposed temperature-adaptive NUC method are evaluated on realistic IR images
      obtained by a 640 * 512 pixels uncooled LWIR microbolometer imaging system
      operating in a significantly changed temperature environment.

PMID- 24085087
TI  - Stability of negative electron affinity Ga0.37Al0.63As photocathodes in an
      ultrahigh vacuum system.
AB  - The stability of negative electron affinity Ga0.37Al0.63As photocathodes in an
      ultrahigh vacuum system has been investigated. The degraded photocurrents of the
      Cs/O activated Ga0.37Al0.63As photocathodes under illumination with different
      intensity are recorded in real time, and the quantum efficiencies are measured
      after the degradation. The degraded quantum efficiencies of the photocathode
      under no illumination are measured at regular intervals. Multiple activations are
      performed on the Ga0.37Al0.63As photocathode, after that the quantum efficiencies
      and the degraded photocurrents are measured. The results indicate that the
      lifetime of the Ga0.37Al0.63As photocathode increases as the intensity of
      illumination decreases, and is longer than that of the GaAs photocathode in the
      case of no illumination. Besides, the Ga0.37Al0.63As photocathode performed after
      the second activation would obtain optimal stability.

PMID- 24085088
TI  - Flexible camera calibration using not-measured imperfect target.
AB  - A constrained optimization process is proposed for camera calibration with an
      imperfect and not-measured calibration target. The proposed method uses the
      geometry of the calibration target in an optimization process with constraints
      based on the pattern design statistically. As a result, the camera can be
      calibrated in the absolute scale without taking any measurement of the imperfect
      calibration target. It is verified through simulation and experiment that the
      reprojection errors by using the proposed method are obviously smaller than those
      of the traditional calibration approach by trusting an imperfect target. The
      slightly higher measurement precision is also exemplified through an experimental
      calibration of a stereo vision system. 

PMID- 24085089
TI  - Downwelling and upwelling radiance distributions sampled under cloudless
      conditions in Antarctica.
AB  - We have sampled both the downwelling and upwelling radiance distributions at a
      camp located in the southern Ellsworth Mountains on the broad expanse of Union
      Glacier (700 m altitude, 79 degrees  46' S, 82 degrees  52' W). The measurements
      (at 320-440 nm wavelength range) were carried out under cloudless conditions by
      using a sky scanner system, during a campaign (in December, 2012) meant to assess
      the effects of the high albedo on the radiance distribution. The angular
      variations observed in both the downwelling and upwelling radiance distributions
      increase with the wavelength. However, these variations were considerably greater
      in the case of the downwelling radiance than in the case of the upwelling
      radiance. Indeed, we found that downwelling radiance tends to be less isotropic
      than the corresponding upwelling radiance. Regardless of the solar zenith angle
      and the wavelength, the minima of the downwelling and the upwelling radiance
      distributions were measured close to the zenith and to the nadir, respectively.
      The downwelling (upwelling) radiance increased nearly monotonically toward the
      horizon and peaked at zenith (nadir) angles that ranged from 75 degrees  to 90
      degrees . Comparisons with the UVSPEC radiative transfer model were used to
      weight up the response of the downwelling radiance distribution to changes in the
      albedo.

PMID- 24085090
TI  - Enhancement effects of flat-mirror reflection on plasma radiation.
AB  - Laser-induced breakdown spectroscopy quality can be improved by using a
      nanosecond Nd:YAG laser pulse to excite soil samples. To investigate how flat
      mirror reflection affects the radiation characteristics of laser-induced plasma,
      emission spectra of sample elements were recorded using a grating spectrometer
      and photoelectric detection system. Placing a planar mirror vertically on the
      sample surface (10 mm mirror to plasma-center axis distance) for flat-mirror
      reflection increased spectral line intensities of Mg, Al, Fe, and Ba by 93.06%,
      159.63%, 93.43%, and 94.61%, respectively. Signal-to-noise ratio increased by
      17.56%, 40.21%, 31.29%, and 30%. The radiation enhancement mechanism was
      clarified using measured plasma parameters.

PMID- 24085091
TI  - Investigation of the chemical stability of the laser-induced fluorescence tracers
      acetone, diethylketone, and toluene under IC engine conditions using Raman
      spectroscopy.
AB  - This paper reports on an investigation of the chemical stability of the common
      laser-induced fluorescence (LIF) tracers acetone, diethylketone, and toluene.
      Stability is analyzed using linear Raman spectroscopy inside a heated pressure
      cell with optical access, which is used for the LIF calibration of these tracers.
      The measurements examine the influence of temperature, pressure, and residence
      time on tracer oxidation, which occurs without a rise in temperature or pressure
      inside the cell, highlighting the need for optical detection. A comparison
      between the three different tracers shows large differences, with diethylketone
      having the lowest and toluene by far the highest stability. An analysis of the
      sensitivity of the measurement shows that the detection limit of the oxidized
      tracer is well below 3% molar fraction, which is typical for LIF applications in
      combustion devices such as internal combustion (IC) engines. Furthermore, the
      effect on the LIF signal intensity is examined in an isothermal turbulent mixing
      study. 

PMID- 24085092
TI  - Multiple frequency bands of square split resonant rings and metal wire
      metamaterial.
AB  - This work presents experimental measurements of two square split resonant ring
      and metal wire (SSRR-MW) samples with different cell sizes at microwave
      frequencies. The geometrical sizes of the metamaterial cells are found to play an
      important role in the resonant frequency. Cells with different geometrical sizes
      are chosen to stack into a two-layer or three-layer metamaterial unit to realize
      the multiple negative passbands. The effective parameters of three separate SSRR
      MW models (a one-layer unit, a two-layer unit, and a three-layer unit) are
      retrieved from the simulation data. The composed models exhibit two or three
      negative bands by overlapping the passbands of original cells and broadening the
      overall bandwidth. The recovered parameters show good agreement with the
      theoretical analysis. 

PMID- 24085093
TI  - High-power PPMgLN-based optical parametric oscillator pumped by a linearly
      polarized, semi-fiber-coupled acousto-optic Q-switched fiber master oscillator
      power amplifier.
AB  - We have experimentally demonstrated a periodically poled magnesium-oxide-doped
      lithium niobate (PPMgLN)-based, fiber-laser-pumped optical parametric oscillator
      (OPO) generating idler wavelength of 3.82 MUm. The pump fiber laser was
      constructed with a linearly polarized, semi-fiber-coupled acousto-optic Q
      switched fiber oscillator and a polarization-maintaining fiber amplifier with
      pulse duration of 190 ns at the highest output power. The OPO was specifically
      configured in single-pass, singly resonant linear cavity structure to avoid the
      damage risk of the pump fiber laser, which is always a serious issue in the fiber
      laser-pumped, double-pass, singly oscillating structured OPOs. Under the highest
      pump power of 25 W, an idler average output power of 3.27 W with one-hour peak-to
      peak instability of 5.2% was obtained. The measured M2 factors were 1.98 and 1.44
      for horizontal and vertical axis, respectively. The high power stability and good
      beam quality demonstrated the suitability of such technology for practical
      application.

PMID- 24085094
TI  - Holographic grating stability: influence of 4,4'-azobis (4-cyanopentanoic acid)
      on various spatial frequencies.
AB  - This paper presents the results obtained when holographic gratings were stored
      with a spatial frequency of 954 and 2663 lines/mm in transmission geometry and
      4600 lines/mm in reflection geometry in a polyvinyl alcohol/acrylamide-based
      material. Photopolymers are materials that give good results at low frequencies,
      but their diffraction efficiency (DE) decreases at high frequencies. A chain
      transfer agent, 4,4'-azobis (4-cyanopentanoic acid) (ACPA) was incorporated in
      the material composition to improve spatial resolution. Furthermore, a curing
      process was applied to the stored gratings in order to maintain the DE stable
      over time. The DE and shrinkage for symmetric holographic transmission and
      reflection gratings were measured to evaluate their quality and quantify the
      improvement produced by ACPA.

PMID- 24085095
TI  - Orthogonal incidence method for efficient sunlight collection from asymmetric
      light couplers in tree-structured light guiding systems.
AB  - Directly transporting sunlight for use in indoor lighting applications is an
      efficient way to utilize solar energy. This study proposes a tree-structured
      light guiding system (TLGS) to collect sunlight and transport it for indoor
      illumination. The use of asymmetric light couplers in a TLGS increases the amount
      of accumulated sunlight. An analytic ray tracing model of the asymmetric coupler
      is proposed to present the angle and height distributions of the propagated rays.
      The cutoff angles were derived, and this cutoff condition was used to determine
      which rays are able to travel through the coupling region. In simulations, the
      couplers with coupling angles (theta(coup)) of 30 degrees  and 50 degrees  were
      conducted, and the large theta(coup) coupler provided high coupling efficiency
      (0.450). The orthogonal incidence method was adopted to increase coupling
      efficiency (0.646), and subsequently the amount of accumulated sunlight. The
      amount of accumulated sunlight in a TLGS was increased by 44%.

PMID- 24085096
TI  - Photonic bandgap Bragg fiber sensors for bending/displacement detection.
AB  - We demonstrate an amplitude-based bending/displacement sensor that uses a plastic
      photonic bandgap Bragg fiber with one end coated with a silver layer. The
      reflection intensity of the Bragg fiber is characterized in response to different
      displacements (or bending curvatures). We note that the Bragg reflector of the
      fiber acts as an efficient mode stripper for the wavelengths near the edge of the
      fiber bandgap, which makes the sensor extremely sensitive to bending or
      displacements at these wavelengths. Besides, by comparison of the Bragg fiber
      sensor to a sensor based on a standard multimode fiber with similar outer
      diameter and length, we find that the Bragg fiber sensor is more sensitive to
      bending due to the presence of a mode stripper in the form of a multilayer
      reflector. Experimental results show that the minimum detection limit of the
      Bragg fiber sensor can be as small as 3 MUm for displacement sensing.

PMID- 24085097
TI  - Maximum likelihood method for calibration of Mueller polarimeters in reflection
      configuration.
AB  - We address calibration of Mueller polarimeters in the presence of noise. We
      compare an extension of the eigenvalue calibration method (ECM) and a maximum
      likelihood (ML) method. The performances of these two calibration methods are
      investigated with numerical simulations and real experiments on a broadband
      infrared polarimeter. It is found that the ML method is superior to the extended
      ECM in terms of calibration precision and can be used at lower signal-to-noise
      ratio. 

PMID- 24085098
TI  - Interferometric vibration sensor using phase-generated carrier method.
AB  - An interferometric fiber-optic vibration sensing system using the phase-generated
      carrier (PGC) method is proposed and experimentally demonstrated. The sensing
      section consists of a Sagnac interferometer combined with a Mach-Zehnder
      interferometer, a length of sensing fiber is shared between the two
      interferometers. The PGC demodulation scheme is used to demodulate the time
      varying phase shifts induced by vibrations. Spatial information can be extracted
      from the demodulated results. A prototype sensing system with a 628 m long
      sensing fiber has been tested and a spatial resolution better than 12 m is
      successfully achieved.

PMID- 24085099
TI  - Active modulation of refractive index by stress in the terahertz frequency range.
AB  - Experimental tests are presented to investigate the stress effect on terahertz
      (THz) waves with a THz time-domain spectroscopy system. Through the Jones matrix
      method, an experimental principle is derived according to the experimental
      system. Experimental results indicate the linear relationship between a
      polytetrafluoroethylene refractive index and applied stress. The result can be
      applied to the active modulation of a refractive index or phase of a THz wave. 

PMID- 24085100
TI  - Pulsed airborne lidar measurements of atmospheric optical depth using the Oxygen
      A-band at 765 nm.
AB  - We report on an airborne demonstration of atmospheric oxygen optical depth
      measurements with an IPDA lidar using a fiber-based laser system and a photon
      counting detector. Accurate knowledge of atmospheric temperature and pressure is
      required for NASA's Active Sensing of CO2 Emissions over Nights, Days, and
      Seasons (ASCENDS) space mission, and climate modeling studies. The lidar uses a
      doubled erbium-doped fiber amplifier and single photon-counting detector to
      measure oxygen absorption at 765 nm. Our results show good agreement between the
      experimentally derived differential optical depth measurements with the
      theoretical predictions for aircraft altitudes from 3 to 13 km.

PMID- 24085101
TI  - Modulated zero-area solitary pulses: properties and applications.
AB  - This paper investigates a specific kind of solitary pulse, the modulated zero
      area (MZA) solitary pulse, when propagating within MgO photonic bandgap medium
      doped with silver nanoparticles (NPs). It will be shown that two coupled MZA
      pulses do propagate unattenuated within this medium but for a certain combination
      of the dipole moments and the density of the NPs. More important, and in contrast
      to the other kinds of solitary pulses, one of the two MZA pulses exhibits a
      slowing in its group velocity in comparison to the other one, depending on the
      amplitudes of the components of the dipole moments of the NPs that are in
      resonance with the two MZA pulses. With this particular feature, the system has
      the potential of working as an all-optical switch. 

PMID- 24085102
TI  - Lensless object scanning holography for two-dimensional mirror-like and diffuse
      reflective objects.
AB  - Recently proposed lensless object scanning holography (LOSH) [Opt. Express 20,
      9382 (2012)] is a fully lensless method capable of improving the image quality in
      digital Fourier holography applied to one-dimensional (1D) reflective objects and
      it involves a very simplified experimental setup. LOSH is based on the recording
      and digital postprocessing of a set of digital lensless Fourier transform
      holograms, which finally results in a synthetic image with improved resolution,
      field-of-view (FOV), signal-to-noise ratio (SNR), and depth of field. In this
      paper, LOSH is extended to the cases of two-dimensional (2D) mirror-like and 1D
      diffuse-based objects. For 2D mirror-like objects, the experimental results show
      an impressive image quality improvement over a factor of 3 in FOV, SNR, and
      resolution, as good as that obtained for the 1D case but in two dimensions. For
      1D diffuse-based objects, in general the speckle affects the image resolution,
      which will not be only a function of the aperture size. In this case, increasing
      the aperture produces a decrease of the speckle size. Moreover, due to the
      overlapping of speckles between successive images, different types of digital
      processing can be applied to obtain the final synthetic image: fully incoherent,
      fully coherent, and partially coherent. The last, arising from the incoherent sum
      of several independent sets of coherently added images, provides the best
      improvement in the resolution. Experimental results for both types of objects are
      presented.

PMID- 24085103
TI  - Very sensitive fiber Bragg grating accelerometer using transverse forces with an
      easy over-range protection and low cross axial sensitivity.
AB  - The first fiber Bragg grating (FBG) accelerometer using direct transverse forces
      is demonstrated by fixing the FBG by its two ends and placing a transversely
      moving inertial object at its middle. It is very sensitive because a lightly
      stretched FBG is more sensitive to transverse forces than axial forces. Its
      resonant frequency and static sensitivity are analyzed by the classic spring-mass
      theory, assuming the axial force changes little. The experiments show that the
      theory can be modified for cases where the assumption does not hold. The resonant
      frequency can be modified by a linear relationship experimentally achieved, and
      the static sensitivity by an alternative method proposed. The principles of the
      over-range protection and low cross axial sensitivity are achieved by limiting
      the movement of the FBG and were validated experimentally. The sensitivities
      1.333 and 0.634 nm/g were experimentally achieved by 5.29 and 2.83 gram inertial
      objects at 10 Hz from 0.1 to 0.4 g (g = 9.8 * m/s2), respectively, and their
      resonant frequencies were around 25 Hz. Their theoretical static sensitivities
      and resonant frequencies found by the modifications are 1.188 nm/g and 26.81 Hz
      for the 5.29 gram one and 0.784 nm/g and 29.04 Hz for the 2.83 gram one,
      respectively.

PMID- 24085104
TI  - Ultrasmooth surface polishing based on the hydrodynamic effect.
AB  - This study will examine the feasibility of applying the hydrodynamic effect to
      ultrasmooth surface polishing. Differing from conventional pad polishing,
      hydrodynamic effect polishing is noncontact, as the polishing wheel is floated on
      the workpiece under the hydrodynamic effect. The material removal mechanism and
      the removal contour are analyzed in detail. Dynamic pressure and shear stress
      distribution on the workpiece are numerically simulated in three dimensions under
      different clearances between the polishing wheel and the workpiece, showing that
      the dynamic pressure distribution and the magnitude of shear stress on the
      workpiece are greatly influenced by the clearance. It is clearly demonstrated
      from fixed-point polishing experiments that material removal rates and contours
      are determined by the combined action of dynamic pressure and shear stress. A
      material removal analytic model is presented with the hydrodynamic effect
      polishing method. Finally, a polishing experiment is conducted on a quartz glass
      and the plastic scratches, cracks, and bumpy structures on the initial surface
      are clearly removed. Moreover, the processed surface roughness is improved to
      0.145 nm rms, 0.116 nm Ra.

PMID- 24085105
TI  - Optical attenuation of plasmonic nanocomposites within photonic devices.
AB  - Plasmonic nanostructures enable microscopic optical manipulation such as light
      trapping in photonic devices. However, integration of embedded nanostructures
      into photonic devices has been limited by tractability of nanoscale and
      microscale descriptions in device architectures. This work uses a linear
      algebraic model to distinguish geometric optical responses of nanoparticles
      integrated into dielectric substrates interacting with macroscopic back
      reflectors from absorptive and nonlinear plasmonic effects. Measured
      transmission, reflection, and attenuation (losses) from ceramic and polymer
      composites supporting two- and three-dimensional distributions of gold
      nanoparticles, respectively, are predictable using the model. A unique
      equilateral display format correlates geometric optical behavior and attenuation
      to nanoparticle density and back-reflector opacity, allowing intuitive, visual
      specification of density and opacity necessary to obtain a particular optical
      performance. The model and display format are useful for facile design and
      integration of plasmonic nanostructures into photonic devices for light
      manipulation. 

PMID- 24085106
TI  - Tuning interactions between zeolite and supported metal by physical-sputtering to
      achieve higher catalytic performances.
AB  - To substitute for petroleum, Fischer-Tropsch synthesis (FTS) is an
      environmentally benign process to produce synthetic diesel (n-paraffin) from
      syngas. Industrially, the synthetic gasoline (iso-paraffin) can be produced with
      a FTS process followed by isomerization and hydrocracking processes over solid
      acid catalysts. Herein, we demonstrate a cobalt nano-catalyst synthesized by
      physical-sputtering method that the metallic cobalt nano-particles homogeneously
      disperse on the H-ZSM5 zeolite support with weak Metal-Support Interactions
      (MSI). This catalyst performed the high gasoline-range iso-paraffin productivity
      through the combined FTS, isomerization and hydrocracking reactions. The weak MSI
      results in the easy reducibility of the cobalt nano-particles; the high cobalt
      dispersion accelerates n-paraffin diffusion to the neighboring acidic sites on
      the H-ZSM5 support for isomerization and hydrocracking. Both factors guarantee
      its high CO conversion and iso-paraffin selectivity. This physical-sputtering
      technique to synthesize the supported metallic nano-catalyst is a promising way
      to solve the critical problems caused by strong MSI for various processes. 

PMID- 24085107
TI  - Enrichment of nanoparticles and bacteria using electroless and manual actuation
      modes of a bypass nanofluidic device.
AB  - Current efforts in nanofluidics aimed at detecting scarce molecules or particles
      are focused mainly on the development of electrokinetic-based devices. However,
      these techniques require either integrated or external electrodes, and a
      potential drop applied across a carrier fluid. One challenge is to develop a new
      generation of electroless passive devices involving a simple technological
      process and packaging without embedded electrodes for micro- and nanoparticles
      enrichment with a view to applications in biology such as the detection of viral
      agents or cancers biomarkers. This paper presents an innovative technique for
      particles handling and enrichment based exclusively on a pressure-driven silicon
      bypass nanofluidic device. The device is fabricated by standard silicon micro
      nanofabrication technology. The concentration operation was demonstrated and
      quantified according to two different actuation modes, which can also be combined
      to enhance the concentration factor further. The first, "symmetrical" mode
      involves a symmetric cross-flow effect that concentrates nanoparticles in a very
      small volume in a very local point of the device. The second mode, "asymmetrical"
      mode advantageously generates a streaming potential, giving rise to an
      Electroless Electropreconcentration (EL-EP). The concentration process can be
      maintained for several hours and concentration factors as high as ~200 have been
      obtained when both symmetrical and asymmetrical modes are coupled. Proof of
      concept for concentrating E. coli bacteria by the manual actuation of the EL-EP
      device is also demonstrated in this paper. Experiments demonstrate more than a 50
      fold increase in the concentration of E. coli bacteria in only ~40 s.

PMID- 24085108
TI  - Apoptotic markers in a prostate cancer cell line: effect of ellagic acid.
AB  - Ellagic acid (EA) inhibits cell growth and induces apoptosis in cultured cells;
      however, the precise molecular mechanism involved in EA-induced apoptosis in
      prostate cancer cells is unknown. The aim of the present study was to delineate
      possible apoptotic pathway(s) involved in the EA-mediated chemotherapeutic
      effects in the LNCaP human prostatic cancer cell line. EA produced anti
      proliferative effects through inhibition of rapamycin (mTOR) activation and a
      reduction in intracellular levels of beta-catenin. Moreover, we demonstrated that
      EA induced apoptosis via downregulation of the anti-apoptotic proteins, silent
      information regulator 1 (SIRT1), human antigen R (HuR) and heme oxygenase-1 (HO
      1). EA modulated the expression of apoptosis-inducing factor (AIF) resulting in a
      significant increase in reactive oxygen species (ROS) levels and the activation
      of caspase-3. Finally, we demonstrated that EA reduced both transforming growth
      factor-beta (TGF-beta) and interleukin-6 (IL-6) levels. EA treatment resulted in
      the increased expression of the tumor suppressor protein p21 and increased the
      percentage of apoptotic cells. In conclusion, the results suggest that EA
      treatment represents a new and highly effective strategy in reducing prostate
      cancer carcinogenesis.

PMID- 24085109
TI  - Clinical outcome of anatomic double-bundle ACL reconstruction and 3D CT model
      based validation of femoral socket aperture position.
AB  - PURPOSE: The purpose of this study was to evaluate the clinical results of
      anatomic double-bundle (DB) anterior cruciate ligament (ACL) reconstruction in
      which anatomic position of femoral socket apertures was validated using three
      dimensional (3D) computed tomography (CT) modelling. METHODS: Anatomic DB ACL
      reconstructions with hamstring autografts were performed in 34 patients. Two
      femoral sockets were created through a far anteromedial (AM) portal behind the
      lateral intercondylar ridge with the assistance of intraoperative 3D fluoroscopic
      navigation. Femoral tunnel aperture positioning was investigated postoperatively
      using 3D CT images in all patients. Clinical results were also evaluated
      subjectively and objectively at least up to 2 years. RESULTS: Measurement of the
      AM and the posterolateral (PL) femoral socket locations on the 3D CT images using
      the quadrant method showed that the centre of the AM socket aperture was located
      at a depth of 21.0 +/- 4.1% and a height of 30.5 +/- 9.3% and that of the PL
      socket aperture was located at a depth of 31.3 +/- 5.8% and a height of 57.2 +/-
      7.7%. The femoral socket locations were considered as anatomic in accordance with
      previous cadaveric studies examining the positions of ACL femoral insertion site.
      Subjectively, the mean Lysholm score was 96.9 +/- 4.0 points. According to IKDC
      final objective scores, 26 knees (76%) were objectively graded as normal, 8 (24%)
      as nearly normal, and 0 (0%) as abnormal or severely abnormal. Postoperative side
      to-side anterior translation measured with a KT-2000 arthrometer averaged 0.7 +/-
      1.2 mm. CONCLUSIONS: DB ACL reconstructions in which femoral socket apertures
      were validated anatomically using 3D CT provided satisfactory short-term results.
      LEVEL OF EVIDENCE: Case series, Level IV.

PMID- 24085110
TI  - The landscape of viral expression and host gene fusion and adaptation in human
      cancer.
AB  - Viruses cause 10-15% of all human cancers. Massively parallel sequencing has
      recently proved effective for uncovering novel viruses and virus-tumour
      associations, but this approach has not yet been applied to comprehensive patient
      cohorts. Here we screen a diverse landscape of human cancer, encompassing 4,433
      tumours and 19 cancer types, for known and novel expressed viruses based on >700
      billion transcriptome sequencing reads from The Cancer Genome Atlas Research
      Network. The resulting map confirms and extends current knowledge. We observe
      recurrent fusion events, including human papillomavirus insertions in RAD51B and
      ERBB2. Patterns of coadaptation between host and viral gene expression give clues
      to papillomavirus oncogene function. Importantly, our analysis argues strongly
      against viral aetiology in several cancers where this has frequently been
      proposed. We provide a virus-tumour map of unprecedented scale that constitutes a
      reference for future studies of tumour-associated viruses using transcriptome
      sequencing data. 

PMID- 24085112
TI  - Polynuclear copper(II) pyrazolate complexes: temperature-dependent protonolysis
      reactions, crystal structures and high catalytic activity toward the condensation
      of nitriles with 2-aminoalcohol.
AB  - Reaction of Cu(OAc)2.H2O and 1H-pyrazole-3,5-dicarboxylic acid dimethyl ester
      (Hdcmpz) in MeOH at room temperature afforded one tetranuclear Cu(II)/pyrazolate
      complex [{Cu2(MU-OAc)2}2(MU-dcmpz)2(MU-OAc)2] (1) in 89% yield. The similar
      reaction in refluxing MeOH produced a hexanuclear metallamacrocyclic
      Cu(II)/pyrazolate complex [{Cu(MU-dcmpz)}2(MU-OMe)2]3 (2) in 85% yield. Treatment
      of the same components under solvothermal conditions resulted in the formation of
      another tetranuclear Cu(II)/pyrazolate/carboxylate complex [{Cu(MeOH)}4(MU
      mcccpz)4] (3, Hmcccpz = 5(3)-(methoxycarbonyl)-1H-pyrazole-3(5)-carboxylic acid)
      in 30% yield. The mcccpz(2-) ion in 3 was in situ generated via the hydrolysis of
      one of two esters on dcmpz ligand. Complexes 1-3 were characterized by elemental
      analysis, IR and single-crystal X-ray diffraction. An X-ray analysis revealed
      that 1 contains two {Cu(MU-OAc)}2 fragments that are interconnected by two MU
      eta(2),eta(2)-dcmpz(-) ligands and two MU-eta(1),eta(1)-OAc(-) ions, forming a
      unique tetrameric structure. Complex 2 is composed of three {Cu(MU-dcmpz)}2
      fragments linked by three pairs of MU-OMe(-) anions, forming a metallamacrocyclic
      crown structure. 3 consists of four {Cu(MeOH)} fragments linked by two pairs of
      MU-eta(1),eta(2)-mcccpz(2-) ligands, forming a tetrameric [2 * 2] grid-like
      structure. Complexes 1-3 displayed high catalytic activity toward the
      condensation of nitriles with 2-aminoalcohol under solvent-free conditions to
      produce various 2-oxazolines.

PMID- 24085111
TI  - Potential therapeutic value of dendritic cells loaded with NY-ESO-1 protein for
      the immunotherapy of advanced hepatocellular carcinoma.
AB  - NY-ESO-1 is one of the most immunogenic cancer-testis (CT) antigens. Cancer
      vaccine trials based on NY-ESO-1 are currently ongoing. Dendritic cells (DCs) are
      the most potent antigen-presenting cells. The immune functions of DCs in a number
      of tumors have been identified; however, the potential therapeutic value of DCs
      pulsed with NY-ESO-1 in hepatocellular carcinoma (HCC) has not been extensively
      investigated. The objectives of the present study were to evaluate T cell
      response following stimulation with DCs pulsed with the recombinant NY-ESO-1
      protein (rESO) and to establish a correlation between NY-ESO-1 expression and
      clinicopathological features in HCC patients. DCs were generated with
      granulocyte/macrophage colony-stimulating factor (GM-CSF) and interleukin-4 (IL
      4) from human peripheral blood mononuclear cells. A mixed T cell reaction with
      DCs loaded with recombinant NY-ESO-1 protein (rESO-DCs) was evaluated by MTT
      assay. T cell responses against HCC cell lines were analyzed by measuring lactate
      dehydrogenase (LDH) activity. The protein levels of NY-ESO-1 were detected by
      immunohistochemistry (IHC) in a tissue microarray (TMA) containing 190 HCC
      samples. NY-ESO-1 transcript abundance was determined by reverse transcriptase
      polymerase chain reaction (RT-PCR) in 54 out of the 190 HCC samples. The results
      revealed that mature DCs were induced and that rESO-DCs significantly stimulated
      T cell proliferation. The specific lysis of T cells stimulated with rESO-DCs was
      significantly higher in the NY-ESO-1-positive HCC cells compared with the NY-ESO
      1-negative cells and the other controls (p<0.01). NY-ESO-1 was expressed in 15.8%
      (30/190)of the HCC samples, as shown by IHC and in 24.1% (13/54) of the samples,
      as shown by RT-PCR. The frequency of NY-ESO-1 expression was significantly higher
      in HCC patients with portal vein tumor thrombosis (24.6%) compared with those
      without thrombosis (11.2%, p=0.013). Our data suggest that DCs loaded with NY-ESO
      1 protein stimulate antigen-specific T cell responses against HCC cells in vitro.
      NY-ESO-1 may thus be used as a potential target for immunotherapy in advanced
      HCC. 

PMID- 24085113
TI  - Fibrinolytic treatment of ST-elevation myocardial infarction. Update 2014.
AB  - Primary percutaneous coronary intervention (PPCI) is the preferred reperfusion
      therapy in ST-elevation myocardial infarction (STEMI), as long as it can be
      delivered within 90-120 minutes from patient's first medical contact, and is the
      leading reperfusion strategy in most European countries. However, as PPCI cannot
      be offered in a timely manner to all patients, fibrinolytic therapy (FT) is the
      recommended choice in patients with an anticipated delay to PPCI of >90-120
      minutes, presenting early after symptom onset and without contra-indications. FT
      should preferably be started in the pre-hospital setting. Following FT, all
      patients should be transferred to a PCI-center for rescue PCI or routine coronary
      angiography with PCI as indicated. Such a pharmaco-invasive strategy, combining
      FT with invasive treatment, has recently been shown to be non-inferior to PPCI in
      patients living in areas with long transfer delays to PCI (>60 minutes). In this
      overview, we will briefly present the evidence for the benefit of FT in STEMI,
      and discuss the role of FT in the current era of PPCI as well as the optimal
      treatment following pharmacologic reperfusion. 

PMID- 24085114
TI  - In situ SEM study of a lithium deposition and dissolution mechanism in a bulk
      type solid-state cell with a Li2S-P2S5 solid electrolyte.
AB  - In situ SEM observation of a lithium deposition and dissolution process in an all
      solid-state lithium metal battery using a sulfide-based solid electrolyte (SE)
      was carried out. We revealed visually that the morphology of lithium deposition
      varies with the operating current densities. At current densities higher than 1
      mA cm(-2), local lithium deposition triggers large cracks, leading to a decrease
      in the reversibility of lithium deposition and dissolution. On the other hand, at
      a low current density of 0.01 mA cm(-2), its homogeneous deposition, which
      enables the reversible deposition and dissolution, hardly brings about the
      occurrence of unfavorable cracks. These results suggest that homogeneous lithium
      deposition on the SE and the suppression of the growth of lithium metal along the
      grain boundaries inside the SE are keys to achieve the repetitive lithium
      deposition and dissolution reaction without deterioration of the SE. 

PMID- 24085115
TI  - Effect of ascorbic acid and X-irradiation on HL-60 human leukemia cells: the
      kinetics of reactive oxygen species.
AB  - Ascorbic acid (AsA) treatment is expected to be a potential cancer therapy
      strategy with few side-effects that can be used alone or in combination with
      chemotherapy. However, the combination of AsA, a free radical scavenger, with
      radiation is not clearly understood; conflicting data are reported for cancer
      cell death. We conducted this study to determine the effect of AsA treatment
      combined with X-irradiation and the role of reactive oxygen species (ROS) in HL
      60 human promyelocytic leukemia cells. Additive cytotoxic effects were observed
      when the cells were exposed to 2 Gy X-irradiation after 2.5 mM AsA treatment.
      When catalase was added to the culture with AsA alone, the cytotoxic effects of
      AsA disappeared. X-irradiation increased intercellular ROS levels and
      mitochondrial superoxide levels. By contrast, AsA alone and in combination with X
      irradiation decreased ROS levels. However, in the presence of catalase
      neutralizing H2O2, AsA alone or in combination with X-irradiation only slightly
      decreased the intercellular ROS. Moreover, AsA decreased the mitochondrial
      membrane potential, which is commonly associated with apoptosis. These results
      suggest that the reduction of ROS did not result from ROS scavenging by AsA, and
      AsA induced apoptosis through a ROS-independent pathway. This study reports that
      a combination of AsA with radiation treatment is effective in cancer therapy when
      considering ROS in cancer cells.

PMID- 24085116
TI  - Tunable focusing of sine-azimuthal wavefront modulated cosh-Gaussian beams by one
      spiral optical vortex.
AB  - Optical intensity distributions in the focal region play an important role in
      many optical systems. In this paper, the tunable focusing properties of linearly
      polarized hyperbolic-cosine-Gaussian beams with sine-azimuthal variation
      wavefront were investigated by adding a spiral optical vortex. It was found that
      the focal patterns can be altered very considerably by changing the charge number
      of the optical vortex under a different phase parameter that indicates the phase
      change frequency upon increasing the azimuthal angle. The symmetry of focal
      patterns also changes remarkably upon increasing the charge number. And some
      novel focal patterns may appear, including a multiple-peak array, wheel focal
      pattern, or swallow-tailed focal pattern. 

PMID- 24085117
TI  - Dual-band electro-optic polarization switch based on dual-core liquid-crystal
      photonic crystal fibers.
AB  - Compact voltage-controlled all-in-fiber polarization switches are designed and
      investigated based on dual-core photonic crystal fibers, by selectively
      infiltrating one of the fiber's cores with a nematic liquid crystal. The electro
      optical control of the liquid crystal core's optical properties allows for the
      splitting of the two orthogonal polarizations, showing crosstalk values lower
      than -20 dB in a 40 nm window at 1550 nm, for an ultracompact length less than
      0.6 mm. With proper selection of the control voltage and the component length,
      dual-band operation with a crosstalk lower than -20 dB is also demonstrated for
      the 1300 and 1550 nm telecom bands.

PMID- 24085118
TI  - Measurement and analysis of water vapor inside optical components for optical
      fiber H2O sensing system.
AB  - Water vapor existing inside internal end-face gaps of optical components of an
      optical fiber H2O sensing system makes it possible to influence the measurement
      accuracy and stability. The influence principle has been briefly analyzed based
      on the structure of three main optical components: a distributed feedback laser
      diode (DFB-LD), a collimator, and a photoelectric diode (PD). With application of
      a differential technique, the influence of water vapor inside the DFB-LD can be
      removed. With reasonable recombination of the collimator and the PD in a dual
      beam detection system, the influence of water vapor inside the collimator and the
      PD's end-face gaps has been suppressed from more than 1.57*10(-3) to as low as 
      2.175*10(-5) in absorbance. After H2O isolation processing water vapor inside the
      end-face gaps of the DFB-LD, the collimator, and the PD can be utilized as a
      reference to design a simple but feasible H2O sensor. As a result, good linearity
      with an R2 of 0.9964 has been realized in a concentration range of 39-2110 ppm
      during an application test, and a long-term test of the designed H2O sensor
      against the S8000 with a difference of 10 ppm has been achieved.

PMID- 24085119
TI  - Feedback control of optical beam spatial profiles using thermal lensing.
AB  - A method for active control of the spatial profile of a laser beam using adaptive
      thermal lensing is described. A segmented electrical heater was used to generate
      thermal gradients across a transmissive optical element, resulting in a
      controllable thermal lens. The segmented heater also allows the generation of
      cylindrical lenses, and provides the capability to steer the beam in both
      horizontal and vertical planes. Using this device as an actuator, a feedback
      control loop was developed to stabilize the beam size and position. 

PMID- 24085120
TI  - Quality evaluation of spaceborne SiC mirrors (II): evaluation technology for
      mirror accuracy using actual measurement data of samples cut out from a mirror
      surface.
AB  - The authors studied the quality evaluation technology of a spaceborne large-scale
      lightweight mirror that was made of silicon carbide (SiC)-based material. To
      correlate the material property of a mirror body and the mirror accuracy, the
      authors evaluated the mirror surface deviation of a prototype mirror by inputting
      actually measured coefficient of thermal expansion (CTE) data into a finite
      element analysis model. The CTE data were obtained by thermodilatometry using a
      commercial grade thermal dilatometer for the samples cut from all over the mirror
      surface. The computationally simulated contour diagrams well reproduced the
      mirror accuracy profile that the actual mirror showed in cryogenic testing.
      Density data were also useful for evaluating the mirror surface deviation because
      they had a close relationship with the CTE. 

PMID- 24085121
TI  - Avoiding the side-effect of high-performance spectrometers with coded apertures.
AB  - In this report, a high-resolution, high-signal-to-noise-coded aperture
      spectrometer is introduced that replaces the traditional single slit with two
      dimensional array slits manufactured by microelectromechanic system technology.
      The encoding and decoding principle of this coded aperture spectrometer is
      described, as well as the instrument structure. We then discuss the side-effect,
      which is caused by sub-aperture manufacturing errors in size and position and the
      smear noise in the imaging CCD. The side-effect adversely affects the decoding
      wavelength accuracy of this spectrometer, so we present some effective ways to
      avoid this phenomenon and to increase the decoding wavelength accuracy of the
      spectrometer. In the end, we present our experimental results. 

PMID- 24085122
TI  - Fabrication of two kinds of eight-fold photonic quasi-crystals assisted by a
      specially designed prism.
AB  - We demonstrate that two kinds of 2D eight-fold photonic quasi-crystals (PQCs) can
      be fabricated by a specially designed prism via single-exposure holographic
      lithography. The prism with five continuous side surfaces out of common eight
      symmetrical side surfaces, plus a top surface, is well designed for PQC
      fabrication. Compared with the traditional method of setting up eight free-space
      beams in the half-space for an eight-fold PQC fabrication, our specially designed
      prism reduces the number of beams, avoids the differences of beam-to-beam phases,
      and simplifies the fabrication process. The theory and computer simulation
      confirm the patterns of two kinds of PQCs by a single prism illumination
      recording. Further, these quasi-crystal patterns are successfully verified by
      experimental results under a scanning electron microscope. In addition, these
      samples show some good properties, such as uniformity over large area, the
      implementation of a single defect by underexposure, and symmetry break of the
      eight dots. Our special prism-assisted holographic lithography technique provides
      a base for further investigating the optical properties of these novel
      structures. 

PMID- 24085123
TI  - Ultrasonic characterization of delamination in aeronautical composites using
      noncontact laser generation and detection.
AB  - The characterization of delamination in composite plates with ultrasonic waves
      generated and detected by lasers is presented. Composite materials have become
      one of the most important structural materials in the aviation industry because
      of their excellent mechanical properties, such as high specific stiffness and
      antifatigue. This paper reports a new application of the laser ultrasonic
      technique to perform nondestructive detection of carbon-fiber-reinforced plastic
      (CFRP) and continuous-fiber-reinforced ceramic matrix composites (CFCCs)
      containing artificial internal defects, based on propagation characteristic of
      ultrasonic waves generated by pulse laser with a wavelength of 1064 nm and pulse
      duration of 10 ns. A laser interferometer based on two-wave mixing is used to
      measure ultrasonic wave signals. The main advantage of this technique over
      conventional ultrasonic testing techniques is the ability to carry out detection
      without using coupling agents. The research results prove that the laser
      ultrasonic technique is effective for the detection of internal defects in both
      CFRP and CFCC composite components, which should promote and expand the
      application of the technique in the aviation industry.

PMID- 24085124
TI  - Extended scene Shack-Hartmann wavefront sensor algorithm: minimization of scene
      content dependent shift estimation errors.
AB  - An adaptive periodic-correlation (APC) algorithm was developed for use in
      extended-scene Shack-Hartmann wavefront sensors. It provides high accuracy even
      when the subimages in a frame captured by a Shack-Hartmann camera are not only
      shifted but also distorted relative to each other. Recently we found that the
      shift estimate error of the APC algorithm has a component that depends on the
      content of the extended scene. In this paper, we assess the amount of that error
      and propose a method to minimize it. 

PMID- 24085125
TI  - All-optical tunable slow light achievement in photonic crystal coupled-cavity
      waveguides.
AB  - In this paper, a tunable low power slow light photonic crystal device with a
      silicon-on-insulator platform is proposed based on the combination of an
      asymmetric defects coupled-cavity waveguide and the electromagnetically induced
      transparency (EIT) phenomenon. Modulating the refractive index of special regions
      in the suggested structure by the EIT phenomenon leads to a relatively wideband
      slow light device with adjustable group index in the same structure. Using this
      feature, a small and compact delay line is introduced that has many applications
      in optical telecommunications, especially in buffers. The numerical calculations
      show that the group index of 80-98 over the slow light bandwidth from 3.2 to 2.6
      nm is achievable for the central wavelength of 1546-1555 nm, respectively. The
      device malfunction, due to fabrication errors, is modeled, and the tunable
      characteristics of the proposed structure are verified.

PMID- 24085126
TI  - Fast and precise Laguerre-Gaussian beam steering with acousto-optic deflectors.
AB  - Novel fluorescence microscopy techniques and two-color laser direct imaging
      photolithography methods that enable resolution an order of magnitude beyond the
      diffraction limit require Laguerre-Gaussian beams and a fast and precise laser
      beam steering device to obtain images and produce microstructures. An acousto
      optic deflector (AOD) is a suitable choice and provides high-speed random access
      beam positioning with subnanometer precision as well as beam intensity control in
      a single element. In high-resolution applications, the impact of an AOD on beam
      quality plays a major role. We study the transfer function of an AOD for a
      fundamental Gaussian and a doughnut-shaped Laguerre-Gaussian beam by measuring
      the beam quality as a function of the diffraction angle after passing through the
      device. It is demonstrated that an AOD introduces negligible distortion and
      degradation to the beam profile and is therefore highly suitable for use in super
      resolution imaging and photolithography techniques where manipulation of Laguerre
      Gaussian doughnut-shaped beams is required. 

PMID- 24085127
TI  - Fourier domain optical tool normalization for quantitative parametric image
      reconstruction.
AB  - There has been much recent work in developing advanced optical metrology methods
      that use imaging optics for critical dimension measurements and defect detection.
      Sensitivity to nanometer-scale changes has been observed when measuring critical
      dimensions of subwavelength 20 nm features or when imaging defects below 15 nm
      using angle-resolved and focus-resolved optical data. However, these methods
      inherently involve complex imaging optics and analysis of complicated three
      dimensional electromagnetic fields. This paper develops a new approach to enable
      the rigorous analysis of three-dimensional, through-focus, or angle-resolved
      optical images. We use rigorous electromagnetic simulation with enhanced Fourier
      optical techniques, an approach to optical tool normalization, and statistical
      methods to evaluate sensitivities and uncertainties in the measurement of
      subwavelength three-dimensional structures.

PMID- 24085128
TI  - Transverse-electric and transverse-magnetic mode slow light propagation in a two
      dimensional photonic crystal waveguide.
AB  - A two-dimensional photonic crystal waveguide structure is designed for both TE-
      and TM-mode slow light propagation. The minimum group index of the waveguide for
      TE and TM modes can reach to 137.8 and 126.4, and the two polarizations have the
      same slow light frequency region. The designed structure can provide a large
      bandwidth range with very low group velocity dispersion for both TE and TM modes.
      The transmission property investigation for a suspended two-dimensional slab
      photonic crystal waveguide (PCW) indicates that such slow light character may be
      retained when perfect reflectors can be fixed on the horizontal surfaces of the
      slab. Such high group index for both TE and TM modes in two-dimensional PCWs is,
      to the best of our knowledge, first reported here, and may provide some useful
      guides for slow light research in theory. 

PMID- 24085129
TI  - Temperature dependence of anisotropic diffraction in holographic polymer
      dispersed liquid crystal memory.
AB  - Grating devices using photosensitive organic materials play an important role in
      the development of optical and optoelectronic systems. High diffraction
      efficiency and polarization dependence achieved in a holographic polymer
      dispersed liquid crystal (HPDLC) grating are expected to provide polarization
      controllable optical devices, such as a holographic memory for optically
      reconfigurable gate arrays (ORGAs). However, the optical property is affected by
      the thermal modulation around the transition temperature (T(ni)) where the liquid
      crystal (LC) changes from nematic to isotropic phases. The temperature dependence
      of the diffraction efficiency in HPDLC grating is investigated using four types
      of LC composites comprised of LCs and monomers having different physical
      properties such as T(ni) and anisotropic refractive indices. The holographic
      memory formed by the LC with low anisotropic refractive index and LC diacrylate
      monomer implements optical reconfiguration for ORGAs at a high temperature beyond
      T(ni) of LC.

PMID- 24085130
TI  - One-frame two-dimensional deflectometry for phase retrieval by addition of
      orthogonal fringe patterns.
AB  - Deflectometry is a well-known method to characterize pure phase objects by
      measuring the deformation of fringes. In principle, the retrieved magnitude is
      the partial derivative of the phase along the coordinate orthogonal to the
      fringes. In order to recover the phase it is necessary to know the derivatives in
      two orthogonal directions, which is usually achieved by rotating 90 degrees  the
      original fringes and acquiring a new deformed pattern. This "time-multiplexed"
      two-dimensional deflectometry is a time-consuming operation if the goal is to
      characterize phase objects in real time. In the present paper we propose a kind
      of two-dimensional deflectometry that allows acquisition of fringe patterns in
      two orthogonal directions in a single frame. The proposed procedure utilizes a
      two-dimensional ("additive") fringe pattern that allows the application of
      Takeda's method to each coordinate independently. The advantage of the method
      (with respect to the traditional one) is that it simplifies the setup and reduces
      the acquisition time. Validation experiments are presented. 

PMID- 24085131
TI  - Phase function design of a diffraction grating lens for an optical imaging system
      from a Fraunhofer diffraction perspective.
AB  - The potential exists to apply diffraction gratings to optical imaging systems to
      improve camera resolution and shorten optical length. However, we have noted the
      generation of striped flare lights, which differ from unnecessary-order
      diffraction lights, under intense lighting. We have elucidated the generation
      principle of these new striped lights and have discovered that they are caused by
      narrow diffraction grating rings. In this paper, using an analysis based on
      Fraunhofer diffraction, we suggest a way of minimizing them by designing an
      appropriate phase function structure, and test the efficacy of this design using
      our own manufactured prototype. 

PMID- 24085132
TI  - Quantifying phases in homogenous twisted birefringent medium.
AB  - The internal birefringence eta of an optical medium develops the dynamical phase
      through natural rotation of incident polarized light. The uniform twist of the
      medium induces an external birefringence in the system represented by k, the
      angular twist per unit thickness of the medium. This can be visualized through
      the geometric phase (GP) in association with internal birefringence. The
      representation of polarized photon, polarization matrix, and birefringent matrix
      are expressed in the l=1 orbital angular momentum (OAM) sphere where the
      corresponding GP is OAM dependent. 

PMID- 24085133
TI  - Helical wavefront and beam shape modulated by advanced liquid crystal q-plate
      fabricated via photoalignment and analyzed by Michelson's interference.
AB  - In this study, electrically tunable advanced liquid crystal q-plates (ALCQPs)
      that combine two q values in one device to generate optical vortex beams were
      fabricated using a photoalignment method that involves the use of azo dye, a
      surfactant alignment material. The electrically tunable ALCQP device could be
      modulated to control the shape and polarization of a circularly polarized
      Gaussian laser beam that propagated through the device. A Gaussian beam modulated
      by an ALCQP under suitable applied voltage showed a variation beam shape with
      helical wavefront, as demonstrated by Michelson's interference. This helical
      wavefront beam carries an orbital angular momentum and can be used in an optical
      tweezers system to trap, move, and rotate particles simultaneously. 

PMID- 24085134
TI  - Fast distributed large-pixel-count hologram computation using a GPU cluster.
AB  - Large-pixel-count holograms are one essential part for big size holographic three
      dimensional (3D) display, but the generation of such holograms is computationally
      demanding. In order to address this issue, we have built a graphics processing
      unit (GPU) cluster with 32.5 Tflop/s computing power and implemented distributed
      hologram computation on it with speed improvement techniques, such as shared
      memory on GPU, GPU level adaptive load balancing, and node level load
      distribution. Using these speed improvement techniques on the GPU cluster, we
      have achieved 71.4 times computation speed increase for 186M-pixel holograms.
      Furthermore, we have used the approaches of diffraction limits and subdivision of
      holograms to overcome the GPU memory limit in computing large-pixel-count
      holograms. 745M-pixel and 1.80G-pixel holograms were computed in 343 and 3326 s,
      respectively, for more than 2 million object points with RGB colors. Color 3D
      objects with 1.02M points were successfully reconstructed from 186M-pixel
      hologram computed in 8.82 s with all the above three speed improvement
      techniques. It is shown that distributed hologram computation using a GPU cluster
      is a promising approach to increase the computation speed of large-pixel-count
      holograms for large size holographic display.

PMID- 24085135
TI  - Phase shift estimation from variances of fringe pattern differences.
AB  - This paper presents a simple algorithm for estimating phase shifts from only
      three interferograms. In it, the fringe pattern differences are computed first in
      order to remove the background component, and then the variances and further the
      standard deviations (SDs) of fringe pattern differences are calculated. The phase
      shifts are estimated, by using the law of cosines, from a triangle whose lengths
      of sides are the SDs just calculated. This algorithm offers several advantages
      over others, e.g., being efficient, easy to implement, accurate, and less
      sensitive to noise. Numerical simulations and an experiment are performed to
      demonstrate its validity. 

PMID- 24085136
TI  - Evaluation of subsurface damage by light scattering techniques.
AB  - Subsurface damage (SSD) in optical components is almost unavoidably caused by
      mechanical forces involved during grinding and polishing and can be a limiting
      factor, in particular for applications that require high laser powers or an
      extreme material strength. In this paper, we report on the characterization of
      SSD in ground and polished optical surfaces, using different light scattering
      measurement techniques in the visible and extreme ultraviolet spectral ranges.
      The materials investigated include fused silica, borosilicate glass, and calcium
      fluoride. The scattering results are directly linked to classical destructive SSD
      characterization techniques, based on white light interferometry, optical
      microscopy, and atomic force microscopy of the substrate topography and cross
      sections obtained after etching in hydrofluoric acid and fracturing. 

PMID- 24085137
TI  - Probe alignment and design issues of microelectromechanical system based optical
      coherence tomography endoscopic imaging.
AB  - Endoscopic optical coherence tomography (OCT) imaging has been demonstrated using
      microelectromechanical system (MEMS) technology by several research groups. The
      focus of this work is to study how the OCT imaging performance is affected by the
      radius of curvature of MEMS mirrors as well as the optical alignment accuracy
      inside small imaging probes. The goal of this study is to provide guidance for
      assembly tolerance and design optimization of OCT endoscopic probes. Gaussian
      beam propagation is used for theoretical analysis which is confirmed by optical
      simulation and verified experimentally with a time-domain OCT system as well. It
      has been found that the OCT imaging is very sensitive to the distance from the
      fiber end to the gradient-index (GRIN) lens, which needs to be controlled within
      0.1 mm to achieve working distance (WD) longer than 3.5 mm and lateral resolution
      around 25 MUm. The impact on image quality of the MEMS mirror is negligible if
      the radius of curvature of the mirror surface is greater than 200 mm. In
      addition, we studied the astigmatism introduced by cylindrical plastic tubing;
      the maximum astigmatism ratio is 1.1 when the WD is around 2.5 mm.

PMID- 24085138
TI  - Magneto-optics of nanoscale Bi:YIG films.
AB  - Magnetic circular dichroism in the spectral region from 270 to 850 nm and Faraday
      rotation at the wavelength of 655 nm in ultrathin (1.5-92.8 nm) films prepared by
      reactive ion beam sputtering of target of nominal composition Bi2.8Y0.2Fe5O12
      were studied. The observed effects of the "blue shift," inversion of the signs
      and change in the intensity of magneto-optical transitions, are discussed. It is
      demonstrated that all studied nanoscale films reveal magnetic properties-and
      their composition depends on the method of substrate surface pretreatment.

PMID- 24085139
TI  - Five-degrees-of-freedom measurement system based on a monolithic prism and phase
      sensitive detection technique.
AB  - This paper presents a method for measuring five-degrees-of-freedom errors of a
      moving stage with a monolithic prism and phase-sensitive detection technique. It
      consists of a pigtailed laser diode, three position-sensitive detectors (PSDs), a
      monolithic prism, and additional optical and electronic components. The
      monolithic prism mounted on the moving stage generates three beams that are
      detected by three PSDs, respectively, so that the straightness, pitch, yaw, and
      roll errors can be simultaneously measured. Theoretical analysis of each error
      measurement process is presented. To reduce the influence of disturbing light,
      the laser diode is modulated by a sinusoidal wave current, and a phase-sensitive
      detection technique is developed to demodulate the signals. Compared with a laser
      interferometer, the deviation errors when measuring the horizontal and vertical
      straightness errors are better than +/-0.25 and +/-0.4 MUm, respectively. The
      deviation errors for the pitch, yaw, and roll are better than +/-0.5, +/-0.3, and
      +/-2 arc sec, respectively, in comparison with an autocollimator. The system can
      be assembled to measure five error components of machine tools in an industrial
      environment.

PMID- 24085140
TI  - Multiwavelength generation based on a mode-locked fiber laser using carbon
      nanotube and fiber Fabry-Perot filter.
AB  - In this paper, a novel and compact configuration of stable multiwavelength
      generation with a uniform wavelength interval is proposed for the first time to
      our knowledge. It employs a mode-locked fiber laser using a carbon nanotube and
      spectrum-slicing technique. A flat rectangular optical output spectrum is
      demonstrated by adjusting the dispersion value of the fiber-loop cavity and the
      pump power. With a fiber Fabry-Perot filter, 33 wavelengths with 0.2 nm spacing
      are obtained among the power uniformity of 2.3 dB. Moreover, the variations of
      output power at each wavelength are all less than 0.1 dB, which implies excellent
      stability of the whole structure.

PMID- 24085141
TI  - Transmission and reflection characteristics of metal-coated optical fiber tip
      pairs.
AB  - The optical transmission and reflection in between two metalized optical fiber
      tips is studied in the optical near-field and far-field domains. In addition to
      aluminum-coated tips for near-field scanning optical microscopy (NSOM),
      specifically developed gold-coated fiber tips cut by focused ion beam are
      investigated. Transverse transmission maps of subwavelength width clearly
      indicate optical near-field coupling between the tips for short tip distances and
      become essentially Gaussian-shaped for larger distances in the far-field regime.
      Moreover, concentric reflection fringes observed for NSOM-type tips illustrate
      the influence of the receiving fiber tip on the emission pattern of the source
      tip. 

PMID- 24085142
TI  - Teaching and learning in urogynecology.
AB  - This paper was delivered as the Ulf Ulmsten Memorial Lecture in Brisbane, QLD,
      Australia, in 2012. It emphasises how urogynaecology as a young specialty needs
      to learn some lessons from its forebears as to how new knowledge should be
      analysed and incorporated into practice. The paper highlights the value of
      mentorship and teamwork and the need to be aware of increasing patient
      expectations. 

PMID- 24085143
TI  - Impact of levator trauma on pelvic floor muscle function.
AB  - INTRODUCTION AND HYPOTHESIS: Levator trauma is common after vaginal delivery,
      either as macrotrauma, i.e., levator avulsion, or microtrauma, i.e., irreversible
      overdistension of the levator hiatus. The effect of microtrauma on muscle
      function is unknown. We tested the hypothesis that levator trauma is associated
      with reduced contractile function of the levator ani. METHODS: Pregnant
      nulliparous women were recruited and seen before and after childbirth. All
      underwent an interview, a clinical examination including pelvic floor muscle
      (PFM) assessment using the Modified Oxford scale (MOS) [as an optional component]
      and translabial ultrasound. Sonographic and clinical parameters of PFM function
      were assessed before and after childbirth. RESULTS: Out of 560 women, 446
      returned at a median of 5 months after childbirth and 433 were suitable for
      analysis. There was a significant reduction in all measures of PFM function
      except for MOS. Change in MOS was associated with delivery mode [analysis of
      variance (ANOVA) P = 0.006). Forty-seven (15 %) vaginally parous women were
      diagnosed with levator avulsion, which was associated with a reduction in PFM
      contractility on sonographic parameters and MOS. However, only clinical
      assessment reached statistical significance. Sixty-five of 312 (21 %) women were
      diagnosed with microtrauma. We found no evidence of impairment in PFM
      contractility on ultrasound, but there was a statistically significant reduction
      in MOS. CONCLUSIONS: Both levator avulsion (macrotrauma) and irreversible
      overdistension (microtrauma) are associated with reduced contractile function.
      This effect is more easily detected by palpation than by sonographic indices of
      levator function.

PMID- 24085144
TI  - Short-term surgical outcomes and characteristics of patients with mesh
      complications from pelvic organ prolapse and stress urinary incontinence surgery.
AB  - INTRODUCTION AND HYPOTHESIS: Surgical treatment of pelvic organ prolapse (POP)
      and stress urinary incontinence (SUI) can include the use of synthetic materials.
      Placement of synthetic materials into the vaginal wall, through either the vagina
      or the abdomen, includes the risk of complications such as vaginal wall extrusion
      or pain. There is little data regarding outcomes following treatment of mesh
      complications. METHODS: A retrospective chart review of patients who underwent
      excision of mesh placed for POP or SUI between 1 January 2001 and 31 October 2012
      was performed at the University of Virginia. Chart abstraction queried patient
      demographics, clinical history, physical examination, pre- and post-excision
      symptoms, and operative findings. The International Continence Society (ICS) and
      International Urogynecological Association (IUGA) classification system was used
      to define the nature and location of mesh complications. RESULTS: A total of 57
      patients (26 mid-urethral slings, 23 transvaginal prolapse, 9 intraperitoneal
      prolapse) with the diagnosis of mesh extrusion into the vaginal wall were
      analyzed. Twenty-five (average 2.8 cases/year) original mesh surgeries occurred
      between January 2001 and January 2010 and 41 (average 20.5 cases/year) occurred
      after January 2010. The most common presenting patient complaints were chronic
      pelvic pain (55.9 %), dyspareunia (54.4 %), and vaginal discharge (30.9 %). At a
      6-week post-operative visit, 57.3 % of patient's symptoms were completely
      resolved and 14.6 % were improved. CONCLUSION: Clinicians should be cognizant of
      the variable presentations of post-operative vaginal mesh complications. Mesh
      excision by experienced pelvic surgeons is an effective and safe treatment for
      these complications; however, a significant number of patients may have
      persistent symptoms following surgery.

PMID- 24085145
TI  - Chronic vaginal discharge and left leg edema after a transobturator tape
      procedure.
AB  - We report on a patient who underwent total vaginal hysterectomy for urinary
      incontinence 8 years previously with a sling operation using transobturator tape
      (TOT). She was admitted to our hospital after complaints of vaginal discharge,
      foul odor, and bleeding, left thigh pain, and edema. Magnetic resonance imaging
      (MRI) and computed tomography (CT) revealed a fistula tract from the vagina or
      urethra with remnant sling tape. We removed the remnant tape using intraoperative
      ultrasonography. This case exemplifies the rare occurrence of a vaginal fistula
      extending to the obturator, adductor, and pectineus muscles combined with
      myositis after TOT placement. It is important that urogynecologists recognize
      that TOT procedures may result in complications accompanied by common recurrent
      vaginal symptoms, such as vaginal odor and spotting, which can be identified by
      MRI or CT.

PMID- 24085146
TI  - Risk factors for urinary incontinence 1 year after the first vaginal delivery in
      a cohort of primiparous Danish women.
AB  - INTRODUCTION AND HYPOTHESIS: The objective was to examine the relationship
      between maternal and perinatal factors and the occurrence of stress (SUI) or
      mixed (MUI) urinary incontinence (UI) 1 year after the first vaginal delivery in
      primiparous women. METHODS: Participants in this prospective cohort were
      recruited consecutively from June 2003 to July 2005 from all eligible women who
      delivered in the department. A validated questionnaire, the International
      Consultation of Incontinence Questionnaire Short Form (ICIQ-SF) was completed by
      all participants 2-3 days after delivery, and a similar second questionnaire was
      filled out 1 year later. Additional data were obtained from the medical records.
      The first questionnaire was completed by 1,018 women (63 %) and the second by 859
      women (84 %). The study group comprised the 575 women without any UI before the
      pregnancy and who had a vaginal delivery. The primary analysis comprised 117
      women with either SUI or MUI 1 year after the vaginal delivery and 403 women
      without any UI. RESULTS: In univariate analyses, the following factors were
      associated with SUI or MUI: prepregnancy body mass index (BMI) >= 30 (p < 0.05),
      UI during the pregnancy (p < 0.05), perineal lesions (p < 0.05), and anal
      sphincter tears (p = 0.05). Logistic regression analysis showed that SUI or MUI
      was strongly associated with UI during the pregnancy [adjusted odds ratio (OR)
      4.7, 95 % confidence interval (CI) 2.9-7.7) and inversely associated with
      oxytocin augmentation (adjusted OR 0.5, 95 % CI 0.3-0.9). CONCLUSIONS: SUI or MUI
      1 year after the first vaginal delivery was strongly associated with UI during
      the pregnancy and inversely associated with oxytocin augmentation.

PMID- 24085147
TI  - Photophysical study of spiro-bifluorene bridged Pt(II), Os(II) and Ir(III)
      luminescent complexes and supramolecular arrays.
AB  - This paper describes expeditious stepwise synthesis of polynuclear complexes
      based on heteroleptic iridium(iii) and osmium(ii) fragments linked to a central
      Pt(ii) module via a spirobifluorene-bridge using a strategy based on the
      construction of preformed complexes. The luminescence features of the final multi
      chromophoric array, i.e. a tetrad consisting of spirobifluorene-bridged Pt, Ir
      and Os complexes, have been studied by comparison with the features of reference
      complexes bearing two identical luminophores (Ir or Os) at the periphery. The
      (3)MPtLCT and (3)LC states of the Pt and spiro ligand undergo fast energy
      transfer into the (3)MIrLCT or the (3)MOsLCT state in the Pt-M2 (M = Ir or Os)
      arrays, whereas the (3)LC and the (3)MPtLCT states function as energy reservoirs
      for the metal excited states close in energy, resulting in a pronounced increase
      of the excited state lifetimes of these arrays. The tetrad efficiently works as
      an antenna system where the collected light energy is transferred to the Os unit
      acting as the final collector. 

PMID- 24085148
TI  - Letter regarding article by Wang et al., "Internal fixation of distal
      tibiofibular syndesmotic injuries: a systematic review with meta-analysis".

PMID- 24085149
TI  - Comment on Zhou et al.: Do we really need closed-suction drainage in total hip
      arthroplasty? A meta-analysis.

PMID- 24085150
TI  - Experimental detection of transverse particle movement with structured light.
AB  - One procedure widely used to detect the velocity of a moving object is by using
      the Doppler effect. This is the perceived change in frequency of a wave caused by
      the relative motion between the emitter and the detector, or between the detector
      and a reflecting target. The relative movement, in turn, generates a time-varying
      phase which translates into the detected frequency shift. The classical
      longitudinal Doppler effect is sensitive only to the velocity of the target along
      the line-of-sight between the emitter and the detector (longitudinal velocity),
      since any transverse velocity generates no frequency shift. This makes the
      transverse velocity undetectable in the classical scheme. Although there exists a
      relativistic transverse Doppler effect, it gives values that are too small for
      the typical velocities involved in most laser remote sensing applications. Here
      we experimentally demonstrate a novel way to detect transverse velocities. The
      key concept is the use of structured light beams. These beams are unique in the
      sense that their phases can be engineered such that each point in its transverse
      plane has an associated phase value. When a particle moves across the beam, the
      reflected light will carry information about the particle's movement through the
      variation of the phase of the light that reaches the detector, producing a
      frequency shift associated with the movement of the particle in the transverse
      plane. 

PMID- 24085153
TI  - Depression and the risk of cancer: a 15-year follow-up study of the GAZEL cohort.
AB  - Depression has long been hypothesized to be associated with cancer incidence.
      However, there is evidence for a positive publication bias in this field. In the
      present study, we examined the association between various measures of depression
      and cancer incidence at several sites. A total of 14,203 members of the French
      GAZEL (Gaz et Electricite) cohort (10,506 men, 3,697 women) were followed up for
      diagnoses of primary cancers from January 1, 1994, to December 31, 2009. All
      medically certified sickness absences for depression recorded between January 1,
      1990, and December 31, 1993, were compiled. Depressive symptoms were self
      reported in 1993, 1996, and 1999 with the Center for Epidemiologic Studies
      Depression Scale. During a mean follow-up period of 15.2 years, 1,119
      participants received a cancer diagnosis, excluding nonmelanoma skin cancer and
      in situ neoplasms. Considering 6 cancer sites (prostate, breast, colorectal,
      smoking-related, lymphoid and hematopoietic tissues, other sites) and 4 measures
      of depression, we found 1 positive association and 1 negative association.
      Overall, there was no compelling evidence for an association between depression
      and cancer incidence. Such null results should be considered when addressing
      concerns of cancer patients and their relatives about the role of depression in
      cancer onset. 

PMID- 24085151
TI  - Gender-dependent effects of gonadectomy on lung carcinogenesis by 4
      (methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK) in female and male A/J mice.
AB  - The present study was conducted to investigate the effects of gonadectomy on lung
      carcinogenesis in female and male mice, and to determine an association between
      sex hormone and lung carcinogenesis. Female and male A/J mice were divided into
      gonadectomized and unoperated control groups and all animals were treated
      intraperitoneally with 1 or 2 injections of 4-(methylnitrosamino)-1-(3-pyridyl)-1
      butanone (NNK) at the dose of 2 mg/mouse. The mice were sacrificed 18 or 56 weeks
      after surgery. Serum levels of estradiol in females and testosterone in males
      were confirmed to be decreased by gonadectomy. Lung white nodules were detected
      in all mice of all groups. In the control groups of 18- and 56-week studies, the
      multiplicities of lung nodules in females were significantly greater than in
      males. In males in the 56-week study, the multiplicity of macroscopical lung
      nodules, bronchiolo-alveolar hyperplasias, adenomas and tumors (adenomas and
      adenocarcinomas) showed significant increase with castration. In females in the
      18-week study, the multiplicity of adenomas decreased significantly by
      ovariectomy. Based on the results of the present study, female A/J mice were
      confirmed to be more susceptible to NNK-induced lung carcinogenesis than males.
      Furthermore, it was suggested that the process is inhibited by testosterone and
      accelerated by estradiol. These findings indicate the possibility that sex
      hormones play important roles in determining sex differences in lung
      carcinogenesis in the A/J mice initiated by NNK.

PMID- 24085154
TI  - Effects of electroacupuncture on apoptotic pathways in a rat model of focal
      cerebral ischemia.
AB  - In this study, we investigated the molecular mechanisms underlying the anti
      apoptotic properties of electroacupuncture (EA) in a rat model of middle cerebral
      artery occlusion (MCAO). Treatment with 2 Hz EA (1 mA) resulted in a markedly
      reduced infarct area after stroke, particularly in the middle region of the
      brain. Treatment with EA resulted in a significant decrease in the number of
      apoptotic cells identified by Hoechst 33342 and TUNEL staining. According to the
      results of the analysis for proteins involved in apoptosis, treatment with EA
      resulted in a significantly reduced expression of death receptor (DR)5. Among the
      members of the Bcl-2 family, a higher expression of anti-apoptotic Bcl-2 and Bcl
      xL was observed in the rats treated with EA, compared with the untreated rats
      with MCAO. As regards the expression of the inhibitor of apoptosis protein (IAP)
      family, a higher expression of anti-apoptotic cIAP-1 and -2 was also detected in
      the cortex of the EA-treated rats. Using western blot analysis, we observed that
      activated caspase-3 was only significantly arrested by EA treatment in the rats
      with MCAO; however, according to the results of the caspase assay, the activities
      of caspase-3, -8 and -9 were markedly inhibited by EA treatment. These results
      suggest that treatment with EA exerts anti-apoptotic effects in cerebral ischemia
      in a rat model of MCAO and that these effects are associated with the inhibition
      of the DR and mitochondrial apoptotic pathways. 

PMID- 24085155
TI  - Riverscape and groundwater preservation: a choice experiment.
AB  - This study presents a quantitative approach to support policy decision making for
      the preservation of riverscapes, taking into account the EC Water Framework
      Directive (2000/60/EC) and the EC Nitrates Directive (91/676/EEC) concerning the
      protection of waters against nitrate pollution from agricultural sources. A
      choice experiment was applied to evaluate the benefits, as perceived by
      inhabitants, of the implementation of policies aiming to reduce the concentration
      of nitrates in groundwater, preserve the riverscape by maintaining a minimum
      water flow and increasing hedges and woods along the Serio River in central
      northern Italy. Findings suggested that people were particularly concerned about
      groundwater quality, probably because it is strongly linked to human health.
      Nevertheless, it was interesting to observe that people expressed a high
      willingness to pay for actions that affect the riverscape as a whole (such as the
      minimum water flow maintenance plus reforestation). This is probably due to the
      close connection between the riverscape and the functions of the river area for
      recreation, health purposes, and biodiversity preservation. 

PMID- 24085156
TI  - Structural kinetics of a Pt/C cathode catalyst with practical catalyst loading in
      an MEA for PEFC operating conditions studied by in situ time-resolved XAFS.
AB  - The structural kinetics of surface events on a Pt/C cathode catalyst in a
      membrane electrode assembly (MEA) with a practical catalyst loading (0.5 mgPt cm(
      2)) for a polymer electrolyte fuel cell were investigated by in situ time
      resolved X-ray absorption fine structure analysis (XAFS; time resolution: 100 ms)
      for the first time. The rate constants of structural changes in the Pt/C cathode
      catalyst in the MEA during voltage cycling were successfully estimated. For
      voltage-cycling processes, all reactions (electrochemical reactions and
      structural changes in the Pt catalyst) in the MEA were found to be much faster
      than those in an MEA with a thick cathode catalyst layer, but the in situ time
      resolved XAFS analysis revealed that significant time lags similarly existed
      between the electrochemical reactions and the structural changes in the Pt
      cathode catalyst. The time-resolved XAFS also revealed differences in the
      structural kinetics of the Pt/C cathode catalyst for the voltage-cycling
      processes under N2 and air flows at the cathode. 

PMID- 24085157
TI  - Molecular electrostatics for probing lone pair-pi interactions.
AB  - An electrostatics-based approach has been proposed for probing the weak
      interactions between lone pair containing molecules and pi deficient molecular
      systems. For electron-rich molecules, the negative minima in molecular
      electrostatic potential (MESP) topography give the location of electron
      localization and the MESP value at the minimum (Vmin) quantifies the electron
      rich character of that region. Interactive behavior of a lone pair bearing
      molecule with electron deficient pi-systems, such as hexafluorobenzene, 1,3,5
      trinitrobenzene, 2,4,6-trifluoro-1,3,5-triazine and 1,2,4,5-tetracyanobenzene
      explored within DFT brings out good correlation of the lone pair-pi interaction
      energy (E(int)) with the Vmin value of the electron-rich system. Such interaction
      is found to be portrayed well with the Electrostatic Potential for Intermolecular
      Complexation (EPIC) model. On the basis of the precise location of MESP minimum,
      a prediction for the orientation of a lone pair bearing molecule with an electron
      deficient pi-system is possible in the majority of the cases studied.

PMID- 24085158
TI  - Persistent enhanced platelet activation in patients with acute myocardial
      infarction and coronary microvascular obstruction: clinical implications.
AB  - About 30% of patients with acute ST-segment elevation myocardial infarction
      (STEMI) undergoing recanalisation of the infarct-related coronary artery do not
      achieve valid myocardial reperfusion (no-reflow phenomenon or coronary
      microvascular obstruction [MVO]). The mechanisms of MVO are incompletely
      understood. In this study we investigated the role platelet activation in the
      pathogenesis of coronary MVO in STEMI patients. We enrolled 48 STEMI patients
      (age 56.2 +/- 11 years; 31 men), treated by primary percutaneous coronary
      intervention (PCI) followed by double anti-platelet treatment, and 20 control
      patients with stable coronary artery disease (CAD) on single anti-platelet
      treatment (age 57.5 +/- 6 years, 12 men). STEMI patients were divided into two
      groups: 35 patients with complete myocardial reperfusion (MR) and 13 patients
      with coronary MVO despite successful PCI. Platelet activation was assessed on
      admission and at one-month follow-up by measuring platelet receptor expression
      and monocyte-platelet aggregates (MPAs). Platelet receptor expression, platelet
      receptor conformational change for fibrinogen binding availability and MPA
      formation were increased in STEMI patients with MVO compared to both STEMI
      patients with MR and stable CAD patients, both on admission and at one-month
      follow-up (p<0.05 for all).Among STEMI patients, platelet activation is greater
      in those who display coronary MVO, compared to those with MR, after successful
      PCI, both on admission and one month after STEMI, suggesting that enhanced
      platelet activation might be involved in the pathogenesis of MVO. The persistence
      of enhanced platelet activation despite double classical anti-platelet therapy
      suggests that new anti-platelet strategies should be considered in patients with
      coronary MVO. 

PMID- 24085159
TI  - Thermal response of a dental tissue induced by femtosecond laser pulses.
AB  - This paper reports a theoretical and experimental study for thermal transport in
      a thin slice of human tooth induced by a 120 fs, 800 nm pulse laser at a
      repetition rate of 1 kHz. The surface reflectivity of enamel and the convection
      heat transfer coefficient were determined using an inverse heat transfer
      analysis. Instead of a fully three-dimensional modeling, two simplified two
      dimensional (2D) planar and axisymmetric heat conduction models were proposed to
      simulate the temperature fields. The temperature responses obtained from the 2D
      planar and axisymmetric model agree well with the experimental measurements. On
      the other hand, the one-dimensional (1D) result significantly differs from the 2D
      axisymmetric one, suggesting that care should be taken when a 1D thermal model is
      considered for estimating temperature response. 

PMID- 24085160
TI  - On the performance of the physicality-constrained maximum-likelihood estimation
      of Stokes vector.
AB  - We address the estimation of the Stokes vectors taking into account the physical
      realizability constraint. We propose a fast method for computing the constrained
      maximum-likelihood (CML) estimator for any measurement matrix, and we compare its
      performance with the classical empirical physicality-constrained estimator. We
      show that when the measurement matrix is based on four polarization states
      spanning a regular tetrahedron on the Poincare sphere, the two estimators are
      very similar, but the CML provides a better estimation of the intensity. For an
      arbitrary measurement matrix, the CML estimator does not always yield better
      estimation performance than the empirical one: their comparative performances
      depend on the measurement matrix, the actual Stokes vector and the signal-to
      noise ratio. 

PMID- 24085161
TI  - Error analysis of compensation cutting technique for wavefront error of KH2PO4
      crystal.
AB  - Considering the wavefront error of KH(2)PO(4) (KDP) crystal is difficult to
      control through face fly cutting process because of surface shape deformation
      during vacuum suction, an error compensation technique based on a spiral turning
      method is put forward. An in situ measurement device is applied to measure the
      deformed surface shape after vacuum suction, and the initial surface figure
      error, which is obtained off-line, is added to the in situ surface shape to
      obtain the final surface figure to be compensated. Then a three-axis servo
      technique is utilized to cut the final surface shape. In traditional cutting
      processes, in addition to common error sources such as the error in the
      straightness of guide ways, spindle rotation error, and error caused by ambient
      environment variance, three other errors, the in situ measurement error, position
      deviation error, and servo-following error, are the main sources affecting
      compensation accuracy. This paper discusses the effect of these three errors on
      compensation accuracy and provides strategies to improve the final surface
      quality. Experimental verification was carried out on one piece of KDP crystal
      with the size of Phi270 mm*11 mm. After one compensation process, the peak-to
      valley value of the transmitted wavefront error dropped from 1.9lambda
      (lambda=632.8 nm) to approximately 1/3lambda, and the mid-spatial-frequency error
      does not become worse when the frequency of the cutting tool trajectory is
      controlled by use of a low-pass filter.

PMID- 24085162
TI  - Formation of optical vortices through superposition of two Gaussian beams.
AB  - We observe phase singularities in the superposed field of two Gaussian beams. It
      is seen that the formation of these singularities depends on the tilt between two
      Gaussian beams and the separation of their beam axes. By reversing the angle or
      the position of the beams, one can change the sign of the vortex. We have shown
      the formation of single as well as multiple vortices by changing the tilt angle
      and the position of two Gaussian beams. The experimental results are verified
      with theoretical analysis. We also observe that such a vortex structure can be
      formed through superposition of two backreflected Gaussian beams from any optical
      element with two flat surfaces, as illustrated through a beam splitter and a
      neutral density filter. This technique is very useful for generation of vortices
      with high-power lasers where one cannot use a spatial light modulator. 

PMID- 24085163
TI  - Optical component: nonreciprocal three-way divider based on magneto-optical
      resonator.
AB  - We suggest and analyze a new compact nonreciprocal optical component based on a
      magneto-optical (MO) resonator. This component fulfills simultaneously two
      functions, namely, equal division of the input signal between three output ports
      and isolation of the input port from output ones. Using group theory, we analyze
      the scattering matrix of this symmetrical component. Our numerical results for
      one of the possible schemes of the divider based on 2D photonic crystal with MO
      material demonstrate that, at the central frequency, the division of the signal
      between the three output ports is about -6.4 dB. The variation of the division
      levels in the output ports in this band is (-6.4+/-0.4) dB. For two of the output
      ports, the calculated bandwidth for the level -20 dB of the isolation is around
      219 GHz at the wavelength 1.55 MUm. For the third output port, the isolation at
      the central frequency is about -6 dB.

PMID- 24085164
TI  - Fiber polarization control based on a fast locating algorithm.
AB  - In this article, currently used feedback control algorithms used in the
      polarization controller, including a simulated annealing algorithm and a gradient
      algorithm, are analyzed. On this basis, a new method of polarization control
      feedback algorithm based on a fast locating algorithm is proposed to solve the
      defects of the original algorithm, such as poor convergence and an extensive time
      consuming search. It can reduce convergence time and improve the response speed
      of the polarization controllers. This new endless polarization control algorithm
      utilizing a four-plate polarization controller is proposed and demonstrated. The
      results have shown that the response time of the polarization controller is less
      than 1 ms. The control of polarization is achieved and the output polarization
      state is stable, while the light intensity fluctuated less than 2%, which can run
      endless resets freely. 

PMID- 24085165
TI  - Current-voltage characteristics and increase in the quantum efficiency of three
      terminal gate and avalanche-based silicon LEDs.
AB  - In this paper, the emission of visible light by a monolithically integrated
      silicon p-n junction under reverse-bias is discussed. The modulation of light
      intensity is achieved using an insulated-gate terminal on the surface of the p-n
      junction. By varying the gate voltage, the breakdown voltage of the p-n junction
      will be adjustable so that the reverse current I(sub) flowing through the p-n
      junction at a fixed reverse-bias voltage is changed. It is observed that the
      light, which is emitted from the defects located at the p-n junction, depends
      closely on the reverse current I(sub). In regard to the phenomenon of
      electroluminescence, the relationship between the optical emission power and the
      reverse current I(sub) is linear. On the other hand, it is observed that both the
      quantum efficiency and the power conversion efficiency are able to have obvious
      enhancement, although the reverse-bias of the p-n junction is reduced and the
      corresponding reverse-current is much lower. Moreover, the successful fabrication
      on monolithic silicon light source on the bulk silicon by means of standard
      silicon complementary metal-oxide-semiconductor process technology is presented.

PMID- 24085166
TI  - Polarization-insensitive and broad-angle self-collimation in a two-dimensional
      photonic crystal with rectangular air holes.
AB  - In this paper, we have systematically investigated the polarization-insensitive
      and broad-angle self-collimation behavior in a square-lattice two-dimensional
      photonic crystal (PhC) with rectangular air holes. By analyzing the band
      structures and the corresponding equi-frequency contours (EFCs), it is found that
      such PhC can show special dispersion properties when the half-length L and half
      width W of rectangular air holes are appropriately changed. First, compared with
      conventional square-lattice PhCs with circular or square air holes, such PhC is
      easier to support polarization-insensitive self-collimation (PISC) based on the
      EFCs for the second band. Meanwhile, the PISC behavior such as working frequency
      range and effective incident angle can be more flexibly adjusted by changing the
      structural parameters of rectangular air holes. Second, such PhC can show long
      flat EFCs for the TM-3 band. This is quite helpful for supporting broad-angle
      self-collimation. In particular, when L=0.5a and W/L=0.8, this PhC will
      degenerate to a one-dimensional grating PhC. It can show good all-angle self
      collimation behavior with an improved relative bandwidth (about 19.98%) compared
      with previous works. It also presents advantages in practical applications due to
      a relatively convenient fabrication process. 

PMID- 24085167
TI  - Benefits of glass fibers in solar fiber optic lighting systems.
AB  - The transmission properties and coupling of solar light have been studied for
      glass core multimode fibers in order to verify their benefits for a solar fiber
      optic lighting system. The light transportation distance can be extended from 20
      m with plastic fibers to over 100 m with the kind of glass fibers studied here. A
      high luminous flux, full visible spectrum, as well as an outstanding color
      rendering index (98) and correlated color temperature similar to the direct sun
      light outside have been obtained. Thus the outstanding quality of solar light
      transmitted through these fibers would improve the visibility of all kinds of
      objects compared to fluorescent and other artificial lighting. Annual relative
      lighting energy savings of 36% in Uppsala, Sweden, and 76% in Dubai were
      estimated in an office environment. The absolute savings can be doubled by using
      glass optical fibers, and are estimated to be in the order of 550 kWh/year in
      Sweden and 1160 kWh/year in Dubai for one system of only 0.159 m(2) total light
      collecting area. The savings are dependent on the fiber length, the daily usage
      time of the interior, the type of artificial lighting substituted, the system
      light output flux, and the available time of sunny weather at the geographic
      location.

PMID- 24085168
TI  - Measurement of long focal lengths with a double-grating interferometer.
AB  - A method for measuring long focal lengths using a double-grating interferometer
      is proposed. The intensity distribution of a double-grating interferometer
      illuminated by a spherical beam is derived with diffraction theory. A tiny
      rotation angle is set between the two gratings, and a high-contrast interference
      pattern is produced by the adjacent diffracted orders. The angular change in the
      fringes after insertion of a test lens is a measure of the focal length. The
      uncertainty due to aberration of the collimated beam was analyzed by measuring a
      series of lenses. The relative deviations are less than 0.1%. 

PMID- 24085169
TI  - Fabrication and characterization of improved Ag/PS hollow-glass waveguides for
      THz transmission.
AB  - This study involves the fabrication and characterization of improved quality
      silver (Ag)/polystyrene (PS) thin-film-coated hollow-glass waveguides for the low
      loss transmission of terahertz radiation via modified dynamic liquid phase
      deposition techniques. High-quality PS thin films were deposited from aqueous PS
      solutions, and the spectral response of fabricated samples was measured from
      lambda=1-100 MUm. Fabricated samples exhibited highly defined spectral responses
      throughout this entire range indicative of PS films of excellent quality. The
      spectra of experimental samples were compared to the theoretical and bulk PS
      spectra in the near-IR and far-IR regions. The thickness of deposited PS thin
      films was found to depend on total sample length and to vary from approximately
      10-16 MUm for sample lengths ranging from 115 to 140 cm. Such PS film thicknesses
      are adequate for low-loss delivery from approximately 2-4 THz. Furthermore, film
      thickness was found to vary minimally along the waveguide length regardless of
      total sample length.

PMID- 24085170
TI  - Method for estimating mean particle size from high-frequency fluctuations in beam
      attenuation or scattering measurements.
AB  - The ability to estimate mean particle size using simple, low-power optical
      instruments promises to greatly expand coverage of particle size measurements in
      the ocean and advance understanding of myriad processes from sediment transport
      to biological carbon sequestration. Here we present a method for estimating the
      mean diameter of particles in suspension from high-resolution time series of
      simple optical measurements, such as beam attenuation or optical backscattering.
      Validation results from a laboratory clay aggregation experiment show a good fit
      with independent mean particle diameter estimates in the 10-80 MUm diameter
      range, with relative biases of 17%-38% and relative root mean square errors of
      10%-24%. In the 80-200 MUm range, quantitative validation data were not
      available, but our mean diameter estimates correlated strongly with particle
      settling rates. 

PMID- 24085171
TI  - Improved measurement accuracy in optical scatterometry using correction-based
      library search.
AB  - Library search is one of the most commonly used methods for solving the inverse
      problem in optical scatterometry. The final measurement accuracy of the
      conventional library search method highly depends on the grid interval selected
      for each parameter in the signature library, and the time cost of the parameter
      extraction increases dramatically when the grid interval is decreasing. In this
      paper, we propose a correction-based library search method to improve the
      measurement accuracy for a pregenerated signature library. We derive a
      formulation to estimate the error between the expected solution of the inverse
      problem and the actually searched solution obtained by the conventional library
      search method. Then we use the estimate of the error as a correction term to
      correct the actually searched solution to improve the measurement accuracy.
      Experiments performed on a photoresist grating have demonstrated that the
      proposed correction-based library search method can achieve much more accurate
      measurement with negligible computational penalty to the conventional library
      search method in the parameter extraction. It has also been observed that the
      correction-based library search method has higher measurement accuracy and less
      time cost than the interpolation-based library search method. The proposed
      correction-based library search method is expected to provide a more practical
      means to solve the inverse problem in state-of-the-art optical scatterometry. 

PMID- 24085172
TI  - Anamorphic transformation and its application to time-bandwidth compression.
AB  - A general method for compressing the modulation time-bandwidth product of analog
      signals is introduced. As one of its applications, this physics-based signal
      grooming, performed in the analog domain, allows a conventional digitizer to
      sample and digitize the analog signal with variable resolution. The net result is
      that frequency components that were beyond the digitizer bandwidth can now be
      captured and, at the same time, the total digital data size is reduced. This
      compression is lossless and is achieved through a feature selective reshaping of
      the signal's complex field, performed in the analog domain prior to sampling. Our
      method is inspired by operation of Fovea centralis in the human eye and by
      anamorphic transformation in visual arts. The proposed transform can also be
      performed in the digital domain as a data compression algorithm to alleviate the
      storage and transmission bottlenecks associated with "big data." 

PMID- 24085173
TI  - 230 W average-power all-fiber-based actively Q-switched fiber master oscillator
      power amplifier.
AB  - We report a high-power all-fiber format pulsed laser source at ~1064 nm in a
      master oscillator-power amplifier configuration. The seed source is an acousto
      optic Q-switched fiber laser with a varied pulse duration and repetition rate.
      The output power of the oscillator is ~1 W, and two double-cladding Yb-doped
      fiber amplifiers were used to boost the average power of the seed. >230 W average
      power was achieved for ~1.4 MUs pulses at 100 kHz repetition rate. The optical-to
      optical efficiency of the main amplifier is 72.81%.

PMID- 24085174
TI  - Radiant fluxes from various off-axis point sources incident on a circular disk.
AB  - A general multidomain integral formula is presented for calculating fluxes of
      radiation striking a circular disk from various off-axis point source types
      embedded in an attenuating or nonattenuating medium. This formula is expressed by
      double line integrals of radiant intensity and sine functions with respect to the
      polar and horizontal angles determining the angular distribution of the emitted
      radiation. The formula reduces to single line integral expressions when radiation
      does not depend on the horizontal angle and is directly applicable for
      calculating fluxes of revolutional symmetry around the optical axis of the source
      perpendicular to the disk. The applicability of this reduced formula is tested by
      computing radiant fluxes from Lambertian and Gaussian point sources using a
      simple numerical procedure for single integrals. The computed data are
      illustrated graphically, tabulated, and validated using OSLO. Finally, the
      accuracy, similarity, and applicability of the results provided by the integral
      formula and the OSLO program are analyzed. Numerical results have shown the
      effectiveness of the presented formulas for calculating radiant fluxes from
      various on- and off-axis point sources passing through a nonattenuating or
      attenuating homogeneous isotropic media and incident on a circular disk
      perpendicular to optical axes of these sources. Practical applications of these
      formulas include optical sensing and metrology, optical coupling, fiber optic for
      biomedical measurements, and creative lighting design. 

PMID- 24085175
TI  - Identification of pixels with stray light and cloud shadow contaminations in the
      satellite ocean color data processing.
AB  - A new flag/masking scheme has been developed for identifying stray light and
      cloud shadow pixels that significantly impact the quality of satellite-derived
      ocean color products. Various case studies have been carried out to evaluate the
      performance of the new cloud contamination flag/masking scheme on ocean color
      products derived from the Visible Infrared Imaging Radiometer Suite (VIIRS)
      onboard the Suomi National Polar-orbiting Partnership (SNPP). These include
      direct visual assessments, detailed quantitative case studies, objective
      statistic analyses, and global image examinations and comparisons. The National
      Oceanic and Atmospheric Administration (NOAA) Multisensor Level-1 to Level-2
      (NOAA-MSL12) ocean color data processing system has been used in the study. The
      new stray light and cloud shadow identification method has been shown to
      outperform the current stray light flag in both valid data coverage and data
      quality of satellite-derived ocean color products. In addition, some cloud
      related flags from the official VIIRS-SNPP data processing software, i.e., the
      Interface Data Processing System (IDPS), have been assessed. Although the data
      quality with the IDPS flags is comparable to that of the new flag implemented in
      the NOAA-MSL12 ocean color data processing system, the valid data coverage from
      the IDPS is significantly less than that from the NOAA-MSL12 using the new stray
      light and cloud shadow flag method. Thus, the IDPS flag/masking algorithms need
      to be refined and modified to reduce the pixel loss, e.g., the proposed new cloud
      contamination flag/masking can be implemented in IDPS VIIRS ocean color data
      processing. 

PMID- 24085176
TI  - Frequency dependence of slab coupled optical sensor sensitivity.
AB  - This paper presents the frequency-dependent sensitivity of slab-coupled optical
      fiber sensors (SCOSs). This dependence is caused by the frequency characteristics
      of the relative permittivity. We show experimentally the frequency dependence of
      SCOS sensitivity for frequencies in the range of 1 kHz to 1 MHz for SCOS
      fabricated with both potassium titanyl phosphate (KTP) and lithium niobate
      (LiNbO(3)). We conclude that x-cut KTP SCOSs are preferred for measuring fields
      above 300 kHz as they are 1.55* more sensitive than x-cut LiNbO(3) SCOSs to the
      higher frequency fields. However, since KTP SCOSs experience increasing
      permittivity for low frequencies, SCOSs made with LiNbO(3) may be used for low
      frequency sensing applications due to their flat sensitivity response. For a 10
      kHz electric field, an x cut LiNbO(3) SCOS is approximately 3.43* more sensitive
      than an x-cut KTP SCOS.

PMID- 24085177
TI  - Solid-state YVO4/Nd:YVO4/KTP green laser system for the generation of
      subnanosecond pulses with adjustable kilohertz repetition rate.
AB  - A solid-state green laser generating subnanosecond pulses with adjustable
      kilohertz repetition rate is presented. This pulse laser system is composed of a
      Q-switched and mode-locked YVO(4)/Nd:YVO(4)/KTP laser simultaneously modulated by
      an electro-optic (EO) modulator and a central semiconductor saturable absorption
      mirror. Because the repetition rate of the Q-switched envelope in this laser
      depends on the modulation frequency of the EO modulator, so long as the
      pulsewidth of the Q-switched envelope is shorter than the cavity roundtrip
      transmit time, i.e., the time interval of two neighboring mode-locking pulses,
      only one mode-locking pulse exists underneath a Q-switched envelope, resulting in
      the generation of subnanosecond pulses with kilohertz repetition rate. The
      experimental results show that the pulsewidth of subnanosecond pulses decreases
      with increasing pump power and the shortest pulse generated at 1 kHz was 450 ps
      with pulse energy as high as 252 MUJ, corresponding to a peak power of 560 kW. In
      addition, this laser was confirmed to have high stability, and the pulse
      repetition rate could be freely adjusted from 1 to 4 kHz.

PMID- 24085178
TI  - Low-cost vibration sensor based on dual fiber Bragg gratings and light intensity
      measurement.
AB  - A vibration monitoring system based on light intensity measurement has been
      constructed, and the designed accelerometer is based on steel cantilever frame
      and dual fiber Bragg gratings (FBGs). By using numerical simulations for the dual
      FBGs, the dependence relationship of the area of main lobes on the difference of
      initial central wavelengths is obtained and the most optimal choice for the
      initial value and the vibration amplitude of the difference of central
      wavelengths of two FBGs is suggested. The vibration monitoring experiments are
      finished, and the measured data are identical to the simulated results. 

PMID- 24085179
TI  - Color selectivity of surface-plasmon holograms illuminated with white light.
AB  - By using the optical frequency dependence of surface-plasmon polaritons, color
      images can be reconstructed from holograms illuminated with white light. We
      report details on the color selectivity of the color holograms. The selectivity
      is tuned by the thickness of a dielectric film covering a plasmonic metal film.
      When the dielectric is SiO(2) and the metal is silver, the appropriate
      thicknesses are 25 and 55 nm, respectively. In terms of spatial color uniformity,
      holograms made of silver-film corrugations are better than holograms recorded on
      photographic film on a flat silver surface.

PMID- 24085180
TI  - Noise-aware image deconvolution with multidirectional filters.
AB  - In this paper we propose an approach for handling noise in deconvolution
      algorithm based on multidirectional filters. Most image deconvolution techniques
      are sensitive to the noise. Even a small amount of noise will degrade the quality
      of image estimation dramatically. We found that by applying a directional low
      pass filter to the blurred image, we can reduce the noise level while preserving
      the blur information in the orthogonal direction to the filter. So we apply a
      series of directional filters at different orientations to the blurred image, and
      a guided filter based edge-preserving image deconvolution is used to estimate an
      accurate Radon transform of the clear image from each filtered image. Finally, we
      reconstruct the original image using the inverse Radon transform. We compare our
      deconvolution algorithm with many competitive deconvolution techniques in terms
      of the improvement in signal-to-noise ratio and visual quality. 

PMID- 24085181
TI  - Slope efficiency over 30% single-frequency ytterbium-doped fiber laser based on
      Sagnac loop mirror filter.
AB  - A high-slope-efficiency single-frequency (SF) ytterbium-doped fiber laser, based
      on a Sagnac loop mirror filter (LMF), was demonstrated. It combined a simple
      linear cavity with a Sagnac LMF that acted as a narrow-bandwidth filter to select
      the longitudinal modes. And we introduced a polarization controller to restrain
      the spatial hole burning effect in the linear cavity. The system could operate at
      a stable SF oscillating at 1064 nm with the obtained maximum output power of 32
      mW. The slope efficiency was found to be primarily dependent on the reflectivity
      of the fiber Bragg grating. The slope efficiency of multi-longitudinal modes was
      higher than 45%, and the highest slope efficiency of the single longitudinal mode
      we achieved was 33.8%. The power stability and spectrum stability were <2% and
      <0.1%, respectively, and the signal-to-noise ratio measured was around 60 dB. 

PMID- 24085182
TI  - Fringe phase extraction using windowed Fourier transform guided by principal
      component analysis.
AB  - The windowed Fourier transform (WFT) has been recognized as an effective tool for
      extracting phase map from a single fringe pattern. This paper presents a new WFT
      based algorithm, which is guided by the principal component analysis (PCA) of the
      fringe pattern. With it, the principal direction of frequency at each pixel is
      determined first by using the PCA of the gradients of the fringe pattern, and
      then the windowed Fourier ridge for each pixel is detected by searching a one
      dimensional space of frequency, so that the computational burden for phase
      extraction is alleviated significantly. In addition, this technique enables
      automatically identifying and excluding the regions of singular points from the
      fringe pattern by using the eigenvalues resulting from the PCA just mentioned.
      Numerical simulation and experiment are carried out to demonstrate the validity
      of this method. 

PMID- 24085183
TI  - Field trial of active remote sensing using a high-power short-wave infrared
      supercontinuum laser.
AB  - Field trial results of a 5 W all-fiber broadband supercontinuum (SC) laser
      covering the short-wave infrared (SWIR) wavelength bands from ~1.55 to 2.35 MUm
      are presented. The SC laser is kept on a 12 story tower at the Wright Patterson
      Air Force Base and propagated through the atmosphere to a target 1.6 km away.
      Beam quality of the SC laser after propagating through 1.6 km is studied using a
      SWIR camera and show a near diffraction limited beam with an M(2) value of <1.3.
      The SC laser is used as the illumination source to perform spectral reflectance
      measurements of various samples at 1.6 km, and the results are seen to be in good
      agreement with in-lab measurements using a conventional lamp source. Spectral
      stability measurements are performed after atmospheric propagation through 1.6 km
      and show a relative variability of ~4%-8% across the spectrum depending on the
      atmospheric turbulence effects. Spectral stability measurements are also
      performed in-lab and show a relative variability of <0.6% across the spectrum.

PMID- 24085184
TI  - Design and fabrication of a supermirror with smooth and broad response for hard x
      ray telescopes.
AB  - We present our design and fabrication scheme of a supermirror for hard x-ray
      telescopes to improve the performance of reflection. Supermirrors are designed to
      achieve target reflectivity profiles with small ripples in the interesting energy
      range with a limited number of layer pairs. Starting from conventional design
      methods, we optimized the thickness distribution of the structure using a
      numerical approach with the merit function established for this application. As
      an example, a platinum-carbon supermirror structure of 123 layer pairs with a
      varying d-space of 2-6 nm was designed to enhance the reflectivity in the energy
      range from 11 to 55 keV with a flat top at a grazing angle of 0.28 deg. The
      multilayer thus designed was deposited on a float glass by our DC magnetron
      sputtering system. The reflectivity profile was successfully measured to be ~20%
      with little oscillation in all energy band of interest.

PMID- 24085185
TI  - Theoretical and experimental study of a catadioptric compensator for an aspheric
      surface.
AB  - A new type of catadioptric compensator is established. The tolerance values of
      lens spacing, lens thickness, and tilt in mounting are about three times higher
      than that of the Offner compensator. They overcome the localization of the Offner
      compensator, improve the test validity, and reduce the test risk of system
      detection by cross-validation with existing means. The performance of the
      catadioptric compensator is verified in experiments and theoretically. 

PMID- 24085186
TI  - Three-degree-of-freedom displacement measurement using grating-based heterodyne
      interferometry.
AB  - A heterodyne grating-based interferometer for three-degree-of-freedom (3-DOF)
      displacement measurement is proposed. This technique has the merits of both
      heterodyne interferometry and grating interferometry. A heterodyne light beam is
      obtained using an electro-optic modulating technique for amplitude modulation.
      While the heterodyne light beam is normally incident into a transmission-type 2D
      grating, two detection parts for in-plane and out-of-plane displacement
      measurements will be obtained. The heterodyne light beam is utilized to carry the
      optical phase variation that results from grating displacement in three
      directions. The experimental results demonstrate that the proposed interferometer
      is capable of sensing the displacement of a motion stage in 3-DOF. The resolution
      and range of the measurement can achieve up to nanometric and millimetric levels.

PMID- 24085187
TI  - A tensile deformation model for in-situ dendrite/metallic glass matrix
      composites.
AB  - In-situ dendrite/metallic glass matrix composites (MGMCs) with a composition of
      Ti46Zr20V12Cu5Be17 exhibit ultimate tensile strength of 1510 MPa and fracture
      strain of about 7.6%. A tensile deformation model is established, based on the
      five-stage classification: (1) elastic-elastic, (2) elastic-plastic, (3) plastic
      plastic (yield platform), (4) plastic-plastic (work hardening), and (5) plastic
      plastic (softening) stages, analogous to the tensile behavior of common carbon
      steels. The constitutive relations strongly elucidate the tensile deformation
      mechanism. In parallel, the simulation results by a finite-element method (FEM)
      are in good agreement with the experimental findings and theoretical
      calculations. The present study gives a mathematical model to clarify the work
      hardening behavior of dendrites and softening of the amorphous matrix.
      Furthermore, the model can be employed to simulate the tensile behavior of in
      situ dendrite/MGMCs.

PMID- 24085188
TI  - Feature selection of gas chromatography/mass spectrometry chemical profiles of
      basil plants using a bootstrapped fuzzy rule-building expert system.
AB  - A bootstrapped fuzzy rule-building expert system (FuRES) and a bootstrapped t
      statistical weight feature selection method were individually used to select
      informative features from gas chromatography/mass spectrometry (GC/MS) chemical
      profiles of basil plants cultivated by organic and conventional farming
      practices. Feature subsets were selected from two-way GC/MS data objects, total
      ion chromatograms, and total mass spectra, separately. Four economic classifiers
      based on the bootstrapped FuRES approach, i.e., fuzzy optimal associative memory
      (e-FOAM), e-FuRES, partial least-squares-discriminant analysis (e-PLS-DA), and
      soft independent modeling by class analogy (e-SIMCA), and four economic
      classifiers based on the bootstrapped t-weight approach, i.e., e-PLS-DA-t, e-FOAM
      t, e-FuRES-t, and e-SIMCA-t, were constructed thereafter to be compared with full
      size classifiers obtained from the entire GC/MS data objects (i.e., FOAM, FuRES,
      PLS-DA, and SIMCA). By using three features selected from two-way data objects,
      the average classification rates with e-FOAM, e-FuRES, e-PLS-DA, and e-SIMCA were
      95.3 +/- 0.5%, 100%, 100%, and 91.8 +/- 0.2%, respectively. The established
      economic classifiers were used to classify a new validation set collected 2.5
      months later with no parametric change to experimental procedure. Classification
      rates with e-FOAM, e-FuRES, e-PLS-DA, and e-SIMCA were 96.7%, 100%, 100%, and
      96.7%, respectively. Characteristic components in basil extracts corresponding to
      highest-ranked useful features were putatively identified. The feature subset may
      prove valuable as a rapid approach for organic basil authentication.

PMID- 24085189
TI  - Structure elucidation and HPLC-MS/MS determination of a potential biomarker for
      estradiol administration in cattle.
AB  - Administration of hormonal compounds as growth promoters in livestock farming was
      banned by Council Directive 96/22/EC. However, this kind of substances is
      sometimes reported within the framework of European monitoring residue plans.
      Various analytical methods have been previously developed to screen for their
      misuse, and they are now especially efficient for monitoring the illegal
      administration of synthetic and semisynthetic hormones. Nevertheless, proving an
      exogenous administration of hormones from natural origin (i.e., estradiol-17beta
      or progesterone) still remains a challenge for European authorities. These target
      compounds are indeed always present in the animal matrix, and the establishment
      of reference thresholds appears very difficult because of the extreme variability
      existing among animals. In 2011, a metabolomics study was performed on serum
      samples obtained from cows treated with estradiol-17beta (or its ester estradiol
      benzoate) and from control animals using a high-performance liquid chromatography
      (HPLC)-LTQ-Orbitrap system. After appropriate data processing and multivariate
      statistical analysis (orthogonal partial least squares discriminant analysis), it
      was possible to highlight one potential biomarker candidate of estradiol
      treatments in bovine animals. Now, this biomarker has been structurally
      elucidated as a dipeptide, and its usefulness has been tested through a targeted
      HPLC-MS/MS method. Its presence in the previous samples has been confirmed and
      also in additional samples from estradiol-treated animals. 

PMID- 24085190
TI  - Evaluation of serum bile acid profiles as biomarkers of liver injury in rodents.
AB  - Bile acids (BAs) have been studied as potential biomarkers of drug-induced liver
      injury. However, the relationship between levels of individual BAs and specific
      forms of liver injury remains to be fully understood. Thus, we set out to
      evaluate cholic acid (CA), glycocholic acid (GCA), and taurocholic acid (TCA) as
      potential biomarkers of liver injury in rodent toxicity studies. We have
      developed a sensitive liquid chromatography-tandem mass spectrometry (LC/MS/MS)
      assay applicable to rat and mouse serum and evaluated levels of the individual
      BAs in comparison with the classical biomarkers of hepatotoxicity (alanine
      aminotransferase [ALT], aspartate aminotransferase [AST], glutamate dehydrogenase
      (GLDH), alkaline phosphatase, total bilirubin, gamma-glutamyl transferase, and
      total BAs) and histopathology findings in animals treated with model toxicants.
      The pattern of changes in the individual BAs varied with different forms of liver
      injury. Animals with histopathologic signs of hepatocellular necrosis showed
      increases in all 3 BAs tested, as well as increases in ALT, AST, GLDH, and total
      BAs. Animals with histopathologic signs of bile duct hyperplasia (BDH) displayed
      increases in only conjugated BAs (GCA and TCA), a pattern not observed with the
      other toxicants. Because BDH is detectable only via histopathology, our results
      indicate the potential diagnostic value of examining individual BAs levels in
      serum as biomarkers capable of differentiating specific forms of liver injury in
      rodent toxicity studies. 

PMID- 24085191
TI  - Tungsten carbide-cobalt as a nanoparticulate reference positive control in in
      vitro genotoxicity assays.
AB  - With the increasing human exposure to nanoparticles (NP), the evaluation of their
      genotoxic potential is of significant importance. However, relevance for NP of
      the routinely used in vitro genotoxicity assays is often questioned, and a
      nanoparticulate reference positive control would therefore constitute an
      important step to a better testing of NP, ensuring that test systems are really
      appropriate. In this study, we investigated the possibility of using tungsten
      carbide-cobalt (WC-Co) NP as reference positive control in in vitro genotoxicity
      assays, including 2 regulatory assays, the mouse lymphoma assay and the
      micronucleus assay, and in the Comet assay, recommended for the toxicological
      evaluation of nanomedicines by the French Agency of Human Health Products
      (Afssaps). Through these assays, we were able to study different genetic
      endpoints in 2 cell types commonly used in regulatory genotoxicity assays: the
      L5178Y mouse lymphoma cell line and primary cultures of human lymphocytes. Our
      results showed that the use of WC-Co NP as positive control in in vitro
      genotoxicity assays was conceivable, but that different parameters have to be
      considered, such as cell type and treatment schedule. L5178Y mouse lymphoma cells
      did not provide satisfactory results in the 3 performed tests. However, human
      lymphocytes were more sensitive to genotoxic effects induced by WC-Co NP,
      particularly after a 24-h treatment in the in vitro micronucleus assay and after
      a 4-h treatment in the in vitro Comet assay. Under such conditions, WC-Co could
      be used as a nanoparticulate reference positive control in these assays. 

PMID- 24085192
TI  - A correlation between the in vitro drug toxicity of drugs to cell lines that
      express human P450s and their propensity to cause liver injury in humans.
AB  - Drug toxicity to T-antigen-immortalized human liver epithelial (THLE) cells
      stably transfected with plasmid vectors that encoded human cytochrome P450s 1A2,
      2C9, 2C19, 2D6, or 3A4, or an empty plasmid vector (THLE-Null), was investigated.
      An automated screening platform, which included 1% dimethyl sulfoxide (DMSO)
      vehicle, 2.7% bovine serum in the culture medium, and assessed 3-(4,5
      dimethylthiazol-2-yl)-5-(3-carboxymethoxyphenyl)-2-(4-sulfophenyl)-2H-tetrazolium
      reduction, was used to evaluate the cytotoxicity of 103 drugs after 24h. Twenty
      two drugs caused cytotoxicity to THLE-Null cells, with EC50 <= 200 MUM; 21 of
      these drugs (95%) have been reported to cause human liver injury. Eleven drugs
      exhibited lower EC50 values in cells transfected with CYP3A4 (THLE-3A4 cells)
      than in THLE-Null cells; 10 of these drugs (91%) caused human liver injury. An
      additional 8 drugs, all of which caused human liver injury, exhibited potentiated
      THLE-3A4 cell toxicity when evaluated using a manual protocol that included 0.2%
      or 1% DMSO, but not bovine serum. Fourteen of the drugs that exhibited
      potentiated THLE-3A4 cell toxicity are known to be metabolized by P450s to
      reactive intermediates. These drugs included troglitazone, which was shown to
      undergo metabolic bioactivation and covalent binding to proteins in THLE-3A4
      cells. A single drug (rimonabant) exhibited marked THLE cell toxicity but did not
      cause human liver injury; this drug had very low reported plasma exposure. These
      results indicate that evaluation of toxicity to THLE-Null and THLE-3A4 cell lines
      during drug discovery may aid selection of drugs with reduced propensity to cause
      drug-induced liver injury and that consideration of human exposure is required to
      enhance data interpretation.

PMID- 24085193
TI  - E2012-induced cataract and its predictive biomarkers.
AB  - E2012, a gamma secretase modulator without affecting Notch processing, aimed at
      Alzheimer's disease by reduction of amyloid beta-42, induced cataract following
      repeated doses in the rat. Cataract appeared first at week 10-11 of treatment as
      a posterior subcapsular area with granular/punctate opaque or shiny dots along
      the suture line, characterized histologically as lenticular fiber degeneration,
      which eventually coalesced to form a triangular or circular opacity. It was
      associated with prolonged and sustained elevation of lenticular desmosterol (24
      dehydrocholesterol), the final precursor of cholesterol, and decrease in
      lenticular cholesterol. In vitro studies to investigate the effect of E2012 on
      cholesterol metabolism demonstrated that E2012 inhibits 3beta-hydroxysterol
      Delta24-reductase (DHCR24) at the final step in the cholesterol biosynthesis. In
      vivo lenticular concentration of E2012 after 13-week repeated dose with cataract
      was well above those where inhibition was observed in vitro. There was no
      cataract formation at doses where desmosterol did not accumulate in the lens. The
      elevation of desmosterol and decreased cholesterol levels were also seen in the
      liver and plasma and preceded those in the lens. These results demonstrate that
      E2012 induces cataract in the rat by inhibiting DHCR24 at the final step of
      cholesterol synthesis with associated elevation in desmosterol within the lens,
      preceded by desmosterol changes that would serve as a predictive safety biomarker
      for lenticular opacity. 

PMID- 24085194
TI  - Detection and genome analysis of human bocavirus 1-4 from hospitalized children
      with acute lower respiratory tract infection and symptoms of wheezing in
      Shanghai.
AB  - The aim of this study was to elucidate the clinical and molecular epidemiology of
      human bocavirus (HBoV)1-4 in hospitalized children in Shanghai suffering from
      acute lower respiratory tract infection with symptoms of wheezing. HBoV1-4 was
      detected by nested PCR from 275 nasopharyngeal secretion samples collected from
      hospitalized children. The HBoV-positive DNA sequences were aligned and
      phylogenetic trees were constructed. The detection rate of HBoV1 was 5.45%
      (15/275), which was second only to respiratory syncytial virus (RSV). HBoV1 was
      co-detected with other potential pathogens in most of the samples. No sample was
      HBoV2-4-positive. Homology analysis of the partial VP1/VP2, NP1 and NS1 sequences
      revealed that these genes belonged to the same HBoV1 genotype. Furthermore, the
      phylogenetic analysis indicated that these epidemic strains clustered on one
      independent branch. Our results demonstrate that HBoV1 may be one of the common
      pathogens responsible for the hospitalization of children with acute lower
      respiratory tract infection and symptoms of wheezing in Shanghai. HBoV1 infection
      cases are often associated with other pathogens. The viral strains responsible
      for winter epidemics circulating among children in Shanghai belonged to the same
      genotype of HBoV1; thus, they may be derived from one common ancestor. 

PMID- 24085198
TI  - Multiple-image encryption based on interference principle and phase-only mask
      multiplexing in Fresnel transform domain.
AB  - In this article, a multiple-image encryption method based on the optical
      interference principle and phase-only mask (POM) multiplexing is proposed. During
      the encryption process, each secret image is encoded into two analytically
      obtained POMs and one computer-generated random POM, in which no iterative
      computation is required. The analytically obtained POMs taken from different
      secret images are then synthesized by POM multiplexing and further encoded into
      two complex ciphertext images. The silhouette problem that exists in the earlier
      interference principle-based encryption approaches is totally resolved by the
      proposal. Both digital and optical means can be used for decryption. The
      crosstalk effect between the secret images will not appear in the decrypted
      results by using the proposed system. Numerical simulations have been given to
      verify the performance and feasibility of the proposal. We also discuss briefly
      the influence of information compression on the quality of decrypted images. 

PMID- 24085196
TI  - Hyperexpression of HOXC13, located in the 12q13 chromosomal region, in well
      differentiated and dedifferentiated human liposarcomas.
AB  - Liposarcoma (LPS) is the most common soft tissue neoplasm in adults and is
      characterized by neoplastic adipocyte proliferation. Some subtypes of LPSs show
      aberrations involving the chromosome 12. The most frequent are t(12;16) (q13;p11)
      present in more than 90% of myxoid LPSs and 12q13-15 amplification in well
      differentiated and dedifferentiated LPSs. In this region, there are important
      oncogenes such as CHOP (DDIT3), GLI, MDM2, CDK4, SAS, HMGA2, but also the HOXC
      locus, involved in development and tumor progression. In this study, we evaluated
      the expression of HOXC13, included in this chromosomal region, in a series of
      adipocytic tumors. We included 18 well-differentiated, 4 dedifferentiated, 11
      myxoid and 6 pleomorphic LPSs as well as 13 lipomas in a tissue microarray. We
      evaluated the HOXC13 protein and gene expression by immunohistochemistry and
      quantitative PCR. Amplification/translocation of the 12q13-15 region was verified
      by FISH. Immunohistochemical HOXC13 overexpression was observed in all well
      differentiated and dedifferentiated LPSs, all characterized by the chromosome
      12q13-15 amplification, and confirmed by quantitative PCR analysis. In
      conclusion, our data show a deregulation of the HOXC13 marker in well
      differentiated and dedifferentiated LPSs, possibly related to 12q13-15
      chromosomal amplification.

PMID- 24085197
TI  - Acceptability of HPV vaccine for males and preferences for future education
      programs among Appalachian residents.
AB  - Appalachia is a geographic region with several disparities related to human
      papillomavirus (HPV) infection, yet little is known about acceptability of HPV
      vaccine for males among Appalachian residents. HPV vaccine acceptability and
      preferences for future HPV vaccine education programs were examined among
      residents of Appalachian Ohio. Focus groups and in-depth interviews were
      conducted with Appalachian Ohio residents between July and October 2011.
      Participants (n = 102 from 24 focus groups and 5 in-depth interviews) included
      four key stakeholder groups: health care providers, community leaders, parents
      with adolescent sons, and young adult men ages 18 to 26 years. Support for
      vaccinating males against HPV was high among participants, despite low awareness
      and knowledge about HPV vaccine for males. Participants reported three categories
      of potential barriers to vaccinating males against HPV: concerns about vaccine
      safety and side effects, access to care and vaccination logistics, and gender and
      cultural issues. Participants reported that HPV vaccine was viewed as being only
      for females in their communities and that receiving the vaccine may be
      emasculating or embarrassing to males. Participants suggested that future HPV
      vaccine education programs mainly target parents, include basic information about
      HPV-related diseases and HPV vaccine (e.g., number of doses, cost), and present
      the vaccine as having the potential to prevent cancer (as opposed to preventing
      genital warts). Acceptability of HPV vaccine for males was high among residents
      of Appalachian Ohio. Future HPV vaccine education programs in Appalachia should
      address common potential barriers to vaccination and help destigmatize
      vaccination among males. 

PMID- 24085199
TI  - Sampling strategy for the sparse recovery of infrared images.
AB  - The compressive sensing (CS) framework states that a signal that has a sparse
      representation in a known basis may be reconstructed from samples obtained at a
      sub-Nyquist sampling rate. The Fourier domain is widely used in CS applications
      due to its inherent properties. Sparse signal recovery applications using a small
      number of Fourier transform coefficients have made solutions to large-scale data
      recovery problems, including image recovery problems, more practical. The sparse
      reconstruction of 2D images is performed using the sampling patterns generated by
      taking the general frequency characteristics of the images into account. In this
      work, instead of forming a general sampling pattern for infrared (IR) images, a
      special sampling pattern is obtained by gathering a database to extract the
      frequency characteristics of IR sea-surveillance images. Experimental results
      show that the proposed sampling pattern provides better sparse recovery results
      compared to the widely used patterns proposed in the literature. It is also shown
      that, together with a certain image dataset, the sampling pattern generated by
      the proposed scheme can be generalized for various image sparse recovery
      applications. 

PMID- 24085200
TI  - Method for primary design of superachromats.
AB  - This work deals with a method for primary optical design of superachromats, where
      chromatic aberration is corrected for several wavelengths. Equations for the
      calculation of optical power and curvature radii are described for aplanatic and
      nonaplanatic optical systems, which are composed of two or three thin lenses in
      contact. Results of the calculations are presented for chosen optical systems of
      superachromats with basic design parameters. 

PMID- 24085201
TI  - Optimizing the diffraction efficiency of SLM-based holography with respect to the
      fringing field effect.
AB  - The fringing field effect of liquid-crystal displays causes a crosstalk between
      neighboring pixels, so that a desired sharp phase edge gets blurred. This
      blurring effect influences the diffraction efficiency of holograms, which are
      displayed on the spatial light modulator (SLM). In this paper, we show two
      different simulation models for the SLM, one based on the measured subpixel Jones
      matrices of the SLM and the other based on a direction-dependent convolution
      model. Using these models we optimize different blazed gratings written in the
      SLM according to their diffraction efficiency followed by an experimental
      verification. 

PMID- 24085202
TI  - Spectrally resolved Raman lidar measurements of gaseous and liquid water in the
      atmosphere.
AB  - A spectrally resolved Raman lidar based on a tripled Nd:YAG laser is built for
      measuring gaseous and liquid water in the atmosphere. A double-grating
      polychromator with a reciprocal linear dispersion of ~0.237 nm mm(-1) is designed
      to achieve the wavelength separation and the suppression of elastic backscatter.
      A 32-channel linear-array photomultiplier tube is employed to sample atmospheric
      Raman water spectrum between 401.65 and 408.99 nm. The lidar-observed Raman water
      spectrum in the very clear atmosphere is nearly invariable in shape. It is
      dominated by water vapor, and can serve as background reference for Raman lidar
      identification of the phase state of atmospheric water under various weather
      conditions. The lidar has measured also the Raman water spectrum of an
      aerosol/liquid water layer. The spectrum showed a moderate increase of the signal
      on both sides of the Q-branch of water vapor. Noting that under clear weather
      conditions the Raman water spectrum intensity stays at a very low level in the
      401.6-404.7 nm range, the Raman water signal in this portion can be used to
      estimate the liquid water content in the layer.

PMID- 24085203
TI  - Experimental and numerical studies for nondestructive evaluation of human enamel
      using laser ultrasonic technique.
AB  - In this paper, a nondestructive laser ultrasonic technique is used to generate
      and detect broadband surface acoustic waves (SAWs) on human teeth with different
      demineralization treatment. A scanning laser line-source technique is used to
      generate a series of SAW signals for obtaining the dispersion spectrum through a
      two-dimensional fast Fourier translation method. The experimental dispersion
      curves of SAWs are studied for evaluating the elastic properties of the sound
      tooth and carious tooth. The propagation and dispersion of SAWs in human teeth
      are also been studied using the finite element method. Results from numerical
      simulation and experiment are compared and discussed, and the elastic properties
      of teeth with different conditions are evaluated by combining the simulation and
      experimental results. 

PMID- 24085204
TI  - Long-wavelength mid-infrared reflectors using guided-mode resonance.
AB  - We have proposed and fabricated a new mid-infrared reflector using the guided
      mode resonance (GMR). The GMR reflector consists of subwavelength Ge grating on
      GaAs substrate with a low-refractive-index SiOx layer in between. With a total
      thickness of about 2 MUm, a near-100% reflectivity at 8 MUm has been obtained
      both theoretically and experimentally.

PMID- 24085205
TI  - Imaging properties of three refractive axicons.
AB  - The imaging properties of three types of refractive axicons are examined by using
      them in an imaging system. A linear axicon, a logarithmic axicon, and a Fresnel
      axicon are characterized by determining their point spread functions (PSFs)
      experimentally and by numerical simulation. The PSFs, which vary along the depth
      of field for the cases considered in the present investigation, are used in
      digital filters to denoise the images. A comparison of the imaging performance of
      these three optical elements is presented. 

PMID- 24085206
TI  - Wide dynamic range homodyne interferometry method and its application for
      piezoactuator displacement measurements.
AB  - Multiactuated piezoelectric flextensional actuators (MAPFAs) is a fast-growing
      technology in development, with a wide range of applications in precision
      mechanics and nanotechnology. In turn, optical interferometry is an adequate
      technique to measure nano/micro-displacements and to characterize these MAPFAs.
      In this work, an efficient method for homodyne phase detection, based on a well
      known Bessel functions recurrence relation, is developed, providing practical
      applications with a high dynamic range. Fading and electronic noise are taken
      into account in the analysis. An important advantage of the method is that, for
      each measurement, only a limited number of frequencies in the magnitude spectrum
      of the photodetected signal are used, without the need to know the phase
      spectrum. The dynamic range for phase demodulation is from 0.2 to 100pi rad (or
      10 nm to 16 MUm for displacement, using 632.8 nm wavelength). The upper range can
      be easily expanded by adapting the electronic system to the signal
      characteristics. By using this interferometric technique, a new XY nanopositioner
      MAPFA prototype is tested in terms of linearity, displacement frequency response,
      and coupling rate.

PMID- 24085207
TI  - Optical image encoding based on digital holographic recording on polarization
      state of vector wave.
AB  - We propose and analyze a compact optical image encoder based on the principle of
      digital holographic recording on the polarization state of a vector wave. The
      optical architecture is a Mach-Zehnder interferometer with in-line digital
      holographic recording mechanism. The original image is represented by distinct
      polarization states of elliptically polarized light. This state of polarization
      distribution is scrambled and then recorded by a two-step digital polarization
      holography method with random phase distributed reference wave. Introduction of a
      rotation key in the object arm and phase keys in the reference arm can achieve
      the randomization of plaintext. Statistical property of cyphertext is analyzed
      from confusion and diffusion point of view. Fault tolerance and key sensitivity
      of the proposed approach are also investigated. A chosen plaintext attack on the
      proposed algorithm exhibits its high security level. Simulation results that
      support the theoretical analysis are presented. 

PMID- 24085208
TI  - Strategies for efficient and fast wave optics simulation of coded-aperture and
      other x-ray phase-contrast imaging methods.
AB  - We derive a Fourier formulation of coded-aperture x-ray phase-contrast imaging,
      based on the wave theory of optics in the Fresnel approximation. We use this
      model to develop a flexible, efficient, and general simulation algorithm that can
      be easily adapted to other implementations of x-ray phase contrast imaging.
      Likewise, the algorithm enables a simple extension to 2D aperture designs,
      different acquisition schemes, etc. Problems related to numerical implementation
      of the algorithm are analyzed in detail, and simple rules are derived that enable
      us to avoid or at least mitigate them. Finally, comparisons with experimental
      data and data obtained with a different simulation algorithm are presented to
      validate the model and demonstrate its advantages in practical implementations.
      This also enabled us to demonstrate an increase in computational speed of more
      than one order of magnitude over a previous algorithm. 

PMID- 24085209
TI  - Dual-rotor tool path generation and removal error analysis in active feed
      polishing.
AB  - High-quality ultrasmooth surface is needed in modern optics, while the existing
      ultrasmooth surface processing methods are difficult to meet the requirement of
      the surface figure. In order to solve this problem, the active feed polishing
      (AFP) is taken as the research object, and the dual-rotor tool path is put
      forward for this technology. This tool path is generated based on the motion
      synthesis principle, which realizes smooth connection between different sections.
      At the same time, the eccentricity, the speed ratio, the velocity, and other
      parameters can be modified easily, avoiding using the complicated dual-rotor
      polishing mechanism. In order to further analyze the removal error, the removal
      amount calculation method for the dual-rotor path is researched and proposed. The
      simulation analysis results show that the greatest influence factor for the
      removal error is the sampling interval, the influence of the eccentricity and the
      speed ratio is less, and the velocity has little impact on it. In addition, the
      removal error can be controlled within acceptable range by reasonable selection
      of process parameters. Finally, through a processing experiment of a 100 mm plane
      lens, the feasibility and effectiveness of this path is verified. This
      experimental result shows that the AFP technology using the dual-rotor tool path
      can effectively correct the surface shape while reducing the surface roughness.

PMID- 24085210
TI  - Modified Schwarzschild imaging spectrometer with a low F-number and a long slit.
AB  - A modified Schwarzschild imaging spectrometer utilizing three nonconcentric
      aspheric mirrors and a plane grating is designed that can handle low F-number,
      long slit, and broad spectral range. Based on the geometrical aberration theory
      and Rowland circle condition, the astigmatism-correcting method of the
      Schwarzschild imaging spectrometer is analyzed. The design procedure of initial
      parameters is programmed using Matlab software. As an example, a modified
      Schwarzschild imaging spectrometer operating in 400-1000 nm waveband with F
      number of 2.5 and slit length of 13 mm is designed, and good imaging quality is
      obtained.

PMID- 24085211
TI  - Near- to far-field transformation in the aperiodic Fourier modal method.
AB  - This paper addresses the task of obtaining the far-field spectrum for a finite
      structure given the near-field calculated by the aperiodic Fourier modal method
      in contrast-field formulation (AFMM-CFF). The AFMM-CFF efficiently calculates the
      solution to Maxwell's equations for a finite structure by truncating the
      computational domain with perfectly matched layers (PMLs). However, this limits
      the far-field solution to a narrow strip between the PMLs. The Green's function
      for layered media is used to extend the solution over the whole super- and
      substrate. The approach is validated by applying it to the problem of scattering
      from a cylinder for which the analytical solution is available. Moreover, a
      numerical study is conducted on the accuracy of the approximate far-field
      computed with the super-cell Fourier modal method by using the AFMM-CFF with near
      to far-field transformation as a reference. 

PMID- 24085212
TI  - Viewing-zone control of integral imaging display using a directional projection
      and elemental image resizing method.
AB  - Viewing-zone control of integral imaging (II) displays using a directional
      projection and elemental image (EI) resizing method is proposed. Directional
      projection of EIs with the same size of microlens pitch causes an EI mismatch at
      the EI plane. In this method, EIs are generated computationally using a newly
      introduced algorithm: the directional elemental image generation and resizing
      algorithm considering the directional projection geometry of each pixel as well
      as an EI resizing method to prevent the EI mismatch. Generated EIs are projected
      as a collimated projection beam with a predefined directional angle, either
      horizontally or vertically. The proposed II display system allows reconstruction
      of a 3D image within a predefined viewing zone that is determined by the
      directional projection angle. 

PMID- 24085213
TI  - Automated seeding-based nuclei segmentation in nonlinear optical microscopy.
AB  - Nonlinear optical (NLO) microscopy based, e.g., on coherent anti-Stokes Raman
      scattering (CARS) or two-photon-excited fluorescence (TPEF) is a fast label-free
      imaging technique, with a great potential for biomedical applications. However,
      NLO microscopy as a diagnostic tool is still in its infancy; there is a lack of
      robust and durable nuclei segmentation methods capable of accurate image
      processing in cases of variable image contrast, nuclear density, and type of
      investigated tissue. Nonetheless, such algorithms specifically adapted to NLO
      microscopy present one prerequisite for the technology to be routinely used,
      e.g., in pathology or intraoperatively for surgical guidance. In this paper, we
      compare the applicability of different seeding and boundary detection methods to
      NLO microscopic images in order to develop an optimal seeding-based approach
      capable of accurate segmentation of both TPEF and CARS images. Among different
      methods, the Laplacian of Gaussian filter showed the best accuracy for the
      seeding of the image, while a modified seeded watershed segmentation was the most
      accurate in the task of boundary detection. The resulting combination of these
      methods followed by the verification of the detected nuclei performs high average
      sensitivity and specificity when applied to various types of NLO microscopy
      images. 

PMID- 24085214
TI  - Diffraction by metallic planar gratings.
AB  - In this work, a kind of grating that, to our knowledge, has not yet been analyzed
      for diffractive purposes is proposed. The mentioned grating consists of metallic
      intercalated slits of two different metals on a glass substrate. The main
      characteristic and peculiarity of the proposed grating is that it is totally
      planar, without any slopes or grooves. We analyze the intensity distribution at
      the near- and far-field produced by the grating. The method used is rigorous
      coupled wave analysis. We show how the metallic layer thickness is a crucial
      parameter to achieve the highest efficiency of the diffraction orders and,
      therefore, the highest contrast of the diffracted fringes. To conclude, we
      investigate how parameters such as the period, duty cycle, wavelength, or the
      used metals affect the diffracted field. Some nonexpected behaviors have been
      found. As we demonstrate by comparing with other kinds of gratings, the proposed
      grating would be useful in applications in which fringes are needed in both the
      front and back sides of the grating. 

PMID- 24085215
TI  - 1.23 MUm emission of Er/Pr-doped water-free fluorotellurite glasses.
AB  - To investigate the relatively unexplored 1.2 MUm region, we identified a near
      infrared emission at around 1.23 MUm from Er3+/Pr3+-codoped water-free
      fluorotellurite glass with a composition of 60TeO2-30ZnF2-10NaF (TZNF60, mol. %).
      Under the condition of pumping with the 488 nm optical parametric oscillator
      (OPO) laser system, the directly measured lifetime (tau(f)) at 1.23 MUm in Er/Pr
      codoped fluorotellurite glasses is about 111.2 MUs, much longer than that of Er
      doped fluorotellurite glass (80.1 MUs). The stimulated emission cross section
      (sigma(em)) and quantum efficiency (eta) for Er3+:4S3/2->4I11/2 transition are
      greatly enhanced when appropriate Pr3+ ions are incorporated. These advances
      arise partially from the absence of the hydroxyl (OH) group and low phonon energy
      with the addition of a large amount of fluorides into oxide-based host glasses.
      With high quantum efficiency (56.2%) and a large stimulated cross section
      (4.03*10(-21) cm2), Er3+/Pr3+-codoped TZNF60 glass is regarded as promising
      material for the development of optical amplification and laser operation at the
      relatively unexplored 1.2 MUm region.

PMID- 24085216
TI  - HyDRa: polishing process convergence rate optimization.
AB  - In an effort to optimize the hydrodynamic radial (HyDRa) polishing process for
      applications where the amount of material that has to be removed implies long
      polishing times, we have developed a method to determine the optimum correction
      fraction that has to be made for a given error map, in terms of the level of
      determinism of the process, the number of iterations, and their associated
      polishing runs as well as run times. 

PMID- 24085217
TI  - Theoretical investigation of the capture effect in intensity-modulation direct
      detection microwave photonic links.
AB  - We introduce the capture effect concept in microwave photonic links (MWPLs) for
      the first time to our knowledge. The capture effect or the small-signal
      suppression is the change in the amplitude ratio of the two signals between input
      and output of the intensity-modulation direct-detection (IMDD) MWPLs. An
      analytical explanation of the performance of external IMDD MWPLs due to the
      effects of nonlinearity combined with sum of several input sinusoidal signals is
      given. We have investigated the suppression of a weaker signal in these links.
      General analytic expression for the small-signal suppression is derived using a
      nonlinear analytical approach. We show that the small-signal suppression is quite
      dependent on the input back-off, the power ratio of input signals, and on the
      number of input sinusoidal signals. The theoretical maximum possible signal
      suppression was found to be 6 dB. This analytical asymptotic value is verified by
      numerical results. We show the influence of the capture effect of the nonlinear
      MWPL on the optoelectronic oscillator operation that is verified by experimental
      data in the literature that has already been published.

PMID- 24085218
TI  - Designing single LED illumination distribution for direct-type backlight.
AB  - This study presents a new method for achieving uniform illumination of an LED
      array by designing single LED illumination distribution (SLID) on the target
      plane. The SLID with the least coefficient of variation of the root mean squared
      error is calculated. For square LED arrays, the uniformity of illumination
      reaches 0.94. A secondary lens was designed to achieve the calculated SLID.
      Simulation results show that the uniformity of illumination reaches 0.92 when the
      distance-height ratio is 3.33. The calculated SLID can be used in different
      distance-height ratios. When the distance-height ratio is 5, the uniformity of
      illumination reaches 0.91. The calculation method can be used in different kinds
      of LED arrays. A feedback method of lens design is presented for a real direct
      type backlight system. 

PMID- 24085219
TI  - Optimized absolute testing method of shift-rotation.
AB  - The absolute testing method of shift-rotation that combines the traditional N
      position method and Zernike polynomial fitting has been commonly employed in
      surface metrology. It preserves the high spatial frequency of the surface
      deviation with the N-position method to obtain the rotationally asymmetric
      surface deviation, but it suffers the kNtheta order angular terms errors missed
      by the N-position method when it calculates the rotationally symmetric surface
      deviation with the Zernike rotationally symmetric polynomial fitting method. An
      optimized absolute testing method of shift-rotation is presented in this paper.
      It considers the missing kNtheta order errors when the equations of the
      rotationally symmetric surface deviation are solved. As a result, it is more
      accurate than the traditional method. Experimental absolute results of spherical
      surfaces are given. 

PMID- 24085220
TI  - Compressive sensing method for recognizing cat-eye effect targets.
AB  - This paper proposes a cat-eye effect target recognition method with compressive
      sensing (CS) and presents a recognition method (sample processing before
      reconstruction based on compressed sensing, or SPCS) for image processing. In
      this method, the linear projections of original image sequences are applied to
      remove dynamic background distractions and extract cat-eye effect targets.
      Furthermore, the corresponding imaging mechanism for acquiring active and passive
      image sequences is put forward. This method uses fewer images to recognize cat
      eye effect targets, reduces data storage, and translates the traditional target
      identification, based on original image processing, into measurement vectors
      processing. The experimental results show that the SPCS method is feasible and
      superior to the shape-frequency dual criteria method. 

PMID- 24085221
TI  - Polarization holography for vortex retarders recording.
AB  - We present an original static recording method for vortex retarders (VRs) made
      from liquid crystal polymers (LCPs) using the superimposition of several
      polarized beams. VRs are birefringent plates characterized by a rotation of their
      fast axis about their center. The new method is based on polarization holography
      and photo-orientable LCP. Combining several polarized beams induces the
      polarization patterns required for the recording process of VRs without
      mechanical action. A mathematical description of the method, the outcomes of the
      numerical simulations, and the first experimental results are presented. 

PMID- 24085222
TI  - Simple approach for fast real-time line scan microscopic imaging.
AB  - A simple fast line scan microscopic imaging approach based on a wavelength-space
      time mapping technique has been proposed. With a lab-made subpicosecond pulse
      laser with 10 dB bandwidth of 12 nm, we experimentally demonstrate a free-space
      optical apparatus designed for fast line scan imaging of microscopic objects.
      This system has a spatial resolution of 22 MUm, field-of-view of 2.5 mm, and line
      scan rate of 20.9 MHz. By imaging a modified unitraveling carrier photodetector,
      we demonstrate the application of semiconductor device inspection for speeding up
      quality control.

PMID- 24085223
TI  - Prognostic implications of radioiodine avidity and serum thyroglobulin in
      differentiated thyroid carcinoma with distant metastasis.
AB  - BACKGROUND: Although differentiated thyroid carcinoma (DTC) rarely develops
      distant metastases, the present study was performed to evaluate factors that
      affect the survival of patients with DTC who present with distant metastasis.
      METHODS: Among 4,989 patients who underwent thyroid surgery for DTC, 82
      presenting with distant metastasis were analyzed. Based on radioiodine ((131)I)
      avidity and the thyroid-stimulating hormone-stimulated serum thyroglobulin (sTg)
      level at the time of metastasis, patients were divided into three groups: group 1
      ((131)I uptake + sTg <= 215 ng/mL, n = 46), group 2 ((131)I uptake + sTg > 215
      ng/mL, n = 24), group 3 (no (131)I uptake, n = 12). Disease-specific survival
      (DSS) was estimated using the Kaplan-Meier method. Factors predicting the outcome
      were evaluated using Cox proportional hazard regression analysis. RESULTS: The
      age of patients (p = 0.04), frequency of follicular thyroid carcinoma (p =
      0.002), tumor size (p < 0.001), and number of multiple metastatic sites (p =
      0.004) differed significantly among the groups. With a median follow-up after
      surgery of 72 months, the 5- and 10-year DSSs for all patients were 84 and 69 %,
      respectively. The predictors of survival were age (p = 0.004), symptoms at the
      time of presentation (p = 0.045), histology (p = 0.01), sites of metastasis (p =
      0.03), and (131)I avidity and sTg level at the time of metastasis (p = 0.002). In
      the multivariate analysis, age, histology, and (131)I avidity and sTg level at
      the time of metastasis remained significant factors for survival. CONCLUSIONS:
      Certain DTC patients with distant metastasis demonstrate favorable outcomes
      dependent on age, histology, and (131)I avidity and sTg level at the time of
      metastasis.

PMID- 24085225
TI  - ox-LDL downregulates eNOS activity via LOX-1-mediated endoplasmic reticulum
      stress.
AB  - Vascular endothelial injury induced by oxidized low-density lipoprotein (ox-LDL)
      has been implicated in the early stages of the pathogenesis of atherosclerosis.
      In this study, we incubated bovine aortic endothelial cells (BAECs) with ox-LDL
      (100 ug/ml) in order to induce endoplasmic reticulum (ER) stress and to
      investigate the regulation of endothelial nitric oxide synthase (eNOS). Within 4
      h of exposure, ox-LDL rapidly induced ER stress, as demonstrated by the
      measurements of proline-rich extensin-like receptor kinase (PERK) and glucose
      regulated protein (GRP)78. ox-LDL induced the rapid dephosphorylation of eNOS at
      Ser1179 and a subsequent decrease in eNOS activity. This effect appeared to be
      highly specific as no change was observed in the levels of phosphorylated eNOS at
      Thr497 or eNOS protein. Of note, a simultaneous decrease was also observed in the
      active (phosphorylated) form of Akt (Thr308/Ser473), which has been demonstrated
      to phosphorylate eNOS at Ser1179. Further analysis indicated that Brefeldin A
      (BFA), an ER stress-inducing reagent, induced the rapid dephosphorylation of Akt
      and eNOS at Ser1179. 4-Phenylbutyric acid (PBA), an inhibitor of ER stress,
      blocked the ox-LDL-induced dephosphorylation of Akt and eNOS. Furthermore, JTX20,
      a lectin-like ox-LDL receptor-1 (LOX-1) blocking antibody significantly
      eliminated the ability of ox-LDL to mediate the dephosphorylation of eNOS and
      Akt. Our results indicate that the downregulation of eNOS by ox-LDL, as driven by
      LOX-1-mediated ER stress, is associated with the PI3K-Akt-eNOS signaling pathway.

PMID- 24085226
TI  - Significance of INHBA expression in human colorectal cancer.
AB  - Inhibin beta A (INHBA) is a member of the transforming growth factor beta (TGF
      beta) superfamily. INHBA expression is associated with several types of human
      cancers; however, its significance in colorectal cancer (CRC) is not fully
      understood. INHBA expression was studied in 126 primary CRC samples and 4 CRC
      cell lines. Cell growth was assessed after inhibition of INHBA expression or
      after exogenous overexpression of INHBA in CRC tissues. INHBA expression was
      significantly higher in CRC tissues when compared to that in the corresponding
      normal tissues (P<0.001). Patients in the high expression group showed a poorer
      overall survival rate when compared to those in the low expression group
      (P<0.001); the present study did not evaluate for an independent prognostic
      factor but showed the significance of lymph node metastasis as an independent
      prognostic factor. The present study suggests that INHBA is useful as a
      predictive marker for prognosis in CRC patients.

PMID- 24085227
TI  - Impact of age on the efficacy and safety of extended-duration thromboprophylaxis
      in medical patients. Subgroup analysis from the EXCLAIM randomised trial.
AB  - The EXCLAIM study enrolled hospitalised acutely ill medical patients with age >40
      years and recently-reduced mobility into a trial of extended-duration
      anticoagulant thromboprophylaxis. This post-hocanalysis evaluated the impact of
      age on patient outcomes. After completion of open-label therapy with enoxaparin
      40 mg once-daily (10 +/- 4 days), eligible patients underwent randomisation to
      receive double-blind therapy of enoxaparin (n=2,975) or placebo (n=2,988) for 28
      +/- 4 days. During follow-up, the venous thromboembolism (VTE) risk increased
      with age in both treatment groups. In patients with age >75 years, those who
      received extended-duration enoxaparin had lower incidence of VTE (2.5% vs 6.7%;
      absolute difference [AD] [95% confidence interval]: -4.2% [-6.5, -2.0]), proximal
      deep-vein thrombosis (2.5% vs 6.6%; AD -4.1% [-6.2, -2.0]), and symptomatic VTE
      (0.3% vs 1.5%; AD -1.2% [-2.2, -0.3]), in comparison to those who received
      placebo. In patients with age <=75 years, those who received enoxaparin had
      reduced VTE (2.4% vs 2.8%; AD -0.4% [-1.5, 0.7]) and symptomatic VTE (0.2% vs
      0.7%; AD -0.6% [-1.0, -0.1]) in comparison to those who received placebo. In both
      age subgroups, patients who received enoxaparin had increased rates of major
      bleeding versus those who received placebo: age >75 years (0.6% vs 0.2%; AD +0.3%
      [-0.2, 0.9], respectively); age <=75 years (0.7% vs 0.2%; AD +0.5% [0.1, 0.9]).
      Patients in both age subgroups that received enoxaparin had similar low bleeding
      rates (0.6% and 0.7%, respectively). VTE risk increased with age, though the
      bleeding risk did not. Patients with age >75 years had a more favourable benefit
      to-harm profile than younger patients. 

PMID- 24085228
TI  - Soccer goes BOXing: synthetic access to novel [6:0]
      hexakis[(bisoxazolinyl)methano]fullerenes.
AB  - The syntheses of [6:0] hexakis[(bisoxazolinyl)methano]fullerenes are presented.
      Two derivatives could be directly obtained using conditions developed by the Sun
      group. For the remaining products, a two stage protocol had to be developed. All
      compounds we obtained in synthetically useful scales and were purified via column
      chromatography with standard achiral phase. These new fullerene adducts bear six
      metal-chelation sites which are aligned in the three orthogonal space directions
      and are disposed on a completely rigid scaffold. First experiments indicate that
      the generation of six-fold metal-complexes is possible with these structures.
      This makes them very appealing as ligands in asymmetric catalysis and as building
      blocks in higher supra-molecular assemblies. 

PMID- 24085229
TI  - Sight Word and Phonics Training in Children With Dyslexia.
AB  - The aims of this study were to (a) compare sight word training and phonics
      training in children with dyslexia, and (b) determine if different orders of
      sight word and phonics training have different effects on the reading skills of
      children with dyslexia. One group of children (n = 36) did 8 weeks of phonics
      training (reading via grapheme-phoneme correspondence rules) and then 8 weeks of
      sight word training (reading irregular words as a whole), one group did the
      reverse (n = 36), and one group did phonics and sight word training
      simultaneously for two 8-week periods (n = 32). We measured the effects of
      phonics and sight word training on sight word reading (trained irregular word
      reading accuracy, untrained irregular word reading accuracy), phonics reading
      (nonword reading accuracy, nonword reading fluency), and general reading (word
      reading fluency, reading comprehension). Sight word training led to significant
      gains in sight word reading measures that were larger than gains made from
      phonics training, phonics training led to statistically significant gains in a
      phonics reading measure that were larger than gains made from sight word
      training, and both types of training led to significant gains in general reading
      that were similar in size. Training phonics before sight words had a slight
      advantage over the reverse order. We discuss the clinical implications of these
      findings for improving the treatment and assessment of children with dyslexia. 

PMID- 24085230
TI  - Comparison of tamsulosin vs tamsulosin/sildenafil effectiveness in the treatment
      of erectile dysfunction in patients affected by type III chronic prostatitis.
AB  - AIM: We evaluated the effectiveness of tamsulosin monotherapy versus tamsulosin
      plus sildenafil combination therapy on erectile dysfunction (ED) in young
      patients with type III chronic prostatitis and ED by using symptom score scales.
      MATERIALS AND METHODS: 44 male patients were divided into 2 groups: the first
      group (20 patients) was treated with tamsulosin 0,4 mg monotherapy and the second
      one 24 patients) was treated with tamsulosin 0,4 mg plus sildenafil 50 mg
      combination therapy. "International Prostate Symptom Score, "National Institute
      of Health Chronic Prostatitis Symptom Index" (NIH-CPSI) and "International Index
      of Erectile Function" (IIEF-5) were investigated in each group of patients, and
      scores calculated during the first medical examination. Both groups were treated
      with tamsulosin once daily for 60 days, while sildenafil 50 mg was given on
      demand (at least 2 times per week) for 60 days. During the second medical
      examination IPSS, NIH-CPSI and IIEF-5 scores were analyzed once more. Afterwards,
      the alterations of scores among medical examinations in each group and between
      both groups were statistically compared. RESULTS: The age average of the 44 cases
      included was 32.04 3.15 years. Both groups present a statistically significant
      decrease, between the first and the second medical examination, in IPSS, NIH-CPSI
      scores and statistically significant increase in IIEF-5 score. In addition, there
      is no statistically significant difference, in all scores, between mono and
      combination therapy. CONCLUSIONS: tamsulosin monotherapy, as well as a
      combination therapy (tamsulosin plus sildenafil) has an improving effect on
      symptoms and on ED in patients with type III prostatitis. In the near future
      alpha-blockers monotherapy could be used in the treatment of chronic prostatitis
      and ED cases instead of phosphodiesterase type 5 (PDE-5) inhibitors combination
      therapy.

PMID- 24085231
TI  - Caloric restriction increases internal iliac artery and penil nitric oxide
      synthase expression in rat: comparison of aged and adult rats.
AB  - Because of the positive corelation between healthy cardiovascular system and
      sexual life we aimed to evaluate the effect of caloric restriction (CR) on
      endothelial and neuronal nitric oxide synthase (eNOS, nNOS) expression in
      cavernousal tissues and eNOS expression in the internal iliac artery in young and
      aged rats. Young (3 mo, n = 7) and aged (24 mo, n = 7) male Sprague-Dawley rats
      were subjected to 40% CR and were allowed free access to water for 3 months.
      Control rats (n = 14) fed ad libitum had free access to food and water at all
      times. On day 90, rats were sacrificed and internal iliac arteries and penis were
      removed and parafinized, eNOS and nNOS expression evaluated with
      immunohistochemistry. Results were evaluated semiquantitatively. eNOS and nNOS
      expression in cavernousal tis- sue in CR rats were more strong than in control
      group in both young and old rats. eNOS expression was also higher in the internal
      iliac arteries of CR rats than in control in young and old rats. As a result of
      our study we can say that there is a positive link between CR and
      neurotransmitter of erection in cavernousal tissues and internal iliac arteries.
      CR has beneficial effect to prevent sexual dysfunction in young and old animals
      and possible humans.

PMID- 24085232
TI  - Isolated low follicle stimulating hormone (FSH) in infertile males - a
      preliminary report.
AB  - OBJECTIVES: High levels of follicle stimulating hormone (FSH) in infertile males
      received a significant attention and exploration. Studies investigating the
      isolated deficiency of FSH in males are few, and its real prevalence is still
      unknown. Therefore, the objectives of the current study was to report the
      prevalence of isolated low FSH in infertile males and highlight their
      demographics and standard sperm parameters. METHODS: Records of 3335 infertile
      men were retrospectively checked. Patients with isolated low FSH were retrieved.
      FSH levels were categorized into 3 groups based on the number of affected sperm
      parameter (s). Study variables were also arranged into 2 groups in relation to
      smoking history. A control group was included to document the changes in sperm
      morphology. RESULTS: Isolated low FSH (1.146 +/- 0.219 mIU/mL) was found in 29
      (0.87%) patients. All patients showed at least one abnormal sperm parameter. The
      abnormal parameters were present in different combinations within the same
      patient but with no significant correlations with the FSH levels. The FSH levels
      got lower as the number of the affected sperm parameters increased although the
      decline was insignificant. The most frequent abnormal parameter presented was
      sperm morphology (86.2%). Anomalous sperm morphology was highly and significantly
      demonstrated in the head; specifically in acrosome. Abnormal sperm parameters
      were present in both smoking and nonsmoking groups but with no significant
      differences in between. CONCLUSIONS: Isolated low FSH among infertile males has a
      low prevalence. This may be associated with abnormality in semen parameters;
      particularly sperm morphology. These patients are suggested to be found as a
      primary entity. However, an additional work-up is highly recommended to validate
      this hypothesis.

PMID- 24085233
TI  - Comparison between WHO (World Health Organization) 2010 and WHO 1999 parameters
      for semen analysis - interpretation of 529 consecutive samples.
AB  - OBJECTIVE: To quantify how many men with normal semen according to WHO (WHO -
      World Health Organization) 1999 criteria, should be considered with abnormal
      semen according to 2010 criteria and vice versa; to study which parameter of
      volume, concentration, motility and morphology is the most responsible of this
      change. MATERIALS AND METHODS: We studied, using WHO 1999 parameters, 529
      consecutive semen samples from 427 men, collected in our Department from January
      2008 to December 2009, then we re-evaluated those results using WHO 2010
      parameters; we also studied each parameter to understand how changed the
      classification from normal (defined normal by all parameters) to abnormal
      (defined abnormal by at least one parameter) using the two WHO criteria. RESULTS:
      3 men (0.56%) were azoospermic. Among the remaining 526 samples, 199 (37.83%)
      were considered normal and 246 (46.76%) abnormal both according to WHO 1999 and
      WHO 2010 criteria; we found that none of the samples classified normal according
      to the previous criteria was classified abnormal according the more recent
      criteria, while 82 (15.58%) evaluated as abnormal according 1999 criteria changed
      to normal according 2010 criteria. The concordance between 1999 and 2010
      evaluation was 84.44%. CONCLUSIONS: In this study we noted that the changes from
      WHO 1999 to WHO 2010 criteria did not modify the interpretation of semen quality,
      because comparing the two classifications we demonstrated that there is a
      substantial agreement, considering the three parameters (count, motility and
      morphology) all together, and also considering each single parameter. Anyhow,
      almost 16% of the patients considered infertile according to the old criteria,
      should be evaluated normal by the new classification and they should not need any
      treatment for infertility.

PMID- 24085234
TI  - Erectile function after repeat saturation prostate biopsy: our experience in 100
      patients.
AB  - INTRODUCTION: Erectile dysfunction (ED) incidence following repeat saturation
      prostate biopsy (SPBx) was evaluated. MATERIALS AND METHODS: From January 2011 to
      June 2012 295 patients underwent repeat transperineal SPBx (median 28 cores)
      under sedation. The indications for biopsy were: abnormal DRE, PSA > 10 ng/mL or
      included between 4.1-10 with free/total PSA < 25%. All patients were
      prospectively evaluated with the 5-item version of the International Index of
      Erectile Function (IIEF-5) at baseline and 1, 3 and 6 months from SPBx. RESULTS:
      100/200 men with benign histology and normal sexual activity completed the study;
      median IIEF-5 score before and after SPBx was equal to 18.3 (baseline) vs 17.8 (1
      month later) vs 18 (3 months later) vs 18.1 (6 months later) (p > 0.05); in
      detail, 1 month from biopsy 5 (5%) men referred a mild ED that disappeared at 3
      and 6 months evaluation. CONCLUSIONS: Repeat transperineal SPBx under sedation
      did not significantly worsened erectile function; the minimal risk of temporary
      post-biopsy ED could be previously discussed (not emphasised) with potent
      patients.

PMID- 24085235
TI  - Long term patient satisfaction and quality of life with AMS700CX inflatable
      penile prosthesis.
AB  - OBJECTIVE: Penile prosthesis implantation is the solution of choice in patients
      who have failed or present contraindication to the use of all conservative
      treatment for erectile dysfunction (ED). Overall, satisfaction rates are high,
      with more than 80% of patients and partners fully satisfied with cosmetic and
      functional result of surgery. Chronic postoperative pain, penile shortening, soft
      or hyposensitive glans, pencil like penis syndrome and difficulty to cycle the
      device represent the most common causes of patient's dissatisfaction.
      Satisfaction rates are better assessed with the use of validated questionnaires
      such as the International Index of Erectile Function (IIEF) and the Erectile
      Dysfunction Inventory of Treatment Satisfaction (EDITS) The aim of our study was
      to analyze the long-term mechanical reliability of the AMS 700CX/CXM inflatable
      penile prosthesis and the patient's satisfaction rate using IIEF and EDITS
      questionnaire as standard reference. MATERIALS AND METHODS: A retrospective case
      notes review of all patients who have undergone implantation of a three pieces
      inflatable penile prosthesis AMS 700 CX and CXR between October 1997 and December
      2010. Overall, 80 patients have undergone implantation of 3 pieces inflatable
      penile prosthesis AMS 700 CX InhibiZone. Patients have been administered the IIEF
      5 and EDITS questionnaires in combination with a non validated 9 domain
      questionnaire that assesses penile rigidity, sensation, orgasmic function,
      frequency of intercourse, impact of surgery on the quality of life, satisfaction
      rate. RESULTS: Overall 10 years survival estimate according to the Kaplan Meier
      method of AMS 700 CX touch pump and AMS 700 CX momentary squeeze pump are
      respectively 77.6% and 82.5%. The median postoperative IIEF5 and EDITS score were
      respectively 21.46 and 73.11, which show a high level of satisfaction. 59
      patients (90.8%) were able to cycle the device and were engaging in penetrative
      sexual intercourse. CONCLUSIONS: Penile prosthesis implantation yields excellent
      results in terms of cosmetic and functional outcome and therefore has a
      significant impact on patients' satisfaction, sex life and overall quality of
      life. Overall, long term reliability has been significantly improved and
      complication rates are low in the hands of experienced surgeons.

PMID- 24085236
TI  - Axial penile rigidity influences patient and partner satisfaction after penile
      prosthesis implantation.
AB  - INTRODUCTION: Penile prosthesis implantation is one of the treatment choices that
      is kept for patients who were not satisfied with other treatments. Although
      penile prosthesis satisfaction rates are higher, there are some dissatisfied
      patients. The patients' reasons are mostly shortness and softness of implanted
      prosthesis. It was previously demonstrated that penile axial rigidity of more
      than 500 grams is enough for successful vaginal intromission. To our knowledge,
      there is no study comparing axial rigidity of penile prosthesis and satisfaction.
      OBJECTIVES: The aim of this study was to examine whether axial rigidity of penile
      prosthesis had impact on patient and partner satisfaction. MATERIALS AND METHODS:
      We enrolled one hundred patients who were implanted penile prosthesis before to
      evaluate their penile axial rigidity. We used Rigidometry (by using the digital
      inflection rigidometer) to assess the minimal axial pressure to bend the
      implanted penis. RESULTS: We demonstrated that mean axial pressure to bend the
      implanted penis was 984.8 +/- 268.7 grams. Overall satisfaction score with the
      penile prosthesis implant was 4.55 and 4.49 (out of 5) in patients and partners,
      respectively. In total, seven men were unsatisfied with their implant and
      reported a mean satisfaction score of 0.6 +/- 0.48 (out of 5). All prostheses
      types showed good and more than 500 grams axial rigidity. The patients with
      Ambicor type, which were buckled at about 710.5 grams, showed worse satisfaction
      rates in comparison to other prostheses in two patients. Digital inflection
      rigidometer results of other penile prosthesis types in unsatisfied patient were
      842.0, 872.0, 887.0 and 920 g. in CX700, Titan, Genesis and Titan OTR,
      respectively. CONCLUSION: We demonstrated that dissatisfaction rate was highest
      in Ambicor prosthesis implanted patients. Additionally, patients with 3-piece
      penile prosthesis were more satisfied than 2-piece or malleable ones,
      interestingly, although some cases had lower axial rigidity results.

PMID- 24085237
TI  - Varicocele treatment: a 2-centers comparison between non microsurgical open
      correction, laparoscopic approach and retrograde percutaneous sclerotization on
      463 cases.
AB  - OBJECTIVES: To determine whether there are differences in sperm parameters
      improvement after different varicocele correction techniques. To determine the
      role of age in sperm parameters improvement. METHODS: 2 different European
      centers collected pre- and postoperative sperm parameters of patients undergoing
      varicocele correction. Among 463 evaluated patients, 367 were included. Patients
      were divided in procedure-related and age-related groups. Ivanissevich inguinal
      open surgical procedure (OS), lymphatic-sparing laparoscopic approach (LSL) and
      retrograde percutaneous transfemoral sclerotization (RPS) were performed. As
      outcome measurements sperm count (millions/mL, SC) and percentage of mobile
      sperms were analyzed. Univariate and multivariate regression between the defined
      groups; bivariate regression analysis between age and sperm count and motility.
      RESULTS: Number of patients: OS 78; LSL 85; RPS 204. Mean age 30.2 (SD 6.83);
      postoperative SC increased from 18.2 to 30.1 (CI 95% 27.3-32.9; p < 0,001);
      motility from 25.6 to 32.56% (30.9-34.2; p < 0.001). OS: SC varied from 16.9 to
      18.2 (p < 0.001); sperm motility from 29% to 33% (p < 0.001). LSL: SC from 15.5
      to 17.2 (p < 0.001); motility from 27 to 31% (p < 0.001). RPS: SC from 18.9 to
      36.2 (p < 0.001); motility from 24% to 32% (p < 0.001). Univariate and
      multivariate analysis confirmed the significant difference of SC variation in
      RPS, compared to the other groups (p < 0.001). No significance between LSL and OS
      (p = 0.826). No significant differences regarding motility (p = 0.8).
      CONCLUSIONS: Varicocele correction is confirmed useful in improving sperm
      parameters; sclerotization technique leads to a better sperm improvement compared
      to other studied procedures; improvement in seminal parameters is not affected by
      age of the patients treated.

PMID- 24085238
TI  - Results of the surgical correction of urinary stress incontinence according to
      the type of transobturator tape utilized.
AB  - OBJECTIVES: To analyze the short and long term results of tapes of different
      materials used to treat stress urinary incontinence (SUI). A secondary objective
      was to evaluate the ability to adjust the tape after implantation. MATERIALS AND
      METHODS: Retrospective chart review of 355 patients with SUI operated between
      March 2003 and October 2011. Eight different types of transobturator tapes were
      used: Gynecare TVT-O(r), Monarc(r), SAFYRE(r), Contasure KIM(r), I-Stop(r),
      DynaMesh(r), Aris(r) Bandellete and Swing-band(r). Results and complications were
      recorded. RESULTS: The mean age at operation was 61 years. Correction of SUI was
      achieved in 87.88% of cases. The best results were obtained with Contasure KIM(r)
      (98.26 % continence). The tape was well tolerated and was elastic enough to be
      able to be adjusted 48-72 hours after implantation without deformation. Slings
      with macropores and over lock stitches on the superior and inferior borders
      presented the lower rates of postoperative urinary retention, pain, perior
      postoperative bleeding and urinary tract infections. CONCLUSIONS: Transobturator
      tension free tapes require a short operation time and have a low complication
      rate. The possibility of adjustment in the early postoperative period increases
      the success rate and reduces complications. Knotless meshes with macropores and
      over lock stitches appear to be better balanced, are quite resistant to
      stretching and deformation when readjusted after implantation and present a low
      infection rate.

PMID- 24085239
TI  - Prostatic abscess: case report and review of the literature.
AB  - We report a case of prostatic abscess in a 52 year old male with a history of
      diabetes mellitus. The abscess was treated successfully with surgical drainage by
      transurethral unroofing of the cavity of the abscess. The use of transrectal
      ultrasound is valuable in the diagnosis, treatment and follow up of the abscess,
      while drainage is usually necessary for the treatment, which can be done by
      transrectal, transperineal and transurethral route. 

PMID- 24085241
TI  - Impact of failed response to novel agent induction in autologous stem cell
      transplantation for multiple myeloma.
AB  - The aim of this study was to evaluate the impact of the response to induction
      therapy on the long-term prognosis of multiple myeloma (MM) after autologous stem
      cell transplantation (ASCT) in the era of novel agents (NAs). A total of 171
      patients who were newly diagnosed with MM and underwent early ASCT were analyzed.
      One hundred ten had a NA-based induction therapy, and 61 patients had a non-NA
      based induction therapy. After a median follow-up of 45.4 months, the 4-year
      overall survival (OS) and progression-free survival (PFS) from transplantation
      were 60.5 and 25.5 %, respectively, for the NA-based induction group and 54.6 and
      15.6 %, respectively, for the non-NA-based induction group. Multivariate analyses
      revealed that the patients who had NA-based induction had a significantly shorter
      OS (P < 0.001) and PFS (P < 0.001) when at least a partial response (PR) was not
      achieved. In patients who did not receive NAs before ASCT, lack of at least a PR
      to induction therapy was not associated with a survival disadvantage. These
      findings suggest that, unlike pretransplantation induction before NAs, patients
      who do not respond to induction treatment using NAs may not derive a benefit from
      ASCT. The relevance of induction failure differs for corticosteroid- and NA-based
      induction.

PMID- 24085242
TI  - Low doses of ionizing radiation induce immune-stimulatory responses in isolated
      human primary monocytes.
AB  - The health effects arising from exposure to low doses of ionizing radiation are
      of particular concern, mainly due to the increased application of diagnostic and
      therapeutic X-ray modalities. The mechanisms behind the cell and tissue responses
      to low doses remain to be elucidated. Accumulating evidence suggests that low
      doses of ionizing radiation induce activation of the immune response; however,
      the processes involved have yet to be adequately investigated. Monocytes are key
      players in the induction of an immune response. Within the context of this study,
      we investigated the activation of toll-like receptors (TLRs), mitogen-activated
      protein kinases (MAPKs) and NF-kappaB signaling in isolated human primary
      monocytes in response to low doses (0.05 and 0.1 Gy) and a high dose (1 Gy) of
      ionizing radiation. Using quantitative RT-PCR and ELISA techniques, our results
      showed a positive regulation of TLR signaling in response to low doses but a less
      significant response at high doses. This activation was demonstrated via the
      activation of TLR signaling molecules (HMGB1, TLR4, TLR9, MyD88 and IRAK1).
      Furthermore, and in contrast to the high dose, the low doses showed increased
      phosphorylation levels of the protein IkappaBalpha, and therefore positive
      signaling of the NF-kappaB pathway. This result denotes pro-survival and pro
      inflammatory responses. Additionally, MAPKs were activated in response to 0.05
      Gy, while 0.1 and 1 Gy showed a downregulatory trend that may be related to
      activation of the PF4 gene. On the other hand, there was highly significant
      involvement of activated p53 and damaged genes in response to high but not low
      doses. In conclusion, this study addressed the need to re-evaluate health risks
      arising from exposure to low doses of ionizing radiation, particularly in view of
      the accumulating evidence reporting inflammatory and oncogenic consequences from
      these exposures. 

PMID- 24085243
TI  - In-depth bioinformatic analysis of lung cancer-associated microRNA targets.
AB  - Lung cancer (LC) is the leading cause of cancer-related mortality worldwide.
      However, few studies of its specific mechanisms useful for diagnosis or treatment
      exist. microRNAs (miRNAs) present one mechanism through which genes with diverse
      functions on multiple pathways can be simultaneously regulated at the post
      transcriptional level. However, LC-associated pathways targeted by LC-related
      miRNAs (LC-miRNAs) remain completely unknown. In the present study, we
      investigated 8 LC-miRNAs previously identified as regulators in three molecular
      subtypes of LC. The results showed that LC-miRNAs may post-transcriptionally
      function mainly through manipulating the expression of nucleic acid binding
      proteins and transcription factors, and target genes for the LC-miRNAs were most
      prominently predicted to function in regulation of transcription. Our analysis
      also highlighted the potential of these LC-miRNAs to regulate the cell
      differentiation, proliferation, endocytosis and migration signaling logically
      required to cause an LC cell mainly through five canonical pathways (PI3K-Akt
      signaling pathway, pathways in cancer, MAPK signaling pathway, HTLV-I infection
      and focal adhesion). These findings may form a useful basis for potential future
      development of novel LC therapeutic treatments. 

PMID- 24085244
TI  - Prognostic significance of free-floating right heart thromboemboli in acute
      pulmonary embolism: results from the Italian Pulmonary Embolism Registry.
AB  - The exact prevalence of mobile right heart thromboemboli (RHTh) in patients with
      pulmonary embolism (PE) is unknown, depending upon PE severity and the use of
      early echocardiography. Similarly, the mortality rate is variable, though RHTh
      detection appears to substantially increase the risk of death in patients with
      PE. The aim of this study was to assess the prevalence of RHTh in different risk
      categories in a wide series of patients with PE, and to analyse the effect of
      RHTh on in-hospital mortality. Among 1,716 patients enrolled in the Italian
      Pulmonary Embolism Registry, 1,275 (13.3% at high risk, 59.3% at intermediate
      risk and 27.4% at low risk) had echocardiography within 48 hours from hospital
      admission and entered the study. Overall, RHTh were detected in 57 patients
      (4.5%, at admission echocardiography in 88%): in 27/169 (16%) high-risk, in
      29/756 (3.8%) intermediate-risk and 1/350 (0.3%) low-risk patients, respectively.
      At multivariate analysis, only advanced age (odds ratio [OR] 1.61, 95% confidence
      [CI] 1.27-2.03, p<0.0001), high-risk category (OR vs low-risk category 37.82, 95%
      CI 11.26-127.06, p<0.0001) and recurrent PE (OR 45.92, 95%CI 15.19-139.96,
      p<0.0001) showed a statistically significant effect on mortality. The presence of
      RHTh significantly increased the risk of dying (OR 3.89, 95%CI 1.98-7.67,
      p=0.0001) at univariate analysis, but this result was not mantained in the
      multivariate model (OR 1.64, 95%CI 0.75-3.60, p=0.216). In conclusion, though
      patients with RHTh had a more severe presentation of PE, this study did not
      detect an association between RHTh and prognosis. 

PMID- 24085245
TI  - The first "Kuhn verdazyl" ligand and comparative studies of its PdCl2 complex
      with analogous 6-oxoverdazyl ligands.
AB  - The synthesis and characterization of two new N,N'-diarylverdazyl radical ligands
      and their corresponding PdCl2 complexes are described. One of the two radicals is
      of the "Kuhn verdazyl" structure type and was made by adaptation of standard
      synthetic procedures for this class of verdazyl. The N,N'-diphenyl-6-oxoverdazyl
      was prepared by hydrolysis of a related tetrazane; the resulting N,N'
      diphenylcarbohydrazide was condensed with pyridinecarboxaldehyde and then
      oxidized to the verdazyl according to standard protocols. Square planar PdCl2
      complexes of both verdazyls were prepared by reactions of the radicals with PdCl2
      in acetonitrile solution. The structural, spectroscopic, and electrochemical
      properties of the new verdazyl ligands and their Pd complexes are reported;
      generally the distinct ligand-centred properties associated with each verdazyl
      type carry over into the properties of the complexes. The electrochemical studies
      reveal ligand-centred oxidation and reduction processes; despite the minimal
      extent of spin delocalization onto Pd in the metal complexes, large shifts in
      oxidation and reduction potentials (relative to those of the free verdazyl
      ligands) are discussed. 

PMID- 24085246
TI  - Cerebrospinal fluid biomarkers of Alzheimer's disease in Chinese patients: a
      pilot study.
AB  - In view of the paucity of data on cerebrospinal fluid (CSF) biomarkers in Chinese
      patients, we evaluated the validity of tau, phosphorylated tau 181 (p-tau-181),
      amyloid beta 42 (Abeta42), and Abeta40 proteins in Chinese patients with
      Alzheimer's disease (AD). We recruited 24 patients with AD, 12 nondemented
      controls, and 12 patients with non-AD dementia. We found the CSF levels of
      Abeta42, tau, p-tau, Abeta42-tau, and Abeta42-p-tau ratios, except the Abeta40
      protein level, were significantly different among the 3 groups of patients.
      Patients with AD had higher levels of CSF tau and p-tau but lower levels of
      Abeta42 proteins, Abeta42-tau, and Abeta42-p-tau ratios than the nondemented
      controls. In the diagnosis of AD versus nondementia, the sensitivity and
      specificity of the ratios of Abeta42-tau and Abeta42-p-tau were 96% and 83%
      versus 92% and 83%, respectively. Only the Abeta42-p-tau ratio showed
      satisfactory sensitivity and specificity in the diagnosis of AD versus other
      dementia. 

PMID- 24085247
TI  - The impact of mild cognitive impairment on sexual activity.
AB  - OBJECTIVE: The aim of this study was to identify the unique impact of mild
      cognitive impairment (MCI) on sexual activity among older adults. METHODS: Data
      for the study were drawn from a national survey entitled the "Determinants of
      Wellness among Older Malaysians: A Health Promotion Perspective" conducted in
      2010. RESULTS: According to the Mini-Mental State Examination education-adjusted
      cutoff points, 15.6% of the 1046 respondents were identified as having MCI. Older
      adults with MCI had a significantly lower level of sexual activity than the
      healthy cognitive group (chi-square = 50.20, P < .001, 32.5% vs 62.3%). The
      results of 3-step hierarchical logistic regression model revealed that MCI is
      significantly associated with decreased sexual activity in community-dwelling
      older adults, over and beyond demographic factors, and age-related medical
      conditions affecting sexual activity (odds ratio 0.33, P < .001, 95% confidence
      interval 0.23-0.49). CONCLUSION: Findings from the present study support the
      significant role of cognitive functioning to perform sexual activity in later
      life.

PMID- 24085248
TI  - Correction for a potentially biased item on the Mattis dementia rating scale.
AB  - The Mattis Dementia Rating Scale (MDRS) is a multidimensional cognitive measure
      popular with clinicians for its brevity, diagnostic validity, and utility in
      monitoring impairment severity. In spite of the test's significant value, one
      task can cause discomfort because the patient is asked to name items the examiner
      is wearing. This task also creates possible cultural bias and standardization
      issues. We studied 102 MDRS profiles that included this item. Adjusted scores
      were calculated by giving all patients full credit for the apparel-naming item.
      The average adjustment was just one point, and the resulting dementia-severity
      ratings remained unchanged in 97% of the patients. These results show that
      administration of the item can be defensibly skipped if there is concern about
      its appropriateness with an individual patient. The adjusted scores provide a
      viable and fair alternative that preserves the psychometric properties of this
      useful instrument. 

PMID- 24085249
TI  - Registration of Alzheimer's disease in Taiwan: patient and informant.
AB  - BACKGROUND: To obtain updated data of patients with Alzheimer's disease (AD) and
      their informants in Taiwan with the aim of fostering and supporting collaborative
      research. METHODS: In total, 691 patients with the diagnosis of AD were recruited
      at 6 sites in Taiwan. The Uniform Data Set (UDS; form A) was administrated.
      RESULTS: The mean age of the patients with AD was 79.3 +/- 7.7 years and the mean
      age of informants was 57.5 +/- 13.7 years. In all, 69% of the informants lived
      with patients and 77% of patients lived with spouse, partner, or children; 11%
      had 1 sibling with dementia, 1.8% had 2 siblings with dementia, and 0.5% had 3 or
      more siblings with dementia. CONCLUSION: We have reported the updated status of
      AD in Taiwan through a UDS that will foster future collaboration among countries
      using UDS. The updated information of patients with AD and their informants will
      direct the future care of AD in Taiwan.

PMID- 24085250
TI  - What is family-centered care for nursing home residents with advanced dementia?
AB  - To understand family members' perspectives on person- and family-centered end-of
      life care provided to nursing home (NH) residents with advanced dementia, we
      conducted a qualitative follow-up interview with 16 respondents who had
      participated in an earlier prospective study, Choices, Attitudes, and Strategies
      for Care of Advance Dementia at End of Life (CASCADE). Family members of NH
      residents (N = 16) with advanced dementia participated in semistructured
      qualitative interviews that inquired about overall NH experience, communication,
      surrogate decision making, emotional reaction, and recommendations for
      improvement. Analysis identified 5 areas considered important by family members:
      (1) providing basic care; (2) ensuring safety and security; (3) creating a sense
      of belonging and attachment; (4) fostering self-esteem and self-efficacy; and (5)
      coming to terms with the experience. These themes can provide a framework for
      creating and testing strategies to meet the goal of person- and family-centered
      care. 

PMID- 24085252
TI  - Importance of hypertension and social isolation in causing sleep disruption in
      dementia.
AB  - This study aimed to determine the effects of diabetes mellitus (DM), hypertension
      (HT), heart disease, social isolation, and sociodemographic factors on sleep in
      the elderly patients with dementia. Samples included 1210 noninstitutionalized,
      Malaysian elderly patients with dementia. The multiple logistic regression
      analysis was applied to estimate the risk of sleep disturbances among
      respondents. Approximately 41% of the patients experienced sleep problems. The
      results showed that age (odds ratio [OR] = 1.02), social isolation (OR = 1.33),
      and HT (OR = 1.53) significantly increased sleep disruption in respondents (P
      <.05). Furthermore, education (OR =.63) and non-Malay ethnicity (OR = 0.63)
      significantly decreased sleep problems (P <.05). It was found that DM, heart
      disease, sex differences, and marital status were not significant predictors of
      sleep disturbances (P >.05). It was concluded that age, social isolation, and HT
      increased sleep disruption but education and ethnic non-Malay reduced the risk of
      sleep problems. Moreover, HT was the most important variable to increase sleep
      disturbances in the elderly patients with dementia. 

PMID- 24085251
TI  - A pilot of an intervention delivered to Chinese- and Spanish-speaking carers of
      people with dementia in Australia.
AB  - There are limited language- and culture-specific support programs for carers of
      people with dementia living in Australia. A group intervention for use with
      Chinese and Spanish speakers in the United States was adapted to the Australian
      context, and a pilot study was undertaken with these 2 communities. The
      intervention is based on a cognitive behavioral therapy approach and was
      delivered by bilingual health professionals. The adapted material comprised 7
      sessions, spanning 2 hours in duration. All 22 participants completed the
      Depression Anxiety and Stress Scale-Short form (DASS-21) pre- and
      postintervention. A significant decrease in depression, anxiety, and stress was
      observed among Spanish speakers; a significant decrease in depression and anxiety
      was present among the Chinese speakers. The implications are considered in the
      context of Australia's changing aged care service system. 

PMID- 24085253
TI  - The impact of volunteer mentoring schemes on carers of people with dementia and
      volunteer mentors: a systematic review.
AB  - This systematic review aims to examine the differences and similarities between
      the various types of volunteer mentoring (befriending, mentoring and peer
      support) and to identify the benefits for carers and volunteers. Literature
      searching was performed using 8 electronic databases, gray literature, and
      reference list searching of relevant systematic reviews. Searches were carried
      out in January 2013. Four studies fitted the inclusion criteria, with 3
      investigating peer support and 1 befriending for carers. Quantitative findings
      highlighted a weak but statistically significant (P =.04) reduction in depression
      after 6 months of befriending. Qualitative findings highlighted the value carers
      placed on the volunteer mentors' experiential similarity. Matching was not
      essential for the development of successful volunteer mentoring relationships. In
      conclusion, the lack of need for matching and the importance of experiential
      similarity deserve further investigation. However, this review highlights a lack
      of demonstrated efficacy of volunteer mentoring for carers of people with
      dementia. 

PMID- 24085254
TI  - Hippocampal and mesial temporal sclerosis in early-onset frontotemporal lobar
      degeneration versus Alzheimer's disease.
AB  - Hippocampal sclerosis (HS) and mesial temporal sclerosis (MTS) may occur with
      frontotemporal lobar degeneration (FTLD) and Alzheimer's disease (AD) as well as
      with normal aging. Prior studies suggest that HS/MTS may be more closely
      associated with FTLD but have not directly compared the prevalence and clinical
      characteristics of HS/MTS between neuropathologically confirmed early-onset (age
      <= 65) cohorts of FTLD and AD. We identified patients with early-onset FTLD (n =
      136) and AD (n = 267) from National Alzheimer's Center Consortium databases and
      compared neuropathological and clinical data between these 2 groups. The FTLD
      group had a significantly higher prevalence of HS/MTS than that of the AD group.
      However, HS/MTS was associated with increasing age and memory impairment in the
      AD group but not in the FTLD group. These findings are consistent with the
      hypothesis that HS/MTS in FTLD occurs as part of the primary pathological
      process, rather than as a secondary, nonspecific effect of aging on memory and
      hippocampal function. 

PMID- 24085255
TI  - Implication of the nutritional and nonnutritional factors in the context of
      preservation of cognitive performance in patients with dementia/depression and
      Alzheimer disease.
AB  - It has been postulated that Alzheimer disease (AD) is a systemic process, which
      involves multiple pathophysiological factors. A combination of pharmacotherapy
      and nonpharmacological interventions has been proposed to treat AD and other
      dementia. The nonpharmacological interventions include but are not limited to
      increasing sensory input through physical and mental activities, in order to
      modify cerebral blood flow and implementing nutritional interventions such as
      diet modification and vitamins and nutraceuticals therapy to vitalize brain
      functioning. This article highlights the recent research findings regarding novel
      treatment strategies aimed at modifying natural course of the disease and
      delaying cognitive decline through simultaneous implementation of pharmacological
      and nonpharmacological modulators as standardized treatment protocols.

PMID- 24085256
TI  - The Bedford Alzheimer nursing-severity scale to assess dementia severity in
      advanced dementia: a nonparametric item response analysis and a study of its
      psychometric characteristics.
AB  - The Bedford Alzheimer Nursing-Severity Scale (BANS-S) assesses disease severity
      in patients with advanced Alzheimer's disease. Since Alzheimer is a progressive
      disease, studying the hierarchy of the items in the scale can be useful to
      evaluate the progression of the disease. Data from 164 Alzheimer's patients and
      186 patients with other dementia were analyzed using the Mokken Scaling
      Methodology to determine whether respondents can be ordered in the trait dementia
      severity, and to study whether an ordering between the items exist. The
      scalability of the scale was evaluated by the H coefficient. Results showed that
      the BANS-S is a reliable and medium scale (0.4<=H<0.5) for the Alzheimer group.
      All items with the exception of the item about mobility could be ordered. When
      later item was eliminated from the scale, the H coefficient decreased indicating
      that the scalability of the scale in the original form is more accurate than in
      the shorter version. For the other dementia group, the BANS-S did not fit any of
      the Mokken Scaling models because the scale was not unidimensional. In this
      group, a shorter version of the scale without the sleeping cycle item and the
      mobility item has better reliability and scalability properties than the original
      scale. 

PMID- 24085257
TI  - Innate immune responses in raccoons after raccoon rabies virus infection.
AB  - Zoonotic wildlife diseases pose significant health risks not only to their
      primary vectors but also to humans and domestic animals. Rabies is a lethal
      encephalitis caused by rabies virus (RV). This RNA virus can infect a range of
      terrestrial mammals but each viral variant persists in a particular reservoir
      host. Active management of these host vectors is needed to minimize the negative
      impacts of this disease, and an understanding of the immune response to RV
      infection aids strategies for host vaccination. Current knowledge of immune
      responses to RV infection comes primarily from rodent models in which an innate
      immune response triggers activation of several genes and signalling pathways. It
      is unclear, however, how well rodent models represent the immune response of
      natural hosts. This study investigates the innate immune response of a primary
      host, the raccoon, to a peripheral challenge using the raccoon rabies virus
      (RRV). The extent and temporal course of this response during RRV infection was
      analysed using genes predicted to be upregulated during infection (IFNs; IFN
      regulatory factors; IL-6; Toll like receptor-3; TNF receptor). We found that RRV
      activated components of the innate immune system, with changes in levels of
      transcripts correlated with presence of viral RNA. Our results suggest that
      natural reservoirs of rabies may not mimic the immune response triggered in
      rodent models, highlighting the need for further studies of infection in primary
      hosts. 

PMID- 24085258
TI  - Genetic polymorphism of matrix metalloproteinase family and chronic obstructive
      pulmonary disease susceptibility: a meta-analysis.
AB  - Matrix metalloproteinase (MMP) family is considered to be associated with chronic
      obstructive pulmonary disease (COPD) pathogenesis, however, no consistent results
      have been provided by previous studies. In this report, we performed Meta
      analysis to investigate the association between four kinds of MMP single
      nucleotide polymorphisms (SNP, MMP1 -1607 1G/2G, MMP3 -1171 5A/6A, MMP9 -1562
      C/T, MMP12 -82 A/G) and COPD risk from 21 studies including 4184 cases and 5716
      controls. Both overall and subgroup association between SNP and COPD
      susceptibility were tested. There was no evident association between MMP
      polymorphisms and COPD susceptibility in general population. On the other hand,
      subgroup analysis suggested that MMP9 -1562 C/T polymorphism was related to COPD,
      as we found that C allele carriers were at lower risk in some subgroups
      stratified by lung function, age and genotype identification method, compared
      with TT homozygotes. Our results indicated the genotype TT might be one genetic
      risk factor of severe COPD. 

PMID- 24085259
TI  - A polymorphism in a functional region of the COL5A1 gene: association with
      ultraendurance-running performance and joint range of motion.
AB  - PURPOSE: Endurance-running performance and joint range of motion (ROM) are both
      multifactorial phenotypes. A single-nucleotide polymorphism, rs172722 (C/T), in
      the COL5A1 3'-untranslated region (UTR) was shown to independently associate with
      both phenotypes. Two major functional forms of the COL5A1 3'-UTR have been
      identified and differ by 7 tightly linked polymorphisms that include rs12722 and
      a short tandem-repeat polymorphism (STRP rs71746744, -/AGGG). It has been
      proposed that STRP rs71746744 plays a role in the predicted secondary structures
      and mRNA stability of the 2 major forms of the COL5A1 3'-UTR, therefore implying
      a regulatory role. The aim of this study was to determine whether STRP rs71746744
      is independently associated with running performance and prerace sit-and-reach
      range of motion (SR ROM) in a cohort of ultramarathon road runners. METHODS: One
      hundred six (74 men and 32 women, age 22-67 y) white runners who participated in
      either the 2009 or 2011 Two Oceans 56-km ultramarathon were included in this
      cross-sectional study. Their SR ROM measurements, COL5A1 rs71746744 genotype, and
      overall race times were determined. RESULTS: COL5A1 rs71746744 was independently
      associated with running performance (P = .024) and prerace SR ROM (P = .020).
      Moreover, the AGGG/AGGG genotype was significantly overrepresented in the fastest
      and inflexible athletes compared with those with either the -/AGGG or -/-
      genotype. CONCLUSIONS: These findings provide further evidence for a relationship
      between COL5A1, running performance, and SR ROM. Further studies are needed to
      investigate the effect of this variant on the mechanical properties of connective
      tissue.

PMID- 24085260
TI  - Phase II, open-label trial to assess QTcF effects, pharmacokinetics and antitumor
      activity of afatinib in patients with relapsed or refractory solid tumors.
AB  - PURPOSE: Afatinib is an irreversible ErbB family blocker currently under
      evaluation in late-stage clinical trials. This study primarily assessed the
      cardiac safety, pharmacokinetics and antitumor activity of afatinib in cancer
      patients. METHODS: In this multicenter, Phase II, open-label, single-arm trial,
      60 patients with solid tumors who were expected to express epidermal growth
      factor receptor-1 and HER2 received oral afatinib 50 mg daily. QTcF intervals (QT
      interval corrected by the Fridericia formula) were evaluated based on
      electrocardiogram recordings time-matched with pharmacokinetic blood samples
      after single (Day 1) and continuous (Day 14; steady state) administration.
      Adverse events were classified according to the National Cancer Institute Common
      Terminology Criteria for Adverse Events (NCI CTCAE), version 3.0; antitumor
      activity was assessed using RECIST 1.0. RESULTS: There was a nonsignificant
      decrease of 0.3 ms (90 % confidence interval -2.8, 2.3; N = 49) in the mean of
      the average time-matched QTcF interval from baseline to steady state. The maximum
      plasma concentration for afatinib was seen at median tmax 3 h after both single
      dose and at steady state. No relationship between afatinib plasma concentrations
      and time-matched QTcF, QT and heart rate change was found. The overall adverse
      event profile was consistent with the known safety profile of afatinib. One
      patient demonstrated a partial response (PR) and two patients unconfirmed PRs.
      CONCLUSIONS: Afatinib had no impact on cardiac repolarization, had a manageable
      safety profile and demonstrated antitumor activity in this uncontrolled study.

PMID- 24085261
TI  - Investigation into CYP3A4-mediated drug-drug interactions on midostaurin in
      healthy volunteers.
AB  - PURPOSE: Midostaurin (PKC412), a multitargeted tyrosine kinase inhibitor that
      targets FMS-related tyrosine kinase 3 and KIT, is in clinical trials for the
      treatment for acute myeloid leukemia and advanced systemic mastocytosis. In vitro
      studies showed that midostaurin is predominantly metabolized by cytochrome P450
      3A4 (CYP3A4) and that midostaurin inhibits and/or induces the same enzyme. Here,
      we address the clinical relevance of CYP3A4-related drug-drug interactions with
      midostaurin as either a "victim" or "perpetrator." METHODS: Three phase I studies
      in healthy volunteers evaluated the effects of a CYP3A4 inhibitor (ketoconazole
      400 mg daily for 10 days) or CYP3A4 inducer (rifampicin 600 mg daily for 14 days)
      on concentrations of midostaurin and its metabolites following a single 50-mg
      dose of midostaurin and the effects of midostaurin as a single dose (100 mg) and
      multiple doses (50 mg twice daily) on midazolam (a sensitive CYP3A4 probe)
      concentration. The plasma concentrations of midostaurin and its 2 active
      metabolites, CGP62221 and CGP52421, were determined using a sensitive liquid
      chromatography/tandem mass spectrometry method. RESULTS: Inhibition of CYP3A4 by
      ketoconazole increased midostaurin exposure more than tenfold, and induction of
      CYP3A4 by rifampicin decreased midostaurin exposure by more than tenfold.
      Midostaurin did not appreciably affect the concentrations of midazolam or its
      metabolite, 1'-hydroxymidazolam, at single or multiple doses. CONCLUSION: The
      pharmacokinetics of midostaurin and its metabolites was affected substantially by
      ketoconazole and rifampicin, suggesting that midostaurin is a sensitive CYP3A4
      substrate. Midostaurin did not appear to inhibit or induce CYP3A4 in vivo.

PMID- 24085262
TI  - The VEGF pathway in lung cancer.
AB  - INTRODUCTION: Lung cancer is a disease whose prognosis has remained poor in the
      last decades. Recent advances in the understanding of the molecular pathways
      behind this disease have revealed several mediators of important tumor functions.
      One of these functions is angiogenesis, which is considered essential for tumor
      growth and propagation, and a key mediator promoting this process is the vascular
      endothelial growth factor (VEGF). In lung cancer, VEGF plays a significant role
      in establishing a vascular supply within the tumor. Thus, a new class of drugs
      has emerged, targeting its pathway, which has offered substantial, albeit small,
      improvements in patient prognosis. AREAS COVERED: The VEGF pathway and its role
      in a multitude of different human cancers are presented at first. We then proceed
      by analyzing its importance in lung cancer and exploring the therapeutic benefits
      achieved by its targeting, which set new goals for the future. EXPERT OPINION:
      Today, the VEGF pathway remains an attractive target for anticancer treatment,
      and the way forward requires detection of predictive markers and efforts for a
      more complete angiogenic blockade.

PMID- 24085263
TI  - Antitumor effect of 1, 8-cineole against colon cancer.
AB  - Several essential oils possess pharmacological effects. Among the various
      constituents of essential oils, 1, 8-cineole has been shown to possess
      pharmacological effects such as anti-bacterial and anti-inflammatory effects. The
      effect of 1, 8-cineole on human colorectal cancer cells, however, has not
      reported previously. In this study, we have investigated the anti-proliferative
      effect of 1, 8-cineole on human colon cancer cell lines HCT116 and RKO by WST-8
      and BrdU assays. The cytotoxicity of 1, 8-cineole was investigated by LDH
      activity and TUNEL staining. The mechanism of apoptosis by 1, 8-cineole was
      determined by western blot analyses. In in vivo study, RKO cells were injected
      into the SCID mice and the effect of 1, 8-cineole was investigated. Specific
      induction of apoptosis, not necrosis, was observed in human colon cancer cell
      lines HCT116 and RKO by 1, 8-cineole. The treatment with 1, 8-cineole was
      associated with inactivation of survivin and Akt and activation of p38. These
      molecules induced cleaved PARP and caspase-3, finally causing apoptosis. In
      xenotransplanted SCID mice, the 1, 8-cineole group showed significantly inhibited
      tumor progression compared to the control group. These results indicated 1, 8
      cineole suppressed human colorectal cancer proliferation by inducing apoptosis.
      Based on these studies 1, 8-cineole would be an effective strategy to treat
      colorectal cancer.

PMID- 24085266
TI  - Giant refractive-index modulation by two-photon reduction of fluorescent graphene
      oxides for multimode optical recording.
AB  - Graphene oxides (GOs) have emerged as precursors offering the potential of a cost
      effective and large-scale production of graphene-based materials. Despite that
      their intrinsic fluorescence property has already brought interest of researchers
      for optical applications, to date, refractive-index modulation as one of the
      fundamental aspects of optical properties of GOs has received less attention.
      Here we reported on a giant refractive-index modulation on the order of 10(-2) to
      10(-1), accompanied by a fluorescence intensity change, through the two-photon
      reduction of GOs. These features enabled a mechanism for multimode optical
      recording with the fluorescence contrast and the hologram-encoded refractive
      index modulation in GO-dispersed polymers for security-enhanced high-capacity
      information technologies. Our results show that GO-polymer composites may provide
      a new material platform enabling flexible micro-/nano-photonic information
      devices. 

PMID- 24085265
TI  - The bone resorption inhibitors odanacatib and alendronate affect post
      osteoclastic events differently in ovariectomized rabbits.
AB  - Odanacatib (ODN) is a bone resorption inhibitor which differs from standard
      antiresorptives by its ability to reduce bone resorption without decreasing bone
      formation. What is the reason for this difference? In contrast with other
      antiresorptives, such as alendronate (ALN), ODN targets only the very last step
      of the resorption process. We hypothesize that ODN may therefore modify the
      remodeling events immediately following osteoclastic resorption. These events
      belong to the reversal phase and include recruitment of osteoblasts, which is
      critical for connecting bone resorption to formation. We performed a
      histomorphometric study of trabecular remodeling in vertebrae of estrogen
      deficient rabbits treated or not with ODN or ALN, a model where ODN, but not ALN,
      was previously shown to preserve bone formation. In line with our hypothesis, we
      found that ODN treatment compared to ALN results in a shorter reversal phase,
      faster initiation of osteoid deposition on the eroded surfaces, and higher
      osteoblast recruitment. The latter is reflected by higher densities of mature
      bone forming osteoblasts and an increased subpopulation of cuboidal osteoblasts.
      Furthermore, we found an increase in the interface between osteoclasts and
      surrounding osteoblast-lineage cells. This increase is expected to favor the
      osteoclast-osteoblast interactions required for bone formation. Regarding bone
      resorption itself, we show that ODN, but not ALN, treatment results in shallower
      resorption lacunae, a geometry favoring bone stiffness. We conclude that,
      compared to standard antiresorptives, ODN shows distinctive effects on resorption
      geometry and on reversal phase activities which positively affect osteoblast
      recruitment and may therefore favor bone formation. 

PMID- 24085267
TI  - Nitrogen-doped pyrolytic carbon films as highly electrochemically active
      electrodes.
AB  - Nitrogen-doped Pyrolytic Carbon (N-PyC) films were employed as an electrode
      material in electrochemical applications. PyC was grown by via non-catalysed
      chemical vapour deposition and subsequently functionalised via exposure to
      ammonia-hydrogen plasma. The electrochemical properties of the N-PyC films were
      investigated using the ferri/ferro-cyanide and hexaamine ruthenium(III) chloride
      redox probes. Exceptional electron transfer properties were observed and
      quantified for the N-PyC compared to the as-grown films. X-ray photoelectron
      spectroscopy confirmed the presence of nitrogen in edge plane graphitic
      configurations and the surface of the N-PyC was investigated using scanning
      electron microscopy and atomic force microscopy. The excellent electrochemical
      performance of the N-PyC, in addition to its ease of preparation, renders this
      material ideal for applications in electrochemical sensing.

PMID- 24085268
TI  - Cystometric parameters and the activity of signaling proteins in association with
      the compensation or decompensation of bladder function in an animal experimental
      model of partial bladder outlet obstruction.
AB  - We conducted this study to determine whether the degree of detrusor contractility
      is associated with the compensation or decompensation of bladder function
      depending on the residual volume (RV) during the first two weeks after the onset
      of partial bladder outlet obstruction (BOO). Moreover, we also examined whether
      the degree of the phosphorylation and expression of signaling proteins [AMP
      activated kinase (AMPK), extracellular signal-regulated protein kinases 1 and 2
      (ERK1/2) and protein kinase C (PKC)] is associated with the prevalence of
      compensation or decompensation of bladder function. Twenty-seven female Sprague
      Dawley (SD) rats were randomly assigned to either the sham-operated group (n=7)
      or the group with partial bladder outlet obstruction (BOO) (n=20). We then
      measured cystometric parameters from three reproducible micturition cycles and
      averaged the results for a comparison between the two groups. Based on a cut-off
      value of a mean RV% of 25%, we subdivided our experimental animals into two
      subgroups: the subgroup with bladder compensation (mean RV%, <25%) and the
      subgroup with bladder decompensation (mean RV%, >25%). Our results indicated that
      the degree of detrusor overactivity (DO) was associated with the compensation or
      decompensation of bladder function depending on the RV during the first two weeks
      after the onset of BOO in an animal experimental model of partial BOO. Moreover,
      we also demonstrate that AMPK and ERK1/2 are involved in the compensation or
      decompensation of bladder function. Furthermore, our results suggest that PKC is
      not involved in two-phase bladder contraction. Alterations in the activities of
      signaling proteins, such as AMPK and ERK1/2 may prove to be helpful in the
      treatment of patients with voiding difficulty. 

PMID- 24085269
TI  - Phosphine-substituted sterically encumbered pyrrolyl ligands - synthesis and
      reactivity studies.
AB  - The sterically encumbered pyrrolyl KPyr(tBu2) (1-K, Pyr(tBu2) = 2,5-(Me3C)2C4H2N)
      reacts with PCl3, (iPr)2PCl and Ph2PCl exclusively at the C3-position to yield a
      series of phosphine-substituted pyrroles HPyr(tBu2R) (R = PCl2 (2-H), (iPr)2P (4
      H) and Ph2P (5-H)). Pyrrole 2-H can further be functionalized with MeLi (3
      equiv.) to yield LiPyr(tBu2PMe2) (3-Li). The coordination chemistry of these
      phosphine-substituted pyrroles was explored and the resulting complexes were
      characterized by various spectroscopic techniques and in some cases using single
      crystal X-ray diffraction. The neutral pyrroles 4-H and 5-H react cleanly with
      [Mo(CO)6] to form the kappaP-coordinate complexes 4-H-Mo(CO)5 and 5-H-Mo(CO)5,
      respectively. IR spectroscopy of these complexes shows that C3-substitution
      barely changes the pi-acceptor properties of the phosphine moiety. The eta(5)
      coordination was achieved when pyrrolides 4-K and 5-K were reacted with
      [Mn(CO)5Br] to give 4-Mn(CO)3 and 5-Mn(CO)3, respectively. The energy of the
      HOMOs in these three legged-piano stool complexes decreases on PPh2-substitution
      (5-Mn(CO)3) stabilizing the Mn-CO bonds, whereas the inverse effect is noticed
      for P(iPr)2-substitution (4-Mn(CO)3). 

PMID- 24085270
TI  - Porcine intestinal mast cells. Evaluation of different fixatives for
      histochemical staining techniques considering tissue shrinkage.
AB  - Staining of mast cells (MCs), including porcine ones, is critically dependent
      upon the fixation and staining technique. In the pig, mucosal and submucosal MCs
      do not stain or stain only faintly after formalin fixation. Some fixation methods
      are particularly recommended for MC staining, for example the fixation with
      Carnoy or lead salts. Zinc salt fixation (ZSF) has been reported to work
      excellently for the preservation of fixation-sensitive antigens. The aim of this
      study was to establish a reliable histological method for counting of MCs in the
      porcine intestinum. For this purpose, different tissue fixation and staining
      methods that also allow potential subsequent immunohistochemical investigations
      were evaluated in the porcine mucosa, as well as submucosa of small and large
      intestine. Tissues were fixed in Carnoy, lead acetate, lead nitrate, Zamboni and
      ZSF and stained subsequently with either polychromatic methylene blue, alcian
      blue or toluidine blue. For the first time our study reveals that ZSF, a heavy
      metal fixative, preserves metachromatic staining of porcine MCs. Zamboni fixation
      was not suitable for histochemical visualization of MCs in the pig intestine. All
      other tested fixatives were suitable. Alcian blue and toluidine blue co-stained
      intestinal goblet cells which made a prima facie identification of MCs difficult.
      The polychromatic methylene blue proved to be the optimal staining. In order to
      compare MC counting results of the different fixation methods, tissue shrinkage
      was taken into account. As even the same fixation caused shrinkage-differences
      between tissue from small and large intestine, different factors for each single
      fixation and intestinal localization had to be calculated. Tissue shrinkage
      varied between 19% and 57%, the highest tissue shrinkage was found after fixation
      with ZSF in the large intestine, the lowest one in the small intestine after lead
      acetate fixation. Our study emphasizes that MC counting results from data using
      different fixation techniques can only be compared if the respective study
      immanent shrinkage factor has been determined and quantification results are
      adjusted accordingly. 

PMID- 24085271
TI  - Successful triple immunoenzymatic method employing primary antibodies from same
      species and same immunoglobulin subclass.
AB  - Protocols for immunohistochemical (IHC) detection of multiple antigens in the
      same tissue sections have been developed using primary antibodies directly
      conjugated to different enzymes or fluorochromes, or ones that have been raised
      in different species, or from different immunoglobulin (Ig) classes or
      subclasses. For antibodies lacking such dissimilarities, very few proposals have
      been published with varying degrees of generalizability. In this report we
      present a successful triple IHC protocol engaging three unconjugated monoclonal
      primary antibodies raised in the same species and of the same Ig subclass.
      Compared to other methods, our results showed that denaturation of the preceding
      reaction complex by microwave heating, combined with additional suppression of
      enzyme activity, enabled the detection of all three reactions by using the same
      detection system, with no cross reaction observed. Moreover, expression patterns
      of each of the three antigens in the triple stained sections, was found to be
      similar to the pattern observed when single staining was performed. Unlike
      previous reports, no damage of targeted antigens or tissues did occur following
      this protocol. Furthermore, the contrast of the colors employed was investigated
      by computerized color deconvolution, and the three reactions products were
      successfully separated into three individual images that could be used for
      further objective quantification. 

PMID- 24085272
TI  - In vitro reparative dentin: a biochemical and morphological study.
AB  - In this study, starting from human dental pulp cells cultured in vitro, we
      simulated reparative dentinogenesis using a medium supplemented with different
      odontogenic inductors. The differentiation of dental pulp cells in odontoblast
      like cells was evaluated by means of staining, and ultramorphological,
      biochemical and biomolecular methods. Alizarin red staining showed mineral
      deposition while transmission electron microscopy revealed a synthesis of
      extracellular matrix fibers during the differentiation process. Biochemical
      assays demonstrated that the differentiated phenotype expressed odontoblast
      markers, such as Dentin Matrix Protein 1 (DMP1) and Dentin Sialoprotein (DSP), as
      well as type I collagen. Quantitative data regarding the mRNA expression of DMP1,
      DSP and type I collagen were obtained by Real Time PCR. Immunofluorescence data
      demonstrated the various localizations of DSP and DMP1 during odontoblast
      differentiation. Based on our results, we obtained odontoblast-like cells which
      simulated the reparative dentin processes in order to better investigate the
      mechanism of odontoblast differentiation, and dentin extracellular matrix
      deposition and mineralization.

PMID- 24085273
TI  - Lipid droplets characterization in adipocyte differentiated 3T3-L1 cells: size
      and optical density distribution.
AB  - The 3T3-L1 cell line, derived from 3T3 cells, is widely used in biological
      research on adipose tissue. 3T3-L1 cells have a fibroblast-like morphology, but,
      under appropriate conditions, they differentiate into an adipocyte-like
      phenotype. During the differentiation process, 3T3-L1 cells increase the
      synthesis of triglycerides and acquire the behavior of adipose cells. In
      particular, triglycerides accumulate in lipid droplets (LDs) embedded in the
      cytoplasm. The number and the size distribution of the LDs is often correlated
      with obesity and many other pathologies linked with fat accumulation. The
      integrated optical density (IOD) of the LDs is related with the amount of
      triglycerides in the droplets. The aim of this study is the attempt to
      characterize the size distribution and the IOD of the LDs in 3T3-L1
      differentiated cells. The cells were differentiated into adipocytes for 5 days
      with a standard procedure, stained with Oil Red O and observed with an optical
      microscope. The diameter, area, optical density of the LDs were measured. We
      found an asymmetry of the kernel density distribution of the maximum Feret's
      diameter of the LDs with a tail due to very large LDs. More information regarding
      the birth of the LDs could help in finding the best mathematical model in order
      to analyze fat accumulation in adipocytes. 

PMID- 24085274
TI  - Active role of the predecidual-like zone in endometrial shedding in a mouse
      menstrual-like model.
AB  - Cyclic shedding of the endometrium is unique to menstruating species. The status
      of the decidua in mouse menstrual-like models seems to differ from that of the
      predecidua in humans before endometrial breakdown. The aim of this study was to
      determine how this difference in decidual status is related to endometrial
      breakdown. A mouse menstrual-like model was generated by pharmacological
      progesterone withdrawal. Histomorphological analysis and reticular fiber staining
      were used to evaluate endometrial status. In situ zymography was used to
      determine the localization of active collagenase and gelatinase. The functional
      endometrial layer containing the mature decidual-like zone (MDZ) and predecidual
      like zone (PZ) underwent breakdown. The reticular fibers underwent disruption and
      fragmentation and became loose or disappeared at 12 h in the PZ, where active
      collagenase and gelatinase were limited. The reticular fibers were visibly
      reduced at 24 h in the MDZ, where active collagenase was detected. A few
      reticular fibers remained; however, the functional layer had sloughed into the
      lumen of the uterus. The results showed that reticular fibers of the PZ are
      actively degraded during endometrial shedding. 

PMID- 24085275
TI  - Simultaneous ultrastructural analysis of fluorochrome-photoconverted
      diaminobenzidine and gold immunolabelling in cultured cells.
AB  - Diaminobenzidine photoconversion is a technique by which a fluorescent dye is
      transformed into a stably insoluble, brown, electrondense signal, thus enabling
      examination at both bright field light microscopy and transmission electron
      microscopy. In this work, a procedure is proposed for combining photoconversion
      and immunoelectron microscopy: in vitro cell cultures have been first submitted
      to photoconversion to analyse the intracellular fate of either fluorescent
      nanoparticles or photosensitizing molecules, then processed for transmission
      electron microscopy; different fixative solutions and embedding media have been
      used, and the ultrathin sections were finally submitted to post-embedding
      immunogold cytochemistry. Under all conditions the photoconversion reaction
      product and the target antigen were properly detected in the same section; Epon
      embedded, osmicated samples required a pre-treatment with sodium metaperiodate to
      unmask the antigenic sites. This simple and reliable procedure exploits a single
      sample to simultaneously localise the photoconversion product and a variety of
      antigens allowing a specific identification of subcellular organelles at the
      ultrastructural level. 

PMID- 24085276
TI  - Immunohistochemical demonstration of keratins in the epidermal layers of the
      Malayan pangolin (Manis javanica), with remarks on the evolution of the
      integumental scale armour.
AB  - Using immunohistochemistry, the study demonstrates the distribution of keratins
      (pan-keratin with CK1-8, 10, 14-16, 19; keratins CK1, 5, 6, 9, 10; hair keratins
      AE13, AE14) in the epidermis of the Malayan pangolin (Manis javanica). A varying
      reaction spectrum was observed for pan-keratin, with body region-dependent
      negative to very strong reaction intensities. The dorsolateral epidermis
      exhibited positive reactions only in its vital layers, whereas the abdominal
      epidermis showed strong positive reactions in the soft two outer strata. The
      single acidic and basic-to-neutral (cyto)keratins produced clear variations
      compared to the pan-keratin tinging. E.g., CK1 appeared in all epidermal layers
      of both body regions, except for the ventral stratum corneum, whereas CK5, 6, 9,
      10 were restricted to the soft ventral epidermis. Here, distinctly positive
      reactions were confined to the stratum granulosum, except for CK6 that appeared
      in the soft stratum corneum. A different staining pattern was obvious for the
      hair keratins, i.e., positive reactions of AE13 concentrated only in the granular
      layer of the dorsal epidermis. In the abdominal epidermis, remarkable tinging for
      AE14 was visible in the stratum basale, decreasing toward the corneal layer, but
      was also found in the outer root sheath cells of the hair follicles in the
      ventral body part. Our findings are discussed related to the evolution of the
      horny dorsal scales of the pangolin, which may have started from the tail root,
      projecting forward to the head. 

PMID- 24085277
TI  - Continuous cyclic mechanical tension increases ank expression in endplate
      chondrocytes through the TGF-beta1 and p38 pathway.
AB  - The normal ANK protein has a strong influence on anti-calcification. It is known
      that TGF-beta1 is also able to induce extracellular inorganic pyrophosphate
      (ePPi) elaboration via the TGF-beta1-induced ank gene expression and the mitogen
      activated protein kinase (MAPK) signaling acts as a downstream effector of TGF
      beta1. We hypothesized that the expression of the ank gene is regulated by
      mechanics through TGF-beta1-p38 pathway. In this study, we investigated the
      mechanism of short-time mechanical tension-induced ank gene expression. We found
      that the continuous cyclic mechanical tension (CCMT) increased the ank gene
      expression in the endplate chondrocytes, and there was an increase in the TGF
      beta1 expression after CCMT stimulation. The ank gene expression significantly
      increased when treated by TGF-beta1 in a dose-dependent manner and decreased when
      treated by SB431542 (ALK inhibitor) in a dose-dependent manner. Our study results
      indicate that CCMT-induced ank gene expressions may be regulated by TGF-beta1 and
      p38 MAPK pathway. 

PMID- 24085278
TI  - dCTP pyrophosphohydrase exhibits nucleic accumulation in multiple carcinomas.
AB  - Nucleoside triphosphate pyrophosphohydrolase (NTP-PPase) functions as one of the
      mechanisms to guarantee the fidelity of DNA replication through the cleavage of
      non-canonical nucleotides into di- or monophosphates. Human NTP-PPase is poorly
      understood and investigated. In the present study, by using tissue microassays
      with the paired cancer and adjacent regions, we found that with the prevalent
      expression of dCTP pyrophosphohydrase (DCTPP1) in the cytosol and nucleus in
      tumors investigated, DCTPP1 was inclined to accumulate in the nucleus of cancer
      cells compared to the paired adjacent tissue cells in multiple carcinoma
      including lung, breast, liver, cervical, gastric and esophagus cancer. More
      significantly, the higher DCTPP1 expression in the nucleus of lung, gastric and
      esophagus cancer cells was associated with histological subtypes. The nucleic
      accumulation of DCTPP1 was apparently observed as well when cancer cell line MCF
      7 was treated with H2O2 in vitro. Considering the roles of DCTPP1 on restricting
      the concentration of non-canonical nucleotides in the nucleotide pool,
      accumulation of DCTPP1 in the nucleus of cancer cells might suffice for
      maintaining the proper DNA replication in order to fulfill the requirement for
      the survival and proliferation of tumor cells. 

PMID- 24085286
TI  - Core-shell structured alpha-Fe2O3@TiO2 nanocomposites with improved
      photocatalytic activity in the visible light region.
AB  - The core-shell structured Fe2O3@TiO2 nanocomposites prepared via a
      heteroepitaxial growth route using the Fe2O3 spindle as a hard template display
      improved photocatalytic degradation activity for Rhodamine B dye under visible
      light irradiation. The ratio of alpha-Fe2O3 : TiO2 in the alpha-Fe2O3@TiO2 core
      shell nanocomposites can be tuned by etching the alpha-Fe2O3 core via controlling
      the concentration of HCl and etching time. An appropriate concentration of the
      Fe2O3 core could effectively induce a transition of the optical response from the
      UV to the visible region and decrease the recombination rate of photogenerated
      electrons and the holes of the core-shell structured catalyst, greatly
      contributing to the enhancement of visible light response and visible light
      photocatalytic activity of the Fe2O3@TiO2 catalysts. It is revealed that the
      optical response and photocatalytic performance of the core-shell alpha
      Fe2O3@TiO2 nanocomposites can be tuned by adjusting the molar ratio of Fe2O3 :
      TiO2 of the alpha-Fe2O3@TiO2 nanocomposites. The alpha-Fe2O3@TiO2 core-shell
      nanocomposite with an optimal molar ratio of 7% for Fe2O3 : TiO2 exhibits the
      best photocatalytic performance under visible light irradiation. It is shown that
      the Fe2O3/TiO2 heterojunction structure is responsible for the efficient visible
      light photocatalytic activity. As the concentration of Fe2O3 is high, Fe(3+) ions
      will act as recombination centres of the photogenerated electrons and holes. The
      present core-shell Fe2O3@TiO2 nanoparticles displaying enhanced photodegradation
      activity could find potential applications as photocatalysts for the abatement of
      various organic pollutants. 

PMID- 24085287
TI  - Anti-apoptotic effect of clusterin on cisplatin-induced cell death of
      retinoblastoma cells.
AB  - Clusterin is a cytoprotective chaperone protein that is known to protect various
      retinal cells. It was also reported to be overexpressed in several types of
      malignant tumors, whose chemoresistance correlates with the expression of
      clusterin. Herein, we investigated the effect of clusterin on cisplatin-induced
      cell death of retinoblastoma cells. Firstly, evaluation of clusterin expression
      demonstrated that it was highly expressed in human retinoblastoma tissues and
      cell lines (SNUOT-Rb1 and Y79) particularly in the area between viable cells
      around vessels and necrotic zones in the relatively avascular area in human
      retinoblastoma tissues. Furthermore, the effects of cisplatin on retinoblastoma
      cells were evaluated. Cisplatin (1 ug/ml) significantly affected cell viability
      of SNUOT-Rb1 cells by inducing caspase-3-dependent apoptosis. Notably, the cell
      death due to cisplatin was prevented by 5 ug/ml of clusterin administered 4 h
      prior to cisplatin treatment by inhibiting cisplatin-induced apoptosis.
      Furthermore, overexpression of clusterin exerted its anti-apoptotic effect on
      cisplatin-induced apoptosis, and effectively prevented cisplatin-induced cell
      death. These data suggest that clusterin, found to be expressed in human
      retinoblastoma, may exert anti-apoptotic effects on cisplatin-induced apoptosis
      and prevent cell death. Therefore, clusterin can contribute to cisplatin
      resistance of retinoblastoma.

PMID- 24085288
TI  - Three monoclonal antibodies against the serpin protease nexin-1 prevent protease
      translocation.
AB  - Protease nexin-1 (PN-1) belongs to the serpin family and is an inhibitor of
      thrombin, plasmin, urokinase-type plasminogen activator, and matriptase. Recent
      studies have suggested PN-1 to play important roles in vascular-, neuro-, and
      tumour-biology. The serpin inhibitory mechanism consists of the serpin presenting
      its so-called reactive centre loop as a substrate to its target protease,
      resulting in a covalent complex with the inactivated enzyme. Previously, three
      mechanisms have been proposed for the inactivation of serpins by monoclonal
      antibodies: steric blockage of protease recognition, conversion to an inactive
      conformation or induction of serpin substrate behaviour. Until now, no inhibitory
      antibodies against PN-1 have been thoroughly characterised. Here we report the
      development of three monoclonal antibodies binding specifically and with high
      affinity to human PN-1. The antibodies all abolish the protease inhibitory
      activity of PN-1. In the presence of the antibodies, PN-1 does not form a complex
      with its target proteases, but is recovered in a reactive centre cleaved form.
      Using site-directed mutagenesis, we mapped the three overlapping epitopes to an
      area spanning the gap between the loop connecting alpha-helix F with beta-strand
      3A and the loop connecting alpha-helix A with beta-strand 1B. We conclude that
      antibody binding causes a direct blockage of the final critical step of protease
      translocation, resulting in abortive inhibition and premature release of reactive
      centre cleaved PN-1. These new antibodies will provide a powerful tool to study
      the in vivo role of PN-1's protease inhibitory activity. 

PMID- 24085289
TI  - Expected value of sample information for multi-arm cluster randomized trials with
      binary outcomes.
AB  - Expected value of sample information (EVSI) measures the anticipated net benefit
      gained from conducting new research with a specific design to add to the evidence
      on which reimbursement decisions are made. Cluster randomized trials raise
      specific issues for EVSI calculations because 1) a hierarchical model is
      necessary to account for between-cluster variability when incorporating new
      evidence and 2) heterogeneity between clusters needs to be carefully
      characterized in the cost-effectiveness analysis model. Multi-arm trials provide
      parameter estimates that are correlated, which needs to be accounted for in EVSI
      calculations. Furthermore, EVSI is computationally intensive when the net benefit
      function is nonlinear, due to the need for an inner-simulation step. We develop a
      method for the computation of EVSI that avoids the inner simulation step for
      cluster randomized multi-arm trials with a binary outcome, where the net benefit
      function is linear in the probability of an event but nonlinear in the log-odds
      ratio parameters. We motivate and illustrate the method with an example of a
      cluster randomized 2 * 2 factorial trial for interventions to increase attendance
      at breast screening in the UK, using a previously reported cost-effectiveness
      model. We highlight assumptions made in our approach, extensions to individually
      randomized trials and inclusion of covariates, and areas for further
      developments. We discuss computation time, the research-design space, and the
      ethical implications of an EVSI approach. We suggest that EVSI is a practical and
      appropriate tool for the design of cluster randomized trials.

PMID- 24085290
TI  - Using tree diagrams without numerical values in addition to relative numbers
      improves students' numeracy skills: a randomized study in medical education.
AB  - BACKGROUND: Physicians and medical students may lack sufficient numeracy skills
      to make treatment decisions, interpret test results, and practice evidence-based
      medicine. We evaluated whether the use of a tree diagram without numerical values
      as an aid for numerical processing might improve students' test results when
      dealing with percentages. METHODS: A prospective randomized study was carried out
      with 102 third-year students. Participants received 3 diagnostic test problems
      and were asked to determine positive predictive values. The information in these
      tests was expressed either in (1) natural frequencies, (2) conditional
      probabilities, or (3) conditional probabilities with a tree diagram without
      numbers. RESULTS: Ninety-eight (96.1%) complete data sets could be obtained. The
      group working with natural frequencies achieved significantly higher test results
      (n = 29, mean score: 1.1, P = 0.045) than the group working with conditional
      probabilities (n = 34, mean score: 0.56). The students who were given a tree
      diagram in addition to conditional probabilities (n = 35, mean score: 1.26) also
      achieved significantly better scores than the group with conditional
      probabilities alone (P = 0.008). The difference between the group who had
      received natural frequencies and the group working with conditional probabilities
      and the tree diagram was not significant. CONCLUSIONS: We suggest the use of a
      tree diagram as a visual aid when dealing with diagnostic tests expressed in
      conditional probabilities.

PMID- 24085291
TI  - Inhibition of Snail1-DNA-PKcs protein-protein interface sensitizes cancer cells
      and inhibits tumor metastasis.
AB  - Our previous study suggested that the DNA-dependent protein kinase catalytic
      subunit (DNA-PKcs) interacts with Snail1, which affects genomic instability,
      sensitivity to DNA-damaging agents, and migration of tumor cells by reciprocal
      regulation between DNA-PKcs and Snail1. Here, we further investigate that a
      peptide containing 7-amino acid sequences (amino acids 15-21) of Snail1 (KPNYSEL,
      SP) inhibits the endogenous interaction between DNA-PKcs and Snail1 through
      primary interaction with DNA-PKcs. SP restored the inhibited DNA-PKcs repair
      activity and downstream pathways. On the other hand, DNA-PKcs-mediated
      phosphorylation of Snail1 was inhibited by SP, which resulted in decreased Snail1
      stability and Snail1 functions. However, these phenomena were only shown in p53
      wild-type cells, not in p53-defective cells. From these results, it is suggested
      that interfering with the protein interaction between DNA-PKcs and Snail1 might
      be an effective strategy for sensitizing cancer cells and inhibiting tumor
      migration, especially in both Snail1-overexpressing and DNA-PKcs-overexpressing
      cancer cells with functional p53. 

PMID- 24085292
TI  - Long-term incubation with proteasome inhibitors (PIs) induces IkappaBalpha
      degradation via the lysosomal pathway in an IkappaB kinase (IKK)-dependent and
      IKK-independent manner.
AB  - Proteasome inhibitors (PIs) have been reported to induce apoptosis in many types
      of tumor. Their apoptotic activities have been suggested to be associated with
      the up-regulation of molecules implicated in pro-apoptotic cascades such as p53,
      p21(Waf1), and p27(Kip1). Moreover, the blocking of NF-kappaB nuclear
      translocation via the stabilization of IkappaB is an important mechanism of PI
      induced apoptosis. However, we found that long-term incubation with PIs (PS-341
      or MG132) increased NF-kappaB-regulated gene expression such as COX-2, cIAP2,
      XIAP, and IL-8 in a dose- and time-dependent manner, which was mediated by
      phosphorylation of IkappaBalpha and its subsequent degradation via the
      alternative route, lysosome. Overexpression of the IkappaBalpha superrepressor
      (IkappaBalpha-SR) blocked PI-induced NF-kappaB activation. Treatment with
      lysosomal inhibitors (ammonium chloride or chloroquine) or inhibitors of
      cathepsins (Z-FF-FMK or Z-FA-FMK) or knock-down of LC3B expression by siRNAs
      suppressed PI-induced IkappaBalpha degradation. Furthermore, we found that both
      IKK-dependent and IKK-independent pathways were required for PI-induced
      IkappaBalpha degradation. Pretreatment with IKKbeta specific inhibitor, SC-514,
      partially suppressed IkappaBalpha degradation and IL-8 production by PIs.
      Blockade of IKK activity using insolubilization by heat shock (HS) and knock-down
      by siRNAs for IKKbeta only delayed IkappaBalpha degradation up to 8 h after
      treatment with PIs. In addition, PIs induced Akt-dependent inactivation of GSK
      3beta. Inactive GSK-3beta accelerated PI-induced IkappaBalpha degradation.
      Overexpression of active GSK-3beta (S9A) or knock-down of GSK-3beta delayed PI
      induced IkappaBalpha degradation. Collectively, our data demonstrate that long
      term incubation with PIs activates NF-kappaB, which is mediated by IkappaBalpha
      degradation via the lysosome in an IKK-dependent and IKK-independent manner. 

PMID- 24085293
TI  - Activated Cdc42-associated kinase 1 (Ack1) is required for tumor necrosis factor
      related apoptosis-inducing ligand (TRAIL) receptor recruitment to lipid rafts and
      induction of cell death.
AB  - TNF-related apoptosis-inducing ligand (TRAIL) holds promise for treatment of
      cancer due to its ability to selectively kill cancer cells while sparing normal
      cells. Ligand-induced translocation of TRAIL receptors (TRAIL-R) 1 and 2 (also
      called DR4 and DR5, respectively) into lipid raft membrane microdomains is
      required for TRAIL-induced cell death by facilitating receptor clustering and
      formation of the death-inducing signaling complex, yet the underlying regulatory
      mechanisms remain largely unknown. We show here that the non-receptor tyrosine
      kinase Ack1, previously implicated in the spatiotemporal regulation of the EGF
      receptor, is required for TRAIL-induced cell death in multiple epithelial cell
      lines. TRAIL triggered a transient up-regulation of Ack1 and its recruitment to
      lipid rafts along with TRAIL-R1/2. siRNA-mediated depletion of Ack1 disrupted
      TRAIL-induced accumulation of TRAIL-R1/2 in lipid rafts and efficient recruitment
      of caspase-8 to the death-inducing signaling complex. Pharmacological inhibition
      of Ack1 did not affect TRAIL-induced cell death, indicating that Ack1 acts in a
      kinase-independent manner to promote TRAIL-R1/2 accumulation in lipid rafts.
      These findings identify Ack1 as an essential player in the spatial regulation of
      TRAIL-R1/2. 

PMID- 24085295
TI  - Elucidation of molecular impediments in the alpha6 subunit for in vitro
      expression of functional alpha6beta4* nicotinic acetylcholine receptors.
AB  - Explorations into the alpha6-containing nicotinic acetylcholine receptors
      (alpha6* nAChRs) as putative drug targets have been severely hampered by the
      inefficient functional expression of the receptors in heterologous expression
      systems. In this study, the molecular basis for the problem was investigated
      through the construction of chimeric alpha6/alpha3 and mutant alpha3 and alpha6
      subunits and functional characterization of these co-expressed with beta4 or
      beta4beta3 subunits in tsA201 cells in a fluorescence-based assay and in Xenopus
      oocytes using two-electrode voltage clamp electrophysiology. Substitution of a
      small C-terminal segment in the second intracellular loop or the Phe(223) residue
      in transmembrane helix 1 of alpha6 with the corresponding alpha3 segment or
      residue was found to enhance alpha6beta4 functionality in tsA201 cells
      significantly, in part due to increased cell surface expression of the receptors.
      The gain-of-function effects of these substitutions appeared to be additive since
      incorporation of both alpha3 elements into alpha6 resulted in assembly of
      alpha6beta4* receptors exhibiting robust functional responses to acetylcholine.
      The pharmacological properties exhibited by alpha6beta4beta3 receptors comprising
      one of these novel alpha6/alpha3 chimeras in oocytes were found to be in good
      agreement with those from previous studies of alpha6* nAChRs formed from other
      surrogate alpha6 subunits or concatenated subunits and studies of other
      heteromeric nAChRs. In contrast, co-expression of this alpha6/alpha3 chimera with
      beta2 or beta2beta3 subunits in oocytes did not result in efficient formation of
      functional receptors, indicating that the identified molecular elements in alpha6
      could be specific impediments for the expression of functional alpha6beta4*
      nAChRs. 

PMID- 24085294
TI  - The prometastatic ribosomal S6 kinase 2-cAMP response element-binding protein
      (RSK2-CREB) signaling pathway up-regulates the actin-binding protein fascin-1 to
      promote tumor metastasis.
AB  - Metastasis is the leading cause of death in patients with breast, lung, and head
      and neck cancers. However, the molecular mechanisms underlying metastases in
      these cancers remain unclear. We found that the p90 ribosomal S6 kinase 2 (RSK2)
      cAMP response element-binding protein (CREB) pathway is commonly activated in
      diverse metastatic human cancer cells, leading to up-regulation of a CREB
      transcription target Fascin-1. We also observed that the protein expression
      patterns of RSK2 and Fascin-1 correlate in primary human tumor tissue samples
      from head and neck squamous cell carcinoma patients. Moreover, knockdown of RSK2
      disrupts filopodia formation and bundling in highly invasive cancer cells,
      leading to attenuated cancer cell invasion in vitro and tumor metastasis in vivo,
      whereas expression of Fascin-1 significantly rescues these phenotypes.
      Furthermore, targeting RSK2 with the small molecule RSK inhibitor FMK-MEA
      effectively attenuated the invasive and metastatic potential of cancer cells in
      vitro and in vivo, respectively. Taken together, our findings for the first time
      link RSK2-CREB signaling to filopodia formation and bundling through the up
      regulation of Fascin-1, providing a proinvasive and prometastatic advantage to
      human cancers. Therefore, protein effectors of the RSK2-CREB-Fascin-1 pathway
      represent promising biomarkers and therapeutic targets in the clinical prognosis
      and treatment of metastatic human cancers. 

PMID- 24085296
TI  - Flavonoid regulation of HCN2 channels.
AB  - The hyperpolarization-activated cyclic nucleotide-modulated (HCN) channels are
      pacemaker channels whose currents contribute to rhythmic activity in the heart
      and brain. HCN channels open in response to hyperpolarizing voltages, and the
      binding of cAMP to their cyclic nucleotide-binding domain (CNBD) facilitates
      channel opening. Here, we report that, like cAMP, the flavonoid fisetin
      potentiates HCN2 channel gating. Fisetin sped HCN2 activation and shifted the
      conductance-voltage relationship to more depolarizing potentials with a half
      maximal effective concentration (EC50) of 1.8 MUM. When applied together, fisetin
      and cAMP regulated HCN2 gating in a nonadditive fashion. Fisetin did not
      potentiate HCN2 channels lacking their CNBD, and two independent fluorescence
      based binding assays reported that fisetin bound to the purified CNBD. These data
      suggest that the CNBD mediates the fisetin potentiation of HCN2 channels.
      Moreover, binding assays suggest that fisetin and cAMP partially compete for
      binding to the CNBD. NMR experiments demonstrated that fisetin binds within the
      cAMP-binding pocket, interacting with some of the same residues as cAMP.
      Together, these data indicate that fisetin is a partial agonist for HCN2
      channels.

PMID- 24085297
TI  - Two major facilitator superfamily sugar transporters from Trichoderma reesei and
      their roles in induction of cellulase biosynthesis.
AB  - Proper perception of the extracellular insoluble cellulose is key to initiating
      the rapid synthesis of cellulases by cellulolytic Trichoderma reesei. Uptake of
      soluble oligosaccharides derived from cellulose hydrolysis represents a potential
      point of control in the induced cascade. In this study, we identified a major
      facilitator superfamily sugar transporter Stp1 capable of transporting cellobiose
      by reconstructing a cellobiose assimilation system in Saccharomyces cerevisiae.
      The absence of Stp1 in T. reesei resulted in differential cellulolytic response
      to Avicel versus cellobiose. Transcriptional profiling revealed a different
      expression profile in the Deltastp1 strain from that of wild-type strain in
      response to Avicel and demonstrated that Stp1 somehow repressed induction of the
      bulk of major cellulase and hemicellulose genes. Two other putative major
      facilitator superfamily sugar transporters were, however, up-regulated in the
      profiling. Deletion of one of them identified Crt1 that was required for growth
      and enzymatic activity on cellulose or lactose, but was not required for growth
      or hemicellulase activity on xylan. The essential role of Crt1 in cellulase
      induction did not seem to rely on its transporting activity because the overall
      uptake of cellobiose or sophorose by T. reesei was not compromised in the absence
      of Crt1. Phylogenetic analysis revealed that orthologs of Crt1 exist in the
      genomes of many filamentous ascomycete fungi capable of degrading cellulose.
      These data thus shed new light on the mechanism by which T. reesei senses and
      transmits the cellulose signal and offers potential strategies for strain
      improvement. 

PMID- 24085298
TI  - miR-29 promotes murine osteoclastogenesis by regulating osteoclast commitment and
      migration.
AB  - Osteoclast differentiation is regulated by transcriptional, post-transcriptional,
      and post-translational mechanisms. MicroRNAs are fundamental post-transcriptional
      regulators of gene expression. The function of the miR-29 (a/b/c) family in cells
      of the osteoclast lineage is not well understood. In primary cultures of mouse
      bone marrow-derived macrophages, inhibition of miR-29a, -29b, or -29c diminished
      formation of TRAP (tartrate-resistant acid phosphatase-positive) multinucleated
      osteoclasts, and the osteoclasts were smaller. Quantitative RT-PCR showed that
      all miR-29 family members increased during osteoclast differentiation, in concert
      with mRNAs for the osteoclast markers Trap (Acp5) and cathepsin K. Similar
      regulation was observed in the monocytic cell line RAW264.7. In stably transduced
      RAW264.7 cell lines expressing an inducible miR-29 competitive inhibitor (sponge
      construct), miR-29 knockdown impaired osteoclastic commitment and migration of
      pre-osteoclasts. However, miR-29 knockdown did not affect cell viability, actin
      ring formation, or apoptosis in mature osteoclasts. To better understand how miR
      29 regulates osteoclast function, we validated miR-29 target genes using
      Luciferase 3'-UTR reporter assays and specific miR-29 inhibitors. We demonstrated
      that miR-29 negatively regulates RNAs critical for cytoskeletal organization,
      including Cdc42 (cell division control protein 42) and Srgap2 (SLIT-ROBO Rho
      GTPase-activating protein 2). Moreover, miR-29 targets RNAs associated with the
      macrophage lineage: Gpr85 (G protein-coupled receptor 85), Nfia (nuclear factor
      I/A), and Cd93. In addition, Calcr (calcitonin receptor), which regulates
      osteoclast survival and resorption, is a novel miR-29 target. Thus, miR-29 is a
      positive regulator of osteoclast formation and targets RNAs important for
      cytoskeletal organization, commitment, and osteoclast function. We hypothesize
      that miR-29 controls the tempo and amplitude of osteoclast differentiation. 

PMID- 24085299
TI  - Vaccine-derived mutation in motif D of poliovirus RNA-dependent RNA polymerase
      lowers nucleotide incorporation fidelity.
AB  - All viral RNA-dependent RNA polymerases (RdRps) have a conserved structural
      element termed motif D. Studies of the RdRp from poliovirus (PV) have shown that
      a conformational change of motif D leads to efficient and faithful nucleotide
      addition by bringing Lys-359 into the active site where it serves as a general
      acid. The RdRp of the Sabin I vaccine strain has Thr-362 changed to Ile. Such a
      drastic change so close to Lys-359 might alter RdRp function and contribute in
      some way to the attenuated phenotype of Sabin type I. Here we present our
      characterization of the T362I RdRp. We find that the T362I RdRp exhibits a
      mutator phenotype in biochemical experiments in vitro. Using NMR, we show that
      this change in nucleotide incorporation fidelity correlates with a change in the
      structural dynamics of motif D. A recombinant PV expressing the T362I RdRp
      exhibits normal growth properties in cell culture but expresses a mutator
      phenotype in cells. For example, the T362I-containing PV is more sensitive to the
      mutagenic activity of ribavirin than wild-type PV. Interestingly, the T362I
      change was sufficient to cause a statistically significant reduction in viral
      virulence. Collectively, these studies suggest that residues of motif D can be
      targeted when changes in nucleotide incorporation fidelity are desired. Given the
      observation that fidelity mutants can serve as vaccine candidates, it may be
      possible to use engineering of motif D for this purpose. 

PMID- 24085300
TI  - Structural basis for the different stability and activity between the Cdk5
      complexes with p35 and p39 activators.
AB  - Cyclin-dependent kinase 5 (Cdk5) is a brain-specific membrane-bound protein
      kinase that is activated by binding to the p35 or p39 activator. Previous studies
      have focused on p35-Cdk5, and little is known regarding p39-Cdk5. The lack of
      functional understanding of p39-Cdk5 is due, in part, to the labile property of
      p39-Cdk5, which dissociates and loses kinase activity in nonionic detergent
      conditions. Here we investigated the structural basis for the instability of p39
      Cdk5. p39 and p35 contain N-terminal p10 regions and C-terminal Cdk5 activation
      domains (AD). Although p35 and p39 show higher homology in the C-terminal AD than
      the N-terminal region, the difference in stability is derived from the C-terminal
      AD. Based on the crystal structures of the p25 (p35 C-terminal region including
      AD)-Cdk5 complex, we simulated the three-dimensional structure of the p39 AD-Cdk5
      complex and found differences in the hydrogen bond network between Cdk5 and its
      activators. Three amino acids of p35, Asp-259, Asn-266, and Ser-270, which are
      involved in hydrogen bond formation with Cdk5, are changed to Gln, Gln, and Pro
      in p39. Because these three amino acids in p39 do not participate in hydrogen
      bond formation, we predicted that the number of hydrogen bonds between p39 and
      Cdk5 was reduced compared with p35 and Cdk5. Using substitution mutants, we
      experimentally validated that the difference in the hydrogen bond network
      contributes to the different properties between Cdk5 and its activators. 

PMID- 24085301
TI  - Substrate binding promotes formation of the Skp1-Cul1-Fbxl3 (SCF(Fbxl3)) protein
      complex.
AB  - The Skp1-Cul1-F-box protein (SCF) complex is one of the most well characterized
      types of ubiquitin ligase (E3), with the E3 activity of the complex being
      regulated in part at the level of complex formation. Fbxl3 is an F-box protein
      that is responsible for the ubiquitylation and consequent degradation of
      cryptochromes (Crys) and thus regulates oscillation of the circadian clock. Here
      we show that formation of the SCF(Fbxl3) complex is regulated by substrate
      binding in vivo. Fbxl3 did not associate with Skp1 and Cul1 to a substantial
      extent in transfected mammalian cells. Unexpectedly, however, formation of the
      SCF(Fbxl3) complex was markedly promoted by forced expression of its substrate
      Cry1 in these cells. A mutant form of Fbxl3 that does not bind to Cry1 was unable
      to form an SCF complex, suggesting that interaction of Cry1 with Fbxl3 is
      essential for formation of SCF(Fbxl3). In contrast, recombinant Fbxl3 associated
      with recombinant Skp1 and Cul1 in vitro even in the absence of recombinant Cry1.
      Domain-swap analysis revealed that the COOH-terminal leucine-rich repeat domain
      of Fbxl3 attenuates the interaction of Skp1, suggesting that a yet unknown
      protein associated with the COOH-terminal domain of Fbxl3 and inhibited SCF
      complex formation. Our results thus provide important insight into the regulation
      of both SCF ubiquitin ligase activity and circadian rhythmicity. 

PMID- 24085302
TI  - Menadione (vitamin K3) is a catabolic product of oral phylloquinone (vitamin K1)
      in the intestine and a circulating precursor of tissue menaquinone-4 (vitamin K2)
      in rats.
AB  - Mice have the ability to convert dietary phylloquinone (vitamin K1) into
      menaquinone-4 (vitamin K2) and store the latter in tissues. A prenyltransferase
      enzyme, UbiA prenyltransferase domain-containing 1 (UBIAD1), is involved in this
      conversion. There is evidence that UBIAD1 has a weak side chain cleavage activity
      for phylloquinone but a strong prenylation activity for menadione (vitamin K3),
      which has long been postulated as an intermediate in this conversion. Further
      evidence indicates that when intravenously administered in mice phylloquinone can
      enter into tissues but is not converted further to menaquinone-4. These findings
      raise the question whether phylloquinone is absorbed and delivered to tissues in
      its original form and converted to menaquinone-4 or whether it is converted to
      menadione in the intestine followed by delivery of menadione to tissues and
      subsequent conversion to menaquinone-4. To answer this question, we conducted
      cannulation experiments using stable isotope tracer technology in rats. We
      confirmed that the second pathway is correct on the basis of structural
      assignments and measurements of phylloquinone-derived menadione using high
      resolution MS analysis and a bioassay using recombinant UBIAD1 protein.
      Furthermore, high resolution MS and (1)H NMR analyses of the product generated
      from the incubation of menadione with recombinant UBIAD1 revealed that the
      hydroquinone, but not the quinone form of menadione, was an intermediate of the
      conversion. Taken together, these results provide unequivocal evidence that
      menadione is a catabolic product of oral phylloquinone and a major source of
      tissue menaquinone-4. 

PMID- 24085303
TI  - Loop motions important to product expulsion in the Thermobifida fusca glycoside
      hydrolase family 6 cellobiohydrolase from structural and computational studies.
AB  - Cellobiohydrolases (CBHs) are typically major components of natural enzyme
      cocktails for biomass degradation. Their active sites are enclosed in a tunnel,
      enabling processive hydrolysis of cellulose chains. Glycoside hydrolase Family 6
      (GH6) CBHs act from nonreducing ends by an inverting mechanism and are present in
      many cellulolytic fungi and bacteria. The bacterial Thermobifida fusca Cel6B
      (TfuCel6B) exhibits a longer and more enclosed active site tunnel than its fungal
      counterparts. Here, we determine the structures of two TfuCel6B mutants co
      crystallized with cellobiose, D274A (catalytic acid), and the double mutant
      D226A/S232A, which targets the putative catalytic base and a conserved serine
      that binds the nucleophilic water. The ligand binding and the structure of the
      active site are retained when compared with the wild type structure, supporting
      the hypothesis that these residues are directly involved in catalysis. One
      structure exhibits crystallographic waters that enable construction of a model of
      the alpha-anomer product after hydrolysis. Interestingly, the product sites of
      TfuCel6B are completely enclosed by an "exit loop" not present in fungal GH6 CBHs
      and by an extended "bottom loop". From the structures, we hypothesize that either
      of the loops enclosing the product subsites in the TfuCel6B active site tunnel
      must open substantially for product release. With simulation, we demonstrate that
      both loops can readily open to allow product release with equal probability in
      solution or when the enzyme is engaged on cellulose. Overall, this study reveals
      new structural details of GH6 CBHs likely important for functional differences
      among enzymes from this important family. 

PMID- 24085304
TI  - Elongation factor-1alpha is a novel protein associated with host cell invasion
      and a potential protective antigen of Cryptosporidium parvum.
AB  - The phylum Apicomplexa comprises obligate intracellular parasites that infect
      vertebrates. All invasive forms of Apicomplexa possess an apical complex, a
      unique assembly of organelles localized to the anterior end of the cell and
      involved in host cell invasion. Previously, we generated a chicken monoclonal
      antibody (mAb), 6D-12-G10, with specificity for an antigen located in the apical
      cytoskeleton of Eimeria acervulina sporozoites. This antigen was highly conserved
      among Apicomplexan parasites, including other Eimeria spp., Toxoplasma, Neospora,
      and Cryptosporidium. In the present study, we identified the apical cytoskeletal
      antigen of Cryptosporidium parvum (C. parvum) and further characterized this
      antigen in C. parvum to assess its potential as a target molecule against
      cryptosporidiosis. Indirect immunofluorescence demonstrated that the reactivity
      of 6D-12-G10 with C. parvum sporozoites was similar to those of anti-beta- and
      anti-gamma-tubulins antibodies. Immunoelectron microscopy with the 6D-12-G10 mAb
      detected the antigen both on the sporozoite surface and underneath the inner
      membrane at the apical region of zoites. The 6D-12-G10 mAb significantly
      inhibited in vitro host cell invasion by C. parvum. MALDI-TOF/MS and LC-MS/MS
      analysis of tryptic peptides revealed that the mAb 6D-12-G10 target antigen was
      elongation factor-1alpha (EF-1alpha). These results indicate that C. parvum EF
      1alpha plays an essential role in mediating host cell entry by the parasite and,
      as such, could be a candidate vaccine antigen against cryptosporidiosis. 

PMID- 24085306
TI  - Physiological and anthropometric progression in an international oarsman: a 15
      year case study.
AB  - PURPOSE: In this case study, a world-class rower was followed over a period of 15
      y in which he evolved from junior to professional athlete. METHODS: An
      incremental exercise test and a 2000-m ergometer test were performed each year in
      the peak period of the season starting at the age of 16 y. In addition, the
      training logs of 1 y each as a junior and a senior rower were recorded and
      analyzed. RESULTS: Maximal oxygen uptake (VO(2max)), maximal power output
      (P(max)), and power output at 4 mmol/L blood lactate concentration increased
      until the age of 27 and then stabilized at 30 y at 6.0 +/- 0.2 L/min, 536 +/- 15
      W, and 404 +/- 22 W, respectively. At the age of 27-28 y the rower also had a
      career-best 2000-m ergometer test (5'58") and on-water performance with a 4th
      place at the Olympic Games (2008) in Beijing and World Championships (2009). At
      the age of 23 y, the rower trained a total of 6091 km in 48 wk. Of the total
      training time, 15.4% consisted of general training practices, 23.4% resistance
      training, and 61.2% specific rowing training. CONCLUSION: The on-water
      performance in the World Championships and Olympic Games corresponded closely to
      the evolution in the rower's physiological profile and 2000-m ergometer
      performance. The long-term build-up program resulted in an increase in the
      physiological parameters up to the age of 27 y and resulted in a 4th position at
      the 2008 Olympic Games at a body mass of only 86 kg.

PMID- 24085305
TI  - Glycosylation in a mammalian expression system is critical for the production of
      functionally active leukocyte immunoglobulin-like receptor A3 protein.
AB  - The leukocyte immunoglobulin-like receptor (LILR) A3 is a member of the highly
      homologous activating and inhibitory receptors expressed on leukocytes. LILRA3 is
      a soluble receptor of unknown functions but is predicted to act as a broad
      antagonist to other membrane-bound LILRs. Functions of LILRA3 are unclear
      primarily because of the lack of high quality functional recombinant protein and
      insufficient knowledge regarding its ligand(s). Here, we expressed and
      characterized recombinant LILRA3 (rLILRA3) proteins produced in 293T cells,
      Escherichia coli, and Pichia pastoris. We found that the purified rLILRA3
      produced in the mammalian system was the same size as a 70-kDa native macrophage
      LILRA3. This is 20 kDa larger than the calculated size, suggesting significant
      post-translational modifications. In contrast, rLILRA3 produced in E. coli was
      similar in size to the unprocessed protein, but yeast-produced protein was 2-4
      times larger than the unprocessed protein. Treatment with peptide-N-glycosidase F
      reduced the size of the mammalian cell- and yeast-produced rLILRA3 to 50 kDa,
      suggesting that most modifications are due to glycosylation. Consistent with
      this, mass spectrometric analysis of the mammalian rLILRA3 revealed canonical N
      glycosylation at the predicted Asn(140), Asn(281), Asn(302), Asn(341), and
      Asn(431) sites. Functionally, only mammalian cell-expressed rLILRA3 bound onto
      the surface of monocytes with high affinity, and importantly, only this
      significantly abrogated LPS-induced TNFalpha production by monocytes. Binding to
      monocytes was partially blocked by beta-lactose, indicating that optimally
      glycosylated LILRA3 might be critical for ligand binding and function. Overall,
      our data demonstrated for the first time that LILRA3 is a potential new anti
      inflammatory protein, and optimal glycosylation is required for its functions. 

PMID- 24085307
TI  - Organ- and stress-specific expression of the ASR genes in rice.
AB  - KEY MESSAGE: Rice ASR genes respond distinctly to abscisic acid, dehydration and
      cold stress. Their tissue-specific expression provides new hints about their
      possible roles in plant responses to stress. Plant ASR proteins have emerged as
      an interesting distinct group of proteins with apparent roles in protecting
      cellular structures as well as putative regulators of gene expression, both
      important responses of plants to environmental stresses. Regardless of the
      possible functions proposed by different studies, little is known about their
      role in cereals. To further understand the function of these proteins in the
      Gramineae, we investigated the expression pattern of the six ASR genes present in
      the rice genome in response to ABA, stress conditions and in different organs.
      Although transcription of most OsASRs is transiently enhanced by ABA treatment,
      the genes present a differential response under cold and drought stress as well
      as specific expression in certain tissues and organs. Analysis of their promoters
      reveals regulatory cis-elements associated to hormonal, sugar and stress
      responses. The promoters of two genes, OsASR1 and OsASR5, direct the expression
      of the GUS reporter gene especially to leaf vascular tissue in response to
      dehydration and low temperature. In control conditions, a GUS reporter assay also
      indicates specific expression of these two genes in roots, anthers and seed
      scutellar tissues. These results provide new clues about the possible role of
      ASRs in plant stress responses and development.

PMID- 24085308
TI  - RNAi-mediated suppression of endogenous storage proteins leads to a change in
      localization of overexpressed cholera toxin B-subunit and the allergen protein
      RAG2 in rice seeds.
AB  - KEY MESSAGE: RNAi-mediated suppression of the endogenous storage proteins in
      MucoRice-CTB-RNAi seeds affects not only the levels of overexpressed CTB and RAG2
      allergen, but also the localization of CTB and RAG2. A purification-free rice
      based oral cholera vaccine (MucoRice-CTB) was previously developed by our
      laboratories using a cholera toxin B-subunit (CTB) overexpression system.
      Recently, an advanced version of MucoRice-CTB was developed (MucoRice-CTB-RNAi)
      through the use of RNAi to suppress the production of the endogenous storage
      proteins 13-kDa prolamin and glutelin, so as to increase CTB expression. The
      level of the alpha-amylase/trypsin inhibitor-like protein RAG2 (a major rice
      allergen) was reduced in MucoRice-CTB-RNAi seeds in comparison with wild-type
      (WT) rice. To investigate whether RNAi-mediated suppression of storage proteins
      affects the localization of overexpressed CTB and major rice allergens, we
      generated an RNAi line without CTB (MucoRice-RNAi) and investigated gene
      expression, and protein production and localization of two storage proteins, CTB,
      and five major allergens in MucoRice-CTB, MucoRice-CTB-RNAi, MucoRice-RNAi, and
      WT rice. In all lines, glyoxalase I was detected in the cytoplasm, and 52- and 63
      kDa globulin-like proteins were found in the aleurone particles. In WT, RAG2 and
      19-kDa globulin were localized mainly in protein bodies II (PB-II) of the
      endosperm cells. Knockdown of glutelin A led to a partial destruction of PB-II
      and was accompanied by RAG2 relocation to the plasma membrane/cell wall and
      cytoplasm. In MucoRice-CTB, CTB was localized in the cytoplasm and PB-II. In
      MucoRice-CTB-RNAi, CTB was produced at a level six times that in MucoRice-CTB and
      was localized, similar to RAG2, in the plasma membrane/cell wall and cytoplasm.
      Our findings indicate that the relocation of CTB in MucoRice-CTB-RNAi may
      contribute to down-regulation of RAG2.

PMID- 24085310
TI  - Unexpected optical activity of cerium in Y2O3:Ce3+, Yb3+, Er3+ up and down
      conversion system.
AB  - In this work we synthesized rare earth-doped yttria nanocrystals via the Pechini
      method. We used Ce(3+), Yb(3+) and Er(3+) as dopant ions and studied their
      behavior when they are simultaneously embedded in the yttrium oxide lattice. The
      tri-doped system exhibits both downshifting and up-converting properties, due to
      the presence of, respectively, cerium-erbium and ytterbium-erbium couples.
      Efforts were put into determination of the effects of the presence of increasing
      content of cerium. We synthesized a series of samples having the general formula
      (Y0.88-xCexYb0.1Er0.02)2O3, where x = 0.01, 0.02, 0.10, 0.20, and 0.40. The
      structural properties of the samples were analyzed by the X-ray powder
      diffraction (XRPD) technique and the morphological features were disclosed using
      transmission electron microscope (TEM) observations. Photoluminescence properties
      were tested by carrying out photoluminescence (PL) emission, photoluminescence
      excitation (PLE) and lifetime (LT) measurements. 

PMID- 24085309
TI  - Optimizing the transient Fast Agro-mediated Seedling Transformation (FAST) method
      in Catharanthus roseus seedlings.
AB  - KEY MESSAGE: An Agro-mediated transformation method has been adapted in
      Catharanthus roseus seedlings for transient overexpression. Our results suggest
      that Agro-mediated methods may induce defense-related genes, which should be
      considered in its application. The Fast Agro-mediated Seedling Transformation
      (FAST) method, which involves the co-cultivation and transient transformation of
      young seedlings with Agrobacterium, was adapted and optimized in Catharanthus
      roseus. We investigated the optimal conditions for Gus expression by varying the
      Agrobacterium density (OD600 = 0.29 and 0.50), A. rhizogenes strain (15834 and
      R1000), and co-cultivation time in liquid (2, 12, or 24 h) followed by incubation
      time on solid media (1 or 2 days). Transformation efficiency was assessed
      quantitatively in terms of average GUS intensity per cotyledon surface area and
      percentage of cotyledons transformed. GUS staining was observed in 100% of
      cotyledons co-cultivated with A. rhizogenes (OD600 = 0.50) co-transformed with
      the Mas promoter-driven Gus and pSoup helper plasmids, in the presence of 0.01%
      v/v Silwet L-77 for 24 h in liquid followed by 2-days on solid media. In
      addition, we observed that co-cultivation with Agrobacterium strongly induced
      Zct1 and Orca3, two transcription factors known to regulate defense-related
      alkaloid biosynthesis in C. roseus. Homologous transcription factors regulate
      defense responses in many plant species. Therefore, possible induction of defense
      related genes by Agro-mediated transformation should be a consideration in
      experimental design.

PMID- 24085311
TI  - The influence of race on end-of-life choices following a counselor-based
      palliative consultation.
AB  - Black Americans are more likely than whites to choose aggressive medical care at
      the end of life. We present a retrospective cohort study of 2843 patients who
      received a counselor-based palliative care consultation at a large US
      southeastern hospital. Before the palliative consultation, 72.8% of the patients
      had no restrictions in care, and only 4.6% had chosen care and comfort only
      (CCO). After the consult, these choices dramatically changed, with only 17.5%
      remaining full code and 43.3% choosing CCO. Both before and after palliative
      consultation, blacks chose more aggressive medical care than whites, but racial
      differences diminished after the counselor-based consultation. Both African
      American and white patients and families receiving a counselor-based palliative
      consultation in the hospital make profound changes in their preferences for life
      sustaining treatments. 

PMID- 24085312
TI  - Noncomfort medication use in acute care inpatients comanaged by palliative care
      specialists near the end of life: a cohort study.
AB  - BACKGROUND/OBJECTIVE: To examine comfort medication (CM) and noncomfort (NC)
      medication use in inpatients comanaged by palliative care (PC) near the end of
      life. METHODS: Chart review of inpatients comanaged by the PC service at 2
      academic hospitals. Medications were categorized as CM and NC medication
      according to the published guidelines. RESULTS: Seventy patients met inclusion
      criteria. In the final week of life, inpatients were receiving a mean of 6 CM (40
      doses) and 7 NC medications (41 doses). Four new NC medications were started per
      patient, but only 3 were discontinued. The NC medications were most frequently
      discontinued on the day of PC consult, but 14% were stopped on the day of
      death/PC unit transfer. CONCLUSION: Inpatients comanaged by PC continue to
      receive NC medications as they near the end of life.

PMID- 24085313
TI  - Management of acute basilar artery occlusion: should any treatment strategy
      prevail?
AB  - BACKGROUND: Acute basilar artery occlusion (BAO) is relatively infrequent form of
      acute ischemic stroke associated with severe and persisting neurological deficit
      and high mortality rate (to 86%). Early recanalization is essential for good
      clinical outcome but the most effective treatment approach remains unestablished.
      Several treatment strategies are currently available but their safety and
      efficacy have only been tested in retrospective/prospective case series.
      Randomized controlled trials (RCTs) are lacking. METHODS AND RESULTS: We searched
      the PubMed database for assessments of recanalization rate and clinical outcome
      in BAO patients treated with various treatment methods. The results show that
      antithrombotics are least effective while specific reperfusion therapies
      including intravenous thrombolysis (IVT) and various types of intra-arterial
      therapy (IAT) are more so. Less than half of BAO patients reach independent
      outcome following IVT with a recanalization rate 52-78%. Even though IAT
      recanalizes BAO more frequently (in up to 100%), the higher recanalization rate
      is not necessarily associated with better outcome. CONCLUSIONS: Good clinical
      outcome is strongly dependent on recanalization time. Thus, the concept of
      bridging therapy, combining widely available IVT with IAT, was introduced and is
      usually considered a rescue strategy in non-responders to IV alteplase. A trend
      to better outcome in patients treated with bridging therapy in some studies, has
      to be confirmed by large RCTs.

PMID- 24085314
TI  - Metabolic disorders due to methanol poisoning.
AB  - AIM: The aim of this study is to compare markers of glomerular filtration rate
      (GFR), estimated GFR (eGFR), and metabolic parameters between admission and
      recovery in 13 patients of Tomas Bata hospital with methanol poisoning during
      methanol problems in the Czech Republic in 2012. The impact of methanol
      concentration and age on metabolic parameters were discovered at the time of
      admission to hospital. MATERIALS AND METHODS: The serum osmolality, methanol,
      ethanol, creatinine, cystatin C, Troponin I, ALT, plasma pH and lactate were
      measured in these 13 patients. The eGFR from serum creatinine (creatnine eGFR)
      and from cystatin C (cystatin C eGFR) were also determined. RESULTS: Increased
      serum osmolality and markers of metabolic acidosis are key indirect laboratory
      findings in patients with methanol poisoning. There were no significant changes
      in eGFR in our patients between admission and recovery. Increased serum troponin
      I concentration was confirmed as an indicator of myocardial necrosis in four
      patients. Two patients developed acute kidney injury (AKI) before admission.
      CONCLUSIONS: We found statistically significant differences in serum osmolality
      concentration, plasma pH and lactate between admission and recovery. We found no
      changes in eGFR between admission and recovery. One patient had vision problems
      due to damage to the occipital lobes. Methanol poisoning may cause increase in
      markers of cardiac damage.

PMID- 24085315
TI  - Nucleus Accumbens stereotaxy for deep brain stimulation: anatomical focus.

PMID- 24085316
TI  - The silent phase of diffuse low-grade gliomas. Is it when we missed the action?
AB  - BACKGROUND: It is commonly believed that, before being diagnosed after onset of
      symptoms, diffuse low-grade glioma evolve silently for a long time. The present
      study aimed to estimate for the first time the exact duration of this silent
      phase, during which the glioma is radiologically visible but undiscovered.
      METHODS: We retrospectively reviewed our French national database of diffuse low
      grade glioma, searching for patients with an MRI-based assessment of their
      velocity of diameter growth at diagnosis and before any treatment (at least three
      MRIs over more than 6 months). For each patient, the duration of the silent phase
      was estimated by the formula: duration = initial diameter / initial velocity of
      growth. RESULTS: A total of 148 patients were included in the study. The mean
      lead-time duration (i.e., duration of the silent phase) was 14.0 +/- 7.8 years
      (median, 11.6 ; range, 1.6-39.4). The lead-time is statistically not correlated
      to the tumor volume. It is markedly decreasing with the velocity of diameter
      expansion. CONCLUSIONS: Diffuse low-grade glioma are radiologically detectable
      but clinically silent for more than a decade. Such a long period of silent
      evolution could explain our current failure to cure these tumors. It can also be
      viewed as a window of opportunity to detect these tumors earlier, suggesting the
      need to set up a screening program.

PMID- 24085317
TI  - Dehydration induced 2D-to-3D crystal-to-crystal network re-assembly and
      ferromagnetism tuning within two chiral copper(II)-tartrate coordination
      polymers.
AB  - The synthesis of two homochiral l-tartrate-copper(II) coordination polymers,
      [Cu2(C4H4O6)2(H2O)2.xH2O]n (1), and [Cu(C4H4O6)]n (2), under hydrothermal
      conditions, is reported. Compound 1 adopts a 2D layered network structure with a
      space group of P21, while compound 2 features a 3D network structure with a space
      group P21212. Interestingly, the 2D layered structure of compound 1 can undergo a
      crystal-to-crystal network reassembly, with the formation of the 3D network
      structure of compound 2 under dehydration conditions. Variable temperature and
      field magnetic studies reveal the existence of a distinct ferromagnetic
      interaction between Cu(2+) ions as the result of distinct syn-anti carboxylate
      bridging coordination modes.

PMID- 24085318
TI  - Effects of four antitussives on airway neurogenic inflammation in a guinea pig
      model of chronic cough induced by cigarette smoke exposure.
AB  - OBJECTIVE: The effects of four antitussives, including codeine phosphate (CP),
      moguisteine, levodropropizine (LVDP) and naringin, on airway neurogenic
      inflammation and enhanced cough were investigated in guinea pig model of chronic
      cough. METHODS: Guinea pigs were exposed to CS for 8 weeks. At the 7th and 8th
      week, the animals were treated with vehicle, CP (4.8 mg/kg), moguisteine (24
      mg/kg), LVDP (14 mg/kg) and naringin (18.4 mg/kg) respectively. Then the cough
      and the time-enhanced pause area under the curve (Penh-AUC) during capsaicin
      challenge were recorded. The substance P (SP) content, NK-1 receptor expression
      and neutral endopeptidase (NEP) activity in lung were determined. RESULTS:
      Chronic CS exposure induced a bi-phase time course of cough responsiveness to
      capsaicin. Eight weeks of CS exposure significantly enhanced the airway
      neurogenic inflammation and cough response in guinea pigs. Two weeks of treatment
      with CP, moguisteine, LVDP or naringin effectively attenuated the chronic CS
      exposure enhanced cough. Only naringin exerted significant effect on inhibiting
      Penh-AUC, SP content and NK-1 receptor expression, as well as preventing the
      declining of NEP activity in lung. CONCLUSIONS: Chronic CS-exposed guinea pig is
      suitable for studying chronic pathological cough, in which naringin is effective
      on inhibiting both airway neurogenic inflammation and enhanced cough.

PMID- 24085319
TI  - Combining clinical and analytical parameters improves prediction of malignant
      pleural effusion.
AB  - PURPOSE: The usefulness of a panel of tumour markers and clinical-radiological
      criteria for diagnosing malignant pleural effusion (MPE) is not clearly stated.
      Our purpose was to assess the performance of those parameters in the diagnosis of
      MPE. METHODS: Consecutive patients with exudative PE were enrolled and divided
      into two groups: MPE and non-MPE. Logistic regression analysis was used to
      estimate the probability of MPE. Four prognostic models were considered: (1)
      clinical-radiological variables; (2) analytical variables; (3) combination of
      clinical and analytical variables; and (4) simpler model removing some analytical
      variables. Calibration and discrimination (receiver operating characteristics
      curves and AUC) were performed. RESULTS: A total of 491 pleural exudates were
      included: tuberculous (n = 72), malignant (n = 211), parapneumonic (n = 115),
      empyemas (n = 32), or miscellaneous (n = 61). The AUC obtained with Model 1
      (absence of chest pain and fever and radiological images compatible with
      malignancy), Model 2 (CEA, NSE, CYFRA 21-1, and TPS), Model 3 (sum of the
      variables of models 1 and 2), and Model 4 (the variables of model 1 plus CEA)
      were 0.918, 0.832, 0.952 (all with a P < 0.05), and 0.939 (P < 0.01 compared to
      models 1 and 2), respectively. The correct classification rate for Models 1, 2,
      3, and 4, was 87.2, 79.5, 88.4, and 87.6 %, respectively. CONCLUSIONS: All models
      analysed had a good diagnostic yield for MPE, being greater in those that
      combined radiological and analytical criteria. Although Model 3 obtained a higher
      yield, the simplest model (Model 4) is very attractive due to its simplicity of
      use in daily practice.

PMID- 24085320
TI  - Relationship between quantitative CT metrics and pulmonary function in combined
      pulmonary fibrosis and emphysema.
AB  - PURPOSE: Combined pulmonary fibrosis and emphysema (CPFE) is increasingly
      recognized, as current reports of its clinical features show. To determine CPFE's
      physiologic and radiologic features, we conducted quantitative assessment of
      computed tomography scans to compare with those of chronic obstructive pulmonary
      disease (COPD). METHODS: In 23 patients with CPFE and 42 patients with COPD, we
      measured the extent of emphysema (LAA %), parenchymal density, and total cross
      sectional areas of pulmonary vessels smaller than 5 mm(2) (%CSA <5) and 5-10
      mm(2) (%CSA 5-10). RESULTS: For CPFE, airflow was better, but diffusing capacity
      for carbon monoxide (DLCO) was worse than for COPD, whereas LAA % was similar for
      both groups. The %CSA <5 was greater but %CSA5-10 was less in CPFE than COPD.
      COPD involved a negative correlation between DLCO and LAA % at all lung sites;
      those factors correlated for CPFE only in the upper lobe (r = -0.535). In
      contrast, CPFE had a negative correlation between DLCO and parenchymal density in
      lower lobes (r = -0.453), but COPD showed no correlation in any such sections. In
      CPFE, no correlation was apparent between LAA in upper lobes and parenchymal
      density in lower lobes. The annual rate of FVC decline (-169.26 ml/year) in CPFE
      patients correlated with parenchymal density (r = -0.714). CONCLUSIONS: In CPFE,
      fibrosis and emphysema apparently existed independently, but both correlate with
      and likely contribute to the disproportionate reduction in gas exchange. Our
      study also suggested that pulmonary fibrotic changes may be more important
      contributors than emphysema for disease progression.

PMID- 24085321
TI  - An unusual foreign body after dental filling.
AB  - We report a case of a 71-year-old Caucasian woman who was referred to our
      emergency department for acute onset of dyspnoea and dry cough. She underwent
      dental filling for caries ~2 h before. During the treatment, the distal part of
      the odontoiatric drill unintentionally fell off into the patient's oral cavity
      and was accidentally inhaled. Posteroanterior chest X-ray evidenced the foreign
      body localized in the right bronchial tree. A chest computed tomography scan
      showed the drill (with the tip pointed upward) wedged at the beginning of the
      right basal pyramid. A subsequent fiberoptic bronchoscopy confirmed the tip of
      the drill in the right lower bronchus, and the foreign body was easily removed
      due to the favorable position of the tip. The patient was discharged in first
      postoperative day without consequences. 

PMID- 24085322
TI  - Artemisinin rewires the protein interaction network in cancer cells: network
      analysis, pathway identification, and target prediction.
AB  - Artemisinin and related compounds (artemisinins), as a frontline treatment for
      malaria, have been used to save millions of lives. Their potential application in
      cancer treatment is promising. Nevertheless, the precise mechanisms of action of
      artemisinins are still controversial. In particular, the system-level influence
      of artemisinins on protein interactions and regulatory networks remains unknown,
      limiting progress in development of this class of compounds as anticancer drugs.
      In the present study, we investigated the mechanism of action of artemisinins in
      cancer therapy through an analysis based on biological networks. According to
      experimental evidence from more than 400 literature studies, 558 key proteins
      were derived and the artemisinins-rewired protein interaction network was
      constructed. Topological properties were analyzed to show that the protein
      network was a scale-free biological system. And the modularity analysis and
      pathway identification were performed. Five key pathways including PI3K-Akt, T
      cell receptor, Toll-like receptor, TGF-beta and insulin signaling pathways were
      involved in artemisinins-mediated anticancer effects; their identification was
      confirmed by microarray data. Based on these results, predictions were made about
      the targets of artemisinins in various pathways. These results provide a deeper
      understanding of the molecular mechanisms of action of artemisinins and will
      contribute to the development and application of this class of compounds in
      cancer treatment. 

PMID- 24085323
TI  - In vitro modulation of MMP-2 and MMP-9 in adult human sarcoma cell lines by
      cytokines, inducers and inhibitors.
AB  - The highly aggressive adult sarcomas are characterized by high levels of matrix
      metalloproteinase (MMP)-2 and -9, which play crucial roles in tumor invasion and
      metastasis by degradation of the extracellular membrane leading to cancer cell
      spread to distal organs. We examined the effect of cytokines, mitogens, inducers
      and inhibitors on MMP-2 and MMP-9 secretion in chondrosarcoma (SW-1353),
      fibrosarcoma (HT-1080), liposarcoma (SW-872) and synovial sarcoma (SW-982) cell
      lines. The selected compounds included natural cytokines and growth factors, as
      well as chemical compounds applied in therapy of sarcoma and natural compounds
      that have demonstrated anticancer therapeutic potential. MMP-2 and MMP-9
      secretions were analyzed by gelatinase zymography following 24-h exposure to the
      tested agents and quantitated by densitometry. Fibrosarcoma, chondrosarcoma,
      liposarcoma and synovial sarcoma showed bands corresponding to MMP-2 and MMP-9
      with dose-dependent enhancement of MMP-9 with phorbol 12-myristate 13-acetate
      (PMA) treatment. In chondrosarcoma cells, tumor necrosis factor (TNF)-alpha had a
      stimulatory effect on MMP-9 and insignificant effect on MMP-2 and interleukin
      (IL)-1beta stimulated MMP-9 and MMP-2. In fibrosarcoma and liposarcoma cells, TNF
      alpha had a profound stimulatory effect on MMP-9, but no effect on MMP-2 and in
      synovial sarcoma an inhibitory effect on MMP-2 and no effect on MMP-9. IL-1beta
      had a slight inhibitory effect on fibrosarcoma, liposarcoma and synovial sarcoma
      MMP-2 and MMP-9 except for MMP-9 in synovial sarcoma which showed slight
      stimulation. Lipopolysaccharide (LPS) stimulated expression of MMP-2 in
      fibrosarcoma and chondrosarcoma while inhibited it in liposarcoma. Doxycycline,
      epigallocatechin gallate and the nutrient mixture inhibited MMP-2 and MMP-9 in
      all cell lines. Actinomycin-D, cyclohexamide, retinoic acid, and dexamethasone
      inhibited MMP-2 and -9 in chondrosarcoma and fibrosarcoma cells. Our results show
      that cytokines, mitogens, inducers and inhibitors have an up or down regulatory
      effect on MMP-2 and MMP-9 expression in adult sarcoma cell lines, suggesting
      these agents may be effective strategies to treat these cancers. 

PMID- 24085325
TI  - The origin of the strong interfacial charge-transfer absorption in the surface
      complex between TiO2 and dicyanomethylene compounds.
AB  - Interfacial charge transfer transitions between organic and inorganic materials
      are expected to be a potential photoinduced charge separation mechanism for
      photoenergy conversions. Recently, we reported that the hybrid material formed
      from TiO2 nanoparticles and an organic electron acceptor, 7,7,8,8
      tetracyanoquinodimethane (TCNQ), shows strong interfacial charge transfer
      absorption in the visible region. In this work, we have theoretically studied the
      structure, and electronic and absorption properties in order to clarify the
      formation mechanism and the origin of the strong interfacial charge transfer
      absorption. Density functional theory (DFT) calculations employing an anatase
      Ti14O28H2(OH)2(H2O)2 nano-cluster unraveled that the surface complex is formed by
      a nucleophilic addition reaction between a surface hydroxyl group of TiO2 and the
      carbon atom of the methylene moiety in TCNQ with the drastic changes in the
      structure and electronic properties of TCNQ. In the formation process, owing to
      the high electron affinity of TCNQ, a negative charge of the surface oxygen atom
      is transferred to the TCNQ moiety. This leads to a significant electronic
      hybridization between TiO2 and TCNQ, which is the origin of interfacial charge
      transfer transitions. 

PMID- 24085324
TI  - Comparison of intra-aortic computed tomography angiography to conventional
      angiography in the presurgical visualization of the Adamkiewicz artery: first
      results in patients with thoracoabdominal aortic aneurysms.
AB  - INTRODUCTION: The aim of this study was to compare the sensitivity of intra
      aortic computed tomography angiography (IA-CTA) to that of regular spinal digital
      subtraction angiography for the presurgical location of the Adamkiewicz artery
      (AKA). METHODS: Thirty patients (21 males, 9 females; mean age 64 years) had an
      IA-CTA for the location of the AKA before surgery of aneurysm (n = 24) or
      dissection (n = 6) of the thoracoabdominal aorta. After femoral artery puncture,
      a pigtail catheter was positioned at the origin of the descending aorta. CT
      acquisition was performed with an intra-aortic iodinated contrast media injection
      (15 mL/s, 120 mL). The visualization of the AKA and the location of the feeder(s)
      to the AKA were independently evaluated by two observers. Interrater agreement
      was calculated using a kappa test. Spinal angiogram by selective catheterization
      was systematically performed to confirm the results of the IA-CTA. RESULTS: The
      AKA was visualized by the IA-CTA in 27/30 cases (90 %); in 26/31 (84 %) cases,
      the continuity with the aorta was satisfactorily seen. Interrater agreement was
      good for the visualization of the AKA and its feeder(s): 0.625 and 0.87,
      respectively. In 75 % of the cases for which the AKA was visualized, the
      selective catheterization confirmed the results of the IA-CTA. In the remaining
      25 % of the cases, the selective catheterization could not be performed due to
      marked vessels' tortuosity or ostium stenosis. CONCLUSION: IA-CTA is a feasible
      technique in a daily practice that presents a good sensitivity for the location
      of the AKA.

PMID- 24085326
TI  - An anthropometric and physical profile of young Swiss alpine skiers between 2004
      and 2011.
AB  - PURPOSE: To describe the development of anthropometric and physical
      characteristics of young Swiss alpine skiers between 2004 and 2011, to compare
      them between age and performance-level groups, and to identify age- and sex
      dependent reference values for the tests performed. METHODS: The Swiss-Ski Power
      Test includes anthropometric measures and physical tests for coordination and
      speed, strength, anaerobic capacity, and endurance. The authors analyzed the
      results of 8176 tests performed by 1579 male and 1109 female alpine skiers
      between 2004 and 2011. Subjects ranged between regional and national level of
      performance and were grouped according to their competition age groups (U12, 11
      y; U14, 12-13 y; U16, 14-15 y; U18, 16-17 y; U21, 18-20 y) and performance level.
      RESULTS: A progressive increase in anthropometric measures and improvements in
      tests results with increasing age were found. For all tests, male athletes had
      better results than female athletes. Minor differences were observed in
      anthropometric characteristics between 2004 and 2011 (mostly <5%), while results
      of physical and coordinative tests showed significant improvements (up to more
      than 50% enhancement) or stability over the years. Differences between higher-
      and lower-level athletes were more pronounced in tests for lower-limb strength
      and anaerobic capacity. CONCLUSIONS: The presented profile of young Swiss alpine
      skiers highlights the improvements in different physical aspects along the
      maturation process and chronologically over a period of 7 y. Furthermore,
      reference values are provided for comparisons with alpine skiers or athletes from
      other sports.

PMID- 24085327
TI  - All-cause and disease-related health care costs associated with recurrent venous
      thromboembolism.
AB  - It was the objective of this study to quantify the risk of complications and the
      incremental health care costs associated with recurrent VTE events. Health care
      insurance claims from the Ingenix IMPACT database from 01/2004-09/2008 were
      analysed. Subjects aged >=18 years on the date of first recurrent VTE diagnosis
      with >=12 months of baseline observation prior to the index recurrent VTE were
      matched 1:1 with no-recurrent VTE patients based on propensity scores. The risk
      of developing post-thrombotic syndrome (PTS) and other disease-related diagnoses
      (thrombocytopenia, superficial venous thrombosis, venous ulcer, pulmonary
      hypertension, stasis dermatitis, and venous insufficiency) was compared between
      the recurrent and no-recurrent VTE groups for up to one year. All-cause and
      disease-related costs per patient per year (PPPY) were calculated. The recurrent
      VTE and no-recurrent VTE cohorts (8,001 subjects in each group) were matched with
      respect to age, gender, and comorbidities. The risk ratios (RRs) indicated that
      the risk of developing post-event complications was significantly higher for the
      recurrent VTE group compared to the no-recurrent VTE group (RR [95% CI]: PTS: 2.7
      [2.4 - 2.9], p-value <0.01). Patients with recurrent VTE had significantly higher
      average PPPY all-cause costs compared to no-recurrent VTE patients ($86,744
      versus $37,525, cost difference: $49,219 [?33,617]; 95% CI= 46,253-51,989).
      Corresponding disease-related health care costs PPPY were also significantly
      higher for the recurrent VTE group ($11,120 vs $1,262, cost difference: $9,858
      [?6,733]; 95% CI= $9,081-$10,476). In conclusion, in this large matched-cohort
      study, recurrent VTE patients had significantly higher risk of complications and
      health care costs compared to no-recurrent VTE patients. 

PMID- 24085328
TI  - Characterization of an isometric virus isolated from yam (Dioscorea rotundata) in
      Nigeria suggests that it belongs to a new species in the genus Aureusvirus.

PMID- 24085329
TI  - Impact of ileostomy-related complications on the multidisciplinary treatment of
      rectal cancer.
AB  - BACKGROUND: Radical resection is the primary treatment for rectal cancer. When
      anastomosis is possible, a temporary ileostomy is used to decrease morbidity from
      a poorly healed anastomosis. However, ileostomies are associated with
      complications, dehydration, and need for a second operation. We sought to
      evaluate the impact of ileostomy-related complications on the treatment of rectal
      cancer. METHODS: We conducted a retrospective study of patients who underwent
      sphincter-preserving surgery between January 2005 and December 2010 at a tertiary
      cancer center. The primary outcome was the overall rate of ileostomy-related
      complications. Secondary outcomes included complications related to ileostomy
      status, ileostomy closure, anastomotic complications at primary resection, rate
      of stoma closure, and completion of adjuvant chemotherapy assessed by
      multivariate logistic regression. RESULTS: Of 294 patients analyzed, 32% (n = 95)
      were women. Two hundred seventy-one (92%) received neoadjuvant chemoradiation.
      The median tumor distance from the anal verge was 7 cm (interquartile range 5-10
      cm). Two hundred eighty-one (96%) underwent stoma closure at a median of 7 months
      (interquartile range 5.4-8.3 months). The most common complication related to
      readmission was dehydration (n = 32-11%). Readmission within 60 days of primary
      resection was associated with delay in initiating adjuvant chemotherapy (odds
      ratio 3.01, 95% confidence interval 1.42-6.38, p = 0.004). CONCLUSIONS: Diverting
      ileostomies created during surgical treatment of rectal cancers are associated
      with morbidity; however, this is balanced against the risk of anastomosis-related
      morbidity at rectal resection. Given the potential benefit of fecal diversion,
      patient-oriented interventions to improve ostomy management, particularly during
      adjuvant chemotherapy, can be expected to yield marked benefits.

PMID- 24085330
TI  - In situ assembly of monodisperse, multifunctional silica microspheres embedded
      with magnetic and fluorescent nanoparticles and their application in adsorption
      of methylene blue.
AB  - Many efforts have been devoted towards the fabrication of multifunctional
      (mesoporous, magnetic and fluorescent) nanocomposites due to their growing
      applications as adsorbents, catalysts, and biomedical application, etc. Novel,
      flower-structured multifunctional Fe3O4/YVO4:Eu(3+)@SiO2 microspheres were
      successfully synthesized through a simple self-assembled process. The as-obtained
      products were characterized by X-ray diffraction (XRD), field emission scanning
      electron microscopy (FESEM), transmission electron microscopy (TEM), X-ray
      photoelectron spectroscopy (XPS), N2 adsorption-desorption, photoluminescence
      (PL) spectroscopy and using a vibrating sample magnetometer (VSM). The results
      reveal that the novel composites exhibit typical mesoporous structure, narrow
      size distribution, good monodispersity, excellent luminescent properties and
      superparamagnetic features. The effects of magnetic field on the luminescent
      intensity of multifunctional composites have been discussed in our manuscript.
      Furthermore, the adsorption experiments indicate that the resulting
      multifunctional composites are powerful adsorbents for the removal of methylene
      blue from water with a maximum adsorption efficiency of 98%. It is envisioned
      that multifunctional composites with high surface area are of particular interest
      for adsorption of pollutants, separation, and water purification. 

PMID- 24085333
TI  - Spin-orbit and relativistic all-electron potential energy curves for the ground
      and low-lying excited states of AgAu.
AB  - The spin-free and spin-orbit potential energy curves of ground and excited states
      of AgAu up to 5 eV have been investigated. Calculations have been performed at
      the all-electron level with scalar relativistic effects included through the
      second-order Douglas-Kroll-Hess Hamiltonian. We have used the complete active
      space multi-configuration self-consistent field method, followed by the multi
      reference configuration interaction (MRCI) calculations. Energetics and
      spectroscopic constants have been reported for all states. Our data show
      excellent agreement with the experimental measurements. Time dependent density
      functional theory calculations using the LDA, BLYP, B3LYP, and SAOP functionals
      have been carried out for AgAu and the accuracy of TD-DFT has been compared with
      ab initio results. 

PMID- 24085332
TI  - The NIMH Research Domain Criteria (RDoC) Project: implications for genetics
      research.
AB  - Heterogeneity of disorders, comorbidity across diagnoses, and reification of
      existing disease classifications are some of the challenges facing psychiatry in
      the twenty-first century. NIMH's Research Domain Criteria (RDoC) Project seeks to
      address these issues by defining basic dimensions of function that cut across
      disorders as traditionally defined and can be studied across multiple units of
      analysis, from genes to neural circuits to behaviors. The intent is to translate
      rapid progress in basic genetic, neurobiological, and behavioral research to an
      improved integrative understanding of psychopathology. In so doing, RDoC seeks to
      facilitate the development of new and/or optimally targeted treatments for mental
      disorders. The RDoC project would not have been possible without NIMH's long-term
      investment in basic research. Without the continuation of basic research, both
      related and unrelated to current RDoC domains and constructs, it will not be
      possible to sustain the RDoC effort. This article seeks to outline the
      relationship between RDoC and NIMH's ongoing support for broad-based basic
      research, from genetics to behavior. 

PMID- 24085334
TI  - Unraveling polar Diels-Alder reactions with conceptual DFT analysis and the
      distortion/interaction model.
AB  - The reaction energetics of 280 polar Diels-Alder (DA) reactions between 70
      dienophiles and 4 dienes have been studied in detail using the B3LYP/6-31G* level
      of theory, combining conceptual density functional theory (DFT) analysis and the
      distortion/interaction model. The barrier heights are governed by a fine balance
      between the energy required to distort the reactants from their initial to their
      transition state geometries (DeltaE++d) and the binding energy between the
      deformed reactants in the TS (DeltaE++i). The DeltaE++i values strongly correlate
      with the electrophilicity index, omega, which measures the stabilization energy
      when the system acquires an additional electronic charge from the environment,
      whereas the DeltaE++d was found to depend mainly on the nature of the diene,
      structural parameters of the dienophile (degree of substitution and ring size)
      and the asynchronicity of the TS. A detailed analysis to account for the
      geometrical parameters of the strained diene and dienophile moieties that
      influence the energy strain of the distorted fragments is also reported.

PMID- 24085335
TI  - Sleeping money: investigating the huge surpluses of social health insurance in
      China.
AB  - The spreading of social health insurance (SHI) worldwide poses challenges for
      fledging public administrators. Inefficiency, misuse and even corruption threaten
      the stewardship of those newly established health funds. This article examines a
      tricky situation faced by China's largest SHI program: the basic health insurance
      (BHI) scheme for urban employees. BHI accumulated a 406 billion yuan surplus by
      2009, although the reimbursement level was still low. Using a provincial level
      panel database, we find that the huge BHI surpluses are related to the
      (temporarily) decreasing dependency ratio, the steady growth of average wages,
      the extension of BHI coverage, and progress in social insurance agency building.
      The financial situations of local governments and risk pooling level also matter.
      Besides, medical savings accounts result in about one third of BHI surpluses.
      Although these findings are not causal, lessons drawn from this study can help to
      improve the governance and performance of SHI programs in developing countries. 

PMID- 24085336
TI  - Epicardial fat thickness correlates with carotid intima-media thickness, arterial
      stiffness, and cardiac geometry in children and adolescents.
AB  - To determine the association between epicardial fat thickness and carotid
      arterial stiffness, carotid intima-media thickness (CMIT), left atrial (LA)
      volume, and left-ventricular (LV) geometry parameters in obese children and
      adolescents compared with controls. A case-control study was performed in 96
      children and adolescents (obese n = 66, controls n = 30) age 9-16 years old (38
      female and 58 male, mean age 11.7 +/- 2.8 years) undergoing transthoracic
      echocardiography and carotid artery ultrasound. Clinical, anthropometric, and
      biochemical determinations were also recorded. Epicardial fat thickness (2.76 +/-
      1.2 vs. 1.36 +/- 0.7 mm, p < 0.001), LA volume (35.7 +/- 13.2 vs. 28.9 +/- 9.8
      mL, p = 0.008), LV mass (118.3 +/- 38.6 vs. 96.4 +/- 35.4 mL, p = 0.008), CIMT
      (0.48 +/- 0.07 vs. 0.44 +/- 0.05 mm, p = 0.019), and local pulse wave velocity
      (LPWV; 3.7 +/- 0.5 vs. 3.2 +/- 0.4 m/seg, p = 0.007) were significantly increased
      in obese children and adolescents compared with controls. Epicardial fat showed a
      significant and positive correlation with LA volume, LV mass, and LPWV as well as
      a significant and independent association with increased CIMT (odds ratio (OR) =
      3.19 [1.88-7.99], p = 0.005) in the study population. Epicardial fat thickness is
      linked to obesity, carotid subclinical atherosclerosis, and cardiac geometry
      parameters and might be a useful tool for the cardiovascular risk stratification
      in children and adolescents.

PMID- 24085337
TI  - How long is the yardstick for smoking bans in Switzerland?

PMID- 24085338
TI  - The effect of thrombus aspiration during primary percutaneous coronary
      intervention on clinical outcome in daily clinical practice.
AB  - It was the purpose of this study to assess the effect of thrombus aspiration (TA)
      during primary percutaneous coronary intervention (PPCI) on reperfusion and
      clinical outcome in a real-world STEMI population. The decision to use TA (Export
      catheter, Medtronic) was at the discretion of the treating cardiologist. The
      primary endpoint was mortality at short (in-hospital) and long term (one year)
      follow-up. Secondary end points were post-PCI TIMI flow, residual ST deviation
      and enzymatic infarct size. Cox proportional hazard models (propensity-weighted)
      and logistic regression analysis were used to adjust for known covariates,
      associated with mortality. We performed a retrospective analysis of prospectively
      collected data on 2,552 consecutive PPCI-treated STEMI patients between 2007 and
      2010. Use of TA increased from 6.9% in 2007 to 62.2% in 2010 (p<0.001). TA was
      performed in 899 patients (35.2%). In-hospital and one-year mortality rates were
      3.0% and 6.0%, respectively, in the TA group and 3.5% and 7.6% in the no-TA
      group. After multivariate analysis, TA was not significantly associated with in
      hospital mortality (adjusted odds ratio [OR]: 0.70; 95% confidence interval [CI]:
      0.33-1.49, p=0.36) nor one year mortality (adjusted hazard ratio [HR]: 0.75,
      95%CI: 0.47-1.20, p=0.23) or cardiac mortality (HR: 0.81; 95%CI: 0.45-1.46,
      p=0.49). After matching on the propensity score, the HR in the TA group for one
      year mortality was 0.70 (95%CI: 0.41-1.20, p=0.19) and for one-year cardiac
      mortality 0.70 (95%CI: 0.36-1.34, p=0.28). In conclusion, no significant
      relationship of TA with one of the secondary end points was found. The use of TA
      increased over the last years but clinical outcome was similar in both groups (TA
      vs no-TA) in this large cohort of real-world, unselected STEMI patients. 

PMID- 24085339
TI  - Network-based approaches for anticancer therapy (Review).
AB  - Cancer is a complex disease resulting from alterations of multiple signaling
      networks. Cancer networks have been identified as scale-free networks and may
      contain a functionally important key player called a hub that is linked to a
      large number of interactors. Since a hub can serve as a biological marker in a
      given network, targeting the hub could be an effective strategy for enhancing the
      efficacy of cancer treatment. Chemotherapies and radiotherapies are generally
      used to treat tumors not amenable to resection, and target single or multiple
      molecules associated with hubs. However, these therapies may unexpectedly induce
      the resistance of cancer cells to drugs and radiation. Cancer cells can overcome
      therapy-induced damage via the activation of back-up signaling pathways and
      flexible modulation of affected networks. These activities are considered to be
      the main reasons for chemoresistance and radioresistance, and subsequent failure
      of cancer therapies. Much effort is required to identify the key molecules that
      control the modulation of signaling networks in response to drugs and radiation.
      Network-based therapy that affects network flexibility, including rewired network
      structures and hub molecules in these networks, could minimize the occurrence of
      side-effects and be a promising strategy for enhancing the therapeutic efficacy
      of cancer treatments. This review is intended to offer an overview of current
      research efforts including ones focused on cancer-associated complex networks,
      their modulation in response to cancer therapy, and further strategies targeting
      networks that may improve cancer treatment efficacy. 

PMID- 24085340
TI  - Gene expression analysis of relapsing-remitting, primary progressive and
      secondary progressive multiple sclerosis.
AB  - BACKGROUND: Previous studies of multiple sclerosis (MS) have indicated
      differences in the pathogenesis in relapsing-remitting (RRMS), secondary
      progressive (SPMS) and primary progressive (PPMS) disease. OBJECTIVE: We
      hypothesized that different MS subtypes would show differences in gene expression
      that could be traced to specific subsets of peripheral blood mononuclear cells
      (PBMCs). METHODS: Gene expression in RRMS, SPMS, PPMS and healthy control (HC)
      PBMCs was analyzed on Affymetrix arrays. In addition, we studied gene expression
      in pools of purified PBMC subsets. RESULTS: We found 380 genes that were
      differentially expressed in RRMS, PPMS, SPMS and HCs (false discovery rate < 5%).
      There were no major differences between the subtypes of MS. The genes showing
      most prominent expression changes in RRMS were associated with adaptive immune
      pathways, while genes in PPMS were associated with innate immune system pathways.
      SPMS patients shared pathways with RRMS and PPMS patients. Gene expression
      changes were most prominent in B cells, CD8+ T cells and monocytes. CONCLUSION:
      Differences in gene expression, which could be traced to B cells, CD8+ T cells
      and monocytes, were found between MS patients and HCs but only minor differences
      were observed between MS subgroups.

PMID- 24085341
TI  - The effect of variable doses of inorganic nitrate-rich beetroot juice on
      simulated 2,000-m rowing performance in trained athletes.
AB  - CONTEXT: Beetroot juice is a naturally rich source of inorganic nitrate (NO(3-)),
      a compound hypothesized to enhance endurance performance by improving exercise
      efficiency. PURPOSE: To investigate the effect of different doses of beetroot
      juice on 2000-m ergometer-rowing performance in highly trained athletes. METHODS:
      Ten highly trained male rowers volunteered to participate in a placebo
      controlled, double-blinded crossover study. Two hours before undertaking a 2000-m
      rowing-ergometer test, subjects consumed beetroot juice containing 0 mmol
      (placebo), 4.2 mmol (SINGLE), or 8.4 mmol (DOUBLE) NO(3-). Blood samples were
      taken before supplement ingestion and immediately before the rowing test for
      analysis of plasma [NO(3-)] and [nitrite (NO(2-))]. RESULTS: The SINGLE dose
      demonstrated a trivial effect on time to complete 2000 m compared with placebo
      (mean difference: 0.2 +/- 2.5 s). A possibly beneficial effect was found with
      DOUBLE compared with SINGLE (mean difference -1.8 +/- 2.1 s) and with placebo (
      1.6 +/- 1.6 s). Plasma [NO(2-)] and [NO(3-)] demonstrated a dose-response effect,
      with greater amounts of ingested nitrate leading to substantially higher
      concentrations (DOUBLE > SINGLE > placebo). There was a moderate but
      insignificant correlation (r = -.593, P = .055) between change in plasma [NO(2-)]
      and performance time. CONCLUSION: Compared with nitratedepleted beetroot juice, a
      high (8.4 mmol NO(3-)) but not moderate (4.2 mmol NO(3-)) dose of NO(3-) in
      beetroot juice, consumed 2 h before exercise, may improve 2000-m rowing
      performance in highly trained athletes.

PMID- 24085343
TI  - Morpho-anatomical characterization of mature embryo-derived callus of rice (Oryza
      sativa L.) suitable for transformation.
AB  - The objective of this study was to morpho-anatomically characterize embryogenic
      rice calli during early induction of somatic embryogenesis of three Brazilian
      rice cultivars. Herein, we explored embryogenic units (EUs) from 2-week-old cut
      proliferated calli to verify whether they were suitable for Agrobacterium
      tumefasciens-mediated transformation. Histological analysis and scanning electron
      microscopy (SEM) were used to analyze these types of calli during early rice
      callogenesis in the cultivars BRS Primavera, BRS Bonanca, and BRS Caiapo. The
      characteristics of the embryogenic cells were preserved in the EUs, which showed
      a globular, compact structure that contained tightly packed cells and thus
      rendered the cells suitable for transformation. The EUs of BRS Caiapo also
      maintained the characteristics of the non-embryogenic callus, such as an
      elongated morphology and a lack of cellular organization. In general, the
      observations of the histological sections corresponded with those of the SEM
      images. The histological analysis suggested that all cultivars used in these
      experiments have morphogenic potential. The EUs from proliferated 2-week-old cut
      calli maintained their embryogenic features. The EUs were subjected to
      Agrobacterium-mediated transformation, which exhibited a regeneration frequency
      of 58 % for transformed hygromycin-resistant cell lines. These results show that
      EUs from proliferated 2-week-old cut calli are suitable for plant transformation.

PMID- 24085342
TI  - Sperm guidance to the egg finds calcium at the helm.
AB  - Sperm respond to multiple cues during guidance to the egg including chemical
      attractants, temperature, and fluid flow. Of these, sperm chemotaxis has been
      studied most extensively-over 100 years-but only recently has it started to be
      understood at the molecular level. The long gestation in this understanding has
      largely been due to technical limitations that include the detection of calcium
      signal dynamics in a relatively small structure-the flagellum, measurement of
      actual chemoattractant gradients, the fact that only subpopulations of sperm
      respond at any given time, and the diversity in swimming behaviors that sperm
      exhibit from different species. Today, measurements of flagellar calcium signals
      on a fast time scale, discovery of the ion channels and organelles that may
      regulate these signals, and better understanding and quantitation of sperm
      swimming behaviors involved have given more certainty to our understanding of
      sperm directional swimming and its control by characteristic, calcium-directed
      asymmetric flagellar bends. Future research will need to apply these technical
      advances to other forms of sperm guidance such as thermotaxis and rheotaxis as
      well as gaining an understanding of how the flagellar apparatus is controlled by
      calcium. 

PMID- 24085344
TI  - Micro particle image velocimetry measurements of steady diastolic leakage flow in
      the hinge of a St. Jude Medical(r) regentTM mechanical heart valve.
AB  - A number of clinical, in vitro and computational studies have shown the potential
      for thromboembolic complications in bileaflet mechanical heart valves (BMHV),
      primarily due to the complex and unsteady flows in the valve hinges. These
      studies have focused on quantitative and qualitative parameters such as velocity
      magnitude, turbulent shear stresses, vortex formation, and platelet activation to
      identify potential for blood damage. However, experimental characterization of
      the whole flow fields within the valve hinges has not yet been conducted. This
      information can be utilized to investigate instantaneous damage to blood elements
      and also to validate numerical studies focusing on the hinge's complex fluid
      dynamics. The objective of this study was therefore to develop a high-resolution
      imaging system to characterize the flow fields and global velocity maps in a BMHV
      hinge. In this study, the steady leakage hinge flow fields representing the
      diastolic phase during the cardiac cycle in a 23 mm St. Jude Medical regent BMHV
      in the aortic position were characterized using a two-dimensional micro particle
      image velocimetry system. Diastolic flow was simulated by imposing a static
      pressure head on the aortic side. Under these conditions, a reverse flow jet from
      the aortic to the ventricular side was observed with velocities in the range of
      1.47-3.24 m/s, whereas low flow regions were observed on the ventricular side of
      the hinge with viscous shear stress magnitude up to 60 N/m2. High velocities and
      viscous shearing may be associated with platelet activation and hemolysis, while
      low flow zones can cause thrombosis due to increased residence time in the hinge.
      Overall, this study provides a high spatial resolution experimental technique to
      map the fluid velocity in the BMHV hinge, which can be extended to investigate
      micron-scale flow domains in various prosthetic devices under different
      hemodynamic conditions.

PMID- 24085345
TI  - Psychometric properties of the PROMIS (r) pediatric scales: precision, stability,
      and comparison of different scoring and administration options.
AB  - OBJECTIVES: The objectives of the present study are to investigate the precision
      of static (fixed-length) short forms versus computerized adaptive testing (CAT)
      administration, response pattern scoring versus summed score conversion, and test
      retest reliability (stability) of the Patient-Reported Outcomes Measurement
      Information System (PROMIS((r))) pediatric self-report scales measuring the
      latent constructs of depressive symptoms, anxiety, anger, pain interference, peer
      relationships, fatigue, mobility, upper extremity functioning, and asthma impact
      with polytomous items. METHODS: Participants (N = 331) between the ages of 8 and
      17 were recruited from outpatient general pediatrics and subspecialty clinics. Of
      the 331 participants, 137 were diagnosed with asthma. Three scores based on item
      response theory (IRT) were computed for each respondent: CAT response pattern
      expected a posteriori estimates, short-form response pattern expected a
      posteriori estimates, and short-form summed score expected a posteriori
      estimates. Scores were also compared between participants with and without
      asthma. To examine test-retest reliability, 54 children were selected for
      retesting approximately 2 weeks after the first assessment. RESULTS: A short CAT
      (maximum 12 items with a standard error of 0.4) was found, on average, to be less
      precise than the static short forms. The CAT appears to have limited usefulness
      over and above what can be accomplished with the existing static short forms (8
      10 items). Stability of the scale scores over a 2-week period was generally
      supported. CONCLUSION: The study provides further information on the psychometric
      properties of the PROMIS pediatric scales and extends the previous IRT analyses
      to include precision estimates of dynamic versus static administration, test
      retest reliability, and validity of administration across groups. Both the
      positive and negative aspects of using CAT versus short forms are highlighted.

PMID- 24085346
TI  - Idiopathic intracranial hypertension; research progress and emerging themes.
AB  - Idiopathic intracranial hypertension (IIH) is a condition characterised by
      increased intracranial pressure of unknown cause predominantly seen in obese
      women of childbearing age and associated with a history of recent weight gain.
      The aetiology is poorly understood and there are no evidence-based guidelines on
      the management of the disease. We aim to provide a review of the recent
      literature outlining the latest advances in this field over the past few years.
      Areas of emerging interest related to the pathophysiology of IIH will be
      discussed, such as the role of obesity, adipose tissue and 11beta-hydroxysteroid
      dehydrogenase type 1. We consider the latest research on the role of venous sinus
      stenosis in IIH and ex vivo advances into cerebrospinal fluid drainage via the
      arachnoid granulation tissue. The latest techniques for optic nerve head
      evaluation and the role of optical coherence tomography will be summarised.
      Finally, we will discuss recent advances in the management of IIH, including
      weight loss, and medical and surgical treatment strategies. 

PMID- 24085349
TI  - [Hip dysplasia].

PMID- 24085348
TI  - Potential impact of self-perceived prodromal symptoms on the early diagnosis of
      Parkinson's disease.
AB  - The detection of Parkinson's disease (PD) at stages earlier than current
      diagnostic criteria allow for may increase the efficacy of disease-modifying
      therapies. Here we studied the relationship between retrospectively reported
      prodromal non-motor and motor features of PD, their pre-diagnostic presentation
      to physicians, and the extrapolated potential of an earlier diagnosis of PD
      considering early diagnostic markers detected at presence. One hundred and
      fifteen PD patients (41 women; age 63.2 +/- 8.6 years) underwent a structured
      face-to-face interview on 22 prediagnostic symptoms. Present olfactory function,
      motor symptoms, and substantia nigra hyperechogenicity (SN-h) were assessed using
      standardized tools. Most frequently self-perceived symptoms in the early and very
      early prediagnostic phase (>2, >7 years prior to diagnosis) were hyposmia (23, 10
      %), musculoskeletal pain (21, 9 %), and depression/anxiety (14, 11 %). In the
      late prediagnostic phase (<= 2 years) mild motor signs, especially asymmetric
      bradykinesia and rest tremor, increasingly dominated the self-perception. In the
      prediagnostic phase, 99 % of patients consulted a physician because of motor
      symptoms but only 36 % with non-motor symptoms, mostly pain (20 %),
      depression/anxiety (9 %), constipation, bladder urgency, insomnia, REM sleep
      behaviour disorder, sexual dysfunction, and malignant melanoma (each, <6 %).
      Assuming the potential detectability of present hyposmia, asymmetric motor
      slowing and SN-h, a triad highly specific for PD, as early as 5 years prior to
      diagnosis, up to 84 (73 %) patients could have been identified in the
      prediagnostic phase using their or their physicians' awareness of early symptoms.
      We conclude that educating the general population and physicians on the
      importance of distinct prodromal features and applying symptom-specific
      diagnostic programs can improve the early detection of PD.

PMID- 24085350
TI  - [Combined Salter-Pemberton pelvic osteotomy].
AB  - OBJECTIVE: In simple pelvic osteotomy in childhood the aim is for better lateral
      roofing, a safe centering of the femoral head and tuning between the volumes of
      the acetabulum and the femoral head. By the combination of anterior modified
      Pemberton osteotomy with dorsal osteotomy according to Salter these objectives
      can be achieved. INDICATIONS: Dysplasia of the acetabulum in patients between 2
      years old and adolescence, subluxation and dislocation of the femoral head, also
      in neurological diseases as cerebral palsy and hypercontainment in Legg-Calve
      Perthes disease. CONTRAINDICATIONS: Critically small pelvic bones in toddlers
      younger than 18 months, children with a delay in skeletal formation. In patients
      aged more than 15 years if the symphysis is too taut for an effectual pivoting of
      the acetabulum and the acetabulum has no potential for future maturing. SURGICAL
      TECHNIQUE: Surgery is carried out by making a skin incision by the iliac crest
      ending in the middle of the groin, the cartilaginous iliac apophysis is split and
      the periosteum is elevated from the medial and lateral wall of the ilium to the
      inner pelvic ring. A K-wire is used to mark the level and the center of the
      osteotomy and dorsal to the K-wire a straight osteotomy is performed with a Gigli
      saw and anteriorly an arc-shaped and tilted cut is made with a chisel. The distal
      iliac fragment is rotated widely outwards and forwards and a triangular bone
      graft is removed from the anterior part of the iliac crest. The graft is inserted
      into the opened up osteotomy, three K-wires are used to fix the desired position
      of the iliac fragments and the two halves of the iliac apophysis are sutured
      together. POSTOPERATIVE MANAGEMENT: After the operation uncooperative children
      receive a scotch cast for 4 weeks. Cooperative children are mobilized after 3
      weeks of bed rest. Partial weight-bearing is allowed after 6 weeks and full
      weight-bearing after 8-10 weeks. RESULTS: A total of 56 combined Salter-Pemberton
      pelvic osteotomies were performed in 49 patients from 1999 to 2008. The results
      of these studies demonstrate that this osteotomy is a safe and effective
      procedure which enables not only sufficient correction in classical dysplasia of
      the hip joint but also in high grade dislocation of the hip joint caused by
      cerebral palsy.

PMID- 24085351
TI  - [Tonnis and Kalchschmidt triple pelvic osteotomy].
AB  - OBJECTIVE: With three precise osteotomies it is possible to move the acetabulum
      to achieve sufficient coverage in dysplastic hips. INDICATIONS: Main indication
      is a painful dysplastic hip. Other acetabular pathologies, such as retroversion
      can also be addressed. In recent years young patients with Legg-Calve-Perthes
      disease CONTRAINDICATIONS: Patients with an arthrosis (Tonnis level 2) and
      obesity often have poor results. Therefore the combination of these parameters
      should be seen as a contraindication. SURGICAL TECHNIQUE: The operation starts
      with the patient in a lateral decubitus position. The first incision is parallel
      to the sacrotuberal ligament. The gluteus maximus muscle is spread until the
      ligament itself with its bony connection at the tuber ischiadicum is visible.
      After putting two special retractors in the foramen obturatorium and one to the
      spina ischiadica, osteotomy of the os ischium is performed from the incisura
      ischiadica to the foramen obturatorium. For the next osteotomy the os pubis is
      approached and it should be performed subperiostally. The vasa and nervus
      obturatorius and femoralis should be protected. At the os ilium the abdominal
      muscles are separated from the iliac crest. The third osteotomy has a 90 degrees 
      angle and starts at the linea terminalis and leads just below the spina iliaca
      anterior superior iliac spine. The acetabulum can now be moved with a Schanz
      screw. At this point it is necessary to elevate the os pubis while moving the
      acetabulum laterally. This prevents a lateralization and reduces the distance at
      the iliac osteotomy. The osteosynthesis is performed with screws at the os ilium
      and also at the os pubis. POSTOPERATIVE MANAGEMENT: Patients are advised to avoid
      weight bearing for 12 weeks. In the first 6 weeks they are allowed to perform a
      maximum flexion of 60 degrees . RESULTS: According to the Harris hip score 80.4 %
      of the patients showed good and very good results after 11.5 years. In cases with
      arthrosis and obesity a higher rate of poor results were found.

PMID- 24085347
TI  - Amyotrophic lateral sclerosis: an update on recent genetic insights.
AB  - Amyotrophic lateral sclerosis (ALS) is a devastating neurodegenerative disease
      affecting both upper and lower motor neurons. The prognosis for ALS is extremely
      poor, but there is a limited course of treatment with only one approved
      medication. A most striking recent discovery is that TDP-43 is identified as a
      key molecule that is associated with both sporadic and familial forms of ALS. TDP
      43 is not only a pathological hallmark, but also a genetic cause for ALS.
      Subsequently, a number of ALS-causative genes have been found. Above all, the RNA
      binding protein, such as FUS, TAF15, EWSR1 and hnRNPA1, have structural and
      functional similarities to TDP-43, and physiological functions of some molecules,
      including VCP, UBQLN2, OPTN, FIG4 and SQSTM1, are involved in a protein
      degradation system. These discoveries provide valuable insight into the
      pathogenesis of ALS, and open doors for developing an effective disease-modifying
      therapy. 

PMID- 24085352
TI  - [Operative treatment of congenital hip osteoarthritis with high hip luxation
      (Crowe type IV)].
AB  - OBJECTIVE: The aim of the therapy is mechanical and functional stabilization of
      high dislocated hips with dysplasia coxarthrosis using total hip arthroplasty
      (THA). INDICATIONS: Developmental dysplasia of the hip (DDH) in adults,
      symptomatic dysplasia coxarthrosis, high hip dislocation according to Crowe type
      III/IV, and symptomatic leg length inequality. CONTRAINDICATIONS: Cerebrospinal
      dysfunction, muscular dystrophy, apparent disturbance of bone metabolism, acute
      or chronic infections, and immunocompromised patients. SURGICAL TECHNIQUE: With
      the patient in a lateral decubitus position an incision is made between the
      anterior border of the gluteus maximus muscle and the posterior border of the
      gluteus medius muscle (Gibson interval). Identification of the sciatic nerve to
      protect the nerve from traction disorders by visual control. After performing
      trochanter flip osteotomy, preparation of the true actetabulum if possible.
      Implantation of the reinforcement ring, preparation of the femur and if necessary
      for mobilization, resection until the trochanter minor. Test repositioning under
      control of the sciatic nerve. Finally, refixation of the trochanteric crest.
      POSTOPERATIVE MANAGEMENT: During hospital stay, intensive mobilization of the hip
      joint using a continuous passive motion machine with maximum flexion of 70
      degrees . No active abduction and passive adduction over the body midline.
      Maximum weight bearing 10-15 kg for 8 weeks, subsequently, first clinical and
      radiographic follow-up and deep venous thrombosis prophylaxis until full weight
      bearing. RESULTS: From 1995 to 2012, 28 THAs of a Crow type IV high hip
      dislocation were performed in our institute. Until now 14 patients have been
      analyzed during a follow-up of 8 years in 2012. Mid-term results showed an
      improvement of the postoperative clinical score (Merle d'Aubigne score) in 86 %
      of patients. Good to excellent results were obtained in 79 % of cases. Long-term
      results are not yet available. In one case an iatrogenic neuropraxia of the
      sciatic nerve was observed and after trauma a redislocation of the arthroplasty
      appeared in another case. In 2 cases an infection of the THA appeared 8 and 15
      months after index surgery. No pseudoarthrosis of the trochanter or aseptic
      loosening was noticed.

PMID- 24085353
TI  - [Springermedizin.de -- the editor recommends].

PMID- 24085355
TI  - Introduction of interdisciplinary teaching: two case studies : commentary on
      "teaching science, technology, and society to engineering students: a sixteen
      year journey".
AB  - Interdisciplinary courses on science, engineering and society have been
      successfully established in two cases, at Bilkent University, Ankara, Turkey, and
      at the University of Hamburg, Germany. In both cases there were institutional and
      perceptual barriers that had to be overcome in the primarily disciplinary
      departments. The ingredients of success included a clear vision of
      interdisciplinary themes and didactics, and the exploitation of institutional
      opportunities. Haldun M. Ozaktas in Ankara used the dynamics of an accreditation
      process to establish courses on engineering and society. At the University of
      Hamburg the introduction of optional courses into all curricula allowed for the
      establishment of a seminar series on physics and society, as well as on peace
      education and peace building. Both of these approaches have a weakness in common:
      the courses can disappear once their initiators have left, unless the
      interdisciplinary themes are integrated into compulsory core curricula. 

PMID- 24085354
TI  - Survey on the management of orbital and intraocular tumors among oculofacial
      surgeons in the Asia-Pacific region.
AB  - A web-based anonymous survey was performed to assess the common practices of
      oculofacial surgeons in the management of orbital and intraocular tumors in the
      Asia-Pacific region. The questionnaire comprised a series of questions covering
      controversial topics sent via email to 131 oculofacial surgeons across 14
      countries in the Asia-Pacific region. A total response rate of 61.7 % was
      achieved from May to December 2012. The most common benign orbital tumor was
      cavernous hemangioma (39.6 %) and the most common malignant orbital tumor was
      lymphoma (85.7 %). 40 % of surgeons recommended orbital radiation, for which the
      most common indications were thyroid eye disease (70.0 %) and malignancy (30.0
      %). The most common orbitotomy approach was lateral (79.2 %). Most surgeons (87.1
      %) offered enucleation for retinoblastoma, but there was also a significant
      proportion that offered chemoreduction with transpupillary thermotherapy or
      cryotherapy (58.1 %). Fewer surgeons offered brachytherapy (16.1 %) and intra
      arterial chemotherapy (6.5 %). When performing enucleation for retinoblastoma,
      81.8 % of surgeons performed a primary orbital implant placement. The most
      preferred type of implant was silicone/acrylic (90.2, 90.2 and 87.8 % for
      elderly, adults and children, respectively). The majority of surgeons used donor
      sclera (57.5 %) or no wrapping material at all (32.5 %). Almost all surgeons
      (95.1 %) did not drill and peg the implant for motility. We report the results of
      the first survey of oculofacial surgeons in the Asia-Pacific region on the
      management of intraocular and orbital tumors. In comparison with previous surveys
      performed in the USA and the UK, we found the practice patterns of the Asia
      Pacific surgeons to be comparable.

PMID- 24085356
TI  - Genetic polymorphisms of XRCC3 Thr241Met (C18067T, rs861539) and bladder cancer
      risk: a meta-analysis of 18 research studies.
AB  - The relationship of bladder cancer with the presence of X-ray cross-complementing
      group 3(XRCC3) genetic polymorphism Thr241Met has been reported with inconsistent
      results. The objective of this study was to quantitatively evaluate the
      association between this polymorphism and bladder cancer susceptibility. A
      comprehensive research was conducted through PubMed, Medline, Embase, and Web of
      Science databases up to Aug. 20, 2013. Pooled odds ratio and 95 % confidence
      interval were calculated using a fixed or random effects model. Statistical
      analysis was performed with Stata 12.0 software. Of the 18 case-control studies
      selected for this meta-analysis, a total of 5,667 bladder cancer cases and 7,609
      controls were included. The combined results based on all studies suggested that
      XRCC3 Thr241Met was associated with bladder cancer risk under homozygote and
      recessive models. When stratifying for ethnicity, significant association was
      found in Caucasians under homozygote and recessive models. This meta-analysis
      suggests that XRCC3 Thr241Met polymorphism is a risk factor for bladder cancer
      risk. However, further well-designed studies are required to confirm our
      findings.

PMID- 24085359
TI  - [Clear redundancy in meta-analyses - overlapping meta-analyses can absolutely be
      useful].

PMID- 24085358
TI  - Association of CYP3A4, CYP3A5 polymorphisms with lung cancer risk in Bangladeshi
      population.
AB  - The rate of direct smoking, second hand smoking, and smokeless tobacco users as
      well as the amount of environmental pollutant like polycyclic aromatic
      hydrocarons is increasing in Bangladesh. Therefore, the prevalence of lung cancer
      is increasing day by day. To the best of our knowledge, no pharmacogentic study
      of CYP3A4, CYP3A5 genes has been reported on Bangladeshi population relating
      those with lung cancer. The present study was conducted to determine the
      association of CYP3A4, CYP3A5 gene polymorphisms and tobacco smoking in the
      development of lung cancer in Bangladeshi population. A case-control study was
      carried out on 106 lung cancer patients and 116 controls to investigate three
      allelic variants-CYP3A4*1B, CYP3A5*3, and CYP3A5*6 using Polymerase Chain
      Reaction Restriction Fragment Length Polymorphism. Risk of lung cancer was
      estimated as odds ratio (OR) and 95 % confidence interval (CI) using
      unconditional logistic regression models. The variant allele frequencies for
      CYP3A4*1B (*1A/*1B + *1B/*1B) were 2.83 % and 0.86 % and that of CYP3A5*3 (*1A/*3
      + *3/*3) were 88.68 % and 85.34 % in cases and controls, respectively. Individual
      carrying at least one variant allele of CYP3A4*1B (CYP3A4*1A/1B + *1B/1B) has a
      3.35 times more risk (OR = 3.35, 95 % Cl = 0.34-32.71, p = 0.271) for developing
      lung cancer whereas individual carrying at least one variant allele of CYP3A5
      (CYP3A5*1A/3 + *3/3) has a 1.26 times more risk (OR = 1.35, 95 % Cl = 0.61-2.97)
      and both are statistically non-significant (p > 0.05). CYP3A5*6 was absent in the
      study population. No association of lung cancer with the mentioned polymorphisms
      was found both in heavy and light smokers. In the cases of all three major types
      of lung cancer-squamous cell carcinoma, adenocarcinoma, and small cell carcinoma
      significantly strong relationships (p ? 0.05) have been found. To confirm the
      association of lung cancer with the mentioned polymorphisms, large number
      volunteers (patients and controls) will be required.

PMID- 24085360
TI  - [Successful cancer therapy: chance and challenges].

PMID- 24085357
TI  - Smoking and hOGG1 Ser326Cys polymorphism contribute to lung cancer risk: evidence
      from a meta-analysis.
AB  - The human 8-oxoguanine DNA glycosylase (hOGG1) gene plays an important role in
      the repair of oxidatively damaged DNA base lesions and its functional single
      nucleotide polymorphisms (SNPs) may alter DNA repair capacity and thus
      contributes to cancer susceptibility. Numerous studies have investigated the
      association between hOGG1 Ser326Cys polymorphism and lung cancer susceptibility;
      however, the conclusions are still inconclusive. We searched eligible
      publications from MEDLINE, EMBASE, and CBM and performed a meta-analysis to
      assess the associations between hOGG1 Ser326Cys polymorphism and lung cancer
      risk. Pooled odds ratios (ORs) and 95 % confidence intervals (CIs) were
      calculated to estimate risk associations, and false-positive report probability
      (FPRP) analysis was also carried out to evaluate significant findings. A total of
      31 investigations with 10,220 cases and 12,284 controls were identified. When all
      studies were pooled, a significantly increased overall lung cancer risk was found
      (Cys/Cys vs. Ser/Ser: OR = 1.24, 95 % CI = 1.05-1.47, P = 0.013; recessive model:
      OR = 1.22, 95 % CI = 1.05-1.41, P = 0.008, and Cys vs. Ser: OR = 1.11, 95 % CI =
      1.02-1.21, P = 0.022), and further stratification analysis showed that the
      association was stronger in Asians, never smokers, and more-cigarette takers.
      These results were confirmed by FPRP analysis. Despite some limitations, this
      meta-analysis provides solid evidence that hOGG1 Ser326Cys polymorphism may
      contribute to lung cancer risk, particularly for Asian populations, never
      smokers, and more-cigarette takers. Nevertheless, these findings warrant further
      validation in single large investigations.

PMID- 24085361
TI  - [Primary pharmacological prevention of thromboembolic events in ambulatory
      patients with advanced pancreatic cancer treated with chemotherapy?].
AB  - BACKGROUND AND OBJECTIVE: The indication for medical venous thrombosis
      prophylaxis in ambulatory cancer patients is still under discussion. To provide
      more data on this topic we conducted an analysis in ambulatory patients with
      advanced pancreatic adenocarcinoma, reflecting a patient cohort at high risk of
      symptomatic venous thromboembolism (sVTE). PATIENTS AND METHODS: Data from 312
      consecutively recruited patients of the CONKO-004 trial were analysed according
      to predefined parameters and additionally with respect to established scores. To
      focus on patients with highest risk of sVTE unvaried and multivariate analyses
      were conducted. RESULTS: The global analyses had educed a number needed to treat
      (NNT) by medical thrombosis prophylaxis of 12 patients to prevent one sVTE. The
      modified score model did not provide further clinical benefit. However, the
      regression model can identify single parameters with a trend to higher risk of
      sVTE or higher risk of severe bleeding. Most of the parameters do not have enough
      power to be significant, but they can support clinical decisions. CONCLUSION:
      These data suggest that medical thrombosis prophylaxis should be performed in
      patients with advanced pancreatic cancer at least for the initial 3 months of
      first line chemotherapy.

PMID- 24085362
TI  - [71-year old woman with neutropenic fever during chemotherapy].

PMID- 24085363
TI  - [Autoimmune hemolysis accompanied by thrombopenia: consumption or
      myelodysplasia?].
AB  - HISTORY: A 77-year-old patient with a known autoimmune hemolysis for years was
      treated with steroids, rituximab, cyclophosphamid, cyclosporin A. Because of
      accompanying thrombopenia he received eltrombopag and underwent splenectomy but
      without lasting effect. After 3 years he presented with decreased leukocytes and
      worsening of thrombopenia. INVESTIGATIONS: A peripheral blood count showed
      moderate pancytopenia without blasts or left shift. Bone marrow biopsy revealed
      myelodysplasia with excessive blasts, cytogenetics showed partial trisomy 18q.
      TREATMENT AND COURSE: Because of the high risk of transformation to acute myeloid
      leukemia treatment with 5-azacytidine was started. Thrombopenia rapidly improved,
      but after an infectious complication treatment was paused for several months due
      to patient wish. Treatment was started again after 11 months because of
      progressive thrombopenia and resulted in a rapid hematological improvement.
      CONCLUSION: The new diagnosis of a myelodysplastic syndrome should be considered
      in the case of new cytopenia even in the presence of an already established
      hematological disease.

PMID- 24085364
TI  - [Are the new breast cancer subtypes (luminal A, B etc.) of practical impact?
      Yes].

PMID- 24085365
TI  - [Are the new breast cancer subtypes (luminal A, B etc.) of practical impact? No].

PMID- 24085366
TI  - [Treatment of colorectal liver metastases].
AB  - The treatment of patients with colorectal liver metastases has been changed with
      the improved surgical techniques and the increasingly effective systemic therapy.
      It represents therefore a model for the therapy in other situations with limited
      metastatic disease. Because the overall survival is associated with
      metastasectomy, the treatment of patients with liver metastases should be
      discussed in a team with experienced liver surgeons. Options to increase or to
      achieve resectability are especially "conversion" chemotherapy, but also i. e.
      portal vein embolization and two step resections. 

PMID- 24085367
TI  - [Chemotherapy-free treatment of chronic lymphocytic leukemia?].
AB  - Treatment of CLL patients with conventional cytotoxic agents is often combined
      with significant toxicity that prevents broad application especially in elderly
      patients. In addition, relapse frequently occurs after application of
      conventional chemotherapy in CLL. Recently several new chemo-free treatment
      options have been introduced within clinical trials. Among them are monoclonal
      antibodies, most of them targeting the CD20 molecule: besides the licensed drugs
      rituximab and ofatumumab obinutuzumab, although in combination with chemotherapy,
      has recently shown high clinical efficacy in front-line treatment of elderly
      patients with CLL. Lenalidomide as monotherapy has demonstrated clinical efficacy
      in patients with relapsed disease and first data within clinical trials have been
      generated in the front-line setting. A promising class of novel agents has been
      designed to block aberrant signaling from the B-cell receptor. Ibrutinib acts by
      inhibiting the Bruton's tyrosine kinase (BTK) while idelalisib represents a first
      in-class specific inhibitor of the phosphoinositol-3 kinase (PI3K) delta isoform.
      Another class of drugs with potential impact for chemo-free treatment strategies
      in CLL are the BH3-mimetic inhibitors of the Bcl-2 family of pro-survival
      proteins. Other interesting candidate drugs that are currently explored for CLL
      patients include small modular immunopharmaceutical (SMIP) proteins (e. g. TRU
      016), CDK inhibitors (e. g. dinaciclib), HDAC inhibitors and others. Given all
      these novel agents and targets, chemo-free or at least chemo-reduced concepts may
      become reality in the near future for our patients suffering from CLL. 

PMID- 24085368
TI  - [Adjuvant chemotherapy for soft tissue sarcoma? a clear no - well - yes-ish].

PMID- 24085369
TI  - [Hans Hirschfeld - nestor of hematology].

PMID- 24085370
TI  - [Why isn't orciprenaline approved as antiarrhythmic agent?].

PMID- 24085371
TI  - Age--an independent prognostic factor of clinical outcome in renal malignancies:
      results of a large study over two decades.
AB  - PURPOSE: Age has been linked to outcome in renal cancer patients, but mainly in
      North American cohorts. In this study, we hypothesized that age is correlated
      with metastasis and cancer-specific survival in a German cohort regardless of
      types of treatments. METHODS: A total of 1,538 patients treated for renal
      malignancies between 1991 and 2010 were evaluated. Mean age and median age are
      61.9 +/- 11.6 and 62.6 years. Clinicopathologic [tumor type, size, grade, stage
      and treatment (surgery, chemotherapy, radiation, immunotherapy)] and outcome
      parameters (metastasis and survival) were examined for an association with age
      using logistic regression and Cox proportional hazard model, and Kaplan-Meier
      plots. RESULTS: Age was associated with stage, metastasis, treatment, cancer
      specific and overall mortality (p < 0.01). The metastasis-free and cancer-free
      survival rates for patients >63 years were lower than those for patients <=63
      years (p < 0.0001). In a multivariate analysis, age was an independent prognostic
      factor of metastasis, cancer-specific and overall mortality (p < 0.0001) even
      when data were stratified in different decades and treatment was included as one
      of the parameters. Patients >63 years of age had 29-35% higher risk of metastasis
      and cancer-specific mortality than younger patients. Median metastasis-free and
      cancer-specific survival for patients >63 years of age (months: 84.4; 70.3) was
      ~50% shorter than in patients <=63 years (months: 151; 144.6). CONCLUSIONS: This
      large study shows that, despite advances in surgical and non-surgical treatment
      modalities over the two decades, age is an independent prognostic indicator of
      metastasis and cancer-specific mortality in renal cancer patients. Patients >63
      years have ~30% increased risk for metastasis and ~50% shorter cancer-specific
      survival.

PMID- 24085373
TI  - Phase selection during the crystallization of metal-organic frameworks;
      thermodynamic and kinetic factors in the lithium tartrate system.
AB  - We report the phase behaviour of chiral, racemic and meso-lithium tartrate
      frameworks, which was examined as a function of solvent system, temperature and
      ligand isomer. Through our comprehensive investigation of this system of 14
      diverse phases, we have gained detailed insight into the effect of synthesis
      conditions on product structure, and elucidated the thermodynamic and kinetic
      factors involved in phase selection. Reactions in ethanol between lithium acetate
      and chiral, racemic and meso-tartaric acids give rise to anhydrous kinetic
      products; polymorphs with higher entropy tend to appear at high temperatures.
      Reactions at room temperature in water-ethanol mixtures give rise to hydrated
      kinetic products, including two new crystal structures, [Li2(D,L
      tartrate)(H2O)2]n in P1 and [Li2(meso-tartrate)(H2O)(0.5)]n in C222(1), whose
      structures are contrasted with known anhydrous products. Reactions at elevated
      temperatures in water-ethanol mixtures result in the formation of low enthalpy,
      anhydrous products and, furthermore, the global minimum energy structure appears
      at high temperatures in all cases owing to in situ ligand isomerization.

PMID- 24085372
TI  - Oligodendroglioma cells synthesize the differentiation-specific linker histone H1
      and release it into the extracellular environment through shed vesicles.
AB  - Chromatin remodelling can be involved in some of the epigenetic modifications
      found in tumor cells. One of the mechanisms at the basis of chromatin dynamics is
      likely to be synthesis and incorporation of replacement histone variants, such as
      the H1 linker histone. Regulation of the expression of this protein can thus be
      critical in tumorigenesis. In developing brain, H1 expression is mainly regulated
      at the post-transcriptional level and RNA-binding proteins (RBPs) are involved.
      In the past, attention mainly focused on the whole brain or isolated neurons and
      little information is available on H1 expression in other brain cells. Even less
      is known relating to tumor glial cells. In this study we report that, like in
      maturing brain and isolated neurons, H1 synthesis sharply increases in
      differentiating astrocytes growing in a serum-free medium, while the
      corresponding mRNA decreases. Unexpectedly, in tumor glial cells both H1 RNA and
      protein are highly expressed, in spite of the fact that H1 is considered a
      differentiation-specific histone variant. Persistence of H1 mRNA in
      oligodendroglioma cells is accompanied by high levels of H1 RNA-binding
      activities which seem to be present, at least in part, also in actively
      proliferating, but not in differentiating, astrocytes. Finally, we report that
      oligodendroglioma cells, but not astrocytes, release H1 protein into the culture
      medium by shedding extracellular vesicles. These findings suggest that
      deregulation of H1 histone expression can be linked to tumorigenesis. 

PMID- 24085374
TI  - Impairment of 40-km time-trial performance but not peak power output with
      external iliac kinking: a case study in a world-class cyclist.
AB  - Iliac blood-flow restrictions causing painful and "powerless" legs are often
      attributed to overtraining and may develop for some time before being correctly
      diagnosed. In the current study, differences between actual performance
      parameters and performance parameters predicted from the Lamberts and Lambert
      Submaximal Cycle Test (LSCT) were studied in a world-class cyclist with bilateral
      kinking of the external iliac artery before and after surgery. Two performance
      testing sessions, including a peak-power-output (PPO) test and a 40-km time trial
      (TT) were conducted before surgery, while 1 testing session was conducted after
      the surgery. Actual vs LSCT-predicted performance parameters in the world-class
      cyclists were compared with 82 symptom-free trained to elite male cyclists. No
      differences were found between actual and LSCT-predicted PPO before and after
      surgical intervention. However, there were differences between actual and LSCT
      predicted 40-km TT time in the tests performed before the surgery (2:51and 2:55
      min:s, respectively). These differences were no longer apparent in the
      postsurgery 40-km TT (2 s). This finding suggests that iliac blood-flow
      restrictions seem to mainly impair endurance performance rather than peak cycling
      performance. A standard PPO test without brachial ankle blood-pressure
      measurements might not be able to reflect iliac blood-flow restrictions.
      Differences between actual and LSCT-predicted 40-km TT time may assist in earlier
      referral to a cardiovascular specialist and result in earlier detection of iliac
      blood-flow restrictions. 

PMID- 24085375
TI  - Risk and protective factors for retention in HIV care.
AB  - Retention in care for HIV is essential for effective disease management; however,
      factors that may confer risk or protection for adherence to regular HIV care are
      less well understood. This study tested whether HIV-associated cognitive
      impairment (CI) and low health literacy reduced adherence to routine HIV medical
      and phlebotomy visits and if social support and patient-provider relationship
      conferred a protective effect. Participants were 210 HIV-infected patients
      enrolled in outpatient care and followed for 28-weeks. Results showed that those
      attending >75 % of phlebotomy visits were more likely to be virally suppressed.
      Health literacy was unassociated with adherence to medical or phlebotomy visits.
      CI was not directly related to medical or phlebotomy visit adherence; however
      those with CI and greater use of social support were less likely to miss medical
      visits. Utilizing social support may be an effective means of managing visit
      adherence, especially among patients with CI.

PMID- 24085376
TI  - Diffusion-weighted imaging and diagnosis of transient ischemic attack.
AB  - OBJECTIVE: Magnetic resonance (MR) diffusion-weighted imaging (DWI) is sensitive
      to small acute ischemic lesions and might help diagnose transient ischemic attack
      (TIA). Reclassification of patients with TIA and a DWI lesion as "stroke" is
      under consideration. We assessed DWI positivity in TIA and implications for
      reclassification as stroke. METHODS: We searched multiple sources, without
      language restriction, from January 1995 to July 2012. We used PRISMA guidelines,
      and included studies that provided data on patients presenting with suspected TIA
      who underwent MR DWI and reported the proportion with an acute DWI lesion. We
      performed univariate random effects meta-analysis to determine DWI positive rates
      and influencing factors. RESULTS: We included 47 papers and 9,078 patients (range
      = 18-1,693). Diagnosis was by a stroke specialist in 26 of 47 studies (55%); all
      studies excluded TIA mimics. The pooled proportion of TIA patients with an acute
      DWI lesion was 34.3% (95% confidence interval [CI] = 30.5-38.4, range = 9-67%;
      I(2)  = 89.3%). Larger studies (n > 200) had lower DWI-positive rates (29%; 95%
      CI = 23.2-34.6) than smaller (n < 50) studies (40.1%; 95% CI = 33.5-46.6%; p =
      0.035), but no other testable factors, including clinician speciality and time to
      scanning, reduced or explained the 7-fold DWI-positive variation. INTERPRETATION:
      The commonest DWI finding in patients with definite TIA is a negative scan.
      Available data do not explain why 2/3 of patients with definite specialist
      confirmed TIA have negative DWI findings. Until these factors are better
      understood, reclassifying DWI-positive TIAs as strokes is likely to increase
      variance in estimates of global stroke and TIA burden of disease.

PMID- 24085378
TI  - Analysis of effectiveness of therapeutic exercise for knee osteoarthritis and
      possible factors affecting outcome.
AB  - BACKGROUND: There are numerous reports and evidences to suggest that exercise
      therapy is effective for knee osteoarthritis (knee OA). However, there is a lack
      of sufficient research concerning the factors influencing its application and
      effectiveness. The purposes of this study were to evaluate effects of the mode of
      treatment delivery on the improvement of symptoms in knee OA, and to analyze
      potential risk factors affecting improvement after exercise therapies. METHODS:
      The 209 women applicants diagnosed with knee OA were randomly allocated into
      either a group performing group exercise in a class or a group performing home
      exercise. The 90 min exercise program was performed under the guidance of
      physiotherapists as a group exercise therapy. The Western Ontario and McMaster
      Universities Osteoarthritis Index (WOMAC) of the subjects of both groups before
      and after intervention was compared to examine the effect of exercise therapy. In
      addition, body mass index, knee range of motion (ROM), the femorotibial angle
      from radiographs, OA severity from Kellgren-Lawrence grade, and meniscus
      abnormality and subchondral bone marrow lesions from MRI findings were
      statistically analyzed as factors that may affect exercise therapy. RESULTS: A
      significantly greater improvement in WOMAC was observed in the subjects of group
      exercise (81 subjects) as compared with the subjects of home exercise (122
      subjects). There was a significantly high proportion of subjects with knee
      flexion contracture among the subjects participating in group exercise that
      showed only minor symptom improvement (p < 0.05). In addition, exercise therapy
      proved to be highly effective for subjects with limited quadriceps muscle
      strength (p < 0.05). CONCLUSIONS: When prescribing exercise therapy for knee OA,
      evaluation of a subject's ROM and muscle strength is important in deciding
      whether to commence exercise therapy and what type of exercise therapy to apply;
      it is also important in predicting the effect of exercise therapy.

PMID- 24085379
TI  - Reproductive toxicity in adult male rats following intra-articular injection of
      cobalt-chromium nanoparticles.
AB  - BACKGROUND: Recent studies have reported that metallic nanoparticles and ions
      from cobalt-chromium (CoCr) alloy prostheses had potential adverse effects.
      However, the biological effects of CoCr nanoparticles on male reproductive
      function remain unclear. The objective of this study is to investigate the
      reproductive toxicity in adult male rats following intra-articular injection of
      cobalt-chromium nanoparticles. METHODS: CoCr nanoparticles were generated by a
      spark discharge method. Adult male rats received intra-articular injections of
      CoCr nanoparticles once a week at a low (20 MUg/kg b.w.), medium (100 MUg/kg
      b.w.) or high dose (500 MUg/kg b.w.) for 10 consecutive weeks. The control group
      received intra-articular injections of physiological saline. After the final
      injection, all rats were held for a 7-day post-exposure period. The effects on
      male reproductive function were observed, including the coefficient of testicular
      to body weight, the epididymal sperm parameters, the concentration of metal ions
      in serum and testis, the activity of antioxidase and the content of lipid
      peroxide in the testis, and histopathological examination. RESULTS: Compared with
      the control group, intra-articular injection of high dose CoCr nanoparticles
      could significantly reduce epididymal sperm motility, viability and
      concentration, increase abnormal sperm rate and levels of Co and Cr ions in serum
      and in the testis, and induce testicular damage and pathological changes via
      oxidative stress. CONCLUSIONS: Intra-articular injection of high dose CoCr
      nanoparticles from MOM articulation may have potential reproductive toxicity in
      adult male rats.

PMID- 24085380
TI  - Percutaneous compression plate versus proximal femoral nail anti-rotation in
      treating elderly patients with intertrochanteric fractures: a prospective
      randomized study.
AB  - BACKGROUND: The treatment and management of hip fracture poses a great challenge
      for clinicians in osteology and surgery. The aim of this study is to compare the
      clinical effectiveness of the percutaneous compression plate (PCCP) versus
      proximal femoral nail anti-rotation (PFNA) in the treatment of intertrochanteric
      fractures in elderly patients. METHODS: A prospective randomized study was
      carried out from January 2008 to October 2011 involving 90 elderly patients with
      intertrochanteric fractures (90 hips) who underwent minimally invasive surgery
      using the PCCP or PFNA. Evaluation variables, including operation time, intra-
      and perioperative blood loss, duration of hospital stay, incidence of
      postoperative complications, and final clinical outcomes by the end of follow-up,
      were used to compare the benefits of these two implants. RESULTS: Among 90
      subjects, 45 received PCCPs and 45 received PFNAs. The baseline characteristics
      of the two groups were comparable. The median follow-up time was 16.9 months (12
      24 months). In the PCCP group, the mean operative time was 53 min (40-75 min),
      and the mean intra- and perioperative blood losses were 100.7 ml (60-150 ml) and
      916 ml (433-1339 ml), respectively, which were significantly lower than those in
      the PFNA group. Nevertheless, there was no statistical difference in the
      incidence of postoperative complications and final clinical outcomes including
      pain complaints, range of motion of the hip, postoperative hip function at 12
      months, and the recovery of walking ability to pre-injury status between these
      two implants. CONCLUSIONS: Overall, the PCCP and PFNA appear to have similar
      clinical effects in treating elderly patients with intertrochanteric fractures,
      although the PCCP provided shorter operation times and less blood loss than PFNA.
      Both implants discussed were demonstrated to be ideal for the treatment of
      femoral intertrochanteric fractures in elderly patients.

PMID- 24085383
TI  - Energetics of beta-turn formation in a mutant peptide YPGDV from influenza
      hemagglutinin: an MD simulation study.
AB  - Reverse turns play an important role in protein folding, molecular recognition
      and in eliciting immune response. While sequence determinants of reverse turns
      are known, not much is known about their energetics. In this paper we have
      investigated the thermodynamics of a reverse turn sequence YPGDV, an
      experimentally well characterized turn sequence, using molecular dynamics
      simulations performed over a range of temperatures from 280-360 K using GROMACS
      4.0.4 software and all atom OPLS-AA/L force field. The change in folding free
      energy (DeltaAfolding) for the beta-turn formation in YPGDV peptide shows a
      linear relationship with temperature. We find that the entropy change
      (DeltaSfolding) for the beta-turn formation is close to zero and the internal
      energy change (DeltaUfolding) is a modest -3.8 kJ mol(-1). These thermodynamic
      quantities are interpreted in terms of intra-molecular (intra-peptide) and inter
      molecular (peptide-solvent) hydrogen bonding interactions. Implications for
      protein folding and peptide immunogenicity are discussed. 

PMID- 24085382
TI  - Circulating CD45+/CD3+ lymphocyte-derived microparticles map lipid-rich
      atherosclerotic plaques in familial hypercholesterolaemia patients.
AB  - Circulating microparticles (cMPs) seem to play important roles in vascular
      function. Beyond markers of activated cells, cMPs may have potential paracrine
      functions and influence atherosclerosis. Here, our objective was to characterise
      a) the abundance and phenotype of cMPs in stable statin-treated heterozygous
      familial hypercholesterolaemia (FH) patients exposed to life-long
      hypercholesterolaemia and b) the principal phenotype associated to lipid-rich
      atherosclerotic plaques in hFH-patients with significant atherosclerotic plaque
      burden. An age/gender/treatment-matched group of adult-onset non-FH
      hypercholesterolaemic patients (n=37/group) was comparatively analysed. cMPs were
      characterised by flow cytometry using annexin-V and cell surface-specific
      antibodies. Our study shows that LLT-FH patients had higher overall cMP-numbers
      (p<0.005) than LLT-non-FH patients. Endothelial cell-shed cMPs were also
      significantly higherin FH (p<0.0005). Within the leukocyte-derived cMP
      subpopulations, FH-patients had significantly higher lymphocyte- and monocyte
      derived cMP-numbers as well as cMPs carrying leukocyte-activation markers.
      Normalisation of cMPs by LDL levels did not affect cMP number or phenotype,
      indicating that the proinflammatory effect was derived from chronic vascular
      damage. Levels of AV+-total, CD45+-pan-leukocyte and CD45+/CD3+-lymphocyte
      derived cMPs were significantly higher in FH-patients with subclinical lipid-rich
      atherosclerotic plaques than fibrous plaques. Levels of CD45+/CD3+-lymphocyte-MPs
      above 20,000/ml could differentiate between FH-patients with lipidic or non
      lipidic plaques (area under the ROC curve of 0.803, 95%CI: 0.641-0.965, p=0.008).
      In summary, in this snapshot cross-sectional study cMP concentration and
      phenotype in FH differed markedly from non-FH hypercholesterolaemia. Patients
      with life-long high LDL exposure have higher endothelial activation and higher
      proinflammatory profile, even under current state-of-the-art LLT. cMPs carrying
      lymphocyte-epitopes appear as markers of lipid-rich atherosclerotic plaques in
      FH. 

PMID- 24085381
TI  - Autophagy as a crosstalk mediator of metabolic organs in regulation of energy
      metabolism.
AB  - Autophagy plays an important role in the regulation of cellular homeostasis
      through elimination of aggregated proteins, damaged organelles, and intracellular
      pathogens. Autophagy also contributes to the maintenance of energy balance
      through degradation of energy reserves such as lipids, glycogen, and proteins in
      the setting of increased energy demand. Recent studies have suggested that
      autophagy, or its deficiency, is implicated in the pathogenesis of insulin
      resistance, obesity, and diabetes. These effects of autophagy or its deficiency
      in regulation of energy metabolism are mediated not only by cell-autonomous
      effects, such as direct autophagic degradation of energy stores or intracellular
      organelles (endoplasmic reticulum and mitochondria) but also by non-cell
      autonomous effects, such as induction/suppression of secreted factors or changes
      of sympathetic tone. In the present review, we highlight a recent surge in the
      research on the autophagy in the regulation of energy homeostasis, with a focus
      on its role as a mediator for crosstalk between metabolic organs. 

PMID- 24085385
TI  - Organisms for biofuel production: natural bioresources and methodologies for
      improving their biosynthetic potentials.
AB  - In order to relieve the pressure of energy supply and environment contamination
      that humans are facing, there are now intensive worldwide efforts to explore
      natural bioresources for production of energy storage compounds, such as lipids,
      alcohols, hydrocarbons, and polysaccharides. Around the world, many plants have
      been evaluated and developed as feedstock for bioenergy production, among which
      several crops have successfully achieved industrialization. Microalgae are
      another group of photosynthetic autotroph of interest due to their superior
      growth rates, relatively high photosynthetic conversion efficiencies, and vast
      metabolic capabilities. Heterotrophic microorganisms, such as yeast and bacteria,
      can utilize carbohydrates from lignocellulosic biomass directly or after
      pretreatment and enzymatic hydrolysis to produce liquid biofuels such as ethanol
      and butanol. Although finding a suitable organism for biofuel production is not
      easy, many naturally occurring organisms with good traits have recently been
      obtained. This review mainly focuses on the new organism resources discovered in
      the last 5 years for production of transport fuels (biodiesel, gasoline, jet
      fuel, and alkanes) and hydrogen, and available methods to improve natural
      organisms as platforms for the production of biofuels.

PMID- 24085384
TI  - An update on liver surgery for cholangiocarcinoma.
AB  - Cholangiocarcinoma is a malignant neoplasm that originates from biliary
      epithelial cells. Complete tumor resection remains the most effective treatment
      of intra-hepatic or perihilar cholangiocarcinomas (PHCs). The objectives of this
      are to update and discuss methods that are likely to increase the resectability
      of cholangiocarcinomas, and to define the limits beyond which the risks of the
      treatments outweigh their benefits. We analyzed intra-hepatic cholangiocarcinomas
      and PHCs separately to determine the site of origin and the resectability of the
      tumor. We discussed the site at which to perform hepatic optimization prior to
      surgery, and whether liver transplantation might affect cholangiocarcinoma
      treatment. 

PMID- 24085386
TI  - Impact of photodynamic inactivation (PDI) using the photosensitizer chlorin e6 on
      viability, apoptosis, and proliferation of human keratocytes in vitro.
AB  - BACKGROUND: Photodynamic inactivation (PDI) may be a potential alternative in
      cases of therapy-resistant infectious keratitis. The purpose of our study was to
      determine the impact of PDI using the photosensitizer chlorin e6 (Ce6) on
      viability, apoptosis, and proliferation of human keratocytes, in vitro. METHODS:
      Primary human keratocytes were isolated by digestion in collagenase (1 mg/ml)
      from human corneal buttons, and cultured in DMEM/Ham's F12 medium supplemented
      with 10 % FCS. Keratocyte cell cultures underwent illumination using red (670 nm)
      light for 13 min following exposure to 50 nM to 64 MUM concentrations of Ce6 in
      the culture medium. Twenty-four hours after PDI, cell viability was evaluated by
      the Alamar blue assay, total DNA content of the cells and apoptosis using the APO
      DIRECT Kit, and cell proliferation by the BrdU Cell Proliferation Assay Kit.
      RESULTS: Using Ce6 or illumination only, we did not detect significant changes of
      cell viability, apoptosis, and proliferation. Using illumination, viability of
      keratocytes decreased significantly above 100 nM (P < 0.01), and proliferation at
      250 nM Ce6 concentration (P = 0.01) and the percentage of apoptotic keratocytes
      increased significantly at 500 nM (P < 0.01) concentration. CONCLUSIONS: In the
      short term, photodynamic inactivation using Ce6 decreases viability and
      proliferation, and also triggers apoptosis of human keratocytes, in vitro.

PMID- 24085387
TI  - Effect of physical and chemical properties of oil palm empty fruit bunch,
      decanter cake and sago pith residue on cellulases production by Trichoderma
      asperellum UPM1 and Aspergillus fumigatus UPM2.
AB  - The effect of cultivation condition of two locally isolated ascomycetes strains
      namely Trichoderma asperellum UPM1 and Aspergillus fumigatus UPM2 were compared
      in submerged and solid state fermentation. Physical evaluation on water
      absorption index, solubility index and chemical properties of lignin,
      hemicellulose and cellulose content as well as the cellulose structure on
      crystallinity and amorphous region of treated oil palm empty fruit bunch (OPEFB)
      (resulted in partial removal of lignin), sago pith residues (SPR) and oil palm
      decanter cake towards cellulases production were determined. Submerged
      fermentation shows significant cellulases production for both strains in all
      types of substrates. Crystallinity of cellulose and its chemical composition
      mainly holocellulose components was found to significantly affect the total
      cellulase synthesis in submerged fermentation as the higher crystallinity index,
      and holocellulose composition will increase cellulase production. Treated OPEFB
      apparently induced the total cellulases from T. asperellum UPM1 and A. fumigatus
      UPM2 with 0.66 U/mg FPase, 53.79 U/mg CMCase, 0.92 U/mg beta-glucosidase and 0.67
      U/mg FPase, 47.56 U/mg and 0.14 U/mg beta-glucosidase, respectively. Physical
      properties of water absorption and solubility for OPEFB and SPR also had shown
      significant correlation on the cellulases production.

PMID- 24085388
TI  - Reliable ratings or reading tea leaves: can parent, teacher, and clinician
      behavioral ratings of preschoolers predict ADHD at age six?
AB  - To assess the relative ability of parent, teacher, and clinician behavioral
      ratings of preschoolers to predict ADHD severity and diagnosis at 6 years of age.
      Hyperactive/inattentive preschoolers [N = 104, 75 % boys, Mean (SD) age = 4.37
      (0.47) years] were followed over 2 years (mean = 26.44 months, SD = 5.66). At
      baseline (BL), parents and teachers completed the ADHD-RS-IV and clinicians
      completed the Behavioral Rating Inventory for Children following a psychological
      testing session. At age 6, [Mean (SD) age = 6.62 (0.35) years], parents were
      interviewed with the K-SADS-PL; teachers completed the ADHD-RS-IV; and laboratory
      measures of hyperactivity, impulsivity, and inattention were obtained from
      children. Hierarchical logistic and linear regression analyses examined which
      combination of BL ratings best predicted 6-year-old ADHD diagnosis and severity,
      respectively. At age 6, 56 (53.8 %) children met DSM-IV criteria for a diagnosis
      of ADHD. BL ratings from parent/teacher/clinician, parent/teacher and
      parent/clinician combinations significantly predicted children who had an ADHD
      diagnosis at age 6. Parent and clinician, but not teacher, behavior ratings were
      significant independent predictors of ADHD diagnosis and severity at 6-years-old.
      However, only clinician reports of preschoolers' behaviors predicted laboratory
      measures of over-activity and inattention at follow-up. Cross-situationality is
      important for a diagnosis of ADHD during the preschool years. Among parents,
      teachers and clinicians, positive endorsements from all three informants,
      parent/teacher or parent/clinician appear to have prognostic value. Clinicians'
      ratings of preschoolers' inattention, impulsivity and hyperactivity are valid
      sources of information for predicting ADHD diagnosis and severity over time. 

PMID- 24085389
TI  - Low omentin-1 levels are related with clinical and metabolic parameters in obese
      children.
AB  - This is the first clinical study evaluating the relation of serum omentin 1
      levels with anthropometric and metabolic parameters in obese children with a
      particular interest to identify the possible role of omentin 1 in childhood
      obesity and related metabolic disturbances.The study included obese children with
      a body mass index (BMI)>95th percentile and healthy children with a BMI<85th
      percentile. The healthy and obese subjects had similar age and gender
      distribution. Glucose, insulin, lipid profile, and omentin 1 levels were measured
      to evaluate the metabolic parameters.49 obese children who applied to our
      department with complaint of weight gain and 30 healthy age and sex matched
      subjects were enrolled. In obese children BMI, body mass index-standard deviation
      score (BMI-SDS), systolic blood pressure (SBP), diastolic blood pressure (DBP),
      mid-arm circumference (MAC), triceps skin fold (TSF), waist circumference (WC),
      homeostasis model assessment-insulin resistance (HOMA-IR), serum insulin, and
      triglyceride levels were higher whereas omentin-1 levels were lower than control
      subjects (p<0.05). In the obese group, omentin 1 level was negatively correlated
      with BMI, insulin, HOMA-IR, and WC, while no significant correlation was observed
      with other parameters (p>0.05). Additionally, although statistically
      insignificant, patients with IR (n=31) had lower omentin-1 levels compared to
      obese children without IR (n=18).Our data indicates that serum omentin 1 levels
      are i) lower in obese children and ii) negatively correlated with BMI, WC, HOMA
      IR and insulin levels suggesting that omentin 1 might be a biomarker for
      metabolic dysfunction also in childhood and adolescence. Lower omentin 1 levels
      tended to be associated with insulin resistance however this association failed
      to reach statistical significance. Further studies in larger populations are
      needed to better-define the relation of omentin 1 and insulin resistance in obese
      children. 

PMID- 24085390
TI  - A novel factor, Tmem176b, induced by activin-like kinase 2 signal promotes the
      differentiation of myoblasts into osteoblasts.
AB  - Previous studies have suggested some interactions between muscle tissues and bone
      metabolism. The constitutively activating mutation (R206H) of the BMP type I
      receptor, activin-like-kinase 2 (ALK2), causes fibrodysplasia ossificans
      progressiva (FOP), which is characterized by extensive ossifications within
      muscle tissues. In the present study, we revealed that Tmem176b mRNA levels were
      upregulated by stable transfection of ALK2 (R206H) in mouse myoblastic C2C12
      cells. Transient Tmem176b overexpression elevated levels of osteoblast
      differentiation markers, such as Osterix and alkaline phosphatase, as well as
      mineralization in C2C12 cells. In addition, Tmem176b overexpression elevated the
      levels of these markers in mouse osteoblastic MC3T3-E1 cells. On the other hand,
      Tmem176b overexpression suppressed the levels of myogenic markers, such as MyoD
      and myogenin in C2C12 cells, although it did not affect the levels of
      chondrogenic markers, such as type II and X collagens. In conclusion, the present
      study is the first to demonstrate that Tmem176b induces the differentiation of
      myoblasts into an osteoblast lineage. 

PMID- 24085391
TI  - Comparative metagenomic analysis of bacterial populations in three full-scale
      mesophilic anaerobic manure digesters.
AB  - While the use of anaerobic digestion to generate methane as a source of bioenergy
      is increasing worldwide, our knowledge of the microbial communities that perform
      biomethanation is very limited. Using next-generation sequencing, bacterial
      population profiles were determined in three full-scale mesophilic anaerobic
      digesters operated on dairy farms in the state of Vermont (USA). To our
      knowledge, this is the first report of a metagenomic analysis on the bacterial
      population of anaerobic digesters using dairy manure as their main substrate. A
      total of 20,366 non-chimeric sequence reads, covering the V1-V2 hypervariable
      regions of the bacterial 16S rRNA gene, were assigned to 2,176 operational
      taxonomic units (OTUs) at a genetic distance cutoff value of 5 %. Based on their
      limited sequence identity to validly characterized species, the majority of OTUs
      identified in our study likely represented novel bacterial species. Using a naive
      Bayesian classifier, 1,624 anaerobic digester OTUs could be assigned to 16
      bacterial phyla, while 552 OTUs could not be classified and may belong to novel
      bacterial taxonomic groups that have yet to be described. Firmicutes,
      Bacteroidetes, and Chloroflexi were the most highly represented bacteria overall,
      with Bacteroidetes and Chloroflexi showing the least and the most variation in
      abundance between digesters, respectively. All digesters shared 132 OTUs, which
      as a "core" group represented 65.4 to 70.6 % of sequences in individual
      digesters. Our results show that bacterial populations from microbial communities
      of anaerobic manure digesters can display high levels of diversity despite
      sharing a common core substrate.

PMID- 24085392
TI  - Cloning and enzymatic characterization of four thermostable fungal endo-1,4-beta
      xylanases.
AB  - Endo-1,4-beta-xylanases (EC 3.2.1.8) hydrolyze the 1,4-beta-D-xylosidic linkages
      in xylans, the most abundant hemicellulose in plant cell walls. Xylanase enzymes
      have numerous industrial applications, including the manufacturing of animal
      feed, bread, juice and wine, pulp and paper, and biofuels. In this study, two
      glycosyl hydrolase family 10 members designated GtXyn10A and GtXyn10B and two
      glycosyl hydrolase family 11 members, OpXyn11A and CcXyn11C, were functionally
      expressed and subjected to biochemical characterization. The K(M), V(max), and
      k(cat) values of the four xylanases, determined using birchwood xylan, ranged
      from 0.27 to 1.1 mg/mL, 130 to 980 MUmol/min/mg, and 109 to 344 s-1,
      respectively, where OpXyn11A gave the highest and GtXyn10B the lowest values for
      all three parameters. Substrate specificity studies and analysis of the products
      released during the degradation of xylo-oligosaccharides and three types of xylan
      revealed significant differences in catalytic properties, particularly between
      OpXyn11A and the other xylanases and between the family 10 and the family 11
      xylanases. Molecular modeling suggests that the unique substrate specificity of
      OpXyn11A can be attributed to the presence of a serine rather that an asparagine
      or aspartate residue at the +1 substrate binding site. Additionally, all four
      xylanases exhibited biochemical characteristics of interest for various
      commercial applications.

PMID- 24085393
TI  - The highly modified microcin peptide plantazolicin is associated with nematicidal
      activity of Bacillus amyloliquefaciens FZB42.
AB  - Bacillus amyloliquefaciens FZB42 has been shown to stimulate plant growth and to
      suppress the growth of plant pathogenic organisms including nematodes. However,
      the mechanism underlying its effect against nematodes remains unknown. In this
      study, we screened a random mutant library of B. amyloliquefaciens FZB42
      generated by the mariner transposon TnYLB-1 and identified a mutant strain F5
      with attenuated nematicidal activity. Reversible polymerase chain reaction
      revealed that three candidate genes RAMB_007470, yhdY, and prkA that were
      disrupted by the transposon in strain F5 potentially contributed to its decreased
      nematicidal activity. Bioassay of mutants impaired in the three candidate genes
      demonstrated that directed deletion of gene RBAM_007470 resulted in loss of
      nematicidal activity comparable with that of the F5 triple mutant. RBAM_007470
      has been reported as being involved in biosynthesis of plantazolicin, a
      thiazole/oxazole-modified microcin with hitherto unknown function. Electrospray
      ionization time-of-flight mass spectrometry (ESI-TOF-MS) analyses of surface
      extracts revealed that plantazolicin bearing a molecular weight of 1,354 Da was
      present in wild-type B. amyloliquefaciens FZB42, but absent in the
      DeltaRABM_007470 mutant. Furthermore, bioassay of the organic extract containing
      plantazolicin also showed a moderate nematicidal activity. We conclude that a
      novel gene RBAM_007470 and its related metabolite are involved in the
      antagonistic effect exerted by B. amyloliquefaciens FZB42 against nematodes.

PMID- 24085394
TI  - Basic studies on the role of components of Bacillus megaterium as flotation
      biocollectors in sulphide mineral separation.
AB  - Studies were carried out to assess the utility of the cellular and extracellular
      constituents of Bacillus megaterium for the flotation of sphalerite and galena
      minerals. Based on the flotation results on the individual minerals, it was
      observed that sphalerite was preferentially floated compared to galena. A maximum
      selectivity index (SI) value of 11.7 was achieved in the presence of the soluble
      fraction of the thermolysed cells, which was higher than that obtained with the
      intact cells (SI of 6.5) and the insoluble fraction of the thermolysed cells (SI
      of 9.6). The results of the various enzymatic treatment tests revealed that
      extracellular DNA played a vital role in the selective flotation of sphalerite. A
      noteworthy finding was that the single-stranded DNA (ssDNA) had a higher
      biocollector capacity vis-a-vis the double-stranded DNA (dsDNA), leading to
      better flotation efficiency. About 95 % recovery of sphalerite could be achieved
      from the mineral mixture by the combined addition of the ssDNA with the non-DNA
      components of the bacterial cells, resulting in a maximum SI of 19.1. Calcium and
      phosphate components of the nutrient media were found to be essential for better
      selectivity of separation of sphalerite. The mechanisms of microbe-mineral
      interaction are discussed.

PMID- 24085395
TI  - Virus-like particles produced in Saccharomyces cerevisiae elicit protective
      immunity against Coxsackievirus A16 in mice.
AB  - Hand, foot, and mouth disease (HFMD) has caused significant morbidity and
      mortality in the Asia-Pacific regions, particularly in infants and young
      children. Coxsackievirus A16 (CA16) represents one of the major causative agents
      for HFMD, and the development of a safe and effective vaccine preventing CA16
      infections has become a public health priority. In this study, we have developed
      a yeast system for the production of virus-like particles (VLPs) for CA16 by co
      expressing P1 and 3CD of CA16 in Saccharomyces cerevisiae. These VLPs exhibit
      similarity in both protein composition and morphology as empty particles from
      CA16-infected cells. Immunization with CA16 VLPs in mice potently induced CA16
      specific IgG and neutralization antibodies in a dose-dependent manner. IgG
      subclass isotyping revealed that IgG1 and lgG2b were dominantly induced by VLPs.
      Meanwhile, cytokine profiling demonstrated that immunization with VLPs
      significantly induced the secretion of IFN-gamma, indicating potent cellular
      immune response. Furthermore, in vivo challenge experiments showed that passive
      immunization with anti-VLPs sera conferred full protection against lethal CA16
      challenge in neonate mice. Taken together, our data demonstrated that VLPs
      produced in yeast might have the potential to be further developed as a vaccine
      candidate against HFMD. 

PMID- 24085396
TI  - Successful operation of continuous reactors at short retention times results in
      high-density, fast-rate Dehalococcoides dechlorinating cultures.
AB  - The discovery of Dehalococcoides mccartyi reducing perchloroethene and
      trichloroethene (TCE) to ethene was a key landmark for bioremediation
      applications at contaminated sites. D. mccartyi-containing cultures are typically
      grown in batch-fed reactors. On the other hand, continuous cultivation of these
      microorganisms has been described only at long hydraulic retention times (HRTs).
      We report the cultivation of a representative D. mccartyi-containing culture in
      continuous stirred-tank reactors (CSTRs) at a short, 3-d HRT, using TCE as the
      electron acceptor. We successfully operated 3-d HRT CSTRs for up to 120 days and
      observed sustained dechlorination of TCE at influent concentrations of 1 and 2 mM
      TCE to >= 97 % ethene, coupled to the production of 10(12) D. mccartyi cells
      Lculture (-1). These outcomes were possible in part by using a medium with low
      bicarbonate concentrations (5 mM) to minimize the excessive proliferation of
      microorganisms that use bicarbonate as an electron acceptor and compete with D.
      mccartyi for H2. The maximum conversion rates for the CSTR-produced culture were
      0.13 +/- 0.016, 0.06 +/- 0.018, and 0.02 +/- 0.007 mmol Cl(-) Lculture (-1) h(
      1), respectively, for TCE, cis-dichloroethene, and vinyl chloride. The CSTR
      operation described here provides the fastest laboratory cultivation rate of high
      cell density Dehalococcoides cultures reported in the literature to date. This
      cultivation method provides a fundamental scientific platform for potential
      future operations of such a system at larger scales.

PMID- 24085397
TI  - Mating type genes and cryptic sexuality as tools for genetically manipulating
      industrial molds.
AB  - A large number of molds serve as producer strains for the industrial production
      of pharmaceuticals, foods, or organic chemicals. To optimize strains for
      production processes, conventional strain development programs use random
      mutagenesis and, more recently, recombinant technologies to generate microbial
      strains with novel and advantageous properties. The recent detection of mating
      type genes in fungal production strains and the discovery of cryptic sexuality in
      presumably asexual fungi open up novel strategies for generating progeny with
      new, as yet unobserved properties. Mating type genes, which can be considered as
      "sex genes," not only direct sexual development but also regulate a broad range
      of fungal secondary metabolites. In addition, they control hyphal morphology,
      which has a direct impact on production processes that are often conducted in
      huge fermenter tanks. Here, we survey the occurrence and function of mating type
      genes that have been discovered in a wide range of industrial fungal producer
      strains. The possibility to obtain progeny from industrial producers by sexual
      mating provides an exciting alternative to conventional strain improvement
      programs aiming to generate optimized recombinant production strains. 

PMID- 24085399
TI  - Agreement between virtual and in-the-field environmental audits of assisted
      living sites.
AB  - The authors investigated the use of Google Earth's Street View option to audit
      the presence of built environment features that support older adults' walking.
      Two raters conducted virtual (Street View) and in-the-field audits of 48 street
      segments surrounding urban and suburban assisted living sites in metropolitan
      Vancouver, BC, Canada. The authors determined agreement using absolute agreement.
      Their findings indicate that Street View may identify the presence of features
      that promote older adults' walking, including sidewalks, benches, public
      washrooms, and destinations. However, Street View may not be as reliable as in
      the-field audits to identify details associated with certain items, such as
      counts of trees or street lights; presence, features, and height of curb cuts;
      and sidewalk continuity, condition, and slope. Thus, the appropriateness of
      virtual audits to identify microscale built environment features associated with
      older adults' walking largely depends on the purpose of the audits-specifically,
      whether the measurer seeks to capture highly detailed features of the built
      environment.

PMID- 24085400
TI  - Prevalence and clinical correlates of sarcopenia in community-dwelling older
      people: application of the EWGSOP definition and diagnostic algorithm.
AB  - BACKGROUND: Muscle impairment is a common condition in older people and a
      powerful risk factor for disability and mortality. The aim of this study was to
      apply the European Working Group on Sarcopenia in Older People criteria to
      estimate the prevalence and investigate the clinical correlates of sarcopenia, in
      a sample of Italian community-dwelling older people. METHODS: Cross-sectional
      analysis of 730 participants (74% aged 65 years and older) enrolled in the
      InCHIANTI study. Sarcopenia was defined according to the European Working Group
      on Sarcopenia in Older People criteria using bioimpedance analysis for muscle
      mass assessment. Logistic regression analysis was used to identify the factors
      independently associated with sarcopenia. RESULTS: Sarcopenia defined by the
      European Working Group on Sarcopenia in Older People criteria increased steeply
      with age (p < .001), with 31.6% of women and 17.4% of men aged 80 years or older
      being affected by this condition. Higher education (odds ratio: 0.85; 95% CI:
      0.74-0.98), lower insulin-like growth factor I (lowest vs highest tertile, odds
      ratio: 3.89; 95% CI: 1.03-14.1), and low bioavailable testosterone (odds ratio:
      2.67; 95% CI: 1.31-5.44) were independently associated with the likelihood of
      being sarcopenic. Nutritional intake, physical activity, and level of comorbidity
      were not associated with sarcopenia. CONCLUSIONS: Sarcopenia identified by the
      European Working Group on Sarcopenia in Older People criteria is a relatively
      common condition in Italian octogenarians, and its prevalence increases with
      aging. Correlates of sarcopenia identified in this study might suggest new
      approaches for prevention and treatment of sarcopenia.

PMID- 24085402
TI  - NSC126188 induces apoptosis of prostate cancer PC-3 cells through inhibition of
      Akt membrane translocation, FoxO3a activation, and RhoB transcription.
AB  - We previously reported that NSC126188 caused apoptosis of cancer cells by
      inducing expression of RhoB. We here present that NSC126188 induces apoptosis of
      prostate cancer PC-3 cells by inhibiting Akt/FoxO3 signaling, which mediates RhoB
      upregulation. The apoptosis and Akt dephosphorylation caused by NSC126188 was not
      substantially relieved by overexpressing wild-type Akt but was relieved by
      overexpressing constitutively active Akt (CA-Akt) or myristoylated Akt (myr-Akt).
      Furthermore, overexpression of CA-Akt or myr-Akt downregulated RhoB expression,
      indicating that RhoB expression is regulated by Akt signaling. Interestingly,
      membrane translocation of GFP-Akt by insulin exposure was abolished in the cells
      pretreated with NSC126188 suggesting that NSC126188 directly interfered with
      translocation of Akt to the plasma membrane. In addition, NSC126188 activated
      FoxO3a by dephosphorylating S253 via Akt inhibition. Activated FoxO3a
      translocated to the nucleus and increased transcription of RhoB and other target
      genes. PC-3 cells transiently overexpressing FoxO3a exhibited increased RhoB
      expression and apoptosis in response to NSC126188. Conversely, FoxO3a knockdown
      reduced NSC126188-induced RhoB expression and cell death. These results suggest
      that RhoB may be a target gene of FoxO3a and is regulated by Akt signaling. Taken
      together, NSC126188 induces apoptosis of PC-3 cells by interfering with membrane
      recruitment of Akt, resulting in Akt dephosphorylation and FoxO3a activation,
      which leads to transcription of RhoB. 

PMID- 24085401
TI  - Branched chain amino acids are associated with muscle mass in functionally
      limited older adults.
AB  - BACKGROUND: Metabolic profiling may provide insight into biologic mechanisms
      related to the maintenance of muscle and fat-free mass in functionally limited
      older adults. The objectives of the study were to characterize the association
      between thigh muscle cross-sectional area (CSA) and the fat-free mass index
      (FFMI; total lean mass/height(2)) with the serum metabolite profile, to further
      identify significant metabolites as associated with markers of insulin resistance
      or inflammation, and to develop a metabolite predictor set representative of
      muscle CSA and the FFMI in functionally limited older adults. METHODS:
      Multivariable-adjusted linear regression was used on mass spectrometry-based
      metabolomic data to determine significant associations between serum metabolites
      with muscle CSA and the FFMI in 73 functionally limited (Short Physical
      Performance Battery <= 10) older adults (age range: 70-85 years). Significant
      metabolites were further examined for associations with markers of insulin
      resistance (homeostasis model assessment of insulin resistance) or inflammation
      (tumor necrosis factor-alpha and interleukin-6). Multivariable-adjusted stepwise
      regression was used to develop a metabolite predictor set representative of
      muscle CSA and the FFMI. RESULTS: Seven branched chain amino acid-related
      metabolites were found to be associated with both muscle CSA and the FFMI.
      Separately, two metabolites were identified as insulin resistance-associated
      markers of the FFMI, whereas four metabolites were identified as inflammation
      associated markers of either muscle CSA or the FFMI. Stepwise models identified
      combinations of metabolites to explain approximately 68% of the variability
      inherent in muscle CSA or the FFMI. CONCLUSIONS: Collectively, we report multiple
      branched chain amino acids and novel inflammation-associated tryptophan
      metabolites as markers of muscle CSA or the FFMI in functionally limited older
      adults.

PMID- 24085404
TI  - Technical note: Nitrogen isotopic fractionation can be used to predict nitrogen
      use efficiency in dairy cows fed temperate pasture.
AB  - The objective of this study was to investigate the relationship between nitrogen
      isotopic fractionation (delta(15)N) and nitrogen-use efficiency (milk
      nitrogen/nitrogen intake; NUE) in pasture-fed dairy cows supplemented with
      increasing levels of urea to mimic high rumen degradable protein pastures in
      spring. Fifteen cows were randomly assigned to freshly cut pasture and either
      supplemented with 0, 250, or 336 g urea/d. Feed, milk, and plasma were analyzed
      for delta(15)N, milk and plasma for urea nitrogen concentration, and plasma for
      ammonia concentration. Treatment effects were tested using ANOVA and
      relationships between variables were established by linear regression. Lower dry
      matter intake (P = 0.002) and milk yield (P = 0.002) occurred with the highest
      urea supplementation (336 g urea/d) compared with the other two treatments. There
      was a strong linear relationship between milk delta(15)N - feed delta(15)N and
      NUE: [NUE (%) = 58.9 - 10.17 * milk delta(15)N - feed delta(15)N (0/00) (r(2) =
      0.83, P < 0.001, SE = 1.67)] and between plasma delta(15)N - feed delta(15)N and
      NUE: [NUE (%) = 52.4 - 8.61 * plasma delta(15)N - feed delta(15)N (0/00) (r(2) =
      0.85, P < 0.001, SE = 1.56)] . This study confirmed the potential use of
      delta(15)N to predict NUE in cows consuming different levels of rumen degradable
      protein. 

PMID- 24085405
TI  - Intrauterine growth restricted piglets defined by their head shape ingest
      insufficient amounts of colostrum.
AB  - The increasing litter sizes of modern pig breeds have led to a significant number
      of piglets that are born undersized ("small" piglets) and some have been exposed
      to different degrees of intrauterine growth restriction (IUGR). The aim of this
      study was to investigate the physiology and capability to ingest colostrum of
      these small piglets, suffering from various degrees of IUGR, to see if their IUGR
      score could be a useful tool for easy identification of piglets in need of
      intervention in the colostrum period. Piglets were classified at birth based on
      head morphology. Piglets were classified either "normal," "mildly IUGR" (m-IUGR),
      or "severe IUGR" (s-IUGR), based on head morphology. Blood samples were collected
      at birth and at 24 h, and colostrum intake during two 12-h periods and blood
      metabolites at 0 and 24 h were measured. At 24 h, piglets weighing <900 g at
      birth and the median piglet in birth order were sacrificed, and organ weights and
      hepatic glycogen were measured. Overall, there was an influence of the piglets'
      classification on most characteristics, with normal piglets having a greater
      colostrum intake between 0 and 12 h (P < 0.001) and between 12 and 24 h (P <
      0.05), and higher birth weight, crown rump length, body mass index, and ponderal
      index (P < 0.001), and a tendency toward a higher vitality score (P < 0.069) than
      s-IUGR piglets. There was a time * IUGR interaction, with plasma glucose levels
      being lowered (P < 0.001) and lactate levels elevated (P < 0.001) in s-IUGR
      piglets at 24 h compared with normal and m-IUGR piglets. Some differences were
      found in electrolytes; sodium plasma concentrations were greatest for normal
      piglets (P < 0.05) and highest at 0 h (P < 0.05). At 24 h of age, s-IUGR piglets
      had a higher heart (P < 0.001) and brain percentage (P < 0.001), and a lower
      liver percentage (P < 0.001) relative to body weight, compared with normal
      piglets. In addition, s-IUGR piglets had less hepatic glycogen than m-IUGR
      piglets and normal piglets. The present study showed that the physiology of
      piglets in the colostrum period was affected by IUGR status at birth and their
      intermediary metabolism was altered due to different colostrum intakes.
      Furthermore, it was demonstrated that the head shape of newborn piglets is a good
      selection criteria for identifying piglets that need oral supplementation during
      the neonatal stage. 

PMID- 24085406
TI  - Empirical growth curve estimation considering multiple seasonal compensatory
      growths of body weights in Japanese Thoroughbred colts and fillies.
AB  - Thoroughbred horses are seasonal mating animals, and their foals are born yearly
      in spring seasons. In northern regions or countries, the foals generally show a
      typical seasonal compensatory growth pattern, where their growth rate declines in
      winter and increases in the next spring. In this study, a new empirical approach
      is proposed to adjust for this compensatory growth when growth curve equations
      are estimated, by using BW of Japanese Thoroughbred colts and fillies raised in
      Hidaka, Hokkaido. Based on the traditional Richards growth curve equation, new
      growth curve equations were developed and fit to the weight-age data. The foals
      generally experience 2 major winter seasons before their debut in horseracing.
      The new equations had sigmoid subfunctions that can empirically adjust the first
      and second year compensatory growths, combined with the Richards biological
      parameter responsible for the maturity of animals. The unknown parameters
      included in the equations were estimated by SAS NLMIXED procedure. The goodness
      of-fit was examined by using several indices of goodness-of-fit (i.e., Akaike's
      information criterion, Bayesian information criterion, -2 log likelihood, and
      residual sum of squares) for the multiple applications of the subfunctions. The
      indices indicated the best fit of the new equations including both subfunctions
      for the first and second compensatory growths to the weight-age data. The shapes
      of the growth curves were improved during the periods of compensatory growth. The
      proposed method is one of the useful approaches for adjusting multiple seasonal
      compensatory growths in growth curve estimations of Thoroughbreds and for the
      management of young horses during the compensatory periods. 

PMID- 24085407
TI  - Genetic parameters for calving and conformation traits in Charolais x Montbeliard
      and Charolais x Holstein crossbred calves.
AB  - Charolais sires can be mated to Montbeliard or Holstein dairy cows to produce
      crossbred calves sold for meat production. Heritabilities and correlations
      between traits can differ when they are calculated within Charolais * Montbeliard
      or within Charolais * Holstein population. Moreover, the genetic correlation
      between the same trait measured on Charolais * Montbeliard and on Charolais *
      Holstein crossbred calves is not necessarily unity. The first objective of this
      study was to estimate heritability and genetic correlation between traits within
      Charolais * Montbeliard and within Charolais * Holstein population. The second
      objective was to investigate if those traits are genetically identical between
      crossbred populations. Traits studied were calving difficulty, birth weight,
      height, bone thinness, and muscular development. Data included 22,852 Charolais *
      Montbeliard and 16,012 Charolais * Holstein crossbred calves from 391 Charolais
      sires. Heritabilities estimated separately within each crossbred population were
      similar. Stronger genetic correlations were observed in Charolais * Holstein
      population compared with Charolais * Montbeliard between calving difficulty and
      height (0.67 vs. 0.54), calving difficulty and bone thinness (0.42 vs. 0.27),
      birth weight and bone thinness (0.52 vs. 0.20), and birth weight and muscular
      development (0.41 vs. 0.18). Bivariate analysis considering observations on
      Charolais * Montbeliard and on Charolais * Holstein as different traits showed
      that genetic variances and heritabilities were similar for all traits except
      height. Birth weight and muscular development were genetically identical traits
      in each crossbred populations, with genetic correlations of 0.96 and 0.99.
      Genetic correlations were 0.91 for calving difficulty, 0.80 for height, and 0.70
      for bone thinness and log-likelihood ratio tests indicated that they were
      significantly different from 1 (P <= 0.01). Results show evidence for reranking
      of Charolais sires for calving difficulty, height, and bone thinness depending on
      whether they are mated to Montbeliard or Holstein cows. 

PMID- 24085408
TI  - Metabolizable protein supply modulated the acute-phase response following
      vaccination of beef steers.
AB  - Our objective was to evaluate the effects of MP supply, through RUP
      supplementation, on the acute-phase response of beef steers following
      vaccination. On d 0, Brangus-crossbred steers (n = 24; 173 +/- 31 kg; 175 +/- 16
      d of age) were randomly assigned to receive 1 of 3 isocaloric diets formulated to
      provide 85, 100, and 115% of the daily MP requirements of a beef steer gaining
      0.66 kg of BW daily. Diets were limit-fed at 1.8% of BW (DM basis) and
      individually provided to steers once daily (0800 h) from d 0 to 29. Steers were
      weighed on d 0 and 29, following a 12-h period of feed and water withdrawal. On d
      7, steers were vaccinated against Mannheimia haemolytica (OneShot, Pfizer), and
      blood samples were collected on d 0, 7, 8, 10, 14, 21, and 30. Plasma metabolites
      were analyzed as repeated measures using the MIXED procedure of SAS. Final BW and
      ADG were similar (P >= 0.50) among treatments (mean = 184 +/- 9 kg and 0.5 +/-
      0.08 kg/d, respectively). Effects of time were detected (P < 0.01) for plasma
      concentrations of all acute-phase proteins, which peaked between d 7 to 14,
      returning to baseline concentrations by d 29. Treatment effects were not detected
      (P >= 0.19) for plasma concentrations of acid-soluble protein, albumin,
      fibrinogen, IGF-1 and serum amyloid-A. Plasma concentrations of total protein
      (TP) and plasma urea nitrogen (PUN) increased (P <= 0.05) with increasing supply
      of MP (87.1, 89.6, and 90.1 +/- 1.09 mg TP/mL and 6.1, 8.3, and 10.3 +/- 0.41 mg
      PUN/dL for 85, 100, and 115% MP steers, respectively). From d 10 to 29, steers
      provided 115% MP had less (P < 0.001) plasma concentrations of ceruloplasmin than
      steers fed 85 and 100% MP, which had similar plasma ceruloplasmin concentrations.
      On d 14, plasma concentrations of haptoglobin were greatest (P <= 0.06) for
      steers fed 115% MP, intermediate for 100% MP, and least for 85% MP (0.98, 0.71
      and 0.44 +/- 0.099 mg/mL, respectively). On d 10, plasma concentrations of
      creatinine were greater (P = 0.01) for steers fed 115 vs. 85% MP, and
      intermediate for steers fed 100% MP (1.63, 1.28, and 1.50 +/- 0.099 mg/dL,
      respectively). Thus, steers provided increasing metabolizable protein had greater
      plasma concentrations of haptoglobin, creatinine, total protein and PUN following
      vaccination against M. haemolytica. 

PMID- 24085409
TI  - An examination of the association of serum IGF-I concentration, potential
      candidate genes, and fiber type composition with variation in residual feed
      intake in progeny of Red Angus sires divergent for maintenance energy EPD.
AB  - Investigating the genetic and physiological drivers of postweaning residual feed
      intake (RFI) and finishing phase feed efficiency (FE) may identify underlying
      mechanisms that are responsible for the variation in these complex FE traits. The
      objectives were 1) to evaluate the relationship of serum IGF-I concentration and
      muscle gene expression with postweaning RFI and sire maintenance energy (MEM) EPD
      and 2) to determine fiber type composition as it relates to postweaning RFI and
      finishing phase FE. Results indicate that RFI and serum IGF-I concentration were
      not associated (P > 0.05); however, negative correlations (P < 0.05) between sire
      MEM EPD and serum IGF-I concentration were observed. Gene expression differences
      between high- and low-RFI animals were observed in cohort 1, where IGFBP5
      expression was greater (P < 0.05) in high-RFI animals. When animals were grouped
      according to sire MEM EPD, the low MEM EPD group of cohort 1 showed greater
      muscle mRNA expression (P < 0.01) of fatty acid synthase (FASN) and marginally (P
      < 0.10) greater expression of IGFBP5 and C/EBP alpha (C/EBPalpha) whereas the
      high MEM EPD group of cohort 2 had greater muscle mRNA expression of IGFBP2 (P <
      0.05) and C/EBPalpha (P <= 0.01) and marginally (P < 0.10) greater expression of
      IGFBP3. Biopsy tissue samples collected at harvest revealed that the percentage
      of type IIa fibers was lower (P <= 0.05) in high-RFI steers, with a similar trend
      (P < 0.10) being observed in high finishing phase FE steers. The percentage of
      type IIb fibers was higher (P < 0.05) in high-RFI (and finishing phase FE) steers
      than in low-RFI (and finishing phase FE) steers. There was a marginal, negative
      correlation between RFI and type I (r = -0.36, P = 0.08) and IIa (r = -0.37, P =
      0.07) fiber percentages and a positive correlation (r = 0.48, P = 0.01) between
      RFI and type IIb fiber percentage whereas finishing phase FE was negatively
      correlated (r = -0.43, P = 0.03) with type I fiber percentage and positively
      correlated (r = 0.44, P = 0.03) with type IIb fiber percentage. Therefore, our
      data indicate that 1) serum IGF-I (collected at weaning) is not an indicator of
      postweaning RFI, 2) the GH-IGF axis appears to have some involvement with RFI at
      the molecular level; however, muscle gene expression results were not consistent
      across cohorts, and 3) low-RFI animals may have the ability to more efficiently
      maintain and accrete muscle mass due to their fiber type composition,
      specifically a greater proportion of type I fibers. 

PMID- 24085410
TI  - Amino acid and phosphorus digestibility and concentration of digestible and
      metabolizable energy in hydrolyzed feather meal fed to growing pigs.
AB  - Two experiments were conducted to determine the standardized ileal digestibility
      (SID) of AA (Exp. 1), the standardized total tract digestibility (STTD) of P, and
      the concentration of DE and ME (Exp. 2) in hydrolyzed feather meal (FM) fed to
      growing pigs. Eight samples of FM were obtained from 4 different processing
      plants (FM1, FM2, FM3, and FM4). Each plant provided samples of FM without and
      with added blood. In Exp. 1, 10 barrows (initial BW: 24.0 +/- 0.8 kg) were
      prepared with a T-cannula in the distal ileum and allotted to a 10 * 10 Latin
      square design with 10 diets and ten 7-d periods. A N-free diet, a diet based on
      soybean meal (SBM), and 8 diets based on a combination of SBM and each of the 8
      sources of FM were formulated. Values for the SID of CP and AA in each source of
      FM were calculated using the difference procedure. The SID of CP and all AA was
      different (P < 0.001) among sources of FM. Among the indispensable AA, the
      overall effect of addition of blood was statistically significant (P < 0.05) for
      the SID of Ile, Leu, Lys, Phe, and Val, but for some sources, the SID of these AA
      was increased by addition of blood, whereas for other sources, the SID was
      reduced or not changed (interaction, P < 0.05). As an example, the SID of Lys in
      FM3 and FM4 with added blood were greater (P < 0.05) than in FM3 and FM4 without
      blood, but no difference in the SID of Lys was observed for FM1 and FM2 without
      and with blood (interaction, P < 0.01). In Exp. 2, 72 growing barrows (initial
      BW: 13.3 +/- 1.5 kg) were used with 9 diets and 8 replicate pigs per diet. A corn
      diet consisting of 98.4% corn was formulated and 8 additional diets were
      formulated by mixing corn with 25% FM. The STTD of P and the DE and ME of each
      source of FM were calculated using the difference procedure. The STTD of P tended
      (P = 0.09) to be different among FM sources and the STTD of P in FM with added
      blood was less than in FM without blood. On a DM basis, DE and ME values were
      affected (P < 0.05) by both source of FM and addition of blood. However, an
      interaction (P < 0.05) between source of FM and addition of blood for ME was
      observed because addition of blood to FM3 and FM4 reduced (P < 0.05) the ME,
      whereas addition of blood to FM1 and FM2 had no impact on ME. In summary, the SID
      of AA, STTD of P, and the energy concentration vary among sources of FM and the
      effects of adding blood to FM is not consistent among sources. 

PMID- 24085411
TI  - In memoriam: Douglas Emerson Hogue.

PMID- 24085412
TI  - Wolf presence in the ranch of origin: impacts on temperament and physiological
      responses of beef cattle following a simulated wolf encounter.
AB  - This experiment evaluated temperament, vaginal temperature, and plasma cortisol
      in beef cows from wolf-naive and wolf-experienced origins that were subjected to
      a simulated wolf encounter. Multiparous, pregnant, nonlactating Angus-crossbreed
      cows from the Eastern Oregon Agricultural Research Center located near Burns, OR
      (CON; n = 50), and from a commercial operation near Council, ID (WLF; n = 50),
      were used. To date, grey wolves are not present around Burns, OR, and thus CON
      were naive to wolves. Conversely, wolves are present around Council, ID, and WLF
      cows were selected from a herd that had experienced multiple confirmed wolf
      predation episodes from 2008 to 2012. Following a 50-d commingling and adaptation
      period, CON and WLF cows were ranked by temperament, BW, and BCS and allocated to
      5 groups (d 0; 10 CON and 10 WLF cows/group). Groups were individually subjected
      to the experimental procedures on d 2 (n = 3) and d 3 (n = 2). Before the
      simulated wolf encounter, cow temperament was assessed and blood samples and
      vaginal temperatures (using intravaginal data loggers) were collected
      (presimulation assessments). Cows were then sorted by origin, moved to 2 adjacent
      drylot pens (10 WLF and 10 CON cows/pen), and subjected to a simulated wolf
      encounter event for 20 min, which consisted of 1) cotton plugs saturated with
      wolf urine attached to the drylot fence, 2) continuous reproduction of wolf
      howls, and 3) 3 leashed dogs that were walked along the fence perimeter.
      Thereafter, WLF and CON cows were commingled and returned to the handling
      facility for postsimulation assessments, which were conducted immediately after
      exposure to wolf-urine-saturated cotton plugs, wolf howl reproduction, and 20-s
      exposure to the 3 dogs while being restrained in a squeeze chute. Chute score,
      temperament score, and plasma cortisol concentration increased (P <= 0.01) from
      pre- to postsimulation assessment in WLF but did not change in CON cows (P >=
      0.19). Exit velocity decreased (P = 0.01) from pre- to postsimulation assessment
      in CON but did not change (P = 0.79) in WLF cows. In addition, WLF cows had a
      greater (P = 0.03) increase in temperature from pre- to postsimulation
      assessments compared with CON cows. In conclusion, the simulated wolf encounter
      increased excitability and fear-related physiological stress responses in cows
      that originated from a wolf-experienced herd but not in cows that originated from
      a wolf-naive herd. 

PMID- 24085413
TI  - Growth promoting technologies reduce greenhouse gas, alcohol, and ammonia
      emissions from feedlot cattle.
AB  - Increased animal productivity has the potential to reduce the environmental
      impact per unit of consumable product and is believed to be the most promising
      and sustainable mitigation technique to meet increasing demand for high quality
      protein. The feedlot industry uses ionophores, antibiotics, growth implants, and
      beta2-adrenergic agonists to improve health and growth performance of cattle.
      These technologies not only increase productivity but also alter microbes in the
      rumen and increase nitrogen retention in the animal, which may lead to changes in
      greenhouse gas (GHG), volatile organic compound (VOC), and ammonia (NH3)
      emissions from feedlot cattle. The present study investigated GHG, VOC, and NH3
      emissions from 160 Angus crossbred steers. Steers were blocked by weight in a
      randomized block design and assigned to 16 pens of 10 animals each. Treatments
      applied were 1) control (CON; no technology application), 2) monensin and tylosin
      phosphate (MON), 3) monensin, tylosin phosphate, and growth implant (IMP), and 4)
      monensin, tylosin phosphate, growth implant, and zilpaterol hydrochloride (fed
      during the last 20 d of the feeding period; BAA). Cattle were on feed for an
      average of 107 d. Performance variables (DMI, BW, ADG, and G:F) and carcass
      traits (HCW, dressing percent, KPH, LM area, fat thickness, marbling score, yield
      grade, and quality grade) were measured. Gaseous emissions were measured during
      the last 10 d of the feeding period when animals were housed in 4 totally
      enclosed identical cattle pen enclosures. To quantify gaseous emissions a 4*4
      Latin square design (n=4) was used. Gaseous emissions were analyzed using Proc
      Mixed in SAS and reported in grams per kilogram HCW per day and grams per
      kilogram per animal per hour. Treatment with IMP and BAA increased (P<0.05) ADG,
      final BW, and HCW. Cattle on BAA had greater HCW and LM area (P<0.05) and had
      lower (P<0.05) CH4, methanol, and NH3 emissions per kilogram HCW than cattle on
      the remaining treatments. Methane emissions were similar for CON and IMP treated
      cattle. Nitrous oxide emissions were similar across CON, MON, and IMP treated
      cattle and were higher in BAA treated cattle (P<0.05). The present study provides
      a better understanding of how application of growth promoting technologies to
      feedlot steers affects GHG, VOC, and NH3 emissions per kilogram of product.

PMID- 24085414
TI  - Effect of selenium concentration on feed preferences by cattle and sheep.
AB  - Selenium-accumulator plants are reputed to be unpalatable to livestock. The
      objective of this study was to determine if sheep and cattle could discriminate
      between forages and feeds with different concentrations of Se. In the first
      study, cattle and sheep preferences for intermediate wheatgrass (Thinopyrum
      intermedium), alfalfa (Medicago sativa), and western aster (Symphyotrichum
      ascendens) of varying Se concentrations were assessed. The Se concentrations
      ranged from 0.8 to 50 mg/kg (DM) in grass, 1.4 to 275 mg/kg in alfalfa, and 4 to
      4,455 mg/kg in aster. Selenium concentration had no influence (P > 0.05) on the
      initial or subsequent preferences of sheep or cattle for grass or alfalfa. Cattle
      developed an aversion to aster after consuming 95% of the plant material during
      the first brief exposure and subsequently refused to eat any aster. Sheep
      consumption of aster was variable, but their preference was not driven by Se
      concentration. In the next study, cattle and sheep were offered pellets at 1.5%
      of BW (as fed) that contained increasing concentrations of Se from aster (control
      and 5, 25, 45, and 110 mg/kg Se). In trial 1, all pellets were offered. In Trials
      2 and 3, all pellets were offered with the exception of the 5 mg/kg Se pellet and
      the 5 and 25 mg/kg Se pellets, respectively. In trial 1, consumption of the
      control pellet by cattle was greater on all days compared with other Se pellets
      (P < 0.001). Cattle ate more (P < 0.001) of the 5 mg/kg Se pellet than the higher
      Se pellets on d 3, 4, and 5. Sheep ate greater amounts of the control and 5 and
      110 mg/kg Se pellets compared with the 25 and 45 mg/kg Se pellets (P < 0.0001) on
      d 1, and sheep consumed primarily the control and 5 mg/kg Se pellets thereafter.
      In trial 2, cattle and sheep consumed more (P < 0.0001) of the control Se pellet
      than the 25, 45, and 110 mg/kg Se pellets. In trial 3, cattle consumption of the
      control and 45 and 110 mg/kg Se pellets differed on d 2 and 3 (P < 0.001), except
      there was no difference (P > 0.95) in cattle consumption of the control and 45
      mg/kg Se pellets on d 1. Sheep consumed primarily the control and 45 mg/kg Se
      pellets. We conclude that high Se concentrations in fresh forages had no effect
      on initial consumption by cattle or sheep. When given Se pellets, initial
      responses were variable, but the results indicate that cattle and sheep adjusted
      their intake over time to avoid excessive intake of Se. 

PMID- 24085415
TI  - Effect of forage and retail packaging types on meat quality of long-term chilled
      lamb loins.
AB  - The objectives of this study were to determine the effects of different forage
      regimes and modified atmosphere packaging (MAP) systems [high oxygen (HiOx-MAP):
      80% O2 and 20% CO2; and CO2-MAP: 20% CO2 and 80% N2] on color and lipid oxidation
      stability and sensory attributes of long-term chilled lamb loins during retail
      display. Lambs (n = 124) were randomly assigned to several pasture-feeding
      regimes for 12 wk before slaughter. Some had ryegrass (n = 18), lucerne (n = 18),
      chicory (n = 19), plantain (n = 16), or red clover (Clover 12; n = 17) for all 12
      wk. Some were assigned a regime of red clover for 11 wk and pasture for 1 wk
      (Clover 11; n = 18), with others on red clover for 9 wk and pasture for 3 wk
      (Clover 9; n = 18). After the lambs were slaughtered, the paired loins (M.
      longissimus dorsi) were excised at 24 h postmortem, vacuum-packed and stored at 
      1.5  degrees C for 9 wk. Cuts were then made from each loin and randomly
      allocated to either HiOx-MAP or CO2-MAP, and displayed for 7 d at 4  degrees C
      under light. Chemical attributes including lipid oxidation, surface color
      reversing ability, oxygen consumption, and meat quality attributes (color
      stability and sensory characteristics) were determined. Among the different
      forage types, the loins from lambs finished on ryegrass appeared to have greater
      color stability and less lipid oxidation than the loins from lambs finished on
      other forage types (P < 0.05). On the other hand, the loins from lambs finished
      on lucerne had the least color and lipid oxidation stabilities and least color
      reversing ability (P < 0.05). The loins from lambs finished on chicory had higher
      aroma and flavor scores than other pasture types in general (P < 0.05). HiOx-MAP
      negatively influenced meat quality attributes of lamb loins during display, as
      substantial increases in surface discoloration and lipid oxidation were observed,
      along with significant decreases in aroma and flavor during retail display
      compared with the loins in CO2-MAP. These results suggest that different forage
      types and packaging conditions could result in substantial impacts on meat
      quality attributes of long-term chilled lamb loins by affecting oxidation
      stability. Furthermore, the present study suggests that CO2-MAP could provide
      beneficial effects on the eating quality of long-term chilled lamb loins by
      suppressing oxidation-related defects during display without compromising the
      ability of blooming for meat display.

PMID- 24085416
TI  - Effects of immunization against androstenedione or bone morphogenetic protein 15
      (BMP15) on reproductive performance in sheep.
AB  - Partial neutralization of bone morphogenetic protein 15 (BMP15) bioactivity by
      immunization is known to increase ovulation rate in sheep. However, it remains
      uncertain whether BMP15 vaccination would be a suitable procedure for increasing
      lambing rate. The aim of this study was to compare the efficacy of a BMP15
      vaccination treatment on lamb production to that of commercially-available
      androstenedione-based vaccines that are used for this purpose. Ewes were
      immunized for 3 yr against androstenedione, BMP15, or no antigen (control).
      Vaccination with androstenedione or BMP15 altered (P < 0.05) ovulation rate as
      well as litter size at midpregnancy, birth, and weaning compared with controls.
      No differences were detected in the proportions of ewes conceiving in the first
      cycle or partial failure of multiple ovulations. Both gender and litter size
      affected birth weight of the lamb (P < 0.05), but no effect of treatment was
      found. Growth rate was significantly affected (P < 0.05) by gender, birth weight,
      and the number of lambs raised, but not treatment. In conclusion, immunization
      against either androstenedione or BMP15 increased ovulation rate. Androstenedione
      vaccination also increased the number of lambs weaned (P < 0.05). Bone
      morphogenetic protein 15 vaccination altered the pattern of the number of lambs
      weaned, but no increase in lamb production was observed as more ewes produced
      zero or three lambs. Overall, androstenedione or BMP15 vaccination did not
      significantly affect embryo or fetal survival or lamb performance independently
      of the effects of these treatments on ovulation rate. 

PMID- 24085417
TI  - Genotype-by-environment interaction of growth traits in rainbow trout
      (Oncorhynchus mykiss): a continental scale study.
AB  - Rainbow trout is a globally important fish species for aquaculture. However, fish
      for most farms worldwide are produced by only a few breeding companies. Selection
      based solely on fish performance recorded at a nucleus may lead to lower-than
      expected genetic gains in other production environments when genotype-by
      environment (G * E) interaction exists. The aim was to quantify the magnitude of
      G * E interaction of growth traits (tagging weight; BWT, harvest weight; BWH, and
      growth rate; TGC) measured across 4 environments, located in 3 different
      continents, by estimating genetic correlations between environments. A total of
      100 families, of at least 25 in size, were produced from the mating 58 sires and
      100 dams. In total, 13,806 offspring were reared at the nucleus (selection
      environment) in Washington State (NUC) and in 3 other environments: a
      recirculating aquaculture system in Freshwater Institute (FI), West Virginia; a
      high-altitude farm in Peru (PE), and a cold-water farm in Germany (GER). To
      account for selection bias due to selective mortality, a multitrait
      multienvironment animal mixed model was applied to analyze the performance data
      in different environments as different traits. Genetic correlation (rg) of a
      trait measured in different environments and rg of different traits measured in
      different environments were estimated. The results show that heterogeneity of
      additive genetic variances was mainly found for BWH measured in FI and PE.
      Additive genetic coefficient of variation for BWH in NUC, FI, PE, and GER were
      7.63, 8.36, 8.64, and 9.75, respectively. Genetic correlations between the same
      trait in different environments were low, indicating strong reranking (BWT: rg =
      0.15 to 0.37, BWH: rg = 0.19 to 0.48, TGC: rg = 0.31 to 0.36) across
      environments. The rg between BWT in NUC and BWH in both FI (0.31) and GER (0.36)
      were positive, which was also found between BWT in NUC and TGC in both FI (0.10)
      and GER (0.20). However, rg were negative between BWT in NUC and both BWH (-0.06)
      and TGC (-0.20) in PE. Correction for selection bias resulted in higher additive
      genetic variances. In conclusion, strong G * E interaction was found for BWT,
      BWH, and TGC. Accounting for G * E interaction in the breeding program, either by
      using sib information from testing stations or environment-specific breeding
      programs, would increase genetic gains for environments that differ significantly
      from NUC. 

PMID- 24085418
TI  - Feed intake, nutrient digestibility and ruminal fermentation activities in sheep
      fed peanut hulls treated with Trichoderma viride or urea.
AB  - This study aimed to assess impacts of fungal treatment on the nutritional value
      of peanut hulls (PH) or urea at the rate of 5 kg/100 g of PH. Fermented sugar
      beet pulp inoculated with Trichoderma viride was supplemented to PH at rates of
      5.0, 10.0 and 15.0 g/100 g air dry of PH and mixed well before aerobic incubation
      for 21 days. Organic matter (OM) content of PH declined with increased levels of
      fermented sugar beet pulp inoculums, while crude protein (CP), ether extract
      (EE), and ash increased. Fiber contents were decreased with both treatments of
      fermented sugar beet pulp and urea. Total N of PH increased with urea treatment,
      which reduced the true protein N to total protein N ratio. In sacco
      degradabilities of dry matter (DM), OM, and CP with urea treatment increased
      compared with fungal treatment. The DM intake of peanut hulls treated with fungus
      (PHF) was higher (P < 0.05) than with peanut hulls treated with urea (PHU).
      Digestibility of OM, CP, neutral detergent fiber, and non-fiber carbohydrate by
      native breed Ossimi sheep with PH were higher (P < 0.05) than with PH or urea
      treated PH. The intakes, losses, and balance of N increased (P < 0.01) with PHF
      versus PH feeding. Feeding PHF increased (P < 0.01) ruminal concentrations of NH3
      N, acetic acid, butyric acid, and the acetic to propionic acid ratio. Bacterial
      and protozoal counts increased (P < 0.05) with feeding PHF or PHU versus PH.
      Overall, this fungal treatment of peanut hulls created a higher nutritive value
      feed for ruminants. 

PMID- 24085419
TI  - Leptospirosis in sheep and goats under tropical conditions.
AB  - Inadequate management practices and poor reproductive performance have been
      reported as fundamental factors on reducing the levels of productivity in
      livestock. Different pathogens have been reported in small ruminants'
      herds/flocks with reproductive failures. The aim of the present study was to
      review aspects of leptospirosis in small ruminants, mainly its impact on
      reproduction and consequently on productivity of the herds/flocks under tropical
      conditions. Leptospiral infection in goats and sheep is common in several
      countries, and those species can also act as carriers of leptospires. Severe
      disease is often associated to young animals and is frequently associated to
      incidental serovars. In contrast, subclinical infection is mainly characterized
      by reproductive problems, such as infertility, abortion, occurrence of
      stillbirths, and weak lambs/goat kids. Moreover, laboratorial tests are essential
      to achieve an accurate diagnosis of the infection. Microscopic agglutination test
      is the most common indirect test of leptospirosis, being used worldwide. In small
      ruminants, PCR consists on a recommendable method for diagnosing animals that
      carry leptospires. Control of leptospirosis in small ruminants involves measures
      such as the identification and treatment of the carriers and other sources of
      infection, quarantine in acquired animals, and systematic immunization with
      commercial vaccines containing the circulating serovars in the herd/flock.
      Productivity of small ruminant breeding can dramatically increase with adequate
      sanitary conditions and control of leptospirosis. Immunization of all the animals
      combined to the treatment of carriers may successfully control the infection and
      importantly reduce the economic reproductive hazards that are observed under
      tropical conditions. 

PMID- 24085421
TI  - Meiotic pairing of B chromosomes, multiple sexual system, and Robertsonian fusion
      in the red brocket deer Mazama americana (Mammalia, Cervidae).
AB  - Deer species of the genus Mazama show significant inter- and intraspecific
      chromosomal variation due to the occurrence of rearrangements and B chromosomes.
      Given that carriers of aneuploidies and structural rearrangements often show
      anomalous chromosome pairings, we here performed a synaptonemal complex analysis
      to study chromosome pairing behavior in a red brocket deer (Mazama americana)
      individual that is heterozygous for a Robertsonian translocation, is a B
      chromosome carrier, and has a multiple sex chromosome system (XY1Y2). The
      synaptonemal complex in spermatocytes showed normal chromosome pairings for all
      chromosomes, including the autosomal and sex trivalents. The electromicrographs
      showed homology among B chromosomes since they formed bivalents, but they also
      appeared as univalents, indicating their anomalous behavior and non-Mendelian
      segregation. Thus, synaptonemal complex analysis is a useful tool to evaluate the
      role of B chromosomes and rearrangements during meiosis on the intraspecific
      chromosomal variation that is observed in the majority of Mazama species.

PMID- 24085422
TI  - Mutagenicity, genotoxicity, and scavenging activities of extracts from the soft
      coral Chromonephthea braziliensis: a possibility of new bioactive compounds.
AB  - Coral reefs are diverse ecosystems that have a high density of biodiversity
      leading to intense competition among species. These species may produce unknown
      substances, many with pharmacological value. Chromonephthea braziliensis is an
      invasive soft coral from the Indo-Pacific Ocean that is possibly transported by
      oil platforms and whose presence can be a threat to a region's biodiversity. This
      species produces secondary metabolites that are responsible for inducing damage
      to the local ecosystem. In the present study, extracts were prepared from dried
      colonies of C. braziliensis (solvents: hexane, dichloromethane, ethyl acetate,
      and methanol). We evaluated their mutagenicity using the Salmonella reverse
      mutation assay (TA97, TA98, TA100, and TA102 strains), their genotoxicity using
      the DNA breakage analysis and micronucleus assay, and scavenging activity using
      the 1,1-diphenyl-2-picrylhydrazyl-free radical assay. Cytotoxicity and
      mutagenicity were not observed for any of the extracts. Genotoxicity was observed
      for the dichloromethane, ethyl acetate, and methanol extracts at high
      concentrations, but no DNA damage was observed in the micronucleus assay.
      Scavenging activity was not detected. 

PMID- 24085420
TI  - Pathogenesis-targeted, disease-modifying therapies in Parkinson disease.
AB  - Parkinson disease is an inexorably progressive neurodegenerative disorder.
      Multiple attempts have been made to establish therapies for Parkinson disease
      which provide neuroprotection or disease modification-two related, but not
      identical, concepts. However, to date, none of these attempts have succeeded.
      Many challenges exist in this field of research, including a complex multisystem
      disorder that includes dopaminergic and non-dopaminergic features; poorly
      understood and clearly multifaceted disease pathogenic mechanisms; a lack of
      reliable animal models; an absence of effective biomarkers of disease state,
      progression, and target engagement; and the confounding effects of potent
      symptomatic therapy. In this article, we will review previous, ongoing, and
      potential future trials designed to alter the progressive course of the disease
      from the perspective of the targeted underlying pathogenic mechanisms. 

PMID- 24085423
TI  - Methylation regulation of liver-specific microRNA-122 expression and its effects
      on the proliferation and apoptosis of hepatocellular carcinoma cells.
AB  - The regulation mechanism and significance of microRNA-122 (miRNA-122) expression
      are unclear. The aim of this study was to investigate the effects of DNA
      methylation on liver-specific miRNA-122 expression, cell proliferation, and
      apoptosis in hepatocellular carcinoma. Methylation of the miRNA-122 promoter
      region was detected through methylation sequencing. The level of miRNA-122
      expression was measured using real-time quantitative polymerase chain reaction.
      The proliferation and apoptosis of hepatocellular cell lines were detected using
      flow cytometry and Cell Counting Kit-8 assays. Compared with those in human
      primary hepatocytes, methylation levels of the miRNA-122 promoter in the Huh7,
      HepG2, and QSG-7701 cell lines were significantly increased (P = 0.000).
      Similarly, levels of miRNA-122 expression in these cell lines significantly
      decreased (P = 0.007). After treatment with 5-aza-2-deoxycytidine, the Huh7 and
      HepG2 cell lines displayed a significantly lower degree of methylation (P = 0.038
      and 0.025), and the levels of miRNA-122 expression were significantly higher (P =
      0.008 and 0.003) than those in the blank group. Compared with the blank group,
      apoptosis of Huh7 and HepG2 cells was significantly increased (P = 0.001 and
      0.027). We concluded that the expression of miRNA-122 is regulated by DNA
      methylation and correlated with apoptosis of liver cancer cells. Methylation
      regulation of miRNA-122 expression might be involved in the development of
      hepatocellular carcinoma. 

PMID- 24085424
TI  - Molecular analysis of the SMN gene mutations in spinal muscular atrophy patients
      in China.
AB  - Spinal muscular atrophy (SMA) is one of the most common autosomal recessive
      diseases. Survival motor neuron1 (SMN1) is the SMA disease-determining gene. We
      examined the molecular basis of SMA in 113 Chinese SMA patients. Homozygous exon
      7 and 8 deletions in SMN1 were detected by PCR-RFLP. Heterozygous deletion of
      SMN1 was analyzed based on variation of the sequencing peak height of the two
      different base pairs of exons 7 and 8 between SMN1 and SMN2. Subtle mutation was
      detected by genomic sequencing in the patients with heterozygous deletion of
      SMN1. In our study, the rate of deletion of SMN1 exon 7 and/or 8 was 91.2%; the
      rate of subtle mutations was 1.8%. We detected the same subtle mutation
      (p.Leu228X) of SMN exon 5 in two patients (one type I, one type III). The
      p.Ser8LysfsX23 and p.Leu228X mutations accounted for 13 of the 23 families with
      subtle mutations reported in the SMN1 gene of Chinese SMA. This is the first
      report where the phenotype of SMA-type III is associated with p.Leu228X. We found
      two subtle mutation hotspots (p.Ser8LysfsX23 and p.Leu228X) of SMN1 exons 1 and 5
      in Chinese SMA patients. These two mutations have not been reported from America
      or Europe. It is proposed that the distribution of subtle mutations of SMN1 of
      SMA is associated with ethnicity or geographic origin. 

PMID- 24085425
TI  - Genetic determinants of the defense response of resistant and susceptible pepper
      (Capsicum annuum) cultivars infected with Phytophthora capsici (Oomycetes;
      Pythiaceae).
AB  - Based on culture isolation and morphological observation blight-infected pepper
      plants in Shaanxi Province, China, we identified the pathogen causing pepper
      phytophthora blight as Phytophthora capsici. Varieties that differed in
      resistance (CM334, PBC602, and B27) were inoculated with this pathogen. The root
      activity of resistant CM334 variety was the highest while that of susceptible B27
      variety was the lowest. Also, significant differences in the activity of POD,
      PAL, and beta-1,3-glucanase were found; there was a positive correlation between
      disease resistance and activity of these three enzymes. We inhibited mycelial
      growth and sporangia formation of P. capsici using crude beta-1,3-glucanase and
      PAL enzymes isolated from the resistant variety CM334 after it had been
      inoculated with P. capsici. These two enzymes had a synergistic effect on
      inhibition of P. capsici mycelial growth and sporangia formation. Expression of
      the defensive genes CaPO1, CaBGLU, CaBPR1, and CaRGA in the three varieties was
      higher in the leaves than in the roots. All three genes were upregulated in
      infected leaves and roots of the pepper plants, always expressing at higher
      levels in the resistant cultivar than in the susceptible cultivar, suggesting
      that the differences in resistance among the pepper genotypes involve differences
      in the timing and magnitude of the defense response. 

PMID- 24085426
TI  - Comparative and joint analyses of gene expression profiles under drought and
      rewatering in Arabidopsis.
AB  - Drought is a major limiting factor in crop production. Rewatering is a process
      opposite to drought, allowing plants to recover to their normal physiological
      state. To understand more thoroughly the set of genes involved in plant response
      to drought, we comparatively and jointly analyzed the microarray data of drought
      and rewatering experiments in Arabidopsis. A total of 3833 differentially
      expressed genes (DEGs) were identified. Among them, ~74% were proven to be co
      regulated by drought and rewatering. Drought and rewatering showed contrary
      regulatory effects on almost all of these co-regulated genes. Only ~6% of the
      DEGs were significantly regulated by drought alone, and the remaining ~20% were
      significantly regulated by rewatering alone. However, gene ontology analysis
      suggested that those "rewatering-only" genes also appeared to be related, either
      directly or indirectly, to drought response. 

PMID- 24085427
TI  - Physiological quality and gene expression related to heat-resistant proteins at
      different stages of development of maize seeds.
AB  - We quantified and characterized the expression of heat-resistant proteins during
      seed development of maize lines with distinct levels of tolerance to high drying
      temperature. A corn field was planted for multiplication of seeds of different
      lines, two tolerant and two non-tolerant to high drying temperatures. Harvest of
      the seeds was carried out at various stages of development and they were then
      subjected to tests of moisture content, germination, first count of germination,
      accelerated aging, and cold test. The seeds were stored in a freezer for later
      analysis of expression of heat-resistant proteins by means of real-time PCR,
      electrophoresis, and spectrophotometry. We observed that heat-resistant proteins
      are expressed in a differential manner in seeds from different lines and at
      different stages of development. The expression of heat-resistant proteins was
      earlier in lines tolerant to high drying temperatures. Greater germination and
      vigor values was found for seeds collected at the last stage of development. 

PMID- 24085428
TI  - Significant association of APOA5 and APOC3 gene polymorphisms with meat quality
      traits in Kele pigs.
AB  - Apolipoprotein A5 (APOA5) and C3 (APOC3) genes are involved in the PPAR lipid
      metabolism pathway and thus associated with elevated triglyceride levels.
      However, whether APOA5 and APOC3 genetic polymorphisms affect intramuscular fat
      deposition and other meat quality traits remains unknown in pigs. One hundred and
      seventy-one Kele pigs were sampled to investigate genetic variants in the APOA5
      and APOC3 genes and their association with seven pork quality traits. We
      identified 5 single nucleotide polymorphisms (SNPs) in the promoter region of the
      APOA5 gene and 17 SNPs in the APOC3 gene. Linkage disequilibrium analysis
      revealed 5 complete linkage disequilibria among these 22 SNPs. We found that 10
      SNPs were significantly correlated with meat quality traits, including the
      mutation A5/-769 in the APOA5 gene, which was significantly associated with
      cooked weight percentage, and 9 SNPs in the APOC3 gene that were significantly
      associated with drip loss rate, meat color value of longissimus dorsi muscle and
      shear force. Therefore, these SNP markers will be useful for marker-assisted
      selection for improved pork quality. 

PMID- 24085429
TI  - Molecular cloning, polymorphisms, and association analysis of the promoter region
      of the STAM2 gene in Wuchuan Black cattle.
AB  - The STAM protein plays an important role in the cytokine-related JAK/STAT
      pathway. We selected the STAM2 gene as a candidate gene that could be linked to
      growth performance in analysis of a Chinese cattle breed (Wuchuan Black cattle).
      We examined genetic variants in the promoter region of the STAM2 gene and their
      associations with eight growth traits in 159 individuals. Seven SNPs, which
      included six new SNPs for the SNP database, were found. The core promoter region
      was identified with a bioinformatic software. This analysis also showed that the
      SNPs have a significant influence on the function and structure of the STAM2
      promoter in terms of RNA secondary structure, CpG island, and transcription
      factor binding sites. Association analysis demonstrated that G-102A is
      significantly associated with withers height, heart girth, cannon circumference,
      chest width, and hip height in this population, which leads us to suggest that G
      102A is a useful SNP marker for cattle growth performance. Animals with the
      genotype AA had higher mean values for withers height, cannon circumference,
      chest width, and hip height than those with GG and AG genotypes. This SNP of the
      STAM2 gene could be applied in marker-assisted selection for improving growth
      performance in cattle. 

PMID- 24085430
TI  - Potential role of Atp5g3 in epigenetic regulation of alcohol preference or
      obesity from a mouse genomic perspective.
AB  - The mitochondrial ATP synthase, subunit c, isoform 3 gene (Atp5g3) encodes
      subunit 9, the subunit of the multisubunit enzyme that catalyzes ATP synthesis
      during oxidative phosphorylation in mitochondria. According to the Ensembl
      database, Atp5g3 in mice is located on chromosome 2 between 73746504 and 73749383
      bp, within the genomic regions of two sets of quantitative trait loci - alcohol
      preference and body weight. Both of those traits are more influenced by
      epigenetic factors than many other traits are. Using currently available
      phenotype and gene expression profiles from the GeneNetwork database, we obtained
      correlations between Atp5g3 and alcoholism- and obesity-relevant phenotypes. The
      correlation in expression levels between Atp5g3 and each of its 12 partner genes
      in the molecular interaction are different in various tissues and genes.
      Transcriptome mapping indicated that Atp5g3 is differentially regulated in the
      hippocampus, cerebellum, and liver. Owing to a lack of known polymorphisms of
      Atp5g3 among three relevant mouse strains, C57BL/6J (B6), DBA/2J (D2), and BALB/
      cJ, the molecular mechanism for the connection between Atp5g3 and alcoholism and
      body weight requires further investigation. 

PMID- 24085431
TI  - Association of the interleukin-28B gene polymorphism with development of
      hepatitis virus-related hepatocellular carcinoma and liver cirrhosis: a meta
      analysis.
AB  - We examined the association of the interleukin-28B (IL-28B) gene rs12979860 T/C
      polymorphism with development of hepatitis virus-related hepatocellular carcinoma
      (HCC) and liver cirrhosis (LC). Two investigators independently searched the
      PubMed, Elsevier, EMBASE, Web of Science, Wiley Online Library, and Chinese
      National Knowledge Infrastructure data bases. Pooled odds ratios (ORs) and 95%
      confidence intervals (95%CIs) for rs12979860 and HCC/LC were calculated in a
      fixed-effect model (the Mantel-Haenszel method) and a random-effect model (the
      DerSimonian and Laird method) when appropriate. This meta-analysis included 7
      eligible studies, with 1152 HCC and/or LC cases and 1326 controls. Overall, the
      rs12979860 T/C polymorphism was significantly associated with risk of hepatitis
      virus-related HCC and LC development (TT vs CC+CT, pooled OR = 1.597, 95%CI =
      1.254-2.036). When they were grouped by type of hepatitis virus, similar results
      were found for hepatitis C virus-related groups (TT vs CC+CT, pooled OR = 1.732,
      95%CI = 1.343-2.235, P value < 0.0001). In the overall analysis, the IL-28B
      rs12979860 T/C polymorphism was identified as a genetic risk factor for hepatitis
      virus-related HCC and LC development. A significant increase in the frequency of
      the T/T genotype was detected from chronic hepatitis to HCC and LC. 

PMID- 24085432
TI  - Antigenotoxic and anticytotoxic activity of Duguetia furfuracea in bacteria and
      mice.
AB  - Duguetia furfuracea (St. Hil.) Benth & Hook f. (1862), popularly known as "sofre
      do-rim-quem-quer" and "araticum-seco", is a shrub of the Annonaceae family that
      grows in several regions of Brazil. Infusions of its leaves and twigs are used in
      folk medicine to treat rheumatism and renal colic, whereas the seed powder is
      mixed with water to treat pediculosis. Studies on the plant have reported
      biological activities with cytotoxic, antitumoral, trypanocidal, leishmanicidal,
      antiplasmodial, and antiprotozoal effects. Our previous studies using a prophage
      lambda induction test (SOS-Inductest) and the micronucleus assay demonstrated
      that D. furfuracea lyophilized leaf extract (DFE) displayed cytotoxic but not
      genotoxic activity. In the present study, antigenotoxic and anticytotoxic
      activities of DFE were evaluated using SOS-Inductest and mouse bone marrow
      micronucleus tests. Our results showed that DFE decreased the induction of either
      prophage lambda (P < 0.05; SOS-Inductest) or micronucleated polychromatic
      erythrocytes (P < 0.05; micronucleus test) at all doses, suggesting antigenotoxic
      activity in both tests. On assessing the anticytotoxic activity of DFE, a
      significant increase in the number of bacteria at lower doses (P < 0.05) as well
      as a significant increase in the polychromatic and normochromatic erythrocyte
      ratio were observed (P < 0.05), demonstrating the anticytotoxic activity of DFE.
      Thus, D. furfuracea displayed antigenotoxic and anticytotoxic activity in both
      assays. 

PMID- 24085433
TI  - Chromosomal characteristics of a Brazilian whip spider (Amblypygi) and
      evolutionary relationships with other arachnid orders.
AB  - We analyzed mitotic and meiotic cells of a Brazilian amblypygid, Heterophrynus
      longicornis, using conventional and molecular cytogenetic techniques (Giemsa
      staining, C-banding, Ag-NOR, and FISH with rDNA probe). This is the first study
      that focuses solely on amblypygid chromosomes; it was undertaken to add data on
      cytogenetic knowledge of this group and contribute to the understanding of
      chromosome evolution in the Arachnida. We found 2n = 66 for male and female
      individuals, monocentric chromosomes, and absence of morphologically
      differentiated sex chromosomes. C-banding showed heterochromatin in the
      pericentromeric region of most chromosomes. Mitotic and meiotic nuclei submitted
      to silver impregnation and FISH revealed, respectively, Ag-NORs and ribosomal
      genes in the terminal region of two chromosome pairs. Most chromosome features
      that we observed in H. longicornis are shared with species of other arachnid
      orders; however, the absence of morphologically differentiated sex chromosomes in
      amblypygid contrasts with the remarkable variety of sex chromosome systems
      recorded for the Araneae. Consequently, we conclude that analysis of species of
      the Tetrapulmonata clade is useful for understanding the trends of sex chromosome
      evolution in this arachnid group. 

PMID- 24085434
TI  - Analysis of FOS, BTG2, and NR4A in the function of renal medullary hypertension.
AB  - The aim of this study was to identify differentially expressed genes (DEGs) in
      renal medullary hypertension and reveal their pathogenic mechanisms. We
      downloaded the gene expression profile of GSE28360 from the Gene Expression
      Omnibus database. The profile included 14 samples (5 normal and 9 hypertension).
      The DEGs in normal and disease samples were distinguished with a false-discovery
      rate threshold of <0.05 and a fold-change value of >2 or <-2. We put the selected
      genes into the online program String 8.3 to obtain the protein-protein
      interaction network and selected the hub proteins. These hub proteins were then
      placed in the PANTHER database to determine hub protein-related pathways and
      explain their functions. Finally, we cleared up the single-nucleotide
      polymorphisms (SNPs) of the hub genes via combing with the National Center for
      Biotechnology SNP database. A total of 13 genes were identified as DEGs between
      normal and disease samples. Five selected hub proteins, B-cell translocation gene
      2 (BTG2), FBJ murine osteosarcoma viral oncogene homolog (FOS), nuclear receptor
      subfamily 4, group A, member 1 (NR4A1), NR4A member 2 (NR4A2), and NR4A member 3
      (NR4A3), were mainly related to angiogenesis and B-cell activation. After SNP
      analysis, 103, 103, 595, 150, and 493 SNPs were found to correspond to BTG2, FOS,
      NR4A1, NR4A2, and NR4A3, respectively. Our results suggest that pathways of
      angiogenesis and B-cell activation may involve in the progression of renal
      medulla hypertension. 

PMID- 24085435
TI  - Influences of species mixture on biomass of Masson pine (Pinus massoniana Lamb)
      forests.
AB  - The effect of tree diversity on productivity in subtropical forests in China is
      poorly understood. We investigated the biomasses of trees, understory vegetation,
      coarse roots, and fine roots with varying proportions of Pinus massoniana, mixed
      with other tree species in stands of the same age, to examine the effects of tree
      diversity. With an increase of P. massoniana proportion, the tree and understory
      biomasses increased at first, and then gradually decreased. As expected, the
      biomass of fine roots decreased with soil depth. Stands with 40 to 60% P.
      massoniana had the highest biomass, whereas stands with <20% P. massoniana had
      the least biomass. Stands with <20% P. massoniana had the least understory
      biomass, whereas those with 20 to 40% Masson pine had the least fine root
      biomass. 

PMID- 24085436
TI  - Microsatellite markers in Paulownia kawakamii (Scrophulariaceae) and cross
      amplification in other Paulownia species.
AB  - Paulownia kawakamii is a fast-growing timber tree. In this study, 21 primer sets
      were developed using an enriched genomic library. The genetic diversity was
      measured in one P. kawakamii population. The number of alleles per locus ranged
      from 2 to 19. The observed and expected heterozygosities varied from 0.158 to
      0.842 (mean = 0.421) and from 0.376 to 0.952 (mean = 0.771), respectively. All 21
      loci were also polymorphic in closely related species (P. tomentosa, P. elongata,
      and P. fortunei). The described markers will be useful in future population
      genetic studies and molecular breeding of these Paulownia species. 

PMID- 24085437
TI  - Phylogenetic relationships among Octopodidae species in coastal waters of China
      inferred from two mitochondrial DNA gene sequences.
AB  - Octopus in the family Octopodidae (Mollusca: Cephalopoda) has been generally
      recognized as a "catch-all" genus. The monophyly of octopus species in China's
      coastal waters has not yet been studied. In this paper, we inferred the phylogeny
      of 11 octopus species (family Octopodidae) in China's coastal waters using
      nucleotide sequences of two mitochondrial DNA genes: cytochrome c oxidase subunit
      I (COI) and 16S rRNA. Sequence analysis of both genes revealed that the 11
      species of Octopodidae fell into four distinct groups, which were genetically
      distant from one another and exhibited identical phylogenetic resolution. The
      phylogenies indicated strongly that the genus Octopus in China's coastal waters
      is also not monophyletic, and it is therefore clear that the Octopodidae
      systematics in this area requires major revision. It is demonstrated that partial
      sequence information of both the mitochondrial genes 16S rRNA and COI could be
      used as diagnostic molecular markers in the identification and resolution of the
      taxonomic ambiguity of Octopodidae species. 

PMID- 24085438
TI  - Experimental strategies in carrying out VCU for tobacco crop I: plot design and
      size.
AB  - We aimed to establish standards for tobacco Valor de Cultivo e Uso (VCU) in
      Brazil. We obtained information regarding the size and design of plots of two
      varietal groups of tobacco (Virginia and Burley). Ten inbred lines of each
      varietal group were evaluated in a randomized complete block design with four
      replications. The plot contained 42 plants with six rows of seven columns each.
      For each experiment plant, considering the position of the respective plant in
      the plot (row and column) as a reference, cured leaf weight (g/plant), total
      sugar content (%), and total alkaloid content (%) were determined. The maximum
      curvature of the variations in coefficients was estimated. Trials with the number
      of plants per plot ranging from 2 to 41 were simulated. The use of a border was
      not justified because the interactions between inbred lines x position in the
      plots were never significant, showing that the behavior of the inbred lines
      coincided with the different positions. The plant performance varied according to
      the column position in the plot. To lessen the effect of this factor, the use of
      plots with more than one row is recommended. Experimental precision, evaluated by
      the CV%, increased with an increase in plot size; nevertheless, the maximum
      curvature of the variation coefficient method showed no expressive increase in
      precision if the number of plants was greater than seven. The result in
      identification of the best inbred line, in terms of the size of each plot,
      coincided with the maximum curvature method. 

PMID- 24085439
TI  - Genetic structure of Aedes aegypti populations determined using pairwise
      comparisons.
AB  - The biological characteristics of Aedes aegypti (Diptera, Culicidae), which is a
      vector of dengue and yellow fever, make this organism a good model for studying
      population structure and the events that may influence it under the effect of
      human activity. We assessed the genetic variability of five A. aegypti
      populations using RAPD-PCR technique and six primers. Four populations were from
      Brazil and one was from the USA. A total of 165 polymorphic DNA loci were
      generated. Considering the six primers and the five populations, the mean value
      of inter-population genetic diversity (Gst) was 0.277, which is considered high
      according to the Wright classification. However, pairwise comparisons of the
      populations gave variable Gst values ranging from 0.044 to 0.289. This variation
      followed the population's geographic distance to some extent but was also
      influenced by human activity. The lowest Gst values were obtained in the
      comparison of populations from cities with intensive commercial and medical
      contacts. These mosquito populations were previously classified as insecticide
      resistant, susceptible, or with decreased susceptibility; this parameter
      apparently had an effect on the Gst values obtained in the pairwise comparisons. 

PMID- 24085440
TI  - Development of polymorphic microsatellite markers for Dioscorea zingiberensis and
      cross-amplification in other Dioscorea species.
AB  - Dioscorea zingiberensis C.H. Wright (Dioscoreaceae) is an endemic species in
      central and southwestern China. In order to study the genetic diversity and
      population structure of this species, 19 novel polymorphic microsatellite loci
      were developed using a dual-suppression PCR technique. The number of alleles per
      locus ranged from 3 to 21, with an average of 9.53. All the markers showed high
      transferability in cross-species amplification in other species of sect.
      Stenophora. 

PMID- 24085441
TI  - Identification of miRNAs and their targets in wheat (Triticum aestivum L.) by EST
      analysis.
AB  - MicroRNAs (miRNAs) are a newly discovered class of noncoding small RNAs that
      regulate gene expression by directing target mRNA cleavage or translational
      inhibition. A large number of miRNAs have been identified in plants. Increasing
      evidence has shown that miRNAs play multiple roles in plant biological processes.
      So far, identification of miRNAs has been limited to a few model plant species,
      whose genomes have been sequenced. Wheat (Triticum aestivum L.) is one of the
      most important cereal crops worldwide. To date, only a few conserved miRNAs have
      been predicted in wheat. Here, we showed the conserved miRNAs identified in wheat
      by expressed sequence tag (EST) analysis. All previously known miRNAs from
      Arabidopsis, rice, and other plant species were used in a BLAST search against
      the wheat EST database to identify novel wheat miRNAs by a series of filtering
      criteria. By this strategy, we identified 62 conserved miRNAs, belonging to 30
      miRNA families, 48 of which were newly discovered in wheat. These newly
      identified wheat miRNAs may regulate 287 potential targets, which are involved in
      development, signal transduction, metabolic pathways, disease resistance, ion
      transportation, and environmental stress response. 

PMID- 24085442
TI  - Relationship between multidrug resistance 1 polymorphisms and the risk of
      prostate cancer in Chinese populations.
AB  - Prostate cancer is one of the most common malignancies in men. The multidrug
      resistance 1 gene (MDR1) is an important candidate gene for prostate cancer. The
      aim of this study was to evaluate the association between MDR1 gene polymorphisms
      and the risk of prostate cancer. MDR1 gene polymorphism and its association with
      the risk of prostate cancer were investigated in 357 Chinese men. A novel
      c.1465C>T polymorphism was detected with created restriction site-polymerase
      chain reaction and DNA sequencing. We found a significantly increased risk of
      prostate cancer in the homozygote comparison [TT vs CC: odds ratio (OR) = 2.300,
      95% confidence interval (95%CI) = 1.261-4.196, chi-square = 7.53, P = 0.007],
      heterozygote comparison (TC vs CC: OR = 1.667, 95%CI = 1.049-2.648, chi-square =
      4.71, P = 0.030), dominant model (TT/TC vs CC: OR = 1.835, 95%CI = 1.197-2.815,
      chi-square = 7.81, P = 0.005), recessive model (TT vs TC/CC: OR = 1.776, 95%CI =
      1.023- 3.085, chi-square = 4.23, P = 0.041), and allele contrast (T vs C: OR =
      1.625, 95%CI = 1.199-2.202, chi-square = 9.87, P = 0.002). These findings
      suggested that the c.1465C>T polymorphism of MDR1 may be risk factors for
      prostate cancer in Chinese men.

PMID- 24085443
TI  - Genetic polymorphisms of the TLR4 gene and their association with susceptibility
      to type 2 diabetes mellitus in the Chinese population.
AB  - Toll-like receptor 4 (TLR4) is potentially an important gene affecting the
      susceptibility to type 2 diabetes mellitus (T2DM). The objective of this study
      was to evaluate whether genetic polymorphisms of the TLR4 gene are associated
      with T2DM susceptibility. This potential association was analyzed in 668 T2DM
      patients and 672 healthy controls by polymerase chain reaction-restriction
      fragment length polymorphism and DNA sequencing methods. Two novel genetic
      polymorphisms (g.12375A>G and g.14367G>A) were investigated, and our data support
      the idea that the g.14367G>A variant significantly increased susceptibility to
      T2DM in homozygote comparison (AA vs GG: OR = 2.396, 95%CI = 1.682-3.413, P <
      0.0001), heterozygote comparison (GA vs AA: OR = 1.322, 95%CI = 1.050-1.664, P =
      0.0175), dominant model (AA/GA vs GG: OR = 1.511, 95%CI = 1.217-1.876, P =
      0.0002), recessive model (AA vs GA/GG: OR = 2.093, 95%CI = 1.496-2.927, P <
      0.0001), and allele contrast (A vs G: OR = 1.503, 95%CI = 1.279-1.766, P <
      0.0001). The allele A of g.14367G>A variants may contribute to the susceptibility
      to T2DM. However, we failed to detect a similar significantly increased
      susceptibility to T2DM in the g.12375A>G variant. Our findings suggest that the
      g.14367G>A genetic polymorphism of the TLR4 gene is associated with the
      susceptibility to T2DM in the population studied.

PMID- 24085444
TI  - Expression of a GDP-L-galactose phosphorylase-like gene in a Chinese wild Vitis
      species induces responses to Erysiphe necator and defense signaling molecules.
AB  - Using rapid amplification of cDNA ends, a full-length cDNA sequence of a GDP-L
      galactose phosphorylase-like gene was isolated from leaves infected by Erysiphe
      necator in the Chinese wild (Vitis pseudoreticulata) clone, 'Baihe-35-1', an E.
      necator-resistant genotype. The full-length cDNA, designated as VpVTC, comprised
      1943 bp and putatively encodes a 453-amino acid polypeptide containing an HIT
      motif. The deduced amino acid sequence showed high similarity with that of VTC
      genes from other plants. The expression of VpVTC, determined by reverse
      transcriptase-polymerase chain reaction, was induced by E. necator and defense
      signaling molecules, including salicylic acid, methyl jasmonate, and ethephon, in
      'Baihe-35-1', the V. quinquangularis genotype 'Shang-24', and the E. necator
      susceptible V. pseudoreticulata genotype, 'Hunan-1'. Transcript levels of VpVTC
      correlated well with the degree of disease resistance in the 3 genotypes. Maximum
      induction of VpVTC by E. necator (>7-fold at 96 h post-inoculation) occurred in
      'Baihe-35-1', which also showed the fastest response to signaling molecules.
      Upregulating the expression of VpVTC in 'Baihe-35-1' resulted in a gradual
      increase in the ascorbic acid concentration of leaves inoculated with E. necator.
      Furthermore, VpVTC was expressed in leaves, stems, inflorescence, tendrils, and
      fruit at all developmental stages, with the highest level occurring in fruit 35
      days after flowering. 

PMID- 24085445
TI  - Fine mapping and characterization of a novel dwarf and narrow-leaf mutant dnl1 in
      rice.
AB  - Plant height is one of the most important agronomic traits of rice (Oryza
      sativa). Dwarf mutants are ideal materials for research on the mechanisms of
      regulation of rice plant height. We examined a new dwarf and narrow-leaf mutant
      dnl1. Phenotypic analysis showed that the dnl1 mutant has a thinner culm and more
      tillers, but the number of grains per panicle, the seed setting rate and the
      grain weight of dnl1 mutant were found to be significantly lower than in the wild
      type. Based on scanning electron microscopic observations, the number of cells in
      the y-axis in internodes was significantly lower than in the wild-type. In
      phytohormone induction experiments, dnl1 was gibberellic acid-insensitive. The
      expression of some genes involved in the gibberellins metabolic pathways was
      affected in the dnl1 mutant, based on the real-time PCR analysis, suggesting that
      the dnl1 gene likely plays a role in gibberellin metabolic pathways. Genetic
      analysis showed that the dwarf and narrow leaf phenotype is controlled by a novel
      single recessive gene, here referred to as the dwarf and narrow leaf 1 (dnl1),
      which is located within the region between markers Ind12-11 and RM8214 on the
      short arm of chromosome 12. By means of fine-mapping strategy, the dnl1 gene was
      localized within an interval of 285.75 kb physical distance. These results will
      be useful for dnl1 gene cloning and to improve our understanding of the molecular
      mechanisms involved in the regulation of growth and development of rice. 

PMID- 24085446
TI  - Effect of glycerol on GHR and IGF-1 gene expression in breast muscle and on
      growth of Japanese meat quails.
AB  - We evaluated messenger RNA (mRNA) expression of the growth-hormone (GHR) and
      insulin-like growth factor (IGF-1) genes in 28-day-old Japanese meat quails fed
      diets containing 0, 8, or 12% dietary glycerol in substitution of corn. Total RNA
      was extracted from the breast muscle and the DNA was amplified with specific
      primers using real-time PCR. Feed conversion ratio and feed intake were
      evaluated. The birds fed 8 and 12% glycerol presented higher IGF-1 mRNA
      expression [0.059 and 0.049 arbitrary units (AU), respectively] relative to those
      not fed with glycerol (0.029 AU), while 12% glycerol reduced GHR mRNA expression
      (0.022 AU). Dietary inclusion of 8% glycerol promoted similar performance results
      (feed conversion) as the diet with no glycerol. We conclude that inclusion of
      glycerol in the diet affects GHR and IGF-1 gene expression in Japanese meat
      quails. However, considering the performance results and the expression of the
      GHR and IGF-1 genes, 8% glycerol may be safely included in the diet of meat
      quails. 

PMID- 24085448
TI  - Development of highly polymorphic EST-SSR markers and segregation in F1 hybrid
      population of Vitis vinifera L.
AB  - The objectives of this investigation were to develop and validate the expressed
      sequence tag (EST)-simple sequence repeat (SSR) markers from large EST sequences,
      and to study the segregation and distribution of SSRs within two grapevine
      parental lines. In total, 94 F1 lines crossed between "Early Rose" and "Red
      Globe" were studied. Approximately 2100 EST-SSR sequences of Vitis vinifera L.
      were searched for SSRs and analyzed for the design of polymerase chain reaction
      (PCR) primers amplifying the SSR-rich regions. Trinucleotide repeats were found
      to be the most abundant, followed by other nucleotide repeats. A total of 182 SSR
      primer pairs were first developed for the study on the parental polymorphism.
      Among the 182 SSR primers, 142 primer pairs (78%) could amplify the anticipated
      PCR products, among which only 52 primer pairs (36.62%) showed polymorphism
      between the two parents. These polymorphic bands were further surveyed among the
      94 F1 lines, and the results showed that a total of 162 bands were amplified, and
      98 of them were polymorphic in both parents (60.86% polymorphism), with an
      average of 1.88 polymorphic DNA bands for each primer pair. After testing with
      the chi-square test, 33 of the clearly amplified polymorphic bands followed a 3:1
      ratio, and 37 followed a 1:1 ratio. The rest showed distorted segregation ratios.

PMID- 24085447
TI  - Cytogenetic toxicity and gonadal effects of 17 alpha-methyltestosterone in
      Astyanax bimaculatus (Characidae) and Oreochromis niloticus (Cichlidae).
AB  - The synthetic hormone, 17-alpha-methyltestosterone (MT), is used in fish
      hatcheries to induce male monosex. Androgenic effects on various fish species
      have been reported; however, few studies have assessed possible genotoxic
      effects, although there are concerns about such effects in target and non-target
      species. We evaluated genotoxic and gonadal effects of MT in adult tilapia
      (Oreochromis niloticus) and Astyanax bimaculatus (a common native non-target fish
      in Brazil). Fish were fed for 28 days with ration containing MT (60 mg/L), a
      normal dose used in fish farming. Evaluation of MT genotoxicity was carried out
      through micronucleus test, nuclear abnormality, and comet assay analyses on
      peripheral erythrocyte cells collected by cardiac puncture. There were no
      significant differences in micronucleus frequencies and DNA damage in both
      species; however, MT caused cytogenetic toxicity in the non-target species, A.
      bimaculatus, with significantly increased erythrocyte nuclear abnormalities.
      Histopathological analyses of the female gonads of O. niloticus revealed that MT
      significantly inhibited the development of mature oocytes, while in A.
      bimaculatus it provoked significant inhibition of spermatozoa production. We
      concluded that discharge of fish-hatcheries water onto the surface of aquatic
      ecosystems should be avoided due to risks to reproduction of native species. 

PMID- 24085449
TI  - Polymorphisms in the endothelial nitric oxide synthase gene associated with
      recurrent miscarriage.
AB  - Endothelial nitric oxide synthase (eNOS) is an enzyme that influences placental
      human chorionic gonadotropin production during gestation. Previous studies have
      indicated an association between eNOS activity, implantation, and maintenance of
      pregnancy, but proposed associations between polymorphisms of the eNOS gene and
      recurrent miscarriage (RM) are controversial. To identify markers contributing to
      the genetic susceptibility to RM, we examined the potential association between
      RM and 8 single nucleotide polymorphisms (SNPs; rs1799983, rs2070744, rs11771443,
      rs3918188, rs2853796, rs7830, rs1541861, and rs2853792) of the eNOS gene using
      the MassARRAY system (Sequenom, USA). The enrolled participants included 192 RM
      patients and 201 women with normal fertility as controls. The results showed that
      rs1799983 at exon 7 of the eNOS gene was significantly associated with RM
      (genotype: chi-square = 15.071, P = 0.001; allele: chi-square = 6.250, P =
      0.016). Another significant association was observed for rs11771443 in the
      promoter (genotype: chi-square = 6.259, P = 0.044; allele: chi-square = 7.076, P
      = 0.008). Furthermore, strong linkage disequilibrium was observed in 3 blocks (D'
      > 0.9), and significantly fewer T-T-G haplotypes (chi-square = 5.981, P = 0.015)
      residing in block 1 were found in RM patients. These findings point to a role for
      eNOS gene polymorphisms in RM in the Chinese Han population and may be
      informative for future genetic or neurobiological studies of RM. 

PMID- 24085450
TI  - Antigenotoxic, and anticytotoxic activities of an ethanolic extract of Lafoensia
      pacari (Lythraceae) stem bark in bacteria and mice.
AB  - Lafoensia pacari (Lythraceae), popularly known in Brazil as "pacari", is a small
      tree native to the Cerrado that is used in folk medicine to treat cancer and as
      an anti-inflammatory and cicatrizing agent. We evaluated the genotoxic,
      cytotoxic, antigenotoxic, and anticytotoxic activities of an ethanol extract of
      L. pacari stem bark (EESB) using the Ames test and the mouse bone marrow
      micronucleus test. In the Ames test, EESB did not significantly increase the
      number of His(+) revertants in Salmonella typhimurium tester strains TA98 and
      TA100 at all doses, demonstrating lack of mutagenicity. Only the highest dose of
      EESB significantly increased the micronucleated polychromatic erythrocyte
      frequency in the micronucleus test, indicating mild genotoxicity. EESB produced a
      mutagenic index lower than the negative control in the Ames test. In the
      micronucleus test, at all doses, EESB caused a significant decrease in the
      polychromatic/normochromatic erythrocyte ratio (PCE/NCE) at 24 h compared with
      the negative control. EESB co-administered together with the respective positive
      control caused a significant decrease in the number of His(+) revertant colonies
      in the Ames test and in the frequency of micronucleated polychromatic
      erythrocytes in the micronucleus test, demonstrating a DNA protector effect. EESB
      co-administered with mitomycin C significantly increased the PCE/NCE ratio at all
      doses, showing an anticytotoxic effect. We conclude that EESB has antigenotoxic
      and anticytotoxic properties. 

PMID- 24085451
TI  - Bovine herpesvirus type 5 infection regulates Bax/BCL-2 ratio.
AB  - Bovine herpesvirus 5 (BoHV-5) is an alpha-herpesvirus that causes neurological
      disease in young cattle and is also occasionally involved in reproductive
      disorders. Although there have been many studies of the apoptotic pathways
      induced by viruses belonging to the family Herpesviridae, there is little
      information about the intrinsic programmed cell death pathway in host-BoHV-5
      interactions. We found that BoHV-5 is able to replicate in both mesenchymal and
      epithelial cell lines, provoking cytopathology that is characterized by cellular
      swelling and cell fusion. Viral antigens were detected in infected cells by
      immunofluorescence assay at 48 to 96 h post-infection (p.i.). At 48 to 72 h p.i.,
      anti-apoptotic BCL-2 antigens were found at higher levels than Bax antigens; the
      latter is considered a pro-apoptotic protein. Infected cells had increased BCL-2
      phenotype cells from 48 to 96 h p.i., based on flow cytometric analysis. At 48 to
      96 h p.i., Bax mRNA was not expressed in any of the infected cell monolayers. In
      contrast, BCL-2 mRNA was found at high levels at all p.i. in both types of cells.
      BoHV-5 replication apparently modulates BCL-2 expression and gene transcription,
      enhancing production of virus progeny. 

PMID- 24085452
TI  - Genomic DNA isolation of Acrocomia aculeata (Arecaceae) from leaf and stipe
      tissue samples for PCR analysis.
AB  - Macaw palm, Acrocomia aculeata is an oleaginous species of the Arecaceae family;
      it has been identified as one of the most promising plants for sustainable
      production of renewable energy, especially biodiesel. We developed an efficient
      protocol of genomic DNA extraction for A. aculeata using leaf and stipe tissues,
      based on the cationic hexadecyltrimethylammonium bromide method, and we evaluated
      the quantity, purity, and integrity of the resultant DNA. We also determined
      whether these procedures interfere with PCR amplification using SSR molecular
      markers. The lowest concentration of DNA was obtained from stipe tissues (135
      ng/MUL), while fresh leaf tissues provided the highest concentration of DNA (650
      ng/MUL). Good quality DNA was obtained from fresh leaf, lyophilized leaf, and
      stipe tissues (relative purity, 1.79-1.89 nm). Differences in quantity and
      quality of DNA extracted from different tissues did not interfere with general
      patterns of PCR amplification based on SSR markers. 

PMID- 24085453
TI  - Association of the G403A polymorphism in the RANTES gene with coronary artery
      disease: a meta-analysis.
AB  - The G403A polymorphism in the RANTES (regulated on activation normal T cell
      expressed and secreted) gene has a key role in the expression of RANTES, which
      has been detected in a range of cells in atherosclerotic plaque. However, the
      association of this polymorphism with the risk of coronary artery disease (CAD)
      remains controversial. A meta-analysis was performed to assess the association of
      the G403A polymorphism in the RANTES gene with the risk of CAD. A comprehensive
      search was conducted to identify all studies published on the association of the
      RANTES gene G403A polymorphism with CAD risk. The fixed or random-effect pooled
      measure was adopted based on a heterogeneity test among studies, which was
      evaluated using I(2). Potential sources of between-study heterogeneity were
      explored using meta-regression analysis. Publication bias was estimated with
      Begg's rank correlation method. Eight articles were included in this meta
      analysis, with 4601 CAD cases and 2522 controls. No significant association of
      RANTES gene G403A polymorphism with CAD was identified in any of the codominant,
      dominant, recessive, homozygote, or heterozygote inheritance models. No evidence
      of publication bias was detected. The meta-analysis suggested that the A allele
      of the G403A polymorphism in the RANTES gene has no effect on the risk of CAD.
      This relationship needs to be confirmed by further studies. 

PMID- 24085454
TI  - Significantly association of diabetes mellitus with CTLA-4 gene polymorphisms
      based on a meta-analysis of epidemiological evidence in Asians and non-Asians.
AB  - We evaluated association of polymorphisms in the CTLA-4 gene with the risk of
      type 1 diabetes mellitus. Comprehensive meta-analysis was applied to case-control
      studies of the association between CTLA-4 and type 1 diabetes mellitus to assess
      the joint evidence for the association, the influence of individual studies, and
      evidence for publication bias. We searched PubMed, Medline, Embase, Cochrane
      Library, and reference lists of relevant studies to February 2012, and made email
      contact with authors. For the case-control studies, we found 1) support for an
      association between CTLA-4 and type 1 diabetes mellitus, 2) no evidence that this
      association was accounted for by any one study, and 3) no evidence for
      publication bias. In all, although the association between CTLA-4 polymorphisms
      and type 1 diabetes mellitus is weak, we suggest that it is real. Further studies
      are needed to clarify what variant of CTLA-4 (or some related gene) accounts for
      this association. 

PMID- 24085455
TI  - Initial assessment of natural diversity in Mexican fig landraces.
AB  - The common fig (Ficus carica L.) was introduced into Mexico by Spanish Franciscan
      missionaries in the 16th century. It is widely assumed that Mexican figs are the
      Spanish cultivar Black Mission. We collected and propagated 12 fig plants from
      six landraces from different states in Central Mexico that represent different
      climate. All of them were grown in a greenhouse at Universidad Autonoma Chapingo,
      in the State of Mexico. During the experimental period, the greenhouse had an
      average temperature and relative humidity of 29.2 degrees  +/- 5.4 degrees C
      (SEM) and 78.1 +/- 6.7% (SEM), respectively. Morphological characterization was
      done following a selected set of quantitative and qualitative descriptors
      established by the IPGRI. DNA analysis was based on a combination of ISSR and
      RFLP markers. We observed great diversity mainly in fruit weight (28.1-96.2 g),
      fruit shape (ovoid, pyriform), and neck length (0.97-3.80 cm), which could not be
      explained by environmental conditions such as temperature and relative humidity.
      The Nei and Li/Dice similarity coefficient between landraces was determined by
      cluster analysis using the UPGMA method. Based on the morphological
      characterization and DNA fingerprinting data presented in this study, our results
      showed that after hundreds of years, black figs have adapted to local
      environmental condition in Central Mexico, yielding at least six clearly distinct
      landraces that represent valuable and previously undescribed genetic diversity.
      We also suggested names for those landraces according to their location and
      established a basis for further agronomic and molecular characterization of fig
      landraces. 

PMID- 24085456
TI  - Molecular evolution and adaptation of the mitochondrial cytochrome b gene in the
      subgenus Martes.
AB  - Martes species represent a typical example of rapid evolutionary radiation and a
      recent speciation event. To identify regions of the genome that experienced
      adaptive evolution, which might provide clues to their functional importance and
      may be informative about the features that make each species unique, we sought
      evidence of molecular adaptation in the mitochondrial DNA (mtDNA) cytochrome b
      gene in the subgenus Martes. Complete sequences of the cytochrome b gene were
      obtained from 87 samples, including 49 sables, 28 pine martens, and 10 stone
      martens, and were combined with mtDNA sequences of other true martens, such as M.
      melampus and M. americana. Analysis of the cytochrome b gene variation in true
      martens has shown that the evolution of this gene is under negative selection. In
      contrast, positive selection on the cytochrome b protein has been detected by
      means of the software TreeSAAP using a phylogenetic reconstruction of Martes
      taxa. Signatures of adaptive variation in cytochrome b were restricted to the
      transmembrane domains, which likely function as proton pumps. We compared results
      of different methods for testing selection and molecular adaptation, and we
      supposed that the radical changes of the cytochrome b amino acid residues in the
      subgenus Martes may be the result of molecular adaptation to specific
      environmental conditions coupled with species dispersals. 

PMID- 24085457
TI  - An A/G polymorphism rs3746444 in miR-499 is associated with increased cancer
      risk: a meta-analysis.
AB  - An A/G polymorphism (rs3746444) has been identified in the miR-499 gene that can
      change the conformation of the secondary gene structure and thereby directly
      affect binding to target mRNAs and the microRNA (miRNA) maturation process, thus
      altering protein expression and potentially contributing to cancer
      susceptibility. Numerous studies investigating the association between the
      rs3746444 polymorphism and cancers have been published; however, results are
      inconsistent and inconclusive. To clarify the relationship between the miR-499
      rs3746444 polymorphism and cancer, we conducted a comprehensive meta-analysis on
      14 case-control studies comprising 7189 cases and 8577 controls. Odds ratios (OR)
      and 95% confidence intervals (CI) were calculated by using dominant, recessive,
      and co-dominant genetic models. A publication bias test and subgroup analysis
      were also performed. Results showed that the G allele was associated with a
      significantly increased cancer risk compared to the A allele (OR = 1.09; 95%CI =
      1.00-1.18). Similarly, moderately elevated risks were also observed in overall
      analyses in the dominant model (OR = 1.13; 95%CI = 1.01-1.26). Moreover,
      significantly increased risks were observed in Asian populations (G allele vs A
      allele: OR = 1.18; 95%CI = 1.01-1.37; GG vs AA: OR = 1.36; 95%CI = 1.07-1.73;
      dominant model: OR = 1.19; 95%CI = 1.00-1.41; recessive model: OR = 1.31; 95%CI =
      1.03-1.66), but not in European populations. These findings indicate that the miR
      499 rs3746444 polymorphism is associated with an increased cancer risk. 

PMID- 24085459
TI  - [On the situation of permit free self-production of radiopharmaceuticals in
      nuclear medicine].

PMID- 24085458
TI  - [Perfusion brain imaging with SPECT-technique. German Guideline S1].
AB  - This paper describes the guideline for perfusion brain imaging with SPECT
      technique published by the Association of the Scientific Medical Societies in
      Germany (AWMF).The purpose of this guideline is to provide practical assistance
      for indication, examination procedures, findings and their interpretation also
      reflecting the present state of the art. Information and instruction are given
      regarding indication, preparation of the patients and examination procedures of
      brain perfusion SPECT, including preparation and quality control of the tracer as
      well as the radiation dosimetry, technical performance of image acquisition with
      the gamma-camera and image processing. Also advices for interpretation of
      findings are given. In addition, possible pitfalls are described. 

PMID- 24085460
TI  - Extensive peritoneal and pleural lymphomatosis in a patient with Burkitt lymphoma
      revealed with 18F-FDG PET/CT.

PMID- 24085461
TI  - Pre- and intratherapeutical ibritumomab tiuxetan Zevalin(r) dosimetry in
      childhood.

PMID- 24085463
TI  - [Yellow fever: once inoculation is enough].

PMID- 24085462
TI  - Current and historical individual data about exposure of workers in the rayon
      industry to carbon disulfide and their validity in calculating the cumulative
      dose.
AB  - INTRODUCTION: The objective of the study was to investigate how exposure to
      carbon disulfide (CS2) in a rayon-manufacturing plant has changed within two
      decades and whether it is possible to calculate valid data for the individual
      cumulative exposure. METHODS: The data for CS2 concentration in air and
      biological exposure monitoring (2-thio-1,3-thiaxolidine-4-carboxylic acid (TTCA)
      in urine) from two cross-sectional studies, performed in 1992 (n = 362) and 2009
      (n = 212) in a German rayon-manufacturing plant, were compared to data obtained
      from company-internal measurements between the studies. RESULTS: Using the data
      from the cross-sectional studies and company-internal data, cumulative external
      exposure and the cumulative internal exposure were calculated for each worker.
      External and internal CS2 exposure of the employees decreased from 1992 (medians
      4.0 ppm and 1.63 mgTTCA/g creatinine) to 2009 (medians 2.5 ppm and 0.86 mg/g).
      However, company-internal CS2 data do not show a straight trend for this period.
      The annual medians of the company-internal measurement of external exposure to
      CS2 have varied between 2.7 and 8.4 ppm, in which median values exceeded 5 ppm
      generally since 2000. The annual medians for the company-internal biomonitoring
      assessment ranged between 1.2 and 2.8 mg/g creatinine. The cumulative CS2
      exposure ranged from 8.5 to 869.5 ppm years for external exposure and between
      1.30 and 176.2 mg/g creatinine years for the internal exposure. Significant
      correlations were found between the current air pollution and the internal
      exposure in 2009 but also between the cumulative external and internal CS2
      exposure. CONCLUSIONS: Current exposure data, usually collected in cross
      sectional studies, rarely allow a reliable statement on the cumulative dose,
      because of higher exposure in the past and of fluctuating courses of exposure. On
      the other hand, company-internal exposure data may be affected by non
      representative measurement strategies. Some verification of the reliability of
      cumulative exposure data may be possible by testing the correlation between
      cumulative exposure data of external assessment and biological monitoring.

PMID- 24085466
TI  - A prospective randomized study to evaluate the effect of hyaluronic acid sperm
      selection on the intracytoplasmic sperm injection outcome of patients with
      unexplained infertility having normal semen parameters.
AB  - PURPOSE: Sperm quality plays an important role in determining embryo development
      and intracytoplasmic sperm injection (ICSI) outcome. Selection of competent sperm
      based on its ability to bind to hyaluronic acid (HA) has been suggested as one of
      the methods to assess sperm quality. The aim of the present study was to examine
      whether injection of HA bound sperm helps in improving outcome in patients
      undergoing ICSI with unexplained infertility having normal semen parameters.
      METHODS: Patients with unexplained infertility having normal semen parameters in
      accordance with WHO 2010 criterion, undergoing their first IVF-ICSI cycle were
      enrolled during the course of the study.156 patients were prospectively
      randomized after oocyte retrieval and were assigned to either the ICSI group,
      where sperm selection for injection was based on visual assessment, or the PICSI
      group, where sperm were selected based on their ability to bind to HA. Only fresh
      embryo transfers were included in the analysis. RESULTS: There was no difference
      in the fertilization rates, number of top quality embryos and clinical pregnancy
      rates between the ICSI and PICSI groups (65.7 % vs 64.7 %; 45.8 % vs 43.6 % and
      35 % vs 35.2 % respectively). However, a higher pregnancy loss rate was observed
      in the ICSI group (25 % vs 12 %; P = 0.227) as compared to the PICSI group, but
      the difference was not statistically significant. Implantation rates were 22.03 %
      and 18.84 % in the PICSI and ICSI groups respectively. There were 22 (31 %) live
      births in the PICSI group and 21(26.3 %) live births in the ICSI group.
      CONCLUSIONS: Patients with unexplained infertility having normal semen parameters
      may constitute a patient group which does not benefit from this sperm selection
      method. A larger study may be necessary to establish a relationship between PICSI
      and pregnancy loss rate in patients undergoing IVF with unexplained infertility.

PMID- 24085465
TI  - beta-Amyloid-evoked apoptotic cell death is mediated through MKK6-p66shc pathway.
AB  - We have previously shown the involvement of p66shc in mediating apoptosis. Here,
      we demonstrate the novel mechanism of beta-Amyloid-induced toxicity in the
      mammalian cells. beta-Amyloid leads to the phosphorylation of p66shc at the
      serine 36 residue and activates MKK6, by mediating the phosphorylation at serine
      207 residue. Treatment of cells with antioxidants blocks beta-Amyloid-induced
      serine phosphorylation of MKK6, reactive oxygen species (ROS) generation, and
      hence protected cells against beta-Amyloid-induced cell death. Our results
      indicate that serine phosphorylation of p66shc is carried out by active MKK6.
      MKK6 knock-down resulted in decreased serine 36 phosphorylation of p66shc. Co
      immunoprecipitation results demonstrate a direct physical association between
      p66shc and WT MKK6, but not with its mutants. Increase in beta-Amyloid-induced
      ROS production was observed in the presence of MKK6 and p66shc, when compared to
      triple mutant of MKK6 (inactive) and S36 mutant of p66shc. ROS scavengers and
      knock-down against p66shc, and MKK6 significantly decreased the endogenous level
      of active p66shc, ROS production, and cell death. Finally, we show that the MKK6
      p66shc complex mediates beta-Amyloid-evoked apoptotic cell death. 

PMID- 24085467
TI  - Deficits in motor abilities and developmental fractionation of imitation
      performance in high-functioning autism spectrum disorders.
AB  - The co-occurrence of motor and imitation disabilities often characterises the
      spectrum of deficits seen in patients with autism spectrum disorders (ASD).
      Whether these seemingly separate deficits are inter-related and whether, in
      particular, motor deficits contribute to the expression of imitation deficits is
      the topic of the present study and was investigated by comparing these deficits'
      cross-sectional developmental trajectories. To that end, different components of
      motor performance assessed in the Zurich Neuromotor Assessment and imitation
      abilities for facial movements and non-meaningful gestures were tested in 70
      subjects (aged 6-29 years), including 36 patients with high-functioning ASD and
      34 age-matched typically developed (TD) participants. The results show robust
      deficits in probands with ASD in timed motor performance and in the quality of
      movement, which are all independent of age, with one exception. Only
      diadochokinesis improves moderately with increasing age in ASD probands.
      Imitation of facial movements and of non-meaningful hand, finger, hand finger
      gestures not related to social context or tool use is also impaired in ASD
      subjects, but in contrast to motor performance this deficit overall improves with
      age. A general imitation factor, extracted from the highly inter-correlated
      imitation tests, is differentially correlated with components of neuromotor
      performance in ASD and TD participants. By developmentally fractionating
      developmentally stable motor deficits from developmentally dynamic imitation
      deficits, we infer that imitation deficits are primarily cognitive in nature.

PMID- 24085468
TI  - Predictors of posttraumatic stress in parents of children diagnosed with a
      disorder of sex development.
AB  - The aims of the current study were twofold: (1) to assess the prevalence/severity
      of posttraumatic stress symptoms (PTSS) as well as cognitive and emotional
      responses in parents whose children were diagnosed with a disorder of sex
      development (DSD); and (2) to assess factors which contributed to PTSS. We
      hypothesized that parents would show elevated levels of PTSS and that negative
      cognitive and/or emotional responses would be predictive. Participants were
      parents of children diagnosed with a DSD. Thirty-six mothers and 11 fathers
      completed a measure of posttraumatic stress and reported difficulties in the
      domains of cognition (e.g., confusion) and emotion (e.g., grief). Using multiple
      regression, we determined factors contributing to parental PTSS. Reported PTSS
      was high: 31 % of mothers and 18 % of fathers met the threshold for caseness for
      Posttraumatic Stress Disorder. Regression included: child sex, parent sex, child
      age at diagnosis, years since diagnosis, genital ambiguity, father occupation,
      cognitive confusion, and emotional distress. Only cognitive confusion contributed
      significantly to variance in PTSS. Parents of children with DSD may experience
      the diagnosis as traumatic, evidenced by high rates of PTSS in the current
      report. Assessment of reactions to their children's diagnoses revealed that
      cognitive confusion, and not emotional distress, predicted PTSS. In this case,
      direct cognitive interventions may be applicable. Though psychological support is
      widely recommended, no detailed intervention has been offered. Our findings
      suggest that we may directly apply models successful in other areas of
      pediatrics, such as pediatric oncology. Future studies may assess the usefulness
      of such an intervention.

PMID- 24085469
TI  - Functional neuroimaging of sexual arousal: a preliminary meta-analysis comparing
      pedophilic to non-pedophilic men.

PMID- 24085470
TI  - Extensor retinaculum of the wrist: gross anatomical correlation with MR imaging
      after ultrasound-guided tenography with emphasis on anatomical features in wrist
      dorsiflexion responsible for tendon impingement.
AB  - OBJECTIVE: To demonstrate the anatomy of the extensor retinaculum (ER) of the
      wrist using gross anatomical correlation with magnetic resonance (MR) imaging
      before and after ultrasound-guided tenography in four different positions,
      emphasizing the morphological appearance of the ER that occurs with dorsiflexion
      of the wrist to define the nature of extensor tendon impingement in athletes who
      perform repetitive wrist dorsiflexion. MATERIALS AND METHODS: Institutional
      policies were followed regarding cadaver use. Ten upper extremities were
      harvested from fresh cadavers. MR imaging before and after ultrasound-guided
      tenography of the wrist was performed, followed by gross anatomical correlation.
      Two radiologists interpreted the MR images and sections by consensus for the
      anatomical landmarks of the ER, and morphological changes occurring during
      dorsiflexion of the wrist were analyzed and measured. RESULTS: The ER of the
      wrist appeared as a band of low signal intensity on T1- and PD-weighted images.
      Because of its orientation, axial images were best suited to depict the ER
      anatomy; specifically, localization of the bony landmarks and the septal
      attachments. On sagittal images, a consistent appearance of the ER was seen:
      appearing with fusiform morphology in the neutral position, and becoming
      shortened and thickened at the abutment point where the extensor tendons of the
      fourth compartment had a curved excursion during dorsiflexion. The width and
      thickness of the ER in neutral position averaged 13.56 mm and 1.67 mm
      respectively. In wrist dorsiflexion, the average width and thickness changed to
      8.68 mm and 2.15 mm respectively. CONCLUSION: Magnetic resonance imaging is a
      useful technique to demonstrate the ER of the wrist, the septal attachments, and
      morphological changes that occur during dorsiflexion of the wrist, which
      potentially can lead to impingement of the extensor tendons.

PMID- 24085472
TI  - RETRACTION of: Down-regulation of protein tyrosine phosphatase gene expression in
      lactating mouse mammary gland.

PMID- 24085471
TI  - Isolated left ventricular noncompaction: clinical profile and prognosis in 106
      adult patients.
AB  - This study was undertaken to evaluate the clinical course of isolated left
      ventricular noncompaction (ILVNC) and to identify the predictors for adverse
      outcomes in an adult cohort with ILVNC. Between March 2003 and April 2012, 106
      adult patients diagnosed with ILVNC at Fuwai Hospital were included in this
      study. The medical history, electrocardiograms, and echocardiograms of these
      patients were retrospectively analyzed by chart review. Of these patients, 64 (60
      %) were in New York Heart Association (NYHA) functional class III/IV and 84 (79
      %) had systolic dysfunction (left ventricular ejection fraction (LVEF) <50 %).
      During a follow-up of 2.9 +/- 2.1 years, 28 (26 %) patients died or underwent
      heart transplantation. The annual incidence of death or transplantation was 9.1
      %. The determinants of death or heart transplantation included NYHA functional
      class III/IV (hazard ratio (HR) 4.52; 95 % confidence interval (CI) 1.57-13.04; P
      = 0.005), decreased left ventricular ejection fraction (HR 0.94; 95 % CI 0.90
      0.97; P = 0.001), dilated left ventricular end-diastolic diameter (HR, 1.06; 95 %
      CI, 1.02-1.09; P = 0.001), increased left atrial diameter (HR 1.08; 95 % CI 1.03
      1.14; P = 0.001), reduced systolic blood pressure (HR 0.96; 95 % CI 0.94-0.99; P
      = 0.003), the presence of pulmonary hypertension (HR 3.50; 95 % CI 1.63-7.51; P =
      0.001), and right bundle branch block (HR 7.79; 95 % CI 2.56-23.76; P < 0.001).
      In conclusion, this study demonstrates that ILVNC is related to a high incidence
      of death or heart transplantation. Advanced heart failure, a dilated left heart
      with systolic dysfunction, reduced systolic blood pressure, pulmonary
      hypertension, and right bundle branch block predict adverse outcomes of ILVNC.

PMID- 24085473
TI  - Objectively measured sedentary time and its association with physical function in
      older adults.
AB  - The relationship of objectively measured sedentary time (ST), frequency of breaks
      in ST, and lower extremity function (LEF) was investigated in a diverse sample
      aged >= 70 years (n = 217). Physical activity (PA) was assessed by accelerometry
      deriving moderate-vigorous PA (MVPA) minutes per registered hour (MVPA min . hr(
      1)), registered ST (ST min . hr(-1)), and breaks in ST min . hr(-1) (breaks . hr(
      1)). LEF was assessed by the Short Physical Performance Battery. Univariate
      associations with overall LEF were MVPA (r = .523), ST (r = -.499), and breaks (r
      = .389). Adjusted linear regression including MVPA min . hr(-1), ST min . hr(-1),
      and breaks . hr(-1) explained 41.5% of LEF variance. Each additional break . hr(
      1) was associated with 0.58 point increase in LEF. Breaks and MVPA had strongest
      independent associations with LEF. Promoting regular breaks might be useful in
      maintaining or increasing LEF and later life independence. This novel finding is
      important for the design of effective lifestyle interventions targeting older
      adults.

PMID- 24085474
TI  - Positive effect of social work-related values on work outcomes: the moderating
      role of age and work situation.
AB  - OBJECTIVES: This study investigated the effect of social work-related values on
      job performance through job satisfaction and tested whether age and work
      situation would moderate such associations. METHODS: This study consists of two
      parts: Part 1 is a cross-sectional survey among 299 Chinese clerical employees
      aged 19-60 years and Part 2 is a 14-day experience sampling study in a subsample
      of Part 1 (N = 67). RESULTS AND DISCUSSION: Part 1 revealed that age moderated
      the effect of social work-related values on job performance through job
      satisfaction, with a stronger positive effect in older workers than in younger
      workers. Part 2 demonstrated that the moderating effect of age shown in Part 1
      also varied across work situations. In particular, holding momentary social work
      related values was beneficial to the task performance of older workers, and the
      effect was significantly stronger when they were in social situations than in
      nonsocial situations, whereas the effect remained weak among younger workers
      regardless of work context. Moreover, the moderating effect of age could be
      accounted for by future time perspective. This study supports socioemotional
      selectivity theory that goal orientation shifts toward the emphasis of
      interpersonal closeness when one perceives future time as increasingly limited.

PMID- 24085476
TI  - [The Adult Attachment Interview - fundamentals, use, and applications in clinical
      work].
AB  - The present paper looks at the potential of the Adult Attachment Interview (AAI)
      and its underlying basis in attachment theory for use in psychotherapeutic work.
      We summarize the basic tenets of attachment theory, detail the content and
      structure of the AAI, provide instructions for conducting the AAI, and introduce
      the Main et al. (2002) coding system. We then report on associations between AAI
      Attachment groups and psychosomatic diseases and, finally, demonstrate
      applications of the AAI in clinical work and research. 

PMID- 24085475
TI  - Characterization of genotype IX Newcastle disease virus strains isolated from
      wild birds in the northern Qinling Mountains, China.
AB  - This study was conducted to evaluate the virulence and evolution of genotype IX
      Newcastle disease virus (NDV) isolates obtained from wild birds in the northern
      Qinling Mountains of China. Five isolates were obtained from 374 larynx and
      cloacae swabs, which were collected from multiple asymptomatic wild bird species
      from August 2008 to July 2011, and were subsequently characterized by pathotype
      and genotype. Deduced amino acid sequences revealed that all five NDV isolates
      exhibited velogenic fusion protein cleavage sites motif (112)R-R-Q-R-R-F(117),
      shared as high as 99.8-99.9 % homology with each other, and varied in pathotype
      by intracerebral pathogenicity indices (ICPI) of 0.425-1.638. Phylogenetic
      analysis showed that all five isolates were clustered to genotype IX NDV. This is
      the first study to confirm multiple asymptomatic wild bird species as natural
      carriers of virulent genotype IX NDV. A novel NDV isolate from the Spotted-necked
      Dove (family Columbidae) exhibited discordance between its lentogenic ICPI and
      its virulent proteolytic cleavage site motif (112)R-R-Q-R-R-F(117). Although the
      five isolates underwent several amino acid mutations in the fusion protein,
      evidence of continuous evolutionary divergence did exist in the genotype IX NDV,
      which was always regarded as a conservative genotype.

PMID- 24085477
TI  - [Depressives have the better view - the influence of mood on the recognition of
      emotional expression].
AB  - OBJECTIVES: There are different approaches to whether depressed people perceive
      their environment differently than nondepressed.We analyzed whether depressed
      patients show greater deficits in decoding emotional expressions than
      nondepressives. METHODS: A sample of 52 depressed patients and a sample of 72
      nondepressed persons were investigated as to their ability to identify
      emotionally laden facial expressions (computer-assisted presentation of photos).
      RESULTS: Our results demonstrate significant differences between depressive
      patients and nondepressive persons in the ability to decode the emotional states
      of others. In four out of six tests the depressive persons achieved significantly
      better results. CONCLUSIONS: We suggest that these results can be interpreted as
      further evidence for the concept of depressive emotional realism.

PMID- 24085478
TI  - [Psychosomatic and psychotherapeutic outpatient care in Germany - Capacity
      profile based on data from the National Association of Statutory Health Insurance
      Physicians].
AB  - OBJECTIVES: At the centre of the study lay a representation of outpatient
      psychosomatic and psychotherapeutic care with a focus on different groups of
      medical and psychological therapists. METHODS: The routine data of the National
      Association of Statutory Health Insurance Physicians (KBV) from the year 2008
      were analyzed based on a systematic literature review (Medline, ISI, to November
      2010). RESULTS: Neurologists and psychiatrists see the most patients (n = 3,172
      vs n = 1,347 cases per practice), but they rarely provide services according to
      the directives for psychotherapy (4,4 %). However, specialists for psychosomatic
      medicine and psychotherapy (65 %), physicians providing only psychotherapy (66 %)
      and psychological psychotherapists (73 %) provide care mainly according to the
      directives for psychotherapy and therefore see fewer patients (170-190 cases per
      practice).Medical psychotherapists work more often on a psychodynamic basis,
      while psychological psychotherapists perform more often behavioral therapy.
      CONCLUSIONS: The treatment of patients with mental and psychosomatic disorders is
      based on three columns of care, which differ in their supply profile and each
      make a specific contribution to the treatment.

PMID- 24085479
TI  - [The influence of patient- and treatment-related factors on the success of
      inpatient psychotherapy].
AB  - OBJECTIVES: This study investigates the symptomatic and interpersonal efficacy of
      inpatient psychodynamic psychotherapy as well as the influence of several patient
      and treatment-related factors on the success of psychotherapy. METHODS: In this
      naturalistic study, 715 patients were assessed with the Symptom Checklist (SCL-90
      R) and the Inventory of Interpersonal Problems (IIP). The influence of several
      patient-and treatment-related factors on the success of psychotherapy was
      analyzed using logistic regression. RESULTS: Patients improved significantly on
      all SCL-90-R and IIP scales. The patients' attachment style, ICD-10 diagnosis,
      and motivation for therapy, as well as additionally job situation for the
      symptomatic outcome and additionally age for the interpersonal outcome, were
      significant predictors of therapeutic success. CONCLUSIONS: Patients with a
      secure attachment style, a diagnosis of depression, and a high motivation for
      therapy are more likely to experience therapeutic success than other patients.
      Furthermore, regular occupational activity has a positive effect on symptomatic
      treatment outcome, while a younger age has a positive effect on interpersonal
      treatment outcome.

PMID- 24085480
TI  - [A longitudinal analysis of the inpatient treatment of the elderly in
      psychosomatic departments].
AB  - OBJECTIVES: This article investigates the development of the inpatient treatment
      capabilities of older patients from the age of 50 onward in inpatient
      psychosomatic-psychotherapeutic departments over a period of 15 years. METHOD: A
      Germany-wide postal survey that was almost identical to two previously conducted
      cross-sectional surveys (Lange et al. 1995; Wenker 2010) was sent to
      psychosomatic-psychotherapeutic departments. This survey collected data on the
      status and concept of the department as well as on the number of patients, number
      of elderly people, programs for elderly people, and future concepts of the
      departments. RESULTS: The response of psychosomatic departments was higher than
      in previous years. The forms of therapy used differ between the individual clinic
      subtypes. The programs for elderly people remained constant, as did the special
      qualification measures for employees. Proportionally more elderly patients from
      the age of 50 onward were treated in psychosomatic clinics and departments, two
      thirds of whom were women. DISCUSSION: The survey revealed that psychosomatic
      psychotherapeutic therapies for the treatment of elderly people increased over
      the last year. With regard to the demographic change and the future receptiveness
      of elderly people to psychotherapy, the inpatient sector seems to be prepared for
      the rising numbers of elderly people. How large the lack of therapy capacity
      needed for inpatient psychosomatic-psychotherapeutic treatment will be cannot be
      answered by this survey.

PMID- 24085481
TI  - [The neuropsychological principles of psychotherapy].
AB  - Recent advances achieved in the field of clinical neuro(bio-)psychology have been
      varied and impressive. Together with the related social and psychosocial aspects,
      they contribute to and enrich the development of new options in diagnosis and
      psychotherapy. Important research results are discussed here based on the
      examples of depression, Alzheimer's disease and self-injury, which profit greatly
      from neuropsychological research, especially through early detection of symptoms
      and prevention. 

PMID- 24085483
TI  - Role of tissue transglutaminase and effect of cantharidinate in human colorectal
      cancer.
AB  - The role of tissue transglutaminase (tTG) in cancer development remains an
      important field of study. The aim of the current study was to understand the
      involvement of tTG in cancer and the inhibitory effect of cantharidinate on the
      expression of tTG in human colorectal cancer (CRC) using immunohistochemical and
      PCR analysis. The results showed that the expression of tTG increased in human
      CRC and cantharidinate inhibited the expression of tTG. These results suggested
      that tTG is significant in human CRC and that tTG may be an important target for
      tumor chemoprevention and treatment. Cantharidinate may be considered as a novel
      co-therapy for controlling tTG expression in human CRC.

PMID- 24085482
TI  - Learning from halophytes: physiological basis and strategies to improve abiotic
      stress tolerance in crops.
AB  - BACKGROUND: Global annual losses in agricultural production from salt-affected
      land are in excess of US$12 billion and rising. At the same time, a significant
      amount of arable land is becoming lost to urban sprawl, forcing agricultural
      production into marginal areas. Consequently, there is a need for a major
      breakthrough in crop breeding for salinity tolerance. Given the limited range of
      genetic diversity in this trait within traditional crops, stress tolerance genes
      and mechanisms must be identified in extremophiles and then introduced into
      traditional crops. SCOPE AND CONCLUSIONS: This review argues that learning from
      halophytes may be a promising way of achieving this goal. The paper is focused
      around two central questions: what are the key physiological mechanisms
      conferring salinity tolerance in halophytes that can be introduced into non
      halophyte crop species to improve their performance under saline conditions and
      what specific genes need to be targeted to achieve this goal? The specific traits
      that are discussed and advocated include: manipulation of trichome shape, size
      and density to enable their use for external Na(+) sequestration; increasing the
      efficiency of internal Na(+) sequestration in vacuoles by the orchestrated
      regulation of tonoplast NHX exchangers and slow and fast vacuolar channels,
      combined with greater cytosolic K(+) retention; controlling stomata aperture and
      optimizing water use efficiency by reducing stomatal density; and efficient
      control of xylem ion loading, enabling rapid shoot osmotic adjustment while
      preventing prolonged Na(+) transport to the shoot.

PMID- 24085484
TI  - Half-marathon running performance is not improved by a rate of fluid intake above
      that dictated by thirst sensation in trained distance runners.
AB  - PURPOSE: It has been demonstrated that exercise-induced dehydration (EID) does
      not impair, and ad libitum drinking optimizes, cycling time-trial (TT)
      performance. However, the idea that EID >= 2 % bodyweight (BW) impairs endurance
      performance is well ingrained. No study has tested the impact of EID upon running
      TT performance. We compared the effects of thirst-driven (TD) vs. programmed
      fluid intake (PFI) aimed at maintaining EID-associated BW loss <2 % on half
      marathon performance. METHODS: Ten trained distance runners underwent, in a
      randomized, crossover fashion, two, 21.1 km running TTs on a treadmill (30 
      degrees C, 42 % relative humidity) while facing a wind speed matching running
      speed and drinking water (1) according to thirst sensation (TD) or (2) to
      maintain BW loss <2 % of their pre-exercise BW (PFI), as recommended by the
      American College of Sports Medicine. RESULTS: Despite that PFI significantly
      reduced EID from 3.1 +/- 0.6 (TD) to 1.3 +/- 0.7 % BW (PFI), mean rectal
      temperature from 39.4 +/- 0.4 to 39.1 +/- 0.3  degrees C, mean body temperature
      from 38.1 +/- 0.4 to 37.7 +/- 0.2  degrees C and mean heart rate from 175 +/- 9
      to 171 +/- 8 bpm, neither half-marathon time (TD 89.8 +/- 7.7; PFI 89.6 +/- 7.7
      min) nor running pace (TD 4.3 +/- 0.4; PFI 4.2 +/- 0.4 min/km) differed
      significantly between trials. CONCLUSION: Albeit providing trivial cardiovascular
      and thermoregulatory advantages, in trained distance runners, PFI (1,380 +/- 320
      mL/h) offers no performance benefits over TD fluid intake (384 +/- 180 mL/h)
      during a half-marathon raced under warm conditions.

PMID- 24085485
TI  - The effect of an even-pacing strategy on exercise tolerance in well-trained
      cyclists.
AB  - PURPOSE: Previous research has suggested that the optimal pacing strategy for
      self-paced exercise lasting >4 min is a uniform distribution of work, but this
      posit is not well established for prolonged endurance events. This study examined
      the utility of even pacing during 20 km cycling time trials (TTs). METHODS:
      Fifteen well-trained male cyclists ([Formula: see text]O2max = 4.80 +/- 0.38 L
      min(-1)) completed three best effort self-paced (SP) simulated 20 km TTs,
      followed by two even-paced trials. In one even-paced trial, participants cycled
      to exhaustion (EPtlim) at a fixed intensity equivalent to their best SP
      performance. In the other EP trial, participants were instructed to maintain this
      target intensity for a distance of 20 km, but the actual intensity was free to
      vary depending on the effort and cadence of the cyclist (EP-maintained).
      Cardiorespiratory, blood lactate and perceptual (RPE and affect) measures were
      assessed throughout. RESULTS: Nine out of fifteen cyclists failed the EPtlim
      task, completing 51-83 % (10.3-15.3 km) of the work done in their SP trial.
      Failure as a result of even pacing was associated with a faster rise in blood
      lactate, attainment of a higher relative intensity during SP and a moderate fast
      starting strategy. This failure was independent of the nature of the even-paced
      task. CONCLUSION: By adopting an uneven, parabolic distribution of work, cyclists
      in this study were able to achieve an average intensity during self-paced
      exercise in excess of their maximum sustainable power output. A subsequent
      matched even-paced bout resulted in cumulative metabolic stress that could not be
      managed by moment-to-moment changes in power output. These results challenge the
      notion that strict even pacing is optimal for endurance time trial events.

PMID- 24085486
TI  - Pharmacokinetics and hepatic uptake of gliquidone affected by Huangqi injection.
AB  - The root of Astragalus membranaceus also known as Huang Qi in China is a common
      traditional Chinese herb with extensive pharmacological activities. Huangqi
      injection (HI), a common preparation of Huang Qi, was wildly co-administered with
      gliquidone to treat diabetes mellitus and diabetic nephropathy in clinic of
      China. The aim of the study was to investigate the effect of HI on the
      pharmacokinetics and hepatic uptake of gliquidone and related mechanism to ensure
      the safety and efficacy of their usage. Normal rats (n = 5) and streptozotocin
      (STZ)-induced diabetic rats (n = 5) were administered orally with 120 mg/kg
      gliquidone alone or in combination with 8 ml/kg HI (i.v.), HI was given
      intravenously 5 min before that of gliquidone. The plasma concentration of
      gliquidone was determined by HPLC-fluorescence. In addition, hepatic uptake of
      gliquidone with or without HI was evaluated in fresh primary rat hepatocytes. Co
      administration of HI with gliquidone could significantly increased the
      bioavailability of gliquidone in normal and STZ-induced diabetic rats (n = 5);
      the concentration of gliquidone in fresh primary rat hepatocytes was greatly
      decreased by HI. This study suggested that when HI and gliquidone co
      administering to normal and diabetic rats, the pharmacokinetics of gliquidone was
      greatly changed, and these changes connect with HI inhibiting hepatic uptake of
      gliquidone, and transportation of gliquidone across liver mucosal membrane
      inhibited by HI would be the main mechanisms. 

PMID- 24085487
TI  - Information processing in the mirror neuron system in primates and machines.
AB  - The mirror neuron system in primates matches observations of actions with the
      motor representations used for their execution, and is a topic of intense
      research and debate in biological and computational disciplines. In robotics,
      models of this system have been used for enabling robots to imitate and learn how
      to perform tasks from human demonstrations. Yet, existing computational and
      robotic models of these systems are found in multiple levels of description, and
      although some models offer plausible explanations and testable predictions, the
      difference in the granularity of the experimental setups, methodologies,
      computational structures and selected modeled data make principled meta-analyses,
      common in other fields, difficult. In this paper, we adopt an interdisciplinary
      approach, using the BODB integrated environment in order to bring together
      several different but complementary computational models, by functionally
      decomposing them into brain operating principles (BOPs) which each capture a
      limited subset of the model's functionality. We then explore links from these
      BOPs to neuroimaging and neurophysiological data in order to pinpoint
      complementary and conflicting explanations and compare predictions against
      selected sets of neurobiological data. The results of this comparison are used to
      interpret mirror system neuroimaging results in terms of neural network activity,
      evaluate the biological plausibility of mirror system models, and suggest new
      experiments that can shed light on the neural basis of mirror systems. 

PMID- 24085489
TI  - Short-term synaptic plasticity and the 'active calcium' hypothesis at a central
      synapse.

PMID- 24085488
TI  - Specificity of a protein-protein interface: local dynamics direct substrate
      recognition of effector caspases.
AB  - Proteases are prototypes of multispecific protein-protein interfaces. Proteases
      recognize and cleave protein and peptide substrates at a well-defined position in
      a substrate binding groove and a plethora of experimental techniques provide
      insights into their substrate recognition. We investigate the caspase family of
      cysteine proteases playing a key role in programmed cell death and inflammation,
      turning caspases into interesting drug targets. Specific ligand binding to one
      particular caspase is difficult to achieve, as substrate specificities of caspase
      isoforms are highly similar. In an effort to rationalize substrate specificity of
      two closely related caspases, we investigate the substrate promiscuity of the
      effector Caspases 3 and 7 by data mining (cleavage entropy) and by molecular
      dynamics simulations. We find a strong correlation between binding site rigidity
      and substrate readout for individual caspase subpockets explaining more stringent
      substrate readout of Caspase 7 via its narrower conformational space. Caspase 3
      subpockets S3 and S4 show elevated local flexibility explaining the more
      unspecific substrate readout of that isoform in comparison to Caspase 7. We show
      by in silico exchange mutations in the S3 pocket of the proteases that a proline
      residue in Caspase 7 contributes to the narrowed conformational space of the
      binding site. These findings explain the substrate specificities of caspases via
      a mechanism of conformational selection and highlight the crucial importance of
      binding site local dynamics in substrate recognition of proteases. Proteins 2014;
      82:546-555. (c) 2013 Wiley Periodicals, Inc. 

PMID- 24085490
TI  - Preformed vs. on-demand: molecular economics of endocannabinoid signalling.

PMID- 24085491
TI  - A passive cable to excite oligodendrocyte precursor glia.

PMID- 24085492
TI  - Which molecules regulate synaptic brain asymmetries?

PMID- 24085493
TI  - A road map for a tissue engineering concept for restoring structure and function
      after limb loss.

PMID- 24085494
TI  - Scout view in pediatric CT neuroradiological evaluation: do not underestimate!
AB  - PURPOSE: Computed tomography (CT) is an important first-line imaging tool in
      pediatric neuroradiology. The scout view (SV) is essential for planning the CT
      study. It is frequently underestimated for its diagnostic value but may harbor
      important diagnostic clues. We present and discuss the role of SV in the accurate
      interpretation of pediatric neuroradiological CT studies. METHODS: CT studies
      have been collected over 12 months by an experienced pediatric neuroradiologist.
      Retrospective evaluation of SV and axial CT images was performed in nine
      children, where the SV gave important diagnostic information. Abnormalities on SV
      were classified as (1) located outside the field of view as imaged by the cross
      sectional CT slices or (2) located in the plane of the cross-sectional CT slices
      or orthogonal to it. RESULTS: Five male and four female patients were included.
      The mean age at CT was 9.86 years (range, 0.75 to 19 years). Abnormalities on SV
      were located outside of the field of view as imaged by cross-sectional CT slices
      in six out of nine children and were within the plane of the CT slices or
      orthogonal to it in three out of nine children. CONCLUSIONS: A thorough and
      accurate evaluation of the SV may add valuable, clinically relevant information
      and should be a routine part of the interpretation of each pediatric
      neuroradiological CT study.

PMID- 24085495
TI  - Third ventriculostomy site as a neuroreceptorial area.
AB  - PURPOSE: Endoscopic third ventriculostomy is an established method for treating
      hydrocephalus. The third ventriculostomy site is considered a safe area that can
      be disrupted during surgical endoscopic procedures. The question of the clinical
      consequences of an apparently unavoidable injury to the floor of the third
      ventricle has been sporadically addressed in the literature. The aim of this
      study is to describe our anatomical and operative findings during endoscopic
      procedures performed in fluorescent mode after intravenous fluorescein injection
      and address the possible role of fluorescein-enhanced visualization of the median
      eminence as an accessory tool in order to partially spare this functional
      structure when performing ventriculostomy. METHODS: We prospectively administered
      intravenously 500 mg of fluorescein sodium in 12 consecutive endoscopic surgery
      cases. A flexible scope equipped with dual observation modes for both white light
      and fluorescence was used. Taking into account the position of the basilar apex
      and the need for a conveniently sized stoma, a perforation area was chosen and
      dilated using a Fogarty balloon, guided by fluorescein-enhanced visualization of
      the median eminence. RESULTS: After a mean of 20 s in the fluorescent mode, the
      fluorescein enhanced the visualization of the median eminence-tuber cinereum
      complex. In our preliminary experience, by opening the stoma in the fluorescence
      mode, almost half of the visible median eminence surface can be spared from
      iatrogenic sacrifice. CONCLUSIONS: Tailoring fluorescence-guided ventriculostomy
      is a feasible way of trying to preserve the median eminence and may have
      implications for the site and safety of this common surgical procedure.

PMID- 24085496
TI  - Chinese Society for Pediatric Neurosurgery (CSPN): a new society promoting
      pediatric neurosurgery in China.
AB  - The China Pediatric Neurosurgery Forum (CPNF) 2013 was held from June 21 to June
      23 in Shanghai, a major financial center and a global influential city of China.
      The aim of the meeting is to establish the Chinese Society for Pediatric
      Neurosurgery (CSPN). The meeting was organized by the Chinese Medical Association
      comprising the Chairman of the Neurosurgery Department of the Chinese Medical
      Association Dr. Zhou, Dingbiao; the International Society for Pediatric
      Neurosurgery (ISPN) Education Committee chaired by Dr. Gianpiero Tamburrini,
      member of the World Federation of Neurosurgical Societies (WFNS) Pediatric
      Neurosurgery Committee; and ISPN Education Committee member Dr. Ma Jie. 

PMID- 24085497
TI  - A sibling-comparison study of smoking during pregnancy and childhood
      psychological traits.
AB  - Prenatal exposure to substances of abuse is associated with numerous
      psychological problems in offspring, but quasi-experimental studies controlling
      for co-occurring risk factors suggest that familial factors (e.g., genetic and
      environmental effects shared among siblings) confound many associations with
      maternal smoking during pregnancy (SDP). Few of the quasi-experimental studies in
      this area have explored normative psychological traits in early childhood or
      developmental changes across the lifespan, however. The current study used
      multilevel growth curve models with a large, nationally-representative sample in
      the United States to investigate for potential effects of SDP on the
      developmental trajectories of cognitive functioning, temperament/personality, and
      disruptive behavior across childhood, while accounting for shared familial
      confounds by comparing differentially exposed siblings and statistically
      controlling for offspring-specific covariates. Maternal SDP predicted the
      intercept (but not change over time) for all cognitive and externalizing
      outcomes. Accounting for familial confounds, however, attenuated the association
      between SDP exposure and all outcomes, except the intercept (age 5) for reading
      recognition. These findings, which are commensurate with previous quasi
      experimental research on more severe indices of adolescent and adult problems,
      suggest that the associations between SDP and developmental traits in childhood
      are due primarily to confounding factors and not a causal association.

PMID- 24085498
TI  - In vitro evaluation of caffeoyl and cinnamoyl derivatives as potential prolyl
      oligopeptidase inhibitors.
AB  - A screening of the natural product chlorogenic acid, isolated from the Brazilian
      medicinal plant Hypericum brasiliense, caffeic acid, cinnamic acid, and p
      methoxycinnamic acid, and derivatives of caffeoylquinic, caffeoyl, and cinnamoyl
      against the enzymes prolyl oligopeptidase and dipeptidyl peptidase IV was carried
      out. Caffeoylquinic, caffeoyl, and cinnamoyl derivatives were prepared using
      simple derivatization procedures and through coupling reactions with the amino
      acid proline. The dipeptidyl peptidase IV assay showed inhibitory activity of the
      tested compounds at a high concentration (500 uM) in the range of 81.5-7.2 %. In
      contrast, the derivatives methyl ester and 1,7-acetonide obtained from
      chlorogenic acid, and caffeic acid and its methyl ester derivative showed
      selectivity and activity as prolyl oligopeptidase inhibitors, with IC50 values of
      3 to 14 mM. 

PMID- 24085500
TI  - Breast cancer detection using high-resolution breast PET compared to whole-body
      PET or PET/CT.
AB  - PURPOSE: To compare the performance characteristics of positron emission
      mammography (PEM) with those of whole-body PET (WBPET) and PET/CT in women with
      newly diagnosed breast cancer. METHODS: A total of 178 women consented to PEM for
      presurgical planning in an IRB-approved protocol and also underwent either WBPET
      (n = 69) or PET/CT (n = 109) imaging, as per usual care at three centers. Tumor
      detection sensitivity, positive predictive values, and (18)F-fluorodeoxyglucose
      (FDG) uptake were compared between the modalities. The effects of tumor size,
      type, and grade on detection were examined. The chi-squared or Fisher's exact
      tests were used to compare distributions between groups, and McNemar's test was
      used to compare distributions for paired data within subject groups, i.e. PEM
      versus WBPET or PEM versus PET/CT. RESULTS: The mean age of the women was 59 +/-
      12 years (median 60 years, range 26-89 years), with a mean invasive index tumor
      size of 1.6 +/- 0.8 cm (median 1.5 cm, range 0.5-4.0 cm). PEM detected more index
      tumors (61/66, 92%) than WBPET (37/66, 56%; p < 0.001) or PET/CT (95/109, 87% vs.
      104/109, 95% for PEM; p < 0.029). Sensitivity for the detection of additional
      ipsilateral malignancies was also greater with PEM (7/15, 47%) than with WBPET
      (1/15, 6.7%; p = 0.014) or PET/CT (3/23, 13% vs. 13/23, 57% for PEM; p = 0.003).
      Index tumor detection decreased with decreasing invasive tumor size for both
      WBPET (p = 0.002) and PET/CT (p < 0.001); PEM was not significantly affected (p =
      0.20). FDG uptake, quantified in terms of maximum PEM uptake value, was lowest in
      ductal carcinoma in situ (median 1.5, range 0.7-3.0) and invasive lobular
      carcinoma (median 1.5, range 0.7-3.4), and highest in grade III invasive ductal
      carcinoma (median 3.1, range 1.4-12.9). CONCLUSION: PEM was more sensitive than
      either WBPET or PET/CT in showing index and additional ipsilateral breast tumors
      and remained highly sensitive for tumors smaller than 1 cm.

PMID- 24085499
TI  - The EANM and SNMMI practice guideline for lymphoscintigraphy and sentinel node
      localization in breast cancer.
AB  - PURPOSE: The accurate harvesting of a sentinel node in breast cancer includes a
      sequence of procedures with components from different medical specialities,
      including nuclear medicine, radiology, surgical oncology and pathology. The aim
      of this document is to provide general information about sentinel lymph node
      detection in breast cancer patients. METHODS: The Society of Nuclear Medicine and
      Molecular Imaging (SNMMI) and the European Association of Nuclear Medicine (EANM)
      have written and approved these guidelines to promote the use of nuclear medicine
      procedures with high quality. The final result has been discussed by
      distinguished experts from the EANM Oncology Committee, the SNMMI and the
      European Society of Surgical Oncology (ESSO). CONCLUSION: The present guidelines
      for nuclear medicine practitioners offer assistance in optimizing the diagnostic
      information from the SLN procedure. These guidelines describe protocols currently
      used routinely, but do not include all existing procedures. They should therefore
      not be taken as exclusive of other nuclear medicine modalities that can be used
      to obtain comparable results. It is important to remember that the resources and
      facilities available for patient care may vary.

PMID- 24085501
TI  - Somatostatin-based radiopeptide therapy with [177Lu-DOTA]-TOC versus [90Y-DOTA]
      TOC in neuroendocrine tumours.
AB  - PURPOSE: Somatostatin-based radiopeptide treatment is generally performed using
      the beta-emitting radionuclides (90)Y or (177)Lu. The present study aimed at
      comparing benefits and harms of both therapeutic approaches. METHODS: In a
      comparative cohort study, patients with advanced neuroendocrine tumours underwent
      repeated cycles of [(90)Y-DOTA]-TOC or [(177)Lu-DOTA]-TOC until progression of
      disease or permanent adverse events. Multivariable Cox regression and competing
      risks regression were employed to examine predictors of survival and adverse
      events for both treatment groups. RESULTS: Overall, 910 patients underwent 1,804
      cycles of [(90)Y-DOTA]-TOC and 141 patients underwent 259 cycles of [(177)Lu
      DOTA]-TOC. The median survival after [(177)Lu-DOTA]-TOC and after [(90)Y-DOTA]
      TOC was comparable (45.5 months versus 35.9 months, hazard ratio 0.91, 95%
      confidence interval 0.63-1.30, p = 0.49). Subgroup analyses revealed a
      significantly longer survival for [(177)Lu-DOTA]-TOC over [(90)Y-DOTA]-TOC in
      patients with low tumour uptake, solitary lesions and extra-hepatic lesions. The
      rate of severe transient haematotoxicities was lower after [(177)Lu-DOTA]-TOC
      treatment (1.4 vs 10.1%, p = 0.001), while the rate of severe permanent renal
      toxicities was similar in both treatment groups (9.2 vs 7.8%, p = 0.32).
      CONCLUSION: The present results revealed no difference in median overall survival
      after [(177)Lu-DOTA]-TOC and [(90)Y-DOTA]-TOC. Furthermore, [(177)Lu-DOTA]-TOC
      was less haematotoxic than [(90)Y-DOTA]-TOC.

PMID- 24085502
TI  - Evaluation of the PET component of simultaneous [(18)F]choline PET/MRI in
      prostate cancer: comparison with [(18)F]choline PET/CT.
AB  - PURPOSE: The aim of this study was to evaluate the positron emission tomography
      (PET) component of [(18)F]choline PET/MRI and compare it with the PET component
      of [(18)F]choline PET/CT in patients with histologically proven prostate cancer
      and suspected recurrent prostate cancer. METHODS: Thirty-six patients were
      examined with simultaneous [(18)F]choline PET/MRI following combined
      [(18)F]choline PET/CT. Fifty-eight PET-positive lesions in PET/CT and PET/MRI
      were evaluated by measuring the maximum and mean standardized uptake values
      (SUVmax and SUVmean) using volume of interest (VOI) analysis. A scoring system
      was applied to determine the quality of the PET images of both PET/CT and
      PET/MRI. Agreement between PET/CT and PET/MRI regarding SUVmax and SUVmean was
      tested using Pearson's product-moment correlation and Bland-Altman analysis.
      RESULTS: All PET-positive lesions that were visible on PET/CT were also
      detectable on PET/MRI. The quality of the PET images was comparable in both
      groups. Median SUVmax and SUVmean of all lesions were significantly lower in
      PET/MRI than in PET/CT (5.2 vs 6.1, p<0.05 and 2.0 vs 2.6, p<0.001,
      respectively). Pearson's product-moment correlation indicated highly significant
      correlations between SUVmax of PET/CT and PET/MRI (R=0.86, p<0.001) as well as
      between SUVmean of PET/CT and PET/MRI (R=0.81, p<0.001). Bland-Altman analysis
      revealed lower and upper limits of agreement of -2.77 to 3.64 between SUVmax of
      PET/CT vs PET/MRI and -1.12 to +2.23 between SUVmean of PET/CT vs PET/MRI.
      CONCLUSION: PET image quality of PET/MRI was comparable to that of PET/CT. A
      highly significant correlation between SUVmax and SUVmean was found. Both SUVmax
      and SUVmean were significantly lower in [(18)F]choline PET/MRI than in
      [(18)F]choline PET/CT. Differences of SUVmax and SUVmean might be caused by
      different techniques of attenuation correction. Furthermore, differences in
      biodistribution and biokinetics of [(18)F]choline between the subsequent
      examinations and in the respective organ systems have to be taken into account.

PMID- 24085503
TI  - [18F]Flutemetamol amyloid-beta PET imaging compared with [11C]PIB across the
      spectrum of Alzheimer's disease.
AB  - PURPOSE: The aim was to identify the amyloid beta (Abeta) deposition by positron
      emission tomography (PET) imaging with the (18)F-labeled Pittsburgh compound B
      (PIB) derivative [(18)F]flutemetamol (FMM) across a spectrum of Alzheimer's
      disease (AD) and to compare Abeta deposition between [(18)F]FMM and [(11)C]PIB
      PET imaging. METHODS: The study included 36 patients with AD, 68 subjects with
      mild cognitive impairment (MCI), 41 older healthy controls (HC) (aged >=56), 11
      young HC (aged <=45), and 10 transitional HC (aged 46-55). All 166 subjects
      underwent 30-min static [(18)F]FMM PET 85 min after injection, 60-min dynamic
      [(11)C]PIB PET, and cognitive testing. [(18)F]FMM scans were assessed visually,
      and standardized uptake value ratios (SUVR) were defined quantitatively in
      regions of interest identified on coregistered MRI (cerebellar cortex as a
      reference region). The PIB distribution volume ratios (DVR) were determined in
      the same regions. RESULTS: Of 36 AD patients, 35 had positive scans, while 36 of
      41 older HC subjects had negative scans. [(18)F]FMM scans had a sensitivity of
      97.2% and specificity of 85.3% in distinguishing AD patients from older HC
      subjects, and a specificity of 100% for young and transitional HC subjects. The
      [(11)C]PIB scan had the same results. Interreader agreement was excellent (kappa
      score = 0.81). The cortical FMM SUVR in AD patients was significantly greater
      than in older HC subjects (1.76 +/- 0.23 vs 1.30 +/- 0.26, p < 0.01). Of the MCI
      patients, 68 had a bimodal distribution of SUVR, and 29 of them (42.6%) had
      positive scans. Cortical FMM SUVR values were strongly correlated with PIB DVR (r
      = 0.94, n = 145, p < 0.001). CONCLUSION: [(18)F]FMM PET imaging detects Abeta
      deposition in patients along the continuum from normal cognitive status to
      dementia of AD and discriminates AD patients from HC subjects, similar to
      [(11)C]PIB PET.

PMID- 24085504
TI  - Quantitative assessment of global lung inflammation following radiation therapy
      using FDG PET/CT: a pilot study.
AB  - PURPOSE: Radiation pneumonitis is the most severe dose-limiting complication in
      patients receiving thoracic radiation therapy. The aim of this study was to
      quantify global lung inflammation following radiation therapy using FDG PET/CT.
      METHODS: We studied 20 subjects with stage III non-small-cell lung carcinoma who
      had undergone FDG PET/CT imaging before and after radiation therapy. On all
      PET/CT studies, the sectional lung volume (sLV) of each lung was calculated from
      each slice by multiplying the lung area by slice thickness. The sectional lung
      glycolysis (sLG) was calculated by multiplying the sLV and the lung sectional
      mean standardized uptake value (sSUVmean) on each slice passing through the lung.
      The lung volume (LV) was calculated by adding all sLVs from the lung, and the
      global lung glycolysis (GLG) was calculated by adding all sLGs from the lung.
      Finally, the lung SUVmean was calculated by dividing the GLG by the LV. The
      amount of inflammation in the lung parenchyma directly receiving radiation
      therapy was calculated by subtracting tumor measurements from GLG. RESULTS: In
      the lung directly receiving radiation therapy, the lung parenchyma SUVmean and
      global lung parenchymal glycolysis were significantly increased following
      therapy. In the contralateral lung (internal control), no significant changes
      were observed in lung SUVmean or GLG following radiation therapy. CONCLUSION:
      Global lung parenchymal glycolysis and lung parenchymal SUVmean may serve as
      potentially useful biomarkers to quantify lung inflammation on FDG PET/CT
      following thoracic radiation therapy.

PMID- 24085505
TI  - Bacteria recovered from a high-altitude, tropical glacier in Venezuelan Andes.
AB  - Glacial-ice microorganisms are intensively studied world-wide for a number of
      reasons, including their psychrophilic lifestyle, their usefulness in
      biotechnology procedures and their relationship with the search of life outside
      our planet. However, because of the difficulties for accessing and working at
      altitudes of >5.000 m above sea level, tropical glaciers have received much less
      attention than their arctic and antarctic counterparts. In the present work we
      isolated and characterized a total of forty-five pure isolates originating from
      direct plating of melted ice collected at the base of a rapidly-retreating, small
      glacier located at around 4.900 m.a.s.l. in Mount Humboldt (Sierra Nevada
      National Park, Merida State, Venezuela). Initial examination of melted ice showed
      the presence of abundant- (>106 cells ml-1), morphologically diverse- and active
      bacterial cells, many of which were very small ("dwarf cells"). The majority of
      the isolates were psychrophilic or psychrotolerant and many produced and excreted
      cold-active extracellular enzymes (proteases and amylases). The antibiotic tests
      showed an elevated percentage of isolates resistant to high doses (100 MUg/ml) of
      different antibiotics including ampicillin, penicillin, nalidixic acid,
      streptomycin, chloramphenicol, kanamycin and tetracycline. Multiresistance was
      also observed, with 22.22 % of the strains simultaneously resistant up to five of
      the antibiotics tested. Metal resistance against Ni++, Zn++ and Cu++ was also
      detected. In accordance with these results, plasmids of low and high molecular
      weight were detected in 47 % of the isolates. Twenty-two partial 16S rDNA
      sequences analyzed allowed grouping the isolates within five different
      phyla/classes: Alpha-, Beta- and Gamma-proteobacteria, Actinobacteria and
      Flavobacteria. This is the first report concerning South American Andean glacial
      ice microorganisms.

PMID- 24085507
TI  - Adaptive properties of differential learning rates for positive and negative
      outcomes.
AB  - The concept of the reward prediction error-the difference between reward obtained
      and reward predicted-continues to be a focal point for much theoretical and
      experimental work in psychology, cognitive science, and neuroscience. Models that
      rely on reward prediction errors typically assume a single learning rate for
      positive and negative prediction errors. However, behavioral data indicate that
      better-than-expected and worse-than-expected outcomes often do not have symmetric
      impacts on learning and decision-making. Furthermore, distinct circuits within
      cortico-striatal loops appear to support learning from positive and negative
      prediction errors, respectively. Such differential learning rates would be
      expected to lead to biased reward predictions and therefore suboptimal choice
      performance. Contrary to this intuition, we show that on static "bandit" choice
      tasks, differential learning rates can be adaptive. This occurs because
      asymmetric learning enables a better separation of learned reward probabilities.
      We show analytically how the optimal learning rate asymmetry depends on the
      reward distribution and implement a biologically plausible algorithm that adapts
      the balance of positive and negative learning rates from experience. These
      results suggest specific adaptive advantages for separate, differential learning
      rates in simple reinforcement learning settings and provide a novel, normative
      perspective on the interpretation of associated neural data.

PMID- 24085506
TI  - Improvement in insulin sensitivity after human islet transplantation for type 1
      diabetes.
AB  - CONTEXT: Islet transplantation can improve metabolic control for type 1 diabetes
      (T1D), an effect anticipated to improve insulin sensitivity. However, current
      immunosuppression regimens containing tacrolimus and sirolimus have been shown to
      induce insulin resistance in rodents. OBJECTIVE: The objective of the study was
      to evaluate the effect of islet transplantation on insulin sensitivity in T1D
      using euglycemic clamps with the isotopic dilution method to distinguish between
      effects at the liver and skeletal muscle. DESIGN, SETTING, AND PARTICIPANTS:
      Twelve T1D subjects underwent evaluation in the Clinical and Translational
      Research Center before and between 6 and 7 months after the transplant and were
      compared with normal control subjects. INTERVENTION: The intervention included
      intrahepatic islet transplantation according to a Clinical Islet Transplantation
      Consortium protocol under low-dose tacrolimus and sirolimus immunosuppression.
      MAIN OUTCOME MEASURES: Total body (M/Deltainsulin), hepatic (1/endogenous glucose
      production .basal insulin) and peripheral [(Rd - endogenous glucose
      production)/Deltainsulin] insulin sensitivity assessed by hyperinsulinemic (1
      mU.kg(-1).min(-1)) euglycemic (~90 mg/dL) clamps with 6,6-(2)H2-glucose tracer
      infusion were measured. RESULTS: Glycosylated hemoglobin was reduced in the
      transplant recipients from 7.0% +/- 0.3% to 5.6% +/- 0.1% (P < .01). There were
      increases in total (0.11 +/- 0.01 to 0.15 +/- 0.02 dL/min.kg per microunit per
      milliliter), hepatic [2.3 +/- 0.1 to 3.7 +/- 0.4 * 10(2) ([milligrams per
      kilogram per minute](-1).(microunits per milliliter)(-1))], and peripheral (0.08
      +/- 0.01 to 0.12 +/- 0.02 dL/min.kg per microunit per milliliter) insulin
      sensitivity from before to after transplantation (P < .05 for all). All insulin
      sensitivity measures were less than normal in T1D before (P <= .05) and not
      different from normal after transplantation. CONCLUSIONS: Islet transplantation
      results in improved insulin sensitivity mediated by effects at both the liver and
      skeletal muscle. Modern dosing of glucocorticoid-free immunosuppression with low
      dose tacrolimus and sirolimus does not induce insulin resistance in this
      population.

PMID- 24085508
TI  - Is a single-site laparoendoscopic approach a real surgical advancement for the
      management of small renal masses?
AB  - Nephron-sparing surgery (NSS) ensures equivalent oncological results while
      improving overall survival compared with radical nephrectomy when applied to the
      treatment of small renal masses, moreover warm ischemia is associated with a risk
      of acute renal failure and advanced chronic kidney disease (CKD).
      Laparoendoscopic single-site (LESS) unclamp NSS is the next step forward in the
      management of small renal masses. From 2009 to 2013 we have treated 23 patients
      with small renal masses ( < 4 cm) amenable to the LESS approach using unclamp
      LESS NSS. In 20 cases we were able to complete the operation using LESS, in 3
      cases conversion to standard laparoscopy was required. Pathologic examination
      revealed 16 cases of clear-cell renal cell carcinoma (RCC), 4 cases of renal
      cysts, 2 oncocytomas, and 1 angiomyolipoma. We did not find any significant
      variation in renal function or any case of tumor recurrence, and the majority of
      the patients were very satisfied of the cosmetic results. LESS unclamp partial
      nephrectomy is a safe and feasible procedure, oncological outcomes are similar to
      standard laparoscopy, there is an advantage with respect to renal function and
      cosmesis, although the procedure is more technically demanding compared with
      standard laparoscopy.

PMID- 24085509
TI  - Preoperative blood management strategies for total hip arthroplasty.
AB  - Total hip arthroplasty is associated with marked blood loss, with the potential
      for up to 90% of patients requiring allogeneic transfusions. Also, perioperative
      induced anemia is associated with lower postoperative functional scores,
      increased mortality, increased cardiovascular risks, longer hospital stays, and
      postoperative infections. The purpose of this review was to analyze the recent
      evidence on preoperative blood management strategies utilized for total hip
      arthroplasty. Specifically, we evaluated the use of preoperative iron therapy,
      intravenous erythropoietin, and autologous blood donation. No single strategy was
      shown to be superior over another in reducing the need for allogeneic
      transfusions; however, a combination of these blood management strategies may
      result in improved blood loss outcomes. Larger prospective randomized studies
      comparing the individual strategies, as well as combination therapies, are needed
      to develop a concise statement on the most effective and efficient preoperative
      blood management treatment algorithms for total hip arthroplasty. 

PMID- 24085510
TI  - Safety of intraoperative electrophysiological monitoring (TES and EMG) for spinal
      and cranial lesions.
AB  - Intraoperative motor evoked potentials (MEP) and electromyography (EMG)
      monitoring in patients with spinal and cranial lesions is a valuable tool for
      prevention of postoperative motor deficits. The purpose of this study was to
      determine whether electrophysiological monitoring during skull base, spinal cord,
      and spinal surgery might be useful for predicting postoperative motor
      deterioration. From January 2012 to March 2013, thirty-three consecutive patients
      were studied using intraoperative monitoring (Nuvasive NV-M5 System) to check the
      integrity of brainstem, spinal cord, and nerve roots, recording transcranial
      motor evoked potentials (TcMEPs) and electromyography. Changes in MEPs and EMGs
      were related to postoperative deficits. Preoperative diagnosis included skull
      base and brainstem lesions (6 patients), spinal tumors (11 patients), spinal
      deformity (16 cases). Using TcMEPs and EMG is a practicable and safe method. MEPs
      are useful in any surgery in which the brainstem and spinal cord are at risk. EMG
      stimulation helps to identify an optimal trans-psoas entry point for an extreme
      lateral lumbar interbody fusion (XLIF) approach to protect against potential
      nerve injury. This neural navigation technique via a surgeon-interpreted
      interface assists the surgical team in safely removing lesions and accessing the
      intervertebral disc space for minimally invasive spinal procedures. 

PMID- 24085511
TI  - The influence of emotion on lexical processing: insights from RT distributional
      analysis.
AB  - In two lexical decision experiments, the present study was designed to examine
      emotional valence effects on visual lexical decision (standard and go/no-go)
      performance, using traditional analyses of means and distributional analyses of
      response times. Consistent with an earlier study by Kousta, Vinson, and Vigliocco
      (Cognition 112:473-481, 2009), we found that emotional words (both negative and
      positive) were responded to faster than neutral words. Finer-grained
      distributional analyses further revealed that the facilitation afforded by
      valence was reflected by a combination of distributional shifting and an increase
      in the slow tail of the distribution. This suggests that emotional valence
      effects in lexical decision are unlikely to be entirely mediated by early,
      preconscious processes, which are associated with pure distributional shifting.
      Instead, our results suggest a dissociation between early preconscious processes
      and a later, more task-specific effect that is driven by feedback from
      semantically rich representations.

PMID- 24085512
TI  - The prediction of blood-tissue partitions, water-skin partitions and skin
      permeation for agrochemicals.
AB  - BACKGROUND: There is considerable interest in the blood-tissue distribution of
      agrochemicals, and a number of researchers have developed experimental methods
      for in vitro distribution. These methods involve the determination of saline
      blood and saline-tissue partitions; not only are they indirect, but they do not
      yield the required in vivo distribution. RESULTS: The authors set out equations
      for gas-tissue and blood-tissue distribution, for partition from water into skin
      and for permeation from water through human skin. Together with Abraham
      descriptors for the agrochemicals, these equations can be used to predict values
      for all of these processes. The present predictions compare favourably with
      experimental in vivo blood-tissue distribution where available. The predictions
      require no more than simple arithmetic. CONCLUSIONS: The present method
      represents a much easier and much more economic way of estimating blood-tissue
      partitions than the method that uses saline-blood and saline-tissue partitions.
      It has the added advantages of yielding the required in vivo partitions and being
      easily extended to the prediction of partition of agrochemicals from water into
      skin and permeation from water through skin.

PMID- 24085513
TI  - Scrotal antegradesclerotherapy demonstrates anatomical variations on venous
      drainage in paediatric, adolescent and young adult varicoceles.
AB  - AIM OF THE STUDY: Anatomical variations on venous drainage in varicoceles are
      under-reported. We report our experience in scrotal antegrade sclerotherapy (SAS)
      for adolescent varicoceles. METHODS: Since 2011, 15 consecutive boys with left
      varicoceles were recruited. Under general anaesthesia, a 5-mm transverse incision
      was made at scrotal neck, testicular vein was cannulated at pampiniform plexus
      with venogram performed. Foam sclerosant by mixing sodium tetradecyl sulphate
      (STS), Lipiodol((r)) and air was slowly injected under fluoroscopy.
      Postoperatively the patients were followed-up for varicocele grading, testicular
      size, and complications. MAIN RESULTS: Median age at operation was 14 (10-19)
      years. 80 % had grade three varicoceles, 33.3 % had smaller left testis before
      operation. Intra-operative venogram showed three different anatomical variations.
      Group I: eleven patients (73.3 %) had single distinct internal spermatic vein;
      Group II: two patients demonstrated duplication of internal spermatic vein
      draining into left renal vein; Group III: two patients had pampiniform plexus
      draining to iliac and/or paraspinal veins. SAS was performed in Group I and II
      patients. Sclerosant volume injected ranged from 1.5 to 4.5 ml. In Group III
      patients, surgical ligation of testicular veins was performed rather than SAS to
      avoid uncontrolled systemic sclerosant spillage. Mean length of stay was 1.13
      day. One patient with scrotal haematoma and one other with minor wound dehiscence
      were managed conservatively. Mean follow-up period was 10.9 (1-22) months.
      Thirteen patients (86.7 %) achieved varicocele grading <= 1. There was no
      postoperative testicular atrophy, hydrocele and epididymo-orchitis. CONCLUSION:
      Scrotal antegrade sclerotherapy using STS foam is a safe and effective treatment
      for adolescent varicoceles. Anatomical variations on venous drainage in
      varicoceles are common.

PMID- 24085514
TI  - PAH metabolites, GST and EROD in European eel (Anguilla anguilla) as possible
      indicators for eel habitat quality in German rivers.
AB  - The stock of the European eel (Anguilla anguilla L.) continues to decline and has
      reached a new minimum in 2011. Poor health status of the spawners due to organic
      contaminants is one of the possible causes for this dramatic situation.
      Polycyclic aromatic hydrocarbons (PAHs) are ubiquitous contaminants, which are
      rapidly metabolized in vertebrates. EROD (ethoxyresorufin-O-deethylase) and GST
      (glutathione-S-transferase) are two enzymes involved in PAH detoxification in
      fish. In this study, PAH metabolites as well as EROD and GST activity in a large,
      comprising dataset of more than 260 migratory and pre-migratory eels from five
      large German river basin districts were used to describe PAH exposure and its
      metabolism as possible indicators for the habitat quality for eels. Eel from the
      river Elbe appear to be moderately contaminated with PAH. Highest mean values of
      PAH metabolites were analysed in fish from the river Rhine. However, the results
      suggest that contaminants such as PAH are metabolized in the fish and may have
      contributed to EROD activity in eels caught from the Elbe estuary to 600 km
      upstream. Since the eel's onset of cessation of feeding is closely linked to
      maturation and migration, we propose bile pigments as new indicators contributing
      to identify the proportion of migratory eel, which is crucial information for eel
      management plans. We showed that PAH metabolites normalized to bile pigments as
      well as EROD could be used to describe the habitat quality and might be suitable
      parameters in search for suitable stocking habitats.

PMID- 24085515
TI  - Use of hairy roots extracts for 2,4-DCP removal and toxicity evaluation by
      Lactuca sativa test.
AB  - 2,4-Dichlorophenol (2,4-DCP) is widely distributed in wastewaters discharged from
      several industries, and it is considered as a priority pollutant due to its high
      toxicity. In this study, the use of different peroxidase extracts for 2,4-DCP
      removal from aqueous solutions was investigated. Tobacco hairy roots (HRs), wild
      type (WT), and double-transgenic (DT) for tomato basic peroxidases (TPX1 and
      TPX2) were used to obtain different peroxidase extracts: total peroxidases (TPx),
      soluble peroxidases (SPx), and peroxidases ionically bound to the cell wall
      (IBPx). All extracts derived from DT HRs exhibited higher peroxidase activity
      than those obtained from WT HRs. TPx and IBPx DT extracts showed the highest
      catalytic efficiency values. The optimal conditions for 2,4-DCP oxidation were pH
      6.5, H2O2 0.5 mM, and 200 U mL(-1) of enzyme, for all extracts analyzed. Although
      both TPx extracts were able to oxidize different 2,4-DCP concentrations, the
      removal efficiency was higher for TPx DT. Polyethylene glycol addition slightly
      improved 2,4-DCP removal efficiency, and it showed some protective effect on TPx
      WT after 2,4-DCP oxidation. In addition, using Lactuca sativa test, a reduction
      of the toxicity of post removal solutions was observed, for both TPx extracts.
      The results demonstrate that TPx extracts from both tobacco HRs appear to be
      promising candidate for future applications in removing 2,4-DCP from wastewaters.
      This is particularly true considering that these peroxidase sources are
      associated with low costs and are readily available. However, TPx DT has
      increased peroxidase activity, catalytic efficiency, and higher removal
      efficiency than TPx WT, probably due to the expression of TPX1 and TPX2
      isoenzymes.

PMID- 24085516
TI  - Distribution of PCDD/Fs and dioxin-like PCBs in sediment and plants from a
      contaminated salt marsh (Tejo estuary, Portugal).
AB  - Concentrations and profiles of 2,3,7,8-substituted polychlorinated dibenzo-p
      dioxins, polychlorinated dibenzofurans (PCDD/Fs) and dioxin-like polychlorinated
      biphenyls (dl-PCBs) were investigated in sediment and plants collected from a
      salt marsh in the Tejo estuary, Portugal. The highest PCDD/F and dl-PCB
      concentrations were detected in uncolonized sediments, averaging 325.25 +/- 57.55
      pg g(-1) dry weight (dw) and 8,146.33 +/- 2,142.14 pg g(-1) dw, respectively. The
      plants Sarcocornia perennis and Halimione portulacoides growing in PCDD/F and dl
      PCB contaminated sediments accumulated contaminants in roots, stems, and leaves.
      It was observed that PCDD/F and dl-PCB concentrations in roots were significantly
      lower in comparison with stems and leaves. In general, concentration of
      SigmaPCDD/Fs and Sigmadl-PCBs in H. portulacoides tissues were found to be
      twofold higher than those in S. perennis, indicating a difference in the
      accumulation capability of both species. Furthermore, congener profiles changed
      between sediments and plant tissues, reflecting a selective accumulation of low
      chlorinated PCDD/Fs and non-ortho dl-PCBs in plants.

PMID- 24085518
TI  - Shared Ageing Research Models (ShARM): a new facility to support ageing research.
AB  - In order to manage the rise in life expectancy and the concomitant increased
      occurrence of age-related diseases, research into ageing has become a strategic
      priority. Mouse models are commonly utilised as they share high homology with
      humans and show many similar signs and diseases of ageing. However, the time and
      cost needed to rear aged cohorts can limit research opportunities. Sharing of
      resources can provide an ethically and economically superior framework to
      overcome some of these issues but requires dedicated infrastructure. Shared
      Ageing Research Models (ShARM) ( www.ShARMUK.org ) is a new, not-for-profit
      organisation funded by Wellcome Trust, open to all investigators. It collects,
      stores and distributes flash frozen tissues from aged murine models through its
      biorepository and provides a database of live ageing mouse colonies available in
      the UK and abroad. It also has an online environment (MICEspace) for collation
      and analysis of data from communal models and discussion boards on subjects such
      as the welfare of ageing animals and common endpoints for intervention studies.
      Since launching in July 2012, thanks to the generosity of researchers in UK and
      Europe, ShARM has collected more than 2,500 tissues and has in excess of 2,000
      mice registered in live ageing colonies. By providing the appropriate support,
      ShARM has been able to bring together the knowledge and experience of
      investigators in the UK and Europe to maximise research outputs with little
      additional cost and minimising animal use in order to facilitate progress in
      ageing research. 

PMID- 24085517
TI  - A Novel Method for the Assessment of Cortisol Hormone in Different Body Fluids
      Using A New Photo Probe Thiazole Derivative.
AB  - A low cost and accurate method for the detection and analytical determination of
      the cortisol in pharmaceutical preparation, blood serum and urine was developed.
      The method was based upon the enhancement of fluorescence intensity of the band
      at 424 nm of the photo probe by different cortisol concentrations in acetonitrile
      at (pH 5.7, lambdaex = 320 nm). The influence of the different parameters, e.g.
      pH, solvent, cortisol concentration and foreign ions concentrations that control
      the enhancement process of fluorescence intensity of the band of photo probe was
      critically investigated. The remarkable enhancement of the fluorescence intensity
      at 424 nm in acetonitrile by various concentrations of cortisol was successfully
      used as a photo- probe for the assessment of cortisol concentration. The
      calibration plot was achieved over the concentration range 8.0 * 10(-6)-5.5 * 10(
      9) mol L(-1) cortisol with a correlation coefficient of 0.998 and a detection
      limit of 4.7 * 10(-9) mol L(-1). The developed method is simple and proceeds
      without practical artifacts compared to the other determination methods. 

PMID- 24085519
TI  - Circadian clocks of faster developing fruit fly populations also age faster.
AB  - Age-related changes in circadian rhythms have been studied in several model
      organisms including fruit flies Drosophila melanogaster. Although a general trend
      of period (tau) lengthening, reduction in rhythm strength and eventual
      arrhythmicity with increasing age has been reported, age-related changes in
      circadian rhythms have seldom been examined in the light of differences in the
      rate of ageing of the organism. We used four populations of fruit flies D.
      melanogaster which were selected to develop faster (as pre-adults) to ask if
      circadian clocks of these flies age faster than their controls. After 55
      generations, the selected populations (FD) started developing ~29-h (~12 %)
      faster than the controls (BD) while their circadian clocks exhibited tau ~0.5-h
      shorter than the controls. We assayed the activity/rest behaviour and adult
      lifespan of virgin males from the FD and BD populations under constant dark (DD)
      conditions. The results revealed that FD flies live significantly shorter, and
      markers of ageing of circadian rhythms set-in earlier in the FD flies compared to
      the BD controls, which suggests that circadian clocks of faster developing flies
      age faster than controls. These results can be taken to suggest that ageing of
      circadian clocks in fruit flies D. melanogaster is a function of its
      physiological rather than chronological age. 

PMID- 24085520
TI  - Impairment of regeneration in aging: appropriateness or stochastics?
AB  - There is a viewpoint that suppression of the proliferative capacity of cells and
      impairment of the regeneration of tissues and organs in aging are a consequence
      of specially arisen during evolution mechanisms that reduce the risk of malignant
      transformation and, thus, protect against cancer. We believe that the restriction
      of cell proliferation in an aging multicellular organism is not a consequence of
      implementing a special program of aging. Apparently, such a program does not
      exist at all and aging is only a "byproduct" of the program of development,
      implementation of which in higher organisms suggests the need for the emergence
      of cell populations with very low or even zero proliferative activity, which
      determines the limited capacity of relevant organs and tissues to regenerate. At
      the same time, it is the presence of highly differentiated cell populations,
      barely able or completely unable to reproduce (neurons, cardiomyocytes,
      hepatocytes), that ensures the normal functioning of the higher animals and
      humans. Apparently, the impairment of regulatory processes, realized at the
      neurohumoral level, still plays the main role in the mechanisms of aging of
      multicellular organisms, not just the accumulation of macromolecular defects in
      individual cells. It seems that the quality of the cells themselves does not
      worsen with age as much as reliability of the organism control over cells, organs
      and tissues, which leads to an increase in the probability of death. 

PMID- 24085521
TI  - Tissue resident stem cells: till death do us part.
AB  - Aging is accompanied by reduced regenerative capacity of all tissues and organs
      and dysfunction of adult stem cells. Notably, these age-related alterations
      contribute to distinct pathophysiological characteristics depending on the tissue
      of origin and function and thus require special attention in a type by type
      manner. In this paper, we review the current understanding of the mechanisms
      leading to tissue-specific adult stem cell dysfunction and reduced regenerative
      capacity with age. A comprehensive investigation of the hematopoietic, the
      neural, the mesenchymal, and the skeletal stem cells in age-related research
      highlights that distinct mechanisms are associated with the different types of
      tissue stem cells. The link between age-related stem cell dysfunction and human
      pathologies is discussed along with the challenges and the future perspectives in
      stem cell-based therapies in age-related diseases. 

PMID- 24085523
TI  - Psychrotolerant antifungal Streptomyces isolated from Tawang, India and the shift
      in chitinase gene family.
AB  - A total of 210 Streptomyces were isolated from the soil samples of Tawang, India
      where temperature varied from 5  degrees C during daytime to -2  degrees C during
      the night. Based on antifungal activity, a total of 33 strains, putatively
      Streptomyces spp., were selected. Optimal growth temperature for the 33 strains
      was 16  degrees C, with growth occurring down to 6  degrees C but not above 30 
      degrees C. Phylogenetic analysis based on 16S rDNA sequences revealed the
      taxonomic affiliation of the 33 strains as species of Streptomyces. To examine
      the relatedness of the chitinase genes from six strong antifungal Streptomyces
      strains, a phylogenetic tree was constructed using the catalytic domain
      nucleotide sequences and resulted in seven distinct monophyletic groups. A
      quantitative PCR study for chitinase expressing ability revealed that of the six
      antifungal strains tested, the strain Streptomyces roseochromogenus TSR12 was the
      most active producer of family 18 chitinase genes. Streptomyces strains with
      enhanced inhibitory potential usually encode a family 19 chitinase gene; however,
      our present study did not show expression of this family in the six strains
      tested. 

PMID- 24085522
TI  - Host and viral transcriptional regulators in Sulfolobus: an overview.
AB  - The genus Sulfolobus includes microorganisms belonging to the domain Archaea, sub
      kingdom Crenarchaeota, living in geographically distant acidic hot springs. Their
      adaptation to such particular habitats requires finely regulated mechanisms of
      gene expression, among which, those modulated by sequence-specific transcription
      factors (TFs) play a key role. In this review, we summarize the current knowledge
      on the repertoires of TFs found in Sulfolobus spp. and their viruses, focusing on
      the description of their DNA-binding domains and their structure-function
      relationship. 

PMID- 24085525
TI  - Effects of local corticosteroid injection on electrical properties of abeta
      fibers in carpal tunnel syndrome.
AB  - Very few data are available on the structural and functional effects of
      corticosteroids on peripheral nerve fibers. This paper is addressed to verify
      possible changes in the functional properties of myelinated Abeta fibers of the
      median nerve in carpal tunnel syndrome (CTS) after a local injection of
      triamcinolone acetate. Thirteen subjects affected by mild CTS and 13 controls
      were selected. Clinical, electrophysiological, and ultrasonographic (cross
      sectional area: CSA) data of the median nerve were quantified at 0 (pre
      injection), and 1 month after triamcinolone injection at wrist. We analyzed the
      input-output curves constructed by plotting the response amplitude as a function
      of stimulus intensity. After corticosteroid injection, all patients experienced
      symptom relief, the median nerve CSA decreased, and the plateau value of the
      input-output curve was significant higher than before the treatment. Pre
      injection, we observed a significant inverse correlation between median nerve CSA
      and plateau value of the input-output curve, which remained significant even
      after the corticosteroid injection. The Abeta fibers with higher electrical
      threshold undergo conduction recovery after local corticosteroid injection. In
      CTS, combined mechanisms might contribute to resolution of symptoms: anti
      edema/anti-inflammatory action and direct effect on the electrical properties of
      the nerve fibers.

PMID- 24085524
TI  - Lactation reduces stress-caused dopaminergic activity and enhances GABAergic
      activity in the rat medial prefrontal cortex.
AB  - We investigated the effect of restraint on the release of dopamine, GABA and
      glutamate in the medial prefrontal cortex (mPFC) of lactating compared with
      virgin Wistar female rats; besides the expression of D1, neuropeptide Y Y2, GABA
      receptors and corticotropin-releasing factor (CRF). Results from microdialysis
      experiments showed that basal dopamine and GABA, but not glutamate,
      concentrations were higher in lactating rats. In virgin animals, immobilization
      caused significant increase in dopamine, whereas GABA was unchanged and glutamate
      reduced. In lactating animals, restrain significantly decreased dopamine
      concentrations and, in contrast to virgin animals, GABA and glutamate
      concentrations increased. We found a higher expression of CRF, as well as the D1
      and neuropeptide Y Y2 receptors in the left mPFC of virgin stressed rats; also,
      only stressed lactating animals showed a significant increase in immunopositive
      cells to GABA in the left cingulate cortex; meanwhile, a significant decrease was
      measured in virgin rats after stress in the left prelimbic region. The increased
      inhibition of the mPFC dopamine cells during stress and the down-regulated
      expression of the neuropeptide Y Y2 receptor may explain the lower CRF and
      hyporesponse to stress measured in lactating animals. Interestingly,
      participation of mPFC in stress regulation seems to be lateralized. 

PMID- 24085527
TI  - Otto von Bismarck is not the origin of old age at 65.

PMID- 24085526
TI  - Preclinical studies on neurobehavioral and neuromuscular effects of cocaine
      hydrolase gene therapy in mice.
AB  - Cocaine hydrolase gene transfer of mutated human butyrylcholinesterase (BChE) is
      evolving as a promising therapy for cocaine addiction. BChE levels after gene
      transfer can be 1,500-fold above those in untreated mice, making this enzyme the
      second most abundant plasma protein. Because mutated BChE is approximately 70 %
      as efficient in hydrolyzing acetylcholine as wild-type enzyme, it is important to
      examine the impact on cholinergic function. Here, we focused on memory and
      cognition (Stone T-maze), basic neuromuscular function (treadmill endurance and
      grip strength), and coordination (Rotarod). BALB/c mice were given adeno
      associated virus vector or helper-dependent adenoviral vector encoding mouse or
      human BChE optimized for cocaine. Age-matched controls received saline or
      luciferase vector. Despite high doses (up to 10(13) particles per mouse) and high
      transgene expression (1,000-fold above baseline), no deleterious effects of
      vector treatment were seen in neurobehavioral functions. The vector-treated mice
      performed as saline-treated and luciferase controls in maze studies and strength
      tests, and their Rotarod and treadmill performance decreased less with age. Thus,
      neither the viral vectors nor the large excess of BChE caused observable toxic
      effects on the motor and cognitive systems investigated. This outcome justifies
      further steps toward an eventual clinical trial of vector-based gene transfer for
      cocaine abuse. 

PMID- 24085528
TI  - Laparoscopically assisted radical vaginal hysterectomy versus radical abdominal
      hysterectomy for the treatment of early cervical cancer.
AB  - BACKGROUND: Cervical cancer is the second most common cancer among women and is
      the most frequent cause of death from gynaecological cancers worldwide. Standard
      surgical management for selected early-stage cervical cancer is radical
      hysterectomy. Traditionally, radical hysterectomy has been carried out via the
      abdominal route and this remains the gold standard surgical management of early
      cervical cancer. In recent years, advances in minimal access surgery have made it
      possible to perform radical hysterectomy with the use of laparoscopy with the aim
      of reducing the surgical morbidity and promoting a faster recovery. OBJECTIVES:
      To compare the effectiveness and safety of laparoscopically assisted radical
      vaginal hysterectomy (LARVH) and radical abdominal hysterectomy (RAH) in women
      with early-stage (1 to 2A) cervical cancer. SEARCH METHODS: We searched the
      Cochrane Gynaecological Cancer Group Trials Register, and Cochrane Register of
      Controlled Trials (CENTRAL) Issue 7, 2013, MEDLINE, and EMBASE up to July 2013.
      We also searched registers of clinical trials, abstracts of scientific meetings,
      reference lists of included studies and contacted experts in the field. SELECTION
      CRITERIA: Randomised controlled trials (RCTs) that compared laparoscopically
      assisted radical hysterectomy and radical abdominal hysterectomy, in adult women
      diagnosed with early (stage 1 to 2A) cervical cancer. DATA COLLECTION AND
      ANALYSIS: Two review authors independently abstracted data and assessed risk of
      bias. MAIN RESULTS: We found one RCT, which included 13 women, that met our
      inclusion criteria and this trial reported data on LARVH versus RAH.Women who
      underwent LARVH for treatment of early-stage cervical cancer appeared to have
      less blood loss compared with those who underwent RAH. The trial reported a
      borderline significant difference between the two types of surgery (median blood
      loss 400 mL (interquartile range (IQR): 325 to 1050) and 1000 mL (IQR: 800 to
      1025) for LARVH and RAH, respectively, P value = 0.05). RAH was associated with
      significantly shorter operation time compared with LARVH (median: 180 minutes
      with LARVH versus 138 minutes with RAH, P value = 0.05).There was no
      statistically significant difference in the risk of perioperative complications
      in women who underwent LARVH and RAH. The trial reported two (29%) and four (57%)
      cases of intraoperative and postoperative complications, respectively, in the
      LARVH group and no (0%) reported cases of intraoperative complications and five
      (83%) cases of postoperative complications in the RAH group. There were no
      reported cases of severe perioperative complications.Bladder and bowel
      dysfunction of either a transient or chronic nature remain major morbidities
      after radical hysterectomy, and the one included study showed that there may be
      significantly less after LARVH. AUTHORS' CONCLUSIONS: The included trial lacked
      statistical power due to the small number of women in each group and the low
      number of observed events. Therefore, the absence of reliable evidence, regarding
      the effectiveness and safety of the two surgical techniques for the management of
      early-stage cervical cancer, precludes any definitive guidance or recommendations
      for clinical practice. The trial did not report data on long-term outcomes, but
      was at moderate risk of bias due to very low numbers of included women.

PMID- 24085529
TI  - Microscopic research on a multi-source traditional Chinese medicine, Astragali
      Radix.
AB  - Astragali Radix is a widely and commonly used Chinese herbal medicine, which is
      derived from roots of Astragalus membranaceus var. mongholicus and Astragalus
      membranaceus. To find a quick and reliable method of distinguishing these two
      species of Astragali Radix and of determining the age of a sample, microscopic
      characteristics of the two species were compared using light microscopy. The
      results showed that the microscopic characteristics, such as number of layers of
      phellem, continuing lignified xylem bundles within spring wood and lignified
      parenchyma cells in the central part of the xylem could be used for the
      differentiation of the root of A. membranaceus from the root of A. membranaceus
      var. mongholicus. Growth rings (annual rings) were found for the first time in
      the roots of both species, and could determine the age of a sample. For the first
      time, radial fibers in both species of Astragali Radix and pipette-shaped fibers
      in A. membranaceus var. mongholicus were found. The structure of "rotten heart"
      cork tissue (decayed central xylem) and tubular cork tissue was carefully
      studied, and the arranged order of tissues in both "rotten heart" and tubular
      cork tissues is phelloderm and phellem from outside to inside, which is contrary
      to that in the periderm. 

PMID- 24085530
TI  - [Imaging modalities in psoriatic arthritis].
AB  - This review presents an overview of the range of imaging modalities used in the
      diagnostic evaluation of patients with psoriatic arthritis (PsA). Conventional
      radiography is used to detect structural changes of the joints and tendon
      attachments. These changes occur late in the course of PsA hence conventional
      radiography contributes little to the early detection of PsA; however, the
      detection of periosteal proliferations on radiographs allows a relatively
      specific diagnosis of PsA. Skeletal scintigraphy and computed tomography are
      rarely used in PsA. Arthrosonography (ultrasound of the joints) is gaining
      increasing importance in the early identification of inflammatory soft tissue
      signs of PsA in the peripheral joints. Sonography enables early detection of
      synovitis and tenosynovitis as well as superficial erosions and also inflammatory
      processes of the tendon attachments. Magnetic resonance imaging (MRI) is
      indispensable for identifying possible involvement of the axial skeleton.
      Moreover, it allows good visualization of periostitis and arthritis. High
      resolution microcomputed tomography is an interesting novel diagnostic tool which
      allows highly sensitive evaluation of the bone structure and can detect very tiny
      bone lesions where typical signs of PsA are omega-shaped erosions and small
      corona-like spikes. Another interesting new diagnostic technique is fluorescence
      optical imaging (FOI) with the Xiralite system which is highly sensitive for
      detecting inflammatory processes of the hands. 

PMID- 24085531
TI  - [Joint sonography in rheumatology].
AB  - Sonographic examination of joints has become a decisive component in
      rheumatological diagnostics and is now indispensible in the clinical routine. The
      exceptional representation of acute inflammatory soft tissue processes, very
      early recognition of bony destruction and the ubiquitous availability of the
      method have been major contributors to this success. In recent years there have
      been new developments in technology and in examination methods. The substantial
      importance of sonography for early detection of arthritis, differential
      diagnostics, therapy monitoring and estimation of prognosis is underlined by the
      continuously increasing number of international publications. Several scoring
      systems have been developed for small and large joints and have been proven not
      only under study conditions but also in practice. Subclinical inflammatory
      processes which are held responsible for the so-called silent progression can be
      detected using sonography. 

PMID- 24085532
TI  - Characterization of a wheat-Psathyrostachys huashanica Keng 4Ns disomic addition
      line for enhanced tiller numbers and stripe rust resistance.
AB  - Exploiting and utilizing excellent gene(s) from wild species has become an
      essential strategy for wheat improvement. In the disomic addition line 24-6-3,
      the 4Ns chromosomes from Psathyrostachys huashanica Keng (2n = 2x = 14, NsNs)
      carried valuable tiller and strip rust resistance gene(s), which was selected
      from the progeny of common wheat cv. 7182 and P. huashanica via embryo culture.
      Cytology, genomic in situ hybridization (GISH), and EST-STS analyses were used to
      detect the 4Ns chromosome in wheat background and its homoeologous relationship.
      Cytological studies demonstrated that 24-6-3 contained 44 chromosomes and formed
      22 bivalents during meiotic metaphase I. GISH using P. huashanica genomic DNA as
      a probe indicated that a pair of Ns-chromosomes with strong hybridization signals
      had been introduced into 24-6-3. Ten EST-STS markers, i.e., BE404973, BE442811,
      BE446061, BE446076, BE497324, BE591356, BF473854, BG274986, BQ161513 and
      CD373484, which were located on the homoeologous group 4 chromosomes of wheat,
      amplified bands unique to P. huashanica in 24-6-3. This indicated the presence of
      an introgressed P. huashanica Ns chromosome pair belonging to homoeologous group
      4, which we designated the 4Ns disomic addition line. After it was inoculated
      using mixed races of stripe rust in the adult stages, 24-6-3 expressed high
      stripe rust resistance, which was possibly derived from its P. huashanica parent.
      Moreover, its increased number of tillers was probably controlled by gene(s)
      located in P. huashanica chromosome 4Ns. These high levels of disease resistance
      and excellent agronomic traits make the 24-6-3 line a promising germplasm for
      breeding in wheat. 

PMID- 24085534
TI  - Narratives of sick leave, return to work and job mobility for people with common
      mental disorders in Sweden.
AB  - PURPOSE: The aim of this study was to analyze how different types of sick leave
      narratives were related to return to work (RTW), job mobility or continued sick
      leave for people sick-listed with common mental disorders. Special attention was
      paid to how the respondents described their contacts with employers and
      rehabilitation professionals. METHODS: Eight persons sick-listed with common
      mental disorders were interviewed at two occasions (2005-2006 and 2008-2009)
      about their self-perceptions, their sick leave, and their contacts with their
      employers and rehabilitation professionals, first during their first months as
      sick-listed, and a follow-up after approximately 4 years. RESULTS: Two types of
      narratives were identified: restitutive (with focus on recovery and RTW), and
      contingent (focusing on managing the present). A common theme was that mental
      problems were not recognized and talked about in the same way as physical
      problems. This had consequences for peoples' acceptance of their diagnoses and
      for the RTW processes. In restitutive narratives, RTW was essential for returning
      to life as it was, where support from managers and colleagues facilitated a
      successful return. In contingent narratives, the experience of sick leave was
      part of a broader story of change where work relations were of less importance.
      CONCLUSIONS: A narrative understanding of rehabilitation involves sensitivity
      toward the stories people are caught up in, and what role professionals may play
      in them. Promotion of job mobility may be difficult to accept for persons with
      restitutive narratives, while persons caught up in contingent narratives may be
      more open-and benefit more-from such solutions.

PMID- 24085533
TI  - Single-cell analysis of embryoid body heterogeneity using microfluidic trapping
      array.
AB  - The differentiation of pluripotent stem cells as embryoid bodies (EBs) remains a
      common method for inducing differentiation toward many lineages. However,
      differentiation via EBs typically yields a significant amount of heterogeneity in
      the cell population, as most cells differentiate simultaneously toward different
      lineages, while others remain undifferentiated. Moreover, physical parameters,
      such as the size of EBs, can modulate the heterogeneity of differentiated
      phenotypes due to the establishment of nutrient and oxygen gradients. One of the
      challenges in examining the cellular composition of EBs is the lack of analytical
      methods that are capable of determining the phenotype of all of the individual
      cells that comprise a single EB. Therefore, the objective of this work was to
      examine the ability of a microfluidic cell trapping array to analyze the
      heterogeneity of cells comprising EBs during the course of early differentiation.
      The heterogeneity of single cell phenotype on the basis of protein expression of
      the pluripotent transcription factor OCT-4 was examined for populations of EBs
      and single EBs of different sizes at distinct stages of differentiation. Results
      from the cell trap device were compared with flow cytometry and whole mount
      immunostaining. Additionally, single cells from dissociated pooled EBs or
      individual EBs were examined separately to discern potential differences in the
      value or variance of expression between the different methods of analysis.
      Overall, the analytical method described represents a novel approach for
      evaluating how heterogeneity is manifested in EB cultures and may be used in the
      future to assess the kinetics and patterns of differentiation in addition to the
      loss of pluripotency. 

PMID- 24085535
TI  - Cost-utility analysis of a collaborative care intervention for major depressive
      disorder in an occupational healthcare setting.
AB  - PURPOSE: Major depression is associated with high levels of absence and reduced
      productivity. Therefore the costs to society are high. The aim of this study was
      to evaluate the cost-utility of collaborative care for major depressive disorder
      (MDD) compared to care as usual in an occupational healthcare setting. A societal
      perspective was taken. METHODS: In this randomised controlled trial, 126 sick
      listed workers with MDD were included (65 collaborative care, 61 care as usual).
      Baseline measurements and follow up measures (3, 6, 9 and 12 months) were
      assessed by questionnaire. We applied the Trimbos/iMTA questionnaire for costs
      associated with psychiatric illness, the SF-HQL and the EQ-5D respectively
      measuring the health care utilization, production losses and general health
      related quality of life. RESULTS: The average annual healthcare costs in the
      collaborative care group were ?3,874 (95 % CI ?2,778-? 5,718) compared to ?4,583
      (95 % CI ?3,108-?6,794) in the care as usual group. The average quality of life
      years (QALY's) gained were lower in the collaborative care group, 0.05 QALY. The
      majority of the ICERS (69 %) indicate that collaborative care is less costly but
      also less effective than care as usual. Including the productivity costs did not
      change this result. CONCLUSIONS: The cost-utility analysis showed that
      collaborative care generated reduced costs and a reduction in effects compared to
      care as usual and was therefore not a cost-effective intervention.

PMID- 24085536
TI  - Optimized CGenFF force-field parameters for acylphosphate and N
      phosphonosulfonimidoyl functional groups.
AB  - We report an optimized set of CGenFF parameters that can be used to model small
      molecules containing acylphosphate and N-phosphonosulfonimidoyl functional groups
      in combination with the CHARMM force field. Standard CGenFF procedures were
      followed to obtain bonded interaction parameters, which were validated by
      geometry optimizations, comparison to the results of calculations at the MP2/6
      31+G(d) level of theory, and molecular dynamics simulations. In addition, partial
      atomic charges were assigned so that the energy of hydrogen bonding of the model
      compounds with water was correctly reproduced. The availability of these
      parameters will facilitate computational studies of enzymes that generate
      acyladenylate intermediates during catalytic turnover. In addition, given that
      the N-phosphonosulfonimidoyl moiety is a stable transition state analog for the
      reaction of ammonia with an acyladenylate, the parameters developed in this study
      should find use in efforts to develop novel and potent inhibitors of various
      glutamine-dependent amidotransferases that have been validated as drug targets.
      Topology and parameter files for the model compounds used in this study, which
      can be combined with other CGenFF parameters in computational studies of more
      complicated acylphosphates and N-phosphonosulfonimidates are made available.

PMID- 24085537
TI  - Binding selectivity studies of PKBalpha using molecular dynamics simulation and
      free energy calculations.
AB  - Designing selective protein kinase B (PKB/Akt) inhibitor is an area of intense
      research to develop potential anticancer drugs. In the present study, the
      molecular basis governing PKB-selective inhibition has been investigated using
      molecular dynamics simulation. The binding free energies calculated by MM/PBSA
      gave a good correlation with the experimental biological activity and a good
      explanation of the activity difference of the studied inhibitors. The
      decomposition of free energies by MM/GBSA indicates that the ethyl group on
      pyrrolo[2,3-d]pyrimidine ring of inhibitor Lig1 (N-{[(3S)-3-amino-1-(5-ethyl-7H
      pyrrolo[2,3-d]pyrimidin-4-yl)pyrrolidin-3-yl]-methyl}-2,4-difluoro-benzamide) is
      an important contributor to its PKBalpha selectivity due to its hydrophobic
      interaction with the side chain of Thr291 in PKBalpha. The substituted groups on
      the pyrrolidine ring of Lig1 also show a strong tendency to mediate protein
      ligand interactions through the hydrogen bonds formed between the amino or amide
      groups of Lig1 and the carboxyl O atoms of Glu234, Glu278, and Asp292 of
      PKBalpha. It was reported that there are only three key amino acid differences
      between PKBalpha (Thr211, Ala230, Met281) and PKA (Val104, Val123, Leu173) within
      the clefts of ATP-binding sites. These differences propel a drastic
      conformational change in PKA, weakening its binding interactions with inhibitor.
      The impact was also confirmed by MD simulated interaction modes of inhibitor
      binding to PKBalpha mutants with the in silico mutations of the three key amino
      acids, respectively. We expect that the results obtained here could be useful for
      future rational design of specific ATP-competitive inhibitors of PKBalpha.

PMID- 24085538
TI  - DFT model cluster studies of O2 adsorption on hydrogenated titania sub
      nanoparticles.
AB  - In the present paper, we examine the general applicability of different TiO2
      model clusters to study of local chemical events on TiO2 sub-nanoparticles. Our
      previous DFT study of TiO2 activation through H adsorption and following
      deactivation by O2 adsorption using small amorphous Ti8O16 cluster were
      complemented by examination of rutile-type and spherical Ti15O30 nanoclusters.
      The obtained results were thoroughly compared with experimental data and results
      of related computational studies using other TiO2 models including periodic
      structures. It turned out that all considered model TiO2 model systems provide
      qualitatively similar results. It was shown that atomic hydrogen is adsorbed with
      negligible activation energy on surface O atoms, which is accompanied by the
      appearance of reduced Ti(3+) species and corresponding localized band gap 3d-Ti
      states. Oxygen molecule is adsorbed on Ti(3+) sites spontaneously forming
      molecular O2 (-) species by capturing an extra electron of Ti(3+) ion, which
      results in disappearance of Ti(3+) species and corresponding band gap states.
      Calculated g-tensor values of Ti(3+) and O2 (-) species agree well with the
      results of EPR studies and do not depend on the used TiO2 model cluster.
      Additionally, it was shown that the various cluster calculations provide results
      comparable with the calculations of periodic structures with respect to the
      modeling of chemical processes under study. As a whole, the present study
      approves the validity of molecular cluster approach to study of local chemical
      events on TiO2 sub-nanoparticles.

PMID- 24085539
TI  - Gas phase acidities of N-substituted amine-boranes.
AB  - Complexation energies and acidities of 19 primary, secondary and tertiary amine
      boranes were investigated using MP2/6-311+G(d,p) and B3LYP/6-311+G(d,p) methods.
      Gas phase acidities for free amines were also calculated. Acidity values for
      studied complexes range from 327.3 to 349.1 kcal mol(-1) and the most acidic are
      the ones with direct connection between deprotonation center and a pi-system.
      Results obtained by both computational methods are in good agreement with each
      other and with known experimental data. Addition of BH3 increases the acidity of
      amines by 30 to 50 kcal mol(-1). This enhancement effect was compared to the
      respective effect witnessed in phosphine-boranes and traced back to changes of
      charge delocalization on nitrogen. A question about the structural stability of
      several deprotonated amine-borane anions in the gas phase was also raised.

PMID- 24085540
TI  - Commentary on: Hemiballismus: a rare neurological manifestation of AIDS
      infection.

PMID- 24085541
TI  - Moyamoya syndrome related to neurofibromatosis of type 1: a case report.

PMID- 24085542
TI  - Proteomic analysis of meningiomas.
AB  - Meningiomas represent one-third of all primary brain tumors and cause 35,000 new
      cases each year. Because of this high incidence, we sought to determine if there
      are proteomic differences between meningiomas and neighboring tissues. Two
      dimensional gel electrophoresis and mass spectrometry were used to detect
      differentially expressed proteins in tumor samples, using arachnoid tissue as a
      control. Western blot analysis was used to validate the identified candidate
      proteins. We obtained quantitative data on 112 proteins, 17 of which were down
      regulated and 26 of which were up-regulated in meningiomas relative to normal
      arachnoid tissue. Our analysis showed that the expression of galectin-3,
      vimentin, and endoplasmin was decreased significantly in meningiomas. The
      expression of 40S ribosomal protein S12, glutathione S-transferase P, and hypoxia
      up-regulated protein 1 was increased significantly (P < 0.05). The six above
      mentioned differentially expressed proteins might be closely involved with the
      development of meningiomas. The results of this study provide basic insights into
      the proteome of meningiomas and provide a preliminary database for further
      research to enhance understanding of meningioma development.

PMID- 24085543
TI  - Esterase D and gamma 1 actin level might predict results of induction therapy in
      patients with acute myeloid leukemia without and with maturation.
AB  - Development of modern proteomic methods in recent years has opened also new
      perspectives in the identification of new biomarkers which ensure more effective
      diagnosis, treatment monitoring and prediction of therapeutic outcome. We
      evaluated usefulness of comparative proteomics (MALDI-TOF) in two subtypes of
      acute myeloid leukemia (AML), M1 and M2, according to FAB classification. The
      bone marrow or blood cell proteomes were examined in 33 newly diagnosed patients
      before "3 + 7" induction therapy, after treatment and when the disease relapsed.
      We found that bone marrow and peripheral mononuclear cells from healthy
      volunteers revealed a number of quantitative and qualitative differences between
      the two proteomes, reflecting differences in the maturational status of normal
      cells. Such differences were not detected in our AML M1/M2 patients.
      Additionally, we found 9 proteins, which are potential biomarkers differentiating
      between the AML patients and healthy volunteers. Using comparative proteomics, we
      found that annexin I, glutathione transferase omega, esterase D and gamma 1 actin
      had prognostic significance. Applying statistical methods, we detected two
      proteins which might allow to predict results of induction therapy in AML M1/M2.
      One of them was esterase D, the higher concentration of which was associated with
      higher complete remission rate, and the other was gamma 1 actin, the higher
      concentration of which was related to resistance. In the article, we also
      discussed the role of these two proteins in the biology of AML, and we suggested
      potential usefulness of modification in induction therapy reflecting the presence
      of proteins.

PMID- 24085544
TI  - Prognostic value of Th17 cells in acute leukemia.
AB  - Th17 cells and their effector cytokines have emerged as important mediators in
      inflammatory and autoimmune diseases and serve as an ambitious field in current
      immunology research. Recent studies suggest a potential impact of Th17 cells on
      solid tumors but relatively little is known about their contribution in
      hematological malignancies. The current study was designed to investigate the
      possible involvement and clinical significance of circulating Th17 cells in acute
      leukemia. Flow cytometry was used to analyze percentages of Th17 cells in
      peripheral blood mononuclear cells from 93 acute leukemia patients (ALL, n = 30;
      AML, n = 63) and 40 healthy volunteers. Serum levels of IL-17 and IL-21 were
      measured using enzyme-linked immunosorbent assay. Circulating Th17 cells were
      increased in patients with acute leukemia (2.88 +/- 0.65% and 2.90 +/- 0.57% in
      ALL and AML patients, respectively) and were significantly higher than in healthy
      controls (1.10 +/- 0.28%; P = 0.001). Furthermore, pretreatment Th17 cells were
      reduced significantly in patients who achieved complete remission after induction
      therapy (2.25 +/- 0.44 % and 1.63 +/- 0.27% in ALL and AML patients,
      respectively, P < 0.0001). Serum levels of IL-17 and IL-21 were significantly
      elevated in acute leukemia patients. Kaplan-Meier curves revealed a significantly
      longer overall survival in patients with high Th17 levels (P = 0.029 and P =
      0.027 for ALL and AML, respectively). In the multivariate analysis, Th17 cells
      retained statistical significance for overall survival in patients with ALL (OR
      0.331; P = 0.043) and AML (OR 0.489; P = 0.032). These results strongly suggest
      Th17 cells as a powerful new prognostic determinant which could serve as a
      potential therapeutic target to modulate anti-tumor response in acute leukemia
      patients.

PMID- 24085545
TI  - Array-CGH as an adjuvant tool in cytogenetic diagnosis of pediatric MDS and JMML.
AB  - Myelodysplastic syndromes (MDS) and juvenile myelomonocytic leukemia (JMML) are
      rare clonal hematopoietic diseases presented in the childhood. Both diseases
      exhibit abnormal karyotype and/or monosomy of chromosome 7 in a subgroup of
      patients. We screened for copy number variations (CNVs) by array-comparative
      genomic hybridization (aCHG) the DNA from bone marrow of six MDS and four JMML
      pediatric patients. Array-CGH analysis identified five cases (50%) with monosomy
      7, disclosing the chromosome 7 monosomy in two patients whose samples could not
      be evaluated by other methods. We identified CNVs in six patients, one of which
      displayed loss of LMO2, an oncogene that plays a central role in hematopoietic
      development. Our results suggest that array-CGH is a reliable and accurate
      technique to identify genomic alterations in MDS and JMML.

PMID- 24085546
TI  - Distribution of plasma fatty acids is associated with response to chemotherapy in
      non-Hodgkin's lymphoma patients.
AB  - Our recent data have linked plasma phospholipid fatty acid (FA) profile in
      patients with non-Hodgkin's lymphoma (NHL) with the clinical stage and
      aggressiveness of the disease. Thus, we proposed that plasma FA status in these
      patients may influence the effect of chemotherapy. The aim of this work was to
      assess FA status in NHL patients undergoing chemotherapy in relation to their
      response to therapy. We analyzed plasma FA profile in 47 newly diagnosed NHL
      patients before chemotherapy, after 3 cycles and after the end of the planned
      chemotherapy. Patients were treated according to the hospital protocol: 28
      patients with cyclophosphamide, doxorubicin, vincristine and prednisone, 7 with
      other anthracycline-containing regimens, 4 patients with cyclophosphamide,
      vincristine and prednisone and 8 with fludarabine-based regimens. Rituximab was
      added in 22 patients. Ten patients who did not receive all planned chemotherapy
      due to death or toxicity (non-completers) had significantly lower (p < 0.05)
      baseline proportion of palmitoleic, linoleic, eicosapentaenoic and
      docosahexaenoic acid, as well as n-3 and n-6 FA, than the patients who completed
      chemotherapy (completers). Furthermore, the completers were divided according to
      the response to chemotherapy to complete remission (CR), stable disease and
      progressive disease (PD). Proportion of palmitic acid after the end of
      chemotherapy was the highest in the PD group, while stearic acid showed the
      opposite trend. Palmitoleic acid and all n-3 FA (18:3, 20:5, 22:5 and 22:6) were
      the highest in the patients in remission and the lowest in PD (p < 0.001).
      Linoleic acid decreased and arachidonic acid increased from the CR to the PD
      group (p < 0.001). These results suggest that aberrations in plasma FA may
      influence response to chemotherapy in patients with NHL.

PMID- 24085548
TI  - Impaired health status and the effect of pain and fatigue on functioning in
      clinical trial patients with systemic lupus erythematosus.
AB  - OBJECTIVE: Our study evaluated the impaired health status of clinical trial
      patients with systemic lupus erythematosus (SLE) and explored the relationship
      between changes in fatigue and pain and their effect on overall health status.
      METHODS: Pooled treatment and placebo data from a phase Ib clinical trial of
      adults with moderate/severe SLE were analyzed. Measures included patient-reported
      Medical Outcome Study Short Form-36 Survey, Version 2 (SF-36v2), Fatigue Severity
      Scale, and numeric rating scales (NRS) for pain and global health assessment and
      clinician-reported global assessment of disease activity (MDGA). Disease burden
      was compared to the US general population. Health status of responders and
      nonresponders on pain or fatigue were compared. RESULTS: The sample included 161
      patients with SLE, predominantly female (96%) and white (72%), with average age
      of 43 +/- 11 years. Mean SF-36v2 component summary scores reflected overall
      problems with physical [physical component summary (PCS); 35.2 +/- 9.7] and
      mental health (mental component summary; 40.9 +/- 12.9). Patients with SLE had
      worse health status on all SF-36v2 subscales than the US general population and
      comparable age and sex norms (effect size -0.51 to -2.15). Pain and fatigue
      responders had greater improvements on SF-36v2 scores (bodily pain, physical
      functioning, social functioning, PCS), patient global health assessment NRS, and
      MDGA than nonresponders. There was moderate agreement in responder status, based
      on global assessments by patients and clinicians (68.1%), with some discrepancy
      between patients who were MDGA responders but patient assessment nonresponders
      (27.7%). CONCLUSION: Improvements in patient-reported pain or fatigue correlated
      with improvements in overall health. Patient assessments offer a unique
      perspective on treatment outcomes. Patient-reported outcomes add value in
      understanding clinical trial treatment benefits.

PMID- 24085547
TI  - Axonal protein synthesis and the regulation of primary afferent function.
AB  - Local protein synthesis has been demonstrated in the peripheral processes of
      sensory primary afferents and is thought to contribute to the maintenance of the
      neuron, to neuronal plasticity following injury and also to regeneration of the
      axon after damage to the nerve. The mammalian target of rapamycin (mTOR), a
      master regulator of protein synthesis, integrates a variety of cues that regulate
      cellular homeostasis and is thought to play a key role in coordinating the
      neuronal response to environmental challenges. Evidence suggests that activated
      mTOR is expressed by peripheral nerve fibers, principally by A-nociceptors that
      rapidly signal noxious stimulation to the central nervous system, but also by a
      subset of fibers that respond to cold and itch. Inhibition of mTOR complex 1
      (mTORC1) has shown that while the acute response to noxious stimulation is
      unaffected, more complex aspects of pain processing including the setting up and
      maintenance of chronic pain states can be disrupted suggesting a route for the
      generation of new drugs for the control of chronic pain. Given the role of mTORC1
      in cellular homeostasis, it seems that systemic changes in the physiological
      state of the body such as occur during illness are likely to modulate the
      sensitivity of peripheral sensory afferents through mTORC1 signaling pathways.

PMID- 24085549
TI  - The safety and efficacy of noncorticosteroid triple immunosuppressive therapy in
      the treatment of refractory chronic noninfectious uveitis in childhood.
AB  - OBJECTIVE: To assess the safety and efficacy of noncorticosteroid triple
      immunosuppressive therapy in the treatment of refractory chronic noninfectious
      childhood uveitis. METHODS: Subjects were retrospectively selected from a
      database. Patients were included if they were diagnosed with chronic,
      noninfectious uveitis at 16 years of age or under and treated with triple
      immunosuppressive therapy for at least 6 months (following failure of a
      combination of 2 immunosuppressants). Patient demographics, diagnoses, duration
      of uveitis, drug dosages, active joint inflammation, and ophthalmologic data were
      recorded. Efficacy outcomes for triple therapy were recorded at 6 months.
      RESULTS: Thirteen patients with bilateral uveitis were included. Using
      Standardized Uveitis Nomenclature (SUN) criteria, at 6 months only 11 eyes (42%)
      had a 2-step improvement in anterior chamber cell inflammation (n = 26). In
      addition, 2 patients required additional oral corticosteroid treatment. There
      were 4 significant infectious adverse events during a total of 21.9 patient-years
      (PY) on triple therapy (0.18 events per PY). CONCLUSION: In this group of
      children with refractory uveitis, addition of a third immunosuppressive agent did
      not confer substantial benefit in redressing ocular inflammation and was
      associated with significant infections in a minority of patients.

PMID- 24085550
TI  - Screening for latent tuberculosis infection in patients with chronic inflammatory
      arthritis: discrepancies between tuberculin skin test and interferon-gamma
      release assay results.
AB  - OBJECTIVE: Screening for latent tuberculosis infection (LTBI) is mandatory before
      initiating biologics in patients with chronic inflammatory arthritis (CIA).
      However, few studies have evaluated the discrepancies between the results of
      tuberculin skin test (TST) and interferon-gamma release assays (IGRA) in these
      patients. The purpose of our study was to investigate factors associated with TST
      and IGRA results in a large cohort of patients with CIA before the introduction
      of biologics. METHODS: A total of 563 consecutive patients with CIA (293
      rheumatoid arthritis, 270 spondyloarthritis) and eligible for biologics were
      prospectively enrolled. Demographic, clinical, and biological data were recorded.
      Risk factors for LTBI were assessed. All patients underwent a TST, a chest
      radiograph, and an IGRA test (T-SPOT.TB). RESULTS: Agreement between the 2 tests
      was low (kappa = 0.16). The bacillus Calmette-Guerin (BCG) status was
      significantly associated with discordance between the 2 tests (p = 0.004). The
      TST positivity rate was 34.8%. Factors associated with a negative TST were female
      sex (p = 0.02) and immunosuppressive treatment (p = 0.003). The only LTBI risk
      factor associated with TST positivity was an abnormal chest radiograph (p =
      0.02). T-SPOT.TB was positive in 21.7% of patients and indeterminate in 15.6%.
      Previous active TB and chest radiograph abnormalities were associated with IGRA
      positivity (p = 0.008 and p = 3.9 * 10(-5), respectively). The BCG vaccination
      was associated with negative IGRA (p = 3 * 10(-4)). Indeterminate IGRA results
      were associated with age, C-reactive protein, and immunosuppressive treatment (p
      = 0.005, 0.007, and 0.004, respectively). CONCLUSION: Our data support the
      combined use of T-SPOT.TB and TST in patients with CIA before biologics
      introduction. However, despite these good diagnostic values, indeterminate
      results may complicate the use of IGRA.

PMID- 24085551
TI  - Breathing exercises for adults with asthma.
AB  - BACKGROUND: Breathing exercises have been widely used worldwide as a
      complementary therapy to the pharmacological treatment of people with asthma.
      OBJECTIVES: To evaluate the evidence for the efficacy of breathing exercises in
      the management of patients with asthma. SEARCH METHODS: The search for trials led
      review authors to review the literature available in The Cochrane Library,
      MEDLINE, EMBASE, PsycINFO, CINAHL and AMED and to perform handsearching of
      respiratory journals and meeting abstracts. Trial registers and reference lists
      of included articles were also consulted.The literature search has been updated
      to January 2013. SELECTION CRITERIA: We included randomised controlled trials of
      breathing exercises in adults with asthma compared with a control group receiving
      asthma education or, alternatively, with no active control group. DATA COLLECTION
      AND ANALYSIS: Two review authors independently assessed trial quality and
      extracted data. RevMan software was used for data analysis based on the fixed
      effect model. Continuous outcomes were expressed as mean differences (MDs) with
      confidence intervals (CIs) of 95%. Heterogeneity was assessed by inspecting the
      forest plots. The Chi(2) test was applied, with a P value of 0.10 indicating
      statistical significance. The I(2) statistic was implemented, with a value
      greater than 50% representing a substantial level of heterogeneity. MAIN RESULTS:
      A total of 13 studies involving 906 participants are included in the review. The
      trials were different from one another in terms of type of breathing exercise
      performed, number of participants enrolled, number and duration of sessions
      completed, outcomes reported and statistical presentation of data. Asthma
      severity in participants from the included studies ranged from mild to moderate,
      and the samples consisted solely of outpatients. The following outcomes were
      measured: quality of life, asthma symptoms, number of acute exacerbations and
      lung function. Eleven studies compared breathing exercise with inactive control,
      and two with asthma education control groups. All eight studies that assessed
      quality of life reported an improvement in this outcome. An improvement in the
      number of acute exacerbations was observed by the only study that assessed this
      outcome. Six of seven included studies showed significant differences favouring
      breathing exercises for asthma symptoms. Effects on lung function were more
      variable, with no difference reported in five of the eleven studies that assessed
      this outcome, while the other six showed a significant difference for this
      outcome, which favoured breathing exercises. As a result of substantial
      heterogeneity among the studies, meta-analysis was possible only for asthma
      symptoms and changes in the Asthma Quality of Life Questionnaire (AQLQ). Each
      meta-analysis included only two studies and showed a significant difference
      favouring breathing exercises (MD -3.22, 95% CI -6.31 to -0.13 for asthma
      symptoms; MD 0.79, 95% CI 0.50 to 1.08 for change in AQLQ). Assessment of risk of
      bias was impaired by incomplete reporting of methodological aspects of most of
      the included trials. AUTHORS' CONCLUSIONS: Even though individual trials reported
      positive effects of breathing exercises, no reliable conclusions could be drawn
      concerning the use of breathing exercises for asthma in clinical practice. This
      was a result of methodological differences among the included studies and poor
      reporting of methodological aspects in most of the included studies. However,
      trends for improvement are encouraging, and further studies including full
      descriptions of treatment methods and outcome measurements are required.

PMID- 24085552
TI  - ATG9A overexpression is associated with disease recurrence and poor survival in
      patients with oral squamous cell carcinoma.
AB  - ATG9A is an integral membrane protein required for autophagosome formation and a
      membrane carrier in the autophagy pathways. The present study was designed to
      investigate the expression of ATG9A in oral squamous cell carcinoma (OSCC).
      Clinically annotated tumor specimens from 90 patients with OSCC were subjected to
      immunohistochemistry using an antibody against ATG9A and immunoreactivity was
      scored using an immunoreactivity score (IRS). Scores were compared with clinical
      and pathologic data to assess association with outcome. Overexpression of ATG9A
      was defined as an IRS of >=9 by receiver operating characteristics curve analysis
      and was identified in 25 (28 %) of 90 cases. ATG9A overexpression was associated
      with disease recurrence and overall survival (OS) in both univariate (p = 0.030
      and 0.025, respectively) and multivariate (p = 0.026 and 0.038, respectively) Cox
      analyses. Kaplan-Meier plots also showed that patients with ATG9A overexpression
      had shorter 3-year OS (p = 0.017) and time to recurrence (p = 0.021) than those
      with low ATG9A expression. These results suggest that the presence of ATG9A in
      the cytoplasm of tumor cells may be an independent biomarker for disease
      recurrence and survival in patients with OSCC.

PMID- 24085553
TI  - Ultra-deep sequencing confirms immunohistochemistry as a highly sensitive and
      specific method for detecting BRAF V600E mutations in colorectal carcinoma.
AB  - The activating BRAF (V600) mutation is a well-established negative prognostic
      biomarker in metastatic colorectal carcinoma (CRC). A recently developed
      monoclonal mouse antibody (clone VE1) has been shown to detect reliably BRAF
      (V600E) mutated protein by immunohistochemistry (IHC). In this study, we aimed to
      compare the detection of BRAF (V600E) mutations by IHC, Sanger sequencing (SaS),
      and ultra-deep sequencing (UDS) in CRC. VE1-IHC was established in a cohort of 68
      KRAS wild-type CRCs. The VE1-IHC was only positive in the three patients with a
      known BRAF (V600E) mutation as assessed by SaS and UDS. The test cohort consisted
      of 265 non-selected, consecutive CRC samples. Thirty-nine out of 265 cases
      (14.7%) were positive by VE1-IHC. SaS of 20 randomly selected IHC negative tumors
      showed BRAF wild-type (20/20). Twenty-four IHC-positive cases were confirmed by
      SaS (24/39; 61.5%) and 15 IHC-positive cases (15/39; 38.5%) showed a BRAF wild
      type by SaS. UDS detected a BRAF (V600E) mutation in 13 of these 15 discordant
      cases. In one tumor, the mutation frequency was below our threshold for UDS
      positivity, while in another case, UDS could not be performed due to low DNA
      amount. Statistical analysis showed sensitivities of 100% and 63% and
      specificities of 95 and 100% for VE1-IHC and SaS, respectively, compared to
      combined results of SaS and UDS. Our data suggests that there is high concordance
      between UDS and IHC using the anti-BRAF(V600E) (VE1) antibody. Thus, VE1
      immunohistochemistry is a highly sensitive and specific method in detecting BRAF
      (V600E) mutations in colorectal carcinoma.

PMID- 24085554
TI  - Witnessing a violent death and smoking, alcohol consumption, and marijuana use
      among adolescents.
AB  - Witnessing violence has been linked to maladaptive coping behaviors such as
      smoking, alcohol consumption, and marijuana use. However, more research is
      required to identify mechanisms in which witnessing violence leads to these
      behaviors. The objectives of this investigation were to examine the association
      between witnessing a violent death and smoking, alcohol consumption, and
      marijuana use among adolescents, to identify whether exhibiting depressive
      symptoms was a mediator within this relationship, and to determine if those who
      had adult support in school were less likely to engage in risky health behaviors.
      Data were collected from a sample of 1,878 urban students, from 18 public high
      schools participating in the 2008 Boston Youth Survey. In 2012, we used
      multilevel log-binomial regression models and propensity score matching to
      estimate the association between witnessing a violent death and smoking, alcohol
      consumption, and marijuana use. Analyses indicated that girls who witnessed a
      violent death were more likely to use marijuana (relative risk (RR) = 1.09, 95%
      confidence interval (CI) = 1.02, 1.17), and tended towards a higher likelihood to
      smoke (RR = 1.06, 95% CI = 1.00, 1.13) and consume alcohol (RR = 1.07, 95% CI =
      0.97, 1.18). Among boys, those who witnessed a violent death were significantly
      more likely to smoke (RR = 1.20, 95% CI = 1.11, 1.29), consume alcohol (RR =
      1.30, 95% CI = 1.17, 1.45) and use marijuana (RR = 1.33, 95% CI = 1.21, 1.46).
      When exhibiting depressive symptoms was included, estimates were not attenuated.
      However, among girls who witnessed a violent death, having an adult at school for
      support was protective against alcohol consumption. When we used propensity score
      matching, findings were consistent with the main analyses among boys only. This
      study adds insight into how witnessing violence can lead to adoption of adverse
      health behaviors.

PMID- 24085556
TI  - Early loosening of a press-fit cup with ceramic-on-ceramic articulation: our
      early results.
AB  - INTRODUCTION: In this study, we present the short-term results of the Selexys TH+
      cup with the Ceramys inlay which is a press-fit cup with a ceramic-on-ceramic
      articulation. (Mathys, Bettlach, Switzerland). We compared the results with a
      retrospective-matched control group with a Delta PF cup (Lima, Udine, Italy),
      which is also a press-fit cup with a ceramic-on-ceramic articulation. MATERIALS
      AND METHODS: 257 elective hip arthroplasties with the Selexys TH+ cup in 250
      patients placed in 2009 and 2010 were analyzed and compared with a control group
      retrospective analysis of the uncemented Delta PF cup (Lima, Udine, Italy) placed
      in 2007 and 2008 in 208 patients (222 hips). Surgical technique and surgeons were
      identical in both groups. RESULTS: During a follow-up period of 3-21 months, 19
      aseptic loosenings (7.4 %) were found for the Selexys TH+ cup. The survival
      plotted by a Kaplan-Meier curve shows a 1-year survival of 87.4 %. The Lima Delta
      PF cup showed a 1-year survival of 99.5 %. Failure analysis showed no clear
      explanation for this early loosening. CONCLUSION: The Selexys TH+ cup combined
      with the Ceramys ceramic-on-ceramic inlay coupling show an unacceptable high
      early revision rate. Therefore, we advice against using this combination.

PMID- 24085557
TI  - Feasibility study on the potential of a spiral blade in osteoporotic distal femur
      fracture fixation.
AB  - INTRODUCTION: Osteoporotic fractures of the distal femur (primary as well as
      periprosthetic) are a growing problem in today's trauma and orthopaedic surgery.
      Therefore, this feasibility study should identify the biomechanical potential of
      a (commercially available) spiral blade in the distal femur as compared to a
      single screw without any additional plate fixation. Additionally, the influence
      of cement augmentation was investigated. MATERIALS AND METHODS: An artificial low
      density bone model was either instrumented with a perforated spiral blade or a 5
      mm locking screw only. Additionally, the influence of 1 ml cement augmentation
      was investigated. All specimens were tested with static pull-out and cyclic
      loading (50 to 250 N with an increment of 0.1 N/cycle). RESULTS: In the non
      augmented groups, the mean pull-out force was significantly higher for the blade
      fixation (p < 0.001). In the augmented groups, the difference was statistically
      not significant (p = 0.217). Augmentation could increase pull-out force
      significantly by 72 % for the blade and 156 % for the screw, respectively (p =
      0.001). The mean number of cycles to failure in the non-augmented groups was
      12,433 (SD 465) for the blade and 2,949 (SD 215) for the screw, respectively (p <
      0.001). In the augmented group, the blade reached 13,967 (SD 1,407) cycles until
      failure and the screw reached 4,413 (SD 1,598), respectively (p < 0.001).
      CONCLUSION: The investigated spiral blade was mechanically superior,
      significantly, as compared to a screw in the distal femur. These results back up
      the further development of a distal femoral blade with spiral blade fixation for
      the treatment of osteoporotic distal femur fractures.

PMID- 24085555
TI  - Therapeutic hepatocyte transplant for inherited metabolic disorders: functional
      considerations, recent outcomes and future prospects.
AB  - The applications, outcomes and future strategies of hepatocyte transplantation
      (HTx) as a corrective intervention for inherited metabolic disease (IMD) are
      described. An overview of HTx in IMDs, as well as preclinical evaluations in
      rodent and other mammalian models, is summarized. Current treatments for IMDs are
      highlighted, along with short- and long-term outcomes and the potential for HTx
      to supplement or supplant these treatments. Finally, the advantages and
      disadvantages of HTx are presented, highlighted by long-term challenges with
      interorgan engraftment and expansion of transplanted cells, in addition to the
      future prospects of stem cell transplants. At present, the utility of HTx is
      represented by the potential to bridge patients with life-threatening liver
      disease to organ transplantation, especially as an adjuvant intervention where
      severe organ shortages continue to pose challenges. 

PMID- 24085559
TI  - Device modeling of dye-sensitized solar cells.
AB  - We review the concepts and methods of modeling of the dye-sensitized solar cell,
      starting from fundamental electron transfer theory, and using phenomenological
      transport-conservation equations. The models revised here are aimed at describing
      the components of the current-voltage curve of the solar cell, based on small
      perturbation experimental methods, and to such an end, a range of phenomena
      occurring in the nanoparticulate electron transport materials, and at interfaces,
      are covered. Disorder plays a major role in the definition of kinetic parameters,
      and we introduce single particle as well as collective function definitions of
      diffusion coefficient and electron lifetime. Based on these fundamental
      considerations, applied tools of analysis of impedance spectroscopy are
      described, and we outline in detail the theory of recombination via surface
      states that is successful to describe the measured recombination resistance and
      lifetime. 

PMID- 24085558
TI  - Sleep deprivation, low self-control, and delinquency: a test of the strength
      model of self-control.
AB  - Recent work provides evidence that sleep deprivation is positively related to
      delinquency. In this study, we draw on Baumeister and colleagues' strength model
      of self-control to propose an explanation for this association. Specifically, we
      argue that low self-control is the construct that bridges the relationship
      between sleep deprivation and delinquency. To test the proposed model, we examine
      survey data drawn from a longitudinal multi-city cohort study of adolescents who
      were followed from birth through age 15 (N = 825; 50% female; 82% non-Hispanic
      white, 59% two-parent nuclear family). The results from regression models using
      latent factors indicate: sleep deprivation is positively related to low self
      control; low self-control is positively related to delinquency; and the
      relationship between sleep deprivation and delinquency is indirect and operates
      through low self-control. Impressively, these relationships emerged when
      accounting for potential background sources of spuriousness, including
      neighborhood context, depressive symptoms, parenting practices, unstructured
      socializing with peers, and prior delinquency. Implications and directions for
      future research are discussed.

PMID- 24085560
TI  - Device modelling of organic bulk heterojunction solar cells.
AB  - We review the methods used to simulate the optoelectronic response of organic
      solar cells and focus on the application of one-dimensional drift-diffusion
      simulations. We discuss how the important physical processes are treated and
      review some of the experiments necessary to determine the input parameters for
      device simulations. To illustrate the usefulness of drift-diffusion simulations,
      we discuss several case studies, addressing the influence of charged defects on
      transport in bipolar and unipolar devices, the influence of defects on
      recombination, device performance and ideality factors. To illustrate frequency
      domain simulations, we show how to determine the validity range of Mott-Schottky
      plots for thin devices. Finally, we discuss an example where optical simulations
      are used to calculate the parasitic absorption in contact layers. 

PMID- 24085561
TI  - Control of asymmetry in the radical addition approach to chiral amine synthesis.
AB  - The state-of-the-science in asymmetric free radical additions to imino compounds
      is presented, beginning with an overview of methods involving stereocontrol by
      various chiral auxiliary approaches. Chiral N-acylhydrazones are discussed with
      respect to their use as radical acceptors for Mn-mediated intermolecular
      additions, from design to scope surveys to applications to biologically active
      targets. A variety of aldehydes and ketones serve as viable precursors for the
      chiral hydrazones, and a variety of alkyl iodides may be employed as radical
      precursors, as discussed in a critical review of the functional group
      compatibility of the reaction. Applications to amino acid and alkaloid synthesis
      are presented to illustrate the synthetic potential of these versatile
      stereocontrolled carbon-carbon bond construction reactions. Asymmetric catalysis
      is discussed, from seminal work on the stereocontrol of radical addition to imino
      compounds by non-covalent interactions with stoichiometric amounts of catalysts,
      to more recent examples demonstrating catalyst turnover. 

PMID- 24085562
TI  - The neuroprotective effect exerted by oligodendroglial progenitors on
      ischemically impaired hippocampal cells.
AB  - Oligodendrocyte progenitor cells (OPCs) are the focus of intense research for the
      purpose of cell replacement therapies in acquired or inherited neurodegenerative
      disorders, accompanied by ongoing hypo/demyelination. Recently, it has been
      postulated that these glia-committed cells exhibit certain properties of neural
      stem cells. Advances in stem cell biology have shown that their therapeutic
      effect could be attributed to their ability to secret numerous active compounds
      which modify the local microenvironment making it more susceptible to restorative
      processes. To verify this hypothesis, we set up an ex vivo co-culture system of
      OPCs isolated from neonatal rat brain with organotypic hippocampal slices (OHC)
      injured by oxygen-glucose deprivation (OGD). The presence of OPCs in such co
      cultures resulted in a significant neuroprotective effect manifesting itself as a
      decrease in cell death rate and as an extension of newly formed cells in
      ischemically impaired hippocampal slices. A microarray analysis of broad spectrum
      of trophic factors and cytokines expressed by OPCs was performed for the purpose
      of finding the factor(s) contributing to the observed effect. Three of them-BDNF,
      IL-10 and SCF-were selected for the subsequent functional assays. Our data
      revealed that BDNF released by OPCs is the potent factor that stimulates cell
      proliferation and survival in OHC subjected to OGD injury. At the same time, it
      was observed that IL-10 attenuates inflammatory processes by promoting the
      formation of the cells associated with the immunological response. Those
      neuroprotective qualities of oligodendroglia-biased progenitors significantly
      contribute to anticipating a successful cell replacement therapy. 

PMID- 24085564
TI  - [In Process Citation].

PMID- 24085565
TI  - Exclusive neuronal expression of SUCLA2 in the human brain.
AB  - SUCLA2 encodes the ATP-forming beta subunit (A-SUCL-beta) of succinyl-CoA ligase,
      an enzyme of the citric acid cycle. Mutations in SUCLA2 lead to a mitochondrial
      disorder manifesting as encephalomyopathy with dystonia, deafness and lesions in
      the basal ganglia. Despite the distinct brain pathology associated with SUCLA2
      mutations, the precise localization of SUCLA2 protein has never been
      investigated. Here, we show that immunoreactivity of A-SUCL-beta in surgical
      human cortical tissue samples was present exclusively in neurons, identified by
      their morphology and visualized by double labeling with a fluorescent Nissl dye.
      A-SUCL-beta immunoreactivity co-localized >99 % with that of the d subunit of the
      mitochondrial F0-F1 ATP synthase. Specificity of the anti-A-SUCL-beta antiserum
      was verified by the absence of labeling in fibroblasts from a patient with a
      complete deletion of SUCLA2. A-SUCL-beta immunoreactivity was absent in glial
      cells, identified by antibodies directed against the glial markers GFAP and S100.
      Furthermore, in situ hybridization histochemistry demonstrated that SUCLA2 mRNA
      was present in Nissl-labeled neurons but not glial cells labeled with S100.
      Immunoreactivity of the GTP-forming beta subunit (G-SUCL-beta) encoded by SUCLG2,
      or in situ hybridization histochemistry for SUCLG2 mRNA could not be demonstrated
      in either neurons or astrocytes. Western blotting of post mortem brain samples
      revealed minor G-SUCL-beta immunoreactivity that was, however, not upregulated in
      samples obtained from diabetic versus non-diabetic patients, as has been
      described for murine brain. Our work establishes that SUCLA2 is expressed
      exclusively in neurons in the human cerebral cortex.

PMID- 24085563
TI  - Neurodegeneration in Parkinson's disease: interactions of oxidative stress,
      tryptophan catabolites and depression with mitochondria and sirtuins.
AB  - The biological underpinnings to the etiology and course of neurodegeneration in
      Parkinson's disease are an area of extensive research that has yet to produce an
      early biological marker or disease-slowing or preventative treatment. Recent
      conceptualizations of Parkinson's disease have integrated immuno-inflammation and
      oxidative and nitrosative stress occurring in depression, somatization and
      peripheral inflammation into the course of Parkinson's disease. We review the
      data showing the importance of immuno-inflammatory processes and oxidative and
      nitrosative stress in such classically conceived 'comorbidities', suggesting that
      lifetime, prodromal and concurrent depression and somatization may be intricately
      involved in the etiology and course of Parkinson's disease, rather than
      psychiatric comorbidities. This produces a longer term developmental perspective
      of Parkinson's disease, which incorporates tryptophan catabolites (TRYCATs),
      lipid peroxidation, sirtuins, cyclic adenosine monophosphate, aryl hydrocarbon
      receptor, and circadian genes. This integrates wider bodies of data pertaining to
      neuronal loss in Parkinson's disease, emphasizing how these interact with
      susceptibility genes to drive changes in mitochondria, blood-brain barrier
      permeability and intercellular signalling. We review this data here in the
      context of neurodegeneration in Parkinson's disease and to the future directions
      indicated for slowing disease progression. 

PMID- 24085566
TI  - MMAD: microarray microdissection with analysis of differences is a computational
      tool for deconvoluting cell type-specific contributions from tissue samples.
AB  - BACKGROUND: One of the significant obstacles in the development of clinically
      relevant microarray-derived biomarkers and classifiers is tissue heterogeneity.
      Physical cell separation techniques, such as cell sorting and laser-capture
      microdissection, can enrich samples for cell types of interest, but are costly,
      labor intensive and can limit investigation of important interactions between
      different cell types. RESULTS: We developed a new computational approach, called
      microarray microdissection with analysis of differences (MMAD), which performs
      microdissection in silico. Notably, MMAD (i) allows for simultaneous estimation
      of cell fractions and gene expression profiles of contributing cell types, (ii)
      adjusts for microarray normalization bias, (iii) uses the corrected Akaike
      information criterion during model optimization to minimize overfitting and (iv)
      provides mechanisms for comparing gene expression and cell fractions between
      samples in different classes. Computational microdissection of simulated and
      experimental tissue mixture datasets showed tight correlations between predicted
      and measured gene expression of pure tissues as well as tight correlations
      between reported and estimated cell fraction for each of the individual cell
      types. In simulation studies, MMAD showed superior ability to detect
      differentially expressed genes in mixed tissue samples when compared with
      standard metrics, including both significance analysis of microarrays and cell
      type-specific significance analysis of microarrays. CONCLUSIONS: We have
      developed a new computational tool called MMAD, which is capable of performing
      robust tissue microdissection in silico, and which can improve the detection of
      differentially expressed genes. MMAD software as implemented in MATLAB is
      publically available for download at http://sourceforge.net/projects/mmad/.

PMID- 24085567
TI  - Functional module identification in protein interaction networks by interaction
      patterns.
AB  - MOTIVATION: Identifying functional modules in protein-protein interaction (PPI)
      networks may shed light on cellular functional organization and thereafter
      underlying cellular mechanisms. Many existing module identification algorithms
      aim to detect densely connected groups of proteins as potential modules. However,
      based on this simple topological criterion of 'higher than expected
      connectivity', those algorithms may miss biologically meaningful modules of
      functional significance, in which proteins have similar interaction patterns to
      other proteins in networks but may not be densely connected to each other. A few
      blockmodel module identification algorithms have been proposed to address the
      problem but the lack of global optimum guarantee and the prohibitive
      computational complexity have been the bottleneck of their applications in real
      world large-scale PPI networks. RESULTS: In this article, we propose a novel
      optimization formulation LCP(2) (low two-hop conductance sets) using the concept
      of Markov random walk on graphs, which enables simultaneous identification of
      both dense and sparse modules based on protein interaction patterns in given
      networks through searching for LCP(2) by random walk. A spectral approximate
      algorithm SLCP(2) is derived to identify non-overlapping functional modules.
      Based on a bottom-up greedy strategy, we further extend LCP(2) to a new algorithm
      (greedy algorithm for LCP(2)) GLCP(2) to identify overlapping functional modules.
      We compare SLCP(2) and GLCP(2) with a range of state-of-the-art algorithms on
      synthetic networks and real-world PPI networks. The performance evaluation based
      on several criteria with respect to protein complex prediction, high level Gene
      Ontology term prediction and especially sparse module detection, has demonstrated
      that our algorithms based on searching for LCP(2) outperform all other compared
      algorithms. AVAILABILITY AND IMPLEMENTATION: All data and code are available at
      http://www.cse.usf.edu/~xqian/fmi/slcp2hop/.

PMID- 24085568
TI  - Spatial regulation dominates gene function in the ganglia chain.
AB  - MOTIVATION: To understand the molecular mechanisms of neurons, it is imperative
      to identify genomic dissimilarities within the heterogeneity of the neural
      system. This is especially true for neuronal disorders in which spatial
      considerations are of critical nature. For this purpose, Hirudo medicinalis
      provides here an ideal system in which we are able to follow gene expression
      along the central nervous system, to affiliate location with gene behavior.
      RESULTS: In all, 221.1 million high-quality short reads were sequenced on the
      Illumina Hiseq2000 platform at the single ganglion level. Thereafter, a de novo
      assembly was performed using two state-of-the-art assemblers, Trinity and Trans
      ABySS, to reconstruct a comprehensive de novo transcriptome. Classification of
      Trinity and Trans-ABySS transcripts produced a non-redundant set of 76 845 and
      268 355 transcripts (>200 bp), respectively. Remarkably, using Trinity, 82% of
      the published medicinal leech messenger RNAs was identified. For the innexin
      family, all of the 21 recently reported genes were identified. Spatial regulation
      analysis across three ganglia throughout the entire central nervous system
      revealed distinct patterns of gene expression. These transcriptome data were
      combined with expression distribution to produce a spatio-transcripto map along
      the ganglia chain. This study provides a resource for gene discovery and gene
      regulation in future studies.

PMID- 24085569
TI  - Compound cis-regulatory elements with both boundary and enhancer sequences in the
      human genome.
AB  - MOTIVATION: It has been suggested that presumably distinct classes of genomic
      regulatory elements may actually share common sets of features and mechanisms.
      However, there has been no genome-wide assessment of the prevalence of this
      phenomenon. RESULTS: To evaluate this possibility, we performed a bioinformatic
      screen for the existence of compound regulatory elements in the human genome. We
      identified numerous such colocated boundary and enhancer elements from human
      CD4(+) T cells. We report evidence that such compound regulatory elements possess
      unique chromatin features and facilitate cell type-specific functions related to
      inflammation and immune response in CD4(+) T cells.

PMID- 24085570
TI  - Suspension laryngoscopy using a curved-frame trans-oral robotic system.
AB  - PURPOSE: Suspension laryngoscopy has been employed for laryngeal diseases such as
      treatment for a polyp, cystoma, or granuloma. After securing a straight path with
      a laryngoscope, the surgeon inserts rigid instruments and examines the target
      lesion by using a microscope. However, many patients suffer from secondary
      complications due to the use of a rigid laryngoscope. In addition, about 11-12 %
      of patients cannot be operated on using laryngoscope because of anatomical
      restrictions. A surgical method to treat patients using a curved-frame trans-oral
      robotics system was developed. METHODS: A new surgical procedure is investigated
      using a new surgical robot system that employs a curved frame as a guide to
      insert flexible instruments into the target lesion. For this, a master-slave
      robotic system was developed, and the performance of the proposed procedure was
      tested by using a phantom laryngeal model. RESULTS: A routine laryngeal
      polypectomy procedure was simulated and performed using flexible instruments
      guided by a master-slave surgical robot in suspension laryngoscopy. CONCLUSION: A
      surgical robotic system was able to perform routine procedures to remove a polyp
      in the vocal cord under clinically realistic conditions on an adult phantom.

PMID- 24085571
TI  - Study of small proline-rich proteins (SPRRs) in health and disease: a review of
      the literature.
AB  - Epithelial tissues are specialized to protect underlying tissues from
      environmental influences such as physical and chemical agents, infection by
      invasive microorganisms as well as water and heat loss. They are grouped into
      simple, transitional and stratified epithelia, which line the cavities and
      surfaces of structures throughout the body, and also form glands, separate
      compartments, regulate the exchange of molecules and act as sensory organs.
      Stratified epithelia such as the epidermis and the gingival and hard palate
      mucosa are in constant renewal, with cells proliferating in the lower layers,
      while the intermediate stratum and outermost layers undergo a tissue-specific
      process of differentiation to form a protective cornified barrier. This review
      focuses on a subclass of structural proteins, the small proline-rich proteins
      (SPRRs), which constitute cornified cell envelope precursors. Several studies
      have suggested that the SPRRs are related to increased epithelial proliferation
      and to malignant processes. Hence, we also review the literature for more
      extensive and in-depth profile of these proteins in cancer and other diseases.
      The understanding of SPRR functions has advanced in recent years, but many
      important questions about their role in pathophysiological processes remain
      unanswered, which stimulate new studies and approaches. 

PMID- 24085572
TI  - Treatment of refractory chronic urticaria: current and future therapeutic
      options.
AB  - Chronic urticaria is a distressing disease that affects up to 1 % of the general
      population at a time point in life and may severely worsen the quality of life.
      First-line treatment has been based on antihistamines, and presently relies on
      the use of non-sedating, second-generation antihistamines; following the
      recommendations of the recent international guidelines, in patients who do not
      respond to antihistamines at licensed doses, the daily dosage of these drugs can
      be increased up to fourfold. Nonetheless, a significant proportion of patients
      with chronic urticaria remain poorly controlled; in these cases, alternative
      therapeutic approaches have to be considered. This article critically reviews all
      of the third- and fourth-line treatment options suggested for patients whose
      disease is refractory to antihistamines, including systemic corticosteroids,
      leukotriene receptor antagonists, several different anti-inflammatory drugs
      (dapsone, sulfasalazine, hydroxychloroquine), various immunosuppressive drugs
      (calcineurin inhibitors, methotrexate, cyclophosphamide, azathioprine,
      mycophenolate mofetil), intravenous immunoglobulin, and newer treatment options,
      such as omalizumab and other biologic drugs. In addition, the article examines
      possible future treatment options based on recent findings about pathogenic
      mechanisms, and considers the treatment of antihistamine-unresponsive urticaria
      in special conditions such as children and pregnancy/lactation. The evidence
      supporting the use of several of the discussed drugs is presently limited and
      thus insufficient to recommend their routine use; as a consequence, such
      compounds should be considered only in specific cases and in adequate settings. 

PMID- 24085573
TI  - Improved characterization of visual evoked potentials in multiple sclerosis by
      topographic analysis.
AB  - In multiple sclerosis (MS), the combination of visual, somatosensory and motor
      evoked potentials (EP) has been shown to be highly correlated with the Expanded
      Disability Severity Scale (EDSS) and to predict the disease course. In the
      present study, we explored whether the significance of the visual EP (VEP) can be
      improved with multichannel recordings (204 electrodes) and topographic analysis
      (tVEP). VEPs were analyzed in 83 MS patients (median EDSS 2.0; 52 % with history
      of optic neuritis; hON) and 47 healthy controls (HC). TVEP components were
      automatically defined on the basis of spatial similarity between the scalp
      potential fields (topographic maps) of single subjects' VEPs and reference maps
      generated from HC. Non-ambiguous measures of latency, amplitude and configuration
      were derived from the maps reflecting the P100 component. TVEP was compared to
      conventional analysis (cVEP) with respect to reliability in HC, validity using
      descriptors of logistic regression models, and sensitivity derived from receiver
      operating characteristics curves. In tVEP, reliability tended to be higher for
      measurement of amplitude (p = 0.06). Regression models on diagnosis (MS vs. HC)
      and hON were more favorable using tVEP- versus cVEP-predictors. Sensitivity was
      increased in tVEP versus cVEP: 72 % versus 60 % for diagnosis, and 88 % versus 77
      % for hON. The advantage of tVEP was most pronounced in pathological VEPs, in
      which cVEPs were often ambiguous. TVEP is a reliable, valid, and sensitive method
      of objectively quantifying pathological VEP in particular. In combination with
      other EP modalities, tVEP may improve the monitoring of disease course in MS.

PMID- 24085575
TI  - High interstitial fluid pressure promotes tumor progression through inducing
      lymphatic metastasis-related protein expressions in oral squamous cell carcinoma.
AB  - OBJECTIVE: The present study was carried out to analyze the interstitial fluid
      pressure (IFP) values in patients with oral squamous cell carcinoma and identify
      the relationship between the IFP and tumor prognosis. METHODS: We investigated
      tumor lymphatic metastasis-related protein (VEGFC, VEGFD and VEGFR3) expressions
      change on SCC-4 and SCC-9 cells subjected to increased extracellular pressure in
      vitro and analyzed the relationship between these proteins and IFP, and prognosis
      of patients with oral squamous cell carcinoma. RESULTS: The results showed that
      the elevated extracellular pressure significantly resulted in a dramatic increase
      of VEGFC, VEGFD and VEGFR3 protein expressions in OSCC. More important, the
      activation of VEGFC, VEGFD and VEGFR3 proteins through IFP elevation contributed
      to poor prognosis for patients with OSCC. CONCLUSIONS: These results suggest an
      important potential clinical application of measuring IFP, which can be used as a
      generic marker of prognosis evaluation and response to therapy. Furthermore,
      VEGFC, VEGFD and VEGFR3 may be useful targets in developing novel and specific
      therapeutic tool for OSCC patients with high IFP.

PMID- 24085574
TI  - Breast cancer management in the elderly.
AB  - The increase in life expectancy in the western world means that we are faced with
      patients diagnosed with breast cancer in old age with increasing frequency. The
      management of these cases is a challenge for the oncologist, who must take into
      account the conditions associated with advanced age and the lack of trials in
      this population. In this review, we addressed the incorporation of geriatric
      assessment methods that may be useful in making decisions, the particular
      biological characteristics of breast cancer in elderly patients and their
      treatment in both localized and advanced disease. Finally, we collected
      recommendations based on scientific evidence regarding the monitoring and life
      style after finishing treatment. 

PMID- 24085576
TI  - Tumor histological subtyping determined by hormone receptors and HER2 status
      defines different pathological complete response and outcome to dose-dense
      neoadjuvant chemotherapy in breast cancer patients.
AB  - PURPOSE: To assess the impact in pathological complete response (pCR) and outcome
      of two dose-dense neoadjuvant chemotherapy (DDNC) regimens among different
      histological subtypes determined by hormonal receptor (HR) and HER2 status in
      breast cancer patients. METHODS: A total of 127 breast cancer patients were
      treated with DDNC in two prospective studies. A: adriamycin 40 mg/m(2) on day (d)
      1 plus paclitaxel 150 mg/m(2) and gemcitabine 2,000 mg/m(2) on d2 for six cycles
      (n = 54). B: epirubicin 90 mg/m(2), cyclophosphamide 600 mg/m(2) on d1 for three
      cycles, followed by paclitaxel 150 mg/m(2) and gemcitabine 2,500 mg/m(2) on d1 +/
      trastuzumab according to HER2 status (n = 73). Histological subtypes of breast
      cancer were 49 % HR+/HER2-, 17.5 % HR+/HER2+, 13.5 % HR-/HER2+ and 20 % HR-/HER2
      . RESULTS: pCR (absence of invasive cells in breast and lymph node) was achieved
      in 35 patients (28 %). The pCR rate was significantly different between
      histological subtypes: HR+/HER2- (9 %), HR+/HER2+ (23 %), HR-/HER2+ (50 %), HR
      /HER2- (56 %) (p < 0.001). The median follow-up was 81 months (r: 15-150 months).
      HR-/HER2- tumor subtype had a significantly worse DFS compared to HR+/HER2- (p =
      0.02), RH+/HER2+ (p = 0.04) and HR-/HER2+ tumor subtypes (p = 0.02). HR-/HER2-
      tumor subtype had a significantly shorter OS compared to HR+/HER2- (p = 0.007),
      RH+/HER2+ (p = 0.05), and HR-/HER2+ (p = 0.03) tumor subtypes. However, no
      significant difference was observed in DFS and OS among HR-/HER2- tumors that
      achieved a pCR. CONCLUSIONS: HR-/HER2- and HR-/HER2+ subtypes had a high pCR rate
      to DDNC. HR-/HER2- tumors had a worse outcome compared to other tumor subtypes
      but no significant difference was observed among HR-/HER2- tumors that achieved a
      pCR.

PMID- 24085578
TI  - THIS1 is a putative lipase that regulates tillering, plant height, and spikelet
      fertility in rice.
AB  - Proper branching and successful reproductive growth is of great importance for
      rice productivity. Substantial progress has been made in uncovering the molecular
      mechanisms underlying tillering control and spikelet sterility. However, rice
      tillering is developmentally controlled, and how it is regulated coordinately
      with reproductive growth remains unclear. This study characterized a rice mutant,
      the most obvious phenotypes of which are high tillering, reduced height, and
      infertile spikelets (named this1). Similarly to the high tiller number and dwarf
      mutants in rice, the increased tiller number of this1 plants is ascribed to the
      release of tiller bud outgrowth rather than to increased tiller bud formation. In
      the this1 mutant, however, the accelerated rate of branching was delayed until
      the stem elongation stage, while other mutants lost the ability to control
      branching at all developmental stages. The seed-setting rate of this1 was less
      than half that of the wild type, owing to defects in pollen maturation, anther
      dehiscence, and flower opening. Histological analyses showed that the mutation in
      this1 resulted in anisotropic cell expansion and cell division. Using a map-based
      cloning approach, This1 was found to encode a class III lipase. Homology searches
      revealed that THIS1 is conserved in both monocots and eudicots, suggesting that
      it plays fundamental role in regulating branch and spikelet fertility, as well as
      other aspects of developmental control. The relative change in expression of
      marker genes highlighted the possibility that This1 is involved in phytohormone
      signalling pathways, such as those for strigolactone and auxin. Thus, This1
      provides joint control between shoot branching and reproductive development. 

PMID- 24085577
TI  - Populus euphratica XTH overexpression enhances salinity tolerance by the
      development of leaf succulence in transgenic tobacco plants.
AB  - Populus euphratica is a salt-tolerant tree species that develops leaf succulence
      after a prolonged period of salinity stress. In the present study, a putative
      xyloglucan endotransglucosylase/hydrolase gene (PeXTH) from P. euphratica was
      isolated and transferred to tobacco plants. PeXTH localized exclusively to the
      endoplasmic reticulum and cell wall. Plants overexpressing PeXTH were more salt
      tolerant than wild-type tobacco with respect to root and leaf growth, and
      survival. The increased capacity for salt tolerance was due mainly to the
      anatomical and physiological alterations caused by PeXTH overexpression. Compared
      with the wild type, PeXTH-transgenic plants contained 36% higher water content
      per unit area and 39% higher ratio of fresh weight to dry weight, a hallmark of
      leaf succulence. However, the increased water storage in the leaves in PeXTH
      transgenic plants was not accompanied by greater leaf thickness but was due to
      highly packed palisade parenchyma cells and fewer intercellular air spaces
      between mesophyll cells. In addition to the salt dilution effect in response to
      NaCl, these anatomical changes increased leaf water-retaining capacity, which
      lowered the increase of salt concentration in the succulent tissues and mesophyll
      cells. Moreover, the increased number of mesophyll cells reduced the
      intercellular air space, which improved carbon economy and resulted in a 47-78%
      greater net photosynthesis under control and salt treatments (100-150 mM NaCl).
      Taken together, the results indicate that PeXTH overexpression enhanced salt
      tolerance by the development of succulent leaves in tobacco plants without
      swelling.

PMID- 24085579
TI  - Tobacco LSU-like protein couples sulphur-deficiency response with ethylene
      signalling pathway.
AB  - Most genes from the plant-specific family encoding Response to Low Sulphur (LSU)
      like proteins are strongly induced in sulphur (S)-deficient conditions. The exact
      role of these proteins remains unclear; however, some data suggest their
      importance for plants' adjustment to nutrient deficiency and other environmental
      stresses. This work established that the regulation of ethylene signalling is a
      part of plants' response to S deficiency and showed the interaction between UP9C,
      a tobacco LSU family member, and one of the tobacco isoforms of 1
      aminocyclopropane-1-carboxylic acid oxidase (ACO2A). Increase in ethylene level
      induced by S deficiency does not take place in tobacco plants with UP9C expressed
      in an antisense orientation. Based on transcriptomics data, this work also
      demonstrated that the majority of tobacco's response to S deficiency is
      misregulated in plants expressing UP9C-antisense. A link between response to S
      deficiency, ethylene sensing, and LSU-like proteins was emphasized by changes in
      expression of the genes encoding ethylene receptors and F-box proteins specific
      for the ethylene pathway. 

PMID- 24085580
TI  - A bacterial quercetin oxidoreductase QuoA-mediated perturbation in the
      phenylpropanoid metabolic network increases lignification with a concomitant
      decrease in phenolamides in Arabidopsis.
AB  - Metabolic perturbations by a gain-of-function approach provide a means to alter
      steady states of metabolites and query network properties, while keeping enzyme
      complexes intact. A combination of genetic and targeted metabolomics approach was
      used to understand the network properties of phenylpropanoid secondary metabolism
      pathways. A novel quercetin oxidoreductase, QuoA, from Pseudomonas putida, which
      converts quercetin to naringenin, thus effectively reversing the biosynthesis of
      quercetin through a de novo pathway, was expressed in Arabidopsis thaliana. QuoA
      transgenic lines selected for low, medium, and high expression levels of QuoA RNA
      had corresponding levels of QuoA activity and hypocotyl coloration resulting from
      increased anthocyanin accumulation. Stems of all three QuoA lines had increased
      tensile strength resulting from increased lignification. Sixteen metabolic
      intermediates from anthocyanin, lignin, and shikimate pathways had increased
      accumulation, of which 11 paralleled QuoA expression levels in the transgenic
      lines. The concomitant upregulation of the above pathways was explained by a
      significant downregulation of the phenolamide pathway and its precursor,
      spermidine. In a tt6 mutant line, lignifications as well as levels of the lignin
      pathway metabolites were much lower than those of QuoA transgenic lines. Unlike
      QuoA lines, phenolamides and spermidine were not affected in the tt6 line. Taken
      together, these results suggest that phenolamide pathway plays a major role in
      directing metabolic intermediates into the lignin pathway. Metabolic
      perturbations were accompanied by downregulation of five genes associated with
      branch-point enzymes and upregulation of their corresponding products. These
      results suggest that gene-metabolite pairs are likely to be co-ordinately
      regulated at critical branch points. Thus, these perturbations by a gain-of
      function approach have uncovered novel properties of the phenylpropanoid
      metabolic network. 

PMID- 24085581
TI  - The tomato NAC transcription factor SlNAM2 is involved in flower-boundary
      morphogenesis.
AB  - Being composed of several whorls of distinct floral organs, the flower is one of
      the most complex organs in the plant. As such, the formation and maintenance of
      boundaries that separate the meristem from the floral organ primordium and
      adjacent organs are critical for its normal development. In Arabidopsis, the
      miR164-regulated NAM genes play key roles in floral-boundary specification. By
      contrast, much less is known about floral-boundary establishment in the model
      crop tomato. It was found that the miR164-regulated NAM gene GOBLET is expressed
      in the floral meristem-organ boundaries and its loss-of-function mutant produces
      flowers with fused organs, indicating its requirement for tomato floral-boundary
      formation. It was found here that sly-miR164 targets the transcripts of three
      additional uncharacterized NAM genes in developing flowers. It is shown that,
      after floral-boundary initiation, the NAM gene Solyc03g115850 (SlNAM2) is
      expressed as stripes that mark the boundaries between sepals and between
      different floral whorls. Furthermore, ectopic accumulation of SlNAM2-encoding
      transcripts caused various growth-suppression and extraorgan phenotypes typically
      observed in plants over-expressing known boundary genes. Flower-specific
      silencing of sly-miR164-targeted NAM genes (AP1>>MIR164) caused defects in the
      separation of sepals and floral whorls indicating abnormal boundary
      specification. However, supplementing these NAM-deficient flowers with miR164
      resistant SlNAM2 suppressed their fusion phenotypes and completely restored
      floral boundaries. Together, our results strongly suggest that SlNAM2
      participates in the establishment of tomato flower whorl and sepal boundaries. 

PMID- 24085582
TI  - Autism in a recently arrived immigrant population.
AB  - This study aims to establish whether children of an immigrant maternal population
      presented with a higher rate of autism than the indigenous population and to
      explore their presentation with regard to severity of symptoms, demographics and
      ethnicity. It is a retrospective case note analysis of 366 children who presented
      to the paediatric developmental service in the Adelaide and Meath incorporating
      the National Children's Hospital, Tallaght, Ireland between 2007 and 2009. During
      the study period, 366 children presented. Fifty-eight children (16 %) had mothers
      who were born in Africa and 53 (14 %) were born to mothers originating from a
      wider variety of countries. Two hundred and forty-eight children (68 %) had
      mothers born in Ireland. Maternal origin was not identified for seven children (2
      %). An autistic spectrum disorder (ASD) was diagnosed in 131 children and speech
      and language delay in 132. Of the children with an ASD diagnosis, a higher
      proportion of the African cohort 13/18 (72.2 %) presented with moderate/severe
      cognitive disability compared to the Irish group 9/55(16.3 %), and the children
      in the African cohort showed a higher heritability with 36.9 % having a positive
      family history of autism reported compared to 26.3 % of the Irish cohort with an
      ASD diagnosis. CONCLUSION: This study highlights an observation of increased
      rates of ASD among a migrant population derived particularly from children born
      to mothers originating in Sub-Saharan Africa. This cohort is more severely
      affected. Further validation in an epidemiological sample is warranted, which if
      replicated, may help to identify possible aetiological risk factors.

PMID- 24085583
TI  - Cervical Pap screening among Israeli women, 2005-2010.
AB  - PURPOSE: This study describes the distribution and the trends of cervical
      abnormalities in Israel, based on Pap smear results. METHODS: A retrospective
      analysis of cervical smears received by the Central Pathology Laboratory of
      Maccabi Healthcare Services between January 2005 and December 2010. RESULTS: In
      total, 711,541 Pap smears were screened in the study period. Cytological
      abnormalities were observed in 4.78% of the total smears screened. An increase
      was observed in the rate of positive results from 2.63% in 2005 to 6.78% in 2010
      (p = 0.0026). The cervical abnormalities in the study period distributed as
      follows: atypical squamous cell (ASC)-2.72%, low-grade squamous intraepithelial
      lesion (LSIL)-1.54%, high-grade squamous intraepithelial lesion (HSIL)-0.34%,
      squamous cell carcinoma-0.01%, atypical glandular cells (AGC)-0.10%,
      adenocarcinoma in situ (AIS)-0.06% and invasive adenocarcinoma-0.01%. The
      increase was statistically significant for ASC (p = 0.0028), LSIL (p = 0.0069)
      and for HSIL (p = 0.0260). The mean ages at diagnosis of women with ASCUS, LSIL,
      HSIL, squamous cell carcinoma, AGC, AIS and adenocarcinoma were 37.8, 33.2, 38.6,
      55.4, 41.1, 49.9 and 57.1 years, respectively. CONCLUSIONS: The increase in the
      rate of squamous cell abnormalities demonstrated in this study emphasizes the
      need of implementing an education and a screening program among Israeli women.
      HPV vaccine, sexual behavior, cytology performance and HPV test are primary and
      secondary prevention tools which may reduce morbidity and mortality in the
      future. In addition, based on the age at diagnosis of the different pathologies,
      the age group in which Pap test is performed in Israel should be expanded from 35
      54 to 25-65 years.

PMID- 24085584
TI  - Cloning of sarco/endoplasmic reticulum Ca(2+)-ATPase (SERCA) gene from white
      shrimp, Litopenaeus vannamei and its expression level analysis under salinity
      stress.
AB  - Sarco/endoplasmic reticulum Ca(2+)-ATPase (SERCA) is an intracellular membrane
      bound enzyme that utilizes the free energy of ATP to transport Ca(2+) against a
      concentration gradient. In the present study, a new SERCA gene (LvSERCA) from
      white shrimp (Litopenaeus vannamei) was cloned using suppression subtractive
      hybridization and rapid amplification of cDNA ends. The full-length cDNA of
      LvSERCA contained an open reading frame of 3,009 bp coding for 1,002 amino acids
      with a calculated molecular weight of approximately 109.8 kDa. The identity
      analysis of the amino acid sequence of LvSERCA showed that it is highly conserved
      with 10 transmembrane alpha-helices, one P-domain, one A-domain and one N-domain.
      The phylogenetic analysis revealed that LvSERCA is similar to other Arthropoda
      SERCA proteins. The mRNA levels of LvSERCA under salinity stress (3 and 40 g L(
      1)) were analyzed by reverse transcription PCR and quantitative real-time PCR.
      The results showed that LvSERCA was expressed in all tissues detected. LvSERCA
      mRNA levels were significantly higher under hyper-salinity than hypo-salinity.
      These results highlight that Ga(2+)-ATPase plays an essential role in adjustment
      salinity stress, which may be useful for selective breeding of L. vannamei. 

PMID- 24085585
TI  - Circulating leptin levels and risk of colorectal cancer and adenoma: a case
      control study and meta-analysis.
AB  - PURPOSE: Equivocal results regarding the role of leptin in colorectal cancer
      (CRC) and adenoma (CRA) have been reported. A case-control study investigating
      the association of leptin with CRC risk and clinicopathological characteristics
      along with meta-analysis of published data on both CRC and CRA were conducted.
      METHODS: Pubmed and Embase were searched for the meta-analysis, comprising 28
      case-control studies amounting 3,614 CRC and 1,215 CRA cases, along with 5,220
      controls. Meticulous contact with the authors of individual studies was
      undertaken for the provision of additional data. Pooling of standardized mean
      differences (SMD), relative risks (RR) and 95 % CI (random effects models),
      subgroup, sensitivity, and meta-regression analyses were conducted. RESULTS: The
      meta-analysis suggested positive association of serum leptin with CRA (RR, 95 %
      CI 1.35, 1.03 to +1.76), but not CRC either at the pooled analysis on SMDs or RRs
      (SMD, 95 % CI 0.18, -0.04 to +0.40; RR, 95 % CI 1.04, 0.65 to +1.65). Significant
      heterogeneity between studies on CRC as well as between studies on CRA providing
      SMD was noted. Subgroup, meta-regression and sensitivity analyses highlighted
      potential methodology-, design-, size- and quality-related effect modifiers.
      CONCLUSIONS: Meta-analysis of current evidence suggests positive association of
      serum leptin with CRA but not with CRC risk. Given the case-control nature of
      available studies, the limited number of studies on serum leptin and CRA, and the
      heterogeneity of CRC studies, carefully designed, prospective studies preferably
      reporting RRs adjusted for a variety of confounders may be warranted.

PMID- 24085586
TI  - A prospective study of smoking and breast cancer risk among African-American
      women.
AB  - PURPOSE: Active smoking and passive smoking have been associated with increased
      risk of breast cancer. The purpose of the present study was to prospectively
      assess associations of smoking with breast cancer and identify subgroups at
      higher risk among African-American women. METHODS: Based on 1,377 incident cases
      identified during 14 years of follow-up in the Black Women's Health Study, we
      assessed active and passive smoking in relation to breast cancer incidence by
      menopausal status, estrogen receptor status, and other factors. Incidence rate
      ratios (IRR) and 95 % confidence intervals (CI) for categories of smoking
      relative to no active or passive smoking were calculated from Cox proportional
      hazards models, controlling for breast cancer risk factors. RESULTS: Active
      smoking was associated with increased risk of premenopausal breast cancer. The
      IRR was 1.21 (95 % CI 0.90-1.62) for premenopausal breast cancer overall and 1.70
      (95 % CI 1.05-2.75) for premenopausal breast cancer associated with beginning
      smoking before age 18 together with accumulation of >=20 pack years. The positive
      association with premenopausal breast cancer was most apparent for estrogen
      receptor-positive cancer. Passive smoking was also associated with increased risk
      of premenopausal breast cancer (IRR = 1.42, 95 % CI 1.09-1.85), based on
      information on passive smoking at home and work. Neither active nor passive
      smoking was associated with increased risk of postmenopausal breast cancer.
      CONCLUSION: These results strengthen the evidence that both active and passive
      smoking increase the incidence of premenopausal breast cancer.

PMID- 24085587
TI  - Pulmonary alveolar microlithiasis: imaging characteristics of planar and SPECT/CT
      bone scan versus 18F-FDG and 18F-sodium fluoride PET/CT scanning.
AB  - Pulmonary alveolar microlithiasis (PAM) is a very rare disease in which multiple
      microscopic calcium phosphate microliths are deposited within the alveoli of both
      lungs. A lung biopsy is considered to be definitive for final diagnosis; however,
      non-invasive imaging modalities such as chest X-ray, HRCT scan and (99m)Tc-MDP
      bone scan suggest the diagnosis in the vast majority of patients. Although (18)F
      FDG PET/CT has been tried to characterize the disease, (18)F-sodium fluoride
      PET/CT as a 'proof-of-principle' was tried for the first time in a known case of
      PAM in order to characterize the lung lesions. Interestingly, we noted that (18)F
      sodium fluoride PET/CT is a superior modality in characterization and assessment
      of the extent of disease in PAM compared to all other non-invasive imaging
      modalities. Thus, we recommend that (18)F-sodium fluoride PET/CT should be the
      investigation of choice in PAM. 

PMID- 24085588
TI  - Extracellular Hsp72 concentration relates to a minimum endogenous criteria during
      acute exercise-heat exposure.
AB  - Extracellular heat shock protein 72 (eHsp72) concentration increases during
      exercise-heat stress when conditions elicit physiological strain. Differences in
      severity of environmental and exercise stimuli have elicited varied response to
      stress. The present study aimed to quantify the extent of increased eHsp72 with
      increased exogenous heat stress, and determine related endogenous markers of
      strain in an exercise-heat model. Ten males cycled for 90 min at 50 % [Formula:
      see text] in three conditions (TEMP, 20  degrees C/63 % RH; HOT, 30.2  degrees
      C/51%RH; VHOT, 40.0  degrees C/37%RH). Plasma was analysed for eHsp72 pre,
      immediately post and 24-h post each trial utilising a commercially available
      ELISA. Increased eHsp72 concentration was observed post VHOT trial (+172.4 %) (p
      < 0.05), but not TEMP (-1.9 %) or HOT (+25.7 %) conditions. eHsp72 returned to
      baseline values within 24 h in all conditions. Changes were observed in rectal
      temperature (Trec), rate of Trec increase, area under the curve for Trec of 38.5
      and 39.0  degrees C, duration Trec >=38.5 and >=39.0  degrees C, and change in
      muscle temperature, between VHOT, and TEMP and HOT, but not between TEMP and HOT.
      Each condition also elicited significantly increasing physiological strain,
      described by sweat rate, heart rate, physiological strain index, rating of
      perceived exertion and thermal sensation. Stepwise multiple regression reported
      rate of Trec increase and change in Trec to be predictors of increased eHsp72
      concentration. Data suggests eHsp72 concentration increases once systemic
      temperature and sympathetic activity exceeds a minimum endogenous criteria
      elicited during VHOT conditions and is likely to be modulated by large, rapid
      changes in core temperature.

PMID- 24085589
TI  - Adding pregabalin or gabapentin for the management of community-treated patients
      with painful diabetic peripheral neuropathy: a comparative cost analysis.
AB  - BACKGROUND AND OBJECTIVE: Painful diabetic peripheral neuropathy (pDPN) is a
      highly prevalent complication of diabetes mellitus, which is associated with
      substantial costs to society and national health systems. This economic impact
      varies depending on the therapeutic management provided to patients. The
      objective of this study was to compare healthcare resource utilization and costs
      among pDPN patients newly treated with pregabalin or gabapentin in routine
      medical practice. METHODS: We performed a retrospective medical records study of
      pDPN patients newly treated with pregabalin or gabapentin as an add-on therapy
      who are covered by the Badalona Serveis Assistencials (BSA) health plan, a
      healthcare provider in Spain, from 2006 to 2009. Healthcare resource utilization
      and days off work were assessed. The societal perspective was used to estimate
      costs. RESULTS: Three hundred and ninety-five records were eligible for analysis:
      227 (57.5%) included pregabalin and 168 (42.5%) gabapentin. Mean (standard
      deviation) concomitant use of analgesics throughout the study was higher in the
      gabapentin cohort [3.9 (2.2) vs. 3.1 (2.1); p < 0.05], mainly due to greater use
      of non-narcotics (78.0 vs. 71.8%; p < 0.05) and opioids (32.7 vs. 28.6%; p <
      0.05). Healthcare costs accounted for 59.2% of total costs, of which 71.9%
      occurred in primary care, with a mean cost per patient of ?2,476 (year 2010
      values). Adjusted mean (95% CI) total costs were significantly lower in
      pregabalin-treated patients [?2,003 (1,427-2,579)] than in gabapentin-treated
      patients [?3,127 (2,463-3,790)] (p = 0.013), mainly due to lower healthcare costs
      [?1,312 (1,192-1,432) vs. ?1,675 (1,537-1,814); p < 0.001]. CONCLUSIONS: Adding
      pregabalin to existing pDPN therapy resulted in lower total healthcare costs and
      lower resource utilization than resulted from adding gabapentin.

PMID- 24085590
TI  - Pharmacokinetic characterization of tizanidine nasal spray, a novel intranasal
      delivery method for the treatment of skeletal muscle spasm.
AB  - BACKGROUND AND OBJECTIVE: The skeletal muscle relaxant tizanidine is approved by
      the US FDA and the European Medicines Agency for treating spasticity and is
      supplied as tablets for oral administration. However, tizanidine has a poor
      bioavailability, due to extensive first-pass metabolism. Therefore, the nasal
      route of administration, which bypasses portal circulation, may increase the
      bioavailability of tizanidine and, possibly, reduce the time to peak plasma
      concentration, thereby shorting the latency of therapeutic effect. The objective
      of this study was to evaluate the pharmacokinetic profile of tizanidine nasal
      spray and compare it to the profile of tizanidine oral tablets. METHODS: This
      open-label, phase I study comprised two protocols: protocol 1, tizanidine HCl
      solution (32.73 mg/mL) intranasally at single doses of 2 and 4 mg versus 4 mg
      tizanidine oral tablets (randomized, three periods crossover, 12 healthy
      subjects); and protocol 2, tizanidine HCl solution (16.36 mg/mL) intranasally at
      a single dose of 1 mg vs. 4 mg tizanidine oral tablets (randomized, two periods
      crossover, 12 healthy subjects, one dropout). Tizanidine plasma concentrations
      were determined by liquid chromatography/mass spectrometry. RESULTS: There was a
      linear relationship between different dosages of intranasal formulation and the
      area under the concentration-time curve and maximum plasma concentration
      (C(max)). The relative bioavailability of the different dosages of intranasal
      formulation were 1.29, 1.93, and 4.23 for 1, 2, and 4 mg intranasal
      administration, respectively. Comparison of C(max) values gave the following
      ratios: 0.91, 1.39, and 2.73, for 1, 2, and 4 mg intranasal administration,
      respectively. The mean time to C(max) (t(max)) was 0.99, 0.43, and 0.63 h for 1,
      2, and 4 mg intranasal administration, respectively, whereas it was 1.13 and 1.30
      h for the two series of 4 mg tizanidine oral tablets. CONCLUSIONS: The
      bioavailability of the tizanidine intranasal formulation was higher than that of
      tizanidine oral tablets. The t(max) was also shorter with the intranasal
      formulation. No serious adverse events occurred throughout the study, such that
      the two formulations resulted equally well-tolerated. The intranasal formulation
      of tizanidine results are therefore worthy of subsequent clinical testing in
      phase II.

PMID- 24085591
TI  - ACCORD COPD II: a randomized clinical trial to evaluate the 12-week efficacy and
      safety of twice-daily aclidinium bromide in chronic obstructive pulmonary disease
      patients.
AB  - BACKGROUND AND OBJECTIVES: Aclidinium bromide is a long-acting muscarinic
      antagonist approved for the long-term maintenance treatment of bronchospasm
      associated with chronic obstructive pulmonary disease (COPD). This 12-week phase
      III study evaluated efficacy and tolerability of aclidinium 200 or 400 MUg in
      patients with moderate-to-severe COPD. METHODS: In this double-blind study, 544
      patients with COPD were randomized to placebo or twice-daily aclidinium 200 or
      400 MUg administered by Genuair((r))/Pressair((r)). Lung function, health status
      [measured by the St. George's Respiratory Questionnaire (SGRQ)], dyspnea
      [measured using the Transition Dyspnea Index (TDI)], and safety were assessed
      throughout the study. RESULTS: Mean changes from baseline in morning trough
      forced expiratory volume in 1 s (FEV(1)) at week 12 (primary endpoint) were
      significantly higher for aclidinium than for placebo (200 MUg, 51 mL; 400 MUg, 72
      mL; both p < 0.05). Aclidinium also significantly improved other lung function
      outcomes. At week 12, improvements from baseline were observed with aclidinium in
      SGRQ total score (200 MUg, -6.0; 400 MUg, -5.4) and TDI focal score (200 MUg,
      1.0; 400 MUg, 1.3). Furthermore, clinically important improvements in SGRQ total
      and TDI focal scores were achieved by 45 and 51 % of patients, respectively, who
      received aclidinium 400 MUg, with a significant difference versus placebo for TDI
      (p < 0.05). Anticholinergic-related adverse events (e.g., dry mouth) were
      infrequent, occurring <2 % for any event in any treatment group. Both aclidinium
      doses were well tolerated. CONCLUSION: This study demonstrates efficacy and
      safety of aclidinium in COPD patients. Unexpected baseline imbalances between
      treatment groups may have impacted the aclidinium treatment benefit in this
      study.

PMID- 24085592
TI  - Face-to-face interventions for promoting physical activity.
AB  - BACKGROUND: Face-to-face interventions for promoting physical activity (PA) are
      continuing to be popular but their ability to achieve long term changes are
      unknown. OBJECTIVES: To compare the effectiveness of face-to-face interventions
      for PA promotion in community dwelling adults (aged 16 years and above) with a
      control exposed to placebo or no or minimal intervention. SEARCH METHODS: We
      searched CENTRAL, MEDLINE, EMBASE, CINAHL, and some other databases (from
      earliest dates available to October 2012). Reference lists of relevant articles
      were checked. No language restrictions were applied. SELECTION CRITERIA:
      Randomised controlled trials (RCTs) that compared face-to-face PA interventions
      for community dwelling adults with a placebo or no or minimal intervention
      control group. We included studies if the principal component of the intervention
      was delivered using face-to-face methods. To assess behavioural change over time
      the included studies had a minimum of 12 months follow-up from the start of the
      intervention to the final results. We excluded studies that had more than a 20%
      loss to follow-up if they did not apply an intention-to-treat analysis. DATA
      COLLECTION AND ANALYSIS: At least two authors independently assessed the quality
      of each study and extracted data. Non-English language papers were reviewed with
      the assistance of an interpreter who was an epidemiologist. Study authors were
      contacted for additional information where necessary. Standardised mean
      differences (SMDs) and 95% confidence intervals (CIs) were calculated for
      continuous measures of self-reported PA and cardio-respiratory fitness. For
      studies with dichotomous outcomes, odds ratios (ORs) and 95% CIs were calculated.
      MAIN RESULTS: A total of 10 studies recruiting 6292 apparently healthy adults met
      the inclusion criteria. All of the studies took place in high-income countries.
      The effect of interventions on self-reported PA at one year (eight studies; 6725
      participants) was positive and moderate with significant heterogeneity (I2 = 74%)
      (SMD 0.19; 95% CI 0.06 to 0.31; moderate quality evidence) but not sustained in
      three studies at 24 months (4235 participants) (SMD 0.18; 95% CI -0.10 to 0.46).
      The effect of interventions on cardiovascular fitness at one year (two studies;
      349 participants) was positive and moderate with no significant heterogeneity in
      the observed effects (SMD 0.50; 95% CI 0.28 to 0.71; moderate quality evidence).
      Three studies (3277 participants) reported a positive effect on increasing PA
      levels when assessed as a dichotomous measure at 12 months, but this was not
      statistically significant (OR 1.52; 95% CI 0.88 to 2.61; high quality evidence).
      Although there were limited data, there was no evidence of an increased risk of
      adverse events (one study; 149 participants). Risk of bias was assessed as low
      (four studies; 4822 participants) or moderate (six studies; 1543 participants).
      Any conclusions drawn from this review require some caution given the significant
      heterogeneity in the observed effects. Despite this, there was some indication
      that the most effective interventions were those that offered both individual and
      group support for changing PA levels using a tailored approach. The long term
      impact, cost effectiveness and rates of adverse events for these interventions
      was not established because the majority of studies stopped after 12 months.
      AUTHORS' CONCLUSIONS: Although we found evidence to support the effectiveness of
      face-to-face interventions for promoting PA, at least at 12 months, the
      effectiveness of these interventions was not supported by high quality studies.
      Due to the clinical and statistical heterogeneity of the studies, only limited
      conclusions can be drawn about the effectiveness of individual components of the
      interventions. Future studies should provide greater detail of the components of
      interventions, and assess impact on quality of life, adverse events and economic
      data.

PMID- 24085593
TI  - Face-to-face versus remote and web 2.0 interventions for promoting physical
      activity.
AB  - BACKGROUND: Face-to-face interventions for promoting physical activity (PA) are
      continuing to be popular as remote and web 2.0 approaches rapidly emerge, but we
      are unsure which approach is more effective at achieving long term sustained
      change. OBJECTIVES: To compare the effectiveness of face-to-face versus remote
      and web 2.0 interventions for PA promotion in community dwelling adults (aged 16
      years and above). SEARCH METHODS: We searched CENTRAL, MEDLINE, EMBASE, CINAHL,
      and some other databases (from earliest dates available to October 2012).
      Reference lists of relevant articles were checked. No language restrictions were
      applied. SELECTION CRITERIA: Randomised trials that compared face-to-face versus
      remote and web 2.0 PA interventions for community dwelling adults. We included
      studies if they compared an intervention that was principally delivered face-to
      face to an intervention that had principally remote and web 2.0 methods. To
      assess behavioural change over time, the included studies had a minimum of 12
      months follow-up from the start of the intervention to the final results. We
      excluded studies that had more than a 20% loss to follow-up if they did not apply
      an intention-to-treat analysis. DATA COLLECTION AND ANALYSIS: At least two review
      authors independently assessed the quality of each study and extracted the data.
      Non-English language papers were reviewed with the assistance of an interpreter
      who was an epidemiologist. Study authors were contacted for additional
      information where necessary. Standardised mean differences (SMDs) and 95%
      confidence intervals (CIs) were calculated for continuous measures of cardio
      respiratory fitness. MAIN RESULTS: One study recruiting 225 apparently healthy
      adults met the inclusion criteria. This study took place in a high-income
      country. From 27,299 hits, the full texts of 193 papers were retrieved for
      examination against the inclusion criteria. However, there was only one paper
      that met the inclusion criteria. This study reported the effect of a PA
      intervention on cardio-respiratory fitness. There were no reported data for PA,
      quality of life, or cost effectiveness. The difference between the remote and web
      2.0 versus face-to-face arms was not significant (SMD -0.02; 95% CI -0.30 to
      0.26; high quality evidence). The risk of bias in the included study was assessed
      as low, and there was no evidence of an increased risk of adverse events.
      AUTHORS' CONCLUSIONS: There is insufficient evidence to assess whether face-to
      face interventions or remote and web 2.0 approaches are more effective at
      promoting PA.

PMID- 24085594
TI  - Remote and web 2.0 interventions for promoting physical activity.
AB  - BACKGROUND: Remote and web 2.0 interventions for promoting physical activity (PA)
      are becoming increasingly popular but their ability to achieve long term changes
      are unknown. OBJECTIVES: To compare the effectiveness of remote and web 2.0
      interventions for PA promotion in community dwelling adults (aged 16 years and
      above) with a control group exposed to placebo or no or minimal intervention.
      SEARCH METHODS: We searched CENTRAL, MEDLINE, EMBASE, CINAHL, and some other
      databases (from earliest dates available to October 2012). Reference lists of
      relevant articles were checked. No language restrictions were applied. SELECTION
      CRITERIA: Randomised controlled trials (RCTs) that compared remote and web 2.0 PA
      interventions for community dwelling adults with a placebo or no or minimal
      intervention control group. We included studies if the principal component of the
      intervention was delivered using remote or web 2.0 technologies (for example the
      internet, smart phones) or more traditional methods (for example telephone, mail
      outs), or both. To assess behavioural change over time, the included studies had
      a minimum of 12 months follow-up from the start of the intervention to the final
      results. We excluded studies that had more than a 20% loss to follow-up if they
      did not apply an intention-to-treat analysis. DATA COLLECTION AND ANALYSIS: At
      least two authors independently assessed the quality of each study and extracted
      the data. Non-English language papers were reviewed with the assistance of an
      interpreter who was an epidemiologist. Study authors were contacted for
      additional information where necessary. Standardised mean differences (SMDs) and
      95% confidence intervals (CIs) were calculated for the continuous measures of
      self-reported PA and cardio-respiratory fitness. For studies with dichotomous
      outcomes, odds ratios and 95% CIs were calculated. MAIN RESULTS: A total of 11
      studies recruiting 5862 apparently healthy adults met the inclusion criteria. All
      of the studies took place in high-income countries. The effect of the
      interventions on cardiovascular fitness at one year (two studies; 444
      participants) was positive and moderate with significant heterogeneity of the
      observed effects (SMD 0.40; 95% CI 0.04 to 0.76; high quality evidence). The
      effect of the interventions on self-reported PA at one year (nine studies; 4547
      participants) was positive and moderate (SMD 0.20; 95% CI 0.11 to 0.28; moderate
      quality evidence) with heterogeneity (I2 = 37%) in the observed effects. One
      study reported positive results at two years (SMD 0.20; 95% CI 0.08 to 0.32;
      moderate quality evidence). When studies were stratified by risk of bias, the
      studies at low risk of bias (eight studies; 3403 participants) had an increased
      effect (SMD 0.28; 95% CI 0.16 to 0.40; moderate quality evidence). The most
      effective interventions applied a tailored approach to the type of PA and used
      telephone contact to provide feedback and to support changes in PA levels. There
      was no evidence of an increased risk of adverse events (seven studies; 2892
      participants). Risk of bias was assessed as low (eight studies; 3060
      participants) or moderate (three studies; 2677 participants). There were no
      differences in effectiveness between studies using different types of
      professionals delivering the intervention (for example health professional,
      exercise specialist). There was no difference in pooled estimates between studies
      that generated the prescribed PA using an automated computer programme versus a
      human, nor between studies that used pedometers as part of their intervention
      compared to studies that did not. AUTHORS' CONCLUSIONS: We found consistent
      evidence to support the effectiveness of remote and web 2.0 interventions for
      promoting PA. These interventions have positive, moderate sized effects on
      increasing self-reported PA and measured cardio-respiratory fitness, at least at
      12 months. The effectiveness of these interventions was supported by moderate and
      high quality studies. However, there continues to be a paucity of cost
      effectiveness data and studies that include participants from varying
      socioeconomic or ethnic groups. To better understand the independent effect of
      individual programme components, longer term studies, with at least one year
      follow-up, are required.

PMID- 24085595
TI  - Thermal relaxation times: an outdated concept in photothermal treatments.
AB  - Thermal relaxation times were introduced into modern skin-laser science with the
      inception of selective photothermolysis. As a result, laser pulsewidths were
      determined according to the thermal relaxation times of the tissue targets. The
      Arrhenius Damage Integral shows that this approach is incorrect. The important
      parameter is the time required to induce irreversible protein denaturation within
      the target. This time is determined by the tissue's intrinsic structure, not its
      physical dimensions. This report explains why thermal relaxation times should not
      be considered when treating many skin conditions with lasers or IPL systems. 

PMID- 24085596
TI  - Sieve estimation in semiparametric modeling of longitudinal data with informative
      observation times.
AB  - Analyzing irregularly spaced longitudinal data often involves modeling possibly
      correlated response and observation processes. In this article, we propose a new
      class of semiparametric mean models that allows for the interaction between the
      observation history and covariates, leaving patterns of the observation process
      to be arbitrary. For inference on the regression parameters and the baseline mean
      function, a spline-based least squares estimation approach is proposed. The
      consistency, rate of convergence, and asymptotic normality of the proposed
      estimators are established. Our new approach is different from the usual
      approaches relying on the model specification of the observation scheme, and it
      can be easily used for predicting the longitudinal response. Simulation studies
      demonstrate that the proposed inference procedure performs well and is more
      robust. The analyses of bladder tumor data and medical cost data are presented to
      illustrate the proposed method. 

PMID- 24085597
TI  - Surgery for traumatic facial nerve paralysis: does intraoperative monitoring have
      a role?
AB  - The use of intraoperative facial nerve (FN) monitoring during surgical
      decompression of the FN is underscored because surgery is indicated when the FN
      shows more than 90 % axonal degeneration. The present study proposes including
      intraoperative monitoring to facilitate decision taking and provide
      prognostication with more accuracy. This prospective study was conducted on ten
      patients presenting with complete FN paralysis due to temporal bone fracture.
      They were referred after variable time intervals for FN exploration and
      decompression. Intraoperative supramaximal electric stimulation (2-3 mA) of the
      FN was attempted in all patients both proximal and distal to the site of injury.
      Postoperative FN function was assessed using House-Brackmann (HB) scale. All
      patients had follow-up period ranging from 7 to 42 months. Three different
      patterns of neurophysiological responses were characterized. Responses were
      recorded proximal and distal to the lesion in five patients (pattern 1); only
      distal to the lesion in two patients (pattern 2); and neither proximal nor distal
      to the lesion in three patients (pattern 3). Sporadic, mechanically elicited EMG
      activity was recorded in eight out of ten patients. Patients with pattern 1 had
      favorable prognosis with postoperative function ranging between grade I and III.
      Pattern 3 patients showing no mechanically elicited activity had poor prognosis.
      Intraoperative monitoring affects decision taking during surgery for traumatic FN
      paralysis and provides prognostication with sufficient accuracy. The detection of
      mechanically elicited EMG activity is an additional sign predicting favorable
      outcome. However, absence of responses did not alter surgeon decision when the
      nerve was found evidently intact.

PMID- 24085598
TI  - Impact of chemotherapy and radiotherapy in childhood on fertility in adulthood:
      the FeCt-survey of childhood cancer survivors in Germany.
AB  - PURPOSE: Improved treatment for childhood cancer has led to better survival rates
      of 83 % today. However, long-term side effects including infertility of pediatric
      patients receiving oncologic treatment remain unclear. We examined the
      association of chemotherapy and radiotherapy with infertility in survivors of
      pediatric cancer. METHODS: A questionnaire on fertility was sent to adult
      survivors listed in the German Childhood Cancer Registry. Fertility status was
      defined based on information on attempts to conceive, pregnancies, births,
      menstrual cycle and previous fertility test results. RESULTS: Therapeutic data
      were obtained from treatment optimization trials. We included 618 childhood
      cancer survivors (384 women) who reported information allowing us to classify
      their current fertility status as 'fertile/probably fertile' or 'probably
      infertile'. Thirty-one percent of 83 female and 29 % of 117 male survivors
      reported infertility based on previous fertility tests. 'Probably infertile'
      adult survivors were more likely to have received pelvic radiotherapy (women:
      adjusted OR 20.24, 95 % CI 4.69-87.29; men: 12.22; 1.18-126.70) than those who
      were 'fertile/probably fertile'. Etoposide, particularly >=5,000 mg/m(2) in
      women, and carboplatin and/or cisplatin in both sexes seemed to have independent
      risk potential for infertility. Similarly, cancer treatment during or post
      puberty compared to treatment before puberty showed a trend toward increased
      infertility, particularly in male survivors. CONCLUSIONS: Patients and families
      need to be informed about fertility-preserving measures prior to and also after
      chemotherapy and radiotherapy.

PMID- 24085599
TI  - Percutaneous image-guided biopsy of prostate cancer metastases yields samples
      suitable for genomics and personalised oncology.
AB  - Personalised oncology through mutational profiling of cancers requires the
      procurement of fresh frozen tumour samples for genomics applications. While
      primary cancers are often surgically excised and therefore yield such tissue,
      metastases in the setting of a known cancer diagnosis are not routinely sampled
      prior to systemic therapy. Our study aimed to determine the suitability of
      extracted nucleic acids for genomics applications using distant metastatic
      prostate cancer samples obtained via percutaneous or surgical biopsy. Patients
      with metastatic prostate cancer were recruited for image-guided biopsy of
      metastases. Patients undergoing surgical procedures for the complications of
      metastases were also recruited. Tissue samples were flash frozen and
      cryosectioned for histological examination. DNA and RNA were simultaneously
      extracted and genomic DNA hybridised onto SNP arrays for genome-wide copy number
      analysis. 37 samples of metastatic tissue from seven patients with prostate
      cancer were obtained. Five of these underwent image-guided biopsies whilst two
      had therapeutic surgical procedures performed. 22 biopsy samples were obtained
      across the image-guided biopsy patients with 80 % of samples being successfully
      processed for downstream analysis. Nucleic acid yield from these samples were
      satisfactory for genomics applications. Copy number analysis revealed a median
      estimated tumour purity of 53 % and all samples showed chromosomal abnormalities
      suggestive of malignancy. The procurement of osseous metastatic prostate cancer
      from live patients, including the use of image-guided biopsy, is safe and
      feasible. Sufficient tissue can be obtained in a manner such that extracted
      nucleic acids are suitable for genomics research.

PMID- 24085600
TI  - Random-effects linear modeling and sample size tables for two special crossover
      designs of average bioequivalence studies: the four-period, two-sequence, two
      formulation and six-period, three-sequence, three-formulation designs.
AB  - Due to concern and debate in the epilepsy medical community and to the current
      interest of the US Food and Drug Administration (FDA) in revising approaches to
      the approval of generic drugs, the FDA is currently supporting ongoing
      bioequivalence studies of antiepileptic drugs, the EQUIGEN studies. During the
      design of these crossover studies, the researchers could not find commercial or
      non-commercial statistical software that quickly allowed computation of sample
      sizes for their designs, particularly software implementing the FDA requirement
      of using random-effects linear models for the analyses of bioequivalence studies.
      This article presents tables for sample-size evaluations of average
      bioequivalence studies based on the two crossover designs used in the EQUIGEN
      studies: the four-period, two-sequence, two-formulation design, and the six
      period, three-sequence, three-formulation design. Sample-size computations assume
      that random-effects linear models are used in bioequivalence analyses with
      crossover designs. Random-effects linear models have been traditionally viewed by
      many pharmacologists and clinical researchers as just mathematical devices to
      analyze repeated-measures data. In contrast, a modern view of these models
      attributes an important mathematical role in theoretical formulations in
      personalized medicine to them, because these models not only have parameters that
      represent average patients, but also have parameters that represent individual
      patients. Moreover, the notation and language of random-effects linear models
      have evolved over the years. Thus, another goal of this article is to provide a
      presentation of the statistical modeling of data from bioequivalence studies that
      highlights the modern view of these models, with special emphasis on power
      analyses and sample-size computations. 

PMID- 24085601
TI  - The TPO/c-MPL pathway in the bone marrow may protect leukemia cells from
      chemotherapy in AML Patients.
AB  - Accumulating evidence indicates that the interaction of human LSCs (leukemic stem
      cells) with the hematopoietic microenvironment, mediated by the thrombopoietin
      (TPO)/c-MPL pathway, may be an underlying mechanism for resistance to cell cycle
      dependent cytotoxic chemotherapy. However, the role of TPO/c-MPL signaling in AML
      (acute myelogenous leukemia) chemotherapy resistance hasn't been fully
      understood. The c-MPL and TPO levels in different AML samples were measured by
      flow cytometry and ELISA. We also assessed the TPO levels in the osteoblasts
      derived from bone mesenchymal stem cells (BMSCs). The survival rate of an AML
      cell line that had been co-cultured with different BMSC-derived osteoblasts was
      measured to determine the IC50 of an AML chemotherapy drug daunorubicin (DNR).
      The levels of TPO/c-MPL in the initial and relapse AML patients were
      significantly higher than that in the control (P < 0.05). The osteoblasts derived
      from AML patients' BMSCs secreted more TPO than the osteoblasts derived from
      normal control BMSCs (P < 0.05). A strong positive correlation between the TPO
      level and c-MPL expression was found in the bone marrow mononuclear cells of the
      relapse AML patients. More importantly, the IC50 of DNR in the HEL + AML-derived
      osteoblasts was the highest among all co-culture systems. High level of TPO/c-MPL
      signaling may protect LSCs from chemotherapy in AML. The effects of inhibition of
      the TPO/c-MPL pathway on enhancing the chemotherapy sensitivity of AML cells, and
      on their downstream effector molecules that direct the interactions between
      patient-derived blasts and leukemia repopulating cells need to be further
      studied.

PMID- 24085602
TI  - Heavy metal bioaccumulation and antioxidative responses in Cardaminopsis arenosa
      and Plantago lanceolata leaves from metalliferous and non-metalliferous sites: a
      field study.
AB  - The purpose of this study was to determine the concentrations of heavy metals
      (cadmium, lead, zinc, copper, iron and manganese) in soil, their bioavailability
      and bioaccumulation in plants leaves. This study also examined their influences
      on the antioxidant response of the plants Cardaminopsis arenosa and Plantago
      lanceolata grown in metal-contaminated and non-contaminated soils. The activities
      of guaiacol peroxidase and superoxide dismutase and the levels of antioxidants
      such as glutathione, proline and non-protein thiols were measured. Concentrations
      of the examined metals were several to thousands of times lower in the
      potentially bioavailable fraction than in the acid-extracted fraction of the
      soil. Similar mode of antioxidant responses in plant leaves of metalliferous
      populations indicates the tolerance of plants towards heavy metals. However POD
      and GSHt had a particularly strong role in defense reactions, as their increase
      was the most common reaction to heavy metal contamination.The levels of Zn, Cd
      and Pb in the leaves of C. arenosa better reflected metal concentrations in the
      metalliferous and non-metalliferous soil than the determined metal concentrations
      in P. lanceolata. Bioaccumulated Zn, Cd and Pb concentrations were above or in
      the ranges mentioned as toxic for plant tissues and therefore the studied plants
      have potential for use in phytostabilization. 

PMID- 24085603
TI  - Mercury, pets' and hair: baseline survey of a priority environmental pollutant
      using a noninvasive matrix in man's best friend.
AB  - Pet cats and dogs have been successfully used as indicators of environmental
      pollution by a great variety of chemicals, including metals. However, information
      on mercury (a well know priority environmental pollutant) concentrations in
      household pets tissues and/or organs is scarce. Thus, in the present work we
      quantified total mercury (Hg(Total)) in blood and hair samples from twenty-six
      household dogs. The obtained results disclose relatively low levels of total
      mercury in the surveyed dogs, with values ranging from 0.16 to 12.38 ng g(-1) in
      blood; and from 24.16 to 826.30 ng g(-1) in hair. Mercury concentrations were
      independent of gender, age and diet type. A highly significant positive
      correlation was established between total mercury in blood and hair, validating
      the latter as a surrogate, non-invasive matrix for mercury exposure evaluation.
      Additionally, the obtained blood to hair ratio (200) is similar to the one
      described for humans reinforcing the suitability of dogs as sentinels. Overall,
      the determination of total mercury levels in dogs' hair samples proved to be a
      good screening method for the estimation of mercury burden in this species. We
      propose the quantification of Hg(Total) in hair as a screening method for
      sentinels like household pets to be performed in routine veterinary visits.

PMID- 24085604
TI  - Toxicity and critical body residues of Cd, Cu and Cr in the aquatic oligochaete
      Tubifex tubifex (Muller) based on lethal and sublethal effects.
AB  - The aim of the present study was to estimate critical body residues (CBRs) of
      three metals [cadmium (Cd), copper (Cu), chromium (Cr)] in the aquatic
      oligochaete Tubifex tubifex based on lethal (LBR) and sublethal effects (CBR),
      and to discuss the relevance of the exposure to sediment for deriving CBR.
      Toxicity parameters (LC50, EC50, LBR50 and CBR50) were estimated for each metal
      by means of data on survival and on several sublethal variables measured in short
      term (4 days), water-only exposures and in long-term, chronic (14 and 28 days)
      exposures using metal-spiked sediment. Sublethal endpoints included autotomy in
      short-term exposure, as well as reproduction and growth in chronic bioassays.
      LBR50 and CBR50 were 3-6 times higher in sediment than in water-only exposure to
      Cd and about 2-11 times higher for Cu, depending on the measured endpoint;
      however, for Cr these parameters varied only by a factor of 1.2. Cu and Cr LBR50
      and CBR50 values in 96 h water-only exposure were very similar (survival 2.39
      MUmol Cu g(-1) dw, 2.73 MUmol Cr g(-1) dw; autotomy 0.53 MUmol Cu g(-1) dw, 0.78
      MUmol Cr g(-1) dw). However, in metal-spiked sediments, 28 d CBR50 values for
      autotomy, reproduction and growth ranged 6.76-29.54 MUmol g(-1) dw for Cd, 3.88
      6.23 MUmol g(-1) dw for Cu, 0.65 MUmol g(-1) dw for Cr (calculated only on total
      number of young). Exposure conditions (time and presence/absence of sediment)
      seem to be influential in deriving metal CBR values of Cd and Cu, while appear to
      be irrelevant for Cr. Thus, CBR approach for metals is complex and tissue residue
      toxicity relationship is not directly applicable so far.

PMID- 24085605
TI  - Endocrine disruption of sexual selection by an estrogenic herbicide in the
      mealworm beetle (Tenebrio molitor).
AB  - The role that endocrine disruption could play in sexual selection remains
      relatively untested, and although estrogens occur in insects, little information
      exists about their biological role in insect reproduction. Atrazine is a commonly
      applied herbicide that mimics estrogen in vertebrates. Tenebrio molitor were
      raised from egg to adult under a gradation of environmentally relevant atrazine
      exposures and a non-treated control. Atrazine was delivered in the drinking water
      ad libitum. Female T. molitor were provided with a choice between unrelated males
      raised under three levels of atrazine exposures. Female preference for males
      demonstrated a non-monotonic inverted U-shaped response to atrazine exposure.
      There was no significant difference between the control and the high exposure to
      atrazine. Excluding the control, female preference increased as exposure
      concentration increased. These results have important repercussions for nonlethal
      effects of endocrine disruption on populations, their capacity to interfere with
      sexual selection, and the role of estrogen in pheromone communication among
      insects. 

PMID- 24085606
TI  - Impact of chemical- and bio-pesticides on bacterial diversity in rhizosphere of
      Vigna radiata.
AB  - To study the effects of two chemical pesticides (chlorpyrifos and endosulfan),
      and a bio-pesticide (azadirachtin) on bacterial diversity in rhizospheric soil, a
      randomized pot experiment was conducted on mung bean (Vigna radiata) with
      recommended and higher doses of pesticides. Denaturing gradient gel
      electrophoresis was used to analyze such effects on both resident and active
      bacterial communities across two time points. It was observed that higher doses
      of azadirachtin mimicked the effects of chlorpyrifos on bacterial diversity. Both
      azadirachtin and chlorpyrifos showed a dose- and time-dependent effect, which was
      observable only at the RNA level. Endosulfan treatments showed dissimilar
      profiles compared to control. Most of the bands showed high sequence similarities
      to known bacterial groups, including many nitrogen-fixing, phosphate
      solubilizing, and plant-growth-promoting bacteria. This study indicates that
      pesticides display non-target effects on active microbial populations that serve
      important ecosystem functions, thereby emphasizing the need to critically
      investigate and validate the use of bio-pesticides in agriculture before
      accepting them as safe alternatives to chemical pesticides. 

PMID- 24085607
TI  - Heritable targeted inactivation of the rainbow trout (Oncorhynchus mykiss) master
      sex-determining gene using zinc-finger nucleases.
AB  - Gene targeting is a powerful tool for analyzing gene function. Recently, new
      technology for gene targeting using engineered zinc-finger nucleases (ZFNs) has
      been described in fish species. However, it has not yet been widely used for cold
      water and slow developing species, such as Salmonidae. Here, we present the
      results of successful ZFN-mediated disruption of the sex-determining gene sdY
      (sexually dimorphic on the Y chromosome) in rainbow trout (Oncorhynchus mykiss).
      Three pairs of ZFN mRNA targeted to different regions of the sdY gene were
      injected into fertilized rainbow trout eggs. Sperm from 1-year-old male founders
      (parental generation one or P1) carrying a ZFN-induced mutation in their germline
      were then used to produce F1 non-mosaic animals. In these F1 populations, we
      characterized 14 different mutations in the sdY gene, including one mutation
      leading to the deletion of leucine 43 (L43) and 13 mutations at other target
      sites that had different effects on the SdY protein, i.e., amino acid insertions,
      deletions, and frameshift mutations producing premature stop codons in the mRNA.
      The gonadal phenotype analysis of the F1-mutated animals revealed that the single
      L43 amino acid deletion did not lead to a male-to-female sex reversal, but all
      other mutations induced a clear ovarian phenotype. These results show that
      targeted gene disruption using ZFN is efficient in rainbow trout but depends on
      the ZFN design. We also characterized new sdY mutations resulting in male-to
      female sex reversal, and we conclude that L43 seems dispensable for SdY function.

PMID- 24085608
TI  - Production of homozygous transgenic rainbow trout with enhanced disease
      resistance.
AB  - Previous studies conducted in our laboratory showed that transgenic medaka
      expressing cecropin B transgenes exhibited resistant characteristic to fish
      bacterial pathogens, Pseudomonas fluorescens and Vibrio anguillarum. To confirm
      whether antimicrobial peptide gene will also exhibit anti-bacterial and anti
      viral characteristics in aquaculture important fish species, we produced
      transgenic rainbow trout expressing cecropin P1 or a synthetic cecropin B analog,
      CF-17, transgene by sperm-mediated gene transfer method. About 30 % of fish
      recovered from electroporation were shown to carry the transgene as determined by
      polymerase chain reaction (PCR) amplification assay. Positive P1 transgenic fish
      were crossed to non-transgenic fish to establish F1 transgenic founder families,
      and subsequently generating F2, and F3 progeny. Expression of cecropin P1 and CF
      17 transgenes was detected in transgenic fish by reverse transcription (RT)-PCR
      analysis. The distribution of body sizes among F1 transgenic fish were not
      significantly different from those of non-transgenic fish. Results of challenge
      studies revealed that many families of F2 and F3 transgenic fish exhibited
      resistance to infection by Aeromonas salmonicida and infectious hematopoietic
      necrosis virus (IHNV). All-male homozygous cecropin P1 transgenic families were
      produced by androgenesis from sperm of F3 heterozygous transgenic fish in one
      generation. The resistant characteristic to A. salmonicida was confirmed in
      progeny derived from the outcross of all-male fish to non-transgenic females.
      Results of our current studies confirmed the possibility of producing disease
      resistant homozygous rainbow trout strains by transgenesis of cecropin P1 or CF
      17 gene and followed by androgenesis.

PMID- 24085609
TI  - Verbal working memory impairments following traumatic brain injury: an fNIRS
      investigation.
AB  - The construct of working memory and its reliance on dorsolateral prefrontal
      cortex (DLPFC) have been the focus of many studies in healthy subjects and in
      clinical populations. However, transfer of knowledge gained from cognitive
      science studies to clinical applications can be a challenging goal. This scarce
      cross-dissemination may be partially due to the use of 'tools' that are limited
      in their ability to generate meaningful information about impairments in clinical
      groups. To this end, this paper investigates the use of functional near-infrared
      spectroscopy (fNIRS), which offers unique opportunities for recording
      neuroactivation. Specifically, we examine measures of the DLPFC hemodynamic
      response during a working memory task in adults with traumatic brain injury (TBI)
      and healthy controls. Analysis of hemodynamic measures showed significant
      differences between the two groups, even without differences in behavioral
      performance. Additional subtle disparities were linked to levels of performance
      in TBI and healthy subjects. fNIRS hemodynamic measures may therefore provide
      novel information to existing theories and knowledge of the working memory
      construct. Future studies may further define these subtle differences captured by
      fNIRS to help identify which components affect inter-individual variations in
      performance and could play a contributing role in the choice and planning of
      neurorehabilitation interventions targeting working memory. 

PMID- 24085611
TI  - Orthodontic treatment for prominent lower front teeth (Class III malocclusion) in
      children.
AB  - BACKGROUND: Prominent lower front teeth (termed reverse bite; under bite; Class
      III malocclusion) may be due to a combination of the jaw or tooth positions or
      both. The upper jaw (maxilla) can be too far back or the lower jaw (mandible) too
      far forward, or both. Prominent lower front teeth can also occur if the upper
      front teeth (incisors) are tipped back or the lower front teeth are tipped
      forwards, or both. Various treatment approaches have been described to correct
      prominent lower front teeth in children and adolescents. OBJECTIVES: To assess
      the effects of orthodontic treatment for prominent lower front teeth in children
      and adolescents. SEARCH METHODS: We searched the following databases: Cochrane
      Oral Health Group's Trials Register (to 7 January 2013), the Cochrane Central
      Register of Controlled Trials (CENTRAL) (The Cochrane Library 2012, Issue 12),
      MEDLINE via OVID (1946 to 7 January 2013), and EMBASE via OVID (1980 to 7 January
      2013). SELECTION CRITERIA: Randomised controlled trials (RCTs) recruiting
      children or adolescents or both (aged 16 years or less) receiving any type of
      orthodontic treatment to correct prominent lower front teeth (Class III
      malocclusion). Orthodontic treatments were compared with control groups who
      received either no treatment, delayed treatment or a different active
      intervention. DATA COLLECTION AND ANALYSIS: Screening of references,
      identification of included and excluded studies, data extraction and assessment
      of the risk of bias of the included studies was performed independently and in
      duplicate by two review authors. The mean differences with 95% confidence
      intervals were calculated for continuous data. Meta-analysis was only undertaken
      when studies of similar comparisons reported comparable outcome measures. A fixed
      effect model was used. The I2 statistic was used as a measure of statistical
      heterogeneity. MAIN RESULTS: Seven RCTs with a total of 339 participants were
      included in this review. One study was assessed as at low risk of bias, three
      studies were at high risk of bias, and in the remaining three studies risk of
      bias was unclear. Four studies reported on the use of a facemask, two on the chin
      cup, one on the tandem traction bow appliance, and one on mandibular headgear.
      One study reported on both the chin cup and mandibular headgear appliances.One
      study (n = 73, low quality evidence), comparing a facemask to no treatment,
      reported a mean difference (MD) in overjet of 4.10 mm (95% confidence interval
      (CI) 3.04 to 5.16; P value < 0.0001) favouring the facemask treatment. Two
      studies comparing facemasks to untreated control did not report the outcome of
      overjet. Three studies (n = 155, low quality evidence) reported ANB (an angular
      measurement relating the positions of the top and bottom jaws) differences
      immediately after treatment with a facemask when compared to an untreated
      control. The pooled data showed a statistically significant MD in ANB in favour
      of the facemask of 3.93  degrees  (95% CI 3.46 to 4.39; P value < 0.0001). There
      was significant heterogeneity between these studies (I2 = 82%). This is likely to
      have been caused by the different populations studied and the different ages at
      the time of treatment.One study (n = 73, low quality evidence) reported outcomes
      of the use of the facemask compared to an untreated control at three years follow
      up. This study showed that improvements in overjet and ANB were still present
      three years post-treatment. In this study, adverse effects were reported but due
      to the low prevalence of temporomandibular (TMJ) signs and symptoms no analysis
      was undertaken.Two studies (n = 90, low quality evidence) compared the chin cup
      with an untreated control. Both studies found a statistically significant
      improvement in ANB, and one study also found an improvement in the Wits
      appraisal. Data from these two studies were not suitable for pooling.A single
      study of the tandem traction bow appliance compared to untreated control (n = 30,
      very low quality evidence) showed a statistically significant difference in both
      overjet and ANB favouring the intervention group.The remaining two studies did
      not report the primary outcome of this review. AUTHORS' CONCLUSIONS: There is
      some evidence that the use of a facemask to correct prominent lower front teeth
      in children is effective when compared to no treatment on a short-term basis.
      However, in view of the general poor quality of the included studies, these
      results should be viewed with caution. Further randomised controlled trials with
      long follow-up are required.

PMID- 24085610
TI  - Effects of cannabis and familial loading on subcortical brain volumes in first
      episode schizophrenia.
AB  - Schizophrenia is a severe neuropsychiatric disorder with familial loading as
      heritable risk factor and cannabis abuse as the most relevant environmental risk
      factor up to date. Cannabis abuse has been related to an earlier onset of the
      disease and persisting cannabis consumption is associated with reduced symptom
      improvement. However, the underlying morphological and biochemical brain
      alterations due to these risk factors as well as the effects of gene
      environmental interaction are still unclear. In this magnetic resonance imaging
      (MRI) study in 47 first-episode schizophrenia patients and 30 healthy control
      subjects, we investigated effects of previous cannabis abuse and increased
      familial risk on subcortical brain regions such as hippocampus, amygdala, caudate
      nucleus, putamen, thalamus and subsegments of the corpus callosum (CC). In a
      subsequent single-volume (1)H-magnetic resonance spectroscopy study, we
      investigated spectra in the left hippocampus and putamen to detect metabolic
      alterations. Compared to healthy controls, schizophrenia patients displayed
      decreased volumes of the left hippocampus, bilateral amygdala and caudate nucleus
      as well as an increased area of the midsagittal CC1 segment of the corpus
      callosum. Patients fulfilling the criteria for cannabis abuse at admission showed
      an increased area of the CC2 segment compared to those who did not fulfill the
      criteria. Patients with a family history of schizophrenia combined with previous
      cannabis abuse showed lower volumes of the bilateral caudate nucleus compared to
      all other patients, implicating an interaction between the genetic background and
      cannabis abuse as environmental factor. Patients with cannabis abuse also had
      higher ratios of N-acetyl aspartate/choline in the left putamen, suggesting a
      possible neuroprotective effect in this area. However, antipsychotic medication
      prior to MRI acquisition and gender effects may have influenced our results.
      Future longitudinal studies in first-episode patients with quantification of
      cannabis abuse and assessment of schizophrenia risk genes are warranted.

PMID- 24085612
TI  - Association of functional polymorphisms in the MxA gene with susceptibility to
      enterovirus 71 infection.
AB  - Myxovirus resistance A (MxA) is an antiviral protein induced by type I
      interferons alpha and beta (IFN-alpha and IFN-beta) that can inhibit virus
      replication. We examined whether the MxA polymorphisms were related to the risk
      and severity of enterovirus 71 (EV71) infection in Chinese populations. The MxA C
      123A and G-88T polymorphisms were genotyped in two independent case-control
      populations in China by polymerase chain reaction-based restriction fragment
      length polymorphism (PCR-RFLP) analysis. Multivariate logistic regression
      analysis was used to calculate adjusted odds ratios (ORs) and 95% confidence
      intervals (95% CIs). MxA messenger RNA was quantified by real-time quantitative
      PCR in peripheral blood mononuclear cells (PBMCs) from 45 healthy children and 19
      patients with EV71 infection. Significantly decreased susceptibility to EV71
      infection was observed for the -123A allele and -88T allele carriers, with ORs
      (95% CIs) estimated as 0.56 (0.39-0.81) and 0.64 (0.47-0.88), respectively, in
      the northern population. This association was confirmed in the southern
      population, with ORs (95% CIs) estimated as 0.58 (0.38-0.89) and 0.67(0.47-0.95),
      respectively. The A- 123T- 88 haplotype was also significantly associated with
      lower risk of EV71 infection in both the northern (OR = 0.62; 95% CI = 0.44-0.85)
      and the southern population (OR = 0.63; 95% CI = 0.43-0.92). Furthermore, we
      observed higher MxA messenger RNA levels in IFNbeta1a-stimulated PBMCs from the 
      123A or -88T allele carriers compared with that from nocarriers. Our findings
      suggest that polymorphisms in the MxA promoter may play a role in mediating the
      susceptibility to EV71 infection in Chinese population.

PMID- 24085613
TI  - Patterns of human oral yeast species distribution on Hainan Island in China.
AB  - Infections by yeast strains of the genus Candida are among the most prevalent
      fungal infections of humans. These yeasts are common residents of the oral mucosa
      and other body surfaces. Since most yeast infections are due to endogenous
      strains and that species of Candida differ in virulence properties and in
      intrinsic susceptibilities to antifungal drugs, understanding the human commensal
      yeast flora can help designing effective treatment and prevention strategies
      against yeast infections. Here, we report the patterns of yeast species
      distributions in the oral cavities of 1,799 people from Hainan Island in southern
      China. Based on sequence information at the fungal barcode locus ITS regions, 368
      of the 415 obtained oral yeast strains were identified as belonging to 26 yeast
      species, while the remaining 47 strains all showed significant sequence
      divergence to the currently described species. The four most common yeast species
      were C. albicans (42 %), C. tropicalis (20 %), C. glabrata (5.5 %), and C.
      parapsilosis (4.1 %) and 10 of the 26 yeast species were represented by only one
      strain each. Our analyses identified that the gender of hosts and ethnical
      background showed no contribution to oral yeast species distributions. However,
      the health status, place of birth, current residency, and the age of hosts all
      showed significant contributions to the distributions of the four dominant yeast
      species. We compared our results with those reported previously and discussed the
      potential mechanisms for the observed differences in oral yeast species
      distributions. 

PMID- 24085614
TI  - Fatal-mixed cutaneous zygomycosis-aspergillosis: a case report.
AB  - Mucorales and Aspergillus are molds responsible for infections in
      immunocompromised patients. In this report, we describe a case of a rare
      extensively mixed cutaneous infection caused by Lichtheimia ramosa, Aspergillus
      fumigatus and Aspergillus terreus in a neutropenic patient suffering from an
      acute leukemia. The fatal outcome of this patient can be attributed to its
      hematologic malignancy, the extensive nature of the lesions and the resistance of
      the strains to antifungals. 

PMID- 24085615
TI  - Madurella mycetomatis as an agent of brain abscess: case report and review of
      literature.
AB  - Fungal cerebral abscesses are rare and usually seen in immunocompromised
      individuals. We report a case and review published literature of Madurella
      mycetomatis as an agent of cerebral abscess. We found contiguous head and neck
      infections to be the principal cause of cerebral maduromycosis caused by M.
      mycetomatis. Early recognition of Madurella spp. as the causative agent is
      essential to avoid cerebral spread. 

PMID- 24085617
TI  - Threat of heavy metal contamination in eight mangrove plants from the Futian
      mangrove forest, China.
AB  - Mangrove plants play an important role in heavy metal maintenance in a mangrove
      ecosystem. To evaluate the characteristics of heavy metal contamination in the
      Futian mangrove forest, Shenzhen, China, eight heavy metals in mangrove sediments
      and plants were monitored, including essential elements such as Cu and Zn, and
      non-essential elements such as Cr, Ni, As, Cd, Pb and Hg. The results showed that
      the heavy metals exhibited the following scheme: Zn > As > Cu ~ Cr > Pb > Ni > Cd
      ~ Hg in sediment cores, among which Cd, As, Pb and Hg contents were nearly ten
      times higher than the background values. There was no significant difference in
      metal maintenance capability between native and exotic species. In mangrove
      plants' leaves and stems, concentrations of Cu, Zn and As were higher than other
      heavy metals. The low bioconcentration factors for most heavy metals, except for
      Cr, implied the limited ability of heavy metal accumulation by the plants.
      Mangrove plants seem to develop some degree of tolerance to Cr. The factor
      analysis implies that anthropogenic influences have altered metal mobility and
      bioavailability.

PMID- 24085616
TI  - The mechanisms linking adiposopathy to type 2 diabetes.
AB  - Obesity is defined as excessive accumulation of body fat in proportion to body
      size. When obesity occurs, the functions of adipose tissue may be deregulated,
      which is termed as adiposopathy. Adiposopathy is an independent risk factor for
      many diseases, including diabetes and cardiovascular diseases. In overweight or
      obese subjects with adiposopathy, hyperlipidemia exerts lipotoxicity in
      pancreatic islet and liver and induces pancreatic beta cell dysfunction and liver
      insulin resistance, which are the decisive factors causing type 2 diabetes.
      Moreover, adipokines have been shown to play important roles in the regulation of
      glucose homeostasis. When adiposopathy occurs, abnormal changes in the serum
      adipokine profile correlate with the development and progression of pancreatic
      beta cell dysfunction and insulin resistance in peripheral tissue. The current
      paper briefly discusses the latest findings regarding the effects of adiposopathy
      related lipotoxicity and cytokine toxicity on the development of type 2 diabetes.

PMID- 24085618
TI  - A systematic review of pharmacological pain management in multiple sclerosis.
AB  - BACKGROUND: Both chronic and acute pain have been cited as the most common
      symptoms amongst patients with multiple sclerosis (MS), with recent prevalence
      estimates as high as 83 %. The evidence for spasticity and trigeminal neuralgia
      pharmacological treatments in MS has been systematically reviewed, but no
      equivalent reviews have been published concerning MS pain unrelated to these two
      conditions. OBJECTIVE: Our objective was to systematically review pain management
      strategies for the reduction of non-spastic and non-trigeminal neuralgic pain in
      MS patients. DATA SOURCES: Experimental studies published after 1965 were chosen
      for review by searching electronic databases (e.g. PubMed, Cumulative Index to
      Nursing and Allied Health Literature, Science Citation Index Expanded, Conference
      Proceedings Citation Index-Science, and clinicaltrials.gov) and
      bibliographies/citations of previously published reviews. STUDY SELECTION:
      Studies were included if all participants were adults clinically diagnosed with
      MS, study sample was not restricted to participants with spasticity or trigeminal
      neuralgia, and participant-reported pain was a primary or secondary outcome
      measured with a validated tool. STUDY APPRAISAL AND SYNTHESIS METHODS: Records
      were screened and methodological qualities of included studies were assessed
      independently by two reviewers under the supervision of another reviewer using
      the principles recommended in the Cochrane Handbook for Systematic Review of
      Interventions and the levels of evidence espoused by the American Academy of
      Neurology. RESULTS: Fifteen studies met the inclusion and exclusion criteria for
      review; interventions included antidepressants, anticonvulsants,
      dextromethorphan/quinidine, cannabinoids, and opioids/opioid antagonists. The
      pooled effect size for anticonvulsants (4 studies, 78 participants) was -1.88 (95
      % CI: -3.13 to -0.64). The pooled effect size for cannabinoids (3 studies, 565
      participants) was 0.08 (95 % CI: -0.74 to 0.89). Overall, only four trials
      reported Class 1 evidence. For these trials, dizziness was the most commonly
      reported adverse event, followed by nausea and somnolence. LIMITATIONS: The
      relatively small number of trials in MS patients with chronic pain precludes
      specific recommendations for treatment strategies. The review did not reveal any
      studies of drug combinations. CONCLUSIONS: More trials with rigorous design and
      reporting are needed to determine effective treatments for specific pain types
      presenting in people living with MS.

PMID- 24085619
TI  - Long-term fructose feeding changes the expression of leptin receptors and
      autophagy genes in the adipose tissue and liver of male rats: a possible link to
      elevated triglycerides.
AB  - Long-term fructose consumption has been shown to evoke leptin resistance, to
      elevate triglyceride levels and to induce insulin resistance and hepatic
      steatosis. Autophagy has been suggested to function in processes such as lipid
      storage in adipose tissue and inflammation in liver. Autophagy and the leptin
      system have also been suggested to regulate each other. This study aimed to
      identify the changes caused by fetal undernourishment and postnatal fructose diet
      in the gene expression of leptin, its receptors (LEPR-a, LEPR-b, LEPR-c, LEPR-e
      and LEPR-f) and autophagy genes in the white adipose tissue (WAT) and liver of
      adult male rats in order to clarify the mechanism behind the metabolic
      alterations. The data clearly revealed that the long-term postnatal fructose diet
      decreased leptin levels (p < 0.001), LEPR (p < 0.001), especially LEPR-b (p =
      0.011) and LEPR-f (p = 0.005), as well as SOCS3 (p < 0.001), ACC (p = 0.006),
      ATG7 (p < 0.001), MAP1LC3beta (p < 0.001) and LAMP2 (p = 0.004) mRNA expression
      in WAT. Furthermore, LEPR (p < 0.001), especially LEPR-b (p = 0.001) and LEPR-f
      (p < 0.001), ACC (p = 0.010), ATG7 (p = 0.024), MAP1LC3beta (p = 0.003) and LAMP2
      (p < 0.001) mRNA expression in the liver was increased in fructose-fed rats. In
      addition, the LEPR expression in liver and MAP1LC3beta expression in WAT together
      explained 55.7 % of the variation in the plasma triglyceride levels of the rats
      (R adj. (2)  = 0.557, p < 0.001). These results, together with increased p62
      levels in WAT (p < 0.001), could indicate decreased adipose tissue lipid storing
      capacity as well as alterations in liver metabolism which may represent a
      plausible mechanism through which fructose consumption could disturb lipid
      metabolism and result in elevated triglyceride levels. 

PMID- 24085620
TI  - Bisphenol A exposure at an environmentally relevant dose induces meiotic
      abnormalities in adult male rats.
AB  - Whether environmental exposure to bisphenol A (BPA) may induce reproductive
      disorders is still controversial but certain studies have reported that BPA may
      cause meiotic abnormalities in C. elegans and female mice. However, little is
      known about the effect of BPA on meiosis in adult males. To determine whether BPA
      exposure at an environmentally relevant dose could induce meiotic abnormalities
      in adult male rats, we exposed 9-week-old male Wistar rats to BPA by gavage at 20
      MUg/kg body weight (bw)/day for 60 consecutive days. We found that BPA
      significantly increased the proportion of stage VII seminiferous epithelium and
      decreased the proportion of stage VIII. Consequently, spermiation was inhibited
      and spermatogenesis was disrupted. Further investigation revealed that BPA
      exposure delayed meiosis initiation in the early meiotic stage and induced the
      accumulation of chromosomal abnormalities and meiotic DNA double-strand breaks
      (DSBs) in the late meiotic stage. The latter event subsequently activated the
      phosphatidylinositol 3-kinase-related protein kinase (ATM). Our results suggest
      that long-term exposure to BPA may lead to continuous meiotic abnormalities and
      ultimately put mammalian reproductive health at risk. 

PMID- 24085622
TI  - A data-based model to locate mass movements triggered by seismic events in
      Sichuan, China.
AB  - Earthquakes affect the entire world and have catastrophic consequences. On May
      12, 2008, an earthquake of magnitude 7.9 on the Richter scale occurred in the
      Wenchuan area of Sichuan province in China. This event, together with subsequent
      aftershocks, caused many avalanches, landslides, debris flows, collapses, and
      quake lakes and induced numerous unstable slopes. This work proposes a
      methodology that uses a data mining approach and geographic information systems
      to predict these mass movements based on their association with the main and
      aftershock epicenters, geologic faults, riverbeds, and topography. A dataset
      comprising 3,883 mass movements is analyzed, and some models to predict the
      location of these mass movements are developed. These predictive models could be
      used by the Chinese authorities as an important tool for identifying risk areas
      and rescuing survivors during similar events in the future. 

PMID- 24085621
TI  - Occurrences and fate of selected human antibiotics in influents and effluents of
      sewage treatment plant and effluent-receiving river Yamuna in Delhi (India).
AB  - Antibiotics consumption has increased worldwide, and their residues are
      frequently reported in aquatic environments. It is believed that antibiotics
      reach aquatic water bodies through sewage. Medicine consumed for healthcare
      practices are often released into sewage, and after sewage treatment plant, it
      reaches the receiving water bodies of lakes or rivers. In the present study, we
      determined the fate of some commonly used antibiotics in a sewage treatment plant
      (STP) located in Delhi and the environmental concentration of these antibiotics
      in the Yamuna River, which receives the sewage and industrial effluent of Delhi.
      There are many reports on antibiotics occurrences in STP and river water
      worldwide, but monitoring data from the Indian subcontinent is sparse. Samples
      were taken from a STP and from six sampling sites on the Yamuna River. Several
      antibiotics were tested for using offline solid-phase extraction followed by high
      performance liquid chromatography equipped with photodiode array analysis.
      Recoveries varied from 25.5-108.8 %. Ampicillin had the maximum concentration in
      wastewater influents (104.2 +/- 98.11 MUg l(-1)) and effluents (12.68 +/- 8.38
      MUg l(-1)). The fluoroquinolones and cephalosporins had the lower concentrations.
      Treatment efficiencies varied between 55 and 99 %. Significant amounts of
      antibiotics were discharged in effluents and were detected in the receiving water
      body. The concentration of antibiotics in the Yamuna River varied from not
      detected to 13.75 MUg l(-1) (ampicillin) for the compounds investigated. 

PMID- 24085623
TI  - Sub-hourly changes in biogeochemical properties in surface waters of Zuari
      estuary, Goa.
AB  - Processes in natural waters are highly variable in time and space. Although
      changes are expected in short-time scales, how short one could get to measure
      reliably is subjective to sampling strategies and methodologies. Here, we show
      that sub-hourly changes in surface waters dissolved oxygen, nutrients, and
      pigments are measurable and significant in an estuarine system. Tidal circulation
      has been found to strongly influence the observed changes and has implications to
      material fluxes in and out of estuaries. 

PMID- 24085626
TI  - Rosmarinic acid inhibits chemical hypoxia-induced cytotoxicity in primary
      cultured rat hepatocytes.
AB  - We examine the effect of rosmarinic acid (RA) in chemical hypoxia-induced injury
      in rat hepatocytes. Cell viability was significantly decreased by cobalt chloride
      (CoCl2), a well-known hypoxia mimetic agent in a time- and dose- dependent
      manner. RA pretreatment before exposure to CoCl2 significantly attenuated the
      CoCl2-induced decrease of cell viability. Additionally, pretreatment with RA
      potentiated the decrease of Bcl-2 expression and attenuated the increase of
      Caspase-3 expression by CoCl2. CoCl2 treatment resulted in an increase of
      intracellular ROS generation, which is inhibited by RA or N-acetyl-cysteine (NAC,
      a ROS scavenger), and p38MAPK phosphorylation, which is also blocked by RA or
      NAC. CoCl2-induced increase of Bax/Bcl-2 ratio and Caspase-3 expression was
      attenuated by RA, NAC and SB203580 (p38MAPK inhibitor). CoCl2-induced decrease of
      cell viability was also attenuated by RA, NAC and SB203580 pretreatment.
      Additionally, RA inhibited CoCl2-induced COX-2 expression and prostaglandin E2
      (PGE2) secretion. Similar to the effect of RA, both NAC and NS-398 (COX-2
      inhibitor) blocked CoCl2-induced COX-2 expression and PGE2 secretion. NS-398
      attenuated not only CoCl2-induced increase of Bax/Bcl-2 ratio and Caspase-3
      expression, but decrease of cell viability. Taken together, RA protects primary
      cultured rat hepatocytes against CoCl2-induced cell injury through inhibition of
      ROS-activated p38MAPK and COX-2/PGE2 pathway. 

PMID- 24085627
TI  - Comparative evaluation of gastroulcerogenic potential of nitrogen isoforms of
      salicyl alcohol and aspirin in rats: biochemical and histological study.
AB  - The aim of the current study was to explore in vivo any relative
      gastroulcerogenic prospective propensity of newly synthesized nitrogen containing
      derivatives of salicyl alcohol; compound (I) [1-(2-hydroxybenzyl)piperidinium
      chloride], compound (II) [4-carbamoyl-1-(2-hydroxybenzyl)piperidinium chloride]
      and aspirin in albino rats. The experimental groups received the following oral
      treatments daily for 6 days: group I saline control; group II, standard (aspirin)
      treatment group [150 mg/kg of body weight]; group III, test (compound I)
      treatment group [100, 150 mg/kg]; group IV, test (compound II) treatment group
      [100, 150 mg/kg]. The results showed that in the case of the aspirin treated
      group and compound (I) [150 mg/kg], there was a significant increase in gastric
      volume, free acidity, total acidity, ulcer score and a decrease in gastric pH.
      Furthermore, histopathological examination of gastric mucosa of these treated
      groups revealed detectable morphological changes. Utilizing the same protocol,
      synthetic compound (I) [100 mg/kg] and (II) [100, 150 mg/kg] exhibited no
      statistically significant ulcerogenic or cytotoxic properties. A cyclooxygenase
      (COX) selectivity test indicated the preferential inhibition of COX-I and COX-II
      enzymes by compounds (I) and (II). This study therefore indicates that these
      synthetic compounds may possess reduced ulcerogenic potential and could be a
      functional substitute to aspirin.

PMID- 24085625
TI  - Cost effectiveness of treatments for stroke prevention in atrial fibrillation:
      focus on the novel oral anticoagulants.
AB  - For more than 5 decades, the only available treatment for the prevention of
      atrial fibrillation (AF)-related stroke were the vitamin K antagonists. Recently,
      novel oral anticoagulants (NOAC) have been approved for the prevention of AF
      related stroke. In the present article, the cost effectiveness of AF-related
      stroke-prevention strategies is reviewed. The emphasis on NOACs aims to provide
      an overview of their impact on health economics based on the published cost
      effectiveness analyses. The available evidence suggests that the balance from the
      efficacy and safety point of view makes the treatment with the NOACs a cost
      effective alternative to warfarin. Thus, the NOACs offer efficacy, safety and
      convenience, as well as cost effectiveness, for stroke prevention in AF. 

PMID- 24085624
TI  - Social epidemiology of diabetes and associated conditions.
AB  - Research focusing on the social determinants of diabetes has focused on
      individual-level factors such as health behaviors, socioeconomic status, and
      depression. Fewer studies that incorporate a broader consideration of the
      multiple contexts or organizational levels (eg, family, health care setting,
      neighborhood) within which individuals are embedded exist in the mainstream
      diabetes literature. Such an approach would enhance our understanding of this
      complex disease, and thus, future avenues of research should consider the
      following: (1) a life-course approach, which examines the influence of early life
      exposures on the development of diabetes; (2) aiming to understand the biological
      mechanisms of social determinants of diabetes; and (3) implementing interventions
      on multiple levels. Integrating this multilevel and life-course approach will
      require transdisciplinary science that brings together highly specialized
      expertise from multiple disciplines. Broadening the study of social determinants
      is a necessary step toward improving the prevention and treatment of type 2
      diabetes. 

PMID- 24085628
TI  - Metabonomics study on the hot syndrome of traditional Chinese medicine by rapid
      resolution liquid chromatography combined with quadrupole time-of-flight tandem
      mass spectrometry.
AB  - The hot syndrome refers to any feverish conditions during a pathological
      development, a sub-health phenomenon, and is a potential risk for human health.
      The metabonomics study on the hot syndrome may provide insight into understanding
      of its pathology and play a role in the prevention and treatment of its related
      diseases. In this paper, the rats were dosed with the hot syndrome prescription,
      ginseng and water. The corresponding urine samples were identified by rapid
      resolution liquid chromatography combined with quadrupole time-of-flight tandem
      mass spectrometry. More than 1,000 metabolic compounds from different urine
      samples could be further differentiated by principal component analysis. As a
      result, the rat body temperature and weight were recognized as the hot syndrome
      related factors. Some specific metabolites have been discovered as a pattern of
      the potential biomarkers for the hot syndrome. The results showed that ginseng
      cannot cause the hot syndrome in a reasonable dose, but the hot syndrome
      prescription can. It is suggested that ginseng cannot be used only as a tradition
      Chinese medicine but also as a nutrient. The work showed metabonomics method is a
      valuable tool in studying mechanism of the hot syndrome. 

PMID- 24085629
TI  - Echinacea purpurea root extract enhances the adipocyte differentiation of 3T3-L1
      cells.
AB  - Echinacea purpurea has been shown to have anti-diabetic activities; for example,
      it activates peroxisome proliferator-activated receptor gamma (PPARgamma) and
      increases insulin-stimulated glucose uptake. Adipogenesis has been used to study
      the insulin signaling pathway and to screen anti-diabetic compounds. The present
      study was conducted to investigate the effects of an ethanol extract of E.
      purpurea (EEEP) and its constituents on the insulin-induced adipocyte
      differentiation of 3T3-L1 preadipocytes. When adipocyte differentiation was
      induced with insulin plus 3-isobutyl-1-methylxanthine and dexamethasone, the
      accumulation of lipid droplets and the cellular triglyceride content were
      significantly increased by EEEP. The expressions of PPARgamma and C/EBPalpha in
      adipocytes treated with EEEP were gradually increased as compared with control
      cells. Fat accumulation and triglyceride content of adipocytes treated with
      dodeca-2(E),4(E)-dienoic acid isobutylamide were significantly increased as
      compared with control cells. The expressions of PPARgamma and C/EBPalpha in
      adipocytes treated with dodeca-2(E),4(E)-dienoic acid isobutylamide were
      significantly higher than in control cells. These results suggest EEEP promotes
      the adipogenesis that is partially induced by insulin and that dodeca-2(E),4(E)
      dienoic acid isobutylamide appears to be responsible for EEEP-enhanced adipocyte
      differentiation.

PMID- 24085630
TI  - Chemical constituents and their acetyl cholinesterase inhibitory and antioxidant
      activities from leaves of Acanthopanax henryi: potential complementary source
      against Alzheimer's disease.
AB  - The aim of this study was to investigate chemical constituents of the leaves of
      Acanthopanax henryi, and their antioxidant, acetyl cholinesterase inhibitory
      activities. Caffeoyl quinic acid derivates and flavonoids were obtained from A.
      henry, through column chromatography technologies, and the content of major
      constituents was determined by the HPLC-UV method. Anti-oxidant activity of the
      isolated metabolites was evaluated by free radical scavenging (DPPH, ABTS
      radicals) and superoxide anion scavenging. The results showed that di-caffeoyl
      quinic acid derivates had stronger antioxidant activity than positive controls
      (ascorbic acid, trolox and allopurinol). Acetyl cholinesterase inhibitory
      activity was estimated on the constituents, among which, quercetin, 4-caffeoyl
      quinic acid and 4,5-caffeoyl quinic acid were found to have strong acetyl
      cholinesterase inhibitory activity with IC50 values ranging from 62.6 to 121.9
      MUM. The present study showed that some of the tested constituents from the
      leaves of A. henryi exhibit strong antioxidant and acetyl cholinesterase
      inhibitory effects. This suggest that the leaves of A. henryi can be used as a
      new natural complementary source of acetyl cholinesterase inhibitors and anti
      oxidant agents, thus being a promising potential complementary source against
      Alzheimer's disease.

PMID- 24085631
TI  - Physical training for asthma.
AB  - BACKGROUND: People with asthma may show less tolerance to exercise due to
      worsening asthma symptoms during exercise or other reasons such as deconditioning
      as a consequence of inactivity. Some may restrict activities as per medical
      advice or family influence and this might result in reduced physical fitness.
      Physical training programs aim to improve physical fitness, neuromuscular
      coordination and self confidence. Subjectively, many people with asthma report
      that they are symptomatically better when fit, but results from trials have
      varied and have been difficult to compare because of different designs and
      training protocols. Also, as exercise can induce asthma, the safety of exercise
      programmes needs to be considered. OBJECTIVES: To gain a better understanding of
      the effect of physical training on the respiratory and general health of people
      with asthma, from randomised trials. SEARCH METHODS: We searched the Cochrane
      Airways Group Specialised Register of trials up to January 2013. SELECTION
      CRITERIA: We included randomised trials of people over eight years of age with
      asthma who were randomised to undertake physical training or not. Physical
      training had to be undertaken for at least 20 minutes, two times a week, over a
      minimum period of four weeks. DATA COLLECTION AND ANALYSIS: Two review authors
      independently assessed eligibility for inclusion and undertook risk of bias
      assessment for the included studies. MAIN RESULTS: Twenty-one studies (772
      participants) were included in this review with two additional 2012 studies
      identified as 'awaiting classification'. Physical training was well tolerated
      with no adverse effects reported. None of the studies mentioned worsening of
      asthma symptoms following physical training. Physical training showed marked
      improvement in cardiopulmonary fitness as measured by a statistically and
      clinically significant increase in maximum oxygen uptake (mean difference (MD)
      4.92 mL/kg/min; 95% confidence interval (CI) 3.98 to 5.87; P < 0.00001; 8 studies
      on 267 participants); however, no statistically significant effects were observed
      for forced expiratory volume in 1 second (FEV1), forced vital capacity (FVC),
      minute ventilation at maximal exercise (VEmax) or peak expiratory flow rate
      (PEFR). Meta-analysis of four studies detected a statistically significant
      increase in maximum heart rate, and following a sensitivity analysis and removal
      of two studies significance was maintained (MD 3.67 bpm; 95% CI 0.90 to 3.44; P =
      0.01). Although there were insufficient data to pool results due to diverse
      reporting tools, there was some evidence to suggest that physical training may
      have positive effects on health-related quality of life, with four of five
      studies producing a statistically and clinically significant benefit. AUTHORS'
      CONCLUSIONS: This review demonstrated that physical training showed significant
      improvement in maximum oxygen uptake, though no effects were observed in other
      measures of pulmonary function. Physical training was well tolerated among people
      with asthma in the included studies and, as such, people with stable asthma
      should be encouraged to participate in regular exercise training, without fear of
      symptom exacerbation. More research is needed to understand the mechanisms by
      which physical activity impacts asthma management.

PMID- 24085632
TI  - Spermicide used alone for contraception.
AB  - BACKGROUND: Spermicides have been used as contraceptives for thousands of years.
      Despite this long use, only recently have studies examined the comparative
      efficacy and acceptability of these vaginal medications. Spermicides contain an
      active ingredient (most commonly nonoxynol-9) and a formulation used to disperse
      the product, such as foam or vaginal suppository. OBJECTIVES: This review
      examined all known randomized controlled trials of a spermicide used alone for
      contraception. SEARCH METHODS: In August 2013, we searched the following
      computerized databases for randomized controlled trials of spermicides for
      contraception: CENTRAL, MEDLINE, POPLINE, LILACS, EMBASE, ClinicalTrials.gov, and
      ICTRP. For the initial review, we examined the reference lists of trials found as
      well as those of review articles and textbook chapters. SELECTION CRITERIA: We
      included any trial of a commercial product used alone for contraception. Each
      included trial must have provided sufficient information to determine pregnancy
      rates. DATA COLLECTION AND ANALYSIS: Two authors independently extracted
      information from the trials identified. We did not conduct a meta-analysis, since
      most trials had large losses to follow up. We entered the data into tables and
      presented the results descriptively. MAIN RESULTS: We located reports from 14
      trials for the initial review, but have not identified any new trials since then.
      In the largest trial to date, the gel (Advantage S) containing the lowest dose of
      nonoxynol-9 (52.5 mg) was significantly less effective in preventing pregnancy
      than were gels with higher doses of the same agent (100 mg and 150 mg).
      Probabilities of pregnancy by six months were 22% for the 52.5 mg gel, 16% for
      the 100 mg dose, and 14% for the 150 mg dose. In the same trial, the three
      different vehicles with 100 mg of nonoxynol-9 had similar efficacy.
      Interpretation of these figures is limited, since 39% of participants
      discontinued the method or were lost from the trial. Few important differences in
      efficacy emerged in other trials. AUTHORS' CONCLUSIONS: The probability of
      pregnancy varied widely in reported trials. A gel containing nonoxynol-9 52.5 mg
      was inferior to two other products tested in the largest trial. Aside from this
      finding, personal characteristics and behavior of users may be more important
      than characteristics of the spermicide products in determining the probability of
      pregnancy. Gel was liked more than the film or vaginal suppository in the largest
      trial. Spermicide trials have the dual challenges of difficult recruitment and
      high discontinuation rates; the latter threatens trial validity.

PMID- 24085633
TI  - Analgesia for forceps delivery.
AB  - BACKGROUND: A forceps delivery may be indicated when a fetus fails to progress to
      delivery, or when delivery needs to be expedited in the second stage of labour.
      Effective analgesia is required to ensure that the woman is comfortable
      throughout the delivery, to allow the obstetrician to safely perform the
      procedure. It is currently unclear what the most effective and safe agent or
      method is to provide pain relief during forceps delivery. OBJECTIVES: To assess
      the effectiveness and safety of different analgesic agents and methods available
      for forceps delivery for women and their babies. SEARCH METHODS: We searched the
      Cochrane Pregnancy and Childbirth Group's Trials Register (31 July 2013),
      reviewed published guidelines and searched the reference lists of review
      articles. SELECTION CRITERIA: Randomised controlled trials comparing an analgesic
      agent or method used for forceps delivery with placebo/no treatment or an
      alternative agent or method. DATA COLLECTION AND ANALYSIS: Two review authors
      independently assessed study eligibility, extracted data and assessed the risk of
      bias of included studies. MAIN RESULTS: We included four trials involving 388
      women that were judged to be at an unclear to high risk of bias overall. A
      variety of different agents for providing analgesia were assessed in the trials,
      and a number of different methods to measure pain relief were used, and thus
      results could not be combined in meta-analysis. Three trials compared diazepam
      with an alternative agent (ketamine; vinydan-ether; "other" anaesthesic agent)
      for the provision of general anaesthesia, and one trial compared spinal analgesia
      to pudendal nerve block (in both groups lignocaine was administered).With regard
      to the primary outcomes, women receiving diazepam for forceps delivery in one
      small trial were more likely to judge their pain relief as effective compared
      with women receiving vinydan-ether (risk ratio (RR) 1.13; 95% confidence interval
      (CI) 1.02 to 1.25; 101 women). In a further small trial, no significant
      difference was seen in the number of women judging their pain relief as effective
      when diazepam was compared with ketamine (RR 1.42; 95% CI 0.98 to 2.07; 26
      women). In the trial that compared spinal analgesia to pudendal nerve block,
      women receiving spinal analgesia were significantly more likely to regard their
      analgesia as adequate (RR 3.36; 95% CI 2.46 to 4.60; 183 women) and were less
      likely to report severe pain during forceps delivery (RR 0.02; 95% CI 0.00 to
      0.27; 183 women). No trials reported on the review's other two primary outcomes
      of serious maternal adverse effects or complications, and neonatal mortality or
      serious morbidity.In terms of secondary outcomes, women receiving diazepam
      compared with vinydan-ether, were significantly less likely to experience
      vomiting (RR 0.04; 95% CI 0.00 to 0.62; 101 women). No significant differences
      were seen for the few neonatal outcomes that were reported across any of the
      comparisons (including Agpar score of less than seven at five minutes and
      acidosis as defined by cord blood arterial pH less than 7.2). AUTHORS'
      CONCLUSIONS: There is insufficient evidence to support any particular analgesic
      agent or method as most effective in providing pain relief for forceps delivery.
      Neonatal outcomes have largely not been evaluated.

PMID- 24085634
TI  - Flexible sigmoidoscopy versus faecal occult blood testing for colorectal cancer
      screening in asymptomatic individuals.
AB  - BACKGROUND: Colorectal cancer is the third most frequent cancer in the world. As
      the sojourn time for this cancer is several years and a good prognosis is
      associated with early stage diagnosis, screening has been implemented in a number
      of countries. Both screening with faecal occult blood test and flexible
      sigmoidoscopy have been shown to reduce mortality from colorectal cancer in
      randomised controlled trials. The comparative effectiveness of these tests on
      colorectal cancer mortality has, however, never been evaluated, and controversies
      exist over which test to choose. OBJECTIVES: To compare the effectiveness of
      screening for colorectal cancer with flexible sigmoidoscopy to faecal occult
      blood testing. SEARCH METHODS: We searched MEDLINE and EMBASE (November 16,
      2012), the Cochrane Central Register of Controlled Trials (CENTRAL) (2012, Issue
      11) and reference lists for eligible studies. SELECTION CRITERIA: Randomised
      controlled trials comparing screening with flexible sigmoidoscopy or faecal
      occult blood testing to each other or to no screening. Only studies reporting
      mortality from colorectal cancer were included. Faecal occult blood testing had
      to be repeated (annually or biennially). DATA COLLECTION AND ANALYSIS: Data
      retrieval and assessment of risk of bias were performed independently by two
      review authors. Standard meta-analyses using a random-effects model were
      conducted for flexible sigmoidoscopy and faecal occult blood testing (FOBT)
      separately and we calculated relative risks with 95% confidence intervals (CI).
      We used a Bayesian approach (a contrast-based network meta-analysis method) for
      indirect analyses and presented the results as posterior median relative risk
      with 95% credibility intervals. We assessed the quality of evidence using GRADE.
      MAIN RESULTS: We identified nine studies comprising 338,467 individuals
      randomised to screening and 405,919 individuals to the control groups. Five
      studies compared flexible sigmoidoscopy to no screening and four studies compared
      repetitive guaiac-based FOBT (annually and biennially) to no screening. We did
      not consider that study risk of bias reduced our confidence in our results. We
      did not identify any studies comparing the two screening methods directly. When
      compared with no screening, colorectal cancer mortality was lower with flexible
      sigmoidoscopy (relative risk 0.72; 95% CI 0.65 to 0.79, high quality evidence)
      and FOBT (relative risk 0.86; 95% CI 0.80 to 0.92, high quality evidence). In the
      analyses based on indirect comparison of the two screening methods, the relative
      risk of dying from colorectal cancer was 0.85 (95% credibility interval 0.72 to
      1.01, low quality evidence) for flexible sigmoidoscopy screening compared to
      FOBT. No complications occurred after the FOBT test itself, but 0.03% of
      participants suffered a major complication after follow-up. Among more than
      60,000 flexible sigmoidoscopy screening procedures and almost 6000 work-up
      colonoscopies, a major complication was recorded in 0.08% of participants.
      Adverse event data should be interpreted with caution as the reporting of adverse
      effects was incomplete. AUTHORS' CONCLUSIONS: There is high quality evidence that
      both flexible sigmoidoscopy and faecal occult blood testing reduce colorectal
      cancer mortality when applied as screening tools. There is low quality indirect
      evidence that screening with either approach reduces colorectal cancer deaths
      more than the other. Major complications associated with screening require
      validation from studies with more complete reporting of harms

PMID- 24085635
TI  - Ultrastructure of the anterior intestinal epithelia of the orange-spotted grouper
      Epinephelus coioides larvae under different feeding regimes.
AB  - Enterocytes of the anterior to midsection of the intestine in grouper Epinephelus
      coioides larvae were compared among different treatments: unfed to the point-of
      no-return (PNR), fed natural food only, and co-fed natural food and artificial
      diet. On day 3, the nutritional condition of unfed grouper larvae regressed with
      its reduced enterocyte heights which were further degraded on day 4, the PNR,
      when all the enterocytes were in advanced stages of apoptosis. The apoptosis
      appeared to be internally directed via the mitochondria. Among day 3 fed larvae,
      enterocyte heights of those fed artificial diet did not differ from those fed
      natural food only. Dietary phospholipid deficiency was indicated in larvae co-fed
      artificial diet on day 3 with an unusually large chylomicron opening into the
      inter-enterocyte space, and on days 6 and 33 by intestinal steatosis. On day 19,
      scant to absent lipid droplets in enterocytes of larvae disclosed heightened
      nutritional requirement preparatory to metamorphosis. As observed in unfed day 3
      and premetamorphic day 19 E. coioides, larvae undergoing critical periods and
      starvation during development employ apoptosis to dispose of degenerated
      enterocytes that are phagocytosed by adjacent healthy enterocytes without causing
      inflammatory distress. Upon metamorphosis, grouper larval gut develops better
      immunity fitness with eosinophilic granule cells observed in the intestinal
      epithelia of day 33 larvae. Future studies on grouper larval nutrition may
      consider the appropriate dietary phospholipid levels and larval competence to
      biosynthesize highly unsaturated fatty acid from linoleic acid vis-a-vis the use
      of plant ingredients in artificial diet formulations. In vivo challenge tests may
      validate appropriate dietary nutrient supplementation and lead to better feed
      formulation, matching the varying energetic demands and digestive capacities of
      developing E. coioides larvae. 

PMID- 24085637
TI  - Variations in nitrogen-15 natural abundance of plant and soil systems in four
      remote tropical rainforests, southern China.
AB  - The foliar stable N isotope ratio (delta(15)N) can provide integrated information
      on ecosystem N cycling. Here we present the delta(15)N of plant and soil in four
      remote typical tropical rainforests (one primary and three secondary) of southern
      China. We aimed to examine if (1) foliar delta(15)N in the study forests is
      negative, as observed in other tropical and subtropical sites in eastern Asia;
      (2) variation in delta(15)N among different species is smaller compared to that
      in many N-limited temperate and boreal ecosystems; and (3) the primary forest is
      more N rich than the younger secondary forests and therefore is more (15)N
      enriched. Our results show that foliar delta(15)N ranged from -5.1 to 1.30/00 for
      39 collected plant species with different growth strategies and mycorrhizal
      types, and that for 35 species it was negative. Soil NO3 (-) had low delta(15)N (
      11.4 to -3.20/00) and plant NO3 (-) uptake could not explain the negative foliar
      delta(15)N values (NH4 (+) was dominant in the soil inorganic-N fraction). We
      suggest that negative values might be caused by isotope fractionation during soil
      NH4 (+) uptake and mycorrhizal N transfer, and by direct uptake of atmospheric
      NH3/NH4 (+). The variation in foliar delta(15)N among species (by about 60/00)
      was smaller than in many N-limited ecosystems, which is typically about or over
      100/00. The primary forest had a larger N capital in plants than the secondary
      forests. Foliar delta(15)N and the enrichment factor (foliar delta(15)N minus
      soil delta(15)N) were higher in the primary forest than in the secondary forests,
      albeit differences were small, while there was no consistent pattern in soil
      delta(15)N between primary and secondary forests.

PMID- 24085636
TI  - Incorporating common biomarkers into the clinical management of heart failure.
AB  - Heart failure is a prevalent and costly disease, and its management with
      polypharmacy is complex. Commonly available biomarkers primarily help to 1)
      establish or refute the diagnosis of heart failure; 2) help to determine the
      disease severity; and 3) identify adverse consequences of treatment. Although
      several of them are commonly ordered (such as electrolytes, renal and liver
      function), their use is primarily based on broad clinical experience rather than
      established evidence. The availability of cardiac-specific natriuretic peptide
      testing has provided an evidence-based breakthrough in our abilities to establish
      the diagnosis and severity of heart failure, yet the appropriate boundaries to
      guide management are still in refinement. 

PMID- 24085638
TI  - Neighborhoods have little effect on fungal attack or insect predation of
      developing seeds in a grassland biodiversity experiment.
AB  - Numerous observational studies have documented conspecific negative density
      dependence that is consistent with the Janzen-Connell Hypothesis (JCH) of
      diversity maintenance. However, there have been few experimental tests of a
      central prediction of the JCH: that removing host-specific enemies should lead to
      greater increases in per capita recruitment in areas of higher host density or
      lower relative phylogenetic diversity. Using spatially randomized plots of high
      and low host biomass in a temperate grassland biodiversity experiment, we treated
      developing seedheads of six prairie perennials to factorial applications of
      fungicide and insecticide. We measured predispersal seed production, seed
      viability, and seedling biomass. Results were highly species-specific and
      idiosyncratic. Effects of insect seed predators and fungal pathogens on
      predispersal responses varied with neither conspecific biomass nor phylogenetic
      diversity, suggesting that-at least at the predispersal stage and for the insect
      and fungal seed predators we were able to exclude-the JCH is not sufficient to
      contribute to negative conspecific density-dependence for these dominant prairie
      species. 

PMID- 24085639
TI  - Myrmecochores can target high-quality disperser ants: variation in elaiosome
      traits and ant preferences for myrmecochorous Euphorbiaceae in Brazilian
      Caatinga.
AB  - Recent evidence suggests that the traditional view of myrmecochory as a highly
      diffuse interaction between diaspores and a wide range of ant species attracted
      to their elaiosomes may not be correct. The effectiveness of dispersal varies
      markedly among ant species, and combined with differential attractiveness of
      diaspores due to elaiosome size and composition, this raises the potential for
      myrmecochorous plants to target ant species that offer the highest quality
      dispersal services. We ask the question: Do particular physical and chemical
      traits of elaiosomes result in disproportionate removal of Euphorbiaceae
      diaspores by high-quality disperser ants in Caatinga vegetation of north-eastern
      Brazil? We offered seeds of five euphorb species that varied in morphological and
      chemical traits of elaiosomes to seed-dispersing ants. High-quality seed
      disperser ants (species of Dinoponera, Ectatomma and Camponotus) were identified
      as those that rapidly collected and transported diaspores to their nests, often
      over substantial distances, whereas low-quality disperser ants (primarily species
      of Pheidole and Solenopsis) typically fed on elaiosomes in situ, and only ever
      transported diaspores very short distances. Low-quality disperser ants were
      equally attracted to the elaiosomes of all study species. However, high-quality
      dispersers showed a strong preference for diaspores with the highest elaiosome
      mass (and especially proportional mass). As far as we are aware, this is the
      first study to identify a mechanism of diaspore selection by high-quality ant
      dispersers based on elaiosome traits under field conditions. Our findings suggest
      that myrmecochorous plants can preferentially target high-quality seed-disperser
      ants through the evolution of particular elaiosome traits. 

PMID- 24085640
TI  - A simple scoring system for risk-stratifying rectal cancer patients prior to
      radical resection.
AB  - BACKGROUND: Various predictors of perioperative risk for patients with rectal
      cancer undergoing radical resection have been well described, but no simple
      scoring system for surgeons to estimate this risk currently exists. The objective
      of this study was to develop a system for more accurate preoperative evaluations
      of competing risks and more informed shared decision-making with patients
      diagnosed with rectal cancer. METHODS: The National Surgical Quality Improvement
      Program-Participant Use Data File for 2005-2011 was used to retrospectively
      identify patients undergoing radical resection for rectal cancer. A forward
      stepwise multivariable logistic regression model was used to create a dynamic
      scoring system to preoperatively estimate a patient's risk of major
      complications. RESULTS: A total of 6,847 patients met study inclusion criteria.
      Thirteen risk factors were identified, and using these predictive variables, a
      scoring system was derived to stratify major complication risk after radical
      resection. CONCLUSIONS: The risk of a major complication after radical resection
      for rectal cancer is dependent on multiple preoperative variables. This study
      provides surgeons with a simple but effective tool for estimating major
      complication risk in rectal cancer patients prior to radical resection. This risk
      stratification score serves as a patient-centered resource for discussing
      perioperative risks and assisting with the shared decision-making of operative
      planning.

PMID- 24085641
TI  - Interventions for replacing missing teeth: hyperbaric oxygen therapy for
      irradiated patients who require dental implants.
AB  - BACKGROUND: Dental implants offer one way to replace missing teeth. Patients who
      have undergone radiotherapy and those who have also undergone surgery for cancer
      in the head and neck region may particularly benefit from reconstruction with
      implants. Hyperbaric oxygen therapy (HBO) has been advocated to improve the
      success of implant treatment in patients who have undergone radiotherapy but this
      remains a controversial issue. OBJECTIVES: To compare the success, morbidity,
      patient satisfaction and cost effectiveness of dental implant treatment carried
      out with and without HBO in irradiated patients. SEARCH METHODS: The following
      electronic databases were searched: the Cochrane Oral Health Group's Trials
      Register (to 17 June 2013), the Cochrane Central Register of Controlled Trials
      (CENTRAL) (The Cochrane Library 2013, Issue 5), MEDLINE via OVID (1946 to 17 June
      2013) and EMBASE via OVID (1980 to 17 June 2013). No restrictions were placed on
      the language or date of publication when searching the electronic databases. We
      checked the bibliographies of relevant clinical trials and review articles for
      studies outside the searched journals. We wrote to authors of the identified
      randomised controlled trials (RCTs) and to more than 55 oral implant
      manufacturers; we used personal contacts and we made a request on an internet
      discussion group in an attempt to identify unpublished or ongoing RCTs. SELECTION
      CRITERIA: Randomised controlled trials (RCTs) of HBO therapy for irradiated
      patients requiring dental implants. DATA COLLECTION AND ANALYSIS: Screening of
      eligible studies, assessment of the methodological quality of the trials and data
      extraction were conducted in duplicate and independently by two review authors.
      Results were analysed using random-effects models to determine mean differences
      for continuous outcomes and risk ratios for dichotomous outcomes, with 95%
      confidence intervals. MAIN RESULTS: Only one RCT, providing very low quality
      evidence, was identified and included. Thirteen patients received HBO therapy
      while another 13 did not. Two to six implants were placed in people with fully
      edentulous mandibles to be rehabilitated with bar-retained overdentures. One year
      after implant loading, four patients had died from each group. One patient,
      treated with HBO, developed an osteoradionecrosis and lost all implants so the
      prosthesis could not be provided. Five patients in the HBO group had at least one
      implant failure versus two in the control group. There were no statistically
      significant differences for prosthesis and implant failures, postoperative
      complications and patient satisfaction between the two groups. AUTHORS'
      CONCLUSIONS: Despite the limited amount of clinical research available, it
      appears that HBO therapy in irradiated patients requiring dental implants may not
      offer any appreciable clinical benefits. There is a definite need for more RCTs
      to ascertain the effectiveness of HBO in irradiated patients requiring dental
      implants. These trials ought to be of a high quality and reported as recommended
      by the CONSORT statement (www.consort-statement.org/). Each clinical centre may
      have limited numbers of patients and it is likely that trials will need to be
      multicentred.

PMID- 24085642
TI  - Paracervical local anaesthesia for cervical dilatation and uterine intervention.
AB  - BACKGROUND: Cervical dilatation and uterine intervention can be performed under
      sedation, local or general anaesthesia for obstetrics and gynaecological
      conditions. Many gynaecologists use paracervical local anaesthesia but its
      effectiveness is unclear. This review was originally published in 2009 and was
      updated in 2013. OBJECTIVES: The objectives of this review were to determine the
      effectiveness and safety of paracervical local anaesthesia for cervical
      dilatation and uterine intervention, versus no treatment, placebo, other methods
      of regional anaesthesia, sedation and systemic analgesia, and general
      anaesthesia. SEARCH METHODS: We reran our search to August 2013. We searched the
      Cochrane Central Register of Controlled Trials (CENTRAL) (The Cochrane Library
      2013, Issue 8), MEDLINE (1966 to August 2013), EMBASE (1980 to August 2013), and
      reference lists of articles. The original search was performed in January 2006.
      SELECTION CRITERIA: We included randomized or controlled clinical studies
      involving women who underwent cervical dilatation and uterine intervention for
      obstetrics and gynaecological conditions. We included studies which compared
      paracervical anaesthesia with no treatment, placebo, other methods of regional
      anaesthesia, systemic sedation and analgesia, or general anaesthesia. DATA
      COLLECTION AND ANALYSIS: Two authors independently evaluated the studies,
      extracted data, and checked and entered data into Review Manager. MAIN RESULTS:
      This updated review includes nine new studies, in total 26 studies with 28
      comparisons and involving 2790 participants. No study of local paracervical
      versus general anaesthesia met our criteria. Ten studies compared local
      anaesthetic versus placebo. Paracervical local anaesthetic (PLA) reduced pain on
      cervical dilatation with a standardized mean difference (SMD) of 0.37 (95% CI
      0.17 to 0.58) and a relative risk (RR) of severe pain of 0.16 (95% CI 0.06 to
      0.74). PLA also reduced abdominal pain during, but not after, uterine
      intervention (SMD 0.74, 95% CI 0.28 to 1.19); there was no evidence of any effect
      on postoperative back or shoulder pain. Comparisons against no treatment did not
      demonstrate any effect of PLA. Five studies compared paracervical block with
      uterosacral block, intracervical block, or intrauterine topical anaesthesia. Two
      of these studies showed no significant difference in pain during the procedure.
      Compared to intrauterine instillation, PLA slightly reduced severe pain (from 8.3
      to 7.6 on a 10-point scale), which may be negligible. Six studies compared PLA
      with sedation. There were no statistically significant differences in pain during
      or after the procedure, postoperative analgesia requirement, adverse effects,
      patient satisfaction, and the operator's perception of analgesia. We performed
      risk of bias assessment using six domains and found that more than half of the
      included studies had low risk of bias. AUTHORS' CONCLUSIONS: We found that no
      technique provided reliable pain control in the 26 included studies. Some studies
      reported that women experienced severe pain (mean scores of 7 to 9 out of 10)
      during uterine intervention, irrespective of the analgesic technique used. We
      concluded that the available evidence fails to show whether paracervical block is
      inferior, equivalent, or superior to alternative analgesic techniques in terms of
      efficacy and safety for women undergoing cervical dilatation and uterine
      interventions. We suggest that woman are likely to consider the rates and
      severity of pain during uterine interventions when performed awake to be
      unacceptable in the absence of neuraxial blockade, which are unaltered by
      paracervical block.

PMID- 24085643
TI  - Supratentorial gross-totally resected non-anaplastic ependymoma: population based
      patterns of care and outcomes analysis.
AB  - Observation following gross-total resection (GTR) for non-anaplastic
      supratentorial ependymomas is often advocated based on small, retrospective
      series. The purpose of this study is to perform a population-based analysis to
      examine outcomes for this rare cohort of low-risk patients. A retrospective
      analysis was conducted utilizing the Surveillance, Epidemiology and End Results
      Program of the United States National Cancer Institute. We identified patients
      with supratentorial non-anaplastic ependymoma who underwent GTR alone or GTR
      followed by radiation. We identified 92 patients who met these criteria. The
      median age was 17.5 years (range 1-83) with the majority female (58 %) and white
      (75 %). Radiotherapy (RT) was delivered in half of patients. The 5-/10-year
      Kaplan-Meier estimated overall survival (OS) and cause-specific survival (CSS)
      for the overall cohort was 83.2/71.4 and 84.1/78.0 %, respectively. There was no
      evidence of decreased CSS (HR 0.52 [0.18-1.51]; p = 0.23) or OS (HR 0.63 [0.25
      1.59]; p = 0.33) with the omission of RT on univariate analysis. Age >=18 years
      correlated with worse OS (HR 4.01 [1.45-11.11]; p = 0.008) and CSS (HR 2.86 [0.99
      8.31]; p = 0.05). RT did not impact outcome for this low-risk cohort of patients.
      Older age correlates with poor prognosis.

PMID- 24085644
TI  - Natural killer cells in intracranial neoplasms: presence and therapeutic efficacy
      against brain tumours.
AB  - Natural killer (NK) cells are lymphocytes that play an important role in anti
      tumour immunity. Their potential against brain cancer has been demonstrated in
      vitro and in vivo, both as a direct anti-tumour agent and in experimental
      therapies stimulating endogenous NK cell cytotoxicity. However, the clinical
      translation of these promising results requires detailed knowledge about the
      immune status of brain tumour patients, with focus on the NK cell population. In
      this report, we provide an overview of the studies investigating NK cell
      infiltration into the tumour, emphasizing the need of revision of the
      methodologies and further research in this field. We also discuss the potential
      of using autologous or allogeneic NK cells as effector cells in cellular therapy
      against brain cancer and developing immunotherapies stimulating endogenous NK
      cell-mediated anti-tumour response, such as blocking inhibitory killer
      immunoglobulin-like receptors. Combination of NK cell adoptive transfer with
      targeted therapies, such as anti-EGFR therapeutic antibody (CetuximAb) could also
      be a potent strategy. 

PMID- 24085645
TI  - Protective effect of p-cymene on lipopolysaccharide-induced acute lung injury in
      mice.
AB  - In the previous study, the anti-inflammatory effect of p-cymene had been found.
      In this study, we investigated anti-inflammatory effects of p-cymene on acute
      lung injury using lipopolysaccharide (LPS)-induced acute lung injury (ALI) mouse
      model. The cell counting in the bronchoalveolar lavage fluid (BALF) was measured.
      The animal lung edema degree was evaluated by wet/dry weight (W/D) ratio. The
      superoxidase dismutase (SOD) activity and myeloperoxidase (MPO) activity was
      assayed by SOD and MPO kits, respectively. The levels of inflammatory mediators
      including tumor necrosis factor alpha (TNF-alpha), IL-1beta, and IL-6 were
      assayed by enzyme-linked immunosorbent assay method. The pathological changes of
      the lung tissues were observed by hematoxylin and eosin staining. The
      inflammatory signal pathway-related protein levels of NF-kappaB were measured
      using Western blotting. The data showed that treatment with the p-cymene markedly
      attenuated inflammatory cell numbers in the BALF, decreased NF-kappaB protein
      level in the lungs, improved SOD activity, and inhibited MPO activity.
      Histological studies demonstrated that p-cymene substantially inhibited LPS
      induced neutrophils in the lung tissue compared with the model group. The results
      indicated that p-cymene had a protective effect on LPS-induced ALI in mice. 

PMID- 24085646
TI  - Cognitive deficits in Friedreich ataxia correlate with micro-structural changes
      in dentatorubral tract.
AB  - Atrophy of the dentate nucleus is one of the major neuropathological changes in
      Friedreich ataxia (FRDA). Neuroimaging studies demonstrated white matter (WM)
      degeneration in FRDA. In this study, we used advanced tractography techniques to
      quantitatively measure WM changes in the dentato-thalamic and dentato-rubral
      tracts, and correlated these changes with cognitive profiles of FRDA. We also
      analysed diffusivity changes of the thalamo-cortical tract to assess whether
      neurological degeneration of WM extends beyond the primary site of involvement in
      FRDA. Twelve genetically proven individuals with FRDA and 14 controls were
      recruited. Sixty directions diffusion tensor images were acquired. The WM bundles
      from the dentate nucleus were estimated using a constrained spherical
      deconvolution method and the diffusivity characteristics measured. The Simon task
      was used to assess cognitive profile of FRDA. The dentato-rubral, dentato
      thalamic and thalamo-cortical tracts manifested significantly lower fractional
      anisotropy, higher mean diffusivity and increased radial diffusivity in FRDA
      compared with controls. There was no difference in axial diffusivity between the
      two groups. The mean and radial diffusivity of the dentato-rubral tract was
      positively correlated with choice reaction time, congruent reaction time,
      incongruent reaction time and Simon effect reaction time and negatively with the
      larger GAA repeat. Significant changes in diffusivity characteristics were
      observed in the dentato-thalamic and thalamo-cortical tracts, suggesting
      extensive WM degeneration and affected WM structures in FRDA. Correlation of WM
      changes in the dentato-rubral tract with the cognitive assessment suggested that
      this tract is an important contributor to cognitive disturbances in FRDA. 

PMID- 24085647
TI  - Metabolic evidence for cerebral neurodegeneration in spinocerebellar ataxia type
      1.
AB  - Autosomal-dominant spinocerebellar ataxia type 1 (SCA1) is an adult-onset
      progressive disorder with well-characterized neurodegeneration in the cerebellum
      and brainstem. The objective of this study is to evaluate neurochemical changes
      associated with neurodegeneration in cerebral tissue in SCA1 patients compared to
      age- and gender-matched healthy controls. Nine patients with genetically proven
      SCA1 and nine gender- and age-matched healthy controls were prospectively
      recruited from the ataxia clinic and received clinical examination. A 1.5 T
      single-voxel brain proton MR spectroscopy was performed for total N-acetyl
      aspartate (tNAA) in cerebellum, parietofrontal lobe white matter, sensory cortex,
      and visual cortex. In the patients, tNAA was severely decreased in the cerebellar
      voxel; however, in the voxels positioned in sensory cortex, parietofrontal lobe
      white matter and visual cortex tNAA was reduced in comparison to controls. In
      addition to the profoundly affected cerebellum, we also found evidence for
      cerebral neurodegeneration in parietal lobe white matter, sensory cortex, and
      visual cortex in SCA1 patients illustrating a multisystem neurodegenerative
      character of the disease. 

PMID- 24085648
TI  - Repairing ditched amalgam restorations is less time and tooth structure-consuming
      than replacement.
AB  - AIM: To evaluate the dental structure loss associated with procedures of
      replacement or maintenance for ditched amalgam restorations in primary molars and
      the time required to perform each treatment. METHODS: Ditched amalgam
      restorations (n = 40) were submitted to four different strategies: polishing
      group-polishing and finishing of restorations; amalgam group-replacement of
      ditched amalgam restorations with new amalgam restorations; resin group
      replacement of amalgam restorations with resin composite restorations; flowable
      resin group-filling the ditch with a flowable resin composite. The teeth were
      analysed with a stereomicroscope and the areas pre- and post-treatment were
      determined by image analysis software to evaluate structural loss. The time
      required to perform each treatment was recorded in seconds. STATISTICS: Student's
      t test was used to compare areas pre- and post-treatments. ANOVA and Student
      Newman-Keuls tests (p < 0.05) were used to compare differences among groups and
      the time to perform each procedure. RESULTS: Dental structure loss was observed
      in resin and amalgam groups. Replacing the restorations with amalgam took more
      time, while polishing and applying flowable resin composite consumed less than
      half of the time compared with amalgam and resin groups. CONCLUSION: Maintenance
      of ditched amalgam restorations by polishing and sealing preserves dental
      structure and involves less time compared with that for replacement of
      restorations.

PMID- 24085650
TI  - Optimal patient education for cancer pain: a systematic review and theory-based
      meta-analysis.
AB  - PURPOSE: Previous systematic reviews have found patient education to be
      moderately efficacious in decreasing the intensity of cancer pain, but variation
      in results warrants analysis aimed at identifying which strategies are optimal.
      METHODS: A systematic review and meta-analysis was undertaken using a theory
      based approach to classifying and comparing educational interventions for cancer
      pain. The reference lists of previous reviews and MEDLINE, PsycINFO, and CENTRAL
      were searched in May 2012. Studies had to be published in a peer-reviewed English
      language journal and compare the effect on cancer pain intensity of education
      with usual care. Meta-analyses used standardized effect sizes (ES) and a random
      effects model. Subgroup analyses compared intervention components categorized
      using the Michie et al. (Implement Sci 6:42, 2011) capability, opportunity, and
      motivation behavior (COM-B) model. RESULTS: Fifteen randomized controlled trials
      met the criteria. As expected, meta-analysis identified a small-moderate ES
      favoring education versus usual care (ES, 0.27 [-0.47, -0.07]; P = 0.007) with
      substantial heterogeneity (I2 = 71 %). Subgroup analyses based on the taxonomy
      found that interventions using "enablement" were efficacious (ES, 0.35 [-0.63, 
      0.08]; P = 0.01), whereas those lacking this component were not (ES, 0.18 [-0.46,
      0.10]; P = 0.20). However, the subgroup effect was nonsignificant (P = 0.39), and
      heterogeneity was not reduced. Factoring in the variable of individualized versus
      non-individualized influenced neither efficacy nor heterogeneity. CONCLUSIONS:
      The current meta-analysis follows a trend in using theory to understand the
      mechanisms of complex interventions. We suggest that future efforts focus on
      interventions that target patient self-efficacy. Authors are encouraged to report
      comprehensive details of interventions and methods to inform synthesis,
      replication, and refinement.

PMID- 24085649
TI  - Common dental features and craniofacial development of three siblings with Ter
      Haar syndrome.
AB  - BACKGROUND: Ter Haar syndrome is a rare genetic syndrome with <30 cases reported
      worldwide. There is nothing within the published literature regarding the dental
      development and dental features of these patients. CASE REPORT: This case series
      examines three patients with Ter Haar syndrome and tracks their dental
      development and identifies common dental and skeletal features. FOLLOW-UP: All
      three patients received dental treatment and regular follow-up at Great Ormond
      Street Hospital Dental Department. CONCLUSION: These patients have many common
      dental and craniofacial features which poses the question as to whether these
      features are due to Ter Haar syndrome.

PMID- 24085651
TI  - Osteoporosis and osteoarthritis, rheumatoid arthritis and spondylarthropathies.
AB  - Osteoporosis (OP) commonly occurs in the setting of inflammatory arthritis,
      whereas there is an inverse relationship with osteoarthritis (OA). We review the
      recent updates in epidemiology and pathophysiology of OP relating to several
      arthridities. In ankylosing spondylitis, lateral lumbar spine dual x-ray
      absorptiometry is better at detecting osteoporosis compared with the AP view and
      patients receiving treatment with anti- tumor necrosis factor medications had
      lower levels of bone turnover markers. With regard to rheumatoid arthritis,
      anticitrullinated peptide positivity without clinical arthritis as well as higher
      levels of interleukin-6 is associated with decreased bone mineral density and
      polymorphisms in the vitamin D receptor in RA patients may predispose to OP. With
      regard to OA, results from the Global Longitudinal Study of Osteoporosis in Women
      study and several radiological studies suggest that differences in the
      distribution of bone mass at the femoral neck may account for the inverse
      relationship of OA and OP, and several studies suggest that OA and OP have
      opposing cytokine and bone metabolism marker profiles. 

PMID- 24085652
TI  - Commentary: measuring quality of care in osteoporosis.
AB  - We know improving the quality of care in osteoporosis is an important goal. We
      have made some strides toward measuring quality of osteoporosis care, focusing on
      process measures regarding care that is provided. Unfortunately, improving care
      as measured by these process measures does not always yield improved outcomes. We
      need to hold health care providers and health care systems responsible not only
      for health care production but for production of health and well-being. However,
      there is a multiplicity of factors that will need to be considered to make this
      next step. 

PMID- 24085653
TI  - A 10-year retrospective cohort study on the risk factors for peritoneal dialysis
      related peritonitis: a single-center study at Tokai University Hospital.
AB  - BACKGROUND: Common outcomes of peritoneal dialysis (PD)-related peritonitis
      include catheter removal and transition to hemodialysis (HD). According to recent
      data, the incidence of PD-related peritonitis in Japan is not low, and
      peritonitis is the most common cause of withdrawal from PD. Against this
      backdrop, the purpose of this study is to determine the incidence of PD-related
      peritonitis at the Outpatient Nephrology Clinic of Tokai University Hospital
      (hereafter "the Clinic") and to examine causative bacteria and the risk factors
      related to the development of peritonitis. METHODS: We investigated all PD
      related peritonitis episodes of 192 PD patients who visited the Clinic during the
      period from April 1, 2001 to March 31, 2011 and established the incidence of PD
      related peritonitis, along with culture-negative peritonitis rates. Regarding the
      risk factors that are associated with the development of peritonitis, we examined
      patient backgrounds, whether an automated peritoneal dialysis (APD) device was
      used, and which type of connection system was employed. RESULTS: The incidence of
      peritonitis was one episode per 64.5 patient-months, and the culture-negative
      peritonitis rate was 16.4 %. Of the cultured bacterial isolates 71.3 % were Gram
      positive cocci, including 25.0 % of coagulase-negative staphylococci, 13.2 % of
      methicillin-susceptible Staphylococcus aureus (MSSA), and 6.6 % of methicillin
      resistant Staphylococcus aureus (MRSA). Gram-negative rods were 19.1 %. Risk
      factors associated with the development of peritonitis included age at the start
      of PD [odds ratio 1.042, 95 % confidence interval (CI) 1.016-1.069, p value =
      0.001], diabetes mellitus nephropathy (DMN) (odds ratio 22.003, 95 % CI 2.101
      230.452, p value = 0.010), and the use of a sterile tubing welder device (STWD)
      (odds ratio 2.399, 95 % CI 1.043-5.521, p value = 0.040). CONCLUSIONS: Regarding
      the situation of peritonitis at a single center during the 10-year period of this
      study, risk factors associated with the development of peritonitis included age
      at the start of PD, DMN, and the use of an STWD.

PMID- 24085654
TI  - Arthroscopic repair of large and massive rotator cuff tears using the biceps
      incorporating technique: mid-term clinical and anatomical results.
AB  - INTRODUCTION: The purpose of this study was to determine the anatomical and
      clinical outcomes of a biceps-incorporating rotator cuff repair without detaching
      the biceps origin from the glenoid in a large or massive rotator cuff tear, in
      which the biceps tendon could be incorporated into the cuff defect and help to
      provide tendon healing and prevent upward migration of the humeral head.
      MATERIALS AND METHODS: Thirty-five consecutive patients with a mean age of 62
      years (41-81 years) had primary arthroscopic repair of their large or massive
      rotator cuff in which biceps tendon incorporated into the cuff defect without
      detaching the biceps tendon from the glenoid was performed. Functional outcome
      was determined by the visual analog scale (VAS) for pain during motions, simple
      shoulder test (SST), the University of California, Los Angeles (UCLA) score, and
      the American Shoulder and Elbow Surgeons scores (ASES) (mean follow-up, 24
      months). The continuity of rotator cuff mechanism was evaluated using the
      magnetic resonance imaging (MRI) among all the patients after 2 years. RESULTS:
      At the final follow-up, mean VAS scores increased significantly from 7.1 to 2.0
      points, ASES scores from 35 to 83, UCLA scores from 14 to 30, and SST scores from
      4 to 9, respectively (p < 0.05). Moreover, the range of motion was significantly
      increased except the external rotation from preoperative 27 degrees  to
      postoperative 33 degrees  (p = 0.183). MRI evaluation showed that 22 of 35
      patients (63%) had heeled tendons and 7 patients (20%) had partial re-tear. Of 35
      patients, 6 (17%) had a complete re-tear. Only 3 of these 6 patients were not
      satisfied with the result. CONCLUSIONS: Using this simple biceps-incorporating
      rotator cuff repair technique, we achieved good clinical and moderate anatomical
      results, and prevent superior migration of the humeral head in a large or massive
      rotator cuff tear. LEVEL OF EVIDENCE: Level IV retrospective review.

PMID- 24085655
TI  - Long PHILOS plate fixation in a series of humeral fractures.
AB  - AIM: The purpose of the article is to highlight a specific fracture pattern
      encountered by us in the osteoporotic upper humerus. We present our results of
      management of such metadiaphyseal fractures of the upper humerus with less
      invasive plating. The additional steps taken to improve final outcome and the
      reasoning behind each are discussed. PATIENTS AND METHODS: In our department, a
      total of 13 fractures (in 12 patients) were managed for a metadiaphyseal fracture
      of the upper humerus between 2010 and 2013. There were 2 males and 10 females.
      The average age in the cohort was 74.3 (52-95) years. In 9 fractures, the
      fracture line was extending above the surgical neck. All patients were managed
      with a locking compression plate (long PHILOS or LCP) using two approach windows
      (proximal deltopectoral and a distal anterior or lateral). Patients were
      evaluated for clinical outcome using the Quick DASH score and assessed for
      radiological union, complications or re-operations retrospectively. RESULTS: The
      mean follow-up was 14.3 months (4-36). All fractures were united, and there was
      no evidence of avascular necrosis or non-union. Two patients showed varus
      collapse of the anatomical head of which one patient needed change of screws at
      12 weeks from index surgery. In patients, when a distal lateral window was used,
      2 patients out of 4 had radial nerve palsy post-operatively. In the rest, when
      the plate was twisted by 45 degrees  to allow anterior placement using the
      brachialis split, none had radial nerve injury. CONCLUSION: The osteoporotic bone
      failing under a low-energy mechanism seemed to dictate this fracture pattern. The
      fracture is either a bending wedge or a long spiral with or without a large
      butterfly and often extends into the humeral head. The fractures are better
      managed surgically, a primary reduction allowing contact of fragments is
      essential, and using an anterior window distally with a 45 degrees  contoured
      plate will achieve good plate placement as well as decreases the risk of radial
      nerve injury considerably compared to total lateral plate positioning.

PMID- 24085656
TI  - Reliability and acceptability of measuring sniff nasal inspiratory pressure
      (SNIP) and peak inspiratory flow (PIF) to assess respiratory muscle strength in
      older adults: a preliminary study.
AB  - BACKGROUND: Sniff nasal inspiratory pressure (SNIP) and peak oral inspiratory
      flow (PIF) are portable, relatively new methods for indirect measurement of
      respiratory muscle strength. The reliability and acceptability of these measures
      were investigated in older adults. METHODS: The study included 21 self-reported
      healthy adults, aged 65-84 years (mean 73.5; SD 6.4 years). Participants were
      tested in a sitting position on two occasions, 1 week apart. The best of three
      attempts for PIF measured through the mouth, and five for each nostril for SNIP
      were recorded. Reliability was tested using intra-class correlation coefficient
      (ICC), standard error of measurement, minimal detectable change (MDC) and Bland
      and Altman analysis. Feedback on the measures in relation to ease of completion
      and preference was obtained using a semi-structured interview. RESULTS: Between
      day reliability of SNIP and PIF were ICC3,1 0.76 (95 % CI 0.49-0.9) and 0.92
      (0.81-0.97), respectively. Standard error of measurement for SNIP (11.94 cmH2O)
      and MDC (33.10 cmH2O) were at the least 61 % higher than for PIF. The
      participants reported difficulties in performing SNIP, rating it as being less
      easy and uncomfortable to perform than PIF, with a higher rate of missing data
      for SNIP due to participants' dislike of the test. CONCLUSIONS: The wide range of
      SNIP readings, lower ICC value and negative user feedback are suggestive of a
      less robust and unacceptable clinical measure. PIF showed excellent reliability
      and acceptability and is therefore recommended for assessing inspiratory muscle
      strength in older people without known obstructive lung disease.

PMID- 24085657
TI  - Enzyme replacement therapy with laronidase (Aldurazyme) for treating
      mucopolysaccharidosis type I.
AB  - BACKGROUND: Mucopolysaccharidosis type I can be classified as three clinical sub
      types; Hurler syndrome, Hurler-Scheie syndrome and Scheie syndrome, with the
      scale of severity being such that Hurler syndrome is the most severe and Scheie
      syndrome the least severe. It is a rare, autosomal recessive disorder caused by a
      deficiency of alpha-L-iduronidase. Deficiency of this enzyme results in the
      accumulation of glycosaminoglycans within the tissues. The clinical
      manifestations are facial dysmorphism, hepatosplenomegaly, upper airway
      obstruction, skeletal deformity and cardiomyopathy. If Hurler syndrome is left
      untreated, death ensues by adolescence. There are more attenuated variants termed
      Hurler-Scheie or Scheie syndrome, with those affected potentially not presenting
      until adulthood. Enzyme replacement therapy has been used for a number of years
      in the treatment of Hurler syndrome, although the current gold standard would be
      a haemopoietic stem cell transplant in those diagnosed by 2.5 years of age.
      OBJECTIVES: To evaluate the effectiveness and safety of treating
      mucopolysaccharidosis type I with laronidase enzyme replacement therapy as
      compared to placebo. SEARCH METHODS: We searched the Cochrane Cystic Fibrosis and
      Genetic Disorders Group's Inborn Errors of Metabolism Trials Register, MEDLINE
      via OVID and EMBASE.Date of most recent search: 08 February 2013. SELECTION
      CRITERIA: Randomised and quasi-randomised controlled trials of laronidase enzyme
      replacement therapy compared to placebo. DATA COLLECTION AND ANALYSIS: Two
      authors independently screened the identified trials. The authors then appraised
      and extracted data. MAIN RESULTS: One study of 45 patients met the inclusion
      criteria. This double-blind, placebo-controlled, randomised, multinational trial
      looked at laronidase at a dose of 0.58 mg/kg/week versus placebo in patients with
      mucopolysaccharidosis type I. All primary outcomes listed in this review were
      studied in this trial. The laronidase group achieved statistically significant
      improvements in per cent predicted forced vital capacity compared to placebo, MD
      5.60 (95% confidence intervals 1.24 to 9.96) and in the six-minute-walk test
      (mean improvement of 38.1 metres in the laronidase group; P = 0.66, when using a
      prospectively planned analysis of covariance). The levels of urinary
      glycoaminoglycans were also significantly reduced. In addition, there were
      improvements in hepatomegaly, sleep apnoea and hypopnoea. Laronidase antibodies
      were detected in nearly all patients in the treatment group with no apparent
      clinical effect and titres were reducing by the end of the study. Infusion
      related adverse reactions occurred in both groups but all were mild and none
      necessitated medical intervention or infusion cessation. AUTHORS' CONCLUSIONS:
      The current evidence demonstrates that laronidase is effective when compared to
      placebo in the treatment of mucopolysaccharidosis type I. The included trial was
      comprehensive and of good quality, although there were few participants. The
      trial included all of the key outcome measures we wished to look at. It
      demonstrated that laronidase is efficacious in relation to reducing biochemical
      parameters(reduced urine glycosaminoglycan excretion) and improved functional
      capacity as assessed by forced vital capacity and the six-minute walk test. In
      addition glycosaminoglycan storage was reduced as ascertained by a reduction in
      liver volume. Laronidase appeared to be safe and, while antibodies were
      generated, these titres were reducing by the end of the study. More studies are
      required to determine long-term effectiveness and safety and to assess the impact
      upon quality of life. Enzyme replacement therapy with laronidase can be used pre-
      and peri-haemopoietic stem cell transplant, which is now the gold standard
      treatment in those patients diagnosed under 2.5 years of age.

PMID- 24085660
TI  - Self-assembly and gelation properties of glycine/leucine Fmoc-dipeptides.
AB  - Self-assembly of aromatic peptide amphiphiles is known to be driven by a
      combination of pi-pi stacking of the aromatic moieties and hydrogen bonding
      between the peptide backbones, with possible stabilisation from the amino acid
      side chains. Phenylalanine-based Fmoc-dipeptides have previously been reported
      for their characteristic apparent pKa transitions, which were shown to coincide
      with significant structural and morphological changes that were peptide sequence
      dependent. Here, phenylalanine was replaced by leucine and the effect on the self
      assembling behaviour of Fmoc-dipeptides was measured using potentiometry,
      fluorescence and infrared spectroscopy, transmission electron microscopy, X-ray
      scattering and shear rheometry. This study provides additional cues towards the
      elucidation of the sequence-structure relationship in self-assembling aromatic
      peptide amphiphiles. 

PMID- 24085659
TI  - Drug-induced long QT syndrome in women.
AB  - Congenital long QT syndromes (LQTS) are inherited heart diseases that can present
      as palpitations, syncope (fainting), seizures, cardiac arrest, and sudden death.
      Acquired LQTS mostly occurs as a result of exposure to an environmental stressor
      that is responsible for the excessive prolongation of the QT interval. The most
      common environmental stressor is adverse drug reactions, which can lead to drug
      induced LQTS (di-LQTS). Female gender has been increasingly recognized as an
      independent risk factor for di-LQTS, which in females is influenced by other
      factors, including age, menstrual cycle, and hormone replacement therapy. The
      estrogen-mediated reduced repolarization reserve in women is believed to be
      responsible for their higher susceptibility to di-LQTS. More studies, especially
      randomized trials, should be carried out to confirm these findings, and elucidate
      the clinical impact of gender disparity in modifying the risk of di-LQTS in
      women, with the ultimate goal of promoting the clinical safety of medication. In
      this article, we review current knowledge about di-LQTS, specifically in women,
      and discuss methods for the prevention of di-LQTS in females. 

PMID- 24085658
TI  - Autophagy as a neuroprotective mechanism against 3-nitropropionic acid-induced
      murine astrocyte cell death.
AB  - Huntington's disease (HD) is a genetic neurodegenerative disorder that is
      characterized by severe striatal atrophy with extensive neuronal loss and
      gliosis. Although the molecular mechanism is not well understood, experimental
      studies use the irreversible mitochondrial inhibitor 3-nitropropionic acid (3-NP)
      to mimic the neuropathological features of HD. In this study, the role of
      autophagy as a neuroprotective mechanism against 3-NP-induced astrocyte
      cytotoxicity was evaluated. Autophagy is a catabolic process that is essential
      for the turnover of cytosolic proteins and organelles and is involved in the
      modulation of cell death and survival. We showed that 3-NP-induced apoptosis,
      which was accompanied by Bax and Beclin-1 upregulation, was dependent on acidic
      vesicular organelle (AVO) formation after a continuous exposure to 3-NP for 12 h.
      The upregulation of Bax and Beclin-1 as well as AVO formation were normalized 24
      h after 3-NP exposure.

PMID- 24085662
TI  - Move over nurses: there's a new professional on the block.

PMID- 24085661
TI  - Osteoporosis and orthopedic surgery: effect of bone health on total joint
      arthroplasty outcome.
AB  - Osteoporosis is a common condition. As the population ages, more patients with
      osteoporosis will require orthopedic procedures, including arthroplasty. Adverse
      outcomes are more likely for patients with osteoporosis requiring orthopedic
      procedures, for example those with intraoperative fractures, periprosthetic
      osteolysis with implant migration, and postoperative periprosthetic fractures.
      Cemented prosthetic hip replacements may be more successful among patients with
      poor bone quality. Femoral neck fracture is a concern during hip resurfacing
      among patients with osteoporosis. Vitamin D deficiency is common among patients
      undergoing joint arthroplasty and the ideal vitamin D level for joint
      arthroplasty has yet to be determined. Both bisphosphonates and teriparatide may
      aide successful osteointegration among patients undergoing noncemented joint
      arthroplasty. Focusing on bone health perioperatively should result in better
      outcomes for orthopedic procedures. 

PMID- 24085663
TI  - Expanding theoretical thinking.

PMID- 24085664
TI  - Living on the edge: a review of the literature.
AB  - A comprehensive review of the literature of the universal experience of living on
      the edge is discussed. Literature was reviewed from biology, criminology,
      ecology, economics, ethics, finance, fine arts, historical biography, medicine,
      nursing, philosophy, physiology, psychology, sociology, and theology. Three
      themes emerged with this literature review: living on the edge as a sacred place
      one travels to or where one lives, living on the edge as a choice in taking risks
      and surviving danger, and living on the edge as engaging with health experiences
      in which persons and nurses coparticipate. Living on the edge is a visionary
      quest into a new frontier that holds illimitable possibilities that transform the
      world. The literature is discussed according to theoretical and research
      findings. 

PMID- 24085665
TI  - Protecting the discipline: collaboration revisited.
AB  - Collaboration has become requisite for the funding of research by the federal
      government because of the complex nature of health problems facing the nation.
      This column will present ideas from the National Institute of Health, the
      Institute of Medicine, the National Institute of Nursing Research, and the
      American Association of Colleges of Nursing that confirm the need for
      collaboration. The terms multidisciplinary, interdisciplinary, and
      transdisciplinary research will be considered as they apply to successful nursing
      research in light of loosely coupled systems. Finally, suggestions for productive
      interdisciplinary research will be put forth for the reader's consideration. 

PMID- 24085666
TI  - Ethical issues surrounding interprofessional collaboration.
AB  - Global healthcare and health disciplines' education policy and position
      statements contain mandates for education that incorporates interprofessional
      collaboration. One of the popular educational technologies involves virtual
      simulation as tools for educating future generations of healthcare professionals.
      This article discusses potential ethical implications for interprofessional
      collaboration from a humanbecoming lens of understanding.

PMID- 24085667
TI  - The ambiguities of loyalty.
AB  - Loyalty is a complex notion. Recognizing moments of loyalty in nursing can
      encourage pride in the profession and thereby assist in elevating nursing as a
      profession. If nurses can appreciate the complexities involved in loyalty, this
      knowing might assist them in understanding personal struggles with loyalty when
      they arise and may also help in the understandings-misunderstandings that can
      occur when a breach of loyalty is felt. In this column, this complexity is
      discussed. Loyalty as a part of living quality is also highlighted in that
      loyalty is always choosing value priorities in co-creating living quality.
      Furthermore, the principles of humanbecoming are used as a guide to teaching
      learning as well as recognizing loyalty in the nursing profession.

PMID- 24085668
TI  - Humanbecoming: a seamless symphony of theory in practice.
AB  - All that I believe and every interaction I have is written in Dr. Ortiz's column.
      Humanbecoming is a paradigm, a way of living nursing and life. It is something I
      cherish. Read and savor this wonderful story. 

PMID- 24085669
TI  - Everything is different, nothing is changed.
AB  - Sciencing and living the art of humanbecoming are a commitment to a specific
      ontology housed in the humanbecoming paradigm. This article is a reflection on
      Parse's unique humanbecoming paradigm and its postulates: illimitability,
      paradox, freedom, and mystery. It is important to interpret these postulates in
      ways that are personally unique, as all persons live humanbecoming in the
      emerging now in the endless sea of nows. 

PMID- 24085670
TI  - Nursing leadership: interprofessional education and practice.
AB  - The column presents a scholarly dialogue about nursing's role in
      interprofessional education, practice, and collaboration. Susan Hassmiller, PhD,
      RN, FAAN, is the Robert Wood Johnson Foundation (RWJF) senior adviser for
      nursing. In this role, she shapes and leads the foundation's strategies to
      address nurse and nurse faculty shortages and ensures that RWJF's commitments in
      nursing have a broad and lasting national impact. In partnership with AARP,
      Hassmiller directs the foundation's Future of Nursing: Campaign for Action. This
      effort, active in 50 states plus the District of Columbia, strives to implement
      the recommendations of the Institute of Medicine's 2011 report, The Future of
      Nursing: Leading Change, Advancing Health, for which Hassmiller served as the
      study director. 

PMID- 24085671
TI  - A Roy model study of adapting to being HIV positive.
AB  - Roy's adaptation model outlines a generic process of adaptation useful to nurses
      in any situation where a patient is facing change. To advance nursing practice,
      nursing theories and frameworks must be constantly tested and developed through
      research. This article describes how the results of a qualitative grounded theory
      study have been used to test components of the Roy adaptation model. A framework
      for "negotiating uncertainty" was the result of a grounded theory study exploring
      adaptation to HIV. This framework has been compared to the Roy adaptation model,
      strengthening concepts such as focal and contextual stimuli, Roy's definition of
      adaptation and her description of adaptive modes, while suggesting areas for
      further development including the role of perception. The comparison described in
      this article demonstrates the usefulness of qualitative research in developing
      nursing models, specifically highlighting opportunities to continue refining
      Roy's work. 

PMID- 24085672
TI  - Contemporary women's adaptation to motherhood: the first 3 to 6 weeks postpartum.
AB  - A better understanding of the process of adaptation to motherhood should enhance
      nurses' ability to prepare women for the transition to motherhood and to provide
      care following childbirth. Knowledge about women's adaptation to motherhood was
      developed primarily from the 1960s to the 1990s. Cesarean birthing was a special
      focus of research throughout the late 1970s and the 1980s, followed by functional
      status, and more recently, depression and stress associated with birth and
      postpartum. Adaptation to motherhood in the context of the early 21st century has
      received limited attention in nursing research, creating an assumption that the
      process of adaptation is universal and context-free rather than evolving within
      the life and societal context of women across generations. Although becoming and
      being a mother has been described as a normative transition rather than a
      stressor by some, knowledge development about adaptation to motherhood also has
      been constrained by the limited use of a unified perspective of transition as a
      process of adaptation. Therefore, the purposes of this exploratory study were to
      describe contemporary women's physical, emotional, functional, and social
      adaptation to motherhood and to examine the relations of selected demographic and
      perinatal variables to adaptation to motherhood in the first 3 to 6 weeks of the
      postpartum. 

PMID- 24085673
TI  - A case study based on Watson's theory of human caring: being an infertile woman
      in Turkey.
AB  - Nursing theories and models form a framework for systematizing nursing practices.
      In Turkey, nurses are generally organized on the basis of the medical model,
      which makes the essence of nursing invisible. The authors here aim to explain how
      to maintain a theory-based care approach for nurses working with persons
      experiencing infertility. The interaction between an infertile woman and a nurse
      is shared within the framework of Watson's theory of human caring. Watson's
      theory has been found useful for the infertile group in practice. 

PMID- 24085674
TI  - The prevention and reduction of postpartum complications: Orem's model.
AB  - This study was conducted using Orem's self-care model to investigate its impact
      on the reduction and prevention of women's postpartum complications. One group of
      63 women was included in the study in which a pretest and posttest quasi
      experimental method was used. For analysis of the data, descriptive statistics,
      dependent groups t test, and McNemar test were applied, 24 different nursing
      diagnoses were made. Self-care agency pretest mean score was 97.13 +/- 17.20,
      posttest mean score was 114.44 +/- 13.72, and the difference was statistically
      significant (p < .001). The study found that the care given to women in the
      postpartum period using Orem's self-care model prevented postpartum complications
      and increased the self-care agency of postpartum women. 

PMID- 24085675
TI  - Global health nursing: toward a human science-based approach.

PMID- 24085676
TI  - Building the Nightingale Initiative for Global Health--NIGH: can we engage and
      empower the public voices of nurses worldwide?
AB  - The Nightingale Initiative for Global Health (NIGH) is a major grassroots-to
      global movement of "daring, caring and sharing" of nursing and others around the
      world inspired by the outstanding legacy of Florence Nightingale. The Nightingale
      Initiative envisions and emulates what Nightingale might have accomplished if she
      lived in the digital age and with international agencies such as the United
      Nations and World Health Organization. It challenges nurses everywhere to think
      and act both locally and globally, to raise their voices about the contribution
      of nursing, and to become authentic advocates, particularly in addressing the
      United Nations Millennium Development Goals. 

PMID- 24085677
TI  - Ways of knowing about leadership in nursing.

PMID- 24085678
TI  - The bear and the canyon: toward an understanding of personal leadership.
AB  - Using Carper's fundamental patterns of knowing in nursing as a framework, the
      author reflects upon and intertwines experiences as a nurse leader and
      experiences in nature that called for resilience and courage. 

PMID- 24085679
TI  - Thoughts about multidisciplinary, interdisciplinary, and transdisciplinary
      research.
AB  - This essay focuses on multidisciplinary, interdisciplinary, and transdisciplinary
      research. The definitions and objectives for these three types of multiple
      discipline research are given. Discussion centers on the gains and losses that
      may be experienced by individual nurses who engage in such research, as well as
      gains and losses for the discipline of nursing. 

PMID- 24085681
TI  - Nursing Science Quarterly Best Paper Award: 2012.

PMID- 24085682
TI  - Liver steatosis (LS) evaluated through chemical-shift magnetic resonance imaging
      liver enzymes in morbid obesity; effect of weight loss obtained with intragastric
      balloon gastric banding.
AB  - The aim of this study was to evaluate in morbid obesity clinical and metabolic
      effects related to weight loss on liver steatosis (LS), measured through chemical
      shift magnetic resonance imaging (MRI) and liver enzymes. Forty obese subjects (8
      M/32 W; BMI 42.8 +/- 7.12 kg/m(2), mean +/- SD) were evaluated for LS through
      ultrasound (US-LS), chemical-shift MRI (MRI-LS), liver enzymes [aspartate
      aminotransferase (AST), alanine aminotransferase (ALT), gamma-glutamyltransferase
      (GGT), alkaline phosphatase (ALP)], anthropometric parameters [weight, BMI, waist
      circumference (WC)], lipids, insulin, insulin resistance (HOMA-IR), glycated
      hemoglobin (HbA1c), oral glucose tolerance test, and body composition [fat mass
      (FM) and fat-free mass (FFM) at bio-impedance analysis (BIA)]. Anthropometric
      measures, MRI-LS, BIA, and biochemical parameters were reevaluated 6 months later
      in 18 subjects undergoing restrictive bariatric approach, i.e., intragastric
      balloon (BIB, n = 13) or gastric banding (LAGB, n = 5), and in 13 subjects
      receiving hypocaloric diet. At baseline, US-LS correlates only with MRI-LS, and
      the latter correlates with ALT, AST, and GGT. After 6 months, subjects undergoing
      BIB or LAGB had significant changes of BMI, weight, WC, ALT, AST, GGT, ALP,
      HbA1c, insulin, HOMA-IR, FM, FFM, and MRI-LS. Diet-treated obese subjects had no
      significant change of any parameter under study; change of BMI, fat mass, and fat
      free mass was significantly greater in LAGB/BIB subjects than in diet-treated
      subjects. Change of MRI-LS showed a significant correlation with changes in
      weight, BMI, WC, GGT, ALP, and basal MRI-LS. Significant weight loss after BIB or
      LAGB is associated with decrease in chemical-shift MRI-LS and with reduction in
      liver enzymes; chemical-shift MRI and liver enzymes allow monitoring of LS in
      follow-up studies. 

PMID- 24085683
TI  - Monocyte-macrophage polarization balance in pre-diabetic individuals.
AB  - Pre-diabetes is characterized by increased cardiovascular risk and chronic
      inflammation. The activation of monocyte-macrophages plays major roles in
      vascular biology. Herein, we aimed to analyze monocyte-macrophage polarization
      status in subjects with IFG and/or IGT compared with normal glucose tolerant
      (NGT) individuals. We enrolled 87 middle-aged individuals with low prevalence of
      cardiovascular disease. Based on OGTT, they were divided into 49 NGT and 38 pre
      diabetic (IFG and/or IGT). Using flow cytometry analysis of peripheral blood
      cells, we quantified traditional monocyte subsets based on CD14 and CD16
      expression as well as novel monocyte-macrophage pro-inflammatory CD68(+)CCR2(+)
      M1 and anti-inflammatory CX3CR1(+)CD163(+)/CD206(+) M2 phenotypes. The M1/M2
      ratio was taken to represent the polarization balance. There were no differences
      in traditional classical (CD14(++)CD16(-)), intermediate (CD14(++)CD16(+)) and
      nonclassical (CD14(+)CD16(+)) monocytes between groups. Rather, compared to NGT,
      pre-diabetic subjects showed a significant increase in pro-inflammatory M1 cells
      and percent expression of the oxLDL scavenger receptor CD68, without changes in
      anti-inflammatory M2 cells. M1 levels and CD68 expression were directly
      correlated with HbA1c. We show for the first time that otherwise healthy pre
      diabetic subjects have excess M1 inflammatory cells in peripheral blood, which
      may contribute to cardiovascular risk.

PMID- 24085684
TI  - Abstracts of the 2013 Annual Meeting of the American College of Rheumatology.
      October 25-30, 2013. San Diego, California, USA.

PMID- 24085685
TI  - AZA-deoxycytidine stimulates proopiomelanocortin gene expression and ACTH
      secretion in human pituitary ACTH-secreting tumors.
AB  - PURPOSE: It is well known that methylation plays an important role in regulating
      tissue expression of proopiomelanocortin (POMC) and recent studies have shown
      that demethylation can occur also in vitro in neuroendocrine tumors. Aim of the
      present study was to evaluate whether inhibition of methylation modulates POMC
      expression and ACTH secretion by human corticotrope tumors. METHODS: Twenty two
      ACTH-secreting pituitary tumors were incubated with 5-AZA-2'-deoxycytidine (AZA),
      an inhibitor of DNA-methyltransferases, with or without 10 nM corticotropin
      releasing hormone (CRH). Both dose response (100 nM-10 MUM AZA) and time course
      (4-96 h) experiments were carried out for measurement of ACTH secretion and POMC
      gene expression. RESULTS: Incubation with AZA increased constitutive POMC
      expression and ACTH secretion by human corticotrope adenomas. The effect appeared
      most notable at 24 and 48 h with 1 MUM AZA. Incubation with AZA did not exert an
      additional stimulatory effect on CRH-stimulated POMC and ACTH. CONCLUSIONS: The
      present study shows that AZA increases POMC gene expression and ACTH secretion in
      human pituitary ACTH-secreting tumors. This can be taken to indicate that
      mechanisms set into motion by AZA play a role in the regulation of ACTH
      secretion/POMC expression in tumoral corticotropes and paves the way to further
      studies in Cushing's disease.

PMID- 24085686
TI  - Directed pathway evolution of the glyoxylate shunt in Escherichia coli for
      improved aerobic succinate production from glycerol.
AB  - alpha-Ketoglutarate is accumulated as the main byproduct during the aerobic
      succinate production from glycerol by Escherichia coli BL21(DE3) in minimal
      medium. To address this issue, here a strategy of directed pathway evolution was
      developed to enhance the alternative succinate production route-the glyoxylate
      shunt. Via the directed pathway evolution, the glyoxylate shunt was recruited as
      the primary anaplerotic pathway in a ppc mutant, which restored its viability in
      glycerol minimal medium. Subsequently, the operon sdhCDAB was deleted and the
      gene ppc was reverted in the evolved strain for succinate production. The
      resulting strain E2-Deltasdh-ppc produced 30 % more succinate and 46 % less alpha
      ketoglutarate than the control strain. A G583T mutation in gene icdA, which
      significantly decreased the activity of isocitrate dehydrogenase, was identified
      in the evolved strain as the main mutation responsible for the observed
      phenotype. Overexpression of alpha-ketoglutarate dehydrogenase complex in E2
      Deltasdh-ppc further reduced the amount of byproduct and improved succinate
      production. The final strain E2-Deltasdh-ppc-sucAB produced 366 mM succinate from
      1.3 M glycerol in minimal medium in fed-batch fermentation. The maximum and
      average succinate volumetric productivities were 19.2 and 6.55 mM h(-1),
      respectively, exhibiting potential industrial production capacity from the low
      priced substrate. 

PMID- 24085687
TI  - Clinical, epidemiologic, and laboratory aspects of methicillin-resistant
      Staphylococcus aureus infections.
AB  - Methicillin-resistant Staphylococcus aureus (MRSA) is a major pathogen
      responsible for both hospital and community onset disease. Resistance to
      methicillin in S. aureus is mediated by PBP2a, a penicillin-binding protein with
      low affinity to beta-lactams, encoded by the mecA gene. Accurate susceptibility
      testing of S. aureus isolates and screening of patients for colonization with
      MRSA are important tools to limit the spread of this organism. This review
      focuses on the clinical significance of MRSA infections and new approaches for
      the laboratory diagnosis and epidemiologic typing of MRSA strains. 

PMID- 24085689
TI  - Rapid methods for detection of MRSA in clinical specimens.
AB  - Antimicrobial susceptibility test methods such as disk diffusion, broth
      microdilution, and oxacillin screen plate require 24 h of incubation after having
      the organism growing in pure culture. Rapid and accurate identification of MRSA
      isolates is essential not only for patient care, but also for effective infection
      control programs to limit the spread of MRSA. In the last few years, several
      commercial rapid tests for detection of MRSA directly from nasal swabs and blood
      cultures have been developed for use in clinical laboratories. Real-time PCR and
      other molecular tests are gaining popularity as MRSA screening tests to identify
      patients who are candidates for contact precaution at the time of admission
      decreasing the risk for nosocomial transmission. These new methodologies have the
      advantage of a lower turnaround time than that of traditional culture and
      susceptibility testing and they are capable of detecting MRSA directly from nasal
      or wound swabs allowing rapid identification of colonized or infected patients.
      In addition, molecular methods able to detect and differentiate S. aureus and
      MRSA (SA/MRSA) directly from blood cultures are becoming a useful tool for rapid
      detection of bacteremia caused by MSSA and MRSA. This review focuses on the
      procedures for performing testing using rapid methods currently available for
      detection of MRSA directly from clinical specimens. 

PMID- 24085690
TI  - Immunofluorescence microscopy for the detection of surface antigens in
      methicillin-resistant Staphylococcus aureus (MRSA).
AB  - Immunofluorescence microscopy is a widely used laboratory method which allows
      detection and visualization of specific antigens. The method employs the
      specificity of antibodies to deliver fluorophore to a specific target and then
      visualize it with a microscope. The power of the technique is that it requires
      relatively little manipulation and relatively few bacterial cells, enabling the
      detection of antigen expression where other methods cannot, such as during an
      actual infection in an animal. Here, we apply the method to follow antigen
      expression on the surface of MRSA cells over time in in vivo infection models. 

PMID- 24085691
TI  - Internal transcribed spacer (ITS)-PCR identification of MRSA.
AB  - Polymerase chain reaction (PCR) analysis of the 16S-23S rRNA gene internal
      transcribed spacer (ITS) followed by microchip gel electrophoresis was useful for
      identification of staphylococci and for strain delineation of Staphylococcus
      aureus. In the study presented in this chapter, 74 ITS patterns were demonstrated
      among 1,188 isolated colonies of S. aureus: 55 patterns for methicillin
      susceptible S. aureus (MSSA), 4 patterns for methicillin-resistant S. aureus
      (MRSA), and 15 patterns for both MSSA and MRSA, highlighting the inability of ITS
      pattern analysis to differentiate the MSSA and MRSA strains. To overcome this
      problem, simultaneous PCR amplification of the ITS region and mecA gene was
      applied to isolated colonies of staphylococcus species and positive-testing blood
      culture bottles.

PMID- 24085688
TI  - Community-associated methicillin-resistant Staphylococcus aureus case studies.
AB  - Over the past decade, the emergence of community-associated methicillin-resistant
      Staphylococcus aureus (CA-MRSA) has changed the landscape of S. aureus infections
      around the globe. Initially recognized for its ability to cause disease in young
      and healthy individuals without healthcare exposures as well as for its distinct
      genotype and phenotype, this original description no longer fully encompasses the
      diversity of CA-MRSA as it continues to expand its niche. Using four case
      studies, we highlight a wide range of the clinical presentations and challenges
      of CA-MRSA. Based on these cases we further explore the globally polygenetic
      background of CA-MRSA with a special emphasis on generally less characterized
      populations. 

PMID- 24085692
TI  - Pulsed-field gel electrophoresis typing of Staphylococcus aureus isolates.
AB  - Pulsed-field gel electrophoresis (PFGE) is the most applied and effective genetic
      typing method for epidemiological studies and investigation of foodborne
      outbreaks caused by different pathogens, including Staphylococcus aureus. The
      technique relies on analysis of large DNA fragments generated by the cleavage of
      intact bacterial chromosomes with a rare cutting restriction enzyme, subsequently
      resolved by pulsed-field electrophoresis with periodic changes of the orientation
      of the electrical field across the gel. The high discriminatory power, improved
      reproducibility due to standardization of experimental protocols and data
      interpretation guidelines, and establishment of a national PFGE database of S.
      aureus profiles have made it a valuable means for global tracking of S. aureus
      infection sources and determination of genetic relatedness of outbreak isolates. 

PMID- 24085693
TI  - Multilocus sequence typing (MLST) of Staphylococcus aureus.
AB  - MLST is a widely accepted method of sequence-based typing that relies on analysis
      of relatively conserved genes that encode essential proteins. For Staphylococcus
      aureus the level of discrimination provided by MLST is sufficient to provide a
      relatively detailed picture of the global dissemination of the pathogen. The
      method is not restrictive in the precise methodology used to acquire the
      sequences, but the method of assigning types requires that the data be of high
      quality. Excellent web-based tools have been developed and are curated by the
      groups that launched MLST. These tools have allowed the scheme to be maintained
      as a coherent global asset and assist users in the analysis of their data.

PMID- 24085694
TI  - Staphylococcal Cassette Chromosome mec (SCCmec) analysis of MRSA.
AB  - Methicillin-susceptible S. aureus (MSSA) changes to methicillin-resistant S.
      aureus upon the acquisition of Staphylococcal Cassette Chromosome mec (SCCmec), a
      genomic island that encodes methicillin resistance. All SCCmec elements reported
      to date share four common characteristics: (1) carrying the mec gene complex
      (mec); (2) carrying the ccr gene complex (ccr); (3) being flanked by
      characteristic nucleotide sequences, inverted repeats, and direct repeats, at
      both ends; and (4) being integrated at the integration site sequence (ISS) for
      SCC, which is located at the 3'-end of orfX or at the extremity of the SCC
      element. SCCmec elements in S. aureus are classified into different types based
      on the combination of mec and ccr, which share variations, five classes in mec
      and eight in ccr. To date, at least 11 types of SCCmec elements have been
      identified. Regions other than mec and ccr within the SCCmec element are
      designated as "joining regions" (J-regions), which are classified into three
      subgroups, J1-3. Many J-region variants have been identified among the SCCmec
      elements of types I-V. We herein describe PCR methods to type SCCmec elements by
      first identifying the mec and ccr type, and then identifying genes in the J
      regions.

PMID- 24085695
TI  - Genetic interruption of target genes for investigation of virulence factors.
AB  - Recently, more emphasis has been given to understand molecular genetics and the
      contribution of a gene in the disease process. In fact, increased understanding
      of bacterial pathogenesis and intracellular communication has revealed many
      potential strategies for development of novel agents to treat bacterial
      infection. Therefore, to study the function and the involvement of a particular
      gene in pathogenesis, the inactivation or interruption is very important. In this
      section, various methods leading to inactivation of the gene in Staphylococcus
      aureus will be discussed. 

PMID- 24085696
TI  - Molecular analysis of staphylococcal superantigens.
AB  - Staphylococcal superantigens (SAgs) comprise a large family of exotoxins produced
      by Staphylococcus aureus strains. These exotoxins are important in a variety of
      serious human diseases, including menstrual and nonmenstrual toxic shock syndrome
      (TSS), staphylococcal pneumonia and infective endocarditis, and recently
      described staphylococcal purpura fulminans and extreme pyrexia syndrome. In
      addition, these SAg exotoxins are being increasingly recognized for their
      possible roles in many other human diseases, such as atopic dermatitis, Kawasaki
      syndrome, nasal polyposis, and certain autoimmune disorders. To clarify the full
      spectrum of human diseases caused by staphylococcal SAgs, it is necessary to have
      assays for them. At present there are 23 characterized, serologically distinct
      SAgs made by S. aureus: TSS toxin-1(TSST-1); staphylococcal enterotoxins (SEs) A,
      B (multiple variant forms exist), C (multiple minor variant forms exist), D, E,
      and G; and SE-like H, I, J, K, L, M, N, O, P, Q, R, S, T, U, V, and X. The most
      straightforward way to analyze S. aureus strains for SAgs is through polymerase
      chain reaction for their genes; we provide here our method for this analysis.
      Although it would be ideal to confirm that all of the same SAgs are produced by
      S. aureus strains that have the genes, antibody reagents for SAg detection are
      only available for TSST-1; SEs A-E and G; and enterotoxin-like proteins H, I, Q,
      and X. We provide a Western immunoblot procedure that allows in vitro
      quantification of these SAgs.

PMID- 24085697
TI  - Investigation of Staphylococcus aureus adhesion and invasion of host cells.
AB  - The continuous emergence of multidrug-resistant bacterial pathogens is a major
      problem in public health. Many mechanisms may be involved in such resistance in
      Staphylococcus aureus. Increasing data have shown that S. aureus can invade
      different types of host cells, which may contribute to escape from host immune
      defense as well as evade the toxicity of certain antibiotics. The organism
      produces various cell wall-associated molecules, particularly fibronectin-binding
      proteins, which are important for the bacterial cells to adhere to and
      internalize into the host cells. Thus, the expression levels of these factors
      affect the bacterial capacity of adhesion and invasion. In this study, we found
      that different human MRSA isolates possessed different abilities to adhere to and
      invade the epithelial cells. 

PMID- 24085698
TI  - Investigation of biofilm formation in clinical isolates of Staphylococcus aureus.
AB  - Invasive methicillin-resistant Staphylococcus aureus (MRSA) infections are often
      characterized by recalcitrance to antimicrobial therapy, which is a function not
      only of widespread antimicrobial resistance among clinical isolates, but also the
      capacity to form biofilms. Biofilms consist of ordered populations of bacterial
      colonies encased in a polysaccharide and/or proteinaceous matrix. This unique
      physiologic adaptation limits penetration of antimicrobial molecules and innate
      immune effectors to the infectious focus, increasing the likelihood of treatment
      failure and progression to chronic infection. Investigation of mechanisms of
      biofilm formation and dispersal, as well as the physiologic adaptations to the
      biofilm lifestyle, is therefore critical to developing new therapies to combat
      MRSA infections. In this chapter, we describe two in vitro methods for the
      investigation of staphylococcal biofilm formation, a microtiter plate-based assay
      of biofilm formation under static conditions and a flow cell-based assay of
      biofilm formation under fluid shear. We also detail an in vivo murine model of
      catheter-associated biofilm formation that is amenable to imaging and
      microbiologic analyses. Special consideration is given to the conditions
      necessary to support biofilm formation by clinical isolates of S. aureus. 

PMID- 24085699
TI  - Transcriptomic analysis of Staphylococcus aureus using microarray and advanced
      next-generation RNA-seq technologies.
AB  - The transcriptome has shown tremendous potential for the comprehensive
      investigation of gene expression profiles and transcriptional levels in
      comparative biology, the identification of regulatory mechanism of
      transcriptional regulators, and the evaluation of target gene for developing new
      chemotherapeutic agents, vaccine, and diagnostic methods. The traditional
      microarray and advanced next-generation RNA sequencing technologies (RNA-seq)
      provide powerful and effective tools for the determination of the transcriptome
      of bacterial cells. In this chapter, we provide a detailed protocol for
      scientists who want to investigate gene expression profiles by performing
      microarray and/or RNA-seq analysis, including different RNA purification methods,
      mRNA enrichment, decontamination, cDNA synthesis, fragmentation, biotin labeling
      for hybridization using Affymetrix Staphylococcus aureus chips, quantitative real
      time reverse transcription PCR, and RNA-seq data analysis.

PMID- 24085700
TI  - Proteomic approach to investigate pathogenicity and metabolism of methicillin
      resistant Staphylococcus aureus.
AB  - Over the last two decades, numerous genomes of pathogenic bacteria have been
      fully sequenced and annotated, while others are continuously being sequenced. To
      date, the sequences of more than 8,500 whole bacterial genomes are publicly
      available for research purposes. These efforts in high-throughput sequencing
      simultaneously to progresses in methods allowing to study whole transcriptome and
      proteome of bacteria provide the basis of comprehensive understanding of
      metabolism, adaptability to environment, regulation, resistance pathways, or
      pathogenicity mechanisms of bacterial pathogens. Staphylococcus aureus is a Gram
      positive human pathogen causing a wide variety of infections ranging from benign
      skin infection to life-threatening diseases. Furthermore, the spreading of
      multidrug-resistant isolates requiring the use of last barrier drugs has resulted
      in a particular attention of the medical and scientific community to this
      pathogen. We describe here proteomic methods to prepare, identify, and analyze
      protein fractions, which allow studying Staphylococcus aureus on the organism
      level. Besides evaluation of the whole bacterial transcriptome, this approach
      might contribute to the development of rapid diagnostic tests and to the
      identification of new drug targets to improve public health. 

PMID- 24085701
TI  - Metabolomic investigation of methicillin-resistant Staphylococcus aureus.
AB  - Metabolomics is becoming increasingly important as it provides a comprehensive
      analytical platform to better understand the biological functioning of a cell or
      organism. In recent years, microbial metabolomics has received much attention in
      research areas from new drug discovery to metabolic engineering. An efficient and
      accurate method to measure the intracellular metabolites of a specific microbial
      species is a key prerequisite for metabolome analysis. In this study, we describe
      a workflow focusing on the extraction and quantification of intracellular
      metabolites of Staphylococcus aureus. A filter-based bacteria sampling system was
      utilized to separate the media and bacteria; fast quenching with nitrogen was
      applied to prevent any metabolite leakage; a glass beads beater was used for
      intracellular metabolite extraction; and the LC-QTOF was combined to quantify the
      intracellular amino acids of S. aureus. This protocol is demonstrated to be an
      efficient method for analyzing the intracellular metabolites of S. aureus.

PMID- 24085702
TI  - Treatment of infections due to resistant Staphylococcus aureus.
AB  - This chapter reviews data on the treatment of infections caused by drug-resistant
      Staphylococcus aureus, particularly methicillin-resistant S. aureus (MRSA). This
      review covers findings reported in the English language medical literature up to
      January of 2013. Despite the emergence of resistant and multidrug-resistant S.
      aureus, we have seven effective drugs in clinical use for which little resistance
      has been observed: vancomycin, quinupristin-dalfopristin, linezolid, tigecycline,
      telavancin, ceftaroline, and daptomycin. However, vancomycin is less effective
      for infections with MRSA isolates that have a higher MIC within the susceptible
      range. Linezolid is probably the drug of choice for the treatment of complicated
      MRSA skin and soft tissue infections (SSTIs); whether it is drug of choice in
      pneumonia remains debatable. Daptomycin has shown to be non-inferior to either
      vancomycin or beta-lactams in the treatment of staphylococcal SSTIs, bacteremia,
      and right-sided endocarditis. Tigecycline was also non-inferior to comparator
      drugs in the treatment of SSTIs, but there is controversy about whether it is
      less effective than other therapeutic options in the treatment of more serious
      infections. Telavancin has been shown to be non-inferior to vancomycin in the
      treatment of SSTIs and pneumonia, but has greater nephrotoxicity. Ceftaroline is
      a broad-spectrum cephalosporin with activity against MRSA; it is non-inferior to
      vancomycin in the treatment of SSTIs. Clindamycin, trimethoprim-sulfamethoxazole,
      doxycycline, rifampin, moxifloxacin, and minocycline are oral anti-staphylococcal
      agents that may have utility in the treatment of SSTIs and osteomyelitis, but the
      clinical data for their efficacy is limited. There are also several drugs with
      broad-spectrum activity against Gm-positive organisms that have reached the phase
      II and III stages of clinical testing that will hopefully be approved for
      clinical use in the upcoming years: oritavancin, dalbavancin, omadacycline,
      tedizolid, delafloxacin, and JNJ-Q2. Thus, there are currently many effective
      drugs to treat resistant S. aureus infections and many promising agents in the
      pipeline. Nevertheless, S. aureus remains a formidable adversary, and despite our
      deep bullpen of potential therapies, there are still frequent treatment failures
      and unfortunate clinical outcomes. The following discussion summarizes the
      clinical challenges presented by MRSA, the clinical experience with our current
      anti-MRSA antibiotics, and the gaps in our knowledge on how to use these agents
      to most effectively combat MRSA infections.

PMID- 24085703
TI  - Anti-infective drug development for MRSA.
AB  - Staphylococcus aureus is an important pathogen linked to serious infections both
      in the hospital and the community settings. The challenge to treat infections
      caused by S. aureus has increased because of the emergence of multidrug-resistant
      strains such as methicillin-resistant S. aureus (MRSA). A limited spectrum of
      antibiotics is available to treat MRSA infections. This chapter reviews
      antimicrobial agents currently in use for the treatment of MRSA infections as
      well as agents that are in various stages of development. This chapter also
      reviews the alternate approaches that are being explored for the treatment of
      staphylococcal infections. 

PMID- 24085704
TI  - Animal models in drug development for MRSA.
AB  - One of the foremost challenges of drug discovery in any therapeutic area is that
      of solidifying the correlation between in vitro activity and clinical efficacy.
      Between these is the confirmation that affecting a particular target in vivo will
      lead to a therapeutic benefit. In antibacterial drug discovery, there is a key
      advantage from the start, since the targets are bacteria-therefore, it is simple
      to ascertain in vitro whether a drug has the desired effect, i.e., bacterial cell
      inhibition or killing, and to understand the mechanism by which that occurs. The
      downstream criteria, whether a compound reaches the infection site and achieves
      appropriately high levels to affect bacterial viability, can be evaluated in
      animal models of infection. In this way animal models of infection can be a
      highly valuable and predictive bridge between in vitro drug discovery and early
      clinical evaluation.The Gram-positive pathogen Staphylococcus aureus causes a
      wide variety of infections in humans (Archer, Clin Infect Dis 26:1179-1181, 1998)
      and has been said to be able to infect every tissue type. Fortunately, over the
      years a great deal of effort has been expended toward developing infection models
      in rodents using this organism, with good success. This chapter will describe the
      advantages, methods, and outcome measurements of the rodent models most used in
      drug discovery for S. aureus. Mouse models will be the focus of this chapter, as
      they are the most economical and thus most commonly used, but a rat infection
      model is included as well. 

PMID- 24085705
TI  - Gender-specific associations of perceived stress and coping strategies with C
      reactive protein in middle-aged and older men and women.
AB  - BACKGROUND: Perceived stress and coping strategies may influence the risk of
      cardiovascular disease through their possible association with inflammation, but
      data remain controversial for perceived stress or scanty for coping strategies.
      PURPOSE: We examined the associations of perceived stress and coping strategies
      with serum high-sensitivity C-reactive protein (CRP) in a Japanese general
      population. METHODS: This cross-sectional study included 2,971 men and 4,902
      women aged 40-69 years who were enrolled between 2005 and 2007. Subjects with
      possible inflammation-related disease, CRP levels >=3,000 ng/mL, or currently
      used analgesics or lipid-lowering drugs were excluded. Analyses were performed by
      gender with adjustment for lifestyle, socioeconomic, and psychosocial factors.
      RESULTS: Unexpectedly, elevated perceived stress was significantly associated
      with lower CRP levels in men (P trend < 0.001) but not in women (P trend = 0.90)
      after adjustment for age and covariates. Among five items of coping strategies
      evaluated, "disengagement" showed a significant inverse association with CRP in
      men only (P trend = 0.027). In addition, a possible interaction between
      "emotional support seeking" and perceived stress on CRP was detected in men (P
      interaction = 0.021); "emotional support seeking" was associated with lower CRP
      at the high stress level only (P trend = 0.028). CONCLUSIONS: Both perceived
      stress and coping strategies may be associated with systemic inflammation in
      Japanese men, yet caution must be exercised before accepting the stress
      inflammation-disease pathway.

PMID- 24085706
TI  - Viral suppression and antiretroviral medication adherence among alcohol using HIV
      positive adults.
AB  - BACKGROUND: Substance use is a known predictor of poor adherence to
      antiretroviral therapies (ART) in people living with human immunodeficiency virus
      (HIV)/acquired immunodeficiency syndrome. Less studied is the association between
      substance use and treatment outcomes, namely, suppression of HIV replication.
      METHODS: Adults living with HIV (N = 183) who reported alcohol use in the
      previous week and receiving ART were observed over a 12-month period.
      Participants completed computer interviews, monthly unannounced pill counts to
      monitor ART adherence, and daily cell-phone delivered interactive-text
      assessments for alcohol use. HIV viral load was collected at baseline and 12
      month follow-up from medical records. Analyses compared participants who had
      undetectable HIV viral loads at baseline and follow-up (sustained viral
      suppression) to those with unsustained viral suppression. Analyses also compared
      participants who were adherent to their medications (>85 % pills taken) over the
      year of observation to those who were nonadherent. RESULTS: Fifty-two percent of
      participants had unsustained viral suppression; 47 % were ART nonadherent.
      Overall results failed to demonstrate alcohol use as a correlate of sustained
      viral suppression or treatment adherence. However, alcohol use was associated
      with nonadherence among participants who did not have sustained viral
      suppression; nonadherence in unsustained viral suppression patients was related
      to drinking on fewer days of assessment, missing medications when drinking, and
      drinking socially. CONCLUSIONS: Poor HIV treatment outcomes and nonadherence were
      prevalent among adults treated for HIV infection who drink alcohol. Drinking in
      relation to missed medications and drinking in social settings are targets for
      interventions among alcohol drinkers at greatest risk for poor treatment
      outcomes.

PMID- 24085707
TI  - Clinical Presentation and Positive Outcome of Two Siblings with Holocarboxylase
      Synthetase Deficiency Caused by a Homozygous L216R Mutation.
AB  - Purpose The L216R mutation, seen in individuals of Polynesian descent, is
      considered one of the most severe mutations associated with holocarboxylase
      synthetase (HLCS) deficiency and is regarded as being unresponsive to biotin.
      This report describes the presentation and outcome in two surviving siblings,
      homozygous for this highly lethal mutation. Methods and results Both cases had
      perinatal head imaging findings of brain hemorrhage and subependymal cysts. Both
      had metabolic decompensation within 24 h after birth consisting of metabolic
      acidosis, lactic acidosis, and thrombocytopenia. Biochemical profiles were
      consistent with HLCS deficiency, and genetic analysis confirmed homozygosity for
      the L216R mutation. After resolution of neonatal metabolic crisis, dosing of
      biotin was titrated on an outpatient basis to primarily control dermatitis. The
      eldest is currently on 1.2 g of oral biotin daily, well above any dose previously
      reported to treat HLCS deficiency. To date, neither patient has required hospital
      readmission for acute metabolic decompensation. At the age of 7, the eldest child
      is, to our knowledge, the oldest patient ever described in the literature who is
      homozygous for the L216R mutation. She has mild intellectual disability.
      Conclusion This report contrasts previous reports of poor outcomes and neonatal
      deaths in homozygous L216R patients. We also provide data on the potential upper
      tolerable limit of biotin. These cases suggest that the outcome of HCLS
      deficiency due to a homozygous L216R mutation, when diagnosed and treated early
      with high-level neonatal care and biotin, may not be as severe as previously
      reported. 

PMID- 24085709
TI  - Endoscopic biopsy on patients taking antiplatelet agents: how much do we follow
      BSG, ASGE or ESGE guidelines?

PMID- 24085710
TI  - Reflections on political involvement.

PMID- 24085708
TI  - The pepper patatin-like phospholipase CaPLP1 functions in plant cell death and
      defense signaling.
AB  - Phospholipases hydrolyze phospholipids into fatty acids and other lipophilic
      substances. Phospholipid signaling is crucial for diverse cellular processes in
      plants. However, the precise role of phospholipases in plant cell death and
      defense signaling is not fully understood. Here, we identified a pepper (Capsicum
      annuum) patatin-like phospholipase (CaPLP1) gene that is transcriptionally
      induced in pepper leaves by avirulent Xanthomonas campestris pv. vesicatoria
      (Xcv) infection. CaPLP1 containing an N-terminal signal peptide localized to the
      cytoplasm and plasma membrane, leading to the secretion into the apoplastic
      regions. Silencing of CaPLP1 in pepper conferred enhanced susceptibility to Xcv
      infection. Defense responses to Xcv, including the generation of reactive oxygen
      species (ROS), hypersensitive cell death and the expression of the salicylic acid
      (SA)-dependent marker gene CaPR1, were compromised in the CaPLP1-silenced pepper
      plants. Transient expression of CaPLP1 in pepper leaves induced the accumulation
      of fluorescent phenolics, expression of the defense marker genes CaPR1 and
      CaSAR82A, and generation of ROS, ultimately leading to the hypersensitive cell
      death response. Overexpression (OX) of CaPLP1 in Arabidopsis also conferred
      enhanced resistance to Pseudomonas syringae pv. tomato (Pst) and Hyaloperonospora
      arabidopsidis infection. CaPLP1-OX leaves showed reduced Pst growth, enhanced ROS
      burst and electrolyte leakage, induction of the defense response genes AtPR1,
      AtRbohD and AtGST, as well as constitutive activation of both the SA-dependent
      gene AtPR1 and the JA-dependent gene AtPDF1.2. Together, these results suggest
      that CaPLP1 is involved in plant defense and cell death signaling in response to
      microbial pathogens. 

PMID- 24085711
TI  - Rinne revisited: steel versus aluminum tuning forks.
AB  - OBJECTIVE: (1) Determine whether tuning fork material (aluminum vs stainless
      steel) affects Rinne testing in the clinical assessment of conductive hearing
      loss (CHL). (2) Determine the relative acoustic and mechanical outputs of 512-Hz
      tuning forks made of aluminum and stainless steel. STUDY DESIGN: Prospective,
      observational. SETTING: Outpatient otology clinic. SUBJECTS AND METHODS: Fifty
      subjects presenting May 2011 to May 2012 with negative or equivocal Rinne in at
      least 1 ear and same-day audiometry. Rinne test results using aluminum and steel
      forks were compared and correlated with the audiometric air-bone gap. Bench top
      measurements using sound-level meter, microphone, and artificial mastoid.
      RESULTS: Patients with CHL were more likely to produce a negative Rinne test with
      a steel fork than with an aluminum fork. Logistic regression revealed that the
      probability of a negative Rinne reached 50% at a 19 dB air-bone gap for stainless
      steel versus 27 dB with aluminum. Bench top testing revealed that steel forks
      demonstrate, in effect, more comparable air and bone conduction efficiencies
      while aluminum forks have relatively lower bone conduction efficiency.
      CONCLUSION: We have found that steel tuning forks can detect a lesser air-bone
      gap compared to aluminum tuning forks. This is substantiated by observations of
      clear differences in the relative acoustic versus mechanical outputs of steel and
      aluminum forks, reflecting underlying inevitable differences in acoustic versus
      mechanical impedances of these devices, and thus efficiency of coupling
      sound/vibratory energy to the auditory system. These findings have clinical
      implications for using tuning forks to determine candidacy for stapes surgery.

PMID- 24085712
TI  - Biomechanics of the monopedicle skin flap.
AB  - OBJECTIVE: The design and implementation of skin flaps remains a puzzle for the
      reconstructive surgeon. The objective of the present study is to use finite
      element (FE) analysis to characterize and understand the biomechanics of the
      monopedicle skin flap design. STUDY DESIGN: The current study uses a nonlinear
      hyperelastic FE model of the human skin to understand the biomechanics of
      monopedicle-based flap designs as geometric flap parameters are varied. SETTING:
      In silico. SUBJECTS AND METHODS: The simulation included the displacement
      loading, stitching, and relaxation of various forms of the flap design. Stress
      and strain outcomes, previously correlated with scarring, necrosis, and blood
      perfusion, are reported for a basic monopedicle design as well as a number of
      modifications to this design. RESULTS: The results suggest that the length of the
      monopedicle flap should not exceed 3 times the size of the defect, as the benefit
      in reducing principal strain (deformation) is diminished beyond this point.
      Further, to minimize skin strain, the ideal Burrow's triangle size can be
      described as proportional to flap length and inversely proportional to defect
      height, according to a linear function. CONCLUSION: The ideal flap design should
      attempt to minimize not only the stress in the skin, but the size of the
      incisions and the degree of undermining. The results of our analyses provide
      guidance to increase the general understanding of monopedicle flap mechanics and
      provide context for the clinician and insight into designing a better monopedicle
      flap for individual situations.

PMID- 24085713
TI  - Relationship of race/ethnicity with door-to-balloon time and mortality in
      patients undergoing primary percutaneous coronary intervention for ST-elevation
      myocardial infarction: findings from Get With the Guidelines-Coronary Artery
      Disease.
AB  - BACKGROUND: Prior studies have described racial/ethnic disparities in door-to
      balloon (DTB) time for patients undergoing primary percutaneous coronary
      intervention (PCI). We sought to compare DTB time between different racial/ethnic
      groups undergoing primary PCI for ST-elevation myocardial infarction in Get With
      the Guidelines (GWTG). HYPOTHESIS: There may be differences in D2B time
      associated with race/ethnicity. METHODS: We identified 7445 white (n = 6365),
      African American (n = 568), and Hispanic (n = 512) patients undergoing primary
      PCI. RESULTS: There were no differences in the median DTB time between white (74
      minutes; intraquartile range [IQR], 54-99), African American (77 minutes; IQR, 57
      100), and Hispanic (75 minutes; IQR, 56-100) (P = 0.13) patients. There were no
      crude differences in DTB time <=90 minutes; however, after adjusting for
      confounders, African American race was associated with lower odds of DTB time
      <=90 minutes (odds ratio [OR]: 0.84; 95% confidence interval [CI]: 0.70-0.99; P =
      0.04). This association was seen in African American males (OR: 0.66; 95% CI:
      0.55-0.80) but not African American females (OR: 1.27; 95% CI: 0.96-1.68).
      Overall, Hispanic ethnicity was not associated with a difference in DTB time <=90
      minutes (OR: 0.98; 95% CI: 0.77-1.25; P = 0.88); although Hispanic males did have
      a slightly longer median DTB time compared with whites. During the study, the
      proportion of patients with DTB times <=90 minutes increased for all groups, and
      mortality was similar between groups (white 3.8%, African American 3.0%, Hispanic
      4.1%, P = 0.62). CONCLUSIONS: In GWTG-Coronary Artery Disease, small differences
      in DTB times persist among different races/ethnicities. However, the proportion
      achieving DTB times <=90 minutes has increased substantially for all patients
      over time, and there was no association between race/ethnicity and in-hospital
      mortality.

PMID- 24085714
TI  - Bilateral hearing loss after dichloromethane poisoning: a case report.
AB  - Dichloromethane is a widely used organic solvent. Occupational exposure to
      dichloromethane is frequent and can result in both acute and chronic toxicity,
      affecting mostly the central nervous system, directly or through its metabolite,
      carbon monoxide. The effects of dichloromethane on the peripheral nervous system
      are debated. Here we report the case of a 37-year-old woman who was accidentally
      exposed to dichloromethane. In the days following the incident she experienced
      bilateral hypoacusis. Hearing loss regressed after 25 days treatment with
      hyperbaric oxygen. This is the first report of sudden hearing loss after acute
      exposure to dichloromethane, suggesting a possible toxic effect of this solvent
      on the auditory system.

PMID- 24085715
TI  - Playing violent video games increases intergroup bias.
AB  - Previous research has shown how, why, and for whom violent video game play is
      related to aggression and aggression-related variables. In contrast, less is
      known about whether some individuals are more likely than others to be the target
      of increased aggression after violent video game play. The present research
      examined the idea that the effects of violent video game play are stronger when
      the target is a member of an outgroup rather than an ingroup. In fact, a
      correlational study revealed that violent video game exposure was positively
      related to ethnocentrism. This relation remained significant when controlling for
      trait aggression. Providing causal evidence, an experimental study showed that
      playing a violent video game increased aggressive behavior, and that this effect
      was more pronounced when the target was an outgroup rather than an ingroup
      member. Possible mediating mechanisms are discussed. 

PMID- 24085717
TI  - William Dawson at the Maudsley.

PMID- 24085718
TI  - Deep sleep therapy in Australia.

PMID- 24085719
TI  - The effect of group music therapy on anxiety, depression and quality of life in
      older adults with psychiatric disorders.

PMID- 24085720
TI  - Tardive dyskinesia with atypical antipsychotics in youth.

PMID- 24085721
TI  - Antidepressants and tamoxifen: interaction concerns.

PMID- 24085733
TI  - Schizophrenia, poor physical health and physical activity: evidence-based
      interventions are required to reduce major health inequalities.
AB  - In schizophrenia, life expectancy is reduced by 20 years, primarily due to
      cardiovascular disease (CVD). Physical activity modifies CVD risk factors, but
      physical activity levels are low in this patient group. We urgently need evidence
      based interventions that increase physical activity to improve health and reduce
      premature mortality in people with schizophrenia. 

PMID- 24085734
TI  - Towards clinically useful neuroimaging in psychiatric practice.
AB  - When psychiatrists see a patient, they consider a diagnosis, estimate a prognosis
      and treat accordingly, but very few of these decisions are informed by objective
      tests. Recent advances in neuroimaging data analysis have shown that brain scans
      can make powerful diagnostic and prognostic predictions in patients with
      psychosis and depression. 

PMID- 24085735
TI  - Running to catch up: rapid generation of evidence for interventions in learning
      disability services.
AB  - Few high-quality trials have been conducted in intellectual disability mental
      health. Trials such as Willner et al's have a 'close-to-market' focus. I argue
      that rapid generation of evidence for individuals with intellectual disability is
      the priority, alongside a new research focus on mental health in those with
      severe intellectual disability. 

PMID- 24085736
TI  - Difficulties in implementing supported employment for people with severe mental
      health problems.
AB  - People with severe mental health problems have low rates of open employment.
      Despite good evidence for the effectiveness of Individual Placement and Support
      (IPS), these schemes are not widely implemented. Their implementation is hampered
      by clinician and societal attitudes and the effect of organisational context on
      implementing IPS schemes with sufficient fidelity. 

PMID- 24085738
TI  - Effective suicide prevention measures for teenagers in Japan.

PMID- 24085737
TI  - Treatment for mild cognitive impairment: systematic review.
AB  - BACKGROUND: More people are presenting with mild cognitive impairment (MCI),
      frequently a precursor to dementia, but we do not know how to reduce
      deterioration. AIMS: To systematically review randomised controlled trials (RCTs)
      evaluating the effects of any intervention for MCI on cognitive,
      neuropsychiatric, functional, global outcomes, life quality or incident dementia.
      METHOD: We reviewed 41 studies fitting predetermined criteria, assessed validity
      using a checklist, calculated standardised outcomes and prioritised primary
      outcome findings in placebo-controlled studies. RESULTS: The strongest evidence
      was that cholinesterase inhibitors did not reduce incident dementia. Cognition
      improved in single trials of: a heterogeneous psychological group intervention
      over 6 months; piribedil, a dopamine agonist over 3 months; and donepezil over 48
      weeks. Nicotine improved attention over 6 months. There was equivocal evidence
      that Huannao Yicong improved cognition and social functioning. CONCLUSIONS: There
      was no replicated evidence that any intervention was effective. Cholinesterase
      inhibitors and rofecoxib are ineffective in preventing dementia. Further good
      quality RCTs are needed and preliminary evidence suggests these should include
      trials of psychological group interventions and piribedil.

PMID- 24085739
TI  - Authors' reply.

PMID- 24085741
TI  - Sensory over-responsivity in adults with autism spectrum conditions.
AB  - Anecdotal reports and empirical evidence suggest that sensory processing issues
      are a key feature of autism spectrum conditions. This study set out to
      investigate whether adults with autism spectrum conditions report more sensory
      over-responsivity than adults without autism spectrum conditions. Another goal of
      the study was to identify whether autistic traits in adults with and without
      autism spectrum conditions were associated with sensory over-responsivity. Adults
      with (n = 221) and without (n = 181) autism spectrum conditions participated in
      an online survey. The Autism Spectrum Quotient, the Raven Matrices and the
      Sensory Processing Scale were used to characterize the sample. Adults with autism
      spectrum conditions reported more sensory over-responsivity than control
      participants across various sensory domains (visual, auditory, tactile,
      olfactory, gustatory and proprioceptive). Sensory over-responsivity correlated
      positively with autistic traits (Autism Spectrum Quotient) at a significant level
      across groups and within groups. Adults with autism spectrum conditions
      experience sensory over-responsivity to daily sensory stimuli to a high degree. A
      positive relationship exists between sensory over-responsivity and autistic
      traits. Understanding sensory over-responsivity and ways of measuring it in
      adults with autism spectrum conditions has implications for research and clinical
      settings. 

PMID- 24085742
TI  - A case of sarcoma most consistent with the desmoplastic small round cell tumor
      arising from the ileal mesentery.

PMID- 24085743
TI  - Five-year relative survival rate of cancer in the USA, Europe and Japan.

PMID- 24085745
TI  - Red cell distribution width identifies cerebral venous sinus thrombosis in
      patients with headache.
AB  - BACKGROUND: Diagnosing cerebral venous sinus thrombosis (CVST) in patients
      referring to emergency service or neurology outpatient unit with complaints of
      headache is a challenging task. Magnetic resonance (MR) venography is the gold
      standard, but there are limitations regarding its use. AIM: To evaluate the
      validity of red cell distribution width (RDW) in CVST diagnosis in patients
      presenting with headache. METHODS: A total of 138 patients comprising 37 patients
      with CVST and 101 control primer headache cases were included in this
      retrospective cross-sectional study. Control group consists of hospitalized
      patients with primary headache. Venous blood hemoglobin (Hb), platelet, mean
      corpuscular volume (MCV), RDW, fibrinogen, and vitamin B12 levels of the patients
      were recorded at the first referral. Diagnosis of CVST was established by MR
      venography. RESULTS: The RDW ratio of patients with a diagnosis of CVST was
      significantly higher than that in patients with primary headache (15.3 +/- 1.4 vs
      13.3 +/- 0.5; P <.0001). Fibrinogen and vitamin B12 levels were not significantly
      different between the 2 groups. In a total of 11 patients, there was more than 1
      thrombosis. In 21 of the patients with CVST, gene mutation was detected. There
      was no significant difference between the patients with and without mutations
      regarding RDW values. Diagnostic validity of RDW was found to be excellent in
      differentiating patients with CVST and primary headache (area under the curve =
      0.996; 95% CI: 0.990-1.000). Optimum RDW cutoff value was determined as 14.1%
      (sensitivity: 91.9%, specificity: 99%, positive predictive value: 92.8, negative
      predictive value: 0.082). CONCLUSION: We suppose that among patients presenting
      with the complaint of headache, RDW value may lead to diagnose CVST.

PMID- 24085746
TI  - Experience with vena cava filters at a large community hospital and level-I
      trauma center: indications, complications, and compliance barriers.
AB  - INTRODUCTION: Inferior vena cava filters (IVCF) are used liberally in clinical
      practice and have been associated with multiple complications. Herein, we present
      results from our institution. METHODS: Records of consecutive patients discharged
      between January 1, 2009 and 2012 were reviewed. Indications were subcategorized
      under absolute, relative, and prophylactic. Student t test and Kaplan-Meier
      survival analysis were employed. RESULTS: During this period, 254 vena cava
      filters (VCF) were placed. Of these, 65 were placed for absolute indication, 28
      for relative, and 161 for prophylaxis. Follow-up imaging was available for 96
      patients of which 15 showed complications. Successful retrieval of 19 filters was
      achieved. CONCLUSION: The study demonstrates that most IVCF are being placed for
      prophylaxis with low retrieval rate. This contradicts current recommendations.
      Moreover frequent migration and penetration of IVCF can lead to serious
      complications. Strict enforcement of IVCF placement guidelines and setting up of
      filter clinics for timely retrieval is suggested.

PMID- 24085744
TI  - Transgenic 6F tomatoes act on the small intestine to prevent systemic
      inflammation and dyslipidemia caused by Western diet and intestinally derived
      lysophosphatidic acid.
AB  - We recently reported that levels of unsaturated lysophosphatidic acid (LPA) in
      the small intestine significantly correlated with the extent of aortic
      atherosclerosis in LDL receptor-null (LDLR-/-) mice fed a Western diet (WD). Here
      we demonstrate that WD increases unsaturated (but not saturated) LPA levels in
      the small intestine of LDLR-/- mice and causes changes in small intestine gene
      expression. Confirmation of microarray analysis by quantitative RT-PCR showed
      that adding transgenic tomatoes expressing the apoA-I mimetic peptide 6F (Tg6F)
      to WD prevented many WD-mediated small intestine changes in gene expression. If
      instead of feeding WD, unsaturated LPA was added to chow and fed to the mice: i)
      levels of LPA in the small intestine were similar to those induced by feeding WD;
      ii) gene expression changes in the small intestine mimicked WD-mediated changes;
      and iii) changes in plasma serum amyloid A, total cholesterol, triglycerides, HDL
      cholesterol levels, and the fast-performance liquid chromatography lipoprotein
      profile mimicked WD-mediated changes. Adding Tg6F (but not control tomatoes) to
      LPA-supplemented chow prevented the LPA-induced changes. We conclude that: i) WD
      mediated systemic inflammation and dyslipidemia may be in part due to WD-induced
      increases in small intestine LPA levels; and ii) Tg6F reduces WD-mediated
      systemic inflammation and dyslipidemia by preventing WD-induced increases in LPA
      levels in the small intestine.

PMID- 24085747
TI  - miR-133 links to energy balance through targeting Prdm16.

PMID- 24085748
TI  - Network analysis: a new approach to study endocrine disorders.
AB  - Systems biology is the study of the interactions that occur between the
      components of individual cells - including genes, proteins, transcription
      factors, small molecules, and metabolites, and their relationships to complex
      physiological and pathological processes. The application of systems biology to
      medicine promises rapid advances in both our understanding of disease and the
      development of novel treatment options. Network biology has emerged as the
      primary tool for studying systems biology as it utilises the mathematical
      analysis of the relationships between connected objects in a biological system
      and allows the integration of varied 'omic' datasets (including genomics,
      metabolomics, proteomics, etc.). Analysis of network biology generates
      interactome models to infer and assess function; to understand mechanisms, and to
      prioritise candidates for further investigation. This review provides an overview
      of network methods used to support this research and an insight into current
      applications of network analysis applied to endocrinology. A wide spectrum of
      endocrine disorders are included ranging from congenital hyperinsulinism in
      infancy, through childhood developmental and growth disorders, to the development
      of metabolic diseases in early and late adulthood, such as obesity and obesity
      related pathologies. In addition to providing a deeper understanding of diseases
      processes, network biology is also central to the development of personalised
      treatment strategies which will integrate pharmacogenomics with systems biology
      of the individual. 

PMID- 24085749
TI  - Impact of a diabetes control and management intervention on health care
      utilization in American Samoa.
AB  - OBJECTIVES: To examine the impact of a successful 12-month behavioral
      intervention to improve diabetes control on health care utilization in American
      Samoa. METHODS: A cluster-randomized design was used to assign 268 diabetes
      patients to a nurse-community health worker intervention or usual care.
      Hospitalizations, emergency department, and primary care physician visits were
      collected retrospectively for 1 year prior to, and during, the intervention to
      assess changes in health care utilization. The association of utilization changes
      with change in HbA1c during the intervention was assessed. RESULTS: Adjusted
      incidence rate ratios (RR) for primary care physician visits were significantly
      higher in the community health worker relative to the usual care group (RR =
      1.71; 95% CI, 1.25-2.33). There was no main intervention effect on emergency
      department utilization, but visits in the prior year modified the intervention
      effect on emergency department visits. Increased primary care physician
      utilization was associated with greater decreases in HbA1c (b = -0.10, SE = 0.04,
      p = 0.01). CONCLUSIONS: A culturally adapted community health worker diabetes
      intervention in American Samoa significantly increased primary care physician
      visits, and decreased emergency department visits among those with high emergency
      department usage in the prior year. These changes suggest important and
      beneficial impacts on health system utilization from the diabetes intervention in
      a low resource and high-risk population.

PMID- 24085750
TI  - Heart failure patients' attitudes, beliefs, expectations and experiences of self
      management strategies: a qualitative synthesis.
AB  - OBJECTIVES: To develop a model of heart failure patients' attitudes, beliefs,
      expectations, and experiences based on published qualitative research that could
      influence the development of self-management strategies. METHODS: A synthesis of
      19 qualitative research studies using the method of meta-ethnography. RESULTS:
      This synthesis offers a conceptual model of the attitudes, beliefs, and
      expectations of patients with heart failure. Patients experienced a sense of
      disruption before developing a mental model of heart failure. Patients' reactions
      included becoming a strategic avoider, a selective denier, a well-intentioned
      manager, or an advanced self-manager. Patients responded by forming self
      management strategies and finally assimilated the strategies into everyday life
      seeking to feel safe. DISCUSSION: This conceptual model suggests that there are a
      range of interplaying factors that facilitate the process of developing self
      management strategies. Interventions should take into account patients' concepts
      of heart failure and their subsequent reactions.

PMID- 24085751
TI  - Etude et suivi: rheumatoid arthritis in the 21st century.

PMID- 24085752
TI  - Challenges in defining quality of care for glucocorticoid-induced osteoporosis:
      defending good against perfect.

PMID- 24085753
TI  - Dosing of biologics in juvenile idiopathic arthritis: is the sky the limit?

PMID- 24085754
TI  - We still don't know how to taper glucocorticoids in rheumatoid arthritis, and we
      can do better.

PMID- 24085755
TI  - Corneal ulcerative features in rheumatoid arthritis.

PMID- 24085756
TI  - Ocular myositis occurring with NOD2-associated autoinflammatory disease.

PMID- 24085757
TI  - Charcot's arthropathy of the hip.

PMID- 24085758
TI  - Commentary on "The risky business of studying prognosis".

PMID- 24085759
TI  - Genetic interactions between BANK1 and BLK in Chinese patients with systemic
      lupus erythematosus.

PMID- 24085760
TI  - Sarcoidosis induced by tocilizumab: a paradoxical event?

PMID- 24085761
TI  - Subacute liver failure following anakinra treatment for adult-onset Still
      disease.

PMID- 24085762
TI  - PL-7 positive antisynthetase syndrome and pulmonary hypertension.

PMID- 24085763
TI  - Exome sequencing reveals a thrombopoietin ligand mutation in a Micronesian family
      with autosomal recessive aplastic anemia.
AB  - We recently identified 2 siblings afflicted with idiopathic, autosomal recessive
      aplastic anemia. Whole-exome sequencing identified a novel homozygous missense
      mutation in thrombopoietin (THPO, c.112C>T) in both affected siblings. This
      mutation encodes an arginine to cysteine substitution at residue 38 or residue 17
      excluding the 21-amino acid signal peptide of THPO receptor binding domain (RBD).
      THPO has 4 conserved cysteines in its RBD that form 2 disulfide bonds. Our in
      silico modeling predicts that introduction of a fifth cysteine may disrupt normal
      disulfide bonding to cause poor receptor binding. In functional assays, the
      mutant-THPO-containing media shows two- to threefold reduced ability to sustain
      UT7-TPO cells, which require THPO for proliferation. Both parents and a sibling
      with heterozygous R17C change have reduced platelet counts, whereas a sibling
      with wild-type sequence has normal platelet count. Thus, the R17C partial loss-of
      function allele results in aplastic anemia in the homozygous state and mild
      thrombocytopenia in the heterozygous state in our family. Together with the
      recent identification of THPO receptor (MPL) mutations and the effects of THPO
      agonists in aplastic anemia, our results have clinical implications in the
      diagnosis and treatment of patients with aplastic anemia and highlight a role for
      the THPO-MPL pathway in hematopoiesis in vivo. 

PMID- 24085764
TI  - Robust ZFN-mediated genome editing in adult hemophilic mice.
AB  - Monogenic diseases, including hemophilia, represent ideal targets for genome
      editing approaches aimed at correcting a defective gene. Here we report that
      systemic adeno-associated virus (AAV) vector delivery of zinc finger nucleases
      (ZFNs) and corrective donor template to the predominantly quiescent livers of
      adult mice enables production of high levels of human factor IX in a murine model
      of hemophilia B. Further, we show that off-target cleavage can be substantially
      reduced while maintaining robust editing by using obligate heterodimeric ZFNs
      engineered to minimize unwanted cleavage attributable to homodimerization of the
      ZFNs. These results broaden the therapeutic potential of AAV/ZFN-mediated genome
      editing in the liver and could expand this strategy to other nonreplicating cell
      types. 

PMID- 24085765
TI  - Eradicating acute myeloid leukemia in a Mll(PTD/wt):Flt3(ITD/wt) murine model: a
      path to novel therapeutic approaches for human disease.
AB  - The coexpression of the MLL partial tandem duplication (PTD) and the FLT3
      internal tandem duplication (ITD) mutations associate with a poor outcome in
      cytogenetically normal acute myeloid leukemia (AML). In mice, a double knock-in
      (dKI) of Mll(PTD/wt) and Flt3(ITD/wt) mutations induces spontaneous AML with an
      increase in DNA methyltransferases (Dnmt1, 3a, and 3b) and global DNA methylation
      index, thereby recapitulating its human AML counterpart. We determined that a
      regulator of Dnmts, miR-29b, is downregulated in bone marrow of dKI AML mice.
      Bortezomib exerted a dose-dependent increase in miR-29b expression in AML blasts
      ex vivo, followed by decreased Dnmts, reduced proliferation, and increased
      apoptosis. In vivo, bortezomib was not active against dKI AML, yet liposomal
      encapsulated bortezomib, as a single agent, reversed downregulation of miR-29b in
      vivo and induced a long-term (90-day) disease-free remission in 80% of dKI AML
      mice that exhibited high leukemic burden at the start of therapy, yet showed no
      signs of relapse at autopsy. Taken together, these data support that liposomal
      bortezomib, as a single agent, eradicates Mll(PTD/wt):Flt3(ITD/wt) AML in mouse
      and may represent a powerful and potentially curative approach to high-risk human
      disease. 

PMID- 24085767
TI  - Antisense-based RNA therapy of factor V deficiency: in vitro and ex vivo rescue
      of a F5 deep-intronic splicing mutation.
AB  - Antisense molecules are emerging as a powerful tool to correct splicing defects.
      Recently, we identified a homozygous deep-intronic mutation (F5 c.1296+268A>G)
      activating a cryptic donor splice site in a patient with severe coagulation
      factor V (FV) deficiency and life-threatening bleeding episodes. Here, we
      assessed the ability of 2 mutation-specific antisense molecules (a morpholino
      oligonucleotide [MO] and an engineered U7 small nuclear RNA [snRNA]) to correct
      this splicing defect. COS-1 and HepG2 cells transfected with a F5 minigene
      construct containing the patient's mutation expressed aberrant messenger RNA
      (mRNA) in excess of normal mRNA. Treatment with mutation-specific antisense MO (1
      5 uM) or a construct expressing antisense U7snRNA (0.25-2 ug) dose-dependently
      increased the relative amount of correctly spliced mRNA by 1 to 2 orders of
      magnitude, whereas control MO and U7snRNA were ineffective. Patient-derived
      megakaryocytes obtained by differentiation of circulating progenitor cells did
      not express FV, but became positive for FV at immunofluorescence staining after
      administration of antisense MO or U7snRNA. However, treatment adversely affected
      cell viability, mainly because of the transfection reagents used to deliver the
      antisense molecules. Our data provide in vitro and ex vivo proof of principle for
      the efficacy of RNA therapy in severe FV deficiency, but additional cytotoxicity
      studies are warranted. 

PMID- 24085766
TI  - Persistence of minimal residual disease in bone marrow predicts outcome in
      follicular lymphomas treated with a rituximab-intensive program.
AB  - We assessed the prognostic value of minimal residual disease (MRD) within the
      ML17638 phase 3 trial from the Fondazione Italiana Linfomi, investigating the
      role of rituximab maintenance in elderly follicular lymphoma (FL) patients after
      a brief first-line chemoimmunotherapy. MRD for the bcl-2/IgH translocation was
      determined on bone marrow cells in a centralized laboratory belonging to the Euro
      MRD consortium, using qualitative and quantitative polymerase chain reactions
      (PCRs). Of 234 enrolled patients, 227 (97%) were screened at diagnosis. A
      molecular marker (MM) was found in 51%. Patients with an MM were monitored at 8
      subsequent times. Of the 675 expected follow-up samples, 83% were analyzed.
      Conversion to PCR negativity predicted better progression-free survival (PFS) at
      all post-treatment times (eg, end of therapy: 3-year PFS, 72% vs 39%; P < .007).
      MRD was predictive in both maintenance (83% vs 60%; P < .007) and observation
      (71% vs 50%; P < .001) groups. PCR positivity at the end of induction was an
      independent adverse predictor (hazard ratio, 3.1; 95% confidence interval, 1.36
      7.07). MRD is a powerful independent outcome predictor in FL patients who receive
      rituximab-intensive programs, suggesting a need to investigate its value for
      decision-making. This trial was registered at www.clinicaltrial.gov as
      #NCT01144364. 

PMID- 24085768
TI  - JAK2V617F leads to intrinsic changes in platelet formation and reactivity in a
      knock-in mouse model of essential thrombocythemia.
AB  - The principal morbidity and mortality in patients with essential thrombocythemia
      (ET) and polycythemia rubra vera (PV) stems from thrombotic events. Most patients
      with ET/PV harbor a JAK2V617F mutation, but its role in the thrombotic diathesis
      remains obscure. Platelet function studies in patients are difficult to interpret
      because of interindividual heterogeneity, reflecting variations in the proportion
      of platelets derived from the malignant clone, differences in the presence of
      additional mutations, and the effects of medical treatments. To circumvent these
      issues, we have studied a JAK2V617F knock-in mouse model of ET in which all
      megakaryocytes and platelets express JAK2V617F at a physiological level,
      equivalent to that present in human ET patients. We show that, in addition to
      increased differentiation, JAK2V617F-positive megakaryocytes display greater
      migratory ability and proplatelet formation. We demonstrate in a range of assays
      that platelet reactivity to agonists is enhanced, with a concomitant increase in
      platelet aggregation in vitro and a reduced duration of bleeding in vivo. These
      data suggest that JAK2V617F leads to intrinsic changes in both megakaryocyte and
      platelet biology beyond an increase in cell number. In support of this
      hypothesis, we identify multiple differentially expressed genes in JAK2V617F
      megakaryocytes that may underlie the observed biological differences. 

PMID- 24085770
TI  - Impaired endothelial function after aneurysmal subarachnoid haemorrhage
      correlates with arginine:asymmetric dimethylarginine ratio.
AB  - BACKGROUND: Endothelial dysfunction might be involved in the development of
      cerebral vasospasm after aneurysmal subarachnoid haemorrhage (SAH). METHODS: This
      prospective observational study of 48 SAH subjects and 23 control subjects
      examined associations between reactive hyperaemia index (RHI) measured by
      peripheral arterial tonometry and plasma concentrations of S-100B protein,
      nitrite/nitrate, arginine, and asymmetric dimethyl arginine (ADMA). Clinical
      variables were flow velocity in the middle cerebral artery (VMCA), angiographic
      vasospasm, delayed neurological deficit, and 30 day survival. Five consecutive
      measurements were obtained at days 0-2, 3-5, 6-8, 9-11, and 12-15. RESULTS: RHI
      was 1.67 (0.46) at days 0-2 after SAH but increased at days 3-15 to the same
      levels as in controls (P<0.05 compared with days 0-2). RHI was lower in subjects
      who died before day 30 (P=0.07), but no trends were observed in relation to
      angiographic vasospasm or delayed neurological deficit. Both arginine and ADMA
      increased after SAH compared with days 0-2 (P<0.05). S-100B was highest in non
      survivors (P<0.01) and in subjects with neurological deficit (P<0.01). A positive
      correlation was found between RHI and arginine:ADMA ratio (r=0.43, P<0.005), but
      not with nitrite/nitrate, VMCA, or S-100B. CONCLUSIONS: Peripheral flow-mediated
      vasodilation is attenuated in the first days after SAH indicating acute systemic
      endothelial dysfunction. Impairment of endothelial function after SAH correlates
      with imbalance of the arginine/ADMA pathway.

PMID- 24085769
TI  - Structure of the factor VIII C2 domain in a ternary complex with 2 inhibitor
      antibodies reveals classical and nonclassical epitopes.
AB  - The factor VIII C2 domain is a highly immunogenic domain, whereby inhibitory
      antibodies develop following factor VIII replacement therapy for congenital
      hemophilia A patients. Inhibitory antibodies also arise spontaneously in cases of
      acquired hemophilia A. The structural basis for molecular recognition by 2
      classes of anti-C2 inhibitory antibodies that bind to factor VIII simultaneously
      was investigated by x-ray crystallography. The C2 domain/3E6 FAB/G99 FAB ternary
      complex illustrates that each antibody recognizes epitopes on opposing faces of
      the factor VIII C2 domain. The 3E6 epitope forms direct contacts to the C2 domain
      at 2 loops consisting of Glu2181-Ala2188 and Thr2202-Arg2215, whereas the G99
      epitope centers on Lys2227 and also makes direct contacts with loops Gln2222
      Trp2229, Leu2261-Ser2263, His2269-Val2282, and Arg2307-Gln2311. Each binding
      interface is highly electrostatic, with positive charge present on both C2
      epitopes and complementary negative charge on each antibody. A new model of
      membrane association is also presented, where the 3E6 epitope faces the
      negatively charged membrane surface and Arg2320 is poised at the center of the
      binding interface. These results illustrate the potential complexities of the
      polyclonal anti-factor VIII immune response and further define the "classical"
      and "nonclassical" types of antibody inhibitors against the factor VIII C2
      domain. 

PMID- 24085773
TI  - Clinician-trialist rounds: 18. Should young (and old!) clinician-trialists
      perform single-arm Phase II futility trials?

PMID- 24085772
TI  - The national drug abuse treatment clinical trials network data share project:
      website design, usage, challenges, and future directions.
AB  - BACKGROUND: There are many benefits of data sharing, including the promotion of
      new research from effective use of existing data, replication of findings through
      re-analysis of pooled data files, meta-analysis using individual patient data,
      and reinforcement of open scientific inquiry. A randomized controlled trial is
      considered as the 'gold standard' for establishing treatment effectiveness, but
      clinical trial research is very costly, and sharing data is an opportunity to
      expand the investment of the clinical trial beyond its original goals at minimal
      costs. PURPOSE: We describe the goals, developments, and usage of the Data Share
      website (http://www.ctndatashare.org) for the National Drug Abuse Treatment
      Clinical Trials Network (CTN) in the United States, including lessons learned,
      limitations, and major revisions, and considerations for future directions to
      improve data sharing. METHODS: Data management and programming procedures were
      conducted to produce uniform and Health Insurance Portability and Accountability
      Act (HIPAA)-compliant de-identified research data files from the completed trials
      of the CTN for archiving, managing, and sharing on the Data Share website.
      RESULTS: Since its inception in 2006 and through October 2012, nearly 1700
      downloads from 27 clinical trials have been accessed from the Data Share website,
      with the use increasing over the years. Individuals from 31 countries have
      downloaded data from the website, and there have been at least 13 publications
      derived from analyzing data through the public Data Share website. LIMITATIONS:
      Minimal control over data requests and usage has resulted in little information
      and lack of control regarding how the data from the website are used. Lack of
      uniformity in data elements collected across CTN trials has limited cross-study
      analyses. CONCLUSIONS: The Data Share website offers researchers easy access to
      de-identified data files with the goal to promote additional research and
      identify new findings from completed CTN studies. To maximize the utility of the
      website, ongoing collaborative efforts are needed to standardize the core
      measures used for data collection in the CTN studies with the goal to increase
      their comparability and to facilitate the ability to pool data files for cross
      study analyses.

PMID- 24085774
TI  - Marker Sequential Test (MaST) design.
AB  - BACKGROUND: New targeted anticancer therapies often benefit only a subset of
      patients with a given cancer. Definitive evaluation of these agents may require
      phase III randomized clinical trial designs that integrate evaluation of the new
      treatment and the predictive ability of the biomarker that putatively determines
      the sensitive subset. PURPOSE: We propose a new integrated biomarker design, the
      Marker Sequential Test (MaST) design, that allows sequential testing of the
      treatment effect in the biomarker subgroups and overall population while
      controlling the relevant type I error rates. METHODS: After defining the testing
      and error framework for integrated biomarker designs, we review the commonly used
      approaches to integrated biomarker testing. We then present a general form of the
      MaST design and describe how it can be used to provide proper control of false
      positive error rates for biomarker-positive and biomarker-negative subgroups. The
      operating characteristics of the MaST design are compared by analytical methods
      and simulations to the sequential subgroup-specific design that sequentially
      assesses the treatment effect in the biomarker subgroups. Practical aspects of
      MaST design implementation are discussed. RESULTS: The MaST design is shown to
      have higher power relative to the sequential subgroup-specific design in
      situations where the treatment effect is homogeneous across biomarker subgroups,
      while preserving the power for settings where treatment benefit is limited to
      biomarker-positive subgroup. For example, in the time-to-event setting considered
      with 30% biomarker-positive prevalence, the MaST design provides up to a 30%
      increase in power in the biomarker-positive and biomarker-negative subgroups when
      the treatment benefits all patients equally, while sustaining less than a 2% loss
      of power against alternatives where the benefit is limited to the biomarker
      positive subgroup. LIMITATIONS: The proposed design is appropriate for settings
      where it is reasonable to assume that the treatment will not be effective in the
      biomarker-negative patients unless it is effective in the biomarker-positive
      patients. CONCLUSION: The MaST trial design is a useful alternative to the
      sequential subgroup-specific design when it is important to consider the
      treatment effect in the biomarker-positive and biomarker-negative subgroups.

PMID- 24085775
TI  - Does recruitment for multicenter clinical trials improve dissemination and timely
      implementation of their results? A survey study from the Netherlands.
AB  - BACKGROUND RESULTS: from clinical trials are often slowly implemented. We studied
      whether participation in multicenter clinical trials improves reported
      dissemination, convincement, and subsequent implementation of its results.
      METHODS: We sent a web-based questionnaire to gynecologists, residents, nurses,
      and midwives in all obstetrics and gynecology departments in the Netherlands. For
      nine trials in perinatology, reproductive medicine, and gynecologic oncology, we
      asked the respondents whether they had knowledge of the results, were convinced
      by the results, and what percentage of their patients were treated according to
      the results of these trials. We compared the level of knowledge, convincement,
      and reported implementation of results in practice for the nine trials for
      respondents who worked in hospitals that had recruited for a trial with
      respondents who worked in a hospital that had not recruited for that trial. The
      reported implementation was restricted to six trials that showed decisive
      results. Results We analyzed 202 questionnaires from 83 departments in obstetrics
      and gynecology in the Netherlands (93% of all departments). The percentage of
      respondents who had worked in a hospital that recruited for a specific study
      varied between 8% and 71% per study and was 28% on average. The relative risk
      (RR) for knowledge of the study result for respondents who had worked in a
      recruiting hospital was for all studies positive and varied between 1.1 and 3.3
      (pooled RR: 1.8, 95% confidence interval (CI): 1.7-1.9). In general, health-care
      workers were convinced of trial results, independent of whether they had worked
      in a hospital that recruited for a trial or not (pooled RR: 1.02, 95% CI: 0.99
      1.05). Reported implementation of trial's results, that is, less than 20% were
      treated with unfavorable treatment according to study results, was better in
      hospitals that had recruited for those trials (pooled RR: 1.1, 95% CI: 1.02
      1.19). CONCLUSION: Participation in these multicenter clinical trials was
      associated with better knowledge about the trial's results, with a minor
      improvement of the reported implementation of the study results.

PMID- 24085776
TI  - Performance of two-stage continual reassessment method relative to an optimal
      benchmark.
AB  - BACKGROUND: The two-stage, likelihood-based continual reassessment method (CRM-L)
      entails the specification of a set of design parameters prior to the beginning of
      its use in a study. The impression of clinicians is that the success of model
      based designs, such as CRM-L, depends upon some of the choices made with regard
      to these specifications, such as the choice of parametric dose-toxicity model and
      the initial guess of toxicity probabilities. PURPOSE: In studying the efficiency
      and comparative performance of competing dose-finding designs for finite
      (typically small) samples, the nonparametric optimal benchmark is a useful tool.
      When comparing a dose-finding design to the optimal design, we are able to assess
      how much room there is for potential improvement. METHODS: The optimal method,
      based only on an assumption of monotonicity of the dose-toxicity function, is a
      valuable theoretical construct serving as a benchmark in theoretical studies,
      similar to that of a Cramer-Rao bound. We consider the performance of CRM-L under
      various design specifications and how it compares to the optimal design across a
      range of practical situations. RESULTS: Using simple recommendations for design
      specifications, the CRM-L will produce performances, in terms of identifying
      doses at and around the maximum tolerated dose (MTD), that are close to the
      optimal method on average over a broad group of dose-toxicity scenarios.
      LIMITATIONS: Although the simulation settings vary in the number of doses
      considered, the target toxicity rate, and the sample size, the results here are
      presented for a small, though widely used, set of two-stage CRM designs.
      CONCLUSIONS: Based on simulations here, and many others not shown, CRM-L is
      almost as accurate, in many scenarios, as the nonparametric optimal design. On
      average, there appears to be very little margin for improvement. Even if a finely
      tuned skeleton offers some improvement over a simple skeleton, the improvement is
      necessarily very small.

PMID- 24085777
TI  - Chemoprevention of head and neck cancer with celecoxib and erlotinib: results of
      a phase ib and pharmacokinetic study.
AB  - Epidermal growth factor receptor (EGFR) and COX-2 inhibitors synergistically
      inhibit head and neck squamous cell carcinoma tumorigenesis in preclinical
      studies. We conducted a phase I and pharmacokinetic study with the erlotinib and
      celecoxib combination in patients with advanced premalignant lesions. Thirty-six
      subjects with oral leukoplakia, mild, moderate, or severe dysplasia, or carcinoma
      in situ were screened for study participation; 12 consented and received therapy
      for a median of 5.38 months. Erlotinib was escalated following a standard 3+3
      design at 50, 75, and 100 mg orally daily and celecoxib was fixed at 400 mg twice
      daily for 6 months. Biopsy of lesions and cytobrush of normal mucosa were
      performed at baseline, 3, 6, and 12 months. Erlotinib pharmacokinetics were
      analyzed in 10 subjects. The maximum tolerated dose of erlotinib with celecoxib
      400 mg BID was 50 mg per day with skin rash being the main observed toxicity.
      Overall histologic response rate was 63% (complete response, 43%; partial
      response, 14%; stable disease, 29%; and disease progression, 14%). With median
      follow-up of 36 months, mean time to progression to higher-grade dysplasia or
      carcinoma was 25.4 months. Downregulation of EGFR and p-ERK in follow-up biopsies
      correlated with response to treatment. Larger average erlotinib V/F
      (approximately 308 L) and CL/F (8.3 L/h) compared with previous studies may be
      related to relatively large average bodyweights. Average erlotinib t1/2 was 25.6
      hours. Encouraging responses to the celecoxib and erlotinib combination
      correlated with EGFR pathway inhibition. Although erlotinib-related rash was the
      main limitation to dose escalation, the intervention was well tolerated.

PMID- 24085778
TI  - Lycopene metabolite, apo-10'-lycopenoic acid, inhibits diethylnitrosamine
      initiated, high fat diet-promoted hepatic inflammation and tumorigenesis in mice.
AB  - Obesity is associated with increased risk in hepatocellular carcinoma (HCC)
      development and mortality. An important disease control strategy is the
      prevention of obesity-related hepatic inflammation and tumorigenesis by dietary
      means. Here, we report that apo-10'-lycopenoic acid (APO10LA), a cleavage
      metabolite of lycopene at its 9',10'-double bond by carotene-9',10'-oxygenase,
      functions as an effective chemopreventative agent against hepatic tumorigenesis
      and inflammation. APO10LA treatment on human liver THLE-2 and HuH7 cells dose
      dependently inhibited cell growth and upregulated sirtuin 1 (SIRT1), a NAD(+)
      dependent protein deacetylase that may suppress hepatic carcinogenesis. This
      observed SIRT1 induction was associated with decreased cyclin D1 protein,
      increased cyclin-dependent kinase inhibitor p21 protein expression, and induced
      apoptosis. APO10LA supplementation (10 mg/kg diet) for 24 weeks significantly
      reduced diethylnitrosamine-initiated, high fat diet (HFD)-promoted hepatic
      tumorigenesis (50% reduction in tumor multiplicity; 65% in volume) and lung tumor
      incidence (85% reduction) in C57Bl/6J mice. The chemopreventative effects of
      APO10LA were associated with increased hepatic SIRT1 protein and deacetylation of
      SIRT1 targets, as well as with decreased caspase-1 activation and SIRT1 protein
      cleavage. APO10LA supplementation in diet improved glucose intolerance and
      reduced hepatic inflammation [decreased inflammatory foci, TNFalpha, interleukin
      (IL)-6, NF-kappaB p65 protein expression, and STAT3 activation] in HFD-fed mice.
      Furthermore, APO10LA suppressed Akt activation, cyclin D1 gene, and protein
      expression and promoted PARP protein cleavage in transformed cells within liver
      tumors. Taken together, these data indicate that APO10LA can effectively inhibit
      HFD-promoted hepatic tumorigenesis by stimulating SIRT1 signaling while reducing
      hepatic inflammation.

PMID- 24085779
TI  - Promoter sequence of Shiga toxin 2 (Stx2) is recognized in vivo, leading to
      production of biologically active Stx2.
AB  - Shiga toxins (Stx) are the main agent responsible for the development of
      hemolytic-uremic syndrome (HUS), the most severe and life-threatening systemic
      complication of infection with enterohemorrhagic Escherichia coli (EHEC) strains.
      We previously described Stx2 expression by eukaryotic cells after they were
      transfected in vitro with the stx2 gene cloned into a prokaryotic plasmid
      (pStx2). The aim of this study was to evaluate whether mammalian cells were also
      able to express Stx2 in vivo after pStx2 injection. Mice were inoculated by
      hydrodynamics-based transfection (HBT) with pStx2. We studied the survival,
      percentage of polymorphonuclear leukocytes in plasma, plasma urea levels, and
      histology of the kidneys and the brains of mice. Mice displayed a lethal dose
      related response to pStx2. Stx2 mRNA was recovered from the liver, and Stx2
      cytotoxic activity was observed in plasma of mice injected with pStx2. Stx2 was
      detected by immunofluorescence in the brains of mice inoculated with pStx2, and
      markers of central nervous system (CNS) damage were observed, including increased
      expression of glial fibrillary acidic protein (GFAP) and fragmentation of NeuN in
      neurons. Moreover, anti-Stx2B-immunized mice were protected against pStx2
      inoculation. Our results show that Stx2 is expressed in vivo from the wild stx2
      gene, reproducing pathogenic damage induced by purified Stx2 or secondary to EHEC
      infection. IMPORTANCE: Enterohemorrhagic Shiga toxin (Stx)-producing Escherichia
      coli (EHEC) infections are a serious public health problem, and Stx is the main
      pathogenic agent associated with typical hemolytic-uremic syndrome (HUS). In
      contrast to the detailed information describing the molecular basis for EHEC
      adherence to epithelial cells, very little is known about how Stx is released
      from bacteria in the gut, reaching its target tissues, mainly the kidney and
      central nervous system (CNS). In order to develop an efficient treatment for EHEC
      infections, it is necessary to understand the mechanisms involved in Stx
      expression. In this regard, the present study demonstrates that mammals can
      synthesize biologically active Stx using the natural promoter associated with the
      Stx-converting bacteriophage genome. These results could impact the comprehension
      of EHEC HUS, since local eukaryotic cells transduced and/or infected by
      bacteriophage encoding Stx2 could be an alternative source of Stx production.

PMID- 24085780
TI  - The two functional enoyl-acyl carrier protein reductases of Enterococcus faecalis
      do not mediate triclosan resistance.
AB  - Enoyl-acyl carrier protein (enoyl-ACP) reductase catalyzes the last step of the
      elongation cycle in the synthesis of bacterial fatty acids. The Enterococcus
      faecalis genome contains two genes annotated as enoyl-ACP reductases, a FabI-type
      enoyl-ACP reductase and a FabK-type enoyl-ACP reductase. We report that
      expression of either of the two proteins restores growth of an Escherichia coli
      fabI temperature-sensitive mutant strain under nonpermissive conditions. In vitro
      assays demonstrated that both proteins support fatty acid synthesis and are
      active with substrates of all fatty acid chain lengths. Although expression of E.
      faecalis fabK confers to E. coli high levels of resistance to the antimicrobial
      triclosan, deletion of fabK from the E. faecalis genome showed that FabK does not
      play a detectable role in the inherent triclosan resistance of E. faecalis.
      Indeed, FabK seems to play only a minor role in modulating fatty acid
      composition. Strains carrying a deletion of fabK grow normally without fatty acid
      supplementation, whereas fabI deletion mutants make only traces of fatty acids
      and are unsaturated fatty acid auxotrophs. IMPORTANCE: The finding that exogenous
      fatty acids support growth of E. faecalis strains defective in fatty acid
      synthesis indicates that inhibitors of fatty acid synthesis are ineffective in
      countering E. faecalis infections because host serum fatty acids support growth
      of the bacterium.

PMID- 24085781
TI  - Ordered kinetochore assembly in the human-pathogenic basidiomycetous yeast
      Cryptococcus neoformans.
AB  - Kinetochores facilitate interaction between chromosomes and the spindle
      apparatus. The formation of a metazoan trilayered kinetochore is an ordered event
      in which inner, middle, and outer layers assemble during disassembly of the
      nuclear envelope during mitosis. The existence of a similar strong correlation
      between kinetochore assembly and nuclear envelope breakdown in unicellular
      eukaryotes is unclear. Studies in the hemiascomycetous budding yeasts
      Saccharomyces cerevisiae and Candida albicans suggest that an ordered kinetochore
      assembly may not be evolutionarily conserved. Here, we utilized high-resolution
      time-lapse microscopy to analyze the localization patterns of a series of
      putative kinetochore proteins in the basidiomycetous budding yeast Cryptococcus
      neoformans, a human pathogen. Strikingly, similar to most metazoa but atypical of
      yeasts, the centromeres are not clustered but positioned adjacent to the nuclear
      envelope in premitotic C. neoformans cells. The centromeres gradually coalesce to
      a single cluster as cells progress toward mitosis. The mitotic clustering of
      centromeres seems to be dependent on the integrity of the mitotic spindle. To
      study the dynamics of the nuclear envelope, we followed the localization of two
      marker proteins, Ndc1 and Nup107. Fluorescence microscopy of the nuclear envelope
      and components of the kinetochore, along with ultrastructure analysis by
      transmission electron microscopy, reveal that in C. neoformans, the kinetochore
      assembles in an ordered manner prior to mitosis in concert with a partial opening
      of the nuclear envelope. Taken together, the results of this study demonstrate
      that kinetochore dynamics in C. neoformans is reminiscent of that of metazoans
      and shed new light on the evolution of mitosis in eukaryotes. IMPORTANCE:
      Successful propagation of genetic material in progeny is essential for the
      survival of any organism. A proper kinetochore-microtubule interaction is crucial
      for high-fidelity chromosome segregation. An error in this process can lead to
      loss or gain of chromosomes, a common feature of most solid cancers. Several
      proteins assemble on centromere DNA to form a kinetochore. However, significant
      differences in the process of kinetochore assembly exist between unicellular
      yeasts and multicellular metaozoa. Here, we examined the key events that lead to
      formation of a proper kinetochore in a basidiomycetous budding yeast,
      Cryptococcus neoformans. We found that, during the progression of the cell cycle,
      nonclustered centromeres gradually clustered and kinetochores assembled in an
      ordered manner concomitant with partial opening of the nuclear envelope in this
      organism. These events have higher similarity to mitotic events of metazoans than
      to those previously described in other yeasts.

PMID- 24085782
TI  - Staphylococcus aureus protein A promotes immune suppression.
AB  - Staphylococcus aureus is a prominent cause of human infections worldwide and is
      notorious for its ability to acquire resistance to antibiotics. Methicillin
      resistant S. aureus (MRSA), in particular, is endemic in hospitals and is the
      most frequent cause of community-associated bacterial infections in the United
      States. Inasmuch as treatment options for severe MRSA infections are limited,
      there is need for a vaccine that protects against such infections. However,
      recent efforts to generate a staphylococcal vaccine have met with little success
      in human clinical trials. These failures are somewhat puzzling, since the vaccine
      antigens tested promote opsonophagocytosis in vitro and confer protection in
      animal infection models. One possibility is that the pathogen inhibits (and/or
      fails to elicit) the development of protective immunity in humans. Indeed, S.
      aureus produces numerous molecules that can potentially promote immune evasion,
      including protein A (SpA), an immunoglobulin (Ig)-binding protein present on the
      bacterial surface and freely secreted into the extracellular environment. SpA
      binds the Fc region of antibody and the Fab regions of the B-cell receptor,
      processes that are known to block opsonophagocytosis and cause B-cell death in
      vitro. In a recent study, Falugi et al. [F. Falugi, H. K. Kim, D. M. Missiakas,
      and O. Schneewind, mBio 4(5):e00575-13, 2013] showed that vaccination with spa
      mutant S. aureus strains lacking antibody Fc- and/or Fab-binding capacity
      protects against subsequent challenge with the USA300 epidemic strain. The
      findings provide strong support for the idea that SpA promotes S. aureus immune
      evasion in vivo and form the foundation for a new approach in our efforts to
      develop a vaccine that prevents severe S. aureus infections.

PMID- 24085783
TI  - Atherosclerotic plaque identification by virtual histology intravascular
      ultrasound in a rabbit abdominal aorta model of vulnerable plaque.
AB  - This study aimed to evaluate the utility of virtual histology intravascular
      ultrasound (VH-IVUS) for recognizing vulnerable plaque compared to histological
      pathological analysis. Four-month-old New Zealand rabbits (n = 16) were randomly
      divided into two groups: one fed a high-fat diet and subjected to balloon injury
      (experimental, n = 10) and one fed a high-fat diet alone (control, n = 6). Blood
      lipid profiles of overnight-fasted rabbits were measured at week 2 (beginning of
      study) and week 12 (end of study). At week 12, experimental group rabbits
      underwent IVUS under anaesthesia. Rabbits were sacrificed and a 5-cm segment of
      the abdominal aorta was removed. Arterial sections were subjected to pathological
      and immunohistochemical analyses. Serum lipid levels increased in all rabbits fed
      with high-fat diet, with low-density lipid cholesterol (LDL-C) levels increasing
      the most. Levels of six biomarkers (high sensitivity C-reactive protein, matrix
      metalloproteinase-3, interleukin [IL]-1, IL-10, tumour necrosis factor-alpha, and
      oxidized [ox]-LDL) showed no differences between the two groups at week 2, but
      were higher in the experimental group at week 12. A total of 276 atherosclerotic
      plaques in the experimental group were analysed. VH-IVUS had sensitivities of 87%
      and 92% for detection of noncalcified and calcified thin-cap fibroatheromas,
      respectively. VH-IVUS correctly identified 85% and 89% of noncalcified and
      calcified fibroatheromas, respectively. For detection of pathological intimal
      thickening, VH-IVUS showed a sensitivity of 79% and positive predictive value of
      78%. Linear regression analysis showed a strong correlation between histology and
      VH-IVUS for the percent area of fibrous fibro-fatty tissue, necrotic calcified
      tissue, and confluent necrotic core. The intra-observer and inter-observer
      variability of the intimal and medial-adventitial boundaries was low. Endothelial
      injury followed by a high-fat diet in rabbits is a viable method for inducing
      atheroma, and VH-IVUS is a feasible, reproducible, and valuable means of
      vulnerable plaque identification in vivo. 

PMID- 24085784
TI  - Antiviral treatment improves disrupted peripheral B lymphocyte homeostasis in
      chronic hepatitis B virus-infected patients.
AB  - Disruption of peripheral blood B-cell homeostasis and variation of surface
      receptors occur with certain infections and autoimmune diseases. However, the
      impact of antiviral therapy on B-cell alteration during chronic hepatitis B (CHB)
      infection remains unclear. Our study aims to document the effects of B-cell
      alteration in CHB patients treated with tenofovir or adefovir. A total of 21 CHB
      patients and 10 healthy donors were recruited into the study. We identified B
      cell subsets by flow cytometry and observed changes in the B-cell repertoire of
      CHB patients upon tenofovir or adefovir antiviral treatment. The total and
      percent of B cells and CD5 + B-cell subsets were significantly increased in CHB
      patients compared to healthy donors. Total and percent of CD5 + B cells gradually
      decreased following the diminution of the HBV DNA load after tenofovir and
      adefovir treatment. Upon tenofovir treatment, the percent of memory CD27 + B
      cells was increased but the absolute number declined, whereas naive CD27- B cells
      declined in both percent and absolute number. In the adefovir treatment group,
      neither naive nor memory B cells were altered by the treatment. Furthermore, CHB
      patients displayed higher levels of activation markers (CD69 and CD24) and
      trended towards restored B-cell homeostasis after antiviral treatment. In
      conclusion, disrupted B-cell homeostasis is an important feature of CHB patients
      and is partially restored after control of viral replication by antiviral
      treatment. B-cell antiviral immunity is improved by restoring B-cell homeostasis
      and activation. 

PMID- 24085785
TI  - Characterization of squamous cell carcinoma in an organotypic culture via
      subsurface non-linear optical molecular imaging.
AB  - Tristetraprolin (TTP) is an RNA-binding protein which downregulates multiple
      cytokines that mediate progression of head and neck squamous cell carcinoma
      (HNSCC). We previously showed that HNSCC cells with shRNA-mediated knockdown of
      TTP are more invasive than controls. In this study, we use control and TTP
      deficient cells to present a novel subsurface non-linear optical molecular
      imaging method using a three-dimensional (3D) organotypic construct, and compare
      the live cell imaging data to histology of fixed tissue specimens. This
      manuscript describes how to prepare and image the novel organotypic system that
      closely mimics HNSCC in a clinical setting. The oral cancer equivalent (OCE)
      system allows HNSCC cells to stratify and invade beyond the basement membrane
      into underlying connective tissue prepared from decellularized human dermal
      tissue. The OCE model was inspired by tissue engineering strategies to prepare
      autologous transplants from human keratinocytes. Advantages of this method over
      previously used in vitro cancer models include the simulation of the basement
      membrane and complex connective tissue in the construct, in addition to the
      ability to track the 3D movement of live invading cells and quantify matrix
      destruction over time. The OCE model and novel live cell imaging strategy may be
      applied to study other types of 3D tissue constructs. 

PMID- 24085786
TI  - Intestinal GUCY2C prevents TGF-beta secretion coordinating desmoplasia and
      hyperproliferation in colorectal cancer.
AB  - Tumorigenesis is a multistep process that reflects intimate reciprocal
      interactions between epithelia and underlying stroma. However, tumor-initiating
      mechanisms coordinating transformation of both epithelial and stromal components
      are not defined. In humans and mice, initiation of colorectal cancer is
      universally associated with loss of guanylin and uroguanylin, the endogenous
      ligands for the tumor suppressor guanylyl cyclase C (GUCY2C), disrupting a
      network of homeostatic mechanisms along the crypt-surface axis. Here, we reveal
      that silencing GUCY2C in human colon cancer cells increases Akt-dependent TGF
      beta secretion, activating fibroblasts through TGF-beta type I receptors and
      Smad3 phosphorylation. In turn, activating TGF-beta signaling induces fibroblasts
      to secrete hepatocyte growth factor (HGF), reciprocally driving colon cancer cell
      proliferation through cMET-dependent signaling. Elimination of GUCY2C signaling
      in mice (Gucy2c(-/-)) produces intestinal desmoplasia, with increased reactive
      myofibroblasts, which is suppressed by anti-TGF-beta antibodies or genetic
      silencing of Akt. Thus, GUCY2C coordinates intestinal epithelial-mesenchymal
      homeostasis through reciprocal paracrine circuits mediated by TGF-beta and HGF.
      In that context, GUCY2C signaling constitutes a direct link between the
      initiation of colorectal cancer and the induction of its associated desmoplastic
      stromal niche. The recent regulatory approval of oral GUCY2C ligands to treat
      chronic gastrointestinal disorders underscores the potential therapeutic
      opportunity for oral GUCY2C hormone replacement to prevent remodeling of the
      microenvironment essential for colorectal tumorigenesis.

PMID- 24085787
TI  - Crizotinib inhibits metabolic inactivation of gemcitabine in c-Met-driven
      pancreatic carcinoma.
AB  - Pancreatic ductal adenocarcinoma (PDAC) remains a major unsolved health problem.
      Most drugs that pass preclinical tests fail in these patients, emphasizing the
      need of improved preclinical models to test novel anticancer strategies. Here, we
      developed four orthotopic mouse models using primary human PDAC cells genetically
      engineered to express firefly- and Gaussia luciferase, simplifying the ability to
      monitor tumor growth and metastasis longitudinally in individual animals with MRI
      and high-frequency ultrasound. In these models, we conducted detailed
      histopathologic and immunohistochemical analyses on paraffin-embedded pancreatic
      tissues and metastatic lesions in liver, lungs, and lymph nodes. Genetic
      characteristics were compared with the originator tumor and primary tumor cells
      using array-based comparative genomic hybridization, using frozen specimens
      obtained by laser microdissection. Notably, the orthotopic human xenografts in
      these models recapitulated the phenotype of human PDACs, including hypovascular
      and hypoxic areas. Pursuing genomic and immunohistochemical evidence revealed an
      increased copy number and overexpression of c-Met in one of the models; we
      examined the preclinical efficacy of c-Met inhibitors in vitro and in vivo. In
      particular, we found that crizotinib decreased tumor dimension, prolonged
      survival, and increased blood and tissue concentrations of gemcitabine,
      synergizing with a cytidine deaminase-mediated mechanism of action. Together,
      these more readily imaged orthotopic PDAC models displayed genetic,
      histopathologic, and metastatic features similar to their human tumors of origin.
      Moreover, their use pointed to c-Met as a candidate therapeutic target in PDAC
      and highlighted crizotinib and gemcitabine as a synergistic combination of drugs
      warranting clinical evaluation for PDAC treatment.

PMID- 24085789
TI  - The translational research impact scale: development, construct validity, and
      reliability testing.
AB  - Increasing emphasis is being placed on measuring return on research investment
      and determining the true impacts of biomedical research for medical practice and
      population health. This article describes initial progress on development of a
      new standardized tool for identifying and measuring impacts across research
      sites. The Translational Research Impact Scale (TRIS) is intended to provide a
      systematic approach to assessing impact levels using a set of 72 impact
      indicators organized into three broad research impact domains and nine
      subdomains. A validation process was conducted with input from a panel of 31
      experts in translational research, who met to define and standardize the
      measurement of research impacts using the TRIS. Testing was performed to estimate
      the reliability of the experts' ratings. The reliability was found to be high
      (ranging from .75 to .94) in all of the domains and most of the subdomains. A
      weighting process was performed assigning item weights to the individual
      indicators, so that composite scores can be derived.

PMID- 24085788
TI  - Enhancement of antitumor immunity in lung cancer by targeting myeloid-derived
      suppressor cell pathways.
AB  - Chemoresistance due to heterogeneity of the tumor microenvironment (TME) hampers
      the long-term efficacy of first-line therapies for lung cancer. Current
      combination therapies for lung cancer provide only modest improvement in
      survival, implicating necessity for novel approaches that suppress malignant
      growth and stimulate long-term antitumor immunity. Oxidative stress in the TME
      promotes immunosuppression by tumor-infiltrating myeloid-derived suppressor cells
      (MDSC), which inhibit host protective antitumor immunity. Using a murine model of
      lung cancer, we demonstrate that a combination treatment with gemcitabine and a
      superoxide dismutase mimetic targets immunosuppressive MDSC in the TME and
      enhances the quantity and quality of both effector and memory CD8(+) T-cell
      responses. At the effector cell function level, the unique combination therapy
      targeting MDSC and redox signaling greatly enhanced cytolytic CD8(+) T-cell
      response and further decreased regulatory T cell infiltration. For long-term
      antitumor effects, this therapy altered the metabolism of memory cells with self
      renewing phenotype and provided a preferential advantage for survival of memory
      subsets with long-term efficacy and persistence. Adoptive transfer of memory
      cells from this combination therapy prolonged survival of tumor-bearing
      recipients. Furthermore, the adoptively transferred memory cells responded to
      tumor rechallenge exerting long-term persistence. This approach offers a new
      paradigm to inhibit immunosuppression by direct targeting of MDSC function, to
      generate effector and persistent memory cells for tumor eradication, and to
      prevent lung cancer relapse.

PMID- 24085790
TI  - Commentary: when doing less is best.

PMID- 24085791
TI  - Acute bacterial sinusitis in children.
AB  - On the basis of strong research evidence, the pathogenesis of sinusitis involves
      3 key factors: sinusostia obstruction, ciliary dysfunction, and thickening of
      sinus secretions. On the basis of studies of the microbiology of otitis media, H
      influenzae is playing an increasingly important role in the etiology of
      sinusitis, exceeding that of S pneumoniae in some areas, and b-lactamase
      production by H influenzae is increasing in respiratory isolates in the United
      States. On the basis of some research evidence and consensus,the presentation of
      acute bacterial sinusitis conforms to 1 of 3 predicable patterns; persistent,
      severe, and worsening symptoms. On the basis of some research evidence and
      consensus,the diagnosis of sinusitis should be made by applying strict clinical
      criteria. This approach will select children with upper respiratory infection
      symptoms who are most likely to benefit from an antibiotic. On the basis of some
      research evidence and consensus,imaging is not indicated routinely in the
      diagnosis of sinusitis. Computed tomography or magnetic resonance imaging
      provides useful information when complications of sinusitis are suspected. On the
      basis of some research evidence and consensus,amoxicillin-clavulanate should be
      considered asa first-line agent for the treatment of sinusitis.

PMID- 24085792
TI  - Pneumonia.

PMID- 24085793
TI  - Hernias and hydroceles.
AB  - Inguinoscrotal abnormalities in children are best understood by understanding the
      embryology of testicular descent and the failure of the processus vaginalis to
      properly obliterate. The inguinal hernia, communicating hydrocele, hydrocele of
      the spermatic cord, and scrotal hydrocele should be differentiated based on a
      history and physical examination in most cases, with selective use of
      ultrasonography. The urgency to surgically correct these entities depends on the
      nature of the hernia or hydrocele and the likelihood of incarceration or
      spontaneous resolution. Open standard herniorrhaphy remains the most common
      surgical approach, and concurrent transinguinal laparoscopy allows quick and
      accurate inspection of the contralateral internal inguinal ring and the need for
      bilateral repair of an inguinal hernia.

PMID- 24085794
TI  - Index of suspicion.

PMID- 24085795
TI  - Visual diagnosis: 10-year-old girl with fever and altered mental status.
AB  - Necrotizing soft tissue infections are rare but deadly infections. Diagnosis is
      made clinically with a high index of suspicion. Definitive treatment includes
      emergency surgical debridement, broad-spectrum antibiotics, and supportive care
      in the intensive care unit. The initial antibiotic regimen should be broad and
      cover gram-negative, anaerobic, and gram-positive organisms. Increased mortality
      is associated with delay in operative intervention.

PMID- 24085796
TI  - Complementary, holistic, and integrative medicine: autism spectrum disorder and
      gluten- and casein-free diet.
AB  - On the basis of review of the published literature,limitations in current data do
      not support the use ofa gluten-free and casein-free diet (gfcf-d) asa primary
      autism spectrum disorder (ASD) treatment.(13)(25)(26)(36) On the basis of
      clinical opinion, given the popularity of parents seeking a gfcf-d for their
      children with ASD, clinicians should acknowledge family's concerns and provide
      appropriate information about a gfcf-d toguide them and prevent possible harm.

PMID- 24085797
TI  - Characteristics of microRNAs enriched in specific cell types and primary tissue
      types in solid organs.
AB  - Knowledge of miRNA expression and function in specific cell types in solid organs
      is limited because of difficulty in obtaining appropriate specimens. We used
      laser capture microdissection to obtain nine tissue regions from rats, including
      the nucleus of the solitary tract, hypoglossal motor nucleus, ventral respiratory
      column/pre-Botzinger complex, and midline raphe nucleus from the brain stem,
      myocardium and coronary artery from the heart, and glomerulus, proximal
      convoluted tubule, and medullary thick ascending limb from the kidney. Each
      tissue region consists of or is enriched for a specific cell type. Differential
      patterns of miRNA expression obtained by deep sequencing of minute amounts of
      laser-captured cells were highly consistent with data obtained from real-time PCR
      analysis. miRNA expression patterns correctly clustered the specimens by tissue
      regions and then by primary tissue types (neural, muscular, or epithelial). The
      aggregate difference in miRNA profiles between tissue regions that contained the
      same primary tissue type was as large as one-half of the aggregate difference
      between primary tissue types. miRNAs differentially expressed between primary
      tissue types are more likely to be abundant miRNAs, while miRNAs differentially
      expressed between tissue regions containing the same primary tissue type were
      distributed evenly across the abundance spectrum. The tissue type-enriched miRNAs
      were more likely to target genes enriched for specific functional categories
      compared with either cell type-enriched miRNAs or randomly selected miRNAs. These
      data indicate that the role of miRNAs in determining characteristics of primary
      tissue types may be different than their role in regulating cell type-specific
      functions in solid organs. 

PMID- 24085798
TI  - Mechanisms of platelet-stimulated colon cancer invasion: role of clusterin and
      thrombospondin 1 in regulation of the P38MAPK-MMP-9 pathway.
AB  - Platelets have been implicated in colon cancer metastasis and prognosis but the
      underlying molecular mechanisms remain unclear. We evaluated the role of the
      different mitogen-activated protein kinase (MAPK) pathways in platelet-stimulated
      matrix metalloproteinase-9 (MMP-9) generation and colon cancer invasion. In
      addition, proteins released during platelet-tumour cell interactions were
      studied. For this purpose, interactions of Caco-2 and HT29 cells with platelets
      were studied using scanning electron microscopy, aggregometry, flow cytometry and
      cell invasion chambers. Quantitative PCR and zymography were used to study MMP-9
      gene expression and activity, respectively, whereas western blot was used to
      study p38MAPK. Finally, the origin of proteins during platelet-cancer cell
      interactions was investigated using stable isotope labelling by amino acids in
      cell culture (SILAC)-based proteomics. We found that platelets promoted p38MAPK
      phosphorylation and MMP-9 up-regulation in both cell lines, with the subsequent
      cell-invasion-promoting effects. Pharmacological inhibition of p38MAPK led to a
      significant down-regulation of MMP-9 and colon cancer cell invasiveness. Also,
      p38MAPK-small interfering RNA abolished the induction of platelet-stimulated MMP
      9. SILAC experiments demonstrated that thrombospondin 1 (TSP1) was released
      mainly from platelets and clusterin by both platelets and cancer cells. Finally,
      inhibition of TSP1 and clusterin abolished p38MAPK phosphorylation, MMP-9
      activity and platelet-stimulated colon cancer invasion. Our results indicate that
      platelet-secreted TSP1 and clusterin promote the signal regulation of MMP-9 in
      platelet-induced colonic cancer invasion via a P38MAPK-regulated pathway. These
      findings are relevant to the development of therapeutic approaches to preventing
      and reducing tumour cell metastasis induced by colon adenocarcinoma. 

PMID- 24085799
TI  - miR-720 inhibits tumor invasion and migration in breast cancer by targeting
      TWIST1.
AB  - Breast cancer is the leading cause of cancer death among females, with tumor
      metastasis being primarily responsible for breast cancer-associated mortality.
      Current literatures have shown that microRNAs (miRNAs) are implicated in tumor
      metastasis. In this study, we found that the expression of miR-720 was
      significantly downregulated in primary breast cancer, with greater downregulation
      in metastatic tumors. Statistical analysis of 105 cases of primary human breast
      cancer demonstrated that decreased expression of miR-720 was correlated with
      lymph node metastasis. Furthermore, reexpression of miR-720 in breast cancer
      cells remarkably inhibited cell invasiveness and migration both in vitro and in
      vivo. Mechanistically, downregulation of TWIST1, a promoter of metastasis that
      was identified as a direct functional target of miR-720, was attributed to the
      inhibition of metastasis. Consistent with the reduced TWIST1 levels in breast
      cancer, reexpression of miR-720 upregulated epithelial markers (E-cadherin and
      beta-catenin) and downregulated mesenchymal markers (N-cadherin, fibronectin,
      vimentin and matrix metalloproteinase-2). Expression of miR-720 was inversely
      associated with TWIST1 in human breast cancer tissues. Knockdown of TWIST1
      expression by small interfering RNA exhibited similar effects to reintroduction
      of miR-720, whereas overexpression of TWIST1 (without the 3'-untranslated region)
      abrogated miR-720-mediated metastasis inhibition. Collectively, our data indicate
      that miR-720 is frequently decreased in breast cancer and manifests
      antimetastatic activity by downregulating TWIST1, presenting a novel mechanism of
      miRNA-mediated regulation of tumor metastasis. 

PMID- 24085800
TI  - SDF-1/CXCR4 axis promotes directional migration of colorectal cancer cells
      through upregulation of integrin alphavbeta6.
AB  - Colorectal cancer (CRC) displays a predilection for metastasis to liver. Although
      stromal cell-derived factor-1 (SDF-1)/CXCR4 plays an important role in the liver
      metastasis, the molecular mechanism still remains obscure. We previously reported
      that integrin alphavbeta6 was implicated in the progression of CRC. However, no
      data are currently available on the cross talk between CXCR4 and alphavbeta6. In
      the present study, we first demonstrated the cross talk between CXCR4 and
      alphavbeta6 and their role in liver metastasis of CRC. We analyzed 159 human CRC
      samples and found that expression of CXCR4 and alphavbeta6 was significantly
      associated with liver metastasis, and interestingly expression of alphavbeta6
      significantly correlated with expression of CXCR4. Both CXCR4 and alphavbeta6
      were highly expressed in metastatic CRC cell lines HT-29 and WiDr, whereas both
      of them were exiguous in non-metastatic cell line Caco-2. Furthermore, inhibition
      of alphavbeta6 significantly decreased SDF-1alpha-induced cell migration in
      vitro. SDF-1/CXCR4 could upregulate alphavbeta6 expression through
      phosphorylation of ERK and activation of Ets-1 transcription factor. In
      conclusion, we demonstrate that SDF-1/CXCR4 induces directional migration and
      liver metastasis of CRC cells by upregulating alphavbeta6 through ERK/Ets-1
      pathway. These data support combined inhibition of CXCR4 and alphavbeta6 to
      prevent development of liver metastasis of CRC. 

PMID- 24085802
TI  - An uncommon syndrome makes us reflect on our approach to diagnosis.

PMID- 24085801
TI  - Exogenous gibberellins induce wheat spike development under short days only in
      the presence of VERNALIZATION1.
AB  - The activation of the meristem identity gene VERNALIZATION1 (VRN1) is a critical
      regulatory point in wheat (Triticum spp.) flowering. In photoperiod-sensitive
      wheat varieties, VRN1 is expressed only under long days (LDs), but mutants
      carrying deletions in a regulatory element in its promoter show VRN1
      transcription and early spike development under short days (SDs). However,
      complete spike development is delayed until plants are transferred to LDs,
      indicating the existence of an additional regulatory mechanism dependent on LDs.
      We show here that exogenous gibberellin (GA) application accelerates spike
      development under SDs, but only in wheat lines expressing VRN1. The simultaneous
      presence of GA and VRN1 results in the up-regulation of the floral meristem
      identity genes SUPPRESSOR OF OVEREXPRESSION OF CONSTANS1-1 and LEAFY, whereas
      inhibition of GA biosynthesis with paclobutrazol precludes the LD induction of
      these two genes. The inductive role of GA on wheat flowering is further supported
      by the up-regulation of GA biosynthetic genes in the apices of plants transferred
      from SDs to LDs and in photoperiod-insensitive and transgenic wheat plants with
      increased FLOWERING LOCUS T transcription under SDs. The up-regulation of GA
      biosynthetic genes was not observed in the leaves of the same genetic stocks.
      Based on these observations, we propose a model in which FLOWERING LOCUS T is up
      regulated in the leaves under LDs and is then transported to the shoot apical
      meristem, where it simultaneously induces the expression of VRN1 and GA
      biosynthetic genes, which are both required for the up-regulation of the early
      floral meristem genes SUPPRESSOR OF OVEREXPRESSION OF CONSTANS1-1 and LEAFY and
      the timely development of the wheat spike. 

PMID- 24085803
TI  - Q: is anticoagulation appropriate for all patients with portal vein thrombosis?

PMID- 24085804
TI  - The overdiagnosis of pneumonia.

PMID- 24085805
TI  - Another perspective: reducing the overtreatment of pneumonia.

PMID- 24085806
TI  - Peripheral opacity on plain chest radiography.

PMID- 24085807
TI  - A practical approach to prescribing antidepressants.
AB  - Although antidepressant drugs do not differ much in their efficacy rates, the
      particular characteristics of one drug may make it a better choice in a given
      patient. This article provides insight into the art of prescribing
      antidepressants in primary care, with recommendations for prescribing for
      patients with chronic pain, sexual dysfunction, anxiety, chronic fatigue
      syndrome, fibromyalgia, severe insomnia, old age, diabetes, and heart problems. 

PMID- 24085808
TI  - More than skin-deep.

PMID- 24085809
TI  - The jugular venous pressure revisited.
AB  - Assessment of the jugular venous pressure is often inadequately performed and
      undervalued. Here, we review the physiologic and anatomic basis for the jugular
      venous pressure, including the discrepancy between right atrial and central
      venous pressures. We also describe the correct method of evaluating this clinical
      finding and review the clinical relevance of the jugular venous pressure,
      especially its value in assessing the severity and response to treatment of
      congestive heart failure. Waveforms reflective of specific conditions are also
      discussed. 

PMID- 24085810
TI  - Hepatocellular carcinoma: options for diagnosing and managing a deadly disease.
AB  - Hepatocellular carcinoma (HCC) is an important cause of death in patients with
      liver disease, and its incidence appears to be rising in the United States.
      Because early diagnosis improves the chances of survival, it is important to
      identify patients who would benefit from surveillance. Once HCC is suspected on
      surveillance, noninvasive diagnostic tests are available to make an accurate
      diagnosis. Treatment should be individualized, based on the characteristics of
      the tumor and the degree of liver dysfunction. 

PMID- 24085811
TI  - Antisynthetase syndrome: not just an inflammatory myopathy.
AB  - In recent years, antisynthetase syndrome has been recognized as an important
      cause of autoimmune inflammatory myopathy in a subset of patients with
      polymyositis and dermatomyositis. It is associated with serum antibodies to
      aminoacyl-transfer RNA synthetases and is characterized by a constellation of
      manifestations, including fever, myositis, interstitial lung disease, "mechanic's
      hands," Raynaud phenomenon, and polyarthritis. Physicians should be familiar with
      its variety of clinical presentations and should include it in the differential
      diagnosis in patients presenting with unexplained interstitial lung disease. 

PMID- 24085814
TI  - Comment on "midterm results and complications after minimally invasive distal
      metatarsal osteotomy for treatment of hallux valgus".

PMID- 24085815
TI  - Author response.

PMID- 24085812
TI  - Integrated glycoproteomics demonstrates fucosylated serum paraoxonase 1
      alterations in small cell lung cancer.
AB  - Small cell lung cancer (SCLC) is an aggressive type of lung cancer, and the
      detection of SCLCs at an early stage is necessary for successful therapy and for
      improving cancer survival rates. Fucosylation is one of the most common
      glycosylation-based modifications. Increased levels of fucosylation have been
      reported in a number of pathological conditions, including cancers. In this
      study, we aimed to identify and validate the aberrant and selective fucosylated
      glycoproteins in the sera of patients with SCLC. Fucosylated glycoproteins were
      enriched by the Aleuria aurantia lectin column after serum albumin and IgG
      depletion. In a narrowed down and comparative data analysis of both label-free
      proteomics and isobaric peptide-tagging chemistry iTRAQ approaches, the
      fucosylated glycoproteins were identified as up- or down-regulated in the sera of
      limited disease and extensive disease stage patients with SCLC. Verification was
      performed by multiple reaction monitoring-mass spectrometry to select reliable
      markers. Four fucosylated proteins, APCS, C9, SERPINA4, and PON1, were selected
      and subsequently validated by hybrid A. aurantia lectin ELISA (HLE) and Western
      blotting. Compared with Western blotting, the HLE analysis of these four proteins
      produced more optimal diagnostic values for SCLC. The PON1 protein levels were
      significantly reduced in the sera of patients with SCLC, whereas the fucosylation
      levels of PON1 were significantly increased. Fucosylated PON1 exhibited an area
      under curve of 0.91 for the extensive disease stage by HLE, whereas the PON1
      protein levels produced an area under curve of 0.82 by Western blot. The glycan
      structural analysis of PON1 by MS/MS identified a biantennary fucosylated glycan
      modification consisting of a core + 2HexNAc + 1Fuc at increased levels in the
      sera of patients with SCLC. In addition, the PON1 levels were decreased in the
      sera of the Lewis lung carcinoma lung cancer mouse model that we examined. Our
      data suggest that fucosylated protein biomarkers, such as PON1, and their
      fucosylation levels and patterns can serve as diagnostic and prognostic
      serological markers for SCLC. 

PMID- 24085817
TI  - Emergence of carbapenem-resistant Acinetobacter baumannii in hospitals in
      Pakistan.
AB  - The emergence of pan-resistance in bacterial pathogens poses a threat to human
      health. Carbapenem-resistant Acinetobacter baumannii has emerged as a serious
      challenge, causing nosocomial infection and community-acquired outbreaks in
      hospitals globally, including in Pakistan. We collected 90 Acinetobacter isolates
      from patients with secondary or nosocomial infections from different hospitals in
      Pakistan and screened for carbapenem-resistant strains. Of the 90 isolates, 59
      were resistant to carbapenems. Among oxacillinase -encoding genes, blaOXA-51-like
      was common in all isolates, including in combination with blaOXA-23-like in 14
      isolates; however, blaOXA-24-like and blaOXA-58-like were completely absent.
      Among metallo-beta-lactamase-encoding genes, only blaNDM-1 was found in one
      isolate, while the other three genes, blaIMP, blaVIM and blaSIM, were completely
      absent. None of the isolates was found to harbour the blaCTX-M gene. The isolates
      were also tested for susceptibilities to a panel of different antibiotics
      belonging to several classes. Of all the drugs tested, tigecycline was the most
      effective with 80 % sensitivity amongst isolates, followed by colistin with 50 %
      sensitivity. Three categories of resistance were found in these isolates: extreme
      drug resistance in 26, pan-drug resistance in 19 and multidrug resistance in 87
      isolates. The isolates exhibited a high resistance to cephalosporins,
      trimethoprim-sulfamethoxazole and beta-lactam antibiotics, followed by
      tetracycline and beta-lactam/beta-lactam inhibitor combination, fluoroquinolone
      and aminoglycosides. The results show a prominent level of antibiotic-resistance
      phenotypes in A. baumannii and strongly suggest the need for full-scale national
      surveillance of carbapenem-resistant A. baumannii with particular emphasis on the
      newly identified NDM-1 (New Delhi metallo-beta-lactamase-1).

PMID- 24085818
TI  - Giardia duodenalis typing from stools: a comparison of three approaches to
      extracting DNA, and validation of a probe-based real-time PCR typing assay.
AB  - A weighted, multi-attribute approach was used to compare three methods for direct
      extraction of Giardia duodenalis DNA from 15 microscopy-positive stools: (1) a
      QIAamp spin-column method for stools including a 10 min incubation at 95  degrees
      C, (2) method 1 preceded by five freeze-thaw cycles and (3) bead beating with
      guanidine thiocyanate using a FastPrep-28 machine followed by liquid-phase silica
      purification of DNA. The attributes compared included DNA yield measured using a
      new triose phosphate isomerase (tpi) gene probe-based real-time PCR, also
      described here. All three methods shared 100 % PCR positivity, while the bead
      beating method provided the highest G. duodenalis DNA yield (P<0.01). However,
      when other weighted attributes, including biocontainment, resources and technical
      requirements, were also considered, spin-column extraction with prior freeze-thaw
      treatment (method 2) was deemed the most desirable and was selected for use. The
      tpi real-time PCR typing assay was designed to discriminate between the main
      human infectious assemblages of G. duodenalis (A and B) and was evaluated
      initially using standard isolates. Validation using microscopy-positive stools
      from 78 clinical giardiasis cases revealed 100 % typability; 20 (26 %) samples
      contained assemblage A, 56 (72 %) assemblage B and two (3 %) assemblages A and B.
      While the epidemiological significance of assemblage distribution will be
      revealed as more isolates are typed and analysed with patient demographic and
      exposure data, the utility of this assay and its ready application in our
      laboratory workflow and result turnaround margins is already evident.

PMID- 24085819
TI  - Melanocortin 4 receptor becomes an ACTH receptor by coexpression of melanocortin
      receptor accessory protein 2.
AB  - Melanocortin 2 receptor (MC2R) is the only canonical ACTH receptor. Its
      functional expression requires the presence of an accessory protein, known as
      melanocortin receptor 2 accessory protein 1 (MRAP1). The vertebrate genome
      exhibits a paralogue gene called MRAP2, which is duplicated in zebrafish (MRAP2a
      and MRAP2b), although its function remains unknown. In this paper, we demonstrate
      that MRAP2a enables MC4R, a canonical MSH receptor, to be activated by ACTH with
      a similar sensitivity to that exhibited by MC2R. Both proteins physically
      interact and are coexpressed in the neurons of the preoptic area, a key region in
      the control of the energy balance and hypophyseal secretion in fish. ACTH
      injections inhibit food intake in wild-type zebrafish but not in fish lacking
      functional MC4R. Both MRAP1 and MRAP2a are hormonally regulated, suggesting that
      these proteins are substrates for feed-back regulatory pathways of melanocortin
      signaling. Fasting has no effect on the central expression of MRAP2a but
      stimulates MRAP2b expression. This protein interacts and is colocalized with MC4R
      in the tuberal hypothalamic neurons but has no effect on the pharmacologic
      profile of MC4R. However, MRPA2b is able to decrease basal reporter activity in
      cell lines expressing MC4R. It is plausible that MRAP2b decreases the
      constitutive activity of the MC4R during fasting periods, driving the animal
      toward a positive energy balance. Our data indicate that MRAP2s control the
      activity of MC4R, opening up new pathways for the regulation of melanocortin
      signaling and, by extension, for the regulation of the energy balance and
      obesity. 

PMID- 24085820
TI  - Female-specific induction of rat pituitary dentin matrix protein-1 by GnRH.
AB  - Hypothalamic GnRH is the primary regulator of reproduction in vertebrates, acting
      via the G protein-coupled GnRH receptor (GnRHR) in pituitary gonadotrophs to
      control synthesis and release of gonadotropins. To identify elements of the GnRHR
      coupled gene network, GnRH was applied in a pulsatile manner for 6 hours to a
      mixed population of perifused pituitary cells from cycling females, mRNA was
      extracted, and RNA sequencing analysis was performed. This revealed 83 candidate
      regulated genes, including a large number coding for secreted proteins. Most
      notably, GnRH induces a greater than 600-fold increase in expression of dentin
      matrix protein-1 (Dmp1), one of five members of the small integrin-binding ligand
      N-linked glycoprotein gene family. The Dmp1 response is mediated by the GnRHR,
      not elicited by other hypothalamic releasing factors, and is approximately 20
      fold smaller in adult male pituitary cells. The sex-dependent Dmp1 response is
      established during the peripubertal period and independent of the developmental
      pattern of Gnrhr expression. In vitro, GnRH-induced expression of this gene is
      coupled with release of DMP1 in extracellular medium through the regulated
      secretory pathway. In vivo, pituitary Dmp1 expression in identified gonadotrophs
      is elevated after ovulation. Cell signaling studies revealed that the GnRH
      induction of Dmp1 is mediated by the protein kinase C signaling pathway and
      reflects opposing roles of ERK1/2 and p38 MAPK; in addition, the response is
      facilitated by progesterone. These results establish that DMP1 is a novel
      secretory protein of female rat gonadotrophs, the synthesis and release of which
      are controlled by the hypothalamus through the GnRHR signaling pathway. This
      advance raises intriguing questions about the intrapituitary and downstream
      effects of this new player in GnRH signaling. 

PMID- 24085821
TI  - Prostate androgen-regulated mucin-like protein 1: a novel regulator of
      progesterone metabolism.
AB  - The LH surge reprograms preovulatory follicular cells to become terminally
      differentiated luteal cells which produce high levels of progesterone and become
      resistant to apoptosis. PARM1 (prostate androgen regulated mucin-like protein 1)
      has been implicated in cell differentiation and cell survival in nonovarian
      cells, but little is known about PARM1 in the ovary. This study demonstrated that
      the LH surge induced a dramatic increase in Parm1 expression in periovulatory
      follicles and newly forming CL in both cycling and immature rat models. We
      further demonstrated that hCG increases Parm1 expression in granulosa cell
      cultures. The in vitro up-regulation of Parm1 expression was mediated by hCG
      activated multiple signaling pathways and transcriptional activation of this
      gene. Parm1 knockdown increased the viability of cultured granulosa cells but
      resulted in a decrease in progesterone levels. The inhibitory effect of Parm1
      silencing on progesterone was reversed by adenoviral mediated add-back expression
      of Parm1. Parm1 silencing had little effect on the expression of genes involved
      in progesterone biosynthesis and metabolism such as Scarb1, Ldlr, Vldlr, Scp2,
      Star, Cyp11a1, Hsd3b, and Srd5a1, while decreasing the expression of Akr1c3.
      Analyses of culture media steroid levels revealed that Parm1 knockdown had no
      effect on pregnenolone levels, while resulting in time-dependent decreases in
      progesterone and 20alpha-dihydroprogesterone and accelerated accumulation of
      5alpha-pregnanediol. This study revealed that the up-regulation of Parm1
      expression promotes progesterone and 20alpha-dihydroprogesterone accumulation in
      luteinizing granulosa cells by inhibiting progesterone catabolism to 5alpha
      pregnanediol. PARM1 contributes to ovulation and/or luteal function by acting as
      a novel regulator of progesterone metabolism. 

PMID- 24085824
TI  - Trauma, tragedy, and heartfelt thanks.

PMID- 24085822
TI  - Gonadotropin-releasing hormone-regulated prohibitin mediates apoptosis of the
      gonadotrope cells.
AB  - GnRH regulates circulating levels of the gonadotropins but has also been
      implicated in establishing the gonadotrope cell population. Consistent with this,
      GnRH induces proliferation of partially differentiated gonadotropes, while
      reducing the numbers of fully differentiated cells. We have previously reported
      that the proapoptotic protein, prohibitin (PHB) is expressed more abundantly in
      gonadotrope-derived LbetaT2 cells than in partially differentiated alphaT3-1
      gonadotrope precursor cells, suggesting a possible role for PHB in GnRH-induced
      apoptosis. We show here that PHB is required for GnRH-induced apoptosis in mature
      gonadotropes. PHB expression and activity are regulated by GnRH: its
      transcription is via c-Jun NH2-terminal kinase, whereas its nuclear export
      follows activation of ERK. Moreover, PHB levels are down-regulated by microRNA27,
      which is expressed at lower levels in mature gonadotropes, possibly explaining
      the switch to an apoptotic response with development. PHB is required for
      mitochondrial import of the proapoptotic BAX, whose expression is also induced by
      GnRH-activated c-Jun NH2-terminal kinase, as is expression of the BH3-only
      protein, HRK, and this too plays a role in GnRH-induced apoptosis. Finally, we
      show that gonadotrope-specific PHB-knockout mice display reproductive
      abnormalities, including a larger gonadotrope population, increased LH levels,
      reduced fertility, and altered gonad development. We thus demonstrate a role for
      PHB in GnRH-induced cell death in mature gonadotropes, which is crucial for the
      normal development and function of the reproductive axis. 

PMID- 24085825
TI  - Tracheostomy care and complications in the intensive care unit.
AB  - Tracheotomy is a common procedure in intensive care units, and nurses must
      provide proper care to tracheostomy patients to prevent complications. One of the
      most important considerations is effective mobilization of secretions, and a
      suction catheter is the most important tool for that purpose. Each bedside should
      be equipped with a functional suctioning system, an oxygen source, a manual
      resuscitation bag, and a complete tracheostomy kit, which should accompany
      patients wherever they go in the hospital. Complications include infection,
      tracheomalacia, skin breakdown, and tracheoesophageal fistula. Tracheostomy
      emergencies include hemorrhage, tube dislodgement and loss of airway, and tube
      obstruction; such emergencies are managed more effectively when all necessary
      supplies are readily available at the bedside. This article describes how to
      provide proper care in the intensive care unit, strategies for preventing
      complications, and management of tracheostomy emergencies. 

PMID- 24085826
TI  - Safety recommendations for administering intravenous prostacyclins in the
      hospital.
AB  - Prostacyclins are a high-risk category of continuous intravenous infusions
      increasingly used in hospitals to treat advanced pulmonary arterial hypertension,
      a rare condition characterized by vasoconstriction and vascular proliferation of
      the pulmonary arteries. Prostacyclins are given in doses of nanograms per
      kilogram per minute and have a narrow therapeutic dosing range for each patient.
      Sudden increases or decreases in dose can be life threatening. Previous studies
      revealed errors in the administration of these high-risk infusions, which in some
      instances led to serious adverse events, including death. The literature was
      reviewed for safety measures in administration of high-risk intravenous
      medications and input was obtained from leading experts in pulmonary arterial
      hypertension to create a set of safety recommendations for infusion of
      prostacyclins. 

PMID- 24085827
TI  - From door to recovery: a collaborative approach to the development of a post
      cardiac arrest center.
AB  - Out-of-hospital cardiac arrest remains common and, despite advances in
      resuscitation practices, continues to carry a high mortality that may be
      influenced by several factors, including where a patient is cared for after the
      cardiac arrest. Implementing a post-cardiac arrest care guideline for survivors
      of out-of-hospital and in-hospital cardiac arrest involves a multidisciplinary
      approach with short-term and long-term strategies. Physician and nursing leaders
      must work in synergy to guide the implementation of an evidence-based plan of
      care. A collaborative approach was used at a hospital to develop processes, build
      consensus for protocols, and provide support to staff and teams. A joint approach
      has allowed the hospital to move from traditional silos of individual
      departmental care to a continuum of patient-focused management after cardiac
      arrest. This care coordination is initiated in the emergency department and
      follows the patient through to discharge. 

PMID- 24085828
TI  - Improving family satisfaction and participation in decision making in an
      intensive care unit.
AB  - Background Survey data revealed that families of patients in a surgical intensive
      care unit were not satisfied with their participation in decision making or with
      how well the multidisciplinary team worked together. Objectives To develop and
      implement an evidence-based communication algorithm and evaluate its effect in
      improving satisfaction among patients' families. Methods A multidisciplinary team
      developed an algorithm that included bundles of communication interventions at
      24, 72, and 96 hours after admission to the unit. The algorithm included clinical
      triggers, which if present escalated the algorithm. A pre-post design using
      process improvement methods was used to compare families' satisfaction scores
      before and after implementation of the algorithm. Results Satisfaction scores for
      participation in decision making (45% vs 68%; z = -2.62, P = .009) and how well
      the health care team worked together (64% vs 83%; z = -2.10, P = .04) improved
      significantly after implementation. Conclusions Use of an evidence-based
      structured communication algorithm may be a way to improve satisfaction of
      families of intensive care patients with their participation in decision making
      and their perception of how well the unit's team works together. 

PMID- 24085829
TI  - The goddess of wisdom.

PMID- 24085830
TI  - Replacing gastrostomy tubes.

PMID- 24085831
TI  - Maintaining patients' privacy and confidentiality with family communications in
      the intensive care unit.

PMID- 24085833
TI  - Alarm management.

PMID- 24085834
TI  - I am a critical care nurse.

PMID- 24085835
TI  - Silencing and activating type IV secretion genes of the F-like conjugative
      resistance plasmid R1.
AB  - Expression of DNA transfer (tra) genes of F-type conjugative plasmids is required
      for the assembly of a functional type IV secretion machinery and subsequent
      plasmid DNA transfer from donor to recipient cells. Transcription of tra genes
      depends on the activation of a single promoter, designated PY, by the plasmid
      encoded TraJ protein. We here determine plasmid specificity of TraJ proteins from
      various subgroups of F-like plasmids and find that plasmid R1 conjugation and PY
      promoter activation can be achieved only by its cognate activator and by TraJ of
      the Salmonella plasmid pSLT and not by F or R100 TraJ proteins. In addition, we
      characterize the PY promoter of plasmid R1. We show that TraJ binds to PY DNA in
      vivo and that H-NS acts as a silencer of the PY promoter. In the natural plasmid
      context, H-NS silences transfer gene expression and horizontal plasmid DNA
      transfer. In contrast to what was found for the F plasmid, lack of H-NS did not
      abolish the requirement for ArcA and TraJ to reach full tra gene expression and
      DNA transfer activity. We propose that, besides a passive de-silencing activity,
      both ArcA and TraJ play a direct role in synergistically stimulating tra operon
      transcription and subsequent DNA transfer. 

PMID- 24085836
TI  - Membrane-bound oxygen reductases of the anaerobic sulfate-reducing Desulfovibrio
      vulgaris Hildenborough: roles in oxygen defence and electron link with
      periplasmic hydrogen oxidation.
AB  - Cytoplasmic membranes of the strictly anaerobic sulfate-reducing bacterium
      Desulfovibrio vulgaris Hildenborough contain two terminal oxygen reductases, a bd
      quinol oxidase and a cc(b/o)o3 cytochrome oxidase (Cox). Viability assays pointed
      out that single Deltabd, Deltacox and double DeltabdDeltacox deletion mutant
      strains were more sensitive to oxygen exposure than the WT strain, showing the
      involvement of these oxygen reductases in the detoxification of oxygen. The
      Deltacox strain was slightly more sensitive than the Deltabd strain, pointing to
      the importance of the cc(b/o)o3 cytochrome oxidase in oxygen protection.
      Decreased O2 reduction rates were measured in mutant cells and membranes using
      lactate, NADH, ubiquinol and menadiol as substrates. The affinity for oxygen
      measured with the bd quinol oxidase (Km, 300 nM) was higher than that of the
      cc(b/o)o3 cytochrome oxidase (Km, 620 nM). The total membrane activity of the bd
      quinol oxidase was higher than that of the cytochrome oxidase activity in line
      with the higher expression of the bd oxidase genes. In addition, analysis of the
      DeltabdDeltacox mutant strain indicated the presence of at least one O2
      scavenging membrane-bound system able to reduce O2 with menaquinol as electron
      donor with an O2 affinity that was two orders of magnitude lower than that of the
      bd quinol oxidase. The lower O2 reductase activity in mutant cells with hydrogen
      as electron donor and the use of specific inhibitors indicated an electron
      transfer link between periplasmic H2 oxidation and membrane-bound oxygen
      reduction via the menaquinol pool. This linkage is crucial in defence of the
      strictly anaerobic bacterium Desulfovibrio against oxygen stress. 

PMID- 24085837
TI  - Kinetic modelling of the Zymomonas mobilis Entner-Doudoroff pathway: insights
      into control and functionality.
AB  - Zymomonas mobilis, an ethanol-producing bacterium, possesses the Entner-Doudoroff
      (E-D) pathway, pyruvate decarboxylase and two alcohol dehydrogenase isoenzymes
      for the fermentative production of ethanol and carbon dioxide from glucose. Using
      available kinetic parameters, we have developed a kinetic model that incorporates
      the enzymic reactions of the E-D pathway, both alcohol dehydrogenases, transport
      reactions and reactions related to ATP metabolism. After optimizing the reaction
      parameters within likely physiological limits, the resulting kinetic model was
      capable of simulating glycolysis in vivo and in cell-free extracts with good
      agreement with the fluxes and steady-state intermediate concentrations reported
      in previous experimental studies. In addition, the model is shown to be
      consistent with experimental results for the coupled response of ATP
      concentration and glycolytic flux to ATPase inhibition. Metabolic control
      analysis of the model revealed that the majority of flux control resides not
      inside, but outside the E-D pathway itself, predominantly in ATP consumption,
      demonstrating why past attempts to increase the glycolytic flux through
      overexpression of glycolytic enzymes have been unsuccessful. Co-response analysis
      indicates how homeostasis of ATP concentrations starts to deteriorate markedly at
      the highest glycolytic rates. This kinetic model has potential for application in
      Z. mobilis metabolic engineering and, since there are currently no E-D pathway
      models available in public databases, it can serve as a basis for the development
      of models for other micro-organisms possessing this type of glycolytic pathway. 

PMID- 24085838
TI  - The Geobacillus paradox: why is a thermophilic bacterial genus so prevalent on a
      mesophilic planet?
AB  - The genus Geobacillus comprises endospore-forming obligate thermophiles. These
      bacteria have been isolated from cool soils and even cold ocean sediments in
      anomalously high numbers, given that the ambient temperatures are significantly
      below their minimum requirement for growth. Geobacilli are active in environments
      such as hot plant composts, however, and examination of their genome sequences
      reveals that they are endowed with a battery of sensors, transporters and enzymes
      dedicated to hydrolysing plant polysaccharides. Although they appear to be
      relatively minor members of the plant biomass-degrading microbial community,
      Geobacillus bacteria have achieved a significant population with a worldwide
      distribution, probably in large part due to adaptive features of their spores.
      First, their morphology and resistance properties enable them to be mobilized in
      the atmosphere and transported long distances. Second, their longevity, which in
      theory may be extreme, enables them to lie quiescent but viable for long periods
      of time, accumulating gradually over time to achieve surprisingly high population
      densities. 

PMID- 24085839
TI  - Using an epidemiological model for phylogenetic inference reveals density
      dependence in HIV transmission.
AB  - The control, prediction, and understanding of epidemiological processes require
      insight into how infectious pathogens transmit in a population. The chain of
      transmission can in principle be reconstructed with phylogenetic methods which
      analyze the evolutionary history using pathogen sequence data. The quality of the
      reconstruction, however, crucially depends on the underlying epidemiological
      model used in phylogenetic inference. Until now, only simple epidemiological
      models have been used, which make limiting assumptions such as constant rate
      parameters, infinite total population size, or deterministically changing
      population size of infected individuals. Here, we present a novel phylogenetic
      method to infer parameters based on a classical stochastic epidemiological model.
      Specifically, we use the susceptible-infected-susceptible model, which accounts
      for density-dependent transmission rates and finite total population size,
      leading to a stochastically changing infected population size. We first validate
      our method by estimating epidemic parameters for simulated data and then apply it
      to transmission clusters from the Swiss HIV epidemic. Our estimates of the basic
      reproductive number R0 for the considered Swiss HIV transmission clusters are
      significantly higher than previous estimates, which were derived assuming
      infinite population size. This difference in key parameter estimates highlights
      the importance of careful model choice when doing phylogenetic inference. In
      summary, this article presents the first fully stochastic implementation of a
      classical epidemiological model for phylogenetic inference and thereby addresses
      a key aspect in ongoing efforts to merge phylogenetics and epidemiology. 

PMID- 24085840
TI  - Cellular uptake of the antitumor agent Dp44mT occurs via a carrier/receptor
      mediated mechanism.
AB  - The chelator di-2-pyridylketone 4,4-dimethyl-3-thiosemicarbazone (Dp44mT) shows
      potent and selective anticancer and antimetastatic activity. However, the
      mechanism by which it is initially transported into cells to induce cytotoxicity
      is unknown. Hence, the current investigation examined the cellular uptake of 14C
      Dp44mT relative to two structurally related ligands, namely the aroylhydrazone
      14C-pyridoxal isonicotinoyl hydrazone (14C-PIH) and the thiosemicarbazone (14C-2
      benzoylpyridine 4-ethyl-3-thiosemicarbazone (14C-Bp4eT). In marked contrast to
      the cellular uptake of 14C-PIH and 14C-Bp4eT, which were linear as a function of
      concentration, 14C-Dp44mT uptake was saturable using SK-N-MC neuroepithelioma
      cells (Bmax, 4.28 * 107 molecules of chelator/cell; and Kd, 2.45 MUM). Together
      with the fact that 14C-Dp44mT uptake was temperature-dependent and significantly
      (P < 0.01) decreased by competing unlabeled Dp44mT, these observations indicated
      a saturable transport mechanism consistent with carrier/receptor-mediated
      transport. Other unlabeled ligands that shared the saturated N4 structural moiety
      with Dp44mT significantly (P < 0.01) inhibited 14C-Dp44mT uptake, illustrating
      its importance for carrier/receptor recognition. Nevertheless, unlabeled Dp44mT
      most markedly decreased (14C-Dp44mT uptake, demonstrating that the putative
      carrier/receptor shows high selectivity for Dp44mT. Interestingly, in contrast to
      14C-Dp44mT, uptake of its Fe complex [Fe(14C-Dp44mT)2] was not saturable as a
      function of concentration and was much greater than the ligand alone, indicating
      an alternate mode of transport. Studies examining the tissue distribution of 14C
      Dp44mT injected intravenously into a mouse tumor model demonstrated the 14C label
      was primarily identified in the excretory system. Collectively, these findings
      examining the mechanism of Dp44mT uptake and its distribution and excretion have
      clinical implications for its bioavailability and uptake in vivo.

PMID- 24085841
TI  - Increase in cellular cyclic AMP concentrations reverses the profibrogenic
      phenotype of cardiac myofibroblasts: a novel therapeutic approach for cardiac
      fibrosis.
AB  - Tissue fibrosis is characterized by excessive production, deposition, and
      contraction of the extracellular matrix (ECM). The second messenger cAMP has
      antifibrotic effects in fibroblasts from several tissues, including cardiac
      fibroblasts (CFs). Increased cellular cAMP levels can prevent the transformation
      of CFs into profibrogenic myofibroblasts, a critical step that precedes increased
      ECM deposition and tissue fibrosis. Here we tested two hypotheses: 1)
      myofibroblasts have a decreased ability to accumulate cAMP in response to G
      protein-coupled receptor (GPCR) agonists, and 2) increasing cAMP will not only
      prevent, but also reverse, the myofibroblast phenotype. We found that
      myofibroblasts produce less cAMP in response to GPCR agonists or forskolin and
      have decreased expression of several adenylyl cyclase (AC) isoforms and increased
      expression of multiple cyclic nucleotide phosphodiesterases (PDEs). Furthermore,
      we found that forskolin-promoted increases in cAMP or N(6)-phenyladenosine-cAMP,
      a protein kinase A-selective analog, reverse the myofibroblast phenotype, as
      assessed by the expression of collagen Ialpha1, alpha-smooth muscle actin,
      plasminogen activator inhibitor-1, and cellular contractile abilities, all
      hallmarks of a fibrogenic state. These results indicate that: 1) altered
      expression of AC and PDE isoforms yield a decrease in cAMP concentrations of
      cardiac myofibroblasts (relative to CFs) that likely contributes to their
      profibrotic state, and 2) approaches to increase cAMP concentrations not only
      prevent fibroblast-to-myofibroblast transformation but also can reverse the
      profibrotic myofibroblastic phenotype. We conclude that therapeutic strategies
      designed to enhance cellular cAMP concentrations in CFs may provide a means to
      reverse excessive scar formation following injury and to treat cardiac fibrosis. 

PMID- 24085843
TI  - Insights into insect wing origin provided by functional analysis of vestigial in
      the red flour beetle, Tribolium castaneum.
AB  - Despite accumulating efforts to unveil the origin of insect wings, it remains one
      of the principal mysteries in evolution. Currently, there are two prominent
      models regarding insect wing origin: one connecting the origin to the paranotal
      lobe and the other to the proximodorsal leg branch (exite). However, neither
      hypothesis has been able to surpass the other. To approach this conundrum, we
      focused our analysis on vestigial (vg), a critical wing gene initially identified
      in Drosophila. Our investigation in Tribolium (Coleoptera) has revealed that,
      despite the well-accepted view of vg as an essential wing gene, there are two
      groups of vg-dependent tissues in the "wingless" first thoracic segment (T1). We
      show that one of these tissues, the carinated margin, also depends on other
      factors essential for wing development (such as Wingless signal and apterous),
      and has nubbin enhancer activity. In addition, our homeotic mutant analysis shows
      that wing transformation in T1 originates from both the carinated margin and the
      other vg-dependent tissue, the pleural structures (trochantin and epimeron).
      Intriguingly, these two tissues may actually be homologous to the two proposed
      wing origins (paranotal lobes and exite bearing proximal leg segments).
      Therefore, our findings suggest that the vg-dependent tissues in T1 could be wing
      serial homologs present in a more ancestral state, thus providing compelling
      functional evidence for the dual origin of insect wings. 

PMID- 24085844
TI  - Arf6 coordinates actin assembly through the WAVE complex, a mechanism usurped by
      Salmonella to invade host cells.
AB  - ADP ribosylation factor (Arf) 6 anchors to the plasma membrane, where it
      coordinates membrane trafficking and cytoskeleton remodelling, but how it
      assembles actin filaments is unknown. By reconstituting membrane-associated actin
      assembly mediated by the WASP family veroprolin homolog (WAVE) regulatory complex
      (WRC), we recapitulated an Arf6-driven actin polymerization pathway. We show that
      Arf6 is divergent from other Arf members, as it was incapable of directly
      recruiting WRC. We demonstrate that Arf6 triggers actin assembly at the membrane
      indirectly by recruiting the Arf guanine nucleotide exchange factor (GEF) ARNO
      that activates Arf1 to enable WRC-dependent actin assembly. The pathogen
      Salmonella usurped Arf6 for host cell invasion by recruiting its canonical GEFs
      EFA6 and BRAG2. Arf6 and its GEFs facilitated membrane ruffling and pathogen
      invasion via ARNO, and triggered actin assembly by generating an Arf1-WRC
      signaling hub at the membrane in vitro and in cells. This study reconstitutes
      Arf6-dependent actin assembly to reveal a mechanism by which related Arf GTPases
      orchestrate distinct steps in the WRC cytoskeleton remodelling pathway. 

PMID- 24085845
TI  - Stabilization of mutant BRCA1 protein confers PARP inhibitor and platinum
      resistance.
AB  - Breast Cancer Type 1 Susceptibility Protein (BRCA1)-deficient cells have
      compromised DNA repair and are sensitive to poly(ADP-ribose) polymerase (PARP)
      inhibitors. Despite initial responses, the development of resistance limits
      clinical efficacy. Mutations in the BRCA C-terminal (BRCT) domain of BRCA1
      frequently create protein products unable to fold that are subject to protease
      mediated degradation. Here, we show HSP90-mediated stabilization of a BRCT domain
      mutant BRCA1 protein under PARP inhibitor selection pressure. The stabilized
      mutant BRCA1 protein interacted with PALB2-BRCA2-RAD51, was essential for RAD51
      focus formation, and conferred PARP inhibitor as well as cisplatin resistance.
      Treatment of resistant cells with the HSP90 inhibitor 17-dimethylaminoethylamino
      17-demethoxygeldanamycin reduced mutant BRCA1 protein levels and restored their
      sensitivity to PARP inhibition. Resistant cells also acquired a TP53BP1 mutation
      that facilitated DNA end resection in the absence of a BRCA1 protein capable of
      binding CtIP. Finally, concomitant increased mutant BRCA1 and decreased 53BP1
      protein expression occur in clinical samples of BRCA1-mutated recurrent ovarian
      carcinomas that have developed resistance to platinum. These results provide
      evidence for a two-event mechanism by which BRCA1-mutant tumors acquire
      anticancer therapy resistance. 

PMID- 24085846
TI  - How allosteric control of Staphylococcus aureus penicillin binding protein 2a
      enables methicillin resistance and physiological function.
AB  - The expression of penicillin binding protein 2a (PBP2a) is the basis for the
      broad clinical resistance to the beta-lactam antibiotics by methicillin-resistant
      Staphylococcus aureus (MRSA). The high-molecular mass penicillin binding proteins
      of bacteria catalyze in separate domains the transglycosylase and transpeptidase
      activities required for the biosynthesis of the peptidoglycan polymer that
      comprises the bacterial cell wall. In bacteria susceptible to beta-lactam
      antibiotics, the transpeptidase activity of their penicillin binding proteins
      (PBPs) is lost as a result of irreversible acylation of an active site serine by
      the beta-lactam antibiotics. In contrast, the PBP2a of MRSA is resistant to beta
      lactam acylation and successfully catalyzes the DD-transpeptidation reaction
      necessary to complete the cell wall. The inability to contain MRSA infection with
      beta-lactam antibiotics is a continuing public health concern. We report herein
      the identification of an allosteric binding domain--a remarkable 60 A distant
      from the DD-transpeptidase active site--discovered by crystallographic analysis
      of a soluble construct of PBP2a. When this allosteric site is occupied, a
      multiresidue conformational change culminates in the opening of the active site
      to permit substrate entry. This same crystallographic analysis also reveals the
      identity of three allosteric ligands: muramic acid (a saccharide component of the
      peptidoglycan), the cell wall peptidoglycan, and ceftaroline, a recently approved
      anti-MRSA beta-lactam antibiotic. The ability of an anti-MRSA beta-lactam
      antibiotic to stimulate allosteric opening of the active site, thus predisposing
      PBP2a to inactivation by a second beta-lactam molecule, opens an unprecedented
      realm for beta-lactam antibiotic structure-based design.

PMID- 24085847
TI  - Intermediate closed state for glycine receptor function revealed by cysteine
      cross-linking.
AB  - Pentameric ligand-gated ion channels (pLGICs) mediate signal transmission by
      coupling the binding of extracellular ligands to the opening of their ion
      channel. Agonist binding elicits activation and desensitization of pLGICs,
      through several conformational states, that are, thus far, incompletely
      characterized at the structural level. We previously reported for GLIC, a
      prokaryotic pLGIC, that cross-linking of a pair of cysteines at both sides of the
      extracellular and transmembrane domain interface stabilizes a locally closed (LC)
      X-ray structure. Here, we introduced the homologous pair of cysteines on the
      human alpha1 glycine receptor. We show by electrophysiology that cysteine cross
      linking produces a gain-of-function phenotype characterized by concomitant
      constitutive openings, increased agonist potency, and equalization of efficacies
      of full and partial agonists. However, it also produces a reduction of maximal
      currents at saturating agonist concentrations without change of the unitary
      channel conductance, an effect reversed by the positive allosteric modulator
      propofol. The cross-linking thus favors a unique closed state distinct from the
      resting and longest-lived desensitized states. Fitting the data according to a
      three-state allosteric model suggests that it could correspond to a LC
      conformation. Its plausible assignment to a gating intermediate or a fast
      desensitized state is discussed. Overall, our data show that relative movement of
      two loops at the extracellular-transmembrane interface accompanies orthosteric
      agonist-mediated gating. 

PMID- 24085849
TI  - Receptive field focus of visual area V4 neurons determines responses to illusory
      surfaces.
AB  - Illusory figures demonstrate the visual system's ability to infer surfaces under
      conditions of fragmented sensory input. To investigate the role of midlevel
      visual area V4 in visual surface completion, we used multielectrode arrays to
      measure spiking responses to two types of visual stimuli: Kanizsa patterns that
      induce the perception of an illusory surface and physically similar control
      stimuli that do not. Neurons in V4 exhibited stronger and sometimes rhythmic
      spiking responses for the illusion-promoting configurations compared with
      controls. Moreover, this elevated response depended on the precise alignment of
      the neuron's peak visual field sensitivity (receptive field focus) with the
      illusory surface itself. Neurons whose receptive field focus was over adjacent
      inducing elements, less than 1.5 degrees  away, did not show response enhancement
      to the illusion. Neither receptive field sizes nor fixational eye movements could
      account for this effect, which was present in both single-unit signals and
      multiunit activity. These results suggest that the active perceptual completion
      of surfaces and shapes, which is a fundamental problem in natural visual
      experience, draws upon the selective enhancement of activity within a distinct
      subpopulation of neurons in cortical area V4. 

PMID- 24085850
TI  - Prostaglandin E2 deficiency causes a phenotype of aspirin sensitivity that
      depends on platelets and cysteinyl leukotrienes.
AB  - Aspirin-exacerbated respiratory disease (AERD) is characterized by asthma, tissue
      eosinophilia, overproduction of cysteinyl leukotrienes (cysLTs), and respiratory
      reactions to nonselective cyclooxygenase (COX) inhibitors. Ex vivo studies
      suggest that functional abnormalities of the COX-2/microsomal prostaglandin
      (PG)E2 synthase-1 system may underlie AERD. We demonstrate that microsomal PGE2
      synthase-1 null mice develop a remarkably AERD-like phenotype in a model of
      eosinophilic pulmonary inflammation. Lysine aspirin (Lys-ASA)-challenged PGE2
      synthase-1 null mice exhibit sustained increases in airway resistance, along with
      lung mast cell (MC) activation and cysLT overproduction. A stable PGE2 analog and
      a selective E prostanoid (EP)2 receptor agonist blocked the responses to Lys-ASA
      by ~90%; EP3 and EP4 agonists were also active. The increases in airway
      resistance and MC products were blocked by antagonists of the type 1 cysLT
      receptor or 5-lipoxygenase, implying that bronchoconstriction and MC activation
      were both cysLT dependent. Lys-ASA-induced cysLT generation and MC activation
      depended on platelet-adherent granulocytes and T-prostanoid (TP) receptors. Thus,
      lesions that impair the inducible generation of PGE2 remove control of
      platelet/granulocyte interactions and TP-receptor-dependent cysLT production,
      permitting MC activation in response to COX-1 inhibition. The findings suggest
      applications of antiplatelet drugs or TP receptor antagonists for the treatment
      of AERD. 

PMID- 24085851
TI  - Convergence in feeding posture occurs through different genetic loci in
      independently evolved cave populations of Astyanax mexicanus.
AB  - When an organism colonizes a new environment, it needs to adapt both
      morphologically and behaviorally to survive and thrive. Although recent progress
      has been made in understanding the genetic architecture underlying morphological
      evolution, behavioral evolution is poorly understood. Here, we use the Mexican
      cavefish, Astyanax mexicanus, to study the genetic basis for convergent evolution
      of feeding posture. When river-dwelling surface fish became entrapped in the
      caves, they were confronted with dramatic changes in the availability and type of
      food source and in their ability to perceive it. In this setting, multiple
      independent populations of cavefish exhibit an altered feeding posture compared
      with their ancestral surface forms. We determined that this behavioral change in
      feeding posture is not due to changes in cranial facial morphology, body depth,
      or to take advantage of the expansion in the number of taste buds. Quantitative
      genetic analysis demonstrates that two different cave populations have evolved
      similar feeding postures through a small number of genetic changes, some of which
      appear to be distinct. This work indicates that independently evolved populations
      of cavefish can evolve the same behavioral traits to adapt to similar
      environmental challenges by modifying different sets of genes. 

PMID- 24085852
TI  - Calpain-dependent cytoskeletal rearrangement exploited for anthrax toxin
      endocytosis.
AB  - The protective antigen component of Bacillus anthracis toxins can interact with
      at least three distinct proteins on the host cell surface, capillary
      morphogenesis gene 2 (CMG2), tumor endothelial marker 8, and beta1-integrin, and,
      with the assistance of other host proteins, enters targeted cells by receptor
      mediated endocytosis. Using an antisense-based phenotypic screen, we discovered
      the role of calpains in this process. We show that functions of a ubiquitous
      Ca(2+)-dependent cysteine protease, calpain-2, and of the calpain substrate talin
      1 are exploited for association of anthrax toxin and its principal receptor,
      CMG2, with higher-order actin filaments and consequently for toxin entry into
      host cells. Down-regulated expression of calpain-2 or talin-1, or pharmacological
      interference with calpain action, did not affect toxin binding but reduced
      endocytosis and increased the survival of cells exposed to anthrax lethal toxin.
      Adventitious expression of wild-type talin-1 promoted toxin endocytosis and
      lethality, whereas expression of a talin-1 mutant (L432G) that is insensitive to
      calpain cleavage did not. Disruption of talin-1, which links integrin-containing
      focal adhesion complexes to the actin cytoskeleton, facilitated association of
      toxin bound to its principal cell-surface receptor, CMG2, with higher-order actin
      filaments undergoing dynamic disassembly and reassembly during endocytosis. Our
      results reveal a mechanism by which a bacterial toxin uses constitutively
      occurring calpain-mediated cytoskeletal rearrangement for internalization. 

PMID- 24085854
TI  - Hemoptysis due to breath-hold diving following chemotherapy and lung irradiation:
      a differential diagnosis; with authors' reply.

PMID- 24085853
TI  - Quantitative apical membrane proteomics reveals vasopressin-induced actin
      dynamics in collecting duct cells.
AB  - In kidney collecting duct cells, filamentous actin (F-actin) depolymerization is
      a critical step in vasopressin-induced trafficking of aquaporin-2 to the apical
      plasma membrane. However, the molecular components of this response are largely
      unknown. Using stable isotope-based quantitative protein mass spectrometry and
      surface biotinylation, we identified 100 proteins that showed significant
      abundance changes in the apical plasma membrane of mouse cortical collecting duct
      cells in response to vasopressin. Fourteen of these proteins are involved in
      actin cytoskeleton regulation, including actin itself, 10 actin-associated
      proteins, and 3 regulatory proteins. Identified were two integral membrane
      proteins (Clmn, Nckap1) and one actin-binding protein (Mpp5) that link F-actin to
      the plasma membrane, five F-actin end-binding proteins (Arpc2, Arpc4, Gsn, Scin,
      and Capzb) involved in F-actin reorganization, and two actin adaptor proteins
      (Dbn1, Lasp1) that regulate actin cytoskeleton organization. There were also
      protease (Capn1), protein kinase (Cdc42bpb), and Rho guanine nucleotide exchange
      factor 2 (Arhgef2) that mediate signal-induced F-actin changes. Based on these
      findings, we devised a live-cell imaging method to observe vasopressin-induced F
      actin dynamics in polarized mouse cortical collecting duct cells. In response to
      vasopressin, F-actin gradually disappeared near the center of the apical plasma
      membrane while consolidating laterally near the tight junction. This F-actin
      peripheralization was blocked by calcium ion chelation. Vasopressin-induced
      apical aquaporin-2 trafficking and forskolin-induced water permeability increase
      were blocked by F-actin disruption. In conclusion, we identified a vasopressin
      regulated actin network potentially responsible for vasopressin-induced apical F
      actin dynamics that could explain regulation of apical aquaporin-2 trafficking
      and water permeability increase. 

PMID- 24085855
TI  - Advancing research in the era of healthcare reform: the 19th annual HMO Research
      Network Conference, April 16-18, 2013, San Francisco, California.

PMID- 24086041
TI  - Signaling by the TGFbeta superfamily.

PMID- 24086040
TI  - VEGFR and type-V RTK activation and signaling.
AB  - Vascular endothelial growth factor receptors (VEGFRs) in vertebrates play
      essential roles in the regulation of angiogenesis and lymphangiogenesis. VEGFRs
      belong to the receptor-type tyrosine kinase (RTK) supergene family. They consist
      of a ligand-binding region with seven immunoglobulin (7 Ig) -like domains, a
      trans-membrane (TM) domain, and a tyrosine kinase (TK) domain with a long kinase
      insert (KI) (also known as a type-V RTK). Structurally, VEGFRs are distantly
      related to the members of the M-colony stimulating factor receptor/platelet
      derived growth factor receptor (CSFR)/(PDGFR) family, which have five
      immunoglobulin (5 Ig)-like domains. However, signal transduction in VEGFRs
      significantly differs from that in M-CSFR/PDGFRs. VEGFR2, the major signal
      transducer for angiogenesis, preferentially uses the phospholipase Cgamma-protein
      kinase C (PLC-gamma-PKC)-MAPK pathway, whereas M-CSFR/PDGFRs use the PI3 kinase
      Ras-MAPK pathway for cell proliferation. In phylogenetic development, the VEGFR
      like receptor in nonvertebrates appears to be the ancestor of the 7 Ig- and 5 Ig
      RTK families because most nonvertebrates have only a single 7 Ig-RTK gene. In
      mammals, VEGFRs are deeply involved in pathological angiogenesis, including
      cancer and inflammation. Thus, an efficient inhibitor targeting VEGFRs could be
      useful in suppressing various diseases. 

PMID- 24086039
TI  - Receptor tyrosine kinases in the nucleus.
AB  - To date, 18 distinct receptor tyrosine kinases (RTKs) are reported to be
      trafficked from the cell surface to the nucleus in response to ligand binding or
      heterologous agonist exposure. In most cases, an intracellular domain (ICD)
      fragment of the receptor is generated at the cell surface and translocated to the
      nucleus, whereas for a few others the intact receptor is translocated to the
      nucleus. ICD fragments are generated by several mechanisms, including
      proteolysis, internal translation initiation, and messenger RNA (mRNA) splicing.
      The most prevalent mechanism is intramembrane cleavage by gamma-secretase. In
      some cases, more than one mechanism has been reported for the nuclear
      localization of a specific RTK. The generation and use of RTK ICD fragments to
      directly communicate with the nucleus and influence gene expression parallels the
      production of ICD fragments by a number of non-RTK cell-surface molecules that
      also influence cell proliferation. This review will be focused on the individual
      RTKs and to a lesser extent on other growth-related cell-surface transmembrane
      proteins. 

PMID- 24086042
TI  - Nucleotide excision repair in eukaryotes.
AB  - Nucleotide excision repair (NER) is the main pathway used by mammals to remove
      bulky DNA lesions such as those formed by UV light, environmental mutagens, and
      some cancer chemotherapeutic adducts from DNA. Deficiencies in NER are associated
      with the extremely skin cancer-prone inherited disorder xeroderma pigmentosum.
      Although the core NER reaction and the factors that execute it have been known
      for some years, recent studies have led to a much more detailed understanding of
      the NER mechanism, how NER operates in the context of chromatin, and how it is
      connected to other cellular processes such as DNA damage signaling and
      transcription. This review emphasizes biochemical, structural, cell biological,
      and genetic studies since 2005 that have shed light on many aspects of the NER
      pathway. 

PMID- 24086043
TI  - Advances in understanding the complex mechanisms of DNA interstrand cross-link
      repair.
AB  - DNA interstrand cross-links (ICLs) are lesions caused by a variety of endogenous
      metabolites, environmental exposures, and cancer chemotherapeutic agents that
      have two reactive groups. The common feature of these diverse lesions is that two
      nucleotides on opposite strands are covalently joined. ICLs prevent the
      separation of two DNA strands and therefore essential cellular processes
      including DNA replication and transcription. ICLs are mainly detected in S phase
      when a replication fork stalls at an ICL. Damage signaling and repair of ICLs are
      promoted by the Fanconi anemia pathway and numerous posttranslational
      modifications of DNA repair and chromatin structural proteins. ICLs are also
      detected and repaired in nonreplicating cells, although the mechanism is less
      clear. A unique feature of ICL repair is that both strands of DNA must be incised
      to completely remove the lesion. This is accomplished in sequential steps to
      prevent creating multiple double-strand breaks. Unhooking of an ICL from one
      strand is followed by translesion synthesis to fill the gap and create an intact
      duplex DNA, harboring a remnant of the ICL. Removal of the lesion from the second
      strand is likely accomplished by nucleotide excision repair. Inadequate repair of
      ICLs is particularly detrimental to rapidly dividing cells, explaining the bone
      marrow failure characteristic of Fanconi anemia and why cross-linking agents are
      efficacious in cancer therapy. Herein, recent advances in our understanding of
      ICLs and the biological responses they trigger are discussed. 

PMID- 24086044
TI  - Lipid sorting and multivesicular endosome biogenesis.
AB  - Intracellular organelles, including endosomes, show differences not only in
      protein but also in lipid composition. It is becoming clear from the work of many
      laboratories that the mechanisms necessary to achieve such lipid segregation can
      operate at very different levels, including the membrane biophysical properties,
      the interactions with other lipids and proteins, and the turnover rates or
      distribution of metabolic enzymes. In turn, lipids can directly influence the
      organelle membrane properties by changing biophysical parameters and by
      recruiting partner effector proteins involved in protein sorting and membrane
      dynamics. In this review, we will discuss how lipids are sorted in endosomal
      membranes and how they impact on endosome functions. 

PMID- 24086047
TI  - High-throughput analyses of IP3 receptor behavior.
AB  - Inositol 1,4,5-trisphosphate receptors (IP3Rs) are intracellular Ca(2+) channels.
      They are expressed in most animal cells and mediate release of Ca(2+) from the
      endoplasmic reticulum (ER) in response to the many stimuli that evoke formation
      of inositol 1,4,5-trisphosphate (IP3). The opening of individual IP3Rs causes
      small, transient, local increases in cytosolic Ca(2+) concentration, and these
      events are the fundamental units of Ca(2+) signaling. These openings allow Ca(2+)
      signals to be selectively delivered by individual channels to the specific Ca(2+)
      sensors that evoke cellular responses. Stimulation of IP3Rs by the Ca(2+) they
      release allows these tiny events to grow into much larger ones by recruitment of
      neighboring IP3Rs. Understanding how Ca(2+) effectively and specifically
      regulates so many cellular processes demands an understanding of the interplay
      between IP3 and Ca(2+) in controlling IP3R gating. Here, we briefly set the scene
      before introducing high-throughput methods that seek to address this issue. 

PMID- 24086048
TI  - Methods for analysis of the immune system in mouse cancer models.
AB  - Leukocytes of both the innate and adaptive immune systems can be a prominent
      feature of the tumor microenvironment. Mouse models of cancer that allow for
      tumor development in a host with a competent immune system can be investigated to
      gain a richer understanding of cancer immunobiology. Such studies not only
      provide biological insight but also can help forge new strategies for therapy and
      prognostication of patients. Here, we introduce several experimental protocols
      designed to analyze the immune phenotype of mouse cancer models. These include
      flow cytometric approaches to define tumor-infiltrating immune populations with
      precision and tissue-based assessments that preserve and reveal spatial
      dimensions of host-tumor cell interactions. An approach to study the immune
      suppressive capability of myeloid cells in the tumor microenvironment is also
      provided. 

PMID- 24086049
TI  - High-throughput functional assays of IP3-evoked Ca2+ release.
AB  - This protocol describes procedures for high-throughput functional analyses of
      inositol 1,4,5-trisphosphate receptors (IP3Rs) in permeabilized cells. The
      methods are applicable to native IP3Rs in a variety of cells and to recombinant
      IP3Rs stably expressed in DT40 cells in which gene disruption has abolished
      expression of endogenous IP3Rs. A low-affinity Ca(2+)-indicator (Mag-Fluo-4)
      trapped within the endoplasmic reticulum (ER) of permeabilized cells is used to
      report changes in luminal free Ca(2+) concentration. A fluorescence plate-reader
      equipped to allow automated additions permits rapid measurements of the Ca(2+)
      release evoked by IP3R. The procedure can be completed in 2-3 h. 

PMID- 24086046
TI  - Neurospora crassa, a model system for epigenetics research.
AB  - The filamentous fungus Neurospora crassa has provided a rich source of knowledge
      on epigenetic phenomena that would have been difficult or impossible to gain from
      other systems. Neurospora sports features found in higher eukaryotes but absent
      in both budding and fission yeast, including DNA methylation and H3K27
      methylation, and also has distinct RNA interference (RNAi)-based silencing
      mechanisms operating in mitotic and meiotic cells. This has provided an
      unexpected wealth of information on gene silencing systems. One silencing
      mechanism, named repeat-induced point mutation (RIP), has both epigenetic and
      genetic aspects and provided the first example of a homology-based genome defense
      system. A second silencing mechanism, named quelling, is an RNAi-based mechanism
      that results in silencing of transgenes and their native homologs. A third, named
      meiotic silencing, is also RNAi-based but is distinct from quelling in its time
      of action, targets, and apparent purpose. 

PMID- 24086045
TI  - Presynaptic membrane retrieval and endosome biology: defining molecularly
      heterogeneous synaptic vesicles.
AB  - The release and uptake of neurotransmitters by synaptic vesicles is a tightly
      controlled process that occurs in response to diverse stimuli at morphologically
      disparate synapses. To meet these architectural and functional synaptic demands,
      it follows that there should be diversity in the mechanisms that control their
      secretion and retrieval and possibly in the composition of synaptic vesicles
      within the same terminal. Here we pay particular attention to areas where such
      diversity is generated, such as the variance in exocytosis/endocytosis coupling,
      SNAREs defining functionally diverse synaptic vesicle populations and the adaptor
      dependent sorting machineries capable of generating vesicle diversity. We argue
      that there are various synaptic vesicle recycling pathways at any given synapse
      and discuss several lines of evidence that support the role of the endosome in
      synaptic vesicle recycling. 

PMID- 24086051
TI  - Multicolor flow cytometric analysis of immune cell subsets in tumor-bearing mice.
AB  - This protocol describes a procedure for obtaining a single-cell suspension from
      mouse spleen or solid tissue. Once a single-cell suspension is prepared,
      multicolor flow cytometry is used to identify subsets of immune cells in the
      samples of interest. This protocol can be used to evaluate the following immune
      cell populations, defined by the expression of certain cell surface molecules:
      total leukocytes, T lymphocytes and CD4(+) and CD8(+) T-cell subsets, B
      lymphocytes, natural killer cells, dendritic cells, and immature myeloid cells. 

PMID- 24086050
TI  - High-throughput fluorescence polarization assay of ligand binding to IP3
      receptors.
AB  - Fluorescence polarization (FP) allows quantification of the binding of a small
      fluorescent ligand to a larger protein because the free ligand rotates more
      rapidly than the bound form. This protocol describes an FP assay for the binding
      of fluorescein-labeled inositol 1,4,5-trisphosphate (IP3) to amino-terminal
      fragments of the IP3 receptor at different temperatures and in the presence of
      competing ligands. The method requires fluorescein-labeled IP3 and a plate-reader
      capable of FP measurements. The assay can measure low-affinity interactions in
      real time, it avoids use of radioactive materials, is nondestructive, and can
      resolve changes in Gibbs free energy (DeltaG degrees ), enthalpy (DeltaH degrees
      ), and entropy (DeltaS degrees ) that occur with ligand binding. It is applicable
      to any purified protein for which a fluorescent ligand is available. After
      optimization, the procedure can be completed in 1-6 h. 

PMID- 24086052
TI  - Preparation of cell-free splicing extracts from Saccharomyces cerevisiae.
AB  - Much of our understanding of the mechanism of splicing comes from the analysis of
      cell extracts able to carry out splicing complex formation and splicing reactions
      in vitro using exogenously added synthetic model pre-mRNA transcripts. This
      protocol describes the preparation of whole-cell extracts from the budding yeast
      Saccharomyces cerevisiae. These extracts can be used to dissect the biochemical
      steps of the splicing reaction and to determine the macromolecules, cofactors,
      and substrate features necessary for successful splicing. 

PMID- 24086053
TI  - Analysis of splicing in vitro using extracts of Saccharomyces cerevisiae.
AB  - In vitro splicing studies are a powerful means of investigating the requirements
      and mechanisms of action of the many components of the splicing apparatus. The
      ability to add and subtract components, purify activities, and reconstitute
      activity, as well as to expose the apparatus to chemical probes of various types,
      allows a far more mechanistically detailed view of the process to emerge than is
      available from genetic or in vivo studies alone. Two kinds of activities are
      assayed during in vitro splicing. The first concerns the chemical conversion of
      the substrate pre-mRNA into splicing intermediates and products and is usually
      visualized using a labeled substrate followed by separation on a denaturing gel.
      The second concerns the assembly of noncovalent complexes between the substrate
      and the myriad components of the splicing apparatus. This is also visualized
      using a labeled substrate, but the separation of complexes is achieved using
      native gel electrophoresis or gradient sedimentation. In this protocol, we
      describe the splicing reaction and its preparation for analysis by denaturing
      gels and native splicing complex gels. We also provide conditions for depletion
      of ATP, a critical cofactor that is hydrolyzed during numerous key steps in
      spliceosome assembly and splicing progression. 

PMID- 24086054
TI  - Analysis of splicing complexes on native gels.
AB  - Splicing requires a complex set of ATP-dependent macromolecular associations that
      lead to the rearrangement of just a few covalent bonds in the pre-mRNA substrate.
      Seeing only the covalent bonds breaking and forming is seeing only a very small
      part of the process. Analysis of native splicing complexes into which the
      radiolabeled substrate has been assembled, but not necessarily completely
      reacted, has provided a good understanding of the process. This protocol
      describes a gel method for detecting and analyzing yeast splicing complexes
      formed in vitro on a radiolabeled pre-mRNA substrate. Complexes formed during the
      splicing reaction are quenched by dilution and addition of an excess of RNA,
      which is thought to strip nonspecifically bound proteins from the labeled
      substrate RNA. After loading on a low-percentage, low-cross-linking ratio
      composite agarose-acrylamide gel (in 10% glycerol), labeled bands are detected.
      These can be extracted and shown to contain small nuclear RNAs (snRNAs) and
      partly reacted pre-mRNA. 

PMID- 24086055
TI  - Miniaturization of two-photon microscopy for imaging in freely moving animals.
AB  - This article describes the development and application of miniaturized two-photon
      excited fluorescence microscopes ("two-photon fiberscopes"). Two-photon
      fiberscopes have been developed with the aim of enabling high-resolution imaging
      of neural activity in freely behaving animals. They use fiber optics to deliver
      laser light for two-photon excitation. Their small front piece typically contains
      a miniature scanning mechanism and imaging optics. Two-photon fiberscopes can be
      made sufficiently small and lightweight to be carried by rats and mice and to
      allow virtually unrestricted movement within a behavioral arena. Typically
      mounted to the animal's skull above a cranial window, two-photon fiberscopes
      permit imaging of cells down to at least 250 um below the brain surface (e.g., in
      rat neocortex). In freely exploring animals, action-potential-evoked calcium
      transients can be imaged in individual somata of visual cortex neurons bulk
      labeled with a calcium indicator. Two-photon fiberscopes thus enable high
      resolution optical recording of neural activity with cellular resolution during
      natural behaviors. 

PMID- 24086056
TI  - Structure-function analysis of genetically defined neuronal populations.
AB  - Morphological and functional classification of individual neurons is a crucial
      aspect of the characterization of neuronal networks. Systematic structural and
      functional analysis of individual neurons is now possible using transgenic mice
      with genetically defined neurons that can be visualized in vivo or in brain slice
      preparations. Genetically defined neurons are useful for studying a particular
      class of neurons and also for more comprehensive studies of the neuronal content
      of a network. Specific subsets of neurons can be identified by fluorescence
      imaging of enhanced green fluorescent protein (eGFP) or another fluorophore
      expressed under the control of a cell-type-specific promoter. The advantages of
      such genetically defined neurons are not only their homogeneity and suitability
      for systematic descriptions of networks, but also their tremendous potential for
      cell-type-specific manipulation of neuronal networks in vivo. This article
      describes a selection of procedures for visualizing and studying the anatomy and
      physiology of genetically defined neurons in transgenic mice. We provide
      information about basic equipment, reagents, procedures, and analytical
      approaches for obtaining three-dimensional (3D) cell morphologies and determining
      the axonal input and output of genetically defined neurons. We exemplify with
      genetically labeled cortical neurons, but the procedures are applicable to other
      brain regions with little or no alterations. 

PMID- 24086057
TI  - Live imaging of neuroblast lineages within intact larval brains in Drosophila.
AB  - Neuroblasts are the precursors of the Drosophila central nervous system and
      undergo repeated physical and molecular asymmetric cell divisions. Live imaging
      of neuroblast lineages within intact Drosophila larval brains has dramatically
      improved our current understanding of basic cellular processes such as the
      establishment of cell polarity, spindle orientation, and cytokinesis. The
      analysis of mutant phenotypes using live imaging can enlarge our understanding of
      asymmetric neuroblast division and self-renewal. Although much live neuroblast
      imaging is performed using green fluorescent protein only, the generation of
      improved fluorescent proteins has led to an increase in the use of two-color
      imaging. Here we present a simple protocol for isolating and imaging larval brain
      neuroblasts. We describe procedures for the dissection and mounting of brains
      from third-instar Drosophila larvae in explant solution and their subsequent live
      imaging. The method provides a close approximation to the in vivo environment and
      produces data with high temporal and spatial resolutions. We also discuss
      potential problems and pitfalls and provide examples of how this technique is
      used. 

PMID- 24086058
TI  - Visualization of ubiquitin conjugates using ubiquitin-mediated fluorescence
      complementation analysis.
AB  - Ubiquitin-family peptide conjugation regulates the functions and stabilities of
      many proteins. Numerous cellular proteins are modified by covalent conjugation of
      ubiquitin-family peptides to specific lysine residues. These modifications
      provide a flexible means for regulating the properties of the substrate proteins.
      Because ubiquitin can be conjugated to substrate proteins at many different sites
      and in many topological configurations, these modifications have the potential to
      confer a wide range of functional states to the modified proteins. Ubiquitin
      conjugation is typically detected by immunoprecipitation of a putative substrate
      protein followed by immunoblotting to detect ubiquitin conjugated to the
      substrate. However, this assay cannot be used to detect ubiquitin conjugates in
      live cells. It is also difficult to determine the subcellular distribution of a
      specific ubiquitin conjugate using this approach. To visualize ubiquitin
      conjugates in live cells, we have developed the ubiquitin-mediated fluorescence
      complementation assay, which is based on the association of fragments of
      fluorescent proteins when ubiquitin fused to one fragment is conjugated to a
      substrate protein fused to a complementary fragment. This protocol focuses on the
      visualization of ubiquitin conjugated in cultured mammalian cells, but it can be
      adapted to any cell type or aerobically grown organism that can be genetically
      modified to express the fusion proteins. 

PMID- 24086059
TI  - Purification of functionalized quantum dots.
AB  - Semiconductor quantum dots (QDs) are fluorescent nanoparticles that can be used
      for biological imaging. Because of their brightness and photostability, which is
      far superior to those of organic dyes and fluorescent proteins, they can be
      detected at the single-particle level over long periods of time using standard
      fluorescence microscopy techniques. QDs can be conjugated to biomolecules and
      then used to track the motion of these molecules. Commercial, soluble QDs are
      available either unconjugated or functionalized with specific biomolecules. In
      the latter case, biomolecules such as streptavidin, Protein A, or antibodies are
      attached to the QD surface. Free biomolecules are often present in the QD
      solution, and these can be detrimental for live-cell imaging or other
      fluorescence assays. It is thus desirable to purify the functionalized QDs from
      these contaminating free biomolecules using size-exclusion chromatography. This
      article describes a simple procedure for purifying functionalized QDs using
      MicroSpin SR-400 columns. 

PMID- 24086060
TI  - Tracking individual membrane proteins using quantum dots.
AB  - Single-particle tracking of individual membrane molecules is now the method of
      choice to decipher the molecular organization of the plasma membrane. By labeling
      proteins or lipids with latex beads, 40-nm gold nanoparticles, or small organic
      fluorophores, it is possible to analyze the mechanisms controlling their lateral
      dynamics. Semiconductor quantum dots (QDs) provide several advantages for
      tracking membrane molecules: (1) Their size, which is intermediate between those
      of organic dyes (1-4 nm) and large beads (100 nm to 1 um), remains close to the
      molecular scale; (2) their photostability allows observation over long durations;
      (3) parallel detection of multiple spots in a field of view is easy; and (4)
      multicolor imaging is facilitated by their absorption properties. In general, the
      labeling of membrane molecules is based on the targeting of an extracellular
      epitope by a tagged antibody or ligand. By progressively decreasing the
      concentration of markers, a regime is reached where isolated tags can be detected
      and tracked. We present here a protocol based on the successive use of
      biotinylated primary antibodies and streptavidin-coated QDs. 

PMID- 24086061
TI  - Quantitative aspects of calcium fluorimetry.
AB  - Ca(2+) indicator dyes by necessity are Ca(2+) chelators, because it is the
      binding of Ca(2+) to dye molecules that induces the change in fluorescence on
      which the Ca(2+) signal is based. As chelators, once introduced into a cell, they
      contribute to cellular Ca(2+) buffering. It has been a question of much debate to
      what extent this added Ca(2+) buffer (exogenous Ca(2+) buffer) changes Ca(2+)
      homeostasis and the signals of interest. I discuss this problem here, emphasizing
      the distinction between the influence of the dyes on amplitudes (which may be not
      so severe) and on the dynamics of Ca(2+) signals (which may be drastic). Once the
      Ca(2+)-buffering action of dyes relative to intrinsic Ca(2+) buffers is
      understood for a given preparation, Ca(2+) dyes can be used as very versatile
      tools for studying both Ca(2+) concentrations and Ca(2+) fluxes. I describe in
      detail some of my own experiences in calibrating the indicator dye Fura-2. These
      refer exclusively to experiments in which the dye is loaded into the cell via a
      patch pipette because acetoxymethyl ester loading introduces problems that very
      often prohibit precise quantitative conclusions. 

PMID- 24086062
TI  - Measurement of calibration constants for quantitative calcium fluorimetry.
AB  - A careful calibration of the fluorescence setup is essential when using Fura-2
      for quantitative fluorimetry. The calibration procedure described here is used
      for experiments in which the indicator dye is introduced into the cell through a
      patch-clamp pipette. The fluorescence ratio is determined in whole-cell
      recordings for three different calibration parameters that reflect different
      [Ca(2+)]: very high (R1), intermediate (Keff), and zero (R0). 

PMID- 24086063
TI  - Embryonic heart progenitors and cardiogenesis.
AB  - The mammalian heart is a highly specialized organ, comprised of many different
      cell types arising from distinct embryonic progenitor populations during
      cardiogenesis. Three precursor populations have been identified to contribute to
      different myocytic and nonmyocytic cell lineages of the heart: cardiogenic
      mesoderm cells (CMC), the proepicardium (PE), and cardiac neural crest cells
      (CNCCs). This review will focus on molecular cues necessary for proper induction,
      expansion, and lineage-specific differentiation of these progenitor populations
      during cardiac development in vivo. Moreover, we will briefly discuss how the
      knowledge gained on embryonic heart progenitor biology can be used to develop
      novel therapeutic strategies for the management of congenital heart disease as
      well as for improvement of cardiac function in ischemic heart disease. 

PMID- 24086064
TI  - Myc function in Drosophila.
AB  - Drosophila contains a single MYC gene. Like its vertebrate homologs, it encodes a
      transcription factor that activates many targets, including prominently genes
      involved in ribosome biogenesis and translation. This activity makes Myc a
      central regulator of growth and/or proliferation of many cell types, such as
      imaginal disc cells, polyploid cells, stem cells, and blood cells. Importantly,
      not only does Myc act cell autonomously but it also affects the fate of adjacent
      cells and tissues. This potential of Myc is harnessed by many different signaling
      pathways, involving, among others, Wg, Dpp, Hpo, ecdysone, insulin, and mTOR. 

PMID- 24086066
TI  - The innate immune system and transplantation.
AB  - The sensitive and broadly reactive character of the innate immune system makes it
      liable to activation by stress factors other than infection. Thermal and
      metabolic stresses experienced during the transplantation procedure are
      sufficient to trigger the innate immune response and also augment adaptive
      immunity in the presence of foreign antigen on the donor organ. The resulting
      inflammatory and immune reactions combine to form a potent effector response that
      can lead to graft rejection. Here we examine the evidence that the complement and
      toll-like receptor systems are central to these pathways of injury and present a
      formidable barrier to transplantation. We review extensive information about the
      effector mechanisms that are mediated by these pathways, and bring together what
      is known about the damage-associated molecular patterns that initiate this
      sequence of events. Finally, we refer to two ongoing therapeutic trials that are
      evaluating the validity of these concepts in man. 

PMID- 24086067
TI  - Opportunistic infections--coming to the limits of immunosuppression?
AB  - Possible etiologies of infection in the solid organ recipient are diverse,
      ranging from common bacterial and viral pathogens to opportunistic pathogens that
      cause invasive disease only in immunocompromised hosts. The recognition of
      infectious syndromes in this population is limited by alterations in the clinical
      manifestations by immunosuppression. The risk of serious infections in the organ
      transplant patient is determined by the interaction between the patients' recent
      and distant epidemiological exposures and all factors that contribute to the
      patient's net state of immune suppression. This risk is altered by antimicrobial
      prophylaxis and changes in immunosuppressive therapies. In addition to the direct
      effects of infection, opportunistic infections, and the microbiome may adversely
      shape the host immune responses with diminished graft and patient survivals.
      Antimicrobial therapies are more complex than in the normal host with a
      significant incidence of drug toxicity and a propensity for drug interactions
      with the immunosuppressive agents used to maintain graft function. Rapid and
      specific microbiologic diagnosis is essential. Newer microbiologic assays have
      improved the diagnosis and management of opportunistic infections. These tools
      coupled with assays that assess immune responses to infection and to graft
      antigens may allow optimization of management for graft recipients in the future.

PMID- 24086065
TI  - Neuroblastoma and MYCN.
AB  - Neuroblastoma, the most common extracranial solid tumor of childhood, is thought
      to originate from undifferentiated neural crest cells. Amplification of the MYC
      family member, MYCN, is found in ~25% of cases and correlates with high-risk
      disease and poor prognosis. Currently, amplification of MYCN remains the best
      characterized genetic marker of risk in neuroblastoma. This article reviews roles
      for MYCN in neuroblastoma and highlights recent identification of other driver
      mutations. Strategies to target MYCN at the level of protein stability and
      transcription are also reviewed. 

PMID- 24086069
TI  - On "what makes transcutaneous electrical nerve stimulation work?..." Sluka KA,
      Bjordal JM, Marchand S, Rakel BA. Phys Ther. 2013;93:1397-1402.

PMID- 24086068
TI  - The inside story of Shigella invasion of intestinal epithelial cells.
AB  - As opposed to other invasive pathogens that reside into host cells in a parasitic
      mode, Shigella, the causative agent of bacillary dysentery, invades the colonic
      mucosa but does not penetrate further to survive into deeper tissues. Instead,
      Shigella invades, replicates, and disseminates within the colonic mucosa.
      Bacterial invasion and spreading in intestinal epithelium lead to the elicitation
      of inflammatory responses responsible for the tissue destruction and shedding in
      the environment for further infection of other hosts. In this article, we
      highlight specific features of the Shigella arsenal of virulence determinants
      injected by a type III secretion apparatus (T3SA) that point to the targeting of
      intestinal epithelial cells as a discrete route of invasion during the initial
      event of the infectious process. 

PMID- 24086070
TI  - Discussion podcast--"health services research funding and the Foundation for
      Physical Therapy".

PMID- 24086071
TI  - Comparison of combined transcatheter arterial chemoembolization and
      radiofrequency ablation with surgical resection by using propensity score
      matching in patients with hepatocellular carcinoma within Milan criteria.
AB  - PURPOSE: To retrospectively compare the outcome of combined transcatheter
      arterial chemoembolization (TACE) and radiofrequency ablation (RFA) (hereafter,
      TACE-RFA) with that of surgical resection (SR) in patients with hepatocellular
      carcinoma (HCC) within the Milan criteria. MATERIALS AND METHODS: Institutional
      review board approval and informed consent were obtained. From January 2000 to
      December 2010, 154 patients (mean age, 69.9 years; age range, 50-89 years; 107
      men, 47 women) underwent TACE-RFA, and 176 patients (mean age, 66.9 years; age
      range, 29-83 years; 128 men, 48 women) underwent SR. Patients with HCC who
      underwent TACE-RFA or SR were enrolled if they met the following inclusion
      criteria: no previous HCC treatment, one HCC lesion no larger than 5 cm or up to
      three nodules smaller than 3 cm without vascular invasion or extrahepatic
      metastasis, and Child-Pugh class A or B disease. Cumulative overall survival (OS)
      and disease-free survival (DFS) rates were compared after adjustment with
      propensity score matching. RESULTS: After this adjustment, OS rates were
      comparable between the groups (P = .393), but DFS was superior in the SR group (P
      < .048). Among patients with very early stage HCC (lesions <2 cm in diameter), OS
      and DFS rates in the SR group were significantly higher than those in the TACE
      RFA group (P < .001 and P = .008, respectively). However, adjustment with
      propensity score matching yielded comparable OS and DFS rates between the two
      groups (P = .348 and P = .614, respectively). CONCLUSION: TACE-RFA may be a
      viable alternative treatment for early-stage HCC when SR is not feasible.

PMID- 24086072
TI  - Advanced lung adenocarcinoma harboring a mutation of the epidermal growth factor
      receptor: CT findings after tyrosine kinase inhibitor therapy.
AB  - PURPOSE: To study chest computed tomography (CT) in tyrosine kinase inhibitor
      (TKI) treatment of epidermal growth factor receptor (EGFR)-mutant adenocarcinoma.
      MATERIALS AND METHODS: This retrospective study was approved by the institutional
      review board. Informed consent was waived. One hundred thirty consecutive
      patients with stage IV adenocarcinoma and EGFR mutations at a single tertiary
      center from November 2004 to April 2010 were enrolled retrospectively. CT images
      were analyzed with Response Evaluation Criteria in Solid Tumor guidelines. Target
      lesions were classified by size, type, axial location, and metastasis. Patients
      were followed after TKI therapy, and treatment response was classified as partial
      response, stable disease, or progressive disease. A Cox proportional hazards
      model was used to correlate baseline CT features and EGFR mutations with
      progression-free survival (PFS) and overall survival. RESULTS: All patients
      underwent TKI therapy after identifying exon mutations in the EGFR gene,
      comprising exon 19 deletion (19del) (n = 77), L858R (n = 43), and exon 18 (n =
      10). Outcomes were partial response (n = 103), stable disease (n = 22), and
      progressive disease (n = 5). In univariate analysis, PFS was significantly longer
      with small lesions (hazard ratio [HR], 1.02; 95% confidence interval [CI]: 1.01,
      1.03; P < .01), nodular main lesions (HR, 0.55; 95% CI: 0.34, 0.88; P = .01), or
      peripheral lesions (HR, 0.62; 95% CI: 0.42, 0.93; P = .02). In univariate
      analysis, PFS was significantly longer with smaller lesions (HR, 1.02; 95% CI:
      1.01, 1.03; P < .01), nodular main lesions (HR, 0.55; 95% CI: 0.34, 0.88; P =
      .01), peripheral lesions (HR, 0.62; 95% CI: 0.42, 0.93; P = .02), 19del (HR,
      0.33; 95% CI: 0.14, 0.77; P = .01), or L858R (HR, 0.39; 95% CI: 0.16, 0.97; P =
      .04). In multivariate analysis, PFS was significantly longer with 19del (HR,
      0.30; 95% CI: 0.11, 0.84; P = .02) and shorter with scattered metastases (HR,
      2.25; 95% CI: 1.44, 5.51; P < .01). CONCLUSION: Smaller nodular lesions,
      peripheral lesions, and 19del relate to longer PFS after EGFR TKI treatment.

PMID- 24086073
TI  - Cellular mechanisms of aneurysm occlusion after treatment with a flow diverter.
AB  - PURPOSE: To characterize the progression of healing across aneurysm necks
      following treatment with a flow diverter in a rabbit aneurysm model. MATERIALS
      AND METHODS: With institutional animal care and use committee approval, saccular
      aneurysms were created in 20 rabbits and treated with flow diverters. On days 1,
      3, and 7 and weeks 4 and 8 after implantation, the aneurysm and the device
      implanted vessel were harvested. En face staining of the gross specimen was
      performed for endothelial cells, endothelial progenitor cells, smooth muscle
      cells, and inflammatory cells. RESULTS: The parent artery segments covered by the
      flow diverters were completely devoid of endothelial cells at 1 and 3 days but
      had completely reendothelialized by 7 days. At all time points, the struts along
      the patent portions of the aneurysm necks harbored scattered tissue islands
      composed exclusively of inflammatory cells. At 4 and 8 weeks, all samples
      contiguous with the tissue along the parent arteries had translucent tissue
      present along the occluded segments of the aneurysm neck. The vast majority of
      endothelial cells were contiguous with the parent artery and had smooth muscle
      cells underlying them. Endothelial progenitor cells were not observed along the
      neck of any aneurysm. Aneurysm closure was noted only when complete or nearly
      complete endothelialization over the device struts was present. CONCLUSION: The
      initial event following flow diversion treatment is adherence of clusters of
      inflammatory cells across the aneurysm neck. Endothelialization is relatively
      delayed and derived exclusively from cells in the adjacent parent artery.

PMID- 24086074
TI  - Improved late gadolinium enhancement MR imaging for patients with implanted
      cardiac devices.
AB  - PURPOSE: To propose and test a modified wideband late gadolinium enhancement
      (LGE) magnetic resonance (MR) imaging technique to overcome hyperintensity image
      artifacts caused by implanted cardiac devices. MATERIALS AND METHODS: Written
      informed consent was obtained from all participants, and the HIPAA-compliant
      study protocol was approved by the institutional review board. Studies in
      phantoms and in a healthy volunteer were performed to test the hypothesis that
      the hyperintensity artifacts that are typically observed on LGE images in
      patients with implanted cardiac devices are caused by insufficient inversion of
      the affected myocardial signal. The conventional LGE MR imaging pulse sequence
      was modified by replacing the nonselective inversion pulse with a wideband
      inversion pulse. The modified LGE sequence, along with the conventional LGE
      sequence, was evaluated in 12 patients with implantable cardioverter
      defibrillators (ICDs) who were referred for cardiac MR imaging. RESULTS: The ICD
      causes 2-6 kHz in frequency shift at locations 5-10 cm away from the device. This
      off-resonance falls outside the typical spectral bandwidth of the nonselective
      inversion pulse used in conventional LGE, which results in the hyperintensity
      artifact. In 10 of the 12 patients, the conventional LGE technique produced
      severe, uninterpretable hyperintensity artifacts in the anterior and lateral
      portions of the left ventricular wall. These artifacts were eliminated with use
      of the wideband LGE sequence, thereby enabling confident evaluation of myocardial
      viability. CONCLUSION: The modified wideband LGE MR imaging technique eliminates
      the hyperintensity artifacts seen in patients with cardiac devices. The technique
      may enable LGE MR imaging in patients with cardiac devices, in whom LGE MR
      imaging otherwise could not be used for diagnosis.

PMID- 24086075
TI  - Estimating patient dose from x-ray tube output metrics: automated measurement of
      patient size from CT images enables large-scale size-specific dose estimates.
AB  - PURPOSE: To test the hypothesis that patient size can be accurately calculated
      from axial computed tomographic (CT) images, including correction for the effects
      of anatomy truncation that occur in routine clinical CT image reconstruction.
      MATERIALS AND METHODS: Institutional review board approval was obtained for this
      HIPAA-compliant study, with waiver of informed consent. Water-equivalent diameter
      (D(W)) was computed from the attenuation-area product of each image within 50
      adult CT scans of the thorax and of the abdomen and pelvis and was also measured
      for maximal field of view (FOV) reconstructions. Linear regression models were
      created to compare D(W) with the effective diameter (D(eff)) used to select size
      specific volume CT dose index (CTDI(vol)) conversion factors as defined in report
      204 of the American Association of Physicists in Medicine. Linear regression
      models relating reductions in measured D(W) to a metric of anatomy truncation
      were used to compensate for the effects of clinical image truncation. RESULTS: In
      the thorax, D(W)versus D(eff) had an R(2) of 0.51 (n = 200, 50 patients at four
      anatomic locations); in the abdomen and pelvis, R(2) was 0.90 (n = 150, 50
      patients at three anatomic locations). By correcting for image truncation, the
      proportion of clinically reconstructed images with an extracted D(W) within +/-5%
      of the maximal FOV D(W) increased from 54% to 90% in the thorax (n = 3602 images)
      and from 95% to 100% in the abdomen and pelvis (6181 images). CONCLUSION: The
      D(W) extracted from axial CT images is a reliable measure of patient size, and
      varying degrees of clinical image truncation can be readily corrected. Automated
      measurement of patient size combined with CT radiation exposure metrics may
      enable patient-specific dose estimation on a large scale.

PMID- 24086076
TI  - Studies of morphogens: keep calm and carry on.
AB  - Morphogens are signaling factors that direct cell fate and tissue development at
      a distance from their source, and various modes of transport and interpretation
      have been suggested for morphogens. The recent EMBO Workshop on 'Morphogen
      gradients', which took place in Oxford, UK in June 2013, centered on the
      formation and interpretation of such morphogen gradients during development. This
      meeting allowed an exchange of views in light of recent results. Here, we provide
      a brief overview of the talks, organized in relation to several major themes of
      discussion at the meeting: (1) morphogen gradient formation; (2) morphogen
      gradient interpretation; (3) signaling networks and feedback in morphogenesis;
      (4) emergence of patterns; (5) scaling of patterns; (6) the control of growth;
      and (7) new techniques in the field. 

PMID- 24086077
TI  - Getting the measure of things: the physical biology of stem cells.
AB  - In July 2013, the diverse fields of biology, physics and mathematics converged to
      discuss 'The Physical Biology of Stem Cells', the subject of the third annual
      symposium of the Cambridge Stem Cell Institute, UK. Two clear themes resonated
      throughout the meeting: the new insights gained from advances in the acquisition
      and interpretation of quantitative data; and the importance of 'thinking outside
      the nucleus' to consider physical influences on cell fate. 

PMID- 24086078
TI  - Sox proteins: regulators of cell fate specification and differentiation.
AB  - Sox transcription factors play widespread roles during development; however,
      their versatile funtions have a relatively simple basis: the binding of a Sox
      protein alone to DNA does not elicit transcriptional activation or repression,
      but requires binding of a partner transcription factor to an adjacent site on the
      DNA. Thus, the activity of a Sox protein is dependent upon the identity of its
      partner factor and the context of the DNA sequence to which it binds. In this
      Primer, we provide an mechanistic overview of how Sox family proteins function,
      as a paradigm for transcriptional regulation of development involving multi
      transcription factor complexes, and we discuss how Sox factors can thus regulate
      diverse processes during development. 

PMID- 24086081
TI  - Cone beam CT incidental findings: intracranial carotid artery calcification--a
      cause for concern.

PMID- 24086079
TI  - Brinker possesses multiple mechanisms for repression because its primary co
      repressor, Groucho, may be unavailable in some cell types.
AB  - Transcriptional repressors function primarily by recruiting co-repressors, which
      are accessory proteins that antagonize transcription by modifying chromatin
      structure. Although a repressor could function by recruiting just a single co
      repressor, many can recruit more than one, with Drosophila Brinker (Brk)
      recruiting the co-repressors CtBP and Groucho (Gro), in addition to possessing a
      third repression domain, 3R. Previous studies indicated that Gro is sufficient
      for Brk to repress targets in the wing, questioning why it should need to recruit
      CtBP, a short-range co-repressor, when Gro is known to be able to function over
      longer distances. To resolve this we have used genomic engineering to generate a
      series of brk mutants that are unable to recruit Gro, CtBP and/or have 3R
      deleted. These reveal that although the recruitment of Gro is necessary and can
      be sufficient for Brk to make an almost morphologically wild-type fly, it is
      insufficient during oogenesis, where Brk must utilize CtBP and 3R to pattern the
      egg shell appropriately. Gro insufficiency during oogenesis can be explained by
      its downregulation in Brk-expressing cells through phosphorylation downstream of
      EGFR signaling. 

PMID- 24086082
TI  - Development of 5123 intron-length polymorphic markers for large-scale genotyping
      applications in foxtail millet.
AB  - Generating genomic resources in terms of molecular markers is imperative in
      molecular breeding for crop improvement. Though development and application of
      microsatellite markers in large-scale was reported in the model crop foxtail
      millet, no such large-scale study was conducted for intron-length polymorphic
      (ILP) markers. Considering this, we developed 5123 ILP markers, of which 4049
      were physically mapped onto 9 chromosomes of foxtail millet. BLAST analysis of
      5123 expressed sequence tags (ESTs) suggested the function for ~71.5% ESTs and
      grouped them into 5 different functional categories. About 440 selected primer
      pairs representing the foxtail millet genome and the different functional groups
      showed high-level of cross-genera amplification at an average of ~85% in eight
      millets and five non-millet species. The efficacy of the ILP markers for
      distinguishing the foxtail millet is demonstrated by observed heterozygosity
      (0.20) and Nei's average gene diversity (0.22). In silico comparative mapping of
      physically mapped ILP markers demonstrated substantial percentage of sequence
      based orthology and syntenic relationship between foxtail millet chromosomes and
      sorghum (~50%), maize (~46%), rice (~21%) and Brachypodium (~21%) chromosomes.
      Hence, for the first time, we developed large-scale ILP markers in foxtail millet
      and demonstrated their utility in germplasm characterization, transferability,
      phylogenetics and comparative mapping studies in millets and bioenergy grass
      species. 

PMID- 24086084
TI  - New European Society of Cardiology guidelines published.

PMID- 24086083
TI  - Next-generation survey sequencing and the molecular organization of wheat
      chromosome 6B.
AB  - Common wheat (Triticum aestivum L.) is one of the most important cereals in the
      world. To improve wheat quality and productivity, the genomic sequence of wheat
      must be determined. The large genome size (~17 Gb/1 C) and the hexaploid status
      of wheat have hampered the genome sequencing of wheat. However, flow sorting of
      individual chromosomes has allowed us to purify and separately shotgun-sequence a
      pair of telocentric chromosomes. Here, we describe a result from the survey
      sequencing of wheat chromosome 6B (914 Mb/1 C) using massively parallel 454
      pyrosequencing. From the 4.94 and 5.51 Gb shotgun sequence data from the two
      chromosome arms of 6BS and 6BL, 235 and 273 Mb sequences were assembled to cover
      ~55.6 and 54.9% of the total genomic regions, respectively. Repetitive sequences
      composed 77 and 86% of the assembled sequences on 6BS and 6BL, respectively.
      Within the assembled sequences, we predicted a total of 4798 non-repetitive gene
      loci with the evidence of expression from the wheat transcriptome data. The
      numbers and chromosomal distribution patterns of the genes for tRNAs and
      microRNAs in wheat 6B were investigated, and the results suggested a significant
      involvement of DNA transposon diffusion in the evolution of these non-protein
      coding RNA genes. A comparative analysis of the genomic sequences of wheat 6B and
      monocot plants clearly indicated the evolutionary conservation of gene contents. 

PMID- 24086085
TI  - Coronary artery bypass grafting: Part 1--the evolution over the first 50 years.
AB  - Surgical treatment for angina pectoris was first proposed in 1899. Decades of
      experimental surgery for coronary artery disease finally led to the introduction
      of coronary artery bypass grafting (CABG) in 1964. Now that we are approaching 50
      years of CABG experience, it is appropriate to summarize the advancement of CABG
      into a procedure that is safe and efficient. This review provides a historical
      recapitulation of experimental surgery, the evolution of the surgical techniques
      and the utilization of CABG. Furthermore, data on contemporary clinical outcomes
      are discussed. 

PMID- 24086086
TI  - Coronary artery bypass grafting: Part 2--optimizing outcomes and future
      prospects.
AB  - Since first introduced in the mid-1960s, coronary artery bypass grafting (CABG)
      has become the standard of care for patients with coronary artery disease.
      Surprisingly, the fundamental surgical technique itself did not change much over
      time. Nevertheless, outcomes after CABG have dramatically improved over the first
      50 years. Randomized trials comparing percutaneous coronary intervention (PCI) to
      CABG have shown converging outcomes for select patient populations, providing
      more evidence for wider use of PCI. It is increasingly important to focus on the
      optimization of the short- and long-term outcomes of CABG and to reduce the level
      of invasiveness of this procedure. This review provides an overview on how new
      techniques and widespread consideration of evolving strategies have the potential
      to optimize outcomes after CABG. Such developments include off-pump CABG,
      clampless/anaortic CABG, minimally invasive CABG with or without extending to
      hybrid procedures, arterial revascularization, endoscopic vein harvesting,
      intraprocedural epiaortic scanning, graft flow assessment, and improved secondary
      prevention measures. In addition, this review represents a framework for future
      studies by summarizing the areas that need more rigorous clinical (randomized)
      evaluation. 

PMID- 24086087
TI  - GLP1 analogs as treatment of postprandial hypoglycemia following gastric bypass
      surgery: a potential new indication?
AB  - OBJECTIVE: The number of morbidly obese subjects submitted to bariatric surgery
      is rising worldwide. In a fraction of patients undergoing gastric bypass (GBP),
      episodes with late postprandial hypoglycemia (PPHG) develop 1-3 years after
      surgery. The pathogenesis of this phenomenon is not fully understood; meal
      induced rapid and exaggerated increases of circulating incretins and insulin
      appear to be at least partially responsible. Current treatments include low
      carbohydrate diets, inhibition of glucose intestinal uptake, reduction of insulin
      secretion with calcium channel blockers, somatostatin analogs, or diazoxide, a
      KATP channel opener. Even partial pancreatectomy has been advocated. In type 2
      diabetes, GLP1 analogs have a well-documented effect of stabilizing glucose
      levels without causing hypoglycemia. DESIGN: We explored GLP1 analogs as open
      treatment in five consecutive GBP cases seeking medical attention because of late
      postprandial hypoglycemic symptoms. RESULTS: Glucose measured in connection with
      the episodes in four of the cases had been 2.7, 2.5, 1.8, and 1.6 mmol/l
      respectively. The patients consistently described that the analogs eliminated
      their symptoms, which relapsed in four of the five patients when treatment was
      reduced/discontinued. The drug effect was further documented in one case by
      repeated 24-h continuous glucose measurements. CONCLUSION: These open,
      uncontrolled observations suggest that GLP1 analogs might provide a new treatment
      option in patients with problems of late PPHG.

PMID- 24086088
TI  - Heredity and lifestyle in the determination of between-subject variation in
      thyroid hormone levels in euthyroid men.
AB  - OBJECTIVE: Variation in thyroid hormone (TH) concentrations between subjects is
      greater than in a single subject over a prolonged period of time, suggesting an
      individual set point for thyroid function. We have previously shown that TH
      levels within normal range are associated with clinical indices such as bone
      mass, BMI, and heart rate. The aim of this study on young men was therefore to
      gain insight into the determinants of variation in TH levels among healthy
      subjects. METHODS: Healthy male siblings (n=941, 25-45 years) were recruited in a
      cross-sectional, population-based study; a history or treatment of thyroid
      disease and thyroid auto-immunity were exclusion criteria. A complete assessment
      of TH status was performed (TSH, free thyroxine (FT4), free triiodothyronine
      (FT3), thyroperoxidase, and thyroglobulin antibodies, reverse T3 (rT3), thyroid
      binding globulin (TBG), and urinary iodine levels). Genotyping was performed by
      TaqMan and KASP (KBiosciences) genotyping assays. RESULTS: (F)T4, rT3, and TBG
      had heritability estimates between 80 and 90%. Estimates were lower for (F)T3
      (60%) and lowest for TSH (49%). Significant associations were observed between
      different single-nucleotide polymorphisms (SNPs) in the thyroid pathway and TSH,
      FT4, ratio FT3:FT4, and rT3. Nevertheless, these SNPs only explain a limited part
      of the heredity. As to age and lifestyle-related factors, (F)T3 was negatively
      related to age and education level, positively to smoking and BMI (all P<0.0001)
      but not substantially to urinary iodine concentrations. Smoking was also
      negatively related to TSH and positively to FT4. CONCLUSION: Both genetic and
      lifestyle-related factors play a role in determining between-subject variation in
      TH levels in euthyroid young men, although genetic factors seem most important.

PMID- 24086090
TI  - Resonant acoustic radiation force optical coherence elastography.
AB  - We report on a resonant acoustic radiation force optical coherence elastography
      (ARF-OCE) technique that uses mechanical resonant frequency to characterize and
      identify tissues of different types. The linear dependency of the resonant
      frequency on the square root of Young's modulus was validated on silicone
      phantoms. Both the frequency response spectrum and the 3D imaging results from
      the agar phantoms with hard inclusions confirmed the feasibility of deploying the
      resonant frequency as a mechanical contrast for tissue imaging. Furthermore, the
      results of resonant ARF-OCE imaging of a post-mortem human coronary artery with
      atherosclerosis demonstrate the potential of the resonant ARF-OCE as a non
      invasive method for imaging and characterizing vulnerable plaques.

PMID- 24086089
TI  - Adrenocortical carcinoma: clinical outcomes and prognosis of 330 patients at a
      tertiary care center.
AB  - OBJECTIVE: Adrenocortical carcinoma (ACC) is a rare malignancy with a poor
      prognosis. Herein, we describe the clinical features and outcomes for a large
      series of ACC patients. DESIGN AND METHODS: Retrospective review of ACC patients
      seen at The University of Texas MD Anderson Cancer Center from 1998 through 2011.
      RESULTS: A total of 330 patients with median age at diagnosis of 48.5 years; 12
      (3.6%) patients were under 18 years. Hormonally functioning tumors represented
      41.8% (n=138) of all cases. Surgical resection for the primary tumor was done in
      275 (83.3%) patients (45 at MD Anderson (16.4%)). For those who had surgical
      resection, the median local-recurrence-free time was 1.04 years. Factors
      associated with local recurrence included positive surgical margins (P=0.007) and
      advanced disease stage (P=0.026). Median overall survival time for all patients
      was 3.21 years. Median survival times were 24.1, 6.08, 3.47, and 0.89 years for
      stages I, II, III, and IV respectively. In multivariable analysis, older age,
      functioning tumors, and higher disease stage remained significant prognostic
      factors associated with poor survival. CONCLUSION: ACC prognosis remains poor
      with the use of currently available treatments. Older age, functioning tumors,
      and incomplete resections are clinical factors associated with poor survival.
      Surgical expertise is important to achieve complete resections and to improve
      outcome.

PMID- 24086091
TI  - ORACLE INEQUALITIES FOR THE LASSO IN THE COX MODEL.
AB  - We study the absolute penalized maximum partial likelihood estimator in sparse,
      high-dimensional Cox proportional hazards regression models where the number of
      time-dependent covariates can be larger than the sample size. We establish oracle
      inequalities based on natural extensions of the compatibility and cone
      invertibility factors of the Hessian matrix at the true regression coefficients.
      Similar results based on an extension of the restricted eigenvalue can be also
      proved by our method. However, the presented oracle inequalities are sharper
      since the compatibility and cone invertibility factors are always greater than
      the corresponding restricted eigenvalue. In the Cox regression model, the Hessian
      matrix is based on time-dependent covariates in censored risk sets, so that the
      compatibility and cone invertibility factors, and the restricted eigenvalue as
      well, are random variables even when they are evaluated for the Hessian at the
      true regression coefficients. Under mild conditions, we prove that these
      quantities are bounded from below by positive constants for time-dependent
      covariates, including cases where the number of covariates is of greater order
      than the sample size. Consequently, the compatibility and cone invertibility
      factors can be treated as positive constants in our oracle inequalities.

PMID- 24086092
TI  - Bilingual parents' modeling of pragmatic language use in multiparty interactions.
AB  - Parental input represents an important source of language socialization.
      Particularly in bilingual contexts, parents may model pragmatic language use and
      metalinguistic strategies to highlight language differences. The present study
      examines multiparty interactions involving 28 bilingual English- and Marathi
      speaking parent-child pairs in the presence of monolingual bystanders (children's
      mean ages: 3;2 and 4;6). Their language use was analyzed during three sessions:
      parent and child alone, parent and child with the English speaker, and parent and
      child with the Marathi speaker. Parents demonstrated pragmatic differentiation by
      using relatively more of the bystander's language; however, children did not show
      this sensitivity. Further, parents used a variety of strategies to discuss
      language differences, such as providing and requesting translations; children
      translated most often in response to explicit requests. The results indicate that
      parents model pragmatic language differentiation as well as metalinguistic talk
      that may contribute to children's metalinguistic awareness.

PMID- 24086093
TI  - Research on the Mechanical Properties of "Z" Type Double-Decker Ball Bearings.
AB  - The mechanical model of a "Z" type double-decker ball bearing under the action of
      radial load is established in this paper on the basis of the Hertz contact
      theory. According to the security contact angle theory, the influences of inner
      and outer bearings' internal clearances on the bearing's static load carrying
      capacity, radial deformation, radial stiffness, and load distribution of balls
      are analyzed. This model is verified in both stationary and rotational loading
      experiments. Moreover, the simulation results show that the static load carrying
      capacity of Z type bearing is smaller than that of either inner bearing or outer
      bearing that is contributed to compose the Z type bearing. The static load
      carrying capacity of a Z type bearing reduces with the increase of the inner and
      outer bearings' internal clearance. These simulation results also indicate that
      the contact angle of the maximum loaded ball in the outer bearing easily exceeds
      its security contact angle compared with the inner bearing, which, as the main
      factor, may cause the Z type bearing to overload and to fail. In this sense, the
      investigated Z type bearings are unfit to apply to situations with heavy load,
      high speed, or high precision.

PMID- 24086094
TI  - Premature ventricular complexes and left atrial appendage dysfunction - another
      head on a many-headed hydra ?

PMID- 24086095
TI  - Left atrial appendage dysfunction in a patient with premature ventricular
      contractions - a risk factor for stroke?
AB  - A 16-year-old female with ventricular dysfunction and frequent ventricular
      arrhythmia presented with a cardioembolic stroke. Prior electrophysiology study
      and ablation was performed for ventricular tachycardia (VT). For remaining
      ventricular ectopy, the patient was maintained on carvedilol and mexiletine.
      After one year on this regimen, she presented with an acute stroke.
      Transesophageal echocardiography revealed no evidence of an intracardiac or
      ventricular thrombus but demonstrated markedly decreased left atrial appendage
      (LAA) flow velocity worsened during frequent premature ventricular contractions
      (PVC). In the absence of atrial fibrillation (AF), the LAA dysfunction was
      considered secondary to the frequent PVCs and was thought to be the underlying
      cause for the stroke. We present this case to highlight a potential under
      recognized association between LAA dysfunction and ventricular arrhythmia,
      similar to that observed with atrioventricular dyssynchronous pacing. 

PMID- 24086096
TI  - Posterior coronary vein as the substrate for an epicardial accessory pathway.
AB  - Catheter ablation of Wolff-Parkinson-White syndrome is associated with up to 5%
      of failure. Coronary sinus (CS) abnormalities or connections between CS
      myocardial coat and left ventricular epicardium are associated with posteroseptal
      and left posterior accessory pathways (AP). A 41-year-old patient with WPW
      syndrome was referred to our hospital after three unsuccessful ablations. The 12
      lead ECG suggested a left posteroseptal AP. CT imaging and electro-anatomic
      mapping showed a relationship between AP electrical course and CS posterior
      branch. This finding supports the hypothesis CSAPs lie in the myocardial coat
      around CS and represent an extensive connection between atrial and ventricular
      epicardial surface. 

PMID- 24086097
TI  - Sequential Anterograde and Retrograde Conduction Block during Radiofrequency
      Ablation of an Accessory Pathway.
AB  - We present an interesting image showing sequential loss of anterograde, and
      subsequently, retrograde conduction during radiofrequency ablation of an
      accessory pathway. We discuss the possible mechanisms and prior literature
      concerning this interesting finding. 

PMID- 24086098
TI  - Unintended Harm and Benefit of the Implantable Defibrillator in an Unfortunate 19
      Year-Old Male: Featuring a Sequence of Rare Life-threatening Complications of
      Cardiac Procedures.
AB  - All procedures have inherent risk. Our patient endured a sequence of rare life
      threatening complications from commonly preformed procedures. The sequence of
      these complications was; large pericardial effusion post implantable cardioverter
      defibrillator (ICD) implantation with echocardiographic signs of tamponade, left
      main narrowing post radiofrequency ablation, and late stent thrombosis post
      coronary intervention with a bare metal stent. All these occurred to one
      unfortunate young man. Furthermore, our patient demonstrated an unintended
      benefit of ICD which saved his life. 

PMID- 24086099
TI  - Sinus node dysfunction as the first manifestation of left ventricular
      noncompaction with multiple cardiac abnormalities.
AB  - Left ventricular noncompaction (LVNC) is a genetically heterogenous form of
      cardiomyopathy which may remain undiagnosed till adulthood due to the late
      presentation of typical symptoms such as dyspnea, congestion, ventricular
      arrhythmias and thromboembolism. Symptomatic bradycardia secondary to persistent
      sinus node dysfunction is very rare. Coexistent cardiac defects are common in
      children however in adults the disease is usually in isolated form. Here, we
      present a case of twenty-three year-old female LVNC patient with patent ductus
      arteriosus, bicuspid aortic valve and persistent sinus node dysfunction who
      presented with dizziness as the first manifestation of the disease. 

PMID- 24086100
TI  - Use of Electroanatomic Mapping Systems beyond Electrophysiologic Studies.

PMID- 24086101
TI  - Response to Letter: "Use of Electroanatomic Mapping Systems beyond
      Electrophysiologic Studies".

PMID- 24086102
TI  - SIMULATING BIOCHEMICAL SIGNALING NETWORKS IN COMPLEX MOVING GEOMETRIES.
AB  - Signaling networks regulate cellular responses to environmental stimuli through
      cascades of protein interactions. External signals can trigger cells to polarize
      and move in a specific direction. During migration, spatially localized activity
      of proteins is maintained. To investigate the effects of morphological changes on
      intracellular signaling, we developed a numerical scheme consisting of a cut cell
      finite volume spatial discretization coupled with level set methods to simulate
      the resulting advection-reaction-diffusion system. We then apply the method to
      several biochemical reaction networks in changing geometries. We found that a
      Turing instability can develop exclusively by cell deformations that maintain
      constant area. For a Turing system with a geometry-dependent single or double
      peak solution, simulations in a dynamically changing geometry suggest that a
      single peak solution is the only stable one, independent of the oscillation
      frequency. The method is also applied to a model of a signaling network in a
      migrating fibroblast.

PMID- 24086103
TI  - Descriptions of health states associated with increasing severity and frequency
      of hypoglycemia: a patient-level perspective.
AB  - AIMS: We sought to develop descriptions of health states associated with daytime
      and nocturnal hypoglycemia in a structured fashion from the patient's perspective
      under different combinations of severity and frequency of hypoglycemic events.
      METHODS: An expert meeting followed by two patient focus groups was used to
      develop comprehensive descriptions of acute consequences of severe and non
      severe, daytime and nocturnal hypoglycemia. Patients with diabetes (type 1 = 85,
      type 2 = 162) from a survey panel then validated these descriptions and assessed
      how often they worried and took different actions to prevent hypoglycemia.
      Severity and frequency of hypoglycemia were compared with respect to how often
      people worried and took actions to prevent an event. The effect of hypoglycemia
      on 35 different life activities was quantitatively compared for patients who had
      and had not experienced a severe hypoglycemic event. RESULTS: At least 95% of
      respondents agreed that the detailed patient-level descriptions of health states
      accurately reflected their experience of severe and non-severe, daytime and
      nocturnal hypoglycemia, thereby validating these descriptions. Respondents who
      had experienced a severe hypoglycemic event were generally more adversely
      affected in their worries and actions and life events than those who experienced
      only non-severe events; those who experienced nocturnal events were more affected
      than those who experienced only daytime events. CONCLUSION: The negative
      psychosocial consequences and undesirable compensatory behaviors arising from
      hypoglycemia underscore the importance of preventing severe episodes,
      particularly severe nocturnal episodes. These validated descriptions for
      hypoglycemia from the patient's perspective may also help inform future
      qualitative and quantitative research.

PMID- 24086104
TI  - Effect of pill burden on dosing preferences, willingness to pay, and likely
      adherence among patients with type 2 diabetes.
AB  - PURPOSE: To quantify willingness-to-pay (WTP) for reducing pill burden and dosing
      frequency among patients with type 2 diabetes mellitus (T2DM), and to examine the
      effect of dosing frequency and pill burden on likely medication adherence.
      PATIENTS AND METHODS: Participants were US adults with T2DM on oral
      antihyperglycemic therapy. Each patient completed an online discrete-choice
      experiment (DCE) with eight choice questions, each including a pair of
      hypothetical medication profiles. Each profile was defined by reduction in
      average glucose (AG), daily dosing, chance of mild-to-moderate stomach problems,
      frequency of hypoglycemia, weight change, incremental risk of congestive heart
      failure (CHF), and cost. Patients were asked to rate their likely adherence to
      the profiles presented in each question. Choice questions were based on a
      predetermined experimental design. Choice data were analyzed using random
      parameters logit. Likely treatment adherence was analyzed using a Heckman two
      stage model. RESULTS: Of the 1,114 patients who completed the survey, 90 had
      lower dosing burden (<5 pills/day taken once/day or as needed) for all
      medications, and 1,024 had higher dosing burden (>=5 pills/day or more than
      once/day). Reduction in AG was valued most highly by patients. Hypoglycemia,
      chance of mild-to-moderate stomach problems, weight change, incremental risk of
      CHF, and daily dosing were less valued. Patients with higher current dosing
      burden had lower WTP for more convenient dosing schedules than patients with
      lower current dosing burden. Changes in dosing and cost impacted likely
      adherence. The magnitude of the impact of dosing on likely adherence was higher
      for patients with lower current dosing burden than for patients with higher
      current dosing burden. CONCLUSION: Patients with T2DM were willing to pay for
      improvements in efficacy, side effects, and dosing. Patients' WTP for more
      convenient dosing depended on current dosing burden, as did the effect of these
      attributes on likely adherence.

PMID- 24086105
TI  - Real world outcomes of adding rapid-acting insulin versus switching to analog
      premix insulin among US patients with type 2 diabetes treated with insulin
      glargine.
AB  - INTRODUCTION: Patients with type 2 diabetes mellitus (T2DM) often require
      intensification of basal insulin therapy. This retrospective, observational study
      compared real-world outcomes in US patients with T2DM treated with insulin
      glargine who added a rapid-acting insulin (RAI) (basal-bolus approach) with those
      who switched to premixed insulin (PMX). METHODS: The national US IMPACT(r)
      database was used to identify data from adult patients (>=18 years of age) with
      T2DM who added bolus RAI to insulin glargine (GLA + RAI) or who switched from GLA
      to PMX between 2001 and 2009. A stringent 1:1 propensity score-matching method
      was used to address the selection bias by matching GLA + RAI patients and PMX
      patients. Clinical and economic outcomes were determined for 1 year after the
      initial pharmacy claim for RAI or for PMX. Outcomes included treatment
      persistence and adherence, average insulin doses, glycated hemoglobin (A1C)
      levels, the prevalence and incidence of hypoglycemia, and health care
      costs/utilization. Analysis was carried out using an intent-to-treat approach.
      RESULTS: The study included data from 746 propensity-matched patients (n = 373 in
      each cohort). Treatment persistence and adherence were higher in the GLA + RAI
      cohort. There was no significant difference in A1C reduction from baseline and
      the number of patients achieving target A1C levels of <7% in each cohort. The
      incidence of hypoglycemic events was also similar in both groups. However, during
      follow-up, many patients (48.8%) who initially switched from insulin glargine to
      PMX crossed back over to use GLA and/or RAI as part of their regimen. Health care
      costs and utilization levels were not significantly different. CONCLUSION:
      Clinical and economic outcomes were similar in T2DM patients who added RAI to GLA
      and in those who switched to PMX, but a basal-bolus strategy appears to be
      associated with better treatment persistence and adherence.

PMID- 24086106
TI  - Brain systems for probabilistic and dynamic prediction: computational specificity
      and integration.
AB  - A computational approach to functional specialization suggests that brain systems
      can be characterized in terms of the types of computations they perform, rather
      than their sensory or behavioral domains. We contrasted the neural systems
      associated with two computationally distinct forms of predictive model: a
      reinforcement-learning model of the environment obtained through experience with
      discrete events, and continuous dynamic forward modeling. By manipulating the
      precision with which each type of prediction could be used, we caused
      participants to shift computational strategies within a single spatial prediction
      task. Hence (using fMRI) we showed that activity in two brain systems (typically
      associated with reward learning and motor control) could be dissociated in terms
      of the forms of computations that were performed there, even when both systems
      were used to make parallel predictions of the same event. A region in parietal
      cortex, which was sensitive to the divergence between the predictions of the
      models and anatomically connected to both computational networks, is proposed to
      mediate integration of the two predictive modes to produce a single behavioral
      output. 

PMID- 24086107
TI  - The actress, the court, and what needs to be done to guarantee the future of
      clinical genomics.

PMID- 24086108
TI  - Fine-tuning metabolic switches.

PMID- 24086109
TI  - HIF1A reduces acute lung injury by optimizing carbohydrate metabolism in the
      alveolar epithelium.
AB  - BACKGROUND: While acute lung injury (ALI) contributes significantly to critical
      illness, it resolves spontaneously in many instances. The majority of patients
      experiencing ALI require mechanical ventilation. Therefore, we hypothesized that
      mechanical ventilation and concomitant stretch-exposure of pulmonary epithelia
      could activate endogenous pathways important in lung protection. METHODS AND
      FINDINGS: To examine transcriptional responses during ALI, we exposed pulmonary
      epithelia to cyclic mechanical stretch conditions--an in vitro model resembling
      mechanical ventilation. A genome-wide screen revealed a transcriptional response
      similar to hypoxia signaling. Surprisingly, we found that stabilization of
      hypoxia-inducible factor 1A (HIF1A) during stretch conditions in vitro or during
      ventilator-induced ALI in vivo occurs under normoxic conditions. Extension of
      these findings identified a functional role for stretch-induced inhibition of
      succinate dehydrogenase (SDH) in mediating normoxic HIF1A stabilization,
      concomitant increases in glycolytic capacity, and improved tricarboxylic acid
      (TCA) cycle function. Pharmacologic studies with HIF activator or inhibitor
      treatment implicated HIF1A-stabilization in attenuating pulmonary edema and lung
      inflammation during ALI in vivo. Systematic deletion of HIF1A in the lungs,
      endothelia, myeloid cells, or pulmonary epithelia linked these findings to
      alveolar-epithelial HIF1A. In vivo analysis of 13C-glucose metabolites utilizing
      liquid-chromatography tandem mass-spectrometry demonstrated that increases in
      glycolytic capacity, improvement of mitochondrial respiration, and concomitant
      attenuation of lung inflammation during ALI were specific for alveolar-epithelial
      expressed HIF1A. CONCLUSIONS: These studies reveal a surprising role for HIF1A in
      lung protection during ALI, where normoxic HIF1A stabilization and HIF-dependent
      control of alveolar-epithelial glucose metabolism function as an endogenous
      feedback loop to dampen lung inflammation.

PMID- 24086110
TI  - Hypoxic regulation of hand1 controls the fetal-neonatal switch in cardiac
      metabolism.
AB  - Cardiomyocytes are vulnerable to hypoxia in the adult, but adapted to hypoxia in
      utero. Current understanding of endogenous cardiac oxygen sensing pathways is
      limited. Myocardial oxygen consumption is determined by regulation of energy
      metabolism, which shifts from glycolysis to lipid oxidation soon after birth, and
      is reversed in failing adult hearts, accompanying re-expression of several
      "fetal" genes whose role in disease phenotypes remains unknown. Here we show that
      hypoxia-controlled expression of the transcription factor Hand1 determines oxygen
      consumption by inhibition of lipid metabolism in the fetal and adult
      cardiomyocyte, leading to downregulation of mitochondrial energy generation.
      Hand1 is under direct transcriptional control by HIF1alpha. Transgenic mice
      prolonging cardiac Hand1 expression die immediately following birth, failing to
      activate the neonatal lipid metabolising gene expression programme. Deletion of
      Hand1 in embryonic cardiomyocytes results in premature expression of these genes.
      Using metabolic flux analysis, we show that Hand1 expression controls
      cardiomyocyte oxygen consumption by direct transcriptional repression of lipid
      metabolising genes. This leads, in turn, to increased production of lactate from
      glucose, decreased lipid oxidation, reduced inner mitochondrial membrane
      potential, and mitochondrial ATP generation. We found that this pathway is active
      in adult cardiomyocytes. Up-regulation of Hand1 is protective in a mouse model of
      myocardial ischaemia. We propose that Hand1 is part of a novel regulatory pathway
      linking cardiac oxygen levels with oxygen consumption. Understanding hypoxia
      adaptation in the fetal heart may allow development of strategies to protect
      cardiomyocytes vulnerable to ischaemia, for example during cardiac ischaemia or
      surgery. 

PMID- 24086111
TI  - Mechanism of membranous tunnelling nanotube formation in viral genome delivery.
AB  - In internal membrane-containing viruses, a lipid vesicle enclosed by the
      icosahedral capsid protects the genome. It has been postulated that this internal
      membrane is the genome delivery device of the virus. Viruses built with this
      architectural principle infect hosts in all three domains of cellular life. Here,
      using a combination of electron microscopy techniques, we investigate
      bacteriophage PRD1, the best understood model for such viruses, to unveil the
      mechanism behind the genome translocation across the cell envelope. To deliver
      its double-stranded DNA, the icosahedral protein-rich virus membrane transforms
      into a tubular structure protruding from one of the 12 vertices of the capsid. We
      suggest that this viral nanotube exits from the same vertex used for DNA
      packaging, which is biochemically distinct from the other 11. The tube crosses
      the capsid through an aperture corresponding to the loss of the peripentonal P3
      major capsid protein trimers, penton protein P31 and membrane protein P16. The
      remodeling of the internal viral membrane is nucleated by changes in osmolarity
      and loss of capsid-membrane interactions as consequence of the de-capping of the
      vertices. This engages the polymerization of the tail tube, which is structured
      by membrane-associated proteins. We have observed that the proteo-lipidic tube in
      vivo can pierce the gram-negative bacterial cell envelope allowing the viral
      genome to be shuttled to the host cell. The internal diameter of the tube allows
      one double-stranded DNA chain to be translocated. We conclude that the assembly
      principles of the viral tunneling nanotube take advantage of proteo-lipid
      interactions that confer to the tail tube elastic, mechanical and functional
      properties employed also in other protein-membrane systems. 

PMID- 24086112
TI  - Up close and personal with an internal-membrane virus.

PMID- 24086114
TI  - Acupuncture and counselling for depression in primary care: a randomised
      controlled trial.
AB  - BACKGROUND: Depression is a significant cause of morbidity. Many patients have
      communicated an interest in non-pharmacological therapies to their general
      practitioners. Systematic reviews of acupuncture and counselling for depression
      in primary care have identified limited evidence. The aim of this study was to
      evaluate acupuncture versus usual care and counselling versus usual care for
      patients who continue to experience depression in primary care. METHODS AND
      FINDINGS: In a randomised controlled trial, 755 patients with depression (Beck
      Depression Inventory BDI-II score >= 20) were recruited from 27 primary care
      practices in the North of England. Patients were randomised to one of three arms
      using a ratio of 2.2.1 to acupuncture (302), counselling (302), and usual care
      alone (151). The primary outcome was the difference in mean Patient Health
      Questionnaire (PHQ-9) scores at 3 months with secondary analyses over 12 months
      follow-up. Analysis was by intention-to-treat. PHQ-9 data were available for 614
      patients at 3 months and 572 patients at 12 months. Patients attended a mean of
      ten sessions for acupuncture and nine sessions for counselling. Compared to usual
      care, there was a statistically significant reduction in mean PHQ-9 depression
      scores at 3 months for acupuncture (-2.46, 95% CI -3.72 to -1.21) and counselling
      (-1.73, 95% CI -3.00 to -0.45), and over 12 months for acupuncture (-1.55, 95% CI
      -2.41 to -0.70) and counselling (-1.50, 95% CI -2.43 to -0.58). Differences
      between acupuncture and counselling were not significant. In terms of
      limitations, the trial was not designed to separate out specific from non
      specific effects. No serious treatment-related adverse events were reported.
      CONCLUSIONS: In this randomised controlled trial of acupuncture and counselling
      for patients presenting with depression, after having consulted their general
      practitioner in primary care, both interventions were associated with
      significantly reduced depression at 3 months when compared to usual care alone.
      TRIAL REGISTRATION: Controlled-Trials.com ISRCTN63787732 Please see later in the
      article for the Editors' Summary.

PMID- 24086115
TI  - How to stir up trouble...while riding a rollercoaster.

PMID- 24086113
TI  - Serotype-specific changes in invasive pneumococcal disease after pneumococcal
      conjugate vaccine introduction: a pooled analysis of multiple surveillance sites.
AB  - BACKGROUND: Vaccine-serotype (VT) invasive pneumococcal disease (IPD) rates
      declined substantially following introduction of 7-valent pneumococcal conjugate
      vaccine (PCV7) into national immunization programs. Increases in non-vaccine
      serotype (NVT) IPD rates occurred in some sites, presumably representing serotype
      replacement. We used a standardized approach to describe serotype-specific IPD
      changes among multiple sites after PCV7 introduction. METHODS AND FINDINGS: Of 32
      IPD surveillance datasets received, we identified 21 eligible databases with rate
      data >= 2 years before and >= 1 year after PCV7 introduction. Expected annual
      rates of IPD absent PCV7 introduction were estimated by extrapolation using
      either Poisson regression modeling of pre-PCV7 rates or averaging pre-PCV7 rates.
      To estimate whether changes in rates had occurred following PCV7 introduction, we
      calculated site specific rate ratios by dividing observed by expected IPD rates
      for each post-PCV7 year. We calculated summary rate ratios (RRs) using random
      effects meta-analysis. For children <5 years old, overall IPD decreased by year 1
      post-PCV7 (RR 0.55, 95% CI 0.46-0.65) and remained relatively stable through year
      7 (RR 0.49, 95% CI 0.35-0.68). Point estimates for VT IPD decreased annually
      through year 7 (RR 0.03, 95% CI 0.01-0.10), while NVT IPD increased (year 7 RR
      2.81, 95% CI 2.12-3.71). Among adults, decreases in overall IPD also occurred but
      were smaller and more variable by site than among children. At year 7 after
      introduction, significant reductions were observed (18-49 year-olds [RR 0.52, 95%
      CI 0.29-0.91], 50-64 year-olds [RR 0.84, 95% CI 0.77-0.93], and >= 65 year-olds
      [RR 0.74, 95% CI 0.58-0.95]). CONCLUSIONS: Consistent and significant decreases
      in both overall and VT IPD in children occurred quickly and were sustained for 7
      years after PCV7 introduction, supporting use of PCVs. Increases in NVT IPD
      occurred in most sites, with variable magnitude. These findings may not represent
      the experience in low-income countries or the effects after introduction of
      higher valency PCVs. High-quality, population-based surveillance of serotype
      specific IPD rates is needed to monitor vaccine impact as more countries,
      including low-income countries, introduce PCVs and as higher valency PCVs are
      used. Please see later in the article for the Editors' Summary.

PMID- 24086116
TI  - Task-based core-periphery organization of human brain dynamics.
AB  - As a person learns a new skill, distinct synapses, brain regions, and circuits
      are engaged and change over time. In this paper, we develop methods to examine
      patterns of correlated activity across a large set of brain regions. Our goal is
      to identify properties that enable robust learning of a motor skill. We measure
      brain activity during motor sequencing and characterize network properties based
      on coherent activity between brain regions. Using recently developed algorithms
      to detect time-evolving communities, we find that the complex reconfiguration
      patterns of the brain's putative functional modules that control learning can be
      described parsimoniously by the combined presence of a relatively stiff temporal
      core that is composed primarily of sensorimotor and visual regions whose
      connectivity changes little in time and a flexible temporal periphery that is
      composed primarily of multimodal association regions whose connectivity changes
      frequently. The separation between temporal core and periphery changes over the
      course of training and, importantly, is a good predictor of individual
      differences in learning success. The core of dynamically stiff regions exhibits
      dense connectivity, which is consistent with notions of core-periphery
      organization established previously in social networks. Our results demonstrate
      that core-periphery organization provides an insightful way to understand how
      putative functional modules are linked. This, in turn, enables the prediction of
      fundamental human capacities, including the production of complex goal-directed
      behavior. 

PMID- 24086117
TI  - Modeling the effect of APC truncation on destruction complex function in
      colorectal cancer cells.
AB  - In colorectal cancer cells, APC, a tumor suppressor protein, is commonly
      expressed in truncated form. Truncation of APC is believed to disrupt degradation
      of beta-catenin, which is regulated by a multiprotein complex called the
      destruction complex. The destruction complex comprises APC, Axin, beta-catenin,
      serine/threonine kinases, and other proteins. The kinases CK1alpha and GSK 
      3beta, which are recruited by Axin, mediate phosphorylation of beta-catenin,
      which initiates its ubiquitination and proteosomal degradation. The mechanism of
      regulation of beta-catenin degradation by the destruction complex and the role of
      truncation of APC in colorectal cancer are not entirely understood. Through
      formulation and analysis of a rule-based computational model, we investigated the
      regulation of beta-catenin phosphorylation and degradation by APC and the effect
      of APC truncation on function of the destruction complex. The model integrates
      available mechanistic knowledge about site-specific interactions and
      phosphorylation of destruction complex components and is consistent with an array
      of published data. We find that the phosphorylated truncated form of APC can
      outcompete Axin for binding to beta-catenin, provided that Axin is limiting, and
      thereby sequester beta-catenin away from Axin and the Axin-recruited kinases
      CK1alpha and GSK -3beta. Full-length APC also competes with Axin for binding to
      beta-catenin; however, full-length APC is able, through its SAMP repeats, which
      bind Axin and which are missing in truncated oncogenic forms of APC, to bring
      beta-catenin into indirect association with Axin and Axin-recruited kinases.
      Because our model indicates that the positive effects of truncated APC on beta
      catenin levels depend on phosphorylation of APC, at the first 20-amino acid
      repeat, and because phosphorylation of this site is mediated by CK1epsilon, we
      suggest that CK1epsilon is a potential target for therapeutic intervention in
      colorectal cancer. Specific inhibition of CK1epsilon is predicted to limit
      binding of beta-catenin to truncated APC and thereby to reverse the effect of APC
      truncation.

PMID- 24086118
TI  - Analyzing and synthesizing phylogenies using tree alignment graphs.
AB  - Phylogenetic trees are used to analyze and visualize evolution. However, trees
      can be imperfect datatypes when summarizing multiple trees. This is especially
      problematic when accommodating for biological phenomena such as horizontal gene
      transfer, incomplete lineage sorting, and hybridization, as well as topological
      conflict between datasets. Additionally, researchers may want to combine
      information from sets of trees that have partially overlapping taxon sets. To
      address the problem of analyzing sets of trees with conflicting relationships and
      partially overlapping taxon sets, we introduce methods for aligning, synthesizing
      and analyzing rooted phylogenetic trees within a graph, called a tree alignment
      graph (TAG). The TAG can be queried and analyzed to explore uncertainty and
      conflict. It can also be synthesized to construct trees, presenting an
      alternative to supertrees approaches. We demonstrate these methods with two
      empirical datasets. In order to explore uncertainty, we constructed a TAG of the
      bootstrap trees from the Angiosperm Tree of Life project. Analysis of the
      resulting graph demonstrates that areas of the dataset that are unresolved in
      majority-rule consensus tree analyses can be understood in more detail within the
      context of a graph structure, using measures incorporating node degree and
      adjacency support. As an exercise in synthesis (i.e., summarization of a TAG
      constructed from the alignment trees), we also construct a TAG consisting of the
      taxonomy and source trees from a recent comprehensive bird study. We synthesized
      this graph into a tree that can be reconstructed in a repeatable fashion and
      where the underlying source information can be updated. The methods presented
      here are tractable for large scale analyses and serve as a basis for an
      alternative to consensus tree and supertree methods. Furthermore, the exploration
      of these graphs can expose structures and patterns within the dataset that are
      otherwise difficult to observe. 

PMID- 24086119
TI  - Tunable stochastic pulsing in the Escherichia coli multiple antibiotic resistance
      network from interlinked positive and negative feedback loops.
AB  - Cells live in uncertain, dynamic environments and have many mechanisms for
      sensing and responding to changes in their surroundings. However, sudden
      fluctuations in the environment can be catastrophic to a population if it relies
      solely on sensory responses, which have a delay associated with them. Cells can
      reconcile these effects by using a tunable stochastic response, where in the
      absence of a stressor they create phenotypic diversity within an isogenic
      population, but use a deterministic response when stressors are sensed. Here, we
      develop a stochastic model of the multiple antibiotic resistance network of
      Escherichia coli and show that it can produce tunable stochastic pulses in the
      activator MarA. In particular, we show that a combination of interlinked positive
      and negative feedback loops plays an important role in setting the dynamics of
      the stochastic pulses. Negative feedback produces a pulsatile response that is
      tunable, while positive feedback serves to amplify the effect. Our simulations
      show that the uninduced native network is in a parameter regime that is of low
      cost to the cell (taxing resistance mechanisms are expressed infrequently) and
      also elevated noise strength (phenotypic variability is high). The stochastic
      pulsing can be tuned by MarA induction such that variability is decreased once
      stresses are sensed, avoiding the detrimental effects of noise when an optimal
      MarA concentration is needed. We further show that variability in the expression
      of MarA can act as a bet hedging mechanism, allowing for survival in time-varying
      stress environments, however this effect is tunable to allow for a fully induced,
      deterministic response in the presence of a stressor. 

PMID- 24086120
TI  - Whisker movements reveal spatial attention: a unified computational model of
      active sensing control in the rat.
AB  - Spatial attention is most often investigated in the visual modality through
      measurement of eye movements, with primates, including humans, a widely-studied
      model. Its study in laboratory rodents, such as mice and rats, requires different
      techniques, owing to the lack of a visual fovea and the particular ethological
      relevance of orienting movements of the snout and the whiskers in these animals.
      In recent years, several reliable relationships have been observed between
      environmental and behavioural variables and movements of the whiskers, but the
      function of these responses, as well as how they integrate, remains unclear.
      Here, we propose a unifying abstract model of whisker movement control that has
      as its key variable the region of space that is the animal's current focus of
      attention, and demonstrate, using computer-simulated behavioral experiments, that
      the model is consistent with a broad range of experimental observations. A core
      hypothesis is that the rat explicitly decodes the location in space of whisker
      contacts and that this representation is used to regulate whisker drive signals.
      This proposition stands in contrast to earlier proposals that the modulation of
      whisker movement during exploration is mediated primarily by reflex loops. We go
      on to argue that the superior colliculus is a candidate neural substrate for the
      siting of a head-centred map guiding whisker movement, in analogy to current
      models of visual attention. The proposed model has the potential to offer a more
      complete understanding of whisker control as well as to highlight the potential
      of the rodent and its whiskers as a tool for the study of mammalian attention. 

PMID- 24086121
TI  - Frequency response of a protein to local conformational perturbations.
AB  - Signals created by local perturbations are known to propagate long distances
      through proteins via backbone connectivity and nonbonded interactions. In the
      current study, signal propagation from the flexible ligand binding loop to the
      rest of Protein Tyrosine Phosphatase 1B (PTP1B) was investigated using frequency
      response techniques. Using restrained Targeted Molecular Dynamics (TMD) potential
      on WPD and R loops, PTP1B was driven between its crystal structure conformations
      at different frequencies. Propagation of the local perturbation signal was
      manifested via peaks at the fundamental frequency and upper harmonics of 1/f
      distributed spectral density of atomic variables, such as Calpha atoms, dihedral
      angles, or polar interaction distances. Frequency of perturbation was adjusted
      high enough (simulation length >~10*period of a perturbation cycle) not to be
      clouded by random diffusional fluctuations, and low enough (<~0.8 ns(-1)) not to
      attenuate the propagating signal and enhance the contribution of the side-chains
      to the dissipation of the signals. Employing Discrete Fourier Transform (DFT) to
      TMD simulation trajectories of 16 cycles of conformational transitions at periods
      of 1.2 to 5 ns yielded Calpha displacements consistent with those obtained from
      crystal structures. Identification of the perturbed atomic variables by
      statistical t-tests on log-log scale spectral densities revealed the extent of
      signal propagation in PTP1B, while phase angles of the filtered trajectories at
      the fundamental frequency were used to cluster collectively fluctuating elements.
      Hydrophobic interactions were found to have a higher contribution to signal
      transduction between side-chains compared to the role of polar interactions. Most
      of in-phase fluctuating residues on the signaling pathway were found to have high
      identity among PTP domains, and located over a wide region of PTP1B including the
      allosteric site. Due to its simplicity and efficiency, the suggested technique
      may find wide applications in identification of signaling pathways of different
      proteins. 

PMID- 24086123
TI  - Ten simple rules for cultivating open science and collaborative R&D.

PMID- 24086122
TI  - Polycation-pi interactions are a driving force for molecular recognition by an
      intrinsically disordered oncoprotein family.
AB  - Molecular recognition by intrinsically disordered proteins (IDPs) commonly
      involves specific localized contacts and target-induced disorder to order
      transitions. However, some IDPs remain disordered in the bound state, a
      phenomenon coined "fuzziness", often characterized by IDP polyvalency, sequence
      insensitivity and a dynamic ensemble of disordered bound-state conformations.
      Besides the above general features, specific biophysical models for fuzzy
      interactions are mostly lacking. The transcriptional activation domain of the
      Ewing's Sarcoma oncoprotein family (EAD) is an IDP that exhibits many features of
      fuzziness, with multiple EAD aromatic side chains driving molecular recognition.
      Considering the prevalent role of cation-pi interactions at various protein
      protein interfaces, we hypothesized that EAD-target binding involves polycation-
      pi contacts between a disordered EAD and basic residues on the target. Herein we
      evaluated the polycation-pi hypothesis via functional and theoretical
      interrogation of EAD variants. The experimental effects of a range of EAD
      sequence variations, including aromatic number, aromatic density and charge
      perturbations, all support the cation-pi model. Moreover, the activity trends
      observed are well captured by a coarse-grained EAD chain model and a
      corresponding analytical model based on interaction between EAD aromatics and
      surface cations of a generic globular target. EAD-target binding, in the context
      of pathological Ewing's Sarcoma oncoproteins, is thus seen to be driven by a
      balance between EAD conformational entropy and favorable EAD-target cation-pi
      contacts. Such a highly versatile mode of molecular recognition offers a general
      conceptual framework for promiscuous target recognition by polyvalent IDPs. 

PMID- 24086127
TI  - Memory of infections: an emerging role for natural killer cells.

PMID- 24086124
TI  - Barcoding T cell calcium response diversity with methods for automated and
      accurate analysis of cell signals (MAAACS).
AB  - We introduce a series of experimental procedures enabling sensitive calcium
      monitoring in T cell populations by confocal video-microscopy. Tracking and post
      acquisition analysis was performed using Methods for Automated and Accurate
      Analysis of Cell Signals (MAAACS), a fully customized program that associates a
      high throughput tracking algorithm, an intuitive reconnection routine and a
      statistical platform to provide, at a glance, the calcium barcode of a population
      of individual T-cells. Combined with a sensitive calcium probe, this method
      allowed us to unravel the heterogeneity in shape and intensity of the calcium
      response in T cell populations and especially in naive T cells, which display
      intracellular calcium oscillations upon stimulation by antigen presenting cells. 

PMID- 24086128
TI  - Emerging and emerged pathogenic Candida species: beyond the Candida albicans
      paradigm.

PMID- 24086129
TI  - Highly significant antiviral activity of HIV-1 LTR-specific tre-recombinase in
      humanized mice.
AB  - Stable integration of HIV proviral DNA into host cell chromosomes, a hallmark and
      essential feature of the retroviral life cycle, establishes the infection
      permanently. Current antiretroviral combination drug therapy cannot cure HIV
      infection. However, expressing an engineered HIV-1 long terminal repeat (LTR)
      site-specific recombinase (Tre), shown to excise integrated proviral DNA in
      vitro, may provide a novel and highly promising antiviral strategy. We report
      here the conditional expression of Tre-recombinase from an advanced lentiviral
      self-inactivation (SIN) vector in HIV-infected cells. We demonstrate faithful
      transgene expression, resulting in accurate provirus excision in the absence of
      cytopathic effects. Moreover, pronounced Tre-mediated antiviral effects are
      demonstrated in vivo, particularly in humanized Rag2-/-gammac-/- mice engrafted
      with either Tre-transduced primary CD4+ T cells, or Tre-transduced CD34+
      hematopoietic stem and progenitor cells (HSC). Taken together, our data support
      the use of Tre-recombinase in novel therapy strategies aiming to provide a cure
      for HIV.

PMID- 24086130
TI  - Sustained autophagy contributes to measles virus infectivity.
AB  - The interplay between autophagy and intracellular pathogens is intricate as
      autophagy is an essential cellular response to fight against infections, whereas
      numerous microbes have developed strategies to escape this process or even
      exploit it to their own benefit. The fine tuned timing and/or selective molecular
      pathways involved in the induction of autophagy upon infections could be the
      cornerstone allowing cells to either control intracellular pathogens, or be
      invaded by them. We report here that measles virus infection induces successive
      autophagy signallings in permissive cells, via distinct and uncoupled molecular
      pathways. Immediately upon infection, attenuated measles virus induces a first
      transient wave of autophagy, via a pathway involving its cellular receptor CD46
      and the scaffold protein GOPC. Soon after infection, a new autophagy signalling
      is initiated which requires viral replication and the expression of the non
      structural measles virus protein C. Strikingly, this second autophagy signalling
      can be sustained overtime within infected cells, independently of the expression
      of C, but via a third autophagy input resulting from cell-cell fusion and the
      formation of syncytia. Whereas this sustained autophagy signalling leads to the
      autophagy degradation of cellular contents, viral proteins escape from
      degradation. Furthermore, this autophagy flux is ultimately exploited by measles
      virus to limit the death of infected cells and to improve viral particle
      formation. Whereas CD150 dependent virulent strains of measles virus are unable
      to induce the early CD46/GOPC dependent autophagy wave, they induce and exploit
      the late and sustained autophagy. Overall, our work describes distinct molecular
      pathways for an induction of self-beneficial sustained autophagy by measles
      virus. 

PMID- 24086131
TI  - Host adaptation is contingent upon the infection route taken by pathogens.
AB  - Evolution of pathogen virulence is affected by the route of infection. Also,
      alternate infection routes trigger different physiological responses on hosts,
      impinging on host adaptation and on its interaction with pathogens. Yet, how
      route of infection may shape adaptation to pathogens has not received much
      attention at the experimental level. We addressed this question through the
      experimental evolution of an outbred Drosophila melanogaster population infected
      by two different routes (oral and systemic) with Pseudomonas entomophila. The two
      selection regimes led to markedly different evolutionary trajectories. Adaptation
      to infection through one route did not protect from infection through the
      alternate route, indicating distinct genetic bases. Finally, relatively to the
      control population, evolved flies were not more resistant to bacteria other than
      Pseudomonas and showed higher susceptibility to viral infections. These
      specificities and trade-offs may contribute to the maintenance of genetic
      variation for resistance in natural populations. Our data shows that the
      infection route affects host adaptation and thus, must be considered in studies
      of host-pathogen interaction. 

PMID- 24086132
TI  - Dual analysis of the murine cytomegalovirus and host cell transcriptomes reveal
      new aspects of the virus-host cell interface.
AB  - Major gaps in our knowledge of pathogen genes and how these gene products
      interact with host gene products to cause disease represent a major obstacle to
      progress in vaccine and antiviral drug development for the herpesviruses. To
      begin to bridge these gaps, we conducted a dual analysis of Murine
      Cytomegalovirus (MCMV) and host cell transcriptomes during lytic infection. We
      analyzed the MCMV transcriptome during lytic infection using both classical cDNA
      cloning and sequencing of viral transcripts and next generation sequencing of
      transcripts (RNA-Seq). We also investigated the host transcriptome using RNA-Seq
      combined with differential gene expression analysis, biological pathway analysis,
      and gene ontology analysis. We identify numerous novel spliced and unspliced
      transcripts of MCMV. Unexpectedly, the most abundantly transcribed viral genes
      are of unknown function. We found that the most abundant viral transcript,
      recently identified as a noncoding RNA regulating cellular microRNAs, also codes
      for a novel protein. To our knowledge, this is the first viral transcript that
      functions both as a noncoding RNA and an mRNA. We also report that lytic
      infection elicits a profound cellular response in fibroblasts. Highly upregulated
      and induced host genes included those involved in inflammation and immunity, but
      also many unexpected transcription factors and host genes related to development
      and differentiation. Many top downregulated and repressed genes are associated
      with functions whose roles in infection are obscure, including host long
      intergenic noncoding RNAs, antisense RNAs or small nucleolar RNAs.
      Correspondingly, many differentially expressed genes cluster in biological
      pathways that may shed new light on cytomegalovirus pathogenesis. Together, these
      findings provide new insights into the molecular warfare at the virus-host
      interface and suggest new areas of research to advance the understanding and
      treatment of cytomegalovirus-associated diseases. 

PMID- 24086133
TI  - Atomic resolution description of the interaction between the nucleoprotein and
      phosphoprotein of Hendra virus.
AB  - Hendra virus (HeV) is a recently emerged severe human pathogen that belongs to
      the Henipavirus genus within the Paramyxoviridae family. The HeV genome is
      encapsidated by the nucleoprotein (N) within a helical nucleocapsid. Recruitment
      of the viral polymerase onto the nucleocapsid template relies on the interaction
      between the C-terminal domain, N(TAIL), of N and the C-terminal X domain, XD, of
      the polymerase co-factor phosphoprotein (P). Here, we provide an atomic
      resolution description of the intrinsically disordered N(TAIL) domain in its
      isolated state and in intact nucleocapsids using nuclear magnetic resonance (NMR)
      spectroscopy. Using electron microscopy, we show that HeV nucleocapsids form
      herringbone-like structures typical of paramyxoviruses. We also report the
      crystal structure of XD of P that consists of a three-helix bundle. We study the
      interaction between N(TAIL) and XD using NMR titration experiments and provide a
      detailed mapping of the reciprocal binding sites. We show that the interaction is
      accompanied by alpha-helical folding of the molecular recognition element of
      N(TAIL) upon binding to a hydrophobic patch on the surface of XD. Finally, using
      solution NMR, we investigate the interaction between intact nucleocapsids and XD.
      Our results indicate that monomeric XD binds to N(TAIL) without triggering an
      additional unwinding of the nucleocapsid template. The present results provide a
      structural description at the atomic level of the protein-protein interactions
      required for transcription and replication of HeV, and the first direct
      observation of the interaction between the X domain of P and intact nucleocapsids
      in Paramyxoviridae.

PMID- 24086134
TI  - Autoreactivity and exceptional CDR plasticity (but not unusual polyspecificity)
      hinder elicitation of the anti-HIV antibody 4E10.
AB  - The broadly-neutralizing anti-HIV antibody 4E10 recognizes an epitope in the
      membrane-proximal external region of the HIV envelope protein gp41. Previous
      attempts to elicit 4E10 by vaccination with envelope-derived or reverse
      engineered immunogens have failed. It was presumed that the ontogeny of 4E10
      equivalent responses was blocked by inherent autoreactivity and exceptional
      polyreactivity. We generated 4E10 heavy-chain knock-in mice, which displayed
      significant B cell dysregulation, consistent with recognition of autoantigen/s by
      4E10 and the presumption that tolerance mechanisms may hinder the elicitation of
      4E10 or 4E10-equivalent responses. Previously proposed candidate 4E10
      autoantigens include the mitochondrial lipid cardiolipin and a nuclear splicing
      factor, 3B3. However, using carefully-controlled assays, 4E10 bound only weakly
      to cardiolipin-containing liposomes, but also bound negatively-charged, non
      cardiolipin-containing liposomes comparably poorly. 4E10/liposome binding was
      predominantly mediated by electrostatic interactions rather than presumed
      hydrophobic interactions. The crystal structure of 4E10 free of bound ligands
      showed a dramatic restructuring of the combining site, occluding the HIV epitope
      binding site and revealing profound flexibility, but creating an electropositive
      pocket consistent with non-specific binding of phospholipid headgroups. These
      results strongly suggested that antigens other than cardiolipin mediate 4E10
      autoreactivity. Using a synthetic peptide library spanning the human proteome, we
      determined that 4E10 displays limited and focused, but unexceptional,
      polyspecificity. We also identified a novel autoepitope shared by three ER
      resident inositol trisphosphate receptors, validated through binding studies and
      immunohistochemistry. Tissue staining with 4E10 demonstrated reactivity
      consistent with the type 1 inositol trisphosphate receptor as the most likely
      candidate autoantigen, but is inconsistent with splicing factor 3B3. These
      results demonstrate that 4E10 recognition of liposomes competes with MPER
      recognition and that HIV antigen and autoepitope recognition may be distinct
      enough to permit eliciting 4E10-like antibodies, evading autoimmunity through
      directed engineering. However, 4E10 combining site flexibility, exceptional for a
      highly-matured antibody, may preclude eliciting 4E10 by conventional immunization
      strategies. 

PMID- 24086135
TI  - Inherited prion disease A117V is not simply a proteinopathy but produces prions
      transmissible to transgenic mice expressing homologous prion protein.
AB  - Prions are infectious agents causing fatal neurodegenerative diseases of humans
      and animals. In humans, these have sporadic, acquired and inherited aetiologies.
      The inherited prion diseases are caused by one of over 30 coding mutations in the
      human prion protein (PrP) gene (PRNP) and many of these generate infectious
      prions as evidenced by their experimental transmissibility by inoculation to
      laboratory animals. However, some, and in particular an extensively studied type
      of Gerstmann-Straussler-Scheinker syndrome (GSS) caused by a PRNP A117V mutation,
      are thought not to generate infectious prions and instead constitute prion
      proteinopathies with a quite distinct pathogenetic mechanism. Multiple attempts
      to transmit A117V GSS have been unsuccessful and typical protease-resistant PrP
      (PrP(Sc)), pathognomonic of prion disease, is not detected in brain. Pathogenesis
      is instead attributed to production of an aberrant topological form of PrP, C
      terminal transmembrane PrP ((Ctm)PrP). Barriers to transmission of prion strains
      from one species to another appear to relate to structural compatibility of PrP
      in host and inoculum and we have therefore produced transgenic mice expressing
      human 117V PrP. We found that brain tissue from GSS A117V patients did transmit
      disease to these mice and both the neuropathological features of prion disease
      and presence of PrP(Sc) was demonstrated in the brains of recipient transgenic
      mice. This PrP(Sc) rapidly degraded during laboratory analysis, suggesting that
      the difficulty in its detection in patients with GSS A117V could relate to post
      mortem proteolysis. We conclude that GSS A117V is indeed a prion disease although
      the relative contributions of (Ctm)PrP and prion propagation in neurodegeneration
      and their pathogenetic interaction remains to be established.

PMID- 24086136
TI  - Structural basis for the inhibition of histone deacetylase 8 (HDAC8), a key
      epigenetic player in the blood fluke Schistosoma mansoni.
AB  - The treatment of schistosomiasis, a disease caused by blood flukes parasites of
      the Schistosoma genus, depends on the intensive use of a single drug,
      praziquantel, which increases the likelihood of the development of drug-resistant
      parasite strains and renders the search for new drugs a strategic priority.
      Currently, inhibitors of human epigenetic enzymes are actively investigated as
      novel anti-cancer drugs and have the potential to be used as new anti-parasitic
      agents. Here, we report that Schistosoma mansoni histone deacetylase 8 (smHDAC8),
      the most expressed class I HDAC isotype in this organism, is a functional acetyl
      L-lysine deacetylase that plays an important role in parasite infectivity. The
      crystal structure of smHDAC8 shows that this enzyme adopts a canonical alpha/beta
      HDAC fold, with specific solvent exposed loops corresponding to insertions in the
      schistosome HDAC8 sequence. Importantly, structures of smHDAC8 in complex with
      generic HDAC inhibitors revealed specific structural changes in the smHDAC8
      active site that cannot be accommodated by human HDACs. Using a structure-based
      approach, we identified several small-molecule inhibitors that build on these
      specificities. These molecules exhibit an inhibitory effect on smHDAC8 but show
      reduced affinity for human HDACs. Crucially, we show that a newly identified
      smHDAC8 inhibitor has the capacity to induce apoptosis and mortality in
      schistosomes. Taken together, our biological and structural findings define the
      framework for the rational design of small-molecule inhibitors specifically
      interfering with schistosome epigenetic mechanisms, and further support an anti
      parasitic epigenome targeting strategy to treat neglected diseases caused by
      eukaryotic pathogens. 

PMID- 24086137
TI  - Absence of Siglec-H in MCMV infection elevates interferon alpha production but
      does not enhance viral clearance.
AB  - Plasmacytoid dendritic cells (pDCs) express the I-type lectin receptor Siglec-H
      and produce interferon alpha (IFNalpha), a critical anti-viral cytokine during
      the acute phase of murine cytomegalovirus (MCMV) infection. The ligands and
      biological functions of Siglec-H still remain incompletely defined in vivo. Thus,
      we generated a novel bacterial artificial chromosome (BAC)-transgenic "pDCre"
      mouse which expresses Cre recombinase under the control of the Siglec-H promoter.
      By crossing these mice with a Rosa26 reporter strain, a representative fraction
      of Siglec-H+ pDCs is terminally labeled with red fluorescent protein (RFP).
      Interestingly, systemic MCMV infection of these mice causes the downregulation of
      Siglec-H surface expression. This decline occurs in a TLR9- and MyD88-dependent
      manner. To elucidate the functional role of Siglec-H during MCMV infection, we
      utilized a novel Siglec-H deficient mouse strain. In the absence of Siglec-H, the
      low infection rate of pDCs with MCMV remained unchanged, and pDC activation was
      still intact. Strikingly, Siglec-H deficiency induced a significant increase in
      serum IFNalpha levels following systemic MCMV infection. Although Siglec-H
      modulates anti-viral IFNalpha production, the control of viral replication was
      unchanged in vivo. The novel mouse models will be valuable to shed further light
      on pDC biology in future studies.

PMID- 24086138
TI  - The suf iron-sulfur cluster synthesis pathway is required for apicoplast
      maintenance in malaria parasites.
AB  - The apicoplast organelle of the malaria parasite Plasmodium falciparum contains
      metabolic pathways critical for liver-stage and blood-stage development. During
      the blood stages, parasites lacking an apicoplast can grow in the presence of
      isopentenyl pyrophosphate (IPP), demonstrating that isoprenoids are the only
      metabolites produced in the apicoplast which are needed outside of the organelle.
      Two of the isoprenoid biosynthesis enzymes are predicted to rely on iron-sulfur
      (FeS) cluster cofactors, however, little is known about FeS cluster synthesis in
      the parasite or the roles that FeS cluster proteins play in parasite biology. We
      investigated two putative FeS cluster synthesis pathways (Isc and Suf) focusing
      on the initial step of sulfur acquisition. In other eukaryotes, these proteins
      can be located in multiple subcellular compartments, raising the possibility of
      cross-talk between the pathways or redundant functions. In P. falciparum, SufS
      and its partner SufE were found exclusively the apicoplast and SufS was shown to
      have cysteine desulfurase activity in a complementation assay. IscS and its
      effector Isd11 were solely mitochondrial, suggesting that the Isc pathway cannot
      contribute to apicoplast FeS cluster synthesis. The Suf pathway was disrupted
      with a dominant negative mutant resulting in parasites that were only viable when
      supplemented with IPP. These parasites lacked the apicoplast organelle and its
      organellar genome--a phenotype not observed when isoprenoid biosynthesis was
      specifically inhibited with fosmidomycin. Taken together, these results
      demonstrate that the Suf pathway is essential for parasite survival and has a
      fundamental role in maintaining the apicoplast organelle in addition to any role
      in isoprenoid biosynthesis.

PMID- 24086139
TI  - Assisted evolution enables HIV-1 to overcome a high TRIM5alpha-imposed genetic
      barrier to rhesus macaque tropism.
AB  - Diversification of antiretroviral factors during host evolution has erected
      formidable barriers to cross-species retrovirus transmission. This phenomenon
      likely protects humans from infection by many modern retroviruses, but it has
      also impaired the development of primate models of HIV-1 infection. Indeed,
      rhesus macaques are resistant to HIV-1, in part due to restriction imposed by the
      TRIM5alpha protein (rhTRIM5alpha). Initially, we attempted to derive rhTRIM5alpha
      resistant HIV-1 strains using two strategies. First, HIV-1 was passaged in
      engineered human cells expressing rhTRIM5alpha. Second, a library of randomly
      mutagenized capsid protein (CA) sequences was screened for mutations that reduced
      rhTRIM5alpha sensitivity. Both approaches identified several individual mutations
      in CA that reduced rhTRIM5alpha sensitivity. However, neither approach yielded
      mutants that were fully resistant, perhaps because the locations of the mutations
      suggested that TRIM5alpha recognizes multiple determinants on the capsid surface.
      Moreover, even though additive effects of various CA mutations on HIV-1
      resistance to rhTRIM5alpha were observed, combinations that gave full resistance
      were highly detrimental to fitness. Therefore, we employed an 'assisted
      evolution' approach in which individual CA mutations that reduced rhTRIM5alpha
      sensitivity without fitness penalties were randomly assorted in a library of
      viral clones containing synthetic CA sequences. Subsequent passage of the viral
      library in rhTRIM5alpha-expressing cells resulted in the selection of individual
      viral species that were fully fit and resistant to rhTRIM5alpha. These viruses
      encoded combinations of five mutations in CA that conferred complete or near
      complete resistance to the disruptive effects of rhTRIM5alpha on incoming viral
      cores, by abolishing recognition of the viral capsid. Importantly, HIV-1 variants
      encoding these CA substitutions and SIV(mac239) Vif replicated efficiently in
      primary rhesus macaque lymphocytes. These findings demonstrate that rhTRIM5alpha
      is difficult to but not impossible to evade, and doing so should facilitate the
      development of primate models of HIV-1 infection.

PMID- 24086140
TI  - Cross-serotype immunity induced by immunization with a conserved rhinovirus
      capsid protein.
AB  - Human rhinovirus (RV) infections are the principle cause of common colds and
      precipitate asthma and COPD exacerbations. There is currently no RV vaccine,
      largely due to the existence of ~150 strains. We aimed to define highly conserved
      areas of the RV proteome and test their usefulness as candidate antigens for a
      broadly cross-reactive vaccine, using a mouse infection model. Regions of the VP0
      (VP4+VP2) capsid protein were identified as having high homology across RVs.
      Immunization with a recombinant VP0 combined with a Th1 promoting adjuvant
      induced systemic, antigen specific, cross-serotype, cellular and humoral immune
      responses. Similar cross-reactive responses were observed in the lungs of
      immunized mice after infection with heterologous RV strains. Immunization
      enhanced the generation of heterosubtypic neutralizing antibodies and lung memory
      T cells, and caused more rapid virus clearance. Conserved domains of the RV
      capsid therefore induce cross-reactive immune responses and represent candidates
      for a subunit RV vaccine. 

PMID- 24086141
TI  - Histone chaperone NAP1 mediates sister chromatid resolution by counteracting
      protein phosphatase 2A.
AB  - Chromosome duplication and transmission into daughter cells requires the
      precisely orchestrated binding and release of cohesin. We found that the
      Drosophila histone chaperone NAP1 is required for cohesin release and sister
      chromatid resolution during mitosis. Genome-wide surveys revealed that NAP1 and
      cohesin co-localize at multiple genomic loci. Proteomic and biochemical analysis
      established that NAP1 associates with the full cohesin complex, but it also forms
      a separate complex with the cohesin subunit stromalin (SA). NAP1 binding to
      cohesin is cell-cycle regulated and increases during G2/M phase. This causes the
      dissociation of protein phosphatase 2A (PP2A) from cohesin, increased
      phosphorylation of SA and cohesin removal in early mitosis. PP2A depletion led to
      a loss of centromeric cohesion. The distinct mitotic phenotypes caused by the
      loss of either PP2A or NAP1, were both rescued by their concomitant depletion. We
      conclude that the balanced antagonism between NAP1 and PP2A controls cohesin
      dissociation during mitosis. 

PMID- 24086142
TI  - Rapid intrahost evolution of human cytomegalovirus is shaped by demography and
      positive selection.
AB  - Populations of human cytomegalovirus (HCMV), a large DNA virus, are highly
      polymorphic in patient samples, which may allow for rapid evolution within human
      hosts. To understand HCMV evolution, longitudinally sampled genomic populations
      from the urine and plasma of 5 infants with symptomatic congenital HCMV infection
      were analyzed. Temporal and compartmental variability of viral populations were
      quantified using high throughput sequencing and population genetics approaches.
      HCMV populations were generally stable over time, with ~88% of SNPs displaying
      similar frequencies. However, samples collected from plasma and urine of the same
      patient at the same time were highly differentiated with approximately 1700
      consensus sequence SNPs (1.2% of the genome) identified between compartments.
      This inter-compartment differentiation was comparable to the differentiation
      observed in unrelated hosts. Models of demography (i.e., changes in population
      size and structure) and positive selection were evaluated to explain the observed
      patterns of variation. Evidence for strong bottlenecks (>90% reduction in viral
      population size) was consistent among all patients. From the timing of the
      bottlenecks, we conclude that fetal infection occurred between 13-18 weeks
      gestational age in patients analyzed, while colonization of the urine compartment
      followed roughly 2 months later. The timing of these bottlenecks is consistent
      with the clinical histories of congenital HCMV infections. We next inferred that
      positive selection plays a small but measurable role in viral evolution within a
      single compartment. However, positive selection appears to be a strong and
      pervasive driver of evolution associated with compartmentalization, affecting >=
      34 of the 167 open reading frames (~20%) of the genome. This work offers the most
      detailed map of HCMV in vivo evolution to date and provides evidence that viral
      populations can be stable or rapidly differentiate, depending on host
      environment. The application of population genetic methods to these data provides
      clinically useful information, such as the timing of infection and compartment
      colonization.

PMID- 24086143
TI  - IL-17 attenuates degradation of ARE-mRNAs by changing the cooperation between AU
      binding proteins and microRNA16.
AB  - Interleukin 17A (IL-17), a mediator implicated in chronic and severe inflammatory
      diseases, enhances the production of pro-inflammatory mediators by attenuating
      decay of the encoding mRNAs. The decay of many of these mRNAs depends on proteins
      (AUBps) that target AU-rich elements in the 3'-untranslated region of mRNAs and
      facilitate either mRNA decay or stabilization. Here we show that AUBps and the
      target mRNA assemble in a novel ribonucleoprotein complex in the presence of
      microRNA16 (miR16), which leads to the degradation of the target mRNA. Notably,
      IL-17 attenuates miR16 expression and promotes the binding of stabilizing AUBps
      over that of destabilizing AUBps, reducing mRNA decay. These findings indicate
      that miR16 independently of a seed sequence, directs the competition between
      degrading and stabilizing AUBps for target mRNAs. Since AUBps affect expression
      of about 8% of the human transcriptome and miR16 is ubiquitously expressed, IL-17
      may in addition to inflammation affect many other cellular processes. 

PMID- 24086144
TI  - Cooperative interaction between phosphorylation sites on PERIOD maintains
      circadian period in Drosophila.
AB  - Circadian rhythms in Drosophila rely on cyclic regulation of the period (per) and
      timeless (tim) clock genes. The molecular cycle requires rhythmic phosphorylation
      of PER and TIM proteins, which is mediated by several kinases and phosphatases
      such as Protein Phosphatase-2A (PP2A) and Protein Phosphatase-1 (PP1). Here, we
      used mass spectrometry to identify 35 "phospho-occupied" serine/threonine
      residues within PER, 24 of which are specifically regulated by PP1/PP2A. We found
      that cell culture assays were not good predictors of protein function in flies
      and so we generated per transgenes carrying phosphorylation site mutations and
      tested for rescue of the per(01) arrhythmic phenotype. Surprisingly, most
      transgenes restore wild type rhythms despite carrying mutations in several
      phosphorylation sites. One particular transgene, in which T610 and S613 are
      mutated to alanine, restores daily rhythmicity, but dramatically lengthens the
      period to ~ 30 hrs. Interestingly, the single S613A mutation extends the period
      by 2-3 hours, while the single T610A mutation has a minimal effect, suggesting
      these phospho-residues cooperate to control period length. Conservation of S613
      from flies to humans suggests that it possesses a critical clock function, and
      mutational analysis of residues surrounding T610/S613 implicates the entire
      region in determining circadian period. Biochemical and immunohistochemical data
      indicate defects in overall phosphorylation and altered timely degradation of PER
      carrying the double or single S613A mutation(s). The PER-T610A/S613A mutant also
      alters CLK phosphorylation and CLK-mediated output. Lastly, we show that a
      mutation at a previously identified site, S596, is largely epistatic to S613A,
      suggesting that S613 negatively regulates phosphorylation at S596. Together these
      data establish functional significance for a new domain of PER, demonstrate that
      cooperativity between phosphorylation sites maintains PER function, and support a
      model in which specific phosphorylated regions regulate others to control
      circadian period.

PMID- 24086145
TI  - Meiotic recombination in Arabidopsis is catalysed by DMC1, with RAD51 playing a
      supporting role.
AB  - Recombination establishes the chiasmata that physically link pairs of homologous
      chromosomes in meiosis, ensuring their balanced segregation at the first meiotic
      division and generating genetic variation. The visible manifestation of genetic
      crossing-overs, chiasmata are the result of an intricate and tightly regulated
      process involving induction of DNA double-strand breaks and their repair through
      invasion of a homologous template DNA duplex, catalysed by RAD51 and DMC1 in most
      eukaryotes. We describe here a RAD51-GFP fusion protein that retains the ability
      to assemble at DNA breaks but has lost its DNA break repair capacity. This
      protein fully complements the meiotic chromosomal fragmentation and sterility of
      Arabidopsis rad51, but not rad51 dmc1 mutants. Even though DMC1 is the only
      active meiotic strand transfer protein in the absence of RAD51 catalytic
      activity, no effect on genetic map distance was observed in complemented rad51
      plants. The presence of inactive RAD51 nucleofilaments is thus able to fully
      support meiotic DSB repair and normal levels of crossing-over by DMC1. Our data
      demonstrate that RAD51 plays a supporting role for DMC1 in meiotic recombination
      in the flowering plant, Arabidopsis. 

PMID- 24086146
TI  - Genome-wide analysis of ZmDREB genes and their association with natural variation
      in drought tolerance at seedling stage of Zea mays L.
AB  - The worldwide production of maize (Zea mays L.) is frequently impacted by water
      scarcity and as a result, increased drought tolerance is a priority target in
      maize breeding programs. While DREB transcription factors have been demonstrated
      to play a central role in desiccation tolerance, whether or not natural sequence
      variations in these genes are associated with the phenotypic variability of this
      trait is largely unknown. In the present study, eighteen ZmDREB genes present in
      the maize B73 genome were cloned and systematically analyzed to determine their
      phylogenetic relationship, synteny with rice, maize and sorghum genomes; pattern
      of drought-responsive gene expression, and protein transactivation activity.
      Importantly, the association between the nucleic acid variation of each ZmDREB
      gene with drought tolerance was evaluated using a diverse population of maize
      consisting of 368 varieties from tropical and temperate regions. A significant
      association between the genetic variation of ZmDREB2.7 and drought tolerance at
      seedling stage was identified. Further analysis found that the DNA polymorphisms
      in the promoter region of ZmDREB2.7, but not the protein coding region itself,
      was associated with different levels of drought tolerance among maize varieties,
      likely due to distinct patterns of gene expression in response to drought stress.
      In vitro, protein-DNA binding assay demonstrated that ZmDREB2.7 protein could
      specifically interact with the target DNA sequences. The transgenic Arabidopsis
      overexpressing ZmDREB2.7 displayed enhanced tolerance to drought stress.
      Moreover, a favorable allele of ZmDREB2.7, identified in the drought-tolerant
      maize varieties, was effective in imparting plant tolerance to drought stress.
      Based upon these findings, we conclude that natural variation in the promoter of
      ZmDREB2.7 contributes to maize drought tolerance, and that the gene and its
      favorable allele may be an important genetic resource for the genetic improvement
      of drought tolerance in maize. 

PMID- 24086147
TI  - Nebula/DSCR1 upregulation delays neurodegeneration and protects against APP
      induced axonal transport defects by restoring calcineurin and GSK-3beta
      signaling.
AB  - Post-mortem brains from Down syndrome (DS) and Alzheimer's disease (AD) patients
      show an upregulation of the Down syndrome critical region 1 protein (DSCR1), but
      its contribution to AD is not known. To gain insights into the role of DSCR1 in
      AD, we explored the functional interaction between DSCR1 and the amyloid
      precursor protein (APP), which is known to cause AD when duplicated or
      upregulated in DS. We find that the Drosophila homolog of DSCR1, Nebula, delays
      neurodegeneration and ameliorates axonal transport defects caused by APP
      overexpression. Live-imaging reveals that Nebula facilitates the transport of
      synaptic proteins and mitochondria affected by APP upregulation. Furthermore, we
      show that Nebula upregulation protects against axonal transport defects by
      restoring calcineurin and GSK-3beta signaling altered by APP overexpression,
      thereby preserving cargo-motor interactions. As impaired transport of essential
      organelles caused by APP perturbation is thought to be an underlying cause of
      synaptic failure and neurodegeneration in AD, our findings imply that correcting
      calcineurin and GSK-3beta signaling can prevent APP-induced pathologies. Our data
      further suggest that upregulation of Nebula/DSCR1 is neuroprotective in the
      presence of APP upregulation and provides evidence for calcineurin inhibition as
      a novel target for therapeutic intervention in preventing axonal transport
      impairments associated with AD. 

PMID- 24086148
TI  - Ultra-sensitive sequencing reveals an age-related increase in somatic
      mitochondrial mutations that are inconsistent with oxidative damage.
AB  - Mitochondrial DNA (mtDNA) is believed to be highly vulnerable to age-associated
      damage and mutagenesis by reactive oxygen species (ROS). However, somatic mtDNA
      mutations have historically been difficult to study because of technical
      limitations in accurately quantifying rare mtDNA mutations. We have applied the
      highly sensitive Duplex Sequencing methodology, which can detect a single
      mutation among >10(7) wild type molecules, to sequence mtDNA purified from human
      brain tissue from both young and old individuals with unprecedented accuracy. We
      find that the frequency of point mutations increases ~5-fold over the course of
      80 years of life. Overall, the mutation spectra of both groups are comprised
      predominantly of transition mutations, consistent with misincorporation by DNA
      polymerase gamma or deamination of cytidine and adenosine as the primary
      mutagenic events in mtDNA. Surprisingly, G -> T mutations, considered the
      hallmark of oxidative damage to DNA, do not significantly increase with age. We
      observe a non-uniform, age-independent distribution of mutations in mtDNA, with
      the D-loop exhibiting a significantly higher mutation frequency than the rest of
      the genome. The coding regions, but not the D-loop, exhibit a pronounced
      asymmetric accumulation of mutations between the two strands, with G -> A and T 
      > C mutations occurring more often on the light strand than the heavy strand. The
      patterns and biases we observe in our data closely mirror the mutational spectrum
      which has been reported in studies of human populations and closely related
      species. Overall our results argue against oxidative damage being a major driver
      of aging and suggest that replication errors by DNA polymerase gamma and/or
      spontaneous base hydrolysis are responsible for the bulk of accumulating point
      mutations in mtDNA.

PMID- 24086149
TI  - Fusion of large-scale genomic knowledge and frequency data computationally
      prioritizes variants in epilepsy.
AB  - Curation and interpretation of copy number variants identified by genome-wide
      testing is challenged by the large number of events harbored in each personal
      genome. Conventional determination of phenotypic relevance relies on patterns of
      higher frequency in affected individuals versus controls; however, an increasing
      amount of ascertained variation is rare or private to clans. Consequently,
      frequency data have less utility to resolve pathogenic from benign. One solution
      is disease-specific algorithms that leverage gene knowledge together with variant
      frequency to aid prioritization. We used large-scale resources including Gene
      Ontology, protein-protein interactions and other annotation systems together with
      a broad set of 83 genes with known associations to epilepsy to construct a
      pathogenicity score for the phenotype. We evaluated the score for all annotated
      human genes and applied Bayesian methods to combine the derived pathogenicity
      score with frequency information from our diagnostic laboratory. Analysis
      determined Bayes factors and posterior distributions for each gene. We applied
      our method to subjects with abnormal chromosomal microarray results and confirmed
      epilepsy diagnoses gathered by electronic medical record review. Genes deleted in
      our subjects with epilepsy had significantly higher pathogenicity scores and
      Bayes factors compared to subjects referred for non-neurologic indications. We
      also applied our scores to identify a recently validated epilepsy gene in a
      complex genomic region and to reveal candidate genes for epilepsy. We propose a
      potential use in clinical decision support for our results in the context of
      genome-wide screening. Our approach demonstrates the utility of integrative data
      in medical genomics. 

PMID- 24086150
TI  - The highly prolific phenotype of Lacaune sheep is associated with an ectopic
      expression of the B4GALNT2 gene within the ovary.
AB  - Prolific sheep have proven to be a valuable model to identify genes and mutations
      implicated in female fertility. In the Lacaune sheep breed, large variation in
      litter size is genetically determined by the segregation of a fecundity major
      gene influencing ovulation rate, named FecL and its prolific allele FecL(L) . Our
      previous work localized FecL on sheep chromosome 11 within a locus of 1.1 Mb
      encompassing 20 genes. With the aim to identify the FecL gene, we developed a
      high throughput sequencing strategy of long-range PCR fragments spanning the
      locus of FecL(L) carrier and non-carrier ewes. Resulting informative markers
      defined a new 194.6 kb minimal interval. The reduced FecL locus contained only
      two genes, insulin-like growth factor 2 mRNA binding protein 1 (IGF2BP1) and beta
      1,4-N-acetyl-galactosaminyl transferase 2 (B4GALNT2), and we identified two SNP
      in complete linkage disequilibrium with FecL(L) . B4GALNT2 appeared as the best
      positional and expressional candidate for FecL, since it showed an ectopic
      expression in the ovarian follicles of FecL(L) /FecL(L) ewes at mRNA and protein
      levels. In FecL(L) carrier ewes only, B4GALNT2 transferase activity was localized
      in granulosa cells and specifically glycosylated proteins were detected in
      granulosa cell extracts and follicular fluids. The identification of these
      glycoproteins by mass spectrometry revealed at least 10 proteins, including
      inhibin alpha and betaA subunits, as potential targets of B4GALNT2 activity.
      Specific ovarian protein glycosylation by B4GALNT2 is proposed as a new mechanism
      of ovulation rate regulation in sheep, and could contribute to open new fields of
      investigation to understand female infertility pathogenesis. 

PMID- 24086151
TI  - Widespread dysregulation of peptide hormone release in mice lacking adaptor
      protein AP-3.
AB  - The regulated secretion of peptide hormones, neural peptides and many growth
      factors depends on their sorting into large dense core vesicles (LDCVs) capable
      of regulated exocytosis. LDCVs form at the trans-Golgi network, but the
      mechanisms that sort proteins to this regulated secretory pathway and the
      cytosolic machinery that produces LDCVs remain poorly understood. Recently, we
      used an RNAi screen to identify a role for heterotetrameric adaptor protein AP-3
      in regulated secretion and in particular, LDCV formation. Indeed, mocha mice
      lacking AP-3 have a severe neurological and behavioral phenotype, but this has
      been attributed to a role for AP-3 in the endolysosomal rather than biosynthetic
      pathway. We therefore used mocha mice to determine whether loss of AP-3 also
      dysregulates peptide release in vivo. We find that adrenal chromaffin cells from
      mocha animals show increased constitutive exocytosis of both soluble cargo and
      LDCV membrane proteins, reducing the response to stimulation. We also observe
      increased basal release of both insulin and glucagon from pancreatic islet cells
      of mocha mice, suggesting a global disturbance in the release of peptide
      hormones. AP-3 exists as both ubiquitous and neuronal isoforms, but the analysis
      of mice lacking each of these isoforms individually and together shows that loss
      of both is required to reproduce the effect of the mocha mutation on the
      regulated pathway. In addition, we show that loss of the related adaptor protein
      AP-1 has a similar effect on regulated secretion but exacerbates the effect of AP
      3 RNAi, suggesting distinct roles for the two adaptors in the regulated secretory
      pathway. 

PMID- 24086152
TI  - Whole-exome sequencing reveals a rapid change in the frequency of rare functional
      variants in a founding population of humans.
AB  - Whole-exome or gene targeted resequencing in hundreds to thousands of individuals
      has shown that the majority of genetic variants are at low frequency in human
      populations. Rare variants are enriched for functional mutations and are expected
      to explain an important fraction of the genetic etiology of human disease,
      therefore having a potential medical interest. In this work, we analyze the whole
      exome sequences of French-Canadian individuals, a founder population with a
      unique demographic history that includes an original population bottleneck less
      than 20 generations ago, followed by a demographic explosion, and the whole
      exomes of French individuals sampled from France. We show that in less than 20
      generations of genetic isolation from the French population, the genetic pool of
      French-Canadians shows reduced levels of diversity, higher homozygosity, and an
      excess of rare variants with low variant sharing with Europeans. Furthermore, the
      French-Canadian population contains a larger proportion of putatively damaging
      functional variants, which could partially explain the increased incidence of
      genetic disease in the province. Our results highlight the impact of population
      demography on genetic fitness and the contribution of rare variants to the human
      genetic variation landscape, emphasizing the need for deep cataloguing of genetic
      variants by resequencing worldwide human populations in order to truly assess
      disease risk. 

PMID- 24086153
TI  - Guanine holes are prominent targets for mutation in cancer and inherited disease.
AB  - Single base substitutions constitute the most frequent type of human gene
      mutation and are a leading cause of cancer and inherited disease. These
      alterations occur non-randomly in DNA, being strongly influenced by the local
      nucleotide sequence context. However, the molecular mechanisms underlying such
      sequence context-dependent mutagenesis are not fully understood. Using
      bioinformatics, computational and molecular modeling analyses, we have determined
      the frequencies of mutation at G * C bp in the context of all 64 5'-NGNN-3'
      motifs that contain the mutation at the second position. Twenty-four datasets
      were employed, comprising >530,000 somatic single base substitutions from 21
      cancer genomes, >77,000 germline single-base substitutions causing or associated
      with human inherited disease and 16.7 million benign germline single-nucleotide
      variants. In several cancer types, the number of mutated motifs correlated both
      with the free energies of base stacking and the energies required for abstracting
      an electron from the target guanines (ionization potentials). Similar
      correlations were also evident for the pathological missense and nonsense
      germline mutations, but only when the target guanines were located on the non
      transcribed DNA strand. Likewise, pathogenic splicing mutations predominantly
      affected positions in which a purine was located on the non-transcribed DNA
      strand. Novel candidate driver mutations and tissue-specific mutational patterns
      were also identified in the cancer datasets. We conclude that electron transfer
      reactions within the DNA molecule contribute to sequence context-dependent
      mutagenesis, involving both somatic driver and passenger mutations in cancer, as
      well as germline alterations causing or associated with inherited disease.

PMID- 24086154
TI  - Natural genetic transformation generates a population of merodiploids in
      Streptococcus pneumoniae.
AB  - Partial duplication of genetic material is prevalent in eukaryotes and provides
      potential for evolution of new traits. Prokaryotes, which are generally haploid
      in nature, can evolve new genes by partial chromosome duplication, known as
      merodiploidy. Little is known about merodiploid formation during genetic exchange
      processes, although merodiploids have been serendipitously observed in early
      studies of bacterial transformation. Natural bacterial transformation involves
      internalization of exogenous donor DNA and its subsequent integration into the
      recipient genome by homology. It contributes to the remarkable plasticity of the
      human pathogen Streptococcus pneumoniae through intra and interspecies genetic
      exchange. We report that lethal cassette transformation produced merodiploids
      possessing both intact and cassette-inactivated copies of the essential target
      gene, bordered by repeats (R) corresponding to incomplete copies of IS861. We
      show that merodiploidy is transiently stimulated by transformation, and only
      requires uptake of a ~3-kb DNA fragment partly repeated in the chromosome. We
      propose and validate a model for merodiploid formation, providing evidence that
      tandem-duplication (TD) formation involves unequal crossing-over resulting from
      alternative pairing and interchromatid integration of R. This unequal crossing
      over produces a chromosome dimer, resolution of which generates a chromosome with
      the TD and an abortive chromosome lacking the duplicated region. We document
      occurrence of TDs ranging from ~100 to ~900 kb in size at various chromosomal
      locations, including by self-transformation (transformation with recipient
      chromosomal DNA). We show that self-transformation produces a population
      containing many different merodiploid cells. Merodiploidy provides opportunities
      for evolution of new genetic traits via alteration of duplicated genes,
      unrestricted by functional selective pressure. Transient stimulation of a varied
      population of merodiploids by transformation, which can be triggered by stresses
      such as antibiotic treatment in S. pneumoniae, reinforces the plasticity
      potential of this bacterium and transformable species generally.

PMID- 24086155
TI  - Ago1 Interacts with RNA polymerase II and binds to the promoters of actively
      transcribed genes in human cancer cells.
AB  - Argonaute proteins are often credited for their cytoplasmic activities in which
      they function as central mediators of the RNAi platform and microRNA (miRNA)
      mediated processes. They also facilitate heterochromatin formation and
      establishment of repressive epigenetic marks in the nucleus of fission yeast and
      plants. However, the nuclear functions of Ago proteins in mammalian cells remain
      elusive. In the present study, we combine ChIP-seq (chromatin immunoprecipitation
      coupled with massively parallel sequencing) with biochemical assays to show that
      nuclear Ago1 directly interacts with RNA Polymerase II and is widely associated
      with chromosomal loci throughout the genome with preferential enrichment in
      promoters of transcriptionally active genes. Additional analyses show that
      nuclear Ago1 regulates the expression of Ago1-bound genes that are implicated in
      oncogenic pathways including cell cycle progression, growth, and survival. Our
      findings reveal the first landscape of human Ago1-chromosomal interactions, which
      may play a role in the oncogenic transcriptional program of cancer cells. 

PMID- 24086156
TI  - In vivo analysis of Lrig genes reveals redundant and independent functions in the
      inner ear.
AB  - Lrig proteins are conserved transmembrane proteins that modulate a variety of
      signaling pathways from worm to humans. In mammals, there are three family
      members - Lrig1, Lrig2, and Lrig3--that are defined by closely related
      extracellular domains with a similar arrangement of leucine rich repeats and
      immunoglobulin domains. However, the intracellular domains show little homology.
      Lrig1 inhibits EGF signaling through internalization and degradation of ErbB
      receptors. Although Lrig3 can also bind ErbB receptors in vitro, it is unclear
      whether Lrig2 and Lrig3 exhibit similar functions to Lrig1. To gain insights into
      Lrig gene functions in vivo, we compared the expression and function of the Lrigs
      in the inner ear, which offers a sensitive system for detecting effects on
      morphogenesis and function. We find that all three family members are expressed
      in the inner ear throughout development, with Lrig1 and Lrig3 restricted to
      subsets of cells and Lrig2 expressed more broadly. Lrig1 and Lrig3 overlap
      prominently in the developing vestibular apparatus and simultaneous removal of
      both genes disrupts inner ear morphogenesis. This suggests that these two family
      members act redundantly in the otic epithelium. In contrast, although Lrig1 and
      Lrig2 are frequently co-expressed, Lrig1(-/-);Lrig2(-/-) double mutant ears show
      no enhanced structural abnormalities. At later stages, Lrig1 expression is
      sustained in non-sensory tissues, whereas Lrig2 levels are enhanced in neurons
      and sensory epithelia. Consistent with these distinct expression patterns, Lrig1
      and Lrig2 mutant mice exhibit different forms of impaired auditory
      responsiveness. Notably, Lrig1(-/-);Lrig2(-/-) double mutant mice display
      vestibular deficits and suffer from a more severe auditory defect that is
      accompanied by a cochlear innervation phenotype not present in single mutants.
      Thus, Lrig genes appear to act both redundantly and independently, with Lrig2
      emerging as the most functionally distinct family member.

PMID- 24086157
TI  - Manipulating or superseding host recombination functions: a dilemma that shapes
      phage evolvability.
AB  - Phages, like many parasites, tend to have small genomes and may encode autonomous
      functions or manipulate those of their hosts'. Recombination functions are
      essential for phage replication and diversification. They are also nearly
      ubiquitous in bacteria. The E. coli genome encodes many copies of an octamer
      (Chi) motif that upon recognition by RecBCD favors repair of double strand breaks
      by homologous recombination. This might allow self from non-self discrimination
      because RecBCD degrades DNA lacking Chi. Bacteriophage Lambda, an E. coli
      parasite, lacks Chi motifs, but escapes degradation by inhibiting RecBCD and
      encoding its own autonomous recombination machinery. We found that only half of
      275 lambdoid genomes encode recombinases, the remaining relying on the host's
      machinery. Unexpectedly, we found that some lambdoid phages contain extremely
      high numbers of Chi motifs concentrated between the phage origin of replication
      and the packaging site. This suggests a tight association between replication,
      packaging and RecBCD-mediated recombination in these phages. Indeed, phages
      lacking recombinases strongly over-represent Chi motifs. Conversely, phages
      encoding recombinases and inhibiting host recombination machinery select for the
      absence of Chi motifs. Host and phage recombinases use different mechanisms and
      the latter are more tolerant to sequence divergence. Accordingly, we show that
      phages encoding their own recombination machinery have more mosaic genomes
      resulting from recent recombination events and have more diverse gene
      repertoires, i.e. larger pan genomes. We discuss the costs and benefits of
      superseding or manipulating host recombination functions and how this decision
      shapes phage genome structure and evolvability. 

PMID- 24086158
TI  - Evidence is evidence: an interview with Mary-Claire King. Interviewed by Jane
      Gitschier.

PMID- 24086159
TI  - Nucleosome assembly proteins get SET to defeat the guardian of chromosome
      cohesion.

PMID- 24086160
TI  - Binding of NF-kappaB to nucleosomes: effect of translational positioning,
      nucleosome remodeling and linker histone H1.
AB  - NF-kappaB is a key transcription factor regulating the expression of inflammatory
      responsive genes. How NF-kappaB binds to naked DNA templates is well documented,
      but how it interacts with chromatin is far from being clear. Here we used a
      combination of UV laser footprinting, hydroxyl footprinting and electrophoretic
      mobility shift assay to investigate the binding of NF-kappaB to nucleosomal
      templates. We show that NF-kappaB p50 homodimer is able to bind to its
      recognition sequence, when it is localized at the edge of the core particle, but
      not when the recognition sequence is at the interior of the nucleosome.
      Remodeling of the nucleosome by the chromatin remodeling machine RSC was not
      sufficient to allow binding of NF-kappaB to its recognition sequence located in
      the vicinity of the nucleosome dyad, but RSC-induced histone octamer sliding
      allowed clearly detectable binding of NF-kappaB with the slid particle.
      Importantly, nucleosome dilution-driven removal of H2A-H2B dimer led to complete
      accessibility of the site located close to the dyad to NF-kappaB. Finally, we
      found that NF-kappaB was able to displace histone H1 and prevent its binding to
      nucleosome. These data provide important insight on the role of chromatin
      structure in the regulation of transcription of NF-kappaB dependent genes. 

PMID- 24086161
TI  - PKA controls calcium influx into motor neurons during a rhythmic behavior.
AB  - Cyclic adenosine monophosphate (cAMP) has been implicated in the execution of
      diverse rhythmic behaviors, but how cAMP functions in neurons to generate
      behavioral outputs remains unclear. During the defecation motor program in C.
      elegans, a peptide released from the pacemaker (the intestine) rhythmically
      excites the GABAergic neurons that control enteric muscle contractions by
      activating a G protein-coupled receptor (GPCR) signaling pathway that is
      dependent on cAMP. Here, we show that the C. elegans PKA catalytic subunit, KIN
      1, is the sole cAMP target in this pathway and that PKA is essential for enteric
      muscle contractions. Genetic analysis using cell-specific expression of dominant
      negative or constitutively active PKA transgenes reveals that knockdown of PKA
      activity in the GABAergic neurons blocks enteric muscle contractions, whereas
      constitutive PKA activation restores enteric muscle contractions to mutants
      defective in the peptidergic signaling pathway. Using real-time, in vivo calcium
      imaging, we find that PKA activity in the GABAergic neurons is essential for the
      generation of synaptic calcium transients that drive GABA release. In addition,
      constitutively active PKA increases the duration of calcium transients and causes
      ectopic calcium transients that can trigger out-of-phase enteric muscle
      contractions. Finally, we show that the voltage-gated calcium channels UNC-2 and
      EGL-19, but not CCA-1 function downstream of PKA to promote enteric muscle
      contractions and rhythmic calcium influx in the GABAergic neurons. Thus, our
      results suggest that PKA activates neurons during a rhythmic behavior by
      promoting presynaptic calcium influx through specific voltage-gated calcium
      channels. 

PMID- 24086162
TI  - The molecular chaperone Hsp90 is required for cell cycle exit in Drosophila
      melanogaster.
AB  - The coordination of cell proliferation and differentiation is crucial for proper
      development. In particular, robust mechanisms exist to ensure that cells
      permanently exit the cell cycle upon terminal differentiation, and these include
      restraining the activities of both the E2F/DP transcription factor and Cyclin/Cdk
      kinases. However, the full complement of mechanisms necessary to restrain E2F/DP
      and Cyclin/Cdk activities in differentiating cells are not known. Here, we have
      performed a genetic screen in Drosophila melanogaster, designed to identify genes
      required for cell cycle exit. This screen utilized a PCNA-miniwhite(+) reporter
      that is highly E2F-responsive and results in a darker red eye color when crossed
      into genetic backgrounds that delay cell cycle exit. Mutation of Hsp83, the
      Drosophila homolog of mammalian Hsp90, results in increased E2F-dependent
      transcription and ectopic cell proliferation in pupal tissues at a time when
      neighboring wild-type cells are postmitotic. Further, these Hsp83 mutant cells
      have increased Cyclin/Cdk activity and accumulate proteins normally targeted for
      proteolysis by the anaphase-promoting complex/cyclosome (APC/C), suggesting that
      APC/C function is inhibited. Indeed, reducing the gene dosage of an inhibitor of
      Cdh1/Fzr, an activating subunit of the APC/C that is required for timely cell
      cycle exit, can genetically suppress the Hsp83 cell cycle exit phenotype. Based
      on these data, we propose that Cdh1/Fzr is a client protein of Hsp83. Our results
      reveal that Hsp83 plays a heretofore unappreciated role in promoting APC/C
      function during cell cycle exit and suggest a mechanism by which Hsp90 inhibition
      could promote genomic instability and carcinogenesis. 

PMID- 24086163
TI  - Whole genome sequencing identifies a deletion in protein phosphatase 2A that
      affects its stability and localization in Chlamydomonas reinhardtii.
AB  - Whole genome sequencing is a powerful tool in the discovery of single nucleotide
      polymorphisms (SNPs) and small insertions/deletions (indels) among mutant
      strains, which simplifies forward genetics approaches. However, identification of
      the causative mutation among a large number of non-causative SNPs in a mutant
      strain remains a big challenge. In the unicellular biflagellate green alga
      Chlamydomonas reinhardtii, we generated a SNP/indel library that contains over 2
      million polymorphisms from four wild-type strains, one highly polymorphic strain
      that is frequently used in meiotic mapping, ten mutant strains that have
      flagellar assembly or motility defects, and one mutant strain, imp3, which has a
      mating defect. A comparison of polymorphisms in the imp3 strain and the other 15
      strains allowed us to identify a deletion of the last three amino acids,
      Y313F314L315, in a protein phosphatase 2A catalytic subunit (PP2A3) in the imp3
      strain. Introduction of a wild-type HA-tagged PP2A3 rescues the mutant phenotype,
      but mutant HA-PP2A3 at Y313 or L315 fail to rescue. Our immunoprecipitation
      results indicate that the Y313, L315, or YFLDelta mutations do not affect the
      binding of PP2A3 to the scaffold subunit, PP2A-2r. In contrast, the Y313, L315,
      or YFLDelta mutations affect both the stability and the localization of PP2A3.
      The PP2A3 protein is less abundant in these mutants and fails to accumulate in
      the basal body area as observed in transformants with either wild-type HA-PP2A3
      or a HA-PP2A3 with a V310T change. The accumulation of HA-PP2A3 in the basal body
      region disappears in mated dikaryons, which suggests that the localization of
      PP2A3 may be essential to the mating process. Overall, our results demonstrate
      that the terminal YFL tail of PP2A3 is important in the regulation on
      Chlamydomonas mating. 

PMID- 24086164
TI  - Dealing with the evolutionary downside of CRISPR immunity: bacteria and
      beneficial plasmids.
AB  - The immune systems that protect organisms from infectious agents invariably have
      a cost for the host. In bacteria and archaea CRISPR-Cas loci can serve as
      adaptive immune systems that protect these microbes from infectiously transmitted
      DNAs. When those DNAs are borne by lytic viruses (phages), this protection can
      provide a considerable advantage. CRISPR-Cas immunity can also prevent cells from
      acquiring plasmids and free DNA bearing genes that increase their fitness. Here,
      we use a combination of experiments and mathematical-computer simulation models
      to explore this downside of CRISPR-Cas immunity and its implications for the
      maintenance of CRISPR-Cas loci in microbial populations. We analyzed the
      conjugational transfer of the staphylococcal plasmid pG0400 into Staphylococcus
      epidermidis RP62a recipients that bear a CRISPR-Cas locus targeting this plasmid.
      Contrary to what is anticipated for lytic phages, which evade CRISPR by mutations
      in the target region, the evasion of CRISPR immunity by plasmids occurs at the
      level of the host through loss of functional CRISPR-Cas immunity. The results of
      our experiments and models indicate that more than 10(-4) of the cells in CRISPR
      Cas positive populations are defective or deleted for the CRISPR-Cas region and
      thereby able to receive and carry the plasmid. Most intriguingly, the loss of
      CRISPR function even by large deletions can have little or no fitness cost in
      vitro. These theoretical and experimental results can account for the
      considerable variation in the existence, number and function of CRISPR-Cas loci
      within and between bacterial species. We postulate that as a consequence of the
      opposing positive and negative selection for immunity, CRISPR-Cas systems are in
      a continuous state of flux. They are lost when they bear immunity to laterally
      transferred beneficial genes, re-acquired by horizontal gene transfer, and ascend
      in environments where phage are a major source of mortality. 

PMID- 24086165
TI  - The Compass-like locus, exclusive to the Ambulacrarians, encodes a chromatin
      insulator binding protein in the sea urchin embryo.
AB  - Chromatin insulators are eukaryotic genome elements that upon binding of specific
      proteins display barrier and/or enhancer-blocking activity. Although several
      insulators have been described throughout various metazoans, much less is known
      about proteins that mediate their functions. This article deals with the
      identification and functional characterization in Paracentrotus lividus of
      COMPASS-like (CMPl), a novel echinoderm insulator binding protein. Phylogenetic
      analysis shows that the CMPl factor, encoded by the alternative spliced Cmp/Cmpl
      transcript, is the founder of a novel ambulacrarian-specific family of
      Homeodomain proteins containing the Compass domain. Specific association of CMPl
      with the boxB cis-element of the sns5 chromatin insulator is demonstrated by
      using a yeast one-hybrid system, and further corroborated by ChIP-qPCR and trans
      activation assays in developing sea urchin embryos. The sns5 insulator lies
      within the early histone gene cluster, basically between the H2A enhancer and H1
      promoter. To assess the functional role of CMPl within this locus, we challenged
      the activity of CMPl by two distinct experimental strategies. First we expressed
      in the developing embryo a chimeric protein, containing the DNA-binding domain of
      CMPl, which efficiently compete with the endogenous CMPl for the binding to the
      boxB sequence. Second, to titrate the embryonic CMPl protein, we microinjected an
      affinity-purified CMPl antibody. In both the experimental assays we congruently
      observed the loss of the enhancer-blocking function of sns5, as indicated by the
      specific increase of the H1 expression level. Furthermore, microinjection of the
      CMPl antiserum in combination with a synthetic mRNA encoding a forced repressor
      of the H2A enhancer-bound MBF1 factor restores the normal H1 mRNA abundance.
      Altogether, these results strongly support the conclusion that the recruitment of
      CMPl on sns5 is required for buffering the H1 promoter from the H2A enhancer
      activity, and this, in turn, accounts for the different level of accumulation of
      early linker and nucleosomal transcripts. 

PMID- 24086166
TI  - A critical role for PDGFRalpha signaling in medial nasal process development.
AB  - The primitive face is composed of neural crest cell (NCC) derived prominences.
      The medial nasal processes (MNP) give rise to the upper lip and vomeronasal
      organ, and are essential for normal craniofacial development, but the mechanism
      of MNP development remains largely unknown. PDGFRalpha signaling is known to be
      critical for NCC development and craniofacial morphogenesis. In this study, we
      show that PDGFRalpha is required for MNP development by maintaining the migration
      of progenitor neural crest cells (NCCs) and the proliferation of MNP cells.
      Further investigations reveal that PI3K/Akt and Rac1 signaling mediate PDGFRalpha
      function during MNP development. We thus establish PDGFRalpha as a novel
      regulator of MNP development and elucidate the roles of its downstream signaling
      pathways at cellular and molecular levels. 

PMID- 24086167
TI  - Pathogenesis of RON receptor tyrosine kinase in cancer cells: activation
      mechanism, functional crosstalk, and signaling addiction.
AB  - The RON receptor tyrosine kinase, a member of the MET proto-oncogene family, is a
      pathogenic factor implicated in tumor malignancy. Specifically, aberrations in
      RON signaling result in increased cancer cell growth, survival, invasion,
      angiogenesis, and drug resistance. Biochemical events such as ligand binding,
      receptor overexpression, generation of structure-defected variants, and point
      mutations in the kinase domain contribute to RON signaling activation. Recently,
      functional crosstalk between RON and signaling proteins such as MET and EFGR has
      emerged as an additional mechanism for RON activation, which is critical for
      tumorigenic development. The RON signaling crosstalk acts either as a regulatory
      feedback loop that strengthens or enhances tumorigenic phenotype of cancer cells
      or serves as a signaling compensatory pathway providing a growth/survival
      advantage for cancer cells to escape targeted therapy. Moreover, viral
      oncoproteins derived from Friend leukemia or Epstein-Barr viruses interact with
      RON to drive viral oncogenesis. In cancer cells, RON signaling is integrated into
      cellular signaling network essential for cancer cell growth and survival. These
      activities provide the molecular basis of targeting RON for cancer treatment. In
      this review, we will discuss recent data that uncover the mechanisms of RON
      activation in cancer cells, review evidence of RON signaling crosstalk relevant
      to cancer malignancy, and emphasize the significance of the RON signaling
      addiction by cancer cells for tumor therapy. Understanding aberrant RON signaling
      will not only provide insight into the mechanisms of tumor pathogenesis, but also
      lead to the development of novel strategies for molecularly targeted cancer
      treatment. 

PMID- 24086168
TI  - Goal-directed therapy in intraoperative fluid and hemodynamic management.
AB  - Intraoperative fluid management is pivotal to the outcome and success of surgery,
      especially in high-risk procedures. Empirical formula and invasive static
      monitoring have been traditionally used to guide intraoperative fluid management
      and assess volume status. With the awareness of the potential complications of
      invasive procedures and the poor reliability of these methods as indicators of
      volume status, we present a case scenario of a patient who underwent major
      abdominal surgery as an example to discuss how the use of minimally invasive
      dynamic monitoring may guide intraoperative fluid therapy. 

PMID- 24086169
TI  - Unbalanced omega-6/omega-3 ratio in red meat products in China.
AB  - Dietary meats play a crucial role in human health. The objective of this survey
      was to determine the fatty acid content and omega-6/omega-3 polyunsaturated fatty
      acids (n-6/n-3 PUFA) ratio of fresh red meat (beef and pork) from four cities
      (Shanghai, Nanjing, Yinchuan and Hohhot) in China. The results showed that the n
      6/n-3 PUFA ratio from all the samples ranged from 6 to 23. The total n-6 PUFA
      concentrations ranged from 290.54 mg/100 g in beef from Nanjing to 1601.48 mg/100
      g in pork from Hohhot, whereas the total concentrations of n-3 PUFA ranged from
      46.34 mg/100 g in beef from Nanjing to 96.03 mg/100 g in pork from Nanjing. The
      results indicated that the n-6/n-3 ratio in the red meat from all four regions is
      unbalanced and is much higher than that (< 5:1) recommended by the WHO/FAO. The
      total amount of n-3 PUFA was far lower than the required daily dose. Therefore,
      potential solutions to increase the n-3 PUFA content in meat products or to
      provide alternative source of n-3 PUFA should be explored. 

PMID- 24086170
TI  - Risk factors of type 2 diabetes in population of Jammu and Kashmir, India.
AB  - We sought to identify risk factors for type 2 diabetes (T2D) in Jammu and Kashmir
      populations, India. A total of 424 diabetic and 226 non-diabetic subjects from
      Jammu, and 161 diabetic and 100 non-diabetic subjects from Kashmir were screened
      for various parameters including fasting blood glucose level, 2 hour glucose
      level, urea, creatinine, triglycerides, total cholesterol, high-density
      lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C),
      very low-density lipoprotein (VLDL-C), uric acid, systolic and diastolic blood
      pressure level. We found that subjects aged 40-49 years had the highest rate of
      diabetes, with family income playing not much of a role. Kashmiri migrants or
      populations with rapid cultural, environmental, social or lifestyle change along
      with reduced physical activity, obesity and unhealthy lifestyle (smoking and
      alcohol consumption) were found to have higher rates of diabetes. High blood
      glucose, triglycerides and low HDL-C levels were found to be contributing to
      disease outcome. High blood pressure also contributed to a higher risk of
      developing T2D. Our study supports earlier reports confirming the contribution of
      comfortable life style, Western dietary habits and rapid life style change along
      with many other factors to the prevalence of diabetes. This may contribute to the
      epidemic proportion of diabetes in Jammu and Kashmir. Early diagnosis and routine
      screening for undiagnosed diabetes in obese subjects and subjects with parental
      diabetes history is expected to decrease the burden of chronic diabetic
      complications worldwide. 

PMID- 24086172
TI  - Martentoxin, a large-conductance Ca(2+)-activated K(+) channel inhibitor,
      attenuated TNF-alpha-induced nitric oxide release by human umbilical vein
      endothelial cells.
AB  - Martentoxin, a 4,046 Da polypeptide toxin purified from the venom of the scorpion
      Buthus martensii Karsch, has been demonstrated to block large-conductance Ca(2+)
      activated K(+) (BKCa) channels; however, its biological roles are still largely
      unknown. In the present study, we investigated the pharmacological effects of
      martentoxin on regulating the production of nitric oxide induced by TNF-alpha in
      human umbilical vein endothelial cells (HUVECs). We found that, 1, 10 and 100
      umol/L martentoxin decreased nitric oxide production by HUVECs exposed to 10
      ng/mL TNF for 6, 12 and 24 hours. We further demonstrated that martentoxin
      inhibited the activity of iNOS and retarded the down-regulation of eNOS mRNA
      induced by TNF-alpha. Therefore, martentoxin could be a potential therapeutic
      agent for vascular diseases. 

PMID- 24086171
TI  - Psychological status and diabetes-related distress of Chinese type 1 diabetes
      patients in Jiangsu province, China.
AB  - We sought to assess the psychological status and diabetes-related distress of
      Chinese type 1 diabetes patients in Jiangsu province, China. According to the
      World Health Organization criteria, 42 patients with type 1 diabetes were
      enrolled in the study and assessed with the Self-Rating Anxiety Scale (SAS), Self
      Rating Depression Scale (SDS) and Diabetes Distress Scale (DDS). All data were
      tabulated and statistical analyses were performed. The study summarized cases of
      42 patients with type 1 diabetes, including 17 males and 25 females with a mean
      age of 23+/-12 years and a mean duration of diabetes of 7+/-6 years. Compared to
      the Chinese normative data, the SAS standard score was significantly higher,
      whereas SDS standard score had no statistical significance. The SAS standard
      score was most highly correlated with diabetes duration (gamma = 0.547, P =
      0.011). Additionally, 19.5% of the patients had moderate or even severe diabetes
      related distress and 21.4% had moderate or even severe emotional burden while
      26.2% had regimen-related distress. Multiple stepwise regression analysis showed
      that the mean correlation between DDS and the four domains was high, particularly
      the emotional burden domain (estimated beta = 0.363, P < 0.001) and regimen
      related distress domain (estimated beta = 0.356, P < 0.001). The correlation
      between SAS and DDS was positive (estimated beta = 0.039, P = 0.027). In
      conclusion, the results showed the importance of psychological aspects in Chinese
      individuals with type 1 diabetes. Screening and treatment of psychological
      aspects may result in better adherence and increased quality of life for patients
      with diabetes. 

PMID- 24086173
TI  - Extraction and RP-HPLC determination of taxol in rat plasma, cell culture and
      quality control samples.
AB  - A rapid, sensitive, selective and validated reverse phase high-performance liquid
      chromatography (RP-HPLC) method for the estimation of paclitaxel in micro-sample
      of rat plasma and in culture of cancer cells was performed in this study. The
      mobile phase consisted of an optimized mixture of methanol:water: trifluroacetic
      acid (80: 20: 0.1, v/v/v). Column elution at a flow rate of 1 mL/minute with UV
      detection at 225 nm at room temperature was used. The RP-HPLC method was
      successfully applied for the determination of paclitaxel in plasma samples and in
      culture of cancer cells with nano-quantity of estimation. The validation studies
      were performed in accordance with the International Conference on Harmonization
      (ICH) guidelines. The intra- and inter-day precision showed that the coefficients
      of variation ranged from 1.07% to 4.27% at different levels of concentrations. To
      the best of our knowledge, this study also reported for the first time the
      optimization of different solvents for effective extraction of paclitaxel wherein
      tert.-butyl methyl ether (TBME): diethyl ether (DEE) in 50: 50 v/v composition
      was found most efficient with extraction efficiency ranging between 77.99% and
      91.74% and between 76.14 and 93.66% in the plasma and cell culture, respectively.
      This proposed method was successfully applied to study the pharmacokinetics of
      paclitaxel and the influence of verapamil and all-trans retinoic acid (atRA) on
      paclitaxel pharmacokinetics in rat models. This proposed method might emerge as a
      valuable aid in the laboratory monitoring of paclitaxel in a variety of in vitro
      as well as in vivo scenarios. 

PMID- 24086174
TI  - A novel recombinant DNA vaccine encoding Mycobacterium tuberculosis ESAT-6 and FL
      protects against Mycobacterium tuberculosis challenge in mice.
AB  - Mycobacterium tuberculosis 6-kDa early secretory antigenic target (ESAT-6) is a
      dominant target antigen for cell-mediated immunity in the early phase of
      tuberculosis. The fms-like tyrosine kinase 3 ligand (FL) that induces potent
      immune response has been used as an adjuvant in vaccine development. In this
      study, a new recombinant plasmid (pIRES-epitope-peptides-FL) encoding three T
      cell epitopes of ESAT-6 and FL was constructed, and the immunogenicity of the DNA
      vaccine was assessed in C57BL/6 mice immunized with the plasmid DNA vaccine.
      Additionally, a strategy of intramuscular injection with the DNA vaccine (prime)
      and intranasal administration of the epitope peptides (boost) was employed to
      induce higher immune reaction of the mice. The results showed that mice
      vaccinated with the recombinant plasmid DNA vaccine and boosted with the peptides
      not only increased the levels of Th1 cytokines (IFN-gamma and IL-12), the number
      of IFN-gamma(+) T cells and activities of cytotoxic T lymphocytes as well as IgG,
      but also enhanced protection against Mycobacterium tuberculosis challenge. In
      conclusion, these data indicate that the novel recombinant pIRES-epitope-peptides
      FL plasmid is a useful DNA vaccine for preventing Mycobacterium tuberculosis
      infection. 

PMID- 24086175
TI  - Preparation and application of polyclonal antibodiesagainst KSHV v-cyclin.
AB  - We prepared rabbit polyclonal antibodies against Kaposi's sarcoma-associated
      herpesvirus (KSHV)-encoded v-cyclin (ORF 72) and detected the natural viral
      protein using these polyclonal antibodies. Three antigenic polypeptides of v
      cyclin were designed and synthesized. A fragment of the v-cyclin gene was cloned
      into a eukaryotic expression vector pEF-MCS-Flag-IRES/Puro to construct a
      recombinant vector, pEF v-cyclin. Then, pEF v-cyclin was transfected into 293T
      and EA.hy926 cells to obtain v-cyclin-Flag fusion proteins. Six New Zealand white
      rabbits were immunized with KLH-conjugated peptides to generate polyclonal
      antibodies against v-cyclin. The polyclonal antibodies were then characterized by
      ELISA and Western blotting assays. Finally, the polyclonal antibodies against v
      cyclin were used to detect natural viral protein expressed in BCBL-1, BC-3, and
      JSC-1 cells. The results showed that using the Flag antibody, v-cyclin-Flag
      fusion protein was detected in 293T and EA.hy926 cells transfected with pEF-v
      cyclin. Furthermore, ELISA showed that the titer of the induced polyclonal rabbit
      anti-v-cyclin antibodies was higher than 1:8,000. In Western blotting assays, the
      antibodies reacted specifically with the v-cyclin-Flag fusion protein as well as
      the natural viral protein. The recombinant expression vector pEF-v-cyclin was
      constructed successfully, and the polyclonal antibodies prepared can be used for
      various biological tests including ELISA and Western blotting assays. 

PMID- 24086176
TI  - Abscess of the caudate lobe of the liver, a rare disease with a challenging
      management: a case report.
AB  - We reported a rare case of abscess of the caudate lobe of the liver in a 60-year
      old man. We first tried computed tomography (CT) guided percutaneous drainage of
      the abscess but failed to eradicate the infection. Deterioration of the general
      condition of the patient necessitated open surgical drainage, which resulted in
      cure of the abscess. The peculiar anatomical location of caudate lobe abscess
      introduces a great challenge for the surgeon in planning the appropriate
      management and paucity of patients with caudate lobe abscess has led to lack of
      guidelines for management. The non-operative interventional radiology approach
      has become the therapeutic choice for pyogenic liver abscess, but is it
      applicable also for caudate lobe abscess? 

PMID- 24086177
TI  - Switching costs in medical education.

PMID- 24086178
TI  - Detection of Mutant Huntingtin Aggregation Conformers and Modulation of SDS
      Soluble Fibrillar Oligomers by Small Molecules.
AB  - The Huntington's disease (HD) mutation leads to a complex process of Huntingtin
      (Htt) aggregation into multimeric species that eventually form visible inclusions
      in cytoplasm, nuclei and neuronal processes. One hypothesis is that smaller,
      soluble forms of amyloid proteins confer toxic effects and contribute to early
      cell dysfunction. However, analysis of mutant Htt aggregation intermediates to
      identify conformers that may represent toxic forms of the protein and represent
      potential drug targets remains difficult. We performed a detailed analysis of
      aggregation conformers in multiple in vitro, cell and ex vivo models of HD.
      Conformation-specific antibodies were used to identify and characterize
      aggregation species, allowing assessment of multiple conformers present during
      the aggregation process. Using a series of assays together with these antibodies,
      several forms could be identified. Fibrillar oligomers, defined as having a beta
      sheet rich conformation, are observed in vitro using recombinant protein and in
      protein extracts from cells in culture or mouse brain and shown to be globular,
      soluble and non-sedimentable structures. Compounds previously described to
      modulate visible inclusion body formation and reduce toxicity in HD models were
      also tested and consistently found to alter the formation of fibrillar oligomers.
      Interestingly, these compounds did not alter the rate of visible inclusion
      formation, indicating that fibrillar oligomers are not necessarily the rate
      limiting step of inclusion body formation. Taken together, we provide insights
      into the structure and formation of mutant Htt fibrillar oligomers that are
      modulated by small molecules with protective potential in HD models. 

PMID- 24086179
TI  - Exploration of microfluidic devices based on multi-filament threads and textiles:
      A review.
AB  - In this paper, we review the recent progress in the development of low-cost
      microfluidic devices based on multifilament threads and textiles for semi
      quantitative diagnostic and environmental assays. Hydrophilic multifilament
      threads are capable of transporting aqueous and non-aqueous fluids via capillary
      action and possess desirable properties for building fluid transport pathways in
      microfluidic devices. Thread can be sewn onto various support materials to form
      fluid transport channels without the need for the patterned hydrophobic barriers
      essential for paper-based microfluidic devices. Thread can also be used to
      manufacture fabrics which can be patterned to achieve suitable hydrophilic
      hydrophobic contrast, creating hydrophilic channels which allow the control of
      fluids flow. Furthermore, well established textile patterning methods and
      combination of hydrophilic and hydrophobic threads can be applied to fabricate
      low-cost microfluidic devices that meet the low-cost and low-volume requirements.
      In this paper, we review the current limitations and shortcomings of
      multifilament thread and textile-based microfluidics, and the research efforts to
      date on the development of fluid flow control concepts and fabrication methods.
      We also present a summary of different methods for modelling the fluid capillary
      flow in microfluidic thread and textile-based systems. Finally, we summarized the
      published works of thread surface treatment methods and the potential of
      combining multifilament thread with other materials to construct devices with
      greater functionality. We believe these will be important research focuses of
      thread- and textile-based microfluidics in future. 

PMID- 24086242
TI  - Characterization of the gut-associated microbiome in inflammatory pouch
      complications following ileal pouch-anal anastomosis.
AB  - INTRODUCTION: Inflammatory complications following ileal pouch-anal anastomosis
      (IPAA) for ulcerative colitis (UC) are common and thought to arise through
      mechanisms similar to de novo onset inflammatory bowel disease. The aim of this
      study was to determine whether specific organisms in the tissue-associated
      microbiota are associated with inflammatory pouch complications. METHODS:
      Patients having previously undergone IPAA were recruited from Mount Sinai
      Hospital. Clinical and demographic information were collected and a pouchoscopy
      with biopsy of both the pouch and afferent limb was performed. Patients were
      classified based on post-surgical phenotype into four outcome groups: familial
      adenomatous polyposis controls (FAP), no pouchitis, pouchitis, and Crohn's
      disease-like (CDL). Pyrosequencing of the 16S rRNA V1-V3 hypervariable region,
      and quantitative PCR for bacteria of interest, were used to identify organisms
      present in the afferent limb and pouch. Associations with outcomes were evaluated
      using exact and non-parametric tests of significance. RESULTS: Analysis at the
      phylum level indicated that Bacteroidetes were detected significantly less
      frequently (P<0.0001) in the inflammatory outcome groups (pouchitis and CDL)
      compared to both FAP and no pouchitis. Conversely, Proteobacteria were detected
      more frequently in the inflammatory groups (P=0.01). At the genus level,
      organisms associated with outcome were detected less frequently among the
      inflammatory groups compared to those without inflammation. Several of these
      organisms, including Bacteroides (P<0.0001), Parabacteroides (P<=2.2x10(-3)),
      Blautia (P<=3.0x10(-3)) and Sutterella (P<=2.5x10(-3)), were associated with
      outcome in both the pouch and afferent limb. These associations remained
      significant even following adjustment for antibiotic use, smoking, country of
      birth and gender. Individuals with quiescent disease receiving antibiotic therapy
      displayed similar reductions in these organisms as those with active pouch
      inflammation. CONCLUSIONS: Specific genera are associated with inflammation of
      the ileal pouch, with a reduction of typically ubiquitous organisms
      characterizing the inflammatory phenotypes.

PMID- 24086243
TI  - Embedding and publishing interactive, 3-dimensional, scientific figures in
      Portable Document Format (PDF) files.
AB  - With the latest release of the S2PLOT graphics library, embedding interactive, 3
      dimensional (3-d) scientific figures in Adobe Portable Document Format (PDF)
      files is simple, and can be accomplished without commercial software. In this
      paper, we motivate the need for embedding 3-d figures in scholarly articles. We
      explain how 3-d figures can be created using the S2PLOT graphics library,
      exported to Product Representation Compact (PRC) format, and included as fully
      interactive, 3-d figures in PDF files using the movie15 LaTeX package. We present
      new examples of 3-d PDF figures, explain how they have been made, validate them,
      and comment on their advantages over traditional, static 2-dimensional (2-d)
      figures. With the judicious use of 3-d rather than 2-d figures, scientists can
      now publish, share and archive more useful, flexible and faithful representations
      of their study outcomes. The article you are reading does not have embedded 3-d
      figures. The full paper, with embedded 3-d figures, is recommended and is
      available as a supplementary download from PLoS ONE (File S2). 

PMID- 24086244
TI  - Evidence for a hydrogenosomal-type anaerobic ATP generation pathway in
      Acanthamoeba castellanii.
AB  - Diverse, distantly-related eukaryotic lineages have adapted to low-oxygen
      environments, and possess mitochondrion-related organelles that have lost the
      capacity to generate adenosine triphosphate (ATP) through oxidative
      phosphorylation. A subset of these organelles, hydrogenosomes, has acquired a set
      of characteristic ATP generation enzymes commonly found in anaerobic bacteria.
      The recipient of these enzymes could not have survived prior to their acquisition
      had it not still possessed the electron transport chain present in the ancestral
      mitochondrion. In the divergence of modern hydrogenosomes from mitochondria, a
      transitional organelle must therefore have existed that possessed both an
      electron transport chain and an anaerobic ATP generation pathway. Here, we report
      a modern analog of this organelle in the habitually aerobic opportunistic
      pathogen, Acanthamoeba castellanii. This organism possesses a complete set of
      enzymes comprising a hydrogenosome-like ATP generation pathway, each of which is
      predicted to be targeted to mitochondria. We have experimentally confirmed the
      mitochondrial localizations of key components of this pathway using tandem mass
      spectrometry. This evidence is the first supported by localization and proteome
      data of a mitochondrion possessing both an electron transport chain and
      hydrogenosome-like energy metabolism enzymes. Our work provides insight into the
      first steps that might have occurred in the course of the emergence of modern
      hydrogenosomes. 

PMID- 24086245
TI  - Prostate cancer stem cell-targeted efficacy of a new-generation taxoid, SBT-1214
      and novel polyenolic zinc-binding curcuminoid, CMC2.24.
AB  - BACKGROUND: Prostate cancer is the second leading cause of cancer death among
      men. Multiple evidence suggests that a population of tumor-initiating, or cancer
      stem cells (CSCs) is responsible for cancer development and exceptional drug
      resistance, representing a highly important therapeutic target. The present study
      evaluated CSC-specific alterations induced by new-generation taxoid SBT-1214 and
      a novel polyenolic zinc-binding curcuminoid, CMC2.24, in prostate CSCs. PRINCIPAL
      FINDINGS: The CD133(high)/CD44(high) phenotype was isolated from spontaneously
      immortalized patient-derived PPT2 cells and highly metastatic PC3MM2 cells.
      Weekly treatment of the NOD/SCID mice bearing PPT2- and PC3MM3-induced tumors
      with the SBT-1214 led to dramatic suppression of tumor growth. Four of six PPT2
      and 3 of 6 PC3MM2 tumors have shown the absence of viable cells in residual
      tumors. In vitro, SBT-1214 (100 nM-1 uM; for 72 hr) induced about 60% cell death
      in CD133(high)/CD44(+/high) cells cultured on collagen I in stem cell medium (in
      contrast, the same doses of paclitaxel increased proliferation of these cells).
      The cytotoxic effects were increased when SBT-1214 was combined with the CMC2.24.
      A stem cell-specific PCR array assay revealed that this drug combination mediated
      massive inhibition of multiple constitutively up-regulated stem cell-related
      genes, including key pluripotency transcription factors. Importantly, this drug
      combination induced expression of p21 and p53, which were absent in
      CD133(high)/CD44(high) cells. Viable cells that survived this treatment regimen
      were no longer able to induce secondary spheroids, exhibited significant
      morphological abnormalities and died in 2-5 days. CONCLUSIONS: We report here
      that the SBT-1214 alone, or in combination with CMC2.24, possesses significant
      activity against prostate CD133(high)/CD44(+/high) tumor-initiating cells. This
      drug combination efficiently inhibits expression of the majority of stem cell
      related genes and pluripotency transcription factors. In addition, it induces a
      previously absent expression of p21 and p53 ("gene wake-up"), which can
      potentially reverse drug resistance by increasing sensitivity to anti-cancer
      drugs.

PMID- 24086246
TI  - Mouse basophils reside in extracellular matrix-enriched bone marrow niches which
      control their motility.
AB  - Basophils co-express FcepsilonRIalpha and CD49b, the alpha-2 chain of integrin
      type receptor VLA-2 (alpha2beta1), which recognizes type-1 collagen as a major
      natural ligand. The physiological relevance of this integrin for interactions
      with extracellular bone marrow matrix remains unknown. Herein, we examined the
      expression of several receptors of this family by bone marrow-derived basophils
      sorted either ex-vivo or after culture with IL-3. Having established that both
      populations display CD49d, CD49e and CD49f (alpha-4, alpha-5 and alpha-6
      integrins subunits, respectively), we addressed receptor functions by measuring
      migration, adhesion, proliferation and survival after interacting with matched
      natural ligands. Type I collagen, laminin and fibronectin promoted basophil
      migration/adhesion, the former being the most effective. None of these ligands
      affected basophil viability and expansion. Interactions between basophils and
      extracellular matrix are likely to play a role in situ, as supported by confocal
      3D cell imaging of femoral bone marrow sections, which revealed basophils
      exclusively in type-1 collagen-enriched niches that contained likewise laminin
      and fibronectin. This is the first evidence for a structure/function relationship
      between basophils and extracellular matrix proteins inside the mouse bone marrow.

PMID- 24086247
TI  - Modeling of rifampicin-induced CYP3A4 activation dynamics for the prediction of
      clinical drug-drug interactions from in vitro data.
AB  - Induction of cytochrome P450 3A4 (CYP3A4) expression is often implicated in
      clinically relevant drug-drug interactions (DDI), as metabolism catalyzed by this
      enzyme is the dominant route of elimination for many drugs. Although several DDI
      models have been proposed, none have comprehensively considered the effects of
      enzyme transcription/translation dynamics on induction-based DDI. Rifampicin is a
      well-known CYP3A4 inducer, and is commonly used as a positive control for
      evaluating the CYP3A4 induction potential of test compounds. Herein, we report
      the compilation of in vitro induction data for CYP3A4 by rifampicin in human
      hepatocytes, and the transcription/translation model developed for this enzyme
      using an extended least squares method that can account for inherent inter
      individual variability. We also developed physiologically based pharmacokinetic
      (PBPK) models for the CYP3A4 inducer and CYP3A4 substrates. Finally, we
      demonstrated that rifampicin-induced DDI can be predicted with reasonable
      accuracy, and that a static model can be used to simulate DDI once the blood
      concentration of the inducer reaches a steady state following repeated dosing.
      This dynamic PBPK-based DDI model was implemented on a new multi-hierarchical
      physiology simulation platform named PhysioDesigner. 

PMID- 24086248
TI  - Molecular dynamics study of Zn(abeta) and Zn(abeta)2.
AB  - The aggregation of Abeta-peptide (Abeta) is widely considered to be the critical
      step in the pathology of Alzheimer's disease. Small, soluble Abeta oligomers have
      been shown to be more neurotoxic than large, insoluble aggregates and fibrils.
      Recent studies suggest that biometal ions, including Zn(II), may play an
      important role in the aggregation process. Experimentally determining the details
      of the binding process is complicated by the kinetic lability of zinc. To study
      the dynamic nature of the zinc-bound Abeta complexes and the potential mechanisms
      by which Zn(II) affects Abeta oligomerization we have performed atomistic
      molecular dynamics (MD) simulations of Zn(Abeta) and Zn(Abeta)2. The models were
      based on NMR data and predicted coordination environments from previous density
      functional theory calculations. When modeled as 4-coordinate covalently bound
      Zn(Abeta) n complexes (where n = 1 or 2), zinc imposes conformational changes in
      the surrounding Abeta residues. Moreover, zinc reduces the helix content and
      increases the random coil content of the full peptide. Although zinc binds at the
      N-terminus of Abeta, beta-sheet formation is observed exclusively at the C
      terminus in the Zn(Abeta) and most of the Zn(Abeta)2 complexes. Furthermore,
      initial binding to zinc promotes the formation of intra-chain salt-bridges, while
      subsequent dissociation promotes the formation of inter-chain salt-bridges. These
      results suggest that Zn-binding to Abeta accelerates the aggregation of Abeta by
      unfolding the helical structure in Abeta peptide and stabilizing the formation of
      vital salt-bridges within and between Abeta peptides. 

PMID- 24086249
TI  - Association of promoter methylation of VGF and PGP9.5 with ovarian cancer
      progression.
AB  - PURPOSE: To elucidate the role of biological and clinical impact of aberrant
      promoter hypermethylation (PH) in ovarian cancer (OC). EXPERIMENTAL DESIGN: PH of
      PGP9.5, HIC1, AIM1, APC, PAK3, MGMT, KIF1A, CCNA1, ESR1, SSBP2, GSTP1, FKBP4 and
      VGF were assessed by quantitative methylation specific PCR (QMSP) in a training
      set. We selected two genes (VGF and PGP9.5) for further QMSP analysis in a larger
      independent validation (IV) set with available clinical data. Biologic relevance
      of VGF gene was also evaluated. RESULTS: PH frequency for PGP9.5 and VGF were 85%
      (316/372) and 43% (158/366) respectively in the IV set of samples while no PH was
      observed in controls. In 372 OC cases with available follow up, PGP9.5 and VGF PH
      were correlated with better patient survival [Hazard Ratios (HR) for overall
      survival (OS) were 0.59 (95% Confidence Intervals (CI)  = 0.42-0.84, p = 0.004),
      and 0.73 (95%CI = 0.55-0.97, p = 0.028) respectively, and for disease specific
      survival (DSS) were 0.57 (95%CI 0.39-0.82, p = 0.003) and 0.72 (95%CI 0.54-0.96,
      p = 0.027). In multivariate analysis, VGF PH remained an independent prognostic
      factor for OS (HR 0.61, 95%CI 0.43-0.86, p<0.005) and DSS (HR 0.58, 95%CI 0.41
      0.83, p<0.003). Furthermore, PGP9.5 PH was significantly correlated with lower
      grade, early stage tumors, and with absence of residual disease. Forced
      expression of VGF in OC cell lines inhibited cell growth. CONCLUSIONS: Our
      results indicate that VGF and PGP9.5 PH are potential biomarkers for ovarian
      carcinoma. Confirmatory cohorts with longitudinal follow-up are required in
      future studies to define the clinical impact of VGF and PGP9.5 PH before clinical
      application.

PMID- 24086250
TI  - Crystal structures of human muscle fructose-1,6-bisphosphatase: novel quaternary
      states, enhanced AMP affinity, and allosteric signal transmission pathway.
AB  - Fructose-1,6-bisphosphatase, a key enzyme in gluconeogenesis, is subject to
      metabolic regulation. The human muscle isozyme is significantly more sensitive
      towards the allosteric inhibitor, AMP, than the liver isoform. Here we report
      crystal structures and kinetic studies for wild-type human muscle Fru-1,6-Pase,
      the AMP-bound (1.6 A), and product-bound complexes of the Q32R mutant, which was
      firstly introduced by an error in the cloning. Our high-resolution structure
      reveals for the first time that the higher sensitivity of the muscle isozyme
      towards AMP originates from an additional water-mediated, H-bonded network
      established between AMP and the binding pocket. Also present in our structures
      are a metaphosphate molecule, alternate conformations of Glu97 coordinating
      Mg(2+), and possible metal migration during catalysis. Although the individual
      subunit is similar to previously reported Fru-1,6-Pase structures, the tetrameric
      assembly of all these structures deviates from the canonical R- or T-states,
      representing novel tetrameric assemblies. Intriguingly, the concentration of AMP
      required for 50% inhibition of the Q32R mutant is increased 19-fold, and the
      cooperativity of both AMP and Mg(2+) is abolished or decreased. These structures
      demonstrate the Q32R mutation affects the conformations of both N-terminal
      residues and the dynamic loop 52-72. Also importantly, structural comparison
      indicates that this mutation in helix alpha2 is detrimental to the R-to-T
      conversion as evidenced by the absence of quaternary structural changes upon AMP
      binding, providing direct evidence for the critical role of helix alpha2 in the
      allosteric signal transduction. 

PMID- 24086251
TI  - A latent parameter node-centric model for spatial networks.
AB  - Spatial networks, in which nodes and edges are embedded in space, play a vital
      role in the study of complex systems. For example, many social networks attach
      geo-location information to each user, allowing the study of not only topological
      interactions between users, but spatial interactions as well. The defining
      property of spatial networks is that edge distances are associated with a cost,
      which may subtly influence the topology of the network. However, the cost
      function over distance is rarely known, thus developing a model of connections in
      spatial networks is a difficult task. In this paper, we introduce a novel model
      for capturing the interaction between spatial effects and network structure. Our
      approach represents a unique combination of ideas from latent variable
      statistical models and spatial network modeling. In contrast to previous work, we
      view the ability to form long/short-distance connections to be dependent on the
      individual nodes involved. For example, a node's specific surroundings (e.g.
      network structure and node density) may make it more likely to form a long
      distance link than other nodes with the same degree. To capture this information,
      we attach a latent variable to each node which represents a node's spatial reach.
      These variables are inferred from the network structure using a Markov Chain
      Monte Carlo algorithm. We experimentally evaluate our proposed model on 4
      different types of real-world spatial networks (e.g. transportation, biological,
      infrastructure, and social). We apply our model to the task of link prediction
      and achieve up to a 35% improvement over previous approaches in terms of the area
      under the ROC curve. Additionally, we show that our model is particularly helpful
      for predicting links between nodes with low degrees. In these cases, we see much
      larger improvements over previous models. 

PMID- 24086252
TI  - HIV-1 transmission during early antiretroviral therapy: evaluation of two HIV-1
      transmission events in the HPTN 052 prevention study.
AB  - In the HPTN 052 study, transmission between HIV-discordant couples was reduced by
      96% when the HIV-infected partner received suppressive antiretroviral therapy
      (ART). We examined two transmission events where the newly infected partner was
      diagnosed after the HIV-infected partner (index) initiated therapy. We evaluated
      the sequence complexity of the viral populations and antibody reactivity in the
      newly infected partner to estimate the dates of transmission to the newly
      infected partners. In both cases, transmission most likely occurred significantly
      before HIV-1 diagnosis of the newly infected partner, and either just before the
      initiation of therapy or before viral replication was adequately suppressed by
      therapy of the index. This study further strengthens the conclusion about the
      efficacy of blocking transmission by treating the infected partner of discordant
      couples. However, this study does not rule out the potential for HIV-1
      transmission to occur shortly after initiation of ART, and this should be
      recognized when antiretroviral therapy is used for HIV-1 prevention. 

PMID- 24086253
TI  - Cryptic population structuring and the role of the Isthmus of Tehuantepec as a
      gene flow barrier in the critically endangered Central American River Turtle.
AB  - The critically endangered Central American River Turtle (Dermatemys mawii) is the
      only remaining member of the Dermatemydidae family, yet little is known about its
      population structuring. In a previous study of mitochondrial (mt) DNA in the
      species, three main lineages were described. One lineage (Central) was dominant
      across most of the range, while two other lineages were restricted to Papaloapan
      (PAP; isolated by the Isthmus of Tehuantepec and the Sierra de Santa Marta) or
      the south-eastern part of the range (1D). Here we provide data from seven
      polymorphic microsatellite loci and the R35 intron to re-evaluate these findings
      using DNA from the nuclear genome. Based on a slightly expanded data set of a
      total of 253 samples from the same localities, we find that mtDNA and nuclear DNA
      markers yield a highly congruent picture of the evolutionary history and
      population structuring of D. mawii. While resolution provided by the R35 intron
      (sequenced for a subset of the samples) was very limited, the microsatellite data
      revealed pronounced population structuring. Within the Grijalva-Usumacinta
      drainage basin, however, many populations separated by more than 300 kilometers
      showed signals of high gene flow. Across the entire range, neither mitochondrial
      nor nuclear DNA show a significant isolation-by-distance pattern, but both
      genomes highlight that the D. mawii population in the Papaloapan basin is
      genetically distinctive. Further, both marker systems detect unique genomic
      signals in four individuals with mtDNA clade 1D sampled on the southeast edge of
      the Grijalva-Usumacinta basin. These individuals may represent a separate cryptic
      taxon that is likely impacted by recent admixture. 

PMID- 24086254
TI  - Biodegradation of low-density polyethylene (LDPE) by mixed culture of
      Lysinibacillus xylanilyticus and Aspergillus niger in soil.
AB  - In this study, two strains of Aspergillus sp. and Lysinibacillus sp. with
      remarkable abilities to degrade low-density polyethylene (LDPE) were isolated
      from landfill soils in Tehran using enrichment culture and screening procedures.
      The biodegradation process was performed for 126 days in soil using UV- and non
      UV-irradiated pure LDPE films without pro-oxidant additives in the presence and
      absence of mixed cultures of selected microorganisms. The process was monitored
      by measuring the microbial population, the biomass carbon, pH and respiration in
      the soil, and the mechanical properties of the films. The carbon dioxide
      measurements in the soil showed that the biodegradation in the un-inoculated
      treatments were slow and were about 7.6% and 8.6% of the mineralisation measured
      for the non-UV-irradiated and UV-irradiated LDPE, respectively, after 126 days.
      In contrast, in the presence of the selected microorganisms, biodegradation was
      much more efficient and the percentages of biodegradation were 29.5% and 15.8%
      for the UV-irradiated and non-UV-irradiated films, respectively. The percentage
      decrease in the carbonyl index was higher for the UV-irradiated LDPE when the
      biodegradation was performed in soil inoculated with the selected microorganisms.
      The percentage elongation of the films decreased during the biodegradation
      process. The Fourier transform infra-red (FT-IR), x-ray diffraction (XRD) and
      scanning electron microscopy (SEM) were used to determine structural,
      morphological and surface changes on polyethylene. These analyses showed that the
      selected microorganisms could modify and colonise both types of polyethylene.
      This study also confirmed the ability of these isolates to utilise virgin
      polyethylene without pro-oxidant additives and oxidation pretreatment, as the
      carbon source. 

PMID- 24086255
TI  - Integrative analysis of metabolomics and transcriptomics data: a unified model
      framework to identify underlying system pathways.
AB  - The abundance of high-dimensional measurements in the form of gene expression and
      mass spectroscopy calls for models to elucidate the underlying biological system.
      For widely studied organisms like yeast, it is possible to incorporate prior
      knowledge from a variety of databases, an approach used in several recent
      studies. However if such information is not available for a particular organism
      these methods fall short. In this paper we propose a statistical method that is
      applicable to a dataset consisting of Liquid Chromatography-Mass Spectroscopy (LC
      MS) and gene expression (DNA microarray) measurements from the same samples, to
      identify genes controlling the production of metabolites. Due to the high
      dimensionality of both LC-MS and DNA microarray data, dimension reduction and
      variable selection are key elements of the analysis. Our proposed approach starts
      by identifying the basis functions ("building blocks") that constitute the output
      from a mass spectrometry experiment. Subsequently, the weights of these basis
      functions are related to the observations from the corresponding gene expression
      data in order to identify which genes are associated with specific patterns seen
      in the metabolite data. The modeling framework is extremely flexible as well as
      computationally fast and can accommodate treatment effects and other variables
      related to the experimental design. We demonstrate that within the proposed
      framework, genes regulating the production of specific metabolites can be
      identified correctly unless the variation in the noise is more than twice that of
      the signal. 

PMID- 24086256
TI  - Tillage, mulch and N fertilizer affect emissions of CO2 under the rain fed
      condition.
AB  - A two year (2010-2012) study was conducted to assess the effects of different
      agronomic management practices on the emissions of CO2 from a field of non
      irrigated wheat planted on China's Loess Plateau. Management practices included
      four tillage methods i.e. T1: (chisel plow tillage), T2: (zero-tillage), T3:
      (rotary tillage) and T4: (mold board plow tillage), 2 mulch levels i.e., M0 (no
      corn residue mulch) and M1 (application of corn residue mulch) and 5 levels of N
      fertilizer (0, 80, 160, 240, 320 kg N/ha). A factorial experiment having a strip
      split-split arrangement, with tillage methods in the main plots, mulch levels in
      the sub plots and N-fertilizer levels in the sub-sub plots with three replicates,
      was used for this study. The CO2 data were recorded three times per week using a
      portable GXH-3010E1 gas analyzer. The highest CO2 emissions were recorded
      following rotary tillage, compared to the lowest emissions from the zero tillage
      planting method. The lowest emissions were recorded at the 160 kg N/ha,
      fertilizer level. Higher CO2 emissions were recorded during the cropping year
      2010-11 relative to the year 2011-12. During cropping year 2010-11, applications
      of corn residue mulch significantly increased CO2 emissions in comparison to the
      non-mulched treatments, and during the year 2011-12, equal emissions were
      recorded for both types of mulch treatments. Higher CO2 emissions were recorded
      immediately after the tillage operations. Different environmental factors, i.e.,
      rain, air temperatures, soil temperatures and soil moistures, had significant
      effects on the CO2 emissions. We conclude that conservation tillage practices,
      i.e., zero tillage, the use of corn residue mulch and optimum N fertilizer use,
      can reduce CO2 emissions, give better yields and provide environmentally friendly
      options. 

PMID- 24086257
TI  - Spatiotemporal infectious disease modeling: a BME-SIR approach.
AB  - This paper is concerned with the modeling of infectious disease spread in a
      composite space-time domain under conditions of uncertainty. We focus on
      stochastic modeling that accounts for basic mechanisms of disease distribution
      and multi-sourced in situ uncertainties. Starting from the general formulation of
      population migration dynamics and the specification of transmission and recovery
      rates, the model studies the functional formulation of the evolution of the
      fractions of susceptible-infected-recovered individuals. The suggested approach
      is capable of: a) modeling population dynamics within and across localities, b)
      integrating the disease representation (i.e. susceptible-infected-recovered
      individuals) with observation time series at different geographical locations and
      other sources of information (e.g. hard and soft data, empirical relationships,
      secondary information), and c) generating predictions of disease spread and
      associated parameters in real time, while considering model and observation
      uncertainties. Key aspects of the proposed approach are illustrated by means of
      simulations (i.e. synthetic studies), and a real-world application using hand
      foot-mouth disease (HFMD) data from China. 

PMID- 24086258
TI  - PARP-1 modulates amyloid beta peptide-induced neuronal damage.
AB  - Amyloid beta peptide (Abeta) causes neurodegeneration by several mechanisms
      including oxidative stress, which is known to induce DNA damage with the
      consequent activation of poly (ADP-ribose) polymerase (PARP-1). To elucidate the
      role of PARP-1 in the neurodegenerative process, SH-SY5Y neuroblastoma cells were
      treated with Abeta25-35 fragment in the presence or absence of MC2050, a new PARP
      1 inhibitor. Abeta25-35 induces an enhancement of PARP activity which is
      prevented by cell pre-treatment with MC2050. These data were confirmed by
      measuring PARP-1 activity in CHO cells transfected with amylod precursor protein
      and in vivo in brains specimens of TgCRND8 transgenic mice overproducing the
      amyloid peptide. Following Abeta25-35 exposure a significant increase in
      intracellular ROS was observed. These data were supported by the finding that
      Abeta25-35 induces DNA damage which in turn activates PARP-1. Challenge with
      Abeta25-35 is also able to activate NF-kB via PARP-1, as demonstrated by NF-kB
      impairment upon MC2050 treatment. Moreover, Abeta25-35 via PARP-1 induces a
      significant increase in the p53 protein level and a parallel decrease in the anti
      apoptotic Bcl-2 protein. These overall data support the hypothesis of PARP-1
      involvment in cellular responses induced by Abeta and hence a possible rationale
      for the implication of PARP-1 in neurodegeneration is discussed. 

PMID- 24086259
TI  - Nasopharyngeal carriage of pneumococci four years after community-wide
      vaccination with PCV-7 in The Gambia: long-term evaluation of a cluster
      randomized trial.
AB  - BACKGROUND: A village-randomized trial of a seven-valent pneumococcal-conjugate
      vaccine (PCV-7) conducted in rural Gambia showed a decrease of vaccine-type (VT)
      and a non-significant increase in non-vaccine-type (NVT) nasopharyngeal carriage
      of pneumococci two years after vaccination. Here, we report findings four years
      after vaccination. METHODS: PCV-7 was given to all children below 30 months of
      age enrolled in the trial and to those born during its course in all study
      villages. Villages were randomized (older children and adults) to receive PCV-7
      (wholly vaccinated villages) or serogroup-C-meningococcal-conjugate-vaccine
      (partly vaccinated villages). Cross-sectional surveys (CSS) to collect
      nasopharyngeal swabs were conducted before and at various intervals after
      vaccination. Sixteen of these randomized villages (8 wholly vaccinated and 8
      partly vaccinated) participated in a CSS conducted four years after vaccination
      started. RESULTS: Four years after vaccination, the prevalence of VT pneumococcal
      carriage was slightly higher in partly than in wholly vaccinated villages [6.4%
      versus 3.9% (p = 0.120)] compared to 24.4% in the pre-vaccination CSS (p<0.001).
      Prevalence of NVT four years after vaccination was similar between study groups
      [32.7% versus 29.8% (p = 0.392), respectively] compared to 51.1% in the pre
      vaccination CSS (p<0.001). Four years after vaccination started, lower prevalence
      of serotype 6A was detected in wholly vaccinated than in partly vaccinated
      villages (1.6% versus 3.5%, p = 0.093) whilst the prevalence of serotype 19A was
      similar between groups (2.9% versus 2.5%, p = 0.779). The most prevalent serotype
      19A clone was ST 847. The most prevalent serotype 6A clone before vaccination was
      ST3324 whilst after vaccination ST913 and ST1737 predominated. Fourteen out of 26
      STs detected among the serotype 6A isolates were new while no new 19A serotype ST
      was found. CONCLUSIONS: The decline in prevalence of VT pneumococci seen shortly
      after PCV-7 vaccination was sustained four years later with only a small
      difference between study arms. No significant serotype replacement was detected.
      TRIAL REGISTRATION: ClinicalTrials.gov ISRCTN51695599.

PMID- 24086260
TI  - Use of extraocular muscle flaps in the correction of orbital implant exposure.
AB  - PURPOSES: The study is to describe a new surgical technique for correcting large
      orbital implant exposure with extraocular muscle flaps and to propose a treatment
      algorithm for orbital implant exposure. METHODS: In a retrospective study, seven
      patients with orbital implant exposure were treated with extraocular muscle
      flaps. All data were collected from patients in Chang Gung Memorial Hospital,
      Taiwan during 2007-2012. All surgeries were performed by one surgeon (Y.J.T).
      Patient demographics, the original etiology, details of surgical procedures,
      implant types, and follow-up interval were recorded. Small exposure, defined as
      exposure area smaller than 3 mm in diameter, was treated conservatively first
      with topical lubricant and prophylactic antibiotics. Larger defects were managed
      surgically. RESULTS: Seven patients consisting of two males and five females were
      successfully treated for orbital implant exposure with extraocular muscle flaps.
      The average age was 36.4 (range, 3-55) years old. Five patients were referred
      from other hospitals. One eye was enucleated for retinoblastoma. The other six
      eyes were eviscerated, including one for endophthalmitis and five for trauma.
      Mean follow-up time of all seven patients was 19.5 (range, 2-60) months. No
      patient developed recurrence of exposure during follow-up. All patients were
      fitted with an acceptable prosthesis and had satisfactory cosmetic and functional
      results. CONCLUSIONS: The most common complication of orbital implant is
      exposure, caused by breakdown of the covering layers, leading to extrusion.
      Several methods were reported to manage the exposed implants. We report our
      experience of treating implant exposure with extraocular muscle flaps to
      establish a well-vascularized environment that supplies both the wrapping
      material and the overlying ocular surface tissue. We believe it can work as a
      good strategy to manage or to prevent orbital implant exposure.

PMID- 24086261
TI  - Association between MGMT promoter methylation and non-small cell lung cancer: a
      meta-analysis.
AB  - BACKGROUND: O(6)-methylguanine-DNA methyltransferase (MGMT) is one of most
      important DNA repair enzyme against common carcinogens such as alkylate and
      tobacco. Aberrant promoter methylation of the gene is frequently observed in non
      small cell lung cancer (NSCLC). However, the importance of epigenetic
      inactivation of the gene in NSCLC published in the literature showed
      inconsistence. We quantified the association between MGMT promoter methylation
      and NSCLC using a meta-analysis method. METHODS: We systematically reviewed
      studies of MGMT promoter methylation and NSCLC in PubMed, EMBASE, Ovid, ISI Web
      of Science, Elsevier and CNKI databases and quantified the association between
      MGMT promoter methylation and NSCLC using meta-analysis method. Odds ratio (OR)
      and corresponding 95% confidence interval (CI) were calculated to evaluate the
      strength of association. Potential sources of heterogeneity were assessed by
      subgroup analysis and meta-regression. RESULTS: A total of 18 studies from 2001
      to 2011, with 1, 160 tumor tissues and 970 controls, were involved in the meta
      analysis. The frequencies of MGMT promote methylation ranged from 1.5% to 70.0%
      (median, 26.1%) in NSCLC tissue and 0.0% to 55.0% (median, 2.4%) in non-cancerous
      control, respectively. The summary of OR was 4.43 (95% CI: 2.85, 6.89) in the
      random-effects model. With stratification by potential source of heterogeneity,
      the OR was 20.45 (95% CI: 5.83, 71.73) in heterogeneous control subgroup, while
      it was 4.16 (95% CI: 3.02, 5.72) in the autologous control subgroup. The OR was
      5.31 (95% CI: 3.00, 9.41) in MSP subgroup and 3.06 (95% CI: 1.75, 5.33) in Q-MSP
      subgroup. CONCLUSION: This meta-analysis identified a strong association between
      methylation of MGMT gene and NSCLC. Prospective studies should be required to
      confirm the results in the future.

PMID- 24086262
TI  - Area-level deprivation and overall and cause-specific mortality: 12 years'
      observation on British women and systematic review of prospective studies.
AB  - BACKGROUND: Prospective studies have suggested a negative impact of area
      deprivation on overall mortality, but its effect on cause-specific mortality and
      the mechanisms that account for this association remain unclear. We investigate
      the association of area deprivation, using Index of Multiple deprivation (IMD),
      with overall and cause-specific mortality, contextualising findings within a
      systematic review. METHODS AND FINDINGS: We used data from 4,286 women from the
      British Women's Heart Health Study (BWHHS) recruited at 1999-2001 to examine the
      association of IMD with overall and cause-specific mortality using Cox regression
      models. One standard deviation (SD) increase in the IMD score had a hazard ratio
      (HR) of 1.21 (95% CI: 1.13-1.30) for overall mortality after adjustment for age
      and lifecourse individual deprivation, which was attenuated to 1.15 (95% CI: 1.04
      1.26) after further inclusion of mediators (health behaviours, biological factors
      and use of statins and blood pressure-lowering medications). A more pronounced
      association was observed for respiratory disease and vascular deaths. The meta
      analysis, based on 20 published studies plus the BWHHS (n=21), yielded a summary
      relative risk (RR) of 1.15 (95% CI: 1.11-1.19) for area deprivation (top [least
      deprived; reference] vs. bottom tertile) with overall mortality in an age and sex
      adjusted model, which reduced to 1.06 (95% CI: 1.04-1.08) in a fully adjusted
      model. CONCLUSIONS: Health behaviours mediate the association between area
      deprivation and cause-specific mortality. Efforts to modify health behaviours may
      be more successful if they are combined with measures that tackle area
      deprivation.

PMID- 24086263
TI  - Polyalanine repeat polymorphism in RUNX2 is associated with site-specific
      fracture in post-menopausal females.
AB  - Runt related transcription factor 2 (RUNX2) is a key regulator of osteoblast
      differentiation. Several variations within the RUNX2 gene have been found to be
      associated with significant changes in BMD, which is a major risk factor for
      fracture. In this study we report that an 18 bp deletion within the polyalanine
      tract (17A>11A) of RUNX2 is significantly associated with fracture. Carriers of
      the 11A allele were found to be nearly twice as likely to have sustained
      fracture. Within the fracture category, there was a significant tendency of 11A
      carriers to present with fractures of distal radius and bones of intramembranous
      origin compared to bones of endochondral origin (p = 0.0001). In a population of
      random subjects, the 11A allele was associated with decreased levels of serum
      collagen cross links (CTx, p = 0.01), suggesting decreased bone turnover. The
      transactivation function of the 11A allele showed a minor quantitative decrease.
      Interestingly, we found no effect of the 11A allele on BMD at multiple skeletal
      sites. These findings suggest that the 11A allele is a biologically relevant
      polymorphism that influences serum CTx and confers enhanced fracture risk in a
      site-selective manner related to intramembranous bone ossification. 

PMID- 24086264
TI  - A new archosauriform (Reptilia: Diapsida) from the Manda beds (Middle Triassic)
      of southwestern Tanzania.
AB  - BACKGROUND: Archosauria and their closest relatives, the non-archosaurian
      archosauriforms, diversified in the Early and Middle Triassic, soon after the end
      Permian extinction. This diversification is poorly documented in most Lower and
      Middle Triassic rock sequences because fossils of early groups of archosauriforms
      are relatively rare compared to those of other amniotes. The early Middle
      Triassic (? late Anisian) Manda beds of southwestern Tanzania form an exception,
      with early archosaur skeletons being relatively common and preserved as
      articulated or associated specimens. The Manda archosaur assemblage is
      exceptionally diverse for the Middle Triassic. However, to date, no non
      archosaurian archosauriforms have been reported from these rocks.
      METHODOLOGY/PRINCIPAL FINDINGS: Here, we name a new taxon, Asperoris mnyama gen.
      et sp. nov., from the Manda beds and thoroughly describe the only known specimen.
      The specimen consists of a well-preserved partial skull including tooth-bearing
      elements (premaxilla, maxilla), the nasal, partial skull roof, and several
      incomplete elements. All skull elements are covered in an autapomorphic highly
      rugose sculpturing. A unique combination of character states indicates that A.
      mnyama lies just outside Archosauria as a stem archosaur within Archosauriformes,
      but more precise relationships of A. mnyama relative to other early
      archosauriform clades (e.g., Erythrosuchidae) cannot be determined currently.
      CONCLUSIONS/SIGNIFICANCE: Asperoris mnyama is the first confirmed non
      archosaurian archosauriform from the Manda beds and increases the morphological
      and taxonomic diversity of early archosauriforms known from the Middle Triassic.
      The direct association of A. mnyama with species referable to Archosauria
      demonstrates that non-archosaurian archosauriforms were present during the rise
      and early diversification of Archosauria. Non-archosaurian archosauriforms and
      archosaurs co-occur in fossil reptile assemblages across Pangaea from the late
      Early Triassic to the end of the Late Triassic.

PMID- 24086265
TI  - Conformational dissection of a viral intrinsically disordered domain involved in
      cellular transformation.
AB  - Intrinsic disorder is abundant in viral genomes and provides conformational
      plasticity to its protein products. In order to gain insight into its structure
      function relationships, we carried out a comprehensive analysis of structural
      propensities within the intrinsically disordered N-terminal domain from the human
      papillomavirus type-16 E7 oncoprotein (E7N). Two E7N segments located within the
      conserved CR1 and CR2 regions present transient alpha-helix structure. The helix
      in the CR1 region spans residues L8 to L13 and overlaps with the E2F mimic linear
      motif. The second helix, located within the highly acidic CR2 region, presents a
      pH-dependent structural transition. At neutral pH the helix spans residues P17 to
      N29, which include the retinoblastoma tumor suppressor LxCxE binding motif
      (residues 21-29), while the acidic CKII-PEST region spanning residues E33 to I38
      populates polyproline type II (PII) structure. At pH 5.0, the CR2 helix
      propagates up to residue I38 at the expense of loss of PII due to charge
      neutralization of acidic residues. Using truncated forms of HPV-16 E7, we
      confirmed that pH-induced changes in alpha-helix content are governed by the
      intrinsically disordered E7N domain. Interestingly, while at both pH the region
      encompassing the LxCxE motif adopts alpha-helical structure, the isolated 21-29
      fragment including this stretch is unable to populate an alpha-helix even at high
      TFE concentrations. Thus, the E7N domain can populate dynamic but discrete
      structural ensembles by sampling alpha-helix-coil-PII-beta-sheet structures. This
      high plasticity may modulate the exposure of linear binding motifs responsible
      for its multi-target binding properties, leading to interference with key cell
      signaling pathways and eventually to cellular transformation by the virus. 

PMID- 24086266
TI  - Hepatocyte expression of the senescence marker p21 is linked to fibrosis and an
      adverse liver-related outcome in alcohol-related liver disease.
AB  - BACKGROUND AND AIM: Alcohol-related liver disease (ALD) remains a leading cause
      of liver-related morbidity and mortality. Age, fibrosis stage, MELD score and
      continued alcohol consumption predict outcome in everyday clinical practice. In
      previous studies increased hepatocyte nuclear area and hepatocyte expression of
      p21, both markers of senescence, were associated with increased fibrosis stage
      and a poor outcome in non-alcohol-related fatty liver disease, while increased
      hepatocyte nuclear area was related to liver dysfunction in ALD cirrhosis. This
      study, therefore, investigated the pattern of hepatocyte cell cycle phase
      distribution and hepatocyte p21 expression in relation to outcome in ALD.
      METHODS: Liver sections from two cohorts were studied. The first comprised 42
      patients across the full spectrum of ALD. The second cohort comprised 77 patients
      with ALD cirrhosis. Immunohistochemistry assessed hepatocyte expression of cell
      cycle phase markers and p21. Regenerating liver (n=12) and "normal" liver
      sections (n=5) served as positive and negative controls, respectively. RESULTS:
      In the first cohort there was little cell cycle progression beyond G1/S phase and
      increased hepatocyte p21 expression (p<0.0001), which correlated independently
      with fibrosis stage (p=0.005) and an adverse liver-related outcome (p=0.03). In
      the second cohort, both hepatocyte p21 expression (p<0.001) and MELD score
      (p=0.006) were associated independently with an adverse liver-related outcome;
      this association was stronger with hepatocyte p21 expression (AUROC 0.74;
      p=0.0002) than with MELD score (AUROC 0.59; p=0.13). Further, hepatocyte p21
      expression co-localised with increased hepatic stellate cell activation.
      CONCLUSIONS: The findings are consistent with impaired cell cycle progression
      beyond the G1/S phase in ALD. The striking independent associations between
      increased hepatocyte p21 expression and both fibrosis stage and an adverse liver
      related outcome in both cohorts suggests hepatocyte senescence plays an important
      role in ALD. Measuring hepatocyte p21 expression is simple and cheap and in this
      series was a useful measure of long-term prognosis in ALD.

PMID- 24086267
TI  - Equivalent latitude computation using regions of interest (ROI).
AB  - This paper introduces a novel algorithm to compute equivalent latitude by
      applying regions of interest (ROI). The technique is illustrated using code
      written in Interactive Data Language (IDL). The ROI method is compared with the
      "piecewise-constant" method, the approach commonly used in atmospheric sciences,
      using global fields of atmospheric potential vorticity. The ROI method is
      considerably more accurate and computationally faster than the piecewise-constant
      method, and it also works well with irregular grids. Both the ROI and piecewise
      constant IDL codes for equivalent latitude are included as a useful reference for
      the research community. 

PMID- 24086268
TI  - The role of flagella in Clostridium difficile pathogenesis: comparison between a
      non-epidemic and an epidemic strain.
AB  - Clostridium difficile is a major cause of healthcare-associated infection and
      inflicts a considerable financial burden on healthcare systems worldwide. Disease
      symptoms range from self-limiting diarrhoea to fatal pseudomembranous colitis.
      Whilst C. difficile has two major virulence factors, toxin A and B, it is
      generally accepted that other virulence components of the bacterium contribute to
      disease. C. difficile colonises the gut of humans and animals and hence the
      processes of adherence and colonisation are essential for disease onset.
      Previously it has been suggested that flagella might be implicated in
      colonisation. Here we tested this hypothesis by comparing flagellated parental
      strains to strains in which flagella genes were inactivated using ClosTron
      technology. Our focus was on a UK-outbreak, PCR-ribotype 027 (B1/NAP1) strain,
      R20291. We compared the flagellated wild-type to a mutant with a paralyzed
      flagellum and also to mutants (fliC, fliD and flgE) that no longer produce
      flagella in vitro and in vivo. Our results with R20291 provide the first strong
      evidence that by disabling the motor of the flagellum, the structural components
      of the flagellum rather than active motility, is needed for adherence and
      colonisation of the intestinal epithelium during infection. Comparison to
      published data on 630Deltaerm and our own data on that strain revealed major
      differences between the strains: the R20291 flagellar mutants adhered less than
      the parental strain in vitro, whereas we saw the opposite in 630Deltaerm. We also
      showed that flagella and motility are not needed for successful colonisation in
      vivo using strain 630Deltaerm. Finally we demonstrated that in strain R20291,
      flagella do play a role in colonisation and adherence and that there are striking
      differences between C. difficile strains. The latter emphasises the overriding
      need to characterize more than just one strain before drawing general conclusions
      concerning specific mechanisms of pathogenesis. 

PMID- 24086269
TI  - Plasma proteome profiles associated with diet-induced metabolic syndrome and the
      early onset of metabolic syndrome in a pig model.
AB  - Obesity and related diabetes are important health threatening multifactorial
      metabolic diseases and it has been suggested that 25% of all diabetic patients
      are unaware of their patho-physiological condition. Biomarkers for monitoring and
      control are available, but early stage predictive biomarkers enabling prevention
      of these diseases are still lacking. We used the pig as a model to study
      metabolic disease because humans and pigs share a multitude of metabolic
      similarities. Diabetes was chemically induced and control and diabetic pigs were
      either fed a high unsaturated fat (Mediterranean) diet or a high saturated
      fat/cholesterol/sugar (cafeteria) diet. Physiological parameters related to fat
      metabolism and diabetes were measured. Diabetic pigs' plasma proteome profiles
      differed more between the two diets than control pigs plasma proteome profiles.
      The expression levels of several proteins correlated well with
      (patho)physiological parameters related to the fat metabolism (cholesterol, VLDL,
      LDL, NEFA) and diabetes (Glucose) and to the diet fed to the animals. Studying
      only the control pigs as a model for metabolic syndrome when fed the two diets
      showed correlations to the same parameters but now more focused on insulin,
      glucose and abdominal fat depot parameters. We conclude that proteomic profiles
      can be used as a biomarker to identify pigs with developing metabolic syndrome
      (prediabetes) and diabetes when fed a cafeteria diet. It could be developed into
      a potential biomarkers for the early recognition of metabolic diseases. 

PMID- 24086270
TI  - Endohyphal bacterium enhances production of indole-3-acetic acid by a foliar
      fungal endophyte.
AB  - Numerous plant pathogens, rhizosphere symbionts, and endophytic bacteria and
      yeasts produce the important phytohormone indole-3-acetic acid (IAA), often with
      profound effects on host plants. However, to date IAA production has not been
      documented among foliar endophytes -- the diverse guild of primarily filamentous
      Ascomycota that live within healthy, above-ground tissues of all plant species
      studied thus far. Recently bacteria that live within hyphae of endophytes
      (endohyphal bacteria) have been detected, but their effects have not been studied
      previously. Here we show not only that IAA is produced in vitro by a foliar
      endophyte (here identified as Pestalotiopsis aff. neglecta, Xylariales), but that
      IAA production is enhanced significantly when the endophyte hosts an endohyphal
      bacterium (here identified as Luteibacter sp., Xanthomonadales). Both the
      endophyte and the endophyte/bacterium complex appear to rely on an L-tryptophan
      dependent pathway for IAA synthesis. The bacterium can be isolated from the
      fungus when the symbiotic complex is cultivated at 36 degrees C. In pure culture
      the bacterium does not produce IAA. Culture filtrate from the endophyte-bacterium
      complex significantly enhances growth of tomato in vitro relative to controls and
      to filtrate from the endophyte alone. Together these results speak to a
      facultative symbiosis between an endophyte and endohyphal bacterium that strongly
      influences IAA production, providing a new framework in which to explore
      endophyte-plant interactions. 

PMID- 24086271
TI  - Circulating liver-specific miR-122 as a novel potential biomarker for diagnosis
      of cholestatic liver injury.
AB  - BACKGROUND: Circulating microRNA-122 (miR-122) has been increasingly reported to
      be a potential biomarker for drug-, viral-, alcohol- and chemical-induced liver
      injury. The present study was initiated to determine the potential of circulating
      miR-122 as a biomarker for cholestatic liver injury. METHODS: Both bile-duct
      ligation (BDL) mice and patients with biliary calculi were employed as
      cholestatic liver injury models, and serum miR-122 level was determined by stem
      loop real-time reverse-transcription PCR (SLqRT-PCR). All quantitative PCR values
      were normalized to those for U6 RNA and calculated with the 2(-?Ct) method.
      RESULTS: Serum miR-122 increased significantly after BDL-induced cholestatic
      injury and showed a similar time course to ALT concentrations. Compared with the
      sham controls, BDL mice had increased serum levels of miR-122 by 24.36+/-12.86,
      423.63+/-322.89, 4.43+/-2.02 and 12.23+/-8.92 folds after 1, 3, 7 and 14 days,
      respectively. Moreover, serum miR-122 level was substantially higher in patients
      with biliary calculi than that in the healthy control group. In addition,
      patients with severe liver injury showed significantly higher levels of serum miR
      122 when compared with healthy controls or patients with mild or moderate liver
      injury. Furthermore, serum miR-122 was found to show significant diagnostic value
      for biliary calculi by yielding an AUC (the areas under the receiver operating
      characteristic curve) of 0.931 with 77.4% sensitivity and 96.4% specificity in
      discriminating biliary calculi from healthy controls. CONCLUSION: Collectively,
      these data suggest that serum miR-122 has strong potential as a novel, specific
      and noninvasive biomarker for diagnosis of cholestasis-induced liver injury.

PMID- 24086272
TI  - Contribution of corticospinal tract and functional connectivity in hand motor
      impairment after stroke.
AB  - BACKGROUND: Motor outcome after stroke is associated with reorganisation of
      cortical networks and corticospinal tract (CST) integrity. However, the
      relationships between motor severity, CST damage, and functional brain
      connectivity are not well understood. Here, the main objective was to study the
      effect of CST damage on the relationship between functional motor network
      connectivity and hand motor function in two groups of stroke patients: the
      severely (n=8) and the mildly impaired (n=14). METHODS: Twenty-two carotid stroke
      patients with motor deficits were studied with magnetic resonance imaging (MRI)
      at 3 weeks, at 3 and 6 months. Healthy subjects (n=28) were scanned once. The CST
      injury was assessed by fractional anisotropy values. Functional connectivity was
      studied from a whole-hand grip task fMRI in a cortical and cerebellar motor
      network. Functional connectivity indexes were computed between these regions at
      each time point. The relationship between hand motor strength, ipsilesional CST
      damage and functional connectivity from the primary motor cortex (M1) was
      investigated using global and partial correlations. FINDINGS: In mildly impaired
      patients, cortico-cortical connectivity was disturbed at three weeks but returned
      to a normal pattern after 3 months. Cortico-cerebellar connectivity was still
      decreased at 6 months. In severely impaired patients, the cortico-cortical
      connectivity tended to return to a normal pattern, but the cortico-cerebellar
      connectivity was totally abolished during the follow-up. In the entire group of
      patients, the hand motor strength was correlated to the ipsilesional functional
      connectivity from M1. Partial correlations revealed that these associations were
      not anymore significant when the impact of CST damage was removed, except for the
      ipsilesional M1-contralateral cerebellum connectivity. CONCLUSION: Functional
      brain connectivity changes can be observed, even in severely impaired patients
      with no recovery. Upper limb function is mainly explained by the CST damage and
      by the ipsilesional cortico-cerebellar connectivity.

PMID- 24086274
TI  - Long-range correlations in stride intervals may emerge from non-chaotic walking
      dynamics.
AB  - Stride intervals of normal human walking exhibit long-range temporal
      correlations. Similar to the fractal-like behaviors observed in brain and heart
      activity, long-range correlations in walking have commonly been interpreted to
      result from chaotic dynamics and be a signature of health. Several mathematical
      models have reproduced this behavior by assuming a dominant role of neural
      central pattern generators (CPGs) and/or nonlinear biomechanics to evoke chaos.
      In this study, we show that a simple walking model without a CPG or biomechanics
      capable of chaos can reproduce long-range correlations. Stride intervals of the
      model revealed long-range correlations observed in human walking when the model
      had moderate orbital stability, which enabled the current stride to affect a
      future stride even after many steps. This provides a clear counterexample to the
      common hypothesis that a CPG and/or chaotic dynamics is required to explain the
      long-range correlations in healthy human walking. Instead, our results suggest
      that the long-range correlation may result from a combination of noise that is
      ubiquitous in biological systems and orbital stability that is essential in
      general rhythmic movements. 

PMID- 24086273
TI  - Commensal microbiota contributes to chronic endocarditis in TAX1BP1 deficient
      mice.
AB  - Tax1-binding protein 1 (Tax1bp1) negatively regulates NF-kappaB by editing the
      ubiquitylation of target molecules by its catalytic partner A20. Genetically
      engineered TAX1BP1-deficient (KO) mice develop age-dependent inflammatory
      constitutions in multiple organs manifested as valvulitis or dermatitis and
      succumb to premature death. Laser capture dissection and gene expression
      microarray analysis on the mitral valves of TAX1BP1-KO mice (8 and 16 week old)
      revealed 588 gene transcription alterations from the wild type. SAA3 (serum
      amyloid A3), CHI3L1, HP, IL1B and SPP1/OPN were induced 1,180-, 361-, 187-, 122-
      and 101-fold respectively. WIF1 (Wnt inhibitory factor 1) exhibited 11-fold
      reduction. Intense Saa3 staining and significant I-kappaBalpha reduction were
      reconfirmed and massive infiltration of inflammatory lymphocytes and edema
      formation were seen in the area. Antibiotics-induced 'germ free' status or the
      additional MyD88 deficiency significantly ameliorated TAX1BP1-KO mice's
      inflammatory lesions. These pathological conditions, as we named 'pseudo
      infective endocarditis' were boosted by the commensal microbiota who are usually
      harmless by their nature. This experimental outcome raises a novel mechanistic
      linkage between endothelial inflammation caused by the ubiquitin remodeling
      immune regulators and fatal cardiac dysfunction. 

PMID- 24086275
TI  - Contact geometry affects lesion formation in radio-frequency cardiac catheter
      ablation.
AB  - One factor which may be important for determining proper lesion creation during
      atrial ablation is catheter-endocardial contact. Little information is available
      that relates geometric contact, depth and angle, to ablation lesion formation. We
      present an electrothermal computer model of ablation that calculated lesion
      volume and temperature development over time. The Pennes bioheat equation was
      coupled to a quasistatic electrical problem to investigate the effect of catheter
      penetration depth, as well as incident catheter angle as may occur in practice.
      Biological experiments were performed to verify the modelling of electrical
      phenomena. Results show that for deeply penetrating tips, acute catheter angles
      reduced the rate of temperature buildup, allowing larger lesions to form before
      temperatures elevated excessively. It was also found that greater penetration did
      not lead to greater transmurality of lesions. We conclude that catheter contact
      angle plays a significant role in lesion formation, and the time course must be
      considered. This is clinically relevant because proper identification and
      prediction of geometric contact variables could improve ablation efficacy. 

PMID- 24086276
TI  - Mixed convection flow of nanofluid in presence of an inclined magnetic field.
AB  - This research is concerned with the mixed convection peristaltic flow of
      nanofluid in an inclined asymmetric channel. The fluid is conducting in the
      presence of inclined magnetic field. The governing equations are modelled.
      Mathematical formulation is completed through long wavelength and low Reynolds
      number approach. Numerical solution to the nonlinear analysis is made by shooting
      technique. Attention is mainly focused to the effects of Brownian motion and
      thermophoretic diffusion of nanoparticle. Results for velocity, temperature,
      concentration, pumping and trapping are obtained and analyzed in detail. 

PMID- 24086277
TI  - Normalized T1 magnetic resonance imaging for assessment of regional lung function
      in adult cystic fibrosis patients--a cross-sectional study.
AB  - BACKGROUND: Cystic fibrosis (CF) patients would benefit from a safe and effective
      tool to detect early-stage, regional lung disease to allow for early
      intervention. Magnetic Resonance Imaging (MRI) is a safe, non-invasive procedure
      capable of providing quantitative assessments of disease without ionizing
      radiation. We developed a rapid normalized T1 MRI technique to detect regional
      lung disease in early-stage CF patients. MATERIALS AND METHODS: Conventional
      multislice, pulmonary T1 relaxation time maps were obtained for 10 adult CF
      patients with normal spirometry and 5 healthy non-CF control subjects using a
      rapid Look-Locker MRI acquisition (5 seconds/imaging slice). Each lung absolute
      T1 map was separated into six regions of interest (ROI) by manually selecting
      upper, central, and lower lung regions in the left and right lungs. In order to
      reduce the effects of subject-to-subject variation, normalized T1 maps were
      calculated by dividing each pixel in the absolute T1 maps by the mean T1 time in
      the central lung region. The primary outcome was the differences in mean
      normalized T1 values in the upper lung regions between CF patients with normal
      spirometry and healthy volunteers. RESULTS: Normalized T1 (nT1) maps showed
      visibly reduced subject-to-subject variation in comparison to conventional
      absolute T1 maps for healthy volunteers. An ROI analysis showed that the
      variation in the nT1 values in all regions was <=2% of the mean. The primary
      outcome, the mean (SD) of the normalized T1 values in the upper right lung
      regions, was significantly lower in the CF subjects [.914 (.037)] compared to the
      upper right lung regions of the healthy subjects [.983 (.003)] [difference of
      .069 (95% confidence interval .032-.105); p = .001). Similar results were seen in
      the upper left lung region. CONCLUSION: Rapid normalized T1 MRI relaxometry
      obtained in 5 seconds/imaging slice may be used to detect regional early-stage
      lung disease in CF patients.

PMID- 24086278
TI  - Genome-wide analysis of selective constraints on high stability regions of mRNA
      reveals multiple compensatory mutations in Escherichia coli.
AB  - Message RNA (mRNA) carries a large number of local secondary structures, with
      structural stability to participate in the regulations of gene expression. A
      worthy question is how the local structural stability is maintained under the
      constraint that multiple selective pressures are imposed on mRNA local regions.
      Here, we performed the first genome-wide study of natural selection operating on
      high structural stability regions (HSRs) of mRNAs in Escherichia coli. We found
      that HSR tends to adjust the folded conformation to reduce the harm of mutations,
      showing a high level of mutational robustness. Moreover, guanine preference in
      HSR was observed, supporting the hypothesis that the selective constraint for
      high structural stability may partly account for the high percentage of G content
      in Escherichia coli genome. Notably, we found a substantially reduced synonymous
      substitution rate in HSRs compared with that in their adjacent regions.
      Surprisingly and interestingly, the non-key sites in HSRs, which have slight
      effect on structural stability, have synonymous substitution rate equivalent to
      background regions. To explain this result, we identified compensatory mutations
      in HSRs based on structural stability, and found that a considerable number of
      synonymous mutations occur to restore the structural stability decreased heavily
      by the mutations on key sites. Overall, these results suggest a significant role
      of local structural stability as a selective force operating on mRNA, which
      furthers our understanding of the constraints imposed on protein-coding RNAs. 

PMID- 24086279
TI  - Determinants of malaria program expenditures during elimination: case study
      evidence from select provinces in the Philippines.
AB  - ...Even though eliminating malaria from the endemic margins is a part of the
      Global Malaria Action Plan, little guidance exists on what resources are needed
      to transition from controlling malaria to eliminating it. Using Philippines as an
      example, this study aimed to (1) estimate the financial resources used by sub
      national malaria programs in different phases during elimination and (2)
      understand how different environmental and organizational factors may influence
      expenditure levels and spending proportions. The Philippines provides an
      opportunity to study variations in sub-national programs because its
      epidemiological and ecological diversity, devolved health system, and progressive
      elimination strategy all allow greater flexibility for lower-level governments to
      direct activities, but also create challenges for coordination and resource
      mobilization. Through key informant interviews and archival record retrieval in
      four selected provinces chosen based on eco-epidemiological variation,
      expenditures associated with provincial malaria programs were collected for
      selected years (mid-1990s to 2010). Results show that expenditures per person at
      risk per year decrease as programs progress from a state of controlled low
      endemic malaria to elimination to prevention of reintroduction regardless of
      whether elimination was deliberately planned. However, wide variation across
      provinces were found: expenditures were generally higher if mainly financed with
      donor grants, but were moderated by the level of economic development, the level
      of malaria transmission and receptivity, and the capacity of program staff.
      Across all provinces, strong leadership appears to be a necessary condition for
      maintaining progress and is vital in controlling outbreaks. While sampled
      provinces and years may not be representative of other sub-national malaria
      programs, these findings suggest that the marginal yearly cost declines with each
      phase during elimination. 

PMID- 24086280
TI  - Ascosphaera callicarpa, a new species of bee-loving fungus, with a key to the
      genus for Europe.
AB  - We studied the bee specialist fungus Ascosphaera in wild solitary bees to
      investigate the diversity of the genus in nature and the ecology of these fungi
      with their bee hosts. A new morphologically distinctive species was discovered
      which also has a unique nrITS sequence. This new species, here named Ascosphaera
      callicarpa, is common on the larval feces of the solitary bee Chelostoma
      florisomne which nests in the Phragmites reeds of thatched roofs in Europe.
      Because collections of Ascosphaera from wild bees are scarce and because little
      is known about the ecology and distribution of the majority of the species in the
      genus, a key to the species thus far reported for Europe is included. 

PMID- 24086281
TI  - The LKB1 tumor suppressor as a biomarker in mouse and human tissues.
AB  - Germline mutations in the LKB1 gene (also known as STK11) cause the Peutz-Jeghers
      Syndrome, and somatic loss of LKB1 has emerged as causal event in a wide range of
      human malignancies, including melanoma, lung cancer, and cervical cancer. The
      LKB1 protein is a serine-threonine kinase that phosphorylates AMP-activated
      protein kinase (AMPK) and other downstream targets. Conditional knockout studies
      in mouse models have consistently shown that LKB1 loss promotes a highly
      metastatic phenotype in diverse tissues, and human studies have demonstrated a
      strong association between LKB1 inactivation and tumor recurrence. Furthermore,
      LKB1 deficiency confers sensitivity to distinct classes of anticancer drugs. The
      ability to reliably identify LKB1-deficient tumors is thus likely to have
      important prognostic and predictive implications. Previous research studies have
      employed polyclonal antibodies with limited success, and there is no widely
      employed immunohistochemical assay for LKB1. Here we report an assay based on a
      rabbit monoclonal antibody that can reliably detect endogenous LKB1 protein (and
      its absence) in mouse and human formalin-fixed, paraffin-embedded tissues. LKB1
      protein levels determined through this assay correlated strongly with AMPK
      phosphorylation both in mouse and human tumors, and with mRNA levels in human
      tumors. Our studies fully validate this immunohistochemical assay for LKB1 in
      paraffin-embedded formalin tissue sections. This assay should be broadly useful
      for research studies employing mouse models and also for the development of human
      tissue-based assays for LKB1 in diverse clinical settings. 

PMID- 24086282
TI  - Smell and taste in inflammatory bowel disease.
AB  - OBJECTIVE: To investigate the olfactory/gustatory functions of patients with
      inflammatory bowel disease (IBD) by smell/taste tests, and to determine if
      disease activity or medication might influence the olfactory/gustatory functions
      of patients. PATIENTS AND METHODS: In total, 59 IBD patients (37 Crohn's disease
      (CD) and 22 ulcerative colitis (UC) patients) were studied using "Sniffin'
      sticks" and "taste strips" for olfactory and gustatory tests, respectively, and
      compared to healthy controls and published normative data. RESULTS: Among IBD (CD
      and UC) patients, the values for odor threshold, but not for odor identification
      or discrimination, were significantly lower than that of the normative data.
      Further, these patients showed lower values than the normative taste values and
      the control group for all tastes, except sour; 57.6% of the IBD patients were
      hyposmic, while 30.5% were hypogeusic. Subjective self-assessments showed that
      the patients were not aware of their reduced olfactory/gustatory functions. There
      were no relevant differences in taste and smell abilities between the CD and UC
      patients. Disease activity and treatment did not influence the
      olfactory/gustatory functions. CONCLUSION: IBD (CD and UC) patients exhibited
      significant reductions in the olfactory and gustatory functions. Therefore,
      patients should be tested by smell/taste tests, in order to be adequately
      informed of their olfactory/gustatory functions and provided an understanding of
      how to overcome their limitations, and thus improve their quality of life.

PMID- 24086283
TI  - Overcoming biomass recalcitrance by combining genetically modified switchgrass
      and cellulose solvent-based lignocellulose pretreatment.
AB  - Decreasing lignin content of plant biomass by genetic engineering is believed to
      mitigate biomass recalcitrance and improve saccharification efficiency of plant
      biomass. In this study, we compared two different pretreatment methods (i.e.,
      dilute acid and cellulose solvent) on transgenic plant biomass samples having
      different lignin contents and investigated biomass saccharification efficiency.
      Without pretreatment, no correlation was observed between lignin contents of
      plant biomass and saccharification efficiency. After dilute acid pretreatment, a
      strong negative correlation between lignin content of plant samples and overall
      glucose release was observed, wherein the highest overall enzymatic glucan
      digestibility was 70% for the low-lignin sample. After cellulose solvent- and
      organic solvent-based lignocellulose fractionation pretreatment, there was no
      strong correlation between lignin contents and high saccharification efficiencies
      obtained (i.e., 80-90%). These results suggest that the importance of decreasing
      lignin content in plant biomass to saccharification was largely dependent on
      pretreatment choice and conditions. 

PMID- 24086285
TI  - A generalized model to estimate the statistical power in mitochondrial disease
      studies involving 2*k tables.
AB  - BACKGROUND: Mitochondrial DNA (mtDNA) variation (i.e. haplogroups) has been
      analyzed in regards to a number of multifactorial diseases. The statistical power
      of a case-control study determines the a priori probability to reject the null
      hypothesis of homogeneity between cases and controls. METHODS/PRINCIPAL FINDINGS:
      We critically review previous approaches to the estimation of the statistical
      power based on the restricted scenario where the number of cases equals the
      number of controls, and propose a methodology that broadens procedures to more
      general situations. We developed statistical procedures that consider different
      disease scenarios, variable sample sizes in cases and controls, and variable
      number of haplogroups and effect sizes. The results indicate that the statistical
      power of a particular study can improve substantially by increasing the number of
      controls with respect to cases. In the opposite direction, the power decreases
      substantially when testing a growing number of haplogroups. We developed mitPower
      (http://bioinformatics.cesga.es/mitpower/), a web-based interface that implements
      the new statistical procedures and allows for the computation of the a priori
      statistical power in variable scenarios of case-control study designs, or e.g.
      the number of controls needed to reach fixed effect sizes.
      CONCLUSIONS/SIGNIFICANCE: The present study provides with statistical procedures
      for the computation of statistical power in common as well as complex case
      control study designs involving 2*k tables, with special application (but not
      exclusive) to mtDNA studies. In order to reach a wide range of researchers, we
      also provide a friendly web-based tool--mitPower--that can be used in both
      retrospective and prospective case-control disease studies.

PMID- 24086284
TI  - Profiling of microRNA in human and mouse ES and iPS cells reveals overlapping but
      distinct microRNA expression patterns.
AB  - Using quantitative PCR-based miRNA arrays, we comprehensively analyzed the
      expression profiles of miRNAs in human and mouse embryonic stem (ES), induced
      pluripotent stem (iPS), and somatic cells. Immature pluripotent cells were
      purified using SSEA-1 or SSEA-4 and were used for miRNA profiling. Hierarchical
      clustering and consensus clustering by nonnegative matrix factorization showed
      two major clusters, human ES/iPS cells and other cell groups, as previously
      reported. Principal components analysis (PCA) to identify miRNAs that segregate
      in these two groups identified miR-187, 299-3p, 499-5p, 628-5p, and 888 as new
      miRNAs that specifically characterize human ES/iPS cells. Detailed direct
      comparisons of miRNA expression levels in human ES and iPS cells showed that
      several miRNAs included in the chromosome 19 miRNA cluster were more strongly
      expressed in iPS cells than in ES cells. Similar analysis was conducted with
      mouse ES/iPS cells and somatic cells, and several miRNAs that had not been
      reported to be expressed in mouse ES/iPS cells were suggested to be ES/iPS cell
      specific miRNAs by PCA. Comparison of the average expression levels of miRNAs in
      ES/iPS cells in humans and mice showed quite similar expression patterns of
      human/mouse miRNAs. However, several mouse- or human-specific miRNAs are ranked
      as high expressers. Time course tracing of miRNA levels during embryoid body
      formation revealed drastic and different patterns of changes in their levels. In
      summary, our miRNA expression profiling encompassing human and mouse ES and iPS
      cells gave various perspectives in understanding the miRNA core regulatory
      networks regulating pluripotent cells characteristics. 

PMID- 24086286
TI  - Visual acuity of simulated thalamic visual prostheses in normally sighted humans.
AB  - Simulation in normally sighted individuals is a crucial tool to evaluate the
      performance of potential visual prosthesis designs prior to human implantation of
      a device. Here, we investigated the effects of electrode count on visual acuity,
      learning rate and response time in 16 normally sighted subjects using a simulated
      thalamic visual prosthesis, providing the first performance reports for thalamic
      designs. A new letter recognition paradigm using a multiple-optotype two
      alternative forced choice task was adapted from the Snellen eye chart, and
      specifically devised to be readily communicated to both human and non-human
      primate subjects. Validation of the method against a standard Snellen acuity test
      in 21 human subjects showed no significant differences between the two tests. The
      novel task was then used to address three questions about simulations of the
      center-weighted phosphene patterns typical of thalamic designs: What are the
      expected Snellen acuities for devices with varying numbers of contacts, do
      subjects display rapid adaptation to the new visual modality, and can response
      time in the task provide clues to the mechanisms of perception in low-resolution
      artificial vision? Population performance (hit rate) was significantly above
      chance when viewing Snellen 20/200 optotypes (Log MAR 1.0) with 370 phosphenes in
      the central 10 degrees of vision, ranging to Snellen 20/800 (Log MAR 1.6) with 25
      central phosphenes. Furthermore, subjects demonstrated learning within the 1-2
      hours of task experience indicating the potential for an effective rehabilitation
      and possibly better visual performance after a longer period of training.
      Response time differences suggest that direct letter perception occurred when hit
      rate was above 75%, whereas a slower strategy like feature-based pattern matching
      was used in conditions of lower relative resolution. As pattern matching can
      substantially boost effective acuity, these results suggest post-implant therapy
      should specifically address feature detection skills. 

PMID- 24086287
TI  - Age-related hearing loss and the factors determining continued usage of hearing
      aids among elderly community-dwelling residents.
AB  - While hearing aids are recommended for people with age-related hearing loss, many
      with impaired hearing do not use them. In this study, we investigated how many
      elderly people in the study area needed hearing aids, and the factors that
      determined continued wearing of the devices. The study area was Kurabuchi Town,
      Japan, where 1,437 residents (those aged 65 years or over) were eligible for
      participation in the study; 1,414 participated, of whom, 103 (7.3%) were already
      using hearing aids at the start of the study. After the primary screening,
      hearing aids were lent to 68 participants (4.8%) who did not already have one, 38
      of whom (60.3% of the borrowers, representing 2.7% of the total aged population)
      went on to wear the hearing aid continuously. The Hearing Handicap Inventory for
      the Elderly (HHIE) score was significantly elevated among these 38 participants.
      This study indicated that hearing aids are of potential benefit to many local
      residents. Multivariate logistic regression revealed that HHIE scores were
      associated with the extent of HA usage. The adjusted odds ratio for a 1-unit
      increase in HHIE score was 1.08 (95% confidence interval: 1.02-1.14). Programs
      like this, in which people with impaired hearing are identified at the local
      level and given appropriate assistance, are useful models for future use in
      societies with aging populations. 

PMID- 24086288
TI  - Transcription profiles of endothelial cells in the rat ductus arteriosus during a
      perinatal period.
AB  - Endothelial cells (ECs) lining the blood vessels serve a variety of functions and
      play a central role in the homeostasis of the circulatory system. Since the
      ductus arteriosus (DA) has different arterial characteristics from its connecting
      vessels, we hypothesized that ECs of the DA exhibited a unique gene profile
      involved in the regulation of DA-specific morphology and function. Using a
      fluorescence-activated cell sorter, we isolated ECs from pooled tissues from the
      DA or the descending aorta of Wistar rat fetuses at full-term of gestation (F
      group) or neonates 30 minutes after birth (N group). Using anti-CD31 and anti
      CD45 antibodies as cell surface markers for ECs and hematopoietic derived cells,
      respectively, cDNAs from the CD31-positive and CD45-negative cells were
      hybridized to the Affymetrix GeneChip(r) Rat Gene 1.0 ST Array. Among 26,469 gene
      level probe sets, 82 genes in the F group and 81 genes in the N group were
      expressed at higher levels in DA ECs than in aortic ECs (p<0.05, fold
      change>2.0). In addition to well-known endothelium-enriched genes such as Tgfb2
      and Vegfa, novel DA endothelium-dominant genes including Slc38a1, Capn6, and Lrat
      were discovered. Enrichment analysis using GeneGo MetaCore software showed that
      DA endothelium-related biological processes were involved in morphogenesis and
      development. We identified many overlapping genes in each process including
      neural crest-related genes (Hoxa1, Hoxa4, and Hand2, etc) and the second heart
      field-related genes (Tbx1, Isl1, and Fgf10, etc). Moreover, we found that
      regulation of epithelial-to-mesenchymal transition, cell adhesion, and retinol
      metabolism are the active pathways involved in the network via potential
      interactions with many of the identified genes to form DA-specific endothelia. In
      conclusion, the present study uncovered several significant differences of the
      transcriptional profile between the DA and aortic ECs. Newly identified DA
      endothelium-dominant genes may play an important role in DA-specific functional
      and morphologic characteristics. 

PMID- 24086289
TI  - A comparison of two spelling Brain-Computer Interfaces based on visual P3 and
      SSVEP in Locked-In Syndrome.
AB  - OBJECTIVES: We study the applicability of a visual P3-based and a Steady State
      Visually Evoked Potentials (SSVEP)-based Brain-Computer Interfaces (BCIs) for
      mental text spelling on a cohort of patients with incomplete Locked-In Syndrome
      (LIS). METHODS: Seven patients performed repeated sessions with each BCI. We
      assessed BCI performance, mental workload and overall satisfaction for both
      systems. We also investigated the effect of the quality of life and level of
      motor impairment on the performance. RESULTS: All seven patients were able to
      achieve an accuracy of 70% or more with the SSVEP-based BCI, compared to 3
      patients with the P3-based BCI, showing a better performance with the SSVEP BCI
      than with the P3 BCI in the studied cohort. Moreover, the better performance of
      the SSVEP-based BCI was accompanied by a lower mental workload and a higher
      overall satisfaction. No relationship was found between BCI performance and level
      of motor impairment or quality of life. CONCLUSION: Our results show a better
      usability of the SSVEP-based BCI than the P3-based one for the sessions performed
      by the tested population of locked-in patients with respect to all the criteria
      considered. The study shows the advantage of developing alternative BCIs with
      respect to the traditional matrix-based P3 speller using different designs and
      signal modalities such as SSVEPs to build a faster, more accurate, less mentally
      demanding and more satisfying BCI by testing both types of BCIs on a convenience
      sample of LIS patients.

PMID- 24086290
TI  - The influence of transcription factor competition on the relationship between
      occupancy and affinity.
AB  - Transcription factors (TFs) are proteins that bind to specific sites on the DNA
      and regulate gene activity. Identifying where TF molecules bind and how much time
      they spend on their target sites is key to understanding transcriptional
      regulation. It is usually assumed that the free energy of binding of a TF to the
      DNA (the affinity of the site) is highly correlated to the amount of time the TF
      remains bound (the occupancy of the site). However, knowing the binding energy is
      not sufficient to infer actual binding site occupancy. This mismatch between the
      occupancy predicted by the affinity and the observed occupancy may be caused by
      various factors, such as TF abundance, competition between TFs or the arrangement
      of the sites on the DNA. We investigated the relationship between the affinity of
      a TF for a set of binding sites and their occupancy. In particular, we considered
      the case of the transcription factor lac repressor (lacI) in E.coli, and
      performed stochastic simulations of the TF dynamics on the DNA for various
      combinations of lacI abundance and competing TFs that contribute to
      macromolecular crowding. We also investigated the relationship of site occupancy
      and the information content of position weight matrices (PWMs) used to represent
      binding sites. Our results showed that for medium and high affinity sites, TF
      competition does not play a significant role for genomic occupancy except in
      cases when the abundance of the TF is significantly increased, or when the PWM
      displays relatively low information content. Nevertheless, for medium and low
      affinity sites, an increase in TF abundance (for both cognate and non-cognate
      molecules) leads to an increase in occupancy at several sites. 

PMID- 24086291
TI  - Effective connectivity reveals strategy differences in an expert calculator.
AB  - Mathematical reasoning is a core component of cognition and the study of experts
      defines the upper limits of human cognitive abilities, which is why we are
      fascinated by peak performers, such as chess masters and mental calculators.
      Here, we investigated the neural bases of calendrical skills, i.e. the ability to
      rapidly identify the weekday of a particular date, in a gifted mental calculator
      who does not fall in the autistic spectrum, using functional MRI. Graph-based
      mapping of effective connectivity, but not univariate analysis, revealed distinct
      anatomical location of "cortical hubs" supporting the processing of well
      practiced close dates and less-practiced remote dates: the former engaged
      predominantly occipital and medial temporal areas, whereas the latter were
      associated mainly with prefrontal, orbitofrontal and anterior cingulate
      connectivity. These results point to the effect of extensive practice on the
      development of expertise and long term working memory, and demonstrate the role
      of frontal networks in supporting performance on less practiced calculations,
      which incur additional processing demands. Through the example of calendrical
      skills, our results demonstrate that the ability to perform complex calculations
      is initially supported by extensive attentional and strategic resources, which,
      as expertise develops, are gradually replaced by access to long term working
      memory for familiar material. 

PMID- 24086292
TI  - Are sitting occupations associated with increased all-cause, cancer, and
      cardiovascular disease mortality risk? A pooled analysis of seven British
      population cohorts.
AB  - BACKGROUND: There is mounting evidence for associations between sedentary
      behaviours and adverse health outcomes, although the data on occupational sitting
      and mortality risk remain equivocal. The aim of this study was to determine the
      association between occupational sitting and cardiovascular, cancer and all-cause
      mortality in a pooled sample of seven British general population cohorts.
      METHODS: The sample comprised 5380 women and 5788 men in employment who were
      drawn from five Health Survey for England and two Scottish Health Survey cohorts.
      Participants were classified as reporting standing, walking or sitting in their
      work time and followed up over 12.9 years for mortality. Data were modelled using
      Cox proportional hazard regression adjusted for age, waist circumference, self
      reported general health, frequency of alcohol intake, cigarette smoking, non
      occupational physical activity, prevalent cardiovascular disease and cancer at
      baseline, psychological health, social class, and education. RESULTS: In total
      there were 754 all-cause deaths. In women, a standing/walking occupation was
      associated with lower risk of all-cause (fully adjusted hazard ratio [HR] = 0.68,
      95% CI 0.52-0.89) and cancer (HR = 0.60, 95% CI 0.43-0.85) mortality, compared to
      sitting occupations. There were no associations in men. In analyses with combined
      occupational type and leisure-time physical activity, the risk of all-cause
      mortality was lowest in participants with non-sitting occupations and high
      leisure-time activity. CONCLUSIONS: Sitting occupations are linked to increased
      risk for all-cause and cancer mortality in women only, but no such associations
      exist for cardiovascular mortality in men or women.

PMID- 24086293
TI  - The effect of pro-inflammatory conditioning and/or high glucose on telomere
      shortening of aging fibroblasts.
AB  - Cardiovascular disease and diabetes have been linked to shorter telomeres, but it
      is not yet clear which risk factors contribute to shorter telomeres in patients.
      Our aim was to examine whether pro-inflammatory conditioning, in combination or
      not with high glucose, result in a higher rate of telomere shortening during in
      vitro cellular ageing. Human fibroblasts from four donors were cultured for 90
      days in: 1) medium lacking ascorbic acid only, 2) 10 mM buthionine sulphoximine
      (BSO) (pro-oxidant), 3) 25 mM D-glucose, 4) 1 ng/ml IL1B and 5) 25 mM D-glucose+1
      ng/ml IL1B. Telomere length was measured with qPCR and intracellular reactive
      oxygen species (ROS) content and cell death with flow cytometry. Cultures treated
      with high glucose and BSO displayed a significantly lower growth rate, and
      cultures treated with IL1B showed a trend towards a higher growth rate, compared
      to the control [Glucose:0.14 PD/day, p<0.001, BSO: 0.11 PD/day, p = 0.006 and
      IL1B: 0.19 PD/day, p = 0.093 vs. CONTROL: 0.16 PD/day]. Telomere shortening with
      time was significantly accelerated in cultures treated with IL1B compared to the
      control [IL1B:-0.8%/day (95%CI:-1.1, -0.5) vs. CONTROL: -0.6%/day (95%CI:-0.8, 
      0.3), p = 0.012]. The hastening of telomere shortening by IL1B was only in part
      attenuated after adjustment for the number of cell divisions [IL1B:-4.1%/PD
      (95%CI:-5.7, -2.4) vs. CONTROL: -2.5%/PD (95%CI:-4.4, -0.7), p = 0.067]. The
      intracellular ROS content displayed 69% increase (p = 0.033) in BSO compared to
      the control. In aging fibroblasts, pro-inflammatory conditioning aggravates the
      shortening of telomeres, an effect which was only in part driven by increased
      cell turnover. High glucose alone did not result in greater production of ROS or
      telomere shortening.

PMID- 24086294
TI  - Do fish perceive anaesthetics as aversive?
AB  - This study addresses a fundamental question in fish welfare: are the anaesthetics
      used for fish aversive? Despite years of routine general use of many agents,
      within both scientific research and aquaculture, there is a paucity of
      information regarding their tolerance and associated behavioural responses by
      fish. This study examined nine of the most commonly used fish anaesthetic agents,
      and performed preference tests using adult mixed sex zebrafish (Danio rerio), the
      most commonly held laboratory fish. Video tracking software quantified swimming
      behaviour related to aversion for each anaesthetic at 50% of its standard
      recommended dose compared with clean water in a flow-through chemotaxic choice
      chamber. Results suggest that several commonly used anaesthetics were aversive,
      including two of the most commonly recommended and used: MS222 (ethyl 3
      aminobenzoate methanesulphate) and benzocaine. For ethical best practice, it is
      recommended that compounds that are aversive, even at low concentration, should
      no longer be used routinely for anaesthesia or indeed the first step of humane
      euthanasia of adult zebrafish. Two agents were found not to induce aversive
      behavioural responses: etomidate and 2,2,2 tribromoethanol. For the millions of
      adult zebrafish used in laboratories and breeding worldwide, etomidate appears
      best suited for future routine humane use.

PMID- 24086295
TI  - The RosettaCon 2012 Special Collection: Code Writ on Water, Documentation Writ in
      Stone.

PMID- 24086296
TI  - Personality, gender, and age in the language of social media: the open-vocabulary
      approach.
AB  - We analyzed 700 million words, phrases, and topic instances collected from the
      Facebook messages of 75,000 volunteers, who also took standard personality tests,
      and found striking variations in language with personality, gender, and age. In
      our open-vocabulary technique, the data itself drives a comprehensive exploration
      of language that distinguishes people, finding connections that are not captured
      with traditional closed-vocabulary word-category analyses. Our analyses shed new
      light on psychosocial processes yielding results that are face valid (e.g.,
      subjects living in high elevations talk about the mountains), tie in with other
      research (e.g., neurotic people disproportionately use the phrase 'sick of' and
      the word 'depressed'), suggest new hypotheses (e.g., an active life implies
      emotional stability), and give detailed insights (males use the possessive 'my'
      when mentioning their 'wife' or 'girlfriend' more often than females use 'my'
      with 'husband' or 'boyfriend'). To date, this represents the largest study, by an
      order of magnitude, of language and personality. 

PMID- 24086297
TI  - Sticking under wet conditions: the remarkable attachment abilities of the torrent
      frog, Staurois guttatus.
AB  - Tree frogs climb smooth surfaces utilising capillary forces arising from an air
      fluid interface around their toe pads, whereas torrent frogs are able to climb in
      wet environments near waterfalls where the integrity of the meniscus is at risk.
      This study compares the adhesive capabilities of a torrent frog to a tree frog,
      investigating possible adaptations for adhesion under wet conditions. We
      challenged both frog species to cling to a platform which could be tilted from
      the horizontal to an upside-down orientation, testing the frogs on different
      levels of roughness and water flow. On dry, smooth surfaces, both frog species
      stayed attached to overhanging slopes equally well. In contrast, under both low
      and high flow rate conditions, the torrent frogs performed significantly better,
      even adhering under conditions where their toe pads were submerged in water,
      abolishing the meniscus that underlies capillarity. Using a transparent platform
      where areas of contact are illuminated, we measured the contact area of frogs
      during platform rotation under dry conditions. Both frog species not only used
      the contact area of their pads to adhere, but also large parts of their belly and
      thigh skin. In the tree frogs, the belly and thighs often detached on steeper
      slopes, whereas the torrent frogs increased the use of these areas as the slope
      angle increased. Probing small areas of the different skin parts with a force
      transducer revealed that forces declined significantly in wet conditions, with
      only minor differences between the frog species. The superior abilities of the
      torrent frogs were thus due to the large contact area they used on steep,
      overhanging surfaces. SEM images revealed slightly elongated cells in the
      periphery of the toe pads in the torrent frogs, with straightened channels in
      between them which could facilitate drainage of excess fluid underneath the pad. 

PMID- 24086298
TI  - Non-adaptive phenotypic evolution of the endangered carnivore Lycaon pictus.
AB  - Decline in wild populations as a result of anthropogenic impact is widely
      considered to have evolutionary consequences for the species concerned. Here we
      examine changes in developmental stability in the painted hunting dog (Lycaon
      pictus), which once occupied most of sub-Saharan Africa but has undergone a
      dramatic population decline in the last century. Fluctuating asymmetry (FA) was
      used as an indicator of developmental stability and measured in museum skull
      specimens spanning a hundred year period. A comparison with the more ubiquitous
      black-backed jackal (Canis mesomelas) revealed FA in L. pictus to be high.
      Furthermore, the data indicate a temporal increase in FA over time in L. pictus,
      corresponding to the period of its population decline. The high rate of change is
      compatible with genetic drift although environmental factors are also likely to
      be important. Lowering developmental stability over time may have direct fitness
      consequences and as such represents an unacknowledged threat to future resilience
      of the population. 

PMID- 24086299
TI  - Solvent dependency of the UV-Vis spectrum of indenoisoquinolines: role of keto
      oxygens as polarity interaction probes.
AB  - Indenoisoquinolines are the most promising non-campthotecins topoisomerase IB
      inhibitors. We present an integrated experimental/computational investigation of
      the UV-Vis spectra of the IQNs parental compound (NSC314622) and two of its
      derivatives (NSC724998 and NSC725776) currently undergoing Phase I clinical
      trials. In all the three compounds a similar dependence of the relative
      absorption intensities at 270 nm and 290 nm on solvent polarity is found. The
      keto-oxygens in positions 5 and 11 of the molecular scaffold of the molecule are
      the principal chromophores involved in this dependence. Protic interactions on
      these sites are also found to give rise to absorptions at wavelength <250 nm
      observed in water solution, due to the stabilization of highly polarized
      tautomers of the molecule. These results suggest that the keto-oxygens are
      important polarizable groups that can act as useful interactors with the
      molecular receptor, providing at the same time an useful fingerprint for the
      monitoring of the drug binding to topoisomerase IB. 

PMID- 24086301
TI  - Digital radiology to improve the quality of care in countries with limited
      resources: a feasibility study from Angola.
AB  - OBJECTIVE: Sub-standard quality in X-ray image acquisition and interpretation is
      common in low-resource countries, and can ultimately result in higher patient
      morbidity and mortality. This study aimed at evaluating; 1) feasibility of
      implementing a digital X-ray device in a second level hospital in Angola; 2)
      quality of digital X-ray images, when digital radiology was in the hands of local
      technicians; 3) feasibility of digital teleradiology and its potential impact on
      case management. METHODS: We developed and tested at the Hospital Divina
      Providencia (HDP) in Luanda, Angola, a digital X-ray device and a telemedicine
      network to acquire and print digital X-ray images and send them as DICOM files
      for remote consultation. RESULTS: 20,564 digital X-ray images were made at HDP
      from November 2010 to December 2012, with no major technical problems and no need
      for on-site supervision. Digital radiology largely improved the number of X-ray
      images of good and very good quality (100% of images with digital radiology,
      compared to 15% of screen-film images, p<0.0001). Teleradiology using digital
      images was used in 7.6% of paediatric cases, and provided, in these cases, an
      important contribution to case management. CONCLUSIONS: The implementation of a
      digital X-ray device is feasible in low resource settings with significant
      improvement in quality of X-ray images compared to standard screen film
      radiology.

PMID- 24086300
TI  - Microtubule Actin Cross-linking Factor 1 regulates cardiomyocyte microtubule
      distribution and adaptation to hemodynamic overload.
AB  - Aberrant cardiomyocyte microtubule growth is a feature of pressure overload
      induced cardiac hypertrophy believed to contribute to left ventricular (LV)
      dysfunction. Microtubule Actin Cross-linking Factor 1 (MACF1/Acf7) is a 600 kd
      spectraplakin that stabilizes and guides microtubule growth along actin
      filaments. MACF1 is expressed in the heart, but its impact on cardiac
      microtubules, and how this influences cardiac structure, function, and adaptation
      to hemodynamic overload is unknown. Here we used inducible cardiac-specific MACF1
      knockout mice (MACF1 KO) to determine the impact of MACF1 on cardiac microtubules
      and adaptation to pressure overload (transverse aortic constriction (TAC).In
      adult mouse hearts, MACF1 expression was low under basal conditions, but
      increased significantly in response to TAC. While MACF1 KO had no observable
      effect on heart size or function under basal conditions, MACF1 KO exacerbated TAC
      induced LV hypertrophy, LV dilation and contractile dysfunction. Interestingly,
      subcellular fractionation of ventricular lysates revealed that MACF1 KO altered
      microtubule distribution in response to TAC, so that more tubulin was associated
      with the cell membrane fraction. Moreover, TAC induced microtubule redistribution
      into this cell membrane fraction in both WT and MACF1 KO mice correlated
      strikingly with the level of contractile dysfunction (r(2) = 0.786, p<.001).
      MACF1 disruption also resulted in reduction of membrane caveolin 3 levels, and
      increased levels of membrane PKCalpha and beta1 integrin after TAC, suggesting
      MACF1 function is important for spatial regulation of several physiologically
      relevant signaling proteins during hypertrophy. Together, these data identify for
      the first time, a role for MACF1 in cardiomyocyte microtubule distribution and in
      adaptation to hemodynamic overload. 

PMID- 24086302
TI  - Transcriptome and expression profile analysis of highly resistant and susceptible
      banana roots challenged with Fusarium oxysporum f. sp. cubense tropical race 4.
AB  - Banana wilt disease, caused by the fungal pathogen Fusarium oxysporum f. sp.
      cubense 4 (Foc4), is regarded as one of the most devastating diseases worldwide.
      Cavendish cultivar 'Yueyoukang 1' was shown to have significantly lower disease
      severity and incidence compared with susceptible cultivar 'Brazilian' in
      greenhouse and field trials. De novo sequencing technology was previously
      performed to investigate defense mechanism in middle resistant 'Nongke No 1'
      banana, but not in highly resistant cultivar 'Yueyoukang 1'. To gain more
      insights into the resistance mechanism in banana against Foc4, Illumina Solexa
      sequencing technology was utilized to perform transcriptome sequencing of
      'Yueyoukang 1' and 'Brazilian' and characterize gene expression profile changes
      in the both two cultivars at days 0.5, 1, 3, 5 and 10 after infection with Foc4.
      The results showed that more massive transcriptional reprogramming occurs due to
      Foc4 treatment in 'Yueyoukang 1' than 'Brazilian', especially at the first three
      time points, which suggested that 'Yueyoukang 1' had much faster defense response
      against Foc4 infection than 'Brazilian'. Expression patterns of genes involved in
      'Plant-pathogen interaction' and 'Plant hormone signal transduction' pathways
      were analyzed and compared between the two cultivars. Defense genes associated
      with CEBiP, BAK1, NB-LRR proteins, PR proteins, transcription factor and cell
      wall lignification were expressed stronger in 'Yueyoukang 1' than 'Brazilian',
      indicating that these genes play important roles in banana against Foc4
      infection. However, genes related to hypersensitive reaction (HR) and senescence
      were up-regulated in 'Brazilian' but down-regulated in 'Yueyoukang 1', which
      suggested that HR and senescence may contribute to Foc4 infection. In addition,
      the resistance mechanism in highly resistant 'Yueyoukang 1' was found to differ
      from that in middle resistant 'Nongke No 1' banana. These results explain the
      resistance in the highly resistant cultivar and provide more insights in
      understanding the compatible and incompatible interactions between banana and
      Foc4. 

PMID- 24086303
TI  - The human minor histocompatibility antigen 1 is a RhoGAP.
AB  - The human minor Histocompatibility Antigen HMHA-1 is a major target of immune
      responses after allogeneic stem cell transplantation applied for the treatment of
      leukemia and solid tumors. The restriction of its expression to hematopoietic
      cells and many solid tumors raised questions regarding its cellular functions.
      Sequence analysis of the HMHA-1 encoding HMHA1 protein revealed the presence of a
      possible C-terminal RhoGTPase Activating Protein (GAP) domain and an N-terminal
      BAR domain. Rho-family GTPases, including Rac1, Cdc42, and RhoA are key
      regulators of the actin cytoskeleton and control cell spreading and migration.
      RhoGTPase activity is under tight control as aberrant signaling can lead to
      pathology, including inflammation and cancer. Whereas Guanine nucleotide Exchange
      Factors (GEFs) mediate the exchange of GDP for GTP resulting in RhoGTPase
      activation, GAPs catalyze the low intrinsic GTPase activity of active RhoGTPases,
      resulting in inactivation. Here we identify the HMHA1 protein as a novel RhoGAP.
      We show that HMHA1 constructs, lacking the N-terminal region, negatively regulate
      the actin cytoskeleton as well as cell spreading. Furthermore, we show that HMHA1
      regulates RhoGTPase activity in vitro and in vivo. Finally, we demonstrate that
      the HMHA1 N-terminal BAR domain is auto-inhibitory as HMHA1 mutants lacking this
      region, but not full-length HMHA1, showed GAP activity towards RhoGTPases. In
      conclusion, this study shows that HMHA1 acts as a RhoGAP to regulate GTPase
      activity, cytoskeletal remodeling and cell spreading, which are crucial functions
      in normal hematopoietic and cancer cells. 

PMID- 24086304
TI  - Dairy products consumption and risk of type 2 diabetes: systematic review and
      dose-response meta-analysis.
AB  - BACKGROUND: The consumption of dairy products may influence the risk of type 2
      diabetes mellitus (T2DM), but inconsistent findings have been reported. Moreover,
      large variation in the types of dairy intake has not yet been fully explored.
      METHODS AND RESULTS: We conducted a systematic review and meta-analysis to
      clarify the dose-response association of dairy products intake and T2DM risk. We
      searched PubMed, EMBASE and Scopus for studies of dairy products intake and T2DM
      risk published up to the end of October 2012. Random-effects models were used to
      estimate summary relative risk (RR) statistics. Dose-response relations were
      evaluated using data from different dairy products in each study. We included 14
      articles of cohort studies that reported RR estimates and 95% confidence
      intervals (95% CIs) of T2DM with dairy products intake. We found an inverse
      linear association of consumption of total dairy products (13 studies), low-fat
      dairy products (8 studies), cheese (7 studies) and yogurt (7 studies) and risk of
      T2DM. The pooled RRs were 0.94 (95% CI 0.91-0.97) and 0.88 (0.84-0.93) for 200
      g/day total and low-fat dairy consumption, respectively. The pooled RRs were 0.80
      (0.69-0.93) and 0.91 (0.82-1.00) for 30 g/d cheese and 50 g/d yogurt consumption,
      respectively. We also found a nonlinear association of total and low-fat dairy
      intake and T2DM risk, and the inverse association appeared to be strongest within
      200 g/d intake. CONCLUSION: A modest increase in daily intake of dairy products
      such as low fat dairy, cheese and yogurt may contribute to the prevention of
      T2DM, which needs confirmation in randomized controlled trials.

PMID- 24086305
TI  - Delayed wound repair in sepsis is associated with reduced local pro-inflammatory
      cytokine expression.
AB  - Sepsis is one of the main causes for morbidity and mortality in hospitalized
      patients. Moreover, sepsis associated complications involving impaired wound
      healing are common. Septic patients often require surgical interventions that in
      turn may lead to further complications caused by impaired wound healing. We
      established a mouse model to the study delayed wound healing during sepsis
      distant to the septic focus point. For this reason cecal ligation and puncture
      (CLP) was combined with the creation of a superficial wound on the mouse ear.
      Control animals received the same procedure without CPL. Epithelialization was
      measured every second day by direct microscopic visualization up to complete
      closure of the wound. As interplay of TNF-alpha, TGF-beta, matrix
      metalloproteinases (MMP), and tissue inhibitors of metalloproteinases (TIMP) is
      important in wound healing in general, TNF-alpha, TGF-beta, MMP7, and TIMP1 were
      assessed immunohistochemical in samples of wounded ears harvested on days 2, 6,
      10 and 16 after wounding. After induction of sepsis, animals showed a significant
      delay in wound epithelialization from day 2 to 12 compared to control animals.
      Complete wound healing was attained after mean 12.2+/- standard deviation (SD)
      3.0 days in septic animals compared to 8.7+/- SD 1.7 days in the control group.
      Septic animals showed a significant reduction in local pro-inflammatory cytokine
      level of TNF-alpha on day 2 and day 6 as well as a reduced expression of TGF-beta
      on day 2 in wounds. A significant lower expression of MMP7 as well as TIMP1 was
      also observed on day 2 after wounding. The induction of sepsis impairs wound
      healing distant to the septic focus point. We could demonstrate that expression
      of important cytokines for wound repair is deregulated after induction of sepsis.
      Thus restoring normal cytokine response locally in wounds could be a good
      strategy to enhance wound repair in sepsis. 

PMID- 24086306
TI  - A developmental stage-specific switch from DAZL to BOLL occurs during fetal
      oogenesis in humans, but not mice.
AB  - The Deleted in Azoospermia gene family encodes three germ cell-specific RNA
      binding proteins (DAZ, DAZL and BOLL) that are essential for gametogenesis in
      diverse species. Targeted disruption of Boll in mice causes male-specific
      spermiogenic defects, but females are apparently fertile. Overexpression of human
      BOLL promotes the derivation of germ cell-like cells from genetically female
      (XX), but not male (XY) human ES cells however, suggesting a functional role for
      BOLL in regulating female gametogenesis in humans. Whether BOLL is expressed
      during oogenesis in mammals also remains unclear. We have therefore investigated
      the expression of BOLL during fetal oogenesis in humans and mice. We demonstrate
      that BOLL protein is expressed in the germ cells of the human fetal ovary, at a
      later developmental stage than, and almost mutually-exclusive to, the expression
      of DAZL. Strikingly, BOLL is downregulated, and DAZL re-expressed, as primordial
      follicles form, revealing BOLL expression to be restricted to a narrow window
      during fetal oogenesis. By quantifying the extent of co-expression of DAZL and
      BOLL with markers of meiosis, we show that this window likely corresponds to the
      later stages of meiotic prophase I. Finally, we demonstrate that Boll is also
      transiently expressed during oogenesis in the fetal mouse ovary, but is
      simultaneously co-expressed within the same germ cells as Dazl. These data reveal
      significant similarities and differences between the expression of BOLL
      homologues during oogenesis in humans and mice, and raise questions as to the
      validity of the Boll(-/-) mouse as a model for understanding BOLL function during
      human oogenesis. 

PMID- 24086307
TI  - Secretoneurin gene therapy improves blood flow in an ischemia model in type 1
      diabetic mice by enhancing therapeutic neovascularization.
AB  - Deficient angiogenesis after ischemia may contribute to worse outcome of
      peripheral arterial disease in patients with diabetes mellitus. Based on our
      previous work where we demonstrated that Secretoneurin (SN) is up-regulated under
      hypoxic conditions and enhances angiogenesis, we analyzed the therapeutic
      potential of SN gene therapy using a model of severe hind limb ischemia in
      streptozotocin-induced diabetic mice (STZ-DM). After induction of hind limb
      ischemia, blood flow was assessed by means of laser Doppler perfusion imaging
      (LDPI) and increased blood perfusion in the SN-treated animal group was observed.
      These results were complemented by the clinical observation of reduced necrosis
      and by an increased number of capillaries and arterioles in the SN-treated animal
      group. In vitro, we found that SN is capable of promoting proliferation and
      chemotaxis and reduces apoptosis in HUVECs cultured under hyperglycemic
      conditions. Additionally, SN activated ERK, eNOS and especially AKT as well as
      EGF-receptor in hyperglycemic HUVECs. In conclusion, we show that SN gene therapy
      improves post-ischemic neovascularization in diabetic mice through stimulation of
      angiogenesis and arteriogenesis indicating a possible therapeutic role of this
      factor in ischemia-related diseases in diabetic patients. 

PMID- 24086308
TI  - Unique structure and dynamics of the EphA5 ligand binding domain mediate its
      binding specificity as revealed by X-ray crystallography, NMR and MD simulations.
AB  - The 16 EphA and EphB receptors represent the largest family of receptor tyrosine
      kinases, and their interactions with 9 ephrin-A and ephrin-B ligands initiate
      bidirectional signals controlling many physiological and pathological processes.
      Most interactions occur between receptor and ephrins of the same class, and only
      EphA4 can bind all A and B ephrins. To understand the structural and dynamic
      principles that enable Eph receptors to utilize the same jellyroll beta-sandwich
      fold to bind ephrins, the VAPB-MSP domain, peptides and small molecules, we have
      used crystallography, NMR and molecular dynamics (MD) simulations to determine
      the first structure and dynamics of the EphA5 ligand-binding domain (LBD), which
      only binds ephrin-A ligands. Unexpectedly, despite being unbound, the high
      affinity ephrin-binding pocket of EphA5 resembles that of other Eph receptors
      bound to ephrins, with a helical conformation over the J-K loop and an open
      pocket. The openness of the pocket is further supported by NMR hydrogen/deuterium
      exchange data and MD simulations. Additionally, the EphA5 LBD undergoes
      significant picosecond-nanosecond conformational exchanges over the loops, as
      revealed by NMR and MD simulations, but lacks global conformational exchanges on
      the microsecond-millisecond time scale. This is markedly different from the EphA4
      LBD, which shares 74% sequence identity and 87% homology. Consequently, the
      unbound EphA5 LBD appears to comprise an ensemble of open conformations that have
      only small variations over the loops and appear ready to bind ephrin-A ligands.
      These findings show how two proteins with high sequence homology and structural
      similarity are still able to achieve distinctive binding specificities through
      different dynamics, which may represent a general mechanism whereby the same
      protein fold can serve for different functions. Our findings also suggest that a
      promising strategy to design agonists/antagonists with high affinity and
      selectivity might be to target specific dynamic states of the Eph receptor LBDs. 

PMID- 24086309
TI  - Differential effects of Parkinson's disease and dopamine replacement on memory
      encoding and retrieval.
AB  - Increasingly memory deficits are recognized in Parkinson's disease (PD). In PD,
      the dopamine-producing cells of the substantia nigra (SN) are significantly
      degenerated whereas those in the ventral tegmental area (VTA) are relatively
      spared. Dopamine-replacement medication improves cognitive processes that
      implicate the SN-innervated dorsal striatum but is thought to impair those that
      depend upon the VTA-supplied ventral striatum, limbic and prefrontal cortices.
      Our aim was to examine memory encoding and retrieval in PD and how they are
      affected by dopamine replacement. Twenty-nine PD patients performed the Rey
      Auditory Verbal Learning Test (RAVLT) and a non-verbal analogue, the Aggie
      Figures Learning Test (AFLT), both on and off dopaminergic medications. Twenty
      seven, age-matched controls also performed these memory tests twice and their
      data were analyzed to correspond to the ON-OFF order of the PD patients to whom
      they were matched. We contrasted measures that emphasized with those that
      accentuated retrieval and investigated the effect of PD and dopamine-replacement
      on these processes separately. For PD patients relative to controls, encoding
      performance was normal in the off state and was impaired on dopaminergic
      medication. Retrieval was impaired off medication and improved by dopamine
      repletion. This pattern of findings suggests that VTA-innervated brain regions
      such as ventral striatum, limbic and prefrontal cortices are implicated in
      encoding, whereas the SN-supplied dorsal striatum mediates retrieval.
      Understanding this pattern of spared functions and deficits in PD, and the effect
      of dopamine replacement on these distinct memory processes, should prompt closer
      scrutiny of patients' cognitive complaints to inform titration of dopamine
      replacement dosages along with motor symptoms. 

PMID- 24086310
TI  - DNA repair gene XRCC1 polymorphisms and head and neck cancer risk: an updated
      meta-analysis including 16344 subjects.
AB  - BACKGROUND: DNA repair gene X-ray repair cross complementing group 1 (XRCC1)
      plays an important role in the maintenance of the genomic integrity and
      protection of cells from DNA damage. Sequence variation in XRCC1 gene may alter
      head and neck cancer (HNC) susceptibility. However, these results are
      inconclusive. To derive a more precise estimation of the relationship between
      XRCC1 polymorphism and HNC risk, we undertook a meta-analysis involving 16,344
      subjects. METHODS: A search of the literature by PubMed, Embase, Web of Science
      and China National Knowledge Infrastructure was performed to identify studies
      based on the predetermined inclusion criteria. The odds ratio (OR) with 95%
      confidence interval (CI) was combined using a random-effects model or a fixed
      effects model. RESULTS: Twenty-nine studies consisting of 6,719 cases and 9,627
      controls were identified and analyzed. Overall, no evidence of significant
      association was observed between XRCC1 Arg194Trp, XRCC1 Arg280His, XRCC1
      Arg399Gln genotypes and the risk of HNC in any genetic models. Subgroup analyses
      according to ethnicity, tumor site, publication year, genotyping method also
      detected no significant association in any subgroup, except that oral cancer was
      associated with Arg194Trp variant in recessive model. Furthermore, no significant
      effect of these polymorphisms interacted with smoking on HNC risk was detected
      but Arg194Trp homozygous variant. CONCLUSION: In conclusion, this meta-analysis
      suggests that the XRCC1 Arg194Trp, Arg280His and Arg399Gln polymorphism may not
      involve in HNC susceptibility. Further studies about gene-gene and gene
      environment interactions in different populations are required.

PMID- 24086311
TI  - CoCiter: an efficient tool to infer gene function by assessing the significance
      of literature co-citation.
AB  - A routine approach to inferring functions for a gene set is by using function
      enrichment analysis based on GO, KEGG or other curated terms and pathways.
      However, such analysis requires the existence of overlapping genes between the
      query gene set and those annotated by GO/KEGG. Furthermore, GO/KEGG databases
      only maintain a very restricted vocabulary. Here, we have developed a tool called
      "CoCiter" based on literature co-citations to address the limitations in
      conventional function enrichment analysis. Co-citation analysis is widely used in
      ranking articles and predicting protein-protein interactions (PPIs). Our
      algorithm can further assess the co-citation significance of a gene set with any
      other user-defined gene sets, or with free terms. We show that compared with the
      traditional approaches, CoCiter is a more accurate and flexible function
      enrichment analysis method. CoCiter is freely available at
      www.picb.ac.cn/hanlab/cociter/. 

PMID- 24086312
TI  - CpG usage in RNA viruses: data and hypotheses.
AB  - CpG repression in RNA viruses has been known for decades, but a reasonable
      explanation has not yet been proposed to explain this phenomenon. In this study,
      we calculated the CpG odds ratio of all RNA viruses that have available genome
      sequences and analyzed the correlation with their genome polarity, base
      composition, synonymous codon usage, phylogenetic relationship, and host. The
      results indicated that the viral base composition, synonymous codon usage and
      host selection were the dominant factors that determined the CpG bias in RNA
      viruses. CpG usage variation between the different viral groups was caused by
      different combinations of these pressures, which also differed from each other in
      strength. The consistent under-representation of CpG usage in -ssRNA viruses is
      determined predominantly by base composition, which may be a consequence of the
      U/A preferred mutation bias of -ssRNA viruses, whereas the CpG usage of +ssRNA
      viruses is affected greatly by their hosts. As a result, most +ssRNA viruses
      mimic their hosts' CpG usage. Unbiased CpG usage in dsRNA viruses is most likely
      a result of their dsRNA genome, which allows the viruses to escape from the host
      driven CpG elimination pressure. CpG was under-represented in all reverse
      transcribing viruses (RT viruses), suggesting that DNA methylation is an
      important factor affecting the CpG usage of retroviruses. However, vertebrate
      infecting RT viruses may also suffer host' CpG elimination pressure that also
      acts on +ssRNA viruses, which results in further under-representation of CpG in
      the vertebrate-infecting RT viruses. 

PMID- 24086313
TI  - Toll-like receptor 2 or toll-like receptor 4 deficiency does not modify lupus in
      MRLlpr mice.
AB  - Systemic lupus erythematosus is an autoimmune disease with a high morbidity and
      nephritis is a common manifestation. Previous studies in murine lupus models have
      suggest a role for Toll-like receptor 2 and 4. We examined the role of these
      molecules in MRL lpr mice which is one of the most established and robust murine
      models. We compared disease parameters in Toll-like receptor 2 or Toll-like
      receptor 4 deficient mice with their littermate controls. We found no difference
      in the severity of glomerulonephritis as assessed by histology, serum creatinine
      and albuminuria when Toll-like receptor 2 or Toll-like receptor 4 deficient
      MRLlpr mice were compared with Toll-like receptor sufficient controls. We also
      found similar levels of anti-dsDNA and anti-ssDNA antibodies. These results show
      that Toll-like receptor 2 and Toll-like receptor 4 do not play a significant role
      in MRLlpr mice, and therefore they may not be important in human lupus. 

PMID- 24086314
TI  - Efficient computation of k-Nearest Neighbour Graphs for large high-dimensional
      data sets on GPU clusters.
AB  - This paper presents an implementation of the brute-force exact k-Nearest Neighbor
      Graph (k-NNG) construction for ultra-large high-dimensional data cloud. The
      proposed method uses Graphics Processing Units (GPUs) and is scalable with multi
      levels of parallelism (between nodes of a cluster, between different GPUs on a
      single node, and within a GPU). The method is applicable to homogeneous computing
      clusters with a varying number of nodes and GPUs per node. We achieve a 6-fold
      speedup in data processing as compared with an optimized method running on a
      cluster of CPUs and bring a hitherto impossible [Formula: see text]-NNG
      generation for a dataset of twenty million images with 15 k dimensionality into
      the realm of practical possibility. 

PMID- 24086315
TI  - Larger fig wasps are more careful about which figs to enter--with good reason.
AB  - Floral longevity reflects a balance between gains in pollinator visitation and
      the costs of flower maintenance. Because rewards to pollinators change over time,
      older flowers may be less attractive, reducing the value of extended longevity.
      Un-pollinated figs, the inflorescences of Ficus species, can remain receptive for
      long periods, but figs that are older when entered by their host-specific fig
      wasp pollinators produce fewer seeds and fig wasp offspring. Our field
      experiments with Ficushispida, a dioecious fig tree, examined how the length of
      time that receptive figs have remained un-pollinated influences the behaviour and
      reproductive success of its short-lived fig wasp pollinator, Ceratosolensolmsi
      marchali. The results were consistent in three different seasons, and on male and
      female trees, although receptivity was greatly extended during colder months.
      Pollinators took longer to find the ostioles of older figs, and longer to
      penetrate them. They also became increasingly unwilling to enter figs as they
      aged, and increasing numbers of the wasps became trapped in the ostiolar bracts.
      Larger individuals were particularly unwilling to enter older figs, resulting in
      older figs being pollinated by smaller wasps. On female trees, where figs produce
      only seeds, seed production declined rapidly with fig age. On male trees, the
      numbers and size of fig wasp offspring declined, and a higher proportion were
      male. Older male figs are harder to enter, especially for larger individuals, and
      offer poorer quality oviposition opportunities. This study opens an interesting
      new perspective on the coevolution of figs and their pollinators, especially
      factors influencing pollinator body size and emphasises the subtleties of
      interactions between mutualists. 

PMID- 24086316
TI  - Anatomically asymmetrical runners move more asymmetrically at the same metabolic
      cost.
AB  - We hypothesized that, as occurring in cars, body structural asymmetries could
      generate asymmetry in the kinematics/dynamics of locomotion, ending up in a
      higher metabolic cost of transport, i.e. more 'fuel' needed to travel a given
      distance. Previous studies found the asymmetries in horses' body negatively
      correlated with galloping performance. In this investigation, we analyzed
      anatomical differences between the left and right lower limbs as a whole by
      performing 3D cross-correlation of Magnetic Resonance Images of 19 male runners,
      clustered as Untrained Runners, Occasional Runners and Skilled Runners. Running
      kinematics of their body centre of mass were obtained from the body segments
      coordinates measured by a 3D motion capture system at incremental running
      velocities on a treadmill. A recent mathematical procedure quantified the
      asymmetry of the body centre of mass trajectory between the left and right steps.
      During the same sessions, runners' metabolic consumption was measured and the
      cost of transport was calculated. No correlations were found between
      anatomical/kinematic variables and the metabolic cost of transport, regardless of
      the training experience. However, anatomical symmetry significant correlated to
      the kinematic symmetry, and the most trained subjects showed the highest level of
      kinematic symmetry during running. Results suggest that despite the significant
      effects of anatomical asymmetry on kinematics, either those changes are too small
      to affect economy or some plastic compensation in the locomotor system mitigates
      the hypothesized change in energy expenditure of running. 

PMID- 24086317
TI  - Increased ventral striatal volume in college-aged binge drinkers.
AB  - BACKGROUND: Binge drinking is a serious public health issue associated with
      cognitive, physiological, and anatomical differences from healthy individuals. No
      studies, however, have reported subcortical grey matter differences in this
      population. To address this, we compared the grey matter volumes of college-age
      binge drinkers and healthy controls, focusing on the ventral striatum,
      hippocampus and amygdala. METHOD: T1-weighted images of 19 binge drinkers and 19
      healthy volunteers were analyzed using voxel-based morphometry. Structural data
      were also covaried with Alcohol Use Disorders Identification Test (AUDIT) scores.
      Cluster-extent threshold and small volume corrections were both used to analyze
      imaging data. RESULTS: Binge drinkers had significantly larger ventral striatal
      grey matter volumes compared to controls. There were no between group differences
      in hippocampal or amygdalar volume. Ventral striatal, amygdalar, and hippocampal
      volumes were also negatively related to AUDIT scores across groups. CONCLUSIONS:
      Our findings stand in contrast to the lower ventral striatal volume previously
      observed in more severe forms of alcohol use disorders, suggesting that college
      age binge drinkers may represent a distinct population from those groups. These
      findings may instead represent early sequelae, compensatory effects of repeated
      binge and withdrawal, or an endophenotypic risk factor.

PMID- 24086318
TI  - Development of a reference standard of Escherichia coli DNA for residual DNA
      determination in China.
AB  - This collaborative study developed the first national Escherichia coli (E. coli)
      DNA reference standard for standardizing quantitative residual DNA assay methods,
      fluorescence dye (PicoGreen) and quantitative PCR (q-PCR), which were widely
      employed to measure residual DNA contents of prokaryotic-derived recombinant
      products. High purity of E. coli strain BL21 was extracted by the cetyl triethyl
      ammonium bromide (CTAB)/phenol chloroform method, analyzed by UV-visible
      spectrophotometry and electrophoresis, diluted with tris-EDTA (TE) buffer and
      manually dispensed. Then, with a cooperative calibration among six laboratories,
      including five manufacturers and one national control laboratory, the
      concentration of E. coli DNA standard solution was determined as 96.2 MUg/mL (95%
      C.I: 95.5-96.9 MUg/mL, CV 3.4%). The candidate showed excellent stability both
      from accelerated degradation study and real time stability study. The
      applicability study showed that the E. coli DNA reference could reach the
      sensitivity of 0.781 ng/mL and 1 fg/MUL, respectively, in fluorescent dye and q
      PCR assay, and also had good linearity and precision. The consistency of the
      reference could meet the requirements of the national reference standard. As a
      conclusion, the candidate material was suitable to serve as a China national
      standard for E. coli residual DNA determination. The successful establishment of
      the E. coli DNA standard will facilitate the standardization of quantitative
      methods for testing residual host cell DNA. 

PMID- 24086319
TI  - Cotrimoxazole prophylaxis and risk of severe anemia or severe neutropenia in
      HAART-exposed, HIV-uninfected infants.
AB  - BACKGROUND: Prophylactic cotrimoxazole is recommended for infants born to HIV
      infected mothers. However, cotrimoxazole may increase the risk of severe anemia
      or neutropenia. METHODS: We compared the proportion of HIV-exposed uninfected
      (HIV-EU) infants experiencing incident severe anemia (and separately, severe
      neutropenia) between a prospective cohort receiving prophylactic cotrimoxazole
      from 1 to 6 months vs. infants from two prior trials who did not receive
      cotrimoxazole. Infants were from rural and urban communities in southern
      Botswana. RESULTS: A total of 1705 HIV-EU infants were included. Among these 645
      (37.8%) were fed with iron-supplemented formula from birth. Severe anemia
      developed in 87 (5.1%) infants, and severe neutropenia in 164 (9.6%) infants. In
      an analysis stratified by infant feeding method, there were no significant
      differences in the risk of severe anemia by prophylactic cotrimoxazole exposure
      risk difference, -0.69% (95% confidence interval [CI] -2.1 to 0.76%). Findings
      were similar in multivariable analysis, adjusted odds ratio (aOR) 0.35 (95% CI
      0.07 to 1.65). There were also no significant differences observed for severe
      neutropenia by cotrimoxazole exposure, risk difference 2.0% (95% CI -1.3 to 5.2%)
      and aOR 0.80 (95% CI 0.33 to 1.93). CONCLUSIONS: Severe anemia and severe
      neutropenia were infrequent among HIV-exposed uninfected infants receiving
      cotrimoxazole from 1-6 months of age. Concerns regarding hematologic toxicity
      should not limit the use of prophylactic cotrimoxazole in HIV-exposed uninfected
      infants. CLINICALTRIAL.SGOV REGISTRATION NUMBERS: NCT01086878
      (http://clinicaltrials.gov/show/NCT01086878), NCT00197587
      (http://clinicaltrials.gov/show/NCT00197587), and NCT00270296
      (http://clinicaltrials.gov/show/NCT00270296).

PMID- 24086320
TI  - Bayesian parameter inference by Markov chain Monte Carlo with hybrid fitness
      measures: theory and test in apoptosis signal transduction network.
AB  - When model parameters in systems biology are not available from experiments, they
      need to be inferred so that the resulting simulation reproduces the
      experimentally known phenomena. For the purpose, Bayesian statistics with Markov
      chain Monte Carlo (MCMC) is a useful method. Conventional MCMC needs likelihood
      to evaluate a posterior distribution of acceptable parameters, while the
      approximate Bayesian computation (ABC) MCMC evaluates posterior distribution with
      use of qualitative fitness measure. However, none of these algorithms can deal
      with mixture of quantitative, i.e., likelihood, and qualitative fitness measures
      simultaneously. Here, to deal with this mixture, we formulated Bayesian formula
      for hybrid fitness measures (HFM). Then we implemented it to MCMC (MCMC-HFM). We
      tested MCMC-HFM first for a kinetic toy model with a positive feedback. Inferring
      kinetic parameters mainly related to the positive feedback, we found that MCMC
      HFM reliably infer them using both qualitative and quantitative fitness measures.
      Then, we applied the MCMC-HFM to an apoptosis signal transduction network
      previously proposed. For kinetic parameters related to implicit positive
      feedbacks, which are important for bistability and irreversibility of the output,
      the MCMC-HFM reliably inferred these kinetic parameters. In particular, some
      kinetic parameters that have experimental estimates were inferred without using
      these data and the results were consistent with experiments. Moreover, for some
      parameters, the mixed use of quantitative and qualitative fitness measures
      narrowed down the acceptable range of parameters. 

PMID- 24086321
TI  - Streptochlorin suppresses allergic dermatitis and mast cell activation via
      regulation of Lyn/Fyn and Syk signaling pathways in cellular and mouse models.
AB  - Allergic diseases are chronic inflammatory conditions with specific immune and
      inflammatory mechanisms. Scientific interest in understanding the mechanisms and
      discovering novel agents for the prevention and treatment of allergic disease is
      increasing. Streptochlorin, a small compound derived from marine actinomycete
      possesses anti-angiogenic and anti-tumor activities. However, the anti-allergic
      effects and underlying mechanisms remain to be elucidated. In the present study,
      we investigated the effect of streptochlorin on allergic responses in vitro and
      in vivo. Streptochlorin inhibited degranulation and production of tumor necrosis
      factor-alpha and IL-4 by antigen-stimulated mast cells. Streptochlorin also
      inhibited the phosphorylation of Akt and the mitogen-activated protein kinases
      (MAPKs), including p38, ERK, and JNK. Further, streptochlorin reduced the
      phosphorylation of Syk in RBL-2H3 cells and inhibited the activity of Lyn and
      Fyn. Furthermore, administration of streptochlorin suppressed the allergic
      reactions in both passive cutaneous anaphylaxis reaction and 2, 4
      dinitrofluorobenzene (DNFB)-induced allergic dermatitis in mice model.
      Considering the data obtained, we report for the first time that streptochlorin
      possess anti-allergic properties. The underlying mechanism of streptochlorin in
      exhibiting potent anti-allergic activity might be through the inhibition of the
      Lyn/Fyn and Syk signaling pathways. 

PMID- 24086322
TI  - Genetic and morphological divergences in the cosmopolitan deep-sea amphipod
      Eurythenes gryllus reveal a diverse abyss and a bipolar species.
AB  - Eurythenes gryllus is one of the most widespread amphipod species, occurring in
      every ocean with a depth range covering the bathyal, abyssal and hadal zones.
      Previous studies, however, indicated the existence of several genetically and
      morphologically divergent lineages, questioning the assumption of its
      cosmopolitan and eurybathic distribution. For the first time, its genetic
      diversity was explored at the global scale (Arctic, Atlantic, Pacific and
      Southern oceans) by analyzing nuclear (28S rDNA) and mitochondrial (COI, 16S
      rDNA) sequence data using various species delimitation methods in a
      phylogeographic context. Nine putative species-level clades were identified
      within E. gryllus. A clear distinction was observed between samples collected at
      bathyal versus abyssal depths, with a genetic break occurring around 3,000 m. Two
      bathyal and two abyssal lineages showed a widespread distribution, while five
      other abyssal lineages each seemed to be restricted to a single ocean basin. The
      observed higher diversity in the abyss compared to the bathyal zone stands in
      contrast to the depth-differentiation hypothesis. Our results indicate that,
      despite the more uniform environment of the abyss and its presumed lack of
      obvious isolating barriers, abyssal populations might be more likely to show
      population differentiation and undergo speciation events than previously assumed.
      Potential factors influencing species' origins and distributions, such as
      hydrostatic pressure, are discussed. In addition, morphological findings
      coincided with the molecular clades. Of all specimens available for examination,
      those of the bipolar bathyal clade seemed the most similar to the 'true' E.
      gryllus. We present the first molecular evidence for a bipolar distribution in a
      macro-benthic deep-sea organism. 

PMID- 24086323
TI  - Radiotherapy plus concurrent or sequential temozolomide for glioblastoma in the
      elderly: a meta-analysis.
AB  - BACKGROUND: Many physicians are reluctant to treat elderly glioblastoma (GBM)
      patients as aggressively as younger patients, which is not evidence based due to
      the absence of validated data from primary studies. We conducted a meta-analysis
      to provide valid evidence for the use of the aggressive combination of
      radiotherapy (RT) and temozolomide (TMZ) in elderly GBM patients. METHODS: A
      systematic literature search was conducted using the PubMed, EMBASE and Cochrane
      databases. Studies comparing combined RT/TMZ with RT alone in elderly patients
      (>=65 years) with newly diagnosed GBM were eligible for inclusion. RESULTS: No
      eligible randomized trials were identified. Alternatively, a meta-analysis of
      nonrandomized studies (NRSs) was performed, with 16 studies eligible for overall
      survival (OS) analysis and nine for progression-free survival (PFS) analysis.
      Combined RT/TMZ was shown to reduce the risk of death and progression in elderly
      GBM patients compared with RT alone (OS hazard ratio [HR] 0.59, 95% confidence
      interval [CI] 0.48-0.72; PFS: HR 0.58, 95% CI 0.41-0.84). Evaluable patients were
      reported to tolerate combined treatment but certain toxicities, and especially
      hematological toxicities, were more frequently observed. Limited data on O6
      methylguanine-DNA methyltransferase (MGMT) promoter status and quality of life
      were reported. CONCLUSION: The meta-analysis of NRSs provided level 2a evidence
      (Oxford Centre for Evidence-Based Medicine) that combined RT/TMZ conferred a
      clear survival benefit on a selection of elderly GBM patients who had a favorable
      prognosis (e.g., extensive resection, favorable KPS). Toxicities were more
      frequent but acceptable. Future randomized trials are warranted to justify a
      definitive conclusion.

PMID- 24086324
TI  - Eeyore: a novel mouse model of hereditary deafness.
AB  - Animal models that recapitulate human disease are proving to be an invaluable
      tool in the identification of novel disease-associated genes. These models can
      improve our understanding of the complex genetic mechanisms involved in disease
      and provide a basis to guide therapeutic strategies to combat these conditions.
      We have identified a novel mouse model of non-syndromic sensorineural hearing
      loss with linkage to a region on chromosome 18. Eeyore mutant mice have early
      onset progressive hearing impairment and show abnormal structure of the sensory
      epithelium from as early as 4 weeks of age. Ultrastructural and histological
      analyses show irregular hair cell structure and degeneration of the sensory hair
      bundles in the cochlea. The identification of new genes involved in hearing is
      central to understanding the complex genetic pathways involved in the hearing
      process and the loci at which these pathways are interrupted in people with a
      genetic hearing loss. We therefore discuss possible candidate genes within the
      linkage region identified in eeyore that may underlie the deafness phenotype in
      these mice. Eeyore provides a new model of hereditary sensorineural deafness and
      will be an important tool in the search for novel deafness genes. 

PMID- 24086326
TI  - Gene regulatory networks elucidating huanglongbing disease mechanisms.
AB  - Next-generation sequencing was exploited to gain deeper insight into the response
      to infection by Candidatus liberibacter asiaticus (CaLas), especially the immune
      disregulation and metabolic dysfunction caused by source-sink disruption.
      Previous fruit transcriptome data were compared with additional RNA-Seq data in
      three tissues: immature fruit, and young and mature leaves. Four categories of
      orchard trees were studied: symptomatic, asymptomatic, apparently healthy, and
      healthy. Principal component analysis found distinct expression patterns between
      immature and mature fruits and leaf samples for all four categories of trees. A
      predicted protein - protein interaction network identified HLB-regulated genes
      for sugar transporters playing key roles in the overall plant responses. Gene set
      and pathway enrichment analyses highlight the role of sucrose and starch
      metabolism in disease symptom development in all tissues. HLB-regulated genes
      (glucose-phosphate-transporter, invertase, starch-related genes) would likely
      determine the source-sink relationship disruption. In infected leaves,
      transcriptomic changes were observed for light reactions genes (downregulation),
      sucrose metabolism (upregulation), and starch biosynthesis (upregulation). In
      parallel, symptomatic fruits over-expressed genes involved in photosynthesis,
      sucrose and raffinose metabolism, and downregulated starch biosynthesis. We
      visualized gene networks between tissues inducing a source-sink shift. CaLas
      alters the hormone crosstalk, resulting in weak and ineffective tissue-specific
      plant immune responses necessary for bacterial clearance. Accordingly, expression
      of WRKYs (including WRKY70) was higher in fruits than in leaves. Systemic
      acquired responses were inadequately activated in young leaves, generally
      considered the sites where most new infections occur. 

PMID- 24086325
TI  - From 'omics to otoliths: responses of an estuarine fish to endocrine disrupting
      compounds across biological scales.
AB  - Endocrine disrupting chemicals (EDCs) cause physiological abnormalities and
      population decline in fishes. However, few studies have linked environmental EDC
      exposures with responses at multiple tiers of the biological hierarchy, including
      population-level effects. To this end, we undertook a four-tiered investigation
      in the impacted San Francisco Bay estuary with the Mississippi silverside
      (Menidia audens), a small pelagic fish. This approach demonstrated links between
      different EDC sources and fish responses at different levels of biological
      organization. First we determined that water from a study site primarily impacted
      by ranch run-off had only estrogenic activity in vitro, while water sampled from
      a site receiving a combination of urban, limited ranch run-off, and treated
      wastewater effluent had both estrogenic and androgenic activity. Secondly, at the
      molecular level we found that fish had higher mRNA levels for estrogen-responsive
      genes at the site where only estrogenic activity was detected but relatively
      lower expression levels where both estrogenic and androgenic EDCs were detected.
      Thirdly, at the organism level, males at the site exposed to both estrogens and
      androgens had significantly lower mean gonadal somatic indices, significantly
      higher incidence of severe testicular necrosis and altered somatic growth
      relative to the site where only estrogens were detected. Finally, at the
      population level, the sex ratio was significantly skewed towards males at the
      site with measured androgenic and estrogenic activity. Our results suggest that
      mixtures of androgenic and estrogenic EDCs have antagonistic and potentially
      additive effects depending on the biological scale being assessed, and that
      mixtures containing androgens and estrogens may produce unexpected effects. In
      summary, evaluating EDC response at multiple tiers is necessary to determine the
      source of disruption (lowest scale, i.e. cell line) and what the ecological
      impact will be (largest scale, i.e. sex ratio). 

PMID- 24086328
TI  - High performance of histidine-rich protein 2 based rapid diagnostic tests in
      French Guiana are explained by the absence of pfhrp2 gene deletion in P.
      falciparum.
AB  - BACKGROUND: Care for malaria patients in endemic areas has been improved through
      the increasing use of Rapid Diagnostic Tests (RDTs). Most RDTs target the
      histidine-rich protein-2 antigen (PfHRP2) to detect P. falciparum, as it is
      abundant and shows great heat stability. However, their use in South America has
      been widely questioned following a recent publication that pinpoints the high
      prevalence of Peruvian field isolates lacking the gene encoding this protein. In
      the remote rural health centers of French Guiana, RDTs are the main diagnosis
      tools. Therefore, a study of PfHRP2 RDT performances and pfhrp2 genotyping was
      conducted to determine whether a replacement of the current pLDH-based kit could
      be considered. METHODS: The performance study compared the SD Malaria Ag test
      P.f/Pan(r) kit with the current gold standard diagnosis by microscopy. The
      prevalence of pfhrp2 and pfhrp3 deletions were evaluated from 221 P. falciparum
      isolates collected between 2009 and 2011 in French Guiana. RESULTS: Between
      January 2010 and August 2011, 960 suspected cases of malaria were analyzed using
      microscopy and RDTs. The sensitivity of the SD Malaria Ag test P.f/Pan(r) for
      detection of P. falciparum was 96.8% (95% CI: 90.9-99.3), and 86.0% (95% CI: 78.9
      91.5) for the detection of P. vivax. No isolates (95% CI: 0-4.5) lacking either
      exon of the pfhrp2 gene were identified among the 221 P. falciparum isolates
      analyzed, but 7.4% (95% CI: 2.8-15.4) lacked the exon 2 part of the pfhrp3 gene.
      CONCLUSIONS: Field isolates lacking either exon of the pfhrp2 gene are absent in
      this western part of South America. Despite its sensibility to detect P. vivax,
      the SD Malaria Ag test P.f/Pan(r) kit is a satisfying alternative to microscopy
      in remote health centers, where it is difficult to provide highly skilled
      microscopists and to maintain the necessary equipment.

PMID- 24086327
TI  - The worldwide association between television viewing and obesity in children and
      adolescents: cross sectional study.
AB  - BACKGROUND: Studies exploring the effect of television viewing on obesity
      throughout childhood are conflicting. Most studies have been confined to single
      high-income countries. Our aim was to examine the association between television
      viewing habits and Body Mass Index (BMI) in adolescents and children in a
      multicentre worldwide sample. METHODS: In the International Study of Asthma and
      Allergies in Children Phase Three, adolescents aged between 12 and 15 years
      completed questionnaires which included questions on television viewing habits,
      height and weight. Parents/guardians of children aged between 5 and 8 years
      completed the same questionnaire on behalf of their children. The questionnaire
      asked "During a normal week, how many hours a day (24 hours) do you (does your
      child) watch television?" Responses were categorised as; "short" (<1 hour),
      "moderate" (1 to <=3 hours), "long" (3 to <=5 hours) and "prolonged" (>5 hours).
      FINDINGS: 207,672 adolescents from 37 countries and 77,003 children from 18
      countries provided data. Daily television viewing in excess of one hour was
      reported in 89% of adolescents and 79% of children. Compared with adolescents in
      the short viewing group, those in the moderate, long and prolonged groups had
      BMIs that were 0.14 kg/m(2), 0.21 kg/m(2), 0.30 kg/m(2) and 0.08 kg/m(2), 0.16
      kg/m(2) and 0.17 kg/m(2) larger for females and males respectively (both
      P<0.001). Compared with children in the short viewing group, those in the
      moderate, long and prolonged groups had BMIs that were 0.24 kg/m(2), 0.34
      kg/m(2), 0.36 kg/m(2) and 0.19 kg/m(2), 0.32 kg/m(2) and 0.36 kg/m(2) larger for
      females and males respectively (both P<0.001). INTERPRETATION: Increased
      television viewing hours were positively associated with BMI in both adolescents
      and children with an apparent dose response effect. These findings extend the
      evidence that television viewing contributes to increased BMI in childhood.

PMID- 24086329
TI  - The mechanism of methylated seed oil on enhancing biological efficacy of
      topramezone on weeds.
AB  - Methylated seed oil (MSO) is a recommended adjuvant for the newly registered
      herbicide topramezone in China and also in other countries of the world, but the
      mechanism of MSO enhancing topramezone efficacy is still not clear. Greenhouse
      and laboratory experiments were conducted to determine the effects of MSO on
      efficacy, solution property, droplet spread and evaporation, active ingredient
      deposition, foliar absorption and translocation of topramezone applied to giant
      foxtail (Setaria faberi Herrm.) and velvetleaf (Abutilon theophrasti Medic.).
      Experimental results showed that 0.3% MSO enhanced the efficacy of topramezone by
      1.5-fold on giant foxtail and by 1.0-fold on velvetleaf. When this herbicide was
      mixed with MSO, its solution surface tension and leaf contact angle decreased
      significantly, its spread areas on weed leaf surfaces increased significantly,
      its wetting time was shortened on giant foxtail but not changed on velvetleaf,
      and less of its active ingredient crystal was observed on the treated weed leaf
      surfaces. MSO increased the absorption of topramezone by 68.9% for giant foxtail
      and by 45.9% for velvetleaf 24 hours after treatment. It also apparently promoted
      the translocation of this herbicide in these two weeds. 

PMID- 24086330
TI  - Selectivity and plasticity in a sound-evoked male-male interaction in Drosophila.
AB  - During courtship, many animals, including insects, birds, fish, and mammals,
      utilize acoustic signals to transmit information about species identity. Although
      auditory communication is crucial across phyla, the neuronal and physiologic
      processes are poorly understood. Sound-evoked chaining behavior, a display of
      homosexual courtship behavior in Drosophila males, has long been used as an
      excellent model for analyzing auditory behavior responses, outcomes of acoustic
      perception and higher-order brain functions. Here we developed a new method,
      termed ChaIN (Chain Index Numerator), in which we use a computer-based auto
      detection system for chaining behavior. The ChaIN system can systematically
      detect the chaining behavior induced by a series of modified courtship song
      playbacks. Two evolutionarily related Drosophila species, Drosophila melanogaster
      and Drosophila simulans, exhibited dramatic selective increases in chaining
      behavior when exposed to specific auditory cues, suggesting that auditory
      discrimination processes are involved in the acceleration of chaining behavior.
      Prolonged monotonous pulse sounds containing courtship song components also
      induced high intense chaining behavior. Interestingly, the chaining behavior was
      gradually suppressed over time when song playback continued. This behavioral
      change is likely to be a plastic behavior and not a simple sensory adaptation or
      fatigue, because the suppression was released by applying a different pulse
      pattern. This behavioral plasticity is not a form of habituation because
      different modality stimuli did not recover the behavioral suppression.
      Intriguingly, this plastic behavior partially depended on the cAMP signaling
      pathway controlled by the rutabaga adenylyl cyclase gene that is important for
      learning and memory. Taken together, this study demonstrates the selectivity and
      behavioral kinetics of the sound-induced interacting behavior of Drosophila
      males, and provides a basis for the systematic analysis of genes and neural
      circuits underlying complex acoustic behavior. 

PMID- 24086331
TI  - Parasitization by Cotesia chilonis influences gene expression in fatbody and
      hemocytes of Chilo suppressalis.
AB  - BACKGROUND: During oviposition many parasitoid wasps inject various factors, such
      as polydnaviruses (PDVs), along with eggs that manipulate the physiology and
      development of their hosts. These manipulations are thought to benefit the
      parasites. However, the detailed mechanisms of insect host-parasitoid
      interactions are not fully understood at the molecular level. Based on recent
      findings that some parasitoids influence gene expression in their hosts, we posed
      the hypothesis that parasitization by a braconid wasp, Cotesia chilonis,
      influences the expression of genes responsible for development, metabolism and
      immune functions in the fatbody and hemocytes of its host, Chilo suppressalis.
      METHODOLOGY/PRINCIPAL FINDINGS: We obtained 39,344,452 reads, which were
      assembled into 146,770 scaffolds, and 76,016 unigenes. Parasitization impacted
      gene expression in fatbody and hemocytes. Of these, 8096 fatbody or 5743 hemocyte
      unigenes were down-regulated, and 2572 fatbody or 1452 hemocyte unigenes were up
      regulated. Gene ontology data showed that the majority of the differentially
      expressed genes are involved in enzyme-regulated activity, binding, transcription
      regulator activity and catalytic activity. qPCR results show that most anti
      microbial peptide transcription levels were up-regulated after parasitization.
      Expression of bracovirus genes was detected in parasitized larvae with 19 unique
      sequences identified from six PDV gene families including ankyrin, CrV1 protein,
      cystatin, early-expressed (EP) proteins, lectin, and protein tyrosine
      phosphatase. CONCLUSIONS: The current study supports our hypothesis that
      parasitization influences the expression of fatbody and hemocyte genes in the
      host, C. suppressalis. The general view is that manipulation of host metabolism
      and immunity benefits the development and emergence of the parasitoid offsprings.
      The accepted beneficial mechanisms include the direct impact of parasitoid
      associated virulence factors such as venom and polydnavirus on host tissues (such
      as cell damage) and, more deeply, the ability of these factors to influence gene
      expression. We infer that insect parasitoids generally manipulate their
      environments, the internal milieu of their hosts.

PMID- 24086332
TI  - Detecting rare variants in case-parents association studies.
AB  - Despite the success of genome-wide association studies (GWASs) in detecting
      common variants (minor allele frequency >=0.05) many suggested that rare variants
      also contribute to the genetic architecture of diseases. Recently, researchers
      demonstrated that rare variants can show a strong stratification which may not be
      corrected by using existing methods. In this paper, we focus on a case-parents
      study and consider methods for testing group-wise association between multiple
      rare (and common) variants in a gene region and a disease. All tests depend on
      the numbers of transmitted mutant alleles from parents to their diseased children
      across variants and hence they are robust to the effect of population
      stratification. We use extensive simulation studies to compare the performance of
      four competing tests: the largest single-variant transmission disequilibrium test
      (TDT), multivariable test, combined TDT, and a likelihood ratio test based on a
      random-effects model. We find that the likelihood ratio test is most powerful in
      a wide range of settings and there is no negative impact to its power performance
      when common variants are also included in the analysis. If deleterious and
      protective variants are simultaneously analyzed, the likelihood ratio test was
      generally insensitive to the effect directionality, unless the effects are
      extremely inconsistent in one direction. 

PMID- 24086333
TI  - Safety, adherence and acceptability of intermittent tenofovir/emtricitabine as
      HIV pre-exposure prophylaxis (PrEP) among HIV-uninfected Ugandan volunteers
      living in HIV-serodiscordant relationships: a randomized, clinical trial.
AB  - BACKGROUND: Efficacy of oral pre-exposure prophylaxis (PrEP) in prevention of HIV
      acquisition has been evaluated using a daily regimen. However, adherence to long
      term daily medication is rarely perfect. Intermittent regimen may be a feasible
      alternative. Preclinical studies have demonstrated effectiveness of intermittent
      PrEP in SHIV prevention among animals. However, little is known about
      intermittent PrEP regimens. DESIGN: Seventy two HIV-uninfected volunteers in HIV
      serodiscordant couple relationships in Uganda were randomly assigned to receive
      daily oral Tenofovir/Emtricitabine (TDF/FTC-Truvada) or placebo, or intermittent
      (Monday, Friday and within 2 hours after sex, not to exceed one dose per day)
      oral TDF/FTC or placebo in a 2:1:2:1 ratio. Volunteers and study staff were
      blinded to drug assignment, but not to regimen assignment. METHODS: Volunteers
      were followed for 4 months after randomization, with monthly clinical and
      laboratory safety assessments and comprehensive HIV risk reduction services.
      Adherence was monitored using medication event monitoring system (MEMS) and self
      report. Sexual activity data were collected via daily short text message (SMS)
      and self-report. HIV-specific immune responses were assessed by IFN-gamma
      ELISPOT. RESULTS: Both daily and intermittent oral TDF/FTC regimens were well
      tolerated. Median MEMS adherence rates were 98% (IQR: 93-100) for daily PrEP
      regimen, 91% (IQR: 73-97) for fixed intermittent dosing and 45% (IQR: 20-63) for
      post-coital dosing. SMS response rate was 74%, but increased to 80% after
      excluding server outages; results may have been affected by the novelty of this
      measure. The majority of volunteers expressed willingness with no particular
      preference for either regimen. CONCLUSIONS: Both daily and intermittent oral PrEP
      dosing regimens were safe. Adherence was high for daily and fixed intermittent
      dosing; post-coital dosing was associated with poor adherence. Fixed intermittent
      PrEP regimens may be feasible especially if a minimum effective drug
      concentration correlating with HIV prevention can be achieved with this dosing.
      REGISTRATION: Clinicaltrials.gov number NCT00931346.

PMID- 24086334
TI  - A single dose of azithromycin does not improve clinical outcomes of children
      hospitalised with bronchiolitis: a randomised, placebo-controlled trial.
AB  - OBJECTIVE: Bronchiolitis, one of the most common reasons for hospitalisation in
      young children, is particularly problematic in Indigenous children. Macrolides
      may be beneficial in settings where children have high rates of nasopharyngeal
      bacterial carriage and frequent prolonged illness. The aim of our double-blind
      placebo-controlled randomised trial was to determine if a large single dose of
      azithromycin (compared to placebo) reduced length of stay (LOS), duration of
      oxygen (O2) and respiratory readmissions within 6 months of children hospitalised
      with bronchiolitis. We also determined the effect of azithromycin on
      nasopharyngeal microbiology. METHODS: Children aged <=18 months were randomised
      to receive a single large dose (30 mg/kg) of either azithromycin or placebo
      within 24 hrs of hospitalisation. Nasopharyngeal swabs were collected at baseline
      and 48 hrs later. Primary endpoints (LOS, O2) were monitored every 12 hrs.
      Hospitalised respiratory readmissions 6-months post discharge was collected.
      RESULTS: 97 children were randomised (n = 50 azithromycin, n = 47 placebo).
      Median LOS was similar in both groups; azithromycin = 54 hours, placebo = 58
      hours (difference between groups of 4 hours 95%CI -8, 13, p = 0.6). O2
      requirement was not significantly different between groups; Azithromycin = 35
      hrs; placebo = 42 hrs (difference 7 hours, 95%CI -9, 13, p = 0.7). Number of
      children re-hospitalised was similar 10 per group (OR = 0.9, 95%CI 0.3, 2, p =
      0.8). At least one virus was detected in 74% of children. The azithromycin group
      had reduced nasopharyngeal bacterial carriage (p = 0.01) but no difference in
      viral detection at 48 hours. CONCLUSION: Although a single dose of azithromycin
      reduces carriage of bacteria, it is unlikely to be beneficial in reducing LOS,
      duration of O2 requirement or readmissions in children hospitalised with
      bronchiolitis. It remains uncertain if an earlier and/or longer duration of
      azithromycin improves clinical and microbiological outcomes for children. The
      trial was registered with the Australian and New Zealand Clinical Trials
      Register. Clinical trials number: ACTRN12608000150347.
      http://www.anzctr.org.au/TrialSearch.aspx.

PMID- 24086335
TI  - Ribosomal S6 Kinase 2 (RSK2) maintains genomic stability by activating the
      Atm/p53-dependent DNA damage pathway.
AB  - Ribosomal S6 Kinase 2 (RSK2) is a member of the p90(RSK) family of
      serine/threonine kinases, which are widely expressed and respond to many growth
      factors, peptide hormones, and neurotransmitters. Loss-of function mutations in
      the RPS6KA3 gene, which encodes the RSK2 protein, have been implicated in Coffin
      Lowry Syndrome (CLS), an X-linked mental retardation disorder associated with
      cognitive deficits and behavioral impairments. However, the cellular and
      molecular mechanisms underlying this neurological disorder are not known. Recent
      evidence suggests that defective DNA damage signaling might be associated with
      neurological disorders, but the role of RSK2 in the DNA damage pathway remains to
      be elucidated. Here, we show that Adriamycin-induced DNA damage leads to the
      phosphorylation of RSK2 at Ser227 and Thr577 in the chromatin fraction, promotes
      RSK2 nuclear translocation, and enhances RSK2 and Atm interactions in the nuclear
      fraction. Furthermore, using RSK2 knockout mouse fibroblasts and RSK2-deficient
      cells from CLS patients, we demonstrate that ablation of RSK2 impairs the
      phosphorylation of Atm at Ser1981 and the phosphorylation of p53 at Ser18 (mouse)
      or Ser15 (human) in response to genotoxic stress. We also show that RSK2 affects
      p53-mediated downstream cellular events in response to DNA damage, that RSK2
      knockout relieves cell cycle arrest at the G2/M phase, and that an increased
      number of gammaH2AX foci, which are associated with defects in DNA repair, are
      present in RSK2-deficient cells. Taken together, our findings demonstrated that
      RSK2 plays an important role in the DNA damage pathway that maintains genomic
      stability by mediating cell cycle progression and DNA repair. 

PMID- 24086336
TI  - Plasma lipid profiling shows similar associations with prediabetes and type 2
      diabetes.
AB  - The relationship between lipid metabolism with prediabetes (impaired fasting
      glucose and impaired glucose tolerance) and type 2 diabetes mellitus is poorly
      defined. We hypothesized that a lipidomic analysis of plasma lipids might improve
      the understanding of this relationship. We performed lipidomic analysis measuring
      259 individual lipid species, including sphingolipids, phospholipids,
      glycerolipids and cholesterol esters, on fasting plasma from 117 type 2 diabetes,
      64 prediabetes and 170 normal glucose tolerant participants in the Australian
      Diabetes, Obesity and Lifestyle Study (AusDiab) then validated our findings on
      1076 individuals from the San Antonio Family Heart Study (SAFHS). Logistic
      regression analysis of identified associations with type 2 diabetes (135 lipids)
      and prediabetes (134 lipids), after adjusting for multiple covariates. In
      addition to the expected associations with diacylglycerol, triacylglycerol and
      cholesterol esters, type 2 diabetes and prediabetes were positively associated
      with ceramide, and its precursor dihydroceramide, along with
      phosphatidylethanolamine, phosphatidylglycerol and phosphatidylinositol.
      Significant negative associations were observed with the ether-linked
      phospholipids alkylphosphatidylcholine and alkenylphosphatidylcholine. Most of
      the significant associations in the AusDiab cohort (90%) were subsequently
      validated in the SAFHS cohort. The aberration of the plasma lipidome associated
      with type 2 diabetes is clearly present in prediabetes, prior to the onset of
      type 2 diabetes. Lipid classes and species associated with type 2 diabetes
      provide support for a number of existing paradigms of dyslipidemia and suggest
      new avenues of investigation. 

PMID- 24086338
TI  - Steady as he goes: at-sea movement of adult male Australian sea lions in a
      dynamic marine environment.
AB  - The southern coastline of Australia forms part of the worlds' only northern
      boundary current system. The Bonney Upwelling occurs every austral summer along
      the south-eastern South Australian coastline, a region that hosts over 80% of the
      worlds population of an endangered endemic otariid, the Australian sea lion. We
      present the first data on the movement characteristics and foraging behaviour of
      adult male Australian sea lions across their South Australian range. Synthesizing
      telemetric, oceanographic and isotopic datasets collected from seven individuals
      enabled us to characterise individual foraging behaviour over an approximate two
      year time period. Data suggested seasonal variability in stable carbon and
      nitrogen isotopes that could not be otherwise explained by changes in animal
      movement patterns. Similarly, animals did not change their foraging patterns
      despite fine-scale spatial and temporal variability of the upwelling event.
      Individual males tended to return to the same colony at which they were tagged
      and utilized the same at-sea regions for foraging irrespective of oceanographic
      conditions or time of year. Our study contrasts current general assumptions that
      male otariid life history strategies should result in greater dispersal, with
      adult male Australian sea lions displaying central place foraging behaviour
      similar to males of other otariid species in the region. 

PMID- 24086337
TI  - Undifferentiated and differentiated PC12 cells protected by huprines against
      injury induced by hydrogen peroxide.
AB  - Oxidative stress is implicated in the pathogenesis of neurodegenerative disorders
      and hydrogen peroxide (H2O2) plays a central role in the stress. Huprines, a
      group of potent acetylcholinesterase inhibitors (AChEIs), have shown a broad
      cholinergic pharmacological profile. Recently, it has been observed that huprine
      X (HX) improves cognition in non transgenic middle aged mice and shows a
      neuroprotective activity (increased synaptophysin expression) in 3xTg-AD mice.
      Consequently, in the present experiments the potential neuroprotective effect of
      huprines (HX, HY, HZ) has been analyzed in two different in vitro conditions:
      undifferentiated and NGF-differentiated PC12 cells. Cells were subjected to
      oxidative insult (H2O2, 200 uM) and the protective effects of HX, HY and HZ (0.01
      uM-1 uM) were analyzed after a pre-incubation period of 24 and 48 hours. All
      huprines showed protective effects in both undifferentiated and NGF
      differentiated cells, however only in differentiated cells the effect was
      dependent on cholinergic receptors as atropine (muscarinic antagonist, 0.1 uM)
      and mecamylamine (nicotinic antagonist, 100 uM) reverted the neuroprotection
      action of huprines. The decrease in SOD activity observed after oxidative insult
      was overcome in the presence of huprines and this effect was not mediated by
      muscarinic or nicotinic receptors. In conclusion, huprines displayed
      neuroprotective properties as previously observed in in vivo studies. In
      addition, these effects were mediated by cholinergic receptors only in
      differentiated cells. However, a non-cholinergic mechanism, probably through an
      increase in SOD activity, seems to be also involved in the neuroprotective
      effects of huprines. 

PMID- 24086339
TI  - Depressive symptoms and risk of new cardiovascular events or death in patients
      with myocardial infarction: a population-based longitudinal study examining
      health behaviors and health care interventions.
AB  - BACKGROUND: Depressive symptoms is associated with adverse cardiovascular
      outcomes in patients with myocardial infarction (MI), but the underlying
      mechanisms are unclear and it remains unknown whether subgroups of patients are
      at a particularly high relative risk of adverse outcomes. We examined the risk of
      new cardiovascular events and/or death in patients with depressive symptoms
      following first-time MI taking into account other secondary preventive factors.
      We further explored whether we could identify subgroups of patients with a
      particularly high relative risk of adverse outcomes. METHODS AND RESULTS: We
      conducted a prospective population-based cohort study of 897 patients discharged
      with first-time MI between 1 January 2009 and 31 December 2009, and followed up
      until 31 July 2012. Depressive symptoms were found in 18.6% using the Hospital
      Anxiety and Depression Scale (HADS-D>=8). A total of 239 new cardiovascular
      events, 95 deaths, and 288 composite events (239 new cardiovascular events and 49
      deaths) occurred during 1,975 person-years of follow-up. Event-free survival was
      evaluated using Cox regression analysis. Compared to the 730 patients without
      depressive symptoms (HADS-D<8), the 167 patients with depressive symptoms (HADS
      D>=8) had age- and sex-adjusted hazard ratios [HR] (95% confidence interval [CI])
      of 1.53 (95% CI, 1.14-2.05) for a new cardiovascular event, 3.10 (95% CI, 2.04
      4.71) for death and 1.77 (95% CI, 1.36-2.31) for a composite event. The
      associations were attenuated when adjusted for disease severity, comorbid
      conditions and physical inactivity; HR = 1.17 (95% CI, 0.85-1.61) for a new
      cardiovascular event, HR = 2.01 (95% CI, 1.28-3.16) for death, and HR = 1.33 (95%
      CI, 1.00-1.76) for a composite event. No subgroups of patients had a particularly
      high risk of adverse outcomes. CONCLUSIONS: Depressive symptoms following first
      time MI was an independent prognostic risk factor for death, but not for new
      cardiovascular events. We found no subgroups of patients with a particularly high
      relative risk of adverse outcomes.

PMID- 24086340
TI  - Association of p62/SQSTM1 excess and oral carcinogenesis.
AB  - p62/SQSTM1 (sequestosome1) has never been evaluated in oral epithelium. In order
      to clarify the role of p62/SQSTM1 in carcinogenesis in oral epithelium, both
      p62/SQSTM1 and Nrf2 were immunohistochemically evaluated in 54 carcinomas and 14
      low grade dysplasias. p62/SQSTM1 knockdowns were also designed in oral cancer
      cells, and we analyzed the Nrf2 pathway, GSH contents and ROS accumulation. The
      association between p62/SQSTM1 excess and prognosis was addressed in a clinical
      cohort of oral carcinoma cases. p62/SQSTM1 excess was more obvious in carcinomas,
      but Nrf2 was abundant in almost all samples of the oral epithelium. In oral
      carcinoma cells, p62/SQSTM1 knockdown did not affect the Nrf2-Keap1 pathway but
      did significantly reduce GSH content with subsequent ROS accumulation, and caused
      cell growth inhibition in the irradiated condition. Finally, p62/SQSTM1 excess
      was associated with poor prognosis in a clinical cohort. In oral epithelial
      carcinogenesis, p62/SQSTM1 excess played a role in GSH induction rather than Nrf2
      accumulation, and may cause resistance to cytotoxic stresses such as radiation or
      chemotherapy. Immunohistochemical evaluation of p62/SQSTM1 may be a potential
      significant marker to identify early carcinogenesis, chemo-radiotherapeutic
      resistance or poor prognosis of oral squamous cell carcinomas. 

PMID- 24086342
TI  - Taxonomic distinctness and richness of helminth parasite assemblages of
      freshwater fishes in Mexican hydrological basins.
AB  - In this paper, we analyse the distributional patterns of adult helminth parasites
      of freshwater fishes with respect to the main hydrological basins of Mexico. We
      use the taxonomic distinctness and the variation in taxonomic distinctness to
      explore patterns of parasite diversity and how these patterns change between
      zoogeographical regions. We address questions about the factors that determine
      the variation of observed diversity of helminths between basins. We also
      investigate patterns of richness, taxonomic distinctness and distance decay of
      similarity amongst basins. Our analyses suggest that the evolution of the fauna
      of helminth parasites in Mexico is mostly dominated by independent host
      colonization events and that intra--host speciation could be a minor factor
      explaining the origin of this diversity. This paper points out a clear separation
      between the helminth faunas of northern--nearctic and southern--neotropical
      components in Mexican continental waters, suggesting the availability of two
      distinct taxonomic pools of parasites in Mexican drainage basins. Data identifies
      Mexican drainage basins as unities inhabited by freshwater fishes, hosting a
      mixture of neotropical and nearctic species, in addition, data confirms
      neotropical and neartic basins/helminth faunas. The neotropical basins of Mexico
      are host to a richest and more diversified helminth fauna, including more
      families, genera and species, compared to the less rich and less diverse helminth
      fauna in the nearctic basins. The present analysis confirms distance--decay as
      one of the important factors contributing to the patterns of diversity observed.
      The hypothesis that helminth diversity could be explained by the ichthyological
      diversity of the basin received no support from present analysis.

PMID- 24086343
TI  - A conserved virulence plasmidic region contributes to the virulence of the
      multiresistant Escherichia coli meningitis strain S286 belonging to phylogenetic
      group C.
AB  - Recent isolation of the non-K1 Escherichia coli neonatal meningitis strain S286,
      belonging to phylogroup C, which is closely related to major group B1, and
      producing an extended-spectrum beta-lactamase, encouraged us to seek the genetic
      determinants responsible for its virulence. We show that S286 belongs to the
      sequence O type ST23O78 and harbors 4 large plasmids. The largest one, pS286colV
      (~120 kb), not related to resistance, contains genes characteristic of a
      Conserved Virulence Plasmidic (CVP) region initially identified in B2 extra
      intestinal avian pathogenic E. coli (APEC) strains and in the B2 neonatal
      meningitis E. coli strain S88. The sequence of this CVP region has a strong
      homology (98%) with that of the recently sequenced plasmid pChi7122-1 of the O78
      APEC strain Chi7122. A CVP plasmid-cured variant of S286 was less virulent than
      the wild type strain in a neonatal rat sepsis model with a significant lower
      level of bacteremia at 24 h (4.1 +/- 1.41 versus 2.60 +/- 0.16 log CFU/ml, p =
      0.001) and mortality. However, the mortality in the model of adult mice was
      comparable between wild type and variant indicating that pS286colV is not
      sufficient by itself to fully explain the virulence of S286. Gene expression
      analysis of pS286colV in iron depleted environment was very close to that of
      pS88, suggesting that genes of CVP region may be expressed similarly in two very
      different genetic backgrounds (group C versus group B2). Screening a collection
      of 178 human A/B1 extraintestinal pathogenic E. coli (ExPEC) strains revealed
      that the CVP region is highly prevalent (23%) and MLST analysis indicated that
      these CVP positive strains belong to several clusters and mostly to phylogroup C.
      The virulence of S286 is explained in part by the presence of CVP region and this
      region has spread in different clusters of human A/B1 ExPEC, especially in group
      C.

PMID- 24086341
TI  - Drug-induced reactivation of apoptosis abrogates HIV-1 infection.
AB  - HIV-1 blocks apoptosis, programmed cell death, an innate defense of cells against
      viral invasion. However, apoptosis can be selectively reactivated in HIV-infected
      cells by chemical agents that interfere with HIV-1 gene expression. We studied
      two globally used medicines, the topical antifungal ciclopirox and the iron
      chelator deferiprone, for their effect on apoptosis in HIV-infected H9 cells and
      in peripheral blood mononuclear cells infected with clinical HIV-1 isolates. Both
      medicines activated apoptosis preferentially in HIV-infected cells, suggesting
      that the drugs mediate escape from the viral suppression of defensive apoptosis.
      In infected H9 cells, ciclopirox and deferiprone enhanced mitochondrial membrane
      depolarization, initiating the intrinsic pathway of apoptosis to execution, as
      evidenced by caspase-3 activation, poly(ADP-ribose) polymerase proteolysis, DNA
      degradation, and apoptotic cell morphology. In isolate-infected peripheral blood
      mononuclear cells, ciclopirox collapsed HIV-1 production to the limit of viral
      protein and RNA detection. Despite prolonged monotherapy, ciclopirox did not
      elicit breakthrough. No viral re-emergence was observed even 12 weeks after drug
      cessation, suggesting elimination of the proviral reservoir. Tests in mice
      predictive for cytotoxicity to human epithelia did not detect tissue damage or
      activation of apoptosis at a ciclopirox concentration that exceeded by orders of
      magnitude the concentration causing death of infected cells. We infer that
      ciclopirox and deferiprone act via therapeutic reclamation of apoptotic
      proficiency (TRAP) in HIV-infected cells and trigger their preferential
      elimination. Perturbations in viral protein expression suggest that the
      antiretroviral activity of both drugs stems from their ability to inhibit
      hydroxylation of cellular proteins essential for apoptosis and for viral
      infection, exemplified by eIF5A. Our findings identify ciclopirox and deferiprone
      as prototypes of selectively cytocidal antivirals that eliminate viral infection
      by destroying infected cells. A drug-based drug discovery program, based on these
      compounds, is warranted to determine the potential of such agents in clinical
      trials of HIV-infected patients. 

PMID- 24086345
TI  - Next-generation sequence analysis of cancer xenograft models.
AB  - Next-generation sequencing (NGS) studies in cancer are limited by the amount,
      quality and purity of tissue samples. In this situation, primary xenografts have
      proven useful preclinical models. However, the presence of mouse-derived stromal
      cells represents a technical challenge to their use in NGS studies. We examined
      this problem in an established primary xenograft model of small cell lung cancer
      (SCLC), a malignancy often diagnosed from small biopsy or needle aspirate
      samples. Using an in silico strategy that assign reads according to species-of
      origin, we prospectively compared NGS data from primary xenograft models with
      matched cell lines and with published datasets. We show here that low-coverage
      whole-genome analysis demonstrated remarkable concordance between published
      genome data and internal controls, despite the presence of mouse genomic DNA.
      Exome capture sequencing revealed that this enrichment procedure was highly
      species-specific, with less than 4% of reads aligning to the mouse genome. Human
      specific expression profiling with RNA-Seq replicated array-based gene expression
      experiments, whereas mouse-specific transcript profiles correlated with published
      datasets from human cancer stroma. We conclude that primary xenografts represent
      a useful platform for complex NGS analysis in cancer research for tumours with
      limited sample resources, or those with prominent stromal cell populations. 

PMID- 24086344
TI  - Gene expression profiling of a hypoxic seizure model of epilepsy suggests a role
      for mTOR and Wnt signaling in epileptogenesis.
AB  - Microarray profiling was used to investigate gene expression in the hypoxic
      seizure model of acquired epilepsy in the rat, with the aim of characterizing
      functional pathways which are persistently activated or repressed during
      epileptogenesis. Hippocampal and cortical tissues were transcriptionally profiled
      over a one week period following an initial series of seizures induced by mild
      hypoxia at post-natal day 10 (P10), and the gene expression data was then
      analyzed with a focus on gene set enrichment analysis, an approach which
      emphasizes regulation of entire pathways rather than of individual genes. Animals
      were subjected to one of three conditions: a control with no hypoxia, hypoxic
      seizures, and hypoxic seizures followed by treatment with the AMPAR antagonist
      NBQX, a compound currently proposed to be a modulator of epileptogenesis. While
      temporal gene expression in the control samples was found to be consistent with
      known processes of neuronal maturation in the rat for the given time window, the
      hypoxic seizure response was found to be enriched for components of the PI3K/mTOR
      and Wnt signaling pathways, alongside gene sets representative of glutamatergic,
      synaptic and axonal processes, perhaps regulated as a downstream consequence of
      activation of these pathways. Wnt signaling components were also found enriched
      in the more specifically epileptogenic NBQX-responsive gene set. While activation
      of the mTOR pathway is consistent with its known role in epileptogenesis and
      strengthens the case for mTOR or PI3K pathway inhibitors as potential anti
      epileptogenic drugs, investigation of the role of Wnt signaling and the effect of
      appropriate inhibitors might offer a parallel avenue of research toward anti
      epileptogenic treatment of epilepsy. 

PMID- 24086346
TI  - Early human prostate adenocarcinomas harbor androgen-independent cancer cells.
AB  - Although blockade of androgen receptor (AR) signaling represents the main
      treatment for advanced prostate cancer (PrCa), many patients progress to a lethal
      phenotype of "Castration-Resistant" prostate cancer (CR-PrCa). With the
      hypothesis that early PrCa may harbor a population of androgen-unresponsive
      cancer cells as precursors to CR-recurrent disease, we undertook the propagation
      of androgen-independent cells from PrCa-prostatectomy samples of early, localized
      (Stage-I) cases. A collection of 120 surgical specimens from prostatectomy cases
      was established, among which 54 were adenocarcinomas. Hormone-free cell culture
      conditions were developed allowing routine propagation of cells expressing
      prostate basal cell markers and stem/progenitor cell markers, and which
      proliferated as spheres/spheroids in suspension cultures. Colonies of androgen
      independent epithelial cells grew out from 30/43 (70%) of the adenocarcinoma
      cases studied in detail. Fluorescence microscopy and flow cytometry showed that
      CR-PrCa cells were positive for CD44, CD133, CK5/14, c-kit, integrin alpha2beta1,
      SSEA4, E-Cadherin and Aldehyde Dehydrogenase (ALDH). All 30 CR-PrCa cell cultures
      were also TERT-positive, but negative for TMPRSS2-ERG. Additionally, a subset of
      22 of these CR-PrCa cell cultures was examined by orthotopic xenografting in
      intact and castrated SCID mice, generating histologically typical locally
      invasive human PrCa or undifferentiated cancers, respectively, in 6-8 weeks.
      Cultured PrCa cells and orthotopically-induced in vivo cancers lacked PSA
      expression. We report here the propagation of Cancer Initiating Cells (CIC)
      directly from Stage I human PrCa tissue without selection or genetic
      manipulation. The propagation of stem/progenitor-like CR-PrCa cells derived from
      early human prostate carcinomas suggests the existence of a subpopulation of
      cells resistant to androgen-deprivation therapy and which may drive the
      subsequent emergence of disseminated CR-PrCa. 

PMID- 24086347
TI  - HLA class I and class II conserved extended haplotypes and their fragments or
      blocks in Mexicans: implications for the study of genetic diversity in admixed
      populations.
AB  - Major histocompatibility complex (MHC) genes are highly polymorphic and
      informative in disease association, transplantation, and population genetics
      studies with particular importance in the understanding of human population
      diversity and evolution. The aim of this study was to describe the HLA diversity
      in Mexican admixed individuals. We studied the polymorphism of MHC class I (HLA
      A, -B, -C), and class II (HLA-DRB1, -DQB1) genes using high-resolution sequence
      based typing (SBT) method and we structured the blocks and conserved extended
      haplotypes (CEHs) in 234 non-related admixed Mexican individuals (468 haplotypes)
      by a maximum likelihood method. We found that HLA blocks and CEHs are primarily
      from Amerindian and Caucasian origin, with smaller participation of African and
      recent Asian ancestry, demonstrating a great diversity of HLA blocks and CEHs in
      Mexicans from the central area of Mexico. We also analyzed the degree of
      admixture in this group using short tandem repeats (STRs) and HLA-B that
      correlated with the frequency of most probable ancestral HLA-C/-B and -DRB1/-DQB1
      blocks and CEHs. Our results contribute to the analysis of the diversity and
      ancestral contribution of HLA class I and HLA class II alleles and haplotypes of
      Mexican admixed individuals from Mexico City. This work will help as a reference
      to improve future studies in Mexicans regarding allotransplantation, immune
      responses and disease associations. 

PMID- 24086348
TI  - Environmental feedbacks and engineered nanoparticles: mitigation of silver
      nanoparticle toxicity to Chlamydomonas reinhardtii by algal-produced organic
      compounds.
AB  - The vast majority of nanotoxicity studies measures the effect of exposure to a
      toxicant on an organism and ignores the potentially important effects of the
      organism on the toxicant. We investigated the effect of citrate-coated silver
      nanoparticles (AgNPs) on populations of the freshwater alga Chlamydomonas
      reinhardtii at different phases of batch culture growth and show that the AgNPs
      are most toxic to cultures in the early phases of growth. We offer strong
      evidence that reduced toxicity occurs because extracellular dissolved organic
      carbon (DOC) compounds produced by the algal cells themselves mitigate the
      toxicity of AgNPs. We analyzed this feedback with a dynamic model incorporating
      algal growth, nanoparticle dissolution, bioaccumulation of silver, DOC production
      and DOC-mediated inactivation of nanoparticles and ionic silver. Our findings
      demonstrate how the feedback between aquatic organisms and their environment may
      impact the toxicity and ecological effects of engineered nanoparticles. 

PMID- 24086349
TI  - A neglected issue on sexual well-being following breast cancer diagnosis and
      treatment among Chinese women.
AB  - BACKGROUND: Changes to sexual well-being can be one of the most problematic
      quality of life issues following the diagnosis and treatment of breast cancer.
      The objectives of the present study were to evaluate changes to sexual well-being
      following breast cancer, to expand upon the existing body of knowledge pertaining
      to breast cancer and sexuality, and to provide the necessary information for
      implementing future interventions that may help improve the quality of life in
      breast cancer patients. METHODS: This study was mixed with qualitative and
      quantitative designs. Twenty patients with breast cancer were recruited for in
      depth interviews. The central questions covered a patient's cancer experience and
      perceptions of sexual activities following breast cancer. According to the
      findings of the qualitative study, we performed a quantitative study using a
      structured questionnaire to collect data on patient's experience and attitude to
      sexual well-being following breast cancer diagnosis and treatment. RESULTS: Based
      on the qualitative analysis, seven main themes emerged: (1) Decrease in sexual
      frequency; (2) Lack of sexual interest; (3) Menopausal symptoms; (4) Body image
      changes; (5) Effects on marital relationship; (6) Misconceptions about sex; (7)
      The need for professional consultation. Results from the quantitative study
      further supported the findings from the qualitative analysis, where changes to
      sexual well-being were common following cancer diagnosis and treatment and it was
      a neglected issue among Chinese women. CONCLUSIONS: The present study highlights
      the significant changes to sexual well-being following breast cancer, in addition
      to the lack of knowledge and misconceptions of sexual activity among patients.
      Addressing these problems will help improve a patient's quality of life. The
      findings of this study could help healthcare professionals recognize the sexual
      issues faced by women with breast cancer and ultimately promote a healthy life.

PMID- 24086350
TI  - Mortality following hip fracture in men with prostate cancer.
AB  - BACKGROUND: Hip fractures are associated with increased mortality and are a known
      adverse effect of androgen deprivation therapy (ADT) for prostate cancer (PCa).
      It was our aim to evaluate how mortality after hip fracture is modified by PCa
      and ADT. METHODS: PCa dataBase Sweden (PCBaSe 2.0) is based on the National PCa
      Register and also contains age and county-matched PCa-free men. We selected all
      men (n = 14,205) who had been hospitalized with a hip fracture between 2006 and
      2010; 2,300 men had a prior PCa diagnosis of whom 1,518 (66%) were on ADT prior
      to date of fracture. Risk of death was estimated with cumulative incidence and
      standardized mortality ratios (SMRs) to make comparisons with the entire PCa
      population and the general population. RESULTS: Cumulative incidences indicated
      that there was a higher risk of death following a hip fracture for PCa men on ADT
      than for PCa men not on ADT or PCa-free men, particularly in the first year. The
      SMRs showed that PCa men on ADT with a hip fracture were 2.44 times more likely
      to die than the comparison cohort of all PCa men (95%CI: 2.29-2.60). This risk
      was especially increased during the first month (5.64 (95%CI: 4.16-7.48)). In
      absolute terms, hip fractures were associated with 20 additional deaths per 1,000
      person-years in PCa men not on ADT, but 30 additional deaths per 1,000 person
      years for PCa men on ADT, compared to all PCa men. CONCLUSION: Hip fractures are
      associated with higher all-cause mortality in PCa men on ADT than in PCa men not
      on ADT or PCa-free men, especially within the first three months.

PMID- 24086351
TI  - Field-isolated genotypes of Mycobacterium bovis vary in virulence and influence
      case pathology but do not affect outbreak size.
AB  - Strains of many infectious agents differ in fundamental epidemiological
      parameters including transmissibility, virulence and pathology. We investigated
      whether genotypes of Mycobacterium bovis (the causative agent of bovine
      tuberculosis, bTB) differ significantly in transmissibility and virulence,
      combining data from a nine-year survey of the genetic structure of the M. bovis
      population in Northern Ireland with detailed records of the cattle population
      during the same period. We used the size of herd breakdowns as a proxy measure of
      transmissibility and the proportion of skin test positive animals (reactors) that
      were visibly lesioned as a measure of virulence. Average breakdown size increased
      with herd size and varied depending on the manner of detection (routine herd
      testing or tracing of infectious contacts) but we found no significant variation
      among M. bovis genotypes in breakdown size once these factors had been accounted
      for. However breakdowns due to some genotypes had a greater proportion of
      lesioned reactors than others, indicating that there may be variation in
      virulence among genotypes. These findings indicate that the current bTB control
      programme may be detecting infected herds sufficiently quickly so that
      differences in virulence are not manifested in terms of outbreak sizes. We also
      investigated whether pathology of infected cattle varied according to M. bovis
      genotype, analysing the distribution of lesions recorded at post mortem
      inspection. We concentrated on the proportion of cases lesioned in the lower
      respiratory tract, which can indicate the relative importance of the respiratory
      and alimentary routes of infection. The distribution of lesions varied among
      genotypes and with cattle age and there were also subtle differences among
      breeds. Age and breed differences may be related to differences in susceptibility
      and husbandry, but reasons for variation in lesion distribution among genotypes
      require further investigation. 

PMID- 24086352
TI  - Homeopathy for depression: a randomized, partially double-blind, placebo
      controlled, four-armed study (DEP-HOM).
AB  - BACKGROUND: The specific clinical benefit of the homeopathic consultation and of
      homeopathic remedies in patients with depression has not yet been investigated.
      AIMS: To investigate the 1) specific effect of individualized homeopathic Q
      potencies compared to placebo and 2) the effect of an extensive homeopathic case
      taking (case history I) compared to a shorter, rather conventional one (case
      history II) in the treatment of acute major depression (moderate episode) after
      six weeks. METHODS: A randomized, partially double-blind, placebo-controlled,
      four-armed trial using a 2*2 factorial design with a six-week study duration per
      patient was performed. RESULTS: A total of 44 from 228 planned patients were
      randomized (2?1?2?1 randomization: 16 homeopathic Q-potencies/case history I, 7
      placebo/case history I, 14 homeopathic Q-potencies/case history II, 7
      placebo/case history II). Because of recruitment problems, the study was
      terminated prior to full recruitment, and was underpowered for the preplanned
      confirmatory hypothesis testing. Exploratory data analyses showed heterogeneous
      and inconclusive results with large variance in the sample. The mean difference
      for the Hamilton-D after 6 weeks was 2.0 (95%CI -1.2;5.2) for Q-potencies vs.
      placebo and -3.1 (-5.9;-0.2) for case history I vs. case history II. Overall, no
      consistent or clinically relevant results across all outcomes between homeopathic
      Q-potencies versus placebo and homeopathic versus conventional case taking were
      observed. The frequency of adverse events was comparable for all groups.
      CONCLUSIONS: Although our results are inconclusive, given that recruitment into
      this trial was very difficult and we had to terminate early, we cannot recommend
      undertaking a further trial addressing this question in a similar setting. Prof.
      Dr. Claudia Witt had full access to all the data in the study and takes
      responsibility for the integrity of the data and the accuracy of the data
      analysis. TRIAL REGISTRATION: clinicaltrials.gov identifier NCT01178255. Protocol
      publication: http://www.trialsjournal.com/content/12/1/43.

PMID- 24086353
TI  - FASL rs763110 polymorphism contributes to cancer risk: an updated meta-analysis
      involving 43,295 subjects.
AB  - BACKGROUND: Published studies investigating the association between genetic
      polymorphism -884C/T (rs763110) of the FAS ligand (FASL) promoter and cancer risk
      reported inconclusive results. To derive a more precise estimation of the
      relationship, we performed an updated meta-analysis of all eligible studies.
      METHODOLOGY/PRINCIPAL FINDINGS: We carried out a meta-analysis, including 47
      studies with 19,810 cases and 23,485 controls, to confirm a more conclusive
      association between the FASL rs763110 polymorphism and cancer susceptibility.
      Overall, significantly reduced cancer risk was associated with the variant -884T
      when all studies were pooled (TC vs. CC: OR = 0.83, 95%CI = 0.75-0.92;
      P(heterogeneity)<0.001; TT+TC vs. CC: OR = 0.85, 95%CI = 0.77-0.94;
      P(heterogeneity)<0.001). Stratified analysis revealed that there was a
      statistically reduced cancer risk in Asians (TC vs. CC: OR = 0.76, 95%CI = 0.67
      0.87; P(heterogeneity)<0.001; TT+TC vs. CC: OR = 0.79, 95%CI = 0.70-0.90;
      P(heterogeneity)<0.001) and in patients with cancers of head and neck (TC vs. CC:
      OR = 0.87, 95%CI = 0.77-0.99; P(heterogeneity) = 0.118; TT+TC vs. CC: OR = 0.88,
      95%CI = 0.78-0.99; P(heterogeneity) = 0.168) and ovarian cancer (TC vs. CC: OR =
      0.67, 95%CI = 0.49-0.90; P(heterogeneity) = 0.187; TT+TC vs. CC: OR = 0.64, 95%CI
      = 0.48-0.86; P(heterogeneity) = 0.199). Meta-regression showed that ethnicity (p
      = 0.029) and genotyping method (p = 0.043) but not cancer types (p = 0.772),
      sample size (p = 0.518), or source of controls (p = 0.826) were the source of
      heterogeneity in heterozygote comparison. CONCLUSION: Our results suggest that
      the FASL polymorphism rs763110 is associated with a significantly reduced risk of
      cancer, especially in Asian populations.

PMID- 24086354
TI  - Asymmetric migration of human keratinocytes under mechanical stretch and
      cocultured fibroblasts in a wound repair model.
AB  - Keratinocyte migration during re-epithelization is crucial in wound healing under
      biochemical and biomechanical microenvironment. However, little is known about
      the underlying mechanisms whereby mechanical tension and cocultured fibroblasts
      or keratinocytes modulate the migration of keratinocytes or fibroblasts. Here we
      applied a tensile device together with a modified transwell assay to determine
      the lateral and transmembrane migration dynamics of human HaCaT keratinocytes or
      HF fibroblasts. A novel pattern of asymmetric migration was observed for
      keratinocytes when they were cocultured with non-contact fibroblasts, i.e., the
      accumulative distance of HaCaT cells was significantly higher when moving away
      from HF cells or migrating from down to up cross the membrane than that when
      moving close to HF cells or when migrating from up to down, whereas HF migration
      was symmetric. This asymmetric migration was mainly regulated by EGF derived from
      fibroblasts, but not transforming growth factor alpha or beta1 production.
      Mechanical stretch subjected to fibroblasts fostered keratinocyte asymmetric
      migration by increasing EGF secretion, while no role of mechanical stretch was
      found for EGF secretion by keratinocytes. These results provided a new insight
      into understanding the regulating mechanisms of two- or three-dimensional
      migration of keratinocytes or fibroblasts along or across dermis and epidermis
      under biomechanical microenvironment. 

PMID- 24086356
TI  - Feeding on multiple sources: towards a universal parameterization of the
      functional response of a generalist predator allowing for switching.
AB  - Understanding of complex trophic interactions in ecosystems requires correct
      descriptions of the rate at which predators consume a variety of different prey
      species. Field and laboratory data on multispecies communities are rarely
      sufficient and usually cannot provide an unambiguous test for the theory. As a
      result, the conventional way of constructing a multi-prey functional response is
      speculative, and often based on assumptions that are difficult to verify.
      Predator responses allowing for prey selectivity and active switching are thought
      to be more biologically relevant compared to the standard proportion-based
      consumption. However, here we argue that the functional responses with switching
      may not be applicable to communities with a broad spectrum of resource types. We
      formulate a set of general rules that a biologically sound parameterization of a
      predator functional response should satisfy, and show that all existing
      formulations for the multispecies response with prey selectivity and switching
      fail to do so. Finally, we propose a universal framework for parameterization of
      a multi-prey functional response by combining patterns of food selectivity and
      proportion-based feeding. 

PMID- 24086355
TI  - Modeling the conformational changes underlying channel opening in CFTR.
AB  - Mutations in the gene encoding the cystic fibrosis transmembrane conductance
      regulator protein (CFTR) cause cystic fibrosis (CF), the most common life
      shortening genetic disease among Caucasians. Although general features of the
      structure of CFTR have been predicted from homology models, the conformational
      changes that result in channel opening and closing have yet to be resolved. We
      created new closed- and open-state homology models of CFTR, and performed
      targeted molecular dynamics simulations of the conformational transitions in a
      channel opening event. The simulations predict a conformational wave that starts
      at the nucleotide binding domains and ends with the formation of an open
      conduction pathway. Changes in side-chain interactions are observed in all major
      domains of the protein, and experimental confirmation was obtained for a novel
      intra-protein salt bridge that breaks near the end of the transition. The models
      and simulation add to our understanding of the mechanism of ATP-dependent gating
      in this disease-relevant ion channel. 

PMID- 24086357
TI  - A recombinant Anticarsia gemmatalis MNPV harboring chiA and v-cath genes from
      Choristoneura fumiferana defective NPV induce host liquefaction and increased
      insecticidal activity.
AB  - One of the interesting features of Anticarsia gemmatalis multiple
      nucleopolyhedrovirus isolate 2D (AgMNPV-2D) genome is the absence of chitinase
      (chiA) and cathepsin (v-cath) genes. This characteristic may be responsible for
      the lack of liquefaction and melanization in A. gemmatalis larvae killed by
      AgMNPV-2D infection. This study aimed to test the hypothesis that CHIA and V-CATH
      proteins from Choristonera fumiferana DEF multiple nucleopolyhedrovirus
      (CfDEFNPV) are able to liquefy and melanize the cuticle of A. gemmatalis larvae
      infected by a recombinant AgMNPV containing chiA and v-cath genes inserted in its
      genome. A fragment from the CfDefNPV genome containing chiA and v-cath genes was
      inserted into the genome of AgMNPV-2D. The recombinant virus (vAgp2100Cf.chiA/v
      cath) was purified and used to infect insect cells and larvae. Transcripts of v
      cath and chiA genes were detected along the infection of insect cells by qRT-PCR,
      from early to late phases of infection. The analysis of A. gemmatalis larvae
      killed by vAgp2100Cf.chiA/v-cath infection confirmed the hypothesis proposed. The
      vAgp2100Cf.chiA/v-cath showed higher insecticidal activity against third instar
      A. gemmatalis larvae when compared to AgMNPV-2D. The mean time to death was also
      lower for the vAgp2100Cf.chiA/v-cath when compared to AgMNPV-2D at 10 days post
      infection. Occlusion body production was higher in A. gemmatalis larvae infected
      with vAgp2100Cf.chiA/v-cath when compared to AgMNPV-2D. Enzyme assays showed
      higher chitinase and cysteine protease activities in insect cells and insects
      infected with vAgp2100Cf.chiA/v-cath when compared to AgMNPV-2D. The introduction
      of chiA and v-cath genes into the genome of AgMNPV improves its insecticidal
      activity against A. gemmatalis larvae and this recombinant virus could be used as
      an alternative to the wild type virus to control this important insect pest. 

PMID- 24086358
TI  - Altered olfactory processing of stress-related body odors and artificial odors in
      patients with panic disorder.
AB  - BACKGROUND: Patients with Panic Disorder (PD) direct their attention towards
      potential threat, followed by panic attacks, and increased sweat production. Ones
      own anxiety sweat odor influences the attentional focus, and discrimination of
      threat or non-threat. Since olfactory projection areas overlap with neuronal
      areas of a panic-specific fear network, the present study investigated the
      neuronal processing of odors in general and of stress-related sweat odors in
      particular in patients with PD. METHODS: A sample of 13 patients with PD with/
      without agoraphobia and 13 age- and gender-matched healthy controls underwent an
      fMRI investigation during olfactory stimulation with their stress-related sweat
      odors (TSST, ergometry) as well as artificial odors (peach, artificial sweat) as
      non-fearful non-body odors. PRINCIPAL FINDINGS: The two groups did not differ
      with respect to their olfactory identification ability. Independent of the kind
      of odor, the patients with PD showed activations in fronto-cortical areas in
      contrast to the healthy controls who showed activations in olfaction-related
      areas such as the amygdalae and the hippocampus. For artificial odors, the
      patients with PD showed a decreased neuronal activation of the thalamus, the
      posterior cingulate cortex and the anterior cingulate cortex. Under the
      presentation of sweat odor caused by ergometric exercise, the patients with PD
      showed an increased activation in the superior temporal gyrus, the supramarginal
      gyrus, and the cingulate cortex which was positively correlated with the severity
      of the psychopathology. For the sweat odor from the anxiety condition, the
      patients with PD showed an increased activation in the gyrus frontalis inferior,
      which was positively correlated with the severity of the psychopathology.
      CONCLUSIONS: The results suggest altered neuronal processing of olfactory stimuli
      in PD. Both artificial odors and stress-related body odors activate specific
      parts of a fear-network which is associated with an increased severity of the
      psychopathology.

PMID- 24086359
TI  - Proteomic investigation of aphid honeydew reveals an unexpected diversity of
      proteins.
AB  - Aphids feed on the phloem sap of plants, and are the most common honeydew
      producing insects. While aphid honeydew is primarily considered to comprise
      sugars and amino acids, its protein diversity has yet to be documented. Here, we
      report on the investigation of the honeydew proteome from the pea aphid
      Acyrthosiphon pisum. Using a two-Dimensional Differential in-Gel Electrophoresis
      (2D-Dige) approach, more than 140 spots were isolated, demonstrating that aphid
      honeydew also represents a diverse source of proteins. About 66% of the isolated
      spots were identified through mass spectrometry analysis, revealing that the
      protein diversity of aphid honeydew originates from several organisms (i.e. the
      host aphid and its microbiota, including endosymbiotic bacteria and gut flora).
      Interestingly, our experiments also allowed to identify some proteins like
      chaperonin, GroEL and Dnak chaperones, elongation factor Tu (EF-Tu), and
      flagellin that might act as mediators in the plant-aphid interaction. In addition
      to providing the first aphid honeydew proteome analysis, we propose to reconsider
      the importance of this substance, mainly acknowledged to be a waste product, from
      the aphid ecology perspective. 

PMID- 24086360
TI  - Nitric oxide signaling exerts bidirectional effects on plasticity inductions in
      amygdala.
AB  - It has been well known that long-term potentiation (LTP) of synaptic transmission
      in the lateral nucleus of the amygdala (LA) constitutes an essential cellular
      mechanism contributing to encoding of conditioned fear. Nitric oxide (NO),
      produced by activation of the postsynaptic N-methyl-D-aspartate receptors (NMDAR)
      in thalamic input to the LA, has been thought to promote LTP, contributing to the
      establishment of conditioned fear. However, it is not known whether and how NO,
      released from cortical input to the LA, plays the role on the plasticity
      induction and fear memory. Here we report that the diffusion of NO, released in
      response to activation of presynaptic NMDAR on cortical afferent fibers in the
      LA, could suppress heterosynaptically a form of presynaptic kainate receptor
      (KAR) dependent LTP (pre-LTP) in thalamic input, which was induced by low
      frequency presynaptic stimuli without postsynaptic depolarization. We also
      confirmed that NO, produced by activation of postsynaptic NMDAR in thalamic
      input, can promote postsynaptic NMDAR-dependent LTP (post-LTP), which was induced
      by pairing protocol. These LTPs were occluded following fear conditioning,
      indicating that they could contribute to encoding of conditioned fear memory.
      However, their time courses are different; Post-LTP was more rapidly formed than
      pre-LTP in the course of fear conditioning. NO, produced by activation of
      presynaptic NMDAR in cortical input and postsynaptic NMDAR in thalamic input, may
      control conditioned fear by suppressing pre-LTP and promoting post-LTP,
      respectively, in thalamic input to the LA. 

PMID- 24086361
TI  - Kinetic characterization of an intestinal trefoil factor receptor.
AB  - OBJECTIVE: To determine whether intestinal epithelial cells have a receptor for
      intestinal trefoil factor and characterize receptor-ligand binding kinetics.
      METHODS: Radioligand binding assays were performed to characterize the binding
      kinetics between [(125)I]-labeled ITF and IEC-6, HT-29, Caco2 and HaCaT cells.
      The K d, Bmax and other kinetic variables describing the interaction between ITF
      and its potential receptors were determined. RESULTS: Radioligand binding assays
      performed at 4  degrees C showed that the K d value for the association between
      [(125)I]-ITF and IEC-6, HT-29, and Caco2 cells were 1.99 +/- 0.12 * 10(-9) M,
      3.89 +/- 0.42 * 10(-9) M, and 2.04 +/- 0.17 * 10(-9) M, respectively. Bmax values
      were 1.17 +/- 0.04 * 10(11), 3.97 +/- 0.29 * 10(11), and 2.03 +/- 0.08 * 10(11)
      sites/cell, respectively. The K i values for the interaction between IEC-6, HT
      29, and Caco2 cells and non-labeled ITF were 20.98 +/- 0.57 nM, 36.87 +/- 3.35
      nM, and 21.38 +/- 0.93 nM, respectively, and the IC50 values were 25.21 +/- 0.39
      nM, 40.68 +/- 0.27 nM, and 23.61 +/- 0.25 nM, respectively. Radioligand binding
      kinetic results showed the association rate constants (k +1) for IEC-6, HT-29,
      and Caco2 cells were 0.22 +/- 0.04 min(-1), 0.29 +/- 0.04 min(-1), and 0.26 +/-
      0.05 min(-1), respectively, and the dissociation rate constants (k -1) were 0.06
      +/- 0.02 min(-1), 0.03 +/- 0.01 min(-1), and 0.04 +/- 0.01 min(-1), respectively.
      For the HaCaT cells, the K d was 4.86 +/- 0.28 * 10(-8) M and B max was 5.81 +/-
      0.15 * 10(8) sites/cell, the very low specific binding between [(125)I]-ITF and
      these cells made it impossible to calculate binding kinetic parameters.
      CONCLUSIONS: An ITF-specific receptor appears to be present on the three types of
      intestinal epithelial cells (IEC-6, HT-29, and Caco-2), and there may be no ITF
      receptor on epidermal cells.

PMID- 24086362
TI  - Reduced mitochondrial DNA content associates with poor prognosis of prostate
      cancer in African American men.
AB  - Reduction or depletion of mitochondrial DNA (mtDNA) has been associated with
      cancer progression. Although imbalanced mtDNA content is known to occur in
      prostate cancer, differences in mtDNA content between African American (AA) and
      Caucasian American (CA) men are not defined. We provide the first evidence that
      tumors in AA men possess reduced level of mtDNA compared to CA men. The median
      tumor mtDNA content was reduced in AA men. mtDNA content was also reduced in
      normal prostate tissues of AA men compared to CA men, suggesting a possible
      predisposition to cancer in AA men. mtDNA content was also reduced in benign
      prostatic hyperplasia (BPH) tissue from AA men. Tumor and BPH tissues from
      patients >= 60 years of age possess reduced mtDNA content compared to patients
      <60 years of age. In addition, mtDNA content was higher in normal tissues from
      patients with malignant T3 stage disease compared to patients with T2 stage
      disease. mtDNA levels in matched normal prostate tissues were nearly doubled in
      Gleason grade of >7 compared to <= 7, whereas reduced mtDNA content was observed
      in tumors of Gleason grade >7 compared to <= 7. Together, our data suggest that
      AA men possess lower mtDNA levels in normal and tumor tissues compared to CA men,
      which could contribute to higher risk and more aggressive prostate cancer in AA
      men.

PMID- 24086363
TI  - Direct deposition of gas phase generated aerosol gold nanoparticles into
      biological fluids--corona formation and particle size shifts.
AB  - An ongoing discussion whether traditional toxicological methods are sufficient to
      evaluate the risks associated with nanoparticle inhalation has led to the
      emergence of Air-Liquid interface toxicology. As a step in this process, this
      study explores the evolution of particle characteristics as they move from the
      airborne state into physiological solution. Airborne gold nanoparticles (AuNP)
      are generated using an evaporation-condensation technique. Spherical and
      agglomerate AuNPs are deposited into physiological solutions of increasing
      biological complexity. The AuNP size is characterized in air as mobility diameter
      and in liquid as hydrodynamic diameter. AuNP:Protein aggregation in physiological
      solutions is determined using dynamic light scattering, particle tracking
      analysis, and UV absorption spectroscopy. AuNPs deposited into homocysteine
      buffer form large gold-aggregates. Spherical AuNPs deposited in solutions of
      albumin were trapped at the Air-Liquid interface but was readily suspended in the
      solutions with a size close to that of the airborne particles, indicating that
      AuNP:Protein complex formation is promoted. Deposition into serum and lung fluid
      resulted in larger complexes, reflecting the formation of a more complex protein
      corona. UV absorption spectroscopy indicated no further aggregation of the AuNPs
      after deposition in solution. The corona of the deposited AuNPs shows differences
      compared to AuNPs generated in suspension. Deposition of AuNPs from the aerosol
      phase into biological fluids offers a method to study the protein corona formed,
      upon inhalation and deposition in the lungs in a more realistic way compared to
      particle liquid suspensions. This is important since the protein corona together
      with key particle properties (e.g. size, shape and surface reactivity) to a large
      extent may determine the nanoparticle effects and possible translocation to other
      organs. 

PMID- 24086365
TI  - Emotional processing of personally familiar faces in the vegetative state.
AB  - BACKGROUND: The Vegetative State (VS) is a severe disorder of consciousness in
      which patients are awake but display no signs of awareness. Yet, recent
      functional magnetic resonance imaging (fMRI) studies have demonstrated evidence
      for covert awareness in VS patients by recording specific brain activations
      during a cognitive task. However, the possible existence of incommunicable
      subjective emotional experiences in VS patients remains largely unexplored. This
      study aimed to probe the question of whether VS patients retain a brain ability
      to selectively process external stimuli according to their emotional value and
      look for evidence of covert emotional awareness in patients. METHODS AND
      FINDINGS: In order to explore these questions we employed the emotive impact of
      observing personally familiar faces, known to provoke specific perceptual as well
      as emotional brain activations. Four VS patients and thirteen healthy controls
      first underwent an fMRI scan while viewing pictures of non-familiar faces,
      personally familiar faces and pictures of themselves. In a subsequent imagery
      task participants were asked to actively imagine one of their parent's faces.
      Analyses focused on face and familiarity selective regional brain activations and
      inter-regional functional connectivity. Similar to controls, all patients
      displayed face selective brain responses with further limbic and cortical
      activations elicited by familiar faces. In patients as well as controls,
      Connectivity was observed between emotional, visual and face specific areas,
      suggesting aware emotional perception. This connectivity was strongest in the two
      patients who later recovered. Notably, these two patients also displayed
      selective amygdala activation during familiar face imagery, with one further
      exhibiting face selective activations, indistinguishable from healthy controls.
      CONCLUSIONS: Taken together, these results show that selective emotional
      processing can be elicited in VS patients both by external emotionally salient
      stimuli and by internal cognitive processes, suggesting the ability for covert
      emotional awareness of self and the environment in VS patients.

PMID- 24086364
TI  - Leucine supplementation protects from insulin resistance by regulating adiposity
      levels.
AB  - BACKGROUND: Leucine supplementation might have therapeutic potential in
      preventing diet-induced obesity and improving insulin sensitivity. However, the
      underlying mechanisms are at present unclear. Additionally, it is unclear whether
      leucine supplementation might be equally efficacious once obesity has developed.
      METHODOLOGY/PRINCIPAL FINDINGS: Male C57BL/6J mice were fed chow or a high-fat
      diet (HFD), supplemented or not with leucine for 17 weeks. Another group of HFD
      fed mice (HFD-pairfat group) was food restricted in order to reach an adiposity
      level comparable to that of HFD-Leu mice. Finally, a third group of mice was
      exposed to HFD for 12 weeks before being chronically supplemented with leucine.
      Leucine supplementation in HFD-fed mice decreased body weight and fat mass by
      increasing energy expenditure, fatty acid oxidation and locomotor activity in
      vivo. The decreased adiposity in HFD-Leu mice was associated with increased
      expression of uncoupling protein 3 (UCP-3) in the brown adipose tissue, better
      insulin sensitivity, increased intestinal gluconeogenesis and preservation of
      islets of Langerhans histomorphology and function. HFD-pairfat mice had a
      comparable improvement in insulin sensitivity, without changes in islets
      physiology or intestinal gluconeogenesis. Remarkably, both HFD-Leu and HFD
      pairfat mice had decreased hepatic lipid content, which likely helped improve
      insulin sensitivity. In contrast, when leucine was supplemented to already obese
      animals, no changes in body weight, body composition or glucose metabolism were
      observed. CONCLUSIONS/SIGNIFICANCE: These findings suggest that leucine improves
      insulin sensitivity in HFD-fed mice by primarily decreasing adiposity, rather
      than directly acting on peripheral target organs. However, beneficial effects of
      leucine on intestinal gluconeogenesis and islets of Langerhans's physiology might
      help prevent type 2 diabetes development. Differently, metabolic benefit of
      leucine supplementation is lacking in already obese animals, a phenomenon
      possibly related to the extent of the obesity before starting the
      supplementation.

PMID- 24086366
TI  - Seasonal effects of UCP1 gene polymorphism on visceral fat accumulation in
      Japanese adults.
AB  - Uncoupling protein 1 (UCP1) and beta3 adrenergic receptor (ADRB3) genes play
      central roles in the thermogenesis of brown adipose tissue (BAT) in adult humans.
      However, the importance of single-nucleotide polymorphisms (SNPs) in both genes
      during the development of obesity is controversial. Although active BAT in adult
      humans is frequently observed in the winter season, the effects of sampling
      season have not been taken into consideration in previous association studies.
      Here, we tested the associations of UCP1 -3826A/G and ADRB3 Trp64Arg with body
      mass index (BMI) and visceral fat area (VFA) in 3013 Japanese adults sampled
      during different seasons. Association between SNPs and the obesity-related traits
      were assessed using multiple linear regression models, including sex, age,
      physical activity, and genotypes. Both SNPs did not show significant associations
      in the models based on the entire cohort. However, in subsets comprising
      individuals mainly sampled from winter to spring, UCP1 showed significant
      associations with VFA (P = 0.0098) and VFA adjusted for BMI (P = 0.0128).
      Moreover, the effects of UCP1 on VFA were strongly negatively correlated with
      outdoor temperature (P = 0.00011), but not with night length (P = 0.039). ADRB3
      did not show these associations, but an additive effect with UCP1 was observed
      for VFA adjusted for BMI (P = 0.0067). Subsets sampled in the hot season did not
      show significant associations for both SNPs. The season-specific effects of UCP1
      on VFA were consistent with a previous finding that active BAT was more
      frequently found in winter than in summer, and supported the importance of cold
      stress in BAT activation and the significance of BAT in the development of
      obesity in adult humans.

PMID- 24086367
TI  - In silico and in vivo anti-malarial studies of 18beta glycyrrhetinic acid from
      Glycyrrhiza glabra.
AB  - Malaria is one of the most prevailing fatal diseases causing between 1.2 and 2.7
      million deaths all over the world each year. Further, development of resistance
      against the frontline anti-malarial drugs has created an alarming situation,
      which requires intensive drug discovery to develop new, more effective,
      affordable and accessible anti-malarial agents possessing novel modes of action.
      Over the past few years triterpenoids from higher plants have shown a wide range
      of anti-malarial activities. As a part of our drug discovery program for anti
      malarial agents from Indian medicinal plants, roots of Glycyrrhizaglabra were
      chemically investigated, which resulted in the isolation and characterization of
      18beta-glycyrrhetinic acid (GA) as a major constituent. The in vitro studies
      against P. falciparum showed significant (IC50 1.69 ug/ml) anti-malarial
      potential for GA. Similarly, the molecular docking studies showed adequate
      docking (LibDock) score of 71.18 for GA and 131.15 for standard anti-malarial
      drug chloroquine. Further, in silico pharmacokinetic and drug-likeness studies
      showed that GA possesses drug-like properties. Finally, in vivo evaluation showed
      a dose dependent anti-malarial activity ranging from 68-100% at doses of 62.5-250
      mg/kg on day 8. To the best of our knowledge this is the first ever report on the
      anti-malarial potential of GA. Further work on optimization of the anti-malarial
      lead is under progress.

PMID- 24086368
TI  - An epistatic interaction between the PAX8 and STK17B genes in papillary thyroid
      cancer susceptibility.
AB  - Papillary Thyroid Cancer (PTC) is a heterogeneous and complex disease;
      susceptibility to PTC is influenced by the joint effects of multiple common, low
      penetrance genes, although relatively few have been identified to date. Here we
      applied a rigorous combined approach to assess both the individual and epistatic
      contributions of genetic factors to PTC susceptibility, based on one of the
      largest series of thyroid cancer cases described to date. In addition to
      identifying the involvement of TSHR variation in classic PTC, our pioneer study
      of epistasis revealed a significant interaction between variants in STK17B and
      PAX8. The interaction was detected by MD-MBR (p = 0.00010) and confirmed by other
      methods, and then replicated in a second independent series of patients (MD-MBR p
      = 0.017). Furthermore, we demonstrated an inverse correlation between expression
      of PAX8 and STK17B in a set of cell lines derived from human thyroid carcinomas.
      Overall, our work sheds additional light on the genetic basis of thyroid cancer
      susceptibility, and suggests a new direction for the exploration of the inherited
      genetic contribution to disease using association studies.

PMID- 24086369
TI  - Anti-aquaporin-1 autoantibodies in patients with neuromyelitis optica spectrum
      disorders.
AB  - Autoantibodies against aquaporin-4 (AQP4), a water channel in CNS astrocytes, are
      detected in ~50-80% of patients with neuromyelitis optica spectrum disorders
      (NMOsd), characterized by longitudinally extensive transverse myelitis (LETM)
      and/or optic neuritis. Although these autoantibodies present an invaluable
      biomarker for NMOsd and for the differential diagnosis of multiple sclerosis
      (MS), diagnosis of anti-AQP4-seronegative NMOsd remains challenging. We
      hypothesized that seronegative NMOsd patients might have autoantibodies against
      aquaporin-1 (AQP1), another water channel in CNS astrocytes. We initially
      developed a radioimmunoprecipitation assay to search for anti-AQP1 antibodies in
      sera from 632 individuals. Anti-AQP1 or anti-AQP4 autoantibodies were detected in
      16.7% and 12%, respectively, of 348 patients with suspected NMOsd. Anti-AQP1
      specificity was confirmed by competition, protein immunoblotting and ELISA
      assays, whereas epitope localization was studied by immunoadsorption on intact
      cells expressing AQP1 and peptide mapping experiments. Most anti-AQP1
      autoantibodies were of the complement-activating IgG1 subclass and the majority
      bound to the extracellular domain of AQP1, suggesting a possible pathogenic role.
      Five out of 42 MS patients had anti-AQP1 antibodies, but 2 of them also had
      spinal cord lesions, while the anti-AQP1 antibodies in the other 3 bound to the
      cytoplasmic domain of AQP1. Anti-AQP1 antibodies were not detected in 100 healthy
      individuals or 142 patients with non-demyelinating neuroimmune diseases. Analysis
      of 17 anti-AQP1+/anti-AQP4- patients with suspected NMOsd showed that 5 had NMO
      and 11 had LETM. 12/17 of these sera bound predominantly to the extracellular
      AQP1 loop-Alpha. Overall, we found that anti-AQP1 autoantibodies are present in a
      subgroup of patients with chronic demyelination in the CNS and similarities with
      anti-AQP4-seronegative NMOsd, offering a novel potential biomarker for CNS
      demyelination disorders. 

PMID- 24086370
TI  - Impact of glutathione-S-transferases (GST) polymorphisms and hypermethylation of
      relevant genes on risk of prostate cancer biochemical recurrence: a meta
      analysis.
AB  - INTRODUCTION: Accurate prediction of the biochemical recurrence (BCR) is critical
      for patients after intended curative therapy like radical prostatectomy (RP) or
      definitive radiotherapy for prostate cancer. Glutathione-S-transferases
      polymorphisms as well as hypermethylation of GSTP1 and functional genes in
      carcinogenesis, including tumor suppression gene (APC), hormone receptor that
      regulates cell growth and differentiation gene (RARbeta) were reported to be
      associated with BCR. Nevertheless, the reported results are inconsistent. To
      evaluate the relationship between glutathione-S-transferases polymorphisms and
      hypermethylation of these genes and the risk of prostate cancer BCR, we carried
      out a meta-analysis of the published studies. METHODS AND MATERIALS: We performed
      a search in Medline, Embase and CNKI database with GST, APC, RARbeta in
      combination with single nucleotide polymorphism, hypermethylation, prostate
      cancer and recurrence. Languages were restricted to English and Chinese. RESULTS:
      Our study included 4 case-control studies and 7 cohort studies including 12 data
      sets and 3,037 prostate cancer patients. We confirmed that APC hypermethylation
      is associated with a modest hazard for biochemical recurrence after RP (HR =
      1.85, 95%CI = 1.12-3.06). We also suggest GSTP1 polymorphism and CpG
      hypermethylation tested in serum are associated with BCR (HR = 1.94, 95%CI = 1.13
      3.34). We also identified a possible association between GSTM1 null polymorphism
      and prostate cancer biochemical recurrence risk with borderline significance (HR
      = 1.29, 95%CI = 0.97-1.71). CONCLUSION: To our knowledge, this is the first meta
      analysis evaluating the relationship of polymorphisms and hypermethylation in
      GSTs and biochemical recurrence. GSTM1, GSTP1 polymorphisms and hypermethylation
      of GSTP1, APC may be potential biomarkers for the evaluation of the probability
      of BCR. Further studies are warranted to validate these findings in larger
      cohorts with longer follow-up.

PMID- 24086371
TI  - White matter abnormalities and structural hippocampal disconnections in amnestic
      mild cognitive impairment and Alzheimer's disease.
AB  - The purpose of this project was to evaluate white matter degeneration and its
      impact on hippocampal structural connectivity in patients with amnestic mild
      cognitive impairment, non-amnestic mild cognitive impairment and Alzheimer's
      disease. We estimated white matter fractional anisotropy, mean diffusivity and
      hippocampal structural connectivity in two independent cohorts. The ADNI cohort
      included 108 subjects [25 cognitively normal, 21 amnestic mild cognitive
      impairment, 47 non-amnestic mild cognitive impairment and 15 Alzheimer's
      disease]. A second cohort included 34 subjects [15 cognitively normal and 19
      amnestic mild cognitive impairment] recruited in Montreal. All subjects underwent
      clinical and neuropsychological assessment in addition to diffusion and T1 MRI.
      Individual fractional anisotropy and mean diffusivity maps were generated using
      FSL-DTIfit. In addition, hippocampal structural connectivity maps expressing the
      probability of connectivity between the hippocampus and cortex were generated
      using a pipeline based on FSL-probtrackX. Voxel-based group comparison statistics
      of fractional anisotropy, mean diffusivity and hippocampal structural
      connectivity were estimated using Tract-Based Spatial Statistics. The proportion
      of abnormal to total white matter volume was estimated using the total volume of
      the white matter skeleton. We found that in both cohorts, amnestic mild cognitive
      impairment patients had 27-29% white matter volume showing higher mean
      diffusivity but no significant fractional anisotropy abnormalities. No fractional
      anisotropy or mean diffusivity differences were observed between non-amnestic
      mild cognitive impairment patients and cognitively normal subjects. Alzheimer's
      disease patients had 66.3% of normalized white matter volume with increased mean
      diffusivity and 54.3% of the white matter had reduced fractional anisotropy.
      Reduced structural connectivity was found in the hippocampal connections to
      temporal, inferior parietal, posterior cingulate and frontal regions only in the
      Alzheimer's group. The severity of white matter degeneration appears to be higher
      in advanced clinical stages, supporting the construct that these abnormalities
      are part of the pathophysiological processes of Alzheimer's disease. 

PMID- 24086372
TI  - Tropine forming tropinone reductase gene from Withania somnifera (Ashwagandha):
      biochemical characteristics of the recombinant enzyme and novel physiological
      overtones of tissue-wide gene expression patterns.
AB  - Withania somnifera is one of the most reputed medicinal plants of Indian systems
      of medicine synthesizing diverse types of secondary metabolites such as
      withanolides, alkaloids, withanamides etc. Present study comprises cloning and E.
      coli over-expression of a tropinone reductase gene (WsTR-I) from W. somnifera,
      and elucidation of biochemical characteristics and physiological role of
      tropinone reductase enzyme in tropane alkaloid biosynthesis in aerial tissues of
      the plant. The recombinant enzyme was demonstrated to catalyze NADPH-dependent
      tropinone to tropine conversion step in tropane metabolism, through TLC, GC and
      GC-MS-MS analyses of the reaction product. The functionally active homodimeric
      ~60 kDa enzyme catalyzed the reaction in reversible manner at optimum pH 6.7.
      Catalytic kinetics of the enzyme favoured its forward reaction (tropine
      formation). Comparative 3-D models of landscape of the enzyme active site
      contours and tropinone binding site were also developed. Tissue-wide and
      ontogenic stage-wise assessment of WsTR-I transcript levels revealed constitutive
      expression of the gene with relatively lower abundance in berries and young
      leaves. The tissue profiles of WsTR-I expression matched those of tropine levels.
      The data suggest that, in W. somnifera, aerial tissues as well possess tropane
      alkaloid biosynthetic competence. In vivo feeding of U-[(14)C]-sucrose to orphan
      shoot (twigs) and [(14)C]-chasing revealed substantial radiolabel incorporation
      in tropinone and tropine, confirming the de novo synthesizing ability of the
      aerial tissues. This inherent independent ability heralds a conceptual novelty in
      the backdrop of classical view that these tissues acquire the alkaloids through
      transportation from roots rather than synthesis. The TR-I gene expression was
      found to be up-regulated on exposure to signal molecules (methyl jasmonate and
      salicylic acid) and on mechanical injury. The enzyme's catalytic and structural
      properties as well as gene expression profiles are discussed with respect to
      their physiological overtones.

PMID- 24086373
TI  - Mating behaviour and copulatory mechanism in the scorpionfly Neopanorpa
      longiprocessa (Mecoptera: Panorpidae).
AB  - Sexual conflict during copulation may drive morphological and behavioral
      evolution in insects. Although nuptial feeding behaviour is well studied in
      Panorpa, whether this behaviour is universal in Panorpidae remains unknown. The
      scorpionfly Neopanorpa longiprocessa Hua & Chou, 1997 was investigated for its
      mating behaviour, functional morphology of the notal organ, and external
      genitalia using light microscopy and scanning electron microscopy. The results
      show that the mating behaviour is not associated with nuptial feeding in N.
      longiprocessa. The morphological basis of this non-nuptial copulation is likely
      related to the developed notal organ of the male. The notal organ serves a
      function to seize wings of the female during copulation. Only males that succeed
      in seizing the female with the notal organ are able to establish genital contact
      and copulate. The male genitalia exhibit distinct species-specific modification.
      The epandrium (tergum IX) has evolved a pair of ventral bulbs to grasp the
      subgenital plate of the female. The hypandrium (sternum IX) has a pair of dorsal
      processes to control the abdominal end of the female. These results indicate that
      nuptial feeding is not a universal behaviour in Panorpidae. Presumably, these
      grasping apparatuses compensate the scorpionflies that fail to provide nuptial
      gifts, as exemplified by N. longiprocessa. 

PMID- 24086374
TI  - Antagonism of betulinic acid on LPS-mediated inhibition of ABCA1 and cholesterol
      efflux through inhibiting nuclear factor-kappaB signaling pathway and miR-33
      expression.
AB  - ATP-binding cassette transporter A1 (ABCA1) is critical in exporting cholesterol
      from macrophages and plays a protective role in the development of
      atherosclerosis. The purpose of this study was to investigate the effects of
      betulinic acid (BA), a pentacyclic triterpenoid, on ABCA1 expression and
      cholesterol efflux, and to further determine the underlying mechanism. BA
      promoted ABCA1 expression and cholesterol efflux, decreased cellular cholesterol
      and cholesterol ester content in LPS-treated macrophages. Furthermore, we found
      that BA promoted ABCA1 expression via down-regulation of miR-33s. The inhibition
      of LPS-induced NF-kappaB activation further decreased miR-33s expression and
      enhanced ABCA1 expression and cholesterol efflux when compared with BA only
      treatment. In addition, BA suppressed IkappaB phosphorylation, p65
      phosphorylation and nuclear translocation, and the transcription of NF-kappaB
      dependent related gene. Moreover, BA reduced atherosclerotic lesion size, miR-33s
      levels and NF-kappaB activation, and promoted ABCA1 expression in apoE(-/-) mice.
      Taken together, these results reveal a novel mechanism for the BA-mediated ABCA1
      expression, which may provide new insights for developing strategies for
      modulating vascular inflammation and atherosclerosis. 

PMID- 24086375
TI  - SMG6 cleavage generates metastable decay intermediates from nonsense-containing
      beta-globin mRNA.
AB  - mRNAs targeted by endonuclease decay generally disappear without detectable decay
      intermediates. The exception to this is nonsense-containing human beta-globin
      mRNA, where the destabilization of full-length mRNA is accompanied by the
      cytoplasmic accumulation of 5'-truncated transcripts in erythroid cells of
      transgenic mice and in transfected erythroid cell lines. The relationship of the
      shortened RNAs to the decay process was characterized using an inducible
      erythroid cell system and an assay for quantifying full-length mRNA and a
      truncated RNA missing 169 nucleotides from the 5' end. In cells knocked down for
      Upf1 a reciprocal increase in full-length and decrease in shortened RNA confirmed
      the role of NMD in this process. Kinetic analysis demonstrated that the 5'
      truncated RNAs are metastable intermediates generated during the decay process.
      SMG6 previously was identified as an endonuclease involved in NMD. Consistent
      with involvement of SMG6 in the decay process full-length nonsense-containing
      beta-globin mRNA was increased and the Delta169 decay intermediate was decreased
      in cells knocked down for SMG6. This was reversed by complementation with siRNA
      resistant SMG6, but not by SMG6 with inactivating PIN domain mutations.
      Importantly, none of these altered the phosphorylation state of Upf1. These data
      provide the first proof for accumulation of stable NMD products by SMG6
      endonuclease cleavage. 

PMID- 24086376
TI  - Characterization and phylogenetic analysis of the mitochondrial genome of Glarea
      lozoyensis indicates high diversity within the order Helotiales.
AB  - BACKGROUND: Glarea lozoyensis is a filamentous fungus used for the industrial
      production of non-ribosomal peptide pneumocandin B0. In the scope of a whole
      genome sequencing the complete mitochondrial genome of the fungus has been
      assembled and annotated. It is the first one of the large polyphyletic
      Helotiaceae family. A phylogenetic analysis was performed based on conserved
      proteins of the oxidative phosphorylation system in mitochondrial genomes.
      RESULTS: The total size of the mitochondrial genome is 45,038 bp. It contains the
      expected 14 genes coding for proteins related to oxidative phosphorylation,two
      rRNA genes, six hypothetical proteins, three intronic genes of which two are
      homing endonucleases and a ribosomal protein rps3. Additionally there is a set of
      33 tRNA genes. All genes are located on the same strand. Phylogenetic analyses
      based on concatenated mitochondrial protein sequences confirmed that G.
      lozoyensis belongs to the order of Helotiales and that it is most closely related
      to Phialocephala subalpina. However, a comparison with the three other
      mitochondrial genomes known from Helotialean species revealed remarkable
      differences in size, gene content and sequence. Moreover, it was found that the
      gene order found in P. subalpina and Sclerotinia sclerotiorum is not conserved in
      G. lozoyensis. CONCLUSION: The arrangement of genes and other differences found
      between the mitochondrial genome of G. lozoyensis and those of other Helotiales
      indicates a broad genetic diversity within this large order. Further
      mitochondrial genomes are required in order to determine whether there is a
      continuous transition between the different forms of mitochondrial genomes or G.
      lozoyensis belongs to a distinct subgroup within Helotiales.

PMID- 24086377
TI  - Matrix metalloproteinase-9 expression by Hodgkin-Reed-Sternberg cells is
      associated with reduced overall survival in young adult patients with classical
      Hodgkin lymphoma.
AB  - Previous studies have investigated the prognostic relevance of MMP9 in classical
      Hodgkin lymphoma (cHL), with negative results. However, we have found that MMP9
      immunoistochemical expression by Hodgkin-Reed-Sternberg cells is associated with
      reduced overall survival in a subset of young adult Brazilian patients diagnosed
      with cHL. Additionally, we have observed that MMP9 expression by neoplastic cells
      in cHL is associated with EBV positivity. These results may support a rational
      basis for additional studies on the role of this metalloproteinase as a target
      for therapy in classical Hodgkin lymphoma. 

PMID- 24086378
TI  - Novel pathways for injury from offshore oil spills: direct, sublethal and
      indirect effects of the Deepwater Horizon oil spill on pelagic Sargassum
      communities.
AB  - The pelagic brown alga Sargassum forms an oasis of biodiversity and productivity
      in an otherwise featureless ocean surface. The vast pool of oil resulting from
      the Deepwater Horizon oil spill came into contact with a large portion of the
      Gulf of Mexico's floating Sargassum mats. Aerial surveys performed during and
      after the oil spill show compelling evidence of loss and subsequent recovery of
      Sargassum. Expanding on the trends observed in the aerial surveys, we conducted a
      series of mesocosm experiments to test the effect of oil and dispersants on the
      vertical position and weight of the Sargassum complex (Sargassum natans and S.
      fluitans), as well as on the dissolved oxygen concentrations surrounding the
      algae. Dispersant and dispersed-oil had significant effects on the vertical
      position of both species of Sargassum over a period of 72 hours. Similarly,
      dissolved oxygen concentrations were lowest in dispersant and dispersed-oil
      treatments, respectively. Cumulatively, our findings suggest three pathways for
      oil-spill related injury: (1) Sargassum accumulated oil on the surface exposing
      animals to high concentrations of contaminants; (2) application of dispersant
      sank Sargassum, thus removing the habitat and potentially transporting oil and
      dispersant vertically; and (3) low oxygen surrounded the habitat potentially
      stressing animals that reside in the alga. These pathways represent direct,
      sublethal, and indirect effects of oil and dispersant release that minimize the
      ecosystem services provided by floating Sargassum - the latter two effects are
      rarely considered in assessing impacts of oil spills or response procedures. 

PMID- 24086379
TI  - Vaccination of koalas with a recombinant Chlamydia pecorum major outer membrane
      protein induces antibodies of different specificity compared to those following a
      natural live infection.
AB  - Chlamydial infection in koalas is common across the east coast of Australia and
      causes significant morbidity, infertility and mortality. An effective vaccine to
      prevent the adverse consequences of chlamydial infections in koalas (particularly
      blindness and infertility in females) would provide an important management tool
      to prevent further population decline of this species. An important step towards
      developing a vaccine in koalas is to understand the host immune response to
      chlamydial infection. In this study, we used the Pepscan methodology to identify
      B cell epitopes across the Major Outer Membrane Protein (MOMP) of four C. pecorum
      strains/genotypes that are recognized, either following (a) natural live
      infection or (b) administration of a recombinant MOMP vaccine. Plasma antibodies
      from the koalas naturally infected with a C. pecorum G genotype strain recognised
      the epitopes located in the variable domain (VD) four of MOMP G and also VD4 of
      MOMP H. By comparison, plasma antibodies from an animal infected with a C.
      pecorum F genotype strain recognised epitopes in VD1, 2 and 4 of MOMP F, but not
      from other genotype MOMPs. When Chlamydia-free koalas were immunised with
      recombinant MOMP protein they produced antibodies not only against epitopes in
      the VDs but also in conserved domains of MOMP. Naturally infected koalas
      immunised with recombinant MOMP protein also produced antibodies against epitopes
      in the conserved domains. This work paves the way for further refinement of a
      MOMP-based Chlamydia vaccine that will offer wide cross-protection against the
      variety of chlamydial infections circulating in wild koala populations. 

PMID- 24086380
TI  - Female snub-nosed monkeys exchange grooming for sex and infant handling.
AB  - Allogrooming in primates has acquired an important social function beyond its
      original hygienic function and can be exchanged either for itself or used as a
      currency to obtain other benefits such as copulations, access to infants or
      agonistic support. We explore the strategic use of grooming as a social tool in
      semi-wild golden snub-nosed monkeys (Rhinopithecus roxellana) in central China, a
      species where two desirable resources, viz. reproductive males and infants, are
      restricted to the mating and birth season, respectively. We predict that females
      expend their grooming selectively to different individuals according to their
      "value". Our results show that in the mating season, females devoted more
      grooming to the resident male than in the birth season, and this effect was
      particularly strong in non-mothers (females without newborn infants). Moreover,
      females were more likely to groom the resident male after copulation than during
      baseline social conditions. In the birth season, females devoted more grooming to
      other females than in the mating season, and mothers (females with newborn
      infants) were the most valuable grooming partners. The mean rate of contact by
      non-mothers toward infants of other females was significantly higher after
      grooming the mothers than in baseline social conditions. In conclusion, our
      findings lend credence to the notion that primate females use grooming as a
      strategic tool to obtain limited resources such as males and infants and vary
      preference for particular individuals depending on the seasonal availability of
      valuable resources. 

PMID- 24086381
TI  - Comparison of expansive pedicle screw and polymethylmethacrylate-augmented
      pedicle screw in osteoporotic sheep lumbar vertebrae: biomechanical and
      interfacial evaluations.
AB  - BACKGROUND: It was reported that expansive pedicle screw (EPS) and
      polymethylmethacrylate-augmented pedicle screw (PMMA-PS) could be used to
      increase screw stability in osteoporosis. However, there are no studies comparing
      the two kinds of screws in vivo. Thus, we aimed to compare biomechanical and
      interfacial performances of EPS and PMMA-PS in osteoporotic sheep spine.
      METHODOLOGY/PRINCIPAL FINDINGS: After successful induction of osteoporotic sheep,
      lumbar vertebrae in each sheep were randomly divided into three groups. The
      conventional pedicle screw (CPS) was inserted directly into vertebrae in CPS
      group; PMMA was injected prior to insertion of CPS in PMMA-PS group; and the EPS
      was inserted in EPS group. Sheep were killed and biomechanical tests, micro-CT
      analysis and histological observation were performed at both 6 and 12 weeks post
      operation. At 6-week and 12-week, screw stabilities in EPS and PMMA-PS groups
      were significantly higher than that in CPS group, but there were no significant
      differences between EPS and PMMA-PS groups at two study periods. The screw
      stability in EPS group at 12-week was significantly higher than that at 6-week.
      The bone trabeculae around the expanding anterior part of EPS were more and
      denser than that in CPS group at 6-week and 12-week. PMMA was found without any
      degradation and absorption forming non-biological "screw-PMMA-bone" interface in
      PMMA-PS group, however, more and more bone trabeculae surrounded anterior part of
      EPS improving local bone quality and formed biological "screw-bone" interface.
      CONCLUSIONS/SIGNIFICANCE: EPS can markedly enhance screw stability with a similar
      effect to the traditional method of screw augmentation with PMMA in initial
      surgery in osteoporosis. EPS can form better biological interface between screw
      and bone than PMMA-PS. In addition, EPS have no risk of thermal injury, leakage
      and compression caused by PMMA. We propose EPS has a great application potential
      in augmentation of screw stability in osteoporosis in clinic.

PMID- 24086382
TI  - Public views on food addiction and obesity: implications for policy and
      treatment.
AB  - BACKGROUND: According to their advocates, neurobiological explanations of
      overeating, or "food addiction", have the potential to impact public
      understanding and treatment of obesity. In this study, we examine the public's
      acceptance of the concept of food addiction as an explanation of overeating and
      assess its effects upon their attitudes toward obese persons and the treatment of
      obesity. METHODS AND FINDINGS: We conducted an online survey of 479 adults from
      the US (n = 215) and Australia (n = 264). There was substantial support for the
      idea of food addiction, particularly among obese participants. Over half favoured
      treating obesity as a type of addiction. Psychotherapy was believed to be the
      most effective treatment and educational and support programs were the preferred
      policies to address food addiction. There was very little support for increasing
      taxes on obesogenic foods. Despite the strong support for seeing obesity as a
      form of addiction, respondents still saw obesity as primarily the result of
      personal choices and emphasized the need for individuals to take responsibility
      for their eating. CONCLUSIONS: Our sample of the general public strongly
      supported the idea of obesity as a form of food addiction; but this did not
      translate into support of clinical and public health policies that experts
      believe are most likely to reduce the prevalence of obesity. The reasons for the
      apparent disjunction between support for food addiction and a strong emphasis on
      personal choice for weight warrant further examination.

PMID- 24086383
TI  - Mothers of autistic children: lower plasma levels of oxytocin and Arg-vasopressin
      and a higher level of testosterone.
AB  - BACKGROUND: Autism is a pervasive neurodevelopmental disorder,thought to be
      caused by a combination of genetic heritability and environmental risk factors.
      Some autistic-like traits have been reported in mothers of autistic children. We
      hypothesized that dysregulation of oxytocin (OXT), Arg-vasopressin (AVP) and sex
      hormones, found in autistic children, may also exist in their mothers. METHODS:
      We determined plasma levels of OXT (40 in autism vs. 26 in control group), AVP
      (40 vs. 17) and sex hormones (61 vs. 47) in mothers of autistic and normal
      children by enzyme immunoassay and radioimmunoassay, respectively and
      investigated their relationships with the children's autistic behavior scores
      (Childhood Autism Rating Scale (CARS) and Autism Behavior Checklist (ABC)).
      RESULTS: Significantly lower plasma concentrations of OXT (p<0.001) and AVP
      (p<0.001), as well as a higher level of plasma testosterone (p<0.05), were found
      in mothers of autistic children vs. those of control. The children's autistic
      behavior scores were negatively associated with maternal plasma levels of OXT and
      AVP. CONCLUSIONS: These results suggest that dysregulation of OXT, AVP and/or
      testosterone systems exist in mothers of autistic children, which may impact
      children's susceptibility to autism.

PMID- 24086384
TI  - Lactate dehydrogenase 5 expression in Non-Hodgkin lymphoma is associated with the
      induced hypoxia regulated protein and poor prognosis.
AB  - Lactate dehydrogenase 5 (LDH-5) is one of the major isoenzymes catalyzing the
      biochemical process of pyruvate to lactate. The purpose of this study was to
      investigate the expression of serum LDH-5 and test whether this enzyme is
      regulated by tumor hypoxia and represents a prognostic marker in patients with
      Non-Hodgkin's lymphoma (NHL). In this study, LDH-5 levels were detected using
      agarose gel electrophoresis in NHL patients (n = 266) and non-NHL controls
      including benign lymphadenectasis (n = 30) and healthy cohorts (n = 233). We also
      explored the expression of LDH-5 and hypoxia-inducible factor (HIF) 1alpha in NHL
      and benign controls by immunohistochemistry and immunofluorescence staining,
      respectively. Moreover, the role of LDH-5 in the progression of NHL was assessed
      by multivariate Cox analyses and Kaplan-Meier survival estimates. Serum
      concentrations of LDH-5 were significantly higher in NHL patients (9.3%) than in
      benign patients and healthy controls (7.5% and 7.2%, respectively, P<0.01).
      Application of LDH-5 detection increased the sensitivity of NHL detection,
      identifying 53.4% of NHL patients as positive, compared with the measurement of
      total LDH levels (36.5% sensitivity). LDH-5 concentrations increased with
      clinical stage, extra-nodal site involvement, and WHO performance status of
      patients with NHL. Exposure to a hypoxic environment induced the expression of
      LDH-5 and its overexpression correlated with HIF1alpha cytoplasmic accumulation
      in NHL cells. In multivariate analyses, LDH-5 was an independent marker for
      progression-free survival in patients with NHL (P<0.001). Overall, the expression
      of LDH-5 was elevated in NHL, showing an association with tumor hypoxia and
      unfavorable prognosis. Thus, LDH-5 emerges as a promising prognostic predictor
      for NHL patients.

PMID- 24086385
TI  - High antibody-dependent cellular cytotoxicity responses are correlated with
      strong CD8 T cell viral suppressive activity but not with B57 status in HIV-1
      elite controllers.
AB  - The role of Antibody-dependent cellular cytotoxicity (ADCC) responses in HIV-1
      controllers is still unclear due to the heterogeneity of these patients. We
      analyzed 67 HIV-1 controllers and found significantly higher levels of ADCC
      antibodies in controllers versus viremic subjects (p = 0.017). Moreover,
      multivariate analysis revealed significantly higher ADCC titers in HLA B57-
      controllers compared to HLA-B57+ ones (p = 0.0086). These data suggest a role for
      ADCC in immune control of HIV, especially in HLA B57 negative controllers.

PMID- 24086386
TI  - Abundances of demersal sharks and chimaera from 1994-2009 scientific surveys in
      the central Mediterranean Sea.
AB  - Bibliographic and data gathered in scientific bottom trawl surveys carried out
      off the Southern Coasts of Sicily (Mediterranean Sea), from 1994 to 2009 and
      between a depth of 10 and 800 m, were analysed in order to prepare a checklist of
      demersal sharks and chimaera, which are species sensitive to fisheries
      exploitation. Out of the 27 previously reported demersal shark and chimaera taxa
      in the Mediterranean, only 23 were found in literature and 20 sampled during the
      surveys in the investigated area. Among the species sampled in the surveys, only
      2 ubiquitous (Squalusblainville and Scyliorhinuscanicula) and 3 deep-water
      (Chimaeramonstrosa , Centrophorusgranulosus and Galeusmelastomus) species showed
      a wide geographical distribution with a consistent abundance. Excluding the rare
      (such as Oxynotuscentrina) or uncommon shark (e.g. Squalusacanthias), the
      estimated frequencies of occurrence and abundance indexes show a possible risk of
      local extinction for the almost exclusively (e.g. angelshark, Squatina spp.) or
      preferential (e.g. Scyliorhinusstellaris) neritic species. 

PMID- 24086387
TI  - Natural carbon isotope abundance of plasma metabolites and liver tissue differs
      between diabetic and non-diabetic Zucker diabetic fatty rats.
AB  - BACKGROUND: 'You are what you eat' is an accurate summary for humans and animals
      when it comes to carbon isotope abundance. In biological material,
      natural(13)C/(12)C ratio is subject to minute variations due to diet composition
      (mainly from ingestion of C3 and C4 metabolism plants) and to the discrimination
      between 'light' and 'heavy' isotopes during biochemical reactions (isotope
      effects and isotopic fractionation). METHODOLOGY/PRINCIPAL FINDINGS: Carbon
      isotopic abundance was measured in ZDF (fa/+) and ZDF (fa/fa), (lean and obese
      diabetic rats respectively) fed the same diet. By analysing plasma metabolites
      (glucose and non-esterified fatty acids), breath and liver tissue by high
      precision isotope ratio mass spectrometry, we demonstrate for the first time
      statistically distinguishable metabolic carbon isotope abundance between ZDF
      (fa/+) and ZDF (fa/fa) rats based on plasma glucose, palmitic, oleic, linoleic,
      arachidonic acids and bulk analysis of liver tissue (P<0.005) resulting into
      clear isotopic fingerprints using principal component analysis. We studied the
      variation of isotopic abundance between both groups for each metabolite and
      through the metabolic pathways using the precursor/product approach. We confirmed
      that lipids were depleted in (13)C compared to glucose in both genotypes. We
      found that isotopic abundance of linoleic acid (C18: 2n-6), even though both
      groups had the same feed, differed significantly between both groups. The likely
      reason for these changes between ZDF (fa/+) and ZDF (fa/fa) are metabolic
      dysregulation associated with various routing and fluxes of metabolites.
      CONCLUSION/SIGNIFICANCE: This work provides evidence that measurement of natural
      abundance isotope ratio of both bulk tissue and individual metabolites can
      provide meaningful information about metabolic changes either associated to
      phenotype or to genetic effects; irrespective of concentration. In the future
      measuring the natural abundance delta(13)C of key metabolites could be used as
      endpoints for studying in vivo metabolism, especially with regards to metabolic
      dysregulation, and development and progression of metabolic diseases.

PMID- 24086388
TI  - Increased risk of high-grade hemorrhage in cancer patients treated with
      gemcitabine: a meta-analysis of 20 randomized controlled trials.
AB  - PURPOSE: Gemcitabine, a third-generation anticancer agent, has been shown to be
      active in several solid tumors. High-grade hemorrhage (grade >= 3) has been
      reported with this drug, although the overall risk remains unclear. We conducted
      a meta-analysis of randomized controlled trials evaluating the incidence and risk
      of high-grade hemorrhage associated with gemcitabine. METHODS: Pubmed was
      searched for articles published from January 1, 1990 to December 31, 2012.
      Eligible studies included prospective randomized controlled phase II and III
      trials evaluating gemcitabine-based vs non-gemcitabine-based therapy in patients
      with solid tumors. Data on high-grade hemorrhage were extracted. Overall
      incidence rates, relative risk (RR), and 95% confidence intervals (CI) were
      calculated employing fixed- or random-effects models depending on the
      heterogeneity of included trials. RESULTS: A total of 6433 patients from 20
      trials were included. Among patients treated with gemcitabine-based chemotherapy,
      the overall incidence of high-grade hemorrhage was 1.7% (95%CI: 0.9-3.1%), and
      the RR of high-grade hemorrhage was 2.727 (95%CI: 1.581-4.702, p<0.001).
      Exploratory subgroup analysis revealed the highest RR of hemorrhage in non-small
      cell lung cancer (NSCLC) patients (RR: 3.234; 95%CI, 1.678-6.233; p<0.001), phase
      II trials (RR 7.053, 95%CI: 1.591-31.27; p = 0.01), trials reported during 2006
      2012 (RR: 3.750; 95%CI: 1.735-8.108, p<0.001) and gemcitabine used as single
      agent (RR 7.48; 95%CI: 0.78-71.92, p = 0.081). CONCLUSION: Gemcitabine is
      associated with a significant increase risk of high-grade hemorrhage in patients
      with solid tumors when compared with non-gemcitabine-based therapy.

PMID- 24086389
TI  - A re-interpretation of the Eocene anuran Thaumastosaurus based on microCT
      examination of a 'mummified' specimen.
AB  - What originally appeared to be only an external cast of an anuran 'mummy' from
      the Quercy Phosphorites (southwestern France) was described as Rana plicata
      during the 19th century. Its geographical provenance is only vaguely known;
      therefore its precise age within the Paleogene was uncertain. The taxon was
      erected on the basis of the external morphology of the specimen, which includes
      few diagnostic characters. As a further complication, the name Rana plicata was
      recently shown to be unavailable at the time of the description, and the name
      Rana cadurcorum was proposed as a replacement. In order to see whether internal
      features were fossilized, the fossil was CT scanned. This showed that a large
      part of the skeleton is preserved. Unexpectedly, the scans revealed that the
      skull of the mummy is almost identical to that of Thaumastosaurus gezei, another
      anuran from the late middle or late Eocene of the Quercy Phosphorites. The few
      observed differences are attributable to intraspecific and ontogenetic variation,
      and R. cadurcorum is a junior subjective synonym of T. gezei. The mummy is
      therefore probably from the same time interval as T. gezei. The latter was
      previously known only by its skull, but the mummy provides important information
      on the postcranial skeleton. Earlier assessments, based only on the skull, placed
      Thaumastosaurus close to South American hyloid anurans, but a new phylogenetic
      analysis including postcranial characters reveals ranoid affinities. This study
      exemplifies the usefulness of modern imaging technologies that allow non
      destructive study of previously inaccessible internal anatomical features. 

PMID- 24086390
TI  - Impact on infants' cognitive development of antenatal exposure to iron deficiency
      disorder and common mental disorders.
AB  - OBJECTIVES: The aim of this study was to examine the effects of antenatal
      exposure to iron deficiency anemia (IDA) and common mental disorders (CMD) on
      cognitive development of 6 months old infants in a developing country. METHODS: A
      prospective population-based study in a rural province in Vietnam, which enrolled
      pregnant women at 12-20 weeks gestation and followed them up with their infants
      until six months postpartum. Criteria for IDA were Hb <11 g/dL and serum ferritin
      <15 ng/mL. CMD symptoms were assessed by the Edinburgh Postnatal Depression Scale
      Vietnam validation. Infant cognitive development was assessed by Bayley Scales of
      Infant and Toddler Development, 3rd Ed. Path analyses were performed to determine
      the direct and indirect, partly or fully mediated, causal effects of the
      antenatal exposures. RESULTS: A total of 497 pregnant women were recruited, of
      those 378 women provided complete data which were included in the analyses.
      Statistically significant direct adverse effects of persistent antenatal IDA
      (estimated difference of -11.62 points; 95% CI -23.01 to -0.22) and antenatal CMD
      (-4.80 points; 95% CI: -9.40 to -0.20) on infant Bayley cognitive scores at six
      months were found. Higher birthweight, household wealth, and self-rated
      sufficient supply of breastmilk were associated with higher cognitive scores.
      Maternal age >30 years and primiparity had an indirect adverse effect on infants'
      Bayley cognitive scores. CONCLUSIONS: These findings suggest that antenatal IDA
      and CMD both have adverse effects on child cognitive development, which if
      unrecognized and unaddressed are likely to be lasting. It is crucial that both
      these risks are considered by policy makers, clinicians, and researchers seeking
      to improve child cognitive function in developing countries.

PMID- 24086391
TI  - Increased expression of complement regulators CD55 and CD59 on peripheral blood
      cells in patients with EAHEC O104:H4 infection.
AB  - BACKGROUND: An outbreak of Shiga Toxin 2 (Stx-2) producing enterohemorrhagic and
      enteroaggregative E.coli (EAHEC) O104H4 infection in May 2011 caused
      enterocolitis and an unprecedented high 22% rate of hemolytic uremic syndrome
      (HUS). The monoclonal anti-C5 antibody Eculizumab (ECU) has been used
      experimentally in EAHEC patients with HUS but treatment efficacy is uncertain.
      ECU can effectively prevent hemolysis in paroxysmal nocturnal hemoglobinuria
      (PNH) caused by a lack of complement-regulating CD55 and CD59 on blood cells. We
      hypothesized a low expression of CD55 and CD59, as seen in PNH, might correlate
      with HUS development in EAHEC patients. METHODS: 76 EAHEC patients (34 only
      gastrointestinal symptoms [GI], 23: HUS, 19: HUS and neurological symptoms
      [HUS/N]) and 12 healthy controls (HC) were tested for the expression of CD55 and
      CD59 on erythrocytes and leukocytes retrospectively. Additionally, the effect of
      Stx-2 on CD55 and CD59 expression on erythrocytes and leukocytes was studied ex
      vivo. RESULTS: CD55 expression on erythrocytes was similar in all patient groups
      and HC while CD59 showed a significantly higher expression in HUS and HUS/N
      patients compared to HC and the GI group. CD55 and CD59 expression on leukocytes
      and their subsets was significantly higher in all patient groups compared to HC
      regardless of treatment type. However, CD59 expression on erythrocytes was
      significantly higher in HUS and HUS/N patients treated combined with plasma
      separation (PS) and ECU compared to HC. Adding Stx-2 ex vivo had no effect on
      CD55 and CD59 expression on leukocytes from HC or patients. CONCLUSION: HUS
      evolved independently from CD55 and CD59 expression on peripheral blood cells in
      EAHEC O104:H4 infected patients. Our data do not support a role for CD55 and CD59
      in HUS development during EAHEC O104:H4 infection and point to a different
      mechanism within the complement system for HUS development in EAHEC patients.

PMID- 24086392
TI  - Ascitic microbiota composition is correlated with clinical severity in cirrhosis
      with portal hypertension.
AB  - Identification of pathogenic bacteria in ascites correlates with poor clinical
      outcomes. Ascites samples are commonly reported culture-negative, even where
      frank infection is indicated. Culture-independent methods have previously
      reported bacterial DNA in ascites, however, whether this represents viable
      bacterial populations has not been determined. We report the first application of
      16S rRNA gene pyrosequencing and quantitative PCR in conjunction with propidium
      monoazide sample treatment to characterise the viable bacterial composition of
      ascites. Twenty five cirrhotic patients undergoing paracentesis provided ascites.
      Samples were treated with propidium monoazide to exclude non-viable bacterial
      DNA. Total bacterial load was quantified by 16S rRNA Q-PCR with species identity
      and relative abundance determined by 16S rRNA gene pyrosequencing. Correlation of
      molecular microbiology data with clinical measures and diagnostic microbiology
      was performed. Viable bacterial signal was obtained in 84% of ascites samples,
      both by Q-PCR and pyrosequencing. Approximately 190,000 ribosomal pyrosequences
      were obtained, representing 236 species, including both gut and non gut
      associated species. Substantial variation in the species detected was observed
      between patients. Statistically significant relationships were identified between
      the bacterial community similarity and clinical measures, including ascitic
      polymorphonuclear leukocyte count and Child-Pugh class. Viable bacteria are
      present in the ascites of a majority of patients with cirrhosis including those
      with no clinical signs of infection. Microbiota composition significantly
      correlates with clinical measures. Entry of bacteria into ascites is unlikely to
      be limited to translocation from the gut, raising fundamental questions about the
      processes that underlie the development of spontaneous bacterial peritonitis. 

PMID- 24086393
TI  - Crater Lake Apoyo revisited--population genetics of an emerging species flock.
AB  - The polytypic Nicaraguan Midas cichlids (Amphilophus cf. citrinellus) have been
      established as a model system for studying the mechanisms of speciation and
      patterns of diversification in allopatry and sympatry. The species assemblage in
      Crater Lake Apoyo has been accepted as a textbook example for sympatric
      speciation. Here, we present a first comprehensive data set of population genetic
      (mtDNA & AFLPs) proxies of species level differentiation for a representative set
      of individuals of all six endemic Amphilophus species occurring in Crater Lake
      Apoyo. AFLP genetic differentiation was partitioned into a neutral and non
      neutral component based on outlier-loci detection approaches, and patterns of
      species divergence were explored with Bayesian clustering methods. Substantial
      levels of admixture between species were detected, indicating different levels of
      reproductive isolation between the six species. Analysis of neutral genetic
      variation revealed several A. zaliosus as being introgressed by an unknown
      contributor, hereby rendering the sympatrically evolving L. Apoyo flock
      polyphyletic. This is contrasted by the mtDNA analysis delivering a clear
      monophyly signal with Crater Lake Apoyo private haplotypes characterising all six
      described species, but also demonstrating different demographic histories as
      inferred from pairwise mismatch distributions. 

PMID- 24086394
TI  - Comparative immunogenicity of 7 and 13-valent pneumococcal conjugate vaccines and
      the development of functional antibodies to cross-reactive serotypes.
AB  - BACKGROUND: Protection against disease or colonization from serotypes related to
      those in pneumococcal conjugate vaccines (i.e. cross-protection) vary by
      serotype; the basis for this variation is not understood. The 13-valent
      pneumococcal conjugate vaccine (PCV13) replaced 7-valent conjugate (PCV7) in the
      USA in 2010 allowing assessment of PCV7 and PCV13 immunogenicity and functional
      cross-protection in vitro. METHODS: Post-primary, pre-booster and post-booster
      sera from American Indian children receiving exclusively PCV7 or PCV13 were
      collected. IgG was measured by ELISA for 13 vaccine serotypes; functional
      antibody was assessed by opsonophagocytic killing assays for serotypes 6A/B/C and
      19A/F. RESULTS: Post-primary IgG geometric mean concentrations (GMC) for
      serotypes 4 and 9V were lower in PCV13 recipients while 19F GMCs were higher.
      Only 19F differences persisted after receipt of the booster dose. Functional
      antibody activity was higher among PCV13 recipients for 6A, 6C, 19A and 19F
      (p<0.04), and among PCV7 recipients for 6B (p = 0.01). Following PCV7, functional
      antibodies to 6A but not 19A were observed. High levels of 6C functional activity
      were seen after PCV13 but not PCV7. CONCLUSIONS: Functional antibody activity
      against 6A/B/C and 19A/F suggest that PCV13 is likely to control the 19A disease
      and 6C disease remaining despite widespread use of PCV7.

PMID- 24086395
TI  - The hypoxia-inducible transcription factor ZNF395 is controlled by IKB kinase
      signaling and activates genes involved in the innate immune response and cancer.
AB  - Activation of the hypoxia inducible transcription factor HIF and the NF-KB
      pathway promotes inflammation-mediated tumor progression. The cellular
      transcription factor ZNF395 has repeatedly been found overexpressed in various
      human cancers, particularly in response to hypoxia, implying a functional
      relevance. To understand the biological activity of ZNF395, we identified target
      genes of ZNF395 through a genome-wide expression screen. Induced ZNF395
      expression led to the upregulation of genes known to play a role in cancer as
      well as a subset of interferon (IFN)-stimulated genes (ISG) involved in antiviral
      responses such as IFIT1/ISG56, IFI44 and IFI16. In cells that lack ZNF395, the
      IFN-alpha-mediated stimulation of these factors was impaired, demonstrating that
      ZNF395 is required for the full induction of these antiviral genes. Transient
      transfections revealed that ZNF395-mediated activation of the IFIT1/ISG56
      promoter depends on the two IFN-stimulated response elements within the promoter
      and on the DNA-binding domain of ZNF395, a so-called C-clamp. We also show that
      IKBalpha kinase (IKK)-signaling is necessary to allow ZNF395 to activate
      transcription and simultaneously enhances its proteolytic degradation. Thus,
      ZNF395 becomes activated at the level of protein modification by IKK. Moreover,
      we confirm that the expression of ZNF395 is induced by hypoxia. Our results
      characterize ZNF395 as a novel factor that contributes to the maximal stimulation
      of a subset of ISGs. This transcriptional activity depends on IKK signaling
      further supporting a role of ZNF395 in the innate immune response. Given these
      results it is possible that under hypoxic conditions, elevated levels of ZNF395
      may support inflammation and cancer progression by activating the target genes
      involved in the innate immune response and cancer. 

PMID- 24086396
TI  - Huperzine A for Alzheimer's disease: a systematic review and meta-analysis of
      randomized clinical trials.
AB  - BACKGROUND: Huperzine A is a Chinese herb extract used for Alzheimer's disease.
      We conducted this review to evaluate the beneficial and harmful effect of
      Huperzine A for treatment of Alzheimer's disease. METHODS: We searched for
      randomized clinical trials (RCTs) of Huperzine A for Alzheimer's disease in
      PubMed, Cochrane Library, and four major Chinese electronic databases from their
      inception to June 2013. We performed meta-analyses using RevMan 5.1 software.
      (Protocol ID: CRD42012003249). RESULTS: 20 RCTs including 1823 participants were
      included. The methodological quality of most included trials had a high risk of
      bias. Compared with placebo, Huperzine A showed a significant beneficial effect
      on the improvement of cognitive function as measured by Mini-Mental State
      Examination (MMSE) at 8 weeks, 12 weeks and 16 weeks, and by Hastgawa Dementia
      Scale (HDS) and Wechsler Memory Scale (WMS) at 8 weeks and 12 weeks. Activities
      of daily living favored Huperzine A as measured by Activities of Daily Living
      Scale (ADL) at 6 weeks, 12 weeks and 16 weeks. One trial found Huperzine A
      improved global clinical assessment as measured by Clinical Dementia Rating Scale
      (CDR). One trial demonstrated no significant change in cognitive function as
      measured by Alzheimer's disease Assessment Scale-Cognitive Subscale (ADAS-Cog)
      and activity of daily living as measured by Alzheimer's disease Cooperative Study
      Activities of Daily Living Inventory (ADCS-ADL) in Huperzine A group. Trials
      comparing Huperzine A with no treatment, psychotherapy and conventional medicine
      demonstrated similar findings. No trial evaluated quality of life. No trial
      reported severe adverse events of Huperzine A. CONCLUSIONS: Huperzine A appears
      to have beneficial effects on improvement of cognitive function, daily living
      activity, and global clinical assessment in participants with Alzheimer's
      disease. However, the findings should be interpreted with caution due to the poor
      methodological quality of the included trials.

PMID- 24086397
TI  - Sodium butyrate induces growth inhibition and apoptosis in human prostate cancer
      DU145 cells by up-regulation of the expression of annexin A1.
AB  - BACKGROUND: Sodium butyrate, a histone deacetylase inhibitor, has emerged as a
      promising anticancer drug for multiple cancers. Recent studies have indicated
      that sodium butyrate could inhibit the progression of prostate cancer; however,
      the exact mechanism is still unclear. The aim of this study was to investigate
      the mechanism of sodium butyrate action in prostate cancer DU145 cells. METHODS:
      The inhibitory effects of NaB on cell growth were detected by the 3-(4, 5
      dimethylthiazol-2-yl)-2, 5-diphenyltetrrazolium bromide assay. Cell apoptosis was
      determined by flow cytometric analysis of DU145 cells stained with annexin V and
      PI. Hoechst 33258 and fluorescence microscopes were used to observe the nuclear
      morphology of DU145 cells after treatment with NaB. ANXA1 knockdown cells were
      established through transfection with ANXA1 siRNA. ANXA1 mRNA levels were
      measured by qRT-PCR. Bcl-2, Bax, ANXA1, ERK1/2 and pERK1/2 were detected by
      western blot. RESULTS: NaB significantly inhibited the growth and induction
      apoptosis of DU145 and PC3 cells in a dose-dependent manner. Expression of the
      anti-apoptosis gene Bcl-xl and Bcl-2 in DU145 cells are decreased and expression
      of the pro-apoptosis gene Bax and Bak increased after NaB treatment. Further
      studies have demonstrated that NaB up-regulated the expression of ANXA1 and that
      the tumor inhibition action of NaB was reduced markedly through knockdown of the
      ANXA1 gene in DU145 cells. Moreover, the siANXA1 cells showed that cell
      proliferation increased and cell apoptosis was induced by the inactivation of
      extracellular regulated kinase (ERK). CONCLUSION: Our results support a
      significant correlation between NaB functions and ANXA1 expression in prostate
      cancer, and pave the way for further studying the molecular mechanism of NaB
      actions in cancers.

PMID- 24086398
TI  - FHOD1, a formin upregulated in epithelial-mesenchymal transition, participates in
      cancer cell migration and invasion.
AB  - Cancer cells can obtain their ability to invade and metastasise by undergoing
      epithelial-to-mesenchymal transition (EMT). Exploiting this mechanism of cellular
      plasticity, malignant cells can remodel their actin cytoskeleton and down
      regulate proteins needed for cell-cell contacts. The mechanisms of cytoskeletal
      reorganisation resulting in mesenchymal morphology and increased invasive
      potential are poorly understood. Actin nucleating formins have been implicated as
      key players in EMT. Here, we analysed which formins are altered in squamous cell
      carcinoma related EMT. FHOD1, a poorly studied formin, appeared to be markedly
      upregulated upon EMT. In human tissues FHOD1 was primarily expressed in
      mesenchymal cells, with little expression in epithelia. However, specimens from
      oral squamous cell cancers demonstrated consistent FHOD1 upregulation in
      mesenchymally transformed cells at the invasive edge. This upregulation was
      confirmed in an oral squamous carcinoma model, where FHOD1 expression was
      markedly increased upon EMT in a PI3K signalling dependent manner. In the EMT
      cells FHOD1 contributed to the spindle-shaped morphology and mesenchymal F-actin
      organization. Furthermore, functional assays demonstrated that FHOD1 contributes
      to cell migration and invasion. Finally, FHOD1 depletion reduced the ability of
      EMT cancer cells to form invadopodia and to degrade extracellular matrix. Our
      results indicate that FHOD1 participates in cytoskeletal changes in EMT. In
      addition, we show that FHOD1 upregulation occurs during cancer cell EMT in vivo,
      which indicates that FHOD1 may contribute to tumour progression. 

PMID- 24086399
TI  - Evaluation of new tools for malaria vector control in Cameroon: focus on long
      lasting insecticidal nets.
AB  - BACKGROUND: From 2006 to 2011, biological activity of insecticides for Indoor
      Residual Spraying (IRS), conventional treatment of nets (CTNs) or long lasting
      insecticidal nets (LLINs) was evaluated before their approval in Cameroon. The
      objective of the study was to select the best tools for universal malaria vector
      control coverage. METHODOLOGY: Bioassays were performed using WHO cones and the
      Kisumu susceptible strain of Anopheles gambiae s.s.. Among tested products,
      residual activity and wash resistance of Alpha-cypermethrin LLINs (Interceptor)
      and CTNs (Fendona) were assessed during 5 months in the Ntougou neighborhood.
      PRINCIPAL FINDINGS: All the 14 tested products were found effective (95-100%
      knockdown and mortality rates), although a significant decrease of efficacy was
      seen with lambda-cyhalothrinWP IRS, alpha-cypermethrin CTNs and LLINs (p< 0.05).
      However, the efficacy of Interceptor nets did not decrease during the 5 months
      evaluation, even after 25 washes (0.07<p< 0.9). Meanwhile Fendona SC nets
      displayed a drastic decrease of activity after 5 washes, odds ratio was 3.07 (1.0
      8.59). CONCLUSION: This study provided useful data for decision making and
      community education toward universal coverage of malaria vector control in
      Cameroon.

PMID- 24086400
TI  - Spatiotemporal molecular analysis of cyanobacteria blooms reveals Microcystis-
      Aphanizomenon interactions.
AB  - Spatial and temporal variability in cyanobacterial community composition (CCC)
      within and between eutrophic lakes is not well-described using culture
      independent molecular methods. We analyzed CCC across twelve locations in four
      eutrophic lakes and within-lake locations in the Yahara Watershed, WI, on a
      weekly basis, for 5 months. Taxa were discriminated by length of MspI-digested
      cpcB/A intergenic spacer gene sequences and identified by comparison to a PCR
      based clone library. CCC across all stations was spatially segregated by depth of
      sampling locations (ANOSIM R = 0.23, p < 0.001). Accordingly, CCC was correlated
      with thermal stratification, nitrate and soluble reactive phosphorus (SRP, R =
      0.2-0.3). Spatial variability in CCC and temporal trends in taxa abundances were
      rarely correlative between sampling locations in the same lake indicating
      significant within lake spatiotemporal heterogeneity. Across all stations, a
      total of 37 bloom events were observed based on distinct increases in
      phycocyanin. Out of 97 taxa, a single Microcystis, and two different
      Aphanizomenon taxa were the dominant cyanobacteria detected during bloom events.
      The Microcystis and Aphanizomenon taxa rarely bloomed together and were
      significantly anti-correlated with each other at 9 of 12 stations with Pearson R
      values of -0.6 to -0.9 (p < 0.001). Of all environmental variables measured,
      nutrients, especially nitrate were significantly greater during periods of
      Aphanizomenon dominance while the nitrate+nitrite:SRP ratio was lower. This study
      shows significant spatial variability in CCC within and between lakes structured
      by depth of the sampling location. Furthermore, our study reveals specific
      genotypes involved in bloom formation. More in-depth characterization of these
      genotypes should lead to a better understanding of factors promoting bloom events
      in these lakes and more reliable bloom prediction models. 

PMID- 24086401
TI  - beta2 adrenergic receptor fluorescent protein fusions traffic to the plasma
      membrane and retain functionality.
AB  - Green fluorescent protein (GFP) has proven useful for the study of protein
      interactions and dynamics for the last twenty years. A variety of new fluorescent
      proteins have been developed that expand the use of available excitation spectra.
      We have undertaken an analysis of seven of the most useful fluorescent proteins
      (XFPs), Cerulean (and mCerulean3), Teal, GFP, Venus, mCherry and TagRFP657, as
      fusions to the archetypal G-protein coupled receptor, the beta2 adrenergic
      receptor (beta2AR). We have characterized these beta2AR::XFP fusions in respect
      to membrane trafficking and G-protein activation. We noticed that in the mouse
      neural cell line, OP 6, that membrane bound beta2AR::XFP fusions robustly
      localized in the filopodia identical to gap::XFP fusions. All beta2AR::XFP
      fusions show responses indistinguishable from each other and the non-fused form
      after isoprenaline exposure. Our results provide a platform by which G-protein
      coupled receptors can be dissected for their functionality. 

PMID- 24086402
TI  - The nociceptin/orphanin FQ receptor antagonist UFP-101 reduces microvascular
      inflammation to lipopolysaccharide in vivo.
AB  - Microvascular inflammation occurs during sepsis and the endogenous opioid-like
      peptide nociceptin/orphanin FQ (N/OFQ) is known to regulate inflammation. This
      study aimed to determine the inflammatory role of N/OFQ and its receptor NOP
      (ORL1) within the microcirculation, along with anti-inflammatory effects of the
      NOP antagonist UFP-101 (University of Ferrara Peptide-101) in an animal model of
      sepsis (endotoxemia). Male Wistar rats (220 to 300 g) were administered
      lipopolysaccharide (LPS) for 24 h (-24 h, 1 mg kg(-1); -2 h, 1 mg kg(-1) i.v.,
      tail vein). They were then either anesthetised for observation of the mesenteric
      microcirculation using fluorescent in vivo microscopy, or isolated arterioles
      (~200 um) were studied in vitro with pressure myography. 200 nM kg(-1)
      fluorescently labelled N/OFQ (FITC-N/OFQ, i.a., mesenteric artery) bound to
      specific sites on the microvascular endothelium in vivo, indicating sparse
      distribution of NOP receptors. In vitro, arterioles (~200 um) dilated to
      intraluminal N/OFQ (10(-5)M) (32.6 + 8.4%) and this response was exaggerated with
      LPS (62.0 +7.9%, p=0.031). In vivo, LPS induced macromolecular leak of FITC-BSA
      (0.02 g kg(-1) i.v.) (LPS: 95.3 (86.7 to 97.9)%, p=0.043) from post-capillary
      venules (<40 um) and increased leukocyte rolling as endotoxemia progressed
      (p=0.027), both being reduced by 150 nmol kg(-1) UFP-101 (i.v., jugular vein).
      Firstly, the rat mesenteric microcirculation expresses NOP receptors and
      secondly, NOP function (ability to induce dilation) is enhanced with LPS. UFP-101
      also reduced microvascular inflammation to endotoxemia in vivo. Hence inhibition
      of the microvascular N/OFQ-NOP pathway may have therapeutic potential during
      sepsis and warrants further investigation. 

PMID- 24086404
TI  - Multiple genomic recombination events in the evolution of saffold cardiovirus.
AB  - BACKGROUND: Saffold cardiovirus (SAFV) is a new human cardiovirus with 11
      identified genotypes. Little is known about the natural history and pathogenicity
      of SAFVs. METHODOLOGY/PRINCIPAL FINDINGS: We sequenced the genome of five SAFV-1
      strains which were identified from fecal samples taken from children with viral
      diarrhea in Beijing, China between March 2006 and November 2007, and analyzed the
      phylogenetic and phylodynamic properties of SAFVs using the genome sequences of
      every known SAFV genotypes. We identified multiple recombination events in our
      SAFV-1 strains, specifically recombination between SAFV-2, -3, -4, -9, -10 and
      the prototype SAFV-1 strain in the VP4 region and recombination between SAFV-4, 
      6, -8, -10, -11 and prototype SAFV-1 in the VP1/2A region. Notably, recombination
      in the structural gene VP4 is a rare event in Cardiovirus. The ratio of
      nonsynonymous substitutions to synonymous substitutions indicates a purifying
      selection of the SAFV genome. Phylogenetic and molecular clock analysis indicates
      the existence of at least two subclades of SAFV-1 with different origins.
      Subclade 1 includes two strains isolated from Pakistan, whereas subclade 2
      includes the prototype strain and strains isolated in China, Pakistan, and
      Afghanistan. The most recent common ancestor of all SAFV genotypes dates to the
      1710s, and SAFV-1, -2, and -3 to the 1940s, 1950s, and 1960s, respectively. No
      obvious relationship between variation and pathogenicity exists in the critical
      domains of the CD and EF loops of viral capsid proteins or the multi-functional
      proteins L based on amino acid sequence identity comparison between SAFV
      genotypes. CONCLUSIONS/SIGNIFICANCE: Our findings suggest that intertypic
      recombination plays an important role in the diversity of SAFVs, highlighting the
      diversity of the five strains with the previously described SAFV-1 strains.

PMID- 24086403
TI  - Expression of Fragaria vesca PIP aquaporins in response to drought stress: PIP
      down-regulation correlates with the decline in substrate moisture content.
AB  - PIP aquaporin responses to drought stress can vary considerably depending on the
      isoform, tissue, species or level of stress; however, a general down-regulation
      of these genes is thought to help reduce water loss and prevent backflow of water
      to the drying soil. It has been suggested therefore, that it may be necessary for
      the plant to limit aquaporin production during drought stress, but it is unknown
      whether aquaporin down-regulation is gradual or triggered by a particular
      intensity of the stress. In this study, ten Fragaria PIP genes were identified
      from the woodland strawberry (Fragaria vesca L.) genome sequence and
      characterised at the sequence level. The water relations of F. vesca were
      investigated and the effect of different intensities of drought stress on the
      expression of four PIP genes, as well as how drought stress influences their
      diurnal transcription was determined. PIP down-regulation in the root
      corresponded to the level of drought stress. Moreover, transcript abundance of
      two genes highly expressed in the root (FvPIP1;1 and FvPIP2;1) was strongly
      correlated to the decline in substrate moisture content. The amplitude of diurnal
      aquaporin expression in the leaves was down-regulated by drought without altering
      the pattern, but showing an intensity-dependent effect. The results show that
      transcription of PIP aquaporins can be fine-tuned with the environment in
      response to declining water availability. 

PMID- 24086405
TI  - Usage of adenovirus expressing thymidine kinase mediated hepatocellular damage
      for enabling mouse liver repopulation with allogenic or xenogenic hepatocytes.
AB  - It has been shown that the liver of immunodeficient mice can be efficiently
      repopulated with human hepatocytes when subjected to chronic hepatocellular
      damage. Mice with such chimeric livers represent useful reagents for medical and
      clinical studies. However all previously reported models of humanized livers are
      difficult to implement as they involve cross-breeding of immunodeficient mice
      with mice exhibiting genetic alterations causing sustained hepatic injury. In
      this paper we attempted to create chimeric livers by inducing persistent
      hepatocellular damage in immunodeficient Rag2(-/-) gammac(-/-) mice using an
      adenovirus encoding herpes virus thymidine kinase (AdTk) and two consecutive
      doses of ganciclovir (GCV). We found that this treatment resulted in
      hepatocellular damage persisting for at least 10 weeks and enabled efficient
      engraftment and proliferation within the liver of either human or allogenic
      hepatocytes. Interestingly, while the nodules generated from the transplanted
      mouse hepatocytes were well vascularized, the human hepatocytes experienced
      progressive depolarization and exhibited reduced numbers of murine endothelial
      cells inside the nodules. In conclusion, AdTk/GCV-induced liver damage licenses
      the liver of immunodeficient mice for allogenic and xenogenic hepatocyte
      repopulation. This approach represents a simple alternative strategy for chimeric
      liver generation using immunodeficient mice without additional genetic
      manipulation of the germ line. 

PMID- 24086406
TI  - Flexibility of the programme of spore coat formation in Bacillus subtilis: bypass
      of CotE requirement by over-production of CotH.
AB  - Bacterial spores are surrounded by the coat, a multilayered shell that
      contributes in protecting the genome during stress conditions. In Bacillus
      subtilis, the model organism for spore formers, the coat is composed by about
      seventy different proteins, organized into four layers by the action of several
      regulatory proteins. A major component of this regulatory network, CotE, is
      needed to assemble the outer coat and develop spores fully resistant to lysozyme
      and able to germinate efficiently. Another regulator, CotH, is controlled by CotE
      and is present in low amounts both during sporulation and in mature spores. In
      spite of this CotH controls the assembly of at least nine outer coat proteins and
      cooperates with CotE in producing fully resistant and efficiently germinating
      spores. In order to improve our understanding of CotH role in spore formation, we
      over-produced CotH by placing its coding region under the control of a promoter
      stronger than its own promoter but with a similar timing of activity during
      sporulation. Over-production of CotH in an otherwise wild type strain did not
      cause any major effect, whereas in a cotE null background a partial recovery of
      the phenotypes associated to the cotE null mutation was observed. Western blot,
      fluorescence microscopy and Surface-Enhanced Raman Scattering spectroscopy data
      indicate that, in the absence of CotE, over-production of CotH allowed the
      formation of spores overall resembling wild type spores and carrying in their
      coat some CotE-/CotH-dependant proteins. Our results suggest that the B. subtilis
      spore differentiation programme is flexible, and that an increase in the amount
      of a regulatory protein can replace a missing partner and partially substitute
      its function in the assembly of the spore coat. 

PMID- 24086408
TI  - Adolescent health and high school dropout: a prospective cohort study of 9000
      Norwegian adolescents (the Young-HUNT).
AB  - BACKGROUND: High school dropout is of major concern in the western world. Our
      aims were to estimate the risk of school dropout in adolescents following chronic
      somatic disease, somatic symptoms, psychological distress, concentration
      difficulties, insomnia or overweight and to assess to which extent the family
      contributes to the association between health and school dropout. METHODS: A
      population of 8950 school-attending adolescents (13-21 years) rated their health
      in the Young-HUNT 1 Study (90% response rate) in 1995-1997. High school dropout
      or completion, was defined with the Norwegian National Education Database in the
      calendar year the participant turned 24 years old. Parental socioeconomic status
      was defined by using linkages to the National Education Database, the National
      Insurance Administration and the HUNT2 Survey. We used logistic regression to
      estimate odds ratios and risk differences of high school dropout, both in the
      whole population and among siblings within families differentially exposed to
      health problems. RESULTS: All explored health dimensions were strongly associated
      with high school dropout. In models adjusted for parental socioeconomic status,
      the risk differences of school dropout according to health exposures varied
      between 3.6% (95% CI 1.7 to 5.5) for having >= 1 somatic disease versus none and
      11.7% (6.3 to 17.0) for being obese versus normal weight. The results from the
      analyses comparing differentially exposed siblings, confirmed these results with
      the exception of weaker associations for somatic diseases and psychological
      distress. School dropout was strongly clustered within families (family level
      conditional intraclass correlation 0.42). CONCLUSIONS: Adolescent health problems
      are markers for high school dropout, independent of parental socioeconomic
      status. Although school dropout it strongly related to family-level factors, also
      siblings with poor health have reduced opportunity to complete high school
      compared to healthy siblings. Public health policy should focus on ensuring young
      people with poor health the best attainable education.

PMID- 24086407
TI  - Aryl hydrocarbon receptor-dependent retention of nuclear HuR suppresses cigarette
      smoke-induced cyclooxygenase-2 expression independent of DNA-binding.
AB  - The aryl hydrocarbon receptor (AhR), a ligand-activated transcription factor that
      responds to man-made environmental toxicants, has emerged as an endogenous
      regulator of cyclooxygenase-2 (Cox-2) by a mechanism that is poorly understood.
      In this study, we first used AhR-deficient (AhR(-/-) ) primary pulmonary cells,
      together with pharmacological tools to inhibit new RNA synthesis, to show that
      the AhR is a prominent factor in the destabilization of Cox-2 mRNA. The
      destabilization of Cox-2 mRNA and subsequent suppression of cigarette smoke
      induced COX-2 protein expression by the AhR was independent of its ability to
      bind the dioxin response element (DRE), thereby differentiating the DRE-driven
      toxicological AhR pathway from its anti-inflammatory abilities. We further
      describe that the AhR destabilizes Cox-2 mRNA by sequestering HuR within the
      nucleus. The role of HuR in AhR stabilization of Cox-2 mRNA was confirmed by
      knockdown of HuR, which resulted in rapid Cox-2 mRNA degradation. Finally, in the
      lungs of AhR(-/-) mice exposed to cigarette smoke, there was little Cox-2 mRNA
      despite robust COX-2 protein expression, a finding that correlates with almost
      exclusive cytoplasmic HuR within the lungs of AhR(-/-) mice. Therefore, we
      propose that the AhR plays an important role in suppressing the expression of
      inflammatory proteins, a function that extends beyond the ability of the AhR to
      respond to man-made toxicants. These findings open the possibility that a DRE
      independent AhR pathway may be exploited therapeutically as an anti-inflammatory
      target. 

PMID- 24086409
TI  - Medial prefrontal cortex activation is commonly invoked by reputation of self and
      romantic partners.
AB  - The reputation of others influences partner selection in human cooperative
      behaviors through verbal reputation representation. Although the way in which
      humans represent the verbal reputations of others is a pivotal issue for social
      neuroscience, the neural correlates underlying the representation of verbal
      reputations of others are unclear. Humans primarily depend on self-evaluation
      when assessing reputation of self. Likewise, humans might primarily depend on
      self-evaluation of others when representing their reputation. As interaction
      promotes the formation of more nuanced, individualized impressions of an
      interaction partner, humans tend to form self-evaluations of persons with whom
      they are intimate in their daily life. Thus, we hypothesized that the
      representation of reputation of others is modulated by intimacy due to one's own
      evaluation formation of that person. To test this hypothesis, we conducted a
      functional magnetic resonance imaging experiment with 11 pairs of romantic
      partners while they viewed an evaluation of a target person (self, partner
      [intimate other], or stranger [non-intimate other]), made by other evaluators.
      When compared with strangers, viewing evaluations of self and partner activated
      overlapping regions in the medial prefrontal cortex. Verbal reputation of self
      specific activation was found in the precuneus, which represents self-related
      processing. The data suggest that midline structures represent reputation of
      self. In addition, intimacy-modulated activation in the medial prefrontal cortex
      suggests that the verbal reputation of intimate others is represented similarly
      to reputation of self. These results suggest that the reputation representation
      in the medial prefrontal cortex is engaged by verbal reputation of self and
      intimate others stemming from both own and other evaluators' judgments. 

PMID- 24086410
TI  - Personal space regulation in childhood autism spectrum disorders.
AB  - People appropriately adjust the distance between themselves and others during
      social interaction, and they may feel discomfort and move away when another
      person intrudes on their personal space. In the present study, we investigated
      personal space in children with persistent difficulties in the domain of social
      behavior, such as children with autism spectrum disorders (ASD), and in children
      with typical development (TD). The stop-distance paradigm was used to derive
      estimates of interpersonal distance, before and after a brief interaction with an
      unfamiliar adult confederate. The results showed that ASD children felt
      comfortable at a greater distance compared to TD children. Moreover, personal
      space shrunk after interaction with the confederate in TD children, but it failed
      to do so in ASD children. These findings reveal that autism deeply affects the
      regulation of personal space, influencing both its size and flexibility. 

PMID- 24086411
TI  - Preconditioning with triiodothyronine improves the clinical signs and acute
      tubular necrosis induced by ischemia/reperfusion in rats.
AB  - BACKGROUND: Renal ischemia/reperfusion (I/R) injury is manifested by acute renal
      failure (ARF) and acute tubular necrosis (ATN). The aim of this study was to
      evaluate the effectiveness of preconditioning with 3, 3, 5 triiodothyronine (T3)
      to prevent I/R renal injury. METHODOLOGY/PRINCIPAL FINDINGS: The rats were
      divided into four groups: sham-operated, placebo-treated (SO-P), sham-operated T3
      treated (SO- T3), I/R-injured placebo-treated (IR-P), and I/R-injured T3-treated
      (IR- T3) groups. At 24 h before ischemia, the animals received a single dose of
      T3 (100 MUg/kg). Renal function and plasma, urinary, and tissue variables were
      studied at 4, 24, and 48 h of reperfusion, including biochemical, oxidative
      stress, and inflammation variables, PARP-1 immunohistochemical expression, and
      ATN morphology. In comparison to the SO groups, the IR-P groups had higher plasma
      urea and creatinine levels and greater proteinuria (at all reperfusion times) and
      also showed: increased oxidative stress-related plasma, urinary, and tissue
      variables; higher plasma levels of IL6 (proinflammatory cytokine); increased
      glomerular and tubular nuclear PARP-1 expression; and a greater degree of ATN.
      The IR-T3 group showed a marked reduction in all of these variables, especially
      at 48 h of reperfusion. No significant differences were observed between SO-P and
      SO-T3 groups. CONCLUSIONS: This study demonstrates that preconditioning rats with
      a single dose of T3 improves the clinical signs and ATN of renal I/R injury.
      These beneficial effects are accompanied by reductions in oxidative stress,
      inflammation, and renal PARP-1 expression, indicating that this sequence of
      factors plays an important role in the ATN induced by I/R injury.

PMID- 24086412
TI  - Comparing same day sputum microscopy with conventional sputum microscopy for the
      diagnosis of tuberculosis--Chhattisgarh, India.
AB  - BACKGROUND: The World Health Organization (WHO) recommends same day sputum
      microscopy (spot-spot) in preference to conventional strategy (spot-morning) for
      the diagnosis of smear positive tuberculosis with the view that completing
      diagnosis on a single day may be more convenient to the patients and reduce pre
      treatment losses to follow-up. METHODS: We conducted a cross-sectional study in
      seven selected district level hospitals of Chhattisgarh State, India. During
      October 2012 - March 2013, two sputum specimens (spot-early morning) were
      collected from consecutively enrolled adult (>= 18 years) presumptive TB patients
      as per current national guidelines. In addition, a second sample was collected
      (one hour after the collection of first spot sample) from the same patients. All
      the samples were examined by ziehl-Neelsen (ZN) microscopy. McNemar's test was
      used to compare statistical differences in the proportion smear positive between
      the two approaches (spot-spot versus spot-morning). RESULTS: Of 2551 presumptive
      TB patients, 69% were male. All patients provided the first spot specimen, 2361
      (93%) provided the second spot specimen, and 2435 (96%) provided an early morning
      specimen. 72% of specimens were mucopurulent in conventional strategy as compared
      to 60% in same day strategy. The proportion of smear-positive patients diagnosed
      by same day microscopy was 14%, as compared to 17% by the conventional method
      (p<0.001). A total of 73 (16.9%) potential cases were missed by the same day
      method compared to only 2 (0.5%) by the conventional method. CONCLUSION: Same-day
      microscopy method missed 17% of smear-positive cases and contrary to prior
      perception, did not increase the proportion of suspects providing the second
      sample. These findings call for an urgent need to revisit the WHO recommendation
      of switching to same-day diagnosis over the current policy.

PMID- 24086413
TI  - Spontaneous usage of different shortcuts based on the commutativity principle.
AB  - Based on research on expertise a person can be said to possess integrated
      conceptual knowledge when she/he is able to spontaneously identify task relevant
      information in order to solve a problem efficiently. Despite the lack of
      instruction or explicit cueing, the person should be able to recognize which
      shortcut strategy can be applied--even when the task context differs from the one
      in which procedural knowledge about the shortcut was originally acquired. For
      mental arithmetic, first signs of such adaptive flexibility should develop
      already in primary school. The current study introduces a paper-and-pencil-based
      as well as an eyetracking-based approach to unobtrusively measure how students
      spot and apply (known) shortcut options in mental arithmetic. We investigated the
      development and the relation of the spontaneous use of two strategies derived
      from the mathematical concept of commutativity. Children from grade 2 to grade 7
      and university students solved three-addends addition problems, which are rarely
      used in class. Some problems allowed the use of either of two commutativity-based
      shortcut strategies. Results suggest that from grade three onwards both of the
      shortcuts were used spontaneously and application of one shortcut correlated
      positively with application of the other. Rate of spontaneous usage was
      substantial but smaller than in an instructed variant. Eyetracking data suggested
      similar fixation patterns for spontaneous an instructed shortcut application. The
      data are consistent with the development of an integrated concept of the
      mathematical principle so that it can be spontaneously applied in different
      contexts and strategies.

PMID- 24086414
TI  - A metagenomics transect into the deepest point of the Baltic Sea reveals clear
      stratification of microbial functional capacities.
AB  - The Baltic Sea is characterized by hyposaline surface waters, hypoxic and anoxic
      deep waters and sediments. These conditions, which in turn lead to a steep oxygen
      gradient, are particularly evident at Landsort Deep in the Baltic Proper. Given
      these substantial differences in environmental parameters at Landsort Deep, we
      performed a metagenomic census spanning surface to sediment to establish whether
      the microbial communities at this site are as stratified as the physical
      environment. We report strong stratification across a depth transect for both
      functional capacity and taxonomic affiliation, with functional capacity
      corresponding most closely to key environmental parameters of oxygen, salinity
      and temperature. We report similarities in functional capacity between the
      hypoxic community and hadal zone communities, underscoring the substantial degree
      of eutrophication in the Baltic Proper. Reconstruction of the nitrogen cycle at
      Landsort deep shows potential for syntrophy between archaeal ammonium oxidizers
      and bacterial denitrification at anoxic depths, while anaerobic ammonium
      oxidation genes are absent, despite substantial ammonium levels below the
      chemocline. Our census also reveals enrichment in genetic prerequisites for a
      copiotrophic lifestyle and resistance mechanisms reflecting adaptation to
      prevalent eutrophic conditions and the accumulation of environmental pollutants
      resulting from ongoing anthropogenic pressures in the Baltic Sea. 

PMID- 24086415
TI  - Gender and timing during ontogeny matter: effects of a temporary high temperature
      on survival, body size and colouration in Harmonia axyridis.
AB  - The ambient temperature experienced during development is a crucial factor
      affecting survival and adult phenotype in ectotherms. Moreover, the exact
      response of individuals to different temperature regimes is frequently sex
      specific. This sex-specific response can result in varying levels of sexual
      dimorphism according to the experienced conditions. The majority of studies have
      investigated the effects of temperature on individuals reared under a constant
      temperature regime throughout their whole preimaginal development, whereas
      information on stage-dependent variation in temperature effects is scarce. Here
      we investigate how the stage at which elevated temperature is experienced
      influences survival, adult body size and colouration in the harlequin ladybird
      Harmonia axyridis form succinea. The effects of timing of exposure to elevated
      temperature on the adult phenotype are assessed separately for males and females.
      Control individuals were reared at a constant temperature of 20  degrees C.
      Beetles in other treatments were additionally exposed to 33  degrees C for 48
      hours during the following developmental stages: egg, 1(st) to 2(nd) larval
      instar, 3(rd) larval instar, 4(th) larval instar and pupa. Exposure to an
      elevated temperature during the early developmental stages resulted in lower
      survival, but the adult phenotype of survivors was almost unaffected. Exposure to
      an elevated temperature during the later developmental stages (4(th) larval
      instar or pupa) resulted in the decreased melanisation of elytra, decreased
      structural body size and increased dry mass. Furthermore, the timing of high
      temperature exposure affected the degree of sexual dimorphism in elytral
      melanisation and dry mass. We demonstrate that the effects of elevated
      temperature can vary according to the developmental stage at exposure. Detailed
      information on how ambient temperature affects the developmental biology of
      ectotherms is crucial for modeling population growth and predicting the spread of
      invasive species such as Harmonia axyridis.

PMID- 24086417
TI  - Listening to Limericks: a pupillometry investigation of perceivers' expectancy.
AB  - What features of a poem make it captivating, and which cognitive mechanisms are
      sensitive to these features? We addressed these questions experimentally by
      measuring pupillary responses of 40 participants who listened to a series of
      Limericks. The Limericks ended with either a semantic, syntactic, rhyme or metric
      violation. Compared to a control condition without violations, only the rhyme
      violation condition induced a reliable pupillary response. An anomaly-rating
      study on the same stimuli showed that all violations were reliably detectable
      relative to the control condition, but the anomaly induced by rhyme violations
      was perceived as most severe. Together, our data suggest that rhyme violations in
      Limericks may induce an emotional response beyond mere anomaly detection. 

PMID- 24086416
TI  - Prevalence and genetic characterization of Cryptosporidium in yaks in Qinghai
      Province of China.
AB  - The objective of this study was to determine the prevalence, species and subtypes
      of Cryptosporidium infecting yaks in the Qinghai Province of Northwestern China.
      The prevalence of Cryptosporidium spp. was detected by microscopy and nested-PCR.
      A total of 586 fecal samples were collected from yaks in 6 counties, of which 142
      (24.2%) samples tested positive for Cryptosporidium. The small subunit (SSU) rRNA
      gene of fifty-five samples were amplified and sequenced successfully and
      demonstrated that Cryptosporidium bovis (31/55, 56.4%) was the most common
      species, followed by C. parvum (16/55, 29.1%) and C. ryanae (5/55, 9.0%). Mixed
      infections of C. parvum and C. bovis (n = 2), C. ryanae and C. bovis (n = 1) were
      also detected. All three species were found in yaks ranging in age from <1 year,
      1-2 years, to >2 years. Cryptosporidium was most commonly detected in spring
      (28.4%), followed by summer (20.9%), then winter (17.5%). Cryptosporidium parvum
      positive samples were subtyped using the 60 kDa glycoprotein (gp60) gene.
      Subtypes IIaA15G2R1 (n = 8), IIaA16G2R1 (n = 2), IIaA14G1R1 (n = 1), IIaA14G2R1
      (n = 1) and IIaA16G3R1 (n = 1) were detected. All of these subtypes are zoonotic,
      and may pose a potential threat to human health.

PMID- 24086418
TI  - Genomic insights into triple-negative and HER2-positive breast cancers using
      isogenic model systems.
AB  - INTRODUCTION: In general, genomic signatures of breast cancer subtypes have
      little or no overlap owing to the heterogeneous genetic backgrounds of study
      samples. Thus, obtaining a reliable signature in the context of isogenic nature
      of the cells has been challenging and the precise contribution of isogenic triple
      negative breast cancer (TNBC) versus non-TNBC remains poorly defined. METHODS: We
      established isogenic stable cell lines representing TNBC and Human Epidermal
      Growth Factor Receptor 2 positive (HER2+) breast cancers by introducing HER2 in
      TNBC cell lines MDA-MB-231 and MDA-MB-468. We examined protein level expression
      and functionality of the transfected receptor by treatment with an antagonist of
      HER2. Using microarray profiling, we obtained a comprehensive gene list of
      differentially expressed between TNBC and HER2+ clones. We identified and
      validated underlying isogenic components using qPCR and also compared results
      with expression data from patients with similar breast cancer subtypes. RESULTS:
      We identified 544 and 1087 statistically significant differentially expressed
      genes between isogenic TNBC and HER2+ samples in MDA-MB-231 and MDA-MB-468
      backgrounds respectively and a shared signature of 49 genes. By comparing results
      from MDA-MB-231 and MDA-MB-468 backgrounds with two patient microarray datasets,
      we identified 17 and 22 common genes with same expression trend respectively.
      Additionally, we identified 56 and 78 genes from MDA-MB-231 and MDA-MB-468
      comparisons respectively present in our published RNA-seq data. CONCLUSIONS:
      Using our unique model system, we have identified an isogenic gene expression
      signature between TNBC and HER2+ breast cancer. A portion of our results was also
      verified in patient data samples, indicating an existence of isogenic element
      associated with HER2 status between genetically heterogeneous breast cancer
      samples. These findings may potentially contribute to the development of
      molecular platform that would be valuable for diagnostic and therapeutic decision
      for TNBC and in distinguishing it from HER2+ subtype.

PMID- 24086420
TI  - Reconstruction of the drive underlying food intake and its control by leptin and
      dieting.
AB  - The intake of food and the expenditure of calories is modelled by a system of
      differential equations. The state variables are the amount of calories stored in
      adipose tissue and the level of plasma leptin. The model has as input a drive
      that controls the intake of food. This drive consists of a collective of
      physiological and psychological incentives to eat or to stop eating. An
      individual based approach is presented by which the parameters of the system can
      be set using data of a subject. The method of analysis is fully worked out using
      weight data of two persons. The model is prone to extensions by transferring
      incentives being part of the input to the collection of state variables. 

PMID- 24086419
TI  - Analysis of the Ush2a gene in medaka fish (Oryzias latipes).
AB  - Patients suffering from Usher syndrome (USH) exhibit sensorineural hearing loss,
      retinitis pigmentosa (RP) and, in some cases, vestibular dysfunction. USH is the
      most common genetic disorder affecting hearing and vision and is included in a
      group of hereditary pathologies associated with defects in ciliary function known
      as ciliopathies. This syndrome is clinically classified into three types: USH1,
      USH2 and USH3. USH2 accounts for well over one-half of all Usher cases and
      mutations in the USH2A gene are responsible for the majority of USH2 cases, but
      also for atypical Usher syndrome and recessive non-syndromic RP. Because medaka
      fish (Oryzias latypes) is an attractive model organism for genetic-based studies
      in biomedical research, we investigated the expression and function of the USH2A
      ortholog in this teleost species. Ol-Ush2a encodes a protein of 5.445 aa codons,
      containing the same motif arrangement as the human USH2A. Ol-Ush2a is expressed
      during early stages of medaka fish development and persists into adulthood.
      Temporal Ol-Ush2a expression analysis using whole mount in situ hybridization
      (WMISH) on embryos at different embryonic stages showed restricted expression to
      otoliths and retina, suggesting that Ol-Ush2a might play a conserved role in the
      development and/or maintenance of retinal photoreceptors and cochlear hair cells.
      Knockdown of Ol-Ush2a in medaka fish caused embryonic developmental defects
      (small eyes and heads, otolith malformations and shortened bodies with curved
      tails) resulting in late embryo lethality. These embryonic defects, observed in
      our study and in other ciliary disorders, are associated with defective cell
      movement specifically implicated in left-right (LR) axis determination and planar
      cell polarity (PCP). 

PMID- 24086421
TI  - Semantic size of abstract concepts: it gets emotional when you can't see it.
AB  - Size is an important visuo-spatial characteristic of the physical world. In
      language processing, previous research has demonstrated a processing advantage
      for words denoting semantically "big" (e.g., jungle) versus "small" (e.g.,
      needle) concrete objects. We investigated whether semantic size plays a role in
      the recognition of words expressing abstract concepts (e.g., truth). Semantically
      "big" and "small" concrete and abstract words were presented in a lexical
      decision task. Responses to "big" words, regardless of their concreteness, were
      faster than those to "small" words. Critically, we explored the relationship
      between semantic size and affective characteristics of words as well as their
      influence on lexical access. Although a word's semantic size was correlated with
      its emotional arousal, the temporal locus of arousal effects may depend on the
      level of concreteness. That is, arousal seemed to have an earlier (lexical)
      effect on abstract words, but a later (post-lexical) effect on concrete words.
      Our findings provide novel insights into the semantic representations of size in
      abstract concepts and highlight that affective attributes of words may not always
      index lexical access. 

PMID- 24086422
TI  - Fine particulate matter and incident cognitive impairment in the REasons for
      Geographic and Racial Differences in Stroke (REGARDS) cohort.
AB  - Studies of the effect of air pollution on cognitive health are often limited to
      populations living near cities that have air monitoring stations. Little is known
      about whether the estimates from such studies can be generalized to the U.S.
      population, or whether the relationship differs between urban and rural areas. To
      address these questions, we used a satellite-derived estimate of fine particulate
      matter (PM2.5) concentration to determine whether PM2.5 was associated with
      incident cognitive impairment in a geographically diverse, biracial US cohort of
      men and women (n = 20,150). A 1-year mean baseline PM2.5 concentration was
      estimated for each participant, and cognitive status at the most recent follow-up
      was assessed over the telephone using the Six-Item Screener (SIS) in a subsample
      that was cognitively intact at baseline. Logistic regression was used to
      determine whether PM2.5 was related to the odds of incident cognitive impairment.
      A 10 ug/m(3) increase in PM2.5 concentration was not reliably associated with an
      increased odds of incident impairment, after adjusting for temperature, season,
      incident stroke, and length of follow-up [OR (95% CI): 1.26 (0.97, 1.64)]. The
      odds ratio was attenuated towards 1 after adding demographic covariates,
      behavioral factors, and known comorbidities of cognitive impairment. A 10 ug/m(3)
      increase in PM2.5 concentration was slightly associated with incident impairment
      in urban areas (1.40 [1.06-1.85]), but this relationship was also attenuated
      after including additional covariates in the model. Evidence is lacking that the
      effect of PM2.5 on incident cognitive impairment is robust in a heterogeneous US
      cohort, even in urban areas.

PMID- 24086423
TI  - Somatic overgrowth predisposes to seizures in autism spectrum disorders.
AB  - BACKGROUND: Comorbidity of Autism Spectrum Disorders with seizures or abnormal
      EEG (Autism-Epilepsy Phenotype) suggests shared pathomechanisms, and might be a
      starting point to identify distinct populations within the clinical complexity of
      the autistic spectrum. In this study, we tried to assess whether distinct
      subgroups, having distinctive clinical hallmarks, emerge from this comorbid
      condition. METHODS: Two-hundred and six individuals with idiopathic Autism
      Spectrum Disorders were subgrouped into three experimental classes depending on
      the presence of seizures and EEG abnormalities. Neurobehavioral, electroclinical
      and auxological parameters were investigated to identify differences among groups
      and features which increase the risk of seizures. Our statistical analyses used
      ANOVA, post-hoc multiple comparisons, and the Chi-squared test to analyze
      continuous and categorical variables. A correspondence analysis was also used to
      decompose significant Chi-squared and reduce variables dimensions. RESULTS: The
      high percentage of children with seizures (28.2% of our whole cohort) and EEG
      abnormalities (64.1%) confirmed that the prevalence of epilepsy in Autism
      Spectrum Disorders exceeds that of the general population. Seizures were
      associated with severe intellectual disability, and not with autism severity.
      Interestingly, tall stature (without macrocephaly) was significantly associated
      with EEG abnormalities or later onset seizures. However, isolated macrocephaly
      was equally distributed among groups or associated with early onset seizures when
      accompanied by tall stature. CONCLUSIONS: Tall stature seems to be a phenotypic
      "biomarker" of susceptibility to EEG abnormalities or late epilepsy in Autism
      Spectrum Disorders and, when concurring with macrocephaly, predisposes to early
      onset seizures. Growth pattern might act as an endophenotypic marker in Autism
      Epilepsy comorbidity, delineating distinct pathophysiological subtypes and
      addressing personalized diagnostic work-up and therapeutic approaches.

PMID- 24086424
TI  - The BTB-containing protein Kctd15 is SUMOylated in vivo.
AB  - Potassium Channel Tetramerization Domain containing 15 (Kctd15) has a role in
      regulating the neural crest (NC) domain in the embryo. Kctd15 inhibits NC
      induction by antagonizing Wnt signaling and by interaction with the transcription
      factor AP-2alpha activation domain blocking its activity. Here we demonstrate
      that Kctd15 is SUMOylated by SUMO1 and SUMO2/3. Kctd15 contains a classical SUMO
      interacting motif, psiKxE, at the C-terminal end, and variants of the motif
      within the molecule. Kctd15 SUMOylation occurs exclusively in the C-terminal
      motif. Inability to be SUMOylated did not affect Kctd15's subcellular
      localization, or its ability to repress AP-2 transcriptional activity and to
      inhibit NC formation in zebrafish embryos. In contrast, a fusion of Kctd15 and
      SUMO had little effectiveness in AP-2 inhibition and in blocking of NC formation.
      These data suggest that the non-SUMOylated form of Kctd15 functions in NC
      development. 

PMID- 24086425
TI  - Evaluation of bacterial expansin EXLX1 as a cellulase synergist for the
      saccharification of lignocellulosic Agro-industrial wastes.
AB  - Various types of lignocellulosic wastes extensively used in biofuel production
      were provided to assess the potential of EXLX1 as a cellulase synergist.
      Enzymatic hydrolysis of natural wheat straw showed that all the treatments using
      mixtures of cellulase and an optimized amount of EXLX1, released greater
      quantities of sugars than those using cellulase alone, regardless of cellulase
      dosage and incubation time. EXLX1 exhibited different synergism and binding
      characteristics for different wastes, but this can be related to their
      lignocellulosic components. The cellulose proportion could be one of the
      important factors. However, when the cellulose proportion of different biomass
      samples exhibited no remarkable differences, a higher synergism of EXLX1 is prone
      to occur on these materials, with a high proportion of hemicellulose and a low
      proportion of lignin. The information could be favorable to assess whether EXLX1
      is effective as a cellulase synergist for the hydrolysis of the used materials.
      Binding assay experiments further suggested that EXLX1 bound preferentially to
      alkali pretreated materials, as opposed to acid pretreated materials under the
      assay condition and the binding preference would be affected by incubation
      temperature. 

PMID- 24086426
TI  - Priority areas for large mammal conservation in Equatorial Guinea.
AB  - Hunting is one of the main driving forces behind large mammal density
      distribution in many regions of the world. In tropical Africa, urban demand for
      bushmeat has been shown to dominate over subsistence hunting and its impact often
      overrides spatial-ecological species characteristics. To effectively protect
      remaining mammal populations the main factors that influence their distribution
      need to be integrated into conservation area prioritisation and management plans.
      This information has been lacking for Rio Muni, Equatorial Guinea, as prior
      studies have been outdated or have not systematically covered the continental
      region of the country. In this study we evaluated: 1) the relative importance of
      local vs. commercial hunting; 2) wildlife density of protected vs. non-protected
      areas; and 3) the importance of ecological factors vs. human influence in driving
      mammal density distribution in Rio Muni. We adopted a systematic countrywide line
      transect approach with particular focus on apes and elephants, but also including
      other mammal species. For analysis of field data we used generalised linear
      models with a set of predictor variables representing ecological conditions,
      anthropogenic pressure and protected areas. We estimate that there are currently
      884 (437-1,789) elephants and 11,097 (8,719-13,592) chimpanzees and gorillas
      remaining in Rio Muni. The results indicate strong hunting pressures on both
      local and commercial levels, with roads demonstrating a negative impact on
      elephants and overall mammal body mass. Protected areas played no role in
      determining any of the mammal species distributions and significant human hunting
      signs were found inside these protected areas, illustrating the lack of
      environmental law enforcement throughout the country. Rio Muni is currently under
      represented in conservation efforts in Western Equatorial Africa, and we
      recommend a focus on cross-boundary conservation, in particular in the Monte Alen
      Monts de Cristal and Rio Campo Ma'an conservation landscapes, where the highest
      densities and diversity of large mammals remain. 

PMID- 24086427
TI  - Biased safety reporting in blinded randomized clinical trials: meta-analysis of
      angiotensin receptor blocker trials.
AB  - BACKGROUND: Cough is listed as an adverse drug reaction (ADR) on the labels of
      angiotensin receptor blockers (ARB). However, a causal association with cough has
      also been reported for angiotensin converting enzyme inhibitors (ACEI), which
      have frequently been used as comparator drugs in the registration clinical trials
      of ARBs. This prompted us to examine the possible influence of using comparator
      drugs with well-known ADRs on the safety reporting of investigational drugs in
      blinded randomized clinical trials. METHODS AND FINDINGS: The double-blinded,
      randomized clinical trials with comparator drugs were identified in the Japanese
      dossiers for the new drug applications of ARBs. The risk ratios (RR) of reporting
      cough and headache in ARB arms were calculated for each ARB by comparing trials
      using ACEIs and trials using non-ACEIs, were then combined with a meta-analysis.
      23 trials with a total of 6643 patients were identified, consisting 6 trials
      using an ACEI comparator including 819 ARB patients and 17 trials using a non
      ACEI comparator including 5824 ARB patients. The combined RR of cough reporting
      was significantly elevated (20.77; 95% confidence interval [CI], 7.47 to 57.76),
      indicating more frequent reporting of cough in clinical trials using an ACEI
      comparator. In contrast, the combined RR of headache, a negative control, was
      insignificant (1.45; 95% CI, 0.34 to 6.22). CONCLUSION: The use of comparators
      with well-known ADRs in blinded randomized trials produces potential bias in the
      reporting frequency of ADRs for investigational drugs. The selection of
      appropriate comparator drugs should be critical in unbiased safety assessment in
      double-blinded, randomized clinical trials and thus have relevance in reviewing
      the safety results from a regulatory point of view.

PMID- 24086428
TI  - From genes to milk: genomic organization and epigenetic regulation of the mammary
      transcriptome.
AB  - Even in genomes lacking operons, a gene's position in the genome influences its
      potential for expression. The mechanisms by which adjacent genes are co-expressed
      are still not completely understood. Using lactation and the mammary gland as a
      model system, we explore the hypothesis that chromatin state contributes to the
      co-regulation of gene neighborhoods. The mammary gland represents a unique
      evolutionary model, due to its recent appearance, in the context of vertebrate
      genomes. An understanding of how the mammary gland is regulated to produce milk
      is also of biomedical and agricultural importance for human lactation and
      dairying. Here, we integrate epigenomic and transcriptomic data to develop a
      comprehensive regulatory model. Neighborhoods of mammary-expressed genes were
      determined using expression data derived from pregnant and lactating mice and a
      neighborhood scoring tool, G-NEST. Regions of open and closed chromatin were
      identified by ChIP-Seq of histone modifications H3K36me3, H3K4me2, and H3K27me3
      in the mouse mammary gland and liver tissue during lactation. We found that
      neighborhoods of genes in regions of uniquely active chromatin in the lactating
      mammary gland, compared with liver tissue, were extremely rare. Rather, genes in
      most neighborhoods were suppressed during lactation as reflected in their
      expression levels and their location in regions of silenced chromatin. Chromatin
      silencing was largely shared between the liver and mammary gland during
      lactation, and what distinguished the mammary gland was mainly a small tissue
      specific repertoire of isolated, expressed genes. These findings suggest that an
      advantage of the neighborhood organization is in the collective repression of
      groups of genes via a shared mechanism of chromatin repression. Genes essential
      to the mammary gland's uniqueness are isolated from neighbors, and likely have
      less tolerance for variation in expression, properties they share with genes
      responsible for an organism's survival. 

PMID- 24086429
TI  - The small GTPase RhoB regulates TNFalpha signaling in endothelial cells.
AB  - The inflammatory response of endothelial cells triggered by cytokines such as
      TNFalpha and IL1beta plays a pivotal role in innate immunity. Upon pro
      inflammatory cytokine stimulation, endothelial cells produce chemokines and
      cytokines that attract and activate leukocytes, and express high levels of
      leukocyte adhesion molecules. This process is mediated by intracellular signaling
      cascades triggered by activation of e.g. the TNFalpha receptor (TNFR) that lead
      to the activation of the NFkappaB transcription factor and of MAP kinases, which
      in turn activate inflammatory gene transcription. We found that the small GTPase
      RhoB was strongly and rapidly upregulated in primary human endothelial cells by
      TNFalpha, IL1beta and LPS. We subsequently investigated the role of RhoB in the
      regulation of TNFR signaling in endothelial cells by silencing RhoB expression
      with siRNA. We provide evidence that the TNFalpha-induced activation of p38 MAP
      kinase is strongly dependent on RhoB, but not on RhoA, while JNK activation is
      regulated by both RhoB and RhoA. Consistent with the important role of p38 MAP
      kinase in inflammation, we demonstrate that loss of RhoB impairs TNFalpha-induced
      ICAM-1 expression and reduces cell production of IL6 and IL8. In addition, we
      show that RhoB silencing alters the intracellular traffic of TNFalpha after
      endocytosis. Since RhoB is a known regulator of the intracellular traffic of
      membrane receptors, our data suggest that RhoB controls TNFalpha signaling
      through the regulation of the TNFR traffic. 

PMID- 24086430
TI  - Increase in net activity of serine proteinases but not gelatinases after local
      endotoxin exposure in the peripheral airways of healthy subjects.
AB  - We tested the hypothesis that activation of the innate immune response induces an
      imbalance in the proteolytic homeostasis in the peripheral airways of healthy
      subjects, towards excess serine or gelatinase proteinase activity. During
      bronchoscopy, 18 healthy human subjects underwent intra-bronchial exposure to
      endotoxin and contra-lateral exposure to vehicle. Bronchoalveolar lavage (BAL)
      samples were harvested 24 or 48 hours (h) later. We quantified archetype
      proteinases, anti-proteinases, inflammatory BAL cells, and, importantly, total
      plus net proteinase activities using functional substrate assays. As expected,
      endotoxin exposure increased the concentrations of polymorphonuclear leukocytes
      (PMN's) and macrophages, of proteinases and the anti-proteinases tissue inhibitor
      of metalloproteinase-1, alpha-1-antitrypsin and, to a lesser extent, secretory
      leukoproteinase inhibitor, at both time points. Notably, at these time points,
      endotoxin exposure substantially increased the quantitative NE/SLPI ratio and the
      net serine proteinase activity corresponding to neutrophil elastase (NE).
      Endotoxin exposure also increased the total gelatinase activity corresponding to
      matrix metalloproteinase (MMP)-9; an activity dominating over that of MMP-2.
      However, endotoxin exposure had no impact on net gelatinolytic activity at 24 or
      48 h after exposure. Thus, local activation of the innate immune response induces
      an imbalance towards increased net serine proteinase activity in the proteolytic
      homeostasis of the peripheral airways in healthy subjects. Hypothetically, this
      serine proteinase activity can contribute to tissue remodelling and
      hypersecretion via NE from PMN's, if it is triggered repeatedly, as might be the
      case in chronic inflammatory airway disorders. 

PMID- 24086431
TI  - NOTCH3 variants and risk of ischemic stroke.
AB  - BACKGROUND: Mutations within the NOTCH3 gene cause cerebral autosomal dominant
      arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL). CADASIL
      mutations appear to be restricted to the first twenty-four exons, resulting in
      the gain or loss of a cysteine amino acid. The role of other exonic NOTCH3
      variation not involving cysteine residues and mutations in exons 25-33 in
      ischemic stroke remains unresolved. METHODS: All 33 exons of NOTCH3 were
      sequenced in 269 Caucasian probands from the Siblings With Ischemic Stroke Study
      (SWISS), a 70-center North American affected sibling pair study and 95 healthy
      Caucasian control subjects. Variants identified by sequencing in the SWISS
      probands were then tested for association with ischemic stroke using US Caucasian
      controls collected at the Mayo Clinic (n=654), and further assessed in a
      Caucasian (n=802) and African American (n=298) patient-control series collected
      through the Ischemic Stroke Genetics Study (ISGS). RESULTS: Sequencing of the 269
      SWISS probands identified one (0.4%) with small vessel type stroke carrying a
      known CADASIL mutation (p.R558C; Exon 11). Of the 19 common NOTCH3 variants
      identified, the only variant significantly associated with ischemic stroke after
      multiple testing adjustment was p.R1560P (rs78501403; Exon 25) in the combined
      SWISS and ISGS Caucasian series (Odds Ratio [OR] 0.50, P=0.0022) where presence
      of the minor allele was protective against ischemic stroke. Although only
      significant prior to adjustment for multiple testing, p.T101T (rs3815188; Exon 3)
      was associated with an increased risk of small-vessel stroke (OR: 1.56, P=0.008)
      and p.P380P (rs61749020; Exon 7) was associated with decreased risk of large
      vessel stroke (OR: 0.35, P=0.047) in Caucasians. No significant associations were
      observed in the small African American series. CONCLUSION: Cysteine-affecting
      NOTCH3 mutations are rare in patients with typical ischemic stroke, however our
      observation that common NOTCH3 variants may be associated with risk of ischemic
      stroke warrants further study.

PMID- 24086432
TI  - Aphanomyces euteiches cell wall fractions containing novel glucan
      chitosaccharides induce defense genes and nuclear calcium oscillations in the
      plant host Medicago truncatula.
AB  - N-acetylglucosamine-based saccharides (chitosaccharides) are components of
      microbial cell walls and act as molecular signals during host-microbe
      interactions. In the legume plant Medicago truncatula, the perception of
      lipochitooligosaccharide signals produced by symbiotic rhizobia and arbuscular
      mycorrhizal fungi involves the Nod Factor Perception (NFP) lysin motif receptor
      like protein and leads to the activation of the so-called common symbiotic
      pathway. In rice and Arabidopsis, lysin motif receptors are involved in the
      perception of chitooligosaccharides released by pathogenic fungi, resulting in
      the activation of plant immunity. Here we report the structural characterization
      of atypical chitosaccharides from the oomycete pathogen Aphanomyces euteiches,
      and their biological activity on the host Medicago truncatula. Using a
      combination of biochemical and biophysical approaches, we show that these
      chitosaccharides are linked to beta-1,6-glucans, and contain a beta-(1,3;1,4)
      glucan backbone whose beta-1,3-linked glucose units are substituted on their C-6
      carbon by either glucose or N-acetylglucosamine residues. This is the first
      description of this type of structural motif in eukaryotic cell walls. Glucan
      chitosaccharide fractions of A. euteiches induced the expression of defense
      marker genes in Medicago truncatula seedlings independently from the presence of
      a functional Nod Factor Perception protein. Furthermore, one of the glucan
      chitosaccharide fractions elicited calcium oscillations in the nucleus of root
      cells. In contrast to the asymmetric oscillatory calcium spiking induced by
      symbiotic lipochitooligosaccharides, this response depends neither on the Nod
      Factor Perception protein nor on the common symbiotic pathway. These findings
      open new perspectives in oomycete cell wall biology and elicitor recognition and
      signaling in legumes. 

PMID- 24086433
TI  - A small-animal pharmacokinetic/pharmacodynamic PET study of central serotonin 1A
      receptor occupancy by a potential therapeutic agent for overactive bladder.
AB  - Serotonin 1A (5-HT1A) receptors have been mechanistically implicated in
      micturition control, and there has been a need for an appropriate biomarker
      surrogating the potency of a provisional drug acting on this receptor system for
      developing a new therapeutic approach to overactive bladder (OAB). Here, we
      analyzed the occupancy of 5-HT1A receptors in living Sprague-Dawley rat brains by
      a novel candidate drug for OAB, E2110, using positron emission tomography (PET)
      imaging, and assessed the utility of a receptor occupancy (RO) assay to establish
      a pharmacodynamic index translatable between animals and humans. The plasma
      concentrations inducing 50% RO (EC50) estimated by both direct and effect
      compartment models were in good agreement. Dose-dependent therapeutic effects of
      E2110 on dysregulated micturition in different rat models of pollakiuria were
      also consistently explained by achievement of 5-HT1A RO by E2110 in a certain
      range (>= 60%). Plasma drug concentrations inducing this RO range and EC50 would
      accordingly be objective indices in comparing pharmacokinetics-RO relationships
      between rats and humans. These findings support the utility of PET RO and plasma
      pharmacokinetic assays with the aid of adequate mathematical models in
      determining the in vivo characteristics of a drug acting on 5-HT1A receptors and
      thereby counteracting OAB. 

PMID- 24086434
TI  - Extraocular muscle atrophy and central nervous system involvement in chronic
      progressive external ophthalmoplegia.
AB  - BACKGROUND: Chronic progressive external ophthalmoplegia (CPEO) is a classical
      mitochondrial ocular disorder characterised by bilateral progressive ptosis and
      ophthalmoplegia. These ocular features can develop either in isolation or in
      association with other prominent neurological deficits (CPEO+). Molecularly, CPEO
      can be classified into two distinct genetic subgroups depending on whether
      patients harbour single, large-scale mitochondrial DNA (mtDNA) deletions or
      multiple mtDNA deletions secondary to a nuclear mutation disrupting mtDNA
      replication or repair. The aim of this magnetic resonance imaging (MRI) study was
      to investigate whether the ophthalmoplegia in CPEO is primarily myopathic in
      origin or whether there is evidence of contributory supranuclear pathway
      dysfunction. METHODS: Ten age-matched normal controls and twenty patients with
      CPEO were recruited nine patients with single, large-scale mtDNA deletions and
      eleven patients with multiple mtDNA deletions secondary to mutations in POLG,
      PEO1, OPA1, and RRM2B. All subjects underwent a standardised brain and orbital
      MRI protocol, together with proton magnetic resonance spectroscopy in two voxels
      located within the parietal white matter and the brainstem. RESULTS: There was
      evidence of significant extraocular muscle atrophy in patients with single or
      multiple mtDNA deletions compared with controls. There was no significant
      difference in metabolite concentrations between the patient and control groups in
      both the parietal white matter and brainstem voxels. Volumetric brain
      measurements revealed marked cortical and cerebellar atrophy among patients with
      CPEO+ phenotypes. CONCLUSION: The results of this study support a primary
      myopathic aetiology for the progressive limitation of eye movements that develops
      in CPEO.

PMID- 24086435
TI  - High incidence of HPV-associated head and neck cancers in FA deficient mice is
      associated with E7's induction of DNA damage through its inactivation of pocket
      proteins.
AB  - Fanconi anemia (FA) patients are highly susceptible to solid tumors at multiple
      anatomical sites including head and neck region. A subset of head and neck
      cancers (HNCs) is associated with 'high-risk' HPVs, particularly HPV16. However,
      the correlation between HPV oncogenes and cancers in FA patients is still
      unclear. We previously learned that FA deficiency in mice predisposes HPV16 E7
      transgenic mice to HNCs. To address HPV16 E6's oncogenic potential under FA
      deficiency in HNCs, we utilized HPV16 E6-transgenic mice (K14E6) and HPV16 E6/E7
      bi-transgenic mice (K14E6E7) on genetic backgrounds sufficient or deficient for
      one of the fanc genes, fancD2 and monitored their susceptibility to HNCs. K14E6
      mice failed to develop tumor. However, E6 and fancD2-deficiency accelerated E7
      driven tumor development in K14E6E7 mice. The increased tumor incidence was more
      correlated with E7-driven DNA damage than proliferation. We also found that
      deficiency of pocket proteins, pRb, p107, and p130 that are well-established
      targets of E7, could recapitulate E7's induction of DNA damage. Our findings
      support the hypothesis that E7 induces HPV-associated HNCs by promoting DNA
      damage through the inactivation of pocket proteins, which explains why a
      deficiency in DNA damage repair would increase susceptibility to E7-driven
      cancer. Our results further demonstrate the unexpected finding that FA deficiency
      does not predispose E6 transgenic mice to HNCs, indicating a specificity in the
      synergy between FA deficiency and HPV oncogenes in causing HNCs. 

PMID- 24086436
TI  - Origins of Myc proteins--using intrinsic protein disorder to trace distant
      relatives.
AB  - Mammalian Myc proteins are important determinants of cell proliferation as well
      as the undifferentiated state of stem cells and their activity is frequently
      deregulated in cancer. Based mainly on conservation in the C-terminal DNA-binding
      and dimerization domain, Myc-like proteins have been reported in many simpler
      organisms within and outside the Metazoa but they have not been found in fungi or
      plants. Several important signature motifs defining mammalian Myc proteins are
      found in the N-terminal domain but the extent to which these are found in the Myc
      like proteins from simpler organisms is not well established. The extent of N
      terminal signature sequence conservation would give important insights about the
      evolution of Myc proteins and their current function in mammalian physiology and
      disease. In a systematic study of Myc-like proteins we show that N-terminal
      signature motifs are not readily detectable in individual Myc-like proteins from
      invertebrates but that weak similarities to Myc boxes 1 and 2 can be found in the
      N-termini of the simplest Metazoa as well as the unicellular choanoflagellate,
      Monosiga brevicollis, using multiple protein alignments. Phylogenetic support for
      the connections of these proteins to established Myc proteins is however poor. We
      show that the pattern of predicted protein disorder along the length of Myc
      proteins can be used as a complementary approach to making dendrograms of Myc
      proteins that aids the classification of Myc proteins. This suggests that the
      pattern of disorder within Myc proteins is more conserved through evolution than
      their amino acid sequence. In the disorder-based dendrograms the Myc-like
      proteins from simpler organisms, including M. brevicollis, are connected to
      established Myc proteins with a higher degree of certainty. Our results suggest
      that protein disorder based dendrograms may be of general significance for
      studying distant relationships between proteins, such as transcription factors,
      that have high levels of intrinsic disorder. 

PMID- 24086437
TI  - Differential expression of serotonin, tryptophan hydroxylase and monoamine
      oxidase A in the mammary gland of the Myotis velifer bat.
AB  - The mammary gland has long drawn the attention of the scientific community due to
      the limited knowledge of some fundamental aspects involved in the control of its
      function. Myotis velifer, a microchiropteran species, provides an interesting
      model to study some of the regulatory factors involved in the control of the
      mammary gland cycle. Having an asynchronous, monoestrous reproductive pattern,
      female M. velifer bats undergo drastic morphological changes of the breast during
      the reproductive cycle. Current research on non-chiropteran mammals indicates
      that serotonin (5-HT) plays a major role in the intraluminal volume homeostasis
      of the mammary gland during lactation; however, an analysis of both the
      expression and localization of the main components of the serotonergic system in
      the bat mammary gland is lacking. Thus, the objectives of the present study were:
      to describe the gross and histological anatomy of the mammary gland of M. velifer
      to establish the lactation period for this species; to analyze the distribution
      and expression of the main serotonergic components in the mammary tissues of
      these bats under the physiological conditions of lactation, involution and the
      resting phase; and to provide information on the involvement of 5-HT in the
      regulation of the physiological function of this organ. To assess the expression
      and localization of serotonergic components, multiple immunofluorescence, Western
      blot and HPLC methods were used. 5-HT and the enzyme that catalyzes its synthesis
      (TPH) were located in both myoepithelial and luminal epithelial cells, while the
      enzyme responsible for the catabolism of this neurohormone (MAO A) was found in
      luminal epithelial cells as well as in secreted products. We also found an
      increased expression of serotonergic components during lactation, indicating that
      elements of the serotonergic system may play an important role in lactation in
      this species of bat in a way similar to that of other mammal species. 

PMID- 24086438
TI  - Mapping the small RNA content of simian immunodeficiency virions (SIV).
AB  - Recent evidence indicates that regulatory small non-coding RNAs are not only
      components of eukaryotic cells and vesicles, but also reside within a number of
      different viruses including retroviral particles. Using ultra-deep sequencing we
      have comprehensively analyzed the content of simian immunodeficiency virions
      (SIV), which were compared to mock-control preparations. Our analysis revealed
      that more than 428,000 sequence reads matched the SIV mac239 genome sequence.
      Among these we could identify 12 virus-derived small RNAs (vsRNAs) that were
      highly abundant. Beside known retrovirus-enriched small RNAs, like 7SL-RNA,
      tRNA(Lys3) and tRNA(Lys) isoacceptors, we also identified defined fragments
      derived from small ILF3/NF90-associated RNA snaR-A14, that were enriched more
      than 50 fold in SIV. We also found evidence that small nucleolar RNAs U2 and U12
      were underrepresented in the SIV preparation, indicating that the relative number
      or the content of co-isolated exosomes was changed upon infection. Our
      comprehensive atlas of SIV-incorporated small RNAs provides a refined picture of
      the composition of retrovirions, which gives novel insights into viral packaging.

PMID- 24086439
TI  - Identification of proteins associated with polyhydroxybutyrate granules from
      Herbaspirillum seropedicae SmR1--old partners, new players.
AB  - Herbaspirillum seropedicae is a diazotrophic beta-Proteobacterium found
      associated with important agricultural crops. This bacterium produces
      polyhydroxybutyrate (PHB), an aliphatic polyester, as a carbon storage and/or
      source of reducing equivalents. The PHB polymer is stored as intracellular
      insoluble granules coated mainly with proteins, some of which are directly
      involved in PHB synthesis, degradation and granule biogenesis. In this work, we
      have extracted the PHB granules from H. seropedicae and identified their
      associated-proteins by mass spectrometry. This analysis allowed us to identify
      the main phasin (PhaP1) coating the PHB granule as well as the PHB synthase
      (PhbC1) responsible for its synthesis. A phbC1 mutant is impaired in PHB
      synthesis, confirming its role in H. seropedicae. On the other hand, a phaP1
      mutant produces PHB granules but coated mainly with the secondary phasin (PhaP2).
      Furthermore, some novel proteins not previously described to be involved with PHB
      metabolism were also identified, bringing new possibilities to PHB function in H.
      seropedicae. 

PMID- 24086440
TI  - Economic instruments for population diet and physical activity behaviour change:
      a systematic scoping review.
AB  - BACKGROUND: Unhealthy diet and low levels of physical activity are common
      behavioural factors in the aetiology of many non-communicable diseases. Recent
      years have witnessed an upsurge of policy and research interest in the use of
      taxes and other economic instruments to improve population health. OBJECTIVE: To
      assemble, configure and analyse empirical research studies available to inform
      the public health case for using economic instruments to promote dietary and
      physical activity behaviour change. METHODS: We conducted a systematic scoping
      review of evidence for the effects of specific interventions to change, or
      general exposure to variations in, prices or income on dietary and physical
      activity behaviours and corollary outcomes. Systematic electronic searches and
      parallel snowball searches retrieved >1 million study records. Text mining
      technologies were used to prioritise title-abstract records for screening.
      Eligible studies were selected, classified and analysed in terms of key
      characteristics and principal findings, using a narrative, configuring synthesis
      focused on implications for policy and further research. RESULTS: We identified
      880 eligible studies, including 192 intervention studies and 768 studies that
      incorporated evidence for prices or income as correlates or determinants of
      target outcomes. Current evidence for the effects of economic instruments and
      exposures on diet and physical activity is limited in quality and equivocal in
      terms of its policy implications. Direct evidence for the effects of economic
      instruments is heavily skewed towards impacts on diet, with a relative lack of
      evidence for impacts on physical activity. CONCLUSIONS: The evidence-based case
      for using economic instruments to promote dietary and physical activity behaviour
      change may be less compelling than some proponents have claimed. Future research
      should include measurement of people's actual behavioural responses using study
      designs capable of generating reliable causal inferences regarding intervention
      effects. Policy implementation needs to be carefully aligned with evaluation
      planning and design.

PMID- 24086442
TI  - Different traits determine introduction, naturalization and invasion success in
      woody plants: Proteaceae as a test case.
AB  - A major aim of invasion ecology is to identify characteristics of successful
      invaders. However, most plant groups studied in detail (e.g. pines and acacias)
      have a high percentage of invasive taxa. Here we examine the global introduction
      history and invasion ecology of Proteaceae--a large plant family with many taxa
      that have been widely disseminated by humans, but with few known invaders. To do
      this we compiled a global list of species and used boosted regression tree models
      to assess which factors are important in determining the status of a species (not
      introduced, introduced, naturalized or invasive). At least 402 of 1674 known
      species (24%) have been moved by humans out of their native ranges, 58 species
      (14%) have become naturalized but not invasive, and 8 species (2%) are invasive.
      The probability of naturalization was greatest for species with large native
      ranges, low susceptibility to Phytophthora root-rot fungus, large mammal
      dispersed seeds, and with the capacity to resprout. The probability of
      naturalized species becoming invasive was greatest for species with large native
      ranges, those used as barrier plants, tall species, species with small seeds, and
      serotinous species. The traits driving invasiveness of Proteaceae were similar to
      those for acacias and pines. However, while some traits showed a consistent
      influence at introduction, naturalization and invasion, others appear to be
      influential at one stage only, and some have contrasting effects at different
      stages. Trait-based analyses therefore need to consider different invasion stages
      separately. On their own, these observations provide little predictive power for
      risk assessment, but when the causative mechanisms are understood (e.g.
      Phytophthora susceptibility) they provide valuable insights. As such there is
      considerable value in seeking the correlates and mechanisms underlying invasions
      for particular taxonomic or functional groups.

PMID- 24086441
TI  - Protein kinase A and C regulate leak potassium currents in freshly isolated
      vascular myocytes from the aorta.
AB  - We tested the hypothesis that protein kinase A (PKA) inhibits K2P currents
      activated by protein kinase C (PKC) in freshly isolated aortic myocytes. PDBu,
      the PKC agonist, applied extracellularly, increased the amplitude of the K2P
      currents in the presence of the "cocktail" of K(+) channel blockers. Go 6976
      significantly reduced the increase of the K2P currents by PDBu suggesting the
      involvement of either alpha or beta isoenzymes of PKC. We found that forskolin,
      or membrane permeable cAMP, did not inhibit K2P currents activated by the PKC.
      However, when PKA agonists were added prior to PDBu, they produced a strong
      decrease in the K2P current amplitudes activated by PKC. Inhibition of PDBu
      elicited K2P currents by cAMP agonists was not prevented by the treatment of
      vascular smooth muscle cells with PKA antagonists (H-89 and Rp-cAMPs). Zn(2+) and
      Hg(2+) inhibited K2P currents in one population of cells, produced biphasic
      responses in another population, and increased the amplitude of the PDBu-elicited
      K(+) currents in a third population of myocytes, suggesting expression of several
      K2P channel types. We found that cAMP agonists inhibited biphasic responses and
      increase of amplitude of the PDBu-elicited K2P currents produced by Zn(2+) and
      Hg(2). 6-Bnz-cAMp produced a significantly altered pH sensitivity of PDBu
      elicited K2P-currents, suggesting the inhibition of alkaline-activated K2P
      currents. These results indicate that 6-Bnz-cAMP and other cAMP analogs may
      inhibit K2P currents through a PKA-independent mechanism. cAMP analogs may
      interact with unidentified proteins involved in K2P channel regulation. This
      novel cellular mechanism could provide insights into the interplay between PKC
      and PKA pathways that regulate vascular tone. 

PMID- 24086443
TI  - How to decrease suicide rates in both genders? An effectiveness study of a
      community-based intervention (EAAD).
AB  - BACKGROUND: The suicide rate in Hungary is high in international comparison. The
      two-year community-based four-level intervention programme of the European
      Alliance Against Depression (EAAD) is designed to improve the care of depression
      and to prevent suicidal behaviour. Our aim was to evaluate the effectiveness of a
      regional community-based four-level suicide prevention programme on suicide
      rates. METHOD: The EAAD programme was implemented in Szolnok (population 76,311),
      a town in a region of Hungary with an exceptionally high suicide rate.
      Effectiveness was assessed by comparing changes in suicide rates in the
      intervention region after the intervention started with changes in national
      suicide rates and those in a control region (Szeged) in the corresponding period.
      RESULTS: For the duration of the programme and the follow-up year, suicide rates
      in Szolnok were significantly lower than the average of the previous three years
      (p = .0076). The suicide rate thus went down from 30.1 per 100,000 in 2004 to
      13.2 in 2005 (-56.1 %), 14.6 in 2006 (-51.4 %) and 12.0 in 2007 (-60.1 %). This
      decrease of annual suicide rates in Szolnok after the onset of the intervention
      was significantly stronger than that observed in the whole country (p = .017) and
      in the control region (p = .0015). Men had the same decrease in suicide rates as
      women. As secondary outcome, an increase of emergency calls to the hotline
      service (200%) and outpatient visits at the local psychiatry clinic (76%) was
      found. CONCLUSIONS: These results seem to provide further support for the
      effectiveness of the EAAD concept. Whilst the majority of suicide prevention
      programs mainly affect female suicidal behaviour, this programme seems to be
      beneficial for both sexes. The sustainability and the role of the mediating
      factors (social service and health care utilization, community attitudes about
      suicide) should be key points in future research.

PMID- 24086444
TI  - Desmosomal cadherins are decreased in explanted arrhythmogenic right ventricular
      dysplasia/cardiomyopathy patient hearts.
AB  - AIMS: Arrhythmogenic right ventricular Dysplasia/cardiomyopathy (ARVD/C) is an
      autosomal dominant inherited cardiomyopathy associated with ventricular
      arrhythmia, heart failure and sudden death. Genetic studies have demonstrated the
      central role of desmosomal proteins in this disease, where 50% of patients harbor
      a mutation in a desmosmal gene. However, clinical diagnosis of the disease
      remains difficult and molecular mechanisms appears heterogeneous and poorly
      understood. The aim of this study was to characterize the expression profile of
      desmosomal proteins in explanted ARVD/C heart samples, in order to identify
      common features of the disease. METHODS AND RESULTS: We examined plakophilin-2,
      desmoglein-2, desmocollin-2, plakoglobin and beta-catenin protein expression
      levels from seven independent ARVD/C heart samples compared to two ischemic, five
      dilated cardiomyopathy and one healthy heart sample as controls. Ventricular and
      septum sections were examined by immunoblot analysis of total heart protein
      extracts and by immunostaining. Immunoblots indicated significant decreases in
      desmoglein-2 and desmocollin-2, independent of any known underlying mutations,
      whereas immune-histochemical analysis showed normal localization of all
      desmosomal proteins. Quantitative RT-PCR revealed normal DSG2 and DSC2 mRNA
      transcript levels, suggesting increased protein turn-over rather than
      transcriptional down regulation. CONCLUSION: Reduced cardiac desmoglein-2 and
      desmocollin-2 levels appear to be specifically associated with ARVD/C,
      independent of underlying mutations. These findings highlight a key role of
      desmosomal cadherins in the pathophysiology of ARVD/C. Whether these reductions
      could be considered as specific markers for ARVD/C requires replication analysis.

PMID- 24086445
TI  - Genome-wide association analysis with gray matter volume as a quantitative
      phenotype in first-episode treatment-naive patients with schizophrenia.
AB  - Reduced Gray matter (GM) volume is a core feature of schizophrenia. Mapping genes
      that is associated with the heritable disease-related phenotypes may be conducive
      to elucidate the pathogenesis of schizophrenia. This study aims to identify the
      common genetic variants that underlie the deficits of GM volume in schizophrenia.
      High-resolution T1 images and whole genome genotyping data were obtained from 74
      first-episode treatment-naive patients with schizophrenia and 51 healthy controls
      in the Mental Health Centre of the West China Hospital, Sichuan University. All
      participants were scanned using a 3T MR imaging system and were genotyped using
      the HumanHap660 Bead Array. Reduced GM volumes in three brain areas including
      right hOC3v in the collateral sulcus of visual cortex (hOC3vR), left cerebellar
      vermis lobule 10 (vermisL10) and right cerebellar vermis lobule 10 (vermisR10)
      were found in patients with schizophrenia [corrected].There was a group by
      genotype interaction when genotypes from genome-wide scan were subsequently
      considered in the case-control analyses. SNPs from three genes or chromosomal
      regions (TBXAS1, PIK3C2G and HS3ST5) were identified to predict the changes of GM
      volume in hOC3vL, vermisL10 and vermisR10. These results also highlighted the
      usefulness of endophenotype in exploring the pathogenesis of neuropsychiatric
      diseases such as schizophrenia although further independent replication studies
      are needed in the future.

PMID- 24086446
TI  - Mortality and recurrence risk in relation to the use of lipid-lowering drugs in a
      prospective breast cancer patient cohort.
AB  - Lipid-lowering drugs are used for the prevention of cardiovascular diseases.
      Statins are the most commonly used lipid-lowering drugs. Evidence from
      preclinical and observational studies suggests that statins might improve the
      prognosis of breast cancer patients. We analyzed data from the German MARIEplus
      study, a large prospective population-based cohort of patients aged 50 and older,
      who were diagnosed with breast cancer between 2001 and 2005. For overall
      mortality, breast-cancer specific mortality, and non-breast-cancer mortality, we
      included 3189 patients with invasive breast cancer stage I-IV, and for recurrence
      risk 3024 patients with breast cancer stage I-III. We used Cox proportional
      hazards models to assess the association with self-reported lipid-lowering drug
      use at recruitment. We stratified by study region, tumor grade, and
      estrogen/progesterone receptor status, and adjusted for age, tumor size, nodal
      status, metastases (stage I-IV only), menopausal hormone treatment, mode of
      detection, radiotherapy, and smoking. Mortality analyses were additionally
      adjusted for cardiovascular disease, diabetes mellitus and body-mass index.
      During a median follow-up of 5.3 years, 404 of 3189 stage I-IV patients died, and
      286 deaths were attributed to breast cancer. Self-reported use of lipid-lowering
      drugs was non-significantly associated with increased non-breast cancer mortality
      (Hazard ratio (HR) 1.49, 95% confidence interval (CI) 0.88-2.52) and increased
      overall mortality (HR 1.21, 95% CI 0.87-1.69) whereas no association with breast
      cancer-specific mortality was found (HR 1.04, 0.67-1.60). Restricted to stage I
      III breast cancer patients, 387 recurrences occurred during a median follow-up of
      5.4 years. We found lipid-lowering drug use to be non-significantly associated
      with a reduced risk of recurrence (HR 0.83, 95% CI 0.54-1.24) and of breast
      cancer-specific mortality (HR 0.89, 95% CI 0.52-1.49). Although compatible with
      previous findings of an improved prognosis associated with statin use, our
      results do not provide clear supportive evidence for an association with lipid
      lowering drug use due to imprecise estimates. 

PMID- 24086447
TI  - Effect of the Mahatma Gandhi National Rural Employment Guarantee Act (MGNREGA) on
      malnutrition of infants in Rajasthan, India: a mixed methods study.
AB  - OBJECTIVES: Analyse the effect of the Mahatma Gandhi National Rural Employment
      Guarantee Act (MGNREGA), a wage-for-employment policy of the Indian Government,
      on infant malnutrition and delineate the pathways through which MGNREGA affects
      infant malnutrition. HYPOTHESIS: MGNREGA could reduce infant malnutrition through
      positive effects on household food security and infant feeding. METHOD: Mixed
      methods using cross-sectional study and focus group discussions conducted in
      Dungarpur district, Rajasthan, India. PARTICIPANTS: Infants aged 1 to <12 months
      and their mothers/caregivers. Final sample 528 households with 1056 participants,
      response rate 89.6%. Selected households were divided into MGNREGA-households and
      non-MGNREGA-households based on participation in MGNREGA between August-2010 and
      September-2011. OUTCOMES: Infant malnutrition measured using anthropometric
      indicators - underweight, stunting, and wasting (WHO criteria). RESULTS: We
      included 528 households with 1,056 participants. Out of 528, 281 households took
      part in MGNREGA between August'10, and September'11. Prevalence of wasting was
      39%, stunting 24%, and underweight 50%. Households participating in MGNREGA were
      less likely to have wasted infants (OR 0.57, 95% CI 0.37-0.89, p = 0.014) and
      less likely to have underweight infants (OR 0.48, 95% CI 0.30-0.76, p = 0.002)
      than non-participating households. Stunting did not differ significantly between
      groups. We did 11 focus group discussions with 62 mothers. Although MGNREGA
      reduced starvation, it did not provide the desired benefits because of lower than
      standard wages and delayed payments. Results from path analysis did not support
      existence of an effect through household food security and infant feeding, but
      suggested a pathway of effect through low birth-weight. CONCLUSION: Participation
      in MGNREGA was associated with reduced infant malnutrition possibly mediated
      indirectly via improved birth-weight rather than by improved infant feeding.
      Addressing factors such as lack of mothers' knowledge and inappropriate feeding
      practices, over and above the social and economic policies, is key in efforts to
      reduce infant malnutrition.

PMID- 24086448
TI  - Thyrotropin regulates IL-6 expression in CD34+ fibrocytes: clear delineation of
      its cAMP-independent actions.
AB  - IL-6 plays diverse roles in normal and disease-associated immunity such as that
      associated with Graves' disease (GD). In that syndrome, the orbit undergoes
      remodeling during a process known as thyroid-associated ophthalmopathy (TAO).
      Recently, CD34(+) fibrocytes were found to infiltrate the orbit in TAO where they
      transition into CD34(+) orbital fibroblasts. Surprisingly, fibrocytes display
      high levels of functional thyrotropin receptor (TSHR), the central antigen in GD.
      We report here that TSH and the pathogenic anti-TSHR antibodies that drive
      hyperthyroidism in GD induce IL-6 expression in fibrocytes and orbital
      fibroblasts. Unlike TSHR signaling in thyroid epithelium, that occurring in
      fibrocytes is completely independent of adenylate cyclase activation and cAMP
      generation. Instead TSH activates PDK1 and both AKT/PKB and PKC pathways.
      Expression and use of PKCbetaII switches to that of PKCu as fibrocytes transition
      to TAO orbital fibroblasts. This shift is imposed by CD34(-) orbital fibroblasts
      but reverts when CD34(+) fibroblasts are isolated. The up-regulation of IL-6 by
      TSH results from coordinately enhanced IL-6 gene promoter activity and increased
      IL-6 mRNA stability. TSH-dependent IL-6 expression requires activity at both CREB
      (-213 to -208 nt) and NF-kappaB (-78 to -62 nt) binding sites. These results
      provide novel insights into the molecular action of TSH and signaling downstream
      for TSHR in non-thyroid cells. Fibrocytes neither express adenylate cyclase nor
      generate cAMP and thus these findings are free from any influence of cAMP-related
      signaling. They identify potential therapeutic targets for TAO. 

PMID- 24086449
TI  - Keratin 8 is required for the maintenance of architectural structure in thymus
      epithelium.
AB  - Keratins (Ks), the intermediate filament (IF) proteins of epithelia, are
      coordinately expressed as pairs in a cell-lineage and differentiation manner.
      Cortical thymic epithelial cells (cTECs) predominantly express the simple
      epithelium keratin 8/18 (K8/K18) pair, whereas medullary thymic epithelial cells
      (mTECs) express the stratified epithelium K5/K14 pair, with TECs exhibiting K5
      and K8 at the cortico-medullary junction in mature thymus. In the work reported
      here, we used wild-type (WT) and K8-knockout (K8-null) mice to address the
      contribution of K8/K18 IFs in the maintenance of the thymic epithelial structure.
      K8-null thymus maintained the differential cell segregation at the cortex versus
      the medulla observed in WT thymus, and the distribution of immature thymocytes at
      the cortex. The K8/K18 loss did not affect thymocyte development. However, it
      massively perturbed the TEC morphology both at the cortex and the medulla, along
      with a prominent depletion of cTECs. Such tissue alterations coincided with an
      increase in apoptosis and a reduced expression of Albatross (Fas-binding factor
      1), also known for its capacity to bind K8/18 IFs. In addition, the K8/K18 loss
      affected the distribution of K5/K14-positive mTECs, but not their differentiation
      status. Together, the results indicate that K8/K18 IFs constitute key promoters
      of the thymic epithelium integrity. 

PMID- 24086450
TI  - Mutant huntingtin gene-dose impacts on aggregate deposition, DARPP32 expression
      and neuroinflammation in HdhQ150 mice.
AB  - Huntington's disease (HD) is an autosomal dominant, progressive and fatal
      neurological disorder caused by an expansion of CAG repeats in exon-1 of the
      huntingtin gene. The encoded poly-glutamine stretch renders mutant huntingtin
      prone to aggregation. HdhQ150 mice genocopy a pathogenic repeat (~150 CAGs) in
      the endogenous mouse huntingtin gene and model predominantly pre-manifest HD.
      Treating early is likely important to prevent or delay HD, and HdhQ150 mice may
      be useful to assess therapeutic strategies targeting pre-manifest HD. This
      requires appropriate markers and here we demonstrate, that pre-symptomatic
      HdhQ150 mice show several dramatic mutant huntingtin gene-dose dependent
      pathological changes including: (i) an increase of neuronal intra-nuclear
      inclusions (NIIs) in brain, (ii) an increase of extra-nuclear aggregates in
      dentate gyrus, (iii) a decrease of DARPP32 protein and (iv) an increase in glial
      markers of neuroinflammation, which curiously did not correlate with local
      neuronal mutant huntingtin inclusion-burden. HdhQ150 mice developed NIIs also in
      all retinal neuron cell-types, demonstrating that retinal NIIs are not specific
      to human exon-1 R6 HD mouse models. Taken together, the striking and robust
      mutant huntingtin gene-dose related changes in aggregate-load, DARPP32 levels and
      glial activation markers should greatly facilitate future testing of therapeutic
      strategies in the HdhQ150 HD mouse model. 

PMID- 24086451
TI  - beta1 integrin binding phosphorylates ezrin at T567 to activate a lipid raft
      signalsome driving invadopodia activity and invasion.
AB  - Extracellular matrix (ECM) degradation is a critical process in tumor cell
      invasion and requires matrix degrading protrusions called invadopodia. The
      Na(+)/H(+) exchanger (NHE1) has recently been shown to be fundamental in the
      regulation of invadopodia actin cytoskeleton dynamics and activity. However, the
      structural link between the invadopodia cytoskeleton and NHE1 is still unknown. A
      candidate could be ezrin, a linker between the NHE1 and the actin cytoskeleton
      known to play a pivotal role in invasion and metastasis. However, the mechanistic
      basis for its role remains unknown. Here, we demonstrate that ezrin
      phosphorylated at T567 is highly overexpressed in the membrane of human breast
      tumors and positively associated with invasive growth and HER2 overexpression.
      Further, in the metastatic cell line, MDA-MB-231, p-ezrin was almost exclusively
      expressed in invadopodia lipid rafts where it co-localized in a functional
      complex with NHE1, EGFR, beta1-integrin and phosphorylated-NHERF1. Manipulation
      by mutation of ezrins T567 phosphorylation state and/or PIP2 binding capacity or
      of NHE1s binding to ezrin or PIP2 demonstrated that p-ezrin expression and
      binding to PIP2 are required for invadopodia-mediated ECM degradation and
      invasion and identified NHE1 as the membrane protein that p-ezrin regulates to
      induce invadopodia formation and activity. 

PMID- 24086452
TI  - The mitochondrial genome impacts respiration but not fermentation in
      interspecific Saccharomyces hybrids.
AB  - In eukaryotes, mitochondrial DNA (mtDNA) has high rate of nucleotide substitution
      leading to different mitochondrial haplotypes called mitotypes. However, the
      impact of mitochondrial genetic variant on phenotypic variation has been poorly
      considered in microorganisms because mtDNA encodes very few genes compared to
      nuclear DNA, and also because mitochondrial inheritance is not uniparental. Here
      we propose original material to unravel mitotype impact on phenotype: we produced
      interspecific hybrids between S. cerevisiae and S. uvarum species, using fully
      homozygous diploid parental strains. For two different interspecific crosses
      involving different parental strains, we recovered 10 independent hybrids per
      cross, and allowed mtDNA fixation after around 80 generations. We developed PCR
      based markers for the rapid discrimination of S. cerevisiae and S. uvarum
      mitochondrial DNA. For both crosses, we were able to isolate fully isogenic
      hybrids at the nuclear level, yet possessing either S. cerevisiae mtDNA (Sc
      mtDNA) or S. uvarum mtDNA (Su-mtDNA). Under fermentative conditions, the mitotype
      has no phenotypic impact on fermentation kinetics and products, which was
      expected since mtDNA are not necessary for fermentative metabolism.
      Alternatively, under respiratory conditions, hybrids with Sc-mtDNA have higher
      population growth performance, associated with higher respiratory rate. Indeed,
      far from the hypothesis that mtDNA variation is neutral, our work shows that
      mitochondrial polymorphism can have a strong impact on fitness components and
      hence on the evolutionary fate of the yeast populations. We hypothesize that
      under fermentative conditions, hybrids may fix stochastically one or the other mt
      DNA, while respiratory environments may increase the probability to fix Sc-mtDNA.

PMID- 24086453
TI  - Hippocampal neurogenesis levels predict WATERMAZE search strategies in the aging
      brain.
AB  - The hippocampus plays a crucial role in the formation of spatial memories, and it
      is thought that adult hippocampal neurogenesis may participate in this form of
      learning. To better elucidate the relationship between neurogenesis and spatial
      learning, we examined both across the entire life span of mice. We found that
      cell proliferation, neuronal differentiation, and neurogenesis significantly
      decrease with age, and that there is an abrupt reduction in these processes early
      on, between 1.5-3 months of age. After this, the neurogenic capacity continues to
      decline steadily. The initial abrupt decline in adult neurogenesis was paralleled
      by a significant reduction in Morris Water Maze performance, however overall
      learning and memory remained constant thereafter. Further analysis of the search
      strategies employed revealed that reductions in neurogenesis in the aging brain
      were strongly correlated with the adoption of spatially imprecise search
      strategies. Overall, performance measures of learning and memory in the Morris
      Water Maze were maintained at relatively constant levels in aging animals due to
      an increase in the use of spatially imprecise search strategies. 

PMID- 24086454
TI  - Selection of single domain antibodies from immune libraries displayed on the
      surface of E. coli cells with two beta-domains of opposite topologies.
AB  - Screening of antibody (Ab) libraries by direct display on the surface of E. coli
      cells is hampered by the presence of the outer membrane (OM). In this work we
      demonstrate that the native beta-domains of EhaA autotransporter and intimin, two
      proteins from enterohemorrhagic E. coli O157:H7 (EHEC) with opposite topologies
      in the OM, are effective systems for the display of immune libraries of single
      domain Abs (sdAbs) from camelids (nanobodies or VHH) on the surface of E. coli K
      12 cells and for the selection of high affinity sdAbs using magnetic cell sorting
      (MACS). We analyzed the capacity of EhaA and intimin beta-domains to display
      individual sdAbs and sdAb libraries obtained after immunization with the
      extracellular domain of the translocated intimin receptor from EHEC (TirM(EHEC)).
      We demonstrated that both systems displayed functional sdAbs on the surface of E.
      coli cells with little proteolysis and cellular toxicity, although E. coli cells
      displaying sdAbs with the beta-domain of intimin showed higher antigen-binding
      capacity. Both E. coli display libraries were screened for TirM(EHEC) binding
      clones by MACS. High affinity binders were selected by both display systems,
      although more efficiently with the intimin beta-domain. The specificity of the
      selected clones against TirM(EHEC) was demonstrated by flow cytometry of E. coli
      cells, along with ELISA and surface plasmon resonance with purified sdAbs.
      Finally, we employed the E. coli cell display systems to provide an estimation of
      the affinity of the selected sdAb by flow cytometry analysis under equilibrium
      conditions.

PMID- 24086455
TI  - T-cell intracellular antigen (TIA)-proteins deficiency in murine embryonic
      fibroblasts alters cell cycle progression and induces autophagy.
AB  - Mice lacking either T-cell intracellular antigen 1 (TIA1) or TIA1 related/like
      protein (TIAR/TIAL1) show high rates of embryonic lethality, suggesting a
      relevant role for these proteins during embryonic development. However, intrinsic
      molecular and cellular consequences of either TIA1 or TIAR deficiency remain
      poorly defined. By using genome-wide expression profiling approach, we
      demonstrate that either TIA1 or TIAR inactivation broadly alter normal
      development-associated signalling pathways in murine embryonic fibroblasts (MEF).
      Indeed, these analyses highlighted alterations of cytokine-cytokine and ECM
      receptor interactions and Wnt, MAPK, TGF-beta dependent signalling pathways.
      Consistent with these results, TIA1 and TIAR knockout (KO) MEF show reduced rates
      of cell proliferation, cell cycle progression delay and increased cell size.
      Furthermore, TIA-proteins deficiency also caused metabolic deficiencies,
      increased ROS levels and DNA damage, promoting a gentle rise of cell death.
      Concomitantly, high rates of autophagy were detected in both TIA1 and TIAR KO MEF
      with induction of the formation of autophagosomes, as evidenced by the up
      regulation of the LC3B protein, and autolysosomes, measured by colocalization of
      LC3B and LAMP1, as a survival mechanism attempt. Taken together, these
      observations support that TIA proteins orchestrate a transcriptome programme to
      activate specific developmental decisions. This program is likely to contribute
      to mouse physiology starting at early stages of the embryonic development.
      TIA1/TIAR might function as cell sensors to maintain homeostasis and promote
      adaptation/survival responses to developmental stress. 

PMID- 24086456
TI  - Toxoplasma gondii soluble tachyzoite antigen triggers protective mechanisms
      against fatal intestinal pathology in oral infection of C57BL/6 mice.
AB  - Toxoplasma gondii induces a potent IL-12 response early in infection that results
      in IFN-gamma-dependent control of parasite growth. It was previously shown that
      T. gondii soluble tachyzoite antigen (STAg) injected 48 hr before intraperitoneal
      infection reduces lipoxin A4 and 5-lipoxygenase (5-LO)-dependent systemic IL-12
      and IFN-gamma production as well as hepatic immunopathology. This study
      investigated the ability of STAg-pretreatment to control the fatal intestinal
      pathology that develops in C57BL/6 mice orally infected with 100 T. gondii cysts.
      STAg-pretreatment prolonged the animals' survival by decreasing tissue parasitism
      and pathology, mainly in the ilea. Protection was associated with decreases in
      the systemic IFN-gamma levels and IFN-gamma and TNF message levels in the ilea
      and with increased TGF-beta production in this tissue, but protection was
      independent of 5-LO and IL-4. STAg-pretreatment decreased CD4(+) T cell, NK cell,
      CD11b(+) monocyte and CD11b(+)CD11c(+) dendritic cell numbers in the lamina
      propria and increased CD8(+) T cells in the intestinal epithelial compartment. In
      parallel, decreases were observed in iNOS and IL-17 expression in this organ.
      These results demonstrate that pretreatment with STAg can induce the recruitment
      of protective CD8(+) T cells to the intraepithelial compartment and decrease
      proinflammatory immune mechanisms that promote intestinal pathology in T. gondii
      infection. 

PMID- 24086457
TI  - Workaholism as a risk factor for depressive mood, disabling back pain, and
      sickness absence.
AB  - OBJECTIVES: Although it is understood that work-related factors, including job
      demands, job control, and workplace support, are associated with workers' health
      and well-being, the role played by personal characteristics, especially
      workaholism, has not been fully investigated. This study examined workaholism's
      associations with psychological ill health, low back pain with disability, and
      sickness absence among Japanese workers. METHODS: A cross-sectional Internet
      survey was conducted using self-administered questionnaires. Data from 3,899
      Japanese workers were analyzed. Workaholism was measured using the Dutch
      Workaholism Scale (DUWAS). Scores were divided into tertiles, where respondents
      were classified into three groups (high, middle, and low). Depressive mood as a
      measure of psychological ill health was assessed using the SF-36 mental health
      subscale, and low back pain using a standardized question. Sickness absence,
      except that due to physical injuries, was categorized either as absence due to
      mental health problems or to physical/somatic problems including the common cold.
      Multiple logistic regression analyses were conducted to examine the association
      between workaholism and depressive mood, low back pain with disability, and
      sickness absence, adjusting for demographic characteristics, job demand, job
      control, and workplace support. RESULTS: Compared to the low workaholism group,
      the middle and high workaholism groups had significantly higher odds for
      depressive mood (Odds ratio (OR) = 1.93 and 3.62 for the middle and high groups,
      respectively), disabling back pain (ORs = 1.36 and 1.77 for the middle and high
      groups, respectively). Workaholism was more strongly associated with sickness
      absence due to mental health problems than that for other reasons (ORs = 1.76 vs.
      1.21 for the middle group and 3.52 vs. 1.37 for the high groups). CONCLUSIONS:
      Workaholism is significantly associated with poor psychological health, disabling
      back pain, and sickness absence, particularly from mental health problems.
      Therefore, workaholism must be considered when addressing well-being of workers.

PMID- 24086458
TI  - Characterization of naturally-occurring humoral immunity to AAV in sheep.
AB  - AAV vectors have shown great promise for clinical gene therapy (GT), but pre
      existing human immunity against the AAV capsid often limits transduction. Thus,
      testing promising AAV-based GT approaches in an animal model with similar pre
      existing immunity could better predict clinical outcome. Sheep have long been
      used for basic biological and preclinical studies. Moreover, we have re
      established a line of sheep with severe hemophilia A (HA). Given the impetus to
      use AAV-based GT to treat hemophilia, we characterized the pre-existing ovine
      humoral immunity to AAV. ELISA revealed naturally-occurring antibodies to AAV1,
      AAV2, AAV5, AAV6, AAV8, and AAV9. For AAV2, AAV8, and AAV9 these inhibit
      transduction in a luciferase-based neutralization assay. Epitope mapping
      identified peptides that were common to the capsids of all AAV serotypes tested
      (AAV2, AAV5, AAV8 and AAV9), with each animal harboring antibodies to unique and
      common capsid epitopes. Mapping using X-ray crystallographic AAV capsid
      structures demonstrated that these antibodies recognized both surface epitopes
      and epitopes located within regions of the capsid that are internal or buried in
      the capsid structure. These results suggest that sheep harbor endogenous AAV,
      which induces immunity to both intact capsid and to capsid epitopes presented
      following proteolysis during the course of infection. In conclusion, their
      clinically relevant physiology and the presence of naturally-occurring antibodies
      to multiple AAV serotypes collectively make sheep a unique model in which to
      study GT for HA, and other diseases, and develop strategies to circumvent the
      clinically important barrier of pre-existing AAV immunity. 

PMID- 24086459
TI  - The IRAK homolog Pelle is the functional counterpart of IkappaB kinase in the
      Drosophila Toll pathway.
AB  - Toll receptors transduce signals that activate Rel-family transcription factors,
      such as NF-kappaB, by directing proteolytic degradation of inhibitor proteins. In
      mammals, the IkappaB Kinase (IKK) phosphorylates the inhibitor IkappaBalpha. A
      betaTrCP protein binds to phosphorylated IkappaBalpha, triggering ubiquitination
      and proteasome mediated degradation. In Drosophila, Toll signaling directs Cactus
      degradation via a sequence motif that is highly similar to that in IkappaBalpha,
      but without involvement of IKK. Here we show that Pelle, the homolog of a
      mammalian regulator of IKK, acts as a Cactus kinase. We further find that the fly
      betaTrCP protein Slimb is required in cultured cells to mediate Cactus
      degradation. These findings enable us for the first time to trace an
      uninterrupted pathway from the cell surface to the nucleus for Drosophila Toll
      signaling. 

PMID- 24086460
TI  - Habitat-forming bryozoans in New Zealand: their known and predicted distribution
      in relation to broad-scale environmental variables and fishing effort.
AB  - Frame-building bryozoans occasionally occur in sufficient densities in New
      Zealand waters to generate habitat for other macrofauna. The environmental
      conditions necessary for bryozoans to generate such habitat, and the
      distributions of these species, are poorly known. Bryozoan-generated habitats are
      vulnerable to bottom fishing, so knowledge of species' distributions is essential
      for management purposes. To better understand these distributions, presence
      records were collated and mapped, and habitat suitability models were generated
      (Maxent, 1 km(2) grid) for the 11 most common habitat-forming bryozoan species:
      Arachnopusia unicornis, Cellaria immersa, Cellaria tenuirostris, Celleporaria
      agglutinans, Celleporina grandis, Cinctipora elegans, Diaperoecia purpurascens,
      Galeopsis porcellanicus, Hippomenella vellicata, Hornera foliacea, and Smittoidea
      maunganuiensis. The models confirmed known areas of habitat, and indicated other
      areas as potentially suitable. Water depth, vertical water mixing, tidal
      currents, and water temperature were useful for describing the distribution of
      the bryozoan species at broad scales. Areas predicted as suitable for multiple
      species were identified, and these 'hotspots' were compared to fishing effort
      data. This showed a potential conflict between fishing and the conservation of
      bryozoan-generated habitat. Fishing impacts are known from some sites, but damage
      to large areas of habitat-forming bryozoans is likely to have occurred throughout
      the study area. In the present study, spatial error associated with the use of
      historic records and the coarse native resolution of the environmental variables
      limited both the resolution at which the models could be interpreted and our
      understanding of the ecological requirements of the study species. However, these
      models show species distribution modelling has potential to further our
      understanding of habitat-forming bryozoan ecology and distribution. Importantly,
      comparisons between hotspots of suitable habitat and the distribution of bottom
      fishing in the study area highlight the need for management measures designed to
      mitigate the impact of seafloor disturbance on bryozoan-generated habitat in New
      Zealand waters.

PMID- 24086461
TI  - A sequence identification measurement model to investigate the implicit learning
      of metrical temporal patterns.
AB  - Implicit learning (IL) occurs unconsciously and without intention. Perceptual
      fluency is the ease of processing elicited by previous exposure to a stimulus. It
      has been assumed that perceptual fluency is associated with IL. However, the role
      of perceptual fluency following IL has not been investigated in temporal pattern
      learning. Two experiments by Schultz, Stevens, Keller, and Tillmann demonstrated
      the IL of auditory temporal patterns using a serial reaction-time task and a
      generation task based on the process dissociation procedure. The generation task
      demonstrated that learning was implicit in both experiments via motor fluency,
      that is, the inability to suppress learned information. With the aim to
      disentangle conscious and unconscious processes, we analyze unreported
      recognition data associated with the Schultz et al. experiments using the
      sequence identification measurement model. The model assumes that perceptual
      fluency reflects unconscious processes and IL. For Experiment 1, the model
      indicated that conscious and unconscious processes contributed to recognition of
      temporal patterns, but that unconscious processes had a greater influence on
      recognition than conscious processes. In the model implementation of Experiment
      2, there was equal contribution of conscious and unconscious processes in the
      recognition of temporal patterns. As Schultz et al. demonstrated IL in both
      experiments using a generation task, and the conditions reported here in
      Experiments 1 and 2 were identical, two explanations are offered for the
      discrepancy in model and behavioral results based on the two tasks: 1) perceptual
      fluency may not be necessary to infer IL, or 2) conscious control over implicitly
      learned information may vary as a function of perceptual fluency and motor
      fluency. 

PMID- 24086462
TI  - Population expansion and genetic structure in Carcharhinus brevipinna in the
      southern Indo-Pacific.
AB  - BACKGROUND: Quantifying genetic diversity and metapopulation structure provides
      insights into the evolutionary history of a species and helps develop appropriate
      management strategies. We provide the first assessment of genetic structure in
      spinner sharks (Carcharhinus brevipinna), a large cosmopolitan carcharhinid,
      sampled from eastern and northern Australia and South Africa. METHODS AND
      FINDINGS: Sequencing of the mitochondrial DNA NADH dehydrogenase subunit 4 gene
      for 430 individuals revealed 37 haplotypes and moderately high haplotype
      diversity (h = 0.6770 +/-0.025). While two metrics of genetic divergence (PhiST
      and F ST) revealed somewhat different results, subdivision was detected between
      South Africa and all Australian locations (pairwise PhiST, range 0.02717-0.03508,
      p values <= 0.0013; pairwise F ST South Africa vs New South Wales = 0.04056, p =
      0.0008). Evidence for fine-scale genetic structuring was also detected along
      Australia's east coast (pairwise PhiST = 0.01328, p < 0.015), and between south
      eastern and northern locations (pairwise PhiST = 0.00669, p < 0.04). CONCLUSIONS:
      The Indian Ocean represents a robust barrier to contemporary gene flow in C.
      brevipinna between Australia and South Africa. Gene flow also appears restricted
      along a continuous continental margin in this species, with data tentatively
      suggesting the delineation of two management units within Australian waters.
      Further sampling, however, is required for a more robust evaluation of the latter
      finding. Evidence indicates that all sampled populations were shaped by a
      substantial demographic expansion event, with the resultant high genetic
      diversity being cause for optimism when considering conservation of this
      commercially-targeted species in the southern Indo-Pacific.

PMID- 24086463
TI  - The motor system contributes to comprehension of abstract language.
AB  - If language comprehension requires a sensorimotor simulation, how can abstract
      language be comprehended? We show that preparation to respond in an upward or
      downward direction affects comprehension of the abstract quantifiers "more and
      more" and "less and less" as indexed by an N400-like component. Conversely, the
      semantic content of the sentence affects the motor potential measured immediately
      before the upward or downward action is initiated. We propose that this
      bidirectional link between motor system and language arises because the motor
      system implements forward models that predict the sensory consequences of
      actions. Because the same movement (e.g., raising the arm) can have multiple
      forward models for different contexts, the models can make different predictions
      depending on whether the arm is raised, for example, to place an object or raised
      as a threat. Thus, different linguistic contexts invoke different forward models,
      and the predictions constitute different understandings of the language. 

PMID- 24086464
TI  - Heat shock protein 70 is associated with replicase complex of Japanese
      encephalitis virus and positively regulates viral genome replication.
AB  - Japanese encephalitis virus (JEV) is a mosquito-borne flavivirus that causes the
      most prevalent viral encephalitis in Asia. The NS5 protein of JEV is a key
      component of the viral replicase complex, which plays a crucial role in viral
      pathogenesis. In this study, tandem affinity purification (TAP) followed by mass
      spectrometry analysis was performed to identify novel host proteins that interact
      with NS5. Heat shock protein 70 (Hsp70), eukaryotic elongation factor 1-alpha
      (eEF-1alpha) and ras-related nuclear protein (Ran) were demonstrated to interact
      with NS5. In addition to NS5, Hsp70 was also found to interact with NS3 which is
      another important member of the replicase complex. It was observed that the
      cytoplasmic Hsp70 partially colocalizes with the components of viral replicase
      complex including NS3, NS5 and viral dsRNA during JEV infection. Knockdown of
      Hsp70 resulted in a significantly reduced JEV genome replication. Further
      analysis reveals that Hsp70 enhances the stability of viral proteins in JEV
      replicase complex. These results suggest an important role for Hsp70 in
      regulating JEV replication, which provides a potential target for the development
      of anti-JEV therapies. 

PMID- 24086465
TI  - Development of a new DNA vaccine for Alzheimer disease targeting a wide range of
      abeta species and amyloidogenic peptides.
AB  - It has recently been determined that not only Abeta oligomers, but also other
      Abeta species and amyloidogenic peptides are neurotoxic in Alzheimer disease (AD)
      and play a pivotal role in AD pathogenesis. In the present study, we attempted to
      develop new DNA vaccines targeting a wide range of Abeta species. For this
      purpose, we first performed in vitro assays with newly developed vaccines to
      evaluate Abeta production and Abeta secretion abilities and then chose an IgL
      Abetax4-Fc-IL-4 vaccine (designated YM3711) for further studies. YM3711 was
      vaccinated to mice, rabbits and monkeys to evaluate anti-Abeta species antibody
      producing ability and Abeta reduction effects. It was found that YM3711
      vaccination induced significantly higher levels of antibodies not only to Abeta1
      42 but also to AD-related molecules including AbetapE3-42, Abeta oligomers and
      Abeta fibrils. Importantly, YM3711 significantly reduced these Abeta species in
      the brain of model mice. Binding and competition assays using translated YM3711
      protein products clearly demonstrated that a large part of antibodies induced by
      YM3711 vaccination are directed at conformational epitopes of the Abeta complex
      and oligomers. Taken together, we demonstrate that YM3711 is a powerful DNA
      vaccine targeting a wide range of AD-related molecules and is worth examining in
      preclinical and clinical trials. 

PMID- 24086466
TI  - Genetic map construction and quantitative trait locus (QTL) detection of growth
      related traits in Litopenaeus vannamei for selective breeding applications.
AB  - Growth is a priority trait from the point of view of genetic improvement.
      Molecular markers linked to quantitative trait loci (QTL) have been regarded as
      useful for marker-assisted selection (MAS) in complex traits as growth. Using an
      intermediate F2 cross of slow and fast growth parents, a genetic linkage map of
      Pacific whiteleg shrimp, Litopenaeusvannamei, based on amplified fragment length
      polymorphisms (AFLP) and simple sequence repeats (SSR) markers was constructed.
      Meanwhile, QTL analysis was performed for growth-related traits. The linkage map
      consisted of 451 marker loci (429 AFLPs and 22 SSRs) which formed 49 linkage
      groups with an average marker space of 7.6 cM; they spanned a total length of
      3627.6 cM, covering 79.50% of estimated genome size. 14 QTLs were identified for
      growth-related traits, including three QTLs for body weight (BW), total length
      (TL) and partial carapace length (PCL), two QTLs for body length (BL), one QTL
      for first abdominal segment depth (FASD), third abdominal segment depth (TASD)
      and first abdominal segment width (FASW), which explained 2.62 to 61.42% of
      phenotypic variation. Moreover, comparison of linkage maps between L. vannamei
      and Penaeusjaponicus was applied, providing a new insight into the genetic base
      of QTL affecting the growth-related traits. The new results will be useful for
      conducting MAS breeding schemes in L. vannamei . 

PMID- 24086468
TI  - Dead end metabolites--defining the known unknowns of the E. coli metabolic
      network.
AB  - The EcoCyc database is an online scientific database which provides an integrated
      view of the metabolic and regulatory network of the bacterium Escherichia coli K
      12 and facilitates computational exploration of this important model organism. We
      have analysed the occurrence of dead end metabolites within the database--these
      are metabolites which lack the requisite reactions (either metabolic or
      transport) that would account for their production or consumption within the
      metabolic network. 127 dead end metabolites were identified from the 995
      compounds that are contained within the EcoCyc metabolic network. Their presence
      reflects either a deficit in our representation of the network or in our
      knowledge of E. coli metabolism. Extensive literature searches resulted in the
      addition of 38 transport reactions and 3 metabolic reactions to the database and
      led to an improved representation of the pathway for Vitamin B12 salvage. 39 dead
      end metabolites were identified as components of reactions that are not
      physiologically relevant to E. coli K-12--these reactions are properties of
      purified enzymes in vitro that would not be expected to occur in vivo. Our
      analysis led to improvements in the software that underpins the database and to
      the program that finds dead end metabolites within EcoCyc. The remaining dead end
      metabolites in the EcoCyc database likely represent deficiencies in our knowledge
      of E. coli metabolism.

PMID- 24086467
TI  - Structural and antigenic variation among diverse clade 2 H5N1 viruses.
AB  - Antigenic variation among circulating H5N1 highly pathogenic avian influenza A
      viruses mandates the continuous production of strain-specific pre-pandemic
      vaccine candidates and represents a significant challenge for pandemic
      preparedness. Here we assessed the structural, antigenic and receptor-binding
      properties of three H5N1 HPAI virus hemagglutinins, which were recently selected
      by the WHO as vaccine candidates [A/Egypt/N03072/2010 (Egypt10, clade 2.2.1),
      A/Hubei/1/2010 (Hubei10, clade 2.3.2.1) and A/Anhui/1/2005 (Anhui05, clade
      2.3.4)]. These analyses revealed that antigenic diversity among these three
      isolates was restricted to changes in the size and charge of amino acid side
      chains at a handful of positions, spatially equivalent to the antigenic sites
      identified in H1 subtype viruses circulating among humans. All three of the H5N1
      viruses analyzed in this study were responsible for fatal human infections, with
      the most recently-isolated strains, Hubei10 and Egypt10, containing multiple
      residues in the receptor-binding site of the HA, which were suspected to enhance
      mammalian transmission. However, glycan-binding analyses demonstrated a lack of
      binding to human alpha2-6-linked sialic acid receptor analogs for all three HAs,
      reinforcing the notion that receptor-binding specificity contributes only
      partially to transmissibility and pathogenesis of HPAI viruses and suggesting
      that changes in host specificity must be interpreted in the context of the host
      and environmental factors, as well as the virus as a whole. Together, our data
      reveal structural linkages with phylogenetic and antigenic analyses of recently
      emerged H5N1 virus clades and should assist in interpreting the significance of
      future changes in antigenic and receptor-binding properties. 

PMID- 24086469
TI  - A novel helper phage enabling construction of genome-scale ORF-enriched phage
      display libraries.
AB  - Phagemid-based expression of cloned genes fused to the gIIIP coding sequence and
      rescue using helper phages, such as VCSM13, has been used extensively for
      constructing large antibody phage display libraries. However, for randomly primed
      cDNA and gene fragment libraries, this system encounters reading frame problems
      wherein only one of 18 phages display the translated foreign peptide/protein
      fused to phagemid-encoded gIIIP. The elimination of phages carrying out-of-frame
      inserts is vital in order to improve the quality of phage display libraries. In
      this study, we designed a novel helper phage, AGM13, which carries trypsin
      sensitive sites within the linker regions of gIIIP. This renders the phage highly
      sensitive to trypsin digestion, which abolishes its infectivity. For open reading
      frame (ORF) selection, the phagemid-borne phages are rescued using AGM13, so that
      clones with in-frame inserts express fusion proteins with phagemid-encoded
      trypsin-resistant gIIIP, which becomes incorporated into the phages along with a
      few copies of AGM13-encoded trypsin-sensitive gIIIP. In contrast, clones with out
      of-frame inserts produce phages carrying only AGM13-encoded trypsin-sensitive
      gIIIP. Trypsin treatment of the phage population renders the phages with out-of
      frame inserts non-infectious, whereas phages carrying in-frame inserts remain
      fully infectious and can hence be enriched by infection. This strategy was
      applied efficiently at a genome scale to generate an ORF-enriched whole genome
      fragment library from Mycobacterium tuberculosis, in which nearly 100% of the
      clones carried in-frame inserts after selection. The ORF-enriched libraries were
      successfully used for identification of linear and conformational epitopes for
      monoclonal antibodies specific to mycobacterial proteins. 

PMID- 24086470
TI  - Evolutionary history of Indian Ocean nycteribiid bat flies mirroring the ecology
      of their hosts.
AB  - Bats and their parasites are increasingly investigated for their role in
      maintenance and transmission of potentially emerging pathogens. The islands of
      the western Indian Ocean hold nearly 50 bat species, mostly endemic and
      taxonomically well studied. However, investigation of associated viral,
      bacterial, and external parasites has lagged behind. In the case of their
      ectoparasites, more detailed information should provide insights into the
      evolutionary history of their hosts, as well as pathogen cycles in these wild
      animals. Here we investigate species of Nycteribiidae, a family of obligate
      hematophagous wingless flies parasitizing bats. Using morphological and molecular
      approaches, we describe fly species diversity sampled on Madagascar and the
      Comoros for two cave-roosting bat genera with contrasting ecologies: Miniopterus
      and Rousettus. Within the sampling area, 11 endemic species of insect-feeding
      Miniopterus occur, two of which are common to Madagascar and Comoros, while fruit
      consuming Rousettus are represented by one species endemic to each of these
      zones. Morphological and molecular characterization of flies reveals that
      nycteribiids associated with Miniopterus bats comprise three species largely
      shared by most host species. Flies of M. griveaudi, one of the two bats found on
      Madagascar and certain islands in the Comoros, belong to the same taxon, which
      accords with continued over-water population exchange of this bat species and the
      lack of inter-island genetic structuring. Flies parasitizing Rousettus belong to
      two distinct species, each associated with a single host species, again in
      accordance with the distribution of each endemic bat species. 

PMID- 24086471
TI  - Established thymic epithelial progenitor/stem cell-like cell lines differentiate
      into mature thymic epithelial cells and support T cell development.
AB  - Common thymic epithelial progenitor/stem cells (TEPCs) differentiate into
      cortical and medullary thymic epithelial cells (TECs), which are required for the
      development and selection of thymocytes. Mature TEC lines have been widely
      established. However, the establishment of TEPC lines is rarely reported. Here we
      describe the establishment of thymic epithelial stomal cell lines, named TSCs,
      from fetal thymus. TSCs express some of the markers present on tissue
      progenitor/stem cells such as Sca-1. Gene expression profiling verifies the
      thymic identity of TSCs. RANK stimulation of these cells induces expression of
      autoimmune regulator (Aire) and Aire-dependent tissue-restricted antigens (TRAs)
      in TSCs in vitro. TSCs could be differentiated into medullary thymic epithelial
      cell-like cells with exogenously expressed NF-kappaB subunits RelB and p52.
      Importantly, upon transplantation under the kidney capsules of nude mice, TSCs
      are able to differentiate into mature TEC-like cells that can support some
      limited development of T cells in vivo. These findings suggest that the TSC lines
      we established bear some characteristics of TEPC cells and are able to
      differentiate into functional TEC-like cells in vitro and in vivo. The cloned
      TEPC-like cell lines may provide useful tools to study the differentiation of
      mature TEC cells from precursors. 

PMID- 24086472
TI  - Development of a xeno-free autologous culture system for endothelial progenitor
      cells derived from human umbilical cord blood.
AB  - Despite promising preclinical outcomes in animal models, a number of challenges
      remain for human clinical use. In particular, expanding a large number of
      endothelial progenitor cells (EPCs) in vitro in the absence of animal-derived
      products is the most critical hurdle remaining to be overcome to ensure the
      safety and efficiency of human therapy. To develop in vitro culture conditions
      for EPCs derived from human cord blood (hCB-EPCs), we isolated extracts (UCE) and
      collagen (UC-collagen) from umbilical cord tissue to replace their animal-derived
      counterparts. UC-collagen and UCE efficiently supported the attachment and
      proliferation of hCB-EPCs in a manner comparable to that of animal-derived
      collagen in the conventional culture system. Our developed autologous culture
      system maintained the typical characteristics of hCB-EPCs, as represented by the
      expression of EPC-associated surface markers. In addition, the therapeutic
      potential of hCB-EPCs was confirmed when the transplantation of hCB-EPCs cultured
      in this autologous culture system promoted limb salvage in a mouse model of
      hindlimb ischemia and was shown to contribute to attenuating muscle degeneration
      and fibrosis. We suggest that the umbilical cord represents a source for
      autologous biomaterials for the in vitro culture of hCB-EPCs. The main
      characteristics and therapeutic potential of hCB-EPCs were not compromised in
      developed autologous culture system. The absence of animal-derived products in
      our newly developed in vitro culture removes concerns associated with secondary
      contamination. Thus, we hope that this culture system accelerates the realization
      of therapeutic applications of autologous hCB-EPCs for human vascular diseases. 

PMID- 24086474
TI  - Autistic traits in male and female students and individuals with high functioning
      autism spectrum disorders measured by the Polish version of the Autism-Spectrum
      Quotient.
AB  - So far no standardized screening instrument for autism spectrum disorders for
      adults has been developed in Poland. The main aim of the study was to explore the
      properties of the Polish version of the Autism-Spectrum Quotient (AQ), especially
      its reliability and discriminating power. The second purpose was to establish
      whether the pattern of sex and area of study differences in the amount of
      autistic traits found in other countries also exist in Poland. The groups in the
      study included students (n = 2819), adults with ASD (n = 60) and a non-clinical
      sample (n = 60) matched with the ASD group for age, sex, education and place of
      residence. The Polish version of AQ proved to be reliable, although--as in
      studies conducted in other countries--the internal consistency coefficients for
      subscales (with exception for social skill) were low. ASD diagnosis was the most
      powerful determinant of AQ scores. Sex differences in autistic traits and a
      relationship between autistic traits and area of study were found.

PMID- 24086473
TI  - The melanoma antigens MELOE-1 and MELOE-2 are translated from a bona fide
      polycistronic mRNA containing functional IRES sequences.
AB  - Our previous studies on melanoma antigens identified two new polypeptides, named
      MELOE-1 and MELOE-2, that are involved in immunosurveillance. Intriguingly, these
      antigens are coded by distinct open reading frames (ORF) of the meloe mRNA which
      is significantly expressed only in the melanocytic lineage. In addition, MELOE-1
      and -2 specific T cell clones recognized melanoma cells but very poorly normal
      melanocytes suggesting differential translation of meloe in normal vs tumor
      cells. This prompted us to elucidate the mechanisms of translation of these
      antigens in melanoma cells. We first demonstrated that no splicing event or
      cryptic promoter could generate shorter meloe transcripts containing only one of
      the two ORFs. Triggering meloe RNA degradation with a siRNA close to the ORF
      coding for MELOE-2 abrogated expression of both MELOE-1 and MELOE-2, thus
      confirming that the two ORFs are always associated. Next we showed, in a
      bicistronic reporter system, that IRES activities could be detected upstream of
      MELOE-1 and MELOE-2 and finally confirmed their translation from full length
      meloe cDNA in melanoma cells with eGFP constructs. In conclusion, meloe is a
      polycistronic mRNA that generates both MELOE-1 and MELOE-2 antigens through IRES
      dependent translation in melanoma cells and that may explain their tumor
      specificity. 

PMID- 24086475
TI  - Consistent surgeon evaluations of three-dimensional rendering of PET/CT scans of
      the abdomen of a patient with a ductal pancreatic mass.
AB  - Two-dimensional (2D) positron emission tomography (PET) and computed tomography
      (CT) are used for diagnosis and evaluation of cancer patients, requiring surgeons
      to look through multiple planar images to comprehend the tumor and surrounding
      tissues. We hypothesized that experienced surgeons would consistently evaluate
      three-dimensional (3D) presentation of CT images overlaid with PET images when
      preparing for a procedure. We recruited six Jefferson surgeons to evaluate the
      accuracy, usefulness, and applicability of 3D renderings of the organs
      surrounding a malignant pancreas prior to surgery. PET/CT and contrast-enhanced
      CT abdominal scans of a patient with a ductal pancreatic mass were segmented into
      3D surface renderings, followed by co-registration. Version A used only the
      PET/CT image, while version B used the contrast-enhanced CT scans co-registered
      with the PET images. The six surgeons answered 15 questions covering a) the ease
      of use and accuracy of models, b) how these models, with/without PET, changed
      their understanding of the tumor, and c) what are the best applications of the 3D
      visualization, on a scale of 1 to 5. The six evaluations revealed a statistically
      significant improvement from version A (score 3.6+/-0.5) to version B (score
      4.4+/-0.4). A paired-samples t-test yielded t(14) = -8.964, p<0.001. Across the
      surgeon cohort, contrast-enhanced CT fused with PET provided a more lifelike
      presentation than standard CT, increasing the usefulness of the presentation. The
      experienced surgeons consistently reported positive reactions to 3D surface
      renderings of fused PET and contrast-enhanced CT scans of a pancreatic cancer and
      surrounding organs. Thus, the 3D presentation could be a useful preparative tool
      for surgeons prior to making the first incision. This result supports proceeding
      to a larger surgeon cohort, viewing prospective 3D images from multiple types of
      cancer. 

PMID- 24086477
TI  - Gastropod seed dispersal: an invasive slug destroys far more seeds in its gut
      than native gastropods.
AB  - Seed dispersal is one of the most important mechanisms shaping biodiversity, and
      animals are one of the key dispersal vectors. Animal seed dispersal can directly
      or indirectly be altered by invasive organisms through the establishment of new
      or the disruption of existing seed dispersal interactions. So far it is known for
      a few gastropod species that they ingest and defecate viable plant seeds and
      consequently act as seed dispersers, referred to as gastropodochory. In a multi
      species experiment, consisting of five different plant species and four different
      gastropod species, we tested with a fully crossed design whether gastropodochory
      is a general mechanism across native gastropod species, and whether it is altered
      by the invasive alien slug species Arion lusitanicus. Specifically, we
      hypothesized that a) native gastropod species consume the seeds from all tested
      plant species in equal numbers (have no preference), b) the voracious invasive
      alien slug A. lusitanicus--similarly to its herbivore behaviour--consumes a
      higher amount of seeds than native gastropods, and that c) seed viability is
      equal among different gastropod species after gut passage. As expected all tested
      gastropod species consumed all tested plant species. Against our expectation
      there was a difference in the amount of consumed seeds, with the largest and
      native mollusk Helix pomatia consuming most seeds, followed by the invasive slug
      and the other gastropods. Seed damage and germination rates did not differ after
      gut passage through different native species, but seed damage was significantly
      higher after gut passage through the invasive slug A. lusitanicus, and their
      germination rates were significantly reduced.

PMID- 24086476
TI  - Tff3, as a novel peptide, regulates hepatic glucose metabolism.
AB  - Type 2 diabetes mellitus (T2DM) is a chronic metabolic disorder strongly
      associated with hepatic glucose intolerance and insulin resistance. The trefoil
      peptides are a family of small regulatory proteins and Tff3 is widely expressed
      in multiple tissues including liver. But the roles of Tff3 in regulation of
      glucose metabolism and insulin sensitivity in liver remain unclear. Here we show
      that the hepatic Tff3 expression levels were decreased in ob/ob and high-fat diet
      induced obese mice. Overexpression of Tff3 in primary mouse hepatocytes inhibited
      the expression of gluconeogenic genes, including G6pc, PEPCK and PGC-1alpha,
      subsequently decreasing cellular glucose output. GTT and ITT experiments revealed
      that adenovirus-mediated overexpression of Tff3 in diabetic or obese mice
      improved glucose tolerance and insulin sensitivity. Collectively, our results
      indicated that Tff3 peptides are involved in glucose homeostasis and insulin
      sensitivity, providing a promising peptide on new therapies against the metabolic
      disorders associated with T2DM. 

PMID- 24086478
TI  - English to Arabic translation of the Composite Abuse Scale (CAS): a multi-method
      approach.
AB  - BACKGROUND: The composite abuse scale (CAS) is a comprehensive tool used to
      measure intimate partner violence (IPV). The aim of the present study is to
      translate the CAS from English to Arabic. METHODS: The translation of the CAS was
      conducted in four stages using a multi-method approach: 1) preliminary forward
      translation, 2) discussion with a panel of bilingual experts, 3) focus groups
      discussion, and 4) back-translation of the CAS. The discussion included a
      linguistic validation by a comparison of the Arabic translation with the original
      English by assessing conceptual and content equivalence. FINDINGS: In all the
      stages of translation, there was an agreement to remove the question from the CAS
      that asked women about the use of objects in the vagina. Wording, format and
      order of the items were refined according to comments and suggestions made by the
      experts' panel and focus groups' members. The back-translated CAS showed similar
      wording and language of the original English version. CONCLUSIONS: The Arabic
      version of the CAS will help to measure the problem of IPV among Saudi women and
      possibly other Arabic-speaking women in future studies. This is important,
      particularly, in longitudinal studies or intervention studies among abused women
      and it allows a comparison of the results of studies from different cultures.
      However, further validations studies are needed to ensure accurate and equivalent
      Arabic translation of the CAS.

PMID- 24086479
TI  - Identification of new drug targets and resistance mechanisms in Mycobacterium
      tuberculosis.
AB  - Identification of new drug targets is vital for the advancement of drug discovery
      against Mycobacterium tuberculosis, especially given the increase of resistance
      worldwide to first- and second-line drugs. Because traditional target-based
      screening has largely proven unsuccessful for antibiotic discovery, we have
      developed a scalable platform for target identification in M. tuberculosis that
      is based on whole-cell screening, coupled with whole-genome sequencing of
      resistant mutants and recombineering to confirm. The method yields targets paired
      with whole-cell active compounds, which can serve as novel scaffolds for drug
      development, molecular tools for validation, and/or as ligands for co
      crystallization. It may also reveal other information about mechanisms of action,
      such as activation or efflux. Using this method, we identified resistance-linked
      genes for eight compounds with anti-tubercular activity. Four of the genes have
      previously been shown to be essential: AspS, aspartyl-tRNA synthetase, Pks13, a
      polyketide synthase involved in mycolic acid biosynthesis, MmpL3, a membrane
      transporter, and EccB3, a component of the ESX-3 type VII secretion system. AspS
      and Pks13 represent novel targets in protein translation and cell-wall
      biosynthesis. Both MmpL3 and EccB3 are involved in membrane transport. Pks13,
      AspS, and EccB3 represent novel candidates not targeted by existing TB drugs, and
      the availability of whole-cell active inhibitors greatly increases their
      potential for drug discovery. 

PMID- 24086480
TI  - Ultrastructural abnormalities in CA1 hippocampus caused by deletion of the actin
      regulator WAVE-1.
AB  - By conveying signals from the small GTPase family of proteins to the Arp2/3
      complex, proteins of the WAVE family facilitate actin remodeling. The WAVE-1
      isoform is expressed at high levels in brain, where it plays a role in normal
      synaptic processing, and is implicated in hippocampus-dependent memory retention.
      We used electron microscopy to determine whether synaptic structure is modified
      in the hippocampus of WAVE-1 knockout mice, focusing on the neuropil of CA1
      stratum radiatum. Mice lacking WAVE-1 exhibited alterations in the morphology of
      both axon terminals and dendritic spines; the relationship between the synaptic
      partners was also modified. The abnormal synaptic morphology we observed suggests
      that signaling through WAVE-1 plays a critical role in establishing normal
      synaptic architecture in the rodent hippocampus. 

PMID- 24086481
TI  - MiR-27a regulates apoptosis in nucleus pulposus cells by targeting PI3K.
AB  - The precise role of apoptosis in the pathogenesis of intervertebral disc
      degeneration (IDD) remains to be elucidated. We analyzed degenerative nucleus
      pulposus (NP) cells and found that the expression of miR-27a was increased. The
      overexpression of miR-27a was further verified using real-time RT-PCR.
      Bioinformatics target prediction identified phosphoinositide-3 kinases (PI3K) as
      putative targets of miR-27a. Furthermore, miR-27a inhibited PI3K expression by
      directly targeting their 3'-UTRs, and this inhibition was abolished by mutation
      of the miR-27a binding sites. Various cellular processes including cell growth,
      proliferation, migration and adhesion are regulated by activation of the PI3K/AKT
      signaling pathway, and nucleus pulposus cells are known to strongly express the
      phosphorylated survival protein AKT. Our results identify PI3K as a novel target
      of miR-27a. Upregulation of miR-27a thus targets PI3K, initiating apoptosis of
      nucleus pulposus cells. This present study revealed that downregulated miR-27a
      might develop a novel intervention for IDD treatment through the prevention of
      apoptosis in Nucleus pulposus Cells. 

PMID- 24086482
TI  - Hedgehog signaling regulates telomerase reverse transcriptase in human cancer
      cells.
AB  - The Hedgehog (HH) signaling pathway is critical for normal embryonic development,
      tissue patterning and cell differentiation. Aberrant HH signaling is involved in
      multiple human cancers. HH signaling involves a multi-protein cascade activating
      the GLI proteins that transcriptionally regulate HH target genes. We have
      previously reported that HH signaling is essential for human colon cancer cell
      survival and inhibition of this signal induces DNA damage and extensive cell
      death. Here we report that the HH/GLI axis regulates human telomerase reverse
      transcriptase (hTERT), which determines the replication potential of cancer
      cells. Suppression of GLI1/GLI2 functions by a C-terminus truncated GLI3
      repressor mutant (GLI3R), or by GANT61, a pharmacological inhibitor of GLI1/GLI2,
      reduced hTERT protein expression in human colon cancer, prostate cancer and
      Glioblastoma multiforme (GBM) cell lines. Expression of an N-terminus deleted
      constitutively active mutant of GLI2 (GLI2DeltaN) increased hTERT mRNA and
      protein expression and hTERT promoter driven luciferase activity in human colon
      cancer cells while GANT61 inhibited hTERT mRNA expression and hTERT promoter
      driven luciferase activity. Chromatin immunoprecipitation with GLI1 or GLI2
      antibodies precipitated fragments of the hTERT promoter in human colon cancer
      cells, which was reduced upon exposure to GANT61. In contrast, expression of GLI1
      or GLI2DeltaN in non-malignant 293T cells failed to alter the levels of hTERT
      mRNA and protein, or hTERT promoter driven luciferase activity. Further,
      expression of GLI2DeltaN increased the telomerase enzyme activity, which was
      reduced by GANT61 administration in human colon cancer, prostate cancer, and GBM
      cells. These results identify hTERT as a direct target of the HH signaling
      pathway, and reveal a previously unknown role of the HH/GLI axis in regulating
      the replication potential of cancer cells. These findings are of significance in
      understanding the important regulatory mechanisms that determine the functions of
      HH/GLI signaling in cancer cells. 

PMID- 24086483
TI  - Identification of the mRNA expression status of the dopamine D2 receptor and
      dopamine transporter in peripheral blood lymphocytes of schizophrenia patients.
AB  - The aim of this study was to detect the mRNA expression levels of the dopamine D2
      receptor (DRD2) and dopamine transporter (DAT) in peripheral blood leukocytes
      (PBLs) of schizophrenia patients and to explore the relationship between the mRNA
      expression levels and the clinical symptoms of schizophrenia. The research
      included 25 cases of acute schizophrenia patients, 27 cases of chronic
      schizophrenia patients, and 30 healthy controls. In every case, we measured the
      mRNA levels of DRD2 and DAT in PBLs by real-time quantitative reverse
      transcription-polymerase chain reaction (real-time RT-PCR), and we evaluated the
      patients' clinical symptoms using the Positive and Negative Syndrome Scale
      (PANSS). DRD2 mRNA levels in PBLs of acute schizophrenia patients, chronic
      schizophrenia patients, and healthy controls were 0.32+/-0.13, 0.37+/-0.19, and
      0.34+/-0.09, respectively, and the difference was not significant. DAT mRNA
      levels in PBLs of the abovementioned groups were 0.48+/-0.24, 0.58+/-0.21 and
      0.39+/-0.24, respectively (F = 4.330, P = 0.017), and comparisons between every
      group showed that DAT mRNA levels in PBLs of chronic schizophrenia patients were
      significantly higher than those in healthy controls (MS interclass = 0.198, p =
      0.005). The correlation between DRD2 mRNA levels in PBLs and the positive symptom
      points of PANSS in acute schizophrenia patients was significant (r = 0.443, p =
      0.044). In conclusion, DRD2 mRNA levels in PBLs are correlated with positive
      symptoms in acute schizophrenia patients, and DAT mRNA levels in PBLs of chronic
      schizophrenia patients are over-expressed. 

PMID- 24086484
TI  - Myopic shift and outdoor activity among primary school children: one-year follow
      up study in Beijing.
AB  - PURPOSE: To assess whether a change in myopia related oculometric parameters of
      primary school children in Beijing was associated with indoors and outdoors
      activity. METHODS: The longitudinal school-based study included school children
      who were examined in 2011 and who were re-examined in 2012. The children
      underwent a comprehensive eye examination including ocular biometry by optical
      low-coherence reflectometry and non-cycloplegic refractometry. Parents and
      children had a detailed interview including questions on time spent indoors and
      outdoors. RESULTS: Out of 681 students examined at baseline, 643 (94.4%) returned
      for follow-up examination. Within the one-year period, mean time spent daily
      outdoors increased by 0.4+/-0.9 hours, mean axial length by 0.26+/-0.49 mm, the
      ratio of axial length divided by anterior corneal curvature (AL/CC) by 0.03+/
      0.06, and myopic refractive error by -0.06+/-0.89 diopters. In multivariate
      analysis, elongation of axial length was significantly associated with less total
      time spent outdoors (P = 0.02; standardized coefficient beta -0.12) and more time
      spent indoors with studying (P = 0.007; beta: 0.14) after adjustment for maternal
      myopia (P = 0.02; beta: 0.12). An increase in AL/CC was significantly associated
      with less time spent outdoors (P = 0.01; beta:-0.12) after adjustment for
      paternal myopia (P = 0.003; beta: 0.15) and if region of habitation was
      excludedors for leisure (P = 0.006; beta:-0.13), with less total time spent
      outdoors (P = 0.04; beta:-0.10), or with more time spent i. An increase in myopic
      refractive error, after adjustment for age, was significantly associated with
      less time spent outdo ndoors with studying (P = 0.005; beta: 0.13). CONCLUSIONS:
      A change in oculometric parameters indicating an increase in myopia was
      significantly associated with less time spent outdoors and more time spent
      indoors in school children in Greater Beijing within a study period of one year.
      Our study provides additional information on the potentially helpful role of
      outdoors activity in the prevention of myopia. Public health care measures such
      as school agendas may potentially take it into account.

PMID- 24086485
TI  - Levels, trends and disparities in public-health-related indicators among
      reproductive-age women in Bangladesh by urban-rural and richest-poorest groups,
      1993-2011.
AB  - BACKGROUND AND OBJECTIVES: Although Bangladesh has already achieved noticeable
      progress in the field of development and health, disparities in public health
      indicators for several markers are still reported. To assess public health
      development in Bangladesh during the last two decades, firstly, we analysed
      levels, trends and disparities in public-health-related indicators by rural
      versus urban as well as by the richest versus poorest group of women who have
      ever been married. Secondly, using the most recent data set we performed multiple
      analyses to check whether urban-rural and richest-poorest disparities were still
      significant. METHODS: The analysis was based on six nationally representative
      data sets from the Bangladesh Demographic and Health Surveys (BDHS) conducted in
      1993-94 (n=9,640), 1996-1997 (n=9,127), 1999-2000 (n=10,544), 2004 (n=11,440),
      2007 (n=10,996) and 2011 (n=17,749). The outcome variables were six selected
      public-health-related indicators. We performed various types of analyses,
      including multiple logistic regressions. RESULTS: The trend of all indicators
      except being overweight (1993-2011) displayed gradual improvements for both
      markers. However, the urban and richest groups revealed a better situation than
      their counterparts in both simple and multiple analyses. Disparities between
      richest-poorest groups were more pronounced than urban-rural disparities. For
      instance, the prevalence of delivery at any healthcare facility in 2011 was 20.4%
      in rural areas and 46.5% in urban areas, whereas it was 9.1% in the poorest group
      and 57.6% in the richest group. CONCLUSION: The public health sector in
      Bangladesh has achieved some successes over the last two decades. However, urban
      rural and richest-poorest disparities are still considerable and therefore more
      public health strategies and efforts are clearly needed for the rural and poorest
      groups of women in order to reduce these gaps further.

PMID- 24086486
TI  - Prevalence of dural ectasia in Loeys-Dietz syndrome: comparison with Marfan
      syndrome and normal controls.
AB  - BACKGROUND AND PURPOSE: Dural ectasia is well recognized in Marfan syndrome (MFS)
      as one of the major diagnostic criteria, but the exact prevalence of dural
      ectasia is still unknown in Loeys-Dietz syndrome (LDS), which is a recently
      discovered connective tissue disease. In this study, we evaluated the prevalence
      of dural ectasia in LDS according by using qualitative and quantitative methods
      and compared our findings with those for with MFS and normal controls. MATERIAL
      AND METHODS: We retrospectively studied 10 LDS (6 males, 4 females, mean age 36.3
      years) and 20 MFS cases (12 males, 8 females, mean age 37.1 years) and 20
      controls (12 males, 8 females, mean age 36.1 years) both qualitatively and
      quantitatively using axial CT images and sagittal multi-planar reconstruction
      images of the lumbosacral region. For quantitative examination, we adopted two
      methods: method-1 (anteroposterior dural diameter of S1> L4) and method-2 (ratio
      of anteroposterior dural diameter/vertebral body diameter>cutoff values). The
      prevalence of dural ectasia among groups was compared by using Fisher's exact
      test and the Tukey-Kramer test. RESULTS: In LDS patients, the qualitative method
      showed 40% of dural ectasia, the quantitative method-1 50%, and the method-2 70%.
      In MFS patients, the corresponding prevalences were 50%, 75%, and 85%, and in
      controls, 0%, 0%, and 5%. Both LDS and MFS had a significantly wider dura than
      controls. CONCLUSIONS: While the prevalence of dural ectasia varied depending on
      differences in qualitative and quantitative methods, LDS as well as MFS, showed,
      regardless of method, a higher prevalence of dural ectasia than controls. This
      finding should help the differentiation of LDS from controls.

PMID- 24086487
TI  - Immunogenic properties of Streptococcus agalactiae FbsA fragments.
AB  - Several species of Gram-positive bacteria can avidly bind soluble and surface
      associated fibrinogen (Fng), a property that is considered important in the
      pathogenesis of human infections. To gain insights into the mechanism by which
      group B Streptococcus (GBS), a frequent neonatal pathogen, interacts with Fng, we
      have screened two phage displayed genomic GBS libraries. All of the Fng-binding
      phage clones contained inserts encoding fragments of FbsA, a protein displaying
      multiple repeats. Since the functional role of this protein is only partially
      understood, representative fragments were recombinantly expressed and analyzed
      for Fng binding affinity and ability to induce immune protection against GBS
      infection. Maternal immunization with 6pGST, a fragment containing five repeats,
      significantly protected mouse pups against lethal GBS challenge and these
      protective effects could be recapitulated by administration of anti-6pGST serum
      from adult animals. Notably, a monoclonal antibody that was capable of
      neutralizing Fng binding by 6pGST, but not a non-neutralizing antibody, could
      significantly protect pups against lethal GBS challenge. These data suggest that
      FbsA-Fng interaction promotes GBS pathogenesis and that blocking such interaction
      is a viable strategy to prevent or treat GBS infections. 

PMID- 24086488
TI  - Molecular epidemiology and clinical characteristics of hepatitis B identified
      through the French mandatory notification system.
AB  - BACKGROUND & AIMS: Strains responsible for acute hepatitis B infections (AHB) in
      France have not been characterized. This study was first designed to analyze the
      molecular epidemiology of AHB and second to describe the differences between AHB
      and chronic hepatitis B (CHB) exacerbations. METHODS: This prospective study was
      based on the French mandatory notification system for AHB. 147 samples
      corresponding to declared cases were shipped to a central laboratory for
      classification as AHB or CHB according to the level of anti-HBc IgM and anti-HBc
      avidity. RESULTS: Based on biological marker values and file examination, 75
      cases (59%) were classified as AHB. Independently of the acute or chronic status,
      genotype A (57%), D (22%) and E (14%) were the most prevalent and no phylogenetic
      clustering was observed among HBV sequences (n=68). Precore or basal core
      promoter variants were not particularly associated with disease severity but were
      more prevalent in CHB. No antiviral resistant strains or immune-escape HBsAg was
      observed. HBV viral loads in AHB or CHB were comparable but with opposite
      distributions. ALT levels reached 10 times the upper normal value in 94% of AHB
      but only in 24% of CHB. CONCLUSIONS: After rigorous classification, no major
      difference at the genetic level was found between HBV strains isolated from AHB
      and CHB. Absence of potentially deleterious variant detection is reassuring. When
      based upon HBsAg and anti-HBc IgM determination, AHB notification may falsely
      include more than 40% CHB, leading to an important risk of bias in national
      surveillance programs of AHB.

PMID- 24086489
TI  - A transcript profiling approach reveals an abscisic acid-specific
      glycosyltransferase (UGT73C14) induced in developing fiber of Ligon lintless-2
      mutant of cotton (Gossypium hirsutum L.).
AB  - Ligon lintless-2, a monogenic dominant cotton (Gossypium hirsutum L.) fiber
      mutation, causing extreme reduction in lint fiber length with no pleiotropic
      effects on vegetative growth, represents an excellent model system to study fiber
      elongation. A UDP-glycosyltransferase that was highly expressed in developing
      fibers of the mutant Ligon lintless-2 was isolated. The predicted amino acid
      sequence showed ~53% similarity with Arabidopsis UGT73C sub-family members and
      the UDP-glycosyltransferase was designated as UGT73C14. When expressed in
      Escherichia coli as a recombinant protein with a maltose binding protein tag,
      UGT73C14 displayed enzymatic activity toward ABA and utilized UDP-glucose and UDP
      galactose as the sugar donors. The recombinant UGT73C14 converted natural
      occurring isoform (+)-cis, trans-ABA better than (+)-trans, trans-ABA and (-)
      cis, trans-ABA. Transgenic Arabidopsis plants constitutively overexpressing
      UGT73C14 did not show phenotypic changes under standard growth conditions.
      However, the increased glycosylation of ABA resulted in phenotypic changes in
      post-germinative growth and seedling establishment, confirming in vivo activity
      of UGT73C14 for ABA. This suggests that the expression level of UGT73C14 is
      regulated by the observed elevated levels of ABA in developing fibers of the Li 2
      mutant line and may be involved in the regulation of ABA homeostasis. 

PMID- 24086491
TI  - Differential active site loop conformations mediate promiscuous activities in the
      lactonase SsoPox.
AB  - Enzymes are proficient catalysts that enable fast rates of Michaelis-complex
      formation, the chemical step and products release. These different steps may
      require different conformational states of the active site that have distinct
      binding properties. Moreover, the conformational flexibility of the active site
      mediates alternative, promiscuous functions. Here we focused on the lactonase
      SsoPox from Sulfolobus solfataricus. SsoPox is a native lactonase endowed with
      promiscuous phosphotriesterase activity. We identified a position in the active
      site loop (W263) that governs its flexibility, and thereby affects the substrate
      specificity of the enzyme. We isolated two different sets of substitutions at
      position 263 that induce two distinct conformational sampling of the active loop
      and characterized the structural and kinetic effects of these substitutions.
      These sets of mutations selectively and distinctly mediate the improvement of the
      promiscuous phosphotriesterase and oxo-lactonase activities of SsoPox by
      increasing active-site loop flexibility. These observations corroborate the idea
      that conformational diversity governs enzymatic promiscuity and is a key feature
      of protein evolvability. 

PMID- 24086490
TI  - Disrupting the oncogenic synergism between nucleolin and Ras results in cell
      growth inhibition and cell death.
AB  - BACKGROUND: The ErbB receptors, Ras proteins and nucleolin are major contributors
      to malignant transformation. The pleiotropic protein nucleolin can bind to both
      Ras protein and ErbB receptors. Previously, we have demonstrated a crosstalk
      between Ras, nucleolin and the ErbB1 receptor. Activated Ras facilitates
      nucleolin interaction with ErbB1 and stabilizes ErbB1 levels. The three oncogenes
      synergistically facilitate anchorage independent growth and tumor growth in nude
      mice. METHODOLOGY/PRINCIPAL FINDINGS: In the present study we used several cancer
      cell lines. The effect of Ras and nucleolin inhibition was determined using cell
      growth, cell death and cell motility assays. Protein expression was determined by
      immunohistochemistry. We found that inhibition of Ras and nucleolin reduces tumor
      cell growth, enhances cell death and inhibits anchorage independent growth. Our
      results reveal that the combined treatment affects Ras and nucleolin levels and
      localization. Our study also indicates that Salirasib (FTS, Ras inhibitor)
      reduces cell motility, which is not affected by the nucleolin inhibitor.
      CONCLUSIONS/SIGNIFICANCE: These results suggest that targeting both nucleolin and
      Ras may represent an additional avenue for inhibiting cancers driven by these
      oncogenes.

PMID- 24086492
TI  - Detection of an extended human volatome with comprehensive two-dimensional gas
      chromatography time-of-flight mass spectrometry.
AB  - BACKGROUND: Comprehensive two-dimensional gas chromatography coupled with time-of
      flight mass spectrometry (GCxGC-TOF MS) has been proposed as a powerful new tool
      for multidimensional analysis of complex chemical mixtures. We investigated GCxGC
      TOF MS as a new method for identifying volatile organic compounds (VOCs) in
      normal human breath. METHODS: Samples of alveolar breath VOCs and ambient room
      air VOC were collected with a breath collection apparatus (BCA) onto separate
      sorbent traps from 34 normal healthy volunteers (mean age = 40 yr, SD = 17 yr,
      male/female = 19/15). VOCs were separated on two serial capillary columns
      separated by a cryogenic modulator, and detected with TOF MS. The first and
      second dimension columns were non-polar and polar respectively. RESULTS: BCA
      collection combined with GC*GC-TOF MS analysis identified approximately 2000
      different VOCs in samples of human breath, many of which have not been previously
      reported. The 50 VOCs with the highest alveolar gradients (abundance in breath
      minus abundance in ambient room air) mostly comprised benzene derivatives,
      acetone, methylated derivatives of alkanes, and isoprene. CONCLUSIONS: Collection
      and analysis of breath VOCs with the BCA-GC*GC-TOF MS system extended the size of
      the detectable human volatile metabolome, the volatome, by an order of magnitude
      compared to previous reports employing one-dimensional GC-MS. The size of the
      human volatome has been under-estimated in the past due to coelution of VOCs in
      one-dimensional GC analytical systems.

PMID- 24086493
TI  - Cuticular membrane of Fuyu persimmon fruit is strengthened by triterpenoid nano
      fillers.
AB  - The mechanical defensive performance of fruit cuticular membranes (CMs) is
      largely dependent on the molecular arrangement of their constituents. Here, we
      elucidated nano-sized interactions between cutin and triterpenoids in the
      cuticular matrix of Fuyu persimmon fruits (Diospyroskaki Thunb. cv. Fuyu),
      focusing on the mechanical properties using a combination of polymer analyses.
      The fruit CMs of Fuyu were primarily composed of wax (34.7%), which was
      predominantly triterpenoids followed by higher aliphatic compounds, and cutin
      (48.4%), primarily consisting of 9,10-epoxy-18-hydroxyoctadecanoic acid and
      9,10,18-trihydroxyoctadecanoic acid. Based on the tensile tests of the CM, the
      removal of wax lead to a considerable decrease in the maximum stress and elastic
      modulus accompanied by an increase in the maximum strain, indicating that wax is
      of significant importance for maintaining the mechanical strength of the CM. Wide
      angle X-ray diffraction and relaxation time measurements using solid-state (13)C
      nuclear magnetic resonance indicated that the triterpenoids in the cuticular
      matrix construct a nanocomposite at a mixing scale below 20-24 nm; however, the
      higher aliphatic compounds did not exhibit clear interactions with cutin. The
      results indicated that the triterpenoids in the cuticular matrix endow toughness
      to the CM by functioning as a nanofiller. 

PMID- 24086494
TI  - Protein kinase CK2 inhibition down modulates the NF-kappaB and STAT3 survival
      pathways, enhances the cellular proteotoxic stress and synergistically boosts the
      cytotoxic effect of bortezomib on multiple myeloma and mantle cell lymphoma
      cells.
AB  - CK2 is a pivotal pro-survival protein kinase in multiple myeloma that may likely
      impinge on bortezomib-regulated cellular pathways. In the present study, we
      investigated CK2 expression in multiple myeloma and mantle cell lymphoma, two
      bortezomib-responsive B cell tumors, as well as its involvement in bortezomib
      induced cytotoxicity and signaling cascades potentially mediating bortezomib
      resistance. In both tumors, CK2 expression correlated with that of its activated
      targets NF-kappaB and STAT3 transcription factors. Bortezomib-induced
      proliferation arrest and apoptosis were significantly amplified by the
      simultaneous inhibition of CK2 with two inhibitors (CX-4945 and K27) in multiple
      myeloma and mantle cell lymphoma cell lines, in a model of multiple myeloma bone
      marrow microenvironment and in cells isolated from patients. CK2 inhibition
      empowered bortezomib-triggered mitochondrial-dependent cell death.
      Phosphorylation of NF-kappaB p65 on Ser529 (a CK2 target site) and rise of the
      levels of the endoplasmic reticulum stress kinase/endoribonuclease Ire1alpha were
      markedly reduced upon CK2 inhibition, as were STAT3 phospho Ser727 levels. On the
      contrary, CK2 inhibition increased phospho Ser51 eIF2alpha levels and enhanced
      the bortezomib-dependent accumulation of poly-ubiquitylated proteins and of the
      proteotoxic stress-associated chaperone Hsp70. Our data suggest that CK2 over
      expression in multiple myeloma and mantle cell lymphoma cells might sustain
      survival signaling cascades and can antagonize bortezomib-induced apoptosis at
      different levels. CK2 inhibitors could be useful in bortezomib-based combination
      therapies. 

PMID- 24086495
TI  - Extracellular signal-regulated kinase 1/2 signaling pathway is required for
      endometrial decidualization in mice and human.
AB  - Decidualization is a crucial change required for successful embryo implantation
      and the maintenance of pregnancy. During this process, endometrial stromal cells
      differentiate into decidual cells in response to the ovarian steroid hormones of
      early pregnancy. Extracellular signal-regulated protein kinases 1 and 2 (ERK1/2)
      are known to regulate cell proliferation and apoptosis in multiple cell types,
      including uterine endometrial cells. Aberrant activation of ERK1/2 has recently
      been implicated in the pathological processes of endometriosis and endometrial
      cancer. However, the function of ERK1/2 signaling during implantation and
      decidualization is still unknown. To determine the role and regulation of ERK1/2
      signaling during implantation and decidualization, we examine ERK1/2 signaling in
      the mouse uterus during early pregnancy using immunostaining and qPCR.
      Interestingly, levels of phospho-ERK1/2 were highest within decidual cells
      located at the implantation sites. Expression levels of ERK1/2 target genes were
      also significantly higher at implantation sites, when compared to either inter
      implantation sites. To determine if ERK1/2 signaling is also important during
      human endometrial decidualization, we examined levels of phospho-ERK1/2 in
      cultured human endometrial stromal cells during in vitro decidualization.
      Following treatment with a well-established decidualization-inducing
      steroidogenic cocktail, levels of phospho-ERK1/2 were markedly increased.
      Treatment with the ERK1/2 inhibitor, U0126, significantly decreased the
      expression of the known decidualization marker genes, IGFBP1 and PRL as well as
      inhibited the induction of known ERK1/2 target genes; FOS, MSK1, STAT1, and
      STAT3. Interestingly, the phosphorylation level of CCAAT/ enhancer binding
      protein beta (C/EBPbeta), a protein previously shown to be critical for
      decidualization, was significantly reduced in this model. These results suggest
      that ERK1/2 signaling is required for successful decidualization in mice as well
      as human endometrial stromal cells and implicates C/EBPbeta as a downstream
      target of ERK1/2. 

PMID- 24086496
TI  - Genetic variants of coagulation factor XI show association with ischemic stroke
      up to 70 years of age.
AB  - BACKGROUND AND PURPOSE: Coagulation factor XI (FXI) has an important role in the
      propagation and stabilization of a thrombus upon vessel injury. High FXI levels
      have been implicated in thrombotic diseases including ischemic stroke. The aim of
      our study was to investigate whether FXI gene (F11) variants are associated with
      ischemic stroke. METHODS: The discovery sample, the Sahlgrenska Academy Study on
      Ischemic Stroke (SAHLSIS), included 844 patients with ischemic stroke and 668
      controls, all aged 18-70 years. Replication was performed in the Lund Stroke
      Register (LSR) and Malmo Diet and Cancer study (MDC), together including 1213
      patients and 788 controls up to 70 years of age, and in total 3145 patients and
      1793 controls (18-102 years). Seven F11 single-nucleotide polymorphisms (SNPs)
      were selected using a tagging approach. RESULTS: The SNPs rs3733403, rs925451,
      and rs1593 showed independent associations with overall ischemic stroke in
      SAHLSIS, ORs of 0.74 (95% CI 0.59-0.94), 1.24 (95% CI 1.06-1.46), and 0.70 (95%
      CI 0.55-0.90), respectively. The association for rs925451 was replicated in the
      LSR and MDC sample in a pre-specified analysis of subjects aged 70 years or
      younger, OR of 1.16 (95% CI 1.00-1.34), whereas no SNP was replicated when all
      ages were included. In line with this, one F11 haplotype was associated with
      overall ischemic stroke in the discovery sample and in the replication sample
      <=70 years. CONCLUSIONS: We found significant associations between F11 variation
      and overall ischemic stroke up to 70 years of age. These findings motivate
      further studies on the role of F11 in ischemic stroke, especially in younger
      individuals.

PMID- 24086497
TI  - Upregulation of tissue factor by activated Stat3 contributes to malignant pleural
      effusion generation via enhancing tumor metastasis and vascular permeability in
      lung adenocarcinoma.
AB  - Malignant pleural effusion (MPE) is a poor prognostic sign for patients with lung
      cancer. Tissue factor (TF) is a coagulation factor that participates in
      angiogenesis and vascular permeability and is abundant in MPE. We previously
      demonstrated that autocrine IL-6-activated Stat3 contributes to tumor metastasis
      and upregulation of VEGF, resulting in the generation of MPE in lung
      adenocarcinoma. In this study, we found IL-6-triggered Stat3 activation also
      induces TF expression. By using pharmacologic inhibitors, it was shown that JAK2
      kinase, but not Src kinase, contributed to autocrine IL-6-induced TF expression.
      Inhibition of Stat3 activation by dominant negative Stat3 (S3D) in lung
      adenocarcinoma suppressed TF-induced coagulation, anchorage-independent growth in
      vitro, and tumor growth in vivo. Consistently, knockdown of TF expression by
      siRNA resulted in a reduction of anchorage-independent growth of lung
      adenocarcinoma cells. Inhibition of TF expression also decreased the adhesion
      ability of cancer cells in normal lung tissues. In the nude mouse model, both
      lung metastasis and MPE generation were decreased when PC14PE6/AS2-siTF cells (TF
      expression was silenced) were intravenously injected. PC14PE6/AS2-siTF cells also
      produced less malignant ascites through inhibition of vascular permeability. In
      summary, we showed that TF expression plays a pivotal role in the pathogenesis of
      MPE generation via regulating of tumor metastasis and vascular permeability in
      lung adenocarcinoma bearing activated Stat3. 

PMID- 24086498
TI  - Coordinated and interactive expression of genes of lipid metabolism and
      inflammation in adipose tissue and liver during metabolic overload.
AB  - BACKGROUND: Chronic metabolic overload results in lipid accumulation and
      subsequent inflammation in white adipose tissue (WAT), often accompanied by non
      alcoholic fatty liver disease (NAFLD). In response to metabolic overload, the
      expression of genes involved in lipid metabolism and inflammatory processes is
      adapted. However, it still remains unknown how these adaptations in gene
      expression in expanding WAT and liver are orchestrated and whether they are
      interrelated. METHODOLOGY/PRINCIPAL FINDINGS: ApoE*3Leiden mice were fed HFD or
      chow for different periods up to 12 weeks. Gene expression in WAT and liver over
      time was evaluated by micro-array analysis. WAT hypertrophy and inflammation were
      analyzed histologically. Bayesian hierarchical cluster analysis of dynamic WAT
      gene expression identified groups of genes ('clusters') with comparable
      expression patterns over time. HFD evoked an immediate response of five clusters
      of 'lipid metabolism' genes in WAT, which did not further change thereafter. At a
      later time point (>6 weeks), inflammatory clusters were induced. Promoter
      analysis of clustered genes resulted in specific key regulators which may
      orchestrate the metabolic and inflammatory responses in WAT. Some master
      regulators played a dual role in control of metabolism and inflammation. When WAT
      inflammation developed (>6 weeks), genes of lipid metabolism and inflammation
      were also affected in corresponding livers. These hepatic gene expression changes
      and the underlying transcriptional responses in particular, were remarkably
      similar to those detected in WAT. CONCLUSION: In WAT, metabolic overload induced
      an immediate, stable response on clusters of lipid metabolism genes and induced
      inflammatory genes later in time. Both processes may be controlled and
      interlinked by specific transcriptional regulators. When WAT inflammation began,
      the hepatic response to HFD resembled that in WAT. In all, WAT and liver respond
      to metabolic overload by adaptations in expression of gene clusters that control
      lipid metabolism and inflammatory processes in an orchestrated and interrelated
      manner.

PMID- 24086499
TI  - Plant tissues in 3D via X-ray tomography: simple contrasting methods allow high
      resolution imaging.
AB  - Computed tomography remains strongly underused in plant sciences despite its high
      potential in delivering detailed 3D phenotypical information because of the low X
      ray absorption of most plant tissues. Existing protocols to study soft tissues
      display poor performance, especially when compared to those used on animals. More
      efficient protocols to study plant material are therefore needed. Flowers of
      Arabidopsis thaliana and Marcgravia caudata were immersed in a selection of
      contrasting agents used to treat samples for transmission electron microscopy.
      Grayscale values for floral tissues and background were measured as a function of
      time. Contrast was quantified via a contrast index. The thick buds of Marcgravia
      were scanned to determine which contrasting agents best penetrate thick tissues.
      The highest contrast increase with cytoplasm-rich tissues was obtained with
      phosphotungstate, whereas osmium tetroxide and bismuth tatrate displayed the
      highest contrast increase with vacuolated tissues. Phosphotungstate also
      displayed the best sample penetration. Furthermore, infiltration with
      phosphotungstate allowed imaging of all plants parts at a high resolution of 3
      um, which approaches the maximum resolution of our equipment: 1.5 um. The high
      affinity of phosphotungstate for vasculature, cytoplasm-rich tissue, and pollen
      causes these tissues to absorb more X-rays than the surrounding tissues, which,
      in turn, makes these tissues appear brighter on the scan data. Tissues with
      different brightness can then be virtually dissected from each other by selecting
      the bracket of grayscale to be visualized. Promising directions for the future
      include in silico phenotyping and developmental studies of plant inner parts
      (e.g., ovules, vasculature, pollen, and cell nuclei) via virtual dissection as
      well as correlations of quantitative phenotypes with omics datasets. Therefore,
      this work represents a crucial improvement of previous methods, allowing new
      directions of research to be undertaken in areas ranging from morphology to
      systems biology. 

PMID- 24086500
TI  - First parent-child meetings in international adoptions: a qualitative study.
AB  - International adoptions involve approximately 30,000 children worldwide each
      year. Nearly all of the adoptive parents travel to the child's country of birth
      to meet them and bring them home. The objective of this study is to analyze the
      adoptive parents' account of their first meetings with their child. The study
      includes 46 parents who adopted one or more children internationally. Each parent
      participated in a semi-structured interview, focused on these first parent-child
      meetings. The interviews were analyzed according to a qualitative
      phenomenological method, Interpretative Phenomenological Analysis. The principal
      themes that emerged from the analysis of the interviews were: the scene when the
      child is entrusted to the parents, the discovery of the child's body, and the
      first parent-child interaction. Within these three principal themes, several
      subthemes dealt with difficult experiences: moments of solitude and anxiety,
      shocking images of the children's living conditions, lack of preparation and of
      information about the child, poor health, parental reactions of rejection, worry
      about the child's body, aggressive reactions by the child, worry about the
      child's reactions, and contrast with the expected interaction. Thirty-two
      interviews included at least one of these subthemes. At the structural level of
      the discourse; the characteristics of 33 interviews are those described in the
      literature as significantly more frequent in traumatized than in non-traumatized
      subjects. These results raise questions about the consequences of difficult,
      possibly traumatic experiences, at the moment of meeting the child, and they
      underline the need for work on preparation and prevention before the parents
      leave on their journey.

PMID- 24086501
TI  - Identifying adolescent sleep problems.
AB  - OBJECTIVES: To examine the efficacy of self-report and parental report of
      adolescent sleep problems and compare these findings to the incidence of
      adolescents who fulfill clinical criteria for a sleep problem. Sleep and daytime
      functioning factors that predict adolescents' self-identification of a sleep
      problem will also be examined. METHOD: 308 adolescents (aged 13-17 years) from
      eight socioeconomically diverse South Australian high schools participated in
      this study. Participants completed a survey battery during class time, followed
      by a 7-day Sleep Diary and the Flinders Fatigue Scale completed on the final day
      of the study. Parents completed a Sleep, Medical, Education and Family History
      Survey. RESULTS: The percentage of adolescents fulfilling one or more of the
      criteria for a sleep problem was inordinately high at 66%. Adolescent self
      reporting a sleep problem was significantly lower than the adolescents who had
      one or more of the clinical criteria for a sleep problem (23.1% vs. 66.6%; chi(2)
      = 17.46, p<.001). Parental report of their adolescent having a sleep problem was
      significantly lower than adolescent self-report (14.3% vs. 21.1%, p<.001).
      Adolescents who reported unrefreshing sleep were 4.81 times more likely to report
      a sleep problem. For every hour that bedtime was delayed, the odds of self
      reporting a sleep problem increased by 1.91 times, while each additional 10
      minutes taken to fall asleep increased the odds 1.40 times. CONCLUSION: While
      many adolescents were found to have sleep patterns indicative of a sleep problem,
      only a third of this number self-identify having a sleep problem, while only a
      sixth of this number are indicated by parental report. This study highlights
      important features to target in future sleep education and intervention
      strategies for both adolescents and parents.

PMID- 24086503
TI  - Which T category of nasopharyngeal carcinoma may benefit most from volumetric
      modulated arc therapy compared with step and shoot intensity modulated radiation
      therapy.
AB  - BACKGROUND: To compare volumetric modulated arc therapy (VMAT) with conventional
      step and shoot intensity modulated radiation therapy (s-IMRT) in nasopharyngeal
      carcinoma (NPC) patients, and identify which T category patient gains the maximum
      benefit from VMAT. METHODS: Fifty-two patients that randomly selected from 205
      patients received VMAT at a single center were retrospectively replanned with s
      IMRT. For a fair comparison, the planning target volume (PTV) coverage of the 2
      plans was normalized to the same level. A standard planning constraint set was
      used; the constraints for the organs at risk (OARs) were individually adapted.
      The calculated doses to the PTV and OARs were compared for s-IMRT and VMAT plans
      generated using the Monaco treatment planning system. RESULTS: VMAT and s-IMRT
      plans had similar PTV coverage and OAR sparing within all T categories. However,
      in stratified analysis, VMAT plans lead to better or similar sparing of the OARs
      in early T category patients; and lead to poorer sparing of the OARs in advanced
      T category patients (P<0.05). VMAT shows significant advantages for low dose
      burden (P<0.05) compared with s-IMRT. The delivery time per fraction for VMAT
      (424+/-64 s) was shorter than s-IMRT (778 +/- 126 s, p<0.01). CONCLUSIONS: VMAT
      provides similar dose coverage of the PTVs and similar/better normal tissue
      sparing in early T category NPC, and poorer OARs sparing in advanced T category
      NPC. And VMAT shows significant advantages for low dose burden and delivery time.

PMID- 24086502
TI  - High-throughput profiling of anti-glycan humoral responses to SIV vaccination and
      challenge.
AB  - Recent progress toward an HIV vaccine highlights both the potential of vaccines
      to end the AIDS pandemic and the need to boost efficacy by incorporating
      additional vaccine strategies. Although many aspects of the immune response can
      contribute to vaccine efficacy, the key factors have not been defined fully yet.
      A particular area that may yield new insights is anti-glycan immune responses,
      such as those against the glycan shield that HIV uses to evade the immune system.
      In this study, we used glycan microarray technology to evaluate anti-glycan
      antibody responses induced by SIV vaccination and infection in a non-human
      primate model of HIV infection. This comprehensive profiling of circulating anti
      glycan antibodies found changes in anti-glycan antibody levels after both
      vaccination with the Ad5hr-SIV vaccine and SIV infection. Notably, SIV infection
      produced generalized declines in anti-glycan IgM antibodies in a number of
      animals. Additionally, some infected animals generated antibodies to the Tn
      antigen, which is a cryptic tumor-associated antigen exposed by premature
      termination of O-linked glycans; however, the Ad5hr-SIV vaccine did not induce
      anti-Tn IgG antibodies. Overall, this study demonstrates the potential
      contributions that glycan microarrays can make for HIV vaccine development. 

PMID- 24086504
TI  - Enzymatic synthesis of RNAs capped with nucleotide analogues reveals the
      molecular basis for substrate selectivity of RNA capping enzyme: impacts on RNA
      metabolism.
AB  - RNA cap binding proteins have evolved to specifically bind to the N7-methyl
      guanosine cap structure found at the 5' ends of eukaryotic mRNAs. The specificity
      of RNA capping enzymes towards GTP for the synthesis of this structure is
      therefore crucial for mRNA metabolism. The fact that ribavirin triphosphate was
      described as a substrate of a viral RNA capping enzyme, raised the possibility
      that RNAs capped with nucleotide analogues could be generated in cellulo. Owing
      to the fact that this prospect potentially has wide pharmacological implications,
      we decided to investigate whether the active site of the model Paramecium
      bursaria Chlorella virus-1 RNA capping enzyme was flexible enough to accommodate
      various purine analogues. Using this approach, we identified several key
      structural determinants at each step of the RNA capping reaction and generated
      RNAs harboring various different cap analogues. Moreover, we monitored the
      binding affinity of these novel capped RNAs to the eIF4E protein and evaluated
      their translational properties in cellulo. Overall, this study establishes a
      molecular rationale for the specific selection of GTP over other NTPs by RNA
      capping enzyme It also demonstrates that RNAs can be enzymatically capped with
      certain purine nucleotide analogs, and it also describes the impacts of modified
      RNA caps on specific steps involved in mRNA metabolism. For instance, our results
      indicate that the N7-methyl group of the classical N7-methyl guanosine cap is not
      always indispensable for binding to eIF4E and subsequently for translation when
      compensatory modifications are present on the capped residue. Overall, these
      findings have important implications for our understanding of the molecular
      determinants involved in both RNA capping and RNA metabolism.

PMID- 24086505
TI  - Seasonal variations in maternal provisioning of Crepidula fornicata (Gastropoda):
      fatty acid composition of females, embryos and larvae.
AB  - Recruitment success of marine invertebrate populations not only depends on the
      number of recruits but also on their quality which affects their survival. In
      species characterized by a mixed development (encapsulated embryonic development
      and release of planktotrophic larvae), the offspring quality depends on both
      maternal provisioning and larval feeding. Here, we investigated potential changes
      of maternal provisioning over the whole reproductive period in a gastropod with a
      mixed development: Crepidula fornicata. In its introduction area, C. fornicata
      reproduces from February to October, which implies that both adults and larvae
      are exposed to different food availabilities. Maternal provisioning was assessed
      by measuring the fatty acid (FA) composition of females, encapsulated embryos and
      larvae, in February, May, July and September 2009. FA are essential resources for
      the development of embryos and larvae, and are key biomarkers of offspring
      quality. Our results showed differences in FA composition between muscles,
      visceral masses, and encapsulated embryos. In particular, FA composition of
      embryos was similar to that of the visceral mass. Seasonal variations in FA
      composition were observed: in the middle of the reproductive season (May and
      July), female tissues and embryos showed a higher proportion of polyunsaturated
      fatty acids and especially omega3, as compared to the beginning and end of the
      reproductive season (February and September). This showed that through maternal
      provisioning the quality of C. fornicata offspring was higher in the middle of
      the reproductive season. Whether this would result in an increase of recruitment
      success and juvenile performance would require further investigations.

PMID- 24086506
TI  - Quantifying condition-dependent intracellular protein levels enables high
      precision fitness estimates.
AB  - Countless studies monitor the growth rate of microbial populations as a measure
      of fitness. However, an enormous gap separates growth-rate differences measurable
      in the laboratory from those that natural selection can distinguish efficiently.
      Taking advantage of the recent discovery that transcript and protein levels in
      budding yeast closely track growth rate, we explore the possibility that growth
      rate can be more sensitively inferred by monitoring the proteomic response to
      growth, rather than growth itself. We find a set of proteins whose levels, in
      aggregate, enable prediction of growth rate to a higher precision than direct
      measurements. However, we find little overlap between these proteins and those
      that closely track growth rate in other studies. These results suggest that, in
      yeast, the pathways that set the pace of cell division can differ depending on
      the growth-altering stimulus. Still, with proper validation, protein measurements
      can provide high-precision growth estimates that allow extension of phenotypic
      growth-based assays closer to the limits of evolutionary selection. 

PMID- 24086507
TI  - Dynamics of the major histocompatibility complex class I processing and
      presentation pathway in the course of malaria parasite development in human
      hepatocytes: implications for vaccine development.
AB  - Control of parasite replication exerted by MHC class I restricted CD8+ T-cells in
      the liver is critical for vaccination-induced protection against malaria. While
      many intracellular pathogens subvert the MHC class I presentation machinery, its
      functionality in the course of malaria replication in hepatocytes has not been
      characterized. Using experimental systems based on specific identification,
      isolation and analysis of human hepatocytes infected with P. berghei ANKA GFP or
      P. falciparum 3D7 GFP sporozoites we demonstrated that molecular components of
      the MHC class I pathway exhibit largely unaltered expression in malaria-infected
      hepatocytes until very late stages of parasite development. Furthermore, infected
      cells showed no obvious defects in their capacity to upregulate expression of
      different molecular components of the MHC class I machinery in response to pro
      inflammatory lymphokines or trigger direct activation of allo-specific or peptide
      specific human CD8+ T-cells. We further demonstrate that ectopic expression of
      circumsporozoite protein does not alter expression of critical genes of the MHC
      class I pathway and its response to pro-inflammatory cytokines. In addition, we
      identified supra-cellular structures, which arose at late stages of parasite
      replication, possessed the characteristic morphology of merosomes and exhibited
      nearly complete loss of surface MHC class I expression. These data have multiple
      implications for our understanding of natural T-cell immunity against malaria and
      may promote development of novel, efficient anti-malaria vaccines overcoming
      immune escape of the parasite in the liver. 

PMID- 24086508
TI  - Alocasia cucullata exhibits strong antitumor effect in vivo by activating
      antitumor immunity.
AB  - Chinese herbal medicines have long been used to treat various illnesses by
      modulating the human immune response. In this study, we investigate the immuno
      modulating effect and antitumor activity of Alocasia Cucullata (AC), a Chinese
      herb traditionally used to treat infection and cancer. We found that the whole
      water extract of AC roots could significantly attenuate tumor growth in mouse
      tumor models. The median survival time of the AC-treated mice was 43 days, 16
      days longer than that of the control group. Moreover, the AC-treated mice showed
      substantially higher induction of key antitumor cytokines, such as IL-2, IFN
      gamma, and TNF-alpha, indicating that AC may exert antitumor effect by activating
      antitumor immunity. To further pinpoint the cellular and molecular mechanism of
      AC, we studied the dose response of a human monocytic cell line, THP-1, to the
      whole water extract of AC. Treatment of the AC extract significantly induced THP
      1 differentiation into macrophage-like cells and the differentiated THP-1 showed
      expression of specific macrophage surface markers, such as CD11b and CD14, as
      well as productions of antitumor cytokines, e.g. IFN-gamma and TNF-alpha. Our
      data thus point to AC as potentially a new, alternative immuno-modulating herbal
      remedy for anticancer treatment. 

PMID- 24086509
TI  - Specific visualization of nitric oxide in the vasculature with two-photon
      microscopy using a copper based fluorescent probe.
AB  - To study the role and (sub) cellular nitric oxide (NO) constitution in various
      disease processes, its direct and specific detection in living cells and tissues
      is a major requirement. Several methods are available to measure the oxidation
      products of NO, but the detection of NO itself has proved challenging. We
      visualized NO production using a NO-sensitive copper-based fluorescent probe (Cu
      2FL2E) and two-photon laser scanning microscopy (TPLSM). Cu 2FL2E demonstrated
      high sensitivity and specificity for NO synthesis, combined with low
      cytotoxicity. Furthermore, Cu 2FL2E showed superior sensitivity over the
      conventionally used Griess assay. NO specificity of Cu 2FL2E was confirmed in
      vitro in human coronary arterial endothelial cells and porcine aortic endothelial
      cells using various triggers for NO production. Using TPLSM on ex vivo mounted
      murine carotid artery and aorta, the applicability of the probe to image NO
      production in both endothelial cells and smooth muscle cells was shown. NO
      production and time course was detected for multiple stimuli such as flow,
      acetylcholine and hydrogen peroxide and its correlation with vasodilation was
      demonstrated. NO-specific fluorescence and vasodilation was abrogated in the
      presence of NO-synthesis blocker L-NAME. Finally, the influence of carotid
      precontraction and vasorelaxation validated the functional properties of vessels.
      Specific visualization of NO production in vessels with Cu 2FL2E-TPLSM provides a
      valid method for studying spatial-temporal synthesis of NO in vascular biology at
      an unprecedented level. This approach enables investigation of the pathways
      involved in the complex interplay between NO and vascular (dys) function. 

PMID- 24086510
TI  - Quantifying variation in the ability of yeasts to attract Drosophila
      melanogaster.
AB  - Yeasts that invade and colonise fruit significantly enhance the volatile chemical
      diversity of this ecosystem. These modified bouquets are thought to be more
      attractive to Drosophila flies than the fruit alone, but the variance of
      attraction in natural yeast populations is uncharacterised. Here we investigate
      how a range of yeast isolates affect the attraction of female D. melanogaster to
      fruit in a simple two choice assay comparing yeast to sterile fruit. Of the 43
      yeast isolates examined, 33 were attractive and seven repellent to the flies. The
      results of isolate-versus-isolate comparisons provided the same relative
      rankings. Attractiveness varied significantly by yeast, with the strongly
      fermenting Saccharomyces species generally being more attractive than the mostly
      respiring non-Saccharomyces species (P = 0.0035). Overall the habitat (fruit or
      other) from which the isolates were directly sampled did not explain attraction
      (P = 0.2352). However, yeasts isolated from fruit associated niches were more
      attractive than those from non-fruit associated niches (P = 0.0188) regardless of
      taxonomic positioning. These data suggest that while attractiveness is primarily
      correlated with phylogenetic status, the ability to attract Drosophila is a
      labile trait among yeasts that is potentially associated with those inhabiting
      fruit ecosystems. Preliminary analysis of the volatiles emitted by four yeast
      isolates in grape juice show the presence/absence of ethanol and acetic acid were
      not likely explanations for the observed variation in attraction. These data
      demonstrate variation among yeasts for their ability to attract Drosophila in a
      pattern that is consistent with the hypothesis that certain yeasts are
      manipulating fruit odours to mediate interactions with their Drosophila dispersal
      agent. 

PMID- 24086511
TI  - Influenza transmission in a cohort of households with children: 2010-2011.
AB  - BACKGROUND: Households play a major role in community spread of influenza and are
      potential targets for mitigation strategies. METHODS: We enrolled and followed
      328 households with children during the 2010-2011 influenza season; this season
      was characterized by circulation of influenza A (H3N2), A (H1N1)pdm09 and type B
      viruses. Specimens were collected from subjects with acute respiratory illnesses
      and tested for influenza in real-time reverse transcriptase polymerase chain
      reaction (RT-PCR) assays. Influenza cases were classified as community-acquired
      or household-acquired, and transmission parameters estimated. RESULTS: Influenza
      was introduced to 78 (24%) households and transmission to exposed household
      members was documented in 23 households. Transmission was more likely in younger
      households (mean age <22 years) and those not reporting home humidification, but
      was not associated with household vaccination coverage. The secondary infection
      risk (overall 9.7%) was highest among young children (<9 years) and varied
      substantially by influenza type/subtype with the highest risk for influenza A
      (H3N2). The serial interval (overall 3.2 days) also varied by influenza type and
      was longest for influenza B. Duration of symptomatic illness was shorter in
      children compared with adults, and did not differ by influenza vaccination
      status. DISCUSSION: Prospective study of households with children over a single
      influenza season identified differences in household transmission by influenza
      type/subtype, subject age, and home humidification, suggesting possible targets
      for interventions to reduce transmission.

PMID- 24086512
TI  - Proteomics analysis of human obesity reveals the epigenetic factor HDAC4 as a
      potential target for obesity.
AB  - Sedentary lifestyle and excessive energy intake are prominent contributors to
      obesity; a major risk factors for the development of insulin resistance, type 2
      diabetes and cardiovascular diseases. Elucidating the molecular mechanisms
      underlying these chronic conditions is of relevant importance as it might lead to
      the identification of novel anti-obesity targets. The purpose of the current
      study is to investigate differentially expressed proteins between lean and obese
      subjects through a shot-gun quantitative proteomics approach using peripheral
      blood mononuclear cells (PBMCs) extracts as well as potential modulation of those
      proteins by physical exercise. Using this approach, a total of 47 proteins showed
      at least 1.5 fold change between lean and obese subjects. In obese, the proteomic
      profiling before and after 3 months of physical exercise showed differential
      expression of 38 proteins. Thrombospondin 1 (TSP1) was among the proteins that
      were upregulated in obese subjects and then decreased by physical exercise.
      Conversely, the histone deacetylase 4 (HDAC4) was downregulated in obese subjects
      and then induced by physical exercise. The proteomic data was further validated
      by qRT-PCR, Western blot and immunohistochemistry in both PBMCs and adipose
      tissue. We also showed that HDAC4 levels correlated positively with maximum
      oxygen consumption (VO2 Max) but negatively with body mass index, percent body
      fat, and the inflammatory chemokine RANTES. In functional assays, our data
      indicated that ectopic expression of HDAC4 significantly impaired TNF-alpha
      dependent activation of NF-kappaB, establishing thus a link between HDAC4 and
      regulation of the immune system. Together, the expression pattern of HDAC4 in
      obese subjects before and after physical exercise, its correlation with various
      physical, clinical and metabolic parameters along with its inhibitory effect on
      NF-kappaB are suggestive of a protective role of HDAC4 against obesity. HDAC4
      could therefore represent a potential therapeutic target for the control and
      management of obesity and presumably insulin resistance. 

PMID- 24086514
TI  - Association of polymorphisms in pharmacogenetic candidate genes (OPRD1, GAL,
      ABCB1, OPRM1) with opioid dependence in European population: a case-control
      study.
AB  - It is becoming increasingly evident that genetic variants contribute to the
      development of opioid addiction. An elucidation of these genetic factors is
      crucial for a better understanding of this chronic disease and may help to
      develop novel therapeutic strategies. In recent years, several candidate genes
      were implicated in opioid dependence. However, most study findings have not been
      replicated and additional studies are required before reported associations can
      be considered robust. Thus, the major objective of this study was to replicate
      earlier findings and to identify new genetic polymorphisms contributing to the
      individual susceptibility to opioid addiction, respectively. Therefore, a
      candidate gene association study was conducted including 142 well-phenotyped long
      term opioid addicts undergoing opioid maintenance therapy and 142 well-matched
      healthy controls. In both study groups, 24 single nucleotide polymorphisms
      predominantly located in pharmacogenetic candidate genes have been genotyped
      using an accurate mass spectrometry based method. The most significant
      associations with opioid addiction (remaining significant after adjustment for
      multiple testing) were observed for the rs948854 SNP in the galanin gene (GAL, p
      = 0.001) and the rs2236861 SNP in the delta opioid receptor gene (OPRD1, p =
      0.001). Moreover, an association of the ATP binding cassette transporter 1
      (ABCB1) variant rs1045642 and the Mu Opioid receptor (OPRM1) variant rs9479757
      with opioid addiction was observed. The present study provides further support
      for a contribution of GAL and OPRD1 variants to the development of opioid
      addiction. Furthermore, our results indicate a potential contribution of OPRM1
      and ABCB1 SNPs to the development of this chronic relapsing disease. Therefore it
      seems important that these genes are addressed in further addiction related
      studies. 

PMID- 24086513
TI  - Characterisation and expression of calpain family members in relation to
      nutritional status, diet composition and flesh texture in gilthead sea bream
      (Sparus aurata).
AB  - Calpains are non-lysosomal calcium-activated neutral proteases involved in a wide
      range of cellular processes including muscle proteolysis linked to post-mortem
      flesh softening. The aims of this study were (a) to characterise several members
      of the calpain system in gilthead sea bream and (b) to examine their expression
      in relation to nutritional status and muscle tenderisation. We identified the
      complete open reading frame of gilthead sea bream calpains1-3, sacapn1, sacapn2,
      sacapn3, and two paralogs of the calpain small subunit1, sacapns1a and sacapns1b.
      Proteins showed 63-90% sequence identity compared with sequences from mammals and
      other teleost fishes, and the characteristic domain structure of vertebrate
      calpains. Transcripts of sacapn1, sacapn2, sacapns1a and sacapns1b had a wide
      tissue distribution, whereas sacapn3 was almost exclusively detected in skeletal
      muscle. Next, we assessed transcript expression in skeletal muscle following
      alteration of nutritional status by (a) fasting and re-feeding or (b) feeding
      four experimental diets with different carbohydrate-to-protein ratios. Fasting
      significantly reduced plasma glucose and increased free fatty acids and
      triglycerides, together with a significant increase in sacapns1b expression.
      Following 7 days of re-feeding, plasma parameters returned to fed values and
      sacapn1, sacapn2, sacapns1a and sacapns1b expression was significantly reduced.
      Furthermore, an increase in dietary carbohydrate content (11 to 39%) diminished
      growth but increased muscle texture, which showed a significant correlation with
      decreased sacapn1 and sacapns1a expression, whilst the other calpains remained
      unaffected. This study has demonstrated that calpain expression is modulated by
      nutritional status and diet composition in gilthead sea bream, and that the
      expression of several calpain members is correlated with muscle texture,
      indicating their potential use as molecular markers for flesh quality in
      aquaculture production. 

PMID- 24086515
TI  - Serum soluble CD14 is a potential prognostic indicator of recurrence of human
      breast invasive ductal carcinoma with Her2-enriched subtype.
AB  - In clinical practice, breast cancers with lymph node positive, ER/PR-negative and
      overexpressed human epidermal growth factor receptor 2 (LN+ER/PR-Her2+) have high
      risk of recurrence, but the effective biomarkers of prognostic for this type
      tumor are still lacking. Since breast cancers with LN+ER/PR-Her2+ is at higher
      risk of recurrence than those with LN-ER/PR+Her2-. The differential proteins
      between those two groups could be related to the risk of recurrence. Herein, we
      report that serum soluble CD14 (sCD14) was revealed as the stable differential
      protein between LN+ER/PR-Her2+ (n=50) and LN-ER/PR+Her2- (n=50) breast cancer
      patients by proteomics analysis. To validate sCD14 as a biomarker for predicting
      recurrence of breast cancer, 90 breast cancer patients with LN+ER/PR-Her2+ and 93
      patients with LN-ER/PR+Her2- were recruited. The patients with higher level of
      serum sCD14 at primary surgery showed to be at significantly lower risk of
      relapse in 3 years follow-up than those with lower level of serum sCD14 at
      primary surgery. The levels of serum sCD14 at primary surgery were significantly
      correlated to the risk of 3-year recurrence of LN+ER/PR-Her2+ breast cancer and
      the corresponding AUC of the ROC curve was 0.833 (95% CI, and 0.742 to 0.920).
      Therefore, we surmise that serum sCD14 could be a potential biomarker for
      predicting the prognosis of breast invasive ductal carcinoma with LN+ER/PR-Her2+.

PMID- 24086516
TI  - MGMT Leu84Phe polymorphism contributes to cancer susceptibility: evidence from 44
      case-control studies.
AB  - BACKGROUND: O(6)-methylguanine-DNA methyltransferase is one of the few proteins
      to directly remove alkylating agents in the human DNA direct reversal repair
      pathway. A large number of case-control studies have been conducted to explore
      the association between MGMT Leu84Phe polymorphism and cancer risk. However, the
      results were not consistent. METHODS: We carried out a meta-analysis of 44 case
      control studies to clarify the association between the Leu84Phe polymorphism and
      cancer risk. RESULTS: Overall, significant association of the T allele with
      cancer susceptibility was verified with meta-analysis under a recessive genetic
      model (P<0.001, OR=1.30, 95%CI 1.24-1.50) and TT versus CC comparison (P=0.001,
      OR=1.29, 95% CI 1.12-1.50). In subgroup analysis, a significant increased risk
      was found for lung cancer (TT versus CC, P=0.027, OR=1.67, 95% CI 1.06-2.63;
      recessive genetic model, P=0.32, OR=1.64, 95% CI 1.04-2.58), whereas risk of
      colorectal cancer was significantly low under a dominant genetic model (P=0.019,
      OR=0.84, 95% CI 0.72-0.97). Additionally, a significant association between TT
      genetic model and total cancer risk was found in the Caucasian population (TT
      versus CC, P=0.014, OR=1.29, 95% CI 1.05-1.59; recessive genetic model, P=0.009,
      OR=1.31, 95% CI 1.07-1.61), but not in the Asian population. An increased risk
      for lung cancer was also verified in the Caucasian population (TT versus CC,
      P=0.035, OR=1.62, 95% CI 1.04-2.53; recessive genetic model, P=0.048, OR=1.57,
      95% CI 1.01-2.45). CONCLUSIONS: These results suggest that MGMT Leu84Phe
      polymorphism might contribute to the susceptibility of certain cancers.

PMID- 24086517
TI  - Steady-state metabolite concentrations reflect a balance between maximizing
      enzyme efficiency and minimizing total metabolite load.
AB  - Steady-state metabolite concentrations in a microorganism typically span several
      orders of magnitude. The underlying principles governing these concentrations
      remain poorly understood. Here, we hypothesize that observed variation can be
      explained in terms of a compromise between factors that favor minimizing
      metabolite pool sizes (e.g. limited solvent capacity) and the need to effectively
      utilize existing enzymes. The latter requires adequate thermodynamic driving
      force in metabolic reactions so that forward flux substantially exceeds reverse
      flux. To test this hypothesis, we developed a method, metabolic tug-of-war
      (mTOW), which computes steady-state metabolite concentrations in microorganisms
      on a genome-scale. mTOW is shown to explain up to 55% of the observed variation
      in measured metabolite concentrations in E. coli and C. acetobutylicum across
      various growth media. Our approach, based strictly on first thermodynamic
      principles, is the first method that successfully predicts high-throughput
      metabolite concentration data in bacteria across conditions. 

PMID- 24086518
TI  - The non-protein amino acid BMAA is misincorporated into human proteins in place
      of L-serine causing protein misfolding and aggregation.
AB  - Mechanisms of protein misfolding are of increasing interest in the aetiology of
      neurodegenerative diseases characterized by protein aggregation and tangles
      including Amyotrophic Lateral Sclerosis (ALS), Alzheimer's disease (AD),
      Parkinson's disease (PD), Lewy Body Dementia (LBD), and Progressive Supranuclear
      Palsy (PSP). Some forms of neurodegenerative illness are associated with
      mutations in genes which control assembly of disease related proteins. For
      example, the mouse sticky mutation sti, which results in undetected mischarging
      of tRNA(Ala) with serine resulting in the substitution of serine for alanine in
      proteins causes cerebellar Purkinje cell loss and ataxia in laboratory animals.
      Replacement of serine 422 with glutamic acid in tau increases the propensity of
      tau aggregation associated with neurodegeneration. However, the possibility that
      environmental factors can trigger abnormal folding in proteins remains relatively
      unexplored. We here report that a non-protein amino acid, beta-N-methylamino-L
      alanine (BMAA), can be misincorporated in place of L-serine into human proteins.
      We also report that this misincorporation can be inhibited by L-serine.
      Misincorporation of BMAA into human neuroproteins may shed light on putative
      associations between human exposure to BMAA produced by cyanobacteria and an
      increased incidence of ALS.

PMID- 24086519
TI  - Toll-like receptor 4 deficiency accelerates the development of insulin-deficient
      diabetes in non-obese diabetic mice.
AB  - BACKGROUND/OBJECTIVE: Toll-like receptors (TLR) mediate the recognition of
      microbial constituents and stress-induced endogenous ligands by the immune
      system. They may also be involved in the maintenance or break down of tolerance
      against autologous antigens. The aim of our investigation was to study the
      consequence of TLR4 deficiency on the development of insulin-deficient diabetes
      in the NOD mouse. METHODS: The TLR4 defect of the C57BL/10ScN mouse was
      backcrossed onto the NOD background and the effect of TLR4 deficiency on diabetes
      development was analysed by in vivo and in vitro studies. RESULTS: Compared to
      animals with wildtype TLR4 expression (TLR4(+/+)), female NOD mice carrying a
      homozygous TLR4 defect (TLR4(-/-)), showed significant acceleration of diabetes
      development, with a younger age at diabetes onset (TLR4 (+/+) 177+/-22 d, TLR(-/
      ): 118+/-21 d; p<0.01). Pancreata of 120 d old TLR4(-/-) NOD mice revealed
      increased proportions of islets with advanced stages of immune cell infiltration
      compared to TLR4(+/+) mice (p<0.05). TLR4 deficiency did not affect the
      susceptibility of islet cells to the beta cell damaging mediators nitric oxide or
      the inflammatory cytokines tumor necrosis factor alpha, interleukin-1 beta and
      interferon gamma. The lack of TLR4 further had no effect on the frequency of
      regulatory T-cells but reduced their capacity to inhibit T-cell proliferation.
      CONCLUSIONS: Our findings demonstrate that TLR4 deficiency results in an
      acceleration of diabetes development and immune cell infiltration of islets in
      NOD mice. We conclude that TLR4 is involved in the progression of the insulitis
      process thereby controlling the development of insulin-deficient diabetes in NOD
      mice.

PMID- 24086520
TI  - The importance of genetic and shared environmental factors for the associations
      between job demands, control, support and burnout.
AB  - Within occupational health research, one of the most influential models is the
      Job Demands-Control-Support model. Numerous studies have applied the model to
      different domains, with both physical and psychological health outcomes, such as
      burnout. The twin design provides a unique and powerful research methodology for
      examining the effects of environmental risk factors on burnout while taking
      familial factors (genetic and shared environment) into account. The aim of the
      present study was to investigate the impact of familial factors on the
      associations of burnout with job demands, control and support. A total of 14,516
      individuals from the Swedish Twin Registry, who were born between 1959 and 1986,
      and who participated in the Study of Twin Adults: Genes and Environment (STAGE)
      by responding to a web-based questionnaire in 2005, were included in the
      analyses. Of these, there were 5108 individuals in complete same-sex twin pairs.
      Co-twin control analyses were performed using linear mixed modeling, comparing
      between-pairs effects and within-pair effects, stratified also by zygosity and
      sex. The results indicate that familial factors are of importance in the
      association between support and burnout in both women and men, but not between
      job demands and burnout. There are also tendencies towards familial factors being
      involved in the association between control and burnout in men. These results
      offer increased understanding of the mechanisms involved in the associations
      between work stress and burnout.

PMID- 24086521
TI  - The transcriptional regulator Np20 is the zinc uptake regulator in Pseudomonas
      aeruginosa.
AB  - Zinc is essential for all bacteria, but excess amounts of the metal can have
      toxic effects. To address this, bacteria have developed tightly regulated zinc
      uptake systems, such as the ZnuABC zinc transporter which is regulated by the Fur
      like zinc uptake regulator (Zur). In Pseudomonas aeruginosa, a Zur protein has
      yet to be identified experimentally, however, sequence alignment revealed that
      the zinc-responsive transcriptional regulator Np20, encoded by np20 (PA5499),
      shares high sequence identity with Zur found in other bacteria. In this study, we
      set out to determine whether Np20 was functioning as Zur in P. aeruginosa. Using
      RT-PCR, we determined that np20 (hereafter known as zur) formed a polycistronic
      operon with znuC and znuB. Mutant strains, lacking the putative znuA, znuB, or
      znuC genes were found to grow poorly in zinc deplete conditions as compared to
      wild-type strain PAO1. Intracellular zinc concentrations in strain PAO-Zur
      (Deltazur) were found to be higher than those for strain PAO1, further
      implicating the zur as the zinc uptake regulator. Reporter gene fusions and real
      time RT-PCR revealed that transcription of znuA was repressed in a zinc-dependent
      manner in strain PAO1, however zinc-dependent transcriptional repression was
      alleviated in strain PAO-Zur, suggesting that the P. aeruginosa Zur homolog
      (ZurPA) directly regulates expression of znuA. Electrophoretic mobility shift
      assays also revealed that recombinant ZurPA specifically binds to the promoter
      region of znuA and does not bind in the presence of the zinc chelator N,N',N
      tetrakis(2-pyridylmethyl) ethylenediamine (TPEN). Taken together, these data
      support the notion that Np20 is the P. aeruginosa Zur, which regulates the
      transcription of the genes encoding the high affinity ZnuABC zinc transport
      system. 

PMID- 24086522
TI  - Comparative analysis of ESBL-positive Escherichia coli isolates from animals and
      humans from the UK, The Netherlands and Germany.
AB  - The putative virulence and antimicrobial resistance gene contents of extended
      spectrum beta-lactamase (ESBL)-positive E. coli (n=629) isolated between 2005 and
      2009 from humans, animals and animal food products in Germany, The Netherlands
      and the UK were compared using a microarray approach to test the suitability of
      this approach with regard to determining their similarities. A selection of
      isolates (n=313) were also analysed by multilocus sequence typing (MLST).
      Isolates harbouring bla(CTX-M-group-1) dominated (66%, n=418) and originated from
      both animals and cases of human infections in all three countries; 23% (n=144) of
      all isolates contained both bla(CTX-M-group-1) and bla(OXA-1-like) genes,
      predominantly from humans (n=127) and UK cattle (n=15). The antimicrobial
      resistance and virulence gene profiles of this collection of isolates were highly
      diverse. A substantial number of human isolates (32%, n=87) did not share more
      than 40% similarity (based on the Jaccard coefficient) with animal isolates. A
      further 43% of human isolates from the three countries (n=117) were at least 40%
      similar to each other and to five isolates from UK cattle and one each from Dutch
      chicken meat and a German dog; the members of this group usually harboured genes
      such as mph(A), mrx, aac(6')-Ib, catB3, bla(OXA-1-like) and bla(CTX-M-group-1).
      forty-four per cent of the MLST-typed isolates in this group belonged to ST131
      (n=18) and 22% to ST405 (n=9), all from humans. Among animal isolates subjected
      to MLST (n=258), only 1.2% (n=3) were more than 70% similar to human isolates in
      gene profiles and shared the same MLST clonal complex with the corresponding
      human isolates. The results suggest that minimising human-to-human transmission
      is essential to control the spread of ESBL-positive E. coli in humans.

PMID- 24086524
TI  - Occupational styrene exposure induces stress-responsive genes involved in
      cytoprotective and cytotoxic activities.
AB  - OBJECTIVE: The aim of this study was to evaluate the expression of a panel of
      genes involved in toxicology in response to styrene exposure at levels below the
      occupational standard setting. METHODS: Workers in a fiber glass boat industry
      were evaluated for a panel of stress- and toxicity-related genes and associated
      with biochemical parameters related to hepatic injury. Urinary styrene
      metabolites (MA+PGA) of subjects and environmental sampling data collected for
      air at workplace were used to estimate styrene exposure. RESULTS: Expression
      array analysis revealed massive upregulation of genes encoding stress-responsive
      proteins (HSPA1L, EGR1, IL-6, IL-1beta, TNSF10 and TNFalpha) in the styrene
      exposed group; the levels of cytokines released were further confirmed in serum.
      The exposed workers were then stratified by styrene exposure levels. EGR1 gene
      upregulation paralleled the expression and transcriptional protein levels of IL
      6, TNSF10 and TNFalpha in styrene exposed workers, even at low level. The
      activation of the EGR1 pathway observed at low-styrene exposure was associated
      with a slight increase of hepatic markers found in highly exposed subjects, even
      though they were within normal range. The ALT and AST levels were not affected by
      alcohol consumption, and positively correlated with urinary styrene metabolites
      as evaluated by multiple regression analysis. CONCLUSION: The pro-inflammatory
      cytokines IL-6 and TNFalpha are the primary mediators of processes involved in
      the hepatic injury response and regeneration. Here, we show that styrene induced
      stress responsive genes involved in cytoprotection and cytotoxicity at low
      exposure, that proceed to a mild subclinical hepatic toxicity at high-styrene
      exposure.

PMID- 24086525
TI  - Comparative susceptibility of different biological forms of Anopheles stephensi
      to Plasmodium berghei ANKA strain.
AB  - BACKGROUND: There are varying degrees of compatibility between malaria parasite
      mosquito species, and understanding this compatibility may be crucial for
      developing effective transmission-blocking vaccines. This study investigates the
      compatibility of different biological forms of a malaria vector, Anopheles
      stephensi, to Plasmodium berghei ANKA strain. METHODS: Several biologically
      different and allopatric forms of A. stephensi were studied. Three forms were
      isolated from different regions of southern Iran: the variety mysorensis, the
      intermediate form and the native type form, and an additional type form
      originated from India (Beech strain).The mosquitoes were experimentally infected
      with P. berghei to compare their susceptibility to parasitism. Anti-mosquito
      midgut antiserum was then raised in BALB/cs mice immunized against gut antigens
      from the most susceptible form of A. stephensi (Beech strain), and the efficacy
      of the antiserum was assessed in transmission-blocking assays conducted on the
      least susceptible mosquito biological form. RESULTS: The susceptibility of
      different biological forms of A. stephensi mosquito to P. berghei was
      specifically inter-type varied. The Beech strain and the intermediate form were
      both highly susceptible to infection, with higher oocyst and sporozoite infection
      rates than intermediate and mysorensis forms. The oocyst infection, and
      particularly sporozite infection, was lowest in the mysorensis strain. Antiserum
      raised against midgut proteins of the Indian Beech type form blocked infection in
      this mosquito population, but it was ineffective at blocking both oocyst and
      sporozoite development in the permissive but geographically distant intermediate
      form mosquitoes. This suggests that a strong degree of incompatibility exists
      between the mosquito strains in terms of midgut protein(s) acting as putative
      ookinete receptors. CONCLUSIONS: The incompatibility in the midgut protein
      profiles between two biological forms of A. stephensi demonstrates a well
      differentiated population structure according to geographical origin. Therefore,
      the design of potential transmission-blocking strategies should incorporate a
      more thorough understanding of intra-species variations in host-parasite
      interactions.

PMID- 24086523
TI  - Effects of specific multi-nutrient enriched diets on cerebral metabolism,
      cognition and neuropathology in AbetaPPswe-PS1dE9 mice.
AB  - Recent studies have focused on the use of multi-nutrient dietary interventions in
      search of alternatives for the treatment and prevention of Alzheimer's disease
      (AD). In this study we investigated to which extent long-term consumption of two
      specific multi-nutrient diets can modulate AD-related etiopathogenic mechanisms
      and behavior in 11-12-month-old AbetaPPswe-PS1dE9 mice. Starting from 2 months of
      age, male AbetaPP-PS1 mice and wild-type littermates were fed either a control
      diet, the DHA+EPA+UMP (DEU) diet enriched with uridine monophosphate (UMP) and
      the omega-3 fatty acids docosahexaenoic acid (DHA) and eicosapentaenoic acid
      (EPA), or the Fortasyn(r) Connect (FC) diet enriched with the DEU diet plus
      phospholipids, choline, folic acid, vitamins and antioxidants. We performed
      behavioral testing, proton magnetic resonance spectroscopy, immunohistochemistry,
      biochemical analyses and quantitative real-time PCR to gain a better
      understanding of the potential mechanisms by which these multi-nutrient diets
      exert protective properties against AD. Our results show that both diets were
      equally effective in changing brain fatty acid and cholesterol profiles. However,
      the diets differentially affected AD-related pathologies and behavioral measures,
      suggesting that the effectiveness of specific nutrients may depend on the dietary
      context in which they are provided. The FC diet was more effective than the DEU
      diet in counteracting neurodegenerative aspects of AD and enhancing processes
      involved in neuronal maintenance and repair. Both diets elevated interleukin
      1beta mRNA levels in AbetaPP-PS1 and wild-type mice. The FC diet additionally
      restored neurogenesis in AbetaPP-PS1 mice, decreased hippocampal levels of
      unbound choline-containing compounds in wild-type and AbetaPP-PS1 animals,
      suggesting diminished membrane turnover, and decreased anxiety-related behavior
      in the open field behavior. In conclusion, the current data indicate that
      specific multi-nutrient diets can influence AD-related etiopathogenic processes.
      Intervention with the FC diet might be of interest for several other
      neurodegenerative and neurological disorders. 

PMID- 24086526
TI  - Sorafenib sensitizes solid tumors to Apo2L/TRAIL and Apo2L/TRAIL receptor agonist
      antibodies by the Jak2-Stat3-Mcl1 axis.
AB  - BACKGROUND: Approximately half of tumor cell lines are resistant to the tumor
      selective apoptotic effects of tumor necrosis factor-related apoptosis-inducing
      ligand (Apo22L/TRAIL). Previously, we showed that combining Apo2L/TRAIL with
      sorafenib, a multikinase inhibitor, results in dramatic efficacy in Apo2L/TRAIL
      resistant tumor xenografts via inhibition of Mcl-1. Soluble Apo2L/TRAIL is
      capable of binding to several surface receptors, including the pro-apoptotic
      death receptors, DR4 and DR5, and decoy receptors, DcR1 and DcR2. Monoclonal
      antibodies targeting either of these death receptors are being investigated as
      antitumor agents in clinical trials. We hypothesized that sorafenib and
      Apo2L/TRAIL or Apo2L/TRAIL death receptor agonist (TRA) antibodies against DR4
      (mapatumumab) and DR5 (lexatumumab) will overcome resistance to Apo2L/TRAIL
      mediated apoptosis and as increase antitumor efficacy in Apo2L/TRAIL-sensitive
      solid tumors. METHODOLOGY/PRINCIPAL FINDINGS: We found that Apo2L/TRAIL or TRA
      antibodies combined with sorafenib synergistically reduce cell growth and
      increase cell death across a panel of solid tumor cell lines in vitro. This panel
      included human breast, prostate, colon, liver and thyroid cancers. The
      cooperativity of these combinations was also observed in vivo, as measured by
      tumor volume and TUNEL staining as a measure of apoptosis. We found that
      sorafenib inhibits Jak/Stat3 signaling and downregulates their target genes,
      including cyclin D1, cyclin D2 and Mcl-1, in a dose-dependent manner.
      CONCLUSIONS/SIGNIFICANCE: The combination of sorafenib with Apo2L/TRAIL or
      Apo2L/TRAIL receptor agonist antibodies sensitizes Apo2L/TRAIL-resistant cells
      and increases the sensitivity of Apo2L/TRAIL-sensitive cells. Our findings
      demonstrate the involvement of the Jak2-Stat3-Mcl1 axis in response to sorafenib
      treatment, which may play a key role in sorafenib-mediated sensitization to
      Apo2L/TRAIL.

PMID- 24086528
TI  - Bicycle helmet wearing is not associated with close motor vehicle passing: a re
      analysis of Walker, 2007.
AB  - OBJECTIVES: To re-analyse bicycle overtaking data collected by Walker (2007) with
      a view to assess factors associated with close passing (<1 m), to adjust for
      other observed factors in a multivariable analysis, and to assess the extent to
      which the sample size in the original analysis may have contributed to spurious
      results. METHOD: A re-analysis of 2,355 motor vehicle passing events recorded by
      Walker that includes information on cyclist's distance to the kerb, vehicle size
      and colour, city of observation, time of day, whether the event occurred while in
      a bikelane and helmet wearing. Each variable was considered for a final,
      multivariable model using purposeful selection of variables. The analysis was
      repeated using multiple logistic regression with passing distance dichotomised by
      the one metre rule. Bootstrap p-values were computed using sample sizes computed
      from conventional values of power and effect size. RESULTS: The previously
      observed significant association between passing distance and helmet wearing was
      not found when dichotomised by the one metre rule. Other factors were found to be
      significantly associated with close passing including cyclists' distance to the
      kerb, vehicle size and city of observation (Salisbury or Bristol, UK). P-values
      from bootstrap samples indicate the significance of helmet wearing resulted from
      an overly large sample size. CONCLUSIONS: After re-analysis of Walker's data,
      helmet wearing is not associated with close motor vehicle passing. The results,
      however, highlight other more important factors that may inform effective bicycle
      safety strategies.

PMID- 24086527
TI  - Overexpression of meloe gene in melanomas is controlled both by specific
      transcription factors and hypomethylation.
AB  - The melanoma antigens MELOE-1 and MELOE-2 are encoded by a messenger, called
      meloe, overexpressed in melanomas compared with other tumour cell types and
      healthy tissues. They are both able to elicit melanoma-specific T cell responses
      in melanoma patients, and MELOE-1-specific CD8 T cells have been involved in
      melanoma immunosurveillance. With the aim to develop immunotherapies targeting
      this antigen, we investigated the transcriptional mechanisms leading to the
      preferential expression of meloe messenger in the melanocytic lineage. We defined
      the minimal promoter region of meloe gene and identified binding motifs for a set
      of transcription factors. Using mutagenesis, co-transfection experiments and
      chromatin immunoprecipitation, we showed that transcription factors involved in
      meloe promoter activity in melanomas were the melanocytic specific SOX9 and SOX10
      proteins together with the activated P-CREB protein. Furthermore, we showed that
      meloe promoter was hypomethylated in melanomas and melanocytes, and
      hypermethylated in colon cancer cell lines and mesotheliomas, thus explaining the
      absence of P-CREB binding in these cell lines. This was a second key to explain
      the overerexpression of meloe messenger in the melanocytic lineage. To our
      knowledge, such a dual transcriptional control conferring tissue-specificity has
      never been described for the expression of tumour antigens. 

PMID- 24086529
TI  - First characterization of bacterial pathogen, Vibrio alginolyticus, for Porites
      andrewsi White syndrome in the South China Sea.
AB  - BACKGROUND: White syndrome, a term for scleractinian coral disease with
      progressive tissue loss, is known to cause depressed growth and increased
      morality of coral reefs in the major oceans around the world, and the occurrence
      of this disease has been frequently reported in the past few decades.
      Investigations during April to September in both 2010 and 2011 identified
      widespread Porites andrewsi White syndrome (PAWS) in Xisha Archipelago, South
      China Sea. However, the causes and etiology of PAWS have been unknown.
      METHODOLOGY/PRINCIPAL FINDINGS: A transmission experiment was performed on P.
      andrewsi in the Qilianyu Subgroup (QLY). The results showed that there was a
      significant (P <= 0.05) difference between test and control groups after 28 days
      if the invalid replicates were excluded. Rates of tissue loss ranged from 0.90
      10.76 cm(2) d(-1) with a mean of 5.40 +/- 3.34 cm(2) d(-1) (mean +/- SD).
      Bacterial strains were isolated from the PAWS corals at the disease outbreak
      sites in QLY of the Xisha Archipelago, South China Sea, and included in
      laboratory-based infection trials to satisfy Koch's postulates for establishing
      causality. Following exposure to bacterial concentrations of 10(5) cells mL(-1),
      the infected colonies exhibited similar signs to those observed in the field.
      Using phylogenetic 16S rRNA gene analysis, classical phenotypic trait comparison,
      Biolog automatic identification system, MALDI-TOF mass spectrometry and MALDI
      Biotyper method, two pathogenic strains were identified as Vibrio alginolyticus .
      CONCLUSION/SIGNIFICANCE: This is the first report of V. alginolyticus as a
      pathogenic agent of PAWS in the South China Sea. Our results point out an urgent
      need to develop sensitive detection methods for V. alginolyticus virulence
      strains and robust diagnostics for coral disease caused by this and Vibrio
      pathogenic bacterium in the South China Sea.

PMID- 24086530
TI  - Simulating society transitions: standstill, collapse and growth in an evolving
      network model.
AB  - We developed a model society composed of various occupations that interact with
      each other and the environment, with the capability of simulating three widely
      recognized societal transition patterns: standstill, collapse and growth, which
      are important compositions of society evolving dynamics. Each occupation is
      equipped with a number of inhabitants that may randomly flow to other
      occupations, during which process new occupations may be created and then
      interact with existing ones. Total population of society is associated with
      productivity, which is determined by the structure and volume of the society. We
      ran the model under scenarios such as parasitism, environment fluctuation and
      invasion, which correspond to different driving forces of societal transition,
      and obtained reasonable simulation results. This work adds to our understanding
      of societal evolving dynamics as well as provides theoretical clues to
      sustainable development.

PMID- 24086531
TI  - The neural mechanism of encountering misjudgment by the justice system.
AB  - Although misjudgment is an issue of primary concern to the justice system and
      public safety, the response to misjudgment by the human brain remains unclear. We
      used fMRI to record neural activity in participants that encountered four
      possible judgments by the justice system with two basic components: whether the
      judgment was right or wrong [accuracy: right vs. wrong (misjudgment)] and whether
      the judgment was positive or negative [valence: positive vs. negative]. As
      hypothesized, the rostral ACC specifically processes the accuracy of judgment,
      being more active for misjudgment than for right judgment, while the striatum was
      uniquely responsible for the valence of judgment, being recruited to a larger
      extent by positive judgment compared to negative judgment. Furthermore, the
      activity in the rACC for positive misjudgments was positively correlated with
      that for negative misjudgments, which confirmed the misjudgment-specificity of
      the rACC. These results demonstrate that the brain can distinguish a misjudgment
      from a right judgment and regard a misjudgment as an emotionally arousing
      stimulus, independent of whether it is positive or negative, while positive
      judgment is considered as hedonic information, regardless of whether it is right
      or wrong. Our study is the first to reveal the neural mechanism that underlies
      judgment processing. This mechanism may constitute the basis of future studies to
      develop a novel marker for the detection of lies. 

PMID- 24086533
TI  - Increased expression of Yes-associated protein 1 in hepatocellular carcinoma with
      stemness and combined hepatocellular-cholangiocarcinoma.
AB  - Combined hepatocellular-cholangiocarcinoma (cHC-CC) and some hepatocellular
      carcinomas (HCCs) express stemness-related markers, such as epithelial adhesion
      molecule (EpCAM) and keratin 19 (K19), the expression of which has been reported
      to be associated with more aggressive behavior therein than in HCCs without. Yes
      associated protein 1 (YAP1), a potential oncogene, is known to promote stem cell
      proliferation. In the present study, YAP1 expression and clinicopathological
      features were evaluated and compared among three groups comprising 36 HCCs that
      expressed both EpCAM and K19, 64 HCCs that did not express EpCAM and K19, and 58
      cHC-CCs, which consisted of 38 cases of the classical type and 20 cases of the
      intermediate-cell subtype. YAP1 expression was more frequently noted in
      EpCAM(+)/K19(+) HCCs (55.6%) and in cHC-CCs (67.2%) than in EpCAM(-)/K19(-) HCCs
      (17.2%) (P<0.001 for both). In cHC-CCs, YAP1 expression was observed in 63% of
      classical type cHC-CCs and in 75% of the intermediate subtype; moreover, such
      expression was correlated with poorer histological differentiation (P = 0.017)
      and was more frequently noted in transition zones than in HCC areas (P = 0.060).
      Disease-free and overall survival showed a statistically significant difference
      among the three groups: disease-free survival was highest for EpCAM(-)/K19(-)
      HCCs and lowest for cHC-CCs, with EpCAM(+)/K19(+) HCCs falling in between
      (P<0.05). Overall survival rate was lower in HCCs and cHC-CCs with YAP1
      expression compared to those without (P = 0.05), whereas disease-free survival
      showed no significant difference according to YAP1 expression. Increased YAP1
      expression was more frequently found in cHC-CCs and HCCs with stemness than in
      HCCs without, and a YAP1 pathway is suggested to be involved in the obtainment
      stemness characteristics in HCCs and cHC-CCs. 

PMID- 24086532
TI  - Chl1 DNA helicase regulates Scc2 deposition specifically during DNA-replication
      in Saccharomyces cerevisiae.
AB  - The conserved family of cohesin proteins that mediate sister chromatid cohesion
      requires Scc2, Scc4 for chromatin-association and Eco1/Ctf7 for conversion to a
      tethering competent state. A popular model, based on the notion that cohesins
      form huge ring-like structures, is that Scc2, Scc4 function is essential only
      during G1 such that sister chromatid cohesion results simply from DNA replisome
      passage through pre-loaded cohesin rings. In such a scenario, cohesin deposition
      during G1 is temporally uncoupled from Eco1-dependent establishment reactions
      that occur during S-phase. Chl1 DNA helicase (homolog of human ChlR1/DDX11 and
      BACH1/BRIP1/FANCJ helicases implicated in Fanconi anemia, breast and ovarian
      cancer and Warsaw Breakage Syndrome) plays a critical role in sister chromatid
      cohesion, however, the mechanism through which Chl1 promotes cohesion remains
      poorly understood. Here, we report that Chl1 promotes Scc2 loading unto DNA such
      that both Scc2 and cohesin enrichment to chromatin are defective in chl1 mutant
      cells. The results further show that both Chl1 expression and chromatin
      recruitment are tightly regulated through the cell cycle, peaking during S-phase.
      Importantly, kinetic ChIP studies reveals that Chl1 is required for Scc2
      chromatin-association specifically during S-phase, but not during G1. Despite
      normal chromatin enrichment of both Scc2 and cohesin during G1, chl1 mutant cells
      exhibit severe chromosome segregation and cohesion defects--revealing that G1
      loaded cohesins is insufficient to promote cohesion. Based on these findings, we
      propose a new model wherein S-phase cohesin loading occurs during DNA replication
      and in concert with both cohesion establishment and chromatin assembly reactions-
      challenging the notion that DNA replication fork navigates through or around pre
      loaded cohesin rings.

PMID- 24086534
TI  - Motor timing deficits in sequential movements in Parkinson disease are related to
      action planning: a motor imagery study.
AB  - Timing of sequential movements is altered in Parkinson disease (PD). Whether
      timing deficits in internally generated sequential movements in PD depends also
      on difficulties in motor planning, rather than merely on a defective ability to
      materially perform the planned movement is still undefined. To unveil this issue,
      we adopted a modified version of an established test for motor timing, i.e. the
      synchronization-continuation paradigm, by introducing a motor imagery task. Motor
      imagery is thought to involve mainly processes of movement preparation, with
      reduced involvement of end-stage movement execution-related processes. Fourteen
      patients with PD and twelve matched healthy volunteers were asked to tap in
      synchrony with a metronome cue (SYNC) and then, when the tone stopped, to keep
      tapping, trying to maintain the same rhythm (CONT-EXE) or to imagine tapping at
      the same rhythm, rather than actually performing it (CONT-MI). We tested both a
      sub-second and a supra-second inter-stimulus interval between the cues.
      Performance was recorded using a sensor-engineered glove and analyzed measuring
      the temporal error and the interval reproduction accuracy index. PD patients were
      less accurate than healthy subjects in the supra-second time reproduction task
      when performing both continuation tasks (CONT-MI and CONT-EXE), whereas no
      difference was detected in the synchronization task and on all tasks involving a
      sub-second interval. Our findings suggest that PD patients exhibit a selective
      deficit in motor timing for sequential movements that are separated by a supra
      second interval and that this deficit may be explained by a defect of motor
      planning. Further, we propose that difficulties in motor planning are of a
      sufficient degree of severity in PD to affect also the motor performance in the
      supra-second time reproduction task. 

PMID- 24086535
TI  - The mTORC2 component rictor contributes to cisplatin resistance in human ovarian
      cancer cells.
AB  - Resistance to cisplatin-based therapy is a major cause of treatment failure in
      human ovarian cancer. A better understanding of the mechanisms of cisplatin
      resistance will offer new insights for novel therapeutic strategies for this
      deadly disease. Akt and p53 are determinants of cisplatin sensitivity. Rictor is
      a component of mTOR protein kinase complex 2, which is required for Akt
      phosphorylation (Ser473) and full activation. However, the precise role of rictor
      and the relationship between rictor and p53 in cisplatin resistance remains
      poorly understood. Here, using sensitive wild-type p53 (OV2008 and A2780s),
      resistant wild-type p53 (C13* and OVCAR433), and p53 compromised (A2780cp, OCC1,
      and SKOV-3) ovarian cancer cells, we have demonstrated that (i) rictor is a
      determinant of cisplatin resistance in chemosensitive human ovarian cancer cells;
      (ii) cisplatin down-regulates rictor content by caspase-3 cleavage and
      proteasomal degradation; (iii) rictor down-regulation sensitizes chemo-resistant
      ovarian cancer cells to cisplatin-induced apoptosis in a p53-dependent manner;
      (iv) rictor suppresses cisplatin-induced apoptosis and confers resistance by
      activating and stabilizing Akt. These findings extend current knowledge on the
      molecular and cellular basis of cisplatin resistance and provide a rationale
      basis for rictor as a potential therapeutic target for chemoresistant ovarian
      cancer. 

PMID- 24086536
TI  - Mucosal vaccination with recombinant adenovirus encoding nucleoprotein provides
      potent protection against influenza virus infection.
AB  - Influenza vaccines that target the highly variable surface glycoproteins
      hemagglutinin and neuraminidase cause inconvenience of having vaccination every
      year. For this reason, development of universal vaccines targeting conserved
      viral components is needed. In this study, we generated recombinant adenovirus
      (rAd) vaccine encoding nucleoprotein (NP) of A/PR/8/34 influenza virus,
      designated rAd/NP. BALB/c mice were immunized intranasally or sublingually with
      rAd/NP vaccine and subsequently challenged with lethal doses of heterologous as
      well as homologous influenza viruses. We found that intranasal immunization of
      rAd/NP elicited strong mucosal IgA responses as well as stronger CD8 T-cell
      responses toward immunodominant K(d)-restricted NP147-155 epitope than sublingual
      immunization. Importantly, only single intranasal but not sublingual immunization
      of rAd/NP provides potent protection against both homologous and heterologous
      influenza virus challenges. These results suggest that recombinant rAd/NP could
      be a universal vaccine candidate for mucosal administration against influenza
      virus. 

PMID- 24086537
TI  - Year-round reproduction and induced spawning of Chinese amphioxus, Branchiostoma
      belcheri, in laboratory.
AB  - Amphioxus is a best candidate for studying the evolutionary and developmental
      mechanisms of vertebrates, because of its vertebrate-like but much simpler
      morphology, embryonic development and genome structure. Producing live amphioxus
      embryos throughout the year is an ideal for comparative evolution and
      developmental studies. However, all amphioxus species have distinct breeding
      seasons in the wild and laboratory. We recently found that Chinese amphioxus B.
      belcheri could reproduce repeatedly beyond its natural breeding season when
      reared under proper conditions. In this study, we were able to extend further and
      produce embryos throughout the year from October 2011 to October 2012. We found
      all examined animals had spawned repeatedly during the examined period. In
      addition, both lancelets B. belcheri and B. japonicum could be induced to spawn
      by heat-shock method, although the induced spawning efficiency was not as high as
      that observed in the European lancelet. In general, we have succeeded in
      producing B. belcheri embryos almost daily throughout the year. This advancement
      will provide essential embryonic material for evolutionary and developmental
      studies, and have great implications for the cultivation and spawning induction
      of other amphioxus species. 

PMID- 24086538
TI  - Leu452His mutation in lipoprotein lipase gene transfer associated with
      hypertriglyceridemia in mice in vivo.
AB  - Mutated mouse lipoprotein lipase (LPL) containing a leucine (L) to histidine (H)
      substitution at position 452 was transferred into mouse liver by hydrodynamics
      based gene delivery (HD). Mutated-LPL (MLPL) gene transfer significantly
      increased the concentrations of plasma MLPL and triglyceride (TG) but
      significantly decreased the activity of plasma LPL. Moreover, the gene transfer
      caused adiposis hepatica and significantly increased TG content in mouse liver.
      To understand the effects of MLPL gene transfer on energy metabolism, we
      investigated the expression of key functional genes related to energy metabolism
      in the liver, epididymal fat, and leg muscles. The mRNA contents of hormone
      sensitive lipase (HSL), adipose triglyceride lipase (ATGL), fatty acid-binding
      protein (FABP), and uncoupling protein (UCP) were found to be significantly
      reduced. Furthermore, we investigated the mechanism by which MLPL gene transfer
      affected fat deposition in the liver, fat tissue, and muscle. The gene expression
      and protein levels of forkhead Box O3 (FOXO3), AMP-activated protein kinase
      (AMPK), and peroxisome proliferator-activated receptor-gamma coactivator 1 alpha
      (PGC-1alpha) were found to be remarkably decreased in the liver, fat and muscle.
      These results suggest that the Leu452His mutation caused LPL dysfunction and gene
      transfer of MLPL in vivo produced resistance to the AMPK/PGC-1alpha signaling
      pathway in mice. 

PMID- 24086539
TI  - Enu mutagenesis identifies a novel platelet phenotype in a loss-of-function Jak2
      allele.
AB  - Utilizing ENU mutagenesis, we identified a mutant mouse with elevated platelets.
      Genetic mapping localized the mutation to an interval on chromosome 19 that
      encodes the Jak2 tyrosine kinase. We identified a A3056T mutation resulting in a
      premature stop codon within exon 19 of Jak2 (Jak2(K915X)), resulting in a protein
      truncation and functionally inactive enzyme. This novel platelet phenotype was
      also observed in mice bearing a hemizygous targeted disruption of the Jak2 locus
      (Jak2(+/-)). Timed pregnancy experiments revealed that Jak2(K915X/K915X) and
      Jak2(-/-) displayed embryonic lethality; however, Jak2(K915X/K915X) embryos were
      viable an additional two days compared to Jak2(-/-) embryos. Our data suggest
      that perturbing JAK2 activation may have unexpected consequences in elevation of
      platelet number and correspondingly, important implications for treatment of
      hematological disorders with constitutive Jak2 activity.

PMID- 24086540
TI  - Gastric inhibitory polypeptide receptor methylation in newly diagnosed, drug
      naive patients with type 2 diabetes: a case-control study.
AB  - GIP action in type 2 diabetic (T2D) patients is altered. We hypothesized that
      methylation changes could be present in GIP receptor of T2D patients. This study
      aimed to assess the differences in DNA methylation profile of GIPR promoter
      between T2D patients and age- and Body Mass Index (BMI)-matched controls. We
      included 93 T2D patients (cases) that were uniquely on diet (without any anti
      diabetic pharmacological treatment). We matched one control (with oral glucose
      tolerance test negative, non diabetic), by age and BMI, for every case. Cytokines
      and hormones were determined by ELISA. DNA was extracted from whole blood and DNA
      methylation was assessed using the Sequenom EpiTYPER system. Our results showed
      that T2D patients were more insulin resistant and had a poorer beta cell function
      than their controls. Fasting adiponectin was lower in T2D patients as compared to
      controls (7.0+/-3.8 ugr/mL vs. 10.0+/-4.2 ugr/mL). Levels of IL 12 in serum were
      almost double in T2D patients (52.8+/-58.3 pg/mL vs. 29.7+/-37.4 pg/mL). We found
      that GIPR promoter was hypomethylated in T2D patients as compared to controls. In
      addition, HOMA-IR and fasting glucose correlated negatively with mean methylation
      of GIPR promoter, especially in T2D patients. This case-control study confirms
      that newly diagnosed, drug-naive T2D patients are more insulin resistant and have
      worse beta cell function than age- and BMI-matched controls, which is partly
      related to changes in the insulin-sensitizing metabolites (adiponectin), in the
      proinflammatory profile (IL12) and we suggest in the methylation pattern of GIPR.
      Our study provides novel findings on GIPR promoter methylation profile which may
      improve our ability to understand type 2 diabetes pathogenesis. 

PMID- 24086541
TI  - Community health workers and health care delivery: evaluation of a women's
      reproductive health care project in a developing country.
AB  - BACKGROUND: As part of the mid-term evaluation of a Women's Health Care Project,
      a study was conducted to compare the utilization of maternal and neonatal health
      (MNH) services in two areas with different levels of service in Punjab, Pakistan.
      METHODS: A cross-sectional survey was conducted to interview Married Women of
      Reproductive Age (MWRA). Information was collected on MWRA knowledge regarding
      danger signs during pregnancy, delivery, postnatal periods, and MNH care seeking
      behavior. After comparing MNH service utilization, the two areas were compared
      using a logistic regression model, to identify the association of different
      factors with the intervention after controlling for socio-demographic, economic
      factors and distance of the MWRA residence to a health care facility. RESULTS:
      The demographic characteristics of women in the two areas were similar, although
      socioeconomic status as indicated by level of education and better household
      amenities, was higher in the intervention area. Consequently, on univariate
      analysis, utilization of MNH services: antenatal care, TT vaccination,
      institutional delivery and use of modern contraceptives were higher in the
      intervention than control area. Nonetheless, multivariable analysis controlling
      for confounders such as socioeconomic status revealed that utilization of
      antenatal care services at health centers and TT vaccination during pregnancy are
      significantly associated with the intervention. CONCLUSIONS: Our findings suggest
      positive changes in health care seeking behavior of women and families with
      respect to MNH. Some aspects of care still require attention, such as knowledge
      about danger signs and neonatal care, especially umbilical cord care. Despite
      overall success achieved so far in response to the Millennium Development Goals,
      over the past two decades decreases in maternal mortality are far from the 2015
      target. This report identifies some of the key factors to improving MNH and
      serves as an interim measure of a national and global challenge that remains a
      work in progress.

PMID- 24086542
TI  - Simvastatin enhances protection against Listeria monocytogenes infection in mice
      by counteracting Listeria-induced phagosomal escape.
AB  - Statins are well-known cholesterol lowering drugs targeting HMG-CoA-reductase,
      reducing the risk of coronary disorders and hypercholesterolemia. Statins are
      also involved in immunomodulation, which might influence the outcome of bacterial
      infection. Hence, a possible effect of statin treatment on Listeriosis was
      explored in mice. Statin treatment prior to subsequent L. monocytogenes infection
      strikingly reduced bacterial burden in liver and spleen (up to 100-fold) and
      reduced histopathological lesions. Statin-treatment in infected macrophages
      resulted in increased IL-12p40 and TNF-alpha and up to 4-fold reduced bacterial
      burden within 6 hours post infection, demonstrating a direct effect of statins on
      limiting bacterial growth in macrophages. Bacterial uptake was normal
      investigated in microbeads and GFP-expressing Listeria experiments by confocal
      microscopy. However, intracellular membrane-bound cholesterol level was
      decreased, as analyzed by cholesterol-dependent filipin staining and cellular
      lipid extraction. Mevalonate supplementation restored statin-inhibited
      cholesterol biosynthesis and reverted bacterial growth in Listeria monocytogenes
      but not in listeriolysin O (LLO)-deficient Listeria. Together, these results
      suggest that statin pretreatment increases protection against L. monocytogenes
      infection by reducing membrane cholesterol in macrophages and thereby preventing
      effectivity of the cholesterol-dependent LLO-mediated phagosomal escape of
      bacteria. 

PMID- 24086543
TI  - Cytochrome P450 CYP1B1 interacts with 8-methoxypsoralen (8-MOP) and influences
      psoralen-ultraviolet A (PUVA) sensitivity.
AB  - BACKGROUND: There are unpredictable inter-individual differences in sensitivity
      to psoralen-UVA (PUVA) photochemotherapy, used to treat skin diseases including
      psoriasis. Psoralens are metabolised by cytochrome P450 enzymes (P450), and we
      hypothesised that variability in cutaneous P450 expression may influence PUVA
      sensitivity. We previously showed that P450 CYP1B1 was abundantly expressed in
      human skin and regulated by PUVA, and described marked inter-individual
      differences in cutaneous CYP1B1 expression. OBJECTIVES: We investigated whether
      CYP1B1 made a significant contribution to 8-methoxypsoralen (8-MOP) metabolism,
      and whether individuality in CYP1B1 activity influenced PUVA sensitivity.
      METHODS: We used E. coli membranes co-expressing various P450s and cytochrome
      P450 reductase (CPR) to study 8-MOP metabolism and cytotoxicity assays in CYP1B1
      expressing mammalian cells to assess PUVA sensitivity. RESULTS: We showed that
      P450s CYP1A1, CYP1A2, CYP1B1, CYP2A6 and CYP2E1 influence 8-MOP metabolism. As
      CYP1B1 is the most abundant P450 in human skin, we further demonstrated that: (i)
      CYP1B1 interacts with 8-MOP (ii) metabolism of the CYP1B1 substrates 7
      ethoxyresorufin and 17-beta-estradiol showed concentration-dependent inhibition
      by 8-MOP and (iii) inhibition of 7-ethoxyresorufin metabolism by 8-MOP was
      influenced by CYP1B1 genotype. The influence of CYP1B1 on PUVA cytotoxicity was
      further investigated in a Chinese hamster ovary cell line, stably expressing
      CYP1B1 and CPR, which was more sensitive to PUVA than control cells, suggesting
      that CYP1B1 metabolises 8-MOP to a more phototoxic metabolite(s). CONCLUSION: Our
      data therefore suggest that CYP1B1 significantly contributes to cutaneous 8-MOP
      metabolism, and that individuality in CYP1B1 expression may influence PUVA
      sensitivity.

PMID- 24086544
TI  - Low-density lipoprotein receptor related protein-1 (LRP1)-dependent cell
      signaling promotes neurotrophic activity in embryonic sensory neurons.
AB  - Developing sensory neurons require neurotrophic support for survival, neurite
      outgrowth and myelination. The low-density lipoprotein receptor-related protein-1
      (LRP1) transactivates Trk receptors and thereby functions as a putative
      neurotrophin. Herein, we show that LRP1 is abundantly expressed in developing
      dorsal root ganglia (DRG) and that LRP1-dependent cell signaling supports
      survival, neurite extension and receptivity to Schwann cells even in the absence
      of neurotrophins. Cultured embryonic DRG neurons (E15) were treated with
      previously characterized LRP1 ligands, LRP1-receptor binding domain of alpha2
      macroglobulin (RBD), hemopexin domain of MMP-9 (PEX) or controls (GST) for two
      weeks. These structurally diverse LRP1 ligands significantly activated and
      sustained extracellular signal-regulated kinases (ERK1/2) 5-fold (p<0.05),
      increased expression of growth-associated protein-43(GAP43) 15-fold (P<0.01), and
      increased neurite outgrowth 20-fold (P<0.01). Primary sensory neurons treated
      with LRP1 ligands survived > 2 weeks in vitro, to an extent equaling NGF, a
      finding associated with canonical signaling mechanisms and blockade of caspase-3
      cleavage. LRP1 ligand-induced survival and sprouting were blocked by co
      incubation with the LRP1 antagonist, receptor associated protein (RAP), whereas
      RAP had no effect on NGF-induced activity. Site directed mutagenesis of the LRP1
      ligand, RBD, in which Lys(1370) and Lys(1374) are converted to alanine to
      preclude LRP1 binding, were ineffective in promoting cell signaling, survival or
      inducing neurite extension in primary sensory neurons, confirming LRP1
      specificity. Furthermore, LRP1-induced neurite sprouting was mediated by Src
      family kinase (SFK) activation, suggesting transactivation of Trk receptors. Co
      cultures of primary embryonic neurons and Schwann cells showed that LRP1 agonists
      promoted axonal receptivity to myelination to Schwann cells. Collectively, these
      findings identify LRP1 as a novel and perhaps essential trophic molecule for
      sensory neuronal survival and development. 

PMID- 24086545
TI  - IL-1Beta enriched monocytes mount massive IL-6 responses to common inflammatory
      triggers among chronically HIV-1 infected adults on stable anti-retroviral
      therapy at risk for cardiovascular disease.
AB  - Chronic infection by HIV increases the risk of cardiovascular disease (CVD)
      despite effective antiretroviral therapy (ART). The mechanisms linking HIV to CVD
      have yet to be fully elucidated. High plasma levels of the pro-inflammatory
      cytokine IL-6, which may be triggered by IL-1beta, is a biomarker of CVD risk in
      HIV-negative adults, and of all-cause mortality in HIV disease. Monocytes play a
      pivotal role in atherosclerosis, and may be major mediators of HIV-associated
      inflammation. We therefore hypothesized that monocytes from HIV-infected adults
      would display high inflammatory responses. Employing a 10-color flow cytometry
      intracellular cytokine staining assay, we directly assessed cytokine and
      chemokine responses of monocytes from the cryopreserved peripheral blood of 33
      chronically HIV-1 infected subjects. Participants were 45 years or older, on
      virologically suppressive ART and at risk for CVD. This group was compared to 14
      HIV-negative subjects matched for age and gender, with similar CVD risk. We
      simultaneously detected intracellular expression of IL-1beta, IL-6, IL-8 and TNF
      in blood monocytes in the basal state and after stimulation by triggers commonly
      found in the blood of treated, chronically HIV-infected subjects:
      lipopolysaccharide (LPS) and oxidized low-density lipoprotein (oxLDL). In the
      absence of stimulation, monocytes from treated HIV-infected subjects displayed a
      high frequency of cells producing IL-1beta (median 19.5%), compared to low levels
      in HIV-uninfected persons (0.9% p<0.0001). IL-8, which is induced by IL-1beta,
      was also highly expressed in the HIV-infected group in the absence of
      stimulation, 43.7% compared to 1.9% in HIV-uninfected subjects, p<0.0001.
      Strikingly, high basal expression of IL-1beta by monocytes predicted high IL-6
      levels in the plasma, and high monocyte IL-6 responses in HIV-infected subjects.
      Hyper-inflammatory IL-1beta enriched monocytes may be a major source of IL-6
      production and systemic inflammation in HIV-infected adults, and may contribute
      to the risk for all-cause mortality and cardiovascular disease in treated HIV
      infection. 

PMID- 24086547
TI  - Comparing memory-efficient genome assemblers on stand-alone and cloud
      infrastructures.
AB  - A fundamental problem in bioinformatics is genome assembly. Next-generation
      sequencing (NGS) technologies produce large volumes of fragmented genome reads,
      which require large amounts of memory to assemble the complete genome
      efficiently. With recent improvements in DNA sequencing technologies, it is
      expected that the memory footprint required for the assembly process will
      increase dramatically and will emerge as a limiting factor in processing widely
      available NGS-generated reads. In this report, we compare current memory
      efficient techniques for genome assembly with respect to quality, memory
      consumption and execution time. Our experiments prove that it is possible to
      generate draft assemblies of reasonable quality on conventional multi-purpose
      computers with very limited available memory by choosing suitable assembly
      methods. Our study reveals the minimum memory requirements for different assembly
      programs even when data volume exceeds memory capacity by orders of magnitude. By
      combining existing methodologies, we propose two general assembly strategies that
      can improve short-read assembly approaches and result in reduction of the memory
      footprint. Finally, we discuss the possibility of utilizing cloud infrastructures
      for genome assembly and we comment on some findings regarding suitable
      computational resources for assembly. 

PMID- 24086548
TI  - Alterations of white matter integrity related to the season of birth in
      schizophrenia: a DTI study.
AB  - In schizophrenia there is a consistent epidemiological finding of a birth excess
      in winter and spring. Season of birth is thought to act as a proxy indicator for
      harmful environmental factors during foetal maturation. There is evidence that
      prenatal exposure to harmful environmental factors may trigger pathologic
      processes in the neurodevelopment, which subsequently increase the risk of
      schizophrenia. Since brain white matter alterations have repeatedly been found in
      schizophrenia, the objective of this study was to investigate whether white
      matter integrity was related to the season of birth in patients with
      schizophrenia. Thirty-four patients with schizophrenia and 33 healthy controls
      underwent diffusion tensor imaging. Differences in the fractional anisotropy maps
      of schizophrenia patients and healthy controls born in different seasons were
      analysed with tract-based spatial statistics. A significant main effect of season
      of birth and an interaction of group and season of birth showed that patients
      born in summer had significantly lower fractional anisotropy in widespread white
      matter regions than those born in the remainder of the year. Additionally, later
      age of schizophrenia onset was found in patients born in winter months. The
      current findings indicate a relationship of season of birth and white matter
      alterations in schizophrenia and consequently support the neurodevelopmental
      hypothesis of early pathological mechanisms in schizophrenia. 

PMID- 24086546
TI  - Bions: a family of biomimetic mineralo-organic complexes derived from biological
      fluids.
AB  - Mineralo-organic nanoparticles form spontaneously in human body fluids when the
      concentrations of calcium and phosphate ions exceed saturation. We have shown
      previously that these mineralo-organic nanoparticles possess biomimetic
      properties and can reproduce the whole phenomenology of the so-called
      nanobacteria-mineralized entities initially described as the smallest
      microorganisms on earth. Here, we examine the possibility that various charged
      elements and ions may form mineral nanoparticles with similar properties in
      biological fluids. Remarkably, all the elements tested, including sodium,
      magnesium, aluminum, calcium, manganese, iron, cobalt, nickel, copper, zinc,
      strontium, and barium form mineralo-organic particles with bacteria-like
      morphologies and other complex shapes following precipitation with phosphate in
      body fluids. Upon formation, these mineralo-organic particles, which we term
      bions, invariably accumulate carbonate apatite during incubation in biological
      fluids; yet, the particles also incorporate additional elements and thus reflect
      the ionic milieu in which they form. Bions initially harbor an amorphous mineral
      phase that gradually converts to crystals in culture. Our results show that serum
      produces a dual inhibition-seeding effect on bion formation. Using a
      comprehensive proteomic analysis, we identify a wide range of proteins that bind
      to these mineral particles during incubation in medium containing serum. The two
      main binding proteins identified, albumin and fetuin-A, act as both inhibitors
      and seeders of bions in culture. Notably, bions possess several biomimetic
      properties, including the possibility to increase in size and number and to be
      sub-cultured in fresh culture medium. Based on these results, we propose that
      bions represent biological, mineralo-organic particles that may form in the body
      under both physiological and pathological homeostasis conditions. These mineralo
      organic particles may be part of a physiological cycle that regulates the
      function, transport and disposal of elements and minerals in the human body. 

PMID- 24086549
TI  - Air pollution and newly diagnostic autism spectrum disorders: a population-based
      cohort study in Taiwan.
AB  - There is limited evidence that long-term exposure to ambient air pollution
      increases the risk of childhood autism spectrum disorder (ASD). The objective of
      the study was to investigate the associations between long-term exposure to air
      pollution and newly diagnostic ASD in Taiwan. We conducted a population-based
      cohort of 49,073 children age less than 3 years in 2000 that were retrieved from
      Taiwan National Insurance Research Database and followed up from 2000 through
      2010. Inverse distance weighting method was used to form exposure parameter for
      ozone (O3), carbon monoxide (CO), nitrogen dioxide (NO2), sulfur dioxide (SO2),
      and particles with aerodynamic diameter less than 10 um (PM10). Time-dependent
      Cox proportional hazards (PH) model was performed to evaluate the relationship
      between yearly average exposure air pollutants of preceding years and newly
      diagnostic ASD. The risk of newly diagnostic ASD increased according to
      increasing O3, CO, NO2, and SO2 levels. The effect estimate indicating an
      approximately 59% risk increase per 10 ppb increase in O3 level (95% CI 1.42
      1.79), 37% risk increase per 10 ppb in CO (95% CI 1.31-1.44), 340% risk increase
      per 10 ppb increase in NO2 level (95% CI 3.31-5.85), and 17% risk increase per 1
      ppb in SO2 level (95% CI 1.09-1.27) was stable with different combinations of air
      pollutants in the multi-pollutant models. Our results provide evident that
      children exposure to O3, CO, NO2, and SO2 in the preceding 1 year to 4 years may
      increase the risk of ASD diagnosis. 

PMID- 24086550
TI  - Serum estradiol and testosterone levels in kidney stones disease with and without
      calcium oxalate components in naturally postmenopausal women.
AB  - OBJECTIVE: Epidemiological data reveal that the overall risk for kidney stones
      disease is lower for women compared to age-matched men. However, the beneficial
      effect for the female sex is lost upon menopause, a time corresponding to the
      onset of fall in estrogen levels. The aim of this study was to describe the serum
      estradiol (E2) and testosterone (T) characteristics of naturally postmenopausal
      women with kidney stones. METHODS: 113 naturally postmenopausal women with newly
      diagnosed kidney stones (aged 57.4+/-4.98 years) and 84 age frequency matched
      stone-free controls (56.9+/-4.56 years) were validly recruited in the case
      control study. The odds ratios (ORs) for the associations between sex hormones
      and kidney stones were estimated with logistic regression models, adjusting for
      demographic data and medical history. Patients were also stratified analyzed
      according to stone components (calcium oxalate stones [COS]; non-calcium oxalate
      stones [NCOS]). RESULTS: Serum E2 (21.1 vs. 31.1 pg/ml) was significantly lower
      in kidney stones patients compared to controls. Post-hoc analysis demonstrated
      that this effect was driven by COS patients (p<0.001). According to tertiles of
      the E2 levels, a significant higher frequency of COS was seen in the lowest E2
      group (p <0.001). Multiple logistic regression analysis identified E2 level as a
      strong factor that was independently associated with the risk for COS (per 1 SD
      increase, OR=0.951, 95% confidence interval [CI] = 0.919-0.985; highest: lowest
      tertile, OR=0.214, 95%CI = 0.069-0.665). However, serum T levels did not
      significantly differ among the groups. CONCLUSIONS: Naturally postmenopausal
      women with higher remaining estradiol levels appear less likely to suffer from
      kidney calcium oxalate stones. However, no correlation was found between serum T
      level and kidney stones. These findings support the hypothesis that higher
      postmenopausal endogenous estrogens may protect against kidney stones with
      ageing.

PMID- 24086551
TI  - Identification of an enhancer that increases miR-200b~200a~429 gene expression in
      breast cancer cells.
AB  - The miR-200b~200a~429 gene cluster is a key regulator of EMT and cancer
      metastasis, however the transcription-based mechanisms controlling its expression
      during this process are not well understood. We have analyzed the miR
      200b~200a~429 locus for epigenetic modifications in breast epithelial and
      mesenchymal cell lines using chromatin immunoprecipitation assays and DNA
      methylation analysis. We discovered a novel enhancer located approximately 5.1kb
      upstream of the miR-200b~200a~429 transcriptional start site. This region was
      associated with the active enhancer chromatin signature comprising H3K4me1,
      H3K27ac, RNA polymerase II and CpG dinucleotide hypomethylation. Luciferase
      reporter assays revealed the upstream enhancer stimulated the transcription of
      the miR-200b~200a~429 minimal promoter region approximately 27-fold in breast
      epithelial cells. Furthermore, we found that a region of the enhancer was
      transcribed, producing a short, GC-rich, mainly nuclear, non-polyadenylated RNA
      transcript designated miR-200b eRNA. Over-expression of miR-200b eRNA had little
      effect on miR-200b~200a~429 promoter activity and its production did not
      correlate with miR-200b~200a~429 gene expression. While additional investigations
      of miR-200b eRNA function will be necessary, it is possible that miR-200b eRNA
      may be involved in the regulation of miR-200b~200a~429 gene expression and
      silencing. Taken together, these findings reveal the presence of a novel
      enhancer, which contributes to miR-200b~200a~429 transcriptional regulation in
      epithelial cells. 

PMID- 24086552
TI  - Systematic review of anastomotic leakage rate according to an international
      grading system following anterior resection for rectal cancer.
AB  - BACKGROUND: A generally acceptable definition and a severity grading system for
      anastomotic leakages (ALs) following rectal resection were not available until
      2010, when the International Study Group of Rectal Cancer (ISGRC) proposed a
      definition and a grading system for AL. METHODS: A search for published data was
      performed using the MEDLINE database (2000 to December 5, 2012) to perform a
      systematic review of the studies that described AL, grade AL according to the
      grading system, pool data, and determine the average rate of AL for each grade
      after anterior resection (AR) for rectal cancer. RESULTS: A total of 930
      abstracts were retrieved; 40 articles on AR, 25 articles on low AR (LAR), and 5
      articles on ultralow AR (ULAR) were included in the review and analysis. The
      pooled overall AL rate of AR was 8.58% (2,085/24,288); the rate of the
      asymptomatic leakage (Grade A) was 2.57%, that of AL that required active
      intervention without relaparotomy (Grade B) was 2.37%, and that of AL that
      required relaparotomy (Grade C) was 5.40%. The pooled rate of AL that required
      relaparotomy was higher in AR (5.40%) than in LAR (4.70%) and in ULAR (1.81%),
      which could be attributed to the higher rate of protective defunctioning stoma in
      LAR (40.72%) and ULAR (63.44%) compared with that in AR (30.11%). CONCLUSIONS:
      The new grading system is simple that the ALs of each grade can be easily
      extracted from past publications, therefore likely to be accepted and applied in
      future studies.

PMID- 24086553
TI  - The prevalence and polymorphisms of zonula occluden toxin gene in multiple
      Campylobacter concisus strains isolated from saliva of patients with inflammatory
      bowel disease and controls.
AB  - Campylobacterconcisus is an oral bacterium. A number of studies detected a
      significantly higher prevalence of C. concisus in the intestinal tract of
      patients with inflammatory bowel disease (IBD) as compared to controls. The
      prevalence of zonula occluden toxin (zot) gene, which encodes a toxin known to
      increase intestinal permeability, in oral C. concisus strains is unknown.
      Increased intestinal permeability is a feature of IBD. A total of 56 oral C.
      concisus strains isolated from 19 patients with IBD and 20 controls were examined
      (some individuals were colonized with multiple strains). A filtration method was
      used for isolation of C. concisus from saliva samples. SDS-PAGE was used to
      define strains. PCR was used to amplify zot from C. concisus strains. Positive
      PCR products were sequenced and the nucleotides and amino acids were compared. Of
      the 56 oral C. concisus strains examined, 17 strains (30.4%) were positive for
      zot. The prevalence of zot-positive oral C. concisus strains was 54.5% in
      patients with active IBD, which was not significantly different from that in
      healthy controls (40%). Polymorphisms of C. concisus zot were revealed. zot
      (808T) , zot (350-351AC) and zot (Multiple) were detected only in patients with
      IBD, but not in healthy controls. Both zot (808T) and zot (Multiple) alleles
      resulted in substitution of valine at position 270, which occurred in 36.4% of
      patients with active IBD but not in healthy controls (P = 0.011). Furthermore,
      the prevalence of multiple oral C. concisus strains in patients with active IBD
      was significantly higher than that in healthy controls (P = 0.013). This is the
      first study reporting the prevalence of zot in human oral C. concisus strains and
      the polymorphisms of C. concisus zot gene. The data suggest that the possible
      role of C. concisus strains containing specific polymorphic forms of zot gene in
      human IBD should be investigated. 

PMID- 24086554
TI  - Febuxostat, an inhibitor of xanthine oxidase, suppresses lipopolysaccharide
      induced MCP-1 production via MAPK phosphatase-1-mediated inactivation of JNK.
AB  - Excess reactive oxygen species (ROS) formation can trigger various pathological
      conditions such as inflammation, in which xanthine oxidase (XO) is one major
      enzymatic source of ROS. Although XO has been reported to play essential roles in
      inflammatory conditions, the molecular mechanisms underlying the involvement of
      XO in inflammatory pathways remain unclear. Febuxostat, a selective and potent
      inhibitor of XO, effectively inhibits not only the generation of uric acid but
      also the formation of ROS. In this study, therefore, we examined the effects of
      febuxostat on lipopolysaccharide (LPS)-mediated inflammatory responses. Here we
      show that febuxostat suppresses LPS-induced MCP-1 production and mRNA expression
      via activating MAPK phosphatase-1 (MKP-1) which, in turn, leads to
      dephosphorylation and inactivation of JNK in macrophages. Moreover, these effects
      of febuxostat are mediated by inhibiting XO-mediated intracellular ROS
      production. Taken together, our data suggest that XO mediates LPS-induced
      phosphorylation of JNK through ROS production and MKP-1 inactivation, leading to
      MCP-1 production in macrophages. These studies may bring new insights into the
      novel role of XO in regulating inflammatory process through MAPK phosphatase, and
      demonstrate the potential use of XO inhibitor in modulating the inflammatory
      processes. 

PMID- 24086555
TI  - A risk prediction score for invasive mold disease in patients with hematological
      malignancies.
AB  - BACKGROUND: A risk score for invasive mold disease (IMD) in patients with
      hematological malignancies could facilitate patient screening and improve the
      targeted use of antifungal prophylaxis. METHODS: We retrospectively analyzed
      1,709 hospital admissions of 840 patients with hematological malignancies (2005
      2008) to collect data on 17 epidemiological and treatment-related risk factors
      for IMD. Multivariate regression was used to develop a weighted risk score based
      on independent risk factors associated with proven or probable IMD, which was
      prospectively validated during 1,746 hospital admissions of 855 patients from
      2009-2012. RESULTS: Of the 17 candidate variables analyzed, 11 correlated with
      IMD by univariate analysis, but only 4 risk factors (neutropenia, lymphocytopenia
      or lymphocyte dysfunction in allogeneic hematopoietic stem cell transplant
      recipients, malignancy status, and prior IMD) were retained in the final
      multivariate model, resulting in a weighted risk score 0-13. A risk score of < 6
      discriminated patients with low (< 1%) versus higher incidence rates (> 5%) of
      IMD, with a negative predictive value (NPV) of 0.99, (95% CI 0.98-0.99). During
      2009-2012, patients with a calculated risk score at admission of < 6 had
      significantly lower 90-day incidence rates of IMD compared to patients with
      scores > 6 (0.9% vs. 10.6%, P <0.001). CONCLUSION: An objective, weighted risk
      score for IMD can accurately discriminate patients with hematological
      malignancies at low risk for developing mold disease, and could possibly
      facilitate "screening-out" of low risk patients less likely to benefit from
      intensive diagnostic monitoring or mold-directed antifungal prophylaxis.

PMID- 24086556
TI  - Microglial cells are involved in the susceptibility of NADPH oxidase knockout
      mice to 6-hydroxy-dopamine-induced neurodegeneration.
AB  - We explored the impact of Nox-2 in modulating inflammatory-mediated microglial
      responses in the 6-hydroxydopamine (6-OHDA)-induced Parkinson's disease (PD)
      model. Nox1 and Nox2 gene expression were found to increase in striatum, whereas
      a marked increase of Nox2 expression was observed in substantia nigra (SN) of
      wild-type (wt) mice after PD induction. Gp91(phox-/-) 6-OHDA-lesioned mice
      exhibited a significant reduction in the apomorphine-induced rotational behavior,
      when compared to wt mice. Immunolabeling assays indicated that striatal 6-OHDA
      injections reduced the number of dopaminergic (DA) neurons in the SN of wt mice.
      In gp91(phox-/-) 6-OHDA-lesioned mice the DA degeneration was negligible,
      suggesting an involvement of Nox in 6-OHDA-mediated SN degeneration. Gp91(phox-/
      ) 6-OHDA-lesioned mice treated with minocycline, a tetracycline derivative that
      exerts multiple anti-inflammatory effects, including microglial inhibition,
      exhibited increased apomorphine-induced rotational behavior and degeneration of
      DA neurons after 6-OHDA injections. The same treatment also increased TNF-alpha
      release and potentiated NF-kappaB activation in the SN of gp91(phox-/-)-lesioned
      mice. Our results demonstrate for the first time that inhibition of microglial
      cells increases the susceptibility of gp91(phox-/-) 6-OHDA lesioned mice to
      develop PD. Blockade of microglia leads to NF-kappaB activation and TNF-alpha
      release into the SN of gp91(phox-/-) 6-OHDA lesioned mice, a likely mechanism
      whereby gp91(phox-/-) 6-OHDA lesioned mice may be more susceptible to develop PD
      after microglial cell inhibition. Nox2 adds an essential level of regulation to
      signaling pathways underlying the inflammatory response after PD induction. 

PMID- 24086557
TI  - Development and application of stable phantoms for the evaluation of
      photoacoustic imaging instruments.
AB  - Photoacoustic imaging combines the high contrast of optical imaging with the
      spatial resolution and penetration depth of ultrasound. This technique holds
      tremendous potential for imaging in small animals and importantly, is clinically
      translatable. At present, there is no accepted standard physical phantom that can
      be used to provide routine quality control and performance evaluation of
      photoacoustic imaging instruments. With the growing popularity of the technique
      and the advent of several commercial small animal imaging systems, it is
      important to develop a strategy for assessment of such instruments. Here, we
      developed a protocol for fabrication of physical phantoms for photoacoustic
      imaging from polyvinyl chloride plastisol (PVCP). Using this material, we
      designed and constructed a range of phantoms by tuning the optical properties of
      the background matrix and embedding spherical absorbing targets of the same
      material at different depths. We created specific designs to enable: routine
      quality control; the testing of robustness of photoacoustic signals as a function
      of background; and the evaluation of the maximum imaging depth available.
      Furthermore, we demonstrated that we could, for the first time, evaluate two
      small animal photoacoustic imaging systems with distinctly different light
      delivery, ultrasound imaging geometries and center frequencies, using stable
      physical phantoms and directly compare the results from both systems. 

PMID- 24086558
TI  - Cj1411c encodes for a cytochrome P450 involved in Campylobacter jejuni 81-176
      pathogenicity.
AB  - Cytochrome P450s are b-heme-containing enzymes that are able to introduce oxygen
      atoms into a wide variety of organic substrates. They are extremely widespread in
      nature having diverse functions at both biochemical and physiological level. The
      genome of C. jejuni 81-176 encodes a single cytochrome P450 (Cj1411c) that has no
      close homologues. Cj1411c is unusual in its genomic location within a cluster
      involved in the biosynthesis of outer surface structures. Here we show that E.
      coli expressed and affinity-purified C. jejuni cytochrome P450 is lipophilic,
      containing one equivalent Cys-ligated heme. Immunoblotting confirmed the
      association of cytochrome P450 with membrane fractions. A Cj1411c deletion mutant
      had significantly reduced ability to infect human cells and was less able to
      survive following exposure to human serum when compared to the wild type strain.
      Phenotypically following staining with Alcian blue, we show that a Cj1411c
      deletion mutant produces significantly less capsular polysaccharide. This study
      describes the first known membrane-bound bacterial cytochrome P450 and its
      involvement in Campylobacter virulence. 

PMID- 24086559
TI  - Microfabricated polyacrylamide devices for the controlled culture of growing
      cells and developing organisms.
AB  - The ability to spatially confine living cells or small organisms while
      dynamically controlling their aqueous environment is important for a host of
      microscopy applications. Here, we show how polyacrylamide layers can be patterned
      to construct simple microfluidic devices for this purpose. We find that
      polyacrylamide gels can be molded like PDMS into micron-scale structures that can
      enclose organisms, while being permeable to liquids, and transparent to allow for
      microscopic observation. We present a range of chemostat-like devices to observe
      bacterial and yeast growth, and C. elegans nematode development. The devices can
      integrate PDMS layers and allow for temporal control of nutrient conditions and
      the presence of drugs on a minute timescale. We show how spatial confinement of
      motile C. elegans enables for time-lapse microscopy in a parallel fashion. 

PMID- 24086561
TI  - Dynamic evolution of rht-1 homologous regions in grass genomes.
AB  - Hexaploid bread wheat contains A, B, and D three subgenomes with its well
      characterized ancestral genomes existed at diploid and tetraploid levels, making
      the wheat act as a good model species for studying evolutionary genomic dynamics.
      Here, we performed intra- and inter-species comparative analyses of wheat and
      related grass genomes to examine the dynamics of homologous regions surrounding
      Rht-1, a well-known "green revolution" gene. Our results showed that the
      divergence of the two A genomes in the Rht-1 region from the diploid and
      tetraploid species is greater than that from the tetraploid and hexaploid wheat.
      The divergence of D genome between diploid and hexaploid is lower than those of A
      genome, suggesting that D genome diverged latter than others. The divergence
      among the A, B and D subgenomes was larger than that among different ploidy
      levels for each subgenome which mainly resulted from genomic structural variation
      of insertions and, perhaps deletions, of the repetitive sequences. Meanwhile, the
      repetitive sequences caused genome expansion further after the divergence of the
      three subgenomes. However, several conserved non-coding sequences were identified
      to be shared among the three subgenomes of wheat, suggesting that they may have
      played an important role to maintain the homolog of three subgenomes. This is a
      pilot study on evolutionary dynamics across the wheat ploids, subgenomes and
      differently related grasses. Our results gained new insights into evolutionary
      dynamics of Rht-1 region at sequence level as well as the evolution of wheat
      during the plolyploidization process. 

PMID- 24086560
TI  - Spinal actions of lipoxin A4 and 17(R)-resolvin D1 attenuate inflammation-induced
      mechanical hypersensitivity and spinal TNF release.
AB  - Lipoxins and resolvins have anti-inflammatory and pro-resolving actions and
      accumulating evidence indicates that these lipid mediators also attenuate pain
      like behavior in a number of experimental models of inflammation and tissue
      injury-induced pain. The present study was undertaken to assess if spinal
      administration of lipoxin A4 (LXA4) or 17 (R)-resolvin D1 (17(R)-RvD1) attenuates
      mechanical hypersensitivity in the carrageenan model of peripheral inflammation
      in the rat. Given the emerging role of spinal cytokines in the generation and
      maintenance of inflammatory pain we measured cytokine levels in the cerebrospinal
      fluid (CSF) after LXA4 or 17(R)-RvD1 administration, and the ability of these
      lipid metabolites to prevent stimuli-induced release of cytokines from cultured
      primary spinal astrocytes. We found that intrathecal bolus injection of LXA4
      and17(R)-RvD1 attenuated inflammation-induced mechanical hypersensitivity without
      reducing the local inflammation. Furthermore, both LXA4 and 17(R)-RvD1 reduced
      carrageenan-induced tumor necrosis factor (TNF) release in the CSF, while only
      17(R)-RvD1attenuated LPS and IFN-gamma-induced TNF release in astrocyte cell
      culture. In conclusion, this study demonstrates that lipoxins and resolvins
      potently suppress inflammation-induced mechanical hypersensitivity, possibly by
      attenuating cytokine release from spinal astrocytes. The inhibitory effect of
      lipoxins and resolvins on spinal nociceptive processing puts them in an
      intriguing position in the search for novel pain therapeutics. 

PMID- 24086562
TI  - Monosodium glutamate (MSG) consumption is associated with urolithiasis and
      urinary tract obstruction in rats.
AB  - BACKGROUND: The peritoneal injection of monosodium glutamate (MSG) can induce
      kidney injury in adult rats but the effects of long-term oral intake have not
      been determined. METHODS: We investigated the kidney histology and function in
      adult male Wistar rats that were fed ad libitum with a standard rat chow pellet
      and water with or without the addition of 2 mg/g body weight MSG/day in drinking
      water (n=10 per group). Both MSG-treated and control animals were sacrificed
      after 9 months when renal function parameters, blood and urine electrolytes, and
      tissue histopathology were determined. RESULTS: MSG-treated rats were more prone
      to kidney stone formation, as represented by the alkaline urine and significantly
      higher activity product of calcium phosphate. Accordingly, 3/10 MSG-treated rats
      developed kidney stones over 9 months versus none of the control animals.
      Further, 2/10 MSG-treated rats but none (0/10) of the controls manifested
      hydronephrosis. MSG-treated rats had significantly higher levels of serum
      creatinine and potassium including urine output volume, urinary excretion sodium
      and citrate compared to controls. In contrast, MSG-treated rats had significantly
      lower ammonium and magnesium urinary excretion. CONCLUSION: Oral MSG consumption
      appears to cause alkaline urine and may increase the risks of kidney stones with
      hydronephrosis in rats. Similar effects in humans must be verified by dedicated
      studies.

PMID- 24086563
TI  - Proximal tubular hypertrophy and enlarged glomerular and proximal tubular urinary
      space in obese subjects with proteinuria.
AB  - BACKGROUND: Obesity is associated with glomerular hyperfiltration, increased
      proximal tubular sodium reabsorption, glomerular enlargement and renal
      hypertrophy. A single experimental study reported an increased glomerular urinary
      space in obese dogs. Whether proximal tubular volume is increased in obese
      subjects and whether their glomerular and tubular urinary spaces are enlarged is
      unknown. OBJECTIVE: To determine whether proximal tubules and glomerular and
      tubular urinary space are enlarged in obese subjects with proteinuria and
      glomerular hyperfiltration. METHODS: Kidney biopsies from 11 non-diabetic obese
      with proteinuria and 14 non-diabetic lean patients with a creatinine clearance
      above 50 ml/min and with mild or no interstitial fibrosis were retrospectively
      analyzed using morphometric methods. The cross-sectional area of the proximal
      tubular epithelium and lumen, the volume of the glomerular tuft and of Bowman's
      space and the nuclei number per tubular profile were estimated. RESULTS:
      Creatinine clearance was higher in the obese than in the lean group (P=0.03).
      Proteinuria was similarly increased in both groups. Compared to the lean group,
      the obese group displayed a 104% higher glomerular tuft volume (P=0.001), a 94%
      higher Bowman's space volume (P=0.003), a 33% higher cross-sectional area of the
      proximal tubular epithelium (P=0.02) and a 54% higher cross-sectional area of the
      proximal tubular lumen (P=0.01). The nuclei number per proximal tubular profile
      was similar in both groups, suggesting that the increase in tubular volume is due
      to hypertrophy and not to hyperplasia. CONCLUSIONS: Obesity-related glomerular
      hyperfiltration is associated with proximal tubular epithelial hypertrophy and
      increased glomerular and tubular urinary space volume in subjects with
      proteinuria. The expanded glomerular and urinary space is probably a direct
      consequence of glomerular hyperfiltration. These effects may be involved in the
      pathogenesis of obesity-related renal disease.

PMID- 24086564
TI  - Differentiation of mouse induced pluripotent stem cells (iPSCs) into nucleus
      pulposus-like cells in vitro.
AB  - A large percentage of the population may be expected to experience painful
      symptoms or disability associated with intervertebral disc (IVD) degeneration - a
      condition characterized by diminished integrity of tissue components. Great
      interest exists in the use of autologous or allogeneic cells delivered to the
      degenerated IVD to promote matrix regeneration. Induced pluripotent stem cells
      (iPSCs), derived from a patient's own somatic cells, have demonstrated their
      capacity to differentiate into various cell types although their potential to
      differentiate into an IVD cell has not yet been demonstrated. The overall
      objective of this study was to assess the possibility of generating iPSC-derived
      nucleus pulposus (NP) cells in a mouse model, a cell population that is entirely
      derived from notochord. This study employed magnetic activated cell sorting
      (MACS) to isolate a CD24(+) iPSC subpopulation. Notochordal cell-related gene
      expression was analyzed in this CD24(+) cell fraction via real time RT-PCR.
      CD24(+) iPSCs were then cultured in a laminin-rich culture system for up to 28
      days, and the mouse NP phenotype was assessed by immunostaining. This study also
      focused on producing a more conducive environment for NP differentiation of mouse
      iPSCs with addition of low oxygen tension and notochordal cell conditioned medium
      (NCCM) to the culture platform. iPSCs were evaluated for an ability to adopt an
      NP-like phenotype through a combination of immunostaining and biochemical assays.
      Results demonstrated that a CD24(+) fraction of mouse iPSCs could be retrieved
      and differentiated into a population that could synthesize matrix components
      similar to that in native NP. Likewise, the addition of a hypoxic environment and
      NCCM induced a similar phenotypic result. In conclusion, this study suggests that
      mouse iPSCs have the potential to differentiate into NP-like cells and suggests
      the possibility that they may be used as a novel cell source for cellular therapy
      in the IVD. 

PMID- 24086565
TI  - A DNA element regulates drug tolerance and withdrawal in Drosophila.
AB  - Drug tolerance and withdrawal are insidious responses to drugs of abuse; the
      first increases drug consumption while the second punishes abstention. Drosophila
      generate functional tolerance to benzyl alcohol sedation by increasing neural
      expression of the slo BK-type Ca(2+) activated K(+) channel gene. After drug
      clearance this change produces a withdrawal phenotype-increased seizure
      susceptibility. The drug-induced histone modification profile identified the 6b
      element (60 nt) as a drug responsive element. Genomic deletion of 6b produces the
      allele, slo (Delta6b), that reacts more strongly to the drug with increased
      induction, a massive increase in the duration of tolerance, and an increase in
      the withdrawal phenotype yet does not alter other slo-dependent behaviors. The 6b
      element is a homeostatic regulator of BK channel gene expression and is the first
      cis-acting DNA element shown to specifically affect the duration of a drug
      action. 

PMID- 24086566
TI  - Leptin induces IL-6 expression through OBRl receptor signaling pathway in human
      synovial fibroblasts.
AB  - BACKGROUND: Leptin, an adipocyte-secreted hormone that centrally regulates weight
      control, may exert proinflammatory effects in the joint, depending on the immune
      response. Leptin is abundantly expressed in osteoarthritis (OA) cartilage and
      synovium. However, the relationship between leptin and interleukin-6 (IL-6) in OA
      synovial fibroblasts (OASFs) remains obscure. METHODOLOGY/PRINCIPAL FINDINGS:
      Stimulation of OASFs with leptin induced IL-6 expression in a concentration- and
      time-dependent manner. OASFs expressed the long (OBRl) and short (OBRs) isoforms
      of the leptin receptor. However, OBRl, but not OBRs, antisense oligonucleotide
      (AS-ODN) abolished the leptin-mediated increase of IL-6 expression. Transfection
      with insulin receptor substrate (IRS)-1 siRNA decreased leptin-induced IL-6
      production. In addition, pretreatment of cells with PI3K, Akt, or AP-1 inhibitor
      also inhibited the potentiating action of leptin. Leptin-induced AP-1 activation
      was inhibited by OBRl, IRS-1, PI3K, or Akt inhibitors and siRNAs.
      CONCLUSIONS/SIGNIFICANCE: Our results showed that leptin activates the OBRl
      receptor, which in turn activates IRS-1, PI3K, Akt, and AP-1 pathway, leading to
      up-regulation of IL-6 expression.

PMID- 24086567
TI  - Vaccinating women previously exposed to human papillomavirus: a cost
      effectiveness analysis of the bivalent vaccine.
AB  - Recent trials have indicated that women with prior exposure to Human
      papillomavirus (HPV) subtypes 16/18 receive protection against reinfection from
      the HPV vaccines. However, many of the original models investigating the cost
      effectiveness of different vaccination strategies for the protection of cervical
      cancer assumed, based on the trial results at that time, that these women
      received no protection. We developed a deterministic, dynamic transmission model
      that incorporates the vaccine-induced protection of women with prior exposure to
      HPV. The model was used to estimate the cost effectiveness of progressively
      extending a vaccination programme using the bivalent vaccine to older age groups
      both with and without protection of women with prior exposure. We did this under
      a range of assumptions on the level of natural immunity. Our modelling
      projections indicate that including the protection of women with prior HPV
      exposure can have a profound effect on the cost effectiveness of vaccinating
      adults. The impact of this protection is inversely related to the level of
      natural immunity. Our results indicate that adult vaccination strategies should
      potentially be reassessed, and that it is important to include the protection of
      non-naive women previously infected with HPV in future studies. Furthermore, they
      also highlight the need for a more thorough investigation of this protection. 

PMID- 24086568
TI  - Molecular analysis of endocrine disruption in hornyhead turbot at wastewater
      outfalls in southern california using a second generation multi-species
      microarray.
AB  - Sentinel fish hornyhead turbot (Pleuronichthysverticalis) captured near
      wastewater outfalls are used for monitoring exposure to industrial and
      agricultural chemicals of ~ 20 million people living in coastal Southern
      California. Although analyses of hormones in blood and organ morphology and
      histology are useful for assessing contaminant exposure, there is a need for
      quantitative and sensitive molecular measurements, since contaminants of emerging
      concern are known to produce subtle effects. We developed a second generation
      multi-species microarray with expanded content and sensitivity to investigate
      endocrine disruption in turbot captured near wastewater outfalls in San Diego,
      Orange County and Los Angeles California. Analysis of expression of genes
      involved in hormone [e.g., estrogen, androgen, thyroid] responses and xenobiotic
      metabolism in turbot livers was correlated with a series of phenotypic end
      points. Molecular analyses of turbot livers uncovered altered expression of
      vitellogenin and zona pellucida protein, indicating exposure to one or more
      estrogenic chemicals, as well as, alterations in cytochrome P450 (CYP) 1A, CYP3A
      and glutathione S-transferase-alpha indicating induction of the detoxification
      response. Molecular responses indicative of exposure to endocrine disruptors were
      observed in field-caught hornyhead turbot captured in Southern California
      demonstrating the utility of molecular methods for monitoring environmental
      chemicals in wastewater outfalls. Moreover, this approach can be adapted to
      monitor other sites for contaminants of emerging concern in other fish species
      for which there are few available gene sequences. 

PMID- 24086569
TI  - Smad3 inactivation and MiR-29b upregulation mediate the effect of carvedilol on
      attenuating the acute myocardium infarction-induced myocardial fibrosis in rat.
AB  - Carvedilol, a nonselective beta-adrenoreceptor antagonist, protects against
      myocardial injury induced by acute myocardium infarction (AMI). The mechanisms
      underlying the anti-fibrotic effects of carvedilol are unknown. Recent studies
      have revealed the critical role of microRNAs (miRNAs) in a variety of
      cardiovascular diseases. This study investigated whether miR-29b is involved in
      the cardioprotective effect of carvedilol against AMI-induced myocardial
      fibrosis. Male SD rats were randomized into several groups: the sham surgery
      control, left anterior descending (LAD) surgery-AMI model, AMI plus low-dose
      carvedilol treatment (1 mg/kg per day, CAR-L), AMI plus medium-dose carvedilol
      treatment (5 mg/kg per day, CAR-M) and AMI plus high-dose carvedilol treatment
      (10 mg/kg per day, CAR-H). Cardiac remodeling and impaired heart function were
      observed 4 weeks after LAD surgery treatment; the observed cardiac remodeling,
      decreased ejection fraction, and fractional shortening were rescued in the CAR-M
      and CAR-H groups. The upregulated expression of Col1a1, Col3a1, and alpha-SMA
      mRNA was significantly reduced in the CAR-M and CAR-H groups. Moreover, the
      downregulated miR-29b was elevated in the CAR-M and CAR-H groups. The in vitro
      study showed that Col1a1, Col3a1, and alpha-SMA were downregulated and miR-29b
      was upregulated by carvedilol in a dose-dependent manner in rat cardiac
      fibroblasts. Inhibition of ROS-induced Smad3 activation by carvedilol resulted in
      downregulation of Col1a1, Col3a1, and alpha-SMA and upregulation of miR-29b
      derived from the miR-29b-2 precursor. Enforced expression of miR-29b
      significantly suppressed Col1a1, Col3a1, and alpha-SMA expression. Taken
      together, we found that smad3 inactivation and miR-29b upregulation contributed
      to the cardioprotective activity of carvedilol against AMI-induced myocardial
      fibrosis. 

PMID- 24086570
TI  - Comparison of the prevalence of common bacterial pathogens in the oropharynx and
      nasopharynx of gambian infants.
AB  - BACKGROUND: CRM- based pneumococcal conjugate vaccines generally have little
      impact on the overall prevalence of pneumococcal carriage because of serotype
      replacement. In contrast, protein vaccines could substantially reduce the overall
      prevalence of pneumococcal carriage with potential microbiological and clinical
      consequences. Therefore, trials of pneumococcal protein vaccines need to evaluate
      their impact on carriage of other potentially pathogenic bacteria in addition to
      the pneumococcus. METHODS: As a prelude to a trial of an investigational
      pneumococcal vaccine containing pneumococcal polysaccharide conjugates and
      pneumococcal proteins, the prevalence of carriage of Streptococcus pneumoniae,
      Haemophilus influenzae, Moraxella species and Staphylococcus aureus in the
      nasopharynx of 1030 Gambian infants (median age 35 weeks) was determined. An
      oropharyngeal swab was obtained at the same time from the first 371 infants
      enrolled. Standard microbiological techniques were used to evaluate the bacterial
      flora of the pharynx and to compare that found in the oropharynx and in the
      nasopharynx. RESULTS: The overall pneumococcal carriage rate was high. Isolation
      rates of S. pneumoniae and Moraxella species were significantly higher using
      nasopharyngeal rather than oropharyngeal swabs (76.1% [95% CI 73.4%,78.7%] vs.
      21.3% [95% CI 17.2%,25.8%] and 48.9% [95% CI 45.8%, 52.0%] vs. 20.5% % [95% CI
      16.5%,25.0%] respectively). In contrast, S. aureus and H. influenzae were
      isolated more frequently from oropharyngeal than from nasopharyngeal swabs (65.0%
      [95% CI 59.9%, 69.8%] vs. 33.6% [95% CI 30.7%, 36.5%] and 31.8% [95% CI 16.5%,
      25.0%] vs. 22.4% [95% CI 19.9%, 25.1%] respectively). No group A beta haemolytic
      streptococci were isolated. CONCLUSION: Collection of an oropharyngeal swab in
      addition to a nasopharyngeal swab will provide little additional information on
      the impact of a novel pneumococcal vaccine on pneumococcal carriage but it might
      provide additional, valuable information on the impact of the vaccine on the
      overall microbiota of the pharynx.

PMID- 24086571
TI  - Association between Helicobacter pylori infection and pancreatic cancer
      development: a meta-analysis.
AB  - BACKGROUND: Pancreatic cancer is one of the most troublesome malignancies with
      dismal prognosis. H. pylori has been recognized as a type I carcinogen. Several
      studies have evaluated the association between H. pylori infection and pancreatic
      cancer development, however, the conclusions are inconsistent. METHODS:
      Literature search was carried out in PubMed, EMBASE, Cochrane Library and CNKI
      databases to identify eligible researches. We performed overall meta-analysis of
      all studies included and subgroup analysis based on regional distribution.
      Quality of the studies (assessed by Newcastle-Ottawa quality assessment scale for
      case-control studies) and CagA+ strains of H. pylori were taken into
      consideration, and we conducted additional analyses including high-quality
      researches and those concerning CagA+ H. pylori respectively. RESULTS: 9 studies
      involving 3033 subjects (1083 pancreatic cancer cases, 1950 controls) were
      included. Summary OR and 95%CI of the overall meta-analysis of all included
      studies were 1.47 and 1.22-1.77, pooled data of the 4 high-quality studies were
      OR 1.28, 95%CI 1.01-1.63. OR of the 5 studies examined CagA+ strains was 1.42,
      corresponding 95%CI was 0.79 to 2.57. Summary estimates of subgroup analysis
      based on regional distribution are as follows, Europe group: OR 1.56, 95%CI 1.15
      2.10; East Asia group: OR 2.01, 95%CI 1.33-3.02; North America group: OR 1.17,
      95%CI 0.87-1.58. There was not obvious heterogeneity across the 9 studies. No
      publication bias was detected. CONCLUSION: H. pylori infection is significantly,
      albeit weakly, associated with pancreatic cancer development. The association is
      prominent in Europe and East Asia, but not in North America. CagA+ H. pylori
      strains appear not to be associated with pancreatic cancer. However, more
      studies, especially prospective studies, are needed to validate our results.

PMID- 24086572
TI  - Surgery-related thrombosis critically affects the brain infarct volume in mice
      following transient middle cerebral artery occlusion.
AB  - Transient middle cerebral artery occlusion (tMCAO) model is widely used to mimic
      human focal ischemic stroke in order to study ischemia/reperfusion brain injury
      in rodents. In tMCAO model, intraluminal suture technique is widely used to
      achieve ischemia and reperfusion. However, variation of infarct volume in this
      model often requires large sample size, which hinders the progress of preclinical
      research. Our previous study demonstrated that infarct volume was related to the
      success of reperfusion although the reason remained unclear. The aim of present
      study is to explore the relationship between focal thrombus formation and model
      reproducibility with respect to infarct volume. We hypothesize that suture
      induced thrombosis causes infarct volume variability due to insufficient
      reperfusion after suture withdrawal. Seventy-two adult male CD-1 mice underwent
      90 minutes of tMCAO with or without intraperitoneal administration of heparin.
      Dynamic synchrotron radiation microangiography (SRA) and laser speckle contrast
      imaging (LSCI) were performed before and after tMCAO to observe the cerebral
      vascular morphology and to measure the cerebral blood flow in vivo. Infarct
      volume and neurological score were examined to evaluate severity of ischemic
      brain injury. We found that the rate of successful reperfusion was much higher in
      heparin-treated mice compared to that in heparin-free mice according to the
      result of SRA and LSCI at 1 and 3 hours after suture withdrawal (p<0.05).
      Pathological features and SRA revealed that thrombus formed in the internal
      carotid artery, middle cerebral artery or anterior cerebral artery, which blocked
      reperfusion following tMCAO. LSCI showed that cortical collateral circulation
      could be disturbed by thrombi. Our results demonstrated that suture-induced
      thrombosis was a critical element, which affects the success of reperfusion.
      Appropriate heparin management provides a useful approach for improving
      reproducibility of reperfusion model in mice. 

PMID- 24086573
TI  - A low-molecular-weight compound K7174 represses hepcidin: possible therapeutic
      strategy against anemia of chronic disease.
AB  - Hepcidin is the principal iron regulatory hormone, controlling the systemic
      absorption and remobilization of iron from intracellular stores. The expression
      of the hepcidin gene, HAMP, is increased in patients with anemia of chronic
      disease. Previously, the synthetic compound K7174 was identified through chemical
      screening as a novel inhibitor of the adhesion of monocytes to cytokine
      stimulated endothelial cells. K7174 also ameliorated anemia induced by
      inflammatory cytokines in mice, which suggests a possible involvement of hepcidin
      regulation. The present study was performed to assess the impact of K7174 on
      hepcidin expression in a human hematoma cell line and in mice in vivo. We first
      demonstrated that K7174 treatment in HepG2 cells significantly decreased HAMP
      expression. Then, we conducted microarray analysis to determine the molecular
      mechanism by which K7174 inhibits HAMP expression. Transcriptional profiling
      confirmed the downregulation of HAMP. Surprisingly, we found that K7174 strongly
      induced GDF15, known as a negative regulator of HAMP expression. Western blotting
      analysis as well as ELISA confirmed the induction of GDF15 by K7174 treatment.
      Furthermore, K7174-mediated HAMP suppression was rescued by the silencing of
      GDF15 expression. Interestingly, we found that K7174 also upregulates CEBPB.
      Promoter analysis and chromatin immunoprecipitation analysis revealed that CEBPB
      could contribute to K7174-mediated transcriptional activation of GDF15.
      Subsequently, we also examined whether K7174 inhibits hepcidin expression in
      mice. Quantitative RT-PCR analysis with liver samples from K7174-treated mice
      demonstrated significant upregulation of Gdf15 and downregulation of Hamp
      expression, as compared to control mice. Furthermore, serum hepcidin
      concentration was also significantly decreased in K7174-treated mice. In
      conclusion, K7174 inhibits hepcidin expression partly by inducing GDF15. K-7174
      may be a potential therapeutic option to treat anemia of chronic disease. 

PMID- 24086574
TI  - Smad2-dependent downregulation of miR-30 is required for TGF-beta-induced
      apoptosis in podocytes.
AB  - Transforming growth factors beta (TGF-beta) are multi-functional cytokines
      capable of inducing apoptosis in epithelial cells, including glomerular
      podocytes. We and others have previously shown that podocyte-selective genetic
      deletion of the microRNA (miR)-processing enzyme, Dicer, caused
      glomerulosclerosis that was associated with podocyte apoptosis, and the miR-30
      family was implicated in the process. Here, we report that apoptosis-associated
      genes were highly enriched among the predicted targets of miR-30 when compared
      with randomly selected miRs (26% vs. 4.5 +/- 2.1%) or with the known TGF-beta
      regulated miR-192 (6%), miR-216a (5.1%), and miR-217 (0%). miR-30 family members
      were abundantly expressed in podocytes in normal mice but were downregulated in
      albumin/TGF-beta transgenic mice with podocyte apoptosis and glomerulosclerosis.
      In vitro, TGF-beta downregulated miR-30s in wildtype and Smad3-deficient, but not
      Smad2- or Smad2/Smad3-deficient, podocytes. The TGF-beta-induced activation of
      caspase 3 and an increase in TUNEL-positive nuclei were significantly inhibited
      by the lentivirus-mediated overexpression of miR-30d, but not by a scrambled
      control miR, in podocytes. TGF-beta stimulated the phosphorylation of pro
      apoptotic p53 in podocytes with lentiviral expression of a scrambled miR, but not
      in podocytes expressing miR-30d. In contrast, miR-30d had no effect on the
      phosphorylation of pro-apoptotic p38 MAP kinase induced by TGF-beta. Thus, we
      report that Smad2-dependent inhibition of miR-30s in podocytes is required for
      the activation of p53 and the induction of apoptosis by TGF-beta. These results
      demonstrate a novel functional role for miR-30 in podocyte survival and indicate
      that the loss of miR-30 survival signaling is a novel and specific mechanism of
      TGF-beta-induced podocyte apoptosis during glomerulosclerosis. We propose the
      therapeutic replacement of miR-30 as a novel strategy to prevent the podocyte
      apoptosis that is characteristic of progressive glomerular diseases. 

PMID- 24086575
TI  - Adult attention deficit hyperactivity disorder and violence in the population of
      England: does comorbidity matter?
AB  - BACKGROUND: It is unclear whether the association between Attention
      Deficit/Hyperactivity Disorder (ADHD) and violence is explained by ADHD symptoms
      or co-existing psychopathology. We investigated associations of ADHD and its
      symptom domains of hyperactivity and inattention, among individuals reporting
      violence in the UK population. METHODS: We report data from the Adult Psychiatric
      Morbidity Survey (2007), a representative sample of the household population of
      England. A randomly selected sample of 7,369 completed the Adult Self-Report
      Scale for ADHD and the self-reported violence module, including repetition,
      injury, minor violence, victims and location of incidents. All models were
      weighted to account for non-response and carefully adjusted for demography and
      clinical predictors of violence: antisocial personality, substance misuse and
      anxiety disorders. RESULTS: ADHD was moderately associated with violence after
      adjustments (OR 1.75, p = .01). Hyperactivity, but not inattention was associated
      with several indicators of violence in the domestic context (OR 1.16, p = .03).
      Mild and moderate ADHD symptoms were significantly associated with violence
      repetition, but not severe ADHD where the association was explained by co
      existing disorders. Stratified analyses further indicated that most violence
      reports are associated with co-occurring psychopathology. CONCLUSIONS: The direct
      effect of ADHD on violence is only moderate at the population level, driven by
      hyperactivity, and involving intimate partners and close persons. Because
      violence associated with severe ADHD is explained by co-existing psychopathology,
      interventions should primarily target co-existing disorders.

PMID- 24086576
TI  - Filopodia and membrane blebs drive efficient matrix invasion of macrophages
      transformed by the intracellular parasite Theileria annulata.
AB  - Recent technical advances have broadened our understanding of processes that
      govern mammalian cell migration in health and disease but many of the molecular
      and morphological alterations that precede and accompany movement of cells - in
      particular in three-dimensional (3D) environments - are still incompletely
      understood. In this manuscript, using high-resolution and time-lapse microscopy
      imaging approaches, we describe morphodynamic processes during rounded/amoeboid
      cell invasion and molecules associated with the cellular invasion structures. We
      used macrophages infected with the intracellular protozoan parasite Theileria
      annulata, which causes Tropical Theileriosis in susceptible ruminants such as
      domestic cattle. T. annulata transforms its host cell that, as a result, acquires
      many characteristics of human cancer cells including a markedly increased
      potential to migrate, disseminate and expand in the body of the host animal.
      Hence, virulence of the disease is associated with the capability of infected
      cells to disseminate inside the host. Using T. annulata-transformed macrophages
      as a model system, we described a novel mode of rounded/amoeboid macrophage
      migration. We show that filopodia-like membrane extensions at the leading edge
      lead the way and further evolve in blebbing membrane protrusions to promote
      progressive expansion of the matrix. Associated with focal invasion structures we
      detected ezrin, radixin, moesin-family proteins and their regulatory kinase
      MAP4K4. Furthermore, we linked Rho-kinase activity to contractile force
      generation, which is essential for infected cell motility. Thus, the motility
      mode of these parasite-transformed macrophages contrasts with those described so
      far in human macrophages such as the tunneling or mesenchymal modes, which
      require engulfment, compaction and ingestion of matrix or proteolytic matrix
      degradation, respectively. Together, our data reveal protrusion dynamics at the
      leading edge of invading cells in 3D at unprecedented temporal and spatial
      resolution and suggest a novel mode of rounded/amoeboid invasive cell motility
      that exploits actin-driven filopodia formation in combination with pressure
      driven membrane blebs. 

PMID- 24086577
TI  - Regulation of PTEN/Akt pathway enhances cardiomyogenesis and attenuates adverse
      left ventricular remodeling following thymosin beta4 Overexpressing embryonic
      stem cell transplantation in the infarcted heart.
AB  - Thymosin beta4 (Tbeta4), a small G-actin sequestering peptide, mediates cell
      proliferation, migration, and angiogenesis. Whether embryonic stem (ES) cells,
      overexpressing Tbeta4, readily differentiate into cardiac myocytes in vitro and
      in vivo and enhance cardioprotection following transplantation post myocardial
      infarction (MI) remains unknown. Accordingly, we established stable mouse ES cell
      lines, RFP-ESCs and Tbeta4-ESCs, expressing RFP and an RFP-Tbeta4 fusion protein,
      respectively. In vitro, the number of spontaneously beating embryoid bodies (EBs)
      was significantly increased in Tbeta4-ESCs at day 9, 12 and 15, compared with RFP
      ESCs. Enhanced expression of cardiac transcriptional factors GATA-4, Mef2c and
      Txb6 in Tbeta4-EBs, as confirmed with real time-PCR analysis, was accompanied by
      the increased number of EB areas stained positive for sarcomeric alpha-actin in
      Tbeta4-EBs, compared with the RFP control, suggesting a significant increase in
      functional cardiac myocytes. Furthermore, we transplanted Tbeta4-ESCs into the
      infarcted mouse heart and performed morphological and functional analysis 2 weeks
      after MI. There was a significant increase in newly formed cardiac myocytes
      associated with the Notch pathway, a decrease in apoptotic nuclei mediated by an
      increase in Akt and a decrease in levels of PTEN. Cardiac fibrosis was
      significantly reduced, and left ventricular function was significantly augmented
      in the Tbeta4-ESC transplanted group, compared with controls. It is concluded
      that genetically modified Tbeta4-ESCs, potentiates their ability to turn into
      cardiac myocytes in vitro as well as in vivo. Moreover, we also demonstrate that
      there was a significant decrease in both cardiac apoptosis and fibrosis, thus
      improving cardiac function in the infarcted heart. 

PMID- 24086578
TI  - Putative bioactive motif of tritrpticin revealed by an antibody with biological
      receptor-like properties.
AB  - Antimicrobial peptides represent one of the most promising future strategies for
      combating infections and microbial drug resistance. Tritrpticin is a 13mer
      tryptophan-rich cationic antimicrobial peptide with a broad spectrum of activity
      whose application in antimicrobial therapy has been hampered by ambiguity about
      its biological target and consequently the molecular interactions necessary for
      its antimicrobial activity. The present study provides clues about the mechanism
      of action of tritripticin by using a unique monoclonal antibody (mAb) as a
      'physiological' structural scaffold. A pool of mAbs were generated against
      tritrpticin and based on its high affinity and ability to bind tritrpticin
      analogs, mAb 6C6D7 was selected and characterized further. In a screening of
      phage displayed random peptides, this antibody was able to identify a novel
      antimicrobial peptide with low sequence homology to tritrpticin, suggesting that
      the mAb possessed the physico-chemical characteristics mimicking the natural
      receptor. Subsequently, thermodynamics and molecular modeling identified a core
      group of hydrophobic residues in tritrpticin arranged in a distorted's' shaped
      conformation as critical for antibody binding. Comparison of the mAb induced
      conformation with the micelle bound structure of tritrpticin reveals how a common
      motif may be able to interact with multiple classes of biomolecules thus
      extending the target range of this innate immune peptide. Based on the
      concurrence between thermodynamic and structural data our results reveal a
      template that can be used to design novel antimicrobial pharmacophores while
      simultaneously demonstrating at a more fundamental level the potential of mAbs to
      act as receptor surrogates. 

PMID- 24086579
TI  - Clinical impact of hospital-acquired anemia in association with acute kidney
      injury and chronic kidney disease in patients with acute myocardial infarction.
AB  - BACKGROUND: Hospital-acquired anemia (HAA) is common in patients with acute
      myocardial infarction (AMI) and is an independent indicator of long-term
      mortality in these patients. However, limited information exists regarding the
      development and prognostic impact of HAA associated with acute kidney injury
      (AKI) and chronic kidney disease (CKD) in AMI patients. METHODS AND RESULTS: We
      retrospectively analyzed 2,289 patients with AMI, and excluded those with anemia
      at admission. The study population included 1,368 patients, of whom 800 (58.5%)
      developed HAA. Age, Hgb level at admission, Length of hospital stay, documented
      in-hospital bleeding and use of glycoprotein IIb/IIIa inhibitor, presence of CKD
      and occurrence of AKI were significantly associated with the development of HAA.
      HAA was significantly associated with higher 3-year mortality (4.8% and 11.4% for
      non-HAA and HAA patients, respectively; P < 0.001). After adjustment for
      multivariable confounders, the risk for long-term mortality was increased in HAA
      patients with AKI and/or CKD but not in HAA patients without AKI and/or CKD,
      compared to non-HAA patients (HAA patients without AKI and CKD, hazard ratio
      [HR]: 1.34, 95% confidence interval [CI]: 0.70-2.56; HAA patients with either AKI
      or CKD, HR: 2.80, 95% CI: 1.37-5.73; HAA patients with AKI and CKD, HR: 3.25, 95%
      CI: 1.28-8.24; compared with the non-HAA group). CONCLUSION: AKI and CKD were
      strongly associated with the development of HAA in AMI patients. HAA, when
      accompanied by AKI or CKD, is an independent risk predictor for long-term
      mortality in AMI patients.

PMID- 24086580
TI  - Retargeting T cells for HER2-positive tumor killing by a bispecific Fv-Fc
      antibody.
AB  - To exploit the biological and pharmacological properties of immunoglobulin
      constant domain Fc fragment and increase the killing efficacy of T cells, a
      single chain variable fragment specific to CD3 was fused with Fcab (Fc antigen
      binding), a mutant Fc fragment with specificity against Human epidermal growth
      factor receptor 2 (HER2) developed by F-star. The bispecific fusion named as
      FcabCD3 was expressed by transient transfection in HEK-293T cells and purified by
      affinity chromatography. Specific cytolytic activity of retargeted T cells to
      kill HER2 positive SKBR3 cell line was evaluated in vitro. FcabCD3 was able to
      retarget T cells to kill both Herceptin insensitive Colo205-luc cell line and
      HER2 low expression MDA-MB-231-luc cell line. Furthermore, FcabCD3 was effective
      in eliminating the Colo205 tumor established on BALB/c nu/nu mice. 

PMID- 24086581
TI  - Randomized controlled trial of parent therapeutic education on antibiotics to
      improve parent satisfaction and attitudes in a pediatric emergency department.
AB  - OBJECTIVE: To evaluate therapeutic education delivered in a pediatric emergency
      department to improve parents' satisfaction and attitudes about judicious
      antibiotic use. METHODS: In an emergency department of a tertiary pediatric
      hospital, children aged 1 month to 6 years and discharged with an oral antibiotic
      prescription for an acute respiratory or urinary tract infection were randomized
      to a patient therapeutic education on antibiotic use (intervention group) or
      fever control (control group) delivered to the parents (in the presence of the
      children) by a pharmacist trained in therapeutic education. Education consisted
      in a 30-minute face-to-face session with four components: educational diagnosis,
      educational contract, education, and evaluation. The main outcome measure was
      parent satisfaction about information on antibiotics received at the hospital, as
      assessed by a telephone interview on day 14. The secondary outcome was attitudes
      about antibiotic use evaluated on day 14 and at month 6. RESULTS: Of the 300
      randomized children, 150 per arm, 259 were evaluated on day 14. Parent
      satisfaction with information on antibiotics was higher in the intervention group
      (125/129, 96.9%, versus 108/130, 83.0%; P=0.002, exact Fisher test).
      INTERVENTION: Group parents had higher proportions of correct answers on day 14
      to questions on attitudes about judicious antibiotic use than did control-group
      parents (P=0.017, Mann-Whitney U test). CONCLUSION: Therapeutic education
      delivered by a clinical pharmacist in the pediatric emergency department holds
      promise for improving the use of antibiotics prescribed to pediatric outpatients.
      TRIAL REGISTRATION: ClinicalTrials.gov NCT00948779
      http://clinicaltrials.gov/show/NCT00948779.

PMID- 24086582
TI  - Neonatal mucosal immune stimulation by microbial superantigen improves the
      tolerogenic capacity of CD103(+) dendritic cells.
AB  - Food allergy represents failure to develop tolerance to dietary proteins. Food
      allergy has increased in prevalence in parallel with decreased exposure to
      microbes during infancy. In mice, neonatal peroral exposure to the strongly T
      cell stimulating superantigen staphylococcal enterotoxin A (SEA), enhances the
      capacity to develop oral tolerance to a novel antigen encountered in adult life.
      A population of antigen-presenting cells in the gut, the CD103(+) dendritic cells
      (DCs), is thought to be involved in oral tolerance development, as they convert
      naive T cells into FoxP3(+) regulatory T cells (Treg). This function depends on
      their capacity to convert vitamin A to retinoic acid, carried out by the retinal
      aldehyde dehydrogenase (RALDH) enzyme. Here, newborn mice were treated with
      superantigen and DC function and tolerogenic capacity was examined at six weeks
      of age. We observed that, in mice fed superantigen neonatally, the CD11c(+) DCs
      had increased expression of RALDH and in vitro more efficiently induced
      expression Foxp3 expression to stimulated T cells. Further, these mice showed an
      accumulation of FoxP3(+) T cells in the small intestinal lamina propria and had a
      more Ag-specific FoxP3(+) T cells after oral tolerance induction in vivo.
      Moreover, the improved oral tolerance, as shown by increased protection from food
      allergy, was eradicated if the Vitamin A metabolism was inhibited. These
      observations contribute to the understanding of how a strong immune stimulation
      during the neonatal period influences the maturation of the immune system and
      suggests that such stimulation may reduce the risk of later allergy development. 

PMID- 24086583
TI  - Use of MSAP markers to analyse the effects of salt stress on DNA methylation in
      rapeseed (Brassica napus var. oleifera).
AB  - Excessive soil salinity is a major ecological and agronomical problem, the
      adverse effects of which are becoming a serious issue in regions where saline
      water is used for irrigation. Plants can employ regulatory strategies, such as
      DNA methylation, to enable relatively rapid adaptation to new conditions. In this
      regard, cytosine methylation might play an integral role in the regulation of
      gene expression at both the transcriptional and post-transcriptional levels.
      Rapeseed, which is the most important oilseed crop in Europe, is classified as
      being tolerant of salinity, although cultivars can vary substantially in their
      levels of tolerance. In this study, the Methylation Sensitive Amplified
      Polymorphism (MSAP) approach was used to assess the extent of cytosine
      methylation under salinity stress in salinity-tolerant (Exagone) and salinity
      sensitive (Toccata) rapeseed cultivars. Our data show that salinity affected the
      level of DNA methylation. In particular methylation decreased in Exagone and
      increased in Toccata. Nineteen DNA fragments showing polymorphisms related to
      differences in methylation were sequenced. In particular, two of these were
      highly similar to genes involved in stress responses (Lacerata and trehalose-6
      phosphatase synthase S4) and were chosen to further characterization. Bisulfite
      sequencing and quantitative RT-PCR analysis of selected MSAP loci showed that
      cytosine methylation changes under salinity as well as gene expression varied. In
      particular, our data show that salinity stress influences the expression of the
      two stress-related genes. Moreover, we quantified the level of trehalose in
      Exagone shoots and found that it was correlated to TPS4 expression and,
      therefore, to DNA methylation. In conclusion, we found that salinity could induce
      genome-wide changes in DNA methylation status, and that these changes, when
      averaged across different genotypes and developmental stages, accounted for 16.8%
      of the total site-specific methylation differences in the rapeseed genome, as
      detected by MSAP analysis. 

PMID- 24086584
TI  - The effect of emotional content on brain activation and the late positive
      potential in a word n-back task.
AB  - INTRODUCTION: There is mounting evidence for the influence of emotional content
      on working memory performance. This is particularly important in light of the
      emotion processing that needs to take place when emotional content interferes
      with executive functions. In this study, we used emotional words of different
      valence but with similar arousal levels in an n-back task. METHODS: We examined
      the effects on activation in the prefrontal cortex by means of functional near
      infrared spectroscopy (fNIRS) and on the late positive potential (LPP). FNIRS and
      LPP data were examined in 30 healthy subjects. RESULTS: BEHAVIORAL RESULTS SHOW
      AN INFLUENCE OF VALENCE ON THE ERROR RATE DEPENDING ON THE DIFFICULTY OF THE
      TASK: more errors were made when the valence was negative and the task difficult.
      Brain activation was dependent both on the difficulty of the task and on the
      valence: negative valence of a word diminished the increase in activation,
      whereas positive valence did not influence the increase in activation, while
      difficulty levels increased. The LPP also differentiated between the different
      valences, and in addition was influenced by the task difficulty, the more
      difficult the task, the less differentiation could be observed. CONCLUSIONS:
      Summarized, this study shows the influence of valence on a verbal working memory
      task. When a word contained a negative valence, the emotional content seemed to
      take precedence in contrast to words containing a positive valence. Working
      memory and emotion processing sites seemed to overlap and compete for resources
      even when words are carriers of the emotional content.

PMID- 24086585
TI  - New pyrazolopyrimidine inhibitors of protein kinase d as potent anticancer agents
      for prostate cancer cells.
AB  - The emergence of protein kinase D (PKD) as a potential therapeutic target for
      several diseases including cancer has triggered the search for potent, selective,
      and cell-permeable small molecule inhibitors. In this study, we describe the
      identification, in vitro characterization, structure-activity analysis, and
      biological evaluation of a novel PKD inhibitory scaffold exemplified by 1
      naphthyl PP1 (1-NA-PP1). 1-NA-PP1 and IKK-16 were identified as pan-PKD
      inhibitors in a small-scale targeted kinase inhibitor library assay. Both
      screening hits inhibited PKD isoforms at about 100 nM and were ATP-competitive
      inhibitors. Analysis of several related kinases indicated that 1-NA-PP1 was
      highly selective for PKD as compared to IKK-16. SAR analysis showed that 1-NA-PP1
      was considerably more potent and showed distinct substituent effects at the
      pyrazolopyrimidine core. 1-NA-PP1 was cell-active, and potently blocked prostate
      cancer cell proliferation by inducing G2/M arrest. It also potently blocked the
      migration and invasion of prostate cancer cells, demonstrating promising
      anticancer activities on multiple fronts. Overexpression of PKD1 or PKD3 almost
      completely reversed the growth arrest and the inhibition of tumor cell invasion
      caused by 1-NA-PP1, indicating that its anti-proliferative and anti-invasive
      activities were mediated through the inhibition of PKD. Interestingly, a 12-fold
      increase in sensitivity to 1-NA-PP1 could be achieved by engineering a gatekeeper
      mutation in the active site of PKD1, suggesting that 1-NA-PP1 could be paired
      with the analog-sensitive PKD1(M659G) for dissecting PKD-specific functions and
      signaling pathways in various biological systems. 

PMID- 24086586
TI  - TRIM3 regulates the motility of the kinesin motor protein KIF21B.
AB  - Kinesin superfamily proteins (KIFs) are molecular motors that transport cellular
      cargo along the microtubule cytoskeleton. KIF21B is a neuronal kinesin that is
      highly enriched in dendrites. The regulation and specificity of microtubule
      transport involves the binding of motors to individual cargo adapters and
      accessory proteins. Moreover, posttranslational modifications of either the motor
      protein, their cargos or tubulin regulate motility, cargo recognition and the
      binding or unloading of cargos. Here we show that the ubiquitin E3 ligase TRIM3,
      also known as BERP, interacts with KIF21B via its RBCC domain. TRIM3 is found at
      intracellular and Golgi-derived vesicles and co-localizes with the KIF21B motor
      in neurons. Trim3 gene deletion in mice and TRIM3 overexpression in cultured
      neurons both suggested that the E3-ligase function of TRIM3 is not involved in
      KIF21B degradation, however TRIM3 depletion reduces the motility of the motor.
      Together, our data suggest that TRIM3 is a regulator in the modulation of KIF21B
      motor function. 

PMID- 24086587
TI  - Host response to respiratory bacterial pathogens as identified by integrated
      analysis of human gene expression data.
AB  - Respiratory bacterial pathogens are one of the leading causes of infectious death
      in the world and a major health concern complicated by the rise of multi
      antibiotic resistant strains. Therapeutics that modulate host genes essential for
      pathogen infectivity could potentially avoid multi-drug resistance and provide a
      wider scope of treatment options. Here, we perform an integrative analysis of
      published human gene expression data generated under challenges from the gram
      negative and Gram-positive bacteria pathogens, Pseudomonas aeruginosa and
      Streptococcus pneumoniae, respectively. We applied a previously described
      differential gene and pathway enrichment analysis pipeline to publicly available
      host mRNA GEO datasets resulting from exposure to bacterial infection. We found
      72 canonical human pathways common between four GEO datasets, representing P.
      aeruginosa and S. pneumoniae. Although the majority of these pathways are known
      to be involved with immune response, we found several interesting new
      interactions such as the SUMO1 pathway that might have a role in bacterial
      infections. Furthermore, 36 host-bacterial pathways were also shared with our
      previous results for respiratory virus host gene expression. Based on our pathway
      analysis we propose several drug-repurposing opportunities supported by the
      literature. 

PMID- 24086589
TI  - Loss of the histidine kinase DhkD results in mobile mounds during development of
      Dictyostelium discoideum.
AB  - BACKGROUND: Histidine kinases are receptors for sensing cellular and
      environmental signals, and in response to the appropriate cue they initiate
      phosphorelays that regulate the activity of response regulators. The
      Dictyostelium discoideum genome encodes 15 histidine kinases that function to
      regulate several processes during the multicellular developmental program,
      including the slug to culmination transition, osmoregulation, and spore
      differentiation. While there are many histidine kinases, there is only a single
      response regulator, RegA. Not surprisingly given the ubiquitous involvement of
      cAMP in numerous processes of development in Dictyostelium, RegA is a cAMP
      phosphodiesterase that is activated upon receiving phosphates through a
      phosphorelay. Hence, all of the histidine kinases characterized to date regulate
      developmental processes through modulating cAMP production. Here we investigate
      the function of the histidine kinase DhkD. PRINCIPAL FINDINGS: The dhkD gene was
      disrupted, and the resulting cells when developed gave a novel phenotype. Upon
      aggregation, which occurred without streaming, the mounds were motile, a
      phenotype termed the pollywog stage. The pollywog phenotype was dependent on a
      functional RegA. After a period of random migration, the pollywogs attempted to
      form fingers but mostly generated aberrant structures with no tips. While
      prestalk and prespore cell differentiation occurred with normal timing, proper
      patterning did not occur. In contrast, wild type mounds are not motile, and the
      cAMP chemotactic movement of cells within the mound facilitates proper prestalk
      and prespore patterning, tip formation, and the vertical elongation of the mound
      into a finger. CONCLUSIONS: We postulate that DhkD functions to ensure the proper
      cAMP distribution within mounds that in turn results in patterning, tip formation
      and the transition of mounds to fingers. In the absence of DhkD, aberrant cell
      movements in response to an altered cAMP distribution result in mound migration,
      a lack of proper patterning, and an inability to generate normal finger
      morphology.

PMID- 24086590
TI  - Variant callers for next-generation sequencing data: a comparison study.
AB  - Next generation sequencing (NGS) has been leading the genetic study of human
      disease into an era of unprecedented productivity. Many bioinformatics pipelines
      have been developed to call variants from NGS data. The performance of these
      pipelines depends crucially on the variant caller used and on the calling
      strategies implemented. We studied the performance of four prevailing callers,
      SAMtools, GATK, glftools and Atlas2, using single-sample and multiple-sample
      variant-calling strategies. Using the same aligner, BWA, we built four single
      sample and three multiple-sample calling pipelines and applied the pipelines to
      whole exome sequencing data taken from 20 individuals. We obtained genotypes
      generated by Illumina Infinium HumanExome v1.1 Beadchip for validation analysis
      and then used Sanger sequencing as a "gold-standard" method to resolve
      discrepancies for selected regions of high discordance. Finally, we compared the
      sensitivity of three of the single-sample calling pipelines using known simulated
      whole genome sequence data as a gold standard. Overall, for single-sample
      calling, the called variants were highly consistent across callers and the
      pairwise overlapping rate was about 0.9. Compared with other callers, GATK had
      the highest rediscovery rate (0.9969) and specificity (0.99996), and the Ti/Tv
      ratio out of GATK was closest to the expected value of 3.02. Multiple-sample
      calling increased the sensitivity. Results from the simulated data suggested that
      GATK outperformed SAMtools and glfSingle in sensitivity, especially for low
      coverage data. Further, for the selected discrepant regions evaluated by Sanger
      sequencing, variant genotypes called by exome sequencing versus the exome array
      were more accurate, although the average variant sensitivity and overall genotype
      consistency rate were as high as 95.87% and 99.82%, respectively. In conclusion,
      GATK showed several advantages over other variant callers for general purpose NGS
      analyses. The GATK pipelines we developed perform very well. 

PMID- 24086591
TI  - Canine chondrodysplasia caused by a truncating mutation in collagen-binding
      integrin alpha subunit 10.
AB  - The skeletal dysplasias are disorders of the bone and cartilage tissues.
      Similarly to humans, several dog breeds have been reported to suffer from
      different types of genetic skeletal disorders. We have studied the molecular
      genetic background of an autosomal recessive chondrodysplasia that affects the
      Norwegian Elkhound and Karelian Bear Dog breeds. The affected dogs suffer from
      disproportionate short stature dwarfism of varying severity. Through a genome
      wide approach, we mapped the chondrodysplasia locus to a 2-Mb region on canine
      chromosome 17 in nine affected and nine healthy Elkhounds (praw = 7.42*10(-6),
      pgenome-wide = 0.013). The associated locus contained a promising candidate gene,
      cartilage specific integrin alpha 10 (ITGA10), and mutation screening of its 30
      exons revealed a nonsense mutation in exon 16 (c.2083C>T; p.Arg695*) that
      segregated fully with the disease in both breeds (p = 2.5*10(-23)). A 24%
      mutation carrier frequency was indicated in NEs and an 8% frequency in KBDs. The
      ITGA10 gene product, integrin receptor alpha10-subunit combines into a collagen
      binding alpha10beta1 integrin receptor, which is expressed in cartilage
      chondrocytes and mediates chondrocyte-matrix interactions during endochondral
      ossification. As a consequence of the nonsense mutation, the alpha10-protein was
      not detected in the affected cartilage tissue. The canine phenotype highlights
      the importance of the alpha10beta1 integrin in bone growth, and the large animal
      model could be utilized to further delineate its specific functions. Finally,
      this study revealed a candidate gene for human chondrodysplasias and enabled the
      development of a genetic test for breeding purposes to eradicate the disease from
      the two dog breeds. 

PMID- 24086588
TI  - Role of HIV infection duration and CD4 cell level at initiation of combination
      anti-retroviral therapy on risk of failure.
AB  - BACKGROUND: The development of HIV drug resistance and subsequent virological
      failure are often cited as potential disadvantages of early cART initiation.
      However, their long-term probability is not known, and neither is the role of
      duration of infection at the time of initiation. METHODS: Patients enrolled in
      the UK Register of HIV seroconverters were followed-up from cART initiation to
      last HIV-RNA measurement. Through survival analysis we examined predictors of
      virologic failure (2HIV-RNA >=400 c/l while on cART) including CD4 count and HIV
      duration at initiation. We also estimated the cumulative probabilities of failure
      and drug resistance (from the available HIV nucleotide sequences) for early
      initiators (cART within 12 months of seroconversion). RESULTS: Of 1075 starting
      cART at a median (IQR) CD4 count 272 (190,370) cells/mm(3) and HIV duration 3
      (1,6) years, virological failure occurred in 163 (15%). Higher CD4 count at
      initiation, but not HIV infection duration at cART initiation, was independently
      associated with lower risk of failure (p=0.033 and 0.592 respectively). Among 230
      patients initiating cART early, 97 (42%) discontinued it after a median of 7
      months; cumulative probabilities of resistance and failure by 8 years were 7%
      (95% CI 4,11) and 19% (13,25), respectively. CONCLUSION: Although the rate of
      discontinuation of early cART in our cohort was high, the long-term rate of
      virological failure was low. Our data do not support early cART initiation being
      associated with increased risk of failure and drug resistance.

PMID- 24086593
TI  - Horizontal transfer of diatomaceous earth and botanical insecticides in the
      common bed bug, Cimex lectularius L.; hemiptera: cimicidae.
AB  - BACKGROUND: Horizontal transfer of insecticide occurs when insects contact or
      ingest an insecticide, return to an aggregation or a nest, and transfer the
      insecticide to other conspecific insects through contact. This phenomenon has
      been reported in a number of insects including social insects, however it has not
      been reported in bed bugs. Since horizontal transfer can facilitate the spread of
      insecticide into hard to reach spaces, it could contribute greatly to the
      management of these public health pests. METHODOLOGY/RESULTS: To demonstrate
      horizontal transfer of diatomaceous earth and botanical insecticides in C.
      lectularius, an exposed (donor) bed bug, following a 10-minute acquisition
      period, was placed with unexposed (recipient) bed bugs. Mortality data clearly
      demonstrates that diatomaceous earth (DE 51) was actively transferred from a
      single exposed bug to unexposed bugs in a concentration dependent manner. LC50
      values varied from 24.4 mg at 48 h to 5.1 mg at 216 h when a single exposed bed
      bug was placed with 5 unexposed bed bugs. LT50 values also exhibited a
      concentration response. LT50 values varied from 1.8 days to 8.4 days when a
      'donor' bug exposed to 20 and 5 mg of dust respectively was placed with 5
      'recipient' bugs. Dust was also actively transferred from adult bed bugs to the
      nymphs. In addition we observed horizontal transfer of botanical insecticides
      including neem, ryania, and rotenone to varying degrees. CONCLUSION/SIGNIFICANCE:
      Our data clearly demonstrate horizontal transfer of diatomaceous earth and
      botanical insecticides in the common bed bug, C. lectularius. Use of a
      fluorescent dust provided visual confirmation that contaminated bed bugs transfer
      dust to untreated bed bugs in harborage. This result is important because bedbugs
      live in hard-to-reach places and interaction between conspecifics can be
      exploited for delivery and dissemination of management products directed at this
      public health pest.

PMID- 24086592
TI  - Localization of HPV-18 E2 at mitochondrial membranes induces ROS release and
      modulates host cell metabolism.
AB  - Papillomavirus E2 proteins are predominantly retained in the nuclei of infected
      cells, but oncogenic (high-risk) HPV-18 and 16 E2 can shuttle between the host
      nucleus and cytoplasm. We show here that cytoplasmic HPV-18 E2 localizes to
      mitochondrial membranes, and independent mass spectrometry analyses of the E2
      interactome revealed association to the inner mitochondrial membrane including
      components of the respiratory chain. Mitochondrial E2 association modifies the
      cristae morphology when analyzed by electron microscopy and increases production
      of mitochondrial ROS. This ROS release does not induce apoptosis, but instead
      correlates with stabilization of HIF-1alpha and increased glycolysis. These
      mitochondrial functions are not shared by the non-oncogenic (low-risk) HPV-6 E2
      protein, suggesting that modification of cellular metabolism by high-risk HPV E2
      proteins could play a role in carcinogenesis by inducing the Warburg effect. 

PMID- 24086594
TI  - Associations of maternal and neonatal serum trace element concentrations with
      neonatal birth weight.
AB  - BACKGROUND: Trace elements play important nutritional roles in neonates. Our
      objective was to examine whether there are differences in maternal/neonatal serum
      trace element concentrations between mature infants and premature infants.
      METHODS: During 2012, 44 infants born at National Center for Global Health and
      Medicine, Tokyo, Japan, were enrolled. Serum samples were collected to measure
      serum iron, zinc, copper, and selenium concentrations 5 days after birth.
      Maternal serum samples were obtained before delivery and cord blood was taken at
      delivery to measure the same trace elements. We compared the results between term
      group whose birth weight were >=2500 g and gestational age were >=37 weeks and
      premature group whose birth weight were <2500 g or gestational age were <37
      weeks. Variables significantly different between two groups were included in
      linear regression models to identify significant predictors of birth weight.
      Values of P<0.05 were considered statistically significant. RESULTS: Serum
      selenium concentrations were lower in premature group than in term group (43.3+/
      7.0 ug/L vs. 52.0+/-8.9 ug/L, P = 0.001). Maternal serum selenium concentrations
      were also significantly lower in the mothers of premature group than in the
      mothers of term group (79.3+/-19.3 ug/L vs. 94.1+/-18.1 ug/L, P = 0.032). There
      were no significant differences in neonatal or maternal iron, zinc, or copper
      concentrations between two groups. Multivariate linear regression analysis showed
      that, except for gestational age, only maternal serum selenium was significantly
      associated with birth weight (P = 0.015). CONCLUSIONS: Serum selenium
      concentrations were lower in premature group and their mothers compared with the
      term group. The maternal serum selenium concentration was positively correlated
      with birth weight. These results suggest that maternal serum selenium
      concentration may influence neonatal birth weight.

PMID- 24086595
TI  - Age-dependent decline of endogenous pain control: exploring the effect of
      expectation and depression.
AB  - Although chronic pain affects all age ranges, it is particularly common in the
      elderly. One potential explanation for the high prevalence of chronic pain in the
      older population is impaired functioning of the descending pain inhibitory system
      which can be studied in humans using conditioned pain modulation (CPM) paradigms.
      In this study we investigated (i) the influence of age on CPM and (ii) the role
      of expectations, depression and gender as potential modulating variables of an
      age-related change in CPM. 64 healthy volunteers of three different age groups
      (young = 20-40 years, middle-aged = 41-60 years, old = 61-80 years) were studied
      using a classical CPM paradigm that combined moderate heat pain stimuli to the
      right forearm as test stimuli (TS) and immersion of the contralateral foot into
      ice water as the conditioning stimulus (CS). The CPM response showed an age
      dependent decline with strong CPM responses in young adults but no significant
      CPM responses in middle-aged and older adults. These age-related changes in CPM
      responses could not be explained by expectations of pain relief or depression.
      Furthermore, changes in CPM responses did not differ between men and women. Our
      results strongly support the notion of a genuine deterioration of descending pain
      inhibitory mechanisms with age. 

PMID- 24086596
TI  - Deadpan contributes to the robustness of the notch response.
AB  - Notch signaling regulates many fundamental events including lateral inhibition
      and boundary formation to generate very reproducible patterns in developing
      tissues. Its targets include genes of the bHLH hairy and Enhancer of split
      [E(spl)] family, which contribute to many of these developmental decisions. One
      member of this family in Drosophila, deadpan (dpn), was originally found to have
      functions independent of Notch in promoting neural development. Employing genome
      wide chromatin-immunoprecipitation we have identified several Notch responsive
      enhancers in dpn, demonstrating its direct regulation by Notch in a range of
      contexts including the Drosophila wing and eye. dpn expression largely overlaps
      that of several E(spl) genes and the combined knock-down leads to more severe
      phenotypes than either alone. In addition, Dpn contributes to the establishment
      of Cut expression at the wing dorsal-ventral (D/V) boundary; in its absence Cut
      expression is delayed. Furthermore, over-expression of Dpn inhibits expression
      from E(spl) gene enhancers, but not vice versa, suggesting that dpn contributes
      to a feed-back mechanism that limits E(spl) gene expression following Notch
      activation. Thus the combined actions of dpn and E(spl) appear to provide a
      mechanism that confers an initial rapid output from Notch activity which becomes
      self-limited via feedback between the targets. 

PMID- 24086597
TI  - Bioclimatic thresholds, thermal constants and survival of mealybug, Phenacoccus
      solenopsis (hemiptera: pseudococcidae) in response to constant temperatures on
      hibiscus.
AB  - Temperature-driven development and survival rates of the mealybug,
      Phenacoccussolenopsis Tinsley (Hemiptera: Pseudococcidae) were examined at nine
      constant temperatures (15, 20, 25, 27, 30, 32, 35 and 40 degrees C) on hibiscus
      (Hibiscusrosa -sinensis L.). Crawlers successfully completed development to adult
      stage between 15 and 35 degrees C, although their survival was affected at low
      temperatures. Two linear and four nonlinear models were fitted to describe
      developmental rates of P. solenopsis as a function of temperature, and for
      estimating thermal constants and bioclimatic thresholds (lower, optimum and upper
      temperature thresholds for development: Tmin, Topt and Tmax, respectively).
      Estimated thresholds between the two linear models were statistically similar.
      Ikemoto and Takai's linear model permitted testing the equivalence of lower
      developmental thresholds for life stages of P. solenopsis reared on two hosts,
      hibiscus and cotton. Thermal constants required for completion of cumulative
      development of female and male nymphs and for the whole generation were
      significantly lower on hibiscus (222.2, 237.0, 308.6 degree-days, respectively)
      compared to cotton. Three nonlinear models performed better in describing the
      developmental rate for immature instars and cumulative life stages of female and
      male and for generation based on goodness-of-fit criteria. The simplified beta
      type distribution function estimated Topt values closer to the observed maximum
      rates. Thermodynamic SSI model indicated no significant differences in the
      intrinsic optimum temperature estimates for different geographical populations of
      P. solenopsis. The estimated bioclimatic thresholds and the observed survival
      rates of P. solenopsis indicate the species to be high-temperature adaptive, and
      explained the field abundance of P. solenopsis on its host plants. 

PMID- 24086599
TI  - Equine multiple congenital ocular anomalies and silver coat colour result from
      the pleiotropic effects of mutant PMEL.
AB  - Equine Multiple Congenital Ocular Anomalies (MCOA) syndrome is a heritable eye
      disorder mainly affecting silver colored horses. Clinically, the disease
      manifests in two distinct classes depending on the horse genotype. Horses
      homozygous for the mutant allele present with a wide range of ocular defects,
      such as iris stromal hypoplasia, abnormal pectinate ligaments, megaloglobus,
      iridociliary cysts and cataracts. The phenotype of heterozygous horses is less
      severe and predominantly includes iridociliary cysts, which occasionally extend
      into the temporal retina. In order to determine the genetic cause of MCOA
      syndrome we sequenced the entire previously characterized 208 kilobase region on
      chromosome 6 in ten individuals; five MCOA affected horses from three different
      breeds, one horse with the intermediate Cyst phenotype and four unaffected
      controls from two different breeds. This was performed using Illumina TruSeq
      technology with paired-end reads. Through the systematic exclusion of all
      polymorphisms barring two SNPs in PMEL, a missense mutation previously reported
      to be associated with the silver coat colour and a non-conserved intronic SNP, we
      establish that this gene is responsible for MCOA syndrome. Our finding, together
      with recent advances that show aberrant protein function due to the coding
      mutation, suggests that the missense mutation is causative and has pleiotrophic
      effect, causing both the horse silver coat color and MCOA syndrome. 

PMID- 24086598
TI  - Conditional deletion of cytochrome p450 reductase in osteoprogenitor cells
      affects long bone and skull development in mice recapitulating antley-bixler
      syndrome: role of a redox enzyme in development.
AB  - NADPH-cytochrome P450 oxidoreductase (POR) is the primary electron donor for
      cytochromes P450, dehydrocholesterol reductase, heme oxygenase, and squalene
      monooxygenase. Human patients with specific mutations in POR exhibit severe
      developmental malformations including disordered steroidogenesis, sexual
      ambiguities and various bone defects, similar to those seen in patients with
      Antley-Bixler syndrome (ABS). To probe the role of POR during bone development,
      we generated a conditional knockout mouse (CKO) by cross breeding Por (lox/lox)
      and Dermo1 Cre mice. CKO mice were smaller than their littermate controls and
      exhibited significant craniofacial and long bone abnormalities. Differential
      staining of the CKO mice skull bases shows premature fusion of the
      sphenooccipital and basioccipital-exoccipital synchondroses. Class III
      malocclusion was noted in adult knockout mice with an unusual overgrowth of the
      lower incisors. Shorter long bones were observed along with a reduction in the
      bone volume fraction, measured by microCT, in the Por-deleted mice compared to
      age- and sex-matched littermate controls. Concerted up- or down-regulation of
      proteins in the FGF signaling pathway observed by immunohistochemistry in the
      tibia samples of CKO mice compared to wild type controls shows a decrease in the
      FGF signaling pathway. To our knowledge, this is the first report of a mouse
      model that recapitulates both skull and long bone defects upon Por deletion,
      offering an approach to study the sequelae of POR mutations. This unique model
      demonstrates that P450 metabolism in bone itself is potentially important for
      proper bone development, and that an apparent link exists between the POR and FGF
      signaling pathways, begging the question of how an oxidation-reduction
      flavoprotein affects developmental and cellular signaling processes. 

PMID- 24086600
TI  - BB0347, from the lyme disease spirochete Borrelia burgdorferi, is surface exposed
      and interacts with the CS1 heparin-binding domain of human fibronectin.
AB  - The causative agent of Lyme disease, Borrelia burgdorferi, codes for several
      known fibronectin-binding proteins. Fibronectin a common the target of diverse
      bacterial pathogens, and has been shown to be essential in allowing for the
      development of certain disease states. Another borrelial protein, BB0347, has
      sequence similarity with these other known fibronectin-binding proteins, and may
      be important in Lyme disease pathogenesis. Herein, we perform an initial
      characterization of BB0347 via the use of molecular and biochemical techniques.
      We found that BB0347 is expressed, produced, and presented on the outer surface
      of intact B. burgdorferi. We also demonstrate that BB0347 has the potential to be
      important in Lyme disease progression, and have begun to characterize the nature
      of the interaction between human fibronectin and this bacterial protein. Further
      work is needed to define the role of this protein in the borrelial infection
      process. 

PMID- 24086601
TI  - Pipoxolan ameliorates cerebral ischemia via inhibition of neuronal apoptosis and
      intimal hyperplasia through attenuation of VSMC migration and modulation of
      matrix metalloproteinase-2/9 and Ras/MEK/ERK signaling pathways.
AB  - Pipoxolan (PIPO) has anti-spasmodic effects, and it is used clinically to relieve
      smooth muscle spasms. Cerebrovascular disease is one of the leading causes of
      disability and death worldwide. The main aim of this study was to investigate the
      effects of PIPO on cerebral ischemia and vascular smooth muscle cell (VSMC)
      migration in vivo and in vitro. Cerebral infarction area, ratio of intima to
      media area (I/M ratio) and PCNA antibody staining of the carotid artery in vivo
      were measured. Cell viability of A7r5 cells, PDGF-BB-stimulated cell migration,
      and potential mechanisms of PIPO were evaluated by wound healing, transwell and
      Western blotting. PIPO (10 and 30 mg/kg p.o.) reduced: the cerebral infarction
      area; neurological deficit; TUNEL-positive cells; cleaved caspase 3-positive
      cells; intimal hyperplasia; and inhibited proliferating cell nuclear antigen
      (PCNA)-positive cells in rodents. PIPO (5, 10 and 15 uM) significantly inhibited
      PDGF-BB-stimulated VSMC migration and reduced Ras, MEK, and p-ERK levels.
      Moreover, PIPO decreased levels of matrix metalloproteinases -2 and -9 in PDGF-BB
      stimulated A7r5 cells. In summary, PIPO is protective in models of
      ischemia/reperfusion-induced cerebral infarction, carotid artery ligation-induced
      intimal hyperplasia and VSMC migration both in vivo and in vitro. PIPO could be
      potentially efficacious in preventing cerebrovascular and vascular diseases. 

PMID- 24086602
TI  - Moment-to-moment transfer of positive emotions in daily life predicts future
      course of depression in both general population and patient samples.
AB  - OBJECTIVE: Positive affect (PA) is closely linked to prevention of, and recovery
      from, depression. Previous studies have investigated PA reactivity to pleasant
      situations with respect to its protective properties in relation to mood
      disorder. The purpose of this study was to examine, and replicate, whether moment
      to-moment transfer of PA in daily life (PA persistence) is relevant to the
      prediction of future course of depression. METHOD: Individuals from three
      different studies (one general population sample (n=540), and two patient samples
      (n=43 and n=50) with matching controls (n=39 and n=21, respectively))
      participated in an Experience Sampling Method (ESM) study. Time-lagged multilevel
      analyses were used to assess the degree of transfer (or persistence) of momentary
      positive affective states over time, in relation to naturalistic outcome (study
      1) or treatment outcome (studies 2 and 3). Depressive symptoms were measured
      using the Symptom Checklist (SCL-90R) in sample 1 and the Hamilton Depression
      Rating Scale (HDRS) in samples 2 and 3. RESULTS: In study 1, participants with
      greater momentary PA persistence were less likely to show depressive symptoms at
      follow-up. In study 2, patients were more likely to respond to treatment if they
      displayed greater momentary PA persistence, particularly in those with recurrent
      depression. In study 3, patients with greater momentary PA persistence were
      similarly more likely to respond to treatment, especially when treated with
      imipramine rather than placebo. CONCLUSION: The ability to transfer PA from one
      moment to the next is an important factor in the prevention of and recovery from
      depressive symptoms. Patients with recurrent depression and those who receive
      antidepressants rather than placebo may benefit most from this effect. The
      results suggest that treatment-induced improvement in depression is mediated by
      increased levels of momentary transfer of PA in daily life, acquisition of which
      may be contingent on duration of exposure to depressive experience.

PMID- 24086603
TI  - Trends and significance of VRE colonization in the ICU: a meta-analysis of
      published studies.
AB  - BACKGROUND: The burden and significance of vancomycin-resistant enterococci (VRE)
      colonization in the ICU is not clearly understood. METHODS: We searched PubMed
      and EMBASE up to May 2013 for studies reporting the prevalence of VRE upon
      admission to the ICU and performed a meta-analysis to assess rates and trends of
      VRE colonization. We calculated the prevalence of VRE on admission and the
      acquisition (colonization and/or infection) rates to estimate time trends and the
      impact of colonization on ensuing VRE infections. FINDINGS: Across 37 studies
      (62,959 patients at risk), the estimated prevalence of VRE on admission to the
      ICU was 8.8% (7.1-10.6). Estimates were more consistent when cultures were
      obtained within 24 hours from admission. The VRE acquisition rate was 8.8% (95%
      CI 6.9-11.0) across 26 evaluable studies (35,364 patients at risk). Across US
      studies, VRE acquisition rate was 10.2% (95% CI 7.7-13.0) and demonstrated
      significant decline in annual trends. We used the US estimate of colonization on
      admission [12.3% (10.5-14.3)] to evaluate the impact of VRE colonization on
      admission in overall VRE prevalence. We demonstrated that VRE colonization on
      admission is a major determinant of the overall VRE burden in the ICU.
      Importantly, among colonized patients (including admitted and/or acquired cases)
      the VRE infection rates vary widely from 0-45% (with the risk of VRE bacteremia
      being reported from 0-16%) and <2% among those without a proven colonization.
      CONCLUSION: In summary, up to 10.6% of patients admitted in the ICU are colonized
      with VRE on admission and a similar percentage will acquire VRE during their ICU
      stay. Importantly, colonization on admission is a major determinant of VRE
      dynamics in the ICU and the risk of VRE-related infections is close related to
      colonization.

PMID- 24086604
TI  - Ectopic KIT copy number variation underlies impaired migration of primordial germ
      cells associated with gonadal hypoplasia in cattle (Bos taurus).
AB  - Impaired migration of primordial germ cells during embryonic development causes
      hereditary gonadal hypoplasia in both sexes of Northern Finncattle and Swedish
      Mountain cattle. The affected gonads exhibit a lack of or, in rare cases, a
      reduced number of germ cells. Most affected animals present left-sided gonadal
      hypoplasia. However, right-sided and bilateral cases are also found. This type of
      gonadal hypoplasia prevails in animals with white coat colour. Previous studies
      indicated that gonadal hypoplasia is inherited in an autosomal recessive fashion
      with incomplete penetrance. In order to identify genetic regions underlying
      gonadal hypoplasia, a genome-wide association study (GWAS) and a copy number
      variation (CNV) analysis were performed with 94 animals, including 21 affected
      animals, using bovine 777,962 SNP arrays. The GWAS and CNV results revealed two
      significantly associated regions on bovine chromosomes (BTA) 29 and 6,
      respectively (P=2.19 x 10(-13) and P=5.65 x 10(-6)). Subsequent cytogenetic and
      PCR analyses demonstrated that homozygosity of a ~500 kb chromosomal segment
      translocated from BTA6 to BTA29 (Cs29 allele) is the underlying genetic mechanism
      responsible for gonadal hypoplasia. The duplicated segment includes the KIT gene
      that is known to regulate the migration of germ cells and precursors of
      melanocytes. This duplication is also one of the two translocations associated
      with colour sidedness in various cattle breeds. 

PMID- 24086605
TI  - A wavelet-based noise reduction algorithm and its clinical evaluation in cochlear
      implants.
AB  - Noise reduction is often essential for cochlear implant (CI) recipients to
      achieve acceptable speech perception in noisy environments. Most noise reduction
      algorithms applied to audio signals are based on time-frequency representations
      of the input, such as the Fourier transform. Algorithms based on other
      representations may also be able to provide comparable or improved speech
      perception and listening quality improvements. In this paper, a noise reduction
      algorithm for CI sound processing is proposed based on the wavelet transform. The
      algorithm uses a dual-tree complex discrete wavelet transform followed by
      shrinkage of the wavelet coefficients based on a statistical estimation of the
      variance of the noise. The proposed noise reduction algorithm was evaluated by
      comparing its performance to those of many existing wavelet-based algorithms. The
      speech transmission index (STI) of the proposed algorithm is significantly better
      than other tested algorithms for the speech-weighted noise of different levels of
      signal to noise ratio. The effectiveness of the proposed system was clinically
      evaluated with CI recipients. A significant improvement in speech perception of
      1.9 dB was found on average in speech weighted noise. 

PMID- 24086606
TI  - Coral skeletons provide historical evidence of phosphorus runoff on the great
      barrier reef.
AB  - Recently, the inshore reefs of the Great Barrier Reef have declined rapidly
      because of deteriorating water quality. Increased catchment runoff is one
      potential culprit. The impacts of land-use on coral growth and reef health
      however are largely circumstantial due to limited long-term data on water quality
      and reef health. Here we use a 60 year coral core record to show that phosphorus
      contained in the skeletons (P/Ca) of long-lived, near-shore Porites corals on the
      Great Barrier Reef correlates with annual records of fertiliser application and
      particulate phosphorus loads in the adjacent catchment. Skeletal P/Ca also
      correlates with Ba/Ca, a proxy for fluvial sediment loading, again linking near
      shore phosphorus records with river runoff. Coral core records suggest that
      phosphorus levels increased 8 fold between 1949 and 2008 with the greatest levels
      coinciding with periods of high fertiliser-phosphorus use. Periods of high P/Ca
      correspond with intense agricultural activity and increased fertiliser
      application in the river catchment following agricultural expansion and
      replanting after cyclone damage. Our results demonstrate how coral P/Ca records
      can be used to assess terrestrial nutrient loading of vulnerable near-shore
      reefs. 

PMID- 24086608
TI  - Multiplex microsphere immunoassays for the detection of IgM and IgG to arboviral
      diseases.
AB  - Serodiagnosis of arthropod-borne viruses (arboviruses) at the Division of Vector
      Borne Diseases, CDC, employs a combination of individual enzyme-linked
      immunosorbent assays and microsphere immunoassays (MIAs) to test for IgM and IgG,
      followed by confirmatory plaque-reduction neutralization tests. Based upon the
      geographic origin of a sample, it may be tested concurrently for multiple
      arboviruses, which can be a cumbersome task. The advent of multiplexing
      represents an opportunity to streamline these types of assays; however, because
      serologic cross-reactivity of the arboviral antigens often confounds results, it
      is of interest to employ data analysis methods that address this issue. Here, we
      constructed 13-virus multiplexed IgM and IgG MIAs that included internal and
      external controls, based upon the Luminex platform. Results from samples tested
      using these methods were analyzed using 8 different statistical schemes to
      identify the best way to classify the data. Geographic batteries were also
      devised to serve as a more practical diagnostic format, and further samples were
      tested using the abbreviated multiplexes. Comparative error rates for the
      classification schemes identified a specific boosting method based on logistic
      regression "Logitboost" as the classification method of choice. When the data
      from all samples tested were combined into one set, error rates from the
      multiplex IgM and IgG MIAs were <5% for all geographic batteries. This work
      represents both the most comprehensive, validated multiplexing method for
      arboviruses to date, and also the most systematic attempt to determine the most
      useful classification method for use with these types of serologic tests. 

PMID- 24086609
TI  - Systematic application of DNA fiber-FISH technique in cotton.
AB  - Fluorescence in situ hybridization on extended DNA (fiber-FISH) is a powerful
      tool in high-resolution physical mapping. To introduce this technique into
      cotton, we developed the technique and tested it by deliberately mapping of
      telomere and 5S rDNA. Results showed that telomere-length ranged from 0.80 kb to
      37.86 kb in three species, G. hirsutum, G. herbaceum and G. arboreum. However,
      most of the telomeres (>91.0%) were below 10 kb. The length of 5S rDNA was
      revealed as 964 kb in G. herbaceum whereas, in G. arboreum, it was approximately
      three times longer (3.1 Mb). A fiber-FISH based immunofluorescence method was
      also described to assay the DNA methylation. Using this technique, we revealed
      that both telomere and 5S rDNA were methylated at different levels. In addition,
      we developed a BAC molecule-based fiber-FISH technique. Using this technique, we
      can precisely map BAC clones on each other and evaluated the size and location of
      overlapped regions. The development and application of fiber-FISH technique will
      facilitate high-resolution physical mapping and further directed sequencing
      projects for cotton. 

PMID- 24086607
TI  - Plasma IgG to linear epitopes in the V2 and V3 regions of HIV-1 gp120 correlate
      with a reduced risk of infection in the RV144 vaccine efficacy trial.
AB  - Neutralizing and non-neutralizing antibodies to linear epitopes on HIV-1 envelope
      glycoproteins have potential to mediate antiviral effector functions that could
      be beneficial to vaccine-induced protection. Here, plasma IgG responses were
      assessed in three HIV-1 gp120 vaccine efficacy trials (RV144, Vax003, Vax004) and
      in HIV-1-infected individuals by using arrays of overlapping peptides spanning
      the entire consensus gp160 of all major genetic subtypes and circulating
      recombinant forms (CRFs) of the virus. In RV144, where 31.2% efficacy against HIV
      1 infection was seen, dominant responses targeted the C1, V2, V3 and C5 regions
      of gp120. An analysis of RV144 case-control samples showed that IgG to V2
      CRF01_AE significantly inversely correlated with infection risk (OR= 0.54,
      p=0.0042), as did the response to other V2 subtypes (OR=0.60-0.63, p=0.016
      0.025). The response to V3 CRF01_AE also inversely correlated with infection risk
      but only in vaccine recipients who had lower levels of other antibodies,
      especially Env-specific plasma IgA (OR=0.49, p=0.007) and neutralizing antibodies
      (OR=0.5, p=0.008). Responses to C1 and C5 showed no significant correlation with
      infection risk. In Vax003 and Vax004, where no significant protection was seen,
      serum IgG responses targeted the same epitopes as in RV144 with the exception of
      an additional C1 reactivity in Vax003 and infrequent V2 reactivity in Vax004. In
      HIV-1 infected subjects, dominant responses targeted the V3 and C5 regions of
      gp120, as well as the immunodominant domain, heptad repeat 1 (HR-1) and membrane
      proximal external region (MPER) of gp41. These results highlight the presence of
      several dominant linear B cell epitopes on the HIV-1 envelope glycoproteins. They
      also generate the hypothesis that IgG to linear epitopes in the V2 and V3 regions
      of gp120 are part of a complex interplay of immune responses that contributed to
      protection in RV144. 

PMID- 24086610
TI  - Effect of type and concentration of ballasting particles on sinking rate of
      marine snow produced by the appendicularian Oikopleura dioica.
AB  - Ballast material (organic, opal, calcite, lithogenic) is suggested to affect
      sinking speed of aggregates in the ocean. Here, we tested this hypothesis by
      incubating appendicularians in suspensions of different algae or Saharan dust,
      and observing the sinking speed of the marine snow formed by their discarded
      houses. We show that calcite increases the sinking speeds of aggregates by ~100%
      and lithogenic material by ~150% while opal only has a minor effect. Furthermore
      the effect of ballast particle concentration was causing a 33 m d(-1) increase in
      sinking speed for a 5*10(5) um(3) ml(-1) increase in particle concentration, near
      independent on ballast type. We finally compare our observations to the
      literature and stress the need to generate aggregates similar to those in nature
      in order to get realistic estimates of the impact of ballast particles on sinking
      speeds. 

PMID- 24086611
TI  - Expression of HIV-1 Vpu leads to loss of the viral restriction factor
      CD317/Tetherin from lipid rafts and its enhanced lysosomal degradation.
AB  - CD317/tetherin (aka BST2 or HM1.24 antigen) is an interferon inducible membrane
      protein present in regions of the lipid bilayer enriched in sphingolipids and
      cholesterol (often termed lipid rafts). It has been implicated in an eclectic mix
      of cellular processes including, most notably, the retention of fully formed
      viral particles at the surface of cells infected with HIV and other enveloped
      viruses. Expression of the HIV viral accessory protein Vpu has been shown to lead
      to intracellular sequestration and degradation of tetherin, thereby counteracting
      the inhibition of viral release. There is evidence that tetherin interacts
      directly with Vpu, but it remains unclear where in the cell this interaction
      occurs or if Vpu expression affects the lipid raft localisation of tetherin. We
      have addressed these points using biochemical and cell imaging approaches focused
      on endogenous rather than ectopically over-expressed tetherin. We find i) no
      evidence for an interaction between Vpu and endogenous tetherin at the cell
      surface, ii) the vast majority of endogenous tetherin that is at the cell surface
      in control cells is in lipid rafts, iii) internalised tetherin is present in non
      raft fractions, iv) expression of Vpu in cells expressing endogenous tetherin
      leads to the loss of tetherin from lipid rafts, v) internalised tetherin enters
      early endosomes, and late endosomes, in both control cells and cells expressing
      Vpu, but the proportion of tetherin molecules destined for degradation rather
      than recycling is increased in cells expressing Vpu vi) lysosomes are the primary
      site for degradation of endogenous tetherin in cells expressing Vpu. Our studies
      underlie the importance of studying endogenous tetherin and let us propose a
      model in which Vpu intercepts newly internalised tetherin and diverts it for
      lysosomal destruction rather than recycling to the cell surface. 

PMID- 24086612
TI  - The human WBSCR22 protein is involved in the biogenesis of the 40S ribosomal
      subunits in mammalian cells.
AB  - The human WBSCR22 protein was previously shown to be up-regulated in invasive
      breast cancer and its ectopic expression enhances tumor cell survival in the
      vasculature. In the current study, we show that the WBSCR22 protein is important
      for cell growth. Knock-down of WBSCR22 with siRNA results in slower growth of
      WBSCR22-depleted cells. Treatment with siWBSCR22 causes defects in the processing
      of pre-rRNAs and reduces the level of free 40S ribosomal subunit, suggesting that
      WBSCR22 is involved in ribosome small subunit biosynthesis. The human WBSCR22
      partially complements the growth of WBSCR22 yeast homologue, bud23 deletion
      mutant suggesting that the human WBSCR22 is a functional homologue of yeast
      Bud23. WBSCR22 is localized throughout the cell nucleus and is not stably
      associated with ribosomal subunits within the cell nucleus. We also show that the
      WBSCR22 protein level is decreased in lymphoblastoid cell lines derived from
      William-Beuren Syndrome (WBS) patients compared to healthy controls. Our data
      suggest that the WBSCR22 protein is a ribosome biogenesis factor involved in the
      biosynthesis of 40S ribosomal particles in mammalian cells. 

PMID- 24086613
TI  - Increased sensitivity of the circadian system to temporal changes in the feeding
      regime of spontaneously hypertensive rats - a potential role for Bmal2 in the
      liver.
AB  - The mammalian timekeeping system generates circadian oscillations that
      rhythmically drive various functions in the body, including metabolic processes.
      In the liver, circadian clocks may respond both to actual feeding conditions and
      to the metabolic state. The temporal restriction of food availability to improper
      times of day (restricted feeding, RF) leads to the development of food
      anticipatory activity (FAA) and resets the hepatic clock accordingly. The aim of
      this study was to assess this response in a rat strain exhibiting complex
      pathophysiological symptoms involving spontaneous hypertension, an abnormal
      metabolic state and changes in the circadian system, i.e., in spontaneously
      hypertensive rats (SHR). The results revealed that SHR were more sensitive to RF
      compared with control rats, developing earlier and more pronounced FAA. Whereas
      in control rats, the RF only redistributed the activity profiles into two bouts
      (one corresponding to FAA and the other corresponding to the dark phase), in SHR
      the RF completely phase-advanced the locomotor activity according to the time of
      food presentation. The higher behavioral sensitivity to RF was correlated with
      larger phase advances of the hepatic clock in response to RF in SHR. Moreover, in
      contrast to the controls, RF did not suppress the amplitude of the hepatic clock
      oscillation in SHR. In the colon, no significant differences in response to RF
      between the two rat strains were detected. The results suggested the possible
      involvement of the Bmal2 gene in the higher sensitivity of the hepatic clock to
      RF in SHR because, in contrast to the Wistar rats, the rhythm of Bmal2 expression
      was advanced similarly to that of Bmal1 under RF. Altogether, the data
      demonstrate a higher behavioral and circadian responsiveness to RF in the rat
      strain with a cardiovascular and metabolic pathology and suggest a likely
      functional role for the Bmal2 gene within the circadian clock. 

PMID- 24086614
TI  - Retinal detachment in southwest Ethiopia: a hospital based prospective study.
AB  - PURPOSE: The incidence of retinal detachment in Blacks is generally considered to
      be low though there are few supporting studies in Africa. This study, thus, aimed
      at describing the clinical profile of patients with retinal detachment in
      Southwest Ethiopia. METHODS: A hospital-based study was done on all consecutive
      retinal detachment patients who presented to Jimma University Hospital over six
      months period. A semi-structured questionnaire was used to collect patients'
      sociodemographic characteristics and clinical history. Comprehensive anterior and
      posterior segment eye examinations were done and risk factors were sought for.
      Statistical tests were considered significant if P < 0.05. RESULTS: A total of 94
      eyes of 80 patients (1.5%) had retinal detachment (RD) and about 69% of patients
      were symptomatic for over a month before presentation. The mean age was 41.4
      years (SD +/-16.5). Fourteen patients (17.5%) had bilateral RD. At presentation,
      61 eyes (64.9%) were blind from RD and 11 (13.8%) patients were bilaterally blind
      from RD. Rhegmatogenous RD was seen in 55 eyes (58.5%) and tractional RD in 22
      eyes (23.4%). The most common risk factors were ocular trauma (32 eyes, 34.0%),
      myopia (23 eyes, 24.5%), posterior uveitis (13 eyes, 13.8%) and diabetic
      retinopathy (9 eyes, 9.6%). Most retinal breaks (25 eyes, 43.1%) were
      superotemporal and horse-shoe tear was the most common (19 eyes, 20.2%). Macula
      was off in 77 eyes (81.9%) and 38 eyes (69.1% of RRD eyes) had grade C
      proliferative vitreoretinopathy (PVR). Macular status was significantly
      associated with PVR (P=0.011), and duration of symptoms (RR=1.25, 95%CI: 1.059
      1.475, P=0.040). CONCLUSIONS: A significant numbers of patients with ocular
      problem had retinal detachment, and nearly two third of the patients presented
      late. Trauma and myopia were the most important risk factors. People should be
      educated to improve their health seeking behavior and use eye safety precautions
      to prevent ocular trauma.

PMID- 24086615
TI  - Estrogen receptor alpha and nuclear factor Y coordinately regulate the
      transcription of the SUMO-conjugating UBC9 gene in MCF-7 breast cancer cells.
AB  - UBC9 encodes a protein that conjugates small ubiquitin-related modifier (SUMO) to
      target proteins thereby changing their functions. Recently, it was noted that
      UBC9 expression and activity play a role in breast tumorigenesis and response to
      anticancer drugs. However, the underlying mechanism is poorly understood. To
      investigate the transcriptional regulation of the UBC9 gene, we identified and
      characterized its promoter and cis-elements. Promoter activity was tested using
      luciferase reporter assays. The binding of transcription factors to the promoter
      was detected by chromatin immunoprecipitation (ChIP), and their functional role
      was confirmed by siRNA knockdown. UBC9 mRNA and protein levels were measured by
      quantitative reverse transcription PCR and Western blot analysis, respectively.
      An increased expression of UBC9 mRNA and protein was found in MCF-7 breast cancer
      cells treated with 17beta-estradiol (E2). Analysis of various deletion mutants
      revealed a 137 bp fragment upstream of the transcription initiation site to be
      sufficient for reporter gene transcription. Mutations of putative estrogen
      receptor alpha (ER-alpha) (one imperfect estrogen response element, ERE) and/or
      nuclear factor Y (NF-Y) binding sites (two CCAAT boxes) markedly reduced promoter
      activity. Similar results were obtained in ER-negative MDA-MB-231 cells except
      that the ERE mutation did not affect promoter activity. Additionally, promoter
      activity was stimulated upon E2 treatment and overexpression of ER-alpha or NF-YA
      in MCF-7 cells. ChIP confirmed direct binding of both transcription factors to
      the UBC9 promoter in vivo. Furthermore, UBC9 expression was diminished by ER
      alpha and NF-Y siRNAs on the mRNA and protein levels. In conclusion, we
      identified the proximal UBC9 promoter and provided evidence that ER-alpha and NF
      Y regulate UBC9 expression on the transcriptional level in response to E2 in MCF
      7 cells. These findings may contribute to a better understanding of the
      regulation of UBC9 in ER-positive breast cancer and be useful for the development
      of cancer therapies targeting UBC9. 

PMID- 24086617
TI  - Complex population dynamics in mussels arising from density-linked stochasticity.
AB  - Population fluctuations are generally attributed to the deterministic
      consequences of strong non-linear interactions among organisms, or the effects of
      random stochastic environmental variation superimposed upon the deterministic
      skeleton describing population change. Analysis of the population dynamics of the
      mussel Mytilus californianus taken in 16 plots over 18-years found no evidence
      that these processes explained observed strong fluctuations. Instead, population
      fluctuations arose because environmental stochasticity varied with abundance,
      which we term density-linked stochasticity. This phenomenon arises from
      biologically relevant mechanisms: recruitment variation and transmission of
      disturbance among neighboring individuals. Density-linked stochasticity is
      probably present frequently in populations, as it arises naturally from several
      general ecological processes, including stage structure variation with density,
      ontogenetic niche shifts, and local transmission of stochastic perturbations.
      More thoroughly characterizing and interpreting deviations from the mean behavior
      of a system will lead to better ecological prediction and improved insight into
      the important processes affecting populations and ecosystems. 

PMID- 24086616
TI  - Beneficial effects of autologous bone marrow-derived mesenchymal stem cells in
      naturally occurring tendinopathy.
AB  - Tendon injuries are a common age-related degenerative condition where current
      treatment strategies fail to restore functionality and normal quality of life.
      This disease also occurs naturally in horses, with many similarities to human
      tendinopathy making it an ideal large animal model for human disease.
      Regenerative approaches are increasingly used to improve outcome involving
      mesenchymal stem cells (MSCs), supported by clinical data where injection of
      autologous bone marrow derived MSCs (BM-MSCs) suspended in marrow supernatant
      into injured tendons has halved the re-injury rate in racehorses. We hypothesized
      that stem cell therapy induces a matrix more closely resembling normal tendon
      than the fibrous scar tissue formed by natural repair. Twelve horses with career
      ending naturally-occurring superficial digital flexor tendon injury were
      allocated randomly to treatment and control groups. 1X10(7) autologous BM-MSCs
      suspended in 2 ml of marrow supernatant were implanted into the damaged tendon of
      the treated group. The control group received the same volume of saline.
      Following a 6 month exercise programme horses were euthanized and tendons
      assessed for structural stiffness by non-destructive mechanical testing and for
      morphological and molecular composition. BM-MSC treated tendons exhibited
      statistically significant improvements in key parameters compared to saline
      injected control tendons towards that of normal tendons and those in the
      contralateral limbs. Specifically, treated tendons had lower structural stiffness
      (p<0.05) although no significant difference in calculated modulus of elasticity,
      lower (improved) histological scoring of organisation (p<0.003) and crimp pattern
      (p<0.05), lower cellularity (p<0.007), DNA content (p<0.05), vascularity
      (p<0.03), water content (p<0.05), GAG content (p<0.05), and MMP-13 activity
      (p<0.02). Treatment with autologous MSCs in marrow supernatant therefore provides
      significant benefits compared to untreated tendon repair in enhancing
      normalisation of biomechanical, morphological, and compositional parameters.
      These data in natural disease, with no adverse findings, support the use of this
      treatment for human tendon injuries. 

PMID- 24086618
TI  - Development of a new resequencing pathogen microarray based assay for detection
      of broad-spectrum respiratory tract viruses in patients with community-acquired
      pneumonia.
AB  - A Resequencing Pathogen Microarray (RPM) is a single, highly multiplexed assay
      for detecting and differentiating similarly related pathogens by using closely
      overlapping probe sets to determine a target organism's nucleotide sequence. In
      this study, a new RPM (RPM-IVDC1) that consisted of 224-bp detector tiles
      corresponding to 9 influenza A subtypes, 11 rhinoviruses, 28 enteroviruses and 38
      other respiratory viruses was developed and optimized to provide individual and
      simultaneous detection sensitivities ranging from 15 to 750 genomic copies for 16
      common respiratory pathogens. A total of 110 consecutive patients with community
      acquired pneumonia (CAP) admitted to 5 district general hospitals in Beijing
      during a 1-year period were assessed using the new assay. Among the children
      (under age 5) and adult patients (above age 18), respiratory syncytial virus
      (RSV) and rhinovirus (RV) were the most common etiological agents, respectively,
      which is consistent with reference assays. Atypical pathogens that may cause CAP
      like illness, including rubella virus, measles virus, influenza type C virus,
      human herpesvirus (HHV) were also detected. The results show the capability of
      RPM-IVDC1 for the accurate detection and identification of multiple virus types,
      which may be of significant use in epidemic surveillance and outbreak
      investigations of atypical pathogens. 

PMID- 24086619
TI  - Comparative proteomic analysis of the stolon cold stress response between the C4
      perennial grass species Zoysia japonica and Zoysia metrella.
AB  - Zoysiagrass, the most cold-tolerant grass among the warm-season turfgrasses, is
      often used as a model species for isolating cellular components related to cold
      stress. To understand the proteomic responses to cold stress in zoysiagrass
      stolons, we extracted stolon proteins from Zoysiajaponica, cv. Meyer (cold
      tolerant) and Z. metrella, cv. Diamond (cold-sensitive), which were grown with or
      without cold treatment. Approximately 700 proteins were resolved on 2-DE gels,
      and 70 protein spots were differentially accumulated. We further observed that 45
      of the identified proteins participate in 10 metabolic pathways and cellular
      processes. A significantly greater number of proteins accumulated in the Meyer
      than in the Diamond and 15 increased proteins were detected only in the Meyer
      cultivar under cold stress. Furthermore, we propose a cold stress-responsive
      protein network composed of several different functional components that exhibits
      a balance between reactive oxygen species (ROS) production and scavenging,
      accelerated protein biosynthesis and proteolysis, reduced protein folding,
      enhanced photosynthesis, abundant energy supply and enhanced biosynthesis of
      carbohydrates and nucleotides. Generally, the cold-tolerant Meyer cultivar showed
      a greater ROS scavenging ability, more abundant energy supply and increased
      photosynthesis and protein synthesis than did the cold-sensitive Diamond
      cultivar, which may partly explain why Meyer is more cold tolerant. 

PMID- 24086620
TI  - Small molecule injection into single-cell C. elegans embryos via carbon
      reinforced nanopipettes.
AB  - The introduction of chemical inhibitors into living cells at specific times in
      development is a useful method for investigating the roles of specific proteins
      or cytoskeletal components in developmental processes. Some embryos, such as
      those of Caenorhabditis elegans, however, possess a tough eggshell that makes
      introducing drugs and other molecules into embryonic cells challenging. We have
      developed a procedure using carbon-reinforced nanopipettes (CRNPs) to deliver
      molecules into C. elegans embryos with high temporal control. The use of CRNPs
      allows for cellular manipulation to occur just subsequent to meiosis II with
      minimal damage to the embryo. We have used our technique to replicate classical
      experiments using latrunculin A to inhibit microfilaments and assess its effects
      on early polarity establishment. Our injections of latrunculin A confirm the
      necessity of microfilaments in establishing anterior-posterior polarity at this
      early stage, even when microtubules remain intact. Further, we find that
      latrunculin A treatment does not prevent association of PAR-2 or PAR-6 with the
      cell cortex. Our experiments demonstrate the application of carbon-reinforced
      nanopipettes to the study of one temporally-confined developmental event. The use
      of CRNPs to introduce molecules into the embryo should be applicable to
      investigations at later developmental stages as well as other cells with tough
      outer coverings. 

PMID- 24086621
TI  - Influence of acute complications on outcome 3 months after ischemic stroke.
AB  - BACKGROUND: Early medical complications are potentially modifiable factors
      influencing in-hospital outcome. We investigated the influence of acute
      complications on mortality and poor outcome 3 months after ischemic stroke.
      METHODS: Data were obtained from patients admitted to one of 13 stroke units of
      the Berlin Stroke Registry (BSR) who participated in a 3-months-follow up between
      June 2010 and September 2012. We examined the influence of the cumulative number
      of early in-hospital complications on mortality and poor outcome (death,
      disability or institutionalization) 3 months after stroke using multivariable
      logistic regression analyses and calculated attributable fractions to determine
      the impact of early complications on mortality and poor outcome. RESULTS: A total
      of 2349 ischemic stroke patients alive at discharge from acute care were included
      in the analysis. Older age, stroke severity, pre-stroke dependency and early
      complications were independent predictors of mortality 3 months after stroke.
      Poor outcome was independently associated with older age, stroke severity, pre
      stroke dependency, previous stroke and early complications. More than 60% of
      deaths and poor outcomes were attributed to age, pre-stroke dependency and stroke
      severity and in-hospital complications contributed to 12.3% of deaths and 9.1% of
      poor outcomes 3 months after stroke. CONCLUSION: The majority of deaths and poor
      outcomes after stroke were attributed to non-modifiable factors. However, early
      in-hospital complications significantly affect outcome in patients who survived
      the acute phase after stroke, underlining the need to improve prevention and
      treatment of complications in hospital.

PMID- 24086622
TI  - Jasmonate ZIM-domain (JAZ) protein regulates host and nonhost pathogen-induced
      cell death in tomato and Nicotiana benthamiana.
AB  - The nonhost-specific phytotoxin coronatine (COR) produced by several pathovars of
      Pseudomonas syringae functions as a jasmonic acid-isoleucine (JA-Ile) mimic and
      contributes to disease development by suppressing plant defense responses and
      inducing reactive oxygen species in chloroplast. It has been shown that the F-box
      protein CORONATINE INSENSITIVE 1 (COI1) is the receptor for COR and JA-Ile.
      JASMONATE ZIM DOMAIN (JAZ) proteins act as negative regulators for JA signaling
      in Arabidopsis. However, the physiological significance of JAZ proteins in P.
      syringae disease development and nonhost pathogen-induced hypersensitive response
      (HR) cell death is not completely understood. In this study, we identified JAZ
      genes from tomato, a host plant for P. syringae pv. tomato DC3000 (Pst DC3000),
      and examined their expression profiles in response to COR and pathogens. Most JAZ
      genes were induced by COR treatment or inoculation with COR-producing Pst DC3000,
      but not by the COR-defective mutant DB29. Tomato SlJAZ2, SlJAZ6 and SlJAZ7
      interacted with SlCOI1 in a COR-dependent manner. Using virus-induced gene
      silencing (VIGS), we demonstrated that SlJAZ2, SlJAZ6 and SlJAZ7 have no effect
      on COR-induced chlorosis in tomato and Nicotiana benthamiana. However, SlJAZ2-,
      SlJAZ6- and SlJAZ7-silenced tomato plants showed enhanced disease-associated cell
      death to Pst DC3000. Furthermore, we found delayed HR cell death in response to
      the nonhost pathogen Pst T1 or a pathogen-associated molecular pattern (PAMP),
      INF1, in SlJAZ2- and SlJAZ6-silenced N. benthamiana. These results suggest that
      tomato JAZ proteins regulate the progression of cell death during host and
      nonhost interactions. 

PMID- 24086623
TI  - Reduced serum levels of triglyceride, very low density lipoprotein cholesterol
      and apolipoprotein B in Parkinson's disease patients.
AB  - BACKGROUND: Previous studies have shown a lower incidence of stroke in
      Parkinson's disease (PD) patients. The role of the lipids and lipoproteins as
      risk factors for stroke is uncertain in the lower prevalence of stroke in PD
      patients. OBJECTIVES: To explore the lipids and lipoproteins serum levels in PD
      patients. METHODS: A retrospective study was performed on 110 PD patients (PD
      group), 130 controls with non-cerebrovascular neurological diseases (OD group),
      140 acute intracerebral hemorrhage patients (ICH group) and 140 acute cerebral
      infarction patients (CI group). The records about serum levels of lipids and
      lipoproteins were analyzed. RESULTS: There were significant differences for the
      serum level of triglyceride (F = 5.031, p=0.002), very low density lipoprotein
      cholesterol (F = 5.313, p=0.001), apolipoprotein B (F = 16.038, p<0.0001) in the
      four groups. PD group had a significantly lower serum level of triglyceride (TG)
      than the OD (p=0.032), ICH (p=0.00047) and CI (p=0.001) groups. Very low density
      lipoprotein cholesterol (VLDL-C) serum level was significantly lower in PD group
      than in OD (p=0.039), ICH (p=0.00021) and CI (p=0.001) groups. There was a
      significantly lower serum level of apolipoprotein B (apo B) in PD group than in
      OD (p=0.002), ICH (p<0.0001) and CI (p<0.0001) groups. CONCLUSIONS: There are
      reduced serum levels of TG, VLDL-C and apo B in PD patients, which may be related
      to the decreased prevalence of stroke in PD patients.

PMID- 24086624
TI  - Amyloid beta inhibits olfactory bulb activity and the ability to smell.
AB  - Early olfactory dysfunction has been consistently reported in both Alzheimer's
      disease (AD) and in transgenic mice that reproduce some features of this disease.
      In AD transgenic mice, alteration in olfaction has been associated with increased
      levels of soluble amyloid beta protein (Abeta) as well as with alterations in the
      oscillatory network activity recorded in the olfactory bulb (OB) and in the
      piriform cortex. However, since AD is a multifactorial disease and transgenic
      mice suffer a variety of adaptive changes, it is still unknown if soluble Abeta,
      by itself, is responsible for OB dysfunction both at electrophysiological and
      behavioral levels. Thus, here we tested whether or not Abeta directly affects OB
      network activity in vitro in slices obtained from mice and rats and if it affects
      olfactory ability in these rodents. Our results show that Abeta decreases, in a
      concentration- and time-dependent manner, the network activity of OB slices at
      clinically relevant concentrations (low nM) and in a reversible manner. Moreover,
      we found that intrabulbar injection of Abeta decreases the olfactory ability of
      rodents two weeks after application, an effect that is not related to alterations
      in motor performance or motivation to seek food and that correlates with the
      presence of Abeta deposits. Our results indicate that Abeta disrupts, at
      clinically relevant concentrations, the network activity of the OB in vitro and
      can trigger a disruption in olfaction. These findings open the possibility of
      exploring the cellular mechanisms involved in early pathological AD as an
      approach to reduce or halt its progress. 

PMID- 24086625
TI  - Silencing of doublecortin-like (DCL) results in decreased mitochondrial activity
      and delayed neuroblastoma tumor growth.
AB  - Doublecortin-like (DCL) is a microtubule-binding protein crucial for
      neuroblastoma (NB) cell proliferation. We have investigated whether the anti
      proliferative effect of DCL knockdown is linked to reduced mitochondrial
      activity. We found a delay in tumor development after DCL knockdown in vivo in
      doxycycline-inducible NB tumor xenografts. To understand the mechanisms
      underlying this tumor growth retardation we performed a series of in vitro
      experiments in NB cell lines. DCL colocalizes with mitochondria, interacts with
      the mitochondrial outer membrane protein OMP25/ SYNJ2BP and DCL knockdown results
      in decreased expression of genes involved in oxidative phosphorylation. Moreover,
      DCL knockdown decreases cytochrome c oxidase activity and ATP synthesis. We
      identified the C-terminal Serine/Proline-rich domain and the second microtubule
      binding area as crucial DCL domains for the regulation of cytochrome c oxidase
      activity and ATP synthesis. Furthermore, DCL knockdown causes a significant
      reduction in the proliferation rate of NB cells under an energetic challenge
      induced by low glucose availability. Together with our previous studies, our
      results corroborate DCL as a key player in NB tumor growth in which DCL controls
      not only mitotic spindle formation and the stabilization of the microtubule
      cytoskeleton, but also regulates mitochondrial activity and energy availability,
      which makes DCL a promising molecular target for NB therapy. 

PMID- 24086626
TI  - Effects of low-dose microwave on healing of fractures with titanium alloy
      internal fixation: an experimental study in a rabbit model.
AB  - BACKGROUND: Microwave is a method for improving fracture repair. However, one of
      the contraindications for microwave treatment listed in the literature is
      surgically implanted metal plates in the treatment field. The reason is that the
      reflection of electromagnetic waves and the eddy current stimulated by microwave
      would increase the temperature of magnetic implants and cause heat damage in
      tissues. Comparing with traditional medical stainless steel, titanium alloy is a
      kind of medical implants with low magnetic permeability and electric
      conductivity. But the effects of microwave treatment on fracture with titanium
      alloy internal fixation in vivo were not reported. The aim of this article was to
      evaluate the security and effects of microwave on healing of a fracture with
      titanium alloy internal fixation. METHODS: Titanium alloy internal fixation
      systems were implanted in New Zealand rabbits with a 3.0 mm bone defect in the
      middle of femur. We applied a 30-day microwave treatment (2,450MHz, 25W, 10 min
      per day) to the fracture 3 days after operation. Temperature changes of muscle
      tissues around implants were measured during the irradiation. Normalized
      radiographic density of the fracture gap was measured on the 10th day and 30th
      day of the microwave treatment. All of the animals were killed after 10 and 30
      days microwave treatment with histologic and histomorphometric examinations
      performed on the harvested tissues. FINDINGS: The temperatures did not increase
      significantly in animals with titanium alloy implants. The security of microwave
      treatment was also supported by histology of muscles, nerve and bone around the
      implants. Radiographic assessment, histologic and histomorphometric examinations
      revealed significant improvement in the healing bone. CONCLUSION: Our results
      suggest that, in the healing of fracture with titanium alloy internal fixation, a
      low dose of microwave treatment may be a promising method.

PMID- 24086627
TI  - Are they really lost? "true" status and reasons for treatment discontinuation
      among HIV infected patients on antiretroviral therapy considered lost to follow
      up in Urban Malawi.
AB  - INTRODUCTION: Patients who are lost to follow-up (LTFU) while on antiretroviral
      therapy (ART) pose challenges to the long-term success of ART programs. We
      describe the extent to which patients considered LTFU are misclassified as true
      disengagement from care when they are still alive on ART and explain reasons for
      ART discontinuation using our active tracing program to further improve ART
      retention programs and policies. METHODS: We identified adult ART patients who
      missed clinic appointment by more than 3 weeks between January 2006 and December
      2010, assuming that such patients would miss their doses of antiretroviral drugs.
      Patients considered LTFU who consented during ART registration were traced by
      phone or home visits; true ART status after tracing was documented. Reasons for
      ART discontinuation were also recorded for those who stopped ART. RESULTS: Of the
      4,560 suspected LTFU cases, 1,384 (30%) could not be traced. Of the 3,176
      successfully traced patients, 952 (30%) were dead and 2,224 (70%) were alive, of
      which 2,183 (99.5%) started ART according to phone-based self-reports or physical
      verification during in-person interviews. Of those who started ART, 957 (44%)
      stopped ART and 1,226 (56%) reported still taking ART at the time of interview by
      sourcing drugs from another clinic, using alternative ART sources or making brief
      ART interruptions. Among 940 cases with reasons for ART discontinuations, failure
      to remember (17%), too weak/sick (12%), travel (46%), and lack of transport to
      the clinic (16%) were frequently cited; reasons differed by gender. CONCLUSION:
      The LTFU category comprises sizeable proportions of patients still taking ART
      that may potentially bias retention estimates and misdirect resources at the
      clinic and national levels if not properly accounted for. Clinics should consider
      further decentralization efforts, increasing drug allocations for frequent
      travels, and improving communication on patient transfers between clinics to
      increase retention and adherence.

PMID- 24086628
TI  - Evolutionary reconstruction and population genetics analysis of aurora kinases.
AB  - BACKGROUND: Aurora kinases belong to the highly conserved kinase family and play
      a vital role in cell cycle regulation. The structure and function of these
      kinases are inter-related and sometimes they also act as substitutes in case of
      knockdown of other aurora kinases. METHOD: In this work we carried out the
      evolutionary reconstruction and population genetic studies of aurora kinase
      proteins. Substitution saturation test, CAI (Codon adaptation index), gene
      expression and RSCU (Relative synonymous codon usage) values were computed for
      all the three aurora kinases. Linear regression method was used to check the
      dependency of gene expression on their CAI values. RESULTS: The results suggested
      that aurora-B and aurora-C has shown convergence in their evolutionary pathway.
      Moreover, the aurora-A I57V mutation showed high penetrance in human population
      and exist at very high frequency (84.4%) when compared to the native residue
      (15.6%). The mutation showed notable range of functional gain and seemed to be
      promising for the evolution of aurora-A function. Mutant allele might also become
      a challenging prospect for understanding the pattern of evolution followed by
      cell cycle kinases. CONCLUSION: The overall result suggested that the aurora-A is
      currently under the evolutionary transition and to determine the functional
      significance of the mutation further investigation are required.

PMID- 24086629
TI  - AQP9 expression in glioblastoma multiforme tumors is limited to a small
      population of astrocytic cells and CD15(+)/CalB(+) leukocytes.
AB  - Aquaporin-9 (AQP9) is a membrane protein channel that is permeable to a range of
      small solutes, including glycerol, urea and nucleobases. Expression of AQP9 in
      normal brain is limited, while widespread AQP9 expression has previously been
      reported in human glioblastoma. However, the specific cellular expression of AQP9
      in glioblastoma remains unclear. In this study, we have examined microarrays to
      corroborate AQP9 mRNA expression in glioma. These analyses suggested that AQP9
      mRNA expression in glioblastoma is primarily explained by tumor infiltration with
      AQP9 expressing leukocytes. Immunolabeling confirmed that within tumor regions,
      AQP9 was expressed in CD15(+) and Calgranulin B(+) leukocytes, but also in larger
      cells that morphologically resembled glioma cells. Specificity of immunoreagents
      was tested in recombinant cell lines, leukocyte preparations, and sections of
      normal human brain and liver tissue. Apparent AQP9(+) glioma cells were
      frequently observed in proximity to blood vessels, where brain tumor stem cells
      have been observed previously. A fraction of these larger AQP9 expressing cells
      co-expressed the differentiated astrocyte marker GFAP. AQP9 expressing glioma
      cells were negative for the brain tumor stem cell marker CD15, but were observed
      in proximity to CD15(+) glioma cells. AQP9 expression may therefore require
      signals of the perivascular tumor environment or alternatively it may be
      restricted to a population of glioma stem cell early progenitor cells. 

PMID- 24086630
TI  - Ocular allergy modulation to hi-dose antigen sensitization is a Treg-dependent
      process.
AB  - A reproducible method to inhibit allergic immune responses is accomplished with
      hi-dose Ag sensitization, via intraperitoneal (IP) injection. However, the role
      of CD4+ CD25+ FoxP3+ T regulatory cells (Treg) in this process is unknown, as is
      whether such modulation extends to ocular allergy. We therefore determined herein
      whether hi-dose sensitization modulates ocular allergy, and whether CD4+ CD25+
      FoxP3+ Treg are involved. C57BL/6 mice were IP sensitized via low-dose (100 ug)
      versus hi-dose (1000 ug) ovalbumin (OVA), in aluminum hydroxide (1 mg) and
      pertussis-toxin (300 ng). Other mice received anti-CD25 Ab (PC61) to ablate Treg
      during sensitization. In another experiment, Treg from hi-dose sensitized mice
      were adoptively transferred into low-dose sensitized mice. Once daily OVA
      challenges were administered. Clinical signs, IgE, T cell cytokines, and
      eosinophils were assessed. Data revealed that hi-dose, but not low-dose,
      sensitization led to allergy modulation, indicated by decreased clinical signs,
      serum IgE levels, Th2 recall responses, and eosinophil recruitment. T cells from
      hi-dose sensitized mice showed a robust increase in TGF-b production, and Treg
      from these mice were able to efficiently suppress effector T cell proliferation
      in vitro. In addition, in vivo Treg ablation in hi-dose sensitized mice revoked
      allergy modulation. Lastly, Treg from hi-dose sensitized mice were able to
      adoptively transfer allergy modulation to their low-dose sensitized counterparts.
      Collectively, these findings indicate that modulation to hi-dose sensitization,
      which is extended to ocular allergy, occurs in a Treg-dependent manner. In
      addition, our data suggest that hi-dose sensitization may henceforth facilitate
      the further examination of CD4+ CD25+ FoxP3+ Treg in allergic disease. 

PMID- 24086631
TI  - CCBE1 mutation in two siblings, one manifesting lymphedema-cholestasis syndrome,
      and the other, fetal hydrops.
AB  - BACKGROUND: Lymphedema-cholestasis syndrome (LCS; Aagenaes syndrome) is a rare
      autosomal recessive disorder, characterized by 1) neonatal intrahepatic
      cholestasis, often lessening and becoming intermittent with age, and 2) severe
      chronic lymphedema, mainly lower limb. LCS was originally described in a
      Norwegian kindred in which a locus, LCS1, was mapped to a 6.6cM region on
      chromosome 15. Mutations in CCBE1 on chromosome 18 have been reported in some
      cases of lymphatic dysplasia, but not in LCS. METHODS: Consanguineous parents of
      Mexican ancestry had a child with LCS who did not exhibit extended homozygosity
      in the LCS1 region. A subsequent pregnancy was electively terminated due to fetal
      hydrops. We performed whole-genome single nucleotide polymorphism genotyping to
      identify regions of homozygosity in these siblings, and sequenced promising
      candidate genes. RESULTS: Both siblings harbored a homozygous mutation in CCBE1,
      c.398 T>C, predicted to result in the missense change p.L133P. Regions containing
      known 'cholestasis genes' did not demonstrate homozygosity in the LCS patient.
      CONCLUSIONS: Mutations in CCBE1 may yield a phenotype not only of lymphatic
      dysplasia, but also of LCS or fetal hydrops; however, the possibility that the
      sibling with LCS also carries a homozygous mutation in an unidentified gene
      influencing cholestasis cannot be excluded.

PMID- 24086632
TI  - Ectopic expression of WUS in hypocotyl promotes cell division via GRP23 in
      Arabidopsis.
AB  - WUSCHEL (WUS) is essential for preventing stem cell differentiation in
      Arabidopsis. Here we report that in addition to its functions in meristematic
      stem cell maintenance, WUS is involved in the regulation of cell division. The
      WUS gain-of-function mutant, stem ectopic flowers (sef), displayed elongated
      hypocotyls, whereas the loss-of-function wus-1 mutant had shortened hypocotyls.
      The long hypocotyl in sef was due to the presence of more cells, rather than
      increased cell elongation. Microscopic observation, flow cytometry assays,
      quantitative RT-PCR (qRT-PCR), and histochemical staining of CycB1;1::GUS
      supported the hypothesis that ectopic cell division occurred in the sef
      hypocotyls after germination. Both immunoblot and qRT-PCR results showed that WUS
      was ectopically expressed in sef hypocotyls. Luciferase activity, chromatin
      immunoprecipitation (ChIP) and electrophoretic mobility shift assay (EMSA) showed
      that GLUTAMINE-RICH PROTEIN 23 (GRP23) expression can be activated by WUS and
      that GRP23 is a direct target gene of WUS. The phenotypes of 35S::GRP23 plants
      and GRP23 knockdown lines supported the notion that GRP23 mediates the effects of
      WUS on hypocotyl length. Together, our data suggest that ectopic expression of
      WUS in hypocotyl controls cell division through its target gene GRP23. 

PMID- 24086633
TI  - Spinal deformity in aged zebrafish is accompanied by degenerative changes to
      their vertebrae that resemble osteoarthritis.
AB  - Age-related degenerative changes within the vertebral column are a significant
      cause of morbidity with considerable socio-economic impact worldwide. An improved
      understanding of these changes through the development of experimental models may
      lead to improvements in existing clinical treatment options. The zebrafish is a
      well-established model for the study of skeletogenesis with significant potential
      in gerontological research. With advancing age, zebrafish frequently develop
      gross deformities of their vertebral column, previously ascribed to reduced trunk
      muscle tone. In this study, we assess degenerative changes specifically within
      the bone and cartilage of the vertebral column of zebrafish at 1, 2 and 3-years
      of age. We show increased frequency and severity of spinal deformities/curvatures
      with age. Underlying the most severe phenotypes are partial or complete vertebral
      dislocations and focal thickening of the vertebral bone at the joint margins.
      MicroCT examination demonstrates small defects, fractures and morphological
      evidence suggestive of bone erosion and remodeling (i.e. osteophytes) within the
      vertebrae during aging, but no significant change in bone density. Light and
      electron microscopic examination reveal striking age-related changes in cell
      morphology, suggestive of chondroptosis, and tissue remodelling of the vertebral
      cartilage, particularly within the pericellular micro-environment.
      Glycosaminoglycan analysis of the vertebral column by HPLC demonstrates a
      consistent, age-related increase in the yield of total chondroitin sulfate
      disaccharide, but no change in sulfation pattern, supported by
      immunohistochemical analysis. Immunohistochemistry strongly identifies all three
      chondroitin/dermatan sulphate isoforms (C-0-S, C-4-S/DS and C-6-S) within the
      vertebral cartilage, particularly within the pericellular micro-environment. In
      contrast, keratan sulfate immunolocalises specifically with the notochordal
      tissue of the intervertebral disc, and its labelling diminishes with age. In
      summary, these observations raise the prospect that zebrafish, in addition to
      modelling skeletal development, may have utility in modelling age-related
      degenerative changes that affect the skeleton during senescence. 

PMID- 24086634
TI  - Seasonal dynamics of fish assemblages on breakwaters and natural rocky reefs in a
      temperate estuary: consistent assemblage differences driven by sub-adults.
AB  - Development of infrastructure around cities is rapidly increasing the amount of
      artificial substrate (termed artificial reef, 'AR') in coastal marine habitats.
      However, effects of ARs on marine communities remain unknown, because it is
      unclear whether ARs can maintain similar communities to natural reefs. We
      investigated whether well-established (> 30 years old) breakwaters could
      consistently approximate fish assemblages on interspersed rocky reefs in a
      temperate estuary over 6 consecutive seasons using regular visual surveys between
      June 2009 (winter) and November 2010 (spring). We examined whether assemblage
      differences between reef types were driven by differences in juvenile
      recruitment, or were related to differences in older life-stages. Assemblages on
      both reef types were dominated by juveniles (61% of individuals) and sub-adults
      (34% of individuals). Seasonal fluctuations in assemblage parameters (species
      richness, diversity, sub-adult abundance) were similar between reef types, and
      levels of species diversity and assemblage composition were generally comparable.
      However, abundance and species richness were consistently higher (1.9-7.6 and 1.3
      2.6 times, respectively) on breakwaters. These assemblage differences could not
      be explained by differences in juvenile recruitment, with seasonal patterns of
      recruitment and juvenile species found to be similar between reef types. In
      contrast, abundances of sub-adults were consistently higher (1.1-12 times) at
      breakwaters, and assemblage differences appeared to be driven by this life-stage.
      Our results indicate that breakwaters in temperate estuaries are capable of
      supporting abundant and diverse fish assemblages with similar recruitment process
      to natural reefs. However, breakwaters may not approximate all aspects of natural
      assemblage structure, with differences maintained by a single-life stage in some
      cases. 

PMID- 24086635
TI  - A Genomic redefinition of Pseudomonas avellanae species.
AB  - The circumscription of bacterial species is a complex task. So far, DNA-DNA
      hybridization (DDH), 16S rRNA gene sequencing, and multiocus sequence typing
      analysis (MLSA) are currently the preferred techniques for their genetic
      determination. However, the average nucleotide identity (ANI) analysis of
      conserved and shared genes between two bacterial strains based on the pair-wise
      genome comparisons, with support of the tetranucleotide frequency correlation
      coefficients (TETRA) value, has recently been proposed as a reliable substitute
      for DDH. The species demarcation boundary has been set to a value of 95-96% of
      the ANI identity, with further confirmation through the assessment of the
      corresponding TETRA value. In this study, we performed a genome-wide MLSA of 14
      phytopathogenic pseudomonads genomes, and assessed the ANI and TETRA values of 27
      genomes, representing seven out of the nine genomospecies of Pseudomonas spp.
      sensu Gardan et alii, and their phylogenetic relationships using maximum
      likelihood and Bayesian approaches. The results demonstrate the existence of a
      well demarcated genomic cluster that includes strains classified as P. avellanae,
      P. syringae pv. theae, P. s. pv. actinidiae and one P. s. pv. morsprunorum strain
      all belonging to the single species P. avellanae. In addition, when compared with
      P. avellanae, five strains of P. s. pv. tomato, including the model strain
      DC3000, and one P. s. pv. lachrymans strain, appear as very closely related to P.
      avellanae, with ANI values of nearly 96% as confirmed by the TETRA analysis.
      Conversely, one representative strain, previously classified as P. avellanae and
      isolated in central Italy, is a genuine member of the P. syringae species complex
      and can be defined as P. s. pv. avellanae. Currently. The core and pan genomes of
      P. avellanae species consist of 3,995 and 5,410 putative protein-coding genes,
      respectively. 

PMID- 24086636
TI  - Von Willebrand factor inhibits mature smooth muscle gene expression through
      impairment of Notch signaling.
AB  - Von Willebrand factor (vWF), a hemostatic protein normally synthesized and stored
      by endothelial cells and platelets, has been localized beyond the endothelium in
      vascular disease states. Previous studies have implicated potential non
      hemostatic functions of vWF, but signaling mechanisms underlying its effects are
      currently undefined. We present evidence that vWF breaches the endothelium and is
      expressed in a transmural distribution pattern in cerebral small vessel disease
      (SVD). To determine the potential molecular consequences of vWF permeation into
      the vessel wall, we also tested whether vWF impairs Notch regulation of key
      smooth muscle marker genes. In a co-culture system using Notch ligand expressing
      cells to stimulate Notch in A7R5 cells, vWF strongly inhibited both the Notch
      pathway and the activation of mature smooth muscle gene promoters. Similar
      repressive effects were observed in primary human cerebral vascular smooth muscle
      cells. Expression of the intracellular domain of NOTCH3 allowed cells to bypass
      the inhibitory effects of vWF. Moreover, vWF forms molecular complexes with all
      four mammalian Notch ectodomains, suggesting a novel function of vWF as an
      extracellular inhibitor of Notch signaling. In sum, these studies demonstrate vWF
      in the vessel wall as a common feature of cerebral SVD; furthermore, we provide a
      plausible mechanism by which non-hemostatic vWF may play a novel role in the
      promotion of vascular disease. 

PMID- 24086637
TI  - Conditional and specific cell ablation in the marine annelid Platynereis
      dumerilii.
AB  - The marine annelid Platynereis dumerilii has become a model system for evo-devo,
      neurobiology and marine biology. The functional assessment of its cell types,
      however, has so far been very limited. Here we report on the establishment of a
      generally applicable, cell type specific ablation technique to overcome this
      restriction. Using a transgenic strain expressing the bacterial enzyme
      nitroreductase (ntr) under the control of the worm's r-opsin1 locus, we show that
      the demarcated photoreceptor cells can be specifically ablated by the addition of
      the prodrug metronidazole (mtz). TUNEL staining indicates that ntr expressing
      cells undergo apoptotic cell death. As we used a transgenic strain co-expressing
      ntr with enhanced green fluorescent protein (egfp) coding sequence, we were able
      to validate the ablation of photoreceptors not only in fixed tissue, using r
      opsin1 riboprobes, but also by monitoring eGFP+ cells in live animals. The
      specificity of the ablation was demonstrated by the normal presence of the eye
      pigment cells, as well as of neuronal markers expressed in other cells of the
      brain, such as phc2, tyrosine hydroxylase and brn1/2/4. Additional analyses of
      the position of DAPI stained nuclei, the brain's overall neuronal scaffold, as
      well as the positions and projections of serotonergic neurons further confirmed
      that mtz treatment did not induce general abnormalities in the worm's brain. As
      the prodrug is administered by adding it to the water, targeted ablation of
      specific cell types can be achieved throughout the life of the animal. We show
      that ablation conditions need to be adjusted to the size of the worms, likely due
      to differences in the penetration of the prodrug, and establish ablation
      conditions for worms containing 10 to 55 segments. Our results establish mtz/ntr
      mediated conditional cell ablation as a powerful functional tool in Platynereis. 

PMID- 24086638
TI  - Polyhydroxybutyrate targets mammalian mitochondria and increases permeability of
      plasmalemmal and mitochondrial membranes.
AB  - Poly(3-hydroxybutyrate) (PHB) is a polyester of 3-hydroxybutyric acid (HB) that
      is ubiquitously present in all organisms. In higher eukaryotes PHB is found in
      the length of 10 to 100 HB units and can be present in free form as well as in
      association with proteins and inorganic polyphosphate. It has been proposed that
      PHB can mediate ion transport across lipid bilayer membranes. We investigated the
      ability of PHB to interact with living cells and isolated mitochondria and the
      effects of these interactions on membrane ion transport. We performed experiments
      using a fluorescein derivative of PHB (fluo-PHB). We found that fluo-PHB
      preferentially accumulated inside the mitochondria of HeLa cells. Accumulation of
      fluo-PHB induced mitochondrial membrane depolarization. This membrane
      depolarization was significantly delayed by the inhibitor of the mitochondrial
      permeability transition pore - Cyclosporin A. Further experiments using intact
      cells as well as isolated mitochondria confirmed that the effects of PHB directly
      linked to its ability to facilitate ion transport, including calcium, across the
      membranes. We conclude that PHB demonstrates ionophoretic properties in
      biological membranes and this effect is most profound in mitochondria due to the
      selective accumulation of the polymer in this organelle. 

PMID- 24086640
TI  - Ozone exposure of a weed community produces adaptive changes in seed populations
      of Spergula arvensis.
AB  - Tropospheric ozone is one of the major drivers of global change. This stress
      factor alters plant growth and development. Ozone could act as a selection
      pressure on species communities composition, but also on population genetic
      background, thus affecting life history traits. Our objective was to evaluate the
      consequences of prolonged ozone exposure of a weed community on phenotypic traits
      of Spergulaarvensis linked to persistence. Specifically, we predicted that the
      selection pressure exerted by high ozone concentrations as well as the
      concomitant changes in the weed community would drive population adaptive changes
      which will be reflected on seed germination, dormancy and longevity. In order to
      test seed viability and dormancy level, we conducted germination experiments for
      which we used seeds produced by S. arvensis plants grown within a weed community
      exposed to three ozone treatments during four years (0, 90 and 120 ppb). We also
      performed a soil seed bank experiment to test seed longevity with seeds coming
      from both the four-year ozone exposure experiment and from a short-term treatment
      conducted at ambient and added ozone concentrations. We found that prolonged
      ozone exposure produced changes in seed germination, dormancy and longevity,
      resulting in three S. arvensis populations. Seeds from the 90 ppb ozone selection
      treatment had the highest level of germination when stored at 75% RH and 25 
      degrees C and then scarified. These seeds showed the lowest dormancy level when
      being subjected to 5 oC/5% RH and 25 oC/75% followed by 5% RH storage conditions.
      Furthermore, ozone exposure increased seed persistence in the soil through a
      maternal effect. Given that tropospheric ozone is an important pollutant in rural
      areas, changes in seed traits due to ozone exposure could increase weed
      persistence in fields, thus affecting weed-crop interactions, which could
      ultimately reduce crop production. 

PMID- 24086639
TI  - MicroRNA-150 expression induces myeloid differentiation of human acute leukemia
      cells and normal hematopoietic progenitors.
AB  - In acute myeloid leukemia (AML) and blast crisis (BC) chronic myeloid leukemia
      (CML) normal differentiation is impaired. Differentiation of immature
      stem/progenitor cells is critical for normal blood cell function. MicroRNAs
      (miRNAs or miRs) are small non-coding RNAs that interfere with gene expression by
      degrading messenger RNAs (mRNAs) or blocking protein translation. Aberrant miRNA
      expression is a feature of leukemia and miRNAs also play a significant role in
      normal hematopoiesis and differentiation. We have identified miRNAs
      differentially expressed in AML and BC CML and identified a new role for miR-150
      in myeloid differentiation. Expression of miR-150 is low or absent in BC CML and
      AML patient samples and cell lines. We have found that expression of miR-150 in
      AML cell lines, CD34+ progenitor cells from healthy individuals, and primary BC
      CML and AML patient samples at levels similar to miR-150 expression in normal
      bone marrow promotes myeloid differentiation of these cells. MYB is a direct
      target of miR-150, and we have identified that the observed phenotype is
      partially mediated by MYB. In AML cell lines, differentiation of miR-150
      expressing cells occurs independently of retinoic acid receptor alpha (RARA)
      signaling. High-throughput gene expression profiling (GEP) studies of the AML
      cell lines HL60, PL21, and THP-1 suggest that activation of CEPBA, CEBPE, and
      cytokines associated with myeloid differentiation in miR-150 expressing cells as
      compared to control cells contributes to myeloid differentiation. These data
      suggest that miR-150 promotes myeloid differentiation, a previously
      uncharacterized role for this miRNA, and that absent or low miR-150 expression
      contributes to blocked myeloid differentiation in acute leukemia cells. 

PMID- 24086641
TI  - Population sex ratios: another consideration in the reintroduction -
      reinforcement debate?
AB  - Reintroduction or reinforcement (RorR) of wild populations is a common
      conservation strategy. Many conservation projects involve the release of
      individuals of poorly studied species. This may lead to inefficient results or
      negative impacts on the conservation efforts. Here, we provide new insights into
      the conservation implications and potential consequences of a skew in the sex
      ratio of released birds and of the number of birds supplemented for the
      demography of a long-lived dimorphic bird species, the Andean condor
      (Vulturgryphus). We demonstrate that a RorR conservation program may be less
      effective in conserving a species if the sex ratios of the releases and the
      recipient populations are not considered. We also show that releases can reduce
      population declines but only if carried out over long periods (i.e., several
      decades). This can mean high costs for release programs and the added challenge
      of maintaining programs over time. If RorR programs are to be implemented,
      bearing in mind the importance of properly assessing their effectiveness, we urge
      conservation researchers and managers to consider the implications of sex ratio
      biases for wild populations, and particularly for dimorphic species with sexually
      despotic behaviour. 

PMID- 24086642
TI  - Environmental determinants of woody plant diversity at a regional scale in China.
AB  - Understanding what drives the geographic variation of species richness across the
      globe is a fundamental goal of ecology and biogeography. Environmental variables
      have been considered as drivers of global diversity patterns but there is no
      consensus among ecologists on what environmental variables are primary drivers of
      the geographic variation of species richness. Here, I examine the relationship of
      woody plant species richness at a regional scale in China with sixteen
      environmental variables representing energy availability, water availability,
      energy-water balance, seasonality, and habitat heterogeneity. I found that
      temperature seasonality is the best predictor of woody species richness in China.
      Other important environmental variables include annual precipitation, mean
      temperature of the coldest month, and potential evapotranspiration. The best
      model explains 85% of the variation in woody plant species richness at the
      regional scale in China. 

PMID- 24086644
TI  - Tissue microarray immunohistochemical detection of brachyury is not a prognostic
      indicator in chordoma.
AB  - Brachyury is a marker for notochord-derived tissues and neoplasms, such as
      chordoma. However, the prognostic relevance of brachyury expression in chordoma
      is still unknown. The improvement of tissue microarray technology has provided
      the opportunity to perform analyses of tumor tissues on a large scale in a
      uniform and consistent manner. This study was designed with the use of tissue
      microarray to determine the expression of brachyury. Brachyury expression in
      chordoma tissues from 78 chordoma patients was analyzed by immunohistochemical
      staining of tissue microarray. The clinicopathologic parameters, including
      gender, age, location of tumor and metastatic status were evaluated. Fifty-nine
      of 78 (75.64%) tumors showed nuclear staining for brachyury, and among them, 29
      tumors (49.15%) showed 1+ (<30% positive cells) staining, 15 tumors (25.42%) had
      2+ (31% to 60% positive cells) staining, and 15 tumors (25.42%) demonstrated 3+
      (61% to 100% positive cells) staining. Brachyury nuclear staining was detected
      more frequently in sacral chordomas than in chordomas of the mobile spine.
      However, there was no significant relationship between brachyury expression and
      other clinical variables. By Kaplan-Meier analysis, brachyury expression failed
      to produce any significant relationship with the overall survival rate. In
      conclusion, brachyury expression is not a prognostic indicator in chordoma. 

PMID- 24086643
TI  - Platelet activating factor-induced ceramide micro-domains drive endothelial NOS
      activation and contribute to barrier dysfunction.
AB  - The spatial and functional relationship between platelet activating factor
      receptor (PAF-R) and nitric oxide synthase (eNOS) in the lateral plane of the
      endothelial plasma membrane is poorly characterized. In this study, we used
      intact mouse pulmonary endothelial cells (ECs) as well as endothelial plasma
      membrane patches and subcellular fractions to define a new microdomain of
      plasmalemma proper where the two proteins colocalize and to demonstrate how PAF
      mediated nitric oxide (NO) production fine-tunes ECs function as gatekeepers of
      vascular permeability. Using fluorescence microscopy and immunogold labeling
      electron microscopy (EM) on membrane patches we demonstrate that PAF-R is
      organized as clusters and colocalizes with a subcellular pool of eNOS, outside
      recognizable vesicular profiles. Moreover, PAF-induced acid sphingomyelinase
      activation generates a ceramide-based microdomain on the external leaflet of
      plasma membrane, inside of which a signalosome containing eNOS shapes PAF
      stimulated NO production. Real-time measurements of NO after PAF-R ligation
      indicated a rapid (5 to 15 min) increase in NO production followed by a > 45 min
      period of reduction to basal levels. Moreover, at the level of this new
      microdomain, PAF induces a dynamic phosphorylation/dephosphorylation of Ser, Thr
      and Tyr residues of eNOS that correlates with NO production. Altogether, our
      findings establish the existence of a functional partnership PAF-R/eNOS on EC
      plasma membrane, at the level of PAF-induced ceramide plasma membrane
      microdomains, outside recognized vesicular profiles. 

PMID- 24086645
TI  - Induction of cytopathogenicity in human glioblastoma cells by chikungunya virus.
AB  - Chikungunya virus (CHIKV), an arthritogenic old-world alphavirus, has been
      implicated in the central nervous system (CNS) infection in infants and elderly
      patients. Astrocytes are the major immune cells of the brain parenchyma that
      mediate inflammation. In the present study we found that a local isolate of CHIKV
      infect and activate U-87 MG cells, a glioblastoma cell line of human astrocyte
      origin. The infection kinetics were similar in infected U-87 MG cells and the
      human embryo kidney (HEK293) cells as indicated by immunofluorescence and plaque
      assays, 24h post-infection (p.i.). In infected U-87 MG cells, apoptosis was
      detectable from 48h p.i. evidenced by DNA fragmentation, PARP cleavage, loss of
      mitochondrial membrane potential, nuclear condensation and visible cytopathic
      effects in a dose and time-dependent manner. XBP1 mRNA splicing and eIF2alpha
      phosphorylation studies indicated the occurrence of endoplasmic reticulum stress
      in infected cells. In U-87 MG cells stably expressing a green fluorescent protein
      tagged light chain-3 (GFP-LC3) protein, CHIKV infection showed increased
      autophagy response. The infection led to an enhanced expression of the mRNA
      transcripts of the pro-inflammatory cytokines IL-1beta, TNF-alpha, IL-6 and CXCL9
      within 24h p.i. Significant up-regulation of the proteins of RIG-I like receptor
      (RLR) pathway, such as RIG-I and TRAF-6, was observed indicating the activation
      of the cytoplasmic-cellular innate immune response. The overall results show that
      the U-87 MG cell line is a potential in vitro model for in depth study of these
      molecular pathways in response to CHIKV infection. The responses in these cells
      of CNS origin, which are inherently defective in Type I interferon response,
      could be analogous to that occurring in infants and very old patients who also
      have a compromised interferon-response. The results also point to the intriguing
      possibility of using this virus for studies to develop oncolytic virus therapy
      approaches against glioblastoma, a highly aggressive malignancy. 

PMID- 24086646
TI  - Impact of young age on the prognosis for oral cancer: a population-based study in
      Taiwan.
AB  - BACKGROUND: Oral cancer leads to a considerable use of health care resources.
      Wide resection of the tumor and reconstruction with a pedicle flap/ free flap is
      widely used. This study was conducted to investigate if young age at the time of
      diagnosis of oral cancer requiring this treatment confers a worse prognosis.
      METHODS: A total of 2339 patients who underwent resections for oral cancer from
      2004 to 2005 were identified from The Taiwan National Health Insurance Research
      Database. Survival analysis, Cox proportional regression model, propensity
      scores, and sensitivity test were used to evaluate the association between 5-year
      survival rates and age. RESULTS: In the Cox proportional regression model, the
      older age group (>65 years) had the worst survival rate (hazard ratio [HR], 1.80;
      95% confidence interval [CI], 1.45-2.22; P<0.001). When analyzed using the
      propensity scores, the adjusted 5-year survival rates were also poorer for oral
      cancer patients with older age (>65 years), compared to those with younger age
      (<45 years) (P<0.001). In sensitivity test, the adjusted hazard ratio remained no
      statistically elevated in the younger age group (<45 years). CONCLUSIONS: For
      those oral cancer patients who underwent wide excision and reconstruction, young
      age did not confer a worse prognosis using a Cox proportional regression model,
      propensity scores or sensitivity test. Young oral cancer patients may be treated
      using general guidelines and do not require more aggressive treatment.

PMID- 24086647
TI  - Soil nutrient assessment for urban ecosystems in Hubei, China.
AB  - Recent urban landscape vegetation surveys conducted in many cities in China
      identified numerous plant nutrient deficiencies, especially in newly developed
      cities. Soil nutrients and soil nutrient management in the cities of Hubei
      province have not received adequate attention to date. The aims of this study
      were to characterize the available nutrients of urban soils from nine cities in
      Hubei province, China, and to assess how soil nutrient status is related to land
      use type and topography. Soil nutrients were measured in 405 sites from 1,215
      soil samples collected from four land use types (park, institutional [including
      government building grounds, municipal party grounds, university grounds, and
      garden city institutes], residential, and roadside verges) and three topographies
      (mountainous [142-425 m a.s.l], hilly [66-112 m a.s.l], and plain [26-30 m
      a.s.l]). Chemical analyses showed that urban soils in Hubei had high pH and lower
      soil organic matter, available nitrogen (N), available phosphorus (P), and
      available boron (B) concentrations than natural soils. Nutrient concentrations
      were significantly different among land use types, with the roadside and
      residential areas having greater concentrations of calcium (Ca), sulfur (S),
      copper (Cu), manganese (Mn), and zinc (Zn) that were not deficient against the
      recommended ranges. Topographic comparisons showed statistically significant
      effects for 8 of the 11 chemical variables (p < 0.05). Concentrations of N, Ca,
      Mg, S, Cu, and Mn in plain cities were greater than those in mountainous cities
      and show a negative correlation with city elevation. These results provide data
      on urban soils characteristics in land use types and topography, and deliver
      significant information for city planners and policy makers. 

PMID- 24086648
TI  - Can convict Cichlids (Amatitlania siquia) socially learn the degree of predation
      risk associated with novel visual cues in their environment?
AB  - For many animals, the ability to distinguish cues indicative of predation risk
      from cues unrelated to predation risk is not entirely innate, but rather is
      learned and improved with experience. Two pathways to such learning are possible.
      First, an animal could initially express antipredator behaviour toward a wide
      range of cues and subsequently learn which of those cues are non-threatening.
      Alternatively, it could initially express no antipredator behaviour toward a wide
      range of cues and subsequently learn which of them are threatening. While the
      learned recognition of threatening cues may occur either through personal
      interaction with a cue (asocial learning) or through observation of the behaviour
      of social companions toward a cue (social learning), the learned recognition of
      non-threatening cues seems to occur exclusively through habituation, a form of
      asocial learning. Here, we tested whether convict cichlid fish
      (Amatitlaniasiquia) can socially learn to recognize visual cues in their
      environment as either threatening or non-threatening. We exposed juvenile convict
      cichlids simultaneously to a novel visual cue and one of three (visual) social
      cues: a social cue indicative of non-risk (the sight of conspecifics that had
      previously been habituated to the novel cue), a social cue indicative of
      predation risk (the sight of conspecifics trained to fear the novel cue), or a
      control treatment with no social cue. The subsequent response of focal fish, when
      presented with the novel cue alone, was not influenced by the social cue that
      they had previously witnessed. We therefore did not find evidence that convict
      cichlids in our study could use social learning to recognize novel visual cues as
      either threatening or non-threatening. We consider alternative explanations for
      our findings. 

PMID- 24086649
TI  - Overexpression of TROP2 predicts poor prognosis of patients with cervical cancer
      and promotes the proliferation and invasion of cervical cancer cells by
      regulating ERK signaling pathway.
AB  - Overwhelming evidence has demonstrated that the aberrant expression of the human
      trophoblast cell-surface antigen (TROP2) was associated with tumor aggressiveness
      and poor prognosis in a variety of human cancers, however the roles of TROP2 in
      cervical cancer have not been investigated. The purpose of our study was to
      elucidate the prognostic significance of TROP2 expression in patients with
      cervical cancer and determine its effect on tumor progression.
      Immunohistochemistry assay showed that 88.7% (94/106 cases) of cervical cancer
      specimens were positively stained with TROP2, and the overexpression of TROP2 was
      closely related with FIGO stage, histological grades, lymphatic metastasis,
      invasive interstitial depth and high expression of Ki-67. Patients with TROP2
      positive staining exhibited a significantly decreased overall survival and
      progression free survival; it was also an independent predictor for prognosis
      according to multivariate analysis. Moreover, down-regulation of TROP2 mediated
      by siRNA in Siha and CaSki cells resulted in a strong inhibition of proliferation
      and invasion, TROP2 abrogation also elevated the apoptotic ratio and caused G1
      arrest. Conversely, enforced expression of TROP2 in HeLa and C33A cells
      remarkably promoted cell growth, migration and invasion. In addition, the
      tumorigenic function of TROP2 was associated with the increased expressions of
      cyclin D1, cyclin E, CDK2 and CDK4 but reduced expression of p27 and E-cadherin
      via the activation of Erk1/2 signaling pathway. Furthermore, the inhibition of
      TROP2 expression in cervical cancer cell lines enhances sensitivity to cisplatin.
      The present study suggest that overexpression of TROP2 may play crucial roles in
      the development and pathogenesis of human cervical cancer, therefore, TROP2 may
      represent a prospective prognostic indicator and a potential therapeutic target
      of cervical cancer. 

PMID- 24086650
TI  - Improvement of neuromuscular synaptic phenotypes without enhanced survival and
      motor function in severe spinal muscular atrophy mice selectively rescued in
      motor neurons.
AB  - In the inherited childhood neuromuscular disease spinal muscular atrophy (SMA),
      lower motor neuron death and severe muscle weakness result from the reduction of
      the ubiquitously expressed protein survival of motor neuron (SMN). Although SMA
      mice recapitulate many features of the human disease, it has remained unclear if
      their short lifespan and motor weakness are primarily due to cell-autonomous
      defects in motor neurons. Using Hb9(Cre) as a driver, we selectively raised SMN
      expression in motor neurons in conditional SMADelta7 mice. Unlike a previous
      study that used choline acetyltransferase (ChAT(Cre+) ) as a driver on the same
      mice, and another report that used Hb9(Cre) as a driver on a different line of
      conditional SMA mice, we found no improvement in survival, weight, motor behavior
      and presynaptic neurofilament accumulation. However, like in ChAT(Cre+) mice, we
      detected rescue of endplate size and mitigation of neuromuscular junction (NMJ)
      denervation status. The rescue of endplate size occurred in the absence of an
      increase in myofiber size, suggesting endplate size is determined by the motor
      neuron in these animals. Real time-PCR showed that the expression of spinal cord
      SMN transcript was sharply reduced in Hb9(Cre+) SMA mice relative to ChAT(Cre+)
      SMA mice. This suggests that our lack of overall phenotypic improvement is most
      likely due to an unexpectedly poor recombination efficiency driven by Hb9(Cre) .
      Nonetheless, the low levels of SMN were sufficient to rescue two NMJ structural
      parameters indicating that these motor neuron cell autonomous phenotypes are very
      sensitive to changes in motoneuronal SMN levels. Our results directly suggest
      that even those therapeutic interventions with very modest effects in raising SMN
      in motor neurons may provide mitigation of neuromuscular phenotypes in SMA
      patients. 

PMID- 24086651
TI  - Cell wall degrading enzyme induced rice innate immune responses are suppressed by
      the type 3 secretion system effectors XopN, XopQ, XopX and XopZ of Xanthomonas
      oryzae pv. oryzae.
AB  - Innate immune responses are induced in plants and animals through perception of
      Damage Associated Molecular Patterns. These immune responses are suppressed by
      pathogens during infection. A number of studies have focussed on identifying
      functions of plant pathogenic bacteria that are involved in suppression of
      Pathogen Associated Molecular Pattern induced immune responses. In comparison,
      there is very little information on functions used by plant pathogens to suppress
      Damage Associated Molecular Pattern induced immune responses. Xanthomonasoryzae
      pv. oryzae, a gram negative bacterial pathogen of rice, secretes hydrolytic
      enzymes such as LipA (Lipase/Esterase) that damage rice cell walls and induce
      innate immune responses. Here, we show that Agrobacterium mediated transient
      transfer of the gene for XopN, a X. oryzae pv. oryzae type 3 secretion (T3S)
      system effector, results in suppression of rice innate immune responses induced
      by LipA. A xopN (-) mutant of X. oryzae pv. oryzae retains the ability to
      suppress these innate immune responses indicating the presence of other
      functionally redundant proteins. In transient transfer assays, we have assessed
      the ability of 15 other X. oryzae pv. oryzae T3S secreted effectors to suppress
      rice innate immune responses. Amongst these proteins, XopQ, XopX and XopZ are
      suppressors of LipA induced innate immune responses. A mutation in any one of the
      xopN, xopQ, xopX or xopZ genes causes partial virulence deficiency while a xopN (
      ) xopX (-) double mutant exhibits a greater virulence deficiency. A xopN (-) xopQ
      (-) xopX (-) xopZ (-) quadruple mutant of X. oryzae pv. oryzae induces callose
      deposition, an innate immune response, similar to a X. oryzae pv. oryzae T3S(-)
      mutant in rice leaves. Overall, these results indicate that multiple T3S secreted
      proteins of X. oryzae pv. oryzae can suppress cell wall damage induced rice
      innate immune responses. 

PMID- 24086652
TI  - The broken MLL gene is frequently located outside the inherent chromosome
      territory in human lymphoid cells treated with DNA topoisomerase II poison
      etoposide.
AB  - The mixed lineage leukaemia (MLL) gene is frequently rearranged in secondary
      leukaemias, in which it could fuse to a variety of different partners. Breakage
      in the MLL gene preferentially occurs within a ~8 kb region that possesses a
      strong DNA topoisomerase II cleavage site. It has been proposed that DNA
      topoisomerase II-mediated DNA cleavage within this and other regions triggers
      translocations that occur due to incorrect joining of broken DNA ends. To further
      clarify a possible mechanism for MLL rearrangements, we analysed the frequency of
      MLL cleavage in cells exposed to etoposide, a DNA topoisomerase II poison
      commonly used as an anticancer drug, and positioning of the broken 3'-end of the
      MLL gene in respect to inherent chromosomal territories. It was demonstrated that
      exposure of human Jurkat cells to etoposide resulted in frequent cleavage of MLL
      genes. Using MLL-specific break-apart probes we visualised cleaved MLL genes in
      ~17% of nuclei. Using confocal microscopy and 3D modelling, we demonstrated that
      in cells treated with etoposide and cultivated for 1 h under normal conditions,
      ~9% of the broken MLL alleles were present outside the chromosome 11 territory,
      whereas in both control cells and cells inspected immediately after etoposide
      treatment, virtually all MLL alleles were present within the chromosomal
      territory. The data are discussed in the framework of the "breakage first" model
      of juxtaposing translocation partners. We propose that in the course of repairing
      DNA topoisomerase II-mediated DNA lesions (removal of stalled DNA topoisomerase
      II complexes and non-homologous end joining), DNA ends acquire additional
      mobility, which allows the meeting and incorrect joining of translocation
      partners. 

PMID- 24086654
TI  - Musical experience, auditory perception and reading-related skills in children.
AB  - BACKGROUND: The relationships between auditory processing and reading-related
      skills remain poorly understood despite intensive research. Here we focus on the
      potential role of musical experience as a confounding factor. Specifically we ask
      whether the pattern of correlations between auditory and reading related skills
      differ between children with different amounts of musical experience.
      METHODOLOGY/PRINCIPAL FINDINGS: Third grade children with various degrees of
      musical experience were tested on a battery of auditory processing and reading
      related tasks. Very poor auditory thresholds and poor memory skills were abundant
      only among children with no musical education. In this population, indices of
      auditory processing (frequency and interval discrimination thresholds) were
      significantly correlated with and accounted for up to 13% of the variance in
      reading related skills. Among children with more than one year of musical
      training, auditory processing indices were better, yet reading related skills
      were not correlated with them. A potential interpretation for the reduction in
      the correlations might be that auditory and reading-related skills improve at
      different rates as a function of musical training. CONCLUSIONS/SIGNIFICANCE:
      Participants' previous musical training, which is typically ignored in studies
      assessing the relations between auditory and reading related skills, should be
      considered. Very poor auditory and memory skills are rare among children with
      even a short period of musical training, suggesting musical training could have
      an impact on both. The lack of correlation in the musically trained population
      suggests that a short period of musical training does not enhance reading related
      skills of individuals with within-normal auditory processing skills. Further
      studies are required to determine whether the associations between musical
      training, auditory processing and memory are indeed causal or whether children
      with poor auditory and memory skills are less likely to study music and if so,
      why this is the case.

PMID- 24086653
TI  - Pro-inflammatory cytokine induction of 11beta-hydroxysteroid dehydrogenase type 1
      in A549 cells requires phosphorylation of C/EBPbeta at Thr235.
AB  - 11beta-hydroxysteroid dehydrogenase type 1 (11beta-HSD1) converts inert
      glucocorticoids into active forms, thereby increasing intracellular
      glucocorticoid levels, important to restrain acute inflammation. 11beta-HSD1 is
      induced by pro-inflammatory cytokines in a variety of cells. Here, we show 11beta
      HSD1 expression in human A549 epithelial cells is increased by pro-inflammatory
      cytokines (IL-1alpha/TNFalpha) via the P2 promoter of the HSD11B1 gene.
      Inhibition of p38 MAPK attenuated the pro-inflammatory cytokine induction of mRNA
      encoding 11beta-HSD1 as well as that encoding C/EBPbeta. IL-1alpha/TNFalpha
      induced phosphorylation of C/EBPbeta at Thr235 was also attenuated by p38 MAPK
      inhibition suggesting involvement of a p38 MAPK-C/EBPbeta pathway. siRNA-mediated
      knock-down of C/EBPbeta and NF-kappaB/RelA implicated both transcription factors
      in the IL-1alpha/TNFalpha induction of HSD11B1 mRNA. Transient transfections of
      HSD11B1 promoter-reporter constructs identified the proximal region of the P2
      promoter of HSD11B1 as essential for this induction. IL-1alpha increased binding
      of C/EBPbeta to the HSD11B1 P2 promoter, but this was not observed for NF
      kappaB/RelA, suggesting indirect regulation by NF-kappaB/RelA. Ectopic expression
      of mutant chicken C/EBPbeta constructs unable to undergo phosphorylation at the
      threonine equivalent to Thr235 attenuated the IL-1alpha-induction of HSD11B1,
      whereas mimicking constitutive phosphorylation of Thr235 (by mutation to
      aspartate) increased basal expression of HSD11B1 mRNA without affecting IL-1alpha
      induced levels. These data clearly demonstrate a role for both C/EBPbeta and NF
      kappaB/RelA in the pro-inflammatory cytokine induction of HSD11B1 in human
      epithelial cells and show that p38 MAPK-induced phosphorylation of C/EBPbeta at
      Thr235 is critical in this. 

PMID- 24086655
TI  - Psychological and physiological responses following repeated peer death.
AB  - OBJECTIVE: Undergraduates at a university in the United States were exposed -
      directly and indirectly - to 14 peer deaths during one academic year. We examined
      how individual and social factors were associated with psychological (e.g.,
      anxiety, depression, somatization) and physiological (i.e., cortisol) distress
      responses following this unexpected and repeated experience with loss. METHOD:
      Two to three months after the final peer death, respondents (N = 122, 61% female,
      18-23 years, M = 20.13, SD = 1.14) reported prior adverse experiences, degree of
      closeness with the deceased, acute responses to the peer deaths, ongoing distress
      responses, social support, support seeking, and media viewing. A subset (n = 24)
      returned hair samples for evaluation of cortisol responses during the previous 3
      months. RESULTS: Ongoing psychological distress was associated with a) prior
      interpersonal trauma, b) fewer social supports, and c) media exposure to news of
      the deaths (p's<.05). Participants who had no prior bereavements showed, on
      average, high cortisol (>25 p/mg) compared to individuals with one or two prior
      bereavement experiences (who were, on average, within the normal range, 10 to 25
      p/mg) (p<.05). Only 8% of the sample utilized available university psychological
      or physical health resources and support groups. CONCLUSIONS: Limited research
      has examined the psychological and physiological impact of exposure to chronic,
      repeated peer loss, despite the fact that there are groups of individuals (e.g.,
      police, military soldiers) that routinely face such exposures. Prior adversity
      appears to play a role in shaping psychological and physiological responses to
      repeated loss. This topic warrants further research given the health implications
      of repeated loss for individuals in high-risk occupations and university
      settings.

PMID- 24086656
TI  - microRNA-22 promotes heart failure through coordinate suppression of PPAR/ERR
      nuclear hormone receptor transcription.
AB  - Increasing evidence suggests that microRNAs are intimately involved in the
      pathophysiology of heart failure. MicroRNA-22 (miR-22) is a muscle-enriched miRNA
      required for optimum cardiac gene transcription and adaptation to hemodynamic
      stress by pressure overload in mice. Recent evidence also suggests that miR-22
      induces hypertrophic growth and it is oftentimes upregulated in end stage heart
      failure. However the scope of mRNA targets and networks of miR-22 in the heart
      failure remained unclear. We analyzed transgenic mice with enhanced levels of miR
      22 expression in adult cardiomyocytes to identify important pathophysiologic
      targets of miR-22. Our data shows that forced expression of miR-22 induces a pro
      hypertrophic gene expression program, and it elicits contractile dysfunction
      leading to cardiac dilation and heart failure. Increased expression of miR-22
      impairs the Ca(2+) transient, Ca(2+) loading into the sarcoplasmic reticulum plus
      it interferes with transcription of estrogen related receptor (ERR) and PPAR
      downstream genes. Mechanistically, miR-22 postranscriptionally inhibits
      peroxisome proliferator-activated receptor gamma coactivator 1 alpha (PGC
      1alpha), PPARalpha and sirtuin 1 (SIRT1) expression via a synergistic circuit,
      which may account for deleterious actions of unchecked miR-22 expression on the
      heart. 

PMID- 24086657
TI  - Gfi1 and gfi1b repress rag transcription in plasmacytoid dendritic cells in
      vitro.
AB  - Growth factor independence genes (Gfi1 and Gfi1b) repress recombination
      activating genes (Rag) transcription in developing B lymphocytes. Because all
      blood lineages originate from hematopoietic stem cells (HSCs) and different
      lineage progenitors have been shown to share transcription factor networks prior
      to cell fate commitment, we hypothesized that GFI family proteins may also play a
      role in repressing Rag transcription or a global lymphoid transcriptional program
      in other blood lineages. We tested the level of Rag transcription in various
      blood cells when Gfi1 and Gfi1b were deleted, and observed an upregulation of Rag
      expression in plasmacytoid dendritic cells (pDCs). Using microarray analysis, we
      observed that Gfi1 and Gfi1b do not regulate a lymphoid or pDC-specific
      transcriptional program. This study establishes a role for Gfi1 and Gfi1b in Rag
      regulation in a non-B lineage cell type. 

PMID- 24086658
TI  - The acute side effects of bright light therapy: a placebo-controlled
      investigation.
AB  - Despite the emergence of numerous clinical and non-clinical applications of
      bright light therapy (LT) in recent decades, the prevalence and severity of LT
      side effects have not yet been fully explicated. A few adverse LT effects
      headache, eye strain, irritability, and nausea-have been consistently reported
      among depressed individuals and other psychiatric cohorts, but there exists
      little published evidence regarding LT side effects in non-clinical populations,
      who often undergo LT treatment of considerably briefer duration. Accordingly, in
      the present study we examined, in a randomized sample of healthy young adults,
      the acute side effects of exposure to a single 30-minute session of bright white
      light (10,000 lux) versus dim red light (< 500 lux). Across a broad range of
      potential side effects, repeated-measures analyses of variance revealed no
      significant group-by-time (Pre, Post) interactions. In other words, bright light
      exposure was not associated with a significantly higher incidence of any reported
      side effect than was the placebo control condition. Nevertheless, small but
      statistically significant increases in both eye strain and blurred vision were
      observed among both the LT and control groups. Overall, these results suggest
      that the relatively common occurrence of adverse side effects observed in the
      extant LT literature may not fully extend to non-clinical populations, especially
      for healthy young adults undergoing LT for a brief duration. 

PMID- 24086659
TI  - Systemic delivery of shRNA by AAV9 provides highly efficient knockdown of
      ubiquitously expressed GFP in mouse heart, but not liver.
AB  - AAV9 is a powerful gene delivery vehicle capable of providing long-term gene
      expression in a variety of cell types, particularly cardiomyocytes. The use of
      AAV-delivery for RNA interference is an intense area of research, but a
      comprehensive analysis of knockdown in cardiac and liver tissues after systemic
      delivery of AAV9 has yet to be reported. We sought to address this question by
      using AAV9 to deliver a short-hairpin RNA targeting the enhanced green
      fluorescent protein (GFP) in transgenic mice that constitutively overexpress GFP
      in all tissues. The expression cassette was initially tested in vitro and we
      demonstrated a 61% reduction in mRNA and a 90% reduction in GFP protein in dual
      transfected 293 cells. Next, the expression cassette was packaged as single
      stranded genomes in AAV9 capsids to test cardiac GFP knockdown with several doses
      ranging from 1.8*10(10) to 1.8*10(11) viral genomes per mouse and a dose
      dependent response was obtained. We then analyzed GFP expression in both heart
      and liver after delivery of 4.4*10(11) viral genomes per mouse. We found that
      while cardiac knockdown was highly efficient, with a 77% reduction in GFP mRNA
      and a 71% reduction in protein versus control-treated mice, there was no change
      in liver expression. This was despite a 4.5-fold greater number of viral genomes
      in the liver than in the heart. This study demonstrates that single-stranded AAV9
      vectors expressing shRNA can be used to achieve highly efficient cardiac
      selective knockdown of GFP expression that is sustained for at least 7 weeks
      after the systemic injection of 8 day old mice, with no change in liver
      expression and no evidence of liver damage despite high viral genome presence in
      the liver. 

PMID- 24086660
TI  - Highly efficient retrograde gene transfer into motor neurons by a lentiviral
      vector pseudotyped with fusion glycoprotein.
AB  - The development of gene therapy techniques to introduce transgenes that promote
      neuronal survival and protection provides effective therapeutic approaches for
      neurological and neurodegenerative diseases. Intramuscular injection of
      adenoviral and adeno-associated viral vectors, as well as lentiviral vectors
      pseudotyped with rabies virus glycoprotein (RV-G), permits gene delivery into
      motor neurons in animal models for motor neuron diseases. Recently, we developed
      a vector with highly efficient retrograde gene transfer (HiRet) by pseudotyping a
      human immunodeficiency virus type 1 (HIV-1)-based vector with fusion glycoprotein
      B type (FuG-B) or a variant of FuG-B (FuG-B2), in which the cytoplasmic domain of
      RV-G was replaced by the corresponding part of vesicular stomatitis virus
      glycoprotein (VSV-G). We have also developed another vector showing neuron
      specific retrograde gene transfer (NeuRet) with fusion glycoprotein C type, in
      which the short C-terminal segment of the extracellular domain and
      transmembrane/cytoplasmic domains of RV-G was substituted with the corresponding
      regions of VSV-G. These two vectors afford the high efficiency of retrograde gene
      transfer into different neuronal populations in the brain. Here we investigated
      the efficiency of the HiRet (with FuG-B2) and NeuRet vectors for retrograde gene
      transfer into motor neurons in the spinal cord and hindbrain in mice after
      intramuscular injection and compared it with the efficiency of the RV-G
      pseudotype of the HIV-1-based vector. The main highlight of our results is that
      the HiRet vector shows the most efficient retrograde gene transfer into both
      spinal cord and hindbrain motor neurons, offering its promising use as a gene
      therapeutic approach for the treatment of motor neuron diseases. 

PMID- 24086661
TI  - Sequence polymorphism and expression variability of Crassostrea gigas immune
      related genes discriminate two oyster lines contrasted in term of resistance to
      summer mortalities.
AB  - Summer mortalities of Crassostreagigas are a major concern in oyster aquaculture.
      They are the result of a complex interaction between the host, pathogens and
      environmental factors. Oyster genetics have been identified as an essential
      determinant of oyster susceptibility to summer mortalities. As the capability of
      oysters to circumvent diseases depends in part on their immune defenses, we aimed
      to analyze the gene expression and sequence polymorphism of 42 immune related
      genes in two oyster lines selected for their "High" (H) and "Low" (L) survival to
      summer mortalities. Results showed that the variability of gene expression and
      the sequence polymorphism acting on particular genes could enable the
      discrimination between H and L oyster lines. Besides, a higher sequence
      polymorphism was observed on the L line affecting 11 of the 42 analyzed genes. By
      analyzing gene expression, sequence polymorphism and gene copy number of two
      antimicrobial peptide families (Cg-Defs and Cg-Prp), and an antimicrobial protein
      (Cg-BPI) on individual oysters, we showed that gene expression and/or sequence
      polymorphism could also discriminate H and L oyster lines. Finally, we observed a
      positive correlation between the gene expression and the gene copy number of
      antimicrobials and that sequence polymorphism could be encoded in the genome.
      Overall, this study gives new insights in the relationship between oyster
      immunity and divergent phenotypes, and discusses the potential implication of
      antimicrobial diversity in oyster survival to summer mortalities. 

PMID- 24086662
TI  - Thoracic tumor volume delineation in 4D-PET/CT by low dose interpolated CT for
      attenuation correction.
AB  - PURPOSE: 4D-PET/CT imaging is an excellent solution for reducing the breathing
      induced effects in both CT and PET images. In 4D-PET/CT, 4D-CT images are
      selected to match those of 4D-PET phase by phase and the corresponding phases are
      used for attenuation correction in 4D-PET. However, the high radiation dose that
      patients acquire while undergoing 4D-CT imaging for diagnostic purposes remains a
      concern. This study aims to assess low-dose interpolated CT (ICT) for PET
      attenuation correction (PETICT) in thoracic tumor volume delineation. METHODS AND
      MATERIALS: Twelve thoracic cancer patients (10 esophageal and 2 lung cancer
      cases) were recruited. All patients underwent 4D-PET/CT scans. The optical flow
      method based on image intensity gradient was applied to calculate the motion
      displacement in three dimensions for each voxel on two original extreme CT phases
      in the respiratory cycle, end-inspiration and end-expiration. The interpolated
      CTs were generated from two phases of the original 4D-CT using motion
      displacement. RESULTS: Tumor motion due to respiration was estimated in the
      anterior-posterior dimension, the lateral dimension and the superior-inferior
      dimension by the optical flow method. The PETICT and ICT (4D-PET ICT/ICT) matched
      each other spatially in all the phases. The distortion of tumor shape and size
      resulting from respiratory motion artifacts were not observed in 4D-PETICT. The
      tumor volume measured by 4D-PET ICT/ICT correlated to the tumor volume measured
      by 4D-PET/CT (p = 0.98). CONCLUSIONS: 4D-PETICT consistently represented the
      interpretation of FDG uptake as effectively as 4D-PET. 4D-PET ICT/ICT is a low
      dose alternative to 4D-CT and significantly improves the interpretation of PET
      and CT images, while solving the respiratory motion problem as effectively as 4D
      PET/CT.

PMID- 24086663
TI  - Pathogenicity of pandemic H1N1 influenza A virus in immunocompromised cynomolgus
      macaques.
AB  - Pandemic (H1N1) 2009 influenza virus spread throughout the world since most
      people did not have immunity against the virus. In the post pandemic phase when
      many humans might possess immunity against the pandemic virus, one of the
      concerns is infection in immunocompromised people. Therefore, we used an
      immunosuppressed macaque model to examine pathogenicity of the pandemic (H1N1)
      2009 virus under an immunocompromised condition. The virus in nasal samples of
      immunosuppressed macaques infected with the pandemic (H1N1) 2009 virus was
      detected longer after infection than was the virus in nasal samples of
      immunocompetent macaques. As expected, not only virus amounts but also virus
      propagation sites in the immunosuppressed macaques were larger than those in
      lungs of the immunocompetent macaques when they were infected with the pandemic
      virus. Immunosuppressed macaques possessed low levels of immune cells producing
      cytokines and chemokines, but levels of inflammatory cytokines/chemokine
      interleukin (IL)-6, IL-18, and monocyte chemotactic protein (MCP)-1 in lungs of
      the immunosuppressed macaques were higher than those in lungs of the
      immunocompetent macaques, though the differences were not statistically
      significant. Therefore, under an immunosuppressive condition, the pandemic
      influenza (H1N1) 2009 virus might cause more severe morbidity with high
      cytokine/chemokine production by the host innate immune system than that seen in
      macaques under the immunocompetent condition. 

PMID- 24086664
TI  - Effects of emotional contexts on cerebello-thalamo-cortical activity during
      action observation.
AB  - Several studies investigated the neural and functional mechanisms underlying
      action observation in contexts with objects. However, actions seen in everyday
      life are often embedded in emotional contexts. The neural systems integrating
      emotion cues in action observation are still poorly understood. Previous findings
      suggest that the processing of both action and emotion information recruits motor
      control areas within the cerebello-thalamo-cortical pathways. It is therefore
      hard to determine whether social emotional contexts influence action processing
      via a direct modulation of motor representations coding for the observed action
      or via the affective state and implicit motor preparedness elicited in observers
      in response to emotional contexts. Here we designed a novel fMRI task to identify
      neural networks engaged by the affective appraisal of a grasping action seen in
      two different emotional contexts, while keeping the action kinematics constant.
      Results confirmed that observing the same acts of grasping but in different
      emotional contexts modulated activity in supplementary motor area, ventrolateral
      thalamus, anterior cerebellum. Moreover, changes in functional connectivity
      between left supplementary motor area and parahippocampus in different emotional
      contexts suggested a direct neural pathway through which emotional contexts may
      drive the neural motor system. Taken together, these findings shed new light on
      the malleability of motor system as a function of emotional contexts. 

PMID- 24086666
TI  - Examining the effectiveness of discriminant function analysis and cluster
      analysis in species identification of male field crickets based on their calling
      songs.
AB  - Traditional taxonomy based on morphology has often failed in accurate species
      identification owing to the occurrence of cryptic species, which are
      reproductively isolated but morphologically identical. Molecular data have thus
      been used to complement morphology in species identification. The sexual
      advertisement calls in several groups of acoustically communicating animals are
      species-specific and can thus complement molecular data as non-invasive tools for
      identification. Several statistical tools and automated identifier algorithms
      have been used to investigate the efficiency of acoustic signals in species
      identification. Despite a plethora of such methods, there is a general lack of
      knowledge regarding the appropriate usage of these methods in specific taxa. In
      this study, we investigated the performance of two commonly used statistical
      methods, discriminant function analysis (DFA) and cluster analysis, in
      identification and classification based on acoustic signals of field cricket
      species belonging to the subfamily Gryllinae. Using a comparative approach we
      evaluated the optimal number of species and calling song characteristics for both
      the methods that lead to most accurate classification and identification. The
      accuracy of classification using DFA was high and was not affected by the number
      of taxa used. However, a constraint in using discriminant function analysis is
      the need for a priori classification of songs. Accuracy of classification using
      cluster analysis, which does not require a priori knowledge, was maximum for 6-7
      taxa and decreased significantly when more than ten taxa were analysed together.
      We also investigated the efficacy of two novel derived acoustic features in
      improving the accuracy of identification. Our results show that DFA is a reliable
      statistical tool for species identification using acoustic signals. Our results
      also show that cluster analysis of acoustic signals in crickets works effectively
      for species classification and identification. 

PMID- 24086665
TI  - Heme oxygenase-1 prevents cardiac dysfunction in streptozotocin-diabetic mice by
      reducing inflammation, oxidative stress, apoptosis and enhancing autophagy.
AB  - Heme oxygenase-1 (HO-1) has been implicated in cardiac dysfunction, oxidative
      stress, inflammation, apoptosis and autophagy associated with heart failure, and
      atherosclerosis, in addition to its recognized role in metabolic syndrome and
      diabetes. Numerous studies have presented contradictory findings about the role
      of HO-1 in diabetic cardiomyopathy (DCM). In this study, we explored the role of
      HO-1 in myocardial dysfunction, myofibril structure, oxidative stress,
      inflammation, apoptosis and autophagy using a streptozotocin (STZ)-induced
      diabetes model in mice systemically overexpressing HO-1 (Tg-HO-1) or mutant HO-1
      (Tg-mutHO-1). The diabetic mouse model was induced by multiple peritoneal
      injections of STZ. Two months after injection, left ventricular (LV) function was
      measured by echocardiography. In addition, molecular biomarkers related to
      oxidative stress, inflammation, apoptosis and autophagy were evaluated using
      classical molecular biological/biochemical techniques. Mice with DCM exhibited
      severe LV dysfunction, myofibril structure disarray, aberrant cardiac oxidative
      stress, inflammation, apoptosis, autophagy and increased levels of HO-1. In
      addition, we determined that systemic overexpression of HO-1 ameliorated left
      ventricular dysfunction, myofibril structure disarray, oxidative stress,
      inflammation, apoptosis and autophagy in DCM mice. Furthermore, serine/threonine
      specific protein kinase (Akt) and AMP-activated protein kinase (AMPK)
      phosphorylation is normally inhibited in DCM, but overexpression of the HO-1 gene
      restored the phosphorylation of these kinases to normal levels. In contrast, the
      functions of HO-1 in DCM were significantly reversed by overexpression of mutant
      HO-1. This study underlines the unique roles of HO-1, including the inhibition of
      oxidative stress, inflammation and apoptosis and the enhancement of autophagy, in
      the pathogenesis of DCM. 

PMID- 24086667
TI  - Conjunctival inflammation in thrombospondin-1 deficient mouse model of Sjogren's
      syndrome.
AB  - Lacrimal gland inflammation during autoimmune Sjogren's syndrome (SS) leads to
      ocular surface inflammation - Keratoconjunctivitis sicca (KCS). This condition
      afflicts both the cornea and conjunctiva that form the ocular surface.
      Thrombospondin-1 (TSP-1) deficiency in mice results in lacrimal gland and corneal
      inflammation that resembles the human disease. In this study we report
      conjunctival pathology in this mouse model of SS. We found that TSP-1 null mice
      develop inflammation in the conjunctiva and associated loss of goblet cell
      function similar to that seen in patients with SS. Increased expression of Th1
      (IFN-gamma, TNF-alpha) and Th17 (IL-6, IL-17A) inflammatory cytokines and related
      transcription factors (Tbet and RORgammat) were detected in TSP-1 null
      conjunctiva as well as their draining lymph nodes (LNs). The conjunctival
      inflammation was also accompanied by an increase in local lymphatic vessels.
      Interestingly, migration of antigen-bearing dendritic cells (DCs) from the ocular
      surface to the LNs was dependent on the TSP-1 available in the tissue. These
      results not only reveal potential immunopathogenic mechanisms underlying KCS in
      SS but also highlight the therapeutic potential of TSP-1. 

PMID- 24086668
TI  - A VLP library of C-terminally truncated Hepatitis B core proteins: correlation of
      RNA encapsidation with a Th1/Th2 switch in the immune responses of mice.
AB  - An efficient pBR327- and Ptrp-based E. coli expression system was used to
      generate a large-scale library of virus like particles (VLP) formed by
      recombinant hepatitis B virus (HBV) core (HBc) protein derivatives. To construct
      the library, the gene of HBc protein of the genotype D/subtype ayw2 virus was
      gradually truncated from the 3'-end and twenty-two HBc variants (with truncation
      up to 139 aa) were expressed at high levels. The proteins were purified by salt
      precipitation and gel filtration. Background RNA binding was observed for VLPs
      formed by HBc1-149, which lacked all C-terminal Arg blocks, and the addition of
      three Arg residues (HBc1-152) only slightly increased RNA binding. The presence
      of two Arg blocks (proteins HBc1-162 and HBc1-163) resulted in approximately half
      of the typical level of RNA binding, and the presence of three blocks (protein
      HBc1-171) led to approximately 85% of the typical level of binding. Only a small
      increase in the level of RNA binding was found for the HBc1-175 VLPs, which
      contained all four Arg blocks but lacked the last 8 aa of the full-length HBc
      protein. VLPs containing high levels of RNA had higher antigenicity according to
      an ELISA with anti-HBc mAbs than the VLPs formed by HBc variants without C
      terminal Arg blocks and lacking RNA. The results indicate that the VLPs were
      stabilised by nucleic acids. The immunogenicity in BALB/c mice was comparable for
      VLPs formed by different HBc proteins, but a clear switch from a Th1 response to
      a Th2 response occurred after the loss of encapsidated RNA. We did not observe
      significant differences in lymphocyte proliferation in vitro for the tested VLP
      variants; however, the loss of RNA encapsidation correlated with a decreased
      level of IFN-gamma induction, which is a measure of the potential CTL activity of
      immunogens. 

PMID- 24086669
TI  - An improved targeted cAMP sensor to study the regulation of adenylyl cyclase 8 by
      Ca2+ entry through voltage-gated channels.
AB  - Here we describe an improved sensor with reduced pH sensitivity tethered to
      adenylyl cyclase (AC) 8. The sensor was used to study cAMP dynamics in the AC8
      microdomain of MIN6 cells, a pancreatic beta-cell line. In these cells, AC8 was
      activated by Ca(2+) entry through L-type voltage-gated channels following
      depolarisation. This activation could be reconstituted in HEK293 cells co
      expressing AC8 and either the alpha1C or alpha1D subunit of L-type voltage-gated
      Ca(2+) channels. The development of this improved sensor opens the door to the
      study of cAMP microdomains in excitable cells that have previously been
      challenging due to the sensitivity of fluorescent proteins to pH changes. 

PMID- 24086670
TI  - A structural equation model analysis of relationships among ENSO, seasonal
      descriptors and wildfires.
AB  - Seasonality drives ecological processes through networks of forcings, and the
      resultant complexity requires creative approaches for modeling to be successful.
      Recently ecologists and climatologists have developed sophisticated methods for
      fully describing seasons. However, to date the relationships among the variables
      produced by these methods have not been analyzed as networks, but rather with
      simple univariate statistics. In this manuscript we used structural equation
      modeling (SEM) to analyze a proposed causal network describing seasonality of
      rainfall for a site in south-central Florida. We also described how this network
      was influenced by the El Nino-Southern Oscillation (ENSO), and how the network in
      turn affected the site's wildfire regime. Our models indicated that wet and dry
      seasons starting later in the year (or ending earlier) were shorter and had less
      rainfall. El Nino conditions increased dry season rainfall, and via this effect
      decreased the consistency of that season's drying trend. El Nino conditions also
      negatively influenced how consistent the moistening trend was during the wet
      season, but in this case the effect was direct and did not route through
      rainfall. In modeling wildfires, our models showed that area burned was
      indirectly influenced by ENSO via its effect on dry season rainfall. Area burned
      was also indirectly reduced when the wet season had consistent rainfall, as such
      wet seasons allowed fewer wildfires in subsequent fire seasons. Overall area
      burned at the study site was estimated with high accuracy (R (2) score = 0.63).
      In summary, we found that by using SEMs, we were able to clearly describe causal
      patterns involving seasonal climate, ENSO and wildfire. We propose that similar
      approaches could be effectively applied to other sites where seasonality exerts
      strong and complex forcings on ecological processes. 

PMID- 24086671
TI  - Using next-generation sequencing to analyse the diet of a highly endangered land
      snail (Powelliphanta augusta) feeding on endemic earthworms.
AB  - Predation is often difficult to observe or quantify for species that are rare,
      very small, aquatic or nocturnal. The assessment of such species' diet can be
      conducted using molecular methods that target prey DNA remaining in predators'
      guts and faeces. These techniques do not require high taxonomic expertise, are
      applicable to soft-bodied prey and allow for identification at the species level.
      However, for generalist predators, the presence of mixed prey DNA in guts and
      faeces can be a major impediment as it requires development of specific primers
      for each potential prey species for standard (Sanger) sequencing. Therefore, next
      generation sequencing methods have recently been applied to such situations. In
      this study, we used 454-pyrosequencing to analyse the diet of
      Powelliphantaaugusta, a carnivorous landsnail endemic to New Zealand and
      critically endangered after most of its natural habitat has been lost to opencast
      mining. This species was suspected to feed mainly on earthworms. Although
      earthworm tissue was not detectable in snail faeces, earthworm DNA was still
      present in sufficient quantity to conduct molecular analyses. Based on faecal
      samples collected from 46 landsnails, our analysis provided a complete map of the
      earthworm-based diet of P. augusta. Predated species appear to be earthworms that
      live in the leaf litter or earthworms that come to the soil surface at night to
      feed on the leaf litter. This indicates that P. augusta may not be selective and
      probably predates any earthworm encountered in the leaf litter. These findings
      are crucial for selecting future translocation areas for this highly endangered
      species. The molecular diet analysis protocol used here is particularly
      appropriate to study the diet of generalist predators that feed on liquid or soft
      bodied prey. Because it is non-harmful and non-disturbing for the studied
      animals, it is also applicable to any species of conservation interest. 

PMID- 24086672
TI  - JNK and macroautophagy activation by bortezomib has a pro-survival effect in
      primary effusion lymphoma cells.
AB  - Understanding the mechanisms of autophagy induction and its role during
      chemotherapeutic treatments is of fundamental importance in order to manipulate
      it to improve the outcome of chemotherapy. In particular whether the bortezomib
      induced autophagy plays a pro-survival or pro-death role is still controversial.
      In this study we investigated if bortezomib induced endoplasmic reticulum (ER)
      stress and activated autophagy in Primary Effusion Lymphoma (PEL) cells and how
      they influenced cell survival. We found that bortezomib induced up-regulation of
      the pro-survival and pro-death ER stress molecules BIP and CHOP and activated c
      Jun NH2-terminal kinase (JNK), resulting in Bcl-2 phosphorylation and induction
      of autophagy. JNK and autophagy activation played a pro-survival role in this
      setting, thus their inhibition increased the bortezomib cytotoxic effect and PARP
      cleavage in PEL cells. Based on our results we suggest that the combination of
      bortezomib with JNK or autophagy inhibitors could be exploited to improve the
      outcome of therapy of this aggressive B cell lymphoma. 

PMID- 24086673
TI  - Microarray and degradome sequencing reveal microRNA differential expression
      profiles and their targets in Pinellia pedatisecta.
AB  - MicroRNAs (miRNAs) are endogenous small non-coding RNAs which play a critical
      role in gene regulation in plants. Pinelliapedatisecta is one of the most
      important herbs in traditional Chinese medicine, but there are no microRNAs of
      Pinelliapedatisecta were deposited in miRBase and the research of the related
      miRNA biological functions is still insufficient. To detect Pinelliapedatisecta
      miRNAs and discover their expression difference with Pinelliaternata, we carried
      out a microarray profiling. A total of 101 miRNAs belonging to 22 miRNA families
      were detected both in Pinelliapedatisecta and Pinelliaternata respectively, among
      them 21 miRNAs showed their differentially expression. GO (gene ontology) term
      enrichment analysis of the target genes of differential expression miRNAs reveal
      that these miRNAs mainly affect the reproduction, transcription factor activity
      and plant developmental process. To elucidate the target function of miRNAs, we
      constructed a degradome library from Pinellia pedatisecta leaf. The result showed
      that a total of 18 transcript were identified as targets of miRNAs and further
      analysis indicated that miR156 and miR529 may function together to repress SPL14.

PMID- 24086674
TI  - Cerulenin blockade of fatty acid synthase reverses hepatic steatosis in ob/ob
      mice.
AB  - Fatty liver or hepatic steatosis is a common health problem associated with
      abnormal liver function and increased susceptibility to ischemia/reperfusion
      injury. The objective of this study was to investigate the effect of the fatty
      acid synthase inhibitor cerulenin on hepatic function in steatotic ob/ob mice.
      Different dosages of cerulenin were administered intraperitoneally to ob/ob mice
      for 2 to 7 days. Body weight, serum AST/ALT, hepatic energy state, and gene
      expression patterns in ob/ob mice were examined. We found that cerulenin
      treatment markedly improved hepatic function in ob/ob mice. Serum AST/ALT levels
      were significantly decreased and hepatic ATP levels increased in treated obese
      mice compared to obese controls, accompanied by fat depletion in the hepatocyte.
      Expression of peroxisome proliferator-activated receptors alpha and gamma and
      uncoupling protein 2 were suppressed with cerulenin treatment and paralleled
      changes in AST/ALT levels. Hepatic glutathione content were increased in some
      cases and apoptotic activity in the steatotic livers was minimally changed with
      cerulenin treatment. In conclusion, these results demonstrate that fatty acid
      synthase blockade constitutes a novel therapeutic strategy for altering hepatic
      steatosis at non-stressed states in obese livers. 

PMID- 24086675
TI  - Lactate dehydrogenase a expression is necessary to sustain rapid angiogenesis of
      pulmonary microvascular endothelium.
AB  - Angiogenesis is a fundamental property of endothelium, yet not all endothelial
      cells display equivalent angiogenic responses; pulmonary microvascular
      endothelial cells undergo rapid angiogenesis when compared to endothelial cells
      isolated from conduit vessels. At present it is not clear how pulmonary
      microvascular endothelial cells fulfill the bioenergetic demands that are
      necessary to sustain such rapid blood vessel formation. We have previously
      established that pulmonary microvascular endothelial cells utilize aerobic
      glycolysis to generate ATP during growth, a process that requires the expression
      of lactate dehydrogenase A to convert pyruvate to lactate. Here, we test the
      hypothesis that lactate dehydrogenase A is required for pulmonary microvascular
      endothelial cells to sustain rapid angiogenesis. To test this hypothesis, Tet-On
      and Tet-Off conditional expression systems were developed in pulmonary
      microvascular endothelial cells, where doxycycline is utilized to induce lactate
      dehydrogenase A shRNA expression. Expression of LDH-A shRNA induced a time
      dependent decrease in LDH-A protein, which corresponded with a decrease in
      glucose consumption from the media, lactate production and cell growth; re
      expression of LDH-A rescued each of these parameters. LDH-A silencing greatly
      reduced network formation on Matrigel in vitro, and decreased blood vessel
      formation in Matrigel in vivo. These findings demonstrate that LDH-A is
      critically important for sustaining the rapid angiogenesis of pulmonary
      microvascular endothelial cells. 

PMID- 24086676
TI  - Neural representation of scale illusion: magnetoencephalographic study on the
      auditory illusion induced by distinctive tone sequences in the two ears.
AB  - The auditory illusory perception "scale illusion" occurs when a tone of ascending
      scale is presented in one ear, a tone of descending scale is presented
      simultaneously in the other ear, and vice versa. Most listeners hear illusory
      percepts of smooth pitch contours of the higher half of the scale in the right
      ear and the lower half in the left ear. Little is known about neural processes
      underlying the scale illusion. In this magnetoencephalographic study, we recorded
      steady-state responses to amplitude-modulated short tones having illusion
      inducing pitch sequences, where the sound level of the modulated tones was
      manipulated to decrease monotonically with increase in pitch. The steady-state
      responses were decomposed into right- and left-sound components by means of
      separate modulation frequencies. It was found that the time course of the
      magnitude of response components of illusion-perceiving listeners was
      significantly correlated with smooth pitch contour of illusory percepts and that
      the time course of response components of stimulus-perceiving listeners was
      significantly correlated with discontinuous pitch contour of stimulus percepts in
      addition to the contour of illusory percepts. The results suggest that the
      percept of illusory pitch sequence was represented in the neural activity in or
      near the primary auditory cortex, i.e., the site of generation of auditory steady
      state response, and that perception of scale illusion is maintained by automatic
      low-level processing. 

PMID- 24086677
TI  - Characterizing the role of brain derived neurotrophic factor genetic variation in
      Alzheimer's disease neurodegeneration.
AB  - There is accumulating evidence that neurotrophins, like brain-derived
      neurotrophic factor (BDNF), may impact aging and Alzheimer's Disease. However,
      traditional genetic association studies have not found a clear relationship
      between BDNF and AD. Our goal was to test whether BDNF single nucleotide
      polymorphisms (SNPs) impact Alzheimer's Disease-related brain imaging and
      cognitive markers of disease. We completed an imaging genetics study on 645
      Alzheimer's Disease Neuroimaging Initiative participants (ND=175, MCI=316,
      AD=154) who had cognitive, brain imaging, and genetics data at baseline and a
      subset of those with brain imaging data at two years. Samples were genotyped
      using the Illumina Human610-Quad BeadChip. 13 SNPs in BDNF were identified in the
      dataset following quality control measures (rs6265(Val66Met), rs12273363,
      rs11030094, rs925946, rs1050187, rs2203877, rs11030104, rs11030108, rs10835211,
      rs7934165, rs908867, rs1491850, rs1157459). We analyzed a subgroup of 8 SNPs that
      were in low linkage disequilibrium with each other. Automated brain morphometric
      measures were available through ADNI investigators, and we analyzed baseline
      cognitive scores, hippocampal and whole brain volumes, and rates of hippocampal
      and whole brain atrophy and rates of change in the ADAS-Cog over one and two
      years. Three out of eight BDNF SNPs analyzed were significantly associated with
      measures of cognitive decline (rs1157659, rs11030094, rs11030108). No SNPs were
      significantly associated with baseline brain volume measures, however six SNPs
      were significantly associated with hippocampal and/or whole brain atrophy over
      two years (rs908867, rs11030094, rs6265, rs10501087, rs1157659, rs1491850). We
      also found an interaction between the BDNF Val66Met SNP and age with whole brain
      volume. Our imaging-genetics analysis in a large dataset suggests that while BDNF
      genetic variation is not specifically associated with a diagnosis of AD, it
      appears to play a role in AD-related brain neurodegeneration. 

PMID- 24086678
TI  - SQSTM1/p62 interacts with HDAC6 and regulates deacetylase activity.
AB  - Protein aggregates can form in the cytoplasm of the cell and are accumulated at
      aggresomes localized to the microtubule organizing center (MTOC) where they are
      subsequently degraded by autophagy. In this process, aggregates are engulfed into
      autophagosomes which subsequently fuse with lysosomes for protein degradation. A
      member of the class II histone deacetylase family, histone deacetylase 6(HDAC6)
      has been shown to be involved in both aggresome formation and the fusion of
      autophagosomes with lysosomes making it an attractive target to regulate protein
      aggregation. The scaffolding protein sequestosome 1(SQSTM1)/p62 has also been
      shown to regulate accumulation and autophagic clearance of protein aggregates.
      Recent studies have revealed colocalization of HDAC6 and p62 to ubiquitinated
      mitochondria, as well as, ubiquitinated protein aggregates associated with the E3
      ubiquitin ligase TRIM50. HDAC6 deacetylase activity is required for aggresome
      formation and can be regulated by protein interaction with HDAC6. Due to their
      colocalization at ubiquitinated protein aggregates, we sought to examine if p62
      specifically interacted with HDAC6 and if so, if this interaction had any effect
      on HDAC6 activity and/or the physiological function of cortactin-F-actin
      assembly. We succeeded in identifying and mapping the direct interaction between
      HDAC6 and p62. We further show that this interaction regulates HDAC6 deacetylase
      activity. Data are presented demonstrating that the absence of p62 results in
      hyperactivation of HDAC6 and deacetylation of alpha-tubulin and cortactin.
      Further, upon induction of protein misfolding we show that p62 is required for
      perinuclear co-localization of cortactin-F-actin assemblies. Thus, our findings
      indicate that p62 plays a key role in regulating the recruitment of F-actin
      network assemblies to the MTOC, a critical cellular function that is required for
      successful autophagic clearance of protein aggregates. 

PMID- 24086679
TI  - A strategy for synthesis of pathogenic human immunoglobulin free light chains in
      E. coli.
AB  - Monoclonal immunoglobulin light chains are normally synthesized in excess
      compared to the heavy chain partners and can be detected in serum and urine
      ("free" LC). Occasionally free LC are per se cause of organ toxicity, as in free
      LC-related disorders. In AL amyloidosis, the most common of these conditions,
      free LC with peculiar biophysical properties related to their primary structure
      damage target organs and organize in amyloid fibrils. Unlimited availability of
      well-characterized free LC is instrumental to investigate the toxic effect of
      these proteins and to study their interactions with targets. We present a
      straightforward strategy to obtain recombinant monoclonal free LC by using a
      bacterial system. These proteins, expressed as inclusion bodies, were subjected
      to solubilization and refolding procedures to recover them in native form. To
      minimize differences from the circulating natural LC, full-length recombinant LC
      were expressed, i.e. complete of variable and constant regions, with the original
      amino acid sequence along the entire protein, and with no purification tags. The
      strategy was exploited to generate free LC from three AL amyloidosis patients.
      After purification, recombinant proteins were biochemically characterized and
      compared to the natural Bence Jones protein isolated from one of the patients.
      Results showed that the recombinant free LC were properly folded and formed
      homodimers in solution, similar to the natural Bence Jones protein used for
      comparison. Furthermore, as proof of pathogenicity, recombinant proteins formed
      amyloid fibrils in vitro. We believe that the present strategy represents a
      valuable tool to speed research in free LC-related disorders. 

PMID- 24086680
TI  - Heart wall is thicker on postmortem computed tomography than on antemortem
      [corrected] computed tomography: the first longitudinal study.
AB  - OBJECTIVE: To evaluate the postmortem changes of the heart wall on postmortem
      (PM) computed tomography (CT) in comparison with those on ante mortem CT (AMCT),
      and in comparison with the pathological findings, obtained in the same patients.
      MATERIALS AND METHODS: We studied 57 consecutive patients who had undergone AMCT,
      PMCT, and pathological autopsy in our tertiary care hospital between April 2009
      and December 2010. PMCT was performed within 20 hours after death, followed by
      pathological autopsy. The cardiac chambers were measured at five sites on both
      AMCT and PMCT by two board-certified radiologists who were not provided with
      clinical information. The differences in heart wall thickness between AMCT with
      and without contrast medium, between AMCT and PMCT, and between PMCT and
      pathological anatomy were evaluated statistically. Confounding factors of
      postmortem change such as gender, presence of arteriosclerosis, the organ related
      to cause of death, age, and elapsed time since death were examined statistically.
      RESULTS: No significant differences were observed on AMCT in comparison of
      contrasted and non-contrasted images. The heart wall was significantly thicker on
      PMCT than on AMCT (p < 0.0001) at all five measurement sites. The heart wall was
      significantly thicker on PMCT than on pathology specimens when measured in
      accordance with pathological standard mensuration. However, no significant
      difference was observed between PMCT measurements and those of pathology
      specimens at any site when the papillary muscles and epicardial fat were
      included. No significant association was found between postmortem change in heart
      wall thickness and gender, presence of arteriosclerosis, the organ related to
      cause of death, age, or elapsed time since death. CONCLUSION: This is the first
      longitudinal study to confirm greater thickness of heart wall on postmortem
      images compared with ante mortem images, in the same patients. Furthermore, the
      postmortem changes on CT were supported by the pathological findings.

PMID- 24086681
TI  - Why does Amphibian Chytrid (Batrachochytrium dendrobatidis) not occur everywhere?
      An exploratory study in Missouri ponds.
AB  - The amphibian chytrid fungus, Batrachochytrium dendrobatidis (Bd), is a globally
      emerging pathogen that has caused widespread amphibian population declines,
      extirpations, and extinctions. However, Bd does not occur in all apparently
      suitable amphibian populations, even within regions where it is widespread, and
      it is often unclear why Bd occurs in some habitats but not others. In this study,
      we rigorously surveyed the amphibian and invertebrate biodiversity of 29 ponds in
      Missouri, screened resident amphibian larvae (Rana (Lithobates) sp.) for Bd
      infection, and characterized the aquatic physiochemical environment of each pond
      (temperature pH, conductivity, nitrogen, phosphorus, and chlorophyll-a). Our goal
      was to generate hypotheses toward answering the question, "Why does Bd not occur
      in all apparently suitable habitats?" Bd occurred in assayed amphibians in 11 of
      the 29 ponds in our study area (38% of ponds). We found no significant
      relationship between any single biotic or abiotic variable and presence of Bd.
      However, multivariate analyses (nonmetric multidimensional scaling and
      permutational tests of dispersion) revealed that ponds in which Bd occurred were
      a restricted subset of all ponds in terms of amphibian community structure,
      macroinvertebrate community structure, and pond physiochemistry. In other words,
      Bd ponds from 6 different conservation areas were more similar to each other than
      would be expected based on chance. The results of a structural equation model
      suggest that patterns in the occurrence of Bd among ponds are primarily
      attributable to variation in macroinvertebrate community structure. When combined
      with recent results showing that Bd can infect invertebrates as well as
      amphibians, we suggest that additional research should focus on the role played
      by non-amphibian biota in determining the presence, prevalence, and pathogenicity
      of Bd in amphibian populations. 

PMID- 24086682
TI  - Establishment and evaluation of a stable cattle type II alveolar epithelial cell
      line.
AB  - Macrophages and dendritic cells are recognized as key players in the defense
      against mycobacterial infection. Recent research has confirmed that alveolar
      epithelial cells (AECs) also play important roles against mycobacterium
      infections. Thus, establishing a stable cattle AEC line for future endogenous
      immune research on bacterial invasion is necessary. In the present study, we
      first purified and immortalized type II AECs (AEC II cells) by transfecting them
      with a plasmid containing the human telomerase reverse trancriptase gene. We then
      tested whether or not the immortalized cells retained the basic physiological
      properties of primary AECs by reverse-transcription polymerase chain reaction and
      Western blot. Finally, we tested the secretion capacity of immortalized AEC II
      cells upon stimulation by bacterial invasion. The cattle type II alveolar
      epithelial cell line (HTERT-AEC II) that we established retained lung epithelial
      cell characteristics: the cells were positive for surfactants A and B, and they
      secreted tumor necrosis factor-alpha and interleukin-6 in response to bacterial
      invasion. Thus, the cell line we established is a potential tool for research on
      the relationship between AECs and Mycobacterium tuberculosis. 

PMID- 24086683
TI  - Anti-HIV activity of human defensin 5 in primary CD4+ T cells under serum
      deprived conditions is a consequence of defensin-mediated cytotoxicity.
AB  - BACKGROUND: We have previously shown that human defensin 5 (HD5) promotes HIV
      infectivity in both primary CD4+ T cells and HeLa cells expressing CD4 and CCR5.
      HD5 is induced in response to sexually transmitted infections (STIs) such as
      Chlamydia trachomatis and Neisseria gonorrhoeae, suggesting it plays a role in
      STI-mediated enhancement of HIV transmission. In contrast to our findings, a
      recent study reports that HD5 has an anti-HIV effect in primary CD4+ T cells
      under serum-deprived conditions. To resolve these apparently contradictory
      observations, we investigated experimental parameters that might contribute to
      contrasting effects of HD5. RESULTS: Serum-deprived culture conditions were
      associated with anti-HIV activity. In contrast to the dependence of the HIV
      enhancing effect on HD5 structure, the anti-HIV activity in serum-deprived
      primary CD4+ T cells was independent of HD5 structure as the linear peptide [Abu]
      HD5 exhibited similar anti-HIV activity. Under serum deprived conditions, HD5
      blocked CD4-receptor-independent HIV-1vsv infection before or after viral entry.
      We found that HD5 and its linear form induced significant cell death in primary
      CD4+ T cells under serum-deprived culture conditions. HD5-mediated apoptosis was
      observed as early as 2 h after addition of defensins to serum-deprived primary
      CD4+ T cells. In contrast to primary CD4+ T cells, HD5 did not induce
      cytotoxicity and promote HIV infectivity of HeLa-CD4-CCR5 cells under serum
      deprived conditions. CONCLUSIONS: These results indicate that under serum
      deprived culture conditions HD5 is toxic for primary CD4+ T cells, warranting
      caution in data interpretation.

PMID- 24086684
TI  - Quantifying the fitness advantage of polymerase substitutions in Influenza A/H7N9
      viruses during adaptation to humans.
AB  - Adaptation of zoonotic influenza viruses towards efficient human-to-human
      transmissibility is a substantial public health concern. The recently emerged
      A/H7N9 influenza viruses in China provide an opportunity for quantitative studies
      of host-adaptation, as human-adaptive substitutions in the PB2 gene of the virus
      have been found in all sequenced human strains, while these substitutions have
      not been detected in any non-human A/H7N9 sequences. Given the currently
      available information, this observation suggests that the human-adaptive PB2
      substitution might confer a fitness advantage to the virus in these human hosts
      that allows it to rise to proportions detectable by consensus sequencing over the
      course of a single human infection. We use a mathematical model of within-host
      virus evolution to estimate the fitness advantage required for a substitution to
      reach predominance in a single infection as a function of the duration of
      infection and the fraction of mutant present in the virus population that
      initially infects a human. The modeling results provide an estimate of the lower
      bound for the fitness advantage of this adaptive substitution in the currently
      sequenced A/H7N9 viruses. This framework can be more generally used to
      quantitatively estimate fitness advantages of adaptive substitutions based on the
      within-host prevalence of mutations. Such estimates are critical for models of
      cross-species transmission and host-adaptation of influenza virus infections. 

PMID- 24086685
TI  - S100A14 interacts with S100A16 and regulates its expression in human cancer
      cells.
AB  - Both S100A14 and S100A16 are members of the multifunctional S100 protein family.
      Formation of homo/heterodimers is considered to be one of the major mechanisms
      for S100 proteins to execute their diverse cellular functions. By employing a
      classical Yeast two hybrid (Y-2 H) screen, we identified S100A16 as the single
      interaction partner of S100A14. This interaction was verified by co
      immunoprecipitation, double indirect immunofluorescence and double immunostaining
      in specimens of oral squamous cell carcinoma and normal oral mucosa. The
      functional significance of this interaction was examined by employing retroviral
      mediated over-expression and knock-down of these proteins in several cancer cell
      lines. Over-expression and knock-down of S100A14 led to concomitant up- and down
      regulation of S100A16 protein in the cell-lines examined. However, there was no
      up-regulation of S100A16 mRNA upon S100A14 over-expression, indicating that
      modulation of S100A16 expression was not due to enhanced transcriptional activity
      but possibly by post-transcriptional regulation. In contrary, over-expression of
      S100A16 was associated neither with the up-regulation of S100A14 mRNA nor its
      protein, suggesting a unidirectional regulation between S100A14 and S100A16.
      Cellular treatment with protein synthesis inhibitor cycloheximide demonstrated a
      time-dependent intracellular degradation of both S100A16 and S100A14 proteins.
      Additionally, regulation of S100A16 and S100A14 degradation was found to be
      independent of the classical proteasomal and lysosomal pathways of protein
      degradation. Further studies will therefore be necessary to understand the
      functional significance of this interaction and the mechanisms on how S100A14 is
      involved in the regulation of S100A16 expression. 

PMID- 24086686
TI  - Verification of intraovum transmission of a microsporidium of vertebrates:
      Pseudoloma neurophilia infecting the Zebrafish, Danio rerio.
AB  - Direct transmission from parents to offspring, referred to as vertical
      transmission, occurs within essentially all major groups of pathogens. Several
      microsporidia (Phylum Microsporidia) that infect arthropods employ this mode of
      transmission, and various lines of evidence have suggested this might occur with
      certain fish microsporidia. The microsporidium, Pseudoloma neurophilia, is a
      common pathogen of the laboratory zebrafish, Danio rerio. We previously verified
      that this parasite is easily transmitted horizontally, but previous studies also
      indicated that maternal transmission occurs. We report here direct observation of
      Pseudoloma neurophilia in the progeny of infected zebrafish that were reared in
      isolation, including microscopic visualization of the parasite in all major
      stages of development. Histological examination of larval fish reared in
      isolation from a group spawn showed microsporidian spores in the resorbing yolk
      sac of a fish. Infections were also observed in three of 36 juvenile fish. Eggs
      from a second group spawn of 30 infected fish were examined using a
      stereomicroscope and the infection was observed from 4 to 48 hours post
      fertilization in two embryos. Intraovum infections were detected in embryos from
      4 of 27 pairs of infected fish that were spawned based on qPCR detection of P.
      neurophilia DNA. The prevalence of intraovum infections from the four spawns
      containing infected embryos was low (~1%) based on calculation of prevalence
      using a maximum likelihood analysis for pooled samples. Parasite DNA was detected
      in the water following spawning of 11 of the infected pairs, suggesting there was
      also potential for extraovum transmission in these spawning events. Our study
      represents the first direct observation of vertical transmission within a
      developing embryo of a microsporidian parasite in a vertebrate. The low
      prevalence of vertical transmission in embryos is consistent with observations of
      some other fish pathogens that are also readily transmitted by both vertical and
      horizontal routes. 

PMID- 24086687
TI  - Heterogeneous cerebral vasoreactivity dynamics in patients with carotid stenosis.
AB  - Cerebral vasoreactivity (CVR) can be assessed by functional MRI (fMRI) using
      hypercapnia challenges. In normal subjects, studies have shown temporal
      variability of CVR blood oxygenation level-dependent responses among different
      brain regions. In the current study, we analyzed the variability of BOLD CVR
      dynamics by fMRI with a breath-holding task in 17 subjects with unilateral
      carotid stenosis before they received carotid stenting. Great heterogeneity of
      CVR dynamics was observed when comparing BOLD responses between ipsilateral and
      contralateral hemispheres in each patient, especially in middle cerebral artery
      (MCA) territories. While some subjects (n=12) had similar CVR responses between
      either hemisphere, the others (n=5) had a poorly correlated pattern of BOLD
      changes between ipsilateral and contralateral hemispheres. In the latter group,
      defined as impaired CVR, post-stenting perfusion tended to be more significantly
      increased. Our data provides the first observation of divergent temporal BOLD
      responses during breath holding in patients with carotid stenosis. The
      development of collateral circulation and the derangement of cerebral
      hemodynamics can be detected through this novel analysis of the different
      patterns of BOLD changes. The results also help in prediction of robust increase
      of perfusion or hyperperfusion after carotid stenting. 

PMID- 24086688
TI  - Vocal recruitment for joint travel in wild chimpanzees.
AB  - Joint travel is a common social activity of many group-living animals, which
      requires some degree of coordination, sometimes through communication signals.
      Here, we studied the use of an acoustically distinct vocalisation in chimpanzees,
      the 'travel hoo', a signal given specifically in the travel context. We were
      interested in how this call type was produced to coordinate travel, whether it
      was aimed at specific individuals and how recipients responded. We found that
      'travel hoos' were regularly given prior to impending departures and that silent
      travel initiations were less successful in recruiting than vocal initiations.
      Other behaviours associated with departure were unrelated to recruitment,
      suggesting that 'travel hoos' facilitated joint travel. Crucially, 'travel hoos'
      were more often produced in the presence of allies than other individuals, with
      high rates of recruitment success. We discuss these findings as evidence for how
      motivation to perform a specific social activity can lead to the production of a
      vocal signal that qualifies as 'intentional' according to most definitions,
      suggesting that a key psychological component of human language may have already
      been present in the common ancestor of chimpanzees and humans. 

PMID- 24086689
TI  - AAV-mediated, optogenetic ablation of Muller Glia leads to structural and
      functional changes in the mouse retina.
AB  - Muller glia, the primary glial cell in the retina, provide structural and
      metabolic support for neurons and are essential for retinal integrity. Muller
      cells are closely involved in many retinal degenerative diseases, including
      macular telangiectasia type 2, in which impairment of central vision may be
      linked to a primary defect in Muller glia. Here, we used an engineered, Muller
      specific variant of AAV, called ShH10, to deliver a photo-inducibly toxic
      protein, KillerRed, to Muller cells in the mouse retina. We characterized the
      results of specific ablation of these cells on visual function and retinal
      structure. ShH10-KillerRed expression was obtained following intravitreal
      injection and eyes were then irradiated with green light to induce toxicity.
      Induction of KillerRed led to loss of Muller cells and a concomitant decrease of
      Muller cell markers glutamine synthetase and cellular retinaldehyde-binding
      protein, reduction of rhodopsin and cone opsin, and upregulation of glial
      fibrillary acidic protein. Loss of Muller cells also resulted in retinal
      disorganization, including thinning of the outer nuclear layer and the
      photoreceptor inner and outer segments. High resolution imaging of thin sections
      revealed displacement of photoreceptors from the ONL, formation of rosette-like
      structures and the presence of phagocytic cells. Furthermore, Muller cell
      ablation resulted in increased area and volume of retinal blood vessels, as well
      as the formation of tortuous blood vessels and vascular leakage.
      Electrophysiologic measures demonstrated reduced retinal function, evident in
      decreased photopic and scotopic electroretinogram amplitudes. These results show
      that loss of Muller cells can cause progressive retinal degenerative disease, and
      suggest that AAV delivery of an inducibly toxic protein in Muller cells may be
      useful to create large animal models of retinal dystrophies. 

PMID- 24086690
TI  - Tuberculosis outcomes in Papua, Indonesia: the relationship with different body
      mass index characteristics between papuan and non-Papuan ethnic groups.
AB  - Weight gain achieved during pulmonary tuberculosis (PTB) treatment is associated
      with the likelihood of bacteriological treatment success. It is recognised that
      weight and body mass index (BMI) characteristics differ between ethnic groups in
      health and illness states. However there has been no prior investigation of how
      ethnic differences in BMI might influence tuberculosis treatment outcome. Our aim
      was to investigate predictors of microbiological response to PTB treatment at the
      Tuberculosis Clinic in Timika, Papua Province, Indonesia and specifically, to
      determine the contribution of ethnicity. The population comprises two distinct
      ethnic groups - Asian (Non-Papuan) and Melanesian (Papuan). We conducted a
      prospective study of adults with smear-positive PTB. Treatment outcomes were 1-
      and 2-month sputum culture and time to microscopy conversion. Clinical measures
      included weight, BMI, chest radiograph, pulmonary function including forced
      expiratory volume in 1 second (FEV1) and haemoglobin. One hundred eighty six
      participants (83 Papuan, 103 non-Papuan Indonesians) were enrolled. At baseline,
      Papuans had higher mean weight and BMI than non-Papuans (50.0 kg versus 46.9 kg,
      p = 0.006 and 20.0 kg/m2 versus 18.7 kg/m2, p = 0.001 respectively). This was
      despite having lower mean haemoglobin (11.3 vs 13.1 g/dL, p<0.0001), higher
      smoking and HIV rates (37% vs 21%, p = 0.02 and 20% vs 5%, p = 0.01 respectively)
      and longer median illness duration (3 vs 2 months, p = 0.04), but similar
      radiological severity (proportion with cavities 55% vs 57%, p = 0.7), sputum
      smear grade (p = 0.3) and mean % predicted FEV1 (63% vs 64%, p = 0.7). By 2
      months, Papuans had gained still more weight (mean 5.9 vs 4.2 kg, p = 0.02), and
      were more likely to have negative sputum culture (49/56 vs 45/67, p = 0.02), in
      univariable and multivariable analyses controlling for other likely determinants
      of culture conversion. In conclusion, Papuans had better early microbiological
      outcome from PTB treatment, which may relate to better preservation of weight and
      greater early weight gain. 

PMID- 24086691
TI  - Lymphatic vascular response to acute inflammation.
AB  - During acute inflammation, functioning lymphatics are believed to reduce edema
      and to provide a transiting route for immune cells, but the extent at which the
      dermal lymphatic remodeling impacts lymphatic transport or the factors regulating
      these changes remains unclear. Herein we quantify the increase in lymphatic
      endothelial cells (LECs) and examine the expression of pro-angiogenenic and
      lymphangiogenic factors during acute cutaneous hypersensitivity (CHS). We found
      that LECs actively proliferate during CHS but that this proliferation does not
      affect the lymphatic vessel density. Instead, lymphatic remodeling is accompanied
      by lymphatic vessel leakiness and lower ejection of lymph fluid, which is
      observed only in the proximal lymphatic vessel draining the inflamed area. LECs
      and the immune cells release growth factors and cytokines during inflammation,
      which impact the lymphatic microenvironment and function. We identified that FGF
      2, PLGF-2, HGF, EGF, and KC/CXCL17 are differentially expressed within tissues
      during acute CHS, but both VEGF-C and VEGF-D levels do not significantly change.
      Our results indicate that VEGF-C and VEGF-D are not the only players and other
      factors may be responsible for the LECs proliferation and altered lymphatic
      function in acute CHS. 

PMID- 24086693
TI  - Tamoxifen inhibition of kv7.2/kv7.3 channels.
AB  - KCNQ genes encode five Kv7 K(+) channel subunits (Kv7.1-Kv7.5). Four of these
      (Kv7.2-Kv7.5) are expressed in the nervous system. Kv7.2 and Kv7.3 are the
      principal molecular components of the slow voltage-gated M-channel, which
      regulates neuronal excitability. In this study, we demonstrate that tamoxifen, an
      estrogen receptor antagonist used in the treatment of breast cancer, inhibits
      Kv7.2/Kv7.3 currents heterologously expressed in human embryonic kidney HEK-293
      cells. Current inhibition by tamoxifen was voltage independent but concentration
      dependent. The IC50 for current inhibition was 1.68 +/- 0.44 uM. The voltage
      dependent activation of the channel was not modified. Tamoxifen inhibited Kv7.2
      homomeric channels with a higher potency (IC50 = 0.74 +/- 0.16 uM). The mutation
      Kv7.2 R463E increases phosphatidylinositol- 4,5-bisphosphate (PIP2) - channel
      interaction and diminished dramatically the inhibitory effect of tamoxifen
      compared with that for wild type Kv7.2. Conversely, the mutation Kv7.2 R463Q,
      which decreases PIP2 -channel interaction, increased tamoxifen potency. Similar
      results were obtained on the heteromeric Kv7.2 R463Q/Kv7.3 and Kv7.2 R463E/Kv7.3
      channels, compared to Kv7.2/Kv7.3 WT. Overexpression of type 2A PI(4)P5-kinase
      (PIP5K 2A) significantly reduced tamoxifen inhibition of Kv7.2/Kv7.3 and Kv7.2
      R463Q channels. Our results suggest that tamoxifen inhibited Kv7.2/Kv7.3 channels
      by interfering with PIP2-channel interaction because of its documented
      interaction with PIP2 and the similar effect of tamoxifen on various PIP2
      sensitive channels. 

PMID- 24086692
TI  - The voltage-gated sodium channel nav1.8 is expressed in human sperm.
AB  - The role of Na(+) fluxes through voltage-gated sodium channels in the regulation
      of sperm cell function remains poorly understood. Previously, we reported that
      several genes encoding voltage-gated Na(+) channels were expressed in human
      testis and mature spermatozoa. In this study, we analyzed the presence and
      function of the TTX-resistant VGSC alpha subunit Nav1.8 in human capacitated
      sperm cells. Using an RT-PCR assay, we found that the mRNA of the gene SCN10A,
      that encode Na v1.8, was abundantly and specifically expressed in human testis
      and ejaculated spermatozoa. The Na v1.8 protein was detected in capacitated sperm
      cells using three different specific antibodies against this channel. Positive
      immunoreactivity was mainly located in the neck and the principal piece of the
      flagellum. The presence of Na v1.8 in sperm cells was confirmed by Western blot.
      Functional studies demonstrated that the increases in progressive motility
      produced by veratridine, a voltage-gated sodium channel activator, were reduced
      in sperm cells preincubated with TTX (10 MUM), the Na v1.8 antagonist A-803467,
      or a specific Na v1.8 antibody. Veratridine elicited similar percentage increases
      in progressive motility in sperm cells maintained in Ca(2+)-containing or Ca(2+)
      free solution and did not induce hyperactivation or the acrosome reaction.
      Veratridine caused a rise in sperm intracellular Na(+), [Na(+)]i, and the
      sustained phase of the response was inhibited in the presence of A-803467. These
      results verify that the Na(+) channel Na v1.8 is present in human sperm cells and
      demonstrate that this channel participates in the regulation of sperm function. 

PMID- 24086694
TI  - From income to capital breeding: when diversified strategies sustain species
      coexistence.
AB  - There is empirical evidence of many diversified ways for energy to be acquired
      and allocated to reproduction, notably with strategies ranging from strict income
      breeding (females fueling their gametes with energy gained concomitantly during
      reproduction) to strict capital breeding (females storing nutrients prior
      reproduction). Until now, the question of whether diversification of these
      strategies might impact the way communities are organized has not been
      considered. Here, we suggest that diversified resource allocation strategies
      among competing species may contribute to their coexistence. We examined this
      hypothesis by focusing on communities composed of four phytophagous insect
      species that coexist and compete for egg-laying sites. From wild-caught females,
      we determined precisely the breeding period of each species and we described
      their resource acquisition and allocation to reproduction dynamics. We quantified
      in each species the total amount of larval energy stored by newly-emerging
      females and then monitored the total energy budget of females caught in the field
      before and throughout their breeding period. We found that the four sibling
      weevil species are markedly segregated along the income-capital-breeding
      continuum, which is correlated with clear time partitioning in their laying
      activity. Our results suggest that diversified resource allocation strategies
      might contribute to time partitioning of plant resources exploitation and thus
      indirectly to their coexistence. This work should further encourage studies
      examining the extent to which competitive coexistence might be affected by
      diversification of income-capital breeding strategies together with the intensity
      of interspecific competition, and considering the divergent evolution of these
      strategies. 

PMID- 24086695
TI  - Meaning making in cancer survivors: a focus group study.
AB  - BACKGROUND: Confrontation with a life-threatening disease like cancer can evoke
      existential distress, which can trigger a search for meaning in people after
      having survived this disease. METHODS: In an effort to gain more insight in the
      meaning making process, we conducted four focus groups with 23 cancer survivors
      on this topic. Participants responded to questions about experienced meaning
      making, perceived changes in meaning making after cancer and the perceived need
      for help in this area. RESULTS: Most frequently mentioned meaning making themes
      were relationships and experiences. We found that, in general, cancer survivors
      experienced enhanced meaning after cancer through relationships, experiences,
      resilience, goal-orientation and leaving a legacy. Some participants, however,
      also said to have (also) experienced a loss of meaning in their lives through
      experiences, social roles, relationships and uncertainties about the future.
      CONCLUSIONS: The results indicated that there is a group of cancer survivors that
      has succeeded in meaning making efforts, and experienced sometimes even more
      meaning in life than before diagnosis, while there is also a considerable group
      of survivors that struggled with meaning making and has an unmet need for help
      with that. The results of this study contribute to develop a meaning centered
      intervention for cancer survivors.

PMID- 24086696
TI  - Visualization and quantification of APP intracellular domain-mediated nuclear
      signaling by bimolecular fluorescence complementation.
AB  - BACKGROUND: The amyloid precursor protein (APP) intracellular domain (AICD) is
      released from full-length APP upon sequential cleavage by either alpha- or beta
      secretase followed by gamma-secretase. Together with the adaptor protein Fe65 and
      the histone acetyltransferase Tip60, AICD forms nuclear multiprotein complexes
      (AFT complexes) that function in transcriptional regulation. OBJECTIVE: To
      develop a medium-throughput machine-based assay for visualization and
      quantification of AFT complex formation in cultured cells. METHODS: We used
      cotransfection of bimolecular fluorescence complementation (BiFC) fusion
      constructs of APP and Tip60 for analysis of subcellular localization by confocal
      microscopy and quantification by flow cytometry (FC). RESULTS: Our novel BiFC
      constructs show a nuclear localization of AFT complexes that is identical to
      conventional fluorescence-tagged constructs. Production of the BiFC signal is
      dependent on the adaptor protein Fe65 resulting in fluorescence complementation
      only after Fe65-mediated nuclear translocation of AICD and interaction with
      Tip60. We applied the AFT-BiFC system to show that the Swedish APP familial
      Alzheimer's disease mutation increases AFT complex formation, consistent with the
      notion that AICD mediated nuclear signaling mainly occurs following APP
      processing through the amyloidogenic beta-secretase pathway. Next, we studied the
      impact of posttranslational modifications of AICD on AFT complex formation.
      Mutation of tyrosine 682 in the YENPTY motif of AICD to phenylalanine prevents
      phosphorylation resulting in increased nuclear AFT-BiFC signals. This is
      consistent with the negative impact of tyrosine phosphorylation on Fe65 binding
      to AICD. Finally, we studied the effect of oxidative stress. Our data shows that
      oxidative stress, at a level that also causes cell death, leads to a reduction in
      AFT-BiFC signals. CONCLUSION: We established a new method for visualization and
      FC quantification of the interaction between AICD, Fe65 and Tip60 in the nucleus
      based on BiFC. It enables flow cytometric analysis of AICD nuclear signaling and
      is characterized by scalability and low background fluorescence.

PMID- 24086697
TI  - Ginger extract inhibits biofilm formation by Pseudomonas aeruginosa PA14.
AB  - Bacterial biofilm formation can cause serious problems in clinical and industrial
      settings, which drives the development or screening of biofilm inhibitors. Some
      biofilm inhibitors have been screened from natural products or modified from
      natural compounds. Ginger has been used as a medicinal herb to treat infectious
      diseases for thousands of years, which leads to the hypothesis that it may
      contain chemicals inhibiting biofilm formation. To test this hypothesis, we
      evaluated ginger's ability to inhibit Pseudomonas aeruginosa PA14 biofilm
      formation. A static biofilm assay demonstrated that biofilm development was
      reduced by 39-56% when ginger extract was added to the culture. In addition,
      various phenotypes were altered after ginger addition of PA14. Ginger extract
      decreased production of extracellular polymeric substances. This finding was
      confirmed by chemical analysis and confocal laser scanning microscopy.
      Furthermore, ginger extract formed noticeably less rugose colonies on agar plates
      containing Congo red and facilitated swarming motility on soft agar plates. The
      inhibition of biofilm formation and the altered phenotypes appear to be linked to
      a reduced level of a second messenger, bis-(3'-5')-cyclic dimeric guanosine
      monophosphate. Importantly, ginger extract inhibited biofilm formation in both
      Gram-positive and Gram-negative bacteria. Also, surface biofilm cells formed with
      ginger extract detached more easily with surfactant than did those without ginger
      extract. Taken together, these findings provide a foundation for the possible
      discovery of a broad spectrum biofilm inhibitor. 

PMID- 24086698
TI  - Dosage considerations for transcranial direct current stimulation in children: a
      computational modeling study.
AB  - Transcranial direct current stimulation (tDCS) is being widely investigated in
      adults as a therapeutic modality for brain disorders involving abnormal cortical
      excitability or disordered network activity. Interest is also growing in studying
      tDCS in children. Limited empirical studies in children suggest that tDCS is well
      tolerated and may have a similar safety profile as in adults. However, in
      electrotherapy as in pharmacotherapy, dose selection in children requires special
      attention, and simple extrapolation from adult studies may be inadequate.
      Critical aspects of dose adjustment include 1) differences in neurophysiology and
      disease, and 2) variation in brain electric fields for a specified dose due to
      gross anatomical differences between children and adults. In this study, we used
      high-resolution MRI derived finite element modeling simulations of two healthy
      children, ages 8 years and 12 years, and three healthy adults with varying head
      size to compare differences in electric field intensity and distribution.
      Multiple conventional and high-definition tDCS montages were tested. Our results
      suggest that on average, children will be exposed to higher peak electrical
      fields for a given applied current intensity than adults, but there is likely to
      be overlap between adults with smaller head size and children. In addition,
      exposure is montage specific. Variations in peak electrical fields were seen
      between the two pediatric models, despite comparable head size, suggesting that
      the relationship between neuroanatomic factors and bioavailable current dose is
      not trivial. In conclusion, caution is advised in using higher tDCS doses in
      children until 1) further modeling studies in a larger group shed light on the
      range of exposure possible by applied dose and age and 2) further studies
      correlate bioavailable dose estimates from modeling studies with empirically
      tested physiologic effects, such as modulation of motor evoked potentials after
      stimulation. 

PMID- 24086700
TI  - Structural layers of ex vivo rat hippocampus at 7T MRI.
AB  - Magnetic resonance imaging (MRI) applied to the hippocampus is challenging in
      studies of the neurophysiology of memory and the physiopathology of numerous
      diseases such as epilepsy, Alzheimer's disease, ischemia, and depression. The
      hippocampus is a well-delineated cerebral structure with a multi-layered
      organization. Imaging of hippocampus layers is limited to a few studies and
      requires high magnetic field and gradient strength. We performed one conventional
      MRI sequence on a 7T MRI in order to visualize and to delineate the multi-layered
      hippocampal structure ex vivo in rat brains. We optimized a volumic three
      dimensional T2 Rapid Acquisition Relaxation Enhancement (RARE) sequence and
      quantified the volume of the hippocampus and one of its thinnest layers, the
      stratum granulare of the dentate gyrus. Additionally, we tested passive staining
      by gadolinium with the aim of decreasing the acquisition time and increasing
      image contrast. Using appropriated settings, six discrete layers were
      differentiated within the hippocampus in rats. In the hippocampus proper or
      Ammon's Horn (AH): the stratum oriens, the stratum pyramidale of, the stratum
      radiatum, and the stratum lacunosum moleculare of the CA1 were differentiated. In
      the dentate gyrus: the stratum moleculare and the stratum granulare layer were
      seen distinctly. Passive staining of one brain with gadolinium decreased the
      acquisition time by four and improved the differentiation between the layers. A
      conventional sequence optimized on a 7T MRI with a standard receiver surface coil
      will allow us to study structural layers (signal and volume) of hippocampus in
      various rat models of neuropathology (anxiety, epilepsia, neurodegeneration). 

PMID- 24086699
TI  - MicroRNA-212 post-transcriptionally regulates oocyte-specific basic-helix-loop
      helix transcription factor, factor in the germline alpha (FIGLA), during bovine
      early embryogenesis.
AB  - Factor in the germline alpha (FIGLA) is an oocyte-specific basic helix-loop-helix
      transcription factor essential for primordial follicle formation and expression
      of many genes required for folliculogenesis, fertilization and early embryonic
      survival. Here we report the characterization of bovine FIGLA gene and its
      regulation during early embryogenesis. Bovine FIGLA mRNA expression is restricted
      to gonads and is detected in fetal ovaries harvested as early as 90 days of
      gestation. FIGLA mRNA and protein are abundant in germinal vesicle and metaphase
      II stage oocytes, as well as in embryos from pronuclear to eight-cell stage but
      barely detectable at morula and blastocyst stages, suggesting that FIGLA might be
      a maternal effect gene. Recent studies in zebrafish and mice have highlighted the
      importance of non-coding small RNAs (microRNAs) as key regulatory molecules
      targeting maternal mRNAs for degradation during embryonic development. We
      hypothesized that FIGLA, as a maternal transcript, is regulated by microRNAs
      during early embryogenesis. Computational predictions identified a potential
      microRNA recognition element (MRE) for miR-212 in the 3' UTR of the bovine FIGLA
      mRNA. Bovine miR-212 is expressed in oocytes and tends to increase in four-cell
      and eight-cell stage embryos followed by a decline at morula and blastocyst
      stages. Transient transfection and reporter assays revealed that miR-212
      represses the expression of FIGLA in a MRE dependent manner. In addition, ectopic
      expression of miR-212 mimic in bovine early embryos dramatically reduced the
      expression of FIGLA protein. Collectively, our results demonstrate that FIGLA is
      temporally regulated during bovine early embryogenesis and miR-212 is an
      important negative regulator of FIGLA during the maternal to zygotic transition
      in bovine embryos. 

PMID- 24086701
TI  - Therapeutic potential of the translation inhibitor silvestrol in hepatocellular
      cancer.
AB  - BACKGROUND & AIMS: Although hepatocellular cancers (HCC) frequently arise in the
      setting of fibrosis and a hepatic regenerative response requiring new cell
      growth, therapeutic strategies for these cancers have not targeted protein
      synthesis. Silvestrol, a rocaglate isolated from Aglaiafoveolata, can inhibit
      protein synthesis by modulating the initiation of translation through the
      eukaryotic initiation factor 4A. In this study, we evaluated the therapeutic
      efficacy of silvestrol for HCC. METHODS: The efficacy of silvestrol was examined
      using human HCC cells in vitro using an orthotopic tumor cell xenograft model in
      a fibrotic liver. The impact of silvestrol on the liver was assessed in vivo in
      wild-type mice. RESULTS: Silvestrol inhibited cell growth with an IC50 of 12.5-86
      nM in four different HCC cell lines. In vitro, silvestrol increased apoptosis and
      caspase 3/7 activity accompanied by loss of mitochondrial membrane potential and
      decreased expression of Mcl-1 and Bcl-xL. A synergistic effect was observed when
      silvestrol was combined with other therapeutic agents, with a dose-reduction
      index of 3.42-fold with sorafenib and 1.75-fold with rapamycin at a fractional
      effect of 0.5. In vivo, an antitumor effect was observed with 0.4 mg/kg
      silvestrol compared to controls after one week, and survival of tumor-bearing
      mice was improved with a median survival time of 42 and 28 days in the silvestrol
      and control groups, respectively. The effect on survival was not observed in
      orthotopic xenografts in non-fibrotic livers. Silvestrol treatment in vivo did
      not alter liver structure. CONCLUSIONS: These data identify silvestrol as a
      novel, structurally unique drug with potent anticancer activity for HCC and
      support the potential value of targeting initiation of translation in the
      treatment of HCC.

PMID- 24086702
TI  - The origin of biased sequence depth in sequence-independent nucleic acid
      amplification and optimization for efficient massive parallel sequencing.
AB  - Sequence Independent Single Primer Amplification is one of the most widely used
      random amplification approaches in virology for sequencing template preparation.
      This technique relies on oligonucleotides consisting of a 3' random part used to
      prime complementary DNA synthesis and a 5' defined tag sequence for subsequent
      amplification. Recently, this amplification method was combined with next
      generation sequencing to obtain viral sequences. However, these studies showed a
      biased distribution of the resulting sequence reads over the analyzed genomes.
      The aim of this study was to elucidate the mechanisms that lead to biased
      sequence depth when using random amplification. Avian paramyxovirus type 8 was
      used as a model RNA virus to investigate these mechanisms. We showed, based on in
      silico analysis of the sequence depth in relation to GC-content, predicted RNA
      secondary structure and sequence complementarity to the 3' part of the tag
      sequence, that the tag sequence has the main contribution to the observed bias in
      sequence depth. We confirmed this finding experimentally using both fragmented
      and non-fragmented viral RNAs as well as primers differing in random oligomer
      length (6 or 12 nucleotides) and in the sequence of the amplification tag. The
      observed oligonucleotide annealing bias can be reduced by extending the random
      oligomer sequence and by in silico combining sequence data from SISPA experiments
      using different 5' defined tag sequences. These findings contribute to the
      optimization of random nucleic acid amplification protocols that are currently
      required for downstream applications such as viral metagenomics and microarray
      analysis. 

PMID- 24086703
TI  - Trophic hierarchies illuminated via amino acid isotopic analysis.
AB  - Food web ecologists have long sought to characterize the trophic niches of
      animals using stable isotopic analysis. However, distilling trophic position from
      isotopic composition has been difficult, largely because of the variability
      associated with trophic discrimination factors (inter-trophic isotopic
      fractionation and routing). We circumvented much of this variability using
      compound-specific isotopic analysis (CSIA). We examined the (15)N signatures of
      amino acids extracted from organisms reared in pure culture at four discrete
      trophic levels, across two model communities. We calculated the degree of
      enrichment at each trophic level and found there was a consistent trophic
      discrimination factor (~7.60/00). The constancy of the CSIA-derived
      discrimination factor permitted unprecedented accuracy in the measurement of
      animal trophic position. Conversely, trophic position estimates generated via
      bulk-(15)N analysis significantly underestimated trophic position, particularly
      among higher-order consumers. We then examined the trophic hierarchy of a free
      roaming arthropod community, revealing the highest trophic position (5.07) and
      longest food chain ever reported using CSIA. High accuracy in trophic position
      estimation brings trophic function into sharper focus, providing greater
      resolution to the analysis of food webs. 

PMID- 24086704
TI  - Linear and curvilinear relationship between knee range of motion and physical
      functioning in people with knee osteoarthritis: a cross-sectional study.
AB  - BACKGROUND: Knee range of motion (KROM) is associated with the ability to perform
      daily activities in people with knee OA. However, this association is weak,
      possibly through the use of linear analyses. Curvilinear associations appear much
      more relevant, as these allow the determination of relevant clinical thresholds
      in KROM. The goal of this study is to assess the curvilinear association between
      KROM and daily activities (self-reported and observed) in people with knee
      osteoarthritis (OA). METHODS: Demographic, functional and KROM (flexion and
      extension) data were collected from a convenience sample of people with knee OA
      awaiting total knee arthroplasty. Self-reported functioning was measured by use
      of the Knee Osteoarthritis Outcomes Scale and observed functioning with the timed
      up and go and six-minute walk test. The presence of curvilinear relationships
      between KROM and measures of functioning were tested by generalized additive
      modeling, piecewise regression modeling and receiver operated curves. RESULTS:
      Data from 110 participants (mean age +/- standard deviation: 65 +/- 9 and female:
      54%) with knee OA were evaluated. Statistical modeling did not reveal linear nor
      curvilinear associations between KROM and self-reported or observed measures of
      functioning; except for statistical significant associations between reduced knee
      flexion and major difficulties standing (p<=0.01). However, further modeling did
      not provide convincing evidence for relevant clinical associations and
      thresholds. CONCLUSIONS: No clinically relevant relationship between KROM and
      self-reported or observed measures of physical functioning could be established,
      indicating that the limitations in range of motion in the affected knee OA alone
      do not contribute to poorer functional performance.

PMID- 24086705
TI  - Selective cytotoxic action and DNA damage by calcitriol-Cu(II) interaction:
      putative mechanism of cancer prevention.
AB  - BACKGROUND: Vitamin D is known to play an important role in cancer-prevention.
      One of the features associated with the onset of malignancy is the elevation of
      Cu (II) levels. The mode of cancer-prevention mediated by calcitriol, the
      biologically active form of vitamin D, remain largely unknown. METHODS: Using
      exogenously added Cu (II) to stimulate a malignancy like condition in a novel
      cellular system of rabbit calcitriol overloaded lymphocytes, we assessed lipid
      peroxidation, protein carbonylation, DNA damage and consequent apoptosis. Free
      radical mediators were identified using free radical scavengers and the role of
      Cu (II) in the reaction was elucidated using chelators of redox active cellular
      metal ions. RESULTS: Lipid peroxidation and protein carbonylation (markers of
      oxidative stress), consequent DNA fragmentation and apoptosis were observed due
      to calcitriol-Cu (II) interaction. Hydroxyl radicals, hydrogen peroxide and
      superoxide anions mediate oxidative stress produced during this interaction.
      Amongst cellular redox active metals, copper was found to be responsible for this
      reaction. CONCLUSION: This is the first report implicating Cu (II) and calcitriol
      interaction as the cause of selective cytotoxic action of calcitriol against
      malignant cells. We show that this interaction leads to the production of
      oxidative stress due to free radical production and consequent DNA fragmentation,
      which leads to apoptosis. A putative mechanism is presented to explain this
      biological effect.

PMID- 24086706
TI  - Serotyping of Streptococcus pneumoniae based on capsular genes polymorphisms.
AB  - Streptococcus pneumoniae serotype epidemiology is essential since serotype
      replacement is a concern when introducing new polysaccharide-conjugate vaccines.
      A novel PCR-based automated microarray assay was developed to assist in the
      tracking of the serotypes. Autolysin, pneumolysin and eight genes located in the
      capsular operon were amplified using multiplex PCR. This step was followed by a
      tagged fluorescent primer extension step targeting serotype-specific
      polymorphisms. The tagged primers were then hybridized to a microarray. Results
      were exported to an expert system to identify capsular serotypes. The assay was
      validated on 166 cultured S. pneumoniae samples from 63 different serotypes as
      determined by the Quellung method. We show that typing only 12 polymorphisms
      located in the capsular operon allows the identification at the serotype level of
      22 serotypes and the assignation of 24 other serotypes to a subgroup of
      serotypes. Overall, 126 samples (75.9%) were correctly serotyped, 14 were
      assigned to a member of the same serogroup, 8 rare serotypes were erroneously
      serotyped, and 18 gave negative serotyping results. Most of the discrepancies
      involved rare serotypes or serotypes that are difficult to discriminate using a
      DNA-based approach, for example 6A and 6B. The assay was also tested on clinical
      specimens including 43 cerebrospinal fluid samples from patients with meningitis
      and 59 nasopharyngeal aspirates from bacterial pneumonia patients. Overall, 89%
      of specimens positive for pneumolysin were serotyped, demonstrating that this
      method does not require culture to serotype clinical specimens. The assay showed
      no cross-reactivity for 24 relevant bacterial species found in these types of
      samples. The limit of detection for serotyping and S. pneumoniae detection was
      100 genome equivalent per reaction. This automated assay is amenable to clinical
      testing and does not require any culturing of the samples. The assay will be
      useful for the evaluation of serotype prevalence changes after new conjugate
      vaccines introduction. 

PMID- 24086707
TI  - Synergistic effect of various virulence factors leading to high toxicity of
      environmental V. cholerae non-O1/ non-O139 isolates lacking ctx gene :
      comparative study with clinical strains.
AB  - BACKGROUND: Vibrio cholerae non-O1/ non-O139 serogroups have been reported to
      cause sporadic diarrhoea in humans. Cholera toxins have been mostly implicated
      for hypersecretion of ions and water into the small intestine. Though most of the
      V. cholerae non-O1/ non-O139 strains lack these cholera toxins, several other
      innate virulence factors contribute towards their pathogenicity. The
      environmental isolates may thus act as reservoirs for potential spreading of
      these virulence genes in the natural environment which may cause the emergence of
      epidemic-causing organisms. RESULTS: The environmental isolates of vibrios were
      obtained from water samples, zooplanktons and phytoplanktons, from a village pond
      in Gandhinagar, Gujarat, India. They were confirmed as Vibrio cholerae non-O1/
      non-O139 using standard biochemical and serotyping tests. PCR experiments
      revealed that the isolates lacked ctxA, ctxB, tcpA, zot and ace genes whereas
      other pathogenicity genes like toxR, rtxC, hlyA, hapA and prtV were detected in
      these isolates. Compared with epidemic strain V. cholerae O1 El Tor N16961,
      culture supernatants from most of these isolates caused higher cytotoxicity to
      HT29 cells and higher hemolytic, hemagglutinin and protease activities. In rabbit
      ileal loop assays, the environmental isolates showed only 2-4 folds lesser fluid
      accumulation in comparison to N16961 and a V. cholerae clinical isolate IDH02365
      of 2009. Pulsed Field Gel electrophoresis and Random amplification of Polymorphic
      DNA indicated that these isolates showed considerable diversity and did not share
      the same clonal lineage even though they were derived from the same water source.
      All the isolates showed resistance to one or more antibiotics. CONCLUSION: Though
      these environmental isolates lacked the cholera toxins, they seem to have adopted
      other survival strategies by optimally utilising a diverse array of several other
      toxins. The current findings indicate the possibility that these isolates could
      cause some gastroenteric inflammation when ingested and may serve as progenitors
      for overt disease-causing organisms.

PMID- 24086708
TI  - Depletion of the adaptor protein NCK increases UV-induced p53 phosphorylation and
      promotes apoptosis.
AB  - The cellular response to DNA damage requires the coordination of many proteins
      involved in diverse molecular processes. Discrete molecular pathways are becoming
      increasingly well understood, but the interconnectivity and coordination of
      multiple pathways remains less clear. We now show that NCK, an adapter protein
      involved in cytoskeletal responses to tyrosine kinase receptor signaling,
      accumulates in the nucleus in response to DNA damage and this translocation can
      be blocked by specific inhibition of the ATR protein kinase. Strikingly, HeLa
      cells depleted of NCK undergo apoptosis shortly after UV irradiation, as
      monitored by caspase-3 cleavage and PARP cleavage. This rapid, hyperactive
      apoptosis in NCK depleted cells might be p53 dependent, because loss of NCK also
      increased UV-induced p53 phosphorylation. Importantly, depletion of SOCS7, which
      is necessary for NCK nuclear translocation, phenocopies NCK depletion, indicating
      the nuclear accumulation of NCK is responsible for these molecular events. There
      are two NCK isoforms that have mostly redundant functions, and although NCK2
      appears to have a greater contribution, depletion of NCK1 or NCK2, led to
      increased p53 phosphorylation and early apoptosis after UV exposure. These data
      reveal a novel function for NCK in regulating p53 phosphorylation and apoptosis,
      and provide evidence for interconnectedness of growth factor signaling proteins
      and the DNA damage response. 

PMID- 24086709
TI  - Microsatellite development and first population size estimates for the
      groundwater isopod Proasellus walteri.
AB  - Effective population size (N e) is one of the most important parameters in,
      ecology, evolutionary and conservation biology; however, few studies of N e in
      surface freshwater organisms have been published to date. Even fewer studies have
      been carried out in groundwater organisms, although their evolution has long been
      considered to be particularly constrained by small N e. In this study, we
      estimated the contemporary effective population size of the obligate groundwater
      isopod: Proaselluswalteri (Chappuis, 1948). To this end, a genomic library was
      enriched for microsatellite motifs and sequenced using 454 GS-FLX technology. A
      total of 54,593 reads were assembled in 10,346 contigs or singlets, of which 245
      contained candidate microsatellite sequences with suitable priming sites. Ninety
      six loci were tested for amplification, polymorphism and multiplexing properties,
      of which seven were finally selected for N e estimation. Linkage disequilibrium
      and approximate Bayesian computation methods revealed that N e in this small
      interstitial groundwater isopod could reach large sizes (> 585 individuals). Our
      results suggest that environmental conditions in groundwater, while often
      referred to as extreme, are not necessarily associated with small N e. 

PMID- 24086710
TI  - Whatever works: a systematic user-centered training protocol to optimize brain
      computer interfacing individually.
AB  - This study implemented a systematic user-centered training protocol for a 4-class
      brain-computer interface (BCI). The goal was to optimize the BCI individually in
      order to achieve high performance within few sessions for all users. Eight able
      bodied volunteers, who were initially naive to the use of a BCI, participated in
      10 sessions over a period of about 5 weeks. In an initial screening session,
      users were asked to perform the following seven mental tasks while multi-channel
      EEG was recorded: mental rotation, word association, auditory imagery, mental
      subtraction, spatial navigation, motor imagery of the left hand and motor imagery
      of both feet. Out of these seven mental tasks, the best 4-class combination as
      well as most reactive frequency band (between 8-30 Hz) was selected individually
      for online control. Classification was based on common spatial patterns and
      Fisher's linear discriminant analysis. The number and time of classifier updates
      varied individually. Selection speed was increased by reducing trial length. To
      minimize differences in brain activity between sessions with and without
      feedback, sham feedback was provided in the screening and calibration runs in
      which usually no real-time feedback is shown. Selected task combinations and
      frequency ranges differed between users. The tasks that were included in the 4
      class combination most often were (1) motor imagery of the left hand (2), one
      brain-teaser task (word association or mental subtraction) (3), mental rotation
      task and (4) one more dynamic imagery task (auditory imagery, spatial navigation,
      imagery of the feet). Participants achieved mean performances over sessions of 44
      84% and peak performances in single-sessions of 58-93% in this user-centered 4
      class BCI protocol. This protocol is highly adjustable to individual users and
      thus could increase the percentage of users who can gain and maintain BCI
      control. A high priority for future work is to examine this protocol with
      severely disabled users. 

PMID- 24086711
TI  - Significance of mannose-binding lectin deficiency and nucleotide-binding
      oligomerization domain 2 polymorphisms in Staphylococcus aureus bloodstream
      infections: a case-control study.
AB  - BACKGROUND: Pathways coordinated by innate pattern recognition receptors like
      mannose-binding lectin (MBL) and nucleotide-binding oligomerization domain 2
      (NOD2) are among the first immune responses to Staphylococcus aureus (S. aureus)
      bloodstream infections (BSI) in animal models, but human data are limited. Here,
      we investigated the role of MBL deficiency and NOD2 mutations in the
      predisposition to and severity of S. aureus BSI. PATIENTS AND METHODS: A matched
      case-control study was undertaken involving 70 patients with S. aureus BSI and 70
      age- and sex-matched hospitalized controls. MBL levels, MBL2 and NOD2
      polymorphisms were analyzed. RESULTS: After adjusting for potential confounders,
      MBL deficiency (<0.5 ug/ml) was found less frequently in cases than controls (26
      vs. 41%, OR 0.4, 95% confidence interval (CI) 0.20-0.95, p=0.04) as were low
      producing MBL genotypes (11 vs. 23%, OR 0.2, 95% CI 0.08-0.75, p=0.01), whereas
      NOD2 polymorphisms were similarly distributed. Cases with NOD2 polymorphisms had
      less organ dysfunction as shown by a lower SOFA score (median 2.5 vs. 4.5,
      p=0.02), whereas only severe MBL deficiency (<0.1 ug/ml) was associated with life
      threatening S. aureus BSI (OR 5.6, 95% CI 1.25-24.85, p=0.02). CONCLUSIONS:
      Contrary to animal model data, our study suggests MBL deficiency may confer
      protection against acquiring S. aureus BSI. NOD2 mutations were less frequently
      associated with multi-organ dysfunction. Further human studies of the innate
      immune response in S. aureus BSI are needed to identify suitable host targets in
      sepsis treatment.

PMID- 24086712
TI  - Integrated proteomic and metabolic analysis of breast cancer progression.
AB  - One of the most persistent hallmarks of cancer biology is the preference of tumor
      cells to derive energy through glycolysis as opposed to the more efficient
      process of oxidative phosphorylation (OXPHOS). However, little is known about the
      molecular cascades by which oncogenic pathways bring about this metabolic switch.
      We carried out a quantitative proteomic and metabolic analysis of the MCF10A
      derived cell line model of breast cancer progression that includes parental cells
      and derivatives representing three different tumor grades of Ras-driven cancer
      with a common genetic background. A SILAC (Stable Isotope Labeling by Amino acids
      in Cell culture) labeling strategy was used to quantify protein expression in
      conjunction with subcellular fractionation to measure dynamic subcellular
      localization in the nucleus, cytosol and mitochondria. Protein expression and
      localization across cell lines were compared to cellular metabolic rates as a
      measure of oxidative phosphorylation (OXPHOS), glycolysis and cellular ATP.
      Investigation of the metabolic capacity of the four cell lines revealed that
      cellular OXPHOS decreased with breast cancer progression independently of
      mitochondrial copy number or electron transport chain protein expression.
      Furthermore, glycolytic lactate secretion did not increase in accordance with
      cancer progression and decreasing OXPHOS capacity. However, the relative
      expression and subcellular enrichment of enzymes critical to lactate and pyruvate
      metabolism supported the observed extracellular acidification profiles. This
      analysis of metabolic dysfunction in cancer progression integrated with global
      protein expression and subcellular localization is a novel and useful technique
      for determining organelle-specific roles of proteins in disease. 

PMID- 24086713
TI  - Phenotypic diversity of multicellular filamentation in oral Streptococci.
AB  - Filamentous multicellular bacteria are among the most ancient multicellular
      organisms. They inhabit a great variety of environments and are present in the
      human body, including the oral cavity. Beside the selective advantages related to
      the larger size achieved through filamentation, the development of multicellular
      bacteria can be also driven by simple ecological factors such as birth and death
      rates at the cellular level. In order to extend earlier results obtained in
      aquatic species, we investigate the filamentation process of four different
      strains of oral streptococci, namely S. mutans, S. salivarius, S. oralis and S.
      anginosus. The results indicate differences in the capacities of different
      streptococcus species to form filaments, manifested in terms of length and the
      time-scale of filament elongation. The filamentation pattern of these oral
      streptococci resembles that of aquatic bacteria, whereby filaments reach a peak
      length during exponential growth and become short when the population reaches a
      steady state. Hence, this study validates that multicellularity can be an
      emergent property of filamentous bacteria of different ecological niches, and
      that phenotypic differences in filamentation can occur within species of the same
      genus, in this case oral streptococci. Moreover, given the role that specific
      oral streptococci can play in the etiology of oral diseases, these results can
      possibly open new perspectives in the study of the virulence properties of these
      species. 

PMID- 24086714
TI  - Thioredoxin1 downregulates oxidized low-density lipoprotein-induced adhesion
      molecule expression via Smad3 protein.
AB  - Atherosclerosis is a chronic inflammation disease that is initiated by
      endothelial cell injury. Oxidized low-density lipoprotein (ox-LDL) is directly
      associated with chronic vascular inflammation. To understand whether thioredoxin1
      (Trx1) participates in an antiinflammatory defense mechanism in atherosclerosis,
      we investigated the effect of Trx1 on the expression of two adhesion molecules,
      vascular cell adhesion molecule-1 (VCAM-1) and intercellular adhesion molecule-1
      (ICAM-1), in human umbilical vein endothelial cells (HUVECs). Thioredoxin1 and
      dominant-negative mutant thioredoxin1 (TD) were transiently overexpressed using
      adenovirus vector gene transfer. Our data showed that Trx1 overexpression
      suppressed ox-LDL-induced adhesion molecule expression in HUVECs. The
      overexpression of Trx1 promoted ox-LDL-induced Smad3 phosphorylation and nuclear
      translocation. A co-immunoprecipitation assay indicated that Smad3 continued to
      interact with Trx1 with or without ox-LDL stimulation. These results suggest that
      Trx1 inherently suppresses VCAM-1 and ICAM-1 expression in vascular endothelia
      and may prevent the initiation of atherosclerosis by attenuating adhesion
      molecule expression. The enhancement of Smad3 phosphorylation and nuclear
      expression appears to be primarily responsible for the Trx1-induced
      downregulation of adhesion molecules. 

PMID- 24086715
TI  - Transient population dynamics of mosquitoes during sterile male releases:
      modelling mating behaviour and perturbations of life history parameters.
AB  - The release of genetically-modified or sterile male mosquitoes offers a promising
      form of mosquito-transmitted pathogen control, but the insights derived from our
      understanding of male mosquito behaviour have not fully been incorporated into
      the design of such genetic control or sterile-male release methods. The
      importance of aspects of male life history and mating behaviour for sterile-male
      release programmes were investigated by projecting a stage-structured matrix
      model over time. An elasticity analysis of transient dynamics during sterile-male
      releases was performed to provide insight on which vector control methods are
      likely to be most synergistic. The results suggest that high mating
      competitiveness and mortality costs of released males are required before the
      sterile-release method becomes ineffective. Additionally, if released males
      suffer a mortality cost, older males should be released due to their increased
      mating capacity. If released males are of a homogenous size and size-assortative
      mating occurs in nature, this can lead to an increase in the abundance of large
      females and reduce the efficacy of the population-suppression effort. At a high
      level of size-assortative mating, the disease transmission potential of the
      vector population increases due to male releases, arguing for the release of a
      heterogeneously-sized male population. The female population was most sensitive
      to perturbations of density-dependent components of larval mortality and female
      survivorship and fecundity. These findings suggest source reduction might be a
      particularly effective complement to mosquito control based on the sterile insect
      technique (SIT). In order for SIT to realize its potential as a key component of
      an integrated vector-management strategy to control mosquito-transmitted
      pathogens, programme design of sterile-male release programmes must account for
      the ecology, behaviour and life history of mosquitoes. The model used here takes
      a step in this direction and can easily be modified to investigate additional
      aspects of mosquito behaviour or species-specific ecology. 

PMID- 24086716
TI  - Molecular engineering of a fluorescent bioprobe for sensitive and selective
      detection of amphibole asbestos.
AB  - Fluorescence microscopy-based affinity assay could enable highly sensitive and
      selective detection of airborne asbestos, an inorganic environmental pollutant
      that can cause mesothelioma and lung cancer. We have selected an Escherichia coli
      histone-like nucleoid structuring protein, H-NS, as a promising candidate for an
      amphibole asbestos bioprobe. H-NS has high affinity to amphibole asbestos, but
      also binds to an increasingly common asbestos substitute, wollastonite. To
      develop a highly specific Bioprobe for amphibole asbestos, we first identified a
      specific but low-affinity amosite-binding sequence by slicing H-NS into several
      fragments. Second, we constructed a streptavidin tetramer complex displaying four
      amosite-binding fragments, resulting in the 250-fold increase in the probe
      affinity as compared to the single fragment. The tetramer probe had sufficient
      affinity and specificity for detecting all the five types of asbestos in the
      amphibole group, and could be used to distinguish them from wollastonite. In
      order to clarify the binding mechanism and identify the amino acid residues
      contributing to the probe's affinity to amosite fibers, we constructed a number
      of shorter and substituted peptides. We found that the probable binding mechanism
      is electrostatic interaction, with positively charged side chains of lysine
      residues being primarily responsible for the probe's affinity to asbestos. 

PMID- 24086717
TI  - NR4A2 is regulated by gastrin and influences cellular responses of gastric
      adenocarcinoma cells.
AB  - The peptide hormone gastrin is known to play a role in differentiation, growth
      and apoptosis of cells in the gastric mucosa. In this study we demonstrate that
      gastrin induces Nuclear Receptor 4A2 (NR4A2) expression in the adenocarcinoma
      cell lines AR42J and AGS-GR, which both possess the gastrin/CCK2 receptor. In
      vivo, NR4A2 is strongly expressed in the gastrin responsive neuroendocrine ECL
      cells in normal mucosa, whereas gastric adenocarcinoma tissue reveals a more
      diffuse and variable expression in tumor cells. We show that NR4A2 is a primary
      early transient gastrin induced gene in adenocarcinoma cell lines, and that NR4A2
      expression is negatively regulated by inducible cAMP early repressor (ICER) and
      zinc finger protein 36, C3H1 type-like 1 (Zfp36l1), suggesting that these gastrin
      regulated proteins exert a negative feedback control of NR4A2 activated
      responses. FRAP analyses indicate that gastrin also modifies the nucleus-cytosol
      shuttling of NR4A2, with more NR4A2 localized to cytoplasm upon gastrin
      treatment. Knock-down experiments with siRNA targeting NR4A2 increase migration
      of gastrin treated adenocarcinoma AGS-GR cells, while ectopically expressed NR4A2
      increases apoptosis and hampers gastrin induced invasion, indicating a tumor
      suppressor function of NR4A2. Collectively, our results uncover a role of NR4A2
      in gastric adenocarcinoma cells, and suggest that both the level and the
      localization of NR4A2 protein are of importance regarding the cellular responses
      of these cells. 

PMID- 24086718
TI  - The N-terminal region of the human autophagy protein ATG16L1 contains a domain
      that folds into a helical structure consistent with formation of a coiled-coil.
AB  - Autophagy is a fundamental cellular process required for organelle degradation
      and removal of invasive pathogens. Autophagosome formation involves the
      recruitment of, and interaction between, multiple proteins produced from
      autophagy-related (ATG) genes. One of the key complexes in autophagosome
      formation is the ATG12-ATG5-ATG16L1 complex. ATG16L1 functions as a molecular
      scaffold mediating protein-protein interactions necessary for formation of the
      autophagosome in response to both classical and pathogen-related autophagy
      stimuli. The coiled-coil domain of the yeast ortholog, ATG16, exists as a
      homodimer both in solution and in the crystal form. The yeast and human orthologs
      show poor sequence identity. Here we have sought to determine the minimal
      boundaries of the human ATG16L1 coiled-coil domain and ascertain its oligomeric
      status in solution. Using a range of biochemical and biophysical techniques we
      show that the secondary structure of the human ATG16L1 coiled-coil has the
      expected helical composition and that the domain forms a homodimer in solution.
      We also observe extensive sequence conservation across vertebrates providing
      strong support for the crucial functional role of the ATG16L1 coiled-coil. 

PMID- 24086719
TI  - Low pulmonary function in individuals with impaired fasting glucose: the 2007
      2009 Korea national health and nutrition examination survey.
AB  - OBJECTIVE: To investigate the association between fasting plasma glucose level
      and pulmonary function. RESEARCH DESIGN AND METHODS: Nutritional information,
      pulmonary function data, and laboratory test data from 9,223 subjects from the
      fourth Korea National Health and Nutrition Examination Survey were examined. The
      participants were divided into five groups according to fasting plasma glucose
      (FPG) level: normal fasting glucose (NFG)1, FPG <90 mg/dl; NFG2, FPG 90-99 mg/dl;
      impaired fasting glucose (IFG)1: FPG 100-109 mg/dl; IFG2, FPG 110-125 mg/dl; and
      diabetes, FPG >=126 mg/dl and/or current anti-diabetes medications. RESULTS:
      After adjustment for several variables, the percentage of predicted forced vital
      capacity(FVC%) decreased with increasing fasting plasma glucose level in both
      sexes[men: (mean +/- SEM) 92.0+/-0.3 in NFG1; 91.9+/-0.3 in NFG2; 92.0+/-0.4 in
      IFG1; 90.2+/-0.7 in IFG2; and 89.9+/-0.5 in diabetes, P = 0.004; women: 93.7+/
      0.3 in NFG1; 93.7+/-0.3 in NFG2; 93.1+/-0.5 in IFG1; 91.1+/-0.9 in IFG2; and
      90.7+/-0.6 in diabetes, P<0.001]. A logistic regression analysis found that IFG2
      and diabetes were independently associated with the lowest quintile of predicted
      FVC% (IFG2: odds ratio [95%CI], 1.50 [1.18-1.89], P = 0.001; diabetes: 1.56 [1.30
      1.88], P<0.001) using NFG1 as a control. CONCLUSIONS: The current data suggest
      that forced vital capacity may begin to decrease in the higher range of IFG.

PMID- 24086720
TI  - Peroxisome protein transportation affects metabolism of branched-chain fatty
      acids that critically impact growth and development of C. elegans.
AB  - The impact of specific lipid molecules, including fatty acid variants, on
      cellular and developmental regulation is an important research subject that
      remains under studied. Monomethyl branched-chain fatty acids (mmBCFAs) are
      commonly present in multiple organisms including mammals, however our
      understanding of mmBCFA functions is very limited. C. elegans has been the
      premier model system to study the functions of mmBCFAs and their derived lipids,
      as mmBCFAs have been shown to play essential roles in post-embryonic development
      in this organism. To understand more about the metabolism of mmBCFAs in C.
      elegans, we performed a genetic screen for suppressors of the L1 developmental
      arrest phenotype caused by mmBCFA depletion. Extensive characterization of one
      suppressor mutation identified prx-5, which encodes an ortholog of the human
      receptor for the type-1 peroxisomal targeting signal protein. Our study showed
      that inactivating prx-5 function compromised the peroxisome protein import,
      resulting in an increased level of branched-chain fatty acid C17ISO in animals
      lacking normal mmBCFA synthesis, thereby restoring wild-type growth and
      development. This work reveals a novel connection between peroxisomal functions
      and mmBCFA metabolism. 

PMID- 24086722
TI  - Interleukin 15 primes natural killer cells to kill via NKG2D and cPLA2 and this
      pathway is active in psoriatic arthritis.
AB  - NK cells are large granular lymphocytes that form a critical component of the
      innate immune system, whose functions include the killing of cells expressing
      stress-induced molecules. It is increasingly accepted that despite being
      considered prototypical effector cells, NK cells require signals to reach their
      full cytotoxic potential. We previously showed that IL-15 is capable of arming
      CD8 effector T cells to kill independently of their TCR via NKG2D in a cPLA2
      dependent process. As NK cells also express NKG2D, we wanted to investigate
      whether this pathway functioned in an analogous manner and if resting NK cells
      could be primed to the effector phase by IL-15. Furthermore, to establish
      relevance to human disease we studied a possible role for this pathway in the
      pathogenesis of psoriatic arthritis, since there are aspects of this disease that
      suggest a potential effector role for the innate immune system. We found that PsA
      patients had upregulated IL-15 and MIC in their affected synovial tissues, and
      that this unique inflammatory environment enabled NK cell activation and killing
      via NKG2D and cPLA2. Moreover, we were able to reproduce the phenotype of joint
      NK cells from blood NK cells by incubating them with IL-15. Altogether, these
      findings suggest a destructive role for NK cells when activated by environmental
      stress signals during the pathogenesis of PsA and demonstrate that IL-15 is
      capable of priming resting NK cells in tissues to the effector phase. 

PMID- 24086721
TI  - Comparative genomic analysis of multi-subunit tethering complexes demonstrates an
      ancient pan-eukaryotic complement and sculpting in Apicomplexa.
AB  - Apicomplexa are obligate intracellular parasites that cause tremendous disease
      burden world-wide. They utilize a set of specialized secretory organelles in
      their invasive process that require delivery of components for their biogenesis
      and function, yet the precise mechanisms underpinning such processes remain
      unclear. One set of potentially important components is the multi-subunit
      tethering complexes (MTCs), factors increasingly implicated in all aspects of
      vesicle-target interactions. Prompted by the results of previous studies
      indicating a loss of membrane trafficking factors in Apicomplexa, we undertook a
      bioinformatic analysis of MTC conservation. Building on knowledge of the ancient
      presence of most MTC proteins, we demonstrate the near complete retention of MTCs
      in the newly available genomes for Guillardiatheta and Bigelowiellanatans. The
      latter is a key taxonomic sampling point as a basal sister taxa to the group
      including Apicomplexa. We also demonstrate an ancient origin of the CORVET
      complex subunits Vps8 and Vps3, as well as the TRAPPII subunit Tca17. Having
      established that the lineage leading to Apicomplexa did at one point possess the
      complete eukaryotic complement of MTC components, we undertook a deeper taxonomic
      investigation in twelve apicomplexan genomes. We observed excellent conservation
      of the VpsC core of the HOPS and CORVET complexes, as well as the core TRAPP
      subunits, but sparse conservation of TRAPPII, COG, Dsl1, and HOPS/CORVET-specific
      subunits. However, those subunits that we did identify appear to be expressed
      with similar patterns to the fully conserved MTC proteins, suggesting that they
      may function as minimal complexes or with analogous partners. Strikingly, we
      failed to identify any subunits of the exocyst complex in all twelve apicomplexan
      genomes, as well as the dinoflagellate Perkinsus marinus. Overall, we demonstrate
      reduction of MTCs in Apicomplexa and their ancestors, consistent with
      modification during, and possibly pre-dating, the move from free-living marine
      algae to deadly human parasites. 

PMID- 24086723
TI  - Incidence of metabolic syndrome over 9 years follow-up; the importance of sex
      differences in the role of insulin resistance and other risk factors.
AB  - To determine, the predictors of incident metabolic syndrome (MetS) in a community
      based cohort of West Asians, during a mean follow-up of 9.3 years, a sample of
      2858 non-MetS Iranian adults aged >= 20 years were examined at baseline and
      followed at three year intervals during three consecutive phases. The MetS was
      defined using the joint interim statement. Cox proportional hazard regression was
      used to determine the independent variables associated with incident MetS.
      Overall, 1117 new cases MetS were identified resulting in an incidence rate of
      550.9/10000 person years (95% CI: 519.5-584.2). The corresponding incidence rates
      among women and men were 433.5/10000 person years (95% CI: 398.8-471.2) and
      749.2/10000 person years (95% CI: 689.9-813.5), respectively. Baseline-adjusted
      predictors of developing MetS included all of the MetS components, being
      overweight or obese in both gender, and family history of diabetes and age only
      in women. There were significant effect modifications of gender on age (P<0.001),
      high blood pressure (0.026), high waist circumference (P<0001) and obesity
      categories (all P <= 0.01) in multivariate analysis. After considering HOMA-IR in
      the model, among women, all of the MetS predictors as well as those with HOMA-IR
      >= 2.23 showed a significant risk for incident MetS [HR: 1.63 (1.16-2.28)];
      however, among men all the MetS components (WC was marginally significant) as
      well as the fourth quartile of HOMA-IR [HR: 1.50 (1.03-2.17)] and being
      overweight showed a significant risk. Finally, in the pooled analysis, we showed
      that female gender had lower risk for incident MetS than male [HR: 0.58 (0.47
      0.70)]. In the Iranian population, high incidence of MetS, especially among men,
      was shown. Our findings confirmed that sex- specific risk predictors should be
      considered in primary prevention for incident MetS. 

PMID- 24086724
TI  - Low molecular weight protein tyrosine phosphatase isoforms regulate breast cancer
      cells migration through a RhoA dependent mechanism.
AB  - Low molecular weight protein tyrosine phosphatase (LMW-PTP) has been associated
      with cell proliferation control through dephosphorylation and inactivation of
      growth factor receptors such as PDGF-R and EphA2, and with cellular adhesion and
      migration through p190RhoGap and RhoA. We aim to clarify the role of two main LMW
      PTP isoforms in breast cancer tumorigenesis. We used a siRNA-mediated loss-of
      function in MDA-MB-435 breast cancer cell line to study the role of the two main
      LMW-PTP isoforms, fast and slow, in breast cancer tumorigenesis and migration.
      Our results show that the siRNAs directed against total LMW-PTP and LMW-PTP slow
      isoform enhanced cell motility in an invasive breast cancer cell line, MDA-MB
      435, with no changes in the proliferation and invasive potential of cells. The
      total LMW-PTP knockdown caused a more pronounced increase of cell migration.
      Suppression of total LMW-PTP decreased RhoA activation and suppression of the LMW
      PTP slow isoform caused a small but significant increase in RhoA activation. We
      propose that the increase or decrease in RhoA activation induces changes in
      stress fibers formation and consequently alter the adhesive and migratory
      potential of cells. These findings suggest that the two main isoforms of LMW-PTP
      may act differentially, with the fast isoform having a more prominent role in
      tumor cell migration. In addition, our results highlight functional specificity
      among LMW-PTP isoforms, suggesting hitherto unknown roles for these proteins in
      breast cancer biology. Novel therapeutic approaches targeting LMW-PTP,
      considering the expression of these two isoforms and not LMW-PTP as a whole,
      should be investigated. 

PMID- 24086725
TI  - Analysis of transduction efficiency, tropism and axonal transport of AAV
      serotypes 1, 2, 5, 6, 8 and 9 in the mouse brain.
AB  - Recombinant Adeno-associated virus vectors (rAAV) are widely used for gene
      delivery and multiple naturally occurring serotypes have been harnessed to target
      cells in different tissues and organs including the brain. Here, we provide a
      detailed and quantitative analysis of the transduction profiles of rAAV vectors
      based on six of the most commonly used serotypes (AAV1, AAV2, AAV5, AAV6, AAV8,
      AAV9) that allows systematic comparison and selection of the optimal vector for a
      specific application. In our studies we observed marked differences among
      serotypes in the efficiency to transduce three different brain regions namely the
      striatum, hippocampus and neocortex of the mouse. Despite the fact that the
      analyzed serotypes have the general ability to transduce all major cell types in
      the brain (neurons, microglia, astrocytes and oligodendrocytes), the expression
      level of a reporter gene driven from a ubiquitous promoter varies significantly
      for specific cell type / serotype combinations. For example, rAAV8 is
      particularly efficient to drive transgene expression in astrocytes while rAAV9
      appears well suited for the transduction of cortical neurons. Interestingly, we
      demonstrate selective retrograde transport of rAAV5 along axons projecting from
      the ventral part of the entorhinal cortex to the dentate gyrus. Furthermore, we
      show that self-complementing rAAV can be used to significantly decrease the time
      required for the onset of transgene expression in the mouse brain. 

PMID- 24086726
TI  - Replication study for the association of 9 East Asian GWAS-derived loci with
      susceptibility to type 2 diabetes in a Japanese population.
AB  - AIMS: East Asian genome-wide association studies (GWAS) for type 2 diabetes
      identified 8 loci with genome-wide significance, and 2 loci with a borderline
      association. However, the associations of these loci except MAEA locus with type
      2 diabetes have not been evaluated in independent East Asian cohorts. We
      performed a replication study to investigate the association of these
      susceptibility loci with type 2 diabetes in an independent Japanese population.
      METHODS: We genotyped 7,379 Japanese participants (5,315 type 2 diabetes and
      2,064 controls) for each of the 9 single nucleotide polymorphisms (SNPs),
      rs7041847 in GLIS3, rs6017317 in FITM2-R3HDML-HNF4A, rs6467136 near GCCI-PAX4,
      rs831571 near PSMD6, rs9470794 in ZFAND3, rs3786897 in PEPD, rs1535500 in KCNK16,
      rs16955379 in CMIP, and rs17797882 near WWOX. Because the sample size in this
      study was not sufficient to replicate single SNP associations, we constructed a
      genetic risk score (GRS) by summing a number of risk alleles of the 9 SNPs, and
      examined the association of the GRS with type 2 diabetes using logistic
      regression analysis. RESULTS: With the exception of rs1535500 in KCNK16, all SNPs
      had the same direction of effect (odds ratio [OR]>1.0) as in the original
      reports. The GRS constructed from the 9 SNPs was significantly associated with
      type 2 diabetes in the Japanese population (p = 4.0 * 10(-4), OR = 1.05, 95%
      confidence interval: 1.02-1.09). In quantitative trait analyses, rs16955379 in
      CMIP was nominally associated with a decreased homeostasis model assessment of
      beta-cell function and with increased fasting plasma glucose, but neither the
      individual SNPs nor the GRS showed a significant association with the glycemic
      traits. CONCLUSIONS: These results indicate that 9 loci that were identified in
      the East Asian GWAS meta-analysis have a significant effect on the susceptibility
      to type 2 diabetes in the Japanese population.

PMID- 24086727
TI  - DIRS and Ngaro Retrotransposons in Fungi.
AB  - Retrotransposons with a tyrosine recombinase (YR) have been discovered recently
      and lack thorough annotation in fungi. YR retrotransposons are divided into 3
      groups: DIRS, Ngaro and VIPER (known only from kinetoplastida). We used
      comparative genomics to investigate the evolutionary patterns of retrotransposons
      in the fungal kingdom. The identification of both functional and remnant elements
      provides a unique view on both recent and past transposition activity. Our
      searches covering a wide range of fungal genomes allowed us to identify 2241 YR
      retrotransposons. Based on CLANS clustering of concatenated sequences of the
      reverse transcriptase (RT), RNase H (RH), DNA N-6-adenine-methyltransferase (MT)
      and YR protein domains we propose a revised classification of YR elements
      expanded by two new categories of Ngaro elements. A phylogenetic analysis of 477
      representatives supports this observation and additionally demonstrates that DIRS
      and Ngaro abundance changed independently in Basidiomycota and
      Blastocladiomycota/Mucoromycotina/Kixellomycotina. Interestingly, a single
      remnant Ngaro element could be identified in an Ascomycota genome. Our analysis
      revealed also that 3 Pucciniomycotina taxa, known for their overall mobile
      element abundance and big genome size, encode an elevated number of Ngaro
      retrotransposons. Considering the presence of DIRS elements in all analyzed
      Mucoromycotina, Kickxellomycotina and Blastocladiomycota genomes one might assume
      a common origin of fungal DIRS retrotransposons with a loss in Dicarya. Ngaro
      elements described to date from Opisthokonta, seem to have invaded the common
      ancestor of Agaricomycotina and Pucciniomycotina after Ustilagomycotina
      divergence. Yet, most of analyzed genomes are devoid of YR elements and most
      identified retrotransposons are incomplete. 

PMID- 24086728
TI  - Cordycepin regulates GSK-3beta/beta-catenin signaling in human leukemia cells.
AB  - BACKGROUND: Leukemia stem cells (LSCs) are a limitless cell source for the
      initiation and maintenance of leukemia. Activation of the Wnt/beta-catenin
      pathway is required for the survival and development of LSCs. Therefore,
      targeting beta-catenin is considered a therapeutic strategy for the treatment of
      leukemia. The goal of this study was to explore whether cordycepin, an active
      component of the traditional medicine Cordyceps sinensis, regulates beta-catenin
      expression in leukemia cells. METHODOLOGY AND PRINCIPAL FINDINGS: In this study,
      we found that cordycepin significantly suppressed cell proliferation in all
      malignant cancer cells, including U937, K562, A549, HepG2, SK-Hep1 and MCF7 in a
      dose-dependent manner. However, cordycepin reduced beta-catenin levels in U937,
      K562 and THP1 leukemia cells and had no effect on other solid cancer cells. In
      addition, treatment with cordycepin significantly suppressed leukemia colony
      formation in soft agar assay. Cordycepin enhanced proteasome-dependent
      degradation and inhibited nuclear translocation of beta-catenin in leukemia
      cells. Cordycepin-reduced beta-catenin stability was restored by the addition of
      a pharmacological inhibitor of GSK-3beta, indicating that cordycepin-suppressed
      beta-catenin stability is mediated by the activation of GSK-3beta. Furthermore,
      cordycepin abolished the effect of Wnt3a-induced beta-catenin in leukemia cells.
      In addition, cordycepin-impaired beta-catenin is regulated by Akt activation but
      is not significantly influenced by AMPK or mTOR signal pathways. SIGNIFICANCE:
      Our findings show for the first time that codycepin selectively reduces beta
      catenin stability in leukemia but not in other solid tumor cells. This
      suppressive effect is mediated by regulating GSK-3beta. A synergistic combination
      of cordycepin with other treatments should be used as a novel strategy to
      eradicate leukemia via elimination of LSCs.

PMID- 24086729
TI  - Tropical aquatic Archaea show environment-specific community composition.
AB  - The Archaea domain is ubiquitously distributed and extremely diverse, however,
      environmental factors that shape archaeal community structure are not well known.
      Aquatic environments, including the water column and sediments harbor many new
      uncultured archaeal species from which metabolic and ecological roles remain
      elusive. Some environments are especially neglected in terms of archaeal
      diversity, as is the case of pristine tropical areas. Here we investigate the
      archaeal composition in marine and freshwater systems from Ilha Grande, a South
      Atlantic tropical environment. All sampled habitats showed high archaeal
      diversity. No OTUs were shared between freshwater, marine and mangrove sediment
      samples, yet these environments are interconnected and geographically close,
      indicating environment-specific community structuring. Group II Euryarchaeota was
      the main clade in marine samples, while the new putative phylum Thaumarchaeota
      and LDS/RCV Euryarchaeota dominated freshwaters. Group III Euryarchaeota, a rare
      clade, was also retrieved in reasonable abundance in marine samples. The archaeal
      community from mangrove sediments was composed mainly by members of mesophilic
      Crenarchaeota and by a distinct clade forming a sister-group to Crenarchaeota and
      Thaumarchaeota. Our results show strong environment-specific community
      structuring in tropical aquatic Archaea, as previously seen for Bacteria. 

PMID- 24086730
TI  - Stem cell-like dog placenta cells afford neuroprotection against ischemic stroke
      model via heat shock protein upregulation.
AB  - In this study, we investigated the dog placenta as a viable source of stem cells
      for stroke therapy. Immunocytochemical evaluation of phenotypic markers of dog
      placenta cells (DPCs) cultured in proliferation and differentiation medium
      revealed that DPCs expressed both stem cell and neural cell markers,
      respectively. Co-culture with DPCs afforded neuroprotection of rat primary neural
      cells in a dose-dependent manner against oxygen-glucose deprivation. Subsequent
      in vivo experiments showed that transplantation of DPCs, in particular
      intravenous and intracerebral cell delivery, produced significant behavioral
      recovery and reduced histological deficits in ischemic stroke animals compared to
      those that received intra-arterial delivery of DPCs or control stroke animals.
      Furthermore, both in vitro and in vivo studies implicated elevated expression of
      heat shock protein 27 (Hsp27) as a potential mechanism of action underlying the
      observed therapeutic benefits of DPCs in stroke. This study supports the use of
      stem cells for stroke therapy and implicates a key role of Hsp27 signaling
      pathway in neuroprotection. 

PMID- 24086731
TI  - Tacrolimus does not affect early wound healing in a rodent model of bowel
      anastomoses and abdominal wall closure.
AB  - BACKGROUND: Use of immunosuppressant drugs has been associated with complications
      in wound healing. The calcineurin inhibitor tacrolimus is thought to have a
      relatively low complication rate, but preclinical research has yielded
      contradictory data, prompting the current comprehensive study. METHODS: Three
      groups of 33 male Wistar rats received a daily subcutaneous dose of 0,5, 2 or 5
      mg/kg tacrolimus. A control group received saline. On day 0 a resection of 1 cm
      ileum and 1 cm colon was performed, and end-to-end anastomoses were constructed.
      Ten rats of each group were killed on day 3 and day 5 and the remaining animals
      on day 7. Both anastomoses and the wound in the abdominal wall were analyzed.
      Wound strength was the primary outcome parameter. RESULTS: Mean strength of the
      abdominal wall increased significantly over time in all groups (p<0.0001). Both
      the breaking strength and the bursting pressure of the ileum and colon
      anastomoses followed the same pattern. No differences were observed between
      control and experimental groups. In addition, no consistent differences were
      found between groups regarding wound hydroxyproline content and the activities of
      matrix metalloproteinase-2 and -9. CONCLUSION: Tacrolimus does not affect early
      wound healing.

PMID- 24086732
TI  - "Best practice" skills lab training vs. a "see one, do one" approach in
      undergraduate medical education: an RCT on students' long-term ability to perform
      procedural clinical skills.
AB  - BACKGROUND: Benefits of skills lab training are widely accepted, but there is
      sparse research on its long-term effectiveness. We therefore conducted a
      prospective, randomised controlled-trial to investigate whether in a simulated
      setting students trained according to a "best practice" model (BPSL) perform two
      skills of different complexity (nasogastral tube insertion, NGT; intravenous
      cannulation, IVC) better than students trained with a traditional "see one, do
      one" teaching approach (TRAD), at follow-up of 3 or 6 months. METHODOLOGY AND
      PRINCIPAL FINDINGS: 94 first-year medical students were randomly assigned to one
      of four groups: BPSL training or TRAD teaching with follow-up at 3 (3M) or 6 (6M)
      months. BPSL included structured feedback, practice on manikins, and Peyton's
      "Four-Step-Approach", while TRAD was only based on the "see one - do one"
      principle. At follow-up, manikins were used to assess students' performance by
      two independent blinded video-assessors using binary checklists and a single-item
      global assessment scale. BPSL students scored significantly higher immediately
      after training (NGT: BPSL3M 94.8%+/-0.2 and BPSL6M 95.4%+/-0.3 percentage of
      maximal score +/- SEM; TRAD3M 86.1%+/-0.5 and TRAD6M 84.7%+/-0.4. IVC: BPSL3M
      86.4%+/-0.5 and BPSL6M 88.0%+/-0.5; TRAD3M 73.2%+/-0.7 and TRAD6M 72.5%+/-0.7)
      and lost significantly less of their performance ability at each follow-up (NGT:
      BPSL3M 86.3%+/-0.3 and TRAD3M 70.3%+/-0.6; BPSL6M 89.0%+/-0.3 and TRAD6M 65.4%+/
      0.6; IVC: BPSL3M 79.5%+/-0.5 and TRAD3M 56.5%+/-0.5; BPSL6M 73.2%+/-0.4 and
      TRAD6M 51.5%+/-0.8). In addition, BPSL students were more often rated clinically
      competent at all assessment times. The superiority at assessment after training
      was higher for the more complex skill (IVC), whereas NGT with its lower
      complexity profited more with regard to long-term retention. CONCLUSIONS: This
      study shows that within a simulated setting BPSL is significantly more effective
      than TRAD for skills of different complexity assessed immediately after training
      and at follow-up. The advantages of BPSL training are seen especially in long
      term retention.

PMID- 24086733
TI  - SOCS-1 mediates ubiquitylation and degradation of GM-CSF receptor.
AB  - Granulocyte-macrophage colony-stimulating factor (GM-CSF) and the related
      cytokines interleukin (IL)-3 and IL-5 regulate the production and functional
      activation of hematopoietic cells. GM-CSF acts on monocytes/macrophages and
      granulocytes, and several chronic inflammatory diseases and a number of
      haematological malignancies such as Juvenile myelomonocytic leukaemia (JMML) are
      associated with deregulated GM-CSF receptor (GMR) signaling. The downregulation
      of GMR downstream signaling is mediated in part by the clearance of activated GMR
      via the proteasome, which is dependent on the ubiquitylation of betac signaling
      subunit of GMR via an unknown E3 ubiquitin ligase. Here, we show that suppressor
      of cytokine signaling 1 (SOCS-1), best known for its ability to promote ubiquitin
      mediated degradation of the non-receptor tyrosine kinase Janus kinase 2 (JAK2),
      also targets GMRbetac for ubiquitin-mediated degradation and attenuates GM-CSF
      induced downstream signaling. 

PMID- 24086734
TI  - Autoantibody to interferon-gamma associated with adult-onset immunodeficiency in
      non-HIV individuals in Northern Thailand.
AB  - BACKGROUND: Autoantibody to interferon-gamma (IFN-gamma) has been reported to be
      associated with adult-onset immunodeficiency in patients from Asian countries.
      This study aimed to determine the prevalence of autoantibody to IFN-gamma among
      non-HIV patients in northern Thailand who were repeatedly infected with unusual
      intracellular pathogens. METHODS: A cross-sectional, case-control study was
      conducted between March 2011 and March 2012 at Chiang Mai University Hospital. 20
      cases, non-HIV, aged 18-60 years, presented with at least 2 episodes of culture
      or histopathology proven opportunistic infections were enrolled. Controls
      comprised 20 HIV-infected patients and 20 healthy adults who were age- and sex
      matched with cases. Enzyme-linked immunosorbent assay (ELISA) was used to detect
      the presence of antibody to IFN-gamma. RESULTS: 11 participants in each group
      were female. The mean ages were 48.1+/-6.4, 48.3+/-6.3, and 47.1+/-6.5 years
      among cases, HIV-infected, and healthy controls, respectively. The opportunistic
      infections among 20 cases included disseminated non-tuberculous mycobacterial
      (NTM) infection (19 patients/24 episodes), disseminated penicilliosis marneffei
      (12 patients/12 episodes), and non-typhoidal Salmonella bacteremia (7 patients/8
      episodes). At the cutoff level of 99 percentile of controls, the prevalence of
      autoantibody to IFN-gamma were 100%, 0%, and 0%, among cases, HIV-infected, and
      healthy controls, respectively (p-value <0.001). The mean concentrations of
      antibody to IFN-gamma were 3.279+/-0.662 and 0.939+/-0.630 O.D. among cases with
      and without active opportunistic infection, respectively (p-value<0.001).
      CONCLUSIONS: In northern Thailand, autoantibody to IFN-gamma was strongly
      associated with adult-onset immunodeficiency. The level of antibody to IFN-gamma
      in patients who had active opportunistic infection was relatively higher than
      those without active infection.

PMID- 24086735
TI  - LdFlabarin, a new BAR domain membrane protein of Leishmania flagellum.
AB  - During the Leishmania life cycle, the flagellum undergoes successive assembly and
      disassembly of hundreds of proteins. Understanding these processes necessitates
      the study of individual components. Here, we investigated LdFlabarin, an
      uncharacterized L. donovani flagellar protein. The gene is conserved within the
      Leishmania genus and orthologous genes only exist in the Trypanosoma genus.
      LdFlabarin associates with the flagellar plasma membrane, extending from the base
      to the tip of the flagellum as a helicoidal structure. Site-directed mutagenesis,
      deletions and chimera constructs showed that LdFlabarin flagellar addressing
      necessitates three determinants: an N-terminal potential acylation site and a
      central BAR domain for membrane targeting and the C-terminal domain for flagellar
      specificity. In vitro, the protein spontaneously associates with liposomes,
      triggering tubule formation, which suggests a structural/morphogenetic function.
      LdFlabarin is the first characterized Leishmania BAR domain protein, and the
      first flagellum-specific BAR domain protein. 

PMID- 24086736
TI  - Analyses of potential predictive markers and survival data for a response to
      sunitinib in patients with metastatic renal cell carcinoma.
AB  - BACKGROUND: Patients with metastatic clear cell renal cell carcinoma (ccRCC) are
      frequently treated with tyrosine kinase inhibitors (TKI) such as sunitinib. It
      inhibits angiogenic pathways by mainly targeting the receptors of VEGF and PDGF.
      In ccRCC, angiogenesis is characterized by the inactivation of the von Hippel
      Lindau gene (VHL) which in turn leads to the induction of HIF1alpha target genes
      such as CA9 and VEGF. Furthermore, the angiogenic phenotype of ccRCC is also
      reflected by endothelial markers (CD31, CD34) or other tumor-promoting factors
      like Ki67 or survivin. METHODS: Tissue microarrays from primary tumor specimens
      of 42 patients with metastatic ccRCC under sunitinib therapy were
      immunohistochemically stained for selected markers related to angiogenesis. The
      prognostic and predictive potential of theses markers was assessed on the basis
      of the objective response rate which was evaluated according to the RECIST
      criteria after 3, 6, 9 months and after last report (12-54 months) of sunitinib
      treatment. Additionally, VHL copy number and mutation analyses were performed on
      DNA from cryo-preserved tumor tissues of 20 ccRCC patients. RESULTS:
      Immunostaining of HIF-1alpha, CA9, Ki67, CD31, pVEGFR1, VEGFR1 and -2,
      pPDGFRalpha and -beta was significantly associated with the sunitinib response
      after 6 and 9 months as well as last report under therapy. Furthermore, HIF
      1alpha, CA9, CD34, VEGFR1 and -3 and PDGRFalpha showed significant associations
      with progression-free survival (PFS) and overall survival (OS). In multivariate
      Cox proportional hazards regression analyses high CA9 membrane staining and a
      response after 9 months were independent prognostic factors for longer OS.
      Frequently observed copy number loss and mutation of VHL gene lead to altered
      expression of VHL, HIF-1alpha, CA9, and VEGF. CONCLUSIONS: Immunoexpression of
      HIF-1alpha, CA9, Ki67, CD31, pVEGFR1, VEGFR1 and -2, pPDGFRalpha and -beta in the
      primary tumors of metastatic ccRCC patients might support the prediction of a
      good response to sunitinib treatment.

PMID- 24086737
TI  - Endoplasmic reticulum stress is involved in the response of human laryngeal
      carcinoma cells to Carboplatin but is absent in Carboplatin-resistant cells.
AB  - The major obstacle of successful tumor treatment with carboplatin (CBP) is the
      development of drug resistance. In the present study, we found that following
      treatment with CBP the amount of platinum which enters the human laryngeal
      carcinoma (HEp2)-derived CBP-resistant (7T) cells is reduced relative to the
      parental HEp2. As a consequence, the formation of reactive oxidative species
      (ROS) is reduced, the induction of endoplasmic reticulum (ER) stress is
      diminished, the amount of inter- and intrastrand cross-links is lower, and the
      induction of apoptosis is depressed. In HEp2 cells, ROS scavenger tempol,
      inhibitor of ER stress salubrinal, as well as gene silencing of ER stress marker
      CCAAT/enhancer-binding protein (CHOP) increases their survival and renders them
      as resistant to CBP as 7T cell subline but did not influence the survival of 7T
      cells. Our results suggest that in HEp2 cells CBP-induced ROS is a stimulus for
      ER stress. To the contrary, despite the ability of CBP to induce formation of ROS
      and activate ER stress in 7T cells, the cell death mechanism in 7T cells is
      independent of ROS induction and activation of ER stress. The novel signaling
      pathway of CBP-driven toxicity that was found in the HEp2 cell line, i.e.
      increased ROS formation and induction of ER stress, may be predictive for
      therapeutic response of epithelial cancer cells to CBP-based therapy. 

PMID- 24086738
TI  - Effects of short-term nutritional interventions on right ventricular function in
      healthy men.
AB  - BACKGROUND: A physiological model of increased plasma nonesterified fatty acid
      (NEFA) levels result in myocardial triglyceride (TG) accumulation, which is
      related to cardiac dysfunction. A pathophysiological model of increased plasma
      NEFA levels result in hepatic steatosis, which has been linked to abnormal
      myocardial energy metabolism. Hepatic steatosis is accompanied by hepatic
      inflammation, reflected by plasma cholesteryl ester transfer protein (CETP)
      levels. The current study aimed to investigate effects of these models via
      different nutritional interventions on right ventricular (RV) function. METHODS:
      Fifteen men (age 25.0+/-6.6 years) were included and underwent magnetic resonance
      imaging and spectroscopy in this prospective crossover intervention study. RV
      function, myocardial and hepatic TG content, and CETP levels were assessed on
      three occasions: after normal diet, very low-calorie diet (VLCD, physiological
      model) and high-fat high-energy (HFHE, pathophysiological model) diet (all 3-days
      diets, randomly ordered, washout phase at least 14 days). RESULTS: VLCD induced a
      decrease in mean E deceleration by 27%. Myocardial TG content increased by 55%,
      whereas hepatic TG content decreased by 32%. Plasma CETP levels decreased by 14%
      (all P<0.05). HFHE diet induced a decrease in E/A by 19% (P<0.05). Myocardial TG
      content did not change, whereas hepatic TG content increased by 112% (P<0.01).
      Plasma CETP levels increased by 14% (P<0.05). CONCLUSIONS: These findings show
      that RV diastolic function is impaired after short-term VLCD and HFHE diet in
      healthy men, respectively a physiological and a pathophysiological model of
      increased plasma NEFA levels. After short-term VLCD, myocardial lipotoxicity may
      be of importance in decreased RV diastolic function. RV diastolic dysfunction is
      accompanied by increased hepatic TG content and plasma CETP levels after short
      term HFHE diet, suggesting that systemic inflammation reflecting local macrophage
      infiltration in the heart may be involved in RV dysfunction.

PMID- 24086739
TI  - A novel MAPT mutation, G55R, in a frontotemporal dementia patient leads to
      altered Tau function.
AB  - Over two dozen mutations in the gene encoding the microtubule associated protein
      tau cause a variety of neurodegenerative dementias known as tauopathies,
      including frontotemporal dementia (FTD), PSP, CBD and Pick's disease. The vast
      majority of these mutations map to the C-terminal region of tau possessing
      microtubule assembly and microtubule dynamics regulatory activities as well as
      the ability to promote pathological tau aggregation. Here, we describe a novel
      and non-conservative tau mutation (G55R) mapping to an alternatively spliced exon
      encoding part of the N-terminal region of the protein in a patient with the
      behavioral variant of FTD. Although less well understood than the C-terminal
      region of tau, the N-terminal region can influence both MT mediated effects as
      well as tau aggregation. The mutation changes an uncharged glycine to a basic
      arginine in the midst of a highly conserved and very acidic region. In vitro, 4
      repeat G55R tau nucleates microtubule assembly more effectively than wild-type 4
      repeat tau; surprisingly, this effect is tau isoform specific and is not observed
      in a 3-repeat G55R tau versus 3-repeat wild-type tau comparison. In contrast, the
      G55R mutation has no effect upon the abilities of tau to regulate MT growing and
      shortening dynamics or to aggregate. Additionally, the mutation has no effect
      upon kinesin translocation in a microtubule gliding assay. Together, (i) we have
      identified a novel tau mutation mapping to a mutation deficient region of the
      protein in a bvFTD patient, and (ii) the G55R mutation affects the ability of tau
      to nucleate microtubule assembly in vitro in a 4-repeat tau isoform specific
      manner. This altered capability could markedly affect in vivo microtubule
      function and neuronal cell biology. We consider G55R to be a candidate mutation
      for bvFTD since additional criteria required to establish causality are not yet
      available for assessment. 

PMID- 24086740
TI  - Recently deglaciated high-altitude soils of the Himalaya: diverse environments,
      heterogenous bacterial communities and long-range dust inputs from the upper
      troposphere.
AB  - BACKGROUND: The Himalaya with its altitude and geographical position forms a
      barrier to atmospheric transport, which produces much aqueous-particle monsoon
      precipitation and makes it the largest continuous ice-covered area outside polar
      regions. There is a paucity of data on high-altitude microbial communities, their
      native environments and responses to environmental-spatial variables relative to
      seasonal and deglaciation events. METHODOLOGY/PRINCIPAL FINDINGS: Soils were
      sampled along altitude transects from 5000 m to 6000 m to determine
      environmental, spatial and seasonal factors structuring bacterial communities
      characterized by 16 S rRNA gene deep sequencing. Dust traps and fresh-snow
      samples were used to assess dust abundance and viability, community structure and
      abundance of dust associated microbial communities. Significantly different
      habitats among the altitude-transect samples corresponded to both
      phylogenetically distant and closely-related communities at distances as short as
      50 m showing high community spatial divergence. High within-group variability
      that was related to an order of magnitude higher dust deposition obscured
      seasonal and temporal rearrangements in microbial communities. Although dust
      particle and associated cell deposition rates were highly correlated, seasonal
      dust communities of bacteria were distinct and differed significantly from
      recipient soil communities. Analysis of closest relatives to dust OTUs, HYSPLIT
      back-calculation of airmass trajectories and small dust particle size (4-12 um)
      suggested that the deposited dust and microbes came from distant continental,
      lacustrine and marine sources, e.g. Sahara, India, Caspian Sea and Tibetan
      plateau. Cyanobacteria represented less than 0.5% of microbial communities
      suggesting that the microbial communities benefitted from (co)deposited carbon
      which was reflected in the psychrotolerant nature of dust-particle associated
      bacteria. CONCLUSIONS/SIGNIFICANCE: The spatial, environmental and temporal
      complexity of the high-altitude soils of the Himalaya generates ongoing
      disturbance and colonization events that subject heterogeneous microniches to
      stochastic colonization by far away dust associated microbes and result in the
      observed spatially divergent bacterial communities.

PMID- 24086741
TI  - The arbuscular mycorrhizal fungal community response to warming and grazing
      differs between soil and roots on the Qinghai-Tibetan plateau.
AB  - Arbuscular mycorrhizal (AM) fungi form symbiotic associations with most plant
      species in terrestrial ecosystems, and are affected by environmental variations.
      To reveal the impact of disturbance on an AM fungal community under future global
      warming, we examined the abundance and community composition of AM fungi in both
      soil and mixed roots in an alpine meadow on the Qinghai-Tibetan Plateau, China.
      Warming and grazing had no significant effect on AM root colonization, spore
      density and extraradical hyphal density. A total of 65 operational taxonomic
      units (OTUs) of AM fungi were identified from soil and roots using molecular
      techniques. AM fungal OTU richness was higher in soil (54 OTUs) than in roots (34
      OTUs), and some AM fungi that differed between soil and roots, showed
      significantly biased occurrence to warming or grazing. Warming and grazing did
      not significantly affect AM fungal OTU richness in soil, but warming with grazing
      significantly increased AM fungal OTU richness in roots compared to the grazing
      only treatment. Non-metric multidimensional scaling analysis showed that the AM
      fungal community composition was significantly different between soil and roots,
      and was significantly affected by grazing in roots, whereas in soil it was
      significantly affected by warming and plant species richness. The results suggest
      that the AM fungal community responds differently to warming and grazing in soil
      compared with roots. This study provides insights into the role of AM fungi under
      global environmental change scenarios in alpine meadows of the Qinghai-Tibetan
      Plateau. 

PMID- 24086742
TI  - Field-portable pixel super-resolution colour microscope.
AB  - Based on partially-coherent digital in-line holography, we report a field
      portable microscope that can render lensfree colour images over a wide field-of
      view of e.g., >20 mm(2). This computational holographic microscope weighs less
      than 145 grams with dimensions smaller than 17*6*5 cm, making it especially
      suitable for field settings and point-of-care use. In this lensfree imaging
      design, we merged a colorization algorithm with a source shifting based multi
      height pixel super-resolution technique to mitigate 'rainbow' like colour
      artefacts that are typical in holographic imaging. This image processing scheme
      is based on transforming the colour components of an RGB image into YUV colour
      space, which separates colour information from brightness component of an image.
      The resolution of our super-resolution colour microscope was characterized using
      a USAF test chart to confirm sub-micron spatial resolution, even for
      reconstructions that employ multi-height phase recovery to handle dense and
      connected objects. To further demonstrate the performance of this colour
      microscope Papanicolaou (Pap) smears were also successfully imaged. This field
      portable and wide-field computational colour microscope could be useful for tele
      medicine applications in resource poor settings. 

PMID- 24086743
TI  - High-level expression, purification and characterization of a constitutively
      active thromboxane A2 receptor polymorphic variant.
AB  - G protein-coupled receptors (GPCRs) exhibit some level of basal signaling even in
      the absence of a bound agonist. This basal or constitutive signaling can have
      important pathophysiological roles. In the past few years, a number of high
      resolution crystal structures of GPCRs have been reported, including two crystal
      structures of constitutively active mutants (CAM) of the dim-light receptor,
      rhodopsin. The structural characterizations of CAMs are impeded by the lack of
      proper expression systems. The thromboxane A2 receptor (TP) is a GPCR that
      mediates vasoconstriction and promotes thrombosis in response to the binding of
      thromboxane. Here, we report on the expression and purification of a genetic
      variant and CAM in TP, namely A160T, using tetracycline-inducible HEK293S-TetR
      and HEK293S (GnTI-)-TetR cell lines. Expression of the TP and the A160T genes in
      these mammalian cell lines resulted in a 4-fold increase in expression to a level
      of 15.8 +/-0.3 pmol of receptor/mg of membrane protein. The receptors expressed
      in the HEK293S (GnTI(-))-TetR cell line showed homogeneous glycosylation. The
      functional yield of the receptors using a single step affinity purification was
      45 ug/106 cells. Temperature- dependent secondary structure changes of the
      purified TP and A160T receptors were characterized using circular dichroism (CD)
      spectropolarimetry. The CD spectra shows that the loss of activity or thermal
      sensitivity that was previously observed for the A160T mutant, is not owing to
      large unfolding of the protein but rather to a more subtle effect. This is the
      first study to report on the successful high-level expression, purification, and
      biophysical characterization of a naturally occurring, diffusible ligand
      activated GPCR CAM.

PMID- 24086744
TI  - Steps towards preventive HIV treatment in Fujian, China: problems identified via
      an assessment of initial antiretroviral therapy provision.
AB  - BACKGROUND: At the end of 2009, a total of 501 AIDS patients were receiving
      antiretroviral therapy (ART) in Fujian Province in China, yet there were no
      assessments to determine treatment efficacy and HIV-1 preventive potency under
      the current health care delivery system. METHODS: During the period of 2005-2009,
      we assessed the outcomes of initial ART by following up 381 patients for 12
      months in Fujian Province. CD4+ T-lymphocyte (CD4) count, plasma viral load (VL),
      and patient characteristics were analysed. The results were compared between 4
      groups divided by the baseline CD4 values at the 25, 50 (median), and 75
      percentiles. FINDINGS: Over three-quarters of the subjects reported heterosexual
      contact as the probable route of transmission. After 12 months of ART, CD4
      recovery varied between the 4 groups (P < 0.001), but VL sharply declined
      regardless of the baseline CD4 count (P = 0.136). Although this VL decline
      indicates the potency of ART as an HIV-1 prevention tool, the time between
      positive diagnosis and ART initiation suggests serious delay in both diagnosis
      and treatment; the medians of periods for the lowest and highest baseline CD4
      quartiles were 1.2 and 9.6 months, respectively. CONCLUSION: Current limitations
      in VL determination make it difficult to assess the efficacy of initial ART, and
      delays in diagnosis and treatment suggest that subjects contributed to HIV-1
      transmission while they were not receiving ART. The current National Free ART
      scheme does not provide free treatment for sexually transmitted infection (STI),
      and there is no link between ART and the STI care delivery system. This may
      interfere with the HIV-1 preventive potency of ART. We highly recommend
      establishing a collaborating mechanism with STI care, strengthening the VL
      determination system, and promoting HIV tests and early ART initiation.

PMID- 24086745
TI  - Modifications of hippocampal circuits and early disruption of adult neurogenesis
      in the tg2576 mouse model of Alzheimer's disease.
AB  - At advanced stages of Alzheimer's disease, cognitive dysfunction is accompanied
      by severe alterations of hippocampal circuits that may largely underlie memory
      impairments. However, it is likely that anatomical remodeling in the hippocampus
      may start long before any cognitive alteration is detected. Using the well
      described Tg2576 mouse model of Alzheimer's disease that develops progressive age
      dependent amyloidosis and cognitive deficits, we examined whether specific stages
      of the disease were associated with the expression of anatomical markers of
      hippocampal dysfunction. We found that these mice develop a complex pattern of
      changes in their dentate gyrus with aging. Those include aberrant expression of
      neuropeptide Y and reduced levels of calbindin, reflecting a profound remodeling
      of inhibitory and excitatory circuits in the dentate gyrus. Preceding these
      changes, we identified severe alterations of adult hippocampal neurogenesis in
      Tg2576 mice. We gathered converging data in Tg2576 mice at young age, indicating
      impaired maturation of new neurons that may compromise their functional
      integration into hippocampal circuits. Thus, disruption of adult hippocampal
      neurogenesis occurred before network remodeling in this mouse model and therefore
      may account as an early event in the etiology of Alzheimer's pathology.
      Ultimately, both events may constitute key components of hippocampal dysfunction
      and associated cognitive deficits occurring in Alzheimer's disease. 

PMID- 24086746
TI  - The Iroquois complex is required in the dorsal mesoderm to ensure normal heart
      development in Drosophila.
AB  - Drosophila heart development is an invaluable system to study the orchestrated
      action of numerous factors that govern cardiogenesis. Cardiac progenitors arise
      within specific dorsal mesodermal regions that are under the influence of
      temporally coordinated actions of multiple signaling pathways. The Drosophila
      Iroquois complex (Iro-C) consists of the three homeobox transcription factors
      araucan (ara), caupolican (caup) and mirror (mirr). The Iro-C has been shown to
      be involved in tissue patterning leading to the differentiation of specific
      structures, such as the lateral notum and dorsal head structures and in
      establishing the dorsal-ventral border of the eye. A function for Iro-C in
      cardiogenesis has not been investigated yet. Our data demonstrate that loss of
      the whole Iro complex, as well as loss of either ara/caup or mirr only, affect
      heart development in Drosophila. Furthermore, the data indicate that the GATA
      factor Pannier requires the presence of Iro-C to function in cardiogenesis.
      Furthermore, a detailed expression pattern analysis of the members of the Iro-C
      revealed the presence of a possibly novel subpopulation of Even-skipped
      expressing pericardial cells and seven pairs of heart-associated cells that have
      not been described before. Taken together, this work introduces Iro-C as a new
      set of transcription factors that are required for normal development of the
      heart. As the members of the Iro-C may function, at least partly, as competence
      factors in the dorsal mesoderm, our results are fundamental for future studies
      aiming to decipher the regulatory interactions between factors that determine
      different cell fates in the dorsal mesoderm. 

PMID- 24086747
TI  - Effects of hand orientation on motor imagery--event related potentials suggest
      kinesthetic motor imagery to solve the hand laterality judgment task.
AB  - Motor imagery (MI) refers to the process of imagining the execution of a specific
      motor action without actually producing an overt movement. Two forms of MI have
      been distinguished: visual MI and kinesthetic MI. To distinguish between these
      forms of MI we employed an event related potential (ERP) study to measure
      interference effects induced by hand orientation manipulations in a hand
      laterality judgement task. We hypothesized that this manipulation should only
      affect kinesthetic MI but not visual MI. The ERPs elicited by rotated hand
      stimuli contained the classic rotation related negativity (RRN) with respect to
      palm view stimuli. We observed that laterally rotated stimuli led to a more
      marked RRN than medially rotated stimuli. This RRN effect was observed when
      participants had their hands positioned in either a straight (control) or an
      inward rotated posture, but not when their hands were positioned in an outward
      rotated posture. Posture effects on the ERP-RRN have not previously been studied.
      Apparently, a congruent hand posture (hands positioned in an outward rotated
      fashion) facilitates the judgement of the otherwise more demanding laterally
      rotated hand stimuli. These ERP findings support a kinesthetic interpretation of
      MI involved in solving the hand laterality judgement task. The RRN may be used as
      a non-invasive marker for kinesthetic MI and seems useful in revealing the covert
      behavior of MI in e.g. rehabilitation programs. 

PMID- 24086748
TI  - A novel cationic microbubble coated with stearic acid-modified polyethylenimine
      to enhance DNA loading and gene delivery by ultrasound.
AB  - A novel cationic microbubble (MB) for improvement of the DNA loading capacity and
      the ultrasound-mediated gene delivery efficiency has been developed; it has been
      prepared with commercial lipids and a stearic acid modified polyethylenimine 600
      (Stearic-PEI600) polymer synthesized via acylation reaction of branched PEI600
      and stearic acid mediated by N, N'-carbonyldiimidazole (CDI). The MBs'
      concentration, size distribution, stability and zeta potential (zeta-potential)
      were measured and the DNA loading capacity was examined as a function of the
      amount of Stearic-PEI600. The gene transfection efficiency and cytotoxicity were
      also examined using breast cancer MCF-7 cells via the reporter plasmid pCMV-Luc,
      encoding the firefly luciferase gene. The results showed that the Stearic-PEI600
      polymer caused a significant increase in magnitude of zeta-potential of MBs. The
      addition of DNA into cationic MBs can shift zeta-potentials from positive to
      negative values. The DNA loading capacity of the MBs grew linearly from (5+/-0.2)
      *10-3 pg/um2 to (20+/-1.8) *10-3 pg/um2 when Stearic-PEI600 was increased from 5
      mol% to 30 mol%. Transfection of MCF-7 cells using 5% PEI600 MBs plus ultrasound
      exposure yielded 5.76+/-2.58*103 p/s/cm2/sr average radiance intensity, was 8.97-
      and 7.53-fold higher than those treated with plain MBs plus ultrasound (6.41+/
      5.82) *102 p/s/cm2/sr, (P<0.01) and PEI600 MBs without ultrasound (7.65+/-6.18)
      *102 p/s/cm2/sr, (P<0.01), respectively. However, the PEI600 MBs showed slightly
      higher cytotoxicity than plain MBs. The cells treated with PEI600-MBs and plain
      MBs plus ultrasound showed 59.5+/-6.1% and 71.4+/-7.1% cell viability,
      respectively. In conclusion, our study demonstrated that the novel cationic MBs
      were able to increase DNA loading capacity and gene transfection efficiency and
      could be potentially applied in targeted gene delivery and therapy.

PMID- 24086749
TI  - Brown Recluse spider bite mediated hemolysis: clinical features, a possible role
      for complement inhibitor therapy, and reduced RBC surface glycophorin A as a
      potential biomarker of venom exposure.
AB  - BACKGROUND: The venom of Loxosceles reclusa (Brown Recluse spider) can cause a
      severe, life-threatening hemolysis in humans for which no therapy is currently
      available in the USA beyond supportive measures. Because this hemolysis is
      uncommon, relatively little is known about its clinical manifestation, diagnosis,
      or management. Here, we aimed to clarify the clinical details of envenomation, to
      determine the efficacy of the complement inhibitor eculizumab to prevent the
      hemolysis in vitro, and to investigate markers of exposure to Brown Recluse
      venom. STUDY DESIGN AND METHODS: We performed a 10-year chart review of cases of
      Brown Recluse spider bite-mediated hemolysis at our institution. We also designed
      an in vitro assay to test the efficacy of eculizumab to inhibit hemolysis of
      venom exposed red blood cells. Finally, we compared levels of CD55, CD59 and
      glycophorin A on venom exposed versus venom-naive cells. RESULTS: Most victims of
      severe Brown Recluse spider mediated hemolysis at our institution are children
      and follow an unpredictable clinical course. Brown Recluse spider bite mediated
      hemolysis is reduced by 79.2% (SD=18.8%) by eculizumab in vitro. Erythrocyte
      glycophorin A, but not CD55 or CD59, is reduced after red blood cells are
      incubated with venom in vitro. CONCLUSION: Taken together, our laboratory data
      and clinical observations indicate that L. reclusa venom exposure results in non
      specific antibody and complement fixation on red blood cells, resulting in
      complement mediated hemolysis that is curtailed by the complement inhibitor
      eculizumab in vitro. Glycophorin A measurement by flow cytometry may help to
      identify victims of L. reclusa envenomation.

PMID- 24086750
TI  - Small RNA profiling of influenza A virus-infected cells identifies miR-449b as a
      regulator of histone deacetylase 1 and interferon beta.
AB  - The mammalian antiviral response relies on the alteration of cellular gene
      expression, to induce the production of antiviral effectors and regulate their
      activities. Recent research has indicated that virus infections can induce the
      accumulation of cellular microRNA (miRNA) species that influence the stability of
      host mRNAs and their protein products. To determine the potential for miRNA
      regulation of cellular responses to influenza A virus infection, small RNA
      profiling was carried out using next generation sequencing. Comparison of miRNA
      expression profiles in uninfected human A549 cells to cells infected with
      influenza A virus strains A/Udorn/72 and A/WSN/33, revealed virus-induced changes
      in miRNA abundance. Gene expression analysis identified mRNA targets for a cohort
      of highly inducible miRNAs linked to diverse cellular functions. Experiments
      demonstrate that the histone deacetylase, HDAC1, can be regulated by influenza
      inducible miR-449b, resulting in altered mRNA and protein levels. Expression of
      miR-449b enhances virus and poly(I:C) activation of the IFNbeta promoter, a
      process known to be negatively regulated by HDAC1. These findings demonstrate
      miRNA induction by influenza A virus infection and elucidate an example of miRNA
      control of antiviral gene expression in human cells, defining a role for miR-449b
      in regulation of HDAC1 and antiviral cytokine signaling. 

PMID- 24086751
TI  - The effect of alcohols on red blood cell mechanical properties and membrane
      fluidity depends on their molecular size.
AB  - The role of membrane fluidity in determining red blood cell (RBC) deformability
      has been suggested by a number of studies. The present investigation evaluated
      alterations of RBC membrane fluidity, deformability and stability in the presence
      of four linear alcohols (methanol, ethanol, propanol and butanol) using
      ektacytometry and electron paramagnetic resonance (EPR) spectroscopy. All
      alcohols had a biphasic effect on deformability such that it increased then
      decreased with increasing concentration; the critical concentration for reversal
      was an inverse function of molecular size. EPR results showed biphasic changes of
      near-surface fluidity (i.e., increase then decrease) and a decreased fluidity of
      the lipid core; rank order of effectiveness was butanol > propanol > ethanol >
      methanol, with a significant correlation between near-surface fluidity and
      deformability (r = 0.697; p<0.01). The presence of alcohol enhanced the
      impairment of RBC deformability caused by subjecting cells to 100 Pa shear stress
      for 300 s, with significant differences from control being observed at higher
      concentrations of all four alcohols. The level of hemolysis was dependent on
      molecular size and concentration, whereas echinocytic shape transformation (i.e.,
      biconcave disc to crenated morphology) was observed only for ethanol and
      propanol. These results are in accordance with available data obtained on model
      membranes. They document the presence of mechanical links between RBC
      deformability and near-surface membrane fluidity, chain length-dependence of the
      ability of alcohols to alter RBC mechanical behavior, and the biphasic response
      of RBC deformability and near-surface membrane fluidity to increasing alcohol
      concentrations. 

PMID- 24086752
TI  - STAT1 regulates human glutaminase 1 promoter activity through multiple binding
      sites in HIV-1 infected macrophages.
AB  - Mononuclear phagocytes (MP, macrophages and microglia), the main targets of HIV-1
      infection in the brain, play a pathogenic role in HIV-associated neurocognitive
      disorders (HAND) through the production and release of various soluble neurotoxic
      factors including glutamate. We have previously reported that glutaminase (GLS),
      the glutamate-generating enzyme, is upregulated in HIV-1 infected MP and in the
      brain tissues of HIV dementia individuals, and that HIV-1 or interferon-alpha
      (IFN-alpha) regulates human glutaminase 1 (GLS1) promoter through signal
      transducer and activator of transcription 1 (STAT1) phosphorylation in
      macrophages. However, there are multiple putative STAT1 binding sites in human
      GLS1 promoter, the exact molecular mechanism of how HIV-1 or IFN-alpha regulates
      human GLS1 promoter remains unclear. To further study the function of the
      putative STAT1 binding sites, we mutated the sequence of each binding site to
      ACTAGTCTC and found that six mutants (mut 1,3,4,5,7,8) had significantly higher
      promoter activity and two mutants (mut 2 and mut 6) completely lost the promoter
      activity compared with the wild type. To determine whether sites 2 and 6 could
      interfere with other inhibitory sites, particularly the nearby inhibitory sites 3
      and 5, we made double mutants dmut 2/3 and dmut 5/6, and found that both the
      double mutants had significantly higher activity than the wild type, indicating
      that sites 3 and 5 are critical inhibitory elements, while sites 2 and 6 are
      excitatory elements. ChIP assay verified that STAT1 could bind with sites 2/3 and
      5/6 within human GLS1 promoter in IFN-alpha stimulated or HIV-1-infected monocyte
      derived macrophages. Interestingly, we found that rat Gls1 promoter was regulated
      through a similar way as human GLS1 promoter. Together, our data identified
      critical elements that regulate GLS1 promoter activity. 

PMID- 24086753
TI  - Vibrio cholerae porin OmpU induces pro-inflammatory responses, but down-regulates
      LPS-mediated effects in RAW 264.7, THP-1 and human PBMCs.
AB  - Vibrio cholerae porin OmpU plays a crucial role in the survival of the organism
      in the human gut. Various observations suggest critical involvement of OmpU in V.
      cholerae pathogenesis. However, OmpU is poorly characterized in terms of its
      ability to evoke cellular responses, particularly in the context of host immune
      system. Therefore, towards characterizing V. cholerae OmpU for its host
      immunomodulatory functions, we have studied the ability of OmpU to elicit pro
      inflammatory responses in a range of immune cells which include, mouse RAW 264.7
      macrophages, human THP-1 monocytes and human PBMCs. We have observed that
      purified OmpU induces pro-inflammatory responses in terms of production of NO,
      TNFalpha and IL-6. Interestingly, pre-treatment of the cells with OmpU suppresses
      the production of NO, TNFalpha, IL-6 as well as IL-12 upon subsequent activation
      with LPS. Our results therefore suggest that V. cholerae OmpU may have a
      differential regulatory role in terms of host immunomodulatory function: it can
      induce pro-inflammatory responses in target host immune cells, whereas it can
      also exert suppressive effect on LPS-induced pro-inflammatory responses. In
      addition, our study indicates that purified OmpU may have the ability to skew the
      Th1 response towards the Th2 response, presumably via suppression of IL-12
      production. 

PMID- 24086754
TI  - Ubiquilin 2 is not associated with tau pathology.
AB  - Accumulation of aberrant proteins in inclusion bodies is a hallmark of many
      neurodegenerative diseases. Impairment of proteolytic systems is a common event
      in these protein misfolding diseases. Recently, mutations in the UBQLN 2 gene
      encoding ubiquilin 2 have been identified in X-linked amyotrophic lateral
      sclerosis (ALS). Furthermore, ubiquilin 2 is associated with inclusions in
      familial and sporadic ALS/dementia, synucleinopathies and polyglutamine diseases.
      Ubiquilin 2 exerts a regulatory role in proteostasis and thus it has been
      suggested that ubiquilin 2 pathology may be a common event in neurodegenerative
      diseases. Tauopathies, a heterogenous group of neurodegenerative diseases
      accompanied with dementia, are characterized by inclusions of the microtubule
      binding protein tau. In the present study, we investigate whether ubiquilin 2 is
      connected with tau pathology in Alzheimer's disease (AD), supranuclear palsy
      (PSP) and Pick's disease (PiD) and familial cases with frontotemporal dementia
      and parkinsonism linked to chromosome 17 (FTDP-17). We show that ubiquilin 2
      positive inclusions are absent in these tauopathies. Furthermore, we find
      decreased ubiquilin 2 protein levels in AD patients, but our results do not
      indicate a correlation with tau pathology. Our data show no evidence for
      involvement of ubiquilin 2 and indicate that other mechanisms underly the
      proteostatic disturbances in tauopathies. 

PMID- 24086755
TI  - Ecological energetics of an abundant aerial insectivore, the Purple Martin.
AB  - The atmospheric boundary layer and lower free atmosphere, or aerosphere, is
      increasingly important for human transportation, communication, environmental
      monitoring, and energy production. The impacts of anthropogenic encroachment into
      aerial habitats are not well understood. Insectivorous birds and bats are
      inherently valuable components of biodiversity and play an integral role in
      aerial trophic dynamics. Many of these insectivores are experiencing range-wide
      population declines. As a first step toward gaging the potential impacts of these
      declines on the aerosphere's trophic system, estimates of the biomass and energy
      consumed by aerial insectivores are needed. We developed a suite of energetics
      models for one of the largest and most common avian aerial insectivores in North
      America, the Purple Martin (Prognesubis). The base model estimated that Purple
      Martins consumed 412 (+/- 104) billion insects*y-1 with a biomass of 115,860 (+/-
      29,192) metric tonnes*y-1. During the breeding season Purple Martins consume 10.3
      (+ 3.0) kg of prey biomass per km3 of aerial habitat, equal to about 36,000
      individual insects*km-3. Based on these calculations, the cumulative seasonal
      consumption of insects*km-3 is greater in North America during the breeding
      season than during other phases of the annual cycle, however the maximum daily
      insect consumption*km-3 occurs during fall migration. This analysis provides the
      first range-wide quantitative estimate of the magnitude of the trophic impact of
      this large and common aerial insectivore. Future studies could use a similar
      modeling approach to estimate impacts of the entire guild of aerial insectivores
      at a variety of temporal and spatial scales. These analyses would inform our
      understanding of the impact of population declines among aerial insectivores on
      the aerosphere's trophic dynamics.

PMID- 24086756
TI  - Novel CIC point mutations and an exon-spanning, homozygous deletion identified in
      oligodendroglial tumors by a comprehensive genomic approach including
      transcriptome sequencing.
AB  - Oligodendroglial tumors form a distinct subgroup of gliomas, characterized by a
      better response to treatment and prolonged overall survival. Most
      oligodendrogliomas and also some oligoastrocytomas are characterized by a unique
      and typical unbalanced translocation, der(1,19), resulting in a 1p/19q co
      deletion. Candidate tumor suppressor genes targeted by these losses, CIC on
      19q13.2 and FUBP1 on 1p31.1, were only recently discovered. We analyzed 17
      oligodendrogliomas and oligoastrocytomas by applying a comprehensive approach
      consisting of RNA expression analysis, DNA sequencing of CIC, FUBP1, IDH1/2, and
      array CGH. We confirmed three different genetic subtypes in our samples: i) the
      "oligodendroglial" subtype with 1p/19q co-deletion in twelve out of 17 tumors;
      ii) the "astrocytic" subtype in three tumors; iii) the "other" subtype in two
      tumors. All twelve tumors with the 1p/19q co-deletion carried the most common
      IDH1 R132H mutation. In seven of these tumors, we found protein-disrupting point
      mutations in the remaining allele of CIC, four of which are novel. One of these
      tumors also had a deleterious mutation in FUBP1. Only by integrating RNA
      expression and array CGH data, were we able to discover an exon-spanning
      homozygous microdeletion within the remaining allele of CIC in an additional
      tumor with 1p/19q co-deletion. Therefore we propose that the mutation rate might
      be underestimated when looking at sequence variants alone. In conclusion, the
      high frequency and the spectrum of CIC mutations in our 1p/19q-codeleted tumor
      cohort support the hypothesis that CIC acts as a tumor suppressor in these
      tumors, whereas FUBP1 might play only a minor role. 

PMID- 24086757
TI  - The T-cell oncogene Tal2 Is a Target of PU.1 and upregulated during
      osteoclastogenesis.
AB  - Transcription factors play a crucial role in regulating differentiation processes
      during human life and are important in disease. The basic helix-loop-helix
      transcription factors Tal1 and Lyl1 play a major role in the regulation of gene
      expression in the hematopoietic system and are involved in human leukemia. Tal2,
      which belongs to the same family of transcription factors as Tal1 and Lyl1, is
      also involved in human leukaemia. However, little is known regarding the
      expression and regulation of Tal2 in hematopoietic cells. Here we show that Tal2
      is expressed in hematopoietic cells of the myeloid lineage. Interestingly, we
      found that usage of the Tal2 promoter is different in human and mouse cells. Two
      promoters, hP1 and hP2 drive Tal2 expression in human erythroleukemia K562 cells,
      however in mouse RAW cells only the mP1 promoter is used. Furthermore, we found
      that Tal2 expression is upregulated during oesteoclastogenesis. We show that Tal2
      is a direct target gene of the myeloid transcription factor PU.1, which is a key
      transcription factor for osteoclast gene expression. Strikingly, PU.1 binding to
      the P1 promoter is conserved between mouse and human, but PU.1 binding to P2 was
      only detected in human K562 cells. Additionally, we provide evidence that Tal2
      influences the expression of the osteoclastic differentiation gene TRACP. These
      findings provide novel insight into the expression control of Tal2 in
      hematopoietic cells and reveal a function of Tal2 as a regulator of gene
      expression during osteoclast differentiation. 

PMID- 24086758
TI  - Alcohol affects neuronal substrates of response inhibition but not of perceptual
      processing of stimuli signalling a stop response.
AB  - Alcohol impairs inhibitory control, including the ability to terminate an
      initiated action. While there is increasing knowledge about neural mechanisms
      involved in response inhibition, the level at which alcohol impairs such
      mechanisms remains poorly understood. Thirty-nine healthy social drinkers
      received either 0.4 g/kg or 0.8 g/kg of alcohol, or placebo, and performed two
      variants of a Visual Stop-signal task during acquisition of functional magnetic
      resonance imaging (fMRI) data. The two task variants differed only in their
      instructions: in the classic variant (VSST), participants inhibited their
      response to a "Go-stimulus" when it was followed by a "Stop-stimulus". In the
      control variant (VSST_C), participants responded to the "Go-stimulus" even if it
      was followed by a "Stop-stimulus". Comparison of successful Stop-trials
      (Sstop)>Go, and unsuccessful Stop-trials (Ustop)>Sstop between the three beverage
      groups enabled the identification of alcohol effects on functional neural
      circuits supporting inhibitory behaviour and error processing. Alcohol impaired
      inhibitory control as measured by the Stop-signal reaction time, but did not
      affect other aspects of VSST performance, nor performance on the VSST_C. The low
      alcohol dose evoked changes in neural activity within prefrontal, temporal,
      occipital and motor cortices. The high alcohol dose evoked changes in activity in
      areas affected by the low dose but importantly induced changes in activity within
      subcortical centres including the globus pallidus and thalamus. Alcohol did not
      affect neural correlates of perceptual processing of infrequent cues, as revealed
      by conjunction analyses of VSST and VSST_C tasks. Alcohol ingestion compromises
      the inhibitory control of action by modulating cortical regions supporting
      attentional, sensorimotor and action-planning processes. At higher doses the
      impact of alcohol also extends to affect subcortical nodes of fronto-basal
      ganglia- thalamo-cortical motor circuits. In contrast, alcohol appears to have
      little impact on the early visual processing of infrequent perceptual cues. These
      observations clarify clinically-important effects of alcohol on behaviour.

PMID- 24086759
TI  - A humanized monoclonal antibody specific for invariant Natural Killer T (iNKT)
      cells for in vivo depletion.
AB  - Invariant Natural Killer T (iNKT) cells are a subset of T cells recognizing
      glycolipid antigens presented by CD1d. Human iNKT cells express a conserved T
      cell receptor (TCR)-alpha chain (Valpha24-Jalpha18) paired with a specific beta
      chain, Vbeta11. The cells are both innate-like, with rapid cytokine release, and
      adaptive-like, including thymic positive selection. Over activation of iNKT cells
      can mediate tissue injury and inflammation in multiple organ systems and play a
      role in mediating the pathology associated with clinically important inflammatory
      diseases. At the same time, iNKT cell activation can play a role in protecting
      against infectious disease and cancer or modulate certain autoimmune diseases
      through its impact on both the innate and adaptive immune system. This suggests
      that approaches to cause iNKT cell reduction and/or depletion could treat
      inflammatory diseases while approaches to promote activation may have therapeutic
      potential in certain infections, cancer or autoimmune disease. This report
      summarizes the characterization of a humanized monoclonal depleting antibody
      (NKTT120) in the cynomolgus macaque. NKTT120 is being developed to treat iNKT
      mediated inflammation that is associated with chronic inflammatory conditions
      like sickle cell disease and asthma. NKTT120 binds to human iTCRs and to
      FCgammaRI and FCgammaRIII and has been shown to kill target cells in an ADCC
      assay at low concentrations consistent with the FCgammaR binding. iNKT cells were
      depleted within 24 hours in cynomolgus macaques, but T cell, B cell, and NK cell
      frequencies were unchanged. iNKT cell recovery was dose and time dependent. T
      cell dependent antigen responses were not impaired by NKTT120 mediated iNKT
      depletion as measured by response to KLH challenge. NKTT120 administration did
      not induce an inflammatory cytokine release at doses up to 10 mg/kg. These data
      support the use of NKTT120 as an intervention in inflammatory diseases where iNKT
      reduction or depletion could be beneficial. 

PMID- 24086760
TI  - Chemokine co-receptor CCR5/CXCR4-dependent modulation of Kv2.1 channel confers
      acute neuroprotection to HIV-1 glycoprotein gp120 exposure.
AB  - Infection with human immunodeficiency virus-1 (HIV-1) within the brain has long
      been known to be associated with neurodegeneration and neurocognitive disorder
      (referred as HAND), a condition characterized in its early stages by declining
      cognitive function and behavioral disturbances. Mechanistically, the HIV-1 coat
      glycoprotein 120 (gp120) has been suggested to be a critical factor inducing
      apoptotic cell death in neurons via the activation of p38 mitogen-activated
      protein kinase (MAPK), upon chronic exposure to the virus. Here we show that
      acute exposure of neurons to HIV-1 gp120 elicits a homeostatic response, which
      provides protection against non-apoptotic cell death, involving the major
      somatodendritic voltage-gated K+ (Kv) channel Kv2.1 as the key mediator. The
      Kv2.1 channel has recently been shown to provide homeostatic control of neuronal
      excitability under conditions of seizures, ischemia and
      neuromodulation/neuroinflammation. Following acute exposure to gp120, cultured
      rat hippocampal neurons show rapid dephosphorylation of the Kv2.1 protein, which
      ultimately leads to changes in specific sub-cellular localization and voltage
      dependent channel activation properties of Kv2.1. Such modifications in Kv2.1 are
      dependent on the activation of the chemokine co-receptors CCR5 and CXCR4, and
      subsequent activation of the protein phosphatase calcineurin. This leads to the
      overall suppression of neuronal excitability and provides neurons with a
      homeostatic protective mechanism. Specific blockade of calcineurin and Kv2.1
      channel activity led to significant enhancement of non-apoptotic neuronal death
      upon acute gp120 treatment. These observations shed new light on the intrinsic
      homeostatic mechanisms of neuronal resilience during the acute stages of neuro
      HIV infections.

PMID- 24086761
TI  - Comparative genomic analysis indicates that niche adaptation of terrestrial
      Flavobacteria is strongly linked to plant glycan metabolism.
AB  - Flavobacteria are important members of aquatic and terrestrial bacterial
      communities, displaying extreme variations in lifestyle, geographical
      distribution and genome size. They are ubiquitous in soil, but are often strongly
      enriched in the rhizosphere and phyllosphere of plants. In this study, we
      compared the genome of a root-associated Flavobacterium that we recently
      isolated, physiologically characterized and sequenced, to 14 additional
      Flavobacterium genomes, in order to pinpoint characteristics associated with its
      high abundance in the rhizosphere. Interestingly, flavobacterial genomes vary in
      size by approximately two-fold, with terrestrial isolates having predominantly
      larger genomes than those from aquatic environments. Comparative functional gene
      analysis revealed that terrestrial and aquatic Flavobacteria generally segregated
      into two distinct clades. Members of the aquatic clade had a higher ratio of
      peptide and protein utilization genes, whereas members of the terrestrial clade
      were characterized by a significantly higher abundance and diversity of genes
      involved in metabolism of carbohydrates such as xylose, arabinose and pectin.
      Interestingly, genes encoding glycoside hydrolase (GH) families GH78 and GH106,
      responsible for rhamnogalacturonan utilization (exclusively associated with
      terrestrial plant hemicelluloses), were only present in terrestrial clade
      genomes, suggesting adaptation of the terrestrial strains to plant-related
      carbohydrate metabolism. The Peptidase/GH ratio of aquatic clade Flavobacteria
      was significantly higher than that of terrestrial strains (1.7+/-0.7 and 9.7+/
      4.7, respectively), supporting the concept that this relation can be used to
      infer Flavobacterium lifestyles. Collectively, our research suggests that
      terrestrial Flavobacteria are highly adapted to plant carbohydrate metabolism,
      which appears to be a key to their profusion in plant environments. 

PMID- 24086763
TI  - Discerning the subfibrillar structure of mineralized collagen fibrils: a model
      for the ultrastructure of bone.
AB  - Biomineralization templated by organic molecules to produce inorganic-organic
      nanocomposites is a fascinating example of nature using bottom-up strategies at
      nanoscale to accomplish highly ordered multifunctional materials. One such
      nanocomposite is bone, composed primarily of hydroxyapatite (HA) nanocrystals
      that are embedded within collagen fibrils with their c-axes arranged roughly
      parallel to the long axis of the fibrils. Here we discern the ultra-structure of
      biomimetic mineralized collagen fibrils (MCFs) as consisting of bundles of
      subfibrils with approximately 10 nm diameter; each one with an organic-inorganic
      core-shell structure. Through an amorphous calcium phosphate precursor phase the
      HA nanocrystals were specifically grown along the longitudinal direction of the
      collagen microfibrils and encapsulated them within the crystal lattice. They
      intercalated throughout the collagen fibrils such that the mineral phase
      surrounded the surface of collagen microfibrils forming an interdigitated
      network. It appears that this arrangement of collagen microfibrils in collagen
      fibrils is responsible for the observed ultrastructure. Such a subfibrillar
      nanostructure in MCFs was identified in both synthetic and natural bone,
      suggesting this is the basic building block of collagen-based hard tissues.
      Insights into the ultrastructure of mineralized collagen fibrils have the
      potential to advance our understanding on the biomineralization principles and
      the relationship between bone's structure and mechanical properties, including
      fracture toughness mechanisms. We anticipate that these principles from
      biological systems can be applied to the rational design of new nanocomposites
      with improved performance. 

PMID- 24086762
TI  - Closely related influenza viruses induce contrasting respiratory tract
      immunopathology.
AB  - The swine-origin H1N1 virus which emerged in 2009 resulted in the first influenza
      pandemic of the 21(st) century. Although the majority of infections were
      moderate, a significant proportion of infections were severe and characterized by
      acute respiratory distress syndrome and pulmonary edema. We compared two isolates
      from the 2009 H1N1 pandemic; A/California/07/09 (CA/07) and A/Netherlands/602/09
      (NL/602) viruses that share greater than 99% sequence identity. Though
      genetically similar, these viruses exhibit contrasting pathological effects. Mice
      that were infected with 800 plaque forming unit (PFU) of CA/07 virus rapidly lost
      weight, which was concurrent with detection of high pulmonary concentrations of
      MCP-1, MIG, IP-10 and TIMP-1. Initially, severe bronchiolar epithelial necrosis
      and acute respiratory distress was observed, followed by marked bronchiolar
      epithelial hyperplasia. Mononuclear cell infiltration was initially localized to
      perivascular and peribronchiolar interstitium and then spread to adjacent
      alveoli. Infiltrating cells were phenotypically CD11b(hi), F4/80(lo). In
      contrast, when mice were infected with 800 PFU of NL/602 virus, minimal weight
      loss was observed, and concentrations of cytokines in the lung were significantly
      lower. Inflammation was primarily restricted to the bronchioles and perivascular
      interstitium with minimal spread to alveoli. Infiltrating cells include foamy
      macrophages and surface markers were characterized as CD11b(lo/-), F4/80(hi).
      These two genetically similar viruses can be useful strains with which to
      investigate immune-regulatory determinants of pathogenesis of influenza virus.

PMID- 24086764
TI  - The potential of metatranscriptomics for identifying screening targets for
      bacterial vaginosis.
AB  - BACKGROUND: The ribosomal RNA content of a sample collected from a woman with
      bacterial vaginosis (BV) was analysed to determine the active microbial
      community, and to identify potential targets for further screening.
      METHODOLOGY/PRINCIPAL FINDINGS: The sample from the BV patient underwent total
      RNA extraction, followed by physical subtraction of human rRNA and whole
      transcriptome amplification. The metatranscriptome was sequenced using Roche 454
      titanium chemistry. The bioinformatics pipeline MG-RAST and desktop DNA analysis
      platforms were utilised to analyse results. Bacteria of the genus Prevotella
      (predominately P. amnii) constituted 36% of the 16S rRNA reads, followed by
      Megasphaera (19%), Leptotrichia/Sneathia (8%) and Fusobacterium (8%). Comparison
      of the abundances of several bacteria to quantitative PCR (qPCR) screening of
      extracted DNA revealed comparable relative abundances. This suggests a
      correlation between what was present and transcriptionally active in this sample:
      however distinct differences were seen when compared to the microbiome determined
      by 16S rRNA gene amplicon sequencing. To assess the presence of P. amnii in a
      larger pool of samples, 90 sexually active women were screened using qPCR. This
      bacterium was found to be strongly associated with BV (P<0.001, OR 23.3
      (95%CI:2.9-190.7)) among the 90 women. CONCLUSIONS/SIGNIFICANCE: This study
      highlighted the potential of metatranscriptomics as a tool for characterising
      metabolically active microbiota and identifying targets for further screening.
      Prevotella amnii was chosen as an example target, being the most metabolically
      active species present in the single patient with BV, and was found to be
      detected at a high concentration by qPCR in 31% of cohort with BV, with an
      association with both oral and penile-vaginal sex.

PMID- 24086765
TI  - Knowledge of HBV and HCV and individuals' attitudes toward HBV- and HCV-infected
      colleagues: a national cross-sectional study among a working population in Japan.
AB  - Prejudice and discrimination in the workplace regarding the risk of transmission
      of Hepatitis B virus (HBV) and Hepatitis C virus (HCV) are increased by excess
      concerns due to a lack of relevant knowledge. Education to increase knowledge
      about HBV and HCV and their prevention could be the first step to reduce
      prejudice and discrimination. This study aimed to determine the association
      between the level of knowledge and negative attitudes toward HBV- and HCV
      infected colleagues among the Japanese working population. An online anonymous
      nationwide survey involving about 3,000 individuals was conducted in Japan. The
      questionnaire consisted of knowledge of HBV and HCV, and attitudes toward HBV-
      and HCV-infected colleagues in the workplace. Knowledge was divided into three
      categories: "ensuring daily activities not to be infected"; "risk of infection";
      and "characteristics of HBV/HCV hepatitis", based on the result of factor
      analysis. Multiple logistic regression analysis was applied. A total of 3,129
      persons responded to the survey: 36.0% reported they worried about the
      possibility of transmission of HBV and HCV from infected colleagues; 32.1%
      avoided contact with infected colleagues; and 23.7% had prejudiced opinions about
      HBV and HCV infection. The participants were classified into tertiles. A higher
      level of knowledge of HBV and HCV was significantly associated with these three
      negative attitudes (P for trend < 0.005). This study suggests that increasing
      knowledge may decrease individuals' negative attitudes towards HBV- and HCV
      infected colleagues. Thus, we should promote increased knowledge of HBV and HCV
      in stages to reduce negative attitudes toward HBV- and HCV-infected colleagues. 

PMID- 24086766
TI  - Reactive oxygen species are required for 5-HT-induced transactivation of neuronal
      platelet-derived growth factor and TrkB receptors, but not for ERK1/2 activation.
AB  - High concentrations of reactive oxygen species (ROS) induce cellular damage,
      however at lower concentrations ROS act as intracellular second messengers. In
      this study, we demonstrate that serotonin (5-HT) transactivates the platelet
      derived growth factor (PDGF) type beta receptor as well as the TrkB receptor in
      neuronal cultures and SH-SY5Y cells, and that the transactivation of both
      receptors is ROS-dependent. Exogenous application of H2O2 induced the
      phosphorylation of these receptors in a dose-dependent fashion, similar to that
      observed with 5-HT. However the same concentrations of H2O2 failed to increase
      ERK1/2 phosphorylation. Yet, the NADPH oxidase inhibitors diphenyleneiodonium
      chloride and apocynin blocked both 5-HT-induced PDGFbeta receptor phosphorylation
      and ERK1/2 phosphorylation. The increases in PDGFbeta receptor and ERK1/2
      phosphorylation were also dependent on protein kinase C activity, likely acting
      upstream of NADPH oxidase. Additionally, although the ROS scavenger N-acetyl-l
      cysteine abrogated 5-HT-induced PDGFbeta and TrkB receptor transactivation, it
      was unable to prevent 5-HT-induced ERK1/2 phosphorylation. Thus, the divergence
      point for 5-HT-induced receptor tyrosine kinase (RTK) transactivation and ERK1/2
      phosphorylation occurs at the level of NADPH oxidase in this system. The ability
      of 5-HT to induce the production of ROS resulting in transactivation of both
      PDGFbeta and TrkB receptors may suggest that instead of a single GPCR to single
      RTK pathway, a less selective, more global RTK response to GPCR activation is
      occurring.

PMID- 24086767
TI  - Effect of selectively introducing arginine and D-amino acids on the antimicrobial
      activity and salt sensitivity in analogs of human beta-defensins.
AB  - We have examined the antimicrobial activity of C-terminal analogs of human beta
      defensins HBD-1 and-3 wherein lysines have been selectively replaced by L- and D
      arginines and L-isoleucine substituted with its D-enantiomer. The analogs
      exhibited antibacterial and antifungal activities. Physiological concentration of
      NaCl did not attenuate the activity of the peptides against Gram-negative
      bacteria considerably, while some attenuation of activity was observed against S.
      aureus. Variable attenuation of activity was observed in the presence of Ca2+ and
      Mg2+. Introduction of D-amino acids abrogated the need for a disulfide bridge for
      exhibiting activity. Confocal images of carboxyfluorescein (CF) labeled peptides
      indicated initial localization on the membrane and subsequent translocation into
      the cell. Analogs corresponding to cationic rich segments of human defensins
      substituted with L- and D-arginine, could be attractive candidates for
      development as future therapeutic drugs.

PMID- 24086768
TI  - Positional information is reprogrammed in blastema cells of the regenerating limb
      of the axolotl (Ambystoma mexicanum).
AB  - The regenerating region of an amputated salamander limb, known as the blastema,
      has the amazing capacity to replace exactly the missing structures. By grafting
      cells from different stages and regions of blastemas induced to form on donor
      animals expressing Green Fluorescent Protein (GFP), to non-GFP host animals, we
      have determined that the cells from early stage blastemas, as well as cells at
      the tip of late stage blastemas are developmentally labile such that their
      positional identity is reprogrammed by interactions with more proximal cells with
      stable positional information. In contrast, cells from the adjacent, more
      proximal stump tissues as well as the basal region of late bud blastemas are
      positionally stable, and thus form ectopic limb structures when grafted. Finally,
      we have found that a nerve is required to maintain the blastema cells in a
      positionally labile state, thus indicating a role for reprogramming cues in the
      blastema microenvironment. 

PMID- 24086769
TI  - Genetic alterations within the DENND1A gene in patients with polycystic ovary
      syndrome (PCOS).
AB  - Polycystic ovary syndrome (PCOS), the most common endocrine disease among
      premenopausal women, is caused by both genes and environment. We and others
      previously reported association between single nucleotide polymorphisms (SNPs) in
      the DENND1A gene and PCOS. We therefore sequenced the DENND1A gene in white
      patients with PCOS to identify possible alterations that may be implicated in the
      PCOS pathogenesis. Patients were referred with PCOS and/or hirsutism between 1998
      and 2011 (n = 261). PCOS was diagnosed according to the Rotterdam criteria (n =
      165). Sequence analysis was performed in 10 patients with PCOS. Additional
      patients (n = 251) and healthy female controls (n = 248) were included for SNP
      genotyping. Patients underwent clinical examination including Ferriman-Gallwey
      score (FG-score), biochemical analyses and transvaginal ultrasound. Mutation
      analysis was carried out by bidirectional sequencing. SNP genotyping was tested
      by allelic discrimination in real-time PCR in the additional patients and
      controls. Sequencing of the DENND1A gene identified eight SNPs; seven were not
      known to be associated with any diseases. One missense SNP was detected
      (rs189947178, A/C), potentially altering the structural conformation of the
      DENND1A protein. SNP genotyping of rs189947178 showed significantly more carriers
      among patients with PCOS and moderate hirsutism compared to controls. However,
      due to small sample size and lack of multiple regression analysis supporting an
      association between rs189947178 and FG-score or PCOS diagnosis, this could be a
      false positive finding. In conclusion, sequence analysis of the DENND1A gene of
      patients with PCOS did not identify alterations that alone could be responsible
      for the PCOS pathogenesis, but a missense SNP (rs189947178) was identified in one
      patient and significantly more carriers of rs189947178 were found among patients
      with PCOS and moderate hirsutism vs. controls. Additional studies with
      independent cohort are needed to confirm this due to the small sample size of
      this study. 

PMID- 24086770
TI  - Combination of phagostimulant and visual lure as an effective tool in designing
      house fly toxic baits: a laboratory evaluation.
AB  - House flies (Diptera: Muscidae), potential vectors of a variety of pathogens,
      characteristically search and feed on sugar sources just after emergence for
      their survival. Phagostimulants like sugars, and visual characteristics of
      feeding materials play an important role in foraging success in house flies.
      Therefore, development of toxic baits by using the combination of phagostimulant
      and visual lure may prove effective in localized control of house flies. In the
      present study, visual attraction of house flies to different fabric colors was
      studied in choice and no choice experiments. Dark blue was the most preferred
      color in both experiments. In toxicity experiments, insecticide solutions were
      prepared in 20% sugar solution. Dark blue fabric strips were prepared by
      moistening with 20% sugar water solution containing median lethal concentrations
      of one of the four insecticides viz., fipronil, Imidacloprid, indoxacarb and
      Spinosad. The fabric strips treated with fipronil and Imidacloprid took minimum
      time (7.66 and 7.81 h, respectively) to cause 50% mortality, while those treated
      with Spinosad and indoxacarb took relatively more time (13.62 and 17.91 h,
      respectively) to cause 50% mortality. In conclusion, the combination of
      phagostimulant and visual lure could be used in designing toxic baits for house
      flies. 

PMID- 24086771
TI  - Synergistic effects of celecoxib and bupropion in a model of chronic inflammation
      related depression in mice.
AB  - This study was aimed to characterize the depression-like behaviour in the
      classical model of chronic inflammation induced by Complete Freund's Adjuvant
      (CFA). Male Swiss mice received an intraplantar (i.pl.) injection of CFA (50
      ul/paw) or vehicle. Behavioural and inflammatory responses were measured at
      different time-points (1 to 4 weeks), and different pharmacological tools were
      tested. The brain levels of IL-1beta and BDNF, or COX-2 expression were also
      determined. CFA elicited a time-dependent edema formation and mechanical
      allodynia, which was accompanied by a significant increase in the immobility time
      in the tail suspension (TST) or forced-swimming (FST) depression tests. Repeated
      administration of the antidepressants imipramine (10 mg/kg), fluoxetine (20
      mg/kg) and bupropion (30 mg/kg) significantly reversed depression-like behaviour
      induced by CFA. Predictably, the anti-inflammatory drugs dexamethasone (0.5
      mg/kg), indomethacin (10 mg/kg) and celecoxib (30 mg/kg) markedly reduced CFA
      induced edema. The oral treatment with the analgesic drugs dipyrone (30 and 300
      mg/kg) or pregabalin (30 mg/kg) significantly reversed the mechanical allodyinia
      induced by CFA. Otherwise, either dipyrone or pregabalin (both 30 mg/kg) did not
      significantly affect the paw edema or the depressive-like behaviour induced by
      CFA, whereas the oral treatment with dipyrone (300 mg/kg) was able to reduce the
      immobility time in TST. Noteworthy, CFA-induced edema was reduced by bupropion
      (30 mg/kg), and depression behaviour was prevented by celecoxib (30 mg/kg). The
      co-treatment with bupropion and celecoxib (3 mg/kg each) significantly inhibited
      both inflammation and depression elicited by CFA. The same combined treatment
      reduced the brain levels of IL-1beta, as well as COX-2 immunopositivity, whilst
      it failed to affect the reduction of BDNF levels. We provide novel evidence on
      the relationship between chronic inflammation and depression, suggesting that
      combination of antidepressant and anti-inflammatory agents bupropion and
      celecoxib might represent an attractive therapeutic strategy for depression. 

PMID- 24086772
TI  - System for stable beta-estradiol-inducible gene expression in the moss
      Physcomitrella patens.
AB  - Inducible transgene expression provides a useful tool to analyze gene function.
      The moss Physcomitrellapatens is a model basal land plant with well-developed
      research tools, including a high efficiency of gene targeting and substantial
      genomics resources. However, current systems for controlled transgene expression
      remain limited. Here we report the development of an estrogen receptor mediated
      inducible gene expression system, based on the system used in flowering plants.
      After identifying the appropriate promoters to drive the chimeric transducer, we
      succeeded in inducing transcription over 1,000-fold after 24 h incubation with
      beta-estradiol. The P. patens system was also effective for high-level long-term
      induction of gene expression; transcript levels of the activated gene were
      maintained for at least seven days on medium containing beta-estradiol. We also
      established two potentially neutral targeting sites and a set of vectors for
      reproducible expression of two transgenes. This beta-estradiol-dependent system
      will be useful to test genes individually or in combination, allowing stable,
      inducible transgenic expression in P. patens.

PMID- 24086773
TI  - Arabidopsis clade I TGA factors regulate apoplastic defences against the
      bacterial pathogen Pseudomonas syringae through endoplasmic reticulum-based
      processes.
AB  - During the plant immune response, large-scale transcriptional reprogramming is
      modulated by numerous transcription (co) factors. The Arabidopsis basic leucine
      zipper transcription factors TGA1 and TGA4, which comprise the clade I TGA
      factors, have been shown to positively contribute to disease resistance against
      virulent strains of the bacterial pathogen Pseudomonas syringae. Despite
      physically interacting with the key immune regulator, NON-EXPRESSOR OF
      PATHOGENESIS-RELATED GENES 1 (NPR1), following elicitation with salicylic acid
      (SA), clade I function was shown to be largely independent of NPR1. Unlike
      mutants in NPR1, tga1-1 tga4-1 plants do not display reductions in steady-state
      levels of SA-pathway marker genes following treatment with this phenolic
      signaling metabolite or after challenge with virulent or avirulent P. syringae.
      By exploiting bacterial strains that have limited capacity to suppress
      Arabidopsis defence responses, the present study demonstrates that tga1-1 tga4-1
      plants are compromised in basal resistance and defective in several apoplastic
      defence responses, including the oxidative burst of reactive oxygen species,
      callose deposition, as well as total and apoplastic PATHOGENESIS-RELATED 1 (PR-1)
      protein accumulation. Furthermore, analysis of npr1-1 and the tga1-1 tga4-1 npr1
      1 triple mutant indicates that clade I TGA factors act substantially independent
      of NPR1 in mediating disease resistance against these strains of P. syringae.
      Increased sensitivity to the N-glycosylation inhibitor tunicamycin and elevated
      levels of endoplasmic reticulum (ER) stress marker genes encoding ER-resident
      chaperones in mutant seedlings suggest that loss of apoplastic defence responses
      is associated with aberrant protein secretion and implicate clade I TGA factors
      as positive regulators of one or more ER-related secretion pathways. 

PMID- 24086774
TI  - Multivesicular release underlies short term synaptic potentiation independent of
      release probability change in the supraoptic nucleus.
AB  - Magnocellular neurons of the supraoptic nucleus receive glutamatergic excitatory
      inputs that regulate the firing activity and hormone release from these neurons.
      A strong, brief activation of these excitatory inputs induces a lingering barrage
      of tetrodotoxin-resistant miniature EPSCs (mEPSCs) that lasts for tens of
      minutes. This is known to accompany an immediate increase in large amplitude
      mEPSCs. However, it remains unknown how long this amplitude increase can last and
      whether it is simply a byproduct of greater release probability. Using in vitro
      patch clamp recording on acute rat brain slices, we found that a brief, high
      frequency stimulation (HFS) of afferents induced a potentiation of mEPSC
      amplitude lasting up to 20 min. This amplitude potentiation did not correlate
      with changes in mEPSC frequency, suggesting that it does not reflect changes in
      presynaptic release probability. Nonetheless, neither postsynaptic calcium
      chelator nor the NMDA receptor antagonist blocked the potentiation. Together with
      the known calcium dependency of HFS-induced potentiation of mEPSCs, our results
      imply that mEPSC amplitude increase requires presynaptic calcium. Further
      analysis showed multimodal distribution of mEPSC amplitude, suggesting that large
      mEPSCs were due to multivesicular glutamate release, even at late post-HFS when
      the frequency is no longer elevated. In conclusion, high frequency activation of
      excitatory synapses induces lasting multivesicular release in the SON, which is
      independent of changes in release probability. This represents a novel form of
      synaptic plasticity that may contribute to prolonged excitatory tone necessary
      for generation of burst firing of magnocellular neurons. 

PMID- 24086775
TI  - Advancing Sino-Indian cooperation to combat tropical diseases.

PMID- 24086776
TI  - Preparing for dengue vaccine introduction: recommendations from the 1st dengue
      v2V International Meeting.

PMID- 24086777
TI  - Mediational effects of self-efficacy dimensions in the relationship between
      knowledge of dengue and dengue preventive behaviour with respect to control of
      dengue outbreaks: a structural equation model of a cross-sectional survey.
AB  - BACKGROUND: Dengue fever is endemic in Malaysia, with frequent major outbreaks in
      urban areas. The major control strategy relies on health promotional campaigns
      aimed at encouraging people to reduce mosquito breeding sites close to people's
      homes. However, such campaigns have not always been 100% effective. The concept
      of self-efficacy is an area of increasing research interest in understanding how
      health promotion can be most effective. This paper reports on a study of the
      impact of self-efficacy on dengue knowledge and dengue preventive behaviour.
      METHODS AND FINDINGS: We recruited 280 adults from 27 post-outbreak villages in
      the state of Terengganu, east coast of Malaysia. Measures of health promotion and
      educational intervention activities and types of communication during outbreak,
      level of dengue knowledge, level and strength of self-efficacy and dengue
      preventive behaviour were obtained via face-to-face interviews and
      questionnaires. A structural equation model was tested and fitted the data well
      (chi(2) = 71.659, df = 40, p = 0.002, RMSEA = 0.053, CFI = 0.973, TLI = 0.963).
      Mass media, local contact and direct information-giving sessions significantly
      predicted level of knowledge of dengue. Level and strength of self-efficacy fully
      mediated the relationship between knowledge of dengue and dengue preventive
      behaviours. Strength of self-efficacy acted as partial mediator in the
      relationship between knowledge of dengue and dengue preventive behaviours.
      CONCLUSIONS: To control and prevent dengue outbreaks by behavioural measures,
      health promotion and educational interventions during outbreaks should now focus
      on those approaches that are most likely to increase the level and strength of
      self-efficacy.

PMID- 24086778
TI  - Factors associated with dengue shock syndrome: a systematic review and meta
      analysis.
AB  - BACKGROUND: The pathogenesis of dengue shock syndrome (DSS, grade 3 and 4) is not
      yet completely understood. Several factors are reportedly associated with DSS, a
      more severe form of dengue infection that reportedly causes 50 times higher
      mortality compared to that of dengue patients without DSS. However, the results
      from these reports remain inconclusive. To better understand the epidemiology,
      clinical manifestation, and pathogenesis of DSS for development of new therapy,
      we systematically reviewed and performed a meta-analysis of relevant studies that
      reported factors in both DSS and dengue hemorrhagic fever (DHF, grade 1 and 2)
      patients. METHODS AND FINDINGS: PubMed, EMBASE, Scopus, Google Scholar, Dengue
      Bulletin, Cochrane Library, Virtual Health Library, and a manual search of
      reference lists of articles published before September 2010 were used to retrieve
      relevant studies. A meta-analysis using fixed- or random-effects models was used
      to calculate pooled odds ratios (OR) or event rate with corresponding 95%
      confidence intervals. Assessment of heterogeneity and publication bias, meta
      regression analysis, subgroup analysis, sensitivity analysis, and analysis of
      factor-specific relationships were further performed. There were 198 studies
      constituting 203 data sets that met our eligibility criteria. Our meta-regression
      analysis showed a sustained reduction of DSS/dengue hemorrhagic fever (DHF) ratio
      over a period of 40 years in Southeast Asia, especially in Thailand. The meta
      analysis revealed that age, female sex, neurological signs, nausea/vomiting,
      abdominal pain, gastrointestinal bleeding, hemoconcentration, ascites, pleural
      effusion, hypoalbuminemia, hypoproteinemia, hepatomegaly, levels of alanine
      transaminase and aspartate transaminase, thrombocytopenia, prothrombin time,
      activated partial thromboplastin time, fibrinogen level, primary/secondary
      infection, and dengue virus serotype-2 were significantly associated with DSS
      when pooling all original relevant studies. CONCLUSIONS: The results improve our
      knowledge of the pathogenesis of DSS by identifying the association between the
      epidemiology, clinical signs, and biomarkers involved in DSS.

PMID- 24086779
TI  - Human T-cell lymphotropic virus type 1 subtype C molecular variants among
      indigenous australians: new insights into the molecular epidemiology of HTLV-1 in
      Australo-Melanesia.
AB  - BACKGROUND: HTLV-1 infection is endemic among people of Melanesian descent in
      Papua New Guinea, the Solomon Islands and Vanuatu. Molecular studies reveal that
      these Melanesian strains belong to the highly divergent HTLV-1c subtype. In
      Australia, HTLV-1 is also endemic among the Indigenous people of central
      Australia; however, the molecular epidemiology of HTLV-1 infection in this
      population remains poorly documented. FINDINGS: Studying a series of 23 HTLV-1
      strains from Indigenous residents of central Australia, we analyzed coding (gag,
      pol, env, tax) and non-coding (LTR) genomic proviral regions. Four complete HTLV
      1 proviral sequences were also characterized. Phylogenetic analyses implemented
      with both Neighbor-Joining and Maximum Likelihood methods revealed that all
      proviral strains belong to the HTLV-1c subtype with a high genetic diversity,
      which varied with the geographic origin of the infected individuals. Two distinct
      Australians clades were found, the first including strains derived from most
      patients whose origins are in the North, and the second comprising a majority of
      those from the South of central Australia. Time divergence estimation suggests
      that the speciation of these two Australian clades probably occurred 9,120 years
      ago (38,000-4,500). CONCLUSIONS: The HTLV-1c subtype is endemic to central
      Australia where the Indigenous population is infected with diverse subtype c
      variants. At least two Australian clades exist, which cluster according to the
      geographic origin of the human hosts. These molecular variants are probably of
      very ancient origin. Further studies could provide new insights into the
      evolution and modes of dissemination of these retrovirus variants and the
      associated ancient migration events through which early human settlement of
      Australia and Melanesia was achieved.

PMID- 24086780
TI  - Association between age and severity to leptospirosis in children.
AB  - BACKGROUND: In endemic areas, leptospirosis is more common and more severe in
      adults compared with children. Reasons to explain this discrepancy remain unclear
      and limited data focusing on adolescents are available. The objective of the
      study was to describe disease spectrum and outcome differences in children and
      adolescents admitted for leptospirosis in a large at-risk population. METHODS:
      Clinical and laboratory data were obtained on hospitalized cases in New Caledonia
      from 2006 to 2012. RESULTS: Data of 60 patients <18 years of age (25 children
      under 14 and 35 adolescents aged 14 to 17) with confirmed leptospirosis were
      analyzed. Compared with children, adolescents presented more often with classic
      features of Weil disease (p = 0.02), combining hepatic and renal involvement with
      or without pulmonary participation. Jarisch-Herxheimer reactions were observed
      more often among adolescents (p<0.01). The overall case fatality rate was low (1
      adolescent versus 0 children). CONCLUSION: Severe leptospirosis in adolescents
      may be more likely to show adults' characteristics compared with children.
      Further studies are required to explore age-dependant host factors, including
      puberty-related physiological changes.

PMID- 24086781
TI  - Integration of water, sanitation, and hygiene for the prevention and control of
      neglected tropical diseases: a rationale for inter-sectoral collaboration.
AB  - Improvements of water, sanitation, and hygiene (WASH) infrastructure and
      appropriate health-seeking behavior are necessary for achieving sustained
      control, elimination, or eradication of many neglected tropical diseases (NTDs).
      Indeed, the global strategies to fight NTDs include provision of WASH, but few
      programs have specific WASH targets and approaches. Collaboration between disease
      control programs and stakeholders in WASH is a critical next step. A group of
      stakeholders from the NTD control, child health, and WASH sectors convened in
      late 2012 to discuss opportunities for, and barriers to, collaboration. The group
      agreed on a common vision, namely "Disease-free communities that have adequate
      and equitable access to water and sanitation, and that practice good hygiene."
      Four key areas of collaboration were identified, including (i) advocacy, policy,
      and communication; (ii) capacity building and training; (iii) mapping, data
      collection, and monitoring; and (iv) research. We discuss strategic opportunities
      and ways forward for enhanced collaboration between the WASH and the NTD sectors.

PMID- 24086782
TI  - Validation of two rapid diagnostic tests for visceral leishmaniasis in Kenya.
AB  - BACKGROUND: Visceral leishmaniasis (VL) is a systemic parasitic disease that is
      fatal unless treated. In Kenya, national VL guidelines rely on microscopic
      examination of spleen aspirate to confirm diagnosis. As this procedure is
      invasive, it cannot be safely implemented in peripheral health structures, where
      non-invasive, accurate, easy to use diagnostic tests are needed. METHODOLOGY: We
      evaluated the sensitivity, specificity and predictive values of two rapid
      diagnostic tests (RDT), DiaMed IT LEISH and Signal-KA, among consecutive patients
      with clinical suspicion of VL in two treatment centres located in Baringo and
      North Pokot District, Rift Valley province, Kenya. Microscopic examination of
      spleen aspirate was the reference diagnostic standard. Patients were
      prospectively recruited between May 2010 and July 2011. PRINCIPAL FINDINGS: Of
      251 eligible patients, 219 patients were analyzed, including 131 VL and 88 non-VL
      patients. The median age of VL patients was 16 years with predominance of males
      (66%). None of the tested VL patients were co-infected with HIV. Sensitivity and
      specificity of the DiaMed IT LEISH were 89.3% (95%CI: 82.7-94%) and 89.8% (95%CI:
      81.5-95.2%), respectively. The Signal KA showed trends towards lower sensitivity
      (77.1%; 95%CI: 68.9-84%) and higher specificity (95.5%; 95%CI: 88.7-98.7%).
      Combining the tests did not improve the overall diagnostic performance, as all
      patients with a positive Signal KA were also positive with the DiaMed IT LEISH.
      CONCLUSION/SIGNIFICANCE: The DiaMed IT LEISH can be used to diagnose VL in Kenyan
      peripheral health facilities where microscopic examination of spleen aspirate or
      sophisticated serological techniques are not feasible. There is a crucial need
      for an improved RDT for VL diagnosis in East Africa.

PMID- 24086783
TI  - Spinal cystic echinococcosis--a systematic analysis and review of the literature:
      part 1. Epidemiology and anatomy.
AB  - Bone involvement in human cystic echinococcosis (CE) is rare, but affects the
      spine in approximately 50% of cases. Despite significant advances in diagnostic
      imaging techniques as well as surgical and medical treatment of spinal CE, our
      basic understanding of the parasite's predilection for the spine remains
      incomplete. To fill this gap, we systematically reviewed the published literature
      of the last five decades to summarize and analyze the currently existing data on
      epidemiological and anatomical aspects of spinal CE. 

PMID- 24086784
TI  - Microarray analysis of microbiota of gingival lesions in noma patients.
AB  - Noma (cancrum oris) is a gangrenous disease of unknown etiology affecting the
      maxillo-facial region of young children in extremely limited resource countries.
      In an attempt to better understand the microbiological events occurring during
      this disease, we used phylogenetic and low-density microarrays targeting the 16S
      rRNA gene to characterize the gingival flora of acute noma and acute necrotizing
      gingivitis (ANG) lesions, and compared them to healthy control subjects of the
      same geographical and social background. Our observations raise doubts about
      Fusobacterium necrophorum, a previously suspected causative agent of noma, as
      this species was not associated with noma lesions. Various oral pathogens were
      more abundant in noma lesions, notably Atopobium spp., Prevotella intermedia,
      Peptostreptococcus spp., Streptococcus pyogenes and Streptococcus anginosus. On
      the other hand, pathogens associated with periodontal diseases such as
      Aggregatibacter actinomycetemcomitans, Capnocytophaga spp., Porphyromonas spp.
      and Fusobacteriales were more abundant in healthy controls. Importantly, the
      overall loss of bacterial diversity observed in noma samples as well as its
      homology to that of ANG microbiota supports the hypothesis that ANG might be the
      immediate step preceding noma. 

PMID- 24086785
TI  - In silico identification of a candidate synthetic peptide (Tsgf118-43) to monitor
      human exposure to tsetse flies in West Africa.
AB  - BACKGROUND: The analysis of humoral responses directed against the saliva of
      blood-sucking arthropods was shown to provide epidemiological biomarkers of human
      exposure to vector-borne diseases. However, the use of whole saliva as antigen
      presents several limitations such as problems of mass production, reproducibility
      and specificity. The aim of this study was to design a specific biomarker of
      exposure to tsetse flies based on the in silico analysis of three Glossina
      salivary proteins (Ada, Ag5 and Tsgf1) previously shown to be specifically
      recognized by plasma from exposed individuals. METHODOLOGY/PRINCIPAL FINDINGS:
      Synthetic peptides were designed by combining several linear epitope prediction
      methods and Blast analysis. The most specific peptides were then tested by
      indirect ELISA on a bank of 160 plasma samples from tsetse infested areas and
      tsetse free areas. Anti-Tsgf118-43 specific IgG levels were low in all three
      control populations (from rural Africa, urban Africa and Europe) and were
      significantly higher (p<0.0001) in the two populations exposed to tsetse flies
      (Guinean HAT foci, and South West Burkina Faso). A positive correlation was also
      found between Anti-Tsgf118-43 IgG levels and the risk of being infected by
      Trypanosoma brucei gambiense in the sleeping sickness foci of Guinea.
      CONCLUSION/SIGNIFICANCE: The Tsgf118-43 peptide is a suitable and promising
      candidate to develop a standardize immunoassay allowing large scale monitoring of
      human exposure to tsetse flies in West Africa. This could provide a new
      surveillance indicator for tsetse control interventions by HAT control programs.

PMID- 24086786
TI  - Local immune responses of the Chinese water buffalo, Bubalus bubalis, against
      Schistosoma japonicum larvae: crucial insights for vaccine design.
AB  - Asian schistosomiasis is a zoonotic parasitic disease infecting up to a million
      people and threatening tens of millions more. Control of this disease is hindered
      by the animal reservoirs of the parasite, in particular the water buffalo
      (Bubalus bubalis), which is responsible for significant levels of human
      transmission. A transmission-blocking vaccine administered to buffaloes is a
      realistic option which would aid in the control of schistosomiasis. This will
      however require a better understanding of the immunobiology of schistosomiasis in
      naturally exposed buffaloes, particularly the immune response to migrating
      schistosome larvae, which are the likely targets of an anti-schistosome vaccine.
      To address this need we investigated the immune response at the major sites of
      larval migration, the skin and the lungs, in previously exposed and re-challenged
      water buffaloes. In the skin, a strong allergic-type inflammatory response
      occurred, characterised by leukocyte and eosinophil infiltration including the
      formation of granulocytic abscesses. Additionally at the local skin site,
      interleukin-5 transcript levels were elevated, while interleukin-10 levels
      decreased. In the skin-draining lymph node (LN) a predominant type-2 profile was
      seen in stimulated cells, while in contrast a type-1 profile was detected in the
      lung draining LN, and these responses occurred consecutively, reflecting the
      timing of parasite migration. The intense type-2 immune response at the site of
      cercarial penetration is significantly different to that seen in naive and
      permissive animal models such as mice, and suggests a possible mechanism for
      immunity. Preliminary data also suggest a reduced and delayed immune response
      occurred in buffaloes given high cercarial challenge doses compared with moderate
      infections, particularly in the skin. This study offers a deeper understanding
      into the immunobiology of schistosomiasis in a natural host, which may aid in the
      future design of more effective vaccines. 

PMID- 24086787
TI  - Impact of neutrophil-secreted myeloid related proteins 8 and 14 (MRP 8/14) on
      leishmaniasis progression.
AB  - The myeloid-related proteins (MRPs) 8/14 are small proteins mainly produced by
      neutrophils, which have been reported to induce NO production in macrophages. On
      the other hand, Leishmania survives and multiplies within phagocytes by
      inactivating several of their microbicidal functions. Whereas MRPs are rapidly
      released during the innate immune response, their role in the regulation of
      Leishmaniasis is still unknown. In vitro experiments revealed that Leishmania
      infection alters MRP-induced signaling, leading to inhibition of macrophage
      functions (NO, TNF-alpha). In contrast, MRP-primed cells showed normal signaling
      activation and NO production in response to Leishmania infection. Using a murine
      air-pouch model, we observed that infection with L. major induced leukocyte
      recruitment and MRP secretion comparable to LPS-treated mice. Depletion of MRPs
      significantly reduced these inflammatory events and augmented both parasite load
      and footpad swelling during the first 8 weeks post-infection, as also observed in
      MRP KO mice. On the contrary, mouse treatment with recombinant MRPs (rMRPs) had
      the opposite effect. Collectively, our results suggest that rapid secretion of
      MRPs by neutrophils at the site of infection may protect uninfected macrophages
      and favor a more efficient innate inflammatory response against Leishmania
      infection. In summary, our study reveals the critical role played by MRPs in the
      regulation of Leishmania infection and how this pathogen can subvert its action. 

PMID- 24086788
TI  - The Nicaraguan pediatric dengue cohort study: incidence of inapparent and
      symptomatic dengue virus infections, 2004-2010.
AB  - Dengue, caused by the four serotypes of dengue virus (DENV), is the most
      prevalent mosquito-borne viral disease of humans. To examine the incidence and
      transmission of dengue, the authors performed a prospective community-based
      cohort study in 5,545 children aged 2-14 years in Managua, Nicaragua, between
      2004 and 2010. Children were provided with medical care through study physicians
      who systematically recorded medical consult data, and yearly blood samples were
      collected to evaluate DENV infection incidence. The incidence of dengue cases
      observed was 16.1 cases (range 3.4-43.5) per 1,000 person-years (95% CI: 14.5,
      17.8), and a pattern of high dengue case incidence every other year was observed.
      The incidence of DENV infections was 90.2 infections (range 45.2-105.3) per 1,000
      person-years (95% CI: 86.1, 94.5). The majority of DENV infections in young
      children (<6 years old) were primary (60%) and the majority of infections in
      older children (>= 9 years of age) were secondary (82%), as expected. The
      incidence rate of second DENV infections (121.3 per 1,000 person-years; 95% CI:
      102.7, 143.4) was significantly higher than the incidence rate of primary DENV
      infections (78.8 per 1,000 person-years; 95% CI: 73.2, 84.9). The rigorous
      analytic methodology used in this study, including incidence reporting in person
      years, allows comparison across studies and across different infectious diseases.
      This study provides important information for understanding dengue epidemiology
      and informing dengue vaccine policy.

PMID- 24086789
TI  - Development of assays using hexokinase and phosphoglucomutase gene sequences that
      distinguish strains of Leishmania tropica from different zymodemes and
      microsatellite clusters and their application to Palestinian foci of cutaneous
      leishmaniasis.
AB  - BACKGROUND/OBJECTIVES: Palestinian strains of L.tropica characterized by
      multilocus enzyme electrophoresis (MLEE) fall into two zymodemes, either MON-137
      or MON-307. METHODOLOGY/PRINCIPLE FINDINGS: Assays employing PCR and subsequent
      RFLP were applied to sequences found in the Hexokinase (HK) gene, an enzyme that
      is not used in MLEE, and the Phosphoglucomutase (PGM) gene, an enzyme that is
      used for MLEE, to see if they would facilitate consigning local strains of
      L.tropica to either zymodeme MON-137 or zymodeme MON-307. Following amplification
      and subsequent double digestion with the restriction endonucleases MboI and
      HaeIII, variation in the restriction patterns of the sequence from the HK gene
      distinguished strains of L.tropica, L.major and L.infantum and also exposed two
      genotypes (G) among the strains of L.tropica: HK-LtG1, associated with strains of
      L.tropica of the zymodemes MON-137 and MON-265, and HK-LtG2, associated with
      strains of L.tropica of the zymodemes MON-307, MON-288, MON-275 and MON-54.
      Following amplification and subsequent digestion by the restriction endonuclease
      MboI, variation in the sequence from the PGM gene also exposed two genotypes
      among the strains of L.tropica: PGM-G1, associated only with strains of L.tropica
      of the zymodeme MON-137; and PGM-G2, associated with strains of L.tropica of the
      zymodemes MON-265, MON-307, MON-288, MON-275 and MON-54, and, also, with six
      strains of L.major, five of L.infantum and one of L.donovani. The use of the HK
      and PGM gene sequences enabled distinction the L.tropica strains of the zymodeme
      MON-137 from those of the zymodeme MON-265. This genotyping system 'correctly'
      identified reference strains of L.tropica of known zymodemal affiliation and also
      from clinical samples, with a level of sensitivity down to <1 fg in the case of
      the former and to 1 pg of DNA in the case of the latter.
      CONCLUSIONS/SIGNIFICANCE: Both assays proved useful for identifying leishmanial
      parasites in clinical samples without resource to culture and MLEE.

PMID- 24086790
TI  - Eco-bio-social determinants for house infestation by non-domiciliated Triatoma
      dimidiata in the Yucatan Peninsula, Mexico.
AB  - BACKGROUND: Chagas disease is a vector-borne disease of major importance in the
      Americas. Disease prevention is mostly limited to vector control. Integrated
      interventions targeting ecological, biological and social determinants of vector
      borne diseases are increasingly used for improved control. METHODOLOGY/PRINCIPAL
      FINDINGS: We investigated key factors associated with transient house infestation
      by T. dimidiata in rural villages in Yucatan, Mexico, using a mixed modeling
      approach based on initial null-hypothesis testing followed by multimodel
      inference and averaging on data from 308 houses from three villages. We found
      that the presence of dogs, chickens and potential refuges, such as rock piles, in
      the peridomicile as well as the proximity of houses to vegetation at the
      periphery of the village and to public light sources are major risk factors for
      infestation. These factors explain most of the intra-village variations in
      infestation. CONCLUSIONS/SIGNIFICANCE: These results underline a process of
      infestation distinct from that of domiciliated triatomines and may be used for
      risk stratification of houses for both vector surveillance and control. Combined
      integrated vector interventions, informed by an Ecohealth perspective, should aim
      at targeting several of these factors to effectively reduce infestation and
      provide sustainable vector control.

PMID- 24086791
TI  - Commentary by Spear, R. on "Integration of water, sanitation, and hygiene for the
      prevention and control of neglected tropical diseases: a rationale for inter
      sectoral collaboration:" can the control of NTDs profit from a good WASH?

PMID- 24086792
TI  - A rare presentation of an intraosseous lipoma in the proximal femur.
AB  - PATIENT: Female, 32 FINAL DIAGNOSIS: Intraosseous lipoma Symptoms: Swelling of
      the thigh Medication: - Clinical Procedure: Excision of the mass Specialty:
      Surgery. OBJECTIVE: Rare disease. BACKGROUND: Intraosseous lipomas happen to be
      one of rarest benign soft tissue tumors with only a little known about its
      etiology and pathophysiology. A pubmed search using key word "Intraosseous
      lipoma". Came back with 165 results. All the sizes and presentations were
      reviewed and compared with the case we are presenting. We are reporting a 15*20
      cm intraosseous lipoma. CASE REPORT: 32-year-old lady with a large intraosseous
      lipoma in the proximal thigh. The largest reported in English literature.
      CONCLUSIONS: A intraosseous lesion with this size could still be benign even if
      its lager than 5 cm. Keeping in mind that with a lesion this size malignancy
      should always be ruled out.

PMID- 24086793
TI  - Bland-White-Garland syndrome - a rare and serious cause of failure to thrive.
AB  - PATIENT: Male, 0 FINAL DIAGNOSIS: Bland-White-Garland syndrome Symptoms:
      Cardiomegaly, feeding problems Medication: - Clinical Procedure: Reimplantation
      of the left coronary artery to the aorta Specialty: Pediatrics and Neonatology.
      OBJECTIVE: Rare disease. BACKGROUND: Bland-White-Garland syndrome (BWGS) is a
      very rare disease characterized by anomalous origin of the left coronary artery
      from the pulmonary trunk (ALCAPA). WBGS affects 1 in every 300 000 live births.
      Children typically present with dyspnea, pallor, and failure to thrive. Without
      surgical repair, most of these children die during the first months of life. CASE
      REPORT: This case report describes 3-month-old boy admitted to the hospital
      because of feeding problems. The boy was born at term, with birth weight 3200 g,
      and was 10 points in Apgar score. He was breast-fed from birth. From the seventh
      week of age, his mother observed his increasing difficulties with feeding.
      Physical examination revealed pale skin, diminished heart sounds, tachycardia,
      cardiomegaly, and hepatomegaly. Results of urine and blood tests and
      ultrasonography of the central nervous system and abdomen were normal. The chest
      radiography showed cardiomegaly and electrocardiogram revealed anterolateral
      myocardial infarction. On echocardiography, an anomalous left coronary artery
      arising from the pulmonary artery was found. The life-saving treatment of choice
      was immediate surgical reimplantation of the left coronary artery to the aorta.
      CONCLUSIONS: Children with congenital heart disease are often prone to
      malnutrition, but in rare cases failure to thrive and breast-feeding problems can
      be the first symptoms of life-threatening diseases like myocardial infarction
      secondary to Bland-White-Garland syndrome (BWGS).

PMID- 24086794
TI  - High fluorodeoxyglucose ((18)F)PET-uptake lymph nodes in a patient with chordoma:
      Tumor metastasis or sarcoidosis?
AB  - PATIENT: Male, 48 FINAL DIAGNOSIS: Chordoma Symptoms: - MEDICATION: - Clinical
      Procedure: - Specialty: Neurology. OBJECTIVE: Challenging differential diagnosis.
      BACKGROUND: Fluorodeoxyglucose positron emission tomography (FDG-PET) has been
      used in imaging and staging of malignancies including sacral chordomas. CASE
      REPORT: The author's report describes the coincident pathological diagnosis of
      sarcoidosis in a 48-year-old male patient with a recurrent sacral chordoma.
      Chordoma is a low grade malignancy with frequent systemic metastases in advanced
      disease. Both metastases and sarcoidosis may be high FDG uptake. Unexpected PET
      findings need to be biopsied in order to make appropriate clinical decision in
      the management of chordoma. CONCLUSIONS: Lymph nodes involvement in sarcoidosis
      and neoplastic disease can have similar FDG-PET manifestations.

PMID- 24086795
TI  - Effects of self-assembled monolayer structural order, surface homogeneity and
      surface energy on pentacene morphology and thin film transistor device
      performance.
AB  - A systematic study of six phosphonic acid (PA) self-assembled monolayers (SAMs)
      with tailored molecular structures is performed to evaluate their effectiveness
      as dielectric modifying layers in organic field-effect transistors (OFETs) and
      determine the relationship between SAM structural order, surface homogeneity, and
      surface energy in dictating device performance. SAM structures and surface
      properties are examined by near edge X-ray absorption fine structure (NEXAFS)
      spectroscopy, contact angle goniometry, and atomic force microscopy (AFM). Top
      contact pentacene OFET devices are fabricated on SAM modified Si with a thermally
      grown oxide layer as a dielectric. For less ordered methyl- and phenyl-terminated
      alkyl ~(CH2)12 PA SAMs of varying surface energies, pentacene OFETs show high
      charge carrier mobilities up to 4.1 cm2 V-1 s-1. It is hypothesized that for
      these SAMs, mitigation of molecular scale roughness and subsequent control of
      surface homogeneity allow for large pentacene grain growth leading to high
      performance pentacene OFET devices. PA SAMs that contain bulky terminal groups or
      are highly crystalline in nature do not allow for a homogenous surface at a
      molecular level and result in charge carrier mobilities of 1.3 cm2 V-1 s-1 or
      less. For all molecules used in this study, no causal relationship between SAM
      surface energy and charge carrier mobility in pentacene FET devices is observed.

PMID- 24086796
TI  - Motion compensation using a suctioning stabilizer for intravital microscopy.
AB  - Motion artifacts continue to present a major challenge to single cell imaging in
      cardiothoracic organs such as the beating heart, blood vessels, or lung. In this
      study, we present a new water-immersion suctioning stabilizer that enables
      minimally invasive intravital fluorescence microscopy using water-based stick
      objectives. The stabilizer works by reducing major motion excursions and can be
      used in conjunction with both prospective or retrospective gating approaches. We
      show that the new approach offers cellular resolution in the beating murine heart
      without perturbing normal physiology. In addition, because this technique allows
      multiple areas to be easily probed, it offers the opportunity for wide area
      coverage at high resolution.

PMID- 24086797
TI  - The direction of development for archives of plastic surgery.

PMID- 24086798
TI  - Aging blepharoplasty.
AB  - In performing upper blepharoplasty in the elderly, looking younger and keeping
      the eyelids harmonious with the rest of the face have to be achieved at the same
      time. The most important goal in upper blepharoplasty for aging is correcting the
      drooping upper eyelid skin, and in this process, the surgeon may or may not
      create a double eyelid fold. The pros and cons have to be fully discussed with
      the patient, but the author personally prefers creating a double fold unless the
      patient refuses, because it is efficient in correcting and preventing further
      drooping of the skin. In most patients, the brow is elevated to compensate for
      the drooping eyelid, and when the drooping is corrected, brow ptosis may ensue.
      The surgeon has to prepare for these consequences before performing the
      procedure, and estimate the exact amount of skin to be excised. In the elderly,
      the skin and the orbicularis oculi muscle is thin, with a decreased amount of
      subcutaneous fat and retro-orbicularis oculi fat, and in most cases, excision of
      the skin alone is enough to correct the deformity. Removing large portions of
      soft tissue may also prolong the recovery period. Unlike younger patients, the
      lower skin flap should not be stretched too much in the elderly, as it may create
      an aggressive looking appearance. A few wrinkles in the lower flap should remain
      untouched to create a natural look. In this article, the author's own methods of
      performing an aging blepharoplasty are described specifically, with a step-by
      step guide and surgical tips. 

PMID- 24086799
TI  - Where is the Lesion? Glomus Tumours of the Hand.
AB  - Glomus tumours are vascular hamartomas that are commonly found in the hand,
      particularly the subungual region. They appear as solitary or multiple tumours,
      and often present as a bluish discoloration of the nail plate. Different
      diagnostic tests are outlined, as well as imaging studies such as magnetic
      resonance imaging and ultrasound. Misdiagnosis and delayed diagnosis of these
      tumours are common, while a familial tendency is a potential risk factor but not
      yet proven. Complete surgical excision often results in complete symptomatic
      relief, while recurrences are largely due to incomplete excision or the growth of
      a new glomus tumour. This article aims to review the key aspects of glomus
      tumours and provide a diagnostic algorithm so that the lesion can be recognized
      and treated earlier. 

PMID- 24086800
TI  - Effect of amniotic fluid stem cells and amniotic fluid cells on the wound healing
      process in a white rat model.
AB  - BACKGROUND: Amniotic-fluid-derived stem cells and amniocytes have recently been
      determined to have wound healing effects, but their mechanism is not yet clearly
      understood. In this study, the effects of amniotic fluid stem cells and
      amniocytes on wound healing were investigated through animal experiments.
      METHODS: On the back of Sprague-Dawley rats, four circular full-thickness skin
      wounds 2 cm in diameter were created. The wounds were classified into the
      following four types: a control group using Tegaderm disc wound dressings and
      experimental groups using collagen discs, amniotic fluid stem cell discs, and
      amniocyte discs. The wounds were assessed through macroscopic histological
      examination and immunohistochemistry over a period of time. RESULTS: The amniotic
      fluid stem cell and amniocyte groups showed higher wound healing rates compared
      with the control group; histologically, the inflammatory cell invasion
      disappeared more quickly in these groups, and there was more significant
      angiogenesis. In particular, these groups had significant promotion of epithelial
      cell reproduction, collagen fiber formation, and angiogenesis during the initial
      10 days of the wound healing process. The potency of transforming growth factor
      beta and fibronectin in the experimental group was much greater than that in the
      control group in the early stage of the wound healing process. In later stages,
      however, no significant difference was observed. CONCLUSIONS: The amniotic fluid
      stem cells and amniocytes were confirmed to have accelerated the inflammatory
      stage to contribute to an enhanced cure rate and shortened wound healing period.
      Therefore, they hold promise as wound treatment agents.

PMID- 24086801
TI  - The Relationship between Oxygen Saturation and Color Alteration of a Compromised
      Skin Flap: Experimental Study on the Rabbit.
AB  - BACKGROUND: The aim of this study was to collect important data on the time of
      oxygen saturation change in relation to skin flap color alteration using non
      invasive pulse oximetry to evaluate its ability to provide continuous monitoring
      of skin flap perfusion. METHODS: An experimental study on the monitoring of blood
      perfusion of 20 tube-island groin flaps of 10 male New Zealand rabbits was
      performed using pulse oximetry. The animals were randomly assigned to one of two
      groups representing a blockage of either arterial or venous blood flow. The
      oxygen saturation change and clinical color alteration were monitored from the
      beginning of vessel clamping until the saturation became undetectable. The result
      was analyzed by the t-test using SSPS ver. 10.0. RESULTS: The mean times from the
      vessel clamping until the saturation became undetectable were 20.19+/-2.13
      seconds and 74.91+/-10.57 seconds for the artery and vein clamping groups,
      respectively. The mean time of the clinical alteration from the beginning of vein
      clamping was 34.5+/-11.72 minutes, while the alteration in flaps with artery
      clamping could not be detected until 2.5 hours after clamping. CONCLUSIONS: The
      use of neonate-type reusable flex sensor-pulse oximetry is objective and
      effective in early detection of arterial and vein blockage. It provides real-time
      data on vessel occlusion, which in turn will allow for early salvaging. The
      detection periods of both arterial occlusion and venous congestion are much
      earlier than the color alteration one may encounter clinically.

PMID- 24086802
TI  - Proposed treatment protocol for frostbite: a retrospective analysis of 17 cases
      based on a 3-year single-institution experience.
AB  - BACKGROUND: This paper discusses the treatment protocol for patients with
      frostbite. METHODS: We performed a retrospective analysis of a series of 17
      patients with second- and higher-degree frostbite who had been treated at our
      medical institution between 2010 and 2012. RESULTS: Our clinical series of
      patients (n=17) included 13 men and four women, whose mean age was 42.4+/-11.6
      years (range, 22-67 years). The sites of injury include the foot in six patients
      (35.3%), the hand in six patients (35.3%) and the facial region in five patients
      (29.4%). Seven patients with second-degree frostbite were completely cured with
      only conservative treatment during a mean period of 12.7+/-3.3 days (range, 8-16
      days). Of the five patients with third-degree frostbite, two underwent skin
      grafting following debridement, and the remaining three achieved a complete cure
      with conservative treatment during a mean period of 35+/-4.3 days (range, 29-39
      days). Five patients with fourth-degree frostbite were treated with surgical
      procedures including amputation. CONCLUSIONS: With the appropriate conservative
      management in the early stage of onset, surgeons should decide on surgery after
      waiting for a sufficient period of time until the demarcation of the wound.
      Continuous management of patients is also needed to achieve functional recovery
      after a complete cure has been achieved. This should also be accompanied by
      patient education for the avoidance of re-exposure to cold environments.

PMID- 24086803
TI  - Expression of extracellular superoxide dismutase protein in diabetes.
AB  - BACKGROUND: Diabetes is characterized by chronic hyperglycemia, which can
      increase reactive oxygen species (ROS) production by the mitochondrial electron
      transport chain. The formation of ROS induces oxidative stress and activates
      oxidative damage-inducing genes in cells. No research has been published on
      oxidative damage-related extracellular superoxide dismutase (EC-SOD) protein
      levels in human diabetic skin. We investigated the expression of EC-SOD in
      diabetic skin compared with normal skin tissue in vivo. METHODS: The expression
      of EC-SOD protein was evaluated by western blotting in 6 diabetic skin tissue
      samples and 6 normal skin samples. Immunohistochemical staining was also carried
      out to confirm the EC-SOD expression level in the 6 diabetic skin tissue samples.
      RESULTS: The western blotting showed significantly lower EC-SOD protein
      expression in the diabetic skin tissue than in the normal tissue.
      Immunohistochemical examination of EC-SOD protein expression supported the
      western blotting analysis. CONCLUSIONS: Diabetic skin tissues express a
      relatively small amount of EC-SOD protein and may not be protected against
      oxidative stress. We believe that EC-SOD is related to the altered metabolic
      state in diabetic skin, which elevates ROS production.

PMID- 24086804
TI  - The Relationship between Preoperative Wound Classification and Postoperative
      Infection: A Multi-Institutional Analysis of 15,289 Patients.
AB  - BACKGROUND: Despite advances in surgical techniques, sterile protocols, and
      perioperative antibiotic regimens, surgical site infections (SSIs) remain a
      significant problem. We investigated the relationship between wound
      classification (i.e., clean, clean/contaminated, contaminated, dirty) and SSI
      rates in plastic surgery. METHODS: We performed a retrospective review of a multi
      institutional, surgical outcomes database for all patients undergoing plastic
      surgery procedures from 2006-2010. Patient demographics, wound classification,
      and 30-day outcomes were recorded and analyzed by multivariate logistic
      regression. RESULTS: A total of 15,289 plastic surgery cases were analyzed. The
      overall SSI rate was 3.00%, with superficial SSIs occurring at comparable rates
      across wound classes. There were similar rates of deep SSIs in the clean and
      clean/contaminated groups (0.64%), while rates reached over 2% in contaminated
      and dirty cases. Organ/space SSIs occurred in less than 1% of each wound
      classification. Contaminated and dirty cases were at an increased risk for deep
      SSIs (odds ratios, 2.81 and 2.74, respectively); however, wound classification
      did not appear to be a significant predictor of superficial or organ/space SSIs.
      Clean/contaminated, contaminated, and dirty cases were at increased risk for a
      postoperative complication, and contaminated and dirty cases also had higher odds
      of reoperation and 30-day mortality. CONCLUSIONS: Analyzing a multi-center
      database, we found that wound classification was a significant predictor of
      overall complications, reoperation, and mortality, but not an adequate predictor
      of surgical site infections. When comparing infections for a given wound
      classification, plastic surgery had lower overall rates than the surgical
      population at large.

PMID- 24086805
TI  - Platelet-rich plasma: quantitative assessment of growth factor levels and
      comparative analysis of activated and inactivated groups.
AB  - BACKGROUND: Platelet-rich plasma (PRP) has more concentrated platelets than
      normal plasma (approximately 150-400*10(3) cell/dL). Platelets excrete several
      growth factors and cytokines that are associated with the healing and
      regeneration process. However, even though PRP is widely used, the mechanism or
      actual effect is presently unclear. Therefore, this study was performed to
      investigate the levels of growth factors and platelet concentration rate.
      METHODS: Autologous blood for preparing PRP was obtained from healthy subjects
      aged 25 to 35 years. The samples were divided into 4 experimental groups
      (inactivated whole blood, inactivated PRP, activated whole blood with thrombin
      and calcium chloride, and activated PRP). The platelet counts in the blood were
      analyzed and the growth factors were quantitatively measured. A statistical
      analysis was performed by using Dunn's multiple comparison test. RESULTS: In the
      blood cell analysis, the platelet count of the PRP group was approximately 4.25
      times higher than that of the whole blood group. In the quantitative analysis of
      growth factors, the platelet-derived growth factor (PDGF)-AB, PDGF-BB, and
      transforming growth factor-beta of the inactivated and activated PRP groups were
      higher than those of the inactivated and activated whole blood groups (P<0.05).
      CONCLUSIONS: In this study, the platelet count and the levels of PDGF-AB and PDGF
      BB in the PRP were determined. Further, more research is required on the
      bioactivity level of the growth factors secreted during the process of PRP
      preparation and the potency of growth factors that can be exerted physiologically
      in vivo.

PMID- 24086806
TI  - Nasal carriage of 200 patients with nasal bone fracture in Korea.
AB  - BACKGROUND: Pathogens in the nasal cavity during nasal surgery could lead to a
      systemic infectious condition, such as bacteremia, nosocomial infection, or toxic
      shock syndrome. However, there is no research about the prevalence of nasal
      carriage in patients with nasal bone fracture. METHODS: This was a prospective,
      double-blind, randomized study about the rate of nasal carriage in 200 patients
      with nasal bone fracture in Korea. Nasal secretions were taken from both the
      middle nasal meatus and colonized. All analyses were carried out using SPSS
      software. RESULTS: Pathogens were identified in 178 of the 200 cases. Coagulase
      negative staphylococci (CNS) were the most cultured bacteria in 127 (66.84%) of
      the 190 total patients after excluding 10 cases of contaminated samples, and
      methicillin-resistant coagulase-negative staphylococci (MRCNS) were found in 48
      (25.26%). Staphylococcus aureus was the second most identified pathogen, found in
      36 (18.95%), followed by 7 cases (3.68%) of methicillin-resistant Staphylococcus
      aureus (MRSA). The prevalence rate of MRSA in the females was higher than that in
      the males (RR=4.70; 95% CI, 1.09-20.18), but other demographic factors had no
      effect on the prevalence rate of MRSA and MRCNS. CONCLUSIONS: The prevalence rate
      of these pathogens in patients with nasal bone fracture in Korea was similar to
      other reports. However, few studies have addressed the prevalence rate of CNS and
      MRCNS in accordance with risk factors or the change in prevalence according to
      specific prophylaxis against infectious complications. Additional research is
      needed on the potential connections between clinical factors and microbiological
      data.

PMID- 24086807
TI  - Nostril base augmentation effect of alveolar bone graft.
AB  - BACKGROUND: The aims of alveolar bone grafting are closure of the fistula,
      stabilization of the maxillary arch, support for the roots of the teeth adjacent
      to the cleft on each side. We observed nostril base augmentation in patients with
      alveolar clefts after alveolar bone grafting. The purpose of this study was to
      evaluate the nostril base augmentation effect of secondary alveolar bone grafting
      in patients with unilateral alveolar cleft. METHODS: Records of 15 children with
      alveolar clefts who underwent secondary alveolar bone grafting with autogenous
      iliac cancellous bone between March of 2011 and May of 2012 were reviewed.
      Preoperative and postoperative worm's-eye view photographs and reconstructed
      three-dimensional computed tomography (CT) scans were used for photogrammetry.
      The depression of the nostril base and thickness of the philtrum on the cleft
      side were measured in comparison to the normal side. The depression of the cleft
      side pyriform aperture was measured in comparison to the normal side on
      reconstructed three-dimensional CT. RESULTS: Significant changes were seen in the
      nostril base (P=0.005), the philtrum length (P=0.013), and the angle (P=0.006).
      The CT measurements showed significant changes in the pyriform aperture (P<0.001)
      and the angle (P<0.001). CONCLUSIONS: An alveolar bone graft not only fills the
      gap in the alveolar process but also augments the nostril base after surgery. In
      this study, only an alveolar bone graft was performed to prevent bias from other
      procedures. Nostril base augmentation can be achieved by performing alveolar bone
      grafts in children, in whom invasive methods are not advised.

PMID- 24086808
TI  - Clinical Follow-up on Sagittal Fracture at the Temporal Root of the Zygomatic
      Arch: Does It Need Open Reduction?
AB  - BACKGROUND: The zygoma is a major portion of the midfacial contour. When
      deformity occurs in this area, a reduction should be conducted to correct it. If
      a sagittal fracture at the temporal root of the zygomatic arch occurs, this also
      requires reduction, but it is difficult to approach due to its anatomical
      location, and the possibility of fixation is also limited. Thus, the authors
      attempted the reduction of sagittal fracture by two- or three-point fixation and
      the Gillies approach without direct manipulation. The preoperative and
      postoperative results of the patients were evaluated. Follow-up was performed to
      establish a treatment guideline. METHODS: A retrospective study was done with 40
      patients who had sagittal fractures at the temporal root of the zygomatic arch
      from March 2009 to June 2012. Only two- or three-point fixation was performed for
      the accompanying zygomatic-orbital-maxillary fracture. The Gillies approach was
      used for complex fractures of the zygomatic arch, while the temporal root of the
      zygomatic arch was only observed without reduction. Preoperative and
      postoperative computed tomography and X-ray scans were performed to examine the
      results. RESULTS: The result of the paired t-test on preoperative and
      postoperative bone gap differences, the depression level, and the degree of
      temporal protrusion showed a marked decrease in the mean difference at a 95%
      confidence interval. The results were acceptable. CONCLUSIONS: In the treatment
      of sagittal fractures at the temporal root of the zygomatic arch, it is
      acceptable to use indirect reduction and non-fixation methods. This leads to a
      satisfactory aesthetic and functional outcome.

PMID- 24086809
TI  - One-stage nipple and breast reconstruction following areola-sparing mastectomy.
AB  - BACKGROUND: Skin-sparing mastectomy with immediate breast reconstruction is
      increasingly becoming a proven surgical option for early-stage breast cancer
      patients. Areola-sparing mastectomy (ASM) has also recently become a popular
      procedure. The purpose of this article is to investigate the reconstructive and
      aesthetic issues experienced with one-stage nipple and breast reconstruction
      using ASM. METHODS: Among the patients who underwent mastectomy between March
      2008 and March 2010, 5 women with a low probability of nipple-areolar complex
      malignant involvement underwent ASM and immediate breast reconstruction with
      simultaneous nipple reconstruction using the modified C-V flap. The cosmetic
      outcomes of this series were reviewed by plastic surgeons and patient self
      assessment and satisfaction were assessed via telephone interview. RESULTS:
      During the average 11-month follow-up period, there were no cases of cancer
      recurrence, the aesthetic outcomes were graded as excellent to very good, and all
      of the patients were satisfied. Two patients developed a gutter-like depression
      around the reconstructed nipple, and one patient developed skin erosion in a
      small area of the areola, which healed with conservative dressing. The other
      complications, such as necrosis of the skin flap or areola, seroma, hematoma, or
      fat necrosis did not occur. CONCLUSIONS: Since one-stage nipple and breast
      reconstruction following ASM is an oncologically safe, cost-effective, and
      aesthetically satisfactory procedure, it is a good surgical option for early
      breast cancer patients.

PMID- 24086810
TI  - The effect of breast hypertrophy on patient posture.
AB  - BACKGROUND: One of the reasons women with macromastia chose to undergo a breast
      reduction is to relieve their complaints of back, neck, and shoulder pain. We
      hypothesized that changes in posture after surgery may be the reason for the pain
      relief and that patient posture may correlate with symptomatic macromastia and
      may serve as an objective measure for complaints. The purpose of our study was to
      evaluate the effect of reduction mammaplasty on the posture of women with
      macromastia. METHODS: A prospective controlled study at a university medical
      center. Forty-two patients that underwent breast reduction were studied before
      surgery and an average of 4.3 years following surgery. Thirty-seven healthy women
      served as controls. Standardized lateral photos were taken. The inclination angle
      of the back was measured. Regression analysis was performed for the inclination
      angle. RESULTS: Preoperatively, the mean inclination angle was 1.61 degrees
      ventrally; this diminished postoperatively to 0.72 degrees ventrally. This change
      was not significant (P-value=0.104). In the control group that angle was 0.28
      degrees dorsally. Univariate regression analysis revealed that the inclination
      was dependent on body mass index (BMI) and having symptomatic macromastia; on
      multiple regression it was only dependent on BMI. CONCLUSIONS: The inclination
      angle of the back in breast reduction candidates is significantly different from
      that of controls; however, this difference is small and probably does not account
      for the symptoms associated with macromastia. Back inclination should not be used
      as a surrogate "objective" measure for symptomatic macromastia.

PMID- 24086811
TI  - Application of local axial flaps to scalp reconstruction.
AB  - BACKGROUND: Scalp defects may be caused by various etiological factors, and they
      represent a significant surgical and aesthetic concern. Various surgical
      techniques can be applied for reconstructive work such as primary closure, skin
      grafting, pedicled or free flaps. In this article, the authors share their
      clinical experience with scalp operations using the technique of local flaps and
      discuss the application of this method from the perspective of not only the size
      of the defect, but also in relation to the anatomical area, quality of
      surrounding tissue, and patient's condition. METHODS: During the period from
      December 2007 to December 2012, 13 patients with various scalp defects, aged 11
      to 86 years, underwent reconstruction with local pedicle flaps. The indications
      were based on the patients' condition (age, sex, quality of surrounding tissue,
      and comorbidities) and wound parameters. Depending on the size of the defects,
      they were classified into three groups as follows: large, 20 to 50 cm(2); very
      large, 50 to 100 cm(2); extremely large, 100 cm(2). The location was defined as
      peripheral (frontal, temporal, occipital), central, or combined (more than one
      area). We performed reconstruction with 11 single transposition flaps and 1
      bipedicle with a skin graft on the donor area, and 2 advancement flaps in 1
      patient. RESULTS: In all of the patients, complete tissue coverage was achieved.
      The recovery was relatively quick, without hematoma, seroma, or infections. The
      flaps survived entirely. CONCLUSIONS: Local flaps are widely used in scalp
      reconstruction since they provide healthy, stable, hair-bearing tissue and
      require a short healing time for the patients.

PMID- 24086812
TI  - Multidirectional vector excision leads to better outcomes than traditional
      elliptical excision of facial congenital melanocytic nevus.
AB  - BACKGROUND: The elliptical excision is the standard method of removing benign
      skin lesions, such as congenital melanocytic nevi. This technique allows for
      primary closure, with little to no dog-ear deformity, but may sacrifice normal
      tissue adjacent to the lesion, resulting in scars which are unnecessarily long.
      This study was designed to compare the predicted results of elliptical excision
      with those resulting from our excision technique. METHODS: Eighty-two patients
      with congenital melanocytic nevus on the face were prospectively studied. Each
      lesion was examined and an optimal ellipse was designed and marked on the skin.
      After an incision on one side of the nevus margin, subcutaneous undermining was
      performed in the appropriate direction. The skin flap was pulled up and
      approximated along several vectors to minimize the occurrence of dog-ear
      deformity. RESULTS: Overall, the final wound length was 21.1% shorter than that
      achieved by elliptical excision. Only 8.5% of the patients required dog-ear
      repair. There was no significant distortion of critical facial structures. All of
      the scars were deemed aesthetically acceptable based on their Patient and
      Observer Scar Assessment Scale scores. CONCLUSIONS: When compared to elliptical
      excision, our technique appears to minimize dogear deformity and decrease the
      final wound length. This technique should be considered an alternative method for
      excision of facial nevi.

PMID- 24086813
TI  - Reconstruction of the lower extremity using free flaps.
AB  - BACKGROUND: The aim of lower-extremity reconstruction has focused on wound
      coverage and functional recovery. However, there are limitations in the use of a
      local flap in cases of extensive defects of the lower-extremities. Therefore,
      free flap is a useful option in lower-extremity reconstruction. METHODS: We
      performed a retrospective review of 49 patients (52 cases) who underwent lower
      extremity reconstruction at our institution during a 10-year period. In these
      patients, we evaluated causes and sites of defects, types of flaps, recipient
      vessels, types of anastomosis, survival rate, and complications. RESULTS: There
      were 42 men and 10 women with a mean age of 32.7 years (range, 3-72 years). The
      sites of defects included the dorsum of the foot (19), pretibial area (17), ankle
      (7), heel (5) and other sites (4). The types of free flap included latissimus
      dorsi muscle flap (10), scapular fascial flap (6), anterolateral thigh flap (6),
      and other flaps (30). There were four cases of vascular complications, out of
      which two flaps survived after intervention. The overall survival of the flaps
      was 96.2% (50/52). There were 19 cases of other complications at recipient sites
      such as partial graft loss (8), partial flap necrosis (6) and infection (5).
      However, these complications were not notable and were resolved with skin grafts.
      CONCLUSIONS: The free flap is an effective method of lower-extremity
      reconstruction. Good outcomes can be achieved with complete debridement and the
      selection of appropriate recipient vessels and flaps according to the recipient
      site.

PMID- 24086814
TI  - Vascularisation of urethral repairs with the gracilis muscle flap.
AB  - BACKGROUND: The ability to achieve a long-term, stricture-free urethral repair is
      one of the ongoing challenges of reconstructive urologic surgery. A successful
      initial repair is critical, as repeat procedures are difficult, owing to
      distortion, scarring, and short urethral stumps. METHODS: We describe a technique
      in which the gracilis muscle flap is laid on or wrapped around the urethral
      repair site to provide a well-vascularised soft tissue reinforcement for urethral
      repair. This technique promotes vascular induction, whereby a new blood supply is
      introduced to the repair site to improve the outcome of urethral repair or
      anastomotic urethroplasty. The surface contact between the muscle flap and the
      repair site is enhanced by the use of fibrin glue to improve adherence and
      promote inosculation and healing. We employed this technique in 4 patients with
      different urethral defects. RESULTS: After a follow-up period of 32 to 108
      months, all of the urethral repairs were successful without complications.
      CONCLUSIONS: Our results suggest that the use of a gracilis muscle flap to
      vascularise urethral repairs can improve the outcome of challenging urethral
      repairs.

PMID- 24086815
TI  - Cost-effectiveness analysis in comparing alginate silver dressing with silver
      zinc sulfadiazine cream in the treatment of pressure ulcers.
AB  - BACKGROUND: The treatment of pressure ulcers is complicated, given the various
      wound dressing products available. The cost of different treatments varies and
      the cost-effectiveness of each product has not been thoroughly evaluated. We
      compare two wound dressing protocols-alginate silver dressing (AlSD) and silver
      zinc sulfadiazine cream (AgZnSD) with regard to wound healing and cost
      effectiveness. METHODS: Patients with grade III or IV sacral or trochanteric
      pressure ulcers were eligible for this prospective, randomized controlled trial.
      The patients were randomized to receive one of the two dressings for an eight
      week period. The criteria of efficacy were based on the Pressure Ulcer Scale for
      Healing (PUSH) scoring tool. The cost of treatment was also assessed. RESULTS:
      Twenty patients (12 women and 8 men) were randomly assigned to receive either
      AlSD (n=10) or AgZnSD cream (n=10). The demographic data and wound
      characteristics were comparable in the two groups. The two groups showed no
      significant difference in the reduction of PUSH score, wound size, or volume of
      exudate. The tissue type score was significantly lower in the AlSD group (3.15+/
      0.68-1.85+/-0.68 vs. 2.73+/-0.79-2.2+/-0.41; P=0.015). The cost of treatment was
      significantly lower in the AlSD group (377.17 vs. 467.74 USD, respectively;
      P<0.0001). CONCLUSIONS: Alginate silver dressing could be effectively used in the
      treatment of grade III and IV pressure ulcers. It can improve wound tissue
      characteristics and is cost-effective.

PMID- 24086816
TI  - Forehead augmentation with a methyl methacrylate onlay implant using an injection
      molding technique.
AB  - BACKGROUND: The forehead, which occupies about one third of the face, is one of
      the major determinants of a feminine or masculine look. Various methods have been
      used for the augmentation of the forehead using autologous fat grafts or
      alloplastic materials. Methylmethacrylate (MMA) is the most appropriate material
      for augmentation of the forehead, and we have used an injection-molding technique
      with MMA to achieve satisfactory results. METHODS: Under local anesthesia with
      intravenous (IV) sedation, an incision was made on the scalp and a meticulous and
      delicate subperiosteal dissection was then performed. MMA monomers and polymers
      were mixed, the dough was injected into the space created, and manual molding was
      performed along with direct inspection. This surgery was indicated for patients
      who wanted to correct an unattractive appearance by forehead augmentation. Every
      patient in this study visited our clinics 3 months after surgery to evaluate the
      results. We judged the postoperative results in terms of re-operation rates
      caused by the dissatisfaction of the patients and complications. RESULTS: During
      a 13-year period, 516 patients underwent forehead augmentation with MMA. With the
      injection-molding technique, the inner surface of the MMA implant is positioned
      close to the underlying frontal bone, which minimizes the gap between the implant
      and bone. The borders of the implant should be tapered sufficiently until no
      longer palpable or visible. Only 28 patients (5.4%) underwent a re-operation due
      to an undesirable postoperative appearance. CONCLUSIONS: The injection-molding
      technique using MMA is a simple, safe, and ideal method for the augmentation of
      the forehead.

PMID- 24086817
TI  - Direct brow lift combined with suspension of the orbicularis oculi muscle.
AB  - BACKGROUND: Although the conventional direct brow lift operation provides a
      simple means of managing lateral brow ptosis, the scars produced have been
      unacceptable. However, using the modifications proposed here, scarring showed
      remarkable improvement. This article reviews our experiences with the presented
      technique, mainly with respect to postoperative scarring. METHODS: Measured
      amounts of supra-eyebrow skin and subcutaneous fat were excised en bloc in the
      conventional manner under 'hyper-hydrated' local infiltration anesthesia. The
      lower flap and the edge of the upper flap were undermined above the muscular
      plane, and the orbicularis oculi muscle was directly suture-plicated and
      suspended upward to the distal frontalis muscle. Skin closure was performed in a
      basic plastic surgical manner. RESULTS: From April 2007 to April 2012, a
      consecutive series of 60 patients underwent surgery using the above method. The
      average width of the excised skin was 8 mm (range, 5-15 mm) at the apex of the
      eyebrow. Preoperative complaints were resolved without occurrence of significant
      complications. The surgical scars showed remarkable improvement and were
      negligible in the majority of the cases. CONCLUSIONS: The direct brow lift
      operation combined with plication/suspension of the superior and lateral portion
      of the orbicularis oculi muscle provides a simple, safe, and predictable means of
      correcting lateral brow ptosis. The scars were acceptable to all of the patients.
      For proper management of the frontalis tone, upper blepharoplasty and/or repair
      of eyelid levator function must be considered in addition to brow lift
      procedures.

PMID- 24086818
TI  - Nasal anthropometry on facial computed tomography scans for rhinoplasty in
      koreans.
AB  - BACKGROUND: Cephalometric analysis is essential for planning treatment in
      maxillofacial and aesthetic facial surgery. Although photometric analysis of the
      Korean nose has been attempted in the past, anthropometry of the deeper nasal
      structures in the same population based on computerized tomography (CT) has not
      been published. We therefore measured three anthropometric parameters of the nose
      on CT scans in our clinical series of patients. METHODS: We conducted the current
      retrospective study of a total of 100 patients (n=100) who underwent a CT-guided
      radiological measurement at our institution during a period ranging from January
      of 2008 to August of 2010. In these patients, we took three anthropometric
      measurements: the nasofrontal angle, the pyramidal angle, and the linear distance
      between the nasion and the tip of the nasal bone. RESULTS: The mean nasofrontal
      angle was 131.14 degrees  in the male patients and 140.70 degrees  in the female
      patients. The mean linear distance between the nasion and the tip of the nasal
      bone was 21.28 mm and 18.02 mm, respectively. The mean nasal pyramidal angle was
      112.89 degrees  and 103.25 degrees  at the level of the nasal root, 117.49
      degrees  and 115.60 degrees  at the middle level of the nasal bone, and 127.99
      degrees  and 125.04 degrees  at the level of the tip of the nasal bone,
      respectively. CONCLUSIONS: In conclusion, our data will be helpful in the
      preparation of silicone implants for augmentation and/or corrective rhinoplasty
      in ethnic Korean people.

PMID- 24086819
TI  - L-shaped columellar strut in East asian nasal tip plasty.
AB  - BACKGROUND: Nasal tip support is an essential consideration for rhinoplasty in
      East Asians. There are many techniques to improve tip projection, and among them,
      the columellar strut is the most popular technique. However, the conventional
      design is less supportive for rotating the tip. The amount of harvestable septal
      cartilage is relatively small in East Asians. For an optimal outcome, we propose
      an L-shaped design for applying the columellar strut. METHODS: To evaluate the
      anthropometric outcomes, the change in nasal tip projection and the columella
      labial angle were analyzed by comparing preoperative and postoperative
      photographs. The anthropometric study group consisted of 25 patients who
      underwent the same operative technique of an L-shaped strut graft using septal
      cartilage and were followed up for more than 9 months. RESULTS: There were
      statistically significant differences between the preoperative and postoperative
      values in the nasal tip projection ratio and columella-labial angle. We did not
      observe any complications directly related to the L-shaped columellar strut in
      the anthropometric study group. CONCLUSIONS: The L-shaped columellar strut has
      advantages not only in the controlling of tip projection and rotation, but in
      that it needs a smaller amount of cartilage compared to the conventional septal
      extension graft. It can therefore be an alternative technique for nasal tip
      plasty when there is an insufficient amount of harvestable septal cartilage.

PMID- 24086821
TI  - Experience of ReCell in Skin Cancer Reconstruction.
AB  - The ReCell system (Avita Medical) is a cell culture product that allows the
      immediate processing of a small split-thickness skin biopsy to produce a complete
      population of cells including keratinocytes, melanocytes, Langerhans cells and
      fibroblasts. This series is the first to highlight the reconstructive
      applications of ReCell following ablative skin cancer surgery. The ReCell system
      was utilized for three patients following skin cancer excision. In two cases, the
      cells were applied to forehead flap donor sites following nasal reconstruction.
      In one case, the cells were applied to the calvarial periosteum following wide
      local excision of a melanoma scar. Assessment of the treated area was performed
      using the patient and observer scar assessment scale after 1 year. The Patient
      and Observer Scar Assessment Scale (POSAS) scores for the 2 patients treated with
      ReCell following forehead flap surgery were 22 and 32. The score for the patient
      that underwent wide local excision of a melanoma scar was 45. The absence of a
      donor site, accelerated healing and the satisfactory aesthetic appearance of the
      mature scars in this series suggest that ReCell may play a useful role in
      reconstruction following skin cancer excision. 

PMID- 24086820
TI  - Fibrin sealant and lipoabdominoplasty in obese grade 1 and 2 patients.
AB  - BACKGROUND: Ever since lipoabdominoplasty was first developed to achieve better
      aesthetic outcomes and less morbidity, the rate of seroma formation, especially
      in obese patients, has disturbed plastic surgeons. The aim of this study was to
      evaluate the effect of fibrin sealant in the prevention of seroma formation after
      lipoabdominoplasty in obese patients. METHODS: Sixty patients with a body mass
      index (BMI) between 30 and 39.9 were assigned randomly to 1 of 2 groups (30
      patients each). Group A underwent lipoabdominoplasty with fibrin glue, while
      group B underwent traditional lipoabdominoplasty; both had closed suction
      drainage applied to the abdomen. The patients' demographics and postoperative
      complications were recorded. Seroma was detected using abdominal ultrasound
      examinations at two postoperative periods: between postoperative days 10 and 12
      and, between postoperative days 18 and 21. RESULTS: The age range was 31 to 55
      years (38.5+/-9.5 years) in group A and 25 to 58 years (37.8+/-9.1 years) in
      group B, while the mean BMI was 31.4 to 39.9 kg/m(2) (32.6 kg/m(2)) in group A
      and 32.7 to 37.4 kg/m(2) (31.5 kg/m(2)) in group B. In group A, the patients had
      a complication rate of 10% in group A versus 43% in group B (P<0.05). The
      incidence of seroma formation was 3% in the fibrin glue group but 37% in the
      lipoabdominoplasty-alone group (P<0.05). CONCLUSIONS: Lipoabdominoplasty with the
      use of autologous fibrin sealant is a very effective method that significantly
      reduces the rate of postoperative seroma.

PMID- 24086822
TI  - Role of the surgical glove in modified vacuum-assisted wound healing.
AB  - Vacuum-assisted wound healing has been proven to be more efficacious than
      conventional dressings. Vacuum dressing has been frequently modified given the
      restrictions in resources available. Here we present a modified method of vacuum
      dressing by using surgical or gynaecological gloves for lower and upper limb
      wounds. Vacuum dressing was applied with parts of a surgical or gynaecological
      glove and Opsite with T-tailing of the suction outlet. Vacuum-assisted wound
      healing using the surgical gloves showed relatively good wound healing in the
      amputation stump, finger, arm, and leg in the cases studied. 

PMID- 24086824
TI  - Technical note on vacuum assisted closure-basket fixation of scrotal skin grafts.

PMID- 24086823
TI  - Smile restoration for permanent facial paralysis.

PMID- 24086825
TI  - Hidden sentinel node in cutaneous melanoma.

PMID- 24086826
TI  - Solitary labial metastasis of adrenocortical carcinoma resembling a cystic tumor
      in a child.

PMID- 24086827
TI  - Breast reconstruction in a previously explanted patient: an interesting
      anatomical anomaly.

PMID- 24086828
TI  - Penoscrotal Extramammary Paget's Disease with Multiple Lymph Node Metastasis.

PMID- 24086829
TI  - Use of a Silicone Gel Sheet Vaginal Mold in McIndoe Vaginoplasty.

PMID- 24086830
TI  - K-wire breakage during metalware removal due to a defective k-wire shaft.

PMID- 24086831
TI  - Korean society of plastic and reconstructive surgeons joint editorial symposium
      2013.

PMID- 24086832
TI  - Study of mastoid canals and grooves in north karnataka human skulls.
AB  - INTRODUCTION: This study was undertaken to observe the frequency of mastoid
      canals and grooves in north Karnataka dry human skulls. 100 dry human skulls of
      unknown age and sex from the department of Anatomy were selected and observed for
      the present study. MATERIAL AND METHODS: The mastoid regions of dry skulls were
      observed for the presence of mastoid canals and grooves, if any. A metallic wire
      was passed through the canal for its confirmation and then the length was
      measured. RESULTS: The Mastoid canals were present in 53% of the total 100 skulls
      observed either bilaterally or unilaterally. Mastoid grooves were present in 18%
      of the total skulls (100) observed. Double mastoid canal was found in 01% of
      total skull studied and both Mastoid canals & Mastoid grooves together were
      present in 02% of the total skulls (100) observed. CONCLUSION: The knowledge of
      mastoid canals and grooves is very important for otolaryngologists and
      neurosurgeons. Because they contain an arterial branch of occipital artery with
      its accompanying vein which is liable to injury resulting into severe bleeding.

PMID- 24086833
TI  - Facial indices of north and South Indian adults: reliability in stature
      estimation and sexual dimorphism.
AB  - INTRODUCTION: Anthropological studies have document differences in craniofacial
      features as well as in body characteristics among different populations. The
      variations in the facial morphology arise through a differential growth and they
      help us in distinguishing one person from another. These are controlled by a
      number of factors which include genetic heritage, climate and environment in
      which we live. Very few researchers from India have worked on these facial
      features with respect to population and environment. The present work was
      undertaken to determine whether facial variations were subjected to sexual
      dimorphism. In addition, comparison of facial indices was made, in order to
      determine possible variations between south and north Indian populations.
      METHODS: The sample consisted of 200 individuals, 100 each from north and south
      Indian regions. Various facial parameters were determined on the basis of
      international anatomical description and facial indices were calculated. RESULTS:
      North Indian males and females had highest facial height and upper facial height.
      Facial width of south Indians was more as compared to that of north Indians in
      both sexes. Regression equation was calculated to compare the probable height
      with actual height. CONCLUSION: All the facial parameters and facial indices were
      found to be statistically highly significant and they showed inter-regional and
      gender variations. These indices will be beneficial in facial reconstruction
      surgeries, maxillofacial surgeries, and in forensic medicine, for estimating the
      stature and sex of an individual.

PMID- 24086834
TI  - Evaluation of the variant anatomical disposition of the renal hilar structures in
      South Indian adult human cadavers and its cinical implications.
AB  - AIM: To evaluate the anatomical disposition of the renal hilar structures in
      human cadavers of south Indian origin, considering their antero-posterior
      distribution. MATERIAL AND METHODS: Ninty-six renal hila of the isolated kidneys
      from adult south Indian cadavers were observed for the branching patterns and the
      distributions of the renal hilar structures. The number of branches of the renal
      artery and the divisions of the renal vein in the pre hilar region were noted,
      along with their pattern of arrangement with respect to the renal pelvis.
      RESULTS: In the present study on the pre hilar region, we observed that the
      highest division of the renal artery was 8 and that the highest incidence was of
      4 divisions of the renal artery in 30.2% cases. The highest number of venous
      divisions which was observed was 7. The highest incidence of 40.6 % cases showed
      2 divisions of the veins. Regarding the patterns of arrangement of these
      structures, we observed 12 patterns of arrangement, with a higher incidence
      (45.8%) of the classical arrangement (V-A-P), as has been described in the
      standard text books of anatomy, which was followed by the A-V-P pattern (28.1%).
      CONCLUSION: An anatomical knowledge on the possible variant topography of the
      renal hilar structures is of great importance when urological surgical procedures
      are performed.

PMID- 24086835
TI  - The morphometric analysis of the mental foramen in adult dry human mandibles: a
      study on the South Indian population.
AB  - AIM: The mental foramen is a small foramen which is located in the antero-lateral
      aspect of the body of the mandible. It is situated midway between the upper and
      the lower border of the mandible and it transmits the mental nerve and the
      vessels. The knowledge on the anatomy of the mental foramen is very important in
      clinical dentistry and in surgical procedures which involve that area. MATERIAL
      AND METHODS: Our study was conducted on 90 adult dry human mandibles from the
      south Indian population, irrespective of age and sex. The location, shape,
      orientation and the presence of the accessory foramen were studied by visual
      examination. The size and position of the mental foramen were measured by using a
      digital vernier caliper. The SPSS, version 15 software was used for the
      statistical analysis, to calculate the minimum, maximum, incidence, mean and
      standard deviation. RESULTS: In a majority of the mandibles, the mental foramen
      was located at the level of the root of the 2(nd) premolar, midway between the
      inferior margin and the alveolar margin of the mandible. Most of the mental
      foramina were oval in shape. The orientation of the foramen was postero-superior
      in 83% of the mandibles. The accessory foramens were noted in five mandibles.
      CONCLUSION: The knowledge on the variations in the position and size of the
      mental foramen and the presence of the accessory foramen may be of much use to
      dental surgeons.

PMID- 24086836
TI  - Histopathological changes in the liver of rabbits exposed to high nitrate
      ingestion in drinking water.
AB  - OBJECTIVES: In India, especially in Rajasthan, people drink water which contains
      high level of nitrates and the possibility of finding concentrations of up to 500
      mg of nitrate ions per litre of water is not unusual. Excessive use of nitrate
      fertilisers and herbicides results in accumulation of nitrate in plants and
      methemoglobinaemia in cattle as consequences of nitrate poisoning. The ingested
      nitrate is converted to nitrite in the digestive system and it is absorbed in
      blood, thus causing methemoglobinaemia. Methaemoglobinaemia is not restricted to
      infants alone, but it is prevalent in higher age groups also. METHODS: Therefore,
      an experimental study was conducted on 10 rabbits which were between three and a
      half months to four months of age, which had weights which ranged from 1.310 kg
      to 1.720 kg. Five groups A, B, C,D and E were formed, with two rabbits in each
      group. The control Group A was given water orally, which had 45 mg/litres of
      nitrate. Groups B to E (experimental groups) were administered water orally,
      which had concentrations of 100mg/litre, 200mg/litre, 400mg/litre and 500mg/litre
      of nitrate respectively, for 120 days. During experimental period, the
      differences in general behaviour of rabbits were noted. After this, rabbits were
      anaesthetised and sacrificed according to guidelines of ICMR and their livers
      were removed and processed for making paraffin sections,.Hematoxyllin and eosin
      staining was done for microscopic observations. RESULTS: During experimental
      period, the animals were found to be lethargic on 75(th) day. Quantity of intake
      of food and water was not altered in the rabbits which were undergoing
      experiments in different groups. Rabbits of all groups i.e. A to E showed a
      continuous increase in heart rate (up to 218/minute in Group E) and respiration
      rate (up to 84/minute in Group E) respectively. The microscopic study showed mild
      necrosis of hepatocytes, with infiltration of inflammatory cells in between
      hepatocytes. In higher groups, the liver showed bridging necrosis and portal
      triditis. Dilatations of central vein with eosinophilic degeneration were
      observed in Group E only.

PMID- 24086837
TI  - Anatomical study of variations in the blood supply of kidneys.
AB  - BACKGROUND: Each kidney is supplied by a single renal artery and a single renal
      vein, which accounts for about 20% of the cardiac output. However, variations in
      the form of level of origin and arrangement of renal arteries are so frequent.
      AIM: The present study aimed to note the vascular anatomy of kidneys with respect
      to the variations in their origin, course and any aberrant vessels which were
      present. MATERIALS AND METHODS: The study material comprised of 15 formalin fixed
      human cadavers. During routine abdominal dissection for undergraduate students,
      the kidneys were exposed and the blood supply, along with its variations, were
      noted. RESULTS: The following anatomical findings are observed in this study: (i)
      Accessory renal arteries (ii) Presegmental arteries (iii) Upper polar arteries
      (iv) Lower polar arteries (v) Inferior suprarenal artery from accessory renal
      artery and (vi) Accessory renal vein. CONCLUSION: Awareness of the normal as well
      variational anatomy is mandatory for the surgeons, radiologists and urologists,
      for doing any uroradiological procedures or angiographic studies. Hence, this
      study will serve a useful guideline for the above mentioned procedures.

PMID- 24086838
TI  - Morphological study of lumbricals - a cadaveric study.
AB  - The apparently simple human function of closing the hand to grasp an object or
      opening the palm to release it are in reality tasks of considerable mechanical
      complexity requiring the contraction of many individual muscles Lumbricals are
      important part of intrinsic musculature of hand. Though several deviations from
      normal have been described in standard textbooks of anatomy, a review of basic
      anatomy of lumbricals will be helpful. AIM: Proper knowledge about anatomy and
      variaitions prevalent in intrinsic musculature of hand is mandatory for various
      surgical procedure like cleft hand surgery, pollicization & other digital
      transposition procedures Present study was conducted to study morphology &
      variations prevalent in this region. The results were compiled and tried to find
      out commonest variations Phylogenetical & ontogenetical basis and clinical
      applications related to variations encountered were tried to know by correlating
      it with available literature. MATERIAL & METHODS: For this study 50 hands of
      formalin embalmed cadavers were dissected The limbs were labelled R OR L for
      right or left, M or F for male or female. Cunnigham's manual for dissection was
      followed for dissection. RESULTS: Origin and nerve supply of lumbricals was
      normal in all hands. The variations were encountered in insertion of the 3rd
      lumbrical (32%) and 4th lumbrical (24%) were more confined to the right hand.
      Variations encountered commonly were split and misplaced insertion of third &
      fourth lumbricals. These variations are critically analyzed in the light of
      accessible literature. CONCLUSION: Lumbricals are more variable in the insertion
      rather than the origin & nerve supply. The variation commonly seen were split &
      misplaced insertion Split insertion was common in the third lumbrical whereas
      misplaced insertion is more common in the fourth lumbrical Variations are more
      common on right hands.

PMID- 24086839
TI  - Histomorphometric study of fructus psoralea on ethanol induced neurodegeneration
      of hippocampus in rat.
AB  - AIM: The histomophometric study of Fructus Psoralea (FP) on ethanol induced
      neurodegeneration of hippocampus was investigated in a rat by using micrometry.
      MATERIAL AND METHODS: The study was conducted on thirty healthy female adult
      wistar albino rats with regular 4-day estrus cycles. The experiment was carried
      out for a period of 2-4 months. The rats were divided into- SHAM operated control
      group (Group I) and experimental groups - overiectomised vehicle control rat
      ((Group II), OVX and orally treated with FP(Group III) OVX and induced with
      ethanol (Group IV), OVX rats induced with ethnaol and orally treated with FP
      (Group V). ANOVA tool was used to test the mean positive behavioural activity of
      all the groups. The diameter, packing density and the total number of neurons
      were calculated from toluidine blue stained histological section by using
      micrometry. The statistical package SPSS (17.0 VERSION) was used. Statistical
      significance was defined as p < 0.05. Data was expressed as mean +/- SEM.
      DISCUSSION: In animal studies, ethanol was found to significantly inhibit
      neuronal activity in the CA1 and CA3 pyramidal cell layers of the hippocampus. FP
      increase the number of cholinergic neurons in the basal forebrain which in turn
      leads to increased function of hippocampus, a structure heavily implicated in
      behavioural activity and memory consolidation. CONCLUSION: People with extensive
      hippocampal damage may experience amnesia, learning and memory disabilities.
      Hence the herb FP may be used as an adjuvant to treat the above neurological
      disorders.

PMID- 24086840
TI  - Correlation of the Osteogenic Protein-1 (OP-1) with Age, Cartilage metabolic
      Markers and Antioxidants in the Osteoarthritic Patients of Sikkim.
AB  - BACKGROUND: Age and oxidative stress have been implicated as the main causes of
      the cartilage damage in osteoarthritis (OA). The osteogenic protein-1(OP-1), a
      member of the bone morphogenetic family (BMP), plays a major role in cartilage
      repair. AIM: To correlate the OP-1 in the synovial fluid with the age and
      antioxidants like superoxide dismutase (SOD), glutathione peroxidase (GPx) and
      uric acid (UA) in the blood and with the cartilage metabolic markers like
      hyaluronic acid (HA) and keratan sulphate (KS) in the synovial fluid of
      osteoarthritic patients. METHOD: Seventy five osteoarthritic patients were taken
      up for the study. Heparinized blood samples were collected for the estimation of
      SOD, GPx and UA. Synovial fluid was aspirated for the estimation of HA, KS and OP
      1. OP-1 was estimated by using a polyclonal antibody (anti-OP-1) which was
      produced against OP-1 in the mouse ascitic fluid by sandwich ELISA. RESULT: Age
      and UA showed a significant correlation with OP-1. On the other hand, the
      correlations between OP-1 and the antioxidants (SOD and GPx) and the cartilage
      metabolic markers (HA and KS) were insignificant in osteoarthritic patients.
      CONCLUSION: The study suggests about the important role of OP-1 in cartilage
      aging and degeneration, which may help us in understanding the potential for the
      therapeutic interventions in the treatment of cartilage degenerative processes.

PMID- 24086841
TI  - Evaluation of the oxidative stress in chronic alcoholics.
AB  - AIM: The present study was conducted to assess the activity of Gamma Glutamyl
      Transferase (GGT) and its association with oxidative stress in alcoholics.
      METHOD: Sixty male alcoholics with a history of alcohol abuse for more than five
      years were the subjects of this study. Twenty healthy male volunteers who matched
      in age and the socio-economic status, served as the control subjects. RESULTS:
      GGT, reduced glutathione (GSH, a key intra-cellular antioxidant) and
      malondialdehyde (MDA, a marker of the oxidative stress) were assayed in the
      plasma of the two groups, and the results were statistically analyzed. The
      activity of the plasma GGT, known as a marker of Alcoholic Liver Disease (ALD);
      was significantly higher in the alcoholics as compared to that in the healthy
      controls. CONCLUSION: There was a significant positive correlation between the
      enzyme activity and the plasma levels of MDA and this indicated that there was an
      increased release of this enzyme with enhanced oxidative damage, due to the
      generation of oxygen free radicals in the study group. There was a significantly
      increased level of MDA and a decrease in the level of GSH in the alcoholics as
      compared to those in the controls. Significant negative correlations between GGT
      and GSH, and between MDA and GSH were observed. The present study demonstrates
      that alcoholics have a compromised antioxidant defense system.

PMID- 24086842
TI  - The micronutrient levels in the third trimester of pregnancy and assessment of
      the neonatal outcome: a pilot study.
AB  - CONTEXT: During pregnancy, an adequate intake of vitamins and minerals is
      recommended, to prevent the occurrence of adverse effects in the mother and the
      foetus. AIM: In our study, we aimed to study the levels of the micronutrients
      like iron, zinc and copper in the third trimester of pregnancy and to assess the
      neonatal outcome in them. MATERIAL AND METHODS: Fifty pregnant women who were
      aged 20-30 years, who had completed 24 weeks of gestation, who were on regular
      antenatal checkups, were included. The collected venous blood samples were used
      for the estimation of haemoglobin, serum ferritin, zinc and copper. They were
      followed up till their deliveries and the neonatal outcomes were noted. The
      gestational ages, weight of the babies, the lengths of the babies and their head
      circumferences and any complications which had occurred during and after the
      deliveries, were noted in the proforma. RESULTS: The serum ferritin levels did
      not significantly correlate with the other study parameters. The zinc levels
      decreased with an increase in the parity (p<0.05). The copper levels decreased
      with an increase in the BMI (p<0.05). With an increase in haemoglobin, there was
      an increase in the levels of zinc and ferritin (p<0.05). With an increase in the
      parity, there was a decrease in the neonatal birth weight. CONCLUSION: Our study
      clearly brought out a correlation between the microminerals such as iron, zinc
      and copper during late pregnancies. An improvement in the iron status brings out
      a positive effect on the ferritin and zinc levels, thus indicating better
      outcomes of the pregnancies.

PMID- 24086843
TI  - Case based learning: a method for better understanding of biochemistry in medical
      students.
AB  - INTRODUCTION: Health professionals need to develop analytic and diagnostic
      thinking skills and not just a mere accumulation of large amount of facts. Hence,
      Case Based Learning (CBL) has been used in the medical curriculum for this
      reason, so that the students are exposed to the real medical problems, which
      helps them in develop analysing abilities. This also helps them in interpreting
      and solving the problems and in the course of doing this, they develop interest.
      In addition to didactic lectures, CBL was used as a learning method. METHODS:
      This study was conducted in the Department of Biochemistry, S.B.K.S.M.I and R.C,
      Sumandeep Vidyapeeth ,Piparia, Gujarat, India. A group of 100 students were
      selected and they were divided into two groups as the control group and the study
      group. A total of 50 students were introduced to case based learning, which
      formed the study group and 50 students who attended didactic lectures formed the
      control group. RESULTS: A very significant improvement (p<0.0001) was observed
      among the students after the CBL sessions and they were also motivated by these
      sessions. A 4 point Likert scale questionnaire which contained 8 questions was
      administered to the students, to know their perception on the usefulness of the
      CBL. 98% of the students reported that they found the CBL sessions to be an
      interesting method of gaining knowledge. 84% of them felt that they exposed them
      to an experience of logical application of the knowledge which was gained in
      cracking cases, which would be of great help in the future also. CONCLUSION: Case
      Based Learning (CBL) was used and it is effective in the medical curriculum for a
      better understanding of Biochemistry among the medical students.

PMID- 24086844
TI  - Evaluation of Body Mass Index (BMI) Percentile cut-off Levels with Reference to
      Insulin Resistance: A Comparative Study on South Indian Obese and Non-Obese
      Adolescents.
AB  - OBJECTIVES: To investigate the relationship of Body Mass Index (BMI) percentile
      cut off with Homeostasis Model Assessment-Insulin Resistance (HOMA-IR), a
      surrogate marker for insulin resistance in obese, overweight and non-obese
      adolescents. STUDY DESIGN: A cross-sectional analysis of 120 adolescents (divided
      into sixty overweight/obese and an equal number of non-obese) was performed on
      nondiabetic, nonpregnant (11 to 18 year old school going) adolescents in south
      Indian (Puducherry) population. The main outcome measure of insulin resistance
      was calculated as HOMA-IR (greater than 3.16). Obesity was defined as per the BMI
      criteria, BMI greater than or equal to 95(th) percentile,overweight greater than
      or equal to 85(th) percentile and non-obese less than 84.9(th) percentile. All
      adolescents were subjected to analysis of anthropometric parameters that included
      weight, height and BMI (body mass index). Biochemical parameters, namely venous
      plasma glucose (fasting) and venous plasma insulin (fasting) were included for
      insulin resistance calculation by HOMA-IR. RESULTS: Having a BMI of greater than
      or equal to 85(th) percentilewas associated with high HOMA-IR levels. As the BMI
      percentile increased, HOMA-IR levels also increased. Prevalence of insulin
      resistance for a BMI percentile of less than 84.9 was nil. Prevalence of insulin
      resistance for a BMI percentile of 85-94.9 was 26%.Prevalence of insulin
      resistance for BMI of greater than or equal to 95(th) percentile was 64%.
      CONCLUSION: Insulin resistance is highly prevalent in obese and overweight
      adolescents as compared to that in non-obese adolescents. The onset of Impaired
      Fasting Glucose (IFG) is associated with the development of severe hyper
      insulinaemia in obese adolescents and early primordial and primary prevention can
      thus alleviate the burden of future cardiometabolic disorders.

PMID- 24086845
TI  - Thyroid function in type 2 diabetes mellitus and in diabetic nephropathy.
AB  - INTRODUCTION: Diabetic patients have higher prevalence of thyroid disorders than
      the general population which may have an influence on diabetic management. The
      present study compared the levels of thyroid hormones, serum creatinine, glycated
      haemoglobin and urine microalbumin between type 2 diabetics without any
      complications, type 2 diabetics with nephropathy and age and sex matched normal
      controls. RESULT: The mean serum T3 level in type 2 diabetics without any
      complications was 91.27 +/- 14.56 ng/dl , in type 2 diabetics with nephropathy
      was 88.5320 +/- 30.87 ng/dl and in controls was 134.98 +/- 28.55 ng/dl. The mean
      serum T4 level in type 2 diabetics without any complications was 7.73 +/- 1.42
      MUg/dl, in type 2 diabetics with nephropathy was 7.25 +/- 2.72 MUg/dl and in
      controls was 8.61 +/- 1.73 MUg/dl. The mean serum TSH level in type 2 diabetics
      without any complications was 3.99 +/- 1.87 MUIU/ml, in type 2 diabetics with
      nephropathy was 4.27 +/- 1.62 MUIU/ml and in controls was 2.07 +/- 1.09 MUIU/ml.
      Correlations between T3, T4, TSH with serum creatinine, glycated haemoglobin were
      not statistically significant in type 2 diabetes without any complications and
      diabetic nephropathy. We found a statistically significant correlation between T3
      and urine microalbumin in patients with diabetic nephropathy. CONCLUSION: Failure
      to recognize the presence of abnormal thyroid hormone levels may be a primary
      cause of poor management of diabetes mellitus type 2. Therefore there is a need
      for the routine assay of thyroid hormones in type 2 diabetics and diabetic
      nephropathy in order to improve the quality of life and reduce the morbidity.

PMID- 24086846
TI  - CSF Proteins as Discreminatory Markers of Tubercular and Pyogenic Meningitis.
AB  - INTRODUCTION: Meningitis is still a major cause of illness in many parts of the
      world. Though substantial improvement has been occurred in the diagnosis of
      meningitis, conclusive differentiation between tubercular and pyogenic meningitis
      remains to be an unsolved problem. Patients with meningitis often have severe
      neurological deficit or die inspite of antibiotic therapy. Thus, improvement in
      diagnostic test and therapy is required. The objective of the present study was
      to find a simple biochemical marker for diagnosis of meningitis and
      differentiation of tubercular and pyogenic meningitis. MATERIALS AND METHODS: CSF
      samples were collected from 90 paediatric patients from Nilofer Hospital,
      Hyderabad, India, from age group of 4 months to 12 years. CSF samples were
      collected by performing Lumbar Puncture under aseptic conditions and with
      required precaution. CSF samples were divided into 3 groups where Group 1
      included Control that was without CSF inflammation, Group 2 with Tuberculous
      Meningitis & Group 3 consisting of Pyogenic Meningitis with 30 samples in each
      group. Electrophoretic analysis of CSF proteins was performed which separated as
      bands of pre-albumin, albumin, alpha, beta and gamma globulins. RESULT: Protein
      content in CSF was 259 +/- 409 mg/dl in tuberculous meningitis, whereas in
      pyogenic meningitis it was 111 +/- 83.94 mg/dl and in control group was 19 +/-
      13.3 mg/dl. Electrophoretic analysis revealed pre-albumin band to be 2.8 +/- 1.2
      % in tuberculous meningitis, which was significantly decreased when compared with
      control and pyogenic meningitis. Albumin band in tuberculous meningitis was 34.8
      +/- 9.9 %, which was also significantly decreased when compared to control and
      pyogenic meningitis. Alpha band was 19.7 +/- 6.9 % in pyogenic meningitis, but in
      control and tubeculous meningitis it was 10.4 +/- 2.9% and 10.3 +/- 5.2%
      respectively. Beta band was found similar in all the three groups. Gamma band was
      33.2 +/- 8.08% in tuberculous meningitis, 13.8 +/- 4.55% in control and 16.7 +/-
      13.18% in pyogenic meningitis. CONCLUSION: Pre-albumin band was found to be
      decreased and gamma band was shown to be increased in tuberculous meningitis.
      Alpha band was increased in pyogenic meningitis. Thus, CSF protein fraction
      separated and quantitated by native Polyacrylamide slab gel electrophoresis,
      could be used as markers in differentiation of tubercular and pyogenic
      meningitis.

PMID- 24086847
TI  - Effect of wood dust on respiratory health status of carpenters.
AB  - INTRODUCTION: Occupational lung diseases form an important part of clinical
      medicine. Exposure to various chemicals or toxins which are manufactured or
      processed in industries are lethal for the workers in industries. Although these
      chemicals at workplace are known to invariably affect all body systems, lungs are
      most vulnerable to airborne hazards which are caused due to exposure to wood dust
      in welding, cement and wood industrial sectors. AIM AND OBJECTIVES: The aim of
      the present study was to establish the effect of wood dust on respiratory health
      of carpenters and to compare the measured values with those of age-matched
      controls. MATERIAL AND METHODS: This study involved 150 non-smoking carpenters,
      while 150 age-matched healthy non-smoking persons who were engaged in works other
      than carpentry, served as controls. The influence of age, height, body surface
      area (BSA) andduration of exposure on peak expiratory flow rate (PEFR) were
      determined in both cases and control subjects by using a Mini Wright's peak flow
      meter. The statistical analysis was done by using paired Student's t-test. A p
      value of < 0.05 was considered as statistically significant. RESULTS: The mean
      PEFR of study subjects was less than that of the control subjects in each sub
      group of age, height, weight and BSA and these results were statistically highly
      significant. CONCLUSION: The decrease in PEFR in carpenters was probably due to a
      continuous exposure to wood dust, which had caused an adverse effect on their
      respiratory status. In order to prevent the ill effects of wood dust on the
      respiratory health of carpenters, we suggest pre-employment medical check-ups and
      regular monitoring thereafter. Also, provision for a good ventilation at work
      place should be made.

PMID- 24086848
TI  - Evaluation of Salivary Profile among Adult Type 2 Diabetes Mellitus Patients in
      South India.
AB  - BACKGROUND: A lack of consensus on the possible association between diabetes and
      salivary dysfunction motivated us to conduct this investigation on the salivary
      parameters in diabetic and non diabetic subjects. This could also make the use of
      saliva as an alternative to that of blood in the diagnosis/monitoring of diabetes
      mellitus. OBJECTIVES: To compare the salivary flow rates and the salivary
      physical and biochemical parameters of diabetic (D) and non diabetic (ND)
      subjects. MATERIAL AND METHODS: The participants in this study included 30 non
      diabetic subjects and 30 diabetic volunteers who had Type 2 Diabetes mellitus for
      a minimum of 2 years. Unstimulated whole saliva was collected in the fasting
      state. Salivary pH, flow rate and organic and inorganic constituents were
      evaluated. Data which was collected was statistically analysed and interpreted.
      RESULTS: Salivary pH (ND=7.09+/-0.29, D=6.69+/-0.35), flow rate (ND=0.67+/-0.07,
      D=0.46+/-0.02) and salivary amylase (ND=92.51+/-13.74, D=19.20+/-1.8) were
      significantly lower in diabetics. They had significantly higher levels of
      salivary glucose (ND=4.33 +/- 0.29, D=17.31+/-2.05), total proteins (ND=424.46+/
      237.34, D=877.29+/-603.84), sodium (ND=4.31+/-0.65, D=14.42+/-1.83) and potassium
      (ND=20.84+/-0.71, D=25.95+/-1.56) and lower levels of calcium (ND=6.39+/-0.5,
      D=4.22+/-0.12) in comparison to those in the non-diabetic group. CONCLUSION:
      Significant variations were observed in salivary physical and biochemical
      parameters between diabetics and non diabetics. Evaluation of salivary parameters
      can be a cost effective and a non invasive alternative for screening, diagnosis
      and monitoring of diabetes, to blood.

PMID- 24086849
TI  - A comparative study of lipid profile and oestradiol in pre- and post-menopausal
      women.
AB  - OBJECTIVES: To investigate the relationship between the menopausal status and
      related hormonal variation of oestradiol with plasma lipid concentrations.
      MATERIAL AND METHODS: Fifty premenopausal women and fifty postmenopausal women
      subjects were selected. Data was collected through clinical evaluation from
      questionnaires and laboratory investigations. Plasma oestradiol and lipid profile
      determinations were done by using competitive binding immunoassay methods and
      enzymatic methods respectively. Student's T test and Pearson's test of
      correlation were used for the statistical analysis. P-values of < 0.05 were
      considered to be statistically significant. RESULTS: There was a significant
      increase in serum Total Cholesterol (TC), Triglycerides (TG), LDL-cholesterol and
      VLDL-cholesterol levels in post-menopausal women. HDL-cholesterol level was
      significantly decreased in post-menopausal women. The calculated atherogenic
      index (Total Cholesterol/HDL ratio) was significantly increased in post
      menopausal women as compared to that in premenopausal women. Oestradiol
      concentration was significantly lower (p<0.001) in post-menopausal women.
      DISCUSSION: Oestrogen changes the vascular permeability by increasing nitrous
      oxide production. It maintains a healthy lipoprotein profile. It stabilizes the
      endothelial cells, enhances antioxidant effect and alters fibrinolysis protein.
      All these cardioprotective mechanisms are lost in menopause. Postmenopausal women
      develop an increased risk for cardiovascular disease. CONCLUSION: Menopause leads
      to changes in lipid profile by reducing HDL, and elevating Total Cholesterol
      (TC), triglycerides (TG), LDL-cholesterol and VLDL-cholesterol, thus increasing
      the risk for cardiovascular disease. These changes are caused by reduced
      oestrogen concentrations which are seen in menopause.

PMID- 24086850
TI  - Asymptomatic obese hypertensives and need of routine echocardiography for left
      ventricular mass assessment and treatment.
AB  - BACKGROUND: Echocardiographic determination of Left Ventricle Mass (LVM) - an
      important marker of cardiovascular disease, has been given a lot of importance in
      clinical diagnosis and in planning of treatment. Clinically asymptomatic
      compensated hypertensives show some pathological findings which are indicative of
      left ventricular dysfunction. METHODS: The study population of 106 males, after a
      detailed clinical examination, were evaluated by echocardiography and were
      classified as per the body mass index classification of WHO Western Pacific
      Region in 2000 for Asian population. Fasting blood samples were taken to estimate
      blood sugar and lipid profile. RESULTS: It was observed that subjects in normal
      range of body mass index <45 years (23.68%) and >45 years (16.1%), subjects of
      overweight <45 years (15.7%) and >45 years (10.29%) and obese I and II<45 years
      (60.52%) and >45 years (73.52%). The comparison between left ventricular mass
      which was indexed to height(2.7) in subjects who were <45 years and >45years was
      observed to be statistically significant (p<0.03). On comparing LVM/ht(2.7) of
      normal BMI group with that of those with higher BMIs, it was noted to be
      significantly different (p<0.009), which was suggestive of adverse effects of
      increasing BMI on LVM. It was also observed that persons with increased BMIs
      showed changes in left ventricular geometry - 30.13% had concentric hypertrophy,
      17.80% had concentric remodeling, 8.21% had eccentric hypertrophy and that 38.35%
      had normal left ventricle geometry. CONCLUSION: The present study therefore,
      indicated that it was better to do an echocardiographic screening of asymptomatic
      subjects who had even a marginal increase in blood pressure and BMI, to diagnose
      potential cardiac dysfunction.

PMID- 24086851
TI  - Variation of reaction time in different phases of menstrual cycle.
AB  - OBJECTIVE: To evaluate the influence of menstrual cycle on auditory and visual
      reaction times. METHOD: This study was conducted on thirty, healthy, regularly
      menstruating female subjects who were in the age group of 18-25 years. Influence
      of different phases of menstrual cycle on Auditory Reaction Time (ART) and Visual
      Reaction Time (VRT) was evaluated by using a portable audiovisual reaction time
      apparatus. RESULT: The statistical tests which were used were ANOVA and Students
      't' test, which showed that there were significant increases in ART and VRT
      during luteal phase, as compared to those in follicular phase. CONCLUSION:
      Changes in ART and VRT during different phases of menstrual cycle could be due to
      changes in the levels of female sex hormones, which in turn may lead to salt and
      water retention.

PMID- 24086852
TI  - Pulmonary function tests in type 2 diabetics and non-diabetic people -a
      comparative study.
AB  - BACKGROUND: The complications which are associated with type 2 Diabetes mellitus
      are mostly caused by macro vascular and micro vascular damages. The pulmonary
      complications of diabetes mellitus have been poorly characterised. The present
      study has focused on the mechanical aspects of lung dysfunction which are
      attributable to type 2 Diabetes Mellitus; maximal forced Spiro metric Pulmonary
      Function Tests (PFTs) like Forced vital capacity (FVC), Forced Expiratory Volume
      in 1sec (FEV1),. FEV1/FVC % and Peak expiratory flow rate (PEFR), to be specific.
      AIMS AND OBJECTIVES: 1. To do a comparative analysis of the PFTs in type 2
      diabetics and non-diabetics by using computerised spirometry. 2. To assess the
      effects of chronic hyperglycaemia on lung functions and functional limitations of
      activities of daily living which are ascribable to pulmonary complications, in
      patients with type 2 diabetes. MATERIAL AND METHODS: Spirometry was performed by
      using a computerised electronic spirometer, (RMS Helios 401, version 3-1-59,
      transducer number 4-16-1669) on 40 type 2 diabetics who were between 40-65 years
      of age and on 40 controls (who were matched for age, sex and BMI). Any person
      with a H/O smoking or any condition which affected the lung functions, was
      excluded from the study. The study was a cross sectional and a retrospective
      study. Data was analyzed and processed with the help of EPI INFO statistical
      software by using unpaired Student's 't'-test (two-tailed). The level of
      significance was taken as a p-value of <0.025. RESULTS: This study clearly showed
      a statistically significant reduction in FVC, FEV1, PEFR in type 2 diabetics as
      compared to those in the controls. FEV1/FVC% was increased in type 2 diabetics as
      compared to that in controls and the increase was statistically significant.
      CONCLUSION: This study concluded that type 2 diabetes adversely affects the
      mechanical functions of the lung, the pattern of disease being primarily
      restrictive in nature.

PMID- 24086853
TI  - Profile of lesions in cystoscopic bladder biopsies: a histopathological study.
AB  - Aim and Introduction: Urinary bladder lesions, non-neoplastic and neoplastic, are
      collectively responsible for significant morbidity and mortality throughout the
      world. The present study aimed to study the histopathology of various lesions of
      the bladder through cystoscopic biopsies. MATERIAL AND METHODS: The present
      prospective study aimed to study the histopathology of various lesions of the
      urinary bladder through cystoscopic biopsies. All patients who visited Urology
      Outpatients Department for haematuria and dysuria were subjected to cystoscopy.
      RESULTS: Histopathological examinations revealed an equal share of non neoplastic
      lesions and neoplastic lesions. Amongst the non neoplastic lesions, 84% were
      inflammatory lesions. Urothelial tumours (96%) formed the bulk amongst neoplastic
      lesions. CONCLUSION: This article has stressed upon the importance of
      histopathological examinations in evaluating bladder pathologies.

PMID- 24086854
TI  - Antibiotic Resistance and Usage-A Survey on the Knowledge, Attitude, Perceptions
      and Practices among the Medical Students of a Southern Indian Teaching Hospital.
AB  - BACKGROUND: Examining the knowledge, attitude, perceptions and practices (KAP) of
      the medical students regarding antibiotic resistance (ABR) and use can help us in
      devising suitable educational interventions for them, tailored according to their
      earlier held knowledge, beliefs, capabilities and experience. METHODS: A cross
      sectional, questionnaire based survey was conducted among the second year medical
      students of a teaching hospital, whereby their KAP regarding antibiotic use and
      resistance was assessed by using a five point Likert scale, whose responses
      ranged from 'strongly agree' to 'strongly disagree,' 'always' to 'never and 'very
      important' to 'unimportant'. The data was analyzed by using simple descriptive
      statistics. Wherever it was relevant, the Chi-square test was used to determine
      any significant difference. RESULTS: The response rate was 100 per cent. The
      number of respondents who agreed that ABR was an important and a serious public
      health issue in our teaching hospital (n= 66, 68 per cent), was significantly
      less (p < 0.001) as compared to the number of respondents who agreed that ABR was
      an important and a serious issue which the country (n = 86, 88.65 per cent) and
      the world (n = 88, 90.7 per cent) were facing. Only 77.3 per cent (n= 75) of the
      respondents were aware that bacteria were not responsible for causing colds and
      flu, while the remaining 22.7 per cent (n = 22) were not knowledgeable about this
      fact. More than 80 per cent rated the adverse effect profile of the antibiotic
      and the risk of a superinfection as the important factors which deserved
      consideration. Cost of the antibiotic was considered to be an important factor
      deserving consideration by only 56.7 percent (n=55) of the participants.
      CONCLUSIONS: Our survey revealed that most of the students were aware of the
      antimicrobial resistance and its consequences. The only concern was their casual
      attitude regarding the antibiotic use. Further educational interventions are
      necessary to improve their understanding and perceptions on antibiotic
      resistance, as well as their attitude towards antibiotic use.

PMID- 24086855
TI  - Study on neuromuscular blockade action of verapamil in albino rats.
AB  - BACKGROUND: Calcium Channel Blockers (CCBs) are now widely employed in the
      treatment of cardiovascular diseases and peri operative hypertension. It has been
      reported that calcium channel blockers inhibit neuromuscular transmission. They
      have been shown to increase the neuromuscular blockade produced by neuromuscular
      blocking agents in in-vitro muscle nerve preparations. The present study is
      undertaken to demonstrate the effect of calcium channel blocker, verapamil on
      neuromuscular transmission in albino rats. OBJECTIVES: To study the neuromuscular
      blockade action of verapamil in albino rats. METHODS: Twenty four albino rats of
      either sex weigh 150-250gms are selected and are randomly divided into 4 equal
      groups. The experimental rats are divided into four groups of 6 rats each and
      they are given the following treatment. Group 1(Control) - Normal saline (1ml/
      kg), Group 2 (Standard) - Pancuronium (0.04 mg/kg) Group 3-Verapamil (2.5mg/kg),
      Group 4-given Verapamil (10mg/kg). The time of onset of hind limb paralysis and
      total duration of recovery are noted using inclined screen method. RESULTS:
      Analysis of the results of group 3 that was received 2.5mg/kg of Verapamil, there
      was no onset of paralysis, in group 4 that received injection Verapamil 10mg/kg,
      showed neuromuscular blockade activity. The mean onset of hind limb paralysis was
      delayed compared to standard group and the mean duration of hind limb paralysis
      was shorter than standard group. It was statistically significant (P<= 0.05).
      INTERPRETATION AND CONCLUSION: It is generally held that external calcium is not
      necessary for the contraction of mammalian skeletal muscle, the demonstration of
      inward calcium currents that can be abolished by CCBs in these muscles prompted
      to re-examine the effect of Verapamil on the neuromuscular transmission. The
      present study allows us to determine the neuromuscular blockade activity of
      Verapamil.

PMID- 24086856
TI  - The prevalence of inducible and constitutive clindamycin resistance among the
      nasal isolates of staphylococci.
AB  - CONTEXT: One of the important sources of Staphylococci which causes nosocomial
      infections, is the nasal carriage of Staphylococci among Health Care Workers
      (HCWs). The commonest antibiotic which is preferred for the treatment of the
      methicillin and multi drug resistant Staphylococcal infections is clindamycin.
      The inducible clindamycin resistance in Staphylococci is not detected by the
      routine antibiotic susceptibility testing and it results in treatment failures.
      AIM: The present study was undertaken to know the prevalence of constitutive and
      inducible clindamycin resistance and its correlation with the methicillin
      resistance among the nasal isolates of Staphylococci which were obtained from
      different HCWs. MATERIAL AND METHODS: Nasal swabs were collected from 206 HCWs
      and they were processed. The Staphylococci which were isolated were tested for
      methicillin resistance by using cefoxitin (30 MUg) discs. The inducible
      clindamycin resistance was tested by using erythromycin (15 MUg) and clindamycin
      (2MUg) discs and the D test according to the CLSI guidelines. RESULTS: Inducible
      clindamycin resistance was seen in 21(16.40%) of the S.aureus and 14 (7.56%) of
      the coagulase negative Staphylococcal isolates. Constitutive clindamycin
      resistance was seen in 23(17.96%) of the S.aureus and 43(23.24%) of the coagulase
      negative Staphylococcal isolates. The inducible and constitutive clindamycin
      resistance was more common among the methicillin resistant Staphylococcal
      isolates. CONCLUSION: The prevalence of inducible and constitutive clindamycin
      resistance in the nasal Staphylococcal isolates which were obtained from the HCWs
      was high, especially among the methicillin resistant Staphylococci. The D test
      which is recommended by the CLSI should be routinely done to detect inducible
      clindamycin resistance, to prevent treatment failures.

PMID- 24086857
TI  - Human immunodefeciency virus associated cryptococcal meningitis at a tertiary
      care centre: diagnostic tools and antifungal susceptibility testing.
AB  - CONTEXT: Cryptococcal meningitis has emerged as a leading cause of the infectious
      morbidity and mortality in HIV sero-reactive subjects and it is the second most
      common cause of the opportunistic neuroinfections in it. As this is a
      indistinguishable from other causes of meningitis, its early diagnosis is the key
      to the therapeutic success. OBJECTIVES: This study was undertaken to know the
      incidence of Cryptococcal meningitis in HIV sero-reactive individuals and to
      assess the role of the microbiological parameters in its specific diagnosis, with
      a perspective of evaluating the anti-fungal resistance. MATERIAL AND METHODS: A
      total of 66 CSF samples from suspected cases of meningoencephalitis were
      subjected to standard microbiological procedures. The Cryptococcal isolates were
      identified by microscopy, the cultural characteristics, melanin production on
      Niger Seed agar, urea hydrolysis, the Nitrate assimilation test and by capsular
      antigen detection by latex agglutination. The Cryptoccal isolates were further
      biotyped by using Canavanine-Glycine-Bromothymol blue agar. The Minimum
      Inhibitory Concentrations (MIC) of Amphotericin B and Fluconazole for the
      isolates were detected. RESULTS: The incidence of Cryptococcal meningitis in our
      study group was 18.2% (12/66). The Cryptococcal antigen was detected in all the
      12 cases, whereas microscopy was positive only in 9 cases and Cryptococcus was
      isolated by culture in 10 cases. All the isolates were sensitive to Amphotericin
      B and 90% of the isolates were sensitive to Fluconazole. The CD4counts ranged
      between 22-138 cells /MUl. CONCLUSION: A high incidence of Cryptococcal
      meningitis in HIV sero-reactive subjects necessitates the importance of a precise
      and an early microbiological diagnosis for better management of such subjects.
      Due to the growing concern of emerging drug resistance, the testing for the anti
      fungal susceptibility has to be encouraged in all the cases.

PMID- 24086858
TI  - Herpes Simplex Encephalitis (HSE) and its outcome in the Patients who were
      Admitted to a Tertiary Care Hospital in Mashhad, Iran, over a 10-year Period.
AB  - INTRODUCTION: The effective cure rate of acyclovir emphasizes the importance of
      an early diagnosis and treatment in reducing the considerable mortality and the
      morbidity in patients with Herpes Simplex Encephalitis (HSE). METHODS: The
      demographic as well as clinical features, the lab data and the neuroimaging
      findings of the patients with HSE, which were confirmed by Cerebrospinal Fluid
      (CSF) PCR and/or brain MRI, were reviewed and analyzed statistically over a 10
      year period. RESULTS: Over a 10-year period, the characteristics of 45 patients
      with HSE were reviewed. 34 (76%) out of the 45 patients showed positive CSF HSV-1
      PCR results. 8 (18%) had a normal CSF analysis and a CSF/blood glucose ratio of
      less than 0.5 was observed in 13 (29%) patients, while 14% had PMN-dominant
      pleocytosis. 68% of the patients for whom brain MRI was performed, had temporal
      lobe involvement. While 37 (83%) patients recovered completely, 6 (13%) survived
      with sequelae, and 2 (4%) died. CONCLUSION: Because of the increasing number of
      atypical forms of HSE and the great impact of an early diagnosis and treatment on
      a favourable outcome, the acyclovir therapy should be administrated for any type
      of febrile encephalopathy of unknown aetiology, until HSE can be excluded.

PMID- 24086859
TI  - The association of positive chest radiograph and laboratory parameters with
      community acquired pneumonia in children.
AB  - CONTEXT: This study was designed to compare the sensitivities of different
      investigations for the diagnosis of Community Acquired Pneumonia (CAP). A
      prospective study was carried out which compared the sensitivities of the chest
      radiographs, CRP, TLC, ESR and the blood cultures in sixty-six patients who were
      diagnosed with WHO defined CAP. METHOD AND MATERIAL: The chest radiographs, serum
      C-reactive protein (CRP), erythrocyte sedimentation rate (ESR), total leucocyte
      count (TLC) and blood cultures were determined in sixty-six patients who were
      amongst the age group of one month to five years of age, who were diagnosed with
      WHO defined CAP. STATISTICAL ANALYSIS: It was carried out by calculating the
      proportion, mean, standard deviation (SD) and the sensitivity of the test/.able
      RESULTS: The chest radiographs were found to be positive in 93.9% (n=62)
      patients, CRP was positive in 90.9% (n=60) patients, ESR was positive in 72.7%
      (n=42) patients, TLC was positive in 48.5% (n=38) patients and the blood cultures
      were positive in 6.1% (n=4) patients. Hence, the sensitivity of the chest
      radiograph, CRP, ESR, TLC and the blood culture in the diagnosis of CAP were
      93.9%, 90.9%, 72.7%, 48.5% and 6.1%. CONCLUSION: In view of the high sensitivity
      of CRP, which is almost similar to that of chest X-Ray in detecting CAP, CRP can
      be used as an alternative test to the chest radiographs at peripheral centres,
      where X-ray machines are not available.

PMID- 24086860
TI  - Prevalence, pattern and familial effects of substance use among the male college
      students -a north Indian study.
AB  - INTRODUCTION: Substance use refers to the use of any psychoactive substance or
      drug, including licit and illicit drugs, other than when medically indicated.
      Psychoactive substance use poses a threat to the health, social and economic
      fabric of families, communities and nations. Chandigarh has more than 0.2 million
      students from across the country pursuing their courses in higher education
      institutions. There is a very little information about pattern of drug dependence
      among the college students of Chandigarh,India. OBJECTIVES: To study the
      prevalence and pattern of substance use among college students of Chandigarh and
      to study the psycho-social behaviour of youth and perceived reasons for using
      substances. MATERIAL AND METHODS: A Cross - sectional community based study. A
      stratified multi-stage random sample design was adopted in study. The study
      instrument was a questionnaire which was developed by reviewing relevant
      literature and previously used standardized instruments and protocols including
      the WHO questionnaire. On the basis of 60% prevalence anticipated on the basis of
      pilot study, 90% confidence coefficient and 10% permissible error - sample size
      came out to be 256. RESULTS: Prevalence of substance use was seen in 52.7%
      students belonging to age group 19 to 21 years. More prevalence of substance use
      was found among law students (76.2%) followed by the students from Art stream
      (62.5%). Among the users alcohol was most commonly used (53.5%), followed by
      smokers (27.3%), tobacco chewers (8.2%), cannabis (6.8%).49% of the users were
      using substances on daily basis, followed by 23% who using weekly.29.3% of users
      had father using any substance. Relief from psychological stress (66.0%) followed
      by easy availability (46.9%) were the most common reasons of substance abuse.
      that substances use is common among college going male students irrespective of
      their social demographic characteristics like age [OR 0.76, 95%CI (.443-1.317)
      religion [OR.859 95%CI (.461-1.598), parental education, occupation and socio
      economic status. Therefore, interventions in terms of health
      education/counselling for reducing substance use among them should be adopted,
      irrespective of their socio-demographic characteristics. Suggestions: This study
      suggested some life style related interventions in order to reduce the problem of
      substance use.There is an utmost need to educate and counsel young students
      regarding harmful effects of substance use. Health education may be imparted in
      the school curriculum. Parents should also be educated on discouragement of
      substance use and on taking proper care of their children.

PMID- 24086862
TI  - Family planning practices prior to the acceptance of tubectomy: a study among
      women attending a maternity home in bangalore,india.
AB  - INTRODUCTION: The extent of acceptance of contraceptive methods still varies
      within societies. Reliance on sterilisation is appearing earlier in marriage and
      among ever-younger ages and lower parities. AIM AND OBJECTIVE: To study the
      family planning practices adopted by women who undergo tubectomy before the
      acceptance of tubectomy. MATERIAL AND METHODS: Cross-sectional study of tubectomy
      acceptors who attended a corporation referral maternity home in Bangalore, India
      by interview method using a pre-designed a pre-tested structured questionnaire.
      RESULTS: Majority 295(73.9%) of the study subjects had not practised any method
      of contraception before they underwent sterilisation. Increase in the education
      levels of the study subjects was associated with an increase in the contraceptive
      use (temporary methods) before they accepted tubectomy; this association was
      found to be statistically significant (p<0.0001).

PMID- 24086861
TI  - Prevalence and Pattern of Alcohol Consumption using Alcohol Use Disorders
      Identification Test (AUDIT) in Rural Tamil Nadu, India.
AB  - BACKGROUND: There is a paucity of information on prevalence and pattern of
      alcohol consumption in India. AIM: To assess the prevalence and pattern of
      alcohol consumption in a rural area of Tamil Nadu, India. MATERIAL AND METHODS: A
      community based, cross sectional study was conducted among 946 subjects who were
      aged 10 years and above, in rural Tamil Nadu, India. Data on alcohol use was
      collected by using 'Alcohol Use Disorder Identification Test' (AUDIT) scale. Data
      on pattern and associated factors like socio-demographic details, smoking,
      tobacco chewing and chronic diseases were collected by using a structured
      questionnaire. STATISTICAL ANALYSIS: Data was analysed by univariate and multiple
      logistic regression analysis and information was depicted in percentages or
      proportions. A p value of less than 0.05 was considered as significant. RESULTS:
      Overall, the prevalence of alcohol use was found to be 9.4%. Prevalence was more
      among males (16.8%) as compared to that among females (1.3%). Mean age at
      initiation was 25.3 +9.0 years. Multiple logistic regression analysis revealed
      that middle age (15-44 years) (OR=3.56), male gender (OR=11.23), illiteracy
      (OR=6.16), lower education levels (OR=2.57) and smoking (OR=17.78) were
      independently associated with alcohol use. Among those who used alcohol, 29.2%
      (26) were possible hazardous drinkers, 33.7%(30) had a probable alcohol
      dependence and 56.2% (50) had experienced harmful effects, based on AUDIT item
      analysis. CONCLUSION: Prevalence of alcohol use is high, especially among males.
      Health educational interventions among those who are at a higher risk and
      management of alcohol dependent subjects, may help in reducing the burden of
      alcohol use in this area.

PMID- 24086863
TI  - Determination of Sites Involved, HIV Co-Infection & Utility of Diagnostic
      Modalities in EPTB.
AB  - BACKGROUND: Tuberculosis remains a major global public health problem and an on
      going epidemic. Though the chief objectives of the Revised National Tuberculosis
      Control Programme (RNTCP) in detecting and curing the infectious pulmonary cases
      is well taken, there has been a steady rise in the number of Extra Pulmonary
      Tuberculosis (EPTB) cases as documented in several studies. EPTB which usually
      constitutes around 15%-20% of the total TB cases is now being increasingly
      reported due to a combination of better diagnostic facilities, and the HIV
      pandemic. Though several studies have shown increasing prevalence of EPTB, only
      few studies are available, especially in the Indian scenario, that study the
      pattern and risk factors. Hence, this retrospective observational study was
      undertaken to determine the sites of the involvement, HIV co-infection and
      usefulness of various diagnostic modalities in EPTB affecting patients attending
      a medical college DOTS clinic. MATERIAL AND METHODS: One hundred ten EPTB
      patients referred to the DOTS clinics of the TB & Chest department from the
      period Dec 2010- Mar 2012 were included in the study. The diagnosis of EPTB was
      established by combined clinical, microbiological, histopathological &/or imaging
      modalities. Their medical records were assessed to determine the age
      distribution, gender and anatomical sites of involvement. The presence of co
      morbid conditions like smoking history, alcoholism, diabetic and HIV status were
      noted. BCG status and Mantoux test readings were recorded. The different
      diagnostic tests used in confirming EPTB at different sites were recorded. Chest
      x-ray was analysed for all patients to assess coexisting pulmonary involvement.
      All patients were followed to assess the outcome of treatment. RESULTS: The mean
      age of patients was 34.4. The male to female ratio was 58:52 showing a slight
      male predominance. The most common site of involvement was lymph node followed by
      pleural effusion and abdominal TB. The prevalence of lymph node TB was noted to
      be higher in female patients as compared to other sites of EPTB. Mantoux test was
      positive in 57 (51.8%) patients. HIV co-infection was noted in only 3 (2.7%)
      patients. Concomitant pulmonary involvement was seen in 19 (17.3%) patients.
      CONCLUSIONS: Lymph node was the most common site involvement showing a
      significant female preponderance followed by pleural effusion and abdominal TB.
      The rates of HIV co-infection and diabetes mellitus were 2.7% and 20%
      respectively. The most useful diagnostic modality was tissue sampling followed by
      imaging. Mantoux test is not unequivocal for the diagnosis of EPTB.

PMID- 24086864
TI  - Platelet functions and coagulation changes in Indian children with nephrotic
      syndrome.
AB  - INTRODUCTION: Only little is known on the effect of the platelet function in the
      paediatric nephrotic syndrome. The earlier studies which had been done on
      hypercoagulability have mainly featured the secondary forms of the nephrotic
      syndrome and the data on the minimal change type of disease is limited. We
      therefore, made an effort to study the platelet functions and the coagulation
      profile in children with the nephrotic syndrome,to find the relationship between
      the steroid response and the coagulation profile, and to look for the correlation
      between thromboembolism and the hypercoagulable states. METHODOLOGY: Twenty nine
      children with the steroid responsive nephrotic syndromewere studied to see the
      platelet aggregation and the coagulation parameters and their response to the
      steroid therapy. Doppler studies were done for the renal vein and the inferior
      vena cava (IVC) thrombus. RESULTS: It was seen that an increased aggregability of
      the platelets occurred with Adenosine diphosphate (ADP) and collagen (out of the
      four agonists, ADP, Collagen, Ristocetin and Arachidonic acid) which were used as
      agonists for the assay. We also observed that the Partial thromboplastin time
      (PTT) had become prolonged and a significant decline in the high values of the
      procoagulant proteins (Protein C and Protein S) was seen after the steroid
      therapy and when the children went into remission. These findings were suggestive
      of a reversibility of the changes in the steroid responsive nephrotic syndrome
      with the steroid therapy. One child was found to have thrombosis of the inferior
      vena cava (IVC) on Doppler studies, which resolved with treatment subsequently.
      CONCLUSIONS: An increased platelet aggregability contributes to the
      hypercoagulable states, that may increase the incidence of thrombosis in such
      patients. Although the incidence of such complications is very low, in a given
      child with the hypercoagulable states, Doppler may be used to look for any
      evidence of a latent thrombus and, an early intervention could be instituted. A
      change in the coagulation parameters points to the reversibility of the changes
      which are produced in a diseased state.

PMID- 24086865
TI  - Cardiac blood flow measurements in stable full term small for gestational age
      neonates.
AB  - BACKGROUND: Cardiac blood flow measurements are useful in the haemodynamic
      management of neonates. Cardiac blood flows can be estimated with functional
      echocardiography as follows; flow in Superior Vena Cava (SVC), Right Ventricular
      Outflow (RVO) and Left Ventricular Outflow (LVO). Studies in preterm infants have
      shown that abnormal superior vena cava flow is associated with poor
      neurodevelopmental outcomes. To date, normative data on LVO, RVO and SVC flows
      has been established for term appropriate for gestational age neonates and
      preterm neonates, but no data is available on RVO, LVO and SVC flows for term
      small for gestational age neonates. OBJECTIVE: To determine Right Ventricular
      Output (RVO), Left Ventricular Output (LVO) and Superior Vena Cava (SVC) flow
      after the transitional period in stable full term Small for Gestational Age (SGA)
      neonates. DESIGN: Observational study. SETTING: A tertiary care, perinatal centre
      in western Maharashtra, India. PARTICIPANTS: Full term (37 to 41 weeks) small for
      gestational age (weight below 10th percentile for gestational age) infants who
      were born during the study period. METHODS: RVO, LVO and SVC flows were measured
      by functional echocardiography on day 7 of life in stable full term SGA neonates
      from January 2011 to August 2011. Infants who required respiratory or
      cardiovascular support and intensive care unit admissions for any indication and
      those with a clinical suspicion of an infection within 48 hours after data
      collection were excluded from the study. STATISTICAL ANALYSES: Unpaired t-test
      was used to compare SVC flow between symmetric and asymmetric SGA neonates. MAIN
      OUTCOME MEASURE: Measurements of RVO, LVO and SVC in term SGA neonates on day 7
      of life. RESULTS: We performed measurements in 52 term SGA neonates with a median
      (range) birth weight of 2.190 (1.600-2.410) kg. Fifty two measurements were
      analyzed on day 7. The mean (SD) RVO, LVO and SVC flows were 255.59 (57.42) ,
      214.61 (52.04) and 126.28 (31.23) mL/kg/min. CONCLUSION: This study provides RVO,
      LVO and SVC flow values in a cohort of stable term SGA neonates after the
      transitional period.

PMID- 24086866
TI  - Determinants of urea production and mineral retention in parenterally fed preterm
      infants.
AB  - OBJECTIVE: To determine how weight for gestational age affects urea and mineral
      excretion by preterm infants receiving total parenteral nutrition (TPN). STUDY
      DESIGN: Daily urine samples were collected from all preterm infants given high
      calcium TPN, providing 30 kcal/g amino acids, during its first 44 months of use,
      and from all those given standard TPN, providing 25 kcal/g amino acids, over the
      previous 24 months. Urine urea and mineral excretion were measured as follows:
      Urea excretion mmol/kg/day = Urine urea/urine creatinine X creatinine production
      Creatinine production MUmol/kg/day = -2.07 + 2.34 X gestational age in weeks
      Results: High calcium TPN was evaluated in 52 infants. Urea excretion did not
      rise with increasing TPN intake. During the first week, urea excretion increased
      with weight for gestational age, with higher rates in above average than below
      average weight infants. It also increased with gestational age in above average
      but not below average weight infants. Below average weight infants had lower
      potassium and phosphate excretion than those above average. Standard TPN was
      evaluated in 20 infants. Urea excretion increased with TPN intake to higher
      levels than on high calcium, and also increased with weight for gestational age.
      CONCLUSION: Urea excretion was simple to measure, with remarkably consistent
      daily results in individuals. Below 30 weeks gestation infants on TPN providing
      30 kcal/g amino acids had urea excretion < 0.1 g urea N/kg/day, < 3.5 mmol/kg/day
      if below average weight, and < 0.12 g urea N/kg/day, < 4.3 mmol/kg/day if above
      average weight. Below average weight infants retained more potassium and
      phosphate during the first week than those above average, and their greater
      requirements were provided by the TPN.

PMID- 24086867
TI  - Pregabalin in Chronic Post-thoracotomy Pain.
AB  - INTRODUCTION: Chronic post-thoracotomy pain (CPP) has very high incidence and
      therefore it needs attention. Usually, it is burning, dysaesthetic and aching in
      nature and it displays many features of neuropathic pain. No one technique of
      thoracotomy has been shown to reduce the incidence of chronic post thoracotomy
      pain. OBJECTIVES: To evaluate the efficacy and safety of pregabalin in patients
      with chronic post-thoracotomy pain. METHODS: This prospective, randomized study
      was conducted on 50 consenting patients who underwent posterolateral thoracotomy.
      25 patients were given pregabalin for 21 days (Group A). Another 25 were given
      diclofenac sodium (Group B) on demand and they escaped treatment. Visual Analogue
      Scale (VAS) scoring was performed on days 0, 1 and 7, then follow up was done at
      3, 6, 12 and 24 weeks. The data was analyzed by using t-test and Chi- square test
      for various variables. RESULTS: The pain VAS scores in Group A were significantly
      low at all observation points except on day 0, day 1 and day 7 post-operatively,
      when the difference in pain scores in both the groups were comparable. The
      overall pain scores of Group A were comparable at day 0, day 1 and at day 7 as
      compared to those of Group B (p>0.9). Pain was significantly low at three weeks
      (p<0.05). Pain scores of Group A were significantly low at 6 weeks,12 weeks and
      24 weeks as compared to those of Group B (p<0.001) and the difference was
      statistically significant. No significant adverse reactions were observed during
      study period. CONCLUSION: Pregabalin is a safe and an effective adjuvant which is
      used for reducing the chronic post thoracotomy pain, which has no side effects
      and a high patient compliance. These results should be supported with
      multidisciplinary studies with larger sample sizes and longer follow-ups.

PMID- 24086868
TI  - Necrotising soft tissue infection-risk factors for mortality.
AB  - Necrotising Soft Tissue Infection is a rapidly progressing fatal disorder, the
      prognosis of which depends on early diagnosis and management. OBJECTIVE: In this
      study, our objective was to assess the factors contributing to mortality due to
      NSTI. METHODS: A retrospective review of the records of all patients with NSTI
      involving fascia, skin or muscle between January 2007 and December 2011, was
      performed. The atiology, predisposing factors, risk factors, causative
      microbiological organisms and the clinical outcomes associated with mortality
      were studied. Statistical Data: Descriptive statistics comprising of
      proportion(%) presented. Chi-square test was employed to assess the statistical
      significance in the distribution of various known risk factors between the
      survivors and non-survivors. A 'p' value less than 0.05 was considered
      significant. RESULTS: Sixty patients records were reviewed. Fifty-one patients
      (85%) were males and nine (15%) were females. Mean age was 46.57 years (+/-
      20.60) ranging from 15-83 years. All the patients were treated by debridement &
      wide spectrum antibiotics. Mono-microbial atiology being found in 27 patients
      (63.3%) and polymicrobial culture was isolated in 13 patients (36.7%), with E
      coli and staphylococci being the most common organisms to be isolated. In most
      patients, multiple debridements were done. The overall mortality rate was
      estimated to be 25%. Age, aatiology, diabetes mellitus, hypoalbuminemia, alcohol,
      site of infection, bacteriology etc. were the risk factors associated with
      mortality, that were evaluated. Diabetes mellitus was the most common associated
      risk factor found in 32 patients (53.3%), though not statistically significant.
      Increasing age (>50 years, p value = 0.016), raised Serum Creatinine (>1.2mg/dl,
      p-value = 0.023) and delayed surgical intervention(>24 hours p value= 0.006) were
      the risk factors associated with Mortality in NSTI that were statistically
      significant. CONCLUSION: Despite the use of appropriate antibiotic treatment,
      aggressive debridement & resuscitation, NSTI still leads to a high mortality &
      morbidity. In this series, there is high mortality associated with increasing
      age, raised serum creatinine and delayed surgical intervention. The mortality
      rate (25%) is comparable with other studies.

PMID- 24086869
TI  - Closed reductions and percutaneus 'k' wire fixation for adolescent intercondylar
      fractures of the distal humerus.
AB  - INTRODUCTION: Intercondylar (T-Condylar) fractures of the humerus are very rare
      in children. The usual mechanism of the injury which is involved is a fall on a
      flexed elbow. The treatment options vary, depending upon the degree of the
      displacement and the amount of comminution and; they may range from a simple
      application of traction to open reduction and internal fixation with plates and
      screws. Open reduction is associated with significant post-operative stiffness of
      the elbow and subsequent less than satisfactory functional results. In this
      publication, we are presenting our experience of treating seven adolescent T
      Condylar fractures of the distal humerus with closed reductions and internal
      fixations with the percutaneus Kirchner ('K') wire. METHOD: Seven patients (M:F
      6:1) with an average age of 14(range 12-16) years were treated by closed
      reduction and internal fixation with a 2.0 mm 'K' wire fixation under an image
      intensifier. Following the surgery, all the elbows were immobilised in plaster of
      Paris (POP) splints for three weeks. At three weeks after the surgery, the pop
      splints were removed and gentle elbow exercises were started. Five weeks after
      the surgery, the 'K' wires were removed, based on the radiological evidence of a
      bridging callus formation. RESULTS: Six patients (85%) out of seven showed
      satisfactory functional results on the Mayo Elbow Performance Score (MEPS), with
      a good range of motion at the elbow joint. Three (42%) patients had mild elbow
      stiffness, which resolved on subsequent treatment, while one (14%) had a mild pin
      tract infection, who was managed conservatively. There was one patient (14%) who
      was lost to follow-up, who ultimately had a painful and a stiff elbow. The
      remaining six patients were able to return to the premorbid sate. CONCLUSION: We
      recommend closed reduction and percutaneous 'K' wire fixation for adolescent T-
      Condylar fractures of the humerus as an easy and inexpensive procedure with
      satisfactory functional results.

PMID- 24086870
TI  - Bipolar hemiarthroplasty in unstable intertrochanteric fractures in elderly: a
      prospective study.
AB  - INTRODUCTION: Intertrochanteric fractures in osteoporotic bones which are grossly
      comminuted are highly unstable and difficult to treat. Conservative treatment
      with traction and prolonged immobilization lands up with many complications and
      often fatality. Rate of failure with internal fixation, with dynamic hip screws
      has been found to be high, especially in osteoporotic bones. Revision
      osteosynthesis is technically demanding and it leads to complications. The aim of
      this study was to assess the efficacy of cemented hemiarthroplasty in the
      management of proximal femoral fractures in elderly patients with severe
      osteoporosis. MATERIAL AND METHODS: Twenty patients (11 males and 9 females- all
      were 65 years old or above) who underwent bipolar arthroplasty for unstable
      intertrochanteric fractures were prospectively evaluated. Moore's approach was
      used in all patients. Greater Trochanter encirclage was done in 10 (50%)
      patients. Harris hip score was used for the clinical evaluation. The mean follow
      up period was 9 months. RESULTS: In our study which was done on 20 cases which
      had a mean age 72.4 years, 14 cases were of type 2 fractures, 3 were of type 3, 2
      were of type 1 fractures and 1 was of type 4. The average Harris hip score was
      75. Excellent to fair results were obtained at follow-up in 18 (90%) cases and in
      2 (10%) cases, the results were poor. Average hospital stay was 13.3 days. There
      was one case of a superficial operative site infection and one case of a deep
      infection. There was no case with loosening of the prosthesis, break in the
      cement or sinking of the prosthesis. CONCLUSION: The treatment of unstable
      intertrochanteric fractures in elderly patients with severe osteoporosis differs
      from the treatment of patients with other proximal femoral fractures. These
      fractures are better treated with cemented hemi-arthroplasty than with internal
      fixation. Besides an early ambulation and less hospital stay, cemented hemi
      arthroplasty provides stable and mobile hips. Weight bearing can be started
      earlier than in other methods of treatment, which prevents any recumbency related
      complications.

PMID- 24086871
TI  - Comparing the efficacy of tamsulosin and silodosin in the medical expulsion
      therapy for ureteral calculi.
AB  - BACKGROUND: Urolithiasis is a chronic disease of mankind, which has enormous
      public health importance and it accounts for a substantial economic burden on our
      society. Hence, it becomes all the more important to formulate cheaper and easier
      means for treating this condition. The past few years have seen a number of drugs
      being introduced and successfully used in the medical expulsion therapy of small,
      uncomplicated ureteral calculi, with each drug claiming to provide better results
      than the others. Ours is perhaps the first study which has compared the efficacy
      of tamsulosin and silodosin in the medical expulsion therapy for ureteral
      calculi. AIMS: To compare the efficacy of tamsulosin (0.4mg) vs silodosin (8mg),
      both in terms of the stone expulsion rate and the time to stone expulsion.
      SETTINGS AND DESIGN: A prospective and a randomized controlled study was
      conducted in the Department of Urology, Regional Institute of Medical Sciences
      (RIMS), Imphal, Manipur, India. MATERIAL AND METHODS: From February to August
      2012, 100 patients who were between the age group of 18-50 years, who had
      unilateral, uncomplicated middle or lower ureteral stones </= 1cm were enrolled
      and they were divided into two groups. Group 1 received tamsulosin (0.4mg) daily,
      whereas Group 2 received silodosin (8mg) daily for a maximum period of 4 weeks.
      The patients were followed up weekly or biweekly with imaging studies. The
      primary endpoint was the stone expulsion rate and the secondary endpoints were
      the stone expulsion time, the rate of the interventions and the side effects.
      STATISTICAL ANALYSIS: The statistical analysis was performed by using the
      Student's t-test and the Chi-squared test. A p value of < 0.05 was considered to
      be statistically significant. The SPSS-16 software was used for the statistical
      analysis of the data. RESULTS: A spontaneous stone expulsion was observed in 58%
      of the patients in group 1 and in 82% of the patients in Group 2, which was
      statistically significant. There was also a significant difference between the
      groups with regards to the mean stone expulsion time. A lower analgesic use was
      found in Group 2. CONCLUSION: In our study, silodosin was found to be clinically
      superior to tamsulosin, both in terms of the stone expulsion rate and the stone
      expulsion time.

PMID- 24086872
TI  - Umbilical cord coiling index and perinatal outcome.
AB  - OBJECTIVES: To evaluate the perinatal outcome with the abnormal umbilical cord
      coiling index. STUDY DESIGN: This prospective study was carried out in the
      department of OBG at Adichunchangiri Institute of Medical Sciences, B.G.Nagara,
      Mandya, Karnataka, India from January 2008 to August 2010. 200 patients who were
      in active labour with term gestations, irrespective of their parities, who had
      singleton pregnancies with live babies who were either delivered by vaginal or
      LSCS were included in the study. Umbilical cord coiling index was calculated and
      it was correlated with various perinatal parameters like birth weight, meconium
      stained liquor, Apgar score, ponderal index and foetal growth restriction. Chi
      square and Fisher exact tests were used to find the significance of study
      parameters. RESULTS: There was a significant correlation between the hypercoiled
      cords (UCI >90(th) percentile) and IUGR of the babies (p value of < 0.001) and
      low ponderal indices (a p value of 0.022) Hypocoiled cords ( UCI which was <
      10(th) percentile) were significantly associated with meconium staining (p <
      0.001), Apgar score at 1 min of <4 and at 5 min of <7 (p value 0.065), LSCS rates
      (p value of 0.008) and NICU admissions (p <0.001). CONCLUSION: Hypercoiled cords
      or UCI which was > 90(th) percentile was associated with IUGR and low ponderal
      indices. Hypocoiled cords or UCI which was <10th percentile was associated with
      meconium staining, Apgar score at 1 min of <4 and at 5 min of <7, more LSCS rates
      and more NICU admissions.

PMID- 24086873
TI  - The Incidence of Hyponatraemia and Its Effect on the ECOG Performance Status
      among Lung Cancer Patients.
AB  - CONTEXT: Hyponatraemia is one of the common electrolytic disorders which are
      associated with lung cancer. Hyponatraemia may influence the ECOG performance
      status at presentation. Also, to the best of our knowledge, we found only limited
      Indian studies where the ECOG score was correlated with the serum sodium status
      in lung cancer patients on presentation. AIM: To assess the incidence of
      hyponatraemia among the patients of carcinoma of the lung before putting them
      into the specific treatment category for cancer and to check the effects on their
      ECOG performance status. SETTINGS AND DESIGN: A cross-sectional, observational
      study was conducted on 116 consecutive patients of lung cancer during the period
      from November 2011 to October 2012. MATERIAL AND METHODS: The patients with a
      histologically proven diagnosis of lung cancer were grouped initially according
      to their ECOG performance statuses. The serum sodium value of each patient was
      measured and the hyponatraemic patients were given treatment according to the
      protocol. The correlation of the ECOG performance status with the serum sodium of
      the lung cancer patients was measured. To check for any laboratory error in serum
      sodium, we selected (n = 58) age, sex and socioeconomic matched control patients.
      RESULTS: At presentation 44.8% of the lung cancer patients showed hyponatraemia
      [52/116]. The ECOG score was significantly poor in the advanced clinical stages
      (ECOG <=2 Vs ECOG >= 3 in NSCLC cases, chi(2) =11.25, P=.0008). The ECOG
      performance status score at admission showed a negative correlation with the
      serum sodium status which was measured on admission among all the patients
      (Pearson correlation coefficient = - 0.186). The clinical stage of the lung
      cancer also showed a positive correlation with the ECOG score at admission in our
      study (Pearson correlation coefficient = 0.295). CONCLUSION: Hyponatraemia is not
      an uncommon condition and it should be suspected and screened in each patient, as
      it may influence the ECOG performance status score, which serves as an important
      factor in the prognosis of lung cancer.

PMID- 24086874
TI  - The perceptual preferences in learning among dental students in clinical
      subjects.
AB  - INTRODUCTION: VARK is a questionnaire which was developed by Neil Fleming
      (www.vark.learn.com), who was a teacher and an educator in New Zealand, with
      respect to the perceptual preferences in learning. V stands for Visual- the
      students learn best from pictures, graphs and diagrams. A stand for Aural - the
      students learn best from spoken words, lectures and discussions. R stands for
      Reading - the students learn best from reading and writing texts. K stands for
      Kinesthetic - the students learn best when they move their bodies and manipulate
      things with their own hands. AIM: The aim of the recent study was to investigate
      the learning styles among the dental students in our clinical set up. METHOD: The
      VARK-questionnaire contains 13 multiple-choice- questions with four possibilities
      to select an answer. Each possibility represents one of the four modes of
      perception. But, one can select more than one answer for each question, which is
      necessary for the identification of the poly modal modes of perception and
      learning. This is also a psychometric problem when an attempt is being made to
      state a measure of the reliability of the questionnaire. The VARK-questionnaire
      was distributed among 100 students and we received filled forms from only 70
      students. This sample size represented a 70% response rate from the students in
      the class and it was markedly above the level which was required to make
      conclusions about the student preferences for receiving and processing
      information. The students spent about 10 minutes in an ordinary lesson to fill in
      the questionnaire. The students' register numbers and names were used in the
      study and no blinding was practised. We analyzed their learning styles with their
      performances in the university exams. STUDY DESIGN: This was a questionnaire
      based clinical study. RESULTS: The responses from the students in our University
      where classified into the multi-modal (VARK), tri-modal (VRK, VAK, VAR, ARK), bi
      modal (VR, VA, VK, RK) and the uni-modal (V, A, R.K) categories. The results
      showed that the subjects had a higher preference for multimodal learning.
      CONCLUSION: With our preliminary data, we conclude that the students in our
      clinical set up preferred a multimodal and a more of kinesthetic method of
      learning. To meet their needs, variations in the teaching, learning and the
      examination must be implemented. If not, the students with a high kinesthetic
      preference for perception and learning may be at the losing end.

PMID- 24086875
TI  - An autopsy study of liver injuries in a tertiary referral centre of eastern
      Nepal.
AB  - BACKGROUND: Liver is the largest gland in the body and it frequently gets
      wounded. The objective of this study was to determine the patterns, types and
      severities of liver injuries which were caused by mechanical trauma and to study
      the organs associated with liver injuries. MATERIAL AND METHODS: This was a
      hospital based, cross sectional study which was conducted on the autopsies
      showing the evidence of liver injuries in the mortuary of a tertiary hospital in
      eastern Nepal. All consecutive autopsy cases which were handled within one year's
      time (n=46) were included in our study. The cases were studied in detail for
      liver injuries, which included age, sex, severity, associated injuries, site of
      the injury, description of the injury, etc. RESULTS: The mean age of the victims
      was 33.87 years and there was a male: female ratio of 3.6:1. The injuries had
      resulted from blunt trauma in 41 (89.1%) cases, the most common of which was road
      traffic accidents, constituting 37(80.4%) cases. Grade III injuries were seen in
      14 (30.4%) cases. Laceration of the liver was the most frequent finding that was
      evident in 34 (73.9%) cases. Right lobe of the liver was injured in 30 (74%)
      cases. The sole presence of liver injuries among abdomino-pelvic organs was seen
      in 14 (30.4%) cases. In 40 (87%) cases, liver injuries were associated with other
      regional injuries. CONCLUSION: Laceration is the most common liver injury among
      autopsy cases. Right lobe is mostly affected and grade III injuries are the most
      common ones. Liver injuries are frequently associated with other abdomino-pelvic
      organs and multiple regional injuries.

PMID- 24086876
TI  - Pattern of psychiatric referrals in a tertiary care teaching hospital in southern
      India.
AB  - BACKGROUND: There is a dearth of studies which are related to consultation
      liaison psychiatry in India. The psychiatric referral rates in India are very
      low, considering the higher rates of psychiatric morbidity in patients who attend
      various departments of a hospital. Studying the pattern of psychiatric referrals
      may pave the way for interventions to improve the current scenario. METHODS: The
      study population comprised of all the patients who were referred for psychiatric
      consultation from other departments (both in-patient and out-patient) of the
      hospital over a period of two years. Data which was related to socio-demographic
      profile, source of referral, reason for referral and the psychiatric diagnosis
      were recorded and analyzed by using descriptive statistical methods. RESULTS: A
      total of 520 patients were referred for psychiatric consultation, with a referral
      rate of 0.42%. A majority of the psychiatric referrals (59%) were from the
      department of medicine and the most common reason for referral was medically
      unexplained somatic complaints (23.1%), followed closely by anxiety (21%) and
      abnormal behaviour (13.1%). The most commonly diagnosed psychiatric disorders
      were neurotic, stress related and somatoform disorders (41.7%) followed by mood
      disorders (12.9%) and substance use disorders (12.7%). CONCLUSION: There is a
      need to encourage multi-disciplinary interaction in the management of patients
      who attend general hospitals, so as to better identify the psychiatric morbidity.
      Further studies should focus on interventions that can improve referral rates
      through early recognition of the common psychiatric conditions, with particular
      emphasis on sensitizing the general physicians, who are the most common source of
      psychiatric referrals.

PMID- 24086877
TI  - Kocuria kristinae in catheter associated urinary tract infection: a case report.
AB  - Kocuria kristinae is a gram positive coccus of the family of Micrococcacae. It
      inhabits the skin and mucous membranes, but it has rarely been isolated from
      clinical specimens and is thus considered to be a non-pathogenic commensal.
      However, it may cause opportunistic infections in patients with indwelling
      devices and severe underlying diseases. We are reporting an unusual case of a
      Kocuria kristinae urinary tract infection in a catheterized, 20-years old male.
      To the best of our knowledge, this is the first reported case of a catheter
      related urinary tract infection which was caused by Kocuria kristinae. 

PMID- 24086878
TI  - A pneumococcal brain abscess: a case report.
AB  - A brain abscess which is caused by Streptococcus pneumoniae is a rare entity.
      Here, we have described a gentle man who presented with the signs and symptoms of
      a mass lesion which was localized to the temporal lobe. The clinical examination
      and computerized tomography revealed the diagnosis of a temporal abscess. The
      loculated mass was tapped and it was sent for histopathology, which confirmed the
      presence of an organizing abscess. A laboratory investigation of the pus revealed
      Streptococcus pneumoniae. The treatment included total excision and the
      administration of prolonged antibiotics, which led to a good outcome in the
      patient. 

PMID- 24086879
TI  - Meningitis due to Stenotrophomonas maltophilia after a Neurosurgical Procedure.
AB  - Stenotrophomonas maltophilia is an aerobic, glucose non- fermentative, gram
      negative bacillus, which is being increasingly recognized as a cause of serious
      infections such as bacteraemia, urinary tract infections, respiratory tract
      infections, skin and soft tissue infections, endocarditis, meningitis and ocular
      infections in hospitalized patients. The treatment of invasive S. maltophilia
      infections is difficult, as this pathogen shows high levels of intrinsic or
      acquired resistance to different antibiotics, thus reducing the options which are
      available for treatment. Meningitiscaused by S. maltophilia is rarely encountered
      and so its experience is also limited. We are describing here a case of a six
      months old, male child who developed meningitis caused by Stenotrophomonas
      maltophilia, after he underwent a neurosurgical procedure. 

PMID- 24086880
TI  - Intra-abscess administration of antibiotics through ultrasound-guided
      percutaneous catheter for the treatment of pyogenic liver abscess.
AB  - Pyogenic liver abscess is a potentially life-threatening disease. The treatment
      of a pyogenic liver abscess usually involves ultrasound guided percutaneous
      drainage because of the poor penetration of the systemic administration of
      antibiotics inside the abscess. However, a sizable proportion of patients will
      necessitate surgical interventions, which involves high peri- and post-operative
      risks. Theoretically, the local instillation of antibiotics inside the pyogenic
      liver abscess fluid could achieve a high concentration of the antibiotic for a
      long period of time. This could be especially beneficial for time-dependent
      bactericidal antibiotics such as beta-lactams, because their bactericidal
      effectiveness depends on the amount of time that bacteria are exposed to the
      antibiotic. We are reporting two patients with complicated pyogenic liver
      abscesses, who were successfully treated with systemic antibiotics and local
      instillation of meropenem inside the cavities of the abscesses. These cases
      suggest that the local instillation of the beta-lactam antibiotics could be an
      effective and a safe strategy for the treatment of pyogenic liver abscesses that
      cannot be completely drained through an ultrasound guided percutaneous catheter. 

PMID- 24086881
TI  - Chondroid choriostoma of palatine tonsil - a rare entity.
AB  - A choristoma or heterotopias is an aggregate of microscopically normal cells or
      tissues which occurs in aberrant locations. A choristoma is a tumour like mass,
      whereas heterotopias refers to a displaced tissue which is necessarily not a
      swelling or a neoplasm. We are reporting a case of a 24 year old female who
      presented with recurrent tonsillitis and halitosis. On examination, the tonsils
      were found to be enlarged. Because of the persistent symptoms, a tonsillectomy
      was performed. The histopathological examination showed features of chronic
      tonsillitis, along with presence of mature islands of hyaline cartilage which
      were surrounded by lymphoid follicles and focal areas of calcification and
      osseous metaplasia. 

PMID- 24086882
TI  - Solitary plasmacytoma of skull: a rare cytological diagnosis.
AB  - Solitary Plasmacytoma of the Skull (SPS) is very rare and only 35 cases have been
      reported in the English literature. It remains controversial whether a solitary
      plasmacytoma of the skull is essentially identical with a Solitary Plasmacytoma
      of Bone (SPB) or not. A solitary plasmacytoma of bone, which includes a solitary
      plasmacytoma of the skull, is characterized by a radiologically solitary bone
      lesion, neoplastic plasma cells in the biopsy specimen, fewer than 5% plasma
      cells in bone marrow, less than 2.0 g/dl monoclonal protein in the serum when it
      is present and a negative urine test for Bence Jones protein (monoclonal light
      chain). A solitary plasmacytoma of bone tends to disseminate or progress to
      multiple myeloma, even as long as 7-23 years after its presentation. 

PMID- 24086883
TI  - Granulocytic sarcoma presenting as an orbital mass: report of two cases.
AB  - Granulocytic sarcoma is a rare variant of a myeloid malignancy, which shows an
      extra-medullary tumour mass which is composed of myeloblasts and myeloid
      precursors with varying degrees of differentiation. It occurs most commonly in
      bone, periosteum, soft tissue, lymph nodes, and skin; although it can occur
      anywhere throughout the body. Here, we are reporting two cases of orbital
      granulocytic sarcoma in children, which presented clinically with proptosis and
      periorbital swellings, which were first diagnosed by Fine Needle Aspiration
      Cytology (FNAC). Later, peripheral blood and bone marrow aspirate examinations
      revealed the evidence of Acute Myeloid Leukaemia (AML). These cases are being
      documented to demonstrate the utility and diagnostic accuracy of FNAC in
      evaluation of this entity, in cases of unsuspected AML. Recognition of this rare
      entity is important, because giving an early aggressive chemotherapy can cause
      regression of the tumour and thus improve the patient survival. 

PMID- 24086884
TI  - Lipoma on palmar aspect of thumb: a rare case report.
AB  - Lipomas account for approximately 16% of soft tissue mesenchymal tumours. They
      are uncommon in hand and those which involve the fingers are very rare, with a
      reported incidence of 1%. In extremities, they often arise from the sub-fascial
      tissues of the hands and feet, where they may be mistaken for ganglion cysts. A
      careful dissection is necessary during the surgical procedure, in order to avoid
      recurrence. Here, we are presenting the case of an 8 years old boy who had Lipoma
      on palmar aspect of thumb. 

PMID- 24086885
TI  - Knee Locking in Osteoarthritis due to Synovial Lipoma: A Case Report.
AB  - Intra-articular synovial lipomas are very rare and only few cases have been
      reported till now. We are reporting a rare case of a unilateral intra-articular
      lipoma of osteoarthritic knee joint in a 62 years old male. Patient had two
      episodes of sudden locking of knee joint, which resolved spontaneously. A plain X
      ray showed changes which were suggestive of osteoarthritis. Clinically, patient
      was diagnosed as a case of loose bodies in left knee joint. An arthrotomy was
      performed. After a Histopathological Examination (HPE) of loose bodies, a
      diagnosis of an intra-articular synovial lipoma was made. Due to wide
      differentials and varied clinical behaviour of loose bodies, lipoma should be
      included in differential diagnosis of osteroarthritic patients who complain of
      episodic locking of knees. Intraarticular lipomas, on arthroscopic guided
      excision, get cured permanently, with no recurrence. The differentiation of an
      intra-articular lipoma from a relatively more common entity, Lipoma arborescens,
      has also been discussed. 

PMID- 24086886
TI  - Primary osteosarcoma of breast, a rare case.
AB  - Mammary sarcomas are very uncommon and make up less than 1% of all primary breast
      malignancies.Primary osteosarcoma of the breast is extremely rare and represents
      12.5% of mammary sarcomas. A secondary lesion from a primary osteosarcoma of the
      bone should be considered in the differential diagnosis. In addition, the absence
      of a direct connection between the tumour and the underlying skeleton is
      mandatory for the diagnosis.We report a case of primary osteosarcoma of the
      breast occurring in young patient with fatal evolution. 

PMID- 24086887
TI  - A Hydatid Cyst of the Appendix which Mimicked a Tubo-ovarian Mass: A Case Report
      and Review of the Literature.
AB  - Hydatid disease, an endemic in the cattle grazing areas, particularly in the
      Asian region, is a parasitic infection which is caused by the cestode tapeworm,
      Echinoccocus granulosus. There is involvement of the intra-abdominal organs apart
      from the liver, in 10-15% of the cases. We are reporting a case, wherein the
      appendix was involved with this parasitosis and we have discussed the review of
      the literature regarding the diagnostic, surgical and the newer percutaneous
      approaches for the management of this disease. 

PMID- 24086888
TI  - "Cannon balls or pus balls" in pap smears: a case report.
AB  - A 50-year old female presented with the chief complaint of a discharge per
      vaginum, which was there for the past 15 days. A routine PAP smear was received
      in the Department of Pathology, Government Medical College, Patiala, India. After
      its fixation and staining, it was examined under the microscope. It showed the
      Trichomonas vaginalis infection, with the neutrophils forming cannon balls at
      places. Neutrophils in the PAP smear are a nonspecific finding, particularly if
      they are low in numbers or if they are seen in the premenstrual and the menstrual
      phases. The neutrophils which are adherent to the squamous cells are called
      "cannon balls" or "pus balls", which are common in the Chlamydia infection. This
      case is being presented because of the presence of these rare morphological
      structures i.e. "cannon balls" or "pus balls". 

PMID- 24086889
TI  - A Caliber Persistent Artery (Dieulafoy's Lesion) which is Associated with an
      Early-Stage Gastric Stump Cancer Following a Distal Gastrectomy.
AB  - A 75-years old man was hospitalized with symptoms which suggested gastric cancer.
      Thirty-eight years ago, he had undergone a Billroth-II gastric reconstruction for
      a peptic ulcer. At the present admission, he had presented with an eight-month
      history of recurrent haematemesis, epigastric pain, vomiting, and fatigue. The
      emergent endoscopy showed a type 0-IIc (superficial depressed) early gastric
      stump cancer in the anastomotic area and total removal of the gastric remnant and
      the jejunal segment was performed. The histological examination of the surgical
      specimen showed a gastric adenocarcinoma that invaded the mucosa and the
      submucosa, without lymph node metastases (pT1bN0 stage). Besides the tumour,
      enlarged vessels were observed in the submucosa and the muscularis propria, some
      of which were thrombotic. The surrounding normal gastric wall also presented
      submucosal oversized vascular spaces, some of which were protruding through the
      muscularis mucosae in the mucosal layer. Based on these characteristics and the
      recurrent haematemesis, a final diagnosis of early gastric stump carcinoma which
      was associated with Dieulafoy's lesion was made. This association has not yet
      been reported in the literature and it allowed us to diagnose the gastric stump
      cancer in a very early stage. 

PMID- 24086890
TI  - Giant inflammatory variant of well differentiated liposarcoma: a case report of a
      rare entity.
AB  - An inflammatory liposarcoma is a rare variant of a well-differentiated
      liposarcoma. A case of a giant variety of an inflammatory well-differentiated
      liposarcoma is being reported. CT scan revealed a large abdomino-pelvic mass
      which had displaced the gut loops to left and posteriorly and urinary bladder and
      uterus to right. FNAC yielded mature adipocytes with no evidence of atypical
      cells. The large bossilated and irregular fibro-fatty mass which weighed 23 kg
      was excised. Microscopy revealed mature adipocytes with foci of fibrosis and
      abundant inflammatory cell infiltrates of eosinophils, lymphocytes, plasma cells
      and few neutrophils, along with few atypical cells. Only a few cases of a giant
      inflammatory variant of a well-differentiated liposarcoma have been reported in
      the world literature and this is first of its kind from the Indian sub-continent.
      A rare giant variant of a inflammatory well-differentiated liposarcoma with
      abundant eosinophils is being reported here, along with review of literature. 

PMID- 24086891
TI  - Holoprosencephaly with multiple anomalies of the craniofacial bones-an autopsy
      report.
AB  - Holoprosencephaly (HPE), a disorder which results from a failure of cleavage or
      the incomplete differentiation of the forebrain structures at various levels or
      to various degrees, is related to hereditary factors, chromosomal anomalies,
      cytogenetic abnormalities, and environmental teratogenic factors. We are
      reporting a case of a multiparous woman who was G3,P3,L2, who delivered a full
      term foetus with holoprosencephaly and multiple craniofacial anomalies. An
      autopsy was conducted. Multiple anomalies of the craniofacial bones, which
      include hypoplasia and synostosis of the frontal bone, anophthalmia, absence of
      the anterior cranial fossa, hypoplasia of the maxillae, an absent antrum, cleft
      palate, a central hare lip and arrhinia which includes absence of the nostrils
      and hypotelorism of the eye placodes, were noted. This case is being reported for
      its rarity and the available literature was reviewed in this respect. 

PMID- 24086892
TI  - Isolated cutaneous sarcoidosis: a new insight into the old entity.
AB  - Cutaneous lesions are a part of common manifestation in multi-systemic
      sarcoidosis and skin involvement occurs in 20% to 35% of the patients with
      systemic disease. An exclusive cutaneous involvement is rare and it is reported
      in about 4%-5% of the patients of sarcoidosis. These lesions have been classified
      into specific and non-specific, depending on the presence of non- caseating
      granulomas, on histopathologic studies. In the present study, we are reporting
      two cases of isolated cutaneous sarcoidosis without systemic manifestations,
      which is a rare presentation. Sarcoidosis will continue to challenge even the
      most experienced clinicians with respect to a high degree of suspicion and
      further investigations for diagnosing and treating this disorder. 

PMID- 24086893
TI  - The prune belly syndrome in a female foetus with urorectal septum malformation
      sequence: a case report on a rare entity with an unusual association.
AB  - The prune belly syndrome is a rare congenital anomaly which is characterized by
      the triad of an absent or a deficient development of the abdominal muscle,
      bilateral cryptorchidism and an anomalous urinary tract. In its full form, this
      condition occurs only in males. However, a similar condition occurs in females in
      the absence of cryptorchidism. On the other hand, the urorectal septum
      malformation sequence is a lethal congenital malformation which is characterized
      by the development of a phallus like structure, a smooth perineum and the absence
      of urethral, vaginal and anal openings. We are reporting a case of a female
      foetus with the prune belly syndrome, which was associated with a urorectal
      septum malformation sequence. A dead foetus with a protruded abdomen and
      ambiguous genitalia, was born at 32 weeks of pregnancy. On autopsy, it was found
      to have female internal genital organs. The left kidney, the urinary bladder and
      the rectum were absent. The sigmoid colon, the ureters and the fallopian tubes
      opened into a common cloacal sac. The histopathological examination of the ovary
      showed the presence of Leydig's cells. The occurrence of the female counterpart
      of the prune belly syndrome is extremely rare and only few of such cases were
      found to be discussed in the details in the indexed English literature so far.
      Hence, we hope that this case report will contribute to the existing knowledge on
      the prune belly syndrome. 

PMID- 24086894
TI  - Multiple hepatic inflammatory pseudotumours diagnosed after laparoscopic
      excisional biopsy.
AB  - Inflammatory pseudotumours (IPTs) may occur in almost every organ of the human
      body, the liver being the second most frequent organ which is affected.
      Inflammatory pseudotumours of the liver are rare benign lesions of unknown
      aetiology, which usually present as solitary liver masses of variable sizes. The
      differential diagnoses of malignant liver tumours are challenging and they
      usually require biopsies and histologic examinations. We are presenting the case
      of a patient with multiple hepatic lesions which mimicked liver metastases. Two
      percutaneous biopsies were inconclusive. The definitive diagnosis of multiple
      hepatic inflammatory pseudotumours was made after a laparoscopic exploration with
      an excisional biopsy of liver lesions and their pathologic evaluation. All
      lesions disappeared after several months, without any further treatments. 

PMID- 24086895
TI  - Schwannoma of the spinal accessory nerve: a case report.
AB  - We are reporting a rare case of a schwannoma which originated from the cervical
      portion of the spinal accessory nerve, which was located in the left posterior
      triangle of the neck and did not have any neurological deficit, which was
      diagnosed by the Magnetic Resonance Imaging (MRI) scan and confirmed
      histopathologically after surgery. 

PMID- 24086896
TI  - Spontaneous rupture of pyometra - a rare cause of peritonitis in elderly female.
AB  - The incidence of spontaneous perforations in pyometra is rare, being 0.01-0.5% in
      gynaecological patients. However, they are more common in postmenopausal females
      and their incidence is 13.6%. Here, we are reporting a rare case of peritonitis
      with a pneumoperitoneum in an elderly female, which was caused by a spontaneous
      perforation of pyometra. A 74-years old postmenopausal female with uncontrolled
      diabetes mellitus was admitted to surgical emergency with signs of diffuse
      peritonitis and she was in shock. After resuscitation, an emergency laparotomy
      was performed because of suspicion of a hollow viscous perforation with
      peritonitis. At laparotomy, about 2000ml of purulent fluid was found to be
      present in peritoneal cavity, while alimentary tract was intact. A rent with a
      diameter of 0.8 cm was found on fundus of uterus. A total abdominal hysterectomy
      with a bilateral salphingo oophorectomy was performed. Patient got discharged on
      12(th) post-operative day without major complications. Histopathological studies
      revealed endometritis and myometritis, with no evidence of malignancy. 

PMID- 24086897
TI  - Osteochondroma of the OsCalcaneum- A Case Report.
AB  - Osteochondromas are common benign bone tumours. They usually occur in the
      patients who are below thirty years of age. They probably are developmental
      malformations rather than true neoplasms. They are believed to originate within
      the periosteum as small cartilaginous nodules. The foot is rarely a common site
      of presentation for these tumours. The calcaneum is one of the most unusual
      regions for the occurrence of osteochondromas 1. The osteochondromas which arise
      from the calcaneum, especially those which project onto the plantar surface, pose
      considerable problem to the ambulation. Malignant transformations are seen in
      less than 1% to 2% of the patients with solitary osteochondromas 2. We herewith
      present a case of osteochondroma which arose from the calcaneum, which was
      surgically excised to improve the patient's daily functioning. The patient was
      followed up for a period of one year. She is now able to walk comfortably. 

PMID- 24086898
TI  - Aneurysmal bone cyst of the pubis: a case report.
AB  - An aneurysmal bone cyst is considered as a locally aggressive benign tumour.
      Intra-lesional extended curettage and bone-grafting is the mainstay of the
      treatment for aneurysmal bone cysts. Grafting is used usually in cases where the
      lesion compromises the mechanical strength of the bone. However, the massive size
      of the highly vascular tumour and the relative inaccessibility of its deeper
      extensions into the femoral vessels and the intra-abdominal structures,
      especially the urinary bladder, make it a relatively challenging case to perform
      excision and curettage.Presenting a case of a 15 years old male patient with the
      complaint of a right inguinal swelling since the past eight months. The swelling
      had started growing since the past two months and it was associated with pain. X
      ray showed a lytic blowout legion of the entire right pubic ramus. An intra
      lesional curettage was done. Complete tumour excision which was done by intra
      lesional curettage and biopsy yielded satisfactory results with low complications
      and low recurrence of aneurysmal bone cyst of the superior ramus of the pubis. 

PMID- 24086899
TI  - Spindle cell epithelioma: a rare vaginal tumor -a clinico pathologic report.
AB  - Spindle cell epithelioma is a very rare benign tumour of the vagina, which
      contains epithelial and mesenchymal components and co-expresses the markers for
      both. It has its origin in the epithelial cells of the remnants of the vestibular
      gland. The presence of glandular structures and the pattern of immunostaining,
      help in the differentiation of these tumours from the other common vaginal
      tumours. 

PMID- 24086900
TI  - A diagnostic dilemma: a young boy with loss of weight, pulmonary infiltrates and
      cervical lymphadenitis.
AB  - Cervical lymphadenitis is a common finding in young adults in a country like
      India, where tuberculosis is endemic. We are presenting the case of a young boy
      who presented with low grade fever, dry cough, weight loss, and a cervical
      swelling. His chest X-ray showed diffuse reticulonodular infiltrates. Contrast
      enhanced CT of chest showed bilateral multiple ring shadows. Cervical lymph node
      fine needle cytology suggested a metastatic thyroid carcinoma. He was evaluated
      extensively and a final diagnosis of a familial medullary thyroid carcinoma was
      made. Medullary thyroid carcinoma should be considered in the differential
      diagnosis of cervical lymphadenitis with lung infiltrates in young adults. It may
      be sporadic or a part of an inherited autosomal dominant disorder like multiple
      endocrine neoplasia. Genetic testing should be done for all patients with a
      diagnosis of medullary thyroid carcinoma. 

PMID- 24086901
TI  - Appendiceal Carcinoma with Krukenberg's Tumour Mimicking Primary Ovarian Cancer.
AB  - Appendiceal adenocarcinoma (AACa) is a rare tumour which represents 0.5% of all
      gastrointestinal malignancies. The prognosis is poor, because it is usually found
      at an advanced stage, that in turn, is partly due to a low threshold of suspicion
      and difficulties in diagnosis prior to surgery. It may occasionally demonstrate
      ovarian metastases that are large and which dominate the clinical and
      radiological presentations, leading to a misdiagnosis of an ovarian primary
      malignancy. We are reporting a case of an occult AACa which manifested clinically
      as a primary ovarian cancer which was at an advanced stage. Staging laparatomy
      revealed large bilateral ovarian tumours of clinical FIGO Stage III, with
      presumed appendiceal implants. Histological examination revealed a mucinous
      adenocarcinoma with a signet ring component, which involved bilateral ovaries and
      the appendix transmurally. Immunophenotypic analysis revealed a positive
      expression of CK 20 and CDX 2 and absence of CK 7 staining, which was compatible
      with appendiceal primary and ovarian metastases. The diagnosis was subsequently
      revised to AACa with Krukenberg's metastasis, Stage IV. Although AACas are
      uncommon, they should be considered in the differential diagnosis of
      intraabdominal masses and the distinction between ovarian and appendiceal primary
      malignancies is critical, as the treatment modalities vary. 

PMID- 24086902
TI  - A Non-Resolving Consolidation which was Caused by a Bronchial Foreign Body in an
      Adult: A Case Report.
AB  - A fifty year old female presented with cough, breathlessness and chest pain of
      eighteen months duration. She presented as a case of a non-resolving
      consolidation. Video bronchoscopy revealed a bronchial foreign body. This case is
      being reported here, to underline the role of bronchoscopy in a case of a non
      resolving consolidation. 

PMID- 24086903
TI  - Haemolymphangioma of epiglottis.
AB  - Lymphangiomas are congenital lesions of the lymphatic system which are most
      commonly found in the head and neck, with over 90 % of lesions manifesting in
      children who are less than 2 years of age. Haemolymphangiomas are rare variant of
      lymphangioma, with the presence of red blood cells within the lymphatic channels.
      Laryngeal sites are usually in continuity with foci of disease in the neck. In
      general, symptoms are non-specific and they vary with the site and size of the
      mass. Usually, they occur before 2 years of age. Isolated cases of lymphangiomas
      with involvement of epiglottis are rare and only a few cases have been reported
      so far. We are reporting the case of a six-year-old girl who presented with a
      mass in the epiglottis. 

PMID- 24086904
TI  - Management of giant cystic lymphangioma in an infant.
AB  - Lymphangiomas are benign lesions with a marked predilection for the head and neck
      region. Giant lymphangiomas of head and neck may occur and they may present with
      life threatening complications. The author is presenting here, a three month-old
      boy who presented with a giant cystic lymphangioma on left side of neck, which
      extended to the head as well. His clinical diagnosis of a cystic lymphangioma was
      confirmed on a Ultrasonography (USG) examination. Complete surgical excision of
      the lesion was achieved, without damaging any vital structures. His post
      operative recovery was uneventful. A follow-up at two months after his surgery
      showed a cosmetically acceptable scar and no recurrence was noted. 

PMID- 24086905
TI  - Parameatal cyst: a presentation of rare case and review of literature.
AB  - A parameatal urethral cyst is a very rare congenital anomaly. It was first
      reported in two males in 1956 by Thompson and Lantin. About 50 cases have been
      published since then. Most of the cases which have been reported were from
      Japanese population and on extensive literature search, few cases were found to
      have been reported from India. We are reporting a case of a parameatal urethral
      cyst in a 7-year-old boy. Complete excision of the cyst with total removal of the
      epithelium is required for treatment and for prevention of recurrence. 

PMID- 24086906
TI  - Infantile or malignant osteopetrosis: case report of two siblings.
AB  - Infantile or Malignant osteopetrosis is a rare congenital disorder of bone
      resorption. It is caused by failure of osteoclasts to reabsorb immature bone.
      Severe infantile or malignant osteopetrosis present at birth or develops within
      the first few months of life. We are reporting here a case of two siblings with
      malignant osteopetrosis. Prominent clinical features included marked pallor,
      noisy respiration, progressive blindness and developmental delay. 

PMID- 24086907
TI  - Asymptomatic disseminated cysticercosis.
AB  - Cysticercosis is a common problem world wide. However, disseminated cysticercosis
      is rare. Still rarer is asymptomatic disseminated cysticercosis. We are reporting
      here a rare case of asymptomatic disseminated cysticercosis which involved brain,
      face, orbit, lungs, heart, pancreas and spleen in a young Nigerian male, who
      sought medical attention for dysphagia which was diagnosed as achalasia cardia.
      Despite widespread dissemination of cysticercosis which involves multiple organs,
      the individual was asymptomatic for the same. Pancreatic and splenic involvement
      in disseminated cysticercosis has extremely rarely been reported in literature. 

PMID- 24086908
TI  - Effect of Physical activity on Insulin Resistance, Inflammation and Oxidative
      Stress in Diabetes Mellitus.
AB  - Diabetes Mellitus is a growing health concern projected to affect 366 million
      people worldwide by around 2030. Multiple approaches to address this health
      concern are documented; amongst which increased the habitual physical activity
      has been shown to be beneficial. Various mechanisms demonstrated show improvement
      of cellular insulin sensitivity. The interplay between insulin sensitivity and
      insulin resistance plays a key role in development and persistence of the
      diabetic state, which can be directly linked to the levels of physical activity.
      Regulation of adiponectin and leptin levels are also linked to physical activity
      via reduction of central obesity. Inflammatory markers, free radical reduction
      and up-regulation of physiological antioxidant processes are also observed in
      subjects with increased physical activity schedules, all of which play a
      significant role in the pathogenesis of Diabetes Mellitus. 

PMID- 24086909
TI  - Hepcidin-minireview.
AB  - Iron related disorders are encountered in daily clinical settings. Maintenance of
      stable extracellular iron concentrations requires the coordinate regulation of
      iron transport into plasma from dietary sources in the duodenum, from recycled
      senescent red cells in macrophages and from storage in hepatocytes. Hepcidin acts
      as a systemic iron-regulatory hormone. Many human diseases are associated with
      alterations in hepcidin concentrations. This review has focused on hepcidin
      structure, kinetics and function, its correlation with iron metabolism disorders,
      the therapeutic potential for modulating hepcidin expression and the diagnostic
      potential of hepcidin measurements in clinical practice. 

PMID- 24086910
TI  - Digital Evaluation of Functional Occlusion Parameters and their Association with
      Temporomandibular Disorders.
AB  - CONTEXT: Dental researchers are contradictory in their opinion on the role of
      occlusion in TMD. Occlusal evaluation of both conventional and digital methods in
      TMD patients will provide the accurate information about the factors accountable
      for occlusal instability. Identifying the factors responsible will facilitate
      precise diagnosis and treatment for TMD. AIM: The AIM of the study was to
      determine the dynamic occlusal parameters strongly associated with the etiology
      of Temporomandibular disorders. MATERIAL AND METHODS: Study group consisted of
      100 patients; it included 50 patients with normal TMJ(Group I) and remaining 50
      patients had a minimum of one positive sign or symptom of Temporomandibular
      disorder (GroupII). The patient's dynamic occlusal contacts were evaluated by
      both conventional and digital methods. The Articulating paper was utilized for
      conventional occlusion analysis. During conventional analysis centric, lateral
      and protrusive interferences were evaluated along with loss of vertical
      dimension. Digital occlusal analysis was performed with T-Scan III. Clusion time,
      disclusion times were recorded for both groups. Chi-square and Student't'
      statistical analyses were performed to ascertain the association and
      statistically significant difference between the groups using SPSS19. RESULTS:
      Group II patients predominantly (66%)had Group-function occlusion compared to
      Group I subject. Centric slide more than 2 mm found to have strong influence (p
      value 0.008) on the etiology of TMD. Among the occlusal interferences evaluated
      balanced side interferences had a strong correlation with TMD with p-value of
      0.003. Working side interferences, protrusive interferences had a p-value of
      0.157, 0.826 respectively, indicating weak association. T-Scan analysis showed
      Group I had 0.689, 0.9136, 0.7952, 0.9794 seconds of clusion, left, right,
      protrusive disclusion time respectively compared to corresponding 1.862, 1.7995,
      1.6978, 1.9296 seconds for Group II. Statistically significant difference
      (p<=0.05) was found between the mean values of both groups. CONCLUSION: Among the
      dynamic occlusal parameters evaluated centric slide and balancing side
      interferences were found to be highly influential in TMD etiology. TMD patients
      had prolonged clusion and disclusion times compared to healthy TMJ patients.

PMID- 24086911
TI  - Evaluation of Periodontitis as a Risk for Preterm Birth among Preeclamptic and
      Non-Preeclamptic Pregnant Women - A Case Control Study.
AB  - BACKGROUND: Periodontal disease during pregnancy markedly increases the woman's
      risk of developing preeclampsia. The aim of the present study was to evaluate and
      compare whether periodontal disease increases the risk of preterm birth among
      preeclamptic and non-preeclamptic pregnant women. METHODS: A total of 200
      pregnant women (100 preeclamptic and 100 non-preeclamptic) with periodontitis
      aged 20 to 30 years & < to 26(th) week of gestation. Maternal demographic and
      medical data was collected from concerned institutes. In both groups, blood
      pressure of more than 140/80 mm Hg, presence of protein in 24 hours urine, of
      more than 1gm per litre in 2 or more mid stream specimens obtained 6 hours apart
      in the absence urinary tract infection, confirmed by 0.3 g per 24 hours of urine
      specimens and ankle edema were measured. The periodontal status was categorised
      as healthy, mild, moderate/severe our worsening. Probing depth (PD), attachment
      levels and bleeding on probing were measured with UNC-15 probe at six sites per
      tooth. All the periodontal parameters were measured at second prenatal visit and
      within 48 hours post-partum. RESULTS: The present study revealed; the Incidence
      of preterm birth in relation to periodontal status in preeclamptic patients was
      significantly high (p<0.001). Total incidence of preterm birth in relation to
      periodontal status in preeclamptic and non-preeclamptic had chi-square value of
      17.7, which is highly significant (p< 0.001). CONCLUSION: The present study
      demonstrated that pregnant women with preeclampsia are at greater risk for
      preterm delivery if periodontal disease is present during pregnancy or progress
      during pregnancy and also rate of preterm delivery is more in preeclamptic women
      having moderate to severe periodontal disease.

PMID- 24086912
TI  - Biometric Analysis - A Reliable Indicator for Diagnosing Taurodontism using
      Panoramic Radiographs.
AB  - BACKGROUND: Taurodontism is a clinical entity with a morpho-anatomical change in
      the shape of the tooth, which was thought to be absent in modern man.
      Taurodontism is mostly observed as an isolated trait or a component of a
      syndrome. Various techniques have been devised to diagnose taurodontism. AIM: The
      aim of this study was to analyze whether a biometric analysis was useful in
      diagnosing taurodontism, in radiographs which appeared to be normal on cursory
      observations. SETTING AND DESIGN: This study was carried out in our institution
      by using radiographs which were taken for routine procedures. MATERIAL AND
      METHODS: In this retrospective study, panoramic radiographs were obtained from
      dental records of children who were aged between 9-14 years, who did not have any
      abnormality on cursory observations. Biometric analyses were carried out on
      permanent mandibular first molar(s) by using a novel biometric method. The values
      were tabulated and analysed. STATISTICS: Fischer exact probability test, Chi
      square test and Chi-square test with Yates correction were used for statistical
      analysis of the data. RESULTS: Cursory observation did not yield us any case of
      taurodontism. In contrast, the biometric analysis yielded us a statistically
      significant number of cases of taurodontism. However, there was no statistically
      significant difference in the number of cases with taurodontism, which was
      obtained between the genders and the age group which was considered. CONCLUSION:
      Thus, taurodontism was diagnosed on a biometric analysis, which was otherwise
      missed on a cursory observation. It is therefore necessary from the clinical
      point of view, to diagnose even the mildest form of taurodontism by using metric
      analysis rather than just relying on a visual radiographic assessment, as its
      occurrence has many clinical implications and a diagnostic importance.

PMID- 24086913
TI  - The oral health status and the treatment needs of salt workers at sambhar lake,
      jaipur, India.
AB  - BACKGROUND: Salt workers are exposed to the adversities of environmental
      conditions such as direct sunlight, salt dust and contact with brine, which have
      an impact on the health of workers. Since oral health is an integral part of the
      general health, we planned to determine its effect on the oral cavity.
      OBJECTIVES: To assess the oral health status and the treatment needs among the
      workers of Sambhar Salts Limited at Sambhar Lake, Jaipur, India. MATERIAL AND
      METHODS: A cross sectional, descriptive survey was conducted among 979 subjects
      (509 males; 470 females) who were aged between 19-68 years, who were the workers
      of Sambhar Salts Limited, Sambhar Lake, Jaipur, India. An interview on the
      demographic profile followed a clinical examination for recording the oral health
      status, based on the World Health Organization guidelines. The Chi-square test, t
      test, One way Analysis of Variance and a Stepwise multiple linear regression
      analysis were used for the statistical analysis. RESULTS: Females had a
      significantly greater prevalence of dental fluorosis (71.7%) and periodontal
      disease (96.4%) as compared to males (p= 0.001). The mean number of healthy
      sextants (0.71 +/- 0.09) and the mean DMFT (5.19 +/- 4.11) were also
      significantly higher in females as compared to those in males (p=0.001). One
      surface filling (78.2%), followed by pulp care and restoration (76.1%) were the
      most prevalent treatment needs. The gender and oral hygiene practices for dental
      caries and periodontal disease were respectively identified as the best
      predictors. CONCLUSION: Considerable percentages of salt workers have
      demonstrated a higher prevalence of oral diseases. Higher unmet treatment needs
      suggest a poor accessibility and availability of oral health care, in addition to
      a low utilization of preventive or therapeutic oral health services.

PMID- 24086914
TI  - Laser gingival retraction: a quantitative assessment.
AB  - BACKGROUND: Proper gingival retraction improves the prognosis of crowns and
      bridges with sub gingival finishlines.Use of lasers assists the operator to
      achieve proper retraction with good clinical results. AIMS: The present study was
      intended to assess the amount of lateral gingival retraction achieved
      quantitatively by using diode lasers. SETTINGS AND DESIGN: Study was carried on
      20 patients attended to a dental institution that underwent root canal treatment
      and indicated for fabrication of crowns. MATERIAL AND METHODS: Gingival
      retraction was carried out on 20 teeth and elastomeric impressions were obtained.
      Models retrieved from the impressions were sectioned and the lateral distance
      between finish line and the marginal gingival was measured using tool makers
      microscope. Retraction was measured in mid buccal, mesio buccal and disto buccal
      regions. STATISTICAL ANALYSIS: The values obtained were used to calculate the
      mean lateral retraction in microns. RESULTS: Mean retraction values of 399.5 MUm,
      445.5 MUm and 422.5MUm were obtained in mid buccal, mesio buccal and disto buccal
      regions respectively. CONCLUSIONS: Gingival Retraction achieved was closer to the
      thickness of sulcular epithelium and greater than the minimum required retraction
      of 200um.

PMID- 24086915
TI  - Prevalence, severity and associated factors of dental caries in 3-6 year old
      children.
AB  - OBJECTIVES: To determine the prevalence and the severity of dental caries in 3-6
      year old children in Chennai and to elucidate the factors which affect the dental
      caries in 3-6 year old children. METHODS: This study was a cross-sectional survey
      which was done on 527 children who were in the age group of 3 to 6 years, who
      were from 6 private and 6 corporation schools in Chennai, India. Two instruments
      were developed, pre-tested and validated for the study. One questionnaire which
      contained the various risk factors which had to be measured and the dental caries
      indices were used on children to collect the relevant data. A separate
      questionnaire was distributed to the parents to measure the socio economic status
      and to know the parents' educational levels. RESULTS: The prevalence of dental
      caries was found to be 63.4% in the study samples. The association between dental
      caries and the associated factors was determined by calculating the Odd's ratio.
      Logistic regression was performed to test the magnitude of the association
      between dental caries and the factors which were associated with it, and linear
      regression was done for the continuous variables. There was a statistically
      significant high association between the oral hygiene practice, the eating habits
      of the children, the economic status and the parents' literacy levels and the
      caries prevalence in this study. CONCLUSION: This study showed that preventive
      efforts should be focused on young children, as the benefits are cumulative. The
      oral health promotion should particularly be targeted to the areas of need, to
      redress the inequalities.

PMID- 24086916
TI  - A Subjective Assessment of Perceived Clarity of Indirect Digital Images and
      Processed Digital Images with Conventional Intra-oral Periapical Radiographs.
AB  - OBJECTIVES: To compare and analyze the perceived clarity and diagnostic value of
      Conventional periapical Radiographs (CRs) with those of their Digitized
      Periapical Images (DIs) and Processed Digitized Periapical Images (PDIs)
      counterparts. MATERIAL AND METHODS: Forty two intraoral periapical radiographs of
      patients with clinically suspected periapical pathosis were made to constitute
      the group of CRs. These were photographed by using a Canon Power Shot SD500 (7.1
      Megapixel) digital camera and the unaltered images were transferred to a computer
      laptop, to form the group of DIs. Subsequently, the contrast and brightness of
      these images were modified to represent the group of PDIs. Two experienced oral
      radiologists independently evaluated 5 specific apical and periapical region
      parameters of all the 42 CRs, DIs and PDIs for perceived image quality and
      diagnostic value and graded them on a three point grading scale. Conventional
      radiographs served as the control. Data were analyzed by using paired t-test and
      Kappa analysis. RESULTS: The clarity and diagnostic quality of the PDIs were
      statistically significant as compared to those of their conventional
      counterparts. In comparison, the DIs group fared badly, with deterioration of the
      image quality. The interobserver agreement was good and all the results were
      statistically significant. CONCLUSION: Indirectly digitizing the radiographs by
      employing a digital camera and further digitally processing the images resulted
      in an improvement in their perceived clarity and they enhanced their diagnostic
      properties.

PMID- 24086917
TI  - The Effect of Al2O3 Addition on the Thermal Diffusivity of Heat Activated Acrylic
      Resin.
AB  - AIM: This study aimed at investigating the effect of adding 5% to 20% by weight
      aluminium oxide powder (Al2O3) on thermal diffusivity of heat-polymerized acrylic
      resin. MATERIAL AND METHODS: Twenty five cylindrical test specimens with an
      embedded thermocouple were used to determine thermal diffusivity over a
      physiologic temperature range (0 to 70 degrees C). The specimens were divided
      into five groups (5 specimens/group) which were coded A to E. Group A was the
      control group (unmodified acrylic resin specimens). The specimens of the
      remaining four groups were reinforced with 5%, 10%, 15%, and 20% Al2O3 by weight.
      RESULTS were analysed by using one-way analysis of variance (ANOVA). RESULTS:
      Test specimens which belonged to Group E showed the highest mean thermal
      diffusivity value of 10.7mm(2)/sec, followed by D (9.09mm(2)/sec), C
      (8.49mm(2)/sec), B(8.28mm(2)/sec) and A(6.48mm(2)/sec) groups respectively.
      Thermal diffusivities of the reinforced acrylic resins were found to be
      significantly higher than that of the unmodified acrylic resin. Thermal
      diffusivity was found to increase in proportion to the weight percentage of
      alumina filler. CONCLUSION: Al2O3 fillers have potential to provide increased
      thermal diffusivity. Increasing the heat transfer characteristics of the acrylic
      resin base material could lead to more patient satisfaction.

PMID- 24086918
TI  - Verruciform xanthoma of the oral cavity - a case report.
AB  - Verruciform Xanthoma (VX) is a relatively rare benign mucocutaneous lesion of
      unknown aetiology. VX occurs predominantly in oral cavity which also occasionally
      affects skin and genital mucosa. It was first reported in the oral cavity in
      1971. This rare harmless lesion usually presents as sessile or pedunculated,
      appear as a papule or single plaque showing verrucous or papillomatous mucosal
      growth with variable color from reddish pink to gray. In majority of oral cases,
      it affects gingiva and alveolar mucosa that may be mistaken for benign,
      premalignant and malignant conditions. VX is diagnosed with certainly only on
      histopathologic examination. Histologically VX is characterized by the presence
      of parakeratinized epithelium showing papillary or verrucous growth with thin
      rete ridges and connective tissue papillae extending up to the surface. The
      papillae characteristically consist of foam cells also called xanthoma cells.
      Here we describe a case report of verruciform xanthoma occurring on the buccal
      mucosa in a 42-years old male patient along with its clinical, pathogenesis,
      histological features and treatment modalities discussed. 

PMID- 24086919
TI  - Multiple mandibular exostoses: a rare case report.
AB  - Multiple maxillary and mandibular exostoses are common localized overgrowths of
      the bone. They are non-neoplastic and are thought to be reactive or developmental
      in origin. These exostoses need to be accurately distinguished from the other
      more diagnostically significant lesions, notably from the exosteal osteomas. The
      aetiology of exostosis has been investigated by different authors, but no
      consensus has been reached so far. We are reporting a rare case of an otherwise
      healthy 38 year old female with multiple exostoses in the mandibular anterior
      region, which correlated both clinically and radiographically. 

PMID- 24086920
TI  - Fibrosarcoma of the mandible: a diagnostic dilemma.
AB  - Fibrosarcoma is a malignant mesenchymal neoplasm of fibroblasts that rarely
      affects oral cavity and can cause local recurrences or metastasis. The aetiologic
      factors are still unknown, but many authors have reported the radiation therapy
      history as an important aetiological factor, followed by trauma and underlying
      conditions like Paget's disease, fibrous dysplasia or chronic osteomyelitis.
      Fibrosarcoma of mandible is rare, with an incidence which ranges from 0-6.1% of
      all primary fibrosarcomas of the bone. This paper has described a case of a
      swelling in the mandible of a 17-years old female who had a radiolucency in
      association with crown of an impacted tooth and foci of radiopacity, which led to
      a misdiagnosis of either an odontogenic lesion or a bone tumour, but proved to be
      a fibrosarcoma on histopathological and immunohistochemistry investigations. 

PMID- 24086921
TI  - A variation in tooth position-180 degrees  rotated maxillary second premolar.
AB  - Rotation of a tooth around an axis which is perpendicular to the occlusal plane
      through angles which approach 180 degrees  is a rare anomaly which is found in
      the human dentition. Such aberrations present a multi-factorial model in their
      origin. Both genetic and local factors seem to contribute to this abnormality. If
      the contribution of local factors could be identified, a way could open to an
      early treatment and prevention of secondary rotations of opposing and contiguous
      teeth. A case of a 180 degrees  rotation of maxillary left second premolar in a
      male patient of Indian origin has been described here. 

PMID- 24086922
TI  - Dentinogenesis Imperfecta : A Family which was Affected for Over Three
      Generations.
AB  - Dentinogenesis Imperfecta (DI) or hereditary opalescent dentin is inherited in a
      simple autosomal dominant mode with high penetrance and low mutation rates. It
      generally affects both the deciduous and the permanent dentitions. DI corresponds
      to a localized form of mesodermal dysplasia which is observed in the histo
      differentiation. An early diagnosis and treatment are therefore fundamental,
      which aim at obtaining a favourable prognosis, since at late intervention makes
      the treatment more complex. We are presenting here a case of DI in which the
      disease affected the three generations of a family in India. 

PMID- 24086923
TI  - Non-syndromic bilateral supplemental maxillary lateral incisors: a rare case.
AB  - Supernumerary teeth or hyperdontia are defined as the teeth that exceeds the
      normal dental formula, regardless of their location and morphology. A
      supernumerary tooth is a developmental anomaly and it has been argued to arise
      from multiple aetiologies. Supernumerary teeth with orthodox shapes and sizes,
      that resemble the normal dentition are called 'supplemental teeth'. The
      supplemental teeth are often overlooked because of their normal shapes and sizes.
      Supplemental lateral incisors are rare and bilateral cases are even rarer, with
      only two cases being reported in the literature till date. Therefore, we are
      describing a rare case of non-syndromic, bilateral, supplemental, maxillary,
      lateral incisors and we have discussed the management of supernumerary teeth. 

PMID- 24086924
TI  - C Spine Fracture on OPG.
AB  - Maxillofacial injuries are common and they occur in a variety of situations. All
      patients who undergo maxillofacial or head trauma, are presumed to sustain
      cervical spine injuries. Identification of cervical spine injuries is essential
      in management of trauma, because a missed injury can result in a catastrophic
      spinal cord injury. Advanced Trauma Life Support (ATLS) guidelines have suggested
      that routine use of cervical spine radiographs may not be required in an
      asymptomatic patient. We are presenting here a case with a cervical spine injury
      with no clinical deficits, found incidentally on panoramic radiographs which were
      advised for evaluation of the mandibular fracture. We suggest that importance has
      to be given to examination of the cervical spine on the panoramic radiographs as
      well. 

PMID- 24086925
TI  - Radicular cyst with severe destruction of the buccal cortical plate secondary to
      endodontic failure.
AB  - This case report highlights a massive radicular cyst with respect to the lower
      left premolars, that developed secondary to endodontic failure and resulted in
      buccal cortical bone destruction. It also discusses the investigation and the
      surgical approach which were carried out with regard to the cyst. Following
      surgical closure, the teeth were endodontically retreated. It also highlights the
      fact that mandibular true occlusal radiographs could be misleading with regard to
      the extent of bone destruction, which can otherwise be confirmed on CT scans. 

PMID- 24086926
TI  - Natural teeth replacing artificial teeth in a partial denture: a case report.
AB  - The aesthetic replacement of anterior teeth in cases of immediate partial denture
      is always a challenging work for prosthodontists. There is always problem of
      matching size, colour, shade and shape of the replaced tooth with those of the
      natural teeth. It was most difficult to satisfy the patients who have high
      aesthetic demands. Here is a report of a case where patient's own natural tooth
      was used for replacement in an immediate partial denture. An immediate denture is
      defined as "any removable dental prosthesis which is fabricated for placement
      immediately, following the removal of a natural tooth/teeth" . Patients with
      missing anterior teeth lack an impressive appearance aesthetically and as well as
      psychologically. Tooth loss leads to a certain degree of loss of function. This
      loss of function might lead to an impairment of oral health which is related to
      quality of life. An immediate denture can replace 1-16 teeth in either the
      maxillary or the mandibular arch, or in both arches. The need for the immediate
      replacement of a missing tooth is more in case of an anterior tooth, where
      aesthetics is of prime concern. The replacement of an anterior tooth is most
      technique sensitive, as it includes the patient's expectations, which include,
      matching with proper shade, shape and size as those of his/her natural teeth. So,
      here is a case presentation where modern day patient expectations were taken into
      consideration. 

PMID- 24086927
TI  - Teriparatide: a novel means to ultimately achieve true regeneration!!!
AB  - "Perioceutics" or the use of the pharmacological agents which are specifically
      developed to manage periodontitis, is an interesting and an emerging aid in the
      management of periodontal diseases, along with mechanical debridement. Host
      modulation therapies are being proposed and developed to bring down excessive
      levels of enzymes, cytokines, prostanoids, as well modulate osteoclast functions.
      Over the past two decades, many drugs have been investigated for their host
      modulating properties in both animal and early human clinical studies. These
      agents include non-steroidal anti-inflammatory drugs, sub antimicrobial dose
      doxycycline and systemic bisphosphonates. Recently, a new drug has been added to
      the list, namely, teriparatide, which is a bone forming drug. It is a
      biosynthetic human parathyroid hormone. Multiple clinical trials have shown that
      teriparatide is associated with increased bone mineral density. This review has
      focused on the mechanism of action of teriparatide and its potential role in the
      treatment of periodontal disease. 

PMID- 24086928
TI  - Early Detection of Oral Squamous Cell Carcinoma (OSCC) - Role of Genetics: A
      Literature Review.

PMID- 24086929
TI  - Emerging trends of herbal care in dentistry.
AB  - Herbs are staging a comeback and herbal 'renaissance' is happening all over the
      globe. The herbal products, today, symbolize safety, in contrast to the
      synthetics that are regarded as unsafe to humans and the environment. A herb,
      botanically speaking, is any plant that lacks the woody tissue which is
      characteristic of shrubs or trees. More specifically, herbs are plants which are
      used medicinally or for their flavour or scent. Herbs with medicinal properties
      are a useful and an effective source of treatment for various disease processes.
      Herbal extracts have been successfully used in dentistry as tooth cleaning and
      antimicrobial plaque agents. The use of herbal medicines continues to expand
      rapidly across the world. Many people take herbal medicines or herbal products
      now for their health care in different national healthcare settings. Herbal
      extracts have been used in dentistry for reducing inflammation, as antimicrobial
      plaque agents, for preventing release of histamine and as antiseptics,
      antioxidants, antimicrobials, antifungals, antibacterials, antivirals and
      analgesics. They also aid in healing and are effective in controlling microbial
      plaque in gingivitis and periodontitis, thereby improving immunity. 

PMID- 24086930
TI  - The red cell distribution width may be affected by many factors in the clinical
      practice.

PMID- 24086931
TI  - A Study on the AmpC Production Amongst the Urinary Enterobacteriaceae Isolates.

PMID- 24086932
TI  - Fighting back against chronic myelomonocytic leukemia.

PMID- 24086933
TI  - Surviving in the era of "Big Data".

PMID- 24086934
TI  - Multiple myeloma with spindle-like cell morphology.

PMID- 24086935
TI  - Solitary pulmonary plasmacytoma.

PMID- 24086936
TI  - Review of the clinical research conducted by the Consortium for Improving
      Survival of Lymphoma of the Korean Society of Hematology Lymphoma Working Party.
AB  - The Consortium for Improving Survival of Lymphoma (CISL) in Korean Society of
      Hematology Lymphoma Working Party had first meeting in February, 2006 with 10
      institutions and 12 members. Now CISL comprised of 64 centers. CISL has
      concentrated research activity on lymphomas which are relatively frequent in
      Korea and has tried to give favors for the Korean lymphoma patients. CISL has
      conducted more than 30 retrospective studies to evaluate Korean peculiar lymphoma
      subtypes. More than 30 prospective trials have been being performed for diffuse
      large B-cell lymphoma, marginal zone lymphoma, extra-nodal NK/T-cell lymphoma,
      and so on. The first prospective trial for advanced marginal zone lymphoma has
      led to use Rituximab containing chemotherapy with the re-imbursement of health
      insurance in Korea. The multi-center trials of the CISL with new therapeutic
      modalities will improve further the survival of lymphoma patients not only
      quantitatively but also qualitatively. 

PMID- 24086937
TI  - Allogeneic hematopoietic cell transplantation in adult patients with
      myelodysplastic/myeloproliferative neoplasms.
AB  - BACKGROUND: In adults, the 2 main types of myelodysplastic/myeloproliferative
      neoplasms (MDS/MPN) are chronic myelomonocytic leukemia (CMML) and atypical
      chronic myeloid leukemia (aCML). Both are associated with a poor prognosis.
      Allogeneic hematopoietic cell transplantation (HCT) is the only known curative
      treatment modality for these diseases, but data on outcomes following such
      treatment are limited. We analyzed the outcomes of patients with MDS/MPN after
      allogeneic HCT. METHODS: This retrospective study included 10 patients with
      MDS/MPN who received allogeneic HCT at Asan Medical Center from 2002 to 2010. Of
      these 10 patients, 7 had CMML, 2 had aCML, and 1 had unclassifiable MDS/MPN. Five
      patients received a myeloablative conditioning (MAC) regimen (busulfan
      cyclophosphamide), and 5 received reduced-intensity conditioning (RIC) regimen.
      RESULTS: Neutrophil engraftment was achieved in all patients. After a median
      follow-up of 47.5 months among surviving patients, 4 had relapsed and 5 had died.
      There was only 1 treatment-related death. The 5-year rates of overall, relapse
      free, and event-free survival were 42.2%, 51.9%, and 46.7%, respectively. Relapse
      was the leading cause of treatment failure, and all relapses were observed in
      patients who had received RIC and who did not develop chronic graft-versus-host
      disease. CONCLUSION: Allogeneic HCT can induce durable remission in patients with
      MDS/MPN, but RIC cannot replace MAC in patients eligible for myeloablative
      treatments.

PMID- 24086938
TI  - Evaluation of prognostic factors in patients with therapy-related acute myeloid
      leukemia.
AB  - BACKGROUND: Therapy-related AML (t-AML) occurs as a late complication of
      chemotherapy administered to treat a prior disorder. Prognostic factors affecting
      the clinical outcome in t-AML have not yet been clearly defined; therefore, we
      evaluated these factors in this study. METHODS: Forty-eight patients diagnosed
      with t-AML within the past 10 years were enrolled, and their chemotherapy
      regimens categorized into 4 groups: alkylating agents (AK) only, topoisomerase II
      inhibitors (TI) and AK, TI only, and others. The prognostic factors affecting
      clinical outcome were evaluated. RESULTS: Five (10.4%), 21 (43.8%), 9 (18.8%),
      and 13 (27.0%) patients were treated with AK only, AK and TI, TI only, and
      others, respectively. Patients with an AML M3 phenotype showed significantly
      longer overall survival (OS; 55.1 vs. 14.3 months, P=0.040) and disease-free
      survival (DFS; 61.2 vs. 17.5 months, P=0.049) than other phenotypes. In contrast,
      patients with a complex karyotype showed significantly shorter OS (7.9 vs. 31.3
      months, P=0.008) and DFS (9.5 vs. 38.6 months, P=0.046); additionally, patients
      with chromosome 5 or 7 abnormalities showed significantly shorter OS (9.1 vs.
      30.7 months, P=0.011) than other phenotypes. Only the presence of a complex
      karyotype or AML M3 phenotype retained prognostic impact in a multivariate
      analysis. CONCLUSION: Only the AML M3 phenotype was identified as having a good
      prognosis, and this might suggest that it exhibits unique clinical features in t
      AML patients. Moreover, our findings indicated that karyotype was the strongest
      prognostic indicator and predicted a poor prognosis for t-AML patients with a
      complex karyotype.

PMID- 24086939
TI  - Mean cell volumes of neutrophils and monocytes are promising markers of sepsis in
      elderly patients.
AB  - BACKGROUND: Sepsis in elderly patients is a major cause of morbidity and
      mortality in the clinical setting. The aim of this study was to assess the
      diagnostic significance of volume conductivity scatter (VCS) parameters and to
      compare their reliability with that of inflammatory markers. METHODS: Patients
      (N=85) were divided into 3 groups according to their clinical history and culture
      results: control (N=29), localized infection (N=38), and sepsis (N=18). VCS
      parameters were obtained using a UniCel DxH 800 Coulter system. Cut-off values
      were established based on receiver operator characteristic (ROC) curves. RESULTS:
      The mean volumes of neutrophils (MNV) and monocytes (MMV) were higher in the
      sepsis group than in the localized infection and control groups (P=0.000 for
      both). The mean cell conductivity and low median angle light scatter of
      neutrophils were lower in the sepsis group than in the localized infection and
      control groups (P=0.029 and P=0.022, respectively). With a cut-off of 156.5, MNV
      had a sensitivity of 83.3% and a specificity of 78% in predicting sepsis.
      CONCLUSION: MNV and MMV, which can be obtained easily using an automated blood
      analyzer, may be promising hematologic parameters for distinguishing elderly
      individuals with and without sepsis and may help clinicians in the diagnosis of
      sepsis.

PMID- 24086940
TI  - The impact of novel therapeutic agents before and after frontline autologous stem
      cell transplantation in patients with multiple myeloma.
AB  - BACKGROUND: Novel agents (NAs) such as thalidomide and bortezomib have been
      administered in combination with autologous stem-cell transplantation (ASCT) to
      effectively treat multiple myeloma (MM). However, whether NAs perform better as
      induction treatments prior to transplantation, or as post-transplant maintenance
      therapies remains unclear. METHODS: We retrospectively analyzed 106 consecutive
      patients with MM who underwent ASCT within 1 year of diagnosis as first-line
      therapy. RESULTS: Eighty-seven (82.1%) patients received NAs before ASCT, whereas
      68 (64.2%) received NAs after ASCT. NAs were administered to each patient as
      follows: before ASCT alone (N=29, 27.4%), after ASCT alone (N=10, 9.4%) or both
      before and after ASCT (N=58, 54.7%). High-quality rates before and after ASCT
      were significantly higher for patients who received NAs as induction treatment
      compared to those who did not receive pre-transplant NAs. At a median follow-up
      of 37.9 months, the 3-year progression-free survival (PFS) and overall survival
      (OS) rates were 42.8% and 70.2%, respectively. The PFS and OS were significantly
      higher in patients with NAs as post-transplant maintenance treatment (P=0.03 and
      P=0.04, respectively), but not in those with NAs as pre-transplant induction
      treatment. The PFS of patients with NAs before and after ASCT was higher than
      that of the patients with NAs as induction therapy alone (P=0.05). Age, serum
      beta2-microglobulin level, complete response after ASCT, and NA use post-ASCT
      independently predicted survival outcomes. CONCLUSION: These findings suggest
      that integration of NAs post-ASCT could benefit patients with MM undergoing ASCT.
      Induction therapy using NAs also improves high-quality response rates before and
      after ASCT.

PMID- 24086941
TI  - Sequence variation data of F8 and F9 genes in functionally validated control
      individuals: implications on the molecular diagnosis of hemophilia.
AB  - BACKGROUND: The F8 and F9 genes encode for coagulation factor VIII (FVIII) and
      FIX, respectively, and mutations in these genes are the genetic basis of
      hemophilia A/B. To determine whether a sequence variation in F8/F9 is a disease
      causing mutation, frequency data from a control population is needed. This study
      aimed to obtain data on sequence variation in F8/F9 in a set of functionally
      validated control chromosomes of Korean descent. METHODS: We re-sequenced F8 and
      F9 from DNA samples of 100 Korean male control individuals with normal PT, aPTT,
      and FVIII activity. PCR and direct sequencing analyses were performed using
      primer pairs to cover all coding regions and the flanking intronic sequences.
      RESULTS: Thirteen individuals (13%) were hemizygous for sequence variations in
      the coding region of F8. Six (6%) had c.3780C>G (p.Asp1260Glu), five (5%) had
      c.3864A>C (p.Ser1288=). One each individual (1%) had c.4794G>T (p.Glu1598Asp) and
      c.5069 A>G (p.Glu1690Gly). Asp1260Glu and Ser1288= were known SNPs (rs1800291 and
      rs1800292, respectively). Glu1598Asp was assigned as a missense mutation in
      public databases (HGMD and HAMSTeRS), and Glu1690Gly was a novel variation. Based
      on the normal FVIII activities in control individuals carrying these variations
      (109% and 148%, respectively), they were considered to be rare SNPs. No variation
      was observed in F9 of control individuals. CONCLUSION: A significant proportion
      of control individuals carried sequence variations in F8, but not in F9. These
      results can be used as a reference dataset for molecular diagnosis of hemophilia
      A and B, particularly in Korea.

PMID- 24086942
TI  - Hereditary hemolytic anemia in Korea from 2007 to 2011: A study by the Korean
      Hereditary Hemolytic Anemia Working Party of the Korean Society of Hematology.
AB  - BACKGROUND: The number of patients diagnosed with hereditary hemolytic anemia
      (HHA) has increased since the advent of novel diagnostic techniques that
      accurately identify this disorder. Here, we report data from a survey on the
      prevalence and characteristics of patients diagnosed with HHA in Korea from 2007
      to 2011. METHODS: Information on patients diagnosed with HHA in Korea and their
      clinical and laboratory results were collected using a survey questionnaire.
      Globin gene and red blood cell (RBC) enzyme analyses were performed. In addition,
      we analyzed data collected by pediatricians. RESULTS: In total, 195 cases of HHA
      were identified. Etiologies identified for HHA were RBC membranopathies,
      hemoglobinopathies, and RBC enzymopathies, which accounted for 127 (64%), 39
      (19.9%), and 26 (13.3%) cases, respectively. Of the 39 patients with
      hemoglobinopathies, 26 were confirmed by globin gene analysis, including 20
      patients with beta-thalassemia minor, 5 patients with alpha-thalassemia minor,
      and 1 patient with unstable hemoglobin disease. CONCLUSION: The number of
      patients diagnosed with hemoglobinopathies and RBC enzymopathies has increased
      considerably since the previous survey on HHA in Korea, dated from 1997 to 2006.
      This is likely the result of improved diagnostic techniques. Nevertheless, there
      is still a need for more sensitive diagnostic tests utilizing flow cytometry and
      for better standardization of test results to improve the accuracy of diagnosis
      of RBC membranopathies in Korea. Additionally, more accurate assays for the
      identification of RBC enzymopathies are warranted.

PMID- 24086943
TI  - Unexpected red cell antibody detection by conditional combination of LISS/Coombs
      and NaCl/Enzyme gel tests at a tertiary care hospital in Korea: A 5-year study.
AB  - BACKGROUND: A combination of the LISS/Coombs and enzyme methods is recommended
      for identifying unexpected antibodies. However, many laboratories in which tests
      are to be performed within the limits of medical fees covered by insurance, use
      only the LISS/Coombs method because the permissible medical fee is low as
      compared to the price of reagents required for both methods. The NaCl/Enzyme gel
      is used as a secondary assay when the LISS/Coombs gel test yields inconclusive
      results. We compared the frequency of unexpected antibody identified by
      LISS/Coombs gel with that obtained by the conditional combination of LISS/Coombs
      and NaCl/Enzyme gels. We aimed at establishing evidence-based guidelines for
      antibody testing. METHODS: From June 2007 to June 2012, antibody screening was
      performed for 69,986 samples; subsequently, antibodies were identified in samples
      showing positive screening results. These initial screenings and identifications
      were performed using the LISS/Coombs gel. We considered the results
      "inconclusive" when specific antibodies were not identified or reactions were too
      weak for accurate interpretation. For the inconclusive samples, we subsequently
      used NaCl/Enzyme gels. RESULTS: The overall detection rate of unexpected
      antibodies was 1.23%. Among the samples analyzed using NaCl/Enzyme gels, 40.2%
      showed results different from those obtained using LISS/Coombs gels. Moreover,
      41.9% of samples with nonspecific reactions in LISS/Coombs gels showed clinically
      significant Rh or Kidd antibodies with NaCl/Enzyme gels. CONCLUSION: Considering
      both patient safety and cost effectiveness, we recommend the use of conditional
      combination of LISS/Coombs and NaCl/Enzyme gels for antibody detection,
      especially in laboratories that must perform tests within an established budget.

PMID- 24086944
TI  - A case of myelodysplastic syndrome with marked eosinophilia showing favorable
      prognosis.
AB  - Myelodysplastic syndrome (MDS) with eosinophilia is a rare condition and has yet
      to be classified under the 2008 World Health Organization classification.
      However, reports have described the prognostic significance of chronic persistent
      eosinophilia in MDS. Here, we report a case of a 67-year-old woman who was
      admitted to the hospital in July 2007 with generalized weakness, dizziness, and
      dyspnea on exertion persisting for 5 years. In the initial investigation,
      eosinophilia (22.1%) in peripheral blood and an increased proportion of
      eosinophils (5.6%) in normocellular bone marrow with dysplastic megakaryocytes
      and erythroid cells were noted. Eosinophilia was continuously detected during
      follow-up over 3 years. In a second bone marrow examination in August 2010,
      hypercellular bone marrow with similar features was observed. These findings led
      to the diagnosis of MDS with chronic persistent eosinophilia. To increase
      awareness of the prognostic significance of MDS with chronic eosinophilia, here
      we report a slow-progressing case of MDS with chronic persistent eosinophilia
      lasting over 6 years. 

PMID- 24086945
TI  - BK virus encephalitis without concurrent hemorrhagic cystitis in an allogeneic
      hematopoietic stem cell transplant recipient.

PMID- 24086946
TI  - Concomitant transformation of monoclonal gammopathy of undetermined significance
      to multiple myeloma and of essential thrombocythemia to acute biphenotypic
      leukemia 37 years after initial diagnosis.

PMID- 24086947
TI  - Waldenstrom's macroglobulinemia presenting with lytic bone lesions: a rare
      presentation.

PMID- 24086948
TI  - Relationship between bortezomib-containing regimens and the incidence of
      tuberculosis in patients with myeloma.

PMID- 24086949
TI  - Afatinib for the treatment of patients with EGFR-positive non-small cell lung
      cancer.
AB  - Epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs) are
      valuable treatments for EGFR-mutated non-small cell lung cancer (NSCLC). Anti
      EGFR antibodies are widely used in the treatment of head and neck squamous cell
      carcinomas (HNSCC) and in KRAS wild-type colorectal cancer. The first-generation,
      reversible EGFR inhibitors erlotinib and gefitinib in the first-line setting
      provide superior progression-free survival and quality of life compared to
      conventional chemotherapy in NSCLC harboring activating EGFR mutations. However,
      these therapies eventually fail and new options are needed. Afatinib is a novel
      irreversible inhibitor of the ErbB family members EGFR, tyrosine kinase-type cell
      surface receptors HER2 and HER4. It shows preclinical efficacy in NSCLC with
      common EGFR-activating mutations and the T790M mutation typically associated with
      EGFR TKI resistance. Preclinical activity is seen in other tumor types as well,
      including HNSCC. Clinically, afatinib has been evaluated in the broad-reaching
      LUX Lung trial program, with significant activity seen in the first and later
      line settings. It is also under investigation in multiple other tumor types. This
      review will stress on afatinib's preclinical pharmacology, pharmacokinetics and
      clinical activity with a focus on NSCLC. 

PMID- 24086950
TI  - Lixisenatide for the treatment of type 2 diabetes.
AB  - Lixisenatide (trade name Lyxumia(r)), a short-acting glucagon-like peptide 1
      receptor (GLP-1R) agonist, was approved for the treatment of type 2 diabetes by
      the European Medicines Agency in early 2013. In preclinical investigations,
      acceptable toxicity and carcinogenicity profiles were demonstrated, as well as
      pancreatic beta cell-preserving actions and favorable effects on glycemic
      control. Following subcutaneous administration in humans, lixisenatide displays
      linear pharmacokinetics and an absorption-dependent elimination half-life of 2-3
      hours. In clinical trials of up to 1 year duration in patients with type 2
      diabetes, treatment with lixisenatide alone and in combination with insulin and
      various oral antidiabetics conferred significant reductions in HbA1c, fasting and
      postprandial plasma glucose. In direct comparison with the other GLP-1R agonists
      on the market (exenatide and liraglutide), lixisenatide appears to be less
      efficient, or at best non-inferior in terms of reducing HbA1c, fasting plasma
      glucose and body weight. Nevertheless, lixisenatide confers fewer adverse events
      than the other currently marketed GLP-1R agonists, while exhibiting a clinically
      valuable effect on postprandial hyperglycemia. 

PMID- 24086951
TI  - Pomalidomide for patients with multiple myeloma.
AB  - Multiple myeloma is a malignancy of plasma cells in the bone marrow. Currently,
      multiple myeloma is not considered curable, but it is treatable with different
      strategies that can combine chemotherapy with autologous hematopoietic stem cell
      transplantation. Pomalidomide is an orally active thalidomide analogue that has a
      pleiotropic mechanism of action involving oncolytic, antiangiogenic,
      immunomodulatory and anti-inflammatory activities. Pomalidomide is extensively
      metabolized, mainly by the cytochrome P450 3A4 and 1A2 pathways. The safety and
      efficacy of pomalidomide combined with dexamethasone has been demonstrated in a
      phase III trial for the treatment of multiple myeloma patients,
      relapsed/resistant to bortezomib and lenalidomide. Adverse events that were
      mainly related to myelosuppression, were manageable. Pomalidomide has orphan drug
      status both in the U.S. and Europe for multiple myeloma. It was approved by the
      U.S. Food and Drug Administration as Pomalyst(r) for the treatment of multiple
      myeloma last February, and recently approved in Europe in August.

PMID- 24086952
TI  - Contemporary drug therapies for multiple myeloma.
AB  - Multiple myeloma (MM) is an incurable disease characterized by the proliferation
      of plasma cells. The survival in MM patients has improved significantly in the
      past decade due to the introduction of novel agents. In this review, we focus on
      novel agents used in MM, including immunomodulatory drugs (thalidomide,
      lenalidomide and pomalidomide), proteasome inhibitors (bortezomib, carfilzomib,
      marizomib and ixazomib citrate), monoclonal antibodies (elotuzumab, siltuximab,
      daratumumab and BT-062), and drugs affecting an interaction with the tumor
      microenvironment (anti-VLA4 monoclonal antibody, chemokine CXCR4 inhibitor AMD
      3100 and selectin inhibitor GMI-1070). We discuss their mechanism of action,
      preclinical and clinical outcome in the treatment of MM. Although the development
      of novel agents has improved the outcomes of MM treatment, most of the patients
      will still relapse and become refractory to therapy due to development of drug
      resistance. A better understanding of the biological mechanisms of MM
      progression, including cellular and molecular events in the MM cells and in their
      bone marrow microenvironment, is warranted to provide new therapeutic targets and
      develop new drugs and therapeutic strategies to treat MM. 

PMID- 24086953
TI  - A report from the European Society of Cardiology Congress 2013 (August 31
      September 4, 2013 - Amsterdam, the Netherlands).
AB  - Many are the diseases that can affect the heart and the vessels, most of which
      were discussed during the European Society of Cardiology Congress 2013 in
      Amsterdam. With an attendance of almost 30,000 delegates buzzing the halls of the
      RAI convention center, Amsterdam was the capital of cardiologic science this
      summer, and a big challenge for any attendee trying to get the most out of all
      the oral and poster sessions missing the minimum of new science being presented.
      Thomson Reuters CortellisTM supplements the information for any scientist who
      missed an important session, with a particular focus on new investigational
      drugs, many of them still in preclinical research, which will certainly impact
      how cardiovascular disorders are treated in a foreseeable future. Clinical and
      preclinical research advance to bring novel therapeutic targets, new drugs and
      new insight into patient characteristics requiring particular treatment
      approaches. This report is a sample of the new science discussed during the 5
      days of meetings. 

PMID- 24087775
TI  - The semantics of lupus: what is in a name?

PMID- 24087776
TI  - Riding the wave.

PMID- 24087777
TI  - The Physician Compare web site.

PMID- 24087778
TI  - Metastatic eccrine porocarcinoma.
AB  - Eccrine porocarcinoma (EP) is a rare malignant tumor arising from the
      intraepidermal sweat duct. The lesions have a varied clinical appearance and
      usually are asymptomatic. In reported cases, metastasis is rare but can be
      devastating when it occurs. We describe an unusual case of EP in a patient who
      presented with metastatic disease. New-onset exquisite pain prompted his
      evaluation. This case and review of metastatic disease is presented to raise
      awareness of this tumor, its varied clinical presentations, differential
      diagnosis, and management. 

PMID- 24087780
TI  - Acantholytic dyskeratosis occurring within an epidermal nevus.
AB  - A 25-year-old woman presented with a large area of flesh-colored verrucous
      plaques following the lines of Blaschko on the left side of the body that had
      been present since 6 months of age. The plaques had been stable and grew
      proportionately with the patient's body until she reached 20 years of age when
      they began to thicken and enlarge. Her medical and family history was
      unremarkable. A shave biopsy revealed a papillomatous epidermis with 3 discrete
      foci of acantholytic dyskeratosis, with corps ronds and grains that were similar
      to the histologic findings of Darier disease (DD). Epidermolytic hyperkeratosis
      was not identified. Our patient's lack of a family history of DD, early-onset
      disease, and linear presentation along the lines of Blaschko all favored a
      diagnosis of acantholytic dyskeratotic epidermal nevi (ADEN) versus localized DD.

PMID- 24087779
TI  - Syphilis, leprosy, and human immunodeficiency virus coinfection: a challenging
      diagnosis.
AB  - The association between syphilis, leprosy, and human immunodeficiency virus (HIV)
      is not well documented, and the emergence of isolated cases raises the interest
      and indicates that this triple coinfection can occur. We report the case of a 42
      year-old man from Rio de Janeiro, Brazil, who presented with erythematous papules
      on the trunk, back, and upper and lower extremities; an erythematous plaque on
      the upper abdomen; and an erythematous violaceous plaque on the right thigh with
      altered sensitivity. Laboratory investigation showed a reagent VDRL test (1:512)
      and positive test results for Treponema pallidum hemagglutination. Treatment with
      benzathine penicillin (2,400,000 U intramuscularly) was started (2 doses 1 week
      apart). On follow-up 40 days later, the lesions showed partial improvement with
      persistence of the plaques on the right thigh and upper abdomen as well as a new
      similar plaque on the back. Further laboratory examinations showed negative
      bacilloscopy, positive HIV test, and histologic findings consistent with
      tuberculoid leprosy. The patient was started on multidrug therapy for
      paucibacillary leprosy with clinical improvement; the patient also was monitored
      by the HIV/AIDS department. We emphasize the importance of clinical suspicion for
      a coinfection case despite the polymorphism of these diseases as well as the
      precise interpretation of laboratory and histopathology examinations to correctly
      manage atypical cases. 

PMID- 24087781
TI  - Sclerema neonatorum treated with intravenous immunoglobulin: a case report and
      review of treatments.
AB  - Sclerema neonatorum (SN) is a rare neonatal panniculitis that typically develops
      in severely ill, preterm newborns within the first week of life and often is
      fatal. It usually occurs in preterm newborns with delivery complications such as
      respiratory distress or maternal complications such as eclampsia. Few clinical
      trials have been performed to address potential treatments. Successful treatment
      has been achieved via exchange transfusion (ET), but its use in neonates is
      declining. Similar to ET, intravenous immunoglobulin (IVIG) enhances both humoral
      and cellular immunity and thus may decrease mortality associated with SN. We
      report a case of SN in a term newborn who subsequently developed septicemia.
      Biopsy showed subcutaneous, needle-shaped clefts without associated necrosis,
      inflammation, or calcifications. Treatment with IVIG led to notable but short
      term clinical improvement. Sclerema neonatorum remains a poorly understood and
      difficult to treat neonatal disorder. Although IVIG did not prevent our patient's
      death, further studies are needed to determine its clinical utility in the
      treatment of this rare disorder. 

PMID- 24087782
TI  - Management and prevention of varicella-zoster virus infection in pregnancy: a
      case report and review of the literature.
AB  - Primary infection with varicella-zoster virus (VZV) during pregnancy can lead to
      devastating outcomes for both the mother and fetus. We describe a case of VZV
      infection in a pregnant woman who presented at 38 weeks' gestation. We also
      review the literature regarding management and prevention. Varicella-zoster virus
      associated pneumonia in the mother is important to recognize. Outcomes in the
      newborn largely are dependent on gestational age at the time of infection.
      Prevention is paramount to management. 

PMID- 24087783
TI  - Targetoid hemosiderotic hemangioma: a case report of multiple asymptomatic
      lesions.
AB  - Targetoid hemosiderotic hemangioma (THH) is a benign vascular tumor characterized
      by a central violaceous papule with a clear periphery bordered by an ecchymotic
      ring. Originally coined by its characteristic halo appearance with hemosiderin
      deposits, not all THHs have this classic halo or hemosiderin composition. We
      report a unique case of THH in which the patient presented with multiple lesions
      with no prior trauma. Multiple THH lesions have been linked to minor trauma;
      however, the presence of 4 concurrent lesions with the absence of trauma makes
      this THH presentation atypical and unique. 

PMID- 24087784
TI  - Addisonian pigmentation and vitamin B12 deficiency: a case series and review of
      the literature.
AB  - Skin changes associated with vitamin B12 deficiency are common. In most cases,
      patients present primarily with systemic involvement (eg, megaloblastic anemia
      and/or neurologic effects), and additional cutaneous changes related to the
      diagnosis are noted as incidental findings. The role of vitamin B12 deficiency in
      the etiology of Addisonian pigmentation has not been well studied. We discuss the
      importance of testing vitamin B12 levels in patients who present for evaluation
      of generalized hyperpigmentation. Various cutaneous changes associated with
      vitamin B12 deficiency also are reviewed.

PMID- 24087785
TI  - Futcher lines: a case report in pregnancy and literature review.
AB  - Pigmentary demarcation lines are common, especially in individuals with darker
      skin types. Type B pigmentary demarcation lines (Futcher lines) involve the
      posterior lower extremities and can be associated with pregnancy, often with
      spontaneous resolution after delivery. The pathogenesis of pigmentary demarcation
      lines remains unknown; however, neurogenic inflammation and/or mosaicism are
      thought to play a role in their development. We report a case of type B
      pigmentary demarcation lines in pregnancy and provide a review of the literature.

PMID- 24087786
TI  - Axillary granular parakeratosis.

PMID- 24087787
TI  - Clear cell acanthoma.

PMID- 24087788
TI  - Neonatal skin: a dynamic adaptation process.

PMID- 24087791
TI  - Identification of FHL1 as a therapeutic target for Duchenne muscular dystrophy.
AB  - Utrophin is a potential therapeutic target for the fatal muscle disease, Duchenne
      muscular dystrophy (DMD). In adult skeletal muscle, utrophin is restricted to the
      neuromuscular and myotendinous junctions and can compensate for dystrophin loss
      in mdx mice, a mouse model of DMD, but requires sarcolemmal localization. NFATc1
      mediated transcription regulates utrophin expression and the LIM protein, FHL1
      which promotes muscle hypertrophy, is a transcriptional activator of NFATc1. By
      generating mdx/FHL1-transgenic mice, we demonstrate that FHL1 potentiates NFATc1
      activation of utrophin to ameliorate the dystrophic pathology. Transgenic FHL1
      expression increased sarcolemmal membrane stability, reduced muscle degeneration,
      decreased inflammation and conferred protection from contraction-induced injury
      in mdx mice. Significantly, FHL1 expression also reduced progressive muscle
      degeneration and fibrosis in the diaphragm of aged mdx mice. FHL1 enhanced NFATc1
      activation of the utrophin promoter and increased sarcolemmal expression of
      utrophin in muscles of mdx mice, directing the assembly of a substitute utrophin
      glycoprotein complex, and revealing a novel FHL1-NFATc1-utrophin signaling axis
      that can functionally compensate for dystrophin. 

PMID- 24087792
TI  - Dynamic changes in DNA methylation and hydroxymethylation when hES cells undergo
      differentiation toward a neuronal lineage.
AB  - DNA methylation and hydroxymethylation have been implicated in normal development
      and differentiation, but our knowledge is limited about the genome-wide
      distribution of 5-methylcytosine (5 mC) and 5-hydroxymethylcytosine (5 hmC)
      during cellular differentiation. Using an in vitro model system of gradual
      differentiation of human embryonic stem (hES) cells into ventral midbrain-type
      neural precursor cells and terminally into dopamine neurons, we observed dramatic
      genome-wide changes in 5 mC and 5 hmC patterns during lineage commitment. The 5
      hmC pattern was dynamic in promoters, exons and enhancers. DNA hydroxymethylation
      within the gene body was associated with gene activation. The neurogenesis
      related genes NOTCH1, RGMA and AKT1 acquired 5 hmC in the gene body and were up
      regulated during differentiation. DNA methylation in the promoter was associated
      with gene repression. The pluripotency-related genes POU5F1, ZFP42 and HMGA1
      acquired 5 mC in their promoters and were down-regulated during differentiation.
      Promoter methylation also acted as a locking mechanism to maintain gene
      silencing. The mesoderm development-related genes NKX2-8, TNFSF11 and NFATC1
      acquired promoter methylation during neural differentiation even though they were
      already silenced in hES cells. Our findings will help elucidate the molecular
      mechanisms underlying lineage-specific differentiation of pluripotent stem cells
      during human embryonic development. 

PMID- 24087793
TI  - Two classes of ovarian primordial follicles exhibit distinct developmental
      dynamics and physiological functions.
AB  - In the mammalian ovary, progressive activation of primordial follicles serves as
      the source of fertilizable ova, and disorders in the development of primordial
      follicles lead to various ovarian diseases. However, very little is known about
      the developmental dynamics of primordial follicles under physiological
      conditions, and the fates of distinct populations of primordial follicles also
      remain unclear. In this study, by generating the Foxl2-CreER(T2) and Sohlh1
      CreER(T2) inducible mouse models, we have specifically labeled and traced the in
      vivo development of two classes of primordial follicles, the first wave of
      simultaneously activated follicles after birth and the primordial follicles that
      are gradually activated in adulthood. Our results show that the first wave of
      follicles exists in the ovaries for ~3 months and contributes to the onset of
      puberty and to early fertility. The primordial follicles at the ovarian cortex
      gradually replace the first wave of follicles and dominate the ovary after 3
      months of age, providing fertility until the end of reproductive life. Moreover,
      by tracing the time periods needed for primordial follicles to reach various
      advanced stages in vivo, we were able to determine the exact developmental
      dynamics of the two classes of primordial follicles. We have now revealed the
      lifelong developmental dynamics of ovarian primordial follicles under
      physiological conditions and have clearly shown that two classes of primordial
      follicles follow distinct, age-dependent developmental paths and play different
      roles in the mammalian reproductive lifespan. 

PMID- 24087795
TI  - The double scandal of insulin.

PMID- 24087794
TI  - WNT/beta-catenin signalling is activated in aldosterone-producing adenomas and
      controls aldosterone production.
AB  - Primary aldosteronism (PA) is the main cause of secondary hypertension, resulting
      from adrenal aldosterone-producing adenomas (APA) or bilateral hyperplasia. Here,
      we show that constitutive activation of WNT/beta-catenin signalling is the most
      frequent molecular alteration found in 70% of APA. We provide evidence that
      decreased expression of the WNT inhibitor SFRP2 may be contributing to
      deregulated WNT signalling and APA development in patients. This is supported by
      the demonstration that mice with genetic ablation of Sfrp2 have increased
      aldosterone production and ectopic differentiation of zona glomerulosa cells. We
      further show that beta-catenin plays an essential role in the control of basal
      and Angiotensin II-induced aldosterone secretion, by activating AT1R, CYP21 and
      CYP11B2 transcription. This relies on both LEF/TCF-dependent activation of AT1R
      and CYP21 regulatory regions and indirect activation of CYP21 and CYP11B2
      promoters, through increased expression of the nuclear receptors NURR1 and NUR77.
      Altogether, these data show that aberrant WNT/beta-catenin activation is
      associated with APA development and suggest that WNT pathway may be a good
      therapeutic target in PA. 

PMID- 24087796
TI  - End-of-life communication: let's talk about death.

PMID- 24087797
TI  - Likelihood of aneurysmal subarachnoid haemorrhage in patients with normal
      unenhanced CT, CSF xanthochromia on spectrophotometry and negative CT
      angiography.
AB  - BACKGROUND: Patients with suspected subarachnoid haemorrhage, a normal
      noncontrast computed tomography (CT) and cerebrospinal fluid (CSF) evidence of
      haemoglobin breakdown products often undergo CT angiography (CTA). If this is
      normal, then invasive catheter angiography may be offered. In current clinical
      practice, haemoglobin breakdown products are detected by spectrophotometry rather
      than visible xanthochromia, and CTA is performed on multidetector scanners. The
      aim of this study was to determine if such patients should still have a catheter
      angiography, given the associated risks. METHODS: Patients positive for CSF
      spectrophotometry (n=26) were retrospectively identified from the clinical
      biochemistry information system and imaging data from the electronic radiology
      records were reviewed. Discharge letters were consulted to relate the
      biochemistry and radiology results to the final diagnosis. RESULTS: 15 patients
      with CT angiography were found. Nine patients had normal CT angiography. No
      causative aneurysms had been missed. One patient had small, coincidental
      aneurysms missed on initial reading of the CTA. CONCLUSION: The likelihood of a
      clinically significant aneurysm in a patient who is CT negative, lumbar puncture
      positive and CTA negative is low. Double reporting of negative CT angiograms may
      be advisable.

PMID- 24087798
TI  - A pilot survey of decisions by acute medicine staff after thunderclap headache.
AB  - INTRODUCTION AND AIMS: Traditionally, neurologically pristine patients with a
      thunderclap headache are investigated with a non-contrast computed tomography
      (CT) brain scan, which if negative is followed by a lumbar puncture (LP) to
      exclude important secondary causes, particularly subarachnoid haemorrhage (SAH).
      However, misdiagnosis of such patients is still a cause of significant human and
      financial cost and a regular reason for medical litigation. This study explores
      the approach of emergency medicine and acute medicine clinicians to the
      investigation of a patient with thunderclap headache. METHODS: Clinicians were
      invited to complete an online survey based on a clinical vignette of a 45-year
      old man presenting with a thunderclap headache who had a pristine neurological
      examination. RESULTS: A total of 160 clinicians responded. The majority (89%)
      elected to perform a non-contrast CT brain as their first investigation, though
      five clinicians discharged the patient without investigation. If the CT was
      negative, only 84% would then proceed to LP, but 20% would undertake this
      investigation before 12 hours from headache onset. CONCLUSIONS: Most clinicians
      investigate neurologically intact patients with thunderclap headache following a
      CT/LP strategy, but deviations from recommended practice are common.

PMID- 24087800
TI  - A curious case of unilateral spider nevi, cirrhosis and stroke: unilateral nevoid
      telangiectasia syndrome.
AB  - A 55-year-old Caucasian man presented with unilateral right facial spider nevi.
      Relevant medical history included a right-sided cerebrovascular accident (CVA) in
      1997 and decompensated alcoholic liver disease, diagnosed in 2007. The literature
      describes approximately 100 cases of unilateral spider nevi associated with
      different aetiologies, grouped under 'unilateral nevoid telangiectasia syndrome'
      (UNTS). This is a rare presentation of a commonly observed sign in clinical
      practice. This case offers an opportunity to explore the origins of spider nevi
      and highlights the benefit of sharing knowledge in order to help elucidate the
      potential mechanisms underlying common signs. 

PMID- 24087799
TI  - Views of the chairs of Scottish health boards on engagement with quality
      management and comparisons with English trusts.
AB  - OBJECTIVE: To describe the views of the chairs of Scottish health boards on the
      engagement of their boards with healthcare quality and to compare them with the
      views of the chairs of boards of English acute trusts. The focus of the Scottish
      Health Boards is on providing and commissioning care, while in England the acute
      trusts only provide care. METHODS: We mailed a questionnaire, based on one used
      in England, to the 14 health board chairs in NHS Scotland in January 2011. The
      results were compared with the results of a similar questionnaire given to
      English acute trust chairs in 2009. RESULTS: Most chairs in Scotland (67%)
      prioritised oversight of quality. Quality is considered at most Board meetings
      (92%), taking over 20% of time for 69% of chairs. Most boards have local quality
      targets and feedback quality data to staff. Compared with England, boards in
      Scotland meet less frequently and focus less on quality (shorter discussions,
      less frequent data review, fewer local targets) but they are more optimistic
      about their board's performance. CONCLUSIONS: Although most chairs of Scottish
      boards view quality as a priority, they pay less attention to it than chairs in
      England, possibly due to their additional role in commissioning care.

PMID- 24087801
TI  - Reversible cerebral vasoconstriction syndrome.
AB  - Reversible cerebral vasoconstriction syndrome (RCVS) is an underdiagnosed
      condition which usually presents as severe headache with or without neurological
      deficit. We report the case of a 55-year-old woman who presented with headache
      and multifocal intracerebral haemorrhage. We review the literature regarding the
      presentation, pathophysiology and management of RCVS and discuss how to
      differentiate it from cerebral vasculitis. 

PMID- 24087802
TI  - Cousin marriage and congenital anomalies in a multiethnic birth cohort.

PMID- 24087803
TI  - Working the night shift: a necessary time for training or a risk to health and
      safety?
AB  - The European Working Time Directive (EWTD) limits excessive night shifts and
      restricts the working week to no more than 48 hours. The underlying rationale is
      to minimise the health risks to all workers. Here we debate the impact of night
      rotas for doctors-in-training on patient safety and medical education; when the
      EWTD was agreed these topics may not have been considered, either systematically
      or objectively. The impacts of diurnal rhythms on human functions affect all
      night workers, but the nature of rostered medical and surgical work has little
      precedent in other industries or even in the contracts of other healthcare staff.
      For example, rostered night duties need to be distinguished from permanent night
      shift work. On-call medical night work from training doctors is generally
      required for short periods and usually involves fewer patients. It is an
      important time in training, where clinical responsibility and decision-making can
      be matured in a supervised setting. To comply with the EWTD most hospitals have
      adopted rota patterns that aim to cover the clinical needs, while ensuring no
      doctor works for more than 48 hours in an average working week. To monitor this
      process longterm studies are necessary to evaluate effects on a doctor's health
      and on patient care generally. The EWTD has also led to a loss of continuity of
      patient care; does this really matter? 

PMID- 24087804
TI  - Human immunodeficiency virus infection and kidney disease.
AB  - Since the introduction of highly active antiretroviral therapy (HAART) in 1996,
      mortality in patients with human immunodeficiency virus (HIV) infection has
      decreased markedly. As a result, morbidity from other chronic conditions such as
      kidney, liver and heart disease is increasing. This is in part as a natural
      consequence of ageing, and in part due to the higher risk of solid organ failure
      in these individuals. This higher risk is related to the co-morbidities
      associated with HIV infection and to the metabolic consequences of drug therapy.
      Kidney disease is an important cause of morbidity and mortality in patients with
      HIV infection and encompasses a range of clinical presentations including acute
      kidney injury, chronic kidney disease (CKD), and end-stage kidney disease. Black
      race is the most important predictor of kidney disease in HIV-infected persons
      due to both genetic and modifiable causes. HIVassociated nephropathy (HIVAN) is
      caused by viral infection of the renal epithelium and, although decreasing in
      incidence, remains the most common cause of CKD in HIV-infected persons. In
      addition to HIVAN, a wide spectrum of other histopathological presentations, many
      of which are immune complex-mediated, is increasingly recognised. Clinicians who
      treat these patients should be aware of the nephrotoxic potential of several
      commonly used medications, particularly antiviral agents, and also the need to
      dose-adjust medication in renal impairment. The increased life expectancy of
      patients with HIV and end-stage kidney disease has meant that kidney
      transplantation is increasingly an option. Results from carefully conducted
      prospective studies are promising, at least in the short term. 

PMID- 24087805
TI  - Cutaneous allergy.
AB  - Cutaneous allergy encompasses a broad spectrum of clinical presentations with
      complex underlying immunological mechanisms. Allergy may be considered to play a
      role in disorders that include atopic dermatitis, contact dermatitis, urticaria,
      angioedema, anaphylaxis and adverse drug reactions. The skin phenotypes
      associated with allergy are more commonly exhibited in non-allergic disease and
      so a high proportion of patients who consider themselves allergic in truth have
      other, nonallergic explanations for their presentation. Investigations may help
      to delineate those individuals who are more likely to have true allergy, but
      tests currently available have significant limitations and are open to easy
      misinterpretation. As a consequence, any investigations are best carried out by
      someone experienced in managing patients with potentially allergic disorders. 

PMID- 24087806
TI  - Management of hyperkalaemia.
AB  - Hyperkalaemia, an elevated extracellular fluid potassium concentration, is a
      common electrolyte disorder and is present in 1-10% of hospitalised patients.
      Elevated serum potassium concentrations are usually asymptomatic but may be
      associated with electrocardiogram (ECG) changes. Hyperkalaemia occasionally leads
      to life-threatening cardiac arrhythmias. Prompt recognition of this disorder,
      patient risk management and administration of appropriate treatment can prevent
      serious cardiac complications of hyperkalaemia. Further assessment of the
      underlying basis for hyperkalaemia usually reveals a problem with renal potassium
      excretion (rather than transcellular shift of potassium or excess potassium
      intake). Reduced potassium excretion is typically associated with decreased
      potassium secretion in the aldosterone-sensitive distal nephron of the kidney.
      Common causes for hyperkalaemia include kidney failure, limited delivery of
      sodium and water to the distal nephron and drugs that inhibit the renin
      angiotensin-aldosterone system. Treatment of life-threatening hyperkalaemia
      (particularly those patients with ECG changes) involves administration of
      intravenous calcium salts to stabilise the resting cardiac membrane potential.
      The potassium concentration can be lowered by administration of intravenous
      insulin combined with an infusion of glucose to stimulate intracellular uptake of
      potassium. Nebulised beta-2 adrenoceptor agonists can augment the effects of
      intravenous insulin and glucose pending more definitive management of the
      recurrent hyperkalaemia risk. Additional management steps include stopping
      further potassium intake and careful review of prescribed drugs that may be
      adversely affecting potassium homeostasis. Changes to prescribing systems and an
      agreed institutional protocol for management of hyperkalaemia can improve patient
      safety for this frequently encountered electrolyte disorder. 

PMID- 24087807
TI  - Renal medicine in the 'real world'.
AB  - The Renal Symposium was held on 12 October 2012 at the Royal College of
      Physicians of Edinburgh. 

PMID- 24087808
TI  - The history of osteoporosis: why do Egyptian mummies have porotic bones?
AB  - Paleopathologists have identified osteoporosis in ancient skeletons and modern
      physicians and scientists have identified risk factors for osteoporosis today,
      but they are not clearly linked, making it more difficult to clarify the causes
      of osteoporosis in the past. The evidence for osteoporosis in the remote past,
      its causes, and the management of this disease is reviewed in the light of
      evolving and improving diagnostic modalities, more precise definitions, and the
      recent rapid expansion of therapeutic options. While the specific effects of
      parity and lactation on the development of osteoporosis are still not entirely
      clear, duration of reproductive span and age at first pregnancy appear to be
      significant predisposing factors. 

PMID- 24087809
TI  - The ancestors of Norman Bethune (1890-1939) traced back to the Bethunes of Skye,
      leading members of the MacBeth/Beaton medical dynasty.
AB  - Norman Bethune became famous through his work in the Spanish Civil War, his
      advocacy of socialised medicine in North America and his association with Mao
      Zedong's revolutionary movement in China. It has been suggested that he may have
      been descended from the Bethune or Beaton medical dynasty, who for generations
      served as physicians to kings of Scotland, the Lords of the Isles and to some of
      the larger Scottish clans. This paper traces his lineage back to the Isle of
      Skye. In the absence of old parish records as aids to tracing genealogy, other
      available evidence has confirmed that Bethune was indeed in the direct line of
      descent from the Bethunes or Beatons of Husabost, in Skye, one of the largest
      branches of this medical kindred, who were physicians to the MacLeods of
      Dunvegan. 

PMID- 24087810
TI  - La methode curative des playes de la teste humaine.

PMID- 24087811
TI  - The effect of rest on raised blood pressure.

PMID- 24087812
TI  - Sir Ludwig Guttmann: his neurology research and his role in the treatment of
      peripheral nerve injuries, 1939-1944.
AB  - Ludwig Guttmann spent five crucial years in Oxford between 1939 and 1944,
      carrying out fundamental research in peripheral nerve regeneration and the
      rehabilitation of patients with peripheral nerve injuries. He worked with Peter
      Medawar, John Zachary Young, Graham Weddell, Ernst Gutmann and others. He
      dismissed this period of his life, but the experience he gained was critical for
      his subsequent career in rehabilitating spinal injury patients. 

PMID- 24087813
TI  - What does it mean for a treatment to 'work?'.

PMID- 24087814
TI  - Archy strives for an elusive social acceptance.

PMID- 24087815
TI  - The Brown Kenya medical exchange program: part 2.

PMID- 24087816
TI  - Research components of the Brown Kenya Program: a personal and professional
      perspective.

PMID- 24087817
TI  - Challenges of developing a formal subspecialty pulmonary training program in
      Kenya.

PMID- 24087818
TI  - Gastroenterology in Eldoret: make the journey; share the knowledge.

PMID- 24087819
TI  - Return to Kenya after 37 years: cultural and medical observations.

PMID- 24087820
TI  - Building a diabetes educational and clinical program in Kenya.

PMID- 24087821
TI  - Two Kenyan physicians studying at Brown share perspectives.

PMID- 24087822
TI  - Opportunities for improving legislative public health policy in Rhode Island
      through evidence-based education.
AB  - The Rhode Island General Assembly considers nearly 3000 bills yearly--spanning
      the entire range of issues related to state government and legislative policy.
      This review analyzes the modest number of 40 "health-related" bills introduced
      during the 2009 session. It is often not clear to what extent these proposals
      consistently received analysis by both informed and independent organizations or
      experts regarding their "evidence-based" foundations. Only 25 of these bills
      received a committee hearing, and eventually become law. Hence, there may be a
      reasonable opportunity for expert, non-partisan organizations to provide the
      General Assembly with information related to proposed legislation on a routine or
      "as requested" basis. This study provides a systematic analysis of this degree of
      effort based on data regarding health- related legislation proposed during the
      2009 session of the RI General Assembly.

PMID- 24087823
TI  - Lemierre's syndrome in 15-year-old female.

PMID- 24087824
TI  - The inflammatory regulation of tubal beta-catenin expression in human ectopic
      pregnancy: is it too early to propose a cause-and-effect relationship?

PMID- 24087825
TI  - Reply: the inflammatory regulation of tubal beta-catenin expression in human
      ectopic pregnancy: is it too early to propose a cause-and-effect relationship?

PMID- 24087826
TI  - The benefits of high resolution mass spectrometry in environmental analysis.
AB  - The benefits of high resolution mass spectrometry (HRMS) are well known and
      widely realized in various applications; however, HRMS is very rarely utilized in
      environmental GC/MS analyses. It is assumed that low resolution GC/MS provides
      adequate and reliable results in the majority of cases dealing with priority
      pollutants and other volatile and semivolatile compounds. As environmental issues
      become more and more important in modern society and new generations of high
      resolution and high mass accuracy mass spectrometers become available, it is
      quite reasonable to expect improvements in sensitivity, reliability and quantity
      of information provided by GC/MS analyses. This article demonstrates the
      advantages of high resolution GC/MS for qualitative and quantitative
      environmental analyses including targeted and non-targeted approaches as well as
      de novo structural elucidation of analytes not present in commercial libraries.
      Most of the examples presented here involve the GC/MS analysis of snow samples
      collected in 2012 and 2013 in Moscow, Russia. 

PMID- 24087827
TI  - Rapid separation of synthetic oligonucleotides on polymer modified capillary
      surfaces using short-end injection capillary electrophoresis in free solution.
AB  - Here we use short-end electrokinetic injection capillary electrophoresis (CE) to
      investigate the free solution mobility of short strands of double-stranded
      oligonucleotides (dsODNs) on polymer modified capillaries. Single base pair (bp)
      resolution (Rs) of dsODNs ranging from 16-20 bp was achieved in free solution on
      an 8 cm capillary dynamically coated with poly(ethylpyrrolidine methacrylate-co
      methyl methacrylate) (PEPyM-co-PMMA) random copolymer. Interestingly, separation
      of a dsODN mixture containing two 16 bp strands of different sequences resulted
      in partial resolution (0.52) implying that the free solution mobility of dsODNs
      was sequence dependent. The single bp resolution achieved for the complementary
      sequence strands (the sequence of all strands in the mixtures contained the same
      16 bp sequence) was improved by up to 37% for separation of dsODNs containing non
      complementary sequences. The 16 bp peak was not additive within each mixture,
      indicating the presence of ODN-ODN interactions. Investigation of these
      interactions (and ODN-buffer interactions) showed that they can be influenced by
      the ionic strength and conductivity of the background electrolyte (BGE).
      Increasing the ionic strength reduced the ODN-ODN interactions and improved the
      resolution, whereas, increasing the conductivity reduced ODN-buffer interactions,
      increasing the mobility, at the consequence of promoting ODN-ODN interactions,
      and hence decreasing the resolution. 

PMID- 24087828
TI  - High temperature synthesis of high silica zeolite Y with good crystallinity in
      the presence of N-methylpyridinium iodide.
AB  - A novel synthetic route is designed, employing both high temperature and a
      nontoxic organic structure-directing agent (SDA), for the synthesis of high
      silica zeolite Y. The N-methylpyridinium used as an organic SDA is stable during
      the synthesis, and the high silica zeolite Y shows high hydrothermal stability
      and good catalytic performance, as well as excellent adsorptive properties. 

PMID- 24087829
TI  - Mitral valve repair versus replacement for moderate-to-severe mitral
      regurgitation in patients undergoing concomitant aortic valve replacement.
AB  - OBJECTIVES: Whether to repair or replace the mitral valve for patients with
      significant mitral regurgitation undergoing aortic valve replacement is still
      controversial. METHODS: From January 1990 to December 2011, a total of 663
      patients underwent aortic valve replacement combined with mitral valve surgery.
      Among these, 253 patients (mean age 55.9 +/- 14.5 years, 91 females) with
      moderate-to-severe mitral regurgitation were enrolled to compare the outcomes
      between double valve replacement (DVR group, n = 158) and aortic valve
      replacement plus mitral valve repair (AVR plus MVr group, n = 95). Survival and
      valve-related events were compared by the inverse-probability-treatment-weighted
      method using propensity scores to reduce treatment selection bias. RESULTS: Early
      mortality was similar between the groups (1.9% in the DVR group when compared
      with 3.2% in the AVR plus MVr group, P = 0.55). During the mean follow-up period
      of 72.1 +/- 56.7 months, 45 patients died (28 in DVR and 17 in AVR plus MVr) and
      31 experienced valve-related events including valve reoperation in 11,
      anticoagulation-related bleeding in 14, thromboembolism complications in 9 and
      infective endocarditis in 3. After adjustment for baseline risk profiles, the DVR
      group showed no difference with regard to risks of death (hazard ratio [HR],
      1.79; 95% confidence interval [CI], 0.79-4.01; P = 0.16) and valve-related events
      (HR, 1.15; 95% CI, 0.40-3.30; P = 0.80) compared with the AVR plus MVr group.
      CONCLUSIONS: Although the outcomes of either mitral valve repair or replacement
      for moderate-to-severe mitral regurgitation in patients undergoing concomitant
      aortic valve replacement show no statistical significance in terms of long-term
      survival and valve-related event rates, DVR seems more hazardous than AVR plus
      MVr based on the estimated HR in terms of survival.

PMID- 24087830
TI  - Does the use of bilateral mammary artery grafts compared with the use of a single
      mammary artery graft offer a long-term survival benefit in patients undergoing
      coronary artery bypass surgery?
AB  - A best evidence topic in cardiac surgery was written according to a structured
      protocol. The question addressed was: 'Does the use of bilateral mammary artery
      grafts compared with the use of a single mammary artery graft offer a long-term
      survival benefit in patients undergoing coronary artery bypass surgery?'
      Altogether 214 papers were found using the reported search, of which 13
      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. All the included
      studies were follow-up studies; eight studies used prospective data collection,
      and five studies collected the study data retrospectively. No randomized
      controlled trials were found. Nine of the 13 included papers used a propensity
      score-matched comparison of the survival of bilateral mammary artery graft [or,
      bilateral internal thoracic artery (BITA) graft] patients vs single mammary
      artery graft [or, single internal thoracic artery (SITA) graft] patients. These
      studies consistently showed an enhanced survival of BITA patients compared with
      propensity-score-matched SITA patients. Three of the 13 included papers used Cox
      proportional hazards regression analysis to compare survival of BITA vs SITA
      patients; one larger study showed better crude survival of BITA patients, but did
      not identify BITA grafts as independent predictor of enhanced survival. The
      remaining two studies also did not identify BITA grafts as independent predictor
      of enhanced survival. One study only presented crude survival estimates of BITA
      vs SITA patients and therefore was of limited informative value. We conclude that
      the use of BITA grafts seems to offer a long-term survival benefit compared with
      a SITA graft for patients undergoing coronary artery bypass grafting surgery.
      Although randomized evidence is lacking, observational evidence supporting this
      hypothesis is mounting. 

PMID- 24087831
TI  - Airtightness of lung parenchyma without a closing suture after atypical resection
      using the Nd:YAG Laser LIMAX 120.
AB  - OBJECTIVES: Lung metastases can be non-anatomically resected with a Nd:YAG Laser.
      It is recommended that the resected lung surface be sealed by slowly resorbable
      sutures. However, the lung tissue may be restricted by the sutures once it is re
      ventilated. Thus, it was analysed whether the lung parenchyma is airtight after
      laser resection without suturing the defect. METHODS: The pulmonary artery of
      unimpaired paracardial lung lobes of freshly slaughtered pigs (mean weight 46 g)
      was cannulated and rinsed out via a hypotonic saline-heparin solution (5000 IE)
      until the perfusate was clear of body fluid. The lobular bronchus was connected
      to an airtight ventilation tube (Fa. VYGON 520 3.5 oral tube) and ventilated
      pressure-controlled (PEEP + 5 cm H2O, P1 = 20 cm H2O, frequency = 10/min) via a
      respirator. All lobes were perfused with Ringer solution at 42 degrees C at
      normothermia and normotonia. In group 1 (n = 8), an atypical peripheral
      parenchymal resection (average resected surface: 2 * 2 cm(2)) and in group 2 (n =
      8), a deep atypical parenchymal resection (average resected surface: 4 * 4 cm(2))
      were performed with the Nd:YAG Laser LIMAX 120 (output power at 100 watts). After
      post-resection ventilation of 15 min, the resection surface was tested for
      airtightness and burst pressure. RESULTS: All group 1 lobes tested airtight under
      pressure-controlled ventilation. The mean burst pressure was 34.4 mbar (SD +/-
      3.2 mbar). Six lobes of group 2 were also completely airtight. The remaining two
      lobes, however, revealed a serious parenchymal leak (score 3). This was caused by
      the cross-opening of a segmental bronchus, although the surrounding lung
      parenchyma was also airtight. The mean burst pressure of these lobes was 31.7
      mbar (SD +/- 4.08 mbar). There was no significant difference between the two
      groups (P = 0.12). CONCLUSIONS: Peripheral lung defects after Nd:YAG Laser
      resection might not be sutured, since the laser-induced vaporization of the lung
      parenchyma seems to be initially airtight. These experimental data warrant
      confirmation in a controlled clinical study.

PMID- 24087832
TI  - Initial experience of pacemaker and implantable cardioverter defibrillator lead
      extraction with the new GlideLight 80 Hz laser sheaths.
AB  - OBJECTIVES: Laser lead extraction is a challenging procedure, especially in
      patients with old or multiple pacemaker (PM) or implantable cardioverter
      defibrillator (ICD) leads. The mechanical force is a leading cause of
      complications during the extraction procedure. Use of new laser sheaths, which
      deliver a rate of 80 pulses per second, may probably reduce intraoperative
      adverse events by reduction of extraction force. METHODS: Between January 2012
      and April 2013, 76 PM and ICD leads were treated in 38 patients using GlideLight
      80 Hz laser sheaths. Indications for lead removals were pocket infection (42.1%),
      septicaemia or endocarditis (23.7%), lead dysfunction (31.6%) and upgrade from PM
      to ICD (2.6%). Data on procedural success rates, intra- and postoperative
      outcomes, as well as 30-day mortality were collected into a database and analysed
      retrospectively. RESULTS: The mean patient age was 62.0 +/- 17.7 years (range 18
      83), and 73.7% were male. The mean time from initial lead implantation was 96.0
      +/- 58.3 months (range 24-288). Thirty-seven (48.7%) PM and 39 (51.3%) ICD leads
      had to be extracted. The mean procedural time was 68.3 +/- 27.3 min (range 35
      115). Seventy-two of 76 leads (94.8%) were completely removed, partial removal
      was achieved in 2 (2.6%) leads and a failure of extraction occurred in 2 (2.6%)
      leads. The overall complication rate was 5.2%, including one major (superior vena
      cava perforation) (2.6%) and one minor (pocket haematoma) (2.6%) complication. No
      death occurred during the 30-day follow-up. CONCLUSIONS: The GlideLight 80 Hz
      laser sheath allows safe and effective removal of chronically implanted PM and
      ICD leads, combining high procedural success with low complication rates.

PMID- 24087833
TI  - Computational characterization of a mechanism for the copper-catalyzed aerobic
      oxidative trifluoromethylation of terminal alkynes.
AB  - A reaction mechanism for the copper(i)-catalyzed oxidative aerobic
      trifluoromethylation of terminal alkynes has been determined by DFT calculations.
      The transmetalation of CF3(-) to copper appears to be a ligand replacement
      process independent of the metal. The dioxygen activation follows the sequence
      eta(1)-superoxocopper(ii), MU-eta(2):eta(2)-peroxodicopper(ii) and bis(MU-oxo)
      dicopper(iii). 

PMID- 24087834
TI  - The sensitivity of Turing self-organization to biological feedback delays: 2D
      models of fish pigmentation.
AB  - Turing morphogen models have been extensively explored in the context of large
      scale self-organization in multicellular biological systems. However, reconciling
      the detailed biology of morphogen dynamics, while accounting for time delays
      associated with gene expression, reveals aberrant behaviours that are not
      consistent with early developmental self-organization, especially the requirement
      for exquisite temporal control. Attempts to reconcile the interpretation of
      Turing's ideas with an increasing understanding of the mechanisms driving
      zebrafish pigmentation suggests that one should reconsider Turing's model in
      terms of pigment cells rather than morphogens (Nakamasu et al., 2009, PNAS, 106:
      , 8429-8434; Yamaguchi et al., 2007, PNAS, 104: , 4790-4793). Here the dynamics
      of pigment cells is subject to response delays implicit in the cell cycle and
      apoptosis. Hence we explore simulations of fish skin patterning, focussing on the
      dynamical influence of gene expression delays in morphogen-based Turing models
      and response delays for cell-based Turing models. We find that reconciling the
      mechanisms driving the behaviour of Turing systems with observations of fish skin
      patterning remains a fundamental challenge. 

PMID- 24087835
TI  - A general synthetic route to [Cu(X)(NHC)] (NHC = N-heterocyclic carbene, X = Cl,
      Br, I) complexes.
AB  - A one-pot procedure for the synthesis of [Cu(X)(NHC)] (X = Cl, Br, I) is
      reported. The reaction is applicable to a wide range of saturated and unsaturated
      NHC ligands, is scalable and proceeds under mild conditions using technical grade
      solvents in air. 

PMID- 24087836
TI  - Palladium-catalyzed direct C-3 oxidative alkenylation of phosphachromones.
AB  - A method for the synthesis of C-3 alkenylated phosphachromones was developed
      using a direct intermolecular C-3 alkenylation with activated and non-activated
      alkenes through C-H activation under aerobic conditions. 

PMID- 24087837
TI  - Antioxidant activity of phenolics in leaves of three red pepper (Capsicum annuum)
      cultivars.
AB  - The antioxidant properties and phenolic profiles were first investigated in this
      paper on the leaves of three red pepper cultivars, Blackcuban (BCPL), Hongjinju
      (HPL), and Yeokgang-hongjanggun (YHPL). Of the ethanol extract of the three
      cultivars, BCPL showed potent antioxidant activities against the 1,1-diphenyl-2
      picrylhydrazyl radical (DPPH) and the 2,2-azinobis(3-ethylbenzothiazoline-6
      sulfonic acid) (ABTS) radical. Nine antioxidative compounds from the red pepper
      leaves were isolated and identified as one polyamine phenolic conjugate, N
      caffeoylputrescine (1); three chlorogenic acid derivatives, 5-O-caffeoylquinic
      acid (2), 5-O-caffeoylquinic acid methyl ester (4), and 5-O-caffeoylquinic acid
      butyl ester (9); one anthocyanin, delphinidin-3-[4-trans-coumaroyl-l-rhamnosyl(1
      >6)glucopyranoside]-5-O-glucopyranoside (3); and four flavone glycosides,
      luteolin-7-O-apiofuranosyl(1->2)glucopyranoside (5), luteolin-7-O-glucopyranoside
      (6), apigenin 7-O-apiofuranosyl(1->2)glucopyranoside (7), apigenin-7-O
      glucopyranoside (8). 1 and 3 had the greatest potential for radical-scavenging
      activity and HepG2 cells protecting effect against oxidative stress. BCPL
      exhibited the highest content of 1 and 3. Of the three cultivars BCPL may be
      considered a good source of antioxidants. 

PMID- 24087839
TI  - Lymphocyte depleted Hodgkin lymphoma with common variable immunodeficiency.

PMID- 24087840
TI  - Avascular necrosis of femoral head as the initial manifestation of CML.
AB  - A 12-year-old female is reported who presented with right hip pain for 6 months.
      With massive splenohepatomegaly and leukocytosis, CML was suspected and confirmed
      on bone-marrow examination and cytogenetics. Further investigations confirmed
      avascular necrosis (AVN) of the right femoral head. CML was treated by
      hydroxyurea, followed by imatinib. AVN was managed conservatively; patient
      demonstrated progressive improvement, though a mild limp in the gait was
      persisting at 22 months. AVN as the initial manifestation of CML is a rarity.
      Leukostasis is considered to be the pathophysiological mechanism. In view of the
      rarity, a case is reported, along with compilation of previously reported cases.

PMID- 24087838
TI  - How conformational flexibility stabilizes the hyperthermophilic elongation factor
      G-domain.
AB  - Proteins from thermophilic organisms are stable and functional well above ambient
      temperature. Understanding the molecular mechanism underlying such a resistance
      is of crucial interest for many technological applications. For some time,
      thermal stability has been assumed to correlate with high mechanical rigidity of
      the protein matrix. In this work we address this common belief by carefully
      studying a pair of homologous G-domain proteins, with their melting temperatures
      differing by 40 K. To probe the thermal-stability content of the two proteins we
      use extensive simulations covering the microsecond time range and employ several
      different indicators to assess the salient features of the conformational
      landscape and the role of internal fluctuations at ambient condition. At the
      atomistic level, while the magnitude of fluctuations is comparable, the
      distribution of flexible and rigid stretches of amino-acids is more regular in
      the thermophilic protein causing a cage-like correlation of amplitudes along the
      sequence. This caging effect is suggested to favor stability at high T by
      confining the mechanical excitations. Moreover, it is found that the thermophilic
      protein, when folded, visits a higher number of conformational substates than the
      mesophilic homologue. The entropy associated with the occupation of the different
      substates and the thermal resilience of the protein intrinsic compressibility
      provide a qualitative insight on the thermal stability of the thermophilic
      protein as compared to its mesophilic homologue. Our findings potentially open
      the route to new strategies in the design of thermostable proteins. 

PMID- 24087841
TI  - Density functional theory mechanistic study of the reduction of CO2 to CH4
      catalyzed by an ammonium hydridoborate ion pair: CO2 activation via formation of
      a formic acid entity.
AB  - Density functional theory computations have been applied to gain insight into the
      CO2 reduction to CH4 with Et3SiH, catalyzed by ammonium hydridoborate 1
      ([TMPH](+)[HB(C6F5)3](-), where TMP = 2,2,6,6-tetramethylpiperidine) and
      B(C6F5)3. The study shows that CO2 is activated through the concerted transfer of
      H(delta+) and H(delta-) of 1 to CO2, giving a complex (IM2) with a well-formed
      HCOOH entity, followed by breaking of the O-H bond of the HCOOH entity to return
      H(delta+) to TMP, resulting in an intermediate 2 ([TMPH](+)[HC(?O)OB(C6F5)3)](
      )), with CO2 being inserted into the B-H bond of 1. However, unlike CO2 insertion
      into transition-metal hydrides, the direct insertion of CO2 into the B-H bond of
      1 is inoperative. The computed CO2 activation mechanism agrees with the
      experimental synthesis of 2 via reacting HCOOH with TMP/B(C6F5)3. Subsequent to
      the CO2 activation and B(C6F5)3-mediated hydrosilylation of 2 to regenerate the
      catalyst (1), giving HC(?O)OSiEt3 (5), three hydride-transfer steps take place,
      sequentially transferring H(delta-) of Et3SiH to 5 to (Et3SiO)2CH2 (6, the
      product of the first hydride-transfer step) to Et3SiOCH3 (7, the product of the
      second hydride-transfer step) and finally resulting in CH4. These hydride
      transfers are mediated by B(C6F5)3 via two SN2 processes without involving 1.
      B(C6F5)3 acts as a hydride carrier that, with the assistance of a nucleophilic
      attack of 5-7, first grabs H(delta-) from Et3SiH (the first SN2 process), giving
      HB(C6F5)3(-), and then leave H(delta-) of HB(C6F5)3(-) to the electrophilic C
      center of 5-7 (the second SN2 process). The SN2 processes utilize the
      electrophilic and nucleophilic characteristics possessed by the hydride acceptors
      (5-7). The hydride-transfer mechanism is different from that in the CO2 reduction
      to methanol catalyzed by N-heterocyclic carbene (NHC) and PCP-pincer nickel
      hydride ([Ni]H), where the characteristic of possessing a C?O double bond of the
      hydride acceptors is utilized for hydride transfer. The mechanistic differences
      elucidate why the present system can completely reduce CO2 to CH4, whereas NHC
      and [Ni]H catalysts can only mediate the reduction of CO2 to [Si]OCH3 and
      catBOCH3, respectively. Understanding this could help in the development of
      catalysts for selective CO2 reduction to CH4 or methanol. 

PMID- 24087842
TI  - Towards a physiological signal-based access solution for a non-verbal adolescent
      with severe and multiple disabilities.
AB  - OBJECTIVE: To find physiologically arousing stimuli and labile physiological
      channels in a non-verbal adolescent with severe and multiple congenital
      disabilities, who did not have a reliable means of communication. METHODS: The
      client was repeatedly presented with visual and audiovisual stimuli, representing
      variations of six contextual factors over three sessions in a one month period.
      For each stimulus, reactions were detected in the client's four peripheral
      autonomic nervous system signals using a rule-based classification algorithm.
      RESULTS: During the presentation of audiovisual stimuli, the number of
      physiological reactions significantly differed from that observed in baseline
      (chi(2) = 3.93, p = 0.0476). Aural stimuli articulated in an unfamiliar voice,
      and aural stimuli containing anticipatory patterns were also physiologically
      arousing. Fingertip temperature was the client's most labile physiological
      signal. CONCLUSIONS: The results of this case study suggest that physiological
      data may complement caregiver acumen in deciphering the reactions of non-verbal
      clients with severe and multiple disabilities.

PMID- 24087843
TI  - Exploring the effects of isothiocyanates on chemotherapeutic drugs.
AB  - INTRODUCTION: Chemoprevention has emerged as a promising strategy to reduce the
      risk and to control cancer. In this context, isothiocyanates (ITCs), found in
      abundance in the form of glucosinolates in cruciferous vegetables, have gained
      increasing consideration for their chemopreventive activity. ITCs exert their
      effects mainly by inducing carcinogen metabolism or by inhibiting tumor cell
      proliferation. AREAS COVERED: In recent years, novel combination treatments, by
      coupling chemopreventive agents and typical chemotherapeutics, have been
      exploited to increase the antitumor activities. The aim of this article is to
      examine the foremost studies carried out, so far, on the effects of dietary and
      synthetic ITCs on different signaling pathways involved in the pharmacokinetics
      and pharmacodynamics of chemotherapeutic agents, in order to enhance their
      effectiveness. EXPERT OPINION: Undoubtedly, the beneficial anticarcinogenic
      potential of ITCs, both singly and in combination, has emerged in in vitro and in
      vivo studies. However, only a few clinical trials have been carried out so far
      with ITCs, which try to better define both the pharmacokinetic and
      pharmacodynamic impacts in humans. More toxicological evaluations after long-term
      administration of ITCs in different species are required for the clinical
      development of ITCs as anticarcinogenic agents.

PMID- 24087844
TI  - Detection of intestinal intraepithelial lymphocytes, goblet cells and secretory
      IgA in the intestinal mucosa during Newcastle disease virus infection.
AB  - Newcastle disease, which is caused by Newcastle disease virus (NDV), is a highly
      contagious viral disease of poultry and other bird species. The mucosa is the
      first line of defence to invading pathogens, including NDV, and it has been
      confirmed that the mucosa can contribute to host protection. This study was
      conducted to evaluate the intestinal mucosal immunology in NDV infection. Forty
      specific-pathogen-free chickens were divided into two groups, 20 birds in each
      group. Group 1 was inoculated with NDV by the intravenous route. Group 2 was used
      as the control group and was given sterile phosphate-buffered saline by the same
      route. At 24, 48, 72, and 96 h post infection (h.p.i.), five chickens from each
      treatment were killed. Samples of the duodenum, jejunum, and ileum were collected
      to quantify intestinal intraepithelial lymphocytes (IEL), goblet cells and
      secretory IgA (sIgA) by cytochemistry and immunohistochemistry analysis. The
      results indicated that IEL were increased from 24 to 72 h.p.i. in the infected
      tissues, and were significantly higher than in the control group at 48 h.p.i. (P
      < 0.01). In contrast to IEL, goblet cell numbers were reduced dramatically from
      24 to 96 h.p.i. in the infected birds (P < 0.01) Furthermore, the content of sIgA
      was significantly higher at 48 and 72 h.p.i. in the infected tissues (P < 0.01).
      sIgA positivity was observed in the epithelial lining of the intestinal mucosa.
      These data suggest that IEL, goblet cells, and sIgA were involved in the
      intestinal mucosal immunity against NDV infection. 

PMID- 24087846
TI  - The effect of celecoxib administration on the healing and neovascularization of
      colonic anastomosis in rats.
AB  - BACKGROUND: The aim of this experimental study was to investigate whether the
      perioperative administration of the selective cyclooxygenase-2 inhibitor
      celecoxib affects the angiogenetic process and the healing of colonic
      anastomoses. METHODS: Seventy-two male Wistar rats underwent colonic resection
      and anastomosis. Celecoxib (10 mg/kg/day-celecoxib group) or placebo (control
      group) was administered perioperatively. Rats of both groups were sacrificed on
      either the third or the seventh postoperative day and bursting pressures of the
      anastomoses were measured. Gelatine-degrading matrix metalloproteinases (MMPs)
      were identified with gelatine zymography, and proMMP-2 and vascular endothelial
      growth factor (VEGF) levels from both anastomotic site and tissue adjacent to the
      anastomosis were evaluated. Histologic evaluation of microvessels was performed
      by immunohistochemistry using an anti-CD34 monoclonal antibody. RESULTS:
      Celecoxib did not significantly decrease anastomotic bursting pressures. Gelatin
      zymography revealed the presence of MMP-2, proMMP-2, and proMMP-9. MMP
      concentration was higher at the anastomotic tissue as compared with tissue
      distant to the anastomosis. Celecoxib resulted in a significant reduction in
      proMMP-2 levels at the anastomosis at both third and seventh postoperative day.
      VEGF levels from the anastomotic tissue were also found lower in the celecoxib
      group. Histological examination showed a celecoxib-induced reduction of newly
      formed CD34-stained vessels. CONCLUSIONS: Although the perioperative
      administration of celecoxib resulted in suppression of angiogenesis in the newly
      formed anastomoses, bursting pressures remained unaffected and subsequently
      safety was not compromised.

PMID- 24087847
TI  - Matrix-assisted laser desorption ionization mass spectrometry imaging for peptide
      and protein analyses: a critical review of on-tissue digestion.
AB  - Matrix-assisted laser desorption/ionization mass spectrometry imaging (MALDI-MSI)
      has established itself among the plethora of mass spectrometry applications. In
      the biomedical field, MALDI-MSI is being more frequently recognized as a new
      method for the discovery of biomarkers and targets of treatment, classification
      of diseased and healthy tissues, or prediction of the outcome of a pathology. The
      technology has been used to study the localization of proteolytic peptides
      directly on tissue sections. A direct correlation between the detected peptides
      and the distribution and identity of the original precursor protein is the
      ultimate goal of any MALDI-MSI experiment. Enzymatic digestion protocols are
      commonly used to reveal the protein signature of these complex tissues.
      Considerations that pertain to methods of sample preparation, on-tissue
      digestion, data analysis, and visualization will be addressed. This review will
      also discuss selected applications of on-tissue digestion combined with the MALDI
      MSI technology in biomedicine. 

PMID- 24087848
TI  - Interplay of charge state, lability, and magnetism in the molecule-like
      Au25(SR)18 cluster.
AB  - Au25(SR)18 (R = -CH2-CH2-Ph) is a molecule-like nanocluster displaying distinct
      electrochemical and optical features. Although it is often taken as an example of
      a particularly well-understood cluster, very recent literature has provided a
      quite unclear or even a controversial description of its properties. We prepared
      monodisperse Au25(SR)18(0) and studied by cyclic voltammetry, under particularly
      controlled conditions, the kinetics of its reduction or oxidation to a series of
      charge states, -2, -1, +1, +2, and +3. For each electrode process, we determined
      the standard heterogeneous electron-transfer (ET) rate constants and the
      reorganization energies. The latter points to a relatively large inner
      reorganization. Reduction to form Au25(SR)18(2-) and oxidation to form
      Au25(SR)18(2+) and Au25(SR)18(3+) are chemically irreversible. The corresponding
      decay rate constants and lifetimes are incompatible with interpretations of very
      recent literature reports. The problem of how ET affects the Au25 magnetism was
      addressed by comparing the continuous-wave electron paramagnetic resonance (cw
      EPR) behaviors of radical Au25(SR)18(0) and its oxidation product, Au25(SR)18(+).
      As opposed to recent experimental and computational results, our study provides
      compelling evidence that the latter is a diamagnetic species. The DFT-computed
      optical absorption spectra and density of states of the -1, 0, and +1 charge
      states nicely reproduced the experimentally estimated dependence of the HOMO-LUMO
      energy gap on the actual charge carried by the cluster. The conclusions about the
      magnetism of the 0 and +1 charge states were also reproduced, stressing that the
      three HOMOs are not virtually degenerate as routinely assumed: In particular, the
      splitting of the HOMO manifold in the cation species is severe, suggesting that
      the usefulness of the superatom interpretation is limited. The electrochemical,
      EPR, and computational results thus provide a self-consistent picture of the
      properties of Au25(SR)18 as a function of its charge state and may furnish a
      methodology blueprint for understanding the redox and magnetic behaviors of
      similar molecule-like gold nanoclusters. 

PMID- 24087849
TI  - Effects of consumptive water use on biodiversity in wetlands of international
      importance.
AB  - Wetlands are complex ecosystems that harbor a large diversity of species.
      Wetlands are among the most threatened ecosystems on our planet, due to human
      influences such as conversion and drainage. We assessed impacts from water
      consumption on the species richness of waterbirds, nonresidential birds, water
      dependent mammals, reptiles and amphibians in wetlands, considering a larger
      number of taxa than previous life cycle impact assessment methods. Effect factors
      (EF) were derived for 1184 wetlands of international importance. EFs quantify the
      number of global species-equivalents lost per m(2) of wetland area loss.
      Vulnerability and range size of species were included to reflect conservation
      values. Further, we derived spatially explicit characterization factors (CFs)
      that distinguish between surface water and groundwater consumption. All relevant
      watershed areas that are contributing to feeding the respective wetlands were
      determined for CF applications. In an example of rose production, we compared
      damages of water consumption in Kenya and The Netherlands. In both cases, the
      impact was largest for waterbirds. The total impact from water consumption in
      Kenya was 67 times larger than in The Netherlands, due to larger species richness
      and species' vulnerability in Kenya, as well as more arid conditions and larger
      amounts of water consumed. 

PMID- 24087850
TI  - Kinetics of allosteric transitions in S-adenosylmethionine riboswitch are
      accurately predicted from the folding landscape.
AB  - Riboswitches are RNA elements that allosterically regulate gene expression by
      binding cellular metabolites. The SAM-III riboswitch, one of several classes that
      binds S-adenosylmethionine (SAM), represses translation upon binding SAM (OFF
      state) by encrypting the ribosome binding sequence. We have carried out
      simulations of the RNA by applying mechanical force (f) to the ends of SAM-III,
      with and without SAM, to get quantitative insights into the f-dependent
      structural changes. Force-extension (z) curves (FECs) for the apo (ON) state,
      obtained in simulations in which f is increased at a constant loading rate, show
      three intermediates, with the first one being the rupture of SAM binding region,
      which is greatly stabilized in the OFF state. Force-dependent free energy
      profiles, G(z,f), as a function of z, obtained in equilibrium constant force
      simulations, reveal the intermediates observed in FECs. The predicted stability
      difference between the ON and OFF states using G(z,f) is in excellent agreement
      with experiments. Remarkably, using G(z,f)s and estimate of an effective
      diffusion constant at a single value of f allows us to predict the f-dependent
      transition rates using theory of first passage times for both the apo and holo
      states. To resolve the kinetics of assembly of SAM-III riboswitch in structural
      terms, we use force stretch-quench pulse sequences in which the force on RNA is
      maintained at a low (fq) value starting from a high value for a time period tq.
      Variation of tq over a wide range results in resolution of elusive states
      involved in the SAM binding pocket and leads to accurate determination of folding
      times down to fq = 0. Quantitative measure of the folding kinetics, obtained from
      the folding landscape, allows us to propose that, in contrast to riboswitches
      regulating transcription, SAM-III functions under thermodynamic control provided
      the basal concentration of SAM exceeds a small critical value. All of the
      predictions are amenable to tests in single molecule pulling experiments. 

PMID- 24087851
TI  - Ni-catalyzed reductive homocoupling of unactivated alkyl bromides at room
      temperature and its synthetic application.
AB  - A room-temperature Ni-catalyzed reductive approach to homocoupling of unactivated
      primary, secondary, and tertiary alkyl bromides is described. The catalytic
      system can be easily generated from air-stable and cheap materials and
      demonstrates broad functional group tolerance, thus allowing facile access to
      useful dimeric triterpene and lignan-like molecules. Moreover, the dimerization
      of tertiary bromide 6 efficiently establishes sterically hindered vicinal
      quaternary carbons (C3a and C3a'), which is a key linkage of intriguing
      bispyrrolo[2,3-b]indoline alkaloids, thereby enabling us to complete the total
      syntheses of racemic chimonanthine (9) and folicanthine (10). In addition, this
      dimerization method can be expanded to the highly stereoselective synthesis of
      bisperhydrofuro[2,3-b]furan (5a) and the dimeric spiroketal 5b, signifying the
      involvement of possible radical species. 

PMID- 24087852
TI  - Timing of intrathecal baclofen therapy in persons with acquired brain injury:
      influence on outcome.
AB  - OBJECTIVE: Evaluation of the effects of intrathecal baclofen therapy (ITB)
      delivered by a pump implanted at a very early stage in acquired brain injury
      (ABI). STUDY DESIGN: This investigation was a longitudinal prospective
      observational study, including a series of 13 ABI implanted within 6 months of
      the acute events. MAIN OUTCOME MEASURE: The Modified Ashworth Scale (MAS) and
      Spasms Frequency Score (SFS) have been used as a primary outcome measure. The
      Disability Rating Scale (DRS) and Level of Cognitive Functioning (LCF) scores
      have been computed in order to verify possible interferences of baclofen therapy
      at an early stage on a global outcome. An intrathecal bolus test was not
      performed. Drug tolerability was tested by oral administration of baclofen 100
      mg. RESULTS: Reduction of spasticity and spasms frequency were measured 3 months
      after patients received the implant and at the 1-year follow-up. There was no
      difference found for global outcome measure between the group of patients who
      received the implant earlier (within 3 months) compared to the group who received
      it later (between 3-6 months). CONCLUSION: ITB therapy in ABI should be
      considered as early as possible. The implants are safe and effective in reducing
      spasticity. An intrathecal bolus test was not compulsory in ABI.

PMID- 24087853
TI  - Brain pharmacokinetics of neurotoxin-loaded PLA nanoparticles modified with
      chitosan after intranasal administration in awake rats.
AB  - CONTEXT: Neurotoxin (NT), an analgesic peptide which was separated from the venom
      of Naja naja atra, is endowed an exceptional specificity of action that blocks
      transmission of the nerve impulse by binding to the acetylcholine receptor in the
      membrane. However, it has limited permeability across the blood-brain barrier
      (BBB). OBJECTIVE: The purpose of this study was to encapsulate NT within
      polylactic acid (PLA) nanoparticles (NPs) modified with chitosan (NT-PLA-cNPs)
      and to evaluate their brain pharmacokinetic behaviors after intranasal (i.n.)
      administration using a microdialysis technique in free-moving rats. METHODS: NT
      PLA-cNPs (NT labeled with fluorescein isothiocyanate) were prepared and
      characterized. Then, NT-PLA-cNPs were i.n. administered to rats and the
      fluorescence intensity in the periaqueductal gray (PAG) was monitored for up to
      480 min, with NT-PLA-NPs and NT solution as control groups. RESULTS: The NPs
      prepared were spherical with a homogenous size distribution. The mean particle
      size, zeta potential, and entrapment efficiency were 140.5 +/- 5.4 nm, +33.71 +/-
      3.24 mV, and 83.51 +/- 2.65%, respectively. The brain transport results showed
      that Tmax of NT-PLA-cNPs was equal with that of NT-PLA-NPs after i.n.
      administration (150 min). The Cmax and AUC(0-8 h) of each group followed the
      following order: NT-PLA-cNPs > NT-PLA-NPs. The corresponding absolute
      bioavailability (Fabs) of NT-PLA-cNPs was about 151% with NT-PLA-NPs as reference
      preparations. CONCLUSION: These results suggest that NPs modified with chitosan
      have better brain targeting efficiency and are a promising approach for i.n.
      delivery of large hydrophilic peptides and proteins in improving the treatment of
      central nervous system (CNS) disorders.

PMID- 24087854
TI  - The effect of ethanol on the formation and physico-chemical properties of
      particles generated from budesonide solution-based pressurized metered-dose
      inhalers.
AB  - The aerosol performance of budesonide solution-based pressurized metered-dose
      inhalers (HFA 134a), with various amounts of ethanol (5-30%, w/w) as co-solvents,
      was evaluated using impaction and laser diffraction techniques. With the increase
      of ethanol concentration in a formulation, the mass median aerodynamic diameter
      was increased and the fine particle fraction showed a significant decline.
      Although data obtained from laser diffraction oversized that of the impaction
      measurements, good correlations were established between the two sets of data.
      Particles emitted from all the five formulations in this study were amorphous,
      with two different types of morphology - the majority had a smooth surface with a
      solid core and the others were internally porous with coral-like surface
      morphology. The addition of ethanol in the formulation decreased the percentage
      of such irregular-shape particles from 52% to 2.5% approximately, when the
      ethanol concentration was increased from 5% to 30%, respectively. A hypothesis
      regarding the possible particle formation mechanisms was also established. Due to
      the difference of droplet composition from the designed formulation during the
      atomization process, the two types of particle may have gone through distinct
      drying processes: both droplets will have a very short period of co-evaporation,
      droplets with less ethanol may be dried during such period; while the droplets
      containing more ethanol will undergo an extra condensation stage before the final
      particle formation. 

PMID- 24087855
TI  - Dissolution enhancement of cefdinir with hydroxypropyl-beta-cyclodextrin.
AB  - The solid state properties and dissolution behavior of binary systems of cefdinir
      (CEF) with hydroxypropyl-beta-cyclodextrin (HP-beta-CD) were investigated. CEF-HP
      beta-CD interaction in the solution state was studied by phase-solubility
      analysis and demonstrates the ability of HP-beta-CD to complex with CEF giving
      A(L) type profile with 65.28 +/- 1.3 M-1 stability constant. The freeze drying
      technique was adopted to prepare binary systems of CEF with HP-beta-CD in 1:1
      molar ratio. The solid inclusion was characterized by fourier transform infrared
      spectroscopy (FTIR), differential scanning calorimetry (DSC), X-ray powder
      diffractometry (XRD), and scanning electron microscopy (SEM). Aqueous solubility
      of CEF-HP-beta-CD inclusion complex was 2.36-fold of pure CEF. The dissolution
      profiles of inclusion complexes were determined and compared with those of CEF
      alone and their physical mixtures. The dissolution rate of inclusion complex was
      superior than the CEF alone. These approaches indicated that CEF was able to form
      an inclusion complex with HP-beta-CD, and the inclusion compounds exhibited
      different spectroscopic features and properties.

PMID- 24087856
TI  - Study of the properties of the new biodegradable polyurethane PU (TEG-HMDI) as
      matrix forming excipient for controlled drug delivery.
AB  - The purpose of this work is to study the ability of a new biodegradable
      polyurethane PU(TEG-HMDI) obtained by reaction of triethylene glycol (TEG) with
      1,6-hexamethylene diisocyanate (HMDI) to act as matrix forming polymer for
      controlled release tablets and to estimate its percolation threshold in a matrix
      system. Matrix tablets weighing 250 mg were prepared by direct compression with
      10-30% wt/wt of PU(TEG-HMDI) and anhydrous theophylline as model drug. Release
      studies were carried out using the paddle method. The results were analyzed using
      the kinetics models of Higuchi, Korsmeyer-Peppas, and Peppas and Sahlin. These
      studies confirm the existence of an excipient percolation threshold between 10
      and 20 % wt/wt of PU(TEG-HMDI) for the different batches prepared. It has been
      observed that the new biodegradable polyurethane PU(TEG-HMDI) shows adequate
      compatibility as well as a high ability to control the drug release.

PMID- 24087858
TI  - Tandem isomerization and C-H activation: regioselective hydroheteroarylation of
      allylarenes.
AB  - The first Ni-promoted prototype reaction based on the tandem C-H activation of
      heteroarenes with alkene isomerization is demonstrated, leading to the branched
      hydroheteroarylation products. Simultaneously, the reaction selectivity can be
      chemically switched to linear adducts through Ni-Al tandem catalysis. 

PMID- 24087857
TI  - The bat flower: a source of microtubule-destabilizing and -stabilizing compounds
      with synergistic antiproliferative actions.
AB  - The biosynthesis of secondary metabolites provides higher plants with mechanisms
      of defense against microbes, insects, and herbivores. One common cellular target
      of these molecules is the highly conserved microtubule cytoskeleton, and
      microtubule-targeting compounds with insecticidal, antifungal, nematicidal, and
      anticancer activities have been identified from plants. A new retro
      dihydrochalcone, taccabulin A, with microtubule-destabilizing activity has been
      identified from the roots and rhizomes of Tacca species. This finding is notable
      because the microtubule-stabilizing taccalonolides are also isolated from these
      sources. This is the first report of an organism producing compounds with both
      microtubule-stabilizing and -destabilizing activities. A two-step chemical
      synthesis of taccabulin A was performed. Mechanistic studies showed that
      taccabulin A binds within the colchicine site on tubulin and has synergistic
      antiproliferative effects against cancer cells when combined with a
      taccalonolide, which binds to a different site on tubulin. Taccabulin A is
      effective in cells that are resistant to many other plant-derived compounds. The
      discovery of a natural source that contains both microtubule-stabilizing and 
      destabilizing small molecules is unprecedented and suggests that the synergistic
      action of these compounds was exploited by nature long before it was discovered
      in the laboratory. 

PMID- 24087859
TI  - Patient safety incident prevention and management among Finnish dentists.
AB  - OBJECTIVE: Assessing current patient safety incident (PSI) prevention measures
      and risk management practices among Finnish dentists. MATERIALS AND METHODS: A
      total of 1041 dentists practicing in the private or public sectors in southern
      Finland completed an online questionnaire concerning PSI prevention, PSI
      reporting systems, feedback and knowledge gained from device incidents and
      patient-generated safety information and the knowledge of national PS-guidance.
      The answers were handled anonymously. Statistical evaluations were performed
      using chi-square analysis. RESULTS: Dentists suggested multiple methods for
      preventing PSIs related to dental diagnostics, various treatments, equipment and
      devices, medications, communication, infection control and general practice
      safety. Preventive methods reported most frequently included working with caution
      and forethought, keeping accurate patient records and the availability of correct
      patient information. A special PSI-reporting system was used by less than one
      third of respondents. Feedback received on PS-related data and the utilization of
      guidebooks varied significantly between the studied dentist groups. CONCLUSIONS:
      Several PSI prevention techniques are already used in Finland. However, wide
      variation exists in PSI prevention and risk management practices among Finnish
      dentists. Systematic implementation of available safety methods would probably
      prevent several PSIs. The results indicate that the more dentists know about PS
      risks, the easier it is for them to recognize situations possibly leading to
      patient harm. Anonymous PSI reports, patient complaints and claims data should,
      therefore, be actively used for mutual learning. Increased PS education in
      dentistry is also needed.

PMID- 24087860
TI  - A new monoterpene glycoside from Siparuna thecaphora.
AB  - Phytochemical investigation of the extracts of the leaves of Siparuna thecaphora
      (Poepp. et Endl.) A. DC. (Siparunaceae) allowed the isolation of one monoterpene
      glycoside, named trans-thujane-1alpha,7-diol 1-O-beta-D-glucopyranoside (1) along
      with rutin, quercetin 3-O-beta-D-glucopyranoside and 3,4-dihydroxybenzaldehyde.
      Their structural characterisation was obtained on the basis of extensive
      spectroscopic analyses, including 1D and 2D NMR experiments and HR-ESI-MS.

PMID- 24087861
TI  - Foreword.

PMID- 24087863
TI  - Chapter 1. Introduction: using narrative research methods for the analysis of use
      and misuse of alcohol and drugs.

PMID- 24087864
TI  - Chapter 2. General theoretical perspectives of narrative analysis of substance
      use-related dependency.
AB  - This chapter provides a short introduction to, and an overview for, using
      narrative analysis in the understanding of the use and misuse of alcohol and
      drugs. Important theoretical and methodological dimensions are discussed. Some
      tentative conclusions, limitations, and unresolved critical issues concerning the
      use of narrative research methods in the analysis of substance use-related
      dependency problems are also presented. 

PMID- 24087865
TI  - Chapter 3. A multidimensional model for narrative analysis of substance use
      related dependency.
AB  - This chapter examines the possibilities and limitations of using a narrative
      method as a framework within a multidimensional model for exploring and analyzing
      the use and misuse of alcohol and drugs. It is posited that a multidimensional
      model, based on narrative reasoning, can give a more detailed and specific
      understanding of substance users, who represent a heterogeneous population of
      people, and of substance use-related dependency problems. Such a model describes
      and analyses the drug-use related problems in a manner that provides holistic and
      important information and knowledge about the person by contextual and situation
      interaction processes which are involved in the use/misuse of alcohol and drugs.
      Tentative conclusions and unresolved critical issues are considered. 

PMID- 24087866
TI  - Chapter 4. A self-theoretical perspective on the use-misuse of alcohol and drugs
      based on qualitative and narrative data.
AB  - This article discusses different self-theoretical perspectives of the self that
      are of importance in the analysis of the use and misuse of alcohol and
      psychoactive drugs. The self-theories considered here include cognitive,
      psychodynamic, transpersonal, and social constructivist perspectives. A
      multidimensional perspective focusing on the connection between identity
      structures and analyzing the use/misuse of alcohol and psychoactive drugs is
      presented. The article argues for a self-theoretical analysis based on narrative
      data in order to reach an in-depth understanding of the use and misuse of alcohol
      and psychoactive drugs. 

PMID- 24087867
TI  - Chapter 5. Russian media narratives about young drug users.
AB  - Since the 1960s, the media in Western Europe and the United States has been one
      important actor in the public understanding of the drug phenomenon. In Russia,
      however, it is only since the 1980s that illegal drugs have been discussed in the
      media and this discussion remains on-going today. By using narrative analysis,
      this article focuses on how illegal drug use among young people is constructed in
      the Russian press. As a result of the narrative analysis, three main discourses
      were identified: a foreign problem discourse, a disease discourse, and a medical
      discourse. 

PMID- 24087868
TI  - Chapter 6. The new story: on the possibility of liberating oneself from the drug
      self.
AB  - This chapter explores the meaning(s) of "treatment effect" within the
      psychodynamic tradition. The conventional wisdom is that a successful treatment
      presupposes a transformation of unconscious "material" to a conscious level. The
      "treatment effect" is reinterpreted as being better understood as changing an old
      (and detrimental) story into a new tale-an alternative narrative about the self.
      New possibilities following this conceptual change are introduced with the aid of
      some concrete examples. 

PMID- 24087869
TI  - Chapter 7. Narrative stories and discourses in an interview with a former
      amphetamine user.
AB  - This study analyzes how an individual constructs his life as a former amphetamine
      user. The study has a methodological purpose, providing an example of how
      narrative analysis and discourse analysis can be conducted and combined. First,
      an interview with a former amphetamine user in his 50s was analyzed by the
      narrative method with a focus on identity construction. Second, it was then
      examined from a discourse analytical perspective. The article demonstrates how
      discourse analysis and narrative analysis could be combined when analyzing
      identity constructions. 

PMID- 24087870
TI  - Chapter 8. An indigenous narrative of resilience: Malama ko Aloha.
AB  - Many indigenous cultures use storytelling as the foundation for the transmission
      of important cultural information. Stories passed down from generation to
      generation sometimes teach, record history, provide examples, or inform. One
      important function of storytelling is the transmission of stories about cultural
      resilience illustrating how a cultural group has kept strong in the face of
      adversity. This article shows how storytelling in the Hawaiian culture has been
      used for this purpose and how the Beamer family has served as the master
      storytellers of their culture, keeping the culture and traditions alive through
      their music, dance, and stories. 

PMID- 24087871
TI  - Chapter 9. Drug user researchers as autoethnographers: "doing reflexivity" with
      women drug users.
AB  - This article explores autoethnography, based upon transcribed, narratives,
      conversations, and research notes, as a useful method of creating social and
      cultural insights into the lives of women drug users and their particular kinds
      of problems and to related issues of reflexivity, reliability, and validity. A
      critical issue is raised by asking the question "where do we go from here?"
      contending that we must challenge outdated methodological traditions and canons
      that deny autoethnographers their voice and close the door to their claims of
      authenticity. 

PMID- 24087872
TI  - Chapter 10. Perspectives on treatment, alliance and narratives concerning
      substance use-related dependency.
AB  - This article considers different perspectives on the treatment of substance use
      related dependency, focusing on the importance of a therapeutic relationship,
      working alliance, counseling, and the use of narrative methods. The article also
      discusses some unresolved critical issues concerning the possibilities and
      limitations of acquiring necessary knowledge about substance use-related
      dependency when using narrative research methods. The main conclusion is that the
      therapeutic relationship between the therapist and the client is of crucial
      importance for a positive outcome of treatment and that narrative methods provide
      a detailed empirical database for analyses of substance use-related dependency. 

PMID- 24087873
TI  - Chapter 11. Narratives of clients' experiences of drug use and treatment of
      substance use-related dependency.
AB  - The article focuses on narratives of clients' experiences of using/misusing
      alcohol and drugs and includes comments on their therapeutic process during
      treatment for dependency on psychoactive drugs. It discusses the role of
      narratives that focus on clients' experiences of understanding the use/misuse of
      psychoactive drugs, emphasizing the importance of the narratives. Narrative
      therapy for substance-use-related dependency is discussed. Insight into the
      treatment processes of dependency, based on narrative case illustrations, is also
      provided. 

PMID- 24087874
TI  - Chapter 12. Therapists' narratives of therapeutic relationships in the treatment
      of drug-dependent patients.
AB  - The article explores and analyzes therapists' narratives, using selected stories,
      and their strategies for achieving a positive therapeutic relationship and a
      therapeutic alliance with their patients as a critical dimension to enable
      effective treatment with patients manifesting dependency problems. Although the
      therapists are applying different treatment and dependency theories and methods
      they all emphasize the importance of the therapeutic alliance in order to be
      successful in the treatment process. 

PMID- 24087875
TI  - Chapter 13. Using narrative therapy with Native American recreational tobacco
      users.
AB  - This article describes a technique for helping recreational tobacco-using Native
      American clients change their smoking lifestyle. The technique is based in social
      work practice with a specific focus on the use of narrative therapy. The
      foundation of narrative therapy can be used across ethnicities for smoking
      related issues. Finally, we propose the use of a clinical instrument, called the
      Success Journal, for practitioner use. 

PMID- 24087876
TI  - Chapter 14. Discussion about narrative methods as a strategy for investigating
      and understanding the use and misuse of alcohol and drugs.
AB  - Preliminary and tentative conclusions concerning theoretical and methodological
      issues about narrative methods and their use as a research strategy for
      investigating and understanding the use and misuse of alcohol and drugs are
      presented. The treatment methods that are influenced by narrative strategies as
      well as this tool's limitations are noted. The article focuses particularly on
      approaches based on, and influenced by, psychology, sociology and social work
      when conducting narrative research. 

PMID- 24087878
TI  - OpenMSI: a high-performance web-based platform for mass spectrometry imaging.
AB  - Mass spectrometry imaging (MSI) enables researchers to directly probe endogenous
      molecules directly within the architecture of the biological matrix.
      Unfortunately, efficient access, management, and analysis of the data generated
      by MSI approaches remain major challenges to this rapidly developing field.
      Despite the availability of numerous dedicated file formats and software
      packages, it is a widely held viewpoint that the biggest challenge is simply
      opening, sharing, and analyzing a file without loss of information. Here we
      present OpenMSI, a software framework and platform that addresses these
      challenges via an advanced, high-performance, extensible file format and Web API
      for remote data access (http://openmsi.nersc.gov). The OpenMSI file format
      supports storage of raw MSI data, metadata, and derived analyses in a single,
      self-describing format based on HDF5 and is supported by a large range of
      analysis software (e.g., Matlab and R) and programming languages (e.g., C++,
      Fortran, and Python). Careful optimization of the storage layout of MSI data sets
      using chunking, compression, and data replication accelerates common, selective
      data access operations while minimizing data storage requirements and are
      critical enablers of rapid data I/O. The OpenMSI file format has shown to provide
      >2000-fold improvement for image access operations, enabling spectrum and image
      retrieval in less than 0.3 s across the Internet even for 50 GB MSI data sets. To
      make remote high-performance compute resources accessible for analysis and to
      facilitate data sharing and collaboration, we describe an easy-to-use yet
      powerful Web API, enabling fast and convenient access to MSI data, metadata, and
      derived analysis results stored remotely to facilitate high-performance data
      analysis and enable implementation of Web based data sharing, visualization, and
      analysis.

PMID- 24087879
TI  - Full color modulation of firefly luciferase through engineering with unified
      Stark effect.
AB  - The firefly luciferase has been a unique marking tool used in various bioimaging
      techniques. Extensive color modulation is strongly required to meet special
      marking demands; however, intentional and accurate wavelength tuning has yet to
      be achieved. Here, we demonstrate that the color shift of the firefly chromophore
      (OxyLH2-1) by internal and external fields can be described as a unified Stark
      shift. Electrostatic microenvironmental effects on fluorescent spectroscopy are
      modeled in vacuo through effective electric fields by using time-dependent
      density functional theory. A complete visible fluorescence spectrum of firefly
      chromophore is depicted, which enables one to control the emission in a specific
      color. As an application, the widely observed pH-correlated color shift is proved
      to be associated with the local Stark field generated by the trace water-ions
      (vicinal hydronium and hydroxide ions) at active sites close to the OxyLH2-1. 

PMID- 24087880
TI  - Pediatric Burkitt's lymphoma and diffuse B-cell lymphoma: are surveillance scans
      required?
AB  - Outcomes in pediatric B-Non-Hodgkin Lymphoma (B NHL) have improved with intensive
      chemotherapy protocols, with long-term survival now over 80%. However, long-term
      adverse effects of therapy and poor outcomes for patients who relapse remain
      challenges. In this study, we aimed to evaluate the potential risks and benefits
      of routine relapse surveillance imaging after the completion of therapy. We
      reviewed 44 B NHL patients diagnosed and treated at Texas Children's Cancer
      Center in the period between 2000 to 2011. All cross-sectional diagnostic imaging
      examinations performed for disease assessment after completion of chemotherapy
      were reviewed and cumulative radiation dosage from these examinations and the
      frequency of relapse detection by these examinations were recorded. Only 3
      patients of the 44 relapsed (6.8%), though none of the relapses were initially
      diagnosed by computed tomography (CT) or fludeoxyglucose positron emission
      tomography (FDG-PET) scans. Median effective dose of ionizing radiation per
      patient was 40.3 mSv with an average of 49.1 mSv (range 0-276 mSv). This single
      institution study highlights the low relapse rate in pediatric B-NHL with
      complete response at the end of therapy, the low sensitivity of early detection
      of relapse with surveillance CT or FDG-PET imaging, and the costs and potential
      increased risk of secondary malignancies from cumulative radiation exposure from
      surveillance imaging. We propose that routine surveillance CT or FDG-PET scans
      for these patients may not be necessary. 

PMID- 24087881
TI  - Complications and consent following decompressive craniectomy: an illustrative
      case study.
AB  - PRIMARY OBJECTIVE: To assess clinical outcome following restoration of cranial
      contour in a young male who had suffered a severe traumatic brain injury.
      RESEARCH DESIGN: Case report. METHODS AND PROCEDURES: A young male was assessed
      before and after cranial reconstructive surgery with a custom-made titanium
      plate. The patient had previously required a bifrontal decompressive craniectomy
      in order to control intractable intracranial hypertension due to neurotrauma.
      Following an autologous cranioplasty he made very little neurological recovery
      and remained wheelchair-bound with severe contractures and was only able to
      follow single stage commands. Over the following 2 years he developed extensive
      resorption of his bone flap such that it required augmentation. MAIN OUTCOMES AND
      RESULTS: After surgery he clinically improved such that he was able to
      communicate more effectively and, although he remained severely disabled and
      fully dependent, he was able to communicate that he would have provided consent
      for the initial decompressive procedure even if he had known that the eventual
      outcome would be survival with severe disability and total dependence.
      CONCLUSIONS: Long-term follow-up is required for patients with severe traumatic
      brain injury not only to assess outcome and complications, but also to assess how
      acceptable that outcome is for the patient and their families.

PMID- 24087882
TI  - Pharmacological profile, efficacy and safety of lixisenatide in type 2 diabetes
      mellitus.
AB  - INTRODUCTION: The global prevalence of type 2 diabetes mellitus (T2DM) is rapidly
      increasing and is associated with a high risk of microvascular and macrovascular
      complications. Although some glucose-lowering therapies are associated with
      hypoglycemia and weight gain, glucagon-like peptide-1 (GLP-1) receptor agonists
      represent a significant advance in the treatment of T2DM, as they provide
      effective glycemic control with a low incidence of hypoglycemia and a beneficial
      effect on body weight, as well as potential improvements in cardiovascular
      outcomes. AREAS COVERED: This article evaluates the pharmacological and clinical
      profile of the once-daily prandial GLP-1 receptor agonist lixisenatide for the
      treatment of T2DM. EXPERT OPINION: Once-daily prandial lixisenatide has been
      evaluated in an extensive clinical trials program, in which it was shown to have
      a favorable safety and tolerability profile, and to effectively improve metabolic
      control. The unique pharmacological properties of lixisenatide clearly
      differentiate it from other GLP-1 receptor agonists. As a once-daily agonist with
      a high affinity for the GLP-1 receptor, lixisenatide improves overall glycemic
      control, with particularly strong effects on postprandial plasma glucose levels.
      These attributes encourage the application of lixisenatide in those patients with
      extensive postprandial glucose excursions, or in combination with other
      antidiabetic drugs that have prevailing effects on fasting glucose levels.

PMID- 24087883
TI  - Highly chemoselective Rauhut-Currier reaction between maleimides and enones and
      dual phosphine-mediated one-pot synthesis of bicyclic and polycyclic skeletons.
AB  - A highly chemoselective phosphine-catalyzed Rauhut-Currier reaction between
      maleimides and enones has been realized under very mild conditions, affording the
      corresponding cross-coupling products in moderate to excellent yields. On the
      basis of this reaction, an efficient dual phosphine-mediated one-pot synthesis of
      bicyclic and polycyclic compounds containing a cyclopenta[c]pyrrole skeleton has
      been accordingly developed, which features a tandem sequence of intermolecular
      Rauhut-Currier reaction and intramolecular Wittig reaction. 

PMID- 24087884
TI  - Proton transfer in wild-type GFP and S205V mutant is reduced by conformational
      changes of residues in the proton wire.
AB  - To study the dynamics and mechanisms of the proton wire of wild type green
      fluorescence protein (wt-GFP) and its S205V mutant, we applied molecular dynamics
      (MD) simulations and compared the results with the X-ray structures of both
      proteins and with the proton transfer kinetics of these proteins studied by the
      time-resolved emission technique. The MD simulations for the wt-GFP show that, in
      the proton wire, the Ser205 exists in two conformations with similar
      probabilities. One conformation supports the proton transfer, and the other does
      not. The fluctuation between the two conformers is relatively slow. This result
      may explain the time-resolved emission spectrum's long-time fluorescence tail of
      the wt-GFP chromophore's protonated form. The MD simulations of the S205V mutant
      show that the water molecule in the proton wire is replaced by other bulk water
      molecules along the simulations of 60 ns. Furthermore, as in the wt-GFP, the
      Thr203 also exists in two conformations in which only one conformation supports
      the proton transfer. These two findings give an insight into the relatively slow
      proton transfer rate in the S205V mutant in comparison to the wt-GFP. 

PMID- 24087888
TI  - Magnetic structures of LiMBO3 (M = Mn, Fe, Co) lithiated transition metal
      borates.
AB  - The magnetic ordering within LiMBO3 compounds (M = Mn, Fe, and Co) has been
      explored by magnetization measurements and neutron powder diffraction. For all M,
      an incommensurately ordered magnetic phase is established on cooling, followed by
      a change to a commensurate long-range antiferromagnetic state below TN2 = 12(1) K
      for LiMnBO3, TN2 = 25(1) K for LiFeBO3, and TN2 = 12(1) K for LiCoBO3. For
      LiMnBO3, the magnetic ordering at T = 2 K exhibits a propagation vector k = (1,
      0, 0) and consists of antiferromagnetic chains that are coupled
      antiferromagnetically to each other, the magnetic moments being oriented along
      the [001] direction. In contrast, the magnetic order at T = 2 K in LiFeBO3 and
      LiCoBO3 exhibits a propagation vector of k = (1/2, 1/2, 1/2) and consists of
      ferromagnetic chains that are antiferromagnetically coupled. The magnetic moments
      lie roughly along the [023] direction within the bc plane for LiFeBO3, and along
      the [301] direction within the ac plane for LiCoBO3. The moment orientations in
      both LiMnBO3 and LiFeBO3 suggest an Ising character arising from unquenched
      orbital momentum due to unusual trigonal bipyrimidal coordination environments.
      No evidence of Ising behavior is found in the case of LiCoBO3.

PMID- 24087889
TI  - The riddle of Ballantyne's syndrome in the aspect of hydrops fetalis.
AB  - Ballantyne's syndrome, the combination of maternal generalized edema and fetal
      ascites, is rare and alarming in gestation. Early diagnosis might be useful in
      providing proper management of the fetus and aiming at an improved clinical
      result. The syndrome is an indication that HF is there, it has already started
      expanding the fetal torso and endangering the child-bearer's life. Despite the
      detailed investigation, no apparent cause for the emergence of the hydrops was
      identified.

PMID- 24087890
TI  - Importance of metal hydration on the selectivity of Mg2+ versus Ca2+ in magnesium
      ion channels.
AB  - Magnesium ion channels and transporters regulate the cellular concentrations of
      Mg(2+), which must be tightly controlled as imbalances have been associated with
      diseases such as osteoporosis, diabetes, and high blood pressure in humans. The
      channels and transporters allow the "native" Mg(2+) to be transported against a
      high background concentration of its major competitor, Ca(2+). Their selectivity
      filters (the narrowest part of the open pore) control metal ion selectivity. As
      the structures of Mg(2+) channels in an open conformation with bound Mg(2+) have
      not yet been solved, the key determinants of Mg(2+)/Ca(2+) selectivity in Mg(2+)
      ion channels remain elusive. Here, using density functional theory combined with
      continuum dielectric methods, we evaluated how the competition between Mg(2+) and
      Ca(2+) in model selectivity filters depends on the degree of metal hydration,
      which correlates with the pore size/rigidity as well as the composition and
      solvent accessibility of the selectivity filter. The key determinant of the
      selectivity for Mg(2+) over Ca(2+) in the Mg(2+) channel selectivity filter is a
      pore that is sufficiently large to accommodate hexahydrated Mg ions. In such wide
      pores, the hexahydrated metal ions interact indirectly with the protein ligands,
      hence metal desolvation and ligand-ligand steric repulsion become less important
      than Mg(2+)-water-protein interactions. These wide pores are Mg(2+)-selective
      because compared to Ca(2+) or Na(+) and K(+) monocations, Mg(2+) better polarizes
      the bound water molecules resulting in stronger Mg(2+)-water-protein
      interactions. Although both tetrameric and pentameric filters with pores that can
      accommodate hexahydrated metal ions could select Mg(2+) over Ca(2+), a bilayered
      pentameric filter lined with a ring of amides and a ring of carboxylates seems to
      best discriminate the "native" Mg(2+) from its key rival, Ca(2+). Our results are
      consistent with available experimental data and help to elucidate the selectivity
      filters in the Mg(2+)-selective TRPM6 and CorA channels. 

PMID- 24087891
TI  - Dosimetry of N6-formyllysine adducts following [13C2H2]-formaldehyde exposures in
      rats.
AB  - With formaldehyde as the major source of endogenous N6-formyllysine protein
      adducts, we quantified endogenous and exogenous N6-formyllysine in the nasal
      epithelium of rats exposed by inhalation to 0.7, 2, 5.8, and 9.1 ppm [13C2H2]
      formaldehyde using liquid chromatography-coupled tandem mass spectrometry.
      Exogenous N6-formyllysine was detected in the nasal epithelium, with
      concentration-dependent formation in total as well as fractionated (cytoplasmic,
      membrane, nuclear) proteins, but was not detected in the lung, liver, or bone
      marrow. Endogenous adducts dominated at all exposure conditions, with a 6 h 9.1
      ppm formaldehyde exposure resulting in one-third of the total load of N6
      formyllysine being derived from exogenous sources. The results parallel previous
      studies of formaldehyde-induced DNA adducts.

PMID- 24087892
TI  - Identification of enriched PTM crosstalk motifs from large-scale experimental
      data sets.
AB  - Post-translational modifications (PTMs) play an important role in the regulation
      of protein function. Mass spectrometry based proteomics experiments nowadays
      identify tens of thousands of PTMs in a single experiment. A wealth of data has
      therefore become publically available. Evidently the biological function of each
      PTM is the key question to be addressed; however, such analyses focus primarily
      on single PTM events. This ignores the fact that PTMs may act in concert in the
      regulation of protein function, a process termed PTM crosstalk. Relatively little
      is known on the frequency and functional relevance of crosstalk between PTM
      sites. In a bioinformatics approach, we extracted PTMs occurring in proximity in
      the protein sequence from publically available databases. These PTMs and their
      flanking sequences were subjected to stringent motif searches, including a
      scoring for evolutionary conservation. Our unprejudiced approach was able to
      detect a respectable set of motifs, of which about half were described
      previously. Among these we could add many new proteins harboring these motifs. We
      extracted also several novel motifs, which through their widespread appearance
      and high conservation may pinpoint at previously nonannotated concerted PTM
      actions. By employing network analyses on these proteins, we propose putative
      functional roles for these novel motifs with two PTM sites in close proximity. 

PMID- 24087893
TI  - Clinical assessment of PTSD in children with mild to borderline intellectual
      disabilities: a pilot study.
AB  - OBJECTIVE: There are few studies regarding assessment and treatment of trauma
      related disorders in people with intellectual disabilities (ID). The aims of this
      study were to determine (1) the feasibility of an adapted version of a post
      traumatic stress disorder (PTSD)-clinical interview and (2) to what extent
      manifestation of PTSD in a sample of children with mild to borderline ID
      corresponds with four existing PTSD algorithms. METHOD: Fifteen children who
      visited a special need school were interviewed. RESULTS: In all children, the
      full interview could be completed. Potentially traumatic events (A1 criterion),
      and PTSD symptoms for children with mild to borderline ID were similar to those
      observed in children without ID. CONCLUSIONS: The manifestation of PTSD in
      children with mild to borderline ID corresponds with the manifestation of PTSD in
      children without ID. The data provide no reason to broaden PTSD criterion A1 for
      children with mild to borderline ID.

PMID- 24087894
TI  - The effect of HFE polymorphisms on cardiac iron overload in patients with beta
      thalassemia major.
AB  - OBJECTIVE: We aimed to investigate the effect of human hemochromatosis protein
      (HFE) polymorphisms on cardiac iron overload in patients with beta-thalassemia
      major. METHODS: Our study included 33 patients diagnosed with beta-thalassemia
      major who were treated with regular transfusions and chelation therapy. M-mode,
      tissue Doppler, and pulsed wave Doppler echocardiography were performed on all
      patients. T2* magnetic resonance imaging (MRI) scans were also performed. The HFE
      polymorphisms (H63D, C282Y, S65C, Q283P, E168Q, E168X, W169X, P160delC, Q127H,
      H63H, V59M, and V53M) were studied using polymerase chain reaction. RESULTS: The
      H63D polymorphism was detected in six patients with beta-thalassemia major. Five
      patients were heterozygous for the H63D polymorphism, while one was homozygous.
      There were no other polymorphisms. There was no relationship between the HFE
      polymorphisms and either the serum ferritin levels or the T2-weighted MRI values
      (P > .05). Moreover, conventional echo and tissue Doppler echo findings were not
      correlated with the HFE polymorphisms. Pulmonary vein atrial reversal flow
      velocity, which is a manifestation of diastolic dysfunction measured with pulse
      wave echo, was higher in the patients with HFE polymorphisms (P = .036).
      CONCLUSIONS: The HFE polymorphisms had no effect on cardiac iron overload.
      However, pulmonary vein atrial reversal flow velocity measurements can provide
      important information for detecting diastolic dysfunction during cardiac follow
      up of patients with HFE polymorphisms. Studies with more patients are needed to
      provide more information regarding this matter.

PMID- 24087895
TI  - Infection control: a paradigm shift.

PMID- 24087896
TI  - Role of toxicogenomics in the development of safe, efficacious and novel anti
      microbial therapies.
AB  - Over the last two decades, occurrence of bacterial resistance to commonly used
      antibiotics has necessitated the development of safer and more potent anti
      microbial drugs. However, the development of novel antibiotics is severely
      hampered by adverse side effects, such as drug-induced liver toxicity. Several
      antibacterial drugs are known to have the potential to cause severe liver damage.
      The major challenge in developing novel anti-microbial drugs is to predict, with
      certain amount of probability, the drug-induced toxicity during the pre-clinical
      stages, thus optimizing and reducing the time and cost of drug development.
      Toxicogenomics approach is generally used to harness the potential of genomic
      tools and to understand the physiological basis of drug-induced toxicity based on
      the in-depth analysis of Metagenomic data sets, i.e., transcriptional,
      translational or metabolomic profiles. Toxicogenomics, therefore, represents a
      new paradigm in the drug development process, and is anticipated to play an
      invaluable role in future to develop safe and efficacious medicines, by
      predicting the toxic potential of a new chemical entity (NCE) in early stages of
      drug discovery. This review examines the toxicogenomic approach in predicting the
      safety/toxicity of novel anti-microbial drugs, and analyses the promises,
      pitfalls and challenges of applying this powerful technology to the drug
      development process. 

PMID- 24087897
TI  - pi-Conjugated zwitterions as paradigm of donor-acceptor building blocks in
      organic-based materials.
AB  - The very peculiar characteristics of zwitterions, as well as a clearand
      unambiguous definition, have been overlooked in past literature. However, these
      compounds are particularly important in view of the impact they have had in the
      recent past and will likely continue to have in the future as components of
      performing functional organic and hybrid materials. In this Account, we primarily
      aim to define critically important organic concepts of zwitterions regarding both
      their design and nomenclature. We will particularly focus on a specific kind of
      zwitterions we define as pi-conjugated zwitterions. These types of zwitterions
      are systems pertaining to the class ofdonor-acceptor (push-pull) molecules. In
      the ground state, they are preferentially represented in terms of an electron
      donor moiety bearing a negative net charge, and electron acceptor one bearing a
      positive net charge connected by a conjugated bridge. As such, they are possibly
      the most effective example of push-pull structure, possessing relevant features
      for applications like nonlinear optics, photovoltaics, imaging, and high
      capacitance dielectrics. In addition, the interaction between these dipolar
      compounds and the environment is highly specific and can be exploited in the
      construction of well-organized nanostructures, both in solution and in the solid
      state. According to the Gold Book of IUPAC for nomenclature, the distinction
      between zwitterions and the charged molecule called a betaine is subtle. The
      betaine is a particular class of zwitterion possessing an onium atom not bearing
      a hydrogen. The two terms are often considered equivalent, thus generating
      confusion while retrieving literature. In this Account, we define and describe pi
      conjugated zwitterions systems that are dipolar in the ground state, admitting
      resonance limiting structures that are neutral and chargeless. For the purpose of
      this Account and to the benefit of researchers striving to retrieve materials
      related zwitterion literature data, we suggest to use the term pi-zwitterions
      instead of the commonly used plain term "zwitterions". We show that this
      definition enables the clear identification of a class of compounds having unique
      properties distinct from "dipolar conjugated compounds." We describe the most
      common donor and acceptor groups in pi-zwitterions. In particular, we focus our
      attention on the special case of the nitrile functionality, which tends to be
      contiguous to a negative charge. We also address special emphasis to benzenoid
      components that are substituted by heteroaromatic units in pi-zwitterions,
      because the HOMO-LUMO energetic consequences are specifically involved in these
      cases. We make reference to the paradigmatic case of pi-zwitterions second order
      nonlinear optical properties. Here, the value of the first hyperpolarizability
      beta versus the alternation in bond length turns out to be a measure of the
      balance of the chargeless and the dipolar contribution to the description of the
      zwitterion ground state. We also report literature data, collected both from our
      group and others, concerning pi-zwitterions containing heteroaromatic and/or
      nitrile groups, those based on the most performing acceptors so far described,
      and merocyanines. With particular reference to merocyanines, we show how pi
      zwitterions can play a fundamental role in the fast growing field of organic
      photovoltaics. Finally, we present pi-zwitterions made up of heteroaromatic
      groups that open new scenarios in heteroaromatic chemistry. 

PMID- 24087898
TI  - Predictors of depressed mood 12 months after injury. Contribution of self
      efficacy and social support.
AB  - PURPOSE: There is evidence that depressed mood and perception of pain are related
      in patients with chronic illness. However, how individual resources such as self
      efficacy and social support play a role in this association remains unclear. The
      aim of this study was to investigate the influence of both variables as either
      moderator or mediator. METHOD: In a longitudinal study, 274 injured workers (M =
      43.24 years) were investigated. Data were collected on sociodemographics,
      depressed mood, pain, social support, and self-efficacy at three months post
      injury, and depressed mood one year post-injury. RESULTS: Hierarchical multiple
      linear regression analyses revealed that pain (beta = 0.14; p < 0.01) and social
      support (beta = -0.18; p < 0.001) were significant predictors of depressed mood.
      Self-efficacy moderated the relationship of pain (beta = -0.12; p < 0.05) and
      depressed mood after one year. Lower self-efficacy in combination with pain had a
      stronger impact than higher self-efficacy and pain on depressed mood. Social
      support did not moderate the association. CONCLUSIONS: Self-efficacy for managing
      pain is important in the development of depressed mood. According to the results
      of this study, we suggest that the detection of low social support and low self
      efficacy might be important in long-term rehabilitation process. IMPLICATIONS FOR
      REHABILITATION: Risk for depressed mood one year after an accident is high: One
      in five workers report depressed mood. Protective factors for depressed mood in
      injured workers needs to be considered in the rehabilitation. Focusing on
      resources like social support and self-efficacy could be protective against
      depressed mood. The early detection of low social support and low self-efficacy
      might be important in long-term rehabilitation processes.

PMID- 24087899
TI  - Surface conductivity and the streaming potential near a rotating disk-shaped
      sample.
AB  - Surface conductivity can complicate the determination of a sample's zeta
      potential from electrokinetic measurements. Correction factors have been derived
      to mitigate the problem for common systems such as particles, plates, and porous
      plugs. These factors are functions of the Dukhin number Du given by Ks/Ka where
      Ks is the surface conductivity, K is the electrolyte conductivity, and a is a
      length scale appropriate for the sample geometry. Here, the correction factor for
      the rotating disk geometry, in terms comparable to equations for particles,
      capillaries, and porous plugs, is shown to be f(Du) is approximately equal to 1 +
      1.516Du + 0.135Du(2). The reciprocal of the f(Du) equation expresses the factor
      by which surface conductivity reduces the measured streaming potential for a
      given sample's true zeta potential. The theory shows that surface conductivity is
      negligible in the rotating disk geometry for essentially all ionic strengths
      because the disk radius is the natural length scale for Du. The correction for
      surface conductivity for a KCl solution with an ionic strength equivalent to the
      ionic strength of pure water would be only 1% for a disk 10 mm in diameter. The
      ohmic resistance to the return of surface current from the disk's periphery
      through the bulk liquid to the axis is always much smaller than the resistance to
      the return of surface current back through the diffuse charge cloud of the double
      layer. The rotating disk geometry is unusual in this regard.

PMID- 24087902
TI  - Prevalence of nonmusculoskeletal versus musculoskeletal cases in a chiropractic
      student clinic.
AB  - Objective : We sought to identify the percentage of nonmusculoskeletal and
      musculoskeletal conditions treated by interns in the National University of
      Health Sciences (NUHS) Student Clinic compared to chiropractic and allopathic
      health care professionals. Methods : The information gathered was taken from the
      charts of patients treated in the fall trimester, dated September 12, 2011
      through December 9, 2011. The data collected included ICD-9 codes for the
      conditions treated, the number of patient visits, age, and gender, and was
      evaluated using Microsoft Excel. Results : Over half of the 113 eligible patients
      were women with a mean patient age of 28 years, an average of three treated
      diagnoses, and a mean of seven treatments. Those treated only for musculoskeletal
      conditions totaled 52% of the patients; 48% of the patients were treated for
      nonmusculoskeletal conditions, or musculoskeletal plus nonmusculoskeletal
      conditions. Conclusion : The NUHS Student Clinic interns are treating a greater
      percentage of nonmusculoskeletal conditions and a lesser percentage of
      musculoskeletal conditions than practicing chiropractic physicians. The student
      interns also treat a lesser percentage of nonmusculoskeletal and a greater
      percentage of musculoskeletal conditions than allopathic practitioners. This
      comparison would suggest that NUHS is nearing its institutional goal of training
      its student interns as primary care practitioners. 

PMID- 24087900
TI  - A beta-peptide agonist of the GLP-1 receptor, a class B GPCR.
AB  - Previous work has shown that certain beta(3)-peptides can effectively mimic the
      side chain display of an alpha-helix and inhibit interactions between proteins,
      both in vitro and in cultured cells. Here we describe a beta(3)-peptide analog of
      GLP-1, CC-3(Act), that interacts with the GLP-1R extracellular domain (nGLP-1R)
      in vitro in a manner that competes with exendin-4 and induces GLP-1R-dependent
      cAMP signaling in cultured CHO-K1 cells expressing GLP-1R. 

PMID- 24087903
TI  - Using computer-assisted learning to engage diverse learning styles in
      understanding business management principles.
AB  - Objective : Changes in small business and insurance present challenges for newly
      graduated chiropractors. Technology that reaches identified, diverse learning
      styles may assist the chiropractic student in business classes to meet course
      outcomes better. Thus, the purpose of our study is to determine if the use of
      technology-based instructional aids enhance students' mastery of course learning
      outcomes. Methods : Using convenience sampling, 86 students completed a survey
      assessing course learning outcomes, learning style, and the helpfulness of
      lecture and computer-assisted learning related to content mastery. Quantitative
      analyses occurred. Results : Although respondents reported not finding the
      computer-assisted learning as helpful as the lecture, significant relationships
      were found between pre- and post-assisted learning measures of the learning
      outcomes 1 and 2 for the visual and kinesthetic groups. Surprisingly, however,
      all learning style groups exhibited significant pre- and post-assisted learning
      appraisal relationships with learning outcomes 3 and 4. Conclusion : While
      evidence exists within the current study of a relationship between students'
      learning of the course content corollary to the use of technologic instructional
      aids, the exact nature of the relationship remains unclear. 

PMID- 24087905
TI  - Letters to the editor.

PMID- 24087906
TI  - A new problem. Contamination of botanicals by phthalates. Rapid detection tests.
AB  - The purity of solvents used in medical, herbal and food products is an essential
      prerequisite. This communication is focused on the possible occurrence of
      phthalates contaminant derived from the utilisation of plastic containers for
      solvents instead of glass containers. The contamination must be detected also in
      the derived marketed extracts, like botanical food supplements. 

PMID- 24087907
TI  - Bayesian-based ensemble source apportionment of PM2.5.
AB  - A Bayesian source apportionment (SA) method is developed to provide source impact
      estimates and associated uncertainties. Bayesian-based ensemble averaging of
      multiple models provides new source profiles for use in a chemical mass balance
      (CMB) SA of fine particulate matter (PM2.5). The approach estimates source
      impacts and their uncertainties by using a short-term application of four
      individual SA methods: three receptor-based models and one chemical transport
      model. The method is used to estimate two seasonal distributions of source
      profiles that are used in SA for a long-term PM2.5 data set. For each day in a
      long-term PM2.5 data set, 10 source profiles are sampled from these distributions
      and used in a CMB application, resulting in 10 SA results for each day. This
      formulation results in a distribution of daily source impacts rather than a
      single value. The average and standard deviation of the distribution are used as
      the final estimate of source impact and a measure of uncertainty, respectively.
      The Bayesian-based source impacts for biomass burning correlate better with
      observed levoglucosan (R(2) = 0.66) and water-soluble potassium (R(2) = 0.63)
      than source impacts estimated using more traditional methods and more closely
      agrees with observed total mass. The Bayesian approach also captures the expected
      seasonal variation of biomass burning and secondary impacts and results in fewer
      days with sources having zero impact. Sensitivity analysis found that using non
      informative prior weighting performed better than using weighting based on method
      derived uncertainties. This approach can be applied to long-term data sets from
      speciation network sites of the United States Environmental Protection Agency
      (U.S. EPA). In addition to providing results that are more consistent with
      independent observations and known emission sources being present, the
      distributions of source impacts can be used in epidemiologic analyses to estimate
      uncertainties associated with the SA results. 

PMID- 24087908
TI  - Ellipsoidal Janus nanoparticles adsorbed at the water-oil interface: some
      evidence of emergent behavior.
AB  - The equilibrium behavior of ellipsoidal Janus nanoparticles at water-oil
      interfaces was investigated using dissipative particle dynamics simulations. It
      was found that the orientation of the nanoparticles with respect to the interface
      depends on nanoparticle aspect ratio, on the amount of polar vs nonpolar surface
      groups, and on the interactions between the nanoparticles surface groups and
      aqueous and nonaqueous solvents. The changes in nanoparticle orientation are not
      always monotonic, probably because of a competition between different driving
      forces. For nanoparticles of high aspect ratio, steric effects seem to cause an
      isotropic-to-nematic phase transition as the surface coverage increases. It was
      observed that at a sufficiently high surface coverage the nanoparticles are most
      effective at reducing the interfacial tension when they lay with their longer
      axis parallel to the interface. The simulation results presented could be useful
      for the design of Pickering emulsions. 

PMID- 24087909
TI  - Can computerized working memory training improve impaired working memory,
      cognition and psychological health?
AB  - OBJECTIVE: To study if computerized working memory (WM) training, in the sub
      acute phase after acquired brain injury, in patients with impaired WM, improves
      WM, cognition and psychological health. RESEARCH DESIGN: A randomized study (n =
      47) with an intervention group (IG) and a control group (CG), mean age 47.7
      years. The WAIS-III NI, Digit span, Arithmetic, Letter-Number Sequences (Working
      Memory sub-scale), Spatial span, the Barrow Neurological Institute Screen for
      Higher Cerebral Functions (BNIS) and the self-rating scales DEX and HADS were
      administered at baseline and at follow-ups at 6 and 18 weeks. Both groups
      underwent integrated rehabilitation. The IG also trained with the computerized WM
      training program, Cogmed QM, which was offered to the CG and followed up after
      the study completion. RESULTS: Both groups improved after their WM training in
      Working Memory, BNIS and in Digit span, particularly the reversed section. Both
      the BNIS and the Digit span differed significantly between the IG and CG due to
      the greater improvement in the IG after their WM training. Psychological health
      improved as both groups reported less depressive symptoms and the CG also less
      anxiety, after the training. CONCLUSION: Results indicated that computerized WM
      training can improve working memory, cognition and psychological health.

PMID- 24087910
TI  - Strategies in mass spectrometry for the assignment of Cys-Cys disulfide
      connectivities in proteins.
AB  - Elucidating disulfide linkage patterns is a crucial part of protein
      characterization, for which mass spectrometry (MS) is now an indispensable
      analytical tool. In many cases, MS-based disulfide connectivity assignment is
      straightforwardly achieved using one-step protein fragmentation in the unreduced
      form followed by mass measurement of bridged fragments. By contrast, venom
      proteins, which are receiving increasing interest as potential therapeutics, are
      a challenge for MS-based disulfide assignment due to their numerous closely
      spaced cysteines and knotted disulfide structure, requiring creative strategies
      to determine their connectivity. Today, these include the use of an array of
      reagents for enzymatic and/or chemical cleavage, partial reduction, differential
      cysteine labeling and tandem MS. This review aims to describe the toolkit of
      techniques available to MS users approaching both straightforward and complex
      disulfide bridge assignments, with a particular focus on strategies utilizing
      standard instrumentation found in a well-equipped analytical or proteomics
      laboratory. 

PMID- 24087911
TI  - Constructions and experiences of sexual health among young, heterosexual,
      unmarried Muslim women immigrants in Australia.
AB  - Minority ethnic immigrant women are frequently vulnerable to poor sexual health
      outcomes, due to poor use of sexual health services, lack of knowledge and social
      stigma associated with the discussion of sexuality. This paper explores the
      sexual health accounts provided by a group of young, unmarried heterosexual
      Muslim women immigrants residing and studying in Sydney, an under-researched
      group in the Australian context. Ten semi-structured interviews were conducted,
      focusing on sex before marriage, spouse selection and contraceptive use. Feminist
      discourse analysis identified 'purity versus corruption' as the primary
      construction of women's sexuality, where women positioned their sexual behaviour
      as that of purity and uninvolvement or corruption through unwedded participation.
      The subthemes 'maintaining ignorance and naivety', 'remaining virginal', 'sex
      segregation' and 'the fallen woman' capture women's personal sexuality-related
      experiences and values within the context of their religious and cultural
      communities. Additional research with this community is needed to examine the
      effects of negative social constructions of sex on young sexually active Muslim
      women, as well as further research on young women's sexual health within
      immigrant communities. 

PMID- 24087912
TI  - Development and validity of the early clinical assessment of balance for young
      children with cerebral palsy.
AB  - OBJECTIVES: Validity of the Early Clinical Assessment of Balance (ECAB), to
      monitor postural stability in children with cerebral palsy (CP), was evaluated.
      METHODS: 410 children with CP, 1.5 to 5 years old, participated. Physical
      therapists scored children on the Movement Assessment of Infants Automatic
      Reactions section and Pediatric Balance Scale. Through consensus, researchers
      selected items from both measures to create the ECAB. Content and construct
      validity were examined through item correlations, comparison of ECAB scores among
      motor ability, age and gender groups and correlations with the Gross Motor
      Function Measure 66 basal and ceiling (GMFM-66-B&C). RESULTS: Internal
      consistency was high (Cronbach's alpha = 0.92). ECAB differed significantly among
      motor ability, children <31 months old scored lower than older children, but
      there was no difference between boys and girls. ECAB and GMFM-66-B&C scores
      correlated strongly (r = 0.97). CONCLUSION: Validity of the ECAB was supported.
      Reliability and responsiveness need study.

PMID- 24087914
TI  - Exploring the attitudes of pediatric oncologists toward the use of laxatives for
      the prevention of constipation in patients undergoing active treatment: a
      Canadian perspective.
AB  - BACKGROUND: Constipation is a common problem in pediatric oncology patients and
      may lead to significant consequences. There is a paucity of the published
      literature on the prevention of constipation in this population. The primary
      purpose of this study was to explore the current practice of pediatric
      oncologists in preventing constipation in children receiving active chemotherapy
      treatment, specifically during periods of intensive vincristine therapy. METHODS:
      A Web-based survey of pediatric oncologists and pediatric oncology trainees in
      Canadian centers was conducted. RESULTS: A 48% response rate was achieved. The
      majority of physicians had a lower threshold for defining constipation in
      oncology patients compared with the published literature. More than 90% of the
      respondents estimated the prevalence of constipation in pediatric oncology
      patients to be 30% or higher. The majority of respondents prescribed constipation
      prophylaxis in the presence of one or more of the following factors: history of
      constipation prior to or during previous phases of therapy, vincristine combined
      with either narcotics or immobility, multiple vincristine doses per month, spinal
      cord compression and immobility, and isolated narcotic therapy. Polyethylene
      glycol 3350, lactulose, and ducosate were the most commonly recommended first
      line prophylactic therapies used. CONCLUSION: Constipation is a significant
      problem in patients during cancer treatment. Most oncologists suggest giving
      laxatives as prophylaxis in the presence of risk factors, as well as prompt
      treatment once any symptoms appear. Our results suggest a role for the
      introduction of guidelines in the prevention of constipation, especially for
      patients receiving frequent vincristine therapy.

PMID- 24087917
TI  - Reexamination of gas production in the Bray-Liebhafsky reaction: what happened to
      O2 pulses?
AB  - Results of high-precision measurements of gas production in the BL reaction are
      presented, and an efficient kinetic model for their analysis is proposed. Based
      on this model, the data have been examined pulse by pulse, and for the first
      time, the entire records of gas production could be successfully reduced to
      series of just a few key parameters. It has been confirmed that the kinetics of
      O2(g) production is of the first order with respect to its precursor. Overall,
      only two steps have been found necessary to fit the observed pulses in gas
      production. The first step produces the precursor of the recorded O2(g), and its
      rate has two components. One component provides the peaks, and its approximation
      in the form of Gaussian functions has been found as satisfactory. The other
      component provides the constant baseline of gas production between the pulses.
      Finally, the precursor gives rise to O2(g) in the second step, and the simple
      first-order kinetics suggests that the precursor is otherwise relatively
      unreactive, making O2(aq) a logical candidate. However, the rate constant of this
      process showed almost perfect linearity with the actual concentrations of H2O2,
      and it was affected only little by variations in the rate of stirring. It thus
      seems possible that this final step in gas production, responsible for the
      majority of O2 produced in pulses, might not be the interphase transport O2(aq) 
      > O2(g), as expected. Instead, it might be a truly chemical process, giving rise
      to O2(g) in a reaction of H2O2 with another precursor, which is not involved
      significantly in any other process, but it is not O2(aq). If this is true, the
      second-order rate constant of this process in the system with initial composition
      of 0.360 M KIO3, 0.345 M H2O2, and 0.055 M HClO4 at 60  degrees C would be 0.25
      0.30 M(-1).s(-1), depending on the rate of stirring. 

PMID- 24087918
TI  - Details of the ultrafast DNA photo-cross-linking reaction of 3
      cyanovinylcarbazole nucleoside: cis-trans isomeric effect and the application for
      SNP-based genotyping.
AB  - To clarify the cis-trans isomeric effect on the ultrafast DNA photo-cross-linking
      reaction of 3-cyanovinylcarbazole nucleoside ((CNV)K) in the DNA duplex, which
      gives a single photodimer on the reversed-phase HPLC chromatogram, the kinetics
      of the cis-trans photoisomerization of (CNV)K in double-stranded DNA was
      evaluated. Since the photoisomerization rate constant for cis to trans
      isomerization in double-stranded DNA was significantly larger than that for trans
      to cis isomerization, and the thermodynamic stability of the trans isomer was
      higher than that of the cis isomer, it was strongly suggested that the trans
      isomer of (CNV)K is a reactive species of the photo-cross-linking reaction. (1)H
      (1)H NOESY analysis of the photoadduct consisting of (CNV)K and T also supported
      the trans-mediated photo-cross-linking reaction of (CNV)K. By using this
      ultrafast photo-cross-linking reaction for the molecular beacon-based SNPs
      typing, four individual Japanese rice strains were clearly distinguishable with
      simple photoirradiation and fluorescence imaging using double-stranded target
      DNAs. 

PMID- 24087919
TI  - Impacts of shale gas wastewater disposal on water quality in western
      Pennsylvania.
AB  - The safe disposal of liquid wastes associated with oil and gas production in the
      United States is a major challenge given their large volumes and typically high
      levels of contaminants. In Pennsylvania, oil and gas wastewater is sometimes
      treated at brine treatment facilities and discharged to local streams. This study
      examined the water quality and isotopic compositions of discharged effluents,
      surface waters, and stream sediments associated with a treatment facility site in
      western Pennsylvania. The elevated levels of chloride and bromide, combined with
      the strontium, radium, oxygen, and hydrogen isotopic compositions of the
      effluents reflect the composition of Marcellus Shale produced waters. The
      discharge of the effluent from the treatment facility increased downstream
      concentrations of chloride and bromide above background levels. Barium and radium
      were substantially (>90%) reduced in the treated effluents compared to
      concentrations in Marcellus Shale produced waters. Nonetheless, (226)Ra levels in
      stream sediments (544-8759 Bq/kg) at the point of discharge were ~200 times
      greater than upstream and background sediments (22-44 Bq/kg) and above
      radioactive waste disposal threshold regulations, posing potential environmental
      risks of radium bioaccumulation in localized areas of shale gas wastewater
      disposal.

PMID- 24087920
TI  - Indium(III)-catalyzed reductive bromination and iodination of carboxylic acids to
      alkyl bromides and iodides: scope, mechanism, and one-pot transformation to alkyl
      halides and amine derivatives.
AB  - Highly effective indium(III)-catalyzed reductive bromination or iodination of a
      variety of carboxylic acids with 1,1,3,3-tetramethyldisiloxane (TMDS) and a
      source of bromine or iodine is described. This functional group interconversion
      has high tolerance for several functional groups, such as halogens, a hydroxy
      group, a nitro group, an olefin part, and a sulfide moiety. This indium catalytic
      system is also applicable to the reductive iodination of aldehyded, acyl
      chlorides, and esters. Furthermore, this reducing system can be applied to the
      one-pot synthesis of alkyl halides and amine derivatives via the addition of
      nucleophiles. Insight into the reaction mechanism was gained via the time course
      of (1)H and (13)C NMR monitoring experiments and the corresponding stepwise
      reactions. 

PMID- 24087921
TI  - The specific characteristics of DIC syndrome vary with different clinical
      settings in the newborn.
AB  - Abstract Two hundred fourteen newborns with serious perinatal pathology
      (posthypoxic syndrome, sepsis, surgical intervention, etc.) were examined in
      progress, according to 27 parameters including coagulative, trombocitic, anti
      coagulative and fibrinolitic parts of hemostasis system. It was proved, that
      neonatal disseminated intravascular coagulation (DIC) syndrome had different
      hemostasiological patterns, which were connected with the genesis: sepsis,
      surgical intervention or posthypoxic syndrome. Precise periods of DIC syndrome
      are not always presented in newborns. DIC syndrome with neonatal sepsis has two
      different patterns (overcompensated and decompensated). The manifestation of
      trombo-hemorrhagic disorders and their characteristics depend on the genesis of
      DIC syndrome (e.g. an infection process and hyperbilirubinemia can provide the
      appearance of hemorrhagic syndrome). 

PMID- 24087922
TI  - Gene-environment interactions and the risk of childhood acute lymphoblastic
      leukemia: exploring the role of maternal folate genes and folic Acid
      fortification.
AB  - Few studies have evaluated the interaction of folic acid fortification and folate
      metabolic genes on the risk of childhood acute lymphoblastic leukemia (ALL).
      Because folate status is influenced by both intake and genetic variation, the
      objective of this study was to explore maternal folate metabolic gene-folic acid
      fortification interactions and the risk of childhood ALL. The study population
      consisted of 120 ALL case-parent triads recruited from Texas Children's Cancer
      Center between 2003 and 2010. For this analysis, we focused on 13 maternal single
      nucleotide polymorphisms (SNPs) in 5-methyltetrahydrofolate-homocysteine
      methyltransferase (MTR). Prefortification was defined as delivery before January
      1997 and postfortification as delivery in or after January 1997. We used a two
      step approach to evaluate gene-environment interactions. First, a case-only
      approach was used, as this design provides greater power in the assessment of
      gene-environment interactions compared to other approaches. Second, we confirmed
      all statistically significant interactions using a log-linear approach among case
      parent triads. Only one of 13 interactions evaluated was confirmed in step 2.
      Specifically, mothers with the minor allele of MTR rs1804742 and who delivered
      during the prefortification period were at a greater risk of having a child with
      ALL (OR = 1.54, 95% CI: 0.82-2.88), compared to those mothers who delivered
      during the postfortification period (OR = 0.81, 95% CI: 0.22-2.99, P for
      interaction = .03). In one of the few studies to evaluate maternal folate
      metabolic genotype-folic acid interactions, we found limited evidence that the
      maternal MTR rs1804742 appeared to interact with higher folic acid levels to
      influence childhood ALL risk. 

PMID- 24087923
TI  - The ICF-CY-based structural equation model of factors associated with
      participation in children with autism.
AB  - OBJECTIVE: The aim of this study was to apply the International Classification of
      Functioning, Disability and Health - Child and Youth (ICF-CY) framework to
      identify the factors related to the participation of children with autism.
      METHOD: A convenience sample included 162 preschool children with autism ages 36
      to 72 months. The raters collected data using the ICF-CY-based questionnaire as
      an instrument to construct the structural equation modeling of factors associated
      with participation. RESULTS: The internal structure of the model was acceptable,
      indicating that the observed variables would suffice in accounting for latent
      variables. The structural model showed that the performance of participation in
      children with autism was influenced by body functions and personal factors. All
      the variables accounted for 77% of the explained variance for activities and for
      participation by 71% of the children with autism. CONCLUSION: These findings may
      provide critical information pertaining to predictive factors of participation
      for parents, educators, and professionals who work with children with autism.

PMID- 24087924
TI  - Chlorinated coumarins from the polypore mushroom Fomitopsis officinalis and their
      activity against Mycobacterium tuberculosis.
AB  - An EtOH extract of the polypore mushroom Fomitopsis officinalis afforded two new
      naturally occurring chlorinated coumarins, which were identified as the
      previously synthesized compounds 6-chloro-4-phenyl-2H-chromen-2-one (1) and ethyl
      6-chloro-2-oxo-4-phenyl-2H-chromen-3-carboxylate (2). The structures of the two
      isolates were deduced by ab initio spectroscopic methods and confirmed by
      chemical synthesis. In addition, an analogue of each was synthesized as 7-chloro
      4-phenyl-2H-chromen-2-one (3) and ethyl 7-chloro-2-oxo-4-phenyl-2H-chromen-3
      carboxylate (4). All four compounds were characterized physicochemically, and
      their antimicrobial activity profiles revealed a narrow spectrum of activity with
      lowest MICs against the Mycobacterium tuberculosis complex. 

PMID- 24087925
TI  - Functional characterization of the trypanosome translational repressor SCD6.
AB  - The storage of translationally inactive mRNAs in cytosolic granules enables cells
      to react flexibly to environmental changes. In eukaryotes, Scd6 (suppressor of
      clathrin deficiency 6)/Rap55 (RNA-associated protein 55), a member of the LSm14
      (like-Sm14) family, is an important factor in the formation and activity of P
      bodies, where mRNA decay factors accumulate, in stress granules that store mRNAs
      under adverse conditions and in granules that store developmentally regulated
      mRNAs. SCD6 from Trypanosoma brucei (TbSCD6) shares the same domain architecture
      as orthologous proteins in other organisms and is also present in cytosolic
      granules (equivalent to P-bodies). We show that TbSCD6 is a general repressor of
      translation and that its depletion by RNAi results in a global increase in
      protein synthesis. With few exceptions, the steady-state levels of proteins are
      unchanged. TbSCD6 is not required for the formation of starvation-induced
      granules in trypanosomes, and unlike Scd6 from yeast, Plasmodium and all
      multicellular organisms analysed to date, it does not form a complex with the
      helicase Dhh1 (DExD/H-box helicase 1). In common with Xenopus laevis RAP55,
      TbSCD6 co-purifies with two arginine methyltransferases; moreover, TbSCD6 itself
      is methylated on three arginine residues. Finally, a detailed analysis identified
      roles for the Lsm and N-rich domains in both protein localization and
      translational repression.

PMID- 24087926
TI  - Bimetallic platonic Janus nanocrystals.
AB  - We demonstrate the creation of Ag-based bimetallic platonic Janus nanostructures
      by confining galvanic replacement reaction at a nanoscale interface on highly
      symmetrical nanostructures such as Ag nanocubes and nanooctahedra using reactive
      microcontact printing (MUCP). The extent of galvanic replacement reaction can be
      controlled kinetically to derive Janus nanostructures with Au nanodots deposited
      on either one or multiple facets of Ag nanocubes. The selective deposition of Au
      dots on a single facet of Ag nanocubes breaks the cubic symmetry and brings about
      unique and anisotropic plasmonic responses. High-resolution cathodoluminescence
      hyperspectral imaging of single Janus nanocube demonstrates that surface plasmon
      resonances corresponding to Au and Ag can be excited at different spots on one
      Janus nanocube. In addition, we demonstrate the fabrication of alternating
      Janus/non-Janus segments on 2D Ag nanowires by using a line-patterned
      polydimethylsiloxane (PDMS) stamp for galvanic replacement. Aside from Au, Pt and
      Pd can also be selectively deposited onto Ag nanocubes. These Janus
      nanostructures may find important applications in the field of plasmon-enhanced
      catalysis. 

PMID- 24087927
TI  - Regioselective rapid synthesis of fully substituted 1,2,3-triazoles mediated by
      propargyl cations.
AB  - Regioselective rapid triazole syntheses at low temperature are described. Organic
      azides and propargyl cations generated by acids gave fully substituted 1H-1,2,3
      triazoles. Most reactions could be performed in 5 min at not only rt but also -90
      degrees C. Both terminal and internal alkynes were acceptable, and the
      sterically bulky substituents could afford the products smoothly. Various types
      of three-component coupling reactions were demonstrated, and the presence of
      allenylaminodiazonium intermediates was indicated. 

PMID- 24087928
TI  - Proteomics and polycystic ovary syndrome.
AB  - Polycystic ovary syndrome (PCOS) is a complex endocrine disorder of heterogeneous
      etiology. Proteomics techniques have been used for elucidating the
      physiopathology of PCOS, yet the proteins identified so far were rarely the same
      across tissues and studies. The present review discusses the current challenges
      in the application of proteomics to the study of PCOS. A well-defined research
      design and an appropriate selection of study populations, samples and proteomic
      platforms are essential in clinical proteomics. Furthermore, the findings derived
      from proteomic approaches should be validated by complementary techniques, and
      the reproducibility of the results has ideally to be confirmed by different
      studies. Only when meeting these requirements, the proteins identified by
      proteomic techniques should be considered as candidates for future studies aiming
      to define specific molecular phenotypes of PCOS and their possible role in the
      metabolic and hormonal abnormalities characteristic of this syndrome. 

PMID- 24087929
TI  - Adsorption and release of siRNA from porous silica.
AB  - Porous silica particles are potential transfection agents for nucleic acid-based
      therapies because of their large specific surface areas and pore volumes and the
      ease with which they can be chemically modified to maximize the loading of cargo
      and to effect targeting in vivo. Here, we present a systematic study of the
      effects of pore size and pore modification on the adsorption and release of
      short, interfering RNA (siRNA) from a mesoporous silica particle developed in our
      laboratory. Using adsorption isotherms and release experiments, we found that the
      short polyamine diethylenetriamine was the best chemical modification for
      achieving both the adsorption and release of large amounts of siRNA. The degree
      of functionalization with diethylenetriamine caused drastic changes in the
      loading capacity and binding strength of siRNA to silica with relatively large
      pores (8 nm and larger), but the degree of functionalization had a weaker effect
      in narrow pores (4 nm). Multilayer adsorption could occur in materials with large
      pores (15 nm). Release experiments showed that intermediate pore sizes and
      intermediate degrees of functionalization resulted in the best compromise between
      maximizing loading (from strong adsorption) and maximizing release. Capillary
      electrophoresis and quantitative, real-time PCR demonstrated that siRNA was
      released intact and that these particles functioned as a transfection agent of
      mammalian cells in vitro. 

PMID- 24087930
TI  - Cationic amino acid based lipids as effective nonviral gene delivery vectors for
      primary cultured neurons.
AB  - The delivery of specific genes into neurons offers a potent approach for
      treatment of diseases as well as for the study of neuronal cell biology. Here we
      investigated the capabilities of cationic amino acid based lipid assemblies to
      act as nonviral gene delivery vectors in primary cultured neurons. An arginine
      based lipid, Arg-C3-Glu2C14, and a lysine-based lipid, Lys-C3-Glu2C14, with two
      different types of counterion, chloride ion (Cl-) and trifluoroacetic acid (TFA
      ), were shown to successfully mediate transfection of primary cultured neurons
      with plasmid DNA encoding green fluorescent protein. Among four types of lipids,
      we optimized their conditions such as the lipid-to-DNA ratio and the amount of
      pDNA and conducted a cytotoxicity assay at the same time. Overall, Arg-C3-Glu2C14
      with TFA- induced a rate of transfection in primary cultured neurons higher than
      that of Lys-C3-Glu2C14 using an optimal weight ratio of lipid-to-plasmid DNA of
      1. Moreover, it was suggested that Arg-C3-Glu2C14 with TFA- showed the optimized
      value higher than that of Lipofectamine2000 in experimental conditions. Thus, Arg
      C3-Glu2C14 with TFA- is a promising candidate as a reliable transfection reagent
      for primary cultured neurons with a relatively low cytotoxicity.

PMID- 24087931
TI  - Secondary malignant neoplasms following radiotherapy for primary cancer in
      children and young adults.
AB  - A study was conducted to investigate secondary malignant neoplasm (SMN)
      occurrence following radiotherapy (RT) for cancer in children and young adults,
      to examine the spatial distribution of SMNs in relation to the irradiated field,
      and to evaluate a possible role of bystander effects in SMN distribution. Forty
      two SMNs were identified among 7257 subjects diagnosed with cancer while living
      in Yorkshire, UK. Thirty-two of these occurred in patients receiving RT.
      Distances between SMN locations and RT field edge were estimated along with dose
      at SMN site. Expected radiation-induced SMN frequency in remote tissues receiving
      less than 0.1 Gy was predicted using risk estimates based on atomic bombing data.
      After a median follow-up period of 7.58 years, patients treated with RT were at a
      nearly five-fold increased risk of developing a subsequent primary neoplasm than
      the general population in the 0-29 years age range. The most common type of
      secondary malignancy associated with RT was of the central nervous system (28%),
      followed by sarcoma (25%) and leukemia (19%). Considering only solid SMNs
      developing 5 years or more from treatment, the spatial distribution showed a
      strong pattern of proximity to the irradiated field, with 68% occurring in-field
      or within 8 cm of the field edge. The SMN frequency in distant tissues receiving
      doses of less than 0.1 Gy was low but compatible with local absorbed dose. 

PMID- 24087932
TI  - Theoretical study of reaction of ketene with water in the gas phase: formation of
      acetic acid?
AB  - Production of acetic acid via gas-phase hydration of ketene by water (uncatalyzed
      and in the presence of an additional water molecule) was theoretically
      characterized using high-level coupled-cluster methods, followed by a two
      dimensional master equation analysis to compute thermal reaction rate constants.
      The results show that the formation of acetic acid quite likely occurs in high
      temperature combustion of biomass, but that the rate of formation should be
      negligible under ambient atmospheric conditions. 

PMID- 24087933
TI  - Weakly stabilized primary borenium cations and their dicationic dimers.
AB  - Hydride abstraction from monocationic hydride bridged salts [H(H2B-L)2](+)
      [B(C6F5)4]- (L = Lewis base) generates an observable primary borenium cation for
      L = iPr2NEt, but with L = Me3N, Me2NPr, or several N-heterocyclic carbenes,
      highly reactive dicationic dimers are formed. 

PMID- 24087934
TI  - Factors predicting early deterioration in mild brain trauma: a prospective study.
AB  - PRIMARY OBJECTIVE: To evaluate risk factors for clinical deterioration in mild
      traumatic brain injury. RESEARCH DESIGN: Prospective cross-sectional. METHODS AND
      PROCEDURES: This study evaluated 203 patients with mild traumatic brain injury. A
      brain computed tomography scan was performed in all patients and they were
      observed for 6-48 hours. MAIN OUTCOMES AND RESULTS: Among these patients, 2.5%
      had cerebral contusions and the most common sites for contusions were frontal
      lobes; 94% of patients had no hematoma in the initial scan, while 3% had
      subgaleal haematoma, 1.5% had subdural haematoma, 1% showed subarachnoid
      haemorrhage, 0.5% intracerebral haemorrhage and 0.5% epidural haemorrhage. GCS
      was 15 in 96.6% and 13-14 in 3.4%. GCS deteriorated in three (1.5%). Presence of
      coagulopathy, anticoagulant drug use, GCS of 13-14 and increased age predicted
      further deterioration. Among CT findings, those with midline shift, cerebral
      contusion and diffuse cerebral oedema deteriorated more. Among different
      haematoma types, only SDH predicted a worse outcome. CONCLUSIONS: Although
      deterioration rarely occurs in patients with mild brain injury, those with
      coagulopathy, anticoagulant drug use, GCS of 13-14, increased age, midline shift,
      cerebral contusions, diffuse cerebral oedema and SDH were more prone to
      deterioration.

PMID- 24087935
TI  - Self-report and caregiver-report of sleep and psychopathology in children with
      high-functioning autism spectrum disorder: A pilot study.
AB  - OBJECTIVE: To examine relationships between psychological and sleep problems in
      children with high-functioning autism spectrum disorder (HFASD) and typically
      developing (TD) children using self-report and caregiver-report. METHOD:
      Seventeen HFASD (M = 10.03 years, SD = 1.33) and 15 TD (M = 9.99 years, SD =
      1.22) children and their caregivers responded about the child's sleep, anxiety,
      depression and ADHD. RESULTS: Children with HFASD had poorer sleep than TD
      children by self-report and caregiver-report; caregiver-reported psychopathology,
      and self-reported anxiety were also higher for HFASD children. Poor sleep was
      related to anxiety in both groups, particularly Somatic-panic for HFASD children.
      Caregiver-child agreement for sleep and anxiety was fair for HFASD children but
      slight for TD children. CONCLUSIONS: Patterns of sleep-psychopathology
      associations differed for HFASD and TD children and hyperarousal seemed important
      for poor sleep in HFASD but not TD children. Results suggested that children with
      HFASD were able to report on their difficulties.

PMID- 24087936
TI  - How does catalase release nitric oxide? A computational structure-activity
      relationship study.
AB  - Hydroxyurea (HU) is the only FDA approved medication for treating sickle cell
      disease in adults. The primary mechanism of action is pharmacological elevation
      of nitric oxide (NO) levels which induces propagation of fetal hemoglobin. HU is
      known to undergo redox reactions with heme based enzymes like hemoglobin and
      catalase to produce NO. However, specific details about the HU based NO release
      remain unknown. Experimental studies indicate that interaction of HU with human
      catalase compound I produces NO. Presently, we combine flexible receptor-flexible
      substrate induced fit docking (IFD) with energy decomposition analyses to examine
      the atomic level details of a possible key step in the clinical conversion of HU
      to NO. Substrate binding modes of nine HU analogs with catalase compound I were
      investigated to determine the essential properties necessary for effective NO
      release. Three major binding orientations were found that provide insight into
      the possible reaction mechanisms for producing NO. Further results show that
      anion/radical intermediates produced as part of these mechanisms would be
      stabilized by hydrogen bonding interactions from distal residues His75, Asn148,
      Gln168, and oxoferryl-heme. These details will ideally contribute to both a
      clearer mechanistic picture and provide insights for future structure based drug
      design efforts. 

PMID- 24087937
TI  - Fatty acids, coumarins and polyphenolic compounds of Ficus carica L. cv. Dottato:
      variation of bioactive compounds and biological activity of aerial parts.
AB  - Leaves, bark and woody part of Ficus carica L. cultivar Dottato collected in
      different months were examined to assess their chemical composition, antioxidant
      activity and phototoxicity on C32 human melanoma cells after UVA irradiation. The
      phytochemical investigation revealed different composition in the coumarin, fatty
      acid, polyphenol and flavonoid content. The second harvest of leaves and the
      first harvest of the bark possessed the highest antiradical activity with IC50
      values of 64.00 +/- 0.59 and 67.00 +/- 1.09 MUg/mL, respectively. Harvest III of
      leaves showed the best inhibition of lipid peroxidation (IC50 = 1.48 +/- 0.04
      MUg/mL). Leaf samples of F. carica showed also the best antiproliferative
      activity in comparison with bark and woody part of F. carica. 

PMID- 24087938
TI  - Three-component cascade annulation of beta-ketothioamides promoted by CF3CH2OH: a
      regioselective synthesis of tetrasubstituted thiophenes.
AB  - A rapid and highly efficient method for the regioselective synthesis of thiophene
      derivatives has been developed by annulation of beta-ketothioamides with
      arylglyoxals and 5,5-dimethyl-1,3-cyclohexanedione in CF3CH2OH within 15 min. The
      present synthesis has several desirable features, such as high regioselectivity,
      a concise one-pot protocol, short reaction time, and easy purification. This
      methodology provides an alternative approach for easy access to tetrasubstituted
      thiophenes via a one-pot cascade reaction without other additives. 

PMID- 24087939
TI  - Spatiotemporal land use regression models of fine, ultrafine, and black carbon
      particulate matter in New Delhi, India.
AB  - Air pollution in New Delhi, India, is a significant environmental and health
      concern. To assess determinants of variability in air pollutant concentrations,
      we develop land use regression (LUR) models for fine particulate matter (PM2.5),
      black carbon (BC), and ultrafine particle number concentrations (UFPN). We used
      136 h (39 sites), 112 h (26 sites), 147 h (39 sites) of PM2.5, BC, and UFPN data
      respectively, to develop separate morning (0800-1200) and afternoon (1200-1800)
      models. Continuous measurements of PM2.5 and BC were also made at a single fixed
      rooftop site located in a high-income residential neighborhood. No continuous
      measurements of UFPN were available. In addition to spatial variables,
      measurements from the fixed continuous monitoring site were used as independent
      variables in the PM2.5 and BC models. The median concentrations (and
      interquartile range) of PM2.5, BC, and UFPN at LUR sites were 133 (96-232) MUg m(
      3), 11 (6-21) MUg m(-3), and 40 (27-72) * 10(3) cm(-3) respectively. In addition
      (a) for PM2.5 and BC, the temporal variability was higher than the spatial
      variability; (b) the magnitude and spatial variability in pollutant
      concentrations was higher during morning than during afternoon hours. Further,
      model R(2) values were higher for morning (for PM2.5, BC, and UFPN, respectively:
      0.85, 0.86, and 0.28) than for afternoon models (0.73, 0.69, and 0.23); (c) the
      PM2.5 and BC concentrations measured at LUR sites all over the city were strongly
      correlated with measured concentrations at a fixed rooftop site; (d) spatial
      patterns were similar for PM2.5 and BC but different for UFPN; (e) population
      density and road variables were statistically significant predictors of pollutant
      concentrations; and (f) available geographic predictors explained a much lower
      proportion of variability in measured PM2.5, BC, and UFPN than observed in other
      LUR studies, indicating the importance of temporal variability and suggesting the
      existence of uncharacterized sources. 

PMID- 24087940
TI  - Responsiveness to parenteral iron therapy in children with oral iron-refractory
      iron-deficiency anemia.
AB  - Intravenous (IV) ferric iron (Fe)-carbohydrate complexes are used for treating Fe
      deficiency in children with iron-refractory iron-deficiency anemia (IRIDA). An
      optimal treatment has yet to be determined. There are relatively little
      publications on the responsiveness to IV iron therapy in children with IRIDA.
      PATIENTS AND METHOD: This study analyzed responses to IV iron sucrose therapy
      given to 11 children, ranging in age from 2 to 13 years (mean 4.8 years), with
      iron-deficiency anemia who were unresponsive to oral iron therapy. RESULTS: The
      hemoglobin and ferritin values (mean) of the 11 children with IRIDA were 7.7 g/dL
      and 4.8 ng/mL at diagnosis. Both hemoglobin and ferritin levels increased to 9.5
      g/dL, and 24 ng/mL, respectively, at 6 weeks after the first therapy. Although
      the level of hemoglobin was steady at 6 months after the first, and 6 weeks after
      the second therapy, the ferritin levels continued to increase up to 30 ng/mL and
      47 ng/mL at 6 months after the first and 6 weeks after the second therapy,
      respectively. CONCLUSION: We recommend that IRIDA should be considered in
      patients presenting with iron-deficiency anemia of unknown cause that is
      unresponsive to oral iron therapy. Our results suggest that IV iron therapy
      should be administered only once in cases of IRIDA. Continued administration of
      IV iron would be of no benefit to increase hemoglobin levels. On the contrary,
      ferritin levels may continue to increase resulting in untoward effects of
      hyperferritinemia.

PMID- 24087941
TI  - Stopped-flow kinetic studies of poly(amidoamine) dendrimer-calf thymus DNA to
      form dendriplexes.
AB  - Poly(amidoamine) (PAMAM) dendrimers are known to be highly efficient nonviral
      carriers in gene delivery. Dendrimer-mediated transfection is known to be a
      function of the dendrimer to DNA charge ratio as well as the size of the
      dendrimer. In the present study, the binding kinetics of four PAMAM dendrimers
      (G1, G2, G3, and G4) with calf thymus DNA (CT-DNA) has been studied using stopped
      flow fluorescence spectroscopy. The effect of dendrimer-to-DNA charge ratio and
      dendrimer generation on the binding kinetics was investigated. In most cases, the
      results of dendrimer-CT-DNA binding can be explained by a two-step reaction
      mechanism: a rapid electrostatic binding between the dendrimer and DNA, followed
      by a conformational change of the dendrimer-DNA complex that ultimately leads to
      DNA condensation. It was observed that the charge ratio on the dendrimer and the
      DNA phosphate groups, as well as the dendrimer generation (size), has a marked
      effect on the kinetics of binding between the DNA and the dendrimers. The rate
      constant (k'1) of the first step was much higher compared to that of the second
      step (k'2), and both were found to increase with an increase in dendrimer
      concentration. Among the four generations of dendrimers, G4 exhibited
      significantly faster binding kinetics compared to the three smaller generation
      dendrimers.

PMID- 24087942
TI  - The reality of hospitalisation: Stories from family members of their hospital
      experience for adolescents and young adults living with and dying from cancer.
AB  - Abstract Background: Adolescents and Young Adults (AYA) with cancer are being
      disadvantaged within the present health care system. Some of the factors
      identified as leading to this disadvantage include medical issues specific to
      AYAs with cancer, delay in diagnosis, fragmented services, lack of access to
      clinical trials and psychosocial life stage issues Objective: A major study
      investigated the experience that accompanies the stages of diagnosis, treatment,
      dying and death of an AYA from the perspective of family members. This paper
      discusses the major theme of the reality of hospitalisation Methods: Narrative
      inquiry was the methodology for this study. The participants were a self-selected
      purposeful sample of 26 family members. Open-ended interviews were conducted to
      obtain a story of the experience of having an AYA family member live with and die
      of cancer. A meta-narrative of the family member's experience was developed by
      NVivo8. Results: In amongst the mass of data this study produced, a major theme
      to emerge was the experience 'of the reality of hospitalisation.' Within this
      theme issues regarding: the place of treatment; the hospital experience; not
      fitting in; and, confronting illness and death were revealed. Conclusion: While
      on the whole the cancer was treated with state of the art medicine, the
      experiences of the hospitalisation repeated consistently throughout this
      narrative reveals a failure to meet the higher order needs specific to
      adolelscents and young adults and their families As a result this cohort were
      exposed to a landscape which did not facilitate a therapeutic experience, as well
      as would be expected for children and older adults.

PMID- 24087945
TI  - Supporting parents and parenting: An overview of data-based papers recently
      published in Contemporary Nurse.
AB  - Abstract Nurses have a crucial role in play in supporting parents and in
      delivering and referring parents to family-support services. In this editorial,
      we reflect on papers recently published in Contemporary Nurse. We sought to
      consider data-based papers on parenting published between 2008 and 2012 and
      elucidate the role/s and potential roles of nurses in enhancing and supporting
      parenting. Parenting is recognised as a crucial variable for achieving positive
      outcomes for children (Dawson et al 2012). Poor, inconsistent or abusive
      parenting is linked to poor outcomes (Griffin et al. 2000, Holt et al.2008,
      Patterson et al.1989), while consistent and effective parenting is associated
      with enhanced child outcomes (Lamb 2012, Landry et al.2001). In addition to being
      important to outcomes for children, perceived parenting quality is also important
      to parents themselves. Disrupted relationships between parents and their children
      have been identified as distressing and potentially damaging to both parties
      (Jackson 2000; East 2006, 2007; Power 2012).

PMID- 24087947
TI  - Effect of Clinical Teaching Associate Model on Nursing Students' Clinical Skills
      and Nurses' Satisfaction.
AB  - Abstract Background and Objectives: The credit of the practice nurses in
      developing countries, due to gap between theory and practice in nursing education
      and health care delivery has been questioned by nursing professionals. Therefore,
      the aims of this study were to investigate the effectiveness of the application
      of the CTA model in nursing students' clinical skills and to assess the
      participants' (faculty members, staff nurses, and nursing students) level of
      satisfaction with the CTA model and with achieving the educational goals in Iran,
      as a developing country. Methods and Materials: In this experimental study,
      random sampling was used to assess 104 nursing students' clinical skills, and
      assess 6 faculty members and 6 staff nurses. After obtaining informed consent,
      the level of satisfaction was evaluated by a questionnaire and clinical skills
      were evaluated by standard checklists. Data were assessed and analyzed with SPSS
      version 15. Results: The results showed that the mean scores of all clinical
      skills of the students were significantly higher after intervention (p<0.01).
      Moreover, the mean scores of instructors' satisfaction with applying the CTA
      model was significantly higher (p = 0.004), but their satisfaction with achieving
      clinical education outcomes did not show a significant difference (p = 0.109).
      Similarly, students' satisfaction with achieving educational outcomes did not
      show any significant differences between the two groups (P = 0.058). Conclusion:
      According to this study, the CTA model is an effective method for developing
      clinical skills in nursing students in Iran as a developing country. Therefore,
      application of the method is recommended in clinical nursing education systems of
      such counties.

PMID- 24087949
TI  - Resolution of terminal 1,2-diols via silyl transfer.
AB  - Through kinetic analysis and optimization, we report an improved resolution of
      terminal 1,2-diols via asymmetric silyl transfer. Because the reaction is a
      regiodivergent resolution, the monoprotected product could be isolated in excess
      of 95:5 er and 40% yield. The described method offers a means of chemically
      differentiating a terminal 1,2-diol with concomitant resolution of the
      enantiomers. 

PMID- 24087950
TI  - Teratogenic effect of hydroxyethylrutoside, a flavonoid derivate drug--a
      population-based case-control study.
AB  - OBJECTIVE: Hydroxyethylrutoside (HER), a flavonoid derivate drug, used frequently
      in pregnant women for the treatment of vascular diseases. The aim of this case
      control study was to evaluate the teratogenic potential of oral HER treatment in
      the population-based Hungarian Case-Control Surveillance System of Congenital
      Abnormalities. METHODS: Comparative analysis of exposure (HER treatment) during
      pregnancy in the mothers of cases with congenital abnormalities and matched
      control newborns without any defect in the population-based Hungarian Case
      Control Surveillance System of Congenital Abnormalities. RESULTS: Of the 22,843
      cases with congenital abnormalities, 567 (2.5%) had mothers with HER treatment
      while of 38,151 matched controls, 1143 (3.0%) were born to mothers with HER
      treatment (OR with 95% CI: 0.8, 0.7-0.9). However, an association of HER
      treatment during the second and/or third month of pregnancy was found with the
      higher risk of unilateral ocular coloboma (OR with 95% CI: 5.4, 2.2-12.9) and a
      new congenital abnormality syndrome including anotia/microtia, poly/syndactyly
      and caudal (genital and anal) defects (OR with 95% CI: 3.0, 1.3-27.4).
      CONCLUSIONS: Oral HER treatment during early pregnancy associates with a higher
      risk for ocular coloboma and for a newly delineated congenital abnormality
      syndrome.

PMID- 24087953
TI  - [Genetic predictors of myocardial infarction in subjects of young age].
AB  - AIM OF THE STUDY: to investigate associations of single nucleotide polymorphisms
      (SNP) rs499818 (6p24.1), rs619203 of ROS1 gene (6q22), rs10757278 rs1333049
      (9p21.3), rs2549513 (16q23.1), rs4804611 of ZNF627 gene (19p13.2) with myocardial
      infarction in subjects of young age. The group of patients with MI (n=99) aged
      less than 45 years and the control group (n=111) did not differ significantly by
      sex (=0,617), age (=0.291), arterial hypertension (=0.766), diabetes mellitus
      (=0.395), hypercholestolemia (=0.696), excessive body mass and obesity (=0.361),
      abdominal obesity (=0.831) and history of smoking (=0.400). There was significant
      difference between groups by burdened heredity (<0.001). Genomic DNA was obtained
      from venous blood by phenol-chloroform extraction. Genetic testing was performed
      by real time polymerase chain reaction using 7900HT Fast Real-Time PCR System
      according to manufacturers protocol. We found significant association between
      rs1333049 and rs10757278 and myocardial infarction (MI). Odds ratio (OR) of
      development of MI in carriers of risk allele rs1333049 was 2.4 (95% confidence
      interval [CI] 1.24 to 4.65), in carriers of G rs10757278 allele - 2.00 (95%CI
      1.05 to 3.80). Association of risk alleles rs 1333049 and G rs10757278 with MI
      remained significant after adjustment for burdened family history (OR 4.25, 95%CI
      1.39 to 12.99, and OR 3.04, 95%CI 1.09 to 8.52, respectively). Presence in the
      genotype of both risk alleles rs1333049 and G rs10757278 was associated with OR
      of MI development 2.40 (95%CI 1.20 to 4.82) which was not different from that
      associated with carriage of allele rs1333049 only. Possibly in our population
      both SNPs belong to one linkage block and correspondingly it is sufficient to
      genotype one SNP. No significant associations with MI were found for variants
      rs4804611, rs2549513, rs499818, rs619203. SNPs rs1333049 and rs10757278 of 9p21.3
      locus are predictors of MI in young individuals not dependent on both traditional
      risk factors and presence of burdened family history.

PMID- 24087951
TI  - New generation of ensemble-decision aliquot ranking based on simplified
      microfluidic components for large-capacity trapping of circulating tumor cells.
AB  - Ensemble-decision aliquot ranking (eDAR) is a sensitive and high-throughput
      method to analyze circulating tumor cells (CTCs) from peripheral blood. Here, we
      report the next generation of eDAR, where we designed and optimized a new
      hydrodynamic switching scheme for the active sorting step in eDAR, which provided
      fast cell sorting with an improved reproducibility and stability. The
      microfluidic chip was also simplified by incorporating a functional area for
      subsequent purification using microslits fabricated by standard lithography
      method. Using the reported second generation of eDAR, we were able to analyze 1
      mL of whole-blood samples in 12.5 min, with a 95% recovery and a zero false
      positive rate (n = 15). 

PMID- 24087954
TI  - [Optimal timing of the second stage of revascularization in the treatment of
      patients with ST-elevation myocardial infarction and multivascular involvement].
AB  - An assessment of outcomes in 187 patients with ST elevation myocardial infarction
      (STEMI) with multivessel coronary disease who underwent primary percutaneous
      coronary intervention (PCI) was done. All patients were divided into two groups:
      in group 1 (n=39) second phase of revasculrization was performed within 60 days,
      in group 2 (n=148) it was carried out or planned in more than 60 days after index
      event. During 12 months of follow up rates of combined end point (death,
      myocardial infarction, target vessel revascularization [TVR]) and TVR in group 1
      were lower than in group 2 (5.1 vs 27.7%, and 0 vs 11.5%, respectivelly, p=0.05).
      We also observed tendency to lower reinfarction rate in group 1 (0 vs 9.46%,
      p=0.09). There was no significant difference between groups in number of deaths
      (5.1% vs 6.7%, respectively). 

PMID- 24087955
TI  - [Achievement of goal resting heart rate in patients with stable angina and
      hypertension at the background of therapy with -adrenoblockers in real clinical
      practice].
AB  - beta-Adrenoblockers improve quality of life and in a number of cases life
      prognosis in patients with stable angina (SA). Dose of -adrenoblockers is
      considered optimal if at the background of treatment resting heart rate (rHR) is
      persistently decreased down to 55-60 bpm. But according to data of international
      registries rate of achievement of target rHR (trHR) in real clinical practice
      does not exceed 22%. Aim of this study was to determine what portion of patients
      with SA and arterial hypertension (AH) achieves trHR at the background of therapy
      with -adrenoblockers in routine practice in this country. Twenty centers in 6
      towns in Russian Federation recruited 399 patients (mean age 64+/-10 years) with
      class I-III angina and concomitant primary AH. These patients for at least 2
      months received any -adrenoblocker and did not change its dose during 4 weeks
      before inclusion into the program. Portion of patients with trHR was 15.5%. There
      were no significant differences between average daily doses of most frequently
      used -adrenoblockers (metoprolol, bisoprolol, carvediolol) in groups of patients
      who achieved and did not achieve trHR. Quality of life of patients who achieved
      was comparable with that of those who did not achieve trHR. Attainment of trHR
      was associated with significant decrease of short acting requirement nitrates.
      There was a significant direct correlation between attainment of trHR and target
      arterial pressure.

PMID- 24087956
TI  - [Vasomotor endothelial dysfunction in young men with grade 1 arterial
      hypertension].
AB  - In order to study vasomotor endothelial function and risk factors of endothelial
      dysfunction in young men with grade 1 arterial hypertension (G1AH) we examined 76
      men with G1AH and 30 healthy men aged 20-40 years. Flow-mediated vasodilatation
      (FMD) of the brachial artery was assessed by ultrasonic method of Celermajer D.S.
      Vasomotor endothelial dysfunction (FMD<6%) was found significantly more
      frequently in men with G1AH than in healthy men (51% vs 13%). In healthy young
      men with normal blood pressure smoking was the main risk factor of endothelial
      dysfunction. In young men with G1AH risk factors for endothelial dysfunction
      were: family history of early cardiovascular disease, smoking, and elevation of
      low-density cholesterol level. Probability of endothelial dysfunction in the
      absence of these factors was low - 11%, in the presence of one factor it was 30%,
      two factors - 60%, and three factors - 83%. Elevated (>14.8%) red blood cell
      distribution width (RDW) was associated with endothelial dysfunction. Probability
      of endothelial dysfunction in young men with G1AH and elevated RDW was 5 times
      greater than in those with normal RDW. 

PMID- 24087957
TI  - [Regional results of the program FORTISSIMO in Kazan].

PMID- 24087958
TI  - [Prognostic value of left bundle brunch block in patients with acute coronary
      syndrome].
AB  - AIM: to assess rognostic value of ECG signs of left bundle brunch block (LBBB)
      using database of registries of acute coronary syndromes (ACS) RECORD 1 (2007
      2008) and 2 (2009-2011). MATERIAL AND METHODS: Total number of included patients
      was 2452, 2321 patients (94.9%) had no signs of LBBB, for 5 patients (0.2%) there
      was no information on the presence of LBBB. Among 126 patients (5.1%) with LBBB
      it was designated as "new" in 72 (2.9%), "old" in 39 (1.6%), and of "unknown
      duration" in 15 (0.6%) patients. For further analysis we combined patients with
      "new" and "unknown duration" LBBB (n=87 [3.5%]). Among these patients 43 (49.5%)
      were considered as having ST elevation (STE) and 44 (50/5%) - non STE ACS.
      RESULTS: Patients with LBBB were significantly older, had more concomitant
      diseases, more severe course of ACS, and higher GRACE score. Patients with new
      LBBB irrespective of ACS type significantly less often received active drug
      therapy while reperfusion therapy was significantly less often used in patients
      with LBBB and diagnosed STE myocardial infarction. Unfavorable events such as
      cardiogenic shock, death, death and myocardial infarction during hospitalization
      occurred more often among patients with STEACS and new LBBB. CONCLUSION: Patients
      with ECG signs of LBBB at the background of ACS were characterized by severe
      clinical course of the disease and have unfavorable short term prognosis. However
      quality of hospital care of these patients was significantly worse compared with
      average quality of care of patients with ACS without LBBB.

PMID- 24087959
TI  - [Chronic heart failure in patients with arterial hypertension and ischemic heart
      desease: age and gender characteristics].
AB  - AIM: to study prevalence of chronic heart failure (CHF) among patients with
      arterial hypertension (AH) and ischemic heart disease (IHD), and specific
      features of CHF in patients with different sex and age. MATERIAL AND METHODS: We
      carried out retrospective analysis of CHF prevalence in 2048 patients with AH
      and/or IHD and prospective study of distribution of clinical hemodynamic variants
      of CHF in 285 patients with known data of echocardiography and 6-min walk test.
      RESULTS AND CONCLUSION: The prevalence of CHF in our group was 29%, in men it was
      2.8 times greater than in women. Most patients with CHF (71%) were older than 60
      years. Significant differences were revealed in etiology of CHF between men and
      women, and between patients of different ages. CHF with EF<45% was diagnosed in
      35.8% of patients, Number of patients with EF<45% among men was 5.8 times greater
      than among women. CHF with preserved EF was found in 64.2% of patients.
      Purposeful examination of patients with AH and IHD is needed for early detection
      of CHF.

PMID- 24087960
TI  - [alpha-2beta-adrenoreceptor gene polymorphism in patients with disorders of
      cardiac conduction].
AB  - The article is devoted to the role of insertion-deletion polymorphism of -2
      adrenoreceptor gene in development of hereditary disorders of cardiac conduction.
      We examined 71 patients with atrioventricular blocks and 92 patients with sick
      sinus node syndrome. Statistically significant preponderance of homozygous
      genotype DD of ADRA2B gene was found in both groups. Associations of alleles with
      male or female gender were also revealed. 

PMID- 24087961
TI  - [Assessment of results of transesophageal echocardiography in patients with
      atrial flutter].
AB  - We performed 89 transesophageal electric cardiac stimulation procedures (TEECS)
      in order to restore sinus rhythm in 75 (84.3%) men and 14 (15.7%) women with type
      I atrial flutter (AF) due to coronary heart disease (n=59, 66.3%) and
      cardiosclerosis after myocarditis (n=30, 33.7%). Before cardioversion all
      patients underwent transthoracic and transesophageal echocardiography. All
      patients were divided into two groups: in group I (n=39) mean left atrium
      appendage ejection velocity was less or equal 40 cm/s, in group 2 (n=50) - > 40
      cm/s. Patients of group I had significantly longer duration of AF episode, more
      often had concomitant hypertension and atrial fibrillation. Cardioversion in
      group I was less effective with frequent relapses and transformation into
      constant form. Patients of group 2 had no spontaneous contrast phenomenon grade
      II-IV and intra-atrial hemodynamics of type II-III, while at TEECS cardioversion
      straight into sinus rhythm without episode of transient fibrillation was observed
      significantly more frequently, suggesting possibility of shortening of
      anticoagulant preparation period before the procedure. 

PMID- 24087962
TI  - [Arterial stiffness in patients with chronic obstructive lung disease in the
      presence and absence of ischemic heart disease].
AB  - Aim of the study was assessment of arterial stiffness in patients with chronic
      obstructive lung disease (COPD) with or without ischemic heart disease (IHD). We
      included in this open study 130 COPD patients older than 40 years (mean age
      60.2+/-8.3 years). Patients with clinical signs of exacerbation of other severe
      chronic diseases were not included. Control group comprised 18 practically
      healthy volunteers older than 50years (mean age 56.9+/-7.2 years). Tensioclinic
      arteriograph was used for evaluation of arterial wall stiffness. The study
      revealed increase of pulse wave propagation velocity associated with elevation of
      augmentation indexes in COPD patients both with and without IHD as well as in
      patients with different degrees of 10-year risk of cardiovascular death. These
      changes can be considered as systemic manifestations of COPD possibly underlining
      interrelationships between COPD and cardiovascular diseases. 

PMID- 24087963
TI  - [Analysis of approaches to assessment of persistent loss of capacity to work in
      patients who had undergone coronary bypass surgery].
AB  - Aim of the study was to assess factors influencing decisions about persistent
      disability of patients after coronary bypass surgery (CBS). By method of
      continuous sampling (registry study) we examined 427 working age patients who had
      undergone CBS. Although surgical treatment was effective rehabilitating factor
      most patients after CBS at inspection in institutions of medical social expertise
      were unreasonably classified as having low degree of restoration of ability to
      work. Possible explanations of this were incomplete volume of conducted tests,
      lack of relation between presence of functional class of angina and real clinical
      picture of this syndrome, absence of objective criteria of the presence of
      myocardial ischemia and tolerance to physical exercise, ill-timed referral to
      medical social inspection. 

PMID- 24087964
TI  - [Second Moscow International Forum of Cardiologists: main results].

PMID- 24087965
TI  - [The differences between the guidelines of the European Society of Cardiology and
      the American College of Cardiology/ American Heart Association for oral P2Y12
      inhibitor therapy in the management of patients with acute coronary syndromes].
AB  - The analysis of the evidence that formed the basis for the current guidelines of
      the European Society of Cardiology (ESC) on oral therapy by antithrombotic drugs
      for acute coronary syndromes (ACS), and a comparison with the U.S. guidelines.
      The ESC guidelines, published during 2011-2012, declared the superiority of
      prasugrel and ticagrelor over clopidogrel in patients with ACS without ST
      elevation and myocardial infarction (MI) with ST elevation. These guidelines are
      based in each case on a subgroup analysis of a single study using either
      prasugrel (TRITON), or ticagrelor (PLATO). In contrast, the American College of
      Cardiology (ACC) and the American Heart Association (AHA) guidelines, published
      in 2012-2013, are more balanced, conservative and present evidence-based outlook,
      suggesting no proven extra benefit of one P2Y12 antagonist over the other(s). The
      ESC guidelines regarding the findings of the superiority of prasugrel or
      ticagrelor over clopidogrel are overly optimistic and not always evidence-based.
      A small frequency of clinical use of prasugrel and ticagrelor in the world in
      general and Europe in particular, suggests a discrepancy between the
      traditionally appointed treatment and published ESC guidelines. 

PMID- 24087966
TI  - [The renin-angiotensin-aldosterone system and vascular aging].
AB  - In this paper we discuss the role of renin-angiotensin-aldosterone system in
      development of morphological and functional changes in the vascular aging as well
      as, possibility of its correction by using different groups of drugs. 

PMID- 24087967
TI  - [Comorbidity in cardiac pathology: clinical-organizational and epidemiological
      problems].
AB  - Scientific (analytical) approach directs researcher to the study of nosology in
      isolated native view. The phenomenon under consideration- comorbidity becomes
      significant and to a substantial degree is able to affect all aspects of the
      process of medical care. This is shown in this review along such directions as
      frequency of overt or concealed comorbidity or real state of the problem;
      magnitude of intracardiac and extracardiac comorbidity; difficulties of
      diagnostics and treatment arising with comorbidity; problems of validity of
      statistical (and epidemiological) side of the matter; value of social and
      organizational aspects of patients care in situations when comorbidity is
      present. 

PMID- 24087968
TI  - [Electrocardiographic sign of secondary atrial tumor presentation].
AB  - Two cases of intravital diagnosis of left atrial tumor secondary to lung cancer
      and esophagus cancer are presented. The myocardial alteration was caused by
      direct invasion of primary tumor. In both cases the PQ (PR) segment depression
      was found on ECG, which could reflect neoplastic lesion of the atrium. We
      proposed to consider this phenomenon as ECG marker of secondary atrial
      malignancies. 

PMID- 24087971
TI  - Thermal effects associated with the Raman spectroscopy of WO3 gas-sensor
      materials.
AB  - Metal oxides are suitable for detecting, through conductive measurements, a
      variety of reducing and oxidizing gases in environmental and sensing
      applications. Metal-oxide gas sensors can be developed with the goal of sensing
      gases under specific conditions and, as a whole, are heavily dependent on the
      manufacturing process. Tungsten oxide (WO3) is a promising metal-oxide material
      for gas-sensing applications. The purpose of this paper is to determine the
      existence of a correlation between thermal effects and the changes in the Raman
      spectra for multiple WO3 structures. We have obtained results utilizing Raman
      spectroscopy for three different structures of WO3 (monoclinic WO3 on Si
      substrate, nanopowder, and nanowires) that have been subjected to temperatures in
      the range of 30-160  degrees C. The major vibrational modes of the WO3:Si and the
      nanopowder samples, located at ~807, ~716, and ~271 cm(-1), correspond to the
      stretching of O-W-O bonds, the stretching of W-O, and the bending of O-W-O,
      respectively; these are consistent with a monoclinic WO3 structure. However in
      the nanowires sample only asymmetric stretching of the W-O bonds occurs,
      resulting in a 750 cm(-1) band, and the bending of the O-W-O mode (271 cm(-1)) is
      a stretching mode (239 cm(-1)) instead, suggesting the nanowires are not strictly
      monoclinic. The most notable effect of increasing the temperature of the samples
      is the appearance of the bending mode of W-OH bonds in the approximate range of
      1550-1150 cm(-1), which is related to O-H bonding caused by humidity effects. In
      addition, features such as those at 750 cm(-1) for nanowires and at 492 and 670
      cm(-1) for WO3:Si disappear as the temperature increases. A deeper understanding
      of the effect that temperature has on the Raman spectral characteristics of a
      metal oxide such as WO3 has helped to extend our knowledge regarding the behavior
      of metal oxide-gas interactions for sensing applications. This, in turn, will
      help to develop theoretical models for the identification of specific metal oxide
      gas relationships.

PMID- 24087969
TI  - Transannular Diels-Alder/1,3-dipolar cycloaddition cascade of 1,3,4-oxadiazoles:
      total synthesis of a unique set of vinblastine analogues.
AB  - A powerful tandem [4 + 2]/[3 + 2] cycloaddition cascade of 1,3,4-oxadiazoles
      initiated by a transannular [4 + 2] cycloaddition is detailed. An impressive four
      rings, four carbon-carbon bonds, and six stereocenters are set on each site of
      the newly formed central six-membered ring in a cascade thermal reaction that
      proceeds at temperatures as low as 80  degrees C. The resulting cycloadducts
      provide the basis for the synthesis of unique analogues of vinblastine containing
      metabolically benign deep-seated cyclic modifications at the C3/C4 centers of the
      vindoline-derived subunit of the natural product. 

PMID- 24087972
TI  - Rh(I) complexes bearing N,N and N,P ligands anchored on glassy carbon electrodes:
      toward recyclable hydroamination catalysts.
AB  - A series of N,N-donor ligands (bis(pyrazol-1-yl)methane (bpm), bis(N
      methylimidazol-2-yl)methane (bim), 1-(phenylmethyl)-4-(1H-pyrazol-1-yl methyl)-1H
      1,2,3-triazole (PyT)), and one N,P-donor ligand precursor (1-(3,5-dimethylpyrazol
      1-yl)(2-bromoethane) (dmPyBr)) were synthesized and functionalized with aniline.
      Diazotization of the aniline into an aryl diazonium, using nitrous acid in
      aqueous conditions, was performed in situ such that the ligands could be
      reductively adsorbed onto glassy carbon electrode surfaces. The N,N-donor ligands
      (bpm, bim, PyT) were immobilized in a single step, while several steps were
      required to immobilize the N,P-donor ligand (dmPyP) to prevent oxidation of the
      phosphine group. The complexation of the anchored ligands with the metal complex
      precursor ([Rh(CO)2(MU-Cl)]2) led to the formation of anchored Rh(I) complexes
      with each of the ligands (bpm, bim, PyT, dmPyP). X-ray photoelectron spectroscopy
      (XPS) confirmed the formation of the anchored ligands as well as the anchored
      complexes. The surface coverage of functionalized electrodes was estimated by
      means of cyclic voltammetry, and the nature of the coverage was close to being a
      monolayer for each immobilized complex. The anchored Rh(I) complexes were active
      as catalysts for the intramolecular hydroamination of 4-pentyn-1-amine to form 2
      methyl-1-pyrroline.

PMID- 24087974
TI  - Is participation among children with intellectual disabilities in outside school
      activities similar to their typically developing peers? A systematic review.
AB  - OBJECTIVE: To compare the extent, context and experience of participation in
      outside school activities of children with intellectual disability (ID) and their
      peers with typical development (TD). METHODS: A systematic review was completed.
      Nine databases were searched and citation tracking performed. Included studies
      were in English, published in a peer-reviewed journal, used a quantitative study
      design and compared children with ID to children with TD. Studies were assessed
      for quality using 15 items from the Downs and Black quality checklist. RESULTS:
      Four papers were included. Participants were reported to have similar
      participation in leisure activities. Children with ID were reported to
      participate in fewer community-based social activities, recreational, family
      enrichment and formal activities than children with TD. CONCLUSION: Key
      differences in participation between the groups were identified. Given their
      methodological limitations and that most studies were published prior to the
      International Classification of Functioning, Disability and Health, further
      research is required.

PMID- 24087975
TI  - The medication regimen review: building rapport with the consultant pharmacist.

PMID- 24087973
TI  - The clinical and cost-benefits of investing in neurobehavioural rehabilitation: a
      multi-centre study.
AB  - PRIMARY OBJECTIVE: The aim of this study was to investigate the cost-benefits of
      a residential post-acute neurobehavioural rehabilitation programme and its
      effects on care needs and social participation of adults with acquired brain
      injury. RESEARCH DESIGN: Retrospective multi-centre design. METHODS AND
      PROCEDURES: Data on occupation, adaptability and level of support required were
      collected at admission, discharge and 6-months follow-up. Cost analysis was
      performed on cost estimates based on level of support. MAIN OUTCOMES AND RESULTS:
      Significant gains were observed in all areas of functioning, with individuals
      progressing towards higher levels of independence and more participation in
      society upon discharge. CONCLUSIONS: Cost-benefits of up to L1.13 million were
      demonstrated for individuals admitted to rehabilitation within a year of
      sustaining a brain injury and of up to L0.86 million for those admitted more than
      1 year after injury. Functional gains and reductions in levels of care required
      upon discharge were maintained 6 months later. These results demonstrate that
      post-acute neurobehavioural rehabilitation can have a positive impact on the
      lives of individuals with brain injury and that the associated costs are off-set
      by significant savings in the longer-term.

PMID- 24087979
TI  - Covalent modification of photoanodes for stable dye-sensitized solar cells.
AB  - This paper describes the surface modification of TiO2 with 3
      aminopropyltriethoxysilane (APTES) followed by covalent attachment of Ru-based
      N719 dye molecules to TiO2 through an amide linkage for use as photoanodes (PAs)
      in dye-sensitized solar cells (DSSCs). Attenuated total reflectance-Fourier
      transform infrared spectroscopy (ATR-FTIR) confirms the surface chemistry between
      the TiO2 and dye. The photovoltaic efficiency of DSSCs with covalently linked dye
      is very similar (6-7%) to that of traditionally prepared DSSCs prepared by direct
      immersion when both have similar dye coverage. Importantly, the efficiency of PAs
      with covalently linked dye did not change after storage for more than 60 days in
      air, whereas the traditionally prepared PAs decreased dramatically after 1 day
      and lost most of their efficiency after a week. FTIR and UV-vis characterization
      of the dye suggests that covalent linkage improves stability by preventing the
      loss of the thiocyanato ligands and/or tetrabutylammonium cations on the dye. PAs
      with covalently linked dye are also more stable toward water, acid, heat, and UV
      light compared to traditionally prepared PAs and are more stable compared to
      other modified PAs with dye attached through electrostatic or hydrogen-bonding
      interactions. 

PMID- 24087980
TI  - Effect of using bedside leukocyte filter on pulmonary functions in patients with
      thalassemia major.
AB  - In settings of limited health resources, using leukocyte-filtered blood is
      limited to patients with leukocyte-mediated complications. The aim of this study
      was to determine the patterns of lung dysfunction among patients with beta
      thalassemia major (BTM) after the application of the leukostop filter during
      transfusion for a period of 6 months. The study included 30 patients with
      transfusion-dependent BTM divided into two groups according to the use of
      leukocyte filter. Group I included 15 patients with BTM allocated to use the
      leukocyte filter before each blood transfusion for 6 months and group II included
      15 patients with BTM using nonleukocyte-filtered blood. Patients with history of
      airway disease and smokers were excluded. Chest X-ray and pulmonary function
      tests (PFT) using spirometry were done for each patient at baseline and after the
      use of the leukocyte filter for 6 months. No significant difference was found at
      baseline PFTs in both groups, the distribution of obstructive pulmonary disease
      significantly improved in group I in the postfilter evaluation, P < 0.05, however
      no change in pulmonary disease distribution in group II. A statistical
      significance improvement in forced vital capacity (FVC), forced expiratory volume
      in 1st second (FEV1) and FEV1/FVC in postfilter evaluation, while in group II a
      decline in FEV1, FVC, and no significant change in FEV1/FVC ratio. There was no
      correlation between serum ferritin and PFT results. CONCLUSION: Pulmonary
      function abnormalities, although subclinical is not an infrequent finding in
      patients with BTM; leukofiltred blood may improve PFT.

PMID- 24087981
TI  - Neuromuscular taping for the upper limb in Cerebral Palsy: A case study in a
      patient with hemiplegia.
AB  - OBJECTIVE: To assess quantitatively the effects of Neuromuscular Taping (NMT) on
      the upper limb in a female child with left hemiplegia, due to Cerebral Palsy
      (CP). METHODS: The patient underwent NMT on cervical level, shoulder and hand
      only of the plegic upper limb, followed by physical therapy. Kinematic data of
      upper limbs during reaching task were collected before (PRE) and after 2 weeks of
      treatment (POST). RESULTS: After the intervention, the affected limb improved in
      terms of movement duration, Average Jerk and Number of Unit Movements indices,
      indicating a faster, smoother and less segmented movement. Improvements appeared
      at the ranges of motion of the upper limb joints, both at shoulder and elbow
      joints. No significant changes were globally displayed for the unaffected arm.
      CONCLUSION: NMT seems to be a promising intervention for improving upper limb
      movement in patients with CP. Further investigations are certainly needed to
      assess effectively the effects of the intervention in this pathological state.

PMID- 24087982
TI  - Uranium association with iron-bearing phases in mill tailings from Gunnar,
      Canada.
AB  - The speciation of uranium was studied in the mill tailings of the Gunnar uranium
      mine (Saskatchewan, Canada), which operated in the 1950s and 1960s. The nature,
      quantification, and spatial distribution of uranium-bearing phases were
      investigated by chemical and mineralogical analyses, fission track mapping,
      electron microscopy, and X-ray absorption near edge structure (XANES) and
      extended X-ray absorption fine structure (EXAFS) spectroscopies at the U LIII
      edge and Fe K-edge. In addition to uranium-containing phases from the ore,
      uranium is mostly associated with iron-bearing minerals in all tailing sites.
      XANES and EXAFS data and transmission electron microscopy analyses of the samples
      with the highest uranium concentrations (~400-700 mg kg(-1) of U) demonstrate
      that uranium primarily occurs as monomeric uranyl ions (UO2(2+)), forming inner
      sphere surface complexes bound to ferrihydrite (50-70% of the total U) and to a
      lesser extent to chlorite (30-40% of the total U). Thus, the stability and
      mobility of uranium at the Gunnar site are mainly influenced by
      sorption/desorption processes. In this context, acidic pH or alkaline pH with the
      presence of UO2(2+)- and/or Fe(3+)-complexing agents (e.g., carbonate) could
      potentially solubilize U in the tailings pore waters. 

PMID- 24087983
TI  - On the nature of the apparent free energy of inserting amino acids into membrane
      through the translocon.
AB  - The nature of the biological free energy scale (DeltaGapp), obtained from
      translocon mediated insertion studies, has been a major puzzle and the subject of
      major controversies. Part of the problem has been the complexity of the insertion
      process that discouraged workers from considering the feasible kinetics schemes
      and left the possible impression that DeltaGapp presents some simple partition.
      Here we extend and clarify our recent analysis of the insertion problem using
      well-defined kinetics schemes and a free energy profile. We point out that
      although the rate constants of some steps are far from being obvious, it is
      essential to consider explicitly such schemes in order to advance in analyzing
      the meaning of DeltaGapp. It is then shown that under some equilibrium conditions
      the kinetics scheme leads to a simple formula that allows one to relate DeltaGapp
      to the actual free energy of partitioning between the water, the membrane, and
      the translocon. Other options are also considered (including limits with
      irreversible transitions that can be described by linear free energy
      relationships (LFERs)). It is concluded that it is unlikely that a kinetics plus
      thermodynamic based analysis can lead to a result that identifies DeltaGapp with
      the partition between the membrane and the translocon. Thus, we argue that unless
      such analysis is presented, it is unjustified to assume that DeltaGapp
      corresponds to the membrane translocon equilibrium or to some other arbitrary
      definition. Furthermore, we point out that the presumption that it is sufficient
      to just calculate the PMF for going from the translocon (TR) to the membrane and
      then to assume irreversible diffusive motion to water and for further entrance to
      the membrane is not a valid analysis. Overall, we point out that it is important
      to try to relate DeltaGapp to a well-defined kinetics scheme (regardless of the
      complication of the system) in order to determine whether the energies of
      inserting positively charged residues to the membrane are related to the
      corresponding DeltaGapp. It is also suggested that deviations from our simple
      formula for equilibrium conditions can help in identifying and analyzing kinetics
      barriers. 

PMID- 24087984
TI  - Evaluation of thermophysical properties of ionic liquids with polar solvent: a
      comparable study of two families of ionic liquids with various ions.
AB  - In this work, we explore and compare the role of the ion effect on the
      thermophysical properties of two families of ionic liquids (ILs), namely, tetra
      alkyl ammonium cation [R4N](+) with hydroxide [OH](-) anion and 1-alkyl-3-methyl
      imidazolium cation [amim](+) with different anions (chloride, methyl sulfate, and
      tetrafluoroborate), with polar solvent such as dimethylsulfoxide (DMSO) in the
      temperature range from 25 to 40  degrees C and over the whole concentration range
      of ILs. Two families of ILs, namely, tetramethyl ammonium hydroxide [(CH3)4N][OH]
      (TMAH), tetraethyl ammonium hydroxide [(C2H5)4N][OH] (TEAH), tetrapropyl ammonium
      hydroxide [(C3H7)4N][OH] (TPAH), and tetrabutyl ammonium hydroxide [(C4H9)4N][OH]
      (TBAH) from ammonium-based ILs and 1-ethyl-3-methylimidazolium chloride
      [Emim][Cl], 1-ethyl-3-methylimidazolium methylsulfate [Emim][MeSO4], 1-butyl-3
      methylimidazolium tetrafluoroborate [Bmim][BF4], and 1-butyl-3-methylimidazolium
      chloride ([Bmim][Cl]) from imidazolium family of ILs, are used in the present
      study. To address the molecular interactions of ILs with DMSO, densities (rho),
      ultrasonic sound velocities (u), and viscosities (eta) have been measured over
      the entire composition range and at four temperatures, 25, 30, 35, and 40 
      degrees C, under atmospheric pressure. From these experimental data, the excess
      molar volume (V(E)), the deviation in isentropic compressibility (Deltakappas),
      and the deviation in viscosity (Deltaeta) were calculated and were adequately
      correlated by using the Redlich-Kister polynomial equation. The measured and
      predicted data were interpreted on the basis of intermolecular interactions and
      structural effects between like and unlike molecules upon mixing. The hydrogen
      bonding features between ammonium-based ILs and DMSO were analyzed using
      molecular modeling program by HyperChem 7. 

PMID- 24087985
TI  - Academic difficulties and occupational outcomes of adult survivors of childhood
      leukemia who have undergone allogeneic hematopoietic stem cell transplantation
      and fractionated total body irradiation conditioning.
AB  - We studied academic and employment outcomes in 59 subjects who underwent
      allogeneic hematopoietic stem cell transplantation (a-HSCT) with fractionated
      total body irradiation (fTBI) for childhood leukemia, comparing them with, first,
      the general French population and, second, findings in 19 who underwent a-HSCT
      with chemotherapy conditioning. We observed an average academic delay of 0.98
      years among the 59 subjects by Year 10 of secondary school (French class
      Troisieme), which was higher than the 0.34-year delay in the normal population (P
      < .001) but not significantly higher than the delay of 0.68 years in our cohort
      of 19 subjects who underwent a-HSCT with chemotherapy. The delay was dependent on
      age at leukemia diagnosis, but not at fTBI. This delay increased to 1.32 years by
      the final year of secondary school (Year 13, Terminale) for our 59 subjects
      versus 0.51 years in the normal population (P = .0002), but did not differ
      significantly from the 1.08-year delay observed in our cohort of 19 subjects. The
      number of students who received their secondary school diploma (Baccalaureate)
      was similar to the expected rate in the general French population for girls
      (observed/expected = 1.02) but significantly decreased for boys (O/E = 0.48; CI:
      95%[0.3-0.7]). Compared with 13.8% of the general population, 15.3% of the cancer
      survivors received no diploma (P = NS). Reported job distribution did not differ
      significantly between our cohort of childhood cancer survivors and the general
      population except that more female survivors were employed in intermediate-level
      professional positions. Academic difficulties after fTBI are common and their
      early identification will facilitate educational and professional achievement. 

PMID- 24087986
TI  - Synthesis of Janus compounds for the recognition of G-U mismatched nucleobase
      pairs.
AB  - The design and synthesis of two Janus-type heterocycles with the capacity to
      simultaneously recognize guanine and uracyl in G-U mismatched pairs through
      complementary hydrogen bond pairing is described. Both compounds were
      conveniently functionalized with a carboxylic function and efficiently attached
      to a tripeptide sequence by using solid-phase methodologies. Ligands based on the
      derivatization of such Janus compounds with a small aminoglycoside, neamine, and
      its guanidinylated analogue have been synthesized, and their interaction with Tau
      RNA has been investigated by using several biophysical techniques, including UV
      monitored melting curves, fluorescence titration experiments, and (1)H NMR. The
      overall results indicated that Janus-neamine/guanidinoneamine showed some
      preference for the +3 mutated RNA sequence associated with the development of
      some tauopathies, although preliminary NMR studies have not confirmed binding to
      G-U pairs. Moreover, a good correlation has been found between the RNA binding
      affinity of such Janus-containing ligands and their ability to stabilize this
      secondary structure upon complexation. 

PMID- 24087987
TI  - Stable DNA aggregation by removal of counterions.
AB  - Negatively charged DNA can form extremely stable complexes with positively
      charged ions. These counterions are very difficult to remove from DNA; therefore,
      little is known about DNA behavior in their deficiency. We investigated whether
      removal of counterions from the strongly bound counterion layer would elicit any
      novel DNA properties or behaviors. In order to remove the tightly bound
      counterions, we used dialysis against deionized water in the presence of a strong
      (0.6 kV/cm) electric field. The electric field promoted the dissociation of the
      DNA-counterion complexes, while dialysis facilitated irreversible partitioning of
      counterions and DNA. Counterintuitively, when deprived of counterions, DNA
      precipitated from the solution into amorphous aggregates. The aggregates remained
      stable even when the electric field was turned off but readily redissolved when
      counterions were reintroduced. The phenomenon is likely explained by attraction
      of like-charged DNA polyions due to entropic-stabilization of condensed
      counterion layers. 

PMID- 24087988
TI  - Kinetic study of the OH + glyoxal reaction: experimental evidence and
      quantification of direct OH recycling.
AB  - The kinetics of the OH + glyoxal, (HCO)2, reaction have been studied in N2 and
      N2/O2 bath gas from 5-80 Torr total pressure and 212-295 K, by monitoring the OH
      decay via laser induced fluorescence (LIF) in excess (HCO)2. The following rate
      coefficients, kOH+(HCO)2 = (9.7 +/- 1.2), (12.2 +/- 1.6), and (15.4 +/- 2.0) *
      10(-12) cm(3) molecule(-1) s(-1) (where errors represent a combination of
      statistical errors at the 2sigma level and estimates of systematic errors) were
      measured in nitrogen at temperatures of 295, 250, and 212 K, respectively. Rate
      coefficient measurements were observed to be independent of total pressure but
      decreased following the addition of O2 to the reaction cell, consistent with
      direct OH recycling. OH yields, PhiOH, for this reaction were quantified
      experimentally for the first time as a function of total pressure, temperature,
      and O2 concentration. The experimental results have been parametrized using a
      chemical scheme where a fraction of the HC(O)CO population promptly dissociates
      to HCO + CO, the remaining HC(O)CO either dissociates thermally or reacts with O2
      to give CO2, CO, and regenerate OH. A maximum PhiOH of (0.38 +/- 0.02) was
      observed at 212 K, independent of total pressure, suggesting that ~60% of the
      HC(O)CO population promptly dissociates upon formation. Qualitatively similar
      behavior is observed at 250 K, with a maximum PhiOH of (0.31 +/- 0.03); at 295 K,
      the maximum PhiOH decreased further to (0.29 +/- 0.03). From the parametrization,
      an OH yield of PhiOH = 0.19 is calculated for 295 K and 1 atm of air. It is shown
      that the proposed mechanism is consistent with previous chamber studies. While
      the fits are robust, experimental evidence suggests that the system is influenced
      by chemical activation and cannot be fully described by thermal rate
      coefficients. The atmospheric implications of the measurements are briefly
      discussed. 

PMID- 24087989
TI  - Efficacy of low molecular weight heparin in patients with acute exacerbation of
      chronic obstructive pulmonary disease receiving ventilatory support.
AB  - INTRODUCTION: Severe and acute exacerbation of chronic obstructive pulmonary
      disease (COPD) is associated with a high mortality. Since COPD is an airway
      inflammatory disease, and heparin has shown anti-inflammatory effects in previous
      studies, we evaluated the clinical effect of low molecular weight heparin (LMWH;
      nadroparin) in COPD patients admitted into the hospital due to acute
      exacerbations. METHODS: Sixty-six patients admitted to the intensive care unit
      (ICU) were randomly divided into control group (n = 33) and LMWH group (n = 33).
      The control group received conventional treatment, including oxygen therapy (non
      invasive or conventional mechanical ventilation), anti-infection, atomization
      expectorant, spasmolysis, anti-asthmatics, and nutritional support. The LMWH
      group received the same treatment plus LMWH for 1 week. The levels of plasma C
      reactive protein, interleukin-6, and fibrinogen were measured. The main outcomes
      were duration of mechanical ventilation, length of ICU stay, and hospital stay.
      RESULTS: There were no significant differences between the groups with respect to
      demographics, severity of illness, and gas exchange variables. The levels of
      plasma C-reactive protein, interleukin-6, and fibrinogen were significantly
      decreased in the LMWH group. LMWH significantly reduced the mean duration of
      mechanical ventilation (6.6 days vs. 3.8 days; p < 0.01), the length of ICU stay
      (8.5 days vs. 5.6 days; p < 0.01) and hospital stay (14.3 days vs. 11.3 days; p <
      0.01). CONCLUSIONS: The addition of LMWH to standard therapy benefits COPD
      patients with acute exacerbation.

PMID- 24087990
TI  - Preparation of well-defined dendrimer encapsulated ruthenium nanoparticles and
      their evaluation in the reduction of 4-nitrophenol according to the Langmuir
      Hinshelwood approach.
AB  - This study discusses the preparation of various sized dendrimer encapsulated
      ruthenium nanoparticles (RuDEN) with the use of the generation 4 (G4), generation
      5 (G5), and generation 6 (G6) hydroxyl-terminated poly(amidoamine) (PAMAM-OH)
      dendrimers as templating agents. The size of the nanoparticles ranges from 1.1 to
      2.2 nm. These catalysts were fully characterized using UV/vis spectrophotometry,
      infrared (IR) spectroscopy, and transmission electron microscopy (TEM). The RuDEN
      catalysts were evaluated in the reduction of 4-nitrophenol (4NP) in the presence
      of sodium borohydride (BH4(-)) for various concentrations of either. The kinetic
      data obtained were modeled to the Langmuir-Hinshelwood equation. The model allows
      the relation of the apparent rate constant to the total surface area S of the
      nanoparticle, the kinetic constant k which is related to the rate-determining
      step, and the adsorption constants K(4NP) and K(BH4) for 4NP and borohydride,
      respectively. These parameters were calculated for each of the RuDENs, proving
      the Langmuir-Hinshelwood model to be suitable for the kinetic evaluation of
      RuDENs in the catalytic reduction of 4NP.

PMID- 24087992
TI  - Structure-activity analysis of flavonoids: direct and indirect antioxidant, and
      antiinflammatory potencies and toxicities.
AB  - Flavonoids are secondary plant products that are well represented in healthy
      diets because of ingestion of fruit, vegetables, herbs, and teas. Increased
      consumption is correlated with decreased risks of cardiovascular disease, cancer,
      and other chronic diseases. Certain flavonoids confer direct antioxidant
      protection to cells, others induce enzymes that protect cells against oxidative
      and other insults ("indirect antioxidants"), and others appear to be protective
      by both mechanisms. Hydroxylated flavones manifest substantial direct antioxidant
      activity but do not effectively induce cytoprotective enzymes. Methoxylated
      flavones that potently induce cytoprotective enzymes were evaluated to elucidate
      the structural prerequisites for effective chemoprotective agents: protecting
      healthy cells with minimal collateral toxicity. Flavones and flavanones
      methoxylated at the 5-position of the A-ring were among the most potent inducers
      of the cytoprotective NAD(P)H:quinone-oxidoreductase 1 (NQO1) in 3 different cell
      lines. Other flavones were equally potent inducers, but more toxic. Flavanones
      contain no Michael reaction center, yet some are potent inducers of NQO1, have
      low cytotoxicity, and inhibit LPS-stimulated iNOS activity, which suggests a
      redox mechanism of action rather than the Keap1/Nrf2/ARE mechanism by which so
      many of the classic inducers operate. Evaluation in vivo will reveal whether
      differential protective advantages support their possible evaluation in a cancer
      prevention setting. 

PMID- 24087991
TI  - Parent perceptions of early prognostic encounters following children's severe
      traumatic brain injury: 'locked up in this cage of absolute horror'.
AB  - OBJECTIVE: Little guidance exists for discussing prognosis in early acute care
      with parents following children's severe traumatic brain injury (TBI). Providers'
      beliefs about truth-telling can shape what is said, how it is said and how
      providers respond to parents. METHODS: This study was part of a large qualitative
      study conducted in the US (42 parents/37 families) following children's moderate
      to-severe TBI (2005-2007). Ethnography of speaking was used to analyse interviews
      describing early acute care following children's severe TBI (29 parents/25
      families). RESULTS: Parents perceived that: (a) parents were disadvantaged by
      provider delivery; (b) negative outcome values dominated some provider's talk;
      (c) truth-telling involves providers acknowledging all possibilities; (d) framing
      the child's prognosis with negative medical certainty when there is some
      uncertainty could damage parent-provider relationships; (e) parents needed to
      remain optimistic; and (f) children's outcomes could differ from providers' early
      acute care prognostications. CONCLUSION: Parents blatantly and tacitly revealed
      their beliefs that providers play an important role in shaping parent reception
      of and synthesis of prognostic information, which constructs the family's ability
      to cope and participate in shared decision-making. Negative medical certainty
      created a fearful or threatening environment that kept parents from being fully
      informed.

PMID- 24087993
TI  - [Comparison of data from registries of acute coronary syndromes RECORD and RECORD
      2: management of patients and its results in noninvasive hospitals].
AB  - Positive changes are declared to occur during recent years in management of
      hospitalized patients with acute coronary syndromes (ACS) in Russia. Most of
      these changes are related to availability of invasive treatment. But considerable
      portion of patients (pts) are still treated in hospitals without facilities for
      invasive myocardial revascularization (noninvasive hospitals - NIHs). Aim of this
      study was to compare some characteristics of management of ACS in NIHs which
      participated in ACS registries RECORD (2007-2008, 8 NIHs from 6 cities; n=381)
      and RECORD-2 (2009-2011, 3 NIHs from 3 cities, n=680). Results. Groups of pts
      recruited in these NIHs had similar mean age and portion of women (67.6 and 66.5
      years, 51.1 and 53.1 % in RECORD-2 and RECORD, respectively, p=0.64). Time from
      symptoms onset to hospitalization was shorter in RECORD-2 (3.2 vs 4.1 hours for
      ST-elevation [STE], =0.03; 4.0 vs 6.5 hours for non ST elevation [NSTE] ACS,
      <0.0001). Among RECORD-2 NSTEACS pts more had ST depressions (50.6 vs 28.7%,
      <0.0001), high risk of death according to GRACE score (39.1 vs 20.9 %, <0.0001),
      but less Killip class >II (15.0 vs 21.6%, p=0.025). No such differences existed
      among STEACS pts. Thrombolysis was more often used in RECORD-2 (62.6 vs 34.1%,
      <0.0001). Both STEACS and NSTEACS RECORD-2 pts more often received clopidogrel
      (63.5 vs 18.8%, p<0.0001, and 41.6 vs 11.1%, <0.0001, respectively). More NSTEACS
      RECORD-2 pts were given parenteral anticoagulants (93.4 vs 80.4%, <0.0001), low
      molecular weight heparins (23.4 vs. 3.4%, <0.0001) and fondaparinux (10.4 vs
      0.7%, <0.0001), but still in 20% of NSTEACS RECORD-2 pts unfractionated heparin
      was given subcutaneously. Twenty RECORD-2 pts (2.9%) were transferred to invasive
      hospital but none during first 24 hours. There were no significant differences
      between registers in hospital mortality (20.0 vs 21.2%, =0.84; 4.2 vs 2.7%, =0.24
      in STE and NSTE ACS pts of RECORD-2 and RECORD, respectively). Conclusions.
      Despite some improvement in management of pts occurring in 2-3 years NIHs
      mortality in STEACS remained very high. Numerically higher mortality in NSTEACS
      could be partially attributed to higher risk of RECORD-2 pts. 

PMID- 24087994
TI  - [Regional experience of conducting registry of acute coronary syndrome].
AB  - Since 2008 Cardiological Dispensary of Khanty-Mansi Autonomous Okrug "Center of
      Diagnostics and Cardiovascular Surgery" has been participating in Rossiysky
      Registry of Acute Coronary Syndrome. In this paper we present some of the results
      on the use of percutaneous coronary interventions, time intervals, characterizing
      urgent medical aid to patients with acute coronary syndrome, rate of
      complications, and mortality. 

PMID- 24087995
TI  - [The role of multifocal atherosclerosis in realization of new cardiovascular
      complications during one year after non ST-elevation acute coronary syndrome].
AB  - STUDY AIM: to assess prognostic value of multifocal atherosclerosis (MFA)
      relative to risk of new cardiovascular catastrophes in patients with non ST
      elevation acute coronary syndrome (NSTEACS) during one year follow-up. MATERIAL
      AND METHODS: atients with NSTEACS (n=266) subjected to coronary angiography and
      color duplex scanning of peripheral arteries (PA) were included in this study.
      Presence of "end points" (cardiovascular death, stroke, myocardial infarction,
      unstable angina, decompensation of heart failure) was assessed after one year of
      follow-up. RESULTS: aximal GRACE score was revealed in patients with MFA
      (combined involvement of coronary arteries [CA] and peripheral arteries [PA]).
      Compared with patients without involvement of CA or PA unfavorable outcomes were
      2 times more frequent in the presence of lesions only in CA, 3 times more
      frequent in the presence of combination of lesions in CA and PA stenoses <50%, 4
      times more frequent in the presence of lesions in CA and PA stenosis >50%.
      Percutaneous coronary intervention at the hospital stage led to 3.3-fold
      improvement of long term prognosis in patients with single vessel CA involvement
      and absence of stenoses in PA, and to 1.8 fold improvement - in patients with
      multivessel CA involvement and PA stenoses >50%. CONCLUSION: resence of even
      nonsignificant PA stenoses in patients with NSTEACS predetermined high rate of
      unfavorable events during one year follow-up.

PMID- 24087996
TI  - [Predictive significance of integral indices in the diagnosis of ischemic heart
      disease. Dependence on the possibility to perform exercise stress test].
AB  - Integral indices are used for optimization of verification of coronary heart
      disease (CHD). When due to some reason it is not possible to carry out stress
      tests their pretest analogues gain special importance. The latter proposition has
      been confirmed in this study. 

PMID- 24087997
TI  - [Coronary artery disease in Russia: todays reality evidenced by the international
      CLARIFY registry].
AB  - This paper presents the specific features of clinical manifestation and treatment
      of coronary heart disease (CHD) in the Russian Federation and compares them to
      the data from other countries participating in the international CLARIFY
      (ProspeCtive observational LongitudinAl RegIstry oF patients with stable coronary
      arterY disease) Registry. In accordance with the exclusion and inclusion
      criteria, 2249 patients from 43 Russian regions were included in the Registry.
      Russian patients were younger and had a higher prevalence of risk factors and
      comorbidities, compared to patients from other countries. In particular, the
      former more often had cardiovascular disease in family history, smoked (20.9% vs
      11.8%; p<0.0001), and had dyslipidemia (77.8% vs 74.6%; p<0.0001) or hypertension
      (79.6% vs 70.3%; p<0.0001).They also had a higher heart rate (p<0.0001). ). While
      the incidence of myocardial infarction, based on medical history, was
      significantly higher than in patients from other countries (78.3% vs 58.4%;
      p<0.0001), percutaneous coronary intervention (PCI) was performed 2.5 times less
      often. Particularly striking differences were observed for the prevalence of
      stable angina and heart failure, which was, respectively, 4.0 and 7.8 times
      higher in Russian patients, despite the fact that the prescription frequency was
      similar in the Russian Federation and other countries. These findings should
      focus Russian doctors attention on the potential ways to solve the problem of
      "national features" in the treatment of stable CHD. 

PMID- 24087998
TI  - [Prophylactic use of VFS in patients with coronary artery disease in the
      perioperative coronary artery bypass grafting].
AB  - Tachyarrhythmias (TA) - dangerous postoperative complications of coronary artery
      bypass grafting, threatening the lives of patients and found, according to
      different authors, in 13-40% of cases. VFS - an antiarrhythmic drug that belongs
      to a class 1C, is effective in the treatment and prevention of a variety of
      cardiac arrhythmias. The aim of the work was to study the clinical efficacy of
      VFS CHD patients with a history of tachyarrhythmias during the perioperative
      period of coronary bypass surgery, as well as its comparison with other
      antiarrhythmic drug (amiodarone). Clinical efficacy was evaluated in 218 patients
      with coronary heart disease at baseline with a history of tachyarrhythmia
      (paroxysmal atrial fibrillation or premature ventricular high grade (IV and V
      class on classification of Lown B. and Wolf M. in the modification of Ryan M.).
      Shown that the VFS is more effective than amiodarone, both in paroxysmal atrial
      fibrillation and ventricular arrhythmias when high gradation. 

PMID- 24087999
TI  - [Coenzyme q10 in complex therapy of patients with ischemic heart disease].
AB  - The paper contains results of assessment of clinical efficacy and safety of
      coenzyme Q10 in patients with ischemic heart disease. Coenzyme Q10 (60 mg/day for
      8 weeks) added to basic treatment of patients with stable class II-III angina
      significantly improved clinical status of these patients without clinically
      significant side effects. 

PMID- 24088000
TI  - [Variants of remodeling of left ventricular myocardium in patients with arterial
      hypertension and disturbances of carbohydrate metabolism].
AB  - AIM: to study special characteristics of left ventricular (LV) myocardial
      remodeling in patients with arterial hypertension (AH) and disturbances of
      carbohydrate metabolism. MATERIAL AND METHODS: We examined 241 patients with 1-2
      degree AH and comparable age and sex: 100 patients had type 2 diabetes mellitus
      (DM) (group 1), 41 had impaired glucose tolerance (IGT) (group 2), 100 patient
      had normal glucose tolerance (group 3). Examination included anthropometric and
      laboratory studies, echocardiography. RESULTS: Concentric LV hypertrophy was
      found in 34, 14.6 and 6% of patients in groups 1, 2, and 3, respectively. There
      were no significant differences between groups by other variants of myocardial
      remodeling. Disturbances of LV diastolic function were more frequent in groups 1
      (89%) and 2 (82.9%) compared with group 3 (57%). CONCLUSION: Concentric LV
      hypertrophy was more frequent in patients with AH and type 2 DM.

PMID- 24088001
TI  - [Oxygen supply to the brain in chronic disturbances of cerebral circulation in
      patients with pathology of brachiocephalic arteries].
AB  - We assessed objective parameters of cerebral oxygen supply in 469 patients with
      multifocal atherosclerosis, hemodynamically significant lesions in
      brachiocephalic arteries in dependence on degree of severity of vascular cerebral
      insufficiency according to A.V. Pokrovsky classification of chronic disturbances
      of cerebral circulation. Comparison of clinical classification with parameters of
      cerebral oximetry and level of cerebral tolerance to hypoxia allowed to
      characterize pathophysiological mechanisms of cerebral oxygen metabolism, what
      was important for determination of risk of surgical treatment and postoperative
      prognosis. 

PMID- 24088002
TI  - [Clinical course and outcomes of myocardial infarction in women].
AB  - We selected all case histories of patients living in the area served by the
      Syktyvkar policlinic #3 and treated in Republican Cardiological Dispensary in
      2003-2009 with diagnosis of myocardial infarction (MI). Data on survival of
      patients after MI (mean duration of follow-up 4.6 years) was derived from
      information on date and cause of death of patients obtained from statistical
      office of the policlinic. Overall we analyzed data on 778 patients (46.3% women,
      mean age 63.7 years). For detection of independent factors related to lethal
      outcome we used binary logistic regression, for assessment of survival we used
      Kaplan-Meier method and Cox regression model of proportional hazards. From
      positions of gender differences we assessed pharmacoepidemiology of MI, efficacy
      of thrombolytic therapy, determined factors of hospital and long term mortality.
      No increase of risk of hospital or long term mortality associated with female sex
      was revealed by multifactorial analysis. Greatest prognostic significance in
      relation to unfavorable outcome irrespective of patients sex was established for
      the following factors: age, severity of MI course, severity of renal dysfunction.
      In acute period of MI in addition to these factors we revealed unfavorable
      influence of hyperglycemia and protective role of preceding hypertensive disease.

PMID- 24088003
TI  - [The use of implantable devices for long-term monitoring of cardiac rhythm after
      surgical treatment of atrial fibrillation in patients with ischemic heart
      disease].
AB  - We present in this paper experience of the use of implantable devices for long
      term monitoring of cardiac rhythm after one stage operation of coronary artery
      bypass grafting (CABG) and radiofrequency ablation of atrial fibrillation (AF)
      source and results of a prospective randomized study, in which we included
      patients (n=95) with persistent AF and ischemic heart disease. These patients
      were randomized into 3 groups: with radiofrequency isolation of ostia of
      pulmonary veins (group 1, n=31), radiofrequency modified mini-maze procedure
      (group 2, n=30); CABG without AF elimination (control group 3, n=34). Implantable
      devices Reveal XT were used in 53 patients (21, 25, and 7 in groups 1, 2, and 3,
      respectively). According to data obtained with these devices AF was absent in
      86.7, 95.6, 53%, and in 80, 86.2, 44.1% of patients in groups 1, 2, 3 after 1 and
      2 years after operation, respectively). In 24% of patients Reveal devices also
      registered asymptomati-c arrhythmias. The use of implantable devices for
      monitoring of rhythm allowed to detect such arrhythmia and to provide timely
      correction of therapy. 

PMID- 24088005
TI  - [Informativeness of genetic factors for optimization of personalized therapy with
      clopidogrel].
AB  - We studied occurrence of allele variants *1, *2, *3, and *17 of CYP2C19 gene and
      polymorphic variants of ABCB1 gene in clopidogrel treated patients from West
      Siberian and Far Eastern regions and determined contribution of these
      polymorphisms to laboratory efficacy of clopidogrel. In dependence on magnitude
      of change of platelet aggregation we distinguished groups of patients with
      different sensitivity to clopidogrel. We found association between polymorphic
      variant CYP2C19*2 with changes of platelet aggregation after administration of
      clopidogrel. An additional group of patients with augmented platelet aggregation
      after administration of clopidogrel was detected. There was no correlation
      between the latter effect and any of studied polymorphisms. 

PMID- 24088004
TI  - [Effect of an educational program on effectiveness and safety of anticoagulant
      therapy in patients with prostheses of cardiac valves].
AB  - We analyzed effectiveness and safety of anticoagulant therapy in patients with
      prostheses of cardiac valves at the background of educational program and without
      special training. We revealed positive effect of educational program during
      participation in which in 80 cases (67.8%) patients determined international
      normalized ratio every month and in 50 of them (62,5%) level of hypocoagulation
      corresponded to target range (p=0.001). At the background of educational program
      rate of thrombotic complications was 2.73% per patient year, at the background of
      no educational program - 4.90% per patient year (p=0.040) while rates of
      hemorrhagic complications were 2.73 and 7.20% per patient year, respectively
      (p=0.002). 

PMID- 24088006
TI  - [Combination therapy of arterial hypertension: focus on the treatment of women].

PMID- 24088007
TI  - [Alcoholic heart disease].
AB  - We present in this review contemporary views on pathogenesis of alcoholic
      cardiomyopathy. Alcoholic cardiomyopathy has features of dilated cardiomyopathy
      and is manifested by increased volume and hypertrophy of the left ventricle,
      diminished contractile capacity, and when decompensated - by lowering of cardiac
      output. Pathogenic action of alcohol on cardiomyocytes leads to activation of
      apoptosis, dysfunction of intracellular organelles, alterations of the system of
      myofilaments, disorder of intracellular homeostasis of calcium. Ethanol
      metabolite acetaldehyde, products of minor pathway of catecholamine metabolism,
      changes in the endocannabinoid system, and activation of processes of lipid
      peroxidation all contribute to the myocardial damage. The basis of pathogenesis
      of alcoholic cardiomyopathy constitute proliferation of microperoxisomes and
      disbalance between acyloxidase and catalase leading to accumulation of hydrogen
      peroxide inside myocytes. 

PMID- 24088008
TI  - [Successful treatment of bradyarrhythmia associated with obstructive sleep apnea
      syndrome by continuous positive airway pressure].
AB  - Obstructive Sleep Apnea Syndrome (OSAS) is an additional independent factor of
      growth of cardiovascular mortality. Special role disturbances of respiration
      during sleep play in development of nocturnal cardiac arrhythmias. Approaches to
      correction of OSAS associated nocturnal bradyarrhythmias have substantially
      changed during recent years. We present report of a clinical case in which we
      detected relation of nocturnal bradyarrhythmias to OSAS. Adequate correction of
      OSAS by continuous positive airway pressure therapy resulted in complete
      elimination of bradyarrhythmias during night time. This allowed to avoid
      implantation of permanent pacemaker. 

PMID- 24088009
TI  - Incorporation of a rotavirus vaccine into the national immunisation schedule in
      the United Kingdom: a review.
AB  - INTRODUCTION: Rotavirus, the commonest cause of severe acute gastroenteritis in
      infants and young children worldwide, imposes a large health and economic burden
      on the British society, accounting for an estimated 14,300 hospitalisations and
      133,000 general practitioner consultations each year among children aged < 5
      years in England and Wales alone. Following a tender process, an attenuated human
      rotavirus vaccine, Rotarix (GlaxoSmithKline Biologicals, Belgium), was introduced
      into the UK childhood immunisation programme in 2013. AREA COVERED: This article
      provides a review of the product profile of the Rotarix vaccine for use in the
      national immunisation programme in the UK from an expert perspective. EXPERT
      OPINION: This single G1P[8] strain-based human rotavirus vaccine has demonstrated
      high efficacy in preventing severe rotavirus gastroenteritis in the first 3 years
      of life in middle- and high-income countries. In countries that have adopted
      rotavirus vaccine in childhood immunisation programmes, indirect benefits (herd
      protection) have been observed among older, unvaccinated children and adults.
      When the first dose is administered between 6 and 14 weeks of age and the last
      dose by 24 weeks of age, Rotarix carries a small risk of intussusception within
      the week of vaccination. However, this small risk may at most result in a
      negligible population attributable risk at the end of the first year of life.
      Overall, the rotavirus immunisation programme is expected to provide substantial
      health benefits to the UK population.

PMID- 24088010
TI  - Therapeutic horse riding improves cognition, mood arousal, and ambulation in
      children with dyspraxia.
AB  - OBJECTIVES: The objectives of this study were to evaluate the effects of the
      physical motion of a horse (riding therapy) combined with the audiovisual
      perception of this motion on a group of children with dyspraxia in terms of
      cognition, mood arousal, and gait variability. DESIGN: The study design was a
      pretest/post-test. SETTINGS/LOCATION: The study was conducted at the Fettercairn
      Youth Horse Project, Fettercairn, Tallaght, Dublin. SUBJECTS: Forty (40) children
      ranging from 6 to 15 years of age with a primary diagnosis of dyspraxia were the
      study subjects. INTERVENTIONS: Children meeting inclusion criteria participated
      in six 30-minute horse-riding sessions and two 30-minute audiovisual screening
      sessions. OUTCOME MEASURES: A Standard Progressive Matrices test (also known as
      the Ravens test) was used to measure aspects of general intelligence. A Childhood
      Depression Inventory (CDI) questionnaire was used to assess cognitive, affective,
      and behavioral signs of depression. A GAITRite Pressure Mapping System analyzed
      foot function and gait variability by measuring single and double support, cycle
      time, cadence, toe in/out, and stride length. RESULTS: Significant improvements
      were evident on the Ravens test and the CDI by the end of the study period. The
      amount of both single and double support required while completing the walking
      task also was significantly reduced. Improvements were visible on toe in/out
      values, cycle time, and cadence. Changes in stride length did not reach
      statistical significance. CONCLUSIONS: These findings support the theory that
      riding therapy and/or the perception of beat-based rhythms, as experienced by the
      rider on the horse, stimulates cognition, mood, and gait parameters. In addition,
      the data also pointed to the potential value of an audiovisual approach to equine
      therapy.

PMID- 24088011
TI  - Side effects of interferon therapy in adolescent melanoma.

PMID- 24088012
TI  - Novel type of protein chip for multiplex detection of autoantibodies.
AB  - Evaluation of: Akada J, Kamei S, Ito A et al. A new type of protein chip to
      detect hepatocellular carcinoma-related autoimmune antibodies in the sera of
      hepatitis C virus-positive patients. Proteome Sci. 11(1), 33 (2013). Unlocking
      the proteome and delivering biomarkers to the clinic will be critical for early
      and improved diagnosis and prognosis. Conventional protein microarrays have
      evolved as a promising proteomic technology with great potential for protein
      expression profiling in health and disease. In this study, Akada et al. explore a
      new type of protein chip, interfaced with a dual-color fluorescence-based read
      out, for screening of autoantibodies in serum. Uniquely, the recombinant antigens
      were microarray adapted by molecular design to contain a five-cysteine tag for
      immobilization and green fluorescent protein for detection (color 1). The
      engineered antigens were immobilized on in-house-designed maleimide-incorporated
      diamond-like carbon substrates and subsequently heat treated in a solution of
      denaturing and reducing agents before any specifically bound serum autoantibodies
      were detected (color 2). The authors used a 4-plex array targeting hepatocellular
      carcinoma-related autoantibodies in the sera of hepatitis C virus-positive
      patients as model system to demonstrate proof-of-concept. 

PMID- 24088014
TI  - The role of intact oleosin for stabilization and function of oleosomes.
AB  - Lipid storage in plants is achieved among all plant species by formation of
      oleosomes, enclosing oil (triacylglycerides) in small subcellular droplets. Seeds
      are rich in this pre-emulsified oil to provide a sufficient energy reservoir for
      growing. The triacylglyceride core of the oleosomes is surrounded by a
      phospholipid monolayer containing densely packed proteins called oleosins. They
      are anchored in the triacylglycerides core with a hydrophobic domain, while the
      hydrophilic termini remain on the surface. These specialized proteins are
      expressed during seed development and maturation. Particularly, they play a major
      role in the stabilization and function of oleosomes. To better understand the
      importance of oleosins for oleosome stabilization, enzymatic digestion of
      oleosins was performed. This made it possible to compare and correlate changes in
      the molecular structure of oleosins and changing macroscopic properties of
      oleosomes. Tryptic digestion cleaves the hydrophilic part of the oleosins, which
      is accompanied by a loss of secondary structures as evidenced by Fourier
      transform infrared and sum frequency generation spectra. After digestion, the
      ability of oleosins to stabilize oil-water or air-water interfaces was lost. The
      surface charge and the associated aggregation behavior of oleosomes are governed
      by interactions typical of proteins before digestion and by interactions typical
      of phospholipids after digestion. 

PMID- 24088015
TI  - Individual differences in personality as a function of degree of handedness:
      consistent-handers are less sensation seeking, more authoritarian, and more
      sensitive to disgust.
AB  - Prior research indicates that consistent-handedness is associated with decreased
      access to right hemisphere processing and consequent decreased cognitive
      flexibility. Handedness differences on three dimensions of personality related to
      cognitive flexibility were investigated. Experiment 1 found that consistent
      handedness was associated with decreased sensation seeking. Experiment 2 found
      that consistent-handedness was associated with increased Right Wing
      Authoritarianism. Experiment 3 found that consistent-handedness was associated
      with increased sensitivity to disgust. Prior research has shown associations
      between decreased sensation seeking, increased authoritarianism, and increased
      disgust sensitivity, and consistent-handedness appears to underlie all of these
      associations. Personality researchers are encouraged to include handedness as a
      factor in analyses, as failure to do so can lead to systematic mis-estimation of
      sex differences due to the over-representation of females among consistent
      handers. 

PMID- 24088013
TI  - Direct measurement of the Mn(II) hydration state in metal complexes and
      metalloproteins through 17O NMR line widths.
AB  - Here we describe a simple method to estimate the inner-sphere hydration state of
      the Mn(II) ion in coordination complexes and metalloproteins. The line width of
      bulk H2(17)O is measured in the presence and absence of Mn(II) as a function of
      temperature, and transverse (17)O relaxivities are calculated. It is demonstrated
      that the maximum (17)O relaxivity is directly proportional to the number of inner
      sphere water ligands (q). Using a combination of literature data and experimental
      data for 12 Mn(II) complexes, we show that this method provides accurate
      estimates of q with an uncertainty of +/-0.2 water molecules. The method can be
      implemented on commercial NMR spectrometers working at fields of 7 T and higher.
      The hydration number can be obtained for micromolar Mn(II) concentrations. We
      show that the technique can be extended to metalloproteins or complex:protein
      interactions. For example, Mn(II) binds to the multimetal binding site A on human
      serum albumin with two inner-sphere water ligands that undergo rapid exchange
      (1.06 * 10(8) s(-1) at 37  degrees C). The possibility of extending this
      technique to other metal ions such as Gd(III) is discussed. 

PMID- 24088016
TI  - Authorizing multiple chemical passwords by a combinatorial molecular keypad lock.
AB  - A combinatorial fluorescent molecular sensor operates as a highly efficient
      molecular security system. The ability of a pattern-generating molecule to
      process diverse sets of chemical inputs, discriminate among their concentrations,
      and form multivalent and kinetically stable complexes is demonstrated as a
      powerful tool for processing a wide range of chemical "passwords" of different
      lengths. This system thus indicates the potential for obtaining unbreakable
      combination locks at the molecular scale. 

PMID- 24088017
TI  - Fine tuning of reactive oxygen species homeostasis regulates primed immune
      responses in Arabidopsis.
AB  - Selected stimuli can prime the plant immune system for a faster and stronger
      defense reaction to pathogen attack. Pretreatment of Arabidopsis with the
      chemical agent beta-aminobutyric acid (BABA) augmented H2O2 and callose
      production after induction with the pathogen-associated molecular pattern (PAMP)
      chitosan, or inoculation with the necrotrophic fungus Plectosphaerella
      cucumerina. However, BABA failed to prime H2O2 and callose production after
      challenge with the bacterial PAMP Flg22. Analysis of Arabidopsis mutants in
      reactive oxygen species (ROS) production (rbohD) or ROS scavenging (pad2, vtc1,
      and cat2) suggested a regulatory role for ROS homeostasis in priming of chitosan-
      and P. cucumerina-inducible callose and ROS. Moreover, rbohD and pad2 were both
      impaired in BABA-induced resistance against P. cucumerina. Gene expression
      analysis revealed direct induction of NADPH/respiratory burst oxidase protein D
      (RBOHD), gamma-glutamylcysteine synthetase 1 (GSH1), and vitamin C defective 1
      (VTC1) genes after BABA treatment. Conversely, ascorbate peroxidase 1 (APX1)
      transcription was repressed by BABA after challenge with chitosan or P.
      cucumerina, probably to provide a more oxidized environment in the cell and
      facilitate augmented ROS accumulation. Measuring ratios between reduced and
      oxidized glutathione confirmed that augmented defense expression in primed plants
      is associated with a more oxidized cellular status. Together, our data indicate
      that an altered ROS equilibrium is required for augmented defense expression in
      primed plants. 

PMID- 24088018
TI  - Biological activity of the tzs gene of nopaline Agrobacterium tumefaciens GV3101
      in plant regeneration and genetic transformation.
AB  - Agrobacterium tumefaciens has been widely used in plant genetic transformation.
      Hormone-encoding genes residing in the T-DNA region have been removed, resulting
      in disarmed Agrobacterium strains that are used in various transformation
      experiments. Nopaline Agrobacterium strains, however, carry another hormone gene,
      trans-zeatin synthesizing (tzs), that codes for trans-zeatin in the virulence
      region of the tumor-inducing plasmids. We investigated the activity and function
      of the tzs gene of a nopaline Agrobacterium sp. strain GV3101 in plant in vitro
      regeneration. Leaf explants of tobacco and Nicotiana benthamiana co-cultured with
      strain GV3101 exhibited active shoot regeneration in media without added plant
      growth regulators. On medium without plant growth regulators, transgenic shoots
      were also induced from explants co-cultured with GV3101 containing a binary
      vector. Enzyme-linked immunosorbent assay showed that cell-free extracts of
      Agrobacterium sp. strain GV3101 culture contained the trans-zeatin at 860
      ng/liter. Polymerase chain reaction using tzs-specific primers showed that the
      tzs gene was present in strain GV3101 but not in other Agrobacterium strains. The
      study showed that the tzs gene in GV3101 was actively expressed, and that trans
      zeatin produced in the Agrobacterium strain can promote plant shoot regeneration.

PMID- 24088022
TI  - Natural wetlands are efficient at providing long-term metal remediation of
      freshwater systems polluted by acid mine drainage.
AB  - This study describes the first long-term (14-year) evaluation of the efficacy of
      an established (>100 years) natural wetland to remediate highly acidic mine
      drainage (AMD). Although natural wetlands are highly valued for their
      biodiversity, this study demonstrates that they also provide important ecosystem
      service functions through their ability to consistently and reliably improve
      water quality by mitigating AMD. The Afon Goch river flows from Parys Mountain
      copper mine via a natural wetland, and was the major source of Zn and Cu
      contamination to the Irish Sea. Prior to 2003 the wetland received severe acidic
      metal contamination and retained a large proportion of the contamination (55, 64,
      and 37% in dissolved Fe, Zn, and Cu) leading to a greatly reduced metal flow to
      the Irish Sea. Reduced wetland loadings midway through the sampling period led to
      a reduction of metals by 83-94% and a pH increase from 2.7 to 5.5, resulting in
      long-term improvements in the downstream benthic invertebrate community. High
      root metal accumulation by the dominant wetland plant species and the association
      of acidophilic bacteria in the wetland rhizosphere indicate that multiple
      interacting processes provide an efficient and self-sustaining system to
      remediate AMD. 

PMID- 24088021
TI  - The role of basic amino acid surface clusters on the collagenase activity of
      cathepsin K.
AB  - Cathepsin K is a highly potent collagenase in osteoclasts and is responsible for
      bone degradation. We have previously demonstrated that its unique collagenolytic
      activity is modulated by glycosaminoglycans that form high molecular weight
      complexes with the protease. However, mutational analysis of a specific
      glycosaminoglycan-cathepsin K binding site only led to a 60% reduction of the
      collagenolytic activity suggesting additional glycosaminoglycan binding sites or
      other determinants controlling this activity. We identified eight cathepsin K
      specific arginine/lysine residues that form three positively charged clusters at
      the bottom part of the protease opposing the active site. These residues are
      highly conserved among mammalian, avian, and reptilian cathepsin K orthologues
      and to a lesser degree in amphibian and fish specimens. Mutational analysis of
      these residues revealed an approximately 50% reduction of the collagenolytic
      activity when the basic amino acids in cluster 2 (K103, K106, R108, R111) were
      mutated into alanine residues and resulted in a 100% loss of this activity when
      the mutations were expanded into cluster 3 (K122, R127). Cluster 1 mutations
      (K77, R79) had no effect. A partial rescue effect was observed when the
      hexamutant variant was combined with three mutations in the previously identified
      glycosaminoglycan binding site (N190, K101, L195K) indicating the relevance of at
      least two independent interaction sites. Amino acid substitutions in all sites
      had no effect on the catalytic efficacy of the protease variants as reflected in
      their unaltered peptidolytic and gelatinolytic activities and their overall
      protein stabilities. This study suggests that the basic amino acid clusters in
      cathepsin K are involved in alternative glycoasaminoglycan binding sites, play
      other roles in the formation of collagenolytically active protease complexes, or
      contribute in a yet unknown manner to the specific binding to collagen.

PMID- 24088023
TI  - Edaravone for acute stroke: Meta-analyses of data from randomized controlled
      trials.
AB  - AIMS: To assess the effectiveness of edaravone for acute stroke including
      ischemic stroke and intracerebral hemorrhage (ICH). METHODS: We identified
      randomized controlled trials with comprehensive searches and performed systematic
      reviews according to the Cochrane methods of systematical reviews. RESULTS:
      Edaravone can reduce the rate of death or long-term disability significantly for
      acute ischemic stroke (AIS) (RR = 0.65; 95%CI, 0.48 to 0.89, p = 0.007). However,
      sensitivity analysis yielded a different result. Edaravone can also improve the
      short-term neurological impairment of AIS (MD = 7.09; 95%CI, 5.12 to 9.05, p <
      0.00001), and ICH (MD = -4.32; 95%CI, -5.35 to -3.29, p < 0.00001). CONCLUSIONS:
      Edaravone is beneficial in improving neurological impairment resulting from AIS
      and ICH. However, currently there is no enough convincing evidence that edaravone
      reduces death or long-term disability for AIS and ICH.

PMID- 24088024
TI  - Electro-(de)wetting on superhydrophobic surfaces.
AB  - Usually, electrowetting on superhydrophobic surfaces (EWOSS) is generated by
      application of an alternating current signal and often leads to droplet
      impalement into the structuration. To avoid this phenomenon, superhydrophobic
      surfaces must show robustness to high pressure. Otherwise, an external energy has
      to be applied to dewet the droplet from the structuration. We present, in this
      article, an original approach to actuate liquid droplets via a modulated EWOSS
      signal (MEWOSS). This technique allows the dewetting of the droplet due to
      periodic vibrations induced by the electrowetting actuation. In that case, it is
      possible to investigate a larger range of superhydrophobic surfaces under EWOSS
      without droplet impalement. Three different superhydrophobic surfaces, showing
      different degrees of impalement under EWOSS, are investigated and compared using
      this MEWOSS technique. 

PMID- 24088026
TI  - On chip guidance and recording of cardiomyocytes with 3D mushroom-shaped
      electrodes.
AB  - The quality of the recording and stimulation capabilities of multielectrode
      arrays (MEAs) substantially depends on the interface properties and the coupling
      of the cell with the underlying electrode area. The purpose of this work was the
      investigation of a three-dimensional nanointerface, enabling simultaneous
      guidance and recording of electrogenic cells (HL-1) by utilizing nanostructures
      with a mushroom shape on MEAs. 

PMID- 24088025
TI  - Three different profiles: early socio-communicative capacities in typical Rett
      syndrome, the preserved speech variant and normal development.
AB  - BACKGROUND AND AIMS: This is the first study aiming to compare pre-diagnostic
      socio-communicative development of a female with typical Rett syndrome (RTT), a
      female with the preserved speech variant of RTT (PSV) and a control toddler.
      METHODS: We analysed 1275 min of family videos at the participants' age between 9
      and 24 months and used the Inventory of Potential Communicative Acts (IPCA) to
      delineate their repertoires of communicative forms and functions. RESULTS: The
      results revealed different profiles for the three different conditions. The
      repertoire of communicative gestures and (pre)linguistic vocalizations was most
      comprehensive in the control toddler, followed by the female with PSV and the
      female with RTT. CONCLUSION: These findings contribute to the growing knowledge
      about early developmental abnormalities in RTT. In order to define distinctive
      profiles for typical and atypical RTT and evaluate their specificity, a larger
      body of evidence is needed.

PMID- 24088027
TI  - Multiplexed detection and imaging of intracellular mRNAs using a four-color
      nanoprobe.
AB  - Simultaneous detection and imaging of multiple intracellular biomarkers hold
      great promise for early cancer detection. Here, we introduce a four-color
      nanoprobe that can simultaneously detect and image four types of mRNAs in living
      cells. The nanoprobe composed of gold nanoparticles functionalized with a dense
      shell of molecular beacons, which can identify multiple intracellular mRNA
      transcripts. It shows rapid response, high specificity, nuclease stability, and
      good biocompatibility. Intracellular experiments indicate that the nanoprobe
      could effectively distinguish cancer cells from their normal cells, even some
      mRNAs are overexpressed in normal cells. Moreover, it can identify the changes of
      the expression levels of mRNA in living cells. The current strategy could provide
      more-accurate information for early cancer detection and availably avoid false
      positive results. 

PMID- 24088029
TI  - Serum vitamin B12 and folate concentrations and the effect of the Mediterranean
      diet on vulnerable populations.
AB  - Low vitamin B12 and folate levels in expectant mothers may lead to low stores in
      babies. The aim of this study was to determine the frequencies of vitamin B12 and
      folate deficiencies in pregnant women and neonates, and to assess the effect of
      maternal vitamin status on babies' vitamin levels in the Aegean region of Turkey,
      where the Mediterranean diet (mainly fresh fruits and vegetables) is adopted. We
      studied 72 pregnant women and their singleton-term babies. Venous blood samples
      of expectant mothers were collected 1 h before delivery and cord blood of babies
      were obtained at birth. The mean vitamin B12 in maternal and cord blood serum was
      163.1 +/- 72.0 pg/mL and 146.2 +/- 102.5 pg/mL, and the mean folate, 9.8 +/- 4.8
      ng/mL and 15.8 +/- 3.8 ng/mL, respectively. There were statistically significant
      correlation between maternal and cord blood serum vitamin B12 (r = 0.61, P = .04)
      and folate levels (r = 0.65, P < .001). 70.8% of the mothers and 83.9% of the
      babies were vitamin B12 deficient (<200 pg/mL). Neither group showed folate
      deficiency. The mean level of vitamin B12 in mothers significantly varied by the
      type of diet (241.6 (72.1) pg/mL versus 155.9 (68.2) pg/mL; P = .012). Vitamin
      B12 deficiency in pregnant women and neonates may be a public health problem in
      our community. The Mediterranean diet in these vulnerable groups may be an
      aggravating factor for vitamin B12 deficiency. Prenatal screening of all
      expectant mothers, prenatal supplementation of vitamin B12, and an increase in
      animal-source food intake may improve expectant mother's vitamin B12 level. 

PMID- 24088028
TI  - Structural studies on dinuclear ruthenium(II) complexes that bind
      diastereoselectively to an antiparallel folded human telomere sequence.
AB  - We report DNA binding studies of the dinuclear ruthenium ligand
      [{Ru(phen)2}2tpphz](4+) in enantiomerically pure forms. As expected from previous
      studies of related complexes, both isomers bind with similar affinity to B-DNA
      and have enhanced luminescence. However, when tested against the G-quadruplex
      from human telomeres (which we show to form an antiparallel basket structure with
      a diagonal loop across one end), the LambdaLambda isomer binds approximately 40
      times more tightly than the DeltaDelta, with a stronger luminescence. NMR studies
      show that the complex binds at both ends of the quadruplex. Modeling studies,
      based on experimentally derived restraints obtained for the closely related
      [{Ru(bipy)2}2tpphz](4+), show that the LambdaLambda isomer fits neatly under the
      diagonal loop, whereas the DeltaDelta isomer is unable to bind here and binds at
      the lateral loop end. Molecular dynamics simulations show that the DeltaDelta
      isomer is prevented from binding under the diagonal loop by the rigidity of the
      loop. We thus present a novel enantioselective binding substrate for antiparallel
      basket G-quadruplexes, with features that make it a useful tool for quadruplex
      studies. 

PMID- 24088030
TI  - Bone formation in calvarial defects by injectable nanoparticular scaffold loaded
      with stem cells.
AB  - OBJECTIVE: Calcium phosphates are one of biomaterials that are used for bone
      regeneration. In this study, calcium phosphate nanoparticles such as
      hydroxyapatite (HA)/fluorapatite (FA),with chitosan gel filled with unrestricted
      somatic stem cells (USSCs) were used for healing calvarial bone in rat model.
      METHODS: The healing effects of these injectable scaffolds, with and without stem
      cells, in bone regeneration were investigated by computed tomography (CT)
      analysis and pathology assays after 28 days of grafting. RESULTS: The results of
      CT analysis showed that bone regeneration on the scaffolds, and the amounts of
      regenerated new bone for USSC scaffold were significantly greater than the
      scaffold without cell and untreated controls. CONCLUSION: Therefore, the
      combination of scaffold especially with USSC could be considered as a useful
      method for bone regeneration.

PMID- 24088033
TI  - Excitation wavelength dependence of excited state intramolecular proton transfer
      reaction of 4'-N,N-diethylamino-3-hydroxyflavone in room temperature ionic
      liquids studied by optical Kerr gate fluorescence measurement.
AB  - Excited state intramolecular proton transfer reactions (ESIPT) of 4'-N,N
      diethylamino-3-hydroxyflavone (DEAHF) in ionic liquids have been studied by
      steady-state and time-resolved fluorescence measurements at different excitation
      wavelengths. Steady-state measurements show the relative yield of the tautomeric
      form to the normal form of DEAHF decreases as excitation wavelength is increased
      from 380 to 450 nm. The decrease in yield is significant in ionic liquids that
      have cations with long alkyl chains. The extent of the decrease is correlated
      with the number of carbon atoms in the alkyl chains. Time-resolved fluorescence
      measurements using optical Kerr gate spectroscopy show that ESIPT rate has a
      strong excitation wavelength dependence. There is a large difference between the
      spectra at a 200 ps delay from different excitation wavelengths in each ionic
      liquid. The difference is pronounced in ionic liquids having a long alkyl chain.
      The equilibrium constant in the electronic excited state obtained at a 200 ps
      delay and the average reaction rate are also correlated with the alkyl chain
      length. Considering the results of the steady-state fluorescence and time
      resolved measurements, the excitation wavelength dependence of ESIPT is explained
      by state selective excitation due to the difference of the solvation, and the
      number of alkyl chain carbon atoms is found to be a good indicator of the effect
      of inhomogeneity for this reaction. 

PMID- 24088034
TI  - Structural characterization of 1,1,3,3-tetramethylguanidinium chloride ionic
      liquid by reversible SO2 gas absorption.
AB  - A unique new ionic liquid-gas adduct solid state compound formed between 1,1,3,3
      tetramethylguanidinium chloride ([tmgH]Cl) and sulfur dioxide has been
      characterized by X-ray diffraction and Raman spectroscopy. The structure contains
      SO2 molecules of near normal structure kept at their positions by Cl-S
      interactions. The crystals belong in the orthorhombic system, space group Pbcn,
      with unit cell dimensions of a = 15.6908(10) A, b = 9.3865(6) A, and c =
      14.1494(9) A, angles alpha = beta = gamma = 90 degrees , and Z = 8 at 120 K. The
      [tmgH]Cl has a very high absorption capacity of nearly 3 mol of SO2 per mol of
      [tmgH]Cl at 1 bar of SO2 and at room temperature. However, part of the absorbed
      SO2 was liberated during the crystallization, probably because the crystal only
      accommodates one molecule of SO2 per [tmgH]Cl. The nature of the high absorption
      capacity of [tmgH]Cl as well as of the homologous compounds with bromide and
      iodide are discussed. Some of these salts may prove useful as reversible
      absorbents of SO2 in industrial flue gases. 

PMID- 24088035
TI  - Effect of magnetic hyperthermia on the structure of biofilm and cellular
      viability of a food spoilage bacterium.
AB  - This work evaluated the effect of magnetic hyperthermia (MH) on planktonic cells
      and biofilms of a major food spoilage bacterium Pseudomonas fluorescens and its
      performance compared to a conventional direct heating (DH) technique. The results
      showed that MH had a greater and faster bactericidal effect, promoting a
      significant reduction in cell viability (>=3 Log CFU) in planktonic and biofilm
      cells, and leading to a complete eradication of planktonic cells at 55  degrees C
      (after only ~8 min). Accordingly, when comparing the same final temperatures, MH
      was more harmful to the integrity of cell membranes than DH, as observed in
      confocal laser scanning microscope images. Additionally, scanning electron
      microscope images revealed that exposure to MH had promoted modifications of the
      bacterial cell surface as well as of the structure of the biofilm. These results
      present the possibility of using MH out of the biomedical field as a potential
      disinfection method in food-related environments. 

PMID- 24088036
TI  - Long-term effectiveness of intralesional triamcinolone acetonide therapy in
      orofacial granulomatosis: an observational cohort study.
AB  - BACKGROUND: It has been suggested that intralesional triamcinolone injections
      represent a safe and effective therapeutic strategy in controlling the permanent
      disfiguring swelling of orofacial granulomatosis (OFG). However, robust
      supporting evidence is lacking, due to the variable and inconsistent design of
      available studies. OBJECTIVES: To investigate whether a standardized regimen of
      intralesional triamcinolone has beneficial long-term effects on orofacial
      swelling of OFG. We also studied potential associations with a number of
      prognostic factors. METHODS: We designed a retrospective observational study of a
      homogeneous cohort of 22 well-phenotyped patients with OFG. The primary outcome
      was defined as a statistically significant decrease in post-treatment disease
      severity. Statistically significant association with prognostic factors was the
      secondary outcome. Statistical analysis included Wilcoxon signed-rank tests and
      logistic regression. RESULTS: Compared with pretreatment, there were
      statistically significant decreases in disease severity scores at all time points
      until 48 months post-treatment (P < 0.01). Logistic regression analysis showed
      there was no independent prognostic variable of statistical significance (P >
      0.05). The majority of patients (14/22, 63.6%) received one course of
      intralesional triamcinolone and did not experience disease recurrence. The mean
      disease-free period after the first course of intralesional therapy was 28.9 +/-
      18 months (95% confidence interval 28.7-29.1). No adverse effects were reported.
      CONCLUSIONS: This is the first study to have employed robust cohort methodology
      and sound statistics to demonstrate long-term effectiveness of intralesional
      triamcinolone in controlling the disfiguring swelling of OFG. Because of
      limitations inherent in observational studies, further research in the form of
      randomized case-control trials is needed to confirm the present findings.

PMID- 24088037
TI  - Respiratory viral detection and small airway inflammation in lung tissue of
      patients with stable, mild COPD.
AB  - BACKGROUND: Viral respiratory tract infections are implicated in the pathogenesis
      of chronic obstructive pulmonary disease (COPD). In lung tissue specimens from
      patients with stable, mild COPD and from control smokers without airflow
      obstruction, we determined the prevalence and load of nucleic acid from common
      respiratory viruses and concomitant inflammation of small airways measuring less
      than 2-mm in diameter. METHODS: Frozen lung tissue obtained from patients with
      stable, mild COPD (n = 20) and control subjects (n = 20) underwent real-time
      quantitative PCR (qPCR) for 13 respiratory viruses, and quantitative histology
      for inflammation of small airways. The two groups were compared for viral
      prevalence and load, and airway inflammation. The relationship between viral load
      and airway inflammatory cells was also analyzed. RESULTS: Viral nucleic acid were
      detected in lung tissue of 18/40 (45.0%) of the individuals studied and included
      seven co-infections that were characterized by a "dominant virus" contributing to
      most of the total measured viral load. Lung tissue of COPD patients had a
      significantly higher prevalence of viral nucleic acid (particularly influenza A
      virus), and increased inflammation of small airways by macrophages and
      neutrophils versus controls. In qPCR-positive individuals, linear regression
      analysis showed a direct correlation between viral load and airway neutrophils,
      and between influenza A virus load and airway macrophages. CONCLUSION: The lung
      tissue of patients with stable, mild COPD has a higher prevalence and load of
      respiratory viruses versus non-obstructed control subjects, and increased
      inflammation of small airways. Respiratory viruses may represent potential
      targets in COPD patient management.

PMID- 24088038
TI  - Reorientation-induced spectral diffusion in vibrational sum-frequency-generation
      spectroscopy.
AB  - There is a growing appreciation that dynamic processes play an important role in
      determining the line shape in surface-selective, nonlinear spectroscopies such as
      vibrational sum-frequency-generation (VSFG). Here we analyze the influence that
      reorientation can have on VSFG spectra when the vibrational transition frequency
      is a function of orientation. Under these circumstances, reorientation-induced
      spectral diffusion (RISD) causes the underlying spectral line shape to become
      time dependent. Unlike previously reported mechanisms through which reorientation
      can contribute to the VSFG signal, RISD influences the line shape regardless of
      the degree of polarization of the Raman transition that is probed. We assess the
      impact of RISD on VSFG spectra using a model system of liquid acetonitrile at a
      silica interface. Comparison of delay-time-dependent VSFG spectra with
      simulations that employ static line shapes suggests that RISD contributes
      substantially to the spectra, particularly at delay times that are comparable to
      or greater than the probe pulse duration. The observed behavior is in qualitative
      agreement with a two-state RISD model that uses orientational distributions
      determined from previous molecular dynamics simulations. 

PMID- 24088039
TI  - Differences in participation based on self-esteem in power and manual wheelchair
      users on a university campus: a pilot study.
AB  - OBJECTIVES: To examine the relationship of self-esteem and wheelchair type with
      participation of young adult manual and power wheelchair users with diverse
      physical disabilities. DESIGN: Cross-sectional survey study. SETTING: Large
      University Campus. PARTICIPANTS: A convenience sample of college students (N =
      39) with self-reported physical disabilities who are full time wheelchair users
      (>40 per week) and are two or more years post illness or injury. INTERVENTIONS:
      Not applicable. MAIN OUTCOME MEASURES: The Rosenberg Self-Esteem Scale was used
      to measure self-esteem, and the Craig Handicap Assessment and Reporting Technique
      was used to measure participation. RESULTS: Self-esteem correlated highly with
      cognitive independence (CI) (r = 0.58), mobility (r = 0.67) and social
      integration (SI) (r = 0.52). Use of manual wheelchair was significantly related
      to higher levels of CI and mobility while longer use of any wheelchair (power or
      manual) was significantly associated with higher levels of mobility and SI. In
      addition higher self-esteem independently predicted a significant proportion of
      the variance in CI, mobility and SI, while type of wheelchair predicted a
      significant proportion of the variance in CI (p < 0.005). CONCLUSIONS: High self
      esteem was found to be the strongest predictor of participation in a population
      of young adults with mobility limitations. Better understanding of the factors
      influencing participation may help to facilitate new interventions to minimize
      the disparities between persons with disabilities and their able bodied peers.
      Implication for Rehabilitation A total of 46.8% of wheelchair users report the
      desire for increased community participant but face significant barriers. The
      type of wheelchair has been identified as having a large impact on participation.
      This study found self-esteem to be the strongest predictor of participation,
      which is notable because self-esteem is a characteristic that is potentially
      modifiable with treatment.

PMID- 24088040
TI  - Next-generation sequencing for clinical diagnostics.

PMID- 24088042
TI  - The ACA and high-deductible insurance--strategies for sharpening a blunt
      instrument.

PMID- 24088041
TI  - Clinical whole-exome sequencing for the diagnosis of mendelian disorders.
AB  - BACKGROUND: Whole-exome sequencing is a diagnostic approach for the
      identification of molecular defects in patients with suspected genetic disorders.
      METHODS: We developed technical, bioinformatic, interpretive, and validation
      pipelines for whole-exome sequencing in a certified clinical laboratory to
      identify sequence variants underlying disease phenotypes in patients. RESULTS: We
      present data on the first 250 probands for whom referring physicians ordered
      whole-exome sequencing. Patients presented with a range of phenotypes suggesting
      potential genetic causes. Approximately 80% were children with neurologic
      phenotypes. Insurance coverage was similar to that for established genetic tests.
      We identified 86 mutated alleles that were highly likely to be causative in 62 of
      the 250 patients, achieving a 25% molecular diagnostic rate (95% confidence
      interval, 20 to 31). Among the 62 patients, 33 had autosomal dominant disease, 16
      had autosomal recessive disease, and 9 had X-linked disease. A total of 4
      probands received two nonoverlapping molecular diagnoses, which potentially
      challenged the clinical diagnosis that had been made on the basis of history and
      physical examination. A total of 83% of the autosomal dominant mutant alleles and
      40% of the X-linked mutant alleles occurred de novo. Recurrent clinical
      phenotypes occurred in patients with mutations that were highly likely to be
      causative in the same genes and in different genes responsible for genetically
      heterogeneous disorders. CONCLUSIONS: Whole-exome sequencing identified the
      underlying genetic defect in 25% of consecutive patients referred for evaluation
      of a possible genetic condition. (Funded by the National Human Genome Research
      Institute.).

PMID- 24088043
TI  - PLS3 mutations in X-linked osteoporosis with fractures.
AB  - Plastin 3 (PLS3), a protein involved in the formation of filamentous actin (F
      actin) bundles, appears to be important in human bone health, on the basis of
      pathogenic variants in PLS3 in five families with X-linked osteoporosis and
      osteoporotic fractures that we report here. The bone-regulatory properties of
      PLS3 were supported by in vivo analyses in zebrafish. Furthermore, in an
      additional five families (described in less detail) referred for diagnosis or
      ruling out of osteogenesis imperfecta type I, a rare variant (rs140121121) in
      PLS3 was found. This variant was also associated with a risk of fracture among
      elderly heterozygous women that was two times as high as that among noncarriers,
      which indicates that genetic variation in PLS3 is a novel etiologic factor
      involved in common, multi-factorial osteoporosis. 

PMID- 24088044
TI  - Histone H3 and H4 N-terminal tails in nucleosome arrays at cellular
      concentrations probed by magic angle spinning NMR spectroscopy.
AB  - Chromatin is a supramolecular assembly of DNA and histone proteins, organized
      into nucleosome repeat units. The dynamics of chromatin organization regulates
      DNA accessibility to eukaryotic transcription and DNA repair complexes. Yet, the
      structural and dynamic properties of chromatin at high concentrations
      characteristic of the cellular environment (>~200 mg/mL) are largely unexplored
      at the molecular level. Here, we apply MAS NMR to directly probe the dynamic
      histone protein regions in (13)C,(15)N-enriched recombinant nucleosome arrays at
      cellular chromatin concentrations and conditions designed to emulate distinct
      states of DNA condensation, with focus on the flexible H3 and H4 N-terminal tails
      which mediate chromatin compaction. 2D (1)H-(13)C and (1)H-(15)N spectra reveal
      numerous correlations for H3 and H4 backbone and side-chain atoms, enabling
      identification of specific residues making up the dynamically disordered N
      terminal tail domains. Remarkably, we find that both the H3 and H4 N-terminal
      tails are overall dynamic even in a highly condensed state. This significant
      conformational flexibility of the histone tails suggests that they remain
      available for protein binding in compact chromatin states to enable regulation of
      heterochromatin. Furthermore, our study provides a foundation for quantitative
      structural and dynamic investigations of chromatin at physiological
      concentrations. 

PMID- 24088045
TI  - Short communication: Aging not gender is associated with high atazanavir plasma
      concentrations in Asian HIV-infected patients.
AB  - Physiological effects of aging make the older population more susceptible to
      adverse drug events and drug-drug interactions. We evaluated the impact of aging
      and gender on the pharmacokinetics (PK) of atazanavir/ritonavir (ATV/r) 300/100
      mg once daily (qd) in 22 well-suppressed HIV-infected patients. This was a 24-h
      intensive PK study. Subjects were HIV-1-infected adults aged >=18 years with HIV
      RNA <50 copies/ml and treated with ATV/r 300/100 mg once daily plus two
      nucleoside reverse transcriptase inhibitors (NRTIs) for at least 2 weeks.
      Atazanavir and ritonavir plasma concentrations were measured by validated high
      performance liquid chromatography (HPLC). Plasma PK parameters were calculated
      using noncompartmental methods. Since 50% of the patients were older than 42
      years, age 42 was selected as the cut-off point for the older (>42 years) group.
      Gender, weight, duration of ATV/r therapy, and proportion treated with tenofovir
      disoproxil fumarate (TDF)-containing regimens did not differ between both groups.
      Patients from the aging group had a reduced creatinine clearance (91 versus 76
      ml/min). The older group had a higher atazanavir exposure with median AUC(0-24)
      71.2 vs. 53.1 mg.h/liter, C(max) 8.5 vs. 5.5 mg/liter, and C(trough) 1.17 vs.
      0.78 mg/liter, and slower apparent clearance (3.5 vs. 4.8 liter/h). Ten patients
      (91%) from the older group and 36% from the younger group had ATV C(trough)
      levels higher than the proposed upper limit for toxicity of 0.85 mg/liter.
      Females had a lower body weight (BW) (46 versus 63 kg) than the males, but
      atazanavir concentrations in females were greater. However, in multivariate
      analysis, older age was the only significant predictor for higher atazanavir
      concentrations. Parameter estimate for age and atazanavir AUC after adjusting for
      gender and BW was 2.17 (95% CI 1.01-3.33). That is, for every year increase in
      age, AUC increases by approximately 2 mg.h/liter. Age seems to be an important
      factor influencing atazanavir pharmacokinetics. Patients from the aging group
      appeared to have higher atazanavir exposure compared to the younger group.
      Further PK explorations of ATV in the extremely aged population are warranted.

PMID- 24088046
TI  - Arsenite binding to natural organic matter: spectroscopic evidence for ligand
      exchange and ternary complex formation.
AB  - The speciation of As in wetlands is often controlled by natural organic matter
      (NOM), which can form strong complexes with Fe(III). Here, we elucidated the
      molecular-scale interaction of arsenite (As(III)) with Fe(III)-NOM complexes
      under reducing conditions. We reacted peat (40-250 MUm size fraction, 1.0 g
      Fe/kg) with 0-15 g Fe/kg at pH <2, removed nonreacted Fe, and subsequently
      equilibrated the Fe(III) complexes formed with 900 mg As/kg peat at pH 7.0, 8.4,
      and 8.8. The solid-phase speciation of Fe and As was studied by electron
      paramagnetic resonance (Fe) and X-ray absorption spectroscopy (As, Fe). Our
      results show that the majority of Fe in the peat was present as mononuclear
      Fe(III) species (RFe-C = 2.82-2.88 A), probably accompanied by small Fe(III)
      clusters of low nuclearity (RFe-Fe = 3.25-3.46 A) at high pH and elevated Fe
      contents. The amount of As(III) retained by the original peat was 161 mg As/kg,
      which increased by up to 250% at pH 8.8 and an Fe loading of 7.3 g/kg. With
      increasing Fe content of peat, As(III) increasingly formed bidentate mononuclear
      (RAs-Fe = 2.88-2.94 A) and monodentate binuclear (RAs-Fe = 3.35-3.41 A) complexes
      with Fe, thus yielding direct evidence of ternary complex formation. The ternary
      complex formation went along with a ligand exchange reaction between As(III) and
      hydroxylic/phenolic groups of the peat (RAs-C = 2.70-2.77 A). Our findings thus
      provide spectroscopic evidence for two yet unconfirmed As(III)-NOM interaction
      mechanisms, which may play a vital role in the cycling of As in sub- and anoxic
      NOM-rich environments such as peatlands, peaty sediments, swamps, or rice
      paddies. 

PMID- 24088047
TI  - Autism spectrum disorder severity as a predictor of Battelle Developmental
      Inventory - second edition (BDI-2) scores in toddlers.
AB  - OBJECTIVE: The study aimed to evaluate the relationship between the severity of
      autism spectrum disorder (ASD) symptomology and scores on the Battelle
      Developmental Inventory, Second Edition (BDI-2) in toddlers (n = 325). METHODS:
      Total scores on the BDI-2 and individual domain scores were examined to explore
      the relationship between severity of ASD and developmental quotient, impairment
      in personal-social skills, adaptive functioning, cognition, and communication.
      RESULTS: Regression analyses controlled for the impact of age and IQ on results,
      indicating that higher autism severity scores were associated with overall
      greater impairment and in the total scores and the individual domains of the BDI
      2. The domains were found to be differentially affected by severity of ASD.
      CONCLUSION: These findings suggest severity of ASD may influence symptom
      presentation. Clinical implications of study findings are discussed.

PMID- 24088048
TI  - Domain-specific physical activity and health-related quality of life in
      university students.
AB  - Information on the relationship between domain-specific physical activity (PA)
      and health-related quality of life (HRQoL) in the general population and specific
      groups is still scarce. The aim of this study was to determine the relationship
      between PA in work, transport, domestic and leisure-time domains and HRQoL among
      university students. PA and HRQoL were assessed in a random stratified sample of
      1750 university students using the International Physical Activity Questionnaire 
      long form and 12-item Short Form Health Survey, respectively. The Spearman's
      rank correlations, adjusted for age, community size, personal monthly budget,
      body mass index, smoking habits and alcohol intake ranged from -0.11 to 0.18 in
      female students and -0.29 to 0.19 in male students. Leisure-time, domestic,
      transport-related PA and total PA were positively related to HRQoL. Inverse
      correlations with HRQoL were only found for work-related PA in male students.
      Multiple linear regression analysis showed that only leisure-time PA was related
      to the Physical Summary Component score (beta = 0.08 for females and beta = 0.10
      for males, P < 0.05). Domain-specific PA levels were not significantly related to
      the Mental Component Summary score. To get a more comprehensive insight in the
      relationship between PA and HRQoL, future studies should not only analyse total
      PA levels but also domain-specific PA levels. The evidence on the positive
      relationship of leisure-time, transport and domestic PA with HRQoL can
      potentially be used to support evidence-based promotion of PA in a university
      setting, and as a hypothesis for future longitudinal studies on such potential
      causal relationships.

PMID- 24088049
TI  - Assessment of HIV/AIDS knowledge, attitudes and behaviours among students in
      higher education in Tanzania.
AB  - There is a paucity of studies that have systematically and comprehensively
      investigated the knowledge level, attitudes and the pattern of sexual behaviours
      related to HIV and AIDS in higher education settings in sub-Saharan Africa in
      general and Tanzania in particular. This study attempted to fill a void in
      knowledge. A cross-sectional descriptive design was used, employing a self
      administered questionnaire as the main data collection tool. More than 400 higher
      education students completed a questionnaire assessing their knowledge, attitudes
      and behaviours related to HIV and AIDS. About three quarters of respondents
      demonstrated comprehensive knowledge about HIV and AIDS, and the majority of
      respondents expressed positive attitudes towards people living with HIV and AIDS.
      Despite demonstrating high knowledge level about HIV and AIDS, the results show
      that sexual behaviours among students in higher education are characteristically
      risky, and do not significantly differ from youth in the general population. 

PMID- 24088050
TI  - Comparison of therapist implemented and iPad-assisted interventions for children
      with autism.
AB  - OBJECTIVE: This study compares intervention delivered by a therapist to
      intervention delivered using an iPad for two children with autism. Further, this
      study evaluates the influence of choice between the conditions. METHODS: Time on
      task, challenging behaviour, session duration and correct responses were compared
      across conditions in an alternating treatment design. The effect of choice was
      evaluated in an ABAB design. RESULTS: The iPad was associated with shorter
      intervention sessions, more time on-task and less challenging behaviour for one
      participant. There was no difference between conditions for the second
      participant. Both participants selected the iPad when given the choice and,
      although the effect of choice was modest, choosing was associated with more time
      on-task and less challenging behaviour. CONCLUSIONS: These data suggest that iPad
      assisted intervention can be as effective as therapist-implemented intervention.
      Further, even for children for whom no differences between the interventions
      exist, offering a choice may be beneficial.

PMID- 24088051
TI  - Heterotopic ossification as rare complication of hemiplegia following stroke: two
      cases.
AB  - BACKGROUND: Heterotopic ossification (HO), characterized by new bone formation in
      the periarticular regions of large joints, is frequently seen after spinal cord
      injury, traumatic brain injury, burn and trauma. It is a rare complication of
      hemiplegia following stroke, with a reported incidence of 1% or less. CASE
      REPORTS: This study reports two unusual presentations of HO: (1) A 56-year-old
      male with a history of atrial fibrillation on warfarin developed sudden-onset
      left hemiplegia. Eight months after the event, he was diagnosed with HO of the
      hip joint including both the affected and unaffected sides. (2) A 55-year-old
      female with left hemiplegia due to subarachnoid bleeding developed HO on the left
      hip joint 7 months later. In both cases, spasticity around the hip muscle groups,
      especially hip flexors, adductors and knee extensors, and limited range of motion
      accompanied by pain were present. X-ray and pelvic computed tomography revealed
      HO around the hip joints. After 4 weeks of inpatient rehabilitation, the ranges
      of hip joint motion improved, without exceeding 10 degrees  in the direction of
      flexion and rotations, and ambulation levels were wheelchair-bound for the first
      case and dependent on a cane for the second case. CONCLUSIONS: Considering the
      presented cases, it is suggested that HO should be kept in mind in the
      differential diagnosis in stroke patients presenting with spontaneous joint pain
      or limitation. The clinical importance of HO development on both the affected and
      unaffected sides in post-stroke hemiplegia is emphasized, since it may worsen the
      patient's functional status.

PMID- 24088052
TI  - Quantum confinement effects in transferrable silicon nanomembranes and their
      applications on unusual substrates.
AB  - Two dimensional (2D) semiconductors have attracted attention for a range of
      electronic applications, such as transparent, flexible field effect transistors
      and sensors owing to their good optical transparency and mechanical flexibility.
      Efforts to exploit 2D semiconductors in electronics are hampered, however, by the
      lack of efficient methods for their synthesis at levels of quality, uniformity,
      and reliability needed for practical applications. Here, as an alternative 2D
      semiconductor, we study single crystal Si nanomembranes (NMs), formed in large
      area sheets with precisely defined thicknesses ranging from 1.4 to 10 nm. These
      Si NMs exhibit electronic properties of two-dimensional quantum wells and offer
      exceptionally high optical transparency and low flexural rigidity. Deterministic
      assembly techniques allow integration of these materials into unusual device
      architectures, including field effect transistors with total thicknesses of less
      than 12 nm, for potential use in transparent, flexible, and stretchable forms of
      electronics. 

PMID- 24088053
TI  - Experimental confirmation of new drug-target interactions predicted by Drug
      Profile Matching.
AB  - We recently introduced Drug Profile Matching (DPM), a novel affinity
      fingerprinting-based in silico drug repositioning approach. DPM is able to
      quantitatively predict the complete effect profiles of compounds via probability
      scores. In the present work, in order to investigate the predictive power of DPM,
      three effect categories, namely, angiotensin-converting enzyme inhibitor,
      cyclooxygenase inhibitor, and dopamine agent, were selected and predictions were
      verified by literature analysis as well as experimentally. A total of 72% of the
      newly predicted and tested dopaminergic compounds were confirmed by tests on D1
      and D2 expressing cell cultures. 33% and 23% of the ACE and COX inhibitory
      predictions were confirmed by in vitro tests, respectively. Dose-dependent
      inhibition curves were measured for seven drugs, and their inhibitory constants
      (Ki) were determined. Our study overall demonstrates that DPM is an effective
      approach to reveal novel drug-target pairs that may result in repositioning these
      drugs. 

PMID- 24088056
TI  - Biosensors as 21st century technology for detecting genetically modified
      organisms in food and feed.

PMID- 24088057
TI  - Isomer specific product detection in the reaction of CH with acrolein.
AB  - The products formed in the reaction between the methylidene radical (CH) and
      acrolein (CH2?CHCHO) are probed at 4 Torr and 298 K employing tunable vacuum
      ultraviolet synchrotron light and multiplexed photoionization mass-spectrometry.
      The data suggest a principal exit channel of H loss from the adduct to yield
      C4H4O, accounting for (78 +/- 10)% of the products. Examination of the
      photoionization spectra measured upon reaction of both CH and CD with acrolein
      reveals that the isomeric composition of the C4H4O product is (60 +/- 12)% 1,3
      butadienal and (17 +/- 10)% furan. The remaining 23% of the possible C4H4O
      products cannot be accurately distinguished without more reliable photoionization
      spectra of the possible product isomers but most likely involves oxygenated
      butyne species. In addition, C2H2O and C3H4 are detected, which account for (14
      +/- 10)% and (8 +10, -8)% of the products, respectively. The C2H2O
      photoionization spectrum matches that of ketene and the C3H4 signal is composed
      of (24 +/- 14)% allene and (76 +/- 22)% propyne, with an upper limit of 8% placed
      on the cyclopropene contribution. The reactive potential energy surface is also
      investigated computationally, and specific rate coefficients are calculated with
      RRKM theory. These calculations predict overall branching fractions for 1,3
      butadienal and furan of 27% and 12%, respectively, in agreement with the
      experimental results. In contrast, the calculations predict a prominent CO + 2
      methylvinyl product channel that is at most a minor channel according to the
      experimental results. Studies with the CD radical strongly suggest that the title
      reaction proceeds predominantly via cycloaddition of the radical onto the C?O
      bond of acrolein, with cycloaddition to the C?C bond being the second most
      probable reactive mechanism. 

PMID- 24088058
TI  - Approaching the limit: can one DNA strand assemble into defined nanostructures?
AB  - This article reports a simple, symmetrical DNA building block (motif): a bulged
      DNA duplex consisting of two short, identical strands. Multiple copies of the
      same motif can interact with each other through T junctions. The resulting
      superstructures include predesigned 1D and 2D arrays that have been visualized by
      atomic force microscopy (AFM). 

PMID- 24088059
TI  - Monomerizing alkali-metal 3,5-dimethylbenzyl salts with tris(N, N-dimethyl-2
      aminoethyl)amine (Me6TREN): structural and bonding implications.
AB  - The series of alkali-metal (Li, Na, K) complexes of the substituted benzyl anion
      3,5-dimethylbenzyl (Me2C6H3CH2(-)) derived from 1,3,5-trimethylbenzene
      (mesitylene) have been coerced into monomeric forms by supporting them with the
      tripodal tetradentate Lewis donor tris(N,N-dimethyl-2-aminoethyl)amine,
      [N(CH2CH2NMe2)3, Me6TREN]. Molecular structure analysis by X-ray crystallography
      establishes that the cation-anion interaction varies as a function of the alkali
      metal, with the carbanion binding to lithium mainly in a sigma fashion, to
      potassium mainly in a pi fashion, with the interaction toward sodium being
      intermediate between these two extremes. This distinction is due to the heavier
      alkali-metal forcing and using the delocalization of negative charge into the
      aromatic ring to gain a higher coordination number in accordance with its size.
      Me6TREN binds the metal in a eta(4) mode at all times. This coordination
      isomerism is shown by multinuclear NMR spectroscopy to also extend to the
      structures in solution and is further supported by density functional theory
      (DFT) calculations on model systems. A Me6TREN stabilized benzyl potassium
      complex has been used to prepare a mixed-metal ate complex by a cocomplexation
      reaction with tBu2Zn, with the benzyl ligand acting as an unusual ditopic
      sigma/pi bridging ligand between the two metals, and with the small zinc atom
      relocalizing the negative charge back on to the lateral CH2 arm to give a complex
      best described as a contacted ion pair potassium zincate. 

PMID- 24088060
TI  - Assessment of axial length before and after myopic LASIK with the IOLMaster.
AB  - PURPOSE: To assess the relationship between theoretical ablation depth and axial
      length change after LASIK with the IOLMaster (Carl Zeiss Meditec, Dublin, CA).
      METHODS: Ninety-nine eyes were examined preoperatively and 1 and 3 months after
      LASIK. RESULTS: Mean +/- standard deviation (SD) spherical equivalent before
      LASIK was -4.06 +/- 1.91 diopters (D). Mean +/- SD ablation depth was 83.13 +/-
      30.31 MUm. Mean +/- SD postoperative axial length of 25.11 +/- 0.14 mm at 1 month
      was significantly shorter than mean +/- SD preoperative axial length of 25.20 +/-
      0.14 mm (P < .001) with no subsequent change thereafter (P = .450). An increase
      in ablation depth of 1 MUm led to a decrease in axial length of 0.00118 +/-
      0.00005 mm. Ablation depth correlated strongly with change in axial length
      (adjusted R(2) = 0.9039). CONCLUSIONS: The IOLMaster showed a decrease in axial
      length after LASIK that correlated well with theoretical ablation depth.

PMID- 24088061
TI  - Refractive and keratometric stability in high myopic LASIK with high-frequency
      femtosecond and excimer lasers.
AB  - PURPOSE: To evaluate safety, efficacy, ergonomy, and refractive and keratometric
      stability in high myopia LASIK procedures using a novel femtosecond and excimer
      laser surgery platform. METHODS: One hundred sixteen eyes in consecutive cases of
      high myopic LASIK ( >= -6.00 diopters [D]) with the Alcon-WaveLight FS200
      femtosecond and EX500 excimer lasers (Alcon Laboratories, Fort Worth, TX) were
      evaluated preoperatively and postoperatively for the following parameters:
      refractive error, corrected distance visual acuity, uncorrected distance visual
      acuity, spherical equivalent correction, keratometry (with Placido topography and
      Scheimpflug tomography), and refractive astigmatism. Average follow-up time was
      6.2 months (range: 3 to 12 months). RESULTS: Postoperative average refractive
      error was -0.37, -0.43, and -0.25 D for the 3-, 6-, and 12-month period, compared
      to -7.67 +/- 1.55 D preoperatively. At 3, 6, and 12 months postoperatively 94%,
      96.3%, and 100% of eyes, respectively, were within 1.0 D defocus equivalent.
      Postoperative refractive astigmatism was -0.21, -0.21, -0.13 D for the 3-, 6-,
      and 12-month period compared to -1.07 +/- 1.91 D preoperatively. The proportion
      of eyes with postoperative astigmatism within 0.25 D was 85.3%, 81.5%, and 100%,
      for the 3-, 6-, and 12-month visit, respectively. Keratometric stability was
      within 0.22 D after the 12-month visit. There was no epithelial ingrowth or
      diffuse lamellar keratitis in any case. CONCLUSIONS: Clinical outcomes with this
      technique and technology appear to be promising in high level uncorrected visual
      rehabilitation of high myopia. There was small regression potential in the sample
      evaluated.

PMID- 24088062
TI  - Understanding the regulation of estivation in a freshwater snail through iTRAQ
      based comparative proteomics.
AB  - The apple snail Pomacea canaliculata is a freshwater gastropod with a remarkable
      ability to withstand seasonal or unpredictable dry conditions by entering
      estivation. Studies of P. canaliculata using conventional biochemical and the
      individual gene approaches have revealed the expressional changes of several
      enzymes and antioxidative genes in response to estivation and arousal. In this
      study, we applied iTRAQ-coupled two-dimensional LC-MS/MS to identify and quantify
      the global protein expression during the estivation and arousal of P.
      canaliculata. A total of 1040 proteins were identified, among which 701 proteins
      were quantified and compared across four treatments (i.e., control, active
      snails; short-term estivation, 3 days of exposure to air; prolonged estivation,
      30 days of exposure to air; and arousal, 6 h after resubmergence in water)
      revealing 53 differentially expressed proteins. A comparison of protein
      expression profiles across treatments indicated that the proteome of this species
      was very insensitive to initial estivation, with only 9 proteins differentially
      expressed as compared with the control. Among the 9 proteins, the up-regulations
      of two immune related proteins indicated the initial immune response to the
      detection of stress cues. Prolonged estivation resulted in many more
      differentially expressed proteins (47 compared with short-term estivation
      treatment), among which 16 were down-regulated and 31 were up-regulated. These
      differentially expressed proteins have provided the first global picture of a
      shift in energy usage from glucose to lipid, prevention of protein degradation
      and elevation of oxidative defense, and production of purine for uric acid
      production to remove toxic ammonia during prolonged estivation in a freshwater
      snail. From prolonged estivation to arousal, only 6 proteins changed their
      expression level, indicating that access to water and food alone is not a
      necessary condition to reactivate whole-sale protein expression. A comparison
      with hibernation and diapause revealed many similar molecular mechanisms of
      hypometabolic regulation across the animal kingdom. 

PMID- 24088063
TI  - SEIPS 2.0: a human factors framework for studying and improving the work of
      healthcare professionals and patients.
AB  - Healthcare practitioners, patient safety leaders, educators and researchers
      increasingly recognise the value of human factors/ergonomics and make use of the
      discipline's person-centred models of sociotechnical systems. This paper first
      reviews one of the most widely used healthcare human factors systems models, the
      Systems Engineering Initiative for Patient Safety (SEIPS) model, and then
      introduces an extended model, 'SEIPS 2.0'. SEIPS 2.0 incorporates three novel
      concepts into the original model: configuration, engagement and adaptation. The
      concept of configuration highlights the dynamic, hierarchical and interactive
      properties of sociotechnical systems, making it possible to depict how health
      related performance is shaped at 'a moment in time'. Engagement conveys that
      various individuals and teams can perform health-related activities separately
      and collaboratively. Engaged individuals often include patients, family
      caregivers and other non-professionals. Adaptation is introduced as a feedback
      mechanism that explains how dynamic systems evolve in planned and unplanned ways.
      Key implications and future directions for human factors research in healthcare
      are discussed. 

PMID- 24088065
TI  - Advances towards the design and development of personalized non-small-cell lung
      cancer drug therapy.
AB  - INTRODUCTION: Non-small-cell lung cancer (NSCLC) subtypes are driven by specific
      genetic aberrations. For reasons such as this, there is a call for treatment
      personalization. The ability to instigate NSCLC fragmentation poses new
      methodological problems, and new 'driver' molecular aberrations are being
      discovered at an unprecedented pace. AREAS COVERED: This article describes the
      clinical development of epidermal growth factor-tyrosine kinase inhibitors (EGFR
      TKIs) and crizotinib for EGFR-mutant and anaplastic lymphoma kinase (ALK)
      rearranged NSCLC. Further, the authors briefly describe the emerging molecular
      targets in NSCLC, in terms of both rationale for therapeutic targeting and
      strategies, for clinical development. EXPERT OPINION: Target identification and
      validation in NSCLC still requires considerable effort, as not all of the
      molecular alterations are clear 'drivers' nor can they be efficiently targeted
      with available drugs. However, 50% of the NSCLC cases are without clear-defined
      molecular aberrations. Clinical trial methodology will need to develop novel
      paradigms for targeted drug development, aiming at the validation of an ideal
      'biology-to-trial' approach. Despite significant challenges, a truly
      'personalized' approach to NSCLC therapy appears to be within our reach.

PMID- 24088066
TI  - Red-light-controllable liquid-crystal soft actuators via low-power excited
      upconversion based on triplet-triplet annihilation.
AB  - A red-light-controllable soft actuator has been achieved, driven by low-power
      excited triplet-triplet annihilation-based upconversion luminescence (TTA-UCL).
      First, a red-to-blue TTA-based upconversion system with a high absolute quantum
      yield of 9.3 +/- 0.5% was prepared by utilizing platinum(II)
      tetraphenyltetrabenzoporphyrin (PtTPBP) as the sensitizer and 9,10
      bis(diphenylphosphoryl)anthracene (BDPPA) as the annihilator. In order to be
      employed as a highly effective phototrigger of photodeformable cross-linked
      liquid-crystal polymers (CLCPs), the PtTPBP&BDPPA system was incorporated into a
      rubbery polyurethane film and then assembled with an azotolane-containing CLCP
      film. The generating assembly film bent toward the light source when irradiated
      with a 635 nm laser at low power density of 200 mW cm(-2) because the TTA-UCL was
      effectively utilized by the azotolane moieties in the CLCP film, inducing their
      trans-cis photoisomerization and an alignment change of the mesogens via an
      emission-reabsorption process. It is the first example of a soft actuator in
      which the TTA-UCL is trapped and utilized to create photomechanical effect. Such
      advantages of using this novel red-light-controllable soft actuator in potential
      biological applications have also been demonstrated as negligible thermal effect
      and its excellent penetration ability into tissues. This work not only provides a
      novel photomanipulated soft actuation material system based on the TTA-UCL
      technology but also introduces a new technological application of the TTA-based
      upconversion system in photonic devices. 

PMID- 24088068
TI  - Palladium-catalyzed fluorocarbonylation using N-formylsaccharin as CO source:
      general access to carboxylic acid derivatives.
AB  - N-formylsaccharin, an easily accessible crystalline compound, has been employed
      as an efficient CO source in Pd-catalyzed fluorocarbonylation of aryl halides to
      afford the corresponding acyl fluorides in high yields. The reactions use a near
      stoichiometric amount of the CO source (1.2 equiv) and tolerate diverse
      functional groups. The acyl fluorides obtained could be readily transformed into
      various carboxylic acid derivatives such as carboxylic acid, esters, thioesters,
      and amides in a one-pot procedure.

PMID- 24088069
TI  - Academic performance and intelligence scores of primary school-aged children with
      sickle cell anemia.
AB  - Children with sickle cell anemia (SCA) are faced with complications which may
      interfere with their educational activities including academic performance.
      Reports on their academic performance are mainly from developed countries and the
      results have been inconsistent. This study aimed to determine the academic
      performance of primary school-aged children with SCA in Nigeria and compare
      findings with a group of controls. Ninety children with SCA aged 5-11 years were
      consecutively recruited at the SCA clinic of UNTH Enugu and their age- and sex
      matched normal classmates were enrolled as controls. Academic performance of the
      children with SCA was studied using the overall scores achieved in the three term
      examinations in the preceding academic year (2009/2010), while their intelligence
      quotient (IQ) was determined using the Draw-A-Person Test. The findings were
      compared with that of 90 controls. The mean overall academic score of the
      children with SCA of 62.71 +/- 19.43% was similar to 67.47 +/- 16.42% in the
      controls (P = .077). However, a significantly higher number of children with SCA
      (32.2% vs. 16.7% of the controls; P = .015) scored below 50%, thus, had poor
      performance. The mean IQ of the subjects (91.41 +/-16.61%) was similar to that of
      the controls (95.56 +/-17.31%, P = .103). However, more SCA patients had lower IQ
      scores than controls though not statistically significant (P = 0.083). The
      overall academic performance of children with SCA, therefore, compares favorably
      with that of controls although there is a higher prevalence of poor performance
      among them. 

PMID- 24088070
TI  - Raman hyperspectral imaging of microfossils: potential pitfalls.
AB  - Initially, Raman spectroscopy was a specialized technique used by vibrational
      spectroscopists; however, due to rapid advancements in instrumentation and
      imaging techniques over the last few decades, Raman spectrometers are widely
      available at many institutions, allowing Raman spectroscopy to become a
      widespread analytical tool in mineralogy and other geological sciences.
      Hyperspectral imaging, in particular, has become popular due to the fact that
      Raman spectroscopy can quickly delineate crystallographic and compositional
      differences in 2-D and 3-D at the micron scale. Although this rapid growth of
      applications to the Earth sciences has provided great insight across the
      geological sciences, the ease of application as the instruments become
      increasingly automated combined with nonspecialists using this techique has
      resulted in the propagation of errors and misunderstandings throughout the field.
      For example, the literature now includes misassigned vibration modes,
      inappropriate spectral processing techniques, confocal depth of laser penetration
      incorrectly estimated into opaque crystalline solids, and a misconstrued
      understanding of the anisotropic nature of sp2 carbons.

PMID- 24088071
TI  - Translating immune cell cross-talk into a treatment opportunity for visceral
      leishmaniasis.

PMID- 24088073
TI  - Conference Scene: novelties in immunotherapy.
AB  - The only method aiming to permanently cure allergic disorders is allergen
      immunotherapy. Over the last 20 years there has been great progress in
      understanding the mechanisms that govern allergen immunotherapy in order to meet
      three basic prerequisites: safety, effectiveness and compliance. In the present
      summary report from the European Academy of Allergology and Clinical Immunology
      World Allergy Organization Congress held last June in Milan, we review key points
      concerning the main axes as diagnosis, novel modalities, routes and protocols, as
      well as two important immunotherapy fields: food and insect venom allergy.

PMID- 24088074
TI  - Vaccination with dendritic cell-tumor fusion cells in multiple myeloma patients:
      a promising strategy?
AB  - Evaluation of: Rosenblatt J, Avivi I, Vasir B et al. Vaccination with dendritic
      cell/tumor fusions following autologous stem cell transplant induces immunologic
      and clinical responses in multiple myeloma patients. Clin. Cancer Res. 19(13),
      3640-3648 (2013). Recently, dendritic cell (DC)-tumor fusion vaccines have been
      explored as a promising therapeutic approach for the treatment of cancer. Fusion
      vaccines offer several advantages that distinguish them from other DC-based
      vaccines. In this Phase II clinical trial, Rosenblatt et al. demonstrate that
      repeated immunization with a DC-tumor fusion vaccine after autologous stem cell
      transplantation induces myeloma-specific immunity and improves clinical response.
      They showed that generation of an autologous fusion vaccine with dendritic and
      myeloma cells was feasible and that vaccination was well tolerated without grade
      3-4 toxicities. The results of this study suggest that the time after autologous
      stem cell transplantation represents a unique setting for cancer vaccination and
      that combining autologous stem cell transplantation with post-transplant
      vaccination increases the immunogenicity. 

PMID- 24088075
TI  - Randomized, placebo-controlled Phase II trial of heat-killed Mycobacterium vaccae
      (Immodulon batch) formulated as an oral pill (V7).
AB  - AIM: A 1-month Phase II trial was conducted in 41 patients with pulmonary TB who
      were randomized into treatment (n = 20) and placebo (n = 21) arms to investigate
      the safety and efficacy of an orally-administered therapeutic TB vaccine (V7)
      containing 10 ug heat-killed Mycobacterium vaccae provided by Immodulon
      Therapeutics Ltd (London, UK). MATERIALS & METHODS: Both arms received
      conventional anti-TB therapy administered along with a daily pill of V7 or
      placebo. The subject population had four categories of TB: drug-sensitive TB;
      retreated TB; drug-resistant TB; and TB with HIV distributed in V7 and placebo
      arms at 9:4:7:6 and 14:1:6:8 ratios, respectively. RESULTS: The mycobacterial
      clearance in sputum smears was observed in 72.2% (p < 0.0001) and 19% (p = 0.03)
      of patients on V7 and placebo, respectively. The average weight accrual among V7
      recipients was 2.6 kg (p = 0.002) versus -0.2 kg (p = 0.69) in the control group.
      Except reduction in fever and increased lymphocyte counts, the changes in other
      secondary end points, such as hemoglobin, erythrocyte sedimentation rate and
      leukocyte counts, were not statistically different, although the proportion of
      patients responding favorably to V7 was invariably higher compared with placebo
      (p = 0.002). In control patients, no difference from baseline levels was noted
      except decreased hemoglobin content (p = 0.02). CONCLUSION: Oral M. vaccae was
      safe and has potential as an adjunct immunotherapy, targeting mucosal immunity,
      to improve efficacy and shorten treatment duration of TB chemotherapy.

PMID- 24088076
TI  - Prospects of apoptotic cell-based therapies for transplantation and inflammatory
      diseases.
AB  - Apoptotic cell removal or interactions of early-stage apoptotic cells with immune
      cells are associated with an immunomodulatory microenvironment that can be
      harnessed to exert therapeutic effects. While the involved immune mechanisms are
      still being deciphered, apoptotic cell infusion has been tested in different
      experimental models where inflammation is deregulated. This includes chronic and
      acute inflammatory disorders such as arthritis, contact hypersensitivity and
      acute myocardial infarction. Apoptotic cell infusion has also been used in
      transplantation settings to prevent or treat acute and chronic rejection, as well
      as to limit acute graft-versus-host disease associated with allogeneic
      hematopoietic cell transplantation. Here, we review the mechanisms involved in
      apoptotic cell-induced immunomodulation and data obtained in preclinical models
      of transplantation and inflammatory diseases. 

PMID- 24088064
TI  - The Mediator complex and transcription regulation.
AB  - The Mediator complex is a multi-subunit assembly that appears to be required for
      regulating expression of most RNA polymerase II (pol II) transcripts, which
      include protein-coding and most non-coding RNA genes. Mediator and pol II
      function within the pre-initiation complex (PIC), which consists of Mediator, pol
      II, TFIIA, TFIIB, TFIID, TFIIE, TFIIF and TFIIH and is approximately 4.0 MDa in
      size. Mediator serves as a central scaffold within the PIC and helps regulate pol
      II activity in ways that remain poorly understood. Mediator is also generally
      targeted by sequence-specific, DNA-binding transcription factors (TFs) that work
      to control gene expression programs in response to developmental or environmental
      cues. At a basic level, Mediator functions by relaying signals from TFs directly
      to the pol II enzyme, thereby facilitating TF-dependent regulation of gene
      expression. Thus, Mediator is essential for converting biological inputs
      (communicated by TFs) to physiological responses (via changes in gene
      expression). In this review, we summarize an expansive body of research on the
      Mediator complex, with an emphasis on yeast and mammalian complexes. We focus on
      the basics that underlie Mediator function, such as its structure and subunit
      composition, and describe its broad regulatory influence on gene expression,
      ranging from chromatin architecture to transcription initiation and elongation,
      to mRNA processing. We also describe factors that influence Mediator structure
      and activity, including TFs, non-coding RNAs and the CDK8 module.

PMID- 24088078
TI  - New approaches for the treatment of lupus nephritis in the 21st century: from the
      laboratory to the clinic.
AB  - Systemic lupus erythematosus is a complex autoimmune disorder affecting multiple
      organ systems. Glomerulonephritis leading to severe proteinuria, chronic renal
      failure and end-stage renal disease remains one of the most severe complications
      of systemic lupus erythematosus and is associated with significant morbidity and
      mortality. Conventional lupus nephritis (LN) treatment based on cyclophosphamide,
      steroids and, recently, mycophenolatemofetil has improved the outcome of the
      disease over the last 50 years, although failure to achieve remission or
      treatment resistance has been reported in 18-57% of patients. Chronic
      complications such as long-term toxicity dampen their ability to maintain disease
      remission. There is a need to develop more specific pharmacological agents for
      patients to provide choices that are equally effective, less toxic and have fewer
      complications. During the last 10 years, experimental studies based on different
      pathogenesis pathways of LN have provided an enormous amount of knowledge and
      have offered the possibility to target the disease with selective approaches. In
      this article, we summarize the new experimental strategies that have recently
      been utilized to target LN, focusing on mechanisms of action. 

PMID- 24088079
TI  - Epigenetics of melanoma: implications for immune-based therapies.
AB  - Malignant melanoma is a complex disease that arises and evolves due to a myriad
      of genetic and epigenetic events. Among these, the interaction between epigenetic
      alterations (i.e., histone modifications, DNA methylation, mRNA silencing by
      miRNAs and nucleosome repositioning) has been recently identified as playing an
      important role in melanoma development and progression by affecting key cellular
      pathways such as cell cycle regulation, DNA repair, apoptosis, invasion and
      immune recognition. Differently to genetic lesions, epigenetic changes are
      potentially pharmacologically reversible by using epigenetic drugs. Along this
      line, preclinical and clinical findings indicate that these drugs, given alone or
      in combination therapies, can efficiently modulate the immunophenotype of
      melanoma cells. The aim of this review is to provide a comprehensive summary of
      melanoma epigenetics and the current use of epigenetic drugs in the clinical
      setting. 

PMID- 24088077
TI  - Targeting tumor-infiltrating macrophages to combat cancer.
AB  - Tumor-associated macrophages are one of the major constituents of tumor stroma in
      many solid tumors and there is compelling preclinical and clinical evidence that
      macrophages promote cancer initiation and malignant progression. Therefore, these
      cells represent potential targets for therapeutic benefit. In this review, we
      will summarize macrophage phenotypic heterogeneity, the current understanding of
      how tumors take advantage of macrophage plasticity to generate immunosuppression,
      and how manipulation of specific macrophage populations can be used for
      therapeutic purposes through translational approaches. 

PMID- 24088080
TI  - Immunotherapy for pulmonary TB: antimicrobial peptides and their inducers.
AB  - TB is an infectious disease that still has an enormous impact on public health
      worldwide. With the continuous increasing epidemic of multidrug-resistant TB, new
      drugs and vaccines are urgently needed. In the last decade there has been a broad
      advance in the knowledge of innate immunity in TB. Together with the growing
      research regarding immunomodulators, new promising insights have been developed
      that can contribute in the control of TB. This is the case of antimicrobial
      peptides, which can be potential therapeutic or adjuvant agents. The current high
      cost of antimicrobial peptide synthesis may be a current deterrent for treatment;
      antimicrobial peptide-inducers can be an alternative for low-cost treatment
      and/or adjuvants. 

PMID- 24088081
TI  - Reciprocal effects of Toll-like receptors and miRNAs on biological processes in
      human health and disease: a systematic review.
AB  - The roles of miRNAs in human diseases are emerging. Manipulation of miRNA
      expression seems to be an effective approach to control disease severity. It has
      recently been found that Toll-like receptors and miRNAs work by exerting
      reciprocal effects. Toll-like receptor stimulation can lead to up-/down
      regulation of various miRNA expressions. Lipopolysaccharide induction may result
      in interactions between different miRNAs. Several miRNAs are involved in cancers,
      indicating the importance of identifying strategies to properly manipulate their
      expression level. The control of various miRNA expression levels, taking into
      consideration the plethora of their target genes and the possibility that this
      may lead to contracting function, which is an important issue in treatment of any
      miRNA-based (phenotype) disease. 

PMID- 24088083
TI  - An in vivo method for measuring the adsorption of plasma proteins to titanium in
      humans.
AB  - A novel method of collecting in vivo plasma proteins of humans from osteotomies
      prepared during insertion of an oral implant is described. A rod containing a
      collecting portion with a predetermined surface is introduced into the osteomy,
      removed, and transferred for enzyme-linked immunosorbent assay analysis. Two
      experiments were used to examine the feasibility of the method. In the first,
      titanium (Ti) rods with different roughness were exposed for 10 min to the blood.
      Blasted and acid-etched surfaces adsorbed four times more and acid-etched
      surfaces adosorbed two times more plasma proteins as compared to machined
      surfaces. In the second experiment, blasted and acid-etched rods were wetted for
      10 s prior to the insertion. The adsorption for fibronectin, albumin, fibrinogen,
      and IgG was enhanced significantly compared with nonwetted rods. These results
      are discussed in the light of previous methods used in studies on adsorption.
      Thus, use of the collecting instrument enables aspects of human plasma-implant
      interface to be studied in a more realistic manner. 

PMID- 24088084
TI  - An experimental and theoretical investigation of the inversion of pd@pt
      core@shell dendrimer-encapsulated nanoparticles.
AB  - Bimetallic PdPt dendrimer-encapsulated nanoparticles (DENs) having sizes of about
      2 nm were synthesized by a homogeneous route that involved (1) formation of a Pd
      core, (2) deposition of a Cu shell onto the Pd core in the presence of H2 gas,
      and (3) galvanic exchange of Pt for the Cu shell. Under these conditions, a Pd@Pt
      core@shell DEN is anticipated, but detailed characterization by in-situ extended
      X-ray absorption fine structure (EXAFS) spectroscopy and other analytical methods
      indicate that the metals invert to yield a Pt-rich core with primarily Pd in the
      shell. The experimental findings correlate well with density functional
      theoretical (DFT) calculations. Theory suggests that the increased disorder
      associated with <~2 nm diameter nanoparticles, along with the relatively large
      number of edge and corner sites, drives the structural rearrangement. This type
      of rearrangement is not observed on larger nanoparticles or in bulk metals.

PMID- 24088085
TI  - Motor speech treatment protocol for developmental motor speech disorders.
AB  - OBJECTIVE: This study examines the effect of the Motor Speech Treatment Protocol
      (MSTP), a multi-sensory hybrid treatment approach on five children (mean: 3;3
      years; S.D. 0;1) with severe to profound speech sound disorders with motor speech
      difficulties. METHODS: A multiple probe design, replicated over five
      participants, was used to evaluate the effects of treatment on improving
      listeners' auditory and visual judgements of speech accuracy. RESULTS: All
      participants demonstrated significant change between baseline and maintenance
      conditions, with the exception of KM, who may have had underlying psychosocial,
      regulation and/or attention difficulties. The training- (practiced in treatment)
      and test-words (not practiced in treatment) both demonstrated positive change in
      all participants, indicating generalization of target features to untrained
      words. CONCLUSION: These results provide preliminary evidence that the MSTP,
      which integrates multi-sensory information and utilizes hierarchical goal
      selection, may positively impact speech sound production by improving speech
      motor control in this population.

PMID- 24088086
TI  - Partially disordered proteins studied by ion mobility-mass spectrometry:
      implications for the preservation of solution phase structure in the gas phase.
AB  - The coupling of electrospray ionization (ESI) with ion mobility-mass spectrometry
      (IM-MS) allows structural studies on biological macromolecules in a solvent-free
      environment. Collision cross sections (CCSs) measured by IM-MS provide a measure
      of analyte size. For native proteins and their complexes, many structural
      features can be preserved in the gas phase, making IM-MS a powerful approach for
      a range of bioanalytical applications. In addition to tightly folded conformers,
      a large number of partially disordered proteins participate in biological
      processes and disease mechanisms. It remains unclear to what extent IM-MS is
      suitable for exploring structural properties of these semifolded species. The
      current work addresses this question, using myoglobin as model system. This
      protein follows a sequential unfolding pathway that comprises two partially
      disordered states, i.e., apo-myoglobin (aMb) at pH 7 and pH 4. IM-MS data
      acquired for these two conformers were compared to those of native holo-myoglobin
      (hMb) at pH 7 and extensively unfolded aMb at pH 2. When examining individual aMb
      charge states, the degree of gas phase unfolding is not strongly correlated with
      the corresponding solution behavior. A key problem is that non-native conformers
      generate high ESI charge states, resulting in conformational transitions caused
      by intramolecular electrostatic repulsion. It is possible to establish a link
      between solution phase and gas phase structure when normalizing CCS distributions
      according to their respective ESI-MS signal intensities. This approach yields CCS
      averages that follow the expected progression hMbpH 7 < aMbpH 7 < aMbpH 4 < aMbpH
      2. However, this trend mainly reflects the protonation behavior of the conformers
      during the ESI process, rather than a genuine memory of solution structure.
      Overall, our data reveal that electrostatically driven expansion as well as
      collapse events can lead to disparities between gaseous and solution structures
      for partially unfolded proteins. IM-MS data on non-native conformers should
      therefore be interpreted with caution. 

PMID- 24088087
TI  - Preparation and in vitro photodynamic activities of folate-conjugated distyryl
      boron dipyrromethene based photosensitizers.
AB  - Two folate-conjugated diiododistyryl boron dipyrromethenes have been prepared and
      characterized with various spectroscopic methods. These conjugates exhibit higher
      photocytotoxicity toward the KB human nasopharyngeal carcinoma cells, which have
      high expression of folate receptors when compared with the MCF-7 human breast
      adenocarcinoma cells, which have low expression of folate receptors. The
      difference in photocytotoxicity for these two cell lines is particularly large
      for the conjugate with a shorter oligoethylene glycol linker (compound 11a) as a
      result of its higher cellular uptake and slightly lower aggregation tendency. Its
      IC50 value toward KB cells (0.06 MUM) is 43-fold lower than that for MCF-7 cells,
      while the difference is only 6-fold for the analogue with a longer linker
      (compound 11b). The length of the spacer also affects their subcellular
      localization. While compound 11a shows high affinity toward the endoplasmic
      reticulum of KB cells, conjugate 11b is mainly localized in the lysosomes. 

PMID- 24088088
TI  - The dead-donor rule and the future of organ donation.

PMID- 24088089
TI  - Life or death for the dead-donor rule?

PMID- 24088090
TI  - What would you do if it were your kid?

PMID- 24088093
TI  - Noncommunicable diseases.

PMID- 24088094
TI  - Uterine fibroids.

PMID- 24088092
TI  - Long-term cognitive impairment after critical illness.
AB  - BACKGROUND: Survivors of critical illness often have a prolonged and disabling
      form of cognitive impairment that remains inadequately characterized. METHODS: We
      enrolled adults with respiratory failure or shock in the medical or surgical
      intensive care unit (ICU), evaluated them for in-hospital delirium, and assessed
      global cognition and executive function 3 and 12 months after discharge with the
      use of the Repeatable Battery for the Assessment of Neuropsychological Status
      (population age-adjusted mean [+/-SD] score, 100+/-15, with lower values
      indicating worse global cognition) and the Trail Making Test, Part B (population
      age-, sex-, and education-adjusted mean score, 50+/-10, with lower scores
      indicating worse executive function). Associations of the duration of delirium
      and the use of sedative or analgesic agents with the outcomes were assessed with
      the use of linear regression, with adjustment for potential confounders. RESULTS:
      Of the 821 patients enrolled, 6% had cognitive impairment at baseline, and
      delirium developed in 74% during the hospital stay. At 3 months, 40% of the
      patients had global cognition scores that were 1.5 SD below the population means
      (similar to scores for patients with moderate traumatic brain injury), and 26%
      had scores 2 SD below the population means (similar to scores for patients with
      mild Alzheimer's disease). Deficits occurred in both older and younger patients
      and persisted, with 34% and 24% of all patients with assessments at 12 months
      that were similar to scores for patients with moderate traumatic brain injury and
      scores for patients with mild Alzheimer's disease, respectively. A longer
      duration of delirium was independently associated with worse global cognition at
      3 and 12 months (P=0.001 and P=0.04, respectively) and worse executive function
      at 3 and 12 months (P=0.004 and P=0.007, respectively). Use of sedative or
      analgesic medications was not consistently associated with cognitive impairment
      at 3 and 12 months. CONCLUSIONS: Patients in medical and surgical ICUs are at
      high risk for long-term cognitive impairment. A longer duration of delirium in
      the hospital was associated with worse global cognition and executive function
      scores at 3 and 12 months. (Funded by the National Institutes of Health and
      others; BRAIN-ICU ClinicalTrials.gov number, NCT00392795.).

PMID- 24088095
TI  - Images in clinical medicine. Porphyria cutanea tarda and hypertrichosis.

PMID- 24088096
TI  - Clinical problem-solving. Venting the spleen.

PMID- 24088097
TI  - Delivering twins.

PMID- 24088098
TI  - Disability after critical illness.

PMID- 24088099
TI  - Clinical decisions. Glycemic management in a patient with type 2 diabetes.

PMID- 24088091
TI  - A randomized trial of planned cesarean or vaginal delivery for twin pregnancy.
AB  - BACKGROUND: Twin birth is associated with a higher risk of adverse perinatal
      outcomes than singleton birth. It is unclear whether planned cesarean section
      results in a lower risk of adverse outcomes than planned vaginal delivery in twin
      pregnancy. METHODS: We randomly assigned women between 32 weeks 0 days and 38
      weeks 6 days of gestation with twin pregnancy and with the first twin in the
      cephalic presentation to planned cesarean section or planned vaginal delivery
      with cesarean only if indicated. Elective delivery was planned between 37 weeks 5
      days and 38 weeks 6 days of gestation. The primary outcome was a composite of
      fetal or neonatal death or serious neonatal morbidity, with the fetus or infant
      as the unit of analysis for the statistical comparison. RESULTS: A total of 1398
      women (2795 fetuses) were randomly assigned to planned cesarean delivery and 1406
      women (2812 fetuses) to planned vaginal delivery. The rate of cesarean delivery
      was 90.7% in the planned-cesarean-delivery group and 43.8% in the planned-vaginal
      delivery group. Women in the planned-cesarean-delivery group delivered earlier
      than did those in the planned-vaginal-delivery group (mean number of days from
      randomization to delivery, 12.4 vs. 13.3; P=0.04). There was no significant
      difference in the composite primary outcome between the planned-cesarean-delivery
      group and the planned-vaginal-delivery group (2.2% and 1.9%, respectively; odds
      ratio with planned cesarean delivery, 1.16; 95% confidence interval, 0.77 to
      1.74; P=0.49). CONCLUSIONS: In twin pregnancy between 32 weeks 0 days and 38
      weeks 6 days of gestation, with the first twin in the cephalic presentation,
      planned cesarean delivery did not significantly decrease or increase the risk of
      fetal or neonatal death or serious neonatal morbidity, as compared with planned
      vaginal delivery. (Funded by the Canadian Institutes of Health Research;
      ClinicalTrials.gov number, NCT00187369; Current Controlled Trials number,
      ISRCTN74420086.).

PMID- 24088100
TI  - Suppressing the antibody response with Siglec ligands.

PMID- 24088101
TI  - Clopidogrel with aspirin in minor stroke or transient ischemic attack.

PMID- 24088102
TI  - Clopidogrel with aspirin in minor stroke or transient ischemic attack.

PMID- 24088103
TI  - Clopidogrel with aspirin in minor stroke or transient ischemic attack.

PMID- 24088104
TI  - Clopidogrel with aspirin in minor stroke or transient ischemic attack.

PMID- 24088105
TI  - Eculizumab in atypical hemolytic-uremic syndrome.

PMID- 24088106
TI  - Eculizumab in atypical hemolytic-uremic syndrome.

PMID- 24088107
TI  - Eculizumab in atypical hemolytic-uremic syndrome.

PMID- 24088108
TI  - Eculizumab in atypical hemolytic-uremic syndrome.

PMID- 24088109
TI  - Eculizumab in atypical hemolytic-uremic syndrome.

PMID- 24088110
TI  - Mental health and the global agenda.

PMID- 24088111
TI  - Mental health and the global agenda.

PMID- 24088112
TI  - Mental health and the global agenda.

PMID- 24088113
TI  - Primaquine failure and cytochrome P-450 2D6 in Plasmodium vivax malaria.

PMID- 24088114
TI  - Images in clinical medicine. Peristaltic waves in pyloric stenosis.

PMID- 24088115
TI  - Formation and base hydrolysis of oxidimethaneamine bridges in CoIII-amine
      complexes.
AB  - cis-[CoL2](3+) (1a(3+)), trans-[CoL2](3+) (2a(3+)), cis-[Co(MeL)2](3+) (1b(3+)),
      and trans-[Co(MeL)2](3+) (2b(3+)), L = 1,4-diazepan-6-amine (daza) and MeL = 6
      methyl-1,4-diazepan-6-amine (Medaza), were allowed to react as templates in
      acetonitrile with paraformaldehyde and triethylamine. Several Co(III) complexes,
      where two adjacent amino groups of two ligand moieties are interlinked by an
      oxidimethaneamine bridge, were obtained. Connection of a primary with a secondary
      amino group (prim-sec bridging) was found to be predominant. The singly and
      doubly bridged daza- and Medaza-derivatives 7a(3+), 9a(3+) and 7b(3+), 9b(3+)
      were characterized by crystal-structure analysis. The bridging process resulted
      in a slight lengthening of the mean Co-N distance, a red shift of the A1g-T1g
      transition, and an increase of the Co(III)/Co(II) reduction potential. Several
      minor components, which could be only partially separated by chromatographic
      methods, were also formed. The daza-derivatives 6a(3+) (prim-prim bridged) and
      10a(3+) (bidentate coordination of one daza frame) formed in small quantities.
      The Medaza derivatives 3b(3+) and 4b(3+) (trans configuration of the Medaza
      frames, with additional pending carbinolamino groups), and 8b(3+) (with a
      methylideneimino group) represent intermediates of the condensation process.
      Their structure was again corroborated by X-ray diffraction. All bridged species
      (6a(3+), 7a(3+), 7b(3+), 8b(3+), 9a(3+), 9b(3+), and 10a(3+)) exhibited
      exclusively a cis orientation of the two diazepane frames, even if the trans
      configured 2a(3+) or 2b(3+) were used as starting materials. Molecular mechanics
      calculations indicate that in the bridged species with a trans configuration
      steric strain is substantially more pronounced. In alkaline aqueous media, 9a(3+)
      and 9b(3+) revealed a complete degradation of the bridges whereby the original
      1a(3+) and 1b(3+) reformed. The pseudo-first-order rate constant k(obs) of the
      degradation reaction was found to depend linearly on OH(-) concentration. The
      degradation of the first bridge is about 100 times faster than the degradation of
      the second. The mechanism of formation and degradation of such oxidimethaneamine
      bridges is discussed. 

PMID- 24088118
TI  - Comparisons of apparent mass responses of human subjects seated on rigid and
      elastic seats under vertical vibration.
AB  - The apparent mass (AM) responses of human body seated on elastic seat, without
      and with a vertical back support, are measured using a seat pressure sensing mat
      under three levels of vertical vibration (0.25, 0.50 and 0.75 m/s(2) rms
      acceleration) in 0.50-20 Hz frequency range. The responses were also measured
      with a rigid seat using the pressure mat and a force plate in order to examine
      the validity of the pressure mat. The pressure mat resulted in considerably lower
      AM magnitudes compared to the force plate. A correction function was proposed and
      applied, which resulted in comparable AM from both measurement systems for the
      rigid seat. The correction function was subsequently applied to derive AM of
      subjects seated on elastic seat. The responses revealed lower peak magnitude and
      corresponding frequency compared to those measured with rigid seat, irrespective
      of back support and excitation considered.

PMID- 24088119
TI  - Lower lip pits: van der woude or kabuki syndrome?
AB  - Kabuki syndrome (KS) is a multiple congenital anomaly/mental retardation syndrome
      with characteristic facial features. Despite more than 350 documented cases and
      recent correlation of MLL2 mutations as a genetic cause, its full clinical
      spectrum is still being defined. This report describes two patients who were
      initially diagnosed with Van der Woude syndrome (VWS) based on the presence of
      lower lip pits. However, this finding can occur with KS, albeit infrequently. For
      patients with lower lip pits, a thorough evaluation should be made to distinguish
      between VWS and KS, as there are differences in long-term prognosis. 

PMID- 24088120
TI  - Can occlusal evaluation of children with unilateral cleft lip and palate help
      determine future maxillofacial morphology?
AB  - Objective : To investigate the change in occlusal evaluations from the 5-year
      olds' index to the Goslon Yardstick and to compare the relationship between the
      evaluations and maxillofacial growth in patients with complete unilateral cleft
      lip and palate (UCLP). Design : A prospective longitudinal study. Subjects : The
      sample consisted of 85 patients with complete UCLP who underwent surgery from
      1969 to 1994 and were treated at the Kyushu University Hospital in Fukuoka,
      Japan. Subjects had two serial dental casts performed at the ages of 5 and 10
      years. Furthermore, each patient had lateral cephalographs taken at the age of 5
      years, 76 of 85 subjects had films taken at the age of 10 years, and 54 subjects
      also had lateral cephalograms taken after the age of 15 years. Methods : Every
      dental cast was evaluated by the 5-year-olds' index and the Goslon Yardstick,
      respectively. The lateral cephalographs were traced and digitized, and angular
      dimensions were calculated. Outcomes were compared using Spearman's rank-order
      correlation analysis and the Kruskal-Wallis analysis. Results and Conclusion :
      Dental arch relationships were evaluated and rated as 2.96 in the 5-year-olds'
      index and 2.85 in the Goslon Yardstick, respectively. Both groupings showed a
      significant relationship, and they showed no change in 36 out of 85 subjects
      (42.3%), significant improvement in 30 (35.3%), and deterioration in 19 (22.3%).
      Two occlusal groupings and maxillofacial morphology on the cephalographs
      indicated that the grouping reflected the anteroposterior position of the
      mandible. Moreover, both groupings showed some relation to previous maxillofacial
      growth, but they did not show any relationship with future growth. The Goslon
      Yardstick may not predict maxillofacial morphology in adulthood. 

PMID- 24088121
TI  - Making data on essential pharmacogenes available for every patient everywhere:
      the Medicine Safety Code initiative.

PMID- 24088122
TI  - Sunny outlook for personalized medicine: tamoxifen and beyond.

PMID- 24088123
TI  - Transporter pharmacogenetics: do we need function? Do we need motion?

PMID- 24088125
TI  - beta1- and alpha2C-adrenergic receptor polymorphisms and the antiarrhythmic
      effect of bucindolol in heart failure with reduced ejection fraction.

PMID- 24088126
TI  - Relationship between CYP2D6 genotype and haloperidol pharmacokinetics and
      extrapyramidal symptoms in healthy volunteers.
AB  - AIM: This study aimed to elucidate the relationship between CYP2D6 genotype and
      haloperidol pharmacokinetics and induced extrapyramidal symptoms (EPSs).
      MATERIALS & METHODS: Twenty five healthy subjects were included in this
      randomized, placebo-controlled, single-dose (5 mg) crossover and double-blind
      clinical trial, selected according to their CYP2D6 genotype and classified as
      poor metabolizers (n = 8), extensive metabolizers (n = 10) and ultrarapid
      metabolizers (n = 7). RESULTS & CONCLUSION: We confirm that CYP2D6 genotype
      partially determines haloperidol metabolism and the rate of EPSs measured as
      wakefulness activity by actigraphy. The best predictor of wakefulness activity
      was the model including haloperidol area under the plasma concentration-time
      curve, sex and tranquilization, which explained 48.3% of the total variance.
      However, other markers need to be identified in order to explain the observed
      variability of haloperidol response and to develop pharmacogenetic predictors of
      haloperidol-induced EPSs.

PMID- 24088127
TI  - Pharmacogenetics of antiplatelets and anticoagulants: a report on clopidogrel,
      warfarin and dabigatran.
AB  - Genetic polymorphisms are thought to contribute to the wide intraindividual
      variability in antiplatelet and anticoagulant drug response. Pharmacogenetics is
      the study of how genetic variants influence drug response and how the adoption of
      a more personalized approach in antiplatelet and anticoagulant therapy may help
      to minimize harmful drug effects and optimize care for individual patients.
      However, due to sometimes conflicting evidence, the uptake of pharmacogenetics in
      the clinical setting has been slow. In this article, we review the genetic
      mechanisms contributing to the variability in response to three commonly used and
      emerging antiplatelet and anticoagulant drug therapies, namely clopidogrel,
      warfarin and dabigatran. We will focus on common genetic variants that influence
      the absorption, metabolism and/or action of these agents, including CYP2C19 (*2,
      *3 and *17), CYP3A4, CYP3A5, CYP2C9, ABCB1, P2RY12, CYP2C9 (*2/*3), VKORC1 and
      CESI. 

PMID- 24088128
TI  - Polymorphisms in the organic anion transporting polypeptide genes influence liver
      parenchymal enhancement in gadoxetic acid-enhanced MRI.
AB  - AIM: This study aimed to investigate whether genetic polymorphisms of the organic
      anion transporting polypeptides influence hepatic enhancement in gadoxetic acid
      enhanced MRI. PATIENTS & METHODS: We analyzed the genotypes of SLCO1B1 388A>G,
      SLCO1B1 521T>C, SLCO1B3 334T>G and NR1H4 -1G>T and calculated the mean
      quantitative liver-spleen contrast ratio, as an index of liver parenchymal
      enhancement, in 226 patients with liver disease. RESULTS: Multiple linear
      regression analysis using the mean quantitative liver-spleen contrast ratio as
      the dependent variable revealed that not only Child-Pugh score, but also
      SLCO1B1*1b haplotype (beta = 0.12; p = 0.04), were significant predictors of
      liver parenchymal enhancement. In addition, SLCO1B3 334T>G (beta = -0.18; p =
      0.03) was a significant predictor when the data were analyzed in a subgroup of
      117 patients, excluding the carriers of NR1H4 -1G>T, who reportedly exhibit
      reduced transcriptional activity of SLCO1B3. CONCLUSION: These genetic variants,
      as well as hepatic function, may contribute to individual differences in hepatic
      enhancement with gadoxetic acid.

PMID- 24088129
TI  - Comparative study of polymorphism frequencies of the CYP2D6, CYP3A5, CYP2C8 and
      IL-10 genes in Mexican and Spanish women with breast cancer.
AB  - AIM: Pharmacogenetic studies in breast cancer (BC) may predict the efficacy of
      tamoxifen and the toxicity of paclitaxel and capecitabine. We determined the
      frequency of polymorphisms in the CYP2D6 gene associated with activation of
      tamoxifen, and those of the genes CYP2C8, CYP3A5 and DPYD associated with
      toxicity of paclitaxel and capecitabine. We also included a IL-10 gene
      polymorphism associated with advanced tumor stage at diagnosis. PATIENTS &
      METHODS: Genomic DNAs from 241 BC patients from northeast Mexico were genotyped
      using DNA microarray technology. RESULTS: For tamoxifen processing, CYP2D6
      genotyping predicted that 90.8% of patients were normal metabolizers, 4.2%
      ultrarapid, 2.1% intermediate and 2.9% poor metabolizers. For paclitaxel and the
      CYP2C8 gene, 75.3% were normal, 23.4% intermediate and 1.3% poor metabolizers.
      Regarding the DPYD gene, only one patient was a poor metabolizer. For the IL-10
      gene, 47.1% were poor metabolizers. CONCLUSION: These results contribute valuable
      information towards personalizing BC chemotherapy in Mexican women.

PMID- 24088130
TI  - Impact of genotype-guided dosing on anticoagulation visits for adults starting
      warfarin: a randomized controlled trial.
AB  - AIM: This study aimed to assess the effectiveness of genotype-guided warfarin
      dosing. PATIENTS & METHODS: A total of 109 adults were randomized to receive
      initial dosing as determined by an algorithm containing genetic (VKORC1 and
      CYP2C9) plus clinical information or only clinical information. Primary end
      points were the number of anticoagulation visits and the time in therapeutic
      range (TTR) over 90 days. Secondary end points included time to therapeutic dose,
      International Normalized Ratios of >4, emergency visits, hospitalizations,
      hemorrhagic events, thrombotic events and mortality. RESULTS: Neither primary end
      point was significantly different between groups (anticoagulation visits: 6.96 vs
      6.37, p = 0.51; TTR: 0.40 vs 0.43, p = 0.59). Fewer emergency visits,
      hospitalizations, major hemorrhagic events, thrombotic events and deaths occurred
      in the genetic plus clinical group than in the clinical only group, but these
      differences were not statistically significant. CONCLUSION: Genotype-guided
      dosing did not decrease the number of anticoagulation visits or improve TTR. Our
      trial was not powered to detect anything but large differences for utilization
      and health outcomes.

PMID- 24088131
TI  - Long-term effects of ABCB1 and SXR SNPs on the systemic exposure to cyclosporine
      in pediatric kidney transplant patients.
AB  - AIM: Cyclosporine is characterized by a wide interindividual variability in its
      pharmacokinetics. The objective of this study was to evaluate the effects of
      ABCB1 and SXR SNPs on cyclosporine exposure in a group of kidney transplant
      patients followed up from childhood to adulthood. PATIENTS & METHODS: Recipients
      were genotyped for ABCB1 C1236T, G2677T/A and C3435T, and for SXR RS3842689 and
      A7635G. Dose-adjusted trough levels and weight-adjusted daily doses were compared
      among patients according to allelic status by a generalized estimation equation
      approach that allows longitudinal data analyses. RESULTS: A genotype-dependent
      effect was found in all ABCB1 genotypes and in one of the SXR SNPs. This effect
      was particularly evident for the TT genotype of the ABCB1 G2677T/A SNP, the TT
      genotype of the ABCB1 C3435T SNP and for heterozygotes of the deletion of 6 bp in
      the promoter region of SXR. CONCLUSION: The presence of specific ABCB1 and SXR
      SNPs could significantly affect cyclosporine exposure during a kidney transplant
      patient's development from childhood to adulthood in a time-dependent fashion.

PMID- 24088132
TI  - CYP2W1 polymorphism: functional aspects and relation to risk for colorectal
      cancer.
AB  - AIM: This study aims to investigate the possible association between the risk of
      colorectal cancer (CRC) and allelic variants of CYP2W1 and their functional
      properties. MATERIALS & METHODS: The distribution of three different CYP2W1
      alleles (CYP2W1*1, CYP2W1*2 and CYP2W1*6) in 1785 CRC patients and 1761 healthy
      blood donors was determined using the TaqMan((r)) (Applied Biosystems, CA, USA)
      allelic discrimination assay or allele-specific amplification. Corresponding gene
      products (CYP2W1.1, CYP2W1.2 and CYP2W1.6) were expressed in human colon cancer
      SW480 cells and their activities towards two different substrates, the
      duocarmycin analogs ICT2706 and ICT2726, were monitored. RESULTS: No significant
      differences in the distribution of CYP2W1*1, CYP2W1*2 and CYP2W1*6 alleles were
      found between CRC patients and controls. The CYP2W1.1, CYP2W1.2 and CYP2W1.6
      variant enzymes were expressed at the similar levels in the transfected SW480
      cells and had comparable kinetics in terms of the metabolism of the duocarmycin
      ICT2726, as well as in the bioactivation of ICT2706 into a cytotoxic product.
      CONCLUSION: These epidemiological data obtained from a large population of CRC
      patients and controls cannot confirm the previously suggested decreased risk for
      CRC among carriers of CYP2W1*2. On the molecular level, this conclusion is
      further supported by the similar catalytic characteristics of the CYP2W1.1,
      CYP2W1.2 and CYP2W1.6 variants of CYP2W1.

PMID- 24088133
TI  - Pharmacogenetics of topical and systemic treatment of psoriasis.
AB  - Psoriasis is a chronic inflammatory skin disease. The cause of psoriasis is
      unknown, although genetics may play a key role in its development. Treatment of
      the disease varies with severity. Topical drugs, such as corticosteroids, coal
      tar, retinoids and vitamin D analogs, are commonly used to treat mild psoriasis.
      Phototherapy and systemic drugs, such as calcineurin inhibitors, methotrexate,
      acitretin and biological drugs, are usually used to treat moderate-to-severe
      psoriasis. Not all patients respond well to treatment, and some can develop
      severe adverse effects. Interindividual differences in several genes may explain
      this variation in response to treatment. Pharmacogenetics and pharmacogenomics
      can facilitate more personalized medicine and prevent the adverse effects
      associated with treatment. 

PMID- 24088134
TI  - Pharmacogenetics of neural injury recovery.
AB  - Relatively few pharmacological agents are part of routine care for neural injury,
      although several are used or under consideration in acute stroke, chronic stroke,
      traumatic brain injury and secondary stroke prevention. Tissue plasminogen
      activator is approved for the treatment of acute ischemic stroke, and genetic
      variants may impact the efficacy and safety of this drug. In the chronic phase of
      stroke, several drugs such as L-dopa, fluoxetine and donepezil are under
      investigation for enhancing rehabilitation therapy, with varying levels of
      evidence. One potential reason for the mixed efficacy displayed by these drugs
      may be the influence of genetic factors that were not considered in prior
      studies. An understanding of the genetics impacting the efficacy of dopaminergic,
      serotonergic and cholinergic drugs may allow clinicians to target these potential
      therapies to those patients most likely to benefit. In the setting of stroke
      prevention, which is directly linked to neural injury recovery, the most highly
      studied pharmacogenomic interactions pertain to clopidogrel and warfarin.
      Incorporating pharmacogenomics into neural injury recovery has the potential to
      maximize the benefit of several current and potential pharmacological therapies
      and to refine the choice of pharmacological agent that may be used to enhance
      benefits from rehabilitation therapy. 

PMID- 24088135
TI  - Impact of biomarkers on clinical trial risk.
AB  - The last decade has witnessed the cost of drug development rise dramatically;
      concurrently, the number of new drug approvals has declined. Clinical trial
      failure rates have contributed significantly to this 'innovation' crisis and are
      directly related to clinical trial risk. One strategy that is often touted to
      resolve this challenge depends on embracing a personalized medicine approach
      where treatment is tailored to a patient's unique genetic background. We
      highlight a new risk-based paradigm of clinical trial risk that evaluates the
      utility of biomarkers in drug development and their risk mitigation benefits.
      Furthermore, examples elucidating the current state of biomarker integration
      during clinical trials and the potential risks posed by doing so will be
      discussed. 

PMID- 24088136
TI  - VEGF pathway polymorphisms as prognostic and pharmacogenetic factors in cancer: a
      2013 update.
AB  - With the recent advances in genomic medicine and the development of targeted
      antiangiogenic therapy for cancer patients, there has been an increased interest
      in the role of predictive and prognostic markers for antiangiogenic therapy.
      Here, we provide a summary of the angiogenesis pathway, the role of predictive
      and prognostic markers in cancer and a summary of the current literature and
      studies on predictive and prognostic markers for antiangiogenic therapy. Our aim
      is to summarize those studies that are currently in the literature with an
      emphasis on the future directions of the field from 2013 and beyond. We conclude
      by providing our perspective on the future directions of this growing field, as
      well as possible challenges and pitfalls along the way. 

PMID- 24088138
TI  - Redox potentials and protonation of the A-cluster from acetyl-CoA synthase. A
      density functional theory study.
AB  - Density functional theory (DFT/BP86) and the polarized continuum model
      (PCM/epsilon = 20) have been applied to perform calculations for the A-cluster of
      acetyl-CoA synthase enzyme. The geometry optimization was carried out for the
      oxidized, one- and two-electron reduced A-cluster as well as for A-cluster with
      ligands important in the catalytic cycle, i.e., H2O, CO, CH3, OH(-), and H(+).
      The electronic structure of the studied species (spin densities and NBO charges)
      was analyzed and the metal-metal interactions were investigated with the use of
      Wiberg bond indices (WBIs). The pKa values and the reduction potentials have been
      determined. On the basis of the calculations, the mechanism of PCET reductive
      activation of the A-cluster has been proposed for the methylation catalytic step.

PMID- 24088140
TI  - Enhanced hydrolytic degradation of heterografted polyglycidols:
      phosphonoethylated monoester and polycaprolactone grafts.
AB  - Novel biodegradable materials with tunable hydrolytic degradation rate are
      prepared by grafting of phosphonoethylated polyglycidols with polyesters. First,
      the hydrolytically degradable polyester grafts are attached to polyglycidols
      partially grafted with phosphonoethylated diethyl esters through chemical
      catalyzed grafting using tin(II) octanoate, then the diethyl ester groups are
      chemoselectively converted to the corresponding monoester (mixed
      phosphonate/phosphonic acid) using alkali metal halides. The products are
      characterized by means of (1)H, (13)C, and (31)P NMR spectroscopy, as well as
      size-exclusion chromatography and differential scanning calorimetry. The in vitro
      degradation of the copolymers is studied in phosphate buffered solution at 55 
      degrees C. The copolymers are of the same architecture, molecular weight, and
      crystallinity, only differing in the pendant phosphonate and mixed
      phosphonate/phosphonic acid groups, respectively. On the basis of mass loss,
      decrease of the molecular weight, and morphological analysis of the copolymers,
      the strong impact of mixed phosphonate/phosphonic acid groups on the hydrolytic
      degradation rate is demonstrated. 

PMID- 24088139
TI  - Physiological and proteomic analyses of drought stress response in Holm oak
      provenances.
AB  - Responses to drought stress by water withholding have been studied in 1 year old
      Holm oak (Quercus ilex subsp. ballota [Desf.] Samp.) seedlings from seven
      provenances from Andalusia (southern Spain). Several physiological parameters,
      including predawn xylem water potentials and relative water content in soil,
      roots, and leaves as well as maximum quantum efficiency and yield of PSII were
      evaluated for 28 days in both irrigated and nonirrigated seedlings. The leaf
      proteome map of the two provenances that show the extreme responses (Seville,
      GSE, is the most susceptible, while Almeria, SSA, is the least susceptible) was
      obtained. Statistically significant variable spots among provenances and
      treatments were subjected to MALDI-TOF/TOF-MS/MS analysis for protein
      identification. In response to drought stress, ~12.4% of the reproducible spots
      varied significantly depending on the treatment and the population. These
      variable proteins were mainly chloroplastic and belonged to the metabolism and
      defense/stress functional categories. The 2-DE protein profile of nonirrigated
      seedlings was similar in both provenances. Physiological and proteomics data were
      generally in good agreement. The general trend was a decrease in protein
      abundance upon water withholding in both provenances, mainly in those involved in
      ATP synthesis and photosynthesis. This decrease, moreover, was most marked in the
      most susceptible population compared with the less susceptible one.

PMID- 24088141
TI  - Sinus implants for chronic rhinosinusitis: technology evaluation.
AB  - INTRODUCTION: Endoscopic sinus surgery (ESS) plays an integral role in the
      treatment of chronic rhinosinusitis (CRS), with well-documented benefits in both
      symptoms and quality of life. However, synechiae formation, polypoid change, and
      mucosal edema can compromise long-term surgical outcomes. Corticosteroids have
      been found to be effective in managing such postsurgical inflammation, but
      current delivery methods are limited by poor sinonasal distribution and potential
      systemic side effects. Sinus implantation offers a novel vehicle for topical drug
      delivery in CRS; enabling sustained, controlled corticosteroid application
      directly to sinonasal mucosa. AREAS COVERED: The bioengineering, mechanism of
      drug delivery, degradation and resorption of sinus implantation will be
      delineated. Research findings from animal and clinical studies will be assessed
      as well as alternative devices. Future directions for this technology in the
      management of CRS will also be discussed. EXPERT OPINION: The sinus implant is a
      revolutionary mode of localized drug delivery in CRS. Its utilization enhances
      wound healing, with diminished need for secondary postoperative medical and
      surgical interventions. Such novel technology has far-reaching implications, with
      future indications likely extending beyond the operating room into the clinic
      setting, to treat CRS patients, with inflammatory exacerbations or recurrent
      polypoid disease, who would otherwise require additional surgery.

PMID- 24088142
TI  - High-efficiency polymer solar cells via the incorporation of an amino
      functionalized conjugated metallopolymer as a cathode interlayer.
AB  - An amino-functionalized conjugated metallopolymer PFEN-Hg was developed as a
      cathode interlayer for inverted polymer solar cells. The resulting devices
      exhibited significantly improved performance with power conversion efficiencies
      exceeding 9%. Moreover, good device performance was achievable with the PFEN-Hg
      over a wider range of film thickness, likely due to the Hg-Hg interactions and
      improved pi-pi stacking. 

PMID- 24088143
TI  - Introduction: Institutional corruption and the pharmaceutical policy.
AB  - Today, the goals of pharmaceutical policy and medical practice are often
      undermined due to institutional corruption - that is, widespread or systemic
      practices, usually legal, that undermine an institution's objectives or
      integrity. In this symposium, 16 articles investigate the corruption of
      pharmaceutical policy, each taking a different look at the sources of corruption,
      how it occurs, and what is corrupted. We will see that the pharmaceutical
      industry's own purposes are often undermined. Furthermore, pharmaceutical
      industry funding of election campaigns and lobbying skews the legislative process
      that sets pharmaceutical policy. Moreover, certain practices have corrupted
      medical research, the production of medical knowledge, the practice of medicine,
      drug safety, the Food and Drug Administration's oversight of the pharmaceutical
      market, and the trustworthiness of patient advocacy organizations. 

PMID- 24088144
TI  - Foreword: "Institutional corruption" defined.

PMID- 24088145
TI  - Parallel problems: Applying institutional corruption analysis of Congress to big
      pharma.
AB  - Dennis Thompson and Lawrence Lessig are leading thinkers in the realm of
      institutional corruption, the notion that inappropriate dependencies and
      conflicts of interest undercut the ethical foundations of institutions on which
      society relies. Both are particularly known for their work on institutional
      corruption as it affects government and politics. This essay examines the
      applicability of their writing to the private sector, particularly as it relates
      to vital and influential industries like pharmaceuticals. 

PMID- 24088146
TI  - Pharmaceuticals, political money, and public policy: a theoretical and empirical
      agenda.
AB  - Why, when confronted with policy alternatives that could improve patient care,
      public health, and the economy, does Congress neglect those goals and tailor
      legislation to suit the interests of pharmaceutical corporations? In brief, for
      generations, the pharmaceutical industry has convinced legislators to define
      policy problems in ways that protect its profit margin. It reinforces this
      framework by selectively providing information and by targeting campaign
      contributions to influential legislators and allies. In this way, the industry
      displaces the public's voice in developing pharmaceutical policy. Unless citizens
      mobilize to confront the political power of pharmaceutical firms, objectionable
      industry practices and public policy will not change. Yet we need to refine this
      analysis. I propose a research agenda to uncover pharmaceutical influence. It
      develops the theory of dependence corruption to explain how the pharmaceutical
      industry is able to deflect the broader interests of the general public. It
      includes empirical studies of lobbying and campaign finance to uncover the means
      drug firms use to: (1) shape the policy framework adopted and information used to
      analyze policy; (2) subsidize the work of political allies; and (3) influence
      congressional voting. 

PMID- 24088147
TI  - Corruption of pharmaceutical markets: addressing the misalignment of financial
      incentives and public health.
AB  - This paper explains how the current architecture of the pharmaceutical markets
      has created a misalignment of financial incentives and public health that is a
      central cause of harmful practices. It explores three possible solutions to
      address that misalignment: taxes, increased financial penalties, and drug pricing
      based on value. Each proposal could help to partly realign financial incentives
      and public health. However, because of the limits of each proposal, there is no
      easy solution to fixing the problem of financial incentives. 

PMID- 24088148
TI  - Five un-easy pieces of pharmaceutical policy reform.
AB  - Improper dependencies slant policy over a drug's life span, biasing the
      development of new drugs, the testing and marketing approval for new drugs, and
      the monitoring of patient safety after drugs are marketed. This article examines
      five ways in which the public improperly depends on pharmaceutical firms that
      compromise the integrity of pharmaceutical policy. Today the public relies on
      pharmaceutical firms: (1) to set priorities on drug research and development; (2)
      to conduct clinical trials to test whether drugs are safe and effective; (3) to
      decide what clinical trial data to disclose to the public; (4) to monitor post
      marketing drug safety; (5) to supply product information to physicians and to
      finance continuing medical education and other professional activities. The
      article suggests options to overcome each of these dependencies. 

PMID- 24088149
TI  - Institutional corruption of pharmaceuticals and the myth of safe and effective
      drugs.
AB  - Over the past 35 years, patients have suffered from a largely hidden epidemic of
      side effects from drugs that usually have few offsetting benefits. The
      pharmaceutical industry has corrupted the practice of medicine through its
      influence over what drugs are developed, how they are tested, and how medical
      knowledge is created. Since 1906, heavy commercial influence has compromised
      congressional legislation to protect the public from unsafe drugs. The
      authorization of user fees in 1992 has turned drug companies into the FDA's prime
      clients, deepening the regulatory and cultural capture of the agency. Industry
      has demanded shorter average review times and, with less time to thoroughly
      review evidence, increased hospitalizations and deaths have resulted. Meeting the
      needs of the drug companies has taken priority over meeting the needs of
      patients. Unless this corruption of regulatory intent is reversed, the situation
      will continue to deteriorate. We offer practical suggestions including:
      separating the funding of clinical trials from their conduct, analysis, and
      publication; independent FDA leadership; full public funding for all FDA
      activities; measures to discourage R&D on drugs with few, if any, new clinical
      benefits; and the creation of a National Drug Safety Board. 

PMID- 24088150
TI  - From bad pharma to good pharma: aligning market forces with good and trustworthy
      practices through accreditation, certification, and rating.
AB  - This article explores whether the bioethical performance and trustworthiness of
      pharmaceutical companies can be improved by harnessing market forces through the
      use of accreditation, certification, or rating. Other industries have used such
      systems to define best practices, set standards, and assess and signal the
      quality of services, processes, and products. These systems have also informed
      decisions in other industries about where to invest, what to buy, where to work,
      and when to regulate. Similarly, accreditation, certification, and rating
      programs can help drug companies address stakeholder concerns in four areas:
      clinical trial design and management, dissemination of clinical trial results,
      marketing practices, and the accessibility of medicines. To illuminate processes 
      such as conflicts of interests and revolving-door policies - that can jeopardize
      the integrity of accreditation, certification, and ratings systems, the article
      concludes with a consideration of recent failures of credit-rating agencies and a
      review of the regulatory capture literature. 

PMID- 24088151
TI  - Understanding pharmaceutical research manipulation in the context of accounting
      manipulation.
AB  - The problem of the manipulation of data that arises when there is both
      opportunity and incentive to mislead is better accepted and studied - though by
      no means solved - in financial accounting than in medicine. This article analyzes
      pharmaceutical company manipulation of medical research as part of a broader
      problem of corporate manipulation of data in the creation of accounting profits.
      The article explores how our understanding of accounting fraud and misinformation
      helps us understand the risk of similar information manipulation in the medical
      sciences. This understanding provides a framework for considering how best to
      improve the quality of medical research and analysis in light of the current
      system of medical information production. I offer three possible responses: (1)
      use of the Dodd-Frank whistleblower provisions to encourage reporting of medical
      research fraud; (2) a two-step academic journal review process for clinical
      trials; and (3) publicly subsidized trial-failure insurance. These would improve
      the release of negative information about drugs, thereby increasing the
      reliability of positive information. 

PMID- 24088152
TI  - Curbing misconduct in the pharmaceutical industry: insights from behavioral
      ethics and the behavioral approach to law.
AB  - Two insights of psychology on which we would like to draw are that people react
      to law in more complex ways than rational-choice models assume and that good
      people sometimes do bad things. With that starting point, this article provides a
      behavioral perspective on some of the factors that policymakers seeking to reduce
      the level of misconduct in the pharmaceutical industry should consider. Effective
      regulation and enforcement need to address the following questions: Who are the
      regulation's targeted actors - researchers or executives? Are the regulations
      directed toward research or marketing activities? Is the misconduct a product of
      explicit rational choice or implicit processes of which the actor is unaware? Is
      it reasonable to address all types of misconduct using the same approach? Certain
      misconduct - particularly by researchers - is due to automatic, intuitive, and
      unconscious decisions and needs to be addressed through different means than
      those used to address misconduct due to controlled, deliberate decisions. This
      article therefore recommends using different sorts of regulation depending on the
      context. It suggests more tailored enforcement mechanisms that will be sensitive
      to the pharmaceutical researchers' unique work motivations and to their awareness
      or lack of awareness of their own misconduct. 

PMID- 24088153
TI  - The ethics of pharmaceutical research funding: a social organization approach.
AB  - This paper advances a social organization approach to examining unethical
      behavior. While unethical behaviors may stem in part from failures in individual
      morality or psychological blind spots, they are both generated and performed
      through social interactions among individuals and groups. To illustrate the value
      of a social organization approach, a case study of a medical school professor's
      first experience with pharmaceutical-company-sponsored research is provided in
      order to examine how funding arrangements can constrain research integrity. The
      case illustrates three significant ways that institutional corruption can occur
      in the research process. First, conflicts of norms between pharmaceutical
      companies, universities, and affiliated teaching hospitals can result in
      compromises and self-censorship. Second, normal behavior is shaped through
      routine interactions. Unethical behaviors can be (or can become) normal behaviors
      when they are produced and reproduced through a network of social interactions.
      Third, funding arrangements can create networks of dependency that structurally
      distort the independence of the academic researcher in favor of the funder's
      interests. More broadly, the case study demonstrates how the social organization
      approach deepens our understanding of the practice of ethics. 

PMID- 24088154
TI  - Key opinion leaders and the corruption of medical knowledge: what the Sunshine
      Act will and won't cast light on.
AB  - The pharmaceutical industry, in its marketing efforts, often turns to "key
      opinion leaders" or "KOLs" to disseminate scientific information. Drawing on the
      author's fieldwork, this article documents and examines the use of KOLs in
      pharmaceutical companies' marketing efforts. Partly due to the use of KOLs, a
      small number of companies with well-defined and narrow interests have inordinate
      influence over how medical knowledge is produced, circulated, and consumed. The
      issue here, as in many other cases of institutional corruption, is that a few
      actors have accumulated the power to shape the information on which many others
      base their decisions. Efforts to address this corruption should focus on
      correcting large imbalances in the current political economy of medical
      knowledge. A sequestration of pharmaceutical research and development on one hand
      from pharmaceutical marketing on the other, though difficult to achieve, would
      address this and many other problems. 

PMID- 24088155
TI  - Drug firms, the codification of diagnostic categories, and bias in clinical
      guidelines.
AB  - The possibility that industry is exerting an undue influence on the culture of
      medicine has profound implications for the profession's public health mission.
      Policy analysts, investigative journalists, researchers, and clinicians have
      questioned whether academic-industry relationships have had a corrupting effect
      on evidence-based medicine. Psychiatry has been at the heart of this epistemic
      and ethical crisis in medicine. This article examines how commercial entities,
      such as pharmaceutical companies, influence psychiatric taxonomy and treatment
      guidelines. Using the conceptual framework of institutional corruption, we show
      that organized psychiatry's dependence on drug firms has led to a distortion of
      science. We describe the current dependency corruption and argue that
      transparency alone is not a solution. We conclude by taking the position that the
      corruption of the evidence base in diagnostic and practice guidelines has
      compromised the informed consent process, and we suggest strategies to address
      this problem. 

PMID- 24088156
TI  - Rooting out institutional corruption to manage inappropriate off-label drug use.
AB  - Prescribing drugs for uses that the FDA has not approved - off-label drug use -
      can sometimes be justified but is typically not supported by substantial evidence
      of effectiveness. At the root of inappropriate off-label drug use lie perverse
      incentives for pharmaceutical firms and flawed oversight of prescribing
      physicians. Typical reform proposals such as increased sanctions for
      manufacturers might reduce the incidence of unjustified off-label use, but they
      do not remove the source of the problem. Public policy should address the cause
      and control the practice. To manage inappropriate off-label drug use, off-label
      prescriptions must be tracked in order to monitor the risks and benefits and the
      manufacturers' conduct. Even more important, reimbursement rules should be
      changed so that manufacturers cannot profit from off-label sales. When off-label
      sales pass a critical threshold, manufacturers should also be required to pay for
      independent testing of the safety and effectiveness of off-label drug uses and
      for the FDA to review the evidence. Manufacturers should also finance, under FDA
      supervision, programs designed to warn physicians and the public about the risks
      of off-label drug use. 

PMID- 24088157
TI  - Physicians under the influence: social psychology and industry marketing
      strategies.
AB  - Pharmaceutical and medical device companies apply social psychology to influence
      physicians' prescribing behavior and decision making. Physicians fail to
      recognize their vulnerability to commercial influences due to self-serving bias,
      rationalization, and cognitive dissonance. Professionalism offers little
      protection; even the most conscious and genuine commitment to ethical behavior
      cannot eliminate unintentional, subconscious bias. Six principles of influence -
      reciprocation, commitment, social proof, liking, authority, and scarcity - are
      key to the industry's routine marketing strategies, which rely on the illusion
      that the industry is a generous avuncular partner to physicians. In order to
      resist industry influence, physicians must accept that they are vulnerable to
      subconscious bias and have both the motivation and means to resist industry
      influence. A culture in which accepting industry gifts engenders shame rather
      than gratitude will reduce conflicts of interest. If greater academic prestige
      accrues to distant rather than close relationships with industry, then a new
      social norm may emerge that promotes patient care and scientific integrity. In
      addition to educating faculty and students about the social psychology underlying
      sophisticated but potentially manipulative marketing and about how to resist it,
      academic medical institutions should develop strong organizational policies to
      counteract the medical profession's improper dependence on industry. 

PMID- 24088158
TI  - From community to commodity: the ethics of pharma-funded social networking sites
      for physicians.
AB  - A growing number of doctors in the United States are joining online professional
      networks that cater exclusively to licensed physicians. The most popular are
      Sermo, with more than 135,000 members, and Doximity, with more than 100,000. Both
      companies claim to offer a valuable service by enabling doctors to "connect" in a
      secure online environment. But their business models raise ethical concerns. The
      sites generate revenue by selling access to their large networks of physician
      users to clients that include global pharmaceutical companies, market research
      and consulting firms, and hedge funds and other investors. In exchange for a fee,
      these clients are offered a variety of tools to monitor, analyze, and solicit
      physicians' opinions. In Sermo's case, clients are also offered opportunities to
      conduct "awareness campaigns" on the site that are aimed at influencing physician
      sentiment about specific drugs and medical devices. In effect, these online
      networks have created an even more efficient means for the pharmaceutical
      industry to track physician sentiment, disseminate messages, and cultivate key
      opinion leaders. This paper argues that the dual nature of these sites (a)
      undermines their integrity and transparency as forums for the exchange of medical
      opinion and (b) presents an ethical conflict for the doctors who use them. 

PMID- 24088160
TI  - Approval and withdrawal of new antibiotics and other antiinfectives in the U.S.,
      1980-2009.
AB  - Numerous reports have noted decreasing numbers of antibiotic approvals. To
      determine the context for this decline, we examined all new molecule entities
      (NMEs) and new biologic licenses (NBLs) approved by the FDA from 1980-2009, and
      compared approval rates of the 61 approved antibiotics to trends in other drug
      classes. We also tracked withdrawals of approved drugs and found more withdrawals
      for antibiotics than other drug classes. After adjusting for drugs subsequently
      withdrawn, the record for antibiotic innovation is less dire than previously
      reported. We also report problems with the quality of the approved antibiotics
      studied. Future policies providing incentives for new antibiotic development
      should not be based on simple numerical targets and key provisions should ensure
      appropriate quality as well as quantity of antibiotic drug innovation. 

PMID- 24088159
TI  - Patient advocacy organizations: institutional conflicts of interest, trust, and
      trustworthiness.
AB  - Patient advocacy organizations (PAOs) advocate for increased research funding and
      policy changes and provide services to patients and their families. Given their
      credibility and political clout, PAOs are often successful in changing policies,
      increasing research funding, and increasing public awareness of medical
      conditions and the problems of their constituents. In order to advance their
      missions, PAOs accept funding, frequently from pharmaceutical firms. Industry
      funding can help PAOs advance their goals but can also create conflicts of
      interest (COI). Research indicates that bias may occur, even among well-meaning
      professionals, when people and organizations have financial COI. Industry funding
      may therefore influence PAOs to act in ways that favor the interests of their
      donors, which may increase the risk of harm to patients. This article extends the
      analysis developed in the Institute of Medicine report, Conflicts of Interest in
      Medical Research, Education, and Practice, and applies the analysis to understand
      PAOs and their relationships with industry. It argues that the preferred goal of
      institutional COI policies should not be to promote trust, but to promote
      trustworthiness and appropriately placed trust. 

PMID- 24088161
TI  - "Something of an adventure": postwar NIH research ethos and the Guatemala STD
      experiments.
AB  - The STD experiments in Guatemala from 1946-1948 have earned a place of infamy in
      the history of medical ethics. But if the Guatemala STD experiments were so
      "ethically impossible," how did the U.S. government approve their funding?
      Although much of the literature has targeted the failings of Dr. John Cutler, we
      focus on the institutional context and research ethos that shaped the outcome of
      the research. After the end of WWII, Dr. Cassius Van Slyke reconstructed the
      federal research contracts process into a grant program. The inaugural NIH study
      section recommended approval of the Guatemala STD experiments at its first
      meeting. The funding and oversight process of the Guatemala research was marked
      with serious conflicts of interest and a lack of oversight, and it was this
      structure, as opposed to merely a maleficent individual, that allowed the
      Guatemala STD experiments to proceed. We conclude that while current research
      regulations are designed to prevent the abuses perpetrated on the subjects of the
      Guatemala STD experiments, it takes a comprehensive understanding of research
      ethics through professional education to achieve the longstanding ideal of the
      responsible investigator, and ensure ethical research under any regulatory
      scheme. 

PMID- 24088162
TI  - Ethical quandaries in gamete-embryo cryopreservation related to oncofertility.
AB  - While cancer rates continue to increase, therapy has dramatically decreased the
      mortality rates. The increased efficacy of current therapies may unfortunately
      have profound toxic effects on gamete function in both adolescent and
      reproductive age groups, with infertility as an expected consequence of cancer
      therapy. Significant progress in the advancement of fertility preservation
      therapies provides realistic options for future fertility in cancer survivors.
      However, a number of challenging issues need to be considered when presenting
      fertility preservation options. This overview highlights some of these
      considerations including religious-cultural-ethical values, access to care and
      cost of services, developmental capacity and consent, and posthumous
      reproduction. 

PMID- 24088163
TI  - Producing knowledge about racial differences: tracing scientists' use of "race"
      and "ethnicity" from grants to articles.
AB  - The research and publication practices by which scientists produce biomedical
      knowledge about race and ethnicity remain largely unexamined, and most of the
      existing research looks at the knowledge production process at a single point in
      time. In light of this, we specifically focus on the questions of whether and in
      what ways researchers' discussions of race and ethnicity change over the course
      of the research process by comparing grant proposals to published articles. Using
      content analysis, we investigated the use of race and ethnicity in 72 grants
      funded by the National Cancer Institute of the National Institutes of Health
      between 1990 and 1999 and 144 matched articles published between 1996 and 2010,
      tracing the production of biomedical knowledge from study design to published
      findings. This is also the first study to look at whether the NIH Inclusion
      Mandate, which went into effect in June of 1994, changed the way investigators
      research and write about racial and ethnic differences. In following this
      knowledge production process, we explore how scientists "deliver" on their
      research proposal goals. In addition, we provide insight into whether and how
      state policies directed at guiding research practices can shape output. 

PMID- 24088164
TI  - Epigenetic exceptionalism.
AB  - This article considers the distinctive features of epigenetics and discusses
      whether, as a matter of ethics and law, epigenetics should be considered separate
      from genetics. 

PMID- 24088165
TI  - Major trends in public health law and practice: a network national report.
AB  - Since its inception in September 2010, the Network for Public Health Law has
      responded to hundreds of public health legal technical assistance claims from
      around the country. Based on a review of these data, a series of major trends in
      public health practice and the law are analyzed, including issues concerning: the
      Affordable Care Act, tobacco control, emergency legal preparedness, health
      information privacy, food policy, vaccination, drug overdose prevention, sports
      injury law, public health accreditation, and maternal breastfeeding. These and
      other emerging themes in public health law demonstrate the essential role of law
      and practice in advancing the public's health. 

PMID- 24088166
TI  - Influence of degree of gas saturation on sonochemiluminescence intensity
      resulting from microfluidic reactions.
AB  - This work examined the effects of dissolved gas degree of saturation (DOS) on
      sonochemical reaction yields in both a one-dimensional (1D) microspace and a
      three-dimensional (3D) millimeter-sized space. The extent of each reaction was
      monitored by measuring sonochemiluminescence (SCL) intensity at 213 kHz. The
      results demonstrated that, at relatively low levels of power density, selecting a
      solution DOS in the supersaturation range at atmospheric pressure resulted in
      higher yields per unit volume in the 1D space compared to that obtained from the
      3D space. This effect is attributed to a decrease in the cavitation threshold of
      the 1D reaction system since, at low power density, the 1D space represents a
      more homogeneous reaction volume. Comparing the highest SCL intensity levels
      obtained from the 3D and 1D reactions shows that enhancing the reaction yield in
      the 1D space requires higher DOS values than are required to generate elevated
      yields in the 3D space. The 3D space contains a greater concentration of bubbles
      than the 1D space, but many of these are ineffective at promoting the reaction.
      Thus, reactions in the 3D environment require not only the application of higher
      power density levels but also a lower DOS, so as to allow the bubbles to undergo
      the violent pulsations necessary to facilitate the sonochemical reaction. 

PMID- 24088167
TI  - Persistent anosmia in a traumatic brain injury patient: role of orbitofrontal
      cortex.
AB  - BACKGROUND: The olfactory loss due to traumatic brain injury is a common clinical
      condition. The understanding of the cortical areas involved in ability to detect,
      discriminate and identify the odours is still limited. However, it has been shown
      that the orbitofrontal cortex (OFC) is involved in the discrimination and
      recognition of odours and in particular the right OFC has a dominant role in the
      central processing of smell. METHOD: This study used the Sniffin' Sticks Test to
      evaluate olfactory function of a 40-year-old female with persistent post
      traumatic anosmia and to have a objective measure method for the follow-up.
      RESULTS: A marked decrease in the ability to identify and discriminate odours was
      found. On the other hand the ability to perceive the odours was little
      compromised. A cerebral Magnetic Resonance Imaging, performed 10 months after the
      trauma, showed the presence of a post-traumatic scarring in the right frontal
      lobe involving the OFC. CONCLUSIONS: In this case of post-traumatic anosmia, the
      ability to perceive and recognize odours does not seem to be compromised in the
      same measure. It is postulated that the post-traumatic outcomes, involving areas
      of multisensory integration such as the OFC, have an important pathogenetic role
      in the loss of ability to recognize and discriminate odours.

PMID- 24088171
TI  - Molecular basis for the long duration of action and kinetic selectivity of
      tiotropium for the muscarinic M3 receptor.
AB  - Antagonizing the human M3 muscarinic receptor (hM3R) over a long time is a key
      feature of modern bronchodilating COPD drugs aiming at symptom relief. The long
      duration of action of the antimuscarinic drug tiotropium and its kinetic subtype
      selectivity over hM2R are investigated by kinetic mapping of the binding site and
      the exit channel of hM3R. Hence, dissociation experiments have been performed
      with a set of molecular matched pairs of tiotropium on a large variety of mutated
      variants of hM3R. The exceedingly long half-life of tiotropium (of more than 24
      h) is attributed to interactions in the binding site; particularly a highly
      directed interaction of the ligands' hydroxy group with an asparagine
      (N508(6.52)) prevents rapid dissociation via a snap-lock mechanism. The kinetic
      selectivity over hM2R, however, is caused by differences in the electrostatics
      and in the flexibility of the extracellular vestibule. Extensive molecular
      dynamics simulations (several microseconds) support experimental results. 

PMID- 24088168
TI  - Profiling deacetylase activities in cell lysates with peptide arrays and SAMDI
      mass spectrometry.
AB  - The development of arrays that can profile molecular activities in cells is
      important to understanding signaling pathways in normal and pathological
      settings. While oligonucleotide arrays are now routinely used to profile global
      gene expression, there is still a lack of tools for profiling enzyme activities
      in cell lysates. This paper describes the combination of peptide arrays formed on
      self-assembled monolayers and mass spectrometry to provide a label-free approach
      for identifying patterns of enzyme activities in cell lysates. The approach is
      demonstrated by profiling lysine deacetylase (KDAC) activities in cell lysates of
      the CHRF megakaryocytic (Mk) cell line. Class-specific deacetylase inhibitors
      were used to show that terminal Mk differentiation of CHRF cells is marked by a
      pronounced decrease in sirtuin activity and by little change in activity of KDACs
      1-11. This work establishes a platform that can be used to identify changes in
      global activity profiles of cell lysates for a wide variety of enzymatic
      activities. 

PMID- 24088172
TI  - POP-pincer silyl complexes of group 9: rhodium versus iridium.
AB  - 9,9-Dimethyl-4,5-bis(diisopropylphosphino)xanthene (xant(P(i)Pr2)2) derivatives
      RhCl{xant(P(i)Pr2)2} (1) and I rHCl{xant(P(i)Pr2)[(i)PrPCH(Me) CH2]} (2) react
      with diphenylsilane and triethylsilane to give the saturated d(6)-compounds
      RhHCl(SiR3){xant(P(i)Pr2)2} (SiR3 = SiHPh2 (3), SiEt3 (4)) and
      IrHCl(SiR3){xant(P(i)Pr2)2} (SiR3 = SiHPh2 (5), SiEt3 (6)). Complexes 3 and 5
      undergo a Cl/H position exchange process via the MH{xant(P(i)Pr2)2} (M = Rh (8),
      Ir (E)) intermediates. The rhodium complex 3 affords the square planar d(8)-silyl
      derivative Rh(SiClPh2){xant(P(i)Pr2)2} (7), whereas the iridium derivative 5
      gives IrH2(SiClPh2){xant(P(i)Pr2)2} (9), which is stable. In agreement with the
      formation of 7, the reactions of 8 with silanes are a general method to prepare
      square planar d(8)-rhodium-silyl derivatives. Thus, the addition of
      triethylsilane and triphenylsilane to 8 initially leads to the dihydrides
      RhH2(SiR3){xant(P(i)Pr2)2} (SiR3 = SiEt3 (10), SiPh3 (11)), which lose molecular
      hydrogen to afford Rh(SiR3){xant(P(i)Pr2)2} (SiR3 = SiEt3 (12), SiPh3 (13)).
      Treatment of 7 with NaBAr(F)4.2H2O leads to the cationic five-coordinate d(6)
      species [RhH{Si(OH)Ph2}{xant(P(i)Pr2)2}]BAr(F)4 (14) through a silylene
      intermediate. According to the participation of the latter in the formation of
      14, this cation is an efficient catalyst precursor for the monoalcoholysis of
      diphenylsilane with a wide range of alcohols, reaching turnover frequencies at
      50% of conversion between 4000 and 76 500 h(-1). The X-ray structures of 3, 6, 7,
      9, 12, and 14 are also reported. 

PMID- 24088174
TI  - Hereditary spherocytosis and wandering spleen.

PMID- 24088173
TI  - Prolonged cigarette smoke exposure alters mitochondrial structure and function in
      airway epithelial cells.
AB  - BACKGROUND: Cigarette smoking is the major risk factor for COPD, leading to
      chronic airway inflammation. We hypothesized that cigarette smoke induces
      structural and functional changes of airway epithelial mitochondria, with
      important implications for lung inflammation and COPD pathogenesis. METHODS: We
      studied changes in mitochondrial morphology and in expression of markers for
      mitochondrial capacity, damage/biogenesis and fission/fusion in the human
      bronchial epithelial cell line BEAS-2B upon 6-months from ex-smoking COPD GOLD
      stage IV patients to age-matched smoking and never-smoking controls. RESULTS: We
      observed that long-term CSE exposure induces robust changes in mitochondrial
      structure, including fragmentation, branching and quantity of cristae. The
      majority of these changes were persistent upon CSE depletion. Furthermore, long
      term CSE exposure significantly increased the expression of specific
      fission/fusion markers (Fis1, Mfn1, Mfn2, Drp1 and Opa1), oxidative
      phosphorylation (OXPHOS) proteins (Complex II, III and V), and oxidative stress
      (Mn-SOD) markers. These changes were accompanied by increased levels of the pro
      inflammatory mediators IL-6, IL-8, and IL-1beta. Importantly, COPD primary
      bronchial epithelial cells (PBECs) displayed similar changes in mitochondrial
      morphology as observed in long-term CSE-exposure BEAS-2B cells. Moreover,
      expression of specific OXPHOS proteins was higher in PBECs from COPD patients
      than control smokers, as was the expression of mitochondrial stress marker PINK1.
      CONCLUSION: The observed mitochondrial changes in COPD epithelium are potentially
      the consequence of long-term exposure to cigarette smoke, leading to impaired
      mitochondrial function and may play a role in the pathogenesis of COPD.

PMID- 24088175
TI  - Effect of Heterotheca inuloides essential oil on rat cytoskeleton articular
      chondrocytes.
AB  - Osteoarthritis is characterised by progressive loss of articular cartilage
      through the increase of catabolic metalloproteinases, and chondrocyte
      cytoskeleton disruption has also been reported. In this regard, we studied the
      effect of Heterotheca inuloides essential oil (HIEO) on the distribution and
      immunolocalisation of actin, vimentin and tubulin of chondrocytes from cultured
      rat articular cartilage explants in the presence of the cytoskeleton disassembly
      agent acrylamide. After 48 h, chondrocytes treated with acrylamide showed changes
      in actin immunolocalisation and shrinkage, loss of tubulin compartmentalisation
      and vimentin collapse and redistribution. However, the immunostaining pattern of
      these three proteins in acrylamide- and HIEO-treated chondrocytes simultaneously
      retained their typical characteristics. These results suggest that HIEO promotes
      protein cytoskeleton reorganisation without providing a preventive effect of
      acrylamide-associated disassembly. However, it is also possible that HIEO
      prevents vimentin disorganisation by chemical interaction with acrylamide.

PMID- 24088177
TI  - Assessment of neuropsychological late effects in survivors of childhood leukemia.
AB  - The neurologic dysfunctions caused by treatment may affect health and quality of
      life in survivors of childhood leukemia. The objective of this study was to
      identify the neuropsychological late effects of leukemia treatment to provide an
      assessment about the degree and incidence of these late effects. Neurological and
      ophtalmological examination, cranial magnetic resonance imaging (MRI), auditory
      and neurocognitive tests, and questionnaires of quality of life were performed to
      44 acute leukemia survivors at least 5 years after diagnosis. Median time since
      completion of chemotherapy was 7.5 years (2-18) and median age at the time of the
      study was 16.4 years (8-31). At least one or more late effects detected by
      physical examination (PE), neurological tests, or neurocognitive tests
      encountered in 80% of the patients, and 64% of the patients specified at least
      one complaint in the quality of life questionnaire. MRI revealed pathological
      findings in 18% and electroencephalogram (EEG) abnormalities were present in 9%
      of the patients. Evaluation of total intelligence scores revealed that 30% of
      patients' IQ scores were <80 and 70% of the patients' scores demonstrated
      neurocognitive dysfunctions. The patients >6 years at the time of diagnosis were
      found to have more psychological problems and higher rates of smoking and alcohol
      consumption. The most frequent complaint was headache and the most common problem
      in school was denoted as difficulty in concentration. Our study demonstrated that
      most of the survivors of childhood leukemia are at risk of developing
      neuropsycological late effects. 

PMID- 24088176
TI  - A critical role for suppressor of cytokine signalling 3 in promoting M1
      macrophage activation and function in vitro and in vivo.
AB  - Macrophages respond to their microenvironment and develop polarized functions
      critical for orchestrating appropriate inflammatory responses. Classical (M1)
      activation eliminates pathogens while alternative (M2) activation promotes
      regulation and repair. M1 macrophage activation is strongly associated with
      suppressor of cytokine signalling 3 (SOCS3) expression in vitro, but the
      functional consequences of this are unclear and the role of SOCS3 in M1
      macrophage polarization in vivo remains controversial. To address these
      questions, we defined the characteristics and function of SOCS3-expressing
      macrophages in vivo and identified potential mechanisms of SOCS3 action.
      Macrophages infiltrating inflamed glomeruli in a model of acute nephritis show
      significant up-regulation of SOCS3 that co-localizes with the M1-activation
      marker, inducible nitric oxide synthase. Numbers of SOCS3(hi) -expressing, but
      not SOCS1(hi) -expressing, macrophages correlate strongly with the severity of
      renal injury, supporting their inflammatory role in vivo. Adoptive transfer of
      SOCS3-short interfering RNA-silenced macrophages into a peritonitis model
      demonstrated the importance of SOCS3 in driving production of pro-inflammatory IL
      6 and nitric oxide, while curtailing expression of anti-inflammatory IL-10 and
      SOCS1. SOCS3-induced pro-inflammatory effects were due, at least in part, to its
      role in controlling activation and nuclear accumulation of nuclear factor-kappaB
      and activity of phosphatidylinositol 3-kinase. We show for the first time that
      SOCS3 also directs the functions of human monocyte-derived macrophages, including
      efficient M1-induced cytokine production (IL-1beta, IL-6, IL-23, IL-12),
      attenuated signal transducer and activator of transcription 3 activity and
      ability of antigen-loaded macrophages to drive T-cell responses. Hence, M1
      associated SOCS3 was a positive regulator of pro-inflammatory responses in our
      rodent models and up-regulated SOCS3 is essential for effective M1-macrophage
      activation and function in human macrophages. 

PMID- 24088178
TI  - Multifunctional nanorods serving as nanobridges to modulate T cell-mediated
      immunity.
AB  - Electrodeposited nanorods serving as multivalent bridges were fabricated and
      surface-decorated with ligands for immune cells. Gold and nickel solutions were
      sequentially electrodeposited on nanoporous anodized disc templates and the
      template was dissolved to retrieve bisegmented nanorods with different lengths.
      Gold and nickel segmented nanorods were surface-immobilized with mannose and RGD
      peptides to prepare immune-cell recruiting nanorods. Surface-functionalization of
      nanorods were confirmed by fluorescence-labeling of each ligands and confocal
      microscopy. Dendritic cells and T cells were co-incubated with the surface
      functionalized nanorods, and the proximity between the nanorods and the immune
      cells was visualized by variable pressure scanning electron microscopy and
      confocal microscopy. The long nanorods were associated with the immune cells,
      whereas the shorter nanorods were rather endocytosed by cells, suggesting a
      feasibility of the longer nanorods as bridging for the cells. Cytokine releases
      from the immune cells were monitored by cultivating lipopolysaccharide-activated
      dendritic cells with T cells. Interleukine-2 and interferon-gamma release
      profiles showed a strong correlation with the length of the nanorod, where the 4
      MUm nanorods induced the highest levels of cytokine release compared to 1 or 2
      MUm nanorods. Thus, we concluded that the proximity of the immune cells increased
      by bridging the immune cells with the nanobridging system, which subsequently
      increased cytokine release by facilitating the antigen presentation process. 

PMID- 24088179
TI  - Laboratory studies on secondary organic aerosol formation from crude oil vapors.
AB  - Airborne measurements of aerosol composition and gas phase compounds over the
      Deepwater Horizon (DWH) oil spill in the Gulf of Mexico in June 2010 indicated
      the presence of high concentrations of secondary organic aerosol (SOA) formed
      from organic compounds of intermediate volatility. In this work, we investigated
      SOA formation from South Louisiana crude oil vapors reacting with OH in a
      Potential Aerosol Mass flow reactor. We use the dependence of evaporation time on
      the saturation concentration (C*) of the SOA precursors to separate the
      contribution of species of different C* to total SOA formation. This study shows
      consistent results with those at the DWH oil spill: (1) organic compounds of
      intermediate volatility with C* = 10(5)-10(6) MUg m(-3) contribute the large
      majority of SOA mass formed, and have much larger SOA yields (0.37 for C* = 10(5)
      and 0.21 for C* = 10(6) MUg m(-3)) than more volatile compounds with C*>=10(7)
      MUg m(-3), (2) the mass spectral signature of SOA formed from oxidation of the
      less volatile compounds in the reactor shows good agreement with that of SOA
      formed at DWH oil spill. These results also support the use of flow reactors
      simulating atmospheric SOA formation and aging. 

PMID- 24088180
TI  - Flu-like symptoms following radiofrequency liver transection: a new variety of
      the post-radiofrequency syndrome.
AB  - BACKGROUND/AIMS: The aim of our study was to determine whether post
      radiofrequency syndrome may also develop following hepatectomy using saline
      cooled radiofrequency coagulation. METHODS: We retrospectively reviewed 95
      consecutive patients who underwent 110 liver resections between May 2000 and
      September 2012. We stated that 80.9% of the resections were carried out employing
      the saline-cooled radiofrequency device. All medical records were searched for
      the occurrence of flu-like symptoms, without evidence of sepsis or infection, in
      the first two postoperative weeks. RESULTS: Eleven patients (11.5%) developed flu
      like symptoms after hepatectomy without evidence of sepsis or infection. All
      their hepatectomies were performed employing the saline-cooled radiofrequency
      probe (p = .089), and all cases but one appeared following colorectal liver
      metastases surgery (p = .042). Eight of them were readmitted to the hospital
      because of their symptoms. In all 11 cases, a fluid collection was present, 8 of
      them with gas presence. Nine patients underwent a percutaneous drainage whose
      cultures were negative. Ten patients recovered without treatment or with the
      intake of nonsteroidal anti-inflammatory drugs within 1 week, but one patient
      developed a secondary infection with gram-positive bacteria after percutaneous
      drainages that prolonged his hospital stay. CONCLUSION: Liver splitting using
      saline-cooled radiofrequency coagulation may cause postoperative symptoms that
      may mimic surgical site infection. Surgeons employing this device should keep
      this in mind to avoid potentially unwarranted treatments that may be unnecessary,
      expensive, and even harmful.

PMID- 24088181
TI  - Parent education for adults with intellectual disability: A review and
      suggestions for future research.
AB  - OBJECTIVE: This review evaluates research regarding parent education
      interventions for adults with an intellectual disability (ID). METHODS:
      Electronic database and ancestral searches identified 13 studies published
      between 1994 and 2012. The results of these studies are discussed in relation to
      (a) participants and settings; (b) general intervention procedures, (c)
      programmed antecedent stimuli to occasion parent behaviour; (d) targeted
      behaviours; (e) programmed consequence(s) for parent behaviour; and (f) the
      presence of generalization and maintenance strategies. RESULTS: In the majority
      of reviewed studies, intervention components lacked operational definitions
      appropriate for replication and direct observation of child outcomes were often
      not included as a dependent variable. Also, most interventions did not include
      steps to promote the generalization of skills to different stimuli or settings
      although the majority assessed the maintenance of targeted skills. CONCLUSION: In
      consideration of these findings, several relevant areas for future research are
      proposed.

PMID- 24088182
TI  - Foldameric alpha/beta-peptide analogs of the beta-sheet-forming antiangiogenic
      anginex: structure and bioactivity.
AB  - The principles of beta-sheet folding and design for alpha-peptidic sequences are
      well established, while those for sheet mimetics containing homologated amino
      acid building blocks are still under investigation. To reveal the structure
      function relations of beta-amino-acid-containing foldamers, we followed a top
      down approach to study a series of alpha/beta-peptidic analogs of anginex, a beta
      sheet-forming antiangiogenic peptide. Eight anginex analogs were developed by
      systematic alpha -> beta(3) substitutions and analyzed by using NMR and CD
      spectroscopy. The foldamers retained the beta-sheet tendency, though with a
      decreased folding propensity. beta-Sheet formation could be induced by a micellar
      environment, similarly to that of the parent peptide. The destructuring effect
      was higher when the alpha -> beta(3) exchange was located in the beta-sheet core.
      Analysis of the beta-sheet stability versus substitution pattern and the local
      conformational bias of the bulky beta(3)V and beta(3)I residues revealed that a
      mismatch between the H-bonding preferences of the alpha- and beta-residues played
      a minor role in the structure-breaking effect. Temperature-dependent CD and NMR
      measurements showed that the hydrophobic stabilization was scaled-down for the
      alpha/beta-peptides. Analysis of the biological activity of the foldamer peptides
      showed that four anginex derivatives dose-dependently inhibited the proliferation
      of a mouse endothelial cell line. The alpha -> beta(3) substitution strategy
      applied in this work can be a useful approach to the construction of bioactive
      beta-sheet mimetics with a reduced aggregation tendency and improved
      pharmacokinetic properties. 

PMID- 24088183
TI  - Health effects of benzene exposure among children following a flaring incident at
      the British Petroleum Refinery in Texas City.
AB  - Human exposure to benzene is associated with multiple adverse health effects
      leading to hematological malignancies. The objective of this retrospective study
      was to evaluate the health consequences of benzene exposure in children following
      a flaring incident at the British petroleum (BP) refinery in Texas City, Texas.
      The study included children aged <17 years who had been exposed and unexposed to
      benzene. Using medical charts, clinical data including white blood cell (WBC)
      counts, platelets counts, hemoglobin, hematocrit, blood urea nitrogen (BUN),
      creatinine, alkaline phosphatase (ALP), aspartate amino transferase (AST),
      alanine amino transferase (ALT), and somatic symptom complaints by the children
      exposed to benzene were reviewed and analyzed. A total of 312 subjects (benzene
      exposed, n = 157 and unexposed, n = 155) were included. Hematologic analysis
      showed that WBC counts were significantly decreased in benzene-exposed children
      compared with the unexposed children (6.8 +/- 2.1 versus 7.3 +/- 1.7, P = .022).
      Conversely, platelet (X 10(3) per MUL) counts were increased significantly in the
      benzene-exposed group compared with the unexposed group (278.4 +/- 59.9 versus
      261.6 +/- 51.7, P = .005). Similarly, benzene-exposed children had significantly
      higher levels of ALP (183.7+/- 95.6 versus 165 +/- 70.3 IU/L, P = .04), AST (23.6
      +/- 15.3 versus 20.5 +/- 5.5 IU/L, P = .015), and ALT (19.2 +/- 7.8 versus 16.9
      +/- 6.9 IU/L, P = .005) compared with the unexposed children. Together, the
      results of the study reveal that children exposed to benzene experienced
      significantly altered blood profiles, liver enzymes, and somatic symptoms
      indicating that children exposed to benzene are at a higher risk of developing
      hepatic or blood related disorders.

PMID- 24088185
TI  - Rapid replication and facile modulation of subwavelength antireflective polymer
      film using injection nanomolding and optical property of multilayer coatings.
AB  - A rapid, cost-effective and high-throughput process for nanotexturing
      subwavelength structures with high uniformity using the polycarbonate (PC) is
      realized via injection nanomolding. The process enables the precise control of
      nanohole array (NHA) surface topography (nanohole depth, diameter, and
      periodicity) over large areas thereby presenting a highly versatile platform for
      fabricating substrates with user-defined, functional performance. Specifically,
      the optical property of the PC substrates were systematically characterized and
      tuned through the modulation of the depths of NHA. The aspect ratio submicron
      holes can be easily modulated and experimentally proven by simply adjusting the
      molding temperature. The nanotextured depths were reliably fabricated in the
      range of 200 to 400 nm with a period of approximately 700 nm. The fabricated PC
      films can reduce the reflectivity from an original bare film of 10.2% and 8.9% to
      1.4% and 2.1% with 400-nm depth of nanoholes at the wavelength of 400 and 550 nm,
      respectively. Compared with conventional moth-like nanostructures with nanopillar
      arrays with heights adjustable only by an etching process, this paper proposes a
      facile route with submicron holes to achieve a similar antireflective function,
      with a significantly reduced time and facile height modulation capability.
      Furthermore, the effects of multilayer coatings of dielectric and metallic layers
      on the nanomolded NHA have been performed and potential sensing application is
      explored. 

PMID- 24088184
TI  - Cytotoxicity of Elaoephorbia drupifera and other Cameroonian medicinal plants
      against drug sensitive and multidrug resistant cancer cells.
AB  - BACKGROUND: Multidrug resistance (MDR) is a major hurdle for cancer treatment
      worldwide and accounts for chemotherapy failure in over 90% of patients with
      metastatic cancer. Evidence of the cytotoxicity of Cameroonian plants against
      cancer cell lines including MDR phenotypes is been intensively and progressively
      provided. The present work was therefore designed to evaluate the cytotoxicity of
      the methanol extracts of twenty-two Cameroonian medicinal plants against
      sensitive and MDR cancer cell lines. METHODS: The methanol maceration was used to
      obtain the crude plant extracts whilst the cytotoxicity of the studied extracts
      was determined using a resazurin reduction assay. RESULTS: A preliminary assay on
      leukemia CCRF-CEM cells at 40 MUg/mL shows that six of the twenty plant extract
      were able to enhance less than 50% of the growth proliferation of CCRF-CEM cells.
      These include Crinum zeylanicum (32.22%), Entada abyssinica (34.67%),
      Elaoephorbia drupifera (35.05%), Dioscorea bulbifera (45.88%), Eremomastax
      speciosa (46.07%) and Polistigma thonningii (45.11%). Among these six plants, E.
      drupifera showed the best activity with IC50 values below or around 30 MUg/mL
      against the nine tested cancer cell lines. The lowest IC50 value of 8.40 MUg/mL
      was recorded with the extract of E. drupifera against MDA-MB231 breast cancer
      cell line. The IC50 values below 10 MUg/mL were recorded with the extracts of E.
      drupifera against MDA-MB231 breast cancer cells, C. zeylanicum against HCT116
      p53+/+ and HCT116p53-/- colon cancer cells and E. abyssinica against HCT116
      p53+/+ cells. CONCLUSION: The results of the present study provide evidence of
      the cytotoxic potential of some Cameroonian medicinal plants and a baseline
      information for the potential use of Elaoephorbia drupifera in the treatment of
      sensitive and drug-resistant cancer cell lines.

PMID- 24088186
TI  - Single dose darbepoetin alfa is useful in reducing red cell transfusions in
      leukemic children receiving chemotherapy.
AB  - The role of erythropoiesis-stimulating agents (ESAs) in the management of
      chemotherapy-induced anemia (CIA) is becoming increasingly recognized in the
      field of medical oncology, with paucity of data in pediatrics. We evaluated the
      efficacy and tolerability of a single-dose darbepoetin alfa, a long-acting ESA,
      given to 35 pediatric acute lymphoblastic leukemia (ALL) children during
      induction chemotherapy. Compared to a retrospective control group, the studied
      patients have required significantly less units of packed red blood cells (0.88
      units/patient in the studied group versus 2.04 units in controls), with no major
      side effects. We recommend further prospective double-blinded studies with more
      tailored dosing regimens in pediatric ALL cases and solid tumors. 

PMID- 24088187
TI  - BK viremia and polyomavirus nephropathy in 352 kidney transplants; risk factors
      and potential role of mTOR inhibition.
AB  - BACKGROUND: Polyomavirus BK nephropathy (PyVAN) remains an important cause of
      early graft dysfunction and graft loss in kidney transplantation. METHODS: In
      this retrospective, single centre cohort study we studied the incidence and
      outcome of BK viral infection in 352 patients transplanted in 2008-2011. RESULTS:
      During follow-up viral replication was detected in 48 patients (13.6%); 22
      patients (6.2%) had biopsy proven PyVAN.In multivariate logistic regression
      analyses risk factors for BK-viremia were lack of enrolment into randomized
      controlled trials (RCTs), biopsy proven acute rejections, cytomegaly virus (CMV)
      serostatus of both donor and recipient and previous transplantation.In patients
      without PyVAN reduction or switch of immunosuppression was associated with rapid
      viral clearance and stable graft function. In contrast, in most patients with
      PyVAN graft function deteriorated and 5 patients prematurely lost their
      allograft. Switch of immunosuppression to a low dose cyclosporine plus mTOR
      inhibitor based regimen in patients with PyVAN was safe, well tolerated and
      tended to be associated with a better short-term outcome in terms of graft
      function compared to reduction of existing immunosuppression alone. CONCLUSIONS:
      With the lack of licensed anti-polyoma viral drugs reduction or conversion of
      immunosuppression remains the mainstay of therapy in patients with PyVAN. The
      combination of low dose cyclosporine plus mTOR inhibition appears to be safe and
      warrants further investigation.

PMID- 24088188
TI  - V-Phaser 2: variant inference for viral populations.
AB  - BACKGROUND: Massively parallel sequencing offers the possibility of
      revolutionizing the study of viral populations by providing ultra deep sequencing
      (tens to hundreds of thousand fold coverage) of complete viral genomes. However,
      differentiation of true low frequency variants from sequencing errors remains
      challenging. RESULTS: We developed a software package, V-Phaser 2, for inferring
      intrahost diversity within viral populations. This program adds three major new
      methodologies to the state of the art: a technique to efficiently utilize paired
      end read data for calling phased variants, a new strategy to represent and infer
      length polymorphisms, and an in line filter for erroneous calls arising from
      systematic sequencing artifacts. We have also heavily optimized memory and run
      time performance. This combination of algorithmic and technical advances allows V
      Phaser 2 to fully utilize extremely deep paired end sequencing data (such as
      generated by Illumina sequencers) to accurately infer low frequency intrahost
      variants in viral populations in reasonable time on a standard desktop computer.
      V-Phaser 2 was validated and compared to both QuRe and the original V-Phaser on
      three datasets obtained from two viral populations: a mixture of eight known
      strains of West Nile Virus (WNV) sequenced on both 454 Titanium and Illumina
      MiSeq and a mixture of twenty-four known strains of WNV sequenced only on 454
      Titanium. V-Phaser 2 outperformed the other two programs in both sensitivity and
      specificity while using more than five fold less time and memory. CONCLUSIONS: We
      developed V-Phaser 2, a publicly available software tool (V-Phaser 2 can be
      accessed via: http://www.broadinstitute.org/scientific
      community/science/projects/viral-genomics/v-phaser-2 and is freely available for
      academic use) that enables the efficient analysis of ultra-deep sequencing data
      produced by common next generation sequencing platforms for viral populations.

PMID- 24088189
TI  - The effect of Boswellia Serrata on neurorecovery following diffuse axonal injury.
AB  - OBJECTIVES: This pilot trial was conducted to establish whether Boswellia Serrata
      (BS), a traditional herbal medicine, could improve the outcome of patients who
      have diffuse axonal injury (DAI). METHODS: In total, 38 patients with pure DAI
      were enrolled in this 12-week, double-blind, randomized, cross-over study. The
      patients were randomly assigned to receive either placebo (group A, n = 20) or BS
      capsules (group B, n = 18) for 6 weeks and then switched to the other
      intervention for another 6 weeks. The disability rating scale (DRS) was used to
      assess the outcome at 2-, 6- and 12-weeks post-trauma. RESULTS: A non-significant
      trend for improvement of DRS total scores was observed after the use of BS.
      Regarding the DRS sub-scores, however, there was significant improvement in
      'cognitive ability to self-care' during the second 6 weeks in group A on BS
      compared to an insignificant spontaneous recovery in group B during the same
      period on placebo. Moreover, both groups experienced a close-to-significant
      increase in the cognitive function-related items of the DRS during the periods
      they were on BS. The reported adverse events were all of mild quality and had
      similar frequency between the groups. CONCLUSION: These results suggest that BS
      resin does not significantly affect general outcome, but may enhance the
      cognitive outcome of patients with DAI.

PMID- 24088190
TI  - Thiazolopyridine ureas as novel antitubercular agents acting through inhibition
      of DNA Gyrase B.
AB  - A pharmacophore-based search led to the identification of thiazolopyridine ureas
      as a novel scaffold with antitubercular activity acting through inhibition of DNA
      Gyrase B (GyrB) ATPase. Evaluation of the binding mode of thiazolopyridines in a
      Mycobacterium tuberculosis (Mtb) GyrB homology model prompted exploration of the
      side chains at the thiazolopyridine ring C-5 position to access the
      ribose/solvent pocket. Potent compounds with GyrB IC50 <= 1 nM and Mtb MIC <= 0.1
      MUM were obtained with certain combinations of side chains at the C-5 position
      and heterocycles at the C-6 position of the thiazolopyridine core. Substitutions
      at C-5 also enabled optimization of the physicochemical properties.
      Representative compounds were cocrystallized with Streptococcus pneumoniae (Spn)
      ParE; these confirmed the binding modes predicted by the homology model. The
      target link to GyrB was confirmed by genetic mapping of the mutations conferring
      resistance to thiazolopyridine ureas. The compounds are bactericidal in vitro and
      efficacious in vivo in an acute murine model of tuberculosis. 

PMID- 24088191
TI  - Pituitary apoplexy induced by Gonadotropin-releasing hormone agonists for
      treating prostate cancer-report of first Asian case.
AB  - We present the first Asian case of a 77-year-old man who developed pituitary
      apoplexy (PA) soon after gonadotropin-releasing hormone agonist (GnRHa)
      (leuprorelin) injection to treat prostate cancer. Headache, ophthalmoplegia,
      visual field deficit, nausea, and vomiting are the typical characteristics of
      pituitary apoplexy. Though the occurrence rate is rare, the consequence of this
      condition can vary from mild symptoms such as headache to life-threatening
      scenarios like conscious change. Magnetic resonance imaging is the best imaging
      modality to detect PA and sublabial trans-sphenoid pituitary tumor removal can
      resolve most of PA symptoms and is so far the best solution in consensus. We also
      review 11 previous reported cases receiving GnRHa for androgen deprivation
      therapy of prostate cancer, and hope to alert clinicians to use GnRHa with
      caution. 

PMID- 24088192
TI  - The application of electromagnetically guided post-pyloric feeding tube placement
      in critically ill patients.
AB  - BACKGROUND: Critically ill patients who demonstrate impaired gastric emptying
      benefit from post-pyloric enteral nutrition. However, correct placement of post
      pyloric tube is challenging. METHODS: In a retrospective, single center study,
      142 critically ill patients were enrolled using electromagnetic technology. Our
      specialized team placed all post-pyloric tubes. Metoclopramide (10 mg) was
      infused 15 min prior to tube placement, and the tube tip location was confirmed
      by X-ray. Success rate for post-pyloric placement, implant time, time until EN
      initiation, and placement-related complications were measured. RESULTS: 135 tubes
      in 142 patients were successfully placed during the first attempt, including 101
      jejunal and 34 duodenal tubes. The average placement time was 20.12 min. The time
      from the physician order to the first tube placement attempt and EN
      administration was 3.6 and 7.5 hr, respectively. No placement-related
      complications were observed. CONCLUSIONS: Electromagnetic technology facilitates
      safe and effective post-pyloric feeding tube placement at the bedside in
      critically ill patients with impaired gastric emptying.

PMID- 24088193
TI  - Nutritional supplement products: Does the label information influence purchasing
      decisions for the physically active?
AB  - BACKGROUND: The increase in sales of nutritional supplement globally can be
      attributed, in part, to aggressive marketing by manufacturers, rather than
      because the nutritional supplements have become more effective. Furthermore, the
      accuracy of the labelling often goes unchallenged. Therefore, any effects of the
      supplement, may be due to contaminants or adulterants in these products not
      reflected on the label. METHODS: A self-administered questionnaire was used to
      determine how consumers of nutritional supplements acquired information to assist
      their decision-making processes, when purchasing a product. The study was
      approved by the University of Cape Town, Faculty of Health Sciences Human
      Research Ethics Committee. The questionnaire consisted of seven, closed and open
      ended questions. The participants were asked to respond to the questions
      according to a defined list of statements. A total of 259 participants completed
      and returned questionnaires. The data and processing of the returned
      questionnaires was captured using Windows-based Microsoft(r) Office Excel 2003 SP
      1 (Excel (c) 1985-2003 Microsoft Corporation). Statistica Version 10 (copyright
      (c) Stat Soft, Inc. 1984-2011) was used to calculate the descriptive statistics.
      RESULTS: The main finding of the study was that nearly 70% of the respondents who
      purchased supplements were strongly influenced by container label information
      that stipulated that the nutritional supplement product is free of banned
      substances. The second finding was that just over 50% of the respondents attached
      importance to the quality of the nutritional supplement product information on
      the container label. The third finding was that about 40% of the respondents were
      strongly influenced by the ingredients on the labels when they purchased
      nutritional supplements. CONCLUSION: This study, (i) identifies short-comings in
      current labelling information practices, (ii) provides opportunities to improve
      label and non-label information and communication, and, (iii) presents the case
      for quality assurance laboratory "screening testing" of declared and undeclared
      contaminants and/or adulterants, that could have negative consequences to the
      consumer.

PMID- 24088194
TI  - Utility and limitations of Spa-typing in understanding the epidemiology of
      Staphylococcus aureus bacteraemia isolates in a single University Hospital.
AB  - BACKGROUND: Staphylococcus aureus (SA) is a recognized cause of nosocomial
      infections with 8,767 SA bacteraemia (SAB) cases reported in England only in
      2012. Different typing methods have been developed but they are not generally
      performed as a routine investigation in hospital laboratories. FINDINGS: We
      collected epidemiological data and spa-typed all SAB isolates over a 12 months
      period. Spa-typing was useful to detect two potential outbreaks of methicillin
      sensitive SA (MSSA). In addition, the analysis of spa-types from individuals with
      multiple bacteriaemias helped to distinguish between relapse and re-infection.
      CONCLUSIONS: Spa-typing could be used as a rapid tool to understand the
      epidemiology of SAB, in particular the detection of hospital clusters and to
      distinguish relapse from re-infection, but clinicians should be aware of its
      possible limitations.

PMID- 24088195
TI  - Symptom severity and psychological sequelae in rosacea: results of a survey.
AB  - Rosacea is associated with mental distress and depression, yet no studies have
      looked at the mediating effect of stigmatization and other factors on
      psychological sequelae. Using a survey of affected individuals, the objective of
      this study was to explore relationships between self-reported symptom severity,
      discomfort, stress reactivity, quality of life, and symptoms of depression and
      anxiety. Participants were recruited from the mailing list of a German rosacea
      organization. The survey instrument included the Dermatology Life Quality Index
      (DLQI), the rejection scale of the Questionnaire on Experience with Skin
      Complaints (QES), and the German version of the Hospital Anxiety and Depression
      Scale (HADS-D). A total of 168 persons with rosacea were participated. The sample
      returned a HADS anxiety score of 7.2 +/- 4.60, a HADS depression score of 5.1 +/-
      4.09, a DLQI of 4.05 +/- 4.67, and a QES rejection score of 2.,61 +/- 3.,37. Path
      analysis suggested that symptoms of anxiety and depression are linked with
      somatic symptoms indirectly, mediated through quality of life and stigmatization.
      Men are more negatively affected. Physicians treating rosacea patients should
      consider recommending psychological co-treatment for patients who have
      experienced stigmatization or who report low life quality.

PMID- 24088196
TI  - Early infant diagnosis of HIV in three regions in Tanzania; successes and
      challenges.
AB  - BACKGROUND: By the end of 2009 an estimated 2.5 million children worldwide were
      living with HIV-1, mostly as a consequence of vertical transmission, and more
      than 90% of these children live in sub-Saharan Africa. In 2008 the World Health
      Organization (WHO), recommended early initiation of Highly Active Antiretroviral
      Therapy (HAART) to all HIV infected infants diagnosed within the first year of
      life, and since 2010, within the first two years of life, irrespective of CD4
      count or WHO clinical stage. The study aims were to describe implementation of
      EID programs in three Tanzanian regions with differences in HIV prevalences and
      logistical set-up with regard to HIV DNA testing. METHODS: Data were obtained by
      review of the prevention from mother to child transmission of HIV (PMTCT)
      registers from 2009-2011 at the Reproductive and Child Health Clinics (RCH) and
      from the databases from the Care and Treatment Clinics (CTC) in all the three
      regions; Kilimanjaro, Mbeya and Tanga. Statistical tests used were Poisson
      regression model and rank sum test. RESULTS: During the period of 2009 - 2011 a
      total of 4,860 exposed infants were registered from the reviewed sites, of whom
      4,292 (88.3%) were screened for HIV infection. Overall proportion of tested
      infants in the three regions increased from 77.2% in 2009 to 97.8% in 2011. A
      total of 452 (10.5%) were found to be HIV infected (judged by the result of the
      first test). The prevalence of HIV infection among infants was higher in Mbeya
      when compared to Kilimanjaro region RR = 1.872 (95%CI = 1.408 - 2.543) p < 0.001.
      However sample turnaround time was significantly shorter in both Mbeya (2.7
      weeks) and Tanga (5.0 weeks) as compared to Kilimanjaro (7.0 weeks), p=<0.001. A
      substantial of loss to follow-up (LTFU) was evident at all stages of EID services
      in the period of 2009 to 2011. Among the infants who were receiving treatment,
      61% were found to be LFTU during the review period. CONCLUSION: The study showed
      an increase in testing of HIV exposed infants within the three years, there is
      large variations of HIV prevalence among the regions. Challenges like; sample
      turnaround time and LTFU must be overcome before this can translate into the
      intended goal of early initiation of lifelong lifesaving antiretroviral therapy
      for the infants.

PMID- 24088198
TI  - Estimating the size of the MSM populations for 38 European countries by
      calculating the survey-surveillance discrepancies (SSD) between self-reported new
      HIV diagnoses from the European MSM internet survey (EMIS) and surveillance
      reported HIV diagnoses among MSM in 2009.
AB  - BACKGROUND: Comparison of rates of newly diagnosed HIV infections among MSM
      across countries is challenging for a variety of reasons, including the unknown
      size of MSM populations. In this paper we propose a method of triangulating
      surveillance data with data collected in a pan-European MSM Internet Survey
      (EMIS) to estimate the sizes of the national MSM populations and the rates at
      which HIV is being diagnosed amongst them by calculating survey-surveillance
      discrepancies (SSD) as a measure of selection biases of survey participants.
      METHODS: In 2010, the first EMIS collected self-reported data on HIV diagnoses
      among more than 180,000 MSM in 38 countries of Europe. These data were compared
      with data from national HIV surveillance systems to explore possible sampling and
      reporting biases in the two approaches. The Survey-Surveillance Discrepancy (SSD)
      represents the ratio of survey members diagnosed in 2009 (HIVsvy) to total survey
      members (Nsvy), divided by the ratio of surveillance reports of diagnoses in 2009
      (HIVpop) to the estimated total MSM population (Npop). As differences in
      household internet access may be a key component of survey selection biases, we
      analysed the relationship between household internet access and SSD in countries
      conducting consecutive MSM internet surveys at different time points with
      increasing levels of internet access. The empirically defined SSD was used to
      calculate the respective MSM population sizes (Npop), using the formula Npop =
      HIVpop*Nsvy*SSD/HIVsvy. RESULTS: Survey-surveillance discrepancies for
      consecutive MSM internet surveys between 2003 and 2010 with different levels of
      household internet access were best described by a potential equation, with high
      SSD at low internet access, declining to a level around 2 with broad access. The
      lowest SSD was calculated for the Netherlands with 1.8, the highest for Moldova
      with 9.0. Taking the best available estimate for surveillance reports of HIV
      diagnoses among MSM in 2009 (HIVpop), the relative MSM population sizes were
      between 0.03% and 5.6% of the adult male population aged 15-64. The correlation
      between recently diagnosed (2009) HIV in EMIS participants and HIV diagnosed
      among MSM in 2009 as reported in the national surveillance systems was very high
      (R(2) = 0.88) when using the calculated MSM population size. CONCLUSIONS: Npop
      and HIVpop were unreliably low for several countries. We discuss and identify
      possible measurement errors for countries with calculated MSM population sizes
      above 3% and below 1% of the adult male population. In most cases the number of
      new HIV diagnoses in MSM in the surveillance system appears too low. In some
      cases, measurement errors may be due to small EMIS sample sizes. It must be
      assumed that the SSD is modified by country-specific factors.Comparison of
      community-based survey data with surveillance data suggests only minor sampling
      biases in the former that--except for a few countries--do not seriously distort
      inter-country comparability, despite large variations in participation rates
      across countries. Internet surveys are useful complements to national
      surveillance systems, highlighting deficiencies and allowing estimates of the
      range of newly diagnosed infections among MSM in countries where surveillance
      systems fail to accurately provide such data.

PMID- 24088199
TI  - Statistical analysis of dendritic spine distributions in rat hippocampal
      cultures.
AB  - BACKGROUND: Dendritic spines serve as key computational structures in brain
      plasticity. Much remains to be learned about their spatial and temporal
      distribution among neurons. Our aim in this study was to perform exploratory
      analyses based on the population distributions of dendritic spines with regard to
      their morphological characteristics and period of growth in dissociated
      hippocampal neurons. We fit a log-linear model to the contingency table of spine
      features such as spine type and distance from the soma to first determine which
      features were important in modeling the spines, as well as the relationships
      between such features. A multinomial logistic regression was then used to predict
      the spine types using the features suggested by the log-linear model, along with
      neighboring spine information. Finally, an important variant of Ripley's K
      function applicable to linear networks was used to study the spatial distribution
      of spines along dendrites. RESULTS: Our study indicated that in the culture
      system, (i) dendritic spine densities were "completely spatially random", (ii)
      spine type and distance from the soma were independent quantities, and most
      importantly, (iii) spines had a tendency to cluster with other spines of the same
      type. CONCLUSIONS: Although these results may vary with other systems, our
      primary contribution is the set of statistical tools for morphological modeling
      of spines which can be used to assess neuronal cultures following gene
      manipulation such as RNAi, and to study induced pluripotent stem cells
      differentiated to neurons.

PMID- 24088200
TI  - Central venous catheter placement in children: 'how good is good enough?'.

PMID- 24088201
TI  - Upper body central venous catheters in pediatric cardiac surgery.
AB  - BACKGROUND: A central venous catheter located in the jugular or subclavian vein
      provides rapid, reliable vascular access for pediatric heart surgery. However,
      intravascular catheters are associated with vessel injury. Stenosis or thrombosis
      of central veins in the upper body can lead to 'superior vena cava syndrome' with
      markedly elevated venous pressures in the head and neck, causing facial swelling
      and headaches. This complication may be especially serious for patients with
      superior cavopulmonary (Glenn) or total cavopulmonary (Fontan) circulation. The
      authors hypothesized that upper body central line placement would be associated
      with a low risk of venous thrombosis or stenosis. METHODS: A three-year
      retrospective review of infant and univentricular cardiac procedures at a single
      institution was performed. Two hundred and thirty-five consecutive cardiac
      surgical patients <1 year of age or undergoing palliation for univentricular
      cardiac anatomy up to five years of age during January 2010 to December 2012 were
      included in this study. Upper body central lines are routinely placed by the
      anesthesiologist after induction of anesthesia for pediatric cardiac surgery at
      the study institution. The major exception is existing central venous access via
      an umbilical vein or femoral vein. Patients <2 years of age received a 4.0
      French, 5-cm double-lumen central line [Cook Medical polyurethane, no antibiotic
      or heparin coating]. Those over two years of age received a 5.0-French, 8-cm
      triple lumen central line [Cook Medical polyurethane, no antibiotic or heparin
      coating]. A retrospective review of charts, hospital reports, echocardiographic
      studies, and cardiac catheterization studies was performed. RESULTS: The combined
      population of infants <1 year of age and patients <5 years of age with functional
      univentricular hearts totaled 235 patients who underwent 261 cardiac surgical
      operations. In this cohort of 261 cases, 171 size 4.0 or 5.0-French upper body
      central lines were inserted. A total of 158 right internal jugular vein catheters
      were placed. Two left internal jugular lines, two left subclavian lines, and nine
      right subclavian lines were placed in this population after failure to obtain
      right internal jugular access. Due to the small sample size (N = 13), the central
      lines not placed in the right internal jugular vein were excluded from further
      review. Two cases with right internal jugular venous lines were excluded due to
      death (without known stenosis or thrombosis) with the line in place. Twenty-three
      size 4.0- or 5.0-French right internal jugular central venous lines were placed
      in patients over one year of age (range 1.1-4.3 years) having modified Glenn- or
      Fontan-type surgery. The central lines were removed with a median of 1.4 days
      after insertion (range 0.7-8.2 days) for these older children, compared with a
      median of 4.2 days of age (range 0.3-19.3 days) for the 133 children <1 year of
      age. Retrospective chart review of nursing notes, progress notes, cardiology
      notes, discharge summaries, echocardiographic reports, and cardiac
      catheterization reports for all patients who received an upper body central
      venous line (internal jugular or subclavian) showed no definitive diagnosis of an
      upper body venous stenosis or thrombosis related to the central venous line. A
      further targeted review of echocardiographic and cardiac catheterization studies
      for univentricular cardiac patients failed to show stenosis or thrombosis of a
      vessel associated with upper body central line placement. CONCLUSIONS: This study
      describes one institution's experience with routine upper body central venous
      catheter placement for neonatal and infant cardiac surgery as well as
      univentricular cardiac palliation (Glenn and Fontan procedures) with minimal risk
      of clinically significant catheter-associated vessel thrombosis or stenosis. No
      upper body central venous stenosis or thrombosis was detected in association with
      perioperative catheter placement in the upper body central venous system,
      primarily the right internal jugular vein in 156 cases. Right internal jugular
      central line placement for infant cardiac surgery can be utilized with a low risk
      of direct venous thrombosis or stenosis.

PMID- 24088202
TI  - Sickle cell pain management: are we missing the role of pronociception and
      neuropathic pain?

PMID- 24088203
TI  - Postoperative cerebral arterial thrombosis following cranial surgery in an
      infant.

PMID- 24088204
TI  - Unilateral spinal anesthesia in a pediatric patient with Duchenne muscular
      dystrophy: a case report.

PMID- 24088197
TI  - A comprehensive map of the influenza A virus replication cycle.
AB  - BACKGROUND: Influenza is a common infectious disease caused by influenza viruses.
      Annual epidemics cause severe illnesses, deaths, and economic loss around the
      world. To better defend against influenza viral infection, it is essential to
      understand its mechanisms and associated host responses. Many studies have been
      conducted to elucidate these mechanisms, however, the overall picture remains
      incompletely understood. A systematic understanding of influenza viral infection
      in host cells is needed to facilitate the identification of influential host
      response mechanisms and potential drug targets. DESCRIPTION: We constructed a
      comprehensive map of the influenza A virus ('IAV') life cycle ('FluMap') by
      undertaking a literature-based, manual curation approach. Based on information
      obtained from publicly available pathway databases, updated with literature-based
      information and input from expert virologists and immunologists, FluMap is
      currently composed of 960 factors (i.e., proteins, mRNAs etc.) and 456 reactions,
      and is annotated with ~500 papers and curation comments. In addition to detailing
      the type of molecular interactions, isolate/strain specific data are also
      available. The FluMap was built with the pathway editor CellDesigner in standard
      SBML (Systems Biology Markup Language) format and visualized as an SBGN (Systems
      Biology Graphical Notation) diagram. It is also available as a web service
      (online map) based on the iPathways+ system to enable community discussion by
      influenza researchers. We also demonstrate computational network analyses to
      identify targets using the FluMap. CONCLUSION: The FluMap is a comprehensive
      pathway map that can serve as a graphically presented knowledge-base and as a
      platform to analyze functional interactions between IAV and host factors.
      Publicly available webtools will allow continuous updating to ensure the most
      reliable representation of the host-virus interaction network. The FluMap is
      available at http://www.influenza-x.org/flumap/.

PMID- 24088205
TI  - Microbial community changes in hydraulic fracturing fluids and produced water
      from shale gas extraction.
AB  - Microbial communities associated with produced water from hydraulic fracturing
      are not well understood, and their deleterious activity can lead to significant
      increases in production costs and adverse environmental impacts. In this study,
      we compared the microbial ecology in prefracturing fluids (fracturing source
      water and fracturing fluid) and produced water at multiple time points from a
      natural gas well in southwestern Pennsylvania using 16S rRNA gene-based clone
      libraries, pyrosequencing, and quantitative PCR. The majority of the bacterial
      community in prefracturing fluids constituted aerobic species affiliated with the
      class Alphaproteobacteria. However, their relative abundance decreased in
      produced water with an increase in halotolerant, anaerobic/facultative anaerobic
      species affiliated with the classes Clostridia, Bacilli, Gammaproteobacteria,
      Epsilonproteobacteria, Bacteroidia, and Fusobacteria. Produced water collected at
      the last time point (day 187) consisted almost entirely of sequences similar to
      Clostridia and showed a decrease in bacterial abundance by 3 orders of magnitude
      compared to the prefracturing fluids and produced water samplesfrom earlier time
      points. Geochemical analysis showed that produced water contained higher
      concentrations of salts and total radioactivity compared to prefracturing fluids.
      This study provides evidence of long-term subsurface selection of the microbial
      community introduced through hydraulic fracturing, which may include significant
      implications for disinfection as well as reuse of produced water in future
      fracturing operations. 

PMID- 24088207
TI  - Economic transformation in health care: implications for rural communities.

PMID- 24088206
TI  - New aspects on efficient anticoagulation and antiplatelet strategies in sheep.
AB  - BACKGROUND: After addressing fundamental questions in preclinical models in vitro
      or in small animals in vivo, the translation into large animal models has become
      a prerequisite before transferring new findings to human medicine. Especially in
      cardiovascular, orthopaedic and reconstructive surgery, the sheep is an important
      in vivo model for testing innovative therapies or medical devices prior to
      clinical application. For a wide variety of sheep model based research projects,
      an optimal anticoagulation and antiplatelet therapy is mandatory. However, no
      standardised scheme for this model has been developed so far. Thus the efficacy
      of antiplatelet (acetylsalicylic acid, clopidogrel, ticagrelor) and anticoagulant
      (sodium enoxaparin, dabigatran etexilate) strategies was evaluated through
      aggregometry, anti-factor Xa activity and plasma thrombin inhibitor levels in
      sheep of different ages. RESULTS: Responses to antiplatelet and anticoagulant
      drugs in different concentrations were studied in the sheep. First, a baseline
      for the measurement of platelet aggregation was assessed in 20 sheep. The
      effectiveness of 225 mg clopidogrel twice daily (bid) in 2/5 sheep and 150 mg bid
      in 3/5 lambs could be demonstrated, while clopidogrel and its metabolite
      carboxylic acid were detected in every plasma sample. High dose ticagrelor (375
      mg bid) resulted in sufficient inhibition of platelet aggregation in 1/5 sheep,
      while acetylsalicylic acid did not show any antiplatelet effect. Therapeutic anti
      factor Xa levels were achieved with age-dependent dosages of sodium enoxaparin
      (sheep 3 mg/kg bid, lambs 5 mg/kg bid). Administration of dabigatran etexilate
      resulted in plasma concentrations similar to human ranges in 2/5 sheep, despite
      receiving quadruple dosages (600 mg bid). CONCLUSION: High dosages of clopidogrel
      inhibited platelet aggregation merely in a low number of sheep despite sufficient
      absorption. Ticagrelor and acetylsalicylic acid cannot be recommended for
      platelet inhibition in sheep. Efficient anticoagulation can be ensured using
      sodium enoxaparin rather than dabigatran etexilate in age-dependent dosages. The
      findings of this study significantly contribute to the improvement of a safe and
      reliable prophylaxis for thromboembolic events in sheep. Applying these results
      in future translational experimental studies may help to avoid early dropouts due
      to thromboembolic events and associated unnecessary high animal numbers.

PMID- 24088208
TI  - Geographic disparities in patient travel for dialysis in the United States.
AB  - PURPOSE: To estimate travel distance and time for US hemodialysis patients and to
      compare travel of rural versus urban patients. METHODS: Dialysis patient
      residences were estimated from ZIP code-level patient counts as of February 2011
      allocated within the ZIP code proportional to census tract-level population,
      obtained from the 2010 U.S. Census. Dialysis facility addresses were obtained
      from Medicare public-use files. Patients were assigned to an "original" and
      "replacement" facility, assuming patients used the facility closest to home and
      would select the next closest facility as a replacement, if a replacement
      facility was required. Driving distances and times were calculated between
      patient residences and facility locations using GIS software. FINDINGS: The mean
      one-way driving distance to the original facility was 7.9 miles; for rural
      patients average distances were 2.5 times farther than for urban patients (15.9
      vs. 6.2 miles). Mean driving distance to a replacement facility was 10.6 miles,
      with rural patients traveling on average 4 times farther than urban patients to a
      replacement facility (28.8 vs. 6.8 miles). CONCLUSION: Rural patients travel much
      longer distances for dialysis than urban patients. Accessing alternative
      facilities, if required, would greatly increase rural patient travel, while
      having little impact on urban patients. Increased travel could have clinical
      implications as longer travel is associated with increased mortality and
      decreased quality of life.

PMID- 24088209
TI  - Relationships between health behaviors and weight status in American Indian and
      white rural children.
AB  - PURPOSE: Preventing obesity in childhood is an increasingly important public
      health goal. Prevention efforts can be improved by better understanding
      relationships between health behaviors and overweight and obesity. This study
      examined such relationships in young American Indian and white children living in
      the rural United States. METHODS: Self-report measures of diet, screen time
      (passive and active), and physical activity were combined with cardiovascular
      fitness in cross-sectional analyses to predict weight categories based on body
      mass index percentiles in 306 American Indian and white children (aged 8-9 years)
      from a rural area in the upper Midwestern United States. FINDINGS: Multinomial
      logistic regression models were statistically significant for girls (chi2 [20] =
      42.73, P < .01), boys (chi2 [20] = 50.44, P < .001), American Indian (chi2 [20] =
      36.67, P < .05), and white children (chi2 [20] = 55.99, P < .001). Obesity was
      associated with poorer cardiovascular fitness in girls (OR = 0.82), boys (OR =
      0.83), American Indian (OR = 0.79), and white children (OR = 0.85), and with
      passive screen time in girls (OR = 1.69), boys (OR = 2.1), and white children (OR
      = 1.81). Overweight was associated with passive screen time (OR = 2.24) and
      inversely with active screen time (OR = 0.54), but only in boys. CONCLUSIONS:
      Logistic regression models were more successful at predicting obesity than
      overweight in all groups of participants. Poorer cardiovascular fitness showed
      the strongest and most consistent association with obesity, but passive screen
      time was also a significant and important contributor to the prediction of
      obesity in most prediction models. Prediction models were similar in girls, boys,
      American Indian, and white children.

PMID- 24088210
TI  - Increasing access to cholesterol screening in rural communities catalyzes
      cardiovascular disease prevention.
AB  - PURPOSE: Despite increasing frequency, little evidence guides cholesterol
      screening in less traditional health care settings, such as rural health fairs.
      METHODS: The Miller School of Medicine Department of Community Service (DOCS) is
      a student-run organization providing free basic health care to underserved South
      Florida communities. We retrospectively reviewed all new patients seen at 2007
      DOCS rural fairs to describe their low-density lipoprotein (LDL) and high-density
      lipoprotein (HDL) values. In addition, we assessed if patient characteristics
      were associated with cholesterol abnormalities and whether patients with
      abnormalities who returned to a subsequent fair in 2008 or 2009 improved their
      cholesterol. FINDINGS: Of 252 patients, 145 (58%) had an LDL cholesterol over 129
      mg/dL and 61 (24%) had an HDL cholesterol below 40 mg/dL or 50 mg/dL for males
      and females, respectively. Baseline LDL cholesterol was not associated with body
      mass index (BMI), age over 60 years, gender, healthy lifestyle habits, or
      insurance status. Of 36 patients with elevated LDL cholesterol and a follow-up
      screening, 24 (67%) reduced their LDL cholesterol by at least 16 mg/dL though
      reductions were not associated with BMI reduction, and 22 (61%) increased their
      HDL cholesterol by at least 5 mg/dL, trending with BMI reduction. CONCLUSIONS:
      Cholesterol screening at rural fairs can identify a high proportion of patients
      with abnormal cholesterol, including those who might not be considered at high
      risk. Although this may catalyze favorable cholesterol changes, the lack of an
      association with weight loss suggests patients seek additional medical care,
      which should be considered before offering cholesterol screening at fairs.

PMID- 24088211
TI  - "Living with a ball and chain": the experience of stroke for individuals and
      their caregivers in rural Appalachian Kentucky.
AB  - PURPOSE: Individuals in rural Appalachian Kentucky face health disparities and
      are at increased risk for negative health outcomes and poor quality of life
      secondary to stroke. The purpose of this study is to describe the experience of
      stroke for survivors and their caregivers in this region. A description of their
      experiences is paramount to developing tailored interventions and ultimately
      improving health care and support. METHODS: An interprofessional research team
      used a qualitative descriptive study design and interviewed 13 individuals with
      stroke and 12 caregivers, representing 10 rural Appalachian Kentucky counties.
      The transcripts were analyzed using qualitative content analysis. FINDINGS: A
      descriptive summary of the participants' experience of stroke is presented within
      the following structure: (1) Stroke onset, (2) Transition through the health care
      continuum (including acute care, inpatient rehabilitation, and community-based
      rehabilitation), and (3) Reintegration into life and rural communities.
      CONCLUSIONS: The findings provide insight for rural health care providers and
      community leaders to begin to understand the experience of stroke in terms of
      stroke onset, transition through the health care continuum, return to home, and
      community reintegration. An understanding of these experiences may lead to
      discussions of how to improve service provision, facilitate reintegration,
      support positive health outcomes, and improve quality of life for stroke
      survivors and their caregivers. The findings also indicate areas in need of
      future research including investigation of the effects of support groups, local
      health navigators to improve access to information and services, involvement of
      faith communities, proactive screening for management of mental health needs, and
      caregiver respite services.

PMID- 24088212
TI  - Patient safety perspectives of providers and nurses: the experience of a rural
      ambulatory care practice using an EHR with E-prescribing.
AB  - PURPOSE: The purpose of this study was to identify and describe safety
      improvements and concerns indicated by providers and nurses in a rural community
      ambulatory care practice using an electronic health record with an e-prescribing
      feature (EHR with eRx). METHODS: Two focus groups were conducted; 1 with
      providers and the other with nurses. Participants responded to questions and
      discussed their perceptions of safety improvements and concerns with use of an
      EHR with eRx. Transcripts were analyzed using sequential and continuous analytic
      methods. FINDINGS: Three themes centered on efficiency and patient safety emerged
      from data analysis: (1) EHR with eRx adoption has led to new improvements and
      concerns for patient safety, (2) the EHR with eRx has affected efficiency in the
      clinic, and (3) EHR with eRx adoption has led to workarounds. CONCLUSIONS:
      Concerns remain among providers and nurses regarding the use of EHR with eRx
      applications, although concerns differed between groups. Therefore, When EHR
      improvements are planned, it is important to consider the differing needs of the
      professionals who deliver care.

PMID- 24088213
TI  - Health literacy and urbanicity among cancer patients.
AB  - PURPOSE: Low health literacy is associated with inadequate health care
      utilization and poor health outcomes, particularly among elderly persons. There
      is a dearth of research exploring the relationship between health literacy and
      place of residence (urbanicity). This study examined the association between
      urbanicity and health literacy, as well as factors related to low health
      literacy, among cancer patients. METHODS: A cross-sectional survey was conducted
      with a population-based sample of 1,841 cancer patients in Wisconsin. Data on
      sociodemographics, urbanicity, clinical characteristics, insurance status, and
      health literacy were obtained from the state's cancer registry and participants'
      answers to a mailed questionnaire. Partially and fully adjusted multivariate
      logistic regression models were fitted to examine: (1) the association between
      urbanicity and health literacy and (2) the role of socioeconomic status as a
      possible mediator of this relationship. FINDINGS: Rural cancer patients had a 33%
      (95% CI: 1.06-1.67) higher odds of having lower levels of health literacy than
      their counterparts in more urban areas of Wisconsin. The association between
      urbanicity and health literacy attenuated after controlling for socioeconomic
      status. CONCLUSIONS: Level of urbanicity was significantly related to health
      literacy. Socioeconomic status fully mediated the relationship between urbanicity
      and health literacy. These results call for policies and interventions to assess
      and address health literacy barriers among cancer patients in rural areas.

PMID- 24088214
TI  - Prevalence of and factors associated with subclinical posttraumatic stress
      symptoms and PTSD in urban and rural areas of Montana: a cross-sectional study.
AB  - PURPOSE: Posttraumatic stress disorder (PTSD) is an important clinical problem,
      but little is known about PTSD in rural, nonclinical populations. To better
      understand PTSD in rural areas, we examined the prevalence and risk and
      protective factors in urban, rural, and highly rural communities in Montana for
      both subclinical posttraumatic stress symptoms (PTSS) and PTSD. METHODS: We
      compared the prevalence of PTSS and PTSD in urban, rural, and highly rural
      communities in bivariate and multivariable regression analyses using self
      reported cross-sectional survey data from the Montana Health Matters study (N =
      3,512), a state-representative household-based survey done in 2010-2011. We also
      explore potential risk and protective factors for PTSS and PTSD and whether risk
      and protective factors for each differ by rurality. FINDINGS: There were no
      differences in the level of PTSS by rurality in bivariate or multivariate models,
      and the bivariate relationship between rurality and PTSD became nonsignificant in
      a multivariate model. Only locus of control was predictive for PTSS; however,
      gender, age, marital status, income, employment status, community fit, locus of
      control, and religiosity were associated with PTSD. Some risk and protective
      factors operate differently by rurality. CONCLUSIONS: Although our findings are
      subject to weaknesses common to cross-sectional data and are based on
      questionnaire reports, it appears that there are different risk and protective
      factors for PTSS and PTSD, suggesting that PTSD may be qualitatively different
      from PTSS. Furthermore, differences in risk and protective factors across urban
      and rural communities suggest more attention is needed to understand PTSD in
      rural communities.

PMID- 24088215
TI  - Communication and mass vaccination strategies after pertussis outbreak in rural
      Amish communities-Illinois, 2009-2010.
AB  - PURPOSE: During January 2010, 2 infants from an Amish community in east-central
      Illinois were hospitalized with pertussis. The local health department (LDH)
      intervened to control disease transmission, identify contributing factors, and
      determine best communications methods to improve vaccination coverage. METHODS: A
      retrospective cohort study was conducted using public health surveillance data to
      determine the extent of the outbreak; the standard Centers for Disease Control
      and Prevention and Council of State and Territorial Epidemiologists case
      definition for pertussis was used. The standardized Illinois Department of Public
      Health pertussis patient interview form was used to collect demographic, symptom,
      vaccination history, and treatment history information. To control disease
      transmission, LDH staff worked with the Amish community to promote a vaccination
      campaign during February 6-April 30, 2010. FINDINGS: Forty-seven cases were
      identified, with onsets during December 2009-March 2010. Median age was 7
      (interquartile range 1-12) years. Nineteen (40%) patients were male; 39 (83%)
      were aged <18 years; 37 (79%) had not received any pertussis-containing vaccine.
      Presenting symptoms did not differ substantially between vaccinated and
      unvaccinated patients. Duration of cough was longer among unvaccinated than
      vaccinated patients (32 vs. 15.5 days, P = .002). Compared with vaccinated
      patients, proportionately more unvaccinated patients reported secondary household
      transmission (30% vs. 72%; P = .012). Through enhanced vaccination campaigns, 251
      (~10%) Amish community members were administered 254 pertussis-containing
      vaccines. CONCLUSIONS: Targeted health communication and outreach resulted in a
      successful vaccine campaign and long-running monthly vaccination clinic. Amish do
      not universally reject vaccines, and their practices regarding vaccination are
      not static.

PMID- 24088217
TI  - The precision study: examining the inter- and intra-assay variability of
      replicate measurements of BGStar, iBGStar and 12 other blood glucose monitors.
AB  - OBJECTIVE: Self-monitoring of blood glucose is a key element in diabetes
      management. Accurate and precise performance of blood glucose monitors (BGMs)
      ensures that valid values are obtained to guide treatment decisions by patients
      and physicians. BGStar and iBGStar are hand-held BGMs that use dynamic
      electrochemistry to correct for potential interferences and thereby minimize
      system errors. RESEARCH DESIGN AND METHODS: A single-center, in vitro diagnostic
      device performance evaluation with heparinized oxygenated venous blood samples
      (intra-assay precision) and control solutions (interassay precision) was
      performed in a laboratory setting, comparing BGStar and iBGStar with 12
      competitors. MAIN OUTCOME MEASURES: The primary outcome was the coefficient of
      variation percent (CV%) of the BGMs investigated. RESULTS: In inter-assay
      precision analyses, all but GlucoMen LX had a CV <5%, and in intra-assay
      precision analyses, 10 of the 14 devices tested had CV <5%. BGStar and iBGStar
      had a CV <5% in both the inter- and intra-assay precision analyses. The smallest
      variation was found in the near-normoglycemic glucose range (5.3 - 8.0 mmol/l)
      for both BGStar and iBGStar in the inter-assay precision analysis. CONCLUSIONS:
      BGStar and iBGStar were proven to have very good inter-assay and high intra-assay
      precision, demonstrating low scattering of replicate measurements with both
      clinical samples and control solutions.

PMID- 24088216
TI  - A qualitative analysis of provider barriers and solutions to HIV testing for
      substance users in a small, largely rural southern state.
AB  - PURPOSE: Integrating HIV testing programs into substance use treatment is a
      promising avenue to help increase access to HIV testing for rural drug users. Yet
      few outpatient substance abuse treatment facilities in the United States provide
      HIV testing. The purpose of this study was to identify barriers to incorporating
      HIV testing with substance use treatment from the perspectives of treatment and
      testing providers in Arkansas. METHODS: We used purposive sampling from state
      directories to recruit providers at state, organization, and individual levels to
      participate in this exploratory study. Using an interview guide, the first and
      second authors conducted semistructured individual interviews in each provider's
      office or by telephone. All interviews were recorded, transcribed verbatim, and
      entered into ATLAS.ti software (ATLAS.ti Scientific Software Development GmbH,
      Berlin, Germany). We used constant comparison and content analysis techniques to
      identify codes, categories, and primary patterns in the data. FINDINGS: The
      sample consisted of 28 providers throughout the state, 18 from the substance use
      system and 10 from the public/ community health system. We identified 7
      categories of barriers: environmental constraints, policy constraints, funding
      constraints, organizational structure, limited inter- and intra-agency
      communication, burden of responsibility, and client fragility. CONCLUSIONS: This
      study presents the practice-based realities of barriers to integrating HIV
      testing with substance use treatment in a small, largely rural state. Some system
      and/or organization leaders were either unaware of or not actively pursuing
      external funds available to them specifically for engaging substance users in HIV
      testing. However, funding does not address the system-level need for coordination
      of resources and services at the state level.

PMID- 24088218
TI  - Does Finnish hospital staff job satisfaction vary across occupational groups?
AB  - BACKGROUND: Job satisfaction of staff is an essential outcome variable in
      research when describing the work environment of successful hospitals. Numerous
      studies have evaluated the topic, but few previous studies have assessed the job
      satisfaction of all staff in hospital settings. It is important to discover if
      there are any unsatisfied groups of people working in hospitals, the aspects they
      are unsatisfied with and why. The aim of this study was to evaluate job
      satisfaction of all staff working at a Finnish university hospital, identify
      differences in job satisfaction between staff groups, and explore the
      relationship between their self-evaluated quality of work and job satisfaction.
      METHODS: Data were collected from 1424 employees of the hospital using the web
      based Kuopio University Job Satisfaction Scale survey instrument in autumn 2010.
      The research data were analysed by using SPSS 19.0 for Windows. Frequency and
      percentage distributions, as well as mean values, were used to describe the data.
      A non-parametric test (Kruskal-Wallis test) was used to determine the
      significance of differences in scores between different groups of staff members
      and between quality evaluations. RESULTS: The overall job satisfaction of the
      employees was good. They rated both motivating factors of their work and work
      welfare as excellent. The areas causing most dissatisfaction were work demands
      and participation in decision making. Physicians formed the most satisfied group,
      nurses and maintenance staff were the least satisfied, and office and
      administrative staff were fairly satisfied. Staff who rated the quality of work
      in their units as high usually also considered their job satisfaction to be
      excellent. CONCLUSIONS: Every staff member has an influence on job satisfaction
      in her/his unit. A culture of participation should be developed and maintained in
      the units and the whole hospital to ensure that all staff feel they play
      important roles in the hospital. A university hospital is a complex, continuously
      changing work environment. Managers of the hospital should continuously evaluate
      job satisfaction and quickly react to the results gained.

PMID- 24088219
TI  - Early changes in somatosensory function in spinal pain: protocol for a systematic
      review.
AB  - BACKGROUND: Back and neck pain are common conditions that have a high burden of
      disease. Changes in somatosensory function in the periphery, the spinal cord and
      the brain have been well documented at the time when these conditions have become
      chronic. It is unknown, however, how early these changes occur, what the
      timecourse is of sensory dysfunction and what the specific nature of these
      changes are in the first 12 weeks after onset of pain. In this paper, we describe
      the protocol for a systematic review of the literature on somatosensory
      dysfunction in the first 12 weeks after pain onset. METHODS AND DESIGN: We will
      conduct a comprehensive search for articles indexed in the databases Ovid
      MEDLINE, Ovid Embase, Ovid PsycINFO and Cochrane Central Register of Controlled
      Trial (CENTRAL) from their inception to August 2013 that report on any aspect of
      somatosensory function in acute or subacute neck or back pain. Two independent
      reviewers will screen studies for eligibility, assess risk of bias and extract
      relevant data. Results will be tabulated and a narrative synthesis of the results
      conducted. DISCUSSION: Currently, there is a gap in our knowledge about the
      timing of somatosensory changes in back and neck pain. The systematic review
      outlined in this protocol aims to address this knowledge gap and inform
      developments in diagnostic tools and pain mechanism-based treatments. TRIAL
      REGISTRATION: Our protocol has been registered on PROSPERO, CRD42013005113.

PMID- 24088220
TI  - Distributions of types I, II and III collagen by region in the human
      supraspinatus tendon.
AB  - The mechanical properties of the human supraspinatus tendon (SST) are highly
      heterogeneous and may reflect an important adaptive response to its complex,
      multiaxial loading environment. However, these functional properties are
      associated with a location-dependent structure and composition that have not been
      fully elucidated. Therefore, the objective of this study was to determine the
      concentrations of types I, II and III collagen in six distinct regions of the SST
      and compare changes in collagen concentration across regions with local changes
      in mechanical properties. We hypothesized that type I collagen content would be
      high throughout the tendon, type II collagen would be restricted to regions of
      compressive loading and type III collagen content would be high in regions
      associated with damage. We further hypothesized that regions of high type III
      collagen content would correspond to regions with low tensile modulus and a low
      degree of collagen alignment. Although type III collagen content was not
      significantly higher in regions that are frequently damaged, all other hypotheses
      were supported by our results. In particular, type II collagen content was
      highest near the insertion while type III collagen was inversely correlated with
      tendon modulus and collagen alignment. The measured increase in type II collagen
      under the coracoacromial arch provides evidence of adaptation to compressive
      loading in the SST. Moreover, the structure-function relationship between type
      III collagen content and tendon mechanics established in this study demonstrates
      a mechanism for altered mechanical properties in pathological tendons and
      provides a guideline for identifying therapeutic targets and pathology-specific
      biomarkers.

PMID- 24088221
TI  - An objective function exploiting suboptimal solutions in metabolic networks.
AB  - BACKGROUND: Flux Balance Analysis is a theoretically elegant, computationally
      efficient, genome-scale approach to predicting biochemical reaction fluxes. Yet
      FBA models exhibit persistent mathematical degeneracy that generally limits their
      predictive power. RESULTS: We propose a novel objective function for cellular
      metabolism that accounts for and exploits degeneracy in the metabolic network to
      improve flux predictions. In our model, regulation drives metabolism toward a
      region of flux space that allows nearly optimal growth. Metabolic mutants deviate
      minimally from this region, a function represented mathematically as a convex
      cone. Near-optimal flux configurations within this region are considered equally
      plausible and not subject to further optimizing regulation. Consistent with
      relaxed regulation near optimality, we find that the size of the near-optimal
      region predicts flux variability under experimental perturbation. CONCLUSION:
      Accounting for suboptimal solutions can improve the predictive power of metabolic
      FBA models. Because fluctuations of enzyme and metabolite levels are inevitable,
      tolerance for suboptimality may support a functionally robust metabolic network.

PMID- 24088224
TI  - Surface plasmon resonance of Au-Cu bimetallic nanoparticles predicted by a quasi
      chemical model.
AB  - Au-Cu alloys are functional materials with nonlinear optical applications.
      However, the optical properties of such alloys are difficult to predict due to
      the random mixing of materials. In this paper, we present a quasi-chemical model
      to simulate the optical properties of Au-Cu alloy systems based on the mixing of
      Gibbs free energy. This model is also able to predict the position of the surface
      plasmon resonance peaks for Au-Cu alloy nanoparticles. The model can be applied
      to predict the optical properties of alloy systems in the fields of plasmonics
      and nanophotonics. 

PMID- 24088225
TI  - Lovastatin improves impaired synaptic plasticity and phasic alertness in patients
      with neurofibromatosis type 1.
AB  - BACKGROUND: Neurofibromatosis type 1 (NF1) is one of the most common genetic
      disorders causing learning disabilities by mutations in the neurofibromin gene,
      an important inhibitor of the RAS pathway. In a mouse model of NF1, a loss of
      function mutation of the neurofibromin gene resulted in increased gamma
      aminobutyric acid (GABA)-mediated inhibition which led to decreased synaptic
      plasticity and deficits in attentional performance. Most importantly, these
      defictis were normalized by lovastatin. This placebo-controlled, double blind,
      randomized study aimed to investigate synaptic plasticity and cognition in humans
      with NF1 and tried to answer the question whether potential deficits may be
      rescued by lovastatin. METHODS: In NF1 patients (n = 11; 19-44 years) and healthy
      controls (HC; n = 11; 19-31 years) paired pulse transcranial magnetic stimulation
      (TMS) was used to study intracortical inhibition (paired pulse) and synaptic
      plasticity (paired associative stimulation). On behavioural level the Test of
      Attentional Performance (TAP) was used. To study the effect of 200 mg lovastatin
      for 4 days on all these parameters, a placebo-controlled, double blind,
      randomized trial was performed. RESULTS: In patients with NF1, lovastatin
      revealed significant decrease of intracortical inhibition, significant increase
      of synaptic plasticity as well as significant increase of phasic alertness.
      Compared to HC, patients with NF1 exposed increased intracortical inhibition,
      impaired synaptic plasticity and deficits in phasic alertness. CONCLUSIONS: This
      study demonstrates, for the first time, a link between a pathological RAS pathway
      activity, intracortical inhibition and impaired synaptic plasticity and its
      rescue by lovastatin in humans. Our findings revealed mechanisms of attention
      disorders in humans with NF1 and support the idea of a potential clinical benefit
      of lovastatin as a therapeutic option.

PMID- 24088226
TI  - Association of CYP2D6 metabolizer status with mammographic density change in
      response to tamoxifen treatment.
AB  - INTRODUCTION: Not all breast cancer patients respond to tamoxifen treatment,
      possibly due to genetic predisposition. As tamoxifen-induced reductions in
      percent mammographic density (PMD) have been linked to the risk and prognosis of
      breast cancer, we conducted a candidate gene study to investigate the association
      between germline CYP2D6 polymorphisms and PMD change. METHODS: Baseline and
      follow-up mammograms were retrieved for 278 tamoxifen-treated subjects with
      CYP2D6 metabolizer status (extensive (EM), heterozygous extensive/intermediate
      (hetEM/IM) or poor metabolizer (PM)). Logistic regression analyses were conducted
      comparing subjects who experienced >10% reduction in PMD to those who experienced
      <=10% reduction or increase. RESULTS: After multivariate adjustment, PMD change
      was found to be significantly associated with the degree of CYP2D6 enzyme
      functionality (Ptrend = 0.021). Compared with EM, hetEM/IM and PM were 72% (95%
      confidence interval (CI): 0.10 to 0.79) and 71% (0.03 to 2.62) less likely to
      experience a >10% reduction, respectively. CONCLUSIONS: Tamoxifen-induced change
      in PMD appears to have a genetic component.

PMID- 24088227
TI  - Changing trends in the treatment of dry-eye disease.
AB  - INTRODUCTION: Dry eye is a visually disabling disease encountered in many
      countries with a wide variation of treatment practices all over the world. On
      that front, the 2007 Report of the International Dry Eye WorkShop (DEWS) reviewed
      the current knowledge on all aspects of dry-eye disease (DED), in an evidence
      based manner, and outlined the trends and recommendations in the treatment of DED
      on the basis of disease severity. AREAS COVERED: This review mainly focuses on
      treatments for DED based on severity as recommended in the DEWS report,
      particularly artificial eye drops, hyaluronate sodium eye drops, autologous
      serum, anti-inflammatory eye drops including cyclosporine and steroids, and mucin
      secretagogues. New dry-eye treatment modalities in current trials outlined on the
      clinicaltrial.gov site are also outlined. EXPERT OPINION: Further investigations
      into the mechanism of action of the new mucin and tear secretagogues which have
      been suggested to have anti-inflammatory properties will enrich our understanding
      in relation to relevant ocular surface responses after treatment with these new
      agents.

PMID- 24088228
TI  - The dynamic sustainability framework: addressing the paradox of sustainment amid
      ongoing change.
AB  - BACKGROUND: Despite growth in implementation research, limited scientific
      attention has focused on understanding and improving sustainability of health
      interventions. Models of sustainability have been evolving to reflect challenges
      in the fit between intervention and context. DISCUSSION: We examine the
      development of concepts of sustainability, and respond to two frequent
      assumptions -'voltage drop,' whereby interventions are expected to yield lower
      benefits as they move from efficacy to effectiveness to implementation and
      sustainability, and 'program drift,' whereby deviation from manualized protocols
      is assumed to decrease benefit. We posit that these assumptions limit
      opportunities to improve care, and instead argue for understanding the changing
      context of healthcare to continuously refine and improve interventions as they
      are sustained. Sustainability has evolved from being considered as the endgame of
      a translational research process to a suggested 'adaptation phase' that
      integrates and institutionalizes interventions within local organizational and
      cultural contexts. These recent approaches locate sustainability in the
      implementation phase of knowledge transfer, but still do not address intervention
      improvement as a central theme. We propose a Dynamic Sustainability Framework
      that involves: continued learning and problem solving, ongoing adaptation of
      interventions with a primary focus on fit between interventions and multi-level
      contexts, and expectations for ongoing improvement as opposed to diminishing
      outcomes over time. SUMMARY: A Dynamic Sustainability Framework provides a
      foundation for research, policy and practice that supports development and
      testing of falsifiable hypotheses and continued learning to advance the
      implementation, transportability and impact of health services research.

PMID- 24088229
TI  - Transportation noise and annoyance related to road traffic in the French RECORD
      study.
AB  - Road traffic and related noise is a major source of annoyance and impairment to
      health in urban areas. Many areas exposed to road traffic noise are also exposed
      to rail and air traffic noise. The resulting annoyance may depend on
      individual/neighborhood socio-demographic factors. Nevertheless, few studies have
      taken into account the confounding or modifying factors in the relationship
      between transportation noise and annoyance due to road traffic. In this study, we
      address these issues by combining Geographic Information Systems and
      epidemiologic methods. Street network buffers with a radius of 500 m were defined
      around the place of residence of the 7290 participants of the RECORD Cohort in
      Ile-de-France. Estimated outdoor traffic noise levels (road, rail, and air
      separately) were assessed at each place of residence and in each of these
      buffers. Higher levels of exposure to noise were documented in low educated
      neighborhoods. Multilevel logistic regression models documented positive
      associations between road traffic noise and annoyance due to road traffic, after
      adjusting for individual/neighborhood socioeconomic conditions. There was no
      evidence that the association was of different magnitude when noise was measured
      at the place of residence or in the residential neighborhood. However, the
      strength of the association between neighborhood noise exposure and annoyance
      increased when considering a higher percentile in the distribution of noise in
      each neighborhood. Road traffic noise estimated at the place of residence and
      road traffic noise in the residential neighborhood (75th percentile) were
      independently associated with annoyance, when adjusted for each other.
      Interactions of effects indicated that the relationship between road traffic
      noise exposure in the residential neighborhood and annoyance was stronger in
      affluent and high educated neighborhoods. Overall, our findings suggest that it
      is useful to take into account (i) the exposure to transportation noise in the
      residential neighborhood rather than only at the residence, (ii) different
      percentiles of noise exposure in the residential neighborhood, and (iii) the
      socioeconomic characteristics of the residential neighborhood to explain
      variations in annoyance due to road traffic in the neighborhood.

PMID- 24088230
TI  - [Preventing diabetic nephropathy significantly].

PMID- 24088231
TI  - [Acute liver failure].

PMID- 24088233
TI  - [Albuminuria in the diabetic patient: practical management].
AB  - Diabetic Nephropathy is the most common cause of end stage renal disease in
      Western countries. An increased urinary albumin excretion represents a
      characteristic sign of diabetic kidney damage. Regular screening for
      microalbuminuria allows early detection and timely intervention. In overt
      diabetic nephropathy, quantification of albuminuria helps monitoring disease
      progression. Therapeutic interventions to reduce albuminuria retard progression
      of nephropathy and reduce cardiovacular mortality, since albuminuria represents
      an independent cardiovascular risk factor. This review article describes the
      natural history of diabetic nephropathy and discusses practical issues for the
      measurement of albuminuria. Available prophylactic and therapeutic measures,
      particularly glycemic control and inhibition of the renin-angiotensin-aldosteron
      system, are reviewed using an evidence based approach. 

PMID- 24088234
TI  - [Urination disorders in the man: differential diagnoses and therapy of benign
      prostate syndrome].
AB  - Lower urinary tract symptoms in men are highly associated with benign prostate
      syndrome. Nevertheless, a correct diagnosis is required to exclude other
      pathologies. In addition to neurogenic causes other urological differential
      diagnoses can be clarified and treated. If diagnosis of benign prostatic syndrome
      is confirmed, various medical and surgical treatment options are available. 

PMID- 24088235
TI  - [Thrombocyte aggregation inhibitors: what are the risks?].
AB  - The most common risks related to platelet inhibitor therapy are bleeding, drug
      drug interactions and therapeutic failure. The new substances prasugrel and
      ticagrelor are more potent platelet inhibitiors than clopidogrel. This reduces
      the incidence of ischemic events, but also potentially increases the bleeding
      risk. Clopidogrel therapy has up to 20% non-response rates, which can partially
      be explained by genetic polymorphisms and drug-drug interactions. Currently no
      evidence exists that ticagrelor or prasugrel efficacy is affected by genetic
      polymorphisms. The therapy in patients at risk still has to be carefully adapted
      to minimize adverse events. Patients older than 75 years and/or weighing less
      than 60 kg should receive a reduced dose of prasugrel. The combination of
      ticagrelor with strong cytochrome-P450-3A4 inhibitors is contraindicated. 

PMID- 24088236
TI  - [Non-neoplastic esophageal stenosis: not always so benign].
AB  - Esophageal intramural pseudodiverticulosis is a rare pathology whose etiology is
      unknown, but which is frequently associated with three highly prevalent entities:
      esophageal reflux disease, esophageal candidosis and alcoholic esophagitis. With
      conservative treatment the course of these pathologies is usually benign.
      However, some severe cases are resistant to conservative treatment and may
      require more aggressive management. We here present the case of patient suffering
      from a severe esophagitis complicated by chronic mediastinitis with life
      threatening repercussions, requiring esophagectomy as treatment. 

PMID- 24088238
TI  - [Therapy of acute pain with opiates - titrate or bolus administration?].

PMID- 24088239
TI  - [Pneumonia or not? CRP helps to distinguish with average probability].

PMID- 24088244
TI  - Assessing the proton affinities of N,N'-diamidocarbenes.
AB  - The gas-phase proton affinities (PAs) of a series of novel diamidocarbenes (DACs)
      were assessed and compared to various imidazolylidene-based N-heterocyclic
      carbenes (NHCs) through experimental and computational methods. Apart from a
      perfluorinated-phenyl derivative (PA = 233 kcal/mol), the calculated and measured
      PAs for a range of DACs (256-261 kcal/mol) were comparable to those of the NHCs
      (260-266 kcal/mol). Proton transfer from the protonated carbene to various
      reference bases, as observed by mass spectrometry, was inhibited by steric bulk
      and precluded the direct measurement of the PA for the known DACs, N,N'-dimesityl
      4,6-diketo-5,5-dimethylpyrimidin-2-ylidene and N,N'-diisopropylphenyl-4,6-diketo
      5,5-dimethylpyrimidin-2-ylidene. However, DACs featuring less hindered N-aryl
      substituents facilitated proton transfer, and the measured PA values were found
      to be consistent with density functional theory calculations (B3LYP/6-31+G(d)).
      Notably, the PAs of the DACs studied were similar to those of the NHCs,
      indicating that the former retain many of the nucleophilic characteristics
      intrinsic to their parent diaminocarbenes and that the observed differences in
      chemical reactivity may be primarily attributed to an enhanced electrophilicity. 

PMID- 24088246
TI  - Limited fluid resuscitation attenuates lung and intestine injury caused by
      hemorrhagic shock in rats.
AB  - BACKGROUND AND OBJECTIVE: Different volume fluid resuscitations were closely
      associated with different cytokine responses, which could influence shock-induced
      lung and intestinal destruction. The aim of the study is to compare the effects
      of limited and traditional resuscitation on the levels of inflammatory response
      and lung and intestinal injury of hemorrhagic shock (HS) rats. METHOD: Sprague
      Dawley male rats were subjected to a blood pressure-controlled hemorrhage group
      following three kinds of resuscitation using lactated Ringer's (LR) solution (45,
      30, 15 ml/kg.hr, respectively) and unresuscitation group. Then six rats of each
      group were sacrificed at 24, 48, and 72 hr, respectively. RESULTS: The levels of
      plasma TNF-alpha, the plasma lactic acid, the intestinal permeability, and the
      ratio of wet weight to dry weight of lung and intestinal were lower in the group
      of 15 ml/kg.hr than other groups (p < .05). The lung and intestinal injury were
      more severe in group 45 ml/kg.hr than other groups in 24, 48, and 72 hr (p <
      .05). CONCLUSION: Comparing with conventional fluid resuscitation, limited fluid
      resuscitation (LFR) could not only decrease the levels of lactic acid and pro
      inflammatory factors but also attenuate the intestinal and lung injury.

PMID- 24088245
TI  - Drug repositioning for orphan genetic diseases through Conserved Anticoexpressed
      Gene Clusters (CAGCs).
AB  - BACKGROUND: The development of new therapies for orphan genetic diseases
      represents an extremely important medical and social challenge. Drug
      repositioning, i.e. finding new indications for approved drugs, could be one of
      the most cost- and time-effective strategies to cope with this problem, at least
      in a subset of cases. Therefore, many computational approaches based on the
      analysis of high throughput gene expression data have so far been proposed to
      reposition available drugs. However, most of these methods require gene
      expression profiles directly relevant to the pathologic conditions under study,
      such as those obtained from patient cells and/or from suitable experimental
      models. In this work we have developed a new approach for drug repositioning,
      based on identifying known drug targets showing conserved anti-correlated
      expression profiles with human disease genes, which is completely independent
      from the availability of 'ad hoc' gene expression data-sets. RESULTS: By
      analyzing available data, we provide evidence that the genes displaying conserved
      anti-correlation with drug targets are antagonistically modulated in their
      expression by treatment with the relevant drugs. We then identified clusters of
      genes associated to similar phenotypes and showing conserved anticorrelation with
      drug targets. On this basis, we generated a list of potential candidate drug
      disease associations. Importantly, we show that some of the proposed associations
      are already supported by independent experimental evidence. CONCLUSIONS: Our
      results support the hypothesis that the identification of gene clusters showing
      conserved anticorrelation with drug targets can be an effective method for drug
      repositioning and provide a wide list of new potential drug-disease associations
      for experimental validation.

PMID- 24088247
TI  - Clinical features and outcomes of neck lymphatic metastasis in ovarian epithelial
      carcinoma.
AB  - BACKGROUND: Neck lymph node metastasis (NLNM) in epithelial ovarian cancer (EOC)
      is rare and treated as advanced stage cancer. However, ovarian cancer with
      lymphatic metastasis may manifest a different clinical course from peritoneal
      carcinomatosis. METHODS: The authors retrospectively assessed 20 patients with
      EOC and pathologically diagnosed as NLNM between January 2001 and December 2010.
      The patients were divided into two groups according to the time of NLNM
      identification. Statistical methods included Kaplan-Meier, log-rank, and Cox
      regression analysis. RESULTS: Eleven patients were diagnosed with NLNM at the
      same time of surgical exploration of EOC (Group A) and nine patients at cancer
      recurrence 43.3 months after initial surgery (Group B). In Group A, patients with
      tumors confined to the pelvic cavity had no recurrence or had isolated lymph node
      recurrence (ILNR), and survived longer than patients with abdominal tumor
      spreading (P = 0.0007). In Group B, 2 patients showed ILNR. The median survival
      time after NLNM was 42 months in Group A and 6 months in Group B (P = 0.01). Cox
      model demonstrated that non-serous histology, brain metastasis, and NLNM
      identified at cancer recurrence were major predictors for poor overall survival
      (Hazard ratio [HR] = 18.67, 6.93, and 4.52; P = 0.01, 0.02, and 0.04,
      respectively). CONCLUSIONS: A subgroup of EOC patients with NLNM who presented
      limited pelvic cancer had much better overall survival than patients who had
      cancer spreading beyond the pelvic cavity or were diagnosed with NLNM at cancer
      recurrence.

PMID- 24088248
TI  - Quality of life impairment associated with body dissatisfaction in a general
      population sample of women.
AB  - BACKGROUND: In order to elucidate the individual and community health burden of
      body dissatisfaction (BD), we examined impairment in quality of life associated
      with BD in a large, general population sample of women. METHODS: Self-report
      measures of BD, health-related quality of life (SF-12 Physical and Mental
      Component Summary scales) and subjective quality of life (WHOQOL-BREF
      Psychological Functioning and Social Relationships subscales) were completed by
      5,255 Australian women aged 18 to 42 years. RESULTS: Most participants (86.9%)
      reported some level of dissatisfaction with their weight or shape and more than
      one third (39.4%) reported moderate to marked dissatisfaction. Higher levels of
      BD were associated with poorer quality of life for all items of both quality of
      life measures, the degree of impairment being proportional to the degree of BD.
      Associations were strongest for items tapping mental health and psychosocial
      functioning, although greater BD was associated with substantially increased risk
      of impairment in certain aspects of physical health even when controlling for
      body weight. Post-hoc analysis indicated that the observed associations between
      BD and quality of life impairment were not accounted for by an association
      between BD and eating disorder symptoms. CONCLUSIONS: In women, BD is associated
      with marked impairment in aspects of quality of life relating to mental health
      and psycho-social functioning and at least some aspects of physical health,
      independent of its association with body weight and eating disorder symptoms.
      Greater attention may need to be given to BD as a public health problem. The fact
      that BD is "normative" should not be taken to infer that it is benign.

PMID- 24088249
TI  - Dietary diversity of formal and informal residents in Johannesburg, South Africa.
AB  - BACKGROUND: This paper considers the question of dietary diversity as a proxy for
      nutrition insecurity in communities living in the inner city and the urban
      informal periphery in Johannesburg. It argues that the issue of nutrition
      insecurity demands urgent and immediate attention by policy makers. METHODS: A
      cross-sectional survey was undertaken for households from urban informal (n =
      195) and urban formal (n = 292) areas in Johannesburg, South Africa. Foods
      consumed by the respondents the previous day were used to calculate a Dietary
      Diversity Score; a score < 4 was considered low. RESULTS: Statistical comparisons
      of means between groups revealed that respondents from informal settlements
      consumed mostly cereals and meat/poultry/fish, while respondents in formal
      settlements consumed a more varied diet. Significantly more respondents living in
      informal settlements consumed a diet of low diversity (68.1%) versus those in
      formal settlements (15.4%). When grouped in quintiles, two-thirds of respondents
      from informal settlements fell in the lowest two, versus 15.4% living in formal
      settlements. Households who experienced periods of food shortages during the
      previous 12 months had a lower mean DDS than those from food secure households
      (4.00 +/- 1.6 versus 4.36 +/- 1.7; p = 0.026). CONCLUSIONS: Respondents in the
      informal settlements were more nutritionally vulnerable. Achieving nutrition
      security requires policies, strategies and plans to include specific nutrition
      considerations.

PMID- 24088250
TI  - Possible involvement of pirfenidone metabolites in the antifibrotic action of a
      therapy for idiopathic pulmonary fibrosis.
AB  - Pirfenidone (PFD) is the first and only clinically used antifibrotic drug for the
      treatment of idiopathic pulmonary fibrosis (IPF). This study evaluated the
      antifibrotic effects of two metabolites of PFD, 5-hydroxypirfenidone (PFD-OH) and
      5-carboxypirfenidone (PFD-COOH), on WI-38 cells in an in vitro lung fibroblast
      model. The inhibitory effects of PFD-OH and PFD-COOH on transforming growth
      factor-beta1 (TGF-beta1)-induced collagen synthesis in WI-38 cells were evaluated
      by measuring intracellular hydroxyproline, a major component of the protein
      collagen. PFD-OH and PFD-COOH at 300 and 1000 uM concentrations significantly
      decreased the TGF-beta1-induced hydroxyproline content in WI-38 cells. These
      results indicate that PFD-OH and PFD-COOH have antifibrotic activities, which
      inhibit collagen synthesis in fibroblasts. This study suggests that the
      concentrations of PFD and its metabolites should be considered in clinical
      therapy for IPF.

PMID- 24088251
TI  - Sodium alginate inhibits methotrexate-induced gastrointestinal mucositis in rats.
AB  - Gastrointestinal mucositis is one of the most prevalent side effects of
      chemotherapy. Methotrexate is a pro-oxidant compound that depletes dihydrofolate
      pools and is widely used in the treatment of leukemia and other malignancies.
      Through its effects on normal tissues with high rates of proliferation,
      methotrexate treatment leads to gastrointestinal mucositis. In rats, methotrexate
      induced gastrointestinal mucositis is histologically characterized by crypt loss,
      callus fusion and atrophy, capillary dilatation, and infiltration of mixed
      inflammatory cells. The water-soluble dietary fiber sodium alginate (AL-Na) is
      derived from seaweed and has demonstrated muco-protective and hemostatic effects
      on upper gastrointestinal ulcers. In the present study, we evaluated the effects
      of AL-Na on methotrexate-induced small intestinal mucositis in rats. Animals were
      subcutaneously administered methotrexate at a dosage of 2.5 mg/kg once daily for
      3 d. Rats were treated with single oral doses of AL-Na 30 min before and 6 h
      after methotrexate administration. On the 4th day, small intestines were removed
      and weighed. Subsequently, tissues were stained with hematoxylin-eosin and
      bromodeoxyuridine. AL-Na significantly prevented methotrexate-induced small
      intestinal mucositis. Moreover, AL-Na prevented decreases in red blood cell
      numbers, hemoglobin levels, and hematocrit levels. These results suggest the
      potential of AL-Na as a therapy for methotrexate-induced small intestinal
      mucositis.

PMID- 24088252
TI  - Anti-Helicobacter pylori and antiulcerogenic activities of the root cortex of
      Paeonia suffruticosa.
AB  - In this study, we evaluated the gastric protective activities of mokdanpi in
      vitro. Further, we used experimental ulcer models to identify the active
      ingredients of mokdanpi. As a preliminary evaluation of mokdanpi ethanolic
      extract and its ingredients, we assessed its radical scavenging activities. In
      addition, its antimicrobial activity against Helicobacter pylori (H. pylori) was
      investigated. The antiulcerogenic activity of the active ingredients was
      evaluated in pylorus-ligated rats, an HCl/ethanol-induced and an absolute ethanol
      induced ulcer model. We confirmed the scavenging effect of the ethanolic extract
      of mokdanpi and its ingredients against 2,2-diphenyl-1-picrylhydrazyl, nitric
      oxide and superoxide radicals, and we demonstrated that mokdanpi could inhibit
      the colonization of H. pylori. In an HCl-ethanol-induced ulcer model, gallic acid
      and catechin (100 mg/kg) inhibited 40.6% and 41.7% of gastric lesions,
      respectively. Catechin (100 mg/kg) significantly reduced (p<0.05) the gastric
      secretion induced by pylorus ligature in rats in comparison to the control group.
      Gallic acid (100 mg/kg) significantly increased (p<0.05) the mucus contents in an
      ethanol-induced ulcer model. The antioxidant ingredients (catechin and gallic
      acid) present in mokdanpi play a major role in antiulcerogenic activity, and
      demonstrate novel activity against H. pylori.

PMID- 24088253
TI  - Sesamin induces cell cycle arrest and apoptosis through the inhibition of signal
      transducer and activator of transcription 3 signalling in human hepatocellular
      carcinoma cell line HepG2.
AB  - Sesamin, one of the most abundant lignans in sesame seeds, has been shown to
      exhibit various pharmacological effects. The aim of this study was to elucidate
      whether sesamin promotes cell cycle arrest and induces apoptosis in HepG2 cells
      and further to explore the underlying molecular mechanisms. Here, we found that
      sesamin inhibited HepG2 cell growth by inducing G2/M phase arrest and apoptosis.
      Furthermore, sesamin suppressed the constitutive and interleukin (IL)-6-induced
      signal transducer and activator of transcription 3 (STAT3) signalling pathway in
      HepG2 cells, leading to regulate the downstream genes, including p53, p21, cyclin
      proteins and the Bcl-2 protein family. Our studies showed that STAT3 signalling
      played a key role in sesamin-induced G2/M phase arrest and apoptosis in HepG2
      cells. These findings provided a molecular basis for understanding of the effects
      of sesamin in hepatocellular carcinoma tumour cell proliferation. Therefore,
      sesamin may thus be a potential chemotherapy drug for liver cancer. 

PMID- 24088254
TI  - Comparison of (-)-epigallocatechin-3-O-gallate (EGCG) and O-methyl EGCG
      bioavailability in rats.
AB  - (-)-Epigallocatechin-3-O-(3-O-methyl)gallate (EGCG3"Me) and (-)-epigallocatechin
      3-O-(4-O-methyl)gallate (EGCG4"Me) are O-methyl derivatives of (-)
      epigallocatechin-3-O-gallate (EGCG) present in tea cultivars such as Benifuuki.
      Although O-methyl EGCGs have various bioactivities, their bioavailabilities have
      not been determined. In this study, we compared the bioavailability of EGCG and O
      methyl EGCGs in rats, and clarified the pharmacokinetics of O-methyl EGCGs.
      Following oral administration (100 mg/kg), the areas under the concentration-time
      curves (AUCs) for EGCG, EGCG3"Me, and EGCG4"Me were 39.6 +/- 14.2 ug.h/L, 317.2
      +/- 43.7 ug.h/L, and 51.9 +/- 11.0 ug.h/L, respectively. The AUC after
      intravenous administration (10 mg/kg) was 2772 +/- 480 ug.h/L for EGCG, 8209 +/-
      549 ug.h/L for EGCG3"Me, and 2465 +/- 262 ug.h/L for EGCG4"Me. The
      bioavailability of EGCG3"Me (0.38%) was the highest (EGCG: 0.14% and EGCG4"Me:
      0.21%). The distribution volume of EGCG3"Me (0.26 +/- 0.02 L/kg) was the lowest
      (EGCG: 0.94 +/- 0.16 L/kg and EGCG4"Me: 0.93 +/- 0.14 L/kg). These results
      suggested that the higher AUC of EGCG3"Me after oral administration was related
      to its high bioavailability and low distribution volume. These findings supported
      the stronger bioactivity of EGCG3"Me in vivo.

PMID- 24088255
TI  - Inhalation of the essential oil of Piper guineense from Cameroon shows sedative
      and anxiolytic-like effects in mice.
AB  - The aromatherapeutical potential of Piper guineense essential oil was
      investigated in mice via inhalation administration, and the active compounds were
      identified. An open field test and light/dark transition test were used to
      evaluate the sedative and anxiolytic activities of this essential oil,
      respectively. P. guineense essential oil showed significant sedative activity at
      an effective dose of 4.0 * 10(-5) mg per cage compared to the control group. It
      also showed potent anxiolytic effect at a dose of 4.0 * 10(-6) mg per cage. The
      main compounds of P. guineense essential oil were linalool (41.8%) and 3,5
      dimethoxytoluene (10.9%). These two main compounds were shown to play a major
      role in the sedative activity of P. guineense essential oil. These results
      suggest that inhalation of P. guineense essential oil might induce a mild
      tranquilizing effect.

PMID- 24088256
TI  - Assessment of effects of chronic hydrogen sulfide poisoning on cytochrome P450
      isoforms activity of rats by cocktail approach.
AB  - Hydrogen sulfide (H2S) is one of the neurotoxic gases with suffocating and
      irritating. Its main target organs of toxic effects are the central nervous
      system and respiratory system. Cocktail method was used to evaluate the influence
      of chronic hydrogen sulfide poisoning on the activities of cytochrome P450
      (CYP450) isoforms CYP1A2, CYP2C9, CYP2B6 and CYP2D6, which were reflected by the
      changes of pharmacokinetic parameters of 4 specific probe drugs phenacetin,
      tolbutamide bupropion and metroprolol, respectively. The experimental rats were
      randomly divided into two groups, control group and chronic hydrogen sulfide
      poisoning group. The chronic hydrogen sulfide poisoning group rats were inhaled
      20 ppm for 1 h twice a day for 40 d. The mixture of 4 probes was given to rats
      through sublingual veins and the blood samples were obtained at a series of time
      points through the caudal vein. The concentrations of probe drugs in rat plasma
      were measured by liquid chromatography-mass spectrometry (LC-MS). In the
      experiment for chronic hydrogen sulfide poisoning and control group, there was a
      statistically significant difference in the area under the plasma concentration
      time curve from zero to infinity (AUC(0-infinity)), plasma clearance (CL) and
      maximum plasma concentration (C(max)) for phenacetin and bupropion, while there
      was no statistical pharmacokinetics difference for tolbutamide and metoprolol.
      Chronic hydrogen sulfide poisoning could induce the activity of CYP1A2 and CYP2B6
      of rats.

PMID- 24088257
TI  - The polymerization agent, 2-methyl-4'-(methylthio)-2-morpholinopropiophenone
      induces caspases-3/7 in human blood mononuclear cells in vitro.
AB  - Our previous studies detected the presence of a photoinitiator 2-methyl-4'
      (methylthio)-2-morpholinopropiophenone (MTMP) in an intravenous (i.v.) injection
      bag solution. Importantly, MTMP has demonstrated cytotoxicity for normal human
      peripheral blood (PB) mononuclear cells (MNC). Cell death pathways have two well
      known modes, apoptosis and necrosis. But it has not been clear whether MTMP
      induced apoptosis or necrosis in normal human PB MNC. In the present in vitro
      study, we examined normal human PB MNC for the frequencies of apoptosis and
      necrosis and changes upon exposure to MTMP. We observed time-dependent changes in
      MNC viability with MTMP. We also assessed the activity of caspases-3/7. The
      results demonstrated that MTMP induced apoptosis in normal human PB MNC after 24
      h. In addition, MTMP induced caspases-3/7 in a time-dependent manner. In
      conclusion, we suggest that MTMP induces apoptosis in a caspase-dependent pathway
      in vitro.

PMID- 24088258
TI  - Electrophysiological effects of an anti-influenza drug oseltamivir on the guinea
      pig atrium: comparison with those of pilsicainide.
AB  - We assessed the effects of oseltamivir on the conduction velocity and effective
      refractory period in the guinea-pig atrium in comparison with those of a class Ic
      antiarrhythmic drug pilsicainide. The recording and stimulating electrodes were
      attached on the epicardium close to the sinus nodal region and on the left atrial
      appendage. Oseltamivir (10-100 uM) as well as pilsicainide (1-10 uM) decreased
      the atrial conduction velocity in a frequency-dependent manner. Both drugs also
      increased the effective refractory period in both atria; but the frequency
      dependent property of oseltamivir was lacking in the left atrium, and it was less
      obvious in the right atrium compared with that of pilsicainide. These results
      suggest that oseltamivir can directly modify the electrophysiological functions
      in the guinea-pig atrium possibly via combination of Na(+) and K(+) channel
      blocking actions.

PMID- 24088259
TI  - Nasal carriage rate of methicillin resistant Staphylococcus aureus among Dessie
      Referral Hospital Health Care Workers; Dessie, Northeast Ethiopia.
AB  - BACKGROUND: Staphylococcus aureus is a common cause of community and hospital
      acquired infections. One of the important sources of staphylococci for nosocomial
      infection is nasal carriage among hospital personnel. Emergence of drug resistant
      strains especially methicillin resistant Staphylococcus aureus is a serious
      problem in hospital environments. The aim of this study was to determine the
      nasal carriage rate of methicillin resistant Staphylococcus aureus among Dessie
      Referral Hospital healthcare-workers in Ethiopia. METHODS: A cross sectional
      study was conducted on a total of 118 healthcare workers. Nasal swabs were
      collected and cultured on Mannitol Salt Agar. Slide coagulase test was performed.
      An oxacillin susceptibility test was carried out on Muller Hinton agar using
      modified Kirby-Bauer disc diffusion method. RESULTS: Of the 118 healthcare
      workers, 34 (28.8%) carried S. aureus of which 15 were methicillin resistant.
      Therefore, 12.7% of all HCWs were identified as MRSA carriers. The rate of
      methicillin resistance among all S. aureus isolates was 44.1% (15/34). MRSA
      carriage was particularly high among nurses (21.2%). The highest rate of MRSA
      carriers (57.1%) were workers of surgical wards. CONCLUSIONS: The high rate of
      nasal MRSA carriage among healthcare workers found in this study indicates the
      need for adjusted infection control measures to prevent MRSA transmission in our
      healthcare setting.

PMID- 24088260
TI  - Proposal of a quantitative PCR-based protocol for an optimal Pseudomonas
      aeruginosa detection in patients with cystic fibrosis.
AB  - BACKGROUND: The lung of patients with cystic fibrosis (CF) is particularly
      sensitive to Pseudomonas aeruginosa. This bacterium plays an important role in
      the poor outcome of CF patients. During the disease progress, first acquisition
      of P. aeruginosa is the key-step in the management of CF patients. Quantitative
      PCR (qPCR) offers an opportunity to detect earlier the first acquisition of P.
      aeruginosa by CF patients. Given the lack of a validated protocol, our goal was
      to find an optimal molecular protocol for detection of P. aeruginosa in CF
      patients. METHODS: We compared two formerly described qPCR formats in early
      detection of P. aeruginosa in CF sputum samples: a qPCR targeting oprL gene, and
      a multiplex PCR targeting gyrB and ecfX genes. RESULTS: Tested in vitro on a
      large panel of P. aeruginosa isolates and others gram-negative bacilli, oprL qPCR
      exhibited a better sensitivity (threshold of 10 CFU/mL versus 730 CFU/mL),
      whereas the gyrB/ecfX qPCR exhibited a better specificity (90% versus 73%). These
      results were validated ex vivo on 46 CF sputum samples positive for P. aeruginosa
      in culture. Ex vivo assays revealed that qPCR detected 100 times more bacterial
      cells than culture-based method did. CONCLUSION: Based on these results, we
      proposed a reference molecular protocol combining the two qPCRs, which offers a
      sensitivity of 100% with a threshold of 10 CFU/mL and a specificity of 100%. This
      combined qPCR-based protocol can be adapted and used for other future prospective
      studies.

PMID- 24088261
TI  - Translation of proteomic biomarkers into FDA approved cancer diagnostics: issues
      and challenges.
AB  - Tremendous efforts have been made over the past few decades to discover novel
      cancer biomarkers for use in clinical practice. However, a striking discrepancy
      exists between the effort directed toward biomarker discovery and the number of
      markers that make it into clinical practice. One of the confounding issues in
      translating a novel discovery into clinical practice is that quite often the
      scientists working on biomarker discovery have limited knowledge of the
      analytical, diagnostic, and regulatory requirements for a clinical assay. This
      review provides an introduction to such considerations with the aim of generating
      more extensive discussion for study design, assay performance, and regulatory
      approval in the process of translating new proteomic biomarkers from discovery
      into cancer diagnostics. We first describe the analytical requirements for a
      robust clinical biomarker assay, including concepts of precision, trueness,
      specificity and analytical interference, and carryover. We next introduce the
      clinical considerations of diagnostic accuracy, receiver operating characteristic
      analysis, positive and negative predictive values, and clinical utility. We
      finish the review by describing components of the FDA approval process for
      protein-based biomarkers, including classification of biomarker assays as medical
      devices, analytical and clinical performance requirements, and the approval
      process workflow. While we recognize that the road from biomarker discovery,
      validation, and regulatory approval to the translation into the clinical setting
      could be long and difficult, the reward for patients, clinicians and scientists
      could be rather significant. 

PMID- 24088262
TI  - Calculation of Tajima's D and other neutrality test statistics from low depth
      next-generation sequencing data.
AB  - BACKGROUND: A number of different statistics are used for detecting natural
      selection using DNA sequencing data, including statistics that are summaries of
      the frequency spectrum, such as Tajima's D. These statistics are now often being
      applied in the analysis of Next Generation Sequencing (NGS) data. However,
      estimates of frequency spectra from NGS data are strongly affected by low
      sequencing coverage; the inherent technology dependent variation in sequencing
      depth causes systematic differences in the value of the statistic among genomic
      regions. RESULTS: We have developed an approach that accommodates the uncertainty
      of the data when calculating site frequency based neutrality test statistics. A
      salient feature of this approach is that it implicitly solves the problems of
      varying sequencing depth, missing data and avoids the need to infer variable
      sites for the analysis and thereby avoids ascertainment problems introduced by a
      SNP discovery process. CONCLUSION: Using an empirical Bayes approach for fast
      computations, we show that this method produces results for low-coverage NGS data
      comparable to those achieved when the genotypes are known without uncertainty. We
      also validate the method in an analysis of data from the 1000 genomes project.
      The method is implemented in a fast framework which enables researchers to
      perform these neutrality tests on a genome-wide scale.

PMID- 24088263
TI  - Intravesical stone formation several years after hysterectomy: a case report.
AB  - INTRODUCTION: Most bladder stones develop in patients with bladder outlet
      obstruction. Intravesical stone formation after surgery outside the urinary
      bladder is rare. CASE PRESENTATION: A 54-year-old Taiwanese woman with lower
      urinary tract symptoms following a hysterectomy 14 years ago presented to our
      hospital. The intravesical calculus had developed from non-absorbable sutures and
      hung on the dome of the urinary bladder. The stone and residuum of the suture
      were retrieved by performing an endoscopic procedure. CONCLUSIONS: The presence
      of an intravesical stone should be suspected in patients with a history of
      hysterectomy who have symptoms in the lower urinary tract. A hanging stone on the
      dome of the urinary bladder implies that suture materials migrate into the
      urinary bladder. The complication can be prevented by the routine use of
      absorbable material and double-checking with cystoscopy.

PMID- 24088264
TI  - An evaluation of allele frequency estimation accuracy using pooled sequencing
      data.
AB  - Next generation sequencing technology has matured, and with its current
      affordability, will replace the SNP chip as the genotyping tool of choice. Even
      with the current affordability of NGS, large scale studies will require careful
      study design to reduce cost. In this study, we designed an experiment to assess
      the accuracy of allele frequency estimated from pooled sequencing data. We
      compared the allele frequency estimated from sequencing data with the allele
      frequency estimated from individual SNP chip data and observed high correlations
      between them. However, by calculating error rate, we found that many SNPs had
      their allele frequency estimated from sequencing data significantly different
      from allele frequency estimated from SNP chip data. In conclusion, we found
      correlation is not an ideal measurement for comparing allele frequencies. And for
      the purpose of estimating allele frequency, we do not recommend using pooling
      with NGS as a cheaper alternative to genotype each sample individually. 

PMID- 24088265
TI  - Models for the prediction of melanocortin-4 receptor agonist activity of 4
      substituted piperidin-4-ol.
AB  - In the present study both classification and correlation techniques have been
      successfully employed for the development of the models of diverse nature for the
      prediction of melanocortin 4-receptor (MC4 R) agonist activity using a dataset
      comprising of 56 analogues of 4-substituted piperidine-4-ol derivatives. Decision
      tree (DT), random forest (RF), moving average analysis (MAA) and multiple linear
      regression (MLR) were utilised for development of the said models. The
      statistical significance of models was assessed through specificity, sensitivity,
      overall accuracy, Mathew's correlation coefficient (MCC) and intercorrelation
      analysis. High accuracy of prediction up to 98% was observed using these models.
      Proposed models offer vast potential for providing lead structures for the
      development of potent therapeutic agents for the treatment of male sexual
      dysfunction. 

PMID- 24088266
TI  - Characterisation of the flexibility of substrate binding loop in the binding of
      direct InhA inhibitors.
AB  - The substrate binding loop (SBL) of inhA shows conformational changes on binding
      of direct inhA inhibitors (DIIs). The knowledge of conformational changes and its
      importance in binding of DII to inhA has not been explored before. This study
      initially focused on studying the conformational changes of SBL in selected inhA
      crystal structures. These conformational changes are measured as angle of
      rotation for SBL from the static hinge region, Ile194, in the crystal structures.
      The maximal angle difference of ~41 degrees  was observed between most open and
      closed conformation of SBL. To gain insights into these conformational changes,
      comparative molecular dynamics simulations of inhA bound with a direct inhibitor
      (Genz10850) and apoprotein were performed. A considerable variation in the angle
      of rotation (~24 degrees  to ~12 degrees ) for the SBL which led to the closed
      conformation was observed during binding of Genz10850 with a consistent increase
      in electrostatic energy, whereas no change was observed in apoprotein. Hence,
      conformational changes in the SBL under the influence of inhibitor can be
      utilised as a parameter for enhanced binding inhibitor with inhA to screen the
      potent DIIs. 

PMID- 24088267
TI  - Multidrug resistance protein P-gp interaction with nanoparticles (fullerenes and
      carbon nanotube) to assess their drug delivery potential: a theoretical molecular
      docking study.
AB  - P-glycoprotein (P-gp)-mediated efflux system plays an important role to maintain
      chemical balance in mammalian cells for endogenous and exogenous chemical
      compounds. However, despite the extensive characterisation of P-gp potential
      interaction with drug-like molecules, the interaction of carbon nanoparticles
      with this type of protein molecule is poorly understood. Thus, carbon
      nanoparticles were analysed, such as buckminsterfullerenes (C20, C60, C70),
      capped armchair single-walled carbon nanotube (SWCNT or C168), and P-gp
      interactions using different molecular docking techniques, such as gradient
      optimisation algorithm (ADVina), Lamarckian genetic algorithm (FastDock), and
      shape-based approach (PatchDock) to estimate the binding affinities between these
      structures. The theoretical results represented in this work show that fullerenes
      might be P-gp binders because of low levels of Gibbs free energy of binding
      (DeltaG) and potential of mean force (PMF) values. Furthermore, the SWCNT binding
      is energetically unfavourable, leading to a total decrease in binding affinity by
      elevation of the residual area (Ares), which also affects the pi-pi stacking
      mechanisms. Further, the obtained data could potentially call experimental
      studies using carbon nanostructures, such as SWCNT for development of drug
      delivery vehicles, to administer and assess drug-like chemical compounds to the
      target cells since organisms probably did not develop molecular sensing elements
      to detect these types of carbon molecules. 

PMID- 24088268
TI  - Sample size calculation for differential expression analysis of RNA-seq data
      under Poisson distribution.
AB  - Sample size determination is an important issue in the experimental design of
      biomedical research. Because of the complexity of RNA-seq experiments, however,
      the field currently lacks a sample size method widely applicable to differential
      expression studies utilising RNA-seq technology. In this report, we propose
      several methods for sample size calculation for single-gene differential
      expression analysis of RNA-seq data under Poisson distribution. These methods are
      then extended to multiple genes, with consideration for addressing the multiple
      testing problem by controlling false discovery rate. Moreover, most of the
      proposed methods allow for closed-form sample size formulas with specification of
      the desired minimum fold change and minimum average read count, and thus are not
      computationally intensive. Simulation studies to evaluate the performance of the
      proposed sample size formulas are presented; the results indicate that our
      methods work well, with achievement of desired power. Finally, our sample size
      calculation methods are applied to three real RNA-seq data sets. 

PMID- 24088269
TI  - Fatigue in myasthenia gravis: is it more than muscular weakness?
AB  - BACKGROUND: Few studies have focused on fatigue in myasthenia gravis (MG), and
      fatigue in relation to the autonomic system has never been systematically
      explored in these patients. The study aimed to document the prevalence of MG
      related fatigue in ethnic Norwegians and to examine whether MG severity is
      associated with symptoms of autonomic disturbance, which in turn is associated
      with fatigue and functional disability. METHODS: Eighty two of the 97 who
      fulfilled the study inclusion criteria participated in the study. Controls were
      410 age- and sex-matched subjects drawn from a normative sample (n = 2136)
      representative of the Norwegian population. Bivariate analyses and multivariate
      linear regression analyses were used to assess associations between questionnaire
      reported MG severity, symptoms of autonomic disturbance, fatigue (mental and
      physical) and functional disability. RESULTS: Forty-four per cent (36/82) of
      patients fulfilled the criteria for fatigue compared with 22% (90/410) of
      controls (odds ratio 2.0; p = 0.003). Twenty-one per cent of patients (17/82) met
      the criteria for chronic fatigue versus 12% (48/410) of controls (odds ratio
      1.96; p = 0.03). MG patients had higher total fatigue scores than controls (p <
      0.001) and a high prevalence of autonomic symptoms, especially poor
      thermoregulation and sleep disturbance. According to multivariate analyses
      controlled for MG score, symptoms of autonomic disturbances were independently
      positively associated with fatigue (p < 0.001), and fatigue was independently
      negatively associated with functional level (p < 0.001). CONCLUSION: Norwegian
      ethnic patients with MG have higher levels of fatigue and a higher prevalence of
      chronic fatigue than controls, even in patients in full remission. MG severity is
      highly suggestive to be associated with symptoms of autonomic disturbance, which
      in turn is associated with fatigue and the level of functional disability.

PMID- 24088270
TI  - Dental status, dental rehabilitation procedures, demographic and oncological data
      as potential risk factors for infected osteoradionecrosis of the lower jaw after
      radiotherapy for oral neoplasms: a retrospective evaluation.
AB  - PURPOSE: Retrospective evaluation of the dental status of patients with oral
      cancer before radiotherapy, the extent of dental rehabilitation procedures,
      demographic and radiotherapy data as potential risk factors for development of
      infected osteoradionecrosis of the lower jaw. METHODS: A total of 90 patients who
      had undergone radiotherapy for oral cancer were included into this retrospective
      evaluation. None of them had distant metastases. After tumour surgery the
      patients were referred to an oral and maxillofacial surgeon for dental
      examination and the necessary dental rehabilitation procedures inclusive
      potential tooth extraction combined with primary soft tissue closure. Adjuvant
      radiotherapy was started after complete healing of the gingiva (> 7 days after
      potential extraction). The majority of patients (n = 74) was treated with
      conventionally fractionated radiotherapy with total doses ranging from 50-70Gy
      whereas further 16 patients received hyperfractionated radiotherapy up to 72Gy.
      The records of the clinical data were reviewed. Furthermore, questionnaires were
      mailed to the patients' general practitioners and dentists in order to get more
      data concerning tumour status and osteoradionecrosis during follow-up. RESULTS:
      The patients' dental status before radiotherapy was generally poor. On average 10
      teeth were present, six of them were regarded to remain conservable. Extensive
      dental rehabilitation procedures included a mean of 3.7 tooth extractions.
      Chronic periodontitis with severe attachment loss was found in 40%, dental
      biofilm in 56%. An infected osteoradionecrosis (IORN) grade II according to
      (Schwartz et al., Am J Clin Oncol 25:168-171, 2002) was diagnosed in 11 of the 90
      patients (12%), mostly within the first 4 years after radiotherapy. We could not
      find significant prognostic factors for the occurrence of IORN, but a trendwise
      correlation with impaired dental status, rehabilitation procedures, fraction size
      and tumour outcome. CONCLUSION: The occurrence of IORN is an important long-term
      side effect of radiotherapy for oral cancers. From this data we only can conclude
      that a poor dental status, conventional fractionation and local tumour
      progression may enhance the risk of IORN which is in concordance with the
      literature.

PMID- 24088271
TI  - Early treatment with IgM-enriched intravenous immunoglobulin does not mitigate
      critical illness polyneuropathy and/or myopathy in patients with multiple organ
      failure and SIRS/sepsis: a prospective, randomized, placebo-controlled, double
      blinded trial.
AB  - INTRODUCTION: Critical illness polyneuropathy and/or myopathy (CIPNM) is a severe
      complication of critical illness. Retrospective data suggest that early
      application of IgM-enriched intravenous immunoglobulin (IVIG) may prevent or
      mitigate CIPNM. Therefore, the primary objective was to assess the effect of
      early IgM-enriched IVIG versus placebo to mitigate CIPNM in a prospective
      setting. METHODS: In this prospective, randomized, double-blinded and placebo
      controlled trial, 38 critically ill patients with multiple organ failure (MOF),
      systemic inflammatory response syndrome (SIRS)/sepsis, and early clinical signs
      of CIPNM were included. Patients were randomly assigned to be treated either with
      IgM-enriched IVIG or placebo over a period of three days. CIPNM was measured by
      the CIPNM severity sum score based on electrophysiological stimulation of the
      median, ulnar, and tibial nerves on days 0, 4, 7, 14 and on the histological
      evaluation of muscle biopsies on days 0 and 14 and ranged from 0 (no CIPNM) to 8
      (very severe CIPNM). RESULTS: A total of 38 critically ill patients were included
      and randomized to receive either IgM-enriched IVIG (n = 19) or placebo (n = 19).
      Baseline characteristics were similar between the two groups. CIPNM could not be
      improved by IVIG treatment, represented by similar CIPNM severity sum scores on
      day 14 (IVIG vs. placebo: 4.8 +/- 2.0 vs. 4.5 +/- 1.8; P = 0.70). CIPNM severity
      sum score significantly increased from baseline to day 14 (3.5 +/- 1.6 vs. 4.6 +/
      1.9; P = 0.002). After an interim analysis the study was terminated early due to
      futility in reaching the primary endpoint. CONCLUSIONS: Early treatment with IVIG
      did not mitigate CIPNM in critically ill patients with MOF and SIRS/sepsis. TRIAL
      REGISTRATION: Clinicaltrials.gov: NCT01867645.

PMID- 24088272
TI  - Internet and social media for health-related information and communication in
      health care: preferences of the Dutch general population.
AB  - BACKGROUND: Health care is increasingly featured by the use of Web 2.0
      communication and collaborative technologies that are reshaping the way patients
      and professionals interact. These technologies or tools can be used for a variety
      of purposes: to instantly debate issues, discover news, analyze research, network
      with peers, crowd-source information, seek support, and provide advice. Not all
      tools are implemented successfully; in many cases, the nonusage attrition rates
      are high. Little is known about the preferences of the Dutch general population
      regarding the use of the Internet and social media in health care. OBJECTIVE: To
      determine the preferences of the general population in the Netherlands regarding
      the use of the Internet and social media in health care. METHODS: A cross
      sectional survey was disseminated via a popular Dutch online social network.
      Respondents were asked where they searched for health-related information, how
      they qualified the value of different sources, and their preferences regarding
      online communication with health care providers. Results were weighed for the
      Dutch population based on gender, age, and level of education using official
      statistics. Numbers and percentages or means and standard deviations were
      presented for different subgroups. One-way ANOVA was used to test for statistical
      differences. RESULTS: The survey was completed by 635 respondents. The Internet
      was found to be the number one source for health-related information (82.7%),
      closely followed by information provided by health care professionals (71.1%).
      Approximately one-third (32.3%) of the Dutch population search for ratings of
      health care providers. The most popular information topics were side effects of
      medication (62.5%) and symptoms (59.7%). Approximately one-quarter of the Dutch
      population prefer to communicate with a health care provider via social media
      (25.4%), and 21.2% would like to communicate via a webcam. CONCLUSIONS: The
      Internet is the main source of health-related information for the Dutch
      population. One in 4 persons wants to communicate with their physician via social
      media channels and it is expected that this number will further increase. Health
      care providers should explore new ways of communicating online and should
      facilitate ways for patients to connect with them. Future research should aim at
      comparing different patient groups and diseases, describing best practices, and
      determining cost-effectiveness.

PMID- 24088274
TI  - Obstructive sleep apnea and hypertension.

PMID- 24088273
TI  - Association of blood pressure with development of metabolic syndrome components:
      a five-year Retrospective Cohort study in Beijing.
AB  - BACKGROUND: Raised blood pressure (BP) is associated with the incidence of
      metabolic syndrome (MetS). It is unknown if subjects with different BP levels may
      develop certain components of MetS over time. We investigated the incidence of
      MetS relative to different levels of BP over a 5-year period in a Chinese
      population in Tongren Hospital, Beijing. METHODS: During the period of 2006-2011,
      we recruited 2,781 participants with no MetS, or self-reported type 2 diabetes,
      dyslipidemia, hypertension, or cardiovascular disease at baseline. Association
      rule was used to identify the transitions of MetS components over time. RESULTS:
      The incidence of MetS at follow-up was 9.74% for men and 3.21% for women in the
      group with optimal BP; 10.29% and 7.22%, respectively, in the group with normal
      BP; 10.49% and 10.84%, respectively, in the group with high-normal BP; and 14.48%
      and 23.21%, respectively in the group with high BP. The most common transition
      was from healthy to healthy in the groups with optimal or normal BP (17.9-49.3%),
      whereas in the high-normal BP group, 16.9-22.1% of subjects with raised BP
      returned to healthy status or stayed unchanged, while 13.8-21.4% of people with
      high BP tended to develop raised fasting glucose levels. CONCLUSIONS: The
      incidence of MetS increased in parallel with the increase in BP. People with
      optimal and normal BP levels were less susceptible to developing MetS over time,
      whereas abnormal BP seemed to be a pre-existing phase of MetS. High-normal BP was
      a crucial status for MetS prevention.

PMID- 24088275
TI  - JNC 8 transmogrified.

PMID- 24088276
TI  - Identifiable hypertension: a new spectrum.
AB  - Identifiable hypertension now encompasses a large and growing spectrum of
      disorders from the most common associations (eg, diabetes), to rare genetic
      disorders and adverse reactions (eg, hypertension caused by anti- VEGF cancer
      therapy). Each of these disorders requires strategies for diagnosis and
      management that extend well beyond the usual treatment of hypertension for
      maximal benefit in preventing cardiovascular disease.

PMID- 24088277
TI  - Should target organ damage become a therapeutic target?

PMID- 24088278
TI  - Increased aortic stiffness and related factors in patients with peripheral
      arterial disease.
AB  - A number of conditions have been associated with functional changes of large
      arteries. The aim of this study was to evaluate the factors associated with
      aortic stiffness in patients with peripheral arterial disease (PAD). The authors
      studied 86 patients with PAD (ankle-brachial pressure index [ABPI] <=0.9) and 86
      controls. Aortic stiffness was determined by pulse wave velocity (aPWV) using
      applanation tonometry. In PAD patients, aPWV was higher compared with controls
      (11 +/- 3 vs 9.8 +/- 1.8; P=.002). In multiple regression analysis, aPWV was
      independently associated with pulse pressure (beta=0.05, P=.01) in the PAD
      patients and with age in the control group (beta=0.08, P=.0005). The results of
      this study confirm an aPWV increase in patients with PAD and emphasize the
      association between blood pressure and aPWV. Further studies are necessary to
      assess whether higher aortic stiffening adds prognostic value to ABPI, which is
      the most powerful prognostic indicator in PAD.

PMID- 24088279
TI  - Blood pressure reclassification in adolescents based on repeat clinic blood
      pressure measurements.
AB  - The common assumption is that blood pressure (BP) will decrease on subsequent
      readings. The objective of this study is to examine the prevalence and direction
      of BP classification change with repeat measurements and compare common clinical
      characteristics of groups of patients who do and do not have a change in BP
      classification. A nationally representative subsample of 1725 adolescents aged 13
      to 18 years from the National Health and Nutrition Survey were analyzed. Three BP
      measurements were obtained. Patients were classified based on the first and the
      average of 3 BP measurements as having normal BP, hypertension, and/or
      prehypertension. Of the 1725 adolescents, 1569 (90.9%) maintained BP
      classification, 107 (6.2%) had a reduction in their classification, and 49 (2.9%)
      had an increase in their classification. Comparing the two groups that changed BP
      classification to the group without change, C-reactive protein and body mass
      index (BMI) z score were significantly higher in the groups that had a change in
      BP classification (P=.02 and <.001, respectively). After adjusting for other
      variables, higher BMI value was significantly associated with change in BP
      classification. With repeat measurements, the majority (~91%) did not have a
      change in classification. Obesity was a significant predictor of the 9% that had
      a change in classification. Repeat BP measurements in obese adolescents may lead
      to more accurate classification of BP status.

PMID- 24088280
TI  - Blood pressure control in a hypertension telemedicine intervention: does distance
      to primary care matter?
AB  - Although telemedicine may help overcome geographic access barriers, it is unknown
      whether rural patients receive greater benefits. In a secondary analysis of 503
      veterans participating in a hypertension telemedicine study, the authors
      hypothesized that patients with greater travel distances would have greater
      improvements in 18-month systolic blood pressure (SBP). Patients were categorized
      by telemedicine exposure and travel distance to primary care, derived from zip
      codes. Comparisons were (1) usual care (UC), distance <30 miles (reference); (2)
      UC, distance >=30 miles; (3) telemedicine, distance <30 miles; (4) telemedicine,
      distance >=30 miles. Compared with patients receiving UC, distance <30 miles
      (intercept=127.7), no difference in 18-month SBP was observed in patients
      receiving UC, distance >=30 miles (0.13 mm Hg, 95% confidence interval [-6.6 to
      6.8]); telemedicine, distance <30 miles (-1.1 mm Hg [-7.3 to 5.2]); telemedicine,
      distance >=30 miles (-0.80 mm Hg [-6.6 to 5.1]). Although telemedicine may help
      overcome geographic access barriers, additional studies are needed to identify
      patients most likely to benefit.

PMID- 24088281
TI  - High-sensitivity cardiac troponin T predicts nondipper hypertension in newly
      diagnosed hypertensive patients.
AB  - The increased prognostic accuracy of the high-sensitivity cardiac troponin T (hs
      cTnT) assay vs the conventional cTnT assay has recently been reported in
      hypertensive patients. The authors aimed to investigate the significance of serum
      hs-cTnT marker for prediction of nondipper hypertension (HTN) in hypertensive
      patients. A total of 317 patients with newly diagnosed HTN were studied. The
      patients were divided into two groups: 198 dipper hypertensive patients (mean
      age, 51.7 +/- 5.1 years) and 119 nondipper hypertensive patients (mean age, 53.4
      +/- 7.6 years). Hs-cTnT and N-terminal pro-brain natriuretic peptide (NT-proBNP)
      were measured in all patients. hs-cTnT and NT-proBNP were independent predictors
      for nondipper HTN (P<.05 for all). The cutoff value of hs-cTnT obtained by the
      receiver operator curve analysis was 7.55 ng/L for the prediction of nondipper
      HTN (sensitivity: 79%, specificity: 70%; 95% confidence interval, 0.769-0.860;
      P<.001). In patients with HTN, higher serum concentration of hs-cTnT even within
      normal range is an independent predictor of nondipper HTN.

PMID- 24088282
TI  - Has admission blood pressure any prognostic value in patients with subarachnoid
      hemorrhage: an emergency department experience.
AB  - Hypertension is a well-known risk factor for the development and rupture of
      cerebral aneurysms. The authors conducted a study to investigate the prognostic
      value of admission blood pressure (BP) on prognosis in patients with subarachnoid
      hemorrhage (SAH). Two hundred patients with SAH were divided into two groups
      according to Hunt Hess score (good prognosis: 1 to 3, and poor prognosis: 4 and
      5) and according to death in hospital (surveyed and died). The prognostic factors
      of SAH and BP changes according to Hunt Hess scores in the acute stages of the
      event were evaluated. Admission mean arterial BP values of the patients who died
      in hospital were significantly lower than in the patients who were surveyed
      (P=.026). The admission mean arterial BP values were found to be lower in the
      poor prognostic patients (Hunt Hess score of 4 and 5) (P<.001). Decreased
      admission BP values were found to be associated with poor prognosis and
      mortality. 

PMID- 24088283
TI  - Assessment of target organ damage in the evaluation and follow-up of hypertensive
      patients: where do we stand?
AB  - Hypertension is associated with damage to the heart, kidneys, and vascular tree.
      Assessment of target organ damage (TOD) allows better prediction of
      cardiovascular risk than conventional risk assessment. Regression of TOD during
      antihypertensive treatment, which depends on the blood pressure (BP) reduction
      and the specific ancillary properties of each drug, may indirectly indicate that
      BP is well controlled. It is unclear whether regression of TOD during treatment
      is associated with favorable outcome and should be used as a surrogate endpoint.
      There is evidence that regression of left ventricular hypertrophy and albuminuria
      are associated with a favorable outcome. However, recent studies cast doubts on
      this evidence. Thus, assessment of TOD is important to define cardiovascular
      risk, but, so far, regression of TOD cannot be regarded as a major surrogate
      therapeutic target. The present paper will provide a critical overview of the
      data available in the literature. 

PMID- 24088284
TI  - The new hypertension guidelines.
AB  - The Canadian Hypertension Education Program (CHEP) has published guidelines
      annually since 2000. The CHEP guidelines are a model of concise, comprehensive,
      up-to-date, evidence-rated guidelines for physicians who diagnose and treat
      hypertension. The guidelines address measurement of blood pressure and the
      definition of hypertension, secondary hypertension evaluation and treatment, and
      blood pressure targets and medication choices in patients with and without
      compelling indications. This review describes CHEP's process for developing
      guidelines and provides an overview of the 2013 recommendations. 

PMID- 24088285
TI  - Nutrition and nutraceutical supplements for the treatment of hypertension: part
      I.
AB  - Vascular biology, endothelial and vascular smooth muscle, and cardiac dysfunction
      play a primary role in the initiation and perpetuation of hypertension,
      cardiovascular disease, and target organ damage. Nutrient-gene interactions and
      epigenetics are predominant factors in promoting beneficial or detrimental
      effects in cardiovascular health and hypertension. Macronutrients and
      micronutrients may be able to prevent, control, or treat hypertension through
      numerous mechanisms related to vascular biology or other mechanisms. Oxidative
      stress, inflammation, and autoimmune dysfunction are some of the primary factors
      that initiate and propagate hypertension and cardiovascular disease. The
      literature suggests that there may be a complementary role of single and
      component nutraceutical supplements, vitamins, antioxidants, and minerals in the
      treatment of hypertension when combined with optimal nutrition and other
      lifestyle modifications. However, many of these studies are small and do not have
      long-term follow-up for efficacy and safety. The role of these nutrition and
      nutraceutical supplements will require careful review and additional studies to
      determine their exact role in the management of hypertension. 

PMID- 24088286
TI  - Critique of re-analysis of the TROPHY study.

PMID- 24088287
TI  - What did the great master Bach die from?

PMID- 24088288
TI  - Captopril may influence tone of human oviduct ampulla.

PMID- 24088291
TI  - PPP1CC2 can form a kinase/phosphatase complex with the testis-specific proteins
      TSSK1 and TSKS in the mouse testis.
AB  - The mouse protein phosphatase gene Ppp1cc is essential for male fertility, with
      mutants displaying a failure in spermatogenesis including a widespread loss of
      post-meiotic germ cells and abnormalities in the mitochondrial sheath. This
      phenotype is hypothesized to be responsible for the loss of the testis-specific
      isoform PPP1CC2. To identify PPP1CC2-interacting proteins with a function in
      spermatogenesis, we carried out GST pull-down assays in mouse testis lysates.
      Amongst the identified candidate interactors was the testis-specific protein
      kinase TSSK1, which is also essential for male fertility. Subsequent interaction
      experiments confirmed the capability of PPP1CC2 to form a complex with TSSK1
      mediated by the direct interaction of each with the kinase substrate protein
      TSKS. Interaction between PPP1CC2 and TSKS is mediated through an RVxF docking
      motif on the TSKS surface. Phosphoproteomic analysis of the mouse testis
      identified a novel serine phosphorylation site within the TSKS RVxF motif that
      appears to negatively regulate binding to PPP1CC2. Immunohistochemical analysis
      of TSSK1 and TSKS in the Ppp1cc mutant testis showed reduced accumulation to
      distinct cytoplasmic foci and other abnormalities in their distribution
      consistent with the loss of germ cells and seminiferous tubule disorganization
      observed in the Ppp1cc mutant phenotype. A comparison of Ppp1cc and Tssk1/2
      knockout phenotypes via electron microscopy revealed similar abnormalities in the
      morphology of the mitochondrial sheath. These data demonstrate a novel
      kinase/phosphatase complex in the testis that could play a critical role in the
      completion of spermatogenesis. 

PMID- 24088289
TI  - Zinc inhibits osteoclast differentiation by suppression of Ca2+-Calcineurin
      NFATc1 signaling pathway.
AB  - BACKGROUND: Zinc, an essential trace element, inhibits osteoclast differentiation
      in vitro and in vivo. The molecular mechanism for the inhibitory effect of zinc,
      however, is poorly understood. The purpose of this study was to investigate the
      effect of zinc and determine its molecular mechanism on receptor activator of NF
      kappaB ligand (RANKL)-induced osteoclastogenesis in mouse bone marrow-derived
      monocyte cells (BMMs) and RAW264.7 cells. RESULTS: In BMMs, zinc treatment during
      osteoclast differentiation decreased RANKL-induced osteoclast formation in a dose
      dependent manner. We show that zinc suppressed the mRNA levels of nuclear factor
      of activated T-cells, cytoplasmic 1 (Nfatc1). Zinc also accumulated phospho
      Nfatc1 (p-Nfatc1) in the cytosol in a dose-dependent manner and inhibited the
      translocation of Nfatc1 to the nucleus in RAW264.7 cells. Zinc suppressed the
      activities of Nfatc1 in the nucleus without changing the activities of NF-kappaB
      in RAW264.7 cells. In contrast, calcineurin activity decreased in response to
      zinc but its protein level was unchanged. RANKL-induced Ca2+ oscillations were
      inhibited by zinc treatment, but phospho-phospholipase Cgamma1 (p-PLCgamma1), the
      upstream signaling molecule of Ca2+ oscillations, was unaffected. Moreover, a
      constitutively active form of Nfatc1 obviously rescued suppression of
      osteoclastogenesis by zinc. CONCLUSIONS: Taken together, these results
      demonstrate for the first time that the inhibitory effect of zinc during
      osteoclastogesis is caused by suppressing the Ca2+-Calcineurin-NFATc1 signaling
      pathway. Thus, zinc may be a useful therapeutic candidate for the prevention of
      bone loss caused by NFATc1 activation in osteoclasts.

PMID- 24088292
TI  - Physiological and performance responses to a training camp in the heat in
      professional Australian football players.
AB  - PURPOSE: To examine the physiological and performance responses to a heat
      acclimatization camp in highly trained professional team-sport athletes. METHODS:
      Eighteen male Australian Rules Football players trained for 2 wk in hot ambient
      conditions (31-33 degrees C, humidity 34-50%). Players performed a laboratory
      based heat-response test (24-min walk + 24 min seated; 44 degrees C), a YoYo
      Intermittent Recovery Level 2 Test (YoYoIR2; indoor, temperate environment, 23
      degrees C) and standardized training drills (STD; outdoor, hot environment, 32
      degrees C) at the beginning and end of the camp. RESULTS: The heat-response test
      showed partial heat acclimatization (eg, a decrease in skin temperature, heart
      rate, and sweat sodium concentration, P < .05). In addition, plasma volume (PV,
      CO rebreathing, +2.68 [0.83; 4.53] mL/kg) and distance covered during both the
      YoYoIR2 (+311 [260; 361] m) and the STD (+45.6 [13.9; 77.4] m) increased postcamp
      (P < .01). None of the performance changes showed clear correlations with PV
      changes (r < .24), but the improvements in running STD distance in hot
      environment were correlated with changes in hematocrit during the heat-response
      test (r = -.52, 90%CI [-.77; -.12]). There was no clear correlation between the
      performance improvements in temperate and hot ambient conditions (r < .26).
      CONCLUSION: Running performance in both hot and temperate environments was
      improved after a football training camp in hot ambient conditions that stimulated
      heat acclimatization. However, physiological and performance responses were
      highly individual, and the absence of correlations between physical-performance
      improvements in hot and temperate environments suggests that their physiological
      basis might differ.

PMID- 24088293
TI  - Ten-year experience with extended criteria cardiac transplantation.
AB  - BACKGROUND: Extended criteria cardiac transplant (ECCT) programs expand the
      transplant pool by matching donors and recipients typically excluded from the
      transplant process because of age or comorbidity. There is a paucity of data
      examining long-term outcomes with this strategy. METHODS AND RESULTS: Between
      January 2000 and December 2009, adult patients undergoing isolated heart
      transplant were prospectively classified as ECCT based on prespecified criteria.
      Baseline characteristics and outcomes were compared between ECCT and standard
      criteria cardiac transplant recipients. Two Cox proportional hazards models were
      developed. The first to identify clinical variables contributing to survival
      between the 2 groups, and the second to determine the additional risk associated
      with assignment to ECCT. Among the 454 patients who underwent heart transplant,
      84 (18.5%) were ECCT. Compared with the patients who underwent standard criteria
      cardiac transplant, ECCT patients were older (median, 66.6 years versus 53.2
      years; P<0.001), with higher frequency of diabetes mellitus (46.4% versus 24.6%;
      P<0.001) and chronic kidney disease (median estimated glomerular filtration rate,
      55 versus 61.6 mL/min; P=0.001). After adjustment for baseline characteristics,
      standard criteria cardiac transplant survival was higher than ECCT at 1 (89%
      versus 86%; P=0.18) and 5 (77% versus 66%; P=0.035) years. In a multivariate
      model that included listing criteria, creatinine (hazard ratio, 1.05 per 0.1
      mg/dL; 95% confidence interval, 1.02-1.09; P=0.001) was a significant predictor
      of post-transplant mortality. CONCLUSIONS: ECCT is an acceptable alternative for
      advanced heart failure therapy in select patients. Age and renal dysfunction are
      important determinants of long-term survival and post-transplant morbidity.

PMID- 24088294
TI  - Biomechanical comparison of three stand-alone lumbar cages--a three-dimensional
      finite element analysis.
AB  - BACKGROUND: For anterior lumbar interbody fusion (ALIF), stand-alone cages can be
      supplemented with vertebral plate, locking screws, or threaded cylinder to avoid
      the use of posterior fixation. Intuitively, the plate, screw, and cylinder aim to
      be embedded into the vertebral bodies to effectively immobilize the cage itself.
      The kinematic and mechanical effects of these integrated components on the lumbar
      construct have not been extensively studied. A nonlinearly lumbar finite-element
      model was developed and validated to investigate the biomechanical differences
      between three stand-alone (Latero, SynFix, and Stabilis) and SynCage-Open plus
      transpedicular fixation. All four cages were instrumented at the L3-4 level.
      METHODS: The lumbar models were subjected to the follower load along the lumbar
      column and the moment at the lumbar top to produce flexion (FL), extension (EX),
      left/right lateral bending (LLB, RLB), and left/right axial rotation (LAR, RAR).
      A 10 Nm moment was applied to obtain the six physiological motions in all models.
      The comparison indices included disc range of motion (ROM), facet contact force,
      and stresses of the annulus and implants. RESULTS: At the surgical level, the
      SynCage-open model supplemented with transpedicular fixation decreased ROM (>76%)
      greatly; while the SynFix model decreased ROM 56-72%, the Latero model decreased
      ROM 36-91%, in all motions as compared with the INT model. However, the Stabilis
      model decreased ROM slightly in extension (11%), lateral bending (21%), and axial
      rotation (34%). At the adjacent levels, there were no obvious differences in ROM
      and annulus stress among all instrumented models. CONCLUSIONS: ALIF
      instrumentation with the Latero or SynFix cage provides an acceptable stability
      for clinical use without the requirement of additional posterior fixation.
      However, the Stabilis cage is not favored in extension and lateral bending
      because of insufficient stabilization.

PMID- 24088295
TI  - Is it worthwhile to conduct a randomized controlled trial of glaucoma screening
      in the United Kingdom?
AB  - OBJECTIVES: To assess the value of conducting a glaucoma screening randomized
      controlled trial in the UK. METHODS: Decision model based economic evaluation and
      value of information analysis. Model derived from a previous health technology
      assessment. Model updated in terms of structure and parameter estimates with data
      from surveys, interviews with members of the public and health care providers and
      routine sources. RESULTS: On average, across a range of ages of initiating
      screening (40-60 years), glaucoma prevalence (1-5%), screening uptake (30-100%),
      and the performance of current case finding, screening was not cost-effective at
      a L30,000 threshold per quality adjusted life year (QALY) from the perspective of
      the National Health Service (NHS). The societal value of removing all uncertainty
      around glaucoma screening is L107 million at a threshold of L20,000 per QALY. For
      informing policy decisions on glaucoma screening, reducing uncertainty
      surrounding the NHS and personal social care cost of sight impairment (L74
      million) was of most value, followed by reducing uncertainty in test performance
      (L14 million) and uptake of either screening or current eye care (L8 million
      each). CONCLUSIONS: A glaucoma screening trial in the UK is unlikely to be the
      best use of research resources. Further research to quantify the costs of sight
      impairment falling on the NHS and personal social services is a priority. Further
      development of glaucoma tests and research into strategies to promote the uptake
      of screening or current eye care such as through the use of a behavioural
      intervention would be worthwhile.

PMID- 24088296
TI  - Gene expression profiling and expanded immunohistochemistry tests to guide the
      use of adjuvant chemotherapy in breast cancer management: a systematic review and
      cost-effectiveness analysis.
AB  - BACKGROUND: Gene expression profiling (GEP) and expanded immunohistochemistry
      (IHC) tests aim to improve decision-making relating to adjuvant chemotherapy for
      women with early breast cancer. OBJECTIVE: The aim of this report is to assess
      the clinical effectiveness and cost-effectiveness of nine GEP and expanded IHC
      tests compared with current prognostic tools in guiding the use of adjuvant
      chemotherapy in patients with early breast cancer in England and Wales. The nine
      tests are BluePrint, Breast Cancer Index (BCI), IHC4, MammaPrint, Mammostrat, NPI
      plus (NPI+), OncotypeDX, PAM50 and Randox Breast Cancer Array. DATA SOURCES:
      Databases searched included MEDLINE, MEDLINE In-Process & Other Non-Indexed
      Citations, EMBASE and The Cochrane Library. Databases were searched from January
      2009 to May 2011 for the OncotypeDX and MammaPrint tests and from January 2002 to
      May 2011 for the other tests. REVIEW METHODS: A systematic review of the evidence
      on clinical effectiveness (analytical validity, clinical validity and clinical
      utility) and cost-effectiveness was conducted. An economic model was developed to
      evaluate the cost-effectiveness of adjuvant chemotherapy treatment guided by four
      of the nine test (OncotypeDX, IHC4, MammaPrint and Mammostrat) compared with
      current clinical practice in England and Wales, using clinicopathological
      parameters, in women with oestrogen receptor-positive (ER+), lymph node-negative
      (LN-), human epidermal growth factor receptor type 2-negative (HER2-) early
      breast cancer. RESULTS: The literature searches for clinical effectiveness
      identified 5993 citations, of which 32 full-text papers or abstracts (30 studies)
      satisfied the criteria for the effectiveness review. A narrative synthesis was
      performed. Evidence for OncotypeDX supported the prognostic capability of the
      test. There was some evidence on the impact of the test on decision-making and to
      support the case that OncotypeDX predicts chemotherapy benefit; however, few
      studies were UK based and limitations in relation to study design were
      identified. Evidence for MammaPrint demonstrated that the test score was a strong
      independent prognostic factor, but the evidence is non-UK based and is based on
      small sample sizes. Evidence on the Mammostrat test showed that the test was an
      independent prognostic tool for women with ER+, tamoxifen-treated breast cancer.
      The three studies appeared to be of reasonable quality and provided data from a
      UK setting (one study). One large study reported on clinical validity of the IHC4
      test, with IHC4 score a highly significant predictor of distant recurrence. This
      study included data from a UK setting and appeared to be of reasonable quality.
      Evidence for the remaining five tests (PAM50, NPI+, BCI, BluePrint and Randox)
      was limited. The economic analysis suggests that treatment guided using IHC4 has
      the greatest potential to be cost-effective at a L20,000 threshold, given the low
      cost of the test; however, further research is needed on the analytical validity
      and clinical utility of IHC4, and the exact cost of the test needs to be
      confirmed. Current limitations in the evidence base produce significant
      uncertainty in the results. OncotypeDX has a more robust evidence base, but
      further evidence on its impact on decision-making in the UK and the predictive
      ability of the test in an ER+, LN-, HER- population receiving current drug
      regimens is needed. For MammaPrint and Mammostrat there were significant gaps in
      the available evidence and the estimates of cost-effectiveness produced were not
      considered to be robust by the External Assessment Group. LIMITATIONS:
      Methodological weaknesses in the clinical evidence base relate to heterogeneity
      of patient cohorts and issues arising from the retrospective nature of the
      evidence. Further evidence is required on the clinical utility of all of the
      tests and on UK-based populations. A key area of uncertainty relates to whether
      the tests provide prognostic or predictive ability. CONCLUSIONS: The clinical
      evidence base for OncotypeDX is considered to be the most robust. The economic
      analysis suggested that treatment guided using IHC4 has the most potential to be
      cost-effective at a threshold of L20,000; however, the evidence base to support
      IHC4 needs significant further research. STUDY REGISTRATION: PROSPERO
      2011:CRD42011001361, available from
      www.crd.york.ac.uk/PROSPERO/display_record.asp?ID=CRD42011001361.

PMID- 24088298
TI  - Effectiveness of visual inspection compared with non-microbiologic methods to
      determine the thoroughness of post-discharge cleaning.
AB  - BACKGROUND: Published data to date have provided a limited comparison between non
      microbiologic methods-particularly visual inspection-and a microbiologic
      comparator to evaluate the effectiveness of environmental cleaning of patient
      rooms. We sought to compare the accuracy of visual inspection with other non
      microbiologic methods of assessing the effectiveness of post-discharge cleaning
      (PDC). METHODS: Prospective evaluation to determine the effectiveness of PDC in
      comparison to a microbiologic comparator. Using a highly standardized methodology
      examining 15 high-touch surfaces, the effectiveness of PDC was evaluated by
      visual inspection, the removal of fluorescent marker (FM) placed prior to room
      occupancy, quantification of adenosine triphosphate (ATP) levels, and culture for
      aerobic colony counts (ACC). RESULTS: Twenty rooms including 293 surfaces were
      sampled in the study, including 290 surfaces sampled by all four methods. ACC
      demonstrated 72% of surfaces to be microbiologically clean. Visual inspection,
      FM, ATP demonstrated 57%, 49%, and 66% of surfaces to be clean. Using ACC as a
      microbiologic comparator, the sensitivity of visual inspection, FM, and ATP to
      detect a clean surface were 60%, 51%, and 70%, respectively; the specificity of
      visual inspection, FM, and ATP were 52%, 56%, and 44%. CONCLUSIONS: In assessing
      the effectiveness of PDC, there was poor correlation between the two most
      frequently studied commercial methods and a microbiologic comparator. Visual
      inspection performed at least as well as commercial methods, directly addresses
      patient perception of cleanliness, and is economical to implement.

PMID- 24088297
TI  - Impact of botanical oils on polyunsaturated fatty acid metabolism and leukotriene
      generation in mild asthmatics.
AB  - BACKGROUND: Dietary supplementation with botanical oils that contain n-6 and n-3
      eighteen carbon chain (18C)-PUFA such as gamma linolenic acid (GLA, 18:3n-6),
      stearidonic acid (SDA, 18:4n-3) and alpha linolenic acid (ALA, 18:3n-3) have been
      shown to impact PUFA metabolism, alter inflammatory processes including
      arachidonic acid (AA) metabolism and improve inflammatory disorders. METHODS: The
      diet of mild asthmatics patients was supplemented for three weeks with varying
      doses of two botanical seed oils (borage oil [Borago officinalis, BO] and echium
      seed oil [Echium plantagineum; EO]) that contain SDA, ALA and GLA. A three week
      wash out period followed. The impact of these dietary manipulations was evaluated
      for several biochemical endpoints, including in vivo PUFA metabolism and ex vivo
      leukotriene generation from stimulated leukocytes. RESULTS: Supplementation with
      several EO/BO combinations increased circulating 20-22 carbon (20-22C) PUFAs,
      including eicosapentaenoic acid (EPA), docosapentaenoic acid (DPA), and dihommo
      gammalinolenic acid (DGLA), which have been shown to inhibit AA metabolism and
      inflammation without impacting circulating AA levels. BO/EO combinations also
      inhibited ex vivo leukotriene generation with some combinations attenuating
      cysteinyl leukotriene generation in stimulated basophils by >50% and in
      stimulated neutrophils by >35%. CONCLUSIONS: This study shows that dietary
      supplementation with BO/EO alters 20-22C PUFA levels and attenuates leukotriene
      production in a manner consistent with a reduction in inflammation.

PMID- 24088299
TI  - Probabilistic model for individual assessment of central hyperexcitability using
      the nociceptive withdrawal reflex: a biomarker for chronic low back and neck
      pain.
AB  - BACKGROUND: The nociceptive withdrawal reflex (NWR) has been proven to be a
      valuable tool in the objective assessment of central hyperexcitability in the
      nociceptive system at spinal level that is present in some chronic pain
      disorders, particularly chronic low back and neck pain. However, most of the
      studies on objective assessment of central hyperexcitability focus on population
      differences between patients and healthy individuals and do not provide tools for
      individual assessment. In this study, a prediction model was developed to
      objectively assess central hyperexcitability in individuals. The method is based
      on statistical properties of the EMG signals associated with the nociceptive
      withdrawal reflex. The model also supports individualized assessment of patients,
      including an estimation of the confidence of the predicted result. RESULTS: up to
      80% classification rates were achieved when differentiating between healthy
      volunteers and chronic low back and neck pain patients. EMG signals recorded
      after stimulation of the anterolateral and heel regions and of the sole of the
      foot presented the best prediction rates. CONCLUSIONS: A prediction model was
      proposed and successfully tested as a new approach for objective assessment of
      central hyperexcitability in the nociceptive system, based on statistical
      properties of EMG signals recorded after eliciting the NWR. Therefore, the
      present statistical prediction model constitutes a first step towards potential
      applications in clinical practice.

PMID- 24088300
TI  - Strengthening capacity for AIDS vaccine research: analysis of the Pfizer Global
      Health Fellows program and the International AIDS Vaccine Initiative.
AB  - BACKGROUND: Industry partnerships can help leverage resources to advance HIV/AIDS
      vaccine research, service delivery, and policy advocacy goals. This often
      involves capacity building for international and local non-governmental
      organizations (NGOs). International volunteering is increasingly being used as a
      capacity building strategy, yet little is known about how corporate volunteers
      help to improve performance of NGOs in the fight against HIV/AIDS. METHODS: This
      case study helps to extend our understanding by analyzing how the Pfizer Global
      Health Fellows (GHF) program helped develop capacity of the International AIDS
      Vaccine Initiative (IAVI), looking specifically at Fellowship activities in South
      Africa, Kenya, and Uganda. From 2005-2009, 8 Pfizer GHF worked with IAVI and
      local research centers to strengthen capacity to conduct and monitor vaccine
      trials to meet international standards and expand trial activities. Data
      collection for the case study included review of Fellow job descriptions, online
      journals, evaluation reports, and interviews with Fellows and IAVI staff.
      Qualitative methods were used to analyze factors which influenced the process and
      outcomes of capacity strengthening. RESULTS: Fellows filled critical short-term
      expert staffing needs at IAVI as well as providing technical assistance and staff
      development activities. Capacity building included assistance in establishing
      operating procedures for the start-up period of research centers; training staff
      in Good Clinical Practice (GCP); developing monitoring capacity (staff and
      systems) to assure that centers are audit-ready at all times; and strategic
      planning for data management systems. Factors key to the success of volunteering
      partnerships included similarities in mission between the corporate and NGO
      partners, expertise and experience of Fellows, and attitudes of partner
      organization staff. CONCLUSION: By developing standard operating procedures,
      ensuring that monitoring and regulatory compliance systems were in place,
      training African investigators and community members, and engaging in other
      systems strengthening activities, the GHF program helped IAVI to accelerate
      vaccine development activities in the field, and to develop the organization's
      capacity to manage change in the future. Our study suggests that a program of
      sustained corporate volunteering over several years may increase organizational
      learning and trust, leading to stronger capacity to advance and achieve NGO
      goals.

PMID- 24088301
TI  - ScreenSifter: analysis and visualization of RNAi screening data.
AB  - BACKGROUND: RNAi screening is a powerful method to study the genetics of
      intracellular processes in metazoans. Technically, the approach has been largely
      inspired by techniques and tools developed for compound screening, including
      those for data analysis. However, by contrast with compounds, RNAi inducing
      agents can be linked to a large body of gene-centric, publically available data.
      However, the currently available software applications to analyze RNAi screen
      data usually lack the ability to visualize associated gene information in an
      interactive fashion. RESULTS: Here, we present ScreenSifter, an open-source
      desktop application developed to facilitate storing, statistical analysis and
      rapid and intuitive biological data mining of RNAi screening datasets. The
      interface facilitates meta-data acquisition and long-term safe-storage, while the
      graphical user interface helps the definition of a hit list and the visualization
      of biological modules among the hits, through Gene Ontology and protein-protein
      interaction analyses. The application also allows the visualization of screen-to
      screen comparisons. CONCLUSIONS: Our software package, ScreenSifter, can
      accelerate and facilitate screen data analysis and enable discovery by providing
      unique biological data visualization capabilities.

PMID- 24088302
TI  - Associations between risk perception, spontaneous adaptation behavior to heat
      waves and heatstroke in Guangdong province, China.
AB  - BACKGROUND: In many parts of the world, including in China, extreme heat events
      or heat waves are likely to increase in intensity, frequency, and duration in
      light of climate change in the next decades. Risk perception and adaptation
      behaviors are two important components in reducing the health impacts of heat
      waves, but little is known about their relationships in China. This study aimed
      to examine the associations between risk perception to heat waves, adaptation
      behaviors, and heatstroke among the public in Guangdong province, China. METHODS:
      A total of 2,183 adult participants were selected using a four-stage sampling
      method in Guangdong province. From September to November of 2010 each subject was
      interviewed at home by a well-trained investigator using a structured
      questionnaire. The information collected included socio-demographic
      characteristics, risk perception and spontaneous adaptation behaviors during heat
      wave periods, and heatstroke experience in the last year. Chi-square tests and
      unconditional logistic regression models were employed to analyze the data.
      RESULTS: This study found that 14.8%, 65.3% and 19.9% of participants perceived
      heat waves as a low, moderate or high health risk, respectively. About 99.1%
      participants employed at least one spontaneous adaptation behavior, and 26.2%,
      51.2% and 22.6% respondents employed <4, 4-7, and >7 adaptation behaviors during
      heat waves, respectively. Individuals with moderate (OR=2.93, 95% CI: 1.38-6.22)
      or high (OR=10.58, 95% CI: 4.74-23.63) risk perception experienced more
      heatstroke in the past year than others. Drinking more water and wearing light
      clothes in urban areas, while decreasing activity as well as wearing light
      clothes in rural areas were negatively associated with heatstroke. Individuals
      with high risk perception and employing <4 adaptation behaviors during heat waves
      had the highest risks of heatstroke (OR=47.46, 95% CI: 12.82-175.73).
      CONCLUSIONS: There is a large room for improving health risk perception and
      adaptation capacity to heat waves among the public of Guangdong province. People
      with higher risk perception and fewer adaptation behaviors during heat waves may
      be more vulnerable to heat waves.

PMID- 24088303
TI  - Necessity of face-to-face encounters with recipients of cardiovascular
      implantable electronic devices with remote monitoring.

PMID- 24088304
TI  - Dilated cardiomyopathy-associated FHOD3 variant impairs the ability to induce
      activation of transcription factor serum response factor.
AB  - BACKGROUND: Dilated cardiomyopathy (DCM) is characterized by a dilated left
      ventricular cavity with systolic dysfunction manifested by heart failure. It has
      been revealed that mutations in genes for cytoskeleton or sarcomere proteins
      cause DCM. However, the disease-causing mutations can be found only in far less
      than half of patients with a family history, indicating that there should be
      other disease genes for DCM. Formin homology 2 domain containing 3 (FHOD3) is a
      sarcomeric protein expressed in the heart that plays an essential role in
      sarcomere organization during myofibrillogenesis. The purpose of this study was
      to explore a possible novel disease gene for DCM. METHODS AND RESULTS: We
      analyzed 48 Japanese familial DCM patients for mutations in FHOD3, and a missense
      variant, Tyr1249Asn, which was predicted to modify the 3D structure and damage
      protein function, was found in a case with adult-onset DCM. Functional studies
      revealed that the DCM-associated mutation significantly reduced the ability to
      induce actin dynamics-dependent activation of serum response factor, although no
      remarkable change in the cellular localization was induced in neonatal rat
      cardiomyocytes transfected with a mutant construct of FHOD3. CONCLUSIONS: The DCM
      associated FHOD3 variant may cause DCM by interfering with actin filament
      assembly.

PMID- 24088305
TI  - Assessment of pulmonary arterial pressure by velocity-encoded cine magnetic
      resonance imaging in children with congenital heart disease.
AB  - BACKGROUND: Velocity-encoded cine magnetic resonance imaging (VEC-MRI) has
      recently been reported as effective for assessing not only pulmonary blood flow
      (Qp) but also pulmonary arterial pressure (PAP) in adults. However, there have
      been few reports on the usefulness of VEC-MRI for assessing PAP in children with
      congenital heart disease (CHD). METHODS AND RESULTS: We evaluated 34 children
      with CHD. Qp and systemic blood flows (Qs) were determined by cardiac
      catheterization and VEC-MRI. The right-to-left Qp ratio (R/L) was measured by
      pulmonary perfusion scintigraphy and VEC-MRI. The pulmonary-to-systemic blood
      pressure ratio (Pp/Ps) was determined by cardiac catheterization. The
      acceleration time (AcT), ejection time (ET), peak velocity (PV), acceleration
      volume (AcV), and maximal change in flow rate during ejection (MCFR) in the
      pulmonary arteries, which were standardized by body surface area, were determined
      by VEC-MRI. The children were divided into 2 groups according to Pp/Ps. The Qs,
      R/L ratio and Qp/Qs obtained by VEC-MRI strongly correlated with those obtained
      by catheterization and scintigraphy. No significant differences in AcT, ET,
      AcT/ET, PV, or AcV were observed between the 2 groups. However, a significant
      difference was observed in MCFR. Furthermore, a significant correlation was
      observed between the MCFR and Pp/Ps. CONCLUSIONS: This study clearly demonstrated
      that VEC-MRI is useful for assessing not only blood flow, but also PAP, by
      referring to MCFR in children.

PMID- 24088307
TI  - Perforation of Meckel's diverticulum by a fish bone presenting as acute
      appendicitis: a case report.
AB  - INTRODUCTION: Meckel's diverticulum is the commonest congenital abnormality of
      the gastrointestinal tract. Most of them are asymptomatic but can rarely present
      with forms of complications such as bleeding, obstruction, diverticulitis,
      intussusception and neoplasm. Patients with a perforation of Meckel's
      diverticulum by a foreign body are rare and may present with right iliac fossa
      pain, which mimics acute appendicitis. CASE PRESENTATION: A 64-year-old Greek man
      presented with an eight-hour history of right iliac fossa pain. On examination,
      our patient had tenderness in his right iliac fossa. A provisional diagnosis of
      acute appendicitis was made. He was taken to theatre with the option of an
      appendicectomy. His appendix was found to have an about normal appearance. An
      inflamed Meckel's diverticulum that had been perforated by a fish bone was found
      to be the cause of the abdominal pain. A Meckel's diverticulectomy was performed.
      Our patient made an uneventful recovery and was discharged after two days.
      CONCLUSIONS: Complications of Meckel's diverticulum can be difficult to diagnose
      and early recognition and timely operative intervention must occur in order to
      provide the best outcome for these patients. This is an interesting and unusual
      case of perforation of Meckel's diverticulum that highlights the importance of
      considering Meckel's diverticulum as a differential diagnosis in every patient
      presenting with acute abdomen.

PMID- 24088308
TI  - 5-year survival and rehospitalization due to stroke recurrence among patients
      with hemorrhagic or ischemic strokes in Singapore.
AB  - BACKGROUND: Stroke is the 4th leading cause of death and 1st leading cause of
      disability in Singapore. However the information on long-term post stroke
      outcomes for Singaporean patients was limited. This study aimed to investigate
      the post stroke outcomes of 5-year survival and rehospitalization due to stroke
      recurrence for hemorrhagic and ischemic stroke patients in Singapore. The
      outcomes were stratified by age, ethnic group, gender and stroke types. The
      causes of death and stroke recurrence were also explored in the study. METHODS: A
      multi-site retrospective cohort study. Patients admitted for stroke at any of the
      three hospitals in the National Healthcare Group of Singapore were included in
      the study. All study patients were followed up to 5 years. Kaplan-Meier was
      applied to study the time to first event, death or rehospitalization due to
      stroke recurrence. Cox proportional hazard model was applied to study the time to
      death with adjustment for stroke type, age, sex, ethnic group, and admission
      year. Cumulative incidence model with competing risk was applied for comparing
      the risks of rehospitalization due to stroke recurrence with death as the
      competing risk. RESULTS: Totally 12,559 stroke patients were included in the
      study. Among them, 59.3% survived for 5 years; 18.4% were rehospitalized due to
      stroke recurrence in 5 years. The risk of stroke recurrence and mortality
      increased with age in all stroke types. Gender, ethnic group and admitting year
      were not significantly associated with the risk of mortality or stroke recurrence
      in hemorrhagic stroke. Male or Malay patient had higher risk of stroke recurrence
      and mortality in ischemic stroke. Hemorrhagic stroke had higher early mortality
      while ischemic stroke had higher recurrence and late mortality. The top cause of
      death among died stroke patients was cerebrovascular diseases, followed by
      pneumonia and ischemic heart diseases. The recurrent stroke was most likely to be
      the same type as the initial stroke among rehospitalized stroke patients.
      CONCLUSIONS: Five year post-stroke survival and rehospitalization due to stroke
      recurrence as well as their associations with patient demographics were studied
      for different stroke types in Singapore. Specific preventive strategies are
      needed to target the high risk groups to improve their long-term outcomes after
      acute stroke.

PMID- 24088309
TI  - Long-term outcome of the WallFlex partially covered stent for unresectable
      malignant biliary obstruction: a multicenter single-arm prospective study.
AB  - BACKGROUND/AIMS: Covered metallic stent was developed to prevent tumor ingrowth.
      However, procedural accidents due to its insertion often occur and migration
      after long-term insertion causes problems. The WallFlex partially covered stent
      (WF) with reduced axial force enables stenting along the bile duct. We examined
      the usefulness of WF placement in an unresectable malignant distal biliary
      obstruction. METHODOLOGY: We examined procedural accidents, stent obstruction
      rate, and patency period caused by WF insertion. RESULTS: Ninety-seven patients
      were analyzed; procedural accidents caused by WF insertion occurred in 8 patients
      (7.2%) composed of acute cholecystitis in 3 patients (3.2%), acute pancreatitis
      in 2 patients (2.1%), acute cholangitis in 1 patient (1%), and other in 1 patient
      (1%). The stent obstruction rate was 19.6% (19 patients), and obstruction cause
      includes sludge in 9 patients (9.3%), migration in 4 patients (4.1%), food
      impaction in 3 patients (3.1%), ingrowth in 1 patient (1%), overgrowth in 0
      patients (0%), and unknown in 2 patients (2.1%). The mean stent patency period
      was 634.918 +/- 66.545 (7-946) days. CONCLUSIONS: WF has less procedural
      accidents when inserted into unresectable malignant biliary obstruction patients
      with reduced migration rate after a long period and low obstruction rate.

PMID- 24088310
TI  - Second hepatectomy for recurrent hepatocellular carcinoma achieved sustained
      virological response to interferon therapy for hepatitis C.
AB  - BACKGROUND/AIMS: Interferon (IFN) improves the prognosis of HCV-related
      hepatocellular carcinoma (HCC) in patients. However, the effects of IFN therapy
      for second hepatectomy (Hx) for recurrent HCC have not been established.
      METHODOLOGY: Subjects included 96 patients who underwent a second Hx for
      recurrence of HCV-related HCC. Forty-four patients received IFN therapy past or
      postoperatively of the first Hx. Twenty of those patients attained a sustained
      viral response (SVR). The other 24 were non-responders (NR) and 52 patients who
      had not received IFN therapy (non-IFN) were classified as the NR/non-IFN group.
      RESULTS: Overall survival (SVR group vs. NR/non-IFN group: 5-yr, 91.7 vs. 51.0%;
      p = 0.012) and disease-free survival (SVR group vs. NR/non-IFN group: 3-yr, 64.7
      vs. 25.9%; p = 0.006) rates were significantly different in both groups. By
      multivariate analysis, NR/non-IFN therapy, was the independent risk factor for
      overall survival (p = 0.025) and disease-free survival (p = 0.006) after second
      Hx. CONCLUSIONS: SVR achieved past or postoperatively of the first Hx of HCV
      related HCC significantly inhibits recurrence and consequently improves patient
      survival after second Hx for recurrent HCC. Patients with SVR to IFN therapy
      would be good candidates for second Hx for recurrent HCC.

PMID- 24088311
TI  - Branched-chain amino acids to tyrosine ratio (BTR) predicts intrahepatic distant
      recurrence and survival for early hepatocellular carcinoma.
AB  - BACKGROUND/AIMS: The Child-Pugh classification system is the most widely used
      system for assessing hepatic functional reserve in HCC treatment. In the Child
      Pugh classification system, serum albumin levels are used to accurately assess
      the status of protein metabolism and nutrition. To date, a lack of attention has
      been given to amino acid metabolism. In the present study, we investigated
      whether the branched-chain amino acids to tyrosine ratio (BTR) as an indicator of
      amino acid metabolism can serve as both a prognostic factor for early HCC and a
      predictive factor for recurrence. METHODOLOGY: We conducted a cohort study of 50
      patients with stage I/II HCC enrolled between May 2002 and December 2010. It was
      investigated whether BTR can serve as both a prognostic factor and a predictive
      factor for HCC recurrence. RESULTS: Overall survival rates were significantly
      higher in patients with high baseline BTR than in those with low BTR.
      Multivariate analysis showed that both BTR and serum albumin were prognostic
      factors, and that BTR was the best predictive factor for recurrence. CONCLUSIONS:
      BTR was a prognostic factor for early HCC and the most predictive factor for
      intrahepatic distant recurrence and contributing factors for survival.

PMID- 24088306
TI  - Usefulness of combined risk stratification with heart rate and systolic blood
      pressure in the management of chronic heart failure. A report from the CHART-2
      study.
AB  - BACKGROUND: The appropriate target ranges of heart rate (HR) and systolic blood
      pressure (SBP) for the management of chronic heart failure (CHF) patients remain
      to be elucidated in a large-scale cohort study. METHODS AND RESULTS: We examined
      3,029 consecutive CHF patients with sinus rhythm (SR) (mean age, 67.9 years)
      registered in the Chronic Heart Failure Analysis and Registry in the Tohoku
      District-2 Study (CHART-2; NCT00418041). There were 357 deaths (11.8%) during the
      median follow-up of 3.1 years. We first performed the classification and
      regression tree analysis for mortality, identifying SBP <89 mmHg, HR >70
      beats/min and SBP <115 mmHg as the primary, secondary and tertiary
      discriminators, respectively. According to these, we divided the patients into
      low- (n=1,131), middle- (n=1,624) and high-risk (n=274) groups with mortality
      risk <10%, 10-20% and >20%, respectively. The low-risk group was characterized by
      SBP >115 mmHg and HR <70 beats/min and the high-risk group by SBP <89 mmHg
      regardless of HR values or SBP 89-115 mmHg and HR >76 beats/min. Multivariate Cox
      regression analysis revealed that the hazard ratio of all-cause death for low-,
      middle- and high-risk groups was 1.00 (reference), 1.48 (95% confidence interval
      (CI): 1.10-1.99, P=0.009) and 2.44 (95% CI 1.66-3.58, P<0.001), respectively.
      Subgroup analysis revealed that age >=70 years, diabetes, or reduced left
      ventricular function had higher hazard ratios in the high-risk group.
      CONCLUSIONS: The results demonstrate the usefulness of combined risk
      stratification of HR and SBP in CHF patients with SR.

PMID- 24088312
TI  - Suprahilar vascular control and stapling device transection of Glissonian pedicle
      in major and minor hepatectomies.
AB  - BACKGROUND/AIMS: In this study we analyzed our experience of suprahilar-posterior
      intrahepatic Glissonian pedicle approach using an endo-GIA vascular stapling
      device for the pedicle and hepatic vein division. METHODOLOGY: Sixty-eight 68
      major and 102 minor liver resections were performed. The hilar extrahepatic
      structures remain intact, and during parenchyma dissection by CUSA, the whole
      right or left or the appropriate segmental pedicle was isolated intrahepatically
      and then transected using a stapler device. RESULTS: The minor liver resections
      was associated with significantly shorter surgery duration (95.1 + 31.1 vs. 186.6
      +/- 56.5) and transection time (35.9 +/- 14.5 vs. 65.3 +/- 17.2) than major
      hepatectomies (p < 0.001 for all). The mean blood loss was 255.6 + 129.9 mL in
      minor resection and 385.7 + 200.1 mL in major resection (p = 0.003). The mean
      blood transfusion requirement was 300.8 + 99.5 mL for the patients with minor
      hepatectomy and 450.9 + 89.6 mL for those with major liver resection (p = 0.067).
      There was no significant difference in morbidity and mortality between the groups
      (p = 0.989; p = 0.920). Major as well as minor liver resection were a superior
      oncologic operation with no significant difference in the 3-year overall survival
      rates. CONCLUSIONS: Liver transection using CUSA with suprahilar endo-GIA
      stapling of Glisson's pedicle, as well as major hepatic veins represents an
      effective and safe surgical procedure.

PMID- 24088313
TI  - Hematological benefits after spleen-preserving distal pancreatectomy:
      perioperative and long-term outcome analysis.
AB  - BACKGROUND/AIMS: Despite the emphasis on its role, the spleen has commonly been
      removed in distal pancreatectomy. We designed this study to evaluate the efficacy
      of spleen salvage during distal pancreatectomy for patients with benign and
      borderline malignant tumors. METHODOLOGY: From January 2005 to July 2009, 82
      patients underwent distal pancreatectomy with splenectomy (DPS) and 78 patients
      underwent spleen-preserving distal pancreatectomy (SPDP). Medical records were
      retrospectively reviewed. RESULTS: The demographics and final diagnoses were
      similar between the two groups. There were no significant differences in
      estimated blood loss, intraoperative transfusion and operative time between the
      two groups. More perioperative complications occurred in DPS group than in the
      SPDP group (p = 0.0344). Consequently, postoperative hospital stay was
      significantly shorter in SPDP group than in DPS group (p = 0.0273). Platelet
      counts on postoperative day (POD) 5, hemoglobin on POD 3, WBC counts and CRP
      level on POD 2 were significantly higher in the DPS group than in the SPDP group
      and these differences continued to be significant for months after surgery.
      CONCLUSIONS: In addition to frequent higher-grade complications, prolonged
      hospital stays, DPS appeared to result in severer hematological abnormalities.
      Even an effort to preserve adult spleen in distal pancreatectomy is worthwhile.

PMID- 24088314
TI  - Retrospective evaluation of the clinical necessity of external biliary drainage
      after pancreaticoduodenectomy.
AB  - BACKGROUND/AIMS: To evaluate the efficacy of internal biliary drainage after
      pancreaticoduodenectomy (PD), postoperative gastrointestinal function and
      complications of PD were compared in patients with and without the use of an
      external drainage stent for hepaticojejunostomy (HJ). METHODOLOGY: Between June
      2005 and September 2011, 66 patients who underwent PD, including 40 patients with
      externally-stented HJ (ES group) and 26 patients with non-stented HJ (NS group),
      were included in this study, and postoperative bowel movements, oral intake, and
      complications were assessed. RESULTS: Time to tolerance of water or solid food
      were comparable between the two groups, and time to first bowel movement was
      significantly shorter in the NS group than in the ES group (3.2 +/- 1.6 days
      versus 4.6 +/- 1.7 days; p = 0.002). There were no differences in the incidence
      and severity of postoperative complications when comparing the two groups,
      whereas the incidence of postoperative cholangitis was significantly higher in
      the ES group (25.0%) than in the NS group (3.8%; p = 0.024). CONCLUSIONS:
      External biliary drainage may have a negative impact on biliary complications
      after PD, especially on the incidence of postoperative cholangitis.

PMID- 24088315
TI  - Expression of protease-activated receptor-2 in human gastric stromal tumor and
      its clinicopathological significance.
AB  - BACKGROUND/AIMS: To explore the expression of protein-activated receptor-2 (PAR
      2) in human gastric stromal tumor and its clinicopathological significance.
      METHODOLOGY: The expression of PAR-2 was detected with immunohistochemisty, RT
      PCR and Western blot in tumor tissue, peritumoral tissue and gastric normal
      tissue from 72 patients with gastric stromal tumor. RESULTS: PAR-2 expression was
      significantly higher in peritumoral tissue (p < 0.05) and tumor tissue (p < 0.01)
      than in gastric normal tissue, and significantly higher in tumor tissue than in
      peritumoral tissue (p < 0.01). With the increase in NIH grade, PAR-2 expression
      was elevated in tumor tissues. PAR-2 expression was strongly associated with
      mucosal invasion. CONCLUSIONS: PAR-2 expression is significantly higher in
      gastric stromal tumor tissue than in peritumoral tissue and gastric normal
      tissue. The high expression of PAR-2 may be associated with the invasion and
      metastasis of gastric stromal tumor.

PMID- 24088316
TI  - Scoring system for predicting recurrence after chemoradiotherapy including 5
      fluorouracil and platinum for patients with esophageal cancer.
AB  - BACKGROUND/AIMS: We have retrospectively evaluated clinical data obtained before
      therapy to enable reliable prediction of recurrence after chemoradiotherapy (CRT)
      for esophageal cancer. METHODOLOGY: We analyzed 108 patients who received 5
      fluorouracil and platinum combined with 60 Gy radiation. Of the 108 patients, 42
      patients with complete response after CRT were selected for this study. The
      endpoint was recurrence after CRT. Factors significantly related to recurrence
      were extracted by the multivariate analysis, and a recurrence score was prepared
      by combining these factors. RESULTS: The median follow-up interval was 18.5 (2
      103) months. Recurrent disease was found in 16 (38.1%) patients. In the
      univariate analysis, recurrence was associated with nutrition status, family
      history, dysphagia, location, and length of the tumor. In the multivariate
      analysis, location of the tumor was selected as a significant factor that
      contributed independently to recurrence after CRT (p < 0.05). The hazard ratios
      of the five selected factors was approximated and scored. The cumulative
      probabilities of tumor recurrence were significantly higher in the high score
      group than in the low score group (47.5% vs. 12.5% at 6 months, p < 0.01).
      CONCLUSIONS: The recurrence score is suggested to be an appropriate scoring
      system with which to predict recurrence in patients with esophageal cancer.

PMID- 24088317
TI  - One-stop shop for 3-dimensional anatomy of hepatic vasculature and bile duct with
      special reference to biliary image reconstruction.
AB  - BACKGROUND/AIMS: Three-dimensional CT has become an essential tool for successful
      hepatic surgery. Up to now, efforts have been made to simultaneously visualize
      hepatic vasculature and bile ducts. Herein, we introduce a new one-stop shop
      approach to hepatic 3D-anatomy, using a standard enhanced MDCT alone.
      METHODOLOGY: A 3D-reconstruction of hepatic vasculature was made using data from
      contrast enhanced MDCT and SYNAPSE VINCENT software. We identified bile ducts
      from axial 2D image, and then reconstructed the 3D image. Both hepatic
      vasculature and bile duct images were integrated into a single image and it was
      compared with the 3D image, utilized with MRCP or DIC-CT. RESULTS: The first
      branches of both the right and left hepatic ducts were hand-traced and visualized
      for all 100 cases. The second branches of these ducts were visualized in 69
      cases, and only the right second branch was recognized in 52 cases. Anomalous
      variations of bile ducts, such as posterior branch joining into common hepatic
      duct, were recognized in 12 cases. These biliary tract variations were all
      confirmed by MRCP or DIC-CT. CONCLUSIONS: Our new one-stop shop approach using
      the 3D imaging technique might contribute to successful hepatectomy as well as
      reduce medical costs and radiation exposure by omission of MRCP and DIC-CT.

PMID- 24088318
TI  - High intensity focused ultrasound treatment for patients with local advanced
      pancreatic cancer.
AB  - BACKGROUND/AIMS: To evaluate the safety and efficacy of high intensity focused
      ultrasound (HIFU) therapy in patients with local advanced pancreatic cancer.
      METHODOLOGY: 39 patients with local advanced pancreatic cancer were treated with
      HIFU, including 26 male and 13 female patients. The locations of the tumours were
      as follows: head of pancreas in 7 patients, body and/or tail of pancreas in 32
      patients. Pain relief, time to progression (TTP), median survival and
      complications were analysed after HIFU treatment. RESULTS: There were no severe
      complications or adverse events related to HIFU therapy in any of the patients
      treated. Pain relief was achieved in 79.5% of patients. Median TTP was 5.0
      months. The median overall survival time was 11 months. 6-month and 1-year
      survival rate for patients were 82.1% and 30.8% respectively. CONCLUSIONS:
      Although this study may have limitations, preliminary results demonstrate the
      safetyof clinical application of HIFU for pancreatic cancer and reveal it to be a
      promising mode of treatment for local advanced pancreatic cancers.

PMID- 24088320
TI  - Fluid balance, carbohydrate ingestion, and body temperature during men's stage
      race cycling in temperate environmental conditions.
AB  - PURPOSE: To observe voluntary fluid and carbohydrate intakes and thermoregulatory
      characteristics of road cyclists during 2 multiday, multiple-stage races in
      temperate conditions. METHODS: Ten internationally competitive male cyclists
      competed in 2 stage races (2009 Tour of Gippsland, T1, n = 5; 2010 Tour of
      Geelong, T2, n = 5) in temperate conditions (13.2-15.8 degrees C; 54-80% relative
      humidity). Body mass (BM) was recorded immediately before and after each stage.
      Peak gastrointestinal temperature (TGI peak) was recorded throughout each stage.
      Cyclists recalled the types and volumes of fluid and food consumed throughout
      each stage. RESULTS: Although fluid intake varied according to the race format,
      there were strong correlations between fluid intake and distance across all
      formats of racing, in both tours (r = .82, r = .92). Within a stage, the
      relationship between finishing time and fluid intake was trivial. Mean BM change
      over a stage was 1.3%, with losses >2% BM occurring on 5 out of 43 measured
      occasions and the fastest competitors incurring lower BM changes. Most subjects
      consumed carbohydrate at rates that met the new guidelines (30-60 g/h for 2-3 h,
      ~90 g/h for >3 h), based on event duration. There were consistent observations of
      TGI peak >39 degrees C during stages of T1 (67%) and T2 (73%) despite temperate
      environmental conditions. CONCLUSION: This study captured novel effects of high
      intensity stage racing in temperate environmental conditions. In these
      conditions, cyclists were generally able to find opportunities to consume fluid
      and carbohydrate to meet current guidelines. We consistently observed high TGI
      peak, which merits further investigation.

PMID- 24088321
TI  - Online drug user-led harm reduction in Hungary: a review of "Daath".
AB  - Harm reduction has been increasingly finding its way into public drug policies
      and healthcare practices worldwide, with successful intervention measures
      justifiably focussing on the highest-risk groups, such as injecting drug users.
      However, there are also other types of drug users in need for harm reduction,
      even though they pose less, low, or no public health risk. Occasionally, drug
      users may autonomously organise themselves into groups to provide advocacy, harm
      reduction, and peer-help services, sometimes online. The http://www.daath.hu
      website has been operated since 2001 by the "Hungarian Psychedelic Community", an
      unorganised drug user group with a special interest in hallucinogenic and related
      substances. As of today, the website serves about 1200 visitors daily, and the
      online community comprises of more than 8000 registered members. The Daath
      community is driven by a strong commitment to the policy of harm reduction in the
      form of various peer-help activities that aim to expand harm reduction without
      promoting drug use. Our review comprehensively summarises Daath's user-led harm
      reduction services and activities from the last ten years, firstly outlining the
      history and growth phases of Daath, along with its self-set guidelines and
      policies. Online services (such as a discussion board, and an Ecstasy pill
      database) and offline activities (such as Ecstasy pill field testing, and a
      documentary film about psychedelics) are described. In order to extend its harm
      reduction services and activities in the future, Daath has several social,
      commercial, and legislative challenges to face. Starting with a need to realign
      its focus, outlooks for the upcoming operation of Daath are pondered. Future
      trends in harm reduction, such as separating harm-decreasing from benefit
      increasing, are also discussed. We aim to share these innovative harm reduction
      measures and good practices in order to be critically assessed, and--if found
      useful--adapted and applied elsewhere.

PMID- 24088319
TI  - Prostate stereotactic body radiotherapy with simultaneous integrated boost: which
      is the best planning method?
AB  - BACKGROUND: The delivery of a simultaneous integrated boost to the intra
      prostatic tumour nodule may improve local control. The ability to deliver such
      treatments with hypofractionated SBRT was attempted using RapidArc (Varian
      Medical systems, Palo Alto, CA) and Multiplan (Accuray inc, Sunnyvale, CA).
      MATERIALS AND METHODS: 15 patients with dominant prostate nodules had RapidArc
      and Multiplan plans created using a 5 mm isotropic margin, except 3 mm
      posteriorly, aiming to deliver 47.5 Gy in 5 fractions to the boost whilst
      treating the whole prostate to 36.25 Gy in 5 fractions. An additional RapidArc
      plan was created using an 8 mm isotropic margin, except 5 mm posteriorly, to
      account for lack of intrafraction tracking. RESULTS: Both RapidArc and Multiplan
      can produce clinically acceptable boost plans to a dose of 47.5 Gy in 5
      fractions. The mean rectal doses were lower for RapidArc plans (D50 13.2 Gy vs
      15.5 Gy) but the number of missed constraints was the same for both planning
      methods (11/75). When the margin was increased to 8 mm/5 mm for the RapidArc
      plans to account for intrafraction motion, 37/75 constraints were missed.
      CONCLUSIONS: RapidArc and Multiplan can produce clinically acceptable
      simultaneous integrated boost plans, but the mean rectal D50 and D20 with
      RapidArc are lower. If the margins are increased to account for intrafraction
      motion, the RapidArc plans exceed at least one dose constraint in 13/15 cases.
      Delivering a simultaneous boost with hypofractionation appears feasible, but
      requires small margins needing intrafraction motion tracking.

PMID- 24088322
TI  - Evolution of complete proteomes: guanine-cytosine pressure, phylogeny and
      environmental influences blend the proteomic architecture.
AB  - BACKGROUND: Guanine-cytosine (GC) composition is an important feature of genomes.
      Likewise, amino acid composition is a distinct, but less valued, feature of
      proteomes. A major concern is that it is not clear what valuable information can
      be acquired from amino acid composition data. To address this concern, in-depth
      analyses of the amino acid composition of the complete proteomes from 63 archaea,
      270 bacteria, and 128 eukaryotes were performed. RESULTS: Principal component
      analysis of the amino acid matrices showed that the main contributors to
      proteomic architecture were genomic GC variation, phylogeny, and environmental
      influences. GC pressure drove positive selection on Ala, Arg, Gly, Pro, Trp, and
      Val, and adverse selection on Asn, Lys, Ile, Phe, and Tyr. The physico-chemical
      framework of the complete proteomes withstood GC pressure by frequency
      complementation of GC-dependent amino acid pairs with similar physico-chemical
      properties. Gln, His, Ser, and Val were responsible for phylogeny and their
      constituted components could differentiate archaea, bacteria, and eukaryotes.
      Environmental niche was also a significant factor in determining proteomic
      architecture, especially for archaea for which the main amino acids were Cys,
      Leu, and Thr. In archaea, hyperthermophiles, acidophiles, mesophiles,
      psychrophiles, and halophiles gathered successively along the environment-based
      principal component. Concordance between proteomic architecture and the genetic
      code was also related closely to genomic GC content, phylogeny, and lifestyles.
      CONCLUSIONS: Large-scale analyses of the complete proteomes of a wide range of
      organisms suggested that amino acid composition retained the trace of GC
      variation, phylogeny, and environmental influences during evolution. The findings
      from this study will help in the development of a global understanding of
      proteome evolution, and even biological evolution.

PMID- 24088323
TI  - The large soybean (Glycine max) WRKY TF family expanded by segmental duplication
      events and subsequent divergent selection among subgroups.
AB  - BACKGROUND: WRKY genes encode one of the most abundant groups of transcription
      factors in higher plants, and its members regulate important biological process
      such as growth, development, and responses to biotic and abiotic stresses.
      Although the soybean genome sequence has been published, functional studies on
      soybean genes still lag behind those of other species. RESULTS: We identified a
      total of 133 WRKY members in the soybean genome. According to structural features
      of their encoded proteins and to the phylogenetic tree, the soybean WRKY family
      could be classified into three groups (groups I, II, and III). A majority of WRKY
      genes (76.7%; 102 of 133) were segmentally duplicated and 13.5% (18 of 133) of
      the genes were tandemly duplicated. This pattern was not apparent in Arabidopsis
      or rice. The transcriptome atlas revealed notable differential expression in
      either transcript abundance or in expression patterns under normal growth
      conditions, which indicated wide functional divergence in this family.
      Furthermore, some critical amino acids were detected using DIVERGE v2.0 in
      specific comparisons, suggesting that these sites have contributed to functional
      divergence among groups or subgroups. In addition, site model and branch-site
      model analyses of positive Darwinian selection (PDS) showed that different
      selection regimes could have affected the evolution of these groups. Sites with
      high probabilities of having been under PDS were found in groups I, II c, II e,
      and III. Together, these results contribute to a detailed understanding of the
      molecular evolution of the WRKY gene family in soybean. CONCLUSIONS: In this
      work, all the WRKY genes, which were generated mainly through segmental
      duplication, were identified in the soybean genome. Moreover, differential
      expression and functional divergence of the duplicated WRKY genes were two major
      features of this family throughout their evolutionary history. Positive selection
      analysis revealed that the different groups have different evolutionary rates.
      Together, these results contribute to a detailed understanding of the molecular
      evolution of the WRKY gene family in soybean.

PMID- 24088324
TI  - Continuous regional arterial infusion for acute pancreatitis: a propensity score
      analysis using a nationwide administrative database.
AB  - INTRODUCTION: Although continuous regional arterial infusion (CRAI) of a protease
      inhibitor and an antibiotic may be effective in patients with severe acute
      pancreatitis, CRAI has not yet been validated in large patient populations. We
      therefore evaluated the effectiveness of CRAI based on data from a national
      administrative database covering 1,032 Japanese hospitals. METHODS: In-hospital
      mortality, length of stay and costs were compared in the CRAI and non-CRAI
      groups, using propensity score analysis to adjust for treatment selection bias.
      RESULTS: A total of 17,415 eligible patients with acute pancreatitis were
      identified between 1 July and 30 September 2011, including 287 (1.6%) patients
      who underwent CRAI. One-to-one propensity-score matching generated 207 pairs with
      well-balanced baseline characteristics. In-hospital mortality rates were similar
      in the CRAI and non-CRAI groups (7.7% vs. 8.7%; odds ratio, 0.88; 95% confidence
      interval, 0.44-1.78, P = 0.720). CRAI was associated with significantly longer
      median hospital stay (29 vs. 18 days, P < 0.001), significantly higher median
      total cost (21,800 vs. 12,600 United States dollars, P < 0.001), and a higher
      rate of interventions for infectious complications, such as endoscopic/surgical
      necrosectomy or percutaneous drainage (2.9% vs. 0.5%, P = 0.061). CONCLUSIONS:
      CRAI was not effective in reducing in-hospital mortality rate in patients with
      acute pancreatitis, but was associated with longer hospital stay and higher
      costs. Randomized controlled trials in large numbers of patients are required to
      further evaluate CRAI for this indication.

PMID- 24088325
TI  - Lymphatic absorption, metabolism, and excretion of a therapeutic peptide in dogs
      and rats.
AB  - The objective of the current study was to evaluate the mechanism of absorption
      and metabolism of a PEGylated peptide, MRL-1 (46 kDa), after s.c. dosing in dogs
      and rats. Thoracic lymph duct-cannulated (LDC) dog and rat models were developed
      that allowed continuous collection of lymph for up to 8 days. When [(3)H]MRL-1
      was administered s.c. to LDC dogs, ~73% of the administered radioactivity was
      recovered in pooled lymph over a period of 120 hours, suggesting that lymphatic
      uptake is the major pathway of s.c. absorption for this peptide. In agreement
      with these data, the systemic exposure of radioactivity related to [(3)H]MRL-1 in
      LDC dogs was decreased proportionately when compared with that in noncannulated
      control dogs. After i.v. dosing with [(3)H]MRL-1 in LDC dogs, 20% of the
      administered radioactivity was recovered in pooled lymph over 168 hours,
      suggesting some level of recirculation of radioactivity related to [(3)H]MRL-1
      from the plasma compartment into the lymphatic system. Experiments conducted in
      the LDC rat model also resulted in similar conclusions. Analysis of injection
      site s.c. tissue showed significant metabolism of [(3)H]MRL-1, which provides an
      explanation for the <100% bioavailability of therapeutic proteins and peptides
      after s.c. dosing. After s.c. dosing, the major circulating components in plasma
      were the parent peptide and the PEG-linker [(3)H]MRL-2. The metabolism profiles
      in lymph were similar to those in plasma, suggesting that the loss of peptide was
      minimal during lymphatic transport. After i.v. dosing in rats, [(3)H]MRL-1 was
      metabolized and excreted primarily in the urine as metabolites. 

PMID- 24088326
TI  - Modulation of the UGT2B7 enzyme activity by C-terminally truncated proteins
      derived from alternative splicing.
AB  - The enzyme UGT2B7 is one of the most active UDP-glucuronosyltransferases (UGTs)
      involved in drug metabolism and in maintaining homeostasis of endogenous
      compounds. We recently reported the existence of 22 UGT2B7 mRNAs, two with a
      classic 5' region but alternative 3' ends namely UGT2B7_v5 (containing a novel
      terminal exon 6b) and _v7 (exon 5 excluded) that encode enzymatically inactive
      isoforms 2 and 4 (i2 and i4), respectively. The v1 mRNA encoding the UGT2B7
      enzyme (renamed isoform 1 or i1) is coexpressed with the splice variants v5 and
      v7 in human liver, kidney, and small intestine and the hepatic cell lines HepG2
      and C3A. The presence of alternate v5 and v7 transcripts in isolated polysomes
      from these hepatic cells further supports endogenous protein translation.
      Cellular fractionation of clonal HEK293 cell lines overexpressing UGT2B7 isoforms
      demonstrates that i1, i2, and i4 proteins colocalize in the microsomal/Golgi
      fraction, whereas i2 and i4 can also be found in the cytosol; a finding sustained
      by immunofluorescence experiments using tagged proteins. By modifying splice
      variant abundance in overexpression in HEK293 and HepG2 cells as well as RNA
      interference experiments in HepG2 and C3A cells, we observe drug glucuronidation
      phenotypes compatible with variant-mediated repression of UGT2B7 activity without
      consequent alteration of the apparent enzyme affinity (K(m)). Finally,
      coimmunoprecipitation experiments support a direct protein-protein interaction of
      i2 and i4 proteins with the functional UGT2B7 enzyme as a potential causative
      mechanism. These findings point toward a novel autoregulatory mechanism of the
      UGT2B7 glucuronidation pathway by naturally occurring alternative i2 and i4
      proteins.

PMID- 24088327
TI  - Associations between sports participation, adiposity and obesity-related health
      behaviors in Australian adolescents.
AB  - BACKGROUND: The purpose of this study was to examine the relationship between
      organized sports participation, weight status, physical activity, screen time,
      and important food habits in a large nationally representative sample of
      Australian adolescents. METHODS: Nationally representative cross-sectional study
      of 12,188 adolescents from 238 secondary schools aged between 12 and 17 years
      (14.47 +/- 1.25 y, 53% male, 23% overweight/obese). Participation in organized
      sports, compliance with national physical activity, screen time, and fruit and
      vegetable consumption guidelines, and consumption of sugar-sweetened beverages
      and high-fat foods were self-reported. Weight status and adiposity (BMI, waist
      circumference) were measured. RESULTS: Organized sports participation was higher
      among males and those residing in rural/remote areas. Underweight adolescents
      reported the lowest levels of participation. Higher levels of participation were
      associated with an increased likelihood of complying with national physical
      activity (OR = 2.07 [1.67-2.58]), screen time (OR = 1.48 [1.19-1.84]), and fruit
      and vegetable consumption guidelines (OR = 1.32 [1.05-1.67]). There was no
      association between organized sport participation and weight status, adiposity,
      consumption of sugar-sweetened beverages or high-fat foods. CONCLUSIONS:
      Participation in organized sports was associated with a greater likelihood to
      engage in a cluster of health behaviors, including meeting physical activity
      guidelines, electronic screen time recommendations, and fruit and vegetable
      consumption guidelines. However, participation in organized sports was not
      associated with unhealthy dietary behaviors including the consumption of sugar
      sweetened beverages and high-fat foods. There is no association between
      participation in organized sports and likelihood to be overweight or obese. The
      role of sports in promoting healthy weight and energy balance is unclear.

PMID- 24088328
TI  - Devastating metabolic consequences of a life of plenty: focus on the dyslipidemia
      of overnutrition.
AB  - Although undernutrition and starvation continue to affect a substantial portion
      of the world's population, billions of people in both developed and developing
      countries are affected by the opposite problem: consumption of calories that
      exceed their daily energy expenditure, a condition of overnutrition. The body's
      response to a positive net energy balance is to store energy, predominantly as
      triglyceride molecules, in the subcutaneous and visceral fat compartments that
      expand and ultimately manifest in obesity. The body's fat depot, however, does
      not have an infinite capacity to store and expand, and at set points, which
      differ from individual to individual and are also influenced by ethnicity, energy
      substrates 'spill over', resulting in 'ectopic' fat storage in tissues and organs
      that are not typically major fat storage depots in lean individuals. A complex
      web of nutrient overload, chronic inflammation, hormonal action, mitochondrial
      dysfunction and insulin resistance, to mention some of the factors involved,
      results in devastating metabolic abnormalities that have far reaching
      implications for health and disease, leading ultimately to some of the most
      common chronic diseases of our time; i.e., diabetes mellitus, cancer, chronic
      liver disease and atherosclerosis. Given the complexity and wide-ranging
      manifestations of overnutrition (also referred to here as insulin resistant
      states), we will highlight a specific aspect of the condition, that of
      dyslipidemia. This review will draw mainly on knowledge acquired from whole body,
      integrative physiology research in animals and humans affected by overnutrition,
      and will demonstrate how these types of studies can shed light on our
      understanding of the pathophysiology of the typical dyslipidemia of obesity,
      insulin resistance and type 2 diabetes. 

PMID- 24088329
TI  - Scientific overview: CSCI - CITAC Annual General Meeting and Young Investigator's
      Forum 2012.
AB  - In 2012, the Annual General Meeting of the Clinical Investigator Trainee
      Association of Canada - Association des cliniciens-chercheurs en formation du
      Canada (CITAC - ACCFC) and the Canadian Society of Clinician Investigators (CSCI)
      was held 19-21 September in Ottawa. Several globally-renowned scientists,
      including 2012 Friesen International Prize recipient, Dr. Marc Tessier-Lavigne,
      the CSCI/Royal College Henry Friesen Award recipient, Dr. Morley Hollenberg, and
      the recipient of the Joe Doupe Young Investigator Award, Dr. Phillip Awadalla,
      presented on a range of topics on research in basic and translational science in
      medicine. This year's CITAC Symposium featured presentations by Dr. Alain
      Beaudet, Dr. Michael Strong and Dr. Vivek Goel on the Role of Physician
      Scientists in Public Health and Policy, which was followed by a lively discussion
      on the role of basic science and clinical research in patient-oriented policy
      development. This scientific overview highlights the research presented by
      trainees at both the oral plenary and poster presentation sessions. As at
      previous meetings, research questions investigated by this year's trainees span
      multiple medical disciplines; from basic science to clinical research to medical
      education. Below is a summary of the presentations showcased at the Young
      Investigator's Forum. 

PMID- 24088330
TI  - Here to stay: clinician investigator training in a changing environment.
AB  - Clinician investigators (CI) are a growing sector within the research community.
      Given the emphasis on patient-oriented research, the need for more physicians
      with the aptitude to conduct translational research has never been greater.
      Despite this, there is limited literature on the current Canadian CI training
      programs. The Clinician Investigator Trainee Association of Canada (CITAC) has a
      significant interest in ensuring the training of clinician instigators, at both
      the undergraduate and residency levels, remains adept at meeting the challenges
      of today's health care system. In the August issue of Clinical Investigative
      Medicine, Appleton et al. published the first document reporting on the data
      collected by CITAC on the basic demographics of Canadian CI trainees [3]. The
      authors captured census data from each CI training program. This collaborative
      and national effort is a first and crucial step in understanding the strengths
      and potential pitfalls of Canadian CI training programs. The data presented will
      be used as a reference resource to improve training programs and facilitate
      future research. 

PMID- 24088331
TI  - Influence of cardiac dysfunction and systemic inflammation on pulmonary function
      and airway responsiveness in obese subjects.
AB  - PURPOSE: Obesity is associated with left ventricular diastolic dysfunction and
      altered heart rate variability, as well as pulmonary dysfunction. The
      relationship between asthma and cardiac dysfunction in severely obese subjects is
      unknown, although it has been hypothesized that cardiac dysfunction may
      contribute to increase airway hyper-responsiveness (AHR). This study aimed to
      determine if AHR is associated with left ventricular diastolic dysfunction and
      heart rate variability in severely obese subjects. METHODS: Sixty-one subjects
      with severe obesity (BMI >=35 kg/m2 with comorbidities) completed this study. All
      subjects completed respiratory questionnaires, spirometry, lung volume
      measurements, methacholine inhalation test, 24hour Holter monitoring and a
      complete echocardiography evaluation. Blood samples were obtained for measurement
      of metabolic markers. Subjects with AHR, defined by a provocative concentration
      of methacholine inducing a 20% fall in FEV1 (PC20) < 8 mg/ml, were compared with
      those with no AHR (PC20 >=8 mg/ml). RESULTS: According to these criteria, 32
      subjects had AHR and 29 had no AHR(mean PC201.70 mg/ml and 15.3 mg/ml
      respectively, p < 0.001). The groups were similar for anthropometric data and
      comorbidities. Fasting glucose, Hb1Ac, total cholesterol, LDL, triglycerides, Apo
      B, C-reactive protein (CRP) and pro-BNP levels were also comparable between
      groups (p > 0.05). CRP level correlated with PC20 (AHR, r=0.38, p=0.03). Indices
      of heart rate variability and overall cardiac function were similar in subjects
      with or without AHR but grade 2 left ventricular diastolic dysfunction was more
      prevalent in subjects with AHR (p=0.037). CONCLUSIONS: Altered cardiac function,
      dysglycemia and dyslipidemia do not seem to be significantly associated with AHR
      in severely obese subjects in contrast to systemic inflammation.

PMID- 24088332
TI  - Serum fetuin-A levels following recombinant human thyroid-stimulating hormone
      stimulation.
AB  - PURPOSE: Fetuin-A is a hepatokine that is linked to lipid metabolism, obesity,
      insulin resistance, type 2 diabetes and cardiovascular disease. Elevated thyroid
      stimulating hormone (TSH) levels are associated with metabolic and cardiovascular
      disturbances. Our aim was to determine if TSH can regulate fetuin-A levels.
      METHODS: Fetuin-A serum levels were examined in 26 subjects (19 women; previous
      thyroidectomy and radioactive iodine ablation) undergoing recombinant human TSH
      (rhTSH) stimulation to screen for thyroid cancer recurrence. Their age was 49+/
      10 years, and body mass index (BMI) was 28+/-6 (both expressed as mean+/-SD). The
      patients received two doses of rhTSH (0.9 mg), administered 24 hours apart on
      days 1 and 2, without discontinuation of ongoing L-thyroxine therapy. Morning
      blood samples were obtained on days 1 (prior to the first dose of rhTSH), 3 and
      5. RESULTS: The baseline value of fetuin-A (mean+/-SD) for all participants was
      527+/-186 mg/L. Values of fetuin-A did not change in response to rhTSH
      administration. The lack of response was not dependent on gender, age, baseline
      free thyroxine level or BMI. CONCLUSION: Fetuin-A has been implicated in
      metabolic and inflammatory conditions, but there have been no reports on whether
      fetuin-A is influenced by TSH. Within the context of rhTSH administration for
      surveillance of thyroid cancer recurrence, there was no effect on serum levels of
      fetuin-A.

PMID- 24088333
TI  - Towards a science of rabies elimination.
AB  - Wenwu Yin and co-workers conducted a systematic review on challenges and needs to
      eliminate rabies in China (Yin et al., 2013 in this journal). Their analysis
      shows that there is considerable overrepresentation of laboratory and basic
      epidemiology research. On the other hand, information on effective control
      activities and policies are nearly absent. Currently we know enough to control
      and eliminate dog rabies effectively. Continuing basic research while not
      engaging in the control of rabies appears almost cynical. Why is it not
      attractive to do research on effective control and elimination? Let us move now
      from the biological understanding to the science of rabies elimination. 

PMID- 24088334
TI  - Matrix theory for baryons: an overview of holographic QCD for nuclear physics.
AB  - We provide, for non-experts, a brief overview of holographic QCD (quantum
      chromodynamics) and a review of the recent proposal (Hashimoto et al 2010
      (arXiv:1003.4988[hep-th])) of a matrix-like description of multi-baryon systems
      in holographic QCD. Based on the matrix model, we derive the baryon interaction
      at short distances in multi-flavor holographic QCD. We show that there is a very
      universal repulsive core of inter-baryon forces for a generic number of flavors.
      This is consistent with a recent lattice QCD analysis for Nf = 2, 3 where the
      repulsive core looks universal. We also provide a comparison of our results with
      the lattice QCD and the operator product expansion analysis. 

PMID- 24088337
TI  - Transposable element evolution in Heliconius suggests genome diversity within
      Lepidoptera.
AB  - BACKGROUND: Transposable elements (TEs) have the potential to impact genome
      structure, function and evolution in profound ways. In order to understand the
      contribution of transposable elements (TEs) to Heliconius melpomene, we queried
      the H. melpomene draft sequence to identify repetitive sequences. RESULTS: We
      determined that TEs comprise ~25% of the genome. The predominant class of TEs
      (~12% of the genome) was the non-long terminal repeat (non-LTR) retrotransposons,
      including a novel SINE family. However, this was only slightly higher than
      content derived from DNA transposons, which are diverse, with several families
      having mobilized in the recent past. Compared to the only other well-studied
      lepidopteran genome, Bombyx mori, H. melpomene exhibits a higher DNA transposon
      content and a distinct repertoire of retrotransposons. We also found that H.
      melpomene exhibits a high rate of TE turnover with few older elements
      accumulating in the genome. CONCLUSIONS: Our analysis represents the first
      complete, de novo characterization of TE content in a butterfly genome and
      suggests that, while TEs are able to invade and multiply, TEs have an overall
      deleterious effect and/or that maintaining a small genome is advantageous. Our
      results also hint that analysis of additional lepidopteran genomes will reveal
      substantial TE diversity within the group.

PMID- 24088338
TI  - An evaluation of prescribing practices for community-acquired pneumonia (CAP) in
      Mongolia.
AB  - BACKGROUND: Community-acquired pneumonia (CAP) is a significant cause of
      morbidity and mortality in all age groups worldwide. It may be classified as
      mild/moderate or severe, the latter usually requiring hospitalisation. Although,
      there are many studies reported in relation to CAP, there is relatively little
      known about the treatment of CAP and its antibiotic use in Mongolia. The study
      aim was to evaluate prescribing practices for the treatment of mild/moderate CAP
      in Mongolia with respect to national prescribing guidelines. METHODS: Written
      prescriptions with a written diagnosis of CAP included were collected
      prospectively and sequentially for ten weeks from a purposefully selected sample
      of community pharmacies in rural and urban areas of Mongolia. The data collected
      included the patient's age, gender, medication details, frequency and number of
      doses prescribed. Evaluation was with respect to the Mongolian Standard Treatment
      Guidelines (2005, 2008). Statistical differences between groups were tested using
      the Chi-squared and Fisher's exact tests. RESULTS: Prescriptions were collected
      from 22 pharmacies and represented the prescribing practices of 118 doctors. The
      study enrolled 394 (193 adults and 201 children) patients, with a median age for
      children of 2.0 years (range: 0.03-12) and adults of 33.0 years (range: 13
      92).The most commonly prescribed drugs were aminopenicillins, vitamins, and
      mucolytics, with the median number of drugs being three per prescription.
      Inappropriate drug selection was similar for adults (57.7%) and children (56.6%),
      and the major reason for an overall frequency of inappropriate prescribing for
      adults was 89.0% and for children 78.0%. Doctors in urban areas prescribed more
      inappropriate drugs than those in rural areas for both children and adults, p =
      .0014. The proportion of prescribed injections was 28.4% for adults and 9.0% for
      children, and for adults was significantly higher in urban areas. The prescribing
      standard for non-hospitalized patients in Mongolia states that injections should
      not be prescribed. CONCLUSIONS: The high level of inappropriate prescribing for
      mild/moderate CAP highlights the need to develop comprehensive and reliable
      procedures nationwide to improve prescribing practices in Mongolia.

PMID- 24088339
TI  - Natural hybrids between Tragopogon mirus and T. miscellus (Asteraceae): a new
      perspective on karyotypic changes following hybridization at the polyploid level.
AB  - PREMISE OF THE STUDY: Natural hybrids have formed in Pullman, Washington, United
      States between the recently formed allotetraploids Tragopogon miscellus and T.
      mirus. In addition to forming spontaneously, these hybrids are semifertile,
      propagating via achenes. Previous work indicated that the tetraploid hybrids have
      genetic contributions from three progenitor diploids: T. dubius, T. pratensis,
      and T. porrifolius. Because the hybrids contain genomes from three species, they
      should be karyotypically variable and have very low fertility. To better
      understand how these hybrids are semifertile, we applied fluorescent probes to
      determine chromosome composition. * METHODS: We sequentially conducted
      fluorescence and genomic in situ hybridization to generate karyotypes for five
      hybrid individuals grown from field-collected achenes. * KEY RESULTS: All plants
      had the expected somatic chromosome number (2n = 24), but none showed an additive
      F1 chromosome complement, i.e., two sets of chromosomes from T. dubius and one
      set of chromosomes each from T. porrifolius and T. pratensis. No individuals
      shared an identical karyotype, but chromosomal variation followed a compensatory
      pattern of substitutions, with all groups of putatively homeologous chromosomes
      consistently totaling four. * CONCLUSIONS: The hybrids appear to be shifting away
      from a parentally additive F1 karyotype to chromosomal compositions that are
      mostly, or entirely, disomic. We hypothesize that this process may eventually
      lead to the elimination of chromosomes from a population and produce a stabilized
      karyotype distinct from both allotetraploid parents. This work has implications
      for other hybrids formed between polyploids, in that they may be hard to detect
      using sequence data alone due to multilateral patterns of chromosome elimination.

PMID- 24088340
TI  - Hybridization leads to interspecific gene flow in Sarracenia (Sarraceniaceae).
AB  - PREMISE OF THE STUDY: The role of hybridization in plant evolution remains a
      source of intense debate. Potential consequences range from genetic dead-ends to
      species fusion or hybrid speciation. While much has been learned from model
      systems such as Populus, Iris, and Helianthus, many questions remain. Consisting
      of 11 species that are all capable of hybridizing, Sarracenia presents an
      excellent system in which to study hybridization. * METHODS: Using
      microsatellites, we examined a single field site consisting of three species: S.
      leucophylla, S. alata, and S. rubra subsp. wherryi. We determined the level of
      genetic admixture and compared it with allopatric sites of the same taxa. * KEY
      RESULTS: In contrast to the well-defined clusters formed when we examined the
      allopatric sites, the sympatric field site exhibited a wide range of admixture.
      Additionally, when the relative genetic makeup of "pure" species at the site was
      compared with the makeup of hybrids, we found that Sarracenia alata contributed
      disproportionately to the hybrid genomes. * CONCLUSIONS: Our study provides
      further evidence that hybridization is contributing to interspecific gene flow in
      the genus and that all species do not contribute equally to hybridization.
      Implications for conservation are discussed.

PMID- 24088341
TI  - Genetic diversity in three endangered pitcher plant species (Sarracenia;
      Sarraceniaceae) is lower than widespread congeners.
AB  - PREMISE OF THE STUDY: Narrow-ranging, rare species often exhibit levels of
      genetic diversity lower than more common or widespread congeners. These taxa are
      at increased risk of extinction due to threats associated with natural as well as
      anthropogenic events. We assessed genetic variation in three federally endangered
      Sarracenia species. We discuss maintenance of genetic diversity and evolutionary
      implications of rarity. * METHODS: We analyzed three noncoding chloroplast
      regions and nine microsatellite loci in populations spanning the geographic
      ranges of S. oreophila, S. alabamensis, and S. jonesii. The same microsatellite
      loci were used to examine a single field site of three more widespread species
      (S. alata, S. leucophylla, and S. rubra subsp. wherryi). * KEY RESULTS: All three
      endangered species have experienced reductions in population size and numbers.
      All show considerably less variation than more widespread members of the genus.
      Sarracenia alabamensis maintains the greatest microsatellite variation but has
      the fewest remaining populations and may be under the greatest threat. More
      widespread S. oreophila maintains surprising chloroplast diversity, yet exhibits
      little microsatellite diversity. Sarracenia jonesii lacks chloroplast diversity,
      yet maintains greater microsatellite diversity than S. oreophila. * CONCLUSIONS:
      The three endangered species differ in levels and structure of diversity, yet not
      in predictable ways, emphasizing that unique demographic and ecological
      histories, rather than current distribution and population size, best explain
      present patterns of genetic variation. Maintenance of remaining genetic variation
      is important, but preventing further habitat loss and degradation is critical.

PMID- 24088342
TI  - Balance ability and postural stability among patients with painful shoulder
      disorders and healthy controls.
AB  - BACKGROUND: In therapeutic settings, patients with shoulder pain often exhibit
      deficient coordinative abilities in their trunk and lower extremities. The aim of
      the study was to investigate 1) if there is a connection between shoulder pain
      and deficits in balance ability and postural stability, 2) if pain intensity is
      related to balance ability and postural stability, and 3) if there is a
      connection between body mass index (BMI) and balance ability and postural
      stability. METHODS: In this case-control study, patients (n = 40) with
      pathological shoulder pain (> 4 months) were matched with a healthy controls (n =
      40) and were compared with regard to their balance ability and postural
      stability. Outcome parameters were postural stability, balance ability and
      symmetry index which were measured using the S3-Check system. In addition, the
      influence of shoulder pain intensity and BMI on the outcome parameters was
      analysed. RESULTS: Patients with shoulder pain showed significantly worse results
      in measurements of postural stability right/left (p < 0.01) and front/back (p <
      0.01) as well as balance ability right/left (p = 0.01) and front/back (p < 0.01)
      compared to healthy controls. There were no significant group differences with
      regard to symmetry index. However, there was a significant (p < 0.01) symmetry
      shift towards the affected side within the shoulder pain group. There was no
      correlation between pain intensity and measurements of balance ability or
      postural stability. Likewise, no correlation between BMI and deficiencies in
      balance ability and postural stability was established. CONCLUSIONS: Patients
      with pathological shoulder pain (> 4 months) have deficiencies in balance ability
      and postural stability; however the underlying mechanisms for this remain
      unclear. Neither pain intensity nor BMI influenced the outcome parameters.
      Patients with shoulder pain shift their weight to the affected side. Further
      research is needed to determine if balance training can improve rehabilitation
      results in patients with shoulder pathologies.

PMID- 24088343
TI  - Pulmonary hypertension secondary to hyperviscosity in a patient with rheumatoid
      arthritis and acquired von Willebrand disease: a case report.
AB  - INTRODUCTION: Acquired von Willebrand disease is initiated by autoantibodies and
      hyperviscosity syndrome caused by a massive polyclonal hypergammaglobulinemia.
      Acquired von Willebrand disease associated with autoimmune disease in addition to
      pulmonary hypertension during emergency room presentation is a rare condition. To
      the best of our knowledge, this is the second case reported in the literature
      treated with success; the first one was reported in 1987. CASE PRESENTATION: A 28
      year-old mestizo man with a 3-year history of inflammatory arthritis was admitted
      to our hospital. An overlap of rheumatoid arthritis with systemic lupus
      erythematosus was suspected; therefore methotrexate was initiated, and later
      changed to leflunomide because of liver toxicity. Prothrombin time, international
      normalized ratio and activated partial thromboplastin times were normal (11/10.4
      seconds; 1.2; 31.1/26.9 seconds, respectively), von Willebrand factor activity
      was observed with low ristocetin cofactor at 33.6UI/dL, high von Willebrand
      factor antigen >200UI/dL, and a low von Willebrand factor: ristocetin cofactor to
      von Willebrand factor antigen ratio. He was admitted to the emergency room with a
      24-hour evolution of progressive dyspnea, cough, thoracic pain, and palpitations,
      104 beats/min, 60/40 mmHg, temperature of 38 degrees C, pulse oximetric
      saturation 88% and 30 breaths/minute. Cold, pale and mottled skin was also
      observed. He was then transferred to the intensive care unit. The placement of a
      pulmonary artery catheter was made. The initial patterns showed a precapillary
      pulmonary hypertension; acute pulmonary embolism was the first choice for
      diagnosis. Pulmonary angiography was conducted, and when no clot was discovered,
      pulmonary artery hypertension associated with connective tissue disease was
      considered. Serum protein electrophoresis confirmed the presence of a massive
      polyclonal hypergammaglobulinemia, and no paraproteinemia or monoclonal cell
      population was found from the electrophoretic pattern of the patient's plasma.
      Hypergammaglobulinemia was the cause of hyperviscosity syndrome associated with
      autoantibodies. Three sessions of plasma exchange therapy were made, and clinical
      improvement was observed. He was then discharged from the intensive care unit and
      hospital, respectively. He is now attended by an external consult and has no
      respiratory symptomatology. CONCLUSIONS: Hyperviscosity syndrome with pulmonary
      arterial hypertension presentation in a patient with acquired von Willebrand
      disease in an autoimmune context is a rare condition that can be treated
      successfully with plasmapheresis and critical care support.

PMID- 24088345
TI  - A strain-specific segment of the RNA-dependent RNA polymerase of grapevine
      fanleaf virus determines symptoms in Nicotiana species.
AB  - Factors involved in symptom expression of viruses from the genus Nepovirus in the
      family Secoviridae such as grapevine fanleaf virus (GFLV) are poorly
      characterized. To identify symptom determinants encoded by GFLV, infectious cDNA
      clones of RNA1 and RNA2 of strain GHu were developed and used alongside existing
      infectious cDNA clones of strain F13 in a reverse genetics approach. In vitro
      transcripts of homologous combinations of RNA1 and RNA2 induced systemic
      infection in Nicotiana benthamiana and Nicotiana clevelandii with identical
      phenotypes to WT virus strains, i.e. vein clearing and chlorotic spots on N.
      benthamiana and N. clevelandii for GHu, respectively, and lack of symptoms on
      both hosts for F13. The use of assorted transcripts mapped symptom determinants
      on RNA1 of GFLV strain GHu, in particular within the distal 408 nt of the RNA
      dependent RNA polymerase (1E(Pol)), as shown by RNA1 transcripts for which coding
      regions or fragments derived thereof were swapped. Semi-quantitative analyses
      indicated no significant differences in virus titre between symptomatic and
      asymptomatic plants infected with various recombinants. Also, unlike the
      nepovirus tomato ringspot virus, no apparent proteolytic cleavage of GFLV protein
      1E(Pol) was detected upon virus infection or transient expression in N.
      benthamiana. In addition, GFLV protein 1E(Pol) failed to suppress silencing of
      EGFP in transgenic N. benthamiana expressing EGFP or to enhance GFP expression in
      patch assays in WT N. benthamiana. Together, our results suggest the existence of
      strain-specific functional domains, including a symptom determinant module, on
      the RNA-dependent RNA polymerase of GFLV. 

PMID- 24088346
TI  - A reappraisal of success factors for Olympic cross-country skiing.
AB  - Cross-country (XC) skiing has been an Olympic event since the first Winter Games
      in Chamonix, France, in 1924. Due to more effective training and tremendous
      improvements in equipment and track preparation, the speed of Olympic XC-ski
      races has increased more than that of any other Olympic endurance sport.
      Moreover, pursuit, mass-start, and sprint races have been introduced. Indeed, 10
      of the 12 current Olympic competitions in XC skiing involve mass starts, in which
      tactics play a major role and the outcome is often decided in the final sprint.
      Accordingly, reappraisal of the success factors for performance in this context
      is required. The very high aerobic capacity (VO2max) of many of today's world
      class skiers is similar that of their predecessors. At the same time, the new
      events provide more opportunities to profit from anaerobic capacity, upper-body
      power, high-speed techniques, and "tactical flexibility." The wide range of
      speeds and slopes involved in XC skiing requires skiers to continuously alternate
      between and adapt different subtechniques during a race. This technical
      complexity places a premium on efficiency. The relative amounts of endurance
      training performed at different levels of intensity have remained essentially
      constant during the past 4 decades. However, in preparation for the Sochi
      Olympics in 2014, XC skiers are performing more endurance training on roller skis
      on competition-specific terrain, placing greater focus on upper-body power and
      more systematically performing strength training and skiing at high speeds than
      previously. 

PMID- 24088344
TI  - Identification of the domains of cauliflower mosaic virus protein P6 responsible
      for suppression of RNA silencing and salicylic acid signalling.
AB  - Cauliflower mosaic virus (CaMV) encodes a 520 aa polypeptide, P6, which
      participates in several essential activities in the virus life cycle including
      suppressing RNA silencing and salicylic acid-responsive defence signalling. We
      infected Arabidopsis with CaMV mutants containing short in-frame deletions within
      the P6 ORF. A deletion in the distal end of domain D-I (the N-terminal 112 aa) of
      P6 did not affect virus replication but compromised symptom development and
      curtailed the ability to restore GFP fluorescence in a GFP-silenced transgenic
      Arabidopsis line. A deletion in the minimum transactivator domain was defective
      in virus replication but retained the capacity to suppress RNA silencing locally.
      Symptom expression in CaMV-infected plants is apparently linked to the ability to
      suppress RNA silencing. When transiently co-expressed with tomato bushy stunt
      virus P19, an elicitor of programmed cell death in Nicotiana tabacum, WT P6
      suppressed the hypersensitive response, but three mutants, two with deletions
      within the distal end of domain D-I and one involving the N-terminal nuclear
      export signal (NES), were unable to do so. Deleting the N-terminal 20 aa also
      abolished the suppression of pathogen-associated molecular pattern-dependent PR1a
      expression following agroinfiltration. However, the two other deletions in domain
      D-I retained this activity, evidence that the mechanisms underlying these
      functions are not identical. The D-I domain of P6 when expressed alone failed to
      suppress either cell death or PR1a expression and is therefore necessary but not
      sufficient for all three defence suppression activities. Consequently, concerns
      about the biosafety of genetically modified crops carrying truncated ORFVI
      sequences appear unfounded. 

PMID- 24088347
TI  - [Neuropharmacological study of ATP receptors and their role in neuropathic pain].
AB  - A growing body of evidence indicates that extracellular nucleotides released or
      leaked from non-excitable cells as well as neurons play important roles in the
      regulation of neuronal and glial functions in the whole body through ATP
      receptors. ATP receptors (ionotropic P2X and metabotropic P2Y receptors) are the
      most abundant receptor families in living organisms. In the central nervous
      system, these receptors participate in synaptic transmission and in intercellular
      communications between neurons and glia. Glia cells are classified into
      astrocytes, oligodendrocytes and microglia. There are many reports on the role of
      ATP receptors (P2X4, P2X7, P2Y6 and P2Y12 receptors) expressed in spinal
      microglia. We have reported that several molecules presumably activate microglia
      in neuropathic pain after peripheral nerve injury. P2X4 receptors expressed in
      microglia in particular play a critical role in neuropathic pain signaling. The
      expression and activity of P2X4 receptors are up-regulated and enhanced
      predominantly in activated microglia in the spinal cord where damaged sensory
      fibers project. These findings provide novel targets for developing new medicines
      to treat neuropathic pain.

PMID- 24088348
TI  - [Development of selective detection method for 5-formyl-2'-deoxyuridine in DNA
      using a fluorogenic reagent].
AB  - It is important that various lesions in DNA were detected selectively and
      conveniently to know mechanisms of carcinogenicity and/or aging of cells.
      However, most detection methods of DNA lesion are complicated and take a long
      time for enzymatic hydrolysis and analysis by HPLC and/or mass spectrometry. This
      review shows the new concept for detection of DNA lesion by "fluorogenic
      reagent". Inspired by the unique bis-heteroaryl structure of luciferin and 5
      heteroaryl-2'-deoxyuridine having good fluorescence properties, we designed and
      synthesized fluorogenic reagent 4,5-dimethoxy-2-aminothiophenol for a selective
      and convenient detection for 5-formyl-2'-deoxyuridine, which is generated in
      yields comparable to that of 2'-deoxy-8-oxoguanosine, in DNA. Generated 5-(5,6
      dimethoxybenzothiazol-2-yl)-2'-deoxyuridine has a high quantum yield and larger
      Stokes shift in aqueous solution. This derivatization of 5-formyl-2'-deoxyuridine
      in oligodeoxynucleotide occurred quickly and quantitatively. The fluorogenic
      reagent was also revealed to detect 5-formyl-2'-deoxyuridine in gamma-irradiated
      calf thymus DNA with irradiation dose dependent manner. Thus, our fluorogenic
      strategy enables to selective and convenient detection of lesion in DNA exposed
      to various forms of oxidative stress.

PMID- 24088350
TI  - [Synthetic studies on natural products with aromatic nitrogen heterocycles based
      on development of the methods for the formation of aryl carbon-nitrogen bond].
AB  - Total syntheses of yatakemycin, PDE-II, dictyodendrins, and heptaphylline are
      described. This article focuses on the formation of aryl carbon-nitrogen bonds by
      two methods: first by an aromatic amination reaction using a combination of CuI
      and CsOAc, and then by a benzyne-mediated one-pot cyclization-functionalization
      sequence. The aryl amination reaction shows a high functional group compatibility
      and applicability for highly hindered substrates. The utility of this reaction
      has been fully demonstrated through a total synthesis of yatakemycin, which
      features the regioselective ring opening of (S)-epichlorohydrin with 2,6
      dibromophenyllithium species and the efficient deprotection of benzyl groups of
      aryl benzyl ether with BCl3 in the presence of pentamethylbenzene. The copper
      mediated aryl amination reaction was applied to a one-pot double aryl amination
      for facile access to the highly substituted pyrroloindole skeleton, which led to
      a concise total synthesis of PDE-II. A highly efficient total synthesis of
      dictyodendrins A-E was accomplished by the development of a novel benzyne
      mediated one-pot indoline formation/cross-coupling sequence for the construction
      of a highly substituted key indoline intermediate. Peripheral substituents were
      introduced onto this intermediate in a modular fashion to complete the total
      synthesis of dictyodendrins A-E. The utility of the one-pot benzyne-mediated
      cyclization-functionalization reaction was demonstrated by the total synthesis of
      carbazole alkaloid, heptaphylline.

PMID- 24088349
TI  - [Oxidative stress-mediated chemical modifications to biomacromolecules: mechanism
      and implication of modifications to human skin keratins and angiotensin II].
AB  - Dysregulated production of reactive oxygen species (ROS) during oxidative stress
      has been associated with a number of inflammatory and age-related degenerative
      diseases. ROS can directly react with DNA to form oxidized DNA bases. Direct
      protein oxidation and carbonylation occur on certain amino acid residues
      resulting in various post-translational modifications. ROS can also initiate the
      formation of lipid hydroperoxides, which undergo homolytic decomposition to the
      alpha,beta-unsaturated aldehydic bifunctional electrophiles such as 4-oxo-2(E)
      nonenal (ONE) and 4-hydroxy-2(E)-nonenal (HNE). Intracellular generation of
      highly reactive aldehydes can then result in the formation of DNA and protein
      adducts. ONE-derived heptanone-etheno and HNE-derived propano DNA adducts have
      been detected and shown to be mutagenic in a variety of biological systems. In
      addition, ONE and HNE are involved in protein dysfunctions and altered gene
      regulations through the modification of amino acid residues and crosslinking of
      proteins. Our recent study on human skin keratins has identified specific K1
      methionine residues as the most susceptible sites to oxidation with hydrogen
      peroxide, which can be potential biomarkers of oxidative skin damage. The
      reactions of angiotensin (Ang) II with ONE or HNE produced several modified Ang
      IIs including a novel pyruvamide-Ang II that formed via oxidative decarboxylation
      of N-terminal aspartic acid. Subsequently, it has been revealed that the
      oxidative modifications on the N-terminus of Ang II disrupt interactions with Ang
      II type 1 receptor and aminopeptidase A, which could affect the regulation of
      cardiovascular function.

PMID- 24088352
TI  - [Development of Zn(2+) selective fluorescent probes for biological applications].
AB  - Zn(2+) is an essential element for life and is known to play important roles in
      biological processes including gene expression, apoptosis, enzyme regulation,
      immune system and neurotransmission. To investigate physiological roles of free
      or chelatable Zn(2+) in living cells, Zn(2+)-selective fluorescent probes are
      valuable tools. A variety of fluorescent probes based on quinoline, BF2 chelated
      dipyrromethene, fluorescein, etc. has been developed recently. In principle, such
      tools can provide useful information about zinc biology. However, most of the
      fluorescent probes presented so far possess a fluorescent core and a separate
      part for binding to Zn(2+) within the molecule, so that the molecular weight is
      usually large and the molecules are hydrophobic. As a result, the applications of
      such molecules in biological systems often face difficulties. Therefore, we need
      to develop a new class of fluorescent probes for Zn(2+) with improved molecular
      characteristics. If the initial core structure is small enough, the fluorescent
      probes may still be molecular weight below 500 with desirable physico-chemical
      properties, even after the modifications. In this review, we described novel low
      molecular-weight fluorescent probes for Zn(2+) based on pyridine-pyridone. Small
      modification of pyridine-pyridone core structure brought about a marked
      improvement such as aqueous solubility, affinity toward Zn(2+), and fluorescence
      ON/OFF switching. Fluorescence images of Zn(2+) in cells showed that the pyridine
      pyridone probe can be used in biological applications.

PMID- 24088351
TI  - [Personalized drug therapy-directed clinical pharmacology research based on
      genetic polymorphisms and pharmacokinetics analysis].
AB  - In this decade, the field of pharmacogenomics (PGx), which is related to
      pharmacokinetics (PK) or pharmacodynamics (PD), has attracted much attention
      because it may provide a possible explanation for individual differences in the
      clinical efficacy of drugs. For the development of personalized drug therapy, it
      is important to accumulate evidence from PK/PD/PGx analysis in clinical trials.
      Warfarin (WF) is one of the most widely prescribed anticoagulants for the
      prevention and treatment of venous and arterial thromboembolism. However, large
      interindividual and interethnic differences have been observed in the WF dose
      required to elicit the anticoagulant effect. We investigated the factors
      influencing the WF maintenance dose in Japanese patients. Our study confirmed a
      large interindividual variability in the WF maintenance dose that was due to a
      VKORC1 1639 G>A polymorphism and differences in body weight, age, and serum
      albumin. In addition, we found that the CYP4F2 genotype affects the plasma
      concentration of menaquinone-4, and that this finding was correlated with the WF
      sensitivity index in Japanese pediatric patients. Methotrexate (MTX) is an
      antifolate that is widely used to treat rheumatoid arthritis (RA) and cancer. The
      response to low-dose MTX demonstrated wide interpatient variability; however, the
      contributing factors remain unclear. We found that the frequency of the RFC1 80A
      allele was higher in RA patients treated with MTX alone compared with patients
      who received biological disease-modifying antirheumatic drugs (bDMARDs). This
      finding may support the combined use of bDMARDs and MTX. Further large-scale
      prospective clinical trials are required to confirm these findings.

PMID- 24088353
TI  - [Medicinal chemistry and pharmacology focused on cannabidiol, a major component
      of the fiber-type cannabis].
AB  - Considerable attention has focused on cannabidiol (CBD), a major non-psychotropic
      constituent of fiber-type cannabis plant, and it has been reported to possess
      diverse biological activities. Although CBD is obtained from non-enzymatic
      decarboxylation of its parent molecule, cannabidiolic acid (CBDA), several
      studies have investigated whether CBDA itself is biologically active. In the
      present report, the author summarizes findings indicating that; 1) CBDA is a
      selective cyclooxygenase-2 (COX-2) inhibitor, and ii) CBDA possesses an anti
      migrative potential for highly invasive cancer cells, apparently through a
      mechanism involving inhibition of cAMP-dependent protein kinase A, coupled with
      an activation of the small GTPase, RhoA. Further, the author introduces recent
      findings on the medicinal chemistry and pharmacology of the CBD derivative, CBD
      2',6'-dimethyl ether (CBDD), that exhibits inhibitory activity toward 15
      lipoxygenase (15-LOX), an enzyme responsible for the production of oxidized low
      density lipoprotein (LDL). These studies establish CBD as both an important
      experimental tool and as a lead compound for pharmaceutical development. In this
      review, the author further discusses the potential uses of CBD and its
      derivatives in future medicines.

PMID- 24088354
TI  - [Study of molecular function of proteins in human immunodeficiency virus].
AB  - Human immunodeficiency virus (HIV) has no more than nine genes expressing
      approximately twenty proteins. When T lymphocytes and macrophages in a body are
      infected with HIV, these proteins work in turn at specific time and location,
      causing acquired immunodeficiency syndrome (AIDS), a disease yet to be overcome.
      Since the elucidation of molecular mechanism of HIV proteins should lead to
      remedy of AIDS, the author has been engaged in the study of HIV protein in the
      past decade. Described herein are viral protein X (Vpx), uniquely found in HIV-2,
      and its homologous protein Vpr found both in HIV-1 and -2. We found that Vpx
      enhances genome nuclear import in T lymphocytes, and is critical for reverse
      transcription of viral RNA in macrophages. This finding on the function in
      macrophages corrected long-term misleading belief. Furthermore, functional region
      mapping of Vpx was performed. In 2011, the protein SAMHD1 was identified as the
      host restriction factor counteracted by Vpx, by foreign researchers. After that,
      our independent study demonstrated the presence of SAMHD1-independent functions
      of Vpx in T cells, in addition to its SAMHD1-dependent functions in macrophages.
      Another topic of this review is Gag protein. Recently, it has reported by
      overseas researchers that PI(4,5)P2 (one of phosphoinositide) regulates Pr55(Gag)
      localization and assembly. In this study, we determined the binding affinity
      between N-terminal MA domain of Pr55(Gag) and various phosphoinositide
      derivatives using surface plasmon resonance. The results suggested that both
      negatively charged inositol phosphates and hydrophobic acyl chain are required
      for the MA binding.

PMID- 24088355
TI  - [Polyethylene glycol accelerates loop-mediated isothermal amplification (LAMP)
      reaction].
AB  - Loop-mediated isothermal amplification (LAMP) has several advantages: this
      technique involves gene amplification under isothermal conditions using only one
      high-specificity enzyme; the amplification efficiency is so high that large
      quantities of pyrophosphoric acid are formed as a by-product of DNA synthesis;
      furthermore, the results can be judged directly on the basis of turbidity. On the
      other hand, a PCR requires approximately 3.5-4.0 hours. The LAMP method is faster
      than the PCR method and is also relatively inexpensive. In the present study, we
      modified the composition of the reaction solutions to reduce the LAMP reaction
      time; more specifically, a thickener, either polyethylene glycol 8000 or 20000,
      was added. These results showed that the LAMP method was faster than the original
      method, and it is able to detect both turbidity and fluorescence. In conclusion,
      the LAMP reaction could be performed within 20 minutes when reaction mixture
      supplemented with a thickener was used. This method can be used for tests in
      various fields such as the diagnosis of hereditary disease and identification of
      viral infections as point-of-care testing.

PMID- 24088356
TI  - [Effectiveness of Team-Based Learning (TBL) as a new teaching approach for
      pharmaceutical care education].
AB  - The concept of Team-Based Learning (TBL) was developed in the late 1970s by Larry
      Michaelsen, who wanted students to enjoy the benefits of small group learning
      within large classes in the business school environment. In contrast to problem
      based learning (PBL), which is student centered, TBL is typically instructor
      centered. Recently, TBL is being used as a teaching method in over 60 health
      science professional schools in the US and other countries. In the present study,
      the impact of adopting TBL in teaching pharmaceutical care practices to students
      was evaluated. Students were required to answer a set of multiple-choice
      questions individually in individual readiness assessment test (IRAT) before the
      TBL sessions to assess their level of preparation. The same set of questions was
      then reattempted by the group readiness assessment test (GRAT) during TBL.
      Comparing the scores obtained in the GRAT and IRAT before the first TBL session,
      the scores from the GRAT were always higher than those of the IRAT, indicating
      that TBL has encouraged active learning. In addition, students were surveyed
      about their level of satisfaction with TBL and written comments about TBL were
      solicited. The results of the questionnaire showed that 87.3+/-9.3% of the
      students were satisfied. Moreover, no student commented that TBL was in any way
      inferior to the PBL. Implementation of a TBL approach was successfully integrated
      into the pharmaceutical care education course. In order to further improve the
      usefulness of TBL in teaching pharmaceutical care, a hybrid teaching approach
      that also comprises PBL and a lecture-based course is desirable.

PMID- 24088357
TI  - The effects of levosimendan and dobutamine in experimental bupivacaine-induced
      cardiotoxicity.
AB  - BACKGROUND: Accidental intravenous exposure to bupivacaine is highly cardiotoxic
      and may lead to death. Positive inotropic agents are usually utilized in
      resuscitative efforts. We have compared the efficacy of levosimendan, a novel
      inotropic agent, with dobutamine and their combination in a rat model of
      bupivacaine intoxication. METHODS: Twenty-eight male Wistar albino rats weighing
      between 250-300 g were divided into these four groups: control (C), levosimendan
      (L), dobutamine (D) and dobutamine+levosimendan (D+L). Bupivacaine was
      administered at a dose of 3 mg/kg/min until cardiac arrest occurred or for 120
      min. ECG, heart rate, blood pressure, arterial blood gases, and end tidal CO2
      levels were monitored. Levosimendan was administered as a bolus of 12 MUg/kg for
      10 min and continued as an infusion at 0.3 MUg/kg/min. Dobutamine was infused at
      a dose of 3 MUg/kg/min. The time required for a 50% and 75% decrease in heart
      rate and blood pressure with a total time to cardiac arrest and bupivacaine dose
      for obtaining cardiac arrest were analyzed. RESULTS: Time periods for heart rate
      reductions of 50% and 75% were significantly longer in groups L (903, 1198 s), D
      (984, 1542 s) and L+D (1705, 3152 s) compared with the control group (345, 538 s
      p < 0.001). Median times to mean blood pressure reductions of 50% and 75% were
      399 - 504 s in the control group, 1005 -1204 s in group L, 685 - 1009 s in group
      D and 1544- 2982 s in group L+D, and the difference was significant compared with
      the control group. Median time duration to asystole was 703 s in the control
      group compared with 1385 s in group L, 1789 s in group D and 3557 s in group L+D.
      Time to cardiac arrest was significantly higher in all 3 study groups. It was
      also significantly higher in the L+D group compared with both groups L and D
      separately. CONCLUSION: A combination of dobutamine with levosimendan
      significantly increased survival times in this bupivacaine-induced toxicity rat
      model compared with the control, levosimendan, and dobutamine groups.

PMID- 24088358
TI  - First result of differentiated communication--to smokers and non-smokers--in
      order to increase the voluntary participation rate in lung screening.
AB  - BACKGROUND: Lung cancer is the most common fatal malignancy and also the primary
      cause of cancer mortality. Participation in lung screening is an important step
      in diagnosing patient in early stage and it can promise better outcomes. The aim
      of this preliminary study was to determinate the differences in the participation
      rate of smokers and non-smokers in lung cancer screening and to determine the
      communication strategies to increase the participation rate. METHODS: In the
      given period of time (from May to August 2012) out of 1426 people who
      participated in the lung screening program 1,060 adult volunteers (331 males and
      729 females, average age 54.0 +/- 9.3 years), completed fully and anonymously
      author's questionnaire that contained 28 questions. 25.7% of the respondents were
      smokers (n=272), 64.6% have never smoked, while 9.7% were former smokers.
      RESULTS: Mostly former smokers considered lung screening as an effective method
      for early detection of pulmonary diseases (86.4%). The most important source
      (41.0%) of information was the general practitioner. The participation rate of
      non-smokers is higher in lung screening than the ratio of non-smokers in the
      population. The unclear data suggest that smokers need distinct, concise messages
      to know why they should regularly undergo lung screening and doctors have a major
      role in this. CONCLUSIONS: We found that smokers significantly more frequently
      took part in lung screening annually. It is positive that the participation rate
      of former smokers is higher than non-smokers, it is just a bit lower than the
      participation rate of smokers--both in annual and biannual participation. The
      participation rate of non-smokers is higher in lung screening than the rate of
      non-smokers in the population.

PMID- 24088359
TI  - Comparative study of conventional surgery and internal intestinal splinting with
      long nasointestinal tube in the treatment of acute small bowel obstruction.
AB  - BACKGROUND/AIMS: To evaluate the application value of internal intestinal
      splinting with long nasointestinal tube in the treatment of acute small bowel
      obstruction. METHODOLOGY: Retrospective analysis of 129 cases, from Apr. 2005 to
      Dec. 2010 in the 3rd department of general surgery, First Affiliated Hospital of
      Dalian Medical University. There were 41 cases in treatment group (internal
      intestinal splinting with long nasointestinal tube) and 88 cases in control group
      (conventional SBO surgery). RESULTS: Postoperative timing of passing flatus and
      defecation time, the rate of postoperative complications and the postoperative
      mortality did not show any statistically significant difference between the two
      groups, (p >0.05); the 5 years recurrence rate of 4.88% (2/41) in the treatment
      group was obviously less than the 18.18% (16/88) of the control group, (p <0.05).
      The recurrence time in the treatment group was 42.50+/-7.78 months, obviously
      later than the control group 20.25+/-11.82 months, a statistically significant
      difference between the two groups (p <0.05). CONCLUSIONS: Compared with
      conventional acute SBO surgery, there is less recurrence rate and late recurrence
      time in the internal intestinal splinting with long nasointestinal tube group. It
      is an ideal treatment for acute small bowel obstruction.

PMID- 24088360
TI  - Developing content for a process-of-care checklist for use in intensive care
      units: a dual-method approach to establishing construct validity.
AB  - BACKGROUND: In the intensive care unit (ICU), checklists can be used to support
      the delivery of quality and consistent clinical care. While studies have reported
      important benefits for clinical checklists in this context, lack of formal
      validity testing in the literature prompted the study aim; to develop relevant
      'process-of-care' checklist statements, using rigorously applied and reported
      methods that were clear, concise and reflective of the current evidence base.
      These statements will be sufficiently instructive for use by physicians during
      ICU clinical rounds. METHODS: A dual-method approach was utilized; semi
      structured interviews with local clinicians; and rounds of surveys to an expert
      Delphi panel. The interviews helped determine checklist item inclusion/exclusion
      prior to the first round Delphi survey. The panel for the modified-Delphi
      technique consisted of local intensivists and a state-wide ICU quality committee.
      Minimum standards for consensus agreement were set prior to the distribution of
      questionnaires, and rounds of surveys continued until consensus was achieved.
      RESULTS: A number of important issues such as overlap with other initiatives were
      identified in interviews with clinicians and integrated into the Delphi
      questionnaire, but no additional checklist items were suggested, demonstrating
      adequate checklist coverage sourced from the literature. These items were
      verified by local clinicians as being relevant to ICU and important elements of
      care that required checking during ward rounds. Two rounds of Delphi surveys were
      required to reach consensus on nine checklist statements: nutrition, pain
      management, sedation, deep vein thrombosis and stress ulcer prevention, head-of
      bed elevation, blood glucose levels, readiness to extubate, and medications.
      CONCLUSIONS: Statements were developed as the most clear, concise, evidence
      informed and instructive statements for use during clinical rounds in an ICU.
      Initial evidence in support of the checklist's construct validity was established
      prior to further prospective evaluation in the same ICU.

PMID- 24088361
TI  - Saturable human neopterin response to interferon-alpha assessed by a
      pharmacokinetic-pharmacodynamic model.
AB  - BACKGROUND: In this study, we developed a pharmacokinetic (PK)- pharmacodynamic
      (PD) model of a new sustained release formulation of interferon-alpha-2a (SR-IFN
      alpha) using the blood concentration of IFN-alpha and neopterin in order to
      quantify the magnitude and saturation of neopterin production over time in
      healthy volunteers. The SR-IFN-alpha in this study is a solid microparticular
      formulation manufactured by spray drying of a feeding solution containing IFN
      alpha, a biocompatible polymer (polyethylene glycol) and sodium hyaluronate.
      METHODS: The full PK and PD (neopterin concentration) datasets from 24 healthy
      subjects obtained after single doses of 9, 18, 27 and 36 MIU of subcutaneous SR
      IFN-alpha were used to build the mixed-effect model using NONMEM (version 7.2)
      with the GFORTRAN compiler. RESULTS: A one-compartment model with first-order
      elimination and a mixture of zero- and first-order absorption was chosen to
      describe the PK of SR-IFN-alpha. The time-concentration profile of neopterin, the
      PD marker, was described by a turnover model combined with a single transit
      compartment. The saturable pattern of the neopterin response blurring the dose
      response relationship of SR-IFN-alpha was addressed by introducing the concept of
      the EC50 increasing over time. CONCLUSIONS: The PK-PD model of SR-IFN-alpha
      developed in this study has presented a quantitative tool to assess the time
      course of a saturable neopterin response in humans.

PMID- 24088362
TI  - Compliance to advanced trauma life support protocols in adult trauma patients in
      the acute setting.
AB  - INTRODUCTION: Advanced Trauma Life Support (ATLS) protocols provide a common
      approach for trauma resuscitations. This was a quality review assessing
      compliance with ATLS protocols at a Level I trauma center; specifically whether
      the presence or absence of a trauma team leader (TTL) influenced adherence.
      METHODS: This retrospective study was conducted on adult major trauma patients
      with acute injuries over a one-year period in a Level I Canadian trauma center.
      Data were collected from the Alberta Trauma Registry, and adherence to ATLS
      protocols was determined by chart review. RESULTS: The study identified 508
      patients with a mean Injury Severity Score of 24.5 (SD 10.7), mean age 39.7 (SD
      17.6), 73.8% were male and 91.9% were involved in blunt trauma. The overall
      compliance rate was 81.8% for primary survey and 75% for secondary survey. The
      TTL group compared to non-TTL group was more likely to complete the primary
      survey (90.9% vs. 81.8%, p = 0.003), and the secondary survey (100% vs. 75%, p =
      0.004). The TTL group was more likely than the non-TTL group to complete the
      following tasks: insertion of two large bore IVs (68.2% vs. 57.7%, p = 0.014),
      digital rectal exam (64.6% vs. 54.7%, p = 0.023), and head to toe exam (77% vs.
      67.1%, p = 0.013). Mean times from emergency department arrival to diagnostic
      imaging were also significantly shorter in the TTL group compared to the non-TTL
      group, including times to pelvis xray (mean 68min vs. 107min, p = 0.007), CT
      chest (mean 133min vs. 172min, p = 0.005), and CT abdomen and pelvis (mean 136min
      vs. 173min, p = 0.013). Readmission rates were not significantly different
      between the TTL and non-TTL groups (3.5% vs. 4.5%, p = 0.642). CONCLUSIONS: While
      many studies have demonstrated the effectiveness of trauma systems on outcomes,
      few have explored the direct influence of the TTL on ATLS compliance. This study
      demonstrated that TTL involvement during resuscitations was associated with
      improved adherence to ATLS protocols, and increased efficiency (compared to non
      TTL involvement) to diagnostic imaging. Findings from this study will guide
      future quality improvement and education for early trauma management.

PMID- 24088363
TI  - Cerebellar cavernous malformations with and without associated developmental
      venous anomalies.
AB  - BACKGROUND: The clinical profiles of cerebellar cavernous malformations (CCMs)
      with and without associated developmental venous anomalies (DVAs) are not well
      known. The aims of this study were to analyze the clinical and radiological
      characteristics of CCMs and to assess the various therapeutic strategies.
      METHODS: A consecutive series of 41 patients with identified CCMs were
      retrospectively reviewed. Of these, 11 patients (26.8%) were found to have
      associated DVAs. We compared the clinical profile of the two groups of patients
      (CCMs with and without DVAs). The CCMs with DVAs cases underwent radical
      resection of the CCMs, and the distal radicles of the DVAs that directly drain
      from the CCMs were coagulated and dissected at the length of the CCMs. RESULTS:
      There were no statistically significant differences between the two groups with
      regard to age, sex, location and size of lesions, multiplicity, and surgical
      prognosis. The patients with CCMs with DVAs did not experience any brain swelling
      or hemorrhagic tendency intraoperatively. The postoperative course was uneventful
      for all of the 36 surgical patients with the exception of two of the patients
      with CCMs with associated DVAs, who suffered from serious cerebellar edema, and
      one of these two patients underwent an emergency suboccipital decompression
      craniotomy. With the exception of three patients who were lost to follow-up
      (mean, 22.3 months), all of the CCMs patients exhibited good long-term prognosis
      (modified Rankin scale values of 0-2) and no reoccurrence. CONCLUSIONS: It is not
      rare that associated DVAs occur in CCMs. The total removal of the CCM combined
      with the coagulation and dissection of the distal radicles of DVA at the length
      of the associated CCM may result in good long-term prognosis in patients.

PMID- 24088364
TI  - Global mental health: transformative capacity building in Nicaragua.
AB  - BACKGROUND: Mental health is increasingly recognised as integral to good public
      health, but this area continues to lack sufficient planning, resources, and
      global strategy. It is a pressing concern in Latin America, where social
      determinants of health aggravate existing inequities in access to health
      services. Nicaragua faces serious mental health needs and challenges. One key
      strategy for addressing gaps in mental health services is building capacity at
      the primary healthcare and system levels. OBJECTIVE: Using the framework of best
      practice literature, this article analyses the four-year collaborative process
      between the National Autonomous University of Nicaragua in Leon (UNAN-Leon) and
      the Centre for Addiction and Mental Health (CAMH) in Canada, which is aimed at
      improving mental healthcare in Nicaragua. DESIGN: Based on a critical analysis of
      evaluation reports, key documents, and discussion among partners, the central
      steps of the collaboration are analysed and main successes and challenges
      identified. RESULTS: A participatory needs assessment identified local strengths
      and weaknesses, expected outcomes regarding competencies, and possible
      methodologies and recommendations for the development of a comprehensive capacity
      building programme. The partners delivered two international workshops on mental
      health and addiction with an emphasis on primary healthcare. More recently, an
      innovative Diploma and Master programme was launched to foster interprofessional
      leadership and effective action to address mental health and addiction needs.
      Collaborative activities have taken place in Nicaragua and Canada. DISCUSSION: To
      date, international collaboration between Nicaragua and CAMH has been successful
      in achieving the jointly defined goals. The process has led to mutual knowledge
      sharing, strong networking, and extensive educational opportunities. Evidence of
      effective and respectful global health capacity building is provided. Lessons
      learned and implications for global health action are identified and discussed.

PMID- 24088365
TI  - Development of SNP markers for genes of the phenylpropanoid pathway and their
      association to kernel and malting traits in barley.
AB  - BACKGROUND: Flavonoids are an important class of secondary compounds in
      angiosperms. Next to certain biological functions in plants, they play a role in
      the brewing process and have an effect on taste, color and aroma of beer. The aim
      of this study was to reveal the haplotype diversity of candidate genes involved
      in the phenylpropanoid biosynthesis pathway in cultivated barley varieties
      (Hordeum vulgare L.) and to determine associations to kernel and malting quality
      parameters. RESULTS: Five genes encoding phenylalanine ammonia-lyase (PAL),
      cinnamate 4-hydroxylase (C4H), chalcone synthase (CHS), flavanone 3-hydroxylase
      (F3H) and dihydroflavonol reductase (DFR) of the phenylpropanoid biosynthesis
      pathway were partially resequenced in 16 diverse barley reference genotypes.
      Their localization in the barley genome, their genetic structure, and their
      genetic variation e.g. single nucleotide polymorphism (SNP) and
      Insertion/Deletion (InDel) patterns were revealed. In total, 130 SNPs and seven
      InDels were detected. Of these, 21 polymorphisms were converted into high
      throughput pyrosequencing markers. The resulting SNP and haplotype patterns were
      used to calculate associations with kernel and malting quality parameters.
      CONCLUSIONS: SNP patterns were found to be highly variable for the investigated
      genes. The developed high-throughput markers are applicable for assessing the
      genetic variability and for the determination of haplotype patterns in a set of
      barley accessions. The candidate genes PAL, C4H and F3H were shown to be
      associated to several malting properties like glassiness (PAL), viscosity (C4H)
      or to final attenuation (F3H).

PMID- 24088366
TI  - Challenges and needs for China to eliminate rabies.
AB  - In China, rabies is a significant public health concern where dogs remain the
      main reservoir of disease transmission to humans; rabies-related mortality ranks
      second in the world.We compiled all published articles and official documents on
      rabies in mainland China to examine challenges and needs to eliminate rabies in
      the country. The Chinese authorities have identified rabies as a priority,
      recognized rabies control in dogs as key to control rabies in humans and required
      intersectoral collaborations. Efforts have been made to respond effectively to
      the latest re-emergence of rabies, which peaked in 2007 with >3,300 cases.
      Despite these outcomes and the increasing volume of publications and regulations
      in the recent years, our review points to some major information gaps to improve
      rabies control activities and envisage elimination program. An emphasis on
      laboratory or pathogen-associated and basic epidemiology research in the
      literature has contrasted with the absence of information to monitor various
      systems in humans and animals (e.g. quality of surveillance, response and post
      exposure prophylaxis). Information is also lacking to appropriately inform
      policymakers (e.g. economic disease burden, impact of policies) and assist
      program managers (e.g. comprehensive and strategic guidance for cost-effective
      prevention and control activities, public education and dog population
      management).In conclusion, strategic planning is needed to provide a sense of
      direction, demonstrate feasibility of elimination in China, and develop a
      research agenda, addressing country's operational needs and constraints. The
      planning should be a multisectoral effort. 

PMID- 24088367
TI  - The Emergency Severity Index, version 4, for pediatric triage: a reliability
      study in Tabriz Children's Hospital, Tabriz, Iran.
AB  - BACKGROUND: The Emergency Severity Index (ESI) has earned reliability and
      validity in adult populations but has not been adequately evaluated in pediatric
      patients. The aim of this study was to assess the reliability of the ESI version
      4 and inter-rater reliability measures to evaluate the performance of nurses in
      the emergency ward. METHODS: Raters were part of the same team of pediatric
      emergency medicine team, including pediatric emergency medicine (PEM) physicians
      and pediatric triage (PT) nurses. Reliability and agreement rates were measured
      using kappa statistics. The measurements were compared with the admission rates,
      readmissions to the PEM division, location of admission and death as outcomes.
      RESULTS: Initially, PT nurses rated 20 case scenarios. Further in a prospective
      cohort study, 1104 children were assigned ESI scores by both nurses and
      physicians. The ratings of case scenarios showed a kappa value of 0.84. In actual
      patients, ratings showed high concordance with the physicians' ratings with the
      kappa value of 0.82 being in a good agreement with the nurses' ratings. The main
      area of discordance was detected in level 4 where 48 cases were triaged in higher
      levels and 25 were triaged in lower levels. The analysis showed the likelihood of
      admission clearly increased as the ESI score decreased (p<0.0001). There was a
      significant correlation between the admission status and triage level in both PT
      nurses' and PEM physicians' ratings (Spearman coefficient=0.374, 0.407;
      p<0.0001). CONCLUSION: ESI scores assigned to the pediatric patients are reliable
      in the hands of experienced PT nurses and PEM physicians. The very good agreement
      between PT nurses and PEM physicians, demonstrated in this study, is essential in
      cooperative work in crowded referral emergency departments and helpful in
      challenging triage cases.

PMID- 24088368
TI  - Glycaemic control in Australia and New Zealand before and after the NICE-SUGAR
      trial: a translational study.
AB  - INTRODUCTION: There is no information on the uptake of Intensive Insulin Therapy
      (IIT) before the Normoglycemia in Intensive Care Evaluation and Surviving Using
      Glucose Algorithm Regulation (NICE-SUGAR) trial in Australia and New Zealand
      (ANZ) and on the bi-national response to the trial, yet such data would provide
      important information on the evolution of ANZ practice in this field. We aimed to
      study ANZ glycaemic control before and after the publication of the results of
      the NICE-SUGAR trial. METHODS: We analysed glucose control in critically ill
      patients across Australia and New Zealand during a two-year period before and
      after the publication of the NICE-SUGAR study. We used the mean first day glucose
      (Glu1) (a validated surrogate of ICU glucose control) to define practice. The
      implementation of an IIT protocol was presumed if the median of Glu1 measurements
      was <6.44 mmol/L for a given ICU. Hypoglycaemia was categorised as severe
      (glucose <=2.2 mmol/L) or moderate (glucose <=3.9 mmol/L). RESULTS: We studied 49
      ICUs and 176,505 patients. No ICU practiced IIT before or after NICE-SUGAR.
      Overall, Glu1 increased from 7.96 (2.95) mmol/L to 8.03 (2.92) mmol/L (P <0.0001)
      after NICE-SUGAR. Similar increases were noted in all patient subgroups studied
      (surgical, medical, insulin dependent diabetes mellitus, ICU stay >48/<48 hours).
      The rate of severe and moderate hypoglycaemia before and after NICE-SUGAR study
      were 0.59% vs. 0.55% (P =0.33) and 6.62% vs. 5.68% (P <0.0001), respectively.
      Both crude and adjusted mortalities declined over the study period. CONCLUSIONS:
      IIT had not been adopted in ANZ before the NICE-SUGAR study and glycaemic control
      corresponded to that delivered in the control arm of NICE-SUGAR trial. There were
      only minor changes in practice after the trial toward looser glycaemic control.
      The rate of moderate hypoglycaemia and mortality decreased along with such
      changes.

PMID- 24088369
TI  - Posttraumatic growth, posttraumatic stress and psychological adjustment in the
      aftermath of the 2011 Oslo bombing attack.
AB  - BACKGROUND: Experiencing potentially traumatic events is associated with
      psychological distress. However, some survivors also experience positive personal
      and psychological changes in the aftermath of trauma. METHODS: The present study
      investigated perceived posttraumatic growth in 197 ministerial employees who were
      present at work during the 2011 Oslo bombing attack. The relationships between
      trauma-exposure, peritraumatic reactions and posttraumatic growth were studied.
      Moreover, the adaptive significance of posttraumatic growth was addressed.
      RESULTS: The results showed that higher levels of trauma-exposure and immediate
      reactions were significantly related to perceived posttraumatic growth. No
      support for an adaptive significance of posttraumatic growth was found. On the
      contrary, posttraumatic growth was associated with higher symptom levels of
      posttraumatic stress. After adjusting for posttraumatic stress symptoms no
      association was found between perceived growth and work and social adjustment.
      However, perceived growth was associated with higher levels of life satisfaction.
      CONCLUSION: The present results are in line with previous findings indicating
      that perceived growth may be unrelated to psychological adjustment, and suggest
      that the concept and significance of posttraumatic growth should be interpreted
      with caution.

PMID- 24088371
TI  - Building predictive models for mechanism-of-action classification from phenotypic
      assay data sets.
AB  - Compound mechanism-of-action information can be critical for drug development
      decisions but is often challenging for phenotypic drug discovery programs. One
      concern is that compounds selected by phenotypic screening will have a previously
      known but undesirable target mechanism. Here we describe a useful method for
      assigning mechanism class to compounds and bioactive agents using an 84-feature
      signature from a panel of primary human cell systems (BioMAP systems). For this
      approach, a reference data set of well-characterized compounds was used to
      develop predictive models for 28 mechanism classes using support vector machines.
      These mechanism classes encompass safety and efficacy-related mechanisms, include
      both target-specific and pathway-based classes, and cover the most common
      mechanisms identified in phenotypic screens, such as inhibitors of mitochondrial
      and microtubule function, histone deacetylase, and cAMP elevators. Here we
      describe the performance and the application of these predictive models in a
      decision scheme for triaging phenotypic screening hits using a previously
      published data set of 309 environmental chemicals tested as part of the
      Environmental Protection Agency's ToxCast program. By providing quantified
      membership in specific mechanism classes, this approach is suitable for
      identification of off-target toxicity mechanisms as well as enabling target
      deconvolution of phenotypic drug discovery hits. 

PMID- 24088370
TI  - Development of a high-throughput AlphaScreen assay for modulators of synapsin I
      phosphorylation in primary neurons.
AB  - Alterations in synaptic transmission have been implicated in a number of
      psychiatric and neurological disorders. The discovery of small-molecule
      modulators of proteins that regulate neurotransmission represents a novel
      therapeutic strategy for these diseases. However, high-throughput screening (HTS)
      approaches in primary neurons have been limited by challenges in preparing and
      applying primary neuronal cultures under conditions required for generating
      sufficiently robust and sensitive HTS assays. Synapsin I is an abundant
      presynaptic protein that plays a critical role in neurotransmission through
      tethering synaptic vesicles to the actin cytoskeleton. It has several
      phosphorylation sites that regulate its modulation of synaptic vesicle
      trafficking and, therefore, the efficacy of synaptic transmission. Here, we
      describe the development of a rapid, sensitive, and homogeneous assay to detect
      phospho-synapsin I (pSYN1) in primary cortical neurons in 384-well plates using
      AlphaScreen technology. From results of a pilot screening campaign, we show that
      the assay can identify compounds that modulate synapsin I phosphorylation via
      multiple signaling pathways. The implementation of the AlphaScreen pSYN1 assay
      and future development of additional primary neuronal HTS assays provides an
      attractive approach for discovery of novel classes of therapeutic candidates for
      a variety of CNS disorders. 

PMID- 24088373
TI  - Quantum resistance metrology using graphene.
AB  - In this paper, we review the recent extraordinary progress in the development of
      a new quantum standard for resistance based on graphene. We discuss the unique
      properties of this material system relating to resistance metrology and discuss
      results of the recent highest-ever precision direct comparison of the Hall
      resistance between graphene and traditional GaAs. We mainly focus our review on
      graphene expitaxially grown on SiC, a system which so far resulted in the best
      results. We also briefly discuss progress in the two other graphene material
      systems, exfoliated graphene and chemical vapour deposition graphene, and make a
      critical comparison with SiC graphene. Finally, we discuss other possible
      applications of graphene in metrology. 

PMID- 24088374
TI  - Delivery of occupational and environmental health services.

PMID- 24088372
TI  - Nanotoxicity comparison of four amphiphilic polymeric micelles with similar
      hydrophilic or hydrophobic structure.
AB  - BACKGROUND: Nanocarriers represent an attractive means of drug delivery, but
      their biosafety must be established before their use in clinical research.
      OBJECTIVES: Four kinds of amphiphilic polymeric (PEG-PG-PCL, PEEP-PCL, PEG-PCL
      and PEG-DSPE) micelles with similar hydrophilic or hydrophobic structure were
      prepared and their in vitro and in vivo safety were evaluated and compared.
      METHODS: In vitro nanotoxicity evaluations included assessments of cell
      morphology, cell volume, inflammatory effects, cytotoxicity, apoptosis and
      membrane fluidity. An umbilical vein cell line (Eahy.926) and a kind of
      macrophages (J774.A1) were used as cell models considering that intravenous route
      is dominant for micelle delivery systems. In vivo analyses included complete
      blood count, lymphocyte subset analysis, detection of plasma inflammatory factors
      and histological observations of major organs after intravenous administration to
      KM mice. RESULTS: All the micelles enhanced inflammatory molecules in J774.A1
      cells, likely resulting from the increased ROS levels. PEG-PG-PCL and PEEP-PCL
      micelles were found to increase the J774.A1 cell volume. This likely correlated
      with the size of PEG-PG-PCL micelles and the polyphosphoester structure in PEEP
      PCL. PEG-DSPE micelles inhibited the growth of Eahy.926 cells via inducing
      apoptosis. This might relate to the structure of DSPE, which is a type of
      phospholipid and has good affinity with cell membrane. No evidence was found for
      cell membrane changes after treatment with these micelles for 24 h. In the in
      vivo study, during 8 days of 4 time injection, each of the four nanocarriers
      altered the hematic phase differently without changes in inflammatory factors or
      pathological changes in target organs. CONCLUSIONS: These results demonstrate
      that the micelles investigated exhibit diverse nanotoxicity correlated with their
      structures, their biosafety is different in different cell model, and there is no
      in vitro and in vivo correlation found. We believe that this study will certainly
      provide more scientific understandings on the nanotoxicity of amphiphilic
      polymeric micelles.

PMID- 24088375
TI  - Effects of a brief pilot sexual harassment prevention workshop on employees'
      knowledge.
AB  - Administrators from three workplaces were interested in conducting evidence-based
      sexual harassment prevention training for their employees, but they could devote
      little time during the workday to the training. A pilot program to evaluate the
      use of a 1-hour workshop that followed best practice recommendations and adult
      learning principles using job-related scenarios was designed. Participants'
      overall sexual harassment prevention knowledge scores significantly increased
      from before to after the workshop and were significantly higher after the
      workshop than those of a control group. The majority of participants also
      perceived that their workplaces were committed to employees understanding the
      sexual harassment policy, and that the workplace would seriously investigate
      claims and take corrective action. Even a brief workshop covering essential
      content using adult learning principles can be effective in sexual harassment
      prevention knowledge acquisition.

PMID- 24088377
TI  - Energy drinks and worker health risks.
AB  - Occupational and environmental health nurses play a key role in raising
      awareness, advocating for public health and safety, and preventing deleterious
      health consequences for individuals who consume energy drinks.

PMID- 24088378
TI  - Non-neoplastic bulky mediastinal mass presentation in an adolescent patient: a
      case report.
AB  - INTRODUCTION: Mediastinal masses in pediatric patients are very heterogeneous in
      origin and etiology. In the first decade of life, 70% of the mediastinal masses
      are benign whereas malignant tumors are more frequent in the second decade of
      life. Among the mediastinal masses, lymph nodes are the most common involved
      structures and could be enlarged due to a lymphoma, leukemia, metastatic disease,
      or due to infectious diseases as sarcoidosis, tuberculosis and others. CASE
      PRESENTATION: We report a case of a 13-year-old Caucasian girl who came to the
      emergency room with a history of intermittent fever, weight loss and night
      sweating for at least 1 month. A radiologic image work-up presented an anterior
      and posterior mediastinal mass. The 18F-fluorodeoxyglucose positron emission
      tomography presented a high maximum standard uptake value, which directed our
      decision for mediastinal biopsy for diagnostic elucidation. Histologic
      examination described the mass as granulomatous tuberculosis. The patient was
      treated with anti-tuberculosis therapy and developed a full clinical recovery.
      CONCLUSIONS: The present case report demonstrates that a bulky mediastinal
      lymphadenopathy detected on 18F-fluorodeoxyglucose positron emission tomography
      is not always a malignant lesion, and in countries where tuberculosis is endemic,
      this etiology should not be forgotten during clinical investigations. There is a
      need for more accurate cut-off values for this technology; meanwhile, the further
      investigation of patients with bulky mediastinal masses with procedures such as
      the open biopsy is indispensable.

PMID- 24088379
TI  - Running economy during a simulated 60-km trial.
AB  - The effect of a prolonged running trial on the energy cost of running (C(r))
      during a 60-km ultramarathon simulation at the pace of a 100-km competition was
      investigated in 13 men (40.8 +/- 5.6 y, 70.7 +/- 5.5 kg, 177.5 +/- 4.5 cm) and 5
      women (40.4 +/- 2.3 y, 53.7 +/- 4.4 kg, 162.4 +/- 4.8 cm) who participated in a
      60-km trial consisting of 3 consecutive 20-km laps. Oxygen uptake (VO(2)) at
      steady state was determined at constant speed before the test and at the end of
      each lap; stride length (SL) and frequency and contact time were measured at the
      same time points; serum creatine kinase (S-CPK) was measured before and at the
      end of the test. C(r) in J . kg(-1) . m(-1), as calculated from VO(2ss) and
      respiratory-exchange ratio, did not increase with distance. SL significantly
      decreased with distance. The net increase in S-CPK was linearly related with the
      percentage increase of C(r) observed during the trial. It is concluded that, in
      spite of increased S-CPK, this effort was not able to elicit any peripheral or
      central fatigue or biomechanical adaptation leading to any modification of C(r).

PMID- 24088381
TI  - The impact of the UK 'Act FAST' stroke awareness campaign: content analysis of
      patients, witness and primary care clinicians' perceptions.
AB  - BACKGROUND: The English mass media campaign 'Act FAST' aimed to raise stroke
      awareness and the need to call emergency services at the onset of suspected
      stroke. We examined the perceived impact and views of the campaign in target
      populations to identify potential ways to optimise mass-media interventions for
      stroke. METHODS: Analysis of semi-structured interviews conducted as part of two
      qualitative studies, which examined factors influencing patient/witness response
      to acute stroke symptoms (n = 19 stroke patients, n = 26 stroke witnesses) and
      perceptions about raising stroke awareness in primary care (n = 30 clinicians).
      Both studies included questions about the 'Act FAST' campaign. Interviews were
      content analysed to determine campaign awareness, perceived impact on decisions
      and response to stroke, and views of the campaign. RESULTS: Most participants
      were aware of the Act FAST campaign. Some patients and witnesses reported that
      the campaign impacted upon their stroke recognition and response, but the
      majority reported no impact. Clinicians often perceived campaign success in
      raising stroke awareness, but few thought it would change response behaviours.
      Some patients and witnesses, and most primary care clinicians expressed positive
      views towards the campaign. Some more critical participant comments included
      perceptions of dramatic, irrelevant, and potentially confusing content, such as a
      prominent 'fire in the brain' analogy. CONCLUSIONS: Act FAST has had some
      perceived impact on stroke recognition and response in some stroke patients and
      witnesses, but the majority reported no campaign impact. Primary care clinicians
      were positive about the campaign, and believed it had impacted on stroke
      awareness and recognition but doubted impact on response behaviour. Potential
      avenues for optimising and complementing mass media campaigns such as 'Act FAST'
      were identified.

PMID- 24088382
TI  - The AKT inhibitor AZD5363 is selectively active in PI3KCA mutant gastric cancer,
      and sensitizes a patient-derived gastric cancer xenograft model with PTEN loss to
      Taxotere.
AB  - INTRODUCTION: Activation of the PI3K/AKT pathway is a common phenomenon in cancer
      due to multiple mechanisms, including mutation of PI3KCA, loss or mutation of
      PTEN, or over-expression of receptor tyrosine kinases. We recently developed a
      novel AKT kinase inhibitor, AZD5363, and demonstrated that HGC27, a cell line
      harboring both PI3KCA mutation and PTEN loss, displayed the greatest sensitivity
      to this AKT inhibitor in vitro and in vivo. CASE PREPARATION: To further
      elucidate the correlation between AZD5363 response and genetic alterations in
      gastric cancer (GC) and identify GC patients with both PI3KCA mutations and PTEN
      loss, we investigated the effects of pharmacological inhibition of AKT on a panel
      of 20 GC cell lines and genetic aberrations in tumor samples from a cohort of
      Chinese GC patients. We demonstrated that GC cells with PI3KCA mutations were
      selectively sensitive to AZD5363. Disease linkage studies showed that PI3KCA
      activating mutations or PTEN loss were found in 2.7% (4/150) and 23% (14/61) of
      Chinese GC patients respectively. To further dissect the role of PI3KCA mutation
      and PTEN loss in response to AKT inhibition, we tested the antitumor activity of
      AZD5363 in two patient-derived GC xenograft (PDGCX) models harboring either
      PI3KCA mutation or PTEN loss. Our data indicated that AZD5363 monotherapy
      treatment led to a moderate response in the PI3KCA mutant PDGCX model. Whilst
      monotherapy AZD5363 or Taxotere were ineffective in the PTEN negative PDGCX
      model, significant anti-tumor activity was observed when AZD5363 was combined
      with Taxotere. CONCLUSION: Our results indicated that PI3KCA mutation is an
      important determinant of response to AKT inhibition in GC and combination with
      AZD5363 can overcome innate resistance to Taxotere in a PTEN loss PDGCX model. It
      is suggested that AKT inhibitor is an attractive option for treatment of a new
      segment of GC patients with aberrant PI3K/AKT signaling.

PMID- 24088383
TI  - The transition of childbirth practices among tribal women in Gujarat, India - a
      grounded theory approach.
AB  - BACKGROUND: Under the National Rural Health Mission, the current emphasis is on
      achieving universal institutional births through incentive schemes as part of
      reforms related to childbirth in India. There has been rapid progress in
      achieving this goal. To understand the choices made as well as practices and
      perceptions related to childbirth amongst tribal women in Gujarat and how these
      have been influenced by modernity in general and modernity brought in through
      maternal health policies. METHOD: A model depicting the transition in childbirth
      practices amongst tribal women was constructed using the grounded theory approach
      with; 8 focus groups of women, 5 in depth interviews with traditional birth
      attendants, women, and service providers and field notes on informal discussions
      and observations. RESULTS: A transition in childbirth practices across
      generations was noted, i.e. a shift from home births attended by Traditional
      Birth Attendants (TBAs) to hospital births. The women and their families both
      adapted to and shaped this transition through a constant 'trade-off between
      desirable and essential'- the desirable being a traditional homebirth in secure
      surroundings and the essential being the survival of mother and baby by going to
      hospital. This transition was shaped by complex multiple factors: 1) Overall
      economic growth and access to modern medical care influencing women's choices, 2)
      External context in terms of the international maternal health discourses and
      national policies, especially incentive schemes for promoting institutional
      deliveries, 3) Socialisation into medical childbirth practices, through exposure
      to many years of free outreach services for maternal and child health, 4) Loss of
      self reliance in the community as a consequence of role redefinition and
      deskilling of the TBAs and 5) Cultural belief that intervention is necessary
      during childbirth aiding easy acceptance of medical interventions. CONCLUSION: In
      resource poor settings where choices are limited and mortality is high, hospital
      births are perceived as increasing the choices for women, saving lives of mothers
      and babies, though there is a need for region specific strategies. Modern
      obstetric technology is utilised and given meanings based on socio-cultural
      conceptualisations of birth, which need to be considered while designing policies
      for maternal health.

PMID- 24088384
TI  - Short tandem repeats in the inhibitory domain of the mineralocorticoid receptor:
      prediction of a beta-solenoid structure.
AB  - BACKGROUND: The human mineralocorticoid receptor (MR) is one of the main
      components of the renin-angiotensin-aldosterone system (RAAS), the system that
      regulates the body exchange of water and sodium. The evolutionary origins of this
      protein predate those of renin and the RAAS; accordingly it has other roles,
      which are being characterized. The MR has two trans-activating ligand independent
      domains and one inhibitory domain (ID), which modulates the activity of the
      former. The structure of the ID is currently unknown. RESULTS: Here we report
      that the ID contains at least 15 tandem repeats of around 10 amino acids, which
      we computationally characterize in the human MR and in selected orthologs. This
      ensemble of repeats seems to have emerged around 450 million years ago, after the
      divergence of the MR from its close homolog, the glucocorticoid receptor, which
      does not possess the repeats. The region would have quickly expanded by
      successive duplication of the repeats stabilizing at its length in human MR
      shortly after divergence of tetrapoda from bony fishes 400 million years ago.
      Structural predictions, in combination with molecular dynamics simulations
      suggest that the repeat ensemble forms a beta-solenoid, namely a beta-helical
      fold with a polar core, stabilized by hydrogen-bonded ladders of polar residues.
      Our 3D-model, in conjunction with previous experimental data, implies a role of
      the beta-helical fold as a scaffold for multiple intra-and inter-molecular
      interactions and that these interactions are modulated via phosphorylation
      dependent conformational changes. CONCLUSIONS: We, thus, propose that the
      structure of the repeat ensemble plays an important role in the coordination and
      sequential interactions of various MR partners and therefore in the functionality
      and specificity of MR.

PMID- 24088385
TI  - Low COST surgery setting for one-operational port laparoscopic hysterectomy
      surgery with ordinary laparoscopic instruments: preliminary results.
AB  - BACKGROUND: Hysterectomy dates back to 120BC and is the second most commonly
      performed gynecological surgery in the world. Cosmetic demands and the necessity
      of rapid return to work have contributed to the minimally invasive laparoscopic
      approach for hysterectomy. The majority of reports describe the use of three or
      four incisions to perform the surgery (two or three for manipulation and one for
      optics). METHODS: This work describes our experience with using only two ports
      for 11 patients who underwent video-laparoscopic hysterectomy surgery. One port
      was used for the optical system, and the second was used for manipulation. Early
      and late surgery complications, as well as the time to return to work and daily
      activities, were assessed. RESULTS: The mean age of the patients was 41.4 years
      old (range 16 to 52 years) and the mean uterine weight was 133.54 g, ranging from
      35 g and 291 g. The operative time ranged from 30 to 60 minutes (average 46.4
      minutes) and the hospital stay ranged between 24 and 48 hrs. No intraoperative
      complications occurred, and no early or late postoperative complications were
      recorded. Patients reported minimal pain during the first 24-48 hrs in the
      hospital. Patients returned to their daily activities within seven days after
      surgery. Clinical care follow-up continued until the 40th postoperative day.
      CONCLUSION: The laparoscopic hysterectomy technique with a single port for
      manipulation is a feasible procedure when the uterine weight is not greater than
      400 mg with little postoperative pain. The patients had an early return-to-work
      and daily activities and a better cosmetic outcome. These preliminary data led us
      to make the one-operative port laparoscopic hysterectomy the procedure of choice
      for patients with a low uterine weight.

PMID- 24088386
TI  - Probable medications overuse headaches: validation of a brief easy-to-use
      screening tool in a headache centre.
AB  - BACKGROUND: To validate a rapid questionnaire as a screening tool, because
      application of the diagnostic revised criteria of the ICHD-II for medication
      overuse headache (MOH) requires experience for the physician and is time
      consuming. METHODS: ICHD-II criteria for probable MOH (pMOH) were transformed in
      questions formulated in such a way that they could be self-administered, easily
      understood, and quickly filled out. We compared this questionnaire to the gold
      standard: the diagnosis made by headache specialists, based on the the ICHD-II
      criteria. Patients who were consulting for pMOH or migraine for the first time
      were consecutively included. As validity indicators, we calculated sensitivity,
      specificity, positive and negative predictive values of the items. RESULTS:
      Seventy-nine patients were screened, 77 included, 2 female patients excluded.
      Forty-two patients have been considered as suffering from pMOH, 35 patients
      suffered from migraine without medication overuse. The association of the
      question "do you take a treatment for attacks more than 10 days per month" and
      the question "is this intake on a regular basis?" had a sensitivity of 95.2% and
      a specificity of 80%. CONCLUSION: This screening tool can detect pMOH with a
      sensitivity that could be of interest to screen patients in clinical practice and
      to pre-include patients for research as epidemiological studies.

PMID- 24088387
TI  - Impact of the implementation of an online network support tool among clinicians
      of primary health care and specialists: ECOPIH Project.
AB  - BACKGROUND: There has been created an online communication tool with the
      objective to improve the communication among different levels of care, between
      Primary Care clinicians and Specialists. This tool is web 2.0 based technology
      (ECOPIH project). It allows to review clinical cases and to share knowledge. Our
      study will evaluate its impact in terms of reduction on the number of referrals
      to three specialties two years after the use of this tool. METHODS/DESIGN: Open,
      multicenter, controlled, non random intervention study over 24 months. Study
      population includes 131 Primary Care Physicians assigned to nine health centers.
      The study will compare the clinicians that use the ECOPIH with the ones that do
      not use the tool. Also, professionals that start to use the tool during the
      period time of the study will be included.The number of annual referrals during
      the first and second year will be analyzed and retrospectively compared with the
      previous year to the implementation of the tool. Moreover, it will be assessed
      the level of satisfaction of the professionals with the tool and to what extend
      the tool responds to their needs. DISCUSSION: The implementation of ECOPIH in the
      field of Primary Health Care can decrease the number of referrals from primary
      care to specialist care.It is expected that the reduction will be more noticeable
      in the group of professionals that use more intensively the tool. Furthermore, we
      believe that it can be also observed with the professionals that read the
      contributions of the others.We anticipate high degree of customer satisfaction as
      it is a very helpful resource never used before in our environment.

PMID- 24088388
TI  - Life-cycle energy use and greenhouse gas emissions of production of bioethanol
      from sorghum in the United States.
AB  - BACKGROUND: The availability of feedstock options is a key to meeting the
      volumetric requirement of 136.3 billion liters of renewable fuels per year
      beginning in 2022, as required in the US 2007 Energy Independence and Security
      Act. Life-cycle greenhouse gas (GHG) emissions of sorghum-based ethanol need to
      be assessed for sorghum to play a role in meeting that requirement. RESULTS:
      Multiple sorghum-based ethanol production pathways show diverse well-to-wheels
      (WTW) energy use and GHG emissions due to differences in energy use and
      fertilizer use intensity associated with sorghum growth and differences in the
      ethanol conversion processes. All sorghum-based ethanol pathways can achieve
      significant fossil energy savings. Relative to GHG emissions from conventional
      gasoline, grain sorghum-based ethanol can reduce WTW GHG emissions by 35% or 23%,
      respectively, when wet or dried distillers grains with solubles (DGS) is the co
      product and fossil natural gas (FNG) is consumed as the process fuel. The
      reduction increased to 56% or 55%, respectively, for wet or dried DGS co
      production when renewable natural gas (RNG) from anaerobic digestion of animal
      waste is used as the process fuel. These results do not include land-use change
      (LUC) GHG emissions, which we take as negligible. If LUC GHG emissions for grain
      sorghum ethanol as estimated by the US Environmental Protection Agency (EPA) are
      included (26 g CO2e/MJ), these reductions when wet DGS is co-produced decrease to
      7% or 29% when FNG or RNG is used as the process fuel. Sweet sorghum-based
      ethanol can reduce GHG emissions by 71% or 72% without or with use of co-produced
      vinasse as farm fertilizer, respectively, in ethanol plants using only sugar
      juice to produce ethanol. If both sugar and cellulosic bagasse were used in the
      future for ethanol production, an ethanol plant with a combined heat and power
      (CHP) system that supplies all process energy can achieve a GHG emission
      reduction of 70% or 72%, respectively, without or with vinasse fertigation.
      Forage sorghum-based ethanol can achieve a 49% WTW GHG emission reduction when
      ethanol plants meet process energy demands with CHP. In the case of forage
      sorghum and an integrated sweet sorghum pathway, the use of a portion of
      feedstock to fuel CHP systems significantly reduces fossil fuel consumption and
      GHG emissions. CONCLUSIONS: This study provides new insight into life-cycle
      energy use and GHG emissions of multiple sorghum-based ethanol production
      pathways in the US. Our results show that adding sorghum feedstocks to the
      existing options for ethanol production could help in meeting the requirements
      for volumes of renewable, advanced and cellulosic bioethanol production in the US
      required by the EPA's Renewable Fuel Standard program.

PMID- 24088389
TI  - Development and validation of the living with pulmonary hypertension
      questionnaire in pulmonary arterial hypertension patients.
AB  - BACKGROUND: The Living with Pulmonary Hypertension questionnaire (LPH) was
      adapted from the Minnesota Living with Heart Failure Questionnaire for use in
      patients with pulmonary arterial hypertension (PAH). Study objectives were to
      confirm the face and content validity, to assess the structure and psychometric
      properties, and provide guidance for the interpretation of the LPH. METHODS: A
      qualitative interview study was conducted with PAH patients in the US (n=12),
      Germany (n=14) and France (n=12) to evaluate the face and content validity of the
      LPH. Psychometric validation was performed using blinded data from a double
      blind, Phase III, clinical trial (n=196). Validation analyses were performed on
      baseline and week 12 (visit 6/last visit) data and included evaluation of: item
      response distributions, quality of completion, construct validity, reliability,
      clinical validity and responsiveness. Analyses to provide an estimation of the
      Minimal Important Difference (MID) for the LPH scores were performed. RESULTS:
      Cognitive debriefing interviews with 38 PAH patients indicated that the most
      commonly reported PAH symptoms and impacts are covered by LPH items. Patients
      found the LPH questionnaire relevant and comprehensive to their experience. Some
      suggestions were made to enhance the face validity of the LPH. The content
      validity of the questionnaire was supported. Results of the psychometric
      validation analyses (n=190) indicated that the LPH Emotional and Physical scores
      met the criteria for convergent and discriminant validity; for the total score
      all but two items met the test for item convergent validity. Internal consistency
      reliability was demonstrated by Cronbach's alpha values of >0.70 for all LPH
      scores. The LPH Physical and Total scores discriminated between World Health
      Organisation (WHO) Functional classes and 6 Minute walk test distances,
      indicating clinical validity and were also responsive to change in clinical
      severity, as measured by change in WHO functional class and Borg CR 10 Scale.
      Further investigation is required to confirm the responsiveness of the Emotional
      score. Estimation of MID using distribution-based methods indicated a change of 3
      points for the sub-scales and 7 for the total score to be clinically meaningful.
      CONCLUSION: The LPH is a valid and reliable instrument that meets FDA criteria.

PMID- 24088390
TI  - High SIRT1 expression is a negative prognosticator in pancreatic ductal
      adenocarcinoma.
AB  - BACKGROUND: Several lines of evidence indicate that Sirt1, a class III histone
      deacetylase (HDAC) is implicated in the initiation and progression of
      malignancies and thus gained attraction as druggable target. Since data on the
      role of Sirt1 in pancreatic ductal adenocarcinoma (PDAC) are sparse, we
      investigated the expression profile and prognostic significance of Sirt1 in vivo
      as well as cellular effects of Sirt1 inhibition in vitro. METHODS: Sirt1
      expression was analyzed by immunohistochemistry in a large cohort of PDACs and
      correlated with clinicopathological and survival data. Furthermore, we
      investigated the impact of overexpression and small molecule inhibition on Sirt1
      in pancreatic cancer cell culture models including combinatorial treatment with
      chemotherapy and EGFR-inhibition. Cellular events were measured quantitatively in
      real time and corroborated by conventional readouts including FACS analysis and
      MTT assays. RESULTS: We detected nuclear Sirt1 expression in 36 (27.9%) of 129
      PDACs. SIRT1 expression was significantly higher in poorly differentiated
      carcinomas. Strong SIRT1 expression was a significant predictor of poor survival
      both in univariate (p = 0.002) and multivariate (HR 1.65, p = 0.045) analysis.
      Accordingly, overexpression of Sirt1 led to increased cell viability, while small
      molecule inhibition led to a growth arrest in pancreatic cancer cells and
      impaired cell survival. This effect was even more pronounced in combinatorial
      regimens with gefitinib, but not in combination with gemcitabine. CONCLUSIONS:
      Sirt1 is an independent prognosticator in PDACs and plays an important role in
      pancreatic cancer cell growth, which can be levered out by small molecule
      inhibition. Our data warrant further studies on SIRT1 as a novel chemotherapeutic
      target in PDAC.

PMID- 24088391
TI  - Individual differences in the physiological effects of forest therapy based on
      Type A and Type B behavior patterns.
AB  - BACKGROUND: In recent years, the physiological relaxation effects of natural
      environments have been widely exploited, and although individual differences in
      the effects of forest therapy are known, assessment methods have not been clearly
      established. This study used a classification based on Type A and Type B behavior
      patterns to explain individual differences in physiological responses to forest
      environments. METHODS: We performed physiological experiments in 44 forest and
      urban (controls) areas. In total, 485 male university students (age, 21.8 +/- 1.6
      years) participated in the study. The subjects were asked to visit forest or
      urban environments randomly and observe each landscape for 15 min. The subjects'
      pulse rates and blood pressures were tested to evaluate their physiological
      responses. The Kwansei Gakuin daily life questionnaire was used to identify Type
      A and Type B behavior patterns in subjects. RESULTS: The pulse rate was
      significantly lower in the Type B group after exposure to forest areas than after
      exposure to urban areas, whereas no significant difference was observed in the
      Type A group. In addition, the pulse rate was significantly lower in the low
      scoring subjects in the Type B group, which was consistent with changes in their
      diastolic blood pressure. CONCLUSIONS: These results suggest that individual
      differences in pulse rate and blood pressure in response to forest environments
      can be explained by Type A and Type B behavior patterns.

PMID- 24088392
TI  - Effect of an educational intervention on HPV knowledge and vaccine attitudes
      among urban employed women and female undergraduate students in China: a cross
      sectional study.
AB  - BACKGROUND: Due to the potential of human papillomavirus (HPV) vaccination for
      decreasing cervical cancer rates in Mainland China, where some of the highest
      incidences in the world have been reported, our study aimed to assess HPV and HPV
      vaccine knowledge, and to evaluate the effect of a brief educational intervention
      on HPV knowledge and vaccine acceptability in Chinese undergraduate students and
      employed women. METHODS: This multi-center, cross-sectional study was conducted
      across five representative cities of the five main geographical regions of
      Mainland China. Participants were selected from one comprehensive university and
      three to four companies in each city for a total of six comprehensive
      universities and 16 companies. A 62-item questionnaire on HPV knowledge and HPV
      vaccine acceptability was administered to participants before and after an
      educational intervention. The intervention consisted of an informative group
      lecture. RESULTS: A total of 1146 employed women and 557 female undergraduate
      students were surveyed between August and November 2011. Baseline HPV knowledge
      was low among both groups--320/1146 (28%) of employed women and 66/557 (12%) of
      students had heard of HPV, while only 237/1146 (21%) of employed women and 40/557
      (7.2%) of students knew that HPV is related to cervical cancer. After educational
      instruction, 947/1061 (89%) of employed women and 193/325 (59%) of students knew
      the relationship between HPV and cervical cancer (chi2 = 1041.8, p < 0.001 and
      chi2 = 278.5, p < 0.001, respectively). Post-intervention, vaccine acceptability
      increased from 881/1146 (77%) to 953/1061 (90%), (p = <0.001) in employed women
      and 405/557 (73%) in students to 266/325 (82%), (p < 0.001). Women in both groups
      cited concerns about the HPV vaccine's safety, efficacy, and limited use to date
      as reasons for being unwilling to receive vaccination. 502/1146 (44%) of women
      were willing to vaccinate their children at baseline, which increased to 857/1061
      (81%) post-intervention, p < 0.001. CONCLUSIONS: Incorporation of our lecture
      based education initiative into a government-sponsored or school-based program
      may improve HPV-related knowledge and HPV vaccine acceptability. Further studies
      are needed to evaluate and standardize HPV education programs in China.

PMID- 24088393
TI  - Cooper pair transfer in nuclei.
AB  - The second-order distorted wave Born approximation implementation of two-particle
      transfer direct reactions which includes simultaneous and successive transfer,
      properly corrected by non-orthogonality effects, is tested with the help of
      controlled nuclear structure and reaction inputs against data spanning the whole
      mass table, and showed to constitute a quantitative probe of nuclear pairing
      correlations. 

PMID- 24088394
TI  - The shaping and functional consequences of the dosage effect landscape in
      multiple myeloma.
AB  - BACKGROUND: Multiple myeloma (MM) is a malignant proliferation of plasma B cells.
      Based on recurrent aneuploidy such as copy number alterations (CNAs), myeloma is
      divided into two subtypes with different CNA patterns and patient survival
      outcomes. How aneuploidy events arise, and whether they contribute to cancer cell
      evolution are actively studied. The large amount of transcriptomic changes
      resultant of CNAs (dosage effect) pose big challenges for identifying functional
      consequences of CNAs in myeloma in terms of specific driver genes and pathways.
      In this study, we hypothesize that gene-wise dosage effect varies as a result
      from complex regulatory networks that translate the impact of CNAs to gene
      expression, and studying this variation can provide insights into functional
      effects of CNAs. RESULTS: We propose gene-wise dosage effect score and genome
      wide karyotype plot as tools to measure and visualize concordant copy number and
      expression changes across cancer samples. We find that dosage effect in myeloma
      is widespread yet variable, and it is correlated with gene expression level and
      CNA frequencies in different chromosomes. Our analysis suggests that despite the
      enrichment of differentially expressed genes between hyperdiploid MM and non
      hyperdiploid MM in the trisomy chromosomes, the chromosomal proportion of dosage
      sensitive genes is higher in the non-trisomy chromosomes. Dosage-sensitive genes
      are enriched by genes with protein translation and localization functions, and
      dosage resistant genes are enriched by apoptosis genes. These results point to
      future studies on differential dosage sensitivity and resistance of pro- and anti
      proliferation pathways and their variation across patients as therapeutic targets
      and prognosis markers. CONCLUSIONS: Our findings support the hypothesis that
      recurrent CNAs in myeloma are selected by their functional consequences. The
      novel dosage effect score defined in this work will facilitate integration of
      copy number and expression data for identifying driver genes in cancer genomics
      studies. The accompanying R code is available at
      http://www.canevolve.org/dosageEffect/.

PMID- 24088395
TI  - Caring for women living with HIV: gaps in the evidence.
AB  - INTRODUCTION: In the management of HIV, women and men generally undergo the same
      treatment pathway, with gender differences being given limited consideration.
      This is in spite of accumulating evidence that there are a number of potential
      differences between women and men which may affect response to treatment,
      pharmacokinetics, toxicities and coping. There are also notable psychological,
      behavioural, social and structural factors that may have a unique impact on women
      living with HIV (WLWH). Despite our increasing knowledge of HIV and advances in
      treatment, there are significant gaps in the data relating specifically to women.
      One of the factors contributing to this situation is the under-representation of
      women in all aspects of HIV clinical research. Furthermore, there are clinical
      issues unique to women, including gynaecologic and breast diseases, menopause
      related factors, contraception and other topics related to women's and sexual
      health. METHODS: Using scoping review methodology, articles from the literature
      from 1980 to 2012 were identified using appropriate MeSH headings reflecting the
      clinical status of WLWH, particularly in the areas of clinical management, sexual
      health, emotional wellbeing and treatment access. Titles and abstracts were
      scanned to determine whether they were relevant to non-reproductive health in
      WLWH, and papers meeting inclusion criteria were reviewed. RESULTS: This review
      summarizes our current knowledge of the clinical status of WLWH, particularly in
      the areas of clinical management, sexual health, emotional wellbeing and
      treatment access. It suggests that there are a number of gender differences in
      disease and treatment outcomes, and distinct women-specific issues, such as
      menopause and co-morbidities, that pose significant challenges to the care of
      WLWH. CONCLUSIONS: Based on a review of this evidence, outstanding questions and
      areas where further studies are required to determine gender differences in the
      efficacy and safety of treatment and other clinical and psychological issues
      specifically affecting WLWH have been identified. Well-controlled and adequately
      powered clinical studies are essential to help provide answers to these questions
      and to contribute to activities aimed at improving the health and wellbeing of
      WLWH.

PMID- 24088397
TI  - Comparing cellular performance of Yarrowia lipolytica during growth on glucose
      and glycerol in submerged cultivations.
AB  - Yarrowia lipolytica is an attractive host for sustainable bioprocesses due to its
      ability to utilize a variety of carbon substrates and convert them to a range of
      different product types (including lipids, organic acids and polyols) under
      specific conditions. Despite an increasing number of applications for this yeast,
      relatively few studies have focused on uptake and metabolism of carbon sources,
      and the metabolic basis for carbon flow to the different products. The focus of
      this work was quantification of the cellular performance of Y. lipolytica during
      growth on glycerol, glucose or a mixture of the two. Carbon substrate uptake
      rate, growth rate, oxygen utilisation (requirement and uptake rate) and polyol
      yields were estimated in batch cultivations at 1 litre scale. When glucose was
      used as the sole carbon and energy source, the growth rate was 0.24 h-1 and
      biomass and CO2 were the only products. Growth on glycerol proceeded at
      approximately 0.30 h-1, and the substrate uptake rate was 0.02 mol L-1 h-1
      regardless of the starting glycerol concentration (10, 20 or 45 g L-1).
      Utilisation of glycerol was accompanied by higher oxygen uptake rates compared to
      glucose growth, indicating import of glycerol occurred initially via
      phosphorylation of glycerol into glycerol-3-phosphate. Based on these results it
      could be speculated that once oxygen limitation was reached, additional
      production of NADH created imbalance in the cofactor pools and the polyol
      formation observed could be a result of cofactor recycling to restore the balance
      in metabolism. 

PMID- 24088398
TI  - Dementia - an 'old' disorder with new perspectives.

PMID- 24088396
TI  - Spatial organization of dendritic cells within tumor draining lymph nodes impacts
      clinical outcome in breast cancer patients.
AB  - BACKGROUND: Dendritic cells (DCs) are important mediators of anti-tumor immune
      responses. We hypothesized that an in-depth analysis of dendritic cells and their
      spatial relationships to each other as well as to other immune cells within tumor
      draining lymph nodes (TDLNs) could provide a better understanding of immune
      function and dysregulation in cancer. METHODS: We analyzed immune cells within
      TDLNs from 59 breast cancer patients with at least 5 years of clinical follow-up
      using immunohistochemical staining with a novel quantitative image analysis
      system. We developed algorithms to analyze spatial distribution patterns of
      immune cells in cancer versus healthy intra-mammary lymph nodes (HLNs) to derive
      information about possible mechanisms underlying immune-dysregulation in breast
      cancer. We used the non-parametric Mann-Whitney test for inter-group comparisons,
      Wilcoxon Matched-Pairs Signed Ranks test for intra-group comparisons and log-rank
      (Mantel-Cox) test for Kaplan Maier analyses. RESULTS: Degree of clustering of DCs
      (in terms of spatial proximity of the cells to each other) was reduced in TDLNs
      compared to HLNs. While there were more numerous DC clusters in TDLNs compared to
      HLNs,DC clusters within TDLNs tended to have fewer member DCs and also consisted
      of fewer cells displaying the DC maturity marker CD83. The average number of T
      cells within a standardized radius of a clustered DC was increased compared to
      that of an unclustered DC, suggesting that DC clustering was associated with T
      cell interaction. Furthermore, the number of T cells within the radius of a
      clustered DC was reduced in tumor-positive TDLNs compared to HLNs. Importantly,
      clinical outcome analysis revealed that DC clustering in tumor-positive TDLNs
      correlated with the duration of disease-free survival in breast cancer patients.
      CONCLUSIONS: These findings are the first to describe the spatial organization of
      DCs within TDLNs and their association with survival outcome. In addition, we
      characterized specific changes in number, size, maturity, and T cell co
      localization of such clusters. Strategies to enhance DC function in-vivo,
      including maturation and clustering, may provide additional tools for developing
      more efficacious DC cancer vaccines.

PMID- 24088399
TI  - Adoption of two standard deviation notions of mental retardation for the
      diagnosis of dementia.

PMID- 24088400
TI  - Adaptation of the Montreal Cognitive Assessment for elderly Filipino patients.
AB  - OBJECTIVE: The Montreal Cognitive Assessment (MoCA) is an instrument that aids
      clinicians in detecting mild cognitive impairment and early Alzheimer's disease.
      The study aimed to adapt the MoCA for use in the Philippines, and determine its
      psychometric validity when used in the Filipino setting. METHODS: The MoCA was
      adapted by a multidisciplinary team working at the Memory Center of St. Luke's
      Medical Center, Manila, the Philippines. Contextual adaptation, rather than
      direct translation, was done. Pilot testing of the Filipino version of the MoCA
      (MoCA-P) was done on 12 grade 6 pupils and subsequently on 14 cognitively intact
      elderly people. Reliability testing of the MoCA-P was done on 25 elderly people
      by trained psychologists. Internal consistency, inter-rater and intra-rater
      reliability, as well as convergent and divergent validity of the MoCA-P were
      determined. RESULTS: The MoCA-P yielded a high level of internal consistency
      (Cronbach's alpha; = 0.938). Inter-rater and intra-rater reliability were 0.887
      (p <= 0.05) and 0.969 (p <= 0.05), respectively. The MoCA-P correlated negatively
      with the Epworth Sleepiness Scale (r = -0.233) and had a positive but low
      correlation with the Mini-Mental State Examination (r = 0.555). CONCLUSION:
      Contextual translation and pilot testing yielded several modifications of the
      MoCA. The MoCA-P is a reliable instrument for use in elderly Filipino patients.
      Further diagnostic validation of the MoCA-P to establish cutoff scores that would
      discriminate elderly individuals with normal cognition from those with dementia
      is needed to establish the clinical utility of the test.

PMID- 24088401
TI  - Differences in brain metabolism associated with agitation and depression in
      Alzheimer's disease.
AB  - OBJECTIVE: Agitation and depression are among the commonest behavioural and
      psychological symptoms exhibited by Alzheimer's disease patients. However, their
      pathophysiology remains unclear. We therefore investigated the relationship
      between the brain metabolism in the posterior cingulate gyrus and the
      dorsolateral prefrontal cortex, and agitation and depression in patients
      diagnosed with Alzheimer's disease. METHODS: We recruited 26 patients (14 women
      and 12 men) with a mean age of 75 years and probable Alzheimer's disease. All
      patients completed the Mini-Mental State Examination (MMSE), the Geriatric
      Depression Scale-Short Form (GDS) assessment, and the Cohen-Mansfield Agitation
      Inventory (CMAI) in order to evaluate cognition, depression, and agitation,
      respectively. All subjects underwent magnetic resonance imaging and (1)H-magnetic
      resonance spectroscopy of the brain. The ratios of N-acetylaspartate (NAA),
      choline (Cho), and myo-inositol (mI) to creatine (Cr) in the posterior cingulate
      gyrus and the dorsolateral prefrontal cortex were measured and compared with
      neuropsychological test results. RESULTS: The MMSE scores correlated positively
      with the NAA/Cr ratio in the left posterior cingulate gyrus (r = 0.56; p =
      0.001). The CMAI scores correlated negatively with the NAA/Cr ratio in the left
      posterior cingulate gyrus (r = -0.46; p = 0.02). The GDS scores correlated
      positively with the Cho/Cr ratio in the left dorsolateral prefrontal cortex (r =
      0.59; p = 0.01), and mI/Cr in both left (r = 0.47; p = 0.03) and right (r = 0.47;
      p = 0.03) cingulate gyri. CONCLUSIONS: Agitation and depression levels correlated
      with different neurochemical metabolites in specific brain areas. We conclude
      that various neuropsychiatric symptoms might have separate pathophysiologies.

PMID- 24088402
TI  - Initial evaluation of the training programme for health care professionals on the
      use of Malaysian clinical practice guidelines for management of dementia.
AB  - OBJECTIVE: The Malaysian Clinical Practice Guidelines (CPG) for Management of
      Dementia (second edition) was launched in April 2010 by the Ministry of Health
      Malaysia. A training programme for the management of dementia, involving all
      categories of staff working at primary and secondary centres, was implemented to
      ensure that care delivery for people with dementia was in accordance with the
      guidelines. The study aimed to look into improving knowledge and understanding of
      dementia following training, and to evaluate the effectiveness of the training
      programme using a clinical audit indicator recommended in the guidelines.
      METHODS: The study entailed 2 phases (at national and state levels). The first
      phase involved the CPG training programme run as a 1.5-day workshop, in which
      participants filled up pre- and post-workshop questionnaires. A second phase
      involved analysing all the referral letters to the memory clinic at the Hospital
      Sultan Ismail, Johor Bahru 1 year before and after the training programme.
      RESULTS: There was a significant improvement in knowledge about dementia and its
      management among the health care professionals following training. The mean
      percentage score for the pre-workshop test was 63% while for the post-workshop
      test it was 78%, giving a difference of 15%. Although there was an overall
      improvement in knowledge gain following training in both specialist and non
      specialist groups, these differences were not statistically significant (t =
      1.32; 95% confidence interval, -2.61 to 9.61; p = 0.25). The proportion of
      referrals with a possible diagnosis of dementia from primary clinic referrals to
      the memory clinic also increased from 18% to 44% after training. CONCLUSION:
      There was an overall improvement in the knowledge about dementia among the health
      care professionals following the training, which was reflected in the increase in
      referrals to the memory clinic. Although the initial results appeared to be
      promising, a multicentre study is warranted to conclude that the training had
      been effective.

PMID- 24088403
TI  - Spiritual activity is associated with better cognitive function in old age.
AB  - OBJECTIVE: This cross-sectional study aimed to explore the association between
      late-life spiritual activity participation and cognitive function in older
      Chinese adults in Hong Kong. METHODS: Participants aged 60 years or older without
      clinical dementia or major psychiatric disorders were recruited. Dementia
      severity and global cognitive function were assessed using the Clinical Dementia
      Rating and Cantonese version of the Mini-Mental State Examination, respectively.
      Cognitive performance was measured using 10-minute delayed recall, the Category
      Verbal Fluency Test, Visual Aural Digit Span Test, and Modified Card Sorting
      Test. Psychological status was assessed using the Chinese version of the Purpose
      in Life scale. Activities participated in were categorised into 6 domains of
      physical, cognitive, social, prosocial, spiritual, and recreational activities.
      RESULTS: A total of 380 participants were enrolled. Bivariate correlation showed
      that the composite score of cognitive function was positively correlated with
      aerobic exercise (r = 0.14; p = 0.01), cognitive activity (r = 0.30; p < 0.001),
      and spiritual activity (r = 0.16; p = 0.002). Multiple linear regression
      suggested that frequent participation in cognitive activity (B = 0.87, beta =
      0.22; 95% confidence interval [CI] = 0.52-1.25 and p < 0.001) and spiritual
      activity (B = 0.45, beta = 0.11; 95% CI = 0.13-0.76 and p = 0.01) were associated
      with better cognitive function after controlling for age and years of education.
      CONCLUSION: Engagement in spiritual activity may benefit cognitive function in
      old age. Longitudinal studies are recommended to further examine the causal
      relationship of spiritual activity and cognitive function.

PMID- 24088404
TI  - Study of lipids, insulin metabolism, and paraoxonase-2-311 polymorphism in
      patients with different subtypes of Alzheimer's disease (translated version).
AB  - OBJECTIVE: To investigate the characteristics of blood lipids, insulin
      metabolism, and paraoxonase-2-311 (PON2-311) polymorphism among patients with
      Alzheimer's disease with different types of dementia. METHODS: A total of 84
      patients with Alzheimer's disease, according to the National Institute of
      Neurological and Communicative Disorders and Stroke, and the Alzheimer's disease
      and Related Disorders Association clinical criteria for 'possible Alzheimer's
      disease', and with no family history of the condition, were enrolled. They were
      then categorised into 3 groups (senile dementia, presenile dementia, and mixed
      dementia) according to the diagnostic criteria of the Chinese Classification of
      Mental Disorders, third edition. Polymerase chain reaction-restriction fragment
      length polymorphism analysis was used to determine the presence of PON2-311
      polymorphism. Serum cholesterol, triglycerides, high-density lipoprotein, low
      density lipoprotein, and fasting blood sugar were measured. Fasting plasma
      insulin was measured using chemiluminescence. The basal-state method was used to
      assess insulin resistance expressed as insulin sensitivity index. The cognitive
      rating scale of the Mini-Mental State Examination, Activities of Daily Living
      scale, and Hachinski Ischemic Scale were used to establish the clinical features
      and severity of cognitive impairment. Differences in PON2-311C/S polymorphism,
      serum insulin, blood glucose, blood lipids, and neuropsychological score were
      analysed. RESULTS: The serum triglyceride and cholesterol levels of the presenile
      dementia group were significantly higher than those of the senile and mixed
      dementia groups (p < 0.01). The high-density lipoprotein level of the senile
      dementia group was significantly higher than that of the mixed dementia group (p
      < 0.05). The serum insulin level of the presenile dementia group was
      significantly higher than that of the senile (p < 0.05) and mixed dementia groups
      (p < 0.01). There were no significant differences in distribution of the PON2-311
      genotypes C/C, C/S, and S/S between the senile and mixed dementia groups, and no
      significant differences in C-allele and S-allele frequency between the 2 groups.
      CONCLUSIONS: The differences in serum triglycerides, cholesterol, high-density
      lipoprotein, and insulin levels between Alzheimer patients with senile,
      presenile, and mixed dementia found in this study suggest that patients with
      presenile dementia should monitor their lipid and insulin metabolism. No
      significant differences were found for PON2-311 genotypes or allele frequencies
      in patients with dementia due to Alzheimer's disease.

PMID- 24088405
TI  - The relationship between primary progressive aphasia and neurodegenerative
      dementia.
AB  - OBJECTIVE: To examine the relationship between primary progressive aphasia (PPA)
      and neurodegenerative dementia. METHODS: Subjects were selected from 1723
      consecutive patients who had undergone a medical examination at the Kumamoto
      University Hospital Dementia Clinic, Japan, from April 2007 to October 2012.
      First, patients with semantic dementia (SD) and patients with progressive non
      fluent aphasia were diagnosed by clinical diagnostic criteria for frontotemporal
      lobar degeneration. Next, in the same cohort, patients with PPA were diagnosed
      according to the recent international consensus criteria. The relationship and
      clinical symptoms including language and psychiatric symptoms in each patient
      group were then compared. RESULTS: In all, 12 of 27 SD patients fulfilled both SD
      and semantic variant PPA criteria (SD+PPA+ group), whereas the other 15 who met
      the SD criteria could not be included in the semantic variant PPA group due to
      prominent behavioural disturbances (SD+PPA- group). No significant differences in
      clinical characteristics and language functions were found between these 2
      groups. Neuropsychiatric symptoms were more severe in the SD+PPA- group.
      CONCLUSION: The results suggest the possibility that SD and semantic variant PPA
      may be identical, regardless of different severities of behavioural disturbance.
      When considering the language disorder of neurodegenerative dementia, it may be
      more important to diagnose the subtype of language disorder the patient has than
      to emphasise isolated language deficits.

PMID- 24088406
TI  - Clinical remission of late-onset depression in elderly Chinese: a short-term
      outcome study.
AB  - OBJECTIVE: Better understanding of the relationship between executive and memory
      functions and treatment response in late-onset depression may improve our ability
      to identify those individuals who are less likely to benefit from traditional
      pharmacological interventions. This study aimed to investigate the remission rate
      in elderly Chinese people with late-onset depression, and to examine the
      predictors of outcomes. METHODS: Patients aged 60 years or older with late-onset
      depression without dementia were recruited into the study. Mood symptoms were
      assessed by the 24-item Hamilton Rating Scale for Depression and Neuropsychiatric
      Inventory at 12 and 24 weeks. Cognitive domains assessed included global
      cognitive function, episodic memory, executive functions, and processing speed.
      The clinical characteristics and cognitive scores were compared among the early
      remitters, late remitters, and non-remitters. RESULTS: Of the 105 subjects, 42
      (40%) had remission at 12 weeks and were categorised as early remitters, 41 (39%)
      who did not remit at 12 weeks achieved remission at 24 weeks (late remitters),
      and 22 (21%) had not achieved remission at 24 weeks (non-remitters). Executive
      function, processing speed, episodic memory, apathy and depression severity were
      related to remission outcomes. Regression analyses found that severity of
      baseline apathy and depression were predictors of remission at 12 and 24 weeks,
      respectively. CONCLUSIONS: This study identified 2 subgroups of patients
      according to outcomes. One group with clinical characteristics similar to
      vascular depression achieved a late response to treatment. The other group were
      non-remitters who had features of depression-executive dysfunction syndrome,
      which might have underlying degenerative process and presented with the co
      occurrence of depression and mild cognitive impairment.

PMID- 24088407
TI  - Usefulness of metabolic syndrome score in the prediction of angiographic coronary
      artery disease severity according to the presence of diabetes mellitus: relation
      with inflammatory markers and adipokines.
AB  - BACKGROUND: It is a matter of debate whether metabolic syndrome (MS) improves
      cardiovascular risk prediction beyond the risk associated with its individual
      components. The present study examined the association of MS score with high
      sensitivity C-reactive protein (hs-CRP), interleukin-6 (IL-6), resistin,
      adiponectin, and angiographic coronary artery disease (CAD) severity according to
      the presence of DM. In addition, the predictive value of various clinical and
      biochemical parameters were analyzed, including the MS score for angiographic
      CAD. METHODS: The study enrolled 363 consecutive patients (196 men, 62 +/- 11
      years of age) who underwent coronary angiography for evaluation of chest pain.
      Blood samples were taken prior to elective coronary angiography. MS was defined
      by the National Cholesterol Education Program criteria, with MS score defined as
      the numbers of MS components. CAD was defined as > 50% luminal diameter stenosis
      of at least one major epicardial coronary artery. CAD severity was assessed using
      the Gensini score. RESULTS: Of the 363 patients studied, 174 (48%) had CAD and
      178 (49%) were diagnosed with MS. When the patients were divided into 4 subgroups
      according to MS score (0-1, 2, 3, 4-5), IL-6 levels and the CAD severity as
      assessed by the Gensini score increased as MS scores increased. In contrast,
      adiponectin levels decreased significantly as MS scores increased. When subjects
      were divided into two groups according to the presence of DM, the relationships
      between MS score and IL-6, adiponectin, and Gensini score were maintained only in
      patients without DM. Age, smoking, DM, MS score, and adiponectin independently
      predicted angiographic CAD in the whole population. However, age is the only
      predictor for angiographic CAD in patients with DM. CONCLUSIONS: In the presence
      of DM, neither adipokines nor MS score predicted angiographic CAD. However, in
      non-diabetic patients, IL-6 and adiponectin showed progressive changes according
      to MS score, and MS score was an independent predictor of CAD in patients without
      DM.

PMID- 24088408
TI  - Effects of storage temperature and semen extender on stored canine semen.
AB  - The objective of the present study was to determine an optimum temperature and
      extender for short-term transport of canine ejaculated semen. There was no
      significant difference in the qualities of semen diluted with two kinds of
      extender, egg yolk Tris-citrate fructose (EYT-FC) or glucose (EYT-GC) extender,
      between the 2, 8 or 12 and the 4 degrees C control groups during storage for up
      to 48 hr, while the 16-24 degrees C groups showed decreased sperm motility during
      storage for 48 hr. However, the 2 degrees C group showed slightly lower sperm
      motility and slightly higher sperm abnormality than the 4 degrees C group.
      Therefore, we concluded that semen qualities can be maintained for up to 48 hr
      when canine semen samples are extended with EYT-FC or EYT-GC and stored at a
      temperature in the range of 4-12 degrees C.

PMID- 24088409
TI  - Same Citius, Altius, Fortius...more women, crashes, and McTwists?
AB  - Almost half of the record 98 events being held at the 2014 Sochi Winter Olympic
      Games were either not held 20 years ago at Lillehammer or have been substantially
      modified. The Olympics as a global sports event are not stationary but must adapt
      and evolve in response to changing demands, just as the remarkable athletes who
      are competing do. While the Winter Olympics program has steadily grown since
      Chamonix in 1924, the rate of development has greatly accelerated in the last 20
      years. Three factors seem to be instrumental. First, the Winter Olympics program
      has become more gender balanced. Female hockey teams are battling for gold, and
      this year women will compete in ski jumping for the first time. Most Winter
      Olympics sports have equal numbers of events for men and women today, although
      female participation still lags somewhat behind. Second, many traditional events
      have been modified by sport-governing bodies toward a more "TV friendly" format.
      Time-trial starts have been replaced by mass or group starts. "Sprint" and team
      events have been added to spice up traditional sports like cross-country skiing
      and speed skating. Finally "extreme" sports like half-pipe and ski-cross have
      crossed over from the X Games to the Olympics, with some arguing that the
      Olympics need these popular sports more than the X Games sports need the
      Olympics. All of these changes create new research questions for sport scientists
      who are also willing to adapt and evolve. 

PMID- 24088410
TI  - The inhibitory effect of tongxieyaofang on rats with post infectious irritable
      bowel syndrome through regulating colonic par-2 receptor.
AB  - BACKGROUND: The aims of this study were to evaluate the effect and mechanism of a
      traditional Chinese medicine formula: Tongxieyaofang (TXYF) on Rats with Post
      Infectious Irritable Bowel Syndrome (PI-IBS). METHODS: SD male rats in adult were
      used to model PI-IBS and treated with TXYF at three dosage for 14 consecutive
      days, and then visceral sensation and the frequency of stool in PI-IBS rats were
      investigated. In addition, the contents of SP, TNF- alpha and IL-6 in colonic
      mucosal were analyzed by ELISA. Moreover faecal serine protease activity and PAR
      2 mRNA expression were measured by ultraviolet spectrophotometry and RT-PCR,
      respectively. RESULTS: Our study showed that TXYF attenuated visceral
      hyperalgesia and inhibited stool frequency in Campylobacter-stimulated Post
      Infectious Irritable Bowel Syndrome (PI-IBS) rats. Furthermore, TXYF decreased
      the colonic SP, TNF- alpha and IL-6 content in PI-IBS rats. In addition, the up
      regulated colonic mucosa PAR-2 mRNA expression in PI-IBS rats was significantly
      suppressed by orally TXYF. CONCLUSIONS: TXYF attenuated PI-IBS symptom by
      attenuating behavioral hyperalgesia and anti-diarrhea, the underlying mechanism
      was mediated by inhibiting PAR-2 receptor expression, reducing the levels of SP,
      TNF- alpha and IL-6 in colonic mucosa and decreasing faecal serine protease
      activity.

PMID- 24088411
TI  - Inhibitory effect of cervical trachea and chest wall vibrations on cough reflex
      sensitivity and perception of urge-to-cough in healthy male never-smokers.
AB  - BACKGROUND: Non-pharmacological options for symptomatic management of cough are
      desired. Although chest wall mechanical vibration is known to ameliorate cough
      reflex sensitivity, the effect of mechanical vibrations on perceptions of urge-to
      cough has not been studied. Therefore, we investigated the effect of mechanical
      vibration of cervical trachea, chest wall and femoral muscle on cough reflex
      sensitivity, perceptions of urge-to-cough as well as dyspnea. METHODS: Twenty
      four healthy male never-smokers were investigated for cough reflex sensitivity,
      perceptions of the urge-to-cough and dyspnea with or without mechanical
      vibration. Cough reflex sensitivity and urge-to-cough were evaluated by the
      inhalation of citric acid. The perception of dyspnea was evaluated by Borg scores
      during applications of external inspiratory resistive loads. Mechanical vibration
      was applied by placing a vibrating tuning fork on the skin surface of cervical
      trachea, chest wall and femoral muscle. RESULTS: Cervical trachea vibration
      significantly increased cough reflex threshold, as expressed by the lowest
      concentration of citric acid that elicited five or more coughs (C5), and urge-to
      cough threshold, as expressed by the lowest concentration of citric acid that
      elicited urge-to-cough (Cu), but did not significantly affect dypnea sensation
      during inspiratory resistive loading. On the other hand, the chest wall vibration
      not only significantly increased C5 and Cu but also significantly ameliorated the
      load-response curve of dyspnea sensation. CONCLUSIONS: Both cervical and trachea
      vibrations significantly inhibited cough reflex sensitivity and perception of
      urge-to-cough. These vibration techniques might be options for symptomatic cough
      management.

PMID- 24088412
TI  - Periosteum: biology and applications in craniofacial bone regeneration.
AB  - The bone-regenerative potentials of the periosteum have been explored as early as
      the 17th century. Over the past few years, however, much has been discovered in
      terms of the molecular and cellular mechanisms that control the periosteal
      contribution to bone regeneration. Lineage tracing analyses and knock-in
      transgenic mice have helped define the relative contributions of the periosteum
      and endosteum to bone regeneration. Additional studies have shed light on the
      critical roles that BMP, FGF, Hedgehog, Notch, PDGF, Wnt, and inflammation
      signaling have or may have in periosteal-mediated bone regeneration, fostering
      the path to novel approaches in bone-regenerative therapy. Thus, by examining the
      role that each pathway has in periosteal-mediated bone regeneration, in this
      review we analyze the status of the current research on the regenerative
      potential of the periosteum. The provided analysis aims to inform both clinician
      scientists who may have interest in the current studies about the biology of the
      periosteum as well as dental surgeons who may find this review useful to perform
      periosteal-harnessing bone-regenerative procedures.

PMID- 24088413
TI  - Treatment of hip dysplasia in patients with mucopolysaccharidosis type I after
      hematopoietic stem cell transplantation: results of an international consensus
      procedure.
AB  - BACKGROUND: Mucopolysaccharidosis type I (MPS-I) is a lysosomal storage disorder
      characterized by progressive multi-organ disease. The standard of care for
      patients with the severe phenotype (Hurler syndrome, MPS I-H) is early
      hematopoietic stem cell transplantation (HSCT). However, skeletal disease,
      including hip dysplasia, is almost invariably present in MPS I-H, and appears to
      be particularly unresponsive to HSCT. Hip dysplasia may lead to pain and loss of
      ambulation, at least in a subset of patients, if left untreated. However, there
      is a lack of evidence to guide the development of clinical guidelines for the
      follow-up and treatment of hip dysplasia in patients with MPS I-H. Therefore, an
      international Delphi consensus procedure was initiated to construct consensus
      based clinical practice guidelines in the absence of available evidence. METHODS:
      A literature review was conducted, and publications were graded according to
      their level of evidence. For the development of consensus guidelines, eight
      metabolic pediatricians and nine orthopedic surgeons with experience in the care
      of MPS I patients were invited to participate. Eleven case histories were
      assessed in two written rounds. For each case, the experts were asked if they
      would perform surgery, and they were asked to provide information on the aspects
      deemed essential or complicating in the decision-making process. In a subsequent
      face-to-face meeting, the results were presented and discussed. Draft consensus
      statements were discussed and adjusted until consensus was reached. RESULTS:
      Consensus was reached on seven statements. The panel concluded that early
      corrective surgery for MPS I-H patients with hip dysplasia should be considered.
      However, there was no full consensus as to whether such a procedure should be
      offered to all patients with hip dysplasia to prevent complications or whether a
      more conservative approach with surgical intervention only in those patients who
      develop clinically relevant symptoms due to the hip dysplasia is warranted.
      CONCLUSIONS: This international consensus procedure led to the construction of
      clinical practice guidelines for hip dysplasia in transplanted MPS I-H patients.
      Early corrective surgery should be considered, but further research is needed to
      establish its efficacy and role in the treatment of hip dysplasia as seen in MPS
      I.

PMID- 24088414
TI  - Maintaining genetic diversity using molecular coancestry: the effect of marker
      density and effective population size.
AB  - BACKGROUND: The most efficient method to maintain genetic diversity in
      populations under conservation programmes is to optimize, for each potential
      parent, the number of offspring left to the next generation by minimizing the
      global coancestry. Coancestry is usually calculated from genealogical data but
      molecular markers can be used to replace genealogical coancestry with molecular
      coancestry. Recent studies showed that optimizing contributions based on
      coancestry calculated from a large number of SNP markers can maintain higher
      levels of diversity than optimizing contributions based on genealogical data. In
      this study, we investigated how SNP density and effective population size impact
      the use of molecular coancestry to maintain diversity. RESULTS: At low SNP
      densities, the genetic diversity maintained using genealogical coancestry for
      optimization was higher than that maintained using molecular coancestry. The
      performance of molecular coancestry improved with increasing marker density, and,
      for the scenarios evaluated, it was as efficient as genealogical coancestry if
      SNP density reached at least 3 times the effective population size.However,
      increasing SNP density resulted in reduced returns in terms of maintained
      diversity. While a benefit of 12% was achieved when marker density increased from
      10 to 100 SNP/Morgan, the benefit was only 2% when it increased from 100 to 500
      SNP/Morgan. CONCLUSIONS: The marker density of most SNP chips already available
      for farm animals is sufficient for molecular coancestry to outperform
      genealogical coancestry in conservation programmes aimed at maintaining genetic
      diversity. For the purpose of effectively maintaining genetic diversity, a marker
      density of around 500 SNPs/Morgan can be considered as the most cost effective
      density when developing SNP chips for new species. Since the costs to develop SNP
      chips are decreasing, chips with 500 SNPs/Morgan should become available in a
      short-term horizon for non domestic species.

PMID- 24088415
TI  - Bioelectricity versus bioethanol from sugarcane bagasse: is it worth being
      flexible?
AB  - BACKGROUND: Sugarcane is the most efficient crop for production of (1G) ethanol.
      Additionally, sugarcane bagasse can be used to produce (2G) ethanol. However, the
      manufacture of 2G ethanol in large scale is not a consolidated process yet. Thus,
      a detailed economic analysis, based on consistent simulations of the process, is
      worthwhile. Moreover, both ethanol and electric energy markets have been
      extremely volatile in Brazil, which suggests that a flexible biorefinery, able to
      switch between 2G ethanol and electric energy production, could be an option to
      absorb fluctuations in relative prices. Simulations of three cases were run using
      the software EMSO: production of 1G ethanol + electric energy, of 1G + 2G ethanol
      and a flexible biorefinery. Bagasse for 2G ethanol was pretreated with a weak
      acid solution, followed by enzymatic hydrolysis, while 50% of sugarcane trash
      (mostly leaves) was used as surplus fuel. RESULTS: With maximum diversion of
      bagasse to 2G ethanol (74% of the total), an increase of 25.8% in ethanol
      production (reaching 115.2 L/tonne of sugarcane) was achieved. An increase of
      21.1% in the current ethanol price would be enough to make all three
      biorefineries economically viable (11.5% for the 1G + 2G dedicated biorefinery).
      For 2012 prices, the flexible biorefinery presented a lower Internal Rate of
      Return (IRR) than the 1G + 2G dedicated biorefinery. The impact of electric
      energy prices (auction and spot market) and of enzyme costs on the IRR was not as
      significant as it would be expected. CONCLUSIONS: For current market prices in
      Brazil, not even production of 1G bioethanol is economically feasible. However,
      the 1G + 2G dedicated biorefinery is closer to feasibility than the conventional
      1G + electric energy industrial plant. Besides, the IRR of the 1G + 2G
      biorefinery is more sensitive with respect to the price of ethanol, and an
      increase of 11.5% in this value would be enough to achieve feasibility. The
      ability of the flexible biorefinery to take advantage of seasonal fluctuations
      does not make up for its higher investment cost, in the present scenario.

PMID- 24088416
TI  - The effect of fermented red ginseng on depression is mediated by lipids.
AB  - OBJECTIVES: The cortico-limbic hypothalamic-pituitary-adrenal axis has emerged as
      an important area for the cause and treatment of depression. The primary aim of
      this study was to test the hypothesis that hormones, energy sources, and minerals
      have a causal relationship with depression. The secondary aim was to test whether
      consumption of fermented red ginseng (FRG) would influence that causal
      relationship. METHODS: For this study, 93 postmenopausal women were randomly
      divided into two groups. One group (49 women) was supplied with FRG capsules, and
      the other group (44 women) with placebo capsules, for 2 weeks. Both before and
      after the study, the participants filled out the Beck depression inventory
      questionnaire, and then blood samples were collected. The structural regression
      model was established. The causative latent variables were hormone
      (adrenocorticotropic hormone and cortisol), energy (low-density lipoprotein (LDL)
      cholesterol, total cholesterol, and blood glucose), mineral 1 (potassium, sodium,
      chloride, and iron), and mineral 2 (magnesium, calcium), and the resultant latent
      variables were cognitive depression (CD) and somatic depression. The goodness-of
      fit statistics of the final model were good (root mean square error of
      approximation =0.033, comparative fit index =0.877, and Tucker-Lewis index
      =0.870). RESULTS: The structural regression path of the energy factor on CD
      showed a significant difference between the FRG group (0.259) and the placebo
      group (-0.201). The factor loadings of total cholesterol (1.236) and LDL
      cholesterol (1.000) on the energy factor were much higher than that of glucose
      (0.166). CONCLUSION: Based on the analysis used in this model, the effect of FRG
      consumption on CD occurred via the energy factor, which is mainly attributable to
      cholesterol.

PMID- 24088417
TI  - Patient-experienced effect of an active implementation of a disease management
      programme for COPD - a randomised trial.
AB  - BACKGROUND: People living with chronic disease currently account for the majority
      of the total healthcare costs. The Central Denmark Region implemented a disease
      management programme (DMP) for chronic obstructive pulmonary disease (COPD) in
      2008. This presented an opportunity to examine the effect of an evidence-based,
      planned and proactive implementation of a DMP compared to the usual
      implementation strategy. METHODS: We performed a block- and cluster-randomised
      controlled trial with two groups and an extra external control group. The primary
      outcome was patients' assessment of their care after using an active
      implementation model for a DMP for COPD measured with the Patient-Assessment-of
      Chronic-Illness-Care (PACIC) instrument. At baseline, questionnaires were sent to
      2,895 patients identified by an algorithm based on health registry data on lung
      related contacts to the healthcare system. Patients were asked to confirm or
      refute their diagnosis of COPD. Of those who responded, 1,445 (72.8%) confirmed
      their diagnosis. PACIC data were collected at baseline and at a 12-month follow
      up for 744 (51.1%) patients. RESULTS: Comparing the three groups after the
      implementation of the DMP, we found a statistically significantly higher change
      in the PACIC score in the intervention group than in the control groups. No
      statistically significant differences were found between the control and the
      external control groups in any of the dimensions. CONCLUSIONS: Reinforcing the
      role of general practice as coordinator for care-and self-management-support with
      an active implementation of a DMP for COPD made patients score higher on the
      PACIC instrument, which indicates a better experience of the received healthcare.
      TRIAL REGISTRATION: NCT01228708.

PMID- 24088418
TI  - Moxibustion in the management of irritable bowel syndrome: systematic review and
      meta-analysis.
AB  - BACKGROUND: Irritable bowel syndrome (IBS) is a common functional
      gastrointestinal disorder. Many patients suffer from IBS that can be difficult to
      treat, thus complementary therapies which may be effective and have a lower
      likelihood of adverse effects are being sought.This systematic review and meta
      analysis aimed at critically evaluating the current evidence on moxibustion for
      improving global symptoms of IBS. METHODS: We searched Medline, EMBASE, the
      Cochrane Central Register of Controlled Trials, AMED, CINAHL, and CNKI databases
      for randomised controlled trials (RCTs) of moxibustion comparing with sham
      moxibustion, pharmacological medications, and other active treatments in patients
      with IBS. Trials should report global symptom improvement as an outcome measure.
      Risk of bias for each RCT was assessed according to criteria by the Cochrane
      Collaboration, and the dichotomous data were pooled according to the control
      intervention to obtain a risk ratio (RR) of global symptom improvement after
      moxibustion, with 95% confidence intervals (CI). RESULTS: A total of 20 RCTs were
      eligible for inclusion (n = 1625). The risk of bias was generally high. Compared
      with pharmacological medications, moxibustion significantly alleviated overall
      IBS symptoms but there was a moderate inconsistency among studies (7 RCTs, RR
      1.33, 95% CI [1.15, 1.55], I2 = 46%). Moxibustion combined with acupuncture was
      more effective than pharmacological therapy but a moderate inconsistency among
      studies was found (4 RCTs, RR 1.24, 95% CI [1.09, 1.41], I2 = 36%). When
      moxibustion was added to pharmacological medications or herbal medicine, no
      additive benefit of moxibustion was shown compared with pharmacological
      medications or herbal medicine alone. One small sham-controlled trial found no
      difference between moxibustion and sham control in symptom severity (mean
      difference 0.35, 95% CI [-0.77, 1.47]). Moxibustion appears to be associated with
      few adverse events but the evidence is limited due to poor reporting.
      CONCLUSIONS: This systematic review and meta-analysis suggests that moxibustion
      may provide benefit to IBS patients although the risk of bias in the included
      studies is relatively high. Future studies are necessary to confirm whether this
      finding is reproducible in carefully-designed and conducted trials and to firmly
      establish the place of moxibustion in current practice.

PMID- 24088419
TI  - Efficacy of 'Tailored Physical Activity' in reducing sickness absence among
      health care workers: design of a randomised controlled trial.
AB  - BACKGROUND: Health care workers have high physical work demands, involving
      patient handling and manual work tasks. A strategy for prevention of work-related
      musculoskeletal disorders can enhance the physical capacity of the health care
      worker. The aim of this study is to evaluate the efficacy of 'Tailored Physical
      Activity' for health care workers in the Sonderborg Municipality. METHODS/DESIGN:
      This protocol describes the design of a randomised controlled trial to assess the
      efficacy of 'Tailored Physical Activity' versus a reference group for health care
      workers in the Sonderborg Municipality. Inclusion criteria to be fulfilled:
      health care workers with daily work that includes manual work and with the
      experience of work-related musculoskeletal pain in the back or upper body.All
      participants will receive 'Health Guidance', a (90-minute) individualised
      dialogue focusing on improving life style, based on assessments of risk
      behaviour, on motivation for change and on personal resources. In addition, the
      experimental groups will receive 'Tailored Physical Activity' (three 50-minute
      sessions per week over 10 weeks). The reference group will receive only 'Health
      Guidance'.The primary outcome measure is the participants' self-reported sickness
      absence during the last three months due to musculoskeletal troubles, measured 3
      and 12 months after baseline.In addition, secondary outcomes include
      anthropometric measurements, functional capacity and self-reported number of sick
      days, musculoskeletal symptoms, self-reported health, work ability, work
      productivity, physical capacity, kinesiophobia and physical functional status.
      DISCUSSION: The results from this study will contribute to the knowledge about
      evidence-based interventions for prevention of sickness absence among health care
      workers. TRIAL REGISTRATION: ClinicalTrials.gov: NCT01543984.

PMID- 24088420
TI  - Cardiac tamponade complicating coronary perforation during angioplasty: short
      term outcomes and long-term survival.
AB  - BACKGROUND: Cardiac tamponade constitutes the most severe clinical consequence of
      a coronary perforation (CP) during percutaneous coronary intervention (PCI).
      METHODS: We analyzed 23,399 PCIs and identified 73 patients complicated by CP
      (0.31%), of which 26 developed tamponade (0.11%). Patients were divided into two
      groups: CP with tamponade (group A) and CP without tamponade (group B).
      Characteristics and outcomes were compared and a multivariate model was developed
      to evaluate the independent contribution of tamponade on mortality. RESULTS: All
      patients with tamponade were treated with pericardiocentesis. Tamponade increased
      the risk of death by more than 3-fold (odds ratio [OR] = 3.3; 95% confidence
      interval [CI],1.01-10.6; P=.047) relative to patients with CP but no tamponade.
      CP with tamponade during non-elective PCI carried a significantly worse long-term
      prognosis (P=.001) than the same complications during elective PCI. The use of
      glycoprotein IIb/IIIa inhibitors and bivalirudin did not differ between groups.
      Polytetrafluoroethylene-covered stents were used similarly between the two
      groups, while coil embolization was used more often in group A (P=.003). Emergent
      cardiac surgery was needed in 3 patients (11.5%) in group A versus 1 patient
      (2.1%) in group B. CONCLUSIONS: Tamponade complicating CP during PCI has short-
      and long-term major adverse effects. In-hospital mortality after tamponade and
      referral for emergent surgical treatment have decreased. Nonetheless, tamponade
      in this setting increases risk of death by >3-fold. PCI of complex lesions with
      an expected increased risk of perforation should be undertaken cautiously among
      patients with non-elective PCI because of increased early and late risk of death.

PMID- 24088421
TI  - Percutaneous device closure of ruptured sinus of valsalva aneurysm: a preliminary
      experience.
AB  - OBJECTIVE: To evaluate the immediate and mid-term outcomes of percutaneous device
      closure using patent ductus arteriosus (PDA) or ventricular septal defect (VSD)
      occluders in patients with ruptured sinus of Valsalva aneurysm (RSVA). METHODS:
      Ten patients (6 males and 4 females; age range, 19-63 years) were selected for
      the percutaneous device closure of RSVA between January 2005 and September 2011.
      In 2 patients, RSVA originated from the right coronary sinus (RCS) and ruptured
      into the right atrium (RA); in 6, from the RCS into the right ventricle,
      including 2 with very small VSDs; and in 2, from non-coronary sinus into the RA.
      RESULTS: The defects were angiographically found to be 7-15 mm at their narrowest
      end. All the defects were successfully occluded using either a PDA occluder 2-4
      mm larger than the narrowest end or a VSD occluder 3-5 mm larger than the
      narrowest end. No coronary arteries were checked for patency after closure.
      Immediately postoperative or follow-up echocardiography showed neither
      significant residual shunt nor severe aortic regurgitation (AR). Clinically, the
      patients developed no device embolism, infective endocarditis, or hemolysis. One
      patient was found to have newly-developed AR at the first follow-up at 1 month.
      The RSVA had been closed with a PDA occluder. One case suffered from
      periprocedural myocardial infarction without any symptoms. CONCLUSION: It is
      feasible and effective to use percutaneous device closure of RSVA with a PDA or
      VSD occluder.

PMID- 24088422
TI  - Transapical closure of mitral paravalvular leaks with use of amplatzer vascular
      plug III.
AB  - INTRODUCTION: Paravalvular leak (PVL) may complicate cardiac valve replacement
      surgery. Radical treatment is required if a PVL produces heart failure (HF)
      symptoms or severe hemolysis. Even though transcatheter PVL closure (TPVLC) has
      become a valid alternative to reoperation, a number of anatomical conditions may
      prove technically challenging for transvascular access. We intended to verify the
      utility of transapical access in such settings. METHODS: We report a prospective
      series of 7 patients with mitral PVLs who underwent transapical TPVLC. The Heart
      Team made the choice of treatment and Amplatzer Vascular Plug III devices were
      used off-label as occluders. RESULTS: Transapical TPVLC enabled excellent sealing
      of mitral PVL in 6 cases. This resulted in HF symptom reduction and decreased NT
      proBNP plasma concentration. No procedure-related complications occurred.
      CONCLUSIONS: Transapical access seems to be an efficient and safe alternative for
      transvascular approach for mitral TPVLC, but further technical development is
      still needed.

PMID- 24088423
TI  - Comparison of transvenous versus transthoracic catheter-based device closure of
      patent ductus arteriosus with amplatzer duct occluder.
AB  - OBJECTIVE: This study compared the clinical outcome of the transvenous versus
      transthoracic approach for closure of patent ductus arteriosus (PDA). BACKGROUND:
      There are no data regarding the results of transvenous versus transthoracic
      catheter-based device closure of PDA with Amplatzer duct occluder (ADO) despite
      their increasing use as alternatives to conventional surgery. METHODS: In this
      observational study, a total of 150 consecutive patients with PDA were allocated
      either to the transvenous approach (group A, n = 108) and the transthoracic
      approach (group B, n = 42) by using ADO between January 2010 and April 2012.
      Echocardiography was performed to evaluate the prespecified initial and 6-month
      success of PDA closure. The technical indices and procedure-related major acute
      and chronic complications were documented. RESULTS: There were similar initial
      success rates (98.2% vs 100%; P>.05) and 6-month success rates (99.1% vs 100%;
      P>.05) between groups, and group A had fewer major acute complications (3.7% vs
      85.7%; P<.001), shorter operating time (1.3 hours vs 2.1 hours; P<.001),
      Intensive Care Unit stay (0 hours vs 23.0 hours; P<.001), and recovery time (3.8
      days vs 9.5 days; P<.001), and lower rates of general anesthesia (36.1% vs 100%;
      P<.001), blood transfusion (0.9% vs 71.4%; P<.001), and extra use of antibiotics
      (27.8% vs 78.6%; P<.001), and lower total cost of hospitalization ($3815.78 vs
      $5730.21; P<.001). CONCLUSIONS: Despite similar efficacy for duct closure with
      ADO, transvenous approach was associated with fewer acute complications, more
      periprocedural comfort, and lower cost; thus, transthoracic approach should not
      be a reasonable choice for duct closure except for particular indications.

PMID- 24088424
TI  - Preclosure of femoral vein access site with the suture-mediated Proglide device
      during MitraClip implantation.
AB  - This study was designed to show the feasibility, safety, and efficacy of venous
      access-site closure with a single 6 Fr suture-mediated Proglide (Abbott Vascular)
      during MitraClip procedures. METHODS: Preclosure of the right femoral vein with
      Proglide used for access with the 24 Fr guiding catheter was performed. A total
      of 72 patients undergoing MitraClip were enrolled in this study (28 patients
      retrospectively and 44 patients prospectively), of whom 42 patients underwent a
      groin examination with ultrasound 2 days after the procedure. RESULTS: Only 1
      patient (1.4%) needed transfusion of packed cells because of bleeding and
      hematoma in the groin due to Proglide failure. None of the patients that were
      examined with ultrasound revealed an arteriovenous fistula or a spurious
      aneurysm, a local thrombosis, or a local stenosis related to the Proglide device.
      CONCLUSION: This study demonstrates that vascular closure with the suture
      mediated Proglide system is feasible, safe, and efficacious in large venous sites
      of 24 Fr as needed in patients undergoing MitraClip implantation despite the
      necessity of anticoagulation or platelet inhibition.

PMID- 24088425
TI  - Impact on clinical outcomes of predilatation using the kissing-balloon technique
      for crossover stenting in true coronary bifurcation lesions.
AB  - BACKGROUND: Provisional crossover stenting has the potential risk of side-branch
      (SB) compromise, which may result in periprocedural myocardial infarction.
      Predilatation is a useful technique to prevent SB compromise. OBJECTIVES: The aim
      of this study was to assess the safety and efficacy of predilatation using the
      kissing-balloon technique (preKBT) during provisional crossover stenting compared
      with sequential predilatation on clinical outcomes in true coronary bifurcation
      lesions. METHODS: We retrospectively evaluated 204 consecutive non-left main true
      bifurcation lesions (182 patients) in whom provisional crossover stenting was
      performed with preKBT (preKBT group, n = 144) or sequential predilatation
      (sequential group, n = 60) from March 2006 to February 2012. RESULTS: There were
      30 lesions (20.8%) in the preKBT group that developed SB ostial dissection
      compared with 8 lesions (13.3%) in the sequential group (P=.241). There was no SB
      flow impairment or SB access failure due to SB ostial dissection. SB compromise
      (Thrombolysis in Myocardial Infarction <3) immediately after crossover stenting
      occurred in 5 lesions (3.5%) in the preKBT group versus 7 lesions (11.7%) in the
      sequential group (P=.043). Major adverse cardiac events at 6-8 months of follow
      up were observed in 5 lesions (3.5%) in the preKBT group versus 8 lesions (13.3%)
      in the sequential group (P=.022). CONCLUSIONS: Regardless of more complex
      bifurcation lesions in the preKBT group, preKBT successfully prevented SB
      compromise due to crossover stenting without unfavorable complications and
      improved the mid-term clinical outcome compared with sequential PTCA in patients
      with non-left main, true coronary bifurcation lesions.

PMID- 24088426
TI  - Risk of cerebral embolism after interventional closure of symptomatic patent
      foramen ovale or atrial septal defect: a diffusion-weighted MRI and neuron
      specific enolase-based study.
AB  - OBJECTIVES: The aim of this single-center prospective study is to investigate the
      silent and clinically apparent cerebral embolic events after transcatheter
      closure of atrial septal defect (ASD) and patent foramen ovale (PFO). BACKGROUND:
      Although transcatheter closure of ASD and PFO is a widely accepted technique and
      has been proven to be safe and effective with different kinds of devices, there
      are few studies in the literature that report the peri-interventional cerebral
      embolism risk and neurological complications. In this study, we investigated the
      peri-interventional cerebral embolism incidence with diffusion-weighted magnetic
      resonance imaging (DW-MRI) and its relation to patients' clinical neurologic
      examination findings and plasma neuron-specific enolase (NSE) levels. METHODS:
      Sixteen patients with hemodynamically significant ASD and 14 symptomatic PFO
      patients underwent transcatheter closure procedures with new-generation PFO or
      ASD occluder devices. All cases were examined with DW-MRI before and after the
      transcatheter closure procedure. Patients were clinically examined for any signs
      of neurologic deficit at the time of MRI studies. Blood samples for NSE, a marker
      of brain tissue damage involved in an ischemic event, were taken before the
      procedure and at 12 and 24 hours after the procedure. RESULTS: Successful
      transcatheter closure of PFO or ASD was achieved in all patients. In the DW-MRI
      exam following the procedure, a new microembolic lesion was found in only 1 of 30
      patients (3.3%). None of the patients had positive clinical neurological exam
      findings. NSE levels after the procedure were found to be not correlated with
      presence of DWMRI lesion and intervention times. CONCLUSION: With the new
      generation ASD and PFO occluder devices, the incidence of clinically silent peri
      interventional cerebral embolic lesions after transcatheter closure of ASD and
      PFO is low. Plasma NSE levels offered no additional benefit for monitoring
      ischemic events after ASD and PFO transcatheter closure procedures.

PMID- 24088427
TI  - Transcatheter ventricular septal defect closure with a new nanoplatinum-coated
      nitinol device in a Swine model.
AB  - OBJECTIVES: To evaluate the feasibility and efficacy of a new nanoplatinum-coated
      nitinol device for transcatheter ventricular septal defect (VSD) closure in a
      swine model. BACKGROUND: In spite of its good closure results, the previous
      version of Amplatzer perimembranous VSD device had a relatively high incidence of
      complete heart block as compared to surgical closure. This new VSD device is made
      from meshed nitinol wires, nanoplatinum-coated and filled with polypropylene
      sheaths to enhance thrombogenicity. With special design, the device has minimal
      expanding pressure on the nearby tissue. This may reduce the possibility of
      atrioventricular block after implantation. METHODS: VSD was created in 12 pigs
      via retrograde aortic approach, by ventricular septal puncture with Brokenbrough
      needle and ventricular septal balloon dilation, under echocardiographic and
      fluoroscopic guidance. After imaging study, the device was deployed for VSD
      closure. RESULTS: The device was successfully deployed to close the created VSD
      in all 12 animals. Angiographic and echocardiographic studies demonstrated
      complete closure of the VSD in 11 animals. One animal had residual VSD leakage.
      Three animals had unstable hemodynamics and died within 12 hours after the
      procedure. The remaining 9 animals survived in normal condition. The autopsy
      findings demonstrated complete endothelialization at 8 weeks after implantation.
      CONCLUSION: Transcatheter VSD closure with the new nanoplatinum-coated nitinol
      device is feasible and efficacious. The good occlusion results and complete
      endothelialization after implantation in the swine model potentiates human
      application.

PMID- 24088428
TI  - Transradial access for peripheral and cerebrovascular interventions.
AB  - OBJECTIVES: In the present review, we report indications, equipment, techniques,
      results, and complications of transradial access (TRA) in peripheral as well as
      in cerebrovascular interventions. BACKGROUND: Percutaneous peripheral and
      cerebrovascular interventions are usually performed using transfemoral access;
      however, the risk of vascular complications with this approach is not negligible.
      Moreover, femoral access may be precluded by advanced vascular disease, and
      brachial access has been traditionally used as an alternative approach despite
      the risk of local complications. While TRA has gained wide acceptance for
      coronary procedures, little is known about its use for peripheral and
      cerebrovascular interventions. Thanks to dedicated equipment, most vascular
      territories may now also be treated by TRA. CONCLUSIONS: TRA may become the
      alternative access of choice for peripheral and cerebrovascular interventions
      when femoral access is precluded. In addition, TRA may become the preferred
      access for the treatment of selected peripheral lesions.

PMID- 24088429
TI  - Prospective comparison of palpation versus ultrasound-guided radial access for
      cardiac catheterization.
AB  - BACKGROUND: Radial access is increasingly used for both diagnostic and
      interventional cardiac procedures. Prospective data comparing ultrasound- versus
      palpation-guided radial catheterization are largely lacking. METHODS: In this
      prospective, single-center study, a total of 183 consecutive patients scheduled
      for transradial cardiac catheterization by an experienced interventionalist were
      assigned 1:1 to either palpation- or ultrasound-guided radial access. Demographic
      and procedure parameters were prospectively recorded. RESULTS: Baseline
      demographic and clinical parameters did not differ significantly between the
      ultrasound group (n = 92) and palpation group (n = 91). The initial radial
      catheterization success rate (87% vs 86.8%; P=.999) and time to access (47
      seconds [interquartile range (IQR), 20-90 seconds] versus 31 seconds [IQR, 20-75
      seconds]; P=.179) did not differ between the ultrasound and palpation groups,
      respectively. Pulse quality (absent, weak, strong) was independently associated
      with access failure in both groups (P<.001). Obesity was associated with access
      failure in the palpation group (P=.005), but not in the ultrasound group
      (P=.544). In 3/12 cases (25%) in the ultrasound group and 2/6 cases (33%) in the
      palpation group, the operator was able to establish radial access using the
      alternative method (P=.710). If palpation-guided radial access failed, an
      additional ultrasound-guided attempt before crossover to femoral access was
      associated with a shorter overall time to access (525 seconds [IQR, 462-567
      seconds] versus 744 seconds [IQR, 722-788 seconds]; P=.016). CONCLUSIONS:
      Ultrasound-guided radial access seems to provide no substantial additional
      benefit over palpation-guided access alone. Attempting the alternative guiding
      methods to establish radial access before crossover to femoral access seems to be
      a reasonable approach.

PMID- 24088430
TI  - Antiplatelet and antithrombotic treatment after transcatheter aortic valve
      implantation - comparison of regimes.
AB  - OBJECTIVES: We compared procedural and follow-up complications of TAVI patients
      based on the type of antithrombotic treatment used (single-antiplatelet [SAPT] vs
      dual-antiplatelet [DAPT] vs warfarin). BACKGROUND: Despite growing operator
      experience and device development, vascular complications following transcatheter
      aortic valve implantation (TAVI) remain problematic. Bleeding complications and
      stroke are two of the main disadvantages compared with surgical aortic valve
      replacement. Correct choice of antiplatelet or antithrombotic treatment is
      therefore crucial, but remains empirical. METHODS: We analyzed a cohort of 171
      patients with symptomatic severe aortic stenosis who underwent TAVI using the
      CoreValve (Medtronic, Inc) in our center between December 2007 and June 2012. We
      assessed both procedural, in-hospital, and follow-up outcomes for vascular
      complications, stroke, myocardial infarction, bleeding complications, and death.
      RESULTS: Patients were aged 81.6 +/- 6.4 years; 47% were male. Treatment regimes
      were DAPT (34%), SAPT (53%), or warfarin (13%). When analyzing the combined
      endpoint of all-cause death, acute coronary events, stroke, or bleeding, the
      outcome was significantly worse in the DAPT group (in-hospital P=.01, 30-day
      follow-up P=.02). This difference was driven mainly by bleeding complications,
      with a trend toward higher rates of major bleeding events in the DAPT group vs
      SAPT group (P=.07 for both in-hospital and 30-day bleeding). The occurrence of
      major adverse cardiac and cerebrovascular events was statistically similar in all
      groups. CONCLUSION: This relatively small series suggests that DAPT does not
      protect patients from stroke, but may expose them to higher bleeding risk.
      Further study of this area is warranted.

PMID- 24088431
TI  - Dynamic damping of the aortic pressure trace during hyperemia: the impact on
      fractional flow reserve measurement.
AB  - We report on two cases that illustrate an important caveat in the measurement of
      fractional flow reserve (FFR) in coronary arteries. To obtain accurate FFR
      measurements, two fundamental requirements must be fulfilled. One is to minimize
      microvascular resistance; the other is that there is no damping of the proximal
      aortic pressure trace. A problem with either of these requirements can be a
      source of serious error in the measurement of FFR. In each case we present here,
      despite a good aortic pressure trace at the start of the procedure, there is
      dynamic damping of the pressure trace during hyperemia, secondary to axial
      migration of the guiding catheter into the left main stem (LMS). In both cases, a
      normal aortic pressure trace (Pa) is present at baseline. After intracoronary
      adenosine injection, there was a fall in both mean Pa and distal coronary
      pressure (Pd) concomitant with damping of Pa, evidenced by loss of the dicrotic
      notch and ventricularization of the pressure trace. The resultant FFR value is
      underestimated. As hyperemia wears off, both pressure traces return to normal
      with good articulation of the dicrotic notch. When the procedure was repeated
      taking care to ensure that the guide did not move into the LMS during hyperemia,
      the Pa trace remained stable following intracoronary adenosine, while mean Pd
      decreased as before. In both cases, hemodynamically significant lesions were
      demonstrated that had been masked by the artifactual drop in Pa during the first
      attempt. 

PMID- 24088432
TI  - Subintimal distal anchor technique for "balloon-uncrossable" chronic total
      occlusions.
AB  - Percutaneous coronary intervention (PCI) of chronic total occlusion (CTO)
      presents unique challenges and potential complications. The two most common
      failure modes are inability to cross the lesion with a guidewire and failure to
      cross the CTO with a balloon after successful guidewire crossing ("balloon
      uncrossable" CTO). We present a creative solution to assist crossing of balloon
      uncrossable CTOs that entails use of a balloon placed over a wire that has been
      advanced though the subintimal space to "anchor" the guidewire that has crossed
      through the CTO true lumen enabling lesion crossing with a balloon. 

PMID- 24088434
TI  - Radi pressurewire rupture and embolization to the right common carotid artery
      after crossing a bjork-shiley mechanical aortic valve.
AB  - Direct measurement of the left ventricular pressure in patients with mechanical
      prosthetic aortic valve is an important technical challenge. In the past,
      transseptal puncture or direct left ventricular accesses were the only available
      methods. The use of a pressure wire through mechanical aortic prosthesis has been
      described to be feasible and safe. We report the first case report of pressure
      guidewire entrapment through a single tilting disk valve (Bjork-Shiley), which
      resulted in hemodynamic collapse, rupture, and embolization of the pressure wire
      tip to the right common carotid artery and its successful snaring. 

PMID- 24088433
TI  - Efficacy of lacrosse NSE using the "leopard-crawl" technique on severely
      calcified lesions.
AB  - Calcified lesions often encounter difficulties associated with stent delivery and
      underexpansion. Lesion preparation of calcified lesions prior to stent
      implantation is important to facilitate stent delivery and provide concentric
      stent expansion. The Lacrosse NSE, a balloon catheter with 3 nylon elements,
      provides an efficacious scoring effect when used for predilatation of calcified
      lesions. Although bench testing on a calcified model verified that Lacrosse NSE
      and other scoring catheters provide a greater scoring effect compared to
      conventional plain old balloon angioplasty, delivery to target lesion location
      using standard delivery techniques for severely calcified lesions is typically
      more problematic. One method for overcoming the obstacles faced by difficult
      delivery is use of the "leopard-crawl" technique. This technique uses a low
      inflation pressure to create a wedge into the calcification and then subsequently
      advances the catheter during balloon deflation to facilitate catheter delivery
      across the stenosis. This technique is well suited for the Lacrosse NSE due to
      the unique catheter design. We hereby report on the initial clinical use of the
      leopard-crawl technique for facilitating catheter delivery in cases of severely
      calcified lesions in which standard delivery was unsuccessful, while creating an
      efficacious scoring effect into the calcified lesion that reflects the results of
      bench testing. 

PMID- 24088435
TI  - Combined use of invatec mo.ma proximal protection device and Solitaire AB
      retrievable stent for tandem occlusions in a patient with acute ischemic stroke.
AB  - Recanalization of tandem vascular occlusions in the setting of an acute stroke is
      problematic. Here we report a successful treatment of an acute ischemic stroke
      with tandem cervical internal carotid artery and middle cerebral artery
      occlusions. A 56-year-old woman presented with acute left-sided hemiplegia.
      Diffusion magnetic resonance imaging showed an acute infarction in the right
      frontal and parietal lobes. We planned to perform rescue endovascular treatment
      after fibrinolytic therapy failed. Stent-assisted carotid angioplasty with
      proximal embolic protection device was followed by stent-based mechanical
      thrombectomy of the proximal middle cerebral artery occlusion. Her neurological
      condition improved after the procedure with National Institutes of Health Stroke
      Scale of 3 points. The combination of proximal embolic protection device and
      retrievable Solitaire stent could be a feasible and safe treatment strategy in
      acute ischemic stroke patients with extra- and intracranial tandem occlusions. 

PMID- 24088436
TI  - Double-v side-branch stenting followed by main trunk stenting in type-a3
      trifurcation coronary artery disease using a dual-catheter technique - the triple
      tine fork technique.
AB  - We report on a 55-year-old male patient who presented with acute non-ST elevation
      inferolateral myocardial infarction. He underwent conventional coronary
      angiography 3 days after admission that revealed normal right coronary artery,
      30% plaque in midleft anterior descending artery as well as total proximal left
      circumflex artery occlusion, which proved to be a type-A3 trifurcation lesion
      after predilatation. The trifurcation was approached with triple wiring and
      tackled with a novel 4-stent strategy that predicates at first the distal two
      side branches and the distal main branch (MB) stenting using dual 6 and 7 Fr
      guiding catheters that were introduced via a bifemoral approach, followed by main
      trunk (proximal main vessel) stenting with final trissing-balloon inflation.
      Angiography at the end of the procedure revealed a triple-tine fork-like shape.
      There was no postprocedural pain or CPK leakage. One year later, the patient was
      free from any cardiac complaints. 

PMID- 24088437
TI  - A case of contrast-induced pancreatitis following cardiac catheterization.
AB  - Coronary heart disease remains the leading cause of death of men and women in the
      United States. Angiography and percutaneous coronary interventions (PCI) are an
      integral part in management of acute coronary syndromes. Well-defined
      complications of coronary angiography include allergic and anaphylactic
      reactions, vascular access complications, stroke, and contrast-induced kidney
      injury. Radiographic contrast agents (RCAs) are known to cause acute kidney
      injury. RCAs are also postulated to induce pancreatitis in experimental animal
      models. We present a patient with acute pancreatitis immediately following
      coronary angiography. Recent studies have described that the use of RCA is
      associated with worse prognosis in patients with ongoing pancreatitis. The
      pathophysiology of RCA-induced pancreatitis is poorly understood. Although
      extremely rare, RCA-induced pancreatitis should be considered in the appropriate
      clinical setting. 

PMID- 24088438
TI  - Influence of developmental stage and genotype on liver mRNA levels among wild,
      domesticated, and hybrid rainbow trout (Oncorhynchus mykiss).
AB  - BACKGROUND: Release of domesticated strains of fish into nature may pose a threat
      to wild populations with respect to their evolved genetic structure and fitness.
      Understanding alterations that have occurred in both physiology and genetics as a
      consequence of domestication can assist in evaluating the risks posed by
      introgression of domesticated genomes into wild genetic backgrounds, however the
      molecular causes of these consequences are currently poorly defined. The present
      study has examined levels of mRNA in fast-growing pure domesticated (D), slow
      growing age-matched pure wild (Wa), slow-growing size-matched pure wild (Ws), and
      first generation hybrid cross (W/D) rainbow trout (Oncorhynchus mykiss) to
      investigate the influence of genotype (domesticated vs. wild, and their
      interactions in hybrids) and developmental stage (age- or size-matched animals)
      on genetic responses (i.e. dominant vs. recessive) and specific physiological
      pathways. RESULTS: Highly significant differences in mRNA levels were found
      between domesticated and wild-type rainbow trout genotypes (321 mRNAs), with many
      mRNAs in the wild-domesticated hybrid progeny showing intermediate levels.
      Differences were also found between age-matched and size-matched wild-type trout
      groups (64 mRNAs), with unique mRNA differences for each of the wild-type groups
      when compared to domesticated trout (Wa: 114 mRNAs, Ws: 88 mRNAs), illustrating
      an influence of fish developmental stage affecting findings when used as
      comparator groups to other genotypes. Analysis of differentially expressed mRNAs
      (found for both wild-type trout to domesticated comparisons) among the genotypes
      indicates that 34.8% are regulated consistent with an additive genetic model,
      whereas 39.1% and 26.1% show a recessive or dominant mode of regulation,
      respectively. These molecular data are largely consistent with phenotypic data
      (growth and behavioural assessments) assessed in domesticated and wild trout
      strains. CONCLUSIONS: The present molecular data are concordant with
      domestication having clearly altered rainbow trout genomes and consequent
      phenotype from that of native wild populations. Although mainly additive
      responses were noted in hybrid progeny, the prevalence of dominant and non
      additive responses reveals that introgression of domesticated and wild genotypes
      alters the type of genetic control of mRNA levels from that of wild-type, which
      may lead to disruption of gene regulation systems important for developing
      phenotypes for optimal fitness in nature. A clear influence of both fish age and
      size (developmental stage) on mRNA levels was also noted in this study, which
      highlights the importance of examining multiple control samples to provide a
      comprehensive understanding of changes observed between strains possessing
      differences in growth rate.

PMID- 24088439
TI  - Pulmonary metastasectomy: are observational studies sufficient evidence for
      effectiveness?

PMID- 24088440
TI  - Who should adopt robotic surgery, and when?

PMID- 24088441
TI  - Invited commentary.

PMID- 24088442
TI  - Invited commentary.

PMID- 24088443
TI  - Invited commentary.

PMID- 24088444
TI  - Invited commentary.

PMID- 24088445
TI  - Invited commentary.

PMID- 24088446
TI  - Invited commentary.

PMID- 24088447
TI  - Invited commentary.

PMID- 24088448
TI  - Invited commentary.

PMID- 24088449
TI  - Invited commentary.

PMID- 24088450
TI  - Invited commentary.

PMID- 24088451
TI  - Invited commentary.

PMID- 24088452
TI  - Invited commentary.

PMID- 24088453
TI  - Invited commentary.

PMID- 24088454
TI  - Invited commentary.

PMID- 24088455
TI  - Invited commentary.

PMID- 24088456
TI  - Video-guided tube thoracostomy with use of an electrical nonfiberoptic endoscope.
AB  - PURPOSE: Tube thoracostomy is a common and generally safe procedure. However,
      potential hazards can occur during placement of the chest tube. Inasmuch as
      unexpected injuries may arise from tube thoracostomy, we propose a novel video
      guided method. DESCRIPTION: We used an independent complementary metal oxide
      semiconductor image sensor with a processing chip to obtain a front view image of
      the chest cavity. The device is connected to an aluminum shaft with four small
      light-emitting diode crystals in the tip, and a detachable small monitor with a
      battery inside. The apparatus is small and can be used to direct vision-guided
      tools in tube thoracostomy. EVALUATION: We performed video-guided tube
      thoracostomy in 6 patients with pleural adhesions. All patients experienced good
      tolerance to the procedure and had no immediate adverse events. The
      thoracostomies were performed by a single surgeon with good acceptability, and
      each procedure was completed in less than 10 minutes. CONCLUSIONS: In some cases
      of pleural adhesion, the video-guided thoracostomy may be a safer alternative to
      non-image guided tube thoracostomy.

PMID- 24088457
TI  - Invited commentary.

PMID- 24088458
TI  - Spontaneous perforation of the esophagus in a patient with achalasia.
AB  - Esophageal perforation in achalasia is rare. The risk would mainly follow
      pneumatic dilatation, and spontaneous perforation has not been described. We
      report a case of spontaneous rupture of the midesophagus in a 56-year-old woman
      with treated achalasia in whom the perforation occurred during a meal and was not
      preceded by emesis. A gastrografin swallow confirmed extravasation of contrast
      medium from the esophagus, and endoscopy revealed significant esophageal food
      stasis, consistent with achalasia, with a large tear in the midesophagus and
      gross mediastinal contamination. She subsequently underwent a three-stage
      esophagectomy with an uneventful recovery. 

PMID- 24088459
TI  - Endovascular repair in penetrating aortoesophageal foreign body injury.
AB  - Foreign body ingestion in adults is not as common as in children. Sharp foreign
      body ingestion is even rarer; however, it may result in perforation,
      inflammation, or fistula formation at various gastrointestinal levels. In our
      case, the patient was unaware of the foreign body ingestion and presented with
      retrosternal chest pain, odynophagia, and occasional choking. Endoscopy and
      computed tomography thorax scan revealed a piece of chicken bone penetrating the
      aorta through the esophageal wall. No signs of mediastinitis were found. The
      foreign body was retrieved endoscopically with simultaneous endovascular stent
      repair of the aorta. Postoperative recovery was uneventful. There is an
      associated high morbidity and mortality in such cases, mandating long-term follow
      up. 

PMID- 24088460
TI  - Temporary clamping of branch pulmonary artery for pulmonary hemorrhage after
      endarterectomy.
AB  - A 49-year-old man underwent pulmonary thromboendarterectomy for chronic
      thromboembolic pulmonary hypertension. A massive pulmonary hemorrhage developed,
      which was identified to be from the right lower lobe, when weaning off
      cardiopulmonary bypass was attempted. He was managed by temporary overnight
      clamping of the right pulmonary artery, after the upper lobe branch. The next
      morning the clamp was removed, the bleeding had stopped completely, and his chest
      was closed. The patient was discharged on the 21st day. At 14 months' follow-up,
      he is in New York Heart Association functional class I. In suitable patients,
      temporary clamping of branch pulmonary artery can be a useful salvage measure, as
      in this patient. 

PMID- 24088461
TI  - Huge inflammatory myofibroblastic tumor of pleura with concomitant nuchal
      fibroma.
AB  - Inflammatory myofibroblastic tumor (IMT) is a rare benign neoplasm. It is a
      challenging disease because the symptoms and radiologic findings are diverse and
      nonspecific. Although pulmonary IMT is the most common form, pleural origin is an
      extremely rare clinical entity. Nuchal fibroma (NF) is another rare benign
      neoplasm. We report herein a case of pleural IMT with concomitant NF in a 15-year
      old girl. To the best of our knowledge, this is the first report suggesting an
      association between IMT and NF, and our case had the largest reported
      intrathoracic IMT. Moreover, we found a possible association between IMT and
      increased CA-125 levels. 

PMID- 24088462
TI  - Malignant glomus tumor of the esophagus with mediastinal lymph node metastases.
AB  - Extracutaneous malignant glomus tumors are unusual, and their occurrence in the
      esophagus has been recognized with extreme rarity. We describe a 47-year-old man
      who presented with progressive dysphagia and weight loss. Upper gastrointestinal
      endoscopy, a barium esophagram, and chest computed tomography revealed an
      unusually large, aggressive soft mass at the middle portion of the esophagus. A
      curative resection (R0 resection) was achieved by means of Ivor-Lewis
      esophagectomy and mediastinal lymph node dissection. The histopathologic
      examination and immunohistochemical studies demonstrated a malignant glomus tumor
      of the esophagus with mediastinal lymph node metastases. 

PMID- 24088463
TI  - Valve-sparing aortic root replacement with translocation of anomalous left
      coronary artery.
AB  - An anomalous left main coronary artery arising from the right coronary with a
      single coronary ostium is an exceptionally rare anatomic variant. Here, we report
      a patient with a left main coronary artery arising from the right coronary and
      also an aortic root aneurysm associated with mild aortic insufficiency. Valve
      sparing aortic root replacement and coronary translocation were performed with an
      excellent outcome in this case. 

PMID- 24088464
TI  - The effect of pulmonary root translocation on the left ventricular outflow tract.
AB  - We report the effect of pulmonary root translocation on the left ventricular
      outflow tract. A double switch operation with pulmonary root translocation was
      performed in a 6-year-old boy whose diagnosis was dextrocardia, congenitally
      corrected transposition of the great arteries, ventricular septal defect, and
      pulmonary stenosis. Postoperative magnetic resonance imaging showed more natural
      left ventricular outflow than preoperatively (19 mm vs 22 mm in length between
      the top of the interventricular septum and the aortic valve). This technique does
      not require coronary transfer and enables preservation of the aortic root
      structure. The long-term results, including left ventricular outflow tract
      morphology, should be evaluated. 

PMID- 24088465
TI  - Bridge use of endovascular repair and delayed open operation for infected
      aneurysm of aortic arch.
AB  - We present the first clinical report of the successful treatment of an infected
      thoracic aortic arch aneurysm with the use of endovascular repair as a bridge to
      second-stage open operation. A 70-year-old patient underwent urgent endovascular
      repair through the right femoral approach because of a diagnosis of sepsis and
      impending rupture of an infected thoracic aortic arch aneurysm. After 2 weeks of
      medical treatment, we successfully performed explantation of the stent graft,
      wide debridement of the surrounding tissue, and in-situ replacement using a
      rifampicin-bonded four-branched prosthetic graft with omental flap. 

PMID- 24088466
TI  - Magnetic resonance imaging diagnosis of left atrial abscess after ablation of
      atrial fibrillation.
AB  - We report a 52-year-old patient with a late presentation of a fistula that
      occurred after catheter ablation for atrial fibrillation. A secondary left atrial
      wall abscess was diagnosed by upper endoscopy and cardiac magnetic resonance
      imaging. Emergency operative repair was successful, with no adverse cardiac or
      gastrointestinal sequelae. 

PMID- 24088467
TI  - Aortic valve replacement for critical aortic stenosis after bilateral lung
      transplantation.
AB  - Four years after bilateral lung transplantation, a 62-year-old man with critical
      aortic stenosis required aortic valve replacement. This is the first report of
      aortic valve replacement after bilateral lung transplantation. Anesthetic and
      surgical management are described. 

PMID- 24088468
TI  - Giant left atrial appendage: a rare anomaly.
AB  - A giant left atrial appendage is a rare congenital anomaly that has been reported
      on only a few occasions. We report two symptomatic patients with atrial
      fibrillation combined with a cerebellar infarct in one and dyspnea in the other.
      Both patients were treated surgically with resection of the giant left atrial
      appendage and radiofrequency pulmonary vein isolation. Recognition of this
      uncommon pathology can lead to timely surgical intervention. 

PMID- 24088469
TI  - Nontraumatic ascending aortic disruption.
AB  - This report documents a case of completely spontaneous ascending aortic
      disruption. A 54-year-old African American male day laborer presented with severe
      retro-sternal chest and back pain and shortness of breath. He had no history of
      hypertension, smoking, or trauma and was taking no medications. The computed
      tomographic angiography scan performed to exclude pulmonary embolism instead
      demonstrated a hemorrhagic pericardial effusion and an ascending aortic
      pseudoaneurysm. He was taken emergently to the operating room for repair of his
      ascending aorta. The histopathology report was normal. 

PMID- 24088470
TI  - Successful detection and surgical treatment of cardiac hemangioma with right
      ventricular invasion.
AB  - Cardiac hemangiomas are extremely rare benign tumors. These tumors are usually
      asymptomatic but they can present symptoms such as palpitations, shortness of
      breath, and arrythmia. We report the case of a 73-year-old man who presented with
      an abnormal shadow on chest computed tomography during follow-up for lung
      metastatic tumor after resection of his rectal cancer. A cardiac tumor was
      detected, and surgical resection and right ventricular plasty were successfully
      performed with the patient under cardiopulmonary bypass. Histopathologic
      examination revealed a benign cardiac hemangioma, which was categorized as a
      hemangioma of the mixed cavernous and capillary type. 

PMID- 24088471
TI  - Pulmonary embolization as the primary clinical manifestation of giant renal
      angiomyolipoma.

PMID- 24088472
TI  - A case of needle embolism.

PMID- 24088473
TI  - Partial anomalous pulmonary venous return to azygos vein with absent segmental
      bronchus.

PMID- 24088474
TI  - Strongyloides-associated left ventricular thrombus.

PMID- 24088475
TI  - Bronchoscopic intrabullous autologous blood instillation: a novel approach for
      the treatment of giant bullae.
AB  - The current standard therapy for patients with giant bullae is surgical
      bullectomy; however, high operative risk and comorbidities preclude surgical
      procedures in many patients. Autologous blood instilled directly into bullae can
      induce an inflammatory reaction, leading to scarring, fibrosis, and ultimately
      volume loss. We have treated 5 patients with this minimally invasive approach as
      day-case procedures using moderate sedation. Three of the 5 patients had
      shrinkage of the bullae, leading to large and clinically meaningful improvements
      in lung function, exercise capacity, and quality of life 3 months after
      treatment. 

PMID- 24088476
TI  - Concomitant slide tracheoplasty and cardiac operation for congenital tracheal
      stenosis associated with VACTERL.
AB  - The association of congenital tracheal stenosis and tracheoesophageal (TE)
      fistula is rare. Here, we report 2 patients with tracheobronchial stenosis
      (complete cartilage ring) involving the lower trachea and right bronchus. Both
      patients had associated VACTERL (vertebral anomalies, anal atresia,
      cardiovascular anomalies, TE, renal, and limb defects) congenital cardiac defects
      and tracheal diverticula after repair of the TE fistula in type C esophageal
      atresia. The stenotic segment began at the orifice of the TE fistula, which
      became diverticula after the TE fistula was repaired. Concomitant repair of
      congenital cardiac defects and a slide tracheoplasty with elimination of the
      diverticula were performed successfully.

PMID- 24088477
TI  - Hybrid repair of thoracoabdominal aneurysm: a two-stage approach.
AB  - Despite higher standards of perioperative care and refinements in operative
      techniques, conventional open repair of thoracoabdominal aneurysms (TAAAs) is
      still associated with remarkable morbidity and mortality rates. Hybrid procedures
      as an option to traditional surgical procedures are still debated, especially in
      elderly patients with severe comorbidities. We report the experience of our
      institution using a hybrid technique in a subgroup of high-risk patients in an
      attempt to improve the results. 

PMID- 24088478
TI  - Aortoplasty for management of the dilated distal ascending aorta during proximal
      aortic reconstruction.
AB  - When aneurysms of the ascending aorta extend into the arch, the conventional
      approach is replacement with a Dacron graft, including a distal beveled hemiarch
      anastomosis with the patient under hypothermic circulatory arrest. For certain
      cases, we propose an alternative strategy combining replacement of the proximal
      and middle segments of the ascending aorta with external wrapping aortoplasty for
      the distal segment. This "turtleneck" aortoplasty achieves successful complete
      repair of the ascending aorta without the risks associated with circulatory
      arrest. 

PMID- 24088480
TI  - The eggs may be teaching the chickens.

PMID- 24088481
TI  - Surgical treatment of myasthenia gravis: evident benefits and insidious pitfalls
      of mini-invasive techniques.

PMID- 24088482
TI  - Malignant pleural effusion: one size does not fit all.

PMID- 24088483
TI  - Combined repair of pectus excavatum and cardiopulmonary bypass surgery. What is
      the best strategy?

PMID- 24088484
TI  - Reply: To PMID 22513274.

PMID- 24088485
TI  - Reply: To PMID 23312791.

PMID- 24088486
TI  - Does sex also influence antibiotic penetration into presternal subcutaneous
      tissue?

PMID- 24088487
TI  - Reply: To PMID 23462262.

PMID- 24088488
TI  - The reliable change index for assessment of cognitive dysfunction after coronary
      artery bypass graft surgery.

PMID- 24088489
TI  - Reply: To PMID 24088488.

PMID- 24088490
TI  - Are different mechanical circulatory support devices important factors maximizing
      patient survival after heart transplant?

PMID- 24088491
TI  - Reply: To PMID 22921240.

PMID- 24088492
TI  - Transcatheter aortic valve implantation and atrioventricular valve regurgitation.

PMID- 24088493
TI  - Reply: To PMID 23063197.

PMID- 24088494
TI  - Transapical endovascular stenting of penetrating atherosclerotic ulcer of
      ascending aorta.
AB  - A 71-year-old woman presented with acute chest pain and was admitted at our
      institution. Computed tomography revealed a penetrating atherosclerotic ulcer in
      the ascending aorta with extensive intramural hematoma. A transapical
      endovascular stenting was successfully performed. Computed tomography at a 6
      month follow-up visit revealed a type I endoleak, which was restented through the
      same approach. Despite initial satisfactory results, follow-up revealed a
      persistent endoleak, so that a high-risk open surgical repair was required.
      Surgical replacement of the ascending aorta was successfully performed without
      postoperative neurologic deficit. 

PMID- 24088495
TI  - Anomalous origin of the right main bronchus from the esophagus.

PMID- 24088496
TI  - Thoracic wall abscess as a late complication of extrapleural plombage.

PMID- 24088497
TI  - Thymic neuroendocrine carcinoma producing ectopic adrenocorticotropic hormone and
      Cushing's syndrome.
AB  - Neuroendocrine carcinoma of the thymus, previously termed thymic carcinoid, is a
      rare clinical entity. Rarer still are such cases presenting with
      endocrinopathies. We report a case of thymic neuroendocrine carcinoma presenting
      with ectopic adrenocorticotroic hormone production and resultant Cushing's
      syndrome. 

PMID- 24088498
TI  - Multimodality therapy for large cell neuroendocrine carcinoma of the thymus.
AB  - A case of large cell neuroendocrine carcinoma of the thymus successfully treated
      with chemoradiation, followed by extended resection under cardiopulmonary bypass,
      is reported. A 44-year-old man diagnosed with thymic large cell neuroendocrine
      carcinoma received induction chemoradiation therapy (3 cycles of
      cisplatin/etoposide and 45 Gy of hyperfractionated radiation) because of invasion
      to the aortic arch and pulmonary trunk. After radiographic partial response was
      noted, a radical resection under cardiopulmonary bypass was performed. Pathologic
      examination revealed no viable cells in the tumor. The patient is alive 3 years
      later, without recurrence. Aggressive multimodality therapy could be an option
      for thymic large cell neuroendocrine carcinoma. 

PMID- 24088499
TI  - Sarcomatous degeneration in fibrous dysplasia of the rib cage.
AB  - Malignant degeneration in fibrous dysplasia is a rare occurrence. Most cases are
      reported in polyostotic fibrous dysplasia with predisposition of the femur,
      tibia, maxilla, and mandible. The most commonly observed malignant tumors are
      osteosarcoma, fibrosarcoma, and chondrosarcoma. We describe a case of a low-grade
      osteosarcoma occurring in polyostotic fibrous dysplasia of the rib cage in a 50
      year-old man. 

PMID- 24088500
TI  - Immunoglobulin g4-related disease presenting as an obstructing tracheal mass:
      consideration of surgical indications.
AB  - Immunoglobulin G4 (IgG4)-related disease is increasingly recognized in many
      organs; however, none are described in detail is the trachea. In addition, the
      role of surgical intervention in the disease has yet to be fully defined. We
      describe a patient with IgG4-related airway disease presenting as a low tracheal
      mass, which was treated with tracheal resection and reconstruction. This novel
      presentation of the disease highlights the importance of including IgG4-related
      disease in the differential diagnosis of tracheal masses. Further, possible
      indications for surgical therapy are considered. As the full clinical spectrum of
      IgG4-related disease continues to evolve, so too must approaches to disease
      management. 

PMID- 24088501
TI  - Arteriobronchial fistula complicating right upper lobectomy.
AB  - Bronchial stump fistula (BSF) is a known complication after lobectomy, although
      its incidence after lobe resection for non-small cell lung cancer usually does
      not exceed 2%. We present the case of a patient in whom a late BSF developed that
      led to a fatal pulmonary hemorrhage 4 weeks after right upper lobectomy and 4
      hours after emergency readmission. Such a pulmonary hemorrhage could have been
      prevented by pulmonary artery embolization and intrapericardial pneumonectomy.
      The decision to perform pneumonectomy as a preventative procedure without overt
      clinical symptoms was a difficult decision to reach, particularly given the
      likelihood of being unnecessarily aggressive. 

PMID- 24088502
TI  - Cardiac tamponade due to coronary artery rupture after pulmonary resection.
AB  - We present a case of cardiac tamponade after lung resection. A 68-year-old man
      underwent single-staged bilateral lung resection (right wedge resection and left
      S8 segmentectomy) for metastatic lung tumors from rectal cancer and lost
      consciousness on postoperative day 4. Because an enhanced whole-body computed
      tomography scan showed pericardial effusion as the only abnormal finding, we
      performed rethoracotomy, which revealed that the cardiac tamponade was due to
      coronary artery rupture. We suggest that it would be more reasonable to approach
      the pericardial space by rethoracotomy rather than median sternotomy because
      exploration of the surgical site is the first essential step. 

PMID- 24088504
TI  - Use of hydroxyethyl starch in critically ill patients.

PMID- 24088503
TI  - HOXB7 mRNA is overexpressed in pancreatic ductal adenocarcinomas and its
      knockdown induces cell cycle arrest and apoptosis.
AB  - BACKGROUND: Human homeobox genes encode nuclear proteins that act as
      transcription factors involved in the control of differentiation and
      proliferation. Currently, the role of these genes in development and tumor
      progression has been extensively studied. Recently, increased expression of HOXB7
      homeobox gene (HOXB7) in pancreatic ductal adenocarcinomas (PDAC) was shown to
      correlate with an invasive phenotype, lymph node metastasis and worse survival
      outcomes, but no influence on cell proliferation or viability was detected. In
      the present study, the effects arising from the knockdown of HOXB7 in PDAC cell
      lines was investigated. METHODS: Real time quantitative PCR (qRT-PCR) (Taqman)
      was employed to assess HOXB7 mRNA expression in 29 PDAC, 6 metastatic tissues, 24
      peritumoral tissues and two PDAC cell lines. siRNA was used to knockdown HOXB7
      mRNA in the cell lines and its consequences on apoptosis rate and cell
      proliferation were measured by flow cytometry and MTT assay respectively.
      RESULTS: Overexpression of HOXB7 mRNA was observed in the tumoral tissues and in
      the cell lines MIA PaCa-2 and Capan-1. HOXB7 knockdown elicited (1) an increase
      in the expression of the pro-apoptotic proteins BAX and BAD in both cell lines;
      (2) a decrease in the expression of the anti-apoptotic protein BCL-2 and in
      cyclin D1 and an increase in the number of apoptotic cells in the MIA PaCa-2 cell
      line; (3) accumulation of cell in sub-G1 phase in both cell lines; (4) the
      modulation of several biological processes, especially in MIA PaCa-2, such as
      proteasomal ubiquitin-dependent catabolic process and cell cycle. CONCLUSION: The
      present study confirms the overexpression of HOXB7 mRNA expression in PDAC and
      demonstrates that decreasing its protein level by siRNA could significantly
      increase apoptosis and modulate several biological processes. HOXB7 might be a
      promising target for future therapies.

PMID- 24088505
TI  - A multidisciplinary approach to study a couple of monozygotic twins discordant
      for the chronic fatigue syndrome: a focus on potential salivary biomarkers.
AB  - BACKGROUND: Chronic Fatigue Syndrome (CFS) is a severe, systemic illness
      characterized by persistent, debilitating and medically unexplained fatigue. The
      etiology and pathophysiology of CFS remains obscure, and diagnosis is formulated
      through the patient's history and exclusion of other medical causes. Thereby, the
      availability of biomarkers for CFS could be useful for clinical research. In the
      present study, we used a proteomic approach to evaluate the global changes in the
      salivary profile in a couple of monozygotic twins who were discordant for CFS.
      The aim was to evaluate differences of salivary protein expression in the CFS
      patient in respect to his healthy twin. METHODS: Saliva samples were submitted to
      two-dimensional electrophoresis (2DE). The gels were stained with Sypro, and a
      comparison between CFS subject and the healthy one was performed by the software
      Progenesis Same Spot including the Analysis of variance (ANOVA test). The
      proteins spot found with a >=2-fold spot quantity change and p<0.05 were
      identified by Nano-liquid chromatography electrospray ionization tandem mass
      spectrometry. To validate the expression changes found with 2DE of 5 proteins (14
      3-3 protein zeta/delta, cyclophilin A, Cystatin-C, Protein S100-A7, and zinc
      alpha-2-glycoprotein), we used the western blot analysis. Moreover, proteins
      differentially expressed were functionally analyzed using the Ingenuity Pathways
      Analysis software with the aim to determine the predominant canonical pathways
      and the interaction network involved. RESULTS: The analysis of the protein
      profiles allowed us to find 13 proteins with a different expression in CFS in
      respect to control. Nine spots were up-regulated in CFS and 4 down-regulated.
      These proteins belong to different functional classes, such as inflammatory
      response, immune system and metabolism. In particular, as shown by the pathway
      analysis, the network built with our proteins highlights the involvement of
      inflammatory response in CFS pathogenesis. CONCLUSIONS: This study shows the
      presence of differentially expressed proteins in the saliva of the couple of
      monozygotic twins discordant for CFS, probably related to the disease.
      Consequently, we believe the proteomic approach could be useful both to define a
      panel of potential diagnostic biomarkers and to shed new light on the
      comprehension of the pathogenetic pathways of CFS.

PMID- 24088506
TI  - High frequency distribution of heterogeneous vancomycin resistant Enterococcous
      faecium (VREfm) in Iranian hospitals.
AB  - BACKGROUND: Enterococcus faecium is a multi-resistant nosocomial pathogen causing
      infection in debilitated patients. Vancomycin-resistant enterococcus faecium
      (VREfm) are a major concern and increased dramatically worldwide especially in
      hospitals environment. The current study focused on determining the high
      prevalence and distribution patterns of antibiotic resistance and also its
      genetic linkages among various VREfm strains isolated from indoor hospitalized
      patients in four major Iranian teaching hospitals of Tehran. METHODS: The
      clinical samples were obtained from hospitalized patients during September 2010
      to June 2011 from different teaching hospitals of Tehran. Antibiotics Resistance
      patterns, minimum inhibition concentration (MIC) value for vancomycin,
      ampicillin, gentamicin and presence of genetic linkage among the isolates were
      determined by pulsed-field gel electrophoresis (PFGE). RESULTS: Overall, total of
      92 (41.4%) isolates were identified as E. faecium, 45 (49%) were resistant to
      vancomycin with an MIC50 of >= 128 mg/L. The results showed that simultaneous
      resistance to teicoplanin, ampicillin, gentamicin, ciprofloxacine, tetracycline
      and erythromycin were observed the most frequent pattern. All the vancomycin
      resistant E. faecium isolates carried the vanA gene. intensive care units (ICUs)
      and Kidney transplantation, are most probably the wards with highest risk of
      infection by VRE. 17 pulsotypes were also detected by PFGE, most of the related
      pulsotypes belongs to the same hospitals. CONCLUSIONS: This study shows the high
      alarming prevalence of Enterococcus faecium infection and similar clones of VREfm
      strains in Iranian hospitals with threatening resistance phenotypes. VIRTUAL
      SLIDES: The virtual slides for this article can be found here:
      http://www.diagnosticpathology.diagnomx.eu/vs/1270863903102282.

PMID- 24088507
TI  - Chronic heart failure is associated with transforming growth factor beta
      dependent yield and functional decline in atrial explant-derived c-Kit+ cells.
AB  - BACKGROUND: Cardiac c-Kit+ cells isolated from cardiac explant-derived cells
      modestly improve cardiac functions after myocardial infarction; however, their
      full potential has not yet been realized. For instance, the majority of potential
      candidates for cell therapy suffer from chronic heart failure (CHF), and it is
      unclear how this disease affects the explant-derived progenitor cells. Therefore,
      the objective of this study was to determine the effect of CHF on the number and
      phenotype of cardiac explant c-Kit+ progenitors and elucidate mechanisms of their
      regulation. METHODS AND RESULTS: Myocardial infarction was created by left
      anterior descending coronary artery occlusion. Sham-operated animals were used as
      a control group. CHF-developed infarcted animals were selected on the basis of
      left ventricle end-diastolic pressure >= 20 mm Hg and scar size >= 30%. Here, we
      found that CHF atrial explants produced less c-Kit+ cells than sham explants. CHF
      derived c-Kit+ cells exhibited upregulated transforming growth factor-beta (TGF
      beta) signaling, increased level of epithelial to mesenchymal transition markers,
      and diminished expression of pluripotency markers compared with shams. We show
      that intervention with TGF-beta signaling by inhibiting TGF-beta receptor type I
      or Smad 2/3 using small-molecule inhibitors improved c-Kit+ cell yield,
      attenuated epithelial to mesenchymal transition markers, stimulated the
      pluripotency marker Nanog, and improved efficiency of c-Kit+ cell differentiation
      toward cardiomyocyte-like cells in vitro. CONCLUSIONS: Taken together, our
      findings suggest that TGF-beta inhibition positively modulates c-Kit+ cell
      phenotype and function in vitro, and this strategy may be considered in
      optimizing cardiac progenitor function and cell expansion protocols for clinical
      application.

PMID- 24088508
TI  - Twenty-two-year population trends in sodium and potassium consumption: the
      Minnesota Heart Survey.
AB  - BACKGROUND: Limiting dietary sodium consumption is a core lifestyle
      recommendation for the prevention of hypertension. There is increasing evidence
      that low potassium consumption also increases hypertension risk. We estimated sex
      specific 22-year trends in sodium and potassium consumption. METHODS AND RESULTS:
      We used data from the Minnesota Heart Survey, which performs surveillance of risk
      factors for cardiovascular disease in the Minneapolis-St. Paul metropolitan area.
      The Minnesota Heart Survey is a random population-based sample of free-living
      adults aged 25 to 74. Surveys were conducted in 1985-1987 (n = 2273), 1990-1992
      (n = 2487), 1995-1997 (n = 1842), 2000-2002 (n = 2759), and 2007-2009 (n = 1502).
      Dietary intake of sodium and potassium was estimated from one 24-hour dietary
      recall. Over 22 years, age-adjusted sodium and potassium intake among men
      remained relatively stable in 1985-1987 and 2007-2009 (Ptrend = 0.41 and 0.29,
      respectively); sodium ranged from 3820 mg/day (1995-1997) to 3968 mg/day (2007
      2009) and potassium from 3111 mg/day (2000-2002) to 3249 mg/day (1995-1997).
      Sodium and potassium intake increased among women, from 2531 mg/day in 1985-1987
      to 2854 mg/day in 2007-2009 (Ptrend = 0.001) for sodium and from 2285 to 2533
      mg/day (Ptrend < 0.0001) for potassium. We observed stable or increasing sodium
      and potassium intake within some strata of age, education, and body mass index.
      CONCLUSIONS: Despite long-standing public health recommendations to limit sodium
      intake to < 2300 mg/day, high sodium intake levels have persisted over the past
      22 years. Furthermore, although potassium consumption increased in some subgroups
      over the study period, mean consumption remained significantly lower than the
      recommended 4700 mg/day in all groups.

PMID- 24088509
TI  - A retrospective analysis on the diagnostic value of ultrasound-guided
      percutaneous biopsy for peritoneal lesions.
AB  - BACKGROUND: Routine examinations have a low specificity and a low positive rate
      for the diagnosis of peritoneal lesions. This study aimed to evaluate the
      diagnostic value and safety of ultrasound-guided percutaneous peritoneal lesion
      biopsies in patients with ascites and/or abdominal distension with unclear
      causes. METHODS: A retrospective analysis was performed in 153 consecutive
      patients with ascites and/or abdominal distension with unclear causes. All of the
      patients showed abnormalities of the peritoneum or greater omentum after
      ultrasonography, and underwent ultrasound-guided percutaneous biopsies using a
      Bard auto-biopsy gun with 18- or 16-gauge biopsy needles. RESULTS: The success
      rate of the procedures was 100% (153/153) and the satisfaction rate of the tissue
      specimens in the biopsy was 91.5% (140/153). A specific histopathological
      diagnosis was made in 142 out of 153 patients, with an overall diagnostic
      accuracy of 92.8%. Among the diagnosed patients, 62 were peritoneal metastatic
      adenocarcinoma, 49 were peritoneal tuberculosis, 11 were peritoneal malignant
      mesothelioma, 8 were chronic peritoneal infections, 7 were pseudomyxoma
      peritonei, and 5 were primary peritoneal lymphoma. Only 11 patients did not get a
      pathologic diagnosis due to the lack of sufficient tissue specimen. No serious
      complications occurred. CONCLUSIONS: Ultrasound-guided percutaneous biopsy could
      be a simple, safe and accurate diagnostic method in patients with ascites and/or
      abdominal distension with unclear causes.

PMID- 24088510
TI  - Measuring dopaminergic function in the 6-OHDA-lesioned rat: a comparison of PET
      and microdialysis.
AB  - BACKGROUND: [18 F]fluorodopa (FDOPA) positron emission tomography (PET) allows
      assessment of levodopa (LDOPA) metabolism and is widely used to study Parkinson's
      disease. We examined how [18 F]FDOPA PET-derived kinetic parameters relate the
      dopamine (DA) and DA metabolite content of extracellular fluid measured by
      microdialysis to aid in the interpretation of data from both techniques. METHODS:
      [18 F]FDOPA PET imaging and microdialysis measurements were performed in
      unilaterally 6-hydroxydopamine-lesioned rats (n = 8) and normal control rats (n =
      3). Microdialysis testing included baseline measurements and measurements
      following acute administration of LDOPA. PET imaging was also performed using
      [11C]dihydrotetrabenazine (DTBZ), which is a ligand for the vesicular monoamine
      transporter marker and allowed assessment of denervation severity. RESULTS: The
      different methods provided highly correlated data. Lesioned rats had reduced DA
      metabolite concentrations ipsilateral to the lesion (p < 0.05 compared to
      controls), with the concentration being correlated with FDOPA's effective
      distribution volume ratio (EDVR; r = 0.86, p < 0.01) and DTBZ's binding potential
      (BPND; r = 0.89, p < 0.01). The DA metabolite concentration in the contralateral
      striatum of severely (>80%) lesioned rats was lower (p < 0.05) than that of less
      severely lesioned rats (<80%) and was correlated with the ipsilateral PET
      measures (r = 0.89, p < 0.01 for BPND) but not with the contralateral PET
      measures. EDVR and BPND in the contralateral striatum were not different from
      controls and were not correlated with the denervation severity. CONCLUSIONS: The
      demonstrated strong correlations between the PET and microdialysis measures can
      aid in the interpretation of [18 F]FDOPA-derived kinetic parameters and help
      compare results from different studies. The contralateral striatum was affected
      by the lesioning and so cannot always serve as an unaffected control.

PMID- 24088511
TI  - Prospects of III-nitride optoelectronics grown on Si.
AB  - The use of III-nitride-based light-emitting diodes (LEDs) is now widespread in
      applications such as indicator lamps, display panels, backlighting for liquid
      crystal display TVs and computer screens, traffic lights, etc. To meet the huge
      market demand and lower the manufacturing cost, the LED industry is moving fast
      from 2 inch to 4 inch and recently to 6 inch wafer sizes. Although Al2O3
      (sapphire) and SiC remain the dominant substrate materials for the epitaxy of
      nitride LEDs, the use of large Si substrates attracts great interest because Si
      wafers are readily available in large diameters at low cost. In addition, such
      wafers are compatible with existing processing lines for 6 inch and larger wafers
      commonly used in the electronics industry. During the last decade, much exciting
      progress has been achieved in improving the performance of GaN-on-Si devices. In
      this contribution, the status and prospects of III-nitride optoelectronics grown
      on Si substrates are reviewed. The issues involved in the growth of GaN-based LED
      structures on Si and possible solutions are outlined, together with a brief
      introduction to some novel in situ and ex situ monitoring/characterization tools,
      which are especially useful for the growth of GaN-on-Si structures.

PMID- 24088512
TI  - Using biomarkers to predict progression from clinically isolated syndrome to
      multiple sclerosis.
AB  - BACKGROUND: Detection of brain lesions disseminated in space and time by magnetic
      resonance imaging remains a cornerstone for the diagnosis of clinically definite
      multiple sclerosis. We have sought to determine if gene expression biomarkers
      could contribute to the clinical diagnosis of multiple sclerosis. METHODS: We
      employed expression levels of 30 genes in blood from 199 subjects with multiple
      sclerosis, 203 subjects with other neurologic disorders, and 114 healthy control
      subjects to train ratioscore and support vector machine algorithms. Blood samples
      were obtained from 46 subjects coincident with clinically isolated syndrome who
      progressed to clinically definite multiple sclerosis determined by conventional
      methods. Gene expression levels from these subjects were inputted into ratioscore
      and support vector machine algorithms to determine if these methods also
      predicted that these subjects would develop multiple sclerosis. Standard
      calculations of sensitivity and specificity were employed to determine accuracy
      of these predictions. RESULTS: Our results demonstrate that ratioscore and
      support vector machine methods employing input gene transcript levels in blood
      can accurately identify subjects with clinically isolated syndrome that will
      progress to multiple sclerosis. CONCLUSIONS: We conclude these approaches may be
      useful to predict progression from clinically isolated syndrome to multiple
      sclerosis.

PMID- 24088513
TI  - Characterization of essential oil from Citrus aurantium L. flowers: antimicrobial
      and antioxidant activities.
AB  - Citrus aurantium L. essential oil is commonly used as a flavouring agent. In the
      present study, the essential oil of fresh Citrus aurantium L. (CaEO) flowers
      cultivated in North East of Tunisia (Nabeul) was analyzed by GC-FID and GC-MS. 33
      compounds were identified, representing 99% of the total oil. Limonene (27.5%)
      was the main component followed by E-nerolidol (17.5%), alpha-terpineol (14%),
      alpha-terpinyl acetate (11.7%) and E. E-farnesol (8%). The antimicrobial activity
      of the CaEO was evaluated against a panel of 13 bacteria and 8 fungal strains
      using agar diffusion and broth microdilution methods. Results have shown that the
      CaEO exhibited moderate to strong antimicrobial activity against the tested
      species. The investigation of the mode of action of the CaEO by the time-kill
      curve showed a drastic bactericidal effect after 5 min using a concentration of
      624 MUg/ml. The antioxidant activities of the CaEO were assayed by DPPH and beta
      carotene tests. Results showed that CaEO displayed an excellent DPPH scavenging
      ability with an IC50 of 1.8 MUg/ml and a strong Beta-carotene bleaching
      inhibition after 120 min of incubation with an IC50 of 15.3 MUg/ml. The results
      suggested that the CaEO possesses antimicrobial and antioxidant properties, and
      is therefore a potential source of active ingredients for food and pharmaceutical
      industry.

PMID- 24088514
TI  - Chlorella is an effective dietary source of lutein for human erythrocytes.
AB  - Chlorella contains a high amount of carotenoids, especially lutein, and has
      received attention as a possible dietary source for improving carotenoid levels
      in human blood. In the present study, we performed a 2-month single arm human
      study, and investigated the efficacy of Chlorella supplementation (9 g
      Chlorella/day; equivalent to 32 mg lutein/day) on lutein and other carotenoid
      concentrations in plasma as well as erythrocytes of 12 healthy subjects.
      Following Chlorella supplementation, lutein was the predominant carotenoid in
      erythrocytes, showing a 4-fold increase (from 14 to 54 pmol/mL packed cells).
      After the one month without Chlorella ingestion, erythrocyte lutein then
      decreased to a basal level (17 pmol/mL packed cells). Erythrocyte carotenoid
      (lutein, zeaxanthin, alpha-carotene, and beta-carotene) levels were proportional
      to plasma carotenoid levels. The results suggest the transfer of Chlorella
      carotenoids, especially lutein, from plasma lipoprotein particles to the
      erythrocyte membrane. Chlorella intake would be effective for improving and
      maintaining lutein concentrations in human erythrocytes. 

PMID- 24088515
TI  - Resolution behavior of cis- and trans-octadecenoic acid isomers by AOCS official
      method using SP-2560 column.
AB  - The gas chromatography-flame ionization detector equipped with a higher polarity
      column (i.e., SP-2560) has often been used for the quantification of trans-fatty
      acids in food. In particular, AOCS Ce 1h-05, the official method of the American
      Oil Chemists' Society (AOCS), is a highly effective method to separate the
      isomers of trans-fatty acids. In this study, the resolution behavior and the
      response factors of cis- and trans-octadecenoic acid methyl ester (C18:1-ME)
      isomers separated by the AOCS Ce 1h-05 method were investigated, and the contents
      of each cis- and trans-C18:1-ME isomer in partially hydrogenated vegetable oil
      (PHVO) and milk fat were quantified by using the calibration curves obtained for
      the respective isomers. The relative response factors for the trans- and cis
      C18:1-ME isomers against the internal standard heneicosanoic acid methyl ester
      (C21:0-ME) were 1.031 +/- 0.040 (mean +/- SD) and 0.990 +/- 0.032, respectively.
      The relative response factors of trans-isomers tend to be higher than those of
      cis-C18:1-ME isomers. The peaks of cis-4-C18:1-ME, cis-5-C18:1-ME, cis-6-C18:1
      ME, cis-7-C18:1-ME, cis-8-C18:1-ME, and cis-9-C18:1-ME isomers overlapped with
      those of trans-C18:1-ME isomers. Both PHVO and milk fat contained many types of
      cis- and trans-C18:1 isomers, and the total contents of the trans-C18:1 isomer in
      PHVO and milk fat were 28.01 g and 3.62 g per 100 g oil, respectively. When the
      trans-C18:1-ME isomer was separated from the cis-C18:1-ME by using a silver-ion
      cartridge column before the analyses, the total contents of the trans-C18:1
      isomer in PHVO and milk fat were 23.03 g and 2.78 g per 100 g oil, respectively.
      The difference in the trans-C18:1 isomer content between the two methods was
      ascribed to the partial overlapping of cis-isomer peaks with the peaks of trans
      C18:1-ME isomers, in the chromatogram. 

PMID- 24088516
TI  - Quantification of triacylglycerol molecular species in cocoa butter using high
      performance liquid chromatography equipped with nano quantity analyte detector.
AB  - Triacylglycerol (TAG) molecular species were quantified through high-performance
      liquid chromatography (HPLC) equipped with a nano quantity analyte detector
      (NQAD). TAG standard compounds, i.e., 1,3-dipalmitoyl-2-oleoylglycerol (beta
      POP), 1-palmitoyl-2-oleoyl-3-stearoyl-rac-glycerol (beta-POS), and 1,3-distearoyl
      2-oleoylglycerol (beta-SOS), and natural cocoa butter were used for analyses.
      NQAD gave the first order equation passing through the origin for all TAG
      standard compounds. TAG molecular species in cocoa butter were quantified using
      the calibration curves and the obtained values were almost the same as the
      reported ones of conventional cocoa butter. Furthermore, a recovery test was also
      carried out and the values were almost 100. Therefore, HPLC-NQAD can be
      successfully used for the quantification of TAG molecular species in natural fats
      and oils. 

PMID- 24088517
TI  - Molecular and crystal structure of spiculisporic acid and correlation with the
      surface activity.
AB  - The crystal of spiculisporic acid, [4S, 5S-(4,5-dicarboxy-4-pentadecanolide)], is
      orthorhombic, and the space group is P21 21 21 with Z = 4 at 23 degrees C. The
      cell dimensions are as follows, a = 43.82 (1) A, b = 7.540 (2) A, c = 5.579 (2)
      A, V = 1843 (1) A3. The molecules form intermolecular networks linked by hydrogen
      bonds around their polar carboxylic moieties. The hydrophobicity of the lactone
      ring (gamma-butanolide) was evaluated at ca. 4 methylene linkages of n-alkyl
      chain from both of the molecular alignmental data and the surface active
      properties of sodium spiculisporates. Then, it was made clear that sodium
      spiculisporates, anionic polyfunctional biosurfactants, exerted a distinctive
      characteristic of lower critical micelle concentration (cmc) and gamma(cmc)
      (surface tension at the cmc), simultaneously, through their properties. On the
      other hand, sodium salts of the lactone-cleaved derivative of spiculisporic acid
      (O-acid), showed large dispersing and calcium ion sequestration properties due to
      their plural polar heads.

PMID- 24088518
TI  - Formation and cleansing performance of bicontinuous microemulsions in water/poly
      (oxyethylene) alkyl ether/ester-type oil systems.
AB  - Phase behaviors in water/poly(oxyethylene) dodecyl ether (C12EO(n), n = 4, 6,
      8)/cetyl isooctanoate (CIO) systems were studied. In the C12EO6 and C12EO8
      systems, self-assembled structures with positive curvatures, such as O/W
      microemulsions, and micellar cubic and hexagonal phases, were observed. A wider
      region of a lamellar liquid-crystalline phase, which included a narrow
      microemulsion region joined by a miscibility gap, was observed in the C12EO4
      system. The structure of the microemulsion phase in the C12EO4 system was
      characterized by pulsed-field-gradient NMR (PFG-NMR) and small angle X-ray
      scattering (SAXS) techniques. PFG-NMR measurements indicated that the structure
      of the microemulsion was bicontinuous; both water and oil phases were continuous
      within the microemulsion. Pair-distance distribution function, p (r), and
      structure factors obtained by Generalized Indirect Fourier Transformation (GIFT)
      analysis of the SAXS data showed that the microemulsion domain sizes decreased
      with an increase in the oil content. The structure of the bicontinuous
      microemulsion was consistent with the results of a detergency test, in which the
      microemulsion samples were applied to lipstick dirt on an artificial skin plate.
      Detergency was observed to be better for the microemulsion at lower oil contents
      because of the larger oil domain size at these low concentrations.

PMID- 24088519
TI  - Miscibility behavior of sphingomyelin with phytosterol derivatives by a Langmuir
      monolayer approach.
AB  - The miscibility behavior of palmitoyl sphingomyelin (PSM) with phytosterol
      derivatives of beta-sitosterol (SITO), beta-sitosteryl glucoside (SG), and beta
      sitosteryl glucoside palmitate (SGP) was systematically investigated using
      Langmuir monolayers. The surface pressure (pi)-molecular area (A) and surface
      potential (DeltaV)-A isotherms for binary PSM/SITO, PSM/SG, and PSM/SGP systems
      on 0.02 M Tris buffer with 0.13 M NaCl (pH 7.4) were measured as a function of
      the molar fraction of PSM (X(PSM)). The surface potentials (DeltaV) of the pure
      components were analyzed using the three-layer model proposed by Demchak and Fort
      [J. Colloid Interface Sci. 46 (1974) 191-203]. The contributions of the
      hydrophilic D-glucose moiety, hydrophobic palmitoyl group, and sphingomyelin
      group to the vertical component of the dipole moment (MU(?)) were evaluated. The
      thermodynamic quantities, based on the pi-A isotherms, revealed that PSM
      interacts attractively with all three phytosterol derivatives in the following
      order: SITO > SGP > SG. In addition, the two-dimensional phase diagram
      constructed based on the phase transition pressure (pi(eq)), from a liquid
      expanded to liquid-condensed state, and collapse (pi(c)) pressure shows that the
      two-component systems are all miscible with each other. The manner of miscibility
      between PSM/SG and PSM/SGP systems is found to be opposite in the large X(PSM)
      region. The interaction between the same molecules (PSM-PSM or SG-SG) is stronger
      than that of the different molecules (PSM-SG) in the PSM/SG system, and vice
      versa in the PSM/SGP system. These results suggest that the incorporation of a D
      glucose and palmitoyl group to a SITO molecule dramatically changes the
      miscibility behavior with PSM. Observations using fluorescence microscopy imaging
      also provide insights into miscibility behavior in the monolayer state.

PMID- 24088520
TI  - Tocotrienol (unsaturated vitamin E) suppresses degranulation of mast cells and
      reduces allergic dermatitis in mice.
AB  - In this study, we examined whether tocotrienol (T3) reduces allergic dermatitis
      in mice and suppresses degranulation of mast cells. First, allergic dermatitis
      was examined in the atopic dermatitis model NC/Nga mouse. Allergic dermatitis was
      induced using picryl chloride in mice with and without administration of T3 (1
      mg/day/mouse). Increases in scratching behavior, dermal thickening, and the serum
      histamine level were greatly reduced in mice treated with T3, indicating that T3
      reduces allergic dermatitis in vivo. Next, the effect of T3 on degranulation of
      mast cells was examined, since these cells release bioactive substances such as
      histamine. T3 significantly suppressed degranulation of mast cells and
      significantly reduced histamine release. The effect of T3 on protein kinase C
      (PKC) activity was also measured, since suppression of this activity may be
      associated with the mechanism underlying the antidegranulation effect of T3. T3
      significantly suppressed PKC activity. Therefore, we conclude that T3 suppresses
      degranulation of mast cells and reduces allergic dermatitis in mice through
      reduction of PKC activity. 

PMID- 24088521
TI  - Expression and characterization of a class III alcohol dehydrogenase gene from
      Gluconobacter frateurii in the presence of methanol during glyceric acid
      production from glycerol.
AB  - Some acetic acid bacteria have been shown to produce large amounts of glyceric
      acid (GA) from glycerol, which is a by-product of biodiesel fuel (BDF)
      production. Previously, a Gluconobacter strain was found that produced decreased
      amounts of GA from glycerol in the presence of methanol, a major ingredient of
      raw glycerol derived from the BDF industry. Thus, a comparative transcriptome
      analysis of Gluconobacter frateurii NBRC103465 was performed to investigate
      changes in gene expression during GA production from glycerol in the presence of
      methanol. Cells grown with methanol showed upregulated expression of a class III
      alcohol dehydrogenase homolog (adhC(Gf)) and decreased GA production. adhC(Gf)
      was cloned and expressed heterologously in Escherichia coli, and the presence of
      an additional protein with an approximate molecular mass of 39 kDa in the cytosol
      of the recombinant E. coli cells was identified by SDS-PAGE. Activity
      measurements of the cytosol revealed that the translational product of adhC(Gf)
      exhibited formaldehyde dehydrogenase activity in the presence of nicotinamide
      adenine dinucleotide and glutathione. Gluconobacter frateurii cells grown in 1%
      methanol-containing glycerol were found to have fivefold higher formaldehyde
      dehydrogenase activity than cells grown without methanol, suggesting that
      adhC(Gf) in G. frateurii cells functions in the dissimilation of methanol-derived
      formaldehyde.

PMID- 24088522
TI  - Clerodane diterpenes isolated from Polyalthia longifolia induce apoptosis in
      human leukemia HL-60 cells.
AB  - Polyalthia is a versatile genus of shrubs and trees found in tropic and sub
      tropic regions. In this study, three clerodane diterpenes, kolavenic acid (1),
      polyalthialdoic acid (2), and 16alpha-hydroxy-cleroda-3,13(14)Z-dien-15,16-olide
      (3) isolated from Polyalthia longifolia leaves were evaluated for their apoptotic
      potential against human leukemia HL-60 cells. Compounds 2 and 3 inhibited cell
      proliferation with IC50 values of 21.8 and 13.7 MUM, respectively. Morphological
      changes and DNA fragmentation analysis indicated that these diterpenes induce
      apoptotic cell death in the HL-60 cells. Our results revealed the importance of
      P. longifolia as a chemopreventive medicinal plant.

PMID- 24088523
TI  - Bioglycerol-based sulphonic acid functionalized carbon: an efficient and
      recyclable, solid acid catalyst for the regioselective azidolysis of epoxides in
      aqueous acetonitrile.
AB  - A convinent and efficient method was developed for the synthesis of 1,2
      azidoalcohols by ring opening of terminal epoxides with sodium azide employing
      glycerol-based sulphonic acid functionalized carbon as heterogeneous catalyst in
      aqueous acetonitrile. The reaction is highly regioselective and affords the
      corresponding products in excellent yields (78-100%) under mild reaction
      conditions. The catalyst exhibited efficient reusability without loosing its
      activity even after 5 cycles of azidolysis of methyl 10,11-epoxy undecanoate
      under optimized conditions within 2 h. 

PMID- 24088524
TI  - Production of sophorolipids from non-edible jatropha oil by Stamerella bombicola
      NBRC 10243 and evaluation of their interfacial properties.
AB  - To facilitate the development of bio-based chemicals from renewable and
      inexpensive natural resources, we sought to produce biosurfactants using non
      edible jatropha oil. Twenty yeasts known to produce biosurfactants were tested in
      this study, and Stamerella bombicola NBRC 10243 was found to use jatropha oil
      efficiently to produce sophorolipids (SLs) as a mixture of lactone-form SL (L-SL)
      and acid-form SL (A-SL). Under culture conditions using rice bran as the source
      of organic nutrients, the yield of SLs reached 122.6 g/L in 5-L jar fermentors
      after 9 d in culture. HPLC analysis of the culture medium showed that the levels
      of phorbol esters (PEs), major toxic components of the oil, decreased markedly
      with an increase in culture time, suggesting that the yeast degrades PEs.
      Although the SLs obtained by solvent extraction of the culture medium contained a
      small amount of PEs, the sodium salt of A-SL (A-SL-Na) obtained by alkaline
      treatment (5N NaOH, 80 degrees C) showed no PE peaks upon HPLC analysis. A-SL-Na
      had excellent surface activity with low CMC (9.0*10-4 M) and gamma(CMC) (29.6
      mN/m), which are lower than that of sodium dodecyl sulfate (SDS). The
      solubilizing ability of A-SL-Na toward for octanoic acid ([octanoic acid]/[A-SL
      Na]) was found to be 2.0, which is half that of SDS. Our findings should help
      improve SL production from non-edible feedstock and broaden the use of promising
      bio-based surfactants.

PMID- 24088525
TI  - Public health system readiness to treat malaria in Odisha State of India.
AB  - BACKGROUND: Early diagnosis and prompt treatment is a cornerstone of malaria
      control. In India, artemisinin combination therapy (ACT) became the first-line
      treatment for falciparum malaria and rapid diagnostic test (RDTs) kits were
      recommended for use at the grass-root level in the new malaria treatment policy
      (2010). Odisha State contributes about one-fourth of the total Indian malaria
      burden and 40% of falciparum infection. The present study assessed the health
      system readiness to deploy RDTs and ACT for malaria control across the State.
      METHODS: Data collection was carried out from February to July 2012. Five of
      Odisha's 30 districts were selected through stratified random sampling, with
      stratification based on the phased roll-out of ACT and RDT. Two administrative
      'blocks' were selected randomly in each district and data collected through
      health facility, auxiliary nurse midwives (ANMs) and accredited social health
      activist (ASHAs) assessments. Key informant interviews were conducted with
      individuals involved in the implementation of the malaria control programme.
      RESULTS: Of the 220 ANMs interviewed, 51.4% had been trained in malaria case
      management, including the use of ACT and RDT. A high proportion of ANM (80%) and
      AHSA (77%) had the necessary level of knowledge to be able to use RDT for malaria
      diagnosis. The proportion of ASHAs trained on malaria case management was 88.9%
      (209/235). However, 71% of ANM and 55% of ASHAs usually referred falciparum
      positive patients to the health facility for treatment, the major reason for
      referral being the non-availability of drugs at the ANM and ASHA level.
      CONCLUSION: The relatively high level of knowledge about how to diagnose and
      treat malaria at the grass-root level was undermined by the poor availability of
      RDTs, ACT and primaquine tablets. This was associated with an unnecessarily high
      referral rate and potential delays in the treatment of this potentially life
      threatening infection. Improvements in the supply chain for RDTs and ACT could
      dramatically enhance the effectiveness of malaria control in Odisha.

PMID- 24088526
TI  - Heart fatty acid binding protein and Abeta-associated Alzheimer's
      neurodegeneration.
AB  - BACKGROUND: Epidemiological and molecular findings suggest a relationship between
      Alzheimer's disease (AD) and dyslipidemia, although the nature of this
      association is not well understood. RESULTS: Using linear mixed effects models,
      we investigated the relationship between CSF levels of heart fatty acid binding
      protein (HFABP), a lipid binding protein involved with fatty acid metabolism and
      lipid transport, amyloid-beta (Abeta), phospho-tau, and longitudinal MRI-based
      measures of brain atrophy among 295 non-demented and demented older individuals.
      Across all participants, we found a significant association of CSF HFABP with
      longitudinal atrophy of the entorhinal cortex and other AD-vulnerable
      neuroanatomic regions. However, we found that the relationship between CSF HABP
      and brain atrophy was significant only among those with low CSF Abeta1-42 and
      occurred irrespective of phospho-tau181p status. CONCLUSIONS: Our findings
      indicate that Abeta-associated volume loss occurs in the presence of elevated
      HFABP irrespective of phospho-tau. This implicates a potentially important role
      for fatty acid binding proteins in Alzheimer's disease neurodegeneration.

PMID- 24088527
TI  - Cardiopulmonary resuscitation with chest compressions during sustained
      inflations: a new technique of neonatal resuscitation that improves recovery and
      survival in a neonatal porcine model.
AB  - BACKGROUND: Guidelines on neonatal resuscitation recommend 90 chest compressions
      (CCs) and 30 manual inflations (3:1) per minute in newborns. The study aimed to
      determine whether CC s during sustained inflations (SIs) improves the recovery of
      asphyxiated newborn piglets in comparison with coordinated 3:1 resuscitation.
      METHODS AND RESULTS: Term newborn piglets (n=8/group) were anesthetized,
      intubated, instrumented, and exposed to 45-minute normocapnic hypoxia followed by
      asphyxia. Piglets were randomly assigned to receive either 3:1 resuscitation (3:1
      group) or CCs during SIs (SI group) when the heart rate decreased to 25% of
      baseline. Piglets randomly assigned to the SI group received SIs with a pressure
      of 30 cm H2O for 30 s. During the SI, CCs at a rate of 120/min were provided. SI
      was interrupted after 30 s for 1 s before a further 30-s SI was provided. CCs
      were continued throughout SIs. CCs and SI were continued until the return of
      spontaneous circulation. Continuous respiratory parameters, cardiac output, mean
      systemic and pulmonary artery pressures, and regional blood flows were measured.
      Mean (standard deviation) time for return of spontaneous circulation was
      significantly reduced in SI group versus 3:1 group (32 [11] s versus 205 [113] s,
      respectively). In the SI group, administration of oxygen and epinephrine was
      significantly lower, whereas minute ventilation and exhaled CO2 were
      significantly increased. The SI group had significantly higher mean systemic and
      pulmonary arterial pressures during resuscitation in comparison with the 3:1
      group (51 [10] versus 31 [5] mm Hg; 41[7] versus 31 [7] mm Hg, respectively; all
      P<0.05), with improved cardiac output and carotid blood flow. CONCLUSIONS:
      Combining CCs and SIs significantly improved the return of spontaneous
      circulation with better hemodynamic recovery in asphyxiated newborn piglets in
      comparison with standard coordinated 3:1 resuscitation.

PMID- 24088528
TI  - Improving neonatal cardiopulmonary resuscitation hemodynamics: are sustained
      inflations during compressions the answer?

PMID- 24088529
TI  - Mitral regurgitation in transcatheter aortic valve replacement: the complexity of
      multivalvular disease.

PMID- 24088530
TI  - Interplay between mitral regurgitation and transcatheter aortic valve replacement
      with the CoreValve Revalving System: a multicenter registry.
AB  - BACKGROUND: Little is known of the prognostic significance of mitral
      regurgitation (MR) on transcatheter aortic valve replacement (TAVR), the impact
      of TAVR on MR severity, and the variables associated with possible post-TAVR
      improvement in MR. We evaluated these issues in a multicenter registry of
      patients undergoing CoreValve Revalving System-TAVR. METHODS AND RESULTS: Among
      1007 consecutive patients, 670 (66.5%), 243 (24.1%), and 94 (9.3%) presented with
      no/mild, moderate, and severe MR, respectively. At 1 month after TAVR, patients
      with severe or moderate MR showed comparable mortality rates (odds ratio, 1.1;
      95% confidence interval [95% CI], 0.7-1.55; P=0.2), but both were significantly
      higher compared with patients with mild/no MR (odds ratio, 2.2; 95% CI, 1.78
      3.28; P<0.001; and odds ratio, 1.9; 95% CI, 1.1-3.3; P=0.02, respectively). One
      year mortality was also similar between patients with severe and those with
      moderate MR (hazard ratio, 1.4; 95% CI, 0.94-2.4; P=0.06) and still significantly
      higher compared with patients with mild/no MR (hazard ratio, 1.7; 95% CI, 1.2
      3.41; P<0.001; and hazard ratio, 1.4; 95% CI, 1.2-2.2; P=0.03, respectively).
      Severe pulmonary hypertension, atrial fibrillation, and MR more than mild, but
      not an improvement of >=1 grade in MR severity, were independent predictors of
      mortality at 1 year. At 1 year, an improved MR was observed in 47% and 35% of
      patients with severe and moderate MR, respectively. The rate of low implantation
      was consistent across groups with improved, unchanged, or worsened MR. A
      functional type of MR and the absence of severe pulmonary hypertension and atrial
      fibrillation independently predicted the improvement in MR severity. CONCLUSIONS:
      Baseline MR greater than mild is associated with higher mortality after CoreValve
      Revalving System-TAVR. A significant improvement in MR was more likely in
      patients with functional MR and without severe pulmonary hypertension or atrial
      fibrillation. The improvement in MR did not independently predict mortality.

PMID- 24088532
TI  - LVQ-SMOTE - Learning Vector Quantization based Synthetic Minority Over-sampling
      Technique for biomedical data.
AB  - BACKGROUND: Over-sampling methods based on Synthetic Minority Over-sampling
      Technique (SMOTE) have been proposed for classification problems of imbalanced
      biomedical data. However, the existing over-sampling methods achieve slightly
      better or sometimes worse result than the simplest SMOTE. In order to improve the
      effectiveness of SMOTE, this paper presents a novel over-sampling method using
      codebooks obtained by the learning vector quantization. In general, even when an
      existing SMOTE applied to a biomedical dataset, its empty feature space is still
      so huge that most classification algorithms would not perform well on estimating
      borderlines between classes. To tackle this problem, our over-sampling method
      generates synthetic samples which occupy more feature space than the other SMOTE
      algorithms. Briefly saying, our over-sampling method enables to generate useful
      synthetic samples by referring to actual samples taken from real-world datasets.
      RESULTS: Experiments on eight real-world imbalanced datasets demonstrate that our
      proposed over-sampling method performs better than the simplest SMOTE on four of
      five standard classification algorithms. Moreover, it is seen that the
      performance of our method increases if the latest SMOTE called MWMOTE is used in
      our algorithm. Experiments on datasets for beta-turn types prediction show some
      important patterns that have not been seen in previous analyses. CONCLUSIONS: The
      proposed over-sampling method generates useful synthetic samples for the
      classification of imbalanced biomedical data. Besides, the proposed over-sampling
      method is basically compatible with basic classification algorithms and the
      existing over-sampling methods.

PMID- 24088531
TI  - Heme oxygenase-1 activity is involved in the control of Toxoplasma gondii
      infection in the lung of BALB/c and C57BL/6 and in the small intestine of C57BL/6
      mice.
AB  - Heme oxygenase-1 (HO-1) is an enzyme that catabolizes free heme, which induces an
      intense inflammatory response. The expression of HO-1 is induced by different
      stimuli, triggering an anti-inflammatory response during biological stress. It
      was previously verified that HO-1 is able to induce indoleamine 2,3-dioxygenase
      (IDO), an enzyme that is induced by IFN-gamma in Toxoplasma gondii infection. To
      verify the role of HO-1 during in vivo T. gondii infection, BALB/c and C57BL/6
      mice were infected with the ME49 strain and treated with zinc protoporphyrin IX
      (ZnPPIX) or hemin, which inhibit or induce HO-1 activity, respectively. The
      results show that T. gondii infection induced high levels of HO-1 expression in
      the lung of BALB/c and C57BL6 mice. The animals treated with ZnPPIX presented
      higher parasitism in the lungs of both lineages of mice, whereas hemin treatment
      decreased the parasite replication in this organ and in the small intestine of
      infected C57BL/6 mice. Furthermore, C57BL/6 mice infected with T. gondii and
      treated with hemin showed higher levels of IDO expression in the lungs and small
      intestine than uninfected mice. In conclusion, our data suggest that HO-1
      activity is involved in the control of T. gondii in the lungs of both mouse
      lineages, whereas the hemin, a HO-1 inducer, seems to be involved in the control
      of parasitism in the small intestine of C57BL/6 mice. 

PMID- 24088533
TI  - Heterogeneous solution deposition of high-performance adhesive hybrid films.
AB  - Interfaces between organic and inorganic materials are of critical importance to
      the lifetime of devices found in microelectronic chips, organic electronics,
      photovoltaics, and high-performance laminates. Hybrid organic/inorganic materials
      synthesized through sol-gel processing are best suited to address these
      challenges because of the intimate mixing of both components. We demonstrate that
      deposition from heterogeneous sol-gel solutions leads to the unique nanolength
      scale control of the through-thickness film composition and therefore the
      independent optimization of both the bulk and interfacial film properties.
      Consequently, an outstanding 3-fold improvement in the adhesive/cohesive
      properties of these hybrid films can be obtained from otherwise identical
      precursors. 

PMID- 24088534
TI  - The combined effect of chemoprophylaxis with single dose rifampicin and
      immunoprophylaxis with BCG to prevent leprosy in contacts of newly diagnosed
      leprosy cases: a cluster randomized controlled trial (MALTALEP study).
AB  - BACKGROUND: Despite almost 30 years of effective chemotherapy with MDT, the
      global new case detection rate of leprosy has remained quite constant over the
      past years. New tools and methodologies are necessary to interrupt the
      transmission of M. leprae. Single-dose rifampicin (SDR) has been shown to prevent
      57% of incident cases of leprosy in the first two years, when given to contacts
      of newly diagnosed cases. Immunization of contacts with BCG has been less well
      documented, but appears to have a preventive effect lasting up to 9 years.
      However, one major disadvantage is the occurrence of excess cases within the
      first year after immunization. The objective of this study is to examine the
      effect of chemoprophylaxis with SDR and immunoprophylaxis with BCG on the
      clinical outcome as well as on host immune responses and gene expression profiles
      in contacts of newly diagnosed leprosy patients. We hypothesize that the effects
      of both interventions may be complementary, causing the combined preventive
      outcome to be significant and long-lasting. METHODS/DESIGN: Through a cluster
      randomized controlled trial we compare immunization with BCG alone with BCG plus
      SDR in contacts of new leprosy cases. Contact groups of around 15 persons will be
      established for each of the 1300 leprosy patients included in the trial,
      resulting in approximately 20,000 contacts in total. BCG will be administered to
      the intervention group followed by SDR, 2 months later. The control group will
      receive BCG only. In total 10,000 contacts will be included in both intervention
      arms over a 2-year period. Follow-up will take place one year as well as two
      years after intake. The primary outcome is the occurrence of clinical leprosy
      within two years. Simultaneously with vaccination and SDR, blood samples for in
      vitro analyses will be obtained from 300 contacts participating in the trial to
      determine the effect of these chemo- and immunoprophylactic interventions on
      immune and genetic host parameters. DISCUSSION: Combined chemoprophylaxis and
      immunoprophylaxis is potentially a very powerful and innovative tool aimed at
      contacts of leprosy patients that could reduce the transmission of M. leprae
      markedly. The trial intends to substantiate this potential preventive effect.
      Evaluation of immune and genetic biomarker profiles will allow identification of
      pathogenic versus (BCG-induced) protective host biomarkers and could lead to
      effective prophylactic interventions for leprosy using optimized tools for
      identification of individuals who are most at risk of developing disease. TRIAL
      REGISTRATION: Netherlands Trial Register: NTR3087.

PMID- 24088536
TI  - [A novel way to induce coronary hyperaemia].
AB  - Coronary angiography and measurement of fractional flow reserve (FFR) are used
      for anatomical and functional assessment of coronary stenoses. The achievement of
      maximal coronary hyperaemia is crucial for an accurate calculation of FFR.
      Although adenosine and papaverine have been well validated, their mechanisms of
      action as well as methods of administration have some limitations. New and better
      agents to induce hyperaemia are therefore still being sought. Currently
      regadenoson, a selective adenosine A2A receptor agonist, seems to possess the
      characteristics of the almost <ideal> hyperaemic stimulus. 

PMID- 24088535
TI  - Mindfulness based stress reduction study design of a longitudinal randomized
      controlled complementary intervention in women with breast cancer.
AB  - BACKGROUND: The stress of a breast cancer diagnosis and its treatment can produce
      a variety of psychosocial sequelae including impaired immune responses.
      Mindfulness Based Stress Reduction (MBSR) is a structured complementary program
      that incorporates meditation, yoga and mind-body exercises. Despite promising
      empirical evidence for the efficacy of MBSR, there is a need for randomized
      controlled trials (RCT). There is also a need for RCTs investigating the efficacy
      of psychosocial interventions on mood disorder and immune response in women with
      breast cancer. Therefore, the overall aim is to determine the efficacy of a
      Mindfulness Based Stress Reduction (MBSR) intervention on well-being and immune
      response in women with breast cancer. METHODS AND DESIGN: In this RCT, patients
      diagnosed with breast cancer, will consecutively be recruited to participate.
      Participants will be randomized into one of three groups: MBSR Intervention I
      (weekly group sessions + self-instructing program), MBSR Intervention II (self
      instructing program), and Controls (non-MBSR). Data will be collected before
      start of intervention, and 3, 6, and 12 months and thereafter yearly up to 5
      years. This study may contribute to evidence-based knowledge concerning the
      efficacy of MBSR to support patient empowerment to regain health in breast cancer
      disease. DISCUSSION: The present study may contribute to evidence-based knowledge
      concerning the efficacy of mindfulness training to support patient empowerment to
      regain health in a breast cancer disease. If MBSR is effective for symptom relief
      and quality of life, the method will have significant clinical relevance that may
      generate standard of care for patients with breast cancer. TRIAL REGISTRATION:
      ClinicalTrials.gov: NCT01591915.

PMID- 24088537
TI  - [Physiological and pathological roles of gangliosides].
AB  - Gangliosides are a group of glycosphingolipids that have at least one sialic acid
      residue. These lipids are structural and functional components of the external
      leaflet of the plasma membrane, particularly in neurons. Gangliosides together
      with cholesterol and sphingomyelin form lipid rafts that contain specific
      proteins involved in many important cellular processes, including signal
      transmission, cell growth and proliferation. Changes in the membrane gangliosides
      profile induce disturbances in the cell functions and finally lead to numerous
      diseases, mostly in the nervous system. The majority of such nervous system
      disorders can be recognized on the basis of analysis of the serum gangliosides
      profile and/or the presence of anti-ganglioside antibodies. Supplementation with
      exogenous gangliosides also seems to be a successful procedure for the recovery
      of ganglioside homeostasis in the neurolemma. 

PMID- 24088538
TI  - [Morphological and molecular bases of cardiac development].
AB  - The heart is a mesoderm-derived organ, whose formation is regulated by various
      genes. Initially, the most important is expression of Nkx2.5, CR1, pitx2, anf and
      mhc2a, which are responsible for differentiation of cardiomyocytes. In a later
      phase activation of mhc2b, pitx2c, mesp1, pcmf1, vmhc, xin, mcl2v, mlc2a, mlc2a,
      mef2, hand1 and hand2 was revealed. Their expression is regulated by various
      molecules, including transcription (XIN, GATA, MEF, Tbx5, Baf60c, PECAM, tie-2,
      MEF2) and growth (VEGF, FGF, PDGF) factors, as well as proteins (i.e., dickkopf
      1, cerberus, cytotactin, fibrillin, nodal, thrombomodulin, Wnt, bone morphometric
      ones - BMP2, BMP 4, BMP5, BMP7) and other substances, such as retinoid and folic
      acid. Crucial steps in cardiac organogenesis are development of the ventricle and
      atrial formation, as well as septation and valve formation. Any disturbances of
      such processes may lead to various congenital heart diseases and defects that
      could be initiated by various genetic, epigenetic or environmental factors. The
      most common heart malformations are: stenosis (coarctation) of the aorta and
      pulmonary trunk, bicuspid aortic valve, atrial and/or ventricular septal defect,
      persistent truncus arteriosus (Botallo duct), transposition of the great vessels,
      tricuspid atresia, hypoplastic left and right heart, as well as syndrome of
      Lutembachera, Cantrell, Ebstein, Eisenmenger and Shone and trilogy, tetralogy,
      pentalogy of Fallot. 

PMID- 24088539
TI  - Antioxidant activity of selected phenols estimated by ABTS and FRAP methods.
AB  - INTRODUCTION: Phenols are the most abundant compounds in nature. They are strong
      antioxidants. Too high level of free radicals leads to cell and tissue damage,
      which may cause asthma, Alzheimer disease, cancers, etc. Taking phenolics with
      the diet as supplements or natural medicines is important for homeostasis of the
      organism. MATERIALS AND METHODS: The ten most popular water soluble phenols were
      chosen for the experiment to investigate their antioxidant properties using ABTS
      radical scavenging capacity assay and ferric reducing antioxidant potential
      (FRAP) assay. RESULTS AND DISCUSSION: Antioxidant properties of selected phenols
      in the ABTS test expressed as IC50 ranged from 4.332 MUM to 852.713 MUM (for
      gallic acid and 4- hydroxyphenylacetic acid respectively). Antioxidant properties
      in the FRAP test are expressed as MUmol Fe2+/ml. All examined phenols reduced
      ferric ions at concentration 1.00 x 10-3 mg/ml. Both methods are very useful for
      determination of antioxidant capacity of water soluble phenols.

PMID- 24088540
TI  - [Adenovirus infection in immunocompromised patients].
AB  - Human adenoviruses belong to the Adenoviridae family and they are divided into
      seven species, including 56 types. Adenoviruses are common opportunistic
      pathogens that are rarely associated with clinical symptoms in immunocompetent
      patients. However, they are emerging pathogens causing morbidity and mortality in
      recipients of hematopoietic stem cell and solid organ transplants, HIV infected
      patients and patients with primary immune deficiencies. Clinical presentation
      ranges from asymptomatic viraemia to respiratory and gastrointestinal disease,
      haemorrhagic cystitis and severe disseminated illness. There is currently no
      formally approved therapy for the treatment of adenovirus infections. This
      article presents current knowledge about adenoviruses, their pathogenicity and
      information about available methods to diagnose and treat adenoviral infections. 

PMID- 24088541
TI  - [Retigabine - a new antiepileptic drug with a different mechanism of action].
AB  - Retigabine belongs to a new generation of antiepileptic drugs. Its mechanism of
      action is different from that previously known. Retigabine opens potassium
      channels of subfamily Kv 7, especially Kv 7.2 and Kv 7.3. The drug enhances GABA
      ergic transmission. It is well absorbed from the digestive system and undergoes
      metabolism via glucuronidation and acetylation. There is no interaction between
      retigabine and other antiepileptic drugs except lamotrigine. The drug has been
      registered as treatment of partial onset seizures with or without secondary
      generalization in adults. The efficacy of retigabine is being tested in other
      types of seizures and disorders characterized by neuronal hyperexcitability.
      Neuroprotective activity of retigabine is also being researched. 

PMID- 24088542
TI  - [Stem and progenitor cells in biostructure of blood vessel walls].
AB  - Development of vascular and hematopoietic systems during organogenesis occurs at
      the same time. During vasculogenesis, a small part of cells does not undergo
      complete differentiation but stays on this level, "anchored" in tissue structures
      described as stem cell niches. The presence of blood vessels within tissue stem
      cell niches is typical and led to identification of niches and ensures that they
      are functioning. The three-layer biostructure of vessel walls for artery and
      vein, tunica: intima, media and adventitia, for a long time was defined as a
      mechanical barrier between vessel light and the local tissue environment. Recent
      findings from vascular biology studies indicate that vessel walls are dynamic
      biostructures, which are equipped with stem and progenitor cells, described as
      vascular wall-resident stem cells/progenitor cells (VW-SC/PC). Distinct zones for
      vessel wall harbor heterogeneous subpopulations of VW-SC/PC, which are described
      as "subendothelial or vasculogenic zones". Recent evidence from in vitro and in
      vivo studies show that prenatal activity of stem and progenitor cells is not only
      limited to organogenesis but also exists in postnatal life, where it is
      responsible for vessel wall homeostasis, remodeling and regeneration. It is
      believed that VW-SC/PC could be engaged in progression of vascular disorders and
      development of neointima. We would like to summarize current knowledge about
      mesenchymal and progenitor stem cell phenotype with special attention to
      distribution and biological properties of VW-SC/PC in biostructures of intima,
      media and adventitia niches. It is postulated that in the near future, niches for
      VW-SC/PC could be a good source of stem and progenitor cells, especially in the
      context of vessel tissue bioengineering as a new alternative to traditional
      revascularization therapies. 

PMID- 24088543
TI  - Activity of N-acetyl-beta-D-hexosaminidase in the saliva of children with type 1
      diabetes.
AB  - BACKGROUND/AIM: Type 1 diabetes is one of the most common chronic diseases in
      children. The aim of the study was to evaluate the catabolism of glycoconjugates
      in saliva of children with type 1 diabetes, by measurement of the activity of N
      acetyl-beta-D-hexosaminidase (HEX) in their saliva. MATERIAL/METHODS: The study
      was performed in 65 children with type 1 diabetes and 39 healthy children.
      Salivary HEX activity was determined spectrophotometrically by the method of
      Zwierz et al. in the modification of Marciniak et al. Protein was determined by
      the bicinchoninic acid method (BCATM Assay Protein Kit). Concentration of the HEX
      activity was expressed in pKat/mL and HEX specific activity in pKat/MUg of
      protein. RESULTS: A significant increase in the concentration and the specific
      activity of HEX in the saliva of children with type 1 diabetes, compared to
      healthy children, was found. CONCLUSIONS: Type 1 diabetes increases salivary
      catabolism of glycoconjugates reflected by the significant increase in the
      activity of HEX in the saliva of children with type 1 diabetes compared to
      healthy children. The salivary HEX activity may be used in the diagnosis of
      children with type 1 diabetes after confirmation of our results on a larger
      cohort of children with type 1 diabetes.

PMID- 24088544
TI  - [The biological and pharmacological activity of essential oils in the treatment
      and prevention of infectious diseases].
AB  - Despite the large progress in medicine and pharmacy in the last few decades,
      traditional treatment of bacterial or viral diseases is frequently ineffective
      and is connected with some side effects. Currently, there is observed an
      increasing interest in natural plant-derived substances as a potential and
      promising group of medicines in prevention and treatment of several infectious
      diseases. Terpenes and their derivatives are a large class of natural organic
      components of essential oils and are widespread in the plant kingdom. Numerous
      experimental studies have shown that essential oils exhibit a large spectrum of
      biological and pharmacological activities in vitro. Herbal essential oils have
      been proved to possess antimicrobial, antiviral, antifungal and antiparasitic
      properties. They have also been reported to exhibit anti-inflammatory and
      immunostimulatory activities. Based on the wide spectrum of various biological
      activities, essential oils and terpenes commonly found in fruit, vegetables,
      herbs etc. have been suggested to constitute a novel group of preventive and
      therapeutic agents. Further experiments are necessary to confirm their
      pharmacological effectiveness, to determine potential toxic effects and the
      mechanism of their activity in in vivo models. This article describes the
      biological and pharmacological properties of herbal essential oils and some of
      their components, and summarizes the future prospects of potential application of
      essential oils in the prevention and treatment of infectious human diseases. In
      this review also possible mechanisms of their biological action are presented. 

PMID- 24088545
TI  - [TGF-beta signaling pathways in cancers].
AB  - TGF-beta is a multifunctional cytokine involved in growth, cell differentiation
      and maintenanceof tissue homeostasis. In addition, TGF-beta plays a key role in
      the pathogenesis of many diseases, including cancer. TGF-beta-induced signaling
      pathways have either tumor-suppression or tumor-promoting effects in a cancer
      type-specific and stage-dependent manner. TGF-beta at an early stage of cancer
      development induces signaling pathways involved in inhibitionof cell
      proliferation, induction of differentiation, apoptosis or autophagy, suppression
      of angiogenesis and inflammation. At a later stage of disease, TGF-beta exerts
      metastasis-promoting activity associated with epithelial-to-mesenchymal
      transition, modulation of cancer microenvironment and extracellular matrix
      components, inflammation and immune suppression. Furthermore, the TGF-beta
      pathways play a pivotal role in the maintenance of stem cell-like properties of
      tumor cells. The pleiotropic action of TGF-beta during tumorigenesis depends on
      interactions with different signaling pathways, including Hedgehog, WNT, PI3K-
      AKT, NOTCH, INF-gamma, TNF-alpha, and RAS-ERK. 

PMID- 24088546
TI  - [The role of sphingolipids in selected cardiovascular diseases].
AB  - Bioactive sphingolipids are engaged with numerous cellular processes such as cell
      differentiation, proliferation and apoptosis. Sphingolipid metabolism in heart is
      regulated by physical exercise and PPARs. Ceramide, the main second messenger of
      sphingomyelin pathway of signal transduction, was found to be involved in
      development of cardiac dysfunction after ischemia/reperfusion. On the other hand
      ceramide derivative sphingosine- 1- phosphate has been shown to exert potent
      cardioprotective action and guards cardiomyocytes against ischemic/reperfusion
      injury. Pharmacological compounds, which regulate metabolism of sphingolipids can
      be potentially useful in treatment of selected cardiovascular diseases. The aim
      of this work is critical review of physiological and pathological role of
      sphingolipids in circulatory system. 

PMID- 24088547
TI  - Therapy of endocrine disease: Impact of iodine supplementation in mild-to
      moderate iodine deficiency: systematic review and meta-analysis.
AB  - BACKGROUND: Although the detrimental effects of severe iodine deficiency are well
      recognised, the benefits of correcting mild-to-moderate iodine deficiency are
      uncertain. OBJECTIVES: We undertook a systematic review of the impact of iodine
      supplementation in populations with mild-to-moderate iodine deficiency. METHODS:
      We searched Medline and the Cochrane library for relevant articles published
      between January 1966 and April 2013, which investigated the effect of iodine
      supplementation on maternal and newborn thyroid function, infant neurodevelopment
      and cognitive performance in school-age children. The quality of studies was
      graded and eligible trials were evaluated in the meta-analysis. RESULTS: Nine
      randomised controlled trials (RCTs) and eight observational studies met the
      inclusion criteria. Controlled trials on infant neurodevelopment were lacking;
      gestational iodine supplementation reduced maternal thyroid volume and serum
      thyroglobulin and in some studies prevented a rise in serum thyroid-stimulating
      hormone. None of the intervention trials recorded an excess frequency of thyroid
      dysfunction in contrast to observational studies. A pooled analysis of two RCTs
      which measured cognitive function in school-age children showed modest benefits
      of iodine supplementation on perceptual reasoning (standardised mean difference
      (SMD) 0.55; 95% CI 0.05, 1.04; P=0.03) and global cognitive index (SMD 0.27; 95%
      CI 0.10, 0.44; P=0.002) with significant heterogeneity between studies.
      CONCLUSION: Iodine supplementation improves some maternal thyroid indices and may
      benefit aspects of cognitive function in school-age children, even in marginally
      iodine-deficient areas. Further large prospective controlled studies are urgently
      required to clarify these findings and quantify the risk/benefits of iodine
      supplementation in regions previously believed to be iodine sufficient such as
      the UK.

PMID- 24088548
TI  - Development of additional pituitary hormone deficiencies in pediatric patients
      originally diagnosed with idiopathic isolated GH deficiency.
AB  - OBJECTIVE: We assessed the characteristics of children initially diagnosed with
      idiopathic isolated GH deficiency (IGHD) who later developed additional
      (multiple) pituitary hormone deficiencies (MPHD). DESIGN: Data were analyzed for
      5805 pediatric patients with idiopathic IGHD, who were GH-naive at baseline and
      GH-treated in the multinational, observational Genetics and Neuroendocrinology of
      Short Stature International Study. METHODS: Development of MPHD was assessed from
      investigator diagnoses, adverse events, and concomitant medications. Analyses
      were performed for all patients and for those who developed MPHD within 4.5 years
      or had >=3.5 years, follow-up and continued to have IGHD (4-year cohort).
      RESULTS: MPHD developed in 118/5805 (2.0%) children overall, and in 96/1757
      (5.5%) in the 4-year cohort. Patients who developed MPHD had more profound GHD,
      with decreased height SDS, IGF1 SDS and peak stimulated GH, and greater height
      decrement vs target, compared with children who continued to have IGHD (P<0.001
      for each variable). Delivery complications, congenital anomalies, and
      perinatal/neonatal adverse events occurred more frequently in patients who
      developed MPHD. The most frequent additional deficiency was TSH (82 patients
      overall); four patients developed two pituitary hormone deficiencies and one
      developed three deficiencies. Multivariable logistic regression indicated that
      years of follow-up (odds ratio 1.55), baseline age (1.17), baseline height SDS
      (0.69), and peak stimulated GH (0.64) were associated with the development of
      MPHD. CONCLUSIONS: MPHD is more likely to develop in patients with more severe
      idiopathic IGHD. Older baseline age, lower baseline height SDS, and longer follow
      up duration are associated with increased risk of development of MPHD.

PMID- 24088549
TI  - Modified dynamic risk stratification for predicting recurrence using the response
      to initial therapy in patients with differentiated thyroid carcinoma.
AB  - OBJECTIVE: A new risk stratification system was proposed to estimate the risk of
      recurrence in patients with differentiated thyroid carcinoma (DTC) using the
      response to initial therapy. Here, we describe the modified dynamic risk
      stratification system, which takes into consideration the status of serum anti-Tg
      antibody (TgAb), and validate this system for assessing the risk of recurrence in
      patients with DTC. PATIENTS AND METHODS: Patients who underwent total
      thyroidectomy with radioiodine remnant ablation due to DTC between 2000 and 2005
      were included. We classified patients into four groups based on the response to
      the initial therapy ('excellent', 'acceptable', 'biochemical incomplete', and
      'structural incomplete' response). RESULTS: The median follow-up period of 715
      patients with DTC was 8 years. The response to initial therapy was an important
      risk predictor for recurrent/persistent DTC. The relative risks (95% CI) of
      recurrence were 16.5 (6.3-43.0) in the 'acceptable response' group, 41.3 (15.4
      110.8) in the 'biochemical incomplete response' group, and 281.2 (112.9-700.5) in
      the 'structural incomplete response' group compared with the 'excellent response'
      group (P<0.001, P<0.001, and P<0.001 respectively). The disease-free survival
      rate of the 'excellent response' group to initial therapy was 98.3% whereas that
      of the 'structural incomplete response' group was only 6.8%. CONCLUSIONS: Our
      study validates the usefulness of the modified dynamic risk stratification system
      including the status of serum TgAb for predicting recurrent/persistent disease in
      patients with DTC. Personalized risk assessment using the response to initial
      therapy could be useful for the follow-up and management of patients with DTC.

PMID- 24088551
TI  - We should be optimistic about ablation for atrial fibrillation.

PMID- 24088550
TI  - Giant prolactinomas in women.
AB  - OBJECTIVE: To characterise distinctive clinical features of giant prolactinomas
      in women. DESIGN: A multicentre, retrospective case series and literature review.
      METHODS: We collected data from 15 female patients with a pituitary tumour larger
      than 4 cm and prolactin levels above 1000 MUg/l and identified 19 similar cases
      from the literature; a gender-based comparison of the frequency and age
      distribution was obtained from a literature review. RESULTS: The initial PubMed
      search using the term 'giant prolactinomas' identified 125 patients (13 women)
      responding to the inclusion criteria. The female:male ratio was 1:9. Another six
      female patients were found by extending the literature search, while our own
      series added 15 patients. The median age at diagnosis was 44 years in women
      compared with 35 years in men (P<0.05). All cases diagnosed before the age of 15
      years were boys. In women (n=34), we observed a minor peak incidence during the
      third decade of life and a major peak during the fifth decade. Amenorrhoea was a
      constant feature with seven cases of primary amenorrhoea. In eight women with
      onset of secondary amenorrhoea before the age of 40 years, the diagnosis was made
      2-31 years later (median 9 years) and in all but one because of tumour pressure
      symptoms. The prolactin levels were above 10,000 MUg/l in 15/34 and misdiagnosis
      due to 'hook effect' occurred in two of them. Eighteen patients were treated with
      cabergoline; standard doses (<2.0 mg/week) were able to normalise prolactin in
      only 4/18 patients, and 7/18 patients were resistant to weekly doses ranging from
      3.0 to 7.0 mg. CONCLUSION: Giant prolactinomas are rare in women, often resistant
      to dopamine agonists and seem to be distributed in two age groups, with a larger
      late-onset peak.

PMID- 24088552
TI  - Cancer charities need access to patient data too.

PMID- 24088553
TI  - The commodification of patient medical records.

PMID- 24088554
TI  - Authors' reply to Ward.

PMID- 24088555
TI  - Trusting researchers to use open trial registers such as PROSPERO responsibly.

PMID- 24088556
TI  - The Royal College of General Practitioners replies to the BMJ.

PMID- 24088557
TI  - Clare Gerada: "It's like the wild west in healthcare". Interviewed by Gareth
      Iacobucci.

PMID- 24088558
TI  - Predicting psychopaths' violent behaviour is no better than chance, study finds.

PMID- 24088559
TI  - Prevalence of multimorbidity according to the deprivation level among the elderly
      in the Basque Country.
AB  - BACKGROUND: Multimorbidity is clearly a major challenge for healthcare systems.
      However, currently, its magnitude and impact on healthcare expenditures is still
      not well known. The objective of this paper is to present an overview of the
      prevalence of multimorbidity by deprivation level in the elderly population of
      the Basque Country. METHODS: We conducted a cross-sectional analysis that
      included all the inhabitants of the Basque Country aged 65 years and over (N =
      452,698). This was based on data from primary care electronic medical records,
      hospital admissions, and outpatient care databases, for a 4-year period. The
      health problems of the patients were identified from their diagnoses and
      prescriptions. Multimorbidity was defined as the presence of two or more chronic
      diseases out of a list of 47 of the most important and common chronic conditions
      consistent with the literature. In addition, we explored socio-economic and
      demographic variables such as age, sex, and deprivation level. RESULTS:
      Multimorbidity was found in 66.13% of the population aged 65 and over and
      increases with age until 80 years. The prevalence of multimorbidity was higher in
      deprived (69.94%) than better-off (60.22%) areas. This pattern of differences
      between the most and least disadvantaged areas was observed in all age groups and
      more marked in female (70.96-59.78%) than in male (68.54-60.86%) populations. In
      almost all diseases studied (43 out of 47), 90% of patients had been diagnosed
      with at least one other illness. It was also frequent the coexistence of mental
      and physical health problems in the same person and the presence of multiple
      physical diseases is higher in patients with mental disease than in the rest of
      population (74.97% vs. 58.14%). CONCLUSION: Multimorbidity is very common among
      people over 65 years old in the Basque Country, particularly in unfavourable
      socioeconomic environments. Given the ageing population, multimorbidity and its
      consequences should be taken into account in healthcare policy, organization of
      care and medical research. Administrative health databases are readily available
      sources of a range of information that can be useful for such purposes.

PMID- 24088560
TI  - Why ageing stops: heterogeneity explains late-life mortality deceleration in
      nematodes.
AB  - While ageing is commonly associated with exponential increase in mortality with
      age, mortality rates paradoxically decelerate late in life resulting in distinct
      mortality plateaus. Late-life mortality plateaus have been discovered in a broad
      variety of taxa, including humans, but their origin is hotly debated. One
      hypothesis argues that deceleration occurs because the individual probability of
      death stops increasing at very old ages, predicting the evolution of earlier
      onset of mortality plateaus under increased rate of extrinsic mortality. By
      contrast, heterogeneity theory suggests that mortality deceleration arises from
      individual differences in intrinsic lifelong robustness and predicts that
      variation in robustness between populations will result in differences in
      mortality deceleration. We used experimental evolution to directly test these
      predictions by independently manipulating extrinsic mortality rate (high or low)
      and mortality source (random death or condition-dependent) to create replicate
      populations of nematodes, Caenorhabditis remanei that differ in the strength of
      selection in late-life and in the level of lifelong robustness. Late-life
      mortality deceleration evolved in response to differences in mortality source
      when mortality rate was held constant, while there was no consistent response to
      differences in mortality rate. These results provide direct experimental support
      for the heterogeneity theory of late-life mortality deceleration. 

PMID- 24088561
TI  - Patterns of sperm damage in Chernobyl passerine birds suggest a trade-off between
      sperm length and integrity.
AB  - Interspecific variation in sperm size is enigmatic, but generally assumed to
      reflect species-specific trade-offs in selection pressures. Among passerine
      birds, sperm length varies sevenfold, and sperm competition risk seems to drive
      the evolution of longer sperm. However, little is known about factors favouring
      short sperm or constraining the evolution of longer sperm. Here, we report a
      comparative analysis of sperm head abnormalities among 11 species of passerine
      bird in Chernobyl, presumably resulting from chronic irradiation following the
      1986 accident. Frequencies of sperm abnormalities varied between 15.7 and 77.3%
      among species, more than fourfold higher than in uncontaminated areas.
      Nonetheless, species ranked similarly in sperm abnormalities in unpolluted areas
      as in Chernobyl, pointing to intrinsic factors underlying variation in sperm
      damage among species. Scanning electron microscopy of abnormal spermatozoa
      revealed patterns of acrosome damage consistent with premature acrosome reaction.
      Sperm length, but not sperm competition risk explained variation in sperm damage
      among species. This suggests that longer spermatozoa are more susceptible to
      premature acrosome reaction. Therefore, we hypothesize a trade-off between sperm
      length and sperm integrity affecting sperm evolution in passerine birds. 

PMID- 24088562
TI  - Diet alters species recognition in juvenile toads.
AB  - Whether environmental effects during juvenile development can alter the ontogeny
      of adult mating behaviour remains largely unexplored. We evaluated the effect of
      diet on the early expression of conspecific recognition in spadefoot toads, Spea
      bombifrons. We found that juvenile toads display phonotaxis behaviour six weeks
      post-metamorphosis. However, preference for conspecifics versus heterospecifics
      emerged later and was diet dependent. Thus, the environment can affect the early
      development of species recognition in a way that might alter adult behaviour.
      Evaluating such effects is important for understanding variation in hybridization
      between species and the nature of species boundaries.

PMID- 24088563
TI  - Infanticide as a male reproductive strategy has a nutritive risk effect in brown
      bears.
AB  - Behavioural strategies to reduce predation risk can incur costs, which are often
      referred to as risk effects. A common strategy to avoid predation is spatio
      temporal avoidance of predators, in which prey typically trade optimal resources
      for safety. Analogous with predator-prey theory, risk effects should also arise
      in species with sexually selected infanticide (SSI), in which females with
      dependent offspring avoid infanticidal males. SSI can be common in brown bear
      (Ursus arctos) populations and explains spatio-temporal segregation among
      reproductive classes. Here, we show that in a population with SSI, females with
      cubs-of-the-year had lower quality diets than conspecifics during the SSI high
      risk period, the mating season. After the mating season, their diets were of
      similar quality to diets of their conspecifics. Our results suggest a nutritive
      risk effect of SSI, in which females with cubs-of-the-year alter their resource
      selection and trade optimal resources for offspring safety. Such risk effects can
      add to female costs of reproduction and may be widespread among species with SSI.

PMID- 24088564
TI  - Longevity suppresses conflict in animal societies.
AB  - Models of social conflict in animal societies generally assume that within-group
      conflict reduces the value of a communal resource. For many animals, however, the
      primary cost of conflict is increased mortality. We develop a simple inclusive
      fitness model of social conflict that takes this cost into account. We show that
      longevity substantially reduces the level of within-group conflict, which can
      lead to the evolution of peaceful animal societies if relatedness among group
      members is high. By contrast, peaceful outcomes are never possible in models
      where the primary cost of social conflict is resource depletion. Incorporating
      mortality costs into models of social conflict can explain why many animal
      societies are so remarkably peaceful despite great potential for conflict. 

PMID- 24088565
TI  - Economic investment by ant colonies in searches for better homes.
AB  - Organisms should invest more in gathering information when the pay-off from
      finding a profitable resource is likely to be greater. Here, we ask whether
      animal societies put more effort in scouting for a new nest when their current
      one is of low quality. We measured the scouting behaviour of Temnothorax
      albipennis ant colonies when they inhabit nest-sites with different combinations
      of desirable attributes. We show that the average probability of an ant scouting
      decreases significantly with an increase in the quality of the nest in which the
      colony currently resides. This means that the greater the potential gain from
      finding a new nest, the more effort a colony puts into gathering information
      regarding new nest-sites. Our results show, for the first time to our knowledge,
      the ability of animal societies to respond collectively to the quality of a
      resource they currently have at their disposal (e.g. current nest-site) and
      regulate appropriately their information gathering efforts for finding an
      alternative (e.g. a potentially better nest-site). 

PMID- 24088566
TI  - Chlamydomonas ODA10 is a conserved axonemal protein that plays a unique role in
      outer dynein arm assembly.
AB  - Assembly of outer dynein arms (ODAs) requires multiple steps and involves
      multiple proteins in addition to dynein subunits. The Chlamydomonas ODA10, ODA5,
      and ODA8 loci genetically interact and are hypothesized to function as an
      axonemal accessory complex, but only ODA5p was previously characterized. We
      positionally cloned ODA10 and identified the gene by rescuing an oda10 mutant
      with a hemagglutinin-tagged cDNA. ODA10 sequence predicts a conserved coiled-coil
      protein homologous to mouse ccdc151. ODA10p is present in cytoplasm and flagella,
      remains axonemal after detergent treatment, and is extracted with 0.6 M NaCl.
      Both outer arm dynein and ODA10p rebound to the axonemes when desalted extracts
      are mixed with oda10-mutant axonemes. Sucrose gradient separation of these
      extracts shows that ODA10p sediments near the top of the gradient, not with 23S
      outer dynein arm proteins. Unexpectedly, dynein and ODA10p fractions are able to
      bind individually to oda10 axonemes. ODA10p is present on oda8-mutant flagella at
      wild-type levels. However, ODA10p does not assemble into oda5 flagella and is
      absent from oda5 cytoplasm, suggesting a necessity of ODA5p for stability of
      ODA10p in vivo. The results suggest that ODA10p does not function as a part of a
      traditionally defined docking complex.

PMID- 24088567
TI  - Supervillin binding to myosin II and synergism with anillin are required for
      cytokinesis.
AB  - Cytokinesis, the process by which cytoplasm is apportioned between dividing
      daughter cells, requires coordination of myosin II function, membrane
      trafficking, and central spindle organization. Most known regulators act during
      late cytokinesis; a few, including the myosin II-binding proteins anillin and
      supervillin, act earlier. Anillin's role in scaffolding the membrane cortex with
      the central spindle is well established, but the mechanism of supervillin action
      is relatively uncharacterized. We show here that two regions within supervillin
      affect cell division: residues 831-1281, which bind central spindle proteins, and
      residues 1-170, which bind the myosin II heavy chain (MHC) and the long form of
      myosin light-chain kinase. MHC binding is required to rescue supervillin
      deficiency, and mutagenesis of this site creates a dominant-negative phenotype.
      Supervillin concentrates activated and total myosin II at the furrow, and
      simultaneous knockdown of supervillin and anillin additively increases cell
      division failure. Knockdown of either protein causes mislocalization of the
      other, and endogenous anillin increases upon supervillin knockdown. Proteomic
      identification of interaction partners recovered using a high-affinity green
      fluorescent protein nanobody suggests that supervillin and anillin regulate the
      myosin II and actin cortical cytoskeletons through separate pathways. We conclude
      that supervillin and anillin play complementary roles during vertebrate
      cytokinesis. 

PMID- 24088569
TI  - The tethering complex HOPS catalyzes assembly of the soluble SNARE Vam7 into
      fusogenic trans-SNARE complexes.
AB  - The fusion of yeast vacuolar membranes depends on the disassembly of cis-soluble
      N-ethylmaleimide-sensitive factor attachment protein receptor (SNARE) complexes
      and the subsequent reassembly of new SNARE complexes in trans. The disassembly of
      cis-SNARE complexes by Sec17/Sec18p releases the soluble SNARE Vam7p from
      vacuolar membranes. Consequently, Vam7p needs to be recruited to the membrane at
      future sites of fusion to allow the formation of trans-SNARE complexes. The
      multisubunit tethering homotypic fusion and vacuole protein sorting (HOPS)
      complex, which is essential for the fusion of vacuolar membranes, was previously
      shown to have direct affinity for Vam7p. The functional significance of this
      interaction, however, has been unclear. Using a fully reconstituted in vitro
      fusion reaction, we now show that HOPS facilitates membrane fusion by recruiting
      Vam7p for fusion. In the presence of HOPS, unlike with other tethering agents,
      very low levels of added Vam7p suffice to induce vigorous fusion. This is a
      specific recruitment of Vam7p rather than an indirect stimulation of SNARE
      complex formation through tethering, as HOPS does not facilitate fusion with a
      low amount of a soluble form of another vacuolar SNARE, Vti1p. Our findings
      establish yet another function among the multiple tasks that HOPS performs to
      catalyze the fusion of yeast vacuoles. 

PMID- 24088568
TI  - Wnt5a signaling promotes apical and basolateral polarization of single epithelial
      cells.
AB  - Single epithelial-derived tumor cells have been shown to induce apical and
      basolateral (AB) polarity by expression of polarization-related proteins.
      However, physiological cues and molecular mechanisms for AB polarization of
      single normal epithelial cells are unclear. When intestinal epithelial cells 6
      (IEC6 cells) were seeded on basement membrane proteins (Matrigel), single cells
      formed an F-actin cap on the upper cell surface, where apical markers
      accumulated, and a basolateral marker was localized to the rest of the cell
      surface region, in a Wnt5a signaling-dependent manner. However, these phenotypes
      were not induced by type I collagen. Rac1 activity in the noncap region was
      higher than that in the cap region, whereas Rho activity increased toward the cap
      region. Wnt5a signaling activated and inhibited Rac1 and RhoA, respectively,
      independently through Tiam1 and p190RhoGAP-A, which formed a tertiary complex
      with Dishevelled. Furthermore, Wnt5a signaling through Rac1 and RhoA was required
      for cystogenesis of IEC6 cells. These results suggest that Wnt5a promotes the AB
      polarization of IEC6 cells through regulation of Rac and Rho activities in a
      manner dependent on adhesion to specific extracellular matrix proteins.

PMID- 24088570
TI  - Key events during the transition from rapid growth to quiescence in budding yeast
      require posttranscriptional regulators.
AB  - Yeast that naturally exhaust the glucose from their environment differentiate
      into three distinct cell types distinguishable by flow cytometry. Among these is
      a quiescent (Q) population, which is so named because of its uniform but readily
      reversed G1 arrest, its fortified cell walls, heat tolerance, and longevity.
      Daughter cells predominate in Q-cell populations and are the longest lived. The
      events that differentiate Q cells from nonquiescent (nonQ) cells are initiated
      within hours of the diauxic shift, when cells have scavenged all the glucose from
      the media. These include highly asymmetric cell divisions, which give rise to
      very small daughter cells. These daughters modify their cell walls by Sed1- and
      Ecm33-dependent and dithiothreitol-sensitive mechanisms that enhance Q-cell
      thermotolerance. Ssd1 speeds Q-cell wall assembly and enables mother cells to
      enter this state. Ssd1 and the related mRNA-binding protein Mpt5 play critical
      overlapping roles in Q-cell formation and longevity. These proteins deliver mRNAs
      to P-bodies, and at least one P-body component, Lsm1, also plays a unique role in
      Q-cell longevity. Cells lacking Lsm1 and Ssd1 or Mpt5 lose viability under these
      conditions and fail to enter the quiescent state. We conclude that
      posttranscriptional regulation of mRNAs plays a crucial role in the transition in
      and out of quiescence. 

PMID- 24088571
TI  - Arf-like GTPase Arl8b regulates lytic granule polarization and natural killer
      cell-mediated cytotoxicity.
AB  - Natural killer (NK) lymphocytes contain lysosome-related organelles (LROs), known
      as lytic granules, which upon formation of immune synapse with the target cell,
      polarize toward the immune synapse to deliver their contents to the target cell
      membrane. Here, we identify a small GTP-binding protein, ADP-ribosylation factor
      like 8b (Arl8b), as a critical factor required for NK cell-mediated cytotoxicity.
      Our findings indicate that Arl8b drives the polarization of lytic granules and
      microtubule-organizing centers (MTOCs) toward the immune synapse between effector
      NK lymphocytes and target cells. Using a glutathione S-transferase pull-down
      approach, we identify kinesin family member 5B (KIF5B; the heavy chain of kinesin
      1) as an interaction partner of Arl8b from NK cell lysates. Previous studies
      showed that interaction between kinesin-1 and Arl8b is mediated by SifA and
      kinesin-interacting protein (SKIP) and the tripartite complex drives the
      anterograde movement of lysosomes. Silencing of both KIF5B and SKIP in NK cells,
      similar to Arl8b, led to failure of MTOC-lytic granule polarization to the immune
      synapse, suggesting that Arl8b and kinesin-1 together control this critical step
      in NK cell cytotoxicity.

PMID- 24088572
TI  - Functional overlap among distinct G1/S inhibitory pathways allows robust G1
      arrest by yeast mating pheromones.
AB  - In budding yeast, mating pheromones arrest the cell cycle in G1 phase via a
      pheromone-activated Cdk-inhibitor (CKI) protein, Far1. Alternate pathways must
      also exist, however, because deleting the cyclin CLN2 restores pheromone arrest
      to far1 cells. Here we probe whether these alternate pathways require the G1/S
      transcriptional repressors Whi5 and Stb1 or the CKI protein Sic1, whose metazoan
      analogues (Rb or p27) antagonize cell cycle entry. Removing Whi5 and Stb1 allows
      partial escape from G1 arrest in far1 cln2 cells, along with partial derepression
      of G1/S genes, which implies a repressor-independent route for inhibiting G1/S
      transcription. This route likely involves pheromone-induced degradation of Tec1,
      a transcriptional activator of the cyclin CLN1, because Tec1 stabilization also
      causes partial G1 escape in far1 cln2 cells, and this is additive with Whi5/Stb1
      removal. Deleting SIC1 alone strongly disrupts Far1-independent G1 arrest,
      revealing that inhibition of B-type cyclin-Cdk activity can empower weak arrest
      pathways. Of interest, although far1 cln2 sic1 cells escaped G1 arrest, they lost
      viability during pheromone exposure, indicating that G1 exit is deleterious if
      the arrest signal remains active. Overall our findings illustrate how multiple
      distinct G1/S-braking mechanisms help to prevent premature cell cycle commitment
      and ensure a robust signal-induced G1 arrest. 

PMID- 24088573
TI  - mTOR regulates phagosome and entotic vacuole fission.
AB  - Macroendocytic vacuoles formed by phagocytosis, or the live-cell engulfment
      program entosis, undergo sequential steps of maturation, leading to the fusion of
      lysosomes that digest internalized cargo. After cargo digestion, nutrients must
      be exported to the cytosol, and vacuole membranes must be processed by mechanisms
      that remain poorly defined. Here we find that phagosomes and entotic vacuoles
      undergo a late maturation step characterized by fission, which redistributes
      vacuolar contents into lysosomal networks. Vacuole fission is regulated by the
      serine/threonine protein kinase mammalian target of rapamycin complex 1 (mTORC1),
      which localizes to vacuole membranes surrounding engulfed cells. Degrading
      engulfed cells supply engulfing cells with amino acids that are used in
      translation, and rescue cell survival and mTORC1 activity in starved macrophages
      and tumor cells. These data identify a late stage of phagocytosis and entosis
      that involves processing of large vacuoles by mTOR-regulated membrane fission. 

PMID- 24088574
TI  - The BCL2-938 C > A promoter polymorphism is associated with risk group
      classification in children with acute lymphoblastic leukemia.
AB  - BACKGROUND: Acute lymphoblastic leukemia (ALL) is the most common pediatric
      cancer. While current treatment regimens achieve almost 80% overall survival,
      long-term side effects of chemotherapeutic agents can be severe. The functional
      BCL2-938C > A promoter polymorphism is known to influence the balance between
      survival and apoptosis of malignant hematolymphoid cells. We investigated its
      usefulness as a marker for treatment stratification for children with ALL.
      METHODS: We analyzed DNA from 182 children suffering from ALL in this study to
      determine genotypes of the -938 C > A polymorphism by "slow-down" PCR. RESULTS:
      ALL patients with the BCL2-938CC genotype had an approximately 3-fold higher risk
      of belonging to a high-risk group. Within the high-risk group, 50% of BCL2-938CC
      patients were classified as high-risk due to poor prednisone response whereas
      only 33% of patients with AC and AA genotypes were classified as high-risk for
      the same reason. CONCLUSIONS: Our results suggest that BCL2-938C > A genotyping
      may be beneficial for therapy response prediction in ALL patients, and warrant
      examination in a larger cohort to validate its usefulness for treatment
      stratification of pediatric ALL patients.

PMID- 24088575
TI  - Oxidative stress and apoptosis in a pig model of brain death (BD) and living
      donation (LD).
AB  - BACKGROUND: As organ shortage is increasing, the acceptance of marginal donors
      increases, which might result in poor organ function and patient survival.
      Mostly, organ damage is caused during brain death (BD), cold ischemic time (CIT)
      or after reperfusion due to oxidative stress or the induction of apoptosis. The
      aim of this study was to study a panel of genes involved in oxidative stress and
      apoptosis and compare these findings with immunohistochemistry from a BD and
      living donation (LD) pig model and after cold ischemia time (CIT). METHODS: BD
      was induced in pigs; after 12 h organ retrieval was performed; heart, liver and
      kidney tissue specimens were collected in the BD (n = 6) and in a LD model (n =
      6). PCR analysis for NFKB1, GSS, SOD2, PPAR-alpha, OXSR1, BAX, BCL2L1, and HSP
      70.2 was performed and immunohistochemistry used to show apoptosis and
      nitrosative stress induced cell damage. RESULTS: In heart tissue of BD BAX,
      BCL2L1 and HSP 70.2 increased significantly after CIT. Only SOD2 was over
      expressed after CIT in BD liver tissue. In kidney tissue, BCL2L1, NFKB, OXSR1,
      SOD2 and HSP 70.2 expression was significantly elevated in LD.
      Immunohistochemistry showed a significant increase in activated Caspase 3 and
      nitrotyrosine positive cells after CIT in BD in liver and in kidney tissue but
      not in heart tissue. CONCLUSION: The up-regulation of protective and apoptotic
      genes seems to be divergent in the different organs in the BD and LD setting;
      however, immunohistochemistry revealed more apoptotic and nitrotyrosine positive
      cells in the BD setting in liver and kidney tissue whereas in heart tissue both
      BD and LD showed an increase.

PMID- 24088576
TI  - Mixed neuronal-glial tumor in the temporal lobe of an infant: a case report.
AB  - BACKGROUND: Tumors that arise in the temporal lobes of infants and spread to the
      neural system are limited to several diagnoses. Herein, we present an infantile
      case of a temporal tumor showing neuronal and glial differentiation. CASE
      PRESENTATION: The patient was a 9-month-old boy with low body weight due to
      intrauterine growth retardation. At 9 months after birth, he presented partial
      seizures. Computed tomography scanning revealed a mass (35 * 40 mm) in the left
      temporal lobe. Isointensity was noted on magnetic resonance T1-weighted images
      and fluid attenuation inversion recovery images. The tumor was heterogeneously
      enhanced with gadolinium. Positron emission tomography showed high methionine
      uptake in the tumor. During surgery, the tumor, which was elastic and soft and
      bled easily, was gross totally resected. A moderately clear boundary was noted
      between the tumor and normal brain parenchyma. Histologically, the tumor mainly
      comprised a ganglioglioma-like portion and short spindle cells at different
      densities. The former was immunohistochemically positive for some kinds of
      neuronal markers including synaptophysin. The spindle cells were positive for
      glial fibrillary acidic protein, but desmoplasia was not observed. DISCUSSION:
      The tumor contained both neuronal and glial elements; the former were the main
      constituents of the tumor and included several ganglion-like cells. Because
      neuronal elements gradually transited to glial cells, a mixed neuronal-glial
      tumor was diagnosed. VIRTUAL SLIDES: The virtual slide(s) for this article can be
      found here: http://www.diagnosticpathology.diagnomx.eu/vs/2045126100982604.

PMID- 24088577
TI  - Pulmonary sarcomatoid carcinoma: a clinicopathologic study and prognostic
      analysis of 51 cases.
AB  - BACKGROUND: Pulmonary sarcomatoid carcinoma is a diagnostically challenging group
      of tumors. It's a rare histologic subtype of non-small cell lung cancer.There are
      five subgroups of pulmonary sarcomatoid carcinoma, they are identified as
      pleomorphic carcinoma, spindle cell carcinoma, giant cell carcinoma,
      carcinosarcoma, and pulmonary blastoma. We explored the clinicopathologic
      features and prognostic factors of this tumor. METHODS: We analyzed
      retrospectively the clinicopathological data of 51 patients with pulmonary
      sarcomatoid carcinoma who were treated in the First Affiliated Hospital of
      Zhengzhou University, Henan Cancer Hospital and Henan People Hospital from
      January 2005 to December 2012. The correlation between prognosis and age, sex,
      smoking history, tumor size, TNM staging, and treatment modality was analyzed by
      the statistical software SPSS 17.0. The survival analysis was conducted using the
      Kaplan-Meier method. The factors influencing survival were analyzed using
      univariate (Log-rank) and multivariate (Cox) models. RESULTS: The overall
      survival rates at 1, 2, 3 and 5 years were 45.5%, 35.8%, 28.2% and 20.1%,
      respectively. Cox univariate analyses revealed that age, tumor size, T stage, M
      stage, surgery or not, and postoperative chemotherapy or not, were prognostic
      factors. Cox multivariate analysis found that tumor size and M stage were
      independent prognostic factors for PSC. CONCLUSIONS: Due to its rarity and the
      lack of large-scale clinical trial evidence, few studies about PSC have been
      reported, its clinical and pathological characteristics remain unclear, and its
      preoperative diagnosis and investigation of novel treatment approaches are
      imperative. In our study, the main factors affecting the prognosis of tumor size
      and M staging are the crucial prognostic factors for PSC. Surgical resection and
      postoperative adjuvant chemotherapy might result in better prognosis.

PMID- 24088578
TI  - Impact of CYP2C19 polymorphism on platelet function tests and coagulation and
      inflammatory biomarkers in patients undergoing percutaneous coronary
      intervention.
AB  - AIM: Carriers of the reduced-function CYP2C19 allele receiving dual antiplatelet
      therapy (DAPT) with aspirin and clopidogrel exhibit diminished platelet
      inhibition and an increased risk of events. The purpose of this study was to
      investigate the effects of CYP2C19 gene variants on platelet function tests and
      coagulation and inflammatory biomarkers in patients undergoing elective
      percutaneous coronary intervention (PCI). METHODS: This prospective,
      observational, multicenter study enrolled 104 consecutive Japanese patients
      undergoing elective PCI. We examined the CYP2C19 genotype, platelet function
      tests, the levels of coagulation and inflammatory biomarkers and the serum levels
      of high-sensitivity troponin T (hs-TnT) before, immediately after and one, two
      and 28 days after PCI. RESULTS: A total of 68 (65%) of the 104 enrolled patients
      were carriers of the CYP2C19 reducedfunction allele. On-clopidogrel platelet
      aggregation (PA), measured using light transmittance aggregometry and the
      VerifyNow((r)) P2Y12 system, and the platelet reactivity index (PRI) were
      significantly higher at all time points in the carriers than in the noncarriers
      (p<0.05), whereas there were no differences in the levels of the coagulation and
      inflammatory biomarkers or serum hs-TnT. Simple and multiple logistic regression
      analyses identified on-clopidogrel PA and PRI as being significant predictors of
      carriers of the CYP2C19 reduced-function allele. CONCLUSIONS: The present study
      suggests that platelet function tests, but not coagulation, inflammatory or
      cardiac biomarkers, are useful for identifying carriers of CYP2C19 reduced
      function gene variants and monitoring the efficacy of DAPT in patients undergoing
      elective PCI.

PMID- 24088579
TI  - An Intelligent Automation Platform for Rapid Bioprocess Design.
AB  - Bioprocess development is very labor intensive, requiring many experiments to
      characterize each unit operation in the process sequence to achieve product
      safety and process efficiency. Recent advances in microscale biochemical
      engineering have led to automated experimentation. A process design workflow is
      implemented sequentially in which (1) a liquid-handling system performs high
      throughput wet lab experiments, (2) standalone analysis devices detect the data,
      and (3) specific software is used for data analysis and experiment design given
      the user's inputs. We report an intelligent automation platform that integrates
      these three activities to enhance the efficiency of such a workflow. A multiagent
      intelligent architecture has been developed incorporating agent communication to
      perform the tasks automatically. The key contribution of this work is the
      automation of data analysis and experiment design and also the ability to
      generate scripts to run the experiments automatically, allowing the elimination
      of human involvement. A first-generation prototype has been established and
      demonstrated through lysozyme precipitation process design. All procedures in the
      case study have been fully automated through an intelligent automation platform.
      The realization of automated data analysis and experiment design, and automated
      script programming for experimental procedures has the potential to increase lab
      productivity. 

PMID- 24088580
TI  - A High-Temperature, High-Throughput Method for Monitoring Residual Formaldehyde
      in Vaccine Formulations.
AB  - Formaldehyde has long been used in the chemical inactivation of viral material
      during vaccine production. Viral inactivation is required so that the vaccine
      does not infect the patient. Formaldehyde is diluted during the vaccine
      manufacturing process, but residual quantities of formaldehyde are still present
      in some current vaccines. Although formaldehyde is considered safe for use in
      vaccines by the Food and Drug Administration, excessive exposure to this chemical
      may lead to cancer or other health-related issues. An assay was developed that is
      capable of detecting levels of residual formaldehyde in influenza vaccine
      samples. The assay employs incubation of dosage formulation suspensions with
      hydralazine hydrochloride under mildly acidic conditions and elevated
      temperatures, where formaldehyde is derivatized to yield fluorescent s-triazolo
      [3,4-a]-phthalazine. The assay has been traditionally run by high-performance
      liquid chromatography, where runtimes of 15 minutes per sample can be expected.
      Our laboratory has developed a plate-based version that drastically improved the
      throughput to a runtime of 96 samples per minute. The assay was characterized and
      validated with respect to reaction temperature, evaporation, stability, and
      selectivity to monitor residual formaldehyde in various influenza vaccine
      samples, including in-process samples. Heat transfer and evaporation will be
      especially considered in this work. Since the assay is plate based, it is
      automation friendly. The new assay format has attained detection limits of 0.01
      ug/mL residual formaldehyde, which is easily able to detect and quantify
      formaldehyde at levels used in many current vaccine formulations (<5 ug/0.5-mL
      dose). 

PMID- 24088581
TI  - Rapid and Sensitive Detection of H1N1/2009 Virus from Aerosol Samples with a
      Microfluidic Immunosensor.
AB  - Influenza A H1N1/2009 is a highly infectious, rapidly spreading airborne disease
      that needs to be monitored in near real time, preferably in a microfluidic
      format. However, such demonstration is difficult to find as H1N1 concentration in
      aerosol samples is extremely low, with interference from dust particles. In this
      work, we measured Mie scatter intensities from a microfluidic device with optical
      waveguide channels, where the antibody-conjugated latex beads immunoagglutinated
      with the target H1N1 antigens. Through careful optimizations of optical
      parameters, we were able to maximize the Mie scatter increase from the latex
      immunoagglutinations while minimizing the background scatter from the dust
      particles. The aerosol samples were collected from a 1:10 mock classroom using a
      button air sampler, where a nebulizer generated aerosols, simulating human
      coughing. The detection limits with real aerosol samples were 1 and 10 pg/mL,
      using a spectrometer or a cell phone camera as an optical detector, respectively.
      These are several orders of magnitudes more sensitive than the other methods. The
      microfluidic immunosensor readings are in concordance with the results of reverse
      transcription polymerase chain reaction. The assay time was 30 s for sampling and
      5 min for the microfluidic assay. 

PMID- 24088583
TI  - Bustling argon: biological effect.
AB  - Argon is a noble gas in group 18 of the periodic table. Certificated to exist in
      air atmosphere merely one century ago, discovery of argon shows interesting
      stories of researching and exploring. It was assumed to have no chemical
      activity. However, argon indeed present its biological effect on mammals.
      Narcotic effect of argon in diving operation and neur-protective function of
      argon in cerebral injury demonstrate that argon has crucial effect and be
      concentrated on is necessary. Furthermore, consider to be harmless to human,
      argon clinical application in therapy would be another option. 

PMID- 24088582
TI  - Reconstruction of the experimentally supported human protein interactome: what
      can we learn?
AB  - BACKGROUND: Understanding the topology and dynamics of the human protein-protein
      interaction (PPI) network will significantly contribute to biomedical research,
      therefore its systematic reconstruction is required. Several meta-databases
      integrate source PPI datasets, but the protein node sets of their networks vary
      depending on the PPI data combined. Due to this inherent heterogeneity, the way
      in which the human PPI network expands via multiple dataset integration has not
      been comprehensively analyzed. We aim at assembling the human interactome in a
      global structured way and exploring it to gain insights of biological relevance.
      RESULTS: First, we defined the UniProtKB manually reviewed human "complete"
      proteome as the reference protein-node set and then we mined five major source
      PPI datasets for direct PPIs exclusively between the reference proteins. We
      updated the protein and publication identifiers and normalized all PPIs to the
      UniProt identifier level. The reconstructed interactome covers approximately 60%
      of the human proteome and has a scale-free structure. No apparent differentiating
      gene functional classification characteristics were identified for the
      unrepresented proteins. The source dataset integration augments the network
      mainly in PPIs. Polyubiquitin emerged as the highest-degree node, but the
      inclusion of most of its identified PPIs may be reconsidered. The high number
      (>300) of connections of the subsequent fifteen proteins correlates well with
      their essential biological role. According to the power-law network structure,
      the unrepresented proteins should mainly have up to four connections with equally
      poorly-connected interactors. CONCLUSIONS: Reconstructing the human interactome
      based on the a priori definition of the protein nodes enabled us to identify the
      currently included part of the human "complete" proteome, and discuss the role of
      the proteins within the network topology with respect to their function. As the
      network expansion has to comply with the scale-free theory, we suggest that the
      core of the human interactome has essentially emerged. Thus, it could be employed
      in systems biology and biomedical research, despite the considerable number of
      currently unrepresented proteins. The latter are probably involved in specialized
      physiological conditions, justifying the scarcity of related PPI information, and
      their identification can assist in designing relevant functional experiments and
      targeted text mining algorithms.

PMID- 24088584
TI  - Elongated nanostructures for radial junction solar cells.
AB  - In solar cell technology, the current trend is to thin down the active absorber
      layer. The main advantage of a thinner absorber is primarily the reduced
      consumption of material and energy during production. For thin film silicon (Si)
      technology, thinning down the absorber layer is of particular interest since both
      the device throughput of vacuum deposition systems and the stability of the
      devices are significantly enhanced. These features lead to lower cost per
      installed watt peak for solar cells, provided that the (stabilized) efficiency is
      the same as for thicker devices. However, merely thinning down inevitably leads
      to a reduced light absorption. Therefore, advanced light trapping schemes are
      crucial to increase the light path length. The use of elongated nanostructures is
      a promising method for advanced light trapping. The enhanced optical performance
      originates from orthogonalization of the light's travel path with respect to the
      direction of carrier collection due to the radial junction, an improved anti
      reflection effect thanks to the three-dimensional geometric configuration and the
      multiple scattering between individual nanostructures. These advantages
      potentially allow for high efficiency at a significantly reduced quantity and
      even at a reduced material quality, of the semiconductor material. In this
      article, several types of elongated nanostructures with the high potential to
      improve the device performance are reviewed. First, we briefly introduce the
      conventional solar cells with emphasis on thin film technology, following the
      most commonly used fabrication techniques for creating nanostructures with a high
      aspect ratio. Subsequently, several representative applications of elongated
      nanostructures, such as Si nanowires in realistic photovoltaic (PV) devices, are
      reviewed. Finally, the scientific challenges and an outlook for nanostructured PV
      devices are presented. 

PMID- 24088585
TI  - Enhancing the role of doctors in preventing suicide.

PMID- 24088586
TI  - Report on the 2013 Readers Survey.

PMID- 24088587
TI  - Attitudes towards suicide following an undergraduate suicide prevention module:
      experience of medical students in Hong Kong.
AB  - OBJECTIVES: To explore qualitative and quantitative changes in attitudes and
      experiences of medical students following a special study suicide prevention
      module. DESIGN: Pilot study. SETTING: The University of Hong Kong, Hong Kong.
      PARTICIPANTS: A 2-week intensive special studies module was delivered to third-
      and fourth-year medical students in June 2011. The module was elective and
      involved several modes of teaching. All students filled the Chinese Attitude
      toward Suicide Questionnaire before and after the course. They also provided
      written feedback about the module experience. Three students participated in in
      depth interviews. RESULTS: In all, 22 students aged 20 to 23 years enrolled in
      the special studies module; 15 (68%) of whom were male and only one was married.
      Positive trends were noted in attitudes towards suicide following the
      participation in the special studies module, namely, reduced negative appraisal
      of suicide, reduced stigmatisation of the phenomena, and increased sensitivity to
      suicide-related facts. Feedback of the students suggested inclusion of this
      module into the main medical curriculum, increased confidence in dealing with
      issues related to suicide, and appreciation of skills focusing on interviewing in
      patients. Overall the module was well received by medical students. CONCLUSIONS:
      A suicide prevention training module seems to have been valued by students and
      lead to positive attitudes towards understanding suicide. Adopting this
      initiative as a suicide prevention strategy warrants further exploration.

PMID- 24088588
TI  - Factors affecting implementation of accreditation programmes and the impact of
      the accreditation process on quality improvement in hospitals: a SWOT analysis.
AB  - OBJECTIVES: The objectives of this review were to identify factors that influence
      implementation of hospital accreditation programmes and to assess the impact of
      the accreditation process on quality improvement in public hospitals. DATA
      SOURCES: Two electronic databases, Medline (OvidSP) and PubMed, were
      systematically searched. STUDY SELECTION: "Public hospital", "hospital
      accreditation", and "quality improvement" were used as the search terms. A total
      of 348 citations were initially identified. After critical appraisal and study
      selection, 26 articles were included in the review. DATA EXTRACTION: The data
      were extracted and analysed using a SWOT (strengths, weaknesses, opportunities,
      threats) analysis. DATA SYNTHESIS: Increased staff engagement and communication,
      multidisciplinary team building, positive changes in organisational culture, and
      enhanced leadership and staff awareness of continuous quality improvement were
      identified as strengths. Weaknesses included organisational resistance to change,
      increased staff workload, lack of awareness about continuous quality improvement,
      insufficient staff training and support for continuous quality improvement, lack
      of applicable accreditation standards for local use, and lack of performance
      outcome measures. Opportunities included identification of improvement areas,
      enhanced patient safety, additional funding, public recognition, and market
      advantage. Threats included opportunistic behaviours, funding cuts, lack of
      incentives for participation, and a regulatory approach to mandatory
      participation. CONCLUSIONS: By relating the findings to the operational issues of
      accreditation, this review discussed the implications for successful
      implementation and how accreditation may drive quality improvement. These
      findings have implications for various stakeholders (government, the public,
      patients and health care providers), when it comes to embarking on accreditation
      exercises.

PMID- 24088589
TI  - Ectopia cordis.
AB  - We report on a preterm male newborn with complete ectopia cordis associated with
      Cantrell's syndrome. The neonate had an ectopia cordis involving defects of the
      lower sternum, supraumbilical abdominal wall, anterior portion of the diaphragm,
      and diaphragmatic portion of the pericardium associated with complex congenital
      heart defects. The infant died shortly after birth. We discuss this case and
      review the literature. 

PMID- 24088590
TI  - Erdheim-Chester disease: an uncommon cause of upper urinary tract obstruction.
AB  - Erdheim-Chester disease is a rare non-Langerhans form of systemic histiocytosis
      of unknown origin. We describe a 45-year-old man presenting with bilateral
      hydronephrosis suggestive of extrinsic urinary tract obstruction. Computed
      tomography revealed extensive hypodense soft tissue infiltration in the
      retroperitoneum surrounding the kidneys. Needle biopsy of the retroperitoneal
      soft tissue revealed aggregates of lipid-laden histiocytes expressing CD68 but
      negative for CD1a and S100 protein. The diagnosis of Erdheim-Chester disease was
      supported by typical radionuclide bone scinitigraphic findings. Treatment with
      prednisolone, sirolimus, and regular ureteric stent revision was initiated to
      achieve adequate urinary tract drainage. To our knowledge, this is the second
      patient with Erdheim-Chester disease reported in Hong Kong. A high index of
      suspicion is required to avoid delay in the diagnosis of this rare disease. 

PMID- 24088591
TI  - Metastatic carcinoma of breast in the urinary bladder.
AB  - Less than 5% of breast cancers present as metastasis, and urinary bladder
      secondaries were only sporadically reported in the literature. However, they may
      even be responsible for the initial presentation, for which reason they can pose
      a diagnostic challenge. We present here what we believe is the first such case in
      Hong Kong, with a review of this entity. 

PMID- 24088592
TI  - Anterior mediastinal alveolar rhabdomyosarcoma in an infant: rare site for a
      common paediatric tumour.
AB  - Rhabdomyosarcoma is a common paediatric soft tissue tumour. However, the anterior
      mediastinum is an extremely rare site for its occurrence. This report describes
      the imaging and histological findings of such a tumour in a 4-month-old boy. 

PMID- 24088593
TI  - Reverse survivor bias in observational studies involving cohorts: a lesson from
      '1:1' trauma studies.

PMID- 24088594
TI  - Anaemia and type 2 diabetes.

PMID- 24088595
TI  - Authors' reply.

PMID- 24088596
TI  - On the aetiology of the secondary psoas abscesses.

PMID- 24088597
TI  - Brunner's gland adenoma: unusual cause of duodenal haemorrhage and obstruction.

PMID- 24088598
TI  - A woman with a painful hip after a splits.

PMID- 24088600
TI  - Low skeletal muscle mass is associated with insulin resistance, diabetes, and
      metabolic syndrome in the Korean population: the Korea National Health and
      Nutrition Examination Survey (KNHANES) 2009-2010.
AB  - Sarcopenia is an emerging risk factor for metabolic disorders. No study of the
      association of sarcopenia with insulin resistance, diabetes, and metabolic
      syndrome (MS) according to age group and obesity status in the general population
      has been reported. We investigated these associations in the Korean population.
      Participants included 4558 males and 5874 females, who were >=20 years of age or
      older from the fourth and fifth Korea National Health and Nutritional Examination
      Surveys of the Korean population (2009 and 2010). Age was categorized according
      to three groups (20-39, 40-59, and >= 60 years). Obesity was defined according to
      body mass index. Sarcopenia was defined as the appendicular skeletal muscle mass
      (ASM) divided by weight (Wt) (%) of > 2SD below the sex-specific mean for young
      adults. Homeostasis model assessment of insulin resistance (HOMA-IR) was
      calculated. After adjustment for confounding variables, sarcopenia showed a
      significant association with HOMA-IR in the non-obese group (P<0.001). Sarcopenia
      was found to be a risk factor for diabetes in the non-obese group (OR, 2.140; 95%
      CI, 1.549-2.956; P<0.001). Sarcopenia also showed an association with MS in the
      non-obese group (OR, 2.209; 95% CI, 1.679-2.906; P<0.001), but not in the obese
      group. However, these results were not relevant to young age group. In
      conclusion, sarcopenia showed an association with insulin resistance, diabetes,
      and MS, in the non-obese population. Sarcopenia may be an early predictor for
      diabetes and MS susceptibility in the non-obese population, particularly in
      elderly people. 

PMID- 24088599
TI  - piRNAs and epigenetic conversion in Drosophila.
AB  - Transposable element (TE) activity is repressed in the Drosophila germline by
      Piwi-Interacting RNAs (piRNAs), a class of small non-coding RNAs. These piRNAs
      are produced by discrete genomic loci containing TE fragments. In a recent
      publication, we tested for the existence of a strict epigenetic induction of
      piRNA production capacity by a locus in the D. melanogaster genome. We used 2
      lines carrying a transgenic 7-copy tandem cluster (P-lacZ-white) at the same
      genomic site. This cluster generates in both lines a local heterochromatic
      sector. One line (T-1) produces high levels of ovarian piRNAs homologous to the P
      lacZ-white transgenes and shows a strong capacity to repress homologous sequences
      in trans, whereas the other line (BX2) is devoid of both of these capacities. The
      properties of these 2 lines are perfectly stable over generations. We have shown
      that the maternal transmission of a cytoplasm carrying piRNAs from the first line
      can confer to the inert transgenic locus of the second, a totally de novo
      capacity to produce high levels of piRNAs as well as the ability to induce
      homology-dependent silencing in trans. These new properties are stably inherited
      over generations (n>50). Furthermore, the converted locus has itself become able
      to convert an inert transgenic locus via cytoplasmic maternal inheritance. This
      results in a stable epigenetic conversion process, which can be performed
      recurrently--a phenomenon termed paramutation and discovered in Maize 60 y ago.
      Paramutation in Drosophila corresponds to the first stable paramutation in
      animals and provides a model system to investigate the epigenetically induced
      emergence of a piRNA-producing locus, a crucial step in epigenome shaping. In
      this Extra View, we discuss some additional functional aspects and the possible
      molecular mechanism of this piRNA-linked paramutation.

PMID- 24088601
TI  - Role of extracellular proton-sensing OGR1 in regulation of insulin secretion and
      pancreatic beta-cell functions.
AB  - Insulin secretion with respect to pH environments has been investigated for a
      long time but its mechanism remains largely unknown. Extracellular pH is usually
      maintained at around 7.4 and, its change has been thought to occur in non
      physiological situations. Acidification takes place under ischemic and
      inflammatory microenvironments, where stimulation of anaerobic glycolysis results
      in the production of lactic acid. In addition to ionotropic ion channels, such as
      transient receptor potential V1 (TRPV1) and acid-sensing ion channels (ASICs),
      metabotropic proton-sensing G protein-coupled receptors (GPCRs) have also been
      identified recently as proton-sensing machineries. While ionotropic ion channels
      usually sense strong acidic pH, proton-sensing GPCRs sense pH of 7.6 to 6.0 and
      have been shown to mediate a variety of biological actions in neutral and mildly
      acidic pH environments. Studies with receptor knockout mice have revealed that
      proton-sensing receptors, including ovarian cancer G protein-coupled receptor 1
      (OGR1), a proton-sensing GPCRs, play a role in the regulation of insulin
      secretion and glucose metabolism under physiological conditions. Small molecule
      3,5-disubstituted isoxazoles have recently been identified as OGR1 agonists
      working at neutral pH and have been shown to stimulate pancreatic beta-cell
      differentiation and insulin synthesis. Thus, proton-sensing OGR1 may be an
      important player for insulin secretion and a potential target for improving beta
      cell function. 

PMID- 24088603
TI  - Direct electrochemical DNA detection originated from the self-redox signal of
      sulfonated polyaniline enhanced by graphene oxide in neutral solution.
AB  - In this paper, a type of direct DNA impedance detection using the self-redox
      signal change of sulfonated polyaniline (SPAN) enhanced by graphene oxide (GNO)
      was reported, here SPAN is a copolymer obtained from aniline and m
      aminobenzenesulfonic acid. The resulting nanocomposite was characterized by
      scanning electron microscopy, transmission electron microscopy, Fourier transform
      infrared spectroscopy, cyclic voltammetry, and electrochemical impedance
      spectroscopy. The pi-pi planar structure of GNO and the carboxyl groups on the
      surface of GNO ensured it could act as an excellent substrate for adsorption and
      polymerization of aniline monomer. Because of the existence of GNO, the
      electrochemical activities of SPAN were enhanced obviously. Because of abundant
      sulfonic acid groups, the resulting nanocomposite showed obvious self-redox
      signal even at physiological pH, which is beneficial for biosensing field. DNA
      probes with amine groups could be covalently attached to the modified electrode
      surface through the acyl chloride cross-linking reaction of sulfonic groups and
      amines. When the flexible probe DNA was successfully grafted, the electrode was
      coated and electron transfer between electrode and buffer was restrained. Thus,
      the inner impedance value of SPAN (rather than using outer classic EIS probe,
      [Fe(CN)6](3-/4-)) increased significantly. After hybridization, the rigid helix
      opened the electron channel, which induced impedance value decreased
      dramatically. As an initial application of this system, the PML/RARA fusion gene
      sequence formed from promyelocytic leukemia (PML) and retinoic acid receptor
      alpha (RARA) was successfully detected. 

PMID- 24088604
TI  - The development of the metabolic syndrome and insulin resistance after adjuvant
      treatment for breast cancer.
AB  - BACKGROUND: Adjuvant breast cancer treatment is associated with a number of
      adverse physical changes, including weight gain, and therefore may represent a
      critical period for the development of metabolic disturbance. OBJECTIVE: The aim
      of this study was to evaluate changes in the presentation of the metabolic
      syndrome (MetSyn) and insulin resistance from breast cancer surgery to
      postcompletion of adjuvant treatment. METHODS: Sixty-one participants who had
      completed metabolic screening, including fasting blood samples and anthropometric
      measurements, on the morning of breast cancer surgery were recruited. Measures
      were repeated after completion of adjuvant treatment. Change in the proportion of
      participants presenting with the MetSyn was evaluated using the related-samples
      McNemar test, and changes in measures of glucose metabolism (fasting insulin,
      insulin resistance [homeostatic model assessment index], and glycosylated
      hemoglobin [HbA1c]) were analyzed using paired t tests. The Kruskal-Wallis test
      was used to compare differences in changes in metabolic parameters across
      clinical and lifestyle characteristics. RESULTS: There was a significant (P <
      .001) increase in fasting insulin (mean [SE] change, 2.73 [0.57] mU/L),
      homeostatic model assessment index (0.58 [0.14]), and HbA1c level (4.49 [5.63]
      mmol/mol) from baseline to follow-up along with an increase in the proportion
      diagnosed with the MetSyn (P = .03). Those with the MetSyn at diagnosis
      experienced a greater increase in insulin resistance. Premenopausal women
      experienced greatest increases in HbA1c level. CONCLUSIONS: Results demonstrate
      the development of significant metabolic dysfunction, characterized by glucose
      dysmetabolism and MetSyn, after adjuvant treatment for breast cancer.
      IMPLICATIONS FOR PRACTICE: Interventions to improve the metabolic profile of
      breast cancer survivors are warranted.

PMID- 24088602
TI  - Functional role(s) of phagosomal Rab GTPases.
AB  - Rab GTPases are at the central node of the machinery that regulates trafficking
      of organelles, including phagosomes. Thanks to the unique combination of high
      quality phagosome purification with highly sensitive proteomic studies, the
      network of Rab proteins that are dynamically associated with phagosomes during
      the process of maturation of this organelle is relatively well known. Whereas the
      phagosomal functions of many of the Rab proteins associated with phagosomes are
      characterized, the role(s) of most of these trafficking regulators remains to be
      identified. In some cases, even when the function in the context of phagosome
      biology is described, phagosomal Rab proteins seem to have similar roles. This
      review summarizes the current knowledge about the identity and function of
      phagosomal Rab GTPases, with a particular emphasis on new evidence that clarify
      these seemingly overlapping Rab functions during phagosome maturation. 

PMID- 24088605
TI  - Aneuploidy in neuroblastoma tumors is not associated with inactivating point
      mutations in the STAG2 gene.
AB  - BACKGROUND: Chromosomal instability is a hallmark of human cancer caused by
      errors in mitotic control and chromosome segregation. STAG2 encodes a subunit of
      the cohesion complex that participates in mitotic chromatid separation and was
      recently found to show low expression and inactivating mutations in Ewing's
      sarcoma, melanoma and glioblastoma.In the childhood tumor neuroblastoma (NB)
      segmental chromosomal alterations are associated with poor prognosis whereas
      tumors displaying whole chromosome gains and losses have a much better prognosis.
      METHOD: As the genetic contribution to aneuploidy is unknown in NB, we
      investigated the presence of STAG2 mutations through sequence analysis of all 33
      coding exons in 37 primary NB tumors. RESULTS AND CONCLUSION: As no STAG2
      mutation was detected in this study, we conclude that inactivating mutation of
      STAG2 is not likely causative to neuroblastoma aneuploidy.

PMID- 24088606
TI  - On the formulation of the image reconstruction problem in magnetic particle
      imaging.
AB  - In magnetic particle imaging (MPI), the spatial distribution of magnetic
      nanoparticles is determined by applying various static and dynamic magnetic
      fields. Due to the complex physical behavior of the nanoparticles, it is
      challenging to determine the MPI system matrix in practice. Since the first
      publication on MPI in 2005, different methods that rely on measurements or
      simulations for the determination of the MPI system matrix have been proposed.
      Some methods restrict the simulation to an idealized model to speed up data
      reconstruction by exploiting the structure of an idealized MPI system matrix.
      Recently, a method that processes the measurement data in x-space rather than
      frequency space has been proposed. In this work, we compare the different
      approaches for image reconstruction in MPI and show that the x-space and the
      frequency space reconstruction techniques are equivalent.

PMID- 24088607
TI  - Recent examples on the clinical relevance of the CYP2D6 polymorphism and
      endogenous functionality of CYP2D6.
AB  - The cytochrome P450 2D6 (CYP2D6) belongs to a group of CYPs considered of utmost
      importance in the metabolism of xenobiotics. Despite being of only minor
      abundance in the liver, it is involved in the clearance of >25% of marketed
      drugs. Accordingly, CYP2D6 can be very efficiently inhibited by a couple of
      commonly used drugs such as some antidepressants, although induction by any drug
      has not been observed thus far. CYP2D6 was also one of the first enzymes for
      which a highly polymorphic expression could be shown leading to a widespread
      range of functionality, from a complete lack of a functional enzyme to
      overexpression due to multiplication of active alleles. A clear relationship
      between the CYP2D6 genotype and adverse events during treatment with CNS-active
      drugs such as codeine, antidepressants, or antipsychotics could be demonstrated.
      More recently, some new aspects emerged about the potential endogenous function
      of CYP2D6 in terms of behavior and brain disorders.

PMID- 24088608
TI  - The order of draw, myth or science.

PMID- 24088609
TI  - A short story on how the H-index may change the fate of scientists and scientific
      publishing.

PMID- 24088610
TI  - A specific and sensitive activated partial thromboplastin time (APTT)-based
      factor VIII inhibitor screening assay.

PMID- 24088611
TI  - The concentration of high-sensitivity troponin I, galectin-3 and NT-proBNP
      substantially increase after a 60-km ultramarathon.
AB  - BACKGROUND: The leading mechanisms responsible for the most prevalent and serious
      cardiac injuries include myocardiocyte stretch, myocardiocyte necrosis and
      cardiac fibrosis, which can now be reliably mirrored by measurement of
      natriuretic peptides, cardiospecific troponins and galectin-3, respectively.
      Although a large amount of knowledge has been gathered about the behavior and
      clinical significance of these biomarkers in patients with cardiac disorders,
      less information is available on their biology in paraphysiological conditions,
      including high-intensity endurance exercise. METHODS: The study population
      consisted of 18 trained athletes, who performed a 60-km ultramarathon run. Blood
      was collected before the run (i.e., "baseline") and immediately after the end of
      the ultramarathon ("post-marathon") for measurement of serum high-sensitivity
      troponin I (TnI), NT-proBNP and galectin-3. RESULTS: The concentration of all
      biomarkers measured in the post-marathon samples was remarkably increased as
      compared with the values obtained on baseline specimens. In particular, the
      median increase was 3.3 for TnI, 3.5 for NT-proBNP and 2.4 for galectin-3,
      respectively. The frequency of values exceeding the diagnostic threshold did not
      differ at baseline and after the ultramarathon for TnI (6% vs. 25%; p=0.15),
      instead was significantly increased for NT-proBNP (0% vs. 28%; p=0.016) and
      galectin-3 (0% vs. 67%; p<0.001). No significant correlation was found among the
      increase of any of the three biomarkers. CONCLUSIONS: The results of this study
      demonstrate that high-intensity endurance exercise is associated with biochemical
      abnormalities that may reflect adverse consequences on cardiac structure and
      biology.

PMID- 24088612
TI  - Haemoglobinopathies in nonendemic areas in recent years.

PMID- 24088613
TI  - Radioimmunoassay of free plasma metanephrines for the diagnosis of catecholamine
      producing tumors.
AB  - BACKGROUND: The determination of plasma metanephrines (MNs) provides a highly
      sensitive test for the diagnosis of catecholamine producing tumors.
      Chromatographic determinations with electrochemical or mass spectrometric
      detections are the methods of choice, but immunological assays have been
      developed. This study evaluated the clinical performances of a radioimmunoassay
      for free MNs in plasma. METHODS: MNs, normetanephrine (NMN) and metanephrine (MN)
      and catecholamines, norepinephrine (NE) and epinephrine (E) were determined in
      plasma and urine of 533 patients suspected of catecholamine producing tumor.
      Urinary and plasma catecholamines and urinary MNs were determined by HPLC using
      amperometric detection. Plasma MNs were purified by solid phase chromatography
      and quantified by a specific radioimmunoassay. RESULTS: Fifty-nine patients had
      tumors (13 paraganglioma and 46 pheochromocytoma) and the diagnosis was excluded
      in 474 patients. Receiver operator characteristic curves have identified optimal
      thresholds at 100 pg/mL for plasma NMN (sensitivity 96.6% and specificity 95.8%)
      and 70 pg/mL for plasma MN (sensitivity 61.0% and specificity 96.8%). These cut
      off values were lower than those suggested by the manufacturer (170 and 100
      pg/mL, respectively). The sensitivity of combined MNs was similar in plasma
      (100%) and urine (98%) but higher than that of urinary catecholamines (85%,
      p<0.001). The specificity of combined MNs in plasma (95%) was higher than urinary
      MNs (85%, p<0.001) and plasma catecholamines (75%, p<0.001). CONCLUSIONS: Plasma
      free and urinary-total MNs have a better discriminative power than catecholamines
      in the diagnosis of catecholamines producing tumors. Using these established cut
      offs, measurement of plasma-free MN by radioimmunoassay represents an effective
      alternative to chromatographic methods.

PMID- 24088614
TI  - Autoantibody prevalence with an improved immunoassay for detecting cardiac
      troponin-specific autoantibodies.
AB  - BACKGROUND: Cardiac troponin-specific autoantibodies (cTnAAb) can interfere with
      the measurement of cardiac troponin I (cTnI) by immunoassays used for the
      diagnosis of myocardial infarction (MI). Here, an improved version of a previous
      autoantibody assay was validated and used to evaluate the cTnAAb prevalence in a
      cohort of consecutive chest pain patients presenting to an emergency department.
      METHODS: Admission samples from 510 patients with suspected MI were analyzed in
      parallel with two sandwich-type cTnAAb assays based on different cTnI epitopes
      used to capture cardiac troponin-bound cTnAAbs. RESULTS: Sample-specific
      backgrounds were lower for the new assay than for the old assay (median 1225 vs.
      2693 counts, p<0.001). Net signals of cTnAAb-positive samples were higher for the
      new assay than for the old assay (median 5076 vs. 3921 counts, p<0.001). Of all
      patients, 9.2% were cTnAAb-positive for the new assay and 7.3% for the old assay
      (p=0.013). Previous cardiac problems were not associated with cTnAAb status and
      cTnAAb status did not correlate with the 12-month outcome. CONCLUSIONS: With our
      new and more sensitive autoantibody assay, approximately one out of ten patients
      who presented to the initial cardiac triage had detectable amounts of cTnAAbs in
      the circulation. Because these cTnAAbs can interfere with state-of-the-art cTnI
      assays, their high prevalence should be acknowledged by clinical chemists,
      physicians, and kit manufacturers.

PMID- 24088615
TI  - Analysis of antibody response (IgM, IgG, IgG3) to Chikungunya virus using panel
      of peptides derived from envelope protein for serodiagnosis.
AB  - BACKGROUND: Many epidemic outbreaks of Chikungunya fever (CHIKF) have been
      reported throughout the world including India after its reemergence in 2005. The
      immuno protective role of envelope proteins during Chikungunya virus (CHIKV)
      infection has been reported. With the aim of identifying the immunodominant
      epitopes within the envelope protein we investigated the detailed analysis of
      fine specificity of antibody response in different individuals during CHIKV
      infection. METHODS: The peptides corresponding to the full length of E1, E2 and
      E3 proteins of S27 strain of CHIKV were synthesized and their seroreactivity with
      CHIKV positive patients' sera collected from different epidemic regions of India
      was determined using indirect ELISA. RESULTS: The data analysis reveals many
      potent epitopes throughout the length of envelope E2 protein thus displaying it
      as the most promising antigen for diagnostic purpose. We found that the main IgG
      isotype response to envelope protein was predominantly of subclass IgG3.
      Interestingly, most of the epitopes were found to be conserved for detecting IgM,
      IgG and IgG3 antibody response. CONCLUSIONS: Peptides E2P3, E2P7, E2P16 and E2P17
      were revealed as the most immunodominant peptides that together can form the
      basis for designing an accurate, economical and easy to synthesize a peptide
      based immunodiagnostic for CHIKV. This study provides new and important insight
      into the humoral response generated by CHIKV S27 strain during the early phase of
      infection.

PMID- 24088616
TI  - Making vaccine refusal less of a free ride.
AB  - Herd immunity against vaccine-preventable diseases is a public good because it is
      both non-excludable (meaning that there is no way to exclude people from using
      it) and non-rivalrous (meaning that one person's use does not limit or restrict
      others' use). Like other public goods, such as lighthouses, street lights and
      national defense, herd immunity is vulnerable to the "free rider" problem. We
      discuss four conventional responses to the free rider problem (participation
      mandates, exclusion, incentives, and social norms) and highlight how a public
      good perspective can inform the design of interventions to increase vaccine
      acceptance. 

PMID- 24088617
TI  - Reduction of heart failure rehospitalization using a weight management education
      intervention.
AB  - BACKGROUND: Previous investigators have demonstrated that patient adherence to
      optimal weight monitoring resulted in fewer heart failure (HF)-related
      rehospitalizations. OBJECTIVE: The aim of this study was to determine whether a
      weight management (WM) intervention can improve patients' WM ability and cardiac
      function and reduce HF-related rehospitalizations. METHODS: Heart failure
      patients were randomly assigned to an intervention group (n = 32) or a control
      group (n = 34). The intervention group received the WM intervention, including
      education about regular daily weight monitoring and coping skills when detecting
      sudden weight gain, with a WM booklet and scheduled telephone visits. Patients'
      WM ability was measured by the Weight Management Questionnaire (WMQ). We compared
      scores on the WMQ, New York Heart Association (NYHA) classification, and HF
      related rehospitalizations between the 2 groups at enrollment and at 6 months. We
      also analyzed the association of adherence to weight monitoring and
      rehospitalization in the intervention group during the 6-month follow-up.
      RESULTS: There were no significant differences in weight monitoring adherence, WM
      ability, and NYHA classification between the 2 groups at baseline. At 6 months,
      scores on all 4 subscales of the WMQ significantly increased within the
      intervention group, and the WM-practice subscale significantly improved within
      the control group. Adherence to weight monitoring was significantly improved in
      the intervention group compared with the control group (81.25% vs 11.76%; P <
      .01). At 6 months, there was a significant improvement in NYHA class in the
      intervention group compared with the control group (P = .03). Rehospitalizations
      related to HF were also fewer in the intervention group (0.28 +/- 0.63 vs 0.79 +/
      1.18; P = .03) during the follow-up duration. In the intervention group, those
      who weighed themselves regularly reported less HF-related rehospitalizations than
      did those who did not (0.23 +/- 0.43 vs 0.50 +/- 1.23; P = .62). CONCLUSION: This
      study demonstrates that the WM intervention had a positive impact on patients'
      adherence to weight monitoring, WM ability, and NYHA classification and reduced
      HF-related rehospitalization.

PMID- 24088618
TI  - Comparison of coping strategy and disease knowledge in dyads of parents and their
      adolescent with congenital heart disease.
AB  - BACKGROUND: Adolescents with congenital heart disease adopt their illness as a
      part of their lives using their own knowledge and coping strategies. Those who
      use task-oriented coping strategies, such as relying on education to obtain
      sufficient disease-related knowledge, demonstrate much higher resilience.
      However, most health providers tend to provide information about congenital heart
      disease mainly to the parents instead of the child, and many parents tend to be
      uncomfortable talking about the disease with their child. OBJECTIVES: The purpose
      of this study was to evaluate and compare adolescent patients' and their parents'
      coping strategies and knowledge of congenital heart disease. METHODS: A
      descriptive and exploratory study design was used. After approval of the
      institutional review board was obtained, 40 adolescents with congenital heart
      disease and their parents were recruited from a congenital heart clinic between
      October 2012 and February 2013. We assessed the coping strategies and disease
      related knowledge of both the adolescent patients and their parents. RESULTS: The
      knowledge level of adolescent patients and their parents had significant gaps
      between categories, and parents presented with significantly higher knowledge
      than their adolescents did (P < .01). Parents reported significantly higher mean
      scores on task-oriented and emotion-oriented coping than their adolescents did (P
      < .001). In addition, both adolescents and parents of a religious background
      reported significantly higher scores on emotion-oriented coping than did those
      who did not report a religion (P < .05). CONCLUSION: It is essential for
      healthcare providers to understand the ways in which adolescents and their
      parents cope with stress as well as the degree of their knowledge to better
      explicate the process of adaptation to the illness. Therefore, it is critical to
      develop effective structured and continuous intervention programs not only for
      adolescent patients and but also for their parents to enhance coping and
      knowledge of lifelong congenital heart disease.

PMID- 24088619
TI  - Meanings of people's lived experiences of surviving an out-of-hospital cardiac
      arrest, 1 month after the event.
AB  - BACKGROUND: The out-of-hospital cardiac arrest (OHCA) survival rate has been poor
      and stable for a long time, but more recent studies describe its increase.
      However, there are few studies in which people narrate their experiences from
      surviving. OBJECTIVE: The aim of this study was to elucidate meanings of people's
      lived experiences of surviving an OHCA with validated myocardial infarction (MI)
      etiology, 1 month after the event. METHODS: A purposive sample of 2 women and 9
      men was interviewed between February 2011 and May 2012. A phenomenological
      hermeneutical method was used for analysis, which involved 3 steps: naive reading
      and understanding, structural analysis, and comprehensive understanding. RESULTS:
      There were 2 themes, (1) returning to life and (2) revaluing life, and five
      subthemes, (1a) waking up and missing the whole picture, (1b) realizing it was
      not time to die, (2a) wondering why and seeking explanations, (2b) feeling
      ambiguous in relations, and (2c) wondering whether life will be the same. All
      were constructed from the analysis. CONCLUSIONS: Surviving an OHCA with validated
      MI etiology meant waking up and realizing that one had experienced a cardiac
      arrest and had been resuscitated. These survivors had memory loss and a need to
      know what had happened during the time they were dead/unconscious. They searched
      for a reason why they experienced an MI and cardiac arrest and had gone from
      being "heart-healthy" to having a lifelong illness. They all had the experience
      of passing from life to death and back to life again. For the participants, these
      differences led to a revaluation of what is important in life.

PMID- 24088620
TI  - Factors associated with delay in seeking care for acute decompensated heart
      failure.
AB  - BACKGROUND: Despite reports that persons with heart failure (HF) symptoms delay
      up to 7 days before seeking treatment, few studies have prospectively explored
      specific factors influencing treatment-seeking delay in this population.
      OBJECTIVE: The purpose of this study was to explore how factors related to the
      symptom experience, such as perception (number and intensity), evaluation
      (attribution and understanding), and response (behaviors of patients and others)
      influence delay in seeking treatment for symptoms of acute decompensated HF.
      METHODS: Patients hospitalized for acute HF were enrolled into an exploratory,
      descriptive study. Only those who had HF for 3 months or longer and a previous HF
      admission were eligible. Data on factors related to the symptom experience,
      response to symptoms, and delay time were collected by interview during
      hospitalization. Delay time measured in hours was analyzed using generalized
      linear modeling. RESULTS: The sample of 131 adults was predominately older (77 +/
      11.3 years) men (55.7%). The median delay time was 60 hours (2.5 days), with a
      range of 1 to 336 hours (14 days). Only 34 (25.9%) sought care in less than 12
      hours. Three variables were statistically significant determinants of long delay
      time-waiting to see if the symptoms would abate, receiving a passive response to
      symptoms from others, and living in a rural environment. These variables
      explained 13.9% of the variance in delay time. Clinical characteristics were not
      significant predictors of delay. CONCLUSIONS: The response of patients (wait-and
      see) and others (eg, don't worry) contributed to delay, as did living in a rural
      environment. Evaluative characteristics of attribution and understanding were not
      significant determinants of delay, suggesting that patient education alone will
      not effectively decrease delay. Instead, interventions directed toward decision
      making in response to symptoms and inclusion of family members in such
      discussions may be more effective.

PMID- 24088621
TI  - Development and validation of the Hypertension Self-care Profile: a practical
      tool to measure hypertension self-care.
AB  - BACKGROUND: Adequate self-care is crucial for blood pressure control. A number of
      hypertension (HBP) self-care instruments are available, but existing tools do not
      capture all the critical domains of HBP self-care and have limited evidence of
      reliability and validity. OBJECTIVE: The purpose of this study was to develop and
      validate a new tool--the HBP Self-Care Profile (HBP SCP)--in a sample of inner
      city residents. METHODS: The HBP SCP encompasses comprehensive domains of HBP
      self-care behaviors. Guided by 2 validated theoretical approaches--Orem's self
      care model and Motivational Interviewing--the HBP SCP includes 3 scales that can
      be used together or independently: Behavior, Motivation, and Self-efficacy. The
      sample included 213 English-speaking inner-city residents with HBP (mean age,
      68.6 years; 76.1% women; 81.7% African American). RESULTS: Item-total
      correlations ranged from 0.20 to 0.63 for Behavior, 0.46 to 0.70 for Motivation,
      and 0.40 to 0.74 for Self-efficacy, meeting the cutoff set a priori at 0.15.
      Internal consistency reliability coefficients ranged from 0.83 to 0.93.
      Concurrent and construct validities of the HBP SCP were achieved by significant
      correlations between HBP SCP scales and theoretically selected instruments (P <
      .05 for all correlation coefficients). The HBP SCP-Behavior scale also
      successfully discriminated between those with or without blood pressure control
      (P < .05). CONCLUSIONS: The reliability and validity of the HBP SCP were
      supported in this sample of inner-city residents with HBP. The high reliability
      estimates and strong evidence of validity should allow researchers to use the HBP
      SCP to assess and identify gaps in HBP self-care behavior, motivation, and self
      efficacy. Future research is warranted to evaluate the HBP SCP in diverse ethnic
      and age samples of hypertensive patient populations.

PMID- 24088622
TI  - The link of unintentional weight loss to cardiac event-free survival in patients
      with heart failure.
AB  - BACKGROUND: Patients with heart failure (HF) commonly have unintentional weight
      loss, depressive symptoms, and elevated levels of high-sensitivity C-reactive
      protein (hsCRP). Each of these variables has been independently associated with
      shorter cardiac event-free survival. However, little data exist on the
      relationships of unintentional weight loss, hsCRP level, and depressive symptoms
      to cardiac event-free survival. OBJECTIVE: The aims of this study were to
      determine (1) whether depressive symptoms and elevated hsCRP level predicted
      unintentional weight loss and (2) whether unintentional weight loss predicted
      shorter cardiac event-free survival. METHODS: This was a prospective study of 243
      consecutive HF patients (61% men, 61 +/- 14 years old) enrolled during an index
      hospitalization for HF exacerbation. Patients provided blood samples to measure
      hsCRP level and completed the Beck Depression Inventory to assess depressive
      symptoms at discharge. Body weight was measured at discharge and 6 months later.
      Unintentional weight loss was defined as weight loss of greater than 6% of body
      weight since discharge. Cardiac event-free survival was followed for 1 year after
      the second measurement of body weight through monthly telephone interviews.
      Hierarchical logistic regression was used to determine whether depressive
      symptoms and elevated hsCRP level predicted unintentional weight loss. Cox hazard
      regression was used to determine whether unintentional weight loss predicted
      cardiac event-free survival. RESULTS: Thirty-five patients (14.4%) experienced
      unintentional weight loss at 6 months after discharge. Hierarchical Cox hazard
      regression revealed that patients with unintentional weight loss had a 3.2 times
      higher risk for cardiac events, adjusting for other clinical factors (P < .001).
      In hierarchical logistic regression, elevated hsCRP level (odds ratio, 1.49; 95%
      confidence interval, 1.15-1.92) and depressive symptoms (odds ratio, 1.07, 95%
      confidence interval, 1.02-1.12) independently predicted unintentional weight
      loss. CONCLUSIONS: Unintentional weight loss was an independent predictor of poor
      outcomes. Heart failure patients with depressive symptoms and elevated hsCRP
      levels are at a higher risk for unintentional weight loss.

PMID- 24088623
TI  - Effects of internet addiction on heart rate variability in school-aged children.
AB  - BACKGROUND: The Internet has been gaining worldwide popularity in recent years,
      but a loss of control over Internet use might lead to negative impacts on our
      daily lives. OBJECTIVES: This study explored the effects of Internet addiction on
      autonomic nervous system function through heart rate variability (HRV) analysis.
      METHODS: This was a cross-sectional design. Data were collected from 240 school
      aged children who completed the Chinese Internet Addiction Scale and Pittsburgh
      Sleep Quality Index questionnaires. Spectral analysis was used to measure HRV.
      Independent t test was used to compare differences in characteristics and HRV
      between groups. A 2-way analysis of variance was used to examine group
      differences in HRV. RESULTS: Internet addicts had significantly lower high
      frequency (HF) percentage, logarithmically transformed HF, and logarithmically
      transformed total power and significantly higher low frequency percentage than
      did nonaddicts. Internet addicts who had insomnia had higher low frequency
      percentage and lower HF percentage, logarithmically transformed HF, and
      logarithmically transformed total power compared with nonaddicts who did not have
      insomnia. CONCLUSIONS: Internet addiction is associated with higher sympathetic
      activity and lower parasympathetic activity. The autonomic dysregulation
      associated with Internet addiction might partly result from insomnia, but the
      mechanism still needs to be further studied.

PMID- 24088624
TI  - The social structure of microbial community involved in colonization resistance.
AB  - It is well established that host-associated microbial communities can interfere
      with the colonization and establishment of microbes of foreign origins, a
      phenomenon often referred to as bacterial interference or colonization
      resistance. However, due to the complexity of the indigenous microbiota, it has
      been extremely difficult to elucidate the community colonization resistance
      mechanisms and identify the bacterial species involved. In a recent study, we
      have established an in vitro mice oral microbial community (O-mix) and
      demonstrated its colonization resistance against an Escherichia coli strain of
      mice gut origin. In this study, we further analyzed the community structure of
      the O-mix by using a dilution/regrowth approach and identified the bacterial
      species involved in colonization resistance against E. coli. Our results revealed
      that, within the O-mix there were three different types of bacterial species
      forming unique social structure. They act as 'Sensor', 'Mediator' and 'Killer',
      respectively, and have coordinated roles in initiating the antagonistic action
      and preventing the integration of E. coli. The functional role of each identified
      bacterial species was further confirmed by E. coli-specific responsiveness of the
      synthetic communities composed of different combination of the identified
      players. The study reveals for the first time the sophisticated structural and
      functional organization of a colonization resistance pathway within a microbial
      community. Furthermore, our results emphasize the importance of 'Facilitation' or
      positive interactions in the development of community-level functions, such as
      colonization resistance. 

PMID- 24088625
TI  - Coordinated transporter activity shapes high-affinity iron acquisition in
      cyanobacteria.
AB  - Iron bioavailability limits biological activity in many aquatic and terrestrial
      environments. Broad scale genomic meta-analyses indicated that within a single
      organism, multiple iron transporters may contribute to iron acquisition. Here, we
      present a functional characterization of a cyanobacterial iron transport pathway
      that utilizes concerted transporter activities. Cyanobacteria are significant
      contributors to global primary productivity with high iron demands. Certain
      cyanobacterial species employ a siderophore-mediated uptake strategy; however,
      many strains possess neither siderophore biosynthesis nor siderophore transport
      genes. The unicellular, planktonic, freshwater cyanobacterium, Synechocystis sp.
      PCC 6803, employs an alternative to siderophore-based uptake-reduction of Fe(III)
      species before transport through the plasma membrane. In this study, we combine
      short-term radioactive iron uptake and reduction assays with a range of
      disruption mutants to generate a working model for iron reduction and uptake in
      Synechocystis sp. PCC 6803. We found that the Fe(II) transporter, FeoB, is the
      major iron transporter in this organism. In addition, we uncovered a link between
      a respiratory terminal oxidase (Alternate Respiratory Terminal Oxidase) and iron
      reduction - suggesting a coupling between these two electron transfer reactions.
      Furthermore, quantitative RNA transcript analysis identified a function for
      subunits of the Fe(III) transporter, FutABC, in modulating reductive iron uptake.
      Collectively, our results provide a molecular basis for a tightly coordinated,
      high-affinity iron transport system. 

PMID- 24088626
TI  - Dispersal network structure and infection mechanism shape diversity in a
      coevolutionary bacteria-phage system.
AB  - Resource availability, dispersal and infection genetics all have the potential to
      fundamentally alter the coevolutionary dynamics of bacteria-bacteriophage
      interactions. However, it remains unclear how these factors synergise to shape
      diversity within bacterial populations. We used a combination of laboratory
      experiments and mathematical modeling to test how the structure of a dispersal
      network affects host phenotypic diversity in a coevolving bacteria-phage system
      in communities of differential resource input. Unidirectional dispersal of
      bacteria and phage from high to low resources consistently increased host
      diversity compared with a no dispersal regime. Bidirectional dispersal, on the
      other hand, led to a marked decrease in host diversity. Our mathematical model
      predicted these opposing outcomes when we incorporated modified gene-for-gene
      infection genetics. To further test how host diversity depended on the genetic
      underpinnings of the bacteria-phage interaction, we expanded our mathematical
      model to include different infection mechanisms. We found that the direction of
      dispersal had very little impact on bacterial diversity when the bacteria-phage
      interaction was mediated by matching alleles, gene-for-gene or related infection
      mechanisms. Our experimental and theoretical results demonstrate that the effects
      of dispersal on diversity in coevolving host-parasite systems depend on an
      intricate interplay of the structure of the underlying dispersal network and the
      specifics of the host-parasite interaction. 

PMID- 24088627
TI  - Purine biosynthesis-deficient Burkholderia mutants are incapable of symbiotic
      accommodation in the stinkbug.
AB  - The Riptortus-Burkholderia symbiotic system represents a promising experimental
      model to study the molecular mechanisms involved in insect-bacterium symbiosis
      due to the availability of genetically manipulated Burkholderia symbiont. Using
      transposon mutagenesis screening, we found a symbiosis-deficient mutant that was
      able to colonize the host insect but failed to induce normal development of
      host's symbiotic organ. The disrupted gene was identified as purL involved in
      purine biosynthesis. In vitro growth impairment of the purL mutant and its growth
      dependency on adenine and adenosine confirmed the functional disruption of the
      purine synthesis gene. The purL mutant also showed defects in biofilm formation,
      and this defect was not rescued by supplementation of purine derivatives. When
      inoculated to host insects, the purL mutant was initially able to colonize the
      symbiotic organ but failed to attain a normal infection density. The low level of
      infection density of the purL mutant attenuated the development of the host's
      symbiotic organ at early instar stages and reduced the host's fitness throughout
      the nymphal stages. Another symbiont mutant-deficient in a purine biosynthesis
      gene, purM, showed phenotypes similar to those of the purL mutant both in vitro
      and in vivo, confirming that the purL phenotypes are due to disrupted purine
      biosynthesis. These results demonstrate that the purine biosynthesis genes of the
      Burkholderia symbiont are critical for the successful accommodation of symbiont
      within the host, thereby facilitating the development of the host's symbiotic
      organ and enhancing the host's fitness values. 

PMID- 24088628
TI  - In and out: an analysis of epibiotic vs periplasmic bacterial predators.
AB  - Bdellovibrio and like organisms (BALO) are obligate predators of Gram-negative
      bacteria, belonging to the alpha- and delta-proteobacteria. BALO prey using
      either a periplasmic or an epibiotic predatory strategy, but the genetic
      background underlying these phenotypes is not known. Here we compare the
      epibiotic Bdellovibrio exovorus and Micavibrio aeruginosavorus to the periplasmic
      B. bacteriovorus and Bacteriovorax marinus. Electron microscopy showed that M.
      aeruginosavorus, but not B. exovorus, can attach to prey cells in a non-polar
      manner through its longitudinal side. Both these predators were resistant to a
      surprisingly high number of antibiotic compounds, possibly via 26 and 19
      antibiotic-resistance genes, respectively, most of them encoding efflux pumps.
      Comparative genomic analysis of all the BALOs revealed that epibiotic predators
      have a much smaller genome (ca. 2.5 Mbp) than the periplasmic predators (ca. 3.5
      Mbp). Additionally, periplasmic predators have, on average, 888 more proteins, at
      least 60% more peptidases, and one more rRNA operon. Fifteen and 219 protein
      families were specific to the epibiotic and the periplasmic predators,
      respectively, the latter clearly forming the core of the periplasmic 'predatome',
      which is upregulated during the growth phase. Metabolic deficiencies of epibiotic
      genomes include the synthesis of inosine, riboflavin, vitamin B6 and the
      siderophore aerobactin. The phylogeny of the epibiotic predators suggests that
      they evolved by convergent evolution, with M. aeruginosavorus originating from a
      non-predatory ancestor while B. exovorus evolved from periplasmic predators by
      gene loss. 

PMID- 24088629
TI  - Interaction of Pseudomonas aeruginosa Exotoxin A with the human Sec61 complex
      suppresses passive calcium efflux from the endoplasmic reticulum.
AB  - According to live-cell calcium-imaging experiments, the Sec61 complex is a
      passive calcium-leak channel in the human endoplasmic reticulum (ER) membrane
      that is regulated by ER luminal immunoglobulin heavy chain binding protein (BiP)
      and cytosolic Ca(2+)-calmodulin. In single channel measurements, the open Sec61
      complex is Ca(2+) permeable. It can be closed not only by interaction with BiP or
      Ca(2+)-calmodulin, but also with Pseudomonas aeruginosa Exotoxin A which can
      enter human cells by retrograde transport. Exotoxin A has been shown to interact
      with the Sec61 complex and, thereby, inhibit ER export of immunogenic peptides
      into the cytosol. Here, we show that Exotoxin A also inhibits passive Ca(2+)
      leakage from the ER in human cells, and we characterized the N-terminus of the
      Sec61 alpha-subunit as the relevant binding site for Exotoxin A.

PMID- 24088630
TI  - Bilateral extraocular muscles enlargement from Kimura's disease of the orbit.
AB  - Kimura's disease (KD) is a rare chronic inflammatory disease of unclear etiology,
      characterized by subcutaneous nodules, mainly in the head and neck region,
      frequently associated with regional lymphadenopathy. Orbital involvement is
      infrequent and when it occurs, usually affects the eyelid or the lacrimal gland.
      We report a case of a 44-year-old man that presented with bilateral slowly
      progressive proptosis that was initially misdiagnosed as Graves' Ophthalmopathy.
      15 months of worsening proptosis and the development of facial and temporal
      swelling led to further investigation. Computed tomography and magnetic resonance
      imaging showed enlargement of all recti muscles and diffuse orbital infiltration.
      An orbital biopsy was performed and was consistent with the diagnosis of KD. Long
      term oral corticosteroid showed marked improvement of proptosis and facial
      swelling. This case serves to emphasize that KD should be included in the
      differential diagnosis of inflammatory diseases of the orbit, even when
      characterized by predominant involvement of the extraocular muscles. 

PMID- 24088631
TI  - Tear function and ocular surface after Muller muscle-conjunctival resection.
AB  - Muller muscle-conjunctival resection (MCR) is a surgical technique to correct
      mild and moderate ptosis. In this study, tear function tests and ocular surface
      are evaluated in patients who underwent unilateral surgery. Sixteen patients with
      normal preoperative tear function who underwent unilateral MCR were evaluated
      prospectively. The fellow eyes of the patients were taken as the control group. A
      dry eye assessment questionnaire, Schirmer testing, tear film break-up time,
      fluorescein stain, Rose-Bengal stain, and conjunctival impression cytology were
      used to assess the tear film functions and ocular surface changes in the operated
      and non-operated eyes. There was no statistically significant difference in the
      tear function tests and goblet cell densities between the operated and non
      operated eyes. The results indicate that an MCR procedure has no apparent effect
      on tear function tests and goblet cell density in patients with normal
      preoperative tear function. 

PMID- 24088632
TI  - Combined endothelial keratoplasty and clear lens extraction for corneal
      decompensation in irido-corneal endothelial syndrome.
AB  - A 38-year-old woman presented with corneal decompensation in left eye secondary
      to irido-corneal endothelial (ICE) syndrome. She underwent simultaneous
      Descemet's stripping endothelial keratoplasty (DSEK) and clear lens extraction
      with posterior chamber intraocular lens implantation. The surgery was
      accomplished comfortably without rupture of peripheral anterior synechiae (PAS).
      5 weeks postoperatively, the graft was attached, the cornea was clear and best
      corrected visual acuity improved from 20/400 to 20/30. DSEK combined with clear
      lens extraction appears to be an effective measure to treat corneal
      decompensation in patients with ICE syndrome. Associated lens extraction in such
      cases increases the working space in anterior chamber for DSEK, which minimizes
      the intra-operative graft manipulation. This also avoids a future difficult
      cataract surgery in the presence of PAS and an endothelial graft, which may
      increase the chances of graft survival. 

PMID- 24088633
TI  - A rare case of subconjunctival dirofilariasis by Dirofilaria repens in rural
      Gujarat.
AB  - Dirofilariasis is a worldwide zoonotic filariasis with over 782 cases reported so
      far from different parts of the world. Human dirofilariasis, caused by
      Dirofilaria repens, have been reported to occur widely throughout Asia, Europe,
      and Africa. It has not been widely recognized in India, however; several cases
      have been reported in last few years. There is probably a focus of human
      infection with D. repens in Kerala. Herein, we present a review of human
      infections by D. repens, along with a case report of subconjunctival
      dirofilariasis from rural part of Gujarat. 

PMID- 24088634
TI  - Susac's syndrome: first from India and youngest in the world.
AB  - A two and half year old female was admitted at the emergency room suffering from
      gradually worsening headache followed by nausea. The child presented with reduced
      level of consciousness and bilateral hypoacusis. The patient was lethargic.
      Ophthalmic examination showed branch retinal artery occlusion (BRAO). This
      finding was crucial to the diagnosis of Susac's syndrome (SS), a rare autoimmune
      disease characterized by, endotheliopathy of retina, encephalic tissues and
      cochlea. Magnetic resonance imaging of the brain also showed typical features.
      Thorough blood investigations did not reveal any other abnormality. Patient was
      treated with immunosuppressive to prevent her from developing severe sequelae of
      this disease. The child showed dramatic improvement in her systemic condition
      within 48 h of starting the treatment. This is the youngest ever and first case
      report from India. 

PMID- 24088635
TI  - Minimally invasive strabismus surgery versus paralimbal approach: a randomized,
      parallel design study is minimally invasive strabismus surgery worth the effort?
AB  - INTRODUCTION: Minimal access surgery is common in all fields of medicine. We
      compared a new minimally invasive strabismus surgery (MISS) approach with a
      standard paralimbal strabismus surgery (SPSS) approach in terms of post-operative
      course. MATERIALS AND METHODS: This parallel design study was done on 28 eyes of
      14 patients, in which one eye was randomized to MISS and the other to SPSS. MISS
      was performed by giving two conjunctival incisions parallel to the horizontal
      rectus muscles; performing recession or resection below the conjunctival strip so
      obtained. We compared post-operative redness, congestion, chemosis, foreign body
      sensation (FBS), and drop intolerance (DI) on a graded scale of 0 to 3 on post
      operative day 1, at 2-3 weeks, and 6 weeks. In addition, all scores were added to
      obtain a total inflammatory score (TIS). STATISTICAL ANALYSIS: Inflammatory
      scores were analyzed using Wilcoxon's signed rank test. RESULTS: On the first
      post-operative day, only FBS (P = 0.01) and TIS (P = 0.04) showed significant
      difference favoring MISS. At 2-3 weeks, redness (P = 0.04), congestion (P =
      0.04), FBS (P = 0.02), and TIS (P = 0.04) were significantly less in MISS eye. At
      6 weeks, only redness (P = 0.04) and TIS (P = 0.05) were significantly less.
      CONCLUSION: MISS is more comfortable in the immediate post-operative period and
      provides better cosmesis in the intermediate period.

PMID- 24088636
TI  - Linezolid-induced optic neuropathy.
AB  - Many systemic antimicrobials have been implicated to cause ocular adverse
      effects. This is especially relevant in multidrug therapy where more than one
      drug can cause a similar ocular adverse effect. We describe a case of progressive
      loss of vision associated with linezolid therapy. A 45-year-old male patient who
      was on treatment with multiple second-line anti-tuberculous drugs including
      linezolid and ethambutol for extensively drug-resistant tuberculosis (XDR-TB)
      presented to us with painless progressive loss of vision in both eyes. Color
      vision was defective and fundus examination revealed optic disc edema in both
      eyes. Ethambutol-induced toxic optic neuropathy was suspected and tablet
      ethambutol was withdrawn. Deterioration of vision occurred despite withdrawal of
      ethambutol. Discontinuation of linezolid resulted in marked improvement of
      vision. Our report emphasizes the need for monitoring of visual function in
      patients on long-term linezolid treatment. 

PMID- 24088637
TI  - Corneal arcus and xanthomas in homozygous familial hypercholesterolemia: first
      report from China.
AB  - We report the case of a 12-year-old male who developed corneal arcus and multiple
      skin lesions with a 10-year history of xanthomas. The lesions appeared over his
      fingers, hands, elbows, knees, buttocks and feet. Laboratory studies showed a
      total serum cholesterol level of 752.1 mg/dL; a triglyceride level of 96.6 mg/dL;
      a low-density lipoprotein cholesterol level of 661.3 mg/dL. Findings were
      consistent with homozygous familial hypercholesterolemia. To our knowledge, this
      is the first such case to be reported from China. 

PMID- 24088638
TI  - Query to the author of "Spectacle compliance amongst rural secondary school
      children in Pune district, India".

PMID- 24088639
TI  - Enhanced visualization of acute macular neuroretinopathy by infrared imaging and
      spectral optical coherence tomography.

PMID- 24088641
TI  - Multifocal visual evoked potential in optic neuritis, ischemic optic neuropathy
      and compressive optic neuropathy.
AB  - PURPOSE: To investigate the effect of optic neuritis (ON), ischemic optic
      neuropathy (ION) and compressive optic neuropathy (CON) on multifocal visual
      evoked potential (mfVEP) amplitudes and latencies, and to compare the parameters
      among three optic nerve disorders. MATERIALS AND METHODS: mfVEP was recorded for
      71 eyes of controls and 48 eyes of optic nerve disorders with subgroups of optic
      neuritis (ON, n = 21 eyes), ischemic optic neuropathy (ION, n = 14 eyes), and
      compressive optic neuropathy (CON, n = 13 eyes). The size of defect in mfVEP
      amplitude probability plots and relative latency plots were analyzed. The pattern
      of the defect in amplitude probability plot was classified according to the
      visual field profile of optic neuritis treatment trail (ONTT). RESULTS: Median of
      mfVEP amplitude (log SNR) averaged across 60 sectors were reduced in ON (0.17
      (0.13-0.33)), ION (0.14 (0.12-0.21)) and CON (0.21 (0.14-0.30)) when compared to
      controls. The median mfVEP relative latencies compared to controls were
      significantly prolonged in ON and CON group of 10.53 (2.62-15.50) ms and 5.73
      (2.67-14.14) ms respectively compared to ION group (2.06 (-4.09-13.02)). The
      common mfVEP amplitude defects observed in probability plots were diffuse pattern
      in ON, inferior altitudinal defect in ION and temporal hemianopia in CON eyes.
      CONCLUSIONS: Optic nerve disorders cause reduction in mfVEP amplitudes. The
      extent of delayed latency noted in ischemic optic neuropathy was significantly
      lesser compared to subjects with optic neuritis and compressive optic neuropathy.
      mfVEP amplitudes can be used to objectively assess the topography of the visual
      field defect.

PMID- 24088642
TI  - Association of extensive myelinated nerve fibers and high degree myopia: case
      report.
AB  - Unilateral extensive myelination of the peripapillary nerve fibers may be
      associated with anisometropic myopia, strabismus, and reduced vision. Myelination
      of optic nerve fibers terminate at lamina cribrosa. Yet in some patients,
      myelination progresses into the peripapillary retinal nerve fibers and may affect
      the visual acuity. In this report, we described 4 patients. All patients
      presented extensive peripapillary myelinated nerve fibers associated with myopic
      anisometropia. After routine ophthalmic and orthoptic examinations, all patients
      underwent treatment for amblyopia through correction with spectacles, contact
      lenses, and the occlusion of the good eye. Corrected visual acuity improved in 1
      patient, but 3 patients had no increase in visual acuity despite treatment with
      full cycloplegic refraction and appropriate patching. Probably because of
      structural abnormalies of the macula, visual results are often disappointing with
      appropriate correction of the refractive error and occlusion. 

PMID- 24088643
TI  - Impact of the day-30 screening strategy on the disease presentation and outcome
      of retinopathy of prematurity. The Indian twin cities retinopathy of prematurity
      report number 3.
AB  - CONTEXT: Outcomes of various screening strategies in retinopathy of prematurity
      are not well reported. AIM: To assess the impact of a city-wide, ROP screening
      strategy, on the disease presentation and treatment outcome. MATERIALS AND
      METHODS: A retrospective case-control study from a prospectively collected ROP
      data-base was analyzed. Cases (group 1a) included ROP babies that were screened
      directly in neonatal intensive care units, and controls (group 1b) were babies
      referred directly to the institute from other neonatal centers during the same
      period. Historical controls (group 2) were ROP cases seen in the years preceding
      establishment of this ROP program and database. Primary outcome measure was the
      risk of eyes presenting with stage 4 or worse ROP, and main secondary outcome
      measure was the final anatomic outcome. RESULTS: Of the 643 cases screened, 322
      eyes of 161 babies had ROP. The median age of 7.19 months at presentation for the
      46 patients (92 eyes) in group 2 was higher than the median age of 1.29 months
      for the 115 patients (230 eyes) in group 1. Within the group 1, group 1a had
      lower median age at presentation than group 1b (0.91 months versus 2.30 months).
      The relative risk of an eye presenting in the stage 4 and 5 in group 2 was 4.7
      times higher (95% confidence interval 3.07 -7.32) than in group 1. Eyes that
      could be given treatment in group 2 were significantly less (P < 0.0005) than in
      group 1. The relative risk of poor outcome in group 2 was 3.83 times higher (95%
      confidence interval 2.75 -5.34) than in group 1. Group 1a eyes had the best
      outcomes. CONCLUSION: Early screening before one month of age in neonatal centers
      detects the disease early where prompt treatment can lead to favorable outcomes.
      The study provides early results of a model strategy for ROP screening.

PMID- 24088644
TI  - In vitro cytocidal effects of the essential oil from Croton cajucara (red sacaca)
      and its major constituent 7- hydroxycalamenene against Leishmania chagasi.
AB  - BACKGROUND: Visceral leishmaniasis is the most serious form of leishmaniasis and
      can be lethal if left untreated. Currently available treatments for these
      parasitic diseases are frequently associated to severe side effects. The leaves
      of Croton cajucara are used as an infusion in popular medicine to combat several
      diseases. Previous studies have demonstrated that the linalool-rich essential oil
      from C. cajucara (white sacaca) is extremely efficient against the tegumentary
      specie Leishmania amazonensis. In this study, we investigated the effects of the
      7-hydroxycalamenene-rich essential oil from the leaves of C. cajucara (red
      sacaca) against Leishmania chagasi, as well as on the interaction of these
      parasites with host cells. METHODS: Promastigotes were treated with different
      concentrations of the essential oil for determination of its minimum inhibitory
      concentration (MIC). In addition, the effects of the essential oil on parasite
      ultrastructure were analyzed by transmission electron microscopy. To evaluate its
      efficacy against infected cells, mouse peritoneal macrophages infected with L.
      chagasi promastigotes were treated with the inhibitory and sub-inhibitory
      concentrations of the essential oil. RESULTS: The minimum inhibitory
      concentrations of the essential oil and its purified component 7
      hydroxycalamenene against L. chagasi were 250 and 15.6 MUg/mL, respectively.
      Transmission electron microscopy analysis revealed important nuclear and
      kinetoplastic alterations in L. chagasi promastigotes. Pre-treatment of
      macrophages and parasites with the essential oil reduced parasite/macrophage
      interaction by 52.8%, while it increased the production of nitric oxide by L.
      chagasi-infected macrophages by 80%. CONCLUSION: These results indicate that the
      7-hydroxycalamenene-rich essential oil from C. cajucara is a promising source of
      leishmanicidal compounds.

PMID- 24088645
TI  - What the newspapers say about medication adherence: a content analysis.
AB  - BACKGROUND: This study investigates the coverage of adherence to medicine by the
      UK and US newsprint media. Adherence to medicine is recognised as an important
      issue facing healthcare professionals and the newsprint media is a key source of
      health information, however, little is known about newspaper coverage of
      medication adherence. METHODS: A search of the newspaper database Nexis(r)UK from
      2004-2011 was performed. Content analysis of newspaper articles which referenced
      medication adherence from the twelve highest circulating UK and US daily
      newspapers and their Sunday equivalents was carried out. A second researcher
      coded a 15% sample of newspaper articles to establish the inter-rater reliability
      of coding. RESULTS: Searches of newspaper coverage of medication adherence in the
      UK and US yielded 181 relevant articles for each country. There was a large
      increase in the number of scientific articles on medication adherence in
      PubMed(r) over the study period, however, this was not reflected in the frequency
      of newspaper articles published on medication adherence. UK newspaper articles
      were significantly more likely to report the benefits of adherence (p = 0.005),
      whereas US newspaper articles were significantly more likely to report adherence
      issues in the elderly population (p = 0.004) and adherence associated with
      diseases of the central nervous system (p = 0.046). The most commonly reported
      barriers to adherence were patient factors e.g. poor memory, beliefs and age,
      whereas, the most commonly reported facilitators to adherence were medication
      factors including simplified regimens, shorter treatment duration and combination
      tablets. HIV/AIDS was the single most frequently cited disease (reported in 20%
      of newspaper articles). Poor quality reporting of medication adherence was
      identified in 62% of newspaper articles. CONCLUSION: Adherence is not well
      covered in the newspaper media despite a significant presence in the medical
      literature. The mass media have the potential to help educate and shape the
      public's knowledge regarding the importance of medication adherence; this
      potential is not being realised at present.

PMID- 24088646
TI  - Antiplatelet effects of caffeic acid due to Ca(2+) mobilizationinhibition via
      cAMP-dependent inositol-1, 4, 5-trisphosphate receptor phosphorylation.
AB  - AIM: In this study, we investigated the effects of caffeic acid (CAFA), a
      phenolic acid, on Ca(2+)-antagonistic cyclic nucleotides associated with the
      phosphorylation of inositol 1,4,5-trisphosphate receptor (IP3R) and vasodilator
      stimulated phosphoprotein (VASP) and the thromboxane A2 (TXA2)-associated
      microsomal cyclooxygenase-1 (COX-1) activity in collagen (10 MUg/mL)-stimulated
      platelet aggregation. METHODS: Washed platelets (10(8)/mL) obtained from Sprague
      Dawley rats (6-7 weeks old, male) were preincubated for 3 minutes at 37C in the
      presence of 2 mM exogenous CaCl2 with or without CAFA or other materials,
      stimulated with collagen (10 MUg/mL) for 5 minutes, then used to determine the
      levels of intracellular cytosolic Ca(2+) ([Ca(2+)]i), TXA2, cyclic adenosine
      monophosphate (cAMP), cyclic guanosine monophosphate (cGMP), COX-1 activity, VASP
      and IP3R phosphorylation. RESULTS: CAFA dose-dependently inhibited collagen
      induced platelet aggregation and suppressed the production of TXA2, an
      aggregation-inducing autacoid associated with the strong inhibition of COX-1 in
      platelet microsomes exhibiting cytochrome C reductase activity. CAFA dose
      dependently inhibited collagen-elevated [Ca(2+)]i mobilization, which was
      increased by a cAMP-dependent protein kinase (A-kinase) inhibitor, Rp-8-Br-cAMPS,
      but not a cGMP-dependent protein kinase (G-kinase) inhibitor, Rp-8-Br-cGMPS. In
      addition, CAFA significantly increased the formation of cAMP and cGMP,
      intracellular Ca(2+)-antagonists that function as aggregation-inhibiting
      molecules. CAFA increased IP3R (320 kDa) phosphorylation, indicating the
      inhibition of IP3-mediated Ca(2+) release from internal stores (i.e. the dense
      tubular system) via the IP3R on collagen-activated platelets. Furthermore, CAFA
      induced IP3R phosphorylation was strongly inhibited by an A-kinase inhibitor, Rp
      8-Br-cAMPS, but only mildly inhibited by a G-kinase inhibitor, Rp-8-Br-cGMPS.
      These results suggest that the inhibition of [Ca(2+)]i mobilization by CAFA is
      resulted from the cAMP/A-kinase-dependent phosphorylation of IP3R. CAFA elevated
      the phosphorylation of VASP-Ser(157), an A-kinase substrate, but not the
      phosphorylation of VASP-Ser(239), a G-kinase substrate. We demonstrate that CAFA
      increases cAMP and subsequently phosphorylates both IP3R and VASP-Ser(157)
      through A-kinase activation to inhibit [Ca(2+)]i mobilization and TXA2 production
      via the inhibition of the COX-1 activity. CONCLUSIONS: These results strongly
      indicate that CAFA is a potent beneficial compound that elevates the level of
      cAMP-dependent protein phosphorylation in collagen-platelet interactions, which
      may result in the prevention of platelet aggregation-mediated thrombotic
      diseases.

PMID- 24088647
TI  - Esophageal schwannoma: a case report.
AB  - Most tumorous lesions of the esophagus are esophageal cancers. Benign primary
      tumors of the esophagus are uncommon, and account for approximately 2% of all
      esophageal tumors. More than 80% of benign esophageal tumors are leiomyomas, with
      schwannomas being rare. A 55-year-old woman visited our internal medicine
      department with complaints of palpitations and discomfort during swallowing. A
      chest computed tomography scan showed a lobulated tumor (75 * 57 * 80 mm) in the
      upper to middle mediastinum, with homogenous inner opacity, compressing the
      esophagus. Upper gastrointestinal endoscopy revealed a smooth-surfaced elevated
      lesion covered with normal mucosa, and a schwannoma was diagnosed based on the
      biopsy result. The tumor was large. It was thus considered to be difficult to
      repair the esophagus by direct anastomosis after tumor resection. Therefore,
      subtotal esophagectomy and esophagogastrostomy in the right thorax were
      performed. Histopathological examination revealed spindle-shaped cells in a
      fasciculated and disarrayed architecture and nuclei in a palisading pattern.
      Immunohistochemical studies revealed S100 protein positivity and the absence of
      staining for alpha smooth muscle actin (alphaSMA), CD34 and CD117, thereby
      establishing the diagnosis of benign schwannoma. Her postoperative course was
      uneventful and there has been no evidence of recurrence to date. 

PMID- 24088648
TI  - [The methodological silence?--A look at the research landscape of mixed method
      studies].

PMID- 24088649
TI  - [Hospital discharge preparation: enhancing self-care competence of patients after
      minimally invasive hip arthroplasty].
AB  - Increasing numbers of hip replacement implant surgeries in Switzerland today are
      minimally invasive. Patients undergoing such procedures become mobile faster and
      are discharged from hospital to home within an average of four days. Using a
      qualitative descriptive design, this study examined how post-operative self-care
      is taught to patients in the orthopaedic department of a rehabilitation hospital
      after a minimally invasive hip arthroplasty and explored ways to optimise such
      teaching methods. Data were collected by conducting three focus groups with nine
      nursing professionals and expert interviews with the chief surgeon and the
      assigned physiotherapist. Data were analysed by using qualitative content
      analysis procedures. Results showed that teaching to enhance self-care competence
      of patients was not carried out systematically. Instead, the primary focus was to
      inform and prescribe rather than empower patients. Empowerment, however, would be
      necessary to assure adherence to the treatment regime. Hospital discharge often
      takes place surprisingly early and prevents assessment-based counselling of
      patients. The researchers concluded that the introduction of the minimally
      invasive surgical technique requires that the multidisciplinary rehabilitation
      team adapts its teaching methods. Self-care confidence in patients should be
      enhanced by following participatory clinical pathways. This demands modification
      in discharge and rehabilitation teaching plans to make them patient-oriented, and
      the plans should be supported by the entire team and the management. 

PMID- 24088650
TI  - ["It's not the old life that we live anymore..."--counselling of relatives in
      nurse discharge planning].
AB  - In Germany, discharge planning has been a mandatory part of hospital care since
      2012 to ensure continuity of care and to support patients and relatives while
      crossing the critical interface between hospital and home care. However, it
      remains unclear how the information and counselling of informal caregivers
      integrated into this process can be conceptualised. An explorative study using
      focus groups was carried out aiming at identifying the carers' views and
      experiences for a needs-based conceptualisation of the information and
      counselling in discharge planning. The results indicate when, according to the
      interviewees, information and counselling should be offered and the importance of
      trust within the consultation process which should reach beyond the hospital
      setting. In addition to illness- and care-related aspects as well as
      organisational and administrative issues, carers also expressed needs for support
      in emotional coping, problem solving, relief of burden and peer support in
      everyday life. Integrating carers in the conceptualisation of discharge planning
      will help to develop needs-based information and counselling services. 

PMID- 24088651
TI  - [Nurses' experiences with aggressive behaviour of nursing home residents: a cross
      sectional study in Swiss nursing homes].
AB  - The present exploratory descriptive cross-sectional study with the participation
      of 814 (51.8%) caregivers in 21 Swiss nursing homes provides insight into
      caregivers' experiences and handling of residents' aggressive behaviour.
      Moreover, caregiver burden with regard to resident aggression and the
      consequences on the caregiver-resident-relationship were investigated. The survey
      was carried out by means of validated questionnaire. Approximately 38% of
      participants experienced aggressive incidents during the last seven days prior to
      data collection. In most cases aggressive behaviour was caused by residents
      suffering from dementia and/or depression and occurred during nursing
      interventions involving physical contact. As a trigger for aggressive behaviour
      participants predominately assumed "non-understanding and excessive demand" of
      residents. Reassuring conversation and keeping oneself at a distance were most
      often used to calm the situation. Approximately 40% of participants experienced
      physical attacks as especially distressing and circa 23% were frightened,
      particularly when aggressive behaviour occurred without warning. Approximately 4%
      of caregivers avoided contact with residents after an aggressive incident and
      12.3% perceived a disturbed relationship. It can be assumed that caregivers do
      not adequately perceive emotions possibly underlying aggressive behaviour in the
      escalation phase and therefore may not identify early signs of beginning
      aggression.

PMID- 24088652
TI  - [Development, application and evaluation of nursing interventions for people with
      dementia in nursing homes in Germany--a literature review].
AB  - In 2007 guidelines for the care of people with dementia living in nursing homes,
      especially for handling challenging behaviour, have been published that recommend
      certain interventions. The aim of this study is a systematic review of
      publications about projects and the development and utilisation of interventions
      recommended in the German guideline in German nursing homes. For this purpose, 22
      publications from 8 projects were analysed. The analysis was carried out on the
      basis of the CReDECI-criteria for the reporting of complex interventions. The
      publications described the application of reminiscence-therapy, Snoezelen,
      Dementia Care Mapping (DCM) and the use of understanding diagnostics as well as
      assessment instruments. Although the interventions were based on similar
      theoretical frames and had the same aim they contained different components. For
      the implementation a considerably amount of teaching and support by the project
      members was needed. A process evaluation as well as information about necessary
      adaptations to general conditions was given seldom. Partly, information that is
      important for the use in practice as well as in continuative studies is missing
      in the publications. 

PMID- 24088653
TI  - [Implementation of primary nursing in intensive care settings--evaluation with
      the "Instrument zur Erfassung von Pflegesystemen" (IzEP(c))].

PMID- 24088654
TI  - [Unfair peer review process?].

PMID- 24088662
TI  - Expression of gonadotropin-inhibitory hormone receptors in mouse pituitary
      gonadotroph LbetaT2 cells and hypothalamic gonadotropin-releasing hormone
      producing GT1-7 cells.
AB  - Gonadotropin-inhibitory hormone (GnIH) was first identified in quail as a novel
      neurohormone that acts directly on the anterior pituitary to inhibit gonadotropin
      release. GnIH inhibits not only gonadotropin release from the pituitary gland but
      also inhibits the release of gonadotropin-releasing hormone (GnRH) from the
      hypothalamus. In this study, we examined how GnIH receptors were regulated in
      pituitary gonadotroph cells and GnRH-producing neurons in the hypothalamus. In
      the mouse pituitary gonadotroph cell line LbetaT2, GnRH increased expression of
      the GnIH receptor, G-protein coupled receptor 74 (GPR74). GnRH also stimulated
      the expression of GPR74 and GPR147 in primary cultures of rat anterior pituitary
      cells. In addition, when GnRH was administered to LbetaT2 cells in a pulsatile
      manner, low frequency GnRH pulse stimulation stimulated GPR74 and GPR147
      expression more than did high frequency GnRH pulses. In the mouse hypothalamic
      GnRH-producing cell line GT1-7, hypothalamic kisspeptin did not significantly
      increase the expression of GnIH receptors. However, the intermittent
      administration of kisspeptin to GT1-7 cells significantly increased GPR74 and
      GPR147 mRNA expression. The overexpression of either constitutively active MEK
      kinase (MEKK) or protein kinase A (PKA) in LbetaT2 cells increased the expression
      of GPR74 mRNA. Conversely, in GT1-7 cells, although the overexpression of either
      MEKK or PKA failed to stimulate GnIH receptor expression, the combined
      overexpression of both kinases together increased GPR74 and GPR147 mRNA levels.
      Our current observations suggest that two central controllers of reproductive
      function, GnRH and kisspeptin, stimulate the expression of GnIH receptors in
      pituitary gonadotroph cells and hypothalamic GnRH neurons. 

PMID- 24088663
TI  - Critical role of Yp inversion in PRKX/PRKY-mediated Xp;Yp translocation in a
      patient with 45,X testicular disorder of sex development.
AB  - 45,X testicular disorder of sex development (TDSD), previously known as 45,X
      maleness, with unbalanced Xp;Yp translocation is an extremely rare condition
      caused by concomitant occurrence of loss of an X chromosome of maternal origin
      and an aberrant Xp;Yp translocation during paternal meiosis. We identified a
      Japanese male infant with an apparently 45,X karyotype who exhibited
      chondrodysplasia punctata and growth failure. Cytogenetic analysis revealed a
      45,X.ish der(X)t(X;Y)(p22.33;p11.2)(DXZ1+,SRY+) karyotype. Array comparative
      genome hybridization analysis showed a simple Xp terminal deletion involving SHOX
      and ARSE with the breakpoint just centromeric to PRKX, and an apparently complex
      Yp translocation with the middle Yp breakpoint just telomeric to PRKY and the
      centromeric and the telomeric Yp breakpoints around the long inverted repeats for
      the generation of a common paracentric Yp inversion. Subsequently, a long PCR
      product was obtained with an X-specific and a Y-specific primers that were
      designed on the assumption of the presence of a Yp inversion that permits the
      alignment of PRKX and PRKY in the same direction, and the translocation fusion
      point was determined to reside within a 246 bp X-Y homologous segment at the "hot
      spot A" in the 5' region of PRKX/PRKY, by sequential direct sequencing for the
      long PCR product. These results argue not only for the presence of rare 45,X-TDSD
      with Xp;Yp translocation, but also for a critical role of a common paracentric Yp
      inversion in the occurrence of PRKX/PRKY-mediated unbalanced Xp;Yp translocation.

PMID- 24088661
TI  - Parasitoid wasp virulence: A window into fly immunity.
AB  - In nature, larvae of the fruit fly Drosophila melanogaster are commonly infected
      by parasitoid wasps. Following infection, flies mount an immune response termed
      cellular encapsulation in which fly immune cells form a multilayered capsule that
      covers and kills the wasp egg. Parasitoids have thus evolved virulence factors to
      suppress cellular encapsulation. To uncover the molecular mechanisms underlying
      the antiwasp response, we and others have begun identifying and functionally
      characterizing these virulence factors. Our recent work on the Drosophila
      parasitoid Ganaspis sp.1 has demonstrated that a virulence factor encoding a
      SERCA-type calcium pump plays an important role in Ganaspis sp.1 virulence. This
      venom SERCA antagonizes fly immune cell calcium signaling and thereby prevents
      the activation of the encapsulation response. In this way, the study of wasp
      virulence factors has revealed a novel aspect of fly immunity, namely a role for
      calcium signaling in fly immune cell activation, which is conserved with human
      immunity, again illustrating the marked conservation between fly and mammalian
      immune responses. Our findings demonstrate that the cellular encapsulation
      response can serve as a model of immune cell function and can also provide
      valuable insight into basic cell biological processes. 

PMID- 24088664
TI  - Dietitian-observed macronutrient intakes of young skill and team-sport athletes:
      adequacy of pre, during, and postexercise nutrition.
AB  - CONTEXT: Sports nutrition experts recommend that team-sport athletes
      participating in intermittent high-intensity exercise for >=1 hr consume 1-4 g
      carbohydrate/kg 1-4 hr before, 30-60 g carbohydrate/hr during, and 1-1.2 g
      carbohydrate/kg/hr and 20-25 g protein as soon as possible after exercise. The
      study objective was to compare observed vs. recommended macronutrient intake of
      competitive athletes under free-living conditions. METHODS: The dietary intake of
      29 skill/team-sport athletes (14-19 y; 22 male, 7 female) was observed at a
      sports training facility by trained registered dietitians for one 24-hr period.
      Dietitians accompanied subjects to the cafeteria and field/court to record their
      food and fluid intake during meals and practices/competitions. Other dietary
      intake within the 24-hr period (e.g., snacks during class) was accounted for by
      having the subject take a picture of the food/fluid and completing a log.
      RESULTS: For male and female athletes, respectively, the mean +/- SD (and percent
      of athletes meeting recommended) macronutrient intake around exercise was 1.4 +/-
      0.6 (73%) and 1.4 +/- 1.0 (57%) g carbohydrate/kg in the 4 hr before exercise,
      21.1 +/- 17.2 (18%) and 18.6 +/- 13.2 (29%) g carbohydrate/hrr during exercise,
      1.4+/-1.1 (68%) and 0.9+/- 1.0 (43%) g carbohydrate/kg and 45.2 +/- 36.9 (73%)
      and 18.0 +/- 21.2 (43%) g protein in the 1 hr after exercise. CONCLUSION: The
      male athletes' carbohydrate and protein intake more closely approximated
      recommendations overall than that of the female athletes. The most common
      shortfall was carbohydrate intake during exercise, as only 18% of male and 29% of
      female athletes consumed 3060 g carbohydrate/hr during practice/competition.

PMID- 24088667
TI  - Novel FIG4 mutations in Yunis-Varon syndrome.
AB  - Yunis-Varon syndrome (YVS, MIM 216340) is a rare autosomal recessive disorder
      characterized by skeletal abnormalities and severe neurological impairment with
      vacuolation of the central nervous system, skeletal muscles and cartilages. Very
      recently, mutations of the FIG4 (FIG4 homolog, SAC1 lipid phosphatase domain
      containing (Saccharomyces cerevisiae)) gene, which encodes a 5'-phosphoinositide
      phosphatase essential for endosome/lysosome function have been identified as the
      cause for YVS. Interestingly, FIG4 mutations were previously reported to be
      responsible for other neurodegenerative diseases such as autosomal recessive
      Charcot-Marie-Tooth disease type 4J and autosomal dominant amyotrophic lateral
      sclerosis/primary lateral sclerosis. We analyzed a YVS patient using whole-exome
      sequencing, and identified novel biallelic FIG4 mutations: c.1750+1delG and
      c.2284_2285delCT (p.S762Wfs*3). These two mutations were mutations supposed to
      have null function. To our knowledge, this is the second report of FIG4 mutations
      in YVS and our result supports the idea that biallelic null mutations of FIG4
      cause YVS in human. 

PMID- 24088665
TI  - Resource heterogeneity can facilitate cooperation.
AB  - Although social structure is known to promote cooperation, by locally exposing
      selfish agents to their own deeds, studies to date assumed that all agents have
      access to the same level of resources. This is clearly unrealistic. Here we find
      that cooperation can be maintained when some agents have access to more resources
      than others. Cooperation can then emerge even in populations in which the
      temptation to defect is so strong that players would act fully selfishly if their
      resources were distributed uniformly. Resource heterogeneity can thus be crucial
      for the emergence and maintenance of cooperation. We also show that resource
      heterogeneity can hinder cooperation once the temptation to defect is
      significantly lowered. In all cases, the level of cooperation can be maximized by
      managing resource heterogeneity. 

PMID- 24088668
TI  - Endothelial nitric oxide synthase gene polymorphism is associated with sickle
      cell disease patients in India.
AB  - Patients with sickle cell disease (SCD) produce significantly low levels of
      plasma nitric oxide (NO) during acute vaso-occlusive crisis. In transgenic sickle
      cell mice, NO synthesized by endothelial nitric oxide synthase (eNOS) enzyme of
      vascular endothelial cells has been found to protect the mice from vaso-occlusive
      events. Therefore, the present study aims to explore possible association of eNOS
      gene polymorphism as a potential genetic modifier in SCD patients. A case control
      study involving 150 SCD patients and age- and ethnicity-matched 150 healthy
      controls were genotyped by PCR-restriction fragment length polymorphism
      techniques for three important eNOS gene polymorphisms-eNOS 4a/b, eNOS 894G>T and
      eNOS -786T>C. It was observed that SCD patients had significantly higher
      frequencies of mutant alleles besides heterozygous and homozygous mutant
      genotypes of these three eNOS gene polymorphisms and low levels of plasma nitrite
      (NO2) as compared with control groups. The SCD severe group had significantly
      lower levels of plasma NO2 and higher frequencies of mutant alleles of these
      three SNPs of eNOS gene in contrast to the SCD mild group of patients. Haplotype
      analysis revealed that frequencies of one mutant haplotype '4a-T-C' (alleles in
      order of eNOS 4a/b, eNOS 894G>T and eNOS -786T>C) were significantly high in the
      severe SCD patients (P<0.0001), whereas the frequency of a wild haplotype '4b-G
      T' was found to be significantly high (P<0.0001) in the SCD mild patients, which
      indicates that eNOS gene polymorphisms are associated with SCD patients in India
      and may act as a genetic modifier of the phenotypic variation of SCD patients. 

PMID- 24088669
TI  - Polymorphisms in the UGT1A1 gene predict adverse effects of irinotecan in the
      treatment of gynecologic cancer in Japanese patients.
AB  - Irinotecan is a key chemotherapeutic drug used to treat many tumors, including
      cervical and ovarian cancers; however, irinotecan can cause toxicity,
      particularly in the presence of uridine diphosphate glucuronosyltransferase 1A1
      (UGT1A1) gene polymorphisms, which are associated with reduced enzyme activity.
      Here, we investigated the prevalence of three different variants of UGT1A1
      (UGT1A1*6, UGT1A1*27 and UGT1A1*28) and their relationships with irinotecan
      induced adverse events in patients with gynecologic cancer, who are treated with
      lower doses of irinotecan than patients with other types of solid tumors. Fifty
      three female patients treated with irinotecan and 362 female patients not treated
      with irinotecan were screened for UGT1A1*6, UGT1A1*27 and UGT1A1*28. Homozygosity
      for UGT1A1*6 or heterozygosity for UGT1A1*6/*28 was associated with a high risk
      of severe absolute neutrophil count decrease or diarrhea (odds ratios: 16.03 and
      31.33, respectively). In contrast, serum bilirubin levels were not associated
      with irinotecan toxicity. Homozygosity for UGT1A1*6/*6 and heterozygosity for
      UGT1A1*6/*28 were associated with an increased risk of absolute neutrophil count
      and/or diarrhea in Japanese gynecologic cancer patients, despite the lower doses
      of irinotecan used in these patients. UGT1A1*6 and UGT1A1*28 are potential
      predictors of severe absolute neutrophil decrease and diarrhea caused by low-dose
      irinotecan in gynecologic cancer patients. 

PMID- 24088670
TI  - Three novel mutations in the carnitine-acylcarnitine translocase (CACT) gene in
      patients with CACT deficiency and in healthy individuals.
AB  - Carnitine-acylcarnitine translocase (CACT) and carnitine palmitoyltransferase II
      (CPT2) are key enzymes for transporting long-chain fatty acids into mitochondria.
      Deficiencies of these enzymes, which are clinically characterized by life
      threatening non-ketotic hypoglycemia and rhabdomyolysis, cannot be distinguished
      by acylcarnitine analysis performed using tandem mass spectrometry. We had
      previously reported the CPT2 genetic structure and its role in CPT2 deficiency.
      Here, we analyzed the CACT gene in 2 patients diagnosed clinically with CACT
      deficiency, 18 patients with non-traumatic rhabdomyolysis and 58 healthy
      individuals, all of whom were confirmed to have normal CPT2 genotypes. To
      facilitate CACT genotyping, we used heat-denaturing high-performance liquid
      chromatography (DHPLC), which helped identify five distinct patterns. The
      abnormal heteroduplex fragments were subjected to CACT-specific DNA sequencing.
      We found that one patient with CACT deficiency, Case 1, carried c.576G>A and
      c.199-10t>g mutations, whereas Case 2 was heterozygous for c.106-2a>t and
      c.576G>A. We also found that one patient with non-traumatic rhabdomyolysis and
      one healthy individual were heterozygous for c.804delG and the synonymous
      mutation c.516T>C, respectively. In summary, c.576G>A, c.106-2a>t and c.516T>C
      are novel CACT gene mutations. Among the five mutations identified, three were
      responsible for CACT deficiency. We have also demonstrated the successful
      screening of CACT mutations by DHPLC. 

PMID- 24088672
TI  - Vanishing of interband light absorption in a persistent spin helix state.
AB  - Spin-orbit coupling plays an important role in various properties of very
      different materials. Moreover efforts are underway to control the degree and
      quality of spin-orbit coupling in materials with a concomitant control of
      transport properties. We calculate the frequency dependent optical conductivity
      in systems with both Rashba and Dresselhaus spin-orbit coupling. We find that
      when the linear Dresselhaus spin-orbit coupling is tuned to be equal to the
      Rashba spin-orbit coupling, the interband optical conductivity disappears. This
      is taken to be the signature of the recovery of SU(2) symmetry. The presence of
      the cubic Dresselhaus spin-orbit coupling modifies the dispersion relation of the
      charge carriers and the velocity operator. Thus the conductivity is modified, but
      the interband contribution remains suppressed at most but not all photon energies
      for a cubic coupling of reasonable magnitude. Hence, such a measurement can serve
      as a diagnostic probe of engineered spin-orbit coupling. 

PMID- 24088671
TI  - Age-related changes in microRNA levels in serum.
AB  - MicroRNAs (miRNAs) are small noncoding RNAs that post-transcriptionally regulate
      gene expression by targeting specific mRNAs. Altered expression of circulating
      miRNAs have been associated with age-related diseases including cancer and
      cardiovascular disease. Although we and others have found an age-dependent
      decrease in miRNA expression in peripheral blood mononuclear cells (PBMCs),
      little is known about the role of circulating miRNAs in human aging. Here, we
      examined miRNA expression in human serum from young (mean age 30 years) and old
      (mean age 64 years) individuals using next generation sequencing technology and
      real-time quantitative PCR. Of the miRNAs that we found to be present in serum,
      three were significantly decreased in 20 older individuals compared to 20 younger
      individuals: miR-151a-5p, miR-181a-5p and miR-1248. Consistent with our data in
      humans, these miRNAs are also present at lower levels in the serum of elderly
      rhesus monkeys. In humans, miR-1248 was found to regulate the expression of mRNAs
      involved in inflammatory pathways and miR-181a was found to correlate negatively
      with the pro-inflammatory cytokines IL-6 and TNFalpha and to correlate positively
      with the anti-inflammatory cytokines TGFbeta and IL-10. These results suggest
      that circulating miRNAs may be a biological marker of aging and could also be
      important for regulating longevity. Identification of stable miRNA biomarkers in
      serum could have great potential as a noninvasive diagnostic tool as well as
      enhance our understanding of physiological changes that occur with age. 

PMID- 24088673
TI  - One hundred useful references in pediatric cardiac intensive care: the 2012
      update.
AB  - OBJECTIVE: The specialty of pediatric cardiac critical care has undergone rapid
      scientific and clinical growth in the last 25 years. The Board of Directors of
      the Pediatric Cardiac Intensive Care Society assembled an updated list of
      sentinel references focused on the critical care of children with congenital and
      acquired heart disease. We encouraged board members to select articles that have
      influenced and informed their current practice or helped to establish the
      standard of care. The objective of this article is to provide clinicians with a
      compilation and brief summary of these updated 100 useful references. DATA
      SOURCES: The list of 'One Hundred Useful References for Pediatric Cardiac
      Intensive Care' (2004) and relevant literature to the practice of cardiac
      intensive care. DATA SELECTION: A subset of Pediatric Cardiac Intensive Care
      Society board members compiled the initial list of useful references in 2004,
      which served as the basis of the new updated list. Suggestions for relevant
      articles were submitted by the Pediatric Cardiac Intensive Care Society board
      members and selected pediatric cardiac intensivists with an interest in this
      project following the Society's meeting in 2010. Articles were considered for
      inclusion if they were named in the original list from 2004 or were suggested by
      Pediatric Cardiac Intensive Care Society board members and published before
      December 31, 2011. DATA EXTRACTION: Following submission of the complete list by
      the Pediatric Cardiac Intensive Care Society board and contributing Society
      members, articles were complied by the two co-first authors (D.A., D.K.). The
      authors also performed Medline searches to ensure comprehensive inclusion of all
      relevant articles. The final list was then submitted to the Pediatric Cardiac
      Intensive Care Society board members, who ranked each publication. DATA
      SYNTHESIS: Rankings were compiled and the top 100 articles with the highest
      scores were selected for inclusion in this publication. The two co-first authors
      (D.A., D.K.) reviewed all existing summaries and developed summaries of the newly
      submitted articles. CONCLUSIONS: An updated compilation of 100 useful references
      for the critical care of children with congenital and acquired heart disease has
      been compiled and summarized here. Clinicians and trainees may wish to use this
      document as a reference for education in this complex and challenging
      subspecialty.

PMID- 24088674
TI  - Effective indium-doped zinc oxide buffer layer on silver nanowires for
      electrically highly stable, flexible, transparent, and conductive composite
      electrodes.
AB  - We demonstrate a flexible, transparent, and conductive composite electrode
      comprising silver nanowires (Ag NWs), and indium-doped zinc oxide (IZO) layers.
      IZO is sputtered onto an Ag NW layer, with the unique structural features of the
      resulting composite suitable as a flexible, transparent, conductive electrode.
      The IZO buffer layer prohibits surface oxidation of the Ag NW, and is thereby
      effective in preventing undesirable changes in electrical properties. The newly
      designed composite electrode is a promising alternative to conventional ITO films
      for the production of flexible and transparent electrodes to be applied in next
      generation flexible electronic devices. 

PMID- 24088675
TI  - Family planning and HIV: two steps forward....

PMID- 24088677
TI  - Preconception care for people living with HIV: recommendations for advancing
      implementation.
AB  - Globally, research has documented high fertility desires and intentions among HIV
      positive women. Improving implementation of preconception care (PCC) for people
      living with HIV is critical, given estimates that the majority of HIV-positive
      women who want future biological children have not received reproductive
      counseling, largely due to a lack of provider-initiated conversations. This
      article offers initial recommendations and outlines key considerations for a
      research agenda to advance PCC implementation efforts in both high-resource and
      low-resource settings. We consider who should provide PCC; where it can be
      effectively delivered; when it should be offered; and two potential
      implementation models depending on available resources. We conclude with a call
      for PCC-specific implementation science and research translation to help people
      living with HIV achieve their reproductive goals. 

PMID- 24088676
TI  - HIV-infected women on antiretroviral treatment have increased mortality during
      pregnant and postpartum periods.
AB  - OBJECTIVE: To assess the impact of pregnancy on mortality among HIV-infected
      Ugandan women initiating ART. DESIGN: Prospective cohort study. METHODS: HIV
      infected women initiating ART in the Uganda AIDS Rural Treatment Outcomes study
      were assessed quarterly for self-reported pregnancy. The association between
      pregnancy and postpartum ('pregnancy-related') follow-up periods and mortality
      was assessed with Cox proportional hazards models adjusted for age, CD4 cell
      count, plasma HIV-1 RNA levels, and ART duration. RESULTS: Three hundred and
      fifty-four women with median age 33 years (IQR: 27-37) and CD4 142 cells/MUl
      (IQR: 82-213) were followed for a median of 4.0 years (IQR: 2.5-4.8) after ART
      initiation, with 3 and 7% loss-to-follow-up at years 1 and 5. One hundred and
      nine women experienced pregnancy. Five deaths occurred during pregnancy-related
      follow-up and 16 during nonpregnancy-related follow-up, for crude mortality rates
      during the first year after ART initiation of 12.57/100 PYs and 3.53/100 PYs
      (rate ratio 3.56, 95% CI: 0.97-11.07). In adjusted models, the impact of
      pregnancy-related follow-up on mortality was highest at ART initiation (aHR:
      21.48, 95% CI: 3.73-123.51), decreasing to 13.44 (95% CI 3.28-55.11) after 4
      months, 8.28 (95% CI 2.38-28.88) after 8 months, 5.18 (95% CI: 1.36-19.71) after
      1 year, and 1.25 (95% CI: 0.10-15.58) after 2 years on ART. Four of five maternal
      deaths occurred postpartum. CONCLUSION: Pregnancy and the postpartum period were
      associated with increased mortality in HIV-infected women initiating ART,
      particularly during early ART. Contraception proximate to ART initiation, earlier
      ART initiation, and careful monitoring during the postpartum period may reduce
      maternal mortality in this setting.

PMID- 24088678
TI  - Meeting the family planning needs of women living with HIV in US government
      global health programs.
AB  - The integration of health programs, including HIV and voluntary family planning,
      is a priority for US government foreign assistance. One critical component of
      family planning and HIV integration that has significant positive health outcomes
      is ensuring that all women living with HIV have access to both a full range of
      contraceptives and safe pregnancy counseling. This article outlines the US
      government global health strategy to meet the family planning needs of women
      living with HIV based on three key principles: a focus on reproductive rights
      through voluntarism and informed choice, quality service provision through
      evidence-based programming, and development of partnerships. 

PMID- 24088679
TI  - The evolving sexual health paradigm: transforming definitions into sexual health
      practices.
AB  - Sexual health is an evolving paradigm that integrates a positive approach to
      sexuality with existing public health policy and practice for reducing the
      burdens of sexually transmitted infections, including those due to HIV. The
      sexual health paradigm rests in commitment to sexual rights, sexual knowledge,
      sexual choice, and sexual pleasure, as well as key elements of sexuality
      addressed by sexual desire, sexual arousal, and sexual function, and sexual
      behaviors. The sexual health paradigm offers new approaches to supporting general
      health and well being while reducing the burdens of sexual diseases and their
      consequences. 

PMID- 24088680
TI  - Nevirapine-based antiretroviral therapy does not reduce oral contraceptive
      effectiveness.
AB  - OBJECTIVE: To evaluate the effect of nevirapine-containing antiretroviral therapy
      (ART) on combined oral contraceptive (COC) effectiveness. DESIGN: Nonrandomized
      prospective clinical trial. METHODS: We enrolled HIV-infected women aged 18-35
      years in South Africa and Uganda who had regular menses, were sexually active,
      and had no medical contraindications to COC use. We enrolled 196 women taking
      nevirapine-containing ART and 206 women not yet eligible for ART as a control
      group. We treated all participants with low-dose COCs. Our main outcomes were
      ovulation and pregnancy rates. We estimated ovulation in the first two cycles
      using weekly serum progesterone and tested for pregnancy monthly for 24 weeks.
      RESULTS: The median age of participants was 29 and their median CD4 cell count
      was 486. In the ART group, 43 of 168 (26%) ovulated in cycle 1, 30 of 163 (18%)
      in cycle 2, and 18 of 163 (11%) in both cycles. In the non-ART group, 26 of 168
      (16%) ovulated in cycle 1, 31 of 165 (19%) in cycle 2, and 20 of 165 (12%) in
      both cycles. We found no significant difference in ovulation rates between
      groups: unadjusted odds ratio 1.36 (95% confidence interval 0.85-2.18). Pregnancy
      rates also did not differ: 10.0 per 100-women-years in the ART group and 10.1 per
      100-women-years in the non-ART group. Self-reported COC adherence, condom use,
      vaginal bleeding, and adverse events were similar. Five serious adverse events
      were reported, all in the non-ART group. CONCLUSION: ART use did not affect risk
      of ovulation or pregnancy in women taking COCs, suggesting that nevirapine
      containing ART does not interfere with COC contraceptive effectiveness.

PMID- 24088681
TI  - Effects of hormonal contraceptive use on HIV acquisition and transmission among
      HIV-discordant couples.
AB  - BACKGROUND: The risk of HIV associated with hormonal contraceptives is
      controversial. We assessed hormonal contraceptive use and HIV incidence in HIV
      discordant couples in Rakai, Uganda. METHODS: HIV-discordant couples were
      retrospectively identified from a cohort between 1999 and 2009. Hormonal
      contraception included oral contraception, depomedroxyprogesterone acetate
      (DMPA), and implants (Norplant). Poisson regression estimated adjusted incidence
      rate ratios (adjIRRs) associated with hormonal contraceptive methods. A case
      control subanalysis estimated odds ratios (ORs) of HIV associated with hormonal
      contraceptive, adjusted for viral load and age. RESULTS: We identified 190 male
      HIV-positive/female HIV-negative (M+F-) and 159 male HIV- negative/female HIV
      positive (M-F+) couples not using antiretroviral therapy or condoms. Female HIV
      incidence was 5.8/100 person-years (py) among nonhormonal contraceptive users,
      12.0/100 py among oral contraceptive users [adjIRR 2.65, 95% confidence interval
      (CI) 0.82-8.60], 4.5 among Norplant users (adjIRR: 0.89, 95% CI 0.11-7.10), and
      7.5/100 py among DMPA users (adjIRR 1.42, 95% CI 0.60-3.36). Male HIV incidence
      was 7.4/100 py during nonhormonal contraceptive use, 16.5/100 py during female
      oral contraceptive use (adjIRR 2.52, 95% CI 0.49-12.95), and 4.9/100 py with DMPA
      use (adjIRR 0.57, 95% CI 0.19-1.70). The number of female seroconverters was
      three among oral contraceptive users, one among Norplant users, and seven among
      DMPA users. Male seroconverters were two during female oral contraceptive use,
      none with Norplant use, and three with DMPA use. In a nested case-control
      analysis after adjustment for HIV viral load, the adjOR associated with oral
      contraceptive use was 1.59 (95% CI 0.32-97.85) for M+F- and 2.11 (95% CI 0.18
      25.26) for M-F+ couples. For DMPA use, the adjOR was 1.44 (95% CI 0.46-4.51) for
      M+F- and 1.40 (95% CI 0.30-6.49) for M-F+ couples. CONCLUSION: We did not observe
      significant risk of HIV acquisition or transmission with oral contraceptives or
      DMPA use in HIV discordant couples, but several point estimates were above 1.0
      and statistical power was limited.

PMID- 24088683
TI  - Hormonal contraception and HIV: the methods have confused the message.
AB  - OBJECTIVE: To examine different scenarios through which confounding by condom use
      may lead to inaccurate conclusions about the effect of hormonal contraception on
      HIV acquisition in women. DESIGN AND METHODS: Scenario analyses were conducted to
      evaluate the impact of coarse adjustment for condom use and condom misreporting
      on adjusted relative risk estimates for HIV acquisition in injectable hormonal
      contraception (IHC) users vs. nonusers. RESULTS: Analyses crudely accounting for
      condom use through a binary variable result in biased hormonal contraception
      related risk estimates if condoms are used during follow-up periods in which any
      unprotected sex is reported and condom use differs by hormonal contraception use.
      We found that over-reporting of condom use is plausible in at least one recent
      study, as demonstrated by high pregnancy rates given, reported IHC and condom
      use. Over-reporting of condom use also biases estimates, typically leading to
      underestimation of IHC-related risk if over-reporting is the same among IHC and
      non-hormonal contraception users, and overestimation of IHC-related risk if
      condom misreporting is differential by IHC use. The impact of misreported condom
      use is most pronounced in study populations with high condom uptake. CONCLUSIONS:
      Discrepant findings in hormonal contraception-HIV-related research may result
      from inadequate measurement or adjustment for confounding by condom use. Future
      studies should precisely account for condom use in statistical analyses. Studies
      should aim to quantify the degree of condom use misreporting, by comparing
      reported condom use to pregnancy, HIV or other sexually transmitted infection
      rates, and if possible, testing stored genital swabs for prostate-specific
      antigen or Y chromosome.

PMID- 24088682
TI  - Assessing the effect of hormonal contraception on HIV acquisition in
      observational data: challenges and recommended analytic approaches.
AB  - INTRODUCTION: Determining whether hormonal contraception, particularly the
      injectable contraceptive depot-medroxyprogesterone acetate (DMPA), increases a
      woman's risk of HIV acquisition is a priority question for public health.
      However, assessing the relationship between various hormonal contraceptive
      methods and HIV acquisition with observational data involves substantial analytic
      design issues and challenges. Studies to date have used inconsistent approaches
      and generated a body of evidence that is complex and challenging to interpret.
      METHODS: In January 2013, the United States Agency for International Development
      and FHI 360 supported a meeting of epidemiologists, statisticians, and content
      experts to develop recommendations for future observational analyses of hormonal
      contraception and HIV acquisition. RESULTS: Meeting participants generated
      recommendations regarding careful definition of exposure groups; handling
      potential confounders, mediators, and effect modifiers; estimating and addressing
      the magnitude of measurement error; using multiple methods to account for
      pregnancy; and exploring the potential for differential exposure to HIV-infected
      partners. Advantages and disadvantages of various statistical approaches to
      account for time-varying confounding and estimating total and direct effects were
      also discussed. CONCLUSION: Implementing these recommendations in future
      observational hormonal contraception-HIV acquisition analyses will enhance
      interpretation of existing studies and strengthen the overall evidence base for
      this complex and important area.

PMID- 24088685
TI  - Need, demand and missed opportunities for integrated reproductive health-HIV care
      in Kenya and Swaziland: evidence from household surveys.
AB  - OBJECTIVE: Little is known about the need and demand for integrated reproductive
      health and HIV services at the population level. DESIGN: Descriptive data
      analysis of household surveys collected by the Integra Initiative. METHODS:
      Household surveys were conducted among 18-49-year-olds in Kenya (N = 1752) and
      Swaziland (N = 779) in 2009. Data on fertility intentions, contraceptive use,
      sexual behaviours and HIV testing were used to determine unmet needs. Demand for
      integrated services was defined as wanting reproductive health services with
      HIV/sexually transmitted infection (STI) services within one visit. RESULTS: At
      the population level, family planning needs (90%) were higher than HIV/STI
      prevention needs: 53% (women) and 75% (men). Fewer had unmet family planning
      needs through non-use of contraceptives: 17% (women) and 27% (men); versus unmet
      HIV/STI prevention needs through inconsistent condom use: 48 and 26% of women; 51
      and 32% of men in Kenya and Swaziland, respectively. Dual need was higher for
      men: 64% (Kenya) and 73% (Swaziland) versus women (48%) with more unmet in Kenya
      (43%) compared to Swaziland (25%). Missed opportunities for integrated service
      provision were high among women: 49 and 57% with unmet family planning needs; and
      55 and 32% with unmet HIV/STI prevention needs in Kenya and Swaziland,
      respectively, used services, but did not receive the needed service. Most men
      with unmet needs were non-service users. Approximately a quarter of women wanted
      and received integrated reproductive health-HIV/STI services in both countries.
      CONCLUSIONS: Demand creation at the community level and provider-initiated
      integrated service provision are needed, using different strategies for men and
      women, to address substantial family planning and HIV/STI prevention needs.

PMID- 24088684
TI  - The complexity of contraceptives: understanding their impact on genital immune
      cells and vaginal microbiota.

PMID- 24088686
TI  - Integration of family planning into HIV services: a synthesis of recent evidence.
AB  - INTRODUCTION: Increasing access to contraception among women who enter the health
      system for HIV care is crucial to help them achieve their fertility intentions
      and reduce vertical transmission of HIV. Identifying intervention strategies that
      contribute to effective family planning/HIV service integration and synthesizing
      lessons for future integration programming and research is important to move the
      field forward. METHODS: Using a standard review methodology, we searched for
      articles in the peer-reviewed literature published between January 2008 and
      August 2013 that addressed the integration of family planning interventions into
      HIV service settings. Eligible studies were assessed in terms of methodological
      rigor; documented outcomes; and reported process and cost data. RESULTS: Twelve
      studies met our inclusion criteria. Eight studies documented significant
      increases in contraceptive use by HIV service clients, and three reported
      significant increases in completed referrals from HIV services to family planning
      clinics. The outcomes of the seven studies implemented in public sector
      facilities were more modest than the five studies embedded in clinical trials.
      Process evaluation measures for some of the studies indicated weak implementation
      of the intervention as intended. The average rigor score was low, 3.4 out of 9.
      CONCLUSION: Our review reveals an expanding evidence base for integrated family
      planning/HIV service delivery innovations. However, the modest observed effect
      under typical settings and the evidence of weak intervention implementation
      emphasize the need for stronger programmatic efforts and implementation research
      to address the health system obstacles to integrating these two essential
      services.

PMID- 24088687
TI  - Integration of family planning services into HIV care and treatment in Kenya: a
      cluster-randomized trial.
AB  - OBJECTIVE: To determine whether integrating family planning services into HIV
      care is associated with increased use of more effective contraceptive methods
      (sterilization, intrauterine device, implant, injectable or oral contraceptives).
      DESIGN: Cluster-randomized trial. SETTING: Eighteen public HIV clinics in Nyanza
      Province, Kenya. PARTICIPANTS: Women aged 18-45 years receiving care at
      participating HIV clinics; 5682 clinical encounters from baseline period
      (December 2009-February 2010) and 12,531 encounters from end-line period (July
      2011-September 2011, 1 year after site training). INTERVENTION: Twelve sites were
      randomized to integrate family planning services into the HIV clinic, whereas six
      clinics were controls where clients desiring contraception were referred to
      family planning clinics at the same facility. MAIN OUTCOME MEASURES: Increase in
      use of more effective contraceptive methods between baseline and end-line
      periods. Pregnancy rates during the follow-up year (October 2010-September 2011)
      were also compared. RESULTS: Women seen at integrated sites were significantly
      more likely to use more effective contraceptive methods at the end of the study
      [increased from 16.7 to 36.6% at integrated sites, compared to increase from 21.1
      to 29.8% at controls; odds ratio (OR) 1.81, 95% confidence interval (CI) 1.24
      2.63]. Condom use decreased non-significantly at intervention sites compared to
      controls (OR 0.64, 95% CI 0.35-1.19). No difference was observed in incident
      pregnancy in the first year after integration comparing intervention to control
      sites (incidence rate ratio 0.90; 95% CI 0.68-1.20). CONCLUSIONS: Integration of
      family planning services into HIV care clinics increased use of more effective
      contraceptive methods with a non-significant reduction in condom use. Although no
      significant reduction in pregnancy incidence was observed during the study, 1
      year may be too short a period of observation for this outcome.

PMID- 24088688
TI  - Cost, cost-efficiency and cost-effectiveness of integrated family planning and
      HIV services.
AB  - OBJECTIVE: To evaluate costs, cost-efficiency and cost-effectiveness of
      integration of family planning into HIV services. INTERVENTION: Integration of
      family planning services into HIV care and treatment clinics. DESIGN: A cluster
      randomized trial. SETTING: Twelve health facilities in Nyanza, Kenya were
      randomized to integrate family planning into HIV care and treatment; six health
      facilities were randomized to (nonintegrated) standard-of-care with separately
      delivered family planning and HIV services. MAIN OUTCOME MEASURES: We assessed
      costs, cost-efficiency (cost per additional use of more effective family
      planning), and cost-effectiveness (cost per pregnancy averted) associated with
      the first year of integration of family planning into HIV care. More effective
      family planning methods included oral and injectable contraceptives, subdermal
      implants, intrauterine device, and female and male sterilization. PATIENTS AND
      PARTICIPANTS: We collected cost data through interviews with study staff and
      review of financial records to determine costs of service integration. RESULTS:
      Integration of services was associated with an average marginal cost of $841 per
      site and $48 per female patient. Average overall and marginal costs of
      integration were associated with personnel costs [initial ($1003 vs. $872) and
      refresher ($498 vs. $330) training, mentoring ($1175 vs. $902) and supervision
      ($1694 vs. $1636)], with fewer resources required for other fixed ($18 vs. $0)
      and recurring expenses ($471 vs. $287). Integration was associated with a
      marginal cost of $65 for each additional use of more effective family planning
      and $1368 for each pregnancy averted. CONCLUSION: Integration of family planning
      and HIV services is feasible, inexpensive to implement, and cost-efficient in the
      Kenyan setting, and thus supports current Kenyan integration policy.

PMID- 24088690
TI  - Low birth weight is associated with high waist-to-height ratio in Japanese
      elementary school girls.
AB  - In Japan, the rate of low birth weight infants has increased, due to an increase
      in the number of women who smoke or are lean. A recent study showed that low
      birth weight was associated with a high adult waist-to-height ratio in adult
      Japanese women, but little data is available concerning children. In this cross
      sectional study with 568 subjects (276 boys and 292 girls), we examined the
      association between birth weight and waist-to-height ratio in 7- or 8-year-old
      Japanese children, all born at full term. The mothers of the subjects responded
      to a questionnaire about the weight of the children at birth, and physical data
      were collected from the results of measurements conducted at each school. We
      divided the subjects into two groups by the median of the birth weight (3,000 g)
      by sex to elucidate the effects of birth weight on the waist-to-height ratio.
      There were 119 boys and 164 girls and 157 boys and 128 girls in the < 3,000 g and
      >= 3,000 g birth weight groups, respectively. The Mann-Whitney U test was used to
      compare the physical conditions in the two birth weight categories. Height was
      significantly lower in the birth weight < 3,000 g group among both the boys (P <
      0.001) and girls (P < 0.001). The waist-to-height ratio was significantly higher
      in the < 3,000 g group in girls (P = 0.004), but not in the boys. Our results
      suggest that intrauterine environmental insults might have an effect on children,
      depending on sex. 

PMID- 24088689
TI  - Contraceptive discontinuation and switching among couples receiving integrated
      HIV and family planning services in Lusaka, Zambia.
AB  - OBJECTIVE: To describe predictors of contraceptive method discontinuation and
      switching behaviours among HIV-positive couples receiving couples' voluntary HIV
      counselling and testing services in Lusaka, Zambia. DESIGN: Couples were
      randomized in a factorial design to two-family planning educational intervention
      videos, received comprehensive family planning services and were assessed every 3
      months for contraceptive initiation, discontinuation and switching. METHODS: We
      modelled factors associated with contraceptive method upgrading and downgrading
      via multivariate Andersen-Gill models. RESULTS: Most women continued the initial
      method selected after randomization. The highest rates of
      discontinuation/switching were observed for injectable contraceptive and
      intrauterine device users. Time to discontinuing the more effective contraceptive
      methods or downgrading to oral contraceptives or condoms was associated with the
      women's younger age, desire for more children within the next year, heavy
      menstrual bleeding, bleeding between periods and cystitis/dysuria. Health
      concerns among women about contraceptive implants and male partners not wanting
      more children were associated with upgrading from oral contraceptives or condoms.
      HIV status of the woman or the couple was not predictive of switching or
      stopping. CONCLUSION: We found complicated patterns of contraceptive use. The
      predictors of contraception switching indicate that interventions targeted to
      younger couples that address common contraception-related misconceptions could
      improve effective family planning utilization. We recommend these findings be
      used to increase the uptake and continuation of contraception, especially long
      acting reversible contraceptive (LARC) methods, and that fertility goal based,
      LARC-focused family planning be offered as an integral part of HIV prevention
      services.

PMID- 24088691
TI  - Synthesis of heterocyclic compounds through palladium-catalyzed C-H cyclization
      processes.
AB  - Herein, we describe our development of synthetic methods for heterocyclic
      compounds based on the palladium-catalyzed carbon-hydrogen bond (C-H)
      functionalization/intramolecular carbon-heteroatom (nitrogen or sulfur) bond
      formation process. By this C-H cyclization method, we efficiently prepared
      various N-heterocycles, including indazoles, indoles, and 2-quinolinones, as well
      as S-heterocycles such as benzothiazoles and benzo[b]thiophenes. Yields are
      typically good to high and good functional-group tolerance is observed for each
      process, thereby indicating that the method provides a novel, highly applicable
      synthetic route to the abovementioned biologically important heterocyclic
      frameworks. As an application of this approach, an auto-tandem-type, one-pot
      process involving the oxidative Heck reaction and subsequent C-H cyclization
      using cinnamamides and arylboronic acids as starting materials in the presence of
      a palladium catalyst was also developed for the rapid construction of the 2
      quinolinone nucleus. 

PMID- 24088692
TI  - Methyl 5-chloro-4,5-didehydrojasmonate (J7) inhibits macrophage-derived chemokine
      production via down-regulation of the signal transducers and activators of
      transcription 1 pathway in HaCaT human keratinocytes.
AB  - Jasmonates are lipid-based stress hormones that are critical for the defense of
      plants against insects. Two naturally occurring jasmonates, jasmonic acid and
      methyl jasmonate, have recently been explored for their efficacy as anti-cancer
      agents. Furthermore, certain synthetic jasmonates (e.g., the cyclopentenone
      isoprostane J2) exert anti-inflammatory actions in lipopolysaccharide (LPS)
      challenged murine macrophages via down-regulation of chemokines and other
      inflammatory mediators. Chemokines participate in the development and progression
      of many inflammatory disorders, such as atopic dermatitis (AD) and Crohn's
      disease, as exemplified by the role of macrophage-derived chemokine (MDC/CCL22)
      in the pathology of AD. The current study therefore investigated the impact of
      jasmonate derivatives (jasmonic acid and methyl jasmonate) and their synthetic
      analogues (J2 and J7) on the expression of MDC in interferon (IFN)-gamma- and
      tumor necrosis factor (TNF)-alpha-stimulated HaCaT human keratinocytes, as well
      as the attendant mechanism of action. Jasmonic acid, methyl jasmonate, and J2
      failed to inhibit the cytokine-stimulated production of MDC. By contrast, J7
      suppressed the mRNA and protein expression levels of MDC in a dose-dependent
      manner. Moreover, J7 diminished the activation of signal transducers and
      activators of transcription 1 (STAT1), but had no inhibitory effect on the
      nuclear factor kappa B (NF-kappaB) or mitogen-activated protein kinase (MAPK)
      pathways. These results demonstrate that J7 impairs IFN-gamma- and TNF-alpha
      induced inflammatory chemokine production by targeting the STAT1 pathway. 

PMID- 24088693
TI  - Synthetic studies of cortistatin A analogue from the CD-ring fragment of vitamin
      D2.
AB  - Syntheses of analogue compounds of cortistatin A (1), an anti-angiogenic
      steroidal alkaloid from Indonesian marine sponge, were investigated by utilizing
      the CD-ring fragment of vitamin D2. The incidental preparation of a new analogue
      having CD-cis-fused skeleton and its biological evaluation revealed the
      importance of the CD-trans-fused structure for the potent and selective
      antiproliferative activity of 1 against human umbilical vein endothelial cells
      (HUVECs).

PMID- 24088694
TI  - Phosphate-ion-adsorption capability of granulated boehmite fabricated using
      organic binder (polyethylene terephthalate).
AB  - We investigated a method for producing granulated boehmite (BE) by using an
      organic binder and measured its phosphate-ion-adsorption capacity. BE was
      granulated using polyethylene terephthalate (PET), and its structure was
      characterized by scanning electron microscopy and X-ray diffraction analyses. The
      properties of granulated BE such as specific surface area, mean pore diameter,
      pore volume, amount of hydroxyl groups, and solution pH were also investigated.
      Furthermore, adsorption isotherm; effects of contact time, temperature, and
      solution pH on phosphate-ion adsorption; and recovery of phosphate ions (using
      sodium hydroxide solution) were evaluated. BE granulated by PET (BE-PET30S) could
      be successfully used for phosphate-ion removal by adsorption. The specific
      surface area and amount of hydroxyl groups of BE-PET30S were found to be 119.8
      m2/g and 1.4 mmol/g, respectively. Granulated BEs reached equilibrium adsorption
      capacities within 24 h. The phosphate-ion-adsorption rate data were fitted to the
      pseudo-second-order kinetic model (r=0.981-0.998). The adsorption isotherm data
      were fitted to both the Freundlich (0.987-0.989) and Langmuir (0.905-0.944)
      equations. Based on the thermodynamic study, it was found that the phosphate-ion
      adsorption by granulated BEs is a spontaneous and exothermic process. The
      phosphate ions adsorbed onto BE-PET30S could be easily recovered by using a
      sodium hydroxide solution (1-1000 mmol/L) and their recovery percentage was found
      to be between 63.3% and 94.0%. The results obtained from this study could be
      useful for recovering phosphate ions and preventing problems related to water
      pollution.

PMID- 24088695
TI  - Synthesis and biological evaluation of thiophene-C-glucosides as sodium-dependent
      glucose cotransporter 2 inhibitors.
AB  - The synthesis and structure-activity relationship (SAR) of thiophene-C-glucosides
      have been explored, and the human sodium-dependent glucose cotransporter 2
      (hSGLT2) inhibitory activities and rat urinary glucose excretion (UGE) effects of
      3a-f were evaluated. As a result, they showed good hSGLT2 inhibitory activities
      and rat UGE effects. In particular, the chlorothiophene derivative 3f showed
      remarkable inhibitory activity against hSGLT2. 

PMID- 24088696
TI  - Steroidal constituents from the starfish Astropecten polyacanthus and their
      anticancer effects.
AB  - Using various chromatographic methods, four new steroids, astropectenols A-D (1
      4), along with three known compounds (5-7) were isolated from a methanol extract
      of the starfish Astropecten polyacanthus. The structure elucidation was confirmed
      by spectroscopic methods, including one dimensional (1D)-, 2D-NMR and Fourier
      transform ion cyclotron resonance mass spectrometry (FT-ICR-MS). The CH2Cl2
      fraction and compound 7 exhibit potent cytotoxic effects against HL-60 human
      leukemia cells with the IC50 of 8.29 ug/mL and 2.70 uM, respectively, comparing
      to the positive control, mitoxantrone (IC50=6.80 uM). When HL-60 cells were
      treated with the CH2Cl2 fraction or compound 7, several apoptosis events like
      chromatin condensation and the increase of the population of sub-G1 hypodiploid
      cells were observed. Investigations for the possible mechanism underlying the
      induction of apoptosis showed that CH2Cl2 fraction or compound 7 induced
      apoptosis through down-regulation of Bcl-2, up-regulation of Bax, cleavage of
      caspase-9, cleavage of caspase-3 and cleavage of poly(ADP-ribose) polymerase
      (PARP) in HL-60 cells. Furthermore, the apoptosis induction of HL-60 cell by
      CH2Cl2 fraction or compound 7 was attended by the decreasing of phospho
      extracellular signal-regulated kinase (ERK) 1/2 and C-myc. These results
      indicated that the CH2Cl2 fraction and compound 7 could induce the apoptosis of
      HL-60 cells via the inactivation of ERK 1/2 and the decrease of C-myc. Our
      finding suggested the potential using of the CH2Cl2 fraction and compound 7 for
      leukemia treatment.

PMID- 24088697
TI  - Chemistry of ecteinascidins. Part 4: preparation of 2'-N-acyl ecteinascidin 770
      derivatives with improved cytotoxicity profiles.
AB  - We report herein eleven 2'-N-acyl derivatives that were prepared from
      ecteinascidin 770 (Et 770: 1b) via 18,6'-O-bisallyl protected compound (4) in
      excellent yields. 2'-N-Acyl derivatives (6a-k) generally showed higher
      cytotoxicity than 1b. Among them, 3-quinolineacyl derivative (6g) and 4
      fluorocinnamoyl derivative (6h) exhibited approximately 50- and 70-fold higher
      cytotoxicity to the HCT116 human colon carcinoma cell line, respectively, than
      1b. Both compounds are potent inhibitors of the in vitro growth of several tumor
      cells and are therefore promising leads for further optimization. We also report
      the transformation of 1b into Et 788 (3), which is the first example of an
      ecteinascidin derivative having a primary amide at C-21 position. 

PMID- 24088698
TI  - Three new iridoid glycosides from the fruit of gardenia jasminoides var.
      radicans.
AB  - Three new iridoid glycosides, 6"-O-trans-feruloylgenipin gentiobioside (1), 2'-O
      trans-p-coumaroylgardoside (2), 2'-O-trans-feruloylgardoside (3), were isolated
      from the fruit of Gardenia jasminoides var. radicans MAKINO (Rubiaceae). The
      structures of these compounds were elucidated on the basis of MS, NMR spectra
      analysis, glycoside hydrolysis, and sugar derivatization coupled with HPLC
      analysis. 

PMID- 24088699
TI  - Inhibitory effect of four triterpenoids from trichilia connaroides on nitric
      oxide production in lipopolysaccharide-stimulated RAW264.7 cells.
AB  - Two new highly rearranged trichiliton-type limonoids (trichilitons G-H, 1-2), and
      two new cycloartane-type triterpenoids, 21-(E)-coumaroyloxy-5alpha-cycloart-24
      ene-3,23-dione (3) and 21-(E)-feruloyloxy-5alpha-cycloart-24-ene-3,23-dione (4),
      were isolated from the stem and bark of Trichilia connaroides. These isolates
      were elucidated on the basis of detailed spectroscopic analysis, and inhibitory
      effect of these compounds on lipopolysaccharide-induced nitric oxide production
      in mouse macrophage RAW264.7 cells was evaluated. 

PMID- 24088700
TI  - Benzylidene 2-aminoimidazolones derivatives: synthesis and in vitro evaluation of
      anti-tumor carcinoma activity.
AB  - A series of benzylidene 2-aminoimidazolones derivatives were synthesized. Most
      compounds displayed strong inhibitory activity on the proliferation of human
      HepG2 cells in vitro. The active compounds were further evaluated by 3-(4,5
      dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay against five
      human cancer cell lines in vitro. Compound 2b exhibited the strongest antitumor
      activities with IC50 values ranging from 12.87-17.10 uM which were nearly 1-3.5
      fold less than that of 5-FU (IC50=18.39-56.12 uM) in vitro. Furthermore, compound
      2b could induce SMMC-7721 cell apoptosis in a dose-dependent manner. Therefore,
      our novel findings may provide a new framework for the design of new benzylidene
      2-aminoimidazolones derivatives for the treatment of cancer.

PMID- 24088701
TI  - Absolute structures of stemona-lactam S and tuberostemospiroline, alkaloids from
      stemona tuberosa.
AB  - A new alkaloid, stemona-lactam S, and a known alkaloid, tuberostemospiroline,
      were isolated from the roots of Stemona tuberosa LOUR. (Stemonaceae). Their
      structures and absolute stereochemistry were established by X-ray crystallography
      and vibrational circular dichroism. 

PMID- 24088702
TI  - Antibacterial activity of some 5-dialkylaminomethylhydantoins and related
      derivatives.
AB  - In connection with our studies on antibacterial compounds in the class of 5
      dialkylaminomethylhydantoins against Gram-negative (Escherichia coli) and Gram
      positive (Staphylococcus aureus) strains, some molecular modifications were
      attempted. The antibacterial activities of all of the synthesized hydantoin
      derivatives were evaluated. Among the hydantoin derivatives designed in this
      study, C2-symmetrical twin-drug type compound (7) showed the highest level of
      antibacterial activity against S. aureus strain.

PMID- 24088703
TI  - Synthesis of novel benzo-fused heteroaryl derivatives as Ca2+/calmodulin
      dependent protein kinase II inhibitors.
AB  - Based on the structure activity relationship of 2-(4-phenoxybenzoyl)-5
      hydroxyindole (1), a novel structural class of Ca2+/calmodulin-dependent protein
      kinase II (CaMKII) inhibitors were synthesized. We show in this study that the
      acidic proton at the N(1)-position of the indole moiety is not essential for
      CaMKII inhibitory activity. Among the synthesized compounds, we found the
      benzofuran and benzothiazole derivative as promising scaffolds for the
      developement of potent CaMKII inhibitors. In particular, compounds 8 and 14
      inhibited CaMKII with IC50 values of 24 nM and 32 nM, respectively.

PMID- 24088704
TI  - Home blood pressure measurement as a screening tool for hypertension in a web
      based worksite health promotion programme.
AB  - BACKGROUND: Guidelines on home blood pressure measurement (HBPM) recommend taking
      at least 12 measurements. For screening purposes, however, it is preferred to
      reduce this number. We therefore derived and validated cut-off values to
      determine hypertension status after the first duplicate reading of a HBPM series
      in a web-based worksite health promotion programme. METHOD: Nine hundred forty
      five employees were included in the derivation and 528 in the validation cohort,
      which was divided into a normal (n = 297) and increased cardiometabolic risk
      subgroup (n = 231), and a subgroup with a history of hypertension (n = 98). Six
      duplicate home measurements were collected during three consecutive days.
      Systolic and diastolic readings at the first duplicate measurement were used as
      predictors for hypertension in a multivariate logistic model. Cut-off values were
      determined using receiver operating characteristics analysis. RESULTS: Upper (>=
      150 or >= 95 mmHg) and lower limit (<135 and <80 mmHg) cut-off values were
      derived to confirm or reject presence of hypertension after one duplicate
      reading. The area under the curve was 0.94 (standard error 0.01, 95% confidence
      interval 0.93-0.95). In 62.5% of participants, hypertension status was
      determined, with 1.1% false positive and 4.7% false negatives. Performance was
      similar in participants with high and low cardiometabolic risk, but worse in
      participants with a history of hypertension (10.4% false negatives). CONCLUSION:
      One duplicate home reading is sufficient to accurately assess hypertension status
      in 62.5% of participants, leaving 37.5% in which the whole HBPM series needs to
      be completed. HBPM can thus be reliably used as screening tool for hypertension
      in a working population.

PMID- 24088705
TI  - Independent contractor model for GPs has had its day, says RCGP chairwoman.

PMID- 24088707
TI  - Pretreatment 25-hydroxyvitamin D levels and durability of anti-tumor necrosis
      factor-alpha therapy in inflammatory bowel diseases.
AB  - INTRODUCTION: Emerging evidence supports an immunologic role for 25
      hydroxyvitamin D (25(OH)D) in inflammatory bowel disease (IBD). Here we examined
      if pretreatment vitamin D status influences durability of anti-tumor necrosis
      factor (TNF)-alpha therapy in patients with Crohn's disease (CD) or ulcerative
      colitis (UC). METHODS: All IBD patients who had plasma 25(OH)D level checked <3
      months prior to initiating anti-TNF-alpha therapy were included in this
      retrospective single-center cohort study. Our main predictor variable was
      insufficient plasma 25(OH)D (<30 ng/mL). Cox proportional hazards model adjusting
      for potential confounders was used to identify the independent effect of
      pretreatment vitamin D on biologic treatment cessation. RESULTS: Our study
      included 101 IBD patients (74 CD; median disease duration 9 years). The median
      index 25(OH)D level was 27 ng/mL (interquartile range, 20-33 ng/mL). One-third of
      the patients had prior exposure to anti-TNF-alpha therapy. On multivariate
      analysis, patients with insufficient vitamin D demonstrated earlier cessation of
      anti-TNF-alpha therapy (hazard ratio [HR], 2.13; 95% confidence interval [CI],
      1.03-4.39; P = .04). This effect was significant in patients who stopped
      treatment for loss of response (HR, 3.49; 95% CI, 1.34-9.09) and stronger for CD
      (HR, 2.38; 95% CI, 0.95-5.99) than UC (P = NS). CONCLUSIONS: Our findings suggest
      that vitamin D levels may influence durability of anti-TNF-alpha induction and
      maintenance therapy. Larger cohort studies and clinical trials of supplemental
      vitamin D use with disease activity as an end point may be warranted.

PMID- 24088708
TI  - Metal-enhanced fluorescence.

PMID- 24088706
TI  - MAL hypermethylation is a tissue-specific event that correlates with MAL mRNA
      expression in esophageal carcinoma.
AB  - MAL promoter hypermethylation was examined in 260 human esophageal specimens
      using real-time quantitative methylation-specific PCR (qMSP). MAL
      hypermethylation showed highly discriminative ROC curve profiles which clearly
      distinguished esophageal adenocarcinomas (EAC) from both esophageal squamous cell
      carcinomas (ESCC) and normal esophagus (NE). Both MAL methylation frequency and
      normalized methylation value (NMV) were significantly higher in Barrett's
      esophagus (BE), dysplastic BE, and EAC than in ESCC or in NE. Among matched NE
      and EAC samples, MAL NMVs in EAC were significantly higher than in corresponding
      NE. There was a significant correlation between MAL hypermethylation and BE
      segment length. Treatment with 5-aza-2'-deoxycytidine reversed MAL methylation
      and reactivated MAL mRNA expression in OE33 EAC cells. MAL mRNA levels in EACs
      with unmethylated MAL were significantly higher than in EACs with methylated MAL.
      MAL hypermethylation is a common, tissue-specific event in human EAC and
      correlates with clinical neoplastic progression risk factors. 

PMID- 24088710
TI  - Predicting cycling performance in trained to elite male and female cyclists.
AB  - In high-performance cycling, it is important to maintain a healthy balance
      between training load and recovery. Recently a new submaximal cycle test, known
      as the Lamberts and Lambert Submaximal Cycle Test (LSCT), has been shown to be
      able to accurately predict cycling performance in 15 well-trained cyclists. The
      aim of this study was to determine the predictive value of the LSCT in 102
      trained to elite cyclists (82 men and 20 women). All cyclists performed an LSCT
      test followed by a peak-power-output (PPO) test, which included respiratory-gas
      analysis for the determination of maximal oxygen consumption (VO(2max)). They
      then performed the LSCT test followed by a 40-km time trial (TT) 72 h later.
      Average power output during the 3 stages of the LSCT increased from 31%, 60%, and
      79% of PPO, while the ratings of perceived exertion increased from 8 to 13 to 16.
      Very good relationships were found between actual and LSCT-predicted PPO (r =
      .98, 95%CI: .97-.98, P < .0001), VO(2max) (r = .96, 95%CI: .97-.99, P < .0001)
      and 40-km-TT time (r = .98, 95%CI: .94-.97, P < .0001). No gender differences
      were found when predicting cycling performance from the LSCT (P = .95). The
      findings of this study show that the LSCT is able to accurately predict cycling
      performance in trained to elite male and female cyclists and potentially can be
      used to prescribe and fine-tune training prescription in cycling.

PMID- 24088711
TI  - Darwinian evolution in a translation-coupled RNA replication system within a cell
      like compartment.
AB  - The ability to evolve is a key characteristic that distinguishes living things
      from non-living chemical compounds. The construction of an evolvable cell-like
      system entirely from non-living molecules has been a major challenge. Here we
      construct an evolvable artificial cell model from an assembly of biochemical
      molecules. The artificial cell model contains artificial genomic RNA that
      replicates through the translation of its encoded RNA replicase. We perform a
      long-term (600-generation) replication experiment using this system, in which
      mutations are spontaneously introduced into the RNA by replication error, and
      highly replicable mutants dominate the population according to Darwinian
      principles. During evolution, the genomic RNA gradually reinforces its
      interaction with the translated replicase, thereby acquiring competitiveness
      against selfish (parasitic) RNAs. This study provides the first experimental
      evidence that replicating systems can be developed through Darwinian evolution in
      a cell-like compartment, even in the presence of parasitic replicators. 

PMID- 24088712
TI  - Effete, an E2 ubiquitin-conjugating enzyme with multiple roles in Drosophila
      development and chromatin organization.
AB  - The Drosophila effete gene encodes an extremely conserved class I E2 ubiquitin
      conjugating enzyme. Growing evidence indicates that Eff is involved in many
      cellular processes including eye development, maintenance of female germline stem
      cells, and regulation of apoptosis. Eff is also a major component of Drosophila
      chromatin and it is particularly enriched in chromatin with repressive
      properties. In addition, Eff is required for telomere protection and to prevent
      telomere fusion. Consistent with its multiple roles in chromatin maintenance, Eff
      is also one of the rare factors that modulate both telomere-induced and
      heterochromatin-induced position effect variegation. 

PMID- 24088713
TI  - SET7/9-dependent methylation of ARTD1 at K508 stimulates poly-ADP-ribose
      formation after oxidative stress.
AB  - ADP-ribosyltransferase diphtheria toxin-like 1 (ARTD1, formerly PARP1) is
      localized in the nucleus, where it ADP-ribosylates specific target proteins. The
      post-translational modification (PTM) with a single ADP-ribose unit or with
      polymeric ADP-ribose (PAR) chains regulates protein function as well as protein
      protein interactions and is implicated in many biological processes and diseases.
      SET7/9 (Setd7, KMT7) is a protein methyltransferase that catalyses lysine
      monomethylation of histones, but also methylates many non-histone target proteins
      such as p53 or DNMT1. Here, we identify ARTD1 as a new SET7/9 target protein that
      is methylated at K508 in vitro and in vivo. ARTD1 auto-modification inhibits its
      methylation by SET7/9, while auto-poly-ADP-ribosylation is not impaired by prior
      methylation of ARTD1. Moreover, ARTD1 methylation by SET7/9 enhances the
      synthesis of PAR upon oxidative stress in vivo. Furthermore, laser irradiation
      induced PAR formation and ARTD1 recruitment to sites of DNA damage in a SET7/9
      dependent manner. Together, these results reveal a novel mechanism for the
      regulation of cellular ARTD1 activity by SET7/9 to assure efficient PAR formation
      upon cellular stress. 

PMID- 24088715
TI  - Operando magnetic resonance: monitoring the evolution of conversion and product
      distribution during the heterogeneous catalytic ethene oligomerisation reaction.
AB  - Operando magnetic resonance (MR) spectroscopy has been used to follow an ethene
      oligomerisation reaction performed at 110  degrees C, 28 barg over a 1 wt%
      Ni/SiO2-Al2O3 catalyst. Spectra acquired over the timecourse of the reaction
      allow the calculation of conversion and product distribution as a function of
      time-on-stream. 

PMID- 24088714
TI  - Structure of a bacterial putative acetyltransferase defines the fold of the human
      O-GlcNAcase C-terminal domain.
AB  - The dynamic modification of proteins by O-linked N-acetylglucosamine (O-GlcNAc)
      is an essential posttranslational modification present in higher eukaryotes.
      Removal of O-GlcNAc is catalysed by O-GlcNAcase, a multi-domain enzyme that has
      been reported to be bifunctional, possessing both glycoside hydrolase and histone
      acetyltransferase (AT) activity. Insights into the mechanism, protein substrate
      recognition and inhibition of the hydrolase domain of human OGA (hOGA) have been
      obtained via the use of the structures of bacterial homologues. However, the
      molecular basis of AT activity of OGA, which has only been reported in vitro, is
      not presently understood. Here, we describe the crystal structure of a putative
      acetyltransferase (OgpAT) that we identified in the genome of the marine
      bacterium Oceanicola granulosus, showing homology to the hOGA C-terminal AT
      domain (hOGA-AT). The structure of OgpAT in complex with acetyl coenzyme A
      (AcCoA) reveals that, by homology modelling, hOGA-AT adopts a variant AT fold
      with a unique loop creating a deep tunnel. The structures, together with
      mutagenesis and surface plasmon resonance data, reveal that while the bacterial
      OgpAT binds AcCoA, the hOGA-AT does not, as explained by the lack of key residues
      normally required to bind AcCoA. Thus, the C-terminal domain of hOGA is a
      catalytically incompetent 'pseudo'-AT. 

PMID- 24088716
TI  - The role of renal denervation for the treatment of resistant hypertension.
AB  - Hypertension affects more than one-fourth of the adult population worldwide and
      is a major risk factor for cardiovascular and kidney disease. Currently, the
      majority of patients with hypertension do not reach goal blood pressure (BP)
      targets, and cardiovascular risk is increased further for patients with treatment
      resistant hypertension, defined as office BP above goal despite pharmacological
      treatment with three or more antihypertensive medications at optimal doses
      including a diuretic. Although missed diagnosis of secondary forms of
      hypertension, physician inertia and non-adherence with prescribed medication are
      important contributors to the phenomenon of resistant hypertension that need to
      be addressed, there is a need for alternative therapeutic approaches. Renal
      sympathetic denervation is a minimally invasive endovascular procedure that
      disrupts renal efferent and afferent neural connections, both of which are
      important regulators of BP control. Limited data from recent clinical trials
      indicate that this approach is safe and effectively lowers BP in patients with
      treatment-resistant hypertension. Accumulating data is emerging to suggest that
      renal sympathetic denervation may also have utility beyond treatment-resistant
      hypertension. This review aims to briefly summarize the existing evidence for the
      use of renal denervation (RDN) in patients with treatment-resistant hypertension
      and to explore the potential utility of RDN in other pathological states
      associated with sympathetic dysfunction. 

PMID- 24088717
TI  - Association of neck circumference and obesity status with elevated blood pressure
      in children.
AB  - High blood pressure (BP) and overweight/obesity are increasingly prevalent in
      children. We examined the associations of excess weight indicators including neck
      circumference (NC) and body mass index (BMI) with high BP in children. We
      hypothesized that high NC is associated with elevated BP. We utilized cross
      sectional anthropometric and BP data on 1058 children aged 6-18 years. Patients
      were classified into weight and NC categories according to published guidelines.
      Prehypertension was defined as systolic or diastolic BP levels between 90th and
      95th percentile for gender, age and height. Hypertension signifies systolic
      and/or diastolic BP levels >= 95th percentile for age, gender and height. The
      prevalence of elevated BP was 29.2% (prehypertension=10.1%, hypertension=19.1%).
      The prevalence of overweight and obesity was 19.0 and 18.7%, respectively. Rates
      of wide NC increased progressively with BMI categories by 8.8, 29.4 and 68.7%
      among normal weight, overweight and obese children, respectively. Within each BMI
      category, the unadjusted odds ratio for elevated BP was significantly higher in
      children with wide NC than those with normal NC (normal weight OR=1.78 (1.0-3.1),
      P=0.04); overweight OR=2.74 (1.5-5.2), P=0.001); obese OR=2.44 (1.3-4.6),
      P=0.006)). Increasing NC and BMI are associated with elevated BP in children.
      Joint presence of wide NC and high BMI is associated with significantly high
      rates of elevated BP. NC measurement may be a helpful tool to detect the presence
      of elevated BP in children.

PMID- 24088718
TI  - Quantity and variety in fruit and vegetable intake and risk of coronary heart
      disease.
AB  - BACKGROUND: Dietary guidelines recommend increasing fruit and vegetable intake
      and, most recently, have also suggested increasing variety. OBJECTIVE: We
      prospectively examined the independent roles of quantity and variety in fruit and
      vegetable intake in relation to incident coronary heart disease (CHD). DESIGN: We
      prospectively followed 71,141 women from the Nurses' Health Study (1984-2008) and
      42,135 men from the Health Professionals Follow-Up Study (1986-2008) who were
      free of diabetes, cardiovascular diseases, and cancer at baseline. Diet was
      assessed by using a validated questionnaire and updated every 4 y. Variety was
      defined as the number of unique fruit and vegetables consumed at least once per
      week. Potatoes, legumes, and fruit juices were not included in our definition of
      fruit and vegetables. RESULTS: During follow-up, we documented 2582 CHD cases in
      women and 3607 cases in men. In multivariable analyses, after adjustment for
      dietary and nondietary covariates, those in the highest quintile of fruit and
      vegetable intake had a 17% lower risk (95% CI: 9%, 24%) of CHD. A higher
      consumption of citrus fruit, green leafy vegetables, and beta-carotene- and
      vitamin C-rich fruit and vegetables was associated with a lower CHD risk.
      Conversely, quantity-adjusted variety was not associated with CHD. CONCLUSIONS:
      Our data suggest that absolute quantity, rather than variety, in fruit and
      vegetable intake is associated with a significantly lower risk of CHD.
      Nevertheless, consumption of specific fruit and vegetable subgroups was
      associated with a lower CHD risk.

PMID- 24088719
TI  - Associations between food groups, dietary patterns, and cardiorespiratory fitness
      in the Coronary Artery Risk Development in Young Adults study.
AB  - BACKGROUND: Few studies have investigated the association between overall diet
      and cardiorespiratory fitness (CRF). OBJECTIVE: We aimed to investigate
      associations of food groups, a diet-quality score, and dietary patterns with CRF
      in black and white adults. DESIGN: We included 2632 participants aged 38-50 y who
      attended the year 20 exam of the Coronary Artery Risk Development in Young Adults
      (CARDIA) study and Coronary Artery Risk Development in Young Adults Fitness Study
      (CFS) conducted in 2005-2006. Diet was assessed by using a validated diet
      history. A dietary score and 2 types of patterns were included as follows: the a
      priori diet-quality score and meat and fruit-vegetable dietary patterns derived
      from principal components analysis. CRF was assessed by using a graded exercise
      treadmill test. Linear regression models regressed the treadmill duration on food
      groups and dietary scores and patterns overall and in race-sex subgroups.
      RESULTS: Grains (whole and refined), processed meats, and beverages (coffee, meal
      replacement drinks, beer, and wine) were positively associated with the treadmill
      duration overall; whole fruit (not juices), organ meats, fried meats and fish,
      and soy and nondairy products were negatively associated. The a priori diet
      quality score was positively associated with the duration overall and in all race
      sex subgroups (P <0.05) except black men. The meat pattern was negatively
      associated with the duration in white men and white women only. The fruit
      vegetable pattern was positively associated with duration in white women only.
      CONCLUSIONS: Overall, the a priori diet-quality score was positively associated
      with CRF in this cohort of black and white adults, whereas the meat dietary
      pattern was negatively associated only in whites. The CARDIA study and CFS were
      registered at clinicaltrials.gov as NCT00005130 and NCT00106457, respectively.

PMID- 24088720
TI  - Genetic and environmental influences on sodium intake determined by using half
      day urine samples: the Healthy Twin Study.
AB  - BACKGROUND: Salt is essential in our diet, but excess intake is a well
      established risk factor for hypertension. The presence and importance of genetic
      contributions to salt intake, however, are not well understood. OBJECTIVE: The
      aim of this study was to examine whether a genetic predisposition and an
      environmental influence exist for sodium intake and salt habit. DESIGN: In a twin
      family cohort, half-day urine samples from 1204 individuals (133 pairs of
      monozygotic twins, 29 pairs of dizygotic twins, and 880 singletons) were
      collected to assess 24-h sodium intakes. Daily total sodium intake, sodium
      density per calorie (Na-D), and salt habit questions were analyzed with
      adjustment for other epidemiologic characteristics. We calculated heritability
      (h2) and intraclass correlations to examine the genetic and shared environmental
      contributions to total sodium intake traits. RESULTS: The average sodium intake
      was 208.4 +/- 107.0 mmol/d. Men had a higher absolute sodium intake (242.6 +/-
      117.4 mmol/d), but Na-D did not differ by sex. Moderate genetic influences
      existed (h2 = 0.31-0.34) for sodium intake and Na-D. We also found that sharing
      current residence rather than being a family member explained 22% of the variance
      in Na-D. CONCLUSION: Our findings suggest that both genetic predisposition and
      shared environment contribute to sodium intakes and salt habits alike.

PMID- 24088721
TI  - Infant iron status affects iron absorption in Peruvian breastfed infants at 2 and
      5 mo of age.
AB  - BACKGROUND: Effects of prenatal iron supplementation on maternal postpartum iron
      status and early infant iron homeostasis remain largely unknown. OBJECTIVE: We
      examined iron absorption and growth in exclusively breastfed infants in relation
      to fetal iron exposure and iron status during early infancy. DESIGN:
      Longitudinal, paired iron-absorption (58Fe) studies were conducted in 59
      exclusively breastfed Peruvian infants at 2-3 mo of age (2M) and 5-6 mo of age
      (5M). Infants were born to women who received >= 5100 or <= 1320 mg supplemental
      prenatal Fe. Iron status was assessed in mothers and infants at 2M and 5M.
      RESULTS: Infant iron absorption from breast milk averaged 7.1% and 13.9% at 2M
      and 5M. Maternal iron status (at 2M) predicted infant iron deficiency (ID) at 5M.
      Although no infants were iron deficient at 2M, 28.6% of infants had depleted iron
      stores (ferritin concentration <12 MUg/L) by 5M. Infant serum ferritin decreased
      (P < 0.0001), serum transferrin receptor (sTfR) increased (P < 0.0001), and serum
      iron decreased from 2M to 5M (P < 0.01). Higher infant sTfR (P < 0.01) and breast
      milk copper (P < 0.01) predicted increased iron absorption at 5M. Prenatal iron
      supplementation had no effects on infant iron status or breast-milk nutrient
      concentrations at 2M or 5M. However, fetal iron exposure predicted increased
      infant length at 2M (P < 0.01) and 5M (P < 0.05). CONCLUSIONS: Fetal iron
      exposure affected early infant growth but did not significantly improve iron
      status or absorption. Young, exclusively breastfed infants upregulated iron
      absorption when iron stores were depleted at both 2M and 5M.

PMID- 24088723
TI  - Three years after the launch of the Helsinki Declaration on patient safety in
      anaesthesiology: the history, the progress and quite a few challenges for the
      future.

PMID- 24088722
TI  - Experimental sleep curtailment causes wake-dependent increases in 24-h energy
      expenditure as measured by whole-room indirect calorimetry.
AB  - BACKGROUND: Epidemiologic evidence has shown a link between short sleep and
      obesity. Clinical studies suggest a role of increased energy intake in this
      relation, whereas the contributions of energy expenditure (EE) and substrate
      utilization are less clearly defined. OBJECTIVE: Our aim was to investigate the
      effects of sleep curtailment on 24-h EE and respiratory quotient (RQ) by using
      whole-room indirect calorimetry under fixed-meal conditions. DESIGN: Ten females
      aged 22-43 y with a BMI (in kg/m2) of 23.4-27.5 completed a randomized, crossover
      study. Participants were studied under short- (4 h/night) and habitual- (8
      h/night) sleep conditions for 3 d, with a 4-wk washout period between visits.
      Standardized weight-maintenance meals were served at 0800, 1200, and 1900 with a
      snack at 1600. Measures included EE and RQ during the sleep episode on day 2 and
      continuously over 23 h on day 3. RESULTS: Short compared with habitual sleep
      resulted in significantly higher (+/- SEM) 24-h EE (1914.0 +/- 62.4 compared with
      1822.1 +/- 43.8 kcal; P = 0.012). EE during the scheduled sleep episode (0100
      0500 and 2300-0700 in short- and habitual-sleep conditions, respectively) and
      across the waking episode (0800-2300) were unaffected by sleep restriction. RQ
      was unaffected by sleep restriction. CONCLUSIONS: Short compared with habitual
      sleep is associated with an increased 24-h EE of ~92 kcal (~5%)--lower than the
      increased energy intake observed in prior sleep-curtailment studies. This finding
      supports the hypothesis that short sleep may predispose to weight gain as a
      result of an increase in energy intake that is beyond the modest energy costs
      associated with prolonged nocturnal wakefulness.

PMID- 24088724
TI  - Anaesthetist support during sedation for patients undergoing minimally invasive
      procedures outside the operating room: the call for more research.

PMID- 24088725
TI  - Mycophenolate mofetil combination therapy improves survival after liver
      transplantation. A single-center retrospective analysis.
AB  - BACKGROUND: Because the immunosuppressive regimen is a modifiable risk factor
      after orthotopic liver transplantation (OLT), physicians are nowadays aiming at
      an optimized and individualized strategy for each patient. The aim of this
      retrospective study was to examine the impact of different immunosuppressive
      regimens on the long-term outcome post-OLT based on routine, real-life
      situations, with particular focus on the subgroups of patients with HCC or HCV.
      MATERIAL AND METHODS: Our study included 186 patients who underwent OLT between
      1999 and 2008 at the University Hospital Heidelberg, Germany with an available
      minimum follow-up period of 12 months. Data were collected pre-transplantation,
      and at 3 months, 6 months, and 12 months post-OLT and every 6 months afterwards.
      RESULTS: We found a statistically significant better 5-year survival in the
      calcineurin inhibitor (CNI) + mycophenolate mofetil (MMF) group vs. CNI - MMF
      (p=0.01) in the whole study group, in the HCC group (p=0.008), and in the HCV
      group (p=0.0163). Furthermore, there was a trend towards a prolonged HCV relapse
      free 5-year survival rate in the CNI + MMF group of 85.6% vs. 70.8% in the CNI -
      MMF group, a trend towards a lower incidence of death secondary to infection
      (30.8% vs. 69.2%), and a trend towards lower rates of acute rejections (22.6% vs.
      29%). The type of CNI administered was irrelevant in all respects. CONCLUSIONS:
      MMF added to immunosuppressive therapy improves patient survival in OLT
      recipients in general, as well as in patients with HCC and HCV. Prospective
      studies are needed to determine if a broader application of MMF post-OLT in
      combination with CNI-tapering could lead to further outcome improvement.

PMID- 24088726
TI  - Deeper insight into the reducing biotransformation of bupropion in the human
      liver.
AB  - Bupropion is widely used as an antidepressant drug and also as a smoking
      cessation aid. In humans, this drug is extensively metabolized to form several
      metabolites. Oxidised hydroxybupropion and two reduced metabolites,
      threohydrobupropion and erythrohydrobupropion, are major metabolites. All of
      these metabolites are considered to be active. Although the oxidative metabolic
      pathway and the central role of CYP2B6 are known, the enzymes that participate in
      the reduction have not been identified to date. The aim of this study was to
      confirm the role of human liver subcellular fractions in the metabolism of
      bupropion and elucidate the contribution of particular carbonyl-reducing enzymes.
      An HPLC method for the determination of bupropion metabolites was utilised.
      Bupropion is reduced to threohydrobupropion and less to erythrohydrobupropion in
      human liver cytosol, microsomes and also mitochondria. Surprisingly, intrinsic
      clearance for formation of both metabolites is the highest in mitochondrial
      fraction. Moreover this study provides the first direct evidence that 11beta
      hydroxysteroid dehydrogenase 1, AKR1C1, AKR1C2, AKR1C3 and CBR1 participate in
      the reducing biotransformation of bupropion in vitro. The enzyme kinetics of all
      of these reductases was investigated and kinetic parameters were calculated.

PMID- 24088727
TI  - Involvement of AP-1 and NF-kappaB in the up-regulation of P-gp in vinblastine
      resistant Caco-2 cells.
AB  - Caco-2 is a widely used cell model in drug absorption and P-glycoprotein (P-gp,
      MDR1) substrate identification. Long-term vinblastine treatment of Caco-2 cells
      could increase the expression of P-gp; thus, the vinblastine resistant Caco-2
      (Caco-2 vbl) cells can be used as a rapid and sensitive alternative model in
      identifying P-gp substrates. The mechanism of P-gp induction in this model is not
      clear; this study was therefore intended to clarify the possible factors involved
      in P-gp up-regulation in Caco-2 vbl cells. Since vinblastine is the inducer of
      both activator protein-1 (AP-1) and nuclear factor kappa B (NF-kappaB), we
      investigated the role of AP-1 and NF-kappaB in the regulation of MDR1 gene
      expression. Our results indicated that the AP-1 and NF-kappaB luciferase activity
      was higher in Caco-2 vbl cells than that in Caco-2 cells according to reporter
      gene assay. The mRNA expression of AP-1 subunit c-Jun and NF-kappaB was increased
      in Caco-2 vbl cells. The c-Jun inhibitor SP600125 and NF-kappaB inhibitor
      pyrrolidine dithiocarbamate (PDTC) suppressed the expression of MDR1 mRNA in Caco
      2 vbl cells. In conclusion, this study provides the evidence that AP-1 and NF
      kappaB are involved in the P-gp induction in Caco-2 vbl cells.

PMID- 24088728
TI  - Characterization of GM events by insert knowledge adapted re-sequencing
      approaches.
AB  - Detection methods and data from molecular characterization of genetically
      modified (GM) events are needed by stakeholders of public risk assessors and
      regulators. Generally, the molecular characteristics of GM events are
      incomprehensively revealed by current approaches and biased towards detecting
      transformation vector derived sequences. GM events are classified based on
      available knowledge of the sequences of vectors and inserts (insert knowledge).
      Herein we present three insert knowledge-adapted approaches for characterization
      GM events (TT51-1 and T1c-19 rice as examples) based on paired-end re-sequencing
      with the advantages of comprehensiveness, accuracy, and automation. The
      comprehensive molecular characteristics of two rice events were revealed with
      additional unintended insertions comparing with the results from PCR and Southern
      blotting. Comprehensive transgene characterization of TT51-1 and T1c-19 is shown
      to be independent of a priori knowledge of the insert and vector sequences
      employing the developed approaches. This provides an opportunity to identify and
      characterize also unknown GM events. 

PMID- 24088730
TI  - Clinical characteristics and direct medical cost of respiratory syncytial virus
      infection in children hospitalized in Suzhou, China.
AB  - BACKGROUND: There have been few studies on children hospitalized with respiratory
      syncytial virus (RSV) published from mainland China. We performed a retrospective
      review of medical charts to describe the epidemiology, clinical features and
      direct medical cost of laboratory-proven RSV children hospitalized in Suzhou,
      China. METHODS: Testing is routine for RSV for children admitted to the
      respiratory ward at Suzhou University Children's Hospital. We performed a
      retrospective study on children with documented RSV infection hospitalized at
      Suzhou University Children Hospital during 2005-2009 using a structured chart
      review instrument. RESULTS: A total of 2721 hospitalized children (15.0% of those
      tested) were positive by immunofluorescent assay for RSV during 2005-2009, and
      64.0% of them were male. Eighty-seven percentage of the RSV-infected children
      were 2 years old and younger, and 56.6% were <= 6 months of age. The median
      length of hospital stay was 8 days. Of the RSV-infected children, 92.5% developed
      pneumonia and 21.8% experienced wheezing. In total, 49 (5.1%) of RSV-positive
      children were transferred to the ICU. Children <= 6 months old and who had
      congenital heart disease had higher risk of severe RSV disease. The mean cost of
      each RSV-related hospitalization was US$571.8 (US$909.6 for children referred to
      ICU and US$565.4 for those cared for on the wards). Multivariable logistic
      regression showed that compared with the <= 6 months children, those aged >6
      months old had higher hospitalization cost; children with respiratory distress or
      with chronic lung diseases tended to have higher hospitalization costs than
      others. CONCLUSIONS: RSV infections and severe RSV diseases mostly occurred in
      early infancy. The direct medical cost was high relative to family income.
      Effective strategies of RSV immunization of young children in China may be
      beneficial in addressing this disease burden.

PMID- 24088731
TI  - Two-component Dirac-like Hamiltonian for generating quantum walk on one-, two-
      and three-dimensional lattices.
AB  - From the unitary operator used for implementing two-state discrete-time quantum
      walk on one-, two- and three- dimensional lattice we obtain a two-component Dirac
      like Hamiltonian. In particular, using different pairs of Pauli basis as position
      translation states we obtain three different form of Hamiltonians for evolution
      on one-dimensional lattice. We extend this to two- and three-dimensional lattices
      using different Pauli basis states as position translation states for each
      dimension and show that the external coin operation, which is necessary for one
      dimensional walk is not a necessary requirement for a walk on higher dimensions
      but can serve as an additional resource to control the dynamics. The two
      component Hamiltonian we present here for quantum walk on different lattices can
      serve as a general framework to simulate, control, and study the dynamics of
      quantum systems governed by Dirac-like Hamiltonian. 

PMID- 24088732
TI  - Aerobic and anaerobic contributions to energy production among junior male and
      female cross-country skiers during diagonal skiing.
AB  - PURPOSE: Cross-country-ski races place complex demands on athletes, with events
      lasting between approximately 3 min and 2 h. The aim of the current study was to
      compare the aerobic and anaerobic measures derived from a short time trial (TT)
      between male and female skiers using diagonal cross-country skiing. METHODS:
      Twenty-four highly trained cross-country skiers (12 male and 12 female, age 17.4
      +/- 1.4 y, body mass 68.2 +/- 8.9 kg, height 174 +/- 8 cm) participated. The
      submaximal VO2-speed relationship and VO2max were derived from an incremental
      ramp test to exhaustion (RAMP), while the accumulated oxygen deficit (AOD), peak
      VO2, and performance time were measured during a 600-m TT. RESULTS: The female
      skiers took longer to complete the TT than the males (209 +/- 9 s vs 166 +/- 7 s,
      P < .001) and exhibited a lower relative anaerobic contribution (20% +/- 4% vs
      24% +/- 3%, P = .015) and a higher fractional utilization of VO2max (84% +/- 4%
      vs 79% +/- 5%, P = .007) than males. Although there was no significant difference
      in AOD between the sexes (40.9 +/- 9.5 and 47.3 +/- 7.4 mL/kg for females and
      males, respectively; P = .079), the mean difference +/- 90% confidence intervals
      of 6.4 +/- 6.0 mL/kg reflected a likely practical difference (ES = 0.72). The
      peak VO2 during the TT was significantly higher than VO2max during the RAMP for
      all participants combined (62.3 +/- 6.8 vs 60.5 +/- 7.2 mL . kg-1 . min-1, P =
      .011), and the mean difference +/- 90% confidence intervals of 1.8 +/- 1.1 mL .
      kg-1 . min-1 reflected a possible practical difference (ES = 0.25). CONCLUSIONS:
      These results show that performance and physiological responses to a self-paced
      TT lasting approximately 3 min differ between sexes. In addition, a TT may
      provide a valid measure of VO2max.

PMID- 24088733
TI  - Mortality prediction of nonalcoholic patients presenting with upper
      gastrointestinal bleeding using data mining.
AB  - BACKGROUND AND AIM: Patients with acute upper gastrointestinal (GI) bleeding
      commonly present with hematemesis and/or melena. More studies are needed to
      confirm the ability to predict mortality, length of stay, and cost. Alcohol abuse
      may worsen variceal bleeding or portal hypertensive gastropathy in a patient with
      a history of liver disease. Coexisting alcoholism may influence patient
      management in the setting of peptic ulceration or existing malignancy.
      Consequently, the overall morbidities and mortalities may differ in alcoholic and
      nonalcoholic groups accordingly. Mortality prediction using data mining programs
      is helpful for detection of significant mortality-related factors. PATIENTS AND
      METHODS: We retrospectively reviewed 152 files of patients presenting with upper
      GI bleeding, because of nonalcoholic causes, 100 males and 52 females aged 16-77
      years old. Causes of upper GI bleeding were esophageal and/or gastric varices
      (51), portal hypertensive congestive gastropathy (6), gastric and/or duodenal
      ulcers (39), gastroesophageal reflux disease (20), gastritis and duodenitis (19),
      cancer (8), gastric polyps (3), blood diseases (2), Dieulafoy's lesion (2), and
      no aberrant cause of bleeding in two patients. RESULTS: The overall mortality was
      29 patients (19.07%). The use of a descriptive model of the data mining program
      yielded the most significant mortality predictors. The overall accuracy was
      92.08%. CONCLUSION: Chronic hepatitis C virus infection and NSAID-associated
      splenomegaly because of portal hypertension are significant predictors of
      mortality in nonalcoholic patients presenting with upper GI bleeding.

PMID- 24088735
TI  - Activity of the hypoxia-activated prodrug, TH-302, in preclinical human acute
      myeloid leukemia models.
AB  - PURPOSE: Acute myeloid leukemia (AML) is an aggressive hematologic neoplasm.
      Recent evidence has shown the bone marrow microenvironment in patients with AML
      to be intrinsically hypoxic. Adaptive cellular responses by leukemia cells to
      survive under low oxygenation also confer chemoresistance. We therefore asked
      whether therapeutic exploitation of marrow hypoxia via the hypoxia-activated
      nitrogen mustard prodrug, TH-302, could effectively inhibit AML growth.
      EXPERIMENTAL DESIGN: We assessed the effects of hypoxia and TH-302 on human AML
      cells, primary samples, and systemic xenograft models. RESULTS: We observed that
      human AML cells and primary AML colonies cultured under chronic hypoxia (1% O2,
      72 hours) exhibited reduced sensitivity to cytarabine-induced apoptosis as
      compared with normoxic controls. TH-302 treatment resulted in dose- and hypoxia
      dependent apoptosis and cell death in diverse AML cells. TH-302 preferentially
      decreased proliferation, reduced HIF-1alpha expression, induced cell-cycle
      arrest, and enhanced double-stranded DNA breaks in hypoxic AML cells. Hypoxia
      induced reactive oxygen species by AML cells were also diminished. In systemic
      human AML xenografts (HEL, HL60), TH-302 [50 mg/kg intraperitoneally (i.p.) 5
      times per week] inhibited disease progression and prolonged overall survival. TH
      302 treatment reduced the number of hypoxic cells within leukemic bone marrows
      and was not associated with hematologic toxicities in nonleukemic or leukemic
      mice. Later initiation of TH-302 treatment in advanced AML disease was as
      effective as earlier TH-302 treatment in xenograft models. CONCLUSIONS: Our
      results establish the preclinical activity of TH-302 in AML and provide the
      rationale for further clinical studies of this and other hypoxia-activated agents
      for leukemia therapy.

PMID- 24088734
TI  - Quantification of excision repair cross-complementing group 1 and survival in p16
      negative squamous cell head and neck cancers.
AB  - PURPOSE: Multimodality treatment of squamous cell carcinoma of the head and neck
      (SCCHN) often involves radiotherapy and cisplatin-based therapy. Elevated
      activity of DNA repair mechanisms, such as the nucleotide excision repair (NER)
      pathway, of which ERCC1 is a rate-limiting element, are associated with cisplatin
      and possibly RT resistance. We have determined excision repair cross
      complementing group 1 (ERCC1) expression in human papillomavirus (HPV)-negative
      SCCHN treated with surgery [+/- adjuvant radiotherapy/chemoradiation (CRT)].
      EXPERIMENTAL DESIGN: We assessed ERCC1 protein expression in archival tumors
      using immunofluorescence staining and automatic quantitative analysis (AQUA) with
      three antibodies to ERCC1 (8F1, FL297, and HPA029773). Analysis with
      Classification and Regression Tree (CART) methods ascertained the cutoff points
      between high/low ERCC1 expression. Multivariable analysis adjusted for age, T,
      and N stage. Kaplan-Meier curves determined median survival. ERCC1 expression at
      initial tumor presentation and in recurrent disease were compared. Performance
      characteristics of antibodies were assessed. RESULTS: ERCC1 low/high groups were
      defined on the basis of AQUA analysis with 8F1/2009, FL297, and HPA029773. Among
      patients treated with surgery plus adjuvant radiotherapy/CRT, longer median
      survival was observed in ERCC1-low versus ERCC1-high tumors (64 vs. 29 months; P
      = 0.02; HPA029773). Data obtained with HPA029773 indicated no survival difference
      among patients treated only with surgery. Recurrent cancers had lower ERCC1 AQUA
      scores than tumors from initial presentation. Extensive characterization
      indicated optimal specificity and performance by the HPA029773 antibody.
      CONCLUSIONS: Using AQUA, with the specific ERCC1 antibody HPA029773, we found a
      statistical difference in survival among high/low-ERCC1 tumors from patients
      treated with surgery and adjuvant radiotherapy.

PMID- 24088736
TI  - Photodynamic therapy with 3-(1'-hexyloxyethyl) pyropheophorbide a for cancer of
      the oral cavity.
AB  - PURPOSE: The primary objective was to evaluate safety of 3-(1'
      hexyloxyethyl)pyropheophorbide-a (HPPH) photodynamic therapy (HPPH-PDT) for
      dysplasia and early squamous cell carcinoma of the head and neck (HNSCC).
      Secondary objectives were the assessment of treatment response and reporters for
      an effective PDT reaction. EXPERIMENTAL DESIGN: Patients with histologically
      proven oral dysplasia, carcinoma in situ, or early-stage HNSCC were enrolled in
      two sequentially conducted dose escalation studies with an expanded cohort at the
      highest dose level. These studies used an HPPH dose of 4 mg/m(2) and light doses
      from 50 to 140 J/cm(2). Pathologic tumor responses were assessed at 3 months.
      Clinical follow up range was 5 to 40 months. PDT induced cross-linking of STAT3
      were assessed as potential indicators of PDT effective reaction. RESULTS: Forty
      patients received HPPH-PDT. Common adverse events were pain and treatment site
      edema. Biopsy proven complete response rates were 46% for dysplasia and carcinoma
      in situ and 82% for squamous cell carcinomas (SCC) lesions at 140 J/cm(2). The
      responses in the carcinoma in situ/dysplasia cohort are not durable. The PDT
      induced STAT3 cross-links is significantly higher (P = 0.0033) in SCC than in
      carcinoma in situ/dysplasia for all light doses. CONCLUSION: HPPH-PDT is safe for
      the treatment of carcinoma in situ/dysplasia and early-stage cancer of the oral
      cavity. Early-stage oral HNSCC seems to respond better to HPPH-PDT in comparison
      with premalignant lesions. The degree of STAT3 cross-linking is a significant
      reporter to evaluate HPPH-PDT-mediated photoreaction.

PMID- 24088739
TI  - Control of chemical reactions and synthesis by low-energy electrons.
AB  - Controlling the outcome of reactions is a central issue of chemical research.
      Physical tools can achieve this if they are able to precisely dissociate specific
      bonds of a molecule. However, to control synthesis, such tools must induce the
      formation of new bonds between two reactants to yield a more complex product. In
      the ideal case of an atom efficient synthesis, this product would contain all or
      at least most of the initial material. An electron beam is a physical tool that
      is capable of preparing molecules in reactive states or, at low electron
      energies, of initiating highly selective bond dissociation. The resulting
      fragments in turn can react with other molecules to yield stable products. This
      tutorial review focuses in particular on such low-energy electron-initiated
      molecular syntheses and their applications in the modification of surfaces. It
      thus emphasizes strategies towards the controlled and predictable formation of
      more complex products from small reactants initiated by interaction with low
      energy electrons either through selective bond dissociation or formation of
      specific reactive molecular species. However, selective bond dissociation is not
      always desirable. This is briefly illustrated by the case of electron beam
      induced deposition where additional strategies may be required to control product
      formation. 

PMID- 24088737
TI  - Novel methylation biomarker panel for the early detection of pancreatic cancer.
AB  - PURPOSE: Pancreatic cancer is the fourth leading cause of cancer deaths and there
      currently is no reliable modality for the early detection of this disease. Here,
      we identify cancer-specific promoter DNA methylation of BNC1 and ADAMTS1 as a
      promising biomarker detection strategy meriting investigation in pancreatic
      cancer. EXPERIMENTAL DESIGN: We used a genome-wide pharmacologic transcriptome
      approach to identify novel cancer-specific DNA methylation alterations in
      pancreatic cancer cell lines. Of eight promising genes, we focused our studies on
      BNC1 and ADAMTS1 for further downstream analysis, including methylation and
      expression. We used a nanoparticle-enabled methylation on beads (MOB) technology
      to detect early-stage pancreatic cancers by analyzing DNA methylation in patient
      serum. RESULTS: We identified two novel genes, BNC1 (92%) and ADAMTS1 (68%), that
      showed a high frequency of methylation in pancreatic cancers (n = 143), up to
      100% in PanIN-3 and 97% in stage I invasive cancers. Using the nanoparticle
      enabled MOB technology, these alterations could be detected in serum samples (n =
      42) from patients with pancreatic cancer, with a sensitivity for BNC1 of 79% [95%
      confidence interval (CI), 66%-91%] and for ADAMTS1 of 48% (95% CI, 33%-63%),
      whereas specificity was 89% for BNC1 (95% CI, 76%-100%) and 92% for ADAMTS1 (95%
      CI, 82%-100%). Overall sensitivity using both markers is 81% (95% CI, 69%-93%)
      and specificity is 85% (95% CI, 71%-99%). CONCLUSIONS: Promoter DNA methylation
      of BNC1 and ADAMTS1 is a potential biomarker to detect early-stage pancreatic
      cancers. Assaying the promoter methylation status of these genes in circulating
      DNA from serum is a promising strategy for early detection of pancreatic cancer
      and has the potential to improve mortality from this disease.

PMID- 24088738
TI  - A phase II and biomarker study of ramucirumab, a human monoclonal antibody
      targeting the VEGF receptor-2, as first-line monotherapy in patients with
      advanced hepatocellular cancer.
AB  - PURPOSE: To assess the efficacy and safety of the anti-VEGF receptor-2 (VEGFR-2)
      antibody ramucirumab as first-line therapy in patients with advanced
      hepatocellular carcinoma and explore potential circulating biomarkers.
      EXPERIMENTAL DESIGN: Adults with advanced hepatocellular carcinoma and no prior
      systemic treatment received ramucirumab 8 mg/kg every two weeks until disease
      progression or limiting toxicity. The primary endpoint was progression-free
      survival (PFS); secondary endpoints included objective response rate (ORR) and
      overall survival (OS). Circulating biomarkers were evaluated before and after
      ramucirumab treatment in a subset of patients. RESULTS: Forty-two patients
      received ramucirumab. Median PFS was 4.0 months [95% confidence interval (CI),
      2.6-5.7], ORR was 9.5% (95% CI, 2.7-22.6; 4/42 patients had a partial response),
      and median OS was 12.0 months (95% CI, 6.1-19.7). For patients with Barcelona
      Clinic Liver Cancer (BCLC) stage C disease, median OS was 4.4 months (95% CI, 0.5
      9.0) for patients with Child-Pugh B cirrhosis versus 18.0 months (95% CI, 6.1
      23.5) for patients with Child-Pugh A cirrhosis. Treatment-related grade >= 3
      toxicities included hypertension (14%), gastrointestinal hemorrhage and infusion
      related reactions (7% each), and fatigue (5%). There was one treatment-related
      death (gastrointestinal hemorrhage). After treatment with ramucirumab, there was
      an increase in serum VEGF and placental growth factor (PlGF) and a transient
      decrease in soluble VEGFR-2. CONCLUSION: Ramucirumab monotherapy may confer
      anticancer activity in advanced hepatocellular carcinoma with an acceptable
      safety profile. Exploratory biomarker studies showed changes in circulating VEGF,
      PlGF, and sVEGFR-2 that are consistent with those seen with other anti-VEGF
      agents.

PMID- 24088740
TI  - Griffiths phases and the stretching of criticality in brain networks.
AB  - Hallmarks of criticality, such as power-laws and scale invariance, have been
      empirically found in cortical-network dynamics and it has been conjectured that
      operating at criticality entails functional advantages, such as optimal
      computational capabilities, memory and large dynamical ranges. As critical
      behaviour requires a high degree of fine tuning to emerge, some type of self
      tuning mechanism needs to be invoked. Here we show that, taking into account the
      complex hierarchical-modular architecture of cortical networks, the singular
      critical point is replaced by an extended critical-like region that corresponds-
      in the jargon of statistical mechanics--to a Griffiths phase. Using computational
      and analytical approaches, we find Griffiths phases in synthetic hierarchical
      networks and also in empirical brain networks such as the human connectome and
      that of Caenorhabditis elegans. Stretched critical regions, stemming from
      structural disorder, yield enhanced functionality in a generic way, facilitating
      the task of self-organizing, adaptive and evolutionary mechanisms selecting for
      criticality.

PMID- 24088741
TI  - A facile approach for in situ synthesis of graphene-branched-Pt hybrid
      nanostructures with excellent electrochemical performance.
AB  - A facile and green approach for the synthesis of highly electroactive branched Pt
      nanostructures well dispersed on graphene has been developed by in situ reduction
      of graphene oxides and Pt(iv) ions in an aqueous medium. The as-synthesized
      branched Pt and graphene hybrid nanomaterials (GR-BPtNs) were thoroughly
      characterized using Transmission Electron Microscope (TEM), UV-Visible
      spectroscopy, Fourier transform infrared spectroscopy (FT-IR), thermogravimetric
      analysis (TGA) and Raman spectroscopy. This report clearly exploits the decisive
      role of the graphene support, the pH of the solution and the stabiliser on
      shaping the branched morphology of the Pt nanostructures well dispersed on
      graphene. Cyclic voltammetry, chronoamperometry and electrochemical impedance
      spectroscopy (EIS) measurements were employed to investigate the electrocatalytic
      performance and durability of GR-BPtNs towards methanol oxidation and oxygen
      reduction. The results reveal that the synergetic effect of the graphene support
      and the branched morphology triggers electrocatalytic performance and robust
      tolerance to surface poisoning of GR-BPtNs. 

PMID- 24088742
TI  - Quest for a highly connected robust porous metal-organic framework on the basis
      of a bifunctional linear linker and a rare heptanuclear zinc cluster.
AB  - A strategy for building highly connected robust MOFs from linear ligands is
      exemplified by the construction of MTAF-4, a rare (6,9)-connected MOF, based on
      the custom-designed bifunctional linear ligand, 4-(1,2,3-triazol-4-yl)-benzoate,
      that connects two types of highly connected zinc cluster moieties generated in
      situ. MTAF-4 is robust and permanently microporous and is capable of adsorbing
      CO2, H2 and CH4 under high pressures. 

PMID- 24088743
TI  - Nuclear organization: Processing at the pore.

PMID- 24088744
TI  - To be or not to be assembled: progressing into nuclear actin filaments.
AB  - The paradigm states that cytoplasmic actin operates as filaments and nuclear
      actin is mainly monomeric, acting as a scaffold in transcription complexes.
      However, why should a powerful function of actin, namely polymerization, not be
      used in the nucleus? Recent progress in the field forces us to rethink this
      issue, as many actin filament assembly proteins have been linked to nuclear
      functions and new experimental approaches have provided the first direct
      visualizations of polymerized nuclear actin. 

PMID- 24088745
TI  - CRISPR/Cas9-mediated genome engineering and the promise of designer flies on
      demand.
AB  - The CRISPR/Cas9 system has attracted significant attention for its potential to
      transform genome engineering. We and others have recently shown that the RNA
      guided Cas9 nuclease can be employed to engineer the Drosophila genome, and that
      these modifications are efficiently transmitted through the germline. A single
      targeting RNA can guide Cas9 to a specific genomic sequence where it induces
      double-strand breaks that, when imperfectly repaired, yield mutations. We have
      also demonstrated that 2 targeting RNAs can be used to generate large defined
      deletions and that Cas9 can catalyze gene replacement by homologous
      recombination. Zinc-finger nucleases (ZFNs) and transcription activator-like
      effector nucleases (TALENs) have shown similar promise in Drosophila. However,
      the ease of producing targeting RNAs over the generation of unique sequence
      directed nucleases to guide site-specific modifications makes the CRISPR/Cas9
      system an appealingly accessible method for genome editing. From the initial
      planning stages, engineered flies can be obtained within a month. Here we
      highlight the variety of genome modifications facilitated by the CRISPR/Cas9
      system along with key considerations for starting your own CRISPR genome
      engineering project. 

PMID- 24088747
TI  - High prevalence of cyclical variation in heart rate before nocturnal episodes of
      paroxysmal atrial fibrillation.
AB  - OBJECTIVE: Nighttime onset of atrial fibrillation (AF) is sometimes associated
      with obstructive sleep apnea accompanied by a characteristic heart rate (HR)
      pattern known as cyclical variation of HR. The aim of this study was to evaluate
      whether cyclical variation of HR is prevalent in patients with nocturnal AF.
      METHODS: The subjects consisted of 34 patients (68+/-12 years) with paroxysmal
      AF, including 14 patients with daytime AF and 20 patients with nighttime AF.
      Holter electrocardiogram (ECGs) were examined for the presence of cyclical
      variation in HR and to quantify the HR variability within the 40-minute period
      preceding each AF episode using a fast Fourier transform (FFT) methods. RESULTS:
      Cyclical variation in HR was observed in 12 of 20 (60%) nighttime episodes and in
      only two of 14 (14%) daytime episodes. The prevalence of cyclical variation in HR
      was significantly greater in the nighttime AF episodes than in the daytime AF
      episodes (Chi=5.34, p<0.05). The mean frequency of cyclical variation in HR was
      0.015+/-0.003 Hz. The mean power of the VLF (very low frequency) component (0.008
      0.04 Hz) before the onset of AF was significantly greater in the nighttime AF
      episodes than in the daytime AF episodes. Among the nighttime AF episodes, the
      power of the HF (high frequency), LF (low frequency) and very low frequency (VLF)
      components increased significantly just before the onset of AF compared with that
      observed 40 minutes before onset. CONCLUSION: The high prevalence of cyclical
      variation in HR observed before nocturnal AF episodes suggests that sleep apnea
      may play a role in the onset of nighttime AF.

PMID- 24088746
TI  - Amputation and prosthesis implantation shape body and peripersonal space
      representations.
AB  - Little is known about whether and how multimodal representations of the body
      (BRs) and of the space around the body (Peripersonal Space, PPS) adapt to
      amputation and prosthesis implantation. In order to investigate this issue, we
      tested BR in a group of upper limb amputees by means of a tactile distance
      perception task and PPS by means of an audio-tactile interaction task. Subjects
      performed the tasks with stimulation either on the healthy limb or the stump of
      the amputated limb, while wearing or not wearing their prosthesis. When patients
      performed the tasks on the amputated limb, without the prosthesis, the perception
      of arm length shrank, with a concurrent shift of PPS boundaries towards the
      stump. Conversely, wearing the prosthesis increased the perceived length of the
      stump and extended the PPS boundaries so as to include the prosthetic hand, such
      that the prosthesis partially replaced the missing limb. 

PMID- 24088748
TI  - The levels of the circulating cellular adhesion molecules ICAM-1, VCAM-1 and
      endothelin-1 and the flow-mediated vasodilatation values in patients with type 1
      diabetes mellitus with early-stage diabetic retinopathy.
AB  - OBJECTIVE: Endothelial dysfunction plays an important role in the development of
      diabetic retinopathy. The aim of this study was to evaluate endothelial
      dysfunction using different approaches in patients with type 1 diabete mellitus
      with early stages of diabetic retinopathy. For this purpose, we investigated the
      serum levels of cellular adhesion molecules, including intercellular adhesion
      molecule (ICAM-1), vascular cell adhesion molecule (VCAM-1) and endothelin-1 (ET
      1), which have emerged as specific markers of endothelial dysfunction, and
      measured the flow-mediated dilatation (FMD), a noninvasive technique used to
      evaluate endothelial dysfunction. METHODS: The study group included 59 patients
      with type 1 diabetes mellitus (DM) and 30 age-matched healthy control subjects.
      The diabetic patients were divided into two groups according to the
      ophthalmoscopic findings: Group 1, composed of type 1 diabetic patients having no
      signs of diabetic retinopathy (DRP), and Group 2, composed of type 1 diabetic
      patients having findings of the early stages of nonproliferative diabetic
      retinopathy (NPDR). RESULTS: The serum levels of ET-1 (fmol/mL), ICAM-1 (ng/mL)
      and VCAM-1 (ng/mL) were 8.52+/-0.699 vs. 478.39+/-46.22 vs. 728.64+/-35.081 in
      the patients without retinopathy, 8.91+/-1.354 vs. 451.79+/-48.262 vs. 863.59+/
      62.37 in the diabetic patients with NPDR and 10.73+/-1.04 vs. 608.15+/-74.92 vs.
      872.95+/-57.63 in the control group. There were no significant differences in the
      serum levels of the three molecules between the groups. The FMD values were
      6.51+/-0.46% in the diabetic patients without retinopathy, 6.66+/-0.29% in the
      diabetic patients with NPDR and 6.68+/-0.51% in the control group. No significant
      differences were found between the groups. CONCLUSION: The early stages of
      diabetic retinopathy cannot be considered in the evaluation of systemic markers
      of endothelial dysfunction.

PMID- 24088750
TI  - Spontaneous pneumothorax with persistent air leakage and invasive procedures.
AB  - OBJECTIVE: Prolonged air leaks in patients with spontaneous pneumothorax are not
      infrequent. The aim of this study was to assess the duration of air leaks and
      define the clinical variables associated with the therapeutic success of chest
      tube drainage for spontaneous pneumothorax. METHODS: A total of 441 patients with
      spontaneous pneumothorax treated with chest tube drainage between 2008 and 2012
      were retrospectively evaluated. The clinical differences between the patients
      successfully treated with drainage and those who required more invasive
      procedures were analyzed. RESULTS: Invasive procedures, such as video-assisted
      thoracic surgery (n=121), fibrin glue administration through a chest tube (n=8)
      and pleurodesis with OK-432 (n=21), were performed in 34% (150/441) of the
      patients. The treatment rate of chest drainage alone was higher in the patients
      with initial pneumothorax (72%; 124/170) than in those with recurrent
      pneumothorax (62%; 167/271) (p=0.015). In addition, this rate was higher in the
      patients with moderate lung collapse (70%; 167/237) than in those with severe
      lung collapse (61%; 124/204) (p=0.032). CONCLUSION: Patients with recurrent
      pneumothorax or severe lung collapse associated with prolonged air leakage are
      more likely to receive invasive procedures.

PMID- 24088749
TI  - Variations in inflammatory biomarkers following the addition of sitagliptin in
      patients with type 2 diabetes not controlled with metformin.
AB  - OBJECTIVE: The effects of dipeptidyl peptidase-4 (DPP-4) inhibition on adipose
      tissue inflammation remain obscure. The aim of this study was to evaluate the
      effects of the addition of sitagliptin on the beta-cell function and various
      inflammatory biomarkers in type 2 diabetic patients. METHODS: After a run-in
      period of taking metformin, 178 diabetic patients with poor glycemic control were
      randomized to take sitagliptin at a dose of 100 mg once a day or a placebo in
      addition to metformin for 12 months. We evaluated the following parameters at
      three, six, nine and twelve months: body mass index (BMI), glycemic control, the
      homeostasis model assessment insulin resistance index (HOMA-IR), the homeostasis
      model assessment beta-cell function index (HOMA-beta), the proinsulin/fasting
      plasma insulin ratio (Pr/FPI ratio) and the levels of fasting plasma insulin
      (FPI), fasting plasma proinsulin (FPPr), C-peptide, glucagon, resistin, vaspin,
      omentin-1 and tumor necrosis factor-alpha (TNF-alpha). Before and twelve months
      after the addition of sitagliptin, the patients underwent combined euglycemic
      hyperinsulinemic and hyperglycemic clamping with subsequent arginine stimulation
      to assess insulin sensitivity and secretion. RESULTS: Treatment with sitagliptin
      + metformin was more effective than placebo + metformin in improving glycemic
      control, the HOMA-IR and the glucagon level and increasing the HOMA-beta and all
      beta-cell measurements after combined euglycemic hyperinsulinemic and
      hyperglycemic clamping with subsequent arginine stimulation. Regarding
      inflammatory biomarkers, sitagliptin + metformin more effectively reduced the
      levels of resistin, vaspin and omentin-1 than placebo + metformin. CONCLUSION:
      When treatment with metformin alone is not adequate for obtaining glycemic
      control, the addition of sitagliptin can be considered due to its actions in
      preserving the beta-cell function and reducing the levels of biomarkers of
      inflammation.

PMID- 24088751
TI  - Association between acute myelogenous leukemia and thrombopoietin receptor
      agonists in patients with immune thrombocytopenia.
AB  - OBJECTIVE: The development of myeloid malignancies is a concern when
      administering thrombopoietin receptor (or the myeloproliferative leukemia virus
      proto-oncogene product, MPL) agonists. Progression from myelodysplastic syndrome
      (MDS) to acute myelogenous leukemia [AML, 9 (6.12%) AML patients among 147 MDS
      subjects] was reported in a clinical trial. However, only one (0.15%) case of AML
      among 653 immune thrombocytopenic purpura (ITP) subjects was reported. Our
      objective was to determine whether there is currently a safety signal in the FDA
      files termed Food and Drug Administration (FDA) Adverse Event Reporting System
      (FAERS) for AML in ITP patients who receive MPL agonists. METHODS: We conducted a
      case-controlled study using the FAERS as a source of case and control data. We
      compared demographic characteristics, such as gender, age and exposure to MPL
      agonists between AML patients and others among ITP subjects registered between
      2002 and 2011. RESULTS: Total of 4,821 ITP subjects were identified, including 62
      AML patients. The number of patients treated with romiplostim and eltrombopag was
      54 (1.74%) AML patients among 3,102 ITP subjects and nine (1.52%) AML patients
      among 594 ITP subjects, respectively. It should be noted that all AML patients
      were exposed to one or more MPL agonists. Another factor associated with AML was
      male gender. CONCLUSION: We herein report an association between AML and MPL
      agonist use in ITP subjects. Due to various biases and the incompleteness of the
      FAERS data, further studies are warranted to determine whether the detected
      signal is a real risk. Physicians should not alter their prescribing behaviors
      based on this single preliminary analysis.

PMID- 24088752
TI  - Cerebrospinal fluid neopterin, but not osteopontin, is a valuable biomarker for
      the treatment response in patients with HTLV-I-associated myelopathy.
AB  - OBJECTIVE: The concentrations of neopterin and osteopontin in the cerebrospinal
      fluid (CSF) were measured in patients with HTLV-I-associated myelopathy/tropical
      spastic paraparesis (HAM/TSP) in order to evaluate their utility as biomarkers
      for the treatment response. METHODS: Seven HAM/TSP patients were treated
      intravenously with high-dose methylprednisolone (1,000 mg/day) for 3 days. CSF
      samples were collected before and after the treatment. The neopterin and
      osteopontin concentrations were determined using high-performance liquid
      chromatography (HPLC) and an enzyme immunoassay, respectively. The clinical
      symptoms were evaluated using the Osame Motor Disability Score and the Urinary
      Disturbance Score. RESULTS: Four out of the seven patients showed an improvement
      in motor function with the treatment, and were therefore classed as responders.
      The pre-treatment CSF neopterin concentration exceeded the upper limit of normal
      in all seven of the patients, and tended to be higher in treatment responders as
      compared to non-responders. The CSF neopterin concentration was reduced following
      treatment in all patients. The mean CSF neopterin concentration significantly
      (p<0.01) decreased following treatment by almost 60% (from 124.1+/-79.9 nmol/L to
      49.2+/-29.8 nmol/L). The mean CSF osteopontin concentration was significantly
      (p<0.01) higher in the HAM/TSP patients in comparison to the 18 HTLV-1
      seronegative patients who were designated as controls (9.54+/-4.53 mg/L vs.
      3.72+/-3.04 mg/L). No significant (p=0.47) reduction of the CSF osteopontin
      concentration was observed following the intravenous administration of high-dose
      methylprednisolone. CONCLUSION: These results indicate that the CSF neopterin
      concentration, but not the osteopontin concentration, is a potentially valuable
      biomarker for monitoring the treatment response in HAM/TSP patients. Furthermore,
      high pre-treatment CSF neopterin concentrations may be a predictive biomarker for
      a response to intravenous high-dose methylprednisolone therapy.

PMID- 24088753
TI  - Risk factors for liver injury with an elevated serum bilirubin concentration
      caused by antituberculous drugs.
AB  - OBJECTIVE: No studies have so far sufficiently investigated the risk factors for
      drug-induced liver injury (DILI) with an elevated serum bilirubin concentration.
      METHODS: We conducted a historical cohort study observing inpatients admitted to
      two hospitals in Japan. A decreased level of activities of daily living (ADL) was
      defined as a Barthel Index score of <80. The patients were treated with standard
      regimens under a directly observed treatment short-course strategy. RESULTS: The
      cohort of 356 patients comprised 244 men (68.5%) and 112 women (31.5%), with a
      mean age of 63.8+/-20.2 years. Compared with the patients who did not experience
      DILI with a bilirubin level of >=2.0 mg/dL, the patients who experienced DILI
      with a bilirubin level of >=2.0 mg/dL more often had a decreased level of ADLs,
      were more likely to suffer from chronic cardiac disease, had lower serum albumin
      levels and were less often treated with four-drug regimens involving pyrazinamide
      (PZA). In a logistic regression analysis in which these five factors acted as
      independent variables, a decreased level of ADLs was the strongest predictor for
      DILI with a bilirubin level of >=2.0 mg/dL, with an odds ratio of 16.5 (95%CI:
      1.7-159; p=0.015), followed by chronic cardiac disease, with an odds ratio of 4.0
      (95%CI: 1.2-12.6; p=0.020). CONCLUSION: A decreased level of ADLs and chronic
      cardiac disease are strong risk factors for DILI with a bilirubin level of >=2.0
      mg/dL resulting from the use of antituberculous drugs. Physicians should pay
      close attention to the possibility of DILI with a bilirubin level of >=2.0 mg/dL
      when treating tuberculosis patients with a decreased level of ADLs and/or chronic
      heart disease.

PMID- 24088754
TI  - Cap-polyposis-like gastropathy with hypoproteinemia treated with H. pylori
      eradication.
AB  - We herein report the case of a 43-year-old man with distinct gastropathy and
      hypoproteinemia treated with H. pylori eradication therapy. Most reported cases
      of protein-losing gastropathy are divided into Menetrier's disease (MD) and
      diffuse varioliform gastritis (DVG). Our patient presented with leg edema due to
      marked hypoalbuminemia, which we ascribed to distinct gastropathy with novel
      endoscopic findings resembling cap polyposis in the colon, apparently different
      from both MD and DVG. H. pylori eradication therapy promptly induced the
      normalization of laboratory data and mucosal healing. Our case together with two
      previously published similar cases may contribute to establishing an association
      between cap-polyposis-like-gastropathy with hypoproteinemia and H. pylori. 

PMID- 24088755
TI  - Hepatic xanthoma associated with pasireotide administration: a first case report.
AB  - Hepatic xanthoma is an extremely rare lesion worldwide. We herein present a case
      of hepatic xanthoma that developed in a 27-year-old Taiwanese man who had
      participated in a clinical trial of pasireotide. This is, to the best of our
      knowledge, the first case of pasireotide-induced hepatic xanthoma. Following
      discontinuation of the drug, the tumor continued to decrease in size (98.2%
      decrease in tumor volume). We suggest that, in patients receiving pasireotide,
      the liver should be checked using periodic radiological examinations, even if the
      patient does not exhibit any risk factors, and that medical or surgical
      intervention may not be needed. 

PMID- 24088756
TI  - Multiple hypervascular FNH-like lesions in a patient with no history of alcohol
      abuse or chronic liver disease.
AB  - A 64-year-old Japanese woman with a history of bronchiectasis presented with
      multiple hypervascular nodules in both lobes of the liver without hepatitis B or
      C virus infection. Imaging studies, including ultrasound, contrast-enhanced
      computed tomography and magnetic resonance imaging, showed hypervascularity in
      the early phase. Histologically, no lipid degeneration was observed; however,
      there was a mild increase in cell density, miniaturization of nuclei, increased
      chromatin content, partial sinusoidal dilatation and congestion. No unpaired
      arteries were evident. The diagnosis based on the pathology and diagnostic
      radiology findings was multiple hypervascular focal nodular hyperplasia (FNH)
      like lesions with no history of alcohol abuse or chronic liver disease. 

PMID- 24088757
TI  - Purulent pericarditis and cardiac tamponade caused by Nocardia farcinica in a
      nephrotic syndrome patient.
AB  - Nocardiosis is an uncommon infection that occurs primarily in immunocompromised
      patients. We herein report an extremely rare case of Nocardia farcinica (N.
      farcinica) pericarditis. A 53-year-old man with nephrotic syndrome that required
      chronic corticosteroid therapy presented with pleuritic chest pain and cardiac
      tamponade. Pericardiocentesis revealed purulent pericardial effusion and a
      bacteriological examination showed the characteristic branching filamentous
      bacteria identified as N. farcinica. Aggressive surgical drainage and a
      trimethoprim-sulfamethoxazole based regimen resulted in clinical improvement. To
      the best of our knowledge, this is the first reported case of N. farcinica
      pericarditis in Thailand. 

PMID- 24088758
TI  - Risk of stroke due to spontaneous cervical artery dissection.
AB  - Although spontaneous cervical artery dissection (SCAD) is generally a rare
      contributor to a stroke, this condition triggers a considerable percentage of the
      strokes that are observed in young to middle-aged patients. We herein report the
      findings of a patient who presented with a stroke and a severe headache. A
      diagnosis of SCAD was made following a series of examinations. The patient had
      high-grade stenosis in the cervical artery and received carotid angioplasty along
      with stenting. A diagnosis of SCAD should be suspected if a patient who is less
      than 50 years of age presents with a stroke and a severe headache, and CT or an
      MRI scan rules out hemorrhage. 

PMID- 24088759
TI  - Effects of continuous positive airway pressure therapy in three Japanese patients
      with obstructive sleep apnea and resistant hypertension.
AB  - The following three case reports present the effects of 6-month continuous
      positive airway pressure (CPAP) therapy on blood pressure (BP) in severe
      obstructive sleep apnea patients with resistant hypertension. Case 1 A 58-year
      old woman exhibited a decreased 24-hour BP and changes in the nocturnal BP
      dipping pattern from non-dipper to dipper. Case 2 A 64-year-old man showed no
      improvements in nocturnal BP. Case 3 A 78-year-old man with ischemic
      cardiomyopathy exhibited changes in the nocturnal BP dipping pattern from non
      dipper to dipper. These results suggest that 6-month CPAP therapy improves the
      nocturnal BP dipping status in some patients with obstructive sleep apnea and
      resistant hypertension. 

PMID- 24088760
TI  - Severe lactic acidosis and acute pancreatitis associated with cimetidine in a
      patient with type 2 diabetes mellitus taking metformin.
AB  - An 82-year-old woman with type 2 diabetes mellitus, hypertension, and unstable
      angina presented with severe lactic acidosis and acute kidney injury (AKI)
      accompanied by acute pancreatitis. Her medical history revealed that she had
      taken cimetidine for two weeks while taking other medications, including
      metformin. Continuous veno-venous hemodiafiltration (CVVHDF) was initiated under
      diagnosis of lactic acidosis due to metformin and AKI caused by cimetidine
      induced acute pancreatitis. In three days of CVVHDF, the levels of serum
      biochemical markers of lactic acidosis and AKI improved and the patient's urine
      output reached over 1 L/day. The pancreatitis improved over time. 

PMID- 24088761
TI  - Small-cell lung cancer exhibiting spontaneous regression.
AB  - A 56-year-old woman was admitted to our hospital because a chest X-ray and
      thoracic computed tomography (CT) scan revealed a heterogeneous tumor in the
      middle mediastinum during a visit to a nearby clinic for a consultation regarding
      a persistent cough and body weight loss. However, the tumor spontaneously
      decreased on thoracic CT performed on admission. Subsequently, a biopsy of the
      tumor using video-assisted thoracoscopy was performed. The pathological findings
      disclosed the tumor to be small-cell lung cancer with infiltration of CD8
      positive T-cells exhibiting spontaneous regression. Cell-mediated immunity,
      including CD8-positive T-cells, may have relevance to the spontaneous regression
      of malignant tumors. 

PMID- 24088762
TI  - Antineutrophil cytoplasmic antibody-associated vasculitis involving diffuse
      alveolar hemorrhage, rapidly progressive glomerulonephritis and
      hypereosinophilia.
AB  - The classification of antineutrophil cytoplasmic antibody (ANCA)-associated
      vasculitis (AAV) has limitations because the condition includes disorders with
      similar general clinical features, similar characteristics of lung and renal
      involvement and a positive ANCA serology. A 40-year-old woman was admitted to our
      hospital for hemoptysis and dyspnea. She had no history of bronchial asthma.
      Laboratory examinations revealed hypereosinophilia, positive anti-myeloperoxidase
      antibodies, hematuria and proteinuria. The patient was ultimately diagnosed with
      AAV associated with diffuse alveolar hemorrhage, rapidly progressive
      glomerulonephritis and hypereosinophilia without bronchial asthma. Obtaining a
      definitive diagnosis of ANCA vasculitis can be very difficult, and the
      characteristics of this case were not compatible with the findings of typical
      AVV. We herein report a rare case of AVV. 

PMID- 24088763
TI  - Long-term remission achieved via combined chemotherapy and radiotherapy in a non
      resectable granulocyte colony-stimulating factor producing pleomorphic carcinoma
      of the lung.
AB  - The prognosis is poor for patients with advanced pleomorphic carcinoma of the
      lung due to the generally limited response to chemotherapy and/or radiotherapy.
      It has been suggested the production of granulocyte colony-stimulating factor (G
      CSF) by cancer cells may aggravate the disease progression. We herein report a
      case of a 73-year-old Japanese man with advanced G-CSF-producing pleomorphic
      carcinoma of the lung. First-line chemotherapy with carboplatin and paclitaxel
      had been suspended. Subsequent radiotherapy achieved a moderate volume reduction
      and an amelioration of the excessive G-CSF-related complications. Six cycles of
      second-line chemotherapy with docetaxel administered with good results. These
      combined treatments resulted in long term survival without progression of the
      disease. 

PMID- 24088764
TI  - Immune reconstitution inflammatory syndrome mimics a relapse of AIDS-related
      Burkitt lymphoma.
AB  - Immune reconstitution inflammatory syndrome (IRIS) is associated with clinical
      manifestations that can overlap with the patients with acquired immunodeficiency
      disease (AIDS)-related non-Hodgkin's lymphoma. We herein report a case of AIDS
      related Burkitt lymphoma which was successfully treated with dose-adjusted
      etoposide, doxorubicin, cyclophosphamide, vincristine, and prednisone (EPOCH).
      However, the patient developed a lymphoma-like clinical presentation shortly
      after the conclusion of chemotherapy. The patient's symptoms were identical to
      the initial symptoms characteristic of lymphoma; however, the laboratory data
      revealed no evidence of a relapse of Burkitt lymphoma. A bone marrow examination
      showed T-cell clonality, even though there were no signs of any progression of
      the lymphoma. The patient was diagnosed with IRIS, and the clinical
      manifestations rapidly improved following treatment. 

PMID- 24088765
TI  - Neuronal ceroid lipofuscinosis with early-onset dementia and periventricular
      leukoencephalopathy in which a skin biopsy was diagnostically useful.
AB  - Neuronal ceroid lipofuscinosis (NCL) is a rare disease with onset typically
      during childhood; however, that developing during adulthood can lead to early
      onset dementia. We report a 54-year-old man whose onset coincided with speech
      impairment, amnesia and dyscalculia. On brain MRI, marked diffuse
      leukoencephalopathy with periventricular predominance was observed. On a skin
      biopsy, characteristic fingerprint images were noted, and the patient was
      diagnosed with NCL. The differential diagnosis of cognitive impairment with
      leukoencephalopathy is wide ranging; however, when marked symmetrical
      periventricular-predominant leukoencephalopathy is prevalent and no peripheral
      neuropathy or gait disorders are evident, a diagnosis of NCL should be suspected
      and a skin biopsy should be performed. 

PMID- 24088766
TI  - Disseminated infection and pulmonary embolization of Cunninghamella bertholletiae
      complicated with hemophagocytic lymphohistiocytosis.
AB  - A 22-year-old Japanese woman was diagnosed with hemophagocytic
      lymphohistiocytosis and subsequently was treated with etoposide and
      cyclophosphamide. On Day 22, multiple nodular lesions appeared in the bilateral
      lungs. Neither the administered antibiotics nor the antifungal agent were
      effective, and she died suddenly of respiratory failure on Day 35. An autopsy
      revealed disseminated zygomycosis and a pulmonary infarction due to the
      embolization of an angioinvasive fungus, which was later identified as
      Cunninghamella bertholletiae using in situ hybridization of 18S rRNA. C.
      bertholletiae is aggressive as well as resistant to antifungal agents. This rare
      species should therefore be taken into consideration as a potential causative
      agent of zygomycosis. 

PMID- 24088767
TI  - Recurrent epigastric pain.

PMID- 24088768
TI  - A large mass occupying the entire left atrium.

PMID- 24088769
TI  - Sequential cardiac magnetic resonance imaging of acute eosinophilic myocarditis.

PMID- 24088770
TI  - Brugada-type ST-elevation associated with writhing of a reconstructed esophagus.

PMID- 24088771
TI  - Inverse U shape of the trachea during an asthma attack.

PMID- 24088772
TI  - Spontaneous pneumomediastinum originating from extensive subcutaneous emphysema.

PMID- 24088773
TI  - Urinary tract infection due to "lower" urethral stricture.

PMID- 24088774
TI  - The effect of radial head implant length on radiocapitellar articular properties
      and load transfer within the forearm.
AB  - BACKGROUND: The effect of radial head implant length on forearm biomechanics is
      not well understood. This study examined the influence of an increase or a
      decrease in radial head implant length on forearm load transfer as measured by
      interosseous membrane (IOM) tension and changes in radiocapitellar joint contact
      properties. METHODS: An upper extremity simulator was used to examine 6 cadaveric
      specimens with 5 different radial head implant lengths (-4 mm, -2 mm,
      anatomically correct, +2 mm, and +4 mm). A load-sensing device was woven into the
      fibers of IOM to quantify its tension. An interpositional pressure measurement
      sensor was used to determine radiocapitellar joint contact area and pressure.
      Axial loads of 160 N were applied to the forearm through active pronation and
      supination with the elbow fixed at 90 degrees of flexion. RESULTS: Increasing
      radial head implant length by 4 mm unloaded the IOM in all cases. Decreasing
      implant length by 4 mm significantly increased the IOM tension (P = 0.005). No
      significant differences were found in IOM tension between the correct head
      implant length and the -2 mm implant (P = 0.29). Contact pressure significantly
      increased with increasing radial head implant length (P = 0.021) and contact area
      diminished with both an increase and a decrease in radial head implant length,
      but this was not statistically significant (P = 0.051). CONCLUSIONS: Increasing
      radial head implant length decreased IOM tension and increased radiocapitellar
      joint contact pressure. CLINICAL RELEVANCE: These findings illustrate the
      importance of precise restoration of radial length when performing a radial head
      replacement. If the native radial head length is difficult to accurately assess,
      avoid increasing the length of the radial head to prevent detrimental changes in
      the biomechanics of the forearm and the potential for clinically important
      radiocapitellar joint pathology.

PMID- 24088775
TI  - Mechanism of "Gotfried reduction" in femoral neck fracture.

PMID- 24088776
TI  - Young adults with spina bifida may have higher occurrence of prehypertension and
      hypertension.
AB  - OBJECTIVE: The aims of this study were to determine the occurrence of
      prehypertension and high blood pressure in adults with spina bifida (SB) and to
      examine relationships among blood pressure, cardiovascular disease risk factors,
      and SB-specific factors. DESIGN: This is a cross-sectional, retrospective
      analysis of adults with SB. SB-specific factors and cardiovascular disease risk
      factors were compared among subjects with high blood pressure, subjects with
      blood pressure in the prehypertensive range, and normotensive subjects using the
      chi, Kruskal-Wallis, or Fisher's exact tests. RESULTS: Of 225 subjects, the
      occurrence of prehypertension and high blood pressure was 27% (n = 22) and 27% (n
      = 22) for ages 18-29 yrs, 35% (n = 26) and 41% (n = 30) for ages 30-39 yrs, 18%
      (n = 8) and 66% (n = 29) for ages 40-49 yrs, and 21% (n = 5) and 67% (n = 16) for
      50 yrs or older, respectively. Of the subjects with high blood pressure, 56% were
      men, 14% had obstructive sleep apnea, 14% had diabetes, 19% had renal
      dysfunction, 38% used tobacco, 16% had hydronephrosis, and 71% had a shunt. The
      groups differed significantly with respect to diabetes (P = 0.004), bladder
      procedures (P = 0.001), and renal dysfunction (P < 0.001), with higher
      proportions of subjects with high blood pressure having these comorbidities.
      CONCLUSIONS: Fewer than half of the subjects were considered normotensive. A
      greater proportion of young adults with SB appear to have high blood pressure
      compared with the general United States population. Because elevated blood
      pressure is an independent, modifiable risk factor of cardiovascular disease,
      these findings support early screening and intervention for elevated blood
      pressure in individuals with SB.

PMID- 24088777
TI  - The dose and volume-response relationship of an ethanol-induced tibial nerve
      block in a rabbit model.
AB  - OBJECTIVE: The aim of this study was to observe the dose-response relationship in
      an ethanol-induced tibial nerve block in a rabbit model. DESIGN: Sixteen New
      Zealand white rabbits were separated into three groups that received increasing
      injections of 100% ethanol (0.1, 0.3, and 0.5 ml). All tibial nerves were
      successfully located with a nerve stimulator. Compound muscle action potentials
      were measured before injection; 1, 2, 4, and 7 days after injection; and 2, 3, 4,
      5, 6, 7, and 8 wks after injection. Histologic studies were performed to evaluate
      the destruction of the nerves and surrounding muscles. RESULTS: The compound
      muscle action potential amplitude significantly decreased (P < 0.01) on the first
      day after ethanol injection in all groups. The compound muscle action potential
      amplitude in the 0.1-ml group recovered to baseline by week 2, whereas the 0.3-ml
      group recovered by week 8. The 0.5-ml group did not recover by week 4 (P < 0.01),
      but observations had to stop because of severe complications. The authors found
      that the degrees of axonal degeneration and muscle desmoplasia were related to
      injection volume. CONCLUSIONS: There was a positive linear relationship between
      ethanol injection volume and effect on compound muscle action potential. The safe
      and effective volume of 100% ethanol for a tibial nerve block is 0.3 ml in a
      rabbit model.

PMID- 24088778
TI  - Impact of pressure ulcers on outcomes in inpatient rehabilitation facilities.
AB  - OBJECTIVE: The aim of this study was to examine the impact of pressure ulcers on
      inpatient rehabilitation facility (IRF) outcomes. DESIGN: This is a retrospective
      analysis of the IRF data in the United States from the Uniform Data System for
      Medical Rehabilitation between 2009 and 2011. The study sample included 2902
      pairs of pressure ulcer and pressure ulcer-free patients upon IRF admission,
      matching on age at admission, sex, impairment groups, and comorbidity tier
      measures. The study outcomes were cognition and motor functional gains measured
      by the Functional Independence Measure instrument, IRF length of stay, and
      discharge to the community. RESULTS: The mean pressure ulcer prevalence upon IRF
      admission was 5.23%. After controlling for other covariates under study, the
      pressure ulcer group had a lower motor gain (20.12 vs. 21.58, P < 0.0001), had a
      longer length of stay (16.5 vs. 15.5, P < 0.0001), and were less likely to be
      discharged to the community after IRF stay (odds ratio, 0.72; 95% confidence
      interval, 0.62-0.84) than the patients without a pressure ulcer. CONCLUSIONS: The
      presence of a pressure ulcer among the patients seen in United States IRFs had no
      impact on cognition functional gain but was associated with a minor lower motor
      gain, a longer IRF length of stay, and lower odds of being discharged to the
      community.

PMID- 24088779
TI  - Development and validation of a discharge planning index for achieving home
      discharge after hospitalization for acute stroke among those who received
      rehabilitation services.
AB  - OBJECTIVE: The aim of this study was to develop an index for establishing the
      probability of being discharged home after hospitalization for acute stroke using
      information about previous living circumstances, comorbidities, hospital course,
      and the physical grades and cognitive stages of independence achieved. DESIGN:
      This is a longitudinal observational population-based study. All 6515 persons
      treated for acute stroke who received rehabilitation services in 110 Veterans
      Affairs facilities within a 2-yr period were included. RESULTS: There were eight
      independent predictors of home discharge identified, and points were assigned
      through logistic regression: married (2 points); location before hospitalization
      (extended care = 0 points, other hospital = 9 points, home = 11 points);
      discharge physical grade (grade I, II, or III = 0 points; grade IV or V = 3
      points; grade VI or VII = 5 points); discharge cognitive stage (stage I = 0
      points; stage II, III, IV, or V = 3 points; stage VI or VII = 5 points); and
      absence of liver disease (2 points), mechanical ventilation (3 points), nonoral
      feeding (2 points), and intensive care unit admission (1 point). The points were
      added for all present factors to calculate scores. The probabilities of home
      discharge ranged from 65.03% in the least likely (<=21 points) to 98.24% in the
      most likely group (>=27 points). CONCLUSIONS: The treatment team might apply
      prognostic estimates from this index in discharge planning and functional goal
      setting after initial physical medicine and rehabilitation assessment.

PMID- 24088781
TI  - Efficacy of a checklist as part of a physical medicine and rehabilitation
      clerkship to teach medical students musculoskeletal physical examination skills:
      a prospective study.
AB  - OBJECTIVE: The aim of this study was to evaluate the efficacy of a checklist as
      part of a physical medicine clerkship to teach medical students physical
      examination maneuvers. DESIGN: This is a prospective study performed on fourth
      year medical students enrolled in a 2-wk mandatory clerkship of the Department of
      Physical Medicine and Rehabilitation. At the start and end of the rotation, the
      participating students were tested by performing 20 physical examination
      maneuvers on an investigator who was both the standardized patient and the
      evaluator. At the end of the rotation, the students also completed a survey. Data
      were analyzed using the Bernoulli trial model, with the percentage of students
      who performed the maneuver correctly on the pretest as the a priori probability.
      A full Bonferroni correction was applied. RESULTS: The authors enrolled 141 of
      the 176 fourth year medical students; 121 completed testing. At prerotation,
      approximately 35% of the physical examination maneuvers were performed correctly;
      at postrotation, 82%. For 19 of 20 maneuvers, the improvement was statistically
      significant at P < 0.01. The survey results indicated that the students felt that
      they had limited exposure to musculoskeletal examination skills at prerotation,
      that this rotation helped them achieve competency in performing the maneuvers,
      and that this would improve their future patient care irrespective of field of
      choice. CONCLUSIONS: Considering the high prevalence of musculoskeletal disorders
      and the anticipated rise in the future, the authors strongly recommend teaching
      musculoskeletal physical examination maneuvers in medical school, which can be
      accomplished via a mandatory physical medicine and rehabilitation rotation. The
      authors conclude that checklists as part of this rotation can effectively help in
      teaching physical examination skills to medical students.

PMID- 24088780
TI  - The Uniform Data System for Medical Rehabilitation: report of follow-up
      information on patients discharged from inpatient rehabilitation programs in 2002
      2010.
AB  - OBJECTIVE: The aim of this study was to present yearly aggregated summaries of
      rehabilitation outcomes at admission, discharge, and follow-up from a national
      sample of patients receiving inpatient medical rehabilitation for stroke,
      traumatic brain injury, lower extremity fracture, lower extremity joint
      replacement, traumatic spinal cord injury, or debility. DESIGN: This is an
      analysis of secondary data from more than 300 inpatient rehabilitation facilities
      in the United States that contributed inpatient and follow-up data to the Uniform
      Data System for Medical Rehabilitation during the period January 2002 through
      December 2010. Aggregate variables reported include demographic information,
      social situation, and functional status (Functional Independence Measure
      instrument ratings at admission, discharge, and follow-up). Follow-up data were
      obtained 80-180 days after discharge through telephone interviews by trained
      clinical staff. RESULTS: The final sample included 287,104 patients with follow
      up information. The median time to follow-up was 95 days. Overall, more than 90%
      of the patients within each impairment group were living in the community at
      follow-up. Follow-up Functional Independence Measure total ratings were stable to
      slightly increased over time. Change scores (discharge to follow-up) increased in
      all six groups. The mean Functional Independence Measure gains from discharge to
      follow-up, as a percentage of mean gains from admission to discharge, varied by
      impairment category: 46% for spinal cord injury to 71% for lower extremity
      fracture. Locomotion yielded the lowest ratings at all three assessments within
      each of the six impairment groups. CONCLUSIONS: The follow-up data from the
      national sample of patients discharged from inpatient rehabilitation indicate
      that gains in mean functional independence scores from both admission to
      discharge and discharge to follow-up gradually increased from 2002 to 2010. At
      follow-up, more than nine of ten patients in all six groups are living in the
      community.

PMID- 24088782
TI  - Effect of a hybrid ankle foot orthosis made of polypropylene and fabric in
      chronic hemiparetic stroke patients.
AB  - OBJECTIVE: The ankle foot orthosis (AFO) has been used for control of ankle
      motion in stroke patients for a long time. However, studies on the materials used
      in construction of AFOs have been limited. In this study, the authors attempted
      to investigate the effect of a hybrid AFO made with polypropylene and fabric in
      comparison with a conventional plastic AFO in terms of convenience and effect in
      patients with chronic hemiparetic stroke. DESIGN: Seventeen patients with chronic
      hemiparetic stroke who have used plastic AFOs were recruited for this study. Two
      types of AFOs were used: plastic AFO made with polypropylene and hybrid AFO made
      with polypropylene covered with canvas fabric, which were individually molded and
      fitted. Convenience was evaluated using a self-developed questionnaire on
      patients' satisfaction and weights of AFO, and effect was evaluated using gait
      analysis. RESULTS: On the satisfaction questionnaire, satisfaction was greater
      for the hybrid AFO, and it was lighter in weight than the plastic AFO (P < 0.05).
      In gait analysis, faster walking speed, larger mean and peak ankle dorsiflexion
      angles, and ankle dorsiflexion angles at heel strike and toe off were observed
      for the hybrid and plastic AFOs compared with barefoot (P < 0.05). No significant
      difference was observed between the two orthoses, except for ankle dorsiflexion
      angle at heel strike, in which the plastic AFO showed higher ankle dorsiflexion
      angle than did the hybrid AFO. CONCLUSIONS: According to the results of this
      study, the hybrid AFO showed a similar effect in function, except for ankle
      dorsiflexion angle at heel strike, and was superior with regard to convenience
      compared with the conventional plastic AFO in chronic hemiparetic stroke
      patients. Therefore, it seems that, in general, the hybrid AFO can be recommended
      for hemiparetic stroke patients who require an AFO.

PMID- 24088783
TI  - Sensitive detection of ozone by a practical resorufin-based spectroscopic probe
      with extremely low background signal.
AB  - Ozone (O3) has attracted much attention because of its key role in human health
      and disease, and its detection is of great importance for various biochemical
      studies as well as environmental evaluation. Here we develop a simple and
      practical spectroscopic off-on O3 probe based on resorufin and the specific
      reaction of but-3-enyl with O3. The probe shows an extremely low background
      spectroscopic signal, but reacts with O3 producing a distinct color and
      fluorescence change. The detection limit of the probe for O3 is 5.9 nM, which
      corresponds to an ozone concentration of 0.056 mg m(-3) in air in this study and
      is lower than the international ambient air quality standard of 0.1 mg m(-3).
      More importantly, the proposed probe is worth popularizing, and its applicability
      has been successfully demonstrated on both the determination of O3 in real
      ambient air samples and the imaging of O3 in biological cells. 

PMID- 24088784
TI  - New mercury treaty exposes health risks.
AB  - More than a decade in the making, a new, legally binding treaty on mercury will
      be adopted by governments in the fall of 2013. The treaty's objective is to
      protect human health and the environment from anthropogenic mercury emissions
      through a range of provisions - including an article devoted to reducing exposure
      to mercury. Global emissions have increased since 2005, with the environmental
      health burden increasingly shifting to developing countries. Time is of the
      essence to reduce pollution because (i) exposure risk to mercury is much greater
      than previously thought and (ii) mercury already in the environment can be re
      emitted via processes in the natural cycle, resulting in a longer lag time before
      pollution reduction can have a demonstrable effect on the food chain. Health
      professionals can assist in reducing exposure, choosing mercury-free products and
      urging governments to ratify the treaty as quickly as possible so that it can
      take effect. 

PMID- 24088785
TI  - Requirements for fault-tolerant factoring on an atom-optics quantum computer.
AB  - Quantum information processing and its associated technologies have reached a
      pivotal stage in their development, with many experiments having established the
      basic building blocks. Moving forward, the challenge is to scale up to larger
      machines capable of performing computational tasks not possible today. This
      raises questions that need to be urgently addressed, such as what resources these
      machines will consume and how large will they be. Here we estimate the resources
      required to execute Shor's factoring algorithm on an atom-optics quantum computer
      architecture. We determine the runtime and size of the computer as a function of
      the problem size and physical error rate. Our results suggest that once the
      physical error rate is low enough to allow quantum error correction, optimization
      to reduce resources and increase performance will come mostly from integrating
      algorithms and circuits within the error correction environment, rather than from
      improving the physical hardware. 

PMID- 24088786
TI  - Systematic screen identifies miRNAs that target RAD51 and RAD51D to enhance
      chemosensitivity.
AB  - Homologous recombination mediates error-free repair of DNA double-strand breaks
      (DSB). RAD51 is an essential protein for catalyzing homologous recombination and
      its recruitment to DSBs is mediated by many factors including RAD51, its
      paralogs, and breast/ovarian cancer susceptibility gene products BRCA1/2.
      Deregulation of these factors leads to impaired DNA repair, genomic instability,
      and cellular sensitivity to chemotherapeutics such as cisplatin and PARP
      inhibitors. microRNAs (miRNA) are short, noncoding RNAs that
      posttranscriptionally regulate gene expression; however, the contribution of
      miRNAs in the regulation of homologous recombination is not well understood. To
      address this, a library of human miRNA mimics was systematically screened to
      pinpoint several miRNAs that significantly reduce RAD51 foci formation in
      response to ionizing radiation in human osteosarcoma cells. Subsequent study
      focused on two of the strongest candidates, miR-103 and miR-107, as they are
      frequently deregulated in cancer. Consistent with the inhibition of RAD51 foci
      formation, miR-103 and miR-107 reduced homology-directed repair and sensitized
      cells to various DNA-damaging agents, including cisplatin and a PARP inhibitor.
      Mechanistic analyses revealed that both miR-103 and miR-107 directly target and
      regulate RAD51 and RAD51D, which is critical for miR-103/107-mediated
      chemosensitization. Furthermore, endogenous regulation of RAD51D by miR-103/107
      was observed in several tumor subtypes. Taken together, these data show that miR
      103 and miR-107 overexpression promotes genomic instability and may be used
      therapeutically to chemosensitize tumors. IMPLICATIONS: These findings
      demonstrate a role for miR-103 and -107 in regulating DNA damage repair, thereby
      identifying new players in the progression of cancer and response to
      chemotherapy.

PMID- 24088788
TI  - Polydopamine gradients by oxygen diffusion controlled autoxidation.
AB  - We report a simple and facile protocol to fabricate mussel-inspired polydopamine
      (PDA) gradients on different surfaces. An oxygen diffusion phenomenon was used
      for dopamine autoxidation to form thickness gradients of PDA on different
      substrates. These PDA gradients showed gradual changes in thickness, roughness,
      wettability and light transmittance. 

PMID- 24088789
TI  - Solvent extraction: the coordination chemistry behind extractive metallurgy.
AB  - The modes of action of the commercial solvent extractants used in extractive
      hydrometallurgy are classified according to whether the recovery process involves
      the transport of metal cations, M(n+), metalate anions, MXx(n-), or metal salts,
      MXx into a water-immiscible solvent. Well-established principles of coordination
      chemistry provide an explanation for the remarkable strengths and selectivities
      shown by most of these extractants. Reagents which achieve high selectivity when
      transporting metal cations or metal salts into a water-immiscible solvent usually
      operate in the inner coordination sphere of the metal and provide donor atom
      types or dispositions which favour the formation of particularly stable neutral
      complexes that have high solubility in the hydrocarbons commonly used in recovery
      processes. In the extraction of metalates, the structures of the neutral
      assemblies formed in the water-immiscible phase are usually not well defined and
      the cationic reagents can be assumed to operate in the outer coordination
      spheres. The formation of secondary bonds in the outer sphere using, for example,
      electrostatic or H-bonding interactions are favoured by the low polarity of the
      water-immiscible solvents. 

PMID- 24088787
TI  - Activation of the Wnt pathway through AR79, a GSK3beta inhibitor, promotes
      prostate cancer growth in soft tissue and bone.
AB  - Due to its bone anabolic activity, methods to increase Wnt activity, such as
      inhibitors of dickkopf-1 and sclerostin, are being clinically explored. Glycogen
      synthase kinase (GSK3beta) inhibits Wnt signaling by inducing beta-catenin
      degradation, and a GSK3beta inhibitor, AR79, is being evaluated as an
      osteoanabolic agent. However, Wnt activation has the potential to promote tumor
      growth; therefore, the goal of this study was to determine if AR79 has an impact
      on the progression of prostate cancer. Prostate cancer tumors were established in
      subcutaneous and bone sites of mice followed by AR79 administration, and tumor
      growth, beta-catenin activation, proliferation, and apoptosis were assessed.
      Additionally, prostate cancer and osteoblast cell lines were treated with AR79,
      and beta-catenin status, proliferation (with beta-catenin knockdown in some
      cases), and proportion of ALDH(+)CD133(+) stem-like cells were determined. AR79
      promoted prostate cancer tumor growth, decreased phospho-beta-catenin, increased
      total and nuclear beta-catenin, and increased tumor-induced bone remodeling.
      Additionally, AR79 treatment decreased caspase-3 and increased Ki67 expression in
      tumors and increased bone formation in normal mouse tibiae. Similarly, AR79
      inhibited beta-catenin phosphorylation, increased nuclear beta-catenin
      accumulation in prostate cancer and osteoblast cell lines, and increased
      proliferation of prostate cancer cells in vitro through beta-catenin.
      Furthermore, AR79 increased the ALDH(+)CD133(+) cancer stem cell-like proportion
      of the prostate cancer cell lines. In conclusion, AR79, while being bone
      anabolic, promotes prostate cancer cell growth through Wnt pathway activation.
      IMPLICATIONS: These data suggest that clinical application of pharmaceuticals
      that promote Wnt pathway activation should be used with caution as they may
      enhance tumor growth.

PMID- 24088790
TI  - A prospective validation of the IOTA logistic regression models (LR1 and LR2) in
      comparison to subjective pattern recognition for the diagnosis of ovarian cancer.
AB  - OBJECTIVES: This study aimed to assess the accuracy of the International Ovarian
      Tumour Analysis (IOTA) logistic regression models (LR1 and LR2) and that of
      subjective pattern recognition (PR) for the diagnosis of ovarian cancer. METHODS
      AND MATERIALS: This was a prospective single-center study in a general gynecology
      unit of a tertiary hospital during 33 months. There were 292 consecutive women
      who underwent surgery after an ultrasound diagnosis of an adnexal tumor. All
      examinations were by a single level 2 ultrasound operator, according to the IOTA
      guidelines. The malignancy likelihood was calculated using the IOTA LR1 and LR2.
      The women were then examined separately by an expert operator using subjective
      PR. These were compared to operative findings and histology. The sensitivity,
      specificity, area under the curve (AUC), and accuracy of the 3 methods were
      calculated and compared. RESULTS: The AUCs for LR1 and LR2 were 0.94 [95%
      confidence interval (CI), 0.92-0.97] and 0.93 (95% CI, 0.90-0.96), respectively.
      Subjective PR gave a positive likelihood ratio (LR+ve) of 13.9 (95% CI, 7.84
      24.6) and a LR-ve of 0.049 (95% CI, 0.022-0.107). The corresponding LR+ve and LR
      ve for LR1 were 3.33 (95% CI, 2.85-3.55) and 0.03 (95% CI, 0.01-0.10), and for
      LR2 were 3.58 (95% CI, 2.77-4.63) and 0.052 (95% CI, 0.022-0.123). The accuracy
      of PR was 0.942 (95% CI, 0.908-0.966), which was significantly higher when
      compared with 0.829 (95% CI, 0.781-0.870) for LR1 and 0.836 (95% CI, 0.788-0.872)
      for LR2 (P < 0.001). CONCLUSIONS: The AUC of the IOTA LR1 and LR2 were similar in
      nonexpert's hands when compared to the original and validation IOTA studies. The
      PR method was the more accurate test to diagnose ovarian cancer than either of
      the IOTA models.

PMID- 24088791
TI  - Antioxidant potential of Ulva rigida extracts: protection of HeLa cells against
      H2O2 cytotoxicity.
AB  - The rising demand for natural antioxidants instead of synthetic materials,
      especially in biomedical applications, has led to increased interest in the
      search for bioactive compounds with potent antioxidant activity. In the present
      study, we tested the antioxidant effect of both a crude extract and an ethanol
      precipitate of Ulva rigida in HeLa cells exposed to hydrogen peroxide (H2O2).
      HeLa cells treated with H2O2 (1 mmol l-1 for 3 h) exhibited significant damage to
      their morphology, a significant decrease in cell survival, and a remarkable
      leakage of lactate dehydrogenase (LDH). However, the co-exposure of cells to H2O2
      and the crude extract or ethanol precipitate of U. rigida induced fewer
      morphological cytotoxic effects, a significant increase in cell viability, and a
      significant decrease in LDH release. Biochemical studies have demonstrated that
      U. rigida extracts have a strong radicalscavenging activity and contain protein,
      sugar, and phenolic content. The overall results suggest that U. rigida extracts
      protect HeLa cells from death induced by oxidative stress, and it is likely that
      these effects are related to the phenolic, protein, and polysaccharide compounds
      contained in this alga. Hence, U. rigida can be used to treat diseases ascribed
      to oxidative disorders.

PMID- 24088792
TI  - Comparative ontogenetic changes in enzyme activity during embryonic development
      of calyptraeid gastropods.
AB  - A modification of a semi-quantitative color-based enzyme assay was used to
      quantify the activity of 19 enzymes (5 peptidases, 3 lipases, 3 phosphotases, and
      8 carbohydrases) during five stages of development in eight species of
      calyptraeid gastropods. Sixteen of the 19 enzymes showed a significant effect of
      mode of development on the concentration of the reaction product after incubation
      of homogenates standardized for protein content. The overall pattern was that
      planktotrophs showed the highest activities, followed by adelphophages, and
      nonfeeding embryos, which had the lowest enzyme activities. Thirteen enzymes
      showed significant differences across developmental stages. Of these, eight
      showed a clear increase during development. Only one of the enzymes showed a
      sudden jump in activity between the unfed, pre-hatching stage and post-hatching
      stages that were fed Isochrysis galbana. In three cases, ANOVA identified two
      exclusive, significantly different groups of species. In naphthol-AS-BI
      phosphohydrolase, the measured absorbance of Crucibulum spinosum samples was
      significantly higher than in all of the other species. The activity of alpha
      fucosidase in Crepipatella occulta was significantly greater than in the other
      seven species. Finally, the activity of beta-galactosidase was significantly
      higher in C. occulta, Crucibulum spinosum, and Bostrycapulus calyptraeformis than
      in the four Crepidula species. This is the only enzyme for which there is an
      indication of a phylogenetic effect. Relative enzyme activities were similar to
      those reported for other herbivorous gastropods, with the three
      phosphohydrolases, four carbohydrases (beta-galactosidase, beta-glucuronidase, N
      acetyl-beta-glucosaminidase, and alpha-fucosidase), and leucine arylamidase
      showing high activities. 

PMID- 24088793
TI  - Effects of non-steroidal aromatase inhibitor letrozole on sex inversion and
      spermatogenesis in yellow catfish Pelteobagrus fulvidraco.
AB  - The effects of letrozole (LZ), a potent nonsteroidal aromatase inhibitor (AI), on
      growth performance, sex inversion, and sex changes were investigated in yellow
      catfish (Pelteobagrus fulvidraco), which display sexual dimorphic growth. Growth
      performance was promoted significantly in the low-dose LZ treatment, compared
      with the control. Four LZ treatments produced dose-dependent male proportions
      that were significantly higher than that of the control. Histological examination
      of testes treated by LZ displayed a large amount of spermatozoa and enlarged
      lobule lumens, indicating that LZ treatments can potentially stimulate
      spermatogenesis. Changes of sex proportions 45 days after the end of the LZ
      treatments prove that the female germ cells possess a certain degree of
      bipotentiality. These results suggest that aromatase activity plays a vital role
      in sex differentiation, as in other teleosts, with inhibition of aromatase
      activity by AI bringing about sex inversion. 

PMID- 24088794
TI  - Multiple colonizations lead to cryptic biodiversity in an island ecosystem:
      comparative phylogeography of anchialine shrimp species in the Ryukyu
      Archipelago, Japan.
AB  - Archipelagos of the Indo-West Pacific are considered to be among the richest in
      the world in biodiversity, and phylogeographic studies generally support either
      the center of origin or the center of accumulation hypothesis to explain this
      pattern. To differentiate between these competing hypotheses for organisms from
      the Indo-West Pacific anchialine ecosystem, defined as coastal bodies of
      mixohaline water fluctuating with the tides but having no direct oceanic
      connections, we investigated the genetic variation, population structure, and
      evolutionary history of three caridean shrimp species (Antecaridina lauensis,
      Halocaridinides trigonophthalma, and Metabetaeus minutus) in the Ryukyu
      Archipelago, Japan. We used two mitochondrial genes--cytochrome c oxidase subunit
      I (COI) and large ribosomal subunit (16S-rDNA)--complemented with genetic
      examination of available specimens from the same or closely related species from
      the Indian and Pacific Oceans. In the Ryukyus, each species encompassed 2-3
      divergent (9.52%-19.2% COI p-distance) lineages, each having significant
      population structure and varying geographic distributions. Phylogenetically, the
      A. lauensis and M. minutus lineages in the Ryukyus were more closely related to
      ones from outside the archipelago than to one another. These results, when
      interpreted in the context of Pacific oceanographic currents and geologic history
      of the Ryukyus, imply multiple colonizations of the archipelago by the three
      species, consistent with the center of accumulation hypothesis. While this study
      contributes toward understanding the biodiversity, ecology, and evolution of
      organisms in the Ryukyus and the Indo-West Pacific, it also has potential utility
      in establishing conservation strategies for anchialine fauna of the Pacific Basin
      in general.

PMID- 24088795
TI  - Patterns of activity expressed by juvenile horseshoe crabs.
AB  - Adult American horseshoe crabs, Limulus polyphemus, possess endogenous circadian
      and circatidal clocks controlling visual sensitivity and locomotion,
      respectively. The goal of this study was to determine the types of activity
      rhythms expressed by juvenile horseshoe crabs (n = 24) when exposed to a 14:10
      light/dark cycle (LD) for 10 days, followed by 10 days of constant darkness (DD).
      Horseshoe crab activity was recorded with a digital time-lapse video system that
      used an infrared-sensitive camera so animals could be monitored at night. In LD,
      15 animals expressed daily patterns of activity, 6 displayed a circatidal
      pattern, and the remaining 3 were arrhythmic. Of the 15 animals with daily
      patterns of locomotion, 7 had a significant preference (P < 0.05) for diurnal
      activity and 3 for nocturnal activity; the remainder did not express a
      significant preference for day or night activity. In DD, 13 horseshoe crabs
      expressed circatidal rhythms and 8 maintained a pattern of about 24 h. Although
      these results suggest the presence of a circadian clock influencing circatidal
      patterns of locomotion, these apparent circadian rhythms may actually represent
      the expression of just one of the two bouts of activity driven by the putative
      circalunidian clocks that control their tidal rhythms. Overall, these results
      indicate that, like adults, juvenile horseshoe crabs express both daily and tidal
      patterns of activity and that at least one, and maybe both, of these patterns is
      driven by endogenous clocks. 

PMID- 24088796
TI  - Comparison of the ontogeny of hunting behavior in pharaoh cuttlefish (Sepia
      pharaonis) and oval squid (Sepioteuthis lessoniana).
AB  - Animals adopt various forms of hunting according to their ecological,
      morphological, and cognitive features, and their specific hunting skills are
      acquired ontogenetically in relation to these features. It is noted that
      cuttlefish and squid hunt prey through the elongation of tentacles used
      specifically to capture prey. However, these two cephalopods have different
      lifestyles, leading to questions such as whether hunting skill is acquired
      similarly after birth and whether tentacle elongation is behaviorally identical.
      To address these questions, we observed and compared how captive pharaoh
      cuttlefish (Sepia pharaonis) and oval squid (Sepioteuthis lessoniana) attack prey
      during their early life stages. Like the adults, S. pharaonis hatchlings used the
      tentacular lunge attack, whereas S. lessoniana hatchlings used the arm-opening
      attack. S. lessoniana began to exhibit the tentacular strike attack after 30 days
      of age. In addition to timing of the emergence of a specific hunting mode, some
      differences were observed in the physical aspect of hunting behavior. For
      cuttlefish, maximum tentacle length and maximum speed of tentacle elongation
      increased from hatching to 30 days of age and then decreased. In contrast, for
      squid, maximum tentacle length increased from hatching to 30 days of age and then
      became constant. The distance to prey was positively correlated with maximum
      length and speed of tentacle elongation in S. pharaonis and with maximum swimming
      speed in S. lessoniana. These results show that cuttlefish mainly use an ambush
      strategy and that squid use a pursuit strategy. Possible causes for the
      ontogenetic differences in hunting behavior are discussed. 

PMID- 24088797
TI  - Fluid interactions that enable stealth predation by the upstream-foraging
      hydromedusa Craspedacusta sowerbyi.
AB  - Unlike most medusae that forage with tentacles trailing behind their bells,
      several species forage upstream of their bells using aborally located tentacles.
      It has been hypothesized that these medusae forage as stealth predators by
      placing their tentacles in more quiescent regions of flow around their bells.
      Consequently, they are able to capture highly mobile, sensitive prey. We used
      digital particle image velocimetry (DPIV) to quantitatively characterize the flow
      field around Craspedacusta sowerbyi, a freshwater upstream-foraging hydromedusa,
      to evaluate the mechanics of its stealth predation. We found that fluid
      velocities were minimal in front and along the sides of the bell where the
      tentacles are located. As a result, the deformation rates in the regions where
      the tentacles are located were low, below the threshold rates required to elicit
      an escape response in several species of copepods. Estimates of their encounter
      volume rates were examined on the basis of flow past the tentacles, and trade
      offs associated with tentacle characteristics were evaluated. 

PMID- 24088798
TI  - Sulfonylureas and meglitinides: historical and contemporary issues.
AB  - Insulin secretagogue therapy is commonly used in clinical practice. These agents
      may be utilized as first, second-line or adjunct therapy behind metformin for
      treatment of type 2 diabetes mellitus. Sulfonylureas and meglitinides are
      effective treatments, but cumulative data over decades of research raise concerns
      regarding universal prescribing. The role of insulin secretagogue therapy in beta
      cell failure, blunting of ischemic pre-conditioning, the incidence of
      hypoglycemia - specifically in at-risk populations, modest weight gain and the
      unproven link to cancer are discussed. Ultimately, many of the concerns appear to
      be agent and not class-specific with glibenclamide fairing the worst amongst all
      of the agents discussed. 

PMID- 24088799
TI  - Lipodystrophy: beyond generalization?
AB  - Genetic and acquired lipodystrophies are disorders of adipose tissue
      distribution. In this review we will emphasize its phenotype, metabolic and
      genetic particularities. Special stress will be given to the most prevalent
      lipodystrophy -that associated with HIV infection - describing the similarities
      with congenital lipodystrophies and its pathogenic mechanisms. It will be
      discussed the pathways involved in development, differentiation and death of
      adipocytes, emphasizing that both genetic and acquired, including that associated
      with HIV can induce changes in adipogenesis and how the two main adipose tissue
      dysfunctions - obesity and lipodystrophy - can cause a similar metabolic profile
      (diabetes, hypertension, dyslipidemia) with increased cardiovascular risk. Rare
      monogenic laminopathies and other genetic lipodystrophies could be relevant to
      understand common pathways - physiopathology of aging, atherosclerosis process,
      vascular endothelial cell dysfunction, frailty syndrome and common disorders such
      as type 2 diabetes, insulin resistance, dyslipidemia, hypertension and metabolic
      syndrome. Also, some lipodystrophies can be associated with premature aging and
      precocious cardiovascular disease. The authors aimed to give a focus on the
      particularities of each of the issues addressed. 

PMID- 24088800
TI  - Closer to ideal insulin action: ultra fast acting insulins.
AB  - Mimicking physiologic insulin action has been the main goal of diabetes therapy
      since the discovery of insulin. The evolution of insulin therapy from animal
      insulin to recombinant insulin analogs has improved diabetes treatment
      significantly over the course of years. Nevertheless, the rapid-acting insulin
      analog pharmacokinetics and pharmacodynamics are still far from replicating
      physiologic insulin action resulting in poorly controlled after meal blood
      glucose levels. The slow action of insulin analogs has been a stumbling block for
      the development artificial pancreas systems that require a fast responding
      insulin to blood glucose changes. This review explains the rationale behind the
      undeniable need for ultra-fast acting insulins from a clinical and research
      perspective and summarizes ongoing and future projects to accelerate insulin
      action. 

PMID- 24088801
TI  - Helicobacter pylori infection and diabetes mellitus: the 2013 state of art.
AB  - It is well-known the role of Helicobacter pylori (H. pylori) infection in the
      development of gastroduodenal diseases. From two decades literature has suggested
      the potential relationship of the bacterium with extragastric manifestations. Aim
      of the present review was to analyze the consistency of a potential involvement
      of H. pylori infection in the pathogenesis of diabetes mellitus (DM) as well as
      in the gastric abnormalities associated with this disease. Several studies
      reported a higher prevalence of H. pylori infection in diabetic patients with or
      without dyspeptic symptoms than in controls and a positive association with
      insulin resistance (IR) has been shown. However, DM has a multifactorial
      pathogenesis and the detection of the role of each agent is difficult. The
      different factors implicated in the development of DM as well as of IR include
      inflammation, autoimmunuty, stimulation of innate immune system, trigger to
      platelet activation and platelet-leukocyte aggregation, action on leptin and
      ghrelin regulation, alterated lipid metabolism and insulin sensitivity.
      Effectiveness of H. pylori eradication results significantly lower in diabetic
      patients than in controls, most likely because of the large use of antibiotic in
      DM subjects, causing selection of resistant H. pylori strains. Finally, re
      infection after bacterial eradication, although rarely observed in the general
      population, seems to be more frequent in diabetic patients than in controls. 

PMID- 24088802
TI  - Overexpression of stearoyl-CoA desaturase 1 in bone-marrow mesenchymal stem cells
      increases osteogenesis.
AB  - AIM: The goal of this study was to examine the relationship between stearoyl-CoA
      desaturase 1 (SCD1) and osteogenesis in bone marrow mesenchymal stem cells (BM
      MSCs). METHODS: SCD1 was overexpressed in BM-MSCs using lentiviral transduction.
      Then, osteogenesis was induced by low glucose DMEM (10% fetal bovine serum).
      Alkaline phosphatase (ALP) activity assays, Western blot analyses of SCD1 and
      osteocalcin, and stainings for ALP and alizarin red were done to assess the
      extent of osteogenesis in BM-MSCs. RESULTS: ALP activity was markedly higher in
      the SCD1 overexpressing cells compared with cells transduced with empty vector or
      control (untransduced) cells at 1 and 2 weeks after osteogenic induction. By
      contrast, ALP activities were comparable between control cells and cells
      transduced with empty vector. Western blot analysis demonstrated that osteocalcin
      levels were higher in the SCD1 overexpressing cells, compared with cells
      transduced with empty vector or control cells, at 1 and 2 weeks after osteogenic
      induction. These findings were corroborated by stainings for ALP and alizarin red
      that demonstrated a more active osteogenesis in the SCD1 overexpressing cells 2
      weeks after osteogenic induction. CONCLUSION: Increased levels of SCD1 enhance
      osteogenesis in BM-MSCs.

PMID- 24088803
TI  - Matrine promotes G0/G1 arrest and down-regulates cyclin D1 expression in human
      rhabdomyosarcoma cells.
AB  - Matrine has a broad-spectrum of anti-cancer effects and is efficient in the
      inhibition of proliferation of hepatoma cells, leukemia cells and neuroblastoma
      cell. However, its efficacy and tentative mechanisms in rhabdomyosarcoma have not
      been addressed before. This study aimed to investigate the effects of Matrine on
      cell cycle and expression of cyclin D1 in human rhabdomyosarcoma cells (RD cell
      line). RD cell line was treated with different concentrations (0, 0.5, 1.0, and
      1.5 mg/mL) of Matrine, and cell proliferation and cell cycle were evaluated
      using, respectively, MTT assay and flow cytometry. The effect of Matrine on
      cyclin D1 mRNA levels was measured by RT-PCR. There was a dose-dependent
      inhibition of proliferation in the matrine-treated group (inhibition of
      proliferation rate in control cells 12.70 +/- 0.35%; Matrine-treated cells [0.5,
      1.0, and 1.5 mg/mL]: 31.16 +/- 0.11%, 42.96 +/- 0.9%, and 57.26 +/- 0.8%). The G0
      / G1 ratio in study groups were, respectively, 58.44 +/- 3.57%, 64.79 +/- 2.03%,
      69.97 +/- 2.89% and 75.03 +/- 1.23%.Cyclin D1 mRNA levels progressively
      diminished (control group ratio of cyclin D1 / beta-actin: 0.59 +/- 0.06;
      Matrine: 0.35 +/- 0.05, 0.27 +/- 0.02 and 0.04 +/- 0.03). All aforementioned
      changes were significant (P<0.05). In conclusion, Matrine markedly suppresses
      cell proliferation in RD cells by decreasing expression of cyclin D1 mRNA and
      blocking the cell cycle at the G0 / G1 stage.

PMID- 24088804
TI  - Optimal conditions for "heat-conduct effect" in liver tissue during
      radiofrequency ablation.
AB  - AIM: This study was conducted to optimize the "heat-conduct effect" to increase
      the efficacy of radiofrequency ablation (RFA) in the treatment of liver tumors.
      METHODS: To simulate the "heat-conduct effect" caused by RFA, isolated pig livers
      were heated by an inserted metal tube through which water with different incoming
      temperatures was passed. The tissue temperature was measured within 5- and 10-mm
      radiuses. Further, changes in color and morphology of the tissue were recorded.
      RESULTS: Using an incoming temperature of 70  degrees C, the effective ablation
      radius of 5 mm was achieved within 10 min. To expand the effective radius to 10
      mm, the tube temperature needed to be maintained at above 80  degrees C for 40
      min; alternatively, the tube temperature above 90  degrees C and heating time of
      25 min were also sufficient. CONCLUSION: To achieve the complete ablation in
      isolated liver within the 10 mm radius by "heat-conduct effect", the temperature
      of the heating center should be maintained above 80 - 90  degrees C with the
      exposure time of 25-40 min.

PMID- 24088806
TI  - Efficacy of cefixime-based triple therapy for Helicobacter pylori eradication: a
      retrospective study.

PMID- 24088805
TI  - Efficacy and safety of topiramate in migraine prophylaxis: an open controlled
      randomized study comparing Sincronil and topamax formulations.
AB  - AIM: Topiramate is a small molecule widely used for the treatment of epilepsy,
      migraine, bipolar disorders and alcoholism, and its availability as a generic
      formulation could significantly reduce the National Health Service expenditure. A
      generic formulation, available in Italy under the trademark Sincronil, recently
      showed superimposable blood levels, after oral administration to healthy
      volunteers, with the reference formulation. In the present study we report the
      results of an open label, parallel group, randomized, controlled study performed
      to evaluate the efficacy, tolerability and impact on disability of two different
      formulations of topiramate (Sincronil and Topamax) in patients with migraine
      without aura. METHODS: Sixty patients aged between 18 and 65 years, suffering
      from migraine without aura with an attack frequency of 3-15 attacks/month were
      enrolled and received, after a titration phase lasting 20 days, randomly either
      Sincronil or Topamax at the dose of 25 mg twice daily for 3 months. RESULTS:
      Fifteen out of the 30 patients who were administered Sincronil reported an
      improvement in the clinical condition, with a decrease in the frequency of
      attacks at the 3rd month of treatment higher than 50% with respect to the run-in
      period, 9 reported their clinical condition as being substantially unchanged and
      6 reported that they had suspended the treatment within the first 4 weeks of
      therapy due to side effects. Among the 24 patients who continued treatment up to
      the 3rd month, the frequency of attacks during the 3rd month of treatment was
      significantly decreased from 7 +/- 3.6 to 3.7 +/- 3.7 (P<0.0001), migraine
      severity was reduced from 2.5 +/- 0.5 to 1.7 +/- 0.7 (P<0.0005) and the MIDAS
      score was reduced from 14.3 +/- 4.9 to 8.6 +/- 5.5 (P<0.0001). Sixteen out of the
      30 patients who were administered Topamax reported an improvement in the clinical
      condition with a reduction in the attack frequency at the 3rd month of treatment
      higher than 50% with respect to the run-in period, 10 reported a substantially
      unchanged clinical condition and 4 stopped the treatment within the first weeks
      due to side effects. Among the 26 patients who continued treatment up to the 3rd
      month, headache frequency during the 3rd month of treatment was significantly
      reduced, from 7.3 +/- 2.6 to 3.5 +/- 2.7 (P<0.0001), migraine severity decreased
      from 2.4 +/- 0.6 to 1.6 +/- 0.8 (P<0.0005) and the MIDAS score from 14.1 +/- 4.2
      to 6.8 +/- 4.8 (P<0.0001). CONCLUSION: In conclusion, in this study Topamax
      (reference product) and Sincronil (generic formulation) have proven
      therapeutically equivalent and both products were well tolerated.

PMID- 24088807
TI  - Hyperperfusion in progressive multifocal leukoencephalopathy is associated with
      disease progression and absence of immune reconstitution inflammatory syndrome.
AB  - We sought to characterize perfusion patterns of progressive multifocal
      leukoencephalopathy lesions by arterial spin labelling perfusion magnetic
      resonance imaging and to analyse their association with immune reconstitution
      inflammatory syndrome, and survival. A total of 22 patients with progressive
      multifocal leukoencephalopathy underwent a clinical evaluation and magnetic
      resonance imaging of the brain within 190 days of symptom onset. The presence of
      immune reconstitution inflammatory syndrome was determined based on clinical and
      laboratory criteria. Perfusion within progressive multifocal leukoencephalopathy
      lesions was determined by arterial spin labelling magnetic resonance imaging. We
      observed intense hyperperfusion within and at the edge of progressive multifocal
      leukoencephalopathy lesions in a subset of subjects. This hyperperfusion was
      quantified by measuring the fraction of lesion volume showing perfusion in excess
      of twice normal appearing grey matter. Hyperperfused lesion fraction was
      significantly greater in progressive multifocal leukoencephalopathy progressors
      than in survivors (12.8% versus 3.4% P = 0.02) corresponding to a relative risk
      of progression for individuals with a hyperperfused lesion fraction >= 4.0% of
      9.1 (95% confidence interval of 1.4-59.5). The presence of hyperperfusion was
      inversely related to the occurrence of immune reconstitution inflammatory
      syndrome at the time of scan (P = 0.03). Indeed, within 3 months after symptom
      onset, hyperperfusion had a positive predictive value of 88% for absence of
      immune reconstitution inflammatory syndrome. Arterial spin labelling magnetic
      resonance imaging recognized regions of elevated perfusion within lesions of
      progressive multifocal leukoencephalopathy. These regions might represent
      virologically active areas operating in the absence of an effective adaptive
      immune response and correspond with a worse prognosis. 

PMID- 24088808
TI  - IFN-gamma-dependent activation of the brain's choroid plexus for CNS immune
      surveillance and repair.
AB  - Infiltrating T cells and monocyte-derived macrophages support central nervous
      system repair. Although infiltration of leucocytes to the injured central nervous
      system has recently been shown to be orchestrated by the brain's choroid plexus,
      the immunological mechanism that maintains this barrier and regulates its
      activity as a selective gate is poorly understood. Here, we hypothesized that
      CD4(+) effector memory T cells, recently shown to reside at the choroid plexus
      stroma, regulate leucocyte trafficking through this portal through their
      interactions with the choroid plexus epithelium. We found that the naive choroid
      plexus is populated by T helper 1, T helper 2 and regulatory T cells, but not by
      encephalitogenic T cells. In vitro findings revealed that the expression of
      immune cell trafficking determinants by the choroid plexus epithelium is
      specifically induced by interferon-gamma. Tumour necrosis factor-alpha and
      interferon-gamma reciprocally controlled the expression of their receptors by the
      choroid plexus epithelium, and had a synergistic effect in inducing the
      epithelial expression of trafficking molecules. In vivo, interferon-gamma
      dependent signalling controlled trafficking through the choroid plexus;
      interferon-gamma receptor knockout mice exhibited reduced levels of T cells and
      monocyte entry to the cerebrospinal fluid and impaired recovery following spinal
      cord injury. Moreover, reduced expression of trafficking molecules by the choroid
      plexus was correlated with reduced CD4(+) T cells in the choroid plexus and
      cerebrospinal fluid of interferon-gamma receptor knockout mice. Similar effect on
      the expression of trafficking molecules by the choroid plexus was found in bone
      marrow chimeric mice lacking interferon-gamma receptor in the central nervous
      system, or reciprocally, lacking interferon-gamma in the circulation.
      Collectively, our findings attribute a novel immunological plasticity to the
      choroid plexus epithelium, allowing it to serve, through interferon-gamma
      signalling, as a tightly regulated entry gate into the central nervous system for
      circulating leucocytes immune surveillance under physiological conditions, and
      for repair following acute injury. 

PMID- 24088809
TI  - Neurodegenerative disorders: a PIR-fect storm.

PMID- 24088810
TI  - Detecting awareness after severe brain injury.
AB  - Recent developments in functional neuroimaging have provided a number of new
      tools for assessing patients who clinically appear to be in a vegetative state.
      These techniques have been able to reveal awareness and even allow rudimentary
      communication in some patients who remain entirely behaviourally non-responsive.
      The implications of these results extend well beyond the immediate clinical and
      scientific findings to influencing legal proceedings, raising new ethical
      questions about the withdrawal of nutrition and hydration and providing new
      options for patients and families in that decision-making process. The findings
      have also motivated significant public discourse about the role of neuroscience
      research in society. 

PMID- 24088812
TI  - Correlates and moderators of child pornography consumption in a community sample.
AB  - This study compares pornography users who report child pornography (CP)
      consumption with those who do not on demographic characteristics (age, ethnicity,
      and education level), psychological characteristics (e.g., loneliness, attachment
      style, anxiety, and sensation seeking), frequency of pornography use, and
      intentions to engage in contact sexual abuse. Participants were recruited on the
      Internet to complete an online anonymous survey about "problematic pornography
      use." Approximately, one fifth of the recruited male pornography users (21%, n =
      37) reported consuming CP. The two groups were similar on all demographic and
      psychological characteristics. However, the probability of CP consumption was the
      greatest among men scoring high on a measure of sensation seeking who reported
      frequent pornography use (i.e., statistical moderation). CP consumers also
      reported a greater interest in engaging in sexual contact with a minor than non
      CP consumers. 

PMID- 24088813
TI  - A criminal careers typology of child sexual abusers.
AB  - We present a criminal careers typology of child sexual abusers constructed in
      terms of their offending persistence (persistent vs. limited) and versatility
      (specialized vs. versatile). Analyses were conducted on the official records of
      362 convicted offenders, 213 of whom also provided confidential self-report data
      on their personal and offending histories. Forty-one percent of the sample were
      currently serving sentences for their first sexual offense conviction(s) but had
      at least one prior conviction for a nonsexual offense (limited/versatile); 36.4%
      had no previous convictions of any kind (limited/specialized); 17.8% had prior
      convictions for sexual and nonsexual offenses (persistent/versatile); and 4.8%
      had prior convictions for sexual offenses only (persistent/specialized). These
      four groups differed on a range of personal and offense-related variables,
      including abuse histories, sexual orientation, age at first sexual contact with a
      child, number of victims, duration of sexual involvement with victims, victim
      gender, and whether victims were familial or nonfamilial. These differences
      suggest the need to adopt different treatment and prevention strategies that
      target the specific characteristics of each group. 

PMID- 24088814
TI  - Incorporating change information into sexual offender risk assessments using the
      violence risk scale-sexual offender version.
AB  - We examined the use of risk-change information in sexual offender risk
      assessments featuring the Violence Risk Scale-Sexual Offender version (VRS-SO), a
      sex offender risk assessment and treatment planning tool. The study featured a
      combined international sample of 539 sex offenders followed up an average of 15.5
      years post-release. Pre- and posttreatment VRS-SO ratings were amalgamated from
      two treated samples of sex offenders from Canada and New Zealand. Analyses
      focused on examinations and applications of change data and its relationship to
      sexual and violent recidivism. VRS-SO change scores were significantly associated
      with decreases in these outcome criteria with, and without, controlling for
      indicators of pretreatment risk (e.g., Static-99R score) and individual
      differences in follow-up time. Applications of logistic regression using fixed 5
      year follow-ups generated estimated rates of sexual and violent recidivism at
      different VRS-SO score thresholds. The use of logistic regression demonstrated a
      clinically useful and systematic means of combining risk and change information
      into posttreatment risk appraisals. Implications for the use of change
      information in the assessment and management of sexual offender risk are
      discussed. 

PMID- 24088815
TI  - Probing the importance of ionic liquid structure: a general ionic liquid effect
      on an S(N)Ar process.
AB  - The effect of a range of ionic liquids, with systematic variations in the cation
      and anion, on the rate constant of an aromatic substitution process was
      investigated. Temperature-dependent kinetic data allowed calculation of
      activation parameters for the process in each solvent. These data demonstrate a
      generalised ionic liquid effect, with an increase in rate constant observed in
      each ionic solvent, though the microscopic origins of the rate constant
      enhancement differ with the nature of the ionic liquid. 

PMID- 24088811
TI  - New technologies for examining the role of neuronal ensembles in drug addiction
      and fear.
AB  - Correlational data suggest that learned associations are encoded within neuronal
      ensembles. However, it has been difficult to prove that neuronal ensembles
      mediate learned behaviours because traditional pharmacological and lesion
      methods, and even newer cell type-specific methods, affect both activated and non
      activated neurons. In addition, previous studies on synaptic and molecular
      alterations induced by learning did not distinguish between behaviourally
      activated and non-activated neurons. Here, we describe three new approaches-
      Daun02 inactivation, FACS sorting of activated neurons and Fos-GFP transgenic
      rats--that have been used to selectively target and study activated neuronal
      ensembles in models of conditioned drug effects and relapse. We also describe two
      new tools--Fos-tTA transgenic mice and inactivation of CREB-overexpressing
      neurons--that have been used to study the role of neuronal ensembles in
      conditioned fear.

PMID- 24088817
TI  - Recombinant human lactoferrin induces human and mouse dendritic cell maturation
      via Toll-like receptors 2 and 4.
AB  - Lactoferrin, a key component of innate immunity, is a cationic monomeric 80-kDa
      glycoprotein of the transferrin superfamily. Recombinant human lactoferrin, known
      as talactoferrin (TLF), induces a distinct functional maturation program in human
      dendritic cells (DCs) derived from peripheral blood monocytes. However, the
      receptors and molecular mechanisms involved in this induction have not been fully
      determined. By exploiting genome-wide transcription profiling of immature DCs,
      TNF-alpha- and IL-1beta-matured DCs (m-DCs), and TLF-matured DCs (TLF-DCs), we
      have detected a set of transcripts specific for m-DCs and one specific for TLF
      DCs. Functional network reconstruction highlighted, as expected, the association
      of m-DC maturation with IL-1beta, TNF-alpha, and NF-kappaB, whereas TLF-DC
      maturation was associated with ERK and NF-kappaB. This involvement of ERK and NF
      kappaB transduction factors suggests direct involvement of Toll-like receptors
      (TLRs) in TLF-induced maturation. We have used MyD88 inhibition and siRNA
      silencing TLRs on human DCs and mouse TLR-2-knockout cells, to show that TLF
      triggers the maturation of both human and mouse DCs through TLR-2 and TLR-4.

PMID- 24088816
TI  - Loss of SHP-2 activity in CD4+ T cells promotes melanoma progression and
      metastasis.
AB  - The Src homology 2 domain-containing tyrosine phosphatase 2 (SHP-2) has been
      reported to have both tumor-promoting and tumor-suppressing roles in
      tumorigenesis. However, the role of SHP-2 in tumor immunity remains unclear. Here
      we observed progressively lower levels of phosphorylated SHP-2 in tumor
      associated CD4(+) T cells during melanoma development in a murine model.
      Similarly, the levels of phosphorylated SHP-2 in the CD4(+) T cells of human
      melanoma specimens revealed a decrease paralleling cancer development. The CD4(+)
      T cell-specific deletion of SHP-2 promoted melanoma metastasis in mice.
      Furthermore, SHP-2 deficiency in CD4(+) T cells resulted in the increased release
      of inflammatory cytokines, especially IL-6, and the enhanced accumulation of
      tumor-promoting myeloid-derived suppressor cells (MDSCs) in tumor-bearing mice.
      An IL-6-neutralizing antibody reduced MDSC accumulation and inhibited tumor
      growth in CD4(+) T-cell-specific SHP-2-knockout mice. Our results suggest that
      SHP-2 in CD4(+) T cells plays an important role in preventing melanoma
      progression and metastasis. 

PMID- 24088818
TI  - ErbB2 upregulates the Na+,HCO3(-)-cotransporter NBCn1/SLC4A7 in human breast
      cancer cells via Akt, ERK, Src, and Kruppel-like factor 4.
AB  - Misregulation of acid-base transport plays central roles in cancer development.
      We previously demonstrated the strong up-regulation of the Na(+),HCO3(-)
      cotransporter NBCn1 (SLC4A7) in MCF-7 breast cancer cells by a truncated,
      constitutively active ErbB2 (HER2) receptor, DeltaNErbB2, and showed that NBCn1
      expression and activity are increased in breast cancer tissue from patients.
      Here, we present the first in-depth characterization of an SLC4A7 promoter and
      identify its minimal DeltaNErbB2-sensitive region. Inhibition or siRNA-mediated
      knockdown of PI3K, Akt1, ERK1/2, or Src decreased the NBCn1 protein level in
      DeltaNErbB2-expressing MCF-7 cells by ~50, 60, 30 and 35%, respectively. Further,
      knockdown of the transcription factor Kruppel-like factor 4 (KLF4) reduced NBCn1
      protein expression by ~40%, and KLF4 overexpression increased NBCn1 expression by
      50-80%. In contrast, knockdown of the closely related transcription factor
      specificity protein 1 (Sp1) or transfection with dominant-negative Sp1 increased
      NBCn1 expression by ~35 and ~50%, respectively. NBCn1 expression was also
      increased by stimulation of full-length ErbB1, -2, and -3 receptors in SKBr3
      cells (1.5- and 2-fold by NRG1 or EGF, respectively) or after their exogenous
      expression in MCF-7 cells. Finally, stimulation with NRG1 or EGF more than
      doubled acid extrusion capacity in SKBr3 cells. In conclusion, NBCn1 is strongly
      upregulated by ErbB receptor signaling in a manner involving opposite effects of
      KLF4 and Sp1, transcription factors with central roles in cancer development.
      ErbB-induced up-regulation of NBCn1-mediated acid extrusion may play important
      physiological and pathophysiological roles in the breast epithelium and other
      tissues with high ErbB receptor levels.

PMID- 24088819
TI  - Olympic preparation of a world-class female triathlete.
AB  - Detailed accounts of the training programs followed by today's elite triathletes
      are lacking in the sport-science literature. This study reports on the training
      program of a world-class female triathlete preparing to compete in the London
      2012 Olympic Games. Over 50 wk, she performed 796 sessions (303 swim, 194 bike,
      254 run, 45 strength training), ie, 16 +/- 4 sessions/wk (mean +/- SD). Swim,
      bike, and run training volumes were, respectively, 1230 km (25 +/- 8 km/wk), 427
      h (9 +/- 3 h/wk), and 250 h (5 +/- 2 h/wk). Training tasks were categorized and
      prescribed based on heart-rate values and/or speeds and power outputs associated
      with different blood lactate concentrations. Training performed at intensities
      below her individual lactate threshold (ILT), between the ILT and the onset of
      blood lactate accumulation (OBLA), and above the OBLA for swim were 74% +/- 6%,
      16% +/- 2%, 10% +/- 2%; bike 88% +/- 3%, 10% +/- 1%, 2.1% +/- 0.2%; and run 85%
      +/- 2%, 8.0% +/- 0.3%, 6.7% +/- 0.3%. Training organization was adapted to the
      busy competition calendar (18 events, of which 8 were Olympic-distance
      triathlons) and continuously responded to emerging information. Training volumes
      were 35-80% higher than those previously reported for elite male and female
      triathletes, but training intensity and tapering strategies successfully followed
      recommended best practice for endurance athletes. This triathlete placed 7th in
      London 2012, and her world ranking improved from 14th to 8th at the end of 2012. 

PMID- 24088820
TI  - Getting the broken blastomere out of development.

PMID- 24088821
TI  - Antibacterial properties of a self-cured acrylic resin composed of a polymer
      coated with a silver-containing organic composite antibacterial agent.
AB  - A novel antibacterial polymer, coated with a silver-containing organic composite
      antibacterial agent, was dispersed in a self-cured acrylic resin. Residual viable
      cell count of each oral bacterial and fungal species cultivated on acrylic resin
      specimens containing the antibacterial polymer was significantly decreased when
      compared to those cultivated on specimens prepared from untreated polymer. A
      strong inverse correlation was found between the amount of eluted silver ions and
      the residual viable cell count of all species grown on the antibacterial polymer:
      the lower the viable cell count, the higher the amount of eluted silver ions.
      This clearly indicated the antibacterial activity of silver ions. As the content
      of organic composite antibacterial agent added to the polymer increased from 0.5%
      to 1.5% in 0.5% increments, amount of eluted silver ions significantly increased
      with each 0.5% increment to exert greater antibacterial effect. 

PMID- 24088822
TI  - Influence of light-curing units on the polymerization of low-shrinkage composite
      resins.
AB  - This study examined the effect of various light-curing units (LCUs) on the
      polymerization of low-shrinkage composite resins. Two different types of low
      shrinkage composite resins (silorane-based and methacrylate-based) were light
      cured using a quartz-tungsten-halogen (QTH) (HX) unit, a single-peak light
      emitting diode (LED) (DM) unit, and a dual-peak LED (GL) unit, respectively.
      Among the tested LCUs, HX showed the lowest light attenuation within the
      specimens. Among the specimens, Aelite LS and Venus Diamond showed the highest
      and lowest light attenuation, respectively. Silorane-based Filtek LS showed the
      highest degree of conversion both on the top and bottom surfaces. On the bottom
      surface, Grandio and Aelite LS showed the lowest (4.5-7.1%) and highest (25.0
      40.0%) decrease in the degree of conversion compared to their top surface. For
      different LCUs, within the same resin product, the microhardness was
      significantly different. The silorane-based composite resin showed significantly
      less polymerization shrinkage than the methacrylate-based nanofiller-containing
      composite resins.

PMID- 24088823
TI  - Repair of silorane-based composites: microtensile bond strength of silorane-based
      composites repaired with methacrylate-based composites.
AB  - The purpose of our study was to evaluate the effects of surface treatment on the
      microtensile bond strength (MTBS) of silorane-based composites (Filtek Silorane,
      3M ESPE) repaired with methacrylate-based composites (Ceram X, Dentsply). The
      MTBS were measured before or after thermo-mechanical fatigue simulation (FS). The
      surface conditioning regimes were: no treatment, bonding agent, silane, and
      silane+bonding agent. Before and after FS, no significant differences could be
      observed among the different pretreatment groups. FS did not change the MTBS
      although FS increased the repair strength of Silorane in our previous study under
      the same conditions, and after FS all of the failure modes showed adhesive
      failure, which means that the repair bond strengths between silorane-based
      composite and methacrylate-based composite were not durable. In conclusion,
      within the limitations of this study, with this composite neither bonding agent
      nor silane contributed to an increase in the tensile strength. 

PMID- 24088824
TI  - Influence of surface treatment of glass-ionomers on surface free energy and bond
      strength of resin composite.
AB  - The purpose of this study was to determine the influence of surface treatment of
      glass-ionomer (GIC) on bond strength of resin composite and surface free
      energies. Specimens were prepared and divided into three groups as follows:
      without pretreatment (control), phosphoric acid etching, and air-abrasion.
      Adhesive was applied and resin composite was bonded. For conventional GIC, acid
      etching or air-abrasion increased bond strength (8.5-8.8 MPa) when compared with
      controls (4.7 MPa); however, RMGIC resulted in significantly lower bond strengths
      (10.3-15.8 MPa) than in controls (14.2-20.5 MPa). The value of the gammaS(-)
      component increased when conventional GIC was treated with phosphoric acid or air
      abrasion (60.1-60.5 mJ*m(-2)) when compared with controls (52.8 mJ*m(-2)).These
      results indicate that surface treatment of conventional GIC promoted higher bond
      strength to resin composite and higher Lewis-base components, but decreased bond
      strength for RMGIC. 

PMID- 24088825
TI  - The effects of restorative composite resins on the cytotoxicity of dentine
      bonding agents.
AB  - During restoration of damaged teeth in dental clinics, dentin bonding agents are
      usually overlaid with restorative resin composites. The purpose of this study was
      to investigate the effects of restorative resin composites on cytotoxicity of
      dentin bonding agents. Dentin bonding agents were placed on glass discs, pre
      cured and uncured resin composite discs. Bonding agents on the glass discs and
      composite resins discs were light cured and used for agar overlay cytotoxicity
      testing. Dentin bonding agents on composite resin discs exhibited far less
      cytotoxicity than that on glass discs. The polymerization of resin composite
      increased the surface hardness and decreased the cytotoxicity of bonding agents.
      In conclusion, composite resins in dental restorations are expected to enhance
      the polymerization of dentin bonding agents and reduce the elution of resin
      monomers, resulting in the decrease of cytotoxicity. 

PMID- 24088826
TI  - Development of a new direct core build-up method using a hollow fiber-reinforced
      post.
AB  - We have developed a new direct construction method for core build-up starting
      with the hypothesis that an improvement in pullout strength and a decrease in the
      number of voids in the restorative material will become possible by filling a
      hollow fiber reinforced post with the restorative material from the bottom of the
      root canal. For the pullout test, the hollow post was fixed to the head of a
      mixing tip and inserted into the bottom of a cylinder. The restorative material
      was then injected through the hollow post. The pullout load of the hollow posts
      was significantly higher than that of the solid fiber posts. The number of voids
      observed in the restorative material when using the hollow post was about 1/5 of
      that in the case of the solid post. 

PMID- 24088827
TI  - Micromorphological cellular responses of MC3T3-E1 and RAW264.7 after exposure to
      water-dispersible silver nanoparticles stabilized by metal-carbon sigma-bonds.
AB  - With the continuous progress in nanomaterial development for biomedicine, the
      potential cytotoxicity of nanoparticles is drawing more attention and concern for
      clinical applications. The purpose of this study was to evaluate biological
      responses of new water-dispersible silver nanoparticles (Ag-NPs) stabilized by Ag
      C sigma-bonds in cultured murine macrophages (RAW264.7) and osteoblast-like cells
      (MC3T3-E1) using cell viability and morphological analyses. For RAW264.7, Ag-NPs
      seemed to induce cytotoxicity that was dependent on the Ag-NP concentration.
      However, no cytotoxic effects were observed in the MC3T3-E1 cell line. In
      microscopic analysis, Ag-NPs were taken up by MC3T3-E1 cells with only minor cell
      morphological changes, in contrast to RAW264.7 cells, in which particles
      aggregated in the cytoplasm and vesicles. The ability of endocytosis of
      macrophages may induce harmful effects due to expansion of cell vesicles compared
      to osteoblast-like cells with their lower uptake of Ag-NPs.

PMID- 24088828
TI  - Effect of intermediate ceramics and firing temperature on bond strength between
      tetragonal zirconia polycrystal and veneering ceramics.
AB  - The purpose of the present study was to investigate the influence of the
      intermediate ceramics and firing temperature on bond strength between tetragonal
      zirconia polycrystal (TZP) and its intermediate ceramics. Two types of
      intermediate ceramics, defined as a ceramics placed between the TZP and its
      veneering ceramics, were used; one including high-strength lithium-disilicate
      (EP) or feldspathic liner porcelain (SB). The firing temperature of the
      intermediate ceramics was set at 930 degrees C, 945 degrees C or 960 degrees C.
      Shear bond strength showed values of 35.8 MPa in SB and 54.9 MPa in EP at a
      firing temperature of 960 degrees C. Electron probe microanalysis revealed that
      components of the intermediate ceramics remained on the TZP surface after
      debonding, indicating that fractures occurred in the intermediate ceramics near
      the TZP. These results indicate that the bond strength between and a TZP
      framework and its veneering ceramics could be improved by using a high-strength
      intermediate ceramics and a comparatively high firing temperature. 

PMID- 24088829
TI  - Effects of 2,2,2-trifluoroethyl methacrylate on properties of autopolymerized
      hard direct denture reline resins.
AB  - This study evaluated the effects of the fluorinated monomer of 2,2,2
      trifluoroethyl methacrylate (TFEMA) on the properties of autopolymerized hard
      direct denture reline resins. Iso-butyl methacrylate (i-BMA) and 2-hydroxyethyl
      methacrylate (2-HEMA) containing 30% TFEMA by weight were used as monomers, while
      poly(ethyl methacrylate) was used as a powder. Setting characteristics, dynamic
      mechanical properties, and changes over time, as well as wettability were
      determined by use of an oscillating rheometer, dynamic viscoelastometer, and
      contact angle meter. Water absorption and solubility were also measured according
      to ISO specifications. The reline resin based on i-BMA had greater elasticity and
      stiffness properties, while that based on 2-HEMA showed fewer dynamic mechanical
      property changes over time with the addition of TFEMA. Furthermore, water
      absorption and solubility tended to be reduced and contact angle increased. The
      results of this study suggest that TFEMA improves mechanical properties and
      durability of reline resins over time. 

PMID- 24088830
TI  - Bone formation and osseointegration with titanium implant using granular- and
      block-type porous hydroxyapatite ceramics (IP-CHA).
AB  - The aim of the present study was to examine whether interconnected porous
      hydroxyapatite ceramics (IP-CHA) could be used as bone substitute for implant
      treatment in reconstructive surgery. We firstly assessed if surround of the
      titanium surface placed into granular or block-type IP-CHA can observe new bone
      formation in a rabbit bone defect model. Subsequently, osseointegration and
      stability of titanium implant inserted into block-type IP-CHA was investigated in
      a rabbit onlay graft model. Direct contact between new bone and the surface of
      the titanium in granular- or block-type IP-CHA was found in a rabbit bone defect.
      Further, new bone formation was found in direct contact with the implant surface
      in the block-type IP-CHA in an onlay graft model, and the implant stability
      quotient (ISQ) values were significantly increased after surgery. Therefore, IP
      CHA may be a useful material for implant treatment in reconstructive surgery
      strategies. 

PMID- 24088831
TI  - Efficacy of cold light bleaching using different bleaching times and their
      effects on human enamel.
AB  - This study investigated the efficacy of cold light bleaching using different
      bleaching times and the effects thereof on tooth enamel. Before and after
      bleaching, stained tooth specimens were subjected to visual and instrumental
      colorimetric assessments using Vita Shade Guide and spectrophotometric shade
      matching. Enamel surface alterations were examined using scanning electron
      microscopy (SEM) to analyze surface morphology, surface microhardness (SMH)
      measurement to determine changes in mechanical properties, and X-ray diffraction
      (XRD) to characterize post-bleaching enamel composition. Cold light bleaching
      successfully improved tooth color, with optimal efficacy when bleaching time was
      beyond 10 min. Significant differences in surface morphology were observed among
      the different bleaching times, but no significant differences were observed for
      enamel composition and surface microhardness among the different bleaching times.
      Results of this study revealed an association between the bleaching time of cold
      light bleaching and its whitening efficacy. Together with the results on enamel
      surface changes, this study provided positive evidence to support cold light
      bleaching as an in-office bleaching treatment. 

PMID- 24088832
TI  - Relationship between air-blowing duration and bond strengths of three adhesive
      systems to dentin after thermal aging.
AB  - The purpose was to evaluate the effect of air-blowing duration of three different
      adhesive systems on immediate or thermal aged resin-dentin shear bond strength
      (SBS). Human dentin surfaces were bonded with: one-step (Bond Force, BF), two
      step (FL-Bond II, FLB) and three-step (Scotch Bond Multi-Purpose, SBMP) adhesive
      systems. Bonded surfaces from each group were air-blown for 0, 5, or 10 s and
      cured. Composite cylinders were built on the treated surfaces and cured. Half of
      the specimens from each group were tested immediately and the other halves were
      tested after thermal aging. Statistical analysis showed significant decrease in
      SBS after thermal aging compared to immediate testing in all groups, except BF
      after 5 s air-blowing or FLB and SBMP with no air-blowing (p>0.05). The results
      suggested that 5 s air-blowing is necessary to obtain a stable SBS for BF.
      However, extended airblowing duration of FLB and SBMP decreased the SBS
      significantly after thermal aging. 

PMID- 24088833
TI  - Crystal growth on bioactive glass sputter-coated alumina in artificial saliva.
AB  - In this work, a bioactive glass was deposited on the alumina disk specimens by
      radio-frequency magnetron sputtering to study crystal formation ability in
      artificial saliva. Bioactive glass-coated specimens were immersed in artificial
      saliva for 1 week and 6 months. The specimens were observed with a scanning
      electron microscope (SEM) and the composition was determined by energy dispersive
      spectroscopy (EDS). The crystals that formed on the specimens were analyzed by
      Raman spectroscopic analysis and Micro-X-ray diffraction. SEM photomicrographs
      showed the formation of needle-like structures after immersion for 1 week, and
      tabular structures formed on the surface of the specimen for 6 months. EDS showed
      that both the needle-like and tabular structures were enriched with Ca and P.
      Raman and Micro-XRD spectra for the tabular structure showed peaks that may
      correspond to calcium phosphate. Thus, when immersed in artificial saliva,
      bioactive glass-coated alumina produced a crystal which might be calcium
      phosphate. 

PMID- 24088834
TI  - Fracture resistance of endodontically treated teeth using fiber post with an
      elastic modulus similar to dentin.
AB  - This study investigated the effect of fiber reinforced composite resin (FRC) post
      lengths, ferrule, and full coverage metal crown on fracture resistance of
      endodontically treated teeth (ETT) using an experimental FRC post with the
      similar elastic modulus of dentin (11.5 GPa). ETT was restored according to 1 of
      7 combinations of FRC post length (10, 5, 2.5, 0 mm), ferrule (0, 2 mm), and
      with/without metal crown (n=6). An oblique compressive load was applied on the
      restored teeth using a universal testing machine. Fracture loads were evaluated
      with 1-way ANOVA and Tukey HSD test (p<0.05). Compared with tooth preparation
      only, the fracture loads of ETT restored with composite resin and different post
      lengths were not significantly different. The group with the ferrule with metal
      crown showed significantly greater fracture resistance than the others.

PMID- 24088835
TI  - Wear of metal-free resin composite crowns after three years in service.
AB  - To compare differences between the wear behavior of two types of metal-free resin
      composite crown with a control after three years in clinical service. Sixty-six
      participants needing one to three posterior single crowns were fitted with 120
      crowns. Abutment teeth were randomly assigned to three groups: 40 resin composite
      crowns with fiber-reinforced framework, 40 resin composite crowns without fiber
      reinforced framework, and 40 metal-ceramic crowns. To assess wear, gypsum
      replicas of the crowns were fabricated and scanned with a 3D laser scanner at
      baseline and after three years. Differences between the groups were analyzed by
      use of mixed-effects regression models. Wear of resin composite crowns with fiber
      reinforced framework (p=0.0043) and resin composite crowns without framework
      (p=0.0246) was significantly greater than in the metal-ceramic group. Wear of
      metal-free resin composite crowns after three years was significantly greater
      than that of metal-ceramic crowns, but the wear was still clinically acceptable.

PMID- 24088836
TI  - Effects of coloring agents applied during sintering on bending strength and
      hardness of zirconia ceramics.
AB  - The effects of coloring agents (Vita in-ceram 2000 YZ coloring liquid (VL) and
      IPS e.max ZirCAD (IS)) and shades (1, 3, and 5) applied during sintering on the
      bending strength and fracture toughness of zirconia ceramics was examined. No
      differences in the bending strength or fracture toughness were observed for the
      type of coloring agent used. Moreover, the bending strength and Vickers hardness
      of the zirconia ceramics decreased, while the crack length and fracture toughness
      did not change with the different coloring agents. The marginal borders of the
      indentations formed were clear and linear, and no damage, including chipping, was
      observed. Therefore, clinical application of zirconia ceramics can be recommended
      because the coloring agents and shades applied during sintering have the same
      effect as an opaque layer and cause no significant deterioration of the
      mechanical properties of the zirconia ceramics. 

PMID- 24088837
TI  - Retention behaviors of different attachment systems: precious versus nonprecious,
      precision versus semi-precision.
AB  - The aims of this study were to investigate the retention force changes of
      different attachment systems after 10,000 insertion-separation cycles and the
      difference in retention force between precious and non-precious materials of the
      same attachment system. Four types of attachments (Ball, Rod, M3 stud, and AP
      Piccolino), produced using both precious and non-precious metal alloys, were
      tested (n=6). Data were analyzed using analysis of variance (ANOVA), Tukey's
      multiple comparison test, and t-test at a significance level of p<=0.05.
      Retention forces of all attachment types were significantly decreased after
      10,000 insertion-separation cycles (p<=0.05). Rod and M3 attachment systems
      showed an initial increase in retention force, then an eventual decrease. At the
      end of the test, precious types of M3 and AP-Piccolino attachments had
      significantly higher retention force values than their non-precious ones
      (p<=0.05). Friction between non-precious attachment parts resulted in a higher
      retention loss than precious metal alloys. 

PMID- 24088838
TI  - The impact of zirconium oxide nanoparticles on the hydration chemistry and
      biocompatibility of white Portland cement.
AB  - Zirconium oxide (ZrO2) has been nominated as a radiopacifying agent for use in
      MTA-like Portland cement-based root-filling materials. This research examines the
      impact of 20 wt% ZrO2 nanoparticles in the size range 50 to 75 nm on the early
      hydration chemistry of white Portland cement. Nano-ZrO2 was found to accelerate
      the degree of hydration by 26% within the first 24 h by presenting efficient
      nucleation sites for the precipitation and growth of the early C-S-H gel
      products. The presence of nano-ZrO2 was also found to divert the fate of the
      aluminium-bearing reaction products by lowering the ettringite to monosulphate
      ratio, reducing the size of the ettringite crystals and by increasing the Al:Si
      ratio of the C-S-H gel phase. The chemical and microstructural changes conferred
      upon the cement matrix by the nano-ZrO2 particles had a positive impact on in
      vitro biocompatibility with respect to MG63 osteosarcoma cells (via MTT assay).

PMID- 24088839
TI  - Effect of fiber post length and bone level on the fracture resistance of
      endodontically treated teeth.
AB  - This study evaluated the combined influence of horizontal bone loss and post
      length on the fracture resistance of endodontically treated teeth (ETT). Twenty
      premolars were endodontically treated and divided into four groups of two
      different post insertion depths (5 and 7 mm) and two alveolar bone levels from
      cement-enamel junction (2 and 5 mm). After posts (RelyX Fiber Post) were cemented
      using a self-adhesive resin cement (RelyX Unicem Aplicap) and cores were built up
      (Filtek Supreme XT Universal Restorative, 3M ESPE, USA), cobalt-chrome copings
      were luted to each prepared tooth. All specimens were subjected to thermocycling
      and mechanical loading until fracture occurred. Mean fracture loads (N) were
      1,445+/-342.2 (2 mm bone level/5 mm depth), 1,516+/-413.4 (2 mm bone level/7 mm
      depth), 1,736.4+/-1113.8 (5 mm bone level/5 mm depth), 1,038.6+/-600.2 (5 mm bone
      level/7 mm depth). No significant differences were found. Therefore, bone level
      and post length did not seem to influence the fracture resistance of ETT. 

PMID- 24088840
TI  - Evaluation of the responses of MHC class II molecule-expressing cells and
      macrophages to epoxy resin-based and 4-META-containing, methacrylate resin-based
      root canal sealers in rat subcutaneous tissue.
AB  - Major histocompatibility complex (MHC) class II molecule-expressing cells and
      macrophages play a pivotal role in mediating the host tissue response to
      biomaterials. This study investigated the responses of these cells to epoxy resin
      based and 4-META-containing, methacrylate resin-based endodontic sealers (AH Plus
      and MetaSEAL respectively) in rat connective tissue. Silicone tubes loaded with
      one of the sealers or solid silicone rods (control) were subcutaneously implanted
      in male Wistar rats for three time periods of 7, 14, or 28 days. Tissue specimens
      were immunoperoxidase-stained for MHC class II molecules and CD68 (a general
      macrophage marker). Results showed that AH Plus-implanted tissue displayed
      significantly more MHC class II-positive cells than the control at 14 and 28
      days, whereas MetaSEAL-implanted tissue showed significantly more CD68-positive
      cells than both AH Plus-implanted tissue and the control at all time periods. It
      was concluded that the epoxy resin-based sealer induced the infiltration of MHC
      class II molecule-expressing cells, whereas 4-META-containing, methacrylate resin
      based sealer elicited macrophage infiltration. 

PMID- 24088841
TI  - Effect of calcium chloride solution immersion on surface hardness of restorative
      glass ionomer cements.
AB  - The objective of this study was to evaluate the effect of the concentration of
      calcium chloride (CaCl2) solution on the surface hardness of restorative glass
      ionomer cements (GICs). Two high-viscosity GICs, Fuji IX GP and GlasIonomer FX
      II, were immersed in several concentrations of CaCl2 solution for 1 day and 1
      week. The immersed specimen surfaces were evaluated using microhardness testing,
      grazing incidence X-ray diffraction, and energy-dispersive X-ray spectroscopy.
      Immersion in a higher concentration of CaCl2 solution produced a greater increase
      in the surface hardness. No crystalline substance was observed on the immersed
      surface. Calcium ions were selectively absorbed in the matrix of the GIC surface
      after immersion. They reacted with the non-reacted carboxylic acid groups
      remaining in the cement matrix. These reactions were considered to cause an
      increase in the surface hardness of the GICs. 

PMID- 24088842
TI  - Composite resin vs resin cement for luting of indirect restorations: comparison
      of solubility and shrinkage behavior.
AB  - The aim of this study was to evaluate relationship between shrinkage development
      and early solubility of two commonly used luting materials, a self-adhesive
      cement (GCem chemical and light cured) and composite resin (Tetric). Linear
      displacement, shrinkage forces and leaching of UDMA from specimens immersed in
      75% ethanol/25% water were measured. The least amount of linear shrinkage (33.0+/
      2.9 um) and polymerization force (4.1+/-0.3 kg) was observed in Tetric. UDMA
      leaching (% ug/mL) was the following: chemically cured GCem (4.2+/-0.2)>light
      cured GCem (1.5+/-0.1)>Tetric (0.1). Shrinkage development in the early stages of
      polymerization was much slower in the self-cured specimens in respect to light
      cured ones. With the chemically cured self-adhesive cement, incomplete materials'
      setting during the initial stages after polymerization favored monomer leaching
      from the cements' mass. 

PMID- 24088843
TI  - Compatibility of Ce-TZP/Al2O3 nanocomposite frameworks and veneering porcelains.
AB  - The aim of this study was to examine the compatibility of Ce-TZP/Al2O3
      nanocomposite (CTA) frameworks and veneering porcelains using the Schwickerath
      crack initiation test and clarify the effects on debonding/crack initiation
      strength (DIS) of both surface pretreatment (include heat treatment) of the
      frameworks, type of veneering porcelain varying the coefficient of thermal
      expansion (CTE), and surface roughness of the frameworks. The surfaces of Ce
      TZP/Al2O3 plates were mechanically treated and followed by post-heat treatment.
      The liner and body porcelains were built up and fired according to the
      manufacturer's instructions. Surface analyses of the fractured plates showed
      compatibility with liner porcelains. Since no statistically difference in the DIS
      was found amongst the different surface treatments, post-heat treatments don't be
      mandatory. Whereas, since differences in DIS were found when different porcelains
      with different CTE were used, we concluded the matching of CTE of the porcelain
      with that of Ce-TZP/Al2O3 was important for successful all-ceramic restorations
      using Ce-TZP/Al2O3 frameworks. 

PMID- 24088844
TI  - The usefulness of a haptic virtual reality simulator with repetitive training to
      teach caries removal and periodontal pocket probing skills.
AB  - Our aim was to evaluate haptic virtual reality (VR) simulation with repetitive
      training as a tool in teaching caries removal (CR) and periodontal pocket probing
      (PPP) skills. For the CR simulation, multilayered virtual models composed of
      tooth substance, caries, and pulp were developed. Seven students completed three
      training sessions each, which were scored based on the volume of the cut region,
      the number of instances of handpiece overload, and total cutting time. For the
      PPP task, we developed a virtual periodontal disease model and 26 students
      received training in measuring pocket depth. Pocket probing force was measured
      and proficiency was evaluated. In the CR task, scores for the second and third
      training sessions were significantly higher than for the first training session.
      We likewise obtained effective repetitive training results for the PPP task. Our
      simulator was effective at teaching hand skills for both tasks within short-term
      evaluation. 

PMID- 24088845
TI  - Marginal leakage of class V cavities restored with silorane-based and
      methacrylate-based resin systems.
AB  - The aim of this study was to compare the microleakage of class V cavities
      restored by silorane resin with those restored by the methacrylate resin system.
      Sixty standardized class V cavities were prepared on premolars. The teeth were
      restored with Filtek(TM) Silorane and Silorane(TM) System Adhesive, Filtek(TM)
      Silorane and Adper(TM) Easy One and Filtek(TM) Supreme XT and Adper(TM) Easy One.
      The area and the depth of dye leakage were measured. Considering dye leakage
      area, the best results were achieved in group I (mean-M=0.114+/-0.083 mm(2)),
      then in group III (M=0.384+/-0.480 mm(2)) and finally in group II (M=5.389+/
      6.587 mm(2)). Considering the depth of dye leakage, there was a significant
      difference between group I (mean rank-m.r.=1.23+/-0.44 mm) and II (1.98+/-0.83
      mm), group II and III (1.23+/-0.40 mm). In this study silorane composite and its
      adhesive showed less microleakage than the methacrylate composite, and it showed
      compatibility only with its assigned adhesive. CLINICAL SIGNIFICANCE: Less
      microleakage of silorane restorations could provide better and long lasting
      composite fillings.

PMID- 24088846
TI  - External quality assessment for Avian Influenza A (H7N9) Virus detection using
      armored RNA.
AB  - An external quality assessment (EQA) program for the molecular detection of avian
      influenza A (H7N9) virus was implemented by the National Center for Clinical
      Laboratories (NCCL) of China in June 2013. Virus-like particles (VLPs) that
      contained full-length RNA sequences of the hemagglutinin (HA), neuraminidase
      (NA), matrix protein (MP), and nucleoprotein (NP) genes from the H7N9 virus
      (armored RNAs) were constructed. The EQA panel, comprising 6 samples with
      different concentrations of armored RNAs positive for H7N9 viruses and four H7N9
      negative samples (including one sample positive for only the MP gene of the H7N9
      virus), was distributed to 79 laboratories in China that carry out the molecular
      detection of H7N9 viruses. The overall performances of the data sets were
      classified according to the results for the H7 and N9 genes. Consequently, we
      received 80 data sets (one participating group provided two sets of results)
      which were generated using commercial (n = 60) or in-house (n = 17) reverse
      transcription-quantitative PCR (qRT-PCR) kits and a commercial assay that
      employed isothermal amplification method (n = 3). The results revealed that the
      majority (82.5%) of the data sets correctly identified the H7N9 virus, while
      17.5% of the data sets needed improvements in their diagnostic capabilities.
      These "improvable" data sets were derived mostly from false-negative results for
      the N9 gene at relatively low concentrations. The false-negative rate was 5.6%,
      and the false-positive rate was 0.6%. In addition, we observed varied diagnostic
      capabilities between the different commercially available kits and the in-house
      developed assays, with the assay manufactured by BioPerfectus Technologies
      (Jiangsu, China) performing better than the others. Overall, the majority of
      laboratories have reliable diagnostic capacities for the detection of H7N9 virus.

PMID- 24088847
TI  - Qualitative Analysis To Ascertain Genotypic Identity of or Differences between
      Mycobacterium tuberculosis Isolates in Laboratories with Limited Resources.
AB  - Mycobacterium tuberculosis is currently genotyped using mycobacterial
      interspersed repetitive-unit-variable-number tandem-repeat (MIRU-VNTR) typing,
      although the high cost of this technique restricts its implementation in resource
      limited settings. We designed a MIRU-VNTR format, MLP3 (MIRU-VNTR length
      polymorphism triplex), that is based on the qualitative comparison of 5
      nonfluorescent 3-band fingerprints in conventional electrophoresis and minimizes
      costs and technical demands. MLP3 successfully resolved cross-contamination
      alerts, discriminated reinfections from reactivations, clarified suspected
      microepidemics, and tracked transmission events of high epidemiological interest.

PMID- 24088848
TI  - Emergence of an oseltamivir-resistant influenza A/H3N2 virus in an elderly
      patient receiving a suboptimal dose of antiviral prophylaxis.
AB  - We report the emergence of an influenza virus A/H3N2-E119V neuraminidase variant
      from an elderly patient with renal dysfunction who received a suboptimal dose of
      oseltamivir prophylaxis. In neuraminidase inhibition assays, the E119V variant
      showed a 413-fold increase in the 50% inhibitory oseltamivir concentration and
      grew at titers comparable to those of the wild type in vitro. 

PMID- 24088850
TI  - Impact of the New Abbott mPLUS feature on clinical laboratory efficiencies of
      abbott RealTime assays for detection of HIV-1, Hepatitis C Virus, Hepatitis B
      Virus, Chlamydia trachomatis, and Neisseria gonorrhoeae.
AB  - Diagnostic laboratories are under increasing pressure to improve and expand their
      services. Greater flexibility in sample processing is a critical factor that can
      improve the time to results while reducing reagent waste, making laboratories
      more efficient and cost-effective. The introduction of the Abbott mPLUS feature,
      with the capacity for extended use of amplification reagents, significantly
      increases the flexibility of the m2000 platform and enables laboratories to
      customize their workflows based on sample arrival patterns. The flexibility in
      sample batch size offered by mPLUS enables significant reductions in processing
      times. For hepatitis B virus tests, a reduction in sample turnaround times of up
      to 30% (105 min) was observed for batches of 12 samples compared with those for
      batches of 24 samples; for Chlamydia trachomatis/Neisseria gonorrhoeae tests, the
      ability to run batches of 24 samples reduced the turnaround time by 83% (54 min)
      compared with that for batches of 48 samples. Excellent correlations between
      mPLUS and m2000 standard condition results were observed for all RealTime viral
      load assays evaluated in this study, with correlation r values of 0.998 for all
      assays tested. For the qualitative RealTime C. trachomatis/N. gonorrhoeae assay,
      the overall agreements between the two conditions tested were >98% for C.
      trachomatis and 100% for N. gonorrhoeae. Comparable precision results were
      observed for the two conditions tested for all RealTime assays. The enhanced
      mPLUS capability provides clinical laboratories with increased efficiencies to
      meet increasingly stringent turnaround time requirements without increased costs
      associated with discarding partially used amplification reagents. 

PMID- 24088849
TI  - Large oligoclonal outbreak due to Klebsiella pneumoniae ST14 and ST26 producing
      the FOX-7 AmpC beta-lactamase in a neonatal intensive care unit.
AB  - A large outbreak caused by expanded-spectrum cephalosporin-resistant Klebsiella
      pneumoniae (ESCRKP) was observed in a neonatal intensive care unit (NICU) in
      central Italy. The outbreak involved 127 neonates (99 colonizations and 28
      infections, with seven cases of sepsis and two deaths) over a period of more than
      2 years (February 2008 to April 2010). Characterization of the 92 nonredundant
      isolates that were available for further investigation revealed that all of them
      except one produced the FOX-7 AmpC-type beta-lactamase and belonged to either
      sequence type 14 (ST14) or ST26. All of the FOX-7-positive isolates were
      resistant to cefotaxime, ceftazidime, and piperacillin-tazobactam, while 76% were
      susceptible to cefepime, 98% to ertapenem, 99% to meropenem, and 100% to
      imipenem. The two carbapenem-nonsusceptible isolates had alterations in the genes
      encoding outer membrane proteins K35 and K36, which resulted in truncated and
      likely nonfunctional proteins. The outbreak was eventually controlled by the
      reinforcement of infection control measures based on a multitiered interventional
      approach. This is the first report of a large NICU outbreak caused by ESCRKP
      producing an AmpC-type enzyme. This study demonstrates that AmpC-type enzyme
      producing strains can cause large outbreaks with significant morbidity and
      mortality effects (the mortality rate at 14 days was 28.5% for episodes of
      sepsis), and it underscores the role of laboratory-based surveillance and
      infection control measures to contain similar episodes. 

PMID- 24088851
TI  - Presence of cross-reactions with other viral encephalitides in the indirect
      fluorescent-antibody test for diagnosis of rabies.
AB  - The antemortem diagnosis of rabies in humans employs techniques that require
      accuracy, speed, and sensitivity. A combination of histochemical analysis, in
      vitro virus isolation, immunological methods, and molecular amplification
      procedures are utilized in efforts to diagnose the disease. Modern medicine now
      offers potentially life-saving treatment for a disease that was considered
      invariably fatal once clinical signs develop. However, medical intervention
      efforts require a rapid and accurate diagnosis as early in the course of clinical
      disease as possible. Indirect fluorescent-antibody (IFA) testing on cerebrospinal
      fluid and serum specimens provides rapid results, but the specificity of the
      assay has not been well studied. Because false-positive IFA results could
      significantly affect patient treatment and outcomes, it is critical to understand
      the specificity of this assay. In this study, IFA testing was performed on 135
      cerebrospinal fluid and serum specimens taken from patients with viral
      encephalitis or a presumed viral infection involving an agent other than rabies
      virus. Results indicate that false-positive results can occur in interpreting the
      rabies IFA test. Staining patterns morphologically similar to antirabies staining
      were observed in 7 of the 135 cerebrospinal fluid specimens examined. In
      addition, a majority of the cerebrospinal fluid specimens tested from patients
      with encephalitis presented immunoglobulin that bound to antigens present in the
      cell culture substrate. Of marked concern was the frequent presence of cross
      reactive antibodies in encephalitis cases associated with West Nile and Powassan
      flaviviruses. Because IFA testing for rabies on human specimens may result in
      false-positive results, it should not be used as the sole basis for initiating
      antirabies treatment. 

PMID- 24088852
TI  - Clinical prediction and diagnosis of neurosyphilis in HIV-infected patients with
      early Syphilis.
AB  - The diagnosis of neurosyphilis (NS) is a challenge, especially in HIV-infected
      patients, and the criteria for deciding when to perform a lumbar puncture (LP) in
      HIV-infected patients with syphilis are controversial. We retrospectively
      reviewed demographic, clinical, and laboratory data from 122 cases of HIV
      infected patients with documented early syphilis who underwent an LP to rule out
      NS, and we evaluated 3 laboratory-developed validated real-time PCR assays, the
      Treponema pallidum particle agglutination (TPPA) assay, the fluorescent
      treponemal antibody absorption (FTA-ABS) assay, and the line immunoassay INNO-LIA
      Syphilis, for the diagnosis of NS from cerebrospinal fluid (CSF) samples of these
      patients. NS was defined by a reactive CSF-VDRL test result and/or a CSF white
      blood cell (WBC) count of >20 cells/MUl. Thirty of the 122 patients (24.6%) had
      early NS. Headache, visual symptoms, a CD4 cell count of <500 cells/MUl, and
      viremia, as defined by an HIV-1 RNA count of >=50 copies/ml, were associated with
      NS in multivariate analysis (P = <0.001 for each factor). Blood serum rapid
      plasma reagin (RPR) titers were not associated with early NS (P = 0.575). For the
      diagnosis of NS, the PCR, FTA-ABS, TPPA, and INNO-LIA assays had sensitivities of
      58%, 100%, 68%, and 100%, specificities of 67%, 12%, 49%, and 13%, and negative
      predictive values of 85%, 100%, 84%, and 100%, respectively. Visual disturbances,
      headache, uncontrolled HIV-1 viremia, and a CD4 cell count of <500 cells/MUl were
      predictors of NS in HIV-infected patients with early syphilis, while blood serum
      RPR titers were not; therefore, RPR titers should not be used as the sole
      criterion for deciding whether to perform an LP in early syphilis. When applied
      to CSF samples, the INNO-LIA Syphilis assay easily helped rule out NS. 

PMID- 24088853
TI  - wzi Gene sequencing, a rapid method for determination of capsular type for
      Klebsiella strains.
AB  - Pathogens of the genus Klebsiella have been classified into distinct capsular (K)
      types for nearly a century. K typing of Klebsiella species still has important
      applications in epidemiology and clinical microbiology, but the serological
      method has strong practical limitations. Our objective was to evaluate the
      sequencing of wzi, a gene conserved in all capsular types of Klebsiella
      pneumoniae that codes for an outer membrane protein involved in capsule
      attachment to the cell surface, as a simple and rapid method for the prediction
      of K type. The sequencing of a 447-nucleotide region of wzi distinguished the K
      type reference strains with only nine exceptions. A reference wzi sequence
      database was created by the inclusion of multiple strains representing K types
      associated with high virulence and multidrug resistance. A collection of 119
      prospective clinical isolates of K. pneumoniae were then analyzed in parallel by
      wzi sequencing and classical K typing. Whereas K typing achieved typeability for
      81% and discrimination for 94.4% of the isolates, these figures were 98.1% and
      98.3%, respectively, for wzi sequencing. The prediction of K type once the wzi
      allele was known was 94%. wzi sequencing is a rapid and simple method for the
      determination of the K types of most K. pneumoniae clinical isolates. 

PMID- 24088854
TI  - Superior sensitivity and decreased time to detection with the Bactec Peds Plus/F
      system compared to the BacT/Alert Pediatric FAN blood culture system.
AB  - Here, we compare the sensitivities and times to detection (TTD) of BacT/Alert
      Pediatric FAN (PF) and Bactec Peds Plus blood culture bottles. Test bottles were
      inoculated with 2 ml of banked whole blood, 1-ml aliquots of antibiotic
      suspension, and organisms diluted to simulate a bacteremia level of 10 to 100
      CFU/ml. The control bottles were inoculated with 3 ml of banked blood and
      organism suspensions only. The organism-drug combinations were Staphylococcus
      epidermidis and vancomycin, methicillin-resistant Staphylococcus aureus and
      vancomycin, Streptococcus pneumoniae, vancomycin, and ceftriaxone, Streptococcus
      agalactiae, ampicillin, and cefotaxime, Escherichia coli, cefotaxime, and
      cefepime, Pseudomonas aeruginosa, piperacillin-tazobactam, cefepime, and
      gentamicin, Neisseria meningitidis and ceftriaxone, and Haemophilus influenzae
      and ceftriaxone. The control and test bottle combinations were tested in
      duplicate. The bottles were incubated for 5 days; 32 control and 104 test bottles
      were incubated. Overall, the bacterial recovery rates for the PF and Peds Plus
      bottles were 37% and 62%, 94% and 100% in the controls, 19% and 50% in the test
      bottles, and 33% and 92% in the bottles with vancomycin, respectively. No
      bacteria were recovered from the bottles with S. pneumoniae, S. agalactiae, E.
      coli, N. meningitidis, or H. influenzae in combination with cefotaxime or
      ceftriaxone. The Peds Plus system detected P. aeruginosa in bottles with cefepime
      and piperacillin-tazobactam, but the PF system recovered bacteria only in bottles
      with trough levels of piperacillin-tazobactam. The mean TTD were shorter in the
      Peds Plus system controls (14.2 versus 18.0 h; P = 0.001) and the test bottles
      (14.3 versus 17.8 h; P = 0.008) than in the PF bottles. Overall, we demonstrated
      superior sensitivity, TTD, and antibiotic neutralization in the Bactec Peds Plus
      system compared to those in the Pediatric FAN system. 

PMID- 24088855
TI  - An atypical Clostridium strain related to the Clostridium botulinum group III
      strain isolated from a human blood culture.
AB  - A nontoxigenic strain isolated from a fatal human case of bacterial sepsis was
      identified as a Clostridium strain from Clostridium botulinum group III, based on
      the phenotypic characters and 16S rRNA gene sequence, and was found to be related
      to the mosaic C. botulinum D/C strain according to a multilocus sequence analysis
      of 5 housekeeping genes. 

PMID- 24088856
TI  - Marseillevirus adenitis in an 11-month-old child.
AB  - A Marseillevirus (giant virus of amoeba) has been found in the blood and stool
      samples of individuals who otherwise appear to be healthy. During an attempt to
      define a serological cutoff for Marseillevirus by enzyme-linked immunosorbent
      assay (ELISA) in children, we serendipitously detected high antibody responses to
      Marseillevirus in an 11-month-old boy suffering from adenitis. Marseillevirus DNA
      was then found in his blood using PCR and with a unique sequence. We identified
      Marseillevirus in a lymph node using fluorescence in situ hybridization (FISH)
      and immunohistochemistry, and the lymph node was removed surgically. The child
      was declared to be cured 1 year later. We conclude that adenitis during early
      childhood may be caused by Marseillevirus. 

PMID- 24088857
TI  - Evaluation of commercially available reagents for diagnosis of histoplasmosis
      infection in immunocompromised patients.
AB  - Urinary histoplasma antigen measurement can be useful for diagnosing systemic
      histoplasmosis and for monitoring treatment response, especially in
      immunocompromised patients. However, testing has traditionally been limited to
      specialized reference laboratories, as immunoassay reagents for the antigen were
      not widely available. Recently, a polyclonal-antibody-based in vitro diagnostic
      (IVD) kit for histoplasma antigen detection was released, as well as monoclonal
      antibody reagents against the target. We evaluated the analytical and clinical
      performance of the two reagents. Both assays were capable of detecting
      histoplasma antigen in urine samples over a wide dynamic range, although the
      monoclonal assay showed improved precision and analytical sensitivity relative to
      the polyclonal IVD. In a test set of clinically characterized patient samples,
      the monoclonal laboratory-developed test (LDT) demonstrated 90.5% sensitivity and
      96.3% specificity versus 61.9% sensitivity and 79.3% specificity for the
      polyclonal IVD, with areas under the curve (AUCs) of 0.987 and 0.754,
      respectively. The major differences between the two assays were higher background
      reactivity in healthy donors with the polyclonal assay and an increased signal
      response in positive samples for the monoclonal assay. The impact of these
      differences on monitoring treatment response was evaluated in a series of
      patients undergoing treatment for histoplasmosis. While all the assays gave
      similar qualitative estimates of treatment response, responses were more evident
      using the monoclonal assay. In summary, we conclude that while multiple assays
      are available for measuring histoplasma antigen in urine, a monoclonal-antibody
      based assay appears to provide improved analytical performance for management of
      immunocompromised histoplasmosis patients. 

PMID- 24088858
TI  - Detection of canine pneumovirus in dogs with canine infectious respiratory
      disease.
AB  - Canine pneumovirus (CnPnV) was recently identified during a retrospective survey
      of kenneled dogs in the United States. In this study, archived samples from pet
      and kenneled dogs in the United Kingdom were screened for CnPnV to explore the
      relationship between exposure to CnPnV and the development of canine infectious
      respiratory disease (CIRD). Within the pet dog population, CnPnV-seropositive
      dogs were detected throughout the United Kingdom and Republic of Ireland, with an
      overall estimated seroprevalence of 50% (n = 314/625 dogs). In the kennel
      population, there was a significant increase in seroprevalence, from 26% (n =
      56/215 dogs) on the day of entry to 93.5% (n = 201/215 dogs) after 21 days (P
      <0001). Dogs that were seronegative on entry but seroconverted while in the
      kennel were 4 times more likely to develop severe respiratory disease than those
      that did not seroconvert (P < 0.001), and dogs with preexisting antibodies to
      CnPnV on the day of entry were significantly less likely to develop respiratory
      disease than immunologically naive dogs (P < 0.001). CnPnV was detected in the
      tracheal tissues of 29/205 kenneled dogs. Detection was most frequent in dogs
      with mild to moderate respiratory signs and histopathological changes and in dogs
      housed for 8 to 14 days, which coincided with a significant increase in the risk
      of developing respiratory disease compared to the risk of those housed 1 to 7
      days (P < 0.001). These findings demonstrate that CnPnV is present in the United
      Kingdom dog population; there is a strong association between exposure to CnPnV
      and CIRD in the kennel studied and a potential benefit in vaccinating against
      CnPnV as part of a wider disease prevention strategy. 

PMID- 24088859
TI  - Comparison of next-generation sequencing and clone-based sequencing in analysis
      of hepatitis B virus reverse transcriptase quasispecies heterogeneity.
AB  - We previously reported that, based on clone-based sequencing (CBS), hepatitis B
      virus (HBV) heterogeneity within the reverse transcriptase (RT) region was a
      predictor of antiviral efficacy. Here, by comparing ultradeep pyrosequencing
      (UDPS), i.e., next-generation sequencing (NGS), with CBS in characterizing the
      genetic heterogeneity of HBV quasispecies within the RT region, we evaluated the
      performance of UDPS in the analysis of HBV viral populations. HBV genomic DNA was
      extracted from serum samples from 31 antiviral treatment-naive patients with
      chronic hepatitis B. The RT region quasispecies were analyzed in parallel using
      CBS and UDPS. Characterization of quasispecies heterogeneity was conducted using
      bioinformatics analysis. Quasispecies complexity values were calculated with the
      formula Sn = -Sigmai(pilnpi)/lnN. The number of qualified strains obtained by
      UDPS was much larger than that obtained by CBS (P < 0.001). Pearson analysis
      showed that there was a positive correlation of quasispecies complexity values at
      the nucleotide level for the two methods (P < 0.05), while the complexity value
      derived from UDPS data was higher than that derived from CBS data (P < 0.001).
      Study of the prevalences of variations within the RT region showed that CBS
      detected an average of 9.7 +/- 1.1 amino acid substitutions/sample and UDPS
      detected an average of 16.2 +/- 1.4 amino acid substitutions/sample. The
      phylogenetic analysis based on UDPS data showed more genetic entities than did
      that based on CBS data. Viral heterogeneity determination by the UDPS technique
      is more sensitive and efficient in terms of low-abundance variation detection and
      quasispecies simulation than that by the CBS method, although imperfect, and thus
      sheds light on the future clinical application of NGS in HBV quasispecies
      studies. 

PMID- 24088860
TI  - Irreproducible and uninterpretable Polymyxin B MICs for Enterobacter cloacae and
      Enterobacter aerogenes.
AB  - Carbapenem-resistant Enterobacter species are emerging nosocomial pathogens. As
      with most multidrug-resistant Gram-negative pathogens, the polymyxins are often
      the only therapeutic option. In this study involving clinical isolates of E.
      cloacae and E. aerogenes, susceptibility testing methods with polymyxin B were
      analyzed. All isolates underwent testing by the broth microdilution (in
      duplicate) and agar dilution (in duplicate) methods, and select isolates were
      examined by the Etest method. Selected isolates were also examined for
      heteroresistance by population analysis profiling. Using a susceptibility
      breakpoint of <=2 MUg/ml, categorical agreement by all four dilution tests (two
      broth microdilution and two agar dilution) was achieved in only 76/114 (67%) of
      E. cloacae isolates (65 susceptible, 11 resistant). Thirty-eight (33%) had either
      conflicting or uninterpretable results (multiple skip wells, i.e., wells that
      exhibit no growth although growth does occur at higher concentrations). Of the 11
      consistently resistant isolates, five had susceptible MICs as determined by
      Etest. Heteroresistant subpopulations were detected in eight of eight isolates
      tested, with greater percentages in isolates with uninterpretable MICs. For E.
      aerogenes, categorical agreement between the four dilution tests was obtained in
      48/56 (86%), with conflicting and/or uninterpretable results in 8/56 (14%). For
      polymyxin susceptibility testing of Enterobacter species, close attention must be
      paid to the presence of multiple skip wells, leading to uninterpretable results.
      Susceptibility also should not be assumed based on the results of a single test.
      Until the clinical relevance of skip wells is defined, interpretation of
      polymyxin susceptibility tests for Enterobacter species should be undertaken with
      extreme caution. 

PMID- 24088861
TI  - Clinical outcomes with rapid detection of methicillin-resistant and methicillin
      susceptible Staphylococcus aureus isolates from routine blood cultures.
AB  - Staphylococcus aureus is a common cause of bacteremia, with a substantial impact
      on morbidity and mortality. Because of increasing rates of methicillin-resistant
      Staphylococcus aureus, vancomycin has become the standard empirical therapy.
      However, beta-lactam antibiotics remain the best treatment choice for methicillin
      susceptible strains. Placing patients quickly on the optimal therapy is one goal
      of antimicrobial stewardship. This retrospective, observational, single-center
      study compared 33 control patients utilizing only traditional full-susceptibility
      methodology to 22 case patients utilizing rapid methodology with CHROMagar medium
      to detect and differentiate methicillin-resistant and methicillin-susceptible
      Staphylococcus aureus strains hours before full susceptibilities were reported.
      The time to targeted therapy was statistically significantly different between
      control patients (mean, 56.5 +/- 13.6 h) and case patients (44.3 +/- 17.9 h) (P =
      0.006). Intensive care unit status, time of day results emerged, and patient age
      did not make a difference in time to targeted therapy, either singly or in
      combination. Neither length of stay (P = 0.61) nor survival (P = 1.0) was
      statistically significantly different. Rapid testing yielded a significant
      result, with a difference of 12.2 h to targeted therapy. However, there is still
      room for improvement, as the difference in time to susceptibility test result
      between the full traditional methodology and CHROMagar was even larger (26.5 h).
      This study supports the hypothesis that rapid testing plays a role in
      antimicrobial stewardship by getting patients on targeted therapy faster. 

PMID- 24088862
TI  - Multicenter evaluation of the Verigene Clostridium difficile nucleic acid assay.
AB  - The Verigene Clostridium difficile Nucleic Acid test (Verigene CDF test)
      (Nanosphere, Northbrook, IL) is a multiplex qualitative PCR assay that utilizes a
      nanoparticle-based array hybridization method to detect C. difficile tcdA and
      tcdB in fecal specimens. In addition, the assay detects binary toxin gene
      sequences and the single base pair deletion at nucleotide 117 (Delta 117) in tcdC
      to provide a presumptive identification of the epidemic strain 027/NAP1/BI
      (referred to here as ribotype 027). This study compared the Verigene CDF test
      with anaerobic direct and enriched toxigenic culture on stool specimens from
      symptomatic patients among five geographically diverse laboratories within the
      United States. The Verigene CDF test was performed according to the
      manufacturer's instructions, and the reference methods performed by a central
      laboratory included direct culture onto cycloserine cefoxitin fructose agar
      (CCFA) and enriched culture using cycloserine cefoxitin mannitol broth with
      taurocholate and lysozyme. Recovered isolates were identified as C. difficile
      using gas liquid chromatography and were tested for toxin using a cell culture
      cytotoxicity neutralization assay. Strains belonging to ribotype 027 were
      determined by PCR ribotyping and bidirectional sequencing for Delta 117 in tcdC.
      A total of 1,875 specimens were evaluable. Of these, 275 specimens (14.7%) were
      culture positive by either direct or enriched culture methods. Compared to direct
      culture alone, the overall sensitivity, specificity, positive predictive value,
      and negative predictive value for the Verigene CDF test were 98.7%, 87.5%, 42%,
      and 99.9%, respectively. Compared to combined direct and enriched culture
      results, the sensitivity, specificity, positive predictive value, and negative
      predictive values of the Verigene CDF test were 90.9%, 92.5%, 67.6%, and 98.3%,
      respectively. Of the 250 concordantly culture-positive specimens, 59 (23.6%) were
      flagged as "hypervirulent"; 53 were confirmed as ribotype 027, and all 59
      possessed Delta 117 in tcdC. Time to results was approximately 2.5 h per
      specimen. The Verigene CDF test is a novel nucleic acid microarray that reliably
      detects both C. difficile toxins A and B in unformed stool specimens and appears
      to adequately identify ribotype 027 isolates. 

PMID- 24088863
TI  - Clinical evaluation of the FilmArray blood culture identification panel in
      identification of bacteria and yeasts from positive blood culture bottles.
AB  - The FilmArray platform (FA; BioFire, Salt Lake City, UT) is a closed diagnostic
      system allowing high-order multiplex PCR analysis with automated readout of
      results directly from positive blood cultures in 1 h. In the present study, we
      evaluated the clinical performance of the FilmArray blood culture identification
      (BCID) panel, which includes 19 bacteria, five yeasts, and three antibiotic
      resistance genes. In total, 206 blood culture bottles were included in the study.
      The FilmArray could identify microorganisms in 153/167 (91.6%) samples with
      monomicrobial growth. Thirteen of the 167 (7.8%) microorganisms were not covered
      by the FilmArray BCID panel. In 6/167 (3.6%) samples, the FilmArray detected an
      additional microorganism compared to blood culture. When polymicrobial growth was
      analyzed, the FilmArray could detect all target microorganisms in 17/24 (71%)
      samples. Twelve blood culture bottles that yielded a positive signal but showed
      no growth were also negative by FilmArray. In 3/206 (1.5%) bottles, the FilmArray
      results were invalid. The results of the FilmArray were reproducible, as
      demonstrated by the testing and retesting of five bottles in the same day and a
      longitudinal follow-up of five other blood cultures up to 4 weeks. The present
      study shows that the FilmArray is a rapid identification method with high
      performance in direct identification of bacteria and yeasts from positive blood
      culture bottles. 

PMID- 24088864
TI  - Validation of the Gen-Probe Aptima qualitative HIV-1 RNA assay for diagnosis of
      human immunodeficiency virus infection in infants.
AB  - The qualitative Roche HIV-1 DNA Amplicor assay has been used for the past 20
      years to diagnose HIV infection in infants and young children but is being phased
      out; hence, alternative assays must be found. The Gen-Probe Aptima qualitative
      HIV-1 RNA assay is currently the only FDA-cleared HIV-1 nucleic acid assay
      approved for diagnosis, but data on the use of this assay with infant plasma are
      limited. We assessed Aptima's performance using control material for
      reproducibility and limit of detection and 394 plasma samples (0.2 to 0.5 ml)
      from HIV-exposed infected and uninfected infants and children for analytical
      sensitivity and specificity. Assays to assess within-run repeatability and
      between-run reproducibility indicated that the controls with 10,000 (5 of 5), 200
      (5 of 5), 100 (16 of 16), 50 (12 of 12), and 25 (20 of 20) HIV-1 RNA copies/ml
      (cp/ml) were always positive, and negatives were always negative (20 of 20). The
      limit of detection was 14 cp/ml, as determined by probit analysis. The analytic
      sensitivity of the assay was 99.5% (189/190 samples; 95% confidence interval
      [CI], 97.1 to 99.9%) and specificity was 99.5% (199/200 samples; 95% CI, 97.2 to
      99.9%). These results suggest that the assay is suitable for early infant
      diagnosis of HIV-1. 

PMID- 24088865
TI  - Analysis of pushing exercises: muscle activity and spine load while contrasting
      techniques on stable surfaces with a labile suspension strap training system.
AB  - Labile surfaces in the form of suspension straps are increasingly being used as a
      tool in resistance training programs. Pushing is a common functional activity of
      daily living and inherently part of a well-rounded training program. This study
      examined pushing exercises performed on stable surfaces and unstable suspension
      straps, specifically muscle activation levels and spine loads were quantified
      together with the influence of employing technique coaching. There were several
      main questions that this study sought to answer: Which exercises challenged
      particular muscles? What was the magnitude of the resulting spine load? How did
      stable and unstable surfaces differ? Did coaching influence the results? Fourteen
      men were recruited as part of a convenience sample (mean age, 21.1 +/- 2.0 years;
      height, 1.77 +/- 0.06 m; mean weight, 74.6 +/- 7.8 kg). Data were processed and
      input to a sophisticated and anatomically detailed 3D model that used muscle
      activity and body segment kinematics to estimate muscle force-in this way, the
      model was sensitive to the individuals choice of motor control for each task;
      muscle forces and linked segment joint loads were used to calculate spine loads.
      Exercises were performed using stable surfaces for hand/feet contact and repeated
      where possible with labile suspension straps. Speed of movement was standardized
      across participants with the use of a metronome for each exercise. There were
      gradations of muscle activity and spine load characteristics to every task. In
      general, the instability associated with the labile exercises required greater
      torso muscle activity than when performed on stable surfaces. Throughout the
      duration of an exercise, there was a range of compression; the TRX push-up ranged
      from 1,653 to 2,128.14 N, whereas the standard push-up had a range from 1,233.75
      to 1,530.06 N. There was no significant effect of exercise on spine compression
      (F(4,60) = 0.86, p = 0.495). Interestingly, a standard push-up showed
      significantly greater shear than TRX angle 1 (p = 0.02), angle 2 (p = 0.01), and
      angle 3 (p = 0.02). As with any training program for the elite or recreational
      athlete alike, specific exercises and programs should reflect one's injury
      history, capabilities, limitations, and training goals. Although none of the
      exercises examined here breached the NIOSH action limit for compression, those
      exercises that produced higher loads should be used relative to the individual.
      Thus, the atlas of muscle activation, compression, and shear forces provided can
      be used to create an appropriate program. Those individuals not able to tolerate
      certain loads may refer to the atlas and choose exercises that minimize load and
      still provide sufficient muscle activation. Conversely, an individual with a
      resilient back that requires an increased muscular challenge may choose exercises
      with higher muscle activation and spine load. This helps the individual, trainer,
      or coach in program design respecting individual differences and training goals.

PMID- 24088866
TI  - Validity of the SenseWear Armband to assess energy expenditure during
      intermittent exercise and recovery in rugby union players.
AB  - Portable wearable devices that assess energy expenditure during intermittent
      exercise and recovery would be useful in team sports. Fourteen state-level male
      rugby union players (mean +/- SD: age, 22 +/- 4 years; body mass, 88.8 +/- 11.2
      kg; height, 1.81 +/- 0.07 m, body fat, 18 +/- 6%) participated in this study.
      Energy expenditure was measured by the SenseWear Armband (SWA) and validated
      against indirect calorimetry as the criterion measure during a 42-minute rugby
      specific intermittent exercise test and an immediate postexercise 10-minute
      recovery period. Energy expenditure measurements from indirect calorimetry and
      the SWA were only moderately correlated during both the exercise test (r = 0.55,
      +/-0.34; mean, +/-90% confidence limits) and recovery period (r = 0.58, +/-0.33).
      The SWA estimate of energy expenditure during exercise was unclear, with a mean
      bias of -1.9% (+/-5.3%), and during recovery energy expenditure was
      overestimated, with a mean bias of 17% (+/-12%) at the mean estimated energy
      expenditure. Typical error of SWA energy expenditure estimates expressed as a
      coefficient of variation (+/-90% confidence interval) was 10% (8-16%) during
      exercise and 19% (14-30%) during recovery. The SWA did not provide a valid
      measure of energy expenditure during rugby-specific intermittent exercise or 10
      minute postexercise recovery. Further improvements are required in the
      performance of the SWA before it can be used routinely in intermittent sports and
      provide worthwhile information in relation to workloads of athletes for sport
      scientists and coaches.

PMID- 24088867
TI  - Plyometric training performance in elite-oriented prepubertal female gymnasts.
AB  - We studied the effectiveness of a combined strength and plyometric training
      program (experimental period) on jumping performance when compared with a
      training routine on apparatus (control period) over 2 successive gymnastics
      training seasons. Nine female elite-orientated gymnasts (around 30-hour training
      per week) were participated in the study. The study was based on a 20-month
      longitudinal design covering 2 training seasons separated by a competitive period
      and transition periods. Each season included 1 control and 1 experimental period
      (CtrlDelta1 + ExDelta1 and CtrlDelta2 + ExDelta2, respectively). Before and after
      each control and experimental period, we assessed plyometric performance by means
      of drop jumps (DJs) from 20, 40, 60, 80, and 100 cm. The jump performance
      variables considered were flight time (FT), contact time (CT), flight-contact
      ratio (FC), and estimated mechanical power (also called Bosco expression [BE]),
      all of which were expressed as raw data and normalized (expressed as a
      percentage) with respect to the recordings at the beginning of each period of
      analysis. Flight time was the only variable to increase not only during both
      experimental periods but also during both controls. Our results confirmed larger
      relative increments of all the variables (FT, CT, BE, and FC), except for CT at
      DJs of 80 and 100 cm, during the experimental periods than during their
      respective previous control periods. Despite the additive effect of growth,
      development, and maturation, the gymnasts were not able to maintain the DJ
      performance accomplished during ExDelta1, thereby confirming detraining during
      the competitive and transition periods. We conclude that a combination of heavy
      resistance training with high impact plyometric jumps is effective in prepubertal
      gymnasts, despite their initial high level of physical conditioning.

PMID- 24088868
TI  - Anthropogenic noise causes body malformations and delays development in marine
      larvae.
AB  - Understanding the impact of noise on marine fauna at the population level
      requires knowledge about the vulnerability of different life-stages. Here we
      provide the first evidence that noise exposure during larval development produces
      body malformations in marine invertebrates. Scallop larvae exposed to playbacks
      of seismic pulses showed significant developmental delays and 46% developed body
      abnormalities. Similar effects were observed in all independent samples exposed
      to noise while no malformations were found in the control groups (4881 larvae
      examined). Malformations appeared in the D-veliger larval phase, perhaps due to
      the cumulative exposure attained by this stage or to a greater vulnerability of D
      veliger to sound-mediated physiological or mechanical stress. Such strong impacts
      suggest that abnormalities and growth delays may also result from lower sound
      levels or discrete exposures during the D-stage, increasing the potential for
      routinely-occurring anthropogenic noise sources to affect recruitment of wild
      scallop larvae in natural stocks. 

PMID- 24088871
TI  - How ecological restoration alters ecosystem services: an analysis of carbon
      sequestration in China's Loess Plateau.
AB  - Restoring disturbed and over-exploited ecosystems is important to mitigate human
      pressures on natural ecosystems. China has launched an ambitious national
      ecosystem restoration program called Grain to Green Program (GTGP) over the last
      decade. By using remote sensing techniques and ecosystem modelling, we
      quantitatively evaluated the changes in ecosystem carbon sequestration since
      China's GTGP program during period of 2000-2008. It was found the NPP and NEP in
      this region had steadily increased after the initiative of the GTGP program, and
      a total of 96.1 Tg of additional carbon had been sequestered during that period.
      Changes in soil carbon storage were lagged behind and thus insignificant over the
      period, but was expected to follow in the coming decades. As a result, the Loess
      Plateau ecosystem had shifted from a net carbon source in 2000 to a net carbon
      sink in 2008. The carbon sequestration efficiency was constrained by
      precipitation, and appropriate choices of restoration types (trees, shrubs, and
      grasses) in accordance to local climate are critical for achieving the best
      benefit/cost efficiency. 

PMID- 24088869
TI  - Miz1 is required to maintain autophagic flux.
AB  - Miz1 is a zinc finger protein that regulates the expression of cell cycle
      inhibitors as part of a complex with Myc. Cell cycle-independent functions of
      Miz1 are poorly understood. Here we use a Nestin-Cre transgene to delete an
      essential domain of Miz1 in the central nervous system (Miz1(DeltaPOZNes)).
      Miz1(DeltaPOZNes) mice display cerebellar neurodegeneration characterized by the
      progressive loss of Purkinje cells. Chromatin immunoprecipitation sequencing and
      biochemical analyses show that Miz1 activates transcription upon binding to a non
      palindromic sequence present in core promoters. Target genes of Miz1 encode
      regulators of autophagy and proteins involved in vesicular transport that are
      required for autophagy. Miz1(DeltaPOZ) neuronal progenitors and fibroblasts show
      reduced autophagic flux. Consistently, polyubiquitinated proteins and p62/Sqtm1
      accumulate in the cerebella of Miz1(DeltaPOZNes) mice, characteristic features of
      defective autophagy. Our data suggest that Miz1 may link cell growth and ribosome
      biogenesis to the transcriptional regulation of vesicular transport and
      autophagy.

PMID- 24088872
TI  - Complexation of a pentiptycene-derived trans-bis(crown ether) host with different
      terminally functionalized paraquat derivatives in solution and the solid state: a
      switchable complexation process controlled by potassium ions.
AB  - The complexation behaviour of a pentiptycene-derived bis(crown ether), containing
      two 24-crown-8 moieties in a trans arrangement, and a series of paraquat
      derivatives with different terminal functional groups was investigated. It was
      found that all of the paraquat derivatives could form stable 2 : 1 complexes with
      the pentiptycene-derived host both in solution and the solid state, where
      multiple non-covalent interactions between the host and the guests played an
      important role. Moreover, the binding and release of the guests in the complexes
      could also be efficiently controlled by the removal and addition of potassium
      ions.

PMID- 24088870
TI  - Intravenous hemostats: challenges in translation to patients.
AB  - Excessive bleeding and the resulting complications are a leading killer of young
      people globally. There are many successful methods to halt bleeding in the
      extremities, including compression, tourniquets, and dressings. However, current
      treatments for internal hemorrhage (including from head or truncal injuries),
      termed non-compressible bleeding, are inadequate. For these non-compressible
      injuries, blood transfusions are the current treatment standard. However, they
      must be refrigerated, may potentially transfer disease, and are of limited
      supply. In addition, time is of the essence for halting hemorrhage, since more
      than a third of civilian deaths due to hemorrhage from trauma occur before the
      patient even reaches the hospital. As a result, particles that can cross-link
      activated platelets through the glycoprotein IIb/IIIa receptor expressed on
      activated platelets are being investigated as an alternative treatment for non
      compressible bleeding. Ideally, these particles would interact specifically with
      platelets to stabilize the platelet plug. Initial designs used biologically
      derived microparticles with red blood cell fragment or albumin cores decorated
      with RGD or fibrinogen, which bind to GPIIb/IIIa. More recently there has been
      research into the use of fully synthetic nanoparticles with liposomal or polymer
      cores that crosslink platelets through a targeting peptide bound to the surface.
      Some of the challenges for the development of these particles include appropriate
      sizing to prevent blocking the capillaries of the lungs, immune system evasion to
      prevent strong reactions and increase circulation time, and storage and
      resuspension so that first responders can easily use the particles. In addition,
      the effectiveness of the variety of animal bleeding models in predicting outcomes
      must be examined before test results can be fully understood. Progress has been
      made in the development of particles to combat hemorrhage, but issues of immune
      sensitivity and storage must be resolved before these types of particles can be
      translated for human use. 

PMID- 24088874
TI  - From the editor.

PMID- 24088873
TI  - Comparison of multiple red cell volume methods performed concurrently in
      premature infants following allogeneic transfusion.
AB  - BACKGROUND: Study of the pathophysiology and treatment of anemia of prematurity
      is facilitated by direct measurement of red cell volume (RCV) utilizing
      microliter quantities of blood samples. Our objective was to compare concurrent
      measurements of multiple direct RCV methods in infants. METHODS: Eighteen preterm
      infants receiving clinically indicated transfusions had concurrent flow
      cytometric determinations of RCV and 24-h red blood cell (RBC) recovery based on
      donor-recipient differences of biotin-labeled RBCs (BioRBCs), Kidd antigen
      mismatched RBCs, and fetal hemoglobin-positive (HbF(+)) RBCs. High-performance
      liquid chromatography (HPLC) was also used for measuring HbF and adult hemoglobin
      protein concentrations for the determination of RCV. RESULTS: Concurrent RCV
      measurements using BioRBCs (18 and 54 ug/ml), Kidd antigen, and HbF flow
      cytometry were not statistically different compared with RCVs measured using the
      reference BioRBC density (6 ug/ml). By contrast, the HbF-HPLC method
      overestimated RCV by 45% compared with the reference method. All the methods
      demonstrated 100% 24-h posttransfusion RBC recovery (PTR24). CONCLUSION: Because
      BioRBC, Kidd antigen, and fetal hemoglobin (HbF) flow cytometry are safe and
      accurate methods requiring <10 ul of patient blood for determining RCV and PTR24
      in preterm infants, they can be useful in clinical and research studies of anemia
      and other conditions.

PMID- 24088875
TI  - Effect of modest pay-for-performance financial incentive on time-to-discharge
      summary dictation among medical residents.
AB  - OBJECTIVE: Evaluate the effect of a modest financial incentive on time-to
      discharge summary dictation among medicine residents. BACKGROUND: Pay-for
      performance incentives are used in a number of health care settings. Studies are
      lacking on their use with medical residents and other trainees. Timely completion
      of discharge summaries is necessary for effective follow-up after
      hospitalization, and residents perform the majority of discharge summary
      dictations in academic medical centers. METHODS: Medicine residents with the
      lowest average discharge-to-dictation time during their 1-month inpatient
      medicine ward rotation were rewarded with a $50 gift card. Discharge data were
      captured using an autopopulating electronic database. RESULTS: The average
      discharge-to-dictation time was reduced from 7.44 to 1.84 days, representing a
      75.3% decrease. Almost 90% of discharge summary dictations were performed on the
      day of discharge. CONCLUSION: A modest financial incentive resulted in a marked
      improvement in the time-to-discharge summary dictation by medicine residents. Pay
      for-performance programs may be an effective strategy for improving the quality
      and efficiency of patient care in academic medical centers.

PMID- 24088877
TI  - Motivators and hygiene factors among physicians responding to explicit incentives
      to improve the value of care.
AB  - BACKGROUND: Physician's dissatisfaction is reported to be increasing, especially
      in primary care. The transition from fee-for-service to outcome-based
      reimbursements may make matters worse. PURPOSE/OBJECTIVE: To investigate
      influences of provider attitudes and practice settings on job
      satisfaction/dissatisfaction during transition to quality-based payment models,
      we assessed self-reported satisfaction/dissatisfaction with practice in a
      Rochester (New York)-area physician practice association in the process of
      implementing pay-for-performance. SUBJECTS/METHODS: We linked cross-sectional
      data for 215 survey respondents on satisfaction ratings and behavioral attitudes
      with medical record data on their clinical behavior and practices, and census
      data on their catchment population. Factors associated with the odds of being
      satisfied or dissatisfied were determined via predictive multivariable logistic
      regression modeling. RESULTS/CONCLUSIONS: Dissatisfied physicians were more
      likely to have larger-than-average patient panels, lower autonomy and/or control,
      and beliefs that quality incentives were hindering patient care. Satisfied
      physicians were more likely to have a higher sense of autonomy and control,
      smaller patient volumes, and a less complex patient mix. Efforts to maintain or
      improve satisfaction among physicians should focus on encouraging professional
      autonomy during transitions from volume-based to quality/outcomes-based payment
      systems. An optimum balance between accountability and autonomy/control might
      maximize both health care quality and job satisfaction.

PMID- 24088878
TI  - Improving patient access in nuclear medicine: a case study of PET scanner
      scheduling.
AB  - We used the systems engineering technique of discrete event simulation modeling
      to assist in increasing patient access to positron emission tomographic
      examinations in the Department of Nuclear Medicine at Mayo Clinic, Rochester. The
      model was used to determine the best universal slot length to address the
      specific access challenges of a destination medical center such as Mayo Clinic.
      On the basis of the modeling, a new schedule was implemented in April 2012 and
      our before and after data analysis shows an increase of 2.4 scans per day. This
      was achieved without requiring additional resources or negatively affecting
      patient waiting, staff satisfaction (as evaluated by day length), or examination
      quality. 

PMID- 24088879
TI  - The structure of service quality perceptions for multiple-encounter services.
AB  - OBJECTIVE: The objective of this study was to examine a complex service
      environment-hospitals-to suggest how service quality could be reframed and
      measured for multiple-encounter service situations more effectively. SUBJECTS: In
      this cross-sectional study, a sample of 371 patients completed the survey
      instrument. Service quality measures were guided by the literature but allowed to
      flow from the respondents at the preliminary stage. METHODS: Confirmatory factor
      analysis, along with structural equation modeling, was used to test the
      hypothesized relationships among key actors' performance metrics (KAPMs).
      RESULTS: Patient satisfaction is significantly influenced by perceived service
      quality based on KAPMs. For multiple-encounter services, service quality
      dimensions and measures ought to be tied to KAPMs. CONCLUSIONS: Primary actors
      ie, doctors-need knowledge and skills about patient psychology, negotiation,
      handling difficult patients, and, importantly, "putting the customer first."
      Sensitivity training on such matters should be provided. The secondary actors are
      the nurses who have more frequent contact with the patients. Nurses need to be
      perceived as "patient advocates." Effective advocacy begins with prompt and
      caring services to build trust. The tertiary actors in their support role also
      ought to be integrated into becoming vital part of the service provided.

PMID- 24088880
TI  - An exploratory analysis of the correlation of pain scores, patient satisfaction
      with relief from pain, and a new measure of pain control on the total dose of
      opioids in pain care.
AB  - OBJECTIVE: We explored the associations between opioid dose and multiple measures
      of pain. STUDY DESIGN AND MEASURES: Thirty-two consecutive patients admitted
      solely for an acute exacerbation of cancer-related pain or for surgery were
      followed for their entire hospital stay (115 days of pain). For each hospital
      day, we collected pain scores, the number of pain scores, trends in pain scores,
      the percentage of time patients had 100% acceptable relief from pain, and the
      number of times patients were asked about acceptable pain relief. Finally, we
      asked those who had 100% relief of pain whether they could have used more pain
      medicine. Linear regression models were fit to estimate the amount of variation
      explained (R) in dose of medication, by each pain measurement variable. RESULTS:
      Nineteen patients with cancer (74 days of pain) and 13 patients undergoing
      surgery (41 days of pain) were evaluated. Pain scores, the number of pain scores,
      trends in pain scores, and 100% acceptable relief scores poorly correlated with
      the use of medication in the linear regression models (R for all models <=0.2). A
      question about needing more pain medicine explained the greatest amount of
      variation in opioid dose. CONCLUSIONS: Pain and acceptable relief scores do not
      adequately reflect the use of medication. A prospective study is needed to
      further assess the value of additional measures of the adequacy of pain care.

PMID- 24088881
TI  - Medical home interventions and quality outcomes for older adults: a systematic
      review.
AB  - PURPOSE: Medical home care has been identified as a model for improving primary
      care delivery and population-specific quality and safety outcomes. Questions
      remain how this model affects older adult quality. This systematic review
      addresses 2 important questions: Are quality and safety outcomes associated with
      medical home and patient-centered interventions, and how is quality studied in
      older adult primary care research? METHODS: The authors searched MEDLINE for
      articles that examined interventions that were associated with medical home
      principles. Each article was evaluated using a standardized data abstraction
      form. Studies were categorized according to how interventions influenced specific
      quality and safety outcomes-improved clinical and treatment measures and care
      delivery processes-for older adults. RESULTS: Thirteen research studies were
      identified by the authors. A great deal of variety exists in both research design
      and how quality and safety outcomes for older adults are operationalized in
      primary care. In general, studies indicate potentially beneficial relationships
      between 3 types of medical home interventions targeting health care utilization,
      disease management, and patient-provider communication to improved quality
      outcomes. CONCLUSION: It would be advantageous for practices looking to align
      with patient-centered medical home quality and safety goals to consider the needs
      of older adults when redesigning care delivery.

PMID- 24088884
TI  - Why have a quality management program?

PMID- 24088885
TI  - Outcomes measures and risk adjustment.

PMID- 24088886
TI  - Clinical error management.

PMID- 24088887
TI  - Quality management system in a private practice setting.

PMID- 24088888
TI  - The evolution of checklists and implications for anesthesiology.

PMID- 24088890
TI  - Using data in future models of anesthesia care.

PMID- 24088889
TI  - Ensuring safety in the operating room: the "fundamental use of surgical energy"
      (FUSE) program.

PMID- 24088892
TI  - Preface: quality management in anesthesiology, volume 1: fundamentals.

PMID- 24088893
TI  - AICAR stimulation metabolome widely mimics electrical contraction in isolated rat
      epitrochlearis muscle.
AB  - Physical exercise has potent therapeutic and preventive effects against metabolic
      disorders. A number of studies have suggested that 5'-AMP-activated protein
      kinase (AMPK) plays a pivotal role in regulating carbohydrate and lipid
      metabolism in contracting skeletal muscles, while several genetically manipulated
      animal models revealed the significance of AMPK-independent pathways. To
      elucidate significance of AMPK and AMPK-independent signals in contracting
      skeletal muscles, we conducted a metabolomic analysis that compared the metabolic
      effects of 5-aminoimidazole-4-carboxamide-1-beta-D-ribonucleoside (AICAR)
      stimulation with the electrical contraction ex vivo in isolated rat
      epitrochlearis muscles, in which both alpha1- and alpha2-isoforms of AMPK and
      glucose uptake were equally activated. The metabolomic analysis using capillary
      electrophoresis time-of-flight mass spectrometry detected 184 peaks and
      successfully annotated 132 small molecules. AICAR stimulation exhibited high
      similarity to the electrical contraction in overall metabolites. Principal
      component analysis (PCA) demonstrated that the major principal component
      characterized common effects whereas the minor principal component distinguished
      the difference. PCA and a factor analysis suggested a substantial change in redox
      status as a result of AMPK activation. We also found a decrease in reduced
      glutathione levels in both AICAR-stimulated and contracting muscles. The muscle
      contraction-evoked influences related to the metabolism of amino acids, in
      particular, aspartate, alanine, or lysine, are supposed to be independent of AMPK
      activation. Our results substantiate the significance of AMPK activation in
      contracting skeletal muscles and provide novel evidence that AICAR stimulation
      closely mimics the metabolomic changes in the contracting skeletal muscles.

PMID- 24088894
TI  - Calmodulin-dependent binding to the NHE1 cytosolic tail mediates activation of
      the Na+/H+ exchanger by Ca2+ and endothelin.
AB  - The mammalian Na(+)/H(+) exchanger isoform 1 (NHE1) is a ubiquitous plasma
      membrane protein that regulates intracellular pH by removing a single proton
      (H(+)) in exchange for one extracellular Na(+). The human protein contains a ~500
      amino acid membrane domain and a regulatory, ~315-amino acid cytosolic domain.
      NHE1 is activated by a number of hormones including endothelin (ET) and by
      Ca(2+). The regulatory tail possesses an inhibitory calmodulin (CaM)-binding
      domain, and inhibition of NHE1 is relieved by binding of a Ca(2+)-CaM complex. We
      examined the dynamics of ET-1 and Ca(2+) regulation of binding to NHE1 in vivo.
      CFP was linked to the NHE1 protein cytoplasmic COOH terminus. This was stably
      transfected into AP-1 cells that are devoid of their own NHE1 protein. The
      protein was expressed and targeted properly and retained NHE1 activity comparable
      to the wild-type protein. We examined the in vivo coupling of NHE1 to CaM by
      Forster resonance energy transfer using CaM linked to the fluorescent protein
      Venus. CaM interaction with NHE1 was dynamic. Removal of serum reduced CaM
      interaction with NHE1. Addition of the Ca(2+) ionophore ionomycin increased the
      interaction between CaM and NHE1. We expressed an ET receptor in AP-1 cells and
      also found a time-dependent association of NHE1 with CaM in vivo that was
      dependent on ET treatment. The results are the first demonstration of the in vivo
      association of NHE1 and CaM through ET-dependent signaling pathways. 

PMID- 24088895
TI  - Activin A induction of erythroid differentiation sensitizes K562 chronic myeloid
      leukemia cells to a subtoxic concentration of imatinib.
AB  - Chronic myeloid leukemia (CML) is a hematopoietic stem/progenitor cell disorder
      in which Bcr-Abl oncoprotein inhibits cell differentiation. Differentiation
      induction is considered an alternative strategy for treating CML. Activin A, a
      member of the transforming growth factor-beta superfamily, induces erythroid
      differentiation of CML cells through the p38 MAPK pathway. In this study,
      treatment of the K562 CML stem/progenitor cell line with activin A followed by a
      subtoxic concentration of the Bcr-Abl inhibitor imatinib strongly induced growth
      inhibition and apoptosis compared with simultaneous treatment with activin A and
      imatinib. Imatinib-induced growth inhibition and apoptosis following activin A
      pretreatment were dose- and time-dependent. Imatinib-induced growth inhibition
      and apoptosis were also dependent on the pretreatment dose of activin A. More
      than 90% of the activin A-induced increases in glycophorin A-positive cells were
      sensitive to imatinib. However, only some of original glycophorin A-positive
      cells in the activin A treatment group were sensitive to imatinib. Sequential
      treatment with activin A and imatinib decreased Bcr-Abl, procaspase-3, Mcl-1, and
      Bcl-xL and also induced cleavage of procaspase-3/poly(ADP-ribose)polymerase. The
      reduction of erythroid differentiation in p38 MAPK dominant-negative mutants or
      by short hairpin RNA knockdown of p38 MAPK decreased the growth inhibition and
      apoptosis mediated by sequential treatment with activin A and imatinib.
      Furthermore, the same inhibition level of multidrug resistance 1 expression was
      observed in cells treated with activin A alone, treated sequentially with activin
      A and imatinib, or treated simultaneously with activin A and imatinib. The p38
      MAPK inhibitor SB-203580 can restore activin A-inhibited multidrug resistance 1
      expression. Taken together, our results suggest that a subtoxic concentration of
      imatinib could exhibit strong cytotoxicity against erythroid-differentiated K562
      CML cells. 

PMID- 24088897
TI  - Unmixing the NMR spectra of similar species - vive la difference.
AB  - Diffusion-ordered spectroscopy (DOSY) is one of the most powerful methods for
      intact mixture analysis by NMR. However, the separation of overlapped spectra by
      current DOSY methods typically requires a minimum of 30% difference in diffusion
      coefficient. Here we present a new algorithm (OUTSCORE) that can improve the
      situation by almost an order of magnitude, allowing the unmixing of severely
      overlapped species of similar size, by combining least squares fitting with cross
      talk minimisation, maximising spectral difference. 

PMID- 24088896
TI  - Cyp1B1 expression promotes angiogenesis by suppressing NF-kappaB activity.
AB  - Nuclear factor-kappaB (NF-kappaB) is a master regulator of genes that control a
      large number of cellular processes, including angiogenesis and inflammation. We
      recently demonstrated that cytochrome P-450 1B1 (Cyp1B1) deficiency in
      endothelial cells (EC) and pericytes (PC) results in increased oxidative stress,
      alterations in migration, attenuation of capillary morphogenesis, sustained
      activation of NF-kappaB, and increased expression of thrombospondin-2 (TSP2), an
      endogenous inhibitor of angiogenesis. On the basis of a growing body of evidence
      that phenethyl isothiocyanate (PEITC) and pyrrolidine dithiocarbamate (PDTC)
      function as antioxidants and suppressors of NF-kappaB activation, we investigated
      their potential ability to restore a normal phenotype in Cyp1B1-deficient
      (cyp1b1(-/-)) vascular cells. PEITC and PDTC inhibited NF-kappaB activity and
      expression in cyp1b1(-/-) EC and PC. We also observed restoration of migration
      and capillary morphogenesis of cyp1b1(-/-) EC and decreased cellular oxidative
      stress in cyp1b1(-/-) EC and PC without restoration to normal TSP2 levels. In
      addition, expression of a dominant-negative inhibitor kappaBalpha, a suppressor
      of NF-kappaB activation, decreased NF-kappaB activity without affecting TSP2
      expression in these cells. In contrast, knockdown of TSP2 expression resulted in
      attenuation of NF-kappaB activity in cyp1b1(-/-) vascular cells. Furthermore,
      expression of TSP2 in wild-type (cyp1b1(+/+)) cells resulted in increased NF
      kappaB activity. Together, our results demonstrate an important role for TSP2 in
      modulation of NF-kappaB activity and attenuation of angiogenesis. Thus Cyp1B1
      expression in vascular cells plays an important role in the regulation of
      vascular homeostasis through modulation of the cellular reductive state, TSP2
      expression, and NF-kappaB activation. 

PMID- 24088898
TI  - Surgical site infection monitoring: are 2 systems better than 1?

PMID- 24088899
TI  - Cholesterol regulation of ion channels: crosstalk in proteins, crosstalk in
      lipids.

PMID- 24088900
TI  - High rates of false-positive hepatitis C antibody tests can occur after left
      ventricular assist device implantation.
AB  - Hepatitis C virus (HCV) screening is routine before cardiac transplantation, and
      virus presence is an exclusion at most centers. Left ventricular assist devices
      (LVADs) are often used as a bridge to transplantation and cause immune
      activation. We collected data on 32 consecutive patients undergoing LVAD
      placement between January 2006 and February 2008 at a single center. Of the 23
      potential bridge-to-transplant patients with HCV testing before and after LVAD,
      seven (30%) turned positive for HCV antibody but did not have true HCV infection
      on confirmatory testing. Cardiac transplant care providers should be aware of
      possible false-positive HCV antibody tests in this setting. 

PMID- 24088901
TI  - A fast building and effective hydraulic pediatric mock circulatory system for the
      evaluation of a left ventricular assist device.
AB  - A mock circulatory system (MCS) has been proven a useful tool in the development
      of a ventricular assist device. Nowadays a MCS aimed at the evaluation of
      pediatric blood pumps, which require many different considerations compared with
      that of adults, has become an urgent need. This article presents the details on
      how the dynamic process of the left ventricle, which is described in terms of the
      pressure-volume loop (P-V loop), and the properties of the circulation such as
      compliance and resistance are simulated by hydraulic elements. A simple control
      method is introduced to reproduce the physiological afterload and preload
      sensitivities of the mock ventricle for the first time. Hemodynamic performance
      of the system is obtained by medical sensors to validate the similarity of the
      device to the native cardiovascular system. The actual sensitivities of the mock
      ventricle are obtained intuitively from the changes of the P-V loops. The aortic
      input impedance of the MCS is also obtained and compared with the data from
      previous medical reports. At last a pediatric left ventricular assist device
      (LVAD) prototype is introduced for testing to further verify the effectiveness of
      the MCS. The experimental results indicate that this pediatric MCS is capable of
      reproducing basic hemodynamic characteristics of a child in both normal and
      pathological conditions and it is sufficient for testing a pediatric LVAD.
      Besides, most components constituting the main hydraulic part of this MCS are
      inexpensive off-the-shelf products, making the MCS easy and fast to build. 

PMID- 24088902
TI  - Timing of temporary right ventricular assist device insertion for severe right
      heart failure after left ventricular assist device implantation.
AB  - Data on how the timing of a temporary right ventricular assist device (RVAD)
      insertion affects outcome are limited in patients receiving left ventricular
      assist device (LVAD). Of the 282 patients who underwent LVAD placement between
      January 2000 and November 2010, 40 (14%) required concomitant (n = 26) or delayed
      (n = 14) RVAD insertion as temporary support. We analyzed early and 1-year
      outcomes. Preoperative variables were similar in the concomitant and delayed RVAD
      groups. The hospital mortality rate was approximately 50% in both groups (p =
      0.82). The 1-year actuarial survival was similar in both groups (p = 0.42).
      Patients who required RVAD support had higher in-hospital mortality and worse 1
      year survival rates than those who received LVAD only (48% vs. 9.5%, p < 0.0001;
      40% vs. 82%, p < 0.0001). Multivariate logistic regression analysis indicated
      RVAD use as a significant risk factor for 1-year mortality (odds ratio, 18; p =
      0.0003; 95% confidence interval, 3.765-86.74). Timing of temporary RVAD insertion
      did not affect overall survival. Necessity of RVAD support is associated with
      significantly worse early and late mortality at any rate. The decision to place
      the RVAD can be made once it is clinically necessary. 

PMID- 24088903
TI  - Sedation practice in veno-venous extracorporeal membrane oxygenation: an
      international survey.
AB  - Sedation practice in extracorporeal membrane oxygenation (ECMO) is challenging,
      and some studies suggest that pharmacokinetics of sedative drugs are altered by
      the circuitry components. We conducted an international survey of sedation
      practice in centers offering veno-venous ECMO for adult patients in collaboration
      with the Extracorporeal Life Support Organization. A total 102 respondents
      participated representing various experienced centers from around the world.
      Fifty-eight percent responded that patients on ECMO have a higher or much higher
      sedation requirement than other critically ill patients, whilst 51% achieved a
      responsive or cooperative level of sedation. Midazolam (79%), morphine (43%) and
      fentanyl (45%) were most frequently used. Alpha-2 agonists were prescribed in 66%
      while propofol was used infrequently (36%). Thirty-five percent did not use
      continuous muscle relaxants. Responses from experienced users differed to those
      who reported less experience. Sedation practice in ECMO varies widely.
      Cooperative or responsive levels of sedation can frequently be achieved, and the
      drugs used differ from those used in non-ECMO patients. 

PMID- 24088904
TI  - VADoscopy: a novel intraoperative technique to evaluate HeartMate II left
      ventricular assist device inflow obstruction and thrombosis.
AB  - With HeartMate II (HMII) implants increasing so has the frequency of device
      exchange. However, identifying inflow cannula obstruction, pump thrombosis, or
      outflow obstruction as the mechanism of pump dysfunction can be difficult.
      Echocardiography, CT angiogram, and cardiac catheterization are not definitive in
      determining the location of pump failure. Therefore, intraoperative examination
      is often necessary to confirm a diagnosis, requiring extensive dissection to
      visualize the entire system. We hypothesized a novel intraoperative technique,
      VADoscopy, can evaluate the inflow cannula for thrombus or pannus formation, and
      can help guide decision on which portion(s) of the HMII require replacement.
      Visualization of the inflow cannula can determine if either the pump itself or
      the pump along with the inflow cannula requires replacement, potentially limiting
      unnecessary dissection around the left ventricular apex and inflow cannula. A
      subxiphoid or subcostal incision exposes the pump. Patients are placed on
      cardiopulmonary bypass using the femoral vein and artery, after the outflow
      cannula is clamped. Once the pump is removed from the pocket, a 22 French 80
      cm(Edwards Life Science, Irvine, CA) Fogarty balloon is advanced through the
      inflow cannula into the left ventricle and inflated to limit blood flow from the
      heart. A 5 French 30 cm flexible endoscope (Karl Starz Flex-X, Germany) is then
      placed into the inflow cannula and left ventricle to evaluate for the presence of
      thrombus, pannus, or debris. Six patients had HMII exchange with VADoscopy. In
      all patients, VADoscopy demonstrated no inflow cannula pannus or thrombus as the
      cause of pump dysfunction. Postoperatively there were no embolic events or
      evidence of reoccurring pump dysfunction suggesting an inflow cannula obstruction
      was not missed. VADoscopy is a novel and effective operative diagnostic modality
      to evaluate the inflow cannula within the HMII left ventricular assist device,
      limiting the amount of dissection, and potentially reducing the morbidity
      associated with HMII pump exchange. 

PMID- 24088905
TI  - Which is better: a miniaturized percutaneous ventricular assist device or
      extracorporeal membrane oxygenation for patients with cardiogenic shock?
AB  - The purpose of this study is to compare outcomes associated with the use of
      Impella and TandemHeart short-term support devices with venoarterial
      extracorporeal membrane oxygenation (ECMO) therapy for postinfarction- or
      decompensated cardiomyopathy-related cardiogenic shock. Between January 2006 and
      September 2011, 79 patients were supported with either an Impella axial flow pump
      (n = 7) or a TandemHeart centrifugal pump (n = 11), or with ECMO (n = 61) therapy
      for cardiogenic shock in a single institution. Pertinent variables and
      postprocedural events were analyzed in this cohort of patients using a
      prospectively maintained clinical database. The in-hospital mortality, successful
      weaning from mechanical circulatory support, bridge to long-term destination
      support device and heart transplantation, and limb complications did not differ
      between the 2 groups based on intention-to-treat analysis. Age was the only
      independent predictor for in-hospital survival. In this cohort of patients, short
      term support devices and ECMO achieved comparable results. In the modern era of
      medical cost restraints, ECMO may be more cost effective for patients with
      postinfarction- or decompensated cardiomyopathy-related cardiogenic shock. Larger
      randomized trials may be necessary to further elucidate this topic. 

PMID- 24088906
TI  - Surgical resection of a solitary plasmacytoma originating in a rib.
AB  - Plasma cell neoplasms can present as a single lesion (solitary plasmacytoma) or
      as multiple lesions (multiple myeloma). Solitary plasmacytoma is a rare plasma
      cell neoplasm. There are 2 separate entities, dependent on the location of the
      lesion originating in either bone or extramedullary soft tissue. It is defined as
      a proliferation of monoclonal plasma cells without evidence of significant bone
      marrow plasma-cell infiltration. We present a 71-year-old woman who was diagnosed
      with a solitary plasmacytoma of the bone located in the right third rib after
      surgical resection. A chest roentgenogram showed a solitary expanding lesion in
      the right third rib. Chest computed tomography (CT) revealed an osteolytic chest
      wall tumor. Fluorodeoxyglucose positron emission tomography and CT (PET-CT)
      showed no abnormal uptake in the whole body, except for the third rib lesion. The
      patient underwent complete en-bloc resection of the chest wall including ribs,
      muscle, and parietal pleura. The patient is asymptomatic without any recurrence
      after one and a half years of follow up. 

PMID- 24088907
TI  - Right main pulmonary artery thrombus after type a aortic dissection repair.
AB  - Type A aortic dissection involves the ascending thoracic aorta and needs emergent
      surgical repair since these patients are at increased risk of complications such
      as aortic rupture, aortic regurgitation, myocardial infarction, and cardiac
      tamponade. We describe two cases of right main pulmonary artery thrombus after
      Type A aortic dissection repair with graft. The right main pulmonary artery
      thrombus is a very rare complication of Type A aortic dissection repair and has
      never been reported up to the present time. The preferred location of thrombus
      after ascending aortic dissection repair is the right main pulmonary artery due
      to its close approximation. The possible mechanism of right main pulmonary artery
      thrombus is the compression of the right main pulmonary artery by distorted
      aortic structure after the surgery and altered blood flow dynamics in the
      pulmonary artery. 

PMID- 24088908
TI  - An extremely elderly patient with lung cancer who underwent surgery.
AB  - We report the case of an extremely elderly patient with long-term survival after
      surgical resection for lung cancer. A 93-year-old man was evaluated for an
      abnormal density on chest radiography. Chest computed tomography (CT) showed a
      nodular density of 2.5 * 2.5 cm in the left S4b segment. Lung cancer was
      diagnosed by bronchoscopy, and left posterolateral thoracotomy and S4
      segmentectomy were performed. Group 1 lymph node dissection and sampling of the
      6th lymph node were also performed. Pathological examination revealed poorly
      differentiated squamous cell carcinoma without any lymph node metastases. The
      tumor was staged as p-T1aN0M0 stage IA. No complications were encountered
      postoperatively, and the patient was discharged. He remains alive as of 5 years
      postoperatively without any recurrence. 

PMID- 24088909
TI  - Simultaneous aortic valve replacement and pectus excavatum correction in a 76
      year-old man.
AB  - A 76-year-old man was admitted to our department to undergo surgical treatment
      for aortic valve regurgitation. On physical examination, a bowl-shaped concavity
      was noted. Chest computed tomography revealed left-sided heart displacement by
      severe pectus excavatum with a Haller index of 6.40. Considering the
      postoperative cardiopulmonary complications that may result from mechanical
      compression due to uncorrected sternal deformities, we decided to perform a
      simultaneous aortic valve replacement and pectus excavatum correction. The
      operation time was long (570 min) and involved a high-volume transfusion due to
      excessive bleeding caused by resection of the deformed costal cartilages and
      sternal osteotomy under the use of heparin. The endotracheal tube was removed on
      the fifth postoperative day, but reintubation was required because of hypercapnea
      and difficulty in sputum discharge. With the aid of tube feeding for nutritional
      management, his cardiopulmonary function gradually ameliorated and his general
      condition improved. Consequently, he was weaned from mechanical ventilation on
      the 14th postoperative day. The patient is doing well 1 year after surgery. We
      report on the surgical management for pectus excavatum in adult patients. 

PMID- 24088910
TI  - Carney complex with biatrial cardiac myxoma.
AB  - Cardiac myxomas make up approximately 50% of all benign cardiac tumors and
      represented 86% of all surgically treated cardiac tumors. Most of them originated
      from the left atrium, in some cases from both of atria. We report a case of male
      patient with biatrial myxomas and other extra-cardiac involvement: hypophyseal
      adenoma, enlargement of thyroid gland, tubular adenoma polyp of colon and
      bilateral large cell calcifying Sertoli cell tumor (LCCSCT) of testis. These
      findings led to the diagnosis of Carney's complex, which is a syndrome with
      multiple neoplasias, cardiac myxomas, lentigines, and endocrine abnormalities. A
      genetic test confirm this diagnosis. 

PMID- 24088911
TI  - Cardiac papillary fibroelastoma: report of three cases.
AB  - Primary cardiac tumors are uncommon, and papillary fibroelastoma is considered
      relatively rare compared to myxoma and lipoma in the primary cardiac tumors. We
      experienced three cases of fibroelastoma. The patients' age was 28-75 years, and
      one patient was female. Two patients were presented with cerebral infarction and
      cardiac ischemia although, the other patient had no symptoms. Echocardiography
      revealed a hyperechoic mass in the left atrium, ventricle and on the aortic valve
      and helpful for differential diagnosis from myxoma. Surgical excision of the
      tumor was successfully performed in all patients and post-operative course was
      uncomplicated. 

PMID- 24088912
TI  - Invasiveness and malignant potential of pulmonary lesions presenting as pure
      ground-glass opacities.
AB  - PURPOSE: We retrospectively investigated the pathological diagnoses of pulmonary
      lesions presenting as pure ground-glass opacities (GGOs) to evaluate the risk of
      invasive malignancy. METHODS: We examined 191 GGO lesions, including 114 pure GGO
      and 77 mixed lesions, in 160 patients who underwent resection between January
      2008 and December 2010. RESULTS: Of the 114 pure GGO lesions, 14 (12%) were
      diagnosed as invasive lung cancer and 16 (14%) as minimally invasive
      adenocarcinoma. Twenty-one lesions exhibited pleural indentation on high
      resolution computed tomography (HRCT), and 5 of these were diagnosed as invasive
      cancer, indicating an invasive tendency of pure GGO lesions with pleural
      indentation (odds ratio, 2.64). Of 14 pure GGO lesions positive on positron
      emission tomography (PET), 8 were diagnosed as invasive lung cancer, indicating
      an invasive tendency of pure GGO lesions with PET positivity (odds ratio, 16.0; p
      <0.001; sensitivity, 67%; specificity, 89%). CONCLUSION: Invasive lung cancer
      accounted for 12% of the pure GGO lesions. Pure GGO lesions should be carefully
      monitored by periodic chest computed tomography, and surgical resection is
      recommended when they exhibit pleural indentation on HRCT or positivity on PET.

PMID- 24088913
TI  - Pleuroperitoneal shunt for refractory chylothorax accompanied with a mediastinal
      lymphangioma: a case report.
AB  - A 21-month-old Japanese boy was admitted with cough and hypoxemia. Chest X-ray
      showed massive right pleural effusion, which consisted of chyle. Computed
      tomography showed poor contrast area at superior and anterior mediastinum.
      Magnetic resonance imaging showed granular T2-low area at the same area.
      Lymphangioscintigraphy revealed a hot spot at superior mediastinum. These
      findings lead us to diagnose as mediastinal lymphangioma accompanied with
      chylothorax. Noninvasive treatments including total parenteral nutrition,
      administration of octreotide and sclerotherapy were tried, but all of them proved
      to be ineffective. Transfusions of blood products were frequently needed during
      these therapies. On the 48th hospital day, the mediastinal tumor and the thymus
      were excised through a median sternotomy. A leakage point of lymph into the
      intrathoracic space was not found, in spite of preoperative administration of
      milk with dye. Since the pleural effusion had continued to be drained,
      pleuroperitoneal shunt was placed on the 90th hospital day. The shunting amount
      continued to decline soon after the shunting, and had been under 10 ml/day since
      the 142nd day. The shunt was removed on the 148th day. There has been no
      reaccumulation of the pleural effusion and no recurrence of the mediastinal tumor
      for 1 year of observation. 

PMID- 24088914
TI  - Sclerosing rhabdomyosarcoma of a chest wall in an adult: a case report and review
      of the literature.
AB  - Sclerosing rhabdomyosarcoma (SRMS) is a newly recognized and rare variant of
      rhabdomyosarcoma. This soft tissue tumor has not yet been reported as a thoracic
      lesion. We report a case of a 26-year-old woman who presented with a large chest
      wall tumor. The tumor originated from the right anterior chest wall and protruded
      into the intra- and extrapleural cavity. A transcutaneous needle biopsy revealed
      spindle cells in an abundant hyalinized and fibrous stroma. Although the tumor
      was considered as a malignant soft-tissue neoplasm, a definitive diagnosis could
      not be established. A wide excision of the chest wall including the second, third
      and fourth rib and a part of sternum was performed. Histologically, cytoplasmic
      cross-striations were found in a portion of the tumor cells. The tumor cells were
      positive for muscle markers, and the tumor was diagnosed as rhabdomyosarcoma
      consistent with a sclerosing type of rhabdomyosarcoma. Eighteen months after the
      complete resection, the patient has pleural disseminations but is alive and
      undergoing chemotherapy. This case highlights the histologic features of a rare
      form of rhabdomyosarcoma, and emphasizes the importance of awareness of its
      existence and the utility of skeletal muscle markers in distinguishing sclerosing
      rhabdomyosarcoma from its mimics. 

PMID- 24088915
TI  - Effects of positive end-expiratory pressure on mechanical ventilation duration
      after coronary artery bypass grafting: a randomized clinical trial.
AB  - Patients undergoing cardiac surgery remain on mechanical ventilation
      postoperatively until they regain consciousness. Positive end-expiratory pressure
      (PEEP) may influence the duration of mechanical ventilation after coronary artery
      bypass grafting (CABG). The aim of this study was to compare the effects of
      different levels of PEEP on the duration of mechanical ventilation after coronary
      artery bypass grafting. This was a randomized clinical trial with 136 patients
      undergoing CABG between January 2011 and March 2012. We divided the patients into
      three groups with different levels of PEEP at the onset of mechanical
      ventilation: Group A, PEEP=5 cmH2O (n=44); Group B, PEEP=8 cmH2O (n=47) and Group
      C, PEEP=10 cmH2O (n=45). Mechanical ventilation time was obtained from a Physical
      Therapy Evaluation Form. We excluded patients with chronic obstructive pulmonary
      disease and those requiring concomitant, emergency or off-pump surgeries. For
      statistical analysis, we used the Kruskal-Wallis, G and Chi-square tests, with
      p<0.05 considered significant. From the point of weaning from mechanical
      ventilation until 12 hours after intensive care unit (ICU) admission, we saw a
      statistically different duration of mechanical ventilation between groups
      (p=0.029). In Group A, the average mechanical ventilation time was 6.7+/-3.2
      hours; it was 6.8+/-3.3 hours in Group B and 5.1+/-2.9 hours in Group C. The use
      of higher levels of PEEP was associated with shorter duration of mechanical
      ventilation in postoperative CABG patients.

PMID- 24088916
TI  - Malignant pleural mesothelioma presenting as acute empyema with severe
      leukocytosis.
AB  - Five months after the treatment for acute empyema, a 75-year-old woman was
      referred to our hospital because of marked elevation of the white blood cell
      (WBC) count and C-reactive protein (CRP) level, and a right pleural mass detected
      by chest computed tomography. At this time, the WBC count and CRP level had
      increased to 60400/microl and 18.2 mg/dl, respectively. We performed biopsy and
      the tumor was diagnosed as sarcomatoid malignant pleural mesothelioma. Malignant
      pleural mesothelioma occasionally presents the symptoms and findings like an
      acute empyema. We demonstrated the case of malignant pleural mesothelioma which
      had presented the symptoms and laboratory findings very similar to acute empyema
      and had treated as acute empyema. 

PMID- 24088917
TI  - Mitral valve repair in a patient with mesocardia.
AB  - A 75-year-old man was referred for treatment of mitral valve prolapse secondary
      to tendon rupture. He had been receiving oral and inhaled corticosteroids for
      bronchial asthma and bronchial ectasia. Chest X-ray showed cardiomegaly with
      protrusion of the right atrium shadow. Computed tomography revealed dislocation
      and counterclockwise rotation of the heart with the apex of the heart located in
      the mid-thorax, indicating mesocardia. We believed that it would have been
      difficult to expose the mitral valve through a right-sided left atrial approach.
      Thus, we planned to perform mitral valve repair via a trans-septal approach. The
      right thoracotomy approach was not suitable because of respiratory dysfunction.
      After a median sternotomy, the left anterior descending coronary artery was
      identified just beneath the midline of the sternum. Even after decompression of
      the heart under cardiopulmonary bypass, we could not obtain a good view of the
      right side of the left atrium. By a transseptal approach with a self-retaining
      retractor and atrial hooks, we obtained adequate exposure of the mitral valve and
      performed the mitral valve repair uneventfully. 

PMID- 24088918
TI  - Surgical resection of a solitary pulmonary metastasis from basaloid squamous cell
      carcinoma of the esophagus: a case report.
AB  - Basaloid squamous cell carcinoma (BSCC) of the esophagus is a relatively rare
      variant of esophageal malignancies. It is regarded as a disease with a poor
      prognosis because of the high frequency of distant metastases. We managed a case
      of resected solitary pulmonary metastasis of BSCC of the esophagus in a 78-year
      old female. We performed curative thoracic esophagectomy with three-field lymph
      node dissection for her disease. After two years and nine months, a thoracoscopic
      partial resection of the left lung was performed for the solitary pulmonary
      metastasis. At present, one year after the surgery, the patient is doing well
      without any recurrence. There have been few reports of case of resected pulmonary
      metastases. In addition, no treatment strategy for pulmonary metastases from BSCC
      of the esophagus has been established because of the limited number of cases.
      Additional cases are required to determine the treatment method. 

PMID- 24088919
TI  - Right native lung pneumonectomy due to over inflation three years after left
      single lung transplantation for pulmonary lymphangioleiomyomatosis.
AB  - Native lung hyperinflation (NLH) is one of the known complications after single
      lung transplantation (SLT). Generally, satisfactory results are achieved in
      patients undergoing SLT when simultaneous (or second stage) volume reduction of
      the contralateral native lung is performed. Contralateral native lung
      pneumonectomy after SLT is rarely reported. In this article, we report a case of
      a successful, right pneumonectomy of the native lung, 3 years after a left single
      lung transplant for pulmonary lymphangioleiomyomatosis (PLAM). The patient's
      pulmonary function and quality of life improved significantly after a right
      pneumonectomy of the native lung. 

PMID- 24088920
TI  - Giant solitary fibrous tumor of the pleura causing respiratory insufficiency:
      report of 3 cases.
AB  - We present 3 cases of solitary fibrous tumors (SFTs) occupying entire hemithorax
      and resulting in respiratory insufficiency. All patients were treated by complete
      resection, resulting in immediate re-expansion of the lungs and recovery from
      respiratory insufficiency. Although, two patients remain alive without
      recurrence, one patient had pleural recurrences three times over a 20-year
      period, all of which were treated by surgical resection. All of the primary
      tumors exhibited areas of hypercellularity, hemorrhage, or necrosis. All of the
      recurrent tumors in the recurrent case displayed large areas of hypercellularity,
      similar to the part of primary tumor. Although, the MIB-1 index in primary tumors
      was less than 5%, the index of the recurrent tumors increased up to 11% with
      repeated recurrence. Giant SFTs usually display hypercellularity, hemorrhage, or
      necrosis. Tumors with hypercellularity could recur. MIB-1 index could display
      malignant characteristics of recurrent tumors. Long-term follow-up for more than
      10 years after surgery is necessary, particularly for tumors with areas of
      hypercellularity. 

PMID- 24088921
TI  - Three-dimensional printing model of anomalous bronchi before surgery.
AB  - Lung surgeries in patients with bronchial variations have rarely been reported.
      Here, we describe the case of a patient along with lung cancer with variant
      anatomy of the right upper lobe bronchus. This variation was evaluated by three
      dimensional multi-detector computed tomography angiography with bronchography and
      a three-dimensional printing model using rapid prototyping. The variant anterior
      segment bronchus (S3) of the right upper lobe arising from the middle lobe
      bronchus was confirmed before surgery using the printing model, which helped to
      determine the extent of resection required and facilitated the understanding of
      the patient's anatomy during surgery. A thoracoscopic anterior segmentectomy and
      middle lobectomy were performed. The printing model was useful for detecting and
      evaluating the variant bronchi. 

PMID- 24088922
TI  - Adult mesenchymal hamartoma of the chest wall: report of a case.
AB  - We present an adult case of the chest wall tumor, which was accidentally pointed
      out by a medical checkup. Surgical resection was performed for the tumor, as
      preoperative biopsy of the tumor suggested the possibility of malignancy.
      Postoperative pathological examination revealed the diagnosis of mesenchymal
      hamartoma of the chest wall, which usually occurs in early infancy and childhood.
      Immunohistochemical staining for Sox9 was positive for chondrocytes and partially
      positive for spindle tumor cells. It is considered that the present case was not
      pointed out until the patient became an adult, because the tumor was relatively
      small and thus asymptomatic. 

PMID- 24088923
TI  - Surgical management of complete atrioventricular septal defect with tetralogy of
      fallot.
AB  - PURPOSE: The objective of this report is to evaluate our surgical approach to
      complete atrioventricular septal defect with tetralogy of Fallot (TOF) and to
      determine the best treatment for this malformation. METHODS: From 2007 to 2012,
      17 children underwent surgical correction of complete atrioventricular septal
      defect with TOF. Nine of these patients underwent complete correction, two
      underwent one and a half ventricle repair, and six underwent univentricular
      repair. RESULTS: There was 1 in-hospital death and 1 late death. Patients with
      lower weight required longer intensive care unit stay (P <0.05; r = -0.834).
      Follow-up data were available for all patients who survived the operation (range,
      3-60 months). The Kaplan-Meier curve indicated that 5-year survival was 88.2%.
      All survivors remained in good condition in New York Heart Association (NYHA)
      class I or II. CONCLUSION: Complete repair of atrioventricular septal defect with
      TOF has got favorable outcomes in terms of mortality and reoperation rate.
      Unbalanced atrioventricular septal defect with TOF can be managed well with one
      and a half ventricle repair. Two-patch technique through a transatrial approach
      alone is a good treatment choice for patients. Management of right ventricular
      outflow tract (RVOT) is similar to that of isolated TOF.

PMID- 24088924
TI  - Feasibility of using a vessel sealing system in a human pulmonary lobectomy: a
      retrospective comparison of this procedure with or without a vessel sealing
      system.
AB  - OBJECTIVE: Despite recent advances in video-assisted thoracoscopic lobectomy,
      some technical limitations still remain. Our current study purpose was to
      determine if the vessel sealing system (VSS) has utility in this procedure.
      METHOD: 112 patients who underwent an anatomic pulmonary lobectomy at our
      institute were evaluated retrospectively. The burst pressure of pulmonary
      vessels, which was divided into VSS (VSS group; n = 44) or manual ligature
      (ligature group; n = 53) groups, was measured experimentally in transected lungs.
      Perioperative clinical data was also retrospectively evaluated in patients
      treated with (VSS group) or without using VSS (n-VSS group). RESULTS: Burst
      pressures achieved adequate strength in both the VSS (600.0 +/- 436.8 mmHg) and
      ligature (1057.4 +/- 462.3 mmHg) groups. Compared with the n-VSS group, the VSS
      group patients showed lower intraoperative blood loss (115.4 +/- 181.1 vs. 183.3
      +/- 159.1 ml), lower chest fluids by 3rd post-operative day (POD) (533.8 +/-
      264.8 vs. 705.3 +/- 339.3 ml) and a shorter period of chest tube duration (4.1 +/
      1.2 vs. 5.4 +/- 2.4 days). No serious complications or perioperative (30 days)
      deaths occurred in either group. CONCLUSION: The VSS device has the advantage in
      pulmonary lobectomy procedures, especially those involving video-assisted
      thoracic surgery (VATS).

PMID- 24088925
TI  - Adverse events of stapling in thoracic surgery: relations between an incidence of
      adverse events and a stapling volume.
AB  - PURPOSE: The use of staplers for thoracic surgery has been widely accepted and
      regarded as a safe procedure. However, sometimes adverse events (AEs) of stapling
      are experienced. The aim of the present study was to retrospectively analyze AEs
      of stapling in thoracic surgery. METHODS: A retrospective multi-institutional
      review was conducted by the 27 institutions of the Central Japan Lung Cancer
      Surgery Study Group. Between January 2009 and December 2010, 4495 patients
      underwent thoracic surgery using mechanical stapling. RESULTS: Stapling of
      various tissues was performed 16403 times. Total number of AEs related to
      stapling was 126 (0.77%). One hundred and nine events occurred intraoperative and
      17 events occurred postoperative. The AE rates ranged from 0% to 1.8%. No
      relationship was seen between the incidence of AE and a stapling volume of
      thoracic surgery. CONCLUSION: We have investigated intraoperative and
      postoperative AEs of stapling. Generally, stapling in thoracic surgery was safe.
      An AE rate of stapling in thoracic surgery is not influenced by the numbers of
      stapling in institutions.

PMID- 24088926
TI  - Endobronchial closure of a bronchopleural fistula using a fibrin glue-coated
      collagen patch and fibrin glue.
AB  - Bronchopleural fistulas associated with empyema can occur as life-threatening
      sequelae after pulmonary resection, occurring most frequently after
      pneumonectomy. Three bronchopleural fistulas, 5-6 mm in diameter, were
      successfully treated using a fibrin glue-coated collagen patch (FGCCP) and fibrin
      glue (FG) at the site of a bronchopleural fistula. Through the clinical
      experiences, we introduce the methodology to perform the endobronchial closure of
      bronchopleural fistulas.Data were collected by reviewing the clinical charts of
      patients diagnosed with post-lobectomy bronchopleural fistula at Sapporo Minami
      Sanjo Hospital from June 2004 to December 2010. Bronchopleural fistula was
      diagnosed by means of endoscopic visualization. Three cases of post-lobectomy and
      one case of post-pneumonectomy bronchopleural fistula were collected.A FGCCP
      fragment was packed within the fistula, and the fragment grasped with the forceps
      was kept in this position for approximately a minute, a time during which a FGCCP
      becomes adhesive, and the patch fragment was released. After releasing the patch
      fragment, the FG was applied directly on the FGCCP using a two-channel
      catheter.There have been few reports of the bronchoscopic closure of
      bronchopleural fistulas using a FGCCP and FG. Closure of small bronchopleural
      fistulas with the application of a FGCCP and FG may offer a valuable therapeutic
      alternative. 

PMID- 24088927
TI  - Attenuation of lung ischemia-reperfusion injury by rho-associated kinase
      inhibition in a rat model of lung transplantation.
AB  - BACKGROUND: A signaling pathway of the small GTPase Rho and Rho-associated coiled
      coil-forming protein kinase (ROCK), regulates the contraction of endothelial
      cells. We studied the effects of Y-27632, a specific ROCK inhibitor, to clarify
      the role of Rho/ROCK in the pathogenesis of ischemia-reperfusion lung injury in a
      rat model of single-lung transplantation (LTX). METHODS: We flushed 5 donor rat
      lungs with Euro-Collins solution, and 5 donor lungs with Euro-Collins + Y-27632,
      0.03 mg/ml, and preserved the lungs for 6 h at 4 degrees C before reperfusion for
      4 h. The 5 rat recipients of Y-27632-treated lungs also received a 10-mg/kg bolus
      of Y-27632 i.p. 30 min before reperfusion. RESULTS: Pretreatment of the donor
      lungs and recipient rats with Y-27632 prominently suppressed the post-LTX edema,
      while the permeability index was only slightly decreased. The (1) numbers of
      neutrophils and macrophages, and (2) tumor necrosis factor (TNF)-alpha
      concentration, were significantly lower in the bronchoalveolar lavage fluid of
      treated than untreated lungs. CONCLUSIONS: Y-27632 (1) inhibited the migration of
      inflammatory cells into the alveolar space, (2) decreased the production of TNF
      alpha, and (3) attenuated the edema after LTX. Endothelial Rho and ROCK may play
      an important role in the pathogenesis of post-LTX injury.

PMID- 24088928
TI  - Management of corneal lacerations and perforations.

PMID- 24088929
TI  - Traumatic in-the-bag intraocular lens subluxation.

PMID- 24088930
TI  - Corneal trauma following keratoplasty.

PMID- 24088931
TI  - Role of amniotic membrane transplantation in acute chemical injury.

PMID- 24088932
TI  - The pediatric traumatic hyphema.

PMID- 24088933
TI  - A review of traumatic macular hole: diagnosis and treatment.

PMID- 24088934
TI  - Choroidal rupture: a review.

PMID- 24088935
TI  - Retinal detachment after open-globe injury.

PMID- 24088936
TI  - Traumatic endophthalmitis, retinal detachment, and metallosis after intraocular
      foreign body injuries.

PMID- 24088937
TI  - Neuroprotection for retinal detachment.

PMID- 24088938
TI  - Traumatic chorioretinal rupture (sclopetaria).

PMID- 24088939
TI  - Surgical techniques in the management of perforating injuries of the globe.

PMID- 24088940
TI  - Endoscopic pars plana vitrectomy for the management of severe ocular trauma.

PMID- 24088941
TI  - Naso-orbito-ethmoidal (NOE) fractures: a review.

PMID- 24088942
TI  - Intraorbital foreign bodies: retrospective chart review and review of literature.

PMID- 24088943
TI  - Prophylactic antibiotics in posttraumatic infectious endophthalmitis.

PMID- 24088944
TI  - Ocular siderosis.

PMID- 24088945
TI  - Corneal alkali burns: a review of the literature and proposed protocol for
      evaluation and treatment.

PMID- 24088947
TI  - Subspecialties of ophthalmic practice.

PMID- 24088948
TI  - Photosystem II antenna phosphorylation-dependent protein diffusion determined by
      fluorescence correlation spectroscopy.
AB  - Flexibility of chloroplast thylakoid membrane proteins is essential for plant
      fitness and survival under fluctuating light environments. Phosphorylation of
      light-harvesting antenna complex II (LHCII) is known to induce dynamic protein
      reorganization that fine-tunes the rate of energy conversion in each photosystem.
      However, molecular details of how LHCII phosphorylation causes light energy
      redistribution throughout thylakoid membranes still remain unclear. By using
      fluorescence correlation spectroscopy, we here determined the LHCII
      phosphorylation-dependent protein diffusion in thylakoid membranes isolated from
      the green alga Chlamydomonas reinhardtii. As compared to the LHCII
      dephosphorylation-induced condition, the diffusion coefficient of LHCII increased
      nearly twofold under the LHCII phosphorylation-induced condition. We also
      verified the results by using the LHCII phosphorylation-deficient mutant. Our
      observation suggests that LHCII phosphorylation-dependent protein reorganization
      occurs along with the changes in the rate of protein diffusion, which would have
      an important role in mediating light energy redistribution throughout thylakoid
      membranes. 

PMID- 24088949
TI  - Modeling Alzheimer's Disease Progression Using Disease Onset Time and Disease
      Trajectory Concepts Applied to CDR-SOB Scores From ADNI.
AB  - Disease-onset time (DOT) and disease trajectory concepts were applied to derive
      an Alzheimer's disease (AD) progression population model using the clinical
      dementia rating scale-sum of boxes (CDR-SOB) from the AD neuroimaging initiative
      (ADNI) database. The model enabled the estimation of a DOT and a disease
      trajectory for each patient. The model also allowed distinguishing fast and slow
      progressing subpopulations according to the functional assessment questionnaire,
      normalized hippocampal volume, and CDR-SOB score at study entry. On the basis of
      these prognostic factors, 81% of the mild cognitive impairment (MCI) subjects
      could correctly be assigned to slow or fast progressers, and 77% of MCI to AD
      conversions could be predicted whereas the model described correctly 84% of the
      conversions. Finally, synchronization of the biomarker-time profiles on estimated
      individual DOT virtually expanded the population observation period from 3 to 8
      years. DOT-disease trajectory model is a powerful approach that could be applied
      to many progressive diseases.CPT: Pharmacometrics & Systems Pharmacology (2013)
      2, e78; doi:10.1038/psp.2013.54; advance online publication 2 October 2013. 

PMID- 24088950
TI  - Boosting that tan with a bit of voltage.

PMID- 24088951
TI  - Exploiting shape effects of La2O3 nanocatalysts for oxidative coupling of methane
      reaction.
AB  - High activity towards oxidative coupling of methane and high selectivity for C2
      hydrocarbons could be achieved over La2O3 nanorods with a large surface area,
      strong surface basic sites, electron deficient surface oxygen species and defined
      surface structure compared with La2O3 nanoparticles at low temperature. 

PMID- 24088953
TI  - The Nrf2 triterpenoid activator, CDDO-imidazolide, protects kidneys from ischemia
      reperfusion injury in mice.
AB  - Acute kidney injury (AKI) caused by ischemia-reperfusion is a major clinical
      problem in both native and transplanted kidneys. We had previously shown that
      deficiency of Nrf2, a potent bZIP transcription factor that binds to the
      antioxidant response element, enhances susceptibility to experimental ischemic
      AKI. Here we further explored the role of Nrf2 in AKI by amplifying Nrf2
      activation in vivo and in vitro with the synthetic triterpenoid CDDO-imidazolide.
      Mice treated with CDDO-imidazolide and undergoing experimental bilateral ischemic
      AKI had improved survival and renal function. Treated mice had improved renal
      histology with a decrease in tubular injury, as well as a decrease in
      proinflammatory cytokine and chemokine production compared with vehicle-treated
      mice. In an exploration of protective mechanisms, we found an upregulation of
      Nrf2 target antioxidant genes in CDDO-imidazolide-treated mouse kidneys.
      Furthermore, Nrf2-deficient mice treated with CDDO-imidazolide had no significant
      improvement in mortality, renal function or histology, proinflammatory cytokine
      gene expression, and no significant increase in antioxidant gene expression. In
      vitro studies demonstrated that the renal epithelial cells were likely an
      important target of CDDO-imidazolide. Thus, activation of Nrf2 signaling with
      CDDO-imidazolide confers protection from AKI, and presents a new therapeutic
      opportunity for this common and serious condition. 

PMID- 24088952
TI  - Kidney xenotransplantation.
AB  - Xenotransplantation using pigs as donors offers the possibility of eliminating
      the chronic shortage of donor kidneys, but there are several obstacles to be
      overcome before this goal can be achieved. Preclinical studies have shown that,
      while porcine renal xenografts are broadly compatible physiologically, they
      provoke a complex rejection process involving preformed and elicited antibodies,
      heightened innate immune cell reactivity, dysregulated coagulation, and a strong
      T cell-mediated adaptive response. Furthermore, the susceptibility of the
      xenograft to proinflammatory and procoagulant stimuli is probably increased by
      cross-species molecular defects in regulatory pathways. To balance these
      disadvantages, xenotransplantation has at its disposal a unique tool to address
      particular rejection mechanisms and incompatibilities: genetic modification of
      the donor. This review focuses on the pathophysiology of porcine renal xenograft
      rejection, and on the significant genetic, pharmacological, and technical
      progress that has been made to prolong xenograft survival. 

PMID- 24088954
TI  - Losartan reverses permissive epigenetic changes in renal glomeruli of diabetic
      db/db mice.
AB  - Epigenetic mechanisms such as chromatin histone H3 lysine methylation and
      acetylation have been implicated in diabetic vascular complications. However,
      histone modification profiles at pathologic genes associated with diabetic
      nephropathy in vivo and their regulation by the angiotensin II type 1 receptor
      (AT1R) are not clear. Here we tested whether treatment of type 2 diabetic db/db
      mice with the AT1R blocker losartan not only ameliorates diabetic nephropathy,
      but also reverses epigenetic changes. As expected, the db/db mice had increased
      blood pressure, mesangial hypertrophy, proteinuria, and glomerular expression of
      RAGE and PAI-1 vs. control db/+ mice. This was associated with increased RNA
      polymerase II recruitment and permissive histone marks as well as decreased
      repressive histone marks at these genes, and altered expression of relevant
      histone modification enzymes. Increased MCP-1 mRNA levels were not associated
      with such epigenetic changes, suggesting post-transcriptional regulation.
      Losartan attenuated key parameters of diabetic nephropathy and gene expression,
      and reversed some but not all the epigenetic changes in db/db mice. Losartan also
      attenuated increased H3K9/14Ac at RAGE, PAI-1, and MCP-1 promoters in mesangial
      cells cultured under diabetic conditions. Our results provide novel information
      about the chromatin state at key pathologic genes in vivo in diabetic nephropathy
      mediated in part by AT1R. Thus, combination therapies targeting epigenetic
      regulators and AT1R could be evaluated for more effective treatment of diabetic
      nephropathy. 

PMID- 24088955
TI  - Establishing a clinical trials network in nephrology: experience of the
      Australasian Kidney Trials Network.
AB  - Chronic kidney disease is a major public health problem globally. Despite this,
      there are fewer high-quality, high-impact clinical trials in nephrology than
      other internal medicine specialties, which has led to large gaps in evidence. To
      address this deficiency, the Australasian Kidney Trials Network, a Collaborative
      Research Group, was formed in 2005. Since then, the Network has provided
      infrastructure and expertise to conduct patient-focused high-quality,
      investigator-initiated clinical trials in nephrology. The Network has not only
      been successful in engaging the nephrology community in Australia and New Zealand
      but also in forming collaborations with leading researchers from other countries.
      This article describes the establishment, development, and functions of the
      Network. The article also discusses the current and future funding strategies to
      ensure uninterrupted conduct of much needed clinical trials in nephrology to
      improve the outcomes of patients affected by kidney diseases with cost-effective
      interventions. 

PMID- 24088956
TI  - The prevalence, severity, and association with HbA1c and fibrinogen of cognitive
      impairment in chronic kidney disease.
AB  - Cognitive impairment is a frequent finding in patients with chronic kidney
      disease (CKD). We examined cognitive performance in a prospective study of 119
      patients with CKD stages 3-5 (including dialysis) and 54 control patients of the
      same age without CKD but with similar vascular risk profiles. Analysis included a
      comprehensive test battery evaluating memory, information processing speed,
      executive function, language, and visuoconstructive function, in addition to
      depression and anxiety. Thirty percent of patients with CKD had cognitive
      deficits (one or more s.d. below control patient performance). Cognitive deficits
      (T-value related to published norm values) were mild but significantly decreased
      to 48.8 in patients with stage 3-5 CKD not requiring hemodialysis and 47.2 in
      patients with stage 5D disease requiring hemodialysis, compared with 51.5 in
      control patients. Linear regressions among patients with CKD (forced entry
      strategy) showed that age (beta=-0.50 per s.d.), HbA1c (beta=-0.18 per s.d.), and
      fibrinogen (beta=-0.18 per s.d.) predicted cognitive performance. Interestingly,
      HbA1c discriminated cognition in all age groups, while fibrinogen differentiated
      cognition particularly in patients over 70 years of age. Thus, our cross
      sectional study suggests the severity of cognitive impairment in CKD is mild. As
      such, longitudinal studies are required to further characterize the role of
      cognitive deficits in CKD. 

PMID- 24088958
TI  - Histologic classification of glomerular diseases: clinicopathologic correlations,
      limitations exposed by validation studies, and suggestions for modification.
AB  - The value of classification systems applied to the examination of renal biopsies
      is based on several factors: first, on the ability to provide efficient
      communication between pathologists and between pathologists and clinicians;
      second, on the possibility to implement diagnostic information with prognostic
      indication. Even more important, the practical value of a classification is
      proved by the ability of providing elements that guide therapeutic decisions and
      can be used in the follow-up of the patient. With these aims, new histologic
      classification systems have been proposed in the last decade for lupus nephritis
      and IgA nephropathy under the leadership of the Renal Pathology Society and the
      International Society of Nephrology. These classifications have gained a
      significant level of worldwide acceptance and have been the subject of multiple
      single-center and multicenter validation studies, which have underpinned their
      clinical benefits and limitations and served to highlight remaining questions and
      difficulties of interpretation of the biopsy sample. More recently, a
      classification system has also been proposed for ANCA-associated crescentic
      glomerulonephritis (ANCA-GN), although the validation process for this is still
      in an early stage. In this review, we examine in some detail the ISN/RPS
      classification for lupus nephritis and the Oxford classification for IgA
      nephropathy, with emphasis on clinicopathologic correlations, their value for and
      evolving impact on clinical studies and clinical practice, and their significant
      limitations in this regard as exposed by validation studies. We also suggest
      possible ways by which these classifications might be modified to make them more
      applicable to clinical practice. Finally, we more briefly discuss the newly
      proposed classification for ANCA-GN. 

PMID- 24088957
TI  - Prompt plasma exchanges and immunosuppressive treatment improves the outcomes of
      anti-factor H autoantibody-associated hemolytic uremic syndrome in children.
AB  - Antibodies to complement factor H are an uncommon cause of hemolytic uremic
      syndrome (HUS). Information on clinical features and outcomes in children is
      limited. In order to explore this we studied a multicenter cohort of 138 Indian
      children with anti-complement factor H antibody associated HUS, constituting 56%
      of patients with HUS. Antibody titers were high (mean 7054 AU/ml) and correlated
      inversely with levels of complement C3, but not complement factor H. Homozygous
      deletion of the CFHR1 gene was found in 60 of 68 patients. Therapies included
      dialysis in 119 children, 105 receiving plasma exchanges and 26 intravenous
      immunoglobulin. Induction immunosuppression consisted of 87 children receiving
      prednisolone with or without intravenous cyclophosphamide or rituximab. Antibody
      titers fell significantly following plasma exchanges and increased during
      relapses. Adverse outcome (stage 4-5 CKD or death) was seen in 36 at 3 months and
      41 by last follow up, with relapse in 14 of 122 available children. Significant
      independent risk factors for adverse outcome were an antibody titer over 8000
      AU/ml, low C3 and delay in plasma exchange. Combined plasma exchanges and
      induction immunosuppression resulted in significantly improved renal survival:
      one adverse outcome prevented for every 2.6 patients treated. Maintenance
      immunosuppressive therapy, of prednisolone with either mycophenolate mofetil or
      azathioprine, significantly reduced the risk of relapses. Thus, prompt use of
      immunosuppressive agents and plasma exchanges are useful for improving outcomes
      in pediatric patients with anti-complement factor H-associated HUS. 

PMID- 24088959
TI  - Lineage-tracing methods and the kidney.
AB  - The kidney is a complex organ with over 30 different cell types, and
      understanding the lineage relationships between these cells is challenging.
      During nephrogenesis, a central question is how the coordinated morphogenesis,
      growth, and differentiation of distinct cell types leads to development of a
      functional organ. In mature kidney, understanding cell division and fate during
      injury, regeneration and aging are critical topics for understanding disease.
      Genetic lineage tracing offers a powerful tool to decipher cellular hierarchies
      in both development and disease because it allows the progeny of a single cell,
      or group of cells, to be tracked unambiguously. Recent advances in this field
      include the use of inducible recombinases, multicolor reporters, and mosaic
      analysis. In this review, we discuss lineage-tracing methods focusing on the
      mouse model system and consider the impact of these methods on our understanding
      of kidney biology and prospects for future application. 

PMID- 24088961
TI  - A systematic review and meta-analysis of the influence of peritoneal dialysis
      catheter type on complication rate and catheter survival.
AB  - Peritoneal dialysis (PD) is an effective treatment for end-stage renal disease.
      There are several configurations of PD catheter design that may impact catheter
      function, such as the shape of the intraperitoneal segment, the number of cuffs,
      and the subcutaneous configuration. This review and meta-analysis was carried out
      to determine whether there is a clinical advantage for one of the catheter types
      or configurations. Comprehensive searches were conducted in MEDLINE, Embase, and
      CENTRAL (the Cochrane Library 2012, issue 10). The methodology was in accordance
      with the Cochrane Handbook for Interventional Systematic Reviews and written
      based on the PRISMA statement. The initial search yielded 682 hits from which 13
      randomized controlled trials were identified. Outcomes of interest were as
      follows: catheter survival, drainage dysfunction, migration, leakage, exit-site
      infections, peritonitis, and catheter removal. Comparing straight vs. swan neck
      and single vs. double-cuffed catheters, no differences were found when results
      were pooled. Comparison of straight vs. coiled-tip catheters demonstrated that
      survival was significantly different in favor of straight catheters (hazard ratio
      2.05; confidence interval 1.10-3.79, P=0.02). For surgically inserted catheters,
      the removal rate and survival at 1 year after insertion were significantly in
      favor of straight catheters. Our meta-analysis clearly demonstrates benefits for
      catheters with a straight intraperitoneal segment. 

PMID- 24088960
TI  - Fibroblast growth factor 23 accelerates phosphate-induced vascular calcification
      in the absence of Klotho deficiency.
AB  - Fibroblast growth factor 23 (FGF23) is a phosphate-regulating hormone that acts
      primarily on the kidney and parathyroid. With declining kidney function there is
      an increase in circulating FGF23 levels, which is associated with vascular
      calcification and mortality in chronic kidney disease. Whether FGF23 exerts
      direct effects on vasculature is unclear. We evaluated the expression of Klotho
      and FGF receptors in rat aortic rings and rat aorta vascular smooth muscle cells
      maintained in culture by reverse transcription-PCR, western blotting, and
      immunostaining. Signaling pathways underlying FGF23 effects were assessed by
      western blotting, and effects of FGF23 on osteogenic markers and phosphate
      transporters were assessed by real-time reverse transcription-PCR. We detected
      Klotho and FGFR1 in total aorta but not in vascular smooth muscle cells. FGF23
      augmented phosphate-induced vascular calcification in the aortic rings from
      uremic rats and dose dependently increased ERK1/2 phosphorylation in Klotho
      overexpressing but not naive vascular smooth muscle cells. FGF23-induced ERK1/2
      phosphorylation was inhibited by SU5402 (FGFR1 inhibitor) and U0126 (MEK
      inhibitor). FGF23 enhanced phosphate-induced calcification in Klotho
      overexpressing vascular smooth muscle cells and increased osteoblastic marker
      expression, which was inhibited by U0126. In contrast, phosphate transporter
      expression was not affected by phosphate or FGF23. Thus, FGF23 enhances phosphate
      induced vascular calcification by promoting osteoblastic differentiation
      involving the ERK1/2 pathway. 

PMID- 24088962
TI  - Transforming growth factor-beta1-mediated renal fibrosis is dependent on the
      regulation of transforming growth factor receptor 1 expression by let-7b.
AB  - Renal fibrosis results from excessive accumulation of extracellular matrix mainly
      driven by transforming growth factor-beta1 (TGF-beta1). Certain microRNAs have
      been implicated in this disease, and here we examine the role of let-7b. Rat
      proximal tubular epithelial cells (NRK52E) were treated with TGF-beta1 for 3 days
      to assess the expression of markers of fibrosis and let-7b. These factors were
      also assessed in two mouse models representing early and more advanced diabetic
      nephropathy and in the non-diabetic adenine-induced renal fibrosis model. TGF
      beta1 downregulated the expression of let-7b and induced fibrogenesis in NRK52E
      cells. Ectopic expression of let-7b repressed TGF-beta1 receptor 1 (TGFBR1)
      expression directly by targeting the two let-7b binding sites in the 3'
      untranslated region of that gene, reduced expression of extracellular matrix
      proteins, decreased SMAD3 activity, and attenuated the profibrotic effects of TGF
      beta1. Knockdown of let-7b elevated TGFBR1 expression and mimicked some of the
      profibrotic effects of TGF-beta1. Consistent with these observations, let-7b
      expression was also reduced in models of both diabetic and non-diabetic renal
      fibrosis with the upregulation of TGFBR1. Thus, let-7b microRNA represents a
      potential new target for the treatment of renal fibrosis in diabetic and non
      diabetic nephropathy. 

PMID- 24088963
TI  - Synthesis and evaluation of cyanine-styryl dyes with enhanced photostability for
      fluorescent DNA staining.
AB  - The photostability of cyanine-styryl dyes of the indole-quinolinium type can be
      significantly improved by structural variations while the excellent optical
      properties including the bright fluorescence in the presence of DNA can be
      maintained or even improved, too. 

PMID- 24088964
TI  - Impact of nonoperative treatment, vertebroplasty, and kyphoplasty on survival and
      morbidity after vertebral compression fracture in the medicare population.
AB  - BACKGROUND: The treatment of vertebral compression fractures with vertebral
      augmentation procedures is associated with acute pain relief and improved
      mobility, but direct comparisons of treatments are limited. Our goal was to
      compare the survival rates, complications, lengths of hospital stay, hospital
      charges, discharge locations, readmissions, and repeat procedures for Medicare
      patients with new vertebral compression fractures that had been acutely treated
      with vertebroplasty, kyphoplasty, or nonoperative modalities. METHODS: The 2006
      Medicare Provider Analysis and Review File database was used to identify 72,693
      patients with a vertebral compression fracture. Patients with a previous
      vertebral compression fracture, those who had had a vertebral augmentation
      procedure in the previous year, those with a diagnosis of malignant neoplasm, and
      those who had died were excluded, leaving 68,752 patients. The patients were
      stratified into nonoperative treatment (55.6%), vertebroplasty (11.2%), and
      kyphoplasty (33.2%) cohorts. Survival rates were compared with use of Kaplan
      Meier analysis and Cox regression. Results were adjusted for potential
      confounding variables. Secondary parameters of interest were analyzed with the
      chi-square test (categorical variables) and one-way analysis of variance
      (continuous variables), with the level of significance set at p < 0.05. RESULTS:
      The estimated three-year survival rates were 42.3%, 49.7%, and 59.9% for the
      nonoperative treatment, vertebroplasty, and kyphoplasty groups, respectively. The
      adjusted risk of death was 20.0% lower for the kyphoplasty group than for the
      vertebroplasty group (hazard ratio = 0.80, 95% confidence interval, 0.77 to
      0.84). Patients in the kyphoplasty group had the shortest hospital stay and the
      highest hospital charges and were the least likely to have had pneumonia and
      decubitus ulcers during the index hospitalization and at six months
      postoperatively. However, kyphoplasty was more likely to result in a subsequent
      augmentation procedure than was vertebroplasty (9.41% compared with 7.89%; p <
      0.001). CONCLUSIONS: Vertebral augmentation procedures appear to be associated
      with longer patient survival than nonoperative treatment does. Kyphoplasty tends
      to have a more striking association with survival than vertebroplasty does, but
      it is costly and may have a higher rate of subsequent vertebral compression
      fracture. These provocative findings may reflect selection bias and should be
      addressed in a prospective, direct comparison of methods to treat vertebral
      compression fractures. LEVEL OF EVIDENCE: Therapeutic Level III. See Instructions
      for Authors for a complete description of levels of evidence.

PMID- 24088965
TI  - Surgical treatment of distal radial fractures with a volar locking plate versus
      conventional percutaneous methods: a randomized controlled trial.
AB  - BACKGROUND: The aim of this study was to compare the outcomes of displaced distal
      radial fractures treated with a volar locking plate with the results of such
      fractures treated with a conventional method of closed reduction and percutaneous
      wire fixation with supplemental bridging external fixation when required. Our aim
      was to ascertain whether the use of a volar locking plate improves functional
      outcomes. METHODS: A single-center, pragmatic, randomized controlled trial was
      conducted in a tertiary care institution. One hundred and thirty patients
      (eighteen to seventy-three years of age) who had a displaced distal radial
      fracture were randomized to treatment with either a volar locking plate (n = 66)
      or a conventional percutaneous fixation method (n = 64). Outcome assessments were
      conducted at six weeks, twelve weeks, and one year. Outcomes were measured on the
      basis of scores on the Patient Evaluation Measure (PEM) and QuickDASH
      questionnaire (a shortened version of the Disabilities of the Arm, Shoulder and
      Hand, or DASH, Outcome Measure), EuroQol-5D (EQ-5D) scores, wrist range of
      motion, grip strength, and radiographic parameters. RESULTS: The rate of follow
      up at one year was 95%. Patients in the volar locking-plate group had
      significantly better PEM and QuickDASH scores and range of motion at six weeks
      compared with patients in the conventional-treatment group, but there were no
      significant differences between the two groups at twelve weeks or one year. Grip
      strength was better in the plate group at all time points. The volar locking
      plate was better at restoring palmar tilt and radial height. Significantly more
      patients in the plate group were driving at the end of six weeks, but this did
      not translate to a significant difference between groups in terms of those
      returning to work by that time. CONCLUSIONS: Use of a volar locking plate
      resulted in a faster early recovery of function compared with use of conventional
      methods. However, no functional advantage was demonstrated at or beyond twelve
      weeks. Use of the volar locking plate resulted in better anatomical reduction and
      grip strength, but there was no significant difference in function between the
      groups at twelve weeks or one year. The earlier recovery of function may be of
      advantage to some patients. LEVEL OF EVIDENCE: Therapeutic Level I. See
      Instructions for Authors for a complete description of levels of evidence.

PMID- 24088966
TI  - Growing-rod graduates: lessons learned from ninety-nine patients who completed
      lengthening.
AB  - BACKGROUND: Growing-rod spinal instrumentation systems are a valuable tool for
      managing severe early-onset scoliosis. There is little information about the end
      point of treatment. METHODS: A multicenter early-onset-scoliosis database was
      searched to identify patients who had undergone treatment with growing rods and
      either had had a final operative procedure or were still being treated with the
      growing rods after reaching skeletal maturity (defined as fourteen years of age
      or older). Clinical, radiographic, and operative data were analyzed. RESULTS:
      Ninety-nine patients met the inclusion criteria, and ninety-two (93%) of them had
      had a final operative procedure. The remaining seven patients (7%) were older
      than fourteen years but had not undergone a final procedure. Of the ninety-two
      patients who had a final procedure, seventy-nine (86%) had an instrumented
      fusion, nine (10%) had growing-rod exchanges and fusion in situ, three (3%) had
      the growing rods left in place and fusion in situ, and one (1%) had only growing
      rod removal. The mean age (and standard deviation) at the final fusion was 12.4
      +/- 1.9 years. In forty-four (55%) of eighty patients for whom the information
      was available, the number of vertebral levels fused was the same as the number of
      vertebral levels spanned by the growing rods. The percent correction of the curve
      after final fusion was none or minimal (<= 20 %) in eleven (18%) of the sixty-two
      patients for whom sufficient-quality radiographs were available, moderate (21% to
      50%) in thirty (48%), and substantial (>= 51 %) in nine (15%); the curve had
      worsened in twelve patients (19%). The mean duration of growing-rod treatment was
      5.0 +/- 2.6 years. Of fifty-eight operative reports made at final fusion that
      contained comments on spinal flexibility, eleven (19%) described the spine as
      being mobile, eleven (19%) described decreased flexibility, and thirty-six (62%)
      described the spine as being completely stiff. At final fusion, twenty-two
      patients (24%) had osteotomies and seven patients (8%) had a thoracoplasty.
      CONCLUSIONS: Most patients underwent growing-rod removal and final instrumented
      fusion. The final fusion often included the same levels spanned by the growing
      rods and usually achieved <50% additional correction of the deformity remaining
      at the end of the growing-rod management. LEVEL OF EVIDENCE: Therapeutic Level
      IV. See Instructions for Authors for a complete description of levels of
      evidence.

PMID- 24088967
TI  - Societal and economic impact of anterior cruciate ligament tears.
AB  - BACKGROUND: An anterior cruciate ligament (ACL) tear is a common knee injury,
      particularly among young and active individuals. Little is known, however, about
      the societal impacts of ACL tears, which could be large given the typical patient
      age and increased lifetime risk of knee osteoarthritis. This study evaluates the
      cost-effectiveness of ACL reconstruction compared with structured rehabilitation
      only. METHODS: A cost-utility analysis of ACL reconstruction compared with
      structured rehabilitation only was conducted with use of a Markov decision model
      over two time horizons: the short to intermediate term (six years), on the basis
      of Level-I evidence derived from the KANON Study and the Multicenter Orthopaedic
      Outcomes Network (MOON) database; and the lifetime, on the basis of a
      comprehensive literature review. Utilities were assessed with use of the SF-6D.
      Costs (in 2012 U.S. dollars) were estimated from the societal perspective and
      included the effects of the ACL tear on work status, earnings, and disability.
      Effectiveness was expressed as quality-adjusted life years (QALYs) gained.
      RESULTS: In the short to intermediate term, ACL reconstruction was both less
      costly (a cost reduction of $4503) and more effective (a QALY gain of 0.18)
      compared with rehabilitation. In the long term, the mean lifetime cost to society
      for a typical patient undergoing ACL reconstruction was $38,121 compared with
      $88,538 for rehabilitation. ACL reconstruction resulted in a mean incremental
      cost savings of $50,417 while providing an incremental QALY gain of 0.72 compared
      with rehabilitation. Effectiveness gains were driven by the higher probability of
      an unstable knee and associated lower utility in the rehabilitation group.
      Results were most sensitive to the rate of knee instability after initial
      rehabilitation. CONCLUSIONS: ACL reconstruction is the preferred cost-effective
      treatment strategy for ACL tears and yields reduced societal costs relative to
      rehabilitation once indirect cost factors, such as work status and earnings, are
      considered. The cost of an ACL tear over the lifetime of a patient is
      substantial, and resources should be directed to developing innovations for
      injury prevention and for altering the natural history of an ACL injury.

PMID- 24088968
TI  - Accuracy of acetabular component position in hip arthroplasty.
AB  - BACKGROUND: Acetabular component malposition is linked to higher bearing surface
      wear and component instability. Outcomes following total hip arthroplasty and
      surface replacement arthroplasty depend on multiple surgeon and patient-dependent
      factors. The purpose of this study was to examine the frequency in which
      acetabular components are placed within a predetermined target range. METHODS: We
      evaluated postoperative anteroposterior pelvic radiographs for every consecutive
      primary total hip arthroplasty and surface replacement arthroplasty completed
      from 2004 to 2009 at a single institution. Acetabular component abduction and
      anteversion angles were determined using Martell Hip Analysis Suite software. We
      defined target ranges for abduction and anteversion for both total hip
      arthroplasty (30 degrees  to 55 degrees  and 5 degrees  to 35 degrees ,
      respectively) and surface replacement arthroplasty (30 degrees  to 50 degrees 
      and 5 degrees  to 25 degrees , respectively). Surgeon and patient-related factors
      were analyzed for risk associated with placing the acetabular component outside
      the target range. RESULTS: Of the 1549 total hip arthroplasties, 1435 components
      (93%) met our abduction target, 1472 (95%) met our anteversion target, and 1363
      (88%) simultaneously met both targets. Of the 263 surface replacement
      arthroplasties, 233 components (89%) met our abduction target, 247 (94%) met our
      anteversion target, and 220 (84%) simultaneously met both targets. When
      previously published target ranges of abduction (30 degrees  to 45 degrees ) and
      anteversion (5 degrees  to 25 degrees ) angles were used, only 665 total hip
      replacements (43%) met the abduction target, 1325 (86%) met the anteversion
      target, and 584 (38%) simultaneously met both targets. Of the surface replacement
      arthroplasties, 181 (69%) met the abduction target, 247 (94%) met the anteversion
      target, and 172 (65%) simultaneously met both targets. Low-volume surgeons were
      2.16 times more likely to miss target component position compared with high
      volume surgeons (p = 0.002). The odds of missing the target increased by >= 0.2
      for every 5 kg/m2 increase in body mass index. Minimally invasive approaches,
      diagnosis, years of surgical experience, femoral head size, and age of the
      patient did not affect component position. CONCLUSIONS: Increased odds of
      component malposition were found with lower-volume surgeons and higher body mass
      index. No other variables had a significant effect on component placement. LEVEL
      OF EVIDENCE: Therapeutic Level III. See Instructions for Authors for a complete
      description of levels of evidence.

PMID- 24088969
TI  - Articular congruity is associated with short-term clinical outcomes of
      operatively treated SER IV ankle fractures.
AB  - BACKGROUND: With regard to supination-external rotation type-IV (SER IV) ankle
      fractures, there is no consensus regarding which patient, injury, and treatment
      variables most strongly influence clinical outcome. The purpose of this
      investigation was to examine the impact of articular surface congruity on the
      functional outcomes of operatively treatment of SER IV ankle fractures. METHODS:
      A prospectively generated database consisting of operatively treated SER IV ankle
      fractures was reviewed. Postoperative computed tomography (CT) scans were used to
      assess ankle joint congruity. Ankles were considered incongruent in the presence
      of >2 mm of articular step-off, intra-articular loose bodies, or an articular
      surface gap of >2 mm (despite an otherwise anatomic reduction) due to joint
      impaction and comminution. Patients with at least one year of clinical follow-up
      were eligible for analysis. The primary and secondary outcome measures were the
      Foot and Ankle Outcome Score (FAOS) and ankle motion. RESULTS: One hundred and
      eight SER IV fractures met our inclusion criteria. The average duration of follow
      up was twenty-one months. Seventy-two patients (67%) had a congruent ankle joint,
      and thirty-six (33%) had elements of articular surface incongruity on
      postoperative CT scanning. These two groups were similar with regard to
      comorbidities and injury and treatment variables. At the time of the final follow
      up, the group with articular incongruity had a significantly worse FAOS with
      regard to symptoms (p = 0.012), pain (p = 0.004), and activities of daily living
      (p = 0.038). Those with articular incongruity had worse average scores in the
      FAOS sport domain as well. No significant differences in ankle motion were found
      between the two groups. CONCLUSIONS: In this population of patients with an
      operatively treated SER IV ankle fracture, the presence of postoperative
      articular incongruity correlated with inferior early clinical outcomes.
      Orthopaedic surgeons should scrutinize ankle fracture reductions and strive for
      perfection to allow for the best possible clinical outcome. LEVEL OF EVIDENCE:
      Therapeutic Level IV. See Instructions for Authors for a complete description of
      levels of evidence.

PMID- 24088970
TI  - Predictors of perioperative blood loss in total joint arthroplasty.
AB  - UPDATE The print version of this article has errors that have been corrected in
      the online version of this article. In the Materials and Methods section, the
      sentence that reads as "During the study period, our institution offered
      preoperative autologous blood donation to all patients who were scheduling for
      total joint arthroplasty with a hemoglobin level of no less than 11 mg/dL or a
      hematocrit level of at least 33%." in the print version now reads as "During the
      study period, our institution offered preoperative autologous blood donation to
      all patients who were scheduling for total joint arthroplasty with a hemoglobin
      level of no less than 11 g/dL or a hematocrit level of at least 33%." in the
      online version. In Table III, the footnote that reads as "The values are given as
      the estimate and the standard error in milligrams per deciliter." in the print
      version now reads as "The values are given as the estimate and the standard error
      in grams per deciliter." in the online version. BACKGROUND: Despite advances in
      surgical and anesthetic techniques, lower-extremity total joint arthroplasty is
      associated with considerable perioperative blood loss. As predictors of
      perioperative blood loss and allogenic blood transfusion have not yet been well
      defined, the purpose of this study was to identify clinical predictors for
      perioperative blood loss and allogenic blood transfusion in patients undergoing
      total joint arthroplasty. METHODS: From 2000 to 2008, all patients undergoing
      unilateral primary total hip or knee arthroplasty who met the inclusion criteria
      were enrolled in the study. Perioperative blood loss was calculated with use of a
      previously validated formula. The predictors of perioperative blood loss and
      allogenic blood transfusion were identified in a multivariate analysis. RESULTS:
      Eleven thousand three hundred and seventy-three patients who underwent total
      joint arthroplasty, including 4769 patients who underwent total knee arthroplasty
      and 6604 patients who underwent total hip arthroplasty, were evaluated.
      Multivariate analysis indicated that an increase in blood loss was associated
      with being male (263.59 mL in male patients who had undergone total hip
      arthroplasty and 233.60 mL in male patients who had undergone total knee
      arthroplasty), a Charlson Comorbidity Index of >3 (293.99 mL in patients who had
      undergone total hip arthroplasty and 167.96 mL in patients who had undergone
      total knee arthroplasty), and preoperative autologous blood donation (593.51 mL
      in patients who had undergone total hip arthroplasty and 592.30 mL in patients
      who had undergone total knee arthroplasty). In patients who underwent total hip
      arthroplasty, regional anesthesia compared with general anesthesia reduced the
      amount of blood loss. The risk of allogenic blood transfusion increased with the
      amount of blood loss in the patients who underwent total hip arthroplasty (odds
      ratio, 1.43 [95% confidence interval, 1.40 to 1.46]) and the patients who
      underwent total knee arthroplasty (odds ratio, 1.47 [95% confidence interval,
      1.42 to 1.51]), but the risk of blood transfusion increased with the Charlson
      Comorbidity Index only in patients who underwent total knee arthroplasty (odds
      ratio, 3.2 [95% confidence interval, 1.99 to 5.15]). The risk of allogenic blood
      transfusion decreased with preoperative autologous blood donation in patients who
      underwent total hip arthroplasty (odds ratio, 0.01 [95% confidence interval, 0.01
      to 0.02]) and patients who underwent total knee arthroplasty (odds ratio, 0.02
      [95% confidence interval, 0.01 to 0.03]). CONCLUSIONS: This study identified some
      clinical predictors for blood loss in patients undergoing total joint
      arthroplasty that we believe can be used for implementing more effective blood
      conservation strategies. LEVEL OF EVIDENCE: Prognostic Level IV. See Instructions
      for Authors for a complete description of levels of evidence.

PMID- 24088971
TI  - Cross-sectional area of the supraspinatus muscle after rotator cuff repair: an
      anatomic measure of outcome.
AB  - BACKGROUND: The change in the cross-sectional area of a repaired muscle, measured
      with use of magnetic resonance imaging (MRI), could be an indicator of recovery
      of muscle function. The aims of this study were to evaluate the change in the
      area of the supraspinatus muscle between the immediately postoperative and one
      year postoperative MRIs and to identify factors associated with the change.
      METHODS: Eighty-eight patients with a full-thickness rotator cuff tear were
      included. MRI was performed three days and one year after surgery. Patients were
      classified into two groups according to whether the area of the supraspinatus
      increased or decreased between these two time points. Outcomes including pain,
      shoulder motion, strength, and commonly used clinical scores were assessed
      preoperatively and at three, six, and twelve months after surgery. Changes in the
      rotator cuff muscles and retear of the repaired tendon were also evaluated.
      RESULTS: The area of the supraspinatus muscle increased in twenty-nine (33%) of
      the patients and decreased in fifty-nine (67%). The change in area was 36.75 +/-
      27.94 mm2 in the group in which it increased and -94.25 +/- 70.38 mm2 in the
      group in which it decreased (p < 0.001). Multiple regression analysis indicated
      that a lower preoperative Simple Shoulder Test (SST) score, better gross visual
      grade of the tendon at surgery, and greater strength of the supraspinatus at six
      months postoperatively were associated with an increase in the area. No retear or
      Sugaya grade of 3 was found in any patient in whom the area increased, whereas
      34% of the patients in whom the area decreased had a retear (p < 0.001).
      CONCLUSIONS: This study showed that the cross-sectional area of the supraspinatus
      muscle could either increase or decrease during the first year after rotator cuff
      repair and that robust healing (indicated by a Sugaya grade of 1 or 2) and good
      tendon quality at surgery were important factors associated with an increase in
      the area. LEVEL OF EVIDENCE: Prognostic Level II. See Instructions for Authors
      for a complete description of levels of evidence.

PMID- 24088972
TI  - Development and testing of an expectations survey for patients undergoing lumbar
      spine surgery.
AB  - BACKGROUND: Patients' expectations of lumbar spine surgery have not been obtained
      with valid and reliable scales derived from patients' perspectives. The objective
      of this cross-sectional study was to develop and to test a patient-derived
      expectations survey. METHODS: The survey was developed in three phases. Phase 1
      involved interviews with patients with open-ended questions about expectations
      and assembly of a draft survey. Phase 2 involved administering the survey twice
      to assess test-retest reliability. Phase 3 involved selection of final items
      based on concordance of responses and clinical relevance, and the development of
      a scoring rubric. RESULTS: In Phase 1, 118 preoperative patients with diverse
      lumbar spine diagnoses volunteered 583 expectations, from which thirty-one
      discrete categories were discerned and became the items for the draft survey. In
      Phase 2, another fifty-six preoperative patients completed the draft survey
      twice, four days apart. In Phase 3, twenty-one items were retained for the final
      survey addressing symptom relief, return to basic mobility, resumption of
      activities, and improvement in psychosocial well-being. An overall score was
      calculated on the basis of the number of expectations and amount of improvement
      expected and ranged from 0 to 100 points; a higher score indicates more
      expectations. For patients in Phase 2, the mean scores for both administrations
      were 66 and 65 points, the Cronbach alpha coefficients for both administrations
      were 0.90 and 0.92, and the intraclass correlation coefficient between scores was
      0.86. CONCLUSIONS: We developed a patient-derived survey that is valid, reliable,
      and applicable to diverse diagnoses and includes physical and psychosocial
      expectations. The survey generates an overall score that is easy to calculate and
      to interpret, and thus fills a gap in the assessment of lumbar spine surgery by
      offering a practical and comprehensive way to record patients' expectations.

PMID- 24088973
TI  - Prevention of venous thromboembolic disease after total hip and knee
      arthroplasty.
AB  - The selection of a regimen for venous thromboembolic prophylaxis after total
      joint arthroplasty is a balance between efficacy and safety. Bleeding may have a
      negative impact on clinical outcomes. Recently, both the American Academy of
      Orthopaedic Surgeons (AAOS) and the American College of Chest Physicians (ACCP)
      developed new evidence-based guidelines for venous thromboembolic prophylaxis
      after total joint arthroplasty. On the basis of a review of the available
      literature, the AAOS guideline panel was unable to make a recommendation with
      respect to the selection of a specific prophylaxis regimen or duration of
      prophylaxis following routine total joint arthroplasty. The ACCP panel
      recommended one of the following modalities as prophylaxis (rather than no
      prophylaxis at all) for a minimum of fourteen days: warfarin, low-molecular
      weight heparin, fondaparinux, aspirin, rivaroxaban, dabigatran, apixaban, or
      portable mechanical compression. Both the AAOS and the ACCP guidelines
      recommended against screening with postoperative duplex ultrasonography at the
      time of discharge after routine total joint arthroplasty. There is renewed
      interest in the use of mechanical compression as prophylaxis with the advent of
      portable compression devices, which allow continuation of this type of
      prophylaxis after hospital discharge. Although the early data are promising,
      appropriately powered randomized trials are needed to determine the efficacy of
      the devices compared with other prophylaxis regimens.

PMID- 24088975
TI  - Quantitative and qualitative assessment of bone perfusion and arterial
      contributions in a patellar fracture model using gadolinium-enhanced magnetic
      resonance imaging: a cadaveric study.
AB  - BACKGROUND: The purpose of the present study was to evaluate the anatomy and
      contribution of the patellar vascular supply and to quantify the effect of a
      transverse fracture on patellar perfusion. METHODS: In twenty matched pairs of
      fresh-frozen cadaveric knees, the superficial femoral artery, anterior tibialis
      artery, and posterior tibialis artery were cannulated. One side of each matched
      pair was randomly selected to undergo one of two osteotomies: (1) midpatellar
      osteotomy or (2) distal-pole osteotomy. For volumetric analysis, comparisons were
      performed between contrast-enhanced magnetic resonance images and precontrast
      magnetic resonance images as well as between osteotomized patellar bone fragments
      and the corresponding intact areas on the control side. We then injected a
      urethane polymer compound and dissected all specimens to examine extraosseous
      vascularity. RESULTS: Magnetic resonance imaging demonstrated that the largest
      arterial contribution to the patella entered at the inferior pole in 100% of the
      specimens; in 80% of these specimens, the artery entered inferomedially. It also
      revealed an overall decrease in contrast enhancement in both transverse osteotomy
      groups, with an average reduction in enhancement in the proximal fragment of 36%.
      CONCLUSIONS: If possible, surgical interventions about the knee should be
      carefully planned to preserve the peripatellar ring (the source of the entire
      patellar blood supply), especially the inferior patellar network. Distal-pole
      patellectomy should be avoided to retain vascularized bone at the reduced
      fracture site.

PMID- 24088976
TI  - Fixation of high-flexion total knee prostheses: five-year follow-up results of a
      four-arm randomized controlled clinical and roentgen stereophotogrammetric
      analysis study.
AB  - BACKGROUND: High-flexion total knee arthroplasty was introduced to meet the
      demands of daily activity requiring increased knee flexion. However, concerns
      have been raised regarding the fixation of high-flexion total knee arthroplasty
      components and increased rates of loosening have been reported. To date,
      migration, and thus fixation, of high-flexion total knee arthroplasty components
      has not been analyzed and the preferential bearing type (mobile or fixed) is
      unknown. METHODS: Of eighty-six consecutive eligible patients, seventy-four
      patients (seventy-eight knees) scheduled for total knee arthroplasty were
      randomized to one of four Legacy Posterior Stabilized (LPS) total knee prosthesis
      designs: (1) LPS-Flex mobile, (2) LPS-Flex fixed, (3) LPS mobile, and (4) LPS
      fixed. The primary outcome was component migration measured with use of Roentgen
      stereophotogrammetric analysis, and secondary outcomes were postoperative knee
      flexion and extension and Knee Society Score. Patients were evaluated
      postoperatively at six, twelve, twenty-six, and fifty-two weeks and annually
      thereafter. At the five-year follow-up, eight patients had died and two patients
      were lost to follow-up. Seventy-seven tibial and forty-two femoral components
      were suitable for migration measurements. RESULTS: The overall five-year
      migration of the seventy-seven tibial components was not significantly different
      among the four total knee prosthesis designs (compared with the LPS fixed design,
      the range of overall mean differences for the other three designs was 0.02 to
      0.25 mm) and migration was comparable at the two and five-year follow-up.
      Migration stabilized in all but three components (two LPS-Flex mobile and one LPS
      fixed); one of these components has already been revised and was aseptically
      loose. The overall five-year migration of the forty-two femoral components was
      comparable among the four designs (compared with the LPS fixed design, the range
      of overall mean differences for the other three designs was 0.01 to 0.18 mm) and
      was similar at two and five years postoperatively. One femoral component (LPS
      Flex mobile) migrated excessively. In patients who had a mean postoperative
      flexion of >= 125 degrees  or a maximum flexion of >= 135 degrees  during the one
      to five-year follow-up period, migration of high-flexion components was
      comparable with that of conventional components and indicative of appropriate
      fixation. Postoperative flexion, extension, Knee Society Score, and Knee Society
      Score function were comparable during the five-year follow-up period and at the
      two and five-year follow-up. CONCLUSIONS: The LPS-Flex total knee prosthesis with
      either a mobile or a fixed bearing had migration comparable that of with its
      conventional counterpart and is expected to have similar (excellent) long-term
      survival in these patients. LEVEL OF EVIDENCE: Therapeutic Level I. See
      Instructions for Authors for a complete description of levels of evidence.

PMID- 24088974
TI  - Low-energy fractures without low T-scores characteristic of osteoporosis: a
      possible bone matrix disorder.
AB  - BACKGROUND: Osteoporotic fractures commonly occur after low-energy trauma in
      postmenopausal women with reduced bone quantity documented by low bone mineral
      density (BMD). Low-energy fractures, however, have also been reported to occur in
      premenopausal women with normal or near-normal BMD, suggesting the existence of a
      bone quality abnormality. METHODS: Bone quality and quantity were evaluated in a
      cross-sectional study of three groups of premenopausal white females: (1) twenty
      five subjects with low-energy fracture(s) and BMD in the normal range (t-scores >
      -2.0), (2) eighteen subjects with low-energy fracture(s) and BMD in the
      osteoporotic range (t-scores <= -2.5), and (3) fourteen healthy volunteers
      (controls). Bone quality was assessed with use of Fourier transform infrared
      spectroscopy and histomorphometry in iliac crest bone samples obtained from all
      subjects; bone quantity was assessed by dual x-ray absorptiometry and
      histomorphometry. RESULTS: The collagen crosslinking ratio in the non-low-BMD
      subjects with fractures was 13% greater than the ratio in the low-BMD subjects
      with fractures and 14% greater than the ratio in the controls (p < 0.001 for
      both). Cancellous bone volume was 29% greater (p < 0.01) and trabecular
      separation was 31% less (p < 0.01) in the non-low-BMD subjects with fractures
      than in the low-BMD subjects with fractures; the values in the non-low-BMD
      subjects did not differ from those in the controls. Bone turnover did not differ
      among the groups, and osteomalacia was not present in any subject. Thus, the non
      low-BMD subjects with fractures maintained bone quantity, but the collagen
      crosslinking ratio, a parameter of bone quality, was abnormal. In contrast, the
      low-BMD subjects with fractures did not have this collagen crosslinking
      abnormality but did have abnormal bone quantity. CONCLUSIONS: This study
      highlights a collagen crosslinking abnormality in patients with low-energy
      fractures and nonosteoporotic t-scores. Reports have indicated that altered
      collagen crosslinking is associated with subnormal fracture resistance. A finding
      of nonosteoporotic bone mass in a patient with low-energy fractures would justify
      assessment of bone material quality, which currently requires a bone biopsy.
      Further studies are needed to search for possible noninvasive tests to diagnose
      abnormal crosslinking. Since no specific therapies for abnormal collagen
      crosslinking are currently available, studies are also needed to explore novel
      therapeutic modalities to reverse the underlying collagen crosslinking
      abnormality. LEVEL OF EVIDENCE: Prognostic Level III. See Instructions for
      Authors for a complete description of levels of evidence.

PMID- 24088977
TI  - A ten-year analysis of the research funding program of the orthopaedic trauma
      association.
AB  - BACKGROUND: The Orthopaedic Trauma Association (OTA) awarded over $3 million in
      research grants during 2000 through 2009. However, little is known regarding the
      outcomes of this funding program. Given the continued constraints in securing
      research dollars, we evaluated the research funding program of the OTA over this
      ten-year period. We studied the association of grant funding with (1) the
      publication rate, (2) the cost per publication, (3) the journal impact factor for
      published manuscripts, and (4) the dollar amount of extramural funding secured.
      METHODS: Grants from the target period were identified with use of the OTA online
      archive. The title of each grant and the name of the principal investigator were
      used to search across seven scientific databases for associated publications.
      RESULTS: Over the study period, $3,507,050 was awarded through 131 grants (thirty
      three clinical, thirty-nine basic science, and fifty-nine resident). A total of
      202 associated publications (seventy-three for the clinical grants, eighty-four
      for the basic science grants, and forty-five for the resident grants) were
      identified. Twenty-two (67%) of the clinical grants led to at least one
      publication compared with thirty-one (79%) of the basic science grants and twenty
      four (41%) of the resident grants. The cost per publication was $26,892 for the
      clinical grants compared with $11,357 for the basic science grants and $13,111
      for the resident grants. The mean impact factor of the journals containing the
      publications was 2.58. CONCLUSIONS: Over the study period, the publication output
      for the funded projects was substantial. Basic science grants had the highest
      publication rate. The three types of grants resulted in publication in peer
      reviewed journals with similar impact factors.

PMID- 24088978
TI  - Those who can, do-those who can, teach: AOA critical issues.

PMID- 24088979
TI  - Residents' perceptions of sex diversity in orthopaedic surgery.
AB  - BACKGROUND: Sex diversity in orthopaedic surgery lags behind other surgical
      specialties. Women comprise 13.2% of orthopaedic residents and 15% of full-time
      faculty, despite 47.8% of graduating medical students being women. The purposes
      of this study were to demonstrate how orthopaedic surgery has been less
      successful in recruiting women compared with general surgery and to identify the
      sex-specific factors that influenced orthopaedic surgery residents to choose
      their specialty. METHODS: A search of graduate medical data was performed to
      compare the recruitment of women into orthopaedic and general surgery. Next, a
      seven-question survey was e-mailed to 2629 orthopaedic residents by the American
      Academy of Orthopaedic Surgeons. Questions were formulated to detect why
      orthopaedic surgery residents chose their specialty. Data were collected over six
      weeks and responses were analyzed with use of one-tailed t tests to make
      comparisons of responses on the basis of sex. RESULTS: The historical data search
      showed that the percentage of female representation in both orthopaedic and
      general surgery has increased since 1968, but it has increased significantly
      faster in general surgery than in orthopaedic surgery (p < 0.0001). Five hundred
      and twenty-nine (20%) of the 2629 orthopaedic surgery residents who were
      contacted responded to the survey. Of the respondents, 114 (22%) were female and
      415 (78%) were male. Several significant differences were found in the responses
      between the sexes. These include the timing of the decision to enter orthopaedic
      surgery and positive influences in choosing orthopaedic surgery as a specialty.
      Additionally, women, significantly more than men, believed that more of their
      peers entered general surgery because of greater acceptance by senior faculty in
      that field (p < 0.0001). CONCLUSIONS: To our knowledge, this study is the first
      to survey residents on their perceptions of orthopaedic surgery and to identify
      factors that may hinder the recruitment of women into orthopaedic surgery. Our
      data show that increased exposure to orthopaedic content during medical school
      and increased female mentorship may help recruit more women into the orthopaedic
      surgery workforce.

PMID- 24088980
TI  - Judgments about deservingness.
AB  - A twenty-one-year-old known gang member presented to the emergency room late on a
      Friday night with multiple gunshot wounds, including one to his hand, with
      multiple open fractures and extensive soft-tissue injury. After evaluation by the
      on-call resident, the orthopaedic attending physician was notified and the
      decision was made to bring the patient to the operating room for surgical
      treatment.Due to the extensive nature of the trauma, the surgical reconstruction
      took several hours. In the middle of the operation, one member of the operating
      room staff began to complain about the late hour and commented that the surgeon
      need not be so meticulous as the patient was not going to use the hand to play
      piano; he would likely be using it to shoot a gun. The attending physician
      replied that we could not know whether or not the patient played piano, nor
      whether he might take it up after surgery. The surgery was completed, and the
      patient was brought to the intensive care unit for postoperative monitoring of
      his other injuries. 

PMID- 24088981
TI  - Time to reconsider.

PMID- 24088982
TI  - More evidence that volar locked plating for distal radial fractures does not
      offer a functional advantage over traditional treatment options.

PMID- 24088983
TI  - Are the growing pains finally over?

PMID- 24088984
TI  - Condensin I associates with structural and gene regulatory regions in vertebrate
      chromosomes.
AB  - The condensin complex is essential for correct packaging and segregation of
      chromosomes during mitosis and meiosis in all eukaryotes. To date, the genome
      wide location and the nature of condensin-binding sites have remained elusive in
      vertebrates. Here we report the genome-wide map of condensin I in chicken DT40
      cells. Unexpectedly, we find that condensin I binds predominantly to promoter
      sequences in mitotic cells. We also find a striking enrichment at both
      centromeres and telomeres, highlighting the importance of the complex in
      chromosome segregation. Taken together, the results show that condensin I is
      largely absent from heterochromatic regions. This map of the condensin I binding
      sites on the chicken genome reveals that patterns of condensin distribution on
      chromosomes are conserved from prokaryotes, through yeasts to vertebrates. Thus
      in three kingdoms of life, condensin is enriched on promoters of actively
      transcribed genes and at loci important for chromosome segregation. 

PMID- 24088985
TI  - Mutationally activated Rho GTPases in cancer.
AB  - The Rho family of GTPases (members of the Ras superfamily) are best known for
      their roles in regulating cytoskeletal dynamics. It is also well established that
      misregulation of Rho proteins contributes to tumorigenesis and metastasis. Unlike
      Ras proteins, which are frequently mutated in cancer (around 30%), Rho proteins
      themselves are generally not found to be mutated in cancer. Rather, misregulation
      of Rho activity in cancer was thought to occur by overexpression of these
      proteins or by misregulation of molecules that control Rho activity, such as
      activation or overexpression of GEFs and inactivation or loss of GAPs or GDIs.
      Recent studies, enabled by next-generation tumor exome sequencing, report
      activating point mutations in Rho GTPases as driver mutations in melanoma, as
      well as breast, and head and neck cancers. The Rac1(P29L) mutation identified in
      these tumor studies was previously identified by our lab as an activating Rac
      mutation in C. elegans neuronal development, highlighting the conserved nature of
      this mutation. Furthermore, this finding supports the relevance of studying Rho
      GTPases in model organisms such as C. elegans to study the mechanisms that
      underlie carcinogenesis. This review will describe the recent findings that
      report activating Rho mutations in various cancer types, moving Rho GTPases from
      molecules misregulated in cancer to mutagenic targets that drive tumorigenesis. 

PMID- 24088987
TI  - Can peripheral blood mononuclear cells be used as a proxy for mitochondrial
      dysfunction in vital organs during hemorrhagic shock and resuscitation?
AB  - INTRODUCTION: Although mitochondrial dysfunction is thought to contribute to the
      development of posttraumatic organ failure, current techniques to assess
      mitochondrial function in tissues are invasive and clinically impractical. We
      hypothesized that mitochondrial function in peripheral blood mononuclear cells
      (PBMCs) would reflect cellular respiration in other organs during hemorrhagic
      shock and resuscitation. METHODS: Using a fixed-pressure HS model, Long-Evans
      rats were bled to a mean arterial pressure of 40 mmHg. When blood pressure could
      no longer be sustained without intermittent fluid infusion (decompensated HS),
      lactated Ringer's solution was incrementally infused to maintain the mean
      arterial pressure at 40 mmHg until 40% of the shed blood volume was returned
      (severe HS). Animals were then resuscitated with 4* total shed volume in lactated
      Ringer's solution over 60 min (resuscitation). Control animals underwent the same
      surgical procedures, but were not hemorrhaged. Animals were randomized to control
      (n = 6), decompensated HS (n = 6), severe HS (n = 6), or resuscitation (n = 6)
      groups. Kidney, liver, and heart tissues as well as PBMCs were harvested from
      animals in each group to measure mitochondrial oxygen consumption using high
      resolution respirometry. Flow cytometry was used to assess mitochondrial membrane
      potential (Psim) in PBMCs. One-way analysis of variance and Pearson correlations
      were performed. RESULTS: Mitochondrial oxygen consumption decreased in all
      tissues, including PBMCs, following decompensated HS, severe HS, and
      resuscitation. However, the degree of impairment varied significantly across
      tissues during hemorrhagic shock and resuscitation. Of the tissues investigated,
      PBMC mitochondrial oxygen consumption and Psim provided the closest correlation
      to kidney mitochondrial function during HS (complex I: r = 0.65; complex II: r =
      0.65; complex IV: r = 0.52; P < 0.05). This association, however, disappeared
      with resuscitation. A weaker association between PBMC and heart mitochondrial
      function was observed, but no association was noted between PBMC and liver
      mitochondrial function. CONCLUSIONS: All tissues including PBMCs demonstrated
      significant mitochondrial dysfunction following hemorrhagic shock and
      resuscitation. Although PBMC and kidney mitochondrial function correlated well
      during hemorrhagic shock, the variability in mitochondrial response across
      tissues over the spectrum of hemorrhagic shock and resuscitation limits the
      usefulness of using PBMCs as a proxy for tissue-specific cellular respiration.

PMID- 24088990
TI  - Aquaporin 1 and 5 expression evoked by the beta2 adrenoreceptor agonist
      terbutaline and lipopolysaccharide in mice and in the human monocytic cell line
      THP-1 is differentially regulated.
AB  - Aquaporin 1 (AQP1) and AQP5 expression may impact on key mechanisms in sepsis.
      However, it is unclear whether these AQPs are expressed to an equal extent or
      regulated differentially. Accordingly, we investigated the time-dependent
      expression of AQP1 and AQP5 following stimulation with lipopolysaccharide (LPS)
      in cultured human THP-1 cells and in the lungs of mice injected with LPS.
      Furthermore, we tested the hypothesis that the beta2 adrenoreceptor agonist
      terbutaline or its downstream effector cyclic adenosine monophosphate (cAMP)
      mitigates LPS-evoked changes of AQP expression. THP-1 cells were stimulated with
      either LPS (1 MUg/mL; serotype O127:B8), 8-Br-cAMP (1 mM), or both, and RNA and
      protein were extracted at baseline and after 2, 6, and 24 h. C57BL/6 mice that
      received LPS (20 mg/kg i.p.), terbutaline (2.5 mg/kg), or both were killed 8 h
      later, and lungs were excised for RNA extraction and lung wet weight
      determination. Real-time polymerase chain reaction and Western blot analysis show
      that LPS increased AQP1 (3 h, P < 0.0001) but not AQP5 mRNA and protein
      expression in THP-1 cells. cAMP increased AQP1 (6 h, P < 0.0001) but not AQP5
      mRNA and protein expression. Incubation with both substances accelerated the
      increase in AQP1 (2 h, P = 0.001) expression, whereas AQP5 expression decreased
      after 2 h but increased after 24 h (P = 0.0148). In mice lungs, LPS decreased
      AQP1 (P = 0.0082) but not AQP5 mRNA expression and increased lung wet weight.
      Terbutaline increased AQP1 mRNA expression twice (P = 0.0005) but not AQP5 mRNA
      expression. Terbutaline did neither abolish the LPS-induced decrease in AQP1 and
      AQP5 expression nor increase lung weight. Thus, AQP1 and AQP5 expression is
      differentially regulated following exposure to LPS, the beta2 adrenoreceptor
      agonist terbutaline, and cAMP. Furthermore, neither terbutaline nor cAMP
      mitigated the LPS-evoked change of AQP1 and AQP5 expression. 

PMID- 24088992
TI  - A perspective on mesenchymal stromal cell transplantation in the treatment of
      sepsis.
AB  - Although a variety of disease-modifying agents have been studied as potential
      sepsis treatments, no beneficial effects on the course of sepsis, in terms of
      survival, have been observed until now. Because of their plasticity, mesenchymal
      stromal cells (MSCs) have been implicated as an effective novel therapy modality
      for various diseases and are widely used for cellular therapies and tissue
      engineering. The existing knowledge supports the idea that MSCs might be
      beneficial in sepsis treatment. Our objective was to selectively address the
      evidence, based on multistep processes, supporting the potential of MSC-based
      therapies in clinical sepsis trials. In this study, we performed a stepwise
      approach to defend the evaluation of MSC treatments for sepsis from the bench to
      the bedside. Altogether, the reviewed data postulate that the signals produced by
      inflamed tissues might determine the functional effects of MSCs. These effects
      include bacterial clearance, suppression of inflammation, antiapoptosis, or
      stimulation of regenerative responses. We conclude that the clinical application
      of MSCs is a feasible and well-tolerated approach and therefore may have benefits
      for patients with sepsis. 

PMID- 24088989
TI  - Role of biomarkers in sepsis care.
AB  - Sepsis is one of the leading causes of mortality and morbidity, even with the
      current availability of extended-spectrum antibiotics and advanced medical care.
      Biomarkers offer a tool in facilitating early diagnosis, in identifying patient
      populations at high risk of complications, and in monitoring progression of the
      disease, which are critical assessments for appropriate therapy and improvement
      in patient outcomes. Several biomarkers are already available for clinical use in
      sepsis; however, their effectiveness in many instances is limited by the lack of
      specificity and sensitivity to characterize the presence of an infection and the
      complexity of the inflammatory and immune processes and to stratify patients into
      homogenous groups for specific treatments. Current advances in molecular
      techniques have provided new tools facilitating the discovery of novel
      biomarkers, which can vary from metabolites and chemical products present in body
      fluids to genes and proteins in circulating blood cells. The purpose of this
      review was to examine the current status of sepsis biomarkers, with special
      emphasis on emerging markers, which are undergoing validation and may transition
      into clinical practice for their informative value in diagnosis, prognosis, or
      response to therapy. We will also discuss the new concept of combination
      biomarkers and biomarker risk models, their existing challenges, and their
      potential use in the daily management of patients with sepsis. 

PMID- 24088993
TI  - Prehospital hypertonic saline resuscitation attenuates the activation and
      promotes apoptosis of neutrophils in patients with severe traumatic brain injury.
AB  - BACKGROUND: Activation of polymorphonuclear neutrophils (PMNs) is thought to
      contribute to traumatic brain injury (TBI). Since hypertonic fluids can inhibit
      PMN activation, we studied whether hypertonic fluid resuscitation can reduce
      excessive PMN activation in TBI patients. METHODS: Trauma patients with severe
      TBI were resuscitated with 250 mL of either 7.5% hypertonic saline (HS; n = 22),
      HS + 6% dextran-70 (HSD; n = 22), or 0.9% normal saline (NS; n = 39), and blood
      samples were collected on hospital admission and 12 and 24 h after resuscitation.
      Polymorphonuclear neutrophil activation (CD11b, CD62L, CD64) and degranulation
      (CD63, CD66b, CD35) markers and oxidative-burst activity, as well as spontaneous
      PMN apoptosis were measured by flow cytometry. RESULTS: Relative to healthy
      controls, TBI patients showed increased PMN activation and decreased apoptosis of
      PMNs. In the HS group, but not in the HSD group, markers of PMN adhesion (CD11b,
      CD64) and degranulation (CD35, CD66b) were significantly lower than those in the
      NS group. These effects were particularly pronounced 12 h after resuscitation.
      Treatment with HS and HSD inhibited PMN oxidative burst responses compared with
      NS-treated patients. Hypertonic saline alone partially restored delayed PMN
      apoptosis. Despite these differences, the groups did not differ in clinical
      outcome parameters such as mortality and Extended Glasgow Outcome Scale.
      CONCLUSIONS: This study demonstrates that prehospital resuscitation with HS can
      partially restore normal PMN activity and the apoptotic behavior of PMNs, whereas
      resuscitation with HSD was largely ineffective. Although the results are
      intriguing, additional research will be required to translate these effects of HS
      into treatment strategies that improve clinical outcome in TBI patients.

PMID- 24088995
TI  - Intrapleural steroid instillation for multiple organ failure with acute
      respiratory distress syndrome.
AB  - Acute respiratory distress syndrome (ARDS) increases mortality in patients with
      multiorgan dysfunction syndrome (MODS). This study evaluates the feasibility of
      intrapleural steroid instillation (IPSI) in patients with ARDS and MODS
      unresponsive to conventional extracorporeal membrane oxygenation (ECMO). Ninety
      two of 467 patients who underwent ECMO between 2005 and 2009 had ARDS, and 30
      consecutive adult patients of these 92 patients with severe ARDS and MODS were
      retrospectively analyzed in this study. Nine of these 30 patients, who did not
      respond to therapy and whose condition deteriorated, were managed with IPSI. All
      patients met the inclusion criteria of hemodynamic instability with high
      catecholamine infusion requirement and 100% oxygen demand in ventilation and ECMO
      flow. On initial diagnosis of ARDS, no differences in prognostic scorings were
      observed in patients who underwent conventional treatment (n = 21) and those who
      underwent IPSI (n = 9). Blood oxygenation, tidal volume, changing in chest
      radiographic findings, and survival rates were analyzed. The primary outcome was
      survival until discharge from the hospital. Pulmonary radiographic appearance
      improved after 3 days of IPSI treatment (P = 0.008); the ratio of arterial
      partial pressure of oxygen to fraction of inspired oxygen also increased
      significantly after 5 days of IPSI treatment (P = 0.028). Moreover, the 28-day
      mortality rate (P = 0.017), 60-day mortality rate (P = 0.003), and survival rate
      (78% vs. 19%; P = 0.003) significantly improved in patients undergoing IPSI,
      which therefore appears to be an easily implemented and highly effective
      treatment for patients with severe ARDS in combination with MODS, particularly in
      patients who fail to respond to conventional treatment. 

PMID- 24088994
TI  - Interleukin 6 mediates neuroinflammation and motor coordination deficits after
      mild traumatic brain injury and brief hypoxia in mice.
AB  - Traumatic brain injury (TBI) is a leading cause of mortality and disability.
      Acute postinjury insults after TBI, such as hypoxia, contribute to secondary
      brain injury and worse clinical outcomes. The functional and neuroinflammatory
      effects of brief episodes of hypoxia experienced following TBI have not been
      evaluated. Our previous studies have identified interleukin 6 (IL-6) as a
      potential mediator of mild TBI-induced pathology. In the present study, we sought
      to determine the effects of brief hypoxia on mild TBI and whether IL-6 played a
      role in the neuroinflammatory and functional deficits after injury. A murine
      model of mild TBI was induced by a weight drop (500 g from 1.5 cm). After injury,
      mice were exposed to immediate hypoxia (FIO2 = 15.1%) or normoxia (FIO2 = 21%)
      for 30 min. Serum and brain samples were analyzed for inflammatory cytokines 24 h
      after TBI. Neuron-specific enolase was measured as a serum biomarker of brain
      injury. Evaluation of motor coordination was performed for 5 days after TBI using
      a rotarod device. In some animals, anti-IL-6 was administered following TBI and
      hypoxia to neutralize systemic IL-6. Mice undergoing TBI had significant
      increases in brain injury. Exposure to brief hypoxia after TBI resulted in a more
      than 5-fold increase in serum neuron-specific enolase. This increase was
      associated with increases in serum and brain cytokine expression, suggesting that
      brief hypoxia exacerbates systemic and brain inflammation. Neutralization of IL-6
      suppressed postinjury neuroinflammation and neuronal injury. In addition, TBI and
      hypoxia induced significant motor coordination deficits that were completely
      abrogated by IL-6 blockade. Exposure to hypoxia after TBI induces
      neuroinflammation and brain injury. These changes can be mitigated by
      neutralization of systemic IL-6. Interleukin 6 blockade also corrected the TBI
      induced deficit in motor coordination. These data suggest that systemic IL-6
      modulates the degree of neuroinflammation and contributes to reduced motor
      coordination after mild TBI. 

PMID- 24088996
TI  - Shock state: an unrecognized and underestimated presentation of drug reaction
      with eosinophilia and systemic symptoms.
AB  - Some patients with drug reaction with eosinophilia and systemic symptoms (DRESS)
      are probably admitted in intensive care unit (ICU), but data concerning their
      clinical features at admission are scarce. Therefore, in the present study, we
      used a clinical network of French intensivists to study the clinical features and
      evolution of DRESS patients hospitalized in ICU. A national, retrospective,
      multicenter study collected DRESS cases hospitalized in ICU for DRESS from 2000
      to end of 2011. All files were analyzed through the RegiSCAR scoring system as
      "no," "possible," "probable," or "definite" DRESS. Patients were included only if
      they had a probable or definite DRESS. Demographic, hemodynamic, biological, and
      infectious data were recorded. Twenty-one patients were included. Hospital
      mortality was 10 (47%) of 21, and 16 of 21 patients had on admission a shock
      state necessitating vasopressor agents. Echocardiographic ejection fraction in
      shock patients was depressed (47% +/- 13%). Mechanical ventilation was required
      in 13 of 21 cases. Hepatic failure was observed in 11 of 21 cases, acute renal
      failure in 18 of 20 cases, and lactic acidosis in 12 of 20 patients. Initial
      bacteriology was negative in all patients. Human herpesvirus reactivations were
      found in five of 15 cases. In conclusion, shock without bacteriological
      documentation associated with multiple organ failure is the most common
      presentation of DRESS at admission in ICU and is associated with a higher
      mortality than previously described. 

PMID- 24088997
TI  - Neutrophils--a key component of ischemia-reperfusion injury.
AB  - Ischemia-reperfusion injury (IRI) is a common occurrence following myocardial
      infarction, transplantation, stroke, and trauma that can lead to multiple organ
      failure, which remains the foremost cause of death in critically ill patients.
      Current therapeutic strategies for IRI are mainly palliative, and there is an
      urgent requirement for a therapeutic that could prevent or reverse tissue damage
      caused by IRI. Neutrophils are the primary responders following ischemia and
      reperfusion and represent important components in the protracted inflammatory
      response and severity associated with IRI. Experimental studies demonstrate
      neutrophil infiltration at the site of ischemia and show that inducing
      neutropenia can protect organs from IRI. In this review, we highlight the
      mechanisms involved in neutrophil recruitment, activation, and adherence and how
      this contributes to disease severity in IRI. Inhibiting neutrophil mobilization,
      tissue recruitment, and ultimately neutrophil-associated activation of local and
      systemic inflammatory responses may have therapeutic potential in the
      amelioration of local and remote tissue damage following IRI. 

PMID- 24088998
TI  - Pancreatic digestive enzyme blockade in the small intestine prevents insulin
      resistance in hemorrhagic shock.
AB  - Hemorrhagic shock is associated with metabolic defects, including hyperglycemia
      and insulin resistance, but the mechanisms are unknown. We recently demonstrated
      that reduction of the extracellular domain of the insulin receptor by degrading
      proteases may lead to a reduced ability to maintain normal plasma glucose values.
      In shock, transfer of digestive enzymes from the lumen of the intestine into the
      systemic circulation after breakdown of the intestinal mucosal barrier causes
      inflammation and organ dysfunction. Suppression of the digestive enzymes in the
      lumen of the intestine with protease inhibitors is effective in reducing the
      level of the inflammatory reactions. To determine the degree to which blockade of
      digestive enzymes affects insulin resistance in shock, rats were exposed to acute
      hemorrhagic shock (mean arterial pressure of 30 mmHg for 2 h) at which time all
      shed blood volume was returned. Digestive proteases in the intestine were blocked
      with a serine protease inhibitor (tranexamic acid in polyethylene glycol and
      physiological electrolyte solution), and the density of the insulin receptor was
      measured with immunohistochemistry in the mesentery microcirculation. The
      untreated rat without enzyme blockade had significantly attenuated levels of
      insulin receptor density as compared with control and treated rats. Blockade of
      the digestive proteases after 60 min of hypotension in the lumen of the small
      intestine led to a lesser decrease in insulin receptor density compared with
      controls without protease blockade. Glucose tolerance test indicates a
      significant increase in plasma glucose levels 2 h after hemorrhagic shock, which
      are reduced to control values in the presence of protease inhibition in the lumen
      of the intestine. The transient reduction of the plasma glucose levels after an
      insulin bolus is significantly attenuated after shock but is restored when
      digestive enzymes in the lumen of the intestine are blocked. These results
      suggest that in hemorrhagic shock elevated microvascular extracellular digestive
      enzyme activity causes insulin receptor dysfunction, hyperglycemia, and reduced
      ability to regulate blood glucose values. 

PMID- 24088999
TI  - Postresuscitation treatment with argon improves early neurological recovery in a
      porcine model of cardiac arrest.
AB  - INTRODUCTION: Effects of postresuscitation treatment with argon on neurologic
      recovery were investigated in a porcine model of cardiac arrest (CA) with an
      underlying acute myocardial infarction. METHODS: The left anterior descending
      coronary artery was occluded in 12 pigs, and CA was induced. After 8 min of
      untreated CA, cardiopulmonary resuscitation was performed for 5 min before
      defibrillation. Following resuscitation, animals were subjected to 4-h
      ventilation with 70% argon/30% oxygen or 70% nitrogen/30% oxygen. Myocardial
      function was echocardiographically assessed, and serum neuron-specific enolase
      was measured. Animals were observed up to 72 h for assessment of survival and
      neurologic recovery. RESULTS: All the animals were resuscitated and survived for
      72 h, except for a control pig. Ventilation with argon did not have any
      detrimental effects on hemodynamics and respiratory gas exchange. All the six
      argon-treated animals had a fast and complete 72-h neurologic recovery, in
      contrast to only two of the six controls (P < 0.05). Seventy-two-hour neurologic
      alertness score and neurologic deficit score were, respectively, 100 and 0 in the
      argon group and 79 and 29 in the control one (P < 0.01 and P < 0.05).
      Significantly lower increases in serum neuron-specific enolase (12% vs. 234%) and
      minimal histological brain injury (neuronal degeneration: 0 vs. 1) were also
      observed in argon-treated animals, in comparison to controls. CONCLUSIONS: In
      this model, postresuscitation treatment with argon allowed for a faster and
      complete neurologic recovery, without detrimental effects on hemodynamics and
      respiratory gas exchanges.

PMID- 24089000
TI  - Freeze-dried plasma at the point of injury: from concept to doctrine.
AB  - While early plasma transfusion for the treatment of patients with ongoing major
      hemorrhage is widely accepted as part of the standard of care in the hospital
      setting, logistic constraints have limited its use in the out-of-hospital
      setting. Freeze-dried plasma (FDP), which can be stored at ambient temperatures,
      enables early treatment in the out-of-hospital setting. Point-of-injury plasma
      transfusion entails several significant advantages over currently used
      resuscitation fluids, including the avoidance of dilutional coagulopathy, by
      minimizing the need for crystalloid infusion, beneficial effects on endothelial
      function, physiological pH level, and better maintenance of intravascular volume
      compared with crystalloid-based solutions. The Israel Defense Forces Medical
      Corps policy is that plasma is the resuscitation fluid of choice for selected,
      severely wounded patients and has thus included FDP as part of its armamentarium
      for use at the point of injury by advanced life savers, across the entire
      military. We describe the clinical rationale behind the use of FDP at the point
      of-injury, the drafting of the administration protocol now being used by Israel
      Defense Forces advanced life support providers, the process of procurement and
      distribution, and preliminary data describing the first casualties treated with
      FDP at the point of injury. It is our hope that others will be able to learn from
      our experience, thus improving trauma casualty care around the world. 

PMID- 24089001
TI  - Conditional deletion of cardiomyocyte peroxisome proliferator-activated receptor
      gamma enhances myocardial ischemia-reperfusion injury in mice.
AB  - The nuclear transcription factor peroxisome proliferator-activated receptor gamma
      (PPARgamma) is a key regulator of the inflammatory response to an array of
      biologic insults. We have previously demonstrated that PPARgamma ligands reduce
      myocardial ischemia-reperfusion injury in rodents. In the current study, we
      directly determined the role of cardiomyocyte PPARgamma in ischemia-reperfusion
      injury, using a model of conditional cardiomyocyte-specific deletion of PPARgamma
      in vivo. In mice, alpha-myosin heavy chain-restricted Cre-mediated PPARgamma
      deficiency was induced by tamoxifen treatment (30 mg/kg intraperitoneally) for 4
      days (PPARgamma mice), whereas controls included mice treated with the oil
      diluent vehicle (PPARgamma mice). Western blot and histochemical analyses
      confirmed that expression of PPARgamma protein was abolished in cardiomyocytes of
      mice treated with tamoxifen, but not with vehicle. After tamoxifen or vehicle
      treatment, animals were subjected to 30-min ligation of the left anterior
      descending coronary artery followed by 2-h reperfusion. In PPARgamma mice,
      myocardial ischemia and reperfusion induced extensive myocardial damage, which
      was associated with elevated tissue activity of myeloperoxidase, indicating
      infiltration of neutrophils, and elevated plasma levels of troponin I when
      compared with PPARgamma mice. Upon echocardiographic analysis, PPARgamma mice
      also demonstrated ventricular dilatation and systolic dysfunction. Plasma levels
      of the proinflammatory cytokines interleukin 1beta and interleukin 6 were higher
      in PPARgamma mice when compared with PPARgamma mice. These pathological events in
      PPARgamma mice were associated with enhanced nuclear factor kappaB DNA binding in
      the infarcted hearts. Thus, our data suggest that cardiomyocyte PPARgamma is a
      crucial protective receptor and may prevent reperfusion injury by modulating
      mechanisms of inflammation. 

PMID- 24089002
TI  - Small doses of arginine vasopressin in combination with norepinephrine "buy" time
      for definitive treatment for uncontrolled hemorrhagic shock in rats.
AB  - Implementation of fluid resuscitation and blood transfusion are greatly limited
      in prehospital or evacuation settings after severe trauma or war wounds. With
      uncontrolled hemorrhagic shock rats, we investigated if arginine vasopressin
      (AVP) in combination with norepinephrine (NE) is independent (or slightly
      dependent) of fluid resuscitation and can "buy" time for the subsequently
      definitive treatment of traumatic hemorrhagic shock in the present study. The
      results showed that AVP (0.4 U/kg) alone or with NE (3 MUg/kg) with one-eighth
      and one-fourth volumes of total blood volume of lactated Ringer's infusion
      significantly increased and maintained the mean arterial pressure. Among all
      groups, 0.4 U/kg of AVP + NE (3 MUg/kg) with one-eighth volume of lactated
      Ringer's infusion had the best effect: it significantly increased and maintained
      hemodynamics and prolonged the survival time. This early treatment strategy
      significantly improved the effects of subsequently definitive treatments (after
      bleeding controlled): it increased the subsequent survival, improved the
      hemodynamic parameters, improved the cardiac function, and increased the tissue
      blood flow and oxygen delivery. These results suggested that early application of
      small doses of AVP (0.4 U/kg) + NE before bleeding control can "buy" time for the
      definitive treatment of uncontrolled hemorrhagic shock, which may be an effective
      measure for the early treatment of traumatic hemorrhagic shock. 

PMID- 24089003
TI  - Hydrocortisone reduces the beneficial effects of toll-like receptor 2 deficiency
      on survival in a mouse model of polymicrobial sepsis.
AB  - INTRODUCTION: Toll-like receptors (TLRs) play a crucial role in early host
      defense against microorganisms. Toll-like receptor 2 (TLR2) polymorphisms have a
      prevalence of 10%; functional defects of TLR2 are associated with higher
      susceptibility toward gram-positive bacteria, and TLR2 deficiency has been
      associated with an impaired adrenal stress response. In the present study, we
      compared endogenous corticosterone production of wild-type (WT) and TLR2
      deficient (TLR2) mice and analyzed survival after hydrocortisone therapy during
      sepsis induced by cecal ligation and puncture (CLP). METHODS: Male C57BL/6J (WT);
      and B6.129-Tlr2tm1Kir/J (TLR2) mice were subjected to CLP or sham operation and
      randomly assigned to postoperative treatment with either hydrocortisone (5 mg/kg)
      or vehicle (n = 10 mice/group). Survival was documented for an observation period
      of 48 h. Endogenous corticosterone production following hydrocortisone treatment
      and lipoteichoic acid (LTA) exposure, interleukin 6 (IL-6) and IL-1beta plasma
      levels, and blood counts were determined following sham operation or CLP using
      another n = 5 mice/group. Statistical analysis was performed using analysis of
      variance/Bonferroni. RESULTS: TLR2 mice exhibited a lack of suppression and an
      attenuated increase in endogenous corticosterone production following
      hydrocortisone or LTA treatment, respectively. After CLP, TLR2 mice exhibited an
      uncompromised adrenal stress response, higher IL-6 levels, and increased survival
      compared with WT controls (75 vs. 35%; P < 0.05). Hydrocortisone therapy of TLR2
      mice completely abolished this advantage (decrease in survival to 45%, P < 0.05
      vs. vehicle-treated TLR2 mice) and was associated with decreased IL-1beta plasma
      concentrations. CONCLUSIONS: Toll-like receptor 2 deficiency is associated with
      an uncompromised adrenal stress response and increased survival rates during
      polymicrobial sepsis. Hydrocortisone treatment increases mortality of septic TLR2
      mice, suggesting that hydrocortisone therapy might be harmful for individuals
      with functional TLR2 polymorphisms.

PMID- 24089005
TI  - A novel trauma model: naturally occurring canine trauma.
AB  - In human trauma patients, most deaths result from hemorrhage and brain injury,
      whereas late deaths, although rare, are the result of multiple organ failure and
      sepsis. A variety of experimental animal models have been developed to
      investigate the pathophysiology of traumatic injury and evaluate novel
      interventions. Similar to other experimental models, these trauma models cannot
      recapitulate conditions of naturally occurring trauma, and therefore therapeutic
      interventions based on these models are often ineffective. Pet dogs with
      naturally occurring traumatic injury represent a promising translational model
      for human trauma that could be used to assess novel therapies. The purpose of
      this article was to review the naturally occurring canine trauma literature to
      highlight the similarities between canine and human trauma. The American College
      of Veterinary Emergency and Critical Care Veterinary Committee on Trauma has
      initiated the establishment of a national network of veterinary trauma centers to
      enhance uniform delivery of care to canine trauma patients. In addition, the
      Spontaneous Trauma in Animals Team, a multidisciplinary, multicenter group of
      researchers has created a clinical research infrastructure for carrying out large
      scale clinical trials in canine trauma patients. Moving forward, these national
      resources can be utilized to facilitate multicenter prospective studies of canine
      trauma to evaluate therapies and interventions that have shown promise in
      experimental animal models, thus closing the critical gap in the translation of
      knowledge from experimental models to humans and increasing the likelihood of
      success in phases 1 and 2 human clinical trials. 

PMID- 24089004
TI  - Adenosine receptor antagonists effect on plasma-enhanced killing.
AB  - Previous studies demonstrated that naive plasma has inherent capabilities to
      enhance bacterial opsonization and phagocyte killing, but not all plasma is
      equally effective. This raised the question of whether plasma constituents other
      than opsonins may play a role. Adenosine receptor antagonists have been shown to
      modulate cytokine response and survival in mice after a bacterial challenge. We
      investigated whether selective adenosine receptor blockade would influence the
      ability of naive plasma to effectively control bacterial growth. Colonic bacteria
      and thioglycollate-elicited peritoneal macrophages and neutrophils were obtained
      from naive mice. Stock murine plasma from naive was purchased and categorized as
      having high plasma-enhanced bacterial killing capacity using our previously
      described methods. Bacteria and plasma were incubated to allow for opsonization
      and then added to macrophages previously exposed to selected adenosine receptor
      antagonists: ZM 241385: A2A, MRS1754: A2B, DPCPX: A1, and MRS1220: A3. The final
      mixture was plated on blood agar plates in aerobic and anaerobic conditions and
      bacterial colony-forming units quantified after 24 h. This study demonstrated
      that exogenous adenosine was able to significantly decrease phagocyte killing of
      cecal bacteria. Blocking adenosine receptors with selective antagonists altered
      the bacterial killing capacity of plasma. Selectively blocking the A1, A2A, or
      A2B receptors proved most beneficial at reversing the effect of adenosine.
      Consistent with previous work, only macrophage killing of bacteria could be
      modulated by adenosine receptor blockade because neutrophils were unaffected.
      These data demonstrate that adenosine decreases macrophage killing of enteric
      bacteria and that this effect is mediated through the adenosine receptors. 

PMID- 24089006
TI  - The Trauma Hemostasis and Oxygenation Research Network's Remote Damage Control
      Resuscitation Symposium.
AB  - This year, the Trauma Hemostasis and Oxygenation Research Network had its third
      annual conference from June 17 to 19 at the Solstrand Hotel, near Bergen, Norway.
      It was sponsored and organized by the Norwegian Naval Special Operation Commando
      together with the Norwegian Air Ambulance Foundation. The Trauma Hemostasis and
      Oxygenation Research Network is composed of more than 150 members from 16
      countries who all have a common interest in the prevention and treatment of
      traumatic hemorrhagic shock. The network is multidisciplinary to include members
      from both the military and civilian medical community representing areas of
      surgery, critical care, emergency medicine, transfusion medicine, anesthesiology,
      hematology, and basic science.

PMID- 24089007
TI  - Diagnostic potential of endotoxin scattering photometry for sepsis and septic
      shock.
AB  - Endotoxin scattering photometry (ESP) is a novel Limulus amebocyte lysate (LAL)
      assay that uses a laser light-scattering particle-counting method. In the present
      study, we compared ESP, standard turbidimetric LAL assay, and procalcitonin assay
      for the evaluation of sepsis after emergency gastrointestinal surgery. A total of
      174 samples were collected from 40 adult patients undergoing emergency
      gastrointestinal surgery and 10 patients with colorectal cancer undergoing
      elective surgery as nonseptic controls. Plasma endotoxin levels were measured
      with ESP and turbidimetric LAL assay, and plasma procalcitonin levels were
      assessed with a standard procalcitonin assay. Plasma endotoxin and procalcitonin
      levels increased corresponding to the degree of sepsis. Endotoxin scattering
      photometry significantly discriminated between patients with or without septic
      shock: sensitivity, 81.1%; specificity, 76.6%; positive predictive value, 48.4%;
      negative predictive value, 93.8%; and accuracy, 77.6%. The area under the
      receiver operating characteristic curve for septic shock with the ESP assay
      (endotoxin cutoff value, 23.8 pg/mL) was 0.8532 +/- 0.0301 (95% confidence
      interval, 0.7841-0.9030; P < 0.0001). The predictive power of ESP was superior to
      that of turbidimetric assay (difference, 0.1965 +/- 0.0588; 95% confidence
      interval, 0.0812-0.3117; P = 0.0008). There was no significant difference in
      predictive power between ESP and procalcitonin assay. Endotoxin scattering
      photometry also discriminated between patients with and without sepsis. Area
      under the receiver operating characteristic curve analysis showed that ESP had
      the best predictive power for diagnosing sepsis. In conclusion, compared with
      turbidimetric LAL assay, ESP more sensitively detected plasma endotoxin and
      significantly discriminated between sepsis and septic shock in patients
      undergoing gastrointestinal emergency surgery. 

PMID- 24089008
TI  - Impact of parenteral nutrition versus fasting on hepatic bile acid production and
      transport in a rabbit model of prolonged critical illness.
AB  - BACKGROUND: Cholestatic liver dysfunction frequently occurs during critical
      illness. Administration of parenteral nutrition (PN) is thought to aggravate
      this. Underlying mechanisms are not clear. METHODS: In a burn model of prolonged
      critical illness, rabbits were randomized to a nutritional strategy either
      accepting caloric deficits (fasted, n = 11) or covering caloric needs by PN (fed,
      n = 10). At baseline and after 7 days of critical illness, markers of
      hepatotoxicity, circulating bile acids, and the hepatobiliary transport system
      were studied. RESULTS: Fasted animals had lower circulating alanine
      aminotransferase/aspartate aminotransferase levels than did the fed animals at
      day 7. Compared with baseline values, fed animals displayed lower serum
      unconjugated cholic acid (CA) and deoxycholic acid (DCA) levels. Unconjugated DCA
      remained unaltered in fasted animals. Unconjugated lithocholic acid was increased
      comparably in all animals, whereas hyodeoxycholic acid was not altered. In
      contrast, fasting induced a shift from unconjugated CA and DCA to glyco-CA and
      glyco-DCA. Total bile acids did not correlate with the bile acid-producing enzyme
      CYP7A1, but with the basolateral efflux transporter MRP3. Fasting increased
      protein expression of the basolateral (MRP3) and the canalicular (BSEP)
      transporter, whereas the canalicular efflux pump MRP2 was suppressed. Gene
      expression levels of the nuclear receptor farnesoid X receptor were lower with
      fasting and correlated inversely with MRP3. The heterodimer partner of farnesoid
      X receptor, retinoid X receptor alpha, was increased with fasting and correlated
      positively with MRP3. CONCLUSIONS: During prolonged critical illness, withholding
      PN improved markers for hepatocyte injury and accentuated bile acid transport
      toward the blood. This suggests that the latter is an adaptive rather than a
      dysfunctional feedback to illness.

PMID- 24089009
TI  - High-mobility group box 1 mediates persistent splenocyte priming in sepsis
      survivors: evidence from a murine model.
AB  - Severe sepsis is a life-threatening complication of infection and injury
      affecting more than 700,000 people in the United States each year. Two thirds of
      patients with severe sepsis will survive to be discharged. Survivors have high
      incidence of cognitive impairment, immune dysregulation, functional impairments
      with marked disability, and 5-year mortality rates of 82%. High-mobility group
      box 1 (HMGB1) is necessary and sufficient mediator of sepsis pathogenesis in
      experimental models of this syndrome. The spleen is a crucial organ in the immune
      response to severe infection, and splenocyte dysfunction occurs in sepsis
      survivors. We hypothesized that HMGB1 plays a key role in mediating the immune
      dysfunction of splenocytes in sepsis survivors. Mice that survived cecal ligation
      and puncture-induced sepsis develop persistent splenomegaly; furthermore,
      splenocytes derived from sepsis survivors had enhanced responses to
      lipopolysaccharide ex vivo. Administration of neutralizing anti-HMGB1 antibody to
      sepsis survivors attenuated development of splenomegaly and reversed splenocyte
      priming. Splenocytes exposed to HMGB1 and subsequently challenged with cognate
      ligands to Toll-like receptor 2 (TLR2,) TLR4, TLR9, and RAGE (receptor for
      advanced glycation end product) receptors had enhanced cytokine release as
      compared with splenocytes not previously exposed to HMGB1. Exposure of TLR2,
      TLR9, or RAGE splenocytes to HMGB1 enhanced responses to other TLR receptor
      ligands; in contrast, HMGB1 failed to prime TLR4 splenocytes. These findings
      indicate that exposure to HMGB1 enhances splenocyte responses to secondary
      inflammatory challenges, a priming effect dependent on TLR4, and that anti-HMGB1
      monoclonal antibody may be beneficial in sepsis survivors. 

PMID- 24089010
TI  - Radial to femoral arterial blood pressure differences in septic shock patients
      receiving high-dose norepinephrine therapy.
AB  - OBJECTIVES: The accuracy of arterial blood pressure (ABP) monitoring is crucial
      in treating septic shock patients. Clinically significant differences in central
      to peripheral ABP could develop into sepsis during vasopressor therapy. The aim
      of this study was to investigate the difference between radial (peripheral) and
      femoral (central) ABP in septic shock patients receiving high-dose norepinephrine
      (NE) therapy. METHODS AND RESULTS: This prospective observational study comparing
      simultaneous intra-arterial measurements of radial and femoral ABP was performed
      at a university-affiliated, tertiary referral center between October 2008 and
      March 2009. Patients with septic shock who needed continuous blood pressure
      monitoring and high-dose NE therapy 0.1 ug/kg per minute or greater to maintain
      mean arterial pressure (MAP) of 65 mmHg or greater were included. Statistical
      analysis was conducted using the Bland-Altman method for comparison of repeated
      measures. In total, 250 sets of systolic, mean, and diastolic femoral and radial
      ABP were recorded at baseline and after NE titration. Arterial blood pressure
      readings from the radial artery were underestimated compared with those from the
      femoral artery. Overall bias (mean difference between simultaneous measurements)
      between radial and femoral MAP was +4.9 mmHg; however, during high-dose NE
      therapy, the bias increased to +6.2 mmHg (95% limits of agreement: -6.0 to +18.3
      mmHg). Clinically significant radial-femoral MAP differences (MAP >=5 mmHg)
      occurred in up to 62.2% of patients with high-dose NE therapy. CONCLUSIONS:
      Radial artery pressure frequently underestimates central pressure in septic shock
      patients receiving high-dose NE therapy. Femoral arterial pressure monitoring may
      be more appropriate when high-dose NE therapy is administered.

PMID- 24089012
TI  - Psychosis within vs outside of major mood episodes: a key prognostic and
      diagnostic criterion.

PMID- 24089013
TI  - Serum 25-hydroxyvitamin D levels in Chinese children with autism spectrum
      disorders.
AB  - In recent years, increasing evidence has shown that children with autism spectrum
      disorders (ASDs) have lower levels of 25-hydroxyvitamin D [25(OH) D] relative to
      healthy controls. The purpose of this study was to evaluate the serum 25(OH) D
      levels in Chinese children with ASD. From January 2012 to December 2012,
      consecutive patients with ASD admitted to the Department of Neurology were
      identified. Clinical information was collected. Serum levels of 25(OH) D were
      measured at baseline. ASD severity was assessed at admission using the Childhood
      Autism Rating Scale total score. The results indicated that the mean serum 25(OH)
      D levels were significantly lower in autistic children as compared with normal
      cases (P=0.002). There was a significant negative relationship between
      circulating serum 25(OH) D levels and the severity of autism evaluated according
      to Childhood Autism Rating Scale Scores (P=0.000), after adjustment for the
      possible covariates such as age, sex, BMI, serum levels of calcium, phosphate,
      and magnesium, and seasons. After adjusting for all other possible covariates,
      25(OH) D levels that remained can be seen as an independent predictor of ASD with
      an adjusted odds ratio of 1.23 (95% confidence interval, 1.10-1.37). These
      results indicate that lower 25(OH) D levels may be independently associated with
      severity of ASD among Chinese patients, and lower serum 25(OH) D levels could be
      considered as an independent risk factor for ASD. 

PMID- 24089011
TI  - Temporal metabolic profiling of plasma during endotoxemia in humans.
AB  - Endotoxemia induced by the administration of low-dose lipopolysaccharide (LPS) to
      healthy human volunteers is a well-established experimental protocol and has
      served as a reproducible platform for investigating the responses to systemic
      inflammation. Because metabolic composition of a tissue or body fluid is uniquely
      altered by stimuli and provides information about the dominant regulatory
      mechanisms at various cellular processes, understanding the global metabolic
      response to systemic inflammation constitutes a major part in this investigation
      complementing the studies undertaken so far in both clinical and systems biology
      fields. This article communicates the first proof-of-principle metabonomic
      analysis, which comprised global biochemical profiles in human plasma samples
      from healthy subjects given intravenous endotoxin at 2 ng/kg. Concentrations of a
      total of 366 plasma biochemicals were determined in archived blood samples
      collected from 15 endotoxin-treated subjects at five time points within 24 h
      after treatment and compared with control samples collected from four saline
      treated subjects. Principal component analysis within this data set determined
      the sixth hour as a critical time point separating development and recovery
      phases of the LPS-induced metabolic changes. Consensus clustering of the
      differential metabolites identified two distinct subsets of metabolites that
      displayed common coherent profiles with opposing directionality. The first group
      of metabolites, which were mostly associated with pathways related to lipid
      metabolism, was upregulated within the first 6 h and downregulated by the 24th
      hour following LPS administration. The second group of metabolites, in contrast,
      was first downregulated until the sixth hour, then upregulated. Metabolites in
      this group were predominantly amino acids or their derivatives. In summary,
      nontargeted biochemical profiling and unsupervised multivariate analyses
      highlighted the prominent roles of lipid and protein metabolism in regulating the
      response to systemic inflammation while also revealing their dynamics in opposite
      directions. 

PMID- 24089014
TI  - Role of central arginine vasopressin receptors in the analgesic effect of CDP
      choline on acute and neuropathic pain.
AB  - Recent studies have demonstrated that arginine vasopressin (AVP) plays a crucial
      role in pain modulation. In addition, our previous studies have proven that
      centrally administered cytidine-5'-diphosphate-choline (CDP-choline; citicoline)
      elicits an analgesic effect in different pain models in rats. Given that CDP
      choline enhances central and peripheral vasopressin levels, the present study was
      designed to investigate the role of central AVP receptors in the analgesic effect
      of CDP-choline in acute and chronic constriction injury-induced neuropathic pain
      models. For this purpose, rats were pretreated intracerebroventricularly with the
      AVP V1 or AVP V2 receptor antagonist 15 min before intracerebroventricular
      injection of CDP-choline or saline, and pain threshold was determined using the
      Randall-Selitto test. AVP V1 and AVP V2 receptor antagonist blocked the CDP
      choline-induced analgesic effect either in acute or neuropathic models of pain in
      rats. These results suggest, for the first time, that central AVP receptors are
      involved in the CDP-choline-elicited analgesic effect. 

PMID- 24089015
TI  - Characterization of human pluripotent stem cells.
AB  - Human pluripotent stem cells (PSCs), whether embryonic stem cells or induced
      PSCs, offer enormous opportunities for regenerative medicine and other biomedical
      applications once we have developed the ability to harness their capacity for
      extensive differentiation. Central to this is our ability to identify and
      characterize such PSCs, but this is fraught with potential difficulties that
      arise from a tension between functional definitions of pluripotency and the more
      convenient use of 'markers', a problem exacerbated by ethical issues, our lack of
      knowledge of early human embryonic development, and differences from the mouse
      paradigm. 

PMID- 24089016
TI  - Specific de-SUMOylation triggered by acquisition of spatial learning is related
      to epigenetic changes in the rat hippocampus.
AB  - Histone acetyltransferase activity by transcriptional cofactors such as CREB
      binding protein (CBP) and post-translational modifications by small ubiquitin
      like modifier-1 (SUMO-1) have shown to be relevant for synaptic and neuronal
      activity. Here, we investigate whether SUMOylation of CBP plays a role in spatial
      learning. We assessed protein levels of CBP/p300, SUMO-1, and CBP SUMOylation in
      the hippocampi of rats trained on the Morris water maze task. Furthermore, we
      evaluated the post-translational modifications at Zif268, BDNF, and Arc/Arg3.1
      promoters using chromatin immunoprecipitation with anti-Acetyl-Histone H3-Lys14
      (H3K14Ac) and SUMO-1. We found that CBP/p300 protein expression is unchanged in
      animals trained for 7 days. However, H3K14Ac-specific histone acetyltransferase
      activity showed specific hyperacetylation at promoters of Zif268 and BDNF-pI but
      not of Arc/Arg3.1 and BDNF-pIV. In naive animals, CBP is selectively SUMOylated
      and the Arc/Arg3.1 promoter is differentially occupied by SUMO-1, although SUMO-1
      levels are unchanged. These results suggest a specific negative regulation by
      SUMO-1 on CBP function and its effect on epigenetic changes triggered by spatial
      learning and memory processes. 

PMID- 24089017
TI  - Neuronal correlates of mental rotation performance in children with developmental
      dyslexia.
AB  - People with developmental dyslexia have been shown to have both behavioral and
      physiological differences when compared with healthy individuals, specifically
      when looking at the parietal cortex. Reading and writing deficits are well
      documented, but other cognitive deficits in dyslexia are not as well known. To
      investigate spatial deficits in children with developmental dyslexia we used a
      mental rotation test with three types of stimuli (letters, animals, and objects
      that look like letters) while simultaneously recording electroencephalographs.
      Behaviorally, it was found that dyslexic children took more time than nondyslexic
      children to solve the 'letter' and 'object' stimuli and that the dyslexic
      children had a slower mental rotation speed when solving 'letter' stimuli. The
      electroencephalographic data demonstrated more negative amplitude modulations for
      the dyslexic group in the left hemisphere at the time epochs: 200-300, 600-700,
      700-800, 800-900, and 900-1000 ms and in the right hemisphere for the time epoch
      600-700 and 900-100 ms. In addition, hemispheric group differences were found on
      the basis of stimuli for the time epoch 600-700 ms in which the processing of
      letters was lateralized to the left hemisphere for both groups, but the object
      stimuli was lateralized to the left for nondyslexic and to the right for dyslexic
      children. These differences support the idea that the behavioral differences
      found between dyslexic and nondyslexic children may be because of both
      differences in the early processing of the stimuli and perhaps in the mental
      rotation itself. 

PMID- 24089018
TI  - Is lipoprotein-associated phospholipase A2 activity correlated with fibrous-cap
      thickness and plaque volume in patients with acute coronary syndrome?
AB  - BACKGROUND: Lipoprotein-associated phospholipase A2 (Lp-PLA2) is a specific
      biomarker specific for vascular inflammation. Inflammation has a significant
      association with plaque progression. The fibrous-cap thickness (FCT) is one of
      the major determinants of plaque vulnerability in atherosclerotic plaques.
      However, data on the relationship between Lp-PLA2 activity and FCT in lipid
      plaque are limited. This study aimed to evaluate the in-vivo association between
      changes in Lp-PLA2 activity and FCT and plaque volume in patients with acute
      coronary syndrome (ACS). PATIENTS AND METHODS: Twenty-four consecutive patients
      with ACS were enrolled between May 2010 and May 2012. The plaque volume and FCT
      of nonculprit lipid-rich plaques were assessed by intravascular ultrasound and
      optical coherence tomography, respectively, at baseline and after 12 months. Lp
      PLA2 activity was determined using the colorimetric assay kit. RESULTS: During
      the 12 months of observation, FCT increased significantly from baseline to follow
      up, with a mean percent change of 74.4+/-46.8%. A significant correlation was
      observed between changes in Lp-PLA2 activity and changes in FCT (r=-0.56,
      P=0.006). Changes in plaque volume were also correlated significantly with
      changes in Lp-PLA2 activity during the study period (r=0.52, P=0.01). CONCLUSION:
      Significant associations between serial changes in Lp-PLA2 activity and changes
      in FCT and plaque volume were observed in patients with ACS.

PMID- 24089019
TI  - A chimeric RNA characteristic of rhabdomyosarcoma in normal myogenesis process.
AB  - Gene fusions and their chimeric products are common features of neoplasia. Given
      that many cancers arise by the dysregulated recapitulation of processes in normal
      development, we hypothesized that comparable chimeric gene products may exist in
      normal cells. Here, we show that a chimeric RNA, PAX3-FOXO1, identical to that
      found in alveolar rhabdomyosarcoma, is transiently present in cells undergoing
      differentiation from pluripotent cells into skeletal muscle. Unlike cells of
      rhabdomyosarcoma, these cells do not seem to harbor the t(2;13) chromosomal
      translocation. Importantly, both PAX3-FOXO1 RNA and protein could be detected in
      the samples of normal fetal muscle. Overexpression of the chimera led to
      continuous expression of MYOD and MYOG-two myogenic markers that are
      overexpressed in rhabdomyosarcoma cells. Our results are consistent with a
      developmental role of a specific chimeric RNA generated in normal cells without
      the corresponding chromosomal rearrangement at the DNA level seen in neoplastic
      cells presumably of the same lineage. SIGNIFICANCE: A chimeric fusion RNA, PAX3
      FOXO1, associated with alveolar rhabdomyosarcoma, is also present in normal non
      cancer cells and tissues. Its transient expression nature and the absence of
      t(2;13) chromosomal translocation are consistent with a posttranscriptional
      mechanism. When constantly expressed, PAX3-FOXO1 interfered with the muscle
      differentiation process, which presumably contributes to tumorigenesis.

PMID- 24089020
TI  - Ferroelectric control of a Mott insulator.
AB  - The electric field control of functional properties is an important goal in oxide
      based electronics. To endow devices with memory, ferroelectric gating is
      interesting, but usually weak compared to volatile electrolyte gating. Here, we
      report a very large ferroelectric field-effect in perovskite heterostructures
      combining the Mott insulator CaMnO3 and the ferroelectric BiFeO3 in its
      "supertetragonal" phase. Upon polarization reversal of the BiFeO3 gate, the
      CaMnO3 channel resistance shows a fourfold variation around room temperature, and
      a tenfold change at ~200 K. This is accompanied by a carrier density modulation
      exceeding one order of magnitude. We have analyzed the results for various CaMnO3
      thicknesses and explain them by the electrostatic doping of the CaMnO3 layer and
      the presence of a fixed dipole at the CaMnO3/BiFeO3 interface. Our results
      suggest the relevance of ferroelectric gates to control orbital- or spin-ordered
      phases, ubiquitous in Mott systems, and pave the way toward efficient Mott
      tronics devices. 

PMID- 24089021
TI  - Diffusion-weighted magnetic resonance imaging of the pancreas: diagnostic benefit
      from an intravoxel incoherent motion model-based 3 b-value analysis.
AB  - OBJECTIVES: The objective of this study was to evaluate the diagnostic benefit of
      an intravoxel incoherent motion (IVIM) model-based characterization of pancreatic
      masses from diffusion-weighted imaging (DWI) with 3 b values. MATERIALS AND
      METHODS: This retrospective study had an approval from the institutional review
      board, and informed patient consent was waived. The 1.5-T DWI data of 42 patients
      with or without pancreatic disease, acquired by a respiratory-gated spin-echo
      echo-planar imaging sequence with 3 b values (0, 50, 800 s/mm2), were
      retrospectively analyzed. The IVIM-related parameters D', which is the apparent
      diffusion coefficient [ADC(50,800)], and f', as well as ADC(0,50), and
      conventional ADC(0,800) were calculated voxelwise. Regions of interest were
      analyzed in pancreatic adenocarcinomas (CAs, n = 12), neuroendocrine pancreatic
      tumors (NETs, n = 9), and chronic pancreatitis (CPs, n = 11), not affected tissue
      of each pathologic group, and in the head, body, and tail of the healthy pancreas
      (n = 10). RESULTS: By ADC(0,800) and D', CAs could hardly be distinguished from
      neuroendocrine pancreatic tumors and chronic pancreatitis. However, CAs revealed
      very low ADC(0,50) and f' values, which differed significantly from all other
      groups. In the healthy pancreas, ADC(0,800) and D' values were significantly
      higher for the head than for the body and tail, but no significant differences
      were found for ADC(0,50) and f'. CONCLUSIONS: The determination of IVIM-based
      microcirculation-sensitive parameter maps from DWI with 3 b values significantly
      improved the discrimination of CAs from NETs, CPs, and the healthy tissue.

PMID- 24089022
TI  - Seven-tesla magnetic resonance imaging accurately quantifies intratumoral uptake
      of therapeutic nanoparticles in the McA rat model of hepatocellular carcinoma:
      preclinical study in a rodent model.
AB  - OBJECTIVES: After inducing McA tumors in Sprague-Dawley rats (McA-SD), the
      following hypotheses were tested: first, that hypervascular McA tumors grown in
      Sprague-Dawley rats provide a suitable platform to investigate drug delivery; and
      second, that high-field MRI can be used to measure intratumoral uptake of DOX
      SPIOs. MATERIALS AND METHODS: McA cells were implanted into the livers of 18
      Sprague-Dawley rats. In successfully inoculated animals, 220-MUL DOX-SPIOs were
      delivered to tumors via the intravenous or intra-arterial route. Pretreatment and
      posttreatment T2*-weighted images were obtained using 7-T MRI, and change in R2*
      value (DeltaR2*) was obtained from mean signal intensities of tumors in these
      images. Tumor iron concentration ([Fe]), an indicator of DOX-SPIO uptake, was
      measured using mass spectroscopy. The primary outcome variable was the Pearson
      correlation between DeltaR2* and [Fe]. RESULTS: Tumors grew successfully in 13 of
      the 18 animals (72%). Mean (SD) maximum tumor diameter was 0.83 (0.25) cm. The
      results of phantom studies revealed a strong positive correlation between
      DeltaR2* and [Fe], with r = 0.98 (P < 0.01). The results of in vivo drug uptake
      studies demonstrated a positive correlation between DeltaR2* and [Fe], with r =
      0.72 (P = 0.0004). CONCLUSIONS: The McA tumors grown in the Sprague-Dawley rats
      demonstrated uptake of nanoparticle-based therapeutic agents. Magnetic resonance
      imaging quantification of intratumoral uptake strongly correlated with iron
      concentrations in pathological specimens, suggesting that MRI may be used to
      quantify uptake of iron-oxide nanotherapeutics.

PMID- 24089023
TI  - The importance of early treatment for the prognosis of rheumatoid arthritis.
AB  - Chronic synovial inflammation in rheumatoid arthritis (RA) leads to progressive
      damage to articular cartilage and bone, ultimately resulting in disability.
      Therefore, control of the articular inflammation is of great importance to
      prevent joint damage. A variety of disease-modifying antirheumatic drugs (DMARDs)
      are available for RA patients. Conventional synthetic DMARDs, and in particular
      biological DMARDs, have been shown to effectively inhibit joint destruction in
      RA. Longitudinal assessments of radiographic changes in patients with RA in
      clinical trials and in large patient registries have clearly shown that delays in
      the initiation of DMARD therapy results in significantly increased progression of
      joint damage. Patients started early on DMARDs had significantly lower
      radiographic damage progression than patients initiating DMARD treatment later.
      These effects were maintained for several years, suggesting that early in the
      development of RA a therapeutic window of opportunity exists in which DMARD
      therapy decisively influences the long-term prognosis. Therefore, to improve the
      clinical outcome of RA, our efforts should be directed towards diagnosing RA
      earlier and introducing DMARD therapy immediately after the diagnosis has been
      made. 

PMID- 24089024
TI  - 2D layered insulator hexagonal boron nitride enabled surface passivation in dye
      sensitized solar cells.
AB  - A two-dimensional layered insulator, hexagonal boron nitride (h-BN), is
      demonstrated as a new class of surface passivation materials in dye-sensitized
      solar cells (DSSCs) to reduce interfacial carrier recombination. We observe ~57%
      enhancement in the photo-conversion efficiency of the DSSC utilizing h-BN coated
      semiconductor TiO2 as compared with the device without surface passivation. The h
      BN coated TiO2 is characterized by Raman spectroscopy to confirm the presence of
      highly crystalline, mixed monolayer/few-layer h-BN nanoflakes on the surface of
      TiO2. The passivation helps to minimize electron-hole recombination at the
      TiO2/dye/electrolyte interfaces. The DSSC with h-BN passivation exhibits
      significantly lower dark saturation current in the low forward bias region and
      higher saturation in the high forward bias region, respectively, suggesting that
      the interface quality is largely improved without impeding carrier transport at
      the material interface. The experimental results reveal that the emerging 2D
      layered insulator could be used for effective surface passivation in solar cell
      applications attributed to desirable material features such as high crystallinity
      and self-terminated/dangling-bond-free atomic planes as compared with high-k thin
      film dielectrics.

PMID- 24089025
TI  - One step synthesis of benzoxazepine derivatives via a PPh(3) catalyzed aza-MBH
      domino reaction between salicyl N-tosylimines and allenoates.
AB  - PPh3-Catalyzed aza-MBH domino reaction of salicyl N-tosylimines with gamma-CH3
      substituted allenoates is reported. Readily available imines and allenoates are
      converted to benzoxazepine derivatives in one step. Wherein, functionalization of
      C-H bonds of gamma-substituted allenoate has been developed in this domino
      process. 

PMID- 24089027
TI  - Skin conductance as a marker of pain in infants of different gestational age.
AB  - AIMS: To assess the use of skin conductance as an objective measure of pain in
      infants of different gestational age. A second aim was to investigate the
      relationship between skin conductivity and selected physiological and behavioural
      variables (oxygen saturation, heart rate and behavioural state). METHODS: Infants
      were divided according to gestational age into the following 3 groups; group A:
      25+0-31+6 weeks (13 infants), group B: 32+0-35+6 weeks (25 infants), group C:
      36+0-41+6 weeks (19 infants). The pain stimulus was blood sampling. RESULTS: The
      most sensitive parameter for describing changes in skin conductance related to
      pain was peak per second. No other parameter correlated with the physiological
      variables chosen. The results showed that the inability to determine basal skin
      conductance is a crucial disadvantage to practical application. The lack of
      correlation between conductance parameters and gestational age is surprising.
      CONCLUSION: We conclude that the Peak per Second is the best parameter for
      evaluating skin conductance in infants and it is not influenced by gestational
      age. Peaks per Second correlate only with Prechtl's Scale of behavioural state
      and not with the physiological parameters chosen.

PMID- 24089026
TI  - Supine lithotomy versus prone position in minimally invasive percutaneous
      nephrolithotomy for upper urinary tract calculi.
AB  - OBJECTIVE: To compare operative time, safety and effectiveness of minimally
      invasive percutaneous nephrolithotomy (MPCNL) in the supine lithotomy versus
      prone position. METHODS: Between January 2008 and December 2010, a total of 109
      consecutive patients with upper urinary tract calculi were enrolled and randomly
      divided into group A (53 patients, supine lithotomy position) and group B (56
      patients, prone position). The MPCNL procedures were performed under the guidance
      of real-time grayscale ultrasound system. The preoperative characteristics,
      intraoperative and postoperative parameters were analyzed and compared. RESULTS:
      All patients were successfully operated. There was no significant difference
      between the two groups in stone-free rate (group A 90.1 vs. group B 87.5%, p =
      0.45), mean blood loss, number of access tracts, calyx puncture, mean hospital
      stay (group A 6 +/- 1.1 vs. group B 6 +/- 1.5 days, p = 0.38) and complications.
      But the operative time was significantly shortened in supine lithotomy position
      (group A 56 +/- 15 vs. group B 86 +/- 23 min, p < 0.001). CONCLUSIONS: The
      effectiveness and safety of the supine lithotomy position for MPCNL were similar
      to the prone position. However, the supine lithotomy position has an important
      advantage of reducing the operative time. The supine lithotomy position could be
      a good choice to perform MPCNL.

PMID- 24089028
TI  - Hypoxia-inducible factor-1alpha polymorphisms link to coronary artery collateral
      development and clinical presentation of coronary artery disease.
AB  - AIMS: This study aimed to investigate the association of Hypoxia-inducible factor
      1alpha (HIF-1alpha) C1772T and G1790A single nucleotide polymorphisms (SNPs)
      with: incidence, clinical type, severity of coronary atherosclerosis and coronary
      collaterals of coronary artery disease (CAD). METHODS: The clinical data and
      genomic DNA were gathered in 958 subjects, including 560 controls and 398
      patients with CAD. CAD was confirmed with coronary angiography (CAG). The
      genotypes for two SNPs were determined by high resolution melting after PCR
      amplification. RESULTS: Neither the HIF-1alpha C1772T nor the G1790A genotype was
      significantly associated with CAD and, no gene-gene or gene-environmental
      interactions were identified. However, both HIF-1alpha C1772T and G1790A (P<0.05)
      alleles were associated with clinical type and formation of coronary collaterals
      (P<0.05). Patients carrying genotype CT (P=0.019, OR=4.905,91, 95% CI: 1.355
      17.761) and GA (P=0.026, OR=3.052, 95% CI: 1.180-7.892) had significantly higher
      stable angina pectoris (SAP) than unstable angina pectoris (UAP) and acute
      myocardial infarction (AMI). The presence of HIF-1 genotype CT (P=0.016,
      OR=13.373, 95% CI: 15.468-32.709) and GA (P=0.001, OR=19.741, 95% CI: 8.125
      47.966) predicted lower collateral formation and severity of CAD secondary to the
      absence of collaterals (r=0.242, P<0.001). CONCLUSIONS: We conclude that
      functional polymorphisms in the HIF-1alpha gene do not modify CAD risk but they
      are associated with the formation of coronary collaterals and clinical
      presentation of CAD.

PMID- 24089030
TI  - Coverage of atypical pathogens for hospitalised patients with community-acquired
      pneumonia is not guided by clinical parameters.
AB  - BACKGROUND: Although most experts recommend empirical antibiotic treatment,
      covering also atypical bacteria, for patients admitted to an intensive care unit
      (ICU), the data are not clear for patients admitted to a general ward. European
      guidelines recommend starting empirical treatment with a beta-lactam antibiotic
      with or without a macrolide, but the with/without is not clarified. We
      investigated whether the use of antibiotic coverage for atypical pathogens was
      guided by clinical parameters. METHODS: We retrospectively analysed 300 patients
      hospitalised with community-acquired pneumonia. Four parameters for possible
      atypical pneumonia (age <55 years, abdominal symptoms, sodium <130 mmol/l,
      immunosuppression) and three for pneumonia severity (pneumonia severity index
      [PSI], ICU admission, pO2 <8 kPa (60 mm Hg) or O2 saturation <90%) were defined
      and correlated with the probability of coverage for atypical pathogens.
      Correlations were calculated using the chi-square test for 2 x 2 tables. RESULTS:
      Patients younger than 55 years significantly more likely to receive coverage for
      atypical pathogens than older patients (odds ratio [OR] 2.68; 95% confidence
      interval [CI] 1.3-5.5, p = 0.009). In patients with a PSI >III the proportion
      receiving coverage for atypical bacteria was even smaller than in patients with
      less severe pneumonia (OR 0.77; 95% CI 0.60-0.99, p = 0.03), but no difference
      was found for PSI >IV compared with PSI <=IV (OR = 1.03; 95% CI 0.61-1.74, p =
      0.9). The other clinical parameters had no effect on antibiotic coverage: ICU
      admission (OR =1.39; 95% CI 0.87-2.4, p = 0.15); pO2 >8 kPa or O2-Saturation >90%
      (OR 1.36; 95% CI 0.85-2.17, p = 0.19); abdominal symptoms (OR 1.06; 95% CI 0.51
      2.25, p = 0.88); sodium <130 mmol/l (OR 0.63; 95% CI 0.29-1.36, p = 0.2) or
      immunosuppression (OR 1.007; 95% CI 0.462-44, p = 1). There was also no
      correlation between the number of clinical parameters present and the coverage of
      atypical pathogens (r = 0.48). Mortality was no different between patients in
      whom atypical pathogens were covered compared with those with beta-lactam therapy
      alone (OR 1.2; 95% CI 0.66-2.25, p = 0.43). CONCLUSION: Physicians have
      difficulties deciding when to cover atypical pathogens in hospitalised patients
      with community-acquired pneumonia. Guidelines should clarify under what
      circumstances combination therapy is warranted.

PMID- 24089031
TI  - Is the 2,3-carbon-carbon bond of indole really inert to oxidative cleavage by
      Oxone?--synthesis of isatoic anhydrides from indoles.
AB  - A recent report has indicated that the oxidizing agent Oxone does not possess the
      ability to cleave the 2,3-carbon-carbon bond of indole. Work in our laboratory
      shows that this is not the case. Indole and a variety of aryl ring substituted
      derivatives readily react to form synthetically important isatoic anhydrides. 

PMID- 24089029
TI  - The mutational landscape of phosphorylation signaling in cancer.
AB  - Somatic mutations in cancer genomes include drivers that provide selective
      advantages to tumor cells and passengers present due to genome instability.
      Discovery of pan-cancer drivers will help characterize biological systems
      important in multiple cancers and lead to development of better therapies. Driver
      genes are most often identified by their recurrent mutations across tumor
      samples. However, some mutations are more important for protein function than
      others. Thus considering the location of mutations with respect to functional
      protein sites can predict their mechanisms of action and improve the sensitivity
      of driver gene detection. Protein phosphorylation is a post-translational
      modification central to cancer biology and treatment, and frequently altered by
      driver mutations. Here we used our ActiveDriver method to analyze known
      phosphorylation sites mutated by single nucleotide variants (SNVs) in The Cancer
      Genome Atlas Research Network (TCGA) pan-cancer dataset of 3,185 genomes and 12
      cancer types. Phosphorylation-related SNVs (pSNVs) occur in ~90% of tumors, show
      increased conservation and functional mutation impact compared to other protein
      coding mutations, and are enriched in cancer genes and pathways. Gene-centric
      analysis found 150 known and candidate cancer genes with significant pSNV
      recurrence. Using a novel computational method, we predict that 29% of these
      mutations directly abolish phosphorylation or modify kinase target sites to
      rewire signaling pathways. This analysis shows that incorporation of information
      about protein signaling sites will improve computational pipelines for variant
      function prediction. 

PMID- 24089034
TI  - The dream: Henri Rousseau.

PMID- 24089036
TI  - High prevalence and low fecundity of mental disorders may reflect recessive
      effects.

PMID- 24089037
TI  - Fertility rates in patients with mood disorder in Sweden and Sardinia.

PMID- 24089038
TI  - Progressive changes in chromatin structure and DNA damage response signals in
      bone marrow and peripheral blood during myelomagenesis.
AB  - The molecular pathways implicated in multiple myeloma (MM) development are rather
      unknown. We studied epigenetic and DNA damage response (DDR) signals at selected
      model loci (N-ras, p53, d-globin) in bone marrow plasma cells and peripheral
      blood mononuclear cells (PBMCs) from patients with monoclonal gammopathy of
      undetermined significance (MGUS; n=20), smoldering/asymptomatic MM (SMM; n=29)
      and MM (n=18), as well as in healthy control-derived PBMCs (n=20). In both
      tissues analyzed, a progressive, significant increase in the looseness of local
      chromatin structure, gene expression levels and DNA repair efficiency from MGUS
      to SMM and finally to MM was observed (all P<0.002). Following ex vivo treatment
      with melphalan, a gradual suppression of the apoptotic pathway occurred in
      samples collected at different stages of myelomagenesis, with the severity and
      duration of the inhibition of RNA synthesis, p53 phosphorylation at serine15 and
      induction of apoptosis being higher in MGUS than SMM and lowest in MM patients
      (all P<0.0103). Interestingly, for all endpoints analyzed, a strong correlation
      between plasma cells and corresponding PBMCs was observed (all P<0.0003). We
      conclude that progressive changes in chromatin structure, transcriptional
      activity and DDR pathways during myelomagenesis occur in malignant plasma cells
      and that these changes are also reflected in PBMCs. 

PMID- 24089039
TI  - Reasons for misuse of prescription medication among physicians undergoing
      monitoring by a physician health program.
AB  - OBJECTIVES: Substance-related impairment of physicians is a small but serious
      problem, with significant consequences for patient safety and public health. The
      purpose of this study was to identify reasons for prescription drug misuse among
      physicians referred to a physician health program for monitoring because of
      substance-related impairment, to develop better mechanisms for prevention and
      intervention. METHODS: A total of 55 physicians (94.5% male) who were being
      monitored by their State physician health program because of substance-related
      impairment participated in guided focus group discussions. Participation was
      anonymous. Discussions were transcribed from 9 separate focus groups, lasting 60
      to 90 minutes each. Qualitative analyses were conducted to examine themes.
      RESULTS: All participants were diagnosed with substance dependence, and 69.1% of
      them endorsed a history of misusing prescription drugs. Participants documented
      the following 5 primary reasons for prescription drug misuse: (1) to manage
      physical pain, (2) to manage emotional/psychiatric distress, (3) to manage
      stressful situations, (4) to serve recreational purposes, and (5) to avoid
      withdrawal symptoms. CONCLUSIONS: Our results emphasize the importance of self
      medication as a leading reason for misusing prescription medications, although
      recreational use was also an important factor. Prevention efforts targeting
      prescription drug misuse among physicians should be initiated during medical
      training, with continuing education requirements throughout the physicians'
      careers.

PMID- 24089041
TI  - Impact of 5-HTTLPR polymorphism on alexithymia in alcoholic patients after
      detoxification treatment.

PMID- 24089040
TI  - Characteristics of an outpatient treatment sample by primary substance of abuse.
AB  - OBJECTIVE: This study examines sociodemographic and clinical characteristics, as
      a function of primary substance of abuse, among clients approached, screened, and
      assessed for eligibility in a 10-site effectiveness trial of a Web-based
      psychosocial intervention for substance use disorders. Consistent with the design
      of effectiveness trials, eligibility criteria were broad and exclusion criteria
      minimal; thus, the recruited sample may be viewed as relatively representative of
      patients seeking treatment throughout the United States. METHODS: chi tests for
      categorical variables and F tests for continuous variables were used to analyze
      demographic, substance use, physical and mental health, and sexual risk data
      collected at screening and baseline; pairwise comparisons between primary
      substance subgroups for baseline data were conducted if the test statistic P
      value was 0.01 or less. RESULTS: Few participants expressed disinterest in the
      study at screening because of the computer-assisted intervention. A diverse
      sample of substance users completed baseline and were enrolled: 22.9% marijuana;
      21.7% opiates; 20.9% alcohol; 20.5% cocaine; and 13.9% stimulants users.
      Marijuana users demonstrated the greatest differences across primary substances:
      they were younger, less likely to be married or attend 12-step meetings, and more
      likely to be in treatment as a result of criminal justice involvement. All
      patients, even marijuana users, reported comparable rates of co-occurring mental
      health disorders and sexual risk and substantial rates of polysubstance use
      disorders. CONCLUSIONS: Primary substance of abuse may be a less important
      indicator of overall severity compared with co-occurring disorders and other
      factors common across treatment seekers, further demonstrating the need for
      integrated treatment services and care and comprehensive pretreatment assessment.

PMID- 24089043
TI  - Graphene-based hollow spheres as efficient electrocatalysts for oxygen reduction.
AB  - A facile and straightforward approach is developed for the construction of
      graphene-based hollow spheres. An electron rich sodium-ammonia solution is used
      to effectively restore the pi-conjugation of graphene. The hollow spheres exhibit
      excellent electrocatalytic activity towards oxygen reduction without catalyst
      deactivation. 

PMID- 24089045
TI  - The impact of body mass index on hospital stay and complications after spinal
      fusion.
AB  - BACKGROUND: Obesity is a dominant public health concern and risk factor for
      disability, with few studies examining its impact in spinal surgery. Patients
      with a higher body mass index (BMI) have lower functional status, increased pain,
      and worse physical condition than those with ideal weight. OBJECTIVE: To
      determine associations between BMI categories on adverse patient outcomes after
      long-segment spinal fusions. METHODS: Consecutive, open, elective fusions
      (interbody and/or posterolateral arthrodesis) of more than 5 levels from 2007 to
      2010 were retrospectively analyzed with follow-up of more than 1 year. Bivariate
      analyses examined outcome variables based on BMI categories. Linear regression
      analysis evaluated BMI, hospital stay, and complications at 1 and 2 years,
      controlling for confounders. Mean and median follow-up lengths were 2.1 and 2.0
      years, respectively. RESULTS: A total of 189 surgeries on 112 patients, with a
      mean age of 59.5 years and a mean BMI of 29.8 kg/m, were analyzed. Morbidly obese
      patients had longer hospitalizations, worse Oswestry Disability Index (ODI), and
      more complications at 1 and 2 years than ideal weight patients. Multivariate
      linear regression modeling revealed sex, cardiac medications, cerebrospinal fluid
      leak, and BMI category of ideal vs nonideal influenced hospitalization length.
      Multivariate analysis showed BMI greater than 30 kg/m, preoperative ODI, and
      pedicle subtraction osteotomy influenced all complications at 1 year. Mean
      complications at 2 years for the morbidly obese were 3 times more than those
      underweight and 8 times more than those with ideal weight. Controlling for age,
      sex, and length of stay, obese and morbidly obese patients had more complications
      at 2 years; morbidly obese patients had a worse 2-year ODI. CONCLUSION: BMI is an
      independent predictor of hospitalization length and all complications at 1 and 2
      years in patients receiving long-segment fusions.

PMID- 24089044
TI  - Feasibility of correction with instrumentation only in congenital scoliosis.
AB  - BACKGROUND: Although effective correction of deformity in congenital scoliosis
      can often be achieved with instrumentation only and without more invasive
      techniques such as hemivertebrectomy (HV), reports of the feasibility of
      correction with instrumentation only (IO) are lacking. OBJECTIVE: To compare the
      results of deformity correction using IO vs HV and to examine the feasibility of
      and indications for correction with IO in patients with congenital scoliosis.
      METHODS: Twenty-five patients underwent correction with either IO (n = 14) or HV
      (n = 11). The 2 patient groups were compared in terms of age at the time of
      surgery, preoperative magnitude and flexibility of the main curve, correction
      rates after surgery and at the final follow-up, surgery time, estimated blood
      loss, and complications. RESULTS: The 2 groups did not differ significantly in
      terms of average patient age or curve magnitude, but the correction with the IO
      group had greater preoperative curve flexibility (37.1%) than the HV group
      (21.0%). The correction rates immediately after surgery were high in both groups.
      The correction with IO group had a shorter mean operation time (308 minutes vs
      366 minutes) and less blood loss (540 mL vs 1547 mL) than the HV group.
      CONCLUSION: Satisfactory correction of congenital scoliosis can be obtained with
      IO if there is adequate flexibility in the main curve, thus avoiding the need for
      more invasive procedures such as HV.

PMID- 24089046
TI  - Ventriculoperitoneal shunt 30-day failure rate: a retrospective international
      cohort study.
AB  - BACKGROUND: With the need for transparency of surgical results, 30-day outcome
      measures have become increasingly important. Ventriculoperitoneal (VP) shunt
      failure is a substantial burden to patients and health care systems. OBJECTIVE:
      This study introduces the 30-day VP shunt failure rate as a possible barometer of
      surgical outcome and demonstrates its use in a national (United Kingdom [UK])
      study and makes comparison with 2 published randomized, controlled trials (RCT).
      METHODS: A cohort study of all (except 1) pediatric neurosurgical centers in the
      UK and Ireland. All new and revision VP shunt operations were recorded for 2008
      and 2009. Both newly placed and revised VP shunts were subject to Kaplan-Meier
      analysis, and 30-day failure rate was obtained. Data from 2 RCTs investigating
      new VP shunt technology were analyzed, and the 30-day failure rate was extracted
      for comparative purposes. RESULTS: The overall 30-day and 1-year failure rates
      for new shunts were 12.9% and 28.8%, respectively. The 30-day failure rate from 2
      RCTs was comparable (14% and 16%, respectively). The failure rate of the
      subsequent revision of those new shunts was 20.7% at 30 days and 40.4% at 1 year.
      According to these data, shunt survival appears to be better if performed by a
      consultant pediatric neurosurgeon for revision surgery only. CONCLUSION: VP shunt
      survival in the UK is comparable to the published multicenter data investigating
      shunt survival. The 30-day failure rate may represent a better barometer of
      surgical outcome and should be used as a separate outcome measure in the design
      of future trials.

PMID- 24089047
TI  - Outcomes after anterior or complete corpus callosotomy in children.
AB  - BACKGROUND: Corpus callosotomy (CC) is a valuable palliative surgical option for
      children with medically refractory epilepsy due to generalized or multifocal
      cortical seizure onset. OBJECTIVE: To investigate the extent of CC resulting in
      optimal seizure control in a pediatric patient population and to evaluate the
      modification of seizure profile after various CC approaches. METHODS: The records
      of 58 children (3-22 years of age at the time of surgery) with medically
      refractory epilepsy who underwent CC between 1995 and 2011 were retrospectively
      reviewed. RESULTS: Anterior two thirds callosotomy resulted in resolution of
      absence (P = .03) and astatic (P = .03) seizures, whereas anterior two thirds
      callosotomy followed by second-stage completion resulted in resolution of
      generalized tonic-clonic (GTC) (P = .03), astatic (P = .005), and myoclonic (P =
      .03) seizures in addition to a trend toward resolution of absence seizures (P =
      .08). Single-stage upfront complete callosotomy resulted in resolution of absence
      (P = .002), astatic (P < .0001), myoclonic (P = .007), and complex partial (P =
      .008) seizures in addition to a trend toward resolution of GTC (P = .06). In
      comparing a composite of subjects who underwent anterior two thirds callosotomy
      alone or 2-stage complete callosotomy before the second stage to complete the
      callosotomy with subjects who underwent upfront complete CC, a more favorable
      outcome was found in those with the upfront complete CC (P = .02). CONCLUSION:
      Single-stage upfront complete callosotomy is effective in relieving a broader
      spectrum of seizure types than anterior two thirds callosotomy or 2-stage
      complete callosotomy in children. The advantages of single-stage complete
      callosotomy must be weighed against the potentially higher risk of neurological
      and operative complications.

PMID- 24089048
TI  - Multimodality treatment of complex unruptured cavernous and paraclinoid
      aneurysms.
AB  - BACKGROUND: Unruptured aneurysms of the cavernous and paraclinoid internal
      carotid artery can be approached via microsurgical and endovascular approaches.
      Trends in treatment reflect a steady shift toward endovascular techniques.
      OBJECTIVE: To analyze our results with multimodal treatment. METHODS: We reviewed
      patients with unruptured cavernous and paraclinoid internal carotid artery
      aneurysms proximal to the posterior communicating artery treated at a single
      center from 2007 to 2012. Treatment included 4 groups: (1) stent-assisted
      coiling, (2) pipeline endovascular device (PED) flow diverter, (3) clipping, and
      (4) trapping/bypass. Follow-up was 2 to 60 months. RESULTS: The 109 aneurysms in
      102 patients were studied with the following treatment groupings: 41 were done
      with stent-assisted coiling, 24 with Pipeline endovascular device, 24 by
      microsurgical clipping, and 20 by trap/bypass. Group: (1) two percent had delayed
      significant intraparenchymal hemorrhage; (2) thirteen percent had central nerve
      palsies, 8% had small asymptomatic infarcts, and 4% had small, asymptomatic
      remote-site hemorrhages; (3) twenty-nine percent of patients suffered from
      transient central nerve palsies, 4% experienced major stroke, and 8% had small
      intracerebral hemorrhages; (4) thirty-five percent had transient central nerve
      palsies, 10% had strokes, and 10% had intracerebral hemorrhages. In terms of
      follow-up obliteration, 83% had complete/nearly complete obliteration at last
      follow-up, 17% had residual aneurysms, and 10% required retreatment. Ninety-six
      percent of group 1 (35/38), 100% of group 2 (23/23), 100% of group 3 (21/21), and
      95% of group 4 had modified Rankin Scale scores of 0 to 1. CONCLUSION: Treatment
      of these aneurysms can be carried out with acceptable rates of morbidity. Careful
      patient selection is crucial for optimal outcome. Endovascular treatment volumes
      likely will continue to predominate over microsurgical techniques as changing
      skill sets evolve in neurosurgery, but individualized application of all
      available treatment options will continue.

PMID- 24089049
TI  - Monitoring flow in extracranial-intracranial bypass grafts using duplex
      ultrasonography: a single-center experience in 80 grafts over 8 years.
AB  - BACKGROUND: High-flow extracranial-intracranial (EC-IC) bypass is performed by
      using radial artery graphs (RAGs) or saphenous vein grafts (SVGs) for various
      pathologies such as aneurysms, ischemia, and skull-base tumors. Quantifying the
      acceptable amount of blood flow to maintain proper cerebral perfusion has not
      been well established, nor have the variables that influence flow been
      determined. OBJECTIVE: To identify the normative range of blood flow through
      extracranial-intracranial RAGs and SVGs as measured by duplex ultrasonography.
      Multiple variables were evaluated to better understand their influence of graft
      flow. METHODS: All EC-IC grafts performed at Harborview Medical Center from 2005
      to 2012 were retrospectively reviewed for this cohort study. Daily extracranial
      graft duplex ultrasonography with flow volumes and transcranial graft Doppler
      were examined, as were short- and long-term outcomes. Both ischemic and hyperemic
      events were evaluated in further detail. RESULTS: Eighty monitorable high-flow EC
      IC bypasses were performed over the 8-year period. Sixty-five bypasses were
      performed by using RAGs and 15 were performed with SVGs. The average flow was 133
      mL/min for RAGs and 160 mL/min for SVGs (P = .25). For both RAG and SVG groups,
      the donor and recipient vessel selected significantly impacted flow. For the RAG
      group only, preoperative graft diameter, postoperative hematocrit, and
      postoperative date significantly influenced flow. A 1-week average of >200 mL/min
      was 100% sensitive to cerebral hyperemia syndrome. CONCLUSION: This study
      establishes the normative range of duplex ultrasonographic flow after high-flow
      EC-IC bypass, as well the usefulness and practicality of such monitoring as a
      surrogate to flow in the postoperative period.

PMID- 24089050
TI  - Real-time atlas-based stereotactic neuronavigation.
AB  - BACKGROUND: Surgery for tumors in eloquent brain faces immense challenges when
      attempting to maximize resection and avoid neurological deficits. OBJECTIVE: In
      order to give the surgeon real-time atlas-based anatomic information linked to
      the patient's anatomy, we developed a software-based interface between deformable
      anatomic templates (DATs) and an intraoperative navigation system. METHODS:
      Magnetic resonance imaging (MRI), diffusion tensor imaging, and/or functional MRI
      were performed on 3 patients preoperatively for the purposes of tumor resection
      by the use of neuronavigation. The DAT was registered to the patients' navigation
      coordinate system and utilized coordinates from the navigation system during
      surgery. This provided the surgeon with a list of proximal anatomic and
      functional structures and a real-time image of the atlas at that location fused
      to the patient's MRI. The clinical feasibility of this approach was evaluated
      during the resection of 3 eloquent tumors (right postcentral gyrus, left inferior
      frontal gyrus, and left occipital cuneus gyrus). RESULTS: Tumor resection was
      performed successfully in all 3 patients. With the use of the coordinates from
      the navigation system, anatomic and functional structures and their distances
      were visualized interactively during tumor resection by using the DAT.
      CONCLUSION: This is a proof of concept that an interactive atlas-based navigation
      can provide detailed anatomic and functional information that supplements MRI,
      diffusion tensor imaging, and functional MRI. The atlas-based navigation
      generated distances to important anatomic structures from the navigation probe
      tip. It can be used to guide direct electrical stimulation and highlight areas to
      avoid during tumor resection. ABBREVIATIONS: DAT, deformable anatomic
      templateDES, direct electrical stimulationDTI, diffusion tensor imagingfMRI,
      functional magnetic resonance imaging.

PMID- 24089051
TI  - Cystic glioblastoma: an evaluation of IDH1 status and prognosis.
AB  - BACKGROUND: Controversy exists regarding the prognostic significance of cystic
      features in newly diagnosed glioblastoma multiforme (GBM) and the pathological
      origin of cystic GBMs. OBJECTIVE: To determine whether cystic GBMs develop from
      low-grade gliomas by evaluating IDH1 status and to evaluate the differences in
      overall survival between patients with cystic and noncystic tumors. METHODS: We
      retrospectively reviewed the records of 351 consecutive newly diagnosed adult GBM
      patients treated at our institution from October 1997 to November 2011; patients
      with >50% cystic tumor composition were further identified. IDH1 mutation was
      determined by immunohistochemical staining. Patient characteristics and treatment
      were reported for cystic and noncystic tumors separately. Overall survival was
      reported for cystic and noncystic cohorts by using the Kaplan-Meier estimates.
      RESULTS: Of 351 patients, 27 (7.7%) had cystic tumors and 324 (92.3%) had
      noncystic tumors. Tumor samples for patients with cystic GBMs were
      immunohistochemically analyzed for IDH1 mutations. Two (7.4%) of the 27 tumor
      samples were documented as having IDH1 mutations. Characteristics such as age,
      sex, perioperative Karnofsky Performance Status, tumor size, extent of resection,
      postsurgery radiation, and temozolomide therapy were comparable in the and
      noncystic cohorts. Patients in the cystic cohort had a median overall survival of
      15.0 months compared with 18.2 months for the noncystic cohort (log-rank P =
      .77). CONCLUSION: The low frequency of IDH1 mutation status in our cystic cohort
      strongly suggests that most newly diagnosed cystic GBMs do not arise from
      malignant transformation of previously undiagnosed low-grade gliomas.
      Furthermore, there is no difference in overall survival between patients newly
      diagnosed with cystic and noncystic GBMs.

PMID- 24089052
TI  - The comprehensive neuro-oncology data repository (CONDR): a research
      infrastructure to develop and validate imaging biomarkers.
AB  - BACKGROUND: Advanced imaging methods have the potential to serve as quantitative
      biomarkers in neuro-oncology research. However, a lack of standardization of
      image acquisition, processing, and analysis limits their application in clinical
      research. Standardization of these methods and an organized archival platform are
      required to better validate and apply these markers in research settings and,
      ultimately, in clinical practice. OBJECTIVE: The primary objective of the
      Comprehensive Neuro-oncology Data Repository (CONDR) is to develop a data set for
      assessing and validating advanced imaging methods in patients diagnosed with
      brain tumors. As a secondary objective, informatics resources will be developed
      to facilitate the integrated collection, processing, and analysis of imaging,
      tissue, and clinical data in multicenter clinical trials. Finally, CONDR data and
      informatics resources will be shared with the research community for further
      analysis. METHODS: CONDR will enroll 200 patients diagnosed with primary brain
      tumors. Clinical, imaging, and tissue-based data are obtained from patients
      serially, beginning with diagnosis and continuing over the course of their
      treatment. The CONDR imaging protocol includes structural and functional
      sequences, including diffusion- and perfusion-weighted imaging. All data are
      managed within an XNAT-based informatics platform. Imaging markers are assessed
      by correlating image and spatially aligned pathological markers and a variety of
      clinical markers. EXPECTED OUTCOMES: CONDR will generate data for developing and
      validating imaging markers of primary brain tumors, including multispectral and
      probabilistic maps. DISCUSSION: CONDR implements a novel, open-research model
      that will provide the research community with both open-access data and open
      source informatics resources.

PMID- 24089053
TI  - Transcriptional repressor HipB regulates the multiple promoters in Escherichia
      coli.
AB  - HipB is a DNA-binding protein in Escherichia coli and negatively regulates its
      own promoter by binding to the palindromic sequences [TATCCN8GGATA (N represents
      any nucleotides)] on the hipBA promoter. For such sequences, bioinformatic
      analysis revealed that there are a total of 39 palindromic sequences
      (TATCCN(x)GGATA: N is any nucleotides and x is the number of nucleotides from 1
      to 30) in the promoter regions of 33 genes on the E. coli genome. Notably, eutH
      and fadH have two and three TATCCN(x)GGATA palindromic sequences located in their
      promoters, respectively. Another significant finding was that a palindromic
      sequence was also identified in the promoter region of hipAB locus, known to be
      involved in the RelA-dependent persister cell formation in bacteria. Here, we
      demonstrated that HipB binds to the palindromic structures in the eutH, fadH, as
      well as the relA promoter regions and represses their expressions. We further
      demonstrated that HipA enhances the repression of the relA promoter activity by
      HipB. This effect was not observed with D291A HipA mutant which was previously
      shown to lack an ability to interact with HipB, indicating that HipA enhances the
      HipB's repressor activity through direct interaction with HipB.

PMID- 24089054
TI  - Add-on treatment of benzoate for schizophrenia: a randomized, double-blind,
      placebo-controlled trial of D-amino acid oxidase inhibitor.
AB  - IMPORTANCE: In addition to dopaminergic hyperactivity, hypofunction of the N
      methyl-d-aspartate receptor (NMDAR) has an important role in the pathophysiology
      of schizophrenia. Enhancing NMDAR-mediated neurotransmission is considered a
      novel treatment approach. To date, several trials on adjuvant NMDA-enhancing
      agents have revealed beneficial, but limited, efficacy for positive and negative
      symptoms and cognition. Another method to enhance NMDA function is to raise the
      levels of d-amino acids by blocking their metabolism. Sodium benzoate is a d
      amino acid oxidase inhibitor. OBJECTIVE: To examine the clinical and cognitive
      efficacy and safety of add-on treatment of sodium benzoate for schizophrenia.
      DESIGN, SETTING, AND PARTICIPANTS: A randomized, double-blind, placebo-controlled
      trial in 2 major medical centers in Taiwan composed of 52 patients with chronic
      schizophrenia who had been stabilized with antipsychotic medications for 3 months
      or longer. INTERVENTIONS: Six weeks of add-on treatment of 1 g/d of sodium
      benzoate or placebo. MAIN OUTCOMES AND MEASURES: The primary outcome measure was
      the Positive and Negative Syndrome Scale (PANSS) total score. Clinical efficacy
      and adverse effects were assessed biweekly. Cognitive functions were measured
      before and after the add-on treatment. RESULTS: Benzoate produced a 21%
      improvement in PANSS total score and large effect sizes (range, 1.16-1.69) in the
      PANSS total and subscales, Scales for the Assessment of Negative Symptoms-20
      items, Global Assessment of Function, Quality of Life Scale and Clinical Global
      Impression and improvement in the neurocognition subtests as recommended by the
      National Institute of Mental Health's Measurement and Treatment Research to
      Improve Cognition in Schizophrenia initiative, including the domains of
      processing speed and visual learning. Benzoate was well tolerated without
      significant adverse effects. CONCLUSIONS AND RELEVANCE: Benzoate adjunctive
      therapy significantly improved a variety of symptom domains and neurocognition in
      patients with chronic schizophrenia. The preliminary results show promise for d
      amino acid oxidase inhibition as a novel approach for new drug development for
      schizophrenia.

PMID- 24089055
TI  - Metastasis-associated protein 1 is an integral component of the circadian
      molecular machinery.
AB  - The mammalian circadian clock regulates the daily cycles of many important
      physiological processes, but its mechanism is not well understood. Here we
      provide genetic and biochemical evidence that metastasis-associated protein 1
      (MTA1), a widely upregulated gene product in human cancers, is an integral
      component of the circadian molecular machinery. Knockout of MTA1 in mice disrupts
      the free-running period of circadian rhythms under constant light and normal
      entrainment of behaviour to 12-h-light/12-h-dark cycles. The CLOCK-BMAL1
      heterodimer activates MTA1 transcription through a conserved E-box element at its
      promoter. MTA1, in turn, interacts with and recruits CLOCK-BMAL1 at its own and
      CRY1 promoters and promotes their transcription. Moreover, MTA1 deacetylates
      BMAL1 at lysine 538 through regulating deacetylase SIRT1 expression, thus
      disturbing the CRY1-mediated negative feedback loop. These findings uncover a
      previously unappreciated role for MTA1 in maintenance of circadian rhythmicity
      through acting on the positive limb of the clock machinery. 

PMID- 24089056
TI  - The paradox of enrichment in phytoplankton by induced competitive interactions.
AB  - The biodiversity loss of phytoplankton with eutrophication has been reported in
      many aquatic ecosystems, e.g., water pollution and red tides. This phenomenon
      seems similar, but different from the paradox of enrichment via trophic
      interactions, e.g., predator-prey systems. We here propose the paradox of
      enrichment by induced competitive interactions using multiple contact process (a
      lattice Lotka-Volterra competition model). Simulation results demonstrate how
      eutrophication invokes more competitions in a competitive ecosystem resulting in
      the loss of phytoplankton diversity in ecological time. The paradox is enhanced
      under local interactions, indicating that the limited dispersal of phytoplankton
      reduces interspecific competition greatly. Thus, the paradox of enrichment
      appears when eutrophication destroys an ecosystem either by elevated
      interspecific competition within a trophic level and/or destabilization by
      trophic interactions. Unless eutrophication due to human activities is ceased,
      the world's aquatic ecosystems will be at risk. 

PMID- 24089057
TI  - Improvement of hepatic lesion characterization by 18F-FDG PET/CT with the use of
      the lesion to background liver activity ratio.
AB  - OBJECTIVE: This study aimed to develop a reproducible method to improve (18)F-FDG
      PET/CT's diagnostic accuracy when characterizing hepatic lesions. METHODS: This
      was a retrospective study of 76 patients with various types of cancer who had 134
      liver lesions described on diagnostic CT, MRI, or (18)F-FDG PET/CT. All 134
      lesions were imaged by PET/CT. For comparison, all 134 lesions were also imaged
      either by MRI (58 lesions) or by diagnostic CT (107), with some imaged by both.
      The original reader's interpretation was used to determine the diagnostic
      validity of each modality. The (18)F-FDG PET/CT findings were then re-stratified
      using the ratio of the SUV(max) of the liver lesion to the SUV(avg) of liver
      background (SUV(TLR)). The standard of reference was histopathology and/or
      imaging follow-up. Eighty-nine out of the 134 lesions were positive for
      metastases. Two-tailed P values were calculated using a chi-square test. RESULTS:
      A SUV(TLR) greater than 2.0 strongly correlated with metastasis, while less than
      2.0 strongly correlated with benign activity. Based on the original interpreter's
      visual analysis (PET(VA)), (18)F-FDG PET/CT had an accuracy of 74.6% with a high
      sensitivity (95.5%), but limited specificity (33.3%). Using the SUV(TLR) cutoff
      value of 2.0 to objectively re-stratify these cases, there was improvement in
      accuracy to 97.8%, sensitivity to 100%, and specificity to 93.3%. These values
      were statistically significant by chi-square analysis, with P = 0.0001 for both
      PET(VA) and SUV(TLR). The 58 MRI lesions and 107 diagnostic CT lesions that were
      reviewed had accuracies of 70.7% (P = 0.008) and 73.8% (P = 0.0001),
      respectively. CONCLUSION: Using a cutoff value of 2.0 for SUV(TLR) to objectively
      evaluate for potential hepatic metastases on (18)F-FDG PET results in a
      significant improvement in diagnostic accuracy over subjective visual analysis
      alone. In this limited study, use of SUV(TLR) more accurately characterized
      hepatic lesions than the original CT or MRI interpretations.

PMID- 24089058
TI  - Effect of intragastric balloon on gastric emptying time in humans for weight
      control.
AB  - PURPOSE: This study evaluated the effect of fluid-filled intragastric balloon
      treatment on the scintigraphic gastric emptying times in humans for weight
      control. PATIENTS AND METHODS: Ten obese patients were prospectively recruited in
      our study. Three participants followed a solid food diet, and 7 participants
      followed a liquid meal diet to evaluate their scintigraphic gastric emptying
      times before and 3 months after fluid-filled intragastric balloon treatment.
      RESULTS: The participants included 3 males and 7 females. The mean age, body mass
      index, and body weight before intragastric balloon treatment were 36.8 +/- 9.16
      years, 35.91 +/- 8.86 kg/m(2), and 93.9 +/- 24.09 kg, respectively. The mean body
      weight, body mass index, and body weight loss 3 months after the treatment were
      80.2 +/- 21.32 kg, 31.50 +/- 8.90 kg/m(2), and 13.7 +/- 6.60 kg, respectively.
      The solid gastric emptying times before and 3 months after intragastric balloon
      treatment were 114 +/- 18.52 minutes and 375.33 +/- 207.04 minutes, respectively.
      The liquid gastric emptying times before and after intragastric balloon treatment
      were 38.71 +/- 15.91 minutes and 318.71 +/- 168.07 minutes, respectively.
      Statistically significant differences were observed in the solid and liquid
      gastric emptying times before and 3 months after intragastric balloon treatment
      using the Wilcoxon t test (P = 0.027, P = 0.001). Significantly positive
      correlations were observed between body weight loss and solid and liquid gastric
      emptying times after intragastric balloon placement using the Spearman
      correlation (beta = 1.0, P < 0.001; beta = 0.95, P = 0.001). CONCLUSIONS: The
      solid and liquid scintigraphic gastric emptying half time is significantly longer
      after intragastric balloon treatment in humans. A significantly positive
      correlation between body weight loss and scintigraphic gastric emptying time was
      observed after intragastric balloon treatment. We can predict the effect of
      intragastric balloons on weight control through scintigraphic gastric emptying
      times after the treatment. The effect of intragastric balloons on weight loss may
      be reinforced by combining intragastric balloon treatment with medication that
      can reduce gastric motility.

PMID- 24089059
TI  - Osteomalacia-inducing renal clear cell carcinoma uncovered by 99mTc
      Hydrazinonicotinyl-Tyr3-octreotide (99mTc-HYNIC-TOC) scintigraphy.
AB  - Most osteomalacia-causing tumors are small, benign mesenchymal neoplasms, which
      are commonly located in the extremities or craniofacial regions. An 18-year-old
      male patient with suspicion of tumor-induced osteomalacia underwent (99m)Tc-HYNIC
      TOC scintigraphy to search potential culprit tumor. The images showed a large
      activity in the region of the left kidney. The lesion was resected and a clear
      cell renal cell carcinoma was found. One year after the left nephrectomy, the
      patient was tumor-free without symptoms of osteomalacia.

PMID- 24089061
TI  - Benign adrenal hemangiomas may mimic metastases on PET.
AB  - CT or MRI are utilized in the initial evaluation of adrenal incidentalomas;
      however, overlap exists between benign and malignant lesions on these
      examinations. The American College of Radiology recommends PET scans to
      complement CT and MRI for patients with adrenal masses and a moderate-to-high
      likelihood of neoplastic disease. We present images of a PET-avid adrenal lesion
      in a patient with pulmonary and pancreatic neoplasms that mimicked metastasis,
      but was found to be a benign adrenal hemangioma on surgical resection. The use of
      PET for adrenal tumors, specifically adrenal hemangiomas, will be reviewed. 

PMID- 24089060
TI  - (99m)Tc sestamibi as a prognostic factor of response to first-line therapy and
      outcome in patients with malignant lymphoma.
AB  - INTRODUCTION: Resistance to chemotherapy poses a major problem in cancer
      patients. Although of multifactorial origin, some of the implicated mechanisms
      also interfere with (99m)Tc-MIBI uptake and retention in cancer cells. The aim of
      the current study was to investigate the prognostic value of baseline (99m)Tc
      MIBI imaging in lymphoma. METHODS: (99m)Tc-MIBI SPECT was performed in 16
      patients with Hodgkin lymphoma and 31 with non-Hodgkin lymphoma (NHL) before
      chemotherapy initiation. Early (20 minutes), late (120 minutes) tumor-to
      background (T/B) ratios, and 2-hour (99m)Tc-MIBI washout were calculated. Follow
      up data were obtained for a period of 45.5 +/- 23.5 months. Study end points were
      response to first-line chemotherapy, lymphoma-related death (LRD), and time to
      disease progression. RESULTS: Of the scintigraphic indices examined, the late T/B
      ratio correlated best with study end points. A cutoff value of 1.8 determined by
      receiver operating characteristic analysis discriminated poor from good response
      and LRD from survival with an accuracy of 87% and 81%, respectively. Kaplan-Meier
      survivor functions separated by this cutoff differed significantly for both time
      to disease progression and LRD (P = 0.0001 and P = 0.0015). In the Cox
      proportional hazards model, the late T/B ratio proved to have an independent and
      incremental value over clinical prognostic factors (age, lymphoma type, Ann Arbor
      stage, lactate dehydrogenase levels) and, in NHL patients, over the international
      prognostic index. Patients with high international prognostic index score could
      be further stratified into different prognostic categories. CONCLUSION: The
      current study indicates that baseline (99m)Tc-MIBI SPECT can provide useful
      prognostic information in patients with lymphoma, particularly NHL, regarding
      therapy response and final outcome.

PMID- 24089062
TI  - FDG-anorectic parathyroid carcinoma with FDG-avid bone metastasis on PET/CT
      images.
AB  - A 53-year-old man complained of aggravated left hip pain of more than 2 months.
      Whole-body (18)F-FDG PET/CT revealed only 1 hypermetabolic lesion in the left
      ilium. Histopathologic examination of the lesion suggested metastatic disease.
      Blood tests documented mildly elevated blood calcium and parathyroid hormone.
      Subsequent neck ultrasonography, contrast-enhanced CT, and dual-phase
      scintigraphy with (99m)Tc-MIBI showed a right parathyroid tumor, which was
      confirmed to be a parathyroid carcinoma postoperatively. We report a case of
      parathyroid carcinoma rarely encountered with a FDG-negative primary but a FDG
      positive metastasis on PET/CT images.

PMID- 24089064
TI  - Atypical bilateral stress fractures of the femoral shaft diagnosed by bone
      scintigraphy in a woman with osteoporosis.
AB  - Recent case series have identified the presence of atypical insufficiency
      fractures at the diaphyseal femur of osteoporotic patients, which are possibly
      related to the long-term use of biphosphonates. We present images of a 72-year
      old woman with a history of colon cancer and osteoporosis referred for bone
      scintigraphy because of bilateral thigh pain. No trauma or intense exercise was
      reported. Bone scan revealed bilateral femoral shaft stress fractures, which were
      confirmed by plain radiographs. In oncologic patients with osteoporosis referred
      for bone scintigraphy, atypical stress fractures should be included in the
      differential diagnosis of focal findings in the diaphyseal femur. 

PMID- 24089063
TI  - Evaluation of headache and regional cerebral flood flow in patients with
      migraine.
AB  - PURPOSE OF THE REPORT: The aim of this study is to observe the abnormalities of
      regional cerebral blood flow (rCBF) in migraine patients and to evaluate its
      relation to the severity of the headache in patients with migraine. PATIENTS AND
      METHODS: The rCBF imaging was done on 19 patients with migraine and 15 normal
      controls using single-photon emission computed tomography (SPECT). The abnormal
      character of cerebral perfusion function was analyzed with Statistical Parametric
      Mapping (SPM) software, and the headache grade of patients was evaluated with the
      headache severity measuring scale. RESULTS: The results of SPM analysis
      demonstrated a decreased rCBF on both sides of the frontal and temporal lobes,
      left parietal lobe, and right occipital lobe (P < 0.001), and increased rCBF
      focus on the left prefrontal lobe and right temporal lobe (P < 0.001). The
      headache scores in migraineurs were correlated to the rCBF on the bilateral
      temporal lobes and right frontal lobe (P < 0.001). CONCLUSIONS: The migraineurs
      had lower rCBF at the frontal and temporal lobes, and the lower rCBF was
      correlated to the degree of headache.

PMID- 24089065
TI  - An unusual urine leak with urolithiasis.
AB  - Urine leaks usually result from blunt or penetrating trauma to the kidneys.
      Occasionally, urine leaks can be caused by back pressure from urinary obstruction
      caused by large urinary stones or a pelvic mass. We present the case of a 56-year
      old man with an unusual urine leak caused by a small 2-mm renal stone. 

PMID- 24089066
TI  - Cerebral infarction on 99mTc-MDP SPECT/CT imaging.
AB  - A 70-year-old man with lung cancer underwent whole-body MDP bone scintigraphy to
      evaluate bone metastases that showed marked tracer uptake in the right side of
      the head, suggestive of skull metastasis. SPECT/CT imaging was performed for
      further evaluation. The SPECT images demonstrated increased MDP activity in the
      region of the brain perfused by the right middle cerebral artery. On CT images,
      there was a large hypoattenuation area corresponding to elevated MDP
      accumulation. At the same day, magnetic resonance angiography of the brain
      revealed occlusion of the right middle cerebral artery. 

PMID- 24089067
TI  - Pulmonary embolism caused by right atrial myxoma on FDG PET/CT.
AB  - Pulmonary embolism derived from the right atrial myxoma is a rare event and can
      be difficult to recognize. A chest x-ray image from a 48-year-old woman with
      shortness of breath revealed multiple pulmonary nodules, which suggested lung
      metastases. An FDG PET/CT was performed for further evaluation. The images showed
      that the lung nodules had variable but mild FDG activity in general. There was 1
      additional large FDG activity in the right atrium. The subsequent studies
      demonstrated that the patient experienced pulmonary embolism derived from the
      right atrial myxoma. 

PMID- 24089068
TI  - Diagnosis and follow-up of chronic bacterial prostatitis with recurrent urinary
      tract infection detected by 67Ga scintigraphy and SPECT/CT.
AB  - Half of male populations will have symptoms and signs of prostatitis in their
      lifetime. There is controversy concerning diagnosis of prostatitis with (67)Ga
      scintigraphy because the focal midline pelvic uptake is usually considered to be
      physiologic uptake in colon. The authors describe (67)Ga scintigraphy and
      SPECT/CT findings of a 58-year-old man with right flank pain and fever. The
      examination demonstrated abnormal uptake of Ga within the prostate and right
      kidney upper pole, suggesting prostatitis and acute pyelonephritis (APN)
      contemporary. After completion of antibiotic treatment, follow-up scintigraphy
      and SPECT/CT showed complete resolution of APN, but uptake remained within the
      prostate.

PMID- 24089069
TI  - Lymphoscintigraphy in the evaluation of limb edema.
AB  - Lymphedema is a chronic condition caused by ineffective lymphatic transport that
      results in edema and skin damage. Distinguishing lymphedema from other causes can
      be difficult. Lymphoscintigraphy is a simple and noninvasive functional test for
      the evaluation of the lymphatic system. (99m)Technetium-labeled sulfur colloid is
      injected intradermally at the interdigital web spaces of the upper/lower limbs.
      Once injected, the radiolabeled colloid particles travel through the superficial
      lymphatic channels. Thus, their lymphatic transport is monitored with dual-head
      gamma camera. The typical patterns of upper and lower limb lymphedema on
      lymphoscintigraphy are summarized in this section.

PMID- 24089070
TI  - Tips for a physician in getting the right job, part IV: types of interviews for a
      clinical position.
AB  - Most physicians interviewing for a job are seeking a clinical position. There are
      many different types of interviews for such employment, and this article
      enumerates the types of interviews and some characteristics of each. 

PMID- 24089071
TI  - Advantages of pinhole collimator double-phase scintigraphy with 99mTc-MIBI in
      secondary hyperparathyroidism.
AB  - PURPOSE: The aim of the study was to determine if pinhole collimator-acquired
      images can improve the detection of hyperfunctioning parathyroid glands in
      patients with secondary hyperparathyroidism. METHODS: Forty-two patients being
      treated with cinacalcet for secondary hyperparathyroidism were studied
      prospectively. Patients were divided into 2 groups according to their levels of
      parathyroid hormone (PTH), the hormone that defines response to treatment:
      "responders" (PTH <300 pg/mL) and "nonresponders" (PTH >= 300 pg/mL). Double
      phase scintigraphy using 888 MBq of (99m)Tc-MIBI was used to acquire early and
      late parallel-hole and pinhole collimator images. Neck ultrasonography was
      performed on all patients to identify intrathyroid nodules. All focal uptake in
      any of the acquired scintigraphic images was considered positive. RESULTS: The
      responder group included 24 patients, whereas 18 patients were considered as
      nonresponders. At least 1 parathyroid gland with (99m)Tc-MIBI uptake was detected
      in 33 of 42 patients, with a total of 50 parathyroid glands located. We found
      significant differences between the detection rates of late pinhole collimator
      and the late parallel-hole images (74% vs 48%, P = 0.0036). This detection rate
      was highest with late parallel-hole images in the nonresponder group (89%).
      CONCLUSIONS: The late pinhole collimator acquisition showed the highest detection
      rate of hyperfunctioning parathyroid glands using (99m)Tc-MIBI scintigraphy in
      secondary hyperparathyroidism patients treated with cinacalcet.

PMID- 24089072
TI  - Routine micromethod for the determination of vitamin K1 in human plasma.
AB  - BACKGROUND: A selective and sensitive high-performance liquid chromatographic
      method with fluorescence detection after postcolumn reduction is described for
      the routine measurement of vitamin K1 in plasma samples of 100 uL of volume.
      METHODS: Liquid-liquid extraction was used for the sample preparation with
      vitamin K2 as an internal standard. For the chromatographic separation, a
      standard C18 column was applied. The calibration range used was from 2 to 500
      ng/mL. RESULTS: At the low level (5 ng/mL), a coefficient of variation of 14.9%
      was observed interday in the quality control samples, whereas at the intermediate
      (50 ng/mL) and high (200 ng/mL) levels such of 6.8% and 8.7% were found.
      CONCLUSIONS: The method has proven robust and convenient for the analysis of
      samples from clinical pharmacological studies.

PMID- 24089073
TI  - Association between inherited CYP2D6/2C19 phenotypes and anticholinergic measures
      in elderly patients using anticholinergic drugs.
AB  - BACKGROUND: To compare measures of anticholinergic activity between metabolic
      phenotypes of the polymorphic enzymes cytochrome P450 2D6 (CYP2D6) and CYP2C19 in
      the elderly patients exposed to anticholinergic agents. METHODS: Long-term
      nursing home patients (n = 80) with an anticholinergic drug scale (ADS) score >=3
      were recruited from 22 nursing homes in Norway. Based on pharmacogenetic analyses
      of mutations encoding absent CYP2D6 or CYP2C19 metabolism, patients were divided
      into subgroups of poor metabolizers (PMs) (n = 8) and extensive metabolizers (n =
      72). Serum anticholinergic activity (SAA) was determined by a validated, 96-well
      format radio receptor assay and adjusted for ADS score. Unadjusted and adjusted
      SAAs, mouth dryness, and cognitive function (Mini-Mental State Examination and
      verbal recall tests from Consortium to Establish a Registry for Alzheimer
      Disease) were compared between the subgroups with Mann-Whitney tests. RESULTS:
      The study population was represented by 78% women, 68% had mild to moderate
      dementia, and mean age was 86 years. More than 80% used more than 1
      anticholinergic agent, and their median ADS score was 4. The subpopulation of PMs
      had significantly higher median SAA than the extensive metabolizers (10.3 versus
      4.2 pmol atropine equivalents per milliliter, P = 0.012). This difference
      remained significant after adjusting for ADS score (P = 0.013). No significant
      differences in mouth dryness and cognitive function were observed between the
      subgroups (P > 0.3). CONCLUSIONS: These preliminary findings suggest that elderly
      CYP2D6/CYP2C19 PMs with a high anticholinergic drug burden are at increased risk
      of elevated SAA. Whether PMs are also more prone to experience anticholinergic
      side effects needs to be further studied in larger patient populations.

PMID- 24089074
TI  - Population pharmacokinetics of tacrolimus in adult kidney transplant patients:
      impact of CYP3A5 genotype on starting dose.
AB  - OBJECTIVES: The aims of this study were to develop a population pharmacokinetic
      model of tacrolimus in adult kidney transplant recipients, to use this model to
      compare cytochrome P450 3A5 (CYP3A5) genotype-based initial dosing of tacrolimus
      with standard per-kilogram-based dosing, and to predict the best starting dose of
      tacrolimus based on patient genotype to achieve a trough concentration between 6
      and 10 ug/L by day 5 posttransplantation. METHODS: Population analysis was
      performed using the software program NONMEM. Tacrolimus dosing regimens were
      compared by predicting tacrolimus trough concentrations in a simulated data set
      by running NONMEM with population parameters fixed at the final model estimates.
      Data from 173 patients with 1554 tacrolimus concentration-time measurements were
      modeled. RESULTS: Tacrolimus disposition was well described by a 2-compartment
      model with first-order elimination and first-order absorption after a lag time.
      Patient CYP3A5 genotype (rs776746), weight, hematocrit, and postoperative day
      were identified as significant covariates effecting tacrolimus apparent oral
      clearance (CL/F), with higher CL/F in CYP3A5*1 allele carriers, heavier patients,
      patients with low hematocrit, and in the immediate posttransplantation period.
      Typical population estimates for tacrolimus CL/F in CYP3A5*1 allele carriers and
      noncarriers were 40.8 and 25.5 L/h, respectively. CONCLUSIONS: In patients
      carrying the CYP3A5*1 allele, a per-kilogram dose of 0.075 mg/kg twice daily
      seemed too much low with approximately 65% of simulated subjects predicted to
      achieve a trough below 6 ug/L at day 5 posttransplantation. To reduce the risk of
      under immunosuppression in the immediate posttransplantation period, carriers of
      a CYP3A5*1 allele are likely to benefit from a tacrolimus starting dose of either
      10 mg or 0.115 mg/kg twice daily.

PMID- 24089076
TI  - P450 oxidoreductase *28 (POR*28) and tacrolimus disposition in pediatric kidney
      transplant recipients--a pilot study.
AB  - BACKGROUND: Both age and CYP3A5 genotype are important determinants of tacrolimus
      disposition in pediatric kidney transplant recipients. In a recent study in
      adults, POR*28 was associated with increased dosing requirements early after
      transplant of CYP3A5-expressing kidney transplant recipients. The authors aimed
      to evaluate the additional contribution of POR*28 to early tacrolimus disposition
      in pediatric kidney transplant recipients. METHODS: Retrospective data of 43
      pediatric kidney transplant recipients up to 14 days posttransplant were
      evaluated on tacrolimus dose and tacrolimus predose blood concentrations.
      Recipient POR*28 and CYP3A5 genotype were determined. RESULTS: CYP3A5 expressers
      carrying at least 1 POR*28 allele had on average 18.3% lower tacrolimus predose
      concentrations and 20.2% lower concentration/dose ratios compared with CYP3A5
      expressers with POR*1/*1 genotype (P = 0.002 and P = 0.001, respectively). In
      CYP3A5 nonexpressers, tacrolimus disposition did not significantly differ between
      POR genotypes. CONCLUSIONS: In this small cohort of pediatric kidney transplant
      recipients, POR*28 genotype seems to explain part of the variability found in
      tacrolimus disposition, in addition to age and CYP3A5 genotype. This finding
      should be validated in a larger population, and it would be worthwhile to
      evaluate the clinical impact of this genotype.

PMID- 24089075
TI  - A randomized double-blind clinical trial of a continuous 96-hour levobupivacaine
      infiltration after open or laparoscopic colorectal surgery for postoperative pain
      management--including clinically important changes in protein binding.
AB  - BACKGROUND: Continuous local anesthetic infiltration has been used for pain
      management after open colorectal surgery. However, its application to patients
      undergoing laparoscopic colorectal surgery has not been examined. The aim of this
      prospective, randomized, double-blind, placebo-controlled clinical trial was to
      study the use of a commercial infiltration device in patients undergoing open or
      laparoscopic colorectal surgery, along with plasma concentrations of
      levobupivacaine, its acute-phase binding protein (alpha-1 acid glycoprotein,
      AAG), and the stress marker, cortisol. METHODS: Eligible patients were randomized
      (2:1) to receive a continuous infiltration of either levobupivacaine or placebo
      using a commercial device (ON-Q PainBuster) inserted in the preperitoneal layer
      at the end of surgery. Blood was sampled for determination of levobupivacaine and
      AAG and cortisol concentrations. Other outcomes measured were pain scores,
      morbidity and mortality, time to bowel movement, mobilization, and length of
      hospitalization. RESULTS: In patients having open surgery, the levobupivacaine
      treatment showed a trend toward reduced total opioid consumption. No patients
      reported adverse effects attributable to levobupivacaine, despite 11 patients
      having concentrations at some time(s) during the 96-hour infiltration of up to
      5.5 mg/L exceeding a putative toxicity threshold of 2.7 mg/L. AAG concentrations
      measured postsurgery increased by a mean of 55% (P < 0.001) at 48 hours. Cortisol
      concentrations also increased significantly by a mean of 191% at 1 hour.
      CONCLUSIONS: Continuous local anesthetic infiltration may be more beneficial in
      open surgery. The threshold for adverse effects from highly bound local
      anesthetic drugs established in healthy volunteers is of limited usefulness in
      clinical scenarios in which AAG concentration increases in response to surgical
      stress. Hence, there is scope to adopt higher doses to enhance therapeutic
      benefit.

PMID- 24089077
TI  - Wetland-based passive treatment systems for gold ore processing effluents
      containing residual cyanide, metals and nitrogen species.
AB  - Gold extraction operations generate a variety of wastes requiring responsible
      disposal in compliance with current environmental regulations. During recent
      decades, increased emphasis has been placed on effluent control and treatment, in
      order to avoid the threat to the environment posed by toxic constituents. In many
      modern gold mining and ore processing operations, cyanide species are of most
      immediate concern. Given that natural degradation processes are known to reduce
      the toxicity of cyanide over time, trials have been made at laboratory and field
      scales into the feasibility of using wetland-based passive systems as low-cost
      and environmentally friendly methods for long-term treatment of leachates from
      closed gold mine tailing disposal facilities. Laboratory experiments on discrete
      aerobic and anaerobic treatment units supported the development of design
      parameters for the construction of a field-scale passive system at a gold mine
      site in northern Spain. An in situ pilot-scale wetland treatment system was
      designed, constructed and monitored over a nine-month period. Overall, the
      results suggest that compost-based constructed wetlands are capable of
      detoxifying cyanidation effluents, removing about 21.6% of dissolved cyanide and
      98% of Cu, as well as nitrite and nitrate. Wetland-based passive systems can
      therefore be considered as a viable technology for removal of residual
      concentrations of cyanide from leachates emanating from closed gold mine tailing
      disposal facilities. 

PMID- 24089078
TI  - Near-infrared light-triggered irreversible aggregation of poly(oligo(ethylene
      glycol) methacrylate)-stabilised polypyrrole nanoparticles under biologically
      relevant conditions.
AB  - We report the use of near-infrared (NIR) radiation to trigger the irreversible
      flocculation of poly(oligo(ethylene glycol) methacrylate)-stabilised polypyrrole
      nanoparticles in physiological buffer. 

PMID- 24089080
TI  - Prevention of vitamin D deficiency during infancy is achieved by a combination of
      low-dose maternal and infant supplementation.

PMID- 24089081
TI  - A study of technetium-99m wastage in selected private sector nuclear medicine
      imaging departments.
AB  - BACKGROUND: South African nuclear medicine imaging departments have been
      fortunate in being able to receive an uninterrupted supply of molybdenum-99
      (99Mo)/technetium-99m (99mTc) generators. Nuclear medicine radiographers
      practising in private sector services in the northern Gauteng region indicated a
      possible problem with the quantities of wasted and unused 99mTc
      radiopharmaceuticals returned to the radiopharmaceutical supply laboratory. Daily
      radiopharmaceutical deliveries are a combination of ordered packages and standard
      packages. The purpose of the standard package is to accommodate emergency and
      after-hours nuclear medicine services. The purpose of the study was to
      interrogate the unconfirmed reports of 99mTc radiopharmaceutical wastage.
      METHODS: A descriptive quantitative research design was conducted in six private
      sector nuclear medicine imaging practices in the northern Gauteng region. Overt
      observations of the quantities of radiopharmaceutical supply, usage and wastage
      were conducted over 2 days in each of these practices. RESULTS: Ordered packages
      comprised 14% of the total 99mTc radiopharmaceutical deliveries to these six
      nuclear medicine imaging departments. It was identified that:(1) a total of 83.2%
      of ordered packages and 35.1% of standard packages of preprepared syringes were
      utilized;(2) a total of 36% of ordered packages and 22.6% of standard packages of
      bulk 99mTc were utilized; and (3) a total of 70.6% of the total quantity of
      radiopharmaceuticals was returned to the radiopharmaceutical laboratory. The
      total wastage represented 45.5% of the ordered packages and 75.8% of the standard
      packages. CONCLUSION: Wastage of 74 GBq of 99mTc from six sites over 12 days
      should raise concerns for the nuclear medicine industry. A review of the system
      framework that supports communication between the radiopharmaceutical supplier/s
      and the nuclear medicine imaging practices is recommended.

PMID- 24089082
TI  - Comparative serum proteomic analysis identified afamin as a downregulated protein
      in papillary thyroid carcinoma patients with non-131I-avid lung metastases.
AB  - BACKGROUND: The loss of 131I uptake ability in metastases from differentiated
      thyroid carcinoma (DTC) is becoming a major obstacle in radioiodine treatment.
      However, there is no effective way to screen for 131I uptake ability in
      metastases. The identification of differentially expressed proteins by serum
      proteomics may contribute to our understanding of the mechanisms underlying the
      dedifferentiation of DTC. MATERIALS AND METHODS: Serum samples were obtained from
      papillary thyroid carcinoma patients with non-131I-avid lung metastases and 131I
      avid lung metastases. Differential protein analysis was performed using two
      dimensional gel electrophoresis. Candidate protein spots showing differences in
      expression between the two groups were identified by means of matrix-assisted
      laser desorption/ionization time-of-flight mass spectrometry and were validated
      by western blotting. RESULTS: We found that afamin is downregulated in the serum
      of papillary thyroid carcinoma patients with non-131I-avid lung metastases.
      CONCLUSION: Afamin may be a potential serum biomarker for early screening of 131I
      uptake ability in DTC metastases and could therefore be of value in guiding
      radioiodine treatment decisions.

PMID- 24089084
TI  - Multi-analytical evaluation of serum levels of cytokines and adhesion molecules
      in patients treated for acute myeloid leukemia using biochip array technology.
AB  - AIMS: Evaluation of serum levels of 17 cytokines and 5 adhesion molecules in
      patients treated for acute myeloid leukemia (AML) using biochip array technology.
      This approach allows multi-analytical determination from a single sample.
      METHODS: A total of 15 AML patients were studied. Blood samples were taken at the
      diagnosis (active leukemia) and at circa 6 months after completion of last
      chemotherapy (durable complete remission in all patients). RESULTS: Comparing
      cytokine and adhesion molecule levels in active leukemia and in durable complete
      remission, we found significant increase (P<0.01) in serum interleukin-7 (IL-7),
      epidermal growth factor (EGF), vascular endothelial growth factor (VEGF), and
      significant decrease (P<0.01) in serum E-selectin. DISCUSSION: Our results
      indicate that serum levels of specific cytokines and adhesion molecules (IL-7,
      EGF, VEGF, E-selectin) are significantly altered in patients treated for AML,
      reflecting activity of the disease. Further investigation is needed to establish
      if the changes observed in the levels of these molecules could be used as a
      prognostic indicator of AML.

PMID- 24089083
TI  - H+-type and OH- -type biological protonic semiconductors and complementary
      devices.
AB  - Proton conduction is essential in biological systems. Oxidative phosphorylation
      in mitochondria, proton pumping in bacteriorhodopsin, and uncoupling membrane
      potentials by the antibiotic Gramicidin are examples. In these systems, H(+) hop
      along chains of hydrogen bonds between water molecules and hydrophilic residues -
      proton wires. These wires also support the transport of OH(-) as proton holes.
      Discriminating between H(+) and OH(-) transport has been elusive. Here, H(+) and
      OH(-) transport is achieved in polysaccharide- based proton wires and devices. A
      H(+)- OH(-) junction with rectifying behaviour and H(+)-type and OH(-)-type
      complementary field effect transistors are demonstrated. We describe these
      devices with a model that relates H(+) and OH(-) to electron and hole transport
      in semiconductors. In turn, the model developed for these devices may provide
      additional insights into proton conduction in biological systems.

PMID- 24089085
TI  - In situ grafting silica nanoparticles reinforced nanocomposite hydrogels.
AB  - Highly flexible nanocomposite hydrogels were prepared by using silica
      nanoparticles (SNPs) as fillers and multi-functional cross-links to graft
      hydrophilic poly(acrylic acid) (PAA) by free radical polymerization from an
      aqueous solution. The SNPs were collected by neighboring polymer chains and
      dispersed uniformly within a PAA matrix. The mechanical properties of the
      nanocomposite hydrogels were tailored by the concentration of SNPs according to
      the percolation model. It was proposed that covalent bonds of adsorbed chains on
      the filler surface resulted in the formation of a shell of an immobilized glassy
      layer and trapped entanglements, where the glassy polymer layer greatly enhanced
      the elastic modulus and the release of trapped entanglements at deformation
      contributed to the viscoelastic properties. 

PMID- 24089087
TI  - Combined in situ atomic force microscopy and infrared attenuated total reflection
      spectroelectrochemistry.
AB  - A novel analytical platform combining infrared attenuated total reflection (IR
      ATR) spectroelectrochemistry (SE) with atomic force microscopy (AFM) using a
      boron-doped diamond (BDD)-modified ATR crystal is presented. The utility of this
      combination is demonstrated investigating the electrodeposition of a polymer film
      via IR spectroscopy, while the surface modification is simultaneously imaged by
      AFM. The ATR waveguide consists of a single-crystal intrinsic diamond overgrown
      with a homoepitaxial BDD layer (thickness: ~100 nm, boron content: ~5 * 10(20)
      cm(-3)) to provide electric conductivity. The diamond ATR crystal is shaped in
      the form of a hemisphere with a beveled top and an octahedronal surface area of
      approximately 400 MUm(2). To demonstrate combined IR-ATR-SE-AFM measurements, the
      electro-polymerization of 3,4-ethylenedioxothiophene (EDOT) was selected as a
      model system. Depositions were obtained from aqueous solutions, while changes in
      IR signature, topography, and electrochemical behavior were recorded in situ and
      simultaneously during the polymerization process. 

PMID- 24089086
TI  - Boundaries of schizoaffective disorder: revisiting Kraepelin.
AB  - IMPORTANCE: Established nosology identifies schizoaffective disorder as a
      distinct category with boundaries separating it from mood disorders with
      psychosis and from schizophrenia. Alternative models argue for a single boundary
      distinguishing mood disorders with psychosis from schizophrenia (kraepelinian
      dichotomy) or a continuous spectrum from affective to nonaffective psychosis.
      OBJECTIVE: To identify natural boundaries within psychotic disorders by
      evaluating associations between symptom course and long-term outcome. DESIGN,
      SETTING, AND PARTICIPANTS: The Suffolk County Mental Health Project cohort
      consists of first-admission patients with psychosis recruited from all inpatient
      units of Suffolk County, New York (72% response rate). In an inception cohort
      design, participants were monitored closely for 4 years after admission, and
      their symptom course was charted for 526 individuals; 10-year outcome was
      obtained for 413. MAIN OUTCOMES AND MEASURES: Global Assessment of Functioning
      (GAF) and other consensus ratings of study psychiatrists. RESULTS: We used
      nonlinear modeling (locally weighted scatterplot smoothing and spline regression)
      to examine links between 4-year symptom variables (ratio of nonaffective
      psychosis to mood disturbance, duration of mania/hypomania, depression, and
      psychosis) and 10-year outcomes. Nonaffective psychosis ratio exhibited a sharp
      discontinuity-10 days or more of psychosis outside mood episodes predicted an 11
      point decrement in GAF-consistent with the kraepelinian dichotomy. Duration of
      mania/hypomania showed 2 discontinuities demarcating 3 groups: mania absent,
      episodic mania, and chronic mania (manic/hypomanic >1 year). The episodic group
      had a better outcome compared with the mania absent and chronic mania groups (12
      point and 8-point difference on GAF). Duration of depression and psychosis had
      linear associations with worse outcome. CONCLUSIONS AND RELEVANCE: Our data
      support the kraepelinian dichotomy, although the study requires replication. A
      boundary between schizoaffective disorder and schizophrenia was not observed,
      which casts further doubt on schizoaffective diagnosis. Co-occurring
      schizophrenia and mood disorder may be better coded as separate diagnoses, an
      approach that could simplify diagnosis, improve its reliability, and align it
      with the natural taxonomy.

PMID- 24089089
TI  - Impact of cold ischemia on cytokines after partial liver transplantation in rats.
AB  - To study the impact of cold ischemia on tumor necrosis factor-alpha (TNF-alpha)
      and interleukin-10 (IL-10) expression after liver transplantation, a stable model
      of partial liver transplantation in rats was established. The experimental
      animals were divided into the following groups: a partial hepatectomy control
      group, a group that received partial liver transplantation after 30 min of cold
      ischemia (experimental group A), and a group that received a partial liver
      transplantation after 10 h of cold ischemia (experimental group B). The survival
      rate was observed in each group. The liver tissue was sampled 1, 2, and 4 days
      after surgery, and immunohistochemical detection of proliferating cell nuclear
      antigen TNF-alpha and IL-10 was performed. The correlation between liver
      regeneration and TNF-alpha and IL-10 expression was analyzed, and the impact of
      the 2 cytokines on rat liver regeneration after liver transplantation was
      evaluated. The survival rates of rats in the partial hepatectomy control group,
      in the group that received a partial liver transplantation after 30 min of cold
      ischemia, and the group that received a partial liver transplantation after 10 h
      of cold ischemia were 100, 70, and 33.3%, respectively. The expression of
      proliferating cell nuclear antigen and TNF-alpha was decreased (P < 0.05), and IL
      10 expression was increased (P < 0.05) in animals that received a partial liver
      transplant after 10 h of cold ischemia compared with that in the animals that
      received a partial liver transplant after 30 min of cold ischemia. We conclude
      that with the extension of cold ischemic time, liver regeneration and survival
      rate after liver transplantation decreased. TNF-alpha and IL-10 play important
      regulatory roles in the regeneration process of transplanted livers. 

PMID- 24089088
TI  - Aberrant DNA methylation at genes associated with a stem cell-like phenotype in
      cholangiocarcinoma tumors.
AB  - Genetic abnormalities of cholangiocarcinoma have been widely studied; however,
      epigenomic changes related to cholangiocarcinogenesis have been less well
      characterized. We have profiled the DNA methylomes of 28 primary
      cholangiocarcinoma and six matched adjacent normal tissues using Infinium's
      HumanMethylation27 BeadChips with the aim of identifying gene sets aberrantly and
      epigenetically regulated in this tumor type. Using a linear model for microarray
      data, we identified 1610 differentially methylated autosomal CpG sites, with 809
      hypermethylated (representing 603 genes) and 801 hypomethylated (representing 712
      genes) in cholangiocarcinoma versus adjacent normal tissues (false-discovery rate
      <= 0.05). Gene ontology and gene set enrichment analyses identified gene sets
      significantly associated with hypermethylation at linked CpG sites in
      cholangiocarcinoma including homeobox genes and target genes of PRC2, EED, SUZ12,
      and histone H3 trimethylation at lysine 27. We confirmed frequent
      hypermethylation at the homeobox genes HOXA9 and HOXD9 by bisulfite
      pyrosequencing in a larger cohort of cholangiocarcinoma (n = 102). Our findings
      indicate a key role for hypermethylation of multiple CpG sites at genes
      associated with a stem cell-like phenotype as a common molecular aberration in
      cholangiocarcinoma. These data have implications for cholangiocarcinogenesis, as
      well as possible novel treatment options using histone methyltransferase
      inhibitors.

PMID- 24089090
TI  - Development of microsatellite markers for a hard-shelled mussel, Mytilus
      coruscus, and cross-species transfer.
AB  - The Korean mussel Mytilus coruscus, an endemic marine bivalve mollusk, is
      economically important. Its population is currently decreasing due to
      overexploitation and invasion of a more competitive species, Mytilus
      galloprovincialis. In this study, microsatellite markers for M. coruscus were
      developed using a cost-effective pyrosequencing technique. Among the 33,859
      dinucleotide microsatellite sequences identified, 176 loci that contained more
      than 8 CA, CT, or AT repeats were selected for primer synthesis. Sixty-four
      (36.4%) primer sets were produced from the 100- to 200-bp polymerase chain
      reaction products obtained from 2 M. coruscus individuals. Twenty of these were
      chosen to amplify DNA from 82 M. coruscus individuals, and 18 polymorphic loci
      and 2 monomorphic loci were selected as microsatellite markers. The number of
      alleles and the allele richness of the polymorphic loci ranged from 2 to 22 and
      from 2.0 to 19.7 with means of 10.8 and 10.1, respectively. Null alleles were
      detected for all but three loci, which resulted in an observed heterozygosity
      lower than the expected heterozygosity and therefore an excess of homozygotes. In
      a cross-species transfer analysis of these markers using 7 Mytilidae species, the
      locus Mc65 was amplified from all species tested and was found to be polymorphic
      in all of them. Among the species, M. galloprovincialis, Lithophaga curta, and
      Hormomya mutabilis showed the same transferability of 25%, but the five amplified
      loci were polymorphic only in M. galloprovincialis and H. mutabilis. These
      microsatellite markers may be useful for future resource management and
      artificial production of juveniles for aquaculture. 

PMID- 24089091
TI  - Morphological and molecular characteristics do not confirm popular classification
      of the Brazil nut tree in Acre, Brazil.
AB  - In the State of Acre, the Brazil nut tree, Bertholletia excelsa (Lecythidaceae),
      is classified by the local population into two types according to morphological
      characteristics, including color and quality of wood, shape of the trunk and
      crown, and fruit production. We examined the reliability of this classification
      by comparing morphological and molecular data of four populations of Brazil nut
      trees from Vale do Rio Acre in the Brazilian Amazon. For the morphological
      analysis, we evaluated qualitative and quantitative information of the trees,
      fruits, and seeds. The molecular analysis was performed using RAPD and ISSR
      markers, with cluster analysis. Significant differences were found between the
      two types of Brazil nut trees for the characters diameter at breast height, fruit
      yield, fruit size, and number of seeds per fruit. Despite the significant
      correlation between the morphological characteristics and the popular
      classification, we observed all possible combinations of morphological
      characteristics in both types of Brazil nut trees. In some individuals, the
      classification did not correspond to any of the characteristics. The results
      obtained with molecular markers showed that the two locally classified types of
      Brazil nut trees did not differ genetically, indicating that there is no
      consistent separation between them. 

PMID- 24089092
TI  - Novel splice variants of the bovine PCK1 gene.
AB  - Phosphoenolpyruvate carboxykinase 1 (PCK1), also named PEPCK-C, is a multiple
      function gene that is involved in gluconeogenesis, glyceroneogenesis,
      reproduction, female fertility, and development of obesity and diabetes. How its
      many functions are regulated was largely unknown. Therefore, we investigated mRNA
      expression and possible splice variants of PCK1 by screening cDNA in nine tissues
      from Holstein bulls and cows. PCK1 mRNA was highly expressed in the liver,
      kidney, ovary and testis; expression levels were low in the heart, spleen, and
      lung tissues. Expression of this gene was not detected in skeletal muscle. This
      led to the discovery of five novel bovine splice variants, named PCK1-AS1-PCK1
      AS5. In PCK1-AS1, 51 nucleotides in the interior of exon 2 were spliced out. In
      PCK1-AS2, exons 2 and 3 were altered by the alternative 3' and 5' splice sites,
      respectively. PCK1-AS3 was truncated from the 3' end of exon 2 to the 5' end of
      exon 4. In PCK1-AS4, exon 5 was completely spliced out. In PCK1-AS5, exons 5 and
      6 and the 5' end of exon 7 were spliced out. These splice variants (PCK1-AS1-PCK1
      AS5) potentially encoded shorter proteins (605, 546, 373, 246 and 274 amino
      acids, respectively), when compared to the complete protein (622 amino acids).
      Considering the functional domains of the PCK1 protein, it is likely that these
      splice variants considerably affect the function of this protein; alternative
      splicing could be one of the mechanisms by which the diverse functions of PCK1
      are regulated. 

PMID- 24089093
TI  - Comparison of factor-analytic and reduced rank models for test-day milk yield in
      Gyr dairy cattle (Bos indicus).
AB  - We analyzed 46,161 monthly test-day records of milk production from 7453 first
      lactations of crossbred dairy Gyr (Bos indicus) x Holstein cows. The following
      seven models were compared: standard multivariate model (M10), three reduced rank
      models fitting the first 2, 3, or 4 genetic principal components, and three
      models considering a 2-, 3-, or 4-factor structure for the genetic covariance
      matrix. Full rank residual covariance matrices were considered for all models.
      The model fitting the first two principal components (PC2) was the best according
      to the model selection criteria. Similar phenotypic, genetic, and residual
      variances were obtained with models M10 and PC2. The heritability estimates
      ranged from 0.14 to 0.21 and from 0.13 to 0.21 for models M10 and PC2,
      respectively. The genetic correlations obtained with model PC2 were slightly
      higher than those estimated with model M10. PC2 markedly reduced the number of
      parameters estimated and the time spent to reach convergence. We concluded that
      two principal components are sufficient to model the structure of genetic
      covariances between test-day milk yields. 

PMID- 24089094
TI  - Population structure and demographic history of Sicyopterus japonicus
      (Perciformes; Gobiidae) in Taiwan inferred from mitochondrial control region
      sequences.
AB  - The amphidromous goby Sicyopterus japonicus is distributed throughout southern
      Taiwan and Japan. Larvae of this freshwater fish go through a long marine stage.
      This migratory mode influences population genetic structure. We examined the
      genetic diversity, population differentiation, and demographic history of S.
      japonicus based on the mitochondrial DNA control region. We identified 102
      haplotypes from 107 S. japonicus individuals from 22 populations collected from
      Taiwan and Islet Lanyu. High mean haplotype diversity (h = 0.999) versus low
      nucleotide diversity (thetapi = 0.008) was detected across populations. There was
      low correspondence between clusters identified in the neighbor-joining tree and
      geographical region, as also indicated by AMOVA and pairwise F(ST) estimates.
      Both mismatch distribution analysis and Tajima's D test indicated that S.
      japonicus likely experienced a demographic expansion. Using a Bayesian skyline
      plot approach, we estimated the time of onset of the expansion of S. japonicus at
      135 kyr (during the Pleistocene) and the time of stable effective population size
      at approximately 2.5 kyr (last glacial maximum). Based on these results, we
      suggest 1) a panmictic population at the oceanic planktonic larval stage,
      mediated by the Kuroshio current; 2) a long planktonic marine stage and long
      period of dispersal, which may have permitted efficient tracking of environmental
      shifts during the Pleistocene; and 3) a stable, constant population size ever
      since the last glacial maximum.

PMID- 24089095
TI  - Identification of a novel human testicular interstitial gene, RNF148, and its
      expression regulated by histone deacetylases.
AB  - Multiple genes are restrictively expressed in mammalian testicular tissues, and
      they play important roles in the complex process of spermatogenesis.
      Investigation of these genes and their expression regulation mechanisms is
      valuable to elucidate the molecular process of spermatogenesis. In this study, we
      identified a novel human gene, ring finger protein 148 (RNF148) that is
      abundantly expressed in testes and slightly expressed in pancreas. In situ
      hybridization analysis showed that RNF148 messenger RNA was mainly present in the
      interstitial cells of human testicular tissues, and immunohistochemical analysis
      confirmed protein levels in that location. Treatment with histone deacetylase
      inhibitor trichostatin A activated the expression of RNF148 messenger RNA in a
      time- and concentration-dependent manner in HEK293T and HeLa cells, neither of
      which normally express RNF148. Chromatin immunoprecipitation analysis showed that
      trichostatin A treatment increased the binding of acetylated histone H3 to the
      RNF148 gene promoter. We identified a novel human testicular interstitial gene
      and observed that histone deacetylases regulate RNF148 expression. 

PMID- 24089096
TI  - Identification of a locus characteristic of male individuals of buffalo grass
      [Buchloe dactyloides (Nutt.) Engelm.] by using an RAPD marker.
AB  - Buffalo grass [Buchloe dactyloides (Nutt.) Engelm.] plants can be either male,
      female, or hermaphrodite (monoecious). As there is no morphological difference in
      the early vegetative growth of these three classes of plants, it is worthwhile to
      use molecular biological methods to attempt to identify the sex of a plant at
      this early growth period. In this study, we identified 23 plants that had a
      stable sex for over at least 3 years. Of these, 9 were male plants, 10 were
      female plants, and 4 were hermaphrodites. Screening of 300 RAPD primers
      identified a primer, namely S211 (5'-ttccccgcga-3'), which is capable of
      identifying male plants. The specific fragment was cloned, sequenced, and
      submitted to the GenBank database (accession No. JN982469). When used to identify
      the sex of 188 plants during their first growing season, the S211 primer
      correctly identified 85.8% of all male plants. Our results showed that the S211
      primer can identify the male, and in doing so, it facilitates buffalo grass
      breeding work. 

PMID- 24089097
TI  - DNA barcoding of populations of Fallopia multiflora, an indigenous herb in China.
AB  - Fallopia multiflora, locally known as Heshouwu, is one of the most important and
      widely used Chinese medicinal herbs. However, there is still considerable
      confusion concerning its different provenances. DNA barcoding is a recent aid to
      taxonomic identification and uses a short standardized DNA region to discriminate
      plant species. We assessed the applicability of 4 candidate DNA barcodes (matK,
      rbcL, psbA-trnH, and ITS2) to identify populations of F. multiflora. To our
      knowledge, this is the first attempt involving the plant kingdom to apply DNA
      barcoding at a level lower than species. Four DNA loci (matK, rbcL, psbA-trnH,
      and ITS2) of 105 samples, including the wild F. multiflora distributed in 17
      provinces of China and 4 cultivated F. multiflora lines, were amplified by PCR
      and sequenced. The 4 loci were evaluated by PCR amplification for sequence
      quality, extent of genetic divergence, DNA barcoding gap, and the ability to
      discriminate between populations by BLAST1 and Nearest Distance. We found that
      psbA-trnH was the best barcode, with significant inter-population variability and
      best potential for identifying F. multiflora. The combination of loci gave better
      performance for distinguishing populations than a single locus. We recommend
      using matK + rbcL + psbA-trnH + ITS2 or psbA-trnH alone for this species. This
      research demonstrates the utility of DNA barcoding for geoherbalism
      identifications. 

PMID- 24089098
TI  - Fast protocol for extraction of DNA from Prosopis spp leaves (plant adapted to
      arid environment) without liquid nitrogen.
AB  - The extraction of high-quality genomic DNA from Prosopis spp for polymerase chain
      reaction (PCR) amplification is complicated, owing to the presence of a high
      percentage of secondary metabolites that bind to or co-precipitate with nucleic
      acids. In the present study, we report a modified sodium dodecyl sulfate/phenol
      protocol that eliminates the use of liquid nitrogen in the maceration process,
      beta-mercaptoethanol in the buffer extraction, and the ethanol precipitation
      step. The A260/A280 absorbance ratios of the isolated DNA were approximately 2.0
      to 1.9, suggesting that the DNA fraction was pure and can be used for further PCR
      analysis. The DNA isolated by this protocol is of sufficient quality for
      molecular applications; this technique could be applied to other organisms that
      have similar substances that hinder DNA extraction. Finally, this proposal
      represents an alternative fast, cheap, and effective method for the isolation of
      genomic DNA from fresh leaves of Prosopis spp, even in low-technology
      laboratories.

PMID- 24089099
TI  - Molecular characterization of endophytes isolated from Saccharum spp based on
      esterase and ribosomal DNA (ITS1-5.8S-ITS2) analyses.
AB  - This study used esterases and ribosomal DNA (rDNA) markers to determine
      endophytic variability in order to better understand endophyte-host interactions.
      Polyacrylamide gel electrophoresis and esterase isoenzymes (EST; EC 3.1.1.3),
      with alpha-naphthyl acetate and beta-naphthyl acetate as substrates, were used to
      assess relationships among endophytes. ITS1-5.8S-ITS2 sequencing data were used
      as rDNA markers. Thirty-two esterases were obtained from 37 isolates of Saccharum
      spp, which clustered into five endophyte groups. Esterase EST-06 was observed
      with the highest frequency, being present in 22 of the 37 isolates analyzed,
      followed by esterase EST-11, which was present in 20 isolates. The esterases EST
      10 and EST-14 were present in 19 isolates and EST-09 was present in 18 isolates.
      The esterase EST-01 was unique to isolate 33 and can, therefore, be used as a
      marker for this isolate. None of the esterases identified were common to all
      isolates tested. Similarly, phylogenetic analysis, based on rDNA sequence data,
      classified the isolates into 5 genus groups: 1) Curvularia with a 100% bootstrap
      value (BP), 2) Alternaria with 100% BP, 3) Epicoccum with 60% BP, 4) Phoma with
      89% BP, and 5) Saccharicola with 100% BP. This polyphyletic analysis based on
      several markers, therefore, proved to be a valuable approach in determining the
      relationship between variation in endophytes and their associated host plants.
      Furthermore, both the esterase and rDNA analyses obtained similar results and
      were equally effective in resolving relationships. 

PMID- 24089100
TI  - The predictive validity of the aptitude test for the performance of students
      starting a medical curriculum.
AB  - INTRODUCTION: Selection of medical students varies between German- and French
      speaking Swiss faculties. Geneva introduced an aptitude test in 2010, aimed at
      helping decision making among students. The test was compulsory: it had to be
      taken by those who intended to register for medical studies. But it was not
      selective: there was no performance threshold under which registration would have
      been denied. METHODS: We followed 353 students who took the test in 2010, checked
      whether they confirmed their registration for medical studies and studied their
      performance during year 1 (selective year). RESULTS: The correlation between the
      aptitude test result and the academic performance during year 1 was 0.47 (n =
      191), and weakened to 0.38 (n = 214) when including repetition of year 1. The
      failure to pass in year 2 or success were associated with the aptitude test
      results (p <0.001). Overall, 20% of the students succeeded after one year, 26%
      after a repeated year 1, and 53% failed and could not follow further medical
      studies. CONCLUSION: Though there was a clear association between the aptitude
      test and academic performance, students did not appear to take into account when
      making their career decisions the ability of the test (as implemented in Geneva,
      that is, compulsory but not selective) to predict their future performance in the
      medical programme. The test was withdrawn after the 2012 session, but a number of
      issues regarding the medical selection procedure remain to be addressed.

PMID- 24089101
TI  - Competitive environments sustain costly altruism with negligible assortment of
      interactions.
AB  - Competition hinders the evolution of altruism amongst kin when beneficiaries gain
      at the expense of competing relatives. Altruism is consequently deemed to require
      stronger kin selection, or trait-selected synergies, or elastic population
      regulation, to counter this effect. Here we contest the view that competition
      puts any such demands on altruism. In ecologically realistic scenarios,
      competition influences both altruism and defection. We show how environments that
      pit defectors against each other allow strong altruism to evolve even in
      populations with negligible kin structure and no synergies. Competition amongst
      defectors presents relative advantages to altruism in the simplest games between
      altruists and defectors, and the most generic models of altruistic phenotypes or
      genotypes invading non-altruistic populations under inelastic density regulation.
      Given the widespread inevitability of competition, selection will often favour
      altruism because its alternatives provide lower fitness. Strong competition
      amongst defectors nevertheless undermines altruism, by facilitating invasion of
      unrelated beneficiaries as parasites. 

PMID- 24089102
TI  - Association between parental socioeconomic position and prevalence of asthma,
      atopic eczema and hay fever in children.
AB  - AIM: To determine the prevalence of asthma, atopic eczema and hay fever among
      children in different age groups and examine the associations with parental
      socioeconomic position. METHODS: A cross-sectional health survey of four complete
      birth-cohorts in the municipality of Copenhagen was conducted. Children aged 11
      and 15 years and parents of children aged 3 and 6 years completed questionnaires
      on symptoms and diseases. Data were linked to national registers on demographics
      and socioeconomic position measured as education, employment and income. In
      total, 9720 children/parents responded (50.5%). RESULTS: The prevalence of asthma
      and hay fever increased with increasing age; asthma: from 3.2% among children
      aged 3 years to 15.4% among children aged 15 years; hay fever: from 3.1% among
      children aged 3 years to 21.3% among children aged 15 years. The prevalence of
      atopic eczema did not vary with age and ranged between 15.5% and 17.8%. Odds
      Ratios for children of parents with the lowest vs. the highest educational level
      were 1.50 (95% CI = 1.17-1.91) for asthma; 1.68 (95% CI = 1.35-2.10) for hay
      fever; and 0.75 (95% CI = 0.64-0.89) for atopic eczema. Unemployment was
      significantly associated with a decreased risk of atopic eczema and eczema
      symptoms. There was no independent association between household income and any
      of the outcomes. CONCLUSIONS: The prevalence of asthma and hay fever, but not
      atopic eczema, increased with increasing age. Atopic eczema was associated with
      high parental educational level, whereas asthma and hay fever were associated
      with low educational level. No association with household income was found.

PMID- 24089103
TI  - Psychological distress and perceived health in inmates in Norwegian prisons.
AB  - BACKGROUND: Perceived health is a subjective measure of an individual's health
      based on self-reported, and self-knowledge about one's health status. It is
      related to one's functional status, morbidity, and mortality and serves as an
      important indicator in determining an individual's health status and health
      related quality of life. The main purpose of this study is to explore (i) how a
      sample of adult inmates perceived their health and (ii) identify factors that may
      be associated with their perceived health. METHODS: This was a cross-sectional
      study, where data collection involved the use of a structured questionnaire. The
      study sites were six prisons. A total of 144 inmates, 13 women (14%) and 131 men
      (91%) took part in the study. RESULTS: The odds of having perceived good health
      were reduced by increasing age of the inmate (OR = 0.94, 95% CI = 0.90-0.98) and
      increased by high level of education (OR = 4.11, 95% CI = 1.09-15.50) and long
      time spent in prison (OR = 3.56, 95% CI = 1.09-15.50), adjusting for ethnicity
      and a previous history of murder/manslaughter (p > .02). In the same adjusted
      analysis, the odds of perceived good health were decreased with medium high and
      high depressive score (OR = 0.06, 95% CI = 0.02-0.17 and OR = 0.06, 95% CI = 0.00
      0.48, respectively). CONCLUSIONS: Psychological distress, time spent in prison,
      level of education and age were independent predictors of perceived health. High
      levels of psychological distress predict poor perceived health. Low level of
      education predict poor perceived health, while time spent in prison and age
      predict good perceived health.

PMID- 24089107
TI  - Directed cell migration in multi-cue environments.
AB  - Cell migration plays a critical role in development, angiogenesis, immune
      response, wound healing and cancer metastasis. During these processes, cells are
      often directed to migrate towards targets by sensing aligned fibers or gradients
      in concentration, mechanical properties or electric field. Often times, cells
      must integrate migrational information from several of these different cues.
      While the cell migration behavior, signal transduction and cytoskeleton dynamics
      elicited by individual directional cues has been largely determined, responses to
      multiple directional cues are much less understood. However, initial work has
      pointed to several interesting behaviors in multi-cue environments, including
      competition and cooperation between cues to determine the migrational responses
      of cells. Much of the work on multi-cue sensing has been driven by the recent
      development of approaches to systematically and simultaneously control
      directional cues in vitro coupled with analysis and modeling that quantitatively
      describe those responses. In this review we present an overview of multi-cue
      directed migration with an emphasis on how cues compete or cooperate. We outline
      how multi-cue responses such as cue dominance might change depending on other
      environmental inputs. Finally, the challenges associated with the design of the
      environments to control multiple cues and the analysis and modeling of cell
      migration in multi-cue environments as well as some interesting biological
      questions associated with migration in complex environments are discussed.
      Understanding multi-cue migrational responses is critical to the mechanistic
      description of physiology and pathology, but also to the design of engineered
      tissues, where cell migration must be orchestrated to form specific tissue
      structures. 

PMID- 24089108
TI  - Identifying the bleeding trauma patient: predictive factors for massive
      transfusion in an Australasian trauma population.
AB  - BACKGROUND: Military and civilian data would suggest that hemostatic
      resuscitation results in improved outcomes for exsanguinating patients. However,
      identification of those patients who are at risk of significant hemorrhage is not
      clearly defined. We attempted to identify factors that would predict the need for
      massive transfusion (MT) in an Australasian trauma population, by comparing those
      trauma patients who did receive massive transfusion with those who did not.
      METHODS: Between 1985 and 2010, 1,686 trauma patients receiving at least 1 U of
      packed red blood cells were identified from our prospectively maintained trauma
      registry. Demographic, physiologic, laboratory, injury, and outcome variables
      were reviewed. Univariate analysis determined significant factors between those
      who received MT and those who did not. A predictive multivariate logistic
      regression model with backward conditional stepwise elimination was used for MT
      risk. Statistical analysis was performed using SPSS PASW. RESULTS: MT patients
      had a higher pulse rate, lower Glasgow Coma Scale (GCS) score, lower systolic
      blood pressure, lower hemoglobin level, higher Injury Severity Score (ISS),
      higher international normalized ratio (INR), and longer stay. Initial logistic
      regression identified base deficit (BD), INR, and hemoperitoneum at laparotomy as
      independent predictive variables. After assigning cutoff points of BD being
      greater than 5 and an INR of 1.5 or greater, a further model was created. A BD
      greater than 5 and either INR of 1.5 or greater or hemoperitoneum was associated
      with 51 times increase in MT risk (odds ratio, 51.6; 95% confidence interval,
      24.9-95.8). The area under the receiver operating characteristic curve for the
      model was 0.859. CONCLUSION: From this study, a combination of BD, INR, and
      hemoperitoneum has demonstrated good predictability for MT. This tool may assist
      in the determination of those patients who might benefit from hemostatic
      resuscitation. LEVEL OF EVIDENCE: Prognostic study, level III.

PMID- 24089109
TI  - The role of trauma team leaders in missed injuries: does specialty matter?
AB  - BACKGROUND: Previous studies have identified missed injuries as a common and
      potentially preventable occurrence in trauma care. Several patient- and injury
      related variables have been identified, which predict for missed injuries;
      however, differences in rate and severity of missed injuries between surgeon and
      nonsurgeon trauma team leaders (TTLs) have not previously been reported. METHODS:
      A retrospective review was conducted on a random sample of 10% of all trauma
      patients (Injury Severity Score [ISS] > 12) from 1999 to 2009 at a Canadian Level
      I trauma center. Missed injuries were defined as those identified greater than 24
      hours after presentation and were independently adjudicated by two reviewers.
      TTLs were identified as either surgeons or nonsurgeons. RESULTS: Of our total
      trauma population of 2,956 patients, 300 charts were randomly pulled for detailed
      review. Missed injuries occurred in 46 patients (15%). Most common missed
      injuries were fractures (n = 32, 70%) and thoracic injuries (n = 23, 50%). The
      majority of missed injuries resulted in minor morbidity with only 5 (11%)
      requiring operative intervention. On univariate analysis, higher ISS (p < 0.01),
      higher maximum Abbreviated Injury Scale (MAIS) score of the thorax (p < 0.01),
      and nonsurgeon TTL status were predictive of missed injuries (p = 0.02).
      Multivariable logistic regression revealed that, after adjustment for age, ISS,
      and severe head injuries, the presence of a nonsurgeon TTL was associated with an
      increased odds of missed injury (odds ratio, 2.15; 95% confidence interval, 1.10
      4.20). CONCLUSION: Missed injuries occurred in 15% of patients. A unique finding
      was the increased odds of missed injury with nonsurgeon TTLs. Further research
      should be undertaken to explore this relationship, elucidate potential causes,
      and propose interventions to narrow this discrepancy between TTL provider types.
      LEVEL OF EVIDENCE: Therapeutic study, level IV. Prognostic and epidemiologic
      study, level III.

PMID- 24089110
TI  - Emergency hernia repair in cirrhotic patients with ascites.
AB  - BACKGROUND: The optimal treatment for abdominal wall hernias in the setting of
      ascites is not clear. We describe our experience with emergent surgery for
      hernias in patients with cirrhosis and ascites and assess variables associated
      with poor short- and long-term outcomes to inform decisions about aggressive
      early repair. METHODS: We performed a retrospective review of all emergency
      abdominal wall hernia repairs admitted from the emergency department from January
      2000 to December 2011 in all patients with ascites caused by liver cirrhosis.
      Demographic data, comorbidities, complications, operative details, hospital
      length of stay, and admission model of end-stage liver disease (MELD) score was
      determined. Follow-up was detailed via comprehensive liver service electronic
      records. RESULTS: There were 69 emergent hernia surgeries in 68 patients during
      the study period. There were two early deaths (both MELD score> 20). Multivariate
      analysis revealed MELD score (18% increase in risk with each point of MELD),
      preoperative anemia (sevenfold increase in risk), and preoperative small bowel
      obstruction (ninefold increase in risk) as predictive factors of major
      complication. In patients with MELD score greater than 10, morbidity was more
      than 50%, and major morbidity is greater than 12% when MELD score is greater than
      20. CONCLUSION: Emergent hernia surgery in patients with ascites has low
      mortality but high morbidity and requires intense use of resources. To decrease
      the incidence of emergent hernia surgery, we recommend the aggressive use of
      elective repair. Emergent hernia repair, when necessary, should be performed at
      experienced centers and must include adequate ascites control with diuretic
      therapy and percutaneous paracentesis. Preoperative anemia and electrolyte
      abnormalities should be aggressively treated. Finally, while wound complications
      are common and frequently require reintervention, they are not associated with
      increased mortality. LEVEL OF EVIDENCE: Prognostic and epidemiologic study, level
      V.

PMID- 24089111
TI  - Delayed formation of splenic pseudoaneurysm following nonoperative management in
      blunt splenic injury: multi-institutional study in Osaka, Japan.
AB  - BACKGROUND: Delayed rupture is well-known as a severe complication after splenic
      injury treated with nonoperative management (NOM). The incidence and timing of
      splenic pseudoaneurysm (SPA) formation, which is a cause of delayed rupture
      following splenic injury, have not been thoroughly investigated, and the timing
      of follow-up computed tomography (CT) is controversial. The objective of this
      study was to clarify the incidence and timing of both the delayed formation and
      spontaneous resolution of SPA following splenic injuries treated with NOM in
      several trauma centers in Japan. METHODS: This was a retrospective review of all
      patients with documented blunt splenic injury who were treated with NOM from 2003
      through 2010 in five trauma and critical care centers. RESULTS: The present study
      consisted of 104 patients, including 16 patients (15.4%) with delayed formation
      of SPA (7 patients with Grade II and 9 with Grade III) during their clinical
      course. SPA was diagnosed with enhanced CT at a mean (SD) of 4.6 (2.1) hospital
      days (range, 1-8 days) after admission. Delayed formation of SPA was found in
      30.4% of Grade II injuries and in 18.4% of Grade III injuries. Eight patients
      with delayed formation of SPA were observed without transcatheter arterial
      embolization during their entire stay. These SPAs were spontaneously occluded on
      follow-up enhanced CT or angiography. Spontaneous occlusion of SPA was confirmed
      at 5.2 (2.6) hospital days (range, 2-10 days) after diagnosis of delayed SPA.
      CONCLUSION: Delayed formation of SPAs was recognized with enhanced helical CT in
      15% of all patients during hospital Days 1 to 8. About one half of the SPAs had
      occluded spontaneously without therapeutic intervention. Our results suggested
      that follow-up enhanced CT performed approximately 1 week after splenic injury
      may be useful to detect delayed SPA formation. LEVEL OF EVIDENCE: Epidemiologic
      study, level III.

PMID- 24089112
TI  - Benchmarking the incidence of organ failure after injury at trauma centers and
      nontrauma centers in the United States.
AB  - BACKGROUND: Organ failure after injury is a significant cause of morbidity and
      mortality, yet its true incidence is unknown. We sought to benchmark the
      incidence of organ failure following injury at trauma centers and nontrauma
      centers using a nationally representative sample of hospital discharges. We
      hypothesized that injured patients receiving care at trauma centers would have a
      lower incidence of organ failure than those at nontrauma centers. METHODS: We
      used the 2006 Nationwide Inpatient Sample to identify injured adults (age >= 15
      years) with organ dysfunction using specific DRG International Classification of
      Diseases-9th Rev. codes by system. After adjusting for hospital size, geographic
      region, comorbidities, Injury Severity Score (ISS), age, and sex, a multivariate
      logistic regression model was created to compare rates of organ dysfunction
      between trauma centers and nontrauma centers. RESULTS: We identified 396,276
      injured patients, representing the patient care experience of a total of
      1,939,473 patients. Among these patients, 6.5% had concurrent organ failure.
      Injured patients who had acute organ failure were more likely to die than injured
      patients without organ failure (12.4% vs. 1.7%, p < 0.001). Mortality increased
      with the number of organ system failures. Patients treated at trauma centers had
      a higher incidence of respiratory and cardiac failure compared with nontrauma
      centers. CONCLUSION: We offer the first national benchmark of rates of acute
      organ failure among injured patients. Postinjury organ failure is uncommon, but
      incidence increases with injury severity and correlates with mortality. Patients
      at trauma centers had higher rates of respiratory and cardiac failure, possibly
      representing differences in referral patterns or resuscitation strategies. LEVEL
      OF EVIDENCE: Prognostic and epidemiologic study, level III.

PMID- 24089113
TI  - Acute kidney injury is surprisingly common and a powerful predictor of mortality
      in surgical sepsis.
AB  - BACKGROUND: Acute kidney injury (AKI) is a common and often catastrophic
      complication in hospitalized patients; however, the impact of AKI in surgical
      sepsis remains unknown. We used Risk, Injury, Failure, Loss, End stage (RIFLE)
      consensus criteria to define the incidence of AKI in surgical sepsis and
      characterize the impact of AKI on patient morbidity and mortality. METHODS: Our
      prospective, institutional review board-approved sepsis research database was
      retrospectively queried for the incidence of AKI by RIFLE criteria, excluding
      those with chronic kidney disease. Patients were grouped into sepsis, severe
      sepsis, and septic shock by refined consensus criteria. Data including
      demographics, baseline biomarkers of organ dysfunction, and outcomes were
      compared by Student's t test and chi test. Multivariable regression analysis was
      performed for the effect of AKI on mortality adjusting for age, sex, African
      American race, elective surgery, Acute Physiology and Chronic Health Evaluation
      II score, septic shock versus severe sepsis, and sepsis source. RESULTS: During
      the 36-month study period ending on December 2010, 246 patients treated for
      surgical sepsis were evaluated. AKI occurred in 67% of all patients, and 59%,
      60%, and 88% of patients had sepsis, surgical sepsis, and septic shock,
      respectively. AKI was associated with Hispanic ethnicity, several baseline
      biomarkers of organ dysfunction, and a greater severity of illness. Patients with
      AKI had fewer ventilator-free and intensive care unit-free days and a decreased
      likelihood of discharge to home. Morbidity and mortality increased with severity
      of AKI, and AKI of any severity was found to be a strong predictor of hospital
      mortality (odds ratio, 10.59; 95% confidence interval, 1.28-87.35; p = 0.03) in
      surgical sepsis. CONCLUSION: AKI frequently complicates surgical sepsis, and
      serves as a powerful predictor of hospital mortality in severe sepsis and septic
      shock. LEVEL OF EVIDENCE: Prognostic and epidemiologic study, level III.

PMID- 24089114
TI  - Predictors of survival and neurologic outcomes in children with traumatic out-of
      hospital cardiac arrest during the early postresuscitative period.
AB  - BACKGROUND: The outcome of children with traumatic out-of-hospital cardiac arrest
      (OHCA) is poor, and the information regarding survival in the postresuscitative
      period is limited. The aim of this study was to determine the clinical features
      during the early postresuscitative period that may predict survival or neurologic
      outcomes in children with traumatic OHCA. METHODS: Information on 362 children
      (<19 years) who presented to the emergency departments of three medical centers
      and experienced traumatic OHCA during the study period (January 2003 to December
      2010) were retrospectively included. The postresuscitative clinical features
      during the early postresuscitative period, defined as the first hour after
      achieving sustained return of spontaneous circulation, which correlated with
      survival and neurologic outcomes were analyzed. RESULTS: Among 152 children (42%)
      who achieved sustained return of spontaneous circulation, 34 (9.4%) survived to
      discharge, and 11 (3%) had good neurologic outcomes (Pediatric Cerebral
      Performance Category Scale, 1 or 2). Early postresuscitative clinical features,
      which reflected initial cardiac output and end-organ perfusion, can predict the
      chance of survival. Such features included the following: high or normal blood
      pressure, normal heart rate, sinus rhythm, urine output of more than 1 mL/kg per
      hour, and noncyanotic skin color (all p < 0.05). Initial Glasgow Coma Scale (GCS)
      score of greater than 7 predicted a good neurologic outcome in survivors (p =
      0.008). CONCLUSION: Predictors of survival were high or normal blood pressure,
      normal heart rate, sinus rhythm, urine output of more than 1 mL/kg per hour, and
      noncyanotic skin color. Most importantly, initial GCS score of greater than 7
      predicted a good neurologic outcome in survivors. LEVEL OF EVIDENCE: Prognostic
      study, level III.

PMID- 24089115
TI  - Sternal fracture: isolated lesion versus polytrauma from associated extrasternal
      injuries--analysis of 1,867 cases.
AB  - BACKGROUND: Sternal fractures fall into two distinct categories as follows: (1)
      isolated sternal fracture (ISF) without associated injury and (2) polytrauma
      sternal fracture (PSF) with associated extrasternal injury. PSF can be
      sufficiently severe to require hospitalization, while ISF is usually a mild
      insult manageable in an ambulatory setting. Nonetheless, most patients with ISF
      are hospitalized. The disconnect between treatment based on existing evidence and
      actual clinical practice may be caused in large part by the small patient cohorts
      in published studies conducive to inaccurate conclusions. This article addresses
      the issue by analyzing prospectively collected data on a far larger population
      than hitherto available. METHODS: The Israeli National Trauma Registry (INTR)
      collects data prospectively on patients admitted to trauma centers in Israel. We
      analyzed the INTR database on sternal fractures for demographics, mechanisms and
      severity of injury, diagnostic evaluation, treatment, and outcomes. RESULTS:
      Between 1997 and 2008, the INTR received data on 1,867 consecutive patients
      hospitalized with sternal fractures. The injury was sustained most often during
      motor vehicle accidents (84.1%), followed by falls (10.3%) and other blunt or
      penetrating mechanisms (5.6%). ISF was sustained in 26.4%, and PSF was sustained
      in 73.6%. Associated injuries involved most parts of the body. Cardiac contusions
      or lacerations were diagnosed in 1.8% of the 1,867 patients. ISF was associated
      with a lower incidence of cardiorespiratory compromise, more favorable trauma
      scores (Glasgow Coma Scale [GCS] score > 14, Revised Trauma Score > 11), and use
      of fewer intensive care facilities or operations compared with PSF. Endotracheal
      intubation, chest tube insertion, or thoracotomy was not performed in any ISF
      patient but was performed in 16.9% of the PSF cohort. The differences between ISF
      and PSF were statistically significant in all analyzed indices of injury
      severity. CONCLUSION: This study produced compelling evidence that ISF is an
      identifiable and mild injury. Consequently, pain, the major clinical
      manifestation of ISF, can usually be treated in outpatient settings. To avoid the
      inconvenience, risk of complications, and cost associated with hospitalization,
      discharge from the emergency department merits serious consideration. LEVEL OF
      EVIDENCE: Prognostic and epidemiologic study, level II.

PMID- 24089116
TI  - Trends in the treatment for traumatic central cord syndrome without bone injury
      in the United States from 2000 to 2009.
AB  - BACKGROUND: Treatment for traumatic central cord syndrome (TCCS) without bone
      injury is still controversial. The purpose of this study was to examine trends in
      the treatment for TCCS without bone injury in the United States. METHODS:
      Clinical data were obtained from the US Nationwide Inpatient Sample from 2000 to
      2009. Patients with TCCS without bone injury were identified and divided into
      those receiving surgical treatment and those receiving conservative treatment
      according to the International Classification of Diseases-9th Rev.-Clinical
      Modification codes. Patient and health care system-related demographic data were
      retrieved. Trends in the treatment and patient outcomes were analyzed.
      Multivariate logistic regression analysis was then performed to identify the
      predictors for surgical treatment. RESULTS: The ratio of patients who underwent
      surgical treatment was 27.1%. This ratio increased from 14.8% in 2000 to 30.5% in
      2009 (p = 0.008). A total of 47.2% of surgical procedures were performed between
      Days 0 and 2. Multivariate analysis revealed that larger hospital size was a
      significant predictor for surgical treatment and patients who received treatment
      in Northeastern region were less likely to undergo surgical treatment.
      Comparisons between patients receiving surgical and conservative treatment
      revealed that those receiving surgical treatment had significantly higher overall
      in-hospital complication rate (18.6% vs. 14.5%), lower pulmonary embolism rate
      (0.5% vs. 1.2%), lower in-hospital mortality rate (2.0% vs. 2.7%), longer
      hospital stays (11.2 days vs. 9.9 days), and increased total hospital costs
      ($93,940 vs. $50,701). CONCLUSION: The ratio of patients who underwent surgical
      treatment for TCCS without bone injury increased from 2000 to 2009. Approximately
      half of surgical procedures were performed from Days 0 to 2. Patients who
      received treatment in a small hospital or the Northeastern region were less
      likely to undergo surgical treatment. Although the overall in-hospital
      complication rate was higher in patients with surgical treatment, pulmonary
      embolism and in-hospital mortality rates were higher in patients with
      conservative treatment than those in patients with surgical treatment. LEVEL OF
      EVIDENCE: Prognostic and epidemiologic study, level III. Therapeutic study, level
      IV.

PMID- 24089117
TI  - Withholding and termination of resuscitation of adult cardiopulmonary arrest
      secondary to trauma: resource document to the joint NAEMSP-ACSCOT position
      statements.
AB  - In the setting of traumatic cardiopulmonary arrest, protocols that direct
      emergency medical service (EMS) providers to withhold or terminate resuscitation,
      when clinically indicated, have the potential to decrease unnecessary use of
      warning lights and sirens and save valuable public health resources. Protocols to
      withhold resuscitation should be based on the determination that there are no
      obvious signs of life, the injuries are obviously incompatible with life, there
      is evidence of prolonged arrest, and there is a lack of organized
      electrocardiographic activity. Termination of resuscitation is indicated when
      there are no signs of life and no return of spontaneous circulation despite
      appropriate field EMS treatment that includes minimally interrupted
      cardiopulmonary resuscitation. Further research is needed to determine the
      appropriate duration of cardiopulmonary resuscitation before termination of
      resuscitation and the proper role of direct medical oversight in termination of
      resuscitation protocols. This article is the resource document to the position
      statements, jointly endorsed by the National Association of EMS Physicians and
      the American College of Surgeons' Committee on Trauma, on withholding and
      termination of resuscitation in traumatic cardiopulmonary arrest. 

PMID- 24089119
TI  - The effect of suturing on force for dislodgement of tracheostomy tubes: medial
      versus lateral sutures.

PMID- 24089118
TI  - Anticoagulant and antiplatelet medications encountered in emergency surgery
      patients: a review of reversal strategies.

PMID- 24089120
TI  - Autonomic dysreflexia: a clinical emergency.

PMID- 24089121
TI  - A clinical series of resuscitative endovascular balloon occlusion of the aorta
      for hemorrhage control and resuscitation.
AB  - BACKGROUND: A requirement for improved methods of hemorrhage control and
      resuscitation along with the translation of endovascular specialty skills has
      resulted in reappraisal of resuscitative endovascular balloon occlusion of the
      aorta (REBOA) for end-stage shock. The objective of this report was to describe
      implementation of REBOA in civilian trauma centers. METHODS: Descriptive case
      series of REBOA (December 2012 to March 2013) used in scenarios of end-stage
      hemorrhagic shock at the University of Maryland, R. Adams Cowley Shock Trauma
      Center, Baltimore, Maryland, and Herman Memorial Hospital, The Texas Trauma
      Institute, Houston, Texas. RESULTS: REBOA was performed by trauma and acute care
      surgeons for blunt (n = 4) and penetrating (n = 2) mechanisms. Three cases were
      REBOA in the descending thoracic aorta (Zone I) and three in the infrarenal aorta
      (Zone III). Mean (SD) systolic blood pressure at the time of REBOA was 59 (27) mm
      Hg, and mean (SD) base deficit was 13 (5). Arterial access was accomplished using
      both direct cutdown (n = 3) and percutaneous (n = 3) access to the common femoral
      artery. REBOA resulted in a mean (SD) increase in blood pressure of 55 (20) mm
      Hg, and the mean (SD) aortic occlusion time was 18 (34) minutes. There were no
      REBOA-related complications, and there was no hemorrhage-related mortality.
      CONCLUSION: REBOA is a feasible and effective means of proactive aortic control
      for patients in end-stage shock from blunt and penetrating mechanisms. With
      available technology, this method of resuscitation can be performed by trauma and
      acute care surgeons who have benefited from instruction on a limited endovascular
      skill set. Future work should be aimed at devices that allow easy, fluoroscopy
      free access and studies to define patients most likely to benefit from this
      procedure. LEVEL OF EVIDENCE: Therapeutic study, level V.

PMID- 24089122
TI  - Toward medical dystopia.

PMID- 24089123
TI  - Frederic E.B. Foley: beyond the catheter.

PMID- 24089125
TI  - Ben Eiseman, MD (1917-2012).

PMID- 24089126
TI  - Traumatic abdominal wall hernia classification.

PMID- 24089127
TI  - Re: Traumatic abdominal wall hernia classifications.

PMID- 24089128
TI  - Hyperacute adrenal insufficiency after hemorrhagic shock: facts and fiction.

PMID- 24089129
TI  - Re: Hyperacute adrenal insufficiency after hemorrhagic shock: Facts and fiction.

PMID- 24089130
TI  - Timing of tracheostomy after anterior cervical spine fixation.

PMID- 24089131
TI  - Re: timing of tracheostomy after anterior cervical spine fixation.

PMID- 24089133
TI  - Treatment and cosmetic outcome of superpulsed CO2 laser for basal cell carcinoma.
AB  - INTRODUCTION: There are many different treatments for basal cell carcinoma, but
      the most common is surgical excision. CO2 laser could be an alternative treatment
      for many situations in which other treatments are not possible or available.
      METHODS: This follow-up study was performed on 74 (40 female and 34 male)
      patients with a total of 113 basal cell carcinoma lesions that were
      pathologically documented. First, the tumor mass was debulked by curettage and
      later 2 to 5 mm of marginal skin and the debulked area were subjected to 2 to 4
      passes of pulsed CO2 laser. RESULTS: Out of 113 lesions, the nodular type
      accounted for 67 (59.3%) lesions, and 40 (35.4%) lesions were seen in the nasal
      area as the most common clinical subtype and site of involvement. One hundred six
      lesions (93.7%) of basal cell carcinoma showed a cure after one session. Good to
      excellent cosmetic outcomes were seen in 97 (85.8%) cases. CONCLUSION: This
      method appears to be an appropriate alternative treatment for basal cell
      carcinoma lesions that are smaller than 2 cm, superficial, and pigmented, and
      have a nodular clinical subtype without an aggressive pathologic pattern. This
      method should be used with caution in the nasal area with lesions larger than 2
      cm.

PMID- 24089134
TI  - ABO blood groups, Rhesus factor, and Behcet's disease.
AB  - INTRODUCTION: Recently, numerous studies have been carried out to explain the
      genetics and immunopathogenesis of Behcet's disease (BD). There is still
      insufficient understanding of its etiopathogenesis, but substantial genetic and
      immune system abnormalities have been suggested. Several studies have shown
      remarkable associations of ABO blood groups with various diseases. This study
      investigated the relationship between ABO and Rhesus (D) blood groups and
      Behcet's disease in Turkish patients. METHODS: Clinical data on gender, ABO, and
      Rhesus blood type of patients with BD were collected at the Kayseri Education and
      Research Hospital from 2005 to 2012. A total of 115 patients with BD were
      assessed for their association with ABO or Rhesus (D) blood groups and compared
      with the distribution of the blood groups of 25,701 healthy donors admitted to
      the Kayseri Education and Research Hospital Blood Center in 2010 and 2011.
      RESULTS: The distribution of ABO and Rhesus blood groups in patients with BD was
      similar to the healthy donors. No relationship was found between ABO or Rhesus
      blood groups and BD at our hospital. CONCLUSION: Further studies with a larger
      series and in different centers may be valuable for identifying the association
      between ABO or Rhesus (D) blood groups and BD.

PMID- 24089135
TI  - Vaccination indications and limits in the elderly.
AB  - Infections are a major cause of morbidity and mortality in the elderly. Although
      vaccination is crucial for preventing infectious diseases, the ability of the
      elderly to establish an effective immune response to vaccination is much lower
      compared to the younger population. In most industrialized countries, four
      vaccines are now recommended for people over 60 years of age: influenza vaccine,
      pneumococcal vaccine, herpes zoster vaccine, and a vaccine combining tetanus
      toxoid, reduced diphtheria toxoid, and acellular pertussis. Only the last vaccine
      provides an adequate antibody response. The influenza and pneumococcal vaccines
      seem to be able to alleviate disease. The herpes zoster vaccine somewhat prevents
      reactivation of herpes zoster and decreases the severity of postherpetic
      neuralgia. Recent technological advances and novel adjuvants are providing new
      opportunities for improving vaccination of the elderly. Lifelong vaccination
      schedules should be promoted in order to achieve the herd immunity threshold.
      Maintaining the health of the population requires moving from a childhood-based
      vaccination strategy to a more balanced vaccination program throughout life. 

PMID- 24089136
TI  - Disseminated scar sarcoidosis may predict pulmonary involvement in sarcoidosis.
AB  - Sarcoidosis is a chronic, inflammatory, multi-organ disease of unknown origin
      that is characterized by non-caseating granuloma formation in affected organs.
      Cutaneous involvement is reported in 25% of patients with sarcoidosis. Scar
      sarcoidosis is rare but is clinically specific for skin sarcoidosis. Systemic
      involvement is seen in most patients with scar sarcoidosis. We present a case of
      scar sarcoidosis in a 30-year-old male that developed infiltrated nodules on old
      scars, including on his penile shaft, which is rare, and that also had pulmonary
      involvement. Scar sarcoidosis should be considered in the differential diagnosis
      of changes in all scar areas and should be investigated for systemic involvement.

PMID- 24089137
TI  - Acquired zinc deficiency: a case report.
AB  - Zinc deficiency can be an autosomal recessive inherited or acquired disorder and
      is classically characterized by acral and periorificial dermatitis, alopecia, and
      diarrhea. We report a case of acquired zinc deficiency in a premature 6-week-old
      boy with typical skin manifestation of zinc deficiency and decreased plasma zinc
      level. After starting zinc replacement therapy, the skin lesions completely
      disappeared in the first few weeks. 

PMID- 24089138
TI  - Cobalt phosphate-modified barium-doped tantalum nitride nanorod photoanode with
      1.5% solar energy conversion efficiency.
AB  - Spurred by the decreased availability of fossil fuels and global warming, the
      idea of converting solar energy into clean fuels has been widely recognized.
      Hydrogen produced by photoelectrochemical water splitting using sunlight could
      provide a carbon dioxide lean fuel as an alternative to fossil fuels. A major
      challenge in photoelectrochemical water splitting is to develop an efficient
      photoanode that can stably oxidize water into oxygen. Here we report an efficient
      and stable photoanode that couples an active barium-doped tantalum nitride
      nanostructure with a stable cobalt phosphate co-catalyst. The effect of barium
      doping on the photoelectrochemical activity of the photoanode is investigated.
      The photoanode yields a maximum solar energy conversion efficiency of 1.5%, which
      is more than three times higher than that of state-of-the-art single-photon
      photoanodes. Further, stoichiometric oxygen and hydrogen are stably produced on
      the photoanode and the counter electrode with Faraday efficiency of almost unity
      for 100 min. 

PMID- 24089139
TI  - Knockdown of beta-catenin with dicer-substrate siRNAs reduces liver tumor burden
      in vivo.
AB  - Despite progress in identifying molecular drivers of cancer, it has been
      difficult to translate this knowledge into new therapies, because many of the
      causal proteins cannot be inhibited by conventional small molecule therapeutics.
      RNA interference (RNAi), which uses small RNAs to inhibit gene expression,
      provides a promising alternative to reach traditionally undruggable protein
      targets by shutting off their expression at the messenger RNA (mRNA) level.
      Challenges for realizing the potential of RNAi have included identifying the
      appropriate genes to target and achieving sufficient knockdown in tumors. We have
      developed high-potency Dicer-substrate short-interfering RNAs (DsiRNAs) targeting
      beta-catenin and delivered these in vivo using lipid nanoparticles, resulting in
      significant reduction of beta-catenin expression in liver cancer models.
      Reduction of beta-catenin strongly reduced tumor burden, alone or in combination
      with sorafenib and as effectively as DsiRNAs that target mitotic genes such as
      PLK1 and KIF11. beta-catenin knockdown also strongly reduced the expression of
      beta-catenin-regulated genes, including MYC, providing a potential mechanism for
      tumor inhibition. These results validate beta-catenin as a target for liver
      cancer therapy and demonstrate the promise of RNAi in general and DsiRNAs in
      particular for reaching traditionally undruggable cancer targets. 

PMID- 24089140
TI  - Overexpressing sonic hedgehog peptide restores periosteal bone formation in a
      murine bone allograft transplantation model.
AB  - Although activation of hedgehog (Hh) signaling has been shown to induce
      osteogenic differentiation in vitro and bone formation in vivo, the underlying
      mechanisms and the potential use of Hh-activated mesenchymal progenitors in bone
      defect repair remain elusive. In this study, we demonstrated that implantation of
      periosteal-derived mesenchymal progenitor cells (PDMPCs) that overexpressed an N
      terminal sonic hedgehog peptide (ShhN) via an adenoviral vector (Ad-ShhN)
      restored periosteal bone collar formation in a 4-mm segmental bone allograft
      model in immunodeficient mice. Ad-ShhN enhanced donor cell survival and
      microvessel formation in collagen scaffold at 2 weeks after surgery and induced
      donor cell-dependent bone formation at 6 weeks after surgery. Fluorescence
      activated cell sorting analysis further showed that Ad-ShhN-PDMPC-seeded scaffold
      contained a twofold more CD45(-)Sca-1(+)CD34(+)VEGFR2(+) endothelial progenitors
      than Ad-LacZ-PDMPC-seeded scaffold at day 7 after surgery. Ad-ShhN-transduced
      PDMPCs induced a 1.8-fold more CD31(+) microvessel formation than Ad-LacZ
      transduced PDMPCs in a coculture of endothelial progenitors and PDMPCs. Taken
      together, our data show that overexpression of ShhN in mesenchymal progenitors
      improves bone defect reconstruction by enhancing donor progenitor cell survival,
      differentiation, and scaffold revascularization at the site of compromised
      periosteum. Hh agonist-based therapy, therefore, merits further investigation in
      tissue engineering-based applications aimed at enhancing bone defect repair and
      reconstruction. 

PMID- 24089141
TI  - DNA intermediates of meiotic recombination in synchronous S. pombe at optimal
      temperature.
AB  - Crossovers formed by recombination between homologous chromosomes are important
      for proper homolog segregation during meiosis and for generation of genetic
      diversity. Optimal molecular analysis of DNA intermediates of recombination
      requires synchronous cultures. We previously described a mutant, pat1-as2, of the
      fission yeast Schizosaccharomyces pombe that undergoes synchronous meiosis at 25
      degrees C when an ATP analog is added to the culture. Here, we compare
      recombination intermediates in pat1-as2 at 25 degrees C with those in the widely
      used pat1-114 temperature-sensitive mutant at 34 degrees C, a temperature higher
      than optimal. DNA double-strand breaks at most hotspots are similarly abundant in
      the two conditions but, remarkably, a few hotspots are distinctly deficient at 25
      degrees C. In both conditions, Holliday junctions at DNA break hotspots form more
      frequently between sister chromatids than between homologs, but a novel species,
      perhaps arising from invasion by only one end of broken DNA, is more readily
      observed at 25 degrees C. Our results confirm the validity of previous assays of
      recombination intermediates in S. pombe and provide new information on the
      mechanism of meiotic recombination. 

PMID- 24089143
TI  - Malaria parasites utilize both homologous recombination and alternative end
      joining pathways to maintain genome integrity.
AB  - Malaria parasites replicate asexually within their mammalian hosts as haploid
      cells and are subject to DNA damage from the immune response and chemotherapeutic
      agents that can significantly disrupt genomic integrity. Examination of the
      annotated genome of the parasite Plasmodium falciparum identified genes encoding
      core proteins required for the homologous recombination (HR) pathway for
      repairing DNA double-strand breaks (DSBs), but surprisingly none of the
      components of the canonical non-homologous end joining (C-NHEJ) pathway were
      identified. To better understand how malaria parasites repair DSBs and maintain
      genome integrity, we modified the yeast I-SceI endonuclease system to generate
      inducible, site-specific DSBs within the parasite's genome. Analysis of repaired
      genomic DNA showed that parasites possess both a typical HR pathway resulting in
      gene conversion events as well as an end joining (EJ) pathway for repair of DSBs
      when no homologous sequence is available. The products of EJ were limited in
      number and identical products were observed in multiple independent experiments.
      The repair junctions frequently contained short insertions also found in the
      surrounding sequences, suggesting the possibility of a templated repair process.
      We propose that an alternative end-joining pathway rather than C-NHEJ, serves as
      a primary method for repairing DSBs in malaria parasites. 

PMID- 24089142
TI  - The dynamics of genome replication using deep sequencing.
AB  - Eukaryotic genomes are replicated from multiple DNA replication origins. We
      present complementary deep sequencing approaches to measure origin location and
      activity in Saccharomyces cerevisiae. Measuring the increase in DNA copy number
      during a synchronous S-phase allowed the precise determination of genome
      replication. To map origin locations, replication forks were stalled close to
      their initiation sites; therefore, copy number enrichment was limited to origins.
      Replication timing profiles were generated from asynchronous cultures using
      fluorescence-activated cell sorting. Applying this technique we show that the
      replication profiles of haploid and diploid cells are indistinguishable,
      indicating that both cell types use the same cohort of origins with the same
      activities. Finally, increasing sequencing depth allowed the direct measure of
      replication dynamics from an exponentially growing culture. This is the first
      time this approach, called marker frequency analysis, has been successfully
      applied to a eukaryote. These data provide a high-resolution resource and
      methodological framework for studying genome biology. 

PMID- 24089144
TI  - Higher-order chromatin domains link eQTLs with the expression of far-away genes.
AB  - Distal expression quantitative trait loci (distal eQTLs) are genetic mutations
      that affect the expression of genes genomically far away. However, the mechanisms
      that cause a distal eQTL to modulate gene expression are not yet clear. Recent
      high-resolution chromosome conformation capture experiments along with a growing
      database of eQTLs provide an opportunity to understand the spatial mechanisms
      influencing distal eQTL associations on a genome-wide scale. We test the
      hypothesis that spatial proximity contributes to eQTL-gene regulation in the
      context of the higher-order domain structure of chromatin as determined from
      recent Hi-C chromosome conformation experiments. This analysis suggests that the
      large-scale topology of chromatin is coupled with eQTL associations by providing
      evidence that eQTLs are in general spatially close to their target genes, occur
      often around topological domain boundaries and preferentially associate with
      genes across domains. We also find that within-domain eQTLs that overlap with
      regulatory elements such as promoters and enhancers are spatially more close than
      the overall set of within-domain eQTLs, suggesting that spatial proximity derived
      from the domain structure in chromatin plays an important role in the regulation
      of gene expression. 

PMID- 24089147
TI  - Power generation from water flowing through three-dimensional graphene foam.
AB  - Three-dimensional graphene foam (GF) is synthesized by CVD. When water flows
      through GF, electricity is induced. The direction of the induced current is
      dominated by the flow direction of water; the value of induced current is related
      to the flow velocity but has no relationship with the flow direction and external
      bias voltage. 

PMID- 24089146
TI  - Electrospun nanofibers and multi-responsive supramolecular assemblies constructed
      from a pillar[5]arene-based receptor.
AB  - Multi-responsive supramolecular polymers have been constructed from
      pillar[5]arene-based receptors. Significantly, nanofibers, nanosized
      supramolecular polymers based on pillararenes, have been successfully fabricated
      employing an electrospinning technique for the first time. 

PMID- 24089145
TI  - Interplay between the trigger loop and the F loop during RNA polymerase
      catalysis.
AB  - The trigger loop (TL) in the RNA polymerase (RNAP) active center plays key roles
      in the reactions of nucleotide addition and RNA cleavage catalyzed by RNAP. The
      adjacent F loop (FL) was proposed to contribute to RNAP catalysis by modulating
      structural changes in the TL. Here, we investigate the interplay between these
      two elements during transcription by bacterial RNAP. Thermodynamic analysis of
      catalysis by RNAP variants with mutations in the TL and FL suggests that the TL
      is the key element required for temperature activation in RNAP catalysis, and
      that the FL promotes TL transitions during nucleotide addition. We reveal
      characteristic differences in the catalytic parameters between thermophilic
      Thermus aquaticus and mesophilic Deinococcus radiodurans RNAPs and identify the
      FL as an adaptable element responsible for the observed differences. Mutations in
      the FL also significantly affect the rate of intrinsic RNA cleavage in a TL
      dependent manner. In contrast, much weaker effects of the FL and TL mutations on
      GreA-assisted RNA cleavage suggest that the FL-dependent TL transitions are not
      required for this reaction. Thus, functional interplay between the FL and TL is
      essential for various catalytic activities of RNAP and plays an adaptive role in
      catalysis by thermophilic and mesophilic enzymes. 

PMID- 24089148
TI  - A robust and simple-to-design multiplex DNA methylation assay based on MS-MLPA-CE
      SSCP.
AB  - Aberrant DNA methylation is a potential diagnostic marker for complex diseases,
      such as cancer. With the increase in the number of genes known to exhibit disease
      associated aberrant methylation, the need for accurate multiplex assays for
      quantifying DNA methylation has increased. Methylation-specific multiplex
      ligation-dependent probe amplification (MS-MLPA) is one method that has been
      highlighted in this context. However, two limitations make the custom design of
      MS-MLPA assays impractical: the need for long probes containing stuffer sequences
      and a reliance on only one restriction enzyme. Here, we developed a variation of
      MS-MLPA that employs a simpler probe-design process. To overcome the above
      mentioned limitations, we used stuffer-free MS-MLPA probes that are subsequently
      analyzed using high-resolution capillary electrophoresis-based single-strand
      conformational polymorphism (CE-SSCP) instead of conventional length-dependent
      CE. Moreover, multiple methylation-sensitive restriction enzymes (HhaI, HpaII,
      and AciI) were used simultaneously; thus, probes satisfying desired criteria were
      available for all targets. Using this assay concept, we analyzed 17 genes
      associated with hepatocellular carcinoma. Our results showed that the custom
      designed assay based on MS-MLPA-CE-SSCP provided robust multiplex quantification
      of DNA methylation levels. 

PMID- 24089149
TI  - Pathways to violent behavior during first-episode psychosis: a report from the UK
      National EDEN Study.
AB  - IMPORTANCE: Although many studies have explored the correlates of violence during
      first-episode psychosis (FEP), most have simply compared violent psychotic
      individuals with nonviolent psychotic individuals. Accumulating evidence suggests
      there may be subgroups within psychosis, differing in terms of developmental
      processes and proximal factors associated with violent behavior. OBJECTIVE: To
      determine whether there are subgroups of psychotic individuals characterized by
      different developmental trajectories to violent behavior. DESIGN, SETTING, AND
      PARTICIPANTS: The National EDEN (Evaluating the Development and Impact of Early
      Intervention Services in the West Midlands) Study longitudinal cohort assessed
      premorbid delinquency (premorbid adjustment adaptation subscale across childhood
      and adolescence), age at illness onset, duration of untreated psychosis, past
      drug use, positive symptoms, and violent behavior. Group trajectories of
      premorbid delinquency were estimated using latent class growth analysis, and
      associations with violent behavior were quantified. This study included 6 early
      intervention services in 5 geographical locations across England, with violent
      behavior information available for 670 first-episode psychosis cases. MAIN
      OUTCOMES AND MEASURES: Violent behavior at 6 or 12 months following early
      intervention services entry. RESULTS: Four groups of premorbid delinquency were
      identified: stable low, adolescent-onset high to moderate, stable moderate, and
      stable high. Logistic regression analysis, with stable low delinquency as the
      reference group, demonstrated that moderate (odds ratio, 1.97; 95% CI, 1.12-3.46)
      and high (odds ratio, 3.53; 95% CI, 1.85-6.73) premorbid delinquency trajectories
      increased the risk for violent behavior during FEP. After controlling for
      confounders, path analysis demonstrated that the increased risk for violence in
      the moderate delinquency group was indirect (ie, partially mediated by positive
      symptoms) (probit coefficient [beta] = 0.12; P = .002); while stable high
      delinquency directly increased the risk for violence (beta = 0.38; P = .05).
      CONCLUSIONS AND RELEVANCE: There appear to be diverse pathways to violent
      behavior during FEP. Stable high premorbid delinquency from childhood onwards
      appears to directly increase the risk for violent behavior, independent of
      psychosis-related risk factors. In addition to tackling illness-related risks,
      treatments should directly address antisocial traits as a potent risk for
      violence during FEP.

PMID- 24089150
TI  - Genetic diversity of the HLA-G coding region in Amerindian populations from the
      Brazilian Amazon: a possible role of natural selection.
AB  - HLA-G has an important role in the modulation of the maternal immune system
      during pregnancy, and evidence that balancing selection acts in the promoter and
      3'UTR regions has been previously reported. To determine whether selection acts
      on the HLA-G coding region in the Amazon Rainforest, exons 2, 3 and 4 were
      analyzed in a sample of 142 Amerindians from nine villages of five isolated
      tribes that inhabit the Central Amazon. Six previously described single
      nucleotide polymorphisms (SNPs) were identified and the Expectation-Maximization
      (EM) and PHASE algorithms were used to computationally reconstruct SNP haplotypes
      (HLA-G alleles). A new HLA-G allele, which originated in Amerindian populations
      by a crossing-over event between two widespread HLA-G alleles, was identified in
      18 individuals. Neutrality tests evidenced that natural selection has a complex
      part in the HLA-G coding region. Although balancing selection is the type of
      selection that shapes variability at a local level (Native American populations),
      we have also shown that purifying selection may occur on a worldwide scale.
      Moreover, the balancing selection does not seem to act on the coding region as
      strongly as it acts on the flanking regulatory regions, and such coding signature
      may actually reflect a hitchhiking effect. 

PMID- 24089151
TI  - Recommendations for term and late preterm infants at risk for perinatal bacterial
      infection.
AB  - Since publication of the initial guidelines for the prevention of group B
      streptococcal disease in 1996, the incidence of perinatal infection has decreased
      significantly. Intrapartum antibiotic prophylaxis together with appropriate
      management of neonates at increased risk for early-onset sepsis not only reduces
      morbidity and mortality, but also decreases the burden of unnecessary or
      prolonged antibiotic therapy. This article provides healthcare workers in
      Switzerland with evidence-based and best-practice derived guidelines for the
      assessment and management of term and late preterm infants (>34 weeks) at
      increased risk for perinatal bacterial infection. Management of neonates at
      increased risk for early-onset sepsis depends on clinical presentation and risk
      factors. Asymptomatic infants with risk factors for early-onset sepsis should be
      observed closely in an inpatient setting for the first 48 hours of life.
      Symptomatic neonates must be treated promptly with intravenous antibiotics. As
      clinical and laboratory signs of neonatal infection are nonspecific, it is
      mandatory to reevaluate the need for continued antibiotic therapy after 48 hours.

PMID- 24089153
TI  - Beyond survival in dialysis, we must change the paradigm.

PMID- 24089152
TI  - Distinguishing between genotoxic and non-genotoxic hepatocarcinogens by gene
      expression profiling and bioinformatic pathway analysis.
AB  - A rapid and sensitive method to determine the characteristics of carcinogens is
      needed. In this study, we used a microarray-based genomics approach, with a short
      term in vivo model, in combination with insights from statistical and mechanistic
      analyses to determine the characteristics of carcinogens. Carcinogens were
      evaluated based on the different mechanisms involved in the responses to
      genotoxic carcinogens and non-genotoxic carcinogens. Gene profiling was performed
      at two time points after treatment with six training and four test carcinogens.
      We mapped the DEG (differentially expressed gene)-related pathways to analyze
      cellular processes, and we discovered significant mechanisms that involve
      critical cellular components. Classification results were further supported by
      Comet and Micronucleus assays. Mechanistic studies based on gene expression
      profiling enhanced our understanding of the characteristics of different
      carcinogens. Moreover, the efficiency of this study was demonstrated by the short
      term nature of the animal experiments that were conducted. 

PMID- 24089154
TI  - A comparison of medium-term survival between peritoneal dialysis and
      haemodialysis in accordance with the initial vascular access.
AB  - INTRODUCTION: A study published in 2011 showed that patients in the Canary
      Islands, who were incident in peritoneal dialysis (PD) had better survival than
      those who were incident in hemodialysis (HD). Since initiating hemodialysis with
      central venous catheter is associated with worse prognosis, it would be possible
      that the initial vascular access influences the results of survival comparison
      between both groups. OBJECTIVE: To conduct a comparative medium-term survival
      study of patients incident in renal replacement therapy with different modalities
      in our community, classifying those incident in hemodialysis according to the
      initial vascular access: established arteriovenous vascular access or central
      venous catheter. MATERIAL AND METHOD: Retrospective longitudinal cohort study
      including all patients who were incident in renal replacement therapy between
      January 2005 and December 2010, with follow-up until December 2011, in three
      large hospitals of the Canary Islands. Patients were classified according to the
      initial modality: PD, HD with established vascular access (HD-FAV) or HD with
      central venous catheter (HD-Cat). Kaplan-Meier survival curves were estimated for
      each group and a Cox proportional hazards survival model was used to estimate
      relative mortality risk for DP as compared to HD-FAV and HD-Cat, adjusting for
      age and Charlson comorbidity index. An equivalent analysis was then conducted on
      subgroups defined by age or by the presence of diabetes. RESULTS: 1110 patients
      were included, with a median age of 63 years, 56% of them were diabetic. A Kaplan
      Meier analysis showed better survival for PD (66 months) as compared to HD-Cat
      (41 months), Log Rank p<.001, with no difference between DP and HD-FAV (67
      months). Cox regression RR of mortality for HD-Cat versus PD was 2.270 (1.573
      3.276); p<.001; no differences were found between HD-FAV and PD patients 0.993
      (0.646-1.525) n.s. Subgroup analysis showed equivalent results for diabetic and
      non-diabetic patients as well as for younger or older ones. CONCLUSIONS: better
      survival of PD patients as compared to HD ones, observed in the Canary Islands,
      seems to be based on incident HD patients with central venous catheter, while no
      differences were found between PD and HD with established vascular access. These
      results could suggest that patients in our community, for whom a vascular access
      cannot be achieved in predialysis, could have better survival if PD is offered as
      initial technique, at least until a vascular access is available.

PMID- 24089155
TI  - Progression of residual renal function with an increase in dialysis:
      haemodialysis versus peritoneal dialysis.
AB  - OBJECTIVE: The main objective of the study was to analyse the progression of
      residual renal function according to the dialysis technique (peritoneal dialysis
      or haemodialysis) and the frequency of treatment (two or three sessions of
      haemodialysis per week). As secondary objectives, we studied the progression of
      the serum concentration levels of beta2 microglobulin and the response of anaemia
      to erythropoietic agents. MATERIAL AND METHOD: 193 non-anuric patients were
      included and began renal replacement therapy with dialysis in our hospital
      between 1 January 2006 and 31 December 2011, with a follow-up period of over
      three months. 61 patients (32%) began treatment with two haemodialysis sessions
      per week, 49 patients (25%) with three haemodialysis sessions per week and 83
      patients (43%) with peritoneal dialysis. The glomerular filtration rate was
      measured as the mean of the renal clearances of urea and creatinine. RESULTS: The
      rate of decrease in glomerular filtration was the same in patients who began
      treatment with two haemodialysis sessions per week and with peritoneal dialysis
      (median 0.18 ml/min/month) and it was higher in patients who began treatment with
      three sessions of haemodialysis per week (median 0.33 ml/min/month, P<.05).
      Throughout progression, the glomerular filtration rate did not display
      differences between the group that began with two weekly sessions of
      haemodialysis and the group on peritoneal dialysis, and it was lower in the group
      that began treatment with three sessions of haemodialysis per week with
      statistical significance during the first 24 months of follow up. In the three
      patient groups, beta2-microglobulin concentration increased as the glomerular
      filtration rate decreased and it was higher in the group on three weekly
      haemodialysis sessions for the first 12 months of follow up. In all the controls
      carried out, there was a negative correlation between the beta-2 microglobulin
      concentration and the glomerular filtration rate (P<.001). The erythropoietin
      dose was negatively related to glomerular filtration. Patients who began with two
      sessions of haemodialysis per week required a lower dose of erythropoietin than
      patients that began renal replacement therapy with three weekly sessions. The
      erythropoietin dose in the peritoneal dialysis group was below that of the group
      of two weekly haemodialysis sessions despite maintaining a similar glomerular
      filtration rate. CONCLUSIONS: Patients who begin treatment with two sessions of
      haemodialysis per week experience the same rate of decrease in residual renal
      function as patients treated with peritoneal dialysis. The progression of the
      concentration of beta2-microglobulin is parallel to that of the glomerular
      filtration rate. Patients treated with two haemodialysis sessions require a lower
      dose of erythropoietin than those who receive three sessions per week, but a
      significantly higher dose than those treated with peritoneal dialysis, which
      suggests that the response of anaemia to erythropoietic agents is not only
      related to residual renal function, but also to other factors that are inherent
      to the dialysis technique.

PMID- 24089156
TI  - Carotid artery function in children with idiopathic nephrotic syndrome.
AB  - BACKGROUND: Nephrotic patients are prone to atherosclerosis in consequence of
      frequent exposures to hyperlipidemia, hypertension, and immunosuppressive drugs.
      OBJECTIVES: We studied the carotid parameters as early indicators of
      atherosclerosis in children with nephrotic syndrome. METHODS: Between 2008 and
      2011, 51 children with history of nephrotic syndrome enrolled in the study. The
      inclusion criteria were: idiopathic nephrotic syndrome with normal serum
      complement, at least one year after initiation of disease, glomerular filtration
      rate more than 20 mL/min/1.73 m2, age over two years old at the time of study.
      Seventy-five healthy sex-age-matched children considered as a control group.
      Carotid function parameters and left ventricular mass index were studied in
      nephrotic children. RESULTS: Steroid sensitive, resistant, and dependent
      nephrotic syndrome included one-third each. The mean carotid intima-media
      thickness (mm) in nephrotic children was 0.42 (+/-.14) while the mean cIMT in
      controls was 0.37 (+/-.08) (p-value <.05). After log transformation, General
      Linear Multivariate analysis revealed significant difference of carotid intima
      media thickness in nephrotic patients (p-value <.001). Subsequently, the factor
      that influenced on cIMT was duration of disease (P<.05). One-half of nephrotic
      children who had echocardiography, showed left ventricular hypertrophy. It was
      correlated with carotid stiffness and systolic hypertension (P<.05). CONCLUSIONS:
      Carotid intima-media thickness was thicker in nephrotic children. Carotid
      parameters were influenced by duration of disease and hypertension.

PMID- 24089157
TI  - High prevalence of secondary hyperparathyroidism in chronic kidney disease
      patients on dialysis in Argentina.
AB  - BACKGROUND: There are few data in Argentina on the prevalence and management of
      bone and mineral metabolism (BMM) in patients with chronic kidney disease (CKD).
      OBJECTIVES AND METHODS: A survey was carried out in dialysis units in 2010 to
      measure the prevalence of and types of treatments for BMM disorders in Argentina.
      The data obtained was then compared to the published results from other large
      population studies. We recorded characteristics of dialysis centres and
      participating patients, the frequency of measurements and individual results for
      BMM biochemical markers, as well as the type of management used to control
      hyperphosphataemia and secondary hyperparathyroidism. RESULTS: 1210 patients from
      25 dialysis centres in Argentina participated in the study (representing 4.7% of
      the country's prevalent dialysis population in 2010). The mean patient age was
      55.3+/-17.6 years, 60.8% were male, 3.3% were on peritoneal dialysis and 29.1%
      suffered diabetes. In all centres, phosphataemia and calcaemia were measured on a
      monthly basis, 60% of centres measured intact parathyroid hormone (iPTH) every 6
      months, 36% every 3 to 4 months, and 4% annually. As recommended by K/DOQI, 51.6%
      of patients had adequate levels of calcium (8.4-9.5 mg/dl), 51.6% had adequate
      phosphorus (3.5-5.5 mg/dl) and 21.1% displayed acceptable iPTH levels (150-300
      pg/ml). 24% had iPTH <150 pg/ml and 54.5% >300 pg/ml. iPTH >=600 pg/ml was
      present in 28.3%, and 13.3% had values >=1000 pg/ml. These figures differed from
      those published by the DOPPS II study, in which 51.1% of patients had iPTH <150
      pg/ml, and only 26.7% had iPTH >=300 pg/ml. Calcium-based phosphate binders were
      used in 83.6% of the patients, 5.6% used sevelamer and 4.0% used aluminium
      containing compounds. To achieve control of hyperparathyroidism, oral or
      intravenous calcitriol was predominantly used (50.5%) with a small percentage of
      patients receiving paricalcitol or doxercalciferol. CONCLUSIONS: The present
      study shows a high prevalence of secondary hyperparathyroidism, which differs
      from that published by other large population studies. There was a high
      proportion of patients with BMM markers outside the ranges suggested by K/DOQI.
      Mainly phosphate binders based on calcium and calcitriol continue to be used for
      the management of hyperphosphatemia and hyperparathyroidism respectively.

PMID- 24089158
TI  - Nutritional status and overhydration: can bioimpedance spectroscopy be useful in
      haemodialysis patients?
AB  - BACKGROUND: Protein-energy wasting (PEW), associated with inflammation and
      overhydration, is common in haemodialysis (HD) patients and is associated with
      high morbidity and mortality. OBJECTIVE: Assess the relationship between
      nutritional status, markers of inflammation and body composition through
      bioimpedance spectroscopy (BIS) in HD patients. METHODS: This observational,
      cross-sectional, single centre study, carried out in an HD centre in Forte da
      Casa (Portugal), involved 75 patients on an HD programme. In all participating
      patients, the following laboratory tests were conducted: haemoglobin, albumin, C
      reactive protein (CRP) and 25-hydroxyvitamin D3 [25(OH)D3]. The body mass index
      of all patients was calculated and a modified version of subjective global
      assessment (SGA) was produced for patients on dialysis. Intracellular water (ICW)
      and extracellular water (ECW) were measured by BIS (Body Composition Monitor(r),
      Fresenius Medical Care(r)) after the HD session. In statistical analysis,
      Spearman's correlation was used for the univariate analysis and linear regression
      for the multivariate analysis (SPSS 14.0). A P value of <.05 was considered
      statistically significant. RESULTS: PEW, inversely assessed through the ICW/body
      weight (BW) ratio, was positively related to age (P<.001), presence of diabetes
      (P=.004), BMI (P=.01) and CRP (P=.008) and negatively related to albumin (p=.006)
      and 25(OH)D3 (P=.007). Overhydration, assessed directly through the ECW/BW ratio,
      was positively related with CRP (P=.009) and SGA (P=.03), and negatively with
      25(OH)D3 (P=.006) and BMI (P=.01). In multivariate analysis, PEW was associated
      with older age (P<.001), the presence of diabetes (P=.003), lower 25(OH)D3
      (P=.008), higher CRP (P=.001) and lower albumin levels (P=.004). Overhydration
      was associated with higher CRP (P=.001) and lower levels of 25(OH)D3 (P=.003).
      CONCLUSIONS: Taking these results into account, the ICW/BW and ECW/BW ratios,
      assessed with BIS, have proven to be good markers of the nutritional and
      inflammatory status of HD patients. BIS may be a useful tool for regularly
      assessing the nutritional and hydration status in these patients and may allow
      nutritional advice to be improved and adjusted.

PMID- 24089159
TI  - Compliance with objectives based on different guidelines (KDIGO/S.E.N.) and
      analysis of the individual variability of mineral metabolism in haemodialysis
      patients in the medium term.
AB  - OBJECTIVE: To assess the level of compliance and variability of mineral
      metabolism parameters over time in a sample of haemodialysis patients for the
      different ranges proposed (KDIGO guidelines/S.E.N recommendations) in both groups
      and individuals continuously. MATERIAL AND METHOD: Every four months, we
      collected data on calcium, phosphorus, PTH and treatment in a sample of 44
      patients followed up continuously for 32 months. We established the percentages
      of patients who complied with the objectives set for each parameter in both
      ranges: optimal (KDIGO) and acceptable (S.E.N.) in each control and the
      percentage that individually complied with the objectives in at least 75% of the
      determinations. RESULTS: Compliance with the objective using the optimal range
      improved, although PTH did not exceed 50%. Using the acceptable range, the
      objective was achieved in the three parameters in over 70% and over 50% of
      patients achieved the three simultaneously while using the optimal range, 30% was
      never achieved. Individually, compliance with the optimal range was continuously
      achieved in 52.3% (calcium), 45.5% (phosphorus) and in only one patient in PTH,
      while when using the acceptable range, compliance was achieved in 84.1% (calcium)
      and 70.5% (phosphorus and PTH). CONCLUSIONS: The use of less stringent criteria
      than the KDIGO guidelines in calcium, phosphorus and PTH objectives allows
      patients to remain continuously within appropriate ranges with less intervention
      and less individual variability.

PMID- 24089160
TI  - Factors related with the progression of chronic kidney disease.
AB  - BACKGROUND: Our aims were to determine the rate of progression of chronic kidney
      disease (CKD) and to identify predictors, with particular emphasis on bone and
      mineral metabolism. METHODS: Retrospective and observational study including 300
      patients with advanced CKD (61.2% males, 33.1% diabetics; age 65.6+/-14 years).
      Mean follow-up time was 19.4+/-10.1 months. Baseline estimated glomerular
      filtration rate (eGFR) (MDRD-4) was 22.5+/-7.18 mL/min. To calculate the rate of
      decline in eGFR, we used the slope of the regression line between all
      determinations of eGFR and follow-up time. We calculated the mean values for
      proteinuria and serum phosphate, calcium, uric acid, and PTH, as well as 24-hour
      urinary excretion of urea nitrogen over time for each patient. Follow-up was at
      least 6 months and included at least 4 measurements of eGFR. RESULTS: The mean
      rate of decline eGFR (-1.64 mL/min/1.73 m2/year) was inversely correlated with
      serum phosphate levels (4.3+/-2.1 mg/dL, P<.001), PTH (256.3+/-193.7 ng/L,
      p<.001) and proteinuria (0.84+/-1.31 g/day, P=.004) and directly correlated with
      mean serum calcium (P<.001) and the presence of hypertension (P<.02). However,
      only serum phosphate, serum PTH, and proteinuria persisted as predictors in the
      multivariate analysis. Stable-GFR patients (positive slope) were older (P=.041)
      and had lower serum phosphate and PTH levels (P<.01 and P<.01 respectively) and
      lower proteinuria (P<.01). CONCLUSIONS: The rate of decrease in eGFR was
      correlated with serum phosphate and PTH levels and proteinuria. All of these
      factors can be modified with an adequate treatment.

PMID- 24089161
TI  - Multidisciplinary approach to hemodialysis graft dysfunction and thrombosis.
AB  - PURPOSE: Top analize the clinic results of the implantation of a
      multidisciplinary protocol to maintain permeability of the arteriovenous
      hemodialysis grafts (AVG). METHOD: Prospective recording of all interventions
      (radiological and surgical) on AVG dysfunction in the 1999-2007 period. The AVG
      stenosis were always treated by percutaneous angioplasty (PA) except stenosis
      recurrence in less than three months or persistence after PA. The AVG thromboses
      were always treated by surgical thrombectomy plus PTFE bridge if necessary.
      Complications, primary and secondary AVG patency were reviewed. RESULTS: Ninety
      six dysfunction AVG were collected for study. All of them were 6x40 mm standard
      wall PTFE (Gore-Tex(r)). Thirty six of them were humero-basilic antebraquial loop
      and sixty were humero-axillary upper arm curve configuration. During the study,
      52 PTFE bridges, 109 surgical thrombectomies, 131 PA, and 15 stents were needed
      to maintain FAVP permeability. Primay patency was 73.68%, 60.21% and 37.52% at
      one, two and three years respectively. Secondary patency was 89.49%, 84.07% and
      66.84% at one, two and three years respectively. We avoid a central venous
      catheter (CVC) in the 80% of intervention for thrombosis dysfunction. No surgical
      or radiological related deaths occurred. Median hospital admission related with
      AVG thrombosis was 0.03/patient/year. CONCLUSION: The application of a combined
      protocol for the treatment of AVG dysfunction and thrombosis, according to DOQI
      recomendations obtains good results in AVG patency in our experience.

PMID- 24089162
TI  - Attitudes of non-medical staff in hospitals in Spain, Mexico, Cuba and Costa Rica
      towards organ donation.
AB  - INTRODUCTION: Non-medical staff members in hospitals are highly credible at
      population level, and are a source of opinion even though they do not have
      sufficient medical training. OBJECTIVES: To analyse the attitudes of non-medical
      professionals of Spanish and Latin American hospitals towards organ donation and
      identify the factors that influence these attitudes. MATERIAL AND METHOD: Through
      the "Proyecto Colaborativo Internacional Donante" (International Collaborative
      Donor Project), a stratified random sample was selected from non-medical services
      of eleven hospitals: 3 Spanish (n=277), 5 Mexican (n=632), 2 Cuban (n=42) and 1
      Costa Rican (n=101). RESULTS: Of the 1052 professionals surveyed, 72% (n=754)
      were in favour of donating an organ after death. By country, 98% of Cubans, 80%
      of Mexicans, 66% of Costa Ricans and 52% of Spanish were in favour (P<.001). The
      most influential variables were: 1) country, with results being more positive in
      Mexico (odds ratio [OR]=2.197), 2) believing in the possibility that they will
      require a transplant (OR=2.202), 3) having discussed the issue with their family
      (OR=3.23), 4) the positive attitude of their partner towards donation (OR=3.322),
      5) not being concerned about possible mutilation of their body after donation
      (OR=3.378), 6) preferring options other than burial (OR=2.525), 7) accepting an
      autopsy (OR=2.958). CONCLUSIONS: The attitude of non-medical staff members of
      hospitals towards the donation of their own organs varies greatly depending on
      the country of the respondent. Psychosocial factors that influence these
      attitudes are similar to those described at the population level.

PMID- 24089163
TI  - Oral paricalcitol as antiproteinuric agent in chronic kidney disease.
AB  - BACKGROUND: Vitamin D has an important regulatory effect on the renin-angiotensin
      aldosterone system, playing a central role in the regulation of proteinuria. We
      therefore studied the antiproteinuric effect of paricalcitol. METHODS: 36
      patients with an estimated GFR of 30-90 mL/min/1.73 m2 and proteinuria >400 mg/d
      with a stable dose of ACE inhibitor or ARB for at least 3 months were recruited.
      Patients received oral paricalcitol 1 ug/day for 12 months. Primary endpoint was
      decrease in proteinuria from baseline. Secondary endpoints were changes in
      creatinine, eGFR, serum levels of calcium, phosphorus, iPTH, 25(OH)vitD, C
      Reactive Protein and blood presure. RESULTS: Mean proteinuria was 2806 mg/d and
      fell to 2199 mg/d at month 6 (p<.0001) and 1931.5 mg/d at month 12 (P<.0001).
      Patients with >3000 mg/d baseline proteinuria (n=12) saw smaller relative
      reductions in proteinuria (5956.9+/-2492.6 mg/d to 4220.4+/-2613 mg/d at 12
      months) than patients with <3000 mg/d baseline proteinuria (1371+/-627.5 mg/d to
      821.3+/-491.5mg/d at 12 months). There were no changes in BP, eGFR and CRP. We
      observed significant changes in serum levels of calcium, phosphorus, iPTH, 25(OH)
      vitamin D. CONCLUSION: Our study shows an important reduction in proteinuria with
      a low dose of oral paricalcitol in CKD, that is particularly robust with baseline
      proteinuria between 1-3 g/d.

PMID- 24089164
TI  - Vitamin D and proteinuria: a critical review of molecular bases and clinical
      experience.
AB  - Proteinuria is the main predictor of chronic kidney disease progression. Drugs
      that block the renin-angiotensin-aldosterone (RAA) system reduce proteinuria and
      slow down the progression of the disease. However, their effect is suboptimal,
      and residual proteinuria persists as an important predictor of renal impairment.
      Vitamin D has pleiotropic effects that could have an impact on these parameters.
      In this study, we critically review the molecular and experimental bases that
      suggest an antiproteinuric effect of vitamin D receptor (VDR) activation and the
      available evidence on its antiproteinuric effect in clinical practice. In animal
      models, we have observed the antiproteinuric effect of VDR activation, which
      could be due to direct protective action on the podocyte or other pleiotropic
      effects that slow down RAA system activation, inflammation and fibrosis. Clinical
      trials have generally been conducted in patients with a vitamin D deficiency or
      insufficiency and the main trial (VITAL) did not demonstrate that paricalcitol
      improved the study's primary endpoint (decrease in the urine albumin to
      creatinine ratio). In this sense, the information available is insufficient to
      advise the use of native vitamin D or VDR activators as renoprotective
      antiproteinuric drugs beyond the experimental level. Two Spanish clinical trials
      and one Italian trial attempted to determine the effect of paricalcitol and
      vitamin D on residual proteinuria in various clinical circumstances (PALIFE,
      NEFROVID and PROCEED).

PMID- 24089165
TI  - CD80, suPAR and nephrotic syndrome in a case of NPHS2 mutation.
AB  - BACKGROUND: Podocin mutations are characterized by progression to end stage renal
      disease and histologic findings of Focal Segmental Glomerulosclerosis (FSGS).
      CD80 is a podocytes protein that may play a role in proteinuria, particularly in
      Minimal Change Disease whereas the soluble urokinase receptor (suPAR) is
      characteristically elevated in the serum of FSGS patients. METHODS: In a patient
      with nephrotic syndrome and podocin mutation, urinary and serum CD80 as well as
      suPAR were measured using commercially available kits. Urinary CD80 molecular
      size was determined by western blot analysis. Glomerular staining for CD80 and
      podocin was performed. RESULTS: Patient displayed marked elevated CD80 and mildly
      increased suPAR urinary levels compared to controls. Serum CD80 level was within
      the range observed in normal controls. Serum suPAR level was elevated, albeit in
      the lower range reported for patients with primary FSGS. Immunofluorescence
      examination of kidney biopsy revealed glomerular CD80 expression. CONCLUSION: The
      combination of serum and urinary biomarkers can help differentiate various forms
      of FSGS. High urinary CD80 and elevated serum and urinary suPAR might represent a
      profile to differentiate this genetic form of FSGS from primary FSGS.

PMID- 24089166
TI  - Can acute renal failure be complicated by renal compartment syndrome? A new view
      of an old idea.

PMID- 24089167
TI  - Bardet-Biedl syndrome, the ciliopathy model and the importance of renal
      involvement.

PMID- 24089168
TI  - Ischaemic colitis in haemodialysis.

PMID- 24089169
TI  - Treatment-resistant Churg-Strauss syndrome: progression after five years using
      rituximab.

PMID- 24089170
TI  - Transovarial venous access in a patient with exhausted vascular access for
      haemodialysis.

PMID- 24089171
TI  - The pros and cons of plasmapheresis therapy carried out on time.

PMID- 24089172
TI  - Infection due to Pneumocystis jirovecii in haemodialysis.

PMID- 24089173
TI  - Percutaneous treatment of an arteriovenous fistula and a pseudoaneurysm after a
      transplanted kidney biopsy.

PMID- 24089174
TI  - Membranous glomerulonephritis in a patient with Hodgkin's lymphoma in remission.

PMID- 24089175
TI  - Novel NPHS1 gene mutation in an Iranian patient with congenital nephrotic
      syndrome of the Finnish type.

PMID- 24089176
TI  - Stauffer syndrome and prostate carcinoma, two cases in chronic haemodialysis
      patients.

PMID- 24089178
TI  - Ethical considerations in healthcare design and construction.

PMID- 24089177
TI  - Congenital cutaneous histiocytosis in a piglet.
AB  - A 2-week-old crossbred male piglet with numerous congenital, variably sized
      macules, plaques, and papules distributed all over the body was submitted for
      necropsy. Significant gross and histological lesions were restricted to the skin.
      On light microscopic examination, these cutaneous lesions corresponded to dermal
      and/or subcutaneous masses composed of spindle-shaped to round cells that
      multifocally contained hemosiderin; epidermotropism was not observed.
      Immunohistochemically, the neoplastic cells were strongly positive for CD204;
      moderately positive for CD163, lysozyme, and vimentin; and negative for Mac 387,
      alpha-1-antitrypsin, S-100 protein and E-cadherin; frozen tissues were not
      available for CD1a and CD11c. Transmission electron microscopic examination of
      sections from formalin-fixed tissues did not reveal Birbeck's granules. The
      clinical, morphological, and immunohistochemical results were consistent with a
      congenital cutaneous histiocytosis of non-Langerhans cell origin. The condition
      most resembled juvenile xanthogranuloma in humans, a generally skin-limited non
      Langerhans histiocytic disorder that can be congenital. Cutaneous and/or systemic
      histiocytic disorders are well characterized in dogs and have been described in
      cats, and a case with some similarities to ours has been reported in a neonatal
      piglet, but this is to our knowledge the first immunohistochemically supported
      report of histiocytosis in the pig and congenital histiocytosis in animals. 

PMID- 24089179
TI  - Color Perception in Pediatric Patient Room Design: American versus Korean
      Pediatric Patients.
AB  - OBJECTIVE: This study simultaneously addresses the issues of the scarcity of
      information about pediatric patient color preferences, conflicting findings about
      the impact of culture on color preferences, and limitations of previous research
      instruments. Effects of culture and gender on color preferences were investigated
      using American and Korean pediatric patients. BACKGROUND: Much of the existing
      research in environmental design has focused on environments for healthy children
      and adults, but those findings cannot be confidently applied to environments for
      pediatric patients. In previous studies, the impact of culture on color
      preferences has been suggested, though the effects appear to vary. Moreover, the
      results of previous studies were typically based on perceptions of small color
      chips, which are different from seeing a color on wall surfaces. Previous studies
      also failed to control for confounding variables such as color attributes and
      light sources. METHODS: Instead of using color chips, this study used physical
      model simulation to investigate environmental color preferences in real contexts.
      RESULTS: Cultural difference was found in white. Other than white, no significant
      cultural difference was found. Gender differences were found across both of the
      groups. CONCLUSIONS: Korean pediatric patients showed significantly higher
      preference scores for white than Americans did. Other than white, both groups
      reported blue and green as their most preferred colors; white was the least
      preferred. Both groups reported similar gender effects. Overall, male patients
      reported significantly lower preference scores for red and purple than female
      patients did. These results can help healthcare providers and professionals
      better understand appropriate colors for pediatric populations. KEYWORDS:
      Evidence-based design, healing environment, patients, pediatric, satisfaction.

PMID- 24089180
TI  - Design for the post-antibiotic era: experiences from a new building for
      infectious diseases in malmo, sweden.
AB  - OBJECTIVE: To describe the experience of planning and designing a new facility
      for infectious diseases in Sweden and to discuss underlying theories relating to
      infection prevention and evidence-based design. BACKGROUND: Departments of
      Infectious Diseases are common in healthcare facililties in Sweden. In 2005, a
      decision was made to build a new facility. The program required spacious single
      rooms, with a high ventilation standard, and anterooms. METHODS: In this article
      we present an analysis of the future of infectious diseases. Underlying theories
      are discussed. We also describe how a program was outlined using literature
      studies, including evidence-based healthcare design, focus groups of staff, and
      study visits. RESULTS: Active involvement of users and infection control
      specialists was important in the building process. A full-scale patient room mock
      up was built with ventilation, electrical, and other systems. The mock-up was
      cost effective because it avoided costly mistakes during the building process.
      The mock-up also was a place where staff could assess and begin adapting to their
      future work environment. Separate ventilation and separate entrances to patient
      rooms from the building exterior allowed placement of isolation units in the main
      hospital area. CONCLUSIONS: Antimicrobial resistance, emerging diseases,
      healthcare associated infections, and outbreaks highlight the need for infection
      control measures in all hospital design. Infection control should be integrated
      in all hospital planning and be part of contracts. In this study we describe a
      specialized unit where a high degree of standardization and flexibility has made
      it possible to have a unique standard of preparedness for the post-antibiotic
      era. KEYWORDS: Design process, evidence-based design, infection control,
      planning, safety.

PMID- 24089181
TI  - Environmental affordances: designing for family presence and involvement in
      patient care.
AB  - OBJECTIVE: This comparative study in two ICUs examines the impact of the patient
      centered unit design on family involvement, operationalized as percentages of
      family presence and family-patient/family-staff interaction in patient rooms.
      BACKGROUND: As hospitals have become more patient-centered, there has been a
      trend toward including a family area inside the patient area to promote family
      presence, support, and involvement in patient care. There is growing evidence
      that family members play an important role in supporting patient care, and that
      the physical environment affects family involvement. However, few empirical
      studies have attempted to show the effectiveness of the patient-centered design
      on family members' presence and their behavior. METHODS: This study compared the
      degree of family presence and family-patient and family-staff interactions in two
      intensive care units (ICUs) with different physical environmental conditions, but
      housing patients of similar acuity and disease type. RESULTS: The analysis
      identified a significant difference in family presence in patient rooms (t = 
      2.176; df = 79.0; p = 0.03) between the traditional and the patient-centered
      units. Patients in the family-centered care unit (M = 37.77; SD = 34.02) spent
      significantly more time with their family members in patient rooms than did
      patients in the traditional unit (M = 23.89; SD = 21.90). Patient-related
      variables other than unit design had no significant impact on family presence and
      interactions. CONCLUSIONS: Findings demonstrated that the patient-centered unit
      (5K) was associated with increased family presence in the patient rooms and
      increased family interaction with patients, when compared with the traditionally
      designed unit. KEYWORDS: Critical care/intensive care, evidence-based design,
      patient-centered care, quality care, social support.

PMID- 24089182
TI  - Barriers to Garden Visitation in Children's Hospitals.
AB  - OBJECTIVE: This study aimed to identify barriers to use of outdoor spaces in
      Texas pediatric healthcare facilities. BACKGROUND: Available research on hospital
      healing gardens and outdoor spaces has indicated that despite several health
      benefits of garden visitation for staff, patients, and family members, these
      amenities are not being used to their fullest capacity. Previous researchers have
      recommended design features such as comfortable seats and adequate shade to
      increase garden visitation in healthcare setting. However no quantitative data
      have demonstrated significance of correlation between presence of these design
      features and garden use. The present study served to statistically support design
      guidelines suggested by previous researchers and introduce new guidelines.
      METHODS: Site visits and surveys were conducted in five green outdoor spaces in
      three pediatric hospitals in east Texas. Hospital visitors, family members, and
      staff responded to questions concerning barriers to garden visitation, their
      visitation habits, and satisfaction with the garden features. The study was
      reviewed and approved by Institutional Review Boards of the relevant hospitals
      and academic institutions. RESULTS: A negative significant correlation was found
      between staff garden use and dissatisfaction with quality of seats and poor
      shade. While quality of seats didn't impact visitor and family member garden
      visitation, a significant negative correlation was found between poor shade and
      their garden use. CONCLUSIONS: The study served to statistically support previous
      design suggestions for hospital gardens, and introduced new design guidelines.
      Design recommendations include functionality, visibility, accessibility,
      exclusivity, and availability of shade and seats. KEYWORDS: Design process,
      evidence-based design, healing environments, hospital.

PMID- 24089183
TI  - Research informed design supports evidence-based ICU medicine.

PMID- 24089184
TI  - The question of knowledge in evidence-based design for healthcare facilities:
      limitations and suggestions.
AB  - OBJECTIVE: To help designers and researchers and other proponents of evidence
      based design (EBD) overcome limitations concerning knowledge categorization and
      acquisition of evidence-based design (EBD). BACKGROUND: The evidence-based design
      (EBD) approach for healthcare facilities has been widely embraced by both
      designers and researchers in recent years; however, there are some limitations
      concerning knowledge categorization and acquisition of EBD. These limitations
      include an overemphasis on empirical knowledge gained by experimental research, a
      narrow focus that excludes design knowledge generated outside healthcare and
      allied fields, and a lack of interest in empirical knowledge gained by
      qualitative studies. In order to overcome these limitations, the proponents of
      EBD must acknowledge that design knowledge relevant to healthcare design can be
      found in disciplines unrelated to healthcare; that design knowledge does not
      always need empirical validation; and that design knowledge of the semantic kind
      can be more easily accessed and understood through qualitative studies.
      CONCLUSIONS: To reassess the foundations of knowledge of EBD with moderated
      skepticism is necessary because there are philosophical and analytical problems
      yet to be overcome in delivering on the promises of EBD. To question and reassess
      the foundations of knowledge base of EBD is not necessarily to deny its value,
      but rather to stimulate a judicious and balanced appraisal of its limitations so
      that, in future, we are able to take necessary steps to overcome these
      limitations. KEYWORDS: Design process, evidence-based design, methodology,
      theory, interdisciplinary.

PMID- 24089185
TI  - Stressed spaces: mental health and architecture.
AB  - OBJECTIVE: To present a comprehensive review of the research literature on the
      effects of the architectural designs of mental health facilities on the users.
      BACKGROUND: Using a team of cross-disciplinary researchers, this review builds
      upon previous reviews on general and geriatric healthcare design in order to
      focus on research undertaken for mental health care facility design. METHODS:
      Sources were gathered in 2010 and 2011. In 2010 a broad search was undertaken
      across health and architecture; in 2011, using keywords and 13 databases,
      researchers conducted a systematic search of peer reviewed literature addressing
      mental health care and architectural design published between 2005 to 2012, as
      well as a systematic search for academic theses for the period 2000 to 2012.
      Recurrent themes and subthemes were identified and numerical data that emerged
      from quantitative studies was tabulated. RESULTS: Key themes that emerged were
      nursing stations, light, therapeutic milieu, security, privacy, designing for the
      adolescent, forensic facilities, interior detail, patients' rooms, art, dementia,
      model of care, gardens, post-occupancy evaluation, and user engagement in design
      process. Of the 165 articles (including conference proceedings, books, and
      theses), 25 contained numerical data from empirical studies and 7 were review
      articles. CONCLUSIONS: Based on the review results, especially the growing
      evidence of the benefits of therapeutic design on patient and staff well-being
      and client length of stay, additional research questions are suggested concerning
      optimal design considerations, designs to be avoided, and the involvement of
      major stakeholders in the design process. KEYWORDS: Evidence-based design,
      hospital, interdisciplinary, literature review, post-occupancy.

PMID- 24089186
TI  - Understanding evidence-based research methods: confirmatory and exploratory
      analysis.

PMID- 24089187
TI  - Hospital architecture.

PMID- 24089188
TI  - Empirical validation of viral quasispecies assembly algorithms: state-of-the-art
      and challenges.
AB  - Next generation sequencing (NGS) is superseding Sanger technology for analysing
      intra-host viral populations, in terms of genome length and resolution. We
      introduce two new empirical validation data sets and test the available viral
      population assembly software. Two intra-host viral population 'quasispecies'
      samples (type-1 human immunodeficiency and hepatitis C virus) were Sanger
      sequenced, and plasmid clone mixtures at controlled proportions were shotgun
      sequenced using Roche's 454 sequencing platform. The performance of different
      assemblers was compared in terms of phylogenetic clustering and recombination
      with the Sanger clones. Phylogenetic clustering showed that all assemblers
      captured a proportion of the most divergent lineages, but none were able to
      provide a high precision/recall tradeoff. Estimated variant frequencies mildly
      correlated with the original. Given the limitations of currently available
      algorithms identified by our empirical validation, the development and
      exploitation of additional data sets is needed, in order to establish an
      efficient framework for viral population reconstruction using NGS. 

PMID- 24089190
TI  - Cutting Edge: CD1a tetramers and dextramers identify human lipopeptide-specific T
      cells ex vivo.
AB  - Human CD1a mediates foreign Ag recognition by a T cell clone, but the nature of
      possible TCR interactions with CD1a/lipid are unknown. After incubating CD1a with
      a mycobacterial lipopeptide Ag, dideoxymycobactin (DDM), we identified and
      measured binding to a recombinant TCR (TRAV3/ TRBV3-1, KD of ~100 MUM). Detection
      of ternary CD1a/lipid/TCR interactions enabled development of CD1a tetramers and
      CD1a multimers with carbohydrate backbones (dextramers), which specifically
      stained T cells using a mechanism that was dependent on the precise
      stereochemistry of the peptide backbone and was blocked with a soluble TCR.
      Furthermore, sorting of human T cells from unrelated tuberculosis patients for
      bright DDM-dextramer staining allowed recovery of T cells that were activated by
      CD1a and DDM. These studies demonstrate that the mechanism of T cell activation
      by lipopeptides occurs via ternary interactions of CD1a/Ag/TCR. Furthermore,
      these studies demonstrate the existence of lipopeptide-specific T cells in humans
      ex vivo. 

PMID- 24089191
TI  - Influenza A exacerbates Staphylococcus aureus pneumonia by attenuating IL-1beta
      production in mice.
AB  - Pneumonia is a leading cause of death worldwide. Staphylococcal aureus can be a
      cause of severe pneumonia alone or a common pathogen in secondary pneumonia
      following influenza. Recently, we reported that preceding influenza attenuated
      the Type 17 pathway, increasing the lung's susceptibility to secondary infection.
      IL-1beta is known to regulate host defense, including playing a role in Th17
      polarization. We examined whether IL-1beta signaling is required for S. aureus
      host defense and whether influenza infection impacted S. aureus-induced IL-1beta
      production and subsequent Type 17 pathway activation. Mice were challenged with
      S. aureus (USA 300), with or without preceding Influenza A/PR/8/34 H1N1
      infection. IL-1R1(-/-) mice had significantly higher S. aureus burden, increased
      mortality, and decreased Type 17 pathway activation following S. aureus
      challenge. Coinfected mice had significantly decreased IL-1beta production versus
      S. aureus infection alone at early time points following bacterial challenge.
      Preceding influenza did not attenuate S. aureus-induced inflammasome activation,
      but there was early suppression of NF-kappaB activation, suggesting an inhibition
      of NF-kappaB-dependent transcription of pro-IL-1beta. Furthermore, overexpression
      of IL-1beta in influenza and S. aureus-coinfected mice rescued the induction of
      IL-17 and IL-22 by S. aureus and improved bacterial clearance. Finally, exogenous
      IL-1beta did not significantly rescue S. aureus host defense during coinfection
      in IL-17RA(-/-) mice or in mice in which IL-17 and IL-22 activity were blocked.
      These data reveal a novel mechanism by which Influenza A inhibits S. aureus
      induced IL-1beta production, resulting in attenuation of Type 17 immunity and
      increased susceptibility to bacterial infection. 

PMID- 24089189
TI  - Coadministration of polyinosinic:polycytidylic acid and immunostimulatory
      complexes modifies antigen processing in dendritic cell subsets and enhances HIV
      gag-specific T cell immunity.
AB  - Currently approved adjuvants induce protective Ab responses but are more limited
      for generating cellular immunity. In this study, we assessed the effect of
      combining two adjuvants with distinct mechanisms of action on their ability to
      prime T cells: the TLR3 ligand, polyinosinic:polycytidylic acid (poly I:C), and
      immunostimulatory complexes (ISCOMs). Each adjuvant was administered alone or
      together with HIV Gag protein (Gag), and the magnitude, quality, and phenotype of
      Gag-specific T cell responses were assessed. For CD8 T cells, all adjuvants
      induced a comparable response magnitude, but combining poly I:C with ISCOMs
      induced a high frequency of CD127(+), IL-2-producing cells with decreased
      expression of Tbet compared with either adjuvant alone. For CD4 T cells,
      combining poly I:C and ISCOMs increased the frequency of multifunctional cells,
      producing IFN-gamma, IL-2, and TNF, and the total magnitude of the response
      compared with either adjuvant alone. CD8 or CD4 T cell responses induced by both
      adjuvants mediated protection against Gag-expressing Listeria monocytogenes or
      vaccinia viral infections. Poly I:C and ISCOMs can alter Ag uptake and/or
      processing, and we therefore used fluorescently labeled HIV Gag and DQ-OVA to
      assess these mechanisms, respectively, in multiple dendritic cell subsets. Poly
      I:C promoted uptake and retention of Ag, whereas ISCOMs enhanced Ag degradation.
      Combining poly I:C and ISCOMs caused substantial death of dendritic cells but
      persistence of degraded Ag. These data illustrate how combining adjuvants, such
      as poly I:C and ISCOMs, that modulate Ag processing and have potent innate
      activity, can enhance the magnitude, quality, and phenotype of T cell immunity. 

PMID- 24089192
TI  - Mitochondrial reactive oxygen species induces NLRP3-dependent lysosomal damage
      and inflammasome activation.
AB  - The nucleotide-binding oligomerization domain-like receptor family, pyrin domain
      containing 3 (NLRP3) inflammasome drives many inflammatory processes and mediates
      IL-1 family cytokine release. Inflammasome activators typically damage cells and
      may release lysosomal and mitochondrial products into the cytosol. Macrophages
      triggered by the NLRP3 inflammasome activator nigericin show reduced
      mitochondrial function and decreased cellular ATP. Release of mitochondrial
      reactive oxygen species (ROS) leads to subsequent lysosomal membrane
      permeabilization (LMP). NLRP3-deficient macrophages show comparable reduced
      mitochondrial function and ATP loss, but maintain lysosomal acidity,
      demonstrating that LMP is NLRP3 dependent. A subset of wild-type macrophages
      undergo subsequent mitochondrial membrane permeabilization and die. Both LMP and
      mitochondrial membrane permeabilization are inhibited by potassium, scavenging
      mitochondrial ROS, or NLRP3 deficiency, but are unaffected by cathepsin B or
      caspase-1 inhibitors. In contrast, IL-1beta secretion is ablated by potassium,
      scavenging mitochondrial ROS, and both cathepsin B and caspase-1 inhibition.
      These results demonstrate interplay between lysosomes and mitochondria that
      sustain NLRP3 activation and distinguish cell death from IL-1beta release. 

PMID- 24089193
TI  - Systemic disease during Streptococcus pneumoniae acute lung infection requires 12
      lipoxygenase-dependent inflammation.
AB  - Acute pulmonary infection by Streptococcus pneumoniae is characterized by high
      bacterial numbers in the lung, a robust alveolar influx of polymorphonuclear
      cells (PMNs), and a risk of systemic spread of the bacterium. We investigated
      host mediators of S. pneumoniae-induced PMN migration and the role of
      inflammation in septicemia following pneumococcal lung infection. Hepoxilin A3
      (HXA3) is a PMN chemoattractant and a metabolite of the 12-lipoxygenase (12-LOX)
      pathway. We observed that S. pneumoniae infection induced the production of 12
      LOX in cultured pulmonary epithelium and in the lungs of infected mice.
      Inhibition of the 12-LOX pathway prevented pathogen-induced PMN transepithelial
      migration in vitro and dramatically reduced lung inflammation upon high-dose
      pulmonary challenge with S. pneumoniae in vivo, thus implicating HXA3 in
      pneumococcus-induced pulmonary inflammation. PMN basolateral-to-apical
      transmigration in vitro significantly increased apical-to-basolateral
      transepithelial migration of bacteria. Mice suppressed in the expression of 12
      LOX exhibited little or no bacteremia and survived an otherwise lethal pulmonary
      challenge. Our data suggest that pneumococcal pulmonary inflammation is required
      for high-level bacteremia and systemic infection, partly by disrupting lung
      epithelium through 12-LOX-dependent HXA3 production and subsequent PMN
      transepithelial migration. 

PMID- 24089194
TI  - Phenotypic polarization of activated astrocytes: the critical role of lipocalin-2
      in the classical inflammatory activation of astrocytes.
AB  - Astrocytes provide structural and functional support for neurons, as well as
      display neurotoxic or neuroprotective phenotypes depending upon the presence of
      an immune or inflammatory microenvironment. This study was undertaken to
      characterize multiple phenotypes of activated astrocytes and to investigate the
      regulatory mechanisms involved. We report that activated astrocytes in culture
      exhibit two functional phenotypes with respect to pro- or anti-inflammatory gene
      expression, glial fibrillary acidic protein expression, and neurotoxic or
      neuroprotective activities. The two distinct functional phenotypes of astrocytes
      were also demonstrated in a mouse neuroinflammation model, which showed pro- or
      anti-inflammatory gene expression in astrocytes following challenge with
      classical or alternative activation stimuli; similar results were obtained in the
      absence of microglia. Subsequent studies involving recombinant lipocalin-2 (LCN2)
      protein treatment or Lcn2-deficient mice indicated that the pro- or anti
      inflammatory functionally polarized phenotypes of astrocytes and their
      intracellular signaling pathway were critically regulated by LCN2 under in vitro
      and in vivo conditions. Astrocyte-derived LCN2 promoted classical proinflammatory
      activation of astrocytes but inhibited IL-4-STAT6 signaling, a canonical pathway
      involved in alternative anti-inflammatory activation. Our results suggest that
      the secreted protein LCN2 is an autocrine modulator of the functional
      polarization of astrocytes in the presence of immune or inflammatory stimuli and
      that LCN2 could be targeted therapeutically to dampen proinflammatory astrocytic
      activation and related pathologies in the CNS. 

PMID- 24089196
TI  - The last century of symptom-oriented research in emergency presentations--have we
      made any progress?
AB  - This review is dedicated to the last century of symptom-oriented research, taking
      three symptom complexes as typical examples of medical progress, and focusing on
      emergency presentations. Landmark publications in each area are discussed, with
      an attempt to focus on the methods used to achieve major breakthroughs. In
      abdominal pain, progress was achieved over a century ago by correlating symptoms
      and surgical pathology. Most diagnoses were made by using the clinical tools
      elaborated with careful observation and clinical examination. Together with the
      later reported outcomes, surgeons had an early and powerful tool for symptom
      oriented research. In dyspnoea, progress was achieved much later, as a universal
      definition had to be elaborated over decades by consolidating clinical research,
      predominantly symptom-pathology correlation, and experimental research, such as
      function testing and experiments with animals and humans. In nonspecific
      presentations in emergency situations, progress has been achieved only recently,
      most probably owing to the fact that elderly patients are presenting in steeply
      increasing numbers, and the hallmark of disease presentation in the elderly seems
      to be less specific symptoms and complaints. This may be caused by altered
      physiology, polymorbidity, polypharmacy and the multiple difficulties encountered
      when taking histories in the elderly. Taken together, symptom-oriented research
      has been an important contributor to medical progress in the last century. Though
      it may be challenged by image- and laboratory-oriented research, it will remain
      part of patient-centred research because the epidemiology of symptoms, their
      clinical outcomes and their diagnostic importance according to severity will be
      the basis for the diagnostic process. 

PMID- 24089195
TI  - Thermal activation of catalytic microjets in blood samples using microfluidic
      chips.
AB  - We demonstrate that catalytic microjet engines can out-swim high complex media
      composed of red blood cells and serum. Despite the challenge presented by the
      high viscosity of the solution at room temperature, the catalytic microjets can
      be activated at physiological temperature and, consequently, self-propel in
      diluted solutions of blood samples. We prove that these microjets self-propel in
      10* diluted blood samples using microfluidic chips. 

PMID- 24089197
TI  - Chemical-physical analysis of a tartrate model compound for TACE inhibition.
AB  - We have synthesized and done an extensive chemical-physical analysis of the
      behavior of a new compound, named MBET306, a synthetic precursor of the recently
      discovered tartrate-based inhibitors of the protein Tumor Necrosis factor-alpha
      Converting Enzyme (TACE). Experimental and theoretical data have shown that in
      water solution MBET306 is overwhelmingly found as a monoanion at physiological
      pH, in a conformation that differs substantially from that detected in the known
      co-crystal structures of MBET306 derivatives bound to TACE. The body of collected
      experimental and theoretical data indicates that the monoanionic species binds
      Zn(ii) inducing a strong stabilization of the crystal-like arrangement of the
      central tartrate zinc-binding group, lending support for a two step TACE docking
      mechanism via a zinc-bound intermediate. The thorough chemical-physical
      characterization of the conformational behavior of free and zinc-bound MBET306 in
      water bulk solution opens new avenues for the rational drug design of tartrate
      based highly specific TACE inhibitors. 

PMID- 24089198
TI  - Retinoblastoma protein (RB1) controls fate determination in stem cells and
      progenitors of the mouse male germline.
AB  - Continual spermatogenesis is the cornerstone of male fertility and relies on the
      actions of an undifferentiated spermatogonial population comprised of stem cells
      and progenitors. A foundational spermatogonial stem cell (SSC) pool is
      established during postnatal development that serves as a self-renewing reservoir
      from which progenitor spermatogonia arise that transiently amplify in number
      before committing to terminal differentiation. At present, the underlying
      molecular mechanisms governing these actions are undefined. Using conditional
      mutant mouse models, we investigated whether function of the undifferentiated
      spermatogonial population during postnatal life is influenced by the tumor
      suppressor protein RB1. Spermatogenesis initiates in mice with conditional
      inactivation of Rb1 in prospermatogonial precursors, but the germline is
      progressively lost upon aging due to impaired renewal of the undifferentiated
      spermatogonial population. In contrast, continual spermatogenesis is sustained
      following Rb1 inactivation in progenitor spermatogonia, but some cells transform
      into a carcinoma in situ-like state. Furthermore, knockdown of Rb1 abundance
      within primary cultures of wild-type undifferentiated spermatogonia impairs
      maintenance of the SSC pool, and some cells are invasive of the basement membrane
      after transplant into recipient testes, indicating acquisition of tumorigenic
      properties. Collectively, these findings indicate that RB1 plays an essential
      role in establishment of a self-renewing SSC pool and commitment to the
      spermatogenic lineage within progenitor spermatogonia. 

PMID- 24089199
TI  - Aberrant epigenetic modification in murine brain tissues of offspring from
      preimplantation genetic diagnosis blastomere biopsies.
AB  - Preimplantation genetic diagnosis (PGD) has been prevalent in the field of
      assisted reproductive technology, yet the long-term risks of PGD to offspring
      remain unknown. In the present study, the early development of PGD embryos,
      postimplantation characteristics, and birth rate following PGD were determined.
      Moreover, the behavior of the offspring conceived from the biopsied embryos was
      evaluated with the Morris water maze and pole climbing tests. Finally, the
      epigenetic modification of the global genome and methylation patterns for the
      H19, Igf2, and Snrpn imprinted genes were identified. The results indicated a
      significant delay in the blastocoel formation of PGD embryos and a decrease in
      the implantation ability of these embryos, which was related to the decreased
      number of cells in the PGD blastocysts. The PGD mice spent more time on both the
      nontrained quadrant of the water maze and climbing down the pole. Furthermore,
      the 5-hydroxymethylcytosine content in the brain tissues of PGD mice was
      significantly increased, but no difference was found in 5-methylcytosine content.
      The differentially methylated regions of H19/Igf2 exhibited decreased methylation
      patterns, but that of Snrpn was normal, compared to the control group.
      Quantitative RT-PCR indicated that Igf2 mRNA expression was significantly
      decreased but that H19 and Snrpn mRNAs were expressed normally. In conclusion,
      blastomere biopsies in PGD procedures carry potential risks to embryo development
      and the behavior of resulting offspring; these risks may arise from aberrant
      epigenetic modification and methylation patterns in brain tissues. Further
      studies are needed to better understand the risks associated with PGD. 

PMID- 24089200
TI  - Selective ablation of Ppp1cc gene in testicular germ cells causes oligo
      teratozoospermia and infertility in mice.
AB  - The four isoforms of serine/threonine phosphoprotein phosphatase 1 (PP1), derived
      from three genes, are among the most conserved proteins known. The Ppp1cc gene
      encodes two alternatively spliced variants, PP1 gamma1 (PPP1CC1) and PP1 gamma2
      (PPP1CC2). Global deletion of the Ppp1cc gene, which causes loss of both
      isoforms, results in male infertility due to impaired spermatogenesis. This
      phenotype was assumed to be due to the loss of PPP1CC2, which is abundant in
      testis. While PPP1CC2 is predominant, other PP1 isoforms are also expressed in
      testis. Given the significant homology between the four PP1 isoforms, the lack of
      compensation by the other PP1 isoforms for loss of one, only in testis, is
      surprising. Here we document, for the first time, expression patterns of the PP1
      isoforms in postnatal developing and adult mouse testis. The timing and sites of
      testis expression of PPP1CC1 and PPP1CC2 in testis are nonoverlapping. PPP1CC2 is
      the only one of the four PP1 isoforms not detected in sertoli cells and
      spermatogonia. Conversely, PPP1CC2 may be the only PP1 isoform expressed in
      postmeiotic germ cells. Deletion of the Ppp1cc gene in germ cells at the
      differentiated spermatogonia stage of development and beyond in Stra8 promoter
      driven Cre transgenic mice results in oligo-terato-asthenozoospermia and male
      infertility, thus phenocopying global Ppp1cc null (-/-) mice. Taken together,
      these results confirm that spermatogenic defects observed in the global Ppp1cc
      knockout mice and in mice expressing low levels of PPP1CC2 in testis are due to
      compromised functions of PPP1CC2 in meiotic and postmeiotic germ cells. 

PMID- 24089201
TI  - Investigating the role of tbx4 in the female germline in mice.
AB  - Normal development of germ cells is essential for fertility and mammalian
      reproduction. Although abnormal development of oocytes or follicles may lead to
      primary ovarian insufficiency (POI), a disorder that causes infertility in 1% of
      women less than 40 yr of age, the genes and signaling pathways activated in POI
      are not as yet fully elucidated. Tbx4, a member of the T-box family of
      transcription factors, is expressed in embryonic germ cells and postnatal oocytes
      at all stages of folliculogenesis. To investigate the requirement for Tbx4 in the
      germline, we analyzed germ cell development in the absence of Tbx4. We show that
      primordial germ cells (PGCs) are reduced in Tbx4 homozygous null (Tbx4(-/-))
      embryos at Embryonic Day (E) 10.0. Tbx4(-/-) embryos die by E10.5; to study later
      time points in vitro, a tamoxifen-inducible estrogen receptor Cre recombinase was
      used to delete Tbx4 conditional mutant alleles. In addition, Gdf9cre and Zp3cre,
      two oocyte-specific Cre recombinases, were used to delete Tbx4 from postnatal
      primordial and primary follicles, respectively. We show that in vitro
      differentiation of the gonad into morphologically distinct testes and ovaries
      occurs normally starting at E11.5 when Tbx4 is deleted. In Gdf9cre; Tbx4(fl/-)
      and Zp3cre; Tbx4(fl/-) adult females, primordial, primary, secondary, and antral
      follicles form, ovulation occurs, corpus luteum formation is normal, and the mice
      are fertile without any evidence of diminished ovarian reserve. Although
      postnatal deletion of Tbx4 in oocytes does not obviously impair fertility, it is
      possible that the reduction in PGCs observed in Tbx4 homozygous null mutant
      embryos could affect long-term fertility in adults. 

PMID- 24089202
TI  - Granulosa cells from emerged antral follicles of the bovine ovary initiate
      inflammation in response to bacterial pathogen-associated molecular patterns via
      Toll-like receptor pathways.
AB  - Bacterial infections of the uterus or mammary gland commonly perturb ovarian
      antral follicle growth and function, causing infertility in cattle. Cells of the
      innate immune system use Toll-like receptors (TLRs) TLR2, TLR4, and TLR5 to
      recognize pathogen-associated molecular patterns (PAMPs) of bacteria, leading to
      production of inflammatory mediators, such as IL-1beta, IL-6, and IL-8. The
      present study examined whether granulosa cells from emerged antral follicles have
      functional responses to typical bacterial PAMPs. Granulosa cells from emerged
      bovine antral follicles expressed mRNA for all 10 TLRs. Cellular expression of
      mRNA for the cytokines IL1B, IL6, IL10, and TNF, and chemokines IL8 and CCL5,
      increased after treatment with synthetic bacterial lipoprotein binding TLR2,
      lipopolysaccharide binding TLR4, or flagellin binding TLR5. Supernatants of
      granulosa cells accumulated IL-1beta, IL-6, and IL-8 protein in a concentration
      dependent manner when treated with lipoprotein or lipopolysaccharide, but not
      flagellin. Accumulation of IL6 in response to lipoprotein and lipopolysaccharide
      was attenuated using siRNA targeting TLR2 and TLR4, respectively. Granulosa cells
      increased phosphorylation of mitogen-activated protein kinase (MAPK) 14 and
      MAPK3/1 within 30 min of treatment with lipopolysaccharide or lipoprotein, and
      inhibitors targeting MAPK14 reduced the accumulation of IL-6 in response to the
      PAMPs. Treatment with hormones follicle-stimulating hormone, luteinizing hormone,
      estradiol, or progesterone did not significantly affect granulosa cell responses
      to PAMPs. However, epidermal growth factor enhanced IL-6 accumulation in response
      to lipoprotein and inhibiting epidermal growth factor receptor (EGFR) abrogated
      the effect, whereas lipoprotein increased granulosa cell EGFR mRNA expression. In
      conclusion, bovine granulosa cells from emerged follicles sense bacterial PAMPs
      and initiate inflammatory responses via TLR2 and TLR4 pathways. 

PMID- 24089203
TI  - Variation in progesterone receptors and GnRH expression in the hypothalamus of
      the pregnant South American plains vizcacha, Lagostomus maximus (Mammalia,
      Rodentia).
AB  - In mammals, elevated levels of progesterone (P4) throughout gestation maintain a
      negative feedback over the hypothalamic-hypophyseal-gonadal (H-H-G) axis,
      avoiding preovulatory follicular growth and preventing ovulation. Recent studies
      showed that in the South American plains vizcacha (Lagostomus maximus)
      folliculogenesis progresses to preovulatory stages during gestation, and an
      ovulatory process seems to occur at midgestation. The aim of this work was to
      analyze hypothalamic gonadotropin-releasing hormone (GnRH) and P4 receptors (PR)
      expression and luteinizing hormone (LH) secretion and correlate these with the
      functional state of the ovary in nonovulating and ovulating females and gestating
      females with special emphasis in the supposedly ovulating females at
      midgestation. We investigated P4 and LH serum levels as well as the distribution,
      localization, and expression of PR and GnRH in the hypothalamus of L. maximus at
      different time points during gestation and in nongestating, ovulating and
      nonovulating, females. A significant increment in GnRH, P4, and LH was detected
      in midpregnant vizcachas with respect to early-pregnant and to ovulating females.
      PR was also significantly increased in midpregnant animals. PR was detected in
      neurons of the preoptic and hypothalamic areas. Coexistence of both PR and GnRH
      in neurons of medial preoptic area and supraoptic nucleus was detected.
      Midpregnant animals showed increased number of PR immunoreactive cells at median
      eminence, localized adjacently to GnRH immunoreactive fibers. High expression of
      hypothalamic GnRH and PR, despite an increased level of P4, was correlated with
      the presence of antral, preovulatory follicles, and luteinized unruptured
      follicles at midgestation that suggest a possible role of the H-H-G axis in the
      modulation of ovulation during gestation in L. maximus. 

PMID- 24089204
TI  - The disturbances of endoplasmic reticulum calcium homeostasis caused by increased
      intracellular reactive oxygen species contributes to fragmentation in aged
      porcine oocytes.
AB  - Accumulating evidence indicates that cellular and molecular abnormalities occur
      during oocyte aging, including fragmentation, increases in intracellular reactive
      oxygen species (ROS), and abnormal Ca(2+) oscillations. The objective of the
      present study was to characterize the relationships between intracellular ROS,
      Ca(2+) homeostasis of endoplasmic reticulum (ER), and fragmentation in aged
      porcine MII oocytes. Prolonged culture (36 h) of porcine oocytes resulted in
      elevated intracellular ROS level, impaired ER Ca(2+) homeostasis (i.e., Ca(2+)
      storage, Ca(2+) rising patterns after electroactivation, and the cluster
      distribution of ER), and increased fragmentation rates. However, when the porcine
      oocytes were treated with 1,2-bis(2-aminophenoxy)ethane-N,N,N',N'-tetraacetic
      acid tetrakis(acetoxymethyl ester), an intracellular Ca(2+) chelator, the
      fragmentation was significantly inhibited during in vitro aging. In order to
      pursue the underlying mechanisms, H2O2 and cycloheximide (CHX) were used to
      artificially increase or inhibit, respectively, the intracellular ROS levels in
      aged porcine oocytes during in vitro culture. The results demonstrated that
      incubation of porcine MII oocytes with H2O2 damaged the ER clusters and the
      Ca(2+) regulation of ER, leading to a high proportion of fragmented oocytes. In
      contrast, CHX, an intracellular inhibitor of ROS generation, prevented both
      increase of ROS level and damage of the ER Ca(2+) homeostasis in porcine oocytes
      during aging, resulting in low fragmentation rate. We conclude that the increased
      intracellular ROS damaged the ER clusters and ER Ca(2+) homeostasis, resulting in
      a disorder in ooplasmic free Ca(2+), which caused the fragmentations seen in
      porcine MII oocytes during aging. 

PMID- 24089205
TI  - Autophagy promotes primary ciliogenesis by removing OFD1 from centriolar
      satellites.
AB  - The primary cilium is a microtubule-based organelle that functions in sensory and
      signalling pathways. Defects in ciliogenesis can lead to a group of genetic
      syndromes known as ciliopathies. However, the regulatory mechanisms of primary
      ciliogenesis in normal and cancer cells are incompletely understood. Here we
      demonstrate that autophagic degradation of a ciliopathy protein, OFD1 (oral
      facial-digital syndrome 1), at centriolar satellites promotes primary cilium
      biogenesis. Autophagy is a catabolic pathway in which cytosol, damaged organelles
      and protein aggregates are engulfed in autophagosomes and delivered to lysosomes
      for destruction. We show that the population of OFD1 at the centriolar satellites
      is rapidly degraded by autophagy upon serum starvation. In autophagy-deficient
      Atg5 or Atg3 null mouse embryonic fibroblasts, OFD1 accumulates at centriolar
      satellites, leading to fewer and shorter primary cilia and a defective
      recruitment of BBS4 (Bardet-Biedl syndrome 4) to cilia. These defects are fully
      rescued by OFD1 partial knockdown that reduces the population of OFD1 at
      centriolar satellites. More strikingly, OFD1 depletion at centriolar satellites
      promotes cilia formation in both cycling cells and transformed breast cancer MCF7
      cells that normally do not form cilia. This work reveals that removal of OFD1 by
      autophagy at centriolar satellites represents a general mechanism to promote
      ciliogenesis in mammalian cells. These findings define a newly recognized role of
      autophagy in organelle biogenesis. 

PMID- 24089206
TI  - Cell biology: Molecular clearance at the cell's antenna.

PMID- 24089207
TI  - Cancer: Killing from the inside.

PMID- 24089208
TI  - A juvenile mouse pheromone inhibits sexual behaviour through the vomeronasal
      system.
AB  - Animals display a repertoire of different social behaviours. Appropriate
      behavioural responses depend on sensory input received during social
      interactions. In mice, social behaviour is driven by pheromones, chemical signals
      that encode information related to age, sex and physiological state. However,
      although mice show different social behaviours towards adults, juveniles and
      neonates, sensory cues that enable specific recognition of juvenile mice are
      unknown. Here we describe a juvenile pheromone produced by young mice before
      puberty, termed exocrine-gland secreting peptide 22 (ESP22). ESP22 is secreted
      from the lacrimal gland and released into tears of 2- to 3-week-old mice. Upon
      detection, ESP22 activates high-affinity sensory neurons in the vomeronasal
      organ, and downstream limbic neurons in the medial amygdala. Recombinant ESP22,
      painted on mice, exerts a powerful inhibitory effect on adult male mating
      behaviour, which is abolished in knockout mice lacking TRPC2, a key signalling
      component of the vomeronasal organ. Furthermore, knockout of TRPC2 or loss of
      ESP22 production results in increased sexual behaviour of adult males towards
      juveniles, and sexual responses towards ESP22-deficient juveniles are suppressed
      by ESP22 painting. Thus, we describe a pheromone of sexually immature mice that
      controls an innate social behaviour, a response pathway through the accessory
      olfactory system and a new role for vomeronasal organ signalling in inhibiting
      sexual behaviour towards young. These findings provide a molecular framework for
      understanding how a sensory system can regulate behaviour. 

PMID- 24089209
TI  - Functional interaction between autophagy and ciliogenesis.
AB  - Nutrient deprivation is a stimulus shared by both autophagy and the formation of
      primary cilia. The recently discovered role of primary cilia in nutrient sensing
      and signalling motivated us to explore the possible functional interactions
      between this signalling hub and autophagy. Here we show that part of the
      molecular machinery involved in ciliogenesis also participates in the early steps
      of the autophagic process. Signalling from the cilia, such as that from the
      Hedgehog pathway, induces autophagy by acting directly on essential autophagy
      related proteins strategically located in the base of the cilium by ciliary
      trafficking proteins. Whereas abrogation of ciliogenesis partially inhibits
      autophagy, blockage of autophagy enhances primary cilia growth and cilia
      associated signalling during normal nutritional conditions. We propose that basal
      autophagy regulates ciliary growth through the degradation of proteins required
      for intraflagellar transport. Compromised ability to activate the autophagic
      response may underlie some common ciliopathies. 

PMID- 24089210
TI  - Odour receptors and neurons for DEET and new insect repellents.
AB  - There are major impediments to finding improved DEET alternatives because the
      receptors causing olfactory repellency are unknown, and new chemicals require
      exorbitant costs to determine safety for human use. Here we identify DEET
      sensitive neurons in a pit-like structure in the Drosophila melanogaster antenna
      called the sacculus. They express a highly conserved receptor, Ir40a, and flies
      in which these neurons are silenced or Ir40a is knocked down lose avoidance to
      DEET. We used a computational structure-activity screen of >400,000 compounds
      that identified >100 natural compounds as candidate repellents. We tested several
      and found that most activate Ir40a(+) neurons and are repellents for Drosophila.
      These compounds are also strong repellents for mosquitoes. The candidates contain
      chemicals that do not dissolve plastic, are affordable and smell mildly like
      grapes, with three considered safe in human foods. Our findings pave the way to
      discover new generations of repellents that will help fight deadly insect-borne
      diseases worldwide. 

PMID- 24089211
TI  - Crystal structure of a Na+-bound Na+,K+-ATPase preceding the E1P state.
AB  - Na(+),K(+)-ATPase pumps three Na(+) ions out of cells in exchange for two K(+)
      taken up from the extracellular medium per ATP molecule hydrolysed, thereby
      establishing Na(+) and K(+) gradients across the membrane in all animal cells.
      These ion gradients are used in many fundamental processes, notably excitation of
      nerve cells. Here we describe 2.8 A-resolution crystal structures of this ATPase
      from pig kidney with bound Na(+), ADP and aluminium fluoride, a stable phosphate
      analogue, with and without oligomycin that promotes Na(+) occlusion. These
      crystal structures represent a transition state preceding the phosphorylated
      intermediate (E1P) in which three Na(+) ions are occluded. Details of the Na(+)
      binding sites show how this ATPase functions as a Na(+)-specific pump, rejecting
      K(+) and Ca(2+), even though its affinity for Na(+) is low (millimolar
      dissociation constant). A mechanism for sequential, cooperative Na(+) binding can
      now be formulated in atomic detail. 

PMID- 24089215
TI  - Surface molecularly imprinted polymers-based electrochemical sensor for bovine
      hemoglobin recognition.
AB  - A novel electrochemical sensor for bovine hemoglobin (BHb) recognition and
      detection was prepared by a surface molecularly imprinted technique. Aldehyde
      group-functionalized silica microspheres were modified on an Au electrode
      surface, and these were subsequently covalently bound with the template molecule,
      BHb, through imine bonds. Electropolymerization was performed to deposit
      polypyrrole onto the above modified electrode surface. A three-dimensional
      macroporous structural sensor was obtained after etching of silica and the
      extraction of BHb. Differential pulse voltammetry (DPV) and electrochemical
      impedance spectroscopy (EIS) were employed to characterize the fabrication
      process of the sensor using [Fe(CN)6](3-)/[Fe(CN)6](4-) as an electroactive
      probe. Since all imprinted cavities were situated at the surface of the polymers,
      the prepared sensor exhibited considerably fast binding kinetics. Compared to
      other non-template proteins, the sensor showed an excellent recognition capacity
      for BHb. Moreover, the prepared sensor also exhibited a dependent relationship
      between the concentration of BHb and the peak current of [Fe(CN)6](3
      )/[Fe(CN)6](4-). 

PMID- 24089214
TI  - Geometric control of cell migration.
AB  - Morphological polarization involving changes in cell shape and redistribution of
      cellular signaling machinery, initiate the migration of mammalian cells. Golgi
      complex typically localizes in front of the nucleus, and this frontwards
      polarization has been proposed to be involved in directional migration. However,
      the sequence of events remains unresolved. Does Golgi polarization precede
      directional migration or vice-versa? We address this question by constraining
      cells to specific areas and shapes then tracking their motile behavior and the
      spatio-temporal distribution of Golgi apparatus upon release. Results show that
      while the position of the Golgi complex depends on the cell geometry, the
      subcellular localization of the Golgi complex does not define the cell's leading
      edge. Cells constrained within elongated geometries exhibit polarized extension
      of lamellipodia and upon release, migrate preferentially along the long axis of
      the cell. Minimally constrained cells released from larger areas however, exhibit
      retarded migration regardless of lamellipodia protrusion activity. 

PMID- 24089213
TI  - Paneth cells as a site of origin for intestinal inflammation.
AB  - The recognition of autophagy related 16-like 1 (ATG16L1) as a genetic risk factor
      has exposed the critical role of autophagy in Crohn's disease. Homozygosity for
      the highly prevalent ATG16L1 risk allele, or murine hypomorphic (HM) activity,
      causes Paneth cell dysfunction. As Atg16l1(HM) mice do not develop spontaneous
      intestinal inflammation, the mechanism(s) by which ATG16L1 contributes to disease
      remains obscure. Deletion of the unfolded protein response (UPR) transcription
      factor X-box binding protein-1 (Xbp1) in intestinal epithelial cells, the human
      orthologue of which harbours rare inflammatory bowel disease risk variants,
      results in endoplasmic reticulum (ER) stress, Paneth cell impairment and
      spontaneous enteritis. Unresolved ER stress is a common feature of inflammatory
      bowel disease epithelium, and several genetic risk factors of Crohn's disease
      affect Paneth cells. Here we show that impairment in either UPR (Xbp1(DeltaIEC))
      or autophagy function (Atg16l1(DeltaIEC) or Atg7(DeltaIEC)) in intestinal
      epithelial cells results in each other's compensatory engagement, and severe
      spontaneous Crohn's-disease-like transmural ileitis if both mechanisms are
      compromised. Xbp1(DeltaIEC) mice show autophagosome formation in hypomorphic
      Paneth cells, which is linked to ER stress via protein kinase RNA-like
      endoplasmic reticulum kinase (PERK), elongation initiation factor 2alpha
      (eIF2alpha) and activating transcription factor 4 (ATF4). Ileitis is dependent on
      commensal microbiota and derives from increased intestinal epithelial cell death,
      inositol requiring enzyme 1alpha (IRE1alpha)-regulated NF-kappaB activation and
      tumour-necrosis factor signalling, which are synergistically increased when
      autophagy is deficient. ATG16L1 restrains IRE1alpha activity, and augmentation of
      autophagy in intestinal epithelial cells ameliorates ER stress-induced intestinal
      inflammation and eases NF-kappaB overactivation and intestinal epithelial cell
      death. ER stress, autophagy induction and spontaneous ileitis emerge from Paneth
      cell-specific deletion of Xbp1. Genetically and environmentally controlled UPR
      function within Paneth cells may therefore set the threshold for the development
      of intestinal inflammation upon hypomorphic ATG16L1 function and implicate ileal
      Crohn's disease as a specific disorder of Paneth cells. 

PMID- 24089216
TI  - Helicity discrimination in N,N'-dibenzoyl-1,2,3,4,7,8,9,10-octahydro-1,10
      phenanthrolines and their thiono- and selenocarbonyl analogues by inclusion
      complexation with chiral diols.
AB  - X-ray crystallographic analysis of the title compounds revealed that they assume
      a folded helical conformation of an approximate C2 symmetry in the solid state.
      Dithioamide 5b, diselenoamide 5c and monoselenoamide 5d were resolved to
      enantiomers by inclusion crystallization with optically active diols (TADDOLs).
      The absolute configuration of the guest molecules in the complexes 5b.6a, 5c.6a
      and 5d.6a was assigned as P. The optical activity of the resolved compounds is
      manifested by their CD spectra showing relatively strong Cotton effects in the
      region of thionoamide and selenoamide n-pi* transition. The optically active
      thiono- and selenoamides are configurationally labile compounds and gradually
      racemize in solution but they are stable in the form of the inclusion complexes.
      The first-order kinetics of the racemization in solution allowed us to assign the
      racemization barriers by the spectropolarimetric measurements.

PMID- 24089217
TI  - Bone disease in the setting of HIV infection: update and review of the
      literature.
AB  - The advent of highly active antiretroviral therapy (HAART) in the mid-1990s has
      transformed Human Immunodeficiency Virus (HIV) infection into a chronic disease.
      HIV-infected patients are living longer and are facing several non-AIDS
      associated morbidities related with aging, including diabetes mellitus,
      cardiovascular disease, osteoporosis, osteopenia and fragility fractures. The
      prevalence of bone disease is higher among HIV-infected subjects. In addition to
      traditional risk factors, HAART, chronic inflammation and the virus itself have
      been suggested to contribute to bone loss in the setting of HIV infection. In the
      present review, we summarize the current knowledge about risk factors for low
      bone mineral density in HIV-positive patients as well as current recommendations
      for fracture screening and treatment in this specific population. 

PMID- 24089218
TI  - Membrane microparticles and diseases.
AB  - Membrane microparticles (MPs) are plasma membrane-derived vesicles shed by
      various types of activated or apoptotic cells including platelets, monocytes,
      endothelial cells, red blood cells, and granulocytes. MPs are being increasingly
      recognized as important regulators of cell-to-cell interactions. Recent evidences
      suggest they may play important functions not only in homeostasis but also in the
      pathogenesis of a number of diseases such as vascular diseases, cancer,
      infectious diseases and diabetes mellitus. Accordingly, inhibiting the production
      of MPs may serve as a novel therapeutic strategy for these diseases. Here we
      review recent advances on the mechanism underlying the generation of MPs and the
      role of MPs in vascular diseases, cancer, diabetes, inflammation, and pathogen
      infection. 

PMID- 24089219
TI  - Evaluation of the olfactory memory after spinal anesthesia: a pilot study.
AB  - BACKGROUND: The aim of this study was to investigate the effect of spinal
      anesthesia (SA) on olfactory memory using Brief-Smell Identification TestTM (B
      SIT). PATIENTS AND METHODS: This, prospective, clinical study was performed on 40
      ASA physical status I-III patients, between 18-65 years of age undergoing a
      planned elective minor surgery under SA. All participants were preoperatively
      informed about B-SIT and the mode of application of the test according to the
      information in the book. B-SIT was applied to each patient preoperatively and the
      scores were recorded. B-SIT was reapplied to all patients on the 1st and 2nd
      postoperative days and the scores were recorded. Moreover, development of
      postdural puncture headache (PDPH) and/or neurological symptoms (such as hearing
      loss, diplopia) were checked. RESULTS: Postoperative headache was observed in 7
      of the participants and 3 of them was diagnosed to have PDPH. No statistically
      significant difference was observed in the olfactory memory evaluation of the
      patients suffering from headache and the 3 patients diagnosed with PDPH. No
      statistically significant difference was observed in the correct odor answer
      ratio between the preoperative and postoperative 1st and 2nd days (p > 0.05).
      CONCLUSIONS: We confirm that SA does not affect olfactory memory. Further studies
      are necessary to confirm the results of our pilot study in a larger sample.

PMID- 24089220
TI  - Something more to say about calcium homeostasis: the role of vitamin K2 in
      vascular calcification and osteoporosis.
AB  - BACKGROUND: Vascular calcification and osteoporosis share similar
      etiopathogenetic mechanisms. Vitamin K2 deficiency could be responsible of the so
      called "calcium paradox", that is the lack of calcium in the bone and its storage
      in the vessel wall. These events may have clinically relevant consequences, such
      as cardiovascular accidents, and bone fractures. AIM: To review the biological
      function of vitamin K2 metabolism, the main factors related to its deficiency and
      the consequent clinical significance. DISCUSSION: Vitamin K2 is essential for the
      function of several proteins, involved in the maintenance of the normal structure
      of arterial wall, osteoarticular system, teeth, and for the regulation of cell
      growth. It has been demonstrated to have a pivotal role in the inhibition of
      vascular foci of calcification, and in the regulation of calcium deposition in
      the bone. Vitamin K2 deficiency is often subclinic in a large part of healthy
      population. This deficiency is related to the interaction of various factors,
      such as the reduced dietary intake, the alteration of intestinal absorption or
      production, with a possible role of intestinal microbiota and the increased
      consumption at the vessel wall. CONCLUSIONS: Vitamin K2 deficiency has recently
      been recognized as a protagonist in the development of vascular calcification and
      osteoporosis. Data reported so far are promising and, dietary supplementation
      seems a useful tool to contrast these diseases. However, large studies or solid
      clinical correlations regarding vitamin K2 deficiency and its pathologic
      consequences are needed to confirm these preliminary experiences.

PMID- 24089221
TI  - Bioinformatic analysis of microarray data reveals several key genes related to
      heart failure.
AB  - OBJECTIVES: Heart failure is a major public health problem worldwide. However,
      the molecular mechanism is still unclear. This study aims to discover
      differentially expressed genes (DEGs) between non-ischemic or ischemic heart
      failure samples and healthy control, which may be used for diagnosis and
      treatment of heart failure. MATERIALS AND METHODS: Gene expression profile
      GSE9128 was downloaded from Gene Expression Omnibus, including 3 normal samples,
      4 non-ischemic heart failure samples and 4 ischemic samples. Data processing and
      differential analysis were carried out with packages of R. Cluster analysis was
      also performed for all the samples to globally observe the difference among the
      three groups of samples. Interactors of the DEGs were retrieved with Osprey and
      then networks were constructed. The overlapping part of the network was selected
      out using Cytoscape, for which functional enrichment analysis was applied with
      DAVID tools. RESULTS: A total of 293 and 133 DEGs were obtained for non-ischemic
      and ischemic heart failure, respectively. Two networks were established and then
      functional enrichment analysis revealed that "regulation of programmed cell
      death" was most significantly over-represented in common DEGs. CONCLUSIONS: Genes
      differentially expressed in non-ischemic and ischemic heart failure can be
      biomarkers to distinguish the two types of heart failure. Besides, these genes
      can be targets to develop treatments.

PMID- 24089222
TI  - Blood pressure reducing effects of piromelatine and melatonin in spontaneously
      hypertensive rats.
AB  - BACKGROUND: Recently, widespread interest has grown regarding melatonin treatment
      of hypertension including its cardioprotective effects. Studies in rodents
      indicate that melatonin plays a role in the pathogenesis of hypertension in rats
      with metabolic syndrome. Piromelatine, a melatonin agonist, serotonin 5-HT-1A and
      5-HT-1D agonist and serotonin 5-HT2B antagonist is a multimodal agent with sleep
      promoting, anti-diabetic, analgesic, anti-neurodegenerative, anxiolytic and
      antidepressant potential, currently in development for the treatment of insomnia.
      AIM: In this report we assessed the effects of piromelatine and melatonin
      treatment on blood pressure in spontaneously hypertensive rats (SHR) and
      normotensive Wistar-Kyoto (WKY) rats. MATERIALS AND METHODS: Five groups of 12-wk
      old rats (10/group) were treated for 5 weeks with a vehicle, piromelatine (5, 15
      and 50 mg/kg BW) and melatonin (10 mg/kg BW) and an age-matched WKY control
      group. Systolic blood pressure (tail-cuff method) was measured weekly at 9:00
      a.m. and at 9:00 p.m. The rats body weight, plasma glucose, insulin,
      triglyceride, adiponectin, total cholesterol, HDL and LDL/VLDL cholesterol were
      also measured. RESULTS: Our results showed that both piromelatine and melatonin
      reduced SHR blood pressure significantly both during the morning and the evening.
      Piromelatine, but not melatonin, also reduced SHR body weight gain and both
      significantly decreased plasma glucose and insulin levels and increased
      adiponectin levels. CONCLUSIONS: Piromelatine, similar to melatonin, has an
      antihypertensive effect and also attenuates body weight, improves metabolic
      profiles and might be useful in the treatment of hypertension and the metabolic
      syndrome.

PMID- 24089223
TI  - Giant aneurysm of the right coronary artery with fistula to right atrium.
AB  - Coronary artery aneurysms are rare entities with a prevalence of 0.15%-4.9%.
      Giant coronary artery aneurysms are known as more than 2 to 5 cm in size. We
      present a case of 74 year-old female who was admitted to our clinic with chest
      pain and dyspnea. Coronary angiography demonstrated a giant right coronary artery
      (RCA) aneurysm with a significant left-to-right shunt. The patient underwent an
      open heart surgery. During the exploration, an aneurysm of 40 mm in diameter of
      the RCA was seen. The aneurysmatic RCA was excluded and continuously closed with
      the support of intra-aortic balloon pump (IABP). The patient was discharged on
      the 13th postoperative day without any complication. 

PMID- 24089224
TI  - 1:4 matched case-control study on influential factor of early onset neonatal
      sepsis.
AB  - BACKGROUND: Bacteria, funghi, viruses and protozoa can lead to neonatal sepsis.
      Neonatal sepsis is the leading cause of infectious disease onset and death in
      many neonates. AIM: To explore the major risk factors of early-onset neonatal
      sepsis and provide a scientific basis for strategies of early-onset neonatal
      sepsis prevention. SUBJECTS AND METHODS: A 1:4 matched case-control study was
      adopted and 147 cases of early-onset neonatal sepsis were enrolled. Conditional
      logistic regression model was used to analyze the univariate and multivariate
      data to estimate the odds ratio (OR) and the 95% confidence interval (95% CI).
      RESULTS: Univariate analysis shows that the impact factors on the occurrence of
      early-onset neonatal sepsis include the following: Maternal age > 35, mother
      having fixed occupation, mother of urban residence, abnormal fetal position,
      fetal times, parity, caesarean section, premature rupture of membranes, amniotic
      fluid volume abnormalities, pregnancy-induced hypertension, placental
      abnormalities, fetal distress, newborn gender, low birth weight infants, neonatal
      Apgar scoring at one and five minutes, neonatal jaundice, wet lung, anemia, IVH,
      and premature infant. Multivariate logistic regression analysis showed that
      maternal age > 35 (OR = 4.835, OR 95% CI = 1.170-19.981), cesarean section (OR =
      0.103, OR 95% CI = 0.041-0.258), premature rupture of membranes (OR = 0.207, OR
      95% CI = 0.078-0.547), premature infants (OR = 0.059, OR 95% CI = 0.010-0.329)
      and newborn jaundice (OR = 0.092, OR 95% CI = 0.021-0.404) were the factors of
      early-onset neonatal sepsis. CONCLUSIONS: Early-onset neonatal sepsis could be
      affected by multi-factors, and targeted prevention may reduce the incidence of
      early-onset neonatal sepsis rates.

PMID- 24089225
TI  - Comparison of tenofovir and entecavir in patients with chronic HBV infection.
AB  - BACKGROUND: Sustained suppression of serum HBV DNA levels with nucleos(t)ide
      analogues is the most important success obtained in the treatment of chronic HBV
      infection today. Tenofovir and entecavir provide more robust viral suppression.
      AIM: The aim of this study is to compare tenofovir and entecavir in terms of
      viral kinetics, side effects and virological response in patients with chronic
      HBV infection. PATIENTS AND METHODS: Patients with chronic hepatitis B treated
      with tenofovir or entecavir were included in this retrospective study. Using
      survey analysis, we evaluated independent variables reflecting virological
      response to treatment and determined whether use of tenofovir or entecavir was
      one of them. We compared the decline in serum HBV DNA levels at the 3rd, 6th,
      12th, 18th and 24th months of treatment between two groups. We also compared
      entecavir and tenofovir in terms of side effect rates. RESULTS: 117 patients
      [average age: 44 (20-73), 65 males (55.6%), 30 HBeAg positive (25.6%)] were
      enrolled in the study. Sixty-six patients (56.4%) used tenofovir and 51 (43.6%)
      patients used entecavir. Virological response was better in patients using
      tenofovir (Odd's ratio of 1.796 and p = 0.014) and having high fibrosis score
      (Odd's ratio of 0.182 and p = 0.018). Entecavir was more effective in reducing
      serum HBV DNA levels at the 3rd month of treatment (serum HBV DNA decline of 4.45
      and 3.96 log10 units for entecavir and tenofovir respectively, p = 0.031), but
      decline rates were similar at other months. There was no difference between
      patient groups in terms of side effects and discontinuation of treatment due to
      side effects. CONCLUSIONS: Patients with chronic HBV infection using tenofovir
      have better virological response than those using entecavir.

PMID- 24089226
TI  - Intrahepatic IFN-alpha expression in liver specimens from HBV-infected patients
      with different outcomes.
AB  - BACKGROUND: Interferon-alpha (IFN-alpha), an active cytokine, plays an important
      role in antiviral host responses, including protection against hepatitis B virus
      (HBV) infection. This study was designed to investigate the correlation between
      intrahepatic IFN-alpha expression levels and disease severity using liver biopsy
      specimens from HBV-infected patients with different outcomes. PATIENTS AND
      METHODS: Immunohistochemistry (IHC) was performed to detect intrahepatic IFN
      alpha expression in liver biopsy specimens obtained from 69 HBV-infected patients
      with different outcomes (including 23 cases with chronic hepatitis B [CHB], 18
      cases with severe hepatitis B [SHB], and 28 cases with liver cirrhosis [LC]). In
      situ hybridization (ISH) was carried out to measure the levels of HBV DNA in
      liver samples. In addition, the liver specimens of 33 healthy liver transplant
      donors without detectable liver diseases comprised a normal control (NC) group.
      RESULTS: The intrahepatic expression levels of IFN-alpha were higher in the HBV
      infected patients than the NC group (p = 0.001). Intrahepatic IFN-alpha
      expression was also significantly higher in the SHB and CHB groups compared to
      the NC group (p = 0.001 and p = 0.001, respectively), while the intrahepatic HBV
      DNA levels of the SHB patients were higher than those of LC patients (p = 0.013).
      Furthermore, intrahepatic IFN-alpha expression was positively correlated with
      serum alanine aminotransferase (ALT) levels in CHB patients; no significant
      correlations were discovered between intrahepatic IFN-alpha expression and
      intrahepatic HBV DNA levels in all other sub-groups. CONCLUSIONS: Intrahepatic
      IFN-alpha expression may correlate with liver inflammation after hepatitis B
      virus infection, and IFN-alpha may play a vital role in the occurrence of SHB.

PMID- 24089227
TI  - Effect of microbiological and immunological enteral nutrition on intestinal
      function and immune status in the patients with long-term use of antibiotics.
AB  - BACKGROUND: To investigate the effect of microbiological and immunological
      enteral nutrition (MEIN composed by probiotics, L-Glutamide, deep-sea fish oil
      and Nutrison Fibre) on intestinal function and immune status in the patients with
      long-term use of antibiotics. PATIENTS AND METHODS: 56 severe apoplexy patients
      with pulmonary infectious complication were randomly divided into two groups: a
      microbiological and immunological enteral nutrition group (MEIN group, n=28) and
      an enteral nutrition group (EN group, n=28). MEIN suspension (Live Combined
      Bifidobacterium, L-Glutamide, deep-sea fish oil and Nutrison Fibre) and ordinary
      enteral nutrition liquid (Nutrison Fibre) were given to patients of the MEIN
      group and EN group respectively for at least for 20 days. Then the trophonemata,
      incidence rates of abdominal pain, abdominal distention and diarrhea, tolerance
      and immunologic parameters including CD4+, CD8+ T-lymphocyte percentage,
      CD4+/CD8+ ratio and NK cells in peripheral blood were estimated and compared
      between the two groups during the period of nutritional support. RESULTS: No
      statistical difference was observed in trophonemata between the two groups (p >
      0.05). The abdominal pain and abdominal distension incidence rates of the
      patients in MEIN group were significantly lower than those of patients in EN
      group. (7.2% vs 32.1%, 14.2% vs 39.3%, 0% vs 10.7%) (p < 0.05). There was a
      significantly better tolerance in MEIN group compared to EN group after treatment
      (p < 0.05). In addition, the levels of immune parameters of the patients in MEIN
      group were much higher compared to that of those in EN group on the 20th day
      after grouping (p < 0.05). CONCLUSIONS: Compared with the general formula EN,
      MEIN is more helpful for the patients with Long-term use of antibiotics in
      improving intestinal function and cellular immune function.

PMID- 24089228
TI  - Propofol suppresses proliferation, invasion and angiogenesis by down-regulating
      ERK-VEGF/MMP-9 signaling in Eca-109 esophageal squamous cell carcinoma cells.
AB  - BACKGROUND AND AIMS: Propofol (2,6-diisopropylphenol), one of the most commonly
      used intravenous anaesthetic agents during cancer resection surgery, has been
      reported to have the ability of influencing the invasion of human cancer cells.
      However, the mechanisms are not very clear. In this study, we investigated the
      effects of propofol on the proliferation, invasion and angiogenesis of human Eca
      109 cells, and explored the mechanism. METHODS: The human Eca-109 cells was
      treated with propofol at the concentrations of 10-100 umol/L for 72 hours or at
      the concentration of 100 umol for 8-72 hours. Cell viability was determined by
      the MTT assay; the effect of propofol on apoptosis by 5'-triphosphate-biotin nick
      end labeling (TUNEL) staining. The effect of propofol on angiogenesis was
      determined by the chicken chorioallantoic membrane (CAM) angiogenesis assay. The
      effect of propofol on cell invasion using a modified Matrigel Boyden chamber
      assay. ERK1/2, MMP-9 and VEGF leves was detected by western blotting assay.
      RESULTS: In human Eca-109 cells, propofol significantly promoted cell apoptosis
      and inhibited proliferation in a dose and time-dependent manner. Furthermore,
      propofol inhibited dose and time-dependent invasion and angiogenesis. Propofol
      significantly dose and time-dependently down-regulated gene expression and
      protein production of ERK/pERK, VEGF and MMP-9. The functional effects and MMP
      9/VEGF inhibition were shown to be dependent on the ERK/VEGF and ERK/MMP-9
      signaling pathways. It was noteworthy that the ERK activator (phorbol 12
      myristate 13-acetate [PMA]) treatment increased the MMP-9/VEGF levels after
      propofol treatment, and led to significant increase of proliferation, invasion
      and angiogenesis. CONCLUSIONS: These findings indicate that propofol inhibited
      proliferation, invasion and angiogenesis of human Eca-109 cells in vitro through
      modulation of ERK-VEGF /MMP-9 signaling. Propofol not only can be an anesthesia
      agent which reduces pain but plays an important role of inhibiting the migration
      and angiogenesis of ESCC cells in the therapy of ESCC patients.

PMID- 24089229
TI  - First case of transformation for breast fibroadenoma to high-grade malignant
      phyllodes tumor in an in vitro fertilization patient: misdiagnosis of recurrence,
      treatment and review of the literature.
AB  - INTRODUCTION: Cystosarcoma phyllodes are very rare tumors and may be difficult to
      diagnose clinically. BACKGROUND: Fibroadenomas have long been considered benign
      hyperplastic lesions rather than true neoplastic processes. However, previous
      clonality studies have shown differing results. AIM: to assess diagnostic and
      treatment options for phyllodes tumor. MATERIALS AND METHODS: A 41-year-old
      female patient undergoing assisted fertilization treatment. The patient underwent
      fine needle aspiration biopsy that confirmed fibroadenoma before the IVF attempt.
      At 17 weeks of gestation, due to an increase in volume of the fibroadenoma, an
      excisional biopsy was performer that showed a malignant phyllodes tumor. Then she
      underwent quadrantectomy and chemiotherapy After 1 year there was a recurrence of
      phyllodes tumors and she underwent mastectomy and chemotherapy. RESULTS:
      Fibroadenoma that was transformed into high-grade malignant cystosarcoma after
      ovarian stimulation, relapsed after one year and it was not immediately
      diagnosed. The patient underwent mastectomy and chemotherapy. DISCUSSION: it is
      difficult to diagnose recurrence and to determine tele frequency and the right
      treatment for such a rare cancer, so it is important to report any case in the
      literature. CONCLUSIONS: We recommend to remove a fibroadenoma before attempting
      IVF for the risk of malignant transformation.

PMID- 24089230
TI  - Change of selenium in environment and risk of adolescent idiopathic scoliosis: a
      retrospective cohort study.
AB  - OBJECTIVES: Scoliosis is the disease which has a long history over one century.
      However, the pathogenesis remains unclear at present. To demonstrate the effect
      of different selenium content in environment on the morbidity of adolescent
      idiopathic scoliosis (AIS). METHODS: Retrospective cohort study (follow-up from
      1997 to 2009): compare the difference morbidity between high selenium group and
      the normal selenium group of AIS. PATIENTS: 9998 cases from three areas in China
      were participated in this study. There is different selenium content in these
      three areas. RESULTS: High selenium levels were significant associated with the
      AIS morbidity. While low selenium level had no significant correlation with the
      AIS morbidity. CONCLUSIONS: This study confirmed that high selenium content in
      the environment was one of risk factors for idiopathic scoliosis. We speculated
      that the excessive growth of the spine and the spinal cord asynchronous growth
      effect were key factors that high selenium content in the environment leads to
      scoliosis.

PMID- 24089231
TI  - Regulation different network analysis of rheumatoid arthritis (RA) and
      osteoarthritis (OA).
AB  - BACKGROUND: Rheumatoid arthritis (RA) is a systemic autoimmune disease
      characterized by chronic synovitis that progresses to destruction of cartilage
      and bone. AIM: The purpose of this study was to employ microarray analysis
      combined with bioinformatics techniques to evaluate differential gene expression
      in BM-derived mononuclear cells obtained from patients with rheumatoid arthritis
      (RA) or osteoarthritis (OA) to study the pathogenesis of this disease. MATERIALS
      AND METHODS: Gene expression profiles in BM-derived mononuclear cells from 9 RA
      and 10 OA patients were obtained from GEO. RESULTS: The bone marrow (BM)
      mononuclear cells showed 2581 up-regulated and 649 down-regulated genes in RA
      patients relative to the OA group: Our analysis indicated that several
      differentially expressed genes might play crucial roles in RA development,
      including SP1, RARA, ETS1, ETS2, FOS and ESR1. CONCLUSIONS: Further analysis
      predicted these genes might be involved in RA through cancer related pathways and
      immunity related pathways. Furthermore, these genes may serve as novel
      therapeutic targets for the treatment of RA.

PMID- 24089232
TI  - The effects of long term fasting in Ramadan on glucose regulation in type 2
      diabetes mellitus.
AB  - INTRODUCTION: For Ramadan fasting, observing Muslims do not eat or drink between
      sunrise and sunset during Ramadan, Islam's holy month of the year according to
      the lunar calendar. In 2011, fasting patients with diabetes fasted for an average
      of 16.5 hours per day, having 2 meals between sunset and sunrise for a month. We
      aimed to evaluate the impact of extended fasting on glucose regulation and
      observe possible complications of extended fasting in type 2 diabetes mellitus
      patients. PATIENTS AND METHODS: We conducted a randomized, retrospective,
      observational study. Patients who presented at the Diabetes Clinic during the 15
      days before and after Ramadan in August 2011 Istanbul, whose hemoglobin A1c,
      fasting plasma glucose, postprandial plasma glucose, weight and height value
      examinations and follow-up were completed were included in the study. FINDINGS:
      Seventy-six diabetes patients who fasted during Ramadan (fasting group) and 71
      patients with diabetes who did not fast (non-fasting group) were included in the
      study. These two groups with similar demographic characteristics were compared
      before and after Ramadan. HbA1c, fasting and postprandial plasma glucose, body
      mass index, weight and adverse events were evaluated. No statistically
      significant difference was observed among the fasting and the non-fasting groups.
      There was no difference between the pre and post-Ramadan values of the fasting
      group. CONCLUSIONS: We could not find any negative effects of extended fasting on
      glucose regulation of patients with diabetes who are using certain medications.
      No serious adverse event was observed. We failed to demonstrate benefits of
      increasing the number of meals in patients with diabetes.

PMID- 24089233
TI  - Serum paraoxonase, arylesterase activities and oxidative status in patients with
      insomnia.
AB  - AIM: The aim of this study was to investigate serum paraoxonase (PON) activity,
      arylesterase (ARE) activity, total antioxidant status (TAS), total oxidant status
      (TOS) and oxidative stress index (OSI) levels in patients with insomnia and to
      determine whether there was a relationship between oxidative stress and insomnia.
      PATIENTS AND METHODS: A total of 29 insomniacs and 25 healthy controls were
      recruited in this study. Serum PON and ARE activities, TAS and TOS level were
      determined, and OSI were calculated. RESULTS: Patients with insomnia had lower
      PON and ARE activities as compared to healthy controls (PON: 82.0+/-30.0 U/L vs.
      193.5+/-58.4 U/L, p < 0.001; ARE: 143.0+/-26.7 U/L vs. 175.0+/-27.1 U/L, p <
      0.001; respectively). Serum TAS was lower, while TOS and OSI were higher in the
      insomnia group than in the control group (TAS: 1.13+/-0.29 mmol Trolox
      equivalent/L vs. 1.70+/-0.35 mmol Trolox equivalent /L, p < 0.001; TOS: 18.68+/
      5.03 umol H2O2 equivalent/L vs. 10.92+/-2.21 umol H2O2 equivalent/L, p < 0.001;
      OSI: 1.76+/-0.74 vs. 0.68+/-0.23, p < 0.001; respectively). CONCLUSIONS: Patients
      with insomnia have increased systemic oxidative stress and reduced levels of
      serum antioxidant enzymes. Oxidative stress appears to be an underlying condition
      associated with insomnia.

PMID- 24089234
TI  - Indications for intraoperative frozen section in robot assisted radical
      prostatectomy: a pilot study.
AB  - INTRODUCTION: To evaluate indications for intraoperative frozen section (IFS)
      during robot assisted laparoscopic radical prostatectomy (RALRP) in our series.
      PATIENTS AND METHODS: Prospectively documented 80 patients with prostate cancer
      (PCa) who underwent RALRP were evaluated between June 2010 and July 2012.
      Patients were divided into 2 groups according to whether systematically IFS was
      performed or not. Group 1 (n=66) consisted of patients on whom systematic IFS was
      performed, Group 2 (n=14) consisted of patients on whom IFS was not performed.
      All recorded data evaluated and statistical analyses were performed for
      determining indications and predictive factors for IFS during RALRP. All patients
      were operated by single surgeon and IFS, pathological assessments were performed
      by experienced uro-pathologist. Statistical significant p value was p < 0.05.
      RESULTS: Mean follow-up was 15+/-6 (25-4) months. Pre-operative prostate volume
      in trans- rectal ultrasonography (TRUS) was statistically higher in Group 1 than
      Group 2 (p = 0.037). The other parameters were statistically similar in both
      groups. According to outcomes of our study IFS was a dependent factor for
      positive surgical margin. Additionally, the cut off value of prostate volume in
      TRUS for IFS was 55.5 cc for IFS. CONCLUSIONS: Preoperative measured prostate
      volume in TRUS may be an indicator of IFS. Therefore, more accurate information
      may be given to patients with prostate cancer (Pca) before RALRP by using
      preoperative prostate volume in TRUS.

PMID- 24089235
TI  - Association of calcium channel blocker use with lower hemoglobin levels in
      chronic kidney disease.
AB  - AIM: To search whether calcium channel blockers (CCBs) are associated with lower
      hemoglobin levels in chronic kidney disease (CKD) patients who are not on renal
      replacement therapy (RRT), vitamin D and anti-anemic treatment. PATIENTS AND
      METHODS: CKD patients were classified into two groups. Patients on CCBs treatment
      (103 patients) and patients not using CCBs (104 patients) were compared cross
      sectionally regarding clinical findings, complete blood count (CBC), biochemistry
      and regular medication use. Patients with polycystic kidney disease,
      comorbidities that could influence CBC other than iron deficiency of obscure
      origin, patients receiving RRT, erythropoietin (EPO), vitamin D, phosphate
      binders and drugs that could influence CBC were excluded. Under dependent
      variable of CCB use, all significantly different independent variables were
      subjected to multivariate binary logistic regression analysis (MBLRA). RESULTS:
      Lower hemoglobin, lower bilirubinemia, higher serum EPO, higher systolic blood
      pressure were observed in CCB users. Two groups were similar concerning age,
      gender, BMI, CKD etiology, CKD stage, pretibial edema prevalence, cardiothoracic
      index, diastolic blood pressure, corrected reticulocyte count, BUN, creatinine,
      eGFR, proBNP, parathormone, alkaline phosphatase, phosphorous, corrected
      calcemia, sCRP, relative EPO deficiency and prevalence of relative EPO deficient
      patients. Groups were comparable regarding comorbidities, types and usage
      frequencies of all antihypertensive medications other than CCBs. Higher systolic
      blood pressure and lower hemoglobin were significantly associated with CCB use
      after MBLRA. CONCLUSIONS: Hemoglobin was significantly lower in CCB users
      compared to non-users, among CKD patients who did not receive RRT, EPO, phosphate
      binders, vitamin D, iron, vitamin B12 and folic acid.

PMID- 24089236
TI  - Daily and annually variation of unstimulated whole saliva flow rate and pH and
      their relation with body profile in healthy young adults.
AB  - AIM: To analyse pH and flow rate (FR) of unstimulated whole saliva (UWS),
      detecting their possible correlations both among themselves and with body
      profile; in addition to identify daily, annually and gender differences.
      MATERIALS AND METHODS: Eighty-one (47 ?; 34 ?) healthy young adults (mean age
      22.7+/-4.09 years old) were enrolled. Saliva was sampled using spitting method.
      The data were statistically analysed using Pearson's coefficient, ANOVA or
      Kruskal-Wallis test, Student's t test or the Wilcoxon-Mann-Whitney test. RESULTS:
      The mean UWS/FR was 0.643 ml/min (range 0.164-1.656 ml/min; percentile 25 = 0.400
      ml/min; percentile 50 = 0.643 ml/min, percentile 75 = 0.832 ml/min; median =
      0.590 ml/min) and no significant differences were found in gender. The mean
      UWS/pH was 6.95 (range 6.06-7.91, S.D. 0.28, RSD % 4.08): pH was higher in males
      (7.02) than females (6.92; p = 0.009). The UWS/FR increased almost steadily
      during the day: from 0.593 ml/min at 9:00 to 0.669 ml/min at 17:00 (p = 0.04),
      the greatest increase was found between 9:00 and 11:00. Through the seasons the
      UWS/FR decreased from summer to spring with a difference of 0.048 ml/min (p <
      0.05). The UWS/pH showed a slight increase between 9:00 and 17:00 (p < 0.05).
      There were little differences in UWS/pH among the seasons (max. 0.09; p < 0.05).
      Only a significant correlation between UWS/FR and pH was found (R = 0.20; p =
      0.008). CONCLUSIONS: We did not find correlations between body profile vs UWS/FR
      or pH. UWS/FR varies more widely than UWS/pH: maintaining a proper acid/base
      balance is an essential factor for the homeostasis of the oral cavity and
      probably this would explain the reason for the lack of the variables evaluated
      influencing UWS/pH.

PMID- 24089237
TI  - A giant hemorragic adrenal pseudocyst: contrast-enhanced examination (CEUS) and
      computed tomography (CT) features.
AB  - INTRODUCTION: Adrenal pseudocysts are rare cystic masses that arise from the
      adrenal gland and which are usually non-functional and asymptomatic. We report a
      rare case of a giant hemorrhagic adrenal pseudocyst presenting with abdominal
      pain and we discussed the radiological features. PRESENTATION OF CASE: A 75 year
      old man was admitted with acute abdominal pain post mild-trauma. Computed
      tomography (CT) of abdomen revealed a hemorrhagic mass measuring 18 cm located in
      the right suprarenal region, displacing the right kidney and liver. He
      subsequently underwent to contrast enhancement ultrasound (CEUS), which showed
      features suggestive for hemorrhagic adrenal pseudocyst. A complete endocrine
      working didn't show any hormonal hypersecretion. The patient underwent laparotomy
      and right adrenal mass was excised. Histological examination revealed giant
      hemorrhagic adrenal pseudocyst. The abdominal pain resolved after surgery.
      CONCLUSIONS: to the best our knowledge, this is the first case studied with CEUS
      reported in the literature.

PMID- 24089238
TI  - Left descending coronary artery arising from anomalous distal circumflex coronary
      artery: a previously unreported coronary artery anomaly.

PMID- 24089239
TI  - Determining the effects of adrenaline and desflurane on QTc interval.

PMID- 24089240
TI  - Some marginal considerations about both preventive and therapeutic measures
      towards intestinal fibrosis in IBD.

PMID- 24089241
TI  - Reasons for the persistence of adverse events in the era of safer surgery--a
      qualitative approach.
AB  - OBJECTIVE: We sought to evaluate potential reasons given by board-certified
      doctors for the persistence of adverse events despite efforts to improve patient
      safety in Switzerland. SUMMARY BACKGROUND DATA: In recent years, substantial
      efforts have been made to improve patient safety by introducing surgical safety
      checklists to standardise surgeries and team procedures. Still, a high number of
      adverse events remain. METHODS: Clinic directors in operative medicine in
      Switzerland were asked to answer two questions concerning the reasons for
      persistence of adverse events, and the advantages and disadvantages of
      introducing and implementing surgical safety checklists. Of 799 clinic directors,
      the arguments of 237 (29.7%) were content-analysed using Mayring's content
      analysis method, resulting in 12 different categories. RESULTS: Potential reasons
      for the persistence of adverse events were mainly seen as being related to the
      "individual" (126/237, 53.2%), but directors of high-volume clinics identified
      factors related to the "group and interactions" significantly more often as a
      reason (60.2% vs 40.2%; p = 0.003). Surgical safety checklists were thought to
      have positive effects on the "organisational level" (47/237, 19.8%), the "team
      level" (37/237, 15.6%) and the "patient level" (40/237, 16.9%), with a "lack of
      willingness to implement checklists" as the main disadvantage (34/237, 14.3%).
      CONCLUSION: This qualitative study revealed the individual as the main player in
      the persistence of adverse events. Working conditions should be optimised to
      minimise interface problems in the case of cross-covering of patients, to assure
      support for students, residents and interns, and to reduce strain. Checklists are
      helpful on an "organisational level" (e.g., financial benefits, quality
      assurance) and to clarify responsibilities.

PMID- 24089242
TI  - Practical issues in the management of the long QT syndrome: focus on diagnosis
      and therapy.
AB  - The long QT syndrome (LQTS) is a leading cause of sudden death in the young. It
      is not as rare as previously assumed, given its established prevalence of 1:2,000
      live births. It is characterised by prolongation of the QT interval and by the
      occurrence of syncope, due to torsades-des-pointes ventricular tachycardia,
      cardiac arrest and sudden death; these life-threatening cardiac events are
      usually, but not always, associated with physical or emotional stress. It is a
      genetic disorder, and knowledge of the genotype impacts significantly on
      management. Extremely effective therapies are available, which makes the
      existence of undiagnosed affected and symptomatic patients inexcusable. Indeed,
      mortality for properly treated patients has now declined to around 1% over a 10
      year period. This review, aimed at the clinical cardiologist, discusses briefly
      the essential genetic information and focuses primarily on the main issues of
      diagnosis and therapy. One special point of interest is in the impact of genetics
      on clinical management and the potential medicolegal consequences of not pursuing
      genetic screening in the proband and hence in the family members. 

PMID- 24089243
TI  - Stable insulin-secreting ducts formed by reprogramming of cells in the liver
      using a three-gene cocktail and a PPAR agonist.
AB  - With the long-term aim of developing a new type of therapy for diabetes, we have
      investigated the reprogramming of liver cells in normal mice toward a pancreatic
      phenotype using the gene combination Pdx1, Ngn3, MafA. CD1 mice were rendered
      diabetic with streptozotocin and given a single dose of Ad-PNM, an adenoviral
      vector containing all three genes. Ad-PNM induced hepatocytes of the liver to
      produce insulin, and the blood glucose became normalized. But over several weeks,
      the insulin-positive cells were lost and the blood glucose rose back to diabetic
      levels. Simultaneous administration of a peroxisome-proliferator-activated
      receptor agonist, WY14643, caused remission of diabetes at a lower dose of Ad-PNM
      and also caused the appearance of a population of insulin-secreting ductal
      structures in the liver. The insulin-positive ducts were stable and were able to
      relieve diabetes in the long term. We show that the effect of WY14643 is
      associated with the promotion of cell division of the ductal cells, which may
      increase their susceptibility to being reprogrammed toward a beta cell fate. 

PMID- 24089246
TI  - Ribbon aromaticity in double-chain planar B(n)H2(2-) and Li2B(n)H2 nanoribbon
      clusters up to n = 22: lithiated boron dihydride analogues of polyenes.
AB  - We report an extensive density-functional theory and coupled-cluster CCSD(T)
      study on boron dihydride dianion clusters BnH2(2-) (n = 6-22) and their
      dilithiated Li2BnH2(0/-) salt complexes. Double-chain (DC) planar nanoribbon
      structures are confirmed as the global minima for the BnH2(2-) (n = 6-22)
      clusters. Charging proves to be an effective mechanism to stabilize and extend
      the DC planar nanostructures, capable of producing elongated boron nanoribbons
      with variable lengths between 4.3-17.0 A. For the dilithiated salts, the DC
      planar nanoribbons are lowest in energy up to Li2B14H2 and represent true minima
      for all Li2BnH2(0/-) (n = 6-22) species. These boron nanostructures may be viewed
      as molecular zippers, in which two atomically-thin molecular wires are zipped
      together via delocalized bonds. Bonding analysis reveals the nature of pi plus
      sigma double conjugation in the lithiated DC nanoribbon Li2BnH2(0/-) (n up to 22)
      model clusters, which exhibit a 4n pattern in adiabatic detachment energies,
      ionization potentials, and second-order differences in total energies. Band
      structure analysis of the infinite DC boron nanoribbon structure also reveals
      that both pi and sigma electrons participate in electric conduction, much
      different from the monolayer boron alpha-sheet in which only pi electrons act as
      carriers. A concept of "ribbon aromaticity" is proposed for this quasi-one
      dimensional system, where regular pi versus sigma alternation of the delocalized
      electron clouds along the nanoribbons results in enhanced stability for a series
      of "magic" nanoribbon clusters. The total number of delocalized pi and sigma
      electrons for ribbon aromaticity collectively conforms to the (4n + 2) Huckel
      rule. Ribbon aromaticity appears to be a general concept in other nanoribbon
      systems as well. 

PMID- 24089245
TI  - A journey in science: promise, purpose, privilege.
AB  - Real innovations in medicine and science are historic and singular; the stories
      behind each occurrence are precious. At Molecular Medicine we have established
      the Anthony Cerami Award in Translational Medicine to document and preserve these
      histories. The monographs recount the seminal events as told in the voice of the
      original investigators who provided the crucial early insight. These essays
      capture the essence of discovery, chronicling the birth of ideas that created new
      fields of research; and launched trajectories that persisted and ultimately
      influenced how disease is prevented, diagnosed, and treated. In this volume, the
      first Cerami Award Monograph, by Carl Nathan, MD, chairman of the Department of
      Microbiology and Immunology at Weill Cornell Medical College, reflects towering
      genius and soaring inspiration. 

PMID- 24089248
TI  - Microfluidic channels fabricated from poly(vinylmethylsiloxane) networks that
      resist swelling by organic solvents.
AB  - This paper describes the use of poly(vinylmethylsiloxane) (PVMS) networks for
      fabricating microfluidic channels that resist swelling in the presence of organic
      solvents, thus providing a versatile alternative to poly(dimethylsiloxane)
      (PDMS). In particular, we demonstrate that in contrast to PDMS microchannels, the
      UV-treated PVMS structures exhibit high resistance to swelling by toluene. 

PMID- 24089247
TI  - Influence of apolipoprotein A-I and apolipoprotein A-II availability on nascent
      HDL heterogeneity.
AB  - It is important to understand HDL heterogeneity because various subspecies
      possess different functionalities. To understand the origins of HDL heterogeneity
      arising from the existence of particles containing only apoA-I (LpA-I) and
      particles containing both apoA-I and apoA-II (LpA-I+A-II), we compared the
      abilities of both proteins to promote ABCA1-mediated efflux of cholesterol from
      HepG2 cells and form nascent HDL particles. When added separately, exogenous apoA
      I and apoA-II were equally effective in promoting cholesterol efflux, although
      the resultant LpA-I and LpA-II particles had different sizes. When apoA-I and
      apoA-II were mixed together at initial molar ratios ranging from 1:1 to 16:1 to
      generate nascent LpA-I+A-II HDL particles, the particle size distribution
      altered, and the two proteins were incorporated into the nascent HDL in
      proportion to their initial ratio. Both proteins formed nascent HDL particles
      with equal efficiency, and the relative amounts of apoA-I and apoA-II
      incorporation were driven by mass action. The ratio of lipid-free apoA-I and apoA
      II available at the surface of ABCA1-expressing cells is a major factor in
      determining the contents of these proteins in nascent HDL. Manipulation of this
      ratio provides a means of altering the relative distribution of LpA-I and LpA-I+A
      II HDL particles. 

PMID- 24089249
TI  - Catalytic enantioselective reductive desymmetrisation of achiral and meso
      compounds.
AB  - Herein an overview of reductive catalytic enantioselective desymmetrisation of
      achiral or meso compounds is provided. The most efficient reductive
      desymmetrisations described in the literature, which involve the reduction of
      C=O, C=N, C=C and C-halogen bonds, or reductive ring-opening, are summarised. The
      structural diversity of the valuable highly enantioenriched intermediates
      prepared by reductive desymmetrisation is highlighted.

PMID- 24089250
TI  - Swallowing pressure and pressure profiles in young healthy adults.
AB  - OBJECTIVES/HYPOTHESIS: To measure the swallowing pressure (SP) of normal subjects
      using a 2.64-mm-diameter high-resolution manometry (HRM) catheter with 36
      circumferential sensors. STUDY DESIGN: Repeated measures with subjects serving as
      controls. METHODS: Thirty healthy subjects swallowed water at different
      temperatures and volumes to examine the maximum SP at the velopharynx, meso
      hypopharynx, upper esophageal sphincter (UES), and cervical esophagus, and the
      duration of lowered pressure at the UES. RESULTS: The maximum SP at any location
      was unaffected by the volume of water, whereas the maximum SP at the UES and
      cervical esophagus was affected by the temperature. The duration of lowered SP at
      the UES was significantly prolonged with 10 versus 2 mL of cold water. The
      pressure curve in males had two peaks (at the velopharynx and UES), whereas that
      of females had a single peak at the UES. CONCLUSIONS: Our data obtained with 2.64
      mm HRM demonstrated that as the bolus volume is increased, the duration of
      lowered SP at the UES is prolonged. The higher maximum SP at the velopharynx in
      males versus females suggests that there may be a gender difference in pressure
      at the velopharynx that has not been described previously. This implies that it
      is necessary to take gender differences into consideration when evaluating the
      etiology of swallowing dysfunction by examining the SP and SP curve. Moreover,
      the thinner catheter is less invasive and may contribute to obtaining more
      physiological measurements.

PMID- 24089251
TI  - A facile copper(I)-catalyzed homocoupling of terminal alkynes to 1,3-diynes with
      diaziridinone under mild conditions.
AB  - A novel and efficient Cu(I)-catalyzed oxidative homocoupling of terminal alkynes
      with diaziridinone as an oxidant is described. Various terminal alkynes can be
      transformed into the corresponding 1,3-diynes in good yields. The reaction
      process is base-free, operationally simple, and amenable to the gram scale.

PMID- 24089252
TI  - Optimization and extraction of functional information from in vitro flow models
      using dual-beam spectral-domain optical coherence tomography cross-correlation
      analysis.
AB  - As in vivo flow behavior can be pulsatile, intermittent, and/or otherwise
      changeable with time, the ability to provide clinicians with a means of real-time
      visualization and functional assessment of structures is of particular
      importance. The discernment of pulsatile flow behavior using a dual-beam spectral
      domain optical coherence tomography system (db-SdOCT) by quasi-simultaneous
      measurement by two planes of illumination is demonstrated. By cross-correlation
      analysis, it is possible to compute velocity metrics pertaining to flowing
      particle motion, without a priori angular knowledge. This is the first
      application of cross-correlation-based dynamic assessment for the extraction of
      pulsatile behavior in an in vitro environment using an optimized db-SdOCT system.
      The experimental results outlined have shown the db-SdOCT system and its
      associated algorithms to be successful in the discernment of intermittent
      pulsatile flow behavior in in vitro models, concurrent to yielding velocity
      values in good agreement with that of the applied flow rate.

PMID- 24089253
TI  - Photoacoustic recovery after photothermal bleaching in living cells.
AB  - We present an innovative method, photoacoustic recovery after photothermal
      bleaching (PRAP), for studying particle dynamics at micron scale via
      photoacoustic imaging. As an intuitive way to visualize and quantify dynamic
      processes, PRAP is demonstrated first in a simple phantom study and then in a
      more complex measurement involving live cells. Compared with the conventional
      fluorescence-based approach, PRAP provides high signal-to-noise ratio (SNR)
      imaging with minimal bleaching-induced artifacts during the recovery stage, ideal
      for monitoring the diffusive and kinetic processes inside a cell.

PMID- 24089254
TI  - Cost-efficient speckle interferometry with plastic optical fiber for unobtrusive
      monitoring of human vital signs.
AB  - A cost-efficient plastic optical fiber (POF) system for unobtrusive monitoring of
      human vital signs is presented. The system is based on speckle interferometry. A
      laser diode is butt-coupled to the POF whose exit face projects speckle patterns
      onto a linear optical sensor array. Sequences of acquired speckle images are
      transformed into one-dimensional signals by using the phase-shifting method. The
      signals are analyzed by band-pass filtering and a Morlet-wavelet-based
      multiresolutional approach for the detection of cardiac and respiratory
      activities, respectively. The system is tested with 10 healthy nonhospitalized
      persons, lying supine on a mattress with the embedded POF. Experimental results
      are assessed statistically: precisions of 98.8% +/- 1.5% and 97.9% +/- 2.3%,
      sensitivities of 99.4% +/- 0.6% and 95.3% +/- 3%, and mean delays between
      interferometric detections and corresponding referential signals of 116.6 +/-
      55.5 and 1299.2 +/- 437.3 ms for the heartbeat and respiration are obtained,
      respectively.

PMID- 24089255
TI  - Optical parametric oscillator-based photoacoustic detection of hydrogen cyanide
      for biomedical applications.
AB  - A versatile, continuous wave, optical parametric oscillator is used in
      combination with photoacoustic spectroscopy for long-term trace gas experiments
      of volatile compounds emitted by biological samples. The optical parametric
      oscillator-based spectrometer (wavelength near 3 MUm, 8-MHz linewidth, output
      power ~1 W) is successfully tested for the detection of hydrogen cyanide (HCN)
      emission from clover leaves, and Pseudomonas bacteria; in addition, the presence
      of HCN in exhaled human breath is measured. For specific experiments, the
      spectrometer is operated continuously up to 10 days and has a detection limit of
      0.4 parts-per-billion volume of HCN in air over 10 s, using the P8 rotational
      line in the nu3 vibrational band of HCN at 3287.25 cm-1. This results in an
      overall sensitivity of the system of 2.5 * 10-9 cm-1 Hz-1/2.

PMID- 24089256
TI  - Spectral dependence of absorption sensitivity on concentration of oxygenated
      hemoglobin: pulse oximetry implications.
AB  - The sensitivity analysis indicates that the effective absorption coefficient is
      most sensitive to the concentration of oxygenated hemoglobin in spectral bands
      centered at 700 and 960 nm. We find that the highest temporal modulation due to
      heart function for a thick sample, like an arm, is at 940 nm, a significant shift
      from 710 nm measured for a finger. The most favorable spectral region for a thick
      transmission sample, such as a forearm, is the domain defined by intervals [900 
      nm <= lambda1 <= 1000  nm] and [650 nm <= lambda2 <= 720  nm]. We evaluated five
      near-infrared light-emitting diodes (LEDs) for their potential applications in
      oximetry. The LED with peak emission at 930 nm emits well in this spectral
      region. Here the temporal noise is low, and the effective absorption coefficient
      is strongly dependent on the concentration of the oxygenated hemoglobin. High
      quality saturation results are obtained through the forearm during a short
      measurement (30 s).

PMID- 24089257
TI  - The French Military influenza surveillance system (MISS): overview of
      epidemiological and virological results during four influenza seasons--2008-2012.
AB  - QUESTION UNDER STUDY: Influenza is a viral infection caused by a pathogen with
      considerable ability for genetic mutation, which is responsible for seasonal
      outbreaks as well as pandemics. This article presents the results of
      epidemiological and virological monitoring of four successive influenza outbreaks
      in the French armed forces, for the period 2008 to 2012. METHODS: The main events
      monitored were acute respiratory infection (ARI). Weekly incidence rates were
      calculated by relating cases to the number of servicepersons monitored. RESULTS:
      In continental France, the incidence rates for ARI and for medical consultation
      attributable to influenza were highest during the pandemic and decreased to reach
      their lowest values in 2010-2011 and 2011-2012. In terms of virological results,
      the 2008-2009 outbreak was mainly due to the A(H3N2) virus, while the 2009-2010
      pandemic and the following season saw the emergence of the A(H1N1) pdm09 strain.
      The last season 2011-2012 was characterised by a predominant circulation of
      A(H3N2) viruses. CONCLUSIONS: Despite some limitations, the MISS represents a
      good source of information about influenza in young people. Virological results
      are compatible with those reported by most other influenza surveillance networks,
      but could be improved by a better knowledge of the other respiratory viruses in
      circulation in the military community.

PMID- 24089258
TI  - In reference to Intratympanic dexamethasone injection for refractory tinnitus:
      prospective placebo-controlled study.

PMID- 24089259
TI  - Ambulatory blood pressure in chronic kidney disease: do ethnic disparities exist?

PMID- 24089260
TI  - Long-term compliance with salt restriction assessed using the spot urine method
      in Japanese cardiology outpatients.
AB  - The purpose of this study was to evaluate long-term compliance with salt
      restriction in Japanese cardiology outpatients assessed by spot urine
      measurements. A total of 466 patients (72 +/- 10 years old, 216 females) who
      visited a cardiology outpatient clinic and were followed for at least 1 year were
      included in this study. Daily dietary salt intake was estimated based on the
      sodium and creatinine concentrations determined by spot urine at the time of
      enrollment, during an 8-26 week follow-up and at a long-term follow-up (>1 year).
      The average follow-up duration was 2.2 +/- 0.6 (1.0-3.4) years after enrollment,
      and spot urines were collected 5.2 +/- 2.8 times after 1 year. The baseline
      estimated salt excretion was 9.6 +/- 2.7 g per day, which was reduced to 8.7 +/-
      2.3 g per day (P<0.01) at 8-26 weeks and remained unchanged at the long-term
      follow-up (8.9 +/- 2.0 g per day, P = 0.36 vs. 8-26 weeks, P < 0.01 vs.
      baseline). The percent of patients who achieved an average salt excretion<6.0 g
      per day was unchanged from baseline (6.9% vs. 7.7%, P = 0.61). Among several
      variables (gender, age, body weight, salt excretion at enrollment) that might
      affect the incidence of salt excretion <6.0 g per day, salt excretion at baseline
      was the only determinant of successful salt restriction (P<0.01). In conclusion,
      compliance with salt restriction, assessed using a spot urine method, was
      maintained over the long term; however, achieving salt reduction to the level
      recommended by the guidelines remains a challenge.

PMID- 24089261
TI  - The effect of sex on endothelial function responses to clamped hyperglycemia in
      type 1 diabetes.
AB  - Although the female sex is associated with renal protection in non-diabetic
      nephropathy, men and women with type 1 diabetes mellitus (T1D) have a similar
      risk of developing nephropathy. As hyperglycemia is associated with exaggerated
      effects on blood pressure and renal hyperfiltration in women versus men with T1D,
      we examined the influence of clamped hyperglycemia on flow mediated
      vasodilatation (FMD) to determine if this parameter contributes to sex-related
      differences in the vascular function. After a controlled diet for seven days,
      blood pressure, ultrasound derived FMD and circulating renin angiotensin system
      mediators were measured in men (n=30) and women (n=28) with T1D during clamped
      euglycemia and hyperglycemia. Men and women were similar in pre-study dietary
      parameters, age, diabetes duration, body mass index, HbA1c, renal function and
      proteinuria. The systolic blood pressure (SBP) was higher in men during clamped
      euglycemia (121+/-2 vs. 108+/-2 mm Hg, P<0.0001) and hyperglycemia (121+/-2 vs.
      111+/-2 mm Hg, P<0.0001), as were the circulating levels of angiotensin II
      (P<0.05). SBP increased in response to hyperglycemia in women but not in men.
      Consistently with differences in blood pressure during clamped euglycemia, FMD
      was higher in women than in men (8.06+/-0.55 vs. 4.15+/-0.52%, P<0.0001). In
      contrast, between-group differences in FMD during clamped hyperglycemia did not
      reach significance owing to a decline in FMD in women, versus men, in response to
      clamped hyperglycemia (P=0.040 for between-group change in FMD). Clamped
      hyperglycemia suppresses FMD in women, but not in men, with uncomplicated T1D,
      which may contribute to the relative loss of protection against renal disease
      progression in women with T1D. 

PMID- 24089262
TI  - Blood pressure control and management of very elderly patients with hypertension
      in primary care settings in Spain.
AB  - This study aimed to determine the clinical profile, blood pressure (BP) control
      rates, therapeutic management and physicians' therapeutic behavior regarding very
      elderly hypertensive patients. A total of 1540 hypertensive patients ?80 years
      old on antihypertensive therapy and receiving care in primary care settings in
      Spain were included in this cross-sectional study. The mean patient age was
      83.4+/-3.1 years, 61.9% of patients were women and 49.3% of patients had
      cardiovascular disease. Of the patients, 27.7% were on monotherapy and 72.3% were
      on combined therapy (47.4% on two antihypertensive agents and 24.9% on three or
      more antihypertensive agents). A total of 40.8% (95% confidence interval (CI):
      38.4-43.3%) of patients achieved BP goals (<140/90 mm Hg; <130/80 in patients
      with diabetes, chronic renal disease or cardiovascular disease). Patients with
      uncontrolled BP were more likely to have metabolic syndrome, diabetes, obesity, a
      history of cardiovascular disease, ischemic heart disease, renal disease and
      stroke and were more frequently smokers. Physicians modified the antihypertensive
      regimens for 27.4% (95% CI: 23.9-30.8%) of the patients with uncontrolled BP, and
      the addition of another antihypertensive agent was the most frequent
      modification. With regard to the physicians' perception of patients' BP control,
      the BPs of 44.1% of the patients with uncontrolled BP were considered well
      controlled by the physicians. 

PMID- 24089263
TI  - Blood pressure elevation in hemodialysis patients after the Great East Japan
      Earthquake.
AB  - A major earthquake measuring 9.0 on the Richter scale struck northeastern Japan
      at 2:46 pm on 11 March 2011. Several reports have described transient increases
      in blood pressure after major earthquakes, but the impact of such increases on
      hemodialysis patients has not been reported. We retrospectively investigated
      changes in blood pressure and influencing factors in 205 patients (mean age
      66.6+/-13.0 years; male 51.7%; median dialysis vintage 6.0 (2.0-11.0) years) on
      chronic dialysis at three dialysis centers in the affected area (Fukushima City)
      for 8 weeks after the earthquake. Pre-dialysis blood pressure was significantly
      elevated at 1 week after the earthquake compared with baseline (systolic vs.
      diastolic blood pressure: 153.1+/-20.2/80.1+/-13.5 vs. 148.6+/-20.0/77.5+/-12.8
      mm Hg, P<0.001), similarly post-dialysis blood pressure was elevated for up to 8
      weeks. Independent factors influencing changes in blood pressure after the
      earthquake comprised baseline blood pressure and alpha-blockers. The earthquake
      induced a significant elevation in blood pressure among patients on chronic
      dialysis, and activation of the sympathetic nervous system might at least in part
      be associated with the mechanism underlying this increase. 

PMID- 24089264
TI  - Telmisartan delays myocardial fibrosis in rats with hypertensive left ventricular
      hypertrophy by TGF-beta1/Smad signal pathway.
AB  - Hypertensive myocardial remodeling has an important role in the pathophysiology
      of hypertensive disease. This study suggests that telmisartan (TEL) can inhibit
      myocardial fibrosis of hypertensive left ventricular hypertrophy (LVH) through
      the transforming growth factor-beta1 (TGF-beta1)/Smad signaling pathway. Through
      echocardiography and hemodynamics, it was shown that TEL could improve cardiac
      function and reduce the degree of hypertensive LVH in hypertensive rats. Through
      immunoassay, it was shown that TEL could antagonize renin-angiotensin-aldosterone
      system expression in plasma and myocardial tissue. By Masson staining, Elisa and
      alkaline hydrolysis assays, it was demonstrated that TEL could significantly
      inhibit myocardial fibrosis in hypertensive rats and attenuate extracellular
      matrix-related proteins associated with pressure overload. Western blotting was
      used to detect the TGF-beta1/Smad signaling pathway protein expression of
      myocardial tissue, and it was further found that TEL could inhibit activation of
      the TGF-beta1/Smad signaling pathway. In conclusion, TEL could inhibit myocardial
      local angiotensin II (Ang II) level by directly affecting the Ang II receptor.
      TEL may also restore the balance of matrix metalloproteinases/tissue inhibitor of
      metalloproteinases, reduce myocardial collagen fibrosis and delay hypertensive
      LVH by affecting the TGF-beta1/Smad signaling pathway. 

PMID- 24089265
TI  - Sex differences in the association between serum uric acid levels and cardiac
      hypertrophy in patients with chronic kidney disease.
AB  - Several studies have documented an association between serum uric acid (SUA)
      concentration and cardiac hypertrophy in hypertensive patients; however, the
      association remains unclear in chronic kidney disease (CKD) patients. If there is
      an association between SUA and hypertrophy in these patients, it is unknown
      whether the association is different between men and women. Our aim in this study
      is to determine whether SUA is associated with cardiac hypertrophy in CKD
      patients, focusing on any sex differences. Two hundred sixteen CKD patients (117
      men and 99 women) were enrolled in this cross-sectional study. Patients
      prescribed uric acid-lowering agents and those with congestive heart failure,
      valvular heart disease, or ischemic heart disease were excluded from this study.
      Left ventricular mass index (LVMI) and left ventricular hypertrophy (LVH) were
      assessed using echocardiography. The prevalence of LVH was 58% in men and 47% in
      women. In multivariate linear regression analysis, SUA levels did not correlate
      with LVMI in men, whereas SUA was independently associated with LVMI in women
      (beta=0.27, P=0.02). Multivariate logistic regression analysis also revealed that
      diabetes mellitus (odds ratio (OR), 4.41; P=0.01) was associated with LVH in men,
      whereas age (OR, 1.13; P<0.01), hypertension (OR, 7.38; P=0.03) and SUA (OR,
      1.91; P=0.03) were associated with LVH in women. In female CKD patients, SUA
      levels were associated with LVMI and LVH, whereas there was no association in
      male patients. These observations suggest that an association between SUA levels
      and the development of cardiac hypertrophy is more likely in women than in men. 

PMID- 24089266
TI  - Genetic impact dominates over environmental effects in development of carotid
      artery stiffness: a twin study.
AB  - Arterial stiffness is an independent predictor of cardiovascular, cerebrovascular
      and all-cause mortality. Quantifying the genetic influence on the stiff arterial
      phenotype allows us to better predict the development of arterial stiffness. In
      this study, we aimed to determine the heritability of carotid artery stiffness in
      healthy twins. We studied 98 twin pairs of both sexes. We determined carotid
      artery stiffness locally using echo tracking and applanation tonometry. We
      estimated the heritability of stiffness parameters using structural equation
      modeling. The carotid distensibility coefficient showed the highest heritability
      (64%, 95% confidence interval 45-77%). The incremental elastic modulus,
      compliance and stiffness index beta also showed substantial heritability (62%,
      61% and 58%, respectively). The remaining 36-42% phenotypic variance was
      attributed to unshared environmental effects. Genetic influence appears to
      dominate over environmental factors in the development of carotid artery
      stiffness. Environmental factors may have an important role in favorably
      influencing the genetic predisposition for accelerated arterial stiffening. 

PMID- 24089268
TI  - [Results of bariatric surgery. Experience over 18 years].
AB  - BACKGROUND: Bariatric surgery is the gold-standard treatment for morbid obesity
      because it has low morbidity rates in high-volume centers and generates long term
      sustained weight loss. AIM: To describe our experience in bariatric surgery since
      the creation of our bariatric program in 1992. MATERIAL AND METHODS:
      Retrospective analysis of all patients subjected to bariatric surgery from 1992
      to December 2010. Data was obtained from the electronic institutional registry.
      The Procedures per-formed were open and laparoscopic Roux-en-Y gastric bypass
      (BPGA and BPGL, respectively), laparoscopic adjustable gastric band (BGAL) and
      laparoscopic sleeve gastrectomy (GML). RESULTS: A total of 4943 procedures were
      performed, 768 (16%) BPGA, 2558 (52%) BPGL, 199 (4%) BGAL and 1418 (29%) GML. The
      number of procedures progressively increased, from 100 cases in 2000 to over 700
      cases in 2008. Proportion of femoles and preoperative mean body mass Index
      fluctuated between 69 and 79% and 35 and 43 kg/m2, respectively, among the
      different procedures. Early and late complications fluctuated between Oto 1%
      (higher on BPGA) and 3 to 32.7% (higher on BGAL), respectively. The excess weight
      lost at five years was 76.1% in BPGA, 92.5% in BPGL and 53.7% in BGAL. The figure
      for GML at three years was 73.7%. CONCLUSIONS: The complication rates of this
      series of patients are similar to those reported in large series abroad. BPGL is
      still the most effective procedure; however GML is an attractive alternative for
      less obese patients.

PMID- 24089267
TI  - Inhibition of the Ca(2+)-sensing receptor rescues pulmonary hypertension in rats
      and mice.
AB  - A recent study from our group demonstrated that the Ca(2+)-sensing receptor
      (CaSR) was upregulated, and the extracellular Ca(2+)-induced increase in
      cytosolic Ca(2+) concentration ([Ca(2+)]cyt) was enhanced in pulmonary arterial
      smooth muscle cells from patients with idiopathic pulmonary arterial hypertension
      and animals with experimental pulmonary hypertension (PH). However, it is unclear
      whether CaSR antagonists (for example, NPS2143) rescue the development of
      experimental PH. We tested the rescue effects of NPS2143 in rats with
      monocrotaline (MCT)-induced PH and mice with chronic hypoxia-induced PH. For the
      NPS2143 treatment group, rats and mice were i.p. injected with NPS2143 once per
      day from days 14 to 24. Four weeks after MCT injection or exposure to normobaric
      hypoxia, the right ventricular (RV) systolic pressure, right heart hypertrophy
      (RV/LV+S ratio) and RV myocardial fibrosis were rescued or nearly restored to
      normal levels by NPS2143 treatment. The rescue effects of NPS2143 on experimental
      PH further support a critical role for the CaSR in the PH mechanism. Therefore,
      NPS2143 may be a promising potential treatment for pulmonary arterial
      hypertension. 

PMID- 24089269
TI  - [Mortality of acute pancreatitis in a 20 years period].
AB  - BACKGROUND: Mortality for acute pancreatitis (AP) in Chile has fluctuated between
      7 ana 10% in last years. AIM: To evaluate AP mortality over a period of 20 years
      in a clinical hospital in Santiago, Chile. MATERIAL AND METHODS: Review of the
      database of hospital discharges with the diagnosis of acute pancreatitis, between
      1990 and 2010 and the medical records of those patients. Age, gender, length of
      hospital stay, surgeries, percutaneous interventions and mortality were
      registered. To compare the evolution of the disease over time, patients were
      divided in two groups: those hospitalized between 1990 and 1999 and those
      hospitalized between 2000 and 2010. RESULTS: We reviewed the records of 1367
      patients with a median age of 48 years (48% men). In the first period, 93 of 637
      (14.6%) patients died, whereas in the second period, 22 of 730 patients died
      (3.0%). In the first and second period, 41.9 and 25.3% of patients were subjected
      to surgical procedures. The hospital stay was shorter in the second group,
      compared with the first (14.2 and 25.9 days respectively). CONCLUSIONS: There was
      a decrease in mortality caused by AP in the last 10 years, probably associated
      with a better interdisciplinary management of these patients.

PMID- 24089270
TI  - [Results of the explicit health guaranties program to correct anemia of end stage
      renal disease patients in dialysis].
AB  - BACKGROUND: In July 2010 end stage renal disease anemia correction was
      incorporated to the program of explicit health guaranties of the Ministry of
      Health. The treatment plan included intravenous iron and erythropoietin. The
      prescription of these medications carne from the deriving health organizations.
      AIM: To describe the results of that program in 11 dialysis facilities belonging
      to Fresenius Medical Care (a private organization) distributed in the six
      Metropolitan Health Services (MHS) in Santiago, Chile. MATERIAL AND METHODS: We
      selected 328 patients who remained in dialysis treatment at least between June
      2010 and March 2011 and had a packed red cell volume lower than 30%, representing
      the target of the Plan. The evolution of packed red cell volume and the
      proportion of anemic patients in the facilities from each MHS were evaluated.
      RESULTS: The two above mentioned variables began to improve only in December
      2010. In no MHS, with the exception of the Eastern MHS, the mean hematocrit
      improved to higher than 30%, nor was the proportion of anemic patients reduced to
      lower than 50%. CONCLUSIONS: Treatment of anemia of end stage renal disease in
      dialysis, implemented by the explicit health guaranties program of the Ministry
      of Health, was ineffective in almost all MHS in Santiago.

PMID- 24089271
TI  - [Levels of inflammatory cytokines and plasma cortisol in respiratory syncytial
      virus bronchiolitis].
AB  - BACKGROUND: An increased inflammatory innate response may play a role in
      pathogenesis of respiratory syncytial virus (RSV) infection. AIM: To quantify pro
      inflammatory cytokines (IL-6-IL-8, IL-2-P and TNF-a) in nasopharyngeal aspirate
      (NPA) and plasma, and plasma cortisol in previously healthy infants with RSV
      bronchiolitis. PATIENTS AND METHODS: We studied 49 infants aged less than one
      year of age with RSV bronchiolitis and 25 healthy controls. Severity was defined
      using a previously described modified score. We quantified interleukins in NPA
      and plasma by flow cytometry and plasma cortisol by radioimmunoanalysis. RESULTS:
      Among patients with RSV bronchiolitis, 25 were classified as severe and 24 as
      moderate or mild. Significantly higher levels of IL-6 and IL-8 in NPA and plasma
      and IL-lfi in NPA were found in children classified as severe, when compared to
      those with moderate or mild disease and controls. There was a positive
      correlation between IL-6 and cortisol in plasma (r = 0,55; p < 0,0001) and both
      were correlated with the severity of the disease. CONCLUSIONS: RSV bronchiolitis
      severity was associated with higher leveis of inflammatory interleukins and
      plasma cortisol.

PMID- 24089272
TI  - [Identification of educational needs among patients with HIV and their health
      care providers].
AB  - BACKGROUND: The success of educational interventions depends on the integration
      of educational programs into clinical practice. AIM: To determine the educational
      needs and perceived barriers of people living with HIV (PHIV) and their health
      care providers (HCP). MATERIAL AND METHODS: Qualitative study conducted in 60
      PHIV and 10 HCP. For data collection, a semi-structured in-depth interview was
      applied, addressing the educational needs (content, methodology, person, time,
      physical location) and identified barriers to implement an educational program
      for PHIV Content analysis technique was used for data analysis. RESULTS: PHIV and
      their HCP identified the same educational needs as the following: general-related
      content, psychological, sexual and secondary prevention aspects of the disease.
      Individual sessions with written material and web pages were identified as
      important resources to support education. Both PHIV and professionals expressed
      their willingness to participate in educational programs, but the most commonly
      identified barrier was lack of time. CONCLUSIONS: This study identifies the key
      elements to include in an educational program for Chilean PHIV from the user and
      professional perspective.

PMID- 24089273
TI  - [Prevalence of sudden death syndrome among children].
AB  - BACKGROUND: The sudden infant's death syndrome (SD) is the leading cause of death
      in children under one year. Despite advances in its study, the pathogenesis has
      not been yet fully elucidated. AIM: To assess the prevalence of SD in Chilean
      infants and its changes in recent years. MATERIAL AND METHODS: Review of birth
      and death databases of the Ministry of Health from 1997 to 2009. All cases
      diagnosed as SD, according to the lnternational Classification of Diseases, 10th
      edition, were selected. A demographic analysis was performed and mortality rates
      for each year were calculated. RESULTS: We identified 1442 cases of SD (847
      males, 517 deaths at home). The median age of death was 2 months (0 to 11.0
      months). Ninety six percent of deaths occurred in children aged <6 months.
      Mortality rate for SD was 0.45/1000 live births. There was a 23% reduction
      between 1997 and 2009. When analyzing geographic distribution, more cases were
      found in the Southern latitudes of the country. CONCLUSIONS: The overall rate of
      SD in Chile is higher than in European countries and in North America. The
      observed decrease in cases over the years is still far from optimal.

PMID- 24089274
TI  - [Association of the incidence of type 1 diabetes mellitus with environmental
      factors in Chile during the period 2000-2007].
AB  - BACKGROUND: Pollution and viral infections could be associated with the incidence
      of type 1 diabetes mellitus. AIM: To look for associations between the temporal
      patterns of Type 1 Diabetes Mellitus (T1D) in infants younger than the age of 15
      years, and environmental factors, such as air pollution and viruses. MATERIAL AND
      METHODS: Data registries from hospitals, emergency services, and the Infantile
      Diabetes Foundation were reviewed, corresponding to children aged less than 15
      years, who received their first insulin injection between 2000 and 2007. The
      incidence of type 1 diabetes was computed for each epidemiological week.
      Environmental ozone and particulate matter rates for each week were obtained from
      Environmental services. Rates of influenza and respiratory syncytial virus
      infections were obtained from the epidemiological department of the Ministry of
      Health. An ecological Bayesian Poisson regression model was fitted, introducing
      the covariates, lagged covariates and errors, to estimate the incidence by
      epidemiological week. RESULTS: Three factors were significant by the proposed
      model: particulate matter PPM 2.5 (relative risk (RR): 1.003) lagged by two
      weeks, influenza (RR: 0.1808) and RSV (RR: 1.021). Trends and seasonality were
      clearly controlled by these covariates, considering the epidemiological week as a
      counting period. CONCLUSIONS: These results show that environmental factors could
      be related to peaks of type 1 diabetes incidence.

PMID- 24089275
TI  - [An elevated neutrophil/lymphocyte ratio is associated with poor prognosis in
      stage II resected colon cancer].
AB  - BACKGROUND: The neutrophil/lymphocyte ratio is an effective marker of
      inflammation ana can have prognostic value in surgical patients. AIM: To evaluate
      the effect of an increased neutrophil/lymphocyte ratio (NLR) on perioperative
      complications ana overall ana disease-free survival in patients undergoing
      elective resection for stage II colon cancer. MATERIAL AND METHODS: Data was
      obtained from clinical charts, preoperative blood results and hospital records of
      all patients undergoing an elective curative resection for colon cancer, between
      2000 and 2007. Preoperative NLR was calculated. Follow-up was obtained from a
      prospectively maintained colorectal cancer database, clinical records and
      questionnaires. Uni and multivariable analysis were performed to identify
      associations, and survival analysis was performed using Kaplan-Meier curves.
      RESULTS: One hundred twenty two patients with a mean age of 69 years (52% males),
      were evaluated. Median follow-up was 73 months, and overall survival for 1 and 5
      years was 95% and 68%, respectively. On a multivariable analysis after adjusting
      for age, sex, tumor depth invasion, use of adjuvant therapies and American
      Society of Anesthesiology preoperative risk score, an NLR > 5 was associated with
      an increased perioperative complication rate (odds ratio: 3.06, p = 0.033).
      Kaplan-Meier survival analysis showed a worse overall and disease-free survival
      for patients with NLR greater than five. CONCLUSIONS: A preoperative NLR of five
      or more is associated with greater perioperative morbidity and worse oncological
      outcomes in patients undergoing resection for elective stage II colon cancer.

PMID- 24089276
TI  - [An update on amebiasis].
AB  - The description of Entamoeba dispar, and the recovery of Entamoeba moshkovskii
      from humans had a major impact in the epidemiology and clinical management of
      amebiasis. Infections range from asymptomatic colonization to hemorrhagic colitis
      and extra-intestinal diseases. Only a minority of amebiasis patients progress to
      the development of disease. Recent studies suggest that susceptibility to
      infection, and its outcome is influenced by the host, parasite genotype, and
      environment. The identification of Entamoeba histolytica is based on the
      detection of specific antigens by ELISA and DNA in stool and other clinical
      samples. Several diagnostic tests have been developed, including polymerase chain
      reaction, the technique of choice, for the detection and differentiation of E.
      histolytica, E. dispar, and E. moshkovskii. Combination of serologic tests with
      detection of the parasite DNA by PCR or antigen by ELISA offers the best approach
      to diagnosis. However, these techniques are impractical for clinical laboratories
      of developing countries. Clinicians must follow the guidelines of the World
      Health Organization to avoid unnecessary treatments. This review describes and
      discusses recent advances in amebiasis with emphasis in the clinical aspects and
      management of infection. 

PMID- 24089277
TI  - [Diagnosis and therapy of polyuric states in patients with acute cerebral
      injury].
AB  - In patients with acute cerebral injury, polyuric states can potentially trigger,
      maintain and aggravate the primary neurological damage, due to hypovolemia,
      arterial hypotension and alterations of osmolarity. The true incidence of the
      condition in this population is unknown. A widely validated definition of
      polyuric state is lacking and its etiology is multifactorial. There are two
      principal classes of polyuria: (a) aqueous polyuria with diabetes insipidus as
      the main cause; and (b) osmotic polyuria in which sodium, glucose or ureaplay the
      main role. Polyuric states are in close association with disorders of water and
      sodium metabolism and with alterations in acid-base balance. A detailed analysis
      of the history, clinical picture and simple laboratory determinations in blood
      and urine, are required for an adequate assessment of these polyuric states. The
      problem must be faced with pathophysiological reasoning and a systematic and
      sequential approach, because each disorder needs a specific therapy.

PMID- 24089278
TI  - [Recommendations for cancer prevention of World Cancer Research Fund (WCRF):
      situational analysis for Chile].
AB  - The main diet-related cancers include colorectal, lung, breast in
      (postmenopausal) women, stomach, esophagus, prostate and pancreas. After tobacco,
      obesity is the leading cause of cancer; it accounts for one third of all cancers.
      Cancer is associated with high total body fat, abdominal fat and weight gain in
      adult life. These are all potentially modifiable risk factors. Consumption of a
      "healthy diet" and living an "active life" can significantly reduce the risk of
      cancer. The aim of this study was to analyze the recommendations published by the
      World Cancer Research Fund (WCRF) and American Institute for Cancer Research
      (AICR) for the prevention of cancer in 2007. We compared the recommendations of
      Food, Nutrition and Physical Activity and the Prevention of Cancer: a global
      perspective", with the national situation in Chile, analyzing the national report
      on the prevalence of risk factors. Our main finding was that the pattern of
      consumption and lifestyles differ markedly from the WCRF recommendations: we
      observed an over consumption of sugary drinks and high intake of processed foods
      high in sodium and total fat and low consumption of legumes, vegetables, fruits
      high in antioxidants and fiber that protect from cancer. Chile has an increased
      cancer prevalence which is associated with poor quality diets, rising mean body
      mass index and a sedentary behavior. We recommend the strengthening programs to
      promote healthy diets and active living, in order to reduce cancer risk. 

PMID- 24089279
TI  - [Osteoarticular paleopathology in a Chinchorro body: report of one case].
AB  - We report a severe osteo-arthropathy in a body of a Chinchorro adult mole exhumed
      from the pre-Hispanic site of Playa Miller 8, located in the city of Arica, on
      the northern coast of Chile. The advanced state of joint disease shows that the
      individual was cared by his social group, to be able to survive. This care was
      perpetuated in the postmortem treatment, applying red color to the body.
      Particular self-care social dynamics of Chinchorro society are inferred.

PMID- 24089280
TI  - [Proposing a data mining scaffolding for preventing harmful alcohol consumption
      in Chilean adolescents].
AB  - BACKGROUND: Adolescent alcohol and drug consumption are important public health
      problems in the Chilean young population. AIM: The purpose of this study was to
      examine the potential ofa data mining approach in scaffolding policy making,
      using the particular case of differential risks of harmful alcohol consumption in
      adolescent students. MATERIAL AND METHODS: Index and control groups were composed
      by 7918 and 7138 participants respectively (drawn from a CONACE survey 2009),
      aged 16 +/- 2 years, 52% mole. Heavy drinking at last month was the independent
      variable. As dependent variables parenting style, peer group influence, age and
      sex were used. For data analysis, a data mining approach was applied (CART, SPSS
      version 15). RESULTS: The peer group influence was the main discriminant variable
      in males and the total sample, proving to be the only relevant variable in the
      case of women. The results suggest how a data mining approach may be useful in
      order to develop a hard data scaffolding for making and implementing policies in
      general and policies addressing adolescent alcohol consumption in particular.

PMID- 24089281
TI  - [Certification of internal medicine specialists in Chile by the autonomous
      corporation for certification of medical specialties].
AB  - Since 1984, 12.294 different medical specialists have been certified in Chile by
      the Autonomous Corporation for Certification of Medical Specialties (whose
      Spanish acronym is CONACEM). Infernal Medicine certification started in 1985,
      approving 1364 candidates thus far. Certification can be obtained in three ways.
      Sixty one percent of applicants were approved by a reputable university
      specialization program. Thirty five percent of applicants fulfilled the
      requirements of a five years practical training program and less than 5% were
      approved in a training program from another country which was validated in Chile.
      There are 13 university training programs for medical specialties, lasting three
      years each. These programs can receive a total of 110 students per year. Half of
      these programs are not carried out in Santiago. Applicants, who have not
      completed a certified university training program, must go through a five days
      practical examination. Since 2002 a written test was added, whose approval is a
      requisite to gain access to the practical examination. Sixty one percent of
      applicants have approved the theoretical test. Certifications last 10 years
      initially and seven years, there after. When certifications expire, a
      recertification mechanism is required, whose requirements are informed. According
      to the current legislation, certifications must be done by recognized accrediting
      agencies. CONACEM has been accepted by the authority and its definitive legal
      recognition should be a reality soon. 

PMID- 24089282
TI  - [Histiocytic necrotizing lymphadenitis: report of 3 cases].
AB  - Histiocytic necrotizing lymphadenitis (also known as Kikuchi-Fujimoto's disease)
      is an uncommon, benign and self-limiting lymph disease. We report three patients
      aged 14, 22 and 50 years, who presented with fever and cervical lymphadenopathy,
      accompanied by skin lesions and joint pain in two of the three cases. One of the
      patient's sister suffered from histiocytic necrotizing lymphadenitis. Laboratory
      abnormalities varied and findings included leucopenia, relative neutrophilia,
      elevated C reactive protein, erythrocyte sedimentation rate and ferritin. Basic
      laboratory screening tests were performed on all patients to rule out autoimmune
      and infectious diseases. Lymph node biopsy and subsequent pathological
      examination were essential to establish the diagnosis. All patients received
      antibiotics at some point of their hospital stay. Two patients required
      glucocorticoid treatment, while the remaining case experienced a spontaneous
      recovery. Its pathogenesis is still unknown, but clinical and histopathological
      studies suggest a connection with autoimmune diseases. There is no established
      treatment, but apparently the disease responds to the administration of
      glucocorticoids. 

PMID- 24089283
TI  - [Radiation organizing pneumonia: report of one case].
AB  - We report a 64-years-old woman who underwent sparing mastectomy with adjuvant
      radiotherapy for breast cancer. One month after the end of radiotherapy, she
      presented with malaise, fever, fatigue, cough and migratory bilateral pulmonary
      infiltrates on serial radiological images. The microbiological studies of broncha
      alveolar lavage were negative. The patient under went a trans bronchial biopsy
      and the pathological diagnosis was compatible with an organizing pneumonia
      presumably associated with radiotherapy. Systemic steroid treatment was
      successful with rapid and complete resolution of clinical and radiographic
      manifestations.

PMID- 24089284
TI  - [In vitro cell response to chemotherapeutic agents, to personalize ovarian cancer
      treatment: report of two cases].
AB  - Our laboratory has implemented an in vitro assay to estimate the response to
      chemotherapy in ovarian cancer cells pertaining to individual patients. In two
      selected patients, we determined the correlation between an in vitro assay of
      cells from suspected ovarian cancer ascites, with the clinical chemotherapy
      response. Cancer cells isolated from peritoneal fluid with suspected ovarian
      cancer were tested for cytotoxicity with corresponding chemotherapy regimens.
      Circulating Cal25 levels and attending physician consultation determined clinical
      course and response to chemotherapy. The in vitro assay result correlated with
      Cal25 levels, progression free survival and attending physician evaluation. The
      assay predicted correctly the failure of two successive chemotherapy regimes in
      the first patient, while predicting a favorable clinical response in the second
      subject. 

PMID- 24089285
TI  - [Reflections on medical conferences and meetings].

PMID- 24089286
TI  - [Reflections on medical conferences and meetings: a reply from the editor].

PMID- 24089287
TI  - [Tonegawa syndrome].

PMID- 24089288
TI  - [Early detection of bowel cancer in occupational surveillance examinations:
      switching from a guaiak-based to an immunochemical fecal occult blood test].
AB  - BACKGROUND: If the diagnosis is made early the cure rate of bowel cancer is more
      than 90 %. Occupational preventative medical care required by law and carried out
      by company physicians can be supplemented by a medical consultation and by simple
      screenings to interest employees in cancer prevention and refer them to
      registered general practitioners and specialist doctors for further diagnosis and
      treatment. SUBJECTS AND METHODS: Since 2001, BASF SE in Ludwigshafen, Germany
      offers its employees aged 45 and more a program to detect intestinal cancer
      early. The employees receive personal invitations for this program once a year.
      The participants answer a standard questionnaire about risk factors for bowel
      cancer and an endoscopic diagnosis, if this has already been carried out, and
      receive a FOBT. Since 2010 an immunological test system was used. We compare the
      results from two consecutive years with a Guajacum test system (g-FOBT) and an
      immunological test (i-FOBT). The German Association of Digestive and Metabolic
      Diseases, DGVS, recommends a colonoscopy if test results are positive or a family
      member has suffered from bowel cancer. RESULTS: Between 2008 and 2011, a total of
      52,797 invitations were sent to employees aged 45 and over. Overall, 16,730 men
      (37.7 % of 46,245) and 1,585 women (24.4 % of 6,552) took part (in some cases
      more than once). The return rate of the FOBT increased from 66.7 % in 2008 to
      79.5 % in 2011. Due to positive results and/or suspicious information in the
      questionnaire, 2,441 colonoscopies were recommended, 849 of them because of a
      positive FOBT. The medical department was informed of 224 endoscopy diagnoses. In
      8 cases, manifested cancer (6 * colon, 2 * rectum) and in 57 cases adenomatous
      polyps were diagnosed as preliminary stages of cancer. Most of these diagnoses
      were made using the i-FOBT, the simultaneous increase in positive test results
      and therefore more frequent recommendations for a colonoscopy. CONCLUSION: The
      additional offer of a program for early detection of bowel cancer as part of an
      occupational surveillance examination helps detecting bowel cancer early in
      employees who show no symptoms. Since men on average fall ill earlier, it makes
      sense to offer these tests at the age of 45.  Personal invitations lead to
      consistently high participant rates and the simplicity of the i-FOBT leads to
      high return rates of tests. The rate of positive test results is higher compared
      to g-FOBT. In our follow-up, significantly more intestinal cancer and possible
      preliminary stages were detected through screening with the immunological test.

PMID- 24089289
TI  - Solid-phase single molecule biosensing using dual-color colocalization of
      fluorescent quantum dot nanoprobes.
AB  - The development of solid-phase surface-based single molecule imaging technology
      has attracted significant interest during the past decades. Here we demonstrate a
      sandwich hybridization method for highly sensitive detection of a single thrombin
      protein at a solid-phase surface based on the use of dual-color colocalization of
      fluorescent quantum dot (QD) nanoprobes. Green QD560-modified thrombin binding
      aptamer I (QD560-TBA I) were deposited on a positive poly(l-lysine) assembled
      layer, followed by bovine serum albumin blocking. It allowed the thrombin protein
      to mediate the binding of the easily detectable red QD650-modified thrombin
      binding aptamer II (QD650-TBA II) to the QD560-TBA I substrate. Thus, the
      presence of the target thrombin can be determined based on fluorescent
      colocalization measurements of the nanoassemblies, without target amplification
      or probe separation. The detection limit of this assay reached 0.8 pM. This
      fluorescent colocalization assay has enabled single molecule recognition in a
      separation-free detection format, and can serve as a sensitive biosensing
      platform that greatly suppresses the nonspecific adsorption false-positive
      signal. This method can be extended to other areas such as multiplexed
      immunoassay, single cell analysis, and real time biomolecule interaction studies.

PMID- 24089290
TI  - The Warwick Hip Trauma Evaluation One -an abridged protocol for the WHiTE One
      Study: An embedded randomised trial comparing the X-bolt with slidinghip screw
      fixation in extracapsular hip fractures.
AB  - Fractures of the proximal femur are one of the greatest challenges facing the
      medical community, constituting a heavy socioeconomic burden worldwide.
      Controversy exists regarding the optimal treatment for patients with unstable
      trochanteric proximal femoral fractures. The recognised treatment alternatives
      are extramedullary fixation usually with a sliding hip screw and intramedullary
      fixation with a cephalomedullary nail. Current evidence suggests that best
      results and lowest complication rates occur using a sliding hip screw.
      Complications in these difficult fractures are relatively common regardless of
      type of treatment. We believe that a novel device, the X-Bolt dynamic plating
      system, may offer superior fixation over a sliding hip screw with lower
      reoperation risk and better function. We therefore propose to investigate the
      clinical effectiveness of the X-bolt dynamic plating system compared with
      standard sliding hip screw fixation within the framework of a the larger WHiTE
      (Warwick Hip Trauma Evaluation) Comprehensive Cohort Study. Cite this article:
      Bone Joint Res 2013;2:206-9. 

PMID- 24089291
TI  - The Warwick Hip Trauma Evaluation Two -an abridged protocol for the WHiTE Two
      Study: An embedded randomised trial comparing the Dual-Mobility withpolyethylene
      cups in hip arthroplasty for fracture.
AB  - Fractures of the proximal femur are one of the greatest challenges facing the
      medical community, constituting a heavy socioeconomic burden worldwide.
      Controversy exists regarding the optimal treatment for independent patients with
      displaced intracapsular fractures of the proximal femur. The recognised
      alternatives are hemiarthroplasty and total hip replacement. At present there is
      no established standard of care, with both types of arthroplasty being used in
      many centres. The principal advantages of total hip replacement are a functional
      benefit over hemiarthroplasty and a reduced risk of revision surgery. The
      principal criticism is the increased risk of dislocation. We believe that an
      alternative acetabular component may reduce the risk of dislocation but still
      provide the functional benefit of total hip replacement in these patients. We
      therefore propose to investigate the dislocation risk of a dual-mobility
      acetabular component compared with standard polyethylene component in total hip
      replacement for independent patients with displaced intracapsular fractures of
      the proximal femur within the framework of the larger WHiTE (Warwick Hip Trauma
      Evaluation) Comprehensive Cohort Study. Cite this article: Bone Joint Res
      2013;2:210-13. 

PMID- 24089292
TI  - Dynamic optical coherence tomography measurements of elastic wave propagation in
      tissue-mimicking phantoms and mouse cornea in vivo.
AB  - We demonstrate the use of phase-stabilized swept-source optical coherence
      tomography to assess the propagation of low-amplitude (micron-level) waves
      induced by a focused air-pulse system in tissue-mimicking phantoms, a contact
      lens, a silicone eye model, and the mouse cornea in vivo. The results show that
      the wave velocity can be quantified from the analysis of wave propagation,
      thereby enabling the estimation of the sample elasticity using the model of
      surface wave propagation for the tissue-mimicking phantoms. This noninvasive,
      noncontact measurement technique involves low-force methods of tissue excitation
      that can be potentially used to assess the biomechanical properties of ocular and
      other delicate tissues in vivo.

PMID- 24089293
TI  - Anti-vascular endothelial growth factor for neovascular glaucoma.
AB  - BACKGROUND: Neovascular glaucoma (NVG) is a potentially blinding secondary
      glaucoma. It is caused by the formation of abnormal new blood vessels which
      prevent normal drainage of aqueous from the anterior segment of the eye. Anti
      vascular endothelial growth factor (anti-VEGF) agents are specific inhibitors of
      the primary mediators of neovascularization. Studies have reported the
      effectiveness of anti-VEGFs for the control of intraocular pressure (IOP) in NVG.
      OBJECTIVES: To compare the IOP lowering effects of intraocular anti-VEGF agents
      to no anti-VEGF treatment, as an adjunct to existing modalities for the treatment
      of NVG. SEARCH METHODS: We searched CENTRAL (which contains the Cochrane Eyes and
      Vision Group Trials Register) (The Cochrane Library 2012, Issue 12), Ovid
      MEDLINE, Ovid MEDLINE In-Process and Other Non-Indexed Citations, Ovid MEDLINE
      Daily, Ovid OLDMEDLINE, (January 1950 to January 2013), EMBASE (January 1980 to
      January 2013), Latin American and Caribbean Literature on Health Sciences
      (LILACS) (January 1982 to January 2013), the metaRegister of Controlled Trials
      (mRCT) (www.controlled-trials.com), ClinicalTrials.gov (www.clinicaltrials.gov/)
      and the WHO International Clinical Trials Registry Platform (ICTRP)
      (www.who.int/ictrp/search/en). We did not use any date or language restrictions
      in the electronic searches for trials. We last searched the electronic databases
      on 11 January 2013. SELECTION CRITERIA: We included randomized controlled trials
      (RCTs) and quasi-RCTs of people treated with anti-VEGF agents for NVG. DATA
      COLLECTION AND ANALYSIS: Two authors independently assessed the search results
      for trials to be included in the review. Discrepancies were resolved by
      discussion with a third author. Since no trial met our inclusion criteria, no
      assessment of risk of bias or meta-analysis was undertaken. MAIN RESULTS: No RCTs
      were found that met the inclusion criteria for this review. Two RCTs of anti-VEGF
      agents for treating NVG were not included in the review due to the heterogeneity
      and uncontrolled assignment of adjunct treatments received by the study
      participants. AUTHORS' CONCLUSIONS: Currently available evidence is insufficient
      to evaluate the effectiveness of anti-VEGF treatments, such as intravitreal
      ranibizumab or bevacizumab, as an adjunct to conventional treatment in lowering
      IOP in NVG. Well designed RCTs are needed to address this issue, particularly
      trials that evaluate long-term (at least six months) benefits and risks since the
      effects of anti-VEGF agents may be short-term only. An RCT comparing anti-VEGF
      agents with no anti-VEGF agents taking into account the need for co
      interventions, such as panretinal photocoagulation (PRP), glaucoma shunt
      procedures, cyclodestructive procedures, cataract surgery, and deep vitrectomy,
      could be of use to investigate the additional beneficial effect of anti-VEGF
      agents in treating NVG. Since decisions for when and which co-interventions
      should be used are based on clinical criteria, they would not be appropriate for
      randomization. However, the design of a study on this topic should aim to balance
      groups by stratification of co-intervention at time of randomization or by
      enrolling a sufficient number of participants to conduct subgroup analysis by co
      interventions (ideally 15 participants per treatment group for each subgroup).
      Alternatively, the inclusion criteria for a trial could limit participants to
      those who receive the same co-intervention.

PMID- 24089294
TI  - Cost-effectiveness of ticagrelor and generic clopidogrel in patients with acute
      coronary syndrome in Switzerland.
AB  - QUESTION UNDER STUDY: The aim of this study was to evaluate the cost
      effectiveness of ticagrelor and generic clopidogrel as add-on therapy to
      acetylsalicylic acid (ASA) in patients with acute coronary syndrome (ACS), from a
      Swiss perspective. METHODS: Based on the PLATelet inhibition and patient Outcomes
      (PLATO) trial, one-year mean healthcare costs per patient treated with ticagrelor
      or generic clopidogrel were analysed from a payer perspective in 2011. A two-part
      decision-analytic model estimated treatment costs, quality-adjusted life years
      (QALYs), life years and the cost-effectiveness of ticagrelor and generic
      clopidogrel in patients with ACS up to a lifetime at a discount of 2.5% per
      annum. Sensitivity analyses were performed. RESULTS: Over a patient's lifetime,
      treatment with ticagrelor generates an additional 0.1694 QALYs and 0.1999 life
      years at a cost of CHF 260 compared with generic clopidogrel. This results in an
      Incremental Cost Effectiveness Ratio (ICER) of CHF 1,536 per QALY and CHF 1,301
      per life year gained. Ticagrelor dominated generic clopidogrel over the five-year
      and one-year periods with treatment generating cost savings of CHF 224 and 372
      while gaining 0.0461 and 0.0051 QALYs and moreover 0.0517 and 0.0062 life years,
      respectively. Univariate sensitivity analyses confirmed the dominant position of
      ticagrelor in the first five years and probabilistic sensitivity analyses showed
      a high probability of cost-effectiveness over a lifetime. CONCLUSION: During the
      first five years after ACS, treatment with ticagrelor dominates generic
      clopidogrel in Switzerland. Over a patient's lifetime, ticagrelor is highly cost
      effective compared with generic clopidogrel, proven by ICERs significantly below
      commonly accepted willingness-to-pay thresholds.

PMID- 24089295
TI  - Pulmonary complications in chronic liver disease.
AB  - The association of chronic liver disease with respiratory symptoms and hypoxia is
      well recognized. Over the last century, three pulmonary complications specific to
      chronic liver disease have been characterized: hepatopulmonary syndrome (HPS),
      portopulmonary hypertension (POPH), and hepatic hydrothorax (HH). The development
      of portal hypertension is fundamental in the pathogenesis of each of these
      disorders. HPS is the most common condition, found in 5%-30% of cirrhosis
      patients, manifested by abnormal oxygenation due to the development of
      intrapulmonary vascular dilatations. The presence of HPS increases mortality and
      impairs quality of life, but is reversible with liver transplantation (LT). POPH
      is characterized by development of pulmonary arterial hypertension in the setting
      of portal hypertension, and is present in 5%-10% of cirrhosis patients evaluated
      for LT. Screening for POPH in cirrhosis patients eligible for LT is critical
      since severe POPH is a relative contraindication for LT. Patients with moderate
      POPH, who respond adequately to medical therapy, may benefit from LT, although
      sufficient controlled data are lacking. HH is a transudative pleural effusion
      seen in 5%-10% of cirrhosis patients, in the absence of cardiopulmonary disease.
      Diagnosis of HH should prompt consideration for LT, which is the ultimate
      treatment for HH. Conservative management includes salt restriction and
      diuretics, with thoracentesis and transjugular intrahepatic portosystemic shunt
      (TIPS) as second-line therapeutic options.

PMID- 24089297
TI  - Common variants of the EPDR1 gene and the risk of Dupuytren's disease.
AB  - The object of this study was the investigation of 3 common variants of single
      nucleotide polymorphisms of the ependymin-related gene 1 and its association with
      the occurrence of Dupuytren's disease. DNA samples were obtained from the
      peripheral blood of 508 consecutive patients. The control group comprised 515
      healthy adults who were age-matched with the Dupuytren's patients. 3 common
      variants were analysed using TaqMan(r) genotyping assays and sequencing. The
      differences in the frequencies of variants of single nucleotide polymorphisms in
      patients and the control group were statistically tested. Additionally, haplotype
      frequency and linkage disequilibrium were analysed for these variants. A
      statistically significant association was noted between rs16879765_CT,
      rs16879765_TT and rs13240429_AA variants and Dupuytren's disease. 2 haplotypes:
      rs2722280_C+rs13240429_A+rs16879765_C and rs2722280_C+rs13240429_G+rs16879765_T
      were found to be statistically significantly associated with Dupuytren's disease.
      Moreover, we found that rs13240429 and rs16879765 variants were in strong linkage
      disequilibrium, while rs2722280 was only in moderate linkage disequilibrium. No
      significant differences were found in the frequencies of the variants of the gene
      between the groups with a positive and negative familial history of Dupuytren's
      disease. In conclusion, results of this study suggest that EPDR1 gene can be
      added to a growing list of genes associated with Dupuytren's disease development.

PMID- 24089296
TI  - Right iliac fossa pain.

PMID- 24089298
TI  - [Dupuytren's disease - patient satisfaction and functional results one year after
      partial fasciectomy and injection of collagenase].
AB  - INTRODUCTION: The gold standard in the treatment of Dupuytren's disease is the
      partial fasciectomy (PF). Injection of a collagenase directly into the Dupuytren
      cord is an alternative method. In contrast to needle fasciotomy, destruction of
      the cord is achieved enzymatically and not mechanically. 24 h after injection,
      the treated finger can be extended passively to disrupt the Dupuytren cord.
      PATIENTS AND METHODS: Functional outcome and patient satisfaction were
      prospectively analysed in 2 comparable groups of patients with the same stage of
      disease. Follow-up was one year. Patients in the first group underwent partial
      fasciectomy (PF) (n=13), whereas patients in the second group were treated by an
      injection of collagenase (CG) in the diseased tissue (n=14). Besides clinical
      examination, outcome was evaluated by validated questionnaires (DASH/MHQ) and a
      customised questionnaire. RESULTS: Extension after PF (mean residual contracture
      7.5 degrees ) was better than after collagenase injection (mean residual
      contracture 13.2 degrees ). Side-effects like numbness, impaired blood
      circulation and pain were less after injection of collagenase than after PF and
      of shorter duration. Recovery of grip strength was faster in the CG than after PF
      and collagenase injection was regarded as less discomforting. The results of the
      questionnaires showed a reduction of hand function 1 month after surgery, whereas
      better results were observed 1 month after collagenase injection. Recovery in the
      CG was significantly faster than after PF. DISCUSSION: Collagenase injection, as
      a less invasive technique, has less and milder side-effects than surgery and
      demonstrated a better total reduction of Dupuytren's contracture initially,
      although the residual contractures were higher in the CG after follow-up of 1
      year. Patient satisfaction was higher after collagenase injection due to
      subjectively perceived less negative impact and a comparable functional outcome.

PMID- 24089299
TI  - [Return of sensitivity after digital nerve reconstruction in children: how does
      age affect outcome?].
AB  - BACKGROUND: The regenerative capacity after nerve reconstruction in children is
      believed to be superior compared to that in adults. However, the available data
      on this topic are limited. The aim of this work is to improve the age-dependent
      assessment of the prognosis after surgical treatment of peripheral nerve injuries
      of the hand. PATIENTS AND METHODS: 44 of 147 children with complete transections
      of proper and common digital nerves who were treated from 2000 to 2009 and who
      were currently 6 years or older, could be included for follow-up (mean time, 7.5
      years). In total there were 60 nerve injuries, of which 56 were directly
      coaptated, 4 needed grafting. Sensitivity of the fingertips was assessed using
      the 2-point discrimination (2PD) test and the Semmes-Weinstein monofilament test.
      We also recorded hypersensitivity, sensitivity to cold, and paresthesia. To
      account for inter-individual differences in normal 2PD, the difference of the 2PD
      to the uninjured contralateral side was calculated as delta-2PD. The age at the
      time of the injury, divided into groups of 0-5, 6-10 and 11-15 years was
      correlated with the clinical outcome (2PD, monofilamenttest). Taking into account
      the results classified by age presented by Lohmeyer et al. and Mailander et al.,
      we assessed the correlation between age at injury (0-85 years) and clinical
      outcome. RESULTS: After 52 of the 56 direct nerve coaptations (93%) normal
      sensitivity was found with a 2PD<6 mm, 4 times the 2PD was 6 mm. Following nerve
      grafting a static 2PD of 6-7 mm was measured. Disturbing paresthesia, sensitivity
      to cold or hypersensitivity were not reported by any patient. The 2PD of the
      fingers of the opposite uninjured side showed great inter-individual differences.
      Patient's age and 2PD significantly correlated with significantly poorer results
      already in the second decade of life. CONCLUSION: In relation to adults, children
      have an excellent prognosis after nerve reconstruction. The high inter-individual
      differences in regular sensitivity, depending on age, co-morbi-dities, etc.,
      suggest putting the results of the injured and uninjured sides into relation.
      Estimation of the Deltas2PD may solve this -problem.

PMID- 24089300
TI  - [The "wide-awake approach" - efficiency and patient safety in carpal tunnel
      releases].
AB  - In order to improve operating room efficiency in our institution, we introduced
      the wide-wake approach for carpal tunnel releases in 2012. This study examines
      the effect of this new anaesthetic technique on the work-flow and the duration of
      operation compared to the previously used axillary plexus anaesthesia.In this
      retrospective study, we reviewed the surgical case data of all patients in whom
      carpal tunnel releases had been performed as single procedures. 120 procedures of
      the year 2011, performed under axillary plexus anaesthesia, were compared to 153
      procedures of the year 2012, performed as wide-awake surgery. We hypothesised
      that an earlier beginning of the first operation of the day with wide-awake
      surgery. Furthermore, we expected a shorter surgical time as well as a shorter
      interval between 2 carpal tunnel releases.By introduction of the wide-awake 
      approach, the first operation began a mean of 11 min earlier (p<0.001). While the
      surgical time did not change for the hand surgeon himself (10.7 vs. 10.2 min;
      p=0.478), the surgical time shortened significantly, when residents performed the
      operation (19.1 vs. 15.9 min, p<0.001). The interval between 2 carpal tunnel
      releases shortened from 19.8 to 17.7 min (p=0.009). Secure preparation was
      accomplished by the hypoperfused situs, when the wide-awake approach was applied,
      even though a tourniquet was not used. In the post-operative control, no
      complicated wound healings were noted.The wide-awake approach has proven to be
      reliable for the operating room -efficiency and, likewise, for patient safety.
      Therefore, we can recommend this technique without restrictions for carpal tunnel
      releases. 

PMID- 24089301
TI  - [Commentary on "the "wide-awake approach" - efficiency and patient safety in
      carpal tunnel releases" by S. Low, D. Herold and C. Eingartner].

PMID- 24089302
TI  - [Effect of wrist arthroscopy with intraarticular hyaluronan substitution therapy:
      a randomised, controlled, prospective, non-blinded, single-centre, comparative
      trial].
AB  - PURPOSE: The present study investigates the effect of an intra- and postoperative
      intraarticular hyaluronan injection (HS) in patients undergoing wrist
      arthroscopy. PATIENTS AND METHODS: A total of 140 adults were included and
      prospectively randomised to one of 2 treatment groups. All patients presented
      wrist pain resistant to non-operative therapy. 69 patients were assigned to
      therapeutic wrist arthroscopy without additional treatment (A-group), another 70
      patients were assigned to wrist arthroscopy and additional intraarticular
      instillation of a 1% HS solution (HS-group). The HS administration (2 mL of 1% HS
      solution each) was performed directly at the end of arthroscopic procedure and a
      second time 3 weeks after surgery. For outcome assessment, Mayo wrist score
      (modified according to Krimmer, MMWS), DASH questionnaire, absolute grip
      strength, VAS pain (visual analogue scale) and clinical global impression (CGI)
      of patients and investigators were used. The follow-up was 6 months. Furthermore,
      the correlation between severity of pathological findings and level of
      postoperative benefit was investigated. RESULTS: In both groups, pain decreased
      and the function of the wrist joint improved. While pa-tients with additional HS
      injection had significantly better values in MMWS than patients without
      additional HS injection, no significant differences could be observed for DASH
      score, absolute grip strength and pain intensity. 12 and 24 weeks after surgery,
      therapeutic success was rated better in HS-group than in A-group. The highest
      clinical benefit was obtained for patients in the HS-group with marginal to
      moderate pathological findings. CONCLUSION: The benefit of therapeutic wrist
      arthroscopy can be significantly improved by a 2-time intraarticular substitution
      of hyaluronan.

PMID- 24089303
TI  - [Commentary on "effect of wrist arthroscopy with intraarticular hyaluronan
      substitution therapy: a randomised, controlled, prospective, non-blinded, single
      centre, comparative trail" by a. Schutz and p. Dobner].

PMID- 24089304
TI  - [The hidradenocarcinoma of the wrist - an extremely rare malignant carcinoma:
      case presentation and literature review].
AB  - Hidradenocarcinomas are rare, yet highly malignant tumors of eccrine sweat gland
      origin. Due to its locally aggressive growth and likelihood for metastasis it
      should be considered as a differential diagnosis especially in case of suspicious
      intraoperative findings. We report the case of a 73-year-old female patient
      presenting with a hidradenocarcinoma of the wrist. Treatment of
      hidradenocarcinomas is similar to the treatment of sarcomas: The first step is an
      incisional biopsy and obtaining an expert second opinion on the histopathological
      diagnosis as well as staging. The second step is a clear margin resection of the
      tumor and the plastic-surgical reconstruction. A long-term follow-up is mandatory
      to detect potential recurrence or metastasis. 

PMID- 24089305
TI  - [The operative treatment of a bowstring phenomenon of the thumb in childhood:
      case report and literature review].
AB  - INTRODUCTION: The operative treatment of a congenital trigger thumb comprises
      splitting the A1 pulley under conditions of hand surgery. One complication is
      cutting through the A2 pulley. In this case a bowstring phenomenon will result.
      CASE REPORT: We report about the reconstruction of the A2 pulley by using a
      transosseous fixed tendon strip for a now 7-year-old boy with an impressive
      bowstring phenomenon with profound impairment of thumb function and power after
      surgery of a trigger thumb at the age of 2 years. DISCUSSION: The iatrogenic
      splitting of the A2 pulley during the operative treatment of a congenital trigger
      thumb and the treatment of the resulting bowstring phenomenon are not
      sufficiently reflected at the literature. In adulthood, several different methods
      of pulley reconstruction are described. CONCLUSION: In our opinion this technique
      is a safe and easy option to reconstruct the A2 pulley without expensive fibre
      anchors and enables a broad replacement without compromising extension tendons.
      Also outdated bowstring phenomenons are sufficiently stabilised. A good hand
      function with full preservation of finger flexibility and power is ensured as
      well.

PMID- 24089306
TI  - [Idiopathic palmar vein thrombosis of the fingers - rare but relevant].
AB  - Idiopathic thrombosis of palmar finger veins is rare and women suffer from it
      almost exclusively. Synovial cysts, epidermoid inclusion cysts, giant cell
      tumours and haemangiomatous lesions should be considered in the process of
      diagnosis. We present a 56-year-old woman with idiopathic and symptomatic
      thrombosis of palmar finger veins. Using the palmar approach the painful veins
      were identified and excised completely. An uncomplicated wound healing has
      followed with completely unrestricted and painless range of motion. Surgical
      excision of the finger vein thrombosis should be considered if there is
      continuing pain. 

PMID- 24089308
TI  - [Case report: acute carpal tunnel syndrome with prolapse of the median nerve].
AB  - We report a case of an 80-year-old woman with an acute carpal tunnel syndrome.
      This was based on an acute episode of chondrocalcinoses and accompagnied by a
      prolaps of the median nerve into a gap of the forearm fascia as result of a cut
      injury in childhood. 

PMID- 24089307
TI  - [Clawing of the ring and little fingers due to mechanical compression of the deep
      branch of the ulnar nerve at the end of Gyuon's canal by a lipoma].

PMID- 24089309
TI  - [Reconstruction of a broad infected defect zone of the distal part of the radius
      by tractionosteogenesis].
AB  - We report about a reconstruction of a broad infected defect zone by
      tractionosteogenesis and following implantation of a graft from the iliac crest
      and a plate fixation at the distal part of the radius after a gunshot injury by a
      high-velocity bullet. 

PMID- 24089310
TI  - [Benign subcutaneous emphysema caused by a bellows mechanism of the first
      interdigital space].
AB  - We report 2 cases of subcutaneous emphysema after stab wounds of the first
      interdigital space. The first diagnosis of a gas gangrene was not confirmed. We
      hypothese an air incorporation caused by a bellows mechanism. An escape of the
      air may not be possible due to an one-way valve mechanism. The aim of this report
      is to describe criteria to distinguish benign emphysema from emphysema caused by
      infection. 

PMID- 24089311
TI  - Beta2-agonists for exercise-induced asthma.
AB  - BACKGROUND: It is well known that physical exercise can trigger asthma symptoms
      and can induce bronchial obstruction in people without clinical asthma.
      International guidelines on asthma management recommend the use of beta2-agonists
      at any stage of the disease. At present, however, no consensus has been reached
      about the efficacy and safety of beta2-agonists in the pretreatment of exercise
      induced asthma and exercise-induced bronchoconstriction. For the purpose of the
      present review, both of these conditions are referred to by the acronymous EIA,
      independently from the presence of an underlying chronic clinical disease.
      OBJECTIVES: To assess the effects of inhaled short- and long-acting beta2
      agonists, compared with placebo, in the pretreatment of children and adults with
      exercise-induced asthma (or exercise-induced bronchoconstriction). SEARCH
      METHODS: Trials were identified by electronic searching of the Cochrane Airways
      Group Specialised Register of Trials and by handsearching of respiratory journals
      and meetings. Searches are current as of August 2013. SELECTION CRITERIA: We
      included randomised, double-blind, placebo-controlled trials of any study design,
      published in full text, that assessed the effects of inhaled beta2-agonists on
      EIA in adults and children. We excluded studies that did not clearly state
      diagnostic criteria for EIA. DATA COLLECTION AND ANALYSIS: We used standard
      methodological procedures as expected by The Cochrane Collaboration. MAIN
      RESULTS: We included 53 trials consisting of 1139 participants. Forty-eight
      studies used a cross-over design, and five were performed in accordance with a
      parallel-group design. Forty-five studies addressed the effect of a single beta2
      agonist administration, and eight focused on long-term treatment. We addressed
      these two different intervention regimens as different comparisons.Among primary
      outcomes for short-term administration, data on maximum fall in forced expiratory
      volume in 1 second (FEV1) showed a significant protective effect for both short
      acting beta-agonists (SABA) and long-acting beta-agonists (LABA) compared with
      placebo, with a mean difference of -17.67% (95% confidence interval (CI) -19.51%
      to -15.84%, P = 0.00001, 799 participants from 72 studies). The subgroup analysis
      of studies performed in adults compared with those performed in children showed
      high heterogeneity confined to children, despite the comparable mean
      bronchoprotective effect.Secondary outcomes on other pulmonary function
      parameters confirmed a more positive and protective effect of beta2-agonists on
      EIA compared with placebo. Occurrence of side effects was not significantly
      different between beta2-agonists and placebo.Overall evaluation of the included
      long-term studies suggests a beta2-agonist bronchoprotective effect for the first
      dose of treatment. However, long-term use of both SABA and LABA induced the onset
      of tolerance and decreased the duration of drug effect, even after a short
      treatment period. AUTHORS' CONCLUSIONS: Evidence of low to moderate quality shows
      that beta2-agonists, both SABA and LABA, when administered in a single dose, are
      effective and safe in preventing EIA.Long-term regular administration of inhaled
      beta2-agonists induces tolerance and lacks sufficient safety data. This finding
      appears to be of particular clinical relevance in view of the potential for
      prolonged regular use of beta2-agonists as monotherapy in the pretreatment of
      EIA, despite the warnings of drug agencies (FDA, EMA) regarding LABA.

PMID- 24089312
TI  - Pubic rami fractures in the elderly--a neglected injury?
AB  - OBJECTIVE: To evaluate the patient characteristics and natural history of pubic
      rami fractures in geriatric patients, with a special focus on the frequency of
      concomitant posterior pelvic ring lesions and the percentage of secondarily
      operated patients as a result of conservative treatment failure. STUDY DESIGN:
      Retrospective cohort study. Patients were treated in a university hospital that
      is equivalent to a level I Trauma centre. PATIENTS AND METHODS: We analysed 132
      consecutive patients (113 women, 19 men), >65 years old, presenting with low
      energy-trauma pubic rami fractures at our emergency department from January 2009
      to December 2011. RESULTS: Mean age of patients was 84 years (range 66-100).
      Women were affected six times more frequently than men. Almost 30% of patients
      lost their previous independence permanently owing to the injury. Ninety eight
      percent of previously independent patients (community dwellers) required
      temporary hospital care for a median duration of 39 days (interquartile range
      [IQR] 28-52). One-year mortality was 18.5%. A concomitant posterior pelvic ring
      lesion was identified by computed tomography in 54% of patients. In 4% of the
      patients secondary operative fracture stabilisation was performed. DISCUSSION:
      Pubic rami fractures are frequently associated with concomitant posterior pelvic
      ring injuries, making these injuries more unstable than generally assumed. Based
      on this fact and the long duration of hospital stay, more aggressive management
      of these injuries may be considered. The principle aims in this patient
      population are satisfying pain management, early mobilisation, conservation of
      independence and return to previous place of residence.

PMID- 24089314
TI  - [The significance of early evaluation of outpatient integrated care in psychiatry
      taking patients' waiting time as an example].
AB  - Quality indicators are widely used instruments of quality assurance measures to
      illustrate/document/take on record output variables. We here want to review and
      discuss the significance of quality indicators in outpatient integrated
      psychiatric care. Taking patient waiting time as an example, we want to discuss
      the challenges and difficulties to make clear statements about achievements in
      outpatient psychiatric care, and what parameters determine (or temper) these
      results and statements. As a conclusion, we strongly suggest early evaluation in
      the implementation of new ways and structures of patient care to prevent adverse
      outcomes by deficient or erroneous use of quality indicators. 

PMID- 24089313
TI  - Concurrence of anorexia nervosa and Noonan syndrome.
AB  - Noonan syndrome (NS) is a genetic disease inherited in an autosomal dominant
      mode; it presents significant genetic heterogeneity and varying penetrance.
      Mutations have been identified in several genes, and they account for 75% of all
      known cases. The majority of reported mutations are localized on PTPN11 gene,
      which encodes the non-receptor type protein tyrosine phosphatase SHP-2.
      Diagnosis, however, is mainly established after clinical examination. Anorexia
      nervosa (AN) is an eating disorder characterized by fear of gaining weight,
      refusal to maintain normal body weight and distorted perceptions of body image or
      body shape. AN is independently predicted by female sex and feeding problems in
      childhood, whereas NS symptoms include feeding difficulties. No comorbidity
      between NS and AN has been reported to date. The authors reported the case of a
      38-year-old female patient with AN who met the van der Burgt criteria for NS with
      confirmed (a) comorbidity of AN and NS and (b) the absence of the most common
      mutation in PTPN11 and presence of a novel T > A transversion within intron 8-9.

PMID- 24089315
TI  - [Changing attitude towards schizophrenia by psychiatric training of medical
      students].
AB  - OBJECTIVE: The aim of the study was to examine if psychiatric training of medical
      students is appropriate to change their attitude towards schizophrenia and reduce
      stigma. METHOD: Students at Ulm University were asked to answer five questions
      regarding a short case vignette about a patient suffering from schizophrenia at
      the beginning and at the end of a two-week psychiatric training within their
      undergraduate medical education. For this purpose, the Attitudes to Mental
      Illness Questionnaire was used. Differences between attitudes before and after
      the training were examined (paired t-test) and effect sizes were calculated
      (Cohen's d). RESULTS: Data were available of 100 students, 34 men and 66 women.
      There was a statistically significant improvement in the total means of the AMIQ
      score from - 3.09 at the beginning to - 2.31 at the end of the psychiatric
      training. The effect size (d) was 0.35. No significant differences were found
      with respect to the participants' age and gender. CONCLUSION: A two-week
      psychiatric training appears to be an appropriate and effective teaching tool to
      reduce stigma. This is important because health care for patients with
      schizophrenia is strongly influenced by the practitioner's attitude towards them.

PMID- 24089316
TI  - [Transfer-time and -rates from inpatient to outpatient care of mental ill persons
      in Baden Wurttemberg].
AB  - OBJECTIVE: The time of transfer between discharge from inpatient mental health
      care and first contact to the outpatient sector is considered to be an indicator
      for continuity of care. METHODS: This indicator is assessed using health care
      claims data of one of the mayor health insurances in Baden-Wurttemberg, Germany.
      RESULTS: About 80 % of cases with the diagnosis of a defined mental disorder
      sought outpatient care at general or mental health practitioners within six
      months from discharge. 50 % of them did so within six days, 75 % within three
      weeks. The majority sought outpatient care at general practitioners. Cases that
      sought care in outpatient clinics specialized for severe mental illness (SMI)
      could not be considered in the data. However, considering them by estimation, the
      rate of cases with SMI seeking outpatient care at mental health practitioners
      within six months from discharge estimated to be at least 70 %. CONCLUSIONS:
      General practitioners are an important source for aftercare of mentally ill
      people discharged from inpatient care. Time of transfer as an indicator can be
      predominantly assessed by using health claims data in Germany.

PMID- 24089317
TI  - [Establishing a team-scoring model for socio-emotional development of patients
      with intellectual disabilities].
AB  - OBJECTIVES: We know from daily experience in the care of people with intellectual
      disabilities that the usually applied bio-psycho-social model is not sufficient
      in the psychiatric treatment of that patient-group. A fourth dimension
      considering cognitive and socio-emotional development should be added. A specific
      algorithm for evaluating the emotional level of a person (called "SEO") has
      demonstrated its effectiveness. Aim of this study is to test its feasibility in
      everyday practice in a hospital team of a psychiatric ward. METHODS: The SEO was
      used to evaluate 18 patients with intellectual disability by a multi-professional
      team in a psychiatric hospital ward. The time for completing the SEO was measured
      within a time period of 8 weeks. Additionally, the influence on patients' problem
      behaviour in the time period after completion of the SEO was measured. RESULTS:
      The average time needed for completing one SEO was 11 minutes. After the second
      week, there was no further shortening of the time necessary for completion of the
      SEO, nor was their any further improvement in the quality of scoring the SEO by
      the team. After completion of the SEO, behavioral problems of the patients
      improved significantly in the following time period. CONCLUSION: The SEO seems to
      be time-economic and feasible for evaluating the socio-emotional development,
      which can be well integrated in the routine of a psychiatric hospital team. The
      benefit for patients is the significant reduction of problem behaviour after SEO
      evaluation in general.

PMID- 24089318
TI  - [Determinants of direct cost in schizophrenia patients with persistent positive
      symptoms].
AB  - OBJECTIVE: To analyze direct costs and cost determinants in psychotic patients
      with persistent positive symptoms (PPS). METHODS: A total of 330 patients with
      PPS were recruited via 6 university clinics and interviewed about service
      utilization in the previous 3 months. After monetary valuation, costs were
      analyzed via generalized linear mixed models with gamma distribution and log-link
      function to identify determinants of direct costs. RESULTS: The mean costs were
      7,065 ? and resulted predominantly from psychiatric hospital care (63 %),
      assisted living (17 %) and complementary services (8 %). We found statistically
      significant associations between direct costs and an increasing score of the
      negative subscale of the Positive and Negative Syndrome Scale (+ 2,484 ? per
      point, p < 0.001) and experiencing less than one social contact per week (- 2,272
      ?, p = 0.003). CONCLUSION: PPS incurred substantial direct costs which primarily
      resulted from hospital treatment, and were strongly associated with symptom
      severity.

PMID- 24089319
TI  - [Measurement invariance of the German version of the Center for Epidemiological
      Studies Depression Scale (CES-D 20) among males and females with and without a
      history of migration].
AB  - OBJECTIVE: The measurement invariance of the German version of the Center of
      Epidemiological Studies Depression scale (CES-D 20) among men and women with and
      without migration background has not been studied yet. METHODS: A total of 2786
      employed persons without (female n = 1772, male n = 598) and with an immigrant
      background (female n = 301, male n = 115) were included in the study. The multi
      group confirmatory factor analysis was used to test for the strong factorial
      invariance and to estimate latent mean differences. RESULTS: The factorial
      structure is invariat 1) across the female sub-sample, full scalar invariance is
      achieved, 2) compared to male non-migrants and female sub-sample, partial scalar
      invariance is achieved. 3) The male migrants show a different, three-factor
      structure with a mix-factor of depressive affect/somatic complaints. 4) Female
      migrants have significantly higher latent mean values in subscales. CONCLUSION:
      The measurement invariance of the German CES-D 20 is given to that extent that
      meaningful comparisons in correlative coefficient and latent mean values can be
      made.

PMID- 24089320
TI  - [Optimized quality of care for affective disorders by health insurance-based case
      management: a controlled cost-study].
AB  - OBJECTIVE: Improvement of depression treatment by health insurance based case
      management. Criteria of improvement were a higher treatment rate of patients
      suffering from affective disorders or depression by psychiatrists or
      psychotherapists than by general practitioners or family doctors and sickness
      fund payments. METHODS: Training of health insurance account managers
      (characteristics of depression, counselling and, case management techniques).
      Evaluation of outcomes during 12-months against a control group of account
      managers without training. RESULTS: Intervention group: 87.8 % patients with in
      average 13.5 contacts to psychiatrists or psychotherapists; control group: 82.6 %
      patients with 11.8 contacts. The difference was statistically significant. Health
      insurance payments did not differ. CONCLUSIONS: A higher treatment rate by
      psychiatrists and psychotherapists can be achieved by health insurance-based case
      management without a cost-increase.

PMID- 24089321
TI  - [Sickness funds' activities for early detection, prevention and health promotion
      in depressive disorders].
AB  - OBJECTIVE: We analyzed programs managed by the ten biggest social health
      insurance companies in Germany that aim at early detection, prevention, and
      promotion of health in depression. METHODS: We conducted interviews with the
      responsible managers and studied relevant web sites. RESULTS: The content of
      these programs ranges from internet-based offers to relaxation techniques. There
      is very little information publicly available on the results of these programs;
      the same holds true for the number of participants, efficiency, and cooperation
      with physicians. CONCLUSION: There is a strong need to investigate results and
      efficiency of the programs.

PMID- 24089322
TI  - [Multiple-choice vocabulary intelligence test MWT in schizophrenia: valid measure
      of premorbid intelligence?].
AB  - OBJECTIVE: The multiple-choice vocabulary intelligence test MWT (Mehrfachwahl
      Wortschatz-Intelligenztest) as a measure of premorbid IQ is widely used in
      clinical practice and research in Germany. The study examined whether the MWT is
      actually insensitive to brain dysfunction and psychopathology in patients with
      schizophrenia. METHOD: 81 post-acute patients with schizophrenia and 27 matched
      healthy controls completed the MWT at two points in time. At baseline, we further
      applied a neuropsychological test battery and a psychopathology rating. RESULTS:
      The multiple linear regression analysis showed that the MWT-IQ of patients is
      significantly confounded by neuropsychological dysfunctions and psychopathology.
      The repeated measurement ANOVA pointed to a significant recovery effect of the
      MWT-IQ during clinical remission in the patient group. CONCLUSION: The results
      question the validity of the MWT as a measure of premorbid IQ in schizophrenia.

PMID- 24089323
TI  - [Nephrotoxicity and long-term treatment with lithium].
AB  - With particular focus on clinical, pathophysiologic and epidemiologic aspects
      this systematic review article presents the available data on nephrotoxic effects
      of a long-term treatment with lithium. Lithium may lead to tubular dysfunction
      (LITD = nephrogenic diabetes insipidus, hyperchloremic metabolic acidosis,
      increased natriuresis) and lithium-induced nephropathy (LIN) with reduced
      glomerular filtration rate (GFR). The histopathologic finding of LIN is chronic
      tubulo-interstitial nephritis. LITD frequently presents with polydipsia/-uria and
      reduced urine osmolality, while LIN features a wide clinical spectrum ranging
      from clinically asymptomatic presentations with reduced GFR to end-stage renal
      failure. LIN seems to feature slow progression and is significantly less frequent
      than LITD. Regular monitoring of renal function is indispensable for patients
      treated with lithium. Patients with reduced GFR under treatment with lithium
      should always be presented to a nephrologist. Currently, there are no guidelines
      for the handling of patients with LIN and ongoing treatment with lithium. Thus,
      regarding continuation of lithium-treatment an individual benefit/risk assessment
      is necessary. 

PMID- 24089324
TI  - Poly (ADP-ribose) polymerase-1 is a key mediator of liver inflammation and
      fibrosis.
AB  - Poly (ADP-ribose) polymerase 1 (PARP-1) is a constitutive enzyme, the major
      isoform of the PARP family, which is involved in the regulation of DNA repair,
      cell death, metabolism, and inflammatory responses. Pharmacological inhibitors of
      PARP provide significant therapeutic benefits in various preclinical disease
      models associated with tissue injury and inflammation. However, our understanding
      the role of PARP activation in the pathophysiology of liver inflammation and
      fibrosis is limited. In this study we investigated the role of PARP-1 in liver
      inflammation and fibrosis using acute and chronic models of carbon tetrachloride
      (CCl4 )-induced liver injury and fibrosis, a model of bile duct ligation (BDL)
      induced hepatic fibrosis in vivo, and isolated liver-derived cells ex vivo.
      Pharmacological inhibition of PARP with structurally distinct inhibitors or
      genetic deletion of PARP-1 markedly attenuated CCl4 -induced hepatocyte death,
      inflammation, and fibrosis. Interestingly, the chronic CCl4 -induced liver injury
      was also characterized by mitochondrial dysfunction and dysregulation of numerous
      genes involved in metabolism. Most of these pathological changes were attenuated
      by PARP inhibitors. PARP inhibition not only prevented CCl4 -induced chronic
      liver inflammation and fibrosis, but was also able to reverse these pathological
      processes. PARP inhibitors also attenuated the development of BDL-induced hepatic
      fibrosis in mice. In liver biopsies of subjects with alcoholic or hepatitis B
      induced cirrhosis, increased nitrative stress and PARP activation was noted.
      CONCLUSION: The reactive oxygen/nitrogen species-PARP pathway plays a
      pathogenetic role in the development of liver inflammation, metabolism, and
      fibrosis. PARP inhibitors are currently in clinical trials for oncological
      indications, and the current results indicate that liver inflammation and liver
      fibrosis may be additional clinical indications where PARP inhibition may be of
      translational potential.

PMID- 24089325
TI  - Addition of anti-leukotriene agents to inhaled corticosteroids in children with
      persistent asthma.
AB  - BACKGROUND: In the treatment of children with mild persistent asthma, low-dose
      inhaled corticosteroids (ICS) are recommended as the preferred monotherapy
      (referred to as step 2 of therapy). In children with inadequate asthma control on
      low doses of ICS (step 2), asthma management guidelines recommend adding an anti
      leukotriene agent to existing ICS as one of three therapeutic options to
      intensify therapy (step 3). OBJECTIVES: To compare the efficacy and safety of the
      combination of anti-leukotriene agents and ICS to the use of the same, an
      increased, or a tapering dose of ICS in children and adolescents with persistent
      asthma who remain symptomatic despite the use of maintenance ICS. In addition, we
      wished to determine the characteristics of people or treatments, if any, that
      influenced the magnitude of response attributable to the addition of anti
      leukotrienes. SEARCH METHODS: We identified trials from the Cochrane Airways
      Group Specialised Register of Trials (CAGR), which were derived from systematic
      searches of bibliographic databases including the Cochrane Central Register of
      Controlled Trials (CENTRAL), MEDLINE, EMBASE, PsycINFO, AMED, and CINAHL; and the
      handsearching of respiratory journals and meeting abstracts, as well as the
      www.clinicaltrials.gov website. The search was conducted until January 2013.
      SELECTION CRITERIA: We considered for inclusion randomised controlled trials
      (RCTs) conducted in children and adolescents, aged one to 18 years, with asthma,
      who remained symptomatic despite the use of a stable maintenance dose of ICS and
      in whom anti-leukotrienes were added to the ICS if they were compared to the
      same, an increased, or a tapering dose of ICS for at least four weeks. DATA
      COLLECTION AND ANALYSIS: We used standard methods expected by The Cochrane
      Collaboration. MAIN RESULTS: Five paediatric (parallel group or cross-over)
      trials met the inclusion criteria. We considered two (40%) trials to be at a low
      risk of bias. Four published trials, representing 559 children (aged >= six
      years) and adolescents with mild to moderate asthma, contributed data to the
      review. No trial enrolled preschoolers. All trials used montelukast as the anti
      leukotriene agent administered for between four and 16 weeks. Three trials
      evaluated the combination of anti-leukotrienes and ICS compared to the same dose
      of ICS alone (step 3 versus step 2). No statistically significant group
      difference was observed in the only trial reporting participants with
      exacerbations requiring oral corticosteroids over four weeks (N = 268
      participants; risk ratio (RR) 0.80, 95% confidence interval (CI) 0.34 to 1.91).
      There was also no statistically significant difference in percentage change in
      FEV1 (forced expiratory volume in 1 second) with mean difference (MD) 1.3 (95% CI
      -0.09 to 2.69) in this trial, but a significant group difference was observed in
      the morning (AM) and evening (PM) peak expiratory flow rates (PEFR): N = 218
      participants; MD 9.70 L/min (95% CI 1.27 to 18.13) and MD 10.70 (95% CI 2.41 to
      18.99), respectively. One trial compared the combination of anti-leukotrienes and
      ICS to a higher-dose of ICS (step 3 versus step 3). No significant group
      difference was observed in this trial for participants with exacerbations
      requiring rescue oral corticosteroids over 16 weeks (N = 182 participants; RR
      0.82, 95% CI 0.54 to 1.25), nor was there any significant difference in
      exacerbations requiring hospitalisation. There was no statistically significant
      group difference in withdrawals overall or because of any cause with either
      protocol. No trial explored the impact of adding anti-leukotrienes as a means to
      taper the dose of ICS. AUTHORS' CONCLUSIONS: The addition of anti-leukotrienes to
      ICS is not associated with a statistically significant reduction in the need for
      rescue oral corticosteroids or hospital admission compared to the same or an
      increased dose of ICS in children and adolescents with mild to moderate asthma.
      Although anti-leukotrienes have been licensed for use in children for over 10
      years, the paucity of paediatric trials, the absence of data on preschoolers, and
      the variability in the reporting of relevant clinical outcomes considerably limit
      firm conclusions. At present, there is no firm evidence to support the efficacy
      and safety of anti-leukotrienes as add-on therapy to ICS as a step-3 option in
      the therapeutic arsenal for children with uncontrolled asthma symptoms on low
      dose ICS.

PMID- 24089326
TI  - Massachusetts health care reform and reduced racial disparities in minimally
      invasive surgery.
AB  - IMPORTANCE: Racial disparities in receipt of minimally invasive surgery (MIS)
      persist in the United States and have been shown to also be associated with a
      number of driving factors, including insurance status. However, little is known
      as to how expanding insurance coverage across a population influences disparities
      in surgical care. OBJECTIVE: To evaluate the impact of Massachusetts health care
      reform on racial disparities in MIS. DESIGN, SETTING, AND PARTICIPANTS: A
      retrospective cohort study assessed the probability of undergoing MIS vs an open
      operation for nonwhite patients in Massachusetts compared with 6 control states.
      All discharges (n = 167,560) of nonelderly white, black, or Latino patients with
      government insurance (Medicaid or Commonwealth Care insurance) or no insurance
      who underwent a procedure for acute appendicitis or acute cholecystitis at
      inpatient hospitals between January 1, 2001, and December 31, 2009, were
      assessed. Data are from the Hospital Cost and Utilization Project State Inpatient
      Databases. INTERVENTION: The 2006 Massachusetts health care reform, which
      expanded insurance coverage for government-subsidized, self-pay, and uninsured
      individuals in Massachusetts. MAIN OUTCOMES AND MEASURES: Adjusted probability of
      undergoing MIS and difference-in-difference estimates. RESULTS: Prior to the 2006
      reform, Massachusetts nonwhite patients had a 5.21-percentage point lower
      probability of MIS relative to white patients (P < .001). Nonwhite patients in
      control states had a 1.39-percentage point lower probability of MIS (P = .007).
      After reform, nonwhite patients in Massachusetts had a 3.71-percentage point
      increase in the probability of MIS relative to concurrent trends in control
      states (P = .01). After 2006, measured racial disparities in MIS resolved in
      Massachusetts, with nonwhite patients having equal probability of MIS relative to
      white patients (0.06 percentage point greater; P = .96). However, nonwhite
      patients in control states without health care reform have a persistently lower
      probability of MIS relative to white patients (3.19 percentage points lower; P <
      .001). CONCLUSIONS AND RELEVANCE: The 2006 Massachusetts insurance expansion was
      associated with an increased probability of nonwhite patients undergoing MIS and
      resolution of measured racial disparities in MIS.

PMID- 24089327
TI  - Overproduction of NOX-derived ROS in AML promotes proliferation and is associated
      with defective oxidative stress signaling.
AB  - Excessive production of reactive oxygen species (ROS) is frequently observed in
      cancer and is known to strongly influence hematopoietic cell function. Here we
      report that extracellular ROS production is strongly elevated (mean >10-fold) in
      >60% of acute myeloid leukemia (AML) patients and that this increase is
      attributable to constitutive activation of nicotinamide adenine dinucleotide
      phosphate oxidases (NOX). In contrast, overproduction of mitochondrial ROS was
      rarely observed. Elevated ROS was found to be associated with lowered glutathione
      levels and depletion of antioxidant defense proteins. We also show for the first
      time that the levels of ROS generated were able to strongly promote the
      proliferation of AML cell lines, primary AML blasts, and, to a lesser extent,
      normal CD34(+) cells, and that the response to ROS is limited by the activation
      of the oxidative stress pathway mediated though p38(MAPK). Consistent with this,
      we observed that p38(MAPK) responses were attenuated in patients expressing high
      levels of ROS. These data show that overproduction of NOX-derived ROS can promote
      the proliferation of AML blasts and that they also develop mechanisms to suppress
      the stress signaling that would normally limit this response. Together these
      adaptations would be predicted to confer a competitive advantage to the leukemic
      clone. 

PMID- 24089328
TI  - A Mendelian predisposition to B-cell lymphoma caused by IL-10R deficiency.
AB  - Monogenic interleukin-10 (IL-10) and IL-10 receptor (IL-10R) deficiencies cause
      very early onset severe inflammatory bowel disease. Here, we report that 5
      patients with an IL-10R1 (n = 1) or IL-10R2 (n = 4) deficiency developed B-cell
      non-Hodgkin lymphoma between the ages of 5 and 6 years (which was recurrent in 1
      patient). These lymphomas had some of the characteristics of diffuse large B-cell
      lymphomas and contained monoclonal, Epstein-Barr virus-negative germinal center B
      cells. The tumors displayed a remarkably homogeneous signature, with original
      activation of the nuclear factor kappaB pathway and a decrease in intratumor T
      cell infiltration. Hence, IL-10R deficiency is associated with a high risk of
      developing B-cell lymphoma. Our results revealed an unexpected role of the IL-10R
      pathway in lymphomagenesis. 

PMID- 24089329
TI  - Origin and outcome of multiple pregnancies in Bern, Switzerland, 1995-2006 and
      the current proposal of the Swiss parliament to revise the Swiss law of
      reproductive medicine: Switzerland quo vadis?
AB  - INTRODUCTION: Infertility treatments are a major source of the increase in
      multiple pregnancies (MPs). AIMS: The aims of the present study were (1.) to
      investigate the origin and maternal/neonatal outcomes of MP and (2.) to review
      the different measures that can be adopted to reduce these serious complications.
      METHODS: The study included all women with multiple births between 1 January 1995
      and 31 December 2006 at the University Hospital of Bern, Switzerland. The
      outcomes associated with the various origins of MP (natural conception, ovarian
      stimulation [OS]--in-vitro fertilisation [IVF-ICSI]) were analysed using a
      multinomial logistic regression model. An analysis of the Swiss law on
      reproductive medicine and its current proposed revision, as well as a literature
      review using Pubmed, was carried out. RESULTS: A total of 592 MP were registered,
      91% (n = 537) resulted in live births. There was significantly more
      neonatal/maternal morbidity in MP after OS compared with natural conception and
      even with the IVF-ICSI group. With a policy of elective single embryo transfer
      (eSET), twin rates after IVF-ICSI can be reduced to <5% and triplets to <1%.
      CONCLUSIONS: After OS, more triplets are found and the outcome of MP is worse. MP
      is known to be associated with morbidity, mortality, and economic and social
      risks. To counteract these complications (1.) better training for physicians
      performing OS should be encouraged and (2.) the Swiss law on reproductive
      medicine needs to be changed, with the introduction of eSET policies. This would
      lead to a dramatic decrease in neonatal and maternal morbidity/mortality as well
      as significant cost reductions for the Swiss healthcare system.

PMID- 24089330
TI  - A role for epigenetic inheritance in modern evolutionary theory? A comment in
      response to Dickins and Rahman.

PMID- 24089331
TI  - An ITS-based phylogenetic framework for the genus Vorticella: finding the
      molecular and morphological gaps in a taxonomically difficult group.
AB  - Vorticella includes more than 100 currently recognized species and represents one
      of the most taxonomically challenging genera of ciliates. Molecular phylogenetic
      analysis of Vorticella has been performed so far with only sequences coding for
      small subunit ribosomal RNA (SSU rRNA); only a few of its species have been
      investigated using other genetic markers owing to a lack of similar sequences for
      comparison. Consequently, phylogenetic relationships within the genus remain
      unclear, and molecular discrimination between morphospecies is often difficult
      because most regions of the SSU rRNA gene are too highly conserved to be helpful.
      In this paper, we move molecular systematics for this group of ciliates to the
      infrageneric level by sequencing additional molecular markers-fast-evolving
      internal transcribed spacer (ITS) regions-in a broad sample of 66 individual
      samples of 28 morphospecies of Vorticella collected from Asia, North America and
      Europe. Our phylogenies all featured two strongly supported, highly divergent,
      paraphyletic clades (I, II) comprising the morphologically defined genus
      Vorticella. Three major lineages made up clade I, with a relatively well-resolved
      branching order in each one. The marked divergence of clade II from clade I
      confirms that the former should be recognized as a separate taxonomic unit as
      indicated by SSU rRNA phylogenies. We made the first attempt to elucidate
      relationships between species in clade II using both morphological and multi-gene
      approaches, and our data supported a close relationship between some
      morphospecies of Vorticella and Opisthonecta, indicating that relationships
      between species in the clade are far more complex than would be expected from
      their morphology. Different patterns of helix III of ITS2 secondary structure
      were clearly specific to clades and subclades of Vorticella and, therefore, may
      prove useful for resolving phylogenetic relationships in other groups of
      ciliates. 

PMID- 24089333
TI  - Headwaters are critical reservoirs of microbial diversity for fluvial networks.
AB  - Streams and rivers form conspicuous networks on the Earth and are among nature's
      most effective integrators. Their dendritic structure reaches into the
      terrestrial landscape and accumulates water and sediment en route from abundant
      headwater streams to a single river mouth. The prevailing view over the last
      decades has been that biological diversity also accumulates downstream. Here, we
      show that this pattern does not hold for fluvial biofilms, which are the dominant
      mode of microbial life in streams and rivers and which fulfil critical ecosystem
      functions therein. Using 454 pyrosequencing on benthic biofilms from 114 streams,
      we found that microbial diversity decreased from headwaters downstream and
      especially at confluences. We suggest that the local environment and biotic
      interactions may modify the influence of metacommunity connectivity on local
      biofilm biodiversity throughout the network. In addition, there was a high degree
      of variability in species composition among headwater streams that could not be
      explained by geographical distance between catchments. This suggests that the
      dendritic nature of fluvial networks constrains the distributional patterns of
      microbial diversity similar to that of animals. Our observations highlight the
      contributions that headwaters make in the maintenance of microbial biodiversity
      in fluvial networks. 

PMID- 24089332
TI  - Predictive systems ecology.
AB  - Human societies, and their well-being, depend to a significant extent on the
      state of the ecosystems that surround them. These ecosystems are changing rapidly
      usually in response to anthropogenic changes in the environment. To determine the
      likely impact of environmental change on ecosystems and the best ways to manage
      them, it would be desirable to be able to predict their future states. We present
      a proposal to develop the paradigm of predictive systems ecology, explicitly to
      understand and predict the properties and behaviour of ecological systems. We
      discuss the necessary and desirable features of predictive systems ecology
      models. There are places where predictive systems ecology is already being
      practised and we summarize a range of terrestrial and marine examples.
      Significant challenges remain but we suggest that ecology would benefit both as a
      scientific discipline and increase its impact in society if it were to embrace
      the need to become more predictive. 

PMID- 24089334
TI  - A comparative collision-based analysis of human gait.
AB  - This study compares human walking and running, and places them within the context
      of other mammalian gaits. We use a collision-based approach to analyse the
      fundamental dynamics of the centre of mass (CoM) according to three angles
      derived from the instantaneous force and velocity vectors. These dimensionless
      angles permit comparisons across gait, species and size. The collision angle Phi,
      which is equivalent to the dimensionless mechanical cost of transport CoTmech, is
      found to be three times greater during running than walking of humans. This
      threefold difference is consistent with previous studies of walking versus
      trotting of quadrupeds, albeit tends to be greater in the gaits of humans and
      hopping bipeds than in quadrupeds. Plotting the collision angle Phi together with
      the angles of the CoM force vector Theta and velocity vector Lambda results in
      the functional grouping of bipedal and quadrupedal gaits according to their CoM
      dynamics-walking, galloping and ambling are distinguished as separate gaits that
      employ collision reduction, whereas trotting, running and hopping employ little
      collision reduction and represent more of a continuum that is influenced by
      dimensionless speed. Comparable with quadrupedal mammals, collision fraction (the
      ratio of actual to potential collision) is 0.51 during walking and 0.89 during
      running, indicating substantial collision reduction during walking, but not
      running, of humans. 

PMID- 24089336
TI  - Multiple pathways mediate the sex-peptide-regulated switch in female Drosophila
      reproductive behaviours.
AB  - Male-derived sex-peptide (SP) induces profound changes in the behaviour of
      Drosophila females, resulting in decreased receptivity to further mating and
      increased egg laying. SP can mediate the switch in female reproductive behaviours
      via a G protein-coupled receptor, SPR, in neurons expressing fruitless, doublesex
      and pickpocket. Whether SPR is the sole receptor and whether SP induces the
      postmating switch in a single pathway has not, to our knowledge been tested. Here
      we report that the SP response can be induced in the absence of SPR when SP is
      ectopically expressed in neurons or when SP, transferred by mating, can access
      neurons through a leaky blood brain barrier. Membrane-tethered SP can induce
      oviposition via doublesex, but not fruitless and pickpocket neurons in SPR mutant
      females. Although pickpocket and doublesex neurons rely on G(o) signalling to
      reduce receptivity and induce oviposition, G(o) signalling in fruitless neurons
      is required only to induce oviposition, but not to reduce receptivity. Our
      results show that SP's action in reducing receptivity and inducing oviposition
      can be separated in fruitless and doublesex neurons. Hence, the SP-induced
      postmating switch incorporates shared, but also distinct circuitry of fruitless,
      doublesex and pickpocket neurons and additional receptors. 

PMID- 24089337
TI  - The impact of specific and non-specific immunity on the ecology of Streptococcus
      pneumoniae and the implications for vaccination.
AB  - More than 90 capsular serotypes of Streptococcus pneumoniae coexist despite
      competing for nasopharyngeal carriage and a gradient in fitness. The underlying
      mechanisms for this are poorly understood and make assessment of the likely
      population impact of vaccination challenging. We use an individual-based
      simulation model to generalize widely used deterministic models for pneumococcal
      competition and show that in these models short-term serotype-specific and
      serotype non-specific immunity could constitute the mechanism governing between
      host competition and coexistence. We find that non-specific immunity induces
      between-host competition and that serotype-specific immunity limits a type's
      competitive advantage and allows stable coexistence of multiple serotypes.
      Serotypes carried at low prevalence show high variance in carriage levels, which
      would result in apparent outbreaks if they were highly pathogenic. Vaccination
      against few serotypes can lead to elimination of the vaccine types and induces
      replacement by others. However, in simulations where the elimination of the
      targeted types is achieved only by a combination of vaccine effects and the
      competitive pressure of the non-vaccine types, a universal vaccine with similar
      type-specific effectiveness can fail to eliminate pneumococcal carriage and
      offers limited herd immunity. Hence, if vaccine effects are insufficient to
      control the majority of serotypes at the same time, then exploiting the
      competitive pressure by selective vaccination can help control the most
      pathogenic serotypes. 

PMID- 24089338
TI  - Short-term disturbance by a commercial two-dimensional seismic survey does not
      lead to long-term displacement of harbour porpoises.
AB  - Assessments of the impact of offshore energy developments are constrained because
      it is not known whether fine-scale behavioural responses to noise lead to broader
      scale displacement of protected small cetaceans. We used passive acoustic
      monitoring and digital aerial surveys to study changes in the occurrence of
      harbour porpoises across a 2000 km(2) study area during a commercial two
      dimensional seismic survey in the North Sea. Acoustic and visual data provided
      evidence of group responses to airgun noise from the 470 cu inch array over
      ranges of 5-10 km, at received peak-to-peak sound pressure levels of 165-172 dB
      re 1 uPa and sound exposure levels (SELs) of 145-151 dB re 1 uPa(2) s(-1).
      However, animals were typically detected again at affected sites within a few
      hours, and the level of response declined through the 10 day survey. Overall,
      acoustic detections decreased significantly during the survey period in the
      impact area compared with a control area, but this effect was small in relation
      to natural variation. These results demonstrate that prolonged seismic survey
      noise did not lead to broader-scale displacement into suboptimal or higher-risk
      habitats, and suggest that impact assessments should focus on sublethal effects
      resulting from changes in foraging performance of animals within affected sites. 

PMID- 24089339
TI  - Differential reproductive responses to stress reveal the role of life-history
      strategies within a species.
AB  - Life-history strategies describe that 'slow'- in contrast to 'fast'-living
      species allocate resources cautiously towards reproduction to enhance survival.
      Recent evidence suggests that variation in strategies exists not only among
      species but also among populations of the same species. Here, we examined the
      effect of experimentally induced stress on resource allocation of breeding
      seabirds in two populations with contrasting life-history strategies: slow-living
      Pacific and fast-living Atlantic black-legged kittiwakes. We tested the
      hypothesis that reproductive responses in kittiwakes under stress reflect their
      life-history strategies. We predicted that in response to stress, Pacific
      kittiwakes reduce investment in reproduction compared with Atlantic kittiwakes.
      We exposed chick-rearing kittiwakes to a short-term (3-day) period of increased
      exogenous corticosterone (CORT), a hormone that is released during food
      shortages. We examined changes in baseline CORT levels, parental care and effects
      on offspring. We found that kittiwakes from the two populations invested
      differently in offspring when facing stress. In response to elevated CORT,
      Pacific kittiwakes reduced nest attendance and deserted offspring more readily
      than Atlantic kittiwakes. We observed lower chick growth, a higher stress
      response in offspring and lower reproductive success in response to CORT
      implantation in Pacific kittiwakes, whereas the opposite occurred in the
      Atlantic. Our findings support the hypothesis that life-history strategies
      predict short-term responses of individuals to stress within a species. We
      conclude that behaviour and physiology under stress are consistent with trade-off
      priorities as predicted by life-history theory. We encourage future studies to
      consider the pivotal role of life-history strategies when interpreting inter
      population differences of animal responses to stressful environmental events. 

PMID- 24089340
TI  - Mammal disparity decreases during the Cretaceous angiosperm radiation.
AB  - Fossil discoveries over the past 30 years have radically transformed traditional
      views of Mesozoic mammal evolution. In addition, recent research provides a more
      detailed account of the Cretaceous diversification of flowering plants. Here, we
      examine patterns of morphological disparity and functional morphology associated
      with diet in early mammals. Two analyses were performed: (i) an examination of
      diversity based on functional dental type rather than higher-level taxonomy, and
      (ii) a morphometric analysis of jaws, which made use of modern analogues, to
      assess changes in mammalian morphological and dietary disparity. Results
      demonstrate a decline in diversity of molar types during the mid-Cretaceous as
      abundances of triconodonts, symmetrodonts, docodonts and eupantotherians
      diminished. Multituberculates experience a turnover in functional molar types
      during the mid-Cretaceous and a shift towards plant-dominated diets during the
      late Late Cretaceous. Although therians undergo a taxonomic expansion coinciding
      with the angiosperm radiation, they display small body sizes and a low level of
      morphological disparity, suggesting an evolutionary shift favouring small
      insectivores. It is concluded that during the mid-Cretaceous, the period of rapid
      angiosperm radiation, mammals experienced both a decrease in morphological
      disparity and a functional shift in dietary morphology that were probably related
      to changing ecosystems. 

PMID- 24089341
TI  - Experimental evidence that extra-pair mating drives asymmetrical introgression of
      a sexual trait.
AB  - Theory suggests that traits under positive selection may introgress
      asymmetrically across a hybrid zone, potentially driven by sexual selection. Two
      subspecies of the red-backed fairy-wren (Malurus melanocephalus) differ primarily
      in a sexual signal used in mate choice-red versus orange male back plumage colour
      but phylogeographic analyses suggest asymmetrical introgression of red plumage
      into the genetic background of the orange subspecies. We hypothesized that this
      asymmetrical introgression may be facilitated by sexual selection if red males
      have a mating advantage over orange males. We tested this hypothesis with
      correlational data and a plumage manipulation experiment where we reddened the
      back plumage of a subset of orange males to mimic males of the red subspecies.
      There was no correlational evidence of a mating advantage to naturally redder
      males in this population. Experimentally reddened males sired a similar amount of
      within-pair young and lost paternity at the same rate as orange males, but they
      sired significantly more extra-pair young, leading to substantially higher total
      reproductive success. Thus, we conclude that sexual selection via extra-pair
      mating is a likely mechanism responsible for the asymmetrical introgression of
      plumage colour in this system, and is potentially driven by a sensory bias for
      the red plumage signal. 

PMID- 24089342
TI  - A new Late Eocene primate from the Krabi Basin (Thailand) and the diversity of
      Palaeogene anthropoids in southeast Asia.
AB  - According to the most recent discoveries from the Middle Eocene of Myanmar and
      China, anthropoid primates originated in Asia rather than in Africa, as was
      previously considered. But the Asian Palaeogene anthropoid community remains
      poorly known and inadequately sampled, being represented only from China,
      Myanmar, Pakistan and Thailand. Asian Eocene anthropoids can be divided into two
      distinct groups, the stem group eosimiiforms and the possible crown group
      amphipithecids, but the phylogenetic relationships between these two groups are
      not well understood. Therefore, it is critical to understand their evolutionary
      history and relationships by finding additional fossil taxa. Here, we describe a
      new small-sized fossil anthropoid primate from the Late Eocene Krabi locality in
      Thailand, Krabia minuta, which shares several derived characters with the
      amphipithecids. It displays several unique dental characters, such as extreme
      bunodonty and reduced trigon surface area, that have never been observed in other
      Eocene Asian anthropoids. These features indicate that morphological adaptations
      were more diversified among amphipithecids than was previously expected, and
      raises the problem of the phylogenetic relations between the crown anthropoids
      and their stem group eosimiiforms, on one side, and the modern anthropoids, on
      the other side. 

PMID- 24089343
TI  - The utility of a guidelinerTM catheter in retrograde percutaneous coronary
      intervention of a chronic total occlusion with reverse cart-the "capture"
      technique.
AB  - The hybrid approach to percutaneous treatment of chronic total occlusion (CTO) of
      coronary arteries requires both antegrade and retrograde skillsets. In the
      retrograde approach, wire externalization through the antegrade guide catheter
      often requires the use of a short donor guide catheter and a long (>150 cm) micro
      catheter. Despite this there are occasions where the micro-catheter is unable to
      reach the anterograde guide catheter because of long collateral channels
      particularly when the retrograde limb involves a bypass graft. We report such a
      case where retrograde intervention was used to treat a right coronary artery
      (RCA) CTO in a patient with stable angina. The retrograde limb involved a
      saphenous vein graft to the native circumflex artery, which in turn provided
      collateral channels to the distal RCA. After performing reverse controlled
      anterograde and retrograde sub-intimal tracking (CART), the retrograde micro
      catheter was only able to reach the mid RCA. To solve this, a GuidelinerTM
      catheter was passed on the antegrade wire and successfully advanced over and
      "captured" the retrograde micro-catheter. Wire externalization was then completed
      and the RCA was subsequently stented with a good final angiographic result. This
      case illustrates a novel approach to completing wire externalization and provides
      a further indication for the role of the GuidelinerTM catheter in treating CTOs.

PMID- 24089344
TI  - Quantified pathologic response assessed as residual tumor burden is a predictor
      of recurrence-free survival in patients with rectal cancer who undergo resection
      after neoadjuvant chemoradiotherapy.
AB  - BACKGROUND: The current study was conducted to determine whether quantified
      pathologic response assessed as a percentage of residual tumor cells is
      predictive of recurrence-free survival (RFS) in patients with rectal cancer.
      METHODS: The authors studied 251 patients with rectal adenocarcinoma who were
      treated with neoadjuvant chemoradiation and radical resection. Quantified
      pathologic response was defined as an estimated percentage of residual cancer
      cells in relation to the tumor bed: complete, no residual cancer cells; near
      complete, <= 5% residual cancer cells; major, > 5%, and < 50% residual cancer
      cells; and minor, >= 50% residual cancer cells. The reproducibility of quantified
      pathologic response between 2 pathologists was assessed using tumors from 55
      randomly selected patients who did not demonstrate a complete response. RESULTS:
      Pathologic response was complete in 21% of patients, near-complete in 20% of
      patients, major in 37% of patients, and minor in 22% of patients. Nineteen
      percent of patients had ypT0N0 disease, 27% had ypT1-2N0 disease, 21% had ypT3
      4N0 disease, and 33% had N+ disease. The 5-year RFS rates by category of
      quantified pathologic response were as follows: complete, 95%; near-complete,
      88%; major, 69%; and minor, 61% (P < .001). Major and minor response, high
      histologic grade, and perineural invasion were found to be significant predictors
      of decreased RFS on multivariate analysis. The 5-year RFS rates for patients with
      ypT3-4 or N+ disease were better for those with a near-complete response (94%)
      compared with those with a major (64%) or minor (61%) response (P < .02).
      Moderate to substantial agreement was observed between the 2 pathologists (kappa
      = 0.72). CONCLUSIONS: Quantified pathologic response is a predictor of RFS in
      patients with rectal adenocarcinoma and stratifies patients with high pathologic
      stage disease.

PMID- 24089345
TI  - [The molecular bypass: an established method for revascularisation of non
      operable PAD patients or merely a future vision].
AB  - Collateral vessel growth is a physiological process that is not equally
      pronounced in all people. After the development of a haemodynamically relevant
      stenosis in vascular systems, blood flow is directed through a collateral
      circulation to supply ischaemic tissue. This collateral circulation exists on the
      capillary level and by definition, is not composed of real new vessels. Postnatal
      vasculogenesis (true neovascularisation) occurs in the adult organism in tumour
      vascularisation, wound healing, in the endometrium, and in the context of chronic
      diseases such as rheumatoid arthritis and psoriasis. Reopening of the occluded
      vessel or use of artificial bypass grafts are the most attractive therapeutic
      approaches for treating peripheral arterial and coronary artery disease. These
      strategies have been exhausted in many patients; therefore augmentation of
      arteriogenesis can be more useful. Arteriogenesis, the promotion of natural
      collateral growth, is a hot topic in vascular research. Monocytes play a key role
      in arteriogenesis by "homing" to areas of collateral vessel growth and locally
      secrete multiple essential growth factors. Furthermore, stem cells of different
      origins, endothelial progenitor cells or mononuclear cells are currently being
      used to promote vessel growth. Also, the application of growth factors such as
      VEGF, MCP-1, GM-CSF have been already used in clinical trials. This review
      article describes the physiology and pathophysiology of vascular stenoses and
      their compensation mechanisms. The review also gives an overview of current
      treatment approaches and new strategies for non-operable PAD patients. The
      article presents the current cell and growth factor-related studies, as well as
      results of balloon dilatation and stent implantation or bypass surgery studies
      for improvement of revascularisation. 

PMID- 24089346
TI  - Materials research at Fudan University.

PMID- 24089348
TI  - Visual-size molecular recognition based on gels.
AB  - Since their discovery, stimuli-responsive organogels have garnered considerable
      and increasing attention from a broad range of research fields. In consideration
      of an one-dimensional ordered relay in anisotropic phase, the assembled gel
      networks can amplify various properties of the functional moieties possessed by
      the gelator molecules. Recently, substantial efforts have been focused on the
      development of facile, straightforward, and low-cost molecular recognition
      approaches by using nanostructured gel matrices as visual sensing platforms. In
      this research news, the recent progresses in macroscopic or visual-size molecular
      recognition for a number of homologues, isomers, and anions, as well as extremely
      challenging chiral enantiomers, using polymer and molecular gels are reviewed.
      Several strategies--including guest molecular competition, hydrogen-bonding
      blocking, and metal-coordination--for visual discrimination are included.
      Finally, the future trends and potential application in facile visual-size
      molecular recognition based on organogel matrices are highlighted.

PMID- 24089349
TI  - Amorphous photonic crystals with only short-range order.
AB  - Distinct from conventional photonic crystals with both short- and long-range
      order, amorphous photonic crystals that possess only short-range order show
      interesting optical responses owing to their unique structural features.
      Amorphous photonic crystals exhibit unique light scattering and transport, which
      lead to a variety of interesting phenomena such as isotropic photonic bandgaps or
      pseudogaps, noniridescent structural colors, and light localization. Recent
      experimental and theoretical advances in the study of amorphous photonic crystals
      are summarized, focusing on their unique optical properties, artificial
      fabrication, bionspiration, and potential applications. 

PMID- 24089350
TI  - Low-dimensional nanostructure ultraviolet photodetectors.
AB  - Low-dimensional (LD) nanostructures are ideal systems for constructing high
      performance photodetectors due to their tailored geometries, high surface-area-to
      volume ratios and rationally designed surfaces. This article provides a brief
      summary about recent progress on LD nanostructures based visible-light-blind
      ultraviolet photodetectors. The current challenges and an outlook on the future
      developments of this research field are summarized and highlighted. 

PMID- 24089351
TI  - ZnO nanoparticles applied to bioimaging and drug delivery.
AB  - The last decade has seen significant achievements in biomedical diagnosis and
      therapy at the levels of cells and molecules. Nanoparticles with luminescent or
      magnetic properties are used as detection probes and drug carriers, both in vitro
      and in vivo. ZnO nanoparticles, due to their good biocompatibility and low cost,
      have shown promising potential in bioimaging and drug delivery. The recent
      exciting progress on the biomedical applications of ZnO-based nanomaterials is
      reviewed here, along with discussions on the advantages and limitations of these
      advanced materials and suggestions for improving methods. 

PMID- 24089352
TI  - Recent progress in supercapacitors: from materials design to system construction.
AB  - Supercapacitors are currently attracting intensive attention because they can
      provide energy density by orders of magnitude higher than dielectric capacitors,
      greater power density, and longer cycling ability than batteries. The main
      challenge for supercapacitors is to develop them with high energy density that is
      close to that of a current rechargeable battery, while maintaining their inherent
      characteristics of high power and long cycling life. Consequently, much research
      has been devoted to enhance the performance of supercapacitors by either
      maximizing the specific capacitance and/or increasing the cell voltage. The
      latest advances in the exploration and development of new supercapacitor systems
      and related electrode materials are highlighted. Also, the prospects and
      challenges in practical application are analyzed, aiming to give deep insights
      into the material science and electrochemical fields. 

PMID- 24089353
TI  - Recent advances in applications and performance of inorganic hollow spheres in
      devices.
AB  - Inorganic hollow spheres have wide, important applications due to their unique
      structure, controllable morphology, and composition. Recent developments in the
      application and performance of inorganic hollow spheres in solar cells, UV
      photodectors, gas sensors, and supercapacitors are discussed. For each inorganic
      hollow sphere based device, a critical comment is given based on knowledge and
      related research experience. Some perspectives on the future research and
      development of these inorganic-hollow-sphere devices are given. 

PMID- 24089354
TI  - Superhydrophobic graphene-based materials: surface construction and functional
      applications.
AB  - Many naturally occurring surfaces have superhydrophobicity that fulfils their
      functional demands, which has inspired considerable interest to develop similar
      artificial superhydrophobic surfaces with a variety of functionalities. Graphene
      is an ideal candidate for functional superhydrophobic surfaces due to its
      exceptional physicochemical properties. The recent advances in this emerging
      field are summarized, including the wetting behavior of water on graphene and the
      formation of crumpling/nanoparticle/foam-induced hierarchical structures, with
      emphasis on fundamental understanding for related processes. The potential
      applications in energy, environmental remediation, and thermal management are
      also discussed. 

PMID- 24089355
TI  - Resistin derived from diabetic perivascular adipose tissue up-regulates vascular
      expression of osteopontin via the AP-1 signalling pathway.
AB  - Perivascular adipose tissue (PVAT) is implicated in the development of vascular
      diseases; however, the roles of PVAT on OPN expression in diabetic vasculature
      remain to be determined. This study investigated the role of adipokines derived
      from diabetic PVAT in regulating the vascular expression of OPN and explored the
      mechanisms involved. Aortic sections of ob/ob and high-fat diet (HFD)-induced
      obese (DIO) mice showed an increased expression of OPN, which was paralleled by
      increased amounts of PVAT characterized by enlargement of adipocytes. In the
      earlier phase of HFD feeding, macrophage infiltration was mainly localized to the
      area of PVAT at which adipocytes were enlarged, suggesting a potential link of
      activated adipocytes to macrophage infiltration. PVAT sections of ob/ob and DIO
      mice revealed a significantly greater number of macrophages with increased
      expression of adipokines, including resistin and visfatin. The distribution of
      resistin in PVAT mostly co-localized with macrophages, while visfatin was
      expressed in macrophages and other cells. In in vitro studies, OPN expression in
      vascular smooth muscle cells (VSMCs) co-cultured with PVAT of DIO mice was
      significantly increased, which was attenuated by a resistin-neutralizing
      antibody. Likewise, resistin up-regulated expression of OPN mRNA and protein in
      cultured VSMCs and the pivotal role of AP-1 in resistin-induced OPN transcription
      was demonstrated. Resistin produced by PVAT plays a pivotal role in the up
      regulated expression of OPN in the diabetic vasculature via a signalling pathway
      that involves activation of AP-1.

PMID- 24089357
TI  - Potential utility of cell sheets derived from the anterior cruciate ligament and
      synovium fabricated in temperature-responsive culture dishes.
AB  - Development of tissue-engineered materials to treat anterior cruciate ligament
      (ACL) injury has been limited by the lack of phenotypic markers. We investigated
      the feasibility of inducing ACL regeneration using cell sheet technology based on
      the expression of tenomodulin (TNMD) as an early phenotypic marker of ligaments.
      ACL remnants, the synovium surrounding cruciate ligaments (SCL), the synovium
      surrounding the infrapatellar fat pads (SIF), and subcutaneous fat tissue (SCF)
      were obtained from patients undergoing ACL reconstruction or total knee
      arthroplasty. ACL cell sheets and SCL-derived cell sheets were fabricated
      successfully A three-dimensional bioengineered ACL was generated by combining
      triple-layered ACL cell sheets with a bioabsorbable mesh composite.
      Immunohistochemical examination showed that TNMD was expressed in human ACL
      fibers, triple-layered ACL cell sheets, ACL remnants, SCL, and SIF, but not in
      SCF. Real-time PCR showed that TNMD mRNA was expressed at substantially higher
      levels in the ACL, SCL, and SIF than in the SCF. These results suggest that TNMD
      is a specific marker of the human ACL and that ACL sheets have a phenotype
      similar to that of the ACL. The greater expression of TNMD in the SCL- and SIF-
      suggests that the synovium is a potential cell source for ACL regeneration.

PMID- 24089358
TI  - Shutdown!

PMID- 24089359
TI  - Piezoelectric tuning fork probe for atomic force microscopy imaging and specific
      recognition force spectroscopy of an enzyme and its ligand.
AB  - Piezoelectric quartz tuning fork has drawn the attention of many researchers for
      the development of new atomic force microscopy (AFM) self-sensing probes.
      However, only few works have been done for soft biological materials imaging in
      air or aqueous conditions. The aim of this work was to demonstrate the efficiency
      of the AFM tuning fork probe to perform high-resolution imaging of proteins and
      to study the specific interaction between a ligand and its receptor in aqueous
      media. Thus, a new kind of self-sensing AFM sensor was introduced to realize
      imaging and biochemical specific recognition spectroscopy of glucose oxidase
      enzyme using a new chemical functionalization procedure of the metallic tips
      based on the electrochemical reduction of diazonium salt. This scanning probe as
      well as the functionalization strategy proved to be efficient respectively for
      the topography and force spectroscopy of soft biological materials in buffer
      conditions.

PMID- 24089360
TI  - Grb7 and Filamin-a associate and are colocalized to cell membrane ruffles upon
      EGF stimulation.
AB  - Grb7 is an adaptor molecule mediating signal transduction from multiple cell
      surface receptors to diverse downstream pathways. Grb7, along with Grb10 and
      Grb14, make up the Grb7 protein family. This protein family has been shown to be
      overexpressed in certain cancers and cancer cell lines. Grb7 and a receptor
      tyrosine kinase, ErbB2, are overexpressed in 20-30% of breast cancers. Grb7
      overexpression has been linked to enhanced cell migration and metastasis,
      although the participants in these pathways have not been fully determined. In
      this study, we report the Grb7 protein interacts with Filamin-a, an actin
      crosslinking component of the cell cytoskeleton. Additionally, we have
      demonstrated the interaction between Grb7 and Flna is specific to the RA-PH
      domains of Grb7, and the immunoglobulin-like repeat 16-19 domains of Flna. We
      demonstrate that full-length Grb7 and Flna interact in the mammalian cellular
      environment, as well as in vitro. Immunofluorescent microscopy shows potential co
      localization of Grb7 and Flna in membrane ruffles upon epidermal growth factor
      stimulation. These studies are amongst the first to establish a clear connection
      between Grb7 signaling and cytoskeletal remodeling.

PMID- 24089362
TI  - C-H...O hydrogen bonds in FK506-binding protein-ligand interactions.
AB  - Hydrogen bonds are important interaction forces observed in protein structures.
      They can be classified as stronger or weaker depending on their energy, thereby
      reflecting on the type of donor. The contribution of weak hydrogen bonds is
      deemed as an important factor toward structure stability along with the stronger
      bonds. One such bond, the C-H...O type hydrogen bond, is shown to make a
      contribution in maintaining three dimensional structures of proteins. Apart from
      their presence within protein structures, the role of these bonds in protein
      ligand interactions is also noteworthy. In this study, we present a statistical
      analysis on the presence of C-H...O hydrogen bonds observed between FKBPs and
      their cognate ligands. The FK506-binding proteins (FKBPs) carry peptidyl cis
      trans isomerase activity apart from the immunosuppressive property by binding to
      the immunosuppressive drugs FK506 or rapamycin. Because the active site of FKBPs
      is lined up by many hydrophobic residues, we speculated that the prevalence of C
      H...O hydrogen bonds will be considerable. In a total of 25 structures analyzed,
      a higher frequency of C-H...O hydrogen bonds is observed in comparison with the
      stronger hydrogen bonds. These C-H...O hydrogen bonds are dominated by a highly
      conserved donor, the C(alpha/beta) of Val55 and an acceptor, the backbone oxygen
      of Glu54. Both these residues are positioned in the beta4-alpha1 loop, whereas
      the other residues Tyr26, Phe36 and Phe99 with higher frequencies are lined up at
      the opposite face of the active site. These preferences could be implicated in
      FKBP pharmacophore models toward enhancing the ligand affinity. This study could
      be a prelude to studying other proteins with hydrophobic pockets to gain better
      insights into ligand recognition.

PMID- 24089361
TI  - Characterizing the S-layer structure and anti-S-layer antibody recognition on
      intact Tannerella forsythia cells by scanning probe microscopy and small angle X
      ray scattering.
AB  - Tannerella forsythia is among the most potent triggers of periodontal diseases,
      and approaches to understand underlying mechanisms are currently intensively
      pursued. A ~22-nm-thick, 2D crystalline surface (S-) layer that completely covers
      Tannerella forsythia cells is crucially involved in the bacterium-host cross
      talk. The S-layer is composed of two intercalating glycoproteins (TfsA-GP, TfsB
      GP) that are aligned into a periodic lattice. To characterize this unique S-layer
      structure at the nanometer scale directly on intact T. forsythia cells, three
      complementary methods, i.e., small-angle X-ray scattering (SAXS), atomic force
      microscopy (AFM), and single-molecular force spectroscopy (SMFS), were applied.
      SAXS served as a difference method using signals from wild-type and S-layer
      deficient cells for data evaluation, revealing two possible models for the
      assembly of the glycoproteins. Direct high-resolution imaging of the outer
      surface of T. forsythia wild-type cells by AFM revealed a p4 structure with a
      lattice constant of ~9.0 nm. In contrast, on mutant cells, no periodic lattice
      could be visualized. Additionally, SMFS was used to probe specific interaction
      forces between an anti-TfsA antibody coupled to the AFM tip and the S-layer as
      present on T. forsythia wild-type and mutant cells, displaying TfsA-GP alone.
      Unbinding forces between the antibody and wild-type cells were greater than with
      mutant cells. This indicated that the TfsA-GP is not so strongly attached to the
      mutant cell surface when the co-assembling TfsB-GP is missing. Altogether, the
      data gained from SAXS, AFM, and SMFS confirm the current model of the S-layer
      architecture with two intercalating S-layer glycoproteins and TfsA-GP being
      mainly outwardly oriented.

PMID- 24089363
TI  - Interaction investigations of HipA binding to HipB dimer and HipB dimer + DNA
      complex: a molecular dynamics simulation study.
AB  - We carried out molecular dynamics simulations and free energy calculations for a
      series of ternary and diplex models for the HipA protein, HipB dimer, and DNA
      molecule to address the mechanism of HipA sequestration and the binding order of
      events from apo HipB/HipA to 2HipA + HipB dimer + DNA complex. The results
      revealed that the combination of DNA with the HipB dimer is energetically
      favorable for the combination of HipB dimer with HipA protein. The binding of DNA
      to HipB dimer induces a long-range allosteric communication from the HipB2 -DNA
      interface to the HipA-HipB2 interface, which involves the closeness of alpha1
      helices of HipB dimer to HipA protein and formations of extra hydrogen bonds in
      the HipA-HipB2 interface through the extension of alpha2/3 helices in the HipB
      dimer. These simulated results suggested that the DNA molecule, as a regulative
      media, modulates the HipB dimer conformation, consequently increasing the
      interactions of HipB dimer with the HipA proteins, which explains the mechanism
      of HipA sequestration reported by the previous experiment. Simultaneously, these
      simulations also explored that the thermodynamic binding order in a simulated
      physiological environment, that is, the HipB dimer first bind to DNA to form HipB
      dimer + DNA complex, then capturing strongly the HipA proteins to form a ternary
      complex, 2HipA + HipB dimer + DNA, for sequestrating HipA in the nucleoid.

PMID- 24089364
TI  - Molecular recognition of a model globular protein apomyoglobin by synthetic
      receptor cyclodextrin: effect of fluorescence modification of the protein and
      cavity size of the receptor in the interaction.
AB  - Labelling of proteins with some extrinsic probe is unavoidable in molecular
      biology research. Particularly, spectroscopic studies in the optical region
      require fluorescence modification of native proteins by attaching polycyclic
      aromatic fluoroprobe with the proteins under investigation. Our present study
      aims to address the consequence of the attachment of a fluoroprobe at the protein
      surface in the molecular recognition of the protein by selectively small model
      receptor. A spectroscopic study involving apomyoglobin (Apo-Mb) and cyclodextrin
      (CyD) of various cavity sizes as model globular protein and synthetic receptors,
      respectively, using steady-state and picosecond-resolved techniques, is detailed
      here. A study involving Forster resonance energy transfer, between intrinsic
      amino acid tryptophan (donor) and N, N-dimethyl naphthalene moiety of the
      extrinsic dansyl probes at the surface of Apo-Mb, precisely monitor changes in
      donor acceptor distance as a consequence of interaction of the protein with CyD
      having different cavity sizes (beta and gamma variety). Molecular modelling
      studies on the interaction of tryptophan and dansyl probe with beta-CyD is
      reported here and found to be consistent with the experimental observations. In
      order to investigate structural aspects of the interacting protein, we have used
      circular dichroism spectroscopy. Temperature-dependent circular dichroism studies
      explore the change in the secondary structure of Apo-Mb in association with CyD,
      before and after fluorescence modification of the protein. Overall, the study
      well exemplifies approaches to protein recognition by CyD as a synthetic receptor
      and offers a cautionary note on the use of hydrophobic fluorescent labels for
      proteins in biochemical studies involving recognition of molecules.

PMID- 24089365
TI  - Investigating differential cell-matrix adhesion by directly comparative single
      cell force spectroscopy.
AB  - Tissue-embedded cells are often exposed to a complex mixture of extracellular
      matrix (ECM) molecules, to which they bind with different cell adhesion receptors
      and affinities. Differential cell adhesion to ECM components is believed to
      regulate many aspects of tissue function, such as the sorting of specific cell
      types into different tissue compartments or ECM niches. In turn, aberrant
      switches in cell adhesion preferences may contribute to cell misplacement, tissue
      invasion, and metastasis. Methods to determine differential adhesion profiles of
      single cells are therefore desirable, but established bulk assays usually only
      test cell population adhesion to a single type of ECM molecule. We have recently
      demonstrated that atomic force microscopy-based single-cell force spectroscopy
      (SCFS), performed on bifunctional, microstructured adhesion substrates, provides
      a useful tool for accurately quantitating differential matrix adhesion of single
      Chinese hamster ovary cells to laminin and collagen I. Here, we have extended
      this approach to include additional ECM substrates, such as bifunctional collagen
      I/collagen IV surfaces, as well as adhesion-passivated control surfaces. We
      investigate differential single cell adhesion to these substrates and analyze in
      detail suitable experimental conditions for comparative SCFS, including optimal
      cell-substrate contact times and the impact of force cycle repetitions on single
      cell adhesion force statistics. Insight gained through these experiments may help
      in adapting this technique to other ECM molecules and cell systems, making
      directly comparative SCFS a versatile tool for comparing receptor-mediated cell
      adhesion to different matrix molecules in a wide range of biological contexts.

PMID- 24089366
TI  - Combination of fluorescence microscopy and nanomotion detection to characterize
      bacteria.
AB  - Antibiotic-resistant pathogens are a major health concern in everyday clinical
      practice. Because their detection by conventional microbial techniques requires
      minimally 24 h, some of us have recently introduced a nanomechanical sensor,
      which can reveal motion at the nanoscale. By monitoring the fluctuations of the
      sensor, this technique can evidence the presence of bacteria and their
      susceptibility to antibiotics in less than 1 h. Their amplitude correlates to the
      metabolism of the bacteria and is a powerful tool to characterize these
      microorganisms at low densities. This technique is new and calls for an effort to
      optimize its protocol and determine its limits. Indeed, many questions remain
      unanswered, such as the detection limits or the correlation between the bacterial
      distribution on the sensor and the detection's output. In this work, we couple
      fluorescence microscopy to the nanomotion investigation to determine the optimal
      experimental protocols and to highlight the effect of the different bacterial
      distributions on the sensor.

PMID- 24089367
TI  - Conformational dynamics of individual antibodies using computational docking and
      AFM.
AB  - Molecular recognition between a receptor and a ligand requires a certain level of
      flexibility in macromolecules. In this study, we aimed at analyzing the
      conformational variability of receptors portrayed by monoclonal antibodies that
      have been individually imaged using atomic force microscopy (AFM). Individual
      antibodies were chemically coupled to activated mica surface, and they have been
      imaged using AFM in ambient conditions. The resulting topographical surface of
      antibodies was used to assemble the three subunits constituting antibodies: two
      antigen-binding fragments and one crystallizable fragment using a surface
      constrained computational docking approach. Reconstructed structures based on 10
      individual topographical surfaces of antibodies are presented for which
      separation and relative orientation of the subunits were measured. When compared
      with three X-ray structures of antibodies present in the protein data bank
      database, results indicate that several arrangements of the reconstructed
      subunits are comparable with those of known structures. Nevertheless, no
      reconstructed structure superimposes adequately to any particular X-ray structure
      consequence of the antibody flexibility. We conclude that high-resolution AFM
      imaging with appropriate computational reconstruction tools is adapted to study
      the conformational dynamics of large individual macromolecules deposited on mica.

PMID- 24089369
TI  - Increased coherence of white matter fiber tract organization in adults with
      Asperger syndrome: a diffusion tensor imaging study.
AB  - To investigate whether there are global white matter (WM) differences between
      autistic and healthy adults, we performed diffusion tensor imaging (DTI) in 14
      male adults with Asperger syndrome (AS) and 19 gender-, age-, and intelligence
      quotient-matched controls. We focused on individuals with high-functioning autism
      spectrum disorder (ASD), AS, to decrease heterogeneity caused by large variation
      in the cognitive profile. Previous DTI studies of ASD have mainly focused on
      finding local changes in fractional anisotropy (FA) and mean diffusivity (MD),
      two indexes used to characterize microstructural properties of WM. Although the
      local or voxel-based approaches may be able to provide detailed information in
      terms of location of the observed differences, such results are known to be
      highly sensitive to partial volume effects, registration errors, or placement of
      the regions of interest. Therefore, we performed global histogram analyses of (a)
      whole-brain tractography results and (b) skeletonized WM masks. In addition to
      the FA and MD, the planar diffusion coefficient (CP) was computed as it can
      provide more specific information of the complexity of the neural structure. Our
      main finding indicated that adults with AS had higher mean FA values than
      controls. A less complex neural structure in adults with AS could have explained
      the results, but no significant difference in CP was found. Our results suggest
      that there are global abnormalities in the WM tissue of adults with AS.

PMID- 24089370
TI  - Prenatal hypoxia programs changes in beta-adrenergic signaling and postnatal
      cardiac contractile dysfunction.
AB  - Prenatal hypoxia leads to an increased risk of adult cardiovascular disease. We
      have previously demonstrated a programming effect of prenatal hypoxia on the
      cardiac beta-adrenergic (betaAR) response. The aim of this study was to determine
      1) whether the decrease in betaAR sensitivity in prenatally hypoxic 5-wk old
      chicken hearts is linked to changes in beta1AR/beta2ARs, Galphai expression and
      cAMP accumulation and 2) whether prenatal hypoxia has an effect on heart function
      in vivo. We incubated eggs in normoxia (N, 21% O2) or hypoxia from day 0 (H, 14%
      O2) and raised the posthatchlings to 5 wk of age. Cardiac beta1AR/beta2ARs were
      assessed through competitive binding of [(3)H]CGP-12177 with specific beta1AR or
      beta2AR blockers. Galphas and Galphai proteins were assessed by Western blot and
      cAMP accumulation by ELISA. Echocardiograms were recorded in anesthetized birds
      to evaluate diastolic/systolic diameter and heart rate and tissue sections were
      stained for collagen. We found an increase in relative heart mass, beta1ARs, and
      Galphas in prenatally hypoxic hearts. cAMP levels after isoproterenol stimulation
      and collagen content was not changed in H compared with N, but in vivo
      echocardiograms showed systolic contractile dysfunction. The changes in betaAR
      and G protein subtypes may be indicative of an early compensatory stage in the
      progression of cardiac dysfunction, further supported by the cardiac hypertrophy
      and systolic contractile dysfunction. We suggest that it is not the changes in
      the proximal part of the betaAR system that causes the decreased cardiac
      contractility, but Ca(2+) handling mechanisms further downstream in the betaAR
      signaling cascade.

PMID- 24089371
TI  - Fetal iron deficiency alters the proteome of adult rat hippocampal synaptosomes.
AB  - Fetal and neonatal iron deficiency results in cognitive impairments in adulthood
      despite prompt postnatal iron replenishment. To systematically determine whether
      abnormal expression and localization of proteins that regulate adult synaptic
      efficacy are involved, we used a quantitative proteomic approach (isobaric tags
      for relative and absolute quantitation, iTRAQ) and pathway analysis to identify
      dysregulated proteins in hippocampal synapses of fetal iron deficiency model. Rat
      pups were made iron deficient (ID) from gestational day 2 through postnatal day
      (P) 7 by providing pregnant and nursing dams an ID diet (4 ppm Fe) after which
      they were rescued with an iron-sufficient diet (200 ppm Fe). This paradigm
      resulted in a 40% loss of brain iron at P15 with complete recovery by P56.
      Synaptosomes were prepared from hippocampi of the formerly iron-deficient (FID)
      and always iron-sufficient controls rats at P65 using a sucrose gradient method.
      Six replicates per group that underwent iTRAQ labeling and LC-MS/MS analysis for
      protein identification and comparison elucidated 331 differentially expressed
      proteins. Western analysis was used to confirm findings for selected proteins in
      the glutamate receptor signaling pathway, which regulates hippocampal synaptic
      plasticity, a cellular process critical for learning and memory. Bioinformatics
      were performed using knowledge-based Interactive Pathway Analysis. FID
      synaptosomes show altered expression of synaptic proteins-mediated cellular
      signalings, supporting persistent impacts of fetal iron deficiency on synaptic
      efficacy, which likely cause the cognitive dysfunction and neurobehavioral
      abnormalities. Importantly, the findings uncover previously unsuspected pathways,
      including neuronal nitric oxide synthase signaling, identifying additional
      mechanisms that may contribute to the long-term biobehavioral deficits. 

PMID- 24089373
TI  - Influence of abnormally high leptin levels during pregnancy on metabolic
      phenotypes in progeny mice.
AB  - Maternal obesity increases the risk of obesity in offspring, and obesity is
      accompanied by an increase in blood leptin levels. The "yellow" mutation at the
      mouse agouti locus (A(y)) increases blood leptin levels in C57BL preobese
      pregnant mice without affecting other metabolic characteristics. We investigated
      the influence of the A(y) mutation or leptin injection at the end of pregnancy in
      C57BL mice on metabolic phenotypes and the susceptibility to diet-induced obesity
      (DIO) in offspring. In both C57BL-A(y) and leptin-treated mice, the maternal
      effect was more pronounced in male offspring. Compared with males born to control
      mothers, males born to A(y) mothers displayed equal food intake (FI) but
      decreased body weight (BW) gain after weaning, equal glucose tolerance, and
      enhanced FI-to-BW ratios on the standard diet but the same FI and BW on the high
      fat diet. Males born to A(y) mothers were less responsive to the anorectic effect
      of exogenous leptin and less resistant to fasting (were not hyperphagic and
      gained less weight during refeeding after food deprivation) compared with males
      born to control mothers. However, all progeny displayed equal hypothalamic
      expression of Agouti gene-related protein (AgRP), neuropeptide Y (NPY), and
      proopiomelanocortin (POMC) and equal plasma leptin and glucose levels after food
      deprivation. Leptin injections in C57BL mice on day 17 of pregnancy decreased BW
      in both male and female offspring but inhibited FI and DIO only in male
      offspring. Our results show that hyperleptinemia during pregnancy has sex
      specific long-term effects on energy balance regulation in progeny and does not
      predispose offspring to developing obesity. 

PMID- 24089374
TI  - Mas receptor deficiency is associated with worsening of lipid profile and severe
      hepatic steatosis in ApoE-knockout mice.
AB  - The classical renin-angiotensin system pathway has been recently updated with the
      identification of additional molecules [such as angiotensin converting enzyme 2,
      ANG-(1-7), and Mas receptor] that might improve some pathophysiological processes
      in chronic inflammatory diseases. In the present study, we focused on the
      potential protective role of Mas receptor activation on mouse lipid profile,
      liver steatosis, and atherogenesis. Mas/apolipoprotein E (ApoE)-double-knockout
      (DKO) mice (based on C57BL/6 strain of 20 wk of age) were fed under normal diet
      and compared with aged-matched Mas and ApoE-single-knockout (KO), as well as wild
      type mice. Mas/ApoE double deficiency was associated with increased serum levels
      of atherogenic fractions of cholesterol, triglycerides, and fasting glucose
      compared with wild-type or single KO. Serum levels of HDL or leptin in DKO were
      lower than in other groups. Hepatic lipid content as well as alanine
      aminotransferase serum levels were increased in DKO compared with wild-type or
      single-KO animals. Accordingly, the hepatic protein content of mediators related
      to atherosclerotic inflammation, such as peroxisome proliferator-activated
      receptor-alpha and liver X receptor, was altered in an adverse way in DKO
      compared with ApoE-KO. On the other hand, DKO mice did not display increased
      atherogenesis and intraplaque inflammation compared with ApoE-KO group. In
      conclusion, Mas deletion in ApoE-KO mice was associated with development of
      severe liver steatosis and dyslipidemia without affecting concomitant
      atherosclerosis. Mas receptor activation might represent promising strategies for
      future treatments targeting both hepatic and metabolic alterations in chronic
      conditions clustering these disorders. 

PMID- 24089372
TI  - Paradoxical effects of heme arginate on survival of myocutaneous flaps.
AB  - Ischemia reperfusion injury (IRI) contributes to partial flap and solid organ
      transplant failure. Heme-oxygenase 1 (HO-1) is an inducible, cytoprotective
      enzyme which protects against IRI in solid organ transplant models. Heme arginate
      (HA), a HO-1 inducer, is a promising, translatable, preconditioning agent. This
      study investigated the effects of preconditioning with HA on the clinical outcome
      of a myocutaneous IRI model. Forty male Lewis rats were randomized to
      intravenously receive 1) Control-NaCl, 2) HA, 3) HA and tin mesoporphyrin (SnMP),
      a HO-1 inhibitor; and 4) SnMP alone. Twenty-four hours later, an in situ
      transverse rectus abdominis myocutaneous flap was performed under isoflurane
      anesthesia. Viability of flaps was measured clinically and by laser-Doppler
      perfusion scanning. In vitro work on human epidermal keratinocytes (HEKa)
      assessed the effects of HA, SnMP, and the iron chelator desferrioxamine on 1)
      cytotoxicity, 2) intracellular reactive oxygen species (ROS) concentration, and
      3) ROS-mediated DNA damage. In contrast to our hypothesis, HA preconditioning
      produced over 30% more flap necrosis at 48 h compared with controls (P = 0.02).
      HA-containing treatments produced significantly worse flap perfusion at all
      postoperative time points. In vitro work showed that HA is cytotoxic to
      keratinocytes. This cytotoxicity was independent of HO-1 and was mediated by the
      generation of ROS by free heme. In contrast to solid organ data, pharmacological
      preconditioning with HA significantly worsened clinical outcome, thus indicating
      that this is not a viable approach in free flap research. 

PMID- 24089375
TI  - Paraventricular nucleus control of blood pressure in two-kidney, one-clip rats:
      effects of exercise training and resting blood pressure.
AB  - Exercise-induced changes in gamma-aminobutyric acid (GABA) or nitric oxide
      signaling within the paraventricular nucleus (PVN) have not been studied in
      renovascular hypertension. We tested whether exercise training decreases mean
      arterial pressure (MAP) and renal sympathetic nerve activity (RSNA) in two
      kidney, one-clip (2K-1C) hypertensive rats due to enhanced nitric oxide or GABA
      signaling within PVN. Conscious, unrestrained male Sprague-Dawley rats with
      either sham (Sham) or right renal artery clipping (2K-1C) were assigned to
      sedentary (SED) or voluntary wheel running (ExT) for 6 or 12 wk. MAP and
      angiotensin II (ANG II) were elevated in 2K-1C SED rats. The 2K-1C ExT rats
      displayed lower MAP at 6 wk that did not decline further by 12 wk. Plasma ANG II
      was lower in 2K-1C ExT rats. Increases in MAP, heart rate, and RSNA to blockade
      of PVN nitric oxide in 2K-1C SED rats were attenuated compared with either Sham
      group. Exercise training restored the responses in 2K-1C ExT rats. The increase
      in MAP in response to bicuculline was inversely correlated with baseline MAP. The
      rise in MAP was lower in 2K-1C SED vs. either Sham group and was normalized in
      the 2K-1C ExT rats. Paradoxically, heart rate and RSNA responses were not
      diminished in 2K-1C SED rats but were significantly lower in the 2K-1C ExT rats.
      Thus the decrease in arterial pressure in 2K-1C hypertension associated with
      exercise training is likely due to diminished excitatory inputs to PVN because of
      lower ANG II and higher nitritergic tone rather than enhanced GABA inhibition of
      sympathetic output. 

PMID- 24089376
TI  - Synergistic effects of C-peptide and insulin on low O2-induced ATP release from
      human erythrocytes.
AB  - Erythrocytes participate in the matching of oxygen (O2) delivery with local need
      in skeletal muscle via the release of O2 and the vasodilator, ATP. It was
      reported that a concentration of insulin found in humans with insulin resistance
      inhibits low O2-induced ATP release. However, in vivo, insulin is coreleased with
      connecting peptide (C-peptide) at equimolar concentrations, but because of the
      shorter insulin half-life, the peptides circulate at ratios of C-peptide to
      insulin ranging from 1:1 to 6:1. Here, we investigate the hypothesis that C
      peptide and insulin work synergistically to maintain low O2-induced ATP release
      from human erythrocytes. Using a thin-film tonometer to alter O2 tension, we
      determined that either C-peptide or insulin alone inhibits low O2-induced ATP
      release in a concentration-dependent manner; however, coadministration of the
      peptides at a 1:1 ratio does not (n = 5; P < 0.05). Because this ratio of C
      peptide to insulin is not present in vivo for extended periods, we also
      investigated the effect of additional physiological ratios on ATP release. In the
      presence of insulin concentrations that would be found in fasting humans (0.05
      nM), C-peptide to insulin ratios of 4:1 and 6:1 did not adversely affect low O2
      induced ATP release. However, at a concentration of insulin found in the
      peripheral circulation of humans under postprandial conditions (0.5 nM), a ratio
      of C-peptide to insulin of 6:1 inhibited low O2-induced ATP release (n = 5).
      These findings demonstrate a heretofore unrecognized synergism between C-peptide
      and insulin that could have physiological importance in the regulation of
      perfusion distribution in skeletal muscle. 

PMID- 24089377
TI  - Beetroot juice supplementation speeds O2 uptake kinetics and improves exercise
      tolerance during severe-intensity exercise initiated from an elevated metabolic
      rate.
AB  - Recent research has suggested that dietary nitrate (NO3(-)) supplementation might
      alter the physiological responses to exercise via specific effects on type II
      muscle. Severe-intensity exercise initiated from an elevated metabolic rate would
      be expected to enhance the proportional activation of higher-order (type II)
      muscle fibers. The purpose of this study was, therefore, to test the hypothesis
      that, compared with placebo (PL), NO3(-)-rich beetroot juice (BR) supplementation
      would speed the phase II VO2 kinetics (tau(p)) and enhance exercise tolerance
      during severe-intensity exercise initiated from a baseline of moderate-intensity
      exercise. Nine healthy, physically active subjects were assigned in a randomized,
      double-blind, crossover design to receive BR (140 ml/day, containing ~8 mmol of
      NO3(-)) and PL (140 ml/day, containing ~0.003 mmol of NO3(-)) for 6 days. On days
      4, 5, and 6 of the supplementation periods, subjects completed a double-step
      exercise protocol that included transitions from unloaded to moderate-intensity
      exercise (U->M) followed immediately by moderate to severe-intensity exercise (M
      >S). Compared with PL, BR elevated resting plasma nitrite concentration (PL: 65
      +/- 32 vs. BR: 348 +/- 170 nM, P < 0.01) and reduced the VO2 tau(p) in M->S (PL:
      46 +/- 13 vs. BR: 36 +/- 10 s, P < 0.05) but not U->M (PL: 25 +/- 4 vs. BR: 27 +/
      6 s, P > 0.05). During M->S exercise, the faster VO2 kinetics coincided with
      faster near-infrared spectroscopy-derived muscle [deoxyhemoglobin] kinetics (tau;
      PL: 20 +/- 9 vs. BR: 10 +/- 3 s, P < 0.05) and a 22% greater time-to-task failure
      (PL: 521 +/- 158 vs. BR: 635 +/- 258 s, P < 0.05). Dietary supplementation with
      NO3(-)-rich BR juice speeds VO2 kinetics and enhances exercise tolerance during
      severe-intensity exercise when initiated from an elevated metabolic rate.

PMID- 24089378
TI  - Role of ceruloplasmin in nitric oxide metabolism in plasma of humans and sheep: a
      comparison of adults and fetuses.
AB  - Nitric oxide (NO) is metabolized in plasma, in part by the ferroxidase
      ceruloplasmin (Cp), to form nitrite and nitrosothiols (SNOs), which are proposed
      to mediate protective responses to hypoxia and ischemia. We hypothesized that NO
      metabolism would be attenuated in fetal plasma due to low Cp activity. We
      measured Cp concentrations and activity in plasma samples collected from adults
      and fetuses of humans and sheep. We then added NO ([NO]: 1.5 or 100 MUM) to
      plasma and aqueous buffer and measured rates of NO disappearance and the
      production of nitrite and SNO. Cp concentrations in fetal plasma were <15% of
      adult levels. In aqueous buffer, 1.5 MUM NO disappeared with a half-life of 347
      +/- 64 s (means +/- SE) but in plasma of humans the half-life was 19 +/- 2 s
      (adult) and 11 +/- 1 s (fetus, P = 0.004) and in sheep it was 31 +/- 3 s (adult)
      and 43 +/- 5 s (fetus, P = 0.04). Cp activity was not correlated with the overall
      elimination half-life of NO or with the amount of SNO ([NO]: 100 MUM) or nitrite
      ([NO]: 1.5 or 100 MUM) produced but correlated with SNO yields at 1.5 MUM [NO] (r
      = 0.92, P = 0.04). Our data demonstrate that Cp is not essential to the increased
      rate of metabolism of NO in plasma relative to aqueous buffers and that it is not
      essential to the production of nitrite from NO. Cp may be involved in the
      conversion of NO to SNO in plasma under near-physiological concentrations of NO. 

PMID- 24089380
TI  - Roles of the circulating renin-angiotensin-aldosterone system in human pregnancy.
AB  - This review describes the changes that occur in circulating renin-angiotensin
      aldosterone system (RAAS) components in human pregnancy. These changes depend on
      endocrine secretions from the ovary and possibly the placenta and decidua. Not
      only do these hormonal secretions directly contribute to the increase in RAAS
      levels, they also cause physiological changes within the cardiovascular system
      and the kidney, which, in turn, induce reflex release of renal renin. High levels
      of ANG II play a critical role in maintaining circulating blood volume, blood
      pressure, and uteroplacental blood flow through interactions with the ANG II type
      I receptor and through increased production of downstream peptides acting on a
      changing ANG receptor phenotype. The increase in ANG II early in gestation is
      driven by estrogen-induced increments in angiotensinogen (AGT) levels, so there
      cannot be negative feedback leading to reduced ANG II production. AGT can exist
      in various forms in terms of redox state or complexed with other proteins as
      polymers; these affect the ability of renin to cleave ANG I from AGT. Thus,
      during pregnancy the rate of ANG I production varies not only because levels of
      renin change in response to homeostatic demand but also because AGT changes not
      only in concentration but in form. Activation of the circulating and intrarenal
      RAASs is essential for normal pregnancy outcome subserving the increased demand
      for salt and, hence, water during pregnancy. Thus, the complex integration of the
      secretions and actions of the circulating maternal renin-angiotensin system in
      pregnancy plays a key role in pregnancy outcome. 

PMID- 24089379
TI  - Human inflammatory and resolving lipid mediator responses to resistance exercise
      and ibuprofen treatment.
AB  - Classical proinflammatory eicosanoids, and more recently discovered lipid
      mediators with anti-inflammatory and proresolving bioactivity, exert a complex
      role in the initiation, control, and resolution of inflammation. Using a targeted
      lipidomics approach, we investigated circulating lipid mediator responses to
      resistance exercise and treatment with the NSAID ibuprofen. Human subjects
      undertook a single bout of unaccustomed resistance exercise (80% of one
      repetition maximum) following oral ingestion of ibuprofen (400 mg) or placebo
      control. Venous blood was collected during early recovery (0-3 h and 24 h
      postexercise), and serum lipid mediator composition was analyzed by LC-MS-based
      targeted lipidomics. Postexercise recovery was characterized by elevated levels
      of cyclooxygenase (COX)-1 and 2-derived prostanoids (TXB2, PGE2, PGD2, PGF2alpha,
      and PGI2), lipooxygenase (5-LOX, 12-LOX, and 15-LOX)-derived
      hydroxyeicosatetraenoic acids (HETEs), and leukotrienes (e.g., LTB4), and
      epoxygenase (CYP)-derived epoxy/dihydroxy eicosatrienoic acids
      (EpETrEs/DiHETrEs). Additionally, we detected elevated levels of bioactive lipid
      mediators with anti-inflammatory and proresolving properties, including
      arachidonic acid-derived lipoxins (LXA4 and LXB4), and the EPA (E-series) and DHA
      (D-series)-derived resolvins (RvD1 and RvE1), and protectins (PD1 isomer 10S, 17S
      diHDoHE). Ibuprofen treatment blocked exercise-induced increases in COX-1 and COX
      2-derived prostanoids but also resulted in off-target reductions in leukotriene
      biosynthesis, and a diminished proresolving lipid mediator response. CYP pathway
      product metabolism was also altered by ibuprofen treatment, as indicated by
      elevated postexercise serum 5,6-DiHETrE and 8,9-DiHETrE only in those receiving
      ibuprofen. These findings characterize the blood inflammatory lipid mediator
      response to unaccustomed resistance exercise in humans and show that acute
      proinflammatory signals are mechanistically linked to the induction of a
      biological active inflammatory resolution program, regulated by proresolving
      lipid mediators during postexercise recovery. 

PMID- 24089381
TI  - Sudden decrease in physical activity evokes adipocyte hyperplasia in 70- to 77
      day-old rats but not 49- to 56-day-old rats.
AB  - The cessation of physical activity in rodents and humans initiates obesogenic
      mechanisms. The overall purpose of the current study was to determine how the
      cessation of daily physical activity in rats at 49-56 days of age and at 70-77
      days of age via wheel lock (WL) affects adipose tissue characteristics. Male
      Wistar rats began voluntary running at 28 days old and were either killed at 49
      56 days old or at 70-77 days old. Two cohorts of rats always had wheel access
      (RUN), a second two cohorts of rats had wheel access restricted during the last 7
      days (7d-WL), and a third two cohorts of rats did not have access to a voluntary
      running wheel after the first 6 days of (SED). We observed more robust changes
      with WL in the 70- to 77-day-old rats. Compared with RUN rats, 7d-WL rats
      exhibited greater rates of gain in fat mass and percent body fat, increased
      adipocyte number, higher percentage of small adipocytes, and greater cyclin A1
      mRNA in epididymal and perirenal adipose tissue. In contrast, 49- to 56-day-old
      rats had no change in most of the same characteristics. There was no increase in
      inflammatory mRNA expression in either cohort with WL. These findings suggest
      that adipose tissue in 70- to 77-day-old rats is more protected from WL than 49-
      to 56-day-old rats and responds by expansion via hyperplasia. 

PMID- 24089382
TI  - High-saturated fat-sucrose feeding affects lactation energetics in control mice
      and mice selectively bred for high wheel-running behavior.
AB  - Feeding a diet high in fat and sucrose (HFS) during pregnancy and lactation is
      known to increase susceptibility to develop metabolic derangements later in life.
      A trait for increased behavioral activity may oppose these effects, since this
      would drain energy from milk produced to be made available to the offspring. To
      investigate these interactions, we assessed several components of behavioral
      energetics during lactation in control mice (C) and in mice of two lines
      selectively bred for high wheel-running activity (S1, S2) subjected to a HFS diet
      or a low-fat (LF) diet. Energy intake, litter growth, and milk energy output at
      peak lactation (MEO; assessed by subtracting maternal metabolic rate from energy
      intake) were elevated in HFS-feeding dams across all lines compared with the LF
      condition, an effect that was particularly evident in the S dams. This effect was
      not preceded by improved lactation behaviors assessed between postnatal days 1
      and 7 (PND 1-7). In fact, S1 dams had less high-quality nursing, and S2 dams
      showed poorer pup retrieval than C dams during PND 1-7, and S dams had generally
      higher levels of physical activity at peak lactation. These data demonstrate that
      HFS feeding increases MEO underlying increased litter and pup growth,
      particularly in mice with a trait for increased behavioral physical activity. 

PMID- 24089384
TI  - HRT risks outweigh benefits for chronic disease prevention, research confirms.

PMID- 24089383
TI  - Role of the locus coeruleus in enhanced orexin A-induced spontaneous physical
      activity in obesity-resistant rats.
AB  - Orexin/hypocretin terminals innervate noradrenergic locus coeruleus (LC) neurons
      that project to the prefrontral cortex, which may influence spontaneous physical
      activity (SPA) and energy balance. Obesity-resistant (OR) rats have higher orexin
      receptors (OXR) mRNA in the LC and other brain regions, as well as lower
      adiposity compared with obese rats. These findings led us to hypothesize that
      orexin activity in the LC is relevant for the OR phenotype. We compared OR rats
      to Sprague-Dawley rats. We predicted that: 1) brain OXR expression pattern is
      sufficient to differentiate OR from non-bred Sprague-Dawley rats; 2) nonresting
      energy expenditure (NREE) and orexin A (OXA)-stimulated SPA after injection in LC
      would be greater in OR rats; and 3) the effect of OXA on SPA would be greater
      than its effect on feeding. OXR mRNA from 11 brain sites and the SPA and feeding
      responses to OXA in the LC were determined. Body composition, basal SPA, and EE
      were determined. Principal component analysis of the OXR expression pattern
      differentiates OR and Sprague-Dawley rats and suggests the OXR mRNA in the LC is
      important in defining the OR phenotype. Compared with Sprague-Dawley rats, OR
      rats had greater SPA and NREE and lower resting EE and adiposity. SPA
      responsivity to OXA in the LC was greater in OR rats compared with Sprague-Dawley
      rats. OXA in the LC did not stimulate feeding in OR or Sprague-Dawley rats. These
      data suggest that the LC is a prominent site modulating OXA-stimulated SPA, which
      promotes lower adiposity and higher nonresting EE. 

PMID- 24089385
TI  - NINDS epilepsy and autism spectrum disorders workshop report.
AB  - The association of epilepsy and autism spectrum disorders (ASD), although well
      recognized, is poorly understood. The purpose of this report is to summarize the
      discussion of a workshop sponsored by the National Institute of Neurological
      Disorders and Stroke, with support from the National Institute of Child Health
      and Human Development, Autism Speaks, and Citizens United for Research in
      Epilepsy, that took place in Bethesda, Maryland, on May 29 and 30, 2012. The
      goals of this workshop were to highlight the clinical and biological
      relationships between ASD and epilepsy, to determine both short- and long-term
      goals that address research and treatment conundrums in individuals with both ASD
      and epilepsy, and to identify resources that can further both clinical and basic
      research. Topics discussed included epidemiology, genetics, environmental
      factors, common mechanisms, neuroimaging, neuropathology, neurophysiology,
      treatment, and research gaps and challenges in this unique population. 

PMID- 24089386
TI  - alpha-Synuclein in cutaneous autonomic nerves.
AB  - OBJECTIVE: To develop a cutaneous biomarker for Parkinson disease (PD). METHODS:
      Twenty patients with PD and 14 age- and sex-matched control subjects underwent
      examinations, autonomic testing, and skin biopsies at the distal leg, distal
      thigh, and proximal thigh. alpha-Synuclein deposition and the density of
      intraepidermal, sudomotor, and pilomotor nerve fibers were measured. alpha
      Synuclein deposition was normalized to nerve fiber density (the alpha-synuclein
      ratio). Results were compared with examination scores and autonomic function
      testing. RESULTS: Patients with PD had a distal sensory and autonomic neuropathy
      characterized by loss of intraepidermal and pilomotor fibers (p < 0.05 vs
      controls, all sites) and morphologic changes to sudomotor nerve fibers. Patients
      with PD had greater alpha-synuclein deposition and higher alpha-synuclein ratios
      compared with controls within pilomotor nerves and sudomotor nerves (p < 0.01,
      all sites) but not sensory nerves. Higher alpha-synuclein ratios correlated with
      Hoehn and Yahr scores (r = 0.58-0.71, p < 0.01), with sympathetic adrenergic
      function (r = -0.40 to -0.66, p < 0.01), and with parasympathetic function (r = 
      0.66 to -0.77, p > 0.01). CONCLUSIONS: We conclude that alpha-synuclein
      deposition is increased in cutaneous sympathetic adrenergic and sympathetic
      cholinergic fibers but not sensory fibers of patients with PD. Higher alpha
      synuclein deposition is associated with greater autonomic dysfunction and more
      advanced PD. These data suggest that measures of alpha-synuclein deposition in
      cutaneous autonomic nerves may be a useful biomarker in patients with PD.

PMID- 24089387
TI  - Comment: infection antedating autoimmunity-- shared mechanisms in the brain?
AB  - Anti-NMDA receptor (NMDAR) encephalitis is a well-recognized immunotherapy
      responsive condition, often diagnosed in younger individuals with characteristic
      clinical symptoms. In women, ovarian teratomas are frequently found and thought
      to trigger the antibody response against the NMDAR by ectopically expressing
      neuronal antigens. The present study describes the case of a patient with HSV
      encephalitis (HSVE) who develops a second episode of neurologic abnormalities,
      which is in fact NMDAR encephalitis.(1.) 

PMID- 24089388
TI  - Pretreatment cognitive deficits and treatment effects on attention in childhood
      absence epilepsy.
AB  - OBJECTIVE: To determine the neurocognitive deficits associated with newly
      diagnosed untreated childhood absence epilepsy (CAE), develop a model describing
      the factorial structure of items measuring academic achievement and 3
      neuropsychological constructs, and determine short-term differential
      neuropsychological effects on attention among ethosuximide, valproic acid, and
      lamotrigine. METHODS: Subjects with newly diagnosed CAE entering a double-blind,
      randomized controlled clinical trial had neuropsychological testing including
      assessments of general intellectual functioning, attention, memory, executive
      function, and achievement. Attention was reassessed at the week 16-20 visit.
      RESULTS: At study entry, 36% of the cohort exhibited attention deficits despite
      otherwise intact neurocognitive functioning. Structural equation modeling of
      baseline neuropsychological data revealed a direct sequential effect among
      attention, memory, executive function, and academic achievement. At the week 16
      20 visit, attention deficits persisted even if seizure freedom was attained. More
      subjects receiving valproic acid (49%) had attention deficits than subjects
      receiving ethosuximide (32%) or lamotrigine (24%) (p = 0.0006). Parental
      assessment did not reliably detect attention deficits before or after treatment
      (p < 0.0001). CONCLUSIONS: Children with CAE have a high rate of pretreatment
      attentional deficits that persist despite seizure freedom. Rates are
      disproportionately higher for valproic acid treatment compared with ethosuximide
      or lamotrigine. Parents do not recognize these attentional deficits. These
      deficits present a threat to academic achievement. Vigilant cognitive and
      behavioral assessment of these children is warranted. CLASSIFICATION OF EVIDENCE:
      This study provides Class I evidence that valproic acid is associated with more
      significant attentional dysfunction than ethosuximide or lamotrigine in children
      with newly diagnosed CAE.

PMID- 24089389
TI  - Absence in childhood absence epilepsy: the horse is out of the barn.
AB  - Clinicians typically breathe a sigh of relief when they make the diagnosis of
      childhood absence epilepsy. The history is classic-a normal young child with
      myriad brief periods of staring. The clinic visit is powerful when the phenomena
      are replicated by having the child hyperventilate. Finally, the EEG is
      definitive. The ability to demonstrate to a family the abrupt eruption and
      cessation of spike-wave activity provides a framework for them to understand what
      is happening to their child. Parents are usually reassured that there are very
      good therapies, that seizures are typically controlled, and that their child will
      "outgrow" it. However, data from the multicenter Childhood Absence Epilepsy Study
      Group are rewriting this narrative.(1-3.) 

PMID- 24089390
TI  - Herpes simplex virus-1 encephalitis can trigger anti-NMDA receptor encephalitis:
      case report.

PMID- 24089391
TI  - Is alpha-synuclein rising to the surface as a diagnostic biomarker for Parkinson
      disease?
AB  - In his historic manuscript on the "shaking palsy," James Parkinson expressed the
      hope "that some remedial process may ere long be discovered, by which, at least,
      the progress of the disease may be stopped."(1) Realization of that hope will
      require not only the discovery of a treatment that can halt or slow the
      progression of Parkinson disease (PD), but also the identification of early,
      accurate, and accessible biomarkers, for by the time the cardinal clinical signs
      of bradykinesia, rigidity, tremor, and postural instability appear, substantial
      destruction of nigrostriatal dopaminergic neurons has already occurred. 

PMID- 24089392
TI  - Risk of Parkinson disease after depression: a nationwide population-based study.
AB  - OBJECTIVE: To evaluate the risk of Parkinson disease (PD) among patients with
      depression by using the Taiwan National Health Insurance Research Database
      (NHIRD). METHODS: We conducted a retrospective study of a matched cohort of
      23,180 participants (4,634 patients with depression and 18,544 control patients)
      who were selected from the NHIRD. Patients were observed for a maximum of 10
      years to determine the rates of new-onset PD, and Cox regression was used to
      identify the predictors of PD. We also examined the risk of PD after excluding
      patients who were diagnosed with PD within 2 or 5 years after their depression
      diagnosis. A logistic regression model was used to identify risk factors
      associated with PD onset in patients with depression. RESULTS: During the 10-year
      follow-up period, 66 patients with depression (1.42%) and 97 control patients
      (0.52%) were diagnosed with PD. After adjusting for age and sex, patients with
      depression were 3.24 times more likely to develop PD (95% confidence interval
      2.36-4.44, p < 0.001) compared with the control patients. After excluding
      patients who were diagnosed with PD within 2 or 5 years after their depression
      diagnosis, patients with depression had a higher hazard ratio for developing PD
      than the control patients. The odds ratios for age (1.09) and difficult-to-treat
      depression (2.18) showed that each is an independent risk factor for PD in
      patients with depression. CONCLUSION: The likelihood of developing PD is greater
      among patients with depression than patients without depression. Depression may
      be an independent risk factor for PD.

PMID- 24089393
TI  - Air-spun PLA nanofibers modified with reductively sheddable hydrophilic surfaces
      for vascular tissue engineering: synthesis and surface modification.
AB  - Polylactide (PLA) is a class of promising biomaterials that hold great promise
      for various biological and biomedical applications, particularly in the field of
      vascular tissue engineering where it can be used as a fibrous mesh to coat the
      inside of vascular prostheses. However, its hydrophobic surface providing
      nonspecific interactions and its limited ability to further modifications are
      challenges that need to be overcome. Here, the development of new air-spun PLA
      nanofibers modified with hydrophilic surfaces exhibiting reduction response is
      reported. Surface-initiated atom transfer radical polymerization allows for
      grafting pendant oligo(ethylene oxide)-containing polymethacrylate (POEOMA) from
      PLA air-spun fibers labeled with disulfide linkages. The resulting PLA-ss-POEOMA
      fibers exhibit enhanced thermal stability and improved surface properties, as
      well as thiol-responsive shedding of hydrophilic POEOMA by the cleavage of its
      disulfide linkages in response to reductive reactions, thus tuning the surface
      properties. 

PMID- 24089394
TI  - Multisensory integration in early vestibular processing in mice: the encoding of
      passive vs. active motion.
AB  - The mouse has become an important model system for studying the cellular basis of
      learning and coding of heading by the vestibular system. Here we recorded from
      single neurons in the vestibular nuclei to understand how vestibular pathways
      encode self-motion under natural conditions, during which proprioceptive and
      motor-related signals as well as vestibular inputs provide feedback about an
      animal's movement through the world. We recorded neuronal responses in alert
      behaving mice focusing on a group of neurons, termed vestibular-only cells, that
      are known to control posture and project to higher-order centers. We found that
      the majority (70%, n = 21/30) of neurons were bimodal, in that they responded
      robustly to passive stimulation of proprioceptors as well as passive stimulation
      of the vestibular system. Additionally, the linear summation of a given neuron's
      vestibular and neck sensitivities predicted well its responses when both stimuli
      were applied simultaneously. In contrast, neuronal responses were suppressed when
      the same motion was actively generated, with the one striking exception that the
      activity of bimodal neurons similarly and robustly encoded head on body position
      in all conditions. Our results show that proprioceptive and motor-related signals
      are combined with vestibular information at the first central stage of vestibular
      processing in mice. We suggest that these results have important implications for
      understanding the multisensory integration underlying accurate postural control
      and the neural representation of directional heading in the head direction cell
      network of mice. 

PMID- 24089396
TI  - Dominant vs. nondominant arm advantage in mentally simulated actions in right
      handers.
AB  - Although plentiful data are available regarding mental states involving the
      dominant-right arm, the evidence for the nondominant-left arm is sparse. Here, we
      investigated whether right-handers can generate accurate predictions with either
      the right or the left arm. Fifteen adults carried out actual and mental arm
      movements in two directions with varying inertial resistance (inertial anisotropy
      phenomenon). We recorded actual and mental movement times and used the degree of
      their similarity as an indicator for the accuracy of motor imagery/prediction
      process. We found timing correspondences (isochrony) between actual and mental
      right arm movements in both rightward (low inertia resistance) and leftward (high
      inertia resistance) directions. Timing similarities between actual and mental
      left arm movements existed for the leftward direction (low inertia resistance)
      but not for the rightward direction (high inertia resistance). We found similar
      results when participants reaching towards the midline of the workspace, a result
      that excludes a hemispace effect. Electromyographic analysis during mental
      movements showed that arm muscles remained inactivate, thus eliminating a muscle
      activation strategy that could explain intermanual differences. Furthermore,
      motor-evoked potentials enhancement in both right and left biceps brachii during
      mental actions indicated that subjects were actively engaged in mental movement
      simulation and that the disadvantage of the left arm cannot be attributed to the
      nonactivation of the right motor cortex. Our findings suggest that predictive
      mechanisms are more robust for the right than the left arm in right-handers. We
      discussed these findings from the perspective of the internal models theory and
      the dynamic-dominance hypothesis of laterality. 

PMID- 24089395
TI  - Joint tuning for direction of motion and binocular disparity in macaque MT is
      largely separable.
AB  - Neurons in sensory cortical areas are tuned to multiple dimensions, or features,
      of their sensory space. Understanding how single neurons represent multiple
      features is of great interest for determining the informative dimensions of the
      neurons' response, the decoding algorithms appropriate for extracting this
      information from the neuronal population, and for determining where specific
      transformations occur along the visual hierarchy. Despite the established role of
      cortical area MT in judgments of motion and depth, it is not known how individual
      neurons jointly encode the two dimensions. We investigated the joint tuning of
      individual MT neurons for two visual features: direction of motion and binocular
      disparity, an important depth cue. We found that a separable, multiplicative
      combination of tuning for the two features can account for more than 90% of the
      variance in the joint tuning function for over 91% of MT neurons. These results
      suggest 1) that each feature can be read out independently from MT by simply
      averaging across the population without regard to the other feature and 2) that
      the inseparable representations seen in subsequent areas, such as MST, must be
      computed beyond MT. Intriguingly, we found that the remaining nonseparable
      component of the joint tuning function often manifested as small but systematic
      changes in the neurons' preferences for one feature as the other one was varied.
      We believe this reflects the local columnar organization of tuning for direction
      and binocular disparity in MT, indicating that joint tuning may provide a new
      tool with which to probe functional architecture. 

PMID- 24089399
TI  - Interjoint dynamic interaction during constrained human quiet standing examined
      by induced acceleration analysis.
AB  - Recent studies have demonstrated that human quiet standing is a multijoint
      movement, whereby the central nervous system (CNS) is required to deal with
      dynamic interactions among the joints to achieve optimal motor performance. The
      purpose of this study was to investigate how the CNS deals with such interjoint
      interaction during quiet standing by examining the relationship between the
      kinetics (torque) and kinematics (angular acceleration) within the multi-degree
      of freedom system. We modeled quiet standing as a double-link inverted pendulum
      involving both ankle and hip joints and conducted an "induced acceleration
      analysis." We found that the net ankle and hip torques induced angular
      accelerations of comparable magnitudes to the ankle (3.8 +/- 1.4 degrees /s(2)
      and 3.3 +/- 1.2 degrees /s(2)) and hip (9.1 +/- 3.2 degrees /s(2) and 10.5 +/-
      3.5 degrees /s(2)) joints, respectively. Angular accelerations induced by the net
      ankle and hip torques were modulated in a temporally antiphase pattern to one
      another in each of the two joints. These quantitative and temporal relationships
      allowed the angular accelerations induced by the two net torques to
      countercompensate one another, thereby substantially (~70%) reducing the
      resultant angular accelerations of the individual joints. These results suggest
      that, by taking advantage of the interjoint interaction, the CNS prevents the net
      torques from producing large amplitudes of the resultant angular accelerations
      when combined with the kinematic effects of all other torques in the chain. 

PMID- 24089397
TI  - Activity in mouse pedunculopontine tegmental nucleus reflects action and outcome
      in a decision-making task.
AB  - Recent studies across several mammalian species have revealed a distributed
      network of cortical and subcortical brain regions responsible for sensorimotor
      decision making. Many of these regions have been shown to be interconnected with
      the pedunculopontine tegmental nucleus (PPTg), a brain stem structure
      characterized by neuronal heterogeneity and thought to be involved in several
      cognitive and behavioral functions. However, whether this structure plays a
      general functional role in sensorimotor decision making is unclear. We
      hypothesized that, in the context of a sensorimotor task, activity in the PPTg
      would reflect task-related variables in a similar manner as do the cortical and
      subcortical regions with which it is anatomically associated. To examine this
      hypothesis, we recorded PPTg activity in mice performing an odor-cued spatial
      choice task requiring a stereotyped leftward or rightward orienting movement to
      obtain a reward. We studied single-neuron activity during epochs of the task
      related to movement preparation, execution, and outcome (i.e., whether or not the
      movement was rewarded). We found that a substantial proportion of neurons in the
      PPTg exhibited direction-selective activity during one or more of these epochs.
      In addition, an overlapping population of neurons reflected movement direction
      and reward outcome. These results suggest that the PPTg should be considered
      within the network of brain areas responsible for sensorimotor decision making
      and lay the foundation for future experiments to examine how the PPTg interacts
      with other regions to control sensory-guided motor output.

PMID- 24089398
TI  - Nicotinic receptors regulate the dynamic range of dopamine release in vivo.
AB  - Nicotinic acetylcholine receptors (nAChRs) are expressed presynaptically on
      dopamine axon terminals, and their activation by endogenous acetylcholine from
      striatal cholinergic interneurons enhances dopamine release both independently of
      and in concert with dopamine neuron activity. Acute nAChR inactivation is
      believed to enhance the contrast between low- and high-frequency dopamine cell
      activity. Although these studies reveal a key role for acute activation and
      inactivation of nAChRs in striatal microcircuitry, it remains unknown if chronic
      inactivation/desensitization of nAChRs can alter dopamine release dynamics. Using
      in vivo cyclic voltammetry in anaesthetized mice, we examined whether chronic
      inactivation of nAChRs modulates dopamine release across a parametric range of
      stimulation, varying both frequency and pulse number. Deletion of beta2*nAChRs
      and chronic nicotine exposure greatly diminished dopamine release across the
      entire range of stimulation parameters. In addition, we observed a facilitation
      of dopamine release at low frequency and pulse number in wild-type mice that is
      absent in the beta2* knockout and chronic nicotine mice. These data suggest that
      deletion or chronic desensitization of nAChRs reduces the dynamic range of
      dopamine release in response to dopamine cell activity, decreasing rather than
      increasing contrast between high and low dopamine activity. 

PMID- 24089400
TI  - A unifying model of concurrent spatial and temporal modularity in muscle
      activity.
AB  - Modularity in the central nervous system (CNS), i.e., the brain capability to
      generate a wide repertoire of movements by combining a small number of building
      blocks ("modules"), is thought to underlie the control of movement. Numerous
      studies reported evidence for such a modular organization by identifying
      invariant muscle activation patterns across various tasks. However, previous
      studies relied on decompositions differing in both the nature and dimensionality
      of the identified modules. Here, we derive a single framework that encompasses
      all influential models of muscle activation modularity. We introduce a new model
      (named space-by-time decomposition) that factorizes muscle activations into
      concurrent spatial and temporal modules. To infer these modules, we develop an
      algorithm, referred to as sample-based nonnegative matrix trifactorization
      (sNM3F). We test the space-by-time decomposition on a comprehensive
      electromyographic dataset recorded during execution of arm pointing movements and
      show that it provides a low-dimensional yet accurate, highly flexible and task
      relevant representation of muscle patterns. The extracted modules have a well
      characterized functional meaning and implement an efficient trade-off between
      replication of the original muscle patterns and task discriminability.
      Furthermore, they are compatible with the modules extracted from existing models,
      such as synchronous synergies and temporal primitives, and generalize time
      varying synergies. Our results indicate the effectiveness of a simultaneous but
      separate condensation of spatial and temporal dimensions of muscle patterns. The
      space-by-time decomposition accommodates a unified view of the hierarchical
      mapping from task parameters to coordinated muscle activations, which could be
      employed as a reference framework for studying compositional motor control.

PMID- 24089401
TI  - Functional difference in short- and long-latency interhemispheric inhibitions
      from active to resting hemisphere during a unilateral muscle contraction.
AB  - The aim of the present study was to investigate whether there is a functional
      difference in short-latency (SIHI) and long-latency (LIHI) interhemispheric
      inhibition from the active to the resting primary motor cortex (M1) with paired
      pulse transcranial magnetic stimulation during a unilateral muscle contraction.
      In nine healthy right-handed participants, IHI was tested from the dominant to
      the nondominant M1 and vice versa under resting conditions or during performance
      of a sustained unilateral muscle contraction with the right or left first dorsal
      interosseous muscle at 10% and 30% maximum voluntary contraction. To obtain
      measurements of SIHI and LIHI, a conditioning stimulus (CS) was applied over the
      M1 contralateral to the muscle contraction, followed by a test stimulus over the
      M1 ipsilateral to the muscle contraction at short (10 ms) and long (40 ms)
      interstimulus intervals. We used four CS intensities to investigate SIHI and LIHI
      from the active to the resting M1 systematically. The amount of IHI during the
      unilateral muscle contractions showed a significant difference between SIHI and
      LIHI, but the amount of IHI during the resting condition did not. In particular,
      SIHI during the muscle contractions, but not LIHI, significantly increased with
      increase in CS intensity compared with the resting condition. Laterality of IHI
      was not detected in any of the experimental conditions. The present study
      provides novel evidence that a functional difference between SIHI and LIHI from
      the active to the resting M1 exists during unilateral muscle contractions. 

PMID- 24089402
TI  - The dynamics of invariant object recognition in the human visual system.
AB  - The human visual system can rapidly recognize objects despite transformations
      that alter their appearance. The precise timing of when the brain computes neural
      representations that are invariant to particular transformations, however, has
      not been mapped in humans. Here we employ magnetoencephalography decoding
      analysis to measure the dynamics of size- and position-invariant visual
      information development in the ventral visual stream. With this method we can
      read out the identity of objects beginning as early as 60 ms. Size- and position
      invariant visual information appear around 125 ms and 150 ms, respectively, and
      both develop in stages, with invariance to smaller transformations arising before
      invariance to larger transformations. Additionally, the magnetoencephalography
      sensor activity localizes to neural sources that are in the most posterior
      occipital regions at the early decoding times and then move temporally as
      invariant information develops. These results provide previously unknown
      latencies for key stages of human-invariant object recognition, as well as new
      and compelling evidence for a feed-forward hierarchical model of invariant object
      recognition where invariance increases at each successive visual area along the
      ventral stream. 

PMID- 24089403
TI  - Bayesian decoding using unsorted spikes in the rat hippocampus.
AB  - A fundamental task in neuroscience is to understand how neural ensembles
      represent information. Population decoding is a useful tool to extract
      information from neuronal populations based on the ensemble spiking activity. We
      propose a novel Bayesian decoding paradigm to decode unsorted spikes in the rat
      hippocampus. Our approach uses a direct mapping between spike waveform features
      and covariates of interest and avoids accumulation of spike sorting errors. Our
      decoding paradigm is nonparametric, encoding model-free for representing stimuli,
      and extracts information from all available spikes and their waveform features.
      We apply the proposed Bayesian decoding algorithm to a position reconstruction
      task for freely behaving rats based on tetrode recordings of rat hippocampal
      neuronal activity. Our detailed decoding analyses demonstrate that our approach
      is efficient and better utilizes the available information in the nonsortable
      hash than the standard sorting-based decoding algorithm. Our approach can be
      adapted to an online encoding/decoding framework for applications that require
      real-time decoding, such as brain-machine interfaces. 

PMID- 24089404
TI  - Dissociating the neural bases of repetition-priming and adaptation in the human
      brain for faces.
AB  - The repetition of a given stimulus leads to the attenuation of the functional
      magnetic resonance imaging (fMRI) signal compared with unrepeated stimuli, a
      phenomenon called fMRI adaptation or repetition suppression (RS). Previous
      studies have related RS of the fMRI signal behaviorally both to improved
      performance for the repeated stimulus (priming) and to shifts of perception away
      from the first stimulus (adaptation-related aftereffects). Here we used identical
      task (sex discrimination), trial structure [stimulus 1 (S1): 3,000 ms,
      interstimulus interval: 600 ms, stimulus 2 (S2): 300 ms], and S2 stimuli
      (androgynous faces) to test how RS of the face-specific areas of the occipito
      temporal cortex relates to priming and aftereffects. By varying S1, we could
      induce priming (significantly faster reaction times when S1 and S2 were identical
      compared with different images) as well as sex-specific aftereffect [an increased
      ratio of male responses if S1 was a female face compared with ambiguous faces or
      to Fourier-randomized noise (FOU) images]. Presenting any face as S1 led to
      significant RS of the blood oxygen level-dependent signal in the fusiform and
      occipital face areas as well as in the lateral occipital cortex of both
      hemispheres compared with FOU, reflecting stimulus category-specific encoding.
      Additionally, while sex-specific adaptation effects were only observed in
      occipital face areas, primed trials led to a signal reduction in both face
      selective regions. Altogether, these results suggest the differential neural
      mechanisms of adaptation and repetition priming.

PMID- 24089405
TI  - Sulfate metabolites provide an intracellular pool for resveratrol generation and
      induce autophagy with senescence.
AB  - The phytochemical resveratrol has been shown to exert numerous health benefits in
      preclinical studies, but its rapid metabolism and resulting poor bioavailability
      may limit translation of these effects to humans. Resveratrol metabolites might
      contribute to in vivo activity through regeneration of the parent compound. We
      present quantitation of sulfate and glucuronide conjugates of resveratrol in
      human plasma and tissue after repeated ingestion of resveratrol by volunteers and
      cancer patients, respectively. Subsequent pharmacokinetic characterization of a
      mixture of resveratrol-3-O-sulfate and resveratrol-4'-O-sulfate in mice showed
      that these metabolites are absorbed orally but have low bioavailabilities of ~14
      and 3%, respectively. Sulfate hydrolysis in vivo liberated free resveratrol,
      which accounted for ~2% of the total resveratrol species present in mouse plasma.
      Monosulfate metabolites were also converted to the parent in human colorectal
      cells. The extent of cellular uptake was dependent on specific membrane
      transporters and dictated antiproliferative activity. Sulfate metabolites induced
      autophagy and senescence in human cancer cells; these effects were abrogated by
      inclusion of a sulfatase inhibitor, which reduced intracellular resveratrol.
      Together, our findings suggest that resveratrol is delivered to target tissues in
      a stable sulfate-conjugated form and that the parent compound is gradually
      regenerated in selected cells and may give rise to the beneficial effects in
      vivo. At doses considered to be safe in humans, resveratrol generated via this
      route may be of greater importance than the unmetabolized form. 

PMID- 24089406
TI  - A human type 5 adenovirus-based tuberculosis vaccine induces robust T cell
      responses in humans despite preexisting anti-adenovirus immunity.
AB  - There is an urgent need to develop new tuberculosis (TB) vaccines to safely and
      effectively boost Bacille Calmette-Guerin (BCG)-triggered T cell immunity in
      humans. AdHu5Ag85A is a recombinant human type 5 adenovirus (AdHu5)-based TB
      vaccine with demonstrated efficacy in a number of animal species, yet it remains
      to be translated to human applications. In this phase 1 study, we evaluated the
      safety and immunogenicity of AdHu5Ag85A in both BCG-naive and previously BCG
      immunized healthy adults. Intramuscular immunization of AdHu5Ag85A was safe and
      well tolerated in both trial volunteer groups. Moreover, although AdHu5Ag85A was
      immunogenic in both trial volunteer groups, it much more potently boosted
      polyfunctional CD4(+) and CD8(+) T cell immunity in previously BCG-vaccinated
      volunteers. Furthermore, despite prevalent preexisting anti-AdHu5 humoral
      immunity in most of the trial volunteers, we found little evidence that such
      preexisting anti-AdHu5 immunity significantly dampened the potency of AdHu5Ag85A
      vaccine. This study supports further clinical investigations of the AdHu5Ag85A
      vaccine for human applications. It also suggests that the widely perceived
      negative effect of preexisting anti-AdHu5 immunity may not be universally applied
      to all AdHu5-based vaccines against different types of human pathogens. 

PMID- 24089407
TI  - Model system to define pharmacokinetic requirements for antimalarial drug
      efficacy.
AB  - Malaria presents a tremendous public health burden, and new therapies are needed.
      Massive compound libraries screened against Plasmodium falciparum have yielded
      thousands of lead compounds, resulting in an acute need for rational criteria to
      select the best candidates for development. We reasoned that, akin to
      antibacterials, antimalarials might have an essential pharmacokinetic requirement
      for efficacy: action governed either by total exposure or peak concentration
      (AUC/CMAX), or by duration above a defined minimum concentration [time above
      minimum inhibitory concentration (TMIC)]. We devised an in vitro system for P.
      falciparum, capable of mimicking the dynamic fluctuations of a drug in vivo.
      Using this apparatus, we find that chloroquine is TMIC-dependent, whereas the
      efficacy of artemisinin is driven by CMAX. The latter was confirmed in a mouse
      model of malaria. These characteristics can explain the clinical success of two
      antimalarial drugs with widely different kinetics in humans. Chloroquine, which
      persists for weeks, is ideally suited for its TMIC mechanism, whereas great
      efficacy despite short exposure (t1/2 in blood 3 hours or less) is attained by
      CMAX-driven artemisinins. This validated preclinical model system can be used to
      select those antimalarial lead compounds whose CMAX or TMIC requirement for
      efficacy matches pharmacokinetics obtained in vivo. The apparatus can also be
      used to explore the kinetic dependence of other pharmacodynamic endpoints in
      parasites. 

PMID- 24089409
TI  - High-throughput methods for combinatorial drug discovery.
AB  - A more nuanced approach to drug design is to use multiple drugs in combination to
      target interacting or complementary pathways. Drug combination treatments have
      shown higher efficacy, fewer side effects, and less toxicity compared to single
      drug treatment. In this Review, we focus on the use of high-throughput biological
      measurements (genetics, transcripts, and chemogenetic interactions) and the
      computational methods they necessitate to further combinatorial drug design
      (CDD). We highlight the state-of-the-art analytical methods, including network
      analysis, integrative informatics, and dynamic molecular modeling, that have been
      used successfully in CDD. Finally, we present an exhaustive list of the publicly
      available data and methodological resources available to the community. Such next
      generation technologies that enable the measurement of millions of cellular data
      points simultaneously may usher in a new paradigm in drug discovery, where
      medicine is viewed as a system of interacting genes and pathways rather than the
      result of an individual protein or gene. 

PMID- 24089408
TI  - Peripheral blood mononuclear cell gene expression profiles predict poor outcome
      in idiopathic pulmonary fibrosis.
AB  - We aimed to identify peripheral blood mononuclear cell (PBMC) gene expression
      profiles predictive of poor outcomes in idiopathic pulmonary fibrosis (IPF) by
      performing microarray experiments of PBMCs in discovery and replication cohorts
      of IPF patients. Microarray analyses identified 52 genes associated with
      transplant-free survival (TFS) in the discovery cohort. Clustering the microarray
      samples of the replication cohort using the 52-gene outcome-predictive signature
      distinguished two patient groups with significant differences in TFS. We studied
      the pathways associated with TFS in each independent microarray cohort and
      identified decreased expression of "The costimulatory signal during T cell
      activation" Biocarta pathway and, in particular, the genes CD28, ICOS, LCK, and
      ITK, results confirmed by quantitative reverse transcription polymerase chain
      reaction (qRT-PCR). A proportional hazards model, including the qRT-PCR
      expression of CD28, ICOS, LCK, and ITK along with patient's age, gender, and
      percent predicted forced vital capacity (FVC%), demonstrated an area under the
      receiver operating characteristic curve of 78.5% at 2.4 months for death and lung
      transplant prediction in the replication cohort. To evaluate the potential
      cellular source of CD28, ICOS, LCK, and ITK expression, we analyzed and found
      significant correlation of these genes with the PBMC percentage of CD4(+)CD28(+)
      T cells in the replication cohort. Our results suggest that CD28, ICOS, LCK, and
      ITK are potential outcome biomarkers in IPF and should be further evaluated for
      patient prioritization for lung transplantation and stratification in drug
      studies. 

PMID- 24089411
TI  - Congestive heart failure in rats is associated with increased collecting duct
      vasopressin sensitivity and vasopressin type 2 receptor reexternalization.
AB  - A number of studies have shown that rats with congestive heart failure (CHF) have
      increased protein levels of the vasopressin (AVP)-regulated water channel
      aquaporin-2 (AQP2) even during conditions with unchanged circulating levels of
      AVP, suggesting an increase in the sensitivity of the AVP type 2 (V2) receptor in
      experimental CHF. The present study was aimed at investigating AVP signaling in
      rats with moderate CHF (left ventricular end diastolic pressure >10 mmHg; normal
      plasma AVP levels) induced by ligation of the left anterior descending coronary
      artery. Sham-operated rats were used as controls. Western blotting analyses
      revealed an increased abundance of AQP2 in renal cortex (+33 +/- 9% of sham; P <
      0.05) and in inner medulla (IM) (+54 +/- 15% of sham; P < 0.05) in CHF rats
      compared with sham-operated controls. Dose-response studies on isolated
      collecting ducts (CDs) showed an increased accumulation of cAMP in response to
      AVP in CHF rats compared with controls. V2 receptor surface-binding studies in
      isolated IMCDs showed a marked and comparable AVP-induced V2 receptor
      internalization in response to AVP in both CHF and control rats. As expected V2
      receptor surface binding remained low after AVP challenge in control rats. In
      contrast to this, V2 receptor surface binding returned to pre-AVP levels within
      30 min in the CHF rats, indicating an obtained recycling ability of the V2
      receptor in CHF. Together the results indicate the presence of an increased AVP
      sensitivity in the CDs from CHF rats, associated with an acquired recycling
      ability of the V2 receptor.

PMID- 24089410
TI  - Molecular evidence for a role for K(+)-Cl(-) cotransporters in the kidney.
AB  - K(+)-Cl(-) cotransporter (KCC) isoforms 3 (KCC3) and 4 (KCC4) are expressed at
      the basolateral membrane of proximal convoluted tubule cells, and KCC4 is present
      in the basolateral membrane of the thick ascending loop of Henle's limb and alpha
      intercalated cells of the collecting duct. Little is known, however, about the
      physiological roles of these transporters in the kidney. We evaluated KCC3 and
      KCC4 mRNA and protein expression levels and intrarenal distribution in male
      Wistar rats or C57 mice under five experimental conditions: hyperglycemia after a
      single dose of streptozotocin, a low-salt diet, metabolic acidosis induced by
      ammonium chloride in drinking water, and low- or high-K(+) diets. Both KCC3 mRNA
      and protein expression were increased during hyperglycemia in the renal cortex
      and at the basolateral membrane of proximal tubule cells but not with a low-salt
      diet or acidosis. In contrast, KCC4 protein expression was increased by a low
      sodium diet in the whole kidney and by metabolic acidosis in the renal outer
      medulla, specifically at the basolateral membrane of alpha-intercalated cells.
      The increased protein expression of KCC4 by a low-salt diet was also observed in
      WNK4 knockout mice, suggesting that upregulation of KCC4 in these circumstances
      is not WNK4 dependent. No change in KCC3 or KCC4 protein expression was observed
      under low- or high-K(+) diets. Our data are consistent with a role for KCC3 in
      the proximal tubule glucose reabsorption mechanism and for KCC4 in salt
      reabsorption of the thick ascending loop of Henle's loop and acid secretion of
      the collecting duct.

PMID- 24089412
TI  - Elucidation of the distal convoluted tubule transcriptome identifies new
      candidate genes involved in renal Mg(2+) handling.
AB  - The kidney plays a key role in the maintenance of Mg(2+) homeostasis.
      Specifically, the distal convoluted tubule (DCT) is instrumental in the fine
      tuning of renal Mg(2+) handling. In recent years, hereditary Mg(2+) transport
      disorders have helped to identify important players in DCT Mg(2+) homeostasis.
      Nevertheless, several proteins involved in DCT-mediated Mg(2+) reabsorption
      remain to be discovered, and a full expression profile of this complex nephron
      segment may facilitate the discovery of new Mg(2+)-related genes. Here, we report
      Mg(2+)-sensitive expression of the DCT transcriptome. To this end, transgenic
      mice expressing enhanced green fluorescent protein under a DCT-specific
      parvalbumin promoter were subjected to Mg(2+)-deficient or Mg(2+)-enriched diets.
      Subsequently, the Complex Object Parametric Analyzer and Sorter allowed, for the
      first time, isolation of enhanced green fluorescent protein-positive DCT cells.
      RNA extracts thereof were analyzed by DNA microarrays comparing high versus low
      Mg(2+) to identify Mg(2+) regulatory genes. Based on statistical significance and
      a fold change of at least 2, 46 genes showed differential expression. Several
      known magnesiotropic genes, such as transient receptor potential cation channel,
      subfamily M, member 6 (Trpm6), and Parvalbumin, were upregulated under low
      dietary Mg(2+). Moreover, new genes were identified that are potentially involved
      in renal Mg(2+) handling. To confirm that the selected candidate genes were
      regulated by dietary Mg(2+) availability, the expression levels of solute carrier
      family 41, member 3 (Slc41a3), pterin-4 alpha-carbinolamine
      dehydratase/dimerization cofactor of hepatocyte nuclear factor-1alpha (Pcbd1),
      TBC1 domain family, member 4 (Tbc1d4), and uromodulin (Umod) were determined by
      RT-PCR analysis. Indeed, all four genes show significant upregulation in the DCT
      of mice fed a Mg(2+)-deficient diet. By elucidating the Mg(2+)-sensitive DCT
      transcriptome, new candidate genes in renal Mg(2+) handling have been identified.

PMID- 24089413
TI  - A test of the hypothesis that oxalate secretion produces proximal tubule
      crystallization in primary hyperoxaluria type I.
AB  - The sequence of events by which primary hyperoxaluria type 1 (PH1) causes renal
      failure is unclear. We hypothesize that proximal tubule (PT) is vulnerable
      because oxalate secretion raises calcium oxalate (CaOx) supersaturation (SS)
      there, leading to crystal formation and cellular injury. We studied cortical and
      papillary biopsies from two PH1 patients with preserved renal function, and seven
      native kidneys removed from four patients at the time of transplant, after short
      term (2) or longer term (2) dialysis. In these patients, and another five PH1
      patients without renal failure, we calculated oxalate secretion, and estimated PT
      CaOx SS. Plasma oxalate was elevated in all PH1 patients and inverse to
      creatinine clearance. Renal secretion of oxalate was present in all PH1 but rare
      in controls. PT CaOx SS was >1 in all nonpyridoxine-responsive PH1 before
      transplant and most marked in patients who developed end stage renal disease
      (ESRD). PT from PH1 with preserved renal function had birefringent crystals,
      confirming the presence of CaOx SS, but had no evidence of cortical inflammation
      or scarring by histopathology or hyaluronan staining. PH1 with short ESRD showed
      CaOx deposition and hyaluronan staining particularly at the corticomedullary
      junction in distal PT while cortical collecting ducts were spared. Longer ESRD
      showed widespread cortical CaOx, and in both groups papillary tissue had marked
      intratubular CaOx deposits and fibrosis. CaOx SS in PT causes CaOx crystal
      formation, and CaOx deposition in distal PT appears to be associated with ESRD.
      Minimizing PT CaOx SS may be important for preserving renal function in PH1.

PMID- 24089415
TI  - Delivery of differentiation factors by mesoporous silica particles assists
      advanced differentiation of transplanted murine embryonic stem cells.
AB  - Stem cell transplantation holds great hope for the replacement of damaged cells
      in the nervous system. However, poor long-term survival after transplantation and
      insufficiently robust differentiation of stem cells into specialized cell types
      in vivo remain major obstacles for clinical application. Here, we report the
      development of a novel technological approach for the local delivery of exogenous
      trophic factor mimetics to transplanted cells using specifically designed silica
      nanoporous particles. We demonstrated that delivering Cintrofin and Gliafin,
      established peptide mimetics of the ciliary neurotrophic factor and glial cell
      line-derived neurotrophic factor, respectively, with these particles enabled not
      only robust functional differentiation of motor neurons from transplanted
      embryonic stem cells but also their long-term survival in vivo. We propose that
      the delivery of growth factors by mesoporous nanoparticles is a potentially
      versatile and widely applicable strategy for efficient differentiation and
      functional integration of stem cell derivatives upon transplantation. 

PMID- 24089414
TI  - Activation of human mesenchymal stem cells impacts their therapeutic abilities in
      lung injury by increasing interleukin (IL)-10 and IL-1RN levels.
AB  - Acute respiratory distress syndrome (ARDS) is an important cause of morbidity and
      mortality, with no currently effective therapies. Several preclinical studies
      have shown that human mesenchymal stem cells (hMSCs) have therapeutic potential
      for patients with ARDS because of their immunomodulatory properties. The clinical
      use of hMSCs has some limitations, such as the extensive manipulation required to
      isolate the cells from bone marrow aspirates and the heterogeneity in their anti
      inflammatory effect in animal models and clinical trials. The objective of this
      study was to improve the protective anti-inflammatory capacity of hMSCs by
      evaluating the consequences of preactivating hMSCs before use in a murine model
      of ARDS. We injected endotoxemic mice with minimally manipulated hMSCs isolated
      from the bone marrow of vertebral bodies with or without prior activation with
      serum from ARDS patients. Minimally manipulated hMSCs were more efficient at
      reducing lung inflammation compared with isolated and in vitro expanded hMSCs
      obtained from bone marrow aspirates. Where the most important effect was observed
      was with the activated hMSCs, independent of their source, which resulted in
      increased expression of interleukin (IL)-10 and IL-1 receptor antagonist (RN),
      which was associated with enhancement of their protective capacity by reduction
      of the lung injury score, development of pulmonary edema, and accumulation of
      bronchoalveolar lavage inflammatory cells and cytokines compared with
      nonactivated cells. This study demonstrates that a low manipulation during hMSC
      isolation and expansion increases, together with preactivation prior to the
      therapeutic use of hMSCs, would ensure an appropriate immunomodulatory phenotype
      of the hMSCs, reducing the heterogeneity in their anti-inflammatory effect. 

PMID- 24089416
TI  - Polymorphisms in genes involved in folate metabolism modify the association of
      dietary and circulating folate and vitamin B-6 with cervical neoplasia.
AB  - High folate intake has been suggested as an important factor in cancer
      prevention; however, previous studies on the relation among folate intake, serum
      folate, and plasma homocysteine (hcy) are controversial. We conducted a hospital
      based, case-control study in Brazil investigating associations between dietary
      and circulating vitamins B-6 and B-12 and folate, hcy, genotypes of folate
      metabolizing enzyme methylenetetrahydrofolate reductase (MTHFR C677T, A1298C), 5
      methyltetrahydrofolate-homocysteine methyltransferase (MTR A2756G), methionine
      synthase reductase (MTRR A66G), and reduced folate carrier (RFC1 G80A) and risk
      of cervical intraepithelial neoplasia (CIN) grades 1 (CIN1), 2 (CIN2), and 3
      (CIN3). The study was composed by 453 controls, 140 CIN1, 126 CIN2, and 231 CIN3.
      We investigated the joint effects of genetic variants of folate-related genes
      using genetic risk scores (GRSs) by summing the number of risk alleles for CIN1
      and CIN2+ (CIN2 and CIN3 cases). The OR (95% CI) for CIN1 and CIN2+ per each risk
      allele were 1.29 (1.01, 1.65) and 1.22 (1.01, 1.46), respectively. An association
      between folate intake and CIN2+ was observed only after stratification according
      to GRS: crude OR (95% CI) for lower folate intake and GRS >= 4 was 1.67 (0.92,
      3.04) (P-trend < 0.001) compared with higher folate intake (above the median) and
      GRS <= 3. The CIN2+ risk of lower serum vitamin B-6 and GRS >= 4 was 2.14 (0.92,
      5.02) (P-trend = 0.05) and lower serum folate (below the median) and GRS >= 4 was
      0.49 (0.20, 1.17) (P-trend = 0.05) after adjustment for confounding variables and
      human papillomavirus infection. Our data suggest that polymorphisms in genes
      related to folate metabolism modify the association of dietary and circulating
      folate and vitamin B-6 with cervical neoplasia.

PMID- 24089417
TI  - Infant feeding patterns are associated with cardiovascular structures and
      function in childhood.
AB  - Nutrition in infancy seems to be associated with cardiovascular disease and its
      risk factors in adulthood. These associations may be explained by cardiovascular
      developmental adaptations in childhood in response to specific infant feeding
      patterns. The aim of this study was to assess whether duration and exclusivity of
      breastfeeding and timing of introduction of solid foods affect cardiovascular
      development in childhood. In a population-based prospective cohort study from
      fetal life onward, information about duration and exclusivity of breastfeeding
      and timing of introduction of solid foods was obtained from delivery reports and
      questionnaires. Blood pressure, carotid-femoral pulse wave velocity (PWV), left
      atrial diameter (LAD), aortic root diameter (AOD), left ventricular (LV) mass,
      and fractional shortening (FS) were measured at a median age of 6.0 y (95% range:
      5.6-7.4 y). Analyses were based on 5003 children. Age at introduction of solid
      foods was negatively associated with systolic and diastolic blood pressure at the
      age of 6 y. Compared with children who had ever been breast-fed, never-breast-fed
      children had a higher carotid-femoral PWV (beta: 0.13 m/s; 95% CI: 0.03, 0.24
      m/s), a smaller LAD (beta: -0.29 mm; 95% CI: -0.55, -0.03 mm), and less LV mass
      (beta:-1.46 g; 95% CI: -2.41, -0.52 g) at the age of 6 y. Among breast-fed
      children, duration and exclusivity were not associated with cardiovascular
      structures or function. Breastfeeding pattern and age at introduction of solid
      foods were not associated with AOD or FS. Feeding patterns in infancy may
      influence cardiovascular development in childhood. Further research is required
      to replicate these findings and to investigate whether these changes contribute
      to an increased risk of cardiovascular disease in later life. 

PMID- 24089418
TI  - Midlife iron status is inversely associated with subsequent cognitive
      performance, particularly in perimenopausal women.
AB  - The link between iron status and cognition has been established in infants and
      children, yet evidence in adults is scant and heterogeneous. We examined sex- and
      menopause-specific cross-time associations of iron status with cognition in the
      French Supplementation en Vitamines et Mineraux Antioxydants Study cohort (1539
      men, 1431 pre-/perimenopausal women, 962 postmenopausal women). Serum ferritin
      and hemoglobin data were obtained in 1995. Cognition was assessed after a mean of
      13 y through 6 validated instruments, including the RI-48 cued recall test,
      phonemic and semantic fluency tasks, forward and backward digit span tasks, and a
      trail-making test. The standardized individual test scores were summed to form a
      composite cognitive performance measure. Associations between ferritin and
      hemoglobin and subsequent cognitive performance were examined through
      multivariable linear regression. Among men, no significant associations were
      observed. In postmenopausal women, an inverse association was found between
      ferritin and phonemic fluency (adjusted beta: -0.11; 95% CI: -0.21, -0.01).
      Significant inverse associations between ferritin and both the composite
      cognitive measure (adjusted beta: -0.09; 95% CI: -0.17, -0.00) and the forward
      digit span scores (adjusted beta: -0.13; 95% CI: -0.22, -0.03) were observed only
      among premenopausal women aged >= 46 y at baseline. No significant findings with
      hemoglobin emerged. This study supports an inverse association between midlife
      iron status and subsequent cognitive performance that is sex- and menopause
      dependent. Given the urgent need for prevention research on age-related
      disorders, future investigations of iron status and cognition are warranted. The
      study is registered at www.clinicaltrials.gov as NCT00272428.

PMID- 24089419
TI  - Household food insecurity is associated with higher child undernutrition in
      Bangladesh, Ethiopia, and Vietnam, but the effect is not mediated by child
      dietary diversity.
AB  - Household food insecurity (HFI) is a recognized underlying determinant of child
      undernutrition, but evidence of associations between HFI and child undernutrition
      is mixed. The purpose of this study was to investigate if HFI is associated with
      undernutrition in children aged 6-59.9 mo in Bangladesh (n = 2356), Ethiopia (n =
      3422), and Vietnam (n = 3075) and if child dietary diversity (DD) mediated this
      effect. We used baseline survey data from the Alive & Thrive project. Logistic
      regression, adjusting for potential confounding factors, was used to determine
      the magnitude and significance of the association of HFI with stunting,
      underweight, and wasting. The mediating effect of child DD was tested by using a
      Sobel-Goodman mediation test. The prevalences of HFI were 66%, 40%, and 32% in
      Ethiopia, Vietnam, and Bangladesh, respectively. The prevalences of stunting,
      underweight, and wasting were higher in Bangladesh (47.1%, 43.7%, and 19.1%,
      respectively) and Ethiopia (50.7%, 27.5%, and 5.9%, respectively) than in Vietnam
      (20.7%, 15.8%, and 5%, respectively). In the adjusted models, the odds of being
      stunted or underweight were significantly higher for children in severely food
      insecure households in Bangladesh (stunting OR: 1.36; 95% CI: 1.05, 1.76;
      underweight OR: 1.28; 95% CI: 0.99, 1.65) and Ethiopia (stunting OR: 1.48; 95%
      CI: 1.09, 2.00; underweight OR: 1.68; 95% CI: 1.22, 2.30) and in moderately food
      insecure households in Vietnam (stunting OR: 1.39; 95% CI: 1.16, 1.65;
      underweight OR: 1.69; 95% CI: 1.28, 2.23). HFI was significantly associated with
      wasting in Bangladesh where close to 1 in 5 children demonstrated wasting. Child
      DD did not mediate the relation between HFI and undernutrition in any of the
      countries. Further research is recommended to investigate potential mediators in
      this pathway. 

PMID- 24089420
TI  - Divalent metal transporter 1 (Dmt1) mediates copper transport in the duodenum of
      iron-deficient rats and when overexpressed in iron-deprived HEK-293 cells.
AB  - Intracellular copper-binding proteins (metallothionein I/II) and a copper
      exporter (Menkes copper-transporting ATPase) are upregulated in duodenal
      enterocytes from iron-deficient rats, consistent with copper accumulation in the
      intestinal mucosa. How copper enters enterocytes during iron deficiency is,
      however, not clear. Divalent metal transporter 1 (Dmt1), the predominant iron
      importer in the mammalian duodenum, also transports other metal ions, possibly
      including copper. Given this possibility and that Dmt1 expression is upregulated
      by iron deprivation, we sought to test the hypothesis that Dmt1 transports copper
      during iron deficiency. Two model systems were utilized: the Belgrade (b) rat,
      expressing mutant Dmt1, and an inducible Dmt1-overexpression cell culture system.
      Mutant rats (b/b) were fed a semipurified, AIN93G-based control diet and
      phenotypically normal littermates (+/b) were fed control or iron-deficient diets
      for ~14 wk. An everted gut sleeve technique and a colorimetric copper
      quantification assay were utilized to assess duodenal copper transport. The
      control diet-fed +/b rats had normal hematological parameters, whereas iron
      deprived +/b and b/b rats were iron deficient and Dmt1 mRNA and protein levels
      increased. Importantly, duodenal copper transport was similar in the control +/b
      and b/b rats; however, it significantly increased (~4-fold) in the iron-deprived
      +/b rats. Additional experiments in Dmt1 overexpressing HEK-293 cells showed that
      copper ((64)Cu) uptake was stimulated (~3-fold) in the presence of an iron
      chelator. Dmt1 transcript stabilization due to a 3' iron-responsive element was
      also documented, likely contributing to increased transport activity. In summary,
      these studies suggest that Dmt1 enhances copper uptake into duodenal enterocytes
      during iron deprivation.

PMID- 24089422
TI  - Gastric and colonic zinc transporter ZIP11 (Slc39a11) in mice responds to dietary
      zinc and exhibits nuclear localization.
AB  - Zinc transporters have been characterized to further understand the absorption
      and metabolism of dietary zinc. Our goal was to characterize zinc transporter
      Slc39a11 (ZIP11) expression and its subcellular localization within cells of the
      murine gastrointestinal tract of mice and to determine if dietary zinc regulates
      ZIP11. The greatest ZIP11 expression was in the stomach, cecum, and colon. Both
      Zip11 mRNA and ZIP11 protein were shown to be downregulated during dietary zinc
      restriction (<1 mg Zn/kg) in the murine stomach tissue but were unaffected in the
      colon. Acute repletion with zinc did not restore Zip11 mRNA levels in the
      stomach. Immunohistochemistry (IHC) revealed high ZIP11 levels in the lower
      regions of gastric glands and parietal cells of the stomach. IHC analysis of the
      colon showed a marked ZIP11 abundance within the cytoplasm of the colonic
      epithelial cells. IHC also showed an increase in ZIP11 expression in the colon
      during zinc restriction. There is a robust abundance of ZIP11 in the nuclei of
      cells of both stomach and colon. Our experiments suggest that when dietary zinc
      intake is compromised, the colon may increase zinc transporter expression to
      improve the efficiency for absorption via increased expression of specific zinc
      transporters, including ZIP11 and also zinc transporter Slc39a4. In conclusion,
      ZIP11 is highly expressed within the murine stomach and colon and appears to be
      partially regulated by dietary zinc intake within these tissues. ZIP11 may play a
      specialized role in zinc homeostasis within these tissues, helping to maintain
      mucosal integrity and function. 

PMID- 24089421
TI  - Dietary factors influence production of the soy isoflavone metabolite s-(-)equol
      in healthy adults.
AB  - S-(-)equol, an intestinally derived metabolite of the soy isoflavone daidzein, is
      proposed to enhance the efficacy of soy diets. Adults differ in their ability to
      produce equol when consuming soy foods for reasons that remain unclear.
      Therefore, we performed a comprehensive dietary analysis of 143 macro- and
      micronutrients in 159 healthy adults in the United States (n = 89) and Australia
      (n = 70) to determine whether the intake of specific nutrients favors equol
      production. Three-d diet records were collected and analyzed using Nutrition Data
      System for Research software and S-(-)equol was measured in urine by mass
      spectrometry. Additionally, in a subset of equol producers and nonproducers (n =
      10/group), we examined the long-term stability of equol producer status by
      retesting 12, 18, and 24 mo later. Finally, the effect of oral administration of
      the antibiotic metronidazole (500 mg/d for 7 d) on equol production was examined
      in 5 adults monitored during a 4-mo follow-up period. Equol producers accounted
      for 30.3% and 28.6% of the United States and Australian participants,
      respectively (overall frequency, 29.6%). No significant differences were observed
      for total protein, carbohydrate, fat, saturated fat, or fiber intakes between
      equol producers and nonproducers. However, principal component analysis revealed
      differences in several nutrients, including higher intakes of polyunsaturated
      fatty acids (P = 0.039), maltose (P = 0.02), and vitamins A (P = 0.01) and E (P =
      0.035) and a lower intake of total cholesterol (P = 0.010) in equol producers.
      During a 2-y period, equol producer status remained unchanged in all nonproducers
      and in 80% of equol producers, whereas metronidazole abolished equol production
      in only 20% of participants. In conclusion, these findings suggest that major
      differences in the macronutrient content of the diet appear not to influence
      equol production, but subtle differences in some nutrients may influence the
      ability to produce equol, which was a relatively stable phenomenon. 

PMID- 24089423
TI  - Group cognitive behavioural therapy and group recreational activity for adults
      with autism spectrum disorders: a preliminary randomized controlled trial.
AB  - Although adults with autism spectrum disorder are an increasingly identified
      patient population, few treatment options are available. This preliminary
      randomized controlled open trial with a parallel design developed two group
      interventions for adults with autism spectrum disorders and intelligence within
      the normal range: cognitive behavioural therapy and recreational activity. Both
      interventions comprised 36 weekly 3-h sessions led by two therapists in groups of
      6-8 patients. A total of 68 psychiatric patients with autism spectrum disorders
      participated in the study. Outcome measures were Quality of Life Inventory, Sense
      of Coherence Scale, Rosenberg Self-Esteem Scale and an exploratory analysis on
      measures of psychiatric health. Participants in both treatment conditions
      reported an increased quality of life at post-treatment (d = 0.39, p < 0.001),
      with no difference between interventions. No amelioration of psychiatric symptoms
      was observed. The dropout rate was lower with cognitive behavioural therapy than
      with recreational activity, and participants in cognitive behavioural therapy
      rated themselves as more generally improved, as well as more improved regarding
      expression of needs and understanding of difficulties. Both interventions appear
      to be promising treatment options for adults with autism spectrum disorder. The
      interventions' similar efficacy may be due to the common elements, structure and
      group setting. Cognitive behavioural therapy may be additionally beneficial in
      terms of increasing specific skills and minimizing dropout.

PMID- 24089424
TI  - Course of bereavement over 8-10 years in first degree relatives and spouses of
      people who committed suicide: longitudinal community based cohort study.
AB  - OBJECTIVE: To identify factors predicting the long term course of complicated
      grief, depression, and suicide ideation in a community based sample of relatives
      bereaved through suicide. DESIGN: Longitudinal cohort study. Included in the
      multilevel regression models were sociodemographic and personality features,
      mental health history, records of received help, long term complicated grief,
      depression, and suicide ideation. SETTING: Community based sample located in the
      northern part of the Netherlands. PARTICIPANTS: 153 first degree relatives and
      spouses of 74 people who had committed suicide. MAIN OUTCOME MEASURES:
      Complicated grief, depression, and suicide ideation assessed at 2.5 months, 13
      months and 96-120 months (8-10 years) by means of self report questionnaires.
      RESULTS: Complicated grief, depression, and suicide ideation were mutually
      associated in relatives and spouses of people who had committed suicide. A
      history of attempted suicide was associated with long term suicide ideation (odds
      ratio 5.5, 95% confidence interval 1.8 to 16.7; P=0.003). Depression was more
      likely to be predicted by female sex and low mastery, whereas complicated grief
      was more likely to be predicted by the trauma of losing a child. The risk of both
      complicated grief and depression decreased over time; for complicated grief the
      change corresponded with a Cohen's d effect size of 0.36 at 13 months and 0.89 at
      96-120 months; for depression these figures were 0.28 at 13 months and 0.94 at 96
      120 months. The long term course of bereavement was not affected by family based
      cognitive behavioural therapy, support from a general practitioner, and/or mental
      healthcare. Mutual support was associated with an increased risk of complicated
      grief: B regression coefficient=6.4 (95% confidence interval 1.8 to 11.0;
      P=0.006). Throughout this long term study, selection bias might have affected
      some outcomes. CONCLUSION: In relatives bereaved by suicide, suicide ideation is
      associated with an increased risk of long term complicated grief and depression.
      The risk of complicated grief and depression decreases over time. Although mutual
      support is associated with an increased risk of complicated grief, we could not
      draw conclusions about a causal relation.

PMID- 24089425
TI  - Flying a desk.

PMID- 24089426
TI  - Healthcare staff must properly introduce themselves to patients.

PMID- 24089427
TI  - Where's the evidence for NHS health checks?

PMID- 24089428
TI  - The art of deception.

PMID- 24089429
TI  - Childhood obesity is linked to weight gain during pregnancy, US study finds.

PMID- 24089430
TI  - Private insurance website is forced to drop advertisement.

PMID- 24089431
TI  - Most uninsured Americans plan to buy insurance in response to health reform law.

PMID- 24089432
TI  - Identification of transcription factors involved in rice secondary cell wall
      formation.
AB  - Using co-expression network analysis, we identified 123 transcription factors
      (TFs) as candidate secondary cell wall regulators in rice. To validate whether
      these TFs are associated with secondary cell wall formation, six TF genes
      belonging to the MYB, NAC or homeodomain-containing TF families were
      overexpressed or downregulated in rice. With the exception of OsMYB58/63-RNAi
      plants, all transgenic plants showed phenotypes possibly related to secondary
      cell wall alteration, such as dwarfism, narrow and dark green leaves, and also
      altered rice cinnamyl alcohol dehydrogenase 2 (OsCAD2) gene expression and lignin
      content. These results suggest that many of the 123 candidate secondary cell wall
      regulating TFs are likely to function in secondary cell wall formation in rice.
      Further analyses were performed for the OsMYB55/61 and OsBLH6 TFs, the former
      being a TF in which the Arabidopsis ortholog is known to participate in lignin
      biosynthesis (AtMYB61) and the latter being one for which no previous involvement
      in cell wall formation has been reported even in Arabidopsis (BLH6). OsMYB55/61
      and OsBLH6-GFP fusion proteins localized to the nucleus of onion epidermal cells.
      Moreover, expression of a reporter gene driven by the OsCAD2 promoter was
      enhanced in rice calli when OsMYB55/61 or OsBLH6 was transiently expressed,
      demonstrating that they function in secondary cell wall formation. These results
      show the validity of identifying potential secondary cell wall TFs in rice by the
      use of rice co-expression network analysis. 

PMID- 24089433
TI  - Survey of genes involved in rice secondary cell wall formation through a co
      expression network.
AB  - The plant secondary cell wall is the major source of lignocellulosic biomass, a
      renewable energy resource that can be used for bioethanol production. To
      comprehensively identify transcription factors (TFs), glycosyltransferase (GT)
      and glycosyl hydrolase (GH) involved in secondary cell wall formation in rice
      (Oryza sativa), co-expression network analysis was performed using 68 microarray
      data points for different rice tissues and stages. In addition to rice genes
      encoding orthologs of Arabidopsis thaliana TFs known to regulate secondary cell
      wall formation, the network analysis suggested many novel TF genes likely to be
      involved in cell wall formation. In the accompanying paper (Hirano et al.),
      several of these TFs are shown to be involved in rice secondary cell wall
      formation. Based on a comparison of the rice and Arabidopsis networks, TFs were
      classified as common to both species or specific to each plant species,
      suggesting that in addition to a common transcriptional regulatory mechanism of
      cell wall formation, the two plants may also use species-specific groups of TFs
      during secondary wall formation. Similarly, genes encoding GT and GH were also
      classified as genes showing species-common or species-specific expression
      patterns. In addition, genes for primary or secondary cell wall formation were
      also suggested. The list of rice TF, GT and GH genes provides an opportunity to
      unveil the regulation of secondary cell wall formation in grasses, leading to
      optimization of the cell wall for biofuel production. 

PMID- 24089434
TI  - The effects of action observational training on walking ability in chronic stroke
      patients: a double-blind randomized controlled trial.
AB  - OBJECTIVE: To investigate the effect of action observational training on walking
      ability with chronic stroke patients. DESIGN: A double-blind randomized
      controlled trial. SETTING: Inpatient rehabilitation hospital. PARTICIPANTS:
      Thirty chronic stroke patients. INTERVENTIONS: Patients in both groups underwent
      treadmill training for 30 minutes. The action observational training group (n =
      15) watched a video of treadmill walking actions taken at various speeds before
      treadmill training for 10 minutes. The control group (n = 15) watched a nature
      video unrelated to gait training for the same amount of time. All participants
      received training five times a week for a period of four weeks. MAIN MEASURES:
      Timed up and go test, 10-metre walk test, 6-minute walk test and maximal flexed
      knee angle in the swing phase during walking. RESULTS: There were significant
      improvements in timed up and go test (-4.47 vs. -2.47 seconds), 10-m walk test
      (0.35 vs. 0.16 m/s), 6-minute walk test (93.13 vs. 32.53 m) and maximal flexed
      knee angle in the swing phase during walking (7.11 vs. 4.58 degrees) in the
      action observational training group compared with the control group (P < 0.05).
      Small to huge effect sizes of 1.27, 0.57, 2.34 and 0.37 were observed for timed
      up and go test, 10-m walk test, 6-minute walk test, and maximal flexed knee angle
      in the swing phase during walking, respectively. CONCLUSION: These results
      suggest that action observational training is an effective method for improvement
      of the walking ability in chronic stroke patients.

PMID- 24089435
TI  - A reevaluation of the role of Arabidopsis NRT1.1 in high-affinity nitrate
      transport.

PMID- 24089436
TI  - The gene sml0013 of Synechocystis species strain PCC 6803 encodes for a novel
      subunit of the NAD(P)H oxidoreductase or complex I that is ubiquitously
      distributed among Cyanobacteria.
AB  - The NAD(P)H oxidoreductase or complex I (NDH1) complex participates in many
      processes such as respiration, cyclic electron flow, and inorganic carbon
      concentration in the cyanobacterial cell. Despite immense progress in our
      understanding of the structure-function relation of the cyanobacterial NDH1
      complex, the subunits catalyzing NAD(P)H docking and oxidation are still missing.
      The gene sml0013 of Synechocystis 6803 encodes for a small protein of unknown
      function for which homologs exist in all completely known cyanobacterial genomes.
      The protein exhibits weak similarities to the NDH-dependent flow6 (NDF6) protein,
      which was reported from Arabidopsis (Arabidopsis thaliana) chloroplasts as a NDH
      subunit. An sml0013 inactivation mutant of Synechocystis 6803 was generated and
      characterized. It showed only weak differences regarding growth and pigmentation
      in various culture conditions; most remarkably, it exhibited a glucose-sensitive
      phenotype in the light. The genome-wide expression pattern of the
      Deltasml0013::Km mutant was almost identical to the wild type when grown under
      high CO2 conditions as well as after shifts to low CO2 conditions. However,
      measurements of the photosystem I redox kinetic in cells of the Deltasml0013::Km
      mutant revealed differences, such as a decreased capability of cyclic electron
      flow as well as electron flow into respiration in comparison with the wild type.
      These results suggest that the Sml0013 protein (named NdhP) represents a novel
      subunit of the cyanobacterial NDH1 complex, mediating its coupling either to the
      respiratory or the photosynthetic electron flow. 

PMID- 24089439
TI  - New strategies in endometrial cancer: targeting the PI3K/mTOR pathway--the devil
      is in the details.
AB  - Endometrial cancer is the most common gynecologic malignancy in the developed
      world and affects approximately 40,000 women in the United States each year. The
      phosphoinositide 3-kinase (PI3K) signaling pathway regulates key aspects of
      cancer biology including glucose uptake and metabolism, cellular growth, and
      survival. Endometrial cancers harbor the highest rates of PI3K pathway
      alterations reported to date. The PI3K pathway is highly druggable and several
      classes of agents are in clinical development including rapalogs, pan-PI3K
      inhibitors, PI3K isoform-specific inhibitors, dual PI3K/mTOR catalytic
      inhibitors, mTOR-specific catalytic inhibitors, and AKT inhibitors. It has been
      10 years since the initiation of the first studies of rapalogs as anticancer
      agents. There are more than 20 registered clinical trials of PI3K/mTOR inhibitors
      as single agents or in therapeutic combinations for the treatment of endometrial
      cancers. What have we learned from the completed studies? What can we expect to
      learn from ongoing studies? What should we anticipate moving forward? Clin Cancer
      Res; 19(19); 5264-74. (c)2013 AACR. 

PMID- 24089440
TI  - A sea change in melanoma.

PMID- 24089437
TI  - Maize LAZY1 mediates shoot gravitropism and inflorescence development through
      regulating auxin transport, auxin signaling, and light response.
AB  - Auxin is a plant hormone that plays key roles in both shoot gravitropism and
      inflorescence development. However, these two processes appear to be parallel and
      to be regulated by distinct players. Here, we report that the maize (Zea mays)
      prostrate stem1 mutant, which is allelic to the classic mutant lazy plant1 (la1),
      displays prostrate growth with reduced shoot gravitropism and defective
      inflorescence development. Map-based cloning identified maize ZmLA1 as the
      functional ortholog of LAZY1 in rice (Oryza sativa) and Arabidopsis (Arabidopsis
      thaliana). It has a unique role in inflorescence development and displays
      enriched expression in reproductive organs such as tassels and ears.
      Transcription of ZmLA1 responds to auxin and is repressed by light. Furthermore,
      ZmLA1 physically interacts with a putative auxin transport regulator in the
      plasma membrane and a putative auxin signaling protein in the nucleus. RNA-SEQ
      data showed that dozens of auxin transport, auxin response, and light signaling
      genes were differentially expressed in la1 mutant stems. Therefore, ZmLA1 might
      mediate the cross talk between shoot gravitropism and inflorescence development
      by regulating auxin transport, auxin signaling, and probably light response in
      maize.

PMID- 24089441
TI  - The intersection of immune-directed and molecularly targeted therapy in advanced
      melanoma: where we have been, are, and will be.
AB  - In three years, four drugs have gained regulatory approval for the treatment of
      metastatic and unresectable melanoma, with at least seven other drugs having
      recently completed, currently in, or soon to be in phase III clinical testing.
      This amazing achievement has been made following a remarkable increase of
      knowledge in molecular biology and immunology that led to the identification of
      high-valued therapeutic targets and the clinical development of agents that
      effectively engage and inhibit these targets. The discovery of either effective
      molecularly targeted therapies or immunotherapies would have led to dramatic
      improvements to the standard-of-care treatment of melanoma. However, through
      parallel efforts that have showcased the efficacy of small-molecule BRAF and MAP
      ERK kinase (MEK) inhibitors, as well as the immune checkpoint inhibitors, namely
      ipilimumab and the anti-PD1/PDL1 antibodies (lambrolizumab, nivolumab, MPDL3280),
      an opportunity exists to transform the treatment of melanoma specifically and
      cancer generally by exploring rational combinations of molecularly targeted
      therapies, immunotherapies, and molecular targeted therapies with
      immunotherapies. This overview presents the historical context to this
      therapeutic revolution, reviews the benefits and limitations of current
      therapies, and provides a look ahead at where the field is headed.

PMID- 24089442
TI  - Adoptive T-cell transfer therapy and oncogene-targeted therapy for melanoma: the
      search for synergy.
AB  - The clinical strengths of immunotherapy and small-molecule inhibitors targeting
      the mitogen-activated protein kinase (MAPK) pathway appear to be largely
      complementary for the treatment of advanced melanoma. In current practice, most
      patients with BRAF V600 mutant melanomas will see both modalities. Several in
      vitro and in vivo studies suggest that combining immunotherapy with MAPK
      inhibition may have synergistic effects. First, mouse models show that adoptive
      cell therapy (ACT) can be enhanced by vaccination. Rapid tumor destruction by
      vemurafenib could provide a vaccine-like stimulus to adoptively transferred T
      cells. Second, both in mice and in early clinical trials, melanoma metastases
      treated with MAPK inhibitors seem to display increased T-cell infiltrates. Third,
      MAPK inhibition upregulates the expression of some melanoma antigens and,
      therefore, may enhance T-cell recognition of vemurafenib-treated melanomas.
      Fourth, vemurafenib may sensitize tumor cells to immune destruction. Finally,
      some investigators have found that an optimal antitumor effect from MAPK
      inhibition is dependent on an intact host immune response. Currently, the Surgery
      Branch of the National Cancer Institute has initiated a phase II trial combining
      the BRAF inhibitor vemurafenib with ACT using tumor-infiltrating lymphocytes in
      patients with BRAF-mutant tumors to investigate the safety and efficacy of this
      combination. The proposed mechanisms for synergy between these two modalities can
      be complex, and their optimal combination may require testing a variety of
      sequences and schedules.

PMID- 24089443
TI  - CTLA-4 and PD-1/PD-L1 blockade: new immunotherapeutic modalities with durable
      clinical benefit in melanoma patients.
AB  - Immune checkpoint blockade with monoclonal antibodies directed at the inhibitory
      immune receptors CTLA-4, PD-1, and PD-L1 has emerged as a successful treatment
      approach for patients with advanced melanoma. Ipilimumab is the first agent
      associated with a documented improved overall survival benefit in this patient
      population. A striking attribute of CTLA-4 blockade is the durability of
      objective responses, leading to speculation of a possible cure for some patients.
      Many tumor responses achieved with PD-1 and PD-L1 inhibition were durable in the
      phase I trials and were seen in a higher proportion of patients with melanoma
      than typically observed with ipilimumab. Biomarker development to identify the
      subset of patients with melanoma who will achieve durable clinical benefit with
      checkpoint blockade is critical; tumor PD-L1 expression has been promising in
      early studies. The contrast between unprecedented response rates but limited
      durability of responses achieved with BRAF and MEK inhibition in BRAF(V600)
      mutated melanoma and the impressive durability but relatively low rate of
      response achieved with immune checkpoint blockade is striking. Preclinical data
      on potential synergies between CTLA-4/PD-1/PD-L1 inhibition and MAPK-targeted
      therapy is emerging, and combined immune checkpoint blockade and MAPK inhibition
      are being explored in clinical trials. Other promising approaches to increase the
      number of patients with melanoma who benefit from durable responses with immune
      checkpoint blockade include concurrent or sequenced CTLA-4 and PD-1/PD-L1
      inhibition and combination with other immunotherapeutic strategies. Clin Cancer
      Res; 19(19); 5300-9. (c)2013 AACR. 

PMID- 24089445
TI  - The cell-cycle regulator CDK4: an emerging therapeutic target in melanoma.
AB  - The recent clinical success of targeted therapies in melanoma directed at the
      oncogene BRAF validates the concept of targeting oncogenes. The p16-cyclin D
      CDK4/6-retinoblastoma protein pathway (CDK4 pathway) is dysregulated in 90% of
      melanomas, and is, therefore, an obvious therapeutic target for this disease. The
      main outcome of CDK4 activation is the phosphorylation and, thus, inhibition of
      the retinoblastoma protein leading to G1-S cell-cycle transition. In addition,
      CDK4 directly phosphorylates other proteins that promote cell-cycle progression
      and inhibit both cell senescence and apoptosis. In preclinical studies, the
      response to CDK4 inhibition correlates with genomic changes that increase CDK4
      activity, most notably where the tumor suppressor CDKN2A (p16(INK4A)) is deleted.
      A central question is whether melanomas with activating events in the CDK4
      pathway have become "addicted" to this signaling pathway, in which case
      inhibition of CDK4 would not simply induce cell-cycle arrest but induce cell
      death and tumor regression. Recently, a number of selective CDK4/6 inhibitors
      have entered clinical trials, and these compounds are showing great promise in
      that they are well tolerated and show clinical benefit. This review discusses the
      CDK4 pathway, its dysregulation in melanoma, the consequences of CDK4 pathway
      inhibition, and potential novel combinational strategies for the treatment of
      melanoma.

PMID- 24089444
TI  - Navigating the therapeutic complexity of PI3K pathway inhibition in melanoma.
AB  - Melanoma is entering into an era of combinatorial approaches to build upon recent
      clinical breakthroughs achieved by novel single-agent therapies. One of the
      leading targets to emerge from the growing understanding of the molecular
      pathogenesis, heterogeneity, and resistance mechanisms of melanomas is the
      phosphoinositide 3-kinase (PI3K)-AKT pathway. Multiple genetic and epigenetic
      aberrations that activate this pathway have been identified in melanomas de novo
      and in acquired resistance models. These developments have been paralleled by the
      establishment of models for preclinical testing and the availability of compounds
      that target various effectors in the pathway. Thus, in addition to having a
      strong rationale for targeting, the PI3K-AKT pathway presents an immediate
      clinical opportunity. However, the development of effective strategies against
      this pathway must overcome several key challenges, including optimizing patient
      selection, overcoming feedback loops, and pathway cross-talk that can mediate
      resistance. This review discusses the current understanding and ongoing research
      about the PI3K-AKT pathway in melanoma and emerging strategies to achieve
      clinical benefit in patients by targeting it.

PMID- 24089446
TI  - Weekly nab-Rapamycin in patients with advanced nonhematologic malignancies: final
      results of a phase I trial.
AB  - PURPOSE: This dose-finding phase I study investigated the maximum-tolerated dose
      (MTD) and safety of weekly nanoparticle albumin-bound rapamycin (nab-rapamycin)
      in patients with untreatable advanced nonhematologic malignancies. EXPERIMENTAL
      DESIGN: nab-Rapamycin was administered weekly for 3 weeks followed by 1 week of
      rest, with a starting dose of 45 mg/m(2). Additional doses were 56.25, 100, 150,
      and 125 mg/m(2). RESULTS: Of 27 enrolled patients, 26 were treated. Two dose
      limiting toxicities (DLT) occurred at 150 mg/m(2) [grade 3 aspartate
      aminotransferase (AST) elevation and grade 4 thrombocytopenia], and two DLTs
      occurred at 125 mg/m(2) (grade 3 suicidal ideation and grade 3 hypophosphatemia).
      Thus, the MTD was declared at 100 mg/m(2). Most treatment-related adverse events
      (TRAE) were grade 1/2, including thrombocytopenia (58%), hypokalemia (23%),
      mucositis (38%), fatigue (27%), rash (23%), diarrhea (23%), nausea (19%), anemia
      (19%), hypophosphatemia (19%), neutropenia (15%), and hypertriglyceridemia (15%).
      Only one grade 3 nonhematologic TRAE (dyspnea) and one grade 3 hematologic event
      (anemia) occurred at the MTD. One patient with kidney cancer had a partial
      response and 2 patients remained on study for 365 days (patient with
      mesothelioma) and 238 days (patient with neuroendocrine tumor). The peak
      concentration (Cmax) and area under the concentration-time curve (AUC) of
      rapamycin increased with dose between 45 and 150 mg/m(2), except for a relatively
      low AUC at 125 mg/m(2). nab-Rapamycin significantly inhibited mTOR targets S6K
      and 4EBP1. CONCLUSIONS: The clinical dose of single-agent nab-rapamycin was
      established at 100 mg/m(2) weekly (3 of 4 weeks) given intravenously, which was
      well tolerated with preliminary evidence of response and stable disease, and
      produced a fairly dose-proportional pharmacokinetic profile in patients with
      unresectable advanced nonhematologic malignancies.

PMID- 24089448
TI  - Positional information, in bits.
AB  - Cells in a developing embryo have no direct way of "measuring" their physical
      position. Through a variety of processes, however, the expression levels of
      multiple genes come to be correlated with position, and these expression levels
      thus form a code for "positional information." We show how to measure this
      information, in bits, using the gap genes in the Drosophila embryo as an example.
      Individual genes carry nearly two bits of information, twice as much as would be
      expected if the expression patterns consisted only of on/off domains separated by
      sharp boundaries. Taken together, four gap genes carry enough information to
      define a cell's location with an error bar of ~1 along the anterior/posterior
      axis of the embryo. This precision is nearly enough for each cell to have a
      unique identity, which is the maximum information the system can use, and is
      nearly constant along the length of the embryo. We argue that this constancy is a
      signature of optimality in the transmission of information from primary morphogen
      inputs to the output of the gap gene network.

PMID- 24089450
TI  - Liver type I regulatory T cells suppress germinal center formation in HBV
      tolerant mice.
AB  - The liver plays a critical role in inducing systemic immune tolerance, for
      example, during limiting hypersensitivity to food allergy and in rendering
      acceptance of allotransplant or even hepatotropic pathogens. We investigated the
      unknown mechanisms of liver tolerance by using an established hepatitis B virus
      (HBV)-carrier mouse model, and found that these mice exhibited an antigen
      specific tolerance toward peripheral HBsAg vaccination, showing unenlarged
      draining lymph node (DLN), lower number of germinal centers (GC), and
      inactivation of GC B cells and follicular T helper (Tfh) cells. Both in vivo and
      in vitro immune responses toward HBsAg were suppressed by mononuclear cells from
      HBV-carrier mice, which were CD4(+) Foxp3(-) type 1 regulatory T (Tr1)-like cells
      producing IL-10. Using recipient Rag1(-/-) mice, hepatic Tr1-like cells from day
      7 of HBV-persistent mice acquired the ability to inhibit anti-HBV immunity 3 d
      earlier than splenic Tr1-like cells, implying that hepatic Tr1-like cells were
      generated before those in spleen. Kupffer cell depletion or IL-10 deficiency led
      to impairment of Tr1-like cell generation, along with breaking HBV persistence.
      The purified EGFP(+)CD4(+) T cells (containing Tr1-like cells) from HBV-carrier
      mice trafficked in higher numbers to DLN in recipient mice after HBsAg
      vaccination, and subsequently inactivated both Tfh cells and GC B cells via
      secreting IL-10, resulting in impaired GC formation and anti-HB antibody
      production. Thus, our results indicate Tr1-like cells migrate from the liver to
      the DLN and inhibit peripheral anti-HBV immunity by negatively regulating GC B
      cells and Tfh cells. 

PMID- 24089452
TI  - The Chobot site (Alberta, Canada) cannot provide evidence of a cosmic impact
      12,800 y ago.

PMID- 24089451
TI  - Kindlin-3 regulates integrin activation and adhesion reinforcement of effector T
      cells.
AB  - Activated T cells use very late antigen-4/alpha4beta1 integrin for capture,
      rolling on, and firm adhesion to endothelial cells, and use leukocyte function
      associated antigen-1/alphaLbeta2 integrin for subsequent crawling and
      extravasation. Inhibition of alpha4beta1 is sufficient to prevent extravasation
      of activated T cells and is successfully used to combat autoimmune diseases, such
      as multiple sclerosis. Here we show that effector T cells lacking the integrin
      activator Kindlin-3 extravasate and induce experimental autoimmune
      encephalomyelitis in mice immunized with autoantigen. In sharp contrast,
      adoptively transferred autoreactive T cells from Kindlin-3-deficient mice fail to
      extravasate into the naive CNS. Mechanistically, autoreactive Kindlin-3-null T
      cells extravasate when the CNS is inflamed and the brain microvasculature
      expresses high levels of integrin ligands. Flow chamber assays under
      physiological shear conditions confirmed that Kindlin-3-null effector T cells
      adhere to high concentrations of vascular cell adhesion molecule-1 and
      intercellular adhesion molecule-1, albeit less efficiently than WT T cells.
      Although these arrested T cells polarize and start crawling, only few remain
      firmly adherent over time. Our data demonstrate that the requirement of Kindlin-3
      for effector T cells to induce alpha4beta1 and alphaLbeta2 integrin ligand
      binding and stabilization of integrin-ligand bonds is critical when integrin
      ligand levels are low, but of less importance when integrin ligand levels are
      high. 

PMID- 24089449
TI  - CACTA-like transposable element in ZmCCT attenuated photoperiod sensitivity and
      accelerated the postdomestication spread of maize.
AB  - The postdomestication adaptation of maize to longer days required reduced
      photoperiod sensitivity to optimize flowering time. We performed a genome-wide
      association study and confirmed that ZmCCT, encoding a CCT domain-containing
      protein, is associated with the photoperiod response. In early-flowering maize we
      detected a CACTA-like transposable element (TE) within the ZmCCT promoter that
      dramatically reduced flowering time. TE insertion likely occurred after
      domestication and was selected as maize adapted to temperate zones. This process
      resulted in a strong selective sweep within the TE-related block of linkage
      disequilibrium. Functional validations indicated that the TE represses ZmCCT
      expression to reduce photoperiod sensitivity, thus accelerating maize spread to
      long-day environments. 

PMID- 24089454
TI  - Novel uses for platelet function testing in the clinical laboratory: where are we
      now?

PMID- 24089453
TI  - Novel secreted antigens of Mycobacterium paratuberculosis as serodiagnostic
      biomarkers for Johne's disease in cattle.
AB  - Johne's disease is a chronic gastroenteritis of cattle caused by Mycobacterium
      avium subsp. paratuberculosis that afflicts 40% of dairy herds worldwide. M.
      avium subsp. paratuberculosis-infected cattle can remain asymptomatic for years
      while transmitting the pathogen via fecal contamination and milk. Current
      serodiagnosis with enzyme-linked immunosorbent assays (ELISAs) fails to detect
      asymptomatic M. avium subsp. paratuberculosis-infected cattle due to the use of
      poorly defined antigens and knowledge gaps in our understanding of M. avium
      subsp. paratuberculosis components eliciting pathogen-specific immune responses.
      We set out to (i) define a subset of proteins that contain putative antigenic
      targets and (ii) screen these antigen pools for immunogens relevant in detecting
      infection. To accomplish our first objective, we captured and resolved M. avium
      subsp. paratuberculosis-secreted proteins using a 2-step fractionation method and
      reverse-phase liquid chromatography to identify 162 unique proteins, of which 66
      had not been previously observed in M. avium subsp. paratuberculosis culture
      filtrates. Subsequent screening of M. avium subsp. paratuberculosis-secreted
      proteins showed four antigens, of which one or more reacted on immunoblotting
      with individual serum samples from 35 M. avium subsp. paratuberculosis-infected
      cows. Moreover, these novel antigens reacted with sera from 6 low M. avium subsp.
      paratuberculosis shedders and 3 fecal-culture-positive cows labeled as ELISA
      seronegative. The specificity of these antigens was demonstrated using negative
      control sera from uninfected calves (n = 5) and uninfected cows (n = 5), which
      did not react to any of these antigens in immunoblotting. As three of the four
      antigens are novel, their characterization and incorporation into an ELISA-based
      format will aid in detecting asymptomatic cattle in early or subclinical stages
      of disease.

PMID- 24089455
TI  - The ethical implications of preimplantation genetic diagnosis.

PMID- 24089456
TI  - Nencki Genomics Database--Ensembl funcgen enhanced with intersections, user data
      and genome-wide TFBS motifs.
AB  - We present the Nencki Genomics Database, which extends the functionality of
      Ensembl Regulatory Build (funcgen) for the three species: human, mouse and rat.
      The key enhancements over Ensembl funcgen include the following: (i) a user can
      add private data, analyze them alongside the public data and manage access
      rights; (ii) inside the database, we provide efficient procedures for computing
      intersections between regulatory features and for mapping them to the genes. To
      Ensembl funcgen-derived data, which include data from ENCODE, we add information
      on conserved non-coding (putative regulatory) sequences, and on genome-wide
      occurrence of transcription factor binding site motifs from the current versions
      of two major motif libraries, namely, Jaspar and Transfac. The intersections and
      mapping to the genes are pre-computed for the public data, and the result of any
      procedure run on the data added by the users is stored back into the database,
      thus incrementally increasing the body of pre-computed data. As the Ensembl
      funcgen schema for the rat is currently not populated, our database is the first
      database of regulatory features for this frequently used laboratory animal. The
      database is accessible without registration using the mysql client: mysql -h
      database.nencki-genomics.org -u public. Registration is required only to add or
      access private data. A WSDL webservice provides access to the database from any
      SOAP client, including the Taverna Workbench with a graphical user interface.

PMID- 24089457
TI  - Seropositivity to Helicobacter pylori and risk of pancreatic cancer.
AB  - Helicobacter pylori (H. pylori) seropositivity has been inconsistently associated
      with pancreatic cancer. We, therefore, investigated the association between H.
      pylori seropositivity and pancreatic cancer in a case-control study nested within
      Alpha-Tocopherol, Beta-Carotene Cancer Prevention Study (ATBC) cohort of Finnish
      male smokers. Pancreatic cancer cases (n = 353) and control subjects (n = 353)
      were matched on date of baseline serum collection, age at randomization, and
      follow-up time (up to 23.9 years). We used a multiplex serology assay to
      determine the sero-status of antibodies against 15 H. pylori-specific antigens in
      fasting serum samples. Conditional logistic regression was used to calculate the
      odds ratio (OR) and 95% confidence intervals (CI). Neither targeted H. pylori
      antigens in serum nor the combination of all was associated with development of
      pancreatic cancer (combination of all: OR, 0.85; 95% CI, 0.49-1.49). Our results
      suggest that H. pylori is not a risk factor for pancreatic cancer.

PMID- 24089458
TI  - Identification of breast cancer DNA methylation markers optimized for fine-needle
      aspiration samples.
AB  - BACKGROUND: Random periareolar fine-needle aspiration (RP-FNA) is increasingly
      used in trials of breast cancer prevention for biomarker assessments. DNA
      methylation markers may have value as surrogate endpoint biomarkers, but this
      requires identification of biologically relevant markers suitable for
      paucicellular, lymphocyte-contaminated clinical samples. METHODS: Unbiased whole
      genome 5-aza-2'-deoxycytidine (5AZA)-induced gene expression assays, followed by
      several phases of qualitative and quantitative methylation-specific PCR (MSP)
      testing, were used to identify novel breast cancer DNA methylation markers
      optimized for clinical FNA samples. RESULTS: The initial 5AZA experiment
      identified 453 genes whose expression was potentially regulated by promoter
      region methylation. Informatics filters excluded 273 genes unlikely to yield
      useful DNA methylation markers. MSP assays were designed for 271 of the remaining
      genes and, ultimately, 33 genes were identified that were differentially
      methylated in clinical breast cancer samples, as compared with benign RP-FNA
      samples, and never methylated in lymphocytes. A subset of these markers was
      validated by quantitative multiplex MSP in extended clinical sample sets. Using a
      novel permutation method for analysis of quantitative methylation data, PSAT1,
      GNE, CPNE8, and CXCL14 were found to correlate strongly with specific clinical
      and pathologic features of breast cancer. In general, our approach identified
      markers methylated in a smaller subpopulation of tumor cells than those
      identified in published methylation array studies. CONCLUSIONS: Clinically
      relevant DNA methylation markers were identified using a 5AZA-induced gene
      expression approach. IMPACT: These breast cancer-relevant, FNA-optimized DNA
      methylation markers may have value as surrogate endpoint biomarkers in RP-FNA
      studies.

PMID- 24089459
TI  - Childhood height and birth weight in relation to future prostate cancer risk: a
      cohort study based on the copenhagen school health records register.
AB  - BACKGROUND: Adult height has been positively associated with prostate cancer
      risk. However, the exposure window of importance is currently unknown and
      assessments of height during earlier growth periods are scarce. In addition, the
      association between birth weight and prostate cancer remains undetermined. We
      assessed these relationships in a cohort of the Copenhagen School Health Records
      Register (CSHRR). METHODS: The CSHRR comprises 372,636 school children. For boys
      born between the 1930s and 1969, birth weight and annual childhood heights
      measured between ages 7 and 13 years-were analyzed in relation to prostate cancer
      risk. Cox proportional hazards regression models were used to estimate hazard
      ratios (HRs) and 95% confidence intervals (CI). RESULTS: There were 125,211 males
      for analysis, 2,987 of who were subsequently diagnosed with prostate cancer
      during 2.57 million person-years of follow-up. Height z-score was significantly
      associated with prostate cancer risk at all ages (HRs, 1.13 to 1.14). Height at
      age 13 years was more important than height change (P = 0.024) and height at age
      7 years (P = 0.024), when estimates from mutually adjusted models were compared.
      Adjustment of birth weight did not alter the estimates. Birth weight was not
      associated with prostate cancer risk. CONCLUSIONS: The association between
      childhood height and prostate cancer risk was driven by height at age 13 years.
      IMPACT: Our findings implicate late childhood, adolescence, and adulthood growth
      periods as containing the exposure window(s) of interest that underlies the
      association between height and prostate cancer. The causal factor may not be
      singular given the complexity of both human growth and carcinogenesis.

PMID- 24089460
TI  - Predicting risk of bladder cancer using clinical and demographic information from
      prostate, lung, colorectal, and ovarian cancer screening trial participants.
AB  - BACKGROUND: Effective screening and prevention strategies for bladder cancer
      require accurate risk stratification models. We developed models to predict the
      risk of bladder cancer based on clinical and sociodemographic data on
      participants in the Prostate, Lung, Colorectal, and Ovarian Cancer (PLCO)
      screening trial. METHODS: Baseline clinical and sociodemographic data were
      obtained from 149,542 PLCO participants, ages 55 to 74 years, without a prior
      history of bladder cancer. Cox proportional hazards models were used to predict
      the risk of all bladder cancers (ABC) and of high-grade bladder cancers (HGBC)
      from baseline information. We used the HGBC risk model to design a hypothetical
      bladder cancer mortality prevention trial. RESULTS: Over a median follow-up of 12
      years, 1,124 men and 259 women developed bladder cancer (including 392 and 72
      with HGBC, respectively). The incidence in men and in women was 133.6 and 29.6
      cases per 100,000 person-years, respectively. Nomograms constructed for
      predicting the risk of ABC and HGBC had c-indices of 0.746 and 0.759,
      respectively. Age, race, education, smoking (intensity and duration),
      comorbidity, prostatitis, syphilis, and hormone replacement therapy use were
      statistically significant predictors in the models. We show that our risk model
      can be used to design a bladder cancer mortality prevention trial half the size
      of a trial designed without risk stratification. CONCLUSION: Models to predict
      the risk of ABC and HGBC have been developed and validated. IMPACT: Using the
      upper 40th percentile from the HGBC model, a suitable cohort for a screening or
      chemoprevention trial could be identified, although the size and follow-up of
      such a trial would be costly.

PMID- 24089461
TI  - Preclinical evaluation of biopolymer-delivered circulating angiogenic cells in a
      swine model of hibernating myocardium.
AB  - BACKGROUND: Vasculogenic cell-based therapy combined with tissue engineering is a
      promising revascularization approach targeted at patients with advanced coronary
      artery disease, many of whom exhibit myocardial hibernation. However, to date, no
      experimental data have been available in this context; we therefore examined the
      biopolymer-supported delivery of circulating angiogenic cells using a clinically
      relevant swine model of hibernating myocardium. METHODS AND RESULTS: Twenty-five
      swine underwent placement of an ameroid constrictor on the left circumflex
      artery. After 2 weeks, animals underwent echocardiography, rest and stress
      ammonia-positron emission tomography perfusion, and fluorodeoxyglucose positron
      emission tomography viability scans. The following week, swine were randomized to
      receive intramyocardial injections of PBS control (n=10), circulating angiogenic
      cells (n=8), or circulating angiogenic cells+collagen-based matrix (n=7). The
      imaging protocol was repeated after 7 weeks. Baseline positron emission
      tomography myocardial blood flow and myocardial flow reserve were reduced in the
      left circumflex artery territory (both P<0.001), and hibernation (mismatch) was
      observed. At follow-up, stress myocardial blood flow had increased (P<=0.01) and
      hibernation decreased (P<0.01) in the cells+matrix group only. Microsphere
      measured myocardial blood flow validated the perfusion results. Arteriole density
      and wall motion abnormalities improved in the cells+matrix group. There was also
      a strong trend toward an improvement in ejection fraction (P=0.07). CONCLUSIONS:
      In this preclinical swine model of ischemic and hibernating myocardium, the
      combined delivery of circulating angiogenic cells and a collagen-based matrix
      restored perfusion, reduced hibernation, and improved myocardial wall motion.

PMID- 24089462
TI  - Georges Teissier (1900-1972) and the modern synthesis in France.
AB  - This Perspectives is devoted to the ideas of the French zoologist Georges
      Teissier about the mechanisms of evolution and the relations between micro- and
      macroevolution. Working in an almost universally neo-Lamarckian context in
      France, Teissier was one of the very few Darwinians there at the time of the
      evolutionary synthesis. The general atmosphere of French zoology during the 1920s
      and the 1930s will first be recalled, to understand the specific conditions in
      which Teissier became a zoologist. After a brief overview of his joint work with
      Philippe L'Heritier on the experimental genetics of Drosophila, this article
      describes the ways Teissier, during the 1950s, conceptualized the mechanisms that
      could allow for macroevolutionary transitions. 

PMID- 24089467
TI  - Direct interaction between two actin nucleators is required in Drosophila
      oogenesis.
AB  - Controlled actin assembly is crucial to a wide variety of cellular processes,
      including polarity establishment during early development. The recently
      discovered actin mesh, a structure that traverses the Drosophila oocyte during
      mid-oogenesis, is essential for proper establishment of the major body axes.
      Genetic experiments indicate that at least two proteins, Spire (Spir) and
      Cappuccino (Capu), are required to build this mesh. The spire and cappuccino
      genetic loci were first identified as maternal effect genes in Drosophila.
      Mutation in either locus results in the same phenotypes, including absence of the
      mesh, linking them functionally. Both proteins nucleate actin filaments. Spir and
      Capu also interact directly with each other in vitro, suggesting a novel
      synergistic mode of regulating actin. In order to understand how and why proteins
      with similar biochemical activity would be required in the same biological
      pathway, genetic experiments were designed to test whether a direct interaction
      between Spir and Capu is required during oogenesis. Indeed, data in this study
      indicate that Spir and Capu must interact directly with one another and then
      separate to function properly. Furthermore, these actin regulators are controlled
      by a combination of mechanisms, including interaction with one another,
      functional inhibition and regulation of their protein levels. Finally, this work
      demonstrates for the first time in a multicellular organism that the ability of a
      formin to assemble actin filaments is required for a specific structure. 

PMID- 24089463
TI  - RNA-guided nucleases: a new era for engineering the genomes of model and nonmodel
      organisms.

PMID- 24089468
TI  - Evf2 (Dlx6as) lncRNA regulates ultraconserved enhancer methylation and the
      differential transcriptional control of adjacent genes.
AB  - Several lines of evidence suggest that long non-coding RNA (lncRNA)-dependent
      mechanisms regulate transcription and CpG DNA methylation. Whereas CpG island
      methylation has been studied in detail, the significance of enhancer DNA
      methylation and its relationship with lncRNAs is relatively unexplored. Previous
      experiments proposed that the ultraconserved lncRNA Evf2 represses transcription
      through Dlx6 antisense (Dlx6as) transcription and methyl-CpG binding protein
      (MECP2) recruitment to the Dlx5/6 ultraconserved DNA regulatory enhancer
      (Dlx5/6ei) in embryonic day 13.5 medial ganglionic eminence (E13.5 MGE). Here,
      genetic epistasis experiments show that MECP2 transcriptional repression of Evf2
      and Dlx5, but not Dlx6, occurs through antagonism of DLX1/2 in E13.5 MGE.
      Analysis of E13.5 MGE from mice lacking Evf2 and of partially rescued Evf2
      transgenic mice shows that Evf2 prevents site-specific CpG DNA methylation of
      Dlx5/6ei in trans, without altering Dlx5/6 expression. Dlx1/2 loss increases CpG
      DNA methylation, whereas Mecp2 loss does not affect Dlx5/6ei methylation. Based
      on these studies, we propose a model in which Evf2 inhibits enhancer DNA
      methylation, effectively modulating competition between the DLX1/2 activator and
      MECP2 repressor. Evf2 antisense transcription and Evf2-dependent balanced
      recruitment of activator and repressor proteins enables differential
      transcriptional control of adjacent genes with shared DNA regulatory elements. 

PMID- 24089469
TI  - The G protein-coupled receptor GPRC5B contributes to neurogenesis in the
      developing mouse neocortex.
AB  - Neural progenitor cells in the developing brain give rise to neurons and glia.
      Multiple extrinsic signalling molecules and their cognate membrane receptors have
      been identified to control neural progenitor fate. However, a role for G protein
      coupled receptors in cell fate decisions in the brain remains largely putative.
      Here we show that GPRC5B, which encodes an orphan G protein-coupled receptor, is
      present in the ventricular surface of cortical progenitors in the mouse
      developing neocortex and is required for their neuronal differentiation. GPRC5B
      depleted progenitors fail to adopt a neuronal fate and ultimately become
      astrocytes. Furthermore, GPRC5B-mediated signalling is associated with the proper
      regulation of beta-catenin signalling, a pathway crucial for progenitor fate
      decision. Our study uncovers G protein-coupled receptor signalling in the
      neuronal fate determination of cortical progenitors. 

PMID- 24089470
TI  - Pulse propagation by a capacitive mechanism drives embryonic blood flow.
AB  - Pulsatile flow is a universal feature of the blood circulatory system in
      vertebrates and can lead to diseases when abnormal. In the embryo, blood flow
      forces stimulate vessel remodeling and stem cell proliferation. At these early
      stages, when vessels lack muscle cells, the heart is valveless and the Reynolds
      number (Re) is low, few details are available regarding the mechanisms
      controlling pulses propagation in the developing vascular network. Making use of
      the recent advances in optical-tweezing flow probing approaches, fast imaging and
      elastic-network viscous flow modeling, we investigated the blood-flow mechanics
      in the zebrafish main artery and show how it modifies the heart pumping input to
      the network. The movement of blood cells in the embryonic artery suggests that
      elasticity of the network is an essential factor mediating the flow. Based on
      these observations, we propose a model for embryonic blood flow where arteries
      act like a capacitor in a way that reduces heart effort. These results
      demonstrate that biomechanics is key in controlling early flow propagation and
      argue that intravascular elasticity has a role in determining embryonic vascular
      function. 

PMID- 24089471
TI  - A BMP regulatory network controls ectodermal cell fate decisions at the neural
      plate border.
AB  - During ectodermal patterning the neural crest and preplacodal ectoderm are
      specified in adjacent domains at the neural plate border. BMP signalling is
      required for specification of both tissues, but how it is spatially and
      temporally regulated to achieve this is not understood. Here, using a transgenic
      zebrafish BMP reporter line in conjunction with double-fluorescent in situ
      hybridisation, we show that, at the beginning of neurulation, the ventral-to
      dorsal gradient of BMP activity evolves into two distinct domains at the neural
      plate border: one coinciding with the neural crest and the other abutting the
      epidermis. In between is a region devoid of BMP activity, which is specified as
      the preplacodal ectoderm. We identify the ligands required for these domains of
      BMP activity. We show that the BMP-interacting protein Crossveinless 2 is
      expressed in the BMP activity domains and is under the control of BMP signalling.
      We establish that Crossveinless 2 functions at this time in a positive-feedback
      loop to locally enhance BMP activity, and show that it is required for neural
      crest fate. We further demonstrate that the Distal-less transcription factors
      Dlx3b and Dlx4b, which are expressed in the preplacodal ectoderm, are required
      for the expression of a cell-autonomous BMP inhibitor, Bambi-b, which can explain
      the specific absence of BMP activity in the preplacodal ectoderm. Taken together,
      our data define a BMP regulatory network that controls cell fate decisions at the
      neural plate border. 

PMID- 24089472
TI  - Regeneration of breeding tubercles on zebrafish pectoral fins requires androgens
      and two waves of revascularization.
AB  - Sexually dimorphic breeding tubercles (BTs) are keratinized epidermal structures
      that form clusters on the dorsal surface of the anterior rays of zebrafish male
      pectoral fins. BTs appear during sexual maturation and are maintained through
      regular shedding and renewal of the keratinized surface. Following pectoral fin
      amputation, BT clusters regenerate after the initiation of revascularization, but
      concomitantly with a second wave of angiogenesis. This second wave of
      regeneration forms a web-like blood vessel network that penetrates the supportive
      epidermis of BTs. Upon analyzing the effects of sex steroids and their
      inhibitors, we show that androgens induce and estrogens inhibit BT cluster
      formation in intact and regenerating pectoral fins. Androgen-induced BT formation
      in females is accompanied by the formation of a male-like blood vessel network.
      Treatment of females with both androgens and an angiogenesis inhibitor results in
      the formation of undersized BT clusters when compared with females treated with
      androgens alone. Overall, the growth and regeneration of large BTs requires a
      hormonal stimulus and the presence of an additional blood vessel network that is
      naturally found in males. 

PMID- 24089473
TI  - A systems level predictive model for global gene regulation of methanogenesis in
      a hydrogenotrophic methanogen.
AB  - Methanogens catalyze the critical methane-producing step (called methanogenesis)
      in the anaerobic decomposition of organic matter. Here, we present the first
      predictive model of global gene regulation of methanogenesis in a
      hydrogenotrophic methanogen, Methanococcus maripaludis. We generated a
      comprehensive list of genes (protein-coding and noncoding) for M. maripaludis
      through integrated analysis of the transcriptome structure and a newly
      constructed Peptide Atlas. The environment and gene-regulatory influence network
      (EGRIN) model of the strain was constructed from a compendium of transcriptome
      data that was collected over 58 different steady-state and time-course
      experiments that were performed in chemostats or batch cultures under a spectrum
      of environmental perturbations that modulated methanogenesis. Analyses of the
      EGRIN model have revealed novel components of methanogenesis that included at
      least three additional protein-coding genes of previously unknown function as
      well as one noncoding RNA. We discovered that at least five regulatory mechanisms
      act in a combinatorial scheme to intercoordinate key steps of methanogenesis with
      different processes such as motility, ATP biosynthesis, and carbon assimilation.
      Through a combination of genetic and environmental perturbation experiments we
      have validated the EGRIN-predicted role of two novel transcription factors in the
      regulation of phosphate-dependent repression of formate dehydrogenase-a key
      enzyme in the methanogenesis pathway. The EGRIN model demonstrates regulatory
      affiliations within methanogenesis as well as between methanogenesis and other
      cellular functions. 

PMID- 24089475
TI  - Non-Hebbian long-term potentiation of inhibitory synapses in the thalamus.
AB  - The thalamus integrates and transmits sensory information to the neocortex. The
      activity of thalamocortical relay (TC) cells is modulated by specific inhibitory
      circuits. Although this inhibition plays a crucial role in regulating thalamic
      activity, little is known about long-term changes in synaptic strength at these
      inhibitory synapses. Therefore, we studied long-term plasticity of inhibitory
      inputs to TC cells in the posterior medial nucleus of the thalamus by combining
      patch-clamp recordings with two-photon fluorescence microscopy in rat brain
      slices. We found that specific activity patterns in the postsynaptic TC cell
      induced inhibitory long-term potentiation (iLTP). This iLTP was non-Hebbian
      because it did not depend on the timing between presynaptic and postsynaptic
      activity, but it could be induced by postsynaptic burst activity alone. iLTP
      required postsynaptic dendritic Ca(2+) influx evoked by low-threshold Ca(2+)
      spikes. In contrast, tonic postsynaptic spiking from a depolarized membrane
      potential (-50 mV), which suppressed these low-threshold Ca(2+) spikes, induced
      no plasticity. The postsynaptic dendritic Ca(2+) increase triggered the synthesis
      of nitric oxide that retrogradely activated presynaptic guanylyl cyclase,
      resulting in the presynaptic expression of iLTP. The dependence of iLTP on the
      membrane potential and therefore on the postsynaptic discharge mode suggests that
      this form of iLTP might occur during sleep, when TC cells discharge in bursts.
      Therefore, iLTP might be involved in sleep state-dependent modulation of thalamic
      information processing and thalamic oscillations. 

PMID- 24089474
TI  - Chronic stress induces a selective decrease in AMPA receptor-mediated synaptic
      excitation at hippocampal temporoammonic-CA1 synapses.
AB  - Chronic stress promotes depression, but how it disrupts cognition and mood
      remains unknown. Chronic stress causes atrophy of pyramidal cell dendrites in the
      hippocampus and cortex in human and animal models, and a depressive-like
      behavioral state. We now test the hypothesis that excitatory temporoammonic (TA)
      synapses in the distal dendrites of CA1 pyramidal cells in rats are altered by
      chronic unpredictable stress (CUS) and restored by chronic antidepressant
      treatment, in conjunction with the behavioral consequences of CUS. We observed a
      decrease in AMPAR-mediated excitation at TA-CA1 synapses, but not Schaffer
      collateral-CA1 synapses, after CUS, with a corresponding layer-specific decrease
      in GluA1 expression. Both changes were reversed by chronic fluoxetine. CUS also
      disrupted long-term memory consolidation in the Morris water maze, a function of
      TA-CA1 synapses. The decreases in TA-CA1 AMPAR-mediated excitation and
      performance in the consolidation test were correlated positively with decreases
      in sucrose preference, a measure of anhedonia. We conclude that chronic stress
      selectively decreases AMPAR number and function at specific synapses and suggest
      that this underlies various depressive endophenotypes. Our findings provide
      evidence that glutamatergic dysfunction is an underlying cause of depression and
      that current first-line antidepressant drugs act by restoring excitatory synaptic
      strength. Our findings suggest novel therapeutic targets for this debilitating
      disease. 

PMID- 24089476
TI  - Impaired critical period plasticity in primary auditory cortex of fragile X model
      mice.
AB  - Fragile X syndrome, the most common form of heritable mental retardation, is a
      developmental disorder with known effects within sensory systems. Altered
      developmental plasticity has been reported in the visual and somatosensory
      systems in Fmr1 knock-out (KO) mice. Behavioral studies have revealed maladaptive
      auditory responses in fragile X syndrome patients and Fmr1 KO mice, suggesting
      that adaptive plasticity may also be impaired in the auditory system. Here we
      show that, whereas tonotopic frequency representation develops normally in Fmr1
      KO mice, developmental plasticity in primary auditory cortex is grossly impaired.
      This deficit can be rescued by pharmacological blockade of mGluR5 receptors.
      These results support the mGluR hypothesis of fragile X mental retardation and
      suggest that deficient developmental plasticity may contribute to maladaptive
      auditory processing in fragile X syndrome. 

PMID- 24089478
TI  - Updating expected action outcome in the medial frontal cortex involves an
      evaluation of error type.
AB  - Forming expectations about the outcome of an action is an important prerequisite
      for action control and reinforcement learning in the human brain. The medial
      frontal cortex (MFC) has been shown to play an important role in the
      representation of outcome expectations, particularly when an update of expected
      outcome becomes necessary because an error is detected. However, error detection
      alone is not always sufficient to compute expected outcome because errors can
      occur in various ways and different types of errors may be associated with
      different outcomes. In the present study, we therefore investigate whether
      updating expected outcome in the human MFC is based on an evaluation of error
      type. Our approach was to consider an electrophysiological correlate of MFC
      activity on errors, the error-related negativity (Ne/ERN), in a task in which two
      types of errors could occur. Because the two error types were associated with
      different amounts of monetary loss, updating expected outcomes on error trials
      required an evaluation of error type. Our data revealed a pattern of Ne/ERN
      amplitudes that closely mirrored the amount of monetary loss associated with each
      error type, suggesting that outcome expectations are updated based on an
      evaluation of error type. We propose that this is achieved by a proactive
      evaluation process that anticipates error types by continuously monitoring error
      sources or by dynamically representing possible response-outcome relations. 

PMID- 24089477
TI  - Graded encoding of food odor value in the Drosophila brain.
AB  - Odors are highly evocative, yet how and where in the brain odors derive meaning
      remains unknown. Our analysis of the Drosophila brain extends the role of a small
      number of hunger-sensing neurons to include food-odor value representation. In
      vivo two-photon calcium imaging shows the amplitude of food odor-evoked activity
      in neurons expressing Drosophila neuropeptide F (dNPF), the neuropeptide Y
      homolog, strongly correlates with food-odor attractiveness. Hunger elevates
      neural and behavioral responses to food odors only, although food odors that
      elicit attraction in the fed state also evoke heightened dNPF activity in fed
      flies. Inactivation of a subset of dNPF-expressing neurons or silencing dNPF
      receptors abolishes food-odor attractiveness, whereas genetically enhanced dNPF
      activity not only increases food-odor attractiveness but promotes attraction to
      aversive odors. Varying the amount of presented odor produces matching graded
      neural and behavioral curves, which can function to predict preference between
      odors. We thus demonstrate a possible motivationally scaled neural "value signal"
      accessible from uniquely identifiable cells. 

PMID- 24089479
TI  - Linking redox regulation of NMDAR synaptic function to cognitive decline during
      aging.
AB  - NMDA receptors (NMDARs) play a critical role in learning and memory; however,
      there is a lack of evidence for a direct relationship between a well
      characterized decline in NMDAR function and impaired cognition during aging. The
      present study was designed to test the idea that a redox-mediated decrease in the
      NMDAR component of synaptic transmission during aging is related to a specific
      cognitive phenotype: impaired memory for rapidly acquired novel spatial
      information. Young and middle-aged male F344 rats were provided 1 d of training
      on the spatial version of the water maze, and retention was examined 24 h later.
      The performance of young rats was used as a criterion for classifying middle-aged
      rats as impaired and unimpaired on the task. Subsequent construction of CA3-CA1
      synaptic input-output curves in hippocampal slices confirmed an age-related
      decrease in synaptic responses, including the NMDAR component of synaptic
      transmission. Examination of synaptic transmission according to behavioral
      classification revealed that animals classified as impaired exhibited a decrease
      in the total and the NMDAR component of the synaptic response relative to
      unimpaired animals. Furthermore, bath application of the reducing agent
      dithiothreitol increased the NMDAR component of the synaptic response to a
      greater extent in impaired animals relative to unimpaired and young rats. These
      results provide evidence for a link between the redox-mediated decline in NMDAR
      function and emergence of an age-related cognitive phenotype, impairment in the
      rapid acquisition and retention of novel spatial information. 

PMID- 24089480
TI  - Role of medial prefrontal cortex serotonin 2A receptors in the control of
      retrieval of recognition memory in rats.
AB  - Often, retrieval cues are not uniquely related to one specific memory, which
      could lead to memory interference. Controlling interference is particularly
      important during episodic memory retrieval or when remembering specific events in
      a spatiotemporal context. Despite a clear involvement of prefrontal cortex (PFC)
      in episodic memory in human studies, information regarding the mechanisms and
      neurotransmitter systems in PFC involved in memory is scarce. Although the
      serotoninergic system has been linked to PFC functionality and modulation, its
      role in memory processing is poorly understood. We hypothesized that the
      serotoninergic system in PFC, in particular the 5-HT2A receptor (5-HT2AR) could
      have a role in the control of memory retrieval. In this work we used different
      versions of the object recognition task in rats to study the role of the
      serotoninergic modulation in the medial PFC (mPFC) in memory retrieval. We found
      that blockade of 5-HT2AR in mPFC affects retrieval of an object in context memory
      in a spontaneous novelty preference task, while sparing single-item recognition
      memory. We also determined that 5-HT2ARs in mPFC are required for hippocampal
      mPFC interaction during retrieval of this type of memory, suggesting that the
      mPFC controls the expression of memory traces stored in the hippocampus biasing
      retrieval to the most relevant one. 

PMID- 24089481
TI  - Zebrafish embryonic neurons transport messenger RNA to axons and growth cones in
      vivo.
AB  - Although mRNA was once thought to be excluded from the axonal compartment, the
      existence of protein synthesis in growing or regenerating axons in culture is now
      generally accepted. However, its extent and functional importance remain a
      subject of intense investigation. Furthermore, unambiguous evidence of mRNA
      axonal transport and local translation in vivo, in the context of a whole
      developing organism is still lacking. Here, we provide direct evidence of the
      presence of mRNAs of the tubb5, nefma, and stmnb2 genes in several types of axons
      in the developing zebrafish (Danio rerio) embryo, with frequent accumulation at
      the growth cone. We further show that axonal localization of mRNA is a specific
      property of a subset of genes, as mRNAs of the huc and neurod genes, abundantly
      expressed in neurons, were not found in axons. We set up a reporter system in
      which the 3' untranslated region (UTR) of candidate mRNA, fused to a fluorescent
      protein coding sequence, was expressed in isolated neurons of the zebrafish
      embryo. Using this reporter, we identified in the 3'UTR of tubb5 mRNA a motif
      necessary and sufficient for axonal localization. Our work thus establishes the
      zebrafish as a model system to study axonal transport in a whole developing
      vertebrate organism, provides an experimental frame to assay this transport in
      vivo and to study its mechanisms, and identifies a new zipcode involved in axonal
      mRNA localization. 

PMID- 24089482
TI  - Filamin A regulates neuronal migration through brefeldin A-inhibited guanine
      exchange factor 2-dependent Arf1 activation.
AB  - Periventricular heterotopias is a malformation of cortical development,
      characterized by ectopic neuronal nodules around ventricle lining and caused by
      an initial migration defect during early brain development. Human mutations in
      the Filamin A (FLNA) and ADP-ribosylation factor guanine exchange factor 2
      [ARFGEF2; encoding brefeldin-A-inhibited guanine exchange factor-2 (BIG2)] genes
      give rise to this disorder. Previously, we have reported that Big2 inhibition
      impairs neuronal migration and binds to FlnA, and its loss promotes FlnA
      phosphorylation. FlnA phosphorylation dictates FlnA-actin binding affinity and
      consequently alters focal adhesion size and number to effect neuronal migration.
      Here we show that FlnA loss similarly impairs migration, reciprocally enhances
      Big2 expression, but also alters Big2 subcellular localization in both null and
      conditional FlnA mice. FlnA phosphorylation promotes relocalization of Big2 from
      the Golgi toward the lipid ruffles, thereby activating Big2-dependent Arf1 at the
      cell membrane. Loss of FlnA phosphorylation or Big2 function impairs Arf1
      dependent vesicle trafficking at the periphery, and Arf1 is required for
      maintenance of cell-cell junction connectivity and focal adhesion assembly. Loss
      of Arf1 activity disrupts neuronal migration and cell adhesion. Collectively,
      these studies demonstrate a potential mechanism whereby coordinated interactions
      between actin (through FlnA) and vesicle trafficking (through Big2-Arf) direct
      the assembly and disassembly of membrane protein complexes required for neuronal
      migration and neuroependymal integrity. 

PMID- 24089483
TI  - Mechanisms for stable, robust, and adaptive development of orientation maps in
      the primary visual cortex.
AB  - Development of orientation maps in ferret and cat primary visual cortex (V1) has
      been shown to be stable, in that the earliest measurable maps are similar in form
      to the eventual adult map, robust, in that similar maps develop in both dark
      rearing and in a variety of normal visual environments, and yet adaptive, in that
      the final map pattern reflects the statistics of the specific visual environment.
      How can these three properties be reconciled? Using mechanistic models of the
      development of neural connectivity in V1, we show for the first time that
      realistic stable, robust, and adaptive map development can be achieved by
      including two low-level mechanisms originally motivated from single-neuron
      results. Specifically, contrast-gain control in the retinal ganglion cells and
      the lateral geniculate nucleus reduces variation in the presynaptic drive due to
      differences in input patterns, while homeostatic plasticity of V1 neuron
      excitability reduces the postsynaptic variability in firing rates. Together these
      two mechanisms, thought to be applicable across sensory systems in general, lead
      to biological maps that develop stably and robustly, yet adapt to the visual
      environment. The modeling results suggest that topographic map stability is a
      natural outcome of low-level processes of adaptation and normalization. The
      resulting model is more realistic, simpler, and far more robust, and is thus a
      good starting point for future studies of cortical map development. 

PMID- 24089485
TI  - Superficially projecting principal neurons in layer V of medial entorhinal cortex
      in the rat receive excitatory retrosplenial input.
AB  - Principal cells in layer V of the medial entorhinal cortex (MEC) have a nodal
      position in the cortical-hippocampal network. They are the main recipients of
      hippocampal output and receive inputs from several cortical areas, including a
      prominent one from the retrosplenial cortex (RSC), likely targeting basal
      dendrites of layer V neurons. The latter project to extrahippocampal structures
      but also relay information to the superficial layers of MEC, closing the
      hippocampal-entorhinal loop. In the rat, we electrophysiologically and
      morphologically characterized RSC input into MEC and conclude that RSC provides
      an excitatory input to layer V pyramidal cells. Ultrastructural analyses of
      anterogradely labeled RSC projections showed that RSC axons in layer V of MEC
      form predominantly asymmetrical, likely excitatory, synapses on dendritic spines
      (90%) or shafts (8%), with 2% symmetrical, likely inhibitory, synapses on shafts
      and spines. The overall excitatory nature of the RSC input was confirmed by an
      optogenetic approach. Patterned laser stimulation of channelrhodopsin-expressing
      presynaptic RSC axons evoked exclusively EPSPs in recorded postsynaptic layer V
      cells. All responding layer V pyramidal cells had an axon extending toward the
      white matter. Half of these neurons also sent an axon to superficial layers.
      Confocal imaging of RSC synapses onto MEC layer V neurons shown to project
      superficially by way of retrogradely labeling from superficial layers confirmed
      that proximal dendrites of superficially projecting cells are among the targets
      of inputs from RSC. The excitatory RSC input thus interacts with both entorhinal
      cortical and entorhinal-hippocampal circuits. 

PMID- 24089486
TI  - Actin polymerization does not provide direct mechanical forces for vesicle
      fission during clathrin-mediated endocytosis.
AB  - Actin polymerization is important for vesicle fission during clathrin-mediated
      endocytosis (CME), and it has been proposed that actin polymerization may promote
      vesicle fission during CME by providing direct mechanical forces. However, there
      is no direct evidence in support of this hypothesis. In the present study, the
      role of actin polymerization in vesicle fission was tested by analyzing the
      kinetics of the endocytic tubular membrane neck (the fission-pore) with cell
      attached capacitance measurements to detect CME of single vesicles in a
      millisecond time resolution in mouse chromaffin cells. Inhibition in dynamin
      GTPase activity increased the fission-pore conductance (Gp), supporting the
      mechanical role of dynamin GTPase in vesicle fission. However, disruptions in
      actin polymerization did not alter the fission-pore conductance Gp, thus arguing
      against the force-generating role of actin polymerization in vesicle fission
      during CME. Similar to disruptions of actin polymerization, cholesterol depletion
      results in an increase in the fission-pore duration, indicating a role for
      cholesterol-dependent membrane reorganization in vesicle fission. Further
      experiments suggested that actin polymerization and cholesterol might function in
      vesicle fission during CME in the same pathway. Our results thus support a model
      in which actin polymerization promotes vesicle fission during CME by inducing
      cholesterol-dependent membrane reorganization. 

PMID- 24089487
TI  - Oscillatory phase dynamics in neural entrainment underpin illusory percepts of
      time.
AB  - Neural oscillatory dynamics are a candidate mechanism to steer perception of time
      and temporal rate change. While oscillator models of time perception are strongly
      supported by behavioral evidence, a direct link to neural oscillations and
      oscillatory entrainment has not yet been provided. In addition, it has thus far
      remained unaddressed how context-induced illusory percepts of time are coded for
      in oscillator models of time perception. To investigate these questions, we used
      magnetoencephalography and examined the neural oscillatory dynamics that underpin
      pitch-induced illusory percepts of temporal rate change. Human participants
      listened to frequency-modulated sounds that varied over time in both modulation
      rate and pitch, and judged the direction of rate change (decrease vs increase).
      Our results demonstrate distinct neural mechanisms of rate perception: Modulation
      rate changes directly affected listeners' rate percept as well as the exact
      frequency of the neural oscillation. However, pitch-induced illusory rate changes
      were unrelated to the exact frequency of the neural responses. The rate change
      illusion was instead linked to changes in neural phase patterns, which allowed
      for single-trial decoding of percepts. That is, illusory underestimations or
      overestimations of perceived rate change were tightly coupled to increased
      intertrial phase coherence and changes in cerebro-acoustic phase lag. The results
      provide insight on how illusory percepts of time are coded for by neural
      oscillatory dynamics. 

PMID- 24089484
TI  - Shank3 deficiency induces NMDA receptor hypofunction via an actin-dependent
      mechanism.
AB  - Shank3, which encodes a scaffolding protein at glutamatergic synapses, is a
      genetic risk factor for autism. In this study, we examined the impact of Shank3
      deficiency on the NMDA-type glutamate receptor, a key player in cognition and
      mental illnesses. We found that knockdown of Shank3 with a small interfering RNA
      (siRNA) caused a significant reduction of NMDAR-mediated ionic or synaptic
      current, as well as the surface expression of NR1 subunits, in rat cortical
      cultures. The effect of Shank3 siRNA on NMDAR currents was blocked by an actin
      stabilizer, and was occluded by an actin destabilizer, suggesting the involvement
      of actin cytoskeleton. Since actin dynamics is regulated by the GTPase Rac1 and
      downstream effector p21-activated kinase (PAK), we further examined Shank3
      regulation of NMDARs when Rac1 or PAK was manipulated. We found that the reducing
      effect of Shank3 siRNA on NMDAR currents was mimicked and occluded by specific
      inhibitors for Rac1 or PAK, and was blocked by constitutively active Rac1 or PAK.
      Immunocytochemical data showed a strong reduction of F-actin clusters after
      Shank3 knockdown, which was occluded by a PAK inhibitor. Inhibiting cofilin, the
      primary downstream target of PAK and a major actin depolymerizing factor,
      prevented Shank3 siRNA from reducing NMDAR currents and F-actin clusters.
      Together, these results suggest that Shank3 deficiency induces NMDAR hypofunction
      by interfering with the Rac1/PAK/cofilin/actin signaling, leading to the loss of
      NMDAR membrane delivery or stability. It provides a potential mechanism for the
      role of Shank3 in cognitive deficit in autism. 

PMID- 24089488
TI  - Risk prediction error coding in orbitofrontal neurons.
AB  - Risk is a ubiquitous feature of life. It plays an important role in economic
      decisions by affecting subjective reward value. Informed decisions require
      accurate risk information for each choice option. However, risk is often not
      constant but changes dynamically in the environment. Therefore, risk information
      should be updated to the current risk level. Potential mechanisms involve error
      driven updating, whereby differences between current and predicted risk levels
      (risk prediction errors) are used to obtain currently accurate risk predictions.
      As a major reward structure, the orbitofrontal cortex is involved in coding key
      reward parameters such as reward value and risk. In this study, monkeys viewed
      different visual stimuli indicating specific levels of risk that deviated from
      the overall risk predicted by a common earlier stimulus. A group of orbitofrontal
      neurons displayed a risk signal that tracked the discrepancy between current and
      predicted risk. Such neuronal signals may be involved in the updating of risk
      information. 

PMID- 24089489
TI  - Cognitive factors modulate activity within the human subthalamic nucleus during
      voluntary movement in Parkinson's disease.
AB  - Movement is accompanied by changes in the degree to which neurons in corticobasal
      ganglia loops synchronize their activity within discrete frequency ranges.
      Although two principal frequency bands--beta (15-30 Hz) and gamma (60-90 Hz)-
      have been implicated in motor control, the precise functional correlates of their
      activities remain unclear. Local field potential (LFP) recordings in humans with
      Parkinson's disease undergoing surgery for deep brain stimulation to the
      subthalamic nucleus (STN) indicate that spectral changes both anticipate movement
      and occur perimovement. The extent to which such changes are modulated by
      cognitive factors involved in making a correct response seems critical in
      characterizing the functional associations of these oscillations. Accordingly, by
      recording LFP activity from the STN in parkinsonian patients, we demonstrate that
      perimovement beta and gamma reactivity is modulated by task complexity in a
      dopamine-dependent manner, despite the dynamics of the movement remaining
      unchanged. In contrast, spectral changes occurring in anticipation of future
      movement were limited to the beta band and, although modulated by dopaminergic
      therapy, were not modulated by task complexity. Our findings suggest two dopamine
      dependent processes indexed by spectral changes in the STN: (1) an anticipatory
      activity reflected in the beta band that signals the likelihood of future action
      but does not proactively change with the cognitive demands of the potential
      response, and (2) perimovement activity that involves reciprocal beta and gamma
      band changes and is not exclusively related to explicit motor processing. Rather
      perimovement activity can also vary with, and may reflect, the cognitive
      complexity of the task.

PMID- 24089490
TI  - Chronic cocaine dampens dopamine signaling during cocaine intoxication and
      unbalances D1 over D2 receptor signaling.
AB  - Dopamine increases triggered by cocaine and consequent stimulation of dopamine
      receptors (including D1 and D2) are associated with its rewarding effects.
      However, while facilitation of D1 receptor (D1R) signaling enhances the rewarding
      effects of cocaine, facilitation of D2R signaling decreases it, which indicates
      that for cocaine to be rewarding it must result in a predominance of D1R over D2R
      signaling. Moreover, the transition to compulsive cocaine intake might result
      from an imbalance between D1R and D2R signaling. To test the hypothesis that
      chronic cocaine use unbalances D1R over D2R signaling during cocaine
      intoxication, we used microprobe optical imaging to compare dynamic changes in
      intracellular calcium ([Ca(2+)]i, marker of neuronal activation) to acute cocaine
      in striatal D1R-EGFP and D2R-EGFP-expressing neurons between control and
      chronically treated mice. Chronic cocaine attenuated responses to acute cocaine
      in D1R (blunting Ca(2+) increases by 67 +/- 16%) and D2R (blunting Ca(2+)
      decrease by 72 +/- 17%) neurons in most D1R and D2R neurons (~75%). However, the
      dynamics of this attenuation during cocaine intoxication was longer lasting for
      D2R than for D1R. Thus, whereas control mice showed a fast but short-lasting
      predominance of D1R over D2R signaling (peaking at ~8 min) during acute cocaine
      intoxication, in chronically treated mice D1R predominance was sustained for >30
      min (throughout the measurement period). Thus, chronic cocaine use dramatically
      reduced cocaine-induced DA signaling, shifting the balance between D1R and D2R
      signaling during intoxication to a predominance of D1R (stimulatory) over D2R
      (inhibitory) signaling, which might facilitate compulsive intake in addiction.

PMID- 24089491
TI  - Decoding sound source location and separation using neural population activity
      patterns.
AB  - The strategies by which the central nervous system decodes the properties of
      sensory stimuli, such as sound source location, from the responses of a
      population of neurons are a matter of debate. We show, using the average firing
      rates of neurons in the inferior colliculus (IC) of awake rabbits, that
      prevailing decoding models of sound localization (summed population activity and
      the population vector) fail to localize sources accurately due to heterogeneity
      in azimuth tuning across the population. In contrast, a maximum-likelihood
      decoder operating on the pattern of activity across the population of neurons in
      one IC accurately localized sound sources in the contralateral hemifield,
      consistent with lesion studies, and did so with a precision consistent with
      rabbit psychophysical performance. The pattern decoder also predicts behavior in
      response to incongruent localization cues consistent with the long-standing
      "duplex" theory of sound localization. We further show that the pattern decoder
      accurately distinguishes two concurrent, spatially separated sources from a
      single source, consistent with human behavior. Decoder detection of small amounts
      of source separation directly in front is due to neural sensitivity to the
      interaural decorrelation of sound, at both low and high frequencies. The distinct
      patterns of IC activity between single and separated sound sources thereby
      provide a neural correlate for the ability to segregate and localize sources in
      everyday, multisource environments. 

PMID- 24089492
TI  - Stochastic calcium mechanisms cause dendritic calcium spike variability.
AB  - Bursts of dendritic calcium spikes play an important role in excitability and
      synaptic plasticity in many types of neurons. In single Purkinje cells,
      spontaneous and synaptically evoked dendritic calcium bursts come in a variety of
      shapes with a variable number of spikes. The mechanisms causing this variability
      have never been investigated thoroughly. In this study, a detailed computational
      model using novel simulation routines is applied to identify the roles that
      stochastic ion channels, spatial arrangements of ion channels, and stochastic
      intracellular calcium have toward producing calcium burst variability. Consistent
      with experimental recordings from rats, strong variability in the burst shape is
      observed in simulations. This variability persists in large model sizes in
      contrast to models containing only voltage-gated channels, where variability
      reduces quickly with increase of system size. Phase plane analysis of Hodgkin
      Huxley spikes and of calcium bursts identifies fluctuation in phase space around
      probabilistic phase boundaries as the mechanism determining the dependence of
      variability on model size. Stochastic calcium dynamics are the main cause of
      calcium burst fluctuations, specifically the calcium activation of mslo/BK-type
      and SK2 channels. Local variability of calcium concentration has a significant
      effect at larger model sizes. Simulations of both spontaneous and synaptically
      evoked calcium bursts in a reconstructed dendrite show, in addition, strong
      spatial and temporal variability of voltage and calcium, depending on
      morphological properties of the dendrite. Our findings suggest that stochastic
      intracellular calcium mechanisms play a crucial role in dendritic calcium spike
      generation and are therefore an essential consideration in studies of neuronal
      excitability and plasticity. 

PMID- 24089493
TI  - Facilitation of inferior frontal cortex by transcranial direct current
      stimulation induces perceptual learning of severely degraded speech.
AB  - Perceptual learning requires the generalization of categorical perceptual
      sensitivity from trained to untrained items. For degraded speech, perceptual
      learning modulates activation in a left-lateralized network, including inferior
      frontal gyrus (IFG) and inferior parietal cortex (IPC). Here we demonstrate that
      facilitatory anodal transcranial direct current stimulation (tDCS(anodal)) can
      induce perceptual learning in healthy humans. In a sham-controlled, parallel
      design study, 36 volunteers were allocated to the three following intervention
      groups: tDCS(anodal) over left IFG, IPC, or sham. Participants decided on the
      match between an acoustically degraded and an undegraded written word by forced
      same-different choice. Acoustic degradation varied in four noise-vocoding levels
      (2, 3, 4, and 6 bands). Participants were trained to discriminate between minimal
      (/Tisch/-FISCH) and identical word pairs (/Tisch/-TISCH) over a period of 3 d,
      and tDCS(anodal) was applied during the first 20 min of training. Perceptual
      sensitivity (d') for trained word pairs, and an equal number of untrained word
      pairs, was tested before and after training. Increases in d' indicate perceptual
      learning for untrained word pairs, and a combination of item-specific and
      perceptual learning for trained word pairs. Most notably for the lowest
      intelligibility level, perceptual learning occurred only when tDCS(anodal) was
      applied over left IFG. For trained pairs, improved d' was seen on all
      intelligibility levels regardless of tDCS intervention. Over left IPC,
      tDCS(anodal) did not modulate learning but instead introduced a response bias
      during training. Volunteers were more likely to respond "same," potentially
      indicating enhanced perceptual fusion of degraded auditory with undegraded
      written input. Our results supply first evidence that neural facilitation of
      higher-order language areas can induce perceptual learning of severely degraded
      speech.

PMID- 24089494
TI  - TNF-alpha downregulates inhibitory neurotransmission through protein phosphatase
      1-dependent trafficking of GABA(A) receptors.
AB  - Inflammation has been implicated in the progression of neurological disease, yet
      precisely how inflammation affects neuronal function remains unclear. Tumor
      necrosis factor-alpha (TNFalpha) is a proinflammatory cytokine that regulates
      synapse function by controlling neurotransmitter receptor trafficking and
      homeostatic synaptic plasticity. Here we characterize the mechanisms through
      which TNFalpha regulates inhibitory synapse function in mature rat and mouse
      hippocampal neurons. Acute application of TNFalpha induces a rapid and persistent
      decrease of inhibitory synaptic strength and downregulation of cell-surface
      levels of GABA(A)Rs containing alpha1, alpha2, beta2/3, and gamma2 subunits. We
      show that trafficking of GABA(A)Rs in response to TNFalpha is mediated by
      neuronally expressed TNF receptor 1 and requires activation of p38 MAPK,
      phosphatidylinositol 3-kinase, protein phosphatase 1 (PP1), and dynamin GTPase.
      Furthermore, TNFalpha enhances the association of PP1 with GABA(A)R beta3
      subunits and dephosphorylates a site on beta3 known to regulate phospho-dependent
      interactions with the endocytic machinery. Conversely, we find that calcineurin
      and PP2A are not essential components of the signaling pathway and that
      clustering of the scaffolding protein gephyrin is only reduced after the initial
      receptor endocytosis. Together, these findings demonstrate a distinct mechanism
      of regulated GABA(A)R endocytosis that may contribute to the disruption of
      circuit homeostasis under neuroinflammatory conditions.

PMID- 24089495
TI  - Imaging social motivation: distinct brain mechanisms drive effort production
      during collaboration versus competition.
AB  - Collaborative and competitive interactions have been investigated extensively so
      as to understand how the brain makes choices in the context of strategic games,
      yet such interactions are known to influence a more basic dimension of behavior:
      the energy invested in the task. The cognitive mechanisms that motivate effort
      production in social situations remain poorly understood, and their neural
      counterparts have not been explored so far. A dominant idea is that the
      motivation provided by the social context is reducible to the personal utility of
      effort production, which decreases in collaboration and increases in competition.
      Using functional magnetic resonance imaging, we scanned human participants while
      they produced a physical effort in a collaborative or competitive context. We
      found that motivation was indeed primarily driven by personal utility, which was
      reflected in brain regions devoted to reward processing (the ventral basal
      ganglia). However, subjects who departed from utility maximization, working more
      in collaborative situations, showed greater functional activation and anatomical
      volume in a brain region implicated previously in social cognition (the
      temporoparietal junction). Therefore, this region might mediate a purely pro
      social motivation to produce greater effort in the context of collaboration. More
      generally, our findings suggest that the individual propensity to invest energy
      in collaborative work might have an identifiable counterpart in the brain
      functional architecture. 

PMID- 24089496
TI  - Rapid feedback responses correlate with reach adaptation and properties of novel
      upper limb loads.
AB  - A hallmark of voluntary motor control is the ability to adjust motor patterns for
      novel mechanical or visuomotor contexts. Recent work has also highlighted the
      importance of feedback for voluntary control, leading to the hypothesis that
      feedback responses should adapt when we learn new motor skills. We tested this
      prediction with a novel paradigm requiring that human subjects adapt to a viscous
      elbow load while reaching to three targets. Target 1 required combined shoulder
      and elbow motion, target 2 required only elbow motion, and target 3 (probe
      target) required shoulder but no elbow motion. This simple approach controlled
      muscle activity at the probe target before, during, and after the application of
      novel elbow loads. Our paradigm allowed us to perturb the elbow during reaching
      movements to the probe target and identify several key properties of adapted
      stretch responses. Adapted long-latency responses expressed (de-) adaptation
      similar to reaching errors observed when we introduced (removed) the elbow load.
      Moreover, reaching errors during learning correlated with changes in the long
      latency response, showing subjects who adapted more to the elbow load displayed
      greater modulation of their stretch responses. These adapted responses were
      sensitive to the size and direction of the viscous training load. Our results
      highlight an important link between the adaptation of feedforward and feedback
      control and suggest a key part of motor adaptation is to adjust feedback
      responses to the requirements of novel motor skills. 

PMID- 24089497
TI  - Heterosynaptic plasticity prevents runaway synaptic dynamics.
AB  - Spike timing-dependent plasticity (STDP) and other conventional Hebbian-type
      plasticity rules are prone to produce runaway dynamics of synaptic weights. Once
      potentiated, a synapse would have higher probability to lead to spikes and thus
      to be further potentiated, but once depressed, a synapse would tend to be further
      depressed. The runaway synaptic dynamics can be prevented by precisely balancing
      STDP rules for potentiation and depression; however, experimental evidence shows
      a great variety of potentiation and depression windows and magnitudes. Here we
      show that modifications of synapses to layer 2/3 pyramidal neurons from rat
      visual and auditory cortices in slices can be induced by intracellular
      tetanization: bursts of postsynaptic spikes without presynaptic stimulation.
      Induction of these heterosynaptic changes depended on the rise of intracellular
      calcium, and their direction and magnitude correlated with initial state of
      release mechanisms. We suggest that this type of plasticity serves as a mechanism
      that stabilizes the distribution of synaptic weights and prevents their runaway
      dynamics. To test this hypothesis, we develop a cortical neuron model
      implementing both homosynaptic (STDP) and heterosynaptic plasticity with
      properties matching the experimental data. We find that heterosynaptic plasticity
      effectively prevented runaway dynamics for the tested range of STDP and input
      parameters. Synaptic weights, although shifted from the original, remained
      normally distributed and nonsaturated. Our study presents a biophysically
      constrained model of how the interaction of different forms of plasticity-
      Hebbian and heterosynaptic--may prevent runaway synaptic dynamics and keep
      synaptic weights unsaturated and thus capable of further plastic changes and
      formation of new memories.

PMID- 24089498
TI  - Where pain meets action in the human brain.
AB  - Pain's complex influence on behavior implies that it involves an action
      component, although little is known about how the human brain adaptively
      translates painful sensations into actions. The consistent activation of premotor
      and motor-related regions during pain, including the midcingulate cortex (MCC),
      raises the question of whether these areas contribute to an action component. In
      this fMRI experiment, we controlled for voluntary action-related processing
      during pain by introducing a motor task during painful or nonpainful stimulation.
      The MCC (particularly the caudal cingulate motor zone [CCZ]), motor cortex,
      thalamus, and cerebellum responded during action regardless of pain. Crucially,
      however, these regions did not respond to pain unless an action was performed.
      Reaction times were fastest during painful stimulation and correlated with CCZ
      activation. These findings are consistent with the results of an activation
      likelihood estimate meta-analysis in which activation across experiments
      involving pain, action execution, or action preparation (with a total of 4929
      subjects) converged in a similar network. These findings suggest that specific
      motor-related areas, including the CCZ, play a vital role in the control and
      execution of context-sensitive behavioral responses to pain. In contrast,
      bilateral insular cortex responded to pain stimulation regardless of action. 

PMID- 24089499
TI  - Pea3 transcription factor family members Etv4 and Etv5 mediate retrograde
      signaling and axonal growth of DRG sensory neurons in response to NGF.
AB  - Nerve growth factor (NGF) is a target-derived neurotrophic growth factor that
      controls many aspects of sensory and sympathetic neuronal development. The
      identification of transcription factors and downstream target genes that mediate
      NGF-dependent neuronal differentiation and target field innervation is currently
      a major challenge. Here, we show that the Pea3 transcription factor family
      members Etv4 and Etv5 are expressed by developing TrkA-positive dorsal root
      ganglion (DRG) neurons during the period of target innervation. Real-time PCR
      assays indicated that Etv4 and Etv5 mRNAs are significantly induced by NGF in
      different neuronal cells, suggesting that they could be involved in the
      biological responses induced by this neurotrophin. Interestingly, distal axon
      application of NGF in compartmentalized cultures of rat DRG sensory neurons was
      sufficient to induce a significant increase in Etv4 and Etv5 mRNA expression.
      Pharmacological assays also revealed that activation of MEK/ERK (MAPK) pathway is
      required for Etv4 and Etv5 gene induction in response to NGF. Downregulation of
      Etv4 and Etv5 using small interference RNA knockdown experiments inhibited NGF
      induced neurite outgrowth of rat sensory neurons, while overexpression of full
      length Etv4 or Etv5 potentiated neuronal differentiation in response to this
      neurotrophin. Together, these data establish Etv4 and Etv5 as essential molecules
      of the transcriptional program linking neurotrophin signaling to sensory neuronal
      differentiation, and suggest that they can be involved in NGF-mediated target
      innervation. 

PMID- 24089500
TI  - Blockade of Toll-like receptor 4 attenuates morphine tolerance and facilitates
      the pain relieving properties of morphine.
AB  - The ventrolateral periaqueductal gray (vlPAG) is an integral locus for morphine
      action. Although it is clear that glia contribute to the development of morphine
      tolerance, to date, the investigation of their role has been limited to spinal
      and medullary loci. Opioids induce a neuroinflammatory response that opposes
      acute and long-term analgesia, thereby limiting their efficacy as therapeutic
      agents. Recent data suggest that the innate immune receptor Toll-like receptor 4
      (TLR4), along with its coreceptor myeloid differentiation factor-2 (MD-2),
      mediates these effects. To date, the brain loci through which TLR4 modulates
      morphine tolerance have not been identified. We have previously demonstrated that
      chronic subcutaneous morphine results in tolerance that is accompanied by
      increases in vlPAG glial cell activity. Using in vivo pharmacological
      manipulations of vlPAG glia and TLR4 in the adult male rat, we show that intra
      vlPAG administration of the general glial cell metabolic inhibitor
      propentofylline or the astrocyte activity inhibitor fluorocitrate attenuate
      tolerance to morphine. Characterization of MD-2 expression within the PAG
      revealed dense MD-2 expression throughout the vlPAG. Further, antagonizing vlPAG
      TLR4 dose dependently prevented the development of morphine tolerance, and vlPAG
      microinjections of TLR4 agonists dose dependently produced a "naive" tolerance to
      subsequent challenge doses of morphine. Finally, using a model of persistent
      inflammatory pain and pharmacological manipulation of TLR4 we demonstrate that
      systemic antagonism of TLR4 potentiated acute morphine antihyperalgesia. These
      results, together, indicate that vlPAG glia regulate morphine tolerance
      development via TLR4 signaling, and implicate TLR4 as a potential therapeutic
      target for the treatment of pain. 

PMID- 24089501
TI  - Activation of synaptic group II metabotropic glutamate receptors induces long
      term depression at GABAergic synapses in CNS neurons.
AB  - Metabotropic glutamate receptor (mGluR)-dependent homosynaptic long-term
      depression (LTD) has been studied extensively at glutamatergic synapses in the
      CNS. However, much less is known about heterosynaptic long-term plasticity
      induced by mGluRs at inhibitory synapses. Here we report that pharmacological or
      synaptic activation of group II mGluRs (mGluR II) induces LTD at GABAergic
      synapses without affecting the excitatory glutamatergic transmission in neurons
      of the chicken cochlear nucleus. Coefficient of variation and failure rate
      analysis suggested that the LTD was expressed presynaptically. The LTD requires
      presynaptic spike activity, but does not require the activation of NMDA
      receptors. The classic cAMP-dependent protein kinase A signaling is involved in
      the transduction pathway. Remarkably, blocking mGluR II increased spontaneous
      GABA release, indicating the presence of tonic activation of mGluR II by ambient
      glutamate. Furthermore, synaptically released glutamate induced by electrical
      stimulations that concurrently activated both the glutamatergic and GABAergic
      pathways resulted in significant and constant suppression of GABA release at
      various stimulus frequencies (3.3, 100, and 300 Hz). Strikingly, low-frequency
      stimulation (1 Hz, 15 min) of the glutamatergic synapses induced heterosynaptic
      LTD of GABAergic transmission, and the LTD was blocked by mGluR II antagonist,
      indicating that synaptic activation of mGluR II induced the LTD. This novel form
      of long-term plasticity in the avian auditory brainstem may play a role in the
      development as well as in temporal processing in the sound localization circuit. 

PMID- 24089502
TI  - Selective and invariant neural responses to spoken and written narratives.
AB  - Linguistic content can be conveyed both in speech and in writing. But how similar
      is the neural processing when the same real-life information is presented in
      spoken and written form? Using functional magnetic resonance imaging, we recorded
      neural responses from human subjects who either listened to a 7 min spoken
      narrative or read a time-locked presentation of its transcript. Next, within each
      brain area, we directly compared the response time courses elicited by the
      written and spoken narrative. Early visual areas responded selectively to the
      written version, and early auditory areas to the spoken version of the narrative.
      In addition, many higher-order parietal and frontal areas demonstrated strong
      selectivity, responding far more reliably to either the spoken or written form of
      the narrative. By contrast, the response time courses along the superior temporal
      gyrus and inferior frontal gyrus were remarkably similar for spoken and written
      narratives, indicating strong modality-invariance of linguistic processing in
      these circuits. These results suggest that our ability to extract the same
      information from spoken and written forms arises from a mixture of selective
      neural processes in early (perceptual) and high-order (control) areas, and
      modality-invariant responses in linguistic and extra-linguistic areas. 

PMID- 24089503
TI  - The orbitofrontal cortex as part of a hierarchical neural system mediating choice
      between two good options.
AB  - Animals rely on environmental cues to identify potential rewards and select the
      best reward available. The orbitofrontal cortex (OFC) is proposed to encode
      sensory-specific representations of expected outcome. However, its contribution
      to the selection of a preferred outcome among different reward options is still
      unclear. We investigated the effect of transient OFC inactivation (achieved by
      presession injection of muscimol and baclofen) in a novel two-reward choice task.
      In discrete trials, rats could choose between a solution of polycose and an
      equally caloric, but highly preferred, solution of sucrose by visiting one of two
      liquid dispensers after the presentation of a specific cue signaling the
      availability of one or both of the solutions. We found that OFC inactivation did
      not affect outcome preference: rats maintained high preference for sucrose and
      adapted their behavioral responding when the cue-outcome contingencies were
      reversed. However, when rats were tested drug-free 24 h after OFC inactivation
      and reversal learning, memory for the newly learned contingencies was poor. These
      results suggest a potential conflict between OFC (encoding pre-reversal
      contingencies) and other brain circuits (encoding the new contingencies).
      Remarkably, repeating the OFC inactivation before the reversal memory test
      restored normal behavior, confirming the hypothesis of a dominant impact of OFC
      on other decision-making circuits. These results indicate that the
      representations encoded in the OFC, while not essential to the expression of
      outcome preference, exert hierarchical control on downstream decision-making
      circuits. 

PMID- 24089505
TI  - Frontoparietal cortex mediates perceptual transitions in bistable perception.
AB  - During bistable vision, perception oscillates between two mutually exclusive
      percepts despite constant sensory input. Greater BOLD responses in frontoparietal
      cortex have been shown to be associated with endogenous perceptual transitions
      compared with "replay" transitions designed to closely match bistability in both
      perceptual quality and timing. It has remained controversial, however, whether
      this enhanced activity reflects causal influences of these regions on processing
      at the sensory level or, alternatively, an effect of stimulus differences that
      result in, for example, longer durations of perceptual transitions in bistable
      perception compared with replay conditions. Using a rotating Lissajous figure in
      an fMRI experiment on 15 human participants, we controlled for potential
      confounds of differences in transition duration and confirmed previous findings
      of greater activity in frontoparietal areas for transitions during bistable
      perception. In addition, we applied dynamic causal modeling to identify the
      neural model that best explains the observed BOLD signals in terms of effective
      connectivity. We found that enhanced activity for perceptual transitions is
      associated with a modulation of top-down connectivity from frontal to visual
      cortex, thus arguing for a crucial role of frontoparietal cortex in perceptual
      transitions during bistable perception. 

PMID- 24089504
TI  - Blood oxygen level-dependent activation of the primary visual cortex predicts
      size adaptation illusion.
AB  - In natural scenes, objects rarely occur in isolation but appear within a
      spatiotemporal context. Here, we show that the perceived size of a stimulus is
      significantly affected by the context of the scene: brief previous presentation
      of larger or smaller adapting stimuli at the same region of space changes the
      perceived size of a test stimulus, with larger adapting stimuli causing the test
      to appear smaller than veridical and vice versa. In a human fMRI study, we
      measured the blood oxygen level-dependent activation (BOLD) responses of the
      primary visual cortex (V1) to the contours of large-diameter stimuli and found
      that activation closely matched the perceptual rather than the retinal stimulus
      size: the activated area of V1 increased or decreased, depending on the size of
      the preceding stimulus. A model based on local inhibitory V1 mechanisms simulated
      the inward or outward shifts of the stimulus contours and hence the perceptual
      effects. Our findings suggest that area V1 is actively involved in reshaping our
      perception to match the short-term statistics of the visual scene. 

PMID- 24089506
TI  - Suppression of inflammation with conditional deletion of the prostaglandin E2 EP2
      receptor in macrophages and brain microglia.
AB  - Prostaglandin E2 (PGE2), a potent lipid signaling molecule, modulates
      inflammatory responses through activation of downstream G-protein coupled EP(1-4)
      receptors. Here, we investigated the cell-specific in vivo function of PGE2
      signaling through its E-prostanoid 2 (EP2) receptor in murine innate immune
      responses systemically and in the CNS. In vivo, systemic administration of
      lipopolysaccharide (LPS) resulted in a broad induction of cytokines and
      chemokines in plasma that was significantly attenuated in EP2-deficient mice. Ex
      vivo stimulation of peritoneal macrophages with LPS elicited proinflammatory
      responses that were dependent on EP2 signaling and that overlapped with in vivo
      plasma findings, suggesting that myeloid-lineage EP2 signaling is a major
      effector of innate immune responses. Conditional deletion of the EP2 receptor in
      myeloid lineage cells in Cd11bCre;EP2(lox/lox) mice attenuated plasma
      inflammatory responses and transmission of systemic inflammation to the brain was
      inhibited, with decreased hippocampal inflammatory gene expression and cerebral
      cortical levels of IL-6. Conditional deletion of EP2 significantly blunted
      microglial and astrocytic inflammatory responses to the neurotoxin MPTP and
      reduced striatal dopamine turnover. Suppression of microglial EP2 signaling also
      increased numbers of dopaminergic (DA) neurons in the substantia nigra
      independent of MPTP treatment, suggesting that microglial EP2 may influence
      development or survival of DA neurons. Unbiased microarray analysis of microglia
      isolated from adult Cd11bCre;EP2(lox/lox) and control mice demonstrated a broad
      downregulation of inflammatory pathways with ablation of microglial EP2 receptor.
      Together, these data identify a cell-specific proinflammatory role for
      macrophage/microglial EP2 signaling in innate immune responses systemically and
      in brain.

PMID- 24089507
TI  - Gene-environment processes linking peer victimization and physical health
      problems: a longitudinal twin study.
AB  - OBJECTIVE: This study examined whether (a) a genetic disposition for physical
      health problems increases the risk of peer victimization and (b) peer
      victimization interacts with genetic vulnerability in explaining physical health
      problems. METHODS: Participants were 167 monozygotic and 119 dizyogtic twin
      pairs. Physical symptoms were assessed in early childhood and early adolescence.
      Peer victimization was assessed in middle childhood. RESULTS: Genetic
      vulnerability for physical health problems in early childhood was unrelated to
      later peer victimization, but genetic vulnerability for physical health problems
      during early adolescence increased the risk of victimization. Victimization did
      not interact with genetic factors in predicting physical symptoms. Environmental,
      not genetic, factors had the greatest influence on the development of physical
      symptoms in victims. CONCLUSION: Genetic vulnerability for physical health
      problems in early adolescence increases the risk of peer victimization. Whether
      victims suffer a further increase in physical symptoms depends on the presence of
      protective environmental factors.

PMID- 24089508
TI  - Soluble factors secreted by T cells promote beta-cell proliferation.
AB  - Type 1 diabetes is characterized by infiltration of pancreatic islets with immune
      cells, leading to insulin deficiency. Although infiltrating immune cells are
      traditionally considered to negatively impact beta-cells by promoting their
      death, their contribution to proliferation is not fully understood. Here we
      report that islets exhibiting insulitis also manifested proliferation of beta
      cells that positively correlated with the extent of lymphocyte infiltration.
      Adoptive transfer of diabetogenic CD4(+) and CD8(+) T cells, but not B cells,
      selectively promoted beta-cell proliferation in vivo independent from the effects
      of blood glucose or circulating insulin or by modulating apoptosis. Complementary
      to our in vivo approach, coculture of diabetogenic CD4(+) and CD8(+) T cells with
      NOD.RAG1(-/-) islets in an in vitro transwell system led to a dose-dependent
      secretion of candidate cytokines/chemokines (interleukin-2 [IL-2], IL-6, IL-10,
      MIP-1alpha, and RANTES) that together enhanced beta-cell proliferation. These
      data suggest that soluble factors secreted from T cells are potential therapeutic
      candidates to enhance beta-cell proliferation in efforts to prevent and/or delay
      the onset of type 1 diabetes. 

PMID- 24089509
TI  - Impact of C-peptide preservation on metabolic and clinical outcomes in the
      Diabetes Control and Complications Trial.
AB  - The Diabetes Control and Complications Trial established that a stimulated C
      peptide concentration >=0.2 nmol/L at study entry among subjects with up to a 5
      year diabetes duration is associated with favorable metabolic and clinical
      outcomes over the subsequent 7 years of follow-up. Herein we further examine the
      association of both fasting and stimulated C-peptide numerical values with
      outcomes. In the intensive treatment group, for a 50% higher stimulated C-peptide
      on entry, such as from 0.10 to 0.15 nmol/L, HbA1c decreased by 0.07% (0.8
      mmol/mol; P = 0.0003), insulin dose decreased by 0.0276 units/kg/day (P <
      0.0001), hypoglycemia risk decreased by 8.2% (P < 0.0001), and the risk of
      sustained retinopathy was reduced by 25% (P = 0.0010), all in unadjusted
      analyses. Other than HbA1c, these effects remained significant after adjusting
      for the HbA1c on entry. While C-peptide was not significantly associated with the
      incidence of nephropathy, it was strongly associated with the albumin excretion
      rate. The fasting C-peptide had weaker associations with outcomes. As C-peptide
      decreased to nonmeasurable concentrations, the outcomes changed in a nearly
      linear manner, with no threshold or breakpoint. While preservation of stimulated
      C-peptide at >=0.2 nmol/L has clinically beneficial outcomes, so also does an
      increase in the concentration of C-peptide across the range of values. 

PMID- 24089510
TI  - Hepatocyte growth factor/c-Met signaling is required for beta-cell regeneration.
AB  - Hepatocyte growth factor (HGF) is a mitogen required for beta-cell replication
      during pregnancy. To determine whether HGF/c-Met signaling is required for beta
      cell regeneration, we characterized mice with pancreatic deletion of the HGF
      receptor, c-Met (PancMet KO mice), in two models of reduced beta-cell mass and
      regeneration: multiple low-dose streptozotocin (MLDS) and partial pancreatectomy
      (Ppx). We also analyzed whether HGF administration could accelerate beta-cell
      regeneration in wild-type (WT) mice after Ppx. Mouse islets obtained 7 days post
      Ppx displayed significantly increased c-Met, suggesting a potential role for
      HGF/c-Met in beta-cell proliferation in situations of reduced beta-cell mass.
      Indeed, adult PancMet KO mice displayed markedly reduced beta-cell replication
      compared with WT mice 7 days post-Ppx. Similarly, beta-cell proliferation was
      decreased in PancMet KO mice in the MLDS mouse model. The decrease in beta-cell
      proliferation post-Ppx correlated with a striking decrease in D-cyclin levels.
      Importantly, PancMet KO mice showed significantly diminished beta-cell mass,
      decreased glucose tolerance, and impaired insulin secretion compared with WT mice
      28 days post-Ppx. Conversely, HGF administration in WT Ppx mice further
      accelerated beta-cell regeneration. These results indicate that HGF/c-Met
      signaling is critical for beta-cell proliferation in situations of diminished
      beta-cell mass and suggest that activation of this pathway can enhance beta-cell
      regeneration. 

PMID- 24089511
TI  - Comparative effects of prolonged and intermittent stimulation of the glucagon
      like peptide 1 receptor on gastric emptying and glycemia.
AB  - Acute administration of glucagon-like peptide 1 (GLP-1) and its agonists slows
      gastric emptying, which represents the major mechanism underlying their
      attenuation of postprandial glycemic excursions. However, this effect may
      diminish during prolonged use. We compared the effects of prolonged and
      intermittent stimulation of the GLP-1 receptor on gastric emptying and glycemia.
      Ten healthy men received intravenous saline (placebo) or GLP-1 (0.8 pmol/kg ?
      min), as a continuous 24-h infusion ("prolonged"), two 4.5-h infusions separated
      by 20 h ("intermittent"), and a 4.5-h infusion ("acute") in a randomized, double
      blind, crossover fashion. Gastric emptying of a radiolabeled mashed potato meal
      was measured using scintigraphy. Acute GLP-1 markedly slowed gastric emptying.
      The magnitude of the slowing was attenuated with prolonged but maintained with
      intermittent infusions. GLP-1 potently diminished postprandial glycemia during
      acute and intermittent regimens. These observations suggest that short-acting GLP
      1 agonists may be superior to long-acting agonists when aiming specifically to
      reduce postprandial glycemic excursions in the treatment of type 2 diabetes. 

PMID- 24089512
TI  - Novel PEGylated basal insulin LY2605541 has a preferential hepatic effect on
      glucose metabolism.
AB  - The impact of the novel basal insulin LY2605541 (LY) on hepatic and nonhepatic
      glucose uptake (non-HGU) was evaluated. Conscious dogs underwent euglycemic
      clamps with tracer and hepatic balance measurements. Clamp period infusions were
      peripheral venous regular insulin (0.1 nmol ? kg(-1) ? h(-1) [control], n = 6) or
      LY (bolus [nmol/kg], continuous [nmol ? kg(-1) ? h(-1)]: 0.5, 0.5 [n = 6]; 0.375,
      0.375 [n = 5]; 0.25, 0.25 [n = 4]), somatostatin, and glucose, as well as
      intraportal glucagon (basal). During the clamp, the dogs switched from net
      hepatic glucose output to uptake (rates reached 2.1 +/- 1.2, 0.9 +/- 2.1, 8.6 +/-
      2.3, and 6.0 +/- 1.1 umol ? kg(-1) ? min(-1) within 5 h in control, LY0.25,
      LY0.375, and LY0.5, respectively). Non-HGU in LY increased less than in control;
      the ratio of change from basal in non-HGU to change in net hepatic glucose
      balance, calculated when glucose infusion rates (GIRs) were ~20 umol ? kg(-1) ?
      min(-1) in all groups, was higher in control (1.17 +/- 0.38) versus LY0.25 (0.39
      +/- 0.33), LY0.375 (-0.01 +/- 0.13), and LY0.5 (-0.09 +/- 0.07). Likewise, the
      change from baseline in glucose Rd-to-Ra ratio was greatest in control (1.4 +/-
      0.3 vs. 0.6 +/- 0.4, 0.5 +/- 0.2, and 0.6 +/- 0.2 in LY0.25, LY0.375, and LY0.5,
      respectively). In contrast to exogenously administered human insulin, LY
      demonstrated preferential hepatic effects, similar to endogenously secreted
      insulin. Therefore, the analog might reduce complications associated with current
      insulin therapy. 

PMID- 24089513
TI  - Contribution of endogenous glucagon-like peptide 1 to glucose metabolism after
      Roux-en-Y gastric bypass.
AB  - The contribution of elevated glucagon-like peptide 1 (GLP-1) to postprandial
      glucose metabolism after Roux-en-Y gastric bypass (RYGB) has been the subject of
      uncertainty. We used exendin-9,39, a competitive antagonist of GLP-1, to examine
      glucose metabolism, islet hormone secretion, and gastrointestinal transit in
      subjects after RYGB and in matched control subjects. Subjects were studied in the
      presence or absence of exendin-9,39 infused at 300 pmol/kg/min. Exendin-9,39
      resulted in an increase in integrated postprandial glucose concentrations post
      RYGB (3.6 +/- 0.5 vs. 2.0 +/- 0.4 mol/6 h, P = 0.001). Exendin-9,39 decreased
      insulin concentrations (12.3 +/- 2.2 vs. 18.1 +/- 3.1 nmol/6 h, P = 0.002) and
      the beta-cell response to glucose (Total, 13 +/- 1 vs. 11 +/- 1 * 10(-9) min(-1),
      P = 0.01) but did not alter the disposition index (DI). In control subjects,
      exendin-9,39 also increased glucose (2.2 +/- 0.4 vs. 1.7 +/- 0.3 mol/6 h, P =
      0.03) without accompanying changes in insulin concentrations, resulting in an
      impaired DI. Post-RYGB, acceleration of stomach emptying during the first 30 min
      by exendin-9,39 did not alter meal appearance, and similarly, suppression of
      glucose production and stimulation of glucose disappearance were unaltered in
      RYGB subjects. These data indicate that endogenous GLP-1 has effects on glucose
      metabolism and on gastrointestinal motility years after RYGB. However, it remains
      uncertain whether this explains all of the changes after RYGB. 

PMID- 24089514
TI  - A smad signaling network regulates islet cell proliferation.
AB  - Pancreatic beta-cell loss and dysfunction are critical components of all types of
      diabetes. Human and rodent beta-cells are able to proliferate, and this
      proliferation is an important defense against the evolution and progression of
      diabetes. Transforming growth factor-beta (TGF-beta) signaling has been shown to
      affect beta-cell development, proliferation, and function, but beta-cell
      proliferation is thought to be the only source of new beta-cells in the adult.
      Recently, beta-cell dedifferentiation has been shown to be an important
      contributory mechanism to beta-cell failure. In this study, we tie together these
      two pathways by showing that a network of intracellular TGF-beta regulators,
      smads 7, 2, and 3, control beta-cell proliferation after beta-cell loss, and
      specifically, smad7 is necessary for that beta-cell proliferation. Importantly,
      this smad7-mediated proliferation appears to entail passing through a transient,
      nonpathologic dedifferentiation of beta-cells to a pancreatic polypeptide-fold
      hormone-positive state. TGF-beta receptor II appears to be a receptor important
      for controlling the status of the smad network in beta-cells. These studies
      should help our understanding of properly regulated beta-cell replication. 

PMID- 24089515
TI  - Posttranslational modification of HLA-DQ binding islet autoantigens in type 1
      diabetes.
AB  - Posttranslational modification (PTM) of islet autoantigens can cause lack of
      central tolerance in type 1 diabetes (T1D). Tissue transglutaminase (tTG),
      involved in PTM of gluten antigens in celiac disease, creates negatively charged
      peptides favored by T1D-predisposing HLA-DQ molecules, offering an attractive
      candidate modifying islet autoantigens in T1D. The highly predisposing HLA
      DQ8cis/trans molecules share preferences for negatively charged peptides, as well
      as distinct peptide-binding characteristics that distinguish their peptide
      binding repertoire. We screened islet autoantigens with the tTG substrate motif
      for candidate-modified epitopes binding to HLA-DQ8cis/trans and identified 31
      candidate islet epitopes. Deamidation was confirmed for 28 peptides (90%). Two of
      these epitopes preferentially bound to HLA-DQ8cis and six to HLA-DQ8trans upon
      deamidation, whereas all other peptides bound equally to HLA-DQ8cis/trans. HLA
      DQ8cis-restricted T cells from a new-onset T1D patient could only be generated
      against a deamidated proinsulin peptide, but cross-reacted with native proinsulin
      peptide upon restimulation. The rate of T-cell autoreactivity in recent-onset T1D
      patients extended from 42% to native insulin to 68% adding responses to modified
      proinsulin, versus 20% and 37% respectively, in healthy donors. Most patients
      responded by interferon-gamma, whereas most healthy donors produced interleukin
      10 only. Thus, T-cell autoreactivity exists to modified islet epitopes that
      differs in quality and quantity between patients and healthy donors. 

PMID- 24089516
TI  - The association between circulating lipoprotein(a) and type 2 diabetes: is it
      causal?
AB  - Epidemiological evidence supports a direct and causal association between
      lipoprotein(a) [Lp(a)] levels and coronary risk, but the nature of the
      association between Lp(a) levels and risk of type 2 diabetes (T2D) is unclear. In
      this study, we assessed the association of Lp(a) levels with risk of incident T2D
      and tested whether Lp(a) levels are causally linked to T2D. We analyzed data on
      18,490 participants from the European Prospective Investigation of Cancer (EPIC)
      Norfolk cohort that included adults aged 40-79 years at baseline 1993-1997.
      During an average 10 years of follow-up, 593 participants developed incident T2D.
      Cox regression models were used to estimate the association between Lp(a) levels
      and T2D. In Mendelian randomization analyses, based on EPIC-Norfolk combined with
      DIAbetes Genetics Replication And Meta-analysis data involving a total of 10,088
      diabetes case participants and 68,346 control participants, we used a genetic
      variant (rs10455872) as an instrument to test whether the association between
      Lp(a) levels and T2D is causal. In adjusted analyses, there was an inverse
      association between Lp(a) levels and T2D: hazard ratio was 0.63 (95% CI 0.49
      0.81; P trend = 0.003) comparing the top versus bottom quintile of Lp(a). In EPIC
      Norfolk, a 1-SD increase in logLp(a) was associated with a lower risk of T2D
      (odds ratio [OR] 0.88 [95% CI: 0.80-0.95]). However, in Mendelian randomization
      analyses, a 1-SD increase in logLp(a) due to rs10455872, which explained 26.8% of
      the variability in Lp(a) levels, was not associated with risk of T2D (OR 1.03
      [0.96-1.10]; P = 0.41). These prospective findings demonstrate a strong inverse
      association of Lp(a) levels with risk of T2D. However, a genetic variant that
      elevated Lp(a) levels was not associated with risk of T2D, suggesting that
      elevated Lp(a) levels are not causally associated with a lower risk of T2D. 

PMID- 24089518
TI  - Basic properties of rotary dynamics of the molecular motor Enterococcus hirae V1
      ATPase.
AB  - V-ATPases are rotary molecular motors that generally function as proton pumps. We
      recently solved the crystal structures of the V1 moiety of Enterococcus hirae V
      ATPase (EhV1) and proposed a model for its rotation mechanism. Here, we
      characterized the rotary dynamics of EhV1 using single-molecule analysis
      employing a load-free probe. EhV1 rotated in a counterclockwise direction,
      exhibiting two distinct rotational states, namely clear and unclear, suggesting
      unstable interactions between the rotor and stator. The clear state was analyzed
      in detail to obtain kinetic parameters. The rotation rates obeyed Michaelis
      Menten kinetics with a maximal rotation rate (Vmax) of 107 revolutions/s and a
      Michaelis constant (Km) of 154 MUM at 26  degrees C. At all ATP concentrations
      tested, EhV1 showed only three pauses separated by 120 degrees /turn, and no
      substeps were resolved, as was the case with Thermus thermophilus V1-ATPase
      (TtV1). At 10 MUM ATP (<<Km), the distribution of the durations of the ATP
      waiting pause fit well with a single-exponential decay function. The second-order
      binding rate constant for ATP was 2.3 * 10(6) M(-1) s(-1). At 40 mM ATP (>>Km),
      the distribution of the durations of the catalytic pause was reproduced by a
      consecutive reaction with two time constants of 2.6 and 0.5 ms. These kinetic
      parameters were similar to those of TtV1. Our results identify the common
      properties of rotary catalysis of V1-ATPases that are distinct from those of F1
      ATPases and will further our understanding of the general mechanisms of rotary
      molecular motors.

PMID- 24089517
TI  - CB1 cannabinoid receptors couple to focal adhesion kinase to control insulin
      release.
AB  - Endocannabinoid signaling has been implicated in modulating insulin release from
      beta cells of the endocrine pancreas. beta Cells express CB1 cannabinoid
      receptors (CB1Rs), and the enzymatic machinery regulating anandamide and 2
      arachidonoylglycerol bioavailability. However, the molecular cascade coupling
      agonist-induced cannabinoid receptor activation to insulin release remains
      unknown. By combining molecular pharmacology and genetic tools in INS-1E cells
      and in vivo, we show that CB1R activation by endocannabinoids (anandamide and 2
      arachidonoylglycerol) or synthetic agonists acutely or after prolonged exposure
      induces insulin hypersecretion. In doing so, CB1Rs recruit Akt/PKB and
      extracellular signal-regulated kinases 1/2 to phosphorylate focal adhesion kinase
      (FAK). FAK activation induces the formation of focal adhesion plaques,
      multimolecular platforms for second-phase insulin release. Inhibition of
      endocannabinoid synthesis or FAK activity precluded insulin release. We conclude
      that FAK downstream from CB1Rs mediates endocannabinoid-induced insulin release
      by allowing cytoskeletal reorganization that is required for the exocytosis of
      secretory vesicles. These findings suggest a mechanistic link between increased
      circulating and tissue endocannabinoid levels and hyperinsulinemia in type 2
      diabetes. 

PMID- 24089519
TI  - Low selection pressure aids the evolution of cooperative ribozyme mutations in
      cells.
AB  - Understanding the evolution of functional RNA molecules is important for our
      molecular understanding of biology. Here we tested experimentally how two
      evolutionary parameters, selection pressure and recombination, influenced the
      evolution of an evolving RNA population. This was done using four parallel
      evolution experiments that employed low or gradually increasing selection
      pressure, and recombination events either at the end or dispersed throughout the
      evolution. As model system, a trans-splicing group I intron ribozyme was evolved
      in Escherichia coli cells over 12 rounds of selection and amplification,
      including mutagenesis and recombination. The low selection pressure resulted in
      higher efficiency of the evolved ribozyme populations, whereas differences in
      recombination did not have a strong effect. Five mutations were responsible for
      the highest efficiency. The first mutation swept quickly through all four
      evolving populations, whereas the remaining four mutations accumulated later and
      more efficiently under low selection pressure. To determine why low selection
      pressure aided this evolution, all evolutionary intermediates between the wild
      type and the 5-mutation variant were constructed, and their activities at three
      different selection pressures were determined. The resulting fitness profiles
      showed a high cooperativity among the four late mutations, which can explain why
      high selection pressure led to inefficient evolution. These results show
      experimentally how low selection pressure can benefit the evolution of
      cooperative mutations in functional RNAs. 

PMID- 24089520
TI  - Two novel Tau antibodies targeting the 396/404 region are primarily taken up by
      neurons and reduce Tau protein pathology.
AB  - Aggregated Tau proteins are hallmarks of Alzheimer disease and other tauopathies.
      Recent studies from our group and others have demonstrated that both active and
      passive immunizations reduce Tau pathology and prevent cognitive decline in
      transgenic mice. To determine the efficacy and safety of targeting the prominent
      396/404 region, we developed two novel monoclonal antibodies (mAbs) with distinct
      binding profiles for phospho and non-phospho epitopes. The two mAbs significantly
      reduced hyperphosphorylated soluble Tau in long term brain slice cultures without
      apparent toxicity, suggesting the therapeutic importance of targeting the 396/404
      region. In mechanistic studies, we found that neurons were the primary cell type
      that internalized the mAbs, whereas a small amount of mAbs was taken up by
      microglia cells. Within neurons, the two mAbs were highly colocalized with
      distinct pathological Tau markers, indicating their affinity toward different
      stages or forms of pathological Tau. Moreover, the mAbs were largely co-localized
      with endosomal/lysosomal markers, and partially co-localized with autophagy
      pathway markers. Additionally, the Fab fragments of the mAbs were able to enter
      neurons, but unlike the whole antibodies, the fragments were not specifically
      localized in pathological neurons. In summary, our Tau mAbs were safe and
      efficient to clear pathological Tau in a brain slice model. Fc-receptor-mediated
      endocytosis and the endosome/autophagosome/lysosome system are likely to have a
      critical role in antibody-mediated clearance of Tau pathology. 

PMID- 24089521
TI  - The leukemia-associated Mll-Ell oncoprotein induces fibroblast growth factor 2
      (Fgf2)-dependent cytokine hypersensitivity in myeloid progenitor cells.
AB  - The subset of acute myeloid leukemias (AML) with chromosomal translocations
      involving the MLL gene have a poor prognosis (referred to as 11q23-AML). The MLL
      fusion proteins that are expressed in 11q23-AML facilitate transcription of a set
      of HOX genes, including HOXA9 and HOXA10. Because Hox proteins are transcription
      factors, this suggests the possibility that Hox target genes mediate the adverse
      effects of MLL fusion proteins in leukemia. Identifying such Hox target genes
      might provide insights to the pathogenesis and treatment of 11q23-AML. In the
      current study we found that Mll-Ell (an MLL fusion protein) induced
      transcriptional activation of the FGF2 gene in a HoxA9- and HoxA10-dependent
      manner. FGF2 encodes fibroblast growth factor 2 (also referred to as basic
      fibroblast growth factor). Fgf2 influences proliferation and survival of
      hematopoietic stem cells and myeloid progenitor cells, and increased Fgf2
      expression has been described in AMLs. We determined that expression of Mll-Ell
      in myeloid progenitor cells resulted in autocrine production of Fgf2 and Fgf2
      dependent cytokine hypersensitivity. Therefore, our results implicated increased
      Fgf2 expression in progenitor proliferation and expansion in 11q23-AML. Because
      small molecule inhibitors of Fgf-receptors are in human clinical trials, this
      suggested a potential therapeutic approach to this treatment refractory leukemia.

PMID- 24089522
TI  - Impaired phosphorylation and ubiquitination by p70 S6 kinase (p70S6K) and Smad
      ubiquitination regulatory factor 1 (Smurf1) promote tribbles homolog 2 (TRIB2)
      stability and carcinogenic property in liver cancer.
AB  - Tribbles homolog 2 (TRIB2) is critical for both solid and non-solid malignancies.
      Recently, TRIB2 was identified as a liver cancer-specific Wnt/beta-catenin
      signaling downstream target and is functionally important for liver cancer cell
      survival and transformation. TRIB2 functions as a protein that interacts with E3
      ubiquitin ligases and thereby modulates protein stability of downstream
      effectors. However, the regulation underlying TRIB2 protein stability per se has
      not yet been reported. In this study, we found that TRIB2 was up-regulated and
      exhibited high stability in liver cancer cells compared with other cells. We
      performed a structure-function analysis of TRIB2 and identified a domain (amino
      acids 1-5) at the N terminus that interacted with the E3 ubiquitin ligase Smurf1
      and was critical for protein stability. Deletion of this domain extended TRIB2
      half-life time accompanied with a more significant malignant property compared
      with wild type TRIB2. Furthermore, Smurf1-mediated ubiquitination required
      phosphorylation of TRIB2 by p70 S6 kinase (p70S6K) via another domain (amino
      acids 69-85) that is also essential for correct TRIB2 subcellular localization.
      Mutation of Ser-83 diminished p70S6K-induced phosphorylation of TRIB2. Moreover,
      the high stability of TRIB2 may be due to the fact that both p70S6K and Smurf1
      were down-regulated and negatively correlated with TRIB2 expression in both liver
      cancer tissues and established liver cancer cell lines. Taken together, impaired
      phosphorylation and ubiquitination by p70S6K and Smurf1 increase the protein
      stability of TRIB2 in liver cancer and thus may be helpful in the development of
      diagnosis and treatment strategies against this malignant disease. 

PMID- 24089523
TI  - Extracellular signal-regulated kinase (ERK) phosphorylates histone deacetylase 6
      (HDAC6) at serine 1035 to stimulate cell migration.
AB  - Histone deacetylase 6 (HDAC6) is well known for its ability to promote cell
      migration through deacetylation of its cytoplasmic substrates such as alpha
      tubulin. However, how HDAC6 itself is regulated to control cell motility remains
      elusive. Previous studies have shown that one third of extracellular signal
      regulated kinase (ERK) is associated with the microtubule cytoskeleton in cells.
      Yet, no connection between HDAC6 and ERK has been discovered. Here, for the first
      time, we reveal that ERK binds to and phosphorylates HDAC6 to promote cell
      migration via deacetylation of alpha-tubulin. We have identified two novel ERK
      mediated phosphorylation sites: threonine 1031 and serine 1035 in HDAC6. Both
      sites were phosphorylated by ERK1 in vitro, whereas Ser-1035 was phosphorylated
      in response to the activation of EGFR-Ras-Raf-MEK-ERK signaling pathway in vivo.
      HDAC6-null mouse embryonic fibroblasts rescued by the nonphosphorylation
      mimicking mutant displayed significantly reduced cell migration compared with
      those rescued by the wild type. Consistently, the nonphosphorylation mimicking
      mutant exerted lower tubulin deacetylase activity in vivo compared with the wild
      type. These data indicate that ERK/HDAC6-mediated cell motility is through
      deacetylation of alpha-tubulin. Overall, our results suggest that HDAC6-mediated
      cell migration could be governed by EGFR-Ras-Raf-MEK-ERK signaling. 

PMID- 24089524
TI  - Nicotine induces the up-regulation of the alpha7-nicotinic receptor (alpha7
      nAChR) in human squamous cell lung cancer cells via the Sp1/GATA protein pathway.
AB  - Nicotine, the addictive component of cigarettes, promotes lung cancer
      proliferation via the alpha7-nicotinic acetylcholine receptor (alpha7-nAChR)
      subtype. The present manuscript explores the effect of nicotine exposure on
      alpha7-nAChR levels in squamous cell carcinoma of the lung (SCC-L) in vitro and
      in vivo. Nicotine (at concentrations present in the plasma of average smokers)
      increased alpha7-nAChR levels in human SCC-L cell lines. Nicotine-induced up
      regulation of alpha7-nAChR was confirmed in vivo by chicken chorioallantoic
      membrane models. We also observed that the levels of alpha7-nAChR in human SCC-L
      tumors (isolated from patients who are active smokers) correlated with their
      smoking history. Nicotine increased the levels of alpha7-nAChR mRNA and alpha7
      nAChR transcription in human SCC-L cell lines and SCC-L tumors. Nicotine-induced
      up-regulation of alpha7-nAChR required GATA4 and GATA6. ChIP assays showed that
      nicotine induced the binding of GATA4 or GATA6 to Sp1 on the alpha7-nAChR
      promoter, thereby inducing its transcription and increasing its levels in human
      SCC-L. Our data are clinically relevant because SCC-L patients smoked for decades
      before being diagnosed with cancer. It may be envisaged that continuous exposure
      to nicotine (in such SCC-L patients) causes up-regulation of alpha7-nAChRs, which
      facilitates tumor growth and progression. Our results will also be relevant to
      many SCC-L patients exposed to nicotine via second-hand smoke, electronic
      cigarettes, and patches or gums to quit smoking. 

PMID- 24089525
TI  - A key role for Plasmodium subtilisin-like SUB1 protease in egress of malaria
      parasites from host hepatocytes.
AB  - In their mammalian host, Plasmodium parasites have two obligatory intracellular
      development phases, first in hepatocytes and subsequently in erythrocytes. Both
      involve an orchestrated process of invasion into and egress from host cells. The
      Plasmodium SUB1 protease plays a dual role at the blood stage by enabling egress
      of the progeny merozoites from the infected erythrocyte and priming merozoites
      for subsequent erythrocyte invasion. Here, using conditional mutagenesis in P.
      berghei, we show that SUB1 plays an essential role at the hepatic stage. Stage
      specific sub1 invalidation during prehepatocytic development showed that SUB1
      deficient parasites failed to rupture the parasitophorous vacuole membrane and to
      egress from hepatocytes. Furthermore, mechanically released parasites were not
      adequately primed and failed to establish a blood stage infection in vivo. The
      critical involvement of SUB1 in both pre-erythrocytic and erythrocytic
      developmental phases qualifies SUB1 as an attractive multistage target for
      prophylactic and therapeutic anti-Plasmodium intervention strategies. 

PMID- 24089526
TI  - Targeting aberrant glutathione metabolism to eradicate human acute myelogenous
      leukemia cells.
AB  - The development of strategies to eradicate primary human acute myelogenous
      leukemia (AML) cells is a major challenge to the leukemia research field. In
      particular, primitive leukemia cells, often termed leukemia stem cells, are
      typically refractory to many forms of therapy. To investigate improved strategies
      for targeting of human AML cells we compared the molecular mechanisms regulating
      oxidative state in primitive (CD34(+)) leukemic versus normal specimens. Our data
      indicate that CD34(+) AML cells have elevated expression of multiple glutathione
      pathway regulatory proteins, presumably as a mechanism to compensate for
      increased oxidative stress in leukemic cells. Consistent with this observation,
      CD34(+) AML cells have lower levels of reduced glutathione and increased levels
      of oxidized glutathione compared with normal CD34(+) cells. These findings led us
      to hypothesize that AML cells will be hypersensitive to inhibition of glutathione
      metabolism. To test this premise, we identified compounds such as parthenolide
      (PTL) or piperlongumine that induce almost complete glutathione depletion and
      severe cell death in CD34(+) AML cells. Importantly, these compounds only induce
      limited and transient glutathione depletion as well as significantly less
      toxicity in normal CD34(+) cells. We further determined that PTL perturbs
      glutathione homeostasis by a multifactorial mechanism, which includes inhibiting
      key glutathione metabolic enzymes (GCLC and GPX1), as well as direct depletion of
      glutathione. These findings demonstrate that primitive leukemia cells are
      uniquely sensitive to agents that target aberrant glutathione metabolism, an
      intrinsic property of primary human AML cells. 

PMID- 24089528
TI  - Arabidopsis thaliana AMY3 is a unique redox-regulated chloroplastic alpha
      amylase.
AB  - alpha-Amylases are glucan hydrolases that cleave alpha-1,4-glucosidic bonds in
      starch. In vascular plants, alpha-amylases can be classified into three
      subfamilies. Arabidopsis has one member of each subfamily. Among them, only
      AtAMY3 is localized in the chloroplast. We expressed and purified AtAMY3 from
      Escherichia coli and carried out a biochemical characterization of the protein to
      find factors that regulate its activity. Recombinant AtAMY3 was active toward
      both insoluble starch granules and soluble substrates, with a strong preference
      for beta-limit dextrin over amylopectin. Activity was shown to be dependent on a
      conserved aspartic acid residue (Asp(666)), identified as the catalytic
      nucleophile in other plant alpha-amylases such as the barley AMY1. AtAMY3
      released small linear and branched glucans from Arabidopsis starch granules, and
      the proportion of branched glucans increased after the predigestion of starch
      with a beta-amylase. Optimal rates of starch digestion in vitro was achieved when
      both AtAMY3 and beta-amylase activities were present, suggesting that the two
      enzymes work synergistically at the granule surface. We also found that AtAMY3
      has unique properties among other characterized plant alpha-amylases, with a pH
      optimum of 7.5-8, appropriate for activity in the chloroplast stroma. AtAMY3 is
      also redox-regulated, and the inactive oxidized form of AtAMY3 could be
      reactivated by reduced thioredoxins. Site-directed mutagenesis combined with mass
      spectrometry analysis showed that a disulfide bridge between Cys(499) and
      Cys(587) is central to this regulation. This work provides new insights into how
      alpha-amylase activity may be regulated in the chloroplast. 

PMID- 24089527
TI  - Caveolin-1 interacts with Derlin-1 and promotes ubiquitination and degradation of
      cyclooxygenase-2 via collaboration with p97 complex.
AB  - Caveolin-1 (Cav-1) interacts with and mediates protein trafficking and various
      cellular functions. Derlin-1 is a candidate for the retrotranslocation channel of
      endoplasmic reticulum proteins. However, little is known about how Derlin-1
      mediates glycosylated protein degradation. Here, we identified Cav-1 as a key
      player in Derlin-1- and p97-mediated cyclooxygenase 2 (COX-2) ubiquitination and
      degradation. Derlin-1 augmented the interaction of Cav-1 and COX-2 and mediated
      the degradation of COX-2 in a COX-2 C terminus-dependent manner. Suppression of
      Cav-1 decreased the ubiquitination of COX-2, and mutation of Asn-594 to Ala to
      disrupt N-glycosylation at the C terminus of COX-2 reduced the interaction of COX
      2 with Cav-1 but not Derlin-1. Moreover, suppression of p97 increased the
      ubiquitination of COX-2 and up-regulated COX-2 but not COX-1. Cav-1 enhanced the
      interaction of p97 with Ufd1 and Derlin-1 and collaborated with p97 to interact
      with COX-2. Cav-1 may be a cofactor in the interaction of Derlin-1 and N
      glycosylated COX-2 and may facilitate Derlin-1- and p97 complex-mediated COX-2
      ubiquitination, retrotranslocation, and degradation. 

PMID- 24089529
TI  - The importance of the 45 S ribosomal small subunit-related complex for
      mitochondrial translation in Trypanosoma brucei.
AB  - The mitochondrial 45 S SSU* complex in Trypanosoma brucei contains the 9 S SSU
      ribosomal RNA, a set of SSU ribosomal proteins, several pentatricopeptide repeat
      (PPR) proteins, and proteins not typically found in ribosomes, including
      rhodanese domain protein (Rhod) and a 200-kDa coiled-coil protein. To investigate
      the function of this complex, PPR29, Rhod, 200-kDa protein, and mitochondrial
      ribosomal protein S17 were knocked down by RNAi in procyclic T. brucei. A growth
      retardation phenotype, a reduction in the amount of the 45 S SSU* complexes, and
      the preferential inhibition of synthesis of the cytochrome c oxidase subunit I
      over apocytochrome b were observed as early as day 2 postinduction of RNAi. On
      the contrary, the down-regulation of mitochondrial ribosomal protein L3
      drastically reduced the amount of the large subunit and indiscriminately
      inhibited mitochondrial translation. The relative amounts of translation
      competent, long poly(AU)-tailed cytochrome c oxidase subunit I and edited
      apocytochrome b mRNAs were selectively reduced by ablation of the 45 S SSU*
      complex. The formation of the 80 S translation complexes, identified by
      association of the long-tailed mRNAs with the mitoribosomes, was also disrupted.
      On the other hand, the relative amount of long-tailed edited RPS12 mRNA was not
      substantially affected, and there was no noticeable effect on the RPS12
      translation complexes. In bloodstream trypanosomes, the amount of the 45 S
      complexes was drastically reduced compared with procyclics. We propose that the
      45 S SSU* complex represents a factor required for normal mitochondrial
      translation that may have selective effects on different mRNAs. 

PMID- 24089530
TI  - Proteome variations in pancreatic stellate cells upon stimulation with
      proinflammatory factors.
AB  - Pancreatic stellate cells are key mediators in chronic pancreatitis and play a
      central role in the development of pancreatic fibrosis, stromal formation, and
      progression of pancreatic cancer. This study was aimed at investigating molecular
      changes at the level of the proteome that are associated with the activation of
      pancreatic stellate cells by proinflammatory factors, namely TNF-alpha, FGF2,
      IL6, and chemokine (C-C motif) ligand 4 (CCL4). They were added individually to
      cells growing in serum-free medium next to controls in medium supplemented with
      serum, thus containing a mixture of them all, or in serum-free medium alone.
      Variations were detected by means of a microarray of 810 antibodies targeting
      relevant proteins. All tested factors triggered increased proliferation and
      migration. Further analysis showed that TNF-alpha is the prime factor responsible
      for the activation of pancreatic stellate cells. CCL4 is associated with cellular
      neovascularization, whereas FGF2 and IL6 induction led to better cellular
      survival and decreased apoptotic activity of the stellate cells. The identified
      direct effects of individual cytokines on human pancreatic stellate cells provide
      new insights about their contribution to pancreatic cancer promotion. 

PMID- 24089531
TI  - NDUFAF7 methylates arginine 85 in the NDUFS2 subunit of human complex I.
AB  - Complex I (NADH ubiquinone oxidoreductase) in mammalian mitochondria is an L
      shaped assembly of 44 subunits. One arm is embedded in the inner membrane with
      the other protruding ~100 A into the matrix of the organelle. The extrinsic arm
      contains binding sites for NADH and the primary electron acceptor FMN, and it
      provides a scaffold for seven iron-sulfur clusters that form an electron pathway
      linking FMN to the terminal electron acceptor, ubiquinone, which is bound in the
      region of the junction between the arms. The membrane arm contains four
      antiporter-like domains, probably energetically coupled to the quinone site and
      involved in pumping protons from the matrix into the intermembrane space
      contributing to the proton motive force. Complex I is put together from
      preassembled subcomplexes. Their compositions have been characterized partially,
      and at least 12 extrinsic assembly factor proteins are required for the assembly
      of the complex. One such factor, NDUFAF7, is predicted to belong to the family of
      S-adenosylmethionine-dependent methyltransferases characterized by the presence
      in their structures of a seven-beta-strand protein fold. In the present study,
      the presence of NDUFAF7 in the mitochondrial matrix has been confirmed, and it
      has been demonstrated that it is a protein methylase that symmetrically
      dimethylates the omega-N(G),N(G') atoms of residue Arg-85 in the NDUFS2 subunit
      of complex I. This methylation step occurs early in the assembly of complex I and
      probably stabilizes a 400-kDa subcomplex that forms the initial nucleus of the
      peripheral arm and its juncture with the membrane arm. 

PMID- 24089532
TI  - Expression and regulatory effects of murine Schlafen (Slfn) genes in malignant
      melanoma and renal cell carcinoma.
AB  - There is emerging evidence that the IFN-inducible family of Slfn genes and
      proteins play important roles in cell cycle progression and control of cellular
      proliferation, but the precise functional roles of different Slfn members in the
      regulation of tumorigenesis remain unclear. In the present study, we undertook a
      systematic analysis on the expression and functional relevance of different mouse
      Slfn genes in malignant melanoma and renal cell carcinoma cells. Our studies
      demonstrate that several mouse Slfn genes are up-regulated in response to IFN
      treatment of mouse melanoma and renal cell carcinoma cells, including Slfn1,
      Slfn2, Slfn4, Slfn5, and Slfn8. Our data show that Slfn2 and Slfn3 play essential
      roles in the control of mouse malignant melanoma cell proliferation and/or
      anchorage-independent growth, suggesting key and non-overlapping roles for these
      genes in the control of malignant melanoma tumorigenesis. In renal cell carcinoma
      cells, in addition to Slfn2 and Slfn3, Slfn5 also exhibits important
      antineoplastic effects. Altogether, our findings indicate important functions for
      distinct mouse Slfn genes in the control of tumorigenesis and provide evidence
      for differential involvement of distinct members of this gene family in
      controlling tumorigenesis. They also raise the potential of future therapeutic
      approaches involving modulation of expression of members of this family of genes
      in malignant melanoma and renal cell carcinoma. 

PMID- 24089533
TI  - Enhanced expression of fucosyl GA1 in the digestive tract of immune-deficient
      scid, nude and pIgR(-/-) mice.
AB  - Fucosylation of GA1 in murine intestinal epithelia occurs through transcriptional
      induction of alpha1,2-fucosyltransferase along with bacterial infection, but the
      mechanism has not been clearly characterized as to whether it is induced as a
      result of an immune response to bacteria or of genetic manipulation of the host
      by bacteria. Accordingly, we analysed the expression of fucosyl GA1 (FGA1) and
      fucosyltransferase activity in the digestive tracts of immune-deficient scid,
      nude and pIgR(-/-) mice. In comparison with those in control mice bred under the
      same SPF circumstances, the amount of FGA1 and the alpha1,2-fucosyltransferase
      activity were significantly increased in the immune-deficient mice, indicating
      that the immune system is not involved in induction of the alpha1,2
      fucosyltransferase gene. Reflecting the enhanced synthesis of FGA1, the total
      amounts of FGA1 in the intestinal contents of immune-deficient mice were higher
      than those in control mice. Also, the major faecal bacteria grown on a MRS agar
      plate were different in immune-deficient and control mice as follows,
      Lactobacillus murinus for scid and pIgR(-/-) mice, and Lactobacillus johnsonii
      for their control, and Enterococcus faecalis for nude mice and Lactococcus
      garvieae for the control, indicating that an alteration in the intestinal
      lactobacilli is partly involved in the induction of alpha1,2-fucosyltransferase. 

PMID- 24089534
TI  - The relative and combined ability of high-sensitivity cardiac troponin T and N
      terminal pro-B-type natriuretic peptide to predict cardiovascular events and
      death in patients with type 2 diabetes.
AB  - OBJECTIVE Current methods of risk stratification in patients with type 2 diabetes
      are suboptimal. The current study assesses the ability of N-terminal pro-B-type
      natriuretic peptide (NT-proBNP) and high-sensitivity cardiac troponin T (hs-cTnT)
      to improve the prediction of cardiovascular events and death in patients with
      type 2 diabetes. RESEARCH DESIGN AND METHODS A nested case-cohort study was
      performed in 3,862 patients who participated in the Action in Diabetes and
      Vascular Disease: Preterax and Diamicron Modified Release Controlled Evaluation
      (ADVANCE) trial. RESULTS Seven hundred nine (18%) patients experienced a major
      cardiovascular event (composite of cardiovascular death, nonfatal myocardial
      infarction, or nonfatal stroke) and 706 (18%) died during a median of 5 years of
      follow-up. In Cox regression models, adjusting for all established risk
      predictors, the hazard ratio for cardiovascular events for NT-proBNP was 1.95 per
      1 SD increase (95% CI 1.72, 2.20) and the hazard ratio for hs-cTnT was 1.50 per 1
      SD increase (95% CI 1.36, 1.65). The hazard ratios for death were 1.97 (95% CI
      1.73, 2.24) and 1.52 (95% CI 1.37, 1.67), respectively. The addition of either
      marker improved 5-year risk classification for cardiovascular events (net
      reclassification index in continuous model, 39% for NT-proBNP and 46% for hs
      cTnT). Likewise, both markers greatly improved the accuracy with which the 5-year
      risk of death was predicted. The combination of both markers provided optimal
      risk discrimination. CONCLUSIONS NT-proBNP and hs-cTnT appear to greatly improve
      the accuracy with which the risk of cardiovascular events or death can be
      estimated in patients with type 2 diabetes. 

PMID- 24089535
TI  - ST-segment elevation myocardial infarction in women with type 2 diabetes.
AB  - OBJECTIVE: To evaluate the effect of type 2 diabetes on the clinical course and
      prognosis of women with ST-segment elevation myocardial infarction (STEMI) and
      diabetes. RESEARCH DESIGN AND METHODS: A total of 26,035 consecutive patients
      with STEMI who were hospitalized in 456 hospitals in Poland during 1 year were
      analyzed. The data were obtained from the Polish Registry of Acute Coronary
      Syndromes (PL-ACS). RESULTS: Type 2 diabetes occurred more frequently in women
      than in men (28 vs. 16.6%; P < 0.0001). The proportion of women was larger among
      patients with diabetes (47.1 vs. 31.3%; P < 0.0001), and compared with women
      without diabetes, diabetic women had worse clinical profiles. Women with diabetes
      were most frequently treated conservatively. Both women and men with diabetes had
      significantly more advanced atherosclerotic lesions than women without diabetes.
      Women with diabetes had the highest in-hospital, 6-month, and 1-year mortality
      rates. Multivariate analysis indicated that type 2 diabetes was a significant
      independent risk factor for in-hospital and 1-year mortality in women with STEMI.
      Primary percutaneous coronary intervention (pPCI) was a significant factor
      associated with the decreased 1-year mortality in women without diabetes.
      CONCLUSIONS: Type 2 diabetes was a significant independent risk factor for in
      hospital and 1-year mortality in women with STEMI. Women with diabetes had the
      poorest early and 1-year prognoses after STEMI when compared with women without
      diabetes and men with diabetes. Although pPCI improves the long-term prognosis of
      women with diabetes, it is used less frequently than in women without diabetes or
      men with diabetes.

PMID- 24089536
TI  - Hypoglycemia associated with hospitalization and adverse events in older people:
      population-based cohort study.
AB  - OBJECTIVE: Little is known about the prognostic impact of hypoglycemia associated
      with hospitalization. We hypothesized that hospitalized hypoglycemia would be
      associated with increased long-term morbidity and mortality, irrespective of
      diabetes status. RESEARCH DESIGN AND METHODS: We undertook a cohort study using
      linked administrative health care and laboratory databases in Alberta, Canada.
      From 1 January 2004 to 31 March 2009, we included all outpatients 66 years of age
      and older who had at least one serum creatinine and one A1C measured. To examine
      the independent association between hospitalized hypoglycemia and all-cause
      mortality, we used time-varying Cox proportional hazards (adjusted hazard ratio
      [aHR]), and for all-cause hospitalizations, we used Poisson regression (adjusted
      incidence rate ratio [aIRR]). RESULTS: The cohort included 85,810 patients: mean
      age 75 years, 51% female, and 50% had diabetes defined by administrative data.
      Overall, 440 patients (0.5%) had severe hypoglycemia associated with
      hospitalization and most (93%) had diabetes. During 4 years of follow-up, 16,320
      (19%) patients died. Hospitalized hypoglycemia was independently associated with
      increased mortality (60 vs. 19% mortality for no hypoglycemia; aHR 2.55 [95% CI
      2.25-2.88]), and this increased in a dose-dependent manner (aHR no hypoglycemia =
      1.0 vs. one episode = 2.49 vs. one or more = 3.78, P trend <0.001). Hospitalized
      hypoglycemia was also independently associated with subsequent hospitalizations
      (aIRR no hypoglycemia = 1.0 vs. one episode = 1.90 vs. one or more = 2.61, P
      trend <0.001) and recurrent hypoglycemia (aHR no hypoglycemia = 1.0 vs. one
      episode = 2.45 vs. one or more = 9.66, P trend <0.001). CONCLUSIONS: Older people
      who have an episode of hospitalized hypoglycemia are easily identified and at
      substantially increased risk of morbidity and mortality.

PMID- 24089537
TI  - Association between hyperglycemia at admission during hospitalization for acute
      myocardial infarction and subsequent diabetes: insights from the veterans
      administration cardiac care follow-up clinical study.
AB  - OBJECTIVE: Among patients with acute myocardial infarction (AMI) without known
      diabetes, hyperglycemia at admission is common and associated with worse
      outcomes. It may represent developing diabetes, but this association is unclear.
      Therefore, we examined the association between hyperglycemia (>=140 mg/dL) at
      admission and evidence of diabetes among patients with AMI without known diabetes
      within 6 months of their hospitalization. RESEARCH DESIGN AND METHODS: We studied
      a national cohort of consecutive patients with AMI without known diabetes
      presenting at 127 Veterans Affairs hospitals between October 2005 and March 2011.
      Evidence of diabetes either at discharge or in the following 6 months was
      ascertained using diagnostic codes, medication prescriptions, and/or elevated
      hemoglobin A1c. Association between hyperglycemia at admission and evidence of
      diabetes was evaluated using regression modeling. RESULTS: Among 10,499 patients
      with AMI without known diabetes, 98% were men and 1,761 (16.8%) had hyperglycemia
      at admission. Within 6 months following their index hospitalization, 208 patients
      (11.8%) with hyperglycemia at admission had evidence of diabetes compared with
      443 patients (5.1%) without hyperglycemia at admission (P < 0.001). After
      multivariable adjustment, hyperglycemia at admission was significantly associated
      with subsequent diabetes odds ratio 2.56 (95% CI 2.15-3.06). Among those with new
      evidence of diabetes, 41% patients (267 of 651) had a hemoglobin A1c >=6.5%
      without accompanying diagnostic codes or medication prescriptions, suggesting
      they had unrecognized diabetes. CONCLUSIONS: Hyperglycemia at admission occurred
      in one of six patients with AMI without known diabetes and was significantly
      associated with new evidence of diabetes in the 6 months following
      hospitalization. In addition, two of five patients with evidence of diabetes were
      potentially unrecognized. Accordingly, diabetes-screening programs for
      hyperglycemic patients with AMI may be an important component of optimal care.

PMID- 24089538
TI  - Long-term outcomes of Japanese type 2 diabetic patients with biopsy-proven
      diabetic nephropathy.
AB  - OBJECTIVE: We evaluated the structural-functional relationships and the
      prognostic factors for renal events, cardiovascular events, and all-cause
      mortality in type 2 diabetic patients with biopsy-proven diabetic nephropathy.
      RESEARCH DESIGN AND METHODS: Japanese type 2 diabetic patients with biopsy-proven
      diabetic nephropathy (n = 260) were enrolled. Patients were stratified by
      albuminuria (proteinuria) and estimated glomerular filtration rate (eGFR) at the
      time of renal biopsy. The outcomes were the first occurrence of renal events
      (requirement of dialysis or a 50% decline in eGFR from baseline), cardiovascular
      events (cardiovascular death, nonfatal myocardial infarction, coronary
      interventions, or nonfatal stroke), and all-cause mortality. RESULTS: The factors
      associated with albuminuria (proteinuria) regardless of eGFR were hematuria,
      diabetic retinopathy, low hemoglobin, and glomerular lesions. The factors
      associated with low eGFR regardless of albuminuria (proteinuria) were age and
      diffuse, nodular, tubulointerstitial, and vascular lesions. The glomerular,
      tubulointerstitial, and vascular lesions in patients with normoalbuminuria
      (normal proteinuria) and low eGFR were more advanced compared to those in
      patients with normoalbuminuria (normal proteinuria) and maintained eGFR. In
      addition, compared to patients with micro-/macroalbuminuria (mild/severe
      proteinuria) and low eGFR, their tubulointerstitial and vascular lesions were
      similar or more advanced in contrast to glomerular lesions. The mean follow-up
      period was 8.1 years. There were 118 renal events, 62 cardiovascular events, and
      45 deaths. The pathological determinants were glomerular lesions, interstitial
      fibrosis and tubular atrophy (IFTA), and arteriosclerosis for renal events,
      arteriosclerosis for cardiovascular events, and IFTA for all-cause mortality. The
      major clinical determinant for renal events and all-cause mortality was
      macroalbuminuria (severe proteinuria). CONCLUSIONS: Our study suggests that the
      characteristic pathological lesions as well as macroalbuminuria (severe
      proteinuria) were closely related to the long-term outcomes of biopsy-proven
      diabetic nephropathy in type 2 diabetes.

PMID- 24089539
TI  - Short leg length, a marker of early childhood deprivation, is associated with
      metabolic disorders underlying type 2 diabetes: the PROMISE cohort study.
AB  - OBJECTIVE: Short leg length, a marker of early childhood deprivation, has been
      used in studies of the association of early life conditions with adult chronic
      disease risk. The objective of this study was to determine the cross-sectional
      associations of leg length with measures of insulin sensitivity and beta-cell
      function. RESEARCH DESIGN AND METHODS: Subjects (n = 462) at risk for type 2
      diabetes were recruited into the PROspective Metabolism and ISlet cell Evaluation
      (PROMISE) longitudinal cohort. Leg length was calculated from sitting and
      standing height at the 3-year clinical examination. Glucose tolerance status was
      determined using an oral glucose tolerance test. Insulin sensitivity was assessed
      using homeostasis model assessment of insulin resistance (HOMA-IR) and the
      Matsuda insulin sensitivity index (ISI), while the insulinogenic index over HOMA
      IR (IGI/IR) and the insulin secretion sensitivity index 2 (ISSI-2) determined
      beta-cell function. Multiple linear regression analysis was conducted, adjusting
      for covariates including age, sex, ethnicity, family history of diabetes, waist,
      and weight. RESULTS: Leg length and leg-to-height ratio were significantly
      associated with HOMA-IR (beta = -0.037, beta = -10.49, respectively; P < 0.0001),
      ISI (beta = 0.035, beta = 8.83, respectively; P < 0.0001), IGI/IR (beta = 0.021,
      P < 0.05; beta = 7.60, P < 0.01, respectively), and ISSI-2 (beta = 0.01, P <
      0.03; beta = 3.34, P < 0.01, respectively) after adjustment for covariates. The
      association of shorter leg length with lower insulin sensitivity was most evident
      for those with high waist circumferences. CONCLUSIONS: Shorter legs were
      independently associated with lower insulin sensitivity and beta-cell function,
      suggesting that early childhood deprivation may increase the risk of developing
      diabetes.

PMID- 24089541
TI  - External validation of the UKPDS risk engine in incident type 2 diabetes: a need
      for new type 2 diabetes-specific risk equations.
AB  - OBJECTIVE: To evaluate the performance of the UK Prospective Diabetes Study Risk
      Engine (UKPDS-RE) for predicting the 10-year risk of cardiovascular disease end
      points in an independent cohort of U.K. patients newly diagnosed with type 2
      diabetes. RESEARCH DESIGN AND METHODS: This was a retrospective cohort study
      using routine health care data collected between April 1998 and October 2011 from
      ~350 U.K. primary care practices contributing to the Clinical Practice Research
      Datalink (CPRD). Participants comprised 79,966 patients aged between 35 and 85
      years (388,269 person-years) with 4,984 cardiovascular events. Four outcomes were
      evaluated: first diagnosis of coronary heart disease (CHD), stroke, fatal CHD,
      and fatal stroke. RESULTS: Accounting for censoring, the observed versus
      predicted 10-year event rates were as follows: CHD 6.1 vs. 16.5%, fatal CHD 1.9
      vs. 10.1%, stroke 7.0 vs. 10.1%, and fatal stroke 1.7 vs. 1.6%, respectively. The
      UKPDS-RE showed moderate discrimination for all four outcomes, with the
      concordance index values ranging from 0.65 to 0.78. CONCLUSIONS: The UKPDS stroke
      equations showed calibration ranging from poor to moderate; however, the CHD
      equations showed poor calibration and considerably overestimated CHD risk. There
      is a need for revised risk equations in type 2 diabetes.

PMID- 24089540
TI  - Association of hypoglycemic treatment regimens with cardiovascular outcomes in
      overweight and obese subjects with type 2 diabetes: a substudy of the SCOUT
      trial.
AB  - OBJECTIVE: To assess the association of hypoglycemic treatment regimens with
      cardiovascular adverse events and mortality in a large population of type 2
      diabetic patients at increased cardiovascular risk. RESEARCH DESIGN AND METHODS:
      This analysis included 8,192 overweight patients with type 2 diabetes from the
      Sibutramine Cardiovascular Outcomes (SCOUT) trial randomized to lifestyle
      intervention with or without sibutramine for up to 6 years. Patients were grouped
      according to hypoglycemic treatment at baseline. The primary end point was the
      time from randomization to the first occurrence of a primary outcome event (POE),
      nonfatal myocardial infarction, nonfatal stroke, resuscitation after cardiac
      arrest, or cardiovascular death. Multivariable Cox proportional hazards
      regression models were used to assess the impact of antiglycemic treatment on POE
      and all-cause mortality. RESULTS: Treatments for type 2 diabetes were as follows:
      diet alone (n = 1,394 subjects), metformin monotherapy (n = 1,631), insulin
      monotherapy (n = 1,116), sulfonylurea monotherapy (n = 1,083), metformin plus
      sulfonylurea (n = 1,565), and metformin plus insulin (n = 1,000); 905 subjects
      experienced a POE and 708 died. Metformin monotherapy was associated with lower
      risk of POE than insulin (hazard ratio [HR], 0.74; 95% CI, 0.57-0.95; P = 0.02).
      Diet alone also was associated with lower risk of POE (HR, 0.65; 95% CI, 0.48
      0.87; P = 0.004). Metformin monotherapy also was associated with lower mortality
      (HR, 0.73; 95% CI, 0.54-0.99; P < 0.05), whereas no other monotherapies or
      combination therapies were significantly associated with POE or all-cause
      mortality compared with insulin as monotherapy. CONCLUSIONS: In obese patients
      with type 2 diabetes and high risk of cardiovascular disease, monotherapy with
      metformin or diet-only treatment was associated with lower risk of cardiovascular
      events than treatment with insulin.

PMID- 24089542
TI  - Needle-free jet injection of rapid-acting insulin improves early postprandial
      glucose control in patients with diabetes.
AB  - OBJECTIVE: Clamp studies have shown that the absorption and action of rapid
      acting insulin are faster with injection by a jet injector than with
      administration by conventional pen. To determine whether these pharmacokinetic
      changes also exist in patients with diabetes and benefit postprandial glucose
      control, we compared the pharmacologic profiles of insulin administration by jet
      injection versus conventional insulin pen after a standardized meal in patients
      with type 1 or type 2 diabetes. RESEARCH DESIGN AND METHODS: In a randomized,
      double-blind, double-dummy crossover study, 12 patients with type 1 diabetes and
      12 patients with type 2 diabetes received insulin aspart either by jet injection
      or by conventional pen, in both cases followed by a standardized meal. Blood was
      sampled for 6 h for determination of glucose and insulin levels to calculate
      pharmacologic profiles. RESULTS: Insulin administration by jet injection resulted
      in shorter time until peak plasma insulin level (51.3 +/- 6.4 vs. 91.9 +/- 10.2
      min; P = 0.003) and reduced hyperglycemic burden during the first hour (154.3 +/-
      20.8 vs. 196.3 +/- 18.4 mmol . min . L(-1); P = 0.041) compared with conventional
      administration. Jet injection did not, however, significantly reduce the
      hyperglycemic burden during the 5-h period thereafter. There was no indication
      that the jet injector performed differently in patients with type 1 and type 2
      diabetes. CONCLUSIONS: The considerably more rapid insulin absorption after
      administration by jet injector translated to a significant if modest decrease in
      postprandial hyperglycemia in patients with type 1 and type 2 diabetes. The
      improved early postprandial glucose control may specifically benefit patients who
      have difficulty in limiting postprandial glucose excursions.

PMID- 24089543
TI  - Microstructural brain tissue damage in metabolic syndrome.
AB  - OBJECTIVE: We investigated the association between metabolic syndrome risk
      factors and brain tissue integrity, as assessed by magnetic resonance imaging.
      RESEARCH DESIGN AND METHODS: From the Leiden Longevity Study, which is a
      community-based study of long-lived subjects, their offspring, and partners
      thereof, 130 subjects (61 men; mean age 66 years) were included. A metabolic
      syndrome score was computed by summing the individual number of components
      according to the Adult Treatment Panel III criteria. We performed linear and
      logistic regression analysis and used standardized beta-values to assess the
      association between metabolic syndrome and brain macrostructure (brain volume and
      white matter lesion load, lacunar infarcts, and cerebral microbleeds) and
      microstructure (mean magnetization transfer ratio [MTR], MTR histogram peak
      height, fractional anisotropy, and mean diffusivity [MD]). Linear and stepwise
      regression analysis was performed to identify the individual contribution of one
      metabolic syndrome parameter adjusting for the four other parameters. Models were
      adjusted for age, sex, and relation to long-lived family. RESULTS: Brain
      macrostructure was not associated with metabolic syndrome. In contrast, metabolic
      syndrome was associated with decreased gray (beta = -0.3 P = 0.001) and white
      matter peak height (beta = -0.3, P = 0.002) and increased gray matter MD (beta =
      0.2, P = 0.01, P = 0.01). Serum HDL cholesterol (beta = 0.22, P = 0.012),
      triglycerides (beta =-0.25, P = 0.002), BMI (beta =-0.2, P = 0.014), and
      diastolic blood pressure (beta = -0.17, P = 0.047, and beta = -0.23, P = 0.009,
      for gray and white matter, respectively) were independent factors in these
      changes in brain microstructure. CONCLUSIONS: In early manifest metabolic
      syndrome, brain tissue decline can be detected. Serum HDL cholesterol,
      triglycerides, BMI, and diastolic blood pressure were independent factors in
      brain tissue integrity.

PMID- 24089544
TI  - Perspectives from before and after the pediatric to adult care transition: a
      mixed-methods study in type 1 diabetes.
AB  - OBJECTIVE: Among the many milestones of adolescence and young adulthood,
      transferring from pediatric to adult care is a significant transition for those
      with type 1 diabetes. The aim of this study was to understand the concerns,
      expectations, preferences, and experiences of pretransition adolescents and
      parents and posttransition young adults. RESEARCH DESIGN AND METHODS:
      Participants completed questionnaires and responded to open-ended qualitative
      questions regarding self-management, self-efficacy, and their expectations and
      experiences with pediatric and adult care providers across the transition
      process. RESULTS: At a mean age of 16.1 years, most pretransition adolescents had
      not yet discussed transferring care with their parents or doctors. Although many
      posttransition young adults reported positive, supportive interactions, several
      described challenges locating or establishing a relationship with an adult
      diabetes care provider. Qualitative themes emerged related to the anticipated
      timing of transfer, early preparation for transition, the desire for
      developmentally appropriate interactions with providers, the maintenance of
      family and social support, and strategies for coordinating care between pediatric
      and adult care providers. CONCLUSIONS: Standardizing transition preparation
      programs in pediatric care and introducing transition-oriented clinics for late
      adolescents and young adults prior to adult care may help address patients'
      preferences and common transfer-related challenges.

PMID- 24089545
TI  - Association between excessive daytime sleepiness and severe hypoglycemia in
      people with type 2 diabetes: the Edinburgh Type 2 Diabetes Study.
AB  - OBJECTIVE: Sleep-disordered breathing and sleepiness cause metabolic, cognitive,
      and behavioral disturbance. Sleep-disordered breathing is common in type 2
      diabetes, a condition that requires adherence to complex dietary, behavioral, and
      drug treatment regimens. Hypoglycemia is an important side effect of treatment,
      causing physical and psychological harm and limiting ability to achieve optimal
      glycemic control. We hypothesized that sleep disorder might increase the risk of
      hypoglycemia through effects on self-management and glucose regulation. RESEARCH
      DESIGN AND METHODS: People with type 2 diabetes (n = 898) completed
      questionnaires to assess sleep-disordered breathing, daytime sleepiness, and
      occurrence of severe hypoglycemia. RESULTS: Subjects who scored highly on the
      Epworth Sleepiness Scale were significantly more likely to have suffered from
      severe hypoglycemia. This was a significant predictor of severe hypoglycemia in
      regression analysis including the variables age, sex, duration of diabetes,
      HbA1c, BMI, and treatment type. CONCLUSIONS: Daytime sleepiness may be a novel
      risk factor for hypoglycemia.

PMID- 24089546
TI  - Hyperglycemia and mortality among patients with coronary artery disease.
AB  - OBJECTIVE: Known diabetes is an independent predictor for mortality in coronary
      artery disease (CAD) patients; however, whether other glucose abnormalities are
      associated with death risk in CAD patients is unclear. The goal of this study was
      to examine the association between different glucose states and the risks of all
      cause and cardiovascular disease (CVD) mortality among CAD patients. RESEARCH
      DESIGN AND METHODS: The study cohort included 1,726 CAD patients who were 40-85
      years of age in the Guangdong Coronary Artery Disease Cohort. Cox proportional
      hazards regression models were used to estimate the association of baseline
      glucose status with risk of mortality. RESULTS: During a median follow-up of 3.1
      years, 129 deaths were recorded, 109 of which were due to CVD. The multivariable
      adjusted (age; sex; education; marriage; leisure-time physical activity; smoking;
      alcohol drinking; BMI; systolic blood pressure; total and HDL cholesterol;
      glomerular filtration rate; type, severity, duration, and treatment of CAD;
      history of heart failure; and use of antihypertensive, cholesterol-lowering, and
      antiplatelet drugs) hazard ratios in normoglycemia, impaired glucose regulation
      (IGR), newly diagnosed diabetes, and known diabetes were 1.00, 1.58 (95% CI 0.90
      2.77), 2.41 (1.42-4.11), and 2.29 (1.36-3.84) for all-cause mortality and 1.00,
      1.89 (1.01-3.54), 2.74 (1.50-5.01), and 2.73 (1.52-4.91) for CVD mortality.
      Assessing fasting plasma glucose only, impaired fasting glucose and newly
      diagnosed and known diabetes were also associated with increased risks of all
      cause and CVD mortality compared with normoglycemia. CONCLUSIONS: CAD patients
      with IGR, newly diagnosed diabetes, and known diabetes have increased risk of CVD
      mortality.

PMID- 24089547
TI  - Higher magnesium intake reduces risk of impaired glucose and insulin metabolism
      and progression from prediabetes to diabetes in middle-aged americans.
AB  - OBJECTIVE: To assess 7-year associations between magnesium intake and incident
      prediabetes and/or insulin resistance (IR), and progression from these states to
      type 2 diabetes. RESEARCH DESIGN AND METHODS: In 2,582 community-dwelling
      participants 26-81 years old at baseline, magnesium intake and risk of incident
      "metabolic impairment," defined as impaired fasting glucose (FG) (>=5.6 to <7.0
      mmol/L), impaired glucose tolerance (2-h postload glucose >=7.8 to <11.1 mmol/L),
      IR, or hyperinsulinemia (>=90th percentile of homeostasis model assessment of IR
      or fasting insulin, respectively), was estimated among those with normal baseline
      status, and risk of incident diabetes was estimated among those with baseline
      metabolic impairment. In participants without incident diabetes, we examined
      magnesium intake in relation to 7-year changes in fasting and postload glucose
      and insulin, IR, and insulin sensitivity. RESULTS: After adjusting for age, sex,
      and energy intake, compared with those with the lowest magnesium intake, those
      with the highest intake had 37% lower risk of incident metabolic impairment (P
      trend = 0.02), and in those with baseline metabolic impairment, higher intake was
      associated with 32% lower risk of incident diabetes (P trend = 0.05). In the
      combined population, the risk in those with the highest intake was 53% (P trend =
      0.0004) of those with the lowest intake. Adjusting for risk factors and dietary
      fiber attenuated associations in the baseline normal population but did not
      substantially affect associations in the metabolically impaired. Higher magnesium
      intake tended to associate with lower follow-up FG and IR, but not fasting
      insulin, postload values, or insulin sensitivity. CONCLUSIONS: Magnesium intake
      may be particularly beneficial in offsetting risk of developing diabetes among
      those at high risk. Magnesium's long-term associations with non-steady-state
      (dynamic) measures deserve further research.

PMID- 24089548
TI  - LINE-1 retrotransposable element DNA accumulates in HIV-1-infected cells.
AB  - Type 1 long-interspersed nuclear elements (L1s) are autonomous retrotransposable
      elements that retain the potential for activity in the human genome but are
      suppressed by host factors. Retrotransposition of L1s into chromosomal DNA can
      lead to genomic instability, whereas reverse transcription of L1 in the cytosol
      has the potential to activate innate immune sensors. We hypothesized that HIV-1
      infection would compromise cellular control of L1 elements, resulting in the
      induction of retrotransposition events. Here, we show that HIV-1 infection
      enhances L1 retrotransposition in Jurkat cells in a Vif- and Vpr-dependent
      manner. In primary CD4(+) cells, HIV-1 infection results in the accumulation of
      L1 DNA, at least the majority of which is extrachromosomal. These data expose an
      unrecognized interaction between HIV-1 and endogenous retrotransposable elements,
      which may have implications for the innate immune response to HIV-1 infection, as
      well as for HIV-1-induced genomic instability and cytopathicity. 

PMID- 24089549
TI  - Two overlapping regions within the N-terminal half of the herpes simplex virus 1
      E3 ubiquitin ligase ICP0 facilitate the degradation and dissociation of PML and
      dissociation of Sp100 from ND10.
AB  - Herpes simplex virus 1 (HSV-1) establishes a lifelong latent infection in sensory
      neurons and can reactivate from latency under stress conditions. To promote lytic
      infection, the virus must interact with specific cellular factors to evade the
      host's antiviral defenses. The HSV-1 E3 ubiquitin ligase, infected cell protein 0
      (ICP0), activates transcription of viral genes, in part, by mediating the
      degradation of certain cellular proteins that play a role in host antiviral
      mechanisms. One component of the cellular defenses that ICP0 disrupts is the
      suborganelle, nuclear domain 10 (ND10), by inducing the degradation and
      dissociation of the major organizer of ND10, a promyelocytic leukemia (PML) and
      ND10 constituent, Sp100. Because previously identified domains in ICP0 explain
      only partially how it directs the degradation and dissociation of PML and Sp100,
      we hypothesized that additional regions within ICP0 may contribute to these
      activities, which in turn facilitate efficient viral replication. To test this
      hypothesis, we used a series of ICP0 truncation mutants and examined PML protein
      levels and PML and Sp100 immunofluorescence staining in human embryonic lung
      cells. Our results demonstrate that two overlapping regions within the central N
      terminal portion of ICP0 (residues 212 to 311) promoted the dissociation and
      degradation of PML and dissociation of Sp100 (residues 212 to 427). In
      conclusion, we have identified two additional regions in ICP0 involved in
      altering ND10 antiviral defenses in a cell culture model of HSV-1 infection. 

PMID- 24089550
TI  - Rescue of maturation off-pathway products in the assembly of Pseudomonas phage
      phi 6.
AB  - Many complex viruses use an assembly pathway in which their genome is packaged
      into an empty procapsid which subsequently matures into its final expanded form.
      We utilized Pseudomonas phage 6, a well-established virus assembly model, to
      probe the plasticity of the procapsid maturation pathway. The 6 packaging
      nucleoside triphosphatase (NTPase), which powers sequential translocation of the
      three viral genomic single-stranded RNA molecules to the procapsid during capsid
      maturation, is part of the mature 6 virion but may spontaneously be dissociated
      from the procapsid shell. We demonstrate that the dissociation of NTPase subunits
      results in premature capsid expansion, which is detected as a change in the
      sedimentation velocity and as defects in RNA packaging and transcription
      activity. However, this dead-end conformation of the procapsids was rescued by
      the addition of purified NTPase hexamers, which efficiently associated on the
      NTPase-deficient particles and subsequently drove their contraction to the
      compact naive conformation. The resulting particles regained their biological and
      enzymatic activities, directing them into a productive maturation pathway. These
      observations imply that the maturation pathways of complex viruses may contain
      reversible steps that allow the rescue of the off-pathway conformation in an
      overall unidirectional virion assembly pathway. Furthermore, we provide direct
      experimental evidence that particles which have different physical properties
      (distinct sedimentation velocities and conformations) display different stages of
      the genome packaging program and show that the transcriptional activity of the 6
      procapsids correlates with the number of associated NTPase subunits. 

PMID- 24089551
TI  - The DNA virus white spot syndrome virus uses an internal ribosome entry site for
      translation of the highly expressed nonstructural protein ICP35.
AB  - Although shrimp white spot syndrome virus (WSSV) is a large double-stranded DNA
      virus (~300 kbp), it expresses many polycistronic mRNAs that are likely to use
      internal ribosome entry site (IRES) elements for translation. A polycistronic
      mRNA encodes the gene of the highly expressed nonstructural protein ICP35, and
      here we use a dual-luciferase assay to demonstrate that this protein is
      translated cap independently by an IRES element located in the 5' untranslated
      region of icp35. A deletion analysis of this region showed that IRES activity was
      due to stem-loops VII and VIII. A promoterless assay, a reverse transcription-PCR
      together with quantitative real-time PCR analysis, and a stable stem-loop
      insertion upstream of the Renilla luciferase open reading frame were used,
      respectively, to rule out the possibility that cryptic promoter activity,
      abnormal splicing, or read-through was contributing to the IRES activity. In
      addition, a Northern blot analysis was used to confirm that only a single
      bicistronic mRNA was expressed. The importance of ICP35 to viral replication was
      demonstrated in a double-stranded RNA (dsRNA) interference knockdown experiment
      in which the mortality of the icp35 dsRNA group was significantly reduced.
      Tunicamycin was used to show that the alpha subunit of eukaryotic initiation
      factor 2 is required for icp35 IRES activity. We also found that the
      intercalating drug quinacrine significantly inhibited icp35 IRES activity in
      vitro and reduced the mortality rate and viral copy number in WSSV-challenged
      shrimp. Lastly, in Sf9 insect cells, we found that knockdown of the gene for the
      Spodoptera frugiperda 40S ribosomal protein RPS10 decreased icp35 IRES-regulated
      firefly luciferase activity but had no effect on cap-dependent translation.

PMID- 24089552
TI  - Highly sensitive real-time in vivo imaging of an influenza reporter virus reveals
      dynamics of replication and spread.
AB  - The continual public health threat posed by the emergence of novel influenza
      viruses necessitates the ability to rapidly monitor infection and spread in
      experimental systems. To analyze real-time infection dynamics, we have created a
      replication-competent influenza reporter virus suitable for in vivo imaging. The
      reporter virus encodes the small and bright NanoLuc luciferase whose activity
      serves as an extremely sensitive readout of viral infection. This virus stably
      maintains the reporter construct and replicates in culture and in mice with near
      native properties. Bioluminescent imaging of the reporter virus permits serial
      observations of viral load and dissemination in infected animals, even following
      clearance of a sublethal challenge. We further show that the reporter virus
      recapitulates known restrictions due to host range and antiviral treatment,
      suggesting that this technology can be applied to studying emerging influenza
      viruses and the impact of antiviral interventions on infections in vivo. These
      results describe a generalizable method to quickly determine the replication and
      pathogenicity potential of diverse influenza strains in animals. 

PMID- 24089553
TI  - Cyclophilin A binds to the viral RNA and replication proteins, resulting in
      inhibition of tombusviral replicase assembly.
AB  - Replication of plus-stranded RNA viruses is greatly affected by numerous host
      encoded proteins that act as restriction factors. Cyclophilins, which are a large
      family of cellular prolyl isomerases, have been found to inhibit Tomato bushy
      stunt tombusvirus (TBSV) replication in a Saccharomyces cerevisiae model based on
      genome-wide screens and global proteomics approaches. In this report, we further
      characterize single-domain cyclophilins, including the mammalian cyclophilin A
      and plant Roc1 and Roc2, which are orthologs of the yeast Cpr1p cyclophilin, a
      known inhibitor of TBSV replication in yeast. We found that recombinant CypA,
      Roc1, and Roc2 strongly inhibited TBSV replication in a cell-free replication
      assay. Additional in vitro studies revealed that CypA, Roc1, and Roc2
      cyclophilins bound to the viral replication proteins, and CypA and Roc1 also
      bound to the viral RNA. These interactions led to inhibition of viral RNA
      recruitment, the assembly of the viral replicase complex, and viral RNA
      synthesis. A catalytically inactive mutant of CypA was also able to inhibit TBSV
      replication in vitro due to binding to the replication proteins and the viral
      RNA. Overexpression of CypA and its mutant in yeast or plant leaves led to
      inhibition of tombusvirus replication, confirming that CypA is a restriction
      factor for TBSV. Overall, the current work has revealed a regulatory role for the
      cytosolic single-domain Cpr1-like cyclophilins in RNA virus replication. 

PMID- 24089554
TI  - First insights into the entry process of hyperthermophilic archaeal viruses.
AB  - A decisive step in a virus infection cycle is the recognition of a specific
      receptor present on the host cell surface, subsequently leading to the delivery
      of the viral genome into the cell interior. Until now, the early stages of
      infection have not been thoroughly investigated for any virus infecting
      hyperthermophilic archaea. Here, we present the first study focusing on the
      primary interactions between the archaeal rod-shaped virus Sulfolobus islandicus
      rod-shaped virus 2 (SIRV2) (family Rudiviridae) and its hyperthermoacidophilic
      host, S. islandicus. We show that SIRV2 adsorption is very rapid, with the
      majority of virions being irreversibly bound to the host cell within 1 min. We
      utilized transmission electron microscopy and whole-cell electron cryotomography
      to demonstrate that SIRV2 virions specifically recognize the tips of pilus-like
      filaments, which are highly abundant on the host cell surface. Following the
      initial binding, the viral particles are found attached to the sides of the
      filaments, suggesting a movement along these appendages toward the cell surface.
      Finally, we also show that SIRV2 establishes superinfection exclusion, a
      phenomenon not previously described for archaeal viruses. 

PMID- 24089555
TI  - The viral ubiquitin ligase ICP0 is neither sufficient nor necessary for
      degradation of the cellular DNA sensor IFI16 during herpes simplex virus 1
      infection.
AB  - The cellular protein IFI16 colocalizes with the herpes simplex virus 1 (HSV-1)
      ubiquitin ligase ICP0 at early times of infection and is degraded as infection
      progresses. Here, we report that the factors governing the degradation of IFI16
      and its colocalization with ICP0 are distinct from those of promyelocytic
      leukemia protein (PML), a well-characterized ICP0 substrate. Unlike PML, IFI16
      colocalization with ICP0 was dependent on the ICP0 RING finger and did not occur
      when proteasome activity was inhibited. Expression of ICP0 in the absence of
      infection did not destabilize IFI16, the degradation occurred efficiently in the
      absence of ICP0 if infection was progressing efficiently, and IFI16 was
      relatively stable in wild-type (wt) HSV-1-infected U2OS cells. Therefore, IFI16
      stability appears to be regulated by cellular factors in response to active HSV-1
      infection rather than directly by ICP0. Because IFI16 is a DNA sensor that
      becomes associated with viral genomes during the early stages of infection, we
      investigated its role in the recruitment of PML nuclear body (PML NB) components
      to viral genomes. Recruitment of PML and hDaxx was less efficient in a proportion
      of IFI16-depleted cells, and this correlated with improved replication efficiency
      of ICP0-null mutant HSV-1. Because the absence of interferon regulatory factor 3
      (IRF3) does not increase the plaque formation efficiency of ICP0-null mutant HSV
      1, we speculate that IFI16 contributes to cell-mediated restriction of HSV-1 in a
      manner that is separable from its roles in IRF3-mediated interferon induction,
      but that may be linked to the PML NB response to viral infection. 

PMID- 24089556
TI  - Therapeutic vaccination against the rhesus lymphocryptovirus EBNA-1 homologue,
      rhEBNA-1, elicits T cell responses to novel epitopes in rhesus macaques.
AB  - Epstein-Barr virus (EBV) is a vaccine/immunotherapy target due to its association
      with several human malignancies. EBNA-1 is an EBV protein consistently expressed
      in all EBV-associated cancers. Herein, EBNA-1-specific T cell epitopes were
      evaluated after AdC-rhEBNA-1 immunizations in chronically lymphocryptovirus
      infected rhesus macaques, an EBV infection model. Preexisting rhEBNA-1-specific
      responses were augmented in 4/12 animals, and new epitopes were recognized in
      5/12 animals after vaccinations. This study demonstrated that EBNA-1-specific T
      cells can be expanded by vaccination. 

PMID- 24089557
TI  - Evasion of superinfection exclusion and elimination of primary viral RNA by an
      adapted strain of hepatitis C virus.
AB  - Cells that are productively infected by hepatitis C virus (HCV) are refractory to
      a second infection by HCV via a block in viral replication known as
      superinfection exclusion. The block occurs at a postentry step and likely
      involves translation or replication of the secondary viral RNA, but the mechanism
      is largely unknown. To characterize HCV superinfection exclusion, we selected for
      an HCV variant that could overcome the block. We produced a high-titer HC-J6/JFH1
      (Jc1) viral genome with a fluorescent reporter inserted between NS5A and NS5B and
      used it to infect Huh7.5 cells containing a Jc1 replicon. With multiple passages
      of these infected cells, we isolated an HCV variant that can superinfect cells at
      high levels. Notably, the superinfectious virus rapidly cleared the primary
      replicon from superinfected cells. Viral competition experiments, using a novel
      strategy of sequence-barcoding viral strains, as well as superinfection of
      replicon cells demonstrated that mutations in E1, p7, NS5A, and the poly(U/UC)
      tract of the 3' untranslated region were important for superinfection.
      Furthermore, these mutations dramatically increased the infectivity of the virus
      in naive cells. Interestingly, viruses with a shorter poly(U/UC) and an NS5A
      domain II mutation were most effective in overcoming the postentry block. Neither
      of these changes affected viral RNA translation, indicating that the major
      barrier to postentry exclusion occurs at viral RNA replication. The evolution of
      the ability to superinfect after less than a month in culture and the concomitant
      exclusion of the primary replicon suggest that superinfection exclusion
      dramatically affects viral fitness and dynamics in vivo. 

PMID- 24089558
TI  - Hepatitis B virus inhibits apoptosis of hepatoma cells by sponging the MicroRNA
      15a/16 cluster.
AB  - Hepatitis B virus (HBV) causes chronic hepatitis in hundreds of millions of
      people worldwide, which can eventually lead to hepatocellular carcinoma (HCC).
      The molecular mechanisms underlying HBV persistence are not well understood. In
      this study, we found that HBV inhibited the chemotherapy drug etoposide-induced
      apoptosis of hepatoma cells. Further analysis revealed that HBV mRNAs possess a
      microRNA 15a/16 (miR-15a/16)-complementary site (HBV nucleotides [nt] 1362 to
      1383) that acts as a sponge to bind and sequester endogenous miR-15a/16.
      Consequently, Bcl-2, known as the target of miR-15a/16, was upregulated in HBV
      infected cells. The data from HBV-transgenic mice further confirmed that HBV
      transcripts cause the reduction of miR-15a/16 and increase of Bcl-2. More
      importantly, we examined the levels of HBV transcripts and miR-15a/16 in HBV
      infected HCC from patients and found that the amount of HBV mRNA and the level of
      miR-15a/16 were negatively correlated. Consistently, the level of Bcl-2 mRNA was
      upregulated in HBV-infected patients. In conclusion, we identified a novel HBV
      mRNA-miR-15a/16-Bcl-2 regulatory pathway that is involved in inhibiting etoposide
      induced apoptosis of hepatoma cells, which may contribute to facilitating chronic
      HBV infection and hepatoma development. 

PMID- 24089559
TI  - Absence of CD14 delays progression of prion diseases accompanied by increased
      microglial activation.
AB  - Prion diseases are fatal neurodegenerative disorders characterized by
      accumulation of PrP(Sc), vacuolation of neurons and neuropil, astrocytosis, and
      microglial activation. Upregulation of gene expressions of innate immunity
      related factors, including complement factors and CD14, is observed in the brains
      of mice infected with prions even in the early stage of infections. When CD14
      knockout (CD14(-/-)) mice were infected intracerebrally with the Chandler and
      Obihiro prion strains, the mice survived longer than wild-type (WT) mice,
      suggesting that CD14 influences the progression of the prion disease.
      Immunofluorescence staining that can distinguish normal prion protein from the
      disease-specific form of prion protein (PrP(Sc)) revealed that deposition of
      PrP(Sc) was delayed in CD14(-/-) mice compared with WT mice by the middle stage
      of the infection. Immunohistochemical staining with Iba1, a marker for activated
      microglia, showed an increased microglial activation in prion-infected CD14(-/-)
      mice compared to WT mice. Interestingly, accompanied by the increased microglial
      activation, anti-inflammatory cytokines interleukin-10 (IL-10) and transforming
      growth factor beta (TGF-beta) appeared to be expressed earlier in prion-infected
      CD14(-/-) mice. In contrast, IL-1beta expression appeared to be reduced in the
      CD14(-/-) mice in the early stage of infection. Double immunofluorescence
      staining demonstrated that CD11b- and Iba1-positive microglia mainly produced the
      anti-inflammatory cytokines, suggesting anti-inflammatory status of microglia in
      the CD14(-/-) mice in the early stage of infection. These results imply that CD14
      plays a role in the disease progression by suppressing anti-inflammatory
      responses in the brain in the early stage of infection. 

PMID- 24089560
TI  - Alpha interferon restricts human T-lymphotropic virus type 1 and 2 de novo
      infection through PKR activation.
AB  - Type I interferon (IFN-I) inhibits the replication of different viruses. However,
      the effect of IFN-I on the human T-lymphotropic virus type 1 (HTLV-1) viral cycle
      is controversial. Here, we investigated the consequences of IFN-alpha addition
      for different steps of HTLV-1 and HTLV-2 infection. We first show that alpha
      interferon (IFN-alpha) efficiently impairs HTLV-1 and HTLV-2 de novo infection in
      a T cell line and in primary lymphocytes. Using pseudotyped viruses expressing
      HTLV-1 envelope, we then show that cell-free infection is insensitive to IFN
      alpha, demonstrating that the cytokine does not affect the early stages of the
      viral cycle. In contrast, intracellular levels of Gag, Env, or Tax protein are
      affected by IFN-alpha treatment in T cells, primary lymphocytes, or 293T cells
      transfected with HTLV-1 or HTLV-2 molecular clones, demonstrating that IFN-alpha
      acts during the late stages of infection. We show that IFN-alpha does not affect
      Tax-mediated transcription and acts at a posttranscriptional level. Using either
      small interfering RNA (siRNA) directed against PKR or a PKR inhibitor, we
      demonstrate that PKR, whose expression is induced by interferon, plays a major
      role in IFN-alpha-induced HTLV-1/2 inhibition. These results indicate that IFN
      alpha has a strong repressive effect on the HTLV-1 and HTLV-2 viral cycle during
      de novo infection of cells that are natural targets of the viruses. 

PMID- 24089561
TI  - Respiratory syncytial virus G protein CX3C motif impairs human airway epithelial
      and immune cell responses.
AB  - Respiratory syncytial virus (RSV) is a major cause of severe lower respiratory
      infection in infants and young children and causes disease in the elderly and
      persons with compromised cardiac, pulmonary, or immune systems. Despite the high
      morbidity rates of RSV infection, no highly effective treatment or vaccine is yet
      available. The RSV G protein is an important contributor to the disease process.
      A conserved CX3C chemokine-like motif in G likely contributes to the pathogenesis
      of disease. Through this motif, G protein binds to CX3CR1 present on various
      immune cells and affects immune responses to RSV, as has been shown in the mouse
      model of RSV infection. However, very little is known of the role of RSV CX3C
      CX3CR1 interactions in human disease. In this study, we use an in vitro model of
      human RSV infection comprised of human peripheral blood mononuclear cells (PBMCs)
      separated by a permeable membrane from human airway epithelial cells (A549)
      infected with RSV with either an intact CX3C motif (CX3C) or a mutated motif
      (CX4C). We show that the CX4C virus induces higher levels of type I/III
      interferon (IFN) in A549 cells, increased IFN-alpha and tumor necrosis factor
      alpha (TNF-alpha) production by human plasmacytoid dendritic cells (pDCs) and
      monocytes, and increased IFN-gamma production in effector/memory T cell
      subpopulations. Treatment of CX3C virus-infected cells with the F(ab')2 form of
      an anti-G monoclonal antibody (MAb) that blocks binding to CX3CR1 gave results
      similar to those with the CX4C virus. Our data suggest that the RSV G protein
      CX3C motif impairs innate and adaptive human immune responses and may be
      important to vaccine and antiviral drug development. 

PMID- 24089562
TI  - Characterization of hepatitis C virus intra- and intergenotypic chimeras reveals
      a role of the glycoproteins in virus envelopment.
AB  - Hepatitis C virus (HCV) is highly variable and associated with chronic liver
      disease. Viral isolates are grouped into seven genotypes (GTs). Accumulating
      evidence indicates that viral determinants in the core to NS2 proteins modulate
      the efficiency of virus production. However, the role of the glycoproteins E1 and
      E2 in this process is currently poorly defined. Therefore, we constructed
      chimeric viral genomes to explore the role of E1 and E2 in HCV assembly.
      Comparison of the kinetics and efficiency of particle production by
      intragenotypic chimeras highlighted core and p7 as crucial determinants for
      efficient virion release. Glycoprotein sequences, however, had only a minimal
      impact on this process. In contrast, in the context of intergenotypic HCV
      chimeras, HCV assembly was profoundly influenced by glycoprotein genes. On the
      one hand, insertion of GT1a-derived (H77) E1-E2 sequences into a chimeric GT2a
      virus (Jc1) strongly suppressed virus production. On the other hand, replacement
      of H77 glycoproteins within the GT1a-GT2a chimeric genome H77/C3 by GT2a-derived
      (Jc1) E1-E2 increased infectious particle production. Thus, within intergenotypic
      chimeras, glycoprotein features strongly modulate virus production. Replacement
      of Jc1 glycoprotein genes by H77-derived E1-E2 did not grossly affect subcellular
      localization of core, E2, and NS2. However, it caused an accumulation of
      nonenveloped core protein and increased abundance of nonenveloped core protein
      structures with slow sedimentation. These findings reveal an important role for
      the HCV glycoproteins E1 and E2 in membrane envelopment, which likely depends on
      a genotype-specific interplay with additional viral factors. 

PMID- 24089563
TI  - Spherical influenza viruses have a fitness advantage in embryonated eggs, while
      filament-producing strains are selected in vivo.
AB  - Influenza viruses can take on two distinct morphologies: filamentous or
      spherical. While the functional significance of each virion type is unclear,
      filaments are generally observed in low-passage-number isolates, while an
      exclusively spherical morphology is seen in strains grown extensively in
      laboratory substrates. Previous studies have shown that filamentous morphology is
      lost upon passage in eggs. The fact that the filamentous morphology is maintained
      in nature but not in the laboratory suggests that filaments provide an advantage
      in the host that is not necessary for growth in laboratory substrates. To test
      this hypothesis and identify naturally occurring mutations that alter morphology,
      we examined the effect of serial adaptation in eggs, MDCK cells, and guinea pigs.
      Two filamentous strains, A/Netherlands/602/2009 (H1N1) and A/Georgia/M5081/2012
      (H1N1), were passaged in eggs and MDCK cells. Conversely, the spherical
      laboratory strain A/Puerto Rico/8/1934 (H1N1) was passaged in guinea pigs. We
      found that although passage in eggs and MDCK cells can lead to a loss of
      filaments, an exclusively spherical morphology is not required for highly
      efficient growth in either substrate. We did, however, identify two point
      mutations in the matrix of egg passage 10 isolates that confer spherical
      morphology and increased growth in eggs. In contrast, serial passage in guinea
      pigs resulted in the selection of filament-forming variants. Sequencing revealed
      point mutations to the PR8 matrix that, when introduced individually, yielded
      filaments. These findings suggest a functional role for filaments in the infected
      host and expand the breadth of mutations known to affect influenza virus shape. 

PMID- 24089565
TI  - Epizootic hemorrhagic disease virus induces and benefits from cell stress,
      autophagy, and apoptosis.
AB  - The mode and timing of virally induced cell death hold the potential of
      regulating viral yield, viral transmission, and the severity of virally induced
      disease. Orbiviruses such as the epizootic hemorrhagic disease virus (EHDV) are
      nonenveloped and cytolytic. To date, the death of cells infected with EHDV, the
      signal transduction pathways involved in this process, and the consequence of
      their inhibition have yet to be characterized. Here, we report that the Ibaraki
      strain of EHDV2 (EHDV2-IBA) induces apoptosis, autophagy, a decrease in cellular
      protein synthesis, the activation of c-Jun N-terminal kinase (JNK), and the
      phosphorylation of the JNK substrate c-Jun. The production of infectious virions
      decreased upon inhibition of apoptosis with the pan-caspase inhibitor Q-VD-OPH
      (quinolyl-valyl-O-methylaspartyl-[-2,6-difluorophenoxy]-methyl ketone), upon
      inhibition of autophagy with 3-methyladenine or via the knockout of the autophagy
      regulator Atg5, or upon treatment of infected cells with the JNK inhibitor
      SP600125 or the cyclin-dependent kinase (CDK) inhibitor roscovitine, which also
      inhibited c-Jun phosphorylation. Moreover, Q-VD-OPH, SP600125, and roscovitine
      partially reduced EHDV2-IBA-induced cell death, and roscovitine diminished the
      induction of autophagy by EHDV2-IBA. Taken together, our results imply that EHDV
      induces and benefits from the activation of signaling pathways involved in cell
      stress and death. 

PMID- 24089564
TI  - Cytoplasmic granule formation and translational inhibition of nodaviral RNAs in
      the absence of the double-stranded RNA binding protein B2.
AB  - Flock House virus (FHV) is a positive-sense RNA insect virus with a bipartite
      genome. RNA1 encodes the RNA-dependent RNA polymerase, and RNA2 encodes the
      capsid protein. A third protein, B2, is translated from a subgenomic RNA3 derived
      from the 3' end of RNA1. B2 is a double-stranded RNA (dsRNA) binding protein that
      inhibits RNA silencing, a major antiviral defense pathway in insects. FHV is
      conveniently propagated in Drosophila melanogaster cells but can also be grown in
      mammalian cells. It was previously reported that B2 is dispensable for FHV RNA
      replication in BHK21 cells; therefore, we chose this cell line to generate a
      viral mutant that lacked the ability to produce B2. Consistent with published
      results, we found that RNA replication was indeed vigorous but the yield of
      progeny virus was negligible. Closer inspection revealed that infected cells
      contained very small amounts of coat protein despite an abundance of RNA2. B2
      mutants that had reduced affinity for dsRNA produced analogous results,
      suggesting that the dsRNA binding capacity of B2 somehow played a role in coat
      protein synthesis. Using fluorescence in situ hybridization of FHV RNAs, we
      discovered that RNA2 is recruited into large cytoplasmic granules in the absence
      of B2, whereas the distribution of RNA1 remains largely unaffected. We conclude
      that B2, by binding to double-stranded regions in progeny RNA2, prevents
      recruitment of RNA2 into cellular structures, where it is translationally
      silenced. This represents a novel function of B2 that further contributes to
      successful completion of the nodaviral life cycle. 

PMID- 24089566
TI  - Highly divergent strains of porcine reproductive and respiratory syndrome virus
      incorporate multiple isoforms of nonstructural protein 2 into virions.
AB  - Viral structural proteins form the critical intermediary between viral infection
      cycles within and between hosts, function to initiate entry, participate in
      immediate early viral replication steps, and are major targets for the host
      adaptive immune response. We report the identification of nonstructural protein 2
      (nsp2) as a novel structural component of the porcine reproductive and
      respiratory syndrome virus (PRRSV) particle. A set of custom alpha-nsp2
      antibodies targeting conserved epitopes within four distinct regions of nsp2 (the
      PLP2 protease domain [OTU], the hypervariable domain [HV], the putative
      transmembrane domain [TM], and the C-terminal region [C]) were obtained
      commercially and validated in PRRSV-infected cells. Highly purified cell-free
      virions of several PRRSV strains were isolated through multiple rounds of
      differential density gradient centrifugation and analyzed by immunoelectron
      microscopy (IEM) and Western blot assays using the alpha-nsp2 antibodies.
      Purified viral preparations were found to contain pleomorphic, predominantly
      spherical virions of uniform size (57.9 nm +/- 8.1 nm diameter; n = 50),
      consistent with the expected size of PRRSV particles. Analysis by IEM indicated
      the presence of nsp2 associated with the viral particle of diverse strains of
      PRRSV. Western blot analysis confirmed the presence of nsp2 in purified viral
      samples and revealed that multiple nsp2 isoforms were associated with the virion.
      Finally, a recombinant PRRSV genome containing a myc-tagged nsp2 was used to
      generate purified virus, and these particles were also shown to harbor myc-tagged
      nsp2 isoforms. Together, these data identify nsp2 as a virion-associated
      structural PRRSV protein and reveal that nsp2 exists in or on viral particles as
      multiple isoforms. 

PMID- 24089567
TI  - Epstein-Barr virus coinfection in children boosts cytomegalovirus-induced
      differentiation of natural killer cells.
AB  - During childhood, infections with cytomegalovirus (CMV) and Epstein-Barr virus
      (EBV) can occur in close temporal proximity. Active, as well as latent, CMV
      infection is associated with enlarged subsets of differentiated natural killer
      (NK) and cytotoxic T cells. How EBV infection may influence CMV-driven immune
      differentiation is not known. We found that EBV coinfection selectively
      influenced the NK cell compartment of CMV-seropositive (CMV(+)) children.
      Coinfected children had significantly higher proportions of peripheral-blood
      NKG2C(+) NK cells than CMV(+) EBV(-) children. Ex vivo NK cell degranulation
      after target cell stimulation and plasma IL-15 levels were significantly higher
      in CMV(+) children. EBV coinfection was related to the highest levels of plasma
      interleukin-15 (IL-15) and IL-12p70. Remarkably, in vitro EBV infection of
      peripheral blood mononuclear cells (PBMC) from EBV(-) CMV(+) children increased
      NKG2C(+) NK cell proportions. A similar tendency was seen in cocultures of PBMC
      with EBV(+) lymphoblastoid B-cell lines (LCL) and IL-15. After K562 challenge,
      NKG2C(+) NK cells excelled in regard to degranulation and production of gamma
      interferon, regardless of whether there was previous coculture with LCL. Taken
      together, our data suggest that dual latency with these herpesviruses during
      childhood could contribute to an in vivo environment supporting differentiation
      and maintenance of distinct NK cell populations. This viral imprint may affect
      subsequent immune responses through altered distributions of effector cells. 

PMID- 24089568
TI  - 5-HT2 receptors facilitate JC polyomavirus entry.
AB  - The human JC polyomavirus (JCPyV) causes the rapidly progressing demyelinating
      disease progressive multifocal leukoencephalopathy (PML). The disease occurs most
      often in individuals with AIDS but also occurs in individuals receiving
      immunomodulatory therapies for immune-related diseases such as multiple
      sclerosis. JCPyV infection of host cells requires the pentasaccharide lactoseries
      tetrasaccharide c (LSTc) and the serotonin receptor 5-hydroxytryptamine (5-HT)
      receptor 5-HT2AR. While LSTc is involved in the initial attachment of virus to
      cells via interactions with VP1, the mechanism by which 5-HT2AR contributes to
      infection is not clear. To further define the roles of serotonin receptors in
      infection, HEK293A cells, which are poorly permissive to JCPyV, were transfected
      with 14 different isoforms of serotonin receptor. Only 5-HT2 receptors were found
      to support infection by JCPyV. None of the other 11 isoforms of serotonin
      receptor supported JCPyV infection. Expression of 5-HT2 receptors did not
      increase binding of JCPyV to cells, but this was not unexpected, given that the
      cells uniformly expressed the major attachment receptor, LSTc. Infection of these
      cells remained sensitive to inhibition with soluble LSTc, confirming that LSTc
      recognition is required for JCPyV infection. Virus internalization into HEK293A
      cells was significantly and specifically enhanced when 5HT2 receptors were
      expressed. Taken together, these data confirm that the carbohydrate LSTc is the
      attachment receptor for JCPyV and that the type 2 serotonin receptors contribute
      to JCPyV infection by facilitating entry. 

PMID- 24089569
TI  - Impact of prior seasonal H3N2 influenza vaccination or infection on protection
      and transmission of emerging variants of influenza A(H3N2)v virus in ferrets.
AB  - Influenza H3N2 A viruses continue to circulate in swine and occasionally infect
      humans, resulting in outbreaks of variant influenza H3N2 [A(H3N2)v] virus. It has
      been previously demonstrated in ferrets that A(H3N2)v viruses transmit as
      efficiently as seasonal influenza viruses, raising concern over the pandemic
      potential of these viruses. However, A(H3N2)v viruses have not acquired the
      ability to transmit efficiently among humans, which may be due in part to
      existing cross-reactive immunity to A(H3N2)v viruses. Although current seasonal
      H3N2 and A(H3N2)v viruses are antigenically distinct from one another, historical
      H3N2 viruses have some antigenic similarity to A(H3N2)v viruses and previous
      exposure to these viruses may provide a measure of immune protection sufficient
      to dampen A(H3N2)v virus transmission. Here, we evaluated whether prior seasonal
      H3N2 influenza virus vaccination or infection affects virus replication and
      transmission of A(H3N2)v virus in the ferret animal model. We found that the
      seasonal trivalent inactivated influenza virus vaccine (TIV) or a monovalent
      vaccine prepared from an antigenically related 1992 seasonal influenza H3N2
      (A/Beijing/32/1992) virus failed to substantially reduce A(H3N2)v
      (A/Indiana/08/2011) virus shedding and subsequent transmission to naive hosts.
      Conversely, ferrets primed by seasonal H3N2 virus infection displayed reduced
      A(H3N2)v virus shedding following challenge, which blunted transmission to naive
      ferrets. A higher level of specific IgG and IgA antibody titers detected among
      infected versus vaccinated ferrets was associated with the degree of protection
      offered by seasonal H3N2 virus infection. The data demonstrate in ferrets that
      the efficiency of A(H3N2)v transmission is disrupted by preexisting immunity
      induced by seasonal H3N2 virus infection. 

PMID- 24089570
TI  - Two independent regions of simian virus 40 T antigen increase CBP/p300 levels,
      alter patterns of cellular histone acetylation, and immortalize primary cells.
AB  - Simian virus 40 (SV40) large T antigen (SVT) interferes with normal cell
      regulation and thus has been used to identify cellular components controlling
      proliferation and homeostasis. We have previously shown that SVT-mediated
      transformation requires interaction with the histone acetyltransferases (HATs)
      CBP/p300 and now report that the ectopic expression of SVT in several cell types
      in vivo and in vitro results in a significant increase in the steady-state levels
      of CBP/p300. Furthermore, SVT-expressing cells contain higher levels of
      acetylated CBP/p300, a modification that has been linked to increased HAT
      activity. Concomitantly, the acetylation levels of histone residues H3K56 and
      H4K12 are markedly increased in SVT-expressing cells. Other polyomavirus-encoded
      large T antigens also increase the levels of CBP/p300 and sustain a rise in the
      acetylation levels of H3K56 and H4K12. SVT does not affect the transcription of
      CBP/p300, but rather, alters their overall levels through increasing the loading
      of CBP/p300 mRNAs onto polysomes. Two distinct regions within SVT, one located in
      the amino terminus and one in the carboxy terminus, can independently alter both
      the levels of CBP/p300 and the loading of CBP/p300 transcripts onto polysomes.
      Within the amino-terminal fragment, a functional J domain is necessary for
      increasing CBP/p300 and specific histone acetylation levels, as well as for
      immortalizing primary cells. These studies uncover the action of polyomavirus T
      antigens on cellular CBP/p300 and suggest that additional mechanisms are used by
      T antigens to induce cell immortalization and transformation. 

PMID- 24089571
TI  - The ha72 core gene of baculovirus is essential for budded virus production and
      occlusion-derived virus embedding, and amino acid K22 plays an important role in
      its function.
AB  - ha72 of Helicoverpa armigera nucleopolyhedrovirus (a homologue of ac78) was
      identified as a conserved late baculovirus gene and characterized. HA72 localizes
      in the intranuclear ring zone. By generating mutants, we showed that HA72 is
      essential for budded virus (BD) production and occlusion-derived virus (ODV)
      embedding. HA72 also interacted with P33, a baculoviral sulfhydryl oxidase. A
      point mutation of amino acid 22 from lysine to glutamic acid curtailed BV
      production and precluded ODV occlusion as well as interaction with P33. 

PMID- 24089573
TI  - Characteristics of oncolytic vesicular stomatitis virus displaying tumor
      targeting ligands.
AB  - We sought proof of principle that tumor-targeting ligands can be displayed on the
      surface of vesicular stomatitis virus (VSV) by engineering its glycoprotein.
      Here, we successfully rescued VSVs displaying tumor vasculature-targeting
      ligands. By using a rational approach, we investigated various feasible insertion
      sites on the G protein of VSV (VSV-G) for display of tumor vasculature-targeting
      ligands, cyclic RGD (cRGD) and echistatin. We found seven sites on VSV-G that
      tolerated insertion of the 9-residue cRGD peptide, two of which could tolerate
      insertion of the 49-amino acid echistatin domain. All of the ligand-displaying
      viruses replicated as well as the parental virus. In vitro studies demonstrated
      that the VSV-echistatin viruses specifically bound to targeted integrins. Since
      the low-density lipoprotein receptor (LDLR) was recently identified as a major
      receptor for VSV, we investigated the entry of ligand-displaying viruses after
      masking LDLR. The experiment showed that the modified viruses can enter the cell
      independently of LDLR, whereas entry of unmodified virus is significantly blocked
      by a specific monoclonal antibody against LDLR. Both parental and ligand
      displaying viruses displayed equal oncolytic efficacies in a syngeneic mouse
      myeloma model. We further demonstrated that single-chain antibody fragments
      against tumor-specific antigens can be inserted at the N terminus of the G
      protein and that corresponding replication-competent VSVs can be rescued
      efficiently. Overall, we demonstrated that functional tumor-targeting ligands can
      be displayed on replication-competent VSVs without perturbing viral growth and
      oncolytic efficacy. This study provides a rational foundation for the future
      development of fully retargeted oncolytic VSVs. 

PMID- 24089572
TI  - Mutations in the parainfluenza virus 5 fusion protein reveal domains important
      for fusion triggering and metastability.
AB  - Paramyxovirus membrane glycoproteins F (fusion protein) and HN, H, or G
      (attachment protein) are critical for virus entry, which occurs through fusion of
      viral and cellular envelopes. The F protein folds into a homotrimeric, metastable
      prefusion form that can be triggered by the attachment protein to undergo a
      series of structural rearrangements, ultimately folding into a stable postfusion
      form. In paramyxovirus-infected cells, the F protein is activated in the Golgi
      apparatus by cleavage adjacent to a hydrophobic fusion peptide that inserts into
      the target membrane, eventually bringing the membranes together by F refolding.
      However, it is not clear how the attachment protein, known as HN in parainfluenza
      virus 5 (PIV5), interacts with F and triggers F to initiate fusion. To understand
      the roles of various F protein domains in fusion triggering and metastability,
      single point mutations were introduced into the PIV5 F protein. By extensive
      study of F protein cleavage activation, surface expression, and energetics of
      fusion triggering, we found a role for an immunoglobulin-like (Ig-like) domain,
      where multiple hydrophobic residues on the PIV5 F protein may mediate F-HN
      interactions. Additionally, destabilizing mutations of PIV5 F that resulted in HN
      trigger-independent mutant F proteins were identified in a region along the
      border of F trimer subunits. The positions of the potential HN-interacting region
      and the region important for F stability in the lower part of the PIV5 F
      prefusion structure provide clues to the receptor-binding initiated, HN-mediated
      F trigger. 

PMID- 24089574
TI  - Herpes simplex virus 1 ICP22 but not US 1.5 is required for efficient acute
      replication in mice and VICE domain formation.
AB  - The herpes simplex virus 1 (HSV-1) immediate-early protein, infected cell protein
      22 (ICP22), is required for efficient replication in restrictive cells, for virus
      induced chaperone-enriched (VICE) domain formation, and for normal expression of
      a subset of viral late proteins. Additionally, ICP22 is important for optimal
      acute viral replication in vivo. Previous studies have shown that the US1 gene
      that encodes ICP22, produces an in-frame, N-terminally truncated form of ICP22,
      known as US1.5. To date, studies conducted to characterize the functions of ICP22
      have not separated its functions from those of US1.5. To determine the individual
      roles of ICP22 and US1.5, we made viral mutants that express either ICP22 with an
      M90A mutation in the US1.5 initiation codon (M90A) or US1.5 with three stop
      codons introduced upstream of the US1.5 start codon (3*stop). Our studies showed
      that, in contrast to M90A, 3*stop was unable to replicate efficiently in the eyes
      and trigeminal ganglia of mice during acute infection, to efficiently establish a
      latent infection, or to induce VICE domain formation and was only mildly reduced
      in its replication in restrictive HEL-299 cells and murine embryonic fibroblasts
      (MEFs). Both mutants enhanced the expression of the late viral proteins virion
      host shutoff (vhs) and glycoprotein C (gC) and inhibited viral gene expression
      mediated by HSV-1 infected cell protein 0 (ICP0). When we tested our mutants'
      sensitivity to type I interferon (beta interferon [IFN-beta]) in restrictive
      cells, we noticed that the plating of the ICP22 null (d22) and 3*stop mutants was
      reduced by the addition of IFN-beta. Overall, our data suggest that US1.5
      partially complements the functions of ICP22. 

PMID- 24089575
TI  - The MU1 72-96 loop controls conformational transitions during reovirus cell
      entry.
AB  - The reovirus outer capsid protein MU1 forms a lattice surrounding the viral core.
      In the native state, MU1 determines the environmental stability of the viral
      capsid. Additionally, during cell entry, MU1 undergoes structural rearrangements
      that facilitate delivery of the viral cores across the membrane. To determine how
      the capsid-stabilizing functions of MU1 impinge on the capacity of MU1 to undergo
      conformational changes required for cell entry, we characterized viruses with
      mutations engineered at charged residues within the MU1 loop formed by residues
      72 to 96 (72-96 loop). This loop is proposed to stabilize the capsid by mediating
      interactions between neighboring MU1 trimers and between trimers and the core. We
      found that mutations at Glu89 (E89) within this loop produced viruses with
      compromised efficiency for completing their replication cycle. ISVPs of E89
      mutants converted to ISVP*s more readily than those of wild-type viruses. The E89
      mutants yielded revertants with second-site substitutions within regions that
      mediate interaction between MU1 trimers at a site distinct from the 72-96 loop.
      These viruses also contained changes in regions that control interactions within
      MU1 trimers. Viruses containing these second-site changes displayed restored
      plaque phenotypes and were capable of undergoing ISVP-to-ISVP* conversion in a
      regulated manner. These findings highlight regions of MU1 that stabilize the
      reovirus capsid and demonstrate that an enhanced propensity to form ISVP*s in an
      unregulated manner compromises viral fitness. 

PMID- 24089576
TI  - A cost-effective and simple alternative technique for reconstitution of freeze
      dried cultures of Neisseria gonorrhoeae.

PMID- 24089577
TI  - Resistance to ceftazidime in Escherichia coli associated with AcrR, MarR and PBP3
      mutations and overexpression of sdiA.
AB  - The mechanisms responsible for the increase in ceftazidime MIC in two Escherichia
      coli in vitro selected mutants, Caz/20-1 and Caz/20-2, were studied. OmpF loss
      and overexpression of acrB, acrD and acrF that were associated with acrR and marR
      mutations and sdiA overexpression, together with mutations A233T and I332V in
      FtSI (PBP3) resulted in ceftazidime resistance in Caz/20-2, multiplying by 128
      fold the ceftazidime MIC in the parental clinical isolate PS/20. Absence of
      detectable beta-lactamase hydrolytic activity in the crude extract of Caz/20-2
      was observed, and coincided with Q191K and P209S mutations in AmpC and a
      nucleotide substitution at -28 in the ampC promoter, whereas beta-lactamase
      hydrolytic activity in crude extracts of PS/20 and Caz/20-1 strains was detected.
      Nevertheless, a fourfold increase in ceftazidime MIC in Caz/20-1 compared with
      that in PS/20 was due to the increased transcript level of acrB derived from acrR
      mutation. The two Caz mutants and PS/20 showed the same mutations in AmpG and
      ParE.

PMID- 24089578
TI  - Role of porin proteins in acquisition of transferrin iron by enteropathogens.
AB  - Acquisition of iron from key innate immune defence proteins such as transferrin
      (Tf) and lactoferrin is an important mechanism by which pathogenic bacteria
      obtain essential iron for growth within their host. Bacterial species that do not
      produce siderophores often use specific Tf-binding proteins, the best
      characterized being the Neisseriaceae-type Tf-binding proteins TbpA and TbpB.
      Previous work from our laboratory has shown that siderophore-producing enteric
      species such as Escherichia coli also readily bind Tf, although no genomic
      evidence exists for Tbp-like Tf-binding proteins. Application of proteomic
      analyses and molecular mutagenesis strategies to an enteropathogenic E. coli
      identified the OmpA and OmpC porins as Tf-binding proteins. Mutagenesis of the
      ompA or ompC genes affected E. coli Tf binding and, furthermore, compromised the
      ability of the ompA mutant to respond to growth promotion by certain
      catecholamine stress hormones. Evidence was also found to implicate the OmpA
      porin as an entry point for catecholamine stress hormones. Further proteomic
      analyses in other bacterial pathogens revealed wide-scale involvement of porins
      in Tf binding: Salmonella typhimurium (OmpC), and Shigella sonnei, Shigella
      flexneri and Shigella boydii (OmpC and/or OmpA). This study shows that in
      addition to their existing housekeeping functions, the Gram-negative porin family
      of proteins can also act as Tf-capture proteins for those bacteria that lack the
      classical Neisseriaceae-type Tf-binding proteins. 

PMID- 24089579
TI  - Bayesian Approach for Inconsistent Information.
AB  - In engineering situations, we usually have a large amount of prior knowledge that
      needs to be taken into account when processing data. Traditionally, the Bayesian
      approach is used to process data in the presence of prior knowledge. Sometimes,
      when we apply the traditional Bayesian techniques to engineering data, we get
      inconsistencies between the data and prior knowledge. These inconsistencies are
      usually caused by the fact that in the traditional approach, we assume that we
      know the exact sample values, that the prior distribution is exactly known, etc.
      In reality, the data is imprecise due to measurement errors, the prior knowledge
      is only approximately known, etc. So, a natural way to deal with the seemingly
      inconsistent information is to take this imprecision into account in the Bayesian
      approach - e.g., by using fuzzy techniques. In this paper, we describe several
      possible scenarios for fuzzifying the Bayesian approach. Particular attention is
      paid to the interaction between the estimated imprecise parameters. In this
      paper, to implement the corresponding fuzzy versions of the Bayesian formulas, we
      use straightforward computations of the related expression - which makes our
      computations reasonably time-consuming. Computations in the traditional (non
      fuzzy) Bayesian approach are much faster - because they use algorithmically
      efficient reformulations of the Bayesian formulas. We expect that similar
      reformulations of the fuzzy Bayesian formulas will also drastically decrease the
      computation time and thus, enhance the practical use of the proposed methods.

PMID- 24089580
TI  - Structural investigation of GaInP nanowires using X-ray diffraction.
AB  - In this work the structure of ternary Ga x In1 - x P nanowires is investigated
      with respect to the chemical composition and homogeneity. The nanowires were
      grown by metal-organic vapor-phase epitaxy. For the investigation of ensemble
      fluctuations on several lateral length scales, X-ray diffraction reciprocal space
      maps have been analyzed. The data reveal a complicated varying materials
      composition across the sample and in the nanowires on the order of 20%. The use
      of modern synchrotron sources, where beam-sizes in the order of several 10 MUm
      are available, enables us to investigate compositional gradients along the sample
      by recording diffraction patterns at different positions. In addition,
      compositional variations were found also within single nanowires in X-ray energy
      dispersive spectroscopy measurements.

PMID- 24089581
TI  - Eating Expectancies in Relation to Eating Disorder Recovery.
AB  - This study examined the relation between eating expectancies, assessed via the
      Eating Expectancy Inventory, and eating disorder recovery. Individuals formerly
      seen for an eating disorder were categorized as having an active eating disorder
      (n = 53), as partially recovered (n = 15), or as fully recovered (n = 20). The
      expectancies of these groups were compared to each other and to 67 non-eating
      disorder controls. Results revealed that three of the five eating expectancies
      differed across groups. Non-eating disorder controls and fully recovered
      individuals endorsed similar levels of the expectancies that eating helps manage
      negative affect, eating is pleasurable and useful as a reward, and eating leads
      to feeling out of control. Partially recovered individuals looked more similar to
      active eating disorder cases on these expectancies. The other two expectancies
      did not differ across groups. Results provide some indication that certain eating
      expectancies may be associated with eating disorder recovery.

PMID- 24089582
TI  - Adolescent home-leaving and the transition to adulthood: A psychosocial and
      behavioural study in the slums of Nairobi.
AB  - Home-leaving is considered an important marker of the transition to adulthood and
      is usually framed as an individual decision. We move beyond this limited
      assumption to examine a broader conceptualization that might better illuminate
      home-leaving among youth in impoverished circumstances. We adopt the Problem
      Behavior Theory-framework to investigate the association of home-leaving with
      behavioral and psychosocial variables and with other transitions. We use data on
      adolescents aged 14-22 years from a three-wave study conducted between 2007 and
      2010. We used variable- and person-centered cross-sectional analyses, as well as
      predictive analysis of home-leaving by subsequent waves. Parental controls
      protection predicted home-leaving by subsequent waves. Overall, protective
      factors moderated the association of problem behavior involvement with leaving
      home in Nairobi's slums.

PMID- 24089583
TI  - Gender differences in rumination: A meta-analysis.
AB  - Starting in adolescence and continuing through adulthood, women are twice as
      likely as men to experience depression. According to the response styles theory
      (RST), gender differences in depression result, in part, from women's tendency to
      ruminate more than men. A meta-analysis was performed to evaluate gender
      differences in rumination in adults (k = 59; N = 14,321); additionally, an
      analysis of subtypes of rumination - brooding and reflection - was conducted (k =
      23). Fixed effects analyses indicated that women scored higher than men in
      rumination (d = .24, p < .01, SEd = .02), brooding (d = .19, p < .01, SEd = .03)
      and reflection (d = .17, p < .01, SEd = .03); there was no evidence of
      heterogeneity or publication bias across studies for these effect sizes. Although
      statistically significant, the effect sizes for gender differences in rumination
      were small in magnitude. Results are discussed with respect to the RST and gender
      differences in depression.

PMID- 24089584
TI  - The Timing of School Transitions and Early Adolescent Problem Behavior.
AB  - This longitudinal study investigates whether rural adolescents who transition to
      a new school in sixth grade have higher levels of risky behavior than adolescents
      who transition in seventh grade. Our findings indicate that later school
      transitions had little effect on problem behavior between sixth and ninth grades.
      Cross-sectional analyses found a small number of temporary effects of transition
      timing on problem behavior: Spending an additional year in elementary school was
      associated with higher levels of deviant behavior in the Fall of Grade 6 and
      higher levels of antisocial peer associations in Grade 8. However, transition
      effects were not consistent across waves and latent growth curve models found no
      effects of transition timing on the trajectory of problem behavior. We discuss
      policy implications and compare our findings with other research on transition
      timing.

PMID- 24089585
TI  - Variable Selection for Nonparametric Gaussian Process Priors: Models and
      Computational Strategies.
AB  - This paper presents a unified treatment of Gaussian process models that extends
      to data from the exponential dispersion family and to survival data. Our specific
      interest is in the analysis of data sets with predictors that have an a priori
      unknown form of possibly nonlinear associations to the response. The modeling
      approach we describe incorporates Gaussian processes in a generalized linear
      model framework to obtain a class of nonparametric regression models where the
      covariance matrix depends on the predictors. We consider, in particular,
      continuous, categorical and count responses. We also look into models that
      account for survival outcomes. We explore alternative covariance formulations for
      the Gaussian process prior and demonstrate the flexibility of the construction.
      Next, we focus on the important problem of selecting variables from the set of
      possible predictors and describe a general framework that employs mixture priors.
      We compare alternative MCMC strategies for posterior inference and achieve a
      computationally efficient and practical approach. We demonstrate performances on
      simulated and benchmark data sets.

PMID- 24089586
TI  - Correlation Structure of Fractional Pearson Diffusions.
AB  - The stochastic solution to a diffusion equations with polynomial coefficients is
      called a Pearson diffusion. If the first time derivative is replaced by a Caputo
      fractional derivative of order less than one, the stochastic solution is called a
      fractional Pearson diffusion. This paper develops an explicit formula for the
      covariance function of a fractional Pearson diffusion in steady state, in terms
      of Mittag-Leffler functions. That formula shows that fractional Pearson
      diffusions are long range dependent, with a correlation that falls off like a
      power law, whose exponent equals the order of the fractional derivative.

PMID- 24089587
TI  - Infliximab dose reduction sustains the clinical treatment effect in active HLAB27
      positive ankylosing spondylitis: a two-year pilot study.
AB  - The rationale of the study was to evaluate the efficacy of infliximab (IFX)
      treatment in patients with ankylosing spondylitis (AS) and to determine whether
      IFX dose reduction and interval extension sustains the treatment effect. Nineteen
      patients were included and treated with IFX 5 mg/kg every 6 weeks for 56 weeks.
      All patients concomitantly received MTX with median dose 7.5 mg/weekly. During
      the second year, the IFX dose was reduced to 3 mg/kg every 8 weeks. Eighteen
      patients completed the 1-year and 15 patients the 2-year trial. The >=50%
      improvement at week 16 from baseline of BASDAI was achieved in 16/19 (84%)
      patients. Significant reductions in BASDAI, BASFI, and BASMI scores, decrease in
      ESR and CRP, and improvement in SF-36 were observed at weeks 16 and 56. The MRI
      defined inflammatory changes in the sacroiliac joints disappeared in 10/15
      patients (67%) already at 16 weeks. IFX treatment effect was sustained throughout
      the second year after IFX dose reduction and interval extension. We conclude that
      IFX treatment is effective in well-established active AS and a dose reduction
      sustains the treatment effect. These observations are of clinical importance and
      open the opportunity to reduce the drug costs.

PMID- 24089588
TI  - Association between preoperative plasma sRAGE levels and recovery from cardiac
      surgery.
AB  - BACKGROUND: The receptor for advanced glycation end products (RAGE) is an
      inflammation-perpetuating receptor, and soluble RAGE (sRAGE) is a marker of
      cellular RAGE expression. This study investigated whether raised plasma levels
      prior to surgery of sRAGE or S100A8/A9 (a RAGE ligand) were associated with
      longer duration of hospital care in patients undergoing cardiac surgery
      necessitating cardiopulmonary bypass. METHODS: Patients (n = 130) undergoing
      elective cardiac surgery were enrolled prospectively. Plasma sRAGE and S100A8/A9
      concentrations were measured before and 2 h after surgery. RESULTS: Preoperative
      plasma sRAGE increased significantly (P < 0.0001) from 1.06 ng/mL (IQR, 0.72
      1.76) to 1.93 ng/mL (IQR, 1.14-2.63) 2 h postoperatively. Plasma S100A8/9 was
      also significantly (P < 0.0001) higher 2 h postoperatively (2.37  MU g/mL, IQR,
      1.81-3.05) compared to pre-operative levels (0.41  MU g/mL, IQR, 0.2-0.65).
      Preoperative sRAGE, but not S100A8/A9, was positively and significantly
      correlated with duration of critical illness (r = 0.3, P = 0.0007) and length of
      hospital stay (LOS; r = 0.31, P < 0.0005). Multivariate binary logistic
      regression showed preoperative sRAGE to be, statistically, an independent
      predictor of greater than median duration of critical illness (odds ratio 16.6, P
      = 0.014) and to be, statistically, the strongest independent predictor of
      hospital LOS. CONCLUSION: Higher preoperative plasma sRAGE levels were associated
      with prolonged duration of care in adults undergoing cardiac surgery requiring
      cardiopulmonary bypass.

PMID- 24089589
TI  - Strength training and testosterone treatment have opposing effects on migration
      inhibitor factor levels in ageing men.
AB  - BACKGROUND: The beneficial effects of testosterone treatment (TT) are debated.
      METHODS: Double-blinded, placebo-controlled study of six months TT (gel) in 54
      men aged 60-78 with bioavailable testosterone (BioT) <7.3 nmol/L and waist >94 cm
      randomized to TT (50-100 mg/day, n = 20), placebo (n = 18), or strength training
      (ST) (n = 16) for 24 weeks. Moreover, the ST group was randomized to TT (n = 7)
      or placebo (n = 9) after 12 weeks. OUTCOMES: Chemokines (MIF, MCP-1, and MIP-1
      alpha ) and lean body mass (LBM), total, central, extremity, visceral, and
      subcutaneous (SAT) fat mass established by DXA and MRI. Results. From 0 to 24
      weeks, MIF and SAT decreased during ST + placebo versus placebo, whereas BioT and
      LBM were unchanged. TT decreased fat mass (total, central, extremity, and SAT)
      and increased BioT and LBM versus placebo. MIF levels increased during TT versus
      ST + placebo. ST + TT decreased fat mass (total, central, and extremity) and
      increased BioT and LBM versus placebo. From 12 to 24 weeks, MCP-1 levels
      increased during TT versus placebo and MCP-1 levels decreased during ST + placebo
      versus placebo. CONCLUSION: ST + placebo was associated with decreased MIF levels
      suggesting decreased inflammatory activity. TT may be associated with increased
      inflammatory activity.

PMID- 24089591
TI  - From Knowledge Production to Implementation: Research Challenges and Imperatives.
AB  - As evidence-based practice is increasingly accepted in social work, the
      challenges associated with its actual implementation become more apparent and
      pressing. This article identifies implementation as a critical issue for
      research; implementation itself must be better understood if evidence-based
      practices are to be used and resultant improvements to practice are to be
      realized. Social work needs to engage more fully in (a) service system research
      and (b) implementation research, each of which complements and has potential to
      extend the benefits of efficacy and effectiveness research. Service system
      research can enhance the fit of empirically supported treatments to the needs of
      real-world practice and thus facilitate their implementation. Implementation
      studies examine the acceptability of evidence-based interventions, the
      feasibility and likelihood of their sustained use, and the decision-support
      procedures that can help practitioners apply probabilistically based, empirically
      supported treatments to the individual case in real-world practice.

PMID- 24089590
TI  - The involvement of phospholipases A2 in asthma and chronic obstructive pulmonary
      disease.
AB  - The increased morbidity, mortality, and ineffective treatment associated with the
      pathogenesis of chronic inflammatory diseases such as asthma and chronic
      obstructive pulmonary disease (COPD) have generated much research interest. The
      key role is played by phospholipases from the A2 superfamily: enzymes which are
      involved in inflammation through participation in pro- and anti-inflammatory
      mediators production and have an impact on many immunocompetent cells. The 30
      members of the A2 superfamily are divided into 7 groups. Their role in asthma and
      COPD has been studied in vitro and in vivo (animal models, cell cultures, and
      patients). This paper contains complete and updated information about the
      involvement of particular enzymes in the etiology and course of asthma and COPD. 

PMID- 24089592
TI  - Reporting vaccine complications: what do obstetricians and gynecologists know
      about the Vaccine Adverse Event Reporting System?
AB  - BACKGROUND: Obstetrician-gynecologists are increasingly called upon to be
      vaccinators as an essential part of a woman's primary and preventive health care.
      Despite the established safety of vaccines, vaccine adverse events may occur. A
      national Vaccine Adverse Event Reporting System (VAERS) is a well-established
      mechanism to track adverse events. However, we hypothesized that many
      obstetrician-gynecologists are naive to the role and use of VAERS. METHODS: We
      devised a ten-question survey to a sample of ACOG fellows to assess their
      knowledge and understanding of VAERS. We performed descriptive and frequency
      analysis for each of the questions and used one-way analysis of variance for
      continuous and chi-squared for categorical variables. RESULTS: Of the 1000
      fellows who received the survey, 377 responded. Only one respondent answered all
      nine knowledge questions correctly, and 9.2% of physicians had used VAERS. Older
      physicians were less familiar with VAERS in general and with the specific
      objectives of VAERS in particular (chi(2) = 10.7, P = .005). CONCLUSIONS:
      Obstetrician-gynecologist familiarity with VAERS is lacking. Only when the
      obstetrician-gynecologist is completely knowledgeable regarding standard vaccine
      practices, including the availability and use of programs such as VAERS, will
      providers be functioning as competent and complete vaccinators.

PMID- 24089593
TI  - Child and family characteristics influencing intervention choices in autism
      spectrum disorders.
AB  - A myriad of treatment options are available for children with autism, yet little
      is understood regarding characteristics of parents (e.g., education) and children
      (e.g., severity of autism symptoms) that influence types and amounts of therapy
      utilization. Interviews from 70 families were analyzed to determine potential
      influences on utilization (e.g., start of first services, use of traditional
      services). Descriptive findings regarding therapy types were similar to national
      studies. However, only three of the variables predicted utilization of specific
      therapies: severity of sensory processing problems was associated with earlier
      initiation of services in general, and higher maternal and paternal education was
      associated with the use of dietary and/or vitamin therapy as well as with more
      types of services. No other variables had predictive value; thus, the amount and
      type of therapies received may be more related to diagnostic practices and/or to
      the affordances/constraints of service delivery and reimbursement systems at
      particular ages.

PMID- 24089595
TI  - Reconsidering the emergence of social complexity in early Saharan pastoral
      societies, 5000 - 2500 B.C.
AB  - Debates on the subject of cultural complexity and its material manifestations are
      situated at the centre of research on prehistoric pastoralism in North Africa.
      Employing already published databases, this article integrates raw data from
      archaeological sites across the Sahara with ethnography to generate a framework
      of analysis in which changes in material culture can be interpreted. It attempts
      to establish a relationship between the analysis of human and cattle remains in
      order to study (a) the relations between modes of interment of animals and of
      humans, and social changes, and (b) the processes responsible for the appearance
      of a symbolism of power in the mid- and late Holocene funerary rituals. Their
      integration with landscape systems results in a conclusion of complex patterns of
      cultural diversity which question previous dismissals of early Saharan pastoral
      is is as the progenitors of social complexity.

PMID- 24089594
TI  - Radiation damage in protein serial femtosecond crystallography using an x-ray
      free-electron laser.
AB  - X-ray free-electron lasers deliver intense femtosecond pulses that promise to
      yield high resolution diffraction data of nanocrystals before the destruction of
      the sample by radiation damage. Diffraction intensities of lysozyme nanocrystals
      collected at the Linac Coherent Light Source using 2 keV photons were used for
      structure determination by molecular replacement and analyzed for radiation
      damage as a function of pulse length and fluence. Signatures of radiation damage
      are observed for pulses as short as 70 fs. Parametric scaling used in
      conventional crystallography does not account for the observed effects.

PMID- 24089596
TI  - Towards an archaeology of social organisation at Jebel Moya, 5th - 1st millennium
      BC.

PMID- 24089597
TI  - Low-temperature (10 degrees C) anaerobic digestion of dilute dairy wastewater in
      an EGSB bioreactor: microbial community structure, population dynamics, and
      kinetics of methanogenic populations.
AB  - The feasibility of anaerobic digestion of dairy wastewater at 10 degrees C was
      investigated in a high height : diameter ratio EGSB reactor. Stable performance
      was observed at an applied organic loading rate (OLR) of 0.5-2 kg COD m(-3) d(-1)
      with chemical oxygen demand (COD) removal efficiencies above 85%. When applied
      OLR increased to values above 2 kg COD m(-3) d(-1), biotreatment efficiency
      deteriorated, with methanogenesis being the rate-limiting step. The bioreactor
      recovered quickly (3 days) after reduction of the OLR. qPCR results showed a
      reduction in the abundance of hydrogenotrophic methanogenic Methanomicrobiales
      and Methanobacteriales throughout the steady state period followed by a sharp
      increase in their numbers (111-fold) after the load shock. Specific methanogenic
      activity and maximum substrate utilising rate (A(max)) of the biomass at the end
      of trial indicated increased activity and preference towards hydrogenotrophic
      methanogenesis, which correlated well with the increased abundance of
      hydrogenotrophic methanogens. Acetoclastic Methanosaeta spp. remained at stable
      levels throughout the trial. However, increased apparent half-saturation constant
      (K(m)) at the end of the trial indicated a decrease in the specific substrate
      affinity for acetate of the sludge, suggesting that Methanosaeta spp., which have
      high substrate affinity, started to be outcompeted in the reactor.

PMID- 24089598
TI  - Trajectories of Mothers' Discipline Strategies and Interparental Conflict:
      Interrelated Change during Middle Childhood.
AB  - Using data collected annually when children were in kindergarten through 3rd
      grade (N = 478), this study investigated changes in mothers' use of nonharsh,
      harsh verbal, and physical discipline; changes in interparental conflict; and
      associations between changes in discipline and interparental conflict.
      Controlling for potential confounds, physical discipline decreased over the
      course of middle childhood, whereas harsh verbal and nonharsh discipline remained
      stable. Increases in interparental conflict were associated with increases in
      physical discipline; decreases in interparental conflict were associated with
      decreases in physical discipline. Change in interparental conflict was unrelated
      to change in harsh verbal or nonharsh discipline, although more frequent
      interparental conflict was associated with more frequen10t use of all three types
      of discipline in 1st grade. Findings extend previous research on how two major
      forms of communication within families-conflict between parents and parents'
      attempts to influence their children through discipline-change across middle
      childhood.

PMID- 24089600
TI  - Ultrasound-assisted extraction of total phenolic compounds from Inula helenium.
AB  - Ultrasound-assisted extraction (UAE) of phenolic compounds from Inula helenium
      was studied. Effects of ethanol concentration, ultrasonic time, solid-liquid
      ratio, and number of extractions were investigated. An orthogonal array was
      constructed to optimize UAE process. The optimized extraction conditions were as
      follows: ethanol concentration, 30%; solid-liquid ratio, 1 : 20; number of
      extractions, 2 times; extraction time, 30 min. Under the optimal conditions, the
      yield of total phenolic compounds and chlorogenic acid was 6.13 +/- 0.58 and 1.32
      +/- 0.17 mg/g, respectively. The results showed that high amounts of phenolic
      compounds can be extracted from I. helenium by ultrasound-assisted extraction
      technology. 

PMID- 24089599
TI  - Evaluation of antioxidant, immunomodulatory, and cytotoxic action of fractions
      from Eugenia uniflora L. and Eugenia malaccensis L.: correlation with polyphenol
      and flavanoid content.
AB  - An increasing number of biological activities presented by medicinal plants has
      been investigated over the years, and they are used in the search for new
      substances with lower side effects. Eugenia uniflora L. and Eugenia malaccensis
      L. (Myrtaceae) have many folk uses in various countries. This current study was
      designed to quantify the polyphenols and flavonoids contents and evaluate the
      immunomodulatory, antioxidant, and cytotoxic potentials of fractions from E.
      uniflora L. and E. malaccensis L. It was observed that the polyphenol content was
      higher in ethyl acetate fractions. These fractions have high antioxidant
      potential. E. malaccensis L. seeds showed the largest DPPH radical scavenger
      capacity (EC50 = 22.62). The fractions of E. malaccensis L. leaves showed lower
      antioxidant capacity. The samples did not alter the profile of proinflammatory
      cytokines and nitric oxide release. The results indicate that species of the
      family Myrtaceae are rich in compounds with antioxidant capacity, which can help
      reduce the inflammatory response. 

PMID- 24089601
TI  - Why is ABI effective in detecting vascular stenosis? Investigation based on
      multibranch hemodynamic model.
AB  - The ankle-brachial index (ABI), defined as the ratio of systolic pressure in the
      ankle arteries and that in the brachial artery, was a useful noninvasive method
      to detect arterial stenoses. There had been a lot of researches about clinical
      regularities of ABI; however, mechanism studies were less addressed. For the
      purpose of a better understanding of the correlation between vascular stenoses
      and ABI, a computational model for simulating blood pressure and flow propagation
      in various arterial stenosis circumstances was developed with a detailed
      compartmental description of the heart and main arteries. Particular attention
      was paid to the analysis of effects of vascular stenoses in different large-sized
      arteries on ABI in theory. Moreover, the variation of ABI during the increase of
      the stenosis severity was also studied. Results showed that stenoses in lower
      limb arteries, as well as, brachial artery, caused different variations of blood
      pressure in ankle and brachial arteries, resulting in a significant change of
      ABI. Furthermore, the variation of ABI became faster when the severity of the
      stenosis increased, validating that ABI was more sensitive to severe stenoses
      than to mild/moderate ones. All these in findings revealed the reason why ABI was
      an effective index for detecting stenoses, especially in lower limb arteries. 

PMID- 24089602
TI  - Clinical significance of preoperative neutrophil lymphocyte ratio versus platelet
      lymphocyte ratio in patients with small cell carcinoma of the esophagus.
AB  - Recent studies have shown that the presence of systemic inflammation correlates
      with poor survival in various of cancers. The aim of this study was to determine
      the prognostic values of neutrophil lymphocyte ratio (NLR) and platelet
      lymphocyte ratio (PLR) in patients with small cell carcinoma of the esophagus
      (SCCE). Preoperative NLR and PLR were evaluated in 43 patients with SCCE from
      January 2001 to December 2010. The prognostic significance of both markers was
      then determined by both uni- and multivariate analytical methods. Receiver
      operating characteristic (ROC) curves were also plotted to verify the accuracy of
      NLR and PLR for survival prediction. Patients with PLR >=150 had significantly
      poorer (relapse-free survival) RFS and (overall survival) OS compared to patients
      with PLR <150. However, RFS or OS did not differ according to NLR categories
      (<3.5 and >=3.5). The areas under the curve (AUC) indicated that PLR was superior
      to NLR as a predictive factor. The results of the present study conclude that PLR
      is superior to NLR as a predictive factor in patients with SCCE. 

PMID- 24089603
TI  - The chamber for studying rice response to elevated nighttime temperature in
      field.
AB  - An in situ temperature-controlled field chamber was developed for studying a
      large population of rice plant under different nighttime temperature treatments
      while maintaining conditions similar to those in the field during daytime. The
      system consists of a pipe hoop shed-type chamber with manually removable covers
      manipulated to provide a natural environment at daytime and a relatively stable
      and accurate temperature at night. Average air temperatures of 22.4 +/- 0.3
      degrees C at setting of 22 degrees C, 27.6 +/- 0.4 degrees C at 27 degrees C, and
      23.8 +/- 0.7 degrees C ambient conditions were maintained with the system. No
      significant horizontal and vertical differences in temperature were found and
      only slight changes in water temperatures were observed between the chambers and
      ambient conditions at 36 days after transplanting. A slight variation in CO2
      concentration was observed at the end of the treatment during the day, but the 10
      MUmol CO2 mol-1 difference was too small to alter plant response. The present
      utilitarian system, which only utilizes an air conditioner/heater, is suitable
      for studying the effect of nighttime temperature on plant physiological responses
      with minimal perturbation of other environmental factors. At the same time, it
      will enable in situ screening of many rice genotypes.

PMID- 24089604
TI  - Octagonal defects at carbon nanotube junctions.
AB  - We investigate knee-shaped junctions of semiconductor zigzag carbon nanotubes.
      Two dissimilar octagons appear at such junctions; one of them can reconstruct
      into a pair of pentagons. The junction with two octagons presents two degenerate
      localized states at Fermi energy (E(F)). The reconstructed junction has only one
      state near E(F), indicating that these localized states are related to the
      octagonal defects. The inclusion of Coulomb interaction splits the localized
      states in the junction with two octagons, yielding an antiferromagnetic system.

PMID- 24089605
TI  - Safety analysis using Lebesgue strain measure of thick-walled cylinder for
      functionally graded material under internal and external pressure.
AB  - Safety analysis has been done for thick-walled circular cylinder under internal
      and external pressure using transition theory which is based on the concept of
      generalized principal Lebesgue strain measure. Results have been analyzed
      theoretically and discussed numerically. From the analysis, it can be concluded
      that circular cylinder made of functionally graded material is on the safer side
      of the design as compared to homogeneous cylinder with internal and external
      pressure, which leads to the idea of "stress saving" that minimizes the
      possibility of fracture of cylinder. 

PMID- 24089607
TI  - Optimization and thermoeconomics research of a large reclaimed water source heat
      pump system.
AB  - This work describes a large reclaimed water source heat pump system (RWSHPS) and
      elaborates on the composition of the system and its design principles. According
      to the characteristics of the reclaimed water and taking into account the initial
      investment, the project is divided into two stages: the first stage adopts
      distributed heat pump heating system and the second adopts the combination of
      centralized and decentralized systems. We analyze the heating capacity of the
      RWSHPS, when the phase II project is completed, the system can provide hydronic
      heating water with the supply and return water temperature of 55 degrees C/15
      degrees C and meet the hydronic heating demand of 8 million square meters of
      residential buildings. We make a thermal economics analysis by using Thermal
      Economics theory on RWSHPS and gas boiler system, it is known that the RWSHPS has
      more advantages, compared with the gas boiler heating system; both its thermal
      efficiency and economic efficiency are relatively high. It provides a reference
      for future applications of the RWSHPS. 

PMID- 24089608
TI  - Using Xpert MTB/RIF.
AB  - Xpert MTB/RIF is an automated real-time polymerase chain reaction test for
      simultaneous detection of tuberculosis and rifampicin resistance. Xpert MTB/RIF
      has demonstrated excellent accuracy in clinical evaluation studies, but has
      reduced sensitivity for detection of smear-negative tuberculosis. Since sample
      processing and detection are largely automated, Xpert MTB/RIF is potentially
      suitable for implementation in resource-limited settings. There are, however, a
      number of practical constraints to the use of Xpert at the point-of-care. Xpert
      remains a relatively costly test, and clear demonstration of cost-effectiveness
      will be needed to support efforts to scale up testing in high burden countries.

PMID- 24089609
TI  - Weight loss and melatonin reduce obesity-induced oxidative damage in rat testis.
AB  - Aim. We aimed to evaluate the antioxidant effects of weight loss and melatonin on
      the obesity-induced oxidative damage in rat testes. Materials and Methods. 28
      male Wistar albino rats were randomly divided into 4 groups, each consisting of 7
      rats: control group (Group 1), obesity group (Group 2), obesity + MLT group
      (Group 3), and weight loss group (Group 4). Rats were weighed at the beginning
      and at the end of the study. Bilateral orchiectomy was performed and 5 cc blood
      samples were obtained from all of the rats. Superoxide dismutase (SOD),
      malondialdehyde (MDA), and protein carbonyl (PC) levels were analysed in the
      testicular tissues and serum. Spermatogenesis was evaluated with the Johnsen
      scoring system. Results. The testicular tissue and serum levels of MDA, PC, and
      SOD activity were increased in the obesity group in comparison to the sham
      operated group (P < 0.05). Weight loss and melatonin treatment ameliorated MDA,
      PC, and SOD levels in testicular tissue and serum significantly (P < 0.05). There
      was no significant difference between groups in terms of mean Johnsen score (P =
      0.727). Conclusion. Experimentally created obesity caused oxidative stress and
      both melatonin and weight loss reduced oxidative stress parameters in rat testes.

PMID- 24089610
TI  - Relationship between Testicular Volume and Conventional or Nonconventional Sperm
      Parameters.
AB  - Background. Reduced testicular volume (TV) (<12 cm(3)) is associated with lower
      testicular function. Several studies explored the conventional sperm parameters
      (concentration, motility, and morphology) and the endocrine function
      (gonadotropins and testosterone serum concentrations) in the patients with
      reduction of TV. No other parameters have been examined. Aim. This study aims at
      evaluating some biofunctional sperm parameters by flow cytometry in the semen of
      men with reduced TV compared with that of subjects with normal TV. Methods. 78
      patients without primary scrotal disease were submitted to ultrasound evaluation
      of the testis. They were divided into two groups according to testicular volume:
      A Group, including 40 patients with normal testicular volume (TV > 15 cm(3)) and
      B Group, including 38 patients with reduced testicular volume (TV <= 12 cm(3)).
      All patients underwent serum hormone concentration, conventional and
      biofunctional (flow cytometry) sperm parameters evaluation. Results. With regard
      to biofunctional sperm parameters, all values (mitochondrial membrane potential,
      phosphatidylserine externalization, chromatin compactness, and DNA fragmentation)
      were strongly negatively correlated with testicular volume (P < 0.0001).
      Conclusions. This study for the first time in the literature states that the
      biofunctional sperm parameters worsen and with near linear correlation, with
      decreasing testicular volume. 

PMID- 24089611
TI  - Fish and marine omega-3 polyunsatured Fatty Acid consumption and incidence of
      type 2 diabetes: a systematic review and meta-analysis.
AB  - Objective. To examine the association between fish and marine long-chain omega-3
      polyunsaturated fatty acid (LC n-3 PUFA) consumption and incidence of type 2
      diabetes (T2D) in prospective cohort studies. Methods. Meta-analytic procedures
      were used to estimate the relative risk (RR) using random effects or fixed
      effects generic inverse variance model. Publication bias and study heterogeneity
      were assessed using Egger's test and I(2) statistic. Results. We found no
      significant association between the intake of fish/seafood (pooled RR: 1.04; P =
      0.63, 95% CI: 0.9 to 1.2, 549, 955 participants) or marine LC n-3 PUFA (pooled
      RR: 1.08, P = 0.39, 95% CI: 0.90 to 1.30, 346, 710 participants) and T2D risk.
      Significant study heterogeneity was observed in fish/seafood and marine LC n-3
      PUFA studies (P < 0.00001). Subgroup analysis revealed no obvious sources for
      high heterogeneity. We also found a significant protective effect of oily fish
      intake on T2D risk (pooled RR = 0.89, P = 0.005, 95% CI: 0.82 to 0.96). Dose
      response analysis suggested that every 80 g per day intake of oily fish may
      reduce 20% risk of T2D. Conclusion. We found no significant effect of
      fish/seafood or marine LC n-3 PUFA intake on risk of T2D but a significant effect
      of oily fish intake on risk of T2D. 

PMID- 24089612
TI  - Enhanced healing of diabetic wounds by subcutaneous administration of human
      umbilical cord derived stem cells and their conditioned media.
AB  - Objective. Mesenchymal stem cells (MSCs) isolated from the umbilical cord and
      their conditioned media (CM) can be easily obtained and refined compared with
      stem cells from other sources. Here, we explore the possibility of the benefits
      of these cells in healing diabetic wounds. Methodology and Results. Delayed wound
      healing animal models were established by making a standard wound on the dorsum
      of eighteen db/db mice, which were divided into three groups with six mice in
      each: groups I, II, and III received PBS, UC-MSC, and CM, respectively. UC-MSC
      and their CM significantly accelerated wound closure compared to PBS-treated
      wounds, and it was most rapid in CM-injected wounds. In day-14 wounds,
      significant difference in capillary densities among the three groups was noted (n
      = 6; P < 0.05), and higher levels of VEGF, PDGF, and KGF expression in the CM-
      and UC-MSC-injected wounds compared to the PBS-treated wounds were seen. The
      expression levels of PDGF- beta and KGF were higher in CM-treated wounds than
      those in UC-MSC-treated wounds. Conclusion. Both the transplantation of UC-MSC
      and their CM are beneficial to diabetic wound healing, and CM has been shown to
      be therapeutically better than UC-MSC, at least in the context of diabetic wound
      healing. 

PMID- 24089613
TI  - Renal Effects of DPP-4 Inhibitors: A Focus on Microalbuminuria.
AB  - Incretin-based therapies represent one of the most promising options in type 2
      diabetes treatment owing to their good effectiveness with low risk of
      hypoglycemia and no weight gain. Other numerous potential beneficial effects of
      incretin-based therapies have been suggested based mostly on experimental and
      small clinical studies including its beta-cell- and vasculo-protective actions.
      One of the recently emerged interesting features of dipeptidyl peptidase-4 (DPP
      4) inhibitors is its possible protective effect on the diabetic kidney disease.
      Here, we review the renal effects of DPP-4 inhibitors with special focus on its
      influence on the onset and progression of microalbuminuria, as presence of
      microalbuminuria represents an important early sign of kidney damage and is also
      associated with increased risk of hypoglycemia and cardiovascular complications.
      Mechanisms underlying possible nephroprotective properties of DPP-4 inhibitors
      include reduction of oxidative stress and inflammation and improvement of
      endothelial dysfunction. Effects of DPP-4 inhibitors may be both glucagon-like
      peptide-1 (GLP-1) dependent and independent. Ongoing prospective studies focused
      on the nephroprotective effects of DPP-4 inhibitors will further clarify its
      possible role in the prevention/attenuation of diabetic kidney disease beyond its
      glucose lowering properties. 

PMID- 24089614
TI  - Computerized tomography technique for the investigation of the maxillary first
      molar mesiobuccal root.
AB  - The aim of this paper was to review the literature about the use of computerized
      tomography to evaluate the presence and characteristics of the second mesiobuccal
      canal in the maxillary first molar. An electronic search was performed.
      Frequencies of the presence of second mesiobuccal canal and root anatomy
      characteristics were extracted from the selected studies. Pooled frequencies were
      calculated as weighted means. Seven articles were included. A second mesiobuccal
      canal was present in 59.32% of the teeth, and it was noncommunicating in 58.45%
      of teeth presenting the canal itself. The most common root canal morphology was
      single canal or two separated canals. The present paper showed that cone beam CT
      is a viable radiologic device for the evaluation of the mesiobuccal root of
      maxillary first molars. In fact, it was observed that the frequency of second
      mesiobuccal canal detection is similar to those presented by clinical studies or
      micro-CT evaluations. 

PMID- 24089615
TI  - Disinfection of dental unit water line using aloe vera: in vitro study.
AB  - Context. Dental unit waterlines may be heavily contaminated with microorganisms
      and are a potential source of infection for both practicing staff and
      immunocompromised patients particularly. Contamination of dental unit water lines
      could be inhibited with the use of disinfectants. The present study investigates
      the effect of aloe-vera-based disinfectant in reducing the microbial growth in
      dental unit water lines (DUWLs). Aims. To compare the efficacy of aloe vera,
      hydrogen peroxide (H2O2), and 5% sodium hypochlorite (NaOCl) in controlling
      microbial contamination of DUWLs. Materials and Methods. After obtaining baseline
      water samples, the dental unit waterlines were treated with aloe vera, 10%
      hydrogen peroxide, and 5% sodium hypochlorite. Each of the three disinfectants
      was used in increasing concentrations and their inhibiting effect was compared.
      Water samples were analyzed for microbiological quality by the total viable count
      (TVC) method. Statistical Analysis Used. SPSS 16. Results. There was significant
      reduction in mean CFU/ml when treated with disinfectants each for a period of one
      week. Aloe-vera solution was found to be the most effective in reducing the
      microbial colonies. Conclusions. Improving the water quality from dental unit
      water lines is of considerable importance; chemical-based disinfectants can be
      replaced with herbal disinfectants for treating microbial contamination in dental
      unit waterlines. 

PMID- 24089616
TI  - Evolving Bioprosthetic Tissue Calcification Can Be Quantified Using Serial
      Multislice CT Scanning.
AB  - Background. We investigated the value of serial multislice CT scanning for in
      vivo determination of evolving tissue calcification in three separate
      experimental settings. Materials and Methods. Bioprosthetic valve tissue was
      implanted in three different conditions: (1) glutaraldehyde-fixed porcine
      stentless conduits in pulmonary position (n = 6); (2) glutaraldehyde-fixed
      stented pericardial valves in mitral position (n = 3); and (3) glutaraldehyde
      fixed pericardial tissue as patch in the jugular vein and carotid artery (n =
      16). Multislice CT scanning was performed at various time intervals. Results. In
      stentless conduits, the distribution of wall calcification can be reliably
      quantified with CT. After 20 weeks, the CT-determined mean calcium volume was
      1831 +/- 581 mm3, with a mean wall calcium content of 89.8 +/- 44.4  MU g/mg (r
      (2) = 0.68). In stented pericardial valves implanted in mitral position, reliable
      determination of tissue mineralization is disturbed by scattering caused by the
      (continuously moving) alloy of the stent material. Pericardial patches in the
      neck vessels revealed progressive mineralization, with a significant increase in
      mean HU and calcium volume at 8 weeks after implantation, rising up to a level of
      131.1 +/- 39.6 mm3 (mean calcium volume score) and a mean calcium content of 19.1
      +/- 12.3  MU g/mg. Conclusion. The process of bioprosthetic tissue mineralization
      can be visualized and quantified in vivo using multislice CT scanning. This
      allows determination of the kinetics of tissue mineralization with intermediate
      in vivo evaluations. 

PMID- 24089617
TI  - Disease activity measures in paediatric rheumatic diseases.
AB  - Disease activity refers to potentially reversible aspects of a disease.
      Measurement of disease activity in paediatric rheumatic diseases is a critical
      component of patient care and clinical research. Disease activity measures are
      developed systematically, often involving consensus methods. To be useful, a
      disease activity measure must be feasible, valid, and interpretable. There are
      several challenges in quantifying disease activity in paediatric rheumatology;
      namely, the conditions are multidimensional, the level of activity must be
      valuated in the context of treatment being received, there is no gold standard
      for disease activity, and it is often difficult to incorporate the patient's
      perspective of their disease activity. To date, core sets of response variables
      are defined for juvenile idiopathic arthritis, juvenile systemic lupus
      erythematosus, and juvenile dermatomyositis, as well as definitions for
      improvement in response to therapy. Several specific absolute disease activity
      measures also exist for each condition. Further work is required to determine the
      optimal disease activity measures in paediatric rheumatology. 

PMID- 24089618
TI  - Visceral leishmaniasis with associated common, uncommon, and atypical
      morphological features on bone marrow aspirate cytology in nonendemic region.
AB  - Objectives. The present study was conducted to categorise the morphological
      features on bone marrow aspirate cytology into common, uncommon, and atypical
      features in a nonendemic region which would be helpful in clinching an early and
      correct diagnosis especially in clinically unsuspected cases. Methods. The
      morphological features on bone marrow were categorized into common, uncommon, and
      atypical in cases of leishmaniasis from non endemic region. Results. Out of total
      27 cases, 77.7% were residents of places at the height of 500 m or above and
      fever was the most common presentation followed by hepatosplenomegaly.
      Plasmacytosis, hemophagocytosis were the common cytological features while
      dysmyelopoiesis, presence of leishmania bodies in nonhistiocytic cells, and
      granuloma with necrosis were uncommon features. Aggregates of LD bodies in form
      of ring, floret, or strap shapes along with giant cells constitute the atypical
      morphological features. Conclusion. The knowledge of common, uncommon, and
      atypical features on bone marrow aspirate cytology is helpful in clinching an
      early and correct diagnosis of leishmaniasis especially in non endemic areas
      where clinical suspicion is low. These features will guide the pathologist for
      vigilant search of LD bodies in the marrow for definite diagnosis and thus will
      also be helpful in preventing unnecessary workups. 

PMID- 24089619
TI  - Factors Associated with the Use of Different Treatment Modalities among Patients
      with Upper Airway Diseases in Taiwan: A Cross-Sectional Survey Study.
AB  - Rhinitis is a common upper airway disease and can have great impact on patients'
      quality of life. Factors associated with the use of common treatment modalities
      among 279 Taiwanese rhinitis patients from the outpatient department of
      otolaryngology in a medical center were investigated using a cross-sectional
      survey study. Results from multiple logistic regression analysis, adjusted for
      etiologies of rhinitis, revealed that males were associated with surgical
      intervention (OR = 2.11, P = 0.009). Lower educational level was associated with
      oral (OR = 2.31, P = 0.024) and topical medications (OR = 2.50, P = 0.005). Poor
      or fair general health status was associated with topical medications (OR = 4.47,
      P = 0.001), whereas very good or excellent general health status was inversely
      associated with surgical intervention (OR = 0.32, P = 0.002). Smoking was
      associated with the use of nasal irrigation (OR = 2.72, P = 0.003). Worse disease
      specific quality of life was associated with oral medications (OR = 2.46, P =
      0.010) and traditional Chinese medicine (OR = 5.43, P < 0.001). In conclusion,
      the use of different treatment modalities for rhinitis was associated with
      different combinations of independent factors. 

PMID- 24089620
TI  - Active commuting among K-12 educators: a study examining walking and biking to
      work.
AB  - BACKGROUND: Walking and biking to work, active commuting (AC) is associated with
      many health benefits, though rates of AC remain low in the US. K-12 educators
      represent a significant portion of the workforce, and employee health and
      associated costs may have significant economic impact. Therefore, the purpose of
      this study was to examine the current rates of AC and factors associated with AC
      among K-12 educators. METHODS: A volunteer sample of K-12 educators (n = 437) was
      recruited to participate in an online survey. Participants responded about AC
      patterns and social ecological influences on AC (individual, interpersonal,
      institutional, community, and environmental factors). t-tests and ANOVAs examined
      trends in AC, and Pearson correlations examined the relationship between AC and
      dependent variables. Multiple regression analysis determined the relative
      influence of individual, interpersonal, institutional, community, and
      environmental levels on AC. RESULTS: Participants actively commuted 0.51 +/- 1.93
      times/week. There were several individual, interpersonal, institutional,
      community, and environmental factors significantly related to AC. The full model
      explained 60.8% of the variance in AC behavior. CONCLUSIONS: This study provides
      insight on the factors that determine K-12 educators mode of commute and provide
      some insight for employee wellness among this population.

PMID- 24089621
TI  - Blockade of Adrenal Medulla-Derived Epinephrine Potentiates Bee Venom-Induced
      Antinociception in the Mouse Formalin Test: Involvement of Peripheral beta 
      Adrenoceptors.
AB  - The injection of diluted bee venom (DBV) into an acupoint has been used
      traditionally in eastern medicine to treat a variety of inflammatory chronic pain
      conditions. We have previously shown that DBV had a potent antinociceptive
      efficacy in several rodent pain models. However, the peripheral mechanisms
      underlying DBV-induced antinociception remain unclear. The present study was
      designed to investigate the role of peripheral epinephrine on the DBV-induced
      antinociceptive effect in the mouse formalin assay. Adrenalectomy significantly
      enhanced the antinociceptive effect of DBV during the late phase of the formalin
      test, while chemical sympathectomy had no effect. Intraperitoneal injection of
      epinephrine blocked this adrenalectomy-induced enhancement of the DBV-induced
      antinociceptive effect. Moreover, injection of a phenylethanolamine N
      methyltransferase (PNMT) inhibitor enhanced the DBV-induced antinociceptive
      effect. Administration of nonselective beta -adrenergic antagonists also
      significantly potentiated this DBV-induced antinociception, in a manner similar
      to adrenalectomy. These results demonstrate that the antinociceptive effect of
      DBV treatment can be significantly enhanced by modulation of adrenal medulla
      derived epinephrine and this effect is mediated by peripheral beta 
      adrenoceptors. Thus, DBV acupoint stimulation in combination with inhibition of
      peripheral beta -adrenoceptors could be a potentially novel strategy for the
      management of inflammatory pain. 

PMID- 24089622
TI  - Ethnomedicinal practices for treating liver disorders of local communities in the
      southern regions of Korea.
AB  - This study aims to analyze and record ethnomedicinal practices for treating liver
      disorders of residents living in local communities in the southern regions of
      Korea. Data was collected using participant observations and in-depth interviews,
      as the informants also become investigators themselves through attending informal
      meetings, open and group discussions, and overt observations with semistructured
      questionnaires. In this study, ethnomedicinal practices for liver ailments were
      recorded by 1,543 informants (362 men, 1,181 women) at 160 sites. The kinds of
      liver disorders treated by ethnomedicinal practices were liver cancer, liver
      cirrhosis, jaundice, hepatitis, fatigue recovery, hangovers, and liver-related
      ailments. The category with the highest degree of consensus from the informants
      was jaundice (0.95), and the lowest degree of consensus was for liver cancer and
      liver cirrhosis (0.61). According to fidelity levels, 28 species resulted in
      fidelity levels of 100%. The internetwork analysis was first applied for the
      interpretation of ethnomedicinal knowledge of a community, although it has been
      strictly used until now for social science in the analysis of social trends and
      phenomena through the interrelationship of specific components. 

PMID- 24089623
TI  - Cross-Linked Fiber Network Embedded in Elastic Matrix.
AB  - The mechanical behavior of a three-dimensional cross-linked fiber network
      embedded in matrix is studied in this work. The network is composed from linear
      elastic fibers which store energy only in the axial deformation mode, while the
      matrix is also isotropic and linear elastic. Such systems are encountered in a
      broad range of applications, from tissue to consumer products. As the matrix
      modulus increases, the network is constrained to deform more affinely. This leads
      to internal forces acting between the network and the matrix, which produce
      strong stress concentration at the network cross-links. This interaction
      increases the apparent modulus of the network and decreases the apparent modulus
      of the matrix. A model is developed to predict the effective modulus of the
      composite and its predictions are compared with numerical data for a variety of
      networks.

PMID- 24089625
TI  - Alloying and Structure of Ultrathin Gallium Films on the (111) and (110) Surfaces
      of Palladium.
AB  - Growth, thermal stability, and structure of ultrathin gallium films on Pd(111)
      and Pd(110) are investigated by low-energy ion scattering and low-energy electron
      diffraction. Common to both surface orientations are growth of disordered Ga
      films at coverages of a few monolayers (T = 150 K), onset of alloy formation at
      low temperatures (T ~ 200 K), and formation of a metastable, mostly disordered
      1:1 surface alloy at temperatures around 400-500 K. At higher temperatures a Ga
      surface fraction of ~0.3 is slightly stabilized on Pd(111), which we suggest to
      be related to the formation of Pd2Ga bulk-like films. While on Pd(110) only a Pd
      up/Ga-down buckled surface was observed, an inversion of buckling was observed on
      Pd(111) upon heating. Similarities and differences to the related Zn/Pd system
      are discussed.

PMID- 24089626
TI  - Comparing statistical methods for removing seasonal variation from vitamin D
      measurements in case-control studies.
AB  - Vitamin D deficiency has been shown to be associated with multiple clinical
      outcomes, including osteoporosis, multiple sclerosis and colorectal cancer. In
      studies of vitamin D effect on disease outcome, vitamin D status is usually
      measured by a serum biomarker, namely 25-hydroxy vitamin D [25(OH)D]. Since the
      circulating 25(OH)D concentration varies from season to season and not all blood
      samples are collected at the same time, the disease-vitamin D relationship can be
      obscured if the seasonal variation is not adjusted properly. In the literature, a
      two-step procedure is usually adopted, with the vitamin D level adjusted for the
      seasonal variation being obtained in the first step, and the effect of vitamin D
      being assessed based on the adjusted vitamin D level at the second step. This two
      step method can generate misleading results as the estimation variance arising
      from the first step is not taken into account in the second step analysis. We
      consider three alternative procedures that unify the two steps into a single
      model. We conduct an extensive simulation study to evaluate the performance of
      these methods and demonstrate their applications in a study of 25(OH)D effect on
      prostate cancer risk.

PMID- 24089624
TI  - Adenosine kinase is a new therapeutic target to prevent ischemic neuronal death.
AB  - The brain has evolved several endogenous mechanisms to protect itself from the
      deleterious consequences of stroke. One of those endogenous neuroprotective
      systems is centered on the purine ribonucleoside adenosine, which exerts potent
      neuroprotective functions within the brain. One major goal in therapeutic stroke
      research is to explore and utilize such endogenous neuroprotective mechanisms
      therapeutically. This review illustrates molecular approaches to study the role
      of the adenosine system within the context of stroke and highlights innovative
      therapeutic approaches aimed at increasing adenosinergic function. New research
      data suggest that the major adenosine regulating enzyme adenosine kinase (ADK)
      plays a prominent role in determining the brain's susceptibility to ischemic
      injury. Thus, endogenous ADK is rapidly downregulated following a stroke,
      possibly an endogenous neuroprotective mechanism aimed at raising ambient levels
      of adenosine in brain. Conversely, transgenic overexpression of ADK in brain
      renders the brain more susceptible to stroke-induced neuronal cell loss. In the
      present review we will first summarize the physiological role of adenosine
      metabolism within the context of ischemic brain injury. Next, we will highlight
      the key role of ADK in determining the brain's susceptibility to ischemic injury,
      and finally we will discuss potential therapeutic applications of adenosine
      augmentation to provide neuroprotection in stroke.

PMID- 24089627
TI  - How to estimate the measurement error variance associated with ancestry
      proportion estimates.
AB  - To show how the variance of the measurement error (ME) associated with individual
      ancestry proportion estimates can be estimated, especially when the number of
      ancestral populations (k) is greater than 2. We extend existing internal
      consistency measures to estimate the ME variance, and we compare these estimates
      with the ME variance estimated by use of the repeated measurement (RM) approach.
      Both approaches work by dividing the genotyped markers into subsets. We examine
      the effect of the number of subsets and of the allocation of markers to each
      subset on the performance of each approach. We used simulated data for all
      comparisons. Independently of the value of k, the measures of internal
      reliability provided less biased and more precise estimates of the ME variance
      than did those obtained with the RM approach. Both methods tend to perform better
      when a large number of subsets of markers with similar sizes are considered. Our
      results will facilitate the use of ME correction methods to address the ME
      problem in individual ancestry proportion estimates. Our method will improve the
      ability to control for type I error inflation and loss of power in association
      tests and other genomic research involving ancestry estimates.

PMID- 24089630
TI  - Lack of HXK2 induces localization of active Ras in mitochondria and triggers
      apoptosis in the yeast Saccharomyces cerevisiae.
AB  - We recently showed that activated Ras proteins are localized to the plasma
      membrane and in the nucleus in wild-type cells growing exponentially on glucose,
      while in the hxk2Delta strain they accumulated mainly in mitochondria. An
      aberrant accumulation of activated Ras in these organelles was previously
      reported and correlated to mitochondrial dysfunction, accumulation of ROS, and
      cell death. Here we show that addition of acetic acid to wild-type cells results
      in a rapid recruitment of Ras-GTP from the nucleus and the plasma membrane to the
      mitochondria, providing a further proof that Ras proteins might be involved in
      programmed cell death. Moreover, we show that Hxk2 protects against apoptosis in
      S. cerevisiae. In particular, cells lacking HXK2 and showing a constitutive
      accumulation of activated Ras at the mitochondria are more sensitive to acetic
      acid-induced programmed cell death compared to the wild type strain. Indeed,
      deletion of HXK2 causes an increase of apoptotic cells with several morphological
      and biochemical changes that are typical of apoptosis, including DNA
      fragmentation, externalization of phosphatidylserine, and ROS production.
      Finally, our results suggest that apoptosis induced by lack of Hxk2 may not
      require the activation of Yca1, the metacaspase homologue identified in yeast. 

PMID- 24089629
TI  - Protective effects of extracts from Fructus rhodomyrti against oxidative DNA
      damage in vitro and in vivo.
AB  - OBJECTIVE: To evaluate the potential protective effects of extracts from Fructus
      rhodomyrti (FR) against oxidative DNA damage using a cellular system and the
      antioxidant ability on potassium bromate- (KBrO3-) mediated oxidative stress in
      rats. METHODS: The effects of FR on DNA damage induced by hydrogen peroxide
      (H2O2) were evaluated by comet assay in primary spleen lymphocytes cultures. The
      effects of FR on the activities of SOD, CAT, and GPx and the levels of GSH,
      hydroperoxides, and 8-OHdG were determined in the plasma and tissues of rats
      treated with KBrO3. RESULTS: FR was shown to effectively protect against DNA
      damage induced by H2O2  in vitro, and the maximum protective effect was observed
      when FR was diluted 20 times. Endogenous antioxidant status, namely, the
      activities of SOD, CAT, and GPx and the levels of GSH were significantly
      decreased in the plasma, the liver, and the kidney of the KBrO3-treated rats,
      while the pretreatment of FR prevented the decreases of these parameters. In
      addition, the pretreatment of FR was also able to prevent KBrO3-induced increases
      in the levels of hydroperoxides and 8-OHdG in the plasma, the liver, and the
      kidney in rats. CONCLUSIONS: Our findings suggested that FR might act as a
      chemopreventive agent with antioxidant properties offering effective protection
      against oxidative DNA damage in a concentration-dependent manner in vitro and in
      vivo.

PMID- 24089631
TI  - Oxidant-antioxidant balance in the blood of patients with chronic obstructive
      pulmonary disease after smoking cessation.
AB  - The effect of smoking cessation on the oxidative stress in patients with chronic
      obstructive pulmonary disease (COPD) was assessed. We recruited 73 smokers with
      COPD (study group), whose blood was analysed before smoking cessation, after the
      1st, 2nd, and 3rd months of abstinence, 35 healthy nonsmokers (Control I), and 35
      smokers with COPD (Control II). Blood was taken once in Control I and 4 times
      (every month) in Control II. In the study group conjugated dienes (CDs) level in
      plasma and erythrocytes before smoking cessation was 3 and 6.5 times higher than
      in Control I, respectively (P < 0.001), while thiobarbituric acid-reactive
      substances (TBARS) level was 89% (P < 0.001) and 51% higher (P < 0.01),
      respectively. Superoxide dismutase (SOD) activity was 40% higher (P < 0.05) while
      glutathione peroxidase (GPx) was 41% lower (P < 0.001) than in Control I. In
      Control II, the similar differences as compared to Control I were observed
      throughout the study. Smoking cessation resulted in decrease of CDs, TBARS, and
      SOD and GPx increase, with no changes in catalase and vitamins A and E. COPD is
      accompanied by oxidative stress. A three-month tobacco abstinence facilitated
      restoring the oxidant-antioxidant balance systemically, but it did not affect
      spirometric parameters. 

PMID- 24089628
TI  - Quinolinic acid: an endogenous neurotoxin with multiple targets.
AB  - Quinolinic acid (QUIN), a neuroactive metabolite of the kynurenine pathway, is
      normally presented in nanomolar concentrations in human brain and cerebrospinal
      fluid (CSF) and is often implicated in the pathogenesis of a variety of human
      neurological diseases. QUIN is an agonist of N-methyl-D-aspartate (NMDA)
      receptor, and it has a high in vivo potency as an excitotoxin. In fact, although
      QUIN has an uptake system, its neuronal degradation enzyme is rapidly saturated,
      and the rest of extracellular QUIN can continue stimulating the NMDA receptor.
      However, its toxicity cannot be fully explained by its activation of NMDA
      receptors it is likely that additional mechanisms may also be involved. In this
      review we describe some of the most relevant targets of QUIN neurotoxicity which
      involves presynaptic receptors, energetic dysfunction, oxidative stress,
      transcription factors, cytoskeletal disruption, behavior alterations, and cell
      death. 

PMID- 24089632
TI  - Equivalence and interchangeability of narrow therapeutic index drugs in organ
      transplantation.
AB  - The calcineurin inhibitors (CNIs), ciclosporin and tacrolimus, are the mainstay
      of immunosuppression in solid organ transplantation. Generic formulations of
      these drugs are now available. With increasing pressure on healthcare budgets and
      the consequent need to match health expectations to available resources,
      substitution with a generic product appears an attractive option to reduce costs.
      Approval of generic products differs from innovator drugs, and narrow therapeutic
      index drugs (NTIs; including CNIs) bring their own particular considerations.
      With NTIs, small variations in drug exposure could result in reduced
      immunosuppression or drug toxicity with potentially adverse effects on patient
      outcomes. NTIs are subject to stricter regulatory approval versus many other
      generic drugs. However, different generic formulations may still not necessarily
      be therapeutically equivalent in individuals, raising the possibility of
      significant differences in exposure between products. Although regional
      recommendations vary, many guidelines emphasise the need for NTI drug
      substitution to be initiated by the transplant physician, thus ensuring careful
      therapeutic monitoring and reduced negative patient impact. The need for
      therapeutic monitoring during generic substitution has important implications for
      the overall costs of generic treatment as these costs have to be factored in to
      the potential savings made from using generic formulations. The reduced
      acquisition costs of generic products may not necessarily translate into lower
      overall healthcare costs. This article examines the issue of equivalence and
      interchangeability of NTI drugs used in organ transplantation, the implications
      of the approval process for generic drugs on treatment efficacy and safety, and
      the effective management of substitutions between products.

PMID- 24089633
TI  - Molecular and Clinical Characterization of Giardia duodenalis Infection in
      Preschool Children from Lisbon, Portugal.
AB  - Giardia duodenalis is the most prevalent intestinal protozoan infection
      especially in children. In Portugal scarce data are available relative to this
      infection in preschoolers. The present study was conducted from April to July
      2009 in public preschools in Lisbon enrolling 316 children. Stool examination was
      performed through microscopy. Molecular analysis was conducted in all positive
      samples for G. duodenalis in order to determine the assemblage and subassemblage
      of this parasite. Eight of the preschoolers studied children (2.5%, 8/316) were
      infected with G. duodenalis. Additionally the brother of one of the infected
      children was also infected. Genotyping analysis targeting ssu-rRNA and beta 
      giardin loci revealed six infections with assemblage A and 3 with assemblage B.
      Sub-assemblage determination was possible in four of the samples, with three A2
      and one A3. The limited number of cases precluded an association of a determined
      symptom with an assemblage. The data presented here show the relevance of
      considering G. duodenalis analysis in children with intestinal complaints even in
      developed countries. 

PMID- 24089634
TI  - Total 4EBP1 Is Elevated in Liver of Rats in Response to Low Sulfur Amino Acid
      Intake.
AB  - Translation initiation is known to be regulated by the binding of eukaryotic
      initiation factor 4E (eIF4E) by binding proteins (4EBPs), and there is evidence
      that amino acid deprivation and other cellular stresses upregulate 4EBP1
      expression. To pursue the question of whether diets limited in an essential amino
      acid lead to induction of 4EBP1 expression in vivo, diets that varied in
      methionine and cystine content were fed to rats for 7 days, and 4EBP1 mRNA and
      protein levels and 4EBP1 phosphorylation state were determined. Total 4EBP1 mRNA
      and protein abundance increased in liver of rats with severely deficient intakes
      of sulfur amino acids (0.23% or 0.11% methionine without cystine) but not in
      animals with a less restricted intake of sulfur amino acids (0.11% methionine
      plus 0.35% cystine) but a similarly restricted intake of total diet (53 to 62% of
      control). The amount of 4EBP1 binding activity ( alpha + beta forms) was elevated
      in liver of rats fed sulfur amino acid-deficient diets, whereas the
      hyperphosphorylation of 4EBP1 was not affected by dietary treatment. Results
      suggest that changes in total 4EBP1 expression should be considered when
      examining mechanisms that attenuate protein synthesis during amino acid
      deficiency states. 

PMID- 24089635
TI  - Cancer, Health Literacy, and Happiness: Perspectives from Patients under
      Chemotherapy.
AB  - Cancer is a dreaded disease that affects all dimensions of human life. In this
      context, issues related to the quality of life-as happiness, perception about
      health status, or health literacy-are important. This study aims to analyze the
      following topics the perception: the Portuguese cancer patients have about their
      health status while undergoing chemotherapy, the satisfaction with the
      information relating to their health, their level of happiness, and their vision
      of the future. An observational, cross-sectional, and descriptive study was
      developed. Data were collected between May and July 2012 in the day hospital of a
      central hospital in northern Portugal. The sample was composed of 92 cancer
      patients who were asked to answer a questionnaire during chemotherapy. The
      results indicate that, despite this life-threatening disease, patients consider
      themselves fairly happy and have an optimistic view of the future. Information
      about their health condition and religious beliefs was important coping
      mechanisms to help dealing with the suffering caused by the disease. The study
      highlights the importance of providing care in a holistic way. Nurses must be
      alert and available to listen, answer questions, provide supporting structures,
      or refer to other professionals when needed. 

PMID- 24089636
TI  - Postnatal depression is a public health nursing issue: perspectives from norway
      and ireland.
AB  - The framework provided by the Millennium Development Goals includes maternal
      health as an area of priority. Postnatal depression (PND) is a serious public
      health issue because it occurs at a crucial time in a mothers' life, can persist
      for long periods, and can have adverse effects on partners and the emotional,
      behavioural, and cognitive development of infants and children. Internationally,
      public health nurses (PHNs) are key professionals in the delivery of health care
      to mothers in the postpartum period, and international research collaborations
      are encouraged. Two researchers from the European Academy of Nursing Science
      (EANS) identified a need to collaborate and strengthen research capacity and
      discussion on postnatal depression, a public health nursing issue in both
      countries. Within the context of public health and public health nursing in
      Ireland and Norway, the aim of this paper is to present a discussion on the
      concept of PND, prevalence, and outcomes; screening issues for PHNs; and the
      research evidence of the benefits of social support in facilitating recovery for
      new mothers. 

PMID- 24089637
TI  - The engagement in physical activity for middle-aged and older adults with
      multiple chronic conditions: findings from a community health assessment.
AB  - The current aging trends accompanying the increasing prevalence of multiple
      chronic conditions (MCCs) and decreasing participation in physical activity (PA)
      have swept the United States. In light of the magnitude of this phenomenon, this
      study seeks to identify the most common MCC combinations and their relationships
      with PA level. A cross-sectional study, Brazos Valley Health Assessment, was
      conducted between October 2009 and July 2010. All data analyses were performed by
      STATA 12.0. The overall sample which met the inclusion criteria is 2,603. Among
      people older than 45 years, chronic conditions of cardiovascular, endocrine, and
      musculoskeletal systems were the most prevalent. Participants with three chronic
      conditions were less likely to meet the PA standard than those with only two
      chronic conditions. Younger age, women, rural residence, and unsafe environments
      were related to the lower PA level. After adjusting for seven covariates, all
      MCCs combinations adversely affect the level of PA (OR < 1.0, P < 0.05). People
      with MCCs were among the least active subgroups despite the health benefits of
      doing exercise. Given the well-documented benefits of physical activity for
      delaying the onset or progression of MCCs, public health efforts to enhance
      regular PA in middle-aged and older adults are recommended. 

PMID- 24089638
TI  - Differential item functioning related to age in the reading subtest of the test
      of functional health literacy in adults.
AB  - Differential item functioning (DIF) occurs when items in a measure perform in
      ways that are different for members of a target group when the different
      performance is not related to the individual's overall ability to be assessed.
      DIF may arise for a number of reasons but is often evaluated in order to ensure
      that tests and measures are fair evaluations of a group's abilities. Based on
      observations when administering the test, we developed the hypothesis that some
      items on the reading comprehension subtest of the Test of Functional Health
      Literacy (TOFHLA) might be differentially more difficult for older adults and the
      elderly due to its use of the cloze response format, in which the participant is
      required to determine what word, when placed in a blank space in a sentence, will
      ensure that the sentence is intelligible. Others have suggested that the cloze
      response format may make demands on verbal fluency, an ability that is reduced
      with the increasing age. Our analyses show that age-related DIF may present in a
      nearly one-half of reading comprehension items of the TOFHLA. Results of this
      measure in older persons should be interpreted cautiously. 

PMID- 24089639
TI  - A Quantitative Structure-Activity Relationship and Molecular Modeling Study on a
      Series of Heteroaryl- and Heterocyclyl-Substituted Imidazo[1,2-a]Pyridine
      Derivatives Acting as Acid Pump Antagonists.
AB  - A quantitative structure-activity relationship (QSAR) and molecular docking study
      has been performed on a series of heteroaryl- and heterocyclyl-substituted
      imidazo[1,2-a]pyridine derivatives acting as acid pump antagonists in order to
      have a better understanding of the mechanism of H(+)/K(+)-ATPase inhibition. The
      QSAR study shows a significant correlation of activity with Global Topological
      Charge Indices (GTCI) of the compounds and the hydrophobic constant pi of some
      substituents, indicating that the charge transfer within the molecule and the
      hydrophobic property of some substituents will be the controlling factor of the
      activity of these compounds and that there can be dispersion interaction between
      the molecules and the receptor, where some substituents may have hydrophobic
      interaction, too. Based on this correlation some new compounds with higher
      potency have been predicted and their docking study has been performed to see if
      they can have better interaction with the receptor. The ADME properties of these
      predicted compounds have also been reported that follow Lipinski's rule of five. 

PMID- 24089640
TI  - Cost-effectiveness of catheter ablation for rhythm control of atrial
      fibrillation.
AB  - Objective. The objective of this study is to evaluate the cost-effectiveness of
      catheter ablation for rhythm control compared to antiarrhythmic drug (AAD)
      therapy in patients with atrial fibrillation (AF) who have previously failed on
      an AAD. Methods. An economic model was developed to compare (1) catheter ablation
      and (2) AAD (amiodarone 200 mg/day). At the end of the initial 12 month phase of
      the model, patients are classified as being in normal sinus rhythm or with AF,
      based on data from a meta-analysis. In the 5-year Markov phase of the model,
      patients are at risk of ischemic stroke each 3-month model cycle. Results. The
      model estimated that, compared to the AAD strategy, ablation had $8,539 higher
      costs, 0.033 fewer strokes, and 0.144 more QALYS over the 5-year time horizon.
      The incremental cost per QALY of ablation compared to AAD was estimated to be
      $59,194. The probability of ablation being cost-effective for willingness to pay
      thresholds of $50,000 and $100,000 was estimated to be 0.89 and 0.90,
      respectively. Conclusion. Based on current evidence, pulmonary vein ablation for
      treatment of AF is cost-effective if decision makers willingness to pay for a
      QALY is $59,194 or higher. 

PMID- 24089641
TI  - N-Phenylpropyl-N'-(3-methoxyphenethyl)piperazine (YZ-185) Attenuates the
      Conditioned-Rewarding Properties of Cocaine in Mice.
AB  - Sigma receptor antagonists diminish the effects of cocaine in behavioral assays,
      including conditioned place preference. Previous locomotor activity experiments
      in mice determined that the sigma receptor ligand YZ-185 (N-phenylpropyl-N'-(3
      methoxyphenethyl)piperazine) enhanced cocaine-induced hyperactivity at a lower
      (0.1  MU mol/kg) dose and dose-dependently attenuated cocaine-induced
      hyperactivity at higher (3.16-31.6  MU mol/kg) doses. The present study
      investigated the effect of YZ-185 on cocaine's conditioned-rewarding properties
      in mice. YZ-185 (0.1, 0.316, 3.16, and 31.6  MU mol/kg) did not have intrinsic
      activity to produce conditioned place preference or aversion. A higher (31.6  MU
      mol/kg) YZ-185 dose, but not lower (0.1-3.16  MU mol/kg) YZ-185 doses, prevented
      the development of place preference to cocaine (66  MU mol/kg). YZ-185 did not
      alter the expression of cocaine place preference. To further characterize YZ
      185's behavioral profile, its effects in the elevated zero maze and rotarod
      procedures were also determined; YZ-185 produced no significant change from
      baseline in either assay, indicating that the sigma receptors probed by YZ-185 do
      not regulate anxiety-like or coordinated motor skill behaviors. Overall, these
      results suggest that YZ-185 is a sigma receptor antagonist at the 31.6  MU mol/kg
      dose and demonstrate that sigma receptors can mediate the development of the
      conditioned-rewarding properties of cocaine. 

PMID- 24089644
TI  - Reliability and validity of the persian version of the fatigue severity scale in
      idiopathic Parkinson's disease patients.
AB  - As one of the most frequent symptoms, measurement of fatigue is an issue of
      interest in Parkinson's disease (PD). The fatigue severity scale (FSS) is one of
      the recommended questionnaires for this purpose. The aim of our study was to
      evaluate psychometric properties of the Persian version of the FSS (FSS-Per) to
      assess fatigue in PD patients. Ninety nondemented idiopathic Parkinson's disease
      (IPD) patients were consecutively recruited from an outpatient referral movement
      disorder clinic. In addition to the disease severity scales, the FSS-Per was used
      for fatigue measurement. The internal consistency coefficient was larger than 0.8
      for all of the items with a total Cronbach's alpha of 0.96 (95% CI: 0.95-0.97).
      The FSS-Per score correlated with the UPDRS score (r = 0.55, P < 0.001) and the
      "Hoehn and Yahr" (HY) stage (r = 0.48, P < 0.001). The total score of the FSS-Per
      significantly discriminated IPD patients with more severe disability (HY stage >
      2) versus those with less severe disease (HY stage <=2) (AUC = 0.81 (95% CI: 0.72
      0.90)). The FSS-Per fulfilled a high internal consistency and construct validity
      to measure the severity of fatigue in Iranian IPD patients. These acceptable
      psychometric properties were reproducible in subgroups of IPD patients regarding
      different levels of education, disease severity, sex and age groups. 

PMID- 24089643
TI  - Effects of vitamin e on bone biomechanical and histomorphometric parameters in
      ovariectomized rats.
AB  - The present study examined the dose-dependent effect of vitamin E in reversing
      bone loss in ovariectomized (Ovx) rats. Sprague-Dawley rats were either Sham
      operated (Sham) or Ovx and fed control diet for 120 days to lose bone.
      Subsequently, rats were divided into 5 groups (n = 12/group): Sham, Ovx-control,
      low dose (Ovx + 300 mg/kg diet; LD), medium dose (Ovx + 525 mg/kg diet; MD), and
      high dose (Ovx + 750 mg/kg diet; HD) of vitamin E and sacrificed after 100 days.
      Animals receiving MD and HD of vitamin E had increased serum alkaline phosphatase
      compared to the Ovx-control group. Bone histomorphometry analysis indicated a
      decrease in bone resorption as well as increased bone formation and
      mineralization in the Ovx groups supplemented with MD and HD of vitamin E.
      Microcomputed tomography findings indicated no effects of vitamin E on trabecular
      bone of fifth lumbar vertebrae. Animals receiving HD of vitamin E had enhanced
      fourth lumbar vertebra quality as evidenced by improved ultimate and yield load
      and stress when compared to Ovx-control group. These findings demonstrate that
      vitamin E improves bone quality, attenuates bone resorption, and enhances the
      rate of bone formation while being unable to restore bone density and trabecular
      bone structure. 

PMID- 24089642
TI  - Microglia control neuronal network excitability via BDNF signalling.
AB  - Microglia-neuron interactions play a crucial role in several neurological
      disorders characterized by altered neural network excitability, such as epilepsy
      and neuropathic pain. While a series of potential messengers have been postulated
      as substrates of the communication between microglia and neurons, including
      cytokines, purines, prostaglandins, and nitric oxide, the specific links between
      messengers, microglia, neuronal networks, and diseases have remained elusive.
      Brain-derived neurotrophic factor (BDNF) released by microglia emerges as an
      exception in this riddle. Here, we review the current knowledge on the role
      played by microglial BDNF in controlling neuronal excitability by causing
      disinhibition. The efforts made by different laboratories during the last decade
      have collectively provided a robust mechanistic paradigm which elucidates the
      mechanisms involved in the synthesis and release of BDNF from microglia, the
      downstream TrkB-mediated signals in neurons, and the biophysical mechanism by
      which disinhibition occurs, via the downregulation of the K+-Cl- cotransporter
      KCC2, dysrupting Cl- homeostasis, and hence the strength of GABA(A)- and glycine
      receptor-mediated inhibition. The resulting altered network activity appears to
      explain several features of the associated pathologies. Targeting the molecular
      players involved in this canonical signaling pathway may lead to novel
      therapeutic approach for ameliorating a wide array of neural dysfunctions.

PMID- 24089645
TI  - Quality of red blood cells isolated from umbilical cord blood stored at room
      temperature.
AB  - Red blood cells (RBCs) from cord blood contain fetal hemoglobin that is
      predominant in newborns and, therefore, may be more appropriate for neonatal
      transfusions than currently transfused adult RBCs. Post-collection, cord blood
      can be stored at room temperature for several days before it is processed for
      stem cells isolation, with little known about how these conditions affect
      currently discarded RBCs. The present study examined the effect of the duration
      cord blood spent at room temperature and other cord blood characteristics on cord
      RBC quality. RBCs were tested immediately after their isolation from cord blood
      using a broad panel of quality assays. No significant decrease in cord RBC
      quality was observed during the first 65 hours of storage at room temperature.
      The ratio of cord blood to anticoagulant was associated with RBC quality and
      needs to be optimized in future. This knowledge will assist in future development
      of cord RBC transfusion product. 

PMID- 24089647
TI  - Using basic ethical principles to evaluate safety efforts in transfusion
      medicine.
AB  - Pursuit of pharmaceutical purity of the blood in the bag has led to a shrinking
      donor base and a significantly more expensive product. Decisions regarding new
      infectious marker testing and donor deferrals have typically been made
      emphasizing decreasing one specific risk without considering the effect the
      intervention will have on the overall safety and availability of blood
      transfusion. Regulations have been formulated by governmental agencies with
      limited input from the medical community. The decision making process has lacked
      risk benefit analyses and has not had the robustness associated with spirited
      discussions. Policies made in this manner may result in certain risks being
      decreased but can also have adverse unintended consequences. Being guided by the
      ethical principles of nonmaleficence, beneficence, autonomy, and justice, we need
      to evaluate our actions in the context of overall blood safety rather than
      narrowly focusing on any one area. 

PMID- 24089648
TI  - Comparative efficacy of three forms of parenteral iron.
AB  - Intravenous iron therapy is a useful treatment for the rapid correction of iron
      deficiency anaemia and can be used to avoid or reduce the requirement for
      allogeneic blood transfusion. Several intravenous iron preparations are available
      commercially which differ in cost, mode of administration and side effect
      profile. There are few data directly comparing the efficacy of these
      preparations. In this retrospective single-centre study, we present the results
      from two hundred and eight patients treated using three different iron
      preparations (iron dextran, iron sucrose and ferric carboxymaltose) and compare
      the effect on haemoglobin levels and other measures of iron deficiency six weeks
      after treatment. Within the limitations of our study design, we show a
      statistically and clinically significant difference in efficacy between these
      preparations. 

PMID- 24089646
TI  - State of the art in stem cell research: human embryonic stem cells, induced
      pluripotent stem cells, and transdifferentiation.
AB  - Stem cells divide by asymmetric division and display different degrees of
      potency, or ability to differentiate into various specialized cell types. Owing
      to their unique regenerative capacity, stem cells have generated great enthusiasm
      worldwide and represent an invaluable tool with unprecedented potential for
      biomedical research and therapeutic applications. Stem cells play a central role
      in the understanding of molecular mechanisms regulating tissue development and
      regeneration in normal and pathological conditions and open large possibilities
      for the discovery of innovative pharmaceuticals to treat the most devastating
      diseases of our time. Not least, their intrinsic characteristics allow the
      engineering of functional tissues for replacement therapies that promise to
      revolutionize the medical practice in the near future. In this paper, the authors
      present the characteristics of pluripotent stem cells and new developments of
      transdifferentiation technologies and explore some of the biomedical applications
      that this emerging technology is expected to empower. 

PMID- 24089649
TI  - Potential uses of cord blood in cardiac surgery.
AB  - Despite advances in the fields of prevention, medical intervention and surgical
      therapy, cardiovascular disease remains a major public healthcare issue. A
      promising area of research is the potential application of regenerative therapies
      with pluripotential stem cells to reduce the burden of heart disease and its
      sequelae. Umbilical cord blood, a rich source of multiple populations of
      nonembryonic stem cells, will be a valuable resource and has the potential to
      advance therapeutic options for patients with acquired and congenital heart
      disease. 

PMID- 24089650
TI  - Ethical aspects of blood donors and the recipients of their blood.
AB  - To date medical care is inextricable based on blood donors and blood products.
      The continuing increase and intensification of tests and guidelines also results
      in a change in deferral and abnormal test results. Donors and recipients of their
      blood are faced with this information and are confronted with a kaleidoscope of
      thoughts and emotions. The discussion with respect to paid versus nonpaid
      donation is not new, but other aspects are less often discussed. We describe
      these other aspects for donors and recipients of their blood and hope to open the
      ethical discussion; if and to what extent we should have limits? 

PMID- 24089651
TI  - Questionnaire-related deferrals in regular blood donors in norway.
AB  - Voluntary donation is a key issue in transfusion medicine. To ensure the safety
      of blood transfusions, careful donor selection is important. Although new
      approaches to blood safety have dramatically reduced the risks for infectious
      contamination of blood components, the quality and the availability of blood
      components depend on the willingness to donate and the reliability of the
      information given by the donors about their own health, including risk behavior.
      As donors who are deferred by the blood bank will be less motivated to return for
      donation, it is important to reduce the number of deferrals. The aims of the
      present study were to investigate the reasons for deferral of registered donors
      coming to the blood bank for donation, in order to identify areas of importance
      for donor education-as these deferrals potentially could be avoided by better
      donor comprehension. Deferral related to testing of donors is not included in
      this study as these deferrals are dependent on laboratory results and cannot be
      indentified by questionnaire or interview. Data were collected from all blood
      donors in a period for 18 months who came for blood donation at a large
      university hospital in Norway. 1 163 of the 29 787 regular donors, who showed up
      for donation, were deferred (3.9%). The main reasons were intercurrent illness (n
      = 182) (15.6%), skin ulcers (n = 170) (14.6%), and risk behaviour (n = 127)
      (10.9%). In a community, intercurrent illnesses, skin ulcers, and potential risk
      behavior are the most frequent reasons for deferral of regular donors.
      Strategized effort on donor education is needed, as "failure to donate" reduces
      donor motivation. 

PMID- 24089652
TI  - Epidemiological Profiles of Foreign-Born and US-Born Hispanic Blood Donors in a
      Major Metropolitan Area in the United States.
AB  - Background. The explosive growth of Hispanics in the US makes this population a
      significant and untapped source for blood donation. Methods. A cross-sectional
      study was performed to evaluate blood donation behaviors and demographics of
      foreign-born and US-born Hispanic donors between 2006 and 2009 in metropolitan
      Atlanta, GA, USA. Bivariate analyses and multivariate logistic regression were
      used to assess factors associated with foreign-born donors. Results. 5,119
      foreign-born and 11,841 US-born Hispanics donated blood. Foreign-born Hispanic
      donors were more likely than US-born donors to be blood group O (57.6% versus
      52.0%; P < .001) and more frequent donors (2.2 versus 2.0; P < .001). Cuban-born
      donors had the highest rates of return donation (63.2%). In contrast, Mexicans,
      the most prevalent subpopulation among foreign-born Hispanic donors (31.8%), had
      the lowest rates of return donation (42.0%). Conclusions. The heterogeneity found
      among Hispanic donors in this study is valuable for the design of recruitment
      strategies to increase blood donations. 

PMID- 24089653
TI  - A comparison study of the blood component quality of whole blood held overnight
      at 4 degrees c or room temperature.
AB  - Background. The use of plasma frozen within 24 hrs is likely to increase. Whole
      blood (WB) and buffy coats (BCs) can be held for a few hrs or overnight before
      processing. Methods. Twenty-four bags of WB for plasma and 12 bags for platelet
      (PLT) concentrates were collected. The fresh frozen plasma (FFP) was prepared
      within 6 hrs. I-FP24 and II-FP24 samples were prepared either from leukodepleted
      WB that was held overnight or from WB that was held overnight before
      leukodepletion. The PLT concentrates (PCs) were prepared from BCs within 6 hrs
      (PC1) and within 18 to 24 hrs (PC2). The typical coagulation factors and some
      biochemical parameters were determined. Results. Compared to the FFP samples, the
      levels of FVII and FVIII in the I-FP24 and II-FP24 samples decreased
      significantly. The pH, Na(+), LDH, and FHb levels differed significantly between
      II-FP24 and FFP. Compared to PC1, PC2 exhibited lower pH, pO2, and Na(+) levels,
      a higher PLT count, and increased pCO2, K(+), Lac, and CD62P expression levels.
      Conclusion. FP24 is best prepared from WB that was stored overnight at 4 degrees
      C and then leukodepleted and separated within 24 hrs. PCs are best produced from
      BCs derived from WB that was held overnight at room temperature. 

PMID- 24089654
TI  - Comprehensive Look at Blood Transfusion Utilization in Total Joint Arthroplasty
      at a Single Academic Medical Center under a Single Surgeon.
AB  - The utilization of autologous and allogeneic transfusions in total joint
      arthroplasties was to characterize patients who may benefit from giving
      preoperative blood donations. We conducted a retrospective chart review of 525
      patients to document preoperative hematocrit, estimated blood loss, length of
      stay, transfusions, and medical comorbidities. Results of our review showed that
      total hip arthroplasty revision (THA-R) had the highest prevalence of
      transfusions (60%) followed by total hip arthroplasty (THA, 53%), total knee
      arthroplasty-revision (TKA-R, 33%), and total knee arthroplasty (TKA, 23%). There
      was significant waste of autologous donations: 92% of TKA patients, 64% of THA,
      and 33% of THA-R patients wasted on average 1.527, 1.321, and 1.5 autologous
      units, respectively. Pre-operative hematocrit was the strongest predictor of
      future transfusion need across all procedures, and primary THA had additional
      predictors in age and gender. 

PMID- 24089655
TI  - Awareness and Acceptable Practices: IRB and Researcher Reflections on the
      Havasupai Lawsuit.
AB  - BACKGROUND: In 2003, Havasupai tribe members in Arizona discovered that their DNA
      samples, collected for genetic studies on Type II diabetes, had been used for
      studies on schizophrenia, migration, and inbreeding without their approval. The
      resulting lawsuit brought by the Havasupai reached a settlement in April 2010 in
      which tribe members received monetary compensation and the return of DNA samples.
      In this study, we examine the perceptions of Institutional Review Board (IRB)
      chairpersons and human genetic researchers about the case and its impact on the
      practice of research. METHODS: Twenty-minute semi-structured interviews were
      conducted with 26 Institutional Review Board (IRB) chairs and researchers at six
      top NIH-funded institutions. Participants were questioned about their knowledge
      and perceived impact of the Havasupai case and their perceptions of informed
      consent in genetic research studies. RESULTS: We found that most study
      participants did not perceive that the Havasupai case had a large impact.
      However, we identified key concerns and opinions of the case, in particular,
      increased awareness of culturally sensitive issues with informed consent and
      secondary uses of samples. CONCLUSIONS: The results provide a deeper
      understanding of how informed consent issues are understood by IRB members and
      human genetic researchers and the implications for research ethics education.

PMID- 24089656
TI  - A Study of Zoledronic Acid as Neo-Adjuvant, Perioperative Therapy in Patients
      with Resectable Pancreatic Ductal Adenocarcinoma.
AB  - BACKGROUND: Pancreatic ductal adenocarcinoma (PDAC) is an aggressive malignancy
      characterized by abundant granulocytic myeloid-derived suppressor cells (G-MDSC =
      CD45+/Lin-/CD33+/CD11b+/CD15+), which infiltrate tumors and suppress anti-tumor
      immunity. We have previously demonstrated in a murine model of PDAC that
      zoledronic acid (ZA) depletes G-MDSC resulting in decreased tumor growth and
      improved survival. We report here the results of a phase 1 clinical trial
      (NCT00892242) using ZA as neo-adjuvant, perioperative therapy in patients with
      non-metastatic, resectable pancreatic adenocarcinoma. METHODS: Eligible PDAC
      patients received ZA (4mg) IV 2 weeks prior to surgery. Patients then received 2
      additional doses of ZA 4 weeks apart. Blood and bone marrow were obtained from
      patients prior to treatment with ZA and 3 months after surgery for analysis of G
      MDSC by flow cytometry. RESULTS: Twenty-three patients received pre-operative ZA
      with at least 6 months of follow-up Only 15 PDAC patients had non-metastatic
      PDAC, which was amenable to resection. ZA was well tolerated, and all adverse
      events were grade 1 or 2. The most common adverse events were fatigue, abdominal
      pain/discomfort, anorexia, and arthralgia. Of resected PDAC patients treated with
      ZA, 1- and 2-year overall survival (OS) was 85.7% and 33.3%, respectively, with a
      median OS of 18 months. This group had a 1- and 2-year progression-free survival
      (PFS) of 26.9% and 8.9%, respectively, with a median PFS of 12 months. The
      prevalence of G-MDSC was unchanged in the blood and bone marrow of PDAC patients
      pre- and post-treatment with ZA. CONCLUSION: ZA is safe and well tolerated as neo
      adjuvant, peri-operative therapy in PDAC patients. In this small study, we did
      not observe a difference in OS or PFS compared to historical controls. Also,
      there was no difference in the prevalence of G-MDSC in the blood and bone marrow
      of PDAC patients pre- and post-treatment with ZA.

PMID- 24089658
TI  - Beliefs Underlying the Decision to Eat Breakfast: The Role of Theory-based
      Behavioral Analysis in the Development of Policy, Communication and Educational
      Interventions for Healthy Eating.
AB  - Policy, communication, and education efforts to influence any social or health
      outcome are more effective if based on an understanding of the underlying
      behaviors and their determinants. This conceptual paper outlines how behavioral
      theory can help design interventions for one healthy eating behavior, eating
      breakfast. More specifically, the paper illustrates how a prominent health
      behavior theory, the Reasoned Action Approach, can be used to guide formative
      research to identify factors underlying people's decisions. Select findings are
      presented from three studies of beliefs underlying eating breakfast: online
      surveys with 1185 undergraduates from a large university in Indiana; in-depth
      interviews with 61 adults from four Indiana worksites; and 63 in-depth interviews
      with students from three middle schools in rural Indiana. Analyses of data from
      the undergraduates demonstrated the role of self-efficacy. Analyses of data from
      the working adults revealed the importance of normative beliefs about what
      employers believed. Analyses comparing consequences perceived by adults with
      those perceived by middle school students found that both groups believed that
      eating breakfast would provide energy but only middle school students believed
      that eating breakfast would improve alertness. For each finding, the theory is
      presented, the finding is described, implications for interventions are
      suggested, and the need for additional research is outlined. In sum, theory-based
      behavioral research can help develop interventions at intrapersonal,
      interpersonal, and environmental levels that are warranted to encourage healthy
      eating.

PMID- 24089657
TI  - Natural killer T cell based Immunotherapy.
AB  - Natural killer T (NKT) cells play an important immunoregulatory role and are
      thought to bridge the innate and adaptive immune responses. Following activation
      through cognate interactions with lipid antigen presented in the context of CD1d
      molecules, NKT cells rapidly produce a plethora of cytokines and can also mediate
      cytotoxicity. Due to their potent effector functions, extensive research has been
      performed to increase our understanding on how to effectively modulate these
      cells. In fact, NKT cell agonists have been used as vaccine adjuvants to enhance
      antigen specific T and B cell responses to infections and malignancy. In this
      review, we will focus on recent advances in NKT cell-based vaccination
      strategies. Given the role that NKT cells play in autoimmune disease, infectious
      diseases, cancer, transplant immunology and dermatology, it is important to
      understand how to effectively guide their effector functions in order to develop
      novel immunotherapeutic strategies.

PMID- 24089659
TI  - MicroRNAs in kidney fibrosis and diabetic nephropathy: roles on EMT and EndMT.
AB  - MicroRNAs (miRNAs) are a family of small, noncoding RNAs that regulate gene
      expression in diverse biological and pathological processes, including cell
      proliferation, differentiation, apoptosis, and carcinogenesis. As a result,
      miRNAs emerged as major area of biomedical research with relevance to kidney
      fibrosis. Fibrosis is characterized by the excess deposition of extracellular
      matrix (ECM) components, which is the end result of an imbalance of metabolism of
      the ECM molecule. Recent evidence suggests that miRNAs participate in the
      fibrotic process in a number of organs including the heart, kidney, liver, and
      lung. Epithelial mesenchymal transition (EMT) and endothelial mesenchymal
      transition (EndMT) programs play vital roles in the development of fibrosis in
      the kidney. A growing number of the extracellular and intracellular molecules
      that control EMT and EndMT have been identified and could be exploited in
      developing therapeutics for fibrosis. This review highlights recent advances on
      the role of miRNAs in the kidney diseases; diabetic nephropathy especially
      focused on EMT and EndMT program responsible for the development of kidney
      fibrosis. These miRNAs can be utilized as a potential novel drug target for the
      studying of underlying mechanism and treatment of kidney fibrosis. 

PMID- 24089660
TI  - Materials and manufacturing technologies available for production of a pediatric
      bioabsorbable stent.
AB  - Transcatheter treatment of children with congenital heart disease such as
      coarctation of the aorta and pulmonary artery stenosis currently involves the use
      of metal stents. While these provide good short term results, there are long term
      complications with their use. Children outgrow metal stents, obligating them to
      future transcatheter dilations and eventual surgical removal. A bioabsorbable
      stent, or a stent that goes away with time, would solve this problem.
      Bioabsorbable stents are being developed for use in coronary arteries, however
      these are too small for use in pediatric congenital heart disease. A
      bioabsorbable stent for use in pediatric congenital heart disease needs to be low
      profile, expandable to a diameter 8 mm, provide sufficient radial strength, and
      absorb quickly enough to allow vessel growth. Development of absorbable coronary
      stents has led to a great understanding of the available production techniques
      and materials such as bioabsorbable polymers and biocorrodable metals. Children
      with congenital heart disease will hopefully soon benefit from the current
      generation of bioabsorbable and biocorrodable materials and devices. 

PMID- 24089661
TI  - Evolutionary relations of Hexanchiformes deep-sea sharks elucidated by whole
      mitochondrial genome sequences.
AB  - Hexanchiformes is regarded as a monophyletic taxon, but the morphological and
      genetic relationships between the five extant species within the order are still
      uncertain. In this study, we determined the whole mitochondrial DNA (mtDNA)
      sequences of seven sharks including representatives of the five Hexanchiformes,
      one squaliform, and one carcharhiniform and inferred the phylogenetic
      relationships among those species and 12 other Chondrichthyes (cartilaginous
      fishes) species for which the complete mitogenome is available. The monophyly of
      Hexanchiformes and its close relation with all other Squaliformes sharks were
      strongly supported by likelihood and Bayesian phylogenetic analysis of 13,749
      aligned nucleotides of 13 protein coding genes and two rRNA genes that were
      derived from the whole mDNA sequences of the 19 species. The phylogeny suggested
      that Hexanchiformes is in the superorder Squalomorphi, Chlamydoselachus anguineus
      (frilled shark) is the sister species to all other Hexanchiformes, and the
      relations within Hexanchiformes are well resolved as Chlamydoselachus,
      (Notorynchus, (Heptranchias, (Hexanchus griseus, H. nakamurai))). Based on our
      phylogeny, we discussed evolutionary scenarios of the jaw suspension mechanism
      and gill slit numbers that are significant features in the sharks. 

PMID- 24089662
TI  - An assessment of hazards caused by electromagnetic interaction on humans present
      near short-wave physiotherapeutic devices of various types including hazards for
      users of electronic active implantable medical devices (AIMD).
AB  - Leakage of electromagnetic fields (EMF) from short-wave radiofrequency
      physiotherapeutic diathermies (SWDs) may cause health and safety hazards
      affecting unintentionally exposed workers (W) or general public (GP) members
      (assisting patient exposed during treatment or presenting there for other
      reasons). Increasing use of electronic active implantable medical devices
      (AIMDs), by patients, attendants, and workers, needs attention because
      dysfunctions of these devices may be caused by electromagnetic interactions. EMF
      emitted by 12 SWDs (with capacitive or inductive applicators) were assessed
      following international guidelines on protection against EMF exposure
      (International Commission on Nonionizing Radiation Protection for GP and W, new
      European directive 2013/35/EU for W, European Recommendation for GP, and European
      Standard EN 50527-1 for AIMD users). Direct EMF hazards for humans near inductive
      applicators were identified at a distance not exceeding 45 cm for W or 62 cm for
      GP, but for AIMD users up to 90 cm (twice longer than that for W and 50% longer
      than that for GP because EMF is pulsed modulated). Near capacitive applicators
      emitting continuous wave, the corresponding distances were: 120 cm for W or 150
      cm for both-GP or AIMD users. This assessment does not cover patients who undergo
      SWD treatment (but it is usually recommended for AIMD users to be careful with
      EMF treatment). 

PMID- 24089663
TI  - The ALADINO study: a national study of prevalence of overweight and obesity in
      Spanish children in 2011.
AB  - The aim of the study was to determine the prevalence of overweight and obesity in
      children in Spain using different sets of cut-off criteria, through a community
      based cross-sectional study. The study was conducted in a representative sample
      of Spanish children between 6 and 9 years, recruited in Spanish schools, between
      October 2010 and May 2011. 7,569 boys and girls were selected. All were weighed
      and measured, and their parents were asked about their socioeconomic background,
      food habits and physical activity. The BMI of each was calculated, and the
      prevalence of overweight and obesity was determined by age and sex using Spanish
      reference tables (SPART), IOTF reference values, and WHO growth standards. The
      prevalence of overweight in boys ranged from 14.1% to 26.7%, and in girls from
      13.8% to 25.7%, depending on the cut-off criteria. The prevalence of obesity in
      boys ranged from 11.0% to 20.9%, and in girls from 11.2% to 15.5%. The prevalence
      of obesity was the highest among those same children when using the SPART or WHO
      criteria. Overweight and obesity remain widespreading among Spanish children; a
      consensus on the definition of overweight and obesity cut-off criteria is
      necessary. 

PMID- 24089664
TI  - Respiratory management in the patient with spinal cord injury.
AB  - Spinal cord injuries (SCIs) often lead to impairment of the respiratory system
      and, consequently, restrictive respiratory changes. Paresis or paralysis of the
      respiratory muscles can lead to respiratory insufficiency, which is dependent on
      the level and completeness of the injury. Respiratory complications include
      hypoventilation, a reduction in surfactant production, mucus plugging,
      atelectasis, and pneumonia. Vital capacity (VC) is an indicator of overall
      pulmonary function; patients with severely impaired VC may require assisted
      ventilation. It is best to proceed with intubation under controlled circumstances
      rather than waiting until the condition becomes an emergency. Mechanical
      ventilation can adversely affect the structure and function of the diaphragm.
      Early tracheostomy following short orotracheal intubation is probably beneficial
      in selected patients. Weaning should start as soon as possible, and the best
      modality is progressive ventilator-free breathing (PVFB). Appropriate candidates
      can sometimes be freed from mechanical ventilation by electrical stimulation.
      Respiratory muscle training regimens may improve patients' inspiratory function
      following a SCI. 

PMID- 24089665
TI  - Computational analysis of the soluble form of the intracellular chloride ion
      channel protein CLIC1.
AB  - The chloride intracellular channel (CLIC) family of proteins has the remarkable
      property of maintaining both a soluble form and an integral membrane form acting
      as an ion channel. The soluble form is structurally related to the glutathione-S
      transferase family, and CLIC can covalently bind glutathione via an active site
      cysteine. We report approximately 0.6 MUs of molecular dynamics simulations,
      encompassing the three possible ligand-bound states of CLIC1, using the structure
      of GSH-bound human CLIC1. Noncovalently bound GSH was rapidly released from the
      protein, whereas the covalently ligand-bound protein remained close to the
      starting structure over 0.25 MUs of simulation. In the unliganded state,
      conformational changes in the vicinity of the glutathione-binding site resulted
      in reduced reactivity of the active site thiol. Elastic network analysis
      indicated that the changes in the unliganded state are intrinsic to the protein
      architecture and likely represent functional transitions. Overall, our results
      are consistent with a model of CLIC function in which covalent binding of
      glutathione does not occur spontaneously but requires interaction with another
      protein to stabilise the GSH binding site and/or transfer of the ligand. The
      results do not indicate how CLIC1 undergoes a radical conformational change to
      form a transmembrane chloride channel but further elucidate the mechanism by
      which CLICs are redox controlled. 

PMID- 24089666
TI  - Soluble form of canine transferrin receptor inhibits canine parvovirus infection
      in vitro and in vivo.
AB  - Canine parvovirus (CPV) disease is an acute, highly infectious disease
      threatening the dog-raising industry. So far there are no effective therapeutic
      strategies to control this disease. Although the canine transferrin receptor
      (TfR) was identified as a receptor for CPV infection, whether extracellular
      domain of TfR (called soluble TfR (sTfR)) possesses anti-CPV activities remains
      elusive. Here, we used the recombinant sTfR prepared from HEK293T cells with
      codon-optimized gene structure to investigate its anti-CPV activity both in vitro
      and in vivo. Our results indicated that codon optimization could significantly
      improve sTfR expression in HEK293T cells. The prepared recombinant sTfR possessed
      a binding activity to both CPV and CPV VP2 capsid proteins and significantly
      inhibited CPV infection of cultured feline F81 cells and decreased the mortality
      of CPV-infected dogs, which indicates that the sTfR has the anti-CPV activity
      both in vitro and in vivo. 

PMID- 24089667
TI  - Synthesis, characterisation, and in vitro anticancer activity of curcumin
      analogues bearing pyrazole/pyrimidine ring targeting EGFR tyrosine kinase.
AB  - In search of potential therapeutics for cancer, we described herein the
      synthesis, characterization, and in vitro anticancer activity of a novel series
      of curcumin analogues. The anticancer effects were evaluated on a panel of 60
      cell lines, according to the National Cancer Institute (NCI) screening protocol.
      There were 10 tested compounds among 14 synthesized compounds, which showed
      potent anticancer activity in both one-dose and 5-dose assays. The most active
      compound of the series was 3,5-bis(4-hydroxy-3-methylstyryl)-1H-pyrazole-1
      yl(phenyl)methanone which showed mean growth percent of -28.71 in one-dose assay
      and GI50 values between 0.0079 and 1.86 uM in 5-dose assay.

PMID- 24089668
TI  - What is the role of apelin regarding cardiovascular risk and progression of renal
      disease in type 2 diabetic patients with diabetic nephropathy?
AB  - AIMS: To evaluate the association of different apelin levels with cardiovascular
      mortality, hospitalization, renal function, and cardiovascular risk factors in
      type 2 diabetic patients with mild to moderate CKD. METHODS: An observational,
      prospective study involving 150 patients divided into groups according to
      baseline apelin levels: 1 <= 98 pg/mL, 2 = 98-328 pg/mL, and 3 >= 329 pg/mL.
      Baseline characteristics were analyzed and compared. Multivariate Cox regression
      was used to find out predictors of cardiovascular mortality, and multivariate
      logistic regression was used to find out predictors of hospitalization and
      disease progression. Simple linear regressions and Pearson correlations were used
      to investigate correlations between apelin and renal disease and cardiovascular
      risk factors. RESULTS: Patients' survival at 83 months in groups 1, 2, and 3 was
      39%, 40%, and 71.2%, respectively (P = 0.046). Apelin, age, and eGFR were
      independent predictors of mortality, and apelin, creatinine, eGFR, resistin, and
      visfatin were independent predictors of hospitalization. Apelin levels were
      negatively correlated with cardiovascular risk factors and positively correlated
      with eGFR. Patients with lower apelin levels were more likely to start a
      depurative technique. CONCLUSIONS: Apelin levels might have a significant
      clinical use as a marker/predictor of cardiovascular mortality and
      hospitalization or even as a therapeutic agent for CKD patients with
      cardiovascular disease.

PMID- 24089670
TI  - Chair-based exercises for frail older people: a systematic review.
AB  - INTRODUCTION: Frail older people are often unable to undertake high-intensity
      exercise programmes. Chair-based exercises (CBEs) are used as an alternative, for
      which health benefits are uncertain. OBJECTIVE: To examine the effects of CBE
      programmes for frail older people through a systematic review of existing
      literature. METHOD: A systematic search was performed for CBE-controlled trials
      in frail populations aged >=65 years published between 1990 and February 2011 in
      electronic databases. Quality was assessed using the Jadad method. RESULTS: The
      search identified 164 references: with 42 duplicates removed, 122 reviewed, 116
      excluded, and 6 analysed. 26 outcome measures were reported measuring 3 domains:
      mobility and function, cardiorespiratory fitness, mental health. All studies were
      of low methodological quality (Jadad score <=2; possible range 0-5). Two studies
      showed no benefit, and four reported some evidence of benefit in all three
      domains. No harmful effects were reported; compliance was generally good.
      CONCLUSION: The quality of the evidence base for CBEs is low with inconclusive
      findings to clearly inform practice. A consensus is required on the definition
      and purpose of CBEs. Large well-designed randomised controlled trials to test the
      effectiveness of CBE are justified.

PMID- 24089669
TI  - Pharmacophore modeling and docking studies on some nonpeptide-based caspase-3
      inhibitors.
AB  - Neurodegenerative disorders are major consequences of excessive apoptosis caused
      by a proteolytic enzyme known as caspase-3. Therefore, caspase-3 inhibition has
      become a validated therapeutic approach for neurodegenerative disorders. We
      performed pharmacophore modeling on some synthetic derivatives of caspase-3
      inhibitors (pyrrolo[3,4-c]quinoline-1,3-diones) using PHASE 3.0. This resulted in
      the common pharmacophore hypothesis AAHRR.6 which might be responsible for the
      biological activity: two aromatic rings (R) mainly in the quinoline nucleus, one
      hydrophobic (H) group (CH3), and two acceptor (A) groups (-C=O). After
      identifying a valid hypothesis, we also developed an atom-based 3D-QSAR model
      applying the PLS algorithm. The developed model was statistically robust (q2 =
      0.53; pred_r2 = 0.80). Additionally, we have performed molecular docking studies,
      cross-validated our results, and gained a deeper insight into its molecular
      recognition process. Our developed model may serve as a query tool for future
      virtual screening and drug designing for this particular target.

PMID- 24089672
TI  - Postelimination status of childhood leprosy: report from a tertiary-care hospital
      in South India.
AB  - INTRODUCTION: Leprosy, a statistically "eliminated" disease from the globe,
      continues to linger around in its endemic countries including India. OBJECTIVE:
      This study describes the epidemiological and clinicopathological pattern of the
      disease seen in children over a period of 8 years following its elimination in
      India. MATERIALS AND METHODS: Medical records of all leprosy cases up to 14 years
      of age registered between April 2005 and March 2013 were retrospectively
      analyzed. Data were retrieved using a predesigned proforma and entered into the
      database system for analysis. RESULTS: Child proportion of newly registered
      leprosy cases did not show a significant decline in the years following its
      elimination. The disease seemed to manifest frequently in older children with an
      insignificant gender predilection. More than half of child cases had a history of
      household contact. Paucibacillary leprosy dominated in them with a solitary skin
      lesion as the most frequent presentation. Although nerve thickening was seen in
      nearly half of these children, neuritis and lepra reactions were less common.
      Deformity at the time of diagnosis was noted in 13.89% of cases. Although smear
      positivity was not a common feature in children affected with leprosy, a good
      clinicohistopathological correlation was observed in those who underwent biopsy.
      CONCLUSION: Our study and reports from different parts of the country depict the
      unturned curves in the epidemiology of childhood leprosy which mirrors active
      transmission in the community, lacunae in diagnosis, and the need to strengthen
      contact screening activities in the pediatric population to sustain elimination.

PMID- 24089671
TI  - Total marrow irradiation as part of autologous stem cell transplantation for
      Asian patients with multiple myeloma.
AB  - To compare the outcomes of melphalan 200 mg/m2 (HDM200) and 8 Gy total marrow
      irradiation (TMI) delivered by helical tomotherapy plus melphalan 140 mg/m2
      (HDM140 + TMI 8 Gy) in newly diagnosed symptomatic multiple myeloma (MM) Asian
      patients. Between 2007 and 2010, nine consecutive myeloma patients who were
      scheduled to undergo autologous stem cell transplantation (ASCT) were studied.
      The patients received three cycles of vincristine-adriamycin-dexamethasone (VAD)
      regimen as induction chemotherapy, and if they had a partial response, peripheral
      blood stem cells were collected by dexamethasone-etoposide-cyclophosphamide
      cisplatin (DECP). In arm A, six patients received the HDM200. In arm B, three
      patients received HDM140 + TMI 8 Gy. In arm B, the neutropenic duration was
      slightly longer than in arm A (P = 0.048). However, hematologic recovery (except
      for neutrophils), transfusion requirement, median duration of hospitalization,
      and the dose of G-CSF were similar in both arms. The median duration of overall
      survival and event-free survival was similar in the two arms (P = 0.387). As a
      conditioning regiment, HDM140 + TMI 8 Gy provide another chance for MM Asian
      patients who were not feasible for HDM200.

PMID- 24089673
TI  - High-level expression of functionally active dengue-2 non-structural antigen 1
      production in Escherichia coli.
AB  - Detection of nonstructural protein (NS1) is an important diagnostic marker during
      acute phase of dengue infection. Not only for diagnostic purpose, the protein had
      important role in vaccine design as well, as a candidate for studying virus
      assembly and maturation. Various researchers employed different expression
      systems and strategies for recombinant NS1 protein production. Attempts to
      express NS1 protein in prokaryotic and yeast expression system result in
      formation of insoluble protein which needs to undergo refolding to attain native
      structural and functional forms. Here, we report the production of soluble NS1
      protein in E. coli by using appropriate vector and employing suitable culture
      conditions to maximize protein production. Proteins were purified using metal
      affinity chromatography. SDS-PAGE and western blot analysis reveal the native
      structure of NS1 protein. Solid phase ELISA using the recombinantly expressed
      antigen with positive and negative dengue samples showed that the expressed
      protein retains its antigenic and immunological properties. To our knowledge,
      this is the first report on the successful production of functionally active
      recombinant dengue-2 NS1 protein production without undergoing any in vitro
      posttranslational modification process. 

PMID- 24089674
TI  - Neuroprotective effects of microRNA-210 on hypoxic-ischemic encephalopathy.
AB  - OBJECTIVES: To reveal the effect of microRNA-210 on cell apoptosis caused by HIE.
      METHODS: Postnatal day 7 rats after HI injury were intraventricularly injected
      with microRNA-210 mimic, microRNA-210 inhibitor, or physiological saline. 72 h
      after the injection, rats were sacrificed and the left hemispheres were
      collected. The expression level of microRNA-210 was identified by quantitative
      real-time PCR analysis. Apoptosis in brain sections was investigated by TUNEL
      assay. Apoptosis-related protein expressions were studied by Western blot
      analysis. RESULTS: The results showed that microRNA-210, whose expression was
      downregulated in the brain 72 h after HI injury, suppressed neuronal apoptosis by
      inhibiting caspase activity and regulating the balance between bcl-2 and bax
      levels. DISCUSSION: Recent study demonstrated that microRNA-210 has
      neuroprotective effects through inhibiting apoptosis in a murine model of HIE. It
      represents a potential novel therapeutic approach for the treatment of HIE.

PMID- 24089675
TI  - Predictors for increasing eligibility level among home help service users in the
      Japanese long-term care insurance system.
AB  - OBJECTIVES: This cross-sectional study described the prevalence of possible risk
      factors for increasing eligibility level of long-term care insurance in home help
      service users who were certified as support level 1-2 or care level 1-2 in Japan.
      METHODS: Data were collected from October 2011 to November 2011. Variables
      included eligibility level, grip strength, calf circumference (CC), functional
      limitations, body mass index, memory impairment, depression, social support, and
      nutrition status. RESULTS: A total of 417 subjects (109 males and 308 females,
      mean age 83 years) were examined. There were 109 subjects with memory impairment.
      When divided by cut-off values, care level 2 was found to have higher prevalence
      of low grip strength, low CC, and depression. CONCLUSIONS: Some potentially
      modifiable factors such as muscle strength could be the risk factors for
      increasing eligibility level.

PMID- 24089676
TI  - Lignocellulosic fermentation of wild grass employing recombinant hydrolytic
      enzymes and fermentative microbes with effective bioethanol recovery.
AB  - Simultaneous saccharification and fermentation (SSF) studies of steam exploded
      and alkali pretreated different leafy biomass were accomplished by recombinant
      Clostridium thermocellum hydrolytic enzymes and fermentative microbes for
      bioethanol production. The recombinant C. thermocellum GH5 cellulase and GH43
      hemicellulase genes expressed in Escherichia coli cells were grown in repetitive
      batch mode, with the aim of enhancing the cell biomass production and enzyme
      activity. In batch mode, the cell biomass (A(600 nm)) of E. coli cells and enzyme
      activities of GH5 cellulase and GH43 hemicellulase were 1.4 and 1.6 with 2.8 and
      2.2 U.mg-1, which were augmented to 2.8 and 2.9 with 5.6 and 3.8 U.mg-1 in
      repetitive batch mode, respectively. Steam exploded wild grass (Achnatherum
      hymenoides) provided the best ethanol titres as compared to other biomasses.
      Mixed enzyme (GH5 cellulase, GH43 hemicellulase) mixed culture (Saccharomyces
      cerevisiae, Candida shehatae) system gave 2-fold higher ethanol titre than single
      enzyme (GH5 cellulase) single culture (Saccharomyces cerevisiae) system employing
      1% (w/v) pretreated substrate. 5% (w/v) substrate gave 11.2 g.L-1 of ethanol at
      shake flask level which on scaling up to 2 L bioreactor resulted in 23 g.L-1
      ethanol. 91.6% (v/v) ethanol was recovered by rotary evaporator with 21.2%
      purification efficiency.

PMID- 24089677
TI  - Endostatin/collagen XVIII is increased in cerebrospinal fluid after severe
      traumatic brain injury.
AB  - Recent studies have suggested that endogenous angiogenesis inhibitor
      endostatin/collagen XVIII might play an important role in the secondary brain
      injury following traumatic brain injury (TBI). In this study, we measured
      endostatin/collagen XVIII concentrations serially for 1 week after
      hospitalization by using the enzyme-linked immunosorbent assay method in the
      cerebrospinal fluid (CSF) of 30 patients with TBI and a Glasgow Coma Scale (GCS)
      score of 8 or less on admission. There was a significant trend toward increased
      CSF levels of endostatin after TBI versus control from 72 h after injury. In
      patients with GCS score of 3-5, CSF endostatin concentration was substantially
      higher at 72 h after injury than that in patients with GCS score of 6-8 (P <
      0.05) and peaked rapidly at day 5 after injury, but decreased thereafter. The CSF
      endostatin concentration in 12 patients with an unfavorable outcome was
      significantly higher than that in 18 patients with a favorable outcome at day 5
      (P = 0.043) and day 7 (P = 0.005) after trauma. Receiver operating characteristic
      curve analysis suggested a reliable operating point for the 7-day CSF endostatin
      concentration predicting poor prognosis to be 67.29 pg/mL. Our preliminary
      findings provide new evidence that endostatin/collagen XVIII concentration in the
      CSF increases substantially in patients with sTBI. Its dynamic change may have
      some clinical significance on the judgment of brain injury severity and the
      assessment of prognosis. This trial is registered with the ClinicalTrials.gov
      Identifier: NCT01846546. 

PMID- 24089678
TI  - Creation of an adiposity index for children aged 6-8 years: the Gateshead
      Millennium Study.
AB  - OBJECTIVE: A number of measures of childhood adiposity are in use, but all are
      relatively imprecise and prone to bias. We constructed an adiposity index (AI)
      using a number of different measures. METHODS: Detailed body composition data on
      460 of the Gateshead Millennium Study cohort at the age of 6-8 years were
      analysed. The AI was calculated using factor analysis on age plus thirteen
      measures of adiposity and/or size. Correlations between these variables, the AI,
      and more traditional measures of adiposity in children were investigated.
      RESULTS: Based on the factor loading sizes, the first component, taken to be the
      AI, consisted mainly of measures of fat-mass (the skinfold measurements, fat mass
      score, and waist circumference). The second comprised variables measuring frame
      size, while the third consisted mainly of age. The AI had a high correlation with
      body mass index (BMI) (rho = 0.81). CONCLUSIONS: While BMI is practical for
      assessing adiposity in children, the AI combines a wider range of data related to
      adiposity than BMI alone and appears both valid and valuable as a research tool
      for studies of childhood adiposity. Further research is necessary to investigate
      the utility of AI for research in other samples of children and also in adults.

PMID- 24089679
TI  - Characterization of schizophrenia adverse drug interactions through a network
      approach and drug classification.
AB  - Antipsychotic drugs are medications commonly for schizophrenia (SCZ) treatment,
      which include two groups: typical and atypical. SCZ patients have multiple
      comorbidities, and the coadministration of drugs is quite common. This may result
      in adverse drug-drug interactions, which are events that occur when the effect of
      a drug is altered by the coadministration of another drug. Therefore, it is
      important to provide a comprehensive view of these interactions for further
      coadministration improvement. Here, we extracted SCZ drugs and their adverse drug
      interactions from the DrugBank and compiled a SCZ-specific adverse drug
      interaction network. This network included 28 SCZ drugs, 241 non-SCZs, and 991
      interactions. By integrating the Anatomical Therapeutic Chemical (ATC)
      classification with the network analysis, we characterized those interactions.
      Our results indicated that SCZ drugs tended to have more adverse drug
      interactions than other drugs. Furthermore, SCZ typical drugs had significant
      interactions with drugs of the "alimentary tract and metabolism" category while
      SCZ atypical drugs had significant interactions with drugs of the categories
      "nervous system" and "antiinfectives for systemic uses." This study is the first
      to characterize the adverse drug interactions in the course of SCZ treatment and
      might provide useful information for the future SCZ treatment.

PMID- 24089680
TI  - Removal of white mineral trioxide aggregate cement: a promising approach.
AB  - Removal of MTA from dentin by applying 37% hydrochloric acid (HCl) to reduce
      microhardness and push-out bond strength. Forty dentin slices were filled with
      WMTA and divided into two groups (n = 20). Ten slices remained untreated while
      others were exposed to either HCl or phosphate buffer saline (PBS) and all
      samples were subjected to pushout test. The mode of bond failures was determined
      by SEM analysis. Later, twenty glass tubes were filled with WMTA and divided into
      two groups (n = 10). One side of tube was exposed to HCl or PBS while the other
      side remained untreated and the microhardness was analyzed by testing machine.
      HCl showed significantly lower pushout strength and microhardness values (P =
      0.0001), (P = 0.0001). HCl treated samples showed mixed bond failures dominantly,
      while PBS samples mostly showed adhesive failures. The results of this study can
      suggest the 37% HCl as an effective solution to aid the removal of MTA from the
      dentin surfaces. 

PMID- 24089681
TI  - A biosurfactant-sophorolipid acts in synergy with antibiotics to enhance their
      efficiency.
AB  - Sophorolipids (SLs), biosurfactants with antimicrobial properties, have been
      tried to address the problem of antibiotic resistance. The synergistic action of
      SL and antibiotics was checked using standard microdilution and spread plate
      methods. With Staphylococcus aureus, SL-tetracycline combination achieved total
      inhibition before 4 h of exposure while tetracycline alone couldnot achieve total
      inhibition till the end of 6 h. The inhibition caused by exposure of bacterium to
      SL-tetracycline mixture was ~25% more as compared to SL alone. In spite of known
      robustness of gram-negative bacteria, SL-cefaclor mixture proved to be efficient
      against Escherichia coli which showed ~48% more inhibition within 2 h of exposure
      as compared to cefaclor alone. Scanning electron microscopy of the cells treated
      with mixture revealed bacterial cell membrane damage and pore formation.
      Moreover, SLs being a type of asymmetric bola, they are expected to form self
      assemblies with unique functionality. This led to the speculation that SLs being
      amphiphilic in nature can span through the structurally alike cell membrane and
      facilitate the entry of drug molecules. 

PMID- 24089682
TI  - In vitro cytotoxic, antioxidant, and antimicrobial activities of Mesua beccariana
      (Baill.) Kosterm., Mesua ferrea Linn., and Mesua congestiflora extracts.
AB  - The in vitro cytotoxicity tests on the extracts of Mesua beccariana, M. ferrea,
      and M. congestiflora against Raji, SNU-1, HeLa, LS-174T, NCI-H23, SK-MEL-28, Hep
      G2, IMR-32, and K562 were achieved using MTT assay. The methanol extracts of
      Mesua beccariana showed its potency towards the proliferation of B-lymphoma cell
      (Raji). In addition, only the nonpolar to semipolar extracts (hexane to ethyl
      acetate) of the three Mesua species indicated cytotoxic effects on the tested
      panel of human cancer cell lines. Antioxidant assays were evaluated using DPPH
      scavenging radical assay and Folin-Ciocalteu method. The methanol extracts of M.
      beccariana and M. ferrea showed high antioxidant activities with low EC50 values
      of 12.70 and 9.77  MUg/mL, respectively, which are comparable to that of ascorbic
      acid (EC50 = 5.62  MUg/mL). Antibacterial tests were carried out using four Gram
      positive and four Gram negative bacteria on Mesua beccariana extracts. All the
      extracts showed negative results in the inhibition of Gram negative bacteria.
      Nevertheless, methanol extracts showed some activities against Gram positive
      bacteria which are Bacillus cereus, methicillin-sensitive Staphylococcus aureus
      (MSSA), and methicillin-resistant Staphylococcus aureus (MRSA), while the hexane
      extract also contributed some activities towards Bacillus cereus.

PMID- 24089683
TI  - Angiotensin II AT1 receptors are involved in neuronal activation induced by
      amphetamine in a two-injection protocol.
AB  - It was already found that Ang II AT1 receptors are involved in the
      neuroadaptative changes induced by a single exposure to amphetamine, and such
      changes are related to the development of behavioral and neurochemical
      sensitization. The induction of the immediately early gene c-fos has been used to
      define brain activated areas by amphetamine. Our aim was to evaluate the
      participation of AT1 receptors in the neuronal activation induced by amphetamine
      sensitization. The study examined the c-fos expression in mesocorticolimbic areas
      induced by amphetamine challenge (0.5 mg/kg i.p) in animals pretreated with
      candesartan, a selective AT1 receptor blocker (3 mg/kg p.o * 5 days), and
      amphetamine (5 mg/kg i.p) 3 weeks before the challenge. Increased c-fos
      immunoreactivity was found in response to the amphetamine challenge in the
      dorsomedial caudate-putamen and nucleus accumbens, and both responses were
      blunted by the AT1 receptor blocker pretreatment. In the infralimbic prefrontal
      cortex, increased c-fos immunoreactivity was found in response to amphetamine and
      saline challenge, and both were prevented by the AT1 receptor blocker. No
      differences were found neither in ventral tegmental area nor prelimbic cortex
      between groups. Our results indicate an important role for brain Ang II in the
      behavioral and neuronal sensitization induced by amphetamine.

PMID- 24089684
TI  - Clinical prediction of deeply infiltrating endometriosis before surgery: is it
      feasible? A review of the literature.
AB  - BACKGROUND: Endometriosis is a chronic benign gynecologic disease that can cause
      pelvic pain and infertility affecting almost 10% of reproductive-age women.
      Deeply infiltrating endometriosis (DIE) is a specific entity responsible for
      painful symptoms which are related to the anatomic location of the lesions.
      Definitive diagnosis requires surgery, and histological confirmation is
      advisable. The aim of this paper is to review the current literature regarding
      the possibility of diagnosing DIE accurately before surgery. Despite its low
      sensitivity and specificity, vaginal examination and evaluation of specific
      symptoms should not be completely omitted as a basic diagnostic tool in detecting
      endometriosis and planning further therapeutic interventions. Recently,
      transvaginal ultrasound (TVUS) has been reported as an excellent tool to diagnose
      DIE lesions in different locations (rectovaginal septum, retrocervical and
      paracervical areas, rectum and sigmoid, and vesical wall) with good accuracy.
      CONCLUSION: There are neither sufficiently sensitive and specific signs and
      symptoms nor diagnostic tests for the clinical diagnosis of DIE, resulting in a
      great delay between onset of symptoms and diagnosis. Digital examination, in
      addition to TVS, may help to gain better understanding of the anatomical extent
      and dimension of DIE which is of crucial importance in defining the best surgical
      approach.

PMID- 24089685
TI  - Fitness cost of Litomosoides sigmodontis filarial infection in mite vectors;
      implications of infected haematophagous arthropod excretory products in host
      vector interactions.
AB  - Filariae are a leading cause of infections which are responsible for serious
      dermatological, ocular, and vascular lesions. Infective third stage larvae (L3)
      are transmitted through the bite of a haematophagous vector. Litomosoides
      sigmodontis is a well-established model of filariasis in the mouse, with the
      vector being the mite Ornithonyssus bacoti. The aim of the study was to analyse
      the filarial infection in mites to determine the consequences of filarial
      infection in the blood-feeding and the reproduction of mites as well as in the
      regulation of vector-induced inflammation in the mouse skin. Firstly, L3 are
      unevenly distributed throughout the host population and the majority of the
      population harbours a moderate infection (1 to 6 L3). Filarial infection does not
      significantly affect the probing delay for blood feeding. The number of released
      protonymphs is lower in infected mites but is not correlated with the L3 burden.
      Finally, induced excreted proteins from infected mites but not from uninfected
      mites stimulate TNF- alpha and the neutrophil-chemoattractant KC production by
      antigen-presenting cells (APCs). Altogether, these results describe the
      modification of the mite behavior under filarial infection and suggest that the
      immunomodulatory capacity of the mite may be modified by the presence of the
      parasite, hindering its defensive ability towards the vertebrate host. 

PMID- 24089686
TI  - Immunocytochemical characterization of Alzheimer disease hallmarks in APP/PS1
      transgenic mice treated with a new anti-amyloid-beta vaccine.
AB  - APP/PS1 double-transgenic mouse models of Alzheimer's disease (AD), which
      overexpress mutated forms of the gene for human amyloid precursor protein (APP)
      and presenilin 1 (PS1), have provided robust neuropathological hallmarks of AD
      like pattern at early ages. This study characterizes immunocytochemical patterns
      of AD mouse brain as a model for human AD treated with the EB101 vaccine. In this
      novel vaccine, a new approach has been taken to circumvent past failures by
      judiciously selecting an adjuvant consisting of a physiological matrix embedded
      in liposomes, composed of naturally occurring phospholipids (phosphatidylcholine,
      phosphatidylglycerol, and cholesterol). Our findings showed that administration
      of amyloid-beta1-42 (Abeta) and sphingosine-1-phosphate emulsified in liposome
      complex (EB101) to APP/PS1 mice before onset of Abeta deposition (7 weeks of age)
      and/or at an older age (35 weeks of age) is effective in halting the progression
      and clearing the AD-like neuropathological hallmarks. Passive immunization with
      EB101 did not activate inflammatory responses from the immune system and
      astrocytes. Consistent with a decreased inflammatory background, the basal
      immunological interaction between the T cells and the affected areas
      (hippocampus) in the brain of treated mice was notably reduced. These results
      demonstrate that immunization with EB101 vaccine prevents and attenuates AD
      neuropathology in this type of double-transgenic mice.

PMID- 24089687
TI  - A prospective profile of visual field loss following stroke: prevalence, type,
      rehabilitation, and outcome.
AB  - AIMS: To profile site of stroke/cerebrovascular accident, type and extent of
      field loss, treatment options, and outcome. METHODS: Prospective multicentre
      cohort trial. Standardised referral and investigation protocol of visual
      parameters. RESULTS: 915 patients were recruited with a mean age of 69 years (SD
      14). 479 patients (52%) had visual field loss. 51 patients (10%) had no visual
      symptoms. Almost half of symptomatic patients (n = 226) complained only of visual
      field loss: almost half (n = 226) also had reading difficulty, blurred vision,
      diplopia, and perceptual difficulties. 31% (n = 151) had visual field loss as
      their only visual impairment: 69% (n = 328) had low vision, eye movement
      deficits, or visual perceptual difficulties. Occipital and parietal lobe strokes
      most commonly caused visual field loss. Treatment options included visual search
      training, visual awareness, typoscopes, substitutive prisms, low vision aids,
      refraction, and occlusive patches. At followup 15 patients (7.5%) had full
      recovery, 78 (39%) had improvement, and 104 (52%) had no recovery. Two patients
      (1%) had further decline of visual field. Patients with visual field loss had
      lower quality of life scores than stroke patients without visual impairment.
      CONCLUSIONS: Stroke survivors with visual field loss require assessment to
      accurately define type and extent of loss, diagnose coexistent visual
      impairments, and offer targeted treatment.

PMID- 24089688
TI  - Identifying cell class specific losses from serially generated electroretinogram
      components.
AB  - PURPOSE: Processing of information through the cellular layers of the retina
      occurs in a serial manner. In the electroretinogram (ERG), this complicates
      interpretation of inner retinal changes as dysfunction may arise from "upstream"
      neurons or may indicate a direct loss to that neural generator. We propose an
      approach that addresses this issue by defining ERG gain relationships. METHODS:
      Regression analyses between two serial ERG parameters in a control cohort of rats
      are used to define gain relationships. These gains are then applied to two models
      of retinal disease. RESULTS: The PIII(amp) to PII(amp) gain is unity whereas the
      PII(amp) to pSTR(amp) and PII(amp) to nSTR(amp) gains are greater than unity,
      indicating "amplification" (P < 0.05). Timing relationships show amplification
      between PIII(it) to PII(it) and compression for PII(it) to pSTR(it) and PII(it)
      to nSTR(it), (P < 0.05). Application of these gains to omega-3-deficiency
      indicates that all timing changes are downstream of photoreceptor changes, but a
      direct pSTR amplitude loss occurs (P < 0.05). Application to diabetes indicates
      widespread inner retinal dysfunction which cannot be attributed to outer retinal
      changes (P < 0.05). CONCLUSIONS: This simple approach aids in the interpretation
      of inner retinal ERG changes by taking into account gain characteristics found
      between successive ERG components of normal animals.

PMID- 24089689
TI  - Neurocognitive functioning in schizophrenia and during the early phases of
      psychosis: targeting cognitive remediation interventions.
AB  - Recent interest in the early course of schizophrenia accentuated altered
      cognition prior to the onset. Ultrahigh risk (UHR) individuals with attenuated
      positive symptoms and transient psychotic episodes demonstrate neurocognitive
      deficits across multiple domains such as memory, executive functioning, and
      processing speed which are consistent with similar disturbances identified in
      patients with a first episode of schizophrenia. Cognitive remediation (CR)
      approaches representing a broad set of activities are aimed to restore or improve
      cognitive functioning. CR proved to be effective in modulating the cognitive
      dysfunction in schizophrenia but is rarely used in ultrahigh risk individuals.
      From the clinical prospective, a better understanding of cognitive functioning in
      at-risk states is essential for the development of optimal early intervention
      models. In the review, we highlight the intervention targets, notably the
      specific cognitive deficits in at risk individuals which preceed the transition
      to psychosis and emphasize the need of the additional studies using CR approaches
      in UHR group aiming to enhance cognition and therefore mediate functional
      improvement. 

PMID- 24089690
TI  - Optimization of dairy sludge for growth of Rhizobium cells.
AB  - In this study dairy sludge was evaluated as an alternative cultivation medium for
      Rhizobium. Growth of bacterial strains at different concentrations of Dairy
      sludge was monitored. Maximum growth of all strains was observed at 60% Dairy
      sludge concentration. At 60% optical density (OD) values are 0.804 for Rhizobium
      trifolii (MTCC905), 0.825 for Rhizobium trifolii (MTCC906), and 0.793 for
      Rhizobium meliloti (MTCC100). Growth pattern of strains was observed at 60% Dairy
      sludge along with different synthetic media (tryptone yeast, Rhizobium minimal
      medium and yeast extract mannitol). Growth in 60% Dairy sludge was found to be
      superior to standard media used for Rhizobium. Media were optimized using 60%
      dairy sludge along with different concentrations of yeast extract (1-7 g/L) and
      mannitol (7-13 g/L) in terms of optical density at different time intervals, that
      is, 24, 48 and 72 hours. Maximum growth was observed in 6 g/L of yeast extract
      and 12 g/L of mannitol at 48-hour incubation period in all strains. The important
      environmental parameters such as pH were optimized using 60% dairy sludge, 60%
      dairy sludge +6 g/L yeast extract, and 60% dairy sludge +12 g/L mannitol. The
      maximum growth of all strains was found at pH 7.0. The present study recommends
      the use of 60% dairy sludge as a suitable growth medum for inoculant production. 

PMID- 24089691
TI  - Effectiveness of naltrexone in the prevention of delayed respiratory arrest in
      opioid-naive methadone-intoxicated patients.
AB  - Acute methadone toxicity is a major public health concern in Iran. Methadone
      intoxicated patients are in a great risk of recurrent or delayed respiratory
      arrest despite the prescription of initial doses of naloxone. This study aimed to
      evaluate the effectiveness of oral naltrexone in the management of acute
      methadone overdose in opioid-naive patients and check if it could be a substitute
      of continuous infusion of naloxone in maintaining adequate ventilation. In a
      randomized, double-blind, placebo-controlled study, a total of 54 opioid-naive
      patients with acute methadone toxicity were enrolled. The patients received
      either oral naltrexone or placebo capsules after awakening by naloxone. All
      patients underwent close monitoring of respiration. Frequency of respiratory
      depression or arrest, need for another dose of naloxone, duration of hospital
      stay, and adverse outcomes compared between the two groups. The incidence of
      respiratory depression was significantly less in those who had received
      naltrexone. Our results show that single oral dose of naltrexone is quite
      efficient in the prevention of recurrent or delayed respiratory arrest in opioid
      naive methadone-intoxicated patients. It can shorten the duration of
      hospitalization and, as a consequence, decreased the risk of complications.
      Further studies are warranted before the generalization of this approach to other
      patient populations. 

PMID- 24089692
TI  - Transforaminal lumbar interbody fusion using a modified distractor handle: a
      midterm clinicoradiological follow-up study.
AB  - In current TLIF practice, the choice of the cage size is empirical and primarily
      depends on the case volume and experience of the surgeon. We used a self-made
      modified distractor handle in TLIF procedure with the goal of standardizing the
      intervertebral space tension and determining the proper cage size. 

PMID- 24089695
TI  - Synergistically enhanced electrochemical response of host-guest recognition based
      on ternary nanocomposites: reduced graphene oxide-amphiphilic pillar[5]arene-gold
      nanoparticles.
AB  - An amphiphilic pillar[5]arene (AP5) was modified onto the surface of reduced
      graphene oxide (RGO) to form the water-dispersive RGO-AP5 nanocomposite. And
      then, as-prepared gold nanoparticles (AuNPs) self-assembled onto the surface of
      RGO-AP5 through amido groups of AP5 to achieve RGO-AP5-AuNPs nanocomposites. It
      was verified that a large amount of AP5 molecules had been effectively loaded
      onto the surface of RGO and lots of AuNPs could be uniformly dispersed on RGO
      AP5. Electrochemical results showed that the RGO-AP5 could exhibit selective
      supramolecular recognition and enrichment capability toward guest molecules. More
      significantly, in electrochemical sensing the guest molecules, ternary
      nanocomposites RGO-AP5-AuNPs performed the synergetic action of multifunctional
      properties, which were excellent performances of RGO, selective supramolecular
      recognition, and enrichment capability of AP5 and catalytic property of AuNPs for
      guest molecules. Therefore, RGO-AP5-AuNPs showed an outstanding analyzing
      performance for DA with broad linear range (1.5 * 10(-8) to 1.9*10(-5) M) and low
      detection limit (1.2 * 10(-8) M) at a signal-to-noise ratio of 3. 

PMID- 24089693
TI  - A randomized controlled trial of two different lengths of nicotine replacement
      therapy for smoking cessation.
AB  - This study examined if 2-week free nicotine replacement therapy (NRT) would be
      more effective than 1-week free NRT to help smokers quit smoking at 6 and 12
      months. In a single-blinded randomized controlled trial design, 562 Chinese
      smokers who attended a smoking cessation clinic in Hong Kong, China, were
      randomly allocated into two groups (A1 and A2): A1 (n = 284) received behavioural
      counselling with free NRT for 1 week; A2 (n = 278) received similar counselling
      with free NRT for 2 weeks. All subjects received printed self-help materials to
      support their quitting efforts. A structured questionnaire was used for data
      collection, including pattern of NRT use and self-reported 7-day point prevalence
      quit rate at 6 months and 12 months. Among the participants, the mean number of
      cigarettes smoked per day was 18.8 (SD = 10.9). By intention-to-treat analysis, 7
      day point prevalence quit rates were not significantly different between A1 and
      A2 groups at 6-month (27.5% versus 27.3%; P = 0.97) and 12-month (21.1% versus
      21.2%; P = 0.98) followup. The findings suggest that two-week free NRT was not
      more effective than 1-week free NRT to increase smoking cessation rate among
      Chinese smokers. 

PMID- 24089696
TI  - Flow, packing and compaction properties of novel coprocessed multifunctional
      directly compressible excipients prepared from tapioca starch and mannitol.
AB  - Novel multifunctional excipients were prepared by coprocessing tapioca starch
      with mannitol using two methods viz; co-grinding and co-fusion. The flow, packing
      and compaction properties of the native and novel excipients were evaluated by
      using density, Hausner's ratio, angle of repose, the maximum volume reduction,
      consolidation index, the rate of consolidation, angle of internal friction,
      morphological properties, Heckel analysis, tensile strength and dilution
      potential as evaluation parameters. The study revealed that the method of
      coprocessing, particle size and particle shape influenced the properties of the
      resulting novel excipients. Co-grinding was less effective than co-fusion in the
      preparation of excipients with enhanced properties. The study concluded that
      coprocessing tapioca starch and mannitol will enhance the flow, packing and
      compaction properties of the novel excipient and that the co-fusion method of
      coprocessing would produce novel excipients with enhanced direct compression
      potential compared to the co-grinding method.

PMID- 24089697
TI  - Fetal tyhmus size as a predictor of histological chorioamnionitis in preterm
      premature rupture of membranes.
AB  - OBJECTIVE: To predict histological chorioamnionitis (CA) in the cases of preterm
      premature rupture of membranes by using fetal thymus transverse and
      anteroposterior diameters and areal measurements. METHODS: Fifty healthy and 50
      patients diagnosed with preterm premature rupture of membranes (PPROM) between 24
      and 37 weeks of gestation were included in the study. Fetal thymus measurements
      were done and repeated on a weekly basis until delivery, Furthermore white blood
      cell, erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP) levels
      were measured every other day until delivery, too. Following delivery, all
      patients' placentas were sent to pathology. RESULTS: Histological CA was detected
      in 48% of the PPROM patients. There were no patients in either group with
      clinical CA. Thymus transverse diameter had 91% sensitivity, 81% specificity, 82%
      PPV, and 91% NPV in predicting histological CA in PPROM patients. No linear
      relationship was found between thymus anteroposterior diameter measurements and
      gestational age. Thymus area measurements have sensitivity of 75%, specificity of
      81%, PPV of 78%, NPV of78% in determining CA in patients with PPROM. CONCLUSION:
      Both thymus transverse diameter and area measurement are more significant than
      sedimentation and CRP values in predicting histological CA. Fetal thymus
      measurements can be used in early diagnosis of infections among high risk
      patients.

PMID- 24089698
TI  - Suppression of adipogenesis and obesity in high-fat induced mouse model by
      hydroxylated polymethoxyflavones.
AB  - This study demonstrated that hydroxylated polymethoxyflavones (HPMFs) effectively
      and dose-dependently suppressed accumulation of lipid droplets in adipocytes by
      approximately 51-55%. Western blot analysis revealed that HPMFs markedly down
      regulated adipogenesis-related transcription factors peroxisome proliferator
      activated receptor (PPAR) gamma and sterol regulatory element-binding protein
      (SREBP)-1c as well as downstream target fatty acid binding protein 2 (aP2), fatty
      acid synthase (FAS), and acetyl-CoA carboxylase (ACC). In addition, HPMFs also
      activated adenosine monophosphate-activated protein kinase (AMPK) signaling in
      3T3-L1 adipocytes. In the early phase of adipogenesis, HPMF-treated preadipocytes
      displayed a delayed cell cycle entry into G2/M phase at 24 h (35.5% for DMI group
      and 4.8% for 20 MUg/mL HPMFs-treated group) after initiation of adipogenesis.
      Furthermore, administration of HPMFs (0.25 and 1%) decreased high-fat diet (HFD)
      induced weight gain (15.3 +/- 3.9 g for HFD group, 10.3 +/- 0.3 g and 7.9 +/- 0.7
      g for 0.25 and 1% HPMFs groups, respectively) and relative perigonadal,
      retroperitoneal, mesenteric fat weight in C57BL/6 mice. Administration of HPMFs
      reduced serum levels of aspartate aminotransferase (GOT), alanine
      aminotransferase (GPT), triglycerides (TG), and total cholesterol (T-cho). The
      results suggested that HPMFs may have a potential benefit in preventing obesity. 

PMID- 24089699
TI  - Specific binding of modified ZD6474 (Vandetanib) monomer and its dimer with VEGF
      receptor-2.
AB  - Tumor angiogenesis is an important component of cancer biology driven in part by
      the hypothesis that tumor vessel growth is a necessary requirement for tumor
      growth. Angiogenesis does not only depend on endothelial cell invasion and
      proliferation, it also requires pericyte coverage of vascular sprouts for vessel
      stabilization. These processes are coordinated by vascular endothelial growth
      factor (VEGF). Vandetanib, also known as ZD6474, is an orally bioavailable small
      molecule tyrosine kinase inhibitor of multiple growth factors that is an
      antagonist of the vascular endothelial growth factor receptor-2 (VEGFR-2). ZD6474
      was purchased and modified to add a fluorescent dye (6-FAM). A linker was used to
      couple the ZD6474 monomer to create dimers, and similarly linked to FAM
      fluorescent dye. The two compounds were compared using human endothelial cell
      (HUVECs) and the cancer cell lines U-87-MG and MDA-MB-231. We compared cellular
      uptake and binding specificity, as well as effects on cellular viability and
      angiogenesis in a series of in vitro and in vivo studies. ZD6474 dimer
      demonstrated improved uptake in HUVECs and other VEGFR expressing cells over
      ZD6474 monomer in vitro. Therapeutic effects were mixed, with in vitro studies
      showing the dimer having the same or weaker effects compared to the monomer,
      while an in vivo study using pseudotumors (matrigel plug assay) seemed to
      indicate stronger effects could be obtained from the dimer. Finally, in
      biodistribution study in a xenograft tumor model, the dimer accumulated 20*
      greater concentration in the tumor than in the liver, spleen, or kidneys, and
      also 20* greater than the accumulation of the monomer or the dye alone, all at 24
      h following compound injection. This study provides a rationale for the
      evaluation of dimeric ZD6474 as a potent imaging agent of angiogenic activity in
      vivo. 

PMID- 24089700
TI  - Novel therapeutic strategies using nanodrug delivery, stem cells and combination
      therapy for CNS trauma and neurodegenerative disorders.
AB  - The 10th Global College of Neuroprotection and Neuroregeneration Annual
      Conference in collaboration with the 6th International Association of
      Neurorestoratology VI Intercontinental Hotel, Bucharest, Romania, 4-7 April 2013
      The 10th Global College of Neuroproetction and Neuroregeneration Annual
      Conference together with the International Association of Neurorestoratology VI
      was held in Bucharest under the auspicious of the Society for the Study of
      Neuroprotection and Neuroplasticity during 4-7 April 2013. The focus of these
      unified societies meeting was on neurorestoration, neuroprotection and
      neuroregeneration in various clinical neurodegenerative diseases; for example,
      Alzheimer's, Parkinson's, Huntington's disease, stroke and brain or spinal cord
      injuries. The main aim to enhance healthcare was suggested by the use of stem
      cells, nanodrug delivery of drugs and stem cells, use of multimodal drugs as well
      as a combination of different approaches. The meeting was attended by more than
      500 delegates including researches, policy makers and healthcare professionals
      along with several representatives from drug industries from Europe and USA. It
      appears that future of neuroprotection could be achieved by the use of stem cells
      and nanodrug delivery in chronic neurological disorders. 

PMID- 24089701
TI  - Synthesis, magnetism, and 57Fe Mossbauer spectroscopic study of a family of
      [Ln3Fe7] coordination clusters (Ln = Gd, Tb, and Er).
AB  - The reaction of N-methydiethanolamine (mdeaH2), benzoic acid, FeCl3, and
      Ln(NO3)3.6H2O or LnCl3.xH2O yields a series of decanuclear coordination clusters,
      [Ln3Fe7(MU4-O)2(MU3-OH)2(mdea)7(MU-benzoate)4(N3)6].4MeCN.H2O, where Ln = Gd(III)
      (1) or Tb(III) (2), and [Er3Fe7(MU4-O)2(MU3-OH)2(mdea)7(MU
      benzoate)4(N3)5(MeOH)]Cl.7.5H2O.11.5MeOH (3). The isostructural compounds 1-3 all
      crystallize isotypically in the triclinic space group P1 with Z = 2, as does the
      previously reported dysprosium analogue 4. Six of the Fe(III) ions are
      pseudooctahedrally coordinated, whereas the seventh has a trigonal-bipyramidal
      coordination geometry. Temperature-dependent direct-current magnetic
      susceptibility studies indicate that intracluster antiferromagnetic interactions
      are dominant in 1-3. The frequency-dependent out-of-phase (chi") alternating
      current susceptibility reveals that 2 undergoes a slow relaxation of its
      magnetization, presumably resulting from anisotropy of the Tb(III) ions. Between
      30 and 295 K, the (57)Fe Mossbauer spectra reveal paramagnetic behavior with six
      partially resolved quadrupole doublets, one for the trigonal-bipyramidal Fe(III)
      site and five for the six pseudooctahedral Fe(III) sites. The Mossbauer spectra
      of 2 and 3 obtained between 3 and 30 K are consistent with the presence of
      Fe(III) intracluster antiferromagnetic coupling with slow magnetic relaxation
      relative to the Larmor precession time. Further, the observed changes in the
      effective magnetic field values in the spectra measured at 3 K with increasing
      applied field are consistent with the effect of the local spin polarization along
      the applied magnetic field direction, a behavior reminiscent of antiparallel spin
      coupled iron molecular paramagnetic systems. 

PMID- 24089702
TI  - Protocol for a systematic review of prognostic models for the recurrence of
      venous thromboembolism (VTE) following treatment for a first unprovoked VTE.
AB  - BACKGROUND: Venous thromboembolism (VTE) is a chronic disease, with fatal
      recurrences occurring in 5% to 9% of patients, yet it is also one of the best
      examples of preventable disease. Prognostic models that utilise multiple
      prognostic factors (demographic, clinical and laboratory patient characteristics)
      in combination to predict individual outcome risk may allow the identification of
      patients who would benefit from long-term anticoagulation therapy, and conversely
      those that would benefit from stopping such therapy due to a low risk of
      recurrence. The study will systematically review the evidence on potential
      prognostic models for the recurrence of VTE or adverse outcomes following the
      cessation of therapy, and synthesise and summarise each model's prognostic value.
      The review has been registered with PROSPERO (CRD42013003494). METHODS/DESIGN:
      Articles will be sought from the Cochrane library (CENTRAL, CDSR, DARE, HTA
      databases), MEDLINE and EMBASE. Trial registers will be searched for ongoing
      studies, and conference abstracts will be sought. Reference lists and subject
      experts will be utilised. No restrictions on language of publications will be
      applied. Studies of any design will be included if they examine, in patients
      ceasing therapy after at least three months' treatment with an oral anticoagulant
      therapy, whether more than one factor in combination is associated with the risk
      of VTE recurrence or another adverse outcome. Study quality will be assessed
      using appropriate guidelines for prognostic models. Prognostic models will be
      summarised qualitatively and, if tested in multiple validation studies, their
      predictive performance will be summarised using a random-effects meta-analysis
      model to account for any between-study heterogeneity. DISCUSSION: The results of
      the review will identify prognostic models for the risk of VTE recurrence or
      adverse outcome following cessation of therapy for a first unprovoked VTE. These
      will be informative for clinicians currently treating patients for a first
      unprovoked VTE and considering whether to stop treatment or not for particular
      individuals. The conclusions of the review will also inform the potential
      development of new prognostic models and clinical prediction rules to identify
      those at high or low risk of VTE recurrence or adverse outcome following a first
      unprovoked VTE.

PMID- 24089703
TI  - Inhibition of thyroid hormone sulfotransferase activity by brominated flame
      retardants and halogenated phenolics.
AB  - Many halogenated organic contaminants (HOCs) are considered endocrine disruptors
      and affect the hypothalamic-pituitary-thyroid axis, often by interfering with
      circulating levels of thyroid hormones (THs). We investigated one potential
      mechanism for TH disruption, inhibition of sulfotransferase activity. One of the
      primary roles of TH sulfation is to support the regulation of biologically active
      T3 through the formation of inactive THs. We investigated TH sulfotransferase
      inhibition by 14 hydroxylated polybrominated diphenyl ethers (OH BDEs), BDE 47,
      triclosan, and fluorinated, chlorinated, brominated, and iodinated analogues of
      2,4,6-trihalogenated phenol and bisphenol A (BPA). A new mass spectrometry-based
      method was also developed to measure the formation rates of 3,3'-T2 sulfate (3,3'
      T2S). Using pooled human liver cytosol, we investigated the influence of these
      HOCs on the sulfation of 3,3'-T2, a major substrate for TH sulfation. For the
      formation of 3,3'-T2S, the Michaelis constant (Km) was 1070 +/- 120 nM and the
      Vmax was 153 +/- 6.6 pmol min(-1) (mg of protein)(-1). All chemicals investigated
      inhibited sulfotransferase activity with the exception of BDE 47. The 2,4,6
      trihalogenated phenols were the most potent inhibitors followed by the OH BDEs
      and then halogenated BPAs. The IC50 values for the OH BDEs were primarily in the
      low nanomolar range, which may be environmentally relevant. In silico molecular
      modeling techniques were also used to simulate the binding of OH BDE to SULT1A1.
      This study suggests that some HOCs, including antimicrobial chemicals and
      metabolites of flame retardants, may interfere with TH regulation through
      inhibition of sulfotransferase activity. 

PMID- 24089704
TI  - Lupus-like oral mucosal lesions in mercury-induced autoimmune response in Brown
      Norway rats.
AB  - BACKGROUND: Administration of mercury at nontoxic doses induces systemic
      autoimmune disease in Brown Norway (BN) rats. The pathogenesis of lupus-like oral
      mucosal lesion by mercury-induced autoimmunity is still unclear, even though the
      oral mucosa is observed to be commonly affected in mercury-treated BN rats. In
      this study, we investigated the immunopathology of lupus-like oral mucosal
      lesions in a model of mercury-induced systemic autoimmunity. METHODS: Brown
      Norway male rats were injected subcutaneously with either phosphate-buffered
      saline (control) or mercury at a dose of 1.0 mg per kilogram of body weight on
      days 0, 3, 5, and 7. Blood, kidney, and tongue samples were taken at various
      timepoints for evaluation by immunohistochemistry, RT-PCR, and lupus band test
      (LBT). RESULTS: Oral mucosal lesions were classified according to three
      consecutive temporal phases on the basis of infiltration of immunocompetent cells
      as follows: (phase I) infiltration of MHC class II+ dendritic cells (DC) and
      macrophages; (phase II) addition of ED1+ macrophage infiltrates; and (phase III)
      focal infiltration of pan T cells following increased infiltration of DC and
      macrophages. Dense infiltration of DC and macrophages was observed in the
      basement membrane (BM) zone of the oral epithelium. Tissue expression of IL-4
      mRNA was detected in early lesions (phase I), suggesting that locally produced IL
      4 may be responsible for Th2-mediated immune response. A linear and continuous
      smooth pattern of fluorescence was observed in the oral epithelial BM in addition
      to renal glomeruli, indicating immune complex deposits. CONCLUSIONS: Local
      autoimmune responses are involved in the pathogenesis of mercury-induced lupus
      like lesions of the oral mucosa.

PMID- 24089705
TI  - Evaluating human cancer cell metastasis in zebrafish.
AB  - BACKGROUND: In vivo metastasis assays have traditionally been performed in mice,
      but the process is inefficient and costly. However, since zebrafish do not
      develop an adaptive immune system until 14 days post-fertilization, human cancer
      cells can survive and metastasize when transplanted into zebrafish larvae.
      Despite isolated reports, there has been no systematic evaluation of the
      robustness of this system to date. METHODS: Individual cell lines were stained
      with CM-Dil and injected into the perivitelline space of 2-day old zebrafish
      larvae. After 2-4 days fish were imaged using confocal microscopy and the number
      of metastatic cells was determined using Fiji software. RESULTS: To determine
      whether zebrafish can faithfully report metastatic potential in human cancer
      cells, we injected a series of cells with different metastatic potential into the
      perivitelline space of 2 day old embryos. Using cells from breast, prostate,
      colon and pancreas we demonstrated that the degree of cell metastasis in fish is
      proportional to their invasion potential in vitro. Highly metastatic cells such
      as MDA231, DU145, SW620 and ASPC-1 are seen in the vasculature and throughout the
      body of the fish after only 24-48 hours. Importantly, cells that are not invasive
      in vitro such as T47D, LNCaP and HT29 do not metastasize in fish. Inactivation of
      JAK1/2 in fibrosarcoma cells leads to loss of invasion in vitro and metastasis in
      vivo, and in zebrafish these cells show limited spread throughout the zebrafish
      body compared with the highly metastatic parental cells. Further, knockdown of
      WASF3 in DU145 cells which leads to loss of invasion in vitro and metastasis in
      vivo also results in suppression of metastasis in zebrafish. In a cancer
      progression model involving normal MCF10A breast epithelial cells, the degree of
      invasion/metastasis in vitro and in mice is mirrored in zebrafish. Using a
      modified version of Fiji software, it is possible to quantify individual
      metastatic cells in the transparent larvae to correlate with invasion potential.
      We also demonstrate, using lung cancers, that the zebrafish model can evaluate
      the metastatic ability of cancer cells isolated from primary tumors. CONCLUSIONS:
      The zebrafish model described here offers a rapid, robust, and inexpensive means
      of evaluating the metastatic potential of human cancer cells. Using this model it
      is possible to critically evaluate whether genetic manipulation of signaling
      pathways affects metastasis and whether primary tumors contain metastatic cells.

PMID- 24089707
TI  - Electrochemically exfoliated graphene for electrode films: effect of graphene
      flake thickness on the sheet resistance and capacitive properties.
AB  - We present an electrochemical exfoliation method to produce controlled thickness
      graphene flakes by ultrasound assistance. Bilayer graphene flakes are dominant in
      the final product by using sonication during the electrochemical exfoliation
      process, while without sonication the product contains a larger percentage of
      four-layer graphene flakes. Graphene sheets prepared by using the two procedures
      are processed into films to measure their respective sheet resistance and optical
      transmittance. Solid-state electrolyte supercapacitors are made using the two
      types of graphene films. Our study reveals that films with a higher content of
      multilayer graphene flakes are more conductive, and their resistance is more
      easily reduced by thermal annealing, making them suitable as transparent
      conducting films. The film with higher content of bilayer graphene flakes shows
      instead higher capacitance when used as electrode in a supercapacitor. 

PMID- 24089706
TI  - Entada africana fraction CH2Cl2/MEOH 5% inhibits inducible nitric oxide synthase
      and pro-inflammatory cytokines gene expression induced by lipopolysaccharide in
      microglia.
AB  - BACKGROUND: Inflammatory response in the CNS mediated by microglia cells play an
      important role in host defense and is implicated in the pathology of
      neurodegenerative diseases. We investigated the capacity of Entada africana to
      protect microglia from inflammatory insults by exploring the effect of the
      CH2Cl2/MEOH 5% fraction (Ea5) on pro-inflammatory cytokines mRNA expression.
      Finally, we studied the effect of Ea5 on the inhibition of p38 MAPK Kinase. The
      results were compared to those obtained with Baicalin, a well reported anti
      inflammatory flavonoid. METHODS: Barks from E. africana were harvested in 2010,
      in the west region of Cameroon. A crude extract was prepared using CH2Cl2/MEOH
      1:1 V/V. The crude extract obtained was further fractionated by flash
      chromatography. A mouse microglia cell line (N9) was stimulated by LPS with or
      without different concentrations of Baicalin and Ea5. The release of NO was
      evaluated using the Griess method. The expression of pro-inflammatory cytokines
      mRNA (TNFalpha, IL-1beta, IL-6) and iNOS/NO were measured by RT- PCR. The
      inhibition of p38 MAPK Kinase was assessed using ELISA. RESULTS: We found that
      Ea5, as well as Baicalin inhibited LPS-induced NO production in a dose dependent
      manner. Ea5 was most active in term of NO inhibition (87.07%), in comparison to
      Baicalin (70.85%). The expression of TNFalpha, IL-1beta, IL-6 and iNOS was
      strongly suppressed by Ea5 in microglia. Ea5 also inhibited the activity of
      p38MAPK Kinase, up to 30% for the concentrations tested, whereas a prominent
      inhibition was obtained with Baicalin. CONCLUSION: These results suggest that E.
      africana may contain promising compounds useful for the treatment of diseases
      cause by over-activation of microglia such as Alzheimer disease and other
      neurological diseases.

PMID- 24089708
TI  - Task shifting redefined: removing social and structural barriers to improve
      delivery of HIV services for people who inject drugs.
AB  - HIV infection among people who inject drugs (IDU) remains a major global public
      health challenge. However, among IDU, access to essential HIV-related services
      remains unacceptably low, especially in settings where stigma, discrimination,
      and criminalization exist. These ongoing problems account for a significant
      amount of preventable morbidity and mortality within this population, and
      indicate the need for novel approaches to HIV program delivery for IDU. Task
      shifting is a concept that has been applied successfully in African settings as a
      way to address health worker shortages. However, to date, this concept has not
      been applied as a means of addressing the social and structural barriers to HIV
      prevention and treatment experienced by IDU. Given the growing evidence
      demonstrating the effectiveness of IDU-run programs in increasing access to
      healthcare, the time has come to extend the notion of task shifting and apply it
      in settings where stigma, discrimination, and criminalization continue to pose
      significant barriers to HIV program access for IDU. By involving IDU more
      directly in the delivery of HIV programs, task shifting may serve to foster a new
      era in the response to HIV/AIDS among IDU. 

PMID- 24089709
TI  - Epinephrine for prehospital cardiac arrest with non-shockable rhythm.
AB  - Cardiopulmonary arrest research and guidelines have generally focused on the
      treatment and management of ventricular fibrillation and pulseless ventricular
      fibrillation (electrical shockable rhythms). Less investigation has been done on
      the subpopulation of cardiopulmonary arrest victims that present with non
      shockable rhythms. In a new paper, Goto, Maeda, and Goto present evidence that
      early use of epinephrine for treatment is associated with better survival with
      functional outcome. While there is a lack of evidence to support epinephrine for
      management of cardiopulmonary arrest presenting with initial shockable rhythms
      (presumed primary cardiac origin), there is now evidence that epinephrine may
      potentially benefit those presenting with non-shockable cardiopulmonary arrest
      (presumed heterogeneous origins). Further research on non-shockable rhythm
      cardiopulmonary arrest is needed to understand the subpopulation and develop
      better treatment guidelines. 

PMID- 24089710
TI  - Communication: IR spectroscopy of neutral transition metal clusters through
      thermionic emission.
AB  - The resonant multiple photon excitation of neutral niobium clusters using tunable
      infrared (IR) radiation leads to thermionic emission. By measuring the mass
      resolved ionization yield as a function of IR wavenumber species selective IR
      spectra are obtained for Nb(n) (n = 5-20) over the 200-350 cm(-1) spectral range.
      The IR resonance-enhanced multiple photon ionization spectra obtained this way
      are in good agreement with those measured using IR photodissociation of neutral
      Nb(n)-Ar clusters. An investigation of the factors determining the applicability
      of this technique identifies the internal energy threshold towards thermionic
      emission in combination with a minimum required photon flux that rapidly grows as
      a function of excitation wavelength.

PMID- 24089711
TI  - Communication: Protein dynamical transition vs. liquid-liquid phase transition in
      protein hydration water.
AB  - In this work, we compare experimental data on myoglobin hydrated powders from
      elastic neutron scattering, broadband dielectric spectroscopy, and differential
      scanning calorimetry. Our aim is to obtain new insights on the connection between
      the protein dynamical transition, a fundamental phenomenon observed in proteins
      whose physical origin is highly debated, and the liquid-liquid phase transition
      (LLPT) possibly occurring in protein hydration water and related to the existence
      of a low temperature critical point in supercooled water. Our results provide a
      consistent thermodynamic/dynamic description which gives experimental support to
      the LLPT hypothesis and further reveals how fundamental properties of water and
      proteins are tightly related.

PMID- 24089712
TI  - Perspective: Reaches of chemical physics in biology.
AB  - Chemical physics as a discipline contributes many experimental tools, algorithms,
      and fundamental theoretical models that can be applied to biological problems.
      This is especially true now as the molecular level and the systems level
      descriptions begin to connect, and multi-scale approaches are being developed to
      solve cutting edge problems in biology. In some cases, the concepts and tools got
      their start in non-biological fields, and migrated over, such as the idea of
      glassy landscapes, fluorescence spectroscopy, or master equation approaches. In
      other cases, the tools were specifically developed with biological physics
      applications in mind, such as modeling of single molecule trajectories or super
      resolution laser techniques. In this introduction to the special topic section on
      chemical physics of biological systems, we consider a wide range of
      contributions, all the way from the molecular level, to molecular assemblies,
      chemical physics of the cell, and finally systems-level approaches, based on the
      contributions to this special issue. Chemical physicists can look forward to an
      exciting future where computational tools, analytical models, and new
      instrumentation will push the boundaries of biological inquiry. 

PMID- 24089713
TI  - Structural fingerprints and their evolution during oligomeric vs. oligomer-free
      amyloid fibril growth.
AB  - Deposits of fibrils formed by disease-specific proteins are the molecular
      hallmark of such diverse human disorders as Alzheimer's disease, type II
      diabetes, or rheumatoid arthritis. Amyloid fibril formation by structurally and
      functionally unrelated proteins exhibits many generic characteristics, most
      prominently the cross beta-sheet structure of their mature fibrils. At the same
      time, amyloid formation tends to proceed along one of two separate assembly
      pathways yielding either stiff monomeric filaments or globular oligomers and
      curvilinear protofibrils. Given the focus on oligomers as major toxic species,
      the very existence of an oligomer-free assembly pathway is significant. Little is
      known, though, about the structure of the various intermediates emerging along
      different pathways and whether the pathways converge towards a common or distinct
      fibril structures. Using infrared spectroscopy we probed the structural evolution
      of intermediates and late-stage fibrils formed during in vitro lysozyme amyloid
      assembly along an oligomeric and oligomer-free pathway. Infrared spectroscopy
      confirmed that both pathways produced amyloid-specific beta-sheet peaks, but at
      pathway-specific wavenumbers. We further found that the amyloid-specific dye
      thioflavin T responded to all intermediates along either pathway. The relative
      amplitudes of thioflavin T fluorescence responses displayed pathway-specific
      differences and could be utilized for monitoring the structural evolution of
      intermediates. Pathway-specific structural features obtained from infrared
      spectroscopy and Thioflavin T responses were identical for fibrils grown at
      highly acidic or at physiological pH values and showed no discernible effects of
      protein hydrolysis. Our results suggest that late-stage fibrils formed along
      either pathway are amyloidogenic in nature, but have distinguishable structural
      fingerprints. These pathway-specific fingerprints emerge during the earliest
      aggregation events and persist throughout the entire cascade of aggregation
      intermediates formed along each pathway. 

PMID- 24089714
TI  - Catch bond-like kinetics of helix cracking: network analysis by molecular
      dynamics and milestoning.
AB  - The first events of unfolding of secondary structure under load are considered
      with Molecular Dynamics simulations and Milestoning analysis of a long helix (126
      amino acids). The Mean First Passage Time is a non-monotonic function of the
      applied load with a maximum of 3.6 ns at about 20 pN. Network analysis of the
      reaction space illustrates the opening and closing of an off-pathway trap that
      slows unfolding at intermediate load levels. It is illustrated that the nature of
      the reaction networks changes as a function of load, demonstrating that the
      process is far from one-dimensional. 

PMID- 24089715
TI  - Making novel bio-interfaces through bacterial protein recrystallization on
      biocompatible polylactide derivative films.
AB  - Fabrication of novel bio-supramolecular structures was achieved by
      recrystallizing the bacterial surface protein SbpA on amorphous and
      semicrystalline polylactide derivatives. Differential scanning calorimetry showed
      that the glass transition temperature (T(g)) for (poly-L-lactide)-PLLA, poly(L,D
      lactide)-PDLLA, poly(lactide-co-glycolide)-PLGA and poly(lactide-co-caprolactone)
      PLCL was 63  degrees C, 53  degrees C, 49  degrees C and 15  degrees C,
      respectively. Tensile stress-strain tests indicated that PLLA, PLGA, and PDLLA
      had a glassy behaviour when tested below T(g). The obtained Young modulus were
      1477 MPa, 1330 MPa, 1306 MPa, and 9.55 MPa for PLLA, PLGA, PDLLA, and PLCL,
      respectively. Atomic force microscopy results confirmed that SbpA recrystallized
      on every polymer substrate exhibiting the native S-layer P4 lattice (a = b = 13
      nm, gamma = 90 degrees ). However, the polymer substrate influenced the domain
      size of the S-protein crystal, with the smallest size for PLLA (0.011 MUm(2)),
      followed by PDLLA (0.034 MUm(2)), and PLGA (0.039 MUm(2)), and the largest size
      for PLCL (0.09 MUm(2)). quartz crystal microbalance with dissipation monitoring
      (QCM-D) measurements indicated that the adsorbed protein mass per unit area
      (~1800 ng cm(-2)) was independent of the mechanical, thermal, and crystalline
      properties of the polymer support. The slowest protein adsorption rate was
      observed for amorphous PLCL (the polymer with the weakest mechanical properties
      and lowest T(g)). QCM-D also monitored protein self-assembly in solution and
      confirmed that S-layer formation takes place in three main steps: adsorption,
      self-assembly, and crystal reorganization. Finally, this work shows that
      biodegradable polylactide derivatives films are a suitable support to form robust
      biomimetic S-protein layers.

PMID- 24089716
TI  - Phase transitions in human IgG solutions.
AB  - Protein condensations, such as crystallization, liquid-liquid phase separation,
      aggregation, and gelation, have been observed in concentrated antibody solutions
      under various solution conditions. While most IgG antibodies are quite soluble, a
      few outliers can undergo condensation under physiological conditions.
      Condensation of IgGs can cause serious consequences in some human diseases and in
      biopharmaceutical formulations. The phase transitions underlying protein
      condensations in concentrated IgG solutions is also of fundamental interest for
      the understanding of the phase behavior of non-spherical protein molecules. Due
      to the high solubility of generic IgGs, the phase behavior of IgG solutions has
      not yet been well studied. In this work, we present an experimental approach to
      study IgG solutions in which the phase transitions are hidden below the freezing
      point of the solution. Using this method, we have investigated liquid-liquid
      phase separation of six human myeloma IgGs and two recombinant pharmaceutical
      human IgGs. We have also studied the relation between crystallization and liquid
      liquid phase separation of two human cryoglobulin IgGs. Our experimental results
      reveal several important features of the generic phase behavior of IgG solutions:
      (1) the shape of the coexistence curve is similar for all IgGs but quite
      different from that of quasi-spherical proteins; (2) all IgGs have critical
      points located at roughly the same protein concentration at ~100 mg/ml while
      their critical temperatures vary significantly; and (3) the liquid-liquid phase
      separation in IgG solutions is metastable with respect to crystallization. These
      features of phase behavior of IgG solutions reflect the fact that all IgGs have
      nearly identical molecular geometry but quite diverse net inter-protein
      interaction energies. This work provides a foundation for further experimental
      and theoretical studies of the phase behavior of generic IgGs as well as outliers
      with large propensity to condense. The investigation of the phase diagram of IgG
      solutions is of great importance for the understanding of immunoglobulin
      deposition diseases as well as for the understanding of the colloidal stability
      of IgG pharmaceutical formulations.

PMID- 24089717
TI  - Quantitative comparison of alternative methods for coarse-graining biological
      networks.
AB  - Markov models and master equations are a powerful means of modeling dynamic
      processes like protein conformational changes. However, these models are often
      difficult to understand because of the enormous number of components and
      connections between them. Therefore, a variety of methods have been developed to
      facilitate understanding by coarse-graining these complex models. Here, we employ
      Bayesian model comparison to determine which of these coarse-graining methods
      provides the models that are most faithful to the original set of states. We find
      that the Bayesian agglomerative clustering engine and the hierarchical Nystrom
      expansion graph (HNEG) typically provide the best performance. Surprisingly, the
      original Perron cluster cluster analysis (PCCA) method often provides the next
      best results, outperforming the newer PCCA+ method and the most probable paths
      algorithm. We also show that the differences between the models are qualitatively
      significant, rather than being minor shifts in the boundaries between states. The
      performance of the methods correlates well with the entropy of the resulting
      coarse-grainings, suggesting that finding states with more similar populations
      (i.e., avoiding low population states that may just be noise) gives better
      results.

PMID- 24089718
TI  - Fitting coarse-grained distribution functions through an iterative force-matching
      method.
AB  - An iterative coarse-graining method is developed for systematically converting an
      atomistic force field to a model at lower resolution that is able to accurately
      reproduce the distribution functions defined in the coarse-grained potential. The
      method starts from the multiscale coarse-graining (MS-CG) approach, and it
      iteratively refines the distribution functions using repeated applications of the
      MS-CG algorithm. It is justified on the basis of the force matching normal
      equation, which can be considered a discrete form of the Yvon-Born-Green equation
      in liquid state theory. Numerical results for molecular systems involving
      pairwise nonbonded and three-body bonded interactions are obtained, and
      comparison with other approaches in literature is provided. 

PMID- 24089719
TI  - A quantitative measure for protein conformational heterogeneity.
AB  - Conformational heterogeneity is a defining characteristic of proteins.
      Intrinsically disordered proteins (IDPs) and denatured state ensembles are
      extreme manifestations of this heterogeneity. Inferences regarding globule versus
      coil formation can be drawn from analysis of polymeric properties such as average
      size, shape, and density fluctuations. Here we introduce a new parameter to
      quantify the degree of conformational heterogeneity within an ensemble to
      complement polymeric descriptors. The design of this parameter is guided by the
      need to distinguish between systems that couple their unfolding-folding
      transitions with coil-to-globule transitions and those systems that undergo coil
      to-globule transitions with no evidence of acquiring a homogeneous ensemble of
      conformations upon collapse. The approach is as follows: Each conformation in an
      ensemble is converted into a conformational vector where the elements are inter
      residue distances. Similarity between pairs of conformations is quantified using
      the projection between the corresponding conformational vectors. An ensemble of
      conformations yields a distribution of pairwise projections, which is converted
      into a distribution of pairwise conformational dissimilarities. The first moment
      of this dissimilarity distribution is normalized against the first moment of the
      distribution obtained by comparing conformations from the ensemble of interest to
      conformations drawn from a Flory random coil model. The latter sets an upper
      bound on conformational heterogeneity thus ensuring that the proposed measure for
      intra-ensemble heterogeneity is properly calibrated and can be used to compare
      ensembles for different sequences and across different temperatures. The new
      measure of conformational heterogeneity will be useful in quantitative studies of
      coupled folding and binding of IDPs and in de novo sequence design efforts that
      are geared toward controlling the degree of heterogeneity in unbound forms of
      IDPs. 

PMID- 24089721
TI  - Energy landscapes and global thermodynamics for alanine peptides.
AB  - We compare different approaches for computing the thermodynamics of biomolecular
      systems. Techniques based on parallel replicas evolving via molecular dynamics or
      Monte Carlo simulations produce overlapping histograms for the densities of
      states. In contrast, energy landscape methods employ a superposition partition
      function constructed from local minima of the potential energy surface. The
      latter approach is particularly powerful for systems exhibiting broken
      ergodicity, and it is usually implemented using a harmonic normal mode
      approximation, which has not been extensively tested for biomolecules. The
      present contribution compares these alternative approaches for small alanine
      peptides modelled using the CHARMM and AMBER force fields. Densities of states
      produced from canonical sampling using multiple temperature replicas provide
      accurate reference data to evaluate the effect of the harmonic normal mode
      approximation in the superposition calculations. This benchmarking lays
      foundations for the application of energy landscape methods to larger
      biomolecules. It will also provide well characterised model systems for
      developing enhanced sampling methods, and for the treatment of anharmonicity
      corresponding to individual local minima. 

PMID- 24089720
TI  - Funneling and frustration in the energy landscapes of some designed and
      simplified proteins.
AB  - We explore the similarities and differences between the energy landscapes of
      proteins that have been selected by nature and those of some proteins designed by
      humans. Natural proteins have evolved to function as well as fold, and this is a
      source of energetic frustration. The sequence of Top7, on the other hand, was
      designed with architecture alone in mind using only native state stability as the
      optimization criterion. Its topology had not previously been observed in nature.
      Experimental studies show that the folding kinetics of Top7 is more complex than
      the kinetics of folding of otherwise comparable naturally occurring proteins. In
      this paper, we use structure prediction tools, frustration analysis, and free
      energy profiles to illustrate the folding landscapes of Top7 and two other
      proteins designed by Takada. We use both perfectly funneled (structure-based) and
      predictive (transferable) models to gain insight into the role of topological
      versus energetic frustration in these systems and show how they differ from those
      found for natural proteins. We also study how robust the folding of these designs
      would be to the simplification of the sequences using fewer amino acid types.
      Simplification using a five amino acid type code results in comparable quality of
      structure prediction to the full sequence in some cases, while the two-letter
      simplification scheme dramatically reduces the quality of structure prediction. 

PMID- 24089722
TI  - Effect of ligand diffusion on occupancy fluctuations of cell-surface receptors.
AB  - The role of diffusion in the kinetics of reversible ligand binding to receptors
      on a cell surface or to a macromolecule with multiple binding sites is
      considered. A formalism is developed that is based on a Markovian master equation
      for the distribution function of the number of occupied receptors containing rate
      constants that depend on the ligand diffusivity. The formalism is used to derive
      (1) a nonlinear rate equation for the mean number of occupied receptors and (2)
      an analytical expression for the relaxation time that characterizes the decay of
      equilibrium fluctuations of the occupancy of the receptors. The relaxation time
      is shown to depend on the ligand diffusivity and concentration, the number of
      receptors, the cell radius, and intrinsic association/dissociation rate
      constants. This result is then used to estimate the accuracy of the ligand
      concentration measurements by the cell, which, according to the Berg-Purcell
      model, is related to fluctuations in the receptor occupancy, averaged over a
      finite interval of time. Specifically, a simple expression (which is exact in the
      framework of our formalism) is derived for the variance in the measured ligand
      concentration in the limit of long averaging times.

PMID- 24089723
TI  - Hematin crystallization from aqueous and organic solvents.
AB  - Hematin crystallization is the main mechanism of detoxification of heme that is
      released in malaria-infected erythrocytes as a byproduct of the hemoglobin
      catabolism by the parasite. A controversy exists over whether hematin crystals
      grow from the aqueous medium of the parasite's digestive vacuole or in the lipid
      bodies present in the vacuole. To this end, we compare the basic thermodynamic
      and structural features of hematin crystallization in an aqueous buffer at pH
      4.8, as in the digestive vacuole, and in water-saturated octanol that mimics the
      environment of the lipid nanospheres. We show that in aqueous solutions, hematin
      aggregation into mesoscopic disordered clusters is insignificant. We determine
      the solubility of the beta-hematin crystals in the pH range 4.8-7.6. We image by
      atomic force microscopy crystals grown at pH 4.8 and show that their macroscopic
      and mesoscopic morphology features are incompatible with those reported for
      biological hemozoin. In contrast, crystals grown in the presence of octanol are
      very similar to those extracted from parasites. We determine the hematin
      solubility in water-saturated octanol at three temperatures. These solubilities
      are four orders of magnitude higher than that at pH 4.8, providing for faster
      crystallization from organic than from aqueous solvents. These observations
      further suggest that the lipid bodies play a role in mediating biological
      hemozoin crystal growth to ensure faster heme detoxification. 

PMID- 24089725
TI  - Order statistics inference for describing topological coupling and mechanical
      symmetry breaking in multidomain proteins.
AB  - Cooperativity is a hallmark of proteins, many of which show a modular
      architecture comprising discrete structural domains. Detecting and describing
      dynamic couplings between structural regions is difficult in view of the many
      body nature of protein-protein interactions. By utilizing the GPU-based
      computational acceleration, we carried out simulations of the protein forced
      unfolding for the dimer WW - WW of the all-beta-sheet WW domains used as a model
      multidomain protein. We found that while the physically non-interacting identical
      protein domains (WW) show nearly symmetric mechanical properties at low tension,
      reflected, e.g., in the similarity of their distributions of unfolding times,
      these properties become distinctly different when tension is increased. Moreover,
      the uncorrelated unfolding transitions at a low pulling force become increasingly
      more correlated (dependent) at higher forces. Hence, the applied force not only
      breaks "the mechanical symmetry" but also couples the physically non-interacting
      protein domains forming a multi-domain protein. We call this effect "the
      topological coupling." We developed a new theory, inspired by order statistics,
      to characterize protein-protein interactions in multi-domain proteins. The method
      utilizes the squared-Gaussian model, but it can also be used in conjunction with
      other parametric models for the distribution of unfolding times. The formalism
      can be taken to the single-molecule experimental lab to probe mechanical
      cooperativity and domain communication in multi-domain proteins. 

PMID- 24089724
TI  - Global motions exhibited by proteins in micro- to milliseconds simulations concur
      with anisotropic network model predictions.
AB  - The Anton supercomputing technology recently developed for efficient molecular
      dynamics simulations permits us to examine micro- to milli-second events at full
      atomic resolution for proteins in explicit water and lipid bilayer. It also
      permits us to investigate to what extent the collective motions predicted by
      network models (that have found broad use in molecular biophysics) agree with
      those exhibited by full-atomic long simulations. The present study focuses on
      Anton trajectories generated for two systems: the bovine pancreatic trypsin
      inhibitor, and an archaeal aspartate transporter, GltPh. The former, a thoroughly
      studied system, helps benchmark the method of comparative analysis, and the
      latter provides new insights into the mechanism of function of glutamate
      transporters. The principal modes of motion derived from both simulations closely
      overlap with those predicted for each system by the anisotropic network model
      (ANM). Notably, the ANM modes define the collective mechanisms, or the pathways
      on conformational energy landscape, that underlie the passage between the crystal
      structure and substates visited in simulations. In particular, the lowest
      frequency ANM modes facilitate the conversion between the most probable
      substates, lending support to the view that easy access to functional substates
      is a robust determinant of evolutionarily selected native contact topology. 

PMID- 24089727
TI  - Competition enhances stochasticity in biochemical reactions.
AB  - We study stochastic dynamics of two competing complexation reactions (i) A + B<
      >AB and (ii) A + C<->AC. Such reactions are common in biology where different
      reactants compete for common resources--examples range from binding enzyme
      kinetics to gene expression. On the other hand, stochasticity is inherent in
      biological systems due to small copy numbers. We investigate the complex
      interplay between competition and stochasticity, using coupled complexation
      reactions as the model system. Within the master equation formalism, we compute
      the exact distribution of the number of complexes to analyze equilibrium
      fluctuations of several observables. Our study reveals that the presence of
      competition offered by one reaction (say A + C<->AC) can significantly enhance
      the fluctuation in the other (A + B<->AB). We provide detailed quantitative
      estimates of this enhanced fluctuation for different combinations of rate
      constants and numbers of reactant molecules that are typical in biology. We
      notice that fluctuations can be significant even when two of the reactant
      molecules (say B and C) are infinite in number, maintaining a fixed
      stoichiometry, while the other reactant (A) is finite. This is purely due to the
      coupling mediated via resource sharing and is in stark contrast to the single
      reaction scenario, where large numbers of one of the components ensure zero
      fluctuation. Our detailed analysis further highlights regions where numerical
      estimates of mass action solutions can differ from the actual averages. These
      observations indicate that averages can be a poor representation of the system,
      hence analysis that is purely based on averages such as mass action laws can be
      potentially misleading in such noisy biological systems. We believe that the
      exhaustive study presented here will provide qualitative and quantitative
      insights into the role of noise and its enhancement in the presence of
      competition that will be relevant in many biological settings.

PMID- 24089728
TI  - Noisy continuous time random walks.
AB  - Experimental studies of the diffusion of biomolecules within biological cells are
      routinely confronted with multiple sources of stochasticity, whose identification
      renders the detailed data analysis of single molecule trajectories quite
      intricate. Here, we consider subdiffusive continuous time random walks that
      represent a seminal model for the anomalous diffusion of tracer particles in
      complex environments. This motion is characterized by multiple trapping events
      with infinite mean sojourn time. In real physical situations, however, instead of
      the full immobilization predicted by the continuous time random walk model, the
      motion of the tracer particle shows additional jiggling, for instance, due to
      thermal agitation of the environment. We here present and analyze in detail an
      extension of the continuous time random walk model. Superimposing the multiple
      trapping behavior with additive Gaussian noise of variable strength, we
      demonstrate that the resulting process exhibits a rich variety of apparent
      dynamic regimes. In particular, such noisy continuous time random walks may
      appear ergodic, while the bare continuous time random walk exhibits weak
      ergodicity breaking. Detailed knowledge of this behavior will be useful for the
      truthful physical analysis of experimentally observed subdiffusion. 

PMID- 24089726
TI  - Electrostatic origin of in vitro aggregation of human gamma-crystallin.
AB  - The proteins alpha-, beta-, and gamma-crystallins are the major components of the
      lens in the human eye. Using dynamic light scattering method, we have performed
      in vitro investigations of protein-protein interactions in dilute solutions of
      human gamma-crystallin and alpha-crystallin. We find that gamma-crystallin
      spontaneously aggregates into finite-sized clusters in phosphate buffer
      solutions. There are two distinct populations of unaggregated and aggregated
      gamma-crystallins in these solutions. On the other hand, alpha-crystallin
      molecules are not aggregated into large clusters in solutions of alpha-crystallin
      alone. When alpha-crystallin and gamma-crystallin are mixed in phosphate buffer
      solutions, we demonstrate that the clusters of gamma-crystallin are prevented. By
      further investigating the roles of temperature, protein concentration, pH, salt
      concentration, and a reducing agent, we show that the aggregation of gamma
      crystallin under our in vitro conditions arises from non-covalent electrostatic
      interactions. In addition, we show that aggregation of gamma-crystallin occurs
      under the dilute in vitro conditions even in the absence of oxidizing agents that
      can induce disulfide cross-links, long considered to be responsible for human
      cataracts. Aggregation of gamma-crystallin when maintained under reducing
      conditions suggests that oxidation does not contribute to the aggregation in
      dilute solutions. 

PMID- 24089729
TI  - Inclusion of persistence length-based secondary structure in replica field
      theoretic models of heteropolymer freezing.
AB  - The protein folding problem has long represented a "holy grail" in statistical
      physics due to its physical complexity and its relevance to many human diseases.
      While past theoretical work has yielded apt descriptions of protein folding
      landscapes, recent large-scale simulations have provided insights into protein
      folding that were impractical to obtain from early theories. In particular, the
      role that non-native contacts play in protein folding, and their relation to the
      existence of misfolded, beta-sheet rich trap states on folding landscapes, has
      emerged as a topic of interest in the field. In this paper, we present a modified
      model of heteropolymer freezing that includes explicit secondary structural
      characteristics which allow observations of "intramolecular amyloid" states to be
      probed from a theoretical perspective. We introduce a variable persistence length
      based energy penalty to a model Hamiltonian, and we illustrate how this
      modification alters the phase transitions present in the theory. We find, in
      particular, that inclusion of this variable persistence length increases both
      generic freezing and folding temperatures in the model, allowing both folding and
      glass transitions to occur in a more highly optimized fashion. We go on to
      discuss how these changes might relate to protein evolution, misfolding, and the
      emergence of intramolecular amyloid states. 

PMID- 24089730
TI  - Combinatoric analysis of heterogeneous stochastic self-assembly.
AB  - We analyze a fully stochastic model of heterogeneous nucleation and self-assembly
      in a closed system with a fixed total particle number M, and a fixed number of
      seeds Ns. Each seed can bind a maximum of N particles. A discrete master equation
      for the probability distribution of the cluster sizes is derived and the
      corresponding cluster concentrations are found using kinetic Monte-Carlo
      simulations in terms of the density of seeds, the total mass, and the maximum
      cluster size. In the limit of slow detachment, we also find new analytic
      expressions and recursion relations for the cluster densities at intermediate
      times and at equilibrium. Our analytic and numerical findings are compared with
      those obtained from classical mass-action equations and the discrepancies between
      the two approaches analyzed. 

PMID- 24089732
TI  - Potential and flux field landscape theory. I. Global stability and dynamics of
      spatially dependent non-equilibrium systems.
AB  - We established a potential and flux field landscape theory to quantify the global
      stability and dynamics of general spatially dependent non-equilibrium
      deterministic and stochastic systems. We extended our potential and flux
      landscape theory for spatially independent non-equilibrium stochastic systems
      described by Fokker-Planck equations to spatially dependent stochastic systems
      governed by general functional Fokker-Planck equations as well as functional
      Kramers-Moyal equations derived from master equations. Our general theory is
      applied to reaction-diffusion systems. For equilibrium spatially dependent
      systems with detailed balance, the potential field landscape alone, defined in
      terms of the steady state probability distribution functional, determines the
      global stability and dynamics of the system. The global stability of the system
      is closely related to the topography of the potential field landscape in terms of
      the basins of attraction and barrier heights in the field configuration state
      space. The effective driving force of the system is generated by the functional
      gradient of the potential field alone. For non-equilibrium spatially dependent
      systems, the curl probability flux field is indispensable in breaking detailed
      balance and creating non-equilibrium condition for the system. A complete
      characterization of the non-equilibrium dynamics of the spatially dependent
      system requires both the potential field and the curl probability flux field.
      While the non-equilibrium potential field landscape attracts the system down
      along the functional gradient similar to an electron moving in an electric field,
      the non-equilibrium flux field drives the system in a curly way similar to an
      electron moving in a magnetic field. In the small fluctuation limit, the
      intrinsic potential field as the small fluctuation limit of the potential field
      for spatially dependent non-equilibrium systems, which is closely related to the
      steady state probability distribution functional, is found to be a Lyapunov
      functional of the deterministic spatially dependent system. Therefore, the
      intrinsic potential landscape can characterize the global stability of the
      deterministic system. The relative entropy functional of the stochastic spatially
      dependent non-equilibrium system is found to be the Lyapunov functional of the
      stochastic dynamics of the system. Therefore, the relative entropy functional
      quantifies the global stability of the stochastic system with finite
      fluctuations. Our theory offers an alternative general approach to other field
      theoretic techniques, to study the global stability and dynamics of spatially
      dependent non-equilibrium field systems. It can be applied to many physical,
      chemical, and biological spatially dependent non-equilibrium systems. 

PMID- 24089731
TI  - Simulating movement of tRNA through the ribosome during hybrid-state formation.
AB  - Biomolecular simulations provide a means for exploring the relationship between
      flexibility, energetics, structure, and function. With the availability of atomic
      models from X-ray crystallography and cryoelectron microscopy (cryo-EM), and
      rapid increases in computing capacity, it is now possible to apply molecular
      dynamics (MD) simulations to large biomolecular machines, and systematically
      partition the factors that contribute to function. A large biomolecular complex
      for which atomic models are available is the ribosome. In the cell, the ribosome
      reads messenger RNA (mRNA) in order to synthesize proteins. During this essential
      process, the ribosome undergoes a wide range of conformational rearrangements.
      One of the most poorly understood transitions is translocation: the process by
      which transfer RNA (tRNA) molecules move between binding sites inside of the
      ribosome. The first step of translocation is the adoption of a "hybrid"
      configuration by the tRNAs, which is accompanied by large-scale rotations in the
      ribosomal subunits. To illuminate the relationship between these rearrangements,
      we apply MD simulations using a multi-basin structure-based (SMOG) model,
      together with targeted molecular dynamics protocols. From 120 simulated
      transitions, we demonstrate the viability of a particular route during P/E hybrid
      state formation, where there is asynchronous movement along rotation and tRNA
      coordinates. These simulations not only suggest an ordering of events, but they
      highlight atomic interactions that may influence the kinetics of hybrid-state
      formation. From these simulations, we also identify steric features (H74 and
      surrounding residues) encountered during the hybrid transition, and observe that
      flexibility of the single-stranded 3'-CCA tail is essential for it to reach the
      endpoint. Together, these simulations provide a set of structural and energetic
      signatures that suggest strategies for modulating the physical-chemical
      properties of protein synthesis by the ribosome.

PMID- 24089733
TI  - Asymmetric processing of a substrate protein in sequential allosteric cycles of
      AAA+ nanomachines.
AB  - Essential protein quality control includes mechanisms of substrate protein (SP)
      unfolding and translocation performed by powerful ring-shaped AAA+ (ATPases
      associated with various cellular activities) nanomachines. These SP remodeling
      actions are effected by mechanical forces imparted by AAA+ loops that protrude
      into the central channel. Sequential intra-ring allosteric motions, which
      underlie repetitive SP-loop interactions, have been proposed to comprise
      clockwise (CW), counterclockwise (CCW), or random (R) conformational transitions
      of individual AAA+ subunits. To probe the effect of these allosteric mechanisms
      on unfoldase and translocase functions, we perform Langevin dynamics simulations
      of a coarse-grained model of an all-alpha SP processed by the single-ring ClpY
      ATPase or by the double-ring p97 ATPase. We find that, in all three allosteric
      mechanisms, the SP undergoes conformational transitions along a common set of
      pathways, which reveals that the active work provided by the ClpY machine
      involves single loop-SP interactions. Nevertheless, the rates and yields of SP
      unfolding and translocation are controlled by mechanism-dependent loop-SP binding
      events, as illustrated by faster timescales of SP processing in CW allostery
      compared with CCW and R allostery. The distinct efficacy of allosteric mechanisms
      is due to the asymmetric collaboration of adjacent subunits, which involves CW
      biased structural motions of AAA+ loops and results in CW-compatible torque
      applied onto the SP. Additional simulations of mutant ClpY rings, which render a
      subset of subunits catalytically-defective or reduce their SP binding affinity,
      reveal that subunit-based conformational transitions play the major role in SP
      remodeling. Based on these results we predict that the minimally functional AAA+
      ring includes three active subunits, only two of which are adjacent. 

PMID- 24089734
TI  - Dynamic simulation of concentrated macromolecular solutions with screened long
      range hydrodynamic interactions: algorithm and limitations.
AB  - Hydrodynamic interactions exert a critical effect on the dynamics of
      macromolecules. As the concentration of macromolecules increases, by analogy to
      the behavior of semidilute polymer solutions or the flow in porous media, one
      might expect hydrodynamic screening to occur. Hydrodynamic screening would have
      implications both for the understanding of macromolecular dynamics as well as
      practical implications for the simulation of concentrated macromolecular
      solutions, e.g., in cells. Stokesian dynamics (SD) is one of the most accurate
      methods for simulating the motions of N particles suspended in a viscous fluid at
      low Reynolds number, in that it considers both far-field and near-field
      hydrodynamic interactions. This algorithm traditionally involves an O(N(3))
      operation to compute Brownian forces at each time step, although asymptotically
      faster but more complex SD methods are now available. Motivated by the idea of
      hydrodynamic screening, the far-field part of the hydrodynamic matrix in SD may
      be approximated by a diagonal matrix, which is equivalent to assuming that long
      range hydrodynamic interactions are completely screened. This approximation
      allows sparse matrix methods to be used, which can reduce the apparent
      computational scaling to O(N). Previously there were several simulation studies
      using this approximation for monodisperse suspensions. Here, we employ newly
      designed preconditioned iterative methods for both the computation of Brownian
      forces and the solution of linear systems, and consider the validity of this
      approximation in polydisperse suspensions. We evaluate the accuracy of the
      diagonal approximation method using an intracellular-like suspension. The
      diffusivities of particles obtained with this approximation are close to those
      with the original method. However, this approximation underestimates
      intermolecular correlated motions, which is a trade-off between accuracy and
      computing efficiency. The new method makes it possible to perform large-scale and
      long-time simulation with an approximate accounting of hydrodynamic interactions.

PMID- 24089735
TI  - Statistical physics of self-replication.
AB  - Self-replication is a capacity common to every species of living thing, and
      simple physical intuition dictates that such a process must invariably be fueled
      by the production of entropy. Here, we undertake to make this intuition rigorous
      and quantitative by deriving a lower bound for the amount of heat that is
      produced during a process of self-replication in a system coupled to a thermal
      bath. We find that the minimum value for the physically allowed rate of heat
      production is determined by the growth rate, internal entropy, and durability of
      the replicator, and we discuss the implications of this finding for bacterial
      cell division, as well as for the pre-biotic emergence of self-replicating
      nucleic acids. 

PMID- 24089736
TI  - Generalized iterative annealing model for the action of RNA chaperones.
AB  - As a consequence of the rugged landscape of RNA molecules their folding is
      described by the kinetic partitioning mechanism according to which only a small
      fraction (phiF) reaches the folded state while the remaining fraction of
      molecules is kinetically trapped in misfolded intermediates. The transition from
      the misfolded states to the native state can far exceed biologically relevant
      time. Thus, RNA folding in vivo is often aided by protein cofactors, called RNA
      chaperones, that can rescue RNAs from a multitude of misfolded structures. We
      consider two models, based on chemical kinetics and chemical master equation, for
      describing assisted folding. In the passive model, applicable for class I
      substrates, transient interactions of misfolded structures with RNA chaperones
      alone are sufficient to destabilize the misfolded structures, thus entropically
      lowering the barrier to folding. For this mechanism to be efficient the
      intermediate ribonucleoprotein complex between collapsed RNA and protein cofactor
      should have optimal stability. We also introduce an active model (suitable for
      stringent substrates with small phiF), which accounts for the recent experimental
      findings on the action of CYT-19 on the group I intron ribozyme, showing that RNA
      chaperones do not discriminate between the misfolded and the native states. In
      the active model, the RNA chaperone system utilizes chemical energy of adenosine
      triphosphate hydrolysis to repeatedly bind and release misfolded and folded RNAs,
      resulting in substantial increase of yield of the native state. The theory
      outlined here shows, in accord with experiments, that in the steady state the
      native state does not form with unit probability. 

PMID- 24089737
TI  - Unfolded protein ensembles, folding trajectories, and refolding rate prediction.
AB  - Computer simulations can provide critical information on the unfolded ensemble of
      proteins under physiological conditions, by explicitly characterizing the
      geometrical properties of the diverse conformations that are sampled in the
      unfolded state. A general computational analysis across many proteins has not
      been implemented however. Here, we develop a method for generating a diverse
      conformational ensemble, to characterize properties of the unfolded states of
      intrinsically disordered or intrinsically folded proteins. The method allows
      unfolded proteins to retain disulfide bonds. We examined physical properties of
      the unfolded ensembles of several proteins, including chemical shifts, clustering
      properties, and scaling exponents for the radius of gyration with polymer length.
      A problem relating simulated and experimental residual dipolar couplings is
      discussed. We apply our generated ensembles to the problem of folding kinetics,
      by examining whether the ensembles of some proteins are closer geometrically to
      their folded structures than others. We find that for a randomly selected dataset
      of 15 non-homologous 2- and 3-state proteins, quantities such as the average root
      mean squared deviation between the folded structure and unfolded ensemble
      correlate with folding rates as strongly as absolute contact order. We introduce
      a new order parameter that measures the distance travelled per residue, which
      naturally partitions into a smooth "laminar" and subsequent "turbulent" part of
      the trajectory. This latter conceptually simple measure with no fitting
      parameters predicts folding rates in 0 M denaturant with remarkable accuracy (r =
      -0.95, p = 1 * 10(-7)). The high correlation between folding times and sterically
      modulated, reconfigurational motion supports the rapid collapse of proteins prior
      to the transition state as a generic feature in the folding of both two-state and
      multi-state proteins. This method for generating unfolded ensembles provides a
      powerful approach to address various questions in protein evolution, misfolding
      and aggregation, transient structures, and molten globule and disordered protein
      phases. 

PMID- 24089738
TI  - Mechanics of severing for large microtubule complexes revealed by coarse-grained
      simulations.
AB  - We investigate the mechanical behavior of microtubule (MT) protofilaments under
      the action of bending forces, ramped up linearly in time, to provide insight into
      the severing of MTs by microtubule associated proteins (MAPs). We used the self
      organized polymer model which employs a coarse-grained description of the protein
      chain and ran Brownian dynamics simulations accelerated on graphics processing
      units that allow us to follow the dynamics of a MT system on experimental
      timescales. Our study focused on the role played in the MT depolymerization
      dynamics by the inter-tubulin contacts a protofilament experiences when embedded
      in the MT lattice, and the number of binding sites of MAPs on MTs. We found that
      proteins inducing breaking of MTs must have at least three attachment points on
      any tubulin dimer from an isolated protofilament. In contrast, two points of
      contact would suffice when dimers are located in an intact MT lattice, in accord
      with experimental findings on MT severing proteins. Our results show that
      confinement of a protofilament in the MT lattice leads to a drastic reduction in
      the energy required for the removal of tubulin dimers, due to the drastic
      reduction in entropy. We further showed that there are differences in the
      energetic requirements based on the location of the dimer to be removed by
      severing. Comparing the energy of tubulin dimers removal revealed by our
      simulations with the amount of energy resulting from one ATP hydrolysis, which is
      the source of energy for all MAPs, we provided strong evidence for the
      experimental finding that severing proteins do not bind uniformly along the MT
      wall. 

PMID- 24089739
TI  - Global analysis of ion dependence unveils hidden steps in DNA binding and bending
      by integration host factor.
AB  - Proteins that recognize and bind to specific sites on DNA often distort the DNA
      at these sites. The rates at which these DNA distortions occur are considered to
      be important in the ability of these proteins to discriminate between specific
      and nonspecific sites. These rates have proven difficult to measure for most
      protein-DNA complexes in part because of the difficulty in separating the
      kinetics of unimolecular conformational rearrangements (DNA bending and kinking)
      from the kinetics of bimolecular complex association and dissociation. A notable
      exception is the Integration Host Factor (IHF), a eubacterial architectural
      protein involved in chromosomal compaction and DNA recombination, which binds
      with subnanomolar affinity to specific DNA sites and bends them into sharp U
      turns. The unimolecular DNA bending kinetics has been resolved using both stopped
      flow and laser temperature-jump perturbation. Here we expand our investigation by
      presenting a global analysis of the ionic strength dependence of specific binding
      affinity and relaxation kinetics of an IHF-DNA complex. This analysis enables us
      to obtain each of the underlying elementary rates (DNA bending/unbending and
      protein-DNA association/dissociation), and their ionic strength dependence, even
      under conditions where the two processes are coupled. Our analysis indicates
      interesting differences in the ionic strength dependence of the bi- versus
      unimolecular steps. At moderate [KCl] (100-500 mM), nearly all the ionic strength
      dependence to the overall equilibrium binding affinity appears in the bimolecular
      association/dissociation of an initial, presumably weakly bent, encounter
      complex, with a slope SK(bi) ~ 8 describing the loglog-dependence of the
      equilibrium constant to form this complex on [KCl]. In contrast, the unimolecular
      equilibrium constant to form the fully wrapped specific complex from the initial
      complex is nearly independent of [KCl], with SK(uni) < 0.5. This result is
      counterintuitive because there are at least twice as many ionic protein-DNA
      contacts in the fully wrapped complex than in the weakly bent intermediate. The
      following picture emerges from this analysis: in the bimolecular step, the
      observed [KCl]-dependence is consistent with the number of DNA counterions
      expected to be released when IHF binds nonspecifically to DNA whereas in the
      unimolecular reorganization step, the weak [KCl]-dependence suggests that two
      effects cancel one another. On one hand, formation of additional protein-DNA
      contacts in the fully wrapped complex releases bound counterions into bulk
      solution, which is entropically favored by decreasing [salt]. On the other hand,
      formation of the fully wrapped complex also releases tightly bound water
      molecules, which is osmotically favored by increasing [salt]. More generally, our
      global analysis strategy is applicable to other protein-DNA complexes, and opens
      up the possibility of measuring DNA bending rates in complexes where the
      unimolecular and bimolecular steps are not easily separable.

PMID- 24089740
TI  - Micellization model for the polymerization of clathrin baskets.
AB  - A thermodynamic model is used to investigate the conditions under which clathrin
      triskelions form polyhedral baskets. The analysis, which is similar to classical
      methods used to study micelle formation, relates clathrin basket energetics to
      system parameters linked to triskelial rigidity, the natural curvature of an
      isolated triskelion, and interactions between triskelial legs in the assembled
      polyhedra. Mathematical theory predicts that a minimal ("critical") clathrin
      concentration, C(C), needs to be surpassed in order for basket polymerization to
      occur, and indicates how C(C), and the amount of polymerized material, depend on
      the chosen parameters. Analytical expressions are obtained to indicate how
      changes in the parameters affect the sizes of the polyhedra which arise when the
      total clathrin concentration exceeds C(C). A continuum analytic approximation
      then is used to produce numerical results that illustrate the derived
      dependences.

PMID- 24089742
TI  - Single-molecule spectroscopy of the unexpected collapse of an unfolded protein at
      low pH.
AB  - The dimensions of intrinsically disordered and unfolded proteins critically
      depend on the solution conditions, such as temperature, pH, ionic strength, and
      osmolyte or denarurant concentration. However, a quantitative understanding of
      how the complex combination of chain-chain and chain-solvent interactions is
      affected by the solvent is still missing. Here, we take a step towards this goal
      by investigating the combined effect of pH and denaturants on the dimensions of
      an unfolded protein. We use single-molecule fluorescence spectroscopy to extract
      the dimensions of unfolded cold shock protein (CspTm) in mixtures of the
      denaturants urea and guanidinium chloride (GdmCl) at neutral and acidic pH.
      Surprisingly, even though a change in pH from 7 to 2.9 increases the net charge
      of CspTm from -3.8 to +10.2, the radius of gyration of the chain is very similar
      under both conditions, indicating that protonation of acidic side chains at low
      pH results in additional hydrophobic interactions. We use a simple shared binding
      site model that describes the joint effect of urea and GdmCl, together with
      polyampholyte theory and an ion cloud model that includes the chemical free
      energy of counterion interactions and side chain protonation, to quantify this
      effect. 

PMID- 24089741
TI  - A computational kinetic model of diffusion for molecular systems.
AB  - Regulation of biomolecular transport in cells involves intra-protein steps like
      gating and passage through channels, but these steps are preceded by extra
      protein steps, namely, diffusive approach and admittance of solutes. The extra
      protein steps develop over a 10-100 nm length scale typically in a highly
      particular environment, characterized through the protein's geometry, surrounding
      electrostatic field, and location. In order to account for solute energetics and
      mobility of solutes in this environment at a relevant resolution, we propose a
      particle-based kinetic model of diffusion based on a Markov State Model
      framework. Prerequisite input data consist of diffusion coefficient and potential
      of mean force maps generated from extensive molecular dynamics simulations of
      proteins and their environment that sample multi-nanosecond durations. The
      suggested diffusion model can describe transport processes beyond microsecond
      duration, relevant for biological function and beyond the realm of molecular
      dynamics simulation. For this purpose the systems are represented by a discrete
      set of states specified by the positions, volumes, and surface elements of
      Voronoi grid cells distributed according to a density function resolving the
      often intricate relevant diffusion space. Validation tests carried out for
      generic diffusion spaces show that the model and the associated Brownian motion
      algorithm are viable over a large range of parameter values such as time step,
      diffusion coefficient, and grid density. A concrete application of the method is
      demonstrated for ion diffusion around and through the Eschericia coli
      mechanosensitive channel of small conductance ecMscS. 

PMID- 24089743
TI  - Fisher information metric for the Langevin equation and least informative models
      of continuous stochastic dynamics.
AB  - The evaluation of the Fisher information matrix for the probability density of
      trajectories generated by the over-damped Langevin dynamics at equilibrium is
      presented. The framework we developed is general and applicable to any arbitrary
      potential of mean force where the parameter set is now the full space dependent
      function. Leveraging an innovative Hermitian form of the corresponding Fokker
      Planck equation allows for an eigenbasis decomposition of the time propagation
      probability density. This formulation motivates the use of the square root of the
      equilibrium probability density as the basis for evaluating the Fisher
      information of trajectories with the essential advantage that the Fisher
      information matrix in the specified parameter space is constant. This outcome
      greatly eases the calculation of information content in the parameter space via a
      line integral. In the continuum limit, a simple analytical form can be derived to
      explicitly reveal the physical origin of the information content in equilibrium
      trajectories. This methodology also allows deduction of least informative
      dynamics models from known or available observables that are either dynamical or
      static in nature. The minimum information optimization of dynamics is performed
      for a set of different constraints to illustrate the generality of the proposed
      methodology. 

PMID- 24089744
TI  - One-dimensional embedded cluster approach to modeling CdS nanowires.
AB  - We present an embedded cluster model to treat one-dimensional nanostructures,
      using a hybrid quantum mechanical/molecular mechanical (QM/MM) approach. A
      segment of the nanowire (circa 50 atoms) is treated at a QM level of theory,
      using density functional theory (DFT) with a hybrid exchange-correlation
      functional. This segment is then embedded in a further length of wire, treated at
      an MM level of theory. The interaction between the QM and MM regions is provided
      by an embedding potential located at the interface. Point charges are placed
      beyond the ends of the wire segment in order to reproduce the Madelung potential
      of the infinite system. We test our model on the ideal system of a CdS linear
      chain, benchmarking our results against calculations performed on a periodic
      system using a plane-wave DFT approach, with electron exchange and correlation
      treated at the same level of approximation in both methods. We perform our tests
      on pure CdS and, importantly, the system containing a single In or Cu impurity.
      We find excellent agreement in the determined electronic structure using the two
      approaches, validating our embedded cluster model. As the hybrid QM/MM model
      avoids spurious interactions between charged defects, it will be of benefit to
      the analysis of the role of defects in nanowire materials, which is currently a
      major challenge using a plane-wave DFT approach. Other advantages of the hybrid
      QM/MM approach over plane-wave DFT include the ability to calculate ionization
      energies with an absolute reference and access to high levels of theory for the
      QM region which are not incorporated in most plane-wave codes. Our results concur
      with available experimental data. 

PMID- 24089745
TI  - Mapping variable ring polymer molecular dynamics: a path-integral based method
      for nonadiabatic processes.
AB  - We introduce mapping-variable ring polymer molecular dynamics (MV-RPMD), a model
      dynamics for the direct simulation of multi-electron processes. An extension of
      the RPMD idea, this method is based on an exact, imaginary time path-integral
      representation of the quantum Boltzmann operator using continuous Cartesian
      variables for both electronic states and nuclear degrees of freedom. We
      demonstrate the accuracy of the MV-RPMD approach in calculations of real-time,
      thermal correlation functions for a range of two-state single-mode model systems
      with different coupling strengths and asymmetries. Further, we show that the
      ensemble of classical trajectories employed in these simulations preserves the
      Boltzmann distribution and provides a direct probe into real-time coupling
      between electronic state transitions and nuclear dynamics. 

PMID- 24089746
TI  - Improved renormalization group theory for critical asymmetry of fluids.
AB  - We develop an improved renormalization group (RG) approach incorporating the
      critical vapor-liquid equilibrium asymmetry. In order to treat the critical
      asymmetry of vapor-liquid equilibrium, the integral measure is introduced in the
      Landau-Ginzbug partition function to achieve a crossover between the local order
      parameter in Ising model and the density of fluid systems. In the implementation
      of the improved RG approach, we relate the integral measure with the
      inhomogeneous density distribution of a fluid system and combine the developed
      method with SAFT-VR (statistical associating fluid theory of variable range)
      equation of state. The method is applied to various fluid systems including
      square-well fluid, square-well dimer fluid and real fluids such as methane (CH4),
      ethane (C2H6), trifluorotrichloroethane (C2F3Cl3), and sulfur hexafluoride (SF6).
      The descriptions of vapor-liquid equilibria provided by the developed method are
      in excellent agreement with simulation and experimental data. Furthermore, the
      improved method predicts accurate and qualitatively correct behavior of
      coexistence diameter near the critical point and produces the non-classical 3D
      Ising criticality. 

PMID- 24089747
TI  - Nested sampling in the canonical ensemble: direct calculation of the partition
      function from NVT trajectories.
AB  - Nested sampling has emerged as a powerful sampling technique to directly compute
      the partition function of a realistic molecular system. However, it does so with
      a non-standard sampling of phase space, which excludes the use of molecular
      dynamics simulations. Here we show how to use the standard canonical (NVT)
      sampling of phase space to directly compute the partition function. There are two
      components to the nested NVT sampling procedure. First, the temperatures at which
      the simulations should be run are chosen sequentially, from high to low, based on
      a histogram reweighting strategy. Second, a harmonic umbrella biasing potential
      is added, where necessary, to enhance the sampling. We also show how to evaluate
      the expectation value of an observable and compute the free energy as a function
      of an order parameter. NVT sampling procedures are common and readily available
      in conventional Monte Carlo and molecular dynamics codes. The proposed algorithm
      is easy to integrate into existing codes, which opens up the nested sampling
      technique to a wide audience. 

PMID- 24089748
TI  - Multiple Bennett acceptance ratio made easy for replica exchange simulations.
AB  - In this paper, we illustrate a practical technique to improve the efficiency of
      the so-called multiple Bennett acceptance ratio (MBAR) estimator [Shirts and
      Chodera, J. Chem. Phys. 129, 124105 (2008)] for computing thermodynamic
      expectations of physical quantities, from samples drawn from Hamiltonian or
      temperature replica exchange simulations. The methods exploit the Crooks
      fluctuation theorem [Crooks, J. Stat. Phys. 90, 1481 (1998)] for accurately
      evaluating the partition functions ratios of neighboring replicas, thus providing
      an excellent initial guess for the MBAR iterative procedure. 

PMID- 24089749
TI  - An improved semiclassical theory of radical pair recombination reactions.
AB  - We present a practical semiclassical method for computing the electron spin
      dynamics of a radical in which the electron spin is hyperfine coupled to a large
      number of nuclear spins. This can be used to calculate the singlet and triplet
      survival probabilities and quantum yields of radical recombination reactions in
      the presence of magnetic fields. Our method differs from the early semiclassical
      theory of Schulten and Wolynes [J. Chem. Phys. 68, 3292 (1978)] in allowing each
      individual nuclear spin to precess around the electron spin, rather than assuming
      that the hyperfine coupling-weighted sum of nuclear spin vectors is fixed in
      space. The downside of removing this assumption is that one can no longer obtain
      a simple closed-form expression for the electron spin correlation tensor: our
      method requires a numerical calculation. However, the computational effort
      increases only linearly with the number of nuclear spins, rather than
      exponentially as in an exact quantum mechanical calculation. The method is
      therefore applicable to arbitrarily large radicals. Moreover, it approaches
      quantitative agreement with quantum mechanics as the number of nuclear spins
      increases and the environment of the electron spin becomes more complex, owing to
      the rapid quantum decoherence in complex systems. Unlike the Schulten-Wolynes
      theory, the present semiclassical theory predicts the correct long-time behaviour
      of the electron spin correlation tensor, and it therefore correctly captures the
      low magnetic field effect in the singlet yield of a radical recombination
      reaction with a slow recombination rate. 

PMID- 24089750
TI  - Theory of vibrational equilibria and pooling at solid-diatom interfaces.
AB  - In the present paper we provide a statistical theory for the vibrational pooling
      and fluorescence time dependence observed in infrared laser excitation of CO on
      an NaCl surface. The pooling is seen in experiment and in computer simulations.
      In the theory, we assume a rapid equilibration of the quanta in the substrate and
      minimize the free energy subject to the constraint at any time t of a fixed
      number of vibrational quanta N(t). At low incident intensity, the distribution is
      limited to one-quantum exchanges with the solid and the Debye frequency of the
      solid plays a key role in limiting the range of this one-quantum domain. The
      resulting inverted vibrational equilibrium population depends only on fundamental
      parameters of the oscillator (omegae and omegaechie) and the surface (omegaD and
      T). The relation to the Treanor gas phase treatment is discussed. Unlike the
      solid phase system, the gas phase system has no Debye-constraining maximum. 

PMID- 24089751
TI  - Applying electric field to charged and polar particles between metallic plates:
      extension of the Ewald method.
AB  - We develop an efficient Ewald method of molecular dynamics simulation for
      calculating the electrostatic interactions among charged and polar particles
      between parallel metallic plates, where we may apply an electric field with an
      arbitrary size. We use the fact that the potential from the surface charges is
      equivalent to the sum of those from image charges and dipoles located outside the
      cell. We present simulation results on boundary effects of charged and polar
      fluids, formation of ionic crystals, and formation of dipole chains, where the
      applied field and the image interaction are crucial. For polar fluids, we find a
      large deviation of the classical Lorentz-field relation between the local field
      and the applied field due to pair correlations along the applied field. As
      general aspects, we clarify the difference between the potential-fixed and the
      charge-fixed boundary conditions and examine the relationship between the
      discrete particle description and the continuum electrostatics. 

PMID- 24089753
TI  - Generalized dephasing relation for fidelity and application as an efficient
      propagator.
AB  - The dephasing relation (DR), a linearization of semiclassical fidelity, is
      generalized to include the overlap of "off-diagonal" elements. The accuracy of
      the formulation is tested in integrable and chaotic systems and its scaling with
      dimensionality is studied in a Caldeira-Leggett model with many degrees of
      freedom. It is shown that the DR is often in very good agreement with numerically
      analytic quantum results and frequently outperforms an alternative semiclassical
      treatment. Most importantly, since there is no computationally expensive
      prefactor, and Monte Carlo Metropolis sampling is used to facilitate the
      calculation, the DR is found to scale remarkably well with increasing dimension.
      We further demonstrate that a propagator based on the DR can include more quantum
      coherence and outperform other popular linearized semiclassical methods, such as
      forward-backward semiclassical dynamics (FBSD) and the linearized semiclassical
      initial value representation (LSC-IVR). 

PMID- 24089752
TI  - Non-invasive estimation of dissipation from non-equilibrium fluctuations in
      chemical reactions.
AB  - We show how to extract an estimate of the entropy production from a sufficiently
      long time series of stationary fluctuations of chemical reactions. This method,
      which is based on recent work on fluctuation theorems, is direct, non-invasive,
      does not require any knowledge about the underlying dynamics and is applicable
      even when only partial information is available. We apply it to simple stochastic
      models of chemical reactions involving a finite number of states, and for this
      case, we study how the estimate of dissipation is affected by the degree of
      coarse-graining present in the input data. 

PMID- 24089754
TI  - Convergence and low temperature adaptability analysis of the high temperature
      series expansion of the free energy.
AB  - By appealing to the coupling parameter series expansion to calculate the first
      seven perturbation coefficients of the high temperature series expansion (HTSE)
      of the free energy, analysis of convergence and low temperature adaptability of
      the HTSE in calculating fluid thermodynamic properties is performed for the first
      time; the fluid thermodynamic properties considered include critical parameters,
      vapor-liquid coexistence curve, thermodynamic characteristic functions, chemical
      potential, pressure, and constant volume excess heat capacity. To proceed with
      the analysis, a well known square well model is used as sample; the well widths
      considered range over a wide interval, and the relevant temperatures amenable to
      simulation calculations (used as "exact" results to analyze the HTSE) can be both
      very high and very low. The main discoveries reached are summarized as follows:
      (1) The HTSE usually converges at the 4th-order truncation, but with decrease of
      the temperature considered, the lowest truncation order, which makes the HTSE to
      converge, tends to rise. As a conservative estimate, it is considered that the
      HTSE always converges for reduced temperature T* higher than 0.25, whereas for T*
      < 0.25 there appear signs indicating that the HTSE may diverge from the 7th-order
      truncation. (2) Within the temperature interval with T* >= 0.5, the HTSE
      converges approximately to the correct solution, and the HTSE can be reliably
      used to calculate the fluid thermodynamic properties, and within this temperature
      interval, the 4th-order truncation is enough; whereas for T* < 0.5, such as
      within the temperature interval with 0.275 <= T* <= 0.355, although the HTSE does
      converge, it does not converge to the correct solution, and the deviations
      between the HTSE calculations and MC simulations become an ever-prominent issue
      with the rising of the density, and the slopes of the thermodynamic properties
      over density are not satisfactorily represented. As a result, the HTSE is not
      suited for calculations for temperature interval T* < 0.5.

PMID- 24089755
TI  - Derivative couplings and analytic gradients for diabatic states, with an
      implementation for Boys-localized configuration-interaction singles.
AB  - We demonstrate that Boys-localized diabatic states do indeed exhibit small
      derivative couplings, as is required of quasidiabatic states. In doing so, we
      present a general formalism for calculating derivative couplings and analytic
      gradients for diabatic states. We then develop additional equations specific to
      the case of Boys-localized configuration-interaction singles (CIS)--in
      particular, the analytic gradient of the CIS dipole matrix--and we validate our
      implementation against finite-difference results. In a forthcoming paper, we will
      publish additional algorithmic and computational details and apply our method to
      the Closs energy-transfer systems as a further test of the validity of Boys
      localized diabatic states.

PMID- 24089756
TI  - Time-resolved broadband Raman spectroscopies: a unified six-wave-mixing
      representation.
AB  - Excited-state vibrational dynamics in molecules can be studied by an
      electronically off-resonant Raman process induced by a probe pulse with variable
      delay with respect to an actinic pulse. We establish the connection between
      several variants of the technique that involve either spontaneous or stimulated
      Raman detection and different pulse configurations. By using loop diagrams in the
      frequency domain, we show that all signals can be described as six wave mixing
      which depend on the same four point molecular correlation functions involving two
      transition dipoles and two polarizabilities and accompanied by a different
      gating. Simulations for the stochastic two-state-jump model illustrate the origin
      of the absorptive and dispersive features observed experimentally. 

PMID- 24089757
TI  - Mathematical methods for restricted domain ternary liquid mixture free energy
      determination using light scattering.
AB  - We extend methods of solution of a light scattering partial differential equation
      for the free energy of mixing to apply to connected, isotropic ternary liquid
      composition domains that do not touch all three binary axes. To do so we
      mathematically analyze the problem of inferring needed Dirichlet boundary data,
      and solving for the free energy, with use of hypothetical static light scattering
      measurements that correspond to dielectric composition gradient vectors that have
      distinct directions. The physical idea behind the technique is that contrasting
      absorption properties of mixture components can result in such distinctly
      directed dielectric composition gradient vectors, due to their differing
      wavelength dependences of dielectric response. At suitably chosen wavelengths,
      contrasting light scattering efficiency patterns in the ternary composition
      triangle can then correspond to the same underlying free energy, and enlarge the
      scope of available information about the free energy, as shown here. We show how
      to use distinctly directed dielectric gradients to measure the free energy on
      both straight lines and curves within the ternary composition triangle, so as to
      provide needed Dirichlet conditions for light scattering partial differential
      equation solution. With use of Monte Carlo simulations of noisy light scattering
      data, we provide estimates of the overall system measurement time and sample
      spacing needed to determine the free energy to a desired degree of accuracy, for
      various angles between the assumed dielectric gradient vectors, and indicate how
      the measurement time depends on instrumental throughput parameters. The present
      analysis methods provide a way to use static light scattering to measure,
      directly, mixing free energies of many systems that contain such restricted
      liquid domains, including aqueous solutions of biological macromolecules,
      micellar mixtures and microemulsions, and many small molecule systems that are
      important in separation technology. 

PMID- 24089758
TI  - A comparison of reduced coordinate sets for describing protein structure.
AB  - In all-atom molecular simulation studies of proteins, each atom in the protein is
      represented by a point mass and interactions are defined in terms of the atomic
      positions. In recent years, various simplified approaches have been proposed.
      These approaches aim to improve computational efficiency and to provide a better
      physical insight. The simplified models can differ widely in their description of
      the geometry and the interactions inside the protein. This study explores the
      most fundamental choice in the simplified protein models: the choice of a
      coordinate set defining the protein structure. A simplified model can use fewer
      point masses than the all-atom model and/or eliminate some of the internal
      coordinates of the molecule by setting them to an average or ideal value. We look
      at the implications of such choices for the overall protein structure. We find
      that care must be taken for angular coordinates, where even very small variations
      can lead to significant changes in the positions of far away atoms. In
      particular, we show that the phi/psi torsion angles are not a sufficient
      coordinate set, whereas another coordinate set with two degrees of freedom per
      residue, virtual Calpha backbone bond, and torsion angles performs
      satisfactorily. 

PMID- 24089759
TI  - Perturbative approximations to single and double spin flip equation of motion
      coupled cluster singles doubles methods.
AB  - Spin flip equation of motion coupled cluster (EOM-SF-CC) can correctly treat
      situations involving electronic degeneracies or near degeneracies, e.g., bond
      breaking, di- and tri-radicals, etc. However, for large systems EOM-SF-CC (even
      in single and double excitations) is computationally prohibitively expensive.
      Therefore, earlier approximations to EOM-SF-CC methods such as spin flip
      configuration interaction singles with perturbative doubles (SF-CIS(D)) have been
      proposed. In this work, we present a new perturbative approximation to EOM-SF-CC,
      which has been found to be more accurate than SF-CIS(D). The capabilities,
      advantages, and timings of the new approach have been demonstrated considering
      the singlet-triplet gaps in di- and triradicals as well as bond breaking
      examples. The method is extended to double spin flip EOM-CC and its capabilities
      have been tested. 

PMID- 24089760
TI  - Solving the Schrodinger eigenvalue problem by the imaginary time propagation
      technique using splitting methods with complex coefficients.
AB  - The Schrodinger eigenvalue problem is solved with the imaginary time propagation
      technique. The separability of the Hamiltonian makes the problem suitable for the
      application of splitting methods. High order fractional time steps of order
      greater than two necessarily have negative steps and cannot be used for this
      class of diffusive problems. However, there exist methods which use fractional
      complex time steps with positive real parts which can be used with only a
      moderate increase in the computational cost. We analyze the performance of this
      class of schemes and propose new methods which outperform the existing ones in
      most cases. On the other hand, if the gradient of the potential is available,
      methods up to fourth order with real and positive coefficients exist. We also
      explore this case and propose new methods as well as sixth-order methods with
      complex coefficients. In particular, highly optimized sixth-order schemes for
      near integrable systems using positive real part complex coefficients with and
      without modified potentials are presented. A time-stepping variable order
      algorithm is proposed and numerical results show the enhanced efficiency of the
      new methods.

PMID- 24089761
TI  - Frozen rotor approximation in the mixed quantum/classical theory for collisional
      energy transfer: application to ozone stabilization.
AB  - A frozen-rotor approximation is formulated for the mixed quantum/classical theory
      of collisional energy transfer and ro-vibrational energy flow [M. Ivanov and D.
      Babikov, J. Chem. Phys. 134, 144107 (2011)]. Numerical tests are conducted to
      assess its efficiency and accuracy, compared to the original version of the
      method, where rotation of the molecule in space is treated explicitly and
      adiabatically. New approach is considerably faster and helps blocking the
      artificial ro-vibrational transitions at the pre- and post-collisional stages of
      the process. Although molecular orientation in space is fixed, the energy
      exchange between rotational, vibrational, and translational digresses of freedom
      still occurs, allowing to compute ro-vibrational excitation and quenching.
      Behavior of the energy transfer function through eight orders of magnitude range
      of values and in a broad range of DeltaE is reproduced well. In the range of
      moderate -500 <= DeltaE <= +500 cm(-1) the approximate method is rather accurate.
      The absolute values of stabilization cross sections for scattering resonances
      trapped behind the centrifugal threshold are a factor 2-to-3 smaller (compared to
      the explicit-rotation approach). This performance is acceptable and similar to
      the well-known sudden-rotation approximation in the time-independent inelastic
      scattering methods.

PMID- 24089762
TI  - Spectroscopic evidence of the presence of an activation barrier in the otherwise
      barrierless excited state potential energy surface of auramine-O: a femtosecond
      fluorescence up-conversion study.
AB  - A widely acclaimed model for the excited state relaxation dynamics of auramine-O
      involves orientational relaxation of dimethylanilino moieties along the
      barrierless excited state potential energy surface (PES). Such a model would
      necessitate similar excited state dynamics in media offering similar viscous
      drag. However, we have noticed an interesting experimental observation showing
      auramine-O to have ~8 times larger fluorescence quantum yield in chloroform than
      in methanol, though both the solvents have the same viscosity. The femtosecond
      fluorescence transients of auramine-O in chloroform surprisingly depict a rise in
      fluorescence transients, which has not been observed before. This, along with the
      simultaneous observation of unexpectedly large fluorescence lifetime and multi
      exponential transients (in chloroform) questions the thoroughly accepted
      barrierless model of auramine-O relaxation dynamics, as the barrierless model
      would demand a short lifetime and single-exponential decay. Temperature dependent
      quantum yield measurements along with solvent dependent excited state multi
      coordinate time-dependent density functional theory calculations further unveil
      the exact nature of PES. All these results concomitantly conclude that, at-least
      in chloroform, upon photo-excitation auramine-O must pass over an activation
      barrier before damping the excited state population into ground state via a sink
      function through adiabatic coupling of the electronic states.

PMID- 24089763
TI  - Atomistic simulations of methane interactions with an atmospheric moisture.
AB  - Methane is an extremely effective absorber of radiation, i.e., it is a relatively
      potent greenhouse gas, and the increased concentration of methane in the
      atmosphere must influence earth's radiation balance. The adsorption of one to six
      methane molecules by water clusters is studied by the method of molecular
      dynamics under near-atmospheric conditions. The capture of methane molecules by
      water clusters produces an increase in the integrated intensity of IR absorbance
      and the reflection coefficient. The Raman spectrum of the system is considerably
      depleted due to the addition of methane molecules to the disperse water system.
      The observed emission power of a dispersed aqueous system with adsorbed methane
      molecules has appreciably increased relative to the analogous characteristics of
      the pure water cluster system. The Voronoi polyhedra and simplified ones
      constructed within the framework of molecular-dynamic model of clusters are used
      for the analysis of the structure changes occurring with increasing the number of
      adsorbed CH4 molecules. 

PMID- 24089764
TI  - Parity-dependent oscillations in collisional polarization transfer: CN(A2Pi, v =
      4) + Ar.
AB  - We report the first systematic experimental and theoretical study of the state-to
      state transfer of rotational angular momentum orientation in a (2)Pi-rare gas
      system. CN(X(2)Sigma(+)) was produced by pulsed 266 nm photolysis of ICN in a
      thermal bath (296 K) of Ar collider gas. A pulsed circularly polarized tunable
      dye laser prepared CN(A(2)Pi, v = 4) in two fully state-selected initial levels,
      j = 6.5 F1e and j = 10.5 F2f, with a known laboratory-frame orientation. Both the
      prepared levels and a range of product levels, j' F1e and j' F2f, were monitored
      using the circular polarized output of a tunable diode laser via cw frequency
      modulated (FM) spectroscopy in stimulated emission on the CN(A-X) (4,2) band. The
      FM Doppler lineshapes for co-rotating and counter-rotating pump-and-probe
      geometries reveal the time-dependence of the populations and orientations.
      Kinetic fitting was used to extract the state-to-state population transfer rate
      constants and orientation multipole transfer efficiencies (MTEs), which quantify
      the degree of conservation of initially prepared orientation in the product
      level. Complementary full quantum scattering (QS) calculations were carried out
      on recently computed ab initio potential energy surfaces. Collision-energy
      dependent tensor cross sections for ranks K = 0 and 1 were computed for
      transitions from both initial levels to all final levels. These quantities were
      integrated over the thermal collision energy distribution to yield predictions of
      the experimentally observed state-to-state population transfer rate constants and
      MTEs. Excellent agreement between experiment and theory is observed for both
      measured quantities. Dramatic oscillations in the MTEs are observed, up to and
      including changes in the sign of the orientation, as a function of even/odd
      Deltaj within a particular spin-orbit and e/f manifold. These oscillations, along
      with those also observed in the state-to-state rate constants, reflect the
      rotational parity of the final level. In general, parity-conserving collisions
      conserve rotational orientation, while parity-changing collisions result in large
      changes in the orientation. The QS calculations show that the dynamics of the
      collisions leading to these different outcomes are fundamentally different. We
      propose that the origin of this behavior lies in interferences between collisions
      that sample the even and odd-lambda terms in the angular expansions of the PESs.

PMID- 24089765
TI  - Pyrolysis of furan in a microreactor.
AB  - A silicon carbide microtubular reactor has been used to measure branching ratios
      in the thermal decomposition of furan, C4H4O. The pyrolysis experiments are
      carried out by passing a dilute mixture of furan (approximately 0.01%) entrained
      in a stream of helium through the heated reactor. The SiC reactor (0.66 mm i.d.,
      2 mm o.d., 2.5 cm long) operates with continuous flow. Experiments were performed
      with a reactor inlet pressure of 100-300 Torr and a wall temperature between 1200
      and 1600 K; characteristic residence times in the reactor are 60-150 MUs. The
      unimolecular decomposition pathway of furan is confirmed to be: furan (+ M) ?
      alpha-carbene or beta-carbene. The alpha-carbene fragments to CH2=C=O + HC=CH
      while the beta-carbene isomerizes to CH2=C=CHCHO. The formyl allene can isomerize
      to CO + CH3C=CH or it can fragment to H + CO + HCCCH2. Tunable synchrotron
      radiation photoionization mass spectrometry is used to monitor the products and
      to measure the branching ratio of the two carbenes as well as the ratio of
      [HCCCH2]/[CH3C=CH]. The results of these pyrolysis experiments demonstrate a
      preference for 80%-90% of furan decomposition to occur via the beta-carbene. For
      reactor temperatures of 1200-1400 K, no propargyl radicals are formed. As the
      temperature rises to 1500-1600 K, at most 10% of the decomposition of CH2=C=CHCHO
      produces H + CO + HCCCH2 radicals. Thermodynamic conditions in the reactor have
      been modeled by computational fluid dynamics and the experimental results are
      compared to the predictions of three furan pyrolysis mechanisms. Uncertainty in
      the pressure-dependency of the initiation reaction rates is a possible a source
      of discrepancy between experimental results and theoretical predictions.

PMID- 24089766
TI  - Intramolecular photoelectron diffraction in the gas phase.
AB  - We report unambiguous experimental and theoretical evidence of intramolecular
      photoelectron diffraction in the collective vibrational excitation that
      accompanies high-energy photoionization of gas-phase CF4, BF3, and CH4 from the
      1s orbital of the central atom. We show that the ratios between vibrationally
      resolved photoionization cross sections (v-ratios) exhibit pronounced
      oscillations as a function of photon energy, which is the fingerprint of electron
      diffraction by the surrounding atomic centers. This interpretation is supported
      by the excellent agreement between first-principles static-exchange and time
      dependent density functional theory calculations and high resolution
      measurements, as well as by qualitative agreement at high energies with a model
      in which atomic displacements are treated to first order of perturbation theory.
      The latter model allows us to rationalize the results for all the v-ratios in
      terms of a generalized v-ratio, which contains information on the structure of
      the above three molecules and the corresponding molecular cations. A fit of the
      measured v-ratios to a simple formula based on this model suggests that the
      method could be used to obtain structural information of both neutral and ionic
      molecular species. 

PMID- 24089767
TI  - Photodissociation dynamics of C4H2 at 164.41 nm: competitive dissociation
      pathways.
AB  - Photodissociation dynamics of C4H2 at 164.41 nm through the Rydberg state
      R((1)Sigmau) have been studied using the high-resolution H atom Rydberg tagging
      technique. Experimental evidences show that two different predissociation
      pathways exist to form the ground C4H (X(2)Sigma(+)) and electronically excited
      C4H (A(2)Pi) products: the former has statistical and isotropic translational
      energy distribution through internal conversion (IC) to the ground state, while
      the latter has non-statistical and anisotropic translational energy distribution
      through IC to the excited repulsive state. The vibrational progressions of C4H
      (A(2)Pi) products have also been observed and assigned. 

PMID- 24089768
TI  - Tuning of character of the N-O bond in HONO from covalent to protocovalent by
      different types of intramolecular interactions.
AB  - Quantum-chemical calculations of the H-O-N=O molecule in the equilibrium and
      transition states and the complexes of the HONO with BH3, study of the
      intramolecular interactions using NBO theory, and investigation of the electron
      distribution on the basis of topological analysis of the ELF function clearly
      indicate the influence of the n-pi* conjugation and n-sigma* hyperconjugation
      interactions on a par with exchange repulsion of lone pairs the character of the
      N-O bond. It is shown that repulsion between lone pairs of oxygen and nitrogen
      atoms causes the elongation of the N-O bond only but character of this bond
      remains covalent. The interaction between lone pair of the terminal oxygen atom
      and antibonding orbital of the N-O bond (n-sigma* hyperconjugation) coincides
      with influence of repulsion and reinforces it changing the character of the N-O
      bond from covalent to protocovalent. In contrary, the n-pi* conjugation
      interaction between lone pairs of the bridged oxygen atom and pi-orbital of the
      N=O double bond leads to the strengthening of the N-O bond making it more
      covalent.

PMID- 24089769
TI  - Photoelectron imaging of XUV photoionization of CO2 by 13-40 eV synchrotron
      radiation.
AB  - Valence band photoionization of CO2 has been studied by photoelectron
      spectroscopy using a velocity map imaging spectrometer and synchrotron radiation.
      The measured data allow retrieving electronic and vibrational branching ratios,
      vibrationally resolved asymmetry parameters, and the total electron yield which
      includes multiple strong resonances. Additionally, the spectrum of low kinetic
      energy electrons has been studied in the resonant region, and the evolution with
      photon energy of one of the forbidden transitions present in the slow
      photoelectrons spectrum has been carefully analyzed, indicating that in the
      presence of auto-ionizing resonances the vibrational populations of the ion are
      significantly redistributed. 

PMID- 24089770
TI  - Enhancement of lanthanide evaporation by complexation: dysprosium tri-iodide
      mixed with indium iodide and thulium tri-iodide mixed with thallium iodide.
AB  - The vapors in equilibrium with condensates of DyI3, DyI3/InI, TmI3, and TmI3/TlI
      were observed over the temperature range from 900 K to 1400 K using x-ray induced
      fluorescence. The total densities of each element (Dy, Tm, In, Tl, and I) in the
      vapor, summed over all atomic and molecular species, were determined. Dramatic
      enhancements in the total vapor densities of Dy and Tm were observed in the
      vapors over DyI3/InI and TmI3/TlI as compared to the vapors over pure DyI3 and
      pure TmI3, respectively. An enhancement factor exceeding 10 was observed for Dy
      at T ~ 1020 K, decreasing to 0 at T ~ 1250 K. An enhancement factor exceeding 20
      was observed for Tm at T ~ 1040 K, decreasing to 0 at T ~ 1300 K. Such
      enhancements are expected from the formation of the vapor-phase hetero-complexes
      DyInI4 and TmTlI4. Numerical simulations of the thermo-chemical equilibrium
      suggest the importance of additional complexes in liquid phases. A description of
      the measurement technique is given. Improvements in the absolute calibration lead
      to an approximately 40% correction to previously reported preliminary results [J.
      J. Curry et al., Chem. Phys. Lett. 507, 52 (2011); Appl. Phys. Lett. 100, 083505
      (2012)]. 

PMID- 24089771
TI  - MODE-specific deactivation of adenine at the singlet excited states.
AB  - The deactivation process of adenine excited near the band origin of the lowest
      pipi* state ((1)L(b)) is investigated using picosecond (ps) time-resolved
      photoionization spectroscopy. The transients obtained with a ps pump pulse at the
      sharp vibronic bands, 36,105 cm(-1) (D) and 36,248 cm(-1) (E), in the resonant
      two-photon ionization spectrum exhibit a bi-exponential decay with two distinct
      time constants of tau1 ~ 2 ps and tau2 > 100 ps, whereas the transients with the
      pump at other wavenumbers in this energy region show a single exponential decay
      with tau = 1-2 ps. We suggest that the tau1 represents the lifetimes of the
      (1)npi* energy levels near the D and E peaks, which are excited together by the
      ps pump pulse having a broad spectral bandwidth, and the tau2 shows the lifetimes
      of D and E peaks. The long lifetime of D level is attributed to a small barrier
      for internal conversion from the minimum of the (1)L(b) state to the (1)npi*
      state. On the other hand, the long lifetime of E level is ascribed to the nuclear
      configuration of adenine at this level, which is unfavorable to reach the seam of
      the conical intersection leading to nearly barrierless deactivation to the
      electronic ground state. This study shows that the ps time-resolved spectroscopy
      provides a powerful tool to study mode- and energy-specific deactivation
      processes occurring in a multi-dimensional potential energy surface.

PMID- 24089772
TI  - A DFT based equilibrium study on the hydrolysis and the dehydration reactions of
      MgCl2 hydrates.
AB  - Magnesium chloride hydrates are characterized as promising energy storage
      materials in the built-environment. During the dehydration of these materials,
      there are chances for the release of harmful HCl gas, which can potentially
      damage the material as well as the equipment. Hydrolysis reactions in magnesium
      chloride hydrates are subject of study for industrial applications. However, the
      information about the possibility of hydrolysis reaction, and its preference over
      dehydration in energy storage systems is still ambiguous at the operating
      conditions in a seasonal heat storage system. A density functional theory level
      study is performed to determine molecular structures, charges, and harmonic
      frequencies in order to identify the formation of HCl at the operating
      temperatures in an energy storage system. The preference of hydrolysis over
      dehydration is quantified by applying thermodynamic equilibrium principles by
      calculating Gibbs free energies of the hydrated magnesium chloride molecules. The
      molecular structures of the hydrates (n = 0, 1, 2, 4, and 6) of MgCl2 are
      investigated to understand the stability and symmetry of these molecules. The
      structures are found to be noncomplex with almost no meta-stable isomers, which
      may be related to the faster kinetics observed in the hydration of chlorides
      compared to sulfates. Also, the frequency spectra of these molecules are
      calculated, which in turn are used to calculate the changes in Gibbs free energy
      of dehydration and hydrolysis reactions. From these calculations, it is found
      that the probability for hydrolysis to occur is larger for lower hydrates.
      Hydrolysis occurring from the hexa-, tetra-, and di-hydrate is only possible when
      the temperature is increased too fast to a very high value. In the case of the
      mono-hydrate, hydrolysis may become favorable at high water vapor pressure and at
      low HCl pressure. 

PMID- 24089773
TI  - State-to-state quantum dynamics of the N(4S) + CH(X2Pi) -> CN(X2Sigma+,A2Pi) +
      H(2S) reactions.
AB  - The reactions between N((4)S) and CH(X(2)Pi) lead to H((2)S) plus CN in its two
      lowest electronic states (X(2)Sigma(+) and A(2)Pi), which are responsible for the
      interstellar CN formation. Accurate quantum dynamics of these reactions are
      investigated on new global potential energy surfaces of the two lowest-lying
      triplet states of HCN (1(3)A' and 1(3)A") fitted to more than 37,000 points at
      the internally contracted multi-reference configuration interaction level with
      the Davidson correction. The pathways for these highly exothermic and barrierless
      reactions feature both the HCN and HNC wells. Long-lived resonances supported by
      these wells manifest in reaction probabilities as numerous oscillations,
      particularly for low J partial waves. The 1(3)A" state is found to be more
      reactive than the 1(3)A' state, due apparently to its more attractive nature in
      the entrance channel. The CN products in both electronic states are highly
      excited in both vibrational and rotational degrees of freedom. The near forward
      backward symmetric differential cross sections are consistent with a complex
      forming mechanism.

PMID- 24089774
TI  - Theoretical investigation on the 2e/12c bond and second hyperpolarizability of
      azaphenalenyl radical dimers: strength and effect of dimerization.
AB  - An increasing number of chemists have focused on the investigations of two
      electron/multicenter bond (2e/mc) that was first introduced to describe the
      structure of radical dimers. In this work, the dimerization of two isoelectronic
      radicals, triazaphenalenyl (TAP) and hexaazaphenalenyl (HAP) has been
      investigated in theory. Results show TAP2 is a stable dimer with stronger 2e/12c
      bond and larger interaction energy, while HAP2 is a less stable dimer with larger
      diradical character. Interestingly, the ultraviolet-visible absorption spectra
      suggest that the dimerization induces a longer wavelength absorption in visible
      area, which is dependent on the strength of dimerization. Significantly, the
      amplitude of second hyperpolarizability (gamma(yyyy)) of HAP2 is 1.36 * 10(6)
      a.u. that is larger than 7.79 * 10(4) a.u. of TAP2 because of the larger
      diradical character of HAP2. Therefore, the results indicate that the strength of
      radical dimerization can be effectively detected by comparing the magnitude of
      third order non-linear optical response, which is beneficial for further
      theoretical and experimental studies on the properties of complexes formed by
      radical dimerization.

PMID- 24089775
TI  - Photolabile xenon hydrides: a case study of HXeSH and HXeH.
AB  - The photo-induced transformations of HXeSH and HXeH under the action of IR and
      visible light have been studied using FTIR spectroscopy. The xenon hydrides were
      produced by the X-ray induced decomposition of H2S and its isotopomers in a solid
      xenon matrix at 7.5 K followed by thermal annealing at the temperatures up to 45
      K. Selective IR-induced photodissociation of HXeSH at 3500-2500 cm(-1) was
      attributed to vibrational excitation of the 3nu(H-Xe) mode. The IR
      photodecomposed HXeSH molecules can be almost quantitative recovered below 22 K
      with very small effective activation energy (~20 meV) indicating local character
      of this process. Analysis of the photoactivity of xenon hydrides in the visible
      region revealed previously unknown absorptions for HXeSH (in the region of 400
      700 nm) and HXeH (above 700 nm). The decomposition of HXeH occurs due to both
      direct photolysis and reactions of "hot" H atoms produced from the
      photodissociation of HXeSH. The efficiency of thermal recovery for both xenon
      hydrides after photolysis with visible light was found to be dependent on the
      excitation wavelength, which was explained by the effect of photon energy on
      spatial distribution of the dissociation fragments.

PMID- 24089776
TI  - A multireference configuration interaction study of CuB and CuAl molecular
      constants and photoionization spectra.
AB  - Accurate potential energy curves and molecular constants for the low-lying
      electronic states of CuX(y) (X = B, Al; y = 0, +1) were investigated using the
      complete active space self-consistent field/multireference configuration
      interaction (MRCI) methodology with aug-cc-pV5Z basis set. The photoionization
      spectra of CuX were computed, showing electron detachment in the region of far
      ultraviolet. The results complement the previous theoretical characterizations
      and the few experimental studies. A comparative analysis was carried out
      concerning the different choices of reference configuration state functions in
      the MRCI calculations with and without the contribution of scalar relativistic
      effects. The results obtained with a small reference set adequately constructed
      are competitive to those using a much larger number of configuration state
      functions, and also the scalar relativistic effects improve significantly the
      molecular constants in this kind of system containing a 3d metal atom. 

PMID- 24089777
TI  - Ro-vibrational relaxation of HCN in collisions with He: rigid bender treatment of
      the bending-rotation interaction.
AB  - We present a new theoretical method to treat atom-rigid bender inelastic
      collisions at the Close Coupling (RB-CC) level in the space fixed frame. The
      coupling between rotation and bending is treated exactly within the rigid bender
      approximation and we obtain the cross section for the rotational transition
      between levels belonging to different bending levels. The results of this
      approach are compared with those obtained when using the rigid bender averaged
      approximation (RBAA) introduced in our previous work dedicated to this system. We
      discuss the validity of this approximation and of the previous studies based on
      rigid linear HCN. We find that l-type transitions cross sections have to be
      calculated at the RB-CC level for the He-HCN collision while pure rotational
      transitions cross sections may be calculated accurately at the RBAA level. 

PMID- 24089778
TI  - The vibrational dependence of dissociative recombination: cross sections for N2+.
AB  - Theoretical ab initio calculations are reported of the cross sections for
      dissociative recombination of the lowest four excited vibrational levels of N2(+)
      at electron energies from 0.001 to 1.0 eV. Rydberg vibrational levels
      contributing to the cross section structures are identified as are dissociative
      channels contributing more than 10(-16) cm(2) to the total cross sections. In
      contrast to the prior study of v = 0 (S. L. Guberman, J. Chem. Phys. 137, 074309
      (2012)), which showed 2(3)Piu to be the dominant dissociative channel, 4(3)Piu is
      dominant for v = 1. Both 2 and 4(3)Piu are major routes for dissociative
      recombination from v = 2-4. Other routes including 2(3)Sigmau(+), 3(3)Piu,
      2(1)Piu, 2(3)Pig, 2(1)Sigmag(+), 1(1)Deltag, and b('1)Sigmau(+) are significant
      in narrow energy ranges. The results show that minor dissociative routes,
      included here for N2(+), must be included in theoretical studies of other
      molecular ions (including the simplest ions H2(+) and H3(+)) if cross section
      agreement is to be found with future high resolution dissociative recombination
      experiments. The calculated predissociation lifetimes of the Rydberg resonances
      are used in a detailed comparison to two prior storage ring experiments in order
      to determine if the prior assumption of isotropic atomic angular distributions at
      "zero" electron energy is justified. The prior experimental assumption of
      comparable cross sections for v = 0-3 is shown to be the case at "zero" but not
      at nonzero electron energies. Circumstances are identified in which indirect
      recombination may be visualized as a firefly effect.

PMID- 24089779
TI  - Quantum simulations of the hydrogen molecule on ammonia clusters.
AB  - Mixed ammonia-hydrogen molecule clusters [H2-(NH3)n] have been studied with the
      aim of exploring the quantitative importance of the H2 quantum motion in defining
      their structure and energetics. Minimum energy structures have been obtained
      employing genetic algorithm-based optimization methods in conjunction with
      accurate pair potentials for NH3-NH3 and H2-NH3. These include both a full 5D
      potential and a spherically averaged reduced surface mimicking the presence of a
      para-H2. All the putative global minima for n >= 7 are characterized by H2 being
      adsorbed onto a rhomboidal ammonia tetramer motif formed by two double donor and
      two double acceptor ammonia molecules. In a few cases, the choice of specific
      rhombus seems to be directed by the vicinity of an ammonia ad-molecule. Diffusion
      Monte Carlo simulations on a subset of the species obtained highlighted important
      quantum effects in defining the H2 surface distribution, often resulting in
      populating rhomboidal sites different from the global minimum one, and showing a
      compelling correlation between local geometrical features and the relative
      stability of surface H2. Clathrate-like species have also been studied and
      suggested to be metastable over a broad range of conditions if formed. 

PMID- 24089780
TI  - The glassy and supercooled state of elemental sulfur: vibrational modes,
      structure metastability, and polymer content.
AB  - We report a detailed investigation of vibrational modes, structure, and dynamics
      of elemental sulfur in the glassy and the supercooled state, using Raman
      scattering and ab initio calculations. Polarized Raman spectra are recorded--for
      sulfur quenched from 473 K--over a broad temperature range from 93 K to 273 K
      where the supercooled liquid crystallized. The temperature induced shifts of the
      majority of the vibrational modes are determined and compared with the
      corresponding ones of crystalline sulfur. Analysis of the reduced isotropic
      spectra showed that the structure of the quenched product is composed of eight
      member rings (S8) and polymeric chains (SMU) with a relative fraction comparable
      to that of the parent liquid at 473 K. Low temperature spectra, where spectral
      line broadening due to thermal effects is limited, revealed that two different
      polymeric species are present in the glass with distinct vibrational frequencies.
      Their interpretation was assisted by ab initio calculations used to simulate the
      vibrational frequencies of polymeric chains S(8k) (k = 1, ..., 7). Theoretical
      results exhibit an increasing breathing mode frequency for sulfur chains up to k
      = 2, although it remains constant beyond the above value. The polymeric content
      is metastable; heating the glass above its glass transition temperature, T(g),
      destabilizes the chains and drives them back to the more thermodynamically stable
      rings. This bond interchange mechanism provides the structural origin of a
      secondary relaxation process in supercooled sulfur reported long ago, which has
      been also considered as a complication in the correct fragility estimation of
      this material. Finally, the Boson peak of the glass was found to exhibit strong
      temperature dependence even at temperatures below T(g).

PMID- 24089781
TI  - Glass transition temperature and topological constraints of sodium borophosphate
      glass-forming liquids.
AB  - Sodium borophosphate glasses exhibit intriguing mixed network former effect, with
      the nonlinear compositional dependence of their glass transition temperature as
      one of the most typical examples. In this paper, we establish the widely
      applicable topological constraint model of sodium borophosphate mixed network
      former glasses to explain the relationship between the internal structure and
      nonlinear changes of glass transition temperature. The application of glass
      topology network was discussed in detail in terms of the unified methodology for
      the quantitative distribution of each coordinated boron and phosphorus units and
      glass transition temperature dependence of atomic constraints. An accurate
      prediction of composition scaling of the glass transition temperature was
      obtained based on topological constraint model. 

PMID- 24089782
TI  - Computational studies of the glass-forming ability of model bulk metallic
      glasses.
AB  - Bulk metallic glasses (BMGs) are produced by rapidly thermally quenching
      supercooled liquid metal alloys below the glass transition temperature at rates
      much faster than the critical cooling rate R(c) below which crystallization
      occurs. The glass-forming ability of BMGs increases with decreasing R(c), and
      thus good glass-formers possess small values of R(c). We perform molecular
      dynamics simulations of binary Lennard-Jones (LJ) mixtures to quantify how key
      parameters, such as the stoichiometry, particle size difference, attraction
      strength, and heat of mixing, influence the glass-formability of model BMGs. For
      binary LJ mixtures, we find that the best glass-forming mixtures possess atomic
      size ratios (small to large) less than 0.92 and stoichiometries near 50:50 by
      number. In addition, weaker attractive interactions between the smaller atoms
      facilitate glass formation, whereas negative heats of mixing (in the
      experimentally relevant regime) do not change R(c) significantly. These results
      are tempered by the fact that the slowest cooling rates achieved in our
      simulations correspond to ~10(11) K/s, which is several orders of magnitude
      higher than R(c) for typical BMGs. Despite this, our studies represent a first
      step in the development of computational methods for quantitatively predicting
      glass-formability.

PMID- 24089783
TI  - Assessing the non-ideality of the CO2-CS2 system at molecular level: a Raman
      scattering study.
AB  - The dense phase of CO2-CS2 mixtures has been analysed by Raman spectroscopy as a
      function of the CO2 concentration (0.02-0.95 mole fractions) by varying the
      pressure (0.5 MPa up to 7.7 MPa) at constant temperature (313 K). The polarised
      and depolarised spectra of the induced (nu2, nu3) modes of CS2 and of the nu1
      2nu2 Fermi resonance dyad of both CO2 and CS2 have been measured. Upon dilution
      with CO2, the evolution of the spectroscopic observables of all these modes
      displays a "plateau-like" region in the CO2 mole fraction 0.3-0.7 never
      previously observed in CO2-organic liquids mixtures. The bandshape and intensity
      of the induced modes of CS2 are similar to those of pure CS2 up to equimolar
      concentration, after which variations occur. The preservation of the local
      ordering from pure CS2 to equimolar concentration together with the non-linear
      evolution of the spectroscopic observables allows inferring that two solvation
      regimes exist with a transition occurring in the plateau domain. In the first
      regime, corresponding to CS2 concentrated mixtures, the liquid phase is
      segregated with dominant CS2 clusters, whereas, in the second one, CO2 monomers
      and dimers and CO2-CS2 hetero-dimers coexist dynamically on a picosecond time
      scale. It is demonstrated that the subtle interplay between attractive and
      repulsive interactions which provides a molecular interpretation of the non
      ideality of the CO2-CS2 mixture allows rationalizing the volume expansion and the
      existence of the plateau-like region observed in the pressure-composition diagram
      previously ascribed to the proximity of an upper critical solution temperature at
      lower temperatures. 

PMID- 24089784
TI  - Molecular simulation of aqueous electrolytes: water chemical potential results
      and Gibbs-Duhem equation consistency tests.
AB  - This paper deals with molecular simulation of the chemical potentials in aqueous
      electrolyte solutions for the water solvent and its relationship to chemical
      potential simulation results for the electrolyte solute. We use the Gibbs-Duhem
      equation linking the concentration dependence of these quantities to test the
      thermodynamic consistency of separate calculations of each quantity. We consider
      aqueous NaCl solutions at ambient conditions, using the standard SPC/E force
      field for water and the Joung-Cheatham force field for the electrolyte. We
      calculate the water chemical potential using the osmotic ensemble Monte Carlo
      algorithm by varying the number of water molecules at a constant amount of
      solute. We demonstrate numerical consistency of these results in terms of the
      Gibbs-Duhem equation in conjunction with our previous calculations of the
      electrolyte chemical potential. We present the chemical potential vs molality
      curves for both solvent and solute in the form of appropriately chosen analytical
      equations fitted to the simulation data. As a byproduct, in the context of the
      force fields considered, we also obtain values for the Henry convention standard
      molar chemical potential for aqueous NaCl using molality as the concentration
      variable and for the chemical potential of pure SPC/E water. These values are in
      reasonable agreement with the experimental values. 

PMID- 24089785
TI  - Cooee bitumen: chemical aging.
AB  - We study chemical aging in "Cooee bitumen" using molecular dynamic simulations.
      This model bitumen is composed of four realistic molecule types: saturated
      hydrocarbon, resinous oil, resin, and asphaltene. The aging reaction is modelled
      by the chemical reaction: "2 resins -> 1 asphaltene." Molecular dynamic
      simulations of four bitumen compositions, obtained by a repeated application of
      the aging reaction, are performed. The stress autocorrelation function, the fluid
      structure, the rotational dynamics of the plane aromatic molecules, and the
      diffusivity of each molecule are determined for the four different compositions.
      The aging reaction causes a significant dynamics slowdown, which is correlated to
      the aggregation of asphaltene molecules in larger and dynamically slower
      nanoaggregates. Finally, a detailed description of the role of each molecule
      types in the aggregation and aging processes is given. 

PMID- 24089786
TI  - Proton transfer and the diffusion of H+ and OH- ions along water wires.
AB  - Hydrogen and hydroxide ion transport in narrow carbon nanotubes (CNTs) of
      diameter 8.1 A and lengths up to 582 A are investigated by molecular dynamics
      simulations using a dissociating water model. The diffusion coefficients of the
      free ions in an open chain are significantly larger than in periodically
      replicated wires that necessarily contain D or L end defects, and both are higher
      than they are in bulk water. The free hydroxide ion diffuses faster than the free
      hydronium ion in short CNTs, unlike diffusion in liquid water, and both
      coefficients increase and converge to nearly the same value with increasing tube
      length. The diffusion coefficients of the two ions increase further when the
      tubes are immersed in a water reservoir and they move easily out of the tube,
      suggesting an additional pathway for proton transport via OH(-) ions in
      biological channels.

PMID- 24089787
TI  - Crystallization in glassy suspensions of hard ellipsoids.
AB  - We have carried out computer simulations of overcompressed suspensions of hard
      monodisperse ellipsoids and observed their crystallization dynamics. The system
      was compressed very rapidly in order to reach the regime of slow, glass-like
      dynamics. We find that, although particle dynamics become sub-diffusive and the
      intermediate scattering function clearly develops a shoulder, crystallization
      proceeds via the usual scenario: nucleation and growth for small
      supersaturations, spinodal decomposition for large supersaturations. In
      particular, we compared the mobility of the particles in the regions where
      crystallization set in with the mobility in the rest of the system. We did not
      find any signature in the dynamics of the melt that pointed towards the imminent
      crystallization events. 

PMID- 24089788
TI  - The compressibility and surface tension product of molten salts.
AB  - Products of the isothermal compressibility, kappaT, and the surface tension,
      sigma, that have been discussed in the literature for liquids in general are
      shown for over 60 molten salts. The applications of the scaled particle theory of
      Mayer and the simplified corresponding states correlation of Harada et al. [Ind.
      Eng. Chem. Fund. 22, 116 (1983)] lead to calculated values twice as large as the
      experimental ones. Separate correlations in this paper of kappaT and of sigma
      with the cohesive energy density lead to kappaTsigma products that are
      commensurate with the experimental values for many of the molten salts, beyond
      the few 1:1 molten salts that have been dealt with previously. 

PMID- 24089789
TI  - Electronic structure and excited state dynamics in optically excited PTCDA films
      investigated with two-photon photoemission.
AB  - We present an investigation of the electronic structure and excited state
      dynamics of optically excited 3,4,9,10-perylene-tetracarboxylic acid dianhydride
      (PTCDA) thin films adsorbed on Ag(111) using two-photon photoemission
      spectroscopy (2PPE). 2PPE allows us to study both occupied and unoccupied
      electronic states, and we are able to identify signals from the highest occupied
      and the two lowest unoccupied electronic states of the PTCDA thin film in the
      2PPE spectra. The energies for occupied states are identical to values from
      ultraviolet photoelectron spectroscopy. Compared to results from inverse
      photoelectron spectroscopy (IPES), the 2PPE signals from the two lowest
      unoccupied electronic states, LUMO and LUMO+1, are found at 0.8 eV and 1.0 eV
      lower energies, respectively. We attribute this deviation to the different final
      states probed in 2PPE and IPES and the attractive interaction of the photoexcited
      electron and the remaining hole. Furthermore, we present a time-resolved
      investigation of the excited state dynamics of the PTCDA film in the femtosecond
      time regime. We observe a significantly shorter inelastic excited state lifetime
      compared to findings from time-resolved photoluminescence spectroscopy of PTCDA
      single crystals which could originate from excitation quenching by the metal
      substrate. 

PMID- 24089790
TI  - Effects of image charges on double layer structure and forces.
AB  - The study of the electrical double layer lies at the heart of soft matter physics
      and biophysics. Here, we address the effects of the image charges on the double
      layer structure and forces. For electrolyte solutions between two neutral plates,
      we show that depletion of the salt ions by the image charge repulsion results in
      short-range attractive and long-range repulsive forces. If cations and anions are
      of different valency, the asymmetric depletion leads to the formation of an
      induced electrical double layer. In comparison to a 1:1 electrolyte solution,
      both the attractive and the repulsive parts of the interaction are stronger for
      the 2:1 electrolyte solution. For two charged plates, the competition between the
      surface charge and the image charge effect can give rise to like-charge
      attraction and charge inversion. These results are in stark contrast with
      predictions from the Poisson-Boltzmann theory. 

PMID- 24089791
TI  - Estimation of diffusion anisotropy in microporous crystalline materials and
      optimization of crystal orientation in membranes.
AB  - The complex nature of the porous networks in microporous materials is primarily
      responsible for a high degree of intracrystalline diffusion anisotropy. Although
      this is a well-understood phenomenon, little attention has been paid in the
      literature with regards to classifying such anisotropy and elucidating its effect
      on the performance of membrane-based separation systems. In this paper, we
      develop a novel methodology to estimate full diffusion tensors based on the
      detailed description of the porous network geometry through our recent advances
      for the characterization of such networks. The proposed approach explicitly
      accounts for the tortuosity and complex connectivity of the porous framework, as
      well as for the variety of diffusion regimes that may be experienced by a guest
      molecule while it travels through the different localities of the crystal.
      Results on the diffusion of light gases in silicalite demonstrate good agreement
      with results from experiments and other computational techniques that have been
      reported in the literature. A comprehensive computational study involving 183
      zeolite frameworks classifies these structures in terms of a number of anisotropy
      metrics. Finally, we utilize the computed diffusion tensors in a membrane
      optimization model that determines optimal crystal orientations. Application of
      the model in the context of separating carbon dioxide from nitrogen demonstrates
      that optimizing crystal orientation can offer significant benefit to membrane
      based separation processes. 

PMID- 24089792
TI  - A first-principles study of ZnO polar surface growth: adsorption of Zn(x)O(y)
      clusters.
AB  - Adsorption of Zn(x)O(y) (x + y = 1-6) clusters on ZnO (000 +/- 1) polar surfaces
      is studied systematically via density function theory (DFT) calculations.
      Different adsorption behaviors are predicted for these two surfaces. On the
      (0001)-Zn surface, O atoms adsorb on hollow sites at the initial stage. Then Zn
      atoms come in, and the stable structure becomes bulk-like for some specific
      clusters. On the (0001)-O surface, Zn cluster adsorption leads to stable cage
      structures formed by pulling substrate O out. In clusters with both Zn and O, O
      atoms avoid directly bonding with the surface, and no energetically favorable
      bulk-like structure is found. On the basis of the prediction of these surface
      adsorption behaviors, experimentally observed growth rate and surface roughness
      differences on these two polar surfaces can be understood.

PMID- 24089793
TI  - Limiting diffusion current at rotating disk electrode with dense particle layer.
AB  - Exploiting the concept of diffusion permeability of multilayer gel membrane and
      porous multilayer we have derived a simple analytical equation for the limiting
      diffusion current at rotating disk electrode (RDE) covered by a thin layer with
      variable tortuosity and porosity, under the assumption of negligible convection
      in the porous film. The variation of limiting diffusion current with the porosity
      and tortuosity of the film can be described in terms of the equivalent thickness
      of stagnant solution layer, i.e., the average ratio of squared tortuosity to
      porosity. In case of monolayer of monodisperse spherical particles, the
      equivalent layer thickness is an algebraic function of the surface coverage.
      Thus, by means of cyclic voltammetry of RDE with a deposited particle monolayer
      we can determine the monolayer surface coverage. The effect of particle layer
      adsorbed on the surface of RDE increases non-linearly with surface coverage. We
      have tested our theoretical results experimentally by means of cyclic voltammetry
      measurements of limiting diffusion current at the glassy carbon RDE covered with
      a monolayer of 3 MUm silica particles. The theoretical and experimental results
      are in a good agreement at the surface coverage higher than 0.7. This result
      suggests that convection in a monolayer of 3 MUm monodisperse spherical particles
      is negligibly small, in the context of the coverage determination, in the range
      of very dense particle layers. 

PMID- 24089794
TI  - Dynamics of desorption with lateral diffusion.
AB  - The dynamics of desorption from a submonolayer of adsorbed atoms or ions are
      significantly influenced by the absence or presence of lateral diffusion of the
      adsorbed particles. When diffusion is present, the adsorbate configuration is
      simultaneously changed by two distinct processes, proceeding in parallel:
      adsorption/desorption, which changes the total adsorbate coverage, and lateral
      diffusion, which is coverage conserving. Inspired by experimental results, we
      here study the effects of these competing processes by kinetic Monte Carlo
      simulations of a simple lattice-gas model. In order to untangle the various
      effects, we perform large-scale simulations, in which we monitor coverage,
      correlation length, and cluster-size distributions, as well as the behavior of
      representative individual clusters, during desorption. For each initial adsorbate
      configuration, we perform multiple, independent simulations, without and with
      diffusion, respectively. We find that, compared to desorption without diffusion,
      the coverage-conserving diffusion process produces two competing effects: a
      retardation of the desorption rate, which is associated with a coarsening of the
      adsorbate configuration, and an acceleration due to desorption of monomers
      "evaporated" from the cluster perimeters. The balance between these two effects
      is governed by the structure of the adsorbate layer at the beginning of the
      desorption process. Deceleration and coarsening are predominant for
      configurations dominated by monomers and small clusters, while acceleration is
      predominant for configurations dominated by large clusters. 

PMID- 24089795
TI  - Study of intrinsic defects in 3C-SiC using first-principles calculation with a
      hybrid functional.
AB  - Density functional theory (DFT) with a tailored Hartree-Fock hybrid functional,
      which can overcome the band gap problem arising in conventional DFT and gives a
      valence band width comparable with experiment, is applied to determine formation
      energies and electronic structures of intrinsic defects in cubic silicon carbide
      (3C-SiC). Systematic comparison of defect formation energies obtained with the
      tailored hybrid functional and a conventional DFT functional clearly demonstrates
      that conventional DFT results are not satisfactory. The understanding on
      intrinsic defects, which were previously investigated mainly with conventional
      DFT functionals, is largely revised with regard to formation energies, electronic
      structures and transition levels. It is found that conventional DFT functionals
      basically lead to (i) underestimation of the formation energy when the defect
      charge is more negative and (ii) overestimation when the defect charge is more
      positive. The underestimation is mainly attributed to the well-known band gap
      problem. The overestimation is attributed to shrinkage of the valence bands,
      although in some cases such band shrinkage may lead to underestimation depending
      on how the defect alters the valence band structure. Both the band gap problem
      and the valence band shrinkage are often observed in semiconductors, including
      SiC, with conventional DFT functionals, and thus need to be carefully dealt with
      to achieve reliable computational results. 

PMID- 24089796
TI  - Adsorption of methylamine on mackinawite (FES) surfaces: a density functional
      theory study.
AB  - We have used density functional theory calculations to investigate the
      interaction between methylamine (CH3NH2) and the dominant surfaces of mackinawite
      (FeS), where the surface and adsorption properties of mackinawite have been
      characterized using the DFT-D2 method of Grimme. Our calculations show that while
      the CH3NH2 molecule only interacts weakly with the most stable FeS(001), it
      adsorbs relatively strongly on the FeS(011) and FeS(100) surfaces releasing
      energies of 1.26 eV and 1.51 eV, respectively. Analysis of the nature of the
      bonding reveals that the CH3NH2 molecule interacts with the mackinawite surfaces
      through the lone-pair of electrons located on the N atom. The electron density
      built up in the bonding region between N and Fe is very much what one would
      expect of covalent type of bonding. We observe no significant adsorption-induced
      changes of the FeS surface structures, suggesting that amine capping agents would
      not distort the FeS nanoparticle surfaces required for active heterogeneous
      catalytic reactions. The vibrational frequencies and the infrared spectra of
      adsorbed methylamine have been calculated and assignments for vibrational modes
      are used to propose a kinetic model for the desorption process, yielding a
      simulated temperature programmed desorption with a relative desorption
      temperature of <140 K at the FeS(011) surface and <170 K at FeS(100) surface. 

PMID- 24089797
TI  - Response of silicane and germanane to uni-axial compression: superstructures,
      polymorph nano-ribbons, and extreme bending.
AB  - Germanane (GeH) and silicane (SiH) are the fully hydrogenated forms of germanene
      and silicene, the Ge- and Si-analogues of graphene. Here we use density
      functional theory calculations to probe the properties of GeH and SiH sheets and
      their dependence on applied uni-axial compression. We find that GeH polymorphs
      with distinct hydrogen arrangements have markedly different energy band gaps. We
      also show that, when compressed, GeH forms superstructures with parts in low- and
      wide-gap geometries, enabling the creation of alternating polymorph nano-ribbons.
      An alternative to superstructure formation is the adoption by GeH of a corrugated
      form with extreme bending. Silicane shows similar behavior under compression,
      with either high corrugation, or successive parts with different geometries.
      Finally, we demonstrate that interaction with a substrate can influence the
      relative stability of GeH overlayer polymorphs. Overall, the results reveal ways
      to enhance the functionalities of these two-dimensional materials through the
      formation of superstructures with sizeable quantum well effects or outstanding
      mechanical response. 

PMID- 24089798
TI  - Dynamics in thermo-responsive nanogel crystals undergoing melting.
AB  - We report here the dynamics in thermo-responsive poly(N-isopropylacrylamide)
      (PNIPAM) nanogel crystals undergoing melting/freezing and verify the
      applicability of the dynamical criterion for melting/freezing proposed by Lowen
      et al. [Phys. Rev. Lett. 70, 1557 (1993)]. According to this criterion the ratio
      of long time diffusion coefficient (D(L)) to short time diffusion coefficients
      (D(S)) is ~0.1 for colloidal particles in suspension undergoing melting/freezing.
      Static and dynamic light scattering techniques have been employed to identify the
      melting/freezing transition of PNIPAM nanogel colloidal crystals of two different
      volume fractions phi = 0.49 and 0.79 and to measure D(L) and D(S) across the
      melting. In dense PNIPAM nanogel crystals undergoing melting, the ratio D(L)/D(S)
      is found to be less than 0.1 for the first time and this deviation is higher in
      the suspension with higher phi. We also show that the deviation is genuine by
      measuring D(L)/D(S) on shear melted charged silica colloidal liquid undergoing
      freezing. The mean square displacement at shorter times, close to the melting,
      shows subdiffusive behavior. The subdiffusive behavior, arising due to the
      overlap of the dangling polymer chains between shells of the neighboring
      particles, is argued to be the reason for the observed deviation.

PMID- 24089799
TI  - Sorption and diffusion of carbon dioxide and nitrogen in poly(methyl
      methacrylate).
AB  - Molecular dynamics simulations are performed to determine the solubility and
      diffusion coefficient of carbon dioxide and nitrogen in poly(methyl methacrylate)
      (PMMA). The solubilities of CO2 in the polymer are calculated employing our grand
      canonical ensemble simulation method, fixing the target excess chemical potential
      of CO2 in the polymer and varying the number of CO2 molecules in the polymer
      matrix till establishing equilibrium. It is shown that the calculated sorption
      isotherms of CO2 in PMMA, employing this method well agrees with experiment. Our
      results on the diffusion coefficients of CO2 and N2 in PMMA are shown to obey a
      common hopping mechanism. It is shown that the higher solubility of CO2 than that
      of N2 is a consequence of more attractive interactions between the carbonyl group
      of polymer and the sorbent. While the residence time of CO2 beside the carbonyl
      group of polymer is about three times higher than that of N2, the diffusion
      coefficient of CO2 in PMMA is higher than that of N2. The higher diffusion
      coefficient of CO2, compared to N2, in PMMA is shown to be due to the higher (~3
      times) swelling of polymer upon CO2 uptake. 

PMID- 24089800
TI  - Effect of temperature gradient on liquid-liquid phase separation in a polyolefin
      blend.
AB  - We have investigated experimentally the structure formation processes during
      phase separation via spinodal decomposition above and below the spinodal line in
      a binary polymer blend system exposed to in-plane stationary thermal gradients
      using phase contrast optical microscopy and temperature gradient hot stage. Below
      the spinodal line there is a coupling of concentration fluctuations and thermal
      gradient imposed by the temperature gradient hot stage. Also under the thermal
      gradient annealing phase-separated domains grow faster compared with the system
      under homogeneous temperature annealing on a zero-gradient or a conventional hot
      stage. We suggest that the in-plane thermal gradient accelerates phase separation
      through the enhancement in concentration fluctuations in the early and
      intermediate stages of spinodal decomposition. In a thermal gradient field, the
      strength of concentration fluctuation close to the critical point (above the
      spinodal line) is strong enough to induce phase separation even in one-phase
      regime of the phase diagram. In the presence of a temperature gradient the
      equilibrium phase diagrams are no longer valid, and the systems with an upper
      critical solution temperature can be quenched into phase separation by applying
      the stationary temperature gradient. The in-plane temperature gradient drives
      enhanced concentration fluctuations in a binary polymer blend system above and
      below the spinodal line. 

PMID- 24089801
TI  - Side-chain effects on the solution-phase conformations and charge photogeneration
      dynamics of low-bandgap copolymers.
AB  - Solution-phase conformations and charge photogeneration dynamics of a pair of low
      bandgap copolymers based on benzo[1,2-b:4,5-b(')]dithiophene (BDT) and thieno[3,4
      b]thiophene (TT), differed by the respective carbonyl (-C) and ester (-E)
      substituents at the TT units, were comparatively investigated by using near
      infrared time-resolved absorption (TA) spectroscopy at 25  degrees C and 120 
      degrees C. Steady-state and TA spectroscopic results corroborated by quantum
      chemical analyses prove that both PBDTTT-C and PBDTTT-E in chlorobenzene
      solutions are self-aggregated; however, the former bears a relatively higher
      packing order. Specifically, PBDTTT-C aggregates with more pi-pi stacked domains,
      whereas PBDTTT-E does with more random coils interacting strongly at the chain
      intersections. At 25  degrees C, the copolymers exhibit comparable exciton
      lifetimes (~1 ns) and fluorescence quantum yields (~2%), but distinctly different
      charge photogeneration dynamics: PBDTTT-C on photoexcitation gives rise to a
      branching ratio of charge separated (CS) over charge transfer (CT) states more
      than 20% higher than PBDTTT-E does, correlating with their photovoltaic
      performance. Temperature and excitation-wavelength dependent exciton/charge
      dynamics suggest that the CT states localize at the chain intersections that are
      survivable up to 120  degrees C, and that the excitons and the CS states inhabit
      the stretched strands and the also thermally robust orderly stacked domains. The
      stable self-aggregation structures and the associated primary charge dynamics of
      the PBDTTT copolymers in solutions are suggested to impact intimately on the
      morphologies and the charge photogeneration efficiency of the solid-state
      photoactive layers.

PMID- 24089802
TI  - Investigation of the effect of bilayer membrane structures and fluctuation
      amplitudes on SANS/SAXS profile for short membrane wavelength.
AB  - The effect of bilayer membrane structures and fluctuation amplitudes on small
      angle neutron scattering (SANS) and small angle X-ray scattering (SAXS) profile
      is investigated based on harmonic motions of the surfactant bilayers with bending
      as well as thickness fluctuation motions. In this study we consider the case in
      which the wavelength of the bilayer membrane is shorter than the thickness of the
      membrane. We find that the thickness of the surfactant bilayer membrane, d(m),
      affects both q(dip) and q(peak) of I(q,0) profile, and that the fluctuation
      amplitude, a, of the membrane changes the peak of I(q,0). A simple formula is
      derived to estimate the thickness of the bilayer based on the q(dip) of the
      profile obtained from the simulation. The resulting estimates of the thickness of
      the bilayer with harmonic motion showed accuracy within 1%. Moreover, the bilayer
      thicknesses estimated from the proposed formula show an excellent agreement with
      the SANS and SAXS experimental results available in the literatures. We also
      propose a curve fit model, which describes the relationship between the
      fluctuation amplitude and the normalized q(peak) ratio. The present results show
      the feasibility of the simple formula to estimate the fluctuation amplitude based
      on the SANS and SAXS profiles.

PMID- 24089803
TI  - Effective potentials for representing polymers in melts as chains of interacting
      soft particles.
AB  - This paper outlines the derivation of an analytical pair potential in a coarse
      grained description of polymer melts where each chain is represented as a
      collection of soft spheres. Each particle is located at the center of mass of a
      polymer subchain, while the polymer is divided into an arbitrary number of
      identical chain subsections, each comprised of a large number of monomers. It is
      demonstrated that the soft effective pair potentials acting between these center
      of-mass sites is described by a soft repulsive region at separation distances
      less than the average size of each coarse grained unit and a long repulsive tail,
      with a small attractive component. The attractive component is located at a
      length scale beyond the size of the coarse grained unit and its form varies with
      the level of interpenetration between the coarse-grained units. Consistent with
      numerically derived potentials, it is found that the short range features of the
      potential dominate the liquid structure, while the long-tail features dominate
      the virial-route thermodynamics of the system. It follows that the accurate
      determination of the effective potential in both short and large separation
      distances is relevant for ensuring structural and thermodynamic consistency in
      the coarse-grained description of the macromolecular liquid. It is further shown
      that due to the sensitivity of thermodynamic properties to the large-scale
      features of the potential, which are irrelevant to the reproducibility of
      structural correlations, the determination of thermodynamically accurate
      potentials by numerical optimization of structure alone is not a reliable
      strategy in the high-density regime for high levels of coarse-graining. 

PMID- 24089804
TI  - Fluctuation/correlation effects in symmetric diblock copolymers: on the order
      disorder transition.
AB  - Using fast off-lattice Monte Carlo simulations with experimentally accessible
      fluctuations, we reported the first systematic study unambiguously quantifying
      the shift of the order-disorder transition (ODT) chi* of symmetric diblock
      copolymers from the mean-field prediction chi(MF)*. Our simulations are performed
      in a canonical ensemble with variable box lengths to eliminate the restriction of
      periodic boundary conditions on the lamellar period, and give the most accurate
      data of chi* and bulk lamellar period reported to date. Exactly the same model
      system (Hamiltonian) is used in both our simulations and mean-field theory; the
      ODT shift is therefore due to the fluctuations/correlations neglected by the
      latter. While chi*/chi(MF)*-1?N(-k) is found with N denoting the invariant degree
      of polymerization, k decreases around the N-value corresponding to the face
      centered cubic close packing of polymer segments as hard spheres, indicating the
      short-range correlation effects.

PMID- 24089805
TI  - Phase behavior of hard spherical caps.
AB  - This work reports on the phase behavior of hard spherical caps in the interval of
      particle shapes delimited by the hard platelet and hemispherical cap models.
      These very simple model colloidal particles display a remarkably complex phase
      behavior featuring a competition between isotropic-nematic phase separation and
      clustering as well as a sequence of structures, from roundish to lacy aggregates
      to no ordinary hexagonal columnar mesophases, all characterized by groups of
      particles tending to arrange on the same spherical surface. This behavior
      parallels that one of many molecular systems forming micelles but here it is
      purely entropy-driven. 

PMID- 24089806
TI  - Fluctuations of systems in finite heat reservoirs with applications to phase
      transitions in lipid membranes.
AB  - In an adiabatically shielded system, the total enthalpy is conserved. Enthalpy
      fluctuations of an arbitrarily chosen subsystem must be buffered by the remainder
      of the total system which serves as a heat reservoir. The magnitude of these
      fluctuations depends on the size of the reservoir. This leads to various
      interesting consequences for the physical behavior of the subsystem. As an
      example, we treat a lipid membrane with a phase transition that is embedded in an
      aqueous reservoir. We find that large fluctuations are attenuated when the
      reservoir has finite size. This has consequences for the compressibility of the
      membrane since volume and area fluctuations are also attenuated. We compare the
      equilibrium fluctuations of subsystems in finite reservoirs with those in
      periodically driven systems. In such systems, the subsystem has only finite time
      available to exchange heat with the surrounding medium. A larger frequency
      therefore reduces the volume of the accessible heat reservoir. Consequently, the
      fluctuations of the subsystem display a frequency dependence. While this work is
      of particular interest for a subsystem displaying a transition such as a lipid
      membrane, some of the results are of a generic nature and may contribute to a
      better understanding of relaxation processes in general. 

PMID- 24089807
TI  - Charge transport in desolvated DNA.
AB  - The conductivity of DNA in molecular junctions is often probed experimentally
      under dry conditions, but it is unclear how much of the solvent remains attached
      to the DNA and how this impacts its structure, electronic states, and
      conductivity. Classical MD simulations show that DNA is unstable if the solvent
      is removed completely, while a micro-hydrated system with few water molecules
      shows similar charge transport properties as fully solvated DNA does. This
      surprising effect is analyzed in detail by mapping the density functional theory
      based electronic structure to a tight-binding Hamiltonian, allowing for an
      estimate of conductivity of various DNA sequences with snapshot-averaged
      Landauer's approach. The characteristics of DNA charge transport turn out to be
      determined by the nearest hydration shell(s), and the removal of bulk solvent has
      little effect on the transport. 

PMID- 24089808
TI  - Comment on "The application of the thermodynamic perturbation theory to study the
      hydrophobic hydration" [J. Chem. Phys. 139, 024101 (2013)].

PMID- 24089810
TI  - A new, low temperature long-pass cell for mid-infrared to terahertz spectroscopy
      and synchrotron radiation use.
AB  - A new cell has been designed for accurate spectroscopic measurements in the 80
      400 K temperature range with variable path lengths from 3 to more than 141 m. The
      spectral coverage at these temperatures ranges from the visible to less than 10
      cm(-1), thanks to the use of diamond windows. The design of the cryostat and
      vacuum setups allows vibration-free operation. The equipment provides temperature
      homogeneity and pressure control to better than 2% over the 100-400 K and the 0.1
      1000 mbar ranges. Remote-controlled opto-mechanical systems enable in situ
      adjustments as well as changes of the optical path length within half an hour, in
      order to optimize measurement time in an open user facility. It allows then to
      meet the specific requirements of high resolution measurements on the Far
      Infrared AILES beamline at SOLEIL as well at the LISA facility, in Creteil, in
      the mid-IR. This new instrument opens up the way for many experiments in the
      field of high-resolution gas-phase IR spectroscopy, in particular, in
      quantitative spectroscopy for atmospheric applications: measurements of
      absorption line parameters (absolute intensities, cross sections, and pressure
      induced widths) using Fourier transform spectroscopy. The design and performance
      of the equipment are briefly presented and illustrated on spectroscopic examples.

PMID- 24089811
TI  - Optical emission spectroscopy at the large RF driven negative ion test facility
      ELISE: instrumental setup and first results.
AB  - One of the main topics to be investigated at the recently launched large
      (A(source) = 1.0 * 0.9 m(2)) ITER relevant RF driven negative ion test facility
      ELISE (Extraction from a Large Ion Source Experiment) is the connection between
      the homogeneity of the plasma parameters close to the extraction system and the
      homogeneity of the extracted negative hydrogen ion beam. While several
      diagnostics techniques are available for measuring the beam homogeneity, the
      plasma parameters are determined by optical emission spectroscopy (OES) solely.
      First OES measurements close to the extraction system show that without magnetic
      filter field the vertical profile of the plasma emission is more or less
      symmetric, with maxima of the emission representing the projection of the plasma
      generation volumes, and a distinct minimum in between. The profile changes with
      the strength of the magnetic filter field but under all circumstances the plasma
      emission in ELISE is much more homogeneous compared to the smaller IPP prototype
      sources. Planned after this successful demonstration of the ELISE OES system is
      to combine OES with tomography in order to determine locally resolved values for
      the plasma parameters.

PMID- 24089812
TI  - Ultrafast x-ray photoelectron spectroscopy in the microsecond time domain.
AB  - We introduce a new approach for ultrafast in situ high-resolution X-ray
      photoelectron spectroscopy (XPS) to study surface processes and reaction kinetics
      on the microsecond timescale. The main idea is to follow the intensity at a fixed
      binding energy using a commercial 7 channeltron electron analyzer with a modified
      signal processing setup. This concept allows for flexible switching between
      measuring conventional XP spectra and ultrafast XPS. The experimental
      modifications are described in detail. As an example, we present measurements for
      the adsorption and desorption of CO on Pt(111), performed at the synchrotron
      radiation facility BESSY II, with a time resolution of 500 MUs. Due to the
      ultrafast measurements, we are able to follow adsorption and desorption in situ
      at pressures of 2 * 10(-6) mbar and temperatures up to 500 K. The data are
      consistently analyzed using a simple model in line with data obtained with
      conventional fast XPS at temperatures below 460 K. Technically, our new approach
      allows measurement on even shorter timescales, down to 20 MUs. 

PMID- 24089813
TI  - High-resolution Laue-type DuMond curved crystal spectrometer.
AB  - We report on a high-resolution transmission-type curved crystal spectrometer
      based on the modified DuMond slit geometry. The spectrometer was developed at the
      University of Fribourg for the study of photoinduced X-ray spectra. K and L X-ray
      transitions with energies above about 10 keV can be measured with an instrumental
      resolution comparable to their natural linewidths. Construction details and
      operational characteristics of the spectrometer are presented. The variation of
      the energy resolution as a function of the focal distance and diffraction order
      is discussed. The high sensitivity of the spectrometer is demonstrated via the 2s
      1s dipole-forbidden X-ray transition of Gd which could be observed despite its
      extremely low intensity. The precision of the instrument is illustrated by
      comparing the sum of the energies of the Au K-L2 and L2-M3 cascading transitions
      with the energy of the crossover K-M3 transition as well as by considering the
      energy differences of the Gd Kalpha1 X-ray line measured at five different
      diffraction orders. Finally, to demonstrate the versatility of the spectrometer,
      it is shown that the latter can also be used for in-house extended X-ray
      absorption fine structure measurements. 

PMID- 24089814
TI  - An atom trap trace analysis system for measuring krypton contamination in xenon
      dark matter detectors.
AB  - We have developed an atom trap trace analysis (ATTA) system to measure Kr in Xe
      at the part per trillion (ppt) level, a prerequisite for the sensitivity
      achievable with liquid xenon dark matter detectors beyond the current generation.
      Since Ar and Kr have similar laser cooling wavelengths, the apparatus has been
      tested with Ar to avoid contamination prior to measuring Xe samples. A radio
      frequency plasma discharge generates a beam of metastable atoms which is
      optically collimated, slowed, and trapped using standard magneto-optical
      techniques. Based on the measured overall system efficiency of 1.2 * 10(-8)
      (detection mode), we expect the ATTA system to reach the design goal sensitivity
      to ppt concentrations of Kr in Xe in <2 h. 

PMID- 24089815
TI  - Nanopatterning and tuning of optical taper antenna apex for tip-enhanced Raman
      scattering performance.
AB  - This paper focuses on finding optimal electrochemical conditions from linear
      sweep voltammetry analysis for preparing highly reproducible tip-enhanced Raman
      scattering (TERS) conical gold tips with dc-pulsed voltage etching. Special
      attention is given to the reproducibility of tip apex shapes with different
      etchant mixtures. We show that the fractional Brownian motion model enables a
      mathematical description of the decaying current kinetics during the whole
      etching process up to the cutoff event. Further progress in preparation of highly
      reproducible smooth and sharp tip apexes is related to the effect of an additive,
      such as isopropanol, to aqueous acids. A finite-difference time-domain method
      based near-field analysis provides evidence that TERS performance depends
      critically on tip orientation relative to a highly focused laser beam. A TERS
      based criterion for recognizing gold tips able to couple/decouple optical near-
      and far-fields is proposed. 

PMID- 24089816
TI  - Discharge tube with coaxial geometry for efficient production of metal hydrides.
AB  - The production of metal hydrides in vapour phase is one of the problems which
      makes their spectroscopic investigation at high resolution difficult. The
      molecular densities are usually low and the absorption is often increased by the
      use of multipass cells or intracavity setups. In this contribution a discharge
      tube with coaxial geometry is investigated, which is able to produce relatively
      high densities of NiH (~10(12) cm(-3)). Additional advantage of the present
      geometry is that the densities are very homogeneous along the discharge length,
      250 mm in our case, which can be made in principle arbitrary long. As a result,
      reliable absorption was detected even in a single pass experiment. We also
      present the results of a numerical model which explains the general properties of
      the plasma in the tube. Based on this understanding, we discuss possible
      improvements and other applications of this discharge geometry. 

PMID- 24089817
TI  - Temperature and density evolution during decay in a 2.45 GHz hydrogen electron
      cyclotron resonance plasma: off-resonant and resonant cases.
AB  - Time resolved electron temperature and density measurements during the decay
      stage in a hydrogen electron cyclotron resonance (ECR) plasma are presented for a
      resonance and off-resonance magnetic field configurations. The measurements are
      conducted on a ECR plasma generator excited at 2.45 GHz denominated test-bench
      for ion-sources plasma studies at ESS Bilbao. The plasma parameters evolution is
      studied by Langmuir probe diagnostic with synchronized sample technique developed
      for repetitive pulsed plasmas with a temporal resolution of 200 ns in typical
      decay processes of about 40 MUs. An afterglow transient is clearly observed in
      the reflected microwave power signal from the plasma. Simultaneously, the
      electron temperature evolution shows rebounding peaks that may be related to the
      interplay between density drop and microwave coupling with deep impact on the
      Electron Energy Distribution Function. The correlation of such structures with
      the plasma absorbed power and the coupling quality is also reported. 

PMID- 24089818
TI  - Propagation and stability characteristics of a 500-m-long laser-based fiducial
      line for high-precision alignment of long-distance linear accelerators.
AB  - A laser-based alignment system with a He-Ne laser has been newly developed in
      order to precisely align accelerator units at the KEKB injector linac. The laser
      beam was first implemented as a 500-m-long fiducial straight line for alignment
      measurements. We experimentally investigated the propagation and stability
      characteristics of the laser beam passing through laser pipes in vacuum. The
      pointing stability at the last fiducial point was successfully obtained with the
      transverse displacements of +/-40 MUm level in one standard deviation by applying
      a feedback control. This pointing stability corresponds to an angle of +/-0.08
      MUrad. This report contains a detailed description of the experimental
      investigation for the propagation and stability characteristics of the laser beam
      in the laser-based alignment system for long-distance linear accelerators. 

PMID- 24089819
TI  - A free jet (supersonic), molecular beam source with automatized, 50 nm precision
      nozzle-skimmer positioning.
AB  - Low energy (thermal) free jet (supersonic) molecular beams are used in a range of
      applications from surface science and surface deposition to quantum coherence and
      gas kinetics experiments. A free jet molecular beam is created by a gas expansion
      from a high pressure reservoir through a small aperture (nozzle). The nozzle
      typically has a diameter of 2-20 MUm. The central part of the beam is selected
      using a skimmer, typically up to 500 MUm in diameter. Recent years have seen the
      introduction of highly spatially confined beam sources based on micrometer
      skimmers and micrometer or even sub-micrometer nozzles. Such sources have been
      applied, for example, in the investigation of superfluidity and in neutral helium
      microscopy. However, up till now no source design allowing the precise
      positioning of the micro-skimmer relative to the nozzle has been available. This
      is an important issue because the relative position of skimmer and nozzle can
      influence the beam properties considerably. Here we present the design and
      implementation of a new molecular beam source, which allows an automatized, 50 nm
      precision positioning of the skimmer relative to the nozzle. The source is liquid
      nitrogen cooled and the temperature can be controlled between 110 K and 350 K
      with a temperature fluctuation of less than +/-0.1 K over several hours. Beam
      intensity measurements using a 5 MUm nozzle and a skimmer 5 MUm in diameter are
      presented for stagnation pressures po in the range 3-180 bars. A 2D beam profile
      scan, using a 9.5 MUm skimmer and a 5 MUm nozzle is presented as a further
      documentation of the versatility of the new design and as an illustration of the
      influence of the relative skimmer-nozzle position on the beam properties.

PMID- 24089820
TI  - The effect of the H2 density on the electron energy distribution in H- ion
      sources.
AB  - The electron energy distribution in H(-) ion sources is studied. By three
      dimensional Monte Carlo simulations (3D-MCC) and cross sections of collisions,
      the crucial collisions in the JAEA 10A are chosen to develop theoretical models
      for the low electron temperature and the high electron temperature, respectively.
      The effects of the H2 density on the low electron temperature and the high
      electron temperature in H(-) ion sources are predicted with analytic expressions
      and verified by 3D-MCC. The results show that both the low and high electron
      temperatures become lower while n(H2) increases.

PMID- 24089821
TI  - High-resolution mass spectrometer for liquid metal ion sources.
AB  - Recently, a mass spectrometer for liquid metal ion sources (LMIS) has been built
      and set into operation. This device uses an E * B-filter as mass dispersive
      element and provides sufficient resolution to analyse the emission of clusters
      from LMIS to much higher mass ranges (>2000 amu) than commercially available mass
      filters for focused ion beam systems. It has also been shown that for small
      masses the composition of clusters from different isotopes can be resolved.
      Furthermore, a rather high fluence of monodisperse clusters in the range of 10(6)
      10(7) clusters/s can be achieved with this setup. This makes it a promising tool
      for the preparation of mass selected clusters. In this contribution, theoretical
      considerations as well as technical details and the results of first measurements
      are presented. 

PMID- 24089822
TI  - An all solid-state high-voltage ns trigger generator based on magnetic pulse
      compression and transmission line transformer.
AB  - Innovative design of an all solid-state high-voltage ns trigger generator, based
      on magnetic pulse compression and transmission line transformer, is presented.
      The repetitive trigger pulse generator was developed to trigger a 700 kV
      trigatron, which has been used to pulse a repetitive intense electron beam
      accelerator with Tesla transformer charged double pulse forming lines (PFLs).
      Experimental results show that the trigger pulse generator could produce 180 kV
      65 ns duration pulses with a rise time of 20 ns. The repetitive trigger pulses
      have nice uniform in the voltage waveform. The control time jitter is less then 3
      ns. Owing to its good stability and low time jitter, the high-voltage trigger
      generator is an excellent candidate to trigger the repetitive accelerator. 

PMID- 24089823
TI  - A multichannel magnetic probe system for analysing magnetic fluctuations in
      helical axis plasmas.
AB  - The need to understand the structure of magnetic fluctuations in H-1NF heliac [S.
      Hamberger et al., Fusion Technol. 17, 123 (1990)] plasmas has motivated the
      installation of a sixteen former, tri-axis helical magnetic probe Mirnov array
      (HMA). The new array complements two existing poloidal Mirnov arrays by providing
      polarisation information, higher frequency response, and improved toroidal
      resolution. The helical placement is ideal for helical axis plasmas because it
      positions the array as close as possible to the plasma in regions of varying
      degrees of favourable curvature in the magnetohydrodynamic sense, but almost
      constant magnetic angle. This makes phase variation with probe position near
      linear, greatly simplifying the analysis of the data. Several of the issues
      involved in the design, installation, data analysis, and calibration of this
      unique array are presented including probe coil design, frequency response
      measurements, mode number identification, orientation calculations, and mapping
      probe coil positions to magnetic coordinates. Details of specially designed
      digitally programmable pre-amplifiers, which allow gains and filters to be
      changed as part of the data acquisition initialisation sequence and stored with
      the probe signals, are also presented. The low shear heliac geometry [R. Jimenez
      Gomez et al., Nucl. Fusion 51, 033001 (2011)], flexibility of the H-1NF heliac,
      and wealth of information provided by the HMA create a unique opportunity for
      detailed study of Alfven eigenmodes, which could be a serious issue for future
      fusion reactors.

PMID- 24089824
TI  - CO2 laser-based dispersion interferometer utilizing orientation-patterned gallium
      arsenide for plasma density measurements.
AB  - A dispersion interferometer based on the second-harmonic generation of a carbon
      dioxide laser in orientation-patterned gallium arsenide has been developed for
      measuring electron density in plasmas. The interferometer includes two nonlinear
      optical crystals placed on opposite sides of the plasma. This instrument has been
      used to measure electron line densities in a pulsed radio-frequency generated
      argon plasma. A simple phase-extraction technique based on combining measurements
      from two successive pulses of the plasma has been used. The noise-equivalent line
      density was measured to be 1.7 * 10(17) m(-2) in a detection bandwidth of 950
      kHz. One of the orientation-patterned crystals produced 13 mW of peak power at
      the second-harmonic wavelength from a carbon dioxide laser with 13 W of peak
      power. Two crystals arranged sequentially produced 58 mW of peak power at the
      second-harmonic wavelength from a carbon dioxide laser with 37 W of peak power. 

PMID- 24089825
TI  - Minimum Fisher regularization of image reconstruction for infrared imaging
      bolometer on HL-2A.
AB  - An infrared imaging bolometer diagnostic has been developed recently for the HL
      2A tokamak to measure the temporal and spatial distribution of plasma radiation.
      The three-dimensional tomography, reduced to a two-dimensional problem by the
      assumption of plasma radiation toroidal symmetry, has been performed. A three
      dimensional geometry matrix is calculated with the one-dimensional pencil beam
      approximation. The solid angles viewed by the detector elements are taken into
      account in defining the chord brightness. And the local plasma emission is
      obtained by inverting the measured brightness with the minimum Fisher
      regularization method. A typical HL-2A plasma radiation model was chosen to
      optimize a regularization parameter on the criterion of generalized cross
      validation. Finally, this method was applied to HL-2A experiments, demonstrating
      the plasma radiated power density distribution in limiter and divertor
      discharges. 

PMID- 24089826
TI  - The circuit of polychromator for Experimental Advanced Superconducting Tokamak
      edge Thomson scattering diagnostic.
AB  - The detector circuit is the core component of filter polychromator which is used
      for scattering light analysis in Thomson scattering diagnostic, and is
      responsible for the precision and stability of a system. High signal-to-noise and
      stability are primary requirements for the diagnostic. Recently, an upgraded
      detector circuit for weak light detecting in Experimental Advanced
      Superconducting Tokamak (EAST) edge Thomson scattering system has been designed,
      which can be used for the measurement of large electron temperature (T(e))
      gradient and low electron density (n(e)). In this new circuit, a thermoelectric
      cooled avalanche photodiode with the aid circuit is involved for increasing
      stability and enhancing signal-to-noise ratio (SNR), especially the circuit will
      never be influenced by ambient temperature. These features are expected to
      improve the accuracy of EAST Thomson diagnostic dramatically. Related mechanical
      construction of the circuit is redesigned as well for heat-sinking and
      installation. All parameters are optimized, and SNR is dramatically improved. The
      number of minimum detectable photons is only 10.

PMID- 24089827
TI  - Optical designs of reflection and refraction collection optics for a JT-60SA core
      Thomson scattering system.
AB  - Collection optics for core measurements in a JT-60SA Thomson scattering system
      were designed. The collection optics will be installed in a limited space and
      have a wide field of view and wide wavelength range. Two types of the optics are
      therefore suggested: refraction and reflection types. The reflection system, with
      a large primary mirror, avoids large chromatic aberrations. Because the size
      limit of the primary mirror and vignetting due to the secondary mirror affect the
      total collection throughput, conditions that provide the high throughput are
      found through an optimization. A refraction system with four lenses forming an
      Ernostar system is also employed. The use of high-refractive-index glass
      materials enhances the freedom of the lens curvatures, resulting in suppression
      of the spherical and coma aberration. Moreover, sufficient throughput can be
      achieved, even with smaller lenses than that of a previous design given in [H.
      Tojo, T. Hatae, T. Sakuma, T. Hamano, K. Itami, Y. Aida, S. Suitoh, and D. Fujie,
      Rev. Sci. Instrum. 81, 10D539 (2010)]. The optical resolutions of the reflection
      and refraction systems are both sufficient for understanding the spatial
      structures in plasma. In particular, the spot sizes at the image of the optics
      are evaluated as ~0.3 mm and ~0.4 mm, respectively. The throughput for the two
      systems, including the pupil size and transmissivity, are also compared. The
      results show that good measurement accuracy (<10%) even at high electron
      temperatures (<30 keV) can be expected in the refraction system.

PMID- 24089828
TI  - Low background high efficiency radiocesium detection system based on positron
      emission tomography technology.
AB  - After the 2011 nuclear power plant accident at Fukushima, radiocesium
      contamination in food became a serious concern in Japan. However, low background
      and high efficiency radiocesium detectors are expensive and huge, including
      semiconductor germanium detectors. To solve this problem, we developed a
      radiocesium detector by employing positron emission tomography (PET) technology.
      Because (134)Cs emits two gamma photons (795 and 605 keV) within 5 ps, they can
      selectively be measured with coincidence. Such major environmental gamma photons
      as (40)K (1.46 MeV) are single photon emitters and a coincidence measurement
      reduces the detection limit of radiocesium detectors. We arranged eight sets of
      Bi4Ge3O12 (BGO) scintillation detectors in double rings (four for each ring) and
      measured the coincidence between these detectors using PET data acquisition
      system. A 50 * 50 * 30 mm BGO was optically coupled to a 2 in. square
      photomultiplier tube (PMT). By measuring the coincidence, we eliminated most
      single gamma photons from the energy distribution and only detected those from
      (134)Cs at an average efficiency of 12%. The minimum detectable concentration of
      the system for the 100 s acquisition time is less than half of the food monitor
      requirements in Japan (25 Bq/kg). These results show that the developed
      radiocesium detector based on PET technology is promising to detect low level
      radiocesium.

PMID- 24089829
TI  - Deconvolving the temporal response of photoelectric x-ray detectors for the
      diagnosis of pulsed radiations.
AB  - Based on the conjugate gradient method, a simple algorithm is presented for
      deconvolving the temporal response of photoelectric x-ray detectors (XRDs) to
      reconstruct the resolved time-dependent x-ray fluxes. With this algorithm, we
      have studied the impact of temporal response of XRD on the radiation diagnosis of
      hohlraum heated by a short intense laser pulse. It is found that the limiting
      temporal response of XRD not only postpones the rising edge and peak position of
      x-ray pulses but also smoothes the possible fluctuations of radiation fluxes.
      Without a proper consideration of the temporal response of XRD, the measured
      radiation flux can be largely misinterpreted for radiation pulses of a hohlraum
      heated by short or shaped laser pulses. 

PMID- 24089830
TI  - The autofocusing system of the IMAT neutron camera.
AB  - In this paper, we present the autofocusing system of the imaging instrument to be
      used on IMAT, a new neutron-imaging facility under construction at the ISIS (UK)
      target station 2. We have compared 16 different autofocus algorithms to select
      the one with the best performance. The algorithms have been evaluated by using
      both a qualitative analysis and a quantitative one. An overall score has been
      computed and the "contrast based" algorithm has been selected for the
      autofocusing system. The adopted setup together with the described autofocusing
      system makes the camera a user-friendly imaging device allowing the optimization
      of beam time use. 

PMID- 24089831
TI  - Quantitative scanning thermal microscopy based on determination of thermal probe
      dynamic resistance.
AB  - Resistive thermal probes used in scanning thermal microscopy provide high spatial
      resolution of measurement accompanied with high sensitivity to temperature
      changes. At the same time their sensitivity to variations of thermal conductivity
      of a sample is relatively low. In typical dc operation mode the static resistance
      of the thermal probe is measured. It is shown both analytically and
      experimentally that the sensitivity of measurement can be improved by a factor of
      three by measuring the dynamic resistance of a dc biased probe superimposed with
      small ac current. The dynamic resistance can be treated as a complex value. Its
      amplitude represents the slope of the static voltage-current U-I characteristic
      for a given I while its phase describes the delay between the measured ac voltage
      and applied ac current component in the probe. The phase signal also reveals
      dependence on the sample thermal conductivity. Signal changes are relatively
      small but very repeatable. In contrast, the difference between dynamic and static
      resistance has higher sensitivity (the same maximum value as that of the 2nd and
      3rd harmonics), and also much higher amplitude than higher harmonics. The
      proposed dc + ac excitation scheme combines the benefits of dc excitation
      (mechanical stability of probe-sample contact, average temperature control) with
      those of ac excitation (base-line stability, rejection of ambient temperature
      influence, high sensitivity, lock-in signal processing), when the experimental
      conditions prohibit large ac excitation. 

PMID- 24089832
TI  - Prevention of cartilage dehydration in imaging studies with a customized humidity
      chamber.
AB  - Quantitative three-dimensional imaging methods such as micro-computed tomography
      (MUCT) allow for the rapid and comprehensive evaluation of cartilage and bone in
      animal models, which can be used for drug development and related research in
      arthritis. However, when imaging fresh cartilage tissue in air, a common problem
      is tissue dehydration which causes movement artifact in the resulting images.
      These artifacts distort scans and can render them unusable, leading to a
      considerable loss of time and effort with sample preparation and measurement. The
      sample itself is also irretrievably damaged by the dehydration, often unable to
      return to its full tissue thickness upon rehydration. Additionally, imaging with
      ionic contrast agents such as Hexabrix(TM) must be performed in air, otherwise
      the agent will be washed out if immersed in a liquid. The first goal of this
      study was to design a customized humidity chamber to maintain cartilage hydration
      without the need for immersion. Following this, the use of the humidity chamber
      during a synchrotron radiation-MUCT scan was validated and its performance
      evaluated. Results showed that the loss of fluid film volume is associated with
      scanning at low humidity (87%), and can be avoided using the humidity chamber.
      Coupling this technology with advances in synchrotron imaging (e.g., phase
      contrast imaging) or contrast agents is promising. 

PMID- 24089833
TI  - Spatial filtering nearly eliminates the side-lobes in single- and multi-photon
      4pi-type-C super-resolution fluorescence microscopy.
AB  - Super-resolution microscopy has tremendously progressed our understanding of
      cellular biophysics and biochemistry. Specifically, 4pi fluorescence microscopy
      technique stands out because of its axial super-resolution capability. All types
      of 4pi-microscopy techniques work well in conjugation with deconvolution
      techniques to get rid of artifacts due to side-lobes. In this regard, we propose
      a technique based on spatial filter in a 4pi-type-C confocal setup to get rid of
      these artifacts. Using a special spatial filter, we have reduced the depth-of
      focus. Interference of two similar depth-of-focus beams in a 4pi geometry result
      in substantial reduction of side-lobes. Studies show a reduction of side-lobes by
      46% and 76% for single and two photon variant compared to 4pi - type - C confocal
      system. This is incredible considering the resolving capability of the existing
      4pi - type - C confocal microscopy. Moreover, the main lobe is found to be 150 nm
      for the proposed spatial filtering technique as compared to 690 nm of the state
      of-art confocal system. Reconstruction of experimentally obtained 2PE - 4pi data
      of green fluorescent protein (GFP)-tagged mitocondrial network shows near
      elimination of artifacts arising out of side-lobes. Proposed technique may find
      interesting application in fluorescence microscopy, nano-lithography, and cell
      biology. 

PMID- 24089835
TI  - Generalization of the classical xyz-polarization analysis technique to out-of
      plane and inelastic scattering.
AB  - The technique of longitudinal ("xyz") polarization analysis has been used
      successfully for many years to study disordered magnetic materials in thermal and
      cold neutron diffraction experiments. The technique allows the simultaneous and
      unambiguous separation of the nuclear, magnetic, and nuclear spin-incoherent
      contributions to the scattering. The technical advances seen in recent years,
      such as the availability of polarized (3)He analyzer cells to cover a large
      detector solid angle, the ability to detect out-of-plane scattering in a multi
      detector, and a significant increase of the usable beam divergence, call for a
      generalization of the method. A general treatment of the formalism for carrying
      out neutron polarization analysis will be given in this paper, which describes a
      possible method of usage at a future, modern diffractometer or inelastic
      spectrometer with large area multi-detector coverage. 

PMID- 24089834
TI  - KOTOBUKI-1 apparatus for cryogenic coherent X-ray diffraction imaging.
AB  - We have developed an experimental apparatus named KOTOBUKI-1 for use in coherent
      X-ray diffraction imaging experiments of frozen-hydrated non-crystalline
      particles at cryogenic temperature. For cryogenic specimen stage with small
      positional fluctuation for a long exposure time of more than several minutes, we
      here use a cryogenic pot cooled by the evaporation cooling effect for liquid
      nitrogen. In addition, a loading device is developed to bring specimens stored in
      liquid nitrogen to the specimen stage in vacuum. The apparatus allows diffraction
      data collection for frozen-hydrated specimens at 66 K with a positional
      fluctuation of less than 0.4 MUm and provides an experimental environment to
      easily exchange specimens from liquid nitrogen storage to the specimen stage. The
      apparatus was developed and utilized in diffraction data collection of non
      crystalline particles with dimensions of MUm from material and biological
      sciences, such as metal colloid particles and chloroplast, at BL29XU of SPring-8.
      Recently, it has been applied for single-shot diffraction data collection of non
      crystalline particles with dimensions of sub-MUm using X-ray free electron laser
      at BL3 of SACLA. 

PMID- 24089836
TI  - Integrated experimental setup for angle resolved photoemission spectroscopy of
      transuranic materials.
AB  - We have developed the Angle Resolved Photoemission Spectroscopy (ARPES) system
      for transuranic materials. The ARPES transuranic system is an endstation upgrade
      to the Laser Plasma Light Source (LPLS) at Los Alamos National Laboratory. The
      LPLS is a tunable light source for photoemission with a photon energy range
      covering the vacuum ultraviolet (VUV) and soft x-ray regions (27-140 eV). The
      LPLS was designed and developed for transuranic materials. Transuranic
      photoemission is currently not permitted at the public synchrotrons worldwide in
      the VUV energy range due to sample encapsulation requirements. With the addition
      of the ARPES capability to the LPLS system there is an excellent opportunity to
      explore new details centered on the electronic structure of actinide and
      transuranic materials. 

PMID- 24089837
TI  - Observation of microscopic damage accumulation in brittle solids subjected to
      dynamic compressive loading.
AB  - Dynamic failure of brittle materials is a fundamental physical problem that has
      significantly impacts to many science and engineering disciplines. As the first
      and the most important step towards the full understanding of this problem, one
      has to observe dynamic damage accumulation in brittle solids. In this work, we
      proposed a methodology to do that and demonstrated it by studying the dynamic
      compressive damage evolution of a granitic rock loaded with a modified split
      Hopkinson pressure bar system. To ensure consistency of the experimental results,
      we used cylindrical rock samples fabricated from the same rock core and subjected
      them to identical incident loading pulse. Using a special soft recovery
      technique, we stopped the dynamic loading on the samples at different strain
      levels, ranging from 0.3% to 1.4%. Therefore, we were able to recover intact
      samples loaded all the way to the post-peak deformation stage. The recovered
      samples were subsequently examined with X-ray micro-CT scanning machine. Three
      dimensional microcrack network induced by the dynamic loading was observed and
      the evolution of microcracks as a function of the dynamic loading strain was
      obtained. 

PMID- 24089838
TI  - Rapid high-resolution spin- and angle-resolved photoemission spectroscopy with
      pulsed laser source and time-of-flight spectrometer.
AB  - A high-efficiency spin- and angle-resolved photoemission spectroscopy (spin
      ARPES) spectrometer is coupled with a laboratory-based laser for rapid high
      resolution measurements. The spectrometer combines time-of-flight (TOF) energy
      measurements with low-energy exchange scattering spin polarimetry for high
      detection efficiencies. Samples are irradiated with fourth harmonic photons
      generated from a cavity-dumped Ti:sapphire laser that provides high photon flux
      in a narrow bandwidth, with a pulse timing structure ideally matched to the needs
      of the TOF spectrometer. The overall efficiency of the combined system results in
      near-E(F) spin-resolved ARPES measurements with an unprecedented combination of
      energy resolution and acquisition speed. This allows high-resolution spin
      measurements with a large number of data points spanning multiple dimensions of
      interest (energy, momentum, photon polarization, etc.) and thus enables
      experiments not otherwise possible. The system is demonstrated with spin-resolved
      energy and momentum mapping of the L-gap Au(111) surface states, a prototypical
      Rashba system. The successful integration of the spectrometer with the pulsed
      laser system demonstrates its potential for simultaneous spin- and time-resolved
      ARPES with pump-probe based measurements.

PMID- 24089839
TI  - A versatile elevated-pressure reactor combined with an ultrahigh vacuum surface
      setup for efficient testing of model and powder catalysts under clean gas-phase
      conditions.
AB  - A small-volume reaction cell for catalytic or photocatalytic testing of solid
      materials at pressures up to 1000 Torr has been coupled to a surface-science
      setup used for standard sample preparation and characterization under ultrahigh
      vacuum (UHV). The reactor and sample holder designs allow easy sample transfer
      from/to the UHV chamber, and investigation of both planar and small amounts of
      powder catalysts under the same conditions. The sample is heated with an infrared
      laser beam and its temperature is measured with a compact pyrometer. Combined in
      a regulation loop, this system ensures fast and accurate temperature control as
      well as clean heating. The reaction products are automatically sampled and
      analyzed by mass spectrometry and/or gas chromatography (GC). Unlike previous
      systems, our GC apparatus does not use a recirculation loop and allows working in
      clean conditions at pressures as low as 1 Torr while detecting partial pressures
      smaller than 10(-4) Torr. The efficiency and versatility of the reactor are
      demonstrated in the study of two catalytic systems: butadiene hydrogenation on
      Pd(100) and CO oxidation over an AuRh/TiO2 powder catalyst.

PMID- 24089840
TI  - A miniature high repetition rate shock tube.
AB  - A miniature high repetition rate shock tube with excellent reproducibility has
      been constructed to facilitate high temperature, high pressure, gas phase
      experiments at facilities such as synchrotron light sources where space is
      limited and many experiments need to be averaged to obtain adequate signal
      levels. The shock tube is designed to generate reaction conditions of T > 600 K,
      P < 100 bars at a cycle rate of up to 4 Hz. The design of the apparatus is
      discussed in detail, and data are presented to demonstrate that well-formed shock
      waves with predictable characteristics are created, repeatably. Two synchrotron
      based experiments using this apparatus are also briefly described here,
      demonstrating the potential of the shock tube for research at synchrotron light
      sources. 

PMID- 24089841
TI  - An (ultra) high-vacuum compatible sputter source for oxide thin film growth.
AB  - A miniaturised CF-38 mountable sputter source for oxide and metal thin film
      preparation with enhanced high-vacuum and ultra-high-vacuum compatibility is
      described. The all home-built sputtering deposition device allows a high
      flexibility also in oxidic sputter materials, suitable deposition rates for
      preparation of films in the nm- and the sub-monolayer regime and excellent
      reliability and enhanced cleanliness for usage in UHV chambers. For a number of
      technologically important--yet hardly volatile--materials, the described source
      represents a significant improvement over thermal deposition techniques like
      electron-beam- or thermal evaporation, as especially the latter are no adequate
      tool to prepare atomically clean layers of refractory oxide materials.
      Furthermore, it is superior to commercially available magnetron sputter devices,
      especially for applications, where highly reproducible sub-monolayer thin film
      preparation under very clean UHV conditions is required (e.g., for studying phase
      boundary effects in catalysis). The device in turn offers the usage of a wide
      selection of evaporation materials and special target preparation procedures also
      allow the usage of pressed oxide powder targets. To prove the performance of the
      sputter-source, test preparations with technologically relevant oxide components,
      comprising ZrO2 and yttrium-stabilized ZrO2, have been carried out. A wide range
      of characterization methods (electron microscopy, X-ray photoelectron
      spectroscopy, low-energy ion scattering, atomic force microscopy, and catalytic
      testing) were applied to demonstrate the properties of the sputter-deposited thin
      film systems.

PMID- 24089842
TI  - A novel flow chamber for biodegradable alloy assessment in physiologically
      realistic environments.
AB  - In order to better understand the in vivo corrosion of biodegradable alloys, it
      is necessary to replicate the physiological environment as closely as possible.
      In this study, a novel flow chamber system is developed that allows the
      investigation of biodegradable alloy corrosion in a simulated physiological
      environment. The system is designed to reproduce flow conditions encountered in
      coronary arteries using a parallel plate setup and to allow the culturing of
      cells. Computational fluid dynamics and analytical methods are used as part of
      the design process to ensure that suitable flow conditions are maintained in the
      test region. The system is used to investigate the corrosion behavior of AZ31
      alloy foils of different thickness, in test media with and without proteins and
      in static and dynamic solutions. It is observed that pulsatile flows, similar to
      those in the coronary arteries, significantly increase corrosion rates and lead
      to a different corrosion surface morphologies relative to static immersion tests.

PMID- 24089843
TI  - The Suborbital Particle Aggregation and Collision Experiment (SPACE): studying
      the collision behavior of submillimeter-sized dust aggregates on the suborbital
      rocket flight REXUS 12.
AB  - The Suborbital Particle Aggregation and Collision Experiment (SPACE) is a novel
      approach to study the collision properties of submillimeter-sized, highly porous
      dust aggregates. The experiment was designed, built, and carried out to increase
      our knowledge about the processes dominating the first phase of planet formation.
      During this phase, the growth of planetary precursors occurs by agglomeration of
      micrometer-sized dust grains into aggregates of at least millimeters to
      centimeters in size. However, the formation of larger bodies from the so-formed
      building blocks is not yet fully understood. Recent numerical models on dust
      growth lack a particular support by experimental studies in the size range of
      submillimeters, because these particles are predicted to collide at very gentle
      relative velocities of below 1 cm/s that can only be achieved in a reduced
      gravity environment. The SPACE experiment investigates the collision behavior of
      an ensemble of silicate-dust aggregates inside several evacuated glass containers
      which are being agitated by a shaker to induce the desired collisions at chosen
      velocities. The dust aggregates are being observed by a high-speed camera,
      allowing for the determination of the collision properties of the protoplanetary
      dust analog material. The data obtained from the suborbital flight with the REXUS
      (Rocket Experiments for University Students) 12 rocket will be directly
      implemented into a state-of-the-art dust growth and collision model. 

PMID- 24089844
TI  - Portable device for magnetic stimulation: assessment survival and proliferation
      in human lymphocytes.
AB  - A device's instrumentation for magnetic stimulation on human lymphocytes is
      presented. This is a new procedure to stimulate growing cells with ferrofluid in
      vortices of magnetic field. The stimulation of magnetic vortices was provided at
      five different frequencies, from 100 to 2500 Hz and intensities from 1.13 to 4.13
      mT. To improve the stimulation effects, a paramagnetic ferrofluid was added on
      the cell culture medium. The results suggest that the frequency changes and the
      magnetic field variation produce an important increase in the number of
      proliferating cells as well as in the cellular viability. This new magnetic
      stimulation modality could trigger an intracellular mechanism to induce cell
      proliferation and cellular survival only on mitogen stimulated cells. 

PMID- 24089845
TI  - Superparamagnetic nanoparticle detection using second harmonic of magnetization
      response.
AB  - We introduce a method to improve the detection sensitivity for the magnetization
      M of superparamagnetic nanoparticles (MNP). The M response of MNP to an applied
      magnetic field H (M-H characteristics) could be divided into a linear region and
      a saturation region, which are separated at a transition point H(k). When
      applying an excitation magnetic field (H(ac)) with a frequency omega0 and an
      additional dc bias field H(dc) = H(k), the second harmonic of M reaches the
      maximum due to the nonlinearity of the M-H characteristics. It is stronger than
      any other harmonics and responsible for small H(ac) without a threshold. The
      second harmonic selected as the readout criterion for M response of MNP is
      systematically analyzed and experimentally proven.

PMID- 24089846
TI  - A compact 10 kW, 476 MHz solid state radio frequency amplifier for pre-buncher
      cavity of free electron laser injector linear accelerator.
AB  - A 10 kW, 476 MHz, 0.1% duty cycle solid state RF amplifier system for driving sub
      harmonic, pre-buncher cavity of IR-FEL injector LINAC, has been developed at
      RRCAT. The 10 kW power is achieved by combining output of eight 1400 W amplifier
      modules using 8-way planar corporate combiner. The solid state amplifier modules
      have been developed using 50 V RF LDMOS transistors which although meant for push
      pull operation are being used in single ended configuration with matching circuit
      developed on a thin (25 mils), high dielectric constant (9.7), low loss microwave
      laminate with an aim to have a compact structure. Ease of fabrication,
      modularity, small size, and low cost are the important features of this design
      which could be used as a template for low duty cycle medium to high pulsed power
      UHF amplifier system. 

PMID- 24089847
TI  - A resonant biaxial Helmholtz coil employing a fractal capacitor bank.
AB  - The design and construction of a series resonant biaxial Helmholtz coil for the
      production of magnetic fields as large as 500 G in the range of 100-2500 Hz is
      described. Important aspects of ac coil design are discussed, including:
      minimizing power losses due to the expected Joule heating, self-induced eddy
      currents, and skin resistance; controlling the stray capacitance; maximizing
      field homogeneity; and keeping peak voltages at acceptable levels. The design and
      construction of a computer-controlled, optically isolated fractal capacitor bank
      is then treated, and various aspects of capacitor selection and characterization
      were discussed. The system performance is demonstrated, including stability and
      the possibility of field component dephasing with typical magnetic samples. 

PMID- 24089848
TI  - Investigation of a compact coaxially fed switched oscillator.
AB  - To generate a relative high frequency mesoband microwave, a compact coaxially fed
      transmission line switched oscillator with high voltage capability is
      investigated. The characteristic impedance and voltage capability of the low
      impedance transmission line (LITL) have been analyzed. It is shown that the
      working voltage of the oscillator can reach up to 200 kV when it is filled by
      pressurized nitrogen and charged by a nanosecond driving source. By utilizing a
      commercial electromagnetic simulation code, the transient performance of the
      switched oscillator with a lumped resistance load is simulated. It is illustrated
      that the center frequency of the output signal reaches up to ~0.6 GHz when the
      spark gap practically closes with a single channel. Besides, the influence of the
      closing mode and rapidity of the spark gap, the permittivity of the insulator at
      the output end of the LITL, and the load impedance on the transient performance
      of the designed oscillator has been analyzed in quantification. Finally, the good
      transient performance of the switched oscillator has been preliminarily proved by
      the experiment.

PMID- 24089849
TI  - Thermal properties measurement of dry bulk materials with a cylindrical three
      layers device.
AB  - This paper presents a new method dedicated to thermal properties (conductivity
      and diffusivity) measurement of dry bulk materials including powders. The
      cylindrical three layers experimental device (brass/bulk material/stainless
      steel) and the principle of the measurement method based on a crenel thermal
      excitation are presented. The one-dimensional modeling of the system is used for
      a sensitivity analysis and to calculate the standard deviation of the estimation
      error. Experimental measurements are carried out on three bulk materials: glass
      beads, cork granules, and expanded polystyrene beads. The estimated thermal
      properties are compared with the values obtained by other measurement methods.
      Results are in good agreement with theoretical predictions: both thermal
      conductivity and diffusivity can be estimated with a good accuracy for low
      density material like cork granules or expanded polystyrene beads since only
      thermal diffusivity can be estimated for heavier materials like glass beads. It
      is finally shown that this method like all transient methods is not suited to the
      thermal characterization of wet bulk materials.

PMID- 24089850
TI  - Specific heat measurement of thin suspended SiN membrane from 8 K to 300 K using
      the 3omega-Volklein method.
AB  - We present a specific heat measurement technique adapted to thin or very thin
      suspended membranes from low temperature (8 K) to 300 K. The presented device
      allows the measurement of the heat capacity of a 70 ng silicon nitride membrane
      (50 or 100 nm thick), corresponding to a heat capacity of 1.4 * 10(-10) J/K at 8
      K and 5.1 * 10(-8) J/K at 300 K. Measurements are performed using the 3omega
      method coupled to the Volklein geometry. This configuration allows the
      measurement of both specific heat and thermal conductivity within the same
      experiment. A transducer (heater/thermometer) is used to create an oscillation of
      the heat flux on the membrane; the voltage oscillation appearing at the third
      harmonic which contains the thermal information is measured using a Wheatstone
      bridge set-up. The heat capacity measurement is performed by measuring the
      variation of the 3omega voltage over a wide frequency range and by fitting the
      experimental data using a thermal model adapted to the heat transfer across the
      membrane. The experimental data are compared to a regular Debye model; the
      specific heat exhibits features commonly seen for glasses at low temperature.

PMID- 24089851
TI  - A new in situ electrical calibration system for high temperature Calvet
      calorimeters.
AB  - A new in situ high temperature electrical calibration system was developed at
      Laboratoire National de Metrologie et d'Essais, Laboratoire Commun de Metrologie
      and integrated into a heat flux Calvet calorimeter in order to perform accurate
      and reliable measurements of enthalpy of fusion that are directly traceable to
      the International System of Units (SI). This system has been designed to enable
      the calibration of the calorimeter by electrical substitution (Joule effect) as
      well as the measurement of enthalpy of fusion in perfectly identical experimental
      conditions. The metrological features (repeatability, linearity, etc.) of the
      calorimeter have been evaluated with this system by investigating the influence
      of some parameters (level of energy, dissipation time, and temperature) on the
      determination of the sensitivity factor of its thermopiles. Two different
      procedures, for the calibration and the enthalpy measurements with this new
      electrical calibration system, have been implemented and tested by measuring the
      enthalpy of fusion of high purity 6N tin. The results obtained are in very good
      agreement with those measured by other National Metrology Institutes on the same
      material. 

PMID- 24089852
TI  - Quadrature phase interferometer for high resolution force spectroscopy.
AB  - In this article, we present a deflection measurement setup for Atomic Force
      Microscopy (AFM). It is based on a quadrature phase differential interferometer:
      we measure the optical path difference between a laser beam reflecting above the
      cantilever tip and a reference beam reflecting on the static base of the sensor.
      A design with very low environmental susceptibility and another allowing
      calibrated measurements on a wide spectral range are described. Both enable a
      very high resolution (down to 2.5*10(-15) m/?Hz), illustrated by thermal noise
      measurements on AFM cantilevers. They present an excellent long-term stability
      and a constant sensitivity independent of the optical phase of the
      interferometer. A quick review shows that our precision is equaling or out
      performing the best results reported in the literature, but for a much larger
      deflection range, up to a few MUm.

PMID- 24089853
TI  - Sandwich structure of Pd doped nanostructure TiO2 film as O2 sensor.
AB  - In this paper, we investigated the sensing properties of sandwich structure of
      TiO2/Pd/TiO2 thin films at various operating temperatures and oxygen partial
      pressures. The nanostructure TiO2 thin films were prepared by the sol-gel method.
      Various thickness of Pd buried layer was deposited by magnetron sputtering of a
      pure Pd target. The films were characterized using X-ray diffraction analysis and
      SEM. It was found that TiO2/Pd/TiO2 thin films have the p-type behavior while the
      pure TiO2 thin film is n-type semiconductor materials. We found that the
      structure of TiO2/Pd/TiO2 thin films with 10 s sputtering Pd layer has a better
      stability at 240  degrees C.

PMID- 24089854
TI  - Development of a tonometric sensor for measurement and recording of arterial
      pressure waveform.
AB  - There are many techniques and devices for measurement and recording of arterial
      blood pressure. Some of them allow (enable) additionally to observe the shape of
      a wave of arterial pressure, which can be regarded as one of the most important
      diagnostic parameters of human cardiovascular system. This paper presents a novel
      design and prototype of a new, non-invasive blood waveform measuring device. It
      expounds theoretical and experimental (including latest preliminary clinical)
      results obtained during several years of extensive investigations into blood
      pressure waveform measuring and monitoring problem. According to investigations
      performed in the laboratory and preliminary clinical evaluation, the sensor has
      linear steady-state characteristics and satisfactory dynamic properties. It is an
      efficient and accurate tool for blood pressure waveform monitoring and assessing
      the cardiovascular condition of the patients. The novelty of this solution is
      that the device is equipped with a pneumatic pressure sensor based on the
      pneumatic nozzle flapper amplifier principle with negative feedback. Due to such
      a technical solution, the device does not require any cuff, which remains an
      essential component of the majority of contemporary non-invasive blood pressure
      measurement devices; therefore, it can be used on the artery where the
      application of a cuff would be impossible (e.g., carotid artery). This advantage
      makes possible to obtain an accurate shape of blood pressure waveform with high
      fidelity, comparable to a direct measurement method. Moreover, during the
      measurement the device converts directly "pressure into pressure." Such a
      principle of operation makes possible to eliminate additional calibration (at the
      current stage of research we have eliminated the necessity of calibration in
      laboratory conditions). 

PMID- 24089855
TI  - Development of an integrated sensor module for a non-invasive respiratory
      monitoring system.
AB  - A respiratory monitoring system has been developed for analyzing the carbon
      dioxide (CO2) and oxygen (O2) concentrations in the expired air using gas
      sensors. The data can be used to estimate some medical conditions, including
      diffusion capability of the lung membrane, oxygen uptake, and carbon dioxide
      output. For this purpose, a 3-way valve derived from a servomotor was developed,
      which operates synchronously with human respiratory signals. In particular, the
      breath analysis system includes an integrated sensor module for valve control,
      data acquisition through the O2 and CO2 sensors, and respiratory rate monitoring,
      as well as software dedicated to analysis of respiratory gasses. In addition, an
      approximation technique for experimental data based on Haar-wavelet-based
      decomposition is explored to remove noise as well as to reduce the file size of
      data for long-term monitoring. 

PMID- 24089856
TI  - Fabry-Perot interferometry for long range displacement sensing.
AB  - We investigate different optical configurations of a low-finesse Fabry-Perot
      interferometer used for displacement sensing. The different configurations of the
      Fabry-Perot cavity are selected in order to achieve large measurement ranges and
      angular alignment tolerances and to make the interferometer applicable for
      targets of various reflectivity ranges. The possible working ranges and angular
      alignment tolerances are characterized with respect to the interference contrast
      which is a measure for the signal quality. The use of a confocal arrangement
      enables a measurement range of up to about 0.4 m, or to work with an angular
      tolerance of more than +/-0.2 degrees . In order to predict the optical response
      of arbitrary configurations of the Fabry-Perot interferometer, we introduce a
      simulation method based on the Airy formula and the fiber optic coupling
      efficiency.

PMID- 24089857
TI  - Fabrication of a high-aspect-ratio sub-micron tool using a cathode coated with
      stretched-out insulating layers.
AB  - This paper describes a method for preparing a high-aspect-ratio sub-micron tool
      using a cathode coated with stretched-out insulating layers and a straight
      reciprocating motion applied at the anode via the liquid membrane electrochemical
      machining (ECM). Simulation results indicate that the application of a cathode
      coated with stretched-out insulating layers is beneficial for the localization of
      ECM. Moreover, a mathematical model was derived to estimate the final average
      diameter of the fabricated tools. Experiments were conducted to verify the
      versatility and feasibility of the proposed method and its mathematical model. It
      was observed that the calculated and the experimental results are in good
      agreement with each other. A sub-micron tool with an average diameter 140.8 nm
      and an aspect ratio up to 50 was fabricated using the proposed method. 

PMID- 24089858
TI  - A reference-beam autocollimator with nanoradian sensitivity from mHz to kHz and
      dynamic range of 10(7).
AB  - We describe an autocollimating optical angle sensor with a dynamic range of 9
      mrad and nrad/?Hz sensitivity at frequencies from 5 mHz to 3 kHz. This work
      improves the standard multi-slit autocollimator design by adding two optical
      components, a reference mirror and a condensing lens. This autocollimator makes a
      differential measurement between a reference mirror and a target mirror,
      suppressing common-mode noise sources. The condensing lens reduces optical
      aberrations, increases intensity, and improves image quality. To further improve
      the stability of the device at low frequencies the body of the autocollimator is
      designed to reduce temperature variations and their effects. A new data
      processing technique was developed in order to suppress the effects of
      imperfections in the CCD.

PMID- 24089859
TI  - Development of a novel sort of exponent-sine-shaped flexure hinges.
AB  - Various types of flexure hinges have been developed to construct flexural
      mechanisms, however, all these hinges may have limited moving accuracies,
      blocking performance improvements of the flexural mechanisms. In this paper, a
      novel sort of exponent-sine-shaped flexure hinges (ESSFHs) with asymmetric
      structures is proposed to achieve much higher motion accuracy. To characterize
      elastic deformation behavior of the ESSFHs, a novel finite beam based matrix
      modeling (FBMM) method is employed to calculate the compliance matrix and the
      defined non-dimensional precision factors without executing laborious integration
      operations. Furthermore, finite element analysis is conducted and compared with
      the FBMM method, the maximum deviation of the obtained compliances and the
      precision factors by the two methods is less than 8%, well demonstrating the
      efficiency of the analytical method. Comparisons of the accuracies of the ESSFHs
      and certain state-of-the-art flexure hinges verify that the proposed ESSFHs can
      not only significantly improve the motion accuracy but also decrease the inherent
      parasitic motions of conventional flexure hinges. Based on the established
      analytical models, influences of the dimensional parameters on the compliances
      and the motion accuracy of the ESSFHs are well revealed. Finally, performances of
      the ESSFH and the efficiency of the analytical model are well investigated by
      means of experimental tests. 

PMID- 24089860
TI  - Carbon nanotube coated fiber Bragg grating for photomechanical optic modulator.
AB  - We have demonstrated novel concept of utilizing the photomechanical actuation in
      carbon nanotubes (CNTs) to tune and reversibly switch the Bragg wavelength. When
      fiber Bragg grating coated with CNTs (CNT-FBG) is exposed externally to a wide
      range of optical wavelengths, e.g., ultraviolet to infrared (0.2-200 MUm), a
      strain is induced in the CNTs which alters the grating pitch and refractive index
      in the CNT-FBG system resulting in a shift in the Bragg wavelength. This novel
      approach will find applications in telecommunication, sensors and actuators, and
      also for real time monitoring of the photomechanical actuation in nanoscale
      materials. 

PMID- 24089861
TI  - One kilometer (1 km) electric solar wind sail tether produced automatically.
AB  - We produced a 1 km continuous piece of multifilament electric solar wind sail
      tether of MUm-diameter aluminum wires using a custom made automatic tether
      factory. The tether comprising 90,704 bonds between 25 and 50 MUm diameter wires
      is reeled onto a metal reel. The total mass of 1 km tether is 10 g. We reached a
      production rate of 70 m/24 h and a quality level of 10/00 loose bonds and 20/00
      rebonded ones. We thus demonstrated that production of long electric solar wind
      sail tethers is possible and practical.

PMID- 24089862
TI  - Design and characterization of a nano-Newton resolution thrust stand.
AB  - The paper describes the design, calibration, and characterization of a thrust
      stand capable of nano-Newton resolution. A low uncertainty calibration method is
      proposed and demonstrated. A passive eddy current based damper, which is non
      contact and vacuum compatible, is employed. Signal analysis techniques are used
      to perform noise characterization, and potential sources are identified.
      Calibrated system noise floor suggests thrust measurement resolution of the order
      of 10 nN is feasible under laboratory conditions. Force measurement from this
      balance for a standard macroscale dielectric barrier discharge (DBD) plasma
      actuator is benchmarked with a commercial precision balance of 9.8 MUN resolution
      and is found to be in good agreement. Published results of a microscale DBD
      plasma actuator force measurement and low pressure characterization of
      conventional plasma actuators are presented for completeness. 

PMID- 24089863
TI  - An energy-filtering device coupled to a quadrupole mass spectrometer for soft
      landing molecular ions on surfaces with controlled energy.
AB  - We have developed an energy-filtering device coupled to a quadrupole mass
      spectrometer to deposit ionized molecules on surfaces with controlled energy in
      ultra high vacuum environment. Extensive numerical simulations as well as direct
      measurements show that the ion beam flying out of a quadrupole exhibits a high
      energy tail decreasing slowly up to several hundred eV. This energy distribution
      renders impossible any direct soft-landing deposition of molecular ions. To
      remove this high-energy tail by energy filtering, a 127 degrees  electrostatic
      sector and a specific triplet lenses were designed and added after the last
      quadrupole of a triple quadrupole mass spectrometer. The results obtained with
      this energy-filtering device show clearly the elimination of the high-energy
      tail. The ion beam that impinges on the sample surface satisfies now the soft
      landing criterion for molecular ions, opening new research opportunities in the
      numerous scientific domains involving charges adsorbed on insulating surfaces. 

PMID- 24089864
TI  - The effect of specimen surface curvature on x-ray diffraction peak profiles.
AB  - The effect of specimen surface curvature on profiles of asymmetric X-ray
      diffraction peaks obtained using the Bragg-Brentano geometry with a position
      sensitive detector (PSD) was studied. Asymmetric diffraction peaks were
      experimentally obtained from cylindrical surfaces with controlled curvature.
      Peaks were collected for a set of curvature radii, diffraction angles, and
      materials. A mathematical approach and a computer model for calculations of peak
      profiles were developed: a general method for computation of peak profiles is
      consideration of diffraction cones intersection with the PSD surface. Effects of
      axial and radial divergence, finite sample size, and local surface tilt were
      included in the model. Calculated peak profiles agree with reflections obtained
      experimentally at a wide range of curvature radii and diffraction angle values.
      Computation of important characteristics such as the peak centroid and change in
      position of the maximum and full-width-half-maximum is provided. 

PMID- 24089865
TI  - Vacuum chamber-free centrifuge with magnetic bearings.
AB  - Centrifuges are devices that separate particles of different densities and sizes
      through the application of a centrifugal force. If a centrifuge could be operated
      under atmospheric conditions, all vacuum-related components such as the vacuum
      chamber, vacuum pump, diffusion pump, and sealing could be removed from a
      conventional centrifuge system. The design and manufacturing procedure for
      centrifuges could then be greatly simplified to facilitate the production of
      lightweight centrifuge systems of smaller volume. Furthermore, the maintenance
      costs incurred owing to wear and tear due to conventional ball bearings would be
      eliminated. In this study, we describe a novel vacuum chamber-free centrifuge
      supported by magnetic bearings. We demonstrate the feasibility of the vacuum
      chamber-free centrifuge by presenting experimental results that verify its high
      speed support capability and motoring power capacity. 

PMID- 24089866
TI  - A hyperspectral imaging system for an accurate prediction of the above-ground
      biomass of individual rice plants.
AB  - Biomass is an important component of the plant phenomics, and the existing
      methods for biomass estimation for individual plants are either destructive or
      lack accuracy. In this study, a hyperspectral imaging system was developed for
      the accurate prediction of the above-ground biomass of individual rice plants in
      the visible and near-infrared spectral region. First, the structure of the system
      and the influence of various parameters on the camera acquisition speed were
      established. Then the system was used to image 152 rice plants, which selected
      from the rice mini-core collection, in two stages, the tillering to elongation (T
      E) stage and the booting to heading (B-H) stage. Several variables were extracted
      from the images. Following, linear stepwise regression analysis and 5-fold cross
      validation were used to select effective variables for model construction and
      test the stability of the model, respectively. For the T-E stage, the R(2) value
      was 0.940 for the fresh weight (FW) and 0.935 for the dry weight (DW). For the B
      H stage, the R(2) value was 0.891 for the FW and 0.783 for the DW. Moreover,
      estimations of the biomass using visible light images were also calculated. These
      comparisons showed that hyperspectral imaging performed better than the visible
      light imaging. Therefore, this study provides not only a stable hyperspectral
      imaging platform but also an accurate and nondestructive method for the
      prediction of biomass for individual rice plants. 

PMID- 24089867
TI  - Twin sample chamber for simultaneous comparative transport measurements in a
      diamond anvil cell.
AB  - In static high pressure experiments, performed within a diamond anvil cell (DAC),
      several different methods of thermometry may be employed to determine the
      temperature of the sample. Due to different DAC designs or particular
      experimental designs or goals, uncertainties in the determination of the
      temperature of a given sample exist. To overcome the inaccuracy in comparing the
      temperature dependence of transport properties of different materials at high
      pressure, we have used a novel design of resistivity measurement in a twin sample
      chamber built on an insulated gasket in a DAC. In this design, the transport
      properties of two samples will be measured simultaneously and therefore the two
      samples will always be in the same relative temperatures. The uncertainties in
      the temperatures of the two samples will be exactly the same and therefore their
      relative phase diagram will be compared precisely. The pressures of the chambers
      can be slightly different and is easily determined by the ruby pieces placed in
      each chamber. To demonstrate the feasibility of this method we have compared the
      superconducting properties of two YBa2Cu3O(7-x) (0 <= x <= 0.65) samples with
      slightly different superconducting transition temperatures at ambient pressure as
      a function of pressures up to 11 GPa. The upper limit of the pressure achieved
      using this design would be lower than single chamber gaskets. The highest
      achievable pressure, as in a conventional single hole setup, depends upon the
      thickness of the gasket, the culet size, the size, and symmetry of the sample
      chamber. For the twin chamber, it also depends upon the separation of the holes
      from each other as well as from the edge of the culet.

PMID- 24089868
TI  - Design and implementation of a novel portable atomic layer deposition/chemical
      vapor deposition hybrid reactor.
AB  - We report the development of a novel portable atomic layer deposition chemical
      vapor deposition (ALD/CVD) hybrid reactor setup. Unique feature of this reactor
      is the use of ALD/CVD mode in a single portable deposition system to fabricate
      multi-layer thin films over a broad range from "bulk-like" multi-micrometer to
      nanometer atomic dimensions. The precursor delivery system and control
      architecture are designed so that continuous reactant flows for CVD and cyclic
      pulsating flows for ALD mode are facilitated. A custom-written LabVIEW program
      controls the valve sequencing to allow synthesis of different kinds of film
      structures under either ALD or CVD mode or both. The entire reactor setup weighs
      less than 40 lb and has a relatively small footprint of 8 * 9 in., making it
      compact and easy for transportation. The reactor is tested in the ALD mode with
      titanium oxide (TiO2) ALD using tetrakis(diethylamino)titanium and water vapor.
      The resulting growth rate of 0.04 nm/cycle and purity of the films are in good
      agreement with literature values. The ALD/CVD hybrid mode is demonstrated with
      ALD of TiO2 and CVD of tin oxide (SnOx). Transmission electron microscopy images
      of the resulting films confirm the formation of successive distinct TiO2-ALD and
      SnO(x)-CVD layers.

PMID- 24089869
TI  - A 4 K cryogenic probe for use in magnetic resonance force microscopy experiments.
AB  - The detailed design of a mechanically detected nuclear magnetic resonance probe
      using the SPAM (Springiness Preservation by Aligning Magnetization) geometry,
      operating at 4 K, in vacuum, and a several-Tesla magnetic field is described. The
      probe head is vibration-isolated well enough from the environment by a three
      spring suspension system that the cantilever achieves thermal equilibrium with
      the environment without the aid of eddy current damping. The probe uses an ultra
      soft Si cantilever with a Ni sphere attached to its tip, and magnetic resonance
      is registered as a change in the resonant frequency of the driven cantilever. The
      RF system uses frequency sweeps for adiabatic rapid passage using a 500 MUm
      diameter RF coil wound around a sapphire rod. The RF coil and optical fiber of
      the interferometer used to sense the cantilever's position are both located with
      respect to the cantilever using a Garbini micropositioner, and the sample stage
      is mounted on an Attocube nanopositioner. 

PMID- 24089870
TI  - An extreme ultraviolet Michelson interferometer for experiments at free-electron
      lasers.
AB  - We present a Michelson interferometer for 13.5 nm soft x-ray radiation. It is
      characterized in a proof-of-principle experiment using synchrotron radiation,
      where the temporal coherence is measured to be 13 fs. The curvature of the thin
      film beam splitter membrane is derived from the observed fringe pattern. The
      applicability of this Michelson interferometer at intense free-electron lasers is
      investigated, particularly with respect to radiation damage. This study
      highlights the potential role of such Michelson interferometers in solid density
      plasma investigations using, for instance, extreme soft x-ray free-electron
      lasers. A setup using the Michelson interferometer for pseudo-Nomarski
      interferometry is proposed. 

PMID- 24089871
TI  - Easily implementable field programmable gate array-based adaptive optics system
      with state-space multichannel control.
AB  - In this paper, an easily implementable adaptive optics system (AOS) based on a
      real-time field programmable gate array (FPGA) platform with state-space
      multichannel control programmed by LabVIEW has been developed, and also
      integrated into a laser focusing system successfully. To meet the requirements of
      simple programming configuration and easy integration with other devices, the
      FPGA-based AOS introduces a standard operation procedure including AOS
      identification, computation, and operation. The overall system with a 32-channel
      driving signal for a deformable mirror (DM) as input and a Zernike polynomial via
      a lab-made Shack-Hartmann wavefront sensor (SHWS) as output is optimally
      identified to construct a multichannel state-space model off-line. In real-time
      operation, the FPGA platform first calculates the Zernike polynomial of the
      optical wavefront measured from the SHWS as the feedback signal. Then, a state
      space multichannel controller according to the feedback signal and the identified
      model is designed and implemented in the FPGA to drive the DM for phase
      distortion compensation. The current FPGA-based AOS is capable of suppressing low
      frequency thermal disturbances with a steady-state phase error of less than 0.1
      pi within less than 10 time steps when the control loop is operated at a
      frequency of 30 Hz. 

PMID- 24089872
TI  - An accelerated exposure and testing apparatus for building joint sealants.
AB  - The design, fabrication, and implementation of a computer-controlled exposure and
      testing apparatus for building joint sealants are described in this paper. This
      apparatus is unique in its ability to independently control and monitor
      temperature, relative humidity, ultraviolet (UV) radiation, and mechanical
      deformation. Each of these environmental factors can be controlled precisely over
      a wide range of conditions during periods of a month or more. Moreover, as
      controlled mechanical deformations can be generated, in situ mechanical
      characterization tests can be performed without removing specimens from the
      chamber. Temperature and humidity were controlled during our experiments via a
      precision temperature regulator and proportional mixing of dry and moisture
      saturated air; while highly uniform UV radiation was attained by attaching the
      chamber to an integrating sphere-based radiation source. A computer-controlled
      stepper motor and a transmission system were used to provide precise movement
      control. The reliability and effectiveness of the apparatus were demonstrated on
      a model sealant material. The results clearly show that this apparatus provides
      an excellent platform to study the long-term durability of building joint
      sealants. 

PMID- 24089873
TI  - High-temperature experiments using a resistively heated high-pressure membrane
      diamond anvil cell.
AB  - We describe a reliable high performance resistive heating method developed for
      the membrane diamond anvil cell. This method generates homogenous high
      temperatures at high pressure in the whole sample for extended operation period.
      It relies on two mini coil heaters made of Pt-Rh alloy wire mounted around the
      diamond anvils and gasket, while temperature is monitored by two K-type
      thermocouples mounted near the sample. The sample, diamonds, and tungsten-carbide
      seats are thermally insulated from the piston and cylinder keeping the cell
      temperature below 750 K while the sample temperature is 1200 K. The cell with the
      heaters is placed in a vacuum oven to prevent oxidation and unnecessary heat
      loss. This assembly allows complete remote operation, ideally suited for
      experiments at synchrotron facilities. Capabilities of the setup are demonstrated
      for in situ Raman and synchrotron x-ray diffraction measurements. We show
      experimental measurements from isothermal compression at 900 K and 580 K to 100
      GPa and 185 GPa, respectively, and quasi-isobaric compression at 95 GPa over 1000
      K. 

PMID- 24089874
TI  - An innovative experimental setup for the measurement of sputtering yield induced
      by keV energy ions.
AB  - An innovative experimental equipment allowing to study the sputtering induced by
      ion beam irradiation is presented. The sputtered particles are collected on a
      catcher which is analyzed in situ by Auger electron spectroscopy without breaking
      the ultra high vacuum (less than 10(-9) mbar), avoiding thus any problem linked
      to possible contamination. This method allows to measure the angular distribution
      of sputtering yield. It is now possible to study the sputtering of many elements
      such as carbon based materials. Preliminary results are presented in the case of
      highly oriented pyrolytic graphite and tungsten irradiated by an Ar(+) beam at
      2.8 keV and 7 keV, respectively. 

PMID- 24089875
TI  - Very low field magnetic resonance imaging with spintronic sensors.
AB  - A very low field magnetic resonance imaging (MRI) setup based on magnetoresistive
      superconducting mixed sensors is presented. A flux transformer is used to achieve
      coupling between the sample to image and the mixed sensor. The novel detector was
      implemented in a spin echo MRI experiment, exposing the mixed sensor to RF pulses
      without use of any RF switch. The performance of the novel detector is given in
      terms of signal-to-noise ratio and is compared with classical tuned coils. 

PMID- 24089876
TI  - Note: Pneumatically actuated and kinematically positioned optical mounts
      compatible with laser-cooling experiments.
AB  - We present two complementary designs of pneumatically actuated and kinematically
      positioned optics mounts: one designed for vertical mounting and translation, the
      other designed for horizontal mounting and translation. The design and measured
      stability make these mounts well-suited to experiments with laser-cooled atoms. 

PMID- 24089877
TI  - Note: Determination of torsional spring constant of atomic force microscopy
      cantilevers: combining normal spring constant and classical beam theory.
AB  - A technique has been developed for the calculation of torsional spring constants
      for AFM cantilevers based on the combination of the normal spring constant and
      plate/beam theory. It is easy to apply and allow the determination of torsional
      constants for stiff cantilevers where the thermal power spectrum is difficult to
      obtain due to the high resonance frequency and low signal/noise ratio. The
      applicability is shown to be general and this simple approach can thus be used to
      obtain torsional constants for any beam shaped cantilever.

PMID- 24089878
TI  - Note: A new angle-resolved proton energy spectrometer.
AB  - In typical laser-driven proton acceleration experiments Thomson parabola proton
      spectrometers are used to measure the proton spectra with very small acceptance
      angle in specific directions. Stacks composed of CR-39 nuclear track detectors,
      imaging plates, or radiochromic films are used to measure the angular
      distributions of the proton beams, respectively. In this paper, a new proton
      spectrometer, which can measure the spectra and angular distributions
      simultaneously, has been designed. Proton acceleration experiments performed on
      the Xtreme light III laser system demonstrates that the spectrometer can give
      angle-resolved spectra with a large acceptance angle. This will be conductive to
      revealing the acceleration mechanisms, optimization, and applications of laser
      driven proton beams. 

PMID- 24089879
TI  - Note: Arbitrary periodical mechanical vibrations can be realized in the resonant
      state based on multiple tuning fork structure.
AB  - We develop a novel approach to match harmonics and vibration modes based on the
      mechanism of multiple tuning fork structure (MTFS), through which it is promising
      to realize arbitrary periodical vibrations in the resonant state. A prototype
      three-layer MTFS with first three harmonics is presented to verify the
      feasibility of the proposed principle. The matching process and experimental
      results confirm the unique advantages of MTFS, as discussed in the theoretical
      analysis. Typical periodical motions, including sawtooth, square, half-wave
      rectified, and full-wave rectified waveforms, are achieved by the syntheses of
      resonant harmonics. 

PMID- 24089880
TI  - Note: A novel rotary actuator driven by only one piezoelectric actuator.
AB  - This paper presents a novel piezo-driven rotary actuator based on the parasitic
      motion principle. Output performances of the rotary actuator were tested and
      discussed. Experiment results indicate that using only one piezoelectric actuator
      and simple sawtooth wave control, the rotary actuator reaches the rotation
      velocity of about 20,097 MUrad/s when the driving voltage is 100 V and the
      driving frequency is 90 Hz. The actuator can rotate stably with the minimum
      resolution of 0.7 MUrad. This paper verifies feasibility of the parasitic motion
      principle for applications of rotary actuators, providing new design ideas for
      precision piezoelectric rotary actuators.

PMID- 24089881
TI  - Note: Vignetting calibration and temperature correction for casting billets.
AB  - A method for calibration of vignetting coefficient is proposed in this paper to
      solve the distortion of temperature measurement using a CCD-based pyrometer. On
      this basis, a hybrid temperature measurement system, which comprises of an array
      CCD camera with high resolution and a single spot colorimetric thermometer, is
      introduced to eliminate the influences of surface striped iron oxide scale, dust,
      and emissivity on temperature measurement for casting billets. Currently, the
      system has been successfully applied and verified in some continuous casting
      production lines. The vignetting estimation error of 0.052 and the maximum
      temperature measurement fluctuation of 5  degrees C were achieved in these
      measurements. 

PMID- 24089882
TI  - Note: A self-calibrating electrometer for atmospheric charge measurements from a
      balloon platform.
AB  - Charged aerosol particles and water droplets are abundant throughout the lower
      atmosphere, and may influence interactions between small cloud droplets. This
      note describes a small, disposable sensor for the measurement of charge in non
      thunderstorm cloud, which is an improvement of an earlier sensor [K. A. Nicoll
      and R. G. Harrison, Rev. Sci. Instrum. 80, 014501 (2009)]. The sensor utilizes a
      self-calibrating current measurement method. It is designed for use on a free
      balloon platform alongside a standard meteorological radiosonde, measuring
      currents from 2 fA to 15 pA and is stable to within 5 fA over a temperature range
      of 5  degrees C to -60  degrees C. During a balloon flight with the charge sensor
      through a stratocumulus cloud, charge layers up to 40 pC m(-3) were detected on
      the cloud edges.

PMID- 24089883
TI  - Note: An object detection method for active camera.
AB  - To solve the problems caused by a changing background during object detection in
      active camera, this paper proposes a new method based on SURF (speeded up robust
      features) and data clustering. The SURF feature points of each image are
      extracted, and each cluster center is calculated by processing the data
      clustering of k adjacent frames. Templates for each class are obtained by
      calculating the histograms within the regions around the center points of the
      clustering classes. The window of the moving object can be located by finding the
      region that satisfies the histogram matching result between adjacent frames.
      Experimental results demonstrate that the proposed method can improve the
      effectiveness of object detection. 

PMID- 24089884
TI  - Note: Automated electrochemical etching and polishing of silver scanning
      tunneling microscope tips.
AB  - Fabrication of sharp and smooth Ag tips is crucial in optical scanning probe
      microscope experiments. To ensure reproducible tip profiles, the polishing
      process is fully automated using a closed-loop laminar flow system to deliver the
      electrolytic solution to moving electrodes mounted on a motorized translational
      stage. The repetitive translational motion is controlled precisely on the MUm
      scale with a stepper motor and screw-thread mechanism. The automated setup allows
      reproducible control over the tip profile and improves smoothness and sharpness
      of tips (radius 27 +/- 18 nm), as measured by ultrafast field emission. 

PMID- 24089885
TI  - Note: Comparative experimental studies on the performance of 2-2 piezocomposite
      for medical ultrasound transducers.
AB  - The paper reports the experimental investigation of the behavior of 2-2 Lead
      Zirconate Titanate (PZT)-polymer composite transducers array for clinical
      ultrasound equipments. Several 2-2 plate composites having the same dicing pitch
      of 0.11 mm and different volume fractions were manufactured and investigated.
      Measurements were performed through different techniques such as electrical
      impedance, pulse-echo, and Laser Doppler Vibrometer. With the last one, maps of
      the surface displacement were presented relative to thickness mode and first
      lateral mode resonance frequencies. The transducers with volume fractions of the
      40% resulted markedly inefficient, whereas the largest bandwidth and best band
      shape were achieved by the 50%. 

PMID- 24089887
TI  - Point/Counterpoint. Increasing dependence on industry-funded research creates
      higher risk of biased reporting in medical physics.

PMID- 24089888
TI  - Revisit of combined parallel-beam/cone-beam or fan-beam/cone-beam imaging.
AB  - PURPOSE: This aim of this paper is to revisit the parallel-beam/cone-beam or fan
      beam/cone-beam imaging configuration, and to investigate whether this
      configuration has any advantages. METHODS: Twenty years ago, it was suggested to
      simultaneously use a parallel-beam (or a fan-beam) collimator and a cone-beam
      collimator to acquire single photon emission computed tomography data. The
      motivation was that the parallel-beam (or the fan-beam) collimator can provide
      sufficient sampling, while the cone-beam collimator is able to provide higher
      photon counts. Even with higher total counts, this hybrid system does not give
      significant improvement (if any) in terms of image noise and artifacts reduction.
      If a conventional iterative maximum-likelihood expectation-maximization algorithm
      is used to reconstruct the image, the resultant reconstruction may be worse than
      the parallel-beam-only (or fan-beam-only) system. This paper uses the singular
      value decomposition (SVD) analysis to explain this phenomenon. RESULTS: The SVD
      results indicate that the parallel-beam-only and the fan-beam-only system
      outperform the combined systems. CONCLUSIONS: The optimal imaging system does not
      necessary to be the one that generates the projections with highest signal-to
      noise ratio and best resolution.

PMID- 24089890
TI  - An introduction to molecular imaging in radiation oncology: a report by the AAPM
      Working Group on Molecular Imaging in Radiation Oncology (WGMIR).
AB  - Molecular imaging is the direct or indirect noninvasive monitoring and recording
      of the spatial and temporal distribution of in vivo molecular, genetic, and/or
      cellular processes for biochemical, biological, diagnostic, or therapeutic
      applications. Molecular images that indicate the presence of malignancy can be
      acquired using optical, ultrasonic, radiologic, radionuclide, and magnetic
      resonance techniques. For the radiation oncology physicist in particular, these
      methods and their roles in molecular imaging of oncologic processes are reviewed
      with respect to their physical bases and imaging characteristics, including
      signal intensity, spatial scale, and spatial resolution. Relevant molecular
      terminology is defined as an educational assist. Current and future clinical
      applications in oncologic diagnosis and treatment are discussed. National
      initiatives for the development of basic science and clinical molecular imaging
      techniques and expertise are reviewed, illustrating research opportunities in as
      well as the importance of this growing field.

PMID- 24089889
TI  - Vision 20/20: Single photon counting x-ray detectors in medical imaging.
AB  - Photon counting detectors (PCDs) with energy discrimination capabilities have
      been developed for medical x-ray computed tomography (CT) and x-ray (XR) imaging.
      Using detection mechanisms that are completely different from the current energy
      integrating detectors and measuring the material information of the object to be
      imaged, these PCDs have the potential not only to improve the current CT and XR
      images, such as dose reduction, but also to open revolutionary novel applications
      such as molecular CT and XR imaging. The performance of PCDs is not flawless,
      however, and it seems extremely challenging to develop PCDs with close to ideal
      characteristics. In this paper, the authors offer our vision for the future of
      PCD-CT and PCD-XR with the review of the current status and the prediction of (1)
      detector technologies, (2) imaging technologies, (3) system technologies, and (4)
      potential clinical benefits with PCDs. 

PMID- 24089891
TI  - Performance of 12 DIR algorithms in low-contrast regions for mass and density
      conserving deformation.
AB  - PURPOSE: Deformable image registration (DIR) has become a key tool for adaptive
      radiotherapy to account for inter- and intrafraction organ deformation. Of
      contemporary interest, the application to deformable dose accumulation requires
      accurate deformation even in low contrast regions where dose gradients may exist
      within near-uniform tissues. One expects high-contrast features to generally be
      deformed more accurately by DIR algorithms. The authors systematically assess the
      accuracy of 12 DIR algorithms and quantitatively examine, in particular, low
      contrast regions, where accuracy has not previously been established. METHODS:
      This work investigates DIR algorithms in three dimensions using deformable gel
      (DEFGEL) [U. J. Yeo, M. L. Taylor, L. Dunn, R. L. Smith, T. Kron, and R. D.
      Franich, "A novel methodology for 3D deformable dosimetry," Med. Phys. 39, 2203
      2213 (2012)], for application to mass- and density-conserving deformations. CT
      images of DEFGEL phantoms with 16 fiducial markers (FMs) implanted were acquired
      in deformed and undeformed states for three different representative deformation
      geometries. Nonrigid image registration was performed using 12 common algorithms
      in the public domain. The optimum parameter setup was identified for each
      algorithm and each was tested for deformation accuracy in three scenarios: (I)
      original images of the DEFGEL with 16 FMs; (II) images with eight of the FMs
      mathematically erased; and (III) images with all FMs mathematically erased. The
      deformation vector fields obtained for scenarios II and III were then applied to
      the original images containing all 16 FMs. The locations of the FMs estimated by
      the algorithms were compared to actual locations determined by CT imaging. The
      accuracy of the algorithms was assessed by evaluation of three-dimensional
      vectors between true marker locations and predicted marker locations. RESULTS:
      The mean magnitude of 16 error vectors per sample ranged from 0.3 to 3.7, 1.0 to
      6.3, and 1.3 to 7.5 mm across algorithms for scenarios I to III, respectively.
      The greatest accuracy was exhibited by the original Horn and Schunck optical flow
      algorithm. In this case, for scenario III (erased FMs not contributing to driving
      the DIR calculation), the mean error was half that of the modified demons
      algorithm (which exhibited the greatest error), across all deformations. Some
      algorithms failed to reproduce the geometry at all, while others accurately
      deformed high contrast features but not low-contrast regions-indicating poor
      interpolation between landmarks. CONCLUSIONS: The accuracy of DIR algorithms was
      quantitatively evaluated using a tissue equivalent, mass, and density conserving
      DEFGEL phantom. For the model studied, optical flow algorithms performed better
      than demons algorithms, with the original Horn and Schunck performing best. The
      degree of error is influenced more by the magnitude of displacement than the
      geometric complexity of the deformation. As might be expected, deformation is
      estimated less accurately for low-contrast regions than for high-contrast
      features, and the method presented here allows quantitative analysis of the
      differences. The evaluation of registration accuracy through observation of the
      same high contrast features that drive the DIR calculation is shown to be
      circular and hence misleading.

PMID- 24089892
TI  - Cancer risk estimates from radiation therapy for heterotopic ossification
      prophylaxis after total hip arthroplasty.
AB  - PURPOSE: Heterotopic ossification (HO) is a frequent complication following total
      hip arthroplasty. This study was conducted to calculate the radiation dose to
      organs-at-risk and estimate the probability of cancer induction from radiotherapy
      for HO prophylaxis. METHODS: Hip irradiation for HO with a 6 MV photon beam was
      simulated with the aid of a Monte Carlo model. A realistic humanoid phantom
      representing an average adult patient was implemented in Monte Carlo environment
      for dosimetric calculations. The average out-of-field radiation dose to stomach,
      liver, lung, prostate, bladder, thyroid, breast, uterus, and ovary was
      calculated. The organ-equivalent-dose to colon, that was partly included within
      the treatment field, was also determined. Organ dose calculations were carried
      out using three different field sizes. The dependence of organ doses upon the
      block insertion into primary beam for shielding colon and prosthesis was
      investigated. The lifetime attributable risk for cancer development was estimated
      using organ, age, and gender-specific risk coefficients. RESULTS: For a typical
      target dose of 7 Gy, organ doses varied from 1.0 to 741.1 mGy by the field
      dimensions and organ location relative to the field edge. Blocked field
      irradiations resulted in a dose range of 1.4-146.3 mGy. The most probable
      detriment from open field treatment of male patients was colon cancer with a high
      risk of 564.3 * 10(-5) to 837.4 * 10(-5) depending upon the organ dose magnitude
      and the patient's age. The corresponding colon cancer risk for female patients
      was (372.2-541.0) * 10(-5). The probability of bladder cancer development was
      more than 113.7 * 10(-5) and 110.3 * 10(-5) for males and females, respectively.
      The cancer risk range to other individual organs was reduced to (0.003-68.5) *
      10(-5). CONCLUSIONS: The risk for cancer induction from radiation therapy for HO
      prophylaxis after total hip arthroplasty varies considerably by the treatment
      parameters, organ site in respect to treatment volume and patient's gender and
      age. The presented risk estimates may be useful in the follow-up studies of
      irradiated patients.

PMID- 24089893
TI  - 3D tomodosimetry using long scintillating fibers: a feasibility study.
AB  - PURPOSE: 3D dosimetry is recognized as an ideal for patient-specific quality
      assurance (QA) of highly conformal radiotherapy treatments. However, existing 3D
      dosimeters are not straightforward to implement in the clinic, as their read-out
      procedure is often tedious and their accuracy, precision, and/or sample size
      exhibit limitations. The purpose of this work is to develop a 3D dosimeter based
      on the concept of tomodosimetry inside concentric cylindrical planes using long
      scintillating fibers for the QA of modern radiotherapy techniques such as
      intensity-modulated radiation therapy (IMRT) or intensity-modulated arc therapy
      (IMAT). METHODS: Using a model-based simulation, scintillating fibers were
      modeled on three concentric cylindrical planes of radii 2.5, 5.0, and 7.5 cm,
      inside a 10 cm radius water-equivalent cylinder phantom. The phantom was set to
      rotate around its central axis, made parallel to the linac gantry axis of
      rotation. Light acquisitions were simulated using the calculated dose from the
      treatment planning software and reconstructed in each cylindrical plane at a
      resolution of 1 mm(2) using a total-variation minimization iterative
      reconstruction algorithm. The 3D dose was then interpolated from the
      reconstructed cylindrical plane doses at a resolution of 1 mm(3). Different
      scintillating fiber patterns were compared by varying the angle of each fiber in
      its cylindrical plane and introducing a light-tight cut in each fiber. The
      precision of the reconstructed cylindrical dose distribution was evaluated using
      a Poisson modeling of the acquired light signals and the accuracy of the
      interpolated 3D dose was evaluated using an IMRT clinical plan for a prostate
      case. RESULTS: Straight scintillating fiber patterns with light-tight cuts were
      the most accurate in cylindrical dose reconstruction, showing less than 0.5 mm
      distance-to-agreement in dose gradients and a mean local dose difference of less
      than 0.2% in the high dose region for a 10 * 10 cm(2) field. The precision
      attained with this fiber configuration was less than 0.9% in the high dose, low
      gradient region of an IMRT segment for light acquisitions of 0.1 MU over a 360
      degree rotation of the cylinder phantom. 3D dose interpolation for the IMRT
      clinical plan yielded an overall dose difference with the reference input of less
      than 1%, except in high dose gradients. CONCLUSIONS: Using long scintillating
      fibers inside rotating, concentric cylindrical planes, the authors demonstrate
      that their tomodosimetry method has the potential for high resolution, precise,
      and accurate 3D dosimetry. Moreover, because of its water-equivalence and
      rotational symmetry, this design should find interesting application for both
      treatment QA and machine commissioning.

PMID- 24089894
TI  - A further investigation of the centroid-to-centroid method for stereotactic lung
      radiotherapy: a phantom study.
AB  - PURPOSE: Our previous study [B. Lu et al., "A patient alignment solution for lung
      SBRT setups based on a deformable registration technique," Med. Phys. 39(12),
      7379-7389 (2012)] proposed a deformable-registration-based patient setup strategy
      called the centroid-to-centroid (CTC) method, which can perform an accurate
      alignment of internal-target-volume (ITV) centroids between averaged four
      dimensional computed tomography and cone-beam computed tomography (CBCT) images.
      Scenarios with variations between CBCT and simulation CT caused by irregular
      breathing and/or tumor change were not specifically considered in the patient
      study [B. Lu et al., "A patient alignment solution for lung SBRT setups based on
      a deformable registration technique," Med. Phys. 39(12), 7379-7389 (2012)] due to
      the lack of both a sufficiently large patient data sample and a method of tumor
      tracking. The aim of this study is to thoroughly investigate and compare the
      impacts of breathing pattern and tumor change on both the CTC and the translation
      only (T-only) gray-value mode strategies by employing a four-dimensional (4D)
      lung phantom. METHODS: A sophisticated anthropomorphic 4D phantom (CIRS Dynamic
      Thorax Phantom model 008) was employed to simulate all desired respiratory
      variations. The variation scenarios were classified into four groups: inspiration
      to expiration ratio (IE ratio) change, tumor trajectory change, tumor position
      change, tumor size change, and the combination of these changes. For each
      category the authors designed several scenarios to demonstrate the effects of
      different levels of breathing variation on both of the T-only and the CTC
      methods. Each scenario utilized 4DCT and CBCT scans. The ITV centroid alignment
      discrepancies for CTC and T-only were evaluated. The dose-volume-histograms
      (DVHs) of ITVs for two extreme cases were analyzed. RESULTS: Except for some
      extreme cases in the combined group, the accuracy of the CTC registration was
      about 2 mm for all cases for both the single and the combined scenarios. The
      performance of the CTC method was insensitive to region-of-registration (ROR)
      size selections, as suggested by the comparable accuracy between 1 and 2 cm
      expansions of the ROR selections for the method. The T-only method was suitable
      for some single scenarios, such as trajectory variation, position variation, and
      size variation. However, for combined scenarios and/or a large variation in the
      IE ratio, the T-only method failed to produce reasonable registration results
      (within 3 mm). The discrepancy was close to, or even greater than, 1 cm. In
      addition, unlike the CTC method, the T-only method was sensitive to the ROR size
      selection. The DVH analysis suggested that a large ITV to PTV margin should be
      considered if a breathing pattern variation is observed. CONCLUSIONS: The phantom
      study demonstrated that the CTC method was reliable for scenarios in which
      breathing pattern variation was involved. The T-only gray value method worked for
      some scenarios, but not for scenarios that involved an IE ratio variation. For
      scenarios involving position variation, the T-only method worked only with a
      careful selection of the ROR, whereas the CTC method was independent of ROR size
      as long as the ITVs were included in the ROR. One indication of the dose
      consequence analysis was that a large ITV to PTV margin should be considered if a
      breathing pattern variation is observed.

PMID- 24089895
TI  - Calculation of dose distributions for 12 106Ru/106Rh ophthalmic applicator models
      with the PENELOPE Monte Carlo code.
AB  - PURPOSE: For decades, (106)Ru/(106)Rh ophthalmic applicators have been widely
      used to treat intraocular malignancies with good clinical outcomes. Determining
      the dosimetry of such applicators is challenging because of their spherical
      shape, the low range of emitted betas and the steep gradients involved.
      Furthermore, there is a lack of dose distribution data in the literature for some
      applicator models. It is crucial to understand the generated dose distributions
      to improve the treatment planning process. This study aims to calculate the dose
      distributions in water for 12 commercially available (106)Ru/(106)Rh ophthalmic
      applicators. METHODS: The applicators were modeled using the Monte Carlo (MC)
      code PENELOPE-2008.1. A planar nonclinical applicator was also simulated. Depth
      dose profiles along the central axis and lateral dose profiles at several depths
      were calculated and compared with the available published measured and calculated
      data. In the absence of published data, measurements performed by the
      manufacturer were used. RESULTS: For some applicators, the calculated results
      obtained in this work showed improved consistency with the available experimental
      data compared with previously published calculations. For others, the data
      calculated in this work represent the first published dose data. CONCLUSIONS: The
      MC code PENELOPE-2008.1 can accurately calculate the dose distributions for
      (106)Ru/(106)Rh ophthalmic applicators. The obtained set of tabulated dose
      distribution values may be useful for quality assurance of treatment planning
      systems and as a reference for comparison with future measurements and
      calculations.

PMID- 24089896
TI  - Dosimetric evaluation of photon dose calculation under jaw and MLC shielding.
AB  - PURPOSE: The accuracy of photon dose calculation algorithms in out-of-field
      regions is often neglected, despite its importance for organs at risk and
      peripheral dose evaluation. The present work has assessed this for the
      anisotropic analytical algorithm (AAA) and the Acuros-XB algorithms implemented
      in the Eclipse treatment planning system. Specifically, the regions shielded by
      the jaw, or the MLC, or both MLC and jaw for flattened and unflattened beams have
      been studied. METHODS: The accuracy in out-of-field dose under different
      conditions was studied for two different algorithms. Measured depth doses out of
      the field, for different field sizes and various distances from the beam edge
      were compared with the corresponding AAA and Acuros-XB calculations in water.
      Four volumetric modulated arc therapy plans (in the RapidArc form) were optimized
      in a water equivalent phantom, PTW Octavius, to obtain a region always shielded
      by the MLC (or MLC and jaw) during the delivery. Doses to different points
      located in the shielded region and in a target-like structure were measured with
      an ion chamber, and results were compared with the AAA and Acuros-XB
      calculations. Photon beams of 6 and 10 MV, flattened and unflattened were used
      for the tests. RESULTS: Good agreement between calculated and measured depth
      doses was found using both algorithms for all points measured at depth greater
      than 3 cm. The mean dose differences (+/- 1SD) were -8% +/- 16%, -3% +/- 15%, 
      16% +/- 18%, and -9% +/- 16% for measurements vs AAA calculations and -10% +/-
      14%, -5% +/- 12%, -19% +/- 17%, and -13% +/- 14% for Acuros-XB, for 6X, 6
      flattening-filter free (FFF), 10X, and 10FFF beams, respectively. The same
      figures for dose differences relative to the open beam central axis dose were: 
      0.1% +/- 0.3%, 0.0% +/- 0.4%, -0.3% +/- 0.3%, and -0.1% +/- 0.3% for AAA and 
      0.2% +/- 0.4%, -0.1% +/- 0.4%, -0.5% +/- 0.5%, and -0.3% +/- 0.4% for Acuros-XB.
      Buildup dose was overestimated with AAA, while Acuros-XB gave results more
      consistent with measurements. From RapidArc plan analysis the average difference
      between calculation and measurement in the shielded region was -0.3% +/- 0.4% and
      -2.5% +/- 1.2% for AAA and Acuros-XB, respectively, relative to the mean target
      dose value (1.6% +/- 2.3%, -12.7% +/- 4.0% if relative to each local value).
      These values were compared with the corresponding differences in the target
      structure: -0.7% +/- 2.3% for AAA, and -0.5% +/- 2.3% for Acuros-XB. CONCLUSIONS:
      The two algorithms analyzed showed encouraging results in predicting out-of-field
      region dose for clinical use.

PMID- 24089897
TI  - Predicting pathologic tumor response to chemoradiotherapy with histogram
      distances characterizing longitudinal changes in 18F-FDG uptake patterns.
AB  - PURPOSE: A family of fluorine-18 ((18)F)-fluorodeoxyglucose ((18)F-FDG) positron
      emission tomography (PET) features based on histogram distances is proposed for
      predicting pathologic tumor response to neoadjuvant chemoradiotherapy (CRT).
      These features describe the longitudinal change of FDG uptake distribution within
      a tumor. METHODS: Twenty patients with esophageal cancer treated with CRT plus
      surgery were included in this study. All patients underwent PET/CT scans before
      (pre-) and after (post-) CRT. The two scans were first rigidly registered, and
      the original tumor sites were then manually delineated on the pre-PET/CT by an
      experienced nuclear medicine physician. Two histograms representing the FDG
      uptake distribution were extracted from the pre- and the registered post-PET
      images, respectively, both within the delineated tumor. Distances between the two
      histograms quantify longitudinal changes in FDG uptake distribution resulting
      from CRT, and thus are potential predictors of tumor response. A total of 19
      histogram distances were examined and compared to both traditional PET response
      measures and Haralick texture features. Receiver operating characteristic
      analyses and Mann-Whitney U test were performed to assess their predictive
      ability. RESULTS: Among all tested histogram distances, seven bin-to-bin and
      seven crossbin distances outperformed traditional PET response measures using
      maximum standardized uptake value (AUC = 0.70) or total lesion glycolysis (AUC =
      0.80). The seven bin-to-bin distances were: L(2) distance (AUC = 0.84), chi(2)
      distance (AUC = 0.83), intersection distance (AUC = 0.82), cosine distance (AUC =
      0.83), squared Euclidean distance (AUC = 0.83), L(1) distance (AUC = 0.82), and
      Jeffrey distance (AUC = 0.82). The seven crossbin distances were: quadratic-chi
      distance (AUC = 0.89), earth mover distance (AUC = 0.86), fast earth mover
      distance (AUC = 0.86), diffusion distance (AUC = 0.88), Kolmogorov-Smirnov
      distance (AUC = 0.88), quadratic form distance (AUC = 0.87), and match distance
      (AUC = 0.84). These crossbin histogram distance features showed slightly higher
      prediction accuracy than texture features on post-PET images. CONCLUSIONS: The
      results suggest that longitudinal patterns in (18)F-FDG uptake characterized
      using histogram distances provide useful information for predicting the
      pathologic response of esophageal cancer to CRT.

PMID- 24089898
TI  - Use of dMLC for implementation of dynamic respiratory-gated radiation therapy.
AB  - PURPOSE: To simulate and evaluate the use of dynamic multileaf collimators (dMLC)
      in respiratory gating to compensate for baseline drift. METHODS: Tumor motion
      tracking data from 30 lung tumors over 322 treatment fractions was analyzed with
      the finite state model. A dynamic respiratory gating window was established in
      real-time by determining the average positions during the previous two end-of
      expiration breathing phases and centering the dMLC aperture on a weighted average
      of these positions. A simulated dMLC with physical motion constraints was used in
      dynamic gating treatment simulations. Fluence maps were created to provide a
      statistical description of radiation delivery for each fraction. Duty cycle was
      also calculated for each fraction. RESULTS: The average duty cycle was 2.3%
      greater under dynamic gating conditions. Dynamic gating also showed higher
      fluences and less tumor obstruction. Additionally, dynamic gating required fewer
      beam toggles and each delivery period was longer on average than with static
      gating. CONCLUSIONS: The use of dynamic gating showed better performance than
      static gating and the physical constraints of a dMLC were shown to not be an
      impediment to dynamic gating.

PMID- 24089899
TI  - Two-dimensional inverse planning and delivery with a preclinical image guided
      microirradiator.
AB  - PURPOSE: Recent advances in preclinical radiotherapy systems have provided the
      foundation for scaling many of the elements of clinical radiation therapy
      practice to the dimensions and energy demanded in small animal studies. Such
      systems support the technical capabilities to accurately deliver highly complex
      dose distributions, but methods to optimize and deliver such distributions remain
      in their infancy. This study developed an optimization method based on
      empirically measured two-dimensional dose kernel measurements to deliver
      arbitrary planar dose distributions on a recently developed small animal
      radiotherapy platform. METHODS: A two-dimensional dose kernel was measured with
      repeated radiochromic film measurements for the circular 1 mm diameter fixed
      collimator of the small animal radiotherapy system at 1 cm depth in a solid water
      phantom. This kernel was utilized in a sequential quadratic programming
      optimization framework to determine optimal beam positions and weights to deliver
      an arbitrary desired dose distribution. The positions and weights were then
      translated to a set of stage motions to automatically deliver the optimized dose
      distribution. End-to-end efficacy of the framework was quantified through five
      repeated deliveries of two dosimetric challenges: (1) a 5 mm radius bullseye
      distribution, and (2) a "sock" distribution contained within a 9 * 13 mm bounding
      box incorporating rectangular, semicircular, and exponentially decaying geometric
      constructs and a rectangular linear dose gradient region. These two challenges
      were designed to gauge targeting, geometric, and dosimetric fidelity. RESULTS:
      Optimization of the bullseye and sock distributions required 2.1 and 5.9 min and
      utilized 50 and 77 individual beams for delivery, respectively. Automated
      delivery of the resulting optimized distributions, validated using radiochromic
      film measurements, revealed an average targeting accuracy of 0.32 mm, and a
      dosimetric delivery error along four line profiles taken through the sock
      distribution of 3.9%. Mean absolute delivery error across the 0-1 Gy linear dose
      gradient over 7.5 mm was 0.01 Gy. CONCLUSIONS: The work presented here
      demonstrates the potential for complex dose distributions to be planned and
      automatically delivered with millimeter scale heterogeneity at submillimeter
      accuracy. This capability establishes the technical foundation for preclinical
      validation of biologically guided radiotherapy investigations and development of
      unique radiobiological experiments.

PMID- 24089900
TI  - An optimization algorithm for 3D real-time lung tumor tracking during arc therapy
      using kV projection images.
AB  - PURPOSE: To develop a real-time markerless 3D tumor tracking using kilovoltage
      (kV) cone-beam CT (CBCT) projection images during volumetric modulated arc
      therapy (VMAT) treatment of lung tumors. METHODS: The authors have developed a
      method to identify the position of lung tumors during VMAT treatment, where the
      current mean 3D position is detected and subsequently the real time 3D position
      is obtained. The mean position is evaluated by iteratively minimizing an
      observation error function between the tumor coordinate detected in the imaging
      plane and the coordinate of the corresponding projection of the estimated mean
      position. The 3D trajectory is reconstructed using the same optimization
      formalism, where an observation error function is minimized for tumor positions
      confined within a predefined amplitude bin as determined from the superior
      inferior tumor motion. Dynamic phantom experiments were performed and image data
      acquired during patient treatment were analyzed to characterize the
      reconstruction ability of the proposed method. RESULTS: The proposed algorithm
      needs to acquire kV projection data until a certain gantry angle is passed
      through, termed the black-out angle, before accurate estimation mean 3D tumor
      position is possible. The black-out angle for the mean position method is
      approximately 20 degrees , while for the 3D trajectory reconstruction an
      additional ~ 15 degrees  is required. The mean 3D position and 3D trajectory
      reconstruction are accurate within +/- 0.5 mm. CONCLUSIONS: The authors present a
      real-time tracking framework to locate lung tumors during VMAT treatment using an
      optimization algorithm applied to CBCT kV projection images taken concomitantly
      with the treatment delivery. The authors' technique does not introduce
      significant additional dose and can be used for real-time treatment monitoring.

PMID- 24089901
TI  - Validation of mathematical models for the prediction of organs-at-risk dosimetric
      metrics in high-dose-rate gynecologic interstitial brachytherapy.
AB  - PURPOSE: Given the complicated nature of an interstitial gynecologic
      brachytherapy treatment plan, the use of a quantitative tool to evaluate the
      quality of the achieved metrics compared to clinical practice would be
      advantageous. For this purpose, predictive mathematical models to predict the
      D2cc of rectum and bladder in interstitial gynecologic brachytherapy are
      discussed and validated. METHODS: Previous plans were used to establish the
      relationship between D2cc and the overlapping volume of the organ at risk with
      the targeted area (C0) or a 1-cm expansion of the target area (C1). Three
      mathematical models were evaluated: D2cc = alpha*C1 + beta (LIN); D2cc = alpha -
      exp(-beta*C0) (EXP); and a mixed approach (MIX), where both C0 and C1 were inputs
      of the model. The parameters of the models were optimized on a training set of
      patient data, and the predictive error of each model (predicted D2cc - real D2cc)
      was calculated on a validation set of patient data. The data of 20 patients were
      used to perform a K-fold cross validation analysis, with K = 2, 4, 6, 8, 10, and
      20. RESULTS: MIX was associated with the smallest mean prediction error <6.4% for
      an 18-patient training set; LIN had an error <8.5%; EXP had an error <8.3%. Best
      case scenario analysis shows that an error <= 5% can be achieved for a ten
      patient training set with MIX, an error <= 7.4% for LIN, and an error <= 6.9% for
      EXP. The error decreases with the increase in training set size, with the most
      marked decrease observed for MIX. CONCLUSIONS: The MIX model can predict the D2cc
      of the organs at risk with an error lower than 5% with a training set of ten
      patients or greater. The model can be used in the development of quality
      assurance tools to identify treatment plans with suboptimal sparing of the organs
      at risk. It can also be used to improve preplanning and in the development of
      real-time intraoperative planning tools.

PMID- 24089902
TI  - A novel method for routine quality assurance of volumetric-modulated arc therapy.
AB  - PURPOSE: Volumetric-modulated arc therapy (VMAT) is delivered through
      synchronized variation of gantry angle, dose rate, and multileaf collimator (MLC)
      leaf positions. The delivery dynamic nature challenges the parameter setting
      accuracy of linac control system. The purpose of this study was to develop a
      novel method for routine quality assurance (QA) of VMAT linacs. METHODS: ArcCheck
      is a detector array with diodes distributing in spiral pattern on cylindrical
      surface. Utilizing its features, a QA plan was designed to strictly test all
      varying parameters during VMAT delivery on an Elekta Synergy linac. In this plan,
      there are 24 control points. The gantry rotates clockwise from 181 degrees  to
      179 degrees . The dose rate, gantry speed, and MLC positions cover their ranges
      commonly used in clinic. The two borders of MLC-shaped field seat over two
      columns of diodes of ArcCheck when the gantry rotates to the angle specified by
      each control point. The ratio of dose rate between each of these diodes and the
      diode closest to the field center is a certain value and sensitive to the MLC
      positioning error of the leaf crossing the diode. Consequently, the positioning
      error can be determined by the ratio with the help of a relationship curve. The
      time when the gantry reaches the angle specified by each control point can be
      acquired from the virtual inclinometer that is a feature of ArcCheck. The gantry
      speed between two consecutive control points is then calculated. The
      aforementioned dose rate is calculated from an acm file that is generated during
      ArcCheck measurements. This file stores the data measured by each detector in 50
      ms updates with each update in a separate row. A computer program was written in
      MATLAB language to process the data. The program output included MLC positioning
      errors and the dose rate at each control point as well as the gantry speed
      between control points. To evaluate this method, this plan was delivered for four
      consecutive weeks. The actual dose rate and gantry speed were compared with the
      QA plan specified. Additionally, leaf positioning errors were intentionally
      introduced to investigate the sensitivity of this method. RESULTS: The
      relationship curves were established for detecting MLC positioning errors during
      VMAT delivery. For four consecutive weeks measured, 98.4%, 94.9%, 89.2%, and
      91.0% of the leaf positioning errors were within +/- 0.5 mm, respectively. For
      the intentionally introduced leaf positioning systematic errors of -0.5 and +1
      mm, the detected leaf positioning errors of 20 Y1 leaf were -0.48 +/- 0.14 and
      1.02 +/- 0.26 mm, respectively. The actual gantry speed and dose rate closely
      followed the values specified in the VMAT QA plan. CONCLUSIONS: This method can
      assess the accuracy of MLC positions and the dose rate at each control point as
      well as the gantry speed between control points at the same time. It is efficient
      and suitable for routine quality assurance of VMAT.

PMID- 24089903
TI  - Characterization of a constrained paired-view technique in iterative
      reconstruction for breast tomosynthesis.
AB  - PURPOSE: The order in which the projection views are employed in the
      reconstruction of tomosynthesis by iterative algorithms, such as simultaneous
      algebraic reconstruction technique and maximum likelihood, has a strong effect on
      the rate of convergence, accuracy, and the edge-blurring artifacts in the
      reconstructed image. The purpose of this investigation was to characterize and
      evaluate the effects of ordering schemes on image quality for breast
      tomosynthesis reconstruction and to explore a new constrained paired-view
      technique that could provide reduction of reconstruction artifacts. In this work,
      the authors compared several different ordering schemes and characterized the
      image quality and the formation of out-of-plane artifacts. Furthermore, a new
      normalization method is presented. It produces more accurate reconstructions with
      reduced artifacts comparing to the standard method of sequential ordering.
      METHODS: In addition to visual assessment of image quality, several indices such
      as the signal-difference-to-noise ratio, the artifact-spread function, and the
      lesion detectability (d(')) were computed to quantitatively evaluate the effect
      of ordering scheme. The sets of breast tomosynthesis projection images were
      simulated for reconstruction; one set had uniform background (white noise only)
      and the other two contained both anatomic background and quantum noise. Clinical
      breast images were also studied for comparison. RESULTS: The authors have
      quantified the image quality in reconstructed slices for a range of tumor sizes.
      The authors' proposed method provides better performance for all of the metrics
      tested (contrast, d('), and the level of artifacts) both for the uniform phantom
      case and in the presence of anatomical structure. CONCLUSIONS: The paired
      projection normalization provides better performance in the image quality of the
      reconstructed slices, and results in a lower level of artifacts in the Z
      direction. This implies that even a relatively simple method like the "side-to
      side" sequence, which pairs two symmetrical projections with equal angular
      distance from the central projection, would achieve better reconstructed image
      quality than the conventional "step-by-step" method, which uses sequential
      projections one after another.

PMID- 24089904
TI  - Characterization of a clinical unit for digital radiography based on irradiation
      side sampling technology.
AB  - PURPOSE: A characterization of a clinical unit for digital radiography (FUJIFILM
      FDR D-EVO) is presented. This system is based on the irradiation side sampling
      (ISS) technology and can be equipped with two different scintillators: one
      traditional gadolinium-oxysulphide phosphor (GOS) and a needle structured cesium
      iodide (CsI) phosphor panel. METHODS: The characterization was achieved in terms
      of response curve, modulation transfer function (MTF), noise power spectra (NPS),
      detective quantum efficiency (DQE), and psychophysical parameters (contrast
      detail analysis with an automatic reading of CDRAD images). For both
      scintillation screens the authors accomplished the measurements with four
      standard beam conditions: RAQ3, RQA5, RQA7, and RQA9. RESULTS: At the Nyquist
      frequency (3.33 lp/mm) the MTF is about 35% and 25% for CsI and GOS detectors,
      respectively. The CsI scintillator has better noise properties than the GOS
      screen in almost all the conditions. This is particularly true for low-energy
      beams, where the noise for the GOS system can go up to a factor 2 greater than
      that found for CsI. The DQE of the CsI detector reaches a peak of 60%, 60%, 58%,
      and 50% for the RQA3, RQA5, RQA7, and RQA9 beams, respectively, whereas for the
      GOS screen the maximum DQE is 40%, 44%, 44%, and 35%. The contrast-detail
      analysis confirms that in the majority of cases the CsI scintillator is able to
      provide improved outcomes to those obtained with the GOS screen. CONCLUSIONS: The
      limited diffusion of light produced by the ISS reading makes possible the
      achievement of very good spatial resolution. In fact, the MTF of the unit with
      the CsI panel is only slightly lower to that achieved with direct conversion
      detectors. The combination of very good spatial resolution, together with the
      good noise properties reached with the CsI screen, allows achieving DQE on
      average about 1.5 times greater than that obtained with GOS. In fact, the DQE of
      unit equipped with CsI is comparable to the best alternative methods available
      which are based on the same technology, and similar to others based on an a-Se
      direct conversion detectors.

PMID- 24089905
TI  - Template-based CTA to x-ray angio rigid registration of coronary arteries in
      frequency domain with automatic x-ray segmentation.
AB  - PURPOSE: A key challenge for image guided coronary interventions is accurate and
      absolutely robust image registration bringing together preinterventional
      information extracted from a three-dimensional (3D) patient scan and live
      interventional image information. In this paper, the authors present a novel
      scheme for 3D to two-dimensional (2D) rigid registration of coronary arteries
      extracted from preoperative image scan (3D) and a single segmented intraoperative
      x-ray angio frame in frequency and spatial domains for real-time angiography
      interventions by C-arm fluoroscopy. METHODS: Most existing rigid registration
      approaches require a close initialization due to the abundance of local minima
      and high complexity of search algorithms. The authors' method eliminates this
      requirement by transforming the projections into translation-invariant Fourier
      domain for estimating the 3D pose. For 3D rotation recovery, template Digitally
      Reconstructed Radiographs (DRR) as candidate poses of 3D vessels of segmented
      computed tomography angiography are produced by rotating the camera (image
      intensifier) around the DICOM angle values with a specific range as in C-arm
      setup. The authors have compared the 3D poses of template DRRs with the segmented
      x-ray after equalizing the scales in three domains, namely, Fourier magnitude,
      Fourier phase, and Fourier polar. The best rotation pose candidate was chosen by
      one of the highest similarity measures returned by the methods in these domains.
      It has been noted in literature that frequency domain methods are robust against
      noise and occlusion which was also validated by the authors' results. 3D
      translation of the volume was then recovered by distance-map based BFGS
      optimization well suited to convex structure of the authors' objective function
      without local minima due to distance maps. A novel automatic x-ray vessel
      segmentation was also performed in this study. RESULTS: Final results were
      evaluated in 2D projection space for patient data; and with ground truth values
      and landmark distances for the images acquired with a solid phantom vessel.
      Results validate that rotation recovery in frequency domain is robust against
      differences in segmentations in two modalities. Distance-map translation is
      successful in aligning coronary trees with highest possible overlap. CONCLUSIONS:
      Numerical and qualitative results show that single view rigid alignment in
      projection space is successful. This work can be extended with multiple views to
      resolve depth ambiguity and with deformable registration to account for nonrigid
      motion in patient data.

PMID- 24089906
TI  - Nonlocal denoising using anisotropic structure tensor for 3D MRI.
AB  - PURPOSE: Noise in magnetic resonance imaging (MRI) data is widely recognized to
      be harmful to image processing and subsequent quantitative analysis. To
      ameliorate the effects of image noise, the authors present a structure-tensor
      based nonlocal mean (NLM) denoising technique that can effectively reduce noise
      in MRI data and improve tissue characterization. METHODS: The proposed 3D NLM
      algorithm uses a structure tensor to characterize information around tissue
      boundaries. The similarity weight of a pixel (or patch), which determines its
      contribution to the denoising process, is determined by the intensity and
      structure tensor simultaneously. Meanwhile, similarity of structure tensors is
      computed using an affine-invariant Riemannian metrics, which compares tensor
      properties more comprehensively and avoids orientation inaccuracy of structure
      subsequently. The proposed method is further extended for denoising high
      dimensional MRI data such as diffusion weighted MRI. It is also extended to
      handle Rician noise corruption so that denoising effects are further enhanced.
      RESULTS: The proposed method was implemented in both simulated datasets and
      multiply modalities of real 3D MRI datasets. Comparisons with related state-of
      the-art algorithms demonstrated that this method improves denoising performance
      qualitatively and quantitatively. CONCLUSIONS: In this paper, high order
      structure information of 3D MRI was characterized by 3D structure tensor and
      compared for NLM denoising in a Riemannian space. Experiments with simulated and
      real human MRI data demonstrate a great potential of the proposed technique for
      routine clinical use.

PMID- 24089907
TI  - Power spectrum analysis of the x-ray scatter signal in mammography and breast
      tomosynthesis projections.
AB  - PURPOSE: To analyze the frequency domain characteristics of the signal in
      mammography images and breast tomosynthesis projections with patient tissue
      texture due to detected scattered x-rays. METHODS: Acquisitions of x-ray
      projection images of 19 different patient breasts were simulated using previously
      acquired volumetric patient images. Acquisition of these images was performed
      with a dedicated breast CT prototype system, and the images were classified into
      voxels representing skin, adipose, and glandular tissue with a previously
      validated automated algorithm. The classified three dimensional images then
      underwent simulated mechanical compression representing that which is performed
      during acquisition of mammography and breast tomosynthesis images. The
      acquisition of projection images of each patient breast was simulated using Monte
      Carlo methods with each simulation resulting in two images: one of the primary
      (non-scattered) signal and one of the scatter signal. To analyze the scatter
      signal for both mammography and breast tomosynthesis, two projections images of
      each patient breast were simulated, one with the x-ray source positioned at 0
      degrees  (mammography and central tomosynthesis projection) and at 30 degrees 
      (wide tomosynthesis projection). The noise power spectra (NPS) for both the
      scatter signal alone and the total signal (primary + scatter) for all images were
      obtained and the combined results of all patients analyzed. The total NPS was fit
      to the expected power-law relationship NPS(f) = k/f beta and the results were
      compared with those previously published on the power spectrum characteristics of
      mammographic texture. The scatter signal alone was analyzed qualitatively and a
      power-law fit was also performed. RESULTS: The mammography and tomosynthesis
      projections of three patient breasts were too small to analyze, so a total of 16
      patient breasts were analyzed. The values of beta for the total signal of the 0
      degrees  projections agreed well with previously published results. As expected,
      the scatter power spectrum reflected a fast drop-off with increasing spatial
      frequency, with a reduction of four orders of magnitude by 0.1 lp/mm. The beta
      values for the scatter signal were 6.14 and 6.39 for the 0 degrees  and 30
      degrees  projections, respectively. CONCLUSIONS: Although the low-frequency
      characteristics of scatter in mammography and breast tomosynthesis were known, a
      quantitative analysis of the frequency domain characteristics of this signal was
      needed in order to optimize previously proposed software-based x-ray scatter
      reduction algorithms for these imaging modalities.

PMID- 24089908
TI  - Predicting diagnostic error in radiology via eye-tracking and image analytics:
      preliminary investigation in mammography.
AB  - PURPOSE: The primary aim of the present study was to test the feasibility of
      predicting diagnostic errors in mammography by merging radiologists' gaze
      behavior and image characteristics. A secondary aim was to investigate group
      based and personalized predictive models for radiologists of variable experience
      levels. METHODS: The study was performed for the clinical task of assessing the
      likelihood of malignancy of mammographic masses. Eye-tracking data and diagnostic
      decisions for 40 cases were acquired from four Radiology residents and two breast
      imaging experts as part of an IRB-approved pilot study. Gaze behavior features
      were extracted from the eye-tracking data. Computer-generated and BIRADS images
      features were extracted from the images. Finally, machine learning algorithms
      were used to merge gaze and image features for predicting human error. Feature
      selection was thoroughly explored to determine the relative contribution of the
      various features. Group-based and personalized user modeling was also
      investigated. RESULTS: Machine learning can be used to predict diagnostic error
      by merging gaze behavior characteristics from the radiologist and textural
      characteristics from the image under review. Leveraging data collected from
      multiple readers produced a reasonable group model [area under the ROC curve
      (AUC) = 0.792 +/- 0.030]. Personalized user modeling was far more accurate for
      the more experienced readers (AUC = 0.837 +/- 0.029) than for the less
      experienced ones (AUC = 0.667 +/- 0.099). The best performing group-based and
      personalized predictive models involved combinations of both gaze and image
      features. CONCLUSIONS: Diagnostic errors in mammography can be predicted to a
      good extent by leveraging the radiologists' gaze behavior and image content.

PMID- 24089910
TI  - Investigating the feasibility of photon-counting K-edge imaging at high x-ray
      fluxes using nonlinearity corrections.
AB  - PURPOSE: Pulse pileup occurring at high x-ray fluxes can severely degrade the
      energy resolution provided by a photon counting detector, which can represent a
      problem in spectroscopic CT when performing quantitative material discrimination
      tasks. As the effects of pileup can be most easily seen as a degradation of a
      detector's count rate linearity at high fluxes, it has been proposed previously
      to quantify and correct these nonlinearities. While this strategy has been
      applied successfully to materials without K-edges, it is currently unknown if
      this still prevails when using medical contrast agents. The purpose of this study
      is to close this gap. METHODS: A Medipix2MXR Hexa detector was employed,
      featuring a pixel pitch of 165 [micro sign]m and a 1 mm thick CdTe sensor. A
      phantom containing various concentrations of iodine and gadolinium contrast
      agents was subject to energy selective CT acquisitions, using a pulsable x-ray
      source operated at 70 kVp. These acquisitions were obtained at low and high
      photon fluxes of 1.0 * 10(6) and 1.3 * 10(7) mm(-2) s(-1), respectively.
      Nonlinearity corrections were applied to the high-flux projections and for each
      pixel separately. The results were compared to the results at low photon fluxes.
      RESULTS: At high fluxes, a general reduction of the reconstructed attenuation
      coefficients was observed, which could be partially recovered using the
      correction strategy applied. The spectroscopic separation of iodine from the
      phantom material, however, degraded with increasing x-ray flux. In contrast to
      this, gadolinium could still be discriminated almost as well as in the low flux
      case. CONCLUSIONS: Nonlinearity corrections applied to high flux measurements can
      help to recover attenuation coefficients normally obtained at low fluxes for low
      Z materials, which do not exhibit an absorption edge in the relevant energy
      range. However, as a result of a significant change of the x-ray spectrum, the
      spectroscopic contrast normally observed for iodine was found to vanish with
      increasing x-ray flux. In other words, the authors' results indicate that
      nonlinearity corrections may be feasible only when the K-edge of interest is
      sufficiently high compared to the mean photon energy, and that spectroscopic CT
      at high x-ray fluxes may suffer from less limitations when using high-Z materials
      as contrast agents. A future study should aim to confirm these findings under
      clinical conditions.

PMID- 24089909
TI  - 4D CT lung ventilation images are affected by the 4D CT sorting method.
AB  - PURPOSE: Four-dimensional (4D) computed tomography (CT) ventilation imaging is a
      novel promising technique for lung functional imaging. The current standard 4D CT
      technique using phase-based sorting frequently results in artifacts, which may
      deteriorate the accuracy of ventilation imaging. The purpose of this study was to
      quantify the variability of 4D CT ventilation imaging due to 4D CT sorting.
      METHODS: 4D CT image sets from nine lung cancer patients were each sorted by the
      phase-based method and anatomic similarity-based method, designed to reduce
      artifacts, with corresponding ventilation images created for each method.
      Artifacts in the resulting 4D CT images were quantified with the artifact score
      which was defined based on the difference between the normalized cross
      correlation for CT slices within a CT data segment and that for CT slices
      bordering the interface between adjacent CT data segments. The ventilation
      variation was quantified using voxel-based Spearman rank correlation coefficients
      for all lung voxels, and Dice similarity coefficients (DSC) for the spatial
      overlap of low-functional lung volumes. Furthermore, the correlations with
      matching single-photon emission CT (SPECT) ventilation images (assumed ground
      truth) were evaluated for three patients to investigate which sorting method
      provides higher physiologic accuracy. RESULTS: Anatomic similarity-based sorting
      reduced 4D CT artifacts compared to phase-based sorting (artifact score, 0.45 +/-
      0.14 vs 0.58 +/- 0.24, p = 0.10 at peak-exhale; 0.63 +/- 0.19 vs 0.71 +/- 0.31, p
      = 0.25 at peak-inhale). The voxel-based correlation between the two ventilation
      images was 0.69 +/- 0.26 on average, ranging from 0.03 to 0.85. The DSC was 0.71
      +/- 0.13 on average. Anatomic similarity-based sorting yielded significantly
      fewer lung voxels with paradoxical negative ventilation values than phase-based
      sorting (5.0 +/- 2.6% vs 9.7 +/- 8.4%, p = 0.05), and improved the correlation
      with SPECT ventilation regionally. CONCLUSIONS: The variability of 4D CT
      ventilation imaging due to 4D CT sorting was moderate overall and substantial in
      some cases, suggesting that 4D CT artifacts are an important source of variations
      in 4D CT ventilation imaging. Reduction of 4D CT artifacts provided more
      physiologically convincing and accurate ventilation estimates. Further studies
      are needed to confirm this result.

PMID- 24089911
TI  - Low dose tomographic fluoroscopy: 4D intervention guidance with running prior.
AB  - PURPOSE: Today's standard imaging technique in interventional radiology is the
      single- or biplane x-ray fluoroscopy which delivers 2D projection images as a
      function of time (2D+T). This state-of-the-art technology, however, suffers from
      its projective nature and is limited by the superposition of the patient's
      anatomy. Temporally resolved tomographic volumes (3D+T) would significantly
      improve the visualization of complex structures. A continuous tomographic data
      acquisition, if carried out with today's technology, would yield an excessive
      patient dose. Recently the authors proposed a method that enables tomographic
      fluoroscopy at the same dose level as projective fluoroscopy which means that if
      scanning time of an intervention guided by projective fluoroscopy is the same as
      that of an intervention guided by tomographic fluoroscopy, almost the same dose
      is administered to the patient. The purpose of this work is to extend authors'
      previous work and allow for patient motion during the intervention. METHODS: The
      authors propose the running prior technique for adaptation of a prior image. This
      adaptation is realized by a combination of registration and projection
      replacement. In a first step the prior is deformed to the current position via
      affine and deformable registration. Then the information from outdated
      projections is replaced by newly acquired projections using forward and
      backprojection steps. The thus adapted volume is the running prior. The proposed
      method is validated by simulated as well as measured data. To investigate motion
      during intervention a moving head phantom was simulated. Real in vivo data of a
      pig are acquired by a prototype CT system consisting of a flat detector and a
      continuously rotating clinical gantry. RESULTS: With the running prior technique
      it is possible to correct for motion without additional dose. For an application
      in intervention guidance both steps of the running prior technique, registration
      and replacement, are necessary. Reconstructed volumes based on the running prior
      show high image quality without introducing new artifacts and the interventional
      materials are displayed at the correct position. CONCLUSIONS: The running prior
      improves the robustness of low dose 3D+T intervention guidance toward intended or
      unintended patient motion.

PMID- 24089912
TI  - Evaluation of the robustness of the preprocessing technique improving reversible
      compressibility of CT images: tested on various CT examinations.
AB  - PURPOSE: To modify the preprocessing technique, which was previously proposed,
      improving compressibility of computed tomography (CT) images to cover the
      diversity of three dimensional configurations of different body parts and to
      evaluate the robustness of the technique in terms of segmentation correctness and
      increase in reversible compression ratio (CR) for various CT examinations.
      METHODS: This study had institutional review board approval with waiver of
      informed patient consent. A preprocessing technique was previously proposed to
      improve the compressibility of CT images by replacing pixel values outside the
      body region with a constant value resulting in maximizing data redundancy. Since
      the technique was developed aiming at only chest CT images, the authors modified
      the segmentation method to cover the diversity of three dimensional
      configurations of different body parts. The modified version was evaluated as
      follows. In randomly selected 368 CT examinations (352,787 images), each image
      was preprocessed by using the modified preprocessing technique. Radiologists
      visually confirmed whether the segmented region covers the body region or not.
      The images with and without the preprocessing were reversibly compressed using
      Joint Photographic Experts Group (JPEG), JPEG2000 two-dimensional (2D), and
      JPEG2000 three-dimensional (3D) compressions. The percentage increase in CR per
      examination (CRI) was measured. RESULTS: The rate of correct segmentation was
      100.0% (95% CI: 99.9%, 100.0%) for all the examinations. The median of CRI were
      26.1% (95% CI: 24.9%, 27.1%), 40.2% (38.5%, 41.1%), and 34.5% (32.7%, 36.2%) in
      JPEG, JPEG2000 2D, and JPEG2000 3D, respectively. CONCLUSIONS: In various CT
      examinations, the modified preprocessing technique can increase in the CR by 25%
      or more without concerning about degradation of diagnostic information.

PMID- 24089913
TI  - Light wavelength effects in submicrometer phosphor materials using Mie scattering
      and Monte Carlo simulation.
AB  - PURPOSE: Phosphor materials provide challenges to both fundamental research and
      breakthrough development of technologies in research areas. In recent years, with
      the development of science and technology in the field of materials, a number of
      physical or chemical synthesis methods have been developed and successfully used
      for the preparation of submicrometer-sized phosphors. The present paper provides
      a rigorous analysis of light diffusion capabilities of phosphor materials in
      submicrometer-scale investigating the effect of light wavelength. METHODS: Mie
      scattering theory and Monte Carlo simulation techniques were used for the optical
      diffusion performance providing numerical calculations. The Monte Carlo model
      included: (i) phosphor layers composed of different thickness (200, 500, 1000
      MUm) and (ii) different light wavelength values (420, 545, 610 nm) corresponding
      to different types of activators, such as Ce, Tb, and Eu activators,
      respectively. RESULTS: Based on Mie calculations, it was found that for low
      values of refractive index (e.g., 1.4) and for particle radius from 250 up to 500
      nm no significant variations occurred on optical parameters. Monte Carlo
      simulations showed that the resolution increases as light wavelength decreases,
      respectively, however, this increase is more obvious at lower thickness values
      (i.e., at 200 MUm). In particular, as light wavelength decreases from 610 down to
      545 and 420 nm, the resolution increases 4.4% and 13.9%, respectively (at 200 MUm
      layer thickness). In addition, as layer thickness increases from 200 up to 500
      MUm the resolution decreases 50.2% while an increase up to 1000 MUm causes a
      decrease of 70.2% (at 420 nm light wavelength). CONCLUSIONS: The goal of the
      author's study was to investigate the optical diffusion characteristics of
      submicrometer phosphor materials using Mie scattering theory and Monte Carlo
      simulation. The present investigation indicated that a key parameter on
      resolution improvement was the amount of light loss which depends on the choice
      of activator and affects the lateral spreading.

PMID- 24089914
TI  - Simultaneous motion estimation and image reconstruction (SMEIR) for 4D cone-beam
      CT.
AB  - PURPOSE: Image reconstruction and motion model estimation in four-dimensional
      cone-beam CT (4D-CBCT) are conventionally handled as two sequential steps. Due to
      the limited number of projections at each phase, the image quality of 4D-CBCT is
      degraded by view aliasing artifacts, and the accuracy of subsequent motion
      modeling is decreased by the inferior 4D-CBCT. The objective of this work is to
      enhance both the image quality of 4D-CBCT and the accuracy of motion model
      estimation with a novel strategy enabling simultaneous motion estimation and
      image reconstruction (SMEIR). METHODS: The proposed SMEIR algorithm consists of
      two alternating steps: (1) model-based iterative image reconstruction to obtain a
      motion-compensated primary CBCT (m-pCBCT) and (2) motion model estimation to
      obtain an optimal set of deformation vector fields (DVFs) between the m-pCBCT and
      other 4D-CBCT phases. The motion-compensated image reconstruction is based on the
      simultaneous algebraic reconstruction technique (SART) coupled with total
      variation minimization. During the forward- and backprojection of SART, measured
      projections from an entire set of 4D-CBCT are used for reconstruction of the m
      pCBCT by utilizing the updated DVF. The DVF is estimated by matching the forward
      projection of the deformed m-pCBCT and measured projections of other phases of 4D
      CBCT. The performance of the SMEIR algorithm is quantitatively evaluated on a 4D
      NCAT phantom. The quality of reconstructed 4D images and the accuracy of tumor
      motion trajectory are assessed by comparing with those resulting from
      conventional sequential 4D-CBCT reconstructions (FDK and total variation
      minimization) and motion estimation (demons algorithm). The performance of the
      SMEIR algorithm is further evaluated by reconstructing a lung cancer patient 4D
      CBCT. RESULTS: Image quality of 4D-CBCT is greatly improved by the SMEIR
      algorithm in both phantom and patient studies. When all projections are used to
      reconstruct a 3D-CBCT by FDK, motion-blurring artifacts are present, leading to a
      24.4% relative reconstruction error in the NACT phantom. View aliasing artifacts
      are present in 4D-CBCT reconstructed by FDK from 20 projections, with a relative
      error of 32.1%. When total variation minimization is used to reconstruct 4D-CBCT,
      the relative error is 18.9%. Image quality of 4D-CBCT is substantially improved
      by using the SMEIR algorithm and relative error is reduced to 7.6%. The maximum
      error (MaxE) of tumor motion determined from the DVF obtained by demons
      registration on a FDK-reconstructed 4D-CBCT is 3.0, 2.3, and 7.1 mm along left
      right (L-R), anterior-posterior (A-P), and superior-inferior (S-I) directions,
      respectively. From the DVF obtained by demons registration on 4D-CBCT
      reconstructed by total variation minimization, the MaxE of tumor motion is
      reduced to 1.5, 0.5, and 5.5 mm along L-R, A-P, and S-I directions. From the DVF
      estimated by SMEIR algorithm, the MaxE of tumor motion is further reduced to 0.8,
      0.4, and 1.5 mm along L-R, A-P, and S-I directions, respectively. CONCLUSIONS:
      The proposed SMEIR algorithm is able to estimate a motion model and reconstruct
      motion-compensated 4D-CBCT. The SMEIR algorithm improves image reconstruction
      accuracy of 4D-CBCT and tumor motion trajectory estimation accuracy as compared
      to conventional sequential 4D-CBCT reconstruction and motion estimation.

PMID- 24089915
TI  - Artifact-resistant motion estimation with a patient-specific artifact model for
      motion-compensated cone-beam CT.
AB  - PURPOSE: In image-guided radiation therapy (IGRT) valuable information for
      patient positioning, dose verification, and adaptive treatment planning is
      provided by an additional kV imaging unit. However, due to the limited gantry
      rotation speed during treatment the typical acquisition time is quite long.
      Tomographic images of the thorax suffer from motion blurring or, if a gated 4D
      reconstruction is performed, from significant streak artifacts. Our purpose is to
      provide a method that reliably estimates respiratory motion in presence of severe
      artifacts. The estimated motion vector fields are then used for motion
      compensated image reconstruction to provide high quality respiratory-correlated
      4D volumes for on-board cone-beam CT (CBCT) scans. METHODS: The proposed motion
      estimation method consists of a model that explicitly addresses image artifacts
      because in presence of severe artifacts state-of-the-art registration methods
      tend to register artifacts rather than anatomy. Our artifact model, e.g.,
      generates streak artifacts very similar to those included in the gated 4D CBCT
      images, but it does not include respiratory motion. In combination with a
      registration strategy, the model gives an error estimate that is used to
      compensate the corresponding errors of the motion vector fields that are
      estimated from the gated 4D CBCT images. The algorithm is tested in combination
      with a cyclic registration approach using temporal constraints and with a
      standard 3D-3D registration approach. A qualitative and quantitative evaluation
      of the motion-compensated results was performed using simulated rawdata created
      on basis of clinical CT data. Further evaluation includes patient data which were
      scanned with an on-board CBCT system. RESULTS: The model-based motion estimation
      method is nearly insensitive to image artifacts of gated 4D reconstructions as
      they are caused by angular undersampling. The motion is accurately estimated and
      our motion-compensated image reconstruction algorithm can correct for it. Motion
      artifacts of 3D standard reconstruction are significantly reduced, while almost
      no new artifacts are introduced. CONCLUSIONS: Using the artifact model allows to
      accurately estimate and compensate for patient motion, even if the initial
      reconstructions are of very low image quality. Using our approach together with a
      cyclic registration algorithm yields a combination which shows almost no
      sensitivity to sparse-view artifacts and thus ensures both high spatial and high
      temporal resolution.

PMID- 24089916
TI  - Superficial dosimetry imaging based on Cerenkov emission for external beam
      radiotherapy with megavoltage x-ray beam.
AB  - PURPOSE: Cerenkov radiation emission occurs in all tissue, when charged particles
      (either primary or secondary) travel at velocity above the threshold for the
      Cerenkov effect (about 220 KeV in tissue for electrons). This study presents the
      first examination of optical Cerenkov emission as a surrogate for the absorbed
      superficial dose for MV x-ray beams. METHODS: In this study, Monte Carlo
      simulations of flat and curved surfaces were studied to analyze the energy
      spectra of charged particles produced in different regions near the surfaces when
      irradiated by MV x-ray beams. Cerenkov emission intensity and radiation dose were
      directly simulated in voxelized flat and cylindrical phantoms. The sampling
      region of superficial dosimetry based on Cerenkov radiation was simulated in
      layered skin models. Angular distributions of optical emission from the surfaces
      were investigated. Tissue mimicking phantoms with flat and curved surfaces were
      imaged with a time domain gating system. The beam field sizes (50 * 50-200 * 200
      mm(2)), incident angles (0 degrees -70 degrees ) and imaging regions were all
      varied. RESULTS: The entrance or exit region of the tissue has nearly homogeneous
      energy spectra across the beam, such that their Cerenkov emission is proportional
      to dose. Directly simulated local intensity of Cerenkov and radiation dose in
      voxelized flat and cylindrical phantoms further validate that this signal is
      proportional to radiation dose with absolute average discrepancy within 2%, and
      the largest within 5% typically at the beam edges. The effective sampling depth
      could be tuned from near 0 up to 6 mm by spectral filtering. The angular profiles
      near the theoretical Lambertian emission distribution for a perfect diffusive
      medium, suggesting that angular correction of Cerenkov images may not be required
      even for curved surface. The acquisition speed and signal to noise ratio of the
      time domain gating system were investigated for different acquisition procedures,
      and the results show there is good potential for real-time superficial dose
      monitoring. Dose imaging under normal ambient room lighting was validated, using
      gated detection and a breast phantom. CONCLUSIONS: This study indicates that
      Cerenkov emission imaging might provide a valuable way to superficial dosimetry
      imaging in real time for external beam radiotherapy with megavoltage x-ray beams.

PMID- 24089917
TI  - Cone beam breast CT with a high pitch (75 MUm), thick (500 MUm) scintillator CMOS
      flat panel detector: visibility of simulated microcalcifications.
AB  - PURPOSE: To measure and investigate the improvement of microcalcification (MC)
      visibility in cone beam breast CT with a high pitch (75 MUm), thick (500 MUm)
      scintillator CMOS/CsI flat panel detector (Dexela 2923, Perkin Elmer). METHODS:
      Aluminum wires and calcium carbonate grains of various sizes were embedded in a
      paraffin cylinder to simulate imaging of calcifications in a breast. Phantoms
      were imaged with a benchtop experimental cone beam CT system at various exposure
      levels. In addition to the Dexela detector, a high pitch (50 MUm), thin (150 MUm)
      scintillator CMOS/CsI flat panel detector (C7921CA-09, Hamamatsu Corporation,
      Hamamatsu City, Japan) and a widely used low pitch (194 MUm), thick (600 MUm)
      scintillator aSi/CsI flat panel detector (PaxScan 4030CB, Varian Medical Systems)
      were also used in scanning for comparison. The images were independently reviewed
      by six readers (imaging physicists). The MC visibility was quantified as the
      fraction of visible MCs and measured as a function of the estimated mean
      glandular dose (MGD) level for various MC sizes and detectors. The modulation
      transfer functions (MTFs) and detective quantum efficiencies (DQEs) were also
      measured and compared for the three detectors used. RESULTS: The authors have
      demonstrated that the use of a high pitch (75 MUm) CMOS detector coupled with a
      thick (500 MUm) CsI scintillator helped make the smaller 150-160, 160-180, and
      180-200 MUm MC groups more visible at MGDs up to 10.8, 9, and 10.8 mGy,
      respectively. It also made the larger 200-212 and 212-224 MUm MC groups more
      visible at MGDs up to 7.2 mGy. No performance improvement was observed for 224
      250 MUm or larger size groups. With the higher spatial resolution of the Dexela
      detector based system, the apparent dimensions and shapes of MCs were more
      accurately rendered. The results show that with the aforementioned detector, a
      73% visibility could be achieved in imaging 160-180 MUm MCs as compared to 28%
      visibility achieved by the low pitch (194 MUm) aSi/CsI flat panel detector. The
      measurements confirm that the Hamamatsu detector has the highest MTF, followed by
      the Dexel detector, and then the Varian detector. However, the Dexela detector,
      with its thick (500 MUm) CsI scintillator and low noise level, has the highest
      DQE at all frequencies, followed by the Varian detector, and then the Hamamatsu
      detector. The findings on the MC visibility correlated well with the differences
      in MTFs, noise power spectra, and DQEs measured for these three detectors.
      CONCLUSIONS: The authors have demonstrated that the use of the CMOS type Dexela
      detector with its high pitch (75 MUm) and thick (500 MUm) CsI scintillator could
      help improve the MC visibility. However, the improvement depended on the exposure
      level and the MC size. For imaging larger MCs or scanning at high exposure
      levels, there was little advantage in using the Dexela detector as compared to
      the aSi type Varian detector. These findings correlate well with the higher
      measured DQEs of the Dexela detector, especially at higher frequencies.

PMID- 24089918
TI  - Effective detective quantum efficiency for two mammography systems: measurement
      and comparison against established metrics.
AB  - PURPOSE: The aim of this paper was to illustrate the value of the new metric
      effective detective quantum efficiency (eDQE) in relation to more established
      measures in the optimization process of two digital mammography systems. The
      following metrics were included for comparison against eDQE: detective quantum
      efficiency (DQE) of the detector, signal difference to noise ratio (SdNR), and
      detectability index (d') calculated using a standard nonprewhitened observer with
      eye filter. METHODS: The two systems investigated were the Siemens MAMMOMAT
      Inspiration and the Hologic Selenia Dimensions. The presampling modulation
      transfer function (MTF) required for the eDQE was measured using two geometries:
      a geometry containing scattered radiation and a low scatter geometry. The eDQE,
      SdNR, and d' were measured for poly(methyl methacrylate) (PMMA) thicknesses of
      20, 40, 60, and 70 mm, with and without the antiscatter grid and for a selection
      of clinically relevant target/filter (T/F) combinations. Figures of merit (FOMs)
      were then formed from SdNR and d' using the mean glandular dose as the factor to
      express detriment. Detector DQE was measured at energies covering the range of
      typical clinically used spectra. RESULTS: The MTF measured in the presence of
      scattered radiation showed a large drop at low spatial frequency compared to the
      low scatter method and led to a corresponding reduction in eDQE. The eDQE for the
      Siemens system at 1 mm(-1) ranged between 0.15 and 0.27, depending on T/F and
      grid setting. For the Hologic system, eDQE at 1 mm(-1) varied from 0.15 to 0.32,
      again depending on T/F and grid setting. The eDQE results for both systems showed
      that the grid increased the system efficiency for PMMA thicknesses of 40 mm and
      above but showed only small sensitivity to T/F setting. While results of the SdNR
      and d' based FOMs confirmed the eDQE grid position results, they were also more
      specific in terms of T/F selection. For the Siemens system at 20 mm PMMA, the
      FOMs indicated Mo/Mo (grid out) as optimal while W/Rh (grid in) was the optimal
      configuration at 40, 60, and 70 mm PMMA. For the Hologic, the FOMs pointed to
      W/Rh (grid in) at 20 and 40 mm of PMMA while W/Ag (grid in) gave the highest FOM
      at 60 and 70 mm PMMA. Finally, DQE at 1 mm(-1) averaged for the four beam
      qualities studied was 0.44 +/- 0.02 and 0.55 +/- 0.03 for the Siemens and Hologic
      detectors, respectively, indicating only a small influence of energy on detector
      DQE. CONCLUSIONS: Both the DQE and eDQE data showed only a small sensitivity to
      T/F setting for these two systems. The eDQE showed clear preferences in terms of
      scatter reduction, being highest for the grid-in geometry for PMMA thicknesses of
      40 mm and above. The SdNR and d' based figures of merit, which contain additional
      weighting for contrast and dose, pointed to specific T/F settings for both
      systems.

PMID- 24089919
TI  - Proton radiography in three dimensions: a proof of principle of a new technique.
AB  - PURPOSE: Monte Carlo simulations were used to investigate a range of phantom
      configurations to establish enabling three-dimensional proton radiographic
      techniques. METHODS: A large parameter space of stacked phantom geometries
      composed of tissue inhomogeneity materials such as lung, bone, and cartilage
      inserted within water background were simulated using a purposefully modified
      version of TOPAS, an application running on top of the GEANT4 Monte Carlo code.
      The phantoms were grouped in two classes, one with the inhomogeneity inserted
      only half-way in the lateral direction and another with complete inhomogeneity
      insertion. The former class was used to calculate the track count and the energy
      fluence of the protons as they exit the phantoms either having traversed the
      inhomogeneity or not. The latter class was used to calculate one yield value
      accounting for loss of protons due to physical processes only and another yield
      value accounting for deliberately discarded protons due to large scattering
      angles. A graphical fingerprinting method was developed to determine the
      inhomogeneity thickness and location within the phantom based on track count and
      energy fluence information. Two additional yield values extended this method to
      the general case which also determines the inhomogeneity material and the phantom
      thickness. RESULTS: The graphical fingerprinting method was manually validated
      for two, and automatically tested for all, tissue materials using an exhaustive
      set of inhomogeneity geometries for 16 cm thick phantoms. Unique recognition of
      test phantom configurations was achieved in the large majority of cases. The
      method in the general case was further tested using an exhaustive set of
      inhomogeneity and phantom tissues and geometries where the phantom thicknesses
      ranged between 8 and 24 cm. Unique recognition of the test phantom configurations
      was achieved only for part of the phantom parameter space. The correlations
      between the remaining false positive recognitions were analyzed. CONCLUSIONS: The
      concept of 3D proton radiography for tissue inhomogeneities of simple geometries
      was established with the current work. In contrast to conventional 2D proton
      radiography, the main objective of the demonstrated 3D technique is not proton
      range. Rather, it is to measure the depth and thickness of an inhomogeneity
      located in an imaged geometry. Further work is needed to extend and apply the
      method to more complex geometries.

PMID- 24089920
TI  - Mineralization in calcified plaque is like that of cortical bone--further
      evidence from ultrashort echo time (UTE) magnetic resonance imaging of carotid
      plaque calcification and cortical bone.
AB  - PURPOSE: This study aims to investigate carotid plaque calcification (CPC) using
      two-dimensional (2D) and 3D ultrashort echo time (UTE) magnetic resonance imaging
      (MRI) sequences and compare T1, T2*, water concentration, and bone mineral
      density (BMD) of CPC with those of cortical bone. METHODS: Twelve carotid plaque
      specimens and eight tibial cortical bone samples were imaged with UTE sequences.
      Adiabatic inversion recovery prepared UTE (IR-UTE) acquisitions were used for T2*
      measurement. Saturation recovery prepared UTE acquisitions were used for T1
      measurement. Water concentration was measured by comparing signal from CPC and
      bone with that from a phantom. BMD was measured with MUCT. Conventional gradient
      echo and fast spin echo images were also acquired for comparison. RESULTS: Our
      studies show that CPC and cortical bone have similar T1 and BMD values but
      different T2* and water concentration. For CPC T2*s ranged from 0.31 to 3.87 ms,
      T1s ranged from 114 to 332 ms, water concentrations ranged from 6.4% to 17.6%,
      and BMD ranged from 977 to 1319 mg/ml. For cortical bone T2*s ranged from 0.33 to
      0.45 ms, T1s ranged from 198 to 254 ms, water concentrations ranged from 24.7% to
      33.8%, and mineral densities ranged from 970 to 1287 mg/ml. On average CPC shows
      about 5% longer T1, 5% lower BMD, 440% longer T2*, and 130% lower water
      concentration when compared to human cortical bone. CONCLUSIONS: CPC bears
      remarkable similarities with cortical bone in terms of BMD and T1. CPC shows a
      higher mean T2* and a lower mean water concentration.

PMID- 24089921
TI  - A slice-to-volume registration method based on real-time magnetic resonance
      imaging for measuring three-dimensional kinematics of the knee.
AB  - PURPOSE: This study developed and assessed a slice-to-volume registration method
      that integrated three-dimensional (3D) static MRI volumes of the bones with a
      novel single-slice, real-time radial fast low-angle shot MRI for measuring the 3D
      kinematics of the knee. METHODS: Multislice 3D images (for establishing bone
      models) and 2D real-time images of the knee at five static positions, and 2D real
      time images of the knee during flexion/extension were acquired from three healthy
      adults. The 3D bone poses, and thus the 3D kinematics of the knee, were obtained
      by registering the real-time images to a reformed slice interpolated from the
      bone models according to the WEMS similarity measure. The ensemble means (biases)
      and standard deviations (precisions) of the measurement errors of the proposed
      measurement method, i.e., differences between the 3D images and the registered
      poses, were calculated across all the static trials of all subjects. Ensemble
      standard deviations of all the repeated registrations for the dynamic data of all
      subjects were obtained to indicate the repeatability of the registration method.
      RESULTS: The ensemble means (standard deviations) of the measurement errors of
      the femoral poses were less than 0.6 (0.6) mm for translations and -0.2 degrees 
      (1.3 degrees ) degrees for rotations. The corresponding values for the tibia were
      0.5 (0.7) mm and -0.4 degrees  (1.1 degrees ), respectively. The ensemble means
      (standard deviations) of the measurement errors of knee joint poses were less
      than 0.9 (1.4) mm for translations and -0.3 degrees  (1.8 degrees ) degrees for
      rotations. For registration repeatability of dynamic tests, the ensemble standard
      deviations were all less than 1.2 mm for translations and 1.5 degrees  for
      rotations. CONCLUSIONS: With the accuracy and repeatability achieved, and without
      the use of ionizing radiation and multiple repetitive motions, the proposed
      method combining the novel real-time MR imaging promises to be a valuable tool
      for studying 3D knee kinematics noninvasively.

PMID- 24089922
TI  - Direct reconstruction of cardiac PET kinetic parametric images using a
      preconditioned conjugate gradient approach.
AB  - PURPOSE: Our research goal is to develop an algorithm to reconstruct cardiac
      positron emission tomography (PET) kinetic parametric images directly from
      sinograms and compare its performance with the conventional indirect approach.
      METHODS: Time activity curves of a NCAT phantom were computed according to a one
      tissue compartmental kinetic model with realistic kinetic parameters. The
      sinograms at each time frame were simulated using the activity distribution for
      the time frame. The authors reconstructed the parametric images directly from the
      sinograms by optimizing a cost function, which included the Poisson log
      likelihood and a spatial regularization terms, using the preconditioned conjugate
      gradient (PCG) algorithm with the proposed preconditioner. The proposed
      preconditioner is a diagonal matrix whose diagonal entries are the ratio of the
      parameter and the sensitivity of the radioactivity associated with parameter. The
      authors compared the reconstructed parametric images using the direct approach
      with those reconstructed using the conventional indirect approach. RESULTS: At
      the same bias, the direct approach yielded significant relative reduction in
      standard deviation by 12%-29% and 32%-70% for 50 * 10(6) and 10 * 10(6) detected
      coincidences counts, respectively. Also, the PCG method effectively reached a
      constant value after only 10 iterations (with numerical convergence achieved
      after 40-50 iterations), while more than 500 iterations were needed for CG.
      CONCLUSIONS: The authors have developed a novel approach based on the PCG
      algorithm to directly reconstruct cardiac PET parametric images from sinograms,
      and yield better estimation of kinetic parameters than the conventional indirect
      approach, i.e., curve fitting of reconstructed images. The PCG method increases
      the convergence rate of reconstruction significantly as compared to the
      conventional CG method.

PMID- 24089923
TI  - Pediatric radiation dosimetry for positron-emitting radionuclides using
      anthropomorphic phantoms.
AB  - PURPOSE: Positron emission tomography (PET) plays an important role in the
      diagnosis, staging, treatment, and surveillance of clinically localized diseases.
      Combined PET/CT imaging exhibits significantly higher sensitivity, specificity,
      and accuracy than conventional imaging when it comes to detecting malignant
      tumors in children. However, the radiation dose from positron-emitting
      radionuclide to the pediatric population is a matter of concern since children
      are at a particularly high risk when exposed to ionizing radiation. METHODS: The
      authors evaluate the absorbed fractions and specific absorbed fractions (SAFs) of
      monoenergy photons/electrons as well as S-values of 9 positron-emitting
      radionuclides (C-11, N-13, O-15, F-18, Cu-64, Ga-68, Rb-82, Y-86, and I-124) in
      48 source regions for 10 anthropomorphic pediatric hybrid models, including the
      reference newborn, 1-, 5-, 10-, and 15-yr-old male and female models, using the
      Monte Carlo N-Particle eXtended general purpose Monte Carlo transport code.
      RESULTS: The self-absorbed SAFs and S-values for most organs were inversely
      related to the age and body weight, whereas the cross-dose terms presented less
      correlation with body weight. For most source/target organ pairs, Rb-82 and Y-86
      produce the highest self-absorbed and cross-absorbed S-values, respectively,
      while Cu-64 produces the lowest S-values because of the low-energy and high
      frequency of electron emissions. Most of the total self-absorbed S-values are
      contributed from nonpenetrating particles (electrons and positrons), which have a
      linear relationship with body weight. The dependence of self-absorbed S-values of
      the two annihilation photons varies to the reciprocal of 0.76 power of the mass,
      whereas the self-absorbed S-values of positrons vary according to the reciprocal
      mass. CONCLUSIONS: The produced S-values for common positron-emitting
      radionuclides can be exploited for the assessment of radiation dose delivered to
      the pediatric population from various PET radiotracers used in clinical and
      research settings. The mass scaling method for positron-emitters can be used to
      derive patient-specific S-values from data of reference phantoms.

PMID- 24089924
TI  - Evaluation of motion correction methods in human brain PET imaging--a simulation
      study based on human motion data.
AB  - PURPOSE: Motion correction in PET has become more important as system resolution
      has improved. The purpose of this study was to evaluate the accuracy of event-by
      event and frame-based MC methods in human brain PET imaging. METHODS: Motion
      compensated image reconstructions were performed with static and dynamic
      simulated high resolution research tomograph data with frame-based image
      reconstructions, using a range of measured human head motion data. Image
      intensities in high-contrast regions of interest (ROI) and parameter estimates in
      tracer kinetic models were assessed to evaluate the accuracy of the motion
      correction methods. RESULTS: Given accurate motion data, event-by-event motion
      correction can reliably correct for head motions. The average ROI intensities and
      the kinetic parameter estimates VT and BPND were comparable to the true values.
      The frame-based motion correction methods with correctly aligned attenuation map
      using the average of externally acquired motion data or motion data derived from
      image registration give comparable quantitative accuracy. For large intraframe
      (>5 mm) motion, the frame-based methods produced ~ 9% bias in ROI intensities, ~
      5% in VT, and ~ 10% in BPND estimates. In addition, in real studies that lack a
      ground truth, the normalized weighted residual sum of squared difference is a
      potential figure-of-merit to evaluate the accuracy of motion correction methods.
      CONCLUSIONS: The authors conclude that frame-based motion correction methods are
      accurate when the intraframe motion is less than 5 mm and when the attenuation
      map is accurately aligned. Given accurate motion data, event-by-event motion
      correction can reliably correct for head motion in human brain PET studies.

PMID- 24089925
TI  - Molecular radiotherapy: the NUKFIT software for calculating the time-integrated
      activity coefficient.
AB  - PURPOSE: Calculation of the time-integrated activity coefficient (residence time)
      is a crucial step in dosimetry for molecular radiotherapy. However, available
      software is deficient in that it is either not tailored for the use in molecular
      radiotherapy and/or does not include all required estimation methods. The aim of
      this work was therefore the development and programming of an algorithm which
      allows for an objective and reproducible determination of the time-integrated
      activity coefficient and its standard error. METHODS: The algorithm includes the
      selection of a set of fitting functions from predefined sums of exponentials and
      the choice of an error model for the used data. To estimate the values of the
      adjustable parameters an objective function, depending on the data, the
      parameters of the error model, the fitting function and (if required and
      available) Bayesian information, is minimized. To increase reproducibility and
      user-friendliness the starting values are automatically determined using a
      combination of curve stripping and random search. Visual inspection, the
      coefficient of determination, the standard error of the fitted parameters, and
      the correlation matrix are provided to evaluate the quality of the fit. The
      functions which are most supported by the data are determined using the corrected
      Akaike information criterion. The time-integrated activity coefficient is
      estimated by analytically integrating the fitted functions. Its standard error is
      determined assuming Gaussian error propagation. The software was implemented
      using MATLAB. RESULTS: To validate the proper implementation of the objective
      function and the fit functions, the results of NUKFIT and SAAM numerical, a
      commercially available software tool, were compared. The automatic search for
      starting values was successfully tested for reproducibility. The quality criteria
      applied in conjunction with the Akaike information criterion allowed the
      selection of suitable functions. Function fit parameters and their standard error
      estimated by using SAAM numerical and NUKFIT showed differences of <1%. The
      differences for the time-integrated activity coefficients were also <1% (standard
      error between 0.4% and 3%). In general, the application of the software is user
      friendly and the results are mathematically correct and reproducible. An
      application of NUKFIT is presented for three different clinical examples.
      CONCLUSIONS: The software tool with its underlying methodology can be employed to
      objectively and reproducibly estimate the time integrated activity coefficient
      and its standard error for most time activity data in molecular radiotherapy.

PMID- 24089926
TI  - A novel approach for direct reconstruction of parametric images for myocardial
      blood flow from PET imaging.
AB  - PURPOSE: The aim of this study is to develop and evaluate a novel direct
      reconstruction method to improve the signal-to-noise ratio (SNR) of parametric
      images in dynamic positron-emission tomography (PET), especially for applications
      in myocardial perfusion studies. METHODS: Simulation studies were used to test
      the performance in SNR and computational efficiency for different methods. The
      NCAT phantom was used to generate simulated dynamic data. Noise realization was
      performed in the sinogram domain and repeated for 30 times with four different
      noise levels by varying the injection dose (ID) from standard ID to 1/8 of it.
      The parametric images were calculated by (1) three direct methods that compute
      the kinetic parameters from the sinogram and (2) an indirect method, which
      computes the kinetic parameter with pixel-by-pixel curve fitting in image space
      using weighted least-squares. The first direct reconstruction maximizes the
      likelihood function using trust-region-reflective (TRR) algorithm. The second
      approach uses tabulated parameter sets to generate precomputed time-activity
      curves for maximizing the likelihood functions. The third approach, as a newly
      proposed method, assumes separable complete data to derive the M-step for
      maximizing the likelihood. RESULTS: The proposed method with the separable
      complete data performs similarly to the other two direct reconstruction methods
      in terms of the SNR, providing a 5%-10% improvement as compared to the indirect
      parametric reconstruction under the standard ID. The improvement of SNR becomes
      more obvious as the noise level increases, reaching more than 30% improvement
      under 1/8 ID. Advantage of the proposed method lies in the computation efficiency
      by shortening the time requirement to 25% of the indirect approach and 3%-6% of
      other direct reconstruction methods. CONCLUSIONS: With results provided from this
      simulation study, direct reconstruction of myocardial blood flow shows a high
      potential for improving the parametric image quality for clinical use.

PMID- 24089927
TI  - Simultaneous 99mTc-MDP/123I-MIBG tumor imaging using SPECT-CT: phantom and
      constructed patient studies.
AB  - PURPOSE: Authors' goal is to evaluate the performance of simultaneous (99m)Tc
      MDP/(123)I-MIBG tumor imaging with fast Monte-Carlo (MC) based joint iterative
      reconstruction as compared to sequential (99m)Tc-MDP and (123)I-MIBG tumor
      imaging. METHODS: Noise-free (99m)Tc and (123)I SPECT projections were acquired
      separately using an anthropomorphic torso phantom modified to include a fillable
      tube around the lungs to mimic ribs. Additionally, (99m)Tc and (123)I projections
      were acquired separately using a 1-cm spherical "tumor" placed at various
      distances from one detector. Tumor-present data were generated by adding tumor
      projections to the torso phantom data, which were scaled to the total counts in
      typical clinical studies. Twenty-five noise realizations were generated by adding
      Poisson noise to the projection data for each radionuclide. Dual-radionuclide
      data were synthesized by summing the (99m)Tc and (123)I projections. Image
      reconstruction was performed using: (1) SR-OSEM, ordered subset expectation
      maximization (OSEM) without scatter correction (SC) using single-radionuclide
      (SR) data; (2) SR-MC-OSEM, OSEM with a fast MC-based SC using SR data; (3) DR
      OSEM, OSEM without SC using dual-radionuclide (DR) data; and (4) DR-MC-JOSEM,
      joint OSEM with a fast MC-based SC using DR data. Ten (99m)Tc-MDP and ten (123)I
      MIBG data sets, which had tumors mathematically inserted, were also used to
      evaluate the performance of authors' approach. For the phantom study, relative
      bias and relative standard deviation of tumor uptake were computed for each tumor
      using the tumor uptake in the noise-free single-radionuclide images, which were
      reconstructed by SR-MC-OSEM, as the gold standard. For both the phantom and
      constructed patient studies, mean contrast and standard deviation of contrast
      were computed for each tumor for both the single- and dual-radionuclide images.
      Additionally, contrast recovery was computed as the ratio between mean contrast
      and the mean contrast for SR-MC-OSEM. RESULTS: For the phantom study, DR-MC-JOSEM
      yielded 2.7% on average relative bias of tumor uptake using the images, which
      were reconstructed from the noise-free SR data with SR-MC-OSEM, as the gold
      standard. For both the phantom and constructed patient studies, DR-MC-JOSEM
      yielded 94.7% and 95.2% tumor contrast recovery on average using SR-MC-OSEM as
      the reference, in the phantom and constructed patient studies, respectively. DR
      MC-JOSEM yielded comparable relative standard deviation of bias and standard
      deviation of contrast to SR-MC-OSEM. CONCLUSIONS: Simultaneous (99m)Tc-MDP/(123)I
      MIBG tumor imaging using authors' dual-radionuclide reconstruction approach
      yielded comparable image quality to sequential (99m)Tc-MDP and (123)I-MIBG
      imaging. For patients who need to undergo both scans, authors' approach offers
      perfectly registered dual-tracer images under identical conditions without
      compromising image quality, and reduces the imaging cost while increasing patient
      throughput.

PMID- 24089928
TI  - Low dose interpolated average CT for thoracic PET/CT attenuation correction using
      an active breathing controller.
AB  - PURPOSE: The temporal mismatch between PET and standard helical CT (HCT) causes
      substantial respiratory artifacts in PET reconstructed images when using HCT as
      the attenuation map. Previously we developed an interpolated average CT (IACT)
      method for attenuation correction (AC) and demonstrated its merits in
      simulations. In this study we aim to apply IACT in patients with thoracic lesions
      using an active breathing controller (ABC). METHODS: Under local ethics approval,
      we recruited 15 patients with a total of 18 lesions in different thoracic
      regions: left upper lobe (2), right upper lobe (4), right hilum (3), right lower
      lobe (3), left hilum (2), and esophagus (4). All patients underwent whole body
      PET scans 1 h after 300-480 MBq (18)F-FDG injection, depending on the patients'
      weight. The PET sinograms were reconstructed with AC using: (i) standard HCT [120
      kV, smart mA (30-150 mA), 0.984:1 pitch] and (ii) IACT obtained from end
      inspiration and end-expiration breath-hold HCTs (120 kV, 10 mA, 0.984:1 pitch)
      aided by ABC. IACT was obtained by averaging the intensity of two extreme phases
      and the interpolated phases between them, where the nonlinear interpolation was
      obtained by B-spline registration and with an empirical sinusoidal function. The
      SUV max, SUV mean, and the differences of centroid-of-lesion (d) between PET and
      different CT schemes were measured for each lesion. RESULTS: From visual
      inspection, the respiratory artifacts and blurring generally reduced in the
      thoracic region for PET IACT. Matching between CT and PET improved for PET IACT,
      with an average decrease of d for 1.34 +/- 1.79 mm as compared to PET HCT. The
      SUV max and SUV mean were consistently higher for PET IACT versus PET HCT for all
      lesions, with (30.95 +/- 18.63)% and (22.39 +/- 15.91)% average increase,
      respectively. CONCLUSIONS: IACT-ABC reduces respiratory artifacts, PET/CT
      misregistration and enhances lesion quantitation. This technique is a robust and
      low dose AC protocol for clinical oncology application especially in the thoracic
      region.

PMID- 24089929
TI  - Automatic detection of microcalcifications in breast ultrasound.
AB  - PURPOSE: In an ultrasound (US) image, the presence of microcalcifications within
      breast lesions is an important indicator of malignancy. The purpose of this study
      was to develop a novel automatic detection system to find microcalcifications
      inside a breast lesion using an US image. METHODS: Breast US images from 103
      cases with microcalcifications were obtained using an US system with a 6-14 MHz
      transducer, and 585 microcalcification foci marked on 103 breast US images by a
      radiologist were used as the ground truth. After segmentation of the lesion
      contour using the level set method, the microcalcification candidates inside the
      lesion were found using adaptive speckle reduction and top hat filters. Then,
      three criteria were used to identify the real microcalcifications, including the
      mean, single point, and brightness criteria. RESULTS: The proposed method
      revealed microcalcifications within the lesions in all 103 cases. The sensitivity
      and the false positive (FP) rate for the detection of microcalcification foci
      were 80.3% (470/585) and 3.1 per case, respectively. The sensitivities and FP
      rates for the benign and malignant cases were 79.2% (243/307) with a FP rate of
      3.5 and 81.7% (227/278) with a FP rate of 2.6, respectively. CONCLUSIONS: The
      authors' proposed method has the potential to provide a tool to help physicians
      detect microcalcifications within breast lesions.

PMID- 24089930
TI  - Integration of microwave tomography with magnetic resonance for improved breast
      imaging.
AB  - PURPOSE: Breast magnetic resonance imaging is highly sensitive but not very
      specific for the detection of breast cancer. Opportunities exist to supplement
      the image acquisition with a more specific modality provided the technical
      challenges of meeting space limitations inside the bore, restricted breast
      access, and electromagnetic compatibility requirements can be overcome. Magnetic
      resonance (MR) and microwave tomography (MT) are complementary and synergistic
      because the high resolution of MR is used to encode spatial priors on breast
      geometry and internal parenchymal features that have distinct electrical
      properties (i.e., fat vs fibroglandular tissue) for microwave tomography.
      METHODS: The authors have overcome integration challenges associated with
      combining MT with MR to produce a new coregistered, multimodality breast imaging
      platform--magnetic resonance microwave tomography, including: substantial
      illumination tank size reduction specific to the confined MR bore diameter,
      minimization of metal content and composition, reduction of metal artifacts in
      the MR images, and suppression of unwanted MT multipath signals. RESULTS: MR SNR
      exceeding 40 dB can be obtained. Proper filtering of MR signals reduces MT data
      degradation allowing MT SNR of 20 dB to be obtained, which is sufficient for
      image reconstruction. When MR spatial priors are incorporated into the recovery
      of MT property estimates, the errors between the recovered versus actual
      dielectric properties approach 5%. CONCLUSIONS: The phantom and human subject
      exams presented here are the first demonstration of combining MT with MR to
      improve the accuracy of the reconstructed MT images.

PMID- 24089931
TI  - Optimization in interstitial plasmonic photothermal therapy for treatment
      planning.
AB  - PURPOSE: Gold nanorods have the potential to enhance the treatment efficacy of
      interstitial photothermal therapy. In order to enhance both the potential
      efficiency and the safety of such procedures, treatment planning on laser power
      density, nanoparticle concentration, and exposure time has turned out to be
      useful in predicting the thermal damage and optimizing treatment outcome. To the
      best of our knowledge, there is no previous report on the optimization of
      interstitial plasmonic photothermal therapy (PPTT) for all these free parameters
      simultaneously. The authors propose to develop a suitable optimization algorithm
      for interstitial PPTT to optimize these parameters and achieve complete damage to
      spherical tumors of different sizes with a damage margin width of 1 mm from the
      tumor boundary embedded deep inside a normal tissue model. METHODS: In a
      numerical tissue model, the standard Pennes bioheat equation and the first-order
      thermal-chemical rate equation were used to model the temperature and thermal
      damage distributions, respectively, in spherical tumors that were embedded deep
      inside a normal tissue and incubated with nanorods. The concentration of nanorods
      in the normal tissue was set to be about one quarter of that in the tumor.
      Thermal damage due to varying concentrations of nanorods, laser power density,
      and exposure time was computed for a series of tumor radii including 2, 3, 4, and
      5 mm. An optimization algorithm was developed to determine the optimum laser
      power density, nanorod concentration, and exposure time for the treatment of such
      spherical tumors. In this algorithm, a novel objective function was created to
      enable the optimization of multiple key parameters, including nanoparticle
      concentration, power density, and exposure time, simultaneously to achieve not
      only the complete thermal damage to the entire tumor but also the collateral
      damage to the surrounding normal tissue with a margin width of 1 mm from the
      tumor boundary. Different weights were assigned sequentially to each free
      parameter according to the relative importance of the parameters. A thermal
      damage value of one calculated by Arrhenius damage law, which is more accurate
      than a threshold temperature typically used for characterizing thermal damage,
      was used to indicate effective treatment. RESULTS: The simulation results show
      that there is a steady increase in the overall temperature as the nanorod
      concentration increases; however, the uniformity of the temperature distribution
      changes significantly which in turn affects the thermal damage. Optimization
      results show that any slight decrease in one free parameter can be compensated by
      the increase in other free parameters, in which the complete thermal damage of
      the tumor and the collateral damage to normal tissue with a margin width of 1 mm
      can be always achieved. This implies the importance of optimization in
      interstitial PPTT. CONCLUSIONS: The proposed method can optimize laser power
      density, nanoparticle concentration, and exposure time simultaneously with
      different weights in interstitial PPTT planning for deep seated tumors. It
      provides flexibility for a clinician to make appropriate planning for individual
      patients according to their special needs.

PMID- 24089933
TI  - Fast thermal simulations and temperature optimization for hyperthermia treatment
      planning, including realistic 3D vessel networks.
AB  - PURPOSE: Accurate thermal simulations in hyperthermia treatment planning require
      discrete modeling of large blood vessels. The very long computation time of the
      finite difference based DIscrete VAsculature model (DIVA) developed for this
      purpose is impractical for clinical applications. In this work, a fast steady
      state thermal solver was developed for simulations with realistic 3D vessel
      networks. Additionally, an efficient temperature-based optimization method
      including the thermal effect of discrete vasculature was developed. METHODS: The
      steady-state energy balance for vasculature and tissue was described by a linear
      system, which was solved with an iterative method on the graphical processing
      unit. Temperature calculations during optimization were performed by
      superposition of several precomputed temperature distributions, calculated with
      the developed thermal solver. The thermal solver and optimization were applied to
      a human anatomy, with the prostate being the target region, heated with the eight
      waveguide 70 MHz AMC-8 system. Realistic 3D pelvic vasculature was obtained from
      angiography. Both the arterial and venous vessel networks consisted of 174
      segments and 93 endpoints with a diameter of 1.2 mm. RESULTS: Calculation of the
      steady-state temperature distribution lasted about 3.3 h with the original DIVA
      model, while the newly developed method took only ~ 1-1.5 min. Temperature-based
      optimization with and without taking the vasculature into account showed
      differences in optimized waveguide power of more than a factor 2 and optimized
      tumor T90 differed up to ~ 0.5 degrees C. This shows the necessity to take
      discrete vasculature into account during optimization. CONCLUSIONS: A very fast
      method was developed for thermal simulations with realistic 3D vessel networks.
      The short simulation time allows online calculations and makes temperature
      optimization with realistic vasculature feasible, which is an important step
      forward in hyperthermia treatment planning.

PMID- 24089932
TI  - Multiparametric fat-water separation method for fast chemical-shift imaging
      guidance of thermal therapies.
AB  - PURPOSE: A k-means-based classification algorithm is investigated to assess
      suitability for rapidly separating and classifying fat/water spectral peaks from
      a fast chemical shift imaging technique for magnetic resonance temperature
      imaging. Algorithm testing is performed in simulated mathematical phantoms and
      agar gel phantoms containing mixed fat/water regions. METHODS: Proton resonance
      frequencies (PRFs), apparent spin-spin relaxation (T2*) times, and T1-weighted
      (T1-W) amplitude values were calculated for each voxel using a single-peak
      autoregressive moving average (ARMA) signal model. These parameters were then
      used as criteria for k-means sorting, with the results used to determine PRF
      ranges of each chemical species cluster for further classification. To detect the
      presence of secondary chemical species, spectral parameters were recalculated
      when needed using a two-peak ARMA signal model during the subsequent
      classification steps. Mathematical phantom simulations involved the modulation of
      signal-to-noise ratios (SNR), maximum PRF shift (MPS) values, analysis window
      sizes, and frequency expansion factor sizes in order to characterize the
      algorithm performance across a variety of conditions. In agar, images were
      collected on a 1.5T clinical MR scanner using acquisition parameters close to
      simulation, and algorithm performance was assessed by comparing classification
      results to manually segmented maps of the fat/water regions. RESULTS: Performance
      was characterized quantitatively using the Dice Similarity Coefficient (DSC),
      sensitivity, and specificity. The simulated mathematical phantom experiments
      demonstrated good fat/water separation depending on conditions, specifically high
      SNR, moderate MPS value, small analysis window size, and low but nonzero
      frequency expansion factor size. Physical phantom results demonstrated good
      identification for both water (0.997 +/- 0.001, 0.999 +/- 0.001, and 0.986 +/-
      0.001 for DSC, sensitivity, and specificity, respectively) and fat (0.763 +/-
      0.006, 0.980 +/- 0.004, and 0.941 +/- 0.002 for DSC, sensitivity, and
      specificity, respectively). Temperature uncertainties, based on PRF uncertainties
      from a 5 * 5-voxel ROI, were 0.342 and 0.351 degrees C for pure and mixed
      fat/water regions, respectively. Algorithm speed was tested using 25 * 25-voxel
      and whole image ROIs containing both fat and water, resulting in average
      processing times per acquisition of 2.00 +/- 0.07 s and 146 +/- 1 s,
      respectively, using uncompiled MATLAB scripts running on a shared CPU server with
      eight Intel Xeon(TM) E5640 quad-core processors (2.66 GHz, 12 MB cache) and 12 GB
      RAM. CONCLUSIONS: Results from both the mathematical and physical phantom suggest
      the k-means-based classification algorithm could be useful for rapid, dynamic
      imaging in an ROI for thermal interventions. Successful separation of fat/water
      information would aid in reducing errors from the nontemperature sensitive fat
      PRF, as well as potentially facilitate using fat as an internal reference for PRF
      shift thermometry when appropriate. Additionally, the T1-W or R2* signals may be
      used for monitoring temperature in surrounding adipose tissue.

PMID- 24089934
TI  - A framework to measure myocardial extracellular volume fraction using dual-phase
      low dose CT images.
AB  - PURPOSE: Myocardial extracellular volume fraction (ECVF) is a surrogate imaging
      biomarker of diffuse myocardial fibrosis, a hallmark of pathologic ventricular
      remodeling. Low dose cardiac CT is emerging as a promising modality to detect
      diffuse interstitial myocardial fibrosis due to its fast acquisition and low
      radiation; however, the insufficient contrast in the low dose CT images poses
      great challenge to measure ECVF from the image. METHODS: To deal with this
      difficulty, the authors present a complete ECVF measurement framework including a
      point-guided myocardial modeling, a deformable model-based myocardium
      segmentation, nonrigid registration of pre- and post-CT, and ECVF calculation.
      RESULTS: The proposed method was evaluated on 20 patients by two observers.
      Compared to the manually delineated reference segmentations, the accuracy of our
      segmentation in terms of true positive volume fraction (TPVF), false positive
      volume fraction (FPVF), and average surface distance (ASD), were 92.18% +/-
      3.52%, 0.31% +/- 0.10%, 0.69 +/- 0.14 mm, respectively. The interobserver
      variability measured by concordance correlation coefficient regarding TPVF, FPVF,
      and ASD were 0.95, 0.90, 0.94, respectively, demonstrating excellent agreement.
      Bland-Altman method showed 95% limits of agreement between ECVF at CT and ECVF at
      MR. CONCLUSIONS: The proposed framework demonstrates its efficiency, accuracy,
      and noninvasiveness in ECVF measurement and dramatically advances the ECVF at
      cardiac CT toward its clinical use.

PMID- 24089935
TI  - Content-based image retrieval of multiphase CT images for focal liver lesion
      characterization.
AB  - PURPOSE: Characterization of focal liver lesions with various imaging modalities
      can be very challenging in the clinical practice and is experience-dependent. The
      authors' aim is to develop an automatic method to facilitate the characterization
      of focal liver lesions (FLLs) using multiphase computed tomography (CT) images by
      radiologists. METHODS: A multiphase-image retrieval system is proposed to
      retrieve a preconstructed database of FLLs with confirmed diagnoses, which can
      assist radiologists' decision-making in FLL characterization. It first localizes
      the FLL on multiphase CT scans using a hybrid generative-discriminative FLL
      detection method and a nonrigid B-spline registration method. Then, it extracts
      the multiphase density and texture features to numerically represent the FLL.
      Next, it compares the query FLL with the model FLLs in the database in terms of
      the feature and measures their similarities using the L1-norm based similarity
      scores. The model FLLs are ranked by similarities and the top results are finally
      provided to the users for their evidence studies. RESULTS: The system was tested
      on a database of 69 four-phase contrast-enhanced CT scans, consisting of six
      classes of liver lesions, and evaluated in terms of the precision-recall curve
      and the Bull's Eye Percentage Score (BEP). It obtained a BEP score of 78%.
      Compared with any single-phase based representation, the multiphase-based
      representation increased the BEP scores of the system, from 63%-65% to 78%. In a
      pilot study, two radiologists performed characterization of FLLs without and with
      the knowledge of the top five retrieved results. The results were evaluated in
      terms of the diagnostic accuracy, the receiver operating characteristic (ROC)
      curve and the mean diagnostic confidence. One radiologist's accuracy improved
      from 75% to 92%, the area under ROC curves (AUC) from 0.85 to 0.95 (p = 0.081),
      and the mean diagnostic confidence from 4.6 to 7.3 (p = 0.039). The second
      radiologist's accuracy did not change, at 75%, with AUC increasing from 0.72 to
      0.75 (p = 0.709), and the mean confidence from 4.5 to 4.9 (p = 0.607).
      CONCLUSIONS: Multiphase CT images can be used in content-based image retrieval
      for FLL's categorization and result in good performance in comparison with single
      phase CT images. The proposed method has the potential to improve the
      radiologists' diagnostic accuracy and confidence by providing visually similar
      lesions with confirmed diagnoses for their interpretation of clinical studies.

PMID- 24089937
TI  - Spatially dependent parameter estimation and nonlinear data assimilation by
      autosynchronization of a system of partial differential equations.
AB  - Given multiple images that describe chaotic reaction-diffusion dynamics,
      parameters of a partial differential equation (PDE) model are estimated using
      autosynchronization, where parameters are controlled by synchronization of the
      model to the observed data. A two-component system of predator-prey reaction
      diffusion PDEs is used with spatially dependent parameters to benchmark the
      methods described. Applications to modeling the ecological habitat of marine
      plankton blooms by nonlinear data assimilation through remote sensing are
      discussed. 

PMID- 24089939
TI  - Predicting the behavior of a chaotic pendulum with a variable interaction
      potential.
AB  - The behavior of a chaotic physical pendulum is significantly modified through the
      addition of a magnetic interaction. The extended behavior is studied through
      identifying distinct characteristics in the Poincare sections and turning point
      maps of the systems. The validity of our model is shown through simulated
      bifurcations generated from coefficients estimated at a number of different
      frequencies. These simulated bifurcations also demonstrate that coefficients
      estimated at one frequency can be used to predict the behavior of the system at a
      different drive frequency. A quantitative measure of the correlation dimension
      shows that the simulated Poincare diagrams are in good agreement with experiment
      and theory. Possible sources of bias in modeled systems are identified. 

PMID- 24089938
TI  - Spatial dynamics in a predator-prey model with herd behavior.
AB  - In this paper, a spatial predator-prey model with herd behavior in prey
      population and quadratic mortality in predator population is investigated. By the
      linear stability analysis, we obtain the condition for stationary pattern.
      Moreover, using standard multiple-scale analysis, we establish the amplitude
      equations for the excited modes, which determine the stability of amplitudes
      towards uniform and inhomogeneous perturbations. By numerical simulations, we
      find that the model exhibits complex pattern replication: spotted pattern, stripe
      pattern, and coexistence of the two. The results may enrich the pattern dynamics
      in predator-prey models and help us to better understand the dynamics of predator
      prey interactions in a real environment. 

PMID- 24089940
TI  - Frustration induced oscillator death on networks.
AB  - An array of identical maps with Ising symmetry, with both positive and negative
      couplings, is studied. We divide the maps into two groups, with positive intra
      group couplings and negative inter-group couplings. This leads to
      antisynchronization between the two groups which have the same stability
      properties as the synchronized state. Introducing a certain degree of randomness
      in signs of these couplings destabilizes the anti-synchronized state. Further
      increasing the randomness in signs of these couplings leads to oscillator death.
      This is essentially a frustration induced phenomenon. We explain the observed
      results using the theory of random matrices with nonzero mean. We briefly discuss
      applications to coupled differential equations. 

PMID- 24089941
TI  - Adaptive coupling optimized spiking coherence and synchronization in Newman-Watts
      neuronal networks.
AB  - In this paper, we have numerically studied the effect of adaptive coupling on the
      temporal coherence and synchronization of spiking activity in Newman-Watts
      Hodgkin-Huxley neuronal networks. It is found that random shortcuts can enhance
      the spiking synchronization more rapidly when the increment speed of adaptive
      coupling is increased and can optimize the temporal coherence of spikes only when
      the increment speed of adaptive coupling is appropriate. It is also found that
      adaptive coupling strength can enhance the synchronization of spikes and can
      optimize the temporal coherence of spikes when random shortcuts are appropriate.
      These results show that adaptive coupling has a big influence on random shortcuts
      related spiking activity and can enhance and optimize the temporal coherence and
      synchronization of spiking activity of the network. These findings can help
      better understand the roles of adaptive coupling for improving the information
      processing and transmission in neural systems. 

PMID- 24089942
TI  - Random walks on non-homogenous weighted Koch networks.
AB  - In this paper, we introduce new models of non-homogenous weighted Koch networks
      on real traffic systems depending on the three scaling factors r1,r2,r3?(0,1).
      Inspired by the definition of the average weighted shortest path (AWSP), we
      define the average weighted receiving time (AWRT). Assuming that the walker, at
      each step, starting from its current node, moves uniformly to any of its
      neighbors, we show that in large network, the AWRT grows as power-law function of
      the network order with the exponent, represented by
      theta(r1,r2,r3)=log4(1+r1+r2+r3). Moreover, the AWSP, in the infinite network
      order limit, only depends on the sum of scaling factors r1,r2,r3. 

PMID- 24089943
TI  - Lagrangian coherent structures at the onset of hyperchaos in the two-dimensional
      Navier-Stokes equations.
AB  - We study a transition to hyperchaos in the two-dimensional incompressible Navier
      Stokes equations with periodic boundary conditions and an external forcing term.
      Bifurcation diagrams are constructed by varying the Reynolds number, and a
      transition to hyperchaos (HC) is identified. Before the onset of HC, there is
      coexistence of two chaotic attractors and a hyperchaotic saddle. After the
      transition to HC, the two chaotic attractors merge with the hyperchaotic saddle,
      generating random switching between chaos and hyperchaos, which is responsible
      for intermittent bursts in the time series of energy and enstrophy. The chaotic
      mixing properties of the flow are characterized by detecting Lagrangian coherent
      structures. After the transition to HC, the flow displays complex Lagrangian
      patterns and an increase in the level of Lagrangian chaoticity during the bursty
      periods that can be predicted statistically by the hyperchaotic saddle prior to
      HC transition. 

PMID- 24089944
TI  - Chen's attractor exists if Lorenz repulsor exists: the Chen system is a special
      case of the Lorenz system.
AB  - In this paper, we show, by means of a linear scaling in time and coordinates,
      that the Chen system, given by x=a(y-x), y=(c-a)x+cy-xz, z=-bz+xy, is,
      generically (c?0), a special case of the Lorenz system. First, we infer that it
      is enough to consider two parameters to study its dynamics. Furthermore, we prove
      that there exists a homothetic transformation between the Chen and the Lorenz
      systems and, accordingly, all the dynamical behavior exhibited by the Chen system
      is present in the Lorenz system (since the former is a special case of the
      second). We illustrate our results relating Hopf bifurcations, periodic orbits,
      invariant surfaces, and chaotic attractors of both systems. Since there has been
      a large literature that has ignored this equivalence, the aim of this paper is to
      review and clarify this field. Unfortunately, a lot of the previous papers on the
      Chen system are unnecessary or incorrect.

PMID- 24089945
TI  - Exactly solvable chaos in an electromechanical oscillator.
AB  - A novel electromechanical chaotic oscillator is described that admits an exact
      analytic solution. The oscillator is a hybrid dynamical system with governing
      equations that include a linear second order ordinary differential equation with
      negative damping and a discrete switching condition that controls the oscillatory
      fixed point. The system produces provably chaotic oscillations with a topological
      structure similar to either the Lorenz butterfly or Rossler's folded-band
      oscillator depending on the configuration. Exact solutions are written as a
      linear convolution of a fixed basis pulse and a sequence of discrete symbols. We
      find close agreement between the exact analytical solutions and the physical
      oscillations. Waveform return maps for both configurations show equivalence to
      either a shift map or tent map, proving the chaotic nature of the oscillations. 

PMID- 24089946
TI  - Detecting chaos in irregularly sampled time series.
AB  - Recently, Wiebe and Virgin [Chaos 22, 013136 (2012)] developed an algorithm which
      detects chaos by analyzing a time series' power spectrum which is computed using
      the Discrete Fourier Transform (DFT). Their algorithm, like other time series
      characterization algorithms, requires that the time series be regularly sampled.
      Real-world data, however, are often irregularly sampled, thus, making the
      detection of chaotic behavior difficult or impossible with those methods. In this
      paper, a characterization algorithm is presented, which effectively detects chaos
      in irregularly sampled time series. The work presented here is a modification of
      Wiebe and Virgin's algorithm and uses the Lomb-Scargle Periodogram (LSP) to
      compute a series' power spectrum instead of the DFT. The DFT is not appropriate
      for irregularly sampled time series. However, the LSP is capable of computing the
      frequency content of irregularly sampled data. Furthermore, a new method of
      analyzing the power spectrum is developed, which can be useful for
      differentiating between chaotic and non-chaotic behavior. The new
      characterization algorithm is successfully applied to irregularly sampled data
      generated by a model as well as data consisting of observations of variable
      stars. 

PMID- 24089947
TI  - A fractal theory based fractional diffusion model used for the fast desorption
      process of methane in coal.
AB  - Based on the realistic property of the pore structure in coal, we established a
      fractal theory based Fractional diffusion model (FFDModel) by introducing the
      fractal dimension df to the Fick's classical model and changing the first-order
      partial differential equation about time into a upsilon fractional-order partial
      differential equation. Then, the solution of the FFDModel was obtained with
      separation variables technique. In order to verify the correctness of the
      solution, three coal samples with different rank from China were collected to do
      the methane desorption experiment of the fast desorption stage. The results
      indicate that the fractal dimension (df) of the coking coal is the lowest of the
      three coal ranks. By comparing the FFDModel with Fick's classical model, we can
      see that the FFDModel fits better with the three measured samples. 

PMID- 24089948
TI  - Theory of intermittency applied to classical pathological cases.
AB  - The classical theory of intermittency developed for return maps assumes uniform
      density of points reinjected from the chaotic to laminar region. Though it works
      fine in some model systems, there exist a number of so-called pathological cases
      characterized by a significant deviation of main characteristics from the values
      predicted on the basis of the uniform distribution. Recently, we reported on how
      the reinjection probability density (RPD) can be generalized. Here, we extend
      this methodology and apply it to different dynamical systems exhibiting anomalous
      type-II and type-III intermittencies. Estimation of the universal RPD is based on
      fitting a linear function to experimental data and requires no a priori knowledge
      on the dynamical model behind. We provide special fitting procedure that enables
      robust estimation of the RPD from relatively short data sets (dozens of points).
      Thus, the method is applicable for a wide variety of data sets including
      numerical simulations and real-life experiments. Estimated RPD enables analytic
      evaluation of the length of the laminar phase of intermittent behaviors. We show
      that the method copes well with dynamical systems exhibiting significantly
      different statistics reported in the literature. We also derive and classify
      characteristic relations between the mean laminar length and main controlling
      parameter in perfect agreement with data provided by numerical simulations. 

PMID- 24089949
TI  - A period-doubling cascade precedes chaos for planar maps.
AB  - A period-doubling cascade is often seen in numerical studies of those smooth (one
      parameter families of) maps for which as the parameter is varied, the map
      transitions from one without chaos to one with chaos. Our emphasis in this paper
      is on establishing the existence of such a cascade for many maps with phase space
      dimension 2. We use continuation methods to show the following: under certain
      general assumptions, if at one parameter there are only finitely many periodic
      orbits, and at another parameter value there is chaos, then between those two
      parameter values there must be a cascade. We investigate only families that are
      generic in the sense that all periodic orbit bifurcations are generic. Our method
      of proof in showing there is one cascade is to show there must be infinitely many
      cascades. We discuss in detail two-dimensional families like those which arise as
      a time-2pi maps for the Duffing equation and the forced damped pendulum equation.

PMID- 24089950
TI  - Pinning controllability of complex networks with community structure.
AB  - In this paper, we study the controllability of networks with different numbers of
      communities and various strengths of community structure. By means of
      simulations, we show that the degree descending pinning scheme performs best
      among several considered pinning schemes under a small number of pinned nodes,
      while the degree ascending pinning scheme is becoming more powerful by increasing
      the number of pinned nodes. It is found that increasing the number of communities
      or reducing the strength of community structure is beneficial for the enhancement
      of the controllability. Moreover, it is revealed that the pinning scheme with
      evenly distributed pinned nodes among communities outperforms other kinds of
      considered pinning schemes. 

PMID- 24089951
TI  - Domain wall and bifurcation analysis of the Klein-Gordon Zakharov equation in
      (1+2)-dimensions with power law nonlinearity.
AB  - This paper studies the Klein-Gordon Zakharov equation with power law nonlinearity
      in (1+2)-dimensions. The ansatz method will be applied to obtain the 1-soliton
      solution, also known as domain wall solution, along with several constraint
      conditions that naturally fall out. Subsequently, the bifurcation analysis is
      carried out where the phase portrait is given. Additionally, this analysis leads
      to several solutions to the equation with the traveling wave scheme. This gives
      soliton solution as well as singular periodic solutions. Finally, the numerical
      simulations for the domain wall solution were obtained where the finite
      difference scheme is applied.

PMID- 24089952
TI  - Phase and amplitude dynamics in large systems of coupled oscillators: growth
      heterogeneity, nonlinear frequency shifts, and cluster states.
AB  - This paper addresses the behavior of large systems of heterogeneous, globally
      coupled oscillators each of which is described by the generic Landau-Stuart
      equation, which incorporates both phase and amplitude dynamics of individual
      oscillators. One goal of our paper is to investigate the effect of a spread in
      the amplitude growth parameter of the oscillators and of the effect of a
      homogeneous nonlinear frequency shift. Both of these effects are of potential
      relevance to recently reported experiments. Our second goal is to gain further
      understanding of the macroscopic system dynamics at large coupling strength, and
      its dependence on the nonlinear frequency shift parameter. It is proven that at
      large coupling strength, if the nonlinear frequency shift parameter is below a
      certain value, then there is a unique attractor for which the oscillators all
      clump at a single amplitude and uniformly rotating phase (we call this a single
      cluster "locked state"). Using a combination of analytical and numerical methods,
      we show that at higher values of the nonlinear frequency shift parameter, the
      single-cluster locked state attractor continues to exist, but other types of
      coexisting attractors emerge. These include two-cluster locked states, periodic
      orbits, chaotic orbits, and quasiperiodic orbits. 

PMID- 24089953
TI  - The unsaturated bistable stochastic resonance system.
AB  - We investigated the characteristics of the output saturation of the classical
      continuous bistable system (saturation bistable system) and its impact on
      stochastic resonance (SR). We further proposed a piecewise bistable SR system
      (unsaturated bistable system) and developed the expression of signal-to-noise
      ratio (SNR) using the adiabatic approximation theory. Compared with the
      saturation bistable system, the SNR is significantly improved in our unsaturated
      bistable SR system. The numerical simulation showed that the unsaturated bistable
      system performed better in extracting weak signals from strong background noise
      than the saturation bistable system. 

PMID- 24089954
TI  - Synchronization of weakly nonlinear oscillators with Huygens' coupling.
AB  - In this paper, the occurrence of synchronization in pairs of weakly nonlinear
      self-sustained oscillators that interact via Huygens' coupling, i.e., a suspended
      rigid bar, is treated. In the analysis, a generalized version of the classical
      Huygens' experiment of synchronization of two coupled pendulum clocks is
      considered, in which the clocks are replaced by arbitrary self-sustained
      oscillators. Sufficient conditions for the existence and stability of synchronous
      solutions in the coupled system are derived by using the Poincare method. The
      obtained results are supported by computer simulations and experiments conducted
      on a dedicated experimental platform. It is demonstrated that the mass of the
      coupling bar is an important parameter with respect to the limit synchronous
      behaviour in the oscillators. 

PMID- 24089955
TI  - Cross-diffusion in the two-variable Oregonator model.
AB  - We explore the effect of cross-diffusion on pattern formation in the two-variable
      Oregonator model of the Belousov-Zhabotinsky reaction. For high negative cross
      diffusion of the activator (the activator being attracted towards regions of
      increased inhibitor concentration) we find, depending on the values of the
      parameters, Turing patterns, standing waves, oscillatory Turing patterns, and
      quasi-standing waves. For the inhibitor, we find that positive cross-diffusion
      (the inhibitor being repelled by increasing concentrations of the activator) can
      induce Turing patterns, jumping waves and spatially modulated bulk oscillations.
      We qualitatively explain the formation of these patterns. With one model we can
      explain Turing patterns, standing waves and jumping waves, which previously was
      done with three different models. 

PMID- 24089956
TI  - Mixed mode and sequential oscillations in the cerium-bromate-4-aminophenol
      photoreaction.
AB  - Cerium was introduced to the bromate-aminophenol photochemical oscillator to
      implement coupled autocatalytic feedbacks. Mixed mode and sequential oscillations
      emerged in the studied system, making it one of the few chemical oscillators
      known to support consecutive bifurcations in a batch system. The complex reaction
      behavior showed a strong dependence on the intensity of illumination supplied to
      the system. Removal of illumination during an oscillatory window affected both
      the frequency and amplitude of the oscillation but did not fully extinguish them,
      indicating that the cerium-bromate-4-aminophenol oscillator was photosensitive
      rather than photo-controlled. A moderate light intensity allowed for a slow
      evolution of the system, which proved to be critical for the emergence of
      transient complex oscillations. Variation of individual reaction parameters was
      carried out, which indicated that the development of complex oscillations occur
      in a narrow region and a phase diagram in the 4-aminophenol and sulfuric acid
      plane demonstrated this. Simulations provide strong support that transient
      complex oscillations observed experimentally arise from the coupling of two
      autocatalytic cycles. 

PMID- 24089957
TI  - Impact of delays on the synchronization transitions of modular neuronal networks
      with hybrid synapses.
AB  - The combined effects of the information transmission delay and the ratio of the
      electrical and chemical synapses on the synchronization transitions in the hybrid
      modular neuronal network are investigated in this paper. Numerical results show
      that the synchronization of neuron activities can be either promoted or destroyed
      as the information transmission delay increases, irrespective of the probability
      of electrical synapses in the hybrid-synaptic network. Interestingly, when the
      number of the electrical synapses exceeds a certain level, further increasing its
      proportion can obviously enhance the spatiotemporal synchronization transitions.
      Moreover, the coupling strength has a significant effect on the synchronization
      transition. The dominated type of the synapse always has a more profound effect
      on the emergency of the synchronous behaviors. Furthermore, the results of the
      modular neuronal network structures demonstrate that excessive partitioning of
      the modular network may result in the dramatic detriment of neuronal
      synchronization. Considering that information transmission delays are inevitable
      in intra- and inter-neuronal networks communication, the obtained results may
      have important implications for the exploration of the synchronization mechanism
      underlying several neural system diseases such as Parkinson's Disease. 

PMID- 24089958
TI  - Synchrony suppression in ensembles of coupled oscillators via adaptive vanishing
      feedback.
AB  - Synchronization and emergence of a collective mode is a general phenomenon,
      frequently observed in ensembles of coupled self-sustained oscillators of various
      natures. In several circumstances, in particular in cases of neurological
      pathologies, this state of the active medium is undesirable. Destruction of this
      state by a specially designed stimulation is a challenge of high clinical
      relevance. Typically, the precise effect of an external action on the ensemble is
      unknown, since the microscopic description of the oscillators and their
      interactions are not available. We show that, desynchronization in case of a
      large degree of uncertainty about important features of the system is
      nevertheless possible; it can be achieved by virtue of a feedback loop with an
      additional adaptation of parameters. The adaptation also ensures
      desynchronization of ensembles with non-stationary, time-varying parameters. We
      perform the stability analysis of the feedback-controlled system and demonstrate
      efficient destruction of synchrony for several models, including those of spiking
      and bursting neurons. 

PMID- 24089959
TI  - Chaos and noise.
AB  - Simple dynamical systems--with a small number of degrees of freedom--can behave
      in a complex manner due to the presence of chaos. Such systems are most often
      (idealized) limiting cases of more realistic situations. Isolating a small number
      of dynamical degrees of freedom in a realistically coupled system generically
      yields reduced equations with terms that can have a stochastic interpretation. In
      situations where both noise and chaos can potentially exist, it is not
      immediately obvious how Lyapunov exponents, key to characterizing chaos, should
      be properly defined. In this paper, we show how to do this in a class of well
      defined noise-driven dynamical systems, derived from an underlying Hamiltonian
      model.

PMID- 24089960
TI  - Explosive synchronization transitions in complex neural networks.
AB  - It has been recently reported that explosive synchronization transitions can take
      place in networks of phase oscillators [Gomez-Gardenes et al. Phys. Rev. Lett.
      106, 128701 (2011)] and chaotic oscillators [Leyva et al. Phys. Rev. Lett. 108,
      168702 (2012)]. Here, we investigate the effect of a microscopic correlation
      between the dynamics and the interacting topology of coupled FitzHugh-Nagumo
      oscillators on phase synchronization transition in Barabasi-Albert (BA) scale
      free networks and Erdos-Renyi (ER) random networks. We show that, if natural
      frequencies of the oscillations are positively correlated with node degrees and
      the width of the frequency distribution is larger than a threshold value, a
      strong hysteresis loop arises in the synchronization diagram of BA networks,
      indicating the evidence of an explosive transition towards synchronization of
      relaxation oscillators system. In contrast to the results in BA networks, in more
      homogeneous ER networks, the synchronization transition is always of continuous
      type regardless of the width of the frequency distribution. Moreover, we consider
      the effect of degree-mixing patterns on the nature of the synchronization
      transition, and find that the degree assortativity is unfavorable for the
      occurrence of such an explosive transition. 

PMID- 24089961
TI  - Deterministic and stochastic bifurcations in the Hindmarsh-Rose neuronal model.
AB  - We analyze the bifurcations occurring in the 3D Hindmarsh-Rose neuronal model
      with and without random signal. When under a sufficient stimulus, the neuron
      activity takes place; we observe various types of bifurcations that lead to
      chaotic transitions. Beside the equilibrium solutions and their stability, we
      also investigate the deterministic bifurcation. It appears that the neuronal
      activity consists of chaotic transitions between two periodic phases called
      bursting and spiking solutions. The stochastic bifurcation, defined as a sudden
      change in character of a stochastic attractor when the bifurcation parameter of
      the system passes through a critical value, or under certain condition as the
      collision of a stochastic attractor with a stochastic saddle, occurs when a
      random Gaussian signal is added. Our study reveals two kinds of stochastic
      bifurcation: the phenomenological bifurcation (P-bifurcations) and the dynamical
      bifurcation (D-bifurcations). The asymptotical method is used to analyze
      phenomenological bifurcation. We find that the neuronal activity of spiking and
      bursting chaos remains for finite values of the noise intensity. 

PMID- 24089962
TI  - Phase locking route behind complex periodic windows in a forced oscillator.
AB  - Chaotic systems have complex reactions against an external driving force; even in
      cases with low-dimension oscillators, the routes to synchronization are diverse.
      We proposed a stroboscope-based method for analyzing driven chaotic systems in
      their phase space. According to two statistic quantities generated from time
      series, we could realize the system state and the driving behavior
      simultaneously. We demonstrated our method in a driven bi-stable system, which
      showed complex period windows under a proper driving force. With increasing
      periodic driving force, a route from interior periodic oscillation to phase
      synchronization through the chaos state could be found. Periodic windows could
      also be identified and the circumstances under which they occurred distinguished.
      Statistical results were supported by conditional Lyapunov exponent analysis to
      show the power in analyzing the unknown time series. 

PMID- 24089963
TI  - Universal fractional map and cascade of bifurcations type attractors.
AB  - We modified the way in which the Universal Map is obtained in the regular
      dynamics to derive the Universal alpha-Family of Maps depending on a single
      parameter alpha>0, which is the order of the fractional derivative in the
      nonlinear fractional differential equation describing a system experiencing
      periodic kicks. We consider two particular alpha-families corresponding to the
      Standard and Logistic Maps. For fractional alpha<2 in the area of parameter
      values of the transition through the period doubling cascade of bifurcations from
      regular to chaotic motion in regular dynamics corresponding fractional systems
      demonstrate a new type of attractors--cascade of bifurcations type trajectories.

PMID- 24089964
TI  - Modulated pressure waves in large elastic tubes.
AB  - Modulational instability is the direct way for the emergence of wave patterns and
      localized structures in nonlinear systems. We show in this work that it can be
      explored in the framework of blood flow models. The whole modified Navier-Stokes
      equations are reduced to a difference-differential amplitude equation. The
      modulational instability criterion is therefore derived from the latter, and
      unstable patterns occurrence is discussed on the basis of the nonlinear parameter
      model of the vessel. It is found that the critical amplitude is an increasing
      function of alpha, whereas the region of instability expands. The subsequent
      modulated pressure waves are obtained through numerical simulations, in agreement
      with our analytical expectations. Different classes of modulated pressure waves
      are obtained, and their close relationship with Mayer waves is discussed. 

PMID- 24089965
TI  - Intermittency of intermittencies.
AB  - A phenomenon of intermittency of intermittencies is discovered in the temporal
      behavior of two coupled complex systems. We observe for the first time the
      coexistence of two types of intermittent behavior taking place simultaneously
      near the boundary of the synchronization regime of coupled chaotic oscillators.
      This phenomenon is found both in the numerical and physiological experiments. The
      laws for both the distribution and mean length of laminar phases versus the
      control parameter values are analytically deduced. A very good agreement between
      the theoretical results and simulation is shown. 

PMID- 24089966
TI  - Reversal of spiral waves in an oscillatory system caused by an inhomogeneity.
AB  - Spatial heterogeneities are commonly found in realistic systems and play
      significant roles in dynamics of spiral waves. We here demonstrate a novel
      phenomenon that a localized inhomogeneity put around the spiral core could lead
      to the reversal of spiral waves in an oscillatory system, e.g., the complex
      Ginzburg-Landau equation. With the amplitude-phase representation, we analyze
      underling mechanism and conditions of the wave reversal in detail, which is found
      to agree with the numerical evidence. 

PMID- 24089967
TI  - Eigenvector centrality of nodes in multiplex networks.
AB  - We extend the concept of eigenvector centrality to multiplex networks, and
      introduce several alternative parameters that quantify the importance of nodes in
      a multi-layered networked system, including the definition of vectorial-type
      centralities. In addition, we rigorously show that, under reasonable conditions,
      such centrality measures exist and are unique. Computer experiments and
      simulations demonstrate that the proposed measures provide substantially
      different results when applied to the same multiplex structure, and highlight the
      non-trivial relationships between the different measures of centrality
      introduced. 

PMID- 24089968
TI  - Series-NonUniform Rational B-Spline (S-NURBS) model: a geometrical interpolation
      framework for chaotic data.
AB  - Time series is widely exploited to study the innate character of the complex
      chaotic system. Existing chaotic models are weak in modeling accuracy because of
      adopting either error minimization strategy or an acceptable error to end the
      modeling process. Instead, interpolation can be very useful for solving
      differential equations with a small modeling error, but it is also very difficult
      to deal with arbitrary-dimensional series. In this paper, geometric theory is
      considered to reduce the modeling error, and a high-precision framework called
      Series-NonUniform Rational B-Spline (S-NURBS) model is developed to deal with
      arbitrary-dimensional series. The capability of the interpolation framework is
      proved in the validation part. Besides, we verify its reliability by
      interpolating Musa dataset. The main improvement of the proposed framework is
      that we are able to reduce the interpolation error by properly adjusting weights
      series step by step if more information is given. Meanwhile, these experiments
      also demonstrate that studying the physical system from a geometric perspective
      is feasible. 

PMID- 24089969
TI  - A dynamical systems approach to the control of chaotic dynamics in a
      spatiotemporal jet flow.
AB  - We present a strategy for control of chaos in open flows and provide its
      experimental validation in the near field of a transitional jet flow system. The
      low-dimensional chaotic dynamics studied here results from vortex ring formation
      and their pairings over a spatially extended region of the flow that was excited
      by low level periodic forcing of the primary instability. The control method
      utilizes unstable periodic orbits (UPO) embedded within the chaotic attractor.
      Since hydrodynamic instabilities in the open flow system are convective, both
      monitoring and control can be implemented at a few locations, resulting in a
      simple and effective control algorithm. Experiments were performed in an
      incompressible, initially laminar, 4 cm diameter circular air jet, at a Reynolds
      number of 23,000, housed in a low-noise, large anechoic chamber. Distinct
      trajectory bundles surrounding the dominant UPOs were found from experimentally
      derived, time-delayed embedding of the chaotic attractor. Velocity traces from a
      pair of probes placed at the jet flow exit and farther downstream were used to
      empirically model the UPOs and compute control perturbations to be applied at the
      jet nozzle lip. Open loop control was used to sustain several nearly periodic
      states.

PMID- 24089970
TI  - A framework for estimating potential fluid flow from digital imagery.
AB  - Given image data of a fluid flow, the flow field, <u,v>, governing the evolution
      of the system can be estimated using a variational approach to optical flow.
      Assuming that the flow field governing the advection is the symplectic gradient
      of a stream function or the gradient of a potential function-both falling under
      the category of a potential flow-it is natural to re-frame the optical flow
      problem to reconstruct the stream or potential function directly rather than the
      components of the flow individually. There are several advantages to this
      framework. Minimizing a functional based on the stream or potential function
      rather than based on the components of the flow will ensure that the computed
      flow is a potential flow. Next, this approach allows a more natural method for
      imposing scientific priors on the computed flow, via regularization of the
      optical flow functional. Also, this paradigm shift gives a framework--rather than
      an algorithm--and can be applied to nearly any existing variational optical flow
      technique. In this work, we develop the mathematical formulation of the potential
      optical flow framework and demonstrate the technique on synthetic flows that
      represent important dynamics for mass transport in fluid flows, as well as a flow
      generated by a satellite data-verified ocean model of temperature transport.

PMID- 24089971
TI  - An efficient approach to suppress the negative role of contrarian oscillators in
      synchronization.
AB  - It has been found that contrarian oscillators usually take a negative role in the
      collective behaviors formed by conformist oscillators. However, experiments
      revealed that it is also possible to achieve a strong coherence even when there
      are contrarians in the system such as neuron networks with both excitable and
      inhibitory neurons. To understand the underlying mechanism of this abnormal
      phenomenon, we here consider a complex network of coupled Kuramoto oscillators
      with mixed positive and negative couplings and present an efficient approach,
      i.e., tit-for-tat strategy, to suppress the negative role of contrarian
      oscillators in synchronization and thus increase the order parameter of
      synchronization. Two classes of contrarian oscillators are numerically studied
      and a brief theoretical analysis is provided to explain the numerical results. 

PMID- 24089972
TI  - Identifying homoclinic orbits in the dynamics of intermittent signals through
      recurrence quantification.
AB  - In this paper, we show how the phenomenon of intermittency observed in systems
      with turbulent flow-sound interaction is related to the formation of homoclinic
      orbits in the phase space. Such orbits that emerge via the intersection of the
      stable and unstable manifold of an equilibrium configuration result from
      interactions that happen at multiple spatial/temporal scales associated with
      turbulent convection and wave propagation. Through a quantification of the time
      spent by the dynamics in the aperiodic states using recurrence plots, we show how
      the presence of homoclinic orbits in the dynamics may be convincingly
      demonstrated, which is often not possible through a visual inspection of the
      phase space of the attractor. 

PMID- 24089973
TI  - Soliton behavior for a generalized mixed nonlinear Schrodinger model with N-fold
      Darboux transformation.
AB  - A spectral problem, the x-derivative part of which is a simple generalization of
      the standard Ablowitz-Kaup-Newell-Segur and Kaup-Newell spectral problems, is
      presented with its associated generalized mixed nonlinear Schrodinger (GMNLS)
      model. The N-fold Darboux transformation with multi-parameters for the spectral
      problem is constructed with the help of gauge transformation. According to the
      Darboux transformation, the solution of the GMNLS model is reduced to solving a
      linear algebraic system and two first-order ordinary differential equations. As
      an example of application, we list the modulus formulae of the envelope one- and
      two-soliton solutions. Note that our model is a generalized one with the
      inclusion of four coefficients (a, b, c, and d), which involves abundant NLS-type
      models such as the standard cubic NLS equation, the Gerdjikov-Ivanov equation,
      the Chen-Lee-Liu equation, the Kaup-Newell equation, and the mixed NLS of Wadati
      and/or Kundu, among others. 

PMID- 24089974
TI  - Transition to almost periodic patterns in circle map with delay: persistence as
      order parameter.
AB  - We study delayed circle map. A previously proposed analogy between delayed map
      and spatiotemporal system [F. T. Arecchi et al., Phys. Rev. A 45, R4225 (1992)]
      is employed to study this system. In the phase diagram, we observe laminar phase,
      travelling defect phase, and standing defect phase. We push this analogy further;
      and in this pseudo-spatiotemporal system, we investigate "phases" and define
      "order parameter" to describe transition between phases. We find that persistence
      (defined as the probability that a given site has not deviated even once from its
      coarse grained initial state upto time t) works as an "order parameter" for the
      transition from a travelling wave phase to standing wave phase. We observe an
      interesting finite "size" scaling and off-critical scaling above the critical
      point. 

PMID- 24089975
TI  - Assortative mixing in functional brain networks during epileptic seizures.
AB  - We investigate assortativity of functional brain networks before, during, and
      after one-hundred epileptic seizures with different anatomical onset locations.
      We construct binary functional networks from multi-channel
      electroencephalographic data recorded from 60 epilepsy patients; and from time
      resolved estimates of the assortativity coefficient, we conclude that positive
      degree-degree correlations are inherent to seizure dynamics. While seizures
      evolve, an increasing assortativity indicates a segregation of the underlying
      functional network into groups of brain regions that are only sparsely
      interconnected, if at all. Interestingly, assortativity decreases already prior
      to seizure end. Together with previous observations of characteristic temporal
      evolutions of global statistical properties and synchronizability of epileptic
      brain networks, our findings may help to gain deeper insights into the
      complicated dynamics underlying generation, propagation, and termination of
      seizures. 

PMID- 24089976
TI  - Time delay induced different synchronization patterns in repulsively coupled
      chaotic oscillators.
AB  - Time delayed coupling plays a crucial role in determining the system's dynamics.
      We here report that the time delay induces transition from the asynchronous state
      to the complete synchronization (CS) state in the repulsively coupled chaotic
      oscillators. In particular, by changing the coupling strength or time delay,
      various types of synchronous patterns, including CS, antiphase CS, antiphase
      synchronization (ANS), and phase synchronization, can be generated. In the
      transition regions between different synchronous patterns, bistable synchronous
      oscillators can be observed. Furthermore, we show that the time-delay-induced
      phase flip bifurcation is of key importance for the emergence of CS. All these
      findings may light on our understanding of neuronal synchronization and
      information processing in the brain. 

PMID- 24089977
TI  - Emitting waves from heterogeneity by a rotating electric field.
AB  - In a generic model of excitable media, we simulate wave emission from a
      heterogeneity (WEH) induced by an electric field. Based on the WEH effect, a
      rotating electric field is proposed to terminate existed spatiotemporal
      turbulence. Compared with the effects resulted by a periodic pulsed electric
      field, the rotating electric field displays several improvements, such as lower
      required intensity, emitting waves on smaller obstacles, and shorter suppression
      time. Furthermore, due to rotation of the electric field, it can automatically
      source waves from the boundary of an obstacle with small curvature. 

PMID- 24089978
TI  - Dynamics in hybrid complex systems of switches and oscillators.
AB  - While considerable progress has been made in the analysis of large systems
      containing a single type of coupled dynamical component (e.g., coupled
      oscillators or coupled switches), systems containing diverse components (e.g.,
      both oscillators and switches) have received much less attention. We analyze
      large, hybrid systems of interconnected Kuramoto oscillators and Hopfield
      switches with positive feedback. In this system, oscillator synchronization
      promotes switches to turn on. In turn, when switches turn on, they enhance the
      synchrony of the oscillators to which they are coupled. Depending on the choice
      of parameters, we find theoretically coexisting stable solutions with either (i)
      incoherent oscillators and all switches permanently off, (ii) synchronized
      oscillators and all switches permanently on, or (iii) synchronized oscillators
      and switches that periodically alternate between the on and off states. Numerical
      experiments confirm these predictions. We discuss how transitions between these
      steady state solutions can be onset deterministically through dynamic
      bifurcations or spontaneously due to finite-size fluctuations. 

PMID- 24089979
TI  - Finite time control of a class of time-varying unified chaotic systems.
AB  - This paper considers the problem of finite time control for a class of time
      varying unified chaotic system. First, based on the finite-time stability theory,
      a novel adaptive control technique is presented to achieve finite-time
      stabilization for time-varying unified chaotic system. Comparing with the
      existing methods, the proposed controller only need to be added on one state
      variable of systems and it is easy to be implemented. Then, a finite time control
      technique is provided to realize the tracking of any target function with second
      order derivatives. Finally, Simulation results are provided to show the
      effectiveness of the proposed method. 

PMID- 24089980
TI  - It is time for "green dialysis".

PMID- 24089981
TI  - DisabilityCare Australia making a difference.

PMID- 24089982
TI  - Job satisfaction, burnout and turnover intention in occupational therapists
      working in mental health.
AB  - BACKGROUND/AIM: Employee wellbeing is an important issue for mental health
      services. Poor employee wellbeing (i.e., high levels of burnout or low job
      satisfaction) is associated with poorer consumer outcomes and higher staff
      turnover. This study set out to examine factors related to job satisfaction,
      turnover intention and burnout in a group of occupational therapists in mental
      health. METHOD: Thirty-four occupational therapists (response rate approximately
      60%) in a metropolitan public mental health service participated in a whole-of
      service workforce survey. The survey included measures of job satisfaction,
      turnover intention, burnout, job hindrances, job challenges and job resources and
      questions about positive and negative aspects of positions and factors that
      attracted employees to their current position. RESULTS: Burnout was associated
      with lower job satisfaction and higher turnover intention. Higher job
      satisfaction was associated with rewards (remuneration and recognition) as well
      as cognitively challenging work. The variables most significantly associated with
      poorer wellbeing (higher turnover intention and burnout) were recipient contact
      demands (perception that contact with service users or families was demanding),
      and feelings of stress or fatigue. CONCLUSION: This study provides a detailed
      analysis of factors associated with job satisfaction, turnover intention and
      burnout in a group of occupational therapists working in mental health. To
      promote workforce wellbeing and enhanced retention, interventions to minimise
      burnout should be implemented and evaluated. These strategies should focus on
      enhancing job resources such as supervisor support, feedback and participation in
      decision making as well as building the personal resilience of occupational
      therapists working in mental health.

PMID- 24089983
TI  - Facilitating early activities of daily living retraining to prevent functional
      decline in older adults.
AB  - BACKGROUND/AIM: Older people admitted to acute hospitals are at risk of
      functional decline. There is limited research into strategies that reduce such
      risks. The aim of this study was to investigate whether individualised activities
      of daily living retraining programmes improve functional outcomes, influence the
      choice of discharge destinations and reduce length of stay for older people in
      acute care. METHODS: A pilot non-randomised controlled study (pre-test/post-test)
      with block allocation to control and intervention groups was undertaken in an
      acute geriatric unit at a large teaching hospital. The study was conducted over a
      six-month period in two consecutive blocks. The intervention group received
      activities of daily living retraining three times per week for up to one hour per
      session. The control group received standard, mainly assessment-based
      occupational therapy services. The Modified Barthel Index was used to measure
      functional status on admission and discharge. RESULTS: At discharge, there was no
      statistical difference in the change of total Modified Barthel Index score
      between control and intervention groups. Of the 10 items scored on the Modified
      Barthel Index, ambulation and chair/bed transfers approached significance (P =
      0.0603 and P = 0.0547 respectively). No evidence was found for a difference in
      length of stay between intervention and control groups (mean length of stay 15.2
      vs. 11.7 days respectively, P = 0.19). Raw data suggested that retraining
      programmes may reduce the level of care patients required on discharge.
      CONCLUSIONS: Trends from this study indicate that functional retraining
      programmes could be effective in preventing functional decline. Further research
      is needed to reach more definite conclusions.

PMID- 24089984
TI  - Working alliance development in occupational therapy: a cross-case analysis.
AB  - BACKGROUND: Despite reverence afforded the therapeutic relationship construct in
      occupational therapy, many occupational therapists feel ill equipped to use
      themselves therapeutically to enhance the relationship with their clients.
      Furthermore, although occupational therapists often link the strength of the
      therapeutic relationship to therapy outcomes, related occupational therapy
      specific research has been limited. According to the psychotherapy literature,
      the working alliance is one element of the therapeutic relationship which has in
      fact been linked to therapy outcomes. METHODS: A mixed-methods, prospective,
      multiple case study approach was used to compare the experiences of the working
      alliance by both occupational therapists and clients across four therapeutic
      dyads. RESULTS: Several key elements were identified in this study's qualitative
      data as shaping the process of alliance development in occupational therapy
      including: the fostering of an interpersonal connection; the use of humour as
      therapeutic modality; an impetus to act that leads to functional enhancements; a
      shared sense of success and a positive feedback mechanism created through
      successfully attaining clearly delineated, client-centred therapy goals.
      CONCLUSIONS: By considering these identified elements, occupational therapists
      may focus upon tangible considerations towards enhanced therapeutic use-of-self
      in the development of sound working alliance with their clients potentially
      improving therapy outcomes.

PMID- 24089985
TI  - Cognitive assessment across the continuum of care: the importance of occupational
      performance-based assessment for individuals post-stroke and traumatic brain
      injury.
AB  - BACKGROUND/AIM: When working with individuals following stroke or traumatic brain
      injury, an important role of the occupational therapist is to assess the impact
      of cognitive impairment on their ability to engage in occupations and resume
      important life roles. The aim of this study was to survey therapists' reasons for
      selection of and challenges with using various cognitive assessment approaches,
      across the continuum of care, when working with individuals following stroke and
      traumatic brain injury. METHODS: A cross-sectional survey, completed via post or
      online, with responses from 209 Australian occupational therapists was conducted.
      Participants included clinicians working in acute, inpatient rehabilitation and
      community settings. RESULTS: Occupational performance-based assessments were
      ranked as the most important assessment method, with 69% of participants
      reporting using these assessments for more than 75% of their clients with
      cognitive impairment. Participants identified the lack of quantitative data
      provided by these assessments as a frequent challenge. The identification of
      cognitive deficits was the highest ranked reason for using cognitive screens and
      batteries. Challenges identified with using cognitive screens and batteries
      included difficulty linking assessment results to occupational performance, and
      difficulty using results to generate intervention strategies. The majority of
      participants reported using a combined approach to assessment, and used screens
      and batteries to support findings of occupational performance-based assessments.
      CONCLUSIONS: Targeted efforts to further incorporate standardised occupational
      performance-based methods into clinical practice, research, and ongoing
      professional development is required to enhance occupational therapy services
      when working with individuals with cognitive impairment.

PMID- 24089986
TI  - Predictors of time to complete toileting for children with spina bifida.
AB  - BACKGROUND/AIM: Previous research has shown that children with spina bifida use
      clean intermittent catheterisation for urination, a rather complex procedure that
      increases the time taken to completion. However, no studies have analysed the
      factors impacting on the time taken to complete the urination that could inform
      occupational therapy practice. Therefore, the aim was to identify the variables
      that predict extended time children with spina bifida take to complete urination.
      METHODS: Fifty children, aged 5-18 years old with spina bifida using clean
      intermittent catheterisation, were observed while toileting and responding to a
      set of assessments tools, among them the Canadian Occupational Performance
      Measure. A logistic regression was used to identify which variables were
      independently associated with an extended toileting time. RESULTS: Children with
      spina bifida do take long time to urinate. More than half of this study's
      participants required more than five minutes completing urination, but not all
      required extended times. Ambulant, independent girls were more likely to perform
      toileting in less than six minutes compared with other children with spina
      bifida. However, age, IQ, maintained focus on the task, Canadian Occupational
      Performance Measure, time processing abilities and self-reported ratings of
      independence appeared to be of no relevance, to predict extended toileting times.
      CONCLUSION: To minimise occupational disruption caused by extended toileting
      times, occupational therapists should utilise the relevant predictors: gender,
      independence and ambulation when they prioritise children for relevant
      interventions.

PMID- 24089987
TI  - Is a computer-based measurement method superior to a recommended manual method by
      the ROHO((r)) Group to assess pressure in the sitting position?
AB  - BACKGROUND: In clinical practice, a manual-based assessment is standard procedure
      to adjust the air pressure in the ROHO((r)) cushion in seated position. Recently,
      a computerized pressure system method was developed to support the clinical
      adjustment of air in the ROHO((r)) cushion to reduce the pressure in the seated
      position. To our knowledge, no studies have investigated the reliability between
      the manual method mostly used in clinical practice and the alternative computer
      based assessment of the pressure in the seated position. AIM: The objective was
      to test intra-tester and inter-tester reliability and evaluate if a computer
      based measurement method is superior to a manual method to reduce pressure in the
      seated position. The cushion used was a Roho Quadtro select((r)) high profile.
      METHODS: An intra-tester and inter-tester reliability study was conducted in 2010
      at the Department of Occupational Therapy and Physiotherapy, Aalborg Hospital,
      Aarhus University Hospital, Denmark. Subjects included were two occupational
      therapists and 20 healthy subjects. The outcome measures were obtained using a
      pressure imaging system that could register pressure distribution in the sitting
      area. RESULTS: The study did not show high intra-class correlation coefficients
      neither in the intra-tester nor in the inter-tester reliability for manual or
      computer-based methods in reducing pressure in the seating position. CONCLUSIONS:
      The current company-recommended air pressure adjustment procedure seems
      unreliable. The technical superiority of the computer-based method over the
      manual method has not been established.

PMID- 24089988
TI  - Occupational therapy and obesity: an integrative literature review.
AB  - BACKGROUND/AIM: Obesity is a significant public health concern globally. It is
      associated with poor physical health, mental health and subjective well-being and
      limitations on occupational participation. With its focus on the relationship
      between occupation, health and well-being, occupational therapy would appear to
      be well placed to address both the causes and consequences of obesity. The aim of
      this review was to explore the scope of the role of occupational therapy practice
      in this field and the supporting evidence base. METHODS: Searches were conducted
      in four online databases and nine occupational therapy journals. Articles were
      included if they were theoretical, quantitative or qualitative research,
      explicitly related to occupational therapy and obesity, published in peer
      reviewed journals, in English between 2002 and 2012. All research articles were
      critically reviewed and thematic analysis was conducted across all of the
      articles in the review. RESULTS: Eight theoretical articles, 12 quantitative and
      two qualitative research studies were included. Only three were outcome studies.
      Thematic analysis identified four categories of focus of occupational therapy
      intervention: health promotion and prevention, increasing physical activity
      participation, modifying dietary intake and reducing the impact of obesity. Four
      categories of intervention strategies were also identified; assessment, modifying
      the environment, education and introducing and adapting occupations. CONCLUSION
      AND SIGNIFICANCE: The findings of this review suggest a comprehensive role for
      occupational therapy in addressing obesity. However, the paucity of outcome
      studies mean that significantly more research is required to further define and
      provide a strong evidence base for occupational therapy practice in this emerging
      field.

PMID- 24089989
TI  - Respecting the evidence: responsible assessment and effective intervention for
      children with handwriting difficulties.

PMID- 24089990
TI  - Establishing a role for occupational therapists in end-of-life care in Western
      Australia.

PMID- 24089991
TI  - Effectiveness of pre-discharge occupational therapy home visits has yet to be
      evaluated; a definitive trial is feasible and warranted.

PMID- 24089992
TI  - Discharge planning reduces length of stay and re-admission rates for older people
      admitted with a medical condition.

PMID- 24089993
TI  - Antiviral activities of Indonesian medicinal plants in the East Java region
      against hepatitis C virus.
AB  - BACKGROUND: Hepatitis C virus (HCV) is a major cause of liver disease and a
      potential cause of substantial morbidity and mortality worldwide. The overall
      prevalence of HCV infection is 2%, representing 120 million people worldwide.
      Current standard treatment using pegylated interferon and ribavirin is effective
      in only 50% of the patients infected with HCV genotype 1, and is associated with
      significant side effects. Therefore, it is still of importance to develop new
      drugs for treatment of HCV. Antiviral substances obtained from natural products,
      including medicinal plants, are potentially good targets to study. In this study,
      we evaluated Indonesian medicinal plants for their anti-HCV activities. METHODS:
      Ethanol extracts of 21 samples derived from 17 species of medicinal plants
      explored in the East Java region were tested. Anti-HCV activities were determined
      by a cell culture method using Huh7.5 cells and HCV strains of 9 different
      genotypes (1a to 7a, 1b and 2b). RESULTS: Four of the 21 samples tested showed
      antiviral activities against HCV: Toona sureni leaves (TSL) with 50% inhibitory
      concentrations (IC50) of 13.9 and 2.0 MUg/ml against the HCV J6/JFH1-P47 and -P1
      strains, respectively, Melicope latifolia leaves (MLL) with IC50 of 3.5 and 2.1
      MUg/ml, respectively, Melanolepis multiglandulosa stem (MMS) with IC50 of 17.1
      and 6.2 MUg/ml, respectively, and Ficus fistulosa leaves (FFL) with IC50 of 15.0
      and 5.7 MUg/ml, respectively. Time-of-addition experiments revealed that TSL and
      MLL inhibited both at the entry and post-entry steps while MMS and FFL
      principally at the entry step. TSL and MLL inhibited all of 11 HCV strains of all
      the genotypes tested to the same extent. On the other hand, FFL showed
      significantly weaker inhibitory activities against the HCV genotype 1a strain,
      and MMS against the HCV strains of genotypes 2b and 7a to a lesser extent,
      compared to the other HCV genotypes. CONCLUSIONS: Ethanol extracts of TSL, MLL,
      MMS and FFL showed antiviral activities against all the HCV genotypes tested with
      the exception that some genotype(s) showed significant resistance to FFL and to
      MMS to a lesser extent. These plant extracts may be good candidates for the
      development of anti-HCV drugs.

PMID- 24089994
TI  - HLA-G is differentially expressed in thyroid tissues.
AB  - BACKGROUND: HLA-G is a nonclassical major histocompatibility complex molecule
      that has well-recognized immunomodulatory properties. The expression of HLA-G in
      tumor cells has been considered to be detrimental, permitting tumor spreading and
      decreased survival. We evaluated the expression of HLA-G in histologically normal
      thyroid tissue, goiter, and benign and malignant thyroid tumors, and studied the
      relationship between HLA-G expression and patient clinical variables. PATIENTS
      AND METHODS: The immunohistochemistry expression of HLA-G was performed on 72
      specimens of papillary thyroid carcinoma (PTC), 19 follicular thyroid carcinomas
      (FTC), 22 follicular adenomas (FA), 22 colloid goiters (CG), and 14
      histologically normal thyroid glands (NT). The percentage of HLA-G staining was
      graded from absent (-) to intense (+++). RESULTS: HLA-G was faintly expressed in
      areas of hyperplasia in NT and CG. In PTC, FTC, and FA, the percentage of cell
      staining was significantly higher than in NT and CG (p<0.001 for each
      comparison). The tumor area with HLA-G expression was greater in FTC (p=0.0059)
      and PTC (p=0.0330) compared to FA. According to the magnitude of HLA-G staining,
      PTC tumors >1 cm exhibited increased HLA-G staining when compared to smaller
      tumors (p=0.03). Aggressive histologic subtypes of PTC have a higher median
      stained tumor area. No association was found between HLA-G expression and tumoral
      staging or patient disease-free survival. CONCLUSIONS: The gradual increase of
      HLA-G expression from hyperplasia to carcinomas, and the association of strong
      HLA staining with some variables implicated in poor prognosis corroborate the
      unfavorable role of HLA-G in tumor thyroid cells, inhibiting cytotoxic immune
      system cells and facilitating tumor evasion and progression.

PMID- 24089995
TI  - Diagnostic use of dermatomal somatosensory-evoked potentials in spinal disorders:
      Case series.
AB  - OBJECTIVE/CONTEXT: Dermatomal somatosensory-evoked potentials (dSEPs) may be
      valuable for diagnostic purposes in selected cases with spinal disorders. DESIGN:
      Reports on cases with successful use of dSEPs. FINDINGS: Cases 1 and 2 had
      lesions causing multiple root involvement (upper to middle lumbar region in Case
      1 and lower sacral region in Case 2). Cystic lesions in both cases seemed to
      compress more than one nerve root, and stimulation at the center of the involved
      dermatomes in dSEPs helped to reveal the functional abnormality. Cases 3 and 4
      had lesions involving the spinal cord with or without nerve root impairment. In
      Case 3, an magnetic resonance imaging (MRI)-verified lesion seemed to occupy a
      considerable volume of the lower spinal cord, causing only very restricted
      clinical sensory and motor signs. In Case 4, a cervical MRI showed a small well
      circumscribed intramedullary lesion at right C2 level. All neurophysiological
      investigations were normal in the latter two patients (motor, tibial, and median
      somatosensory-evoked potentials in Case 3, and electromyography in both) except
      for the dSEPs. CONCLUSIONS: Objectifying the presence and degree of sensory
      involvement in spinal disorders may be helpful for establishing diagnoses and in
      therapeutic decision-making. Valuable information could be provided by dSEPs in
      selected patients with multiple root or spinal cord involvement.

PMID- 24089997
TI  - Examining the effectiveness of intrathecal baclofen on spasticity in individuals
      with chronic spinal cord injury: a systematic review.
AB  - OBJECTIVE: To review the available evidence on the effectiveness of intrathecal
      baclofen in the treatment of spasticity in individuals with spinal cord injuries
      (SCIs) at least 6 months post-injury or diagnosis. DATA SOURCES: A literature
      search of multiple databases (Pub Med, CINAHL, EMBASE) was conducted to identify
      articles published in the English language. STUDY SELECTION: Studies were
      included for review if: (1) more than 50% of the sample size had suffered a
      traumatic or non-traumatic SCI; (2) there were more than three subjects; (3)
      subjects received continuous intrathecal baclofen via an implantable pump aimed
      at improving spasticity; and (4) all subjects were >=6 months post-SCI, at the
      time of the intervention. DATA EXTRACTION: Data extracted from the studies
      included patient and treatment characteristics, study design, method of
      assessment, and outcomes of the intervention. DATA SYNTHESIS: Methodological
      quality was assessed using the PEDro for randomized-controlled trials (RCTs) and
      the Downs and Black (D&B) tool for non-RCTs. A level of evidence was assigned to
      each intervention using a modified Sackett scale. CONCLUSION: The literature
      search resulted in 677 articles. No RCTs and eight non-RCTs (D&B scores 13-24)
      met criteria for inclusion, providing a pooled sample size of 162 individuals.
      There was substantial level 4 evidence that intrathecal baclofen is effective in
      reducing spasticity. Mean Ashworth scores reduced from 3.1-4.5 at baseline to 1.0
      2.0 (P < 0.005) at follow-up (range 2-41 months). Average dosing increased from
      57-187 ug/day at baseline to 218.7-535.9 ug/day at follow-up. Several
      complications from the use of intrathecal baclofen or pump and catheter
      malfunction were reported.

PMID- 24089998
TI  - Cilostazol-based triple antiplatelet therapy in the era of generic clopidogrel
      and new potent antiplatelet agents.

PMID- 24089996
TI  - The 30-kDa and 38-kDa antigens from Mycobacterium tuberculosis induce partial
      maturation of human dendritic cells shifting CD4(+) T cell responses towards IL-4
      production.
AB  - BACKGROUND: Mycobacterium tuberculosis (Mtb) infections are still a major cause
      of death among all infectious diseases. Although 99% of individuals infected with
      Mtb develop a CD4(+) Th1 and CD8(+) T cell mediated immunity as measured by
      tuberculin skin test, this results only in partial protection and Mtb vaccines
      are not effective. Deviation of immune responses by pathogens towards a Th2
      profile is a common mechanism of immune evasion, typically leading to the
      persistence of the microbes. RESULTS: Here we tested the stimulatory capacity of
      selective Mtb antigens on human monocyte-derived dendritic cell (DC) maturation
      and cytokine production. DC maturation markers CD80, CD86 and CD83 were readily
      upregulated by H37Ra- and H37Rv-associated antigens, the 30-kDa (from Ag85 B
      complex) and 38-KDa Mtb antigens only partially induced these markers. All Mtb
      antigens induced variable levels of IL-6 and low levels of IL-10, there was no
      release of IL-12p70 detectable. Substantial IL-12p40 production was restricted to
      LPS or H37Ra and H37Rv preparations. Although the proliferation levels of primary
      T cell responses were comparable using all the differentially stimulated DC, the
      30-kDa and 38-kDa antigens showed a bias towards IL-4 secretion of polarized
      CD4(+) T cells after secondary stimulation as compared to H37Ra and H37Rv
      preparations. CONCLUSION: Together our data indicate that 30-kDa and 38-kDa Mtb
      antigens induced only partial DC maturation shifting immune responses towards a
      Th2 profile.

PMID- 24089999
TI  - Preference-based Health status in a German outpatient cohort with multiple
      sclerosis.
AB  - BACKGROUND: To prospectively determine health status and health utility and its
      predictors in patients with multiple sclerosis (MS). METHODS: A total of 144 MS
      patients (mean age: 41.0 +/- 11.3 y) with different subtypes (patterns of
      progression) and severities of MS were recruited in an outpatient university
      clinic in Germany. Patients completed a questionnaire at baseline (n = 144), 6
      months (n = 65) and 12 months (n = 55). Health utilities were assessed using the
      EuroQol instrument (EQ-5D, EQ VAS). Health status was assessed by several scales
      (Expanded Disability Severity Scale (EDSS), Modified Fatigue Impact Scale (M
      FIS), Functional Assessment of MS (FAMS), Beck Depression Inventory (BDI-II) and
      Multiple Sclerosis Functional Composite (MSFC)). Additionally, demographic and
      socioeconomic parameters were assessed. Multivariate linear and logistic
      regressions were applied to reveal independent predictors of health status.
      RESULTS: Health status is substantially diminished in MS patients and the EQ VAS
      was considerably lower than that of the general German population. No significant
      change in health-status parameters was observed over a 12-months period.
      Multivariate analyses revealed M-FIS, BDI-II, MSFC, and EDSS to be significant
      predictors of reduced health status. Socioeconomic and socio-demographic
      parameters such as working status, family status, number of household
      inhabitants, age, and gender did not prove significant in multivariate analyses.
      CONCLUSION: MS considerably impairs patients' health status. Guidelines aiming to
      improve self-reported health status should include treatment options for
      depression and fatigue. Physicians should be aware of depression and fatigue as
      co-morbidities. Future studies should consider the minimal clinical difference
      when health status is a primary outcome.

PMID- 24090001
TI  - The complete mitochondrial genome of the Daweizi pig.
AB  - Daweizi pig is one of the famous native breed in China. In this work we reported
      the complete mitochondrial genome sequence of the Daweizi pig in Human Province
      for the first time. The total length of the mitogenome is 16,690 bp, with the
      base composition of 34.68% for A, 25.80% for T, 26.21% for C, 13.31% for G and an
      A + T (60.48%)-rich feature occurs in the Daweizi pig. It is made up of two
      ribosomal RNA genes, 13 protein-coding genes, 22 transfer RNA genes and one non
      coding control region (D-loop region). The arrangement of these genes was the
      same as that found in the Landrace pig. The complete mitochondrial genome
      sequence of the Daweizi pig provides an important data set for further study on
      the germplasm resources.

PMID- 24090000
TI  - A retrospective study of prostate cancer cases mimicking urothelial cell
      carcinoma of the bladder.
AB  - BACKGROUND: Prostate cancer (PCa) originating from the prostate base may intrude
      into the urinary bladder and may be misdiagnosed as bladder cancer. In this
      retrospective study, we reviewed the clinic data on PCa cases which were
      initially misdiagnosed as bladder cancer in order to identify diagnostic methods
      that would allow a better differential diagnosis for PCa. METHODS: Out of a total
      of 455 patients treated for PCa at our hospital between April 2003 and June 2011,
      14 patients (3.1%) had been initially misdiagnosed as urinary bladder urothelial
      cell carcinoma. The clinical data on these 14 cases was retrieved and analyzed.
      RESULTS: Of the 14 patients, 11 patients were eventually diagnosed with PCa after
      MRI examination, and seven out of these had PCa with bladder neck invasion.
      Prostate needle biopsy or transurethral resection of prostate (TURP) revealed
      that all 14 patients had adenocarcinoma of prostate with Gleason scores ranging
      from 7 to 9. Nine patients received TURP for hematuria or lower urinary tract
      blockage. The mean follow-up was 37 months, during which six patients survived.
      CONCLUSIONS: As clinical presentation and in emergency settings, prostate cancer
      originating from the prostate base can be confused with bladder cancer
      originating from the neck or the triangle region of the urinary bladder. Serum
      prostate specific antigen (PSA) levels and digital rectal examination, in
      combination with transrectal ultrasound (TRUS), MRI, and prostate needle biopsy
      are valuable tools for definitive differential diagnosis of the basal prostate
      cancer.

PMID- 24090002
TI  - Complete mitochondrial genome of the Chinese bitterling Rhodeus sinensis
      (Cypriniformes: Cyprinidae).
AB  - The mitochondrial genome of the Chinese bitterling Rhodeus sinesis is a circular
      molecule of 16,677 bp in length, containing 13 protein-coding genes, 22 transfer
      RNA genes, two ribosomal RNA genes and two main non-coding regions (the control
      region and the origin of the light strand replication). The gene composition and
      order of which were similar to most other vertebrates. All protein-coding genes
      are initiated with ATG except for COX 1, which begin with GTG instead. However,
      the termination codons of 13 protein-coding genes are varied with TAA, TA, T or
      TAG. The molecular data we presented here could provide useful information for
      the studies on species identification, evolutionary relationships and population
      genetics of the Acheilognathinae. 

PMID- 24090003
TI  - The complete mitochondrial genome of Pampus punctatissimus (Perciformes:
      Stromateidae).
AB  - The long PCR and primer walking methods are employed for determining the complete
      mitochondrial genome sequence of Pampus punctatissimus. The mitogenome is a
      circular molecule of 16,551 bp in length including the structure of 13 protein
      coding genes, two ribosomal RNA genes, 22 transfer RNA genes and two non-coding
      regions (L-strand replication origin and control region). Within the control
      region, we identify the termination-associated sequence domain (TAS), a central
      conserved domain (CSB-F, CSB-E and CSB-D), and three conserved sequence blocks
      (CSB-1, CSB-2 and CSB-3).

PMID- 24090004
TI  - The complete mitochondrial genome of the Trachinotus ovatus (Teleostei,
      Carangidae).
AB  - We present the complete mitochondrial genome of the Trachinotus ovatus in this
      study. The mitochondrial genome is 16,563 bp long and consists of 13 protein
      coding genes, two rRNA genes, 22 tRNA genes and a control region. The gene order
      and composition of T. ovatus mitochondrial genome was similar to that of most
      other vertebrates. The nucleotide compositions of the light strand are 29.03% of
      A, 28.86% of C, 26.23% of T and 15.88% of G. With the exception of ND6 and eight
      tRNA genes, all other mitochondrial genes are encoded on the heavy strand. Two
      copies of tandem repeat sequence (56 bp) was observed in the 5' end of the
      control region.

PMID- 24090005
TI  - Molecular identification of Pomacea canaliculata and P. insularum from rice paddy
      in different origins in China using mitochondrial adenosine triphosphate subunit
      6 gene.
AB  - To identify Pomacea canaliculata and P. insularum using a molecular approach, the
      partial sequences of mitochondrial (mt) adenosine triphosphate subunit 6 (patp6)
      genes of two apple snails species from eight provinces of China were obtained.
      The intra-specific variations in mt patp6 within P. canaliculata were 0-4.5%, and
      no sequence difference in this region was observed within P. insularum. However,
      high inter-specific variations between P. canaliculata and P. insularum were
      detected, with sequence differences of 8.9-10.1%. Phylogenetic analyses based on
      sequences of mt patp6 revealed that P. canaliculata and P. insularum were grouped
      in different clades, but the genetic trees could not reveal geographically
      genetic relationships of P. canaliculata isolates from different origins. These
      findings will provide basic information for further study of molecular
      epidemiology and control of Pomacea invasion in China as well as in the world. 

PMID- 24090006
TI  - The complete mitochondrial genome of Rhinogobio ventralis (Teleostei, Cyprinidae,
      Gobioninae).
AB  - Rhinogobio ventralis, a small-sized economic fish living in the bottom of the
      fast-flowing water, has a limited geographical distribution in the upper reaches
      of Yangtze River in China. The complete mito-genome of R. ventralis is 16,607 bp
      in length, containing 37 genes of 13 protein-coding genes, 22 tRNA genes, two
      rRNA genes and a control region (D-loop). The gene order and composition of R.
      ventralis is similar to that of most other fishes, and its nucleotide composition
      is 31.10% A, 26.64% T, 26.28% C and 15.98% G, with a slight AT bias of 57.74%. It
      is first report of the complete mitochondrial genome in the bottom dwelling
      Rhinogobio species.

PMID- 24090007
TI  - Mitochondrial genome of the ringstraked guitarfish Rhinobatos hynnicephalus
      (Elasmobranchii: Rajiformes).
AB  - The complete mitochondrial genome of the ringstraked guitarfish Rhinobatos
      hynnicephalus is firstly presented in this study, which is also the first
      representative in the family Rhinobatidae. It is 16,776 bp in length and contains
      37 genes and one control region as the typical gene arrangement and
      transcriptional direction in vertebrates. The overall base composition is 31.7%
      A, 26.8% C, 13.5% G and 28.1% T. The 22 tRNA genes ranged from 67 bp (tRNA-Ser2)
      to 75 bp (tRNA-Leu1). The origin of L-strand replication (OL) sequence was
      identified between tRNA-Asn and tRNA-Cys genes. The termination associated
      sequence (TAS) and the conserved sequence blocks (CSB 1--3) were recognized in
      the control region.

PMID- 24090009
TI  - The economic value of reducing the stigma of HIV/AIDS.

PMID- 24090008
TI  - Biological properties of carotenoids extracted from Halobacterium halobium
      isolated from a Tunisian solar saltern.
AB  - BACKGROUND: Bioactive molecules have received increasing attention due to their
      nutraceutical attributes and anticancer, antioxidant, antiproliferative and
      apoptosis-inducing properties. This study aimed to investigate the biological
      properties of carotenoids extracted from Archaea. METHODS: Halophilic Archaea
      strains were isolated from the brine of a local crystallizer pond (TS7) of a
      solar saltern at Sfax, Tunisia. The most carotenoid-producing strain (M8) was
      investigated on heptoma cell line (HepG2), and its viability was assessed by the
      MTT-test. The cells were incubated with different sub-lethal extract rates, with
      carotenoid concentrations ranging from 0.2 to 1.5 MUM. Antioxidant activity was
      evaluated through exposing the cells to sub-lethal extract concentrations for 24
      hours and then to oxidative stress induced by 60 MUM arachidonic acid and 50 MUM
      H2O2. RESULTS: Compared to non-treated cells, bacterial carotenoid extracts
      inhibited HepG2 cell viability (50%). A time and dose effect was observed, with
      cell viability undergoing a significant (P < 0.05) decrease with extract
      concentration. After exposure to oxidative stress, control cells underwent a
      significant (P < 0.05) decrease in viability as compared to the non-treated
      cells. CONCLUSIONS: The bacterial extracts under investigation were noted to
      exhibit the strongest free radical scavenging activity with high carotenoid
      concentrations. The carotenoid extract also showed significant antiproliferative
      activity against HepG2 human cancer cell lines.

PMID- 24090010
TI  - The physician's breach of the duty to inform the parent of deformities and
      abnormalities in the foetus: "wrongful life" actions, a new frontier of medical
      responsibility.
AB  - A recent decision of the Italian Highest Court for the first time legitimized
      wrongful life suits. The Court stated the following principles: (a) the contract
      between the mother and the doctor has also protective effects in favour of third
      parties (father, siblings and the disabled child) who have the right to be
      compensated; (b) the right to compensation is neither based on the right not to
      be born nor on the right to be born healthy, but rather it is based on the breach
      of duty of care which coincides with the child's disabled status; (c) siblings
      may suffer the reduced availability of their parents; (d) the doctor is held
      responsible for not providing full information to the mother about the foetal
      deformity. The Supreme Court once again emphasized the importance of information
      on the matter of very personal choices, such as termination of pregnancy in case
      of foetal malformations. In the present case, the gynaecologist breached the duty
      to inform, especially after the patient requested diagnostic tests designed to
      highlight any foetal malformations and informed the doctor of the possibility of
      an eventual subsequent termination of pregnancy if foetal malformations were
      found.

PMID- 24090012
TI  - Precut: two (combined techniques) better than one.

PMID- 24090013
TI  - Recurrence of esophageal cancer after R0 surgery. Risk factors and evolution.
AB  - INTRODUCTION: despite advances in surgical and adjuvant therapy, recurrence in
      esophageal cancer submitted to R0 surgery remains high. The aim is to define risk
      factors and recurrence patterns. Additionally, to show the management carried out
      and the outcome of patients showing recurrence. MATERIAL AND METHODS:
      observational and prospective study that included 61 patients. Neoadjuvancy
      therapy was indicated on T3, T4 and N+ tumors and every lymph node dissection was
      performed in two fields. Recurrence is defined at distance, regional or local,
      when, recurrence is detected after six months. According to clinical features and
      the recurrences, a palliative, chemotherapeutic or surgical management was
      indicated. RESULTS: there were 54 men and the mean age was 59.7 years. The most
      frequent stage was the IIA and 17 (27.9%) had positive lymph nodes. Thirty
      (49.2%) had showed recurrence with a median disease-free interval of 10.5 months.
      The pTNM, the absence of response to the neoadjuvancy and the presence of
      compromised lymph nodes were found to be risk factors for recurrence. Only the
      presence of compromised lymph nodes was significant in the multivariate analysis.
      After diagnosis of the recurrence, median survival was 7 months and 6 subjects
      survived beyond 1 year. CONCLUSIONS: we confirmed the high incidence of
      recurrence in esophageal cancer, where the presence of compromised lymph nodes is
      probably the main risk factor. After the diagnosis of a relapse the prognosis
      would be bad, however there would be a small subsidiary group for treatment where
      outcomes would be better.

PMID- 24090011
TI  - Capecitabine and bevacizumab for non-resectable metastatic colorectal cancer
      patients: final results from phase II AIO KRK 0105 trial.
AB  - BACKGROUND: Current guidelines recommend treatment with capecitabine and
      bevacizumab for patients (pts) with non-resectable metastatic colorectal cancer
      (mCRC), although clinical data in this particular patient group are lacking.
      METHODS: Previously untreated patients with non-resectable mCRC were to receive
      capecitabine (1,250 mg/sqm bid d1-14 oral) and bevacizumab (7.5 mg/kg i.v.) every
      3 weeks. Progression-free survival (PFS) was the primary endpoint. Secondary
      endpoints include overall survival (OS), objective response rate (ORR) and
      toxicity. RESULTS: 82 pts were included: 40 female, median age 70 (range 50-86).
      ECOG PS 0/1/2 was 38/52/10%, respectively. Synchronous metastases were present in
      58 pts. 16 pts had primary tumor in situ. Median treatment duration was 4.1
      months (6 cycles). Toxicity was generally mild. ORR was 38%, with 5 complete and
      23 partial responses. Median PFS was 7.0 months [95% CI (5.0-9.1)] and OS 17.9
      months [95% CI (14.6-21.6)]. Second- and third-line systemic therapy was given to
      57% and 33% of pts, respectively. CONCLUSIONS: Besides the favourable
      tolerability, PFS and OS were shorter than reported by other trials. Careful
      patient selection for upfront capecitabine and bevacizumab is essential.

PMID- 24090014
TI  - Endoscopic and histological pitfalls in the diagnosis of celiac disease: A
      multicentre study assessing the current practice.
AB  - BACKGROUND AND AIMS: the diagnosis of celiac disease requires small bowel
      biopsies to identify the characteristic mucosal changes. The current biopsy
      practice among endoscopists for celiac disease is in most part unknown. The aim
      of this study was to compare the different diagnostic policies in various centers
      in their current practice. METHOD: information from a total of 931 confirmed
      celiac disease patients was retrospectively obtained retrospectively from nine
      centers in European and Middle Eastern countries. The number of small-bowel
      biopsies obtained from the duodenal bulb and the second part of the duodenum was
      compared among different centers. RESULTS: the most frequent stage of mucosal
      changes amongst Iranian subjects was Marsh IIIa whereas in the rest of the study
      population was Marsh IIIc. Marsh I and Marsh II were more prevalent in adults (P
      < 0.05) and Marsh IIIc was significantly higher in pediatric ages between 1 and
      15 (P < 0.05). The most common number of biopsy specimens obtained from Romanian
      subjects was 1 (52% of cases), followed by 2 for Iranian (56%), 3 for Lithuanian
      (66.7%) and British patients (65%) and 4 for Italian patients (48.3%). For
      majority of cases, anemia was the most prevalent symptom (18.7%) followed by
      malabsorption (10.5%), diarrhea (9.3%) and dyspepsia (8.2%), respectively.
      CONCLUSIONS: despite the evidence-based recommendations, this study revealed a
      poor compliance with major guidelines on diagnosis of celiac disease. We
      emphasize that taking adequate number of duodenal biopsies should be implemented
      for an accurate diagnosis and also for the exclusion of celiac disease.

PMID- 24090015
TI  - Combined precut in difficult biliary cannulation.
AB  - AIM: precut sphincterotomy refers to a variety of endoscopic techniques that are
      used in order to access the bile duct when conventional methods of cannulation
      have failed. There are not significant data (such as efficacy, safety) about the
      use of different techniques of precutting at the same session. We have described
      our experience with combined precut sphincterotomy (CPS) and we have compared our
      results to the use of an isolated precut. PATIENTS AND METHODS: we have performed
      247 precuts of a total of 2.390 ERCPs. Patients were distributed according to the
      type of precut practiced: Needle-knife, transpancreatic and combined precut
      sphincterotomies. "Combined precut" consisted in performing first a
      transpancreatic sphincterotomy and, if the access was not achieved, then
      performing a needle-knife sphincterotomy in the same session. The data about
      safety and efficacy were prospectively collected. The complications were defined
      according to the consensus criteria. RESULTS: we performed precutting techniques
      in 247 patients. Needle-knife, transpancreatic, and combined precuts were
      performed in 125 (6.9%), 74 (4.1%) and 48 (2.6%) patients, respectively. Bile
      duct cannulation was successful in 48 patients (100%) in the group of combined
      precut, 121 patients (96.8%) in the transpancreatic group, and 67 patients
      (90.5%) in the needleknife group (p = 0.03). There were not differences in
      complications rates between the three groups. There was no pancreatitis in the
      combined precut group. The complications were successfully managed with
      conservative treatment. CONCLUSIONS: combined precut sphincterotomy seems to be a
      safe and successful technique in those cases of difficult bile duct cannulation.

PMID- 24090016
TI  - Impact of combined precut techniques on selective biliary cannulation.
AB  - INTRODUCTION: simple biliary cannulation techniques obtain a success rate of 80
      95%. Advanced precut techniques are not immediately successful in 10-40% of
      cases. Between extreme options such as a second attempt a few days later or an
      immediate attempt by the transparietal route, an alternative precut technique may
      be used as a rescue strategy for the initially failed procedure. The purpose of
      this study was to assess the efficacy and safety of the combined use of two
      precut techniques when immediate biliary access is not granted by an initial
      procedure. PATIENTS AND METHOD: a retrospective analysis of a personal series of
      precut (needle-knife and transpancreatic) sphincterotomies, both alone and in
      combination. RESULTS: five hundred sixty nine ERCPs (endoscopic retrograde
      cholangio-pancreatography) met the inclusion criteria for the analysis. Simple
      cannulation was obtained in 444 (78%) of them. In all, 119 (21%) precuts were
      attempted and 110 (92.4%) were successful, which raised the overall cannulation
      rate to 97.4%. Ninety-five (80%) precuts were successful with the initial
      technique. Rescue with the alternative technique was attempted for 20 failures
      with a successful outcome in 15, which raised the overall success rate to 92%.
      The combination of needle-knife precut plus transpancreatic precut raised the
      success rate from 87% to 94%. The combination of transpancreatic precut plus
      needle-knife precut raised the success rate from 70% to 90%. Among all 96
      patients with available follow-up data, 17 (18%) complications were recorded: 9
      bleeding episodes, 4 pancreatitis cases, and 4 retroperitoneal perforations. No
      mortality was recorded. CONCLUSIONS: a combination of precut techniques is
      effective for biliary cannulation when simple cannulation and initial precut
      approaches fail. The safety profile differs from that in the delayed strategy,
      hence both should be considered alternatives, their use depending on the
      technical and clinical conditions prevailing for each patient, as well as
      endoscopist experience.

PMID- 24090017
TI  - Linaclotide in the treatment of patients with irritable bowel syndrome and
      constipation - analysis of an opportunity.
AB  - Linaclotide is a secretagogue that provides a combined effect on visceral pain.
      The European Medicines Agency has authorized its indication for the symptomatic
      treatment of moderate to severe irritable bowel syndrome with constipation in
      adults. The purpose of this review is to discuss the clinical framework for
      linaclotide use in our setting, the drug's characteristics and pre-clinical
      development, and the clinical studies supporting its use in order to establish
      relevant views regarding its validity and clinical applicability. The results
      suggest that the only -non-severe- adverse effect associated with this drug is
      diarrhea. As regards effectiveness, linaclotide consistently shows favorable,
      significant differences in absolute risk versus placebo for all objective outcome
      variables described by regulatory agencies, with a combined pain and constipation
      response between 12.6% and 22.8% according to the variable and trial under
      consideration. This response is sustained and drug-related, as it goes away upon
      discontinuation. To conclude, linaclotide has a safety and efficacy profile that,
      from a clinical perspective, warrants its use for patients meeting irritable
      bowel syndrome and constipation criteria, with significant symptoms that cannot
      be relieved with other less specific measures. In the absence of predictive rules
      for response, it is recommended that, should the patient fail to respond, he or
      she should be considered not eligible for linaclotide therapy, and both
      indication and treatment continuity should be reserved for objective responders
      alone.

PMID- 24090018
TI  - Non granular laterally spreading tumor resected by endoscopic submucosal
      dissection: An unusual treatment for an atypical lesion.

PMID- 24090019
TI  - Biliary peritonitis secondary to spontaneous rupture of hepatic mesenchymal
      hamartoma.

PMID- 24090020
TI  - Budd-Chiari syndrome secondary to inflammatory pseudotumor of the liver: Report
      of a case with a 10-year follow-up.
AB  - Inflammatory pseudotumor (IPT) of the liver is a rare benign tumor of unknown
      origin, it has the appearance of a malignant tumor but has a benign histology and
      clinical course. We report a case of a 63-year-old man diagnosed of IPT of the
      liver and followed for 10 years. During the clinical course, he developed a
      secondary Budd-Chiari syndrome, with a successful response to a transjugular
      intrahepatic portosystemic shunt over a 5-year follow-up period. 

PMID- 24090021
TI  - Transhepatic anterograde biliary drainage using a self-expandable metallic stent:
      A therapeutic alternative after hepaticojejunostomy with Roux-en-Y
      reconstruction.
AB  - Endoscopic drainage is the procedure of choice in cases of obstructive jaundice.
      However, in patients with a surgical biliary reconstruction, this technique
      cannot be often satisfactorily used. In these cases, the best alternative has
      usually been the percutaneous biliary drainage. Since the introduction of
      endoscopic ultrasoundguided therapy, some new techniques have been proposed to
      solve these technical problems related to postsurgical disturbed anatomy. In this
      case report, we describe our successful experience in the performance of a
      transhepatic anterograde biliary drainage using a self-expandable metallic stent
      in the context of a patient who previously had undergone a hepaticojejunostomy
      with Roux-en-Y reconstruction because of a resected hilar cholangiocarcinoma. 

PMID- 24090022
TI  - [Hepatopulmonar syndrome].

PMID- 24090023
TI  - Giant hepatic hydatid cyst with mediastinal extension.

PMID- 24090024
TI  - Duodenal diverticulum perforated by foreign body.

PMID- 24090025
TI  - Rectal perforation associated with sunitinib therapy.

PMID- 24090026
TI  - Menetrier's disease and Kaposi's sarcoma in a HIV-positive patient.

PMID- 24090027
TI  - Inappropriate use of proton pump inhibitors, guidelines and clinical research.

PMID- 24090029
TI  - Evaluation of the causal framework used for setting national ambient air quality
      standards.
AB  - Abstract A scientifically sound assessment of the potential hazards associated
      with a substance requires a systematic, objective and transparent evaluation of
      the weight of evidence (WoE) for causality of health effects. We critically
      evaluated the current WoE framework for causal determination used in the United
      States Environmental Protection Agency's (EPA's) assessments of the scientific
      data on air pollutants for the National Ambient Air Quality Standards (NAAQS)
      review process, including its methods for literature searches; study selection,
      evaluation and integration; and causal judgments. The causal framework used in
      recent NAAQS evaluations has many valuable features, but it could be more
      explicit in some cases, and some features are missing that should be included in
      every WoE evaluation. Because of this, it has not always been applied
      consistently in evaluations of causality, leading to conclusions that are not
      always supported by the overall WoE, as we demonstrate using EPA's ozone
      Integrated Science Assessment as a case study. We propose additions to the NAAQS
      causal framework based on best practices gleaned from a previously conducted
      survey of available WoE frameworks. A revision of the NAAQS causal framework so
      that it more closely aligns with these best practices and the full and consistent
      application of the framework will improve future assessments of the potential
      health effects of criteria air pollutants by making the assessments more
      thorough, transparent, and scientifically sound. 

PMID- 24090030
TI  - Simultaneous screening analysis of 3-methyl-quinoxaline-2-carboxylic acid and
      quinoxaline-2-carboxylic acid residues in edible animal tissues by a competitive
      indirect immunoassay.
AB  - Immunoassays contribute greatly to food safety. Yet there are no reported
      immunoassays that simultaneously detect MQCA and QCA, the marker residues for
      olaquindox and carbadox, respectively. Here, a broad-specificity mAb was
      successfully produced, and the mAb showed good cross-reactivity with both MQCA
      and QCA, having IC50 values in buffer of 4.8 and 9.6 ng/mL, respectively. The
      calibration curves ranged from 0.3 to 81 MUg/kg. The average recoveries ranged
      from 76% to 108% at different spiked levels (2, 4, and 8 MUg/kg for MQCA; and 4,
      10, and 20 MUg/kg for QCA), and the intra-/interday coefficients of variation
      were 4.2-13.3%. The limits of detection of MQCA and QCA in chicken, fish, pork,
      and shrimp were 1.76, 1.32, 1.90, and 1.18 MUg/kg, respectively. This method was
      verified by LC-MS/MS, with a correlation coefficient above 0.98. The immunoassay
      was rapid and reliable for simultaneous screening analysis of MQCA and QCA
      residues. 

PMID- 24090032
TI  - Mspire-Simulator: LC-MS shotgun proteomic simulator for creating realistic gold
      standard data.
AB  - The most important step in any quantitative proteomic pipeline is feature
      detection (aka peak picking). However, generating quality hand-annotated data
      sets to validate the algorithms, especially for lower abundance peaks, is nearly
      impossible. An alternative for creating gold standard data is to simulate it with
      features closely mimicking real data. We present Mspire-Simulator, a free, open
      source shotgun proteomic simulator that goes beyond previous simulation attempts
      by generating LC-MS features with realistic m/z and intensity variance along with
      other noise components. It also includes machine-learned models for retention
      time and peak intensity prediction and a genetic algorithm to custom fit model
      parameters for experimental data sets. We show that these methods are applicable
      to data from three different mass spectrometers, including two fundamentally
      different types, and show visually and analytically that simulated peaks are
      nearly indistinguishable from actual data. Researchers can use simulated data to
      rigorously test quantitation software, and proteomic researchers may benefit from
      overlaying simulated data on actual data sets. 

PMID- 24090031
TI  - Poly(ethylene glycol)- and carboxylate-functionalized gold nanoparticles using
      polymer linkages: single-step synthesis, high stability, and plasmonic detection
      of proteins.
AB  - Gold nanoparticles with suitable surface functionalities have been widely used as
      a versatile nanobioplatform. However, functionalized gold nanoparticles using
      thiol-terminated ligands have a tendency to aggregate, particularly in many
      enzymatic reaction buffers containing biological thiols, because of ligand
      exchange reactions. In the present study, we developed a one-step synthesis of
      poly(ethylene glycol) (PEG)ylated gold nanoparticles using
      poly(dimethylaminoethyl methacrylate) (PDMAEMA) in PEG as a polyol solvent.
      Because of the chelate effect of polymeric functionalities on the gold surface,
      the resulting PEGylated gold nanoparticles (Au@P-PEG) are very stable under the
      extreme conditions at which the thiol-monolayer-protected gold nanoparticles are
      easily coagulated. Using the solvent mixture of PEG and ethylene glycol (EG) and
      subsequent hydrolysis, gold nanoparticles bearing mixed functionalities of PEG
      and carboxylate are generated. The resulting particles exhibit selective
      adsorption of positively charged chymotrypsin (ChT) without nonselective
      adsorption of bovine serum albumin (BSA). The present nanoparticle system has
      many advantages, including high stability, simple one-step synthesis,
      biocompatibility, and excellent binding specificity; thus, this system can be
      used as a versatile platform for potential bio-related applications, such as
      separation, sensing, imaging, and assays. 

PMID- 24090033
TI  - Home administration of maintenance pemetrexed for patients with advanced non
      squamous non-small cell lung cancer: rationale, practicalities and phase II
      feasibility study design.
AB  - BACKGROUND: Home-based care in oncology is mainly reserved for patients at the
      end of life. Regulations regarding home delivery of cytotoxics differ across
      Europe, with a notable lack of practice guidelines in most countries. This has
      led to a lack of data addressing the feasibility of home-based administration of
      cytotoxic chemotherapy. In advanced non-squamous non-small cell lung cancer,
      pemetrexed is approved as maintenance therapy after first-line chemotherapy. In
      this setting, patients have the potential to be treated long-term with
      maintenance therapy, which, in the absence of unacceptable toxicity, is continued
      until disease progression. The favourable safety profile of pemetrexed and the
      ease of its administration by 10-minute intravenous infusion every 3 weeks make
      this drug a suitable candidate for administration in a home setting. METHODS:
      Literature and regulations relevant to the home-based delivery of cytotoxic
      therapy were reviewed, and a phase II feasibility study of home administration of
      pemetrexed maintenance therapy was designed. At least 50 patients with advanced
      non-squamous non-small cell lung cancer, Eastern Cooperative Oncology Group
      performance status 0-1 and no progressive disease after four cycles of platinum
      based first-line therapy are required to allow investigation of the feasibility
      of home-based administration of pemetrexed maintenance therapy (500 mg/m(2) every
      3 weeks until progressive disease or unacceptable toxicity). Feasibility is being
      assessed as adherence to the home-based administration process (primary
      endpoint), patient safety, impact on patients' quality of life, patient and
      physician satisfaction with home care, and healthcare resource use and costs.
      Enrolment of patients from the UK and Sweden, where home-based care is relatively
      well developed, commenced in December 2011. DISCUSSION: This feasibility study
      addresses an important aspect of maintenance therapy, that is, patient comfort
      during protracted home-based chemotherapy. The study design requires unusual
      methodology and specific logistics to address outcomes relevant to the home
      delivery approach. This article presents a study design that offers a novel and
      reproducible model for home-based chemotherapy, and provides an up-to-date
      overview of the literature regarding this type of treatment. TRIAL REGISTRATION:
      ClinicalTrials.gov: NCT01473563.

PMID- 24090034
TI  - Conjugates of amino acids and peptides with 5-o-mycaminosyltylonolide and their
      interaction with the ribosomal exit tunnel.
AB  - During protein synthesis the nascent polypeptide chain (NC) extends through the
      ribosomal exit tunnel (NPET). Also, the large group of macrolide antibiotics
      binds in the nascent peptide exit tunnel. In some cases interaction of NC with
      NPET leads to the ribosome stalling, a significant event in regulation of
      translation. In other cases NC-ribosome interactions lead to pauses in
      translation that play an important role in cotranslational folding of
      polypeptides emerging from the ribosome. The precise mechanism of NC recognition
      in NPET as well as factors that determine NC conformation in the ribosomal tunnel
      are unknown. A number of derivatives of the macrolide antibiotic 5-O
      mycaminosyltylonolide (OMT) containing N-acylated amino acid or peptide residues
      were synthesized in order to study potential sites of NC-NPET interactions. The
      target compounds were prepared by conjugation of protected amino acids and
      peptides with the C23 hydroxyl group of the macrolide. These OMT derivatives
      showed high although varying abilities to inhibit the firefly luciferase
      synthesis in vitro. Three glycil-containing derivatives appeared to be strong
      inhibitors of translation, more potent than parental OMT. Molecular dynamics (MD)
      simulation of complexes of tylosin, OMT, and some of OMT derivatives with the
      large ribosomal subunit of E. coli illuminated a plausible reason for the high
      inhibitory activity of Boc-Gly-OMT. In addition, the MD study detected a new
      putative site of interaction of the nascent polypeptide chain with the NPET
      walls. 

PMID- 24090035
TI  - Quenching the chemiluminescence of acridinium ester by graphene oxide for label
      free and homogeneous DNA detection.
AB  - It was found that graphene oxide (GO) could effectively quench the
      chemiluminescence (CL) emission from a acridinium ester (AE)-hydrogen peroxide
      system. By taking advantage of this quenching effect, as a proof of concept, a
      label-free and homogeneous DNA assay was developed for the detection of
      Mycobacterium tuberculosis DNA. In the absence of target DNA, both probe DNA and
      AE were absorbed on the surface of GO, producing a weak CL emission owing to the
      CL quenching effect of GO. However, in the presence of target DNA, a double
      stranded structure of DNA was generated, leading to the release of the
      oligonucleotide from the GO surface. AE favors binding with double-stranded DNA,
      which will be released from the GO surface; thus, the quenching effect of GO will
      be no longer effective and a strong CL signal can be observed. This assay can
      detect M. tuberculosis DNA with a detection limit of 0.65 nM. This sensitivity is
      lower than that of previously reported electrochemical detection. 

PMID- 24090036
TI  - Use patterns of long-acting bronchodilators in routine COPD care: the OUTPUL
      study.
AB  - BACKGROUND: COPD is the fourth leading cause of death in the world. In the case
      of exacerbations or persistent symptoms, regular treatment with long-acting
      bronchodilators is recommended to control the symptoms, reduce exacerbations and
      improve health status. Objectives. To describe patterns of drug utilization among
      patients diagnosed with COPD, to measure continuity with long-acting
      bronchodilators, to identify determinants of not receiving long-acting therapy
      continuously. METHODS: We identified a cohort of patients discharged from
      hospital with diagnosis of COPD between 2006 and 2008. Patients were observed for
      a two-year follow-up period, starting from the day of discharge. Follow-up was
      segmented in six-month periods, in order to dynamically evaluate prescription
      patterns of Long-Acting Beta-Agonists (LABA), tiotropium, and inhaled
      corticosteroids. Patients with prescriptions for LABA and/or tiotropium in each
      of the six-month periods were defined as "continuously treated with long-acting
      bronchodilators." The degree of drug treatment coverage was measured through the
      Medication Possession Ratio (MPR). Logistic regression was performed to identify
      determinants of not receiving long-acting bronchodilators continuously. RESULTS:
      A total of 11,452 patients diagnosed with COPD were enrolled. Only 34.8% received
      long-acting bronchodilators continuously. The MPR was greater than 75% in 19.6%
      of cases. Among the determinants of not receiving long-acting bronchodilators
      continuously, older age and co-morbidities played an important role. CONCLUSIONS:
      In clinical practice, the COPD pharmacotherapy is not consistent with clinical
      guidelines. Medical education is needed to disseminate evidence-based prescribing
      patterns for COPD, and to raise awareness among physicians and patients on the
      health benefits of an appropriate pharmacological treatment.

PMID- 24090037
TI  - Analysis of middle cerebral artery peak systolic velocity in monochorionic twin
      pregnancies as a method for identifying spontaneous twin anaemia-polycythaemia
      sequence.
AB  - A regular Doppler control evaluation of middle cerebral artery peak systolic
      velocity is needed in order to identify twin anaemia polycythaemia sequence in
      monochorionic twin pregnancies. Here, we present a clinical case of spontaneous
      TAPS, and we review the diagnostic criteria and management strategies for this
      syndrome.

PMID- 24090038
TI  - Apathy correlates with cognitive performance, functional disability, and HIV RNA
      plasma levels in HIV-positive individuals.
AB  - We examined the relationship of apathy with neurocognitive performance, age,
      disease markers, and functional disability in 116 HIV-infected individuals.
      Apathy was assessed with the Apathy Evaluation Scale and was significantly
      associated with highest HIV plasma level, functional disability, and
      neurocognitive performance. Individuals with higher apathy levels demonstrated a
      stronger association between age and processing speed performance. Our findings
      suggest that apathy is related to poor neuropsychological functioning, HIV plasma
      levels, and increased functional disability in individuals with HIV.
      Additionally, to our knowledge, this is the first study to demonstrate an
      interactive effect of age and apathy on neuropsychological performance in HIV. 

PMID- 24090039
TI  - A randomized controlled pilot trial comparing the impact of access to clinical
      endocrinology video demonstrations with access to usual revision resources on
      medical student performance of clinical endocrinology skills.
AB  - BACKGROUND: Demonstrating competence in clinical skills is key to course
      completion for medical students. Methods of providing clinical instruction that
      foster immediate learning and potentially serve as longer-term repositories for
      on-demand revision, such as online videos demonstrating competent performance of
      clinical skills, are increasingly being used. However, their impact on learning
      has been little studied. The aim of this study was to determine the value of
      adjunctive on-demand video-based training for clinical skills acquisition by
      medical students in endocrinology. METHODS: Following an endocrinology clinical
      tutorial program, 2nd year medical students in the pre-assessment revision period
      were recruited and randomized to either a set of bespoke on-line clinical skills
      training videos (TV), or to revision as usual (RAU). The skills demonstrated on
      video were history taking in diabetes mellitus (DMH), examination for diabetes
      lower limb complications (LLE), and examination for signs of thyroid disease
      (TE). Students were assessed on these clinical skills in an observed structured
      clinical examination two weeks after randomization. Assessors were blinded to
      student randomization status. RESULTS: For both diabetes related clinical skills
      assessment tasks, students in the TV group performed significantly better than
      those in the RAU group. There were no between group differences in thyroid
      examination performance. For the LLE, 91.7% (n = 11/12) of students randomized to
      the video were rated globally as competent at the skill compared with 40% (n =
      4/10) of students not randomized to the video (p = 0.024). For the DMH, 83.3% (n
      = 10/12) of students randomized to the video were rated globally as competent at
      the skill compared with 20% (n = 2/10) of students not randomized to the video (p
      = 0.007). CONCLUSION: Exposure to high quality videos demonstrating clinical
      skills can significantly improve medical student skill performance in an observed
      structured clinical examination of these skills, when used as an adjunct to
      clinical skills face-to-face tutorials and deliberate practice of skills in a
      blended learning format. Video demonstrations can provide an enduring, on-demand,
      portable resource for revision, which can even be used at the bedside by
      learners. Such resources are cost-effectively scalable for large numbers of
      learners.

PMID- 24090040
TI  - Rat pulmonary responses to inhaled nano-TiO2: effect of primary particle size and
      agglomeration state.
AB  - BACKGROUND: The exact role of primary nanoparticle (NP) size and their degree of
      agglomeration in aerosols on the determination of pulmonary effects is still
      poorly understood. Smaller NP are thought to have greater biological reactivity,
      but their level of agglomeration in an aerosol may also have an impact on
      pulmonary response. The aim of this study was to investigate the role of primary
      NP size and the agglomeration state in aerosols, using well-characterized TiO2
      NP, on their relative pulmonary toxicity, through inflammatory, cytotoxic and
      oxidative stress effects in Fisher 344 male rats. METHODS: Three different sizes
      of TiO2 NP, i.e., 5, 10-30 or 50 nm, were inhaled as small (SA) (< 100 nm) or
      large agglomerates (LA) (> 100 nm) at 20 mg/m3 for 6 hours. RESULTS: Compared to
      the controls, bronchoalveolar lavage fluids (BALF) showed that LA aerosols
      induced an acute inflammatory response, characterized by a significant increase
      in the number of neutrophils, while SA aerosols produced significant oxidative
      stress damages and cytotoxicity. Data also demonstrate that for an agglomeration
      state smaller than 100 nm, the 5 nm particles caused a significant increase in
      cytotoxic effects compared to controls (assessed by an increase in LDH activity),
      while oxidative damage measured by 8-isoprostane concentration was less when
      compared to 10-30 and 50 nm particles. In both SA and LA aerosols, the 10-30 nm
      TiO2 NP size induced the most pronounced pro-inflammatory effects compared to
      controls. CONCLUSIONS: Overall, this study showed that initial NP size and
      agglomeration state are key determinants of nano-TiO2 lung inflammatory reaction,
      cytotoxic and oxidative stress induced effects.

PMID- 24090042
TI  - Performance of five molecular methods for monitoring Arcobacter spp.
AB  - BACKGROUND: Bacteria belonging to the Arcobacter genus are emerging
      enteropathogens and potential zoonotic agents. Their taxonomy has evolved very
      rapidly, and there are presently 18 recorded species. The prevalence of species
      belonging to Arcobacter is underestimated because of the limitations of currently
      available methods for species identification.The aim of this study was to compare
      the performance of five PCR based methods that target regions of 16S rRNA, 23S
      rRNA or gyrA genes to identify Arcobacter species, and to review previous results
      reported in the literature using these methods. RESULTS: The five tested methods
      were found not to be reliable. They misidentified between 16.8% and 67.4% of the
      studied strains; this was dependent upon the target regions of the tested genes.
      The worst results obtained were for the identification of Arcobacter
      cryaerophilus and Arcobacter butzleri when the 23S rRNA gene was used as the
      target. These species were confused with many non-targeted species. CONCLUSION:
      Our results suggest that the known diversity of Arcobacter spp. in different
      environments could be expanded if reliable identification methods are applied in
      future studies.

PMID- 24090043
TI  - Co-infections with Babesia microti and Plasmodium parasites along the China
      Myanmar border.
AB  - BACKGROUND: Babesiosis is an emerging health risk in several parts of the world.
      However, little is known about the prevalence of Babesia in malaria-endemic
      countries. The area along the China-Myanmar border in Yunnan is a main endemic
      area of malaria in P.R. China, however, human infection with Babesia microti (B.
      microti) is not recognized in this region, and its profile of co-infection is not
      yet clear. METHODS: To understand its profile of co-infections with B. microti,
      our investigation was undertaken in the malaria-endemic area along the China
      Myanmar border in Yunnan between April 2012 and June 2013. Four parasite species,
      including B. microti, Plasmodium falciparum (P. falciparum), P. vivax, and P.
      malariae, were identified among 449 suspected febrile persons detected by nested
      polymerase chain reaction (PCR) assay based on small subunit ribosomal
      ribonucleic acid (RNA) genes of B. microti and Plasmodium spp. RESULTS: Of all
      the collected samples from febrile patients, mono-infection with B. microti, P.
      vivax, P. falciparum, and P. malariae accounted for 1.8% (8/449), 9.8% (44/449),
      2.9% (13/449), and 0.2% (1/449), respectively. The rate of mixed infections of B.
      microti with P. falciparum or P. vivax are both 0.2% (1/449), and mixed
      infections of P. falciparum and P. vivax accounted for 1.1% (5/449). CONCLUSIONS:
      This report supports the hypothesis that babesiosis caused by B. microti is
      emerging along the China-Myanmar border in the Yunnan province, P.R. China, but
      it was ignored because of low parasitemia or mixed infection with Plasmodium spp.
      More sensitive and specific diagnosis methods are needed to find the rapid
      response mechanism of emergency for babesiosis and malaria co-prevalence areas.

PMID- 24090044
TI  - New cationic and neutral Ru(II)- and Os(II)-dmso carbonyl compounds.
AB  - The preparation and structural characterization of three cationic Ru(II)-dmso
      carbonyls and of four neutral mono- and dicarbonyl Os(II)-dmso derivatives is
      reported. The two monocarbonyl species fac-[Ru(CO)(dmso-O)3(dmso-S)2][PF6]2 (11)
      and cis,cis,cis-[RuCl(CO)(dmso-O)2(dmso-S)2][PF6] (12) were obtained from the
      neutral monocarbonyl precursor cis,trans,cis-[RuCl2(CO)(dmso-O)(dmso-S)2] (3)
      upon stepwise replacement of the chlorides with dmso, that binds in each case
      through the oxygen atom. The dicarbonyl cationic complex cis,cis,trans
      [Ru(CO)2(dmso-O)2(dmso-S)Cl][PF6] (13) was instead obtained upon treatment of the
      neutral tricarbonyl precursor fac-[RuCl2(CO)3(dmso-O)] (8) with AgPF6 in the
      presence of DMSO: replacement of a Cl(-) with a dmso-O implied also the
      substitution of one CO ligand by another dmso (that binds through S trans to Cl).
      The Os(II) carbonyls trans,trans,trans-[OsCl2(CO)(dmso-O)(dmso-S)2] (17),
      trans,cis,cis-[OsCl2(CO)2(dmso-O)2] (18), cis,mer-[OsCl2(CO)(dmso-S)3] (19), and
      cis,trans,cis-[OsCl2(CO)(dmso-O)(dmso-S)2] (20) were obtained by treatment of the
      Os(II)-dmso precursors trans-[OsCl2(dmso-S)4] (14) and cis,fac-[OsCl2(dmso
      O)(dmso-S)3] (15) with CO. Each one of them is structurally similar to an already
      known Ru(II) analog, even though--in agreement with the expected greater
      inertness of Os(II)--more forcing reaction conditions were required for their
      preparation. Interestingly, compound 20 could not be isolated in pure form, but
      only as a 1:1 cocrystallized mixture with its precursor 15. The dmso ligand is
      always bound through the oxygen atom when trans to CO. We are confident that the
      new Ru(II)- and Os(II)-dmso carbonyl species described here represent a
      contribution to expand the pool of complexes bearing some easily replaceable dmso
      ligands to be used as well-behaved precursors in inorganic synthesis.

PMID- 24090045
TI  - Can the pharmaceutical industry embrace comparative effectiveness research? A
      view from inside.

PMID- 24090046
TI  - Salmonella prostatitis in a man with spinal cord injury.
AB  - CONTEXT: Prostatitis is a very unusual manifestation of Salmonella urinary tract
      infection and has not been reported in men with spinal cord injury (SCI).
      FINDINGS: A 57-year-old man with paraplegia and a history of recurrent
      symptomatic urinary tract infections presented with Salmonella typhimurium
      prostatitis. Clinical and sonographic examination of the urinary tract, as well
      as urinalysis including microbiologic examination, revealed no relevant
      abnormalities. The microbiologic analysis of the ejaculate revealed growth of
      monophasic Salmonella enterica ssp. enterica serotype 4,12:i:-. A 6-week course
      of antibiotic treatment was initiated. There were no recurrent symptomatic
      urinary tract infections during follow-up. CONCLUSION: Salmonellosis is a
      reportable disease and carriers have to refrain from activities in the food
      sector. Therefore, Salmonella prostatitis should be considered and excluded in
      men with SCI and a history of recurrent urinary tract infection who use
      intermittent catheterization for bladder management.

PMID- 24090047
TI  - Japan useful medication program for schizophrenia (JUMPs)-long-term study on
      discontinuation rate, resolution and remission, and improvement in social
      functioning rate associated with atypical antipsychotic medications in patients
      with schizophrenia.
AB  - BACKGROUND: It is desirable to establish evidence for the selection of
      antipsychotics from the viewpoint of recovery of social activity in individual
      patient with schizophrenia receiving medication. From this perspective, awareness
      of the importance of studies about drug effectiveness on treatment
      discontinuation rate, remission rate, and improvement in QOL has grown recently.
      In Western countries, numerous reports are available in effectiveness studies,
      which are related to olanzapine and risperidone primarily, whereas evidence for
      other second-generation antipsychotics (SGAs) is poor. In Japan, no effectiveness
      study has been reported: thus, it is desirable to collect data that will serve as
      evidence for selection of the 3 SGAs approved after olanzapine. METHODS: The
      present study was a long-term effectiveness study under healthcare setting in
      Japan. It was designed as an open-label, multicenter, randomized, comparative
      study involving 104-week oral treatment with 1 of the 3 drugs (aripiprazole,
      blonanserin, and paliperidone) in patients with schizophrenia aged 20 years or
      over who required antipsychotic medication or switching of the current medication
      to others for reasons such as lack of efficacy and intolerability. The primary
      endpoint is treatment discontinuation rate for any causes. The secondary
      endpoints include remission rate, improvement of social activity, alleviation,
      aggravation or recurrence of psychiatric symptoms, and safety. The target number
      of subjects was set at 300. DISCUSSION: Because this study is expected to yield
      evidence regarding the selection of antipsychotics for facilitating the recovery
      of social activity in patients with schizophrenia, it is considered highly
      valuable to perform this effectiveness study under ordinary healthcare setting in
      Japan. TRIAL REGISTRATION: UMIN Clinical Trials Registry 000007942.

PMID- 24090048
TI  - Exposure of fatty acids after a single oral administration of sacha inchi
      (Plukenetia volubilis L.) and sunflower oil in human adult subjects.
AB  - CONTEXT: Sacha inchi (Plukenetia volubilis L.) is a potential oilseed crop
      because it is rich in alpha-linolenic acid (ALA) (omega-3 fatty acid). OBJECTIVE:
      To evaluate the exposure of fatty acids after a single oral administration of
      sacha inchi or sunflower oil in healthy volunteers. MATERIAL AND METHODS: Plasma
      fatty acids concentrations were assayed by Gas Chromatography with Flame
      Ionization Detector in 18 adult subjects. After fasting, blood samples were
      obtained at 0, 0.5, 1, 2, 4, 8 and 24 h after ingestion of 10 or 15 ml of sacha
      inchi oil or sunflower oil. RESULTS: The proportion ALA/linoleic acid was 1.37 in
      sacha inchi oil and 0.01 in sunflower oil. ALA, lauric acid, palmitic acid,
      linolelaidic acid, cis-8,11,14-eicosatrienoic acid, cis-13,16-docosadienoic acid
      and cis-4,7,10,13,16,19-docosahexaenoic acid (DHA) levels changed over time after
      sacha inchi oil ingestion but not with sunflower oil. The time at maximal
      concentration (tmax) for ALA was 2 h after sacha inchi oil ingestion. No ALA in
      plasma was observed after sunflower oil consumption. The maximal concentration of
      ALA was 2.84 +/- 0.36 mg/ml in women and 0.94 +/- 0.57 mg/ml in men, p < 0.05,
      whereas maximal concentration of DHA was 2.60 +/- 0.84 mg/ml in women and 1.00 +/
      0.38 mg/ml in men (p > 0.05). There is a trend for higher plasma ALA levels with
      15 ml sacha inchi oil. After 2 h of consumption, plasma delta triacylglycerol
      were reduced with sunflower oil but slightly increased with sacha inchi oil. A
      reduction in plasma delta triacylglycerol-rich lipoprotein cholesterol was
      observed with both oils. CONCLUSION: Consumption of sacha inchi oil increased ALA
      and DHA in plasma.

PMID- 24090041
TI  - Evolution of HIV-1 coreceptor usage and coreceptor switching during pregnancy.
AB  - Coreceptor switch from CCR5 to CXCR4 is associated with HIV disease progression.
      To document the evolution of coreceptor tropism during pregnancy, a longitudinal
      study of envelope gene sequences was performed in a group of pregnant women
      infected with HIV-1 of clade B (n=10) or non-B (n=9). Polymerase chain reaction
      (PCR) amplification of the V1-V3 region was performed on plasma viral RNA,
      followed by cloning and sequencing. Using geno2pheno and PSSMX4R5, the presence
      of X4 variants was predicted in nine of 19 subjects (X4 subjects) independent of
      HIV-1 clade. Six of nine X4 subjects exhibited CD4(+) T cell counts <200
      cells/mm(3), and the presence of X4-capable virus was confirmed using a
      recombinant phenotypic assay in four of seven cases where testing was successful.
      In five of nine X4 subjects, a statistically significant decline in the
      geno2pheno false-positive rate was observed during the course of pregnancy,
      invariably accompanied by progressive increases in the PSSMX4R5 score, the net
      charge of V3, and the relative representation of X4 sequences. Evolution toward
      X4 tropism was also echoed in the primary structure of V2, as an accumulation of
      substitutions associated with CXCR4 tropism was seen in X4 subjects. Results from
      these experiments provide the first evidence of the ongoing evolution of
      coreceptor utilization from CCR5 to CXCR4 during pregnancy in a significant
      fraction of HIV-infected women. These results inform changes in host-pathogen
      interactions that lead to a directional shaping of viral populations and viral
      tropism during pregnancy, and provide insights into the biology of HIV
      transmission from mother to child.

PMID- 24090050
TI  - Enzymatic generation of chitooligosaccharides from chitosan using soluble and
      immobilized glycosyltransferase (Branchzyme).
AB  - Chitooligosaccharides possessing remarkable biological properties can be obtained
      by enzymatic hydrolysis of chitin. In this work, the chitosanase activity of
      soluble and immobilized glycosyltransferase (Branchzyme) toward chitosan and
      biochemical characterization are described for the first time. This enzyme was
      found to be homotetrameric with a molecular weight of 256 kDa, an isoelectric
      point of 5.3, and an optimal temperature range of between 50 and 60  degrees C.
      It was covalently immobilized to glutaraldehyde-agarose with protein and activity
      immobilization yields of 67% and 17%, respectively. Immobilization improved
      enzyme stability, increasing its half-life 5-fold, and allowed enzyme reuse for
      at least 25 consecutive cycles. The chitosanase activity of Branchzyme on
      chitosan was similar for the soluble and immobilized forms. The reaction mixture
      was constituted by chitooligosaccharides with degrees of polymerization of
      between 2 and 20, with a higher concentration having degrees of polymerization of
      3-8. 

PMID- 24090049
TI  - Mortality and causes of death after traumatic spinal cord injury in Estonia.
AB  - STUDY DESIGN: Retrospective population-based study with mortality follow-up.
      OBJECTIVE: To study mortality, causes and risk factors for death in Estonian
      patients with traumatic spinal cord injury (TSCI). SETTING: All Estonian
      hospitals. METHODS: Medical records of patients with TSCI from all regional,
      central, general, and rehabilitation hospitals in Estonia from 1997 to 2007, were
      retrospectively reviewed. Mortality status was ascertained as of 31 December
      2011. Causes of death were collected from the Estonian Causes of Death Registry.
      Standardized mortality ratios (SMRs) were calculated for the entire sample and
      for causes of death. A Cox proportional hazards modeling was used to identify the
      risk indicators for death. RESULTS: During the observation period (1997-2011) 162
      patients of 595 died. Nearly half of the patients (n = 76) died during the first
      year after TSCI. The main causes of death were external causes (30%),
      cardiovascular disease (29%). and suicide (8%). The overall SMR was 2.81 (95%
      confidence interval 2.40-3.28) and SMR was higher for women than for men (3.80
      vs. 2.70). Cause-specific SMRs were markedly elevated for sepsis and suicide.
      Mortality was significantly affected by the age at the time of injury,
      neurological level, and extent of the injury as well as the year of TSCI and
      complications. CONCLUSION: Life expectancy is significantly decreased in patients
      with TSCI in Estonia compared with the general population. Deaths during the
      first year after the injury have an important impact on statistics. Treatment of
      cardiovascular diseases, infections, and prevention of suicide are useful for
      reducing mortality in patients with TSCI.

PMID- 24090051
TI  - Tuning the self-assembly of short peptides via sequence variations.
AB  - Peptide self-assembly is of direct relevance to protein science and
      bionanotechnology, but the underlying mechanism is still poorly understood. Here,
      we demonstrate the distinct roles of the noncovalent interactions and their
      impact on nanostructural templating using carefully designed hexapeptides,
      I2K2I2, I4K2, and KI4K. These simple variations in sequence led to drastic
      changes in final self-assembled structures. beta-sheet hydrogen bonding was found
      to favor the formation of one-dimensional nanostructures, such as nanofibrils
      from I4K2 and nanotubes from KI4K, but the lack of evident beta-sheet hydrogen
      bonding in the case of I2K2I2 led to no nanostructure formed. The lateral
      stacking and twisting of the beta-sheets were well-linked to the hydrophobic and
      electrostatic interactions between amino acid side chains and their interplay.
      For I4K2, the electrostatic repulsion acted to reduce the hydrophobic attraction
      between beta-sheets, leading to their limited lateral stacking and more twisting,
      and final fibrillar structures; in contrast, the repulsive force had little
      influence in the case of KI4K, resulting in wide ribbons that eventually
      developed into nanotubes. The fibrillar and tubular features were demonstrated by
      a combination of cryogenic transmission electron microscopy (cryo-TEM), negative
      stain transmission electron microscopy (TEM), and small-angle neutron scattering
      (SANS). SANS also provided structural information at shorter scale lengths. All
      atom molecular dynamics (MD) simulations were used to suggest possible molecular
      arrangements within the beta-sheets at the very early stage of self-assembly. 

PMID- 24090052
TI  - Short Communication: Defining optimality of a test for recent infection for HIV
      incidence surveillance.
AB  - The estimation of HIV incidence from cross-sectional surveys using tests for
      recent infection has attracted much interest. It is increasingly recognized that
      the lack of high performance recent infection tests is hindering the
      implementation of this surveillance approach. With growing funding opportunities,
      test developers are currently trying to fill this gap. However, there is a lack
      of consensus and clear guidance for developers on the evaluation and optimization
      of candidate tests. A fundamental shift from conventional thinking about test
      performance is needed: away from metrics relevant in typical public health
      settings where the detection of a condition in individuals is of primary interest
      (sensitivity, specificity, and predictive values) and toward metrics that are
      appropriate when estimating a population-level parameter such as incidence
      (accuracy and precision). The inappropriate use of individual-level diagnostics
      performance measures could lead to spurious assessments and suboptimal designs of
      tests for incidence estimation. In some contexts, such as population-level
      application to HIV incidence, bias of estimates is essentially negligible, and
      all that remains is the maximization of precision. The maximization of the
      precision of incidence estimates provides a completely general criterion for test
      developers to assess and optimize test designs. Summarizing the test dynamics
      into the properties relevant for incidence estimation, high precision estimates
      are obtained when (1) the mean duration of recent infection is large, and (2) the
      false-recent rate is small. The optimal trade-off between these two test
      properties will produce the highest precision, and therefore the most
      epidemiologically useful incidence estimates.

PMID- 24090053
TI  - Quantifying gait deviations in individuals with rheumatoid arthritis using the
      Gait Deviation Index.
AB  - OBJECTIVES: In this study we evaluated the usability of the Gait Deviation Index
      (GDI), an index that summarizes the amount of deviation in movement from a
      standard norm, in adults with rheumatoid arthritis (RA). The aims of the study
      were to evaluate the ability of the GDI to identify gait deviations, assess inter
      trial repeatability, and examine the relationship between the GDI and walking
      speed, physical disability, and pain. METHOD: Sixty-three adults with RA and 59
      adults with typical gait patterns were included in this retrospective case
      control study. Following a three-dimensional gait analysis (3DGA), representative
      gait cycles were selected and GDI scores calculated. To evaluate the effect of
      walking speed, GDI scores were calculated using both a free-speed and a speed
      matched reference set. Physical disability was assessed using the Health
      Assessment Questionnaire (HAQ) and subjects rated their pain during walking.
      RESULTS: Adults with RA had significantly increased gait deviations compared to
      healthy individuals, as shown by lower GDI scores [87.9 (SD = 8.7) vs. 99.4 (SD =
      8.3), p < 0.001]. This difference was also seen when adjusting for walking speed
      [91.7 (SD = 9.0) vs. 99.9 (SD = 8.6), p < 0.001]. It was estimated that a change
      of >= 5 GDI units was required to account for natural variation in gait. There
      was no evident relationship between GDI and low/high RA-related physical
      disability and pain. CONCLUSIONS: The GDI seems to useful for identifying and
      summarizing gait deviations in individuals with RA. Thus, we consider that the
      GDI provides an overall measure of gait deviation that may reflect lower
      extremity pathology and may help clinicians to understand the impact of RA on
      gait dynamics.

PMID- 24090054
TI  - CD36 enhances fatty acid uptake by increasing the rate of intracellular
      esterification but not transport across the plasma membrane.
AB  - CD36 is a multifunctional protein that enhances cellular fatty acid (FA) uptake,
      a key step in energy metabolism, and its dysregulation in multiple tissue sites
      is central to obesity-linked diabetes, a risk factor for atherosclerosis.
      Although CD36 has been implicated in FA uptake in a correlative way, the
      molecular mechanisms are not known. Their elucidation in cells is confounded by
      receptor-mediated uptake of low-density lipoprotein by CD36 and the competitive
      and/or contributive effects of other proteins involved in FA transport and
      metabolism, which include caveolin(s), fatty acid transport protein (FATP),
      intracellular fatty acid binding protein, and enzymes involved in the conversion
      of FAs to esters. Here we utilized a simpler cellular system (HEK cells), which
      lack caveolin-1, CD36, and FATP and metabolize FAs slowly compared to the time
      frame of transmembrane FA movement. Our previous studies of HEK cells showed that
      caveolin-1 affects FA binding and translocation across the plasma membrane and
      but not FA esterification [Simard, J. R., et al. (2010) J. Lipid Res. 51 (5), 914
      922]. Our key new finding is that CD36 accelerates FA uptake and extensive
      incorporation into triglycerides, a process that is slower (minutes) than
      transmembrane movement (seconds). Real-time fluorescence measurements showed that
      the rates of binding and transport of oleic acid into cells with and without CD36
      were not different. Thus, CD36 enhances intracellular metabolism, i.e.,
      esterification, and thereby increases the rate of FA uptake without catalyzing
      the translocation of FA across the plasma membrane, suggesting that CD36 is
      central to FA uptake via its effects on intracellular metabolism. 

PMID- 24090055
TI  - Patient reported outcome instruments used in clinical trials of HIV-infected
      adults on NNRTI-based therapy: a 10-year review.
AB  - BACKGROUND: Patient-reported outcomes (PROs) may provide valuable information to
      clinicians and patients when choosing initial antiretroviral therapy. OBJECTIVE:
      To identify and classify PRO instruments used to measure treatment effects in
      clinical trials evaluating NNRTIs. METHODS: We conducted a structured literature
      review using PubMed to identify NNRTI trials published from March 2003 to
      February 2013. Studies identified--based on disease, instrument, PRO, and NNRTI
      medication terms were reviewed--to identify PRO instruments. Domains measured
      within each instrument were recorded to understand key areas of interest in
      NNRTIs. RESULTS: Of 189 articles reviewed, 27 validated instruments were
      administered in 26 unique trials, with a mean of 1.9 instruments (median: 1;
      range: 1-7) per trial. The Medical Outcomes Study HIV Health Survey (MOS-HIV) was
      the most commonly used instrument (n = 8 trials). Seventeen trials (65%) included
      at least one multidimensional health-related quality of life (HRQL) instrument
      (HIV-targeted, n = 11; general, n = 8). Other validated instruments measured
      sleep (n = 5), depression (n = 5), anxiety (n = 4), psychiatric symptoms (n = 2),
      beliefs about HIV medications (n = 2), HIV symptoms (n = 1), and stress (n = 1).
      CONCLUSIONS: Although review of recent NNRTI trials suggests a lack of consensus
      on the optimal PRO instruments, a typical battery is comprised of a
      multidimensional HRQL measure coupled with one or more symptom measures. Further
      work is needed to clarify advantages and disadvantages of using specific PRO
      instruments to measure relevant constructs and to identify the most useful
      batteries of instruments for NNRTI trials.

PMID- 24090056
TI  - Mercury vapour exposure during dental student training in amalgam removal.
AB  - BACKGROUND: Amalgam that is used for dental fillings contains approximately 50%
      elemental mercury. During dental student training, amalgam is often removed by
      drilling without the use of water spray and suction, which are protective
      measures in preventing mercury aerosol. In this study we measured mercury vapor
      levels in ambient air during amalgam removal as is typically performed in dental
      training. METHODS: Mercury vapor levels in ambient air were measured in a dental
      school laboratory during removal of amalgam fillings from artificial teeth set
      into a dental jaw simulator. Mercury vapor was measured under three conditions
      (25 measurements each): with the simultaneous use of water spray and suction,
      with the use of suction only, and with the use of neither suction nor water
      spray. These three conditions are all used during dental student training.
      Results were compared to Alberta occupational exposure limits for mercury vapor
      in order to assess potential occupational risk to students. Analysis of variance
      testing was used to compare data obtained under the three conditions. RESULTS:
      When water spray and suction were used, mercury vapor levels ranged from 4.0 to
      19.0 MUg/m3 (arithmetic mean = 8.0 MUg/m3); when suction only was used, mercury
      vapor levels ranged from 14.0 to 999.0 (999.0 MUg/m3 represents the high limit
      detection of the Jerome analyzer) (arithmetic mean = 141.0 MUg/m3); when neither
      suction nor water was used, the vapor levels ranged from 34.0 to 796.0 MUg/m3
      (arithmetic mean = 214.0 MUg/m3). CONCLUSIONS: The Alberta Occupational Health
      and Safety threshold limit value for mercury vapor over an eight-hour time
      weighted period is 25.0 MUg/m3. The absolute ceiling for mercury vapor, not to be
      exceeded at any time, is 125.0 MUg/m3. When both water spray and suction were
      used, mercury vapor levels were consistently below this threshold. When suction
      without water spray was used, mercury vapor levels exceeded the safety threshold
      8% of the time. When neither water spray nor suction was used, 36% of the mercury
      vapor readings exceeded the absolute ceiling value. To maximize safety, dental
      schools should train students to remove amalgam only while using water spray and
      high volume suction. Alternatively, students should use appropriate occupational
      hygiene personal protective equipment during amalgam removals.

PMID- 24090057
TI  - The impact of loop electrosurgical excision procedure (LEEP) for CIN 2,3 on
      spontaneous preterm delivery in twin pregnancies by assisted reproductive
      technique: preliminary data.
AB  - The objective of this study was to compare the frequency of spontaneous preterm
      delivery before 35 weeks in 7 dichorionic twin pregnancies obtained after loop
      electrosurgical excision procedure (LEEP) for cervical intraepithelial neoplasia
      (CIN) 2,3 with respect to 21 twin pregnancies without previous cervical
      treatment. All the pregnancies were obtained after assisted reproduction
      techniques (ART). Same age at delivery was observed between two groups (p = 0.81)
      and none of our twin pregnancies after LEEP had a threatened preterm labor while
      four controls (19%) underwent a spontaneous preterm delivery (p = 0.35). These
      preliminary data seem to indicate that LEEP may not be responsible of spontaneous
      preterm delivery in twin pregnancies subsequent to ART.

PMID- 24090059
TI  - Electrospun polystyrene nanofiber membrane with superhydrophobicity and
      superoleophilicity for selective separation of water and low viscous oil.
AB  - The ability to prepare solid surfaces with well-controlled superhydrophobic and
      superoleophilic properties is of paramount importance to water-oil separation
      technology. Herein, we successfully prepared superhydrophobic-superoleophilic
      membranes by single-step deposition of polystyrene (PS) nanofibers onto a
      stainless steel mesh via electrospinning. The contact angles of diesel and water
      on the prepared PS nanofiber membrane were 0 degrees  and 155 degrees  +/- 3
      degrees , respectively. Applications of the PS nanofiber membrane toward
      separating liquids with low surface tension, such as oil, from water were
      investigated in detail. Gasoline, diesel, and mineral oil were tested as
      representative low-viscosity oils. The PS nanofiber membranes efficiently
      separated several liters of oil from water in a single step, of only a few
      minutes' duration. The superhydrophobic PS nanofiber membrane selectively absorbs
      oil, and is highly efficient at oil-water separation, making it a very promising
      material for oil spill remediation.

PMID- 24090060
TI  - Dual LC-MS platform for high-throughput proteome analysis.
AB  - We describe a dual-column interface for parallel chromatography to improve
      throughput during LC-MS experimentation. The system employs a high-voltage switch
      to operate two capillary column/nanospray emitters fixed at the MS orifice.
      Sequentially loading one column while operating the second nearly doubles the LC
      MS duty cycle. Given the innate run-to-run variation of a nanospray LC-MS (12%
      RSD peak area; 2% retention time), the intercolumn variability of the platform
      showed no meaningful difference for proteome analysis, with equal numbers of
      proteins and peptides identified per column. Applied to GeLC analysis of an E.
      coli extract, throughput was increased using one of three methods: doubling the
      number of replicates, increasing the LC gradient length, or sectioning the gel
      into twice as many fractions. Each method increased the total number of
      identifications as well as detection throughput (number of peptides/proteins
      identified per hour). The greatest improvement was achieved by doubling the
      number of gel slices (10 vs 5). Analysis on the dual column platform provided a
      26% increase in peptides identified per hour (24% proteins). This translates into
      ~50% more total proteins and peptides identified in the experiment using the dual
      LC-MS platform.

PMID- 24090058
TI  - Structure and dynamic behavior of Toll-like receptor 2 subfamily triggered by
      malarial glycosylphosphatidylinositols of Plasmodium falciparum.
AB  - Proinflammatory responses by Toll-like receptors (TLRs) to malaria infection are
      considered to be a significant factor in suppressing pathogen growth and in
      disease control. The key protozoan parasite Plasmodium falciparum causes malaria
      through glycosylphosphatidylinositols (GPIs), which induce the host immune
      response mainly via TLR2 signalling. Experimental studies have suggested that
      malarial GPIs from P. falciparum are recognized by the TLR2 subfamily. However,
      the interaction site and their involvement in the activation mechanism are still
      unknown. A better understanding of the detailed structure of the TLR-GPI
      interaction is important for the design of more effective anti-malarial
      therapeutics. We used a molecular docking method to predict the binding regions
      of malarial GPIs with the TLR2 subfamily members. We also employed molecular
      dynamics simulations and principal component analysis to understand ligand
      induced conformational changes of the TLR2 subfamily. We observed the expected
      structural changes upon ligand binding, and significant movements were found in
      loop regions located in the ligand-binding site of the TLR2 subfamily. We further
      propose that the binding modes of malarial GPIs are similar to lipopeptides, and
      that the lipid portions of the ligands could play an essential role in selective
      dimerization of the TLR2 subfamily. 

PMID- 24090068
TI  - Disulfonimide-catalyzed asymmetric synthesis of beta3-amino esters directly from
      N-Boc-amino sulfones.
AB  - An asymmetric Mannich reaction of silyl ketene acetals with N-Boc-amino sulfones
      has been developed. A chiral disulfonimide efficiently catalyzes both the in situ
      generation of the corresponding N-Boc imines and the asymmetric Mannich reaction
      with excellent yields and enantioselectivities. Kinetic studies confirm a
      proposed stepwise mechanism. 

PMID- 24090069
TI  - The complex relationships involved in global health: a qualitative description.
AB  - BACKGROUND: Growing numbers of medical trainees now participate in global health
      experiences (GHEs) during their training. To enhance these experiences we sought
      to explore expectations inherent in the relationships between GHE stakeholder
      groups. METHODS: 20 open-ended, semi-structured interviews probed participant
      perceptions and assumptions embedded in GHEs. A fundamental qualitative
      descriptive approach was applied, with conventional content analysis and constant
      comparison methods, to identify and refine emerging themes. Thematic structure
      was finalized when saturation was achieved. Participants all had experience as
      global health participants (10 trainees, 10 professionals) from an urban,
      academic, Canadian medical centre. RESULTS: We identified three stakeholder
      groups: participants (trainees and professionals), host communities, and
      sponsoring institutions. During interviews, four major themes emerged: (i)
      cultural challenges, (ii) expectations and perceptions, (iii) relationships and
      communication, and (iv) discordant objectives. Within each theme, participants
      recurrently described tensions existing between the three stakeholder groups.
      CONCLUSIONS: GHE participants frequently face substantial tensions with host
      communities and sponsoring agencies. Trainees are particularly vulnerable as they
      lack experience to navigate these tensions. In the design of GHEs, the needs of
      each group must be considered to ensure that benefits outweigh potential harms.
      We propose a conceptual model for developing educational objectives that
      acknowledge all three GHE stakeholder groups.

PMID- 24090070
TI  - The SseC translocon component in Salmonella enterica serovar Typhimurium is
      chaperoned by SscA.
AB  - BACKGROUND: Salmonella enterica is a causative agent of foodborne gastroenteritis
      and the systemic disease known as typhoid fever. This bacterium uses two type
      three secretion systems (T3SSs) to translocate protein effectors into host cells
      to manipulate cellular function. Salmonella pathogenicity island (SPI)-2 encodes
      a T3SS required for intracellular survival of the pathogen. Genes in SPI-2
      include apparatus components, secreted effectors and chaperones that bind to
      secreted cargo to coordinate their release from the bacterial cell. Although the
      effector repertoire secreted by the SPI-2 T3SS is large, only three virulence
      associated chaperones have been characterized. RESULTS: Here we report that SscA
      is the chaperone for the SseC translocon component. We show that SscA and SseC
      interact in bacterial cells and that deletion of sscA results in a loss of SseC
      secretion, which compromises intracellular replication and leads to a loss of
      competitive fitness in mice. CONCLUSIONS: This work completes the
      characterization of the chaperone complement within SPI-2 and identifies SscA as
      the chaperone for the SseC translocon.

PMID- 24090072
TI  - Turkish Thoracic Society 16th Annual Congress: while I breathe, I hope.
AB  - Turkish Thoracic Society Meeting Antalya, Turkey, 3-7 April 2013 This year, the
      16th Annual Congress of Turkish Thoracic Society took place in Antalya, Turkey,
      on 3-7 April 2013. The Turkish Thoracic Society has successfully organized 15
      congresses starting in 1996, but it has been held annually since 2000.
      Considerable effort, dedication and enthusiasm behind the scenes are the major
      reasons for the national success and high quality of the congress. Each national
      congress of the Turkish Thoracic Society represents an outstanding collaboration
      between headquarters and the chief committee, all the members, specialists,
      residents and sponsors. It was officially reported that this year the congress
      had attracted over 1500 participants from different parts of Turkey along with 23
      international faculties. A total of 815 abstracts have been sent to the
      scientific program committee and 153 abstracts among them have been accepted as
      oral presentations and the remaining have ended up as poster presentation. 

PMID- 24090071
TI  - Longitudinal study of respiratory function and symptoms in a non-smoking group of
      long-term officially-acknowledged victims of pollution-related illness.
AB  - BACKGROUND: Air pollution is known to be a leading cause of respiratory symptoms.
      Many cross-sectional studies reported that air pollution caused respiratory
      disease in Japanese individuals in the 1960s. Japan has laws regulating air
      pollution levels and providing compensation for victims of pollution-related
      respiratory disease. However, long-term changes in respiratory function and
      symptoms in individuals who were exposed to air pollution in the 1960s have not
      been well studied. This study aimed to investigate longitudinal respiratory
      function and symptoms in older, non-smoking, long-term officially-acknowledged
      victims of pollution-related illness. METHODS: The study included 563 officially
      acknowledged victims of pollution-related illness living in Kurashiki, Okayama
      who were aged >= 65 years in 2009. Data were retrospectively collected from
      yearly respiratory symptom questionnaires and spirometry examinations conducted
      from 2000 to 2009. RESULTS: Respiratory function declined significantly from 2000
      to 2009 (p < 0.01), but the mean annual changes were relatively small. The change
      in mean vital capacity was -40.5 ml/year in males and -32.7 ml/year in females,
      and the change in mean forced expiratory volume in 1 second was -27.6 ml/year in
      males and -23.9 ml/year in females. Dyspnea was the only symptom that worsened
      significantly from 2000 to 2009 in both sexes (males: p < 0.05, females: p <
      0.01). CONCLUSIONS: Our results suggest that the high concentrations of air
      pollutants around 1970 resulted in a decrease in respiratory function and an
      increase in respiratory symptoms in the study population. From 2000 to 2009, the
      mean annual changes in respiratory function were within the normal range, even
      though the severity of dyspnea worsened. The changes in respiratory function and
      symptoms over the study period were probably due to aging. The laws governing air
      pollution levels and providing compensation for officially-acknowledged victims
      of pollution-related illness in Japan may be effective for respiratory disease
      cause by pollution.

PMID- 24090073
TI  - The highest background radiation school in the world and the health status of its
      students and their offspring.
AB  - Although the average effective human dose from natural background radiation is
      about 2.4 mSv per year, the students of the Saeid Nafisi school in Ramsar
      received effective doses of about 250 mSv while studying there for over 5 years.
      The goal of this project was a retrospective study of the health status of former
      students of this school and their offspring. The list of the students of the
      Saeid Nafisi school (high background radiation) and Taleghani and Kashani schools
      (ordinary background radiation) was provided by the Department of Education.
      After matching sex, age and socioeconomic level and obtaining their consent, part
      1 of the specifically designed questionnaire was filled out by interview, and
      clinical examinations were recorded in part 2 of the questionnaire by a
      physician. The data were analysed using Statistical Package for the Social
      Sciences 16. Our study shows that 88.1 % of general examinations of high
      background radiation school students were normal as compared with 85.7 % for
      control group. There were no significant differences. This study is interesting
      and unique. It reveals that there is no health emergency related to these high
      radiation doses. We recommend continuing the health supervision of this
      population in the future. 

PMID- 24090074
TI  - Magnetic and spectroscopic investigation of thermally and optically driven
      valence tautomerism in thioether-bridged dinuclear cobalt-dioxolene complexes.
AB  - A series of dinuclear cobalt complexes of general formula [Co(Mentpa)(diox-S
      diox)Co(Mentpa)](PF6)2.MeOH (n = 0, 2, 3) was prepared through the synthesis of
      the bis-bidentate ligand 6,6'-((1,4
      phenylenebis(methylene))bis(sulfanediyl))bis(3,5-di-tert-butyl-benzene-1,2-diol)
      (diox-S-diox). The ancillary ligands Mentpa are obtained by the tripodal tris(2
      pyridylmethyl)amine (tpa) ligand through successive introduction of methyl groups
      into the 6 position of the pyridine moieties. As expected, the steric hindrance
      induced by this substitution modulates the redox properties of the metal
      acceptor, determining the charge distribution of the metal-dioxolene adduct at
      room temperature. Magnetic measurements and X-ray photoelectron and X-ray
      absorption spectroscopies indicate that the charge distributions low-spin-Co(III)
      catecholate and high-spin-Co(II)-semiquinonate characterize the complexes formed
      by the tpa and Me3tpa tetradentate ligands, respectively. The complex formed by
      the Me2tpa ligand undergoes a thermal- and light-induced interconversion of the
      two states, in agreement with the existence of a valence tautomeric equilibrium.
      All complexes were stable and behaved reproducibly under X-ray irradiation. This
      work points out a fast and simple chemical approach to structurally and
      electronically modify the catechol ring while leaving its coordination
      capabilities unaffected. These findings afford a robust chemical method to
      prepare sulfur-functionalized dioxolene ligands as new molecular bricks for
      chemical functionalization of noble metal surfaces with this class of molecular
      switches. 

PMID- 24090075
TI  - Selection of recombinant antibodies by phage display technology and application
      for detection of allergenic Brazil nut (Bertholletia excelsa) in processed foods.
AB  - Current immunological methods for detection of Brazil nut allergens in foods are
      based on polyclonal antibodies raised in animals. Phage display technology allows
      the procurement of high-affinity antibodies avoiding animal immunization steps
      and therefore attaining the principle of replacement supported by animal welfare
      guidelines. In this study, we screened Tomlinson I and J libraries for specific
      binders against Brazil nut by employing a Brazil nut protein extract and a
      purified Brazil nut 2S globulin, and we successfully isolated a phage single
      chain variable fragment (named BE95) that specifically recognizes Brazil nut
      proteins. The selected phage scFv was further used as affinity probe to develop
      an indirect phage-ELISA for detection of Brazil nut in experimental binary
      mixtures and in commercial food products, with a limit of detection of 5 mg g(
      1). This study describes for the first time the isolation of recombinant antibody
      fragments specific for an allergenic tree nut protein from a naive library and
      paves the way to develop new immunoassays for food analysis based on probes that
      can be produced in vitro when required and do not rely on animal immunization.

PMID- 24090076
TI  - Cardiac arrhythmias associated with spinal cord injury.
AB  - CONTEXT/OBJECTIVES: To review the current literature to reveal the incidence of
      cardiac arrhythmias and its relation to spinal cord injury (SCI). METHODS:  DATA
      SOURCE: MEDLINE database, 304 hits, and 32 articles were found to be relevant.
      The relevant articles all met the inclusion criteria: (1) contained original data
      (2) on cardiac arrhythmias (3) in humans with (4) traumatic SCI. RESULTS: In the
      acute phase of SCI (1-14 days after injury) more cranial as well as more severe
      injuries seemed to increase the incidence of bradycardia. Articles not covering
      the first 14 days after injury, thus describing the chronic phase of SCI, showed
      that individuals with SCI did not have a higher incidence of cardiac arrhythmias
      compared with able-bodied controls. Furthermore, their heart rate did not differ
      significantly. Penile vibro-stimulation was the procedure investigated most
      likely to cause bradycardia, which in turn was associated with episodes of
      autonomic dysreflexia. The incidence of bradycardia was found to be 17-77% for
      individuals with cervical SCI. For individuals with thoracolumbar SCI, the
      incidence was 0-13%. CONCLUSION: Bradycardia was commonly seen in the acute stage
      after SCI as well as during procedures such as penile vibro-stimulation and
      tracheal suction. These episodes of bradycardia were seen more often in
      individuals with cervical injuries. Longitudinal studies with continuous
      electrocardiogram recordings are needed to uncover the true relation between
      cardiac arrhythmias and SCI.

PMID- 24090077
TI  - Physiological and pharmacokinetic effects of oral 1,3-dimethylamylamine
      administration in men.
AB  - BACKGROUND: 1,3-dimethylamylamine (DMAA) has been a component of dietary
      supplements and is also used within "party pills," often in conjunction with
      alcohol and other drugs. Ingestion of higher than recommended doses results in
      untoward effects including cerebral hemorrhage. To our knowledge, no studies have
      been conducted to determine both the pharmacokinetic profile and physiologic
      responses of DMAA. METHODS: Eight men reported to the lab in the morning
      following an overnight fast and received a single 25 mg oral dose of DMAA. Blood
      samples were collected before and through 24 hours post-DMAA ingestion and
      analyzed for plasma DMAA concentration using high-performance liquid
      chromatography-mass spectrometry. Resting heart rate, blood pressure, and body
      temperature was also measured. RESULTS: One subject was excluded from the data
      analysis due to abnormal DMAA levels. Analysis of the remaining seven
      participants showed DMAA had an oral clearance of 20.02 +/- 5 L?hr-1, an oral
      volume of distribution of 236 +/- 38 L, and terminal half-life of 8.45 +/- 1.9
      hr. Lag time, the delay in appearance of DMAA in the circulation following
      extravascular administration, varied among participants but averaged
      approximately 8 minutes (0.14 +/- 0.13 hr). The peak DMAA concentration for all
      subjects was observed within 3-5 hours following ingestion and was very similar
      across subjects, with a mean of ~70 ng?mL-1. Heart rate, blood pressure, and body
      temperature were largely unaffected by DMAA treatment. CONCLUSIONS: These are the
      first data to characterize the oral pharmacokinetic profile of DMAA. These
      findings indicate a consistent pattern of increase across subjects with regards
      to peak DMAA concentration, with peak values approximately 15-30 times lower than
      those reported in case studies linking DMAA intake with adverse events. Finally,
      a single 25 mg dose of DMAA does not meaningfully impact resting heart rate,
      blood pressure, or body temperature. TRIAL REGISTRATION: NCT01765933.

PMID- 24090078
TI  - A new switching device for printed electronics: inkjet-printed
      microelectromechanical relay.
AB  - Printed electronics employing solution-processed materials is considered to be
      the key to realizing low-cost large-area electronic systems, but the performance
      of printed transistors is generally inadequate for most of the intended
      applications due to limited performance of printable semiconductor materials. We
      propose an alternative approach for a printed switch, where the use of
      semiconductors can be avoided by building mechanical switches with printed metal
      nanoparticle-based inks. In this work, we detail the first demonstration of
      inkjet-printed microelectromechanical (MEM) switches with abrupt switching
      characteristics, very low on-state resistance (~10 Omega), and very low off-state
      leakage. The devices are fabricated using a novel process scheme to build three
      dimensional cantilever structures from solution-processed metallic nanoparticles
      and sacrificial polymer layers. These printed MEM switches thus represent a
      uniquely attractive path for realizing printed electronics.

PMID- 24090079
TI  - Scope of Western surgical techniques to correct cleft lip and palate prior to the
      18th century.
AB  - OBJECTIVES: To present the state of knowledge and surgical practice concerning
      cleft lip and palate leading to the modern era. DESIGN: Bibliographical review.
      SETTING: Analysis of the scientific medical, surgical, and odontological
      literature from the 16th to 18th centuries. RESULTS: Texts and art confirm the
      existence of cleft lip and palate from antiquity in all cultures; however, the
      first certain references in Western scientific literature did not appear until
      the works of Celsus (ca. 25 BC to AD 50) and Galen (AD 129 to 200). Indications
      for cleft lip surgery appear in the Middle Ages with Albucasis (936 to 1013) and
      Yperman (1260 to 1332). From the Renaissance period onward, and with the
      invention of the printing press, numerous authors described their own surgical
      methods. CONCLUSIONS: Given the limitations imposed by pain and infection, the
      authors of the Modern Age focus on correcting the functional and esthetic defect
      of the lip with techniques that do not differ greatly from those described in the
      Middle Ages. The treatment for cleft palate was limited to the creation of
      "obturators" and surgery for cleft palate was not possible until the 19th
      century.

PMID- 24090080
TI  - Self-care among caregivers of people living with HIV and AIDS in Kakola location,
      Nyando District, Kisumu County, Kenya.
AB  - This study was carried out in Kakola Location of Nyando District in Kenya. The
      aim of study was to determine the factors influencing the practice of self-care
      among caregivers for person living with HIV/AIDS (PLWHAs) as well as their
      practice of self-care. A study by World Health Organization approximated that in
      developing countries, the need for long-term care will increase by as much as 40%
      in the coming years. HIV/AIDS has been cited as one of the challenges in long
      term care. As demand for long-term care increases, the assumption that extended
      family networks can meet all the needs of their members deteriorates. The
      community-based survey employed descriptive cross-sectional design, involving
      primary caregivers of PLWHAs in Kakola location who had practiced care giving for
      more than 3 months. A household survey was conducted with 150 respondents.
      Quantitative data were analyzed using the Statistical Package for Social Sciences
      (SPSS) program version 11.0. Simple frequencies and cross tabulations to compare
      variables were produced. Microsoft Excel was used to produce tables and graphs.
      Majority of the respondents 124 (82.7%) were female, while 26 (17.3%) were male.
      Self-care elements most practiced by the respondents in all the age categories
      were infection prevention and nutritional care. Female respondents had the
      highest proportions in all the practices of self-care. The results also showed
      that gender, relationship of patient to caregiver and marital status were the
      main demographic factors that significantly influenced the practice of self-care
      among caregivers. There was a significant relationship between main sources of
      income of caregivers with the practice of self-care. The study also revealed that
      respondents with no education had the lowest number of respondents practicing all
      the six practices of self-care and belonging to a support group. Recommendations
      for the study included, forging partnerships among stakeholders, training of
      caregivers and review of the home-based care policy. 

PMID- 24090081
TI  - Broad and potent cellular and humoral immune responses after a second late HIV
      modified vaccinia virus ankara vaccination in HIV-DNA-primed and HIV-modified
      vaccinia virus Ankara-boosted Swedish vaccinees.
AB  - We have previously shown that an HIV vaccine regimen including three HIV-DNA
      immunizations and a single HIV-modified vaccinia virus Ankara (MVA) boost was
      safe and highly immunogenic in Swedish volunteers. A median 38 months after the
      first HIV-MVA vaccination, 24 volunteers received 10(8) plaque-forming units of
      HIV-MVA. The vaccine was well tolerated. Two weeks after this HIV-MVA
      vaccination, 18 (82%) of 22 evaluable vaccinees were interferon (IFN)-gamma
      enzyme-linked immunospot (ELISpot) reactive: 18 to Gag and 10 (45%) to Env. A
      median minimal epitope count of 4 to Gag or Env was found in a subset of 10
      vaccinees. Intracellular cytokine staining revealed CD4(+) and/or CD8(+) T cell
      responses in 23 (95%) of 24 vaccinees, 19 to Gag and 19 to Env. The frequency of
      HIV-specific CD4(+) and CD8(+) T cell responses was equally high (75%). A high
      proportion of CD4(+) and CD8(+) T cell responses to Gag was polyfunctional with
      production of three or more cytokines (40% and 60%, respectively). Of the Env
      specific CD4(+) T cells 40% were polyfunctional. Strong lymphoproliferative
      responses to Aldrithiol-2 (AT-2)-treated subtype A, B, C, and A_E virus were
      demonstrable in 21 (95%) of 22 vaccinees. All vaccinees developed binding
      antibodies to Env and Gag. Neutralizing antibodies were detected in a peripheral
      blood mononuclear cell (PBMC)-based assay against subtype B and CRF01_AE viruses.
      The neutralizing antibody response rates were influenced by the vaccine dose
      and/or mode of delivery used at the previous HIV-MVA vaccination. Thus, a second
      late HIV-MVA boost induced strong and broad cellular immune responses and
      improved antibody responses. The data support further exploration of this vaccine
      concept.

PMID- 24090082
TI  - Relationship between nutritional status and mortality during the first 2 weeks
      following treatment for cervical spinal cord injury.
AB  - BACKGROUND: The effects of nutrition on the mortality of cervical spinal cord
      injury (CSCI) patients, unlike other risk factors, are poorly documented.
      Objective The relationship between dynamic nutritional status change and
      mortality in patients treated for CSCI was investigated. METHODS: A retrospective
      study of 128 patients treated for CSCI at the Beijing Army General Hospital was
      conducted between March 2006 and March 2011. Age, spinal segment damage (C1-C4
      and C5-C7), American Spinal Injury Association (ASIA) grade, hospitalization
      duration, ventilatory support, and serum protein levels (total protein, serum
      albumin, and serum prealbumin) were assessed during early-stage treatment (<14
      days). Survival (n = 109) and death (n = 19) groups were assigned by final
      disposition of acute hospitalization. RESULTS: The survival group evidenced no
      significant changes in total protein levels during early-stage treatment,
      although these values decreased in the death group. Serum prealbumin and albumin
      levels significantly declined by treatment day 1 and throughout treatment (P <
      0.05). By days 3-5 and thereafter, significantly lower serum proteins were
      observed in the death group compared to the survival group (P < 0.05). Multiple
      segment damage, elevated ASIA, and longer ventilatory support duration were more
      prevalent in the death group (P < 0.001) CONCLUSIONS: Lower serum protein levels
      associated with hypoproteinemia and malnutrition are significant indicators of
      mortality in patients with CSCI, along with higher levels of lesions, elevated
      ASIA grades, and longer ventilatory support durations. Early corrective action
      for hypoalbuminemia may help to reduce mortality in patients with CSCI.

PMID- 24090083
TI  - Predictors of weight loss after an intensive lifestyle intervention program in
      obese patients: a 1-year prospective cohort study.
AB  - BACKGROUND: Studies of lifestyle intervention programs in morbid obesity report
      large variations in weight loss outcomes. This is reported not only between but
      also within standardized programs. Such reports point to participants'
      characteristics as possible predictors of this outcome. The aim of this
      prospective cohort study was to identify predictors of weight loss after a 1-year
      partly residential intensive lifestyle intervention program (ILI). METHODS:
      Morbidly obese patients (n=199), all Caucasian, 71% women, mean (SD) age 45.2
      (11.1) years, body mass index (BMI) 42.0 (6.2) kg/m(2), and excess body weight
      (>BMI=25 kg/m(2)) 49.4 (19.6) kg, were referred from public hospitals to a
      rehabilitation center and enrolled consecutively. The 1-year ILI comprised of
      four (n=104) or five (n=95) stays at the rehabilitation center. In both cases
      there was one main stay for 4 weeks and the remaining stays lasted 1 week each.
      In the home periods the patients were followed up by telephone and by their
      general practitioners (GP). The patients were also encouraged to use a predefined
      paper based diary. Health related quality of life (HRQL), diagnostic,
      anthropometric, socio-demographic, psychosocial and intervention characteristics
      were measured at baseline, 12 weeks and 1 year. Multiple linear regression
      analyses were performed to extract possible predictors of weight loss at 1-year.
      Direct and indirect effects of these predictors were tested through structural
      equation modeling. RESULTS: The mean (SD) 1-year weight loss was 10 (11) kg,
      corresponding to an 8 (8) % reduction of body weight from baseline. Mean excess
      weight loss (EWL) was 20 (22) % ranging from 104% to -77%. The adherence to a
      diary (r=.16), type 2 diabetes (r=-.14) and frequency of GP-visits (r=.23) were
      significantly associated with EWL at 12 weeks. Predictors of 1-year EWL were 12
      week EWL (r=.66), occupational status (r=.11), age (r=.19), and mental HRQL (r=
      .16), all p<.05. The path model explained 50% of the variation (r(2)=.50) of 1
      year EWL. CONCLUSION: Larger 12 week weight loss, being employed, lower mental
      HRQL and being older predicts larger weight loss after 1 year in morbidly obese
      patients following ILI. Not having type 2 diabetes, using a diary combined with
      regular GP follow-up influence the 12-week weight loss. TRIAL REGISTRATION:
      Clinicaltrials.gov: NCT00477399.

PMID- 24090084
TI  - Site-specific glycan-peptide analysis for determination of N-glycoproteome
      heterogeneity.
AB  - A combined glycomics and glycoproteomics strategy was developed for the site
      specific analysis of N-linked glycosylation heterogeneity from a complex
      mammalian protein mixture. Initially, global characterization of the N-glycome
      was performed using porous graphitized carbon liquid chromatography-tandem mass
      spectrometry (PGC-LC-MS/MS) and the data used to create an N-glycan modification
      database. In the next step, tryptic glycopeptides were enriched using
      zwitterionic hydrophilic interaction liquid chromatography (Zic-HILIC) and
      fractionated by reversed-phase liquid chromatography (RPLC; pH 7.9). The
      resulting fractions were each separated into two equal aliquots. The first set of
      aliquots were treated with peptide-N-glycosidase F (PNGase F) to remove N-glycans
      and the former N-glycopeptides analyzed by nano-RPLC-MS/MS (pH 2.7) and
      identified by Mascot database search. This enabled the creation of a glycopeptide
      centric concatenated database for each fraction. The second set of aliquots was
      analyzed directly by nanoRPLC-MS/MS (pH 2.7), employing fragmentation by CID and
      HCD. The assignment of glycan compositions to peptide sequences was achieved by
      searching the N-glycopeptide HCD MS/MS spectra against the glycopeptide-centric
      concatenated databases employing the N-glycan modification database. CID spectra
      were used to assign glycan structures identified in the glycomic analysis to
      peptide sequences. This multidimensional approach allowed confident
      identification of 863 unique intact N-linked glycopeptides from 161 rat brain
      glycoproteins. 

PMID- 24090085
TI  - Relative photooxidation and photoreduction activities of the {100}, {101}, and
      {001} surfaces of anatase TiO2.
AB  - The photoredox ability of the TiO2 {100}, {101}, and {001} surfaces is
      investigated by examining the trapping energies, trapping sites, and relative
      oxidation and reduction potentials of simulated photogenerated holes and
      electrons in the form of more realistic polaronic states on the basis of density
      functional electronic structure calculations. Our results enable us to re
      estimate their relative photooxidation ({100} > {101} > {001}) and photoreduction
      ({100} > {101} > {001}) activities, which rectify the conventional understanding.
      The dual functions of the surface under coordinated atoms acting as active
      adsorption sites for adsorbates and hindering the population of electrons to the
      outermost surface layer are identified, and the specific surface geometric
      structures also play an important role in trapping holes and electrons through
      the ease of lattice distortion. In addition, we attribute the commonly low
      photocatalytic performance of the {101} surface to the large and similar trapping
      energies and adjacent trapping sites for electrons and holes, which result in
      high electron-hole recombination rates. However, the large difference in trapping
      energies for electrons and holes on different surfaces allows us to spatially
      gather electrons and holes on different surfaces by artificially designing the
      exposing facets of nanocrystals without resorting to the energy band potential
      difference between surfaces, thus expanding the ideas to improve the
      photocatalytic properties of materials through the regulation of crystal facets.
      Our present work can provide a helpful message for the design of more reactive
      photocatalytic TiO2 nanocrystals and the fabrication of other reactive
      photocatalysts. 

PMID- 24090086
TI  - Digital dermatitis in cattle is associated with an excessive innate immune
      response triggered by the keratinocytes.
AB  - BACKGROUND: Digital Dermatitis (DD) is a common disease of dairy cows, the
      pathogenesis of which is still not clear. This study examined some host responses
      associated with the typical lesions, in an attempt to further elucidate the
      pathogenesis of the disease. Twenty four samples representing the 5 different
      clinical stages of DD (M0-M4) were collected from slaughtered cattle for
      histopathological and immunological analyses. RESULTS: Significant increases in
      total epidermal thickness were found in M2, M3, and M4 when compared with M0 and
      M1. M3 samples, when compared with M0 and M1, were characterized by a significant
      increase in the thickness of the keratin layer. Counts of both eosinophils and
      neutrophils were at a maximum in the M2 stage and decreased in the M3 and M4
      stage. A significant increase in IL8 expression was observed in the M2-M3 stages
      of the disease and immunohistochemical staining showed the source as
      keratinocytes, suggesting an important role for keratinocyte-derived IL8 in the
      pathogenesis of DD. CONCLUSION: Results of the present study point to a strong
      stimulation of the innate immune response at the level of the keratinocytes
      throughout most of the clinical stages, and a delayed response of the adaptive
      immune reaction.

PMID- 24090087
TI  - Potential of recombinant inorganic pyrophosphatase antigen as a new vaccine
      candidate against Baylisascaris schroederi in mice.
AB  - The intestinal nematode Baylisascaris schroederi is an important cause of death
      for wild and captive giant pandas. Inorganic pyrophosphatases (PPases) are
      critical for development and molting in nematode parasites and represent
      potential targets for vaccination. Here, a new PPase homologue, Bsc-PYP-1, from
      B. schroederi was identified and characterized, and its potential as a vaccine
      candidate was evaluated in a mouse challenge model. Sequence alignment of PPases
      from nematode parasites and other organisms show that Bsc-PYP-1 is a nematode
      specific member of the family I soluble PPases. Immunohistochemistry revealed
      strong localization of native Bsc-PYP-1 to the body wall, gut epithelium, ovary
      and uterus of adult female worms. Additionally, Bsc-PYP-1 homologues were found
      in roundworms infecting humans (Ascaris lumbricoides), swine (Ascaris suum) and
      dogs (Toxocara canis). In two vaccine trials, recombinant Bsc-PYP-1 (rBsc-PYP-1)
      formulated with Freund complete adjuvant induced significantly high antigen
      specific immunoglobulin (Ig)G but no IgE or IgM responses. Analysis of IgG
      subclass profiles revealed a greater increase of IgG1 than IgG2a. Splenocytes
      from rBsc-PYP-1/FCA-immunized mice secreted low levels of T helper (Th)1-type
      cytokines, interferon-gamma and interleukin (IL)-2, while producing significantly
      high levels of IL-10 and significantly elevated levels of IL-4 (Th2 cytokines)
      after stimulation with rBsc-PYP-1 in vitro. Finally, vaccinated mice had 69.02
      71.15% reductions (in 2 experiments) in larval recovery 7 days post-challenge
      (dpc) and 80% survival at 80 dpc. These results suggest that Th2-mediated
      immunity elicited by rBsc-PYP-1 provides protection against B. schroederi, and
      the findings should contribute to further development of Bsc-PYP-1 as a candidate
      vaccine against baylisascariasis.

PMID- 24090090
TI  - Alterations of natriuretic peptides amino-terminal pro B-type natriuretic peptide
      and amino-terminal pro C-type natriuretic peptide during the pregnancy.
AB  - OBJECTIVE: The aim of this study was to determine the plasma levels of
      natriuretic peptides amino-terminal pro B-type natriuretic peptide (NT proBNP)
      and amino-terminal pro C-type natriuretic peptide (NT proCNP) during pregnancy
      and any possible changes occurring in each trimester. METHODS: This was a
      prospective longitudinal case-control study conducted in a University Hospital
      antenatal outpatient clinic. Subjects were all healthy pregnant women without a
      history of previous cardiac disease, hypertension or preeclampsia, and each
      patient was assessed during every trimester, and blood samples were collected for
      the measurement of NT proBNP and NT proCNP levels. RESULTS: Twenty pregnant women
      were followed-up during pregnancy without any complications. We obtained
      longitudinal levels of natriuretic peptides in each trimester. The mean NT proBNP
      levels were 14.95 +/- 16.8, 9.37 +/- 10.76, 52.48 +/- 126.65 pmol/ml and the mean
      NT proCNP levels were 44.64 +/- 41.64, 45.70 +/- 47.03, 47.22 +/- 55.09 pmol/l,
      respectively. No statistically significant alteration of plasma levels of
      natriuretic peptides was detected between trimesters. CONCLUSION: This is the
      first study evaluating the longitudinal levels of NT proCNP during the pregnancy,
      and demonstrates that NT proCNP remained constant, but NT proBNP levels do not
      significantly alter during pregnancy.

PMID- 24090091
TI  - Exploring structures and energetics of large OCS clusters by correlated methods.
AB  - An extensive minima search based on accurate estimation of binding energies in
      (OCS)n clusters for n = 2-5 is carried out employing MP2 and CCSD(T) levels of
      theory. Features of the molecular electrostatic potential of the OCS monomer are
      utilized for building the laterally shifted and linear aggregates of OCS. Trial
      structures generated through cluster building algorithm are subjected to geometry
      optimization at MP2 level using aug-cc-pvTZ (TZ) basis set. Molecular tailoring
      approach (MTA)-based single-point energies at MP2/QZ and CCSD(T)/TZ levels are
      calculated for the estimation of binding energy at complete basis set (CBS)
      limit. For a comparative study, benchmark calculations employing the dispersion
      corrected B2PLYPD functional with TZ basis set are effected. The resulting
      geometrical parameters from which are found to be in excellent agreement with the
      experimental findings. With increasing cluster size, the calculated vibrational
      frequency at the MP2/DZ level of theory shows a substantial blue shift for the
      asymmetric C-O stretch. The results from the present study clearly bring out the
      feasibility of carrying out ab initio calculations on large-sized clusters on
      limited hardware with a minimal loss of accuracy. 

PMID- 24090088
TI  - Bridging defects in chronic spinal cord injury using peripheral nerve grafts
      combined with a chitosan-laminin scaffold and enhancing regeneration through them
      by co-transplantation with bone-marrow-derived mesenchymal stem cells: case
      series of 14 patients.
AB  - OBJECTIVE: To investigate the effect of bridging defects in chronic spinal cord
      injury using peripheral nerve grafts combined with a chitosan-laminin scaffold
      and enhancing regeneration through them by co-transplantation with bone-marrow
      derived mesenchymal stem cells. METHODS: In 14 patients with chronic paraplegia
      caused by spinal cord injury, cord defects were grafted and stem cells injected
      into the whole construct and contained using a chitosan-laminin paste. Patients
      were evaluated using the International Standards for Classification of Spinal
      Cord Injuries. RESULTS: Chitosan disintegration leading to post-operative seroma
      formation was a complication. Motor level improved four levels in 2 cases and two
      levels in 12 cases. Sensory-level improved six levels in two cases, five levels
      in five cases, four levels in three cases, and three levels in four cases. A four
      level neurological improvement was recorded in 2 cases and a two-level
      neurological improvement occurred in 12 cases. The American Spinal Impairment
      Association (ASIA) impairment scale improved from A to C in 12 cases and from A
      to B in 2 cases. Although motor power improvement was recorded in the abdominal
      muscles (2 grades), hip flexors (3 grades), hip adductors (3 grades), knee
      extensors (2-3 grades), ankle dorsiflexors (1-2 grades), long toe extensors (1-2
      grades), and plantar flexors (0-2 grades), this improvement was too low to enable
      them to stand erect and hold their knees extended while walking unaided.
      CONCLUSION: Mesenchymal stem cell-derived neural stem cell-like cell
      transplantation enhances recovery in chronic spinal cord injuries with defects
      bridged by sural nerve grafts combined with a chitosan-laminin scaffold.

PMID- 24090093
TI  - Spatial distribution of radioisotope concentrations in the offshore water and
      sediment of the Bay of Bengal (Indian Ocean), Bangladesh.
AB  - Concentrations of natural and fall-out radionuclides in the offshore seawater and
      sediment from some parts of the Bay of Bengal, Bangladesh, were determined using
      a coaxial germanium detector. The average activities of (238)U, (232)Th, (40)K
      and (137)Cs were recorded as 31.2+/-5.8, 51.9+/-9.4, 686.4+/-170.5 and 0.5+/-0.6
      Bq kg(-1) dry weight, respectively, for sediment, and 4.8+/-1.2, 5.4+/-1.2 and
      39.1+/-8.6 Bq L(-1) for (238)U, (232)Th and (40)K, respectively, in seawater. The
      concentration of (137)Cs in seawater was below the detection limit. The
      concentration of sediment (238)U was found to be positively correlated with
      (232)Th ([Formula: see text], p<0.05) and (40)K (r=0.96, p<0.01), while (232)Th
      was positively correlated with (40)K (r=0.91, p<0.05). In sediment, the
      concentration of (238)U was negatively correlated (r=-0.86, p<0.05) with sea
      depth. In the seawater sample, the only significant relationship found was
      between concentration of (232)Th and water depth (r=-0.86, p<0.05). One-factor
      analysis of variance (ANOVA) showed that the level of radioisotope concentrations
      of seawater and sediment was highly significant for (238)U (F=122, df=11,
      p=0.01), (232)Th (F=143, df=11, p=0.01) and (40)K (F=86, df=11, p=0.01). The
      results showed that the level of radioactivity decreased from coast to open sea.
      Imminent threat due to radioactivity was not observed in these parts of the Bay
      of Bengal. 

PMID- 24090094
TI  - Extremely sensitive and selective NO probe based on villi-like WO3 nanostructures
      for application to exhaled breath analyzers.
AB  - Self-assembled WO3 thin film nanostructures with 1-dimensional villi-like
      nanofingers (VLNF) have been synthesized on the SiO2/Si substrate with Pt
      interdigitated electrodes using glancing angle deposition (GAD). Room-temperature
      deposition of WO3 by GAD resulted in anisotropic nanostructures with large aspect
      ratio and porosity having a relative surface area, which is about 32 times larger
      than that of a plain WO3 film. A WO3 VLNF sensor shows extremely high response to
      nitric oxide (NO) at 200  degrees C in 80% of relative humidity atmosphere, while
      responses of the sensor to ethanol, acetone, ammonia, and carbon monoxide are
      negligible. Such high sensitivity and selectivity to NO are attributed to the
      highly efficient modualtion of potential barriers at narrow necks between
      individual WO3 VLNF and the intrinsically high sensitivity of WO3 to NO. The
      theoretical detection limit of the sensor for NO is expected to be as low as 88
      parts per trillion (ppt). Since NO is an approved biomarker of chronic airway
      inflammation in asthma, unprecedentedly high response and selectivity, and ppt
      level detection limit to NO under highly humid environment demonstrate the great
      potential of the WO3 VLNF for use in high performance breath analyzers. 

PMID- 24090097
TI  - Exploration of pathways related to the decline in female circumcision in Egypt.
AB  - BACKGROUND: There has been a large decline in female genital circumcision (FGC)
      in Egypt in recent decades. Understanding how this change has occurred so rapidly
      has been an area of particular interest to policymakers and public health
      officials alike who seek to further discourage the practice elsewhere. METHODS:
      We document the trends in this decline in the newest cohorts of young girls and
      explore the influences of three pathways--socioeconomic development, social media
      messages, and women's empowerment--for explaining the observed trends. Using the
      2005 and 2008 Egypt Demographic and Health Surveys, we estimate several logistic
      regression models to (1) examine individual and household determinants of
      circumcision, (2) assess the contributions of different pathways through which
      these changes may have occurred, and (3) assess the robustness of different
      pathways when unobserved community differences are taken into account. RESULTS:
      Across all communities, socioeconomic status, social media messages, and women's
      empowerment all have significant independent effects on the risk of circumcision.
      However, after accounting for unobserved differences across communities, only
      mother's education and household wealth significantly predict circumcision
      outcomes. Additional analyses of maternal education suggest that increases in
      women's education may be causally related to the reduction in FGC prevalence.
      CONCLUSIONS: Women's empowerment and social media appear to be more important in
      explaining differences across communities; within communities, socioeconomic
      status is a key driver of girls' circumcision risk. Further investigation of
      community-level women's educational attainment for mothers suggests that
      investments made in female education a generation ago may have had echo effects
      on girls' FGC risk a generation later.

PMID- 24090092
TI  - Perinatal factors in neonatal and pediatric lung diseases.
AB  - Wheezing and asthma are significant clinical problems for infants and young
      children, particularly following premature birth. Recurrent wheezing in infants
      can progress to persistent asthma. As in adults, altered airway structure
      (remodeling) and function (increased bronchoconstriction) are also important in
      neonatal and pediatric airway diseases. Accumulating evidence suggests that
      airway disease in children is influenced by perinatal factors including
      perturbations in normal fetal lung development, postnatal interventions in the
      intensive care unit (ICU) and environmental and other insults in the neonatal
      period. Here, in addition to genetics, maternal health, environmental processes,
      innate immunity and impaired lung development/function can all influence
      pathogenesis of airway disease in children. We summarize current understanding of
      how prenatal and postnatal factors can contribute to development of airway
      diseases in neonates and children. Understanding these mechanisms will help
      identify and develop novel therapies for childhood airway diseases. 

PMID- 24090098
TI  - Aerobic exercise increases hippocampal volume and improves memory in multiple
      sclerosis: preliminary findings.
AB  - Multiple sclerosis leads to prominent hippocampal atrophy, which is linked to
      memory deficits. Indeed, 50% of multiple sclerosis patients suffer memory
      impairment, with negative consequences for quality of life. There are currently
      no effective memory treatments for multiple sclerosis either pharmacological or
      behavioral. Aerobic exercise improves memory and promotes hippocampal
      neurogenesis in nonhuman animals. Here, we investigate the benefits of aerobic
      exercise in memory-impaired multiple sclerosis patients. Pilot data were
      collected from two ambulatory, memory-impaired multiple sclerosis participants
      randomized to non-aerobic (stretching) and aerobic (stationary cycling)
      conditions. The following baseline/follow-up measurements were taken: high
      resolution MRI (neuroanatomical volumes), fMRI (functional connectivity), and
      memory assessment. Intervention was 30-minute sessions 3 times per week for 3
      months. Aerobic exercise resulted in 16.5% increase in hippocampal volume and
      53.7% increase in memory, as well as increased hippocampal resting-state
      functional connectivity. Improvements were specific, with no comparable changes
      in overall cerebral gray matter (+2.4%), non-hippocampal deep gray matter
      structures (thalamus, caudate: -4.0%), or in non-memory cognitive functioning
      (executive functions, processing speed, working memory: changes ranged from -11%
      to +4%). Non-aerobic exercise resulted in relatively no change in hippocampal
      volume (2.8%) or memory (0.0%), and no changes in hippocampal functional
      connectivity. This is the first evidence for aerobic exercise to increase
      hippocampal volume and connectivity and improve memory in multiple sclerosis.
      Aerobic exercise represents a cost-effective, widely available, natural, and self
      administered treatment with no adverse side effects that may be the first
      effective memory treatment for multiple sclerosis patients. 

PMID- 24090099
TI  - Palladium-catalyzed sp2 and sp3 C-H bond activation and addition to isatin toward
      3-hydroxy-2-oxindoles.
AB  - The first Pd(II)-catalyzed C-H addition to isatins by direct sp(2)/sp(3) C-H bond
      activation for the construction of 3-substituted-3-hydroxy-2-oxindoles is
      reported. The bidentate nitrogen ligands were found to promote this reaction.
      Specifically, the preliminary bioassay indicated that 3-(5-chlorobenzoxazole)-3
      hydroxy-N-benzyl-2-oxindole (2w) is a new inhibitor of human kidney cancer and
      hepatocellular carcinoma cells. Moreover, this reaction system exhibits great
      functional group tolerance and requires no directing group, extra base, or
      additives. 

PMID- 24090100
TI  - Do children orphaned by AIDS experience distress over time? A latent growth curve
      analysis of depressive symptoms.
AB  - This longitudinal study aimed to examine the enduring effects of parental
      HIV/AIDS on children's psychological well-being in Asia. A sample of 1625
      children aged from 6 to 18 years old were assessed annually for their depressive
      symptoms over three years. Latent growth curve modeling (LGCM) was used to
      examine the trajectories of depressive symptoms among AIDS orphans and vulnerable
      children in comparison with children from HIV-free families. AIDS orphans
      demonstrated the highest initial level of depressive symptoms among the three
      groups. On average, children's depressive symptoms' scores can be expected to
      realize an approximate 25% decrease for AIDS orphans, 19% decrease for vulnerable
      children, and 15% decrease for comparison children over a three-year period.
      Individual differences within the groups showed that children with higher initial
      level of depressive symptoms can be expected to decrease slower over time.
      Multiple group LGCM showed that the three groups of children demonstrated
      significantly different trajectories of depressive symptoms. Among the key
      demographic factors, only age exerted an effect on the trajectory of depressive
      symptoms of vulnerable children, indicating that the younger children showed
      higher level of initial depressive symptoms and lower rate of decrease than the
      older children. The current study enriched our knowledge on the longitudinal
      effect of parental HIV/AIDS on children's emotional distress. Future
      psychological support might take the children's developmental stages and cultural
      appropriateness into consideration and deliver service for the most vulnerable
      group of children affected by HIV/AIDS. 

PMID- 24090102
TI  - Increased risk of pneumonia and bronchiolitis after bacterial colonization of the
      airways as neonates.
AB  - RATIONALE: The frequency of pneumonia and bronchiolitis exhibits considerable
      variation in otherwise healthy children, and suspected risk factors explain only
      a minor proportion of the variation. We hypothesized that alterations in the
      airway microbiome in early life may be associated with susceptibility to
      pneumonia and bronchiolitis in young children. OBJECTIVES: To investigate the
      relation between neonatal airway colonization and pneumonia and bronchiolitis
      during the first 3 years of life. METHODS: Participants comprised children of the
      Copenhagen Prospective Studies on Asthma in Childhood2000 (COPSAC2000) cohort, a
      prospective birth cohort study of 411 children born to mothers with asthma.
      Aspirates from the hypopharynx at age 4 weeks were cultured for Streptococcus
      pneumoniae, Haemophilus influenzae, Moraxella catarrhalis, and Staphylococcus
      aureus. Clinical information on pneumonia and bronchiolitis within the first 3
      years of life was prospectively collected by the research physicians at the
      center. Analyses were adjusted for covariates associated with pneumonia and
      bronchiolitis and bacterial airway colonization. MEASUREMENTS AND MAIN RESULTS:
      Hypopharyngeal aspirates and full clinical follow-up until 3 years of age were
      available for 265 children. Of these, 56 (21%) neonates were colonized with S.
      pneumoniae, H. influenzae, and/or M. catarrhalis at 4 weeks of age. Colonization
      with at least one of these microorganisms (but not S. aureus) was significantly
      associated with increased incidence of pneumonia and bronchiolitis (adjusted
      incidence rate ratio, 1.79 [1.29-2.48]; P < 0.005) independently of concurrent or
      later asthma. CONCLUSIONS: Neonatal airway colonization with S. pneumoniae, H.
      influenzae, or M. catarrhalis is associated with increased risk of pneumonia and
      bronchiolitis in early life independently of asthma. This suggests a role of
      pathogenic bacterial colonization of the airways in neonates for subsequent
      susceptibly to pneumonia and bronchiolitis.

PMID- 24090103
TI  - Mechanistic insights into mode of action of a potent natural antagonist of orexin
      receptor-1 by means of high throughput screening and molecular dynamics
      simulations.
AB  - Insomnia is one of the most common clinical problems being faced by people all
      over the world. It adversely affects the routine life of these patients giving
      rise to even other health issues like hypertension, diabetes, obesity,
      depression, heart attack, and stroke. Orexin receptor-1 (OX1R), a noteworthy drug
      target, when inhibited can promote sleepiness in people suffering from such
      conditions. OX1R is a G-protein coupled receptor which is conserved throughout
      the mammalian species and is located primarily in hypothalamus and locus
      coeruleus. The present study aims at identifying potent natural-origin inhibitors
      of OX1R capable of affecting the arousal and sleep pattern. In the present work,
      we have screened a large dataset of natural compounds against OX1R using high
      throughput screening and high precision docking approaches. Molecular dynamics
      simulations were carried out to study the dynamical behavior of the top scoring
      compound. We also provided mechanistic insights into the binding mode of action
      of this compound. The study provides evidence for consideration of this natural
      molecule as prospective lead in treatment of insomnia. 

PMID- 24090101
TI  - Phenotyping dividing cells in mouse models of neurodegenerative basal ganglia
      diseases.
AB  - BACKGROUND: Mice generated by a Cre/LoxP transgenic paradigm were used to model
      neurodegenerative basal ganglia disease of which Huntington disease (HD) is the
      prototypical example. In HD, death occurs in striatal projection neurons as well
      as cortical neurons. Cortical and striatal neurons that express the D1 dopamine
      receptor (Drd1a) degenerate in HD. The contribution that death of specific
      neuronal cell populations makes to the HD disease phenotype and the response of
      the brain to loss of defined cell subtypes is largely unknown. METHODS: Drd1a
      expressing cells were targeted for cell death and three independent lines
      generated; a striatal-restricted line, a cortical-restricted line and a global
      line in which Drd1a cells were deleted from both the striatum and cortex. Two
      independent experimental approaches were used. In the first, the proliferative
      marker Ki-67 was used to identify proliferating cells in eighty-week-old mice
      belonging to a generic global line, a global in which Drd1a cells express green
      fluorescent protein (GFP-global) and in eighty-week-old mice of a cortical line.
      In the second experiment, the proliferative response of four-week-old mice
      belonging to GFP-global and striatal lines was assessed using the thymidine
      analogue BrdU. The phenotype of proliferating cells was ascertained by double
      staining for BrdU and Olig2 (an oligodendrocyte marker), Iba1 (a microglial cell
      marker), S100beta (an astroglial cell marker), or NeuN (a neuronal cell marker).
      RESULTS: In the first study, we found that Ki-67-expressing cells were restricted
      to the striatal side of the lateral ventricles. Control mice had a greater number
      of Ki-67+ cells than mutant mice. There was no overlap between Ki-67 and GFP
      staining in control or mutant mice, suggesting that cells did not undergo cell
      division once they acquired a Drd1a phenotype. In contrast, in the second study
      we found that BrdU+ cells were identified throughout the cortex, striatum and
      periventricular region of control and mutant mice. Mutant mice from the GFP
      global line showed increased BrdU+ cells in the cortex, striatum and
      periventricular region relative to control. Striatal line mutant mice had an
      increased number of BrdU+ cells in the striatum and periventricular region, but
      not the cortex. The number of microglia, astrocytes, oligodendrocytes and neurons
      generated from dividing progenitors was increased relative to control mice in
      most brain regions in mutant mice from the GFP-global line. In contrast, striatal
      line mutant mice displayed an increase only in the number of dividing microglia
      in striatal and periventricular regions. CONCLUSIONS: Genetically programmed post
      natal ablation of Drd1a-expressing neurons is associated with an extensive
      proliferative response involving multiple cell lineages. The nature of the tissue
      response has the potential not only to remove cellular debris but also to forge
      physiologically meaningful brain repair. Age related deficits in proliferation
      are seen in mutant lines. A blunted endogenous reparative response may underlie
      the cumulative deficits characteristic of age related neurodegeneration.

PMID- 24090104
TI  - The orthoptic slit lamp.
AB  - Recently we presented our concept of "videography with the slit lamp," which
      provides an imaging solution for nearly every pathological finding in
      ophthalmology. This paper deals with the changes that must be made to prepare the
      slit lamp for documenting squint. To achieve this goal we propose: 1. Changes in
      the observation system: minus lenses in front of the objective of the slit lamp
      to achieve a sharp image of both eyes (eg, -8 diopters [dpt] if the patient sits
      at a distance of 50 cm). 2. Changes in the illumination system: minimizing the
      narrowed angle between illumination and observation axis by holding a
      "recentration" prism of 14 dpt horizontally in front of the slit light. This
      procedure creates equally sufficient illumination of the patient's face and
      central corneal reflexes. 3. Recording clinical findings with a digital recorder.
      This enables us to identify binocular eye positions, which sometimes last only
      part of a second, eg, in latent or intermittent strabism. 4. Visualizing clinical
      findings by using Microsoft PowerPoint(r) to build up 9-gaze composites or adjust
      corneal reflexes on subsequent foils. Changes in binocular eye positions (eg,
      after surgery, but also during diagnostic covering) can be made visible by
      flickering between the foils to compare.

PMID- 24090105
TI  - Isotope labeling-based quantitative proteomics of developing seeds of castor oil
      seed (Ricinus communis L.).
AB  - In this study, we used a mass spectrometry-based quantification approach
      employing isotopic (ICPL) and isobaric (iTRAQ) labeling to investigate the
      pattern of protein deposition during castor oil seed (Ricinus communis L.)
      development, including that of proteins involved in fatty acid metabolism, seed
      storage proteins (SSPs), toxins, and allergens. Additionally, we have used off
      line hydrophilic interaction chromatography (HILIC) as a step of peptide
      fractionation preceding the reverse-phase nanoLC coupled to a LTQ Orbitrap. We
      were able to identify a total of 1875 proteins, and from these 1748 could be
      mapped to extant castor gene models, considerably expanding the number of
      proteins so far identified from developing castor seeds. Cluster validation and
      statistical analysis resulted in 975 protein trend patterns and the relative
      abundance of 618 proteins. The results presented in this work give important
      insights into certain aspects of the biology of castor oil seed development such
      as carbon flow, anabolism, and catabolism of fatty acid and the pattern of
      deposition of SSPs, toxins, and allergens such as ricin and 2S albumins. We also
      found, for the first time, some genes of SSP that are differentially expressed
      during seed development. 

PMID- 24090106
TI  - Urodynamic patterns after traumatic spinal cord injury.
AB  - OBJECTIVES: To study the correlation between neurological level of spinal injury
      and bladder functions as detected by urodynamic study. STUDY DESIGN: Analytical
      study. SETTING AND PARTICIPANTS: Seventy individuals with traumatic spinal cord
      injury (SCI) admitted to the Department of Physical Medicine and Rehabilitation,
      S.M.S. Medical College and Hospital, Jaipur. Detailed clinical, neurological
      evaluation as per American Spinal Injury Association Classification and
      radiological assessment were done along with clinical examination of bladder and
      urodynamic study. RESULTS: Out of 65 patients with suprasacral injuries, 53
      (81.5%) demonstrated hyperreflexia with or without detrusor sphincter
      dyssynergia, 6 (9.2%) detrusor areflexia, and 6 (9.2%) had normal bladders, 41
      (59.4%) low compliance (<20 ml/cmH2O), and 47 (72.30%) had high detrusor leak
      pint pressures (>40 cmH2O). Of the five patients with sacral injuries, one (20%)
      showed detrusor hyperreflexia, four (80%) detrusor areflexia, and one (20%) had
      low bladder compliance; all five (100%) had high detrusor leak point pressures.
      CONCLUSIONS: The correlation between somatic neurologic findings, spinal imaging
      studies, and urodynamic findings in patients with SCI is not exact. Therefore,
      bladder management should not completely rely only on clinical bladder evaluation
      or neurological examination alone, but should always include urodynamic studies.

PMID- 24090107
TI  - Clinical evaluation of multi-atlas based segmentation of lymph node regions in
      head and neck and prostate cancer patients.
AB  - BACKGROUND: Semi-automated segmentation using deformable registration of selected
      atlas cases consisting of expert segmented patient images has been proposed to
      facilitate the delineation of lymph node regions for three-dimensional conformal
      and intensity-modulated radiotherapy planning of head and neck and prostate
      tumours. Our aim is to investigate if fusion of multiple atlases will lead to
      clinical workload reductions and more accurate segmentation proposals compared to
      the use of a single atlas segmentation, due to a more complete representation of
      the anatomical variations. METHODS: Atlases for lymph node regions were
      constructed using 11 head and neck patients and 15 prostate patients based on
      published recommendations for segmentations. A commercial registration software
      (Velocity AI) was used to create individual segmentations through deformable
      registration. Ten head and neck patients, and ten prostate patients, all
      different from the atlas patients, were randomly chosen for the study from
      retrospective data. Each patient was first delineated three times, (a) manually
      by a radiation oncologist, (b) automatically using a single atlas segmentation
      proposal from a chosen atlas and (c) automatically by fusing the atlas proposals
      from all cases in the database using the probabilistic weighting fusion
      algorithm. In a subsequent step a radiation oncologist corrected the segmentation
      proposals achieved from step (b) and (c) without using the result from method (a)
      as reference. The time spent for editing the segmentations was recorded
      separately for each method and for each individual structure. Finally, the Dice
      Similarity Coefficient and the volume of the structures were used to evaluate the
      similarity between the structures delineated with the different methods. RESULTS:
      For the single atlas method, the time reduction compared to manual segmentation
      was 29% and 23% for head and neck and pelvis lymph nodes, respectively, while
      editing the fused atlas proposal resulted in time reductions of 49% and 34%. The
      average volume of the fused atlas proposals was only 74% of the manual
      segmentation for the head and neck cases and 82% for the prostate cases due to a
      blurring effect from the fusion process. After editing of the proposals the
      resulting volume differences were no longer statistically significant, although a
      slight influence by the proposals could be noticed since the average edited
      volume was still slightly smaller than the manual segmentation, 9% and 5%,
      respectively. CONCLUSIONS: Segmentation based on fusion of multiple atlases
      reduces the time needed for delineation of lymph node regions compared to the use
      of a single atlas segmentation. Even though the time saving is large, the quality
      of the segmentation is maintained compared to manual segmentation.

PMID- 24090108
TI  - Fabrication of c-axis oriented ZSM-5 hollow fibers based on an in situ solid
      solid transformation mechanism.
AB  - We report, for the first time, the preparation of novel c-axis oriented ZSM-5
      hollow fibers by a combination of seeding and steam-assisted crystallization
      method using quartz fibers as the temporary soft substrate and Si source. The
      growth of such unique structure undergoes the development of a b-axis oriented
      ZSM-5 cylinder, followed by the growth of c-axis oriented ZSM-5 crystals
      vertically inside the cylinder and then outside the cylinder, by an in situ solid
      solid transformation mechanism. The obtained ZSM-5 hollow fibers are composed of
      pure hierarchical ZSM-5 crystals with high crystallinity, good structural
      stability, and high surface area and have potential applications for
      microreactors, separators, and catalysts. The catalytic performance of ZSM-5
      hollow fibers is tested in the methanol to gasoline reaction, as an example of
      their practical application. They exhibit both higher yield of gasoline and far
      longer lifetime compared to the conventional ZSM-5 due to the improved mass and
      heat diffusion rate inside the meso-/macropores of c-axis oriented structure. 

PMID- 24090109
TI  - Aromatase inhibitor treatment with an intravaginal device and its effect on pre
      ovulatory ovarian follicles in a bovine model.
AB  - BACKGROUND: Letrozole, a non-steroidal aromatase inhibitor, prevents the body
      from producing its own estrogen. The objectives of the present study were to test
      the hypotheses that letrozole treatment, initiated prior to selection of the
      preovulatory dominant follicle, will induce the growth of more than one follicle
      to a pre-ovulatory size, and will delay ovulation. METHODS: Post-pubertal beef
      heifers were given two luteolytic doses of PGF (12 h apart) and monitored by
      ultrasonography for ovulation. Five to eight days later, ovarian follicular wave
      emergence was synchronized by ultrasound-guided transvaginal follicular ablation
      (Day 0=wave emergence) and a luteolytic dose of PGF was given 60 and 72 h later.
      On Day 1, heifers were divided randomly into two groups (n=15/group) and an
      intravaginal device containing 1 g of letrozole or a blank device (control) was
      inserted. The intravaginal devices were removed on Day 7, or at the time of
      ovulation, whichever occurred first. Transrectal ultrasonography and blood sample
      collection were performed daily from the day of ablation to 12 days after
      subsequent ovulation. RESULTS: The mean (+/-SEM) interval from device placement
      to ovulation was longer in letrozole-treated animals compared to controls (6.1+/
      0.25 vs 5.1+/-0.26 days, respectively; P<0.01). Single dominant follicles were
      present in both groups. The day-to-day diameter profiles of the dominant
      follicles of the ovulatory wave were larger (P<0.05) and the maximum diameters
      greater in letrozole-treated heifers (14.6+/-0.51 vs 12.4+/-0.53 mm,
      respectively; P<0.01). The diameter profile of the corpus luteum (CL) that formed
      after treatment did not differ between groups; however, plasma progesterone
      concentrations were higher (P<0.01) in heifers treated with letrozole. Estradiol
      concentrations were reduced following letrozole treatment (P<0.05), although a
      preovulatory rise of estradiol occurred in both groups. CONCLUSIONS:
      Administration of letrozole with an intravaginal device during growth of the
      ovulatory follicle delayed ovulation by 24 h and resulted in the formation of a
      CL that secreted higher levels of progesterone. A sustained-release intravaginal
      device may be useful for the development of an aromatase inhibitor-based protocol
      to control ovulation for herd synchronization and to enhance fertility by
      increasing circulating progesterone concentrations during the first 7 days post
      ovulation in cattle.

PMID- 24090110
TI  - Ligand binding determinants for angiotensin II type 1 receptor from computer
      simulations.
AB  - The ligand binding determinants for the angiotensin II type 1 receptor (AT1R), a
      G protein-coupled receptor (GPCR), have been characterized by means of computer
      simulations. As a first step, a pharmacophore model of various known AT1R ligands
      exhibiting a wide range of binding affinities was generated. Second, a structural
      model of AT1R was built making use of the growing set of crystal structures of
      GPCRs, which was further used for the docking of the AT1R ligands based on the
      devised pharmacophore model. Next, ligand-receptor-lipid bilayer systems were
      studied by means of molecular dynamics (MD) simulations. Overall, the present
      study has permitted, combining the pharmacophore model with binding free energy
      calculations obtained from the MD simulations, to propose the molecular
      mechanisms by which sartans interact with AT1R. 

PMID- 24090111
TI  - Trends in dental visiting avoidance due to cost in Australia, 1994 to 2010: an
      age-period-cohort analysis.
AB  - BACKGROUND: The cost of dental care may be a barrier to regular dental attendance
      with the proportion of the Australian population avoiding or delaying care due to
      cost increasing since 1994. This paper explores the extent to which age, period
      and cohort factors have contributed to the variation in avoiding or delaying
      visiting a dentist because of cost. METHODS: Data were obtained from four
      national dental telephone interview surveys of Australian residents aged five
      years and over conducted in 1994, 1999, 2004 and 2010 (response rates 48%-72%).
      The trend in the percentage of persons avoiding or delaying visiting a dentist
      because of cost was analysed by means of a standard cohort table and more formal
      age-period-cohort analyses using a nested models framework. RESULTS: There was an
      overall increase in the proportion of people avoiding or delaying visiting a
      dentist indicating the presence of period effects. Financial barriers were also
      associated with age such that the likelihood of avoiding because of cost was
      highest for those in their mid-late twenties and lowest in both children and
      older adults. Cohort effects were also present although the pattern of effects
      differed between cohorts. CONCLUSION: The findings of this study suggest that, in
      addition to the increase in costs associated with dental care, policies targeting
      specific age groups and income levels may be contributing to the inequality in
      access to dental care.

PMID- 24090112
TI  - Photocatalytic bacterial inactivation by TiO2-coated surfaces.
AB  - The aim of this study was the evaluation of the photoactivated antibacterial
      activity of titanium dioxide (TiO2)-coated surfaces. Bacterial inactivation was
      evaluated using TiO2-coated Petri dishes. The experimental conditions optimized
      with Petri dishes were used to test the antibacterial effect of TiO2-coated
      ceramic tiles. The best antibacterial effect with Petri dishes was observed at
      180, 60, 30 and 20 min of exposure for Escherichia coli, Staphylococcus aureus,
      Pseudomonas putida and Listeria innocua, respectively. The ceramic tiles
      demonstrated a photoactivated bactericidal effect at the same exposure time. In
      general, no differences were observed between the antibacterial effect obtained
      with Petri dishes and tiles. However, the photochemical activity of Petri dishes
      was greater than the activity of the tiles.Results obtained indicates that the
      TiO2-coated surfaces showed a photoactivated bactericidal effect with all
      bacteria tested highlighting that the titania could be used in the ceramic and
      building industry for the production of coated surfaces to be placed in
      microbiologically sensitive environments, such as the hospital and food industry.

PMID- 24090113
TI  - Contralateral referred pain in a patient with intramedullary spinal cord
      metastasis from extraskeletal small cell osteosarcoma.
AB  - CONTEXT: Referred pain has been observed in some patients after cordotomy,
      wherein noxious stimulus applied to a region rendered analgesic by cordotomy
      produces pain at a spot different from the one where the noxious stimulus is
      applied. We report a patient who had intramedullary spinal cord metastasis of
      extraskeletal small cell osteosarcoma, a rare form of metastatic disease, and
      experienced contralateral referred pain. FINDINGS: Initially, the patient had a
      mass in the left posterior neck region and later developed a large extradural
      mass at the C3-C7 level. The masses were excised, and the histological findings
      led to a diagnosis of small cell osteosarcoma. He underwent chemotherapy and
      radiation therapy. He experienced numbness in his left leg; subsequently, the
      numbness slowly spread up the thigh to the left side of the abdomen. When pinched
      in the numb area on the left side of the body, he felt as though he had been
      pinched in both that area and the corresponding area on the right side. A
      magnetic resonance imaging scan showed an enhancing lesion in the right side of
      the cord at the C6-C7 level. CONCLUSION/CLINICAL RELEVANCE: An intramedullary
      spinal cord metastasis can arise from primary extraskeletal small cell
      osteosarcoma and cause contralateral referred pain, especially in a mirror-image
      location. Contralateral referred pain may be caused by a subsidiary pathway
      comprising ascending chains of short neurons that link the dorsal horn neurons
      longitudinally and latitudinally.

PMID- 24090115
TI  - Control of self-assembled morphology and molecular packing of asymmetric
      glycolipids by association/dissociation with poly(thiopheneboronic acid).
AB  - The molecular packing and self-assembled morphologies of asymmetric
      bolaamphiphiles, N-(2-aminoethyl)-N'-(beta-d-glucopyranosyl)alkanediamide [1(n),
      n = 12, 14, 16, 17, 18, and 20], were precisely controlled by
      association/dissociation with poly(thiopheneboronic acid) (PTB). Differential
      scanning calorimetry, X-ray diffraction, and infrared spectroscopy revealed that
      the starting film of 1(n) associated with 1 equiv of the boronic acid moiety of
      PTB, (Film-1(n)PTB), had antiparallel molecular packing of 1(n) moiety within the
      monolayer membranes. However, the molecular packing of the starting film that
      contained 0.5 equiv of the boronic acid moiety of PTB (Film-2eq1(n)PTB) was
      parallel. The dispersion of Film-1(n)PTB in water gave only nanotapes, whereas
      that of Film-2eq1(n)PTB in water selectively formed nanotubes, through a
      dissociation reaction of PTB based on the hydrolysis of the boronate esters in
      the complexes. The nanotapes and nanotubes memorized the antiparallel and
      parallel molecular packing of the starting films, respectively. Changes in the
      length of the oligomethylene spacer of 1(n) never affected the molecular packing
      or self-assembled morphologies. However, the inner diameters of the nanotubes
      increased irregularly in the range of 67.9-79.6 nm as the length of the
      oligomethylene spacer of 1(n) increased from n = 12 to n = 18. 

PMID- 24090114
TI  - Development of maternal and foetal immune responses in cattle following
      experimental challenge with Neospora caninum at day 210 of gestation.
AB  - This study examined the immunological responses of pregnant cattle and their
      foetuses following an experimental challenge with live Neospora caninum
      tachyzoites at day 210 of gestation. Animals were bled prior to and weekly
      throughout the experiment and sacrificed at 14, 28, 42 and 56 days post
      inoculation (dpi). At post mortem examination, samples of lymph nodes and spleen
      were collected from both dam and foetus for immunological analysis. Subcutaneous
      (sc) inoculation over the left prefemoral (LPF) lymph node of pregnant cattle at
      day 210 of gestation, led to the vertical transmission of parasites by 14 dpi,
      however no foetal deaths were observed in the infected animals. Foetuses from
      infected dams mounted Neospora-specific humoral and cell-mediated immune (CMI)
      responses by 14 dpi. These responses involved anti-Neospora IgG, antigen-specific
      lymphocyte proliferation, and the production of the cytokines IFN-gamma,
      interleukin (IL)-4 and IL-10. There was also evidence of innate immunity during
      the response against Neospora from infected dams, with statistically significant
      (p < 0.05) increases in mean expression of toll like receptors (TLR)-2 on 56 dpi
      in maternal spleen, LPF, right prefemoral (RPF), left uterine (LUL) and right
      uterine (RUL) lymph nodes and TLR-9 in retropharyngeal (RLN), LPF and RPF lymph
      nodes from 28 dpi. Statistically significant (p < 0.05) increases in mean TLR-9
      were detected in spleen samples from foetuses of infected dams, compared to the
      foetuses from control animals. Our results show that vertical transmission of the
      parasite occurred in all infected dams, with their foetuses showing effective
      Neospora-specific cell mediated, humoral and innate immune responses.

PMID- 24090116
TI  - Risk factors for wound disruption following cesarean delivery.
AB  - OBJECTIVE: Risk factors for post-cesarean wound infection, but not disruption,
      are well-described in the literature. The primary objective of this study was to
      identify risk factors for non-infectious post-cesarean wound disruption. METHODS:
      Secondary analysis was conducted using data from a single-center randomized
      controlled trial of staple versus suture skin closure in women >=24 weeks'
      gestation undergoing cesarean delivery. Wound disruption was defined as
      subcutaneous skin or fascial dehiscence excluding primary wound infections.
      Composite wound morbidity (disruption or infection) was examined as a secondary
      outcome. Patient demographics, medical co-morbidities, and intrapartum
      characteristics were evaluated as potential risk factors using multivariable
      logistic regression. RESULTS: Of the 398 randomized patients, 340, including 26
      with disruptions (7.6%) met inclusion criteria and were analyzed. After
      multivariable adjustments, African-American race (aOR 3.9, 95% CI 1.1-13.8) and
      staple - as opposed to suture - wound closure (aOR 5.4, 95% CI 1.8-16.1) remained
      significant risk factors for disruption; non-significant increases were observed
      for body mass index >=30 (aOR 2.1, 95% CI 0.6-7.5), but not for diabetes mellitus
      (aOR 0.9, 95% CI 0.3-2.9). RESULTS for composite wound morbidity were similar.
      CONCLUSIONS: Skin closure with staples, African-American race, and considering
      the relatively small sample size, potentially obesity are associated with
      increased risk of non-infectious post-cesarean wound disruption.

PMID- 24090117
TI  - Exploiting dendritic cells in the development of cancer vaccines.
AB  - Due to their central role in priming and modulating the immune response,
      dendritic cells (DCs) represent an ideal instrument for the design of effective
      immunotherapeutic strategies for cancer patients. Recent advancement on the
      knowledge of the numerous DC subtypes, their functions and T-cell polarizing
      abilities has led to the development of several protocols for the ex vivo
      differentiation of autologous DCs and their loading with tumor-associated
      antigens. Moreover, novel strategies for the in vivo targeting of tumor antigens
      and adjuvants to natural DC subsets have been developed. Despite the large number
      of clinical studies carried out in cancer patients, a consensus on the optimal
      treatment modalities has not been reached yet. In this review, we summarize our
      current knowledge on DC biology and on DC use in clinical trials. Special
      attention is given to the many open issues regarding DC-based vaccination to
      sensitize researchers in the field to the compelling need of conducting
      comparative studies systematically addressing the still unresolved problems. 

PMID- 24090118
TI  - Thunderclap headache as a presentation of spontaneous spinal epidural hematoma
      with spontaneous recovery.
AB  - BACKGROUND: Spontaneous spinal epidural hematoma (SSEH) is a rare spinal cord
      compression disorder. Thunderclap headache mimicking subarachnoid hemorrhage as
      an initial manifestation of this disorder has been scarcely reported. Moreover,
      the neurological outcome of conservative treatment is satisfactory only in some
      clinical settings. The unusual presentation and mechanisms for spontaneous
      recovery of SSEH are discussed. OBJECTIVE: To report a case of SSEH that
      presented with acute severe headache that mimicked subarachnoid hemorrhage. After
      a period of neurological deficit, spontaneous improvement was seen, which
      progressed to full recovery without neurosurgical intervention. FINDINGS: A 62
      year-old man presented with acute occipital headache and neck stiffness for which
      subarachnoid hemorrhage was initially suspected. An emergency computed
      tomographic brain scan and cerebrospinal fluid analysis excluded subarachnoid
      hemorrhage. Later, he developed acute paraparesis, hypoesthesia up to the fourth
      thoracic dermatomal level (T4) as well as bowel and bladder dysfunction. The
      magnetic resonance imaging eventually revealed spinal epidural hematoma, located
      anterior to C7 through T4 spinal level. He had no previous history of spinal
      injury, systemic, and hematological disorders. The neurological recovery began 20
      hours after the onset and continued until complete recovery, 4 months after the
      onset without neurosurgical intervention. CONCLUSION: SSEH could sometimes
      imitate subarachnoid hemorrhages when it located in the cervical region.
      Spontaneous recovery of SSEH without surgical intervention might be possible in
      cases with continuing neurological recovery, although the recovery began much
      later in the clinical course.

PMID- 24090119
TI  - Three new polyketides from marine-derived fungus Penicillium citrinum SCSGAF
      0167.
AB  - Three new polyketides penicitrinol G (1), penicitrinol H (2) and 2,11-dihydroxy-1
      methoxycarbonyl-9-carboxylxanthone (3) together with one known cathepsin B
      inhibitor chrysophanol (4) were isolated from a culture broth of marine-derived
      fungus Penicillium citrinum SCSGAF 0167. Their structures were determined by
      spectroscopic methods. Compound 4 exhibited inhibitory activity against cathepsin
      B with IC50 value of 1.7 MUM. 

PMID- 24090120
TI  - Efficient, stereodivergent access to 3-piperidinols by traceless P(OEt)3
      cyclodehydration.
AB  - A stereodivergent and highly diastereoselective (dr up to >19:1 for both
      isomers), step economic (5-6 steps), and scalable synthesis (up to 14 g) of cis-
      and trans-2-substituted 3-piperidinols, the core motif of numerous bioactive
      compounds, providing efficient access to the NK-1 inhibitor L-733,060 is
      presented. Additionally, a "traceless" (referring to the simplified byproduct
      separation) cyclodehydration realizing simple P(OEt)3 as a substitute for PPh3 is
      developed. 

PMID- 24090121
TI  - Halonium ion triggered rearrangement of unsaturated benzo-annulated bi- and
      tricyclic sulfonamides.
AB  - The halonium ion mediated 1,2-Wagner-Meerwein-type rearrangement of a series of
      benzo-fused bi- and tricyclic sulfonamides is reported. During this rearrangement
      the carbon-carbon bond that migrates was selectively set in the intramolecular
      Mizoroki-Heck (IHR) synthesis of the starting materials. Consequently, this
      method constitutes a means to access the regioisomeric series of cyclic
      sulfonamides not observed during the Mizoroki-Heck reaction. 

PMID- 24090122
TI  - Exploring the publications in three major orthodontic journals: a comparative
      analysis of two 5-year periods.
AB  - OBJECTIVE: To analyze the types of articles and authorship characteristics of
      three orthodontic journals--American Journal of Orthodontics and Dentofacial
      Orthopedics (AJODO), The Angle Orthodontist (AO), and European Journal of
      Orthodontics (EJO)--published between 2008 and 2012 and to assess the differences
      in content within this period and an earlier period of 1998 to 2002. MATERIALS
      AND METHODS: Each journal's content was accessed through the web edition. From
      each article, the following parameters were recorded: article type, number of
      authors, number of affiliations, source of article (referring to the first
      author's affiliation), and geographic origin. Descriptive statistics were
      performed and selected parameters were analyzed with the Pearson chi-square or
      Fisher exact test for independence at the .05 level of significance. RESULTS:
      Review of differences between the two periods showed that the number of
      publications was almost double. The percentages of multi-authored articles
      increased. Fewer studies derived from the United States/Canada and European Union
      countries. Increases for articles from non-European Union countries, Asia, and
      other countries were found. Characteristics of the second period showed that the
      EJO and AO published more research articles, whereas the AJODO regularly
      published case reports and other articles. Approximately 75% of all studies
      derived from orthodontic departments. CONCLUSIONS: The publications from 1998
      2002 and 2008-2012 were significantly different both in terms of numbers and
      characteristics. Within 2008-2012 there were notable differences between the
      three journals concerning the type and origin of the publications.

PMID- 24090123
TI  - Evaluation of facial attractiveness for patients with malocclusion: a machine
      learning technique employing Procrustes.
AB  - OBJECTIVE: To establish an objective method for evaluating facial attractiveness
      from a set of orthodontic photographs. MATERIALS AND METHODS: One hundred eight
      malocclusion patients randomly selected from six universities in China were
      randomly divided into nine groups, with each group containing an equal number of
      patients with Class I, II, and III malocclusions. Sixty-nine expert Chinese
      orthodontists ranked photographs of the patients (frontal, lateral, and frontal
      smiling photos) before and after orthodontic treatment from "most attractive" to
      "least attractive" in each group. A weighted mean ranking was then calculated for
      each patient, based on which a three-point scale was created. Procrustes
      superimposition was conducted on 101 landmarks identified on the photographs. A
      support vector regression (SVR) function was set up according to the coordinate
      values of identified landmarks of each photographic set and its corresponding
      grading. Its predictive ability was tested for each group in turn. RESULTS: The
      average coincidence rate obtained for comparisons of the subjective ratings with
      the SVR evaluation was 71.8% according to 18 verification tests. CONCLUSIONS:
      Geometric morphometrics combined with SVR may be a prospective method for
      objective comprehensive evaluation of facial attractiveness in the near future.

PMID- 24090124
TI  - Randomized trial of infusion set function: steel versus teflon.
AB  - BACKGROUND: This study compared infusion set function for up to 1 week using
      either a Teflon((r)) (Dupont(TM), Wilmington, DE) catheter or a steel catheter
      for insulin pump therapy in type 1 diabetes mellitus. SUBJECTS AND METHODS:
      Twenty subjects participating in a randomized, open-labeled, crossover study were
      asked to wear two Quick-Set((r)) and two Sure-T((r)) infusion sets (both from
      Medtronic Minimed, Northridge, CA) until the infusion set failed or was worn for
      1 week. All subjects wore a MiniMed continuous glucose monitoring system for the
      duration of the study. RESULTS: One subject withdrew from the study. There were
      38 weeks of Sure-T wear and 39 weeks of Quick-Set wear with no difference in the
      survival curves of the infusion sets. There was, however, a 15% initial failure
      rate with the Teflon infusion set. After 7 days, both types of infusion sets had
      a 64% failure rate. Overall, 30% failed because of hyperglycemia and a failed
      correction dose, 13% were removed for pain, 10% were pulled out by accident, 10%
      had erythema and/or induration of>10 mm, 5% fell out because of loss of adhesion,
      and 4% were removed for infection. The main predictor of length of wear was the
      individual subject. There was no increase in hyperglycemia or daily insulin
      requirements when an infusion set was successfully used for 7 days (n=25 of 77
      weeks). CONCLUSIONS: We found no difference between steel and Teflon infusion
      sets in their function over 7 days, although 15% of Teflon sets failed because of
      kinking on insertion. The strongest predictor of prolonged 7-day infusion set
      function was the individual subject, not the type of infusion set.

PMID- 24090128
TI  - Origin and scope of long-range stabilizing interactions and associated SOMO-HOMO
      conversion in distonic radical anions.
AB  - High-level quantum-chemical methods have been used to study the scope and
      physical origin of the significant long-range stabilizing interactions between
      nonmutually conjugated anion and radical moieties in SOMO-HOMO converted distonic
      radical anions. In such species, deprotonation of the acid fragment can stabilize
      the remote radical by tens of kilojoules, or, analogously, formation of a stable
      radical (by abstraction or homolytic cleavage reactions) increases the acidity of
      a remote acid by several pKa units. This stabilization can be broadly classified
      as a new type of polar effect that originates in Coloumbic interactions but, in
      contrast to standard polar effects, persists in radicals with no charge-separated
      (i.e., dipole) resonance contributors, is nondirectional, and hence of extremely
      broad scope. The stabilization upon deprotonation is largest when a highly
      delocalized radical is combined with an initially less stable anion (i.e., the
      conjugate base of a weaker acid), and is negligible for highly localized radicals
      and/or stable anions. The effect is largest in the gas phase and low-polarity
      solvents but is quenched in water, where the anion is sufficiently stabilized.
      These simple rules can be employed to design various switchable compounds able to
      reversibly release radicals in response to pH for use in, for example, organic
      synthesis or nitroxide-mediated polymerization. Moreover, given its wide chemical
      scope, this effect is likely to influence the protonation state of many
      biological substrates under radical attack and may contribute to enzyme
      catalysis. 

PMID- 24090125
TI  - A study to evaluate the acceptability, feasibility and impact of packaged
      interventions ("Diarrhea Pack") for prevention and treatment of childhood
      diarrhea in rural Pakistan.
AB  - BACKGROUND: Diarrhea remains one of the leading public health issues in
      developing countries and is a major contributor in morbidity and mortality in
      children under five years of age. Interventions such as ORS, Zinc, water
      purification and improved hygiene and sanitation can significantly reduce the
      diarrhea burden but their coverage remains low and has not been tested as
      packaged intervention before. This study attempts to evaluate the package of
      evidence based interventions in a "Diarrhea Pack" through first level health care
      providers at domiciliary level in community based settings. This study sought to
      evaluate the acceptability, feasibility and impact of diarrhea Pack on diarrhea
      burden. METHODS: A cluster randomized design was used to evaluate the objectives
      of the project a union council was considered as a cluster for analysis, a total
      of eight clusters, four in intervention and four in control were included in the
      study. We conducted a baseline survey in all clusters followed by the delivery of
      diarrhea Pack in intervention clusters through community health workers at
      domiciliary level and through sales promoters to health care providers and
      pharmacies. Four quarterly surveillance rounds were conducted to evaluate the
      impact of diarrhea pack in all clusters by an independent team of Field workers.
      RESULTS: Both the intervention and control clusters were similar at the baseline
      but as the study progress we found a significant increase in uptake of ORS and
      Zinc along with the reduction in antibiotic use, diarrhea burden and
      hospitalization in intervention clusters when compared with the control clusters.
      We found that the Diarrhea Pack was well accepted with all of its components in
      the community. CONCLUSION: The intervention was well accepted and had a
      productive impact on the uptake of ORS and zinc and reduction in the use of
      antibiotics. It is feasible to deliver interventions such as diarrhea pack
      through community health workers in community settings. The intervention has the
      potential to be scaled up at national level.

PMID- 24090129
TI  - Asymmetry in patient-related information disrupts pre-anesthetic patient
      briefing.
AB  - BACKGROUND: If one party has more or better information than the other, an
      information asymmetry can be assumed. The aim of the study was to identify the
      origin of incomplete patient-related preoperative information, which led to
      disruptions and losses of time during pre-anaesthetic patient briefing. We
      hypothesized that lower employees' educational level increases the amount of
      disruptive factors. METHODS: A prospective observational study design was used.
      Patient selection was depending on the current patient flow in the area of the
      clinic for pre-anesthetic patient briefing. Data were collected over a period of
      8 weeks. A stopwatch was used to record the time of disruptive factors. Various
      causes of time losses were grouped to facilitate statistical evaluation, which
      was performed by using the U-test of Mann and Whitney, Chi-square test or the
      Welch-t-test, as required. RESULTS: Out of 221 patients, 130 patient briefings
      (58.8%) had been disrupted. Residents were affected more often than consultants
      (66% vs. 47%, p = 0.008). Duration of disruptions was independent of the level of
      training and lasted about 2,5 minutes and 10% of the total time of patient
      briefing. Most time-consuming disruptive factors were missing study results,
      incomplete case histories, and limited patient compliance. CONCLUSIONS:
      Disruptions during pre-anesthetic patient briefings that were caused by patient
      related information asymmetry are common and account for a significant loss of
      time. The resultant costs justify investments in appropriate personnel
      allocation.

PMID- 24090130
TI  - Zinc-porphyrin based dyes for dye-sensitized solar cells.
AB  - We have designed seven efficient sensitizers based on the zinc-porphyrin
      structure for dye sensitized solar cells (DSSCs). The geometries, electronic
      properties, light harvesting efficiency (LHE), and electronic absorption spectra
      of these sensitizers are studied using density functional theory (DFT) and time
      dependent density functional theory (TD-DFT) calculations. We found that the
      designed sensitizers have smaller HOMO-LUMO energy with broadened and red-shifted
      absorption bands (300-1100 nm) having high molar extinction coefficient compared
      to the so far known best sensitizer (YD2-o-C8). The position of HOMO-LUMO energy
      level of these sensitizers ensures a positive effect on the process of electron
      injection and dye regeneration. Our theoretical calculations reveal that the new
      sensitizer can be used as a potential sensitizer for DSSCs compared to YD2-o-C8. 

PMID- 24090132
TI  - Investigation of the relationship between the metabolic profile of tobacco leaves
      in different planting regions and climate factors using a pseudotargeted method
      based on gas chromatography/mass spectrometry.
AB  - An improved pseudotargeted method using gas chromatography/mass spectrometry
      (GC/MS) was developed to investigate the metabolic profile of tobacco leaves from
      three planting regions (Yunnan, Guizhou, and Henan provinces). The analytical
      characteristics of the method with regard to reproducibility, precision,
      linearity, and stability were satisfactory for metabolic profiling study. Partial
      least-squares-discriminant analysis and hierarchical cluster analysis
      demonstrated that the metabolic profiles of tobacco from the Yunnan and Guizhou
      regions were different from that from the Henan province. The amino acid (e.g.,
      phenylalanine, leucine, and tyrosine) and carbohydrate (e.g., fructose,
      trehalose, and sucrose) contents were the highest in Henan tobacco. The highest
      contents of organic acids (e.g., isocitrate, citrate, and fumarate) of the TCA
      cycle and antioxidants (e.g., quinate, chlorogenic acid, and ascorbate) were
      found in Guizhou tobacco. The correlation coefficients between metabolite content
      and climate factors (rainfall, sunshine, and temperature) demonstrated that
      drought facilitated the accumulation of sugars and amino acids. The content of
      TCA cycle intermediates could be influenced by multiple climate factors. This
      study demonstrates that the pseudotargeted method with GC/MS is suitable for the
      investigation of the metabolic profiling of tobacco leaves and the assessment of
      differential metabolite levels related to the growing regions. 

PMID- 24090134
TI  - Antibody library display on a mammalian virus vector: combining the advantages of
      both phage and yeast display into one technology.
AB  - Utilizing a vaccinia virus based library technology, we previously developed an
      antibody discovery platform that enabled efficient selection of fully functional
      IgG antibodies from highly diverse immunoglobulin gene libraries expressed on the
      surface of mammalian cells. Recently, we have further modified this platform to
      enable efficient expression of a library of fully human antibodies on the surface
      of vaccinia virus; an enveloped mammalian virus. Similar in concept to phage
      display, conditions are utilized under which each vaccinia virion expresses a
      single antibody specificity on its surface. Various panning and magnetic bead
      based methods have been developed to allow screening of a library of vaccinia-
      MAb virions and selection of recombinant vaccinia virus encoding specific
      antibodies. Upon infection of mammalian cells the antibody is not only
      incorporated into newly produced virus, it is also displayed on the surface of
      the host cell. Similar to methods utilized in yeast display, the cells displaying
      vaccinia encoded antibody can also be selected using a combination of magnetic
      beads and cell sorting, and the virus encoding the specific antibody heavy and
      light chains readily recovered and analyzed. This technology allows for rapid
      high throughput selection of vaccinia-MAb virions in a cell free panning system,
      followed by cell based screening for high specificity and fine selection of
      optimal antibodies. 

PMID- 24090133
TI  - Tumour cells down-regulate CCN2 gene expression in co-cultured fibroblasts in a
      Smad7- and ERK-dependent manner.
AB  - BACKGROUND: Recent studies have revealed that interactions between tumour cells
      and the surrounding stroma play an important role in facilitating tumour growth
      and invasion. Stromal fibroblasts produce most of the extracellular matrix
      components found in the stroma. The aim of this study was to investigate
      mechanisms involved in tumour cell-mediated regulation of extracellular matrix
      and adhesion molecules in co-cultured fibroblasts. To this end, microarray
      analysis was performed on CCD-1068SK human fibroblast cells after direct co
      culture with MDA-MB-231 human breast tumour cells. RESULTS: We found that the
      expression of both connective tissue growth factor (CTGF/CCN2) and type I
      collagen was negatively regulated in CCD-1068SK fibroblast cells under direct co
      culture conditions. Further analysis revealed that Smad7, a known negative
      regulator of the Smad signalling pathway involved in CCN2 promoter regulation,
      was increased in directly co-cultured fibroblasts. Inhibition of Smad7 expression
      in CCD-1068SK fibroblasts resulted in increased CCN2 expression, while Smad7
      overexpression had the opposite effect. Silencing CCN2 gene expression in
      fibroblasts led, in turn, to a decrease in type I collagen mRNA and protein
      levels. ERK signalling was also shown to be impaired in CCD-1068SK fibroblasts
      after direct co-culture with MDA-MB-231 tumour cells, with Smad7 overexpression
      in fibroblasts leading to a similar decrease in ERK activity. These effects were
      not, however, seen in fibroblasts that were indirectly co-cultured with tumour
      cells. CONCLUSION: We therefore conclude that breast cancer cells require close
      contact with fibroblasts in order to upregulate Smad7 which, in turn, leads to
      decreased ERK signalling resulting in diminished expression of the stromal
      proteins CCN2 and type I collagen.

PMID- 24090131
TI  - High novelty-seeking rats are resilient to negative physiological effects of the
      early life stress.
AB  - Exposure to early life stress dramatically impacts adult behavior, physiology,
      and neuroendocrine function. Using rats bred for novelty-seeking differences and
      known to display divergent anxiety, depression, and stress vulnerability, we
      examined the interaction between early life adversity and genetic predisposition
      for high- versus low-emotional reactivity. Thus, bred Low Novelty Responder (bLR)
      rats, which naturally exhibit high anxiety- and depression-like behavior, and
      bred High Novelty Responder (bHR) rats, which show low anxiety/depression
      together with elevated aggression, impulsivity, and addictive behavior, were
      subjected to daily 3 h maternal separation (MS) stress postnatal days 1-14. We
      hypothesized that MS stress would differentially impact adult bHR/bLR behavior,
      physiology (stress-induced defecation), and neuroendocrine reactivity. While MS
      stress did not impact bHR and bLR anxiety-like behavior in the open field test
      and elevated plus maze, it exacerbated bLRs' already high physiological response
      to stress - stress-induced defecation. In both tests, MS bLR adult offspring
      showed exaggerated stress-induced defecation compared to bLR controls while bHR
      offspring were unaffected. MS also selectively impacted bLRs' (but not bHRs')
      neuroendocrine stress reactivity, producing an exaggerated corticosterone acute
      stress response in MS bLR versus control bLR rats. These findings highlight how
      genetic predisposition shapes individuals' response to early life stress. Future
      work will explore neural mechanisms underlying the distinct behavioral and
      neuroendocrine consequences of MS in bHR/bLR animals.

PMID- 24090135
TI  - Design of substituted imidazolidinylpiperidinylbenzoic acids as chemokine
      receptor 5 antagonists: potent inhibitors of R5 HIV-1 replication.
AB  - The redesign of the previously reported thiophene-3-yl-methyl urea series, as a
      result of potential cardiotoxicity, was successfully accomplished, resulting in
      the identification of a novel potent series of CCR5 antagonists containing the
      imidazolidinylpiperidinyl scaffold. The main redesign criteria were to reduce the
      number of rotatable bonds and to maintain an acceptable lipophilicity to mitigate
      hERG inhibition. The structure-activity relationship (SAR) that was developed was
      used to identify compounds with the best pharmacological profile to inhibit HIV
      1. As a result, five advanced compounds, 6d, 6e, 6i, 6h, and 6k, were further
      evaluated for receptor selectivity, antiviral activity against CCR5 using (R5)
      HIV-1 clinical isolates, and in vitro and in vivo safety. On the basis of these
      results, 6d and 6h were selected for further development.

PMID- 24090137
TI  - High-pressure synthesis of 5d cubic perovskite BaOsO3 at 17 GPa: ferromagnetic
      evolution over 3d to 5d series.
AB  - In continuation of the series of perovskite oxides that includes 3d(4) cubic
      BaFeO3 and 4d(4) cubic BaRuO3, 5d(4) cubic BaOsO3 was synthesized by a solid
      state reaction at a pressure of 17 GPa, and its crystal structure was
      investigated by synchrotron powder X-ray diffraction measurements. In addition,
      its magnetic susceptibility, electrical resistivity, and specific heat were
      measured over temperatures ranging from 2 to 400 K. The results establish a
      series of d(4) cubic perovskite oxides, which can help in the mapping of the
      itinerant ferromagnetism that is free from any complication from local lattice
      distortions for transitions from the 3d orbital to the 5d orbital. Such a
      perovskite series has never been synthesized at any d configuration to date.
      Although cubic BaOsO3 did not exhibit long-range ferromagnetic order unlike cubic
      BaFeO3 and BaRuO3, enhanced feature of paramagnetism was detected with weak
      temperature dependence. Orthorhombic CaOsO3 and SrOsO3 show similar magnetic
      behaviors. CaOsO3 is not as conducting as SrOsO3 and BaOsO3, presumably due to
      impact of tilting of octahedra on the width of the t2g band. These results
      elucidate the evolution of the magnetism of perovskite oxides not only in the 5d
      system but also in group 8 of the periodic table. 

PMID- 24090136
TI  - Amyotrophic lateral sclerosis-linked FUS/TLS alters stress granule assembly and
      dynamics.
AB  - BACKGROUND: Amyotrophic lateral sclerosis (ALS)-linked fused in
      sarcoma/translocated in liposarcoma (FUS/TLS or FUS) is concentrated within
      cytoplasmic stress granules under conditions of induced stress. Since only the
      mutants, but not the endogenous wild-type FUS, are associated with stress
      granules under most of the stress conditions reported to date, the relationship
      between FUS and stress granules represents a mutant-specific phenotype and thus
      may be of significance in mutant-induced pathogenesis. While the association of
      mutant-FUS with stress granules is well established, the effect of the mutant
      protein on stress granules has not been examined. Here we investigated the effect
      of mutant-FUS on stress granule formation and dynamics under conditions of
      oxidative stress. RESULTS: We found that expression of mutant-FUS delays the
      assembly of stress granules. However, once stress granules containing mutant-FUS
      are formed, they are more dynamic, larger and more abundant compared to stress
      granules lacking FUS. Once stress is removed, stress granules disassemble more
      rapidly in cells expressing mutant-FUS. These effects directly correlate with the
      degree of mutant-FUS cytoplasmic localization, which is induced by mutations in
      the nuclear localization signal of the protein. We also determine that the RGG
      domains within FUS play a key role in its association to stress granules. While
      there has been speculation that arginine methylation within these RGG domains
      modulates the incorporation of FUS into stress granules, our results demonstrate
      that this post-translational modification is not involved. CONCLUSIONS: Our
      results indicate that mutant-FUS alters the dynamic properties of stress
      granules, which is consistent with a gain-of-toxic mechanism for mutant-FUS in
      stress granule assembly and cellular stress response.

PMID- 24090138
TI  - Primary healthcare in transition--a qualitative study of how managers perceived a
      system change.
AB  - BACKGROUND: Primary healthcare in Sweden has undergone widespread reforms in
      recent years, including freedom of choice regarding provider, freedom of
      establishment and increased privatisation. The key aims of the reforms were to
      strengthen the role of the patient and improve performance in terms of access and
      responsiveness. The aim of this study was to explore how managers at publicly
      owned primary healthcare centres perceived the transition of the primary
      healthcare system and the impact it has had on their work. METHODS: In this
      qualitative study, 24 managers of publicly owned primary healthcare centres in
      the metropolitan region of Gothenburg were recruited. Semi-structured interviews
      were conducted and data were analysed using content analysis inspired by
      Silverman. RESULTS: The analysis revealed two core themes: The transition is
      perceived as a rapid change, enforced mainly through financial incentives and
      Prioritisation conflicts arise between patient groups with different needs,
      demands and levels of empowerment. The transition has produced powerful and rapid
      effects that were considered to be both positive and negative. While the new
      financial incentives were seen as a driving force and a tool for change, they
      also became a stress factor due to uncertainty, competition with other primary
      healthcare centres and negative feelings associated with staff cutbacks. The
      shift in power towards the patient improved access and service but also led to
      more patients with unreasonable demands. Managers found it difficult to
      prioritise correctly between patient groups with different needs, demands and
      levels of empowerment and they were concerned about potentially negative effects
      on less empowered patients, e.g. multi-morbid patients. Managers also experienced
      shortcomings in their change management skills. CONCLUSIONS: This qualitative
      study shows the complexity of the system change and describes the different
      effects and perceptions of the transition from a manager's perspective. This
      suggests a need for improved follow-up and control in order to monitor and govern
      system changes and ensure development towards a more effective and sustainable
      primary healthcare system.

PMID- 24090139
TI  - Physical exercise is associated with better fat mass distribution and lower
      insulin resistance in spinal cord injured individuals.
AB  - OBJECTIVES: The aim of the study was to compare total and regional body
      composition and their relationship with glucose homeostasis in physically active
      and non-active individuals with cervical spinal cord injury (c-SCI). METHODS:
      Individuals with lesion level between C5-C7 were divided into two groups:
      physically active (PA; n = 14; who practiced physical exercise for at least 3
      months, three times per week or more, minimum of 150 minutes/week): and non
      physically active (N-PA n = 8). Total fat mass (t-FM) and regional fat mass (r
      FM) were assessed by dual energy X-ray absorptiometry. Fasting plasma insulin
      (FPI) was determined by enzyme-linked immunosorbent assay. RESULTS: PA group
      present lower (P < 0.01) total fat mass (t-FM), % and kg, regional fat mass (r
      FM), % and kg, FPI levels and HOMA index, while they had higher (P < 0.001) total
      free fat mass (t-FFM), %, and regional free fat mass (r-FFM), %, compared to the
      N-PA group. In the N-PA group, FPI and HOMA index were negatively (P < 0.05)
      correlated with FFM% (r = -0.71, -0.69, respectively) and positively correlated
      to trunk-FM (r = 0.71, 0.69, respectively) and trunk-FM:t-FM (kg) ratio (r =
      0.83, 0.79, respectively). CONCLUSION: Physical exercise is associated with lower
      t-FM, r-FM, and insulin resistance, which could contribute to the decrease of the
      risk of cardiovascular and metabolic conditions in individuals with c-SCI.

PMID- 24090141
TI  - Photo-cross-linking approach to engineering small tyrosine-containing peptide
      hydrogels with enhanced mechanical stability.
AB  - Peptide-based supramolecular hydrogels have been extensively explored in
      biomaterials owing to their unique bioactive, stimulus-responsive, and
      biocompatible features. However, peptide-based hydrogels often have low
      mechanical stability with storage moduli of 10-1000 Pa. They are susceptible to
      mechanical destruction and solvent erosion, greatly hindering their practical
      application. Here, we present a photo-cross-linking strategy to enhance the
      mechanical stability of a peptide-based hydrogel by 10(4)-fold with a storage
      modulus of ~100 kPa, which is one of the highest reported so far for hydrogels
      made of small peptide molecules. This method is based on the ruthenium-complex
      catalyzed conversion of tyrosine to dityrosine upon light irradiation. The
      reinforcement of the hydrogel through photo-cross-linking can be achieved within
      2 min thanks to the fast reaction kinetics. The enhancement of the mechanical
      stability was due to the formation of a densely entangled fibrous network of
      peptide dimers through a dityrosine linkage. We showed that in order to implement
      this method successfully, the peptide sequence should be rationally designed to
      avoid the cross talk between self-assembly and cross-linking. This method is
      convenient and versatile for the enhancement of the mechanical stability of
      tyrosine-containing peptide-based hydrogels. We anticipate that the photo-cross
      linked supramolecular hydrogels with much improved mechanical stability will find
      broad applications in tissue engineering and drug controlled release.

PMID- 24090140
TI  - H3N2 canine influenza virus causes severe morbidity in dogs with induction of
      genes related to inflammation and apoptosis.
AB  - Dogs are companion animals that live in close proximity with humans. Canine H3N2
      influenza virus has been isolated from pet dogs that showed severe respiratory
      signs and other clinical symptoms such as fever, reduced body weight, and
      interstitial pneumonia. The canine H3N2 influenza virus can be highly
      transmissible among dogs via aerosols. When we analyzed global gene expression in
      the lungs of infected dogs, the genes associated with the immune response and
      cell death were greatly elevated. Taken together, our results suggest that canine
      H3N2 influenza virus can be easily transmitted among dogs, and that severe
      pneumonia in the infected dogs may be partially due to the elevated expression of
      genes related to inflammation and apoptosis. 

PMID- 24090143
TI  - Vanilla--its science of cultivation, curing, chemistry, and nutraceutical
      properties.
AB  - Vanilla is a tropical orchid belonging to the family Orchidaceae and it is mainly
      used in food, perfumery, and pharmaceutical preparations. The quality of the bean
      depends on the volatile constituent's, viz., the vanillin content, the species of
      the vine used, and the processing conditions adopted. Hence, proper pollination
      during flowering and curing by exercising utmost care are the important aspects
      of vanilla cultivation. There are different methods of curing, and each one is
      unique and named after the places of its origin like Mexican process and Bourbon
      process. Recently, Central Food Technological Research Institute, Mysore has
      developed know-how of improved curing process, where the green vanilla beans are
      cured immediately after harvest and this process takes only 32 days, which
      otherwise requires minimum of 150-180 days as reported in traditional curing
      methods. Vanillin is the most essential component of the 200 and odd such
      compounds present in vanilla beans. Vanillin as such has not shown any
      antioxidant properties, it is along with other compounds has got nutraceutical
      properties and therefore its wide usage. The medicinal future of vanilla may
      definitely lie in further research on basic science and clinical studies on the
      constituents and their mechanism of action.

PMID- 24090142
TI  - Determining the applicability of threshold of toxicological concern approaches to
      substances found in foods.
AB  - Threshold of Toxicological Concern (TTC) decision-support methods present a
      pragmatic approach to using data from well-characterized chemicals and protective
      estimates of exposure in a stepwise fashion to inform decisions regarding low
      level exposures to chemicals for which few data exist. It is based on structural
      and functional categorizations of chemicals derived from decades of animal
      testing with a wide variety of chemicals. Expertise is required to use the TTC
      methods, and there are situations in which its use is clearly inappropriate or
      not currently supported. To facilitate proper use of the TTC, this paper
      describes issues to be considered by risk managers when faced with the situation
      of an unexpected substance in food. Case studies are provided to illustrate the
      implementation of these considerations, demonstrating the steps taken in deciding
      whether it would be appropriate to apply the TTC approach in each case. By
      appropriately applying the methods, employing the appropriate scientific
      expertise, and combining use with the conservative assumptions embedded within
      the derivation of the thresholds, the TTC can realize its potential to protect
      public health and to contribute to efficient use of resources in food safety risk
      management. 

PMID- 24090144
TI  - Dried plums and their products: composition and health effects--an updated
      review.
AB  - This paper describes composition of dried plums and their products (prune juice
      and dried plum powder) with special attention to possibly bioactive compounds.
      Dried plums contain significant amounts of sorbitol, quinic acid, chlorogenic
      acids, vitamin K1, boron, copper, and potassium. Synergistic action of these and
      other compounds, which are also present in dried plums in less conspicuous
      amounts, may have beneficial health effects when dried plums are regularly
      consumed. Snacking on dried plums may increase satiety and reduce the subsequent
      intake of food, helping to control obesity, diabetes, and related cardiovascular
      diseases. Despite their sweet taste, dried plums do not cause large postprandial
      rise in blood glucose and insulin. Direct effects in the gastrointestinal tract
      include prevention of constipation and possibly colon cancer. The characteristic
      phenolic compounds and their metabolites may also act as antibacterial agents in
      both gastrointestinal and urinary tracts. The indirect salutary effects on bone
      turnover are supported by numerous laboratory studies with animals and cell
      cultures. Further investigation of phenolic compounds in dried plums,
      particularly of high molecular weight polymers, their metabolism and biological
      actions, alone and in synergy with other dried plum constituents, is necessary to
      elucidate the observed health effects and to indicate other benefits. 

PMID- 24090146
TI  - Bisphosphine-triggered one-pot sequential [3 + 2]/[3 + 2] annulation of
      allenoates with cyclic ketimines.
AB  - An efficient bisphosphine-triggered one-pot sequential [3 + 2]/[3 + 2] annulation
      of allenoates with cyclic ketimines was developed, in which the product of the
      first [3 + 2] annulation is the electron-deficient substrate for the second [3 +
      2] annulation reaction. The reaction is exceptionally regioselective and
      diastereoselective. This novel and highly convergent strategy may open up a new
      viewpoint in utilizing allenoates to prepare N-fused polycyclic compounds. 

PMID- 24090147
TI  - HLA ligandome tumor antigen discovery for personalized vaccine approach.
AB  - Every cancer is different and cancer cells differ from normal cells, in
      particular, through genetic alterations. HLA molecules on the cell surface enable
      T lymphocytes to recognize cellular alterations as antigens, including mutations,
      increase in gene product copy numbers or expression of genes usually not used in
      the adult organism. The search for cancer-associated antigens shared by many
      patients with a particular cancer has yielded a number of hits used in clinical
      vaccination trials with indication of survival benefit. Targeting cancer-specific
      antigens, which are exclusively expressed on cancer cells and not on normal
      cells, holds the promise for much better results and perhaps even a cure. Such
      antigens, however, may specifically appear in very few patients or may be mutated
      appearing just in one patient. Therefore, to target these in a molecularly
      defined way, the approach has to be individualized. 

PMID- 24090148
TI  - Community engagement in biomedical research in an African setting: the Kintampo
      Health Research Centre experience.
AB  - BACKGROUND: Community engagement (CE) is becoming relevant in health research
      activities; however, models for CE in health research are limited in developing
      countries. The Kintampo Health Research Centre (KHRC) conducts research to
      influence health policy locally and also internationally. Since its establishment
      in 1994 with the mandate of conducting relevant public health studies in the
      middle part of Ghana, KHRC has embarked on a series of clinical and operational
      studies involving community members. In these studies, community members have
      been engaged through community durbars before, during and also after all study
      implementations. Lessons learnt from these activities suggested the need to
      embark on further CE processes that could serve as a model for emerging research
      institutions based in African communities. METHODS: Interactive community
      durbars, workshops, in-depth discussions, focus group discussions and radio
      interactions were used as the main methods in the CE process. RESULTS: Community
      members outlined areas of research that they perceived as being of interest to
      them. Though community members expressed continual interest in our traditional
      areas of research in communicable, maternal, neonatal and child health, they were
      interested in new areas such as non- communicable diseases such as diabetes and
      hypertension. Misconceptions about KHRC and its research activities were
      identified and clarified. This research provided KHRC the opportunity to improve
      communication guidelines with the community and these are being used in engaging
      the community at various stages of our research, thus improving on the design and
      implementation of research. CONCLUSION: KHRC has developed a culturally
      appropriate CE model based on mutual understanding with community members. The
      experience obtained in the CE process has contributed to building CE capacity in
      KHRC. Other health research institutions in developing countries could consider
      the experiences gained.

PMID- 24090150
TI  - Anabolic steroids reduce spinal cord injury-related bone loss in rats associated
      with increased Wnt signaling.
AB  - BACKGROUND: Spinal cord injury (SCI) causes severe bone loss. At present, there
      is no practical treatment to delay or prevent bone loss in individuals with motor
      complete SCI. Hypogonadism is common in men after SCI and may exacerbate bone
      loss. The anabolic steroid nandrolone reduces bone loss due to microgravity or
      nerve transection. OBJECTIVE: To determine whether nandrolone reduced bone loss
      after SCI and, if so, to explore the mechanisms of nandrolone action. METHODS:
      Male rats with complete transection of the spinal cord were administered
      nandrolone combined with a physiological replacement dose of testosterone, or
      vehicle, beginning on day 29 after SCI and continued for 28 days. RESULTS: SCI
      reduced distal femoral and proximal tibial bone mineral density (BMD) by 25 and
      16%, respectively, at 56 days. This bone loss was attenuated by nandrolone. In ex
      vivo osteoclasts cultures, SCI increased mRNA levels for tartrate-resistant acid
      phosphatase (TRAP) and calcitonin receptor; nandrolone-normalized expression
      levels of these transcripts. In ex vivo osteoblast cultures, SCI increased
      receptor activator of NF-kB ligand (RANKL) mRNA levels but did not alter
      osteoprotegerin (OPG) mRNA expression; nandrolone-increased expression of OPG and
      OPG/RANKL ratio. SCI reduced mRNA levels of Wnt signaling-related genes Wnt3a,
      low-density lipoprotein receptor-related protein 5 (LRP5), Fzd5, Tcf7, and
      ectodermal-neural cortex 1 (ENC1) in osteoblasts, whereas nandrolone increased
      expression of each of these genes. CONCLUSIONS: The results demonstrate that
      nandrolone reduces bone loss after SCI. A potential mechanism is suggested by our
      findings wherein nandrolone modulates genes for differentiation and activity of
      osteoclasts and osteoblasts, at least in part, through the activation of Wnt
      signaling.

PMID- 24090151
TI  - Sunitinib treatment enabling resection of massive liver metastasis: a case
      report.
AB  - INTRODUCTION: Sunitinib was developed as a molecular-targeted drug to treat
      advanced renal cell carcinoma. It is not yet known whether liver damage occurs in
      patients with liver metastases of renal cell carcinoma after sunitinib
      administration. Here, we report the case of a patient with an inoperable massive
      liver metastasis of renal cell carcinoma for whom sunitinib administration was
      dramatically effective with no obvious evidence of liver damage. As a result, the
      liver metastasis could be resected. We emphasize the dramatic reduction in liver
      metastasis with sunitinib treatment, and the histopathological effects of
      sunitinib on the non-tumorous liver parenchyma. CASE PRESENTATION: A 54-year-old
      Japanese woman was diagnosed with right renal cell carcinoma and underwent right
      nephrectomy 12 years earlier. She presented to a local clinic with right
      abdominal pain. A computed tomography scan showed a massive liver metastasis
      occupying her right hepatic lobe, and she was referred to our hospital for
      treatment. The diagnosis was not only liver metastasis, but also left renal
      metastasis. Oral administration of tyrosine kinase inhibitor sunitinib was
      started. Adverse events due to sunitinib included liver dysfunction,
      thrombocytopenia, and decreased hemoglobin, but she completed eight courses with
      the help of drug holidays and dose adjustments. Post-treatment computed
      tomography showed a dramatic reduction in size of her liver metastasis, enabling
      right lobectomy of her liver. Histopathological findings showed no obvious liver
      damage due to chemotherapy in non-cancerous parenchymal areas. CONCLUSIONS: With
      the availability of sunitinib, some patients with potentially unresectable
      massive liver metastases of renal cell carcinoma may be able to undergo major
      hepatectomy curatively and safely with little histopathological damage to non
      tumorous liver parenchyma, thus improving their prognosis.

PMID- 24090154
TI  - The proteases HtrA2/Omi and UCH-L1 regulate TNF-induced necroptosis.
AB  - BACKGROUND: In apoptosis, proteolysis by caspases is the primary mechanism for
      both initiation and execution of programmed cell death (PCD). In contrast, the
      impact of proteolysis on the regulation and execution of caspase-independent
      forms of PCD (programmed necrosis, necroptosis) is only marginally understood.
      Likewise, the identity of the involved proteases has remained largely obscure.
      Here, we have investigated the impact of proteases in TNF-induced necroptosis.
      RESULTS: The serine protease inhibitor TPKC protected from TNF-induced
      necroptosis in multiple murine and human cells systems whereas inhibitors of
      metalloproteinases or calpain/cysteine and cathepsin proteases had no effect. A
      screen for proteins labeled by a fluorescent TPCK derivative in necroptotic cells
      identified HtrA2/Omi (a serine protease previously implicated in PCD) as a
      promising candidate. Demonstrating its functional impact, pharmacological
      inhibition or genetic deletion of HtrA2/Omi protected from TNF-induced
      necroptosis. Unlike in apoptosis, HtrA2/Omi did not cleave another protease,
      ubiquitin C-terminal hydrolase (UCH-L1) during TNF-induced necroptosis, but
      rather induced monoubiquitination indicative for UCH-L1 activation.
      Correspondingly, pharmacologic or RNA interference-mediated inhibition of UCH-L1
      protected from TNF-induced necroptosis. We found that UCH-L1 is a mediator of
      caspase-independent, non-apoptotic cell death also in diseased kidney podocytes
      by measuring cleavage of the protein PARP-1, caspase activity, cell death and
      cell morphology. Indicating a role of TNF in this process, podocytes with stably
      downregulated UCH-L1 proved resistant to TNF-induced necroptosis. CONCLUSIONS:
      The proteases HtrA2/Omi and UCH-L1 represent two key components of TNF-induced
      necroptosis, validating the relevance of proteolysis not only for apoptosis, but
      also for caspase-independent PCD. Since UCH-L1 clearly contributes to the non
      apoptotic death of podocytes, interference with the necroptotic properties of
      HtrA2/Omi and UCH-L1 may prove beneficial for the treatment of patients, e.g. in
      kidney failure.

PMID- 24090153
TI  - A population-based study of overweight and obesity in expectant parents: socio
      demographic patterns and within-couple associations.
AB  - BACKGROUND: Overweight and obesity in pregnancy increase the risk of several
      adverse pregnancy outcomes. However, both mothers' and fathers' health play an
      important role for long-term health outcomes in offspring. While aspects of
      health and lifestyle of pregnant women have been reported, the health of
      expectant fathers and correlations of health variables within couples have
      received less attention. This study aimed to explore the prevalence and socio
      demographic patterns of overweight and obesity in Swedish expectant parents, and
      to assess within-couple associations. METHODS: This population-based, cross
      sectional study investigated self-reported data from 4352 pregnant women and 3949
      expectant fathers, comprising 3356 identified couples. Data were collected in
      antenatal care clinics between January 2008 and December 2011. Descriptive,
      correlation and logistic regression analyses were performed. RESULTS: The self
      reported prevalence of overweight (BMI 25.0-29.99) and obesity (BMI >= 30.0) was
      29% among women (pre-pregnancy) and 53% among expectant fathers. In a majority of
      couples (62%), at least one partner was overweight or obese. The odds of being
      overweight or obese increased relative to partner's overweight or obesity, and
      women's odds of being obese were more than six times higher if their partners
      were also obese in comparison with women whose partners were of normal weight (OR
      6.2, CI 4.2-9.3). A socio-demographic gradient was found in both genders in
      relation to education, occupation and area of residence, with higher odds of
      being obese further down the social ladder. The cumulative influence of these
      factors showed a substantial increase in the odds of obesity for the least
      compared to the most privileged (OR 6.5, CI 3.6-11.8). CONCLUSIONS: The
      prevalence of overweight and obesity in expectant parents was high, with a clear
      social gradient, and a minority of couples reported both partners with a healthy
      weight at the onset of pregnancy. Partner influence on health and health
      behaviours, and the role both mothers and fathers play in health outcomes of
      their offspring, underpin the need for a more holistic and gender inclusive
      approach to the delivery of pregnancy care and postnatal and child health
      services, with active measures employed to involve fathers.

PMID- 24090155
TI  - Management of low back pain in general practice - is it of acceptable quality: an
      observational study among 25 general practices in South Tyrol (Italy).
AB  - BACKGROUND: There are several guidelines dealing with the management of low back
      pain (LBP), but only few studies on the quality of care provided within General
      Practices as judged against those guidelines.The objective of this study is to
      analyse the management of LBP in Italian General Practice and compare it with
      guideline recommendations. METHODS: In this observational study, all patients
      visiting their General Practitioners (GPs) for treatment of LBP within a 8-week
      period were monitored for at least four weeks with regard to symptoms and
      diagnostic and therapeutic interventions. Management of LBP was judged by pre
      defined quality indicators based on guideline recommendations. RESULTS: Twenty
      five of 114 eligible GPs participated in the study, representing a total of
      43,012 registered patients. Of the 475 patients complaining of LBP and monitored
      for four weeks, 55.8% were diagnosed as having acute lumbar pain, 13.5% chronic
      lumbar pain, 17.1% acute sciatica, and 12.6% chronic sciatica; 76.0% underwent no
      technical investigations, 21.7% underwent x-rays, 5.5% MRI and 4% CT scans; 20.4%
      were referred to secondary care; 93.3% of all patients received some medication.
      In those receiving a medication, in 88.3% it was an NSAID, in 6.3% Paracetamol,
      in 10.4% Paracetamol combined with Codeine, and in 9% a muscle relaxants. When
      physiotherapy was prescribed (17,1%), it was mostly massage. Hardly more than 50%
      of GPs (partially) followed locally established guidelines, while the remainder
      seemed not to follow guidelines at all. CONCLUSIONS: Our study reveals gross
      deviations of GP management of LBP from current guidelines and points to two
      different types of deviators: those who partially follow guidelines, and those
      who do not follow them at all. Further research should evaluate whether these two
      types of deviation are best addressed by different foci of education, i.e. on
      knowledge versus attitudes, respectively.

PMID- 24090156
TI  - Depression, healthcare utilization, and comorbid psychiatric disorders after
      spinal cord injury.
AB  - BACKGROUND: Depression is often comorbid with other psychiatric conditions in the
      general population, with resultant impact on severity of conditions and
      healthcare utilization. It is unclear to what degree this is also true among
      persons with spinal cord injury (SCI). OBJECTIVE: This study examined rates at
      which psychiatric conditions were comorbid with depression after SCI, and the
      association between a depression diagnosis and healthcare and pharmaceutical drug
      use. METHODS: Retrospective analysis of data (N = 41 213) abstracted from
      Veterans Health Administration administrative databases between fiscal years
      (FYs) 1997 and 2007 to examine overall rates of depression. Administrative data
      from FY 2007 was used to examine rates of psychiatric disorders comorbid with
      depression, and to compare veterans with SCI and depression to veterans with SCI
      but no depression on healthcare and pharmaceutical use. RESULTS: Twenty-eight
      percent (n = 11 506) of 41 213 veterans who received SCI care between FY 1997 and
      FY 2007 were diagnosed with depressive disorders. Among the veterans with SCI and
      depression diagnoses in 2007 (n = 2615), 70% were also diagnosed with another
      psychiatric illness, with posttraumatic stress disorder and other anxiety
      disorders being the most common. Veterans with SCI and depression had more
      healthcare visits and received more pharmaceutical prescriptions than their
      counterparts without depression. CONCLUSIONS: Persons with SCI and depression are
      likely to experience comorbid psychiatric illnesses, with associated increased
      healthcare visits and medication use. Research and theory on depression after SCI
      should develop toward describing and addressing psychiatric and medical co
      morbidities that are normative in this population.

PMID- 24090157
TI  - Enkephalin downregulation in the nucleus accumbens underlies chronic stress
      induced anhedonia.
AB  - Restraint and immobilization have been extensively used to study habituation of
      the neuroendocrine response to a repeated stressor, but behavioral consequences
      of this stress regimen remain largely uncharacterized. In this study, we used
      sucrose preference and the elevated-plus maze to probe behavioral alterations
      resulting from 14 days of restraint in rats. We observed a decrease in sucrose
      preference in stressed animals, particularly in a subgroup of individuals, but no
      alteration in anxiety behaviors (as measured in the elevated-plus maze) four days
      following the last restraint. In these low-sucrose preference animals, we
      observed a downregulation of the expression of preproenkephalin mRNA in the
      nucleus accumbens. Furthermore, we observed a strong correlation between
      enkephalin expression and sucrose preference in the shell part of the nucleus
      accumbens, with a lower level of enkephalin expression being associated with
      lower sucrose preference. Interestingly, quantification of the corticosterone
      response revealed a delayed habituation to restraint in the low-sucrose
      preference population, which suggests that vulnerability to stress-induced
      deficits might be associated with prolonged exposure to glucocorticoids. The
      induction of DeltaFosB is also reduced in the nucleus accumbens shell of the low
      sucrose preference population and this transcription factor is expressed in
      enkephalin neurons. Taken together, these results suggest that a DeltaFosB
      mediated downregulation of enkephalin in the nucleus accumbens might underlie the
      susceptibility to chronic stress. Further experiments will be needed to determine
      causality between these two phenomena.

PMID- 24090158
TI  - Molecular insights into resistance mechanisms of lepidopteran insect pests
      against toxicants.
AB  - Insect pests remain a major reason for crop loss worldwide despite extensive use
      of chemical insecticides. More than 50% of all insecticides are organophosphates,
      followed by synthetic pyrethroids, organochlorines, carbamates, and
      biopesticides, and their continued use may have many environmental, agricultural,
      medical, and socioeconomic issues. Importantly, only a countable number of
      insects have acquired the status of crop pests, mostly due to monoculture of crop
      plants and polyphagous nature of the insects. We focus on adaptations of
      Lepidopteran insects to phytochemicals and synthetic pesticides in native and
      modern agricultural systems. Because of heavy use of chemical insecticides, a
      strong selection pressure is imposed on insect populations, resulting in the
      emergence of resistance against candidate compound(s). Current knowledge suggests
      that insects generally implement a three-tier system to overcome the effect of
      toxic compounds at physiological, biochemical, and genetic levels. Furthermore,
      we have discussed whether the adaptation to phytochemicals provides an advantage
      to the insect while encountering synthetic insecticide molecules. Specific
      metabolic pathways employed by insects to convert deterrents into less toxic
      forms or their removal from the system are highlighted. Using the proteomics
      approach, insect proteins interacting with insecticides can be identified, and
      their modification in resistant insects can be characterized. Also, systems
      biology studies can offer useful cues to decipher the molecular networks
      participating in the metabolism of detrimental compounds. 

PMID- 24090161
TI  - Comparative study between different biomarkers for early prediction of
      gestational diabetes mellitus.
AB  - OBJECTIVE: To study various biomarkers in prediction of gestational diabetes
      mellitus (GDM). PATIENTS AND METHODS: Prospective observational study included
      400 pregnant women. Maternal serum sex hormone binding globulin (SHBG), high
      sensitive C-reactive protein (hs-CRP), uric acid, creatinine and albumin were
      measured before 15 weeks of gestation. Patients were followed-up for development
      of GDM. RESULTS: A total of 269 women were eligible for analysis. GDM complicated
      27 (10.03%) of pregnancies. Hs-CRP levels were significantly higher and SHBG
      levels were significantly lower among women who subsequently developed GDM
      compared with normoglycemics. Uric acid, albumin and creatinine levels were not
      significantly different between both groups. For prediction of GDM, hs-CRP at a
      cutoff value of 2.55 mg/l showed a sensitivity and a specificity of 89% and 55%,
      respectively. SHBG at a cutoff value of 211.5 nmol/l showed a sensitivity and a
      specificity of 85% and 37%, respectively. Low SHBG with high hs-CRP predicted GDM
      with a sensitivity and specificity of 74.07% and 75.62%, respectively with an
      overall accuracy of 75.46%. CONCLUSION: Hs-CRP and SHBG are important early
      predictors of GDM. Adding SHBG to hs-CRP improves specificity and serves good
      overall accuracy. Uric acid, creatinine and albumin have no role in GDM
      prediction.

PMID- 24090162
TI  - Stem-cell therapy for erectile dysfunction.
AB  - INTRODUCTION: Stem cells (SCs) have been investigated for the treatment of
      erectile dysfunction (ED). AREAS COVERED: This review covers key disease targets
      and all 33 preclinical studies, including their use of SC types, animal models,
      transplantation routes, and outcome assessment methods. EXPERT OPINION: In the
      past one and half years there have been more stem-cell-for-erectile-dysfunction
      studies than the prior 8 years combined. These new studies tend to use
      combinatory treatment approaches by modifying or supplementing SCs with
      angiogenic or neurotrophic genes or proteins. However, when considering all risks
      and benefits, these combinatory approaches do not seem more advantageous than
      single-SC approaches. Another trend is the choice of transplantation routes other
      than the standard intracavernous (IC) injection. However, with the exception of
      intravenous injection, these new transplantation approaches are more cumbersome
      than IC injection and yet offer no evidence of producing better outcomes. In
      contrast to these variations, a consensus among these studies is the suggestion
      that paracrine action, as opposed to cellular differentiation, is the principal
      therapeutic mechanism. In conclusion, IC injection of a single SC type should be
      the choice protocol for initial clinical trials, and this is clearly the case
      with two clinical trials that are currently recruiting patients.

PMID- 24090163
TI  - Age-related prevalence of low testosterone in men with spinal cord injury.
AB  - OBJECTIVE: To describe the relationship of advancing age in persons with chronic
      spinal cord injury (SCI) on the prevalence of low testosterone in men with SCI
      compared to historical normative data from able-bodied men in the general
      population. DESIGN: Retrospective, cross-sectional study. Two hundred forty-three
      healthy, non-ambulatory outpatient men with chronic SCI from age of 21 to 78
      years were included in this retrospective analysis. RESULTS: Forty-six percent of
      men with SCI were identified as having low serum total testosterone
      concentrations (total testosterone <11.3 nmol/l). The age-related decline in SCI
      for total serum testosterone concentration was 0.6%/year compared to 0.4%/year in
      the Massachusetts Male Aging Study. Between the third and eighth decade of life,
      men with SCI had a 15, 39, 50, 53, 58, and 57% prevalence rate of low serum total
      testosterone, which is higher than values reported for each decade of life for
      able-bodied men in the Baltimore Longitudinal Study on Aging. CONCLUSION:
      Compared with the general population, low serum total testosterone concentration
      occurs earlier in life in men with SCI, at a higher prevalence by decade of life,
      and their age-related decline in circulating total testosterone concentration is
      greater. Studies of T replacement therapy in men with SCI should assist in
      determining the possible functional and clinical benefits from reversing low
      serum total testosterone concentration.

PMID- 24090165
TI  - Local and average structure in zinc cyanide: toward an understanding of the
      atomistic origin of negative thermal expansion.
AB  - Neutron diffraction at 11.4 and 295 K and solid-state (67)Zn NMR are used to
      determine both the local and the average structures in the disordered, negative
      thermal expansion (NTE) material, Zn(CN)2. Solid-state NMR not only confirms that
      there is head-to-tail disorder of the C=N groups present in the solid, but yields
      information about the relative abundances of the different Zn(CN)4-n(NC)n
      tetrahedral species, which do not follow a simple binomial distribution. The
      Zn(CN)4 and Zn(NC)4 species occur with much lower probabilities than are
      predicted by binomial theory, supporting the conclusion that they are of higher
      energy than the other local arrangements. The lowest energy arrangement is
      Zn(CN)2(NC)2. The use of total neutron diffraction at 11.4 K, with analysis of
      both the Bragg diffraction and the derived total correlation function, yields the
      first experimental determination of the individual Zn-N and Zn-C bond lengths as
      1.969(2) and 2.030(2) A, respectively. The very small difference in bond lengths,
      of ~0.06 A, means that it is impossible to obtain these bond lengths using Bragg
      diffraction in isolation. Total neutron diffraction also provides information on
      both the average and the local atomic displacements responsible for NTE in
      Zn(CN)2. The principal motions giving rise to NTE are shown to be those in which
      the carbon and nitrogen atoms within individual Zn-C=N-Zn linkages are displaced
      to the same side of the Zn...Zn axis. Displacements of the carbon and nitrogen
      atoms to opposite sides of the Zn...Zn axis, suggested previously in X-ray
      studies as being responsible for NTE behavior, in fact make negligible
      contributions at temperatures up to 295 K.

PMID- 24090164
TI  - BIOCAT: a pattern recognition platform for customizable biological image
      classification and annotation.
AB  - BACKGROUND: Pattern recognition algorithms are useful in bioimage informatics
      applications such as quantifying cellular and subcellular objects, annotating
      gene expressions, and classifying phenotypes. To provide effective and efficient
      image classification and annotation for the ever-increasing microscopic images,
      it is desirable to have tools that can combine and compare various algorithms,
      and build customizable solution for different biological problems. However,
      current tools often offer a limited solution in generating user-friendly and
      extensible tools for annotating higher dimensional images that correspond to
      multiple complicated categories. RESULTS: We develop the BIOimage Classification
      and Annotation Tool (BIOCAT). It is able to apply pattern recognition algorithms
      to two- and three-dimensional biological image sets as well as regions of
      interest (ROIs) in individual images for automatic classification and annotation.
      We also propose a 3D anisotropic wavelet feature extractor for extracting
      textural features from 3D images with xy-z resolution disparity. The extractor is
      one of the about 20 built-in algorithms of feature extractors, selectors and
      classifiers in BIOCAT. The algorithms are modularized so that they can be
      "chained" in a customizable way to form adaptive solution for various problems,
      and the plugin-based extensibility gives the tool an open architecture to
      incorporate future algorithms. We have applied BIOCAT to classification and
      annotation of images and ROIs of different properties with applications in cell
      biology and neuroscience. CONCLUSIONS: BIOCAT provides a user-friendly, portable
      platform for pattern recognition based biological image classification of two-
      and three- dimensional images and ROIs. We show, via diverse case studies, that
      different algorithms and their combinations have different suitability for
      various problems. The customizability of BIOCAT is thus expected to be useful for
      providing effective and efficient solutions for a variety of biological problems
      involving image classification and annotation. We also demonstrate the
      effectiveness of 3D anisotropic wavelet in classifying both 3D image sets and
      ROIs.

PMID- 24090166
TI  - Nanoscaled surface patterns influence adhesion and growth of human dermal
      fibroblasts.
AB  - In general, there is a need for passivation of nanopatterned biomaterial surfaces
      if cells are intended to interact only with a feature of interest. For this
      reason self-assembled monolayers (SAM), varying in chain length, are used; they
      are highly effective in preventing protein adsorption or cell adhesion. In
      addition, a simple and cost-effective technique to design nanopatterns of various
      sizes and distances, the so-called nanosphere lithography (NSL), is discussed,
      which allows the control of cell adhesion and growth depending on the feature
      dimensions. Combining both techniques results in highly selective nanostructured
      surfaces, showing that single proteins selectively adsorb on activated
      nanopatterns. Additionally, adhesion and growth of normal human dermal
      fibroblasts (NHDF) is strongly affected by the nanostructure dimensions, and it
      is proven that fibronectin (FN) matrix formation of these cells is influenced,
      too. Moreover, the FN fibrils are linked to the hexagonally close-packed
      nanopatterns. As a result, the system presented here can be applied in tissue
      engineering and implant design due to the fact that the nanopattern dimensions
      give rise to further modifications and allow the introduction of chemical
      heterogeneity to guide stem cell differentiation in the future. 

PMID- 24090170
TI  - Palladium-catalyzed annulation of o-iodobiphenyls with o-bromobenzyl alcohols:
      synthesis of functionalized triphenylenes via C-C and C-H bond cleavages.
AB  - Treatment of o-iodobiphenyls with o-bromobenzyl alcohols in the presence of
      cesium carbonate under palladium catalysis affords a series of highly substituted
      triphenylenes. The reaction involves two C-C bond formations and C-C and C-H bond
      cleavages. A combination of palladium and an electron-deficient phosphine ligand
      proves to be effective for both decarbonylative cross-coupling and intramolecular
      cyclization. 

PMID- 24090168
TI  - Safety measures to prevent workplace violence in emergency primary care centres-
      a cross-sectional study.
AB  - BACKGROUND: Employees in emergency primary care centres (EPCC) have raised
      personal safety as an issue. Despite a high risk of experiencing workplace
      violence at EPCCs in Norway, knowledge regarding applied preventive measures is
      limited. The description of existing safety measures is an important prerequisite
      to evaluate and make guidelines for the improvement of preventive practices on a
      national level. The objective of this study was to investigate to which extent
      general practitioners work alone in EPCCs in Norway, and to estimate the
      prevalence of other preventive measures against workplace violence. METHODS: A
      survey was sent to the managers of all 210 registered EPCCs in Norway. The
      questionnaire included 22 items on safety measures, including available staff,
      architecture and outfitting of the reception and consulting rooms, and the
      availability of electronic safety systems and training or monitoring systems. The
      data were analysed using descriptive statistics. Differences between EPCCs
      staffed by one general practitioner alone and EPCCs with more health personnel on
      duty were explored. RESULTS: Sixty-one (30%) of the 203 participating EPCCs had
      more than one person on duty round-the-clock. These EPCCs reported the
      application of a significantly higher number of safety measures compared to the
      EPCCs with only one general practitioner on duty during some or part of the 24
      hours. Examples of safety measures being more common in highly staffed EPCCs were
      automatic door locks (p < 0.001), arrangement of furniture in the consulting room
      ensuring that the patient is not seated between the clinician and the exit (p =
      0.014), the possibility of bringing an extra person on emergency call-outs or
      home visits when needed for security reasons (p = 0.014), and having organised
      training regarding violence (p < 0.001). CONCLUSION: This study shows
      considerable differences between Norwegian EPCCs regarding applied preventive
      measures, and a higher prevalence of such measures in EPCCs staffed with several
      health personnel around-the-clock. More research is needed to understand the
      reasons for, and the effects of, these differences.

PMID- 24090172
TI  - Vaccines based on structure-based design provide protection against infectious
      diseases.
AB  - Vaccines elicit immune responses, provide protection against microorganisms and
      are considered as one of the most successful medical interventions against
      infectious diseases. Vaccines can be produced using attenuated virus or bacteria,
      recombinant proteins, bacterial polysaccharides, carbohydrates or plasmid DNA.
      Conventional vaccines rely on the induction of immune responses against antigenic
      proteins to be effective. The genetic diversity of microorganisms, coupled with
      the high degree of sequence variability in antigenic proteins, presents a
      challenge to developing broadly effective conventional vaccines. The observation
      that whole protein antigens are not necessarily essential for inducing immunity
      has led to the emergence of a new branch of vaccine design termed 'structural
      vaccinology'. Structure-based vaccines are designed on the rationale that
      protective epitopes should be sufficient to induce immune responses and provide
      protection against pathogens. Recent studies demonstrated that designing
      structure-based vaccine candidates with multiple epitopes induce a higher immune
      response. As yet there are no commercial vaccines available based on structure
      based design and most of the structure-based vaccine candidates are in the
      preclinical stages of development. This review focuses on recent advances in
      structure-based vaccine candidates and their application in providing protection
      against infectious diseases. 

PMID- 24090167
TI  - Circulating nucleic acids as biomarkers in breast cancer.
AB  - During tumor development, tumor cells release their nucleic acids into the blood
      circulation. This process occurs by apoptotic and necrotic cell deaths along with
      active cell secretion, resulting in high levels of circulating DNA, mRNA, and
      microRNA in the blood of patients with breast cancer. As circulating cell-free
      tumor nucleic acids may reflect the characteristics of the primary tumor and even
      of micrometastatic cells, they may be excellent blood biomarkers for screening
      breast cancer. Assays that allow the repetitive monitoring of patients by using
      blood samples as liquid biopsy may be efficient in assessing cancer progression
      in patients whose tumor tissue is not available. This review evaluates the recent
      data on the potential use of circulating cell-free nucleic acids as biomarkers
      for breast cancer.

PMID- 24090174
TI  - Harnessing the power of advertising to prevent childhood obesity.
AB  - BACKGROUND: Social marketing integrates communication campaigns with behavioural
      and environmental change strategies. Childhood obesity programs could benefit
      significantly from social marketing but communication campaigns on this issue
      tend to be stand-alone. METHODS: A large-scale multi-setting child obesity
      prevention program was implemented in the Hunter New England (HNE) region of New
      South Wales (NSW), Australia from 2005-2010. The program included a series of
      communication campaigns promoting the program and its key messages: drinking
      water; getting physically active and; eating more vegetables and fruit. Pre-post
      telephone surveys (n = 9) were undertaken to evaluate awareness of the campaigns
      among parents of children aged 2-15 years using repeat cross-sections of randomly
      selected cohorts. A total of 1,367 parents (HNE = 748, NSW = 619) participated.
      RESULTS: At each survey post baseline, HNE parents were significantly more likely
      to have seen, read or heard about the program and its messages in the media than
      parents in the remainder of the state (p < 0.001). Further, there was a
      significant increase in awareness of the program and each of its messages over
      time in HNE compared to no change over time in NSW (p < 0.001). Awareness was
      significantly higher (p < 0.05) in HNE compared to NSW after each specific
      campaign (except the vegetable one) and significantly higher awareness levels
      were sustained for each campaign until the end of the program. At the end of the
      program participants without a tertiary education were significantly more likely
      (p = 0.04) to be aware of the brand campaign (31%) than those with (20%) but
      there were no other statistically significant socio-demographic differences in
      awareness. CONCLUSIONS: The Good for Kids communication campaigns increased and
      maintained awareness of childhood obesity prevention messages. Moreover, messages
      were delivered equitably to diverse socio-demographic groups within the region.

PMID- 24090173
TI  - Maternal awareness of young children's physical activity: levels and cross
      sectional correlates of overestimation.
AB  - BACKGROUND: Factors associated with parental awareness of children's physical
      activity (PA) levels have not been explored in preschool-aged children. This
      paper investigates maternal awareness of preschool-aged children's PA levels and
      determined correlates associated with maternal overestimation of PA. METHODS:
      Data from the Southampton Women's Survey, a UK population-based study, were
      collected March 2006 through June 2009. Daily minutes of moderate-to-vigorous PA
      (MVPA) were derived using accelerometry in 478 4-year-old children. Mothers who
      were realistic or overestimated their child's PA were identified. Log-binomial
      regression was used to analyse correlates of maternal overestimation of PA levels
      in children whose mothers perceived them to be active (n = 438). RESULTS: 40.8%
      of children were classified as inactive: 89.7% of these were perceived to be
      active by their mothers (over-estimators). These mothers were more likely to
      think their child sometimes lacked skills required to be physically active (RR
      (95% CI) = 1.29(1.03-1.63)) and their child was more likely to attend nursery
      full-time (RR = 1.53(1.14-2.04)). They were less likely to have older children at
      home (RR = 0.71(0.56-0.90)). CONCLUSIONS: Almost 90% of mothers of inactive
      preschool-aged children perceive their child to be active. Nursery-school
      attendance and having older siblings at home may be important to consider when
      designing behavioural interventions to increase PA in preschool children.

PMID- 24090175
TI  - Linear and nonlinear quantitative structure-property relationship modelling of
      skin permeability.
AB  - In this work, quantitative structure-property relationship (QSPR) models were
      developed to estimate skin permeability based on theoretically derived molecular
      descriptors and a diverse set of experimental data. The newly developed method
      combining modified particle swarm optimization (MPSO) and multiple linear
      regression (MLR) was used to select important descriptors and develop the linear
      model using a training set of 225 compounds. The adaptive neuro-fuzzy inference
      system (ANFIS) was used as an efficient nonlinear method to correlate the
      selected descriptors with experimental skin permeability data (log Kp). The
      linear and nonlinear models were assessed by internal and external validation.
      The obtained models with three descriptors show good predictive ability for the
      test set, with coefficients of determination for the MPSO-MLR and ANFIS models
      equal to 0.874 and 0.890, respectively. The QSPR study suggests that
      hydrophobicity (encoded as log P) is the most important factor in transdermal
      penetration. 

PMID- 24090176
TI  - Unpacking personalized feedback: an exploratory study of the impact of its
      components and the reactions it elicits among problem drinking men who have sex
      with men.
AB  - Personalized feedback (PF) has demonstrated effectiveness in reducing drinking.
      Few studies have examined its effectiveness with adult problem drinkers or its
      potential mediators or moderators, including developing discrepancy. This study
      aimed to identify potential mediators and moderators of PF provided to adult
      problem drinking men who have sex with men (PDMSM). METHOD: An exploratory
      analysis of PF provided to PDMSM in the context of modified behavioral self
      control therapy (N = 90). The association of individual items of PF, severity of
      PF, and independently rated, in-session participant reactions to PF with drinking
      outcomes (mean drinks per drinking day, MDDD) were examined using correlations
      and logistic and linear regression. RESULTS: Significant pre-post differences in
      MDDD emerged. Other drug risk, family risk, and having an abnormal liver enzyme
      test result were significantly associated with proxies for developed discrepancy
      in expected directions; however, no PF item or reaction to PF predicted drinking
      outcomes. Severity of PF was not associated with participant reactions or
      drinking outcome. CONCLUSIONS: PF may be an effective intervention for PDMSM.
      Further research is needed to identify potential mediators and moderators of PF
      among adults.

PMID- 24090179
TI  - Comprehensive management of pressure ulcers in spinal cord injury: current
      concepts and future trends.
AB  - Pressure ulcers in spinal cord injury represent a challenging problem for
      patients, their caregivers, and their physicians. They often lead to recurrent
      hospitalizations, multiple surgeries, and potentially devastating complications.
      They present a significant cost to the healthcare system, they require a
      multidisciplinary team approach to manage well, and outcomes directly depend on
      patients' education, prevention, and compliance with conservative and surgical
      protocols. With so many factors involved in the successful treatment of pressure
      ulcers, an update on their comprehensive management in spinal cord injury is
      warranted. Current concepts of local wound care, surgical options, as well as
      future trends from the latest wound healing research are reviewed to aid medical
      professionals in treating patients with this difficult problem. 

PMID- 24090180
TI  - Preliminary investigation into subjective well-being, mental health, resilience,
      and spinal cord injury.
AB  - OBJECTIVES: To undertake a pilot investigation into whether individuals whose
      subjective well-being had returned to the normal homeostatic range after a spinal
      cord injury (SCI) may be more resilient and therefore, at less risk of emotional
      distress over time. To consider the relative stability of subjective well-being
      in individuals with chronic SCI whose subjective well-being had previously
      returned to the normative homeostatic range. STUDY DESIGN: Longitudinal study:
      Time 1 (T1) 2004 and Time 2 (T2) 2009. SETTING: Victoria, Australia.
      PARTICIPANTS: Participants were adults living in the community with chronic SCI,
      who had no mental ill-health symptoms at T1. OUTCOME MEASURES: Scales include:
      Comprehensive Quality of Life Scale - Adult v5 (COMQoL-A5) at T1, Personal Well
      being Index (PWI - the successor to the COMQol-A5) at T2, and Depression, Anxiety
      & Stress Scale - short form (DASS-21) at T1 and T2. RESULTS: Twenty-one adults
      participated at T1 and T2. Subjective well-being was stable for 57% of the
      cohort. However, 19% presented with symptoms of emotional distress by T2. There
      was no significant difference in age (P = 0.94) or time since injury (P = 0.51)
      between those reporting significant emotional symptoms and those without; nor was
      there any systematic change in health status. CONCLUSION: This study yielded two
      important findings. First, individuals with chronic SCI may be vulnerable to
      mental health issues even after they have previously exhibited good resilience.
      Second, subjective well-being after SCI may not be as stable as suggested by the
      general quality of life literature that have examined genetic and personality
      connections to subjective well-being.

PMID- 24090181
TI  - A case of rectal tumor in which the shape altered with regression in short
      period.
AB  - BACKGROUND: Histological regression of solid tumors in adults receiving no
      treatment is rare. Specifically, spontaneous partial and complete regression of
      colorectal cancers account for less than 2% of such cases and those without
      metastasis are exceedingly rare. CASE PRESENTATION: A 60-year-old male underwent
      total colonoscopy following a positive fecal occult blood test at the referring
      hospital. A flat elevated lesion with central reddish depression, 10 mm in
      diameter, was detected in the lower rectum. Biopsy results from the referring
      hospital showed a well-differentiated adenocarcinoma and the patient was referred
      to our hospital for diagnosis and treatment. Preoperative colonoscopy was
      performed to determine the therapeutic strategy; however, we found only scar
      tissue and there were no endoscopic features to suggest malignancy. Biopsy from
      the scar revealed normal rectal mucosa and we performed diagnostic endoscopic
      submucosal resection with a ligation device (ESMR-L) one week later. The resected
      specimen showed a 1 mm well-differentiated adenocarcinoma with low-grade atypia
      and no lymphovascular invasion. The macroscopic type was 0-IIb, the depth of
      invasion was intramucosal, and the vertical and lateral margins were negative.
      There has been no evidence of recurrence for 18 months following treatment.
      CONCLUSION: We report a case of a rectal tumor showing regression over a short
      period without treatment. Spontaneous regression of malignant tumors is a rare
      and unexplained phenomenon. Further research and understanding of the mechanism
      holds the key for treatment and prevention of cancer in the future.

PMID- 24090182
TI  - Sisyphus, the Giffen's paradox and the Holy Grail: time for organ transplantation
      to transition toward a regenerative medicine-focused type of research.

PMID- 24090183
TI  - Influence of substrate curvature on osteoblast orientation and extracellular
      matrix deposition.
AB  - BACKGROUND: The effects of microchannel diameter in hydroxyapatite (HAp)
      substrates on osteoblast behavior were investigated in this study. Microchannels
      of 100, 250 and 500 MUm diameter were created on hydroxyapatite disks. The
      changes in osteoblast precursor growth, differentiation, extra cellular matrix
      (ECM) secretion and cell attachment/orientation were investigated as a function
      of microchannel diameter. RESULTS: Curvature did not impact cellular
      differentiation, however organized cellular orientation was achieved within the
      100 and 250 MUm microchannels (mc) after 6 days compared to the 12 days it took
      for the 500mc group, while the flat substrate remained disorganized. Moreover,
      the 100, 250 and 500mc groups expressed a specific shift in orientation of 17.45
      degrees , 9.05 degrees , and 22.86 degrees  respectively in 24 days. The
      secreted/mineralized ECM showed the 100 and 250mc groups to have higher modulus
      (E) and hardness (h) (E = 42.6GPa; h = 1.6GPa) than human bone (E = 13.4-25.7GPa;
      h = 0.47-0.74GPa), which was significantly greater than the 500mc and control
      groups (p < 0.05). It was determined that substrate curvature affects the cell
      orientation, the time required for initial response, and the shift in orientation
      with time. CONCLUSIONS: These findings demonstrate the ability of osteoblasts to
      organize and mineralize differentially in microchannels similar to those found in
      the osteons of compact bone. These investigations could lead to the development
      of osteon-like scaffolds to support the regeneration of organized bone.

PMID- 24090185
TI  - Unsupervised automated high throughput phenotyping of RNAi time-lapse movies.
AB  - BACKGROUND: Gene perturbation experiments in combination with fluorescence time
      lapse cell imaging are a powerful tool in reverse genetics. High content
      applications require tools for the automated processing of the large amounts of
      data. These tools include in general several image processing steps, the
      extraction of morphological descriptors, and the grouping of cells into phenotype
      classes according to their descriptors. This phenotyping can be applied in a
      supervised or an unsupervised manner. Unsupervised methods are suitable for the
      discovery of formerly unknown phenotypes, which are expected to occur in high
      throughput RNAi time-lapse screens. RESULTS: We developed an unsupervised
      phenotyping approach based on Hidden Markov Models (HMMs) with multivariate
      Gaussian emissions for the detection of knockdown-specific phenotypes in RNAi
      time-lapse movies. The automated detection of abnormal cell morphologies allows
      us to assign a phenotypic fingerprint to each gene knockdown. By applying our
      method to the Mitocheck database, we show that a phenotypic fingerprint is
      indicative of a gene's function. CONCLUSION: Our fully unsupervised HMM-based
      phenotyping is able to automatically identify cell morphologies that are specific
      for a certain knockdown. Beyond the identification of genes whose knockdown
      affects cell morphology, phenotypic fingerprints can be used to find modules of
      functionally related genes.

PMID- 24090184
TI  - De novo design of an artificial bis[4Fe-4S] binding protein.
AB  - In nature, protein subunits containing multiple iron-sulfur clusters often
      mediate the delivery of reducing equivalents from metabolic pathways to the
      active site of redox proteins. The de novo design of redox active proteins should
      include the engineering of a conduit for the delivery of electrons to and from
      the active site, in which multiple redox active centers are arranged in a
      controlled manner. Here, we describe a designed three-helix protein, DSD-bis[4Fe
      4S], that coordinates two iron-sulfur clusters within its hydrophobic core. The
      design exploits the pseudo two-fold symmetry of the protein scaffold, DSD, which
      is a homodimeric three-helix bundle. Starting from the sequence of the parent
      peptide, we mutated eight leucine residues per dimer in the hydrophobic core to
      cysteine to provide the first coordination sphere for cubane-type iron-sulfur
      clusters. Incorporation of two clusters per dimer is readily achieved by in situ
      reconstitution and imparts increased stability to thermal denaturation compared
      to that of the apo form of the peptide as assessed by circular dichroism
      monitored thermal denaturation. The presence of [4Fe-4S] clusters in intact
      proteins is confirmed by UV-vis spectroscopy, gel filtration, analytical
      ultracentrifugation, and electron paramagnetic resonance spectroscopy. Pulsed
      electron-electron double-resonance experiments have detected a magnetic dipole
      interaction between the two clusters ~0.7 MHz, which is consistent with the
      expected intercluster distance of 29-34 A. Taken together, our data demonstrate
      the successful design of an artificial multi-iron-sulfur cluster protein with
      evidence of cluster-cluster interaction. The design principles implemented here
      can be extended to the design of multicluster molecular wires.

PMID- 24090186
TI  - Synthesis of alpha-aminonitriles with benzimidazolic and theophyllinic backbones
      using the Strecker reaction.
AB  - An example of the application of the Strecker reaction in the synthesis of a new
      class of alpha-aminonitriles with benzimidazole and theophylline backbones has
      been developed. For the synthesis of these compounds, first 4-hydroxybenzaldehyde
      was reacted with 1,3- and 1,5-dibromides/epibromohydrin to produce the
      corresponding bromo-substituted aldehydes. Then, benzimidazole/theophylline was
      reacted with the latter to generate the related benzimidazolic/theophyllinic
      aldehydes. Finally, the Strecker reactions of the synthetic benzimidazolic and
      theophyllinic aldehydes with different amines afforded the target products. 

PMID- 24090187
TI  - Enhanced CO oxidation rates at the interface of mesoporous oxides and Pt
      nanoparticles.
AB  - The interaction of the metal and support in oxide-supported transition-metal
      catalysts has been proven to have extremely favorable effects on catalytic
      performance. Herein, mesoporous Co3O4, NiO, MnO2, Fe2O3, and CeO2 were
      synthesized and utilized in CO oxidation reactions to compare the catalytic
      activities before and after loading of 2.5 nm Pt nanoparticles. Turnover
      frequencies (TOFs) of pure mesoporous oxides were 0.0002-0.015 s(-1), while
      mesoporous silica was catalytically inactive in CO oxidation. When Pt
      nanoparticles were loaded onto the oxides, the TOFs of the Pt/metal oxide systems
      (0.1-500 s(-1)) were orders of magnitude greater than those of the pure oxides or
      the silica-supported Pt nanoparticles. The catalytic activities of various
      Pt/oxide systems were further influenced by varying the ratio of CO and O2 in the
      reactant gas feed, which provided insight into the mechanism of the observed
      support effect. In situ characterization using near-edge X-ray absorption fine
      structure (NEXAFS) and ambient-pressure X-ray photoelectron spectroscopy (APXPS)
      under catalytically relevant reaction conditions demonstrated a strong
      correlation between the oxidation state of the oxide support and the catalytic
      activity at the oxide-metal interface. Through catalytic activity measurements
      and in situ X-ray spectroscopic probes, CoO, Mn3O4, and CeO2 have been identified
      as the active surface phases of the oxide at the interface with Pt nanoparticles.

PMID- 24090188
TI  - Distribution and clinical correlates of viral and host genotypes in Chinese
      patients with chronic hepatitis C virus infection.
AB  - BACKGROUND AND AIM: Chronic hepatitis C virus (HCV) infection is relatively
      frequent in China. This study investigated the clinical, demographic, and viral
      and host genetic characteristics that may influence disease manifestations and
      clinical management. METHODS: In this cross-sectional observational study,
      treatment-naive Han ethnic adults with recently confirmed chronic HCV infection
      were enrolled at 28 hospitals across China. HCV genotype and host interleukin 28B
      (IL28B) genotypes were determined and compared with patient demographic
      parameters and medical status. RESULTS: Among the 997 HCV-positive patients
      analyzed, 56.8% were infected with HCV genotype 1b, followed in prevalence by
      genotypes 2, 3, and 6, with substantial regional variation. Overall, 84.1% of
      patients were IL28B genotype CC (rs12979860), with little regional variation.
      Cirrhosis was reported in 10.1% of patients and was significantly associated with
      hepatitis B virus coinfection, low HCV viral load, low serum alanine
      aminotransferase, high serum aspartate aminotransferase, diabetes, and high
      pickled food consumption. Medical procedures were common transmission risk
      factors; however, lifestyle-associated risk factors, including intravenous drug
      abuse and tattoos or piercings, were more common in patients with HCV genotype 3
      or 6. CONCLUSIONS: Most HCV-infected Han Chinese patients were IL28B genotype CC
      (rs12979860). HCV genotypes varied by geographic region, and disease
      characteristics differed according to HCV genotype. Relatively frequent detection
      of advanced liver disease may reflect limitations on access to antiviral therapy,
      and suggests that greater awareness of factors that influence HCV-associated
      disease may help avoid clinical complications and improve patient outcomes.

PMID- 24090190
TI  - Simultaneous measurement of absorbance and quantum yields for photocurrent
      generation at dye-sensitized single-crystal ZnO electrodes.
AB  - It is often assumed that the photoresponse or incident photon-to-current
      conversion efficiency (IPCE) spectrum of a sensitized semiconductor electrode is
      directly correlated with the amount of sensitizing species present on the
      semiconductor surface. In reality, the various forms of adsorbed species, such as
      dye aggregates or dye molecules bound to different adsorption sites, such as
      terrace edges, can have significantly different electron injection yields and
      carrier recombination rates. To provide information about the amounts of the
      various adsorbed dye species and their effectiveness as sensitizers, we report
      the simultaneous acquisition of IPCE and attenuated total reflectance (ATR) UV
      vis spectra for a thiacyanine dye bound to a single-crystal oxide semiconductor
      electrode surface. ZnO single crystals were fashioned into internal-reflection
      elements to act both as a waveguide for the internally reflected probe beam for
      UV-vis spectra and as the substrate for dye sensitization using dyes with
      distinct spectral signatures for monomers and aggregates. Strong agreement was
      observed between the quantum efficiency and ATR UV-vis spectra, suggesting that,
      under the conditions employed, both monomers and aggregates of the dye studied
      generate photocurrent with the same efficiency. 

PMID- 24090189
TI  - The effect of an active implementation of a disease management programme for
      chronic obstructive pulmonary disease on healthcare utilization--a cluster
      randomised controlled trial.
AB  - BACKGROUND: The growing population living with chronic conditions calls for
      efficient healthcare-planning and effective care. Implementing disease-management
      programmes is one option for responding to this demand. Knowledge is scarce about
      the effect of implementation processes and their effect on patients; only few
      studies have reported the effectiveness of disease-management-programmes
      targeting patients with chronic obstructive pulmonary disease (COPD). The
      objective of this paper was to determine the effect on healthcare-utilization of
      an active implementation model for a disease-management-programme for patients
      with one of the major multimorbidity diseases, COPD. METHODS: The standard
      implementation of a new disease-management-programme for COPD was ongoing during
      the study-period from November 2008 to November 2010 in the Central Denmark
      Region. We wanted to test a strategy using Breakthrough Series, academic
      detailing and lists of patients with COPD. It targeted GPs and three hospitals
      serving approx. 60,000 inhabitants aged 35 or older and included interventions
      directed at professionals, organisations and patients. The study was a non
      blinded block- and cluster-randomised controlled trial with GP-practices as the
      unit of randomisation. In Ringkoebing-Skjern Municipality, Denmark, 16 GP
      practices involving 38 GPs were randomised to either the intervention-group or
      the control-group. A comparable neighbouring municipality acted as an external
      control-group which included nine GP-practices with 25 GPs. An algorithm based on
      health-registry-data on lung-related contacts to the healthcare-system identified
      2,736 patients who were alive at the end of the study-period. The population
      included in this study counted 1,372 (69.2%) patients who responded to the
      baseline questionnaire and confirmed their COPD diagnosis; 458 (33.4%) patients
      were from the intervention-group, 376 (27.4%) from the control-group and
      538(39.2%) from the external-control-group. The primary outcome was adherence to
      the disease-management-programme measured at patient-level by use of specific
      services from general practice. Secondary outcomes were use of out-of-hours
      services, outpatient-clinic, and emergency-department and hospital-admissions.
      RESULTS: The intervention practices provided more planned preventive
      consultations, additional preventive consultations and spirometries than non
      intervention practices. A comparison of the development in the intervention
      practices with the development in the control-practices showed that the
      intervention resulted in more planned preventive-consultations, fewer
      conventional consultations and fewer patients admitted without a lung-related
      diagnosis. CONCLUSIONS: Use of the active implementation model for the disease
      management-programme for COPD changed the healthcare utilization in accordance
      with the programme. TRIAL REGISTRATION: Clinicaltrials.gov identifier:
      NCT01228708.

PMID- 24090191
TI  - Zinc-mediated highly alpha-regioselective 1,4-addition of chalcones with prenyl
      bromide in THF.
AB  - alpha-Regioselective addition to chalcones was realized by use of in situ
      generated prenylzinc reagents from zinc and prenyl bromide in the presence of
      SnCl4 in a 1,4-addition fashion. The approach uses the reagent combination of
      prenyl bromide, zinc, and SnCl4 in THF, all of which are inexpensive, readily
      available, and easily removable after the reaction. 

PMID- 24090192
TI  - Therapeutic options to enhance coma arousal after traumatic brain injury: state
      of the art of current treatments to improve coma recovery.
AB  - Traumatic brain injury is a leading cause of death and disability. Optimizing the
      recovery from coma is a priority in seeking to improve patients' functional
      outcomes. Standards of care have not been established: pharmacological
      interventions, right median nerve and sensory stimulation, dorsal column
      stimulation (DCS), deep brain stimulation, transcranial magnetic stimulation,
      hyperbaric oxygen therapy and cell transplantation have all been utilized with
      contrasting results. The aim of this review is to clarify the indications for the
      various techniques and to guide the clinical practice towards an earlier coma
      arousal. A systematic bibliographic search was undertaken using the principal
      search engines (Pubmed, Embase, Ovid and Cochrane databases) to locate the most
      pertinent studies. Traumatic injury is a highly individualized process, and
      subsequent impairments are dependent on multiple factors: this heterogeneity
      influences and determines therapeutic responses to the various interventions.

PMID- 24090193
TI  - PTPRO promoter methylation is predictive of poorer outcome for HER2-positive
      breast cancer: indication for personalized therapy.
AB  - BACKGROUND: Protein Tyrosine Phosphatase Receptor-type O (PTPRO) has recently
      been in the spotlight as a tumor suppressor, whose encoding gene is frequently
      methylated in cancers. We examined the methylation status of the PTPRO gene
      promoter in breast cancer and evaluated the correlation between PTPRO promoter
      methylation and both clinicopathological parameters and prognosis of breast
      cancer patients. METHODS: Two hundred twenty-one formalin-fixed, paraffin
      embedded (FFPE) tumor tissues, 20 FFPE normal adjacent tissues and 24 matched
      plasma samples, collected from primary breast cancer patients, were assessed for
      PTPRO gene promoter methylation using methylation-specific PCR. Associations of
      promoter methylation with clinicopathological parameters were evaluated. Kaplan
      Meier survival analysis and Cox proportional hazards models were used to estimate
      the effect on survival. RESULTS: 175 samples gave identifiable PCR products, of
      which 130 cases (74.3%) had PTPRO gene promoter methylation. PTPRO methylation
      correlated with higher histological grade (P = 0.028), but not other clinical
      parameters. Multivariate analysis indicated that overall survival (OS) was
      significantly poorer in HER2-positive, but not ER-positive patients with
      methylated-PTPRO. Methylated-PTPRO was detectable in matched plasma samples and
      only observed in plasma from patients whose corresponding primary tumors were
      also methylated. CONCLUSIONS: PTPRO methylation is a common event in the primary
      breast cancer and can be reliably detected in peripheral blood samples. PTPRO
      methylation is associated with poor survival only in HER2-positive patients,
      suggesting use of PTPRO methylation as a prognostic factor for breast cancer and
      for optimizing individualized therapy for HER2-positive patients.

PMID- 24090194
TI  - Nighttime intensivist staffing and the timing of death among ICU decedents: a
      retrospective cohort study.
AB  - INTRODUCTION: Intensive care units (ICUs) are increasingly adopting 24-hour
      intensivist physician staffing. Although nighttime intensivist staffing does not
      consistently reduce mortality, it may affect other outcomes such as the quality
      of end-of-life care. METHODS: We conducted a retrospective cohort study of ICU
      decedents using the 2009-2010 Acute Physiology and Chronic Health Evaluation
      clinical information system linked to a survey of ICU staffing practices. We
      restricted the analysis to ICUs with high-intensity daytime staffing, in which
      the addition of nighttime staffing does not influence mortality. We used
      multivariable regression to assess the relationship between nighttime intensivist
      staffing and two separate outcomes potentially related to the quality of end-of
      life care: time from ICU admission to death and death at night. RESULTS: Of
      30,456 patients admitted to 27 high-intensity daytime staffed ICUs, 3,553 died in
      the hospital within 30 days. After adjustment for potential confounders,
      admission to an ICU with nighttime intensivist staffing was associated with a
      shorter duration between ICU admission and death (adjusted difference: -2.5 days,
      95% CI -3.5 to -1.5, p-value < 0.001) and a decreased odds of nighttime death
      (adjusted odds ratio: 0.75, 95% CI 0.60 to 0.94, p-value 0.011) compared to
      admission to an ICU without nighttime intensivist staffing. CONCLUSIONS: Among
      ICU decedents, nighttime intensivist staffing is associated with reduced time
      between ICU admission and death and reduced odds of nighttime death.

PMID- 24090195
TI  - Do risk perceptions explain sex differences in community integration and
      participation after Spinal Cord Injury?
AB  - OBJECTIVE: To describe how men and women with spinal cord injury (SCI) rate the
      risks posed by a set of everyday activities measured using the Risk Inventory for
      persons with Spinal Cord Injury (RISCI), and to examine whether sex differences
      are related to community integration and participation. DESIGN: Cohort study.
      SETTING: Metropolitan Detroit. PARTICIPANTS: One hundred and forty community
      dwelling white and African-American men and women with SCI. OUTCOME MEASURES:
      RISCI scores, community integration, and level of and satisfaction with community
      participation. RESULTS: Study participants were just over age 40 years, and had
      been living with SCI for 10.8 years. One-third were women and 40% were African
      American. Results showed women with SCI had higher RISCI scores (perceived more
      dangers) on every item on the RISCI Scale (P < 0.001). The items perceived to
      hold greatest risk were revealing personal information to others, going on a
      blind date, and going for a roll ("walk") alone after dark. Women with higher
      RISCI scores reported lower community integration (P < 0.05) and lower levels of
      and lower satisfaction with community participation (P < 0.01). For men, however,
      RISCI scores were mainly unrelated (except for community integration) to
      participation measures. CONCLUSION: More research is needed to determine whether
      the levels of risk perceived by women are warranted and whether a sense of
      vulnerability for women with SCI is unnecessarily limiting their chances at "a
      good life" after injury.

PMID- 24090196
TI  - CD147 promotes melanoma progression through hypoxia-induced MMP2 activation.
AB  - Hypoxia enhances MMP2 expression and the invasion and metastatic potential of
      melanoma cells. CD147 has been shown to induce MMP2 in multiple cancers. To
      investigate the role of CD147 in hypoxiainduced MMP2 activation, we performed
      immunohistochemistry (IHC) staining in 206 normal and melanoma tissue samples,
      and analyzed the correlation between HIF1alpha and CD147. ChIP (chromosome
      Immunoprecipitation) in melanoma cell lines supports that HIF1alpha directly
      binds to CD147 promoter. Moreover, we made a series of deletion mutants of CD147
      promoter, and identified a conserved HIF1alpha binding site. Point mutation in
      this site significantly decreased CD147 response to hypoxia. Importantly,
      knocking down CD147 attenuates MMP2 response to hypoxia in melanoma cell lines.
      MMP2 could not be efficiently activated by hypoxia in CD147 depletion cells.
      ELISA data showed that MMP2 secretion was reduced in CD147 depletion cells than
      control under hypoxia condition. To verify the data from cell culture model, we
      performed in vivo mouse xenograft experiment. IHC staining showed reduced MMP2
      level in CD147 depleted xenografts compared to the control group, with the
      HIF1alpha level being comparable. Our study demonstrates a novel pathway mediated
      by CD147 to promote the MMP2 activation induced by hypoxia, and helps to
      understand the interplay between hypoxia and melanoma progression. 

PMID- 24090198
TI  - Targeting CCL5 in inflammation.
AB  - INTRODUCTION: Chemokines play important roles in inflammation and in immune
      responses. This article will discuss the current literature on the C-C chemokine
      ligand 5 (CCL5), and whether it is a therapeutic target in the context of various
      allergic, autoimmune or infectious diseases. AREAS COVERED: Small-molecule
      inhibitors, chemokine and chemokine receptor-deficient mice, antibodies and
      modified chemokines are the current tools available for CCL5 research, and there
      are several ongoing clinical trials targeting the CCL5 receptors, CCR1, CCR3 and
      CCR5. There are fewer studies specifically targeting the chemokine itself and
      clinical studies with anti-CCL5 antibodies are still to be carried out. EXPERT
      OPINION: Although clinical trials are strongly biased toward HIV treatment and
      prevention with blockers of CCR5, the therapeutic potential for CCL5 and its
      receptors in other diseases is relevant. Overall, it is not likely that specific
      targeting of CCL5 will result in new adjunct strategies for the treatment of
      infectious diseases with a major inflammatory component. However, targeting CCL5
      could result in novel therapies for chronic inflammatory diseases, where it may
      decrease inflammatory responses and fibrosis, and certain solid tumors, where it
      may have a role in angiogenesis.

PMID- 24090199
TI  - Viscoelastic behavior and reinforcement mechanism in rubber nanocomposites in the
      vicinity of spherical nanoparticles.
AB  - The viscoelastic behavior and reinforcement mechanism of nano ZnO reinforced
      natural rubber (NR) nanocomposites were investigated in this study. Dynamic
      mechanical analysis was performed to investigate the nature of the constrained
      polymer region in NR-nano ZnO nanocomposites, and the constrained polymer region
      is responsible for the reinforcement mechanism. The viscoelastic and tensile
      properties of NR nanocomposites were investigated with respect to the effect of
      nanofiller loading. All the nanocomposites showed a significant increase in
      storage modulus in the glassy and rubbery regions, the shift of the tan delta
      peak to the higher temperature region, and the lowering of the tan delta peak
      intensity compared to neat NR. The enhancement in the modulus is related to the
      weight % of the added nano ZnO as well as the volume of the constrained rubber
      chains in the proximity of ZnO nanoparticles. The study of the constrained volume
      of the polymer indicates that the structure of the nanocomposite possesses a
      moderately strong interfacial interaction between rubber chains and ZnO
      nanoparticles. The type of rubber-nanofiller interaction strongly influences the
      amount and modulus of the constrained region and contributes to the enhancement
      in the storage modulus of the resulting nanocomposites. The volume fraction of
      the constrained region of the NR nanocomposites was found to have good linear
      correlation with the weight % of nano ZnO. It was also understood that there
      should exist an optimum cross-linking density for a certain nanofiller reinforced
      rubber system, as well as partial physical adsorption of macromolecular rubber
      chains on the nanofiller surface. An optimum nanofiller loading is necessary for
      moderately strong rubber-nanofiller interaction and hence for the enhancement in
      the mechanical properties of the NR nanocomposites. A core-shell morphology model
      and constrained polymer model have been proposed to explain the constrained
      polymer chains in the NR-nano ZnO nanocomposite system on the basis of these
      results. 

PMID- 24090200
TI  - Development of aldose reductase inhibitors for the treatment of inflammatory
      disorders.
AB  - INTRODUCTION: Accumulating evidence attributes a significant role to aldose
      reductase (ALR2) in the pathogenesis of several inflammatory pathologies. Aldose
      reductase inhibitors (ARIs) were found to attenuate reactive oxygen species (ROS)
      production both in vitro and in vivo. Thus, they disrupt signaling cascades that
      lead to the production of cytokines/chemokines, which induce and exacerbate
      inflammation. As a result, ARIs might hold a significant therapeutic potential as
      alternate anti-inflammatory drugs. AREAS COVERED: The authors present a
      comprehensive review of the current data that support the central role of ALR2 in
      several inflammatory pathologies (i.e., diabetes, cancer, sepsis, asthma and
      ocular inflammation). Further, the authors describe the potential underlying
      molecular mechanisms and provide a commentary on the status of ARIs in this
      field. EXPERT OPINION: It is important that future efforts focus on delineating
      all the steps of the molecular mechanism that implicates ALR2 in inflammatory
      pathologies. At the same time, utilizing the previous efforts in the field of
      ARIs, several candidates that have been proven safe in the clinic may be
      evaluated for their clinical significance as anti-inflammatory medication.
      Finally, structurally novel ARIs, designed to target specifically the
      proinflammatory subpocket of ALR2, should be pursued.

PMID- 24090197
TI  - Lentiviral vector-mediated RNA silencing in the central nervous system.
AB  - RNA silencing is an established method for investigating gene function and has
      attracted particular interest because of the potential for generating RNA-based
      therapeutics. Using lentiviral vectors as an efficient delivery system that
      offers stable, long-term expression in postmitotic cells further enhances the
      applicability of an RNA-based gene therapy for the CNS. In this review we provide
      an overview of both lentiviral vectors and RNA silencing along with design
      considerations for generating lentiviral vectors capable of RNA silencing. We go
      on to describe the current preclinical data regarding lentiviral vector-mediated
      RNA silencing for CNS disorders and discuss the concerns of side effects
      associated with lentiviral vectors and small interfering RNAs and how these might
      be mitigated.

PMID- 24090201
TI  - Combined plasma biomarkers for diagnosing mild cognition impairment and
      Alzheimer's disease.
AB  - A highly sensitive immunoassay, the immunomagnetic reduction, is used to measure
      several biomarkers for plasma that is related to Alzheimer's disease (AD). These
      biomarkers include Abeta-40, Abeta-42, and tau proteins. The samples are composed
      of four groups: healthy controls (n=66), mild cognitive impairment (MCI, n=22),
      very mild dementia (n=23), and mild-to-serve dementia, all due to AD (n=22). It
      is found that the concentrations of both Abeta-42 and tau protein for the healthy
      controls are significantly lower than those of all of the other groups. The
      sensitivity and the specificity of plasma Abeta-42 and tau protein in
      differentiating MCI from AD are all around 0.9 (0.88-0.97). However, neither
      plasma Abeta-42 nor tau-protein concentration is an adequate parameter to
      distinguish MCI from AD. A parameter is proposed, which is the product of plasma
      Abeta-42 and tau-protein levels, to differentiate MCI from AD. The sensitivity
      and specificity are found to be 0.80 and 0.82, respectively. It is concluded that
      the use of combined plasma biomarkers not only allows the differentiation of the
      healthy controls and patients with AD in both the prodromal phase and the
      dementia phase, but it also allows AD in the prodromal phase to be distinguished
      from that in the dementia phase.

PMID- 24090205
TI  - The prevalence of urinary catheterization in women and men with multiple
      sclerosis.
AB  - CONTEXT/OBJECTIVE: To determine the prevalence of urinary catheterization in
      patients with multiple sclerosis (MS). DESIGN/INTERVENTION: After obtaining
      Institutional Review Board exemption, results from the Fall 2005 North American
      Research Committee on Multiple Sclerosis (NARCOMS) survey were reviewed.
      PARTICIPANTS: Respondents to the fall 2005 NARCOMS survey. OUTCOME MEASURES:
      Responses to the Urogenital Distress Inventory (UDI-6), the Short Form-12 (SF
      12), the Patient Determined Disease Steps measure of physical disability, and
      urologic history were analyzed using descriptive statistics, the chi(2) and
      Student's t-tests, and multivariable logistic and linear regression. RESULTS: Of
      9702 (58%) responses were returned, excluding respondents with prior bladder
      surgery, 9676 participants were reviewed: primarily white (92.9%), women (75.3%),
      with average age of diagnosis of 30.2 (SD 10.0) years. Urinary catheterization
      was reported by 2514 (26%) respondents, with 1091 (11%) reporting current and
      1423 (15%) past catheter use. Among all catheter types (possibly >= 1),
      intermittent self-catheterization was most common (81%), followed by
      transurethral Foley catheterization (43%) and suprapubic catheterization (8%).
      Males were more likely to catheterize than females (32 versus 24%, P < 0.001) and
      use indwelling methods (P < 0.001). Catheterizing patients reported longer
      disease duration, greater physical disability, increased overactive bladder
      symptoms, and reduced quality of life (QoL) scores (all P < 0.001). CONCLUSIONS:
      This is the first study to demonstrate significant rates (1 in 4) of urinary
      catheterization in patients with MS. Although thought to be common, the true
      rates of catheter use among MS patient were previously unknown. Urinary
      catheterization appears to be associated with reduced QoL, increased physical
      disability and longer disease duration as well.

PMID- 24090206
TI  - A method for cell type marker discovery by high-throughput gene expression
      analysis of mixed cell populations.
AB  - BACKGROUND: Gene transcripts specifically expressed in a particular cell type
      (cell-type specific gene markers) are useful for its detection and isolation from
      a tissue or other cell mixtures. However, finding informative marker genes can be
      problematic when working with a poorly characterized cell type, as markers can
      only be unequivocally determined once the cell type has been isolated. We propose
      a method that could identify marker genes of an uncharacterized cell type within
      a mixed cell population, provided that the proportion of the cell type of
      interest in the mixture can be estimated by some indirect method, such as a
      functional assay. RESULTS: We show that cell-type specific gene markers can be
      identified from the global gene expression of several cell mixtures that contain
      the cell type of interest in a known proportion by their high correlation to the
      concentration of the corresponding cell type across the mixtures. CONCLUSIONS:
      Genes detected using this high-throughput strategy would be candidate markers
      that may be useful in detecting or purifying a cell type from a particular
      biological context. We present an experimental proof-of-concept of this method
      using cell mixtures of various well-characterized hematopoietic cell types, and
      we evaluate the performance of the method in a benchmark that explores the
      requirements and range of validity of the approach.

PMID- 24090207
TI  - Structure, function, and on-off switching of a core unit contact between CheA
      kinase and CheW adaptor protein in the bacterial chemosensory array: A disulfide
      mapping and mutagenesis study.
AB  - The ultrasensitive, ultrastable bacterial chemosensory array of Escherichia coli
      and Salmonella typhimurium is representative of the large, conserved family of
      sensory arrays that control the cellular chemotaxis of motile bacteria and
      Archaea. The core framework of the membrane-bound array is a lattice assembled
      from three components: a transmembrane receptor, a cytoplasmic His kinase (CheA),
      and a cytoplasmic adaptor protein (CheW). Structural studies in the field have
      revealed the global architecture of the array and complexes between specific
      components, but much remains to be learned about the essential protein-protein
      interfaces that define array structure and transmit signals between components.
      This study has focused on the structure, function, and on-off switching of a key
      contact between the kinase and adaptor proteins in the working, membrane-bound
      array. Specifically, the study addressed interface 1 in the putative kinase
      adaptor ring where subdomain 1 of the kinase regulatory domain contacts subdomain
      2 of the adaptor protein. Two independent approaches, disulfide mapping and site
      directed Trp and Ala mutagenesis, were employed (i) to test the structural model
      of interface 1 and (ii) to investigate its functional roles in both stable kinase
      incorporation and receptor-regulated kinase on-off switching. Studies were
      conducted in functional, membrane-bound arrays or in live cells. The findings
      reveal that crystal structures of binary and ternary complexes accurately depict
      the native interface in its kinase-activating on state. Furthermore, the findings
      indicate that at least part of the interface becomes less closely packed in its
      kinase-inhibiting off state. Together, the evidence shows the interface has a
      dual structural and signaling function that is crucial for incorporation of the
      stable kinase into the array, for kinase activation in the array on state, and
      likely for attractant-triggered kinase on-off switching. A model is presented
      that describes the concerted transmission of a conformational signal among the
      receptor, the kinase regulatory domain, and the adaptor protein. In principle,
      this signal could spread out into the surrounding array via the kinase-adaptor
      ring, employing a series of alternating frozen-dynamic transitions that transmit
      low-energy attractant signals long distances.

PMID- 24090209
TI  - Free testosterone by direct and calculated measurement versus equilibrium
      dialysis in a clinical population.
AB  - INTRODUCTION: The value of clinically available free testosterone (FT) assays
      remains controversial. Here, we evaluate the agreement between the
      radioimmunoassay (RIA) and calculated FT (cFT) versus equilibrium dialysis (EqD),
      considered the gold standard. METHODS: Fifty-six consecutive men (aged 26-77) had
      blood samples assessed for FT, including men with treated and untreated
      testosterone deficiency (TD) and men without TD. Samples were split and tested by
      the two methodologies at a Quest Diagnostics national reference laboratory. cFT
      was calculated by the Vermeulen method. RESULTS: A robust correlation was noted
      for RIA and EqD (r = 0.966) and for cFT and EqD (r = 0.986). Strong correlations
      were observed for men receiving testosterone therapy and for men in the lowest
      and highest quartiles for total and FT. The correlation of total testosterone
      with FT was similar for cFT (r = 0.843), RIA (r = 0.806), and EqD (r = 0.809).
      Sex-hormone binding globulin (SHBG) was not correlated with any measure of FT.
      Bland-Altman analysis demonstrated similar bias for both cFT and RIA, although
      cFT consistently overestimated FT. Numerical values for RIA were approximately
      one seventh of EqD values. CONCLUSIONS: These results support the clinical use of
      both RIA and cFT as measures of FT. Due to numerical differences, each test
      requires its own set of reference values.

PMID- 24090208
TI  - Body composition of women and men with complete motor paraplegia.
AB  - OBJECTIVES: To examine body composition, including the relationship between body
      mass index (BMI) and total body fat, in women and men with complete motor
      paraplegia and to make comparisons with able-bodied controls. METHODS: In 13
      subjects with traumatic, complete motor paraplegia (six women, seven men) and 39
      sex-, age-, and BMI-matched controls from the community (18 women, 21 men), we
      measured total and regional (upper extremities, trunk, and lower extremities)
      lean and fat mass using total body dual-energy X-ray absorptiometry. RESULTS:
      Both women and men with paraplegia had significantly lower lean mass in their
      lower extremities, as would be expected, and in their total body when compared
      with controls. However, they had significantly greater lean mass in their upper
      extremities than controls (4.4 kg vs. 3.6 kg, P = 0.004 and 8.6 kg vs. 6.7 kg, P
      < 0.001 in women and men, respectively); all subjects with paraplegia studied
      used manual wheelchairs. Although total body fat mass was significantly greater
      in women (P = 0.010) and men (P = <0.001) with paraplegia compared with controls,
      for the equivalent total body fat mass, BMI was actually lower in women and men
      with paraplegia than controls (e.g. 20.2 kg/m2 vs. 25.0 kg/m2, respectively).
      CONCLUSION: We report on body composition in persons with complete motor
      paraplegia, including women on whom limited information is currently available.
      Our results support the need to define better assessments of obesity in both
      women and men following spinal cord injury, particularly of central body fat
      distribution, as BMI underestimates adiposity in this population.

PMID- 24090210
TI  - Remarkable performance of Ir1/FeO(x) single-atom catalyst in water gas shift
      reaction.
AB  - High specific activity and cost effectiveness of single-atom catalysts hold
      practical value for water gas shift (WGS) reaction toward hydrogen energy. We
      reported the preparation and characterization of Ir single atoms supported on
      FeO(x) (Ir1/FeO(x)) catalysts, the activity of which is 1 order of magnitude
      higher than its cluster or nanoparticle counterparts and is even higher than
      those of the most active Au- or Pt-based catalysts. Extensive studies reveal that
      the single atoms accounted for ~70% of the total activity of catalysts containing
      single atoms, subnano clusters, and nanoparticles, thus serving as the most
      important active sites. The Ir single atoms seem to greatly enhance the
      reducibility of the FeO(x) support and generation of oxygen vacancies, leading to
      the excellent performance of the Ir1/FeO(x) single-atom catalyst. The results
      have broad implications on designing supported metal catalysts with better
      performance and lower cost.

PMID- 24090211
TI  - Fall incidents unraveled: a series of 26 video-based real-life fall events in
      three frail older persons.
AB  - BACKGROUND: For prevention and detection of falls, it is essential to unravel the
      way in which older people fall. This study aims to provide a description of video
      based real-life fall events and to examine real-life falls using the
      classification system by Noury and colleagues, which divides a fall into four
      phases (the prefall, critical, postfall and recovery phase). METHODS:
      Observational study of three older persons at high risk for falls, residing in
      assisted living or residential care facilities: a camera system was installed in
      each participant's room covering all areas, using a centralized PC platform in
      combination with standard Internet Protocol (IP) cameras. After a fall, two
      independent researchers analyzed recorded images using the camera position with
      the clearest viewpoint. RESULTS: A total of 30 falls occurred of which 26 were
      recorded on camera over 17 months. Most falls happened in the morning or evening
      (62%), when no other persons were present (88%). Participants mainly fell
      backward (initial fall direction and landing configuration) on the pelvis or
      torso and none could get up unaided. In cases where a call alarm was used (54%),
      an average of 70 seconds (SD=64; range 15-224) was needed to call for help. Staff
      responded to the call after an average of eight minutes (SD=8.4; range 2-33).
      Mean time on the ground was 28 minutes (SD=25.4; range 2-59) without using a call
      alarm compared to 11 minutes (SD=9.2; range 3-38) when using a call alarm
      (p=0.445).The real life falls were comparable with the prefall and recovery phase
      of Noury's classification system. The critical phase, however, showed a prolonged
      duration in all falls. We suggest distinguishing two separate phases: a prolonged
      loss of balance phase and the actual descending phase after failure to recover
      balance, resulting in the impact of the body on the ground. In contrast to the
      theoretical description, the postfall phase was not typically characterized by
      inactivity; this depended on the individual. CONCLUSIONS: This study contributes
      to a better understanding of the fall process in private areas of assisted living
      and residential care settings in older persons at high risk for falls.

PMID- 24090212
TI  - The role of profilin-1 in endothelial cell injury induced by advanced glycation
      end products (AGEs).
AB  - BACKGROUND: Accumulation of advanced glycation end products (AGEs) in the
      vasculature triggers a series of morphological and functional changes
      contributing to endothelial hyperpermeability. The reorganisation and
      redistribution of the cytoskeleton regulated by profilin-1 mediates endothelial
      cell contraction, which results in vascular hyperpermeability. This study aimed
      to investigate the pivotal role of profilin-1 in the process of endothelial cell
      damage induced by AGEs. METHODS: Human umbilical vein endothelial cells (HUVECs)
      were incubated with AGEs. The mRNA and protein expression of profilin-1 was
      determined using real-time PCR and western blotting analyses. The levels of
      intercellular adhesion molecule-1 (ICAM-1), nitric oxide (NO) and reactive oxygen
      species (ROS), as well as the activities of nuclear factor-kappaB (NF-kappaB) and
      protein kinase C (PKC), were detected using the appropriate kits. The levels of
      asymmetric dimethylarginine (ADMA) were determined using HPLC. The distribution
      of the cytoskeleton was visualised using immunofluorescent staining. RESULTS:
      Compared with the control, incubation of endothelial cells with AGEs (200 MUg/ml)
      for 4 or 24 h significantly up-regulated the mRNA and protein expression of
      profilin-1, markedly increased the levels of ICAM-1 and ADMA and decreased the
      production of NO (P<0.05, P<0.01), which was significantly attenuated by
      pretreatment with DPI (an antioxidant), GF 109203X (PKC inhibitor) or BAY-117082
      (NF-kappaB inhibitor). DPI (10 MUmol/L) markedly decreased the elevated levels of
      ROS induced by AGEs (200 MUg/ml, 24 h); however, GF 109203X (10 MUmol/L) and BAY
      117082 (5 MUmol/L) exhibited no significant effect on the formation of ROS by
      AGEs. Immunofluorescent staining indicated that AGEs markedly increased the
      expression of profilin-1 in the cytoplasm and the formation of actin stress
      fibres, resulting in the rearrangement and redistribution of the cytoskeleton.
      This effect was significantly ameliorated by DPI, GF 109203X, BAY-117082 or siRNA
      treatment of profilin-1. Incubation with DPI and GF 109203X markedly inhibited
      the activation of PKC triggered by AGEs, and DPI and BAY-117082 significantly
      decreased the activity of NF-kappaB mediated by AGEs. Disruption of profilin-1
      gene expression attenuated the extent of endothelial abnormalities by reducing
      ICAM-1 and ADMA levels and elevating NO levels (P<0.05, P<0.01), but this
      disruption had no effect on the activities of NF-kappaB and PKC (P>0.05).
      CONCLUSIONS: These findings suggested that profilin-1 might act as an ultimate
      and common cellular effector in the process of metabolic memory (endothelial
      abnormalities) mediated by AGEs via the ROS/PKC or ROS/NF-?B signalling pathways.

PMID- 24090213
TI  - Directional heat dissipation across the interface in anatase-rutile
      nanocomposites.
AB  - Understanding the structures and properties of interfaces in (nano-)composites
      helps to reveal their important influence on reactivity and overall performance.
      TiO2 is a technologically important material, and anatase/rutile TiO2 composites
      have been shown to display enhanced photocatalytic performance over pure anatase
      or rutile TiO2. This has been attributed to a synergistic effect between the two
      phases, but the origin of this effect as well as the structure of the interface
      has not been established. Using Raman spectroscopy, here we provide evidence of
      distinct differences in the thermal properties of the anatase and rutile moieties
      in the composite, with anatase becoming effectively much warmer than the rutile
      phase under laser irradiation. With the help of first-principles calculations, we
      analyze the atomic structure and unique electronic properties of the composite
      and infer possible reasons for the directional heat dissipation across the
      interface. 

PMID- 24090215
TI  - Exploitation of the catalytic site and 150 cavity for design of influenza A
      neuraminidase inhibitors.
AB  - We report here the exploitation of the 150 cavity in the active site of influenza
      A viral neuraminidases for the design of novel C-6 triazole-containing Tamiflu
      derivatives. A general and convenient synthetic route was developed by utilizing
      a highly substituted cyclic Baylis-Hillman acetate as an active precursor for
      azide substitution via suprafacial allylic azide [3,3]-sigmatropic rearrangement.
      Virus replication inhibitory assays in vitro of these triazole derivatives
      containing either an amino or guanidino function indicated that the guanidinium
      compound showed the higher efficacy against a strain with N2 subtype at a
      concentration of 2 * 10(-5) M but did not inhibit replication of a strain with N1
      subtype even at a concentration of 10(-4) M. In order to probe the nature of the
      enzyme-inhibitor interactions, molecular dynamics simulations were performed on
      complexes of these compounds with different neuraminidase enzymes. The results
      indicated that the candidate inhibitors occupy both the 150 cavity and catalytic
      site but with alternating occupancy. 

PMID- 24090214
TI  - Caudate resting connectivity predicts implicit probabilistic sequence learning.
AB  - Abstract Implicit probabilistic sequence learning (IPSL) involves extracting
      statistical regularities from sequences of events without awareness, and is
      thought to underlie learning of language and behavioral repertoires of everyday
      life. We examined whether resting-state functional connectivity networks of the
      caudate predicted individual differences in IPSL performance measured on a
      separate day. Whole-brain connectivity maps of a bilateral dorsal caudate (DC)
      seed were created for each subject and examined for voxelwise correlations with
      sequence learning performance, as well as with overall response speed. Higher
      learning scores (but not overall response speed) were associated with stronger
      resting-state connectivity between the DC and right medial temporal lobe, as well
      as with lower resting-state connectivity between the DC and premotor regions
      involved in motor planning. Thus, how well one learns probabilistic regularities
      without awareness is predicted by the strength of a striato-cortical network in
      the resting brain. 

PMID- 24090216
TI  - Chromosomal evolution of rDNA and H3 histone genes in representative Romaleidae
      grasshoppers from northeast Brazil.
AB  - BACKGROUND: Grasshoppers from the Romaleidae family are well distributed in the
      Neotropical Region and represent a diversified and multicolored group in which
      the karyotype is conserved. Few studies have been conducted to understand the
      evolutionary dynamics of multigene families. Here, we report the chromosomal
      locations of the 18S and 5S rDNA and H3 histone multigene families in four
      grasshopper species from the Romaleidae family, revealed by fluorescent in situ
      hybridization (FISH). RESULTS: The 5S rDNA gene was located in one or two
      chromosome pairs, depending on the species, and was found in a basal distribution
      pattern. Its chromosomal location was highly conserved among these species. The
      18S rDNA was located in a single medium-sized chromosomal pair in all species
      analyzed. Its chromosomal location was near the centromere in the proximal or
      pericentromeric regions. The location of the H3 histone gene was highly
      conserved, with slight chromosomal location differences among some species. To
      our knowledge, this is the first report of a megameric chromosome carrying both
      the chromosomal markers 18S rDNA and the H3 histone genes, thereby expanding our
      understanding of such chromosomes. CONCLUSIONS: The 5S and 18S rDNA genes and the
      H3 histone genes showed a conservative pattern in the species that we analyzed. A
      basal distribution pattern for 5S rDNA was observed with a location on the fourth
      chromosomal pair, and it was identified as the possible ancestral bearer. The 18S
      rDNA and H3 histone genes were restricted to a single pair of chromosomes,
      representing an ancestral pattern. Our results reinforce the known taxonomic
      relationships between Chromacris and Xestotrachelus, which are two close genera.

PMID- 24090218
TI  - Site-specific growth and density control of carbon nanotubes by direct deposition
      of catalytic nanoparticles generated by spark discharge.
AB  - Catalytic iron nanoparticles generated by spark discharge were used to site
      selectively grow carbon nanotubes (CNTs) and control their density. The generated
      aerosol nanoparticles were deposited on a cooled substrate by thermophoresis. The
      shadow mask on top of the cooled substrate enabled patterning of the catalytic
      nanoparticles and, thereby, patterning of CNTs synthesized by chemical vapor
      deposition. The density of CNTs could be controlled by varying the catalytic
      nanoparticle deposition time. It was also demonstrated that the density could be
      adjusted by changing the gap between the shadow mask and the substrate, taking
      advantage of the blurring effect of the deposited nanoparticles, for an identical
      deposition time. As all the processing steps for the patterned growth and density
      control of CNTs can be performed under dry conditions, we also demonstrated the
      integration of CNTs on fully processed, movable silicon microelectromechanical
      system (MEMS) structures. 

PMID- 24090217
TI  - Automated image computing reshapes computational neuroscience.
AB  - We briefly identify several critical issues in current computational
      neuroscience, and present our opinions on potential solutions based on bioimage
      informatics, especially automated image computing. 

PMID- 24090219
TI  - Novel approaches in antimalarial drug discovery.
AB  - INTRODUCTION: The development of new antimalarial drugs remains of the utmost
      importance, since Plasmodium falciparum has developed resistance against nearly
      all chemotherapeutics in clinical use. In an effort to contain the resistance of
      P. falciparum against artemisinins and to further eradication efforts, studies
      are ongoing to identify novel and more efficacious approaches to develop
      antimalarials. AREAS COVERED: The authors review the classical and new approaches
      to antimalarial drug discovery, with a special emphasis on the various stages of
      the parasite's life cycle and the different Plasmodium species. The authors
      discuss the methodologies and strategies for early efficacy testing that aim to
      narrow down the portfolio of promising compounds. EXPERT OPINION: The increased
      efforts in the discovery and development of new antimalarial compounds have led
      to the recognition of new promising hits. However, there is still major roadblock
      of selecting the most promising compounds and then further testing them in early
      clinical trials, especially in the current restricted economy. Controlled human
      malaria infection has much potential for speeding-up the early development
      process of many drug candidates including those which target the pre-erythrocytic
      stages.

PMID- 24090222
TI  - Directional cloning of DNA fragments using deoxyinosine-containing
      oligonucleotides and endonuclease V.
AB  - BACKGROUND: DNA fragments carrying internal recognition sites for the restriction
      endonucleases intended for cloning into a target plasmid pose a challenge for
      conventional cloning. RESULTS: A method for directional insertion of DNA
      fragments into plasmid vectors has been developed. The target sequence is
      amplified from a template DNA sample by PCR using two oligonucleotides each
      containing a single deoxyinosine base at the third position from the 5' end.
      Treatment of such PCR products with endonuclease V generates 3' protruding ends
      suitable for ligation with vector fragments created by conventional restriction
      endonuclease reactions. CONCLUSIONS: The developed approach generates terminal
      cohesive ends without the use of Type II restriction endonucleases, and is thus
      independent from the DNA sequence. Due to PCR amplification, minimal amounts of
      template DNA are required. Using the robust Taq enzyme or a proofreading Pfu DNA
      polymerase mutant, the method is applicable to a broad range of insert sequences.
      Appropriate primer design enables direct incorporation of terminal DNA sequence
      modifications such as tag addition, insertions, deletions and mutations into the
      cloning strategy. Further, the restriction sites of the target plasmid can be
      either retained or removed.

PMID- 24090223
TI  - Development of thiophenic analogues of benzothiadiazine dioxides as new powerful
      potentiators of 2-amino-3-(3-hydroxy-5-methylisoxazol-4-yl)propionic acid (AMPA)
      receptors.
AB  - On the basis of the results obtained in previous series of AMPA potentiators
      belonging to 3,4-dihydro-2H-benzo- and 3,4-dihydro-2H-pyrido-1,2,4-thiadiazine
      1,1-dioxides, the present work focuses on the design of original isosteric 3,4
      dihydro-2H-thieno-1,2,4-thiadiazine 1,1-dioxides. Owing to the sulfur position,
      three series of compounds were developed and their activity as AMPA potentiators
      was characterized. In each of the developed series, potent compounds were
      discovered. After screening the selected active compounds on a safety in vivo
      test, 6-chloro-4-ethyl-3,4-dihydro-2H-thieno[2,3-e]-1,2,4-thiadiazine 1,1-dioxide
      (24) appeared as the most promising compound and was further evaluated. Its
      effects on long-term potentiation in vivo and on AMPA-mediated noradrenaline
      release were measured to predict its potential cognitive enhancing properties.
      Finally, an object recognition test performed in mice revealed that 24 was able
      to significantly enhance cognition, after oral administration, at doses as low as
      0.3 mg/kg. This study validates the interest of the isosteric replacement of the
      benzene or pyridine nuclei by the thiophene nucleus in the ring-fused thiadiazine
      dioxides class of AMPA potentiators. 

PMID- 24090224
TI  - Comment and reply on: emerging role of Th22 and IL-22 in multiple sclerosis, an
      autoimmune disease in the central nervous system.

PMID- 24090225
TI  - Lead exposure is a risk for worsening bone mineral density in middle-aged male
      workers.
AB  - OBJECTIVE: Lead exposure linked to osteoporosis in women. However, there is no
      direct evidence whether lead exposure has effects on bone metabolism in middle
      aged male subjects. Therefore, the present study investigated the relationship
      between bone mineral densitometry measurements, bone markers, endocrine hormones
      and blood lead levels. MATERIAL AND METHODS: The present study included lead
      exposure patients (n: 30) and control subjects (n: 32). We recorded information
      on patient demographics and risk factors of osteoporosis. Blood lead levels were
      evaluated using Varian AA 240Z atomic absorption spectrophotometry. Bone mineral
      density measurements were measured using dual-energy X-ray absorptiometry.
      RESULTS: Each lumbar T and Z scores in the lead exposure group were lower than
      the control group. There were no significant differences in femur neck and femur
      total T and Z scores between two groups. Blood lead levels were also negatively
      correlated with lumbar 2-4 T score, total lumbar T score, lumbar 2-4 Z score and
      total lumbar Z score. Urinary hydroxyproline and urinary deoxypyridinoline levels
      in the lead exposure group were significantly higher compared to controls. Blood
      lead levels were strong, positively correlated with urinary deoxypyridinoline.
      Endocrine hormone levels and 1,25-dihydroxy-vitamin D3 levels were comparable
      between lead exposure and control group. CONCLUSION: Lead exposure in male
      workers is an important factor for deterioration in bone mineral density. We
      should be screening blood lead levels and history of lead exposure in male
      osteoporosis.

PMID- 24090226
TI  - Stereocontrolled first total syntheses of amarouciaxanthin A and B.
AB  - The first total syntheses of amarouciaxanthin A and B (C40) via the
      stereoselective Wittig reaction of C15-allenic and C15-acetylenic tri-n
      butylphosphonium salts with the unprecedented C25-3,8-dihydroxy-5,6
      epoxyapocarotenal have been completed. Oxidation of the two hydroxyl groups in
      the left part of the resulting condensation products followed by regioselective
      oxirane ring opening gave the target carotenoids. 

PMID- 24090227
TI  - Dorsal column myelopathy following intrathecal chemotherapy for acute
      lymphoblastic leukemia.
AB  - OBJECTIVE/CONTEXT: To describe a distinctive clinical and radiographic pattern of
      myelopathy following intrathecal chemotherapy. Myelopathy is a rare complication
      of intrathecal chemotherapy used in the treatment of acute lymphoblastic leukemia
      (ALL). We present a 42-year-old female with T-cell ALL who developed a myelopathy
      primarily involving the dorsal columns. METHOD: Case report and literature
      review. FINDINGS: Within 24 hours of an injection of intrathecal methotrexate,
      cytarabine, and hydrocortisone, the patient developed ascending lower limb
      numbness and balance difficulties progressing to the inability to ambulate.
      Clinical examination showed profound loss of lower limb proprioception and light
      touch sensation below T5, mild proximal limb weakness, but preserved pinprick and
      temperature sensation with intact bowel and bladder function. Initial thoracic
      and lumbar spine magnetic resonance imaging (MRI) at 1 week revealed no
      abnormalities. However, repeat imaging at 6 weeks showed abnormal signal in the
      posterior cord with sparing of the anterior and lateral columns, diffusely
      involving the lower cervical cord through the conus medullaris. Dermatomal
      somatosensory-evoked potential (DSEP) conduction abnormalities were consistent
      with thoracic myelopathy. An empiric trial of high-dose intravenous
      corticosteroids during inpatient rehabilitation more than 6 weeks later produced
      no significant clinical improvement. CONCLUSION/CLINICAL RELEVANCE: Preferential
      and persistent dorsal column myelopathy is a distinctive clinical and
      radiographic presentation of a rare complication of intrathecal chemotherapy. The
      MRI abnormalities were initially absent, but evolved to consist of multi-level
      spinal cord T2 and STIR hyperintensity with regional gadolinium enhancement.
      DSEPs more accurately reflected the clinical level of spinal cord dysfunction.

PMID- 24090229
TI  - Variability in protocols on donation after circulatory death in Europe.
AB  - INTRODUCTION: Organ donation after circulatory death (DCD) has become an accepted
      strategy to reduce the shortage of organs for transplantation in many European
      countries. The use and number of DCD donors varies between countries. The purpose
      of this study was to evaluate the available protocols for DCD in Europe. METHODS:
      We contacted national transplant societies and responsible transplant co
      ordinators in the countries that perform DCD to obtain DCD protocols. We compared
      information on the protocols and additional data including: inclusion and
      exclusion criteria for donation, legislation, determination of death and
      preservation methods. RESULTS: In ten European countries DCD is performed, eight
      of which describe the methods in protocols. There are large differences in used
      DCD categories, legislation and the way death is determined. Protocols differ in
      the detail in which DCD procedures are described and the way methods are
      supported by additional consensus statements and ethical frameworks. CONCLUSIONS:
      Although DCD is an established strategy to enlarge the donor pool and to
      contribute to the reduction of the waiting list for transplantation, its
      potential has not been fully utilized yet. To further promote DCD
      transplantation, it is important to share expertise and obtain consensus, so that
      this can be translated into more uniform and solid protocols supported by the
      competent authorities, transplant and intensive care professionals, which may
      eventually result in a further promotion of DCD transplantation in Europe.

PMID- 24090228
TI  - A randomized controlled trial of venlafaxine XR for major depressive disorder
      after spinal cord injury: Methods and lessons learned.
AB  - CONTEXT/OBJECTIVE: We describe the rationale, design, methods, and lessons
      learned conducting a treatment trial for major depressive disorder (MDD) or
      dysthymia in people with spinal cord injury (SCI). DESIGN: A multi-site, double
      blind, randomized (1:1) placebo controlled trial of venlafaxine XR for MDD or
      dysthymia. Subjects were block randomized and stratified by site, lifetime
      history of substance dependence, and prior history of MDD. SETTING: Six SCI
      centers throughout the United States. PARTICIPANTS: Across participating centers,
      2536 subjects were screened and 133 were enrolled into the trial. Subjects were
      18-64 years old and at least 1 month post-SCI. Interventions Twelve-week trial of
      venlafaxine XR versus placebo using a flexible titration schedule. OUTCOME
      MEASURES: The primary outcome was improvement in depression severity at 12 weeks.
      The secondary outcome was improvement in pain. RESULTS: This article includes
      study methods, modifications prompted by a formative review process, preliminary
      data on the study sample and lessons learned. We describe common methodological
      and operational challenges conducting multi-site trials and how we addressed
      them. Challenges included study organization and decision making, staff training,
      obtaining human subjects approval, standardization of measurement and treatment,
      data and safety monitoring, subject screening and recruitment, unblinding and
      continuity of care, database management, and data analysis. CONCLUSIONS: The
      methodological and operational challenges we faced and the lessons we learned may
      provide useful information for researchers who aim to conduct clinical trials,
      especially in the area of medical treatment of depression in people with SCI.

PMID- 24090230
TI  - Detection of a substantial number of sub-microscopic Plasmodium falciparum
      infections by polymerase chain reaction: a potential threat to malaria control
      and diagnosis in Ethiopia.
AB  - BACKGROUND: Prompt and effective malaria diagnosis not only alleviates individual
      suffering, but also decreases malaria transmission at the community level. The
      commonly used diagnostic methods, microscopy and rapid diagnostic tests, are
      usually insensitive at very low-density parasitaemia. Molecular techniques, on
      the other hand, allow the detection of low-level, sub-microscopic parasitaemia.
      This study aimed to explore the presence of sub-microscopic Plasmodium falciparum
      infections using polymerase chain reaction (PCR). The PCR-based parasite
      prevalence was compared against microscopy and rapid diagnostic test (RDT).
      METHODS: This study used 1,453 blood samples collected from clinical patients and
      sub-clinical subjects to determine the prevalence of sub-microscopic P.
      falciparum carriages. Subsets of RDT and microscopy negative blood samples were
      tested by PCR while all RDT and microscopically confirmed P. falciparum-infected
      samples were subjected to PCR. Finger-prick blood samples spotted on filter paper
      were used for parasite genomic DNA extraction. RESULTS: The prevalence of sub
      microscopic P. falciparum carriage was 19.2% (77/400) (95% CI = 15. 4-23.1).
      Microscopy-based prevalence of P. falciparum infection was 3.7% (54/1,453) while
      the prevalence was 6.9% (100/1,453) using RDT alone. Using microscopy and PCR,
      the estimated parasite prevalence was 20.6% if PCR were performed in 1,453 blood
      samples. The prevalence was estimated to be 22.7% if RDT and PCR were used. Of 54
      microscopically confirmed P. falciparum-infected subjects, PCR detected 90.7%
      (49/54). Out of 100 RDT-confirmed P. falciparum infections; PCR detected 80.0%
      (80/100). The sensitivity of PCR relative to microscopy and RDT was, therefore,
      90.7% and 80%, respectively. The sensitivity of microscopy and RDT relative to
      PCR was 16.5 (49/299) and 24.2% (80/330), respectively. The overall PCR-based
      prevalence of P. falciparum infection was 5.6- and 3.3 fold higher than that
      determined by microscopy and RDT, respectively. None of the sub-microscopic
      subjects had severe anaemia, though 29.4% had mild anaemia (10-11.9 g/dl).
      CONCLUSIONS: Asymptomatic, low-density malaria infection was common in the study
      area and PCR may be a better tool for measuring Plasmodium prevalence than
      microscopy and RDT. The inadequate sensitivity of the diagnostic methods to
      detect substantial number of sub-microscopic parasitaemia would undoubtedly
      affect malaria control efforts, making reduction of transmission more difficult.
      RDT and microscopy-based prevalence studies and subsequent reports of reduction
      in malaria incidence underestimate the true pictures of P. falciparum infections
      in the community. PCR, on the other hand, seems to have reasonable sensitivity to
      detect a higher number of infected subjects with low and sub-microscopic parasite
      densities than RDTs or microscopy.

PMID- 24090231
TI  - Intracellular pH-sensitive PEG-block-acetalated-dextrans as efficient drug
      delivery platforms.
AB  - Intracellular pH-sensitive micelles of PEG-block-acetalated-dextran (PEG-b-AC
      Dex) were prepared and used for acid-triggered intracellular release of
      anticancer drug. The hydrodynamic radii (Rh) of PEG-b-AC-Dex micelles could
      increase after incubation in PBS solution at pH 5.5. Based on the pH-responsive
      Rh variation behavior, it was expected that the PEG-b-AC-Dex micelles should be
      interesting for intracellular drug delivery. Thus, doxorubicin (DOX), a wide
      spectrum anticancer drug, was loaded into the micelles and the pH-dependent
      release of the payload DOX was tested in vitro. The in vitro drug release
      profiles showed that only a small amount of the loaded DOX was released in PBS
      solution at pH 7.4, while up to about 90% of the loaded DOX could be quickly
      released in PBS solution at pH 5.5. Compared to pH-insensitive PEG-PLA micelles,
      the PEG-b-AC-Dex micelles displayed a faster drug release behavior in tumor
      cells. Moreover, higher cellular proliferation inhibition efficacy was achieved
      toward tumor cells. These features suggested that DOX could be efficiently loaded
      and delivered into tumor cells in vitro by the intracelluar pH-sensitive
      micelles, leading to enhanced inhibition of tumor cell proliferation. Therefore,
      the pH-sensitive micelles may provide a promising carrier for acid-triggered drug
      release for cancer therapy. 

PMID- 24090233
TI  - Online electrochemical monitoring of dynamic change of hippocampal ascorbate:
      toward a platform for in vivo evaluation of antioxidant neuroprotective
      efficiency against cerebral ischemia injury.
AB  - Effective monitoring of cerebral ascorbate following intravenous antioxidant
      treatment is of great importance in evaluating the antioxidant efficiency for
      neuroprotection because ascorbate is closely related to a series of ischemia
      induced neuropathological processes. This study demonstrates the validity of an
      online electrochemical system (OECS) for ascorbate detection as a platform for in
      vivo evaluation of neuroprotective efficiency of antioxidants by studying the
      dynamic change of hippocampal ascorbate during the acute period of cerebral
      ischemia and its responses to intravenous administration of antioxidants
      including ascorbate and glutathione (GSH). The OECS consists of a selective
      electrochemical detector made of a thin-layer electrochemical flow cell
      integrated with in vivo microdialysis. With such a system, the basal level of
      hippocampal ascorbate is determined to be 5.18 +/- 0.60 MUM (n = 20). This level
      is increased by 10 min of two-vessel occlusion (2-VO) ischemia treatment and
      reaches 11.51 +/- 3.43 MUM (n = 5) at the time point of 60 min after the
      ischemia. The 2-VO ischemia-induced hippocampal ascorbate increase is obviously
      attenuated by immediate intravenous administration of ascorbate (2.94 g/kg) or
      glutathione (5.12 g/kg) within 10 min after ischemia and the ascorbate level
      remains to be 3.75 +/- 1.66 MUM (n = 4) and 5.30 +/- 0.79 MUM (n = 5),
      respectively, at the time point of 60 min after ischemia. To confirm if the
      attenuated hippocampal ascorbate increase is attributed to the antioxidant
      induced oxidative stress alleviation, we further study the immunoreactivity of 8
      hydroxy-2-deoxyguanosine (8-OHdG) in the ischemic hippocampus and find that the 8
      OHdG immunoreactivity is decreased by the administration of ascorbate or GSH as
      compared to the ischemic brain without antioxidant treatment. These results
      substantially demonstrate that the OECS for ascorbate detection could be
      potentially used as a platform for evaluating the efficiency of antioxidant
      neuroprotection in cerebral ischemia treatment. 

PMID- 24090234
TI  - Nucleophilic substitution of azide acting as a pseudo leaving group: one-step
      synthesis of various aza heterocycles.
AB  - The reaction of 3-azidopropanoic acid with the carbodiimide-based coupling
      reagent DIC leads to a six-membered-ring intermediate acting as a versatile
      precursor to a diverse set of aza heterocycles, including mono-, bi-, and
      tricyclic compounds. 

PMID- 24090235
TI  - High-pressure synthesis and characterization of Li2Ca3[N2]3--an uncommon metallic
      diazenide with [N2]2- ions.
AB  - Dinitrogen (N2) ligation is a common and well-characterized structural motif in
      bioinorganic synthesis. In solid-state chemistry, on the other hand, homonuclear
      dinitrogen entities as structural building units proved existence only very
      recently. High-pressure/high-temperature (HP/HT) syntheses have afforded a number
      of binary diazenides and pernitrides with [N2](2-) and [N2](4-) ions,
      respectively. Here, we report on the HP/HT synthesis of the first ternary
      diazenide. Li2Ca3[N2]3 (space group Pmma, no. 51, a = 4.7747(1), b = 13.9792(4),
      c = 8.0718(4) A, Z = 4, wRp = 0.08109) was synthesized by controlled thermal
      decomposition of a stoichiometric mixture of lithium azide and calcium azide in a
      multianvil device under a pressure of 9 GPa at 1023 K. Powder X-ray diffraction
      analysis reveals strongly elongated N-N bond lengths of dNN = 1.34(2)-1.35(3) A
      exceeding those of previously known, binary diazenides. In fact, the refined N-N
      distances in Li2Ca3[N2]3 would rather suggest the presence of [N2](3.-) radical
      ions. Also, characteristic features of the N-N stretching vibration occur at
      lower wavenumbers (1260-1020 cm(-1)) than in the binary phases, and these
      assignments are supported by first-principles phonon calculations. Ultimately,
      the true character of the N2 entity in Li2Ca3[N2]3 is probed by a variety of
      complementary techniques, including electron diffraction, electron spin resonance
      spectroscopy (ESR), magnetic and electric conductivity measurements, as well as
      density-functional theory calculations (DFT). Unequivocally, the title compound
      is shown to be metallic containing diazenide [N2](2-) units according to the
      formula (Li(+))2(Ca(2+))3([N2](2-))3.(e(-))2.

PMID- 24090236
TI  - The multidimensional scale of perceived social support: analyses of internal
      reliability, measurement invariance, and correlates across gender.
AB  - In this study, we examined estimates of internal consistency reliability,
      measurement invariance, and differential correlates of the Multidimensional Scale
      of Perceived Social Support (MSPSS; Zimet, Dahlem, Zimet, & Farley, 1988) in
      samples of undergraduate men (n = 270) and women (n = 340). The MSPSS is designed
      to assess 3 sources of perceived social support: family, friends, and significant
      others. The participants ranged in age from 18 to 24 years (M(age) = 19.60, SD =
      1.4 years). First, composite scale reliability and coefficient omega methods
      provided adequate estimates of internal consistency reliability for the original
      MSPSS total and subscale scores. Second, results of multiple-groups invariance
      confirmatory factor analysis provided support for configural and metric
      invariance. Partial measurement invariance was attained for scalar and strict
      measurement invariance across men and women. Additionally, given the high
      correlations among the first-order factors, we conducted multiple-groups bifactor
      item response theory (bifactor-IRT) analysis to evaluate further the performances
      of the individual MSPSS items across gender. Support for the bifactor model was
      strong. Third, we conducted a series of simultaneous regression analyses to
      identify potential correlates of the social support construct for women and men.

PMID- 24090237
TI  - Pilot study comparing the two hemostatic agents in patients undergoing partial
      nephrectomy.
AB  - BACKGROUND: Recently studies have demonstrated improved outcomes in patients
      undergoing nephron-sparing surgery (NSS) for low stage renal tumors, thus NSS is
      widely accepted as the treatment option for these patients. With NSS, there is a
      risk of renal hemorrhage and thus haemostatic agents may be routinely applied to
      the cut surface of the kidney. Herein we compare two commercially available
      haemostatic agents applied intra-operatively to the cut surface of the kidney.
      Post-operative outcomes (oncologic and non-oncologic) are reported. METHODS: The
      medical records of 23 patients with suspicious renal mass documented on axial
      imaging and who underwent open NSS via a mini-subcostal incision were extensively
      reviewed. One of two haemostatic agents (Floseal(r), n = 11; Arista(r), n = 12)
      was intra-operatively applied to the cut surface of the kidney. Chi-square and T-
      student test was used to compare outcomes between the cohort of 11 patients who
      had Floseal(r) and the 12 patients who had Arista(r). RESULTS: Median pre
      operative size of renal mass was 4.3 cm (range 1.5-7.0 cm). Final pathology
      revealed 3 oncocytomas and 20 renal cell carcinoma (17 clear cell, 1 chromophobe
      and 2 papillary), pT1a = 14 and pT1b = 6. Mean intra-operative blood loss and
      hospital stay between the Floseal(r)vs. Arista(r) cohorts did not significantly
      differ (227 mL vs. 250 mL, p = 0.68 and 4.4 days vs. 4.5 days, p = 0.76,
      respectively). Intra-operative and post-operative complications were not
      different between the two cohorts. No recurrences have been documented with a
      mean follow-up of 18 months. CONCLUSION: Along with meticulous surgical
      technique, the use of either haemostatic agent (Floseal(r) or Arista(r)) was not
      associated with high rate of intra-operative or post-operative haemorrhage. Thus
      either haemostatic agent may be successfully used during NSS.

PMID- 24090239
TI  - Polyethylenimine and chitosan carriers for the delivery of RNA interference
      effectors.
AB  - INTRODUCTION: Manipulating gene activity represents a promising approach for the
      treatment of cancer and other diseases. The relatively recent discovery of RNA
      interference (RNAi) revolutionized therapeutic approaches in this field. RNA
      effectors can now be used to modify the activity of genes and theoretically
      control any biological process. AREA COVERED: However, the clinical application
      of RNAi has been limited by the inefficient delivery of RNA. Challenges
      associated with the in vivo use of RNAi mediators, include rapid degradation,
      uptake by the reticular endothelial system and inefficient cellular
      internalization. To date, various strategies have been developed in order to
      overcome these pitfalls. Among these approaches, non-viral delivery systems have
      gained increasing popularity, as they are generally considered safer than their
      viral counterparts. EXPERT OPINION: The use of cationic polymers, especially
      polyethylenimine and chitosan, for the in vivo delivery of doubled-stranded RNAs
      is discussed in this review.

PMID- 24090238
TI  - Identifying and classifying quality-of-life tools for assessing pressure ulcers
      after spinal cord injury.
AB  - CONTEXT: Although pressure ulcers may negatively influence quality of life (QoL)
      post-spinal cord injury (SCI), our understanding of how to assess their impact is
      confounded by conceptual and measurement issues. To ensure that descriptions of
      pressure ulcer impact are appropriately characterized, measures should be
      selected according to the domains that they evaluate and the population and
      pathologies for which they are designed. OBJECTIVE: To conduct a systematic
      literature review to identify and classify outcome measures used to assess the
      impact of pressure ulcers on QoL after SCI. METHODS: Electronic databases
      (Medline/PubMed, CINAHL, and PsycInfo) were searched for studies published
      between 1975 and 2011. Identified outcome measures were classified as being
      either subjective or objective using a QoL model. RESULTS: Fourteen studies were
      identified. The majority of tools identified in these studies did not have
      psychometric evidence supporting their use in the SCI population with the
      exception of two objective measures, the Short-Form 36 and the Craig Handicap
      Assessment and Reporting Technique, and two subjective measures, the Life
      Situation Questionnaire-Revised and the Ferrans and Powers Quality of Life Index
      SCI-Version. CONCLUSION: Many QoL outcome tools showed promise in being sensitive
      to the presence of pressure ulcers, but few of them have been validated for use
      with SCI. Prospective studies should employ more rigorous methods for collecting
      data on pressure ulcer severity and location to improve the quality of findings
      with regard to their impact on QoL. The Cardiff Wound Impact Schedule is a
      potential tool for assessing impact of pressure ulcers-post SCI.

PMID- 24090240
TI  - Liver stem cells: from preface to advancements.
AB  - Liver is a major metabolic organ of the body and is known to comprise of two
      epithelial cell lineages, namely, hepatocytes and cholangiocytes which are known
      to originate from hepatoblasts during fetal developing stages. Upon acute injury,
      the hepatocytes and cholangiocytes undergo cellular division to compensate the
      loss, however, chronic damage may suppress this proliferative ability and as a
      consequence hepatic and extra-hepatic stem cells may contribute for liver
      regeneration. Facultative liver stem cells (oval cells) may emerge, proliferate
      and contribute in replacing damaged hepatic cells. Similarly, bone marrow and
      mesenchymal stem cells are also known for contributing in liver regeneration
      having their ability of self renewal and differentiation. However, a closer look
      is still required to bridge the existing knowledge gaps between functionality and
      limitations. Thereby, we have discussed the detailed mechanistic insights of both
      hepatic and extra-hepatic stem cells including, stem/progenitor cells,
      adult/fetal hepatocytes, oval cells, bone marrow and mesenchymal stem cells. We
      have also focused on few in vitro and in vivo studies elucidating therapeutic
      applications and challenges related to the liver stem cells. We believe that such
      conversations may provide invaluable contribution for realistic advancement in
      the state of therapeutic stem-cell transplantation. 

PMID- 24090244
TI  - Synechocystis sp. PCC6803 metabolic models for the enhanced production of
      hydrogen.
AB  - In the present economy, difficulties to access energy sources are real drawbacks
      to maintain our current lifestyle. In fact, increasing interests have been
      gathered around efficient strategies to use energy sources that do not generate
      high CO2 titers. Thus, science-funding agencies have invested more resources into
      research on hydrogen among other biofuels as interesting energy vectors. This
      article reviews present energy challenges and frames it into the present fuel
      usage landscape. Different strategies for hydrogen production are explained and
      evaluated. Focus is on biological hydrogen production; fermentation and photon
      fuelled hydrogen production are compared. Mathematical models in biology can be
      used to assess, explore and design production strategies for industrially
      relevant metabolites, such as biofuels. We assess the diverse construction and
      uses of genome-scale metabolic models of cyanobacterium Synechocystis sp. PCC6803
      to efficiently obtain biofuels. This organism has been studied as a potential
      photon-fuelled production platform for its ability to grow from carbon dioxide,
      water and photons, on simple culture media. Finally, we review studies that
      propose production strategies to weigh this organism's viability as a biofuel
      production platform. Overall, the work presented in this review unveils the
      industrial capabilities of cyanobacterium Synechocystis sp. PCC6803 to evolve
      interesting metabolites as a clean biofuel production platform. 

PMID- 24090243
TI  - Molecular details of ligand selectivity determinants in a promiscuous beta-glucan
      periplasmic binding protein.
AB  - BACKGROUND: Members of the periplasmic binding protein (PBP) superfamily utilize
      a highly conserved inter-domain ligand binding site that adapts to specifically
      bind a chemically diverse range of ligands. This paradigm of PBP ligand binding
      specificity was recently altered when the structure of the Thermotoga maritima
      cellobiose-binding protein (tmCBP) was solved. The tmCBP binding site is
      bipartite, comprising a canonical solvent-excluded region (subsite one), adjacent
      to a solvent-filled cavity (subsite two) where specific and semi-specific ligand
      recognition occur, respectively. RESULTS: A molecular level understanding of
      binding pocket adaptation mechanisms that simultaneously allow both ligand
      specificity at subsite one and promiscuity at subsite two has potentially
      important implications in ligand binding and drug design studies. We sought to
      investigate the determinants of ligand binding selectivity in tmCBP through
      biophysical characterization of tmCBP in the presence of varying beta-glucan
      oligosaccharides. Crystal structures show that whilst the amino acids that
      comprise both the tmCBP subsite one and subsite two binding sites remain fixed in
      conformation regardless of which ligands are present, the rich hydrogen bonding
      potential of water molecules may facilitate the ordering and the plasticity of
      this unique PBP binding site. CONCLUSIONS: The identification of the roles these
      water molecules play in ligand recognition suggests potential mechanisms that can
      be utilized to adapt a single ligand binding site to recognize multiple distinct
      ligands.

PMID- 24090245
TI  - Coenzyme Q10 production in plants: current status and future prospects.
AB  - Coenzyme Q10 (CoQ10) or Ubiquinone10 (UQ10), an isoprenylated benzoquinone, is
      well-known for its role as an electron carrier in aerobic respiration. It is a
      sole representative of lipid soluble antioxidant that is synthesized in our body.
      In recent years, it has been found to be associated with a range of patho
      physiological conditions and its oral administration has also reported to be of
      therapeutic value in a wide spectrum of chronic diseases. Additionally, as an
      antioxidant, it has been widely used as an ingredient in dietary supplements,
      neutraceuticals, and functional foods as well as in anti-aging creams. Since its
      limited dietary uptake and decrease in its endogenous synthesis in the body with
      age and under various diseases states warrants its adequate supply from an
      external source. To meet its growing demand for pharmaceutical, cosmetic and food
      industries, there is a great interest in the commercial production of CoQ10.
      Various synthetic and fermentation of microbial natural producers and their
      mutated strains have been developed for its commercial production. Although,
      microbial production is the major industrial source of CoQ10 but due to low yield
      and high production cost, other cost-effective and alternative sources need to be
      explored. Plants, being photosynthetic, producing high biomass and the
      engineering of pathways for producing CoQ10 directly in food crops will eliminate
      the additional step for purification and thus could be used as an ideal and cost
      effective alternative to chemical synthesis and microbial production of CoQ10. A
      better understanding of CoQ10 biosynthetic enzymes and their regulation in model
      systems like E. coli and yeast has led to the use of metabolic engineering to
      enhance CoQ10 production not only in microbes but also in plants. The plant-based
      CoQ10 production has emerged as a cost-effective and environment-friendly
      approach capable of supplying CoQ10 in ample amounts. The current strategies,
      progress and constraints of CoQ10 production in plants are discussed in this
      review. 

PMID- 24090248
TI  - Surface water quality is improving due to declining atmospheric N deposition.
AB  - We evaluated long-term surface water nitrate and atmospheric nitrogen (N)
      deposition trends for a group of nine predominantly forested Appalachian Mountain
      watersheds during a recent multidecadal period (1986-2009) in which regional NOx
      emissions have been progressively reduced. Statistical analysis showed unexpected
      linear declines in both annual surface water nitrate-N concentrations (mean
      =46.4%) and yields (mean =47.7%) among the watersheds corresponding to comparable
      declines in annual wet N deposition (mean =34.4%) resulting from U.S. NOx
      emission control programs during the same time period. Nitrate-N concentration
      trends were robust across a large geographical region and appeared insensitive to
      watershed size across several orders of magnitude-suggesting that the
      improvements in water quality are probably propagated to surface and estuarine
      waters downstream. Surface waters are thus responding to declining atmospheric N
      deposition in much the same way they responded to declining sulfur deposition
      although only one watershed showed a 1:1 relationship. Application of a kinetic N
      saturation model indicated that all nine forested watersheds are exhibiting signs
      of N saturation as evidenced by a limited, but variable, efficiency of demand for
      N. Further reductions in N deposition would be expected to produce additional
      reductions in streamwater N loads. 

PMID- 24090246
TI  - Diacylglycerol kinase delta promotes lipogenesis.
AB  - We have studied the relationship between diacylglycerol kinase delta (DGKdelta)
      and lipogenesis. There is a marked increase in the expression of DGKdelta during
      the differentiation of 3T3-L1 cells to adipocytes, as well as in the synthesis of
      neutral and polar lipids. When 3T3-L1 undifferentiated fibroblasts are
      transfected to express DGKdelta, there is increased triglyceride synthesis
      without differentiation to adipocytes. Hence, expression of DGKdelta promotes
      lipogenesis. Lipid synthesis is decreased in DGKdelta knockout mouse embryo
      fibroblasts, especially for lipids with shorter acyl chains and limited
      unsaturation. This reduction occurs for both neutral and polar lipids. These
      findings suggest reduced de novo lipid synthesis. This is confirmed by measuring
      the incorporation of glycerol into polar and neutral lipids, which is higher in
      the wild type cells than in the DGKdelta knockouts. In comparison, there was no
      change in lipid synthesis in DGKepsilon knockout mouse embryo fibroblasts. We
      also demonstrate that the DGKdelta knockout cells had a lower expression of
      acetyl-CoA carboxylase and fatty acid synthase as well as a lower degree of
      activation by phosphorylation of ATP citrate lyase. These three enzymes are
      involved in the synthesis of long chain fatty acids. Our results demonstrate that
      DGKdelta markedly increases lipid synthesis, at least in part as a result of
      promoting the de novo synthesis of fatty acids.

PMID- 24090247
TI  - No gender-related differences in the severity of nephropathia epidemica, Germany.
AB  - BACKGROUND: The number of cases of hantavirus disease caused by Puumala virus is
      increasing enormously in Germany within the last years. Men are overrepresented
      in hantavirus disease and differences in course and symptoms in relation to
      gender were reported from several countries. This study was conducted to define
      possible gender-specific risk factors and aspects of severity in hantavirus
      infections occurring in Germany. METHODS: Characteristics, clinical parameters
      and symptoms were recorded in a retrospective analysis of 108 patients with
      serologically confirmed hantavirus infection treated in our department. This
      cohort corresponds in regard to age, time of infection and gender ratio to the
      characteristics of the overall cases reported in Germany. RESULTS: The frequency
      of characteristic symptoms of hantavirus disease did not differ between males and
      females. The median of nadir and peak levels of clinical parameters did not
      exhibit relevant differences that would point to a more severe course in males or
      females. The clinical course and duration of hospitalization were similar for
      both sexes. No relevant differences in renal and pulmonary findings were
      observed. Males with hantavirus disease exhibited more cardiac findings than
      females.To compare the unequal gender distribution of the rodent-borne Puumala
      hantavirus disease with the gender ratio of other infectious diseases, we
      analyzed the gender ratio for notifiable infections according to their mode of
      transmission. Our data revealed a general overrepresentation of men in infections
      carried by arthropods and rodents. CONCLUSIONS: In contrast to reports from other
      countries, no crucial differences in the symptoms, course or severity of
      hantavirus disease between infected men and female were observed in our cohort.
      However behavioural differences may account for the fact that men are more often
      affected by certain infectious diseases than females.

PMID- 24090249
TI  - Independent control of adhesive and bulk properties of hybrid silica coatings on
      polycarbonate.
AB  - Transparent polymers are widely used in many applications ranging from automotive
      windows to microelectronics packaging. However, their intrinsic characteristics,
      in particular their mechanical properties, are significantly degraded with
      exposure to different weather conditions. For instance, under humid environment
      or UV-irradiation, polycarbonate (PC) undergoes depolymerization, leading to the
      release of Bisphenol A, a molecule presumed to be a hormonal disruptor,
      potentially causing health problems. This is a serious concern and the new REACH
      (Registration, Evaluation, Authorization and Restriction of Chemical substances )
      program dictates that materials releasing Bisphenol A should be removed from the
      market by January 1st, 2015 (2012-1442 law). Manufacturers have tried to satisfy
      this new regulation by depositing atop the PC a dense oxide-like protective
      coating that would act as a barrier layer. While high hardness, modulus, and
      density can be achieved by this approach, these coatings suffer from poor
      adhesion to the PC as evidenced by the numerous delamination events occurring
      under low scratch constraints. Here, we show that the combination of a N2/H2
      plasma treatment of PC before depositing a hybrid organic-inorganic solution
      leads to a coating displaying elevated hardness, modulus, and density, along with
      a very high adherence to PC (> 20 J/m(2) as measured by double cantilever beam
      test). In this study, the sol-gel coatings were composed of hybrid O/I silica
      (based on organoalkoxysilanes and colloidal silica) and designed to favor
      covalent bonding between the hybrid network and the surface treated PC, hence
      increasing the contribution of the plastic deformation from the substrate.
      Interestingly, double-cantilever beam (DCB) tests showed that the coating's
      adhesion to PC was the same irrespective of the organoalkoxysilanes/colloidal
      silica ratio. The versatility of the sol-gel deposition techniques (dip-coating,
      spray-coating, etc.), together with the excellent mechanical properties and
      exceptional adherence of this hybrid material to PC should lead to interesting
      new applications in diverse fields: optical eye-glasses, medical materials,
      packaging, and so forth. 

PMID- 24090250
TI  - Prognostic value of admission blood glucose level in patients with and without
      diabetes mellitus who sustain ST segment elevation myocardial infarction
      complicated by cardiogenic shock.
AB  - INTRODUCTION: Admission blood glucose (BG) level is a predictor of mortality in
      patients with ST-segment elevation myocardial infarction (STEMI). However,
      limited data are available relating admission BG to mortality in patients with
      STEMI complicated by cardiogenic shock, and it is not known whether diabetic
      status has an independent effect on this relationship. METHODS: Between November
      2005 and September 2010, 816 STEMI patients with cardiogenic shock were enrolled
      in a nationwide, prospective, multi-center registry; 239 (29.3%) had diabetes
      mellitus (DM). Patients were categorized according to BG levels at admission:
      <7.8, 7.8-10.9, 11.0-16.5 and >= 16.6 mmol/L. The primary outcome was 30-day
      mortality. The added values of BG to the Thrombolysis in Myocardial Infarction
      (TIMI) and Global Registry of Acute Coronary Events (GRACE) scores were assessed
      by receiver operating characteristic curves and integrated discrimination
      improvement analyses. RESULTS: Thirty-day mortality was higher in patients with
      higher admission BG (20.4%, 23.3%, 39.8%, and 43.1% p < 0.001). Among non
      diabetic patients, 30-day mortality was predicted by TIMI scores with a c
      statistic of 0.615 (95% confidence interval [CI], 0.561-0.662) and GRACE scores
      with a c-statistic of 0.652 (95% CI, 0.604-0.695). Incorporation of admission BG
      increased the c-statistic for TIMI score to 0.685 (95% CI, 0.639-0.720, p <
      0.001) and GRACE score to 0.708 (95% CI 0.664-0.742, p < 0.001). Additional
      predictive values for BG were not observed for diabetes. Integrated
      discrimination improvements (TIMI vs. additional BG and GRACE vs. additional BG)
      were 0.041 (p < 0.001) and 0.039 (p < 0.001) in non-diabetic patients.
      CONCLUSIONS: In a cohort of patients with STEMI complicated by cardiogenic shock,
      admission BG was an independent predictor of increased risk of mortality only
      among patients without DM.

PMID- 24090251
TI  - Ir-catalyzed preparation of SF5-substituted potassium aryl trifluoroborates via C
      H borylation and their application in the Suzuki-Miyaura reaction.
AB  - The preparation of new pentafluorosulfanyl-substituted potassium
      aryltrifluoroborates via Ir-catalyzed C-H borylation is reported. The utility of
      these novel building blocks was demonstrated in the Suzuki-Miyaura cross-coupling
      reaction, giving access to 3,5-disubstituted pentafluorosulfanylbenzenes. 

PMID- 24090252
TI  - Why are IPTp coverage targets so elusive in sub-Saharan Africa? A systematic
      review of health system barriers.
AB  - BACKGROUND: Use of intermittent preventive treatment (IPTp) is a proven cost
      effective intervention for preventing malaria in pregnancy. However, despite the
      roll-out of IPTp policies across Africa more than ten years ago, utilization
      levels remain low. This review sought to consolidate scattered evidence as to the
      health system barriers for IPTp coverage in the continent. METHODS AND FINDINGS:
      Relevant literature from Africa was systematically searched, reviewed and
      synthesized. Only studies containing primary data were considered. Studies reveal
      that: (i) poor leadership and governance contribute to slow decentralization of
      programme management, lack of harmonized guidelines, poor accountability
      mechanisms, such as robust monitoring and evaluation systems; (ii) low budgetary
      allocation towards policy implementation slows scale-up, while out-of-pocket
      expenditure deters women from seeking antenatal services that include IPTp; (iii)
      there are rampant human resource challenges including low staff motivation levels
      attributed to such factors as incorrect knowledge of IPTp recommendations and
      inadequate staffing; (iv) implementation of IPTp policies is hampered by
      prevailing service delivery barriers, such as long waiting time, long distances
      to health facilities and poor service provider/client relations; and (v) drug
      stock-outs and poor management of information and supply chains impair sustained
      availability of drugs for IPTp. CONCLUSIONS: For successful IPTp policy
      implementation, it is imperative that malaria control programmes target health
      system barriers that result in low coverage and hence programme ineffectiveness.

PMID- 24090253
TI  - Surgical treatment of Darier-Ferrand dermatofibrosarcoma: a systematic review.
AB  - BACKGROUND: Wide-excision surgery is required in Darier-Ferrand
      dermatofibrosarcoma protuberans, but there is no consensus regarding the lateral
      margins. MATERIALS AND METHODS: We performed a systematic review based on a
      MEDLINE search of articles, published from 1994 to 2009 to determine the optimal
      procedure to avoid recurrences and treatment morbidity. RESULTS: The analyzed
      articles included five meta-analyses of retrospective studies; three prospective,
      nonrandomized studies; and 35 retrospective studies. DISCUSSION: Positive deep
      margins may lead to a recurrence independent of lateral margin status. Despite an
      absence of formal evidence, wide excision with 3-cm margins appears to result in
      significantly less risk of a recurrence than surgery using <3-cm margins.
      Negative histologic margins appear to be the best criterion to decrease
      recurrence. Despite a lack of strong data, there was a marked tendency of Mohs
      micrographic surgery (MMS) to produce better results than conventional surgery.
      If MMS is unavailable, surgery using 3-cm lateral margins and a disease-free
      anatomic zone deep into the lesion is proposed. Slow Mohs could be a safe
      alternative to MMS when the latter technique is not available. Patients should be
      followed for a minimum of 10 years and preferably indefinitely.

PMID- 24090254
TI  - Botulinum toxin in men: review of relevant anatomy and clinical trial data.
AB  - BACKGROUND: Botulinum toxin is widely used for facial aesthetics, and its use in
      men continues to increase. OBJECTIVE: To provide a review of pertinent male
      anatomic features and updated clinical information on the use of botulinum toxin
      in men. METHODS: A Medline search was performed for publications on sex
      differences in facial anatomy and on clinical studies examining the role of sex
      in botulinum toxin treatment. RESULTS: There are substantial facial anatomic
      differences between the sexes, with men having increased cranial size, unique
      cranial shape, greater skeletal muscle mass, higher density of facial blood
      vessels, and more-severe facial rhytides. A review of sex and botulinum toxin
      treatment identified 17 clinical studies with 5,646 total participants, of whom
      629 (11.1%) were male. Only two studies accounted for sex in study design or
      subgroup analysis. Both studies found abobotulinumtoxinA to be less effective in
      men. An additional study examining onabotulinumtoxinA dosing in men found that
      higher doses than typically used in women were more efficacious. There were not
      more adverse events in male participants in any study. CONCLUSION: Despite sex
      differences in facial anatomy, the use of botulinum toxin in men is inadequately
      studied with regard to dosing, efficacy, and safety.

PMID- 24090255
TI  - Gentlemen, relax: commentary on botulinum toxin in men: a review of relevant
      anatomy and clinical trial data.

PMID- 24090256
TI  - Quantitative volumetric analysis of progressive hemifacial atrophy corrected
      using stromal vascular fraction-supplemented autologous fat grafts.
AB  - BACKGROUND: Progressive hemifacial atrophy (Parry-Romberg disease) is rare and
      involves all skin layers and subcutaneous soft and hard tissue. Autologous fat
      grafting has revolutionized the field of soft-tissue reconstruction and
      augmentation, but long-term maintenance is unpredictable. Stromal vascular
      fraction (SVF)-supplemented cell therapy offers new hope for improving fat graft
      survival, with good long-term results, but efficacy and long-term outcome in the
      clinic are rarely studied using objective data. OBJECTIVE: To compare the long
      term viability of SVF-supplemented fat grafts and fat grafts alone for contour
      reconstruction of progressive hemifacial atrophy using quantitative volume
      analysis. METHODS: We treated 20 patients with stable hemifacial atrophy for at
      least 2 years with SVF-supplemented autologous fat grafting (n = 10) or fat
      grafting alone (n = 10). All patients were followed up every 3 months. Hemifacial
      volume was measured using computed tomography and the Philips Extended Brilliance
      Workspace. RESULTS: All patients had successful outcomes without complications,
      but fat survival and clinical improvement was greater with SVF-supplemented
      grafting than fat grafting alone after 6 months. CONCLUSION: SVF-supplemented
      autologous fat transplantation is effective and safe for treating progressive
      hemifacial atrophy and can enhance the survival of grafts in the face without
      major complications.

PMID- 24090257
TI  - Delayed-onset complications of facial soft tissue augmentation with permanent
      fillers in 85 patients.
AB  - OBJECTIVE: To evaluate factors influencing the onset and type of adverse events
      in patients injected with permanent fillers in the face and to propose a
      therapeutic strategy for these complications. METHODS: A prospectively attained
      series of 85 patients with delayed-onset complications after facial injection
      with permanent fillers underwent clinical follow-up and treatment of the
      complications. RESULTS: Lag times until onset and type of delayed-onset
      complication varied according to filler material. In 28% (n = 24) of the cases,
      patients reported the onset of complications after dental procedures, additional
      injections with fillers, or other invasive treatments in the facial area. Forty
      eight (57%) patients required invasive treatment. Abscess formation was
      significantly more frequent in patients with human immunodeficiency virus
      infection and facial lipoatrophy (p = .001). CONCLUSION: The intrinsic
      characteristics of the injected filler and the immune status of the patient play
      important roles in the diversity of time of onset and type of delayed-onset
      adverse events observed. It seems that invasive facial or oral procedures in the
      vicinity of filler depots can provoke such complications. We propose a strategy
      for treating these complications and advise great caution when using permanent
      filling agents.

PMID- 24090258
TI  - Oral antibiotics versus topical decolonization to prevent surgical site infection
      after Mohs micrographic surgery--a randomized, controlled trial.
AB  - BACKGROUND: The optimal method of reducing the risk of surgical site infection
      (SSI) after dermatologic surgery is unclear. Empiric, preoperative antibiotic use
      is common practice but lacks supporting evidence for its efficacy in preventing
      SSI. Risk stratification for patients at high risk of postoperative SSI based on
      a nasal swab is a viable strategy when coupled with topical decolonization for
      positive carriers. We compared the rates of infection in patients undergoing Mohs
      micrographic surgery (MMS) with nasal carriage of Staphylococcus aureus who
      received oral antibiotics or topical decolonization. METHODS: A randomized,
      controlled trial with 693 patients was conducted over a 30-week period at a
      single surgical practice. Patients were stratified into nasal carriers or
      noncarriers of S. aureus based on a preoperative nasal swab. Nasal carriers of S.
      aureus were randomized to receive topical decolonization with intranasal
      mupirocin twice daily plus 4% chlorhexidine gluconate body wash daily for 5
      consecutive days before surgery or statim pre- and postoperative doses of oral
      cephalexin. RESULTS: One hundred seventy-nine patients (25.8%) were identified as
      carriers of S. aureus. Ninety received topical decolonization, and 89 received
      oral antibiotics. These groups were compared with a swab-negative Mohs surgical
      cohort over the same time period. There were no significant differences between
      the groups in terms of demographic characteristics or comorbidities. Nine percent
      of patients receiving oral antibiotic prophylaxis and 0% receiving topical
      decolonization developed early SSI (p = .003). CONCLUSION: In patients with
      demonstrable carriage of S. aureus, topical decolonization resulted in fewer SSI
      than in patients receiving perioperative oral antibiotics. Antibiotics should be
      reserved for clinically suspected and swab-proven infections rather than being
      prescribed empirically. Further efforts should be directed toward optimizing
      endogenous risk factor control for all patients presenting for MMS.

PMID- 24090259
TI  - A preoperative approach to postoperative infections?

PMID- 24090260
TI  - Patient perceptions of nonmelanoma skin cancer before diagnosis.
AB  - BACKGROUND: There is a paucity of data regarding patient perceptions of
      nonmelanoma skin cancer (NMSC). OBJECTIVE: To describe patients' perceptions of
      skin lesions before a diagnosis of NMSC. METHODS: This was a descriptive study in
      a private practice setting. Patients with a previous biopsy of NMSC who presented
      for treatment were eligible. A self-administered questionnaire assessed what
      patient perceptions of lesions diagnosed as NMSCs had been before they were aware
      of the diagnosis. Medical records were reviewed for tumor type, size, and
      location. RESULTS: One hundred sixty-three consecutive patients undergoing
      treatment for NMSC completed the questionnaire. The most common initial
      impressions of the lesion were skin cancer (20%), acne (19%), sore (10%), unknown
      (9%), dry skin (7%), age spot (6%), and injury (6%). Seventy-two percent of
      patients were the first to notice the lesion. Patients with a history of skin
      cancer were more likely to think the lesion was a skin cancer on initial
      impression (28% vs. 8%) (p < .001). CONCLUSIONS: Understanding how patients
      perceive their skin cancers may aid in targeting educational strategies and
      increase awareness of skin cancer risk. Our data suggest that there are important
      subtleties in self-identification that may need to be taken into consideration in
      any educational campaign targeting NMSC.

PMID- 24090261
TI  - Gene expression profiling for cardiac rejection surveillance is not predictive of
      post-transplantation skin cancer.
AB  - BACKGROUND: The risk of skin cancer in solid organ transplant recipients (SOTR)
      is 50 to 100 times as great as in those without a transplant. Multiple factors,
      including immunosuppression, influence the development of post-transplantation
      skin cancer. Individuals with cardiac transplant are serially screened for organ
      rejection and immunosuppressive regimen effectiveness. Gene expression profiling
      of peripheral blood mononuclear cells has been established as a noninvasive test
      for monitoring cardiac rejection. OBJECTIVE: We examined individuals with cardiac
      transplant monitored using peripheral gene expression profiling to determine
      whether the profile of peripheral blood mononuclear cell activity could correlate
      with the development of post-transplantation skin cancer. METHODS AND MATERIALS:
      Sixty-one patient records were examined for initial endomyocardial biopsy
      results, gene expression profiling data, immunosuppressive regimens, and post
      transplantation skin cancer. RESULTS: There was no relationship between acute
      rejection and the development of skin cancer. No relationship between peripheral
      gene expression profiling and the development of post-transplantation skin cancer
      was observed. The most common skin cancer in the population was squamous cell
      carcinoma. SOTR suppressed with azathioprine had a significantly higher incidence
      of squamous cell carcinoma. CONCLUSION: Although gene expression tests have
      advanced transplant surveillance, they were not associated with post
      transplantation skin cancer.

PMID- 24090262
TI  - Quick and easy correction of a symptomatic pincer nail using a shape memory alloy
      device.
AB  - BACKGROUND: Pincer nails are characterized by the transverse curvature increasing
      from the proximal to the distal aspect along the longitudinal axis. A novel
      treatment technique using a shape memory alloy device was recently introduced.
      OBJECTIVE: To determine the treatment outcomes and safety of a shape memory alloy
      device. METHODS AND MATERIALS: This was a retrospective analysis of 21 cases of
      pincer nail of the great toe in 14 patients. Subjective indices (pain,
      inconvenience, global assessment scores) and objective parameters (transverse
      angle, width index) on days 0 (D0) and 1 (D1) and weeks 2 (W2) and 12 (W12) were
      investigated. RESULTS: All parameters started to show significant improvement on
      D1. From D0 to D1, pain score fell from 3.6 +/- 1.0 to 1.5 +/- 0.7, inconvenience
      score fell from 3.3 +/- 1.0 to 1.5 +/- 0.7, global assessment score increased
      from 1.5 +/- 0.7 to 2.5 +/- 0.7, transverse angle improved from 86.4 +/- 27.7
      degrees  to 114.7 +/- 21.6 degrees , and width index improved from 67.6 +/- 13.1%
      to 89.0 +/- 9.7%. These effects were consistent during 12 weeks of follow-up. Two
      cases (9.5%) recurred, but symptoms were less severe than before. No complication
      was identified. CONCLUSION: A shape memory alloy device was an effective and safe
      way to rapidly correct symptomatic pincer nail deformity.

PMID- 24090263
TI  - Tie-over bolster for second-intention wound healing.

PMID- 24090264
TI  - Targeting leukotriene B4 in inflammation.
AB  - INTRODUCTION: Leukotriene (LT) B(4) is a powerful proinflammatory lipid mediator
      and triggers adherence to the endothelium, activates and recruits leukocytes to
      the site of injury. When formed in excess, LTB(4) plays a pathogenic role and may
      sustain chronic inflammation in diseases such as asthma, rheumatoid arthritis,
      and inflammatory bowel disease. Recent investigations have also indicated that
      LTB(4) is involved in cardiovascular diseases. AREAS COVERED: As the 5
      lipoxygenase pathway involves several discrete, tightly coupled, enzymes, which
      convert the substrate, 'step by step', into bioactive products, several different
      strategies have been used to target LTB(4) as a means to treat inflammation.
      Here, we discuss recent findings regarding the development of selective enzyme
      inhibitors and antagonists for LTB(4) receptors, as well as their application in
      preclinical and clinical studies. EXPERT OPINION: Components of the 5
      lipoxygenase pathway have received considerable attention as candidate drug
      targets resulting in one new class of medications against asthma, that is, the
      antileukotrienes. However, efforts to specifically target LTB(4) have not yet
      been fruitful in the clinical setting, in spite of very promising preclinical
      data. Recently, crystal structures along with hitherto unknown functions of key
      enzymes in the leukotriene cascade have emerged, offering new opportunities for
      drug development and, with time, pharmacological intervention in LTB(4)-mediated
      pathologies.

PMID- 24090265
TI  - Unsupervised segmentation of noisy electron microscopy images using salient
      watersheds and region merging.
AB  - BACKGROUND: Segmenting electron microscopy (EM) images of cellular and
      subcellular processes in the nervous system is a key step in many bioimaging
      pipelines involving classification and labeling of ultrastructures. However,
      fully automated techniques to segment images are often susceptible to noise and
      heterogeneity in EM images (e.g. different histological preparations, different
      organisms, different brain regions, etc.). Supervised techniques to address this
      problem are often helpful but require large sets of training data, which are
      often difficult to obtain in practice, especially across many conditions.
      RESULTS: We propose a new, principled unsupervised algorithm to segment EM images
      using a two-step approach: edge detection via salient watersheds following by
      robust region merging. We performed experiments to gather EM neuroimages of two
      organisms (mouse and fruit fly) using different histological preparations and
      generated manually curated ground-truth segmentations. We compared our algorithm
      against several state-of-the-art unsupervised segmentation algorithms and found
      superior performance using two standard measures of under-and over-segmentation
      error. CONCLUSIONS: Our algorithm is general and may be applicable to other large
      scale segmentation problems for bioimages.

PMID- 24090266
TI  - Randomized controlled trial of pharmacological replacement of melatonin for sleep
      disruption in individuals with tetraplegia.
AB  - OBJECTIVE: To determine the effectiveness of a melatonin agonist for treating
      sleep disturbances in individuals with tetraplegia. DESIGN: Placebo-controlled,
      double-blind, crossover, randomized control trial. SETTING: At home.
      PARTICIPANTS: Eight individuals with tetraplegia, having an absence of endogenous
      melatonin production and the presence of a sleep disorder. Interventions Three
      weeks of 8 mg of ramelteon (melatonin agonist) and 3 weeks of placebo (crossover,
      randomized order) with 2 weeks of baseline prior to and 2 weeks of washout
      between active conditions. OUTCOME: Change in objective and subjective sleep.
      MEASURES: Wrist actigraphy, post-sleep questionnaire, Stanford sleepiness scale,
      SF-36. RESULTS: We observed no consistent changes in either subjective or
      objective measures of sleep, including subjective sleep latency (P = 0.55,
      Friedman test), number of awakenings (P = 0.17, Friedman test), subjective total
      sleep time (P = 0.45, Friedman test), subjective morning alertness (P = 0.35,
      Friedman test), objective wake after sleep onset (P = 0.70, Friedman test), or
      objective sleep efficiency (P = 0.78, Friedman test). There were significant
      increases in both objective total sleep time (P < 0.05, Friedman test),
      subjective time in bed (P < 0.05, Friedman test), and subjective sleep quality (P
      < 0.05, Friedman test), although these occurred in both arms. There were no
      significant changes in any of the nine SF-36 subscale scores (Friedman test, Ps
      >Bonferroni adjusted alpha of 0.005). CONCLUSION: In this pilot study, we were
      unable to show effectiveness of pharmacological replacement of melatonin for the
      treatment of self-reported sleep problems in individuals with tetraplegia. Trial
      Registration ClinicalTrials.gov # NCT00507546.

PMID- 24090267
TI  - Lumbar vertebral hemangioma mimicking lateral spinal canal stenosis: case report
      and review of literature.
AB  - Context Hemangiomas are the commonest benign tumors of the spine. Most occur in
      the thoracolumbar spine and the majority are asymptomatic. Rarely, hemangiomas
      cause symptoms through epidural expansion of the involved vertebra, resulting in
      spinal canal stenosis, spontaneous epidural hemorrhage, and pathological burst
      fracture. Findings We report a rare case of a 73-year-old woman, who had been
      treated for two months for degenerative neurogenic claudication. On admission,
      magnetic resonance imaging and computed tomographic scans revealed a hemangioma
      of the third lumbar vertebra protruding to the epidural space producing lateral
      spinal stenosis and ipsilateral nerve root compression. The patient underwent
      successful right hemilaminectomy for decompression of the nerve root, balloon
      kyphoplasty with poly-methyl methacrylate (PMMA) and pedicle screw segmental
      stabilization. Postoperative course was uneventful. Conclusion In the elderly,
      this rare presentation of spinal stenosis due to hemangiomas may be encountered.
      Decompression and vertebral augmentation by means balloon kyphoplasty with PMMA
      plus segmental pedicle screw fixation is recommended. 

PMID- 24090268
TI  - Sub-100-nm ordered silicon hole arrays by metal-assisted chemical etching.
AB  - Sub-100-nm silicon nanohole arrays were fabricated by a combination of the site
      selective electroless deposition of noble metals through anodic porous alumina
      and the subsequent metal-assisted chemical etching. Under optimum conditions, the
      formation of deep straight holes with an ordered periodicity (e.g., 100 nm
      interval, 40 nm diameter, and high aspect ratio of 50) was successfully achieved.
      By using the present method, the fabrication of silicon nanohole arrays with 60
      nm periodicity was also achieved. 

PMID- 24090269
TI  - Periodic deformation of microsize droplets in a microchannel induced by a
      transverse alternating electric field.
AB  - When a water droplet is suspended in an immiscible, insulating liquid medium of
      essentially infinite dimensions and is subjected to a periodically alternating
      electric field, it will undergo periodic deformation at a frequency twice that of
      the field. This work examined the periodic deformation and bursting of microsize
      water droplets in silicone oil moving through a PTFE microchannel with an inner
      diameter nearly twice that of the droplets, under a periodically alternating
      electric field normal to the direction of flow. When the sinusoidal electric
      field was either relatively weak or had a low frequency, the droplets displayed
      periodic deformation alternating between a prolate ellipsoidal along the electric
      field direction and a sphere. In contrast, droplets alternated between prolate
      and oblate shapes when the electric field strength was high or the frequency of
      the electric field was high. When the applied electric field strength was
      increased, a constriction formed in the central portion of droplets which had
      deformed into a prolate ellipsoid. When the electric field strength was further
      increased, droplets broke into two or more smaller droplets as the result of the
      inertial force acting on the water in the droplet and the electrostatic force at
      the interface of the droplet and the surrounding liquid. The majority of the
      small droplets formed by such breakups subsequently merged into single droplets
      over the course of time. 

PMID- 24090270
TI  - Polymorphic variants of SLCO1B1 in neonatal hyperbilirubinemia in China.
AB  - BACKGROUND: To evaluate the association between the genetic polymorphism of the
      solute carrier organic anion transporter family member 1B1 (SLCO1B1, also known
      as organic anion transport polypeptide C) and hyperbilirubinemia in Chinese
      neonates. METHODS: 183 infants with hyperbilirubinemia and 192 control subjects
      from the Fifth People's Hospital of Shenzhen were recruited. Polymerase chain
      reaction, restriction fragment length polymorphisms and agarose gel
      electrophoresis techniques were used to detect genetic variants of SLCO1B1.
      RESULTS: The study revealed that SLCO1B1 388 G > A occurred significantly more
      frequently in neonates with hyperbilirubinemia than in controls (RR = 1.50; 95%
      CI: 1.13-2.00). There were no significant differences in SLCO1B1 521 T > C
      between the hyperbilirubinemia and the control group (RR, 1.00; 95% CI, 0.72
      1.40). No carriage of the C to A substitution at nucleotide 463 was detected.
      CONCLUSION: The SLCO1B1 388 G > A variant is associated with neonatal
      hyperbilirubinemia in Chinese neonates.

PMID- 24090271
TI  - Snapshot of a DNA polymerase while incorporating two consecutive C5-modified
      nucleotides.
AB  - Functional nucleotides are important in many cutting-edge biomolecular
      techniques. Often several modified nucleotides have to be incorporated
      consecutively. This structural study of KlenTaq DNA polymerase, a truncated form
      of Thermus aquaticus DNA polymerase, gives first insights how multiple
      modifications are processed by a DNA polymerase and, therefore, contribute to the
      understanding of these enzymes in their interplay with artificial substrates. 

PMID- 24090274
TI  - Diverse synthesis of marine cyclic depsipeptide lagunamide A and its analogues.
AB  - The asymmetric total synthesis of lagunamide A (3.0%, 20 steps longest linear
      sequence) and its five analogues, including the structure dehydrated at the C37
      position, are detailed in this report. The key feature in this diverse synthesis
      includes the elaboration of four consecutive chiral centers at C37-40 and the
      final macrocyclization. Starting from chiral aldehyde 10, we synthesized both 1,3
      anti and 1,3-syn homoallylic alcohols 20a and 20b through asymmetric aldol
      condensation and stereoselective allylation. The following esterification to
      introduce the L-N-Me-Ala unit resulted in significant epimerization. This problem
      was finally overcome by coupling the alcohols with the corresponding acid
      chloride of the L-alanine derivative. The key alpha,beta-unsaturated carboxylic
      acid unit was produced by cross-metathesis (CM) of methacrylaldehyde and related
      olefins. Interestingly, we found that the C7 configuration dramatically affected
      the ring closure. Natural lagunamide A (1a), its 39-epimer (1c), and its 2-epimer
      (1d) were obtained through macrolactamization between alanine and isoleucine
      moieties.

PMID- 24090275
TI  - Nanocoax-based electrochemical sensor.
AB  - We have used a facile polymer imprint process to fabricate a three-dimensional
      electrochemical nanosensor, the sensitivity of which is two decades higher than
      that of planar controls. The device is composed of an array of vertically
      oriented nanoscale coaxial electrodes, with the coax cores and shields serving as
      integrated working and counter electrodes, respectively, each with a nanoscale
      separation gap (coax annulus width). Arrays of ~10(6) devices per square
      millimeter were prepared with different gaps, with smaller gaps yielding higher
      sensitivity. A coax-based sensor with a 100 nm gap was found to have sensitivity
      90 times greater than that of a planar sensor control, which had conventional
      millimeter-scale electrode gap spacing. We suggest that this enhancement is due
      to the combination of rapid diffusion of molecules between the closely spaced
      electrodes and the large number of nanoscale electrochemical cells operating in
      parallel, both of which enhance current per unit surface area compared to planar
      or other nanostructured devices.

PMID- 24090277
TI  - Synthesis and characterization of MnCrO4, a new mixed-valence antiferromagnet.
AB  - A new orthorhombic phase, MnCrO4, isostructural with MCrO4 (M = Mg, Co, Ni, Cu,
      Cd) was prepared by evaporation of an aqueous solution, (NH4)2Cr2O7 + 2 Mn(NO3)2,
      followed by calcination at 400  degrees C. It is characterized by redox
      titration, Rietveld analysis of the X-ray diffraction pattern, Cr K edge and Mn K
      edge XANES, ESR, magnetic susceptibility, specific heat and resistivity
      measurements. In contrast to the high-pressure MnCrO4 phase where both cations
      are octahedral, the new phase contains Cr in a tetrahedral environment suggesting
      the charge balance Mn(2+)Cr(6+)O4. However, the positions of both X-ray
      absorption K edges, the bond lengths and the ESR data suggest the occurrence of
      some mixed-valence character in which the mean oxidation state of Mn is higher
      than 2 and that of Cr is lower than 6. Both the magnetic susceptibility and the
      specific heat data indicate an onset of a three-dimensional antiferromagnetic
      order at TN ~ 42 K, which was confirmed also by calculating the spin exchange
      interactions on the basis of first principles density functional calculations.
      Dynamic magnetic studies (ESR) corroborate this scenario and indicate appreciable
      short-range correlations at temperatures far above TN. MnCrO4 is a semiconductor
      with activation energy of 0.27 eV; it loses oxygen on heating above 400  degrees
      C to form first Cr2O3 plus Mn3O4 and then Mn1.5Cr1.5O4 spinel. 

PMID- 24090278
TI  - Mesoporous carbon-carbon nanotube-sulfur composite microspheres for high-areal
      capacity lithium-sulfur battery cathodes.
AB  - Lithium-sulfur (Li-S) batteries offer theoretical energy density much higher than
      that of lithium-ion batteries, but their development faces significant
      challenges. Mesoporous carbon-sulfur composite microspheres are successfully
      synthesized by combining emulsion polymerization and the evaporation-induced self
      assembly (EISA) process. Such materials not only exhibit high sulfur-specific
      capacity and excellent retention as Li-S cathodes but also afford much improved
      tap density, sulfur content, and areal capacity necessary for practical
      development of high-energy-density Li-S batteries. In addition, when incorporated
      with carbon nanotubes (CNTs) to form mesoporous carbon-CNT-sulfur composite
      microspheres, the material demonstrated superb battery performance even at a high
      current density of 2.8 mA/cm(2), with a reversible capacity over 700 mAh/g after
      200 cycles. 

PMID- 24090276
TI  - Depurination of N7-methylguanine by DNA glycosylase AlkD is dependent on the DNA
      backbone.
AB  - DNA glycosylase AlkD excises N7-methylguanine (7mG) by a unique but unknown
      mechanism, in which the damaged nucleotide is positioned away from the protein
      and the phosphate backbone is distorted. Here, we show by methylphosphonate
      substitution that a phosphate proximal to the lesion has a significant effect on
      the rate enhancement of 7mG depurination by the enzyme. Thus, instead of a
      conventional mechanism whereby protein side chains participate in N-glycosidic
      bond cleavage, AlkD remodels the DNA into an active site composed exclusively of
      DNA functional groups that provide the necessary chemistry to catalyze
      depurination. 

PMID- 24090279
TI  - The long-term coronary heart disease risk of previously obese patients with type
      2 diabetes mellitus.
AB  - BACKGROUND: Obesity is associated with insulin resistance, development of
      diabetes, and coronary heart disease. There is limited information on the
      contribution of previous obesity on the risk of coronary heart disease. We aimed
      to examine the effect of previous history of obesity on the occurrence of
      coronary heart disease in patients with diabetes. METHODS: We carried out a
      retrospective chart analysis of 315 type 2 diabetic patients without obesity and
      without atherosclerotic cardiovascular events at their initial hospital visit
      (men/women 236/79; mean +/- standard deviation; age 53.1 +/- 6.6 years; maximal
      body mass index before enrollment (MAXBMI) 26.6 +/- 3.4 kg/m2; decrease of the
      BMI at enrollment from MAXBMI (deltaBMI) 4.23 +/- 2.62 kg/m2) to investigate the
      association of previous obesity (MAXBMI larger than 30 kg/m2) with the long-term
      incidence of cardiovascular events. Of 315 patients, forty-eight were previously
      obese. RESULTS: After median follow-up of 13.9 years, 48 patients developed
      coronary heart disease. The Kaplan-Meier analysis exhibited that coronary heart
      disease occurred more frequently in previously obese patients than in subjects in
      the reference category (22 kg/m2 < or = MAXBMI < 25 kg/m2) and that the effect
      lasted proportionally over follow-up periods. Multivariate Cox regression models
      showed that hazard ratios and corresponding 95% confidence intervals of coronary
      heart disease for patients with previous obesity compared with subjects in the
      reference category were 2.52 and 1.15 to 5.50 (p value = 0.020) after adjustment
      for age, sex, smoking status, systolic blood pressure, total cholesterol and HDL
      cholesterol. In this cohort, deltaBMI strongly correlated with MAXBMI and also
      behaved as a risk factor. The hazard ratios and 95% confidence intervals by the
      increment of one standard deviation of deltaBMI after adjustment for age, sex,
      smoking status, systolic blood pressure, total cholesterol and HDL cholesterol
      were 1.38 and 1.08 to 1.79 (p value = 0.013). CONCLUSIONS: Previous obesity
      and/or large body weight loss before admission might act as an increased risk for
      coronary heart disease.

PMID- 24090280
TI  - Long-term survival after intensive care unit discharge in Thailand: a
      retrospective study.
AB  - INTRODUCTION: Economic evaluations of interventions in the hospital setting often
      rely on the estimated long-term impact on patient survival. Estimates of
      mortality rates and long-term outcomes among patients discharged alive from the
      intensive care unit (ICU) are lacking from lower- and middle-income countries.
      This study aimed to assess the long-term survival and life expectancy (LE)
      amongst post-ICU patients in Thailand, a middle-income country. METHODS: In this
      retrospective cohort study, data from a regional tertiary hospital in northeast
      Thailand and the regional death registry were linked and used to assess patient
      survival time after ICU discharge. Adult ICU patients aged at least 15 years who
      had been discharged alive from an ICU between 1 January 2004 and 31 December 2005
      were included in the study, and the death registry was used to determine deaths
      occurring in this cohort up to 31st December 2010. These data were used in
      conjunction with standard mortality life tables to estimate annual mortality and
      life expectancy. RESULTS: This analysis included 10,321 ICU patients. During ICU
      admission, 3,251 patients (31.5%) died. Of 7,070 patients discharged alive, 2,527
      (35.7%) were known to have died within the five-year follow-up period, a
      mortality rate 2.5 times higher than that in the Thai general population (age and
      sex matched). The mean LE was estimated as 18.3 years compared with 25.2 years in
      the general population. CONCLUSIONS: Post-ICU patients experienced much higher
      rates of mortality than members of the general population over the five-year
      follow-up period, particularly in the first year after discharge. Further work
      assessing Health Related Quality of Life (HRQOL) in both post-ICU patients and in
      the general population in developing countries is needed.

PMID- 24090281
TI  - Chirality transfer in 1D self-assemblies: influence of H-bonding vs metal
      coordination between dicyano[7]helicene enantiomers.
AB  - Chiral recognition as well as chirality transfer in supramolecular self-assembly
      and on-surface coordination is studied for the enantiopure 6,13
      dicyano[7]helicene building block. It is remarkable that, with this helical
      molecule, both H-bonded chains and metal-coordinated chains can be formed on the
      same substrate, thereby allowing for a direct comparison of the chain bonding
      motifs and their effects on the self-assembly in experiment and theory.
      Conformational flexure and both adsorbate/adsorbent and intermolecular
      interactions can be identified as factors influencing the chiral recognition at
      the binding site. The observed H-bonded chains are chiral, however, the overall
      appearance of Cu-coordinated chains is no longer chiral. The study was performed
      via scanning tunneling microscopy, X-ray-photoelectron spectroscopy and density
      functional theory calculations. We show a significant influence of the molecular
      flexibility and the type of bonding motif on the chirality transfer in the 1D
      self-assembly. 

PMID- 24090282
TI  - A comparison of three tocolytics for preterm labor: a randomized clinical trial.
AB  - OBJECTIVE: To compare the efficacy and maternal side effects of nifedipine (N),
      magnesium sulfate (M), and indomethacin (I) for acute tocolysis. METHODS: In this
      single center randomized trial, women in preterm labor 24-32 weeks' gestation
      received intravenous M, oral N, or I suppositories. The primary outcomes of
      interest were arrest of preterm labor (>48 h, >=7 days), gestational age at
      delivery, and maternal side effects. RESULTS: Over a 38-month period, 301 women
      were allocated to receive M (90), N (114), or I (90). Gestational age at delivery
      (p = 0.551) or arrest of labor >48 h, >7 days were similar between the three
      groups (p = 0.199, 0.654). Hypotension and tachycardia were more common in N
      patients compared to women receiving M or I (p = 0.003, 0.009). Patients
      receiving I had more fetal ductal constriction or oligohydramnios compared to M
      or N (p = 0.001, 0.020) but, I women were tested more often. There was one case
      of pulmonary edema in the M group and one with plural effusion in the N group.
      CONCLUSION: There were no differences in efficacy or in major maternal safety
      issues between the three tocolytic agents. Since there is no FDA approved
      tocolytic to treat preterm labor, clinicians should use the tocolytic that has
      afforded them the best results with the least maternal/neonatal side effects.

PMID- 24090283
TI  - Evaluation of the effectiveness of simple nuclei-segmentation methods on
      Caenorhabditis elegans embryogenesis images.
AB  - BACKGROUND: For the analysis of spatio-temporal dynamics, various automated
      processing methods have been developed for nuclei segmentation. These methods
      tend to be complex for segmentation of images with crowded nuclei, preventing the
      simple reapplication of the methods to other problems. Thus, it is useful to
      evaluate the ability of simple methods to segment images with various degrees of
      crowded nuclei. RESULTS: Here, we selected six simple methods from various
      watershed based and local maxima detection based methods that are frequently used
      for nuclei segmentation, and evaluated their segmentation accuracy for each
      developmental stage of the Caenorhabditis elegans. We included a 4D noise filter,
      in addition to 2D and 3D noise filters, as a pre-processing step to evaluate the
      potential of simple methods as widely as possible. By applying the methods to
      image data between the 50- to 500-cell developmental stages at 50-cell intervals,
      the error rate for nuclei detection could be reduced to <= 2.1% at every stage
      until the 350-cell stage. The fractions of total errors throughout the stages
      could be reduced to <= 2.4%. The error rates improved at most of the stages and
      the total errors improved when a 4D noise filter was used. The methods with the
      least errors were two watershed-based methods with 4D noise filters. For all the
      other methods, the error rate and the fraction of errors could be reduced to <=
      4.2% and <= 4.1%, respectively. The minimum error rate for each stage between the
      400- to 500-cell stages ranged from 6.0% to 8.4%. However, similarities between
      the computational and manual segmentations measured by volume overlap and
      Hausdorff distance were not good. The methods were also applied to Drosophila and
      zebrafish embryos and found to be effective. CONCLUSIONS: The simple segmentation
      methods were found to be useful for detecting nuclei until the 350-cell stage,
      but not very useful after the 400-cell stage. The incorporation of a 4D noise
      filter to the simple methods could improve their performances. Error types and
      the temporal biases of errors were dependent on the methods used. Combining
      multiple simple methods could also give good segmentations.

PMID- 24090284
TI  - Leisure repertoire among persons with a spinal cord injury: interests,
      performance, and well-being.
AB  - OBJECTIVE: To explore and describe the leisure repertoire of persons with
      traumatic spinal cord injury (SCI) and how the repertoire is related to interest,
      performance, and well-being. DESIGN: Cross-sectional study. SETTING: A total of
      97 persons with traumatic SCI were recruited from the non-profit national
      organization, RG Active Rehabilitation in Sweden. OUTCOME MEASURE: Data were
      collected through a two-part postal survey. The first comprised of questions
      investigating socio-demographic variables and injury characteristics; the second
      part included an interest checklist with 20 areas of leisure activities. RESULTS:
      The participants were mostly interested in, performed, and experienced well-being
      from social and culture activities and TV/DVD/movies. The areas of leisure
      activities in which they had most likely experienced changes after the SCI were
      outdoor activities, exercise, and gardening. Sex, age, and to some extent, time
      since injury were related to interest, performance, well-being, and changed
      performance. CONCLUSIONS: The results provided an explanation and limited
      description of a changed leisure repertoire among persons after a traumatic SCI.
      The study showed that sex, age, and time since injury were more closely related
      to the choice of leisure activities to include in the leisure repertoire than the
      level of injury. This knowledge can be of importance when professionals in the
      field of rehabilitation are planning and implementing interventions concerning
      leisure activities for persons with SCI.

PMID- 24090286
TI  - Distribution of selected healthcare resources for influenza pandemic response in
      Cambodia.
AB  - INTRODUCTION: Human influenza infection poses a serious public health threat in
      Cambodia, a country at risk for the emergence and spread of novel influenza
      viruses with pandemic potential. Prior pandemics demonstrated the adverse impact
      of influenza on poor communities in developing countries. Investigation of
      healthcare resource distribution can inform decisions regarding resource
      mobilization and investment for pandemic mitigation. METHODS: A health facility
      survey performed across Cambodia obtained data on availability of healthcare
      resources important for pandemic influenza response. Focusing on five key
      resources considered most necessary for treating severe influenza (inpatient
      beds, doctors, nurses, oseltamivir, and ventilators), resource distributions were
      analyzed at the Operational District (OD) and Province levels, refining data
      analysis from earlier studies. Resources were stratified by respondent type
      (hospital vs. District Health Office [DHO]). A summary index of distribution
      inequality was calculated using the Gini coefficient. Indices for local spatial
      autocorrelation were measured at the OD level using geographical information
      system (GIS) analysis. Finally, a potential link between socioeconomic status and
      resource distribution was explored by mapping resource densities against poverty
      rates. RESULTS: Gini coefficient calculation revealed variable inequality in
      distribution of the five key resources at the Province and OD levels. A greater
      percentage of the population resides in areas of relative under-supply (28.5%)
      than over-supply (21.3%). Areas with more resources per capita showed significant
      clustering in central Cambodia while areas with fewer resources clustered in the
      northern and western provinces. Hospital-based inpatient beds, doctors, and
      nurses were most heavily concentrated in areas of the country with the lowest
      poverty rates; however, beds and nurses in Non-Hospital Medical Facilities (NHMF)
      showed increasing concentrations at higher levels of poverty. CONCLUSIONS: There
      is considerable heterogeneity in healthcare resource distribution across
      Cambodia. Distribution mapping at the local level can inform policy decisions on
      where to stockpile resources in advance of and for reallocation in the event of a
      pandemic. These findings will be useful in determining future health resource
      investment, both for pandemic preparedness and for general health system
      strengthening, and provide a foundation for future analyses of equity in health
      services provision for pandemic mitigation planning in Cambodia.

PMID- 24090287
TI  - Long-term outcomes after nucleos(t)ide analogues discontinuation in chronic
      hepatitis B patients with HBeAg-negative.
AB  - BACKGROUND: Hepatitis B e Antigen (HBeAg)-negative chronic hepatitis B (CHB)
      patients have an active liver disease with a high risk of progression to
      decompensated cirrhosis and hepatocellular carcinoma. The management strategy for
      HBeAg-negative CHB patients treated with nucleos(t)ide analogues (NUCs) is a
      topic of concern. To observe the outcomes for this population after NUCs
      withdrawal, HBeAg-negative CHB patients with loss of hepatitis B surface antigen
      (HBsAg) or sustained undetectable HBV DNA levels who had discontinued NUCs
      therapy were included in the study. METHODS: A total of 66 patients (2 patients
      with HBsAg loss and 64 patients with sustained undetectable HBV DNA levels) were
      examined. HBV DNA levels and alanine aminotransferase (ALT) levels were monitored
      regularly after discontinuation of NUCs therapy. Relapse was defined as HBV DNA
      levels >2,000 IU/mL while off therapy in at least two determinations more than 4
      weeks apart. RESULTS: The time to achieve undetectable HBV DNA levels was 14
      weeks (interquartile range (IQR): 12-24 weeks). The time until consolidation
      therapy was 144 weeks (IQR: 96-168 weeks). No relapses occurred in either of the
      HBsAg loss patients. Among the 64 patients with undetectable HBV DNA levels, 19
      (29.7%) patients demonstrated evidence of relapse. All the relapses occurred
      within 96 weeks after discontinuation. The median duration of relapse was 36
      weeks (IQR: 12-48 weeks). Elevation of HBV DNA and ALT levels over baseline was
      only observed in 10% of the relapse patients. There were no significant
      differences among the baseline characteristics (sex, HBV genotype, age, or ALT
      level) or the time until consolidation therapy between relapse and sustained
      response patients. CONCLUSIONS: NUC discontinuation is feasible after achieving
      undetectable HBV DNA levels in HBeAg-negative CHB patients. Prolonging the time
      until consolidation therapy may be a good strategy to decrease the rate of
      relapse. More than 96 weeks of sustained response is a predictive marker of long
      term sustained response.

PMID- 24090288
TI  - Melatonin: its possible role in the management of viral infections--a brief
      review.
AB  - Melatonin, a versatile molecule, is synthesized by the pineal gland but also by
      other organs, including gastrointestinal tract, retina, thymus, bone marrow, and
      by leukocytes. Besides playing an important role in various functions of the
      body, including sleep and circadian rhythm regulation, melatonin also shows
      immunoregulatory, free radical scavenger and antioxidant functions. Because of
      these latter characteristics melatonin has also been found to be effective in
      fighting viral infections in a variety of experimental animal and in vitro
      studies. These data suggest a possible therapeutic potential of melatonin in
      human virus-induced disorders. 

PMID- 24090289
TI  - Potentiation of a novel palladium (II) complex lethality with bee venom on the
      human T-cell acute lymphoblastic leukemia cell line (MOLT-4).
AB  - BACKGROUND: Although honeybee venom (BV) has been reported to induce apoptosis in
      different types of cancerous cells, its synergistic effects with customary anti
      cancer drugs remain largely unknown. In the present study, we evaluated the
      cytotoxic effect of BV alone (as a natural product) and the synergistic
      cytological effects of this component in combination with [Pd (bpy) (Pi
      Pydtc)]NO3 - a novel palladium complex on human T-cell lymphoblastic leukemia
      cells. To investigate the cytotoxic effect of the BV alone and in combination
      with palladium complex on MOLT-4 cells MTT assay was performed. In order to
      determine the apoptotic effects of BV separately and in combination with Pd (II)
      complex on these cells and its ability to induce apoptosis, morphological
      examination, flowcytometric analysis and caspase-3 colorimetric assay were done.
      RESULTS: We found that BV induced morphological changes, namely nuclear
      shrinkage, and inhibited MOLT-4 cell proliferation; both effects were dose- and
      time-dependent. Flow cytometry by Annexin-V antibody demonstrated that BV induced
      apoptosis in MOLT-4 cells. Furthermore, BV induced apoptosis independently of
      caspase-3 in these cells. In addition, we proved a clear synergistic effect of BV
      on [Pd (bpy) (Pi-Pydtc)]NO3. The apoptotic pathway activated by BV in combination
      with Pd complex was caspase-3-dependent. CONCLUSIONS: These observations provide
      an explanation for the anti-proliferative properties of BV, and suggest that this
      agent may be useful for treating lymphoblastic leukemia alone or in combination
      with chemotherapy drugs pending further investigations on animal models as
      preclinical tests.

PMID- 24090291
TI  - Taking evidence-based nursing practice to the next level.

PMID- 24090290
TI  - Modification of spasticity by transcutaneous spinal cord stimulation in
      individuals with incomplete spinal cord injury.
AB  - CONTEXT/OBJECTIVE: To examine the effects of transcutaneous spinal cord
      stimulation (tSCS) on lower-limb spasticity. DESIGN: Interventional pilot study
      to produce preliminary data. SETTING: Department of Physical Medicine and
      Rehabilitation, Wilhelminenspital, Vienna, Austria. PARTICIPANTS: Three subjects
      with chronic motor-incomplete spinal cord injury (SCI) who could walk >=10 m.
      INTERVENTIONS: Two interconnected stimulating skin electrodes (O 5 cm) were
      placed paraspinally at the T11/T12 vertebral levels, and two rectangular
      electrodes (8 * 13 cm) on the abdomen for the reference. Biphasic 2 ms-width
      pulses were delivered at 50 Hz for 30 minutes at intensities producing
      paraesthesias but no motor responses in the lower limbs. OUTCOME MEASURES: The
      Wartenberg pendulum test and neurological recordings of surface-electromyography
      (EMG) were used to assess effects on exaggerated reflex excitability. Non
      functional co-activation during volitional movement was evaluated. The timed 10-m
      walk test provided measures of clinical function. RESULTS: The index of
      spasticity derived from the pendulum test changed from 0.8 +/- 0.4 pre- to 0.9 +/
      0.3 post-stimulation, with an improvement in the subject with the lowest pre
      stimulation index. Exaggerated reflex responsiveness was decreased after tSCS
      across all subjects, with the most profound effect on passive lower-limb movement
      (pre- to post-tSCS EMG ratio: 0.2 +/- 0.1), as was non-functional co-activation
      during voluntary movement. Gait speed values increased in two subjects by 39%.
      CONCLUSION: These preliminary results suggest that tSCS, similar to epidurally
      delivered stimulation, may be used for spasticity control, without negatively
      impacting residual motor control in incomplete SCI. Further study in a larger
      population is warranted.

PMID- 24090292
TI  - Investigating factors associated with quality of life of vitiligo patients in
      Singapore.
AB  - Skin disease is often visible to others. People who have dermatological condition
      may also suffer from its psychological consequences. The purpose of this study is
      to explore the quality of life of patients with vitiligo and to identify factors
      associated with their quality of life. A descriptive correlational study was
      conducted with 222 patients with vitiligo recruited from two skin centres in
      Singapore from 2009 to 2011. Data were collected by a structured questionnaire.
      Three outcome variables were measured in the study: predisposal, clinical and
      psychological outcomes. Results showed that almost two-thirds of the participants
      reported vitiligo had moderate to extreme impact on their quality of life.
      Multiple regression analyses showed that patients who were depressed, had thyroid
      disease and had not used multiclear treatment were more likely to report poor
      quality of life. It is recommended that providing health care consultation for
      patients with vitiligo may help reduce depressive symptoms and maintain their
      psychological health, thus enhance their quality of life. 

PMID- 24090293
TI  - Safe venepuncture techniques using a vacuum tube system.
AB  - The purpose of this study was to determine safe techniques of performing blood
      collection using an evacuated tube system, particularly with regard to
      manipulation of the equipment and at the puncture site. Careful observation of
      the procedure was used to collect data for evaluating the various venepuncture
      techniques. Nurses were digitally videotaped performing simulated venepuncture. A
      self-administered questionnaire and unstructured observation of a videotaped
      recording were evaluated, and valid responses were analyzed from participants who
      performed venepuncture using various techniques. The participants who changed
      hands during the procedure were older than those who did not change hands. Needle
      movements during puncture and insertion, including rotation and insertion in a
      wave-like trajectory, were observed. Appropriate training, including
      recommendations for maintaining the stability of the needle tip, is important to
      ensure safety when performing venepuncture. Movement of the needle should not
      place too much pressure on the puncture site. 

PMID- 24090294
TI  - The effects of audiovisual distraction on children's pain during laceration
      repair.
AB  - This study aimed to determine the effects of audiovisual distraction on pain in
      children during laceration repair in emergency room settings. This study was
      designed as a randomized controlled trial. Eighty-four children aged 3-10 years
      were randomized to either the experimental group or the control group. Pain
      response was assessed by the Faces Pain Rating Scale, a visual analogue scale and
      the Procedure Behaviour Checklist. We measured salivary cortisol levels as a
      physiological pain response. The results showed that the sensory and affective
      pain responses were significantly lower in magnitude in the experimental group
      than in the control group. There was no statistically significant difference in
      physiological pain responses between the two groups. Audiovisual distraction
      might be a helpful method to reduce children's pain during laceration repair in
      emergency room settings. 

PMID- 24090295
TI  - Change of glycaemic control and predictors in diabetes patients: longitudinal
      observational study during the one year after hospital discharge.
AB  - Glycated haemoglobin (HbA1c) might reflect glycaemic control in persons with
      diabetes. Study aims were to identify changes in glycated haemoglobin values and
      predictors (baseline coping behaviour, fasting plasma glucose, disease-related
      and demographic factors) in patients during 1 year after hospital discharge. A
      longitudinal prospective design with convenience sampling was used. Subjects were
      recruited from a community hospital in Taiwan. Measures included Jalowiec Coping
      Scale, fasting plasma glucose, HbA1c values, and demographics. Generalized
      estimating equation was used to determine factors of change in glycated
      haemoglobin. A total of 57 patients completed 1 year of follow-up. Half did not
      receive diabetes mellitus education and regular exercise. Patients' glycated
      haemoglobin levels follow controls at 6 months after discharge. Patients with
      higher levels of blood glucose, less problem-focused coping and greater emotion
      focused coping were associated with poor glycaemic control. Education programmes
      should involve individual-centred care and health behaviours for prevention of
      diabetes complications. 

PMID- 24090296
TI  - An e-health intervention for increasing diabetes knowledge in African Americans.
AB  - An evidence-based e-health program, eCare We Care, was developed to disseminate
      information on diabetes management through web-based interactive tutorials. This
      study examined the effect of the eCare We Care program on diabetes knowledge
      development in African American adults with low diabetes literacy. Forty-six
      African American adults with type 1 or type 2 diabetes and low diabetes literacy
      were recruited from two health-care centres in eastern Winston Salem, North
      Carolina. The eCare We Care program included four weekly sessions: introduction
      to diabetes; eye complications; foot care; and meal planning. Significant
      differences in scores on the diabetes knowledge survey were demonstrated between
      the eCare We Care program participants and the comparison group. Study findings
      indicate the eCare We Care program is more effective in improving diabetes
      knowledge of African American adults with low diabetes literacy than paper-based,
      text-only tutorials. The eCare We Care program can be an effective educational
      strategy for improving diabetes knowledge and decreasing diabetes disparities
      among African American adults. 

PMID- 24090297
TI  - Patterns of complementary and alternative medicine use among a group of patients
      with type 2 diabetes receiving outpatient care in Singapore.
AB  - This study aims to identify patterns and evaluate factors associated with
      complementary and alternative medicine (CAM) use among type 2 diabetes patients
      in Singapore. A cross-sectional descriptive study using a self-administered
      questionnaire was performed among type 2 diabetes patients at an outpatient
      diabetes centre, and participants' medical records were accessed for diabetes
      complications and conventional medicine for managing diabetes. Among 304
      participants, 43.4% used CAM and 61.2% did not inform health-care professionals
      of their CAM use. Three most common CAM were nutritional supplements, Chinese
      herbal medicine and massage. Friends (44.2%), partner and family (38%) were top
      sources of information for CAM, whereas factors significantly associated with CAM
      use were gender (P = 0.049), total monthly household income (P = 0.048) and
      frequency of self-monitoring of blood glucose (P = 0.036). Results highlight a
      need for improved health-care professionals-patients communication and for health
      care professionals to be educated on CAM to provide relevant education to
      patients.

PMID- 24090298
TI  - Degree of ambulation and factors associated with the median distance moved per
      day in Alzheimer's disease patients.
AB  - The Integrated Circuit tag monitoring system became available to measure
      wandering in terms of the distance moved by dementia patients. The purposes of
      the study were to describe degree of ambulation in patients with Alzheimer's
      disease (AD) and to examine factors associated with the distance moved. AD
      patients were recruited at a dementia care unit in Asakayama Hospital, Osaka,
      Japan. The monitoring system generated the distance moved per day. Demographic
      and clinical data were abstracted from medical records. Mini-Mental State
      Examination was used to measure cognitive function. A multiple linear regression
      was used to predict the distance moved per day. The research was approved by the
      ethics committee of the university and the hospital, and written informed consent
      was obtained from the patients' proxies. Majority of the AD subjects monitored
      had moderate to advance stage of dementia. Patients' age and cognitive function
      were predictors of the median distance moved/day, and these two variables
      explained almost half of the variance. Older age and lower cognitive function
      were associated with reduced median distance moved per day in AD patients. 

PMID- 24090299
TI  - Behaviour of pregnant women towards the use of prenatal care services: a
      comparative study between China and the Democratic Republic of Congo.
AB  - The present study aims to highlight and describe the elements of difference
      and/or similarity between China (Changchun) and the Democratic Republic of Congo
      (Kinshasa) concerning the behaviour of pregnant women in the use of prenatal care
      services. A cross-sectional investigation with a self-designed survey was carried
      out from September 2011 to March 2012 among pregnant women attending antenatal
      visits in Changchun and Kinshasa. Sixty pregnant women of childbearing age, with
      an uncomplicated pregnancy, attending prenatal visits in two hospitals and two
      community care centres were eligible for the study. Data were analysed using SPSS
      13.0 software. Kinshasa 86.6% vs. Changchun 26.6% of pregnant women attended
      prenatal health education. In Changchun none of the responders (0%) have received
      tetanus vaccine, whereas in Kinshasa 90% were vaccinated against tetanus.
      Kinshasa 73.3% vs. Changchun 23.3% of pregnant women confirmed that they have
      performed the HIV test. The elements of difference found in our results were
      statistically significant P < 0.05. Prenatal health education can help pregnant
      women to have an appropriate awareness and improve their behaviour in the use of
      prenatal care services.

PMID- 24090300
TI  - Implementation of evidence-based nursing practice for diabetic patients: an
      Iranian experience.
AB  - Evidence-based nursing is recognized as an indicator of quality in nursing
      practice, a basis for accountability and the gold standard of professional
      nursing care. The aim of this study was to explore nurses' experiences and
      perceptions about evidence-based nursing practice in giving care to patients with
      diabetic foot ulcers. A qualitative research design was adopted, and content
      analysis was used to analyse data. Semistructured interviews were held with 19
      bachelor-degree nurses working in a teaching hospital in an urban area of Iran.
      During data analysis, two main themes developed: 'structural backgrounds of the
      organization' and 'empowerment'. Accordingly, it was concluded that successful
      implementation of evidence-based nursing requires the reconfiguration of the
      administrative structure in the hospital. In addition, it requires the support of
      nurse leaders to facilitate the implementation of evidence-based nursing in the
      practice. 

PMID- 24090301
TI  - Using nursing practice guidelines for the prevention of multidrug-resistant
      tuberculosis among hospitalized adult patients in Bangladesh.
AB  - Multidrug-resistant tuberculosis (MDR-TB) is one of the major public health
      concerns worldwide particularly in developing countries, including Bangladesh.
      Thus far, there are no well-validated clinical guidelines for the prevention of
      MDR-TB. This study aims to evaluate the improvement in nurses' practice using the
      newly developed Nursing Practice Guidelines for the Prevention of MDR-TB (NPG:
      MDR-TB) among hospitalized adult patients in Bangladesh. The guidelines were
      developed, disseminated and evaluated among 64 nurses by assessing nursing
      practice for the prevention of MDR-TB during pre- and postimplementation of the
      guidelines. Significant differences between pretest and post-test mean scores of
      nursing practice for the prevention of MDR-TB in case finding and case holding
      were found in three levels of wards, including Level 0 (non-TB), Level 1 (TB) and
      Level 2 (MDR-TB) (P < 0.001). This indicated that the guidelines might be
      applicable to reduce the development of MDR-TB in hospitals. However, this was a
      preliminary study with a limited time frame. Further evaluation is, therefore,
      needed.

PMID- 24090302
TI  - Factors associated with stress of conscience among emergency medical technicians
      in China.
AB  - The current study was designed to investigate factors related to stress of
      conscience among emergency medical technicians in China. One hundred and seventy
      five doctors and nurses from emergency departments completed questionnaires
      measuring demographic information, two personality traits (i.e. responsibility
      and logical-affective orientation), stress of conscience and colleagues' stress
      of conscience. Important findings include the following: (i) Stress of conscience
      varied as a function of age, years of work, and marital status; (ii)
      Participants' stress of conscience was highly associated with colleagues' stress
      of conscience; and (iii) Both responsibility and a logical orientation were
      negatively associated with stress of conscience. 

PMID- 24090303
TI  - The short form of the revised almost perfect scale.
AB  - We created a shorter and more refined item set from the Almost Perfect Scale
      Revised (APS-R; Slaney, Mobley, Trippi, Ashby, & Johnson, 1996; Slaney, Rice,
      Mobley, Trippi, & Ashby, 2001) to measure 2 major dimensions of perfectionism:
      standards (high performance expectations) and discrepancy (self-critical
      performance evaluations). In Study 1, after testing the internal structure of the
      measure (N = 749), a subset of the current APS-R items was derived (Short Almost
      Perfect Scale [SAPS]) that possessed good psychometric features, such as strong
      item-factor loadings, score reliability, measurement invariance between women and
      men, and criterion-related validity through associations with neuroticism,
      conscientiousness, academic performance, and depression. Controlling for
      neuroticism and conscientiousness, factor mixture modeling supported a 2-factor,
      3-class model of perfectionism, and results were consistent with labeling the
      classes as nonperfectionists and adaptive and maladaptive perfectionists.
      Measurement results were cross-validated in a separate sample (N = 335). Study 2
      also provided substantial evidence for the convergent, discriminant, and
      criterion-related validity of SAPS scores. Both studies supported the SAPS as a
      brief and psychometrically strong measure of major perfectionism factors and
      classes of perfectionists. 

PMID- 24090304
TI  - The 372 T/C genetic polymorphism of TIMP-1 as a biomarker of mortality in
      patients with sepsis.

PMID- 24090305
TI  - An unusual fragmentation of oxetane-embedded tetracyclic ketal systems.
AB  - An unusual route for the synthesis of functionalized cyclobutane derivatives
      starting from functionalized norbornane derivatives is reported. Base-induced
      fragmentation of an oxetanol-type moiety embedded in a tetracyclic norbornyl
      ketal leads to a cyclobutane-fused derivative as the major or exclusive product.
      The fragmentation reaction for bridgehead-bromine-substituted derivatives was
      much faster than for the corresponding chlorine-substituted substrates. The
      functionalized cyclobutane product was formed exclusively in high yield in the
      former case, while the latter furnished a minor uncyclized side product in
      varying yields. 

PMID- 24090306
TI  - Chemical modifications of peptide sequences via S-alkylation reaction.
AB  - A chemoselective, convenient, and mild synthetic strategy to modify peptides on a
      cysteine sulfhydryl group is described. It simply requires activated molecular
      sieves to selectively promote S-alkylation in the presence of peptide
      nucleophilic functionalities. The procedure is easy to perform, fast, and
      provides high yields even in the case of poor electrophilic groups. Moreover, the
      method allows an efficient one-pot poly alkylation, proving that the sulfhydryl
      reactivity does not rely on its specific position within the peptide sequence. 

PMID- 24090307
TI  - Capecitabine in the treatment of esophageal and gastric cancers.
AB  - INTRODUCTION: Fluoropyrimidine therapy has been a mainstay in the treatment of
      cancers of the esophagus and stomach for nearly half of a century in the form of
      intravenous 5-fluorouracil. Capecitabine , an oral fluoropyrimidine precursor,
      was first approved in 2001 for the treatment of metastatic colon cancer and may
      be used interchangeably with parenteral 5-FU in the treatment of upper
      gastrointestinal (GI) cancers. AREAS COVERED: In this article, mechanisms of
      action and synergy with other systemic therapies and radiation are reviewed. A
      summary of the most important clinical trial results shaping the use of
      capecitabine in the treatment of cancers of the esophagus and stomach is offered,
      along with an update of upcoming areas of interest using this agent in these
      disease types. EXPERT OPINION: Improvements in understanding molecular mechanisms
      of disease, defining distinct disease subtypes based on histology, genetic
      background and levels of protein expression as well as signaling pathways may
      start to clarify the reasons underlying heterogeneous clinical behaviors and
      different outcomes between patients with seemingly similar tumor types.
      Capecitabine ushered in the era of oral chemotherapy, providing ease of
      administration with comparable if not superior efficacy to its older parental
      counterpart. The best way to fully exploit its potential in gastroesophageal
      cancers is being actively studied worldwide at all stages of disease management.

PMID- 24090308
TI  - Electronic structures and spin density distributions of BrO2 and (HO)2BrO
      radicals. Mechanisms for avoidance of hypervalency and for spin delocalization
      and spin polarization.
AB  - The results are reported of an ab initio study of bromine dioxide BrO2, 1, and of
      the T-shaped trans- and cis-dihydroxides 2 and 3 of dihydrogen bromate (HO)2BrO.
      The thermochemistry has been explored of potential synthetic routes to (HO)2BrO
      involving water addition to BrO2, hydroxyl addition to bromous acid HOBrO, 4,
      protonation/reduction of bromic acid HOBrO2, 5, via tautomers 6-8 of protonated
      bromic acid, and by reduction/protonation of bromic acid via radical anion
      [HOBrO2](-), 9. The potential energy surface analyses were performed at the
      MP2(full)/6-311G* level (or better) and with the consideration of aqueous
      solvation at the SMD(MP2(full)/6-311G*) level (or better), and higher-level
      energies were computed at levels up to QCISD(full,T)/6-311++G(2df,2pd)//MP2. The
      addition of RO radical to bromous acid or bromite esters and the reduction of
      protonated bromic acid or protonated bromate esters are promising leads for
      possible synthetic exploration. Spin density distributions and molecular
      electrostatic potentials were computed at the QCISD(full)/6-311G*//MP2(full)/6
      311G* level to characterize the electronic structures of 1-3. Both radicals
      employ maximally occupied (pseudo) pi-systems to transfer electron density from
      bromine to the periphery. While the formation of the (3c-5e) pi-system suffices
      to avoid hypervalency in 1, the formation of the (4c-7e) pi-system in 2 or 3
      still leaves the bromine formally hypervalent and (HO)2BrO requires
      delocalization of bromine density into sigma*-SMOs over the trans O-Br-O moiety.
      Molecular orbital theory is employed to describe the mechanisms for the avoidance
      of hypervalency and for spin delocalization and spin polarization. The (4c-7e) pi
      system in 2 is truly remarkable in that it contains five pi-symmetric spin
      molecular orbitals (SMO) with unique shapes. 

PMID- 24090309
TI  - Behavioral and clinical correlates of serum bilirubin concentrations in Japanese
      men and women.
AB  - BACKGROUND: A considerable interest has been drawn to potential protective
      effects of bilirubin against oxidative stress-related diseases. Smoking is known
      to be associated with lower concentrations of serum bilirubin, but other
      behavioral correlates of serum bilirubin have not been well studied. In this
      cross-sectional study, we examined the associations of behavioral and clinical
      factors with serum total bilirubin in Japanese men and women. METHOD: The study
      subjects comprised of 4802 men and 6414 women aged 49-76 years who participated
      in the baseline survey of an ongoing cohort study on lifestyle-related diseases
      in Fukuoka, Japan. With consideration to time of the day of blood sampling and
      fasting hours, the associations with smoking, alcohol intake, body mass index,
      physical activity, coffee, tea, blood pressure, glycated hemoglobin (HbA1c), HDL
      cholesterol and non-HDL cholesterol with serum bilirubin were evaluated by
      analysis of covariance and multiple linear regression analysis. RESULTS: While
      smoking was negatively associated with serum bilirubin, alcohol consumption was
      positively associated with serum bilirubin in both men and women. Coffee
      consumption was associated with lower bilirubin concentrations in both sexes. In
      the multiple linear regression analysis, HDL cholesterol was positively and HbA1c
      was negatively associated with bilirubin in both men and women, and the
      associations were more evident in women. CONCLUSION: Smoking, alcohol use and
      coffee consumption were important behavioral correlates of serum bilirubin in
      Japanese men and women. Serum HDL cholesterol was a measurable clinical correlate
      of bilirubin in women.

PMID- 24090310
TI  - Squaramide-catalyzed enantioselective Michael addition of masked acyl cyanides to
      substituted enones.
AB  - Masked acyl cyanide (MAC) reagents are shown to be effective umpolung synthons
      for enantioselective Michael addition to substituted enones. The reactions are
      catalyzed by chiral squaramides and afford adducts in high yields (90-99%) and
      with excellent enantioselectivities (85-98%). The addition products are unmasked
      to produce dicyanohydrins that, upon treatment with a variety of nucleophiles,
      provide gamma-keto acids, esters, and amides. The use of this umpolung synthon
      has enabled, in enantiomerically enriched form, the first total synthesis of the
      prenylated phenol (+)-fornicin C. 

PMID- 24090311
TI  - Discovery of novel small-molecule inhibitors of BRD4 using structure-based
      virtual screening.
AB  - Bromodomains (BRDs) are epigenetic readers that recognize acetylated-lysine (KAc)
      on proteins and are implicated in a number of diseases. We describe a virtual
      screening approach to identify BRD inhibitors. Key elements of this approach are
      the extensive design and use of substructure queries to compile a set of
      commercially available compounds featuring novel putative KAc mimetics and
      docking this set for final compound selection. We describe the validation of this
      approach by applying it to the first BRD of BRD4. The selection and testing of
      143 compounds lead to the discovery of six novel hits, including four
      unprecedented KAc mimetics. We solved the crystal structure of four hits,
      determined their binding mode, and improved their potency through synthesis and
      the purchase of derivatives. This work provides a validated virtual screening
      approach that is applicable to other BRDs and describes novel KAc mimetics that
      can be further explored to design more potent inhibitors. 

PMID- 24090312
TI  - 3D time series analysis of cell shape using Laplacian approaches.
AB  - BACKGROUND: Fundamental cellular processes such as cell movement, division or
      food uptake critically depend on cells being able to change shape. Fast
      acquisition of three-dimensional image time series has now become possible, but
      we lack efficient tools for analysing shape deformations in order to understand
      the real three-dimensional nature of shape changes. RESULTS: We present a
      framework for 3D+time cell shape analysis. The main contribution is three-fold:
      First, we develop a fast, automatic random walker method for cell segmentation.
      Second, a novel topology fixing method is proposed to fix segmented binary
      volumes without spherical topology. Third, we show that algorithms used for each
      individual step of the analysis pipeline (cell segmentation, topology fixing,
      spherical parameterization, and shape representation) are closely related to the
      Laplacian operator. The framework is applied to the shape analysis of neutrophil
      cells. CONCLUSIONS: The method we propose for cell segmentation is faster than
      the traditional random walker method or the level set method, and performs better
      on 3D time-series of neutrophil cells, which are comparatively noisy as stacks
      have to be acquired fast enough to account for cell motion. Our method for
      topology fixing outperforms the tools provided by SPHARM-MAT and SPHARM-PDM in
      terms of their successful fixing rates. The different tasks in the presented
      pipeline for 3D+time shape analysis of cells can be solved using Laplacian
      approaches, opening the possibility of eventually combining individual steps in
      order to speed up computations.

PMID- 24090313
TI  - The importance of caregivers in the outcome of pediatric HIV management, Mombasa,
      Kenya.
AB  - We assessed programmatic gaps that prevent the optimal treatment of pediatric HIV
      infection despite free antiretroviral care in Kenya. Of 626 HIV-infected Kenyan
      children, the median age was five years, 54% were male and the mortality rate was
      3.2 per 100 person-years. A total of 380 (61%) children initiated antiretroviral
      therapy (ART) during the study period. Among the 246 children who never started
      ART, 129 (52%) met the criteria for ART initiation. Immunologic failure occurred
      in 20% of children who received ART for >24 weeks. In multivariate analysis,
      immunological failure was associated with having nonimmediate relative or
      unrelated caregivers accompanying the child to clinic (AOR = 69.16, p = 0.008).
      Having >= 3 types of accompanying caregivers was also associated with virologic
      failure in multivariate analysis (AOR = 3.84, p = 0.03). The lost to follow-up
      rate was 8.7/100 persons-years for the entire cohort, and significantly higher
      (17.7/100 persons-years) among children not on ART (p < 0.001). Among children
      who do initiate ART, those with the best treatment outcomes were those who had a
      limited number of close relatives as caregivers and good adherence to ART. Focus
      on early ART initiation and education of the right caregiver will likely improve
      retention and quality of pediatric HIV care in Kenya.

PMID- 24090316
TI  - Bladder calculi formed over a hair nidus in spinal injury cases.
AB  - Clean intermittent catheterization has been demonstrated to be a safe and
      effective method of bladder drainage in patients with neurogenic bladder
      dysfunction. However, breakdowns in technique may allow the introduction of
      foreign matter into the bladder and thereby result in bladder calculi. The three
      cases reported herein demonstrate this potential problem in persons with spinal
      cord injury (SCI) with hair nidus as the source of bladder calculi causing
      neurogenic bladder. In each situation, the problem was identified, calculi were
      removed cystoscopically and the patient and/or the ancillary aid were
      reinstructed. We recommend annual renal function tests, ultrasound and cytoscopic
      screening in high suspicion cases to allow early detection of bladder calculi in
      persons with SCI and prevent further urinary tract infections. This report also
      emphasizes the need for patient education and a careful follow-up preventing
      bladder calculi and thus, minimizing the morbidity in persons with SCI. 

PMID- 24090317
TI  - Diagnostic and prognostic potential of the macrophage specific receptor CD163 in
      inflammatory diseases.
AB  - CD163 is a scavenger receptor for the endocytosis of hemoglobin and
      hemoglobin/haptoglobin complexes and is nearly exclusively expressed on monocytes
      and macrophages. CD163 is induced by IL-10 and glucocorticoids while
      proinflammatory cytokines like TNF reduce its expression. The cytokine IL-6 which
      exerts pro- and anti-inflammatory effects depending on the signaling pathway
      activated strongly upregulates CD163. Anti-inflammatory cells involved in the
      down-modulation of inflammation express high CD163 which controls immune
      response. Ligands of the toll-like receptors 2, 4 and 5 stimulate ectodomain
      shedding of CD163 thereby releasing soluble CD163 (sCD163) which mediates
      cellular uptake of free hemoglobin. Soluble CD163 circulates in blood and is
      increased in serum of critically ill patients, in chronic inflammatory and
      infectious diseases. Serum concentrations of sCD163 are related to disease
      severity and are suitable biomarkers for diagnosis, prognosis and therapeutic
      drug monitoring in several inflammatory disorders. Raised sCD163 even predicts
      comorbidity and mortality in some diseases. Relationship of CD163/sCD163 and
      disease severity demonstrates a fundamental role of monocytes/macrophages in
      various diseases. CD163 is a target to specifically deliver drugs to macrophages
      intending advanced therapeutic efficiency and minimization of adverse reactions.
      In this review article factors regulating CD163 expression and shedding, current
      knowledge on the function of CD163 and sCD163, and inflammatory diseases where
      CD163 and/or sCD163 are mostly increased are summarized. 

PMID- 24090320
TI  - The antibiotic crisis: charting Australia's path towards least resistance.

PMID- 24090319
TI  - Survey assessment on pediatricians' attitudes on head lice management.
AB  - BACKGROUND: Pediculosis capitis is a worldwide health problem. One of the most
      important factor in effective head lice eradication is to ensure that infestation
      is adequately recognized and treated. Our survey investigated the knowledge and
      practice among primary care Italian pediatricians regarding to the prevention and
      treatment of head lice. METHODS: The questionnaire was distributed to all the
      pediatricians registered at the Annual Congress of Practice in Pediatrics held in
      Florence, Italy, November 11-12, 2011. It includes 10 questions in a multiple
      choice format, and one answer for each question was provided. The questionnaire
      was conceived by pediatricians at the Infectious Disease Unit of the Department
      of Science for the Health of Woman and Child, University of Florence. Questions
      were designed according to the guidelines by the Italian Pediatric Society (SIP),
      and international guidelines, such as the Centers for Disease Control and
      Prevention (CDC), and the American Academy of Pediatrics (AAP). RESULTS: Overall,
      364/600 pediatricians (60.7% of physicians registered to the Congress) returned
      the questionnaire. The majority of them (232/364; 63,7%) believe that parents
      consult their primary care pediatrician only after the failure of other
      "remedies". Mostly, they prescribe Malathion (116/364, 31,8%) as first line
      treatment. Two-hundred-fourty-three (66.7%) of participants consider creams,
      foams and gels the most effective formulations. Two-hundred-sixty-two of
      pediatricians interviewed (72.0%) suggest to repeat the treatment after one week,
      37/364 (10.2%) after two weeks. The majority of the pediatricians interviewed
      reported that recurrences occur in less than 30% of cases (279/364; 76,6%). In
      their own opinion, most of recurrences are the consequence of a reinfestation in
      the community (259/264; 77%). Three-hundred-thirty-four (91.7%) of them have
      never prescribed oral therapy for the treatment of head lice. Finally, 289/364
      (79.4%) pediatricians believe that no product is effective for prevention.
      CONCLUSIONS: This is the first study that investigates the clinical practice of
      family pediatricians about the management and treatment of head lice globally,
      the Italian pediatricians surveyed proved to be quite informed on the head lice
      management. However, even in a country where pediatric assistance is free for
      everybody, a considerable proportion of parents do not seek advice to their own
      family pediatrician. Therefore, educations of parents, other than continuous
      updating of pediatricians, may contribute to a better management of head lice in
      the community.

PMID- 24090321
TI  - Challenges in managing patients in Australia with chronic hepatitis B: the
      General Practitioners' perspective.
AB  - OBJECTIVE: General Practitioners (GPs) are essential to reducing the impact of
      chronic hepatitis B (CHB) given their clinical management role where only 56% of
      people with the infection in Australia have been diagnosed. This qualitative
      study aimed to identify the challenges GPs face in effectively responding to CHB.
      METHODS: Semi-structured interviews were conducted with 26 GPs self-identifying
      as having a 'high caseload' of patients and/or a particular interest in CHB.
      Participants were recruited from five jurisdictions and came from diverse
      ethnicities, clinical experience and practice profile. Interview data were
      analysed according to the principles of grounded theory. RESULTS: Patient and GP
      knowledge, a lack of community awareness, and language and cultural diversity
      impeded the GP response to CHB. Communication with specialists was reported as
      challenging with unclear referral pathways, limited feedback from specialists
      after referral, and poor liaison and support for managing people living with CHB.
      Regulations restricting GPs capacity to respond included the lack of prescribing
      opportunities, fear of Medicare auditing for screening the populations most at
      risk, and inadequate financial support given the complexity of CHB and the
      communities most affected by the infection. CONCLUSIONS: General Practitioners
      require additional skills and resources to support the effective management of
      people with CHB. These include improved awareness and knowledge about the
      infection, adequate financial resources to support patient management, and
      effective referral pathways and support.

PMID- 24090322
TI  - Developing an evidence-based guideline for the management of exposure to
      hepatitis B at a Victorian tertiary hospital.
AB  - OBJECTIVE: To develop a guideline for the management of potential exposures to
      hepatitis B virus (HBV) at The Alfred Hospital, based on results of clinical
      audit, database analysis and literature review. METHODS: i) Retrospective record
      review of all histories of patients who received HBV immunoglobulin (HBIG) at The
      Alfred between 1/1/2007 and 30/9/2011. ii) Analysis of HBV serological results of
      men who have sex with men (MSM) on Victorian NPEP Service (VNPEPS) database
      between 10/8/2005 and 31/12/2011. iii) Literature review to determine risks of
      HBV transmission and best practice for prevention of HBV transmission. RESULTS: A
      total of 48 patients were potentially exposed to HBV and given HBIG, with sexual
      exposure the most common indication (n=20). The source was reported to be HBsAg
      positive in one case only. Of the MSM on the VNPEPS database, 63% were immune to
      HBV, and only 0.5% of patients tested had evidence of chronic HBV infection. The
      recommendations for use of HBIG in The Australian Immunisation Guidelines are
      ambiguous and differ from other international guidelines. CONCLUSION: This audit
      at a tertiary referral hospital identified problems with the management of those
      potentially exposed to HBV. In those non-immune patients exposed to HBV, the
      combination of HBIG plus vaccination provides the best protection against
      infection. The risk of transmission of HBV is highly variable; rates of chronic
      HBV in PWID and MSM in Australia are low and do not warrant use of HBIG unless
      the source is known to be HBsAg positive.

PMID- 24090323
TI  - The burden of chronic hepatitis B virus infection in Australia, 2011.
AB  - OBJECTIVE: The number of Australians living with chronic hepatitis B (CHB) is
      thought to be increasing, as are adverse outcomes including cirrhosis and liver
      cancer, however, robust, up-to-date estimates of this burden are limited.
      Contemporary estimates of the prevalence of CHB in Australia are essential to
      guide appropriate public health and clinical responses. METHODS: This study used
      census-based methodology attributing risk of CHB by country of birth and
      Aboriginal and Torres Strait Islander status, augmented with priority risk-group
      based estimates. Deterministic mathematical modelling was used for comparison and
      for validation of census-derived estimates. RESULTS: An estimated 218,000
      Australians (plausible range 192,000-284,000) are living with CHB, a significant
      increase over previous estimates. The prevalence derived using mathematical
      modelling was similar, at 204,000. Notable differences were observed by
      geographic area in both prevalence and the populations predominantly affected. It
      is estimated that only 56% of people living with CHB in Australia have been
      diagnosed and notified. CONCLUSIONS: The prevalence of CHB in Australia is
      increasing, with 1% of the population now estimated to be affected. The majority
      of the burden is experienced by people born overseas in endemic areas, with more
      than 95% of new cases of CHB entering the population through migration.
      IMPLICATIONS: It is imperative that more attention and greater resources are
      devoted to addressing CHB in Australia; to increase the proportion of Australians
      affected who have been diagnosed and who are on treatment, in accordance with the
      First National Hepatitis B Strategy.

PMID- 24090324
TI  - Measles transmission by 'fly-in fly-out' workers in Australia.
AB  - OBJECTIVE: To describe the outbreak investigation and control measures for a
      cluster of measles cases involving 'fly-in fly-out' (FIFO) workers on an off
      shore industrial vessel. METHODS: Following Australian guidelines, measles cases
      were interviewed and at-risk contacts on the Australian mainland received measles
      vaccine, immunoglobulin or health advice. For the industrial vessel: (i) exposed
      FIFO workers who had already left the vessel received health advice through their
      employer; (ii) workers remaining on the vessel were offered measles vaccine; and
      (iii) FIFO workers joining the vessel for 21 days following the prodrome onset of
      the last case of measles on the vessel were offered measles vaccine. Measles
      virus isolates were sent for genotype determination. RESULTS: Four measles cases
      from two Australian jurisdictions were epidemiologically linked to the
      retrospectively identified index case, a New Zealand FIFO worker. No further
      cases were detected following the institution of outbreak control measures.
      CONCLUSION: FIFO workers congregating on large industrial projects are a discrete
      risk group with the potential to spread infectious diseases over large distances,
      both domestically and internationally. IMPLICATIONS: FIFO workers' immunisation
      history should be reviewed prior to deployment. Catch-up vaccination, where
      appropriate, would minimise transmission of vaccine-preventable diseases such as
      measles and help maintain a healthy, productive workforce.

PMID- 24090326
TI  - "We need our own food, to grow our own veggies..." Remote Aboriginal food gardens
      in the Top End of Australia's Northern Territory.
AB  - OBJECTIVE: Remote Aboriginal community gardens (gardens) frequently operate below
      their full potential. A set of gardening sustainability principles may improve
      their planning, operation and long-term sustainability. This paper aims to
      document the principles of sustainability of non-profit remote Aboriginal
      community gardens in the Top End of the Northern Territory. METHODS: Throughout
      2011, gardens in the Top End of the Northern Territory were visited. Interviews
      and observational data were used to explore the principles of garden
      sustainability with participants. Subsequent iterative thematic analysis informed
      development of a set of gardening sustainability principles. RESULTS: Principles
      of sustainability included effective garden planning; community autonomy,
      consultation and engagement; growing community vetted crops; employing long-term,
      effective, culturally sensitive managers; long-term, transparent funding
      organisations and cycles; garden integration into existing food supply chains;
      culturally appropriate employment arrangements; and physical aspects of
      successful gardening. CONCLUSIONS: This work uniquely consults gardeners,
      managers and Aboriginal and non-Aboriginal people of both genders in the largest
      reported study of its type, resulting in new and expanded findings, particularly
      including new social factors for gardening success. IMPLICATIONS: Expanding the
      understanding of what makes gardens work to include the important social factors
      identified here may have merit.

PMID- 24090325
TI  - Low seroprevalence of Murray Valley encephalitis and Kunjin viruses in an
      opportunistic serosurvey, Victoria 2011.
AB  - OBJECTIVE: To assess evidence of recent and past exposure to Murray Valley
      encephalitis virus (MVEV) and West Nile clade Kunjin virus (KUNV) in residents of
      the Murray Valley, Victoria, during a period of demonstrated activity of both
      viruses in early 2011. METHODS: A cross-sectional serosurvey using two
      convenience samples: stored serum specimens from a diagnostic laboratory in
      Mildura and blood donors from the Murray Valley region. Specimens were collected
      between April and July 2011. The main outcome measure was total antibody (IgM and
      IgG) reactivity against MVEV and KUNV measured using an enzyme immunoassay and
      defined as inhibiting binding of monoclonal antibodies by >50%, when compared to
      negative controls. Evidence of recent exposure was measured by the presence of
      MVEV and KUNV IgM detected by immunofluorescence. RESULTS: Of 1,115 specimens, 24
      (2.2%, 95% CI 1.3-3.0%) were positive for MVEV total antibody, and all were
      negative for MVEV IgM. Of 1,116 specimens, 34 (3.1%, 95% CI 2.0-4.0%) were
      positive for KUNV total antibody, and 3 (0.27%) were KUNV IgM positive. Total
      antibody seroprevalence for both viruses was higher in residents born before
      1974. CONCLUSIONS: Despite widespread MVEV and KUNV activity in early 2011, this
      study found that seroprevalence of antibodies to both viruses was low (<5%) and
      little evidence of recent exposure. IMPLICATIONS: Our findings suggest both
      viruses remain epizootic in the region and local residents remain potentially
      susceptible to future outbreaks.

PMID- 24090327
TI  - Statistical methods to enhance reporting of Aboriginal Australians in routine
      hospital records using data linkage affect estimates of health disparities.
AB  - OBJECTIVE: To investigate under-recording of Aboriginal people in hospital data
      from New South Wales (NSW), Australia, define algorithms for enhanced reporting,
      and examine the impact of these algorithms on estimated disparities in
      cardiovascular and injury outcomes. METHODS: NSW Admitted Patient Data were
      linked with NSW mortality data (2001-2007). Associations with recording of
      Aboriginal status were investigated using multilevel logistic regression. The
      number of admissions reported as Aboriginal according to six algorithms was
      compared with the original (unenhanced) Aboriginal status variable. Age
      standardised admission, and 30- and 365-day mortality ratios were estimated for
      cardiovascular disease and injury. RESULTS: Sixty per cent of the variation in
      recording of Aboriginal status was due to the hospital of admission, with poorer
      recording in private and major city hospitals. All enhancement algorithms
      increased the number of admissions reported as Aboriginal, from between 4.1% and
      37.8%. Admission and mortality ratios varied markedly between algorithms, with
      less strict algorithms resulting in higher admission rate ratios, but generally
      lower mortality rate ratios, particularly for cardiovascular disease.
      CONCLUSIONS: The choice of enhancement algorithm has an impact on the number of
      people reported as Aboriginal and on estimated outcome ratios. The influence of
      the hospital on recording of Aboriginal status highlights the importance of
      continued efforts to improve data collection. IMPLICATIONS: Estimates of
      Aboriginal health disparity can change depending on how Aboriginal status is
      reported. Sensitivity analyses using a number of algorithms are recommended.

PMID- 24090328
TI  - The Grog Mob: lessons from an evaluation of a multi-disciplinary alcohol
      intervention for Aboriginal clients.
AB  - OBJECTIVES: To evaluate a 12-month trial of an evidence-based non-residential
      treatment program for Indigenous clients with alcohol problems, offering three
      streams of care: pharmacotherapy, psychological and social support. METHODS:
      Process evaluation of program implementation; outcome evaluation of client
      outcomes. RESULTS:  IMPLEMENTATION: despite constraints of time and remoteness,
      the trial demonstrated the feasibility of implementing such a program. The
      medical stream generated fewer pharmacotherapy prescriptions than expected. The
      most active stream was the psychological therapy stream. OUTCOMES: between March
      2008 and April 2009, 129 clients were referred to the program, of whom 49
      consented to have de-identified data used for the evaluation. Of these, 19
      clients received one or more streams of care, 15 of whom (78.9%) subsequently
      stopped or reduced drinking. However, among the remaining 30 consenting clients
      who had not received an intervention, 70.0% also reported stopping or reducing
      drinking. The evidence of program effectiveness is therefore equivocal and
      evaluation over a longer period is required. CONCLUSION AND IMPLICATIONS: The
      trial demonstrated the viability of, and demand for, evidence-based non
      residential treatment for Indigenous clients with alcohol problems. Reasons
      behind an apparent reluctance among GPs to prescribe pharmacotherapy for
      Indigenous clients, and steps to overcome this, need further attention.

PMID- 24090329
TI  - A qualitative evaluation of a mentoring program for Aboriginal health workers and
      allied health professionals.
AB  - OBJECTIVE: Effective partnerships between Aboriginal Health Workers and non
      Aboriginal health professionals are essential to achieve Aboriginal health
      outcomes. This study aimed to evaluate a mentoring workforce development strategy
      for Aboriginal Health Workers and non-Aboriginal allied health professionals.
      METHODS: Thirty-four Aboriginal Health Workers and non-Aboriginal health
      professionals were recruited to the mentoring program where they were paired and
      established a learning relationship for approximately six months. A qualitative
      evaluation with thirty of the participants was undertaken involving in-depth
      interviews at the completion of the program. RESULTS: A total of 18 mentoring
      partnerships were formed across Victoria. The data revealed three key themes in
      relation to the evaluation of the program: (1) The mentoring program facilitated
      two-way learning, (2) The Aboriginal Health Workers and non-Aboriginal health
      professional participants reported being able to meet their identified learning
      needs through the partnership, (3) The capacity to improve practice was
      facilitated through readiness to learn and change practice and personal
      attributes of the participants, as well as organisation and management support.
      CONCLUSIONS: Peer mentoring between Aboriginal and non-Aboriginal health
      workforce was found to be a powerful mechanism to promote two-way learning that
      has the capacity to meet learning needs and promote practice improvement.
      IMPLICATIONS: Peer mentoring may be part of a multi-strategy approach to the
      development of the Aboriginal health workforce.

PMID- 24090330
TI  - Pacific peoples three months after injury: a comparison of outcomes between
      Pacific and non-Pacific participants in a NZ cohort study.
AB  - OBJECTIVES: To: describe pre-injury characteristics of Pacific (n=239) and non
      Pacific (n=2,611) participants and compare their outcomes three months after
      injury. METHODS: Participants were New Zealand residents aged 18-64 years
      referred to the Accident Compensation Corporation's injury entitlement claims
      register. Univariate and multivariable analyses compared pre-injury and injury
      related characteristics of Pacific and non-Pacific people and assessed the
      unadjusted and adjusted relative risks for selected outcomes. RESULTS: Of the
      2,856 participants, 239 identified at least one Pacific ethnicity. Adjusted
      relative risks (aRR; 95% confidence intervals) for Pacific peoples, with the non
      Pacific group as the reference, indicate Pacific peoples were: less likely to
      have no/lesser problems with disability (aRR=0.82; 0.70,0.95); less likely to
      have no problems with EQ-5D self-care (aRR=0.88; 0.80,0.98); less likely not to
      report EQ-5D anxiety/depression (aRR=0.84; 0.76,0.93); and less satisfied with
      social relationships three months after injury (aRR=0.89; 0.83,0.95).
      CONCLUSIONS: Evidence does not suggest Pacific peoples' likelihood of paid
      employment differs from non-Pacific people three months after injury. However,
      Pacific peoples appear to have an increased likelihood of problems with
      disability, self-care, anxiety/depression and social relationships. IMPLICATIONS:
      This study provides information about a range of previously unknown outcomes
      following injury for Pacific peoples in New Zealand, and suggests areas of
      possible focus for health and rehabilitation service providers and policy-makers
      interested in improving outcomes for injured Pacific peoples.

PMID- 24090331
TI  - Preventing child unintentional injury deaths: prioritizing the response to the
      New Zealand Child and Adolescent Injury Report Card.
AB  - OBJECTIVE: To develop recommendations for child unintentional injury prevention
      by comparing New Zealand's child unintentional injury mortality and injury
      prevention policies with those of European countries. METHODS: Unintentional
      child injury death rates based on external cause of injury were calculated and
      ranked. NZ's score for each of the 12 domains (based on external causes of
      injury) from the New Zealand Child and Adolescent Report Card was compared to
      European scoring. Policy priorities are identified by domains where mortality
      makes up a high proportion of overall child unintentional injury mortality (high
      burden of injury) and where report card score for that domain is low in
      comparison to other countries (under-utilisation of effective interventions).
      RESULTS: Death as a motor vehicle occupant accounts for 49% of all child
      unintentional injury deaths, followed by pedestrian (10%) and drowning deaths
      (8%). The overall score for the 12 policy domains of the NZ Report Card ranks NZ
      as 15(th) among the 25 European countries. There are important policy and
      legislative actions which NZ has not implemented. CONCLUSIONS: A number of
      evidence-based injury prevention policy and legislative actions are available
      that could target areas of greatest childhood injury mortality in NZ.
      IMPLICATIONS: A set of injury prevention policy and legislation priorities are
      presented which, if implemented, would result in a significant reduction in the
      injury mortality and morbidity rates of NZ children.

PMID- 24090332
TI  - Public say food regulatory policies to improve health in Western Australia are
      important: population survey results.
AB  - OBJECTIVE: To investigate the level of support among Western Australian adults
      for food control policies to improve diet, reduce obesity and protect the
      environment. METHODS: Attitudes towards government food control policies on food
      labelling, food advertising, and the supply of environmentally friendly food data
      were pooled from two Nutrition Monitoring Survey Series telephone surveys of
      2,147 adults aged 18-64 years collected in 2009 and 2012. Descriptive and
      logistic regression analyses were conducted using survey module of STATA 12.
      RESULTS: The majority of adults believe it is important that government regulates
      food policy options under consideration: nutrition information on food labels
      (97% versus 2% who think it is not important); health rating on food labels (95%
      versus 3%); food advertising (83% versus 11%); and the supply of environmentally
      friendly food (86% versus 9%). CONCLUSIONS: Community perception is that
      government control or regulation of food labelling, food advertising and the
      supply of environmentally friendly food is important. IMPLICATIONS: Curbing
      excess weight gain and related disease burden is a public health priority.
      Australian governments are considering food regulatory interventions to assist
      the public to improve their dietary intake. These findings should provide
      reassurance to government officials considering these regulatory measures.

PMID- 24090333
TI  - Regulatory responses to over-the-counter codeine analgesic misuse in Australia,
      New Zealand and the United Kingdom.
AB  - OBJECTIVE: Analysis of the policy response by Australia's National Drugs and
      Poisons Schedule Committee (NDPSC) and comparison with recommendations by expert
      advisory committees in New Zealand and the United Kingdom. METHODS: Analysis of
      public policy documents of relevant regulatory authorities was conducted. Data
      were extracted regarding changes to over-the-counter (OTC) codeine analgesic
      scheduling, indications, maximum unit dose, maximum daily dose, maximum pack
      size, warning labels, consumer medicine information and advertising. Where
      available, public submissions and other issues considered by the committees and
      rationale for their recommendations were recorded and thematically analysed.
      RESULTS: Expert advisory committees in Australia, NZ and the UK defined the
      policy problem of OTC codeine misuse and harm as small relative to total use and
      responded by restricting availability. Pharmacist supervision was required at the
      point-of-sale and pack sizes were reduced to short-term use. CONCLUSIONS:
      Comparison with recommendations by expert advisory committees in NZ and the UK
      suggests the NDPSC's actions in response to OTC codeine misuse were appropriate
      given the available evidence of misuse and harm, but highlights opportunities to
      utilise additional regulatory levers. IMPLICATIONS: Framing policy problems as
      matters of public health in the context of limited evidence may support decision
      makers to implement cautionary incremental policy change.

PMID- 24090334
TI  - Community pharmacy influenza immunisation increases vaccine uptake and gains
      public approval.

PMID- 24090335
TI  - The risk of being diagnosed with cancer.

PMID- 24090336
TI  - Gender equity in health policy: response to Keleher.

PMID- 24090337
TI  - Prostate cancer screening for men aged 75 to 84 years in New South Wales.

PMID- 24090338
TI  - 'Legislative scaffolding': a new approach to prevention.

PMID- 24090340
TI  - Porous graphitic carbon loading ultra high sulfur as high-performance cathode of
      rechargeable lithium-sulfur batteries.
AB  - Porous graphitic carbon of high specific surface area of 1416 m(2) g(-1) and high
      pore volume of 1.11 cm(3) g(-1) is prepared by using commercial CaCO3
      nanoparticles as template and sucrose as carbon source followed by 1200  degrees
      C high-temperature calcination. Sulfur/porous graphitic carbon composites with
      ultra high sulfur loading of 88.9 wt % (88.9%S/PC) and lower sulfur loading of
      60.8 wt % (60.8%S/PC) are both synthesized by a simple melt-diffusion strategy,
      and served as cathode of rechargeable lithium-sulfur batteries. In comparison
      with the 60.8%S/PC, the 88.9%S/PC exhibits higher overall discharge capacity of
      649.4 mAh g(-1)(S-C), higher capacity retention of 84.6% and better coulombic
      efficiency of 97.4% after 50 cycles at a rate of 0.1C, which benefits from its
      remarkable specific capacity with such a high sulfur loading. Moreover, by using
      BP2000 to replace the conventional acetylene black conductive agent, the 88.9%
      S/PC can further improve its overall discharge capacity and high rate property.
      At a high rate of 4C, it can still deliver an overall discharge capacity of 387.2
      mAh g(-1)(S-C). The porous structure, high specific surface area, high pore
      volume and high electronic conductivity that is originated from increased
      graphitization of the porous graphitic carbon can provide stable electronic and
      ionic transfer channel for sulfur/porous graphitic carbon composite with ultra
      high sulfur loading, and are ascribed to the excellent electrochemical
      performance of the 88.9%S/PC. 

PMID- 24090339
TI  - Highway proximity associated with cardiovascular disease risk: the influence of
      individual-level confounders and exposure misclassification.
AB  - BACKGROUND: Elevated cardiovascular disease risk has been reported with proximity
      to highways or busy roadways, but proximity measures can be challenging to
      interpret given potential confounders and exposure error. METHODS: We conducted a
      cross sectional analysis of plasma levels of C-Reactive Protein (hsCRP),
      Interleukin-6 (IL-6), Tumor Necrosis Factor alpha receptor II (TNF-RII) and
      fibrinogen with distance of residence to a highway in and around Boston,
      Massachusetts. Distance was assigned using ortho-photo corrected parcel matching,
      as well as less precise approaches such as simple parcel matching and geocoding
      addresses to street networks. We used a combined random and convenience sample of
      260 adults >40 years old. We screened a large number of individual-level
      variables including some infrequently collected for assessment of highway
      proximity, and included a subset in our final regression models. We monitored
      ultrafine particle (UFP) levels in the study areas to help interpret proximity
      measures. RESULTS: Using the orthophoto corrected geocoding, in a fully adjusted
      model, hsCRP and IL-6 differed by distance category relative to urban background:
      43% (-16%,141%) and 49% (6%,110%) increase for 0-50 m; 7% (-39%,45%) and 41%
      (6%,86%) for 50-150 m; 54% (-2%,142%) and 18% (-11%,57%) for 150-250 m, and 49% (
      4%, 131%) and 42% (6%, 89%) for 250-450 m. There was little evidence for
      association for TNF-RII or fibrinogen. Ortho-photo corrected geocoding resulted
      in stronger associations than traditional methods which introduced differential
      misclassification. Restricted analysis found the effect of proximity on
      biomarkers was mostly downwind from the highway or upwind where there was
      considerable local street traffic, consistent with patterns of monitored UFP
      levels. CONCLUSION: We found associations between highway proximity and both
      hsCRP and IL-6, with non-monotonic patterns explained partly by individual-level
      factors and differences between proximity and UFP concentrations. Our analyses
      emphasize the importance of controlling for the risk of differential exposure
      misclassification from geocoding error.

PMID- 24090341
TI  - Sequential preconcentration and on-membrane Raman determination of carboxylic
      single-walled carbon nanotubes in river water samples.
AB  - This article proposes a simple and sensitive approach for the preconcentration
      and determination of carboxylated single-walled carbon nanotubes (c-SWNTs) in
      environmental samples using membranes modified with multiwalled carbon nanotubes
      (MWNTs). The method is based on the preconcentration of c-SWNTs and their direct
      on-filter Raman spectroscopic analysis. The preconcentration of c-SWNTs is
      performed by microfiltrating the sample through a cellulose membrane modified
      with MWNTs fabricated from a surfactant dispersion of the same. The analytes are
      retained in the membrane through pi-pi interactions with MWNTs forming the
      membrane. The G-/D-band ratio of the carbon nanotubes has been used as an
      analytical parameter to quantify the presence of c-SWNTs, which mainly contribute
      to the intensity of the G band. The limit of detection was found to be 1 MUg.L(
      1), and the precision, for a 10 MUg.L(-1) concentration of c-SWNTs, was 4.74%
      intramembrane and 6.3% intermembrane. The optimized procedure was successfully
      applied to the determination of traces of c-SWNTs in river water samples. 

PMID- 24090342
TI  - Discriminative ability of the three functional tests in independent ambulatory
      patients with spinal cord injury who walked with and without ambulatory assistive
      devices.
AB  - BACKGROUND/OBJECTIVES: Many persons with spinal cord injury (SCI) require an
      ambulatory assistive device (AAD). An effective monitoring method enables the use
      of an appropriate AAD and promotes levels of independence for patients. This
      study investigated the discriminative ability of the three-functional tools
      relating to walking ability, including the 10-meter walk test (10MWT), the five
      times sit-to-stand test (FTSST), and the timed up and go test (TUGT), in
      independent ambulatory persons with SCI who walked with walker, crutches, cane,
      and non-AAD. METHODS: Eighty-five persons with SCI who could perform sit-to-stand
      and walk independently at least 50 m were cross-sectionally assessed for their
      functional ability using the 10MWT, FTSST, and TUGT. RESULTS: The findings for
      persons not using AADs were significantly better than the other groups for every
      test (P < 0.001). In addition, persons who walked with cane were significantly
      different from those who used walkers (P < 0.001) but there were no significant
      differences between persons who used walker and crutches for every test (P >
      0.05). CONCLUSION: The findings supported the discriminative validity of the
      tools, allowing them to indicate functional changes in persons with SCI who walk
      with different AADs. However, the non-significant differences between subjects
      who used a walker and crutches may relate to the method of subject arrangement
      and inclusion criteria that recruit subjects with rather good walking capability
      and lower limb function. The findings may also suggest the use of the sit-to
      stand maneuver as a simple screening tool for walking advancement of walker
      users, pending further investigation.

PMID- 24090343
TI  - Prevalence of Clostridium difficile colonization among healthcare workers.
AB  - BACKGROUND: Clostridium difficile infection (CDI) has increased to epidemic
      proportions in recent years. The carriage of C. difficile among healthy adults
      and hospital inpatients has been established. We sought to determine whether C.
      difficile colonization exists among healthcare workers (HCWs) in our setting.
      METHODS: A point prevalence study of stool colonization with C. difficile among
      doctors, nurses and allied health staff at a large regional teaching hospital in
      Geelong, Victoria. All participants completed a short questionnaire and all stool
      specimens were tested by Techlab(r) C.diff Quik Check enzyme immunoassay followed
      by enrichment culture. RESULTS: Among 128 healthcare workers, 77% were female, of
      mean age 43 years, and the majority were nursing staff (73%). Nineteen HCWs (15%)
      reported diarrhoea, and 12 (9%) had taken antibiotics in the previous six weeks.
      Over 40% of participants reported having contact with a patient with known or
      suspected CDI in the 6 weeks before the stool was collected. C. difficile was not
      isolated from the stool of any participants. CONCLUSION: Although HCWs are at
      risk of asymptomatic carriage and could act as a reservoir for transmission in
      the hospital environment, with the use of a screening test and culture we were
      unable to identify C. difficile in the stool of our participants in a non
      outbreak setting. This may reflect potential colonization resistance of the gut
      microbiota, or the success of infection prevention strategies at our institution.

PMID- 24090344
TI  - Assessment of pretend play in preschool-aged children: validation and factor
      analysis of the affect in play scale-preschool version.
AB  - The Affect in Play Scale-Preschool (APS-P) and Affect in Play Scale-Preschool
      Brief Rating (APS-P-BR) versions assess cognitive and affective play processes
      during a 5-min standardized play task. In this study, construct validity,
      external validity, and factor analyses for each scale were examined in 107
      preschoolers. Reliability and validity were supported. Unlike results found with
      school-aged samples, positive affect loaded with the cognitive variables on
      factor analyses of the APS-P and APS-P-BR, suggesting that negative and undefined
      affect might represent a separate factor in preschool-aged children.
      Developmental significance and implications for use of the 2 scoring versions are
      discussed. 

PMID- 24090345
TI  - Probing with the ventilator.
AB  - Neurally adjusted ventilatory assist operates through recordings of electrical
      activity of the diaphragm (EAdi). Barwing and colleagues found increases in EAdi
      in weaning-failure patients, although the values were not significantly different
      from weaning-success patients. Future studies will need to carefully control for
      the considerable biological noise evident in EAdi recordings. 

PMID- 24090346
TI  - Influenza infection control guidance provided to staff at Veterans Affairs
      facilities for veterans with spinal cord injury during a pandemic(?).
AB  - CONTEXT/OBJECTIVE: To assess guidance provided to staff at Veterans Affairs (VA)
      healthcare facilities on H1N1 influenza infection control for veterans with
      spinal cord injuries and disorders (SCI/D). STUDY DESIGN: Cross-sectional
      qualitative semi-structured interviews. SETTING: Thirty-three VA healthcare
      facilities from throughout the United States that provide care to veterans with
      SCI/D. PARTICIPANTS: Thirty-three infection control key informants, each
      representing a VA healthcare facility. INTERVENTIONS: None. OUTCOME MEASURES:
      Infection control practices, including vaccination practices, hospital
      preparedness, and recommendations for future pandemics, both in general and
      specifically to SCI/D. RESULTS: Most (n = 26, 78.8%) infection control key
      informants believed veterans with SCI/D were at increased risk for influenza and
      complications, but only 17 (51.5%) said veterans with SCI/D were treated as a
      priority group for vaccination at their facilities. There was little special
      guidance provided for treating veterans with SCI/D, and most (n = 28, 84.8%)
      informants said that infection control procedures and recommendations were
      applied universally. Yet, 10 key informants discussed 'unique challenges' to
      infection control in the SCI/D population. Informants discussed the potential for
      infectious agents to be spread through shared and common use equipment and the
      necessity of including caregivers in any vaccination or educational campaigns.
      CONCLUSION: Greater input by experts knowledgeable about SCI/D is recommended to
      adequately address pandemic influenza within healthcare facilities where
      individuals with SCI/D receive care.

PMID- 24090347
TI  - Design, synthesis, and biological evaluation of indole-2-carboxamides: a
      promising class of antituberculosis agents.
AB  - Indole-2-carboxamides have been identified as a promising class of
      antituberculosis agents from phenotypic screening against mycobacteria. One of
      the hits, indole-2-carboxamide analog (1), had low micromolar potency against
      Mycobacterium tuberculosis (Mtb), high mouse liver microsomal clearance, and low
      aqueous solubility. Structure-activity relationship studies revealed that
      attaching alkyl groups to the cyclohexyl ring significantly improved Mtb activity
      but reduced solubility. Furthermore, chloro, fluoro, or cyano substitutions on
      the 4- and 6-positions of the indole ring as well as methyl substitution on the
      cyclohexyl ring significantly improved metabolic stability. 39 and 41, the lead
      candidates, displayed improved in vitro activity compared to most of the current
      standard TB drugs. The low aqueous solubility could not be mitigated because of
      the positive correlation of lipophilicity with Mtb potency. However, both
      compounds displayed favorable oral pharmacokinetic properties in rodents and
      demonstrated in vivo efficacy. Thus, indole-2-carboxamides represent a promising
      new class of antituberculosis agents. 

PMID- 24090348
TI  - Wnt6 is required for maxillary palp formation in Drosophila.
AB  - BACKGROUND: Wnt6 is an evolutionarily ancient member of the Wnt family. In
      Drosophila, Wnt6 loss-of-function animals have not yet been reported, hence
      information about fly Wnt6 function is lacking. In wing discs, Wnt6 is expressed
      at the dorsal/ventral boundary in a pattern similar to that of wingless, an
      important regulator of wing size. To test whether Wnt6 also contributes towards
      wing size regulation, we generated Wnt6 knockout flies. RESULTS: Wnt6 knockout
      flies are viable and have no obvious defect in wing size or planar cell polarity.
      Surprisingly, Wnt6 knockouts lack maxillary palps. Interestingly, Wnt6 is absent
      from the genome of hemipterans, correlating with the absence of maxillary palps
      in these insects. CONCLUSIONS: Wnt6 is important for maxillary palp development
      in Drosophila, and phylogenetic analysis indicates that loss of Wnt6 may also
      have led to loss of maxillary palps on an evolutionary time scale.

PMID- 24090349
TI  - Nitric oxide interaction with oxy-coboglobin models containing trans-pyridine
      ligand: two reaction pathways.
AB  - The oxy-cobolglobin models of the general formula (Py)Co(Por)(O2) (Por = meso
      tetraphenyl- and meso-tetra-p-tolylporphyrinato dianions) were constructed by
      sequential low-temperature interaction of Py and dioxygen with microporous layers
      of Co-porphyrins. At cryogenic temperatures small increments of NO were
      introduced into the cryostat and the following reactions were monitored by the
      FTIR and UV-visible spectroscopy during slow warming. Similar to the recently
      studied (NH3)Co(Por)(O2) system (Kurtikyan et al. J. Am. Chem. Soc., 2012, 134,
      13671-13680), this interaction leads to the nitric oxide dioxygenation reaction
      with the formation of thermally unstable nitrato complexes (Py)Co(Por)(eta(1)
      ONO2). The reaction proceeds through the formation of the six-coordinate
      peroxynitrite adducts (Py)Co(Por)(OONO), as was demonstrated by FTIR measurements
      with the use of isotopically labeled (18)O2, (15)NO, N(18)O, and (15)N(18)O
      species and DFT calculations. In contrast to the ammonia system, however, the
      binding of dioxygen in (Py)Co(Por)(O2) is weaker and the second reaction pathway
      takes place due to autoxidation of NO by rebound O2 that in NO excess gives N2O3
      and N2O4 species adsorbed in the layer. This leads eventually to partial
      formation of (Py)Co(Por)(NO) and (Py)Co(Por)(NO2) as a result of NO and NO2
      reactions with five-coordinate Co(Por)(Py) complexes that are present in the
      layer after the O2 has been released. The former is thermally unstable and at
      room temperature passes to the five-coordinate nitrosyl complex, while the latter
      is a stable compound. In these experiments at 210 K, the layer consists mostly of
      six-coordinate nitrato complexes and some minor quantities of six-coordinate
      nitro and nitrosyl species. Their relative quantities depend on the experimental
      conditions, and the yield of nitrato species is proportional to the relative
      quantity of peroxynitrite intermediate. Using differently labeled nitrogen oxide
      isotopomers in different stages of the process the formation of the caged radical
      pair after homolytic disruption of the O-O bond in peroxynitrite moiety is
      clearly shown. The composition of the layers upon farther warming to room
      temperature depends on the experimental conditions. In vacuo the six-coordinate
      nitrato complexes decompose to give nitrate anion and oxidized cationic complex
      Co(III)(Por)(Py)2. In the presence of NO excess, however, the nitro-pyridine
      complexes (Py)Co(Por)(NO2) are predominantly formed formally indicating the oxo
      transfer reactivity of (Py)Co(Por)(eta(1)-ONO2) with regard to NO. Using
      differently labeled nitrogen in nitric oxide and coordinated nitrate a plausible
      mechanism of this reaction is suggested based on the isotope distribution in the
      nitro complexes formed. 

PMID- 24090350
TI  - Local mechanical properties of electrospun fibers correlate to their internal
      nanostructure.
AB  - The properties of polymeric nanofibers can be tailored and enhanced by properly
      managing the structure of the polymer molecules at the nanoscale. Although
      electrospun polymer fibers are increasingly exploited in many technological
      applications, their internal nanostructure, determining their improved physical
      properties, is still poorly investigated and understood. Here, we unravel the
      internal structure of electrospun functional nanofibers made by prototype
      conjugated polymers. The unique features of near-field optical measurements are
      exploited to investigate the nanoscale spatial variation of the polymer density,
      evidencing the presence of a dense internal core embedded in a less dense
      polymeric shell. Interestingly, nanoscale mapping the fiber Young's modulus
      demonstrates that the dense core is stiffer than the polymeric, less dense shell.
      These findings are rationalized by developing a theoretical model and simulations
      of the polymer molecular structural evolution during the electrospinning process.
      This model predicts that the stretching of the polymer network induces a
      contraction of the network toward the jet center with a local increase of the
      polymer density, as observed in the solid structure. The found complex internal
      structure opens an interesting perspective for improving and tailoring the
      molecular morphology and multifunctional electronic and optical properties of
      polymer fibers. 

PMID- 24090351
TI  - Phosphonium-iodonium ylides with heteroatomic groups in the synthesis of
      annelated P-containing heterocycles.
AB  - The preparation and chemistry of novel sulfonyl- and phosphoryl-derived lambda(3)
      iodanes are reported. These compounds with three different heteroatoms attached
      to a negatively charged C atom represent potentially useful reagents that combine
      in one molecule the synthetic advantages of a phosphonium ylide and an iodonium
      salt. Specifically, they can react with a number of acetylenes, leading to
      hitherto unknown sulfonyl- and phosphoryl-substituted phosphinolines,
      phosphininothiophenes, and a novel type of annelated P-containing heterocycle-
      phosphininopyrazole.

PMID- 24090352
TI  - NRMT2 is an N-terminal monomethylase that primes for its homologue NRMT1.
AB  - NRMT (N-terminal regulator of chromatin condensation 1 methyltransferase) was the
      first eukaryotic methyltransferase identified to specifically methylate the free
      alpha-amino group of proteins. Since the discovery of this N-terminal
      methyltransferase, many new substrates have been identified and the modification
      itself has been shown to regulate DNA-protein interactions. Sequence analysis
      predicts one close human homologue of NRMT, METTL11B (methyltransferase-like
      protein 11B, now renamed NRMT2). We show in the present paper for the first time
      that NRMT2 also has N-terminal methylation activity and recognizes the same N
      terminal consensus sequences as NRMT (now NRMT1). Both enzymes have similar
      tissue expression and cellular localization patterns. However, enzyme assays and
      MS experiments indicate that they differ in their specific catalytic functions.
      Although NRMT1 is a distributive methyltransferase that can mono-, di- and tri
      methylate its substrates, NRMT2 is primarily a monomethylase. Concurrent
      expression of NRMT1 and NRMT2 accelerates the production of trimethylation, and
      we propose that NRMT2 activates NRMT1 by priming its substrates for
      trimethylation.

PMID- 24090353
TI  - Intersession reliability of thoracolumbar multisegmental motor responses.
AB  - STUDY DESIGN: Experimental design. Objective To determine test-retest reliability
      across sessions of the thoracolumbar multisegmental motor responses (MMR) in the
      upper and lower limbs of healthy subjects. Test-retest reliability of MMR has not
      been established or examined in previous studies. SETTINGS: Neuro Laboratory of
      the Texas Woman's University (School of Physical Therapy, Houston, TX, USA).
      METHODS: The MMR of 15 healthy subjects were tested over two sessions. T11-12
      vertebral segments were electrically stimulated using surface electrodes. MMR
      signals of the upper and lower limbs were recorded, using surface electrodes,
      from the upper extremity muscles (abductor pollicis brevis, flexor carpi
      radialis, biceps brachii, triceps brachii), and from the lower extremity muscles
      (vastus medialis obliqus, medial hamstring, soleus, tibialis anterior). The peak
      to-peak maximum amplitude and deflection latency were the dependent parameters.
      Data from the first session was compared with a second session (on a different
      day), using interclass correlation coefficient (ICC), to evaluate the reliability
      across sessions. In addition, data from the right limbs were compared with the
      left limbs. RESULTS: MMR of the right and left, upper and lower extremities were
      comparable between limbs in all subjects. Further, signals were highly correlated
      between days of testing (ICC = 0.58-0.99) and was not statistically different
      between the two sessions in the same subject. CONCLUSION: These results indicate
      that MMR studies could be useful for serial testing of patients with neurological
      disorders, such as spinal cord injuries and diseases.

PMID- 24090354
TI  - Reliability of pulse oximetry in hypoxic newborn pigs.
AB  - OBJECTIVE: The reliability of pulse oximetry in the lower SaO2-ranges has not
      been fully investigated. We wanted to investigate pulse oximeter performance in a
      pig model of perinatal asphyxia. METHODS: Asphyxia was induced in 22 newborn
      pigs. Pulse oximetry-values for SpO2, as well as SaO2 from blood gas analyses
      were recorded multiple times before, during and after asphyxiation. The
      relationship between SpO2 and SaO2 in normoxia and hypoxia in this model was
      quantified. Calculations were made for 5% increments of SaO2 increasing
      successively from >=95% to >=20%. RESULTS: The pigs became severely hypoxic,
      acidotic and hypotensive. The bias in the total data was +13.7 (p < 0.001), i.e.
      SpO2 was on average higher than SaO2 for the entire interval of SaO2. However,
      bias was not significantly different from zero in most SpO2-ranges. Accuracy and
      precision were considerably higher than stated by the manufacturer in all SpO2
      ranges, with both accuracy and precision increasing when SpO2-values down to 60%
      and lower were included. CONCLUSION: Pulse oximetry was less reliable at SaO2
      values below 60%. Tissue acidosis and reduced peripheral perfusion may have
      contributed to this. It is unknown whether the difference between SpO2 and SaO2
      is clinically relevant.

PMID- 24090355
TI  - Laboratorial training of examiners for using a visual caries detection system in
      epidemiological surveys.
AB  - BACKGROUND: In epidemiological surveys, a good reliability among the examiners
      regarding the caries detection method is essential. However, training and
      calibrating those examiners is an arduous task because it involves several
      patients who are examined many times. To facilitate this step, we aimed to
      propose a laboratory methodology to simulate the examinations performed to detect
      caries lesions using the International Caries Detection and Assessment System
      (ICDAS) in epidemiological surveys. METHODS: A benchmark examiner conducted all
      training sessions. A total of 67 exfoliated primary teeth, varying from sound to
      extensive cavitated, were set in seven arch models to simulate complete mouths in
      primary dentition. Sixteen examiners (graduate students) evaluated all surfaces
      of the teeth under illumination using buccal mirrors and ball-ended probe in two
      occasions, using only coronal primary caries scores of the ICDAS. As reference
      standard, two different examiners assessed the proximal surfaces by direct visual
      inspection, classifying them in sound, with non-cavitated or with cavitated
      lesions. After, teeth were sectioned in the bucco-lingual direction, and the
      examiners assessed the sections in stereomicroscope, classifying the occlusal and
      smooth surfaces according to lesion depth. Inter-examiner reproducibility was
      evaluated using weighted kappa. Sensitivities and specificities were calculated
      at two thresholds: all lesions and advanced lesions (cavitated lesions in
      proximal surfaces and lesions reaching the dentine in occlusal and smooth
      surfaces). RESULTS: Regarding the reproducibility, the mean (range) of kappa
      values was 0.781 (0.529-0.927) for occlusal surfaces, 0.568 (0.191-0.881) for
      smooth surfaces, and 0.844 (0.698-0.971) for proximal surfaces. Considering all
      lesions, sensitivity and specificity mean values were respectively 0.724 and
      0.844 for occlusal, 0.635 and 0.943 for smooth and 0.658 and 0.927 for proximal
      surfaces. For detecting advanced lesions, sensitivities and specificities were
      0.563 and 0.920 for occlusal, 0.670 and 0.985 for smooth, and 0.838 and 0.985 for
      proximal surfaces. CONCLUSION: The methodology purposed for training and
      calibration of several examiners designated for epidemiological surveys of dental
      caries in preschool children using the ICDAS is feasible, permitting the
      assessment of reliability and accuracy of the examiners previously to the
      survey's development.

PMID- 24090356
TI  - Women's choices regarding HIV testing, disclosure and partner involvement in
      infant feeding and care in a rural district of Malawi with high HIV prevalence.
AB  - The influence of HIV-related stigma on women's choices with regard to HIV
      testing, disclosure and partner involvement in infant feeding and care is not
      well understood in rural Malawi but may influence the risk of vertical HIV
      transmission and infant health. In a study of HIV-infected and -uninfected women
      in 20 rural locations in Zomba District, Malawi, mothers were questioned at 18-20
      months post-partum about these issues. Ten per cent of women claimed unknown HIV
      status in labour so HIV testing should be routinely offered in Labour & Delivery
      wards. HIV-infected women were somewhat less likely to disclose to their partners
      than HIV-uninfected women (89 and 97%, respectively; p = 0.007) or to be
      cohabiting with partners during pregnancy (74 and 86%, respectively; p = 0.03).
      Partners of women were less inclined to disclose their HIV testing or HIV status
      (49 and 66% of partners of HIV-infected and -uninfected women, respectively).
      Greater partner testing and disclosure may improve prevention of mother to child
      transmission of HIV (PMTCT) in this population. A majority of women were inclined
      to make feeding decisions on their own, whereas most felt that other health
      related decisions should also involve the father. Most mothers believe that
      exclusive breast feeding (EBF) is the best infant feeding method (for the first
      six months) but it was actually practiced by a minority of women (20% of HIV
      infected and 5% of HIV-uninfected mothers; p = 0.01). EBF needs systematic
      support in order to be practised. 

PMID- 24090357
TI  - Synthesis of thiophene 1,1-dioxides and tuning their optoelectronic properties.
AB  - A 2,5-bis(tributylstannyl)thiophene 1,1-dioxide was prepared from 2,5
      bis(trimethylsilyl)thiophene 1,1-dioxide, bis(tributyltin) oxide, and
      tetrabutylammonium fluoride (TBAF). The 2,5-bis(tributylstannyl)thiophene 1,1
      dioxide and a 2,5-diiodothiophene 1,1-dioxide were utilized in a series of Stille
      cross-coupling reactions to afford thiophene 1,1-dioxides with either electron
      donating or electron-withdrawing substituents. Electron-withdrawing groups
      greatly facilitate the reduction of these sulfone heterocycles, and -C6H4-p-NO2
      substituents produce a 510 mV shift as compared to a thiophene 1,1-dioxide with
      two phenyl groups. 

PMID- 24090358
TI  - Observation of 4 nm pitch stripe domains formed by exposing graphene to ambient
      air.
AB  - We study epitaxial graphene on the 6H-SiC(0001) surface under ambient conditions
      using frequency-modulation atomic force microscopy. We observe large terraces
      with a self-assembled stripe structure within a highly adsorbate covered surface
      on top of the graphene. To identify the origin of the structure, we compare the
      experimental data on graphene with calculations and experiments on graphite that
      predict the formation of a solid-gas monolayer in the solid-liquid interface of
      hydrophobic surfaces. 

PMID- 24090359
TI  - Functional examination of MLH1, MSH2, and MSH6 intronic mutations identified in
      Danish colorectal cancer patients.
AB  - BACKGROUND: Germ-line mutations in the DNA mismatch repair genes MLH1, MSH2, and
      MSH6 predispose to the development of colorectal cancer (Lynch syndrome or
      hereditary nonpolyposis colorectal cancer). These mutations include disease
      causing frame-shift, nonsense, and splicing mutations as well as large genomic
      rearrangements. However, a large number of mutations, including missense, silent,
      and intronic variants, are classified as variants of unknown clinical
      significance. METHODS: Intronic MLH1, MSH2, or MSH6 variants were investigated
      using in silico prediction tools and mini-gene assay to asses the effect on
      splicing. RESULTS: We describe in silico and in vitro characterization of nine
      intronic MLH1, MSH2, or MSH6 mutations identified in Danish colorectal cancer
      patients, of which four mutations are novel. The analysis revealed aberrant
      splicing of five mutations (MLH1 c.588 + 5G > A, MLH1 c.677 + 3A > T, MLH1 c.1732
      2A > T, MSH2 c.1276 + 1G > T, and MSH2 c.1662-2A > C), while four mutations had
      no effect on splicing compared to wild type (MLH1 c.117-34A > T, MLH1 c.1039-8 T
      > A, MSH2 c.2459-18delT, and MSH6 c.3439-16C > T). CONCLUSIONS: In conclusion, we
      classify five MLH1/MSH2 mutations as pathogenic, whereas four MLH1/MSH2/MSH6
      mutations are classified as neutral. This study supports the notion that in
      silico prediction tools and mini-gene assays are important for the classification
      of intronic variants, and thereby crucial for the genetic counseling of patients
      and their family members.

PMID- 24090361
TI  - Improving the energy density and power density of CFx by mechanical milling: a
      primary lithium battery electrode.
AB  - The effect of high energy ball milling on the electrochemical performance of
      graphite fluoride (CFx) was investigated. A significant improvement was observed
      in both energy density and power density. The volumetric energy density was
      increased up to a factor of 3 with ball milled materials compared with pristine
      materials. The gravimetric energy density was increased up to a factor of 2,
      depending on the discharge rates. At 6C the ball milled material still delivered
      40% of its nominal capacity, whereas the pristine material did not exhibit any
      capacity any more. We achieved the power density of 9860 W/kg with a gravimetric
      energy density of 800 Wh/kg for the optimized material. 

PMID- 24090360
TI  - Developmental genes targeted for epigenetic variation between twin-twin
      transfusion syndrome children.
AB  - BACKGROUND: Epigenetic mechanisms are thought to be critical in mediating the
      role of the intrauterine environment on lifelong health and disease. Twin-twin
      transfusion syndrome (TTTS) is a rare condition wherein fetuses share the
      placenta and develop vascular anastomoses, which allow blood to flow between the
      fetuses. The unequal flow results in reciprocal hypo- and hypervolemia in the
      affected twins, striking growth differences and physiologic adaptations in
      response to this significant stressor. The donor twin in the TTTS syndrome can be
      profoundly growth restricted and there is likely a nutritional imbalance between
      the twins. The consequences of TTTS on fetal programming are unknown. This
      condition can now be effectively treated through the use of fetal laparoscopic
      procedures, but the potential for lifelong morbidity related to this condition
      during development is apparent. As this condition and the resulting
      uteroplacental discordance can play a role in the epigenetic process, we sought
      to investigate the DNA methylation profiles of childhood survivors of TTTS (n =
      14). We focused on differences in both global measures and genome-wide CpG
      specific DNA methylation between donor and recipient children in this pilot study
      in order to generate hypotheses for further research. RESULTS: We identified
      significant hypomethylation of the LINE1 repetitive element in the peripheral
      blood of donor children and subtle variation in the genome-wide profiles of CpG
      specific methylation most prominent at CpG sites which are targets for polycomb
      group repressive complexes. CONCLUSIONS: These preliminary results suggest that
      coordinated epigenetic alterations result from the intrauterine environment
      experienced by infants with TTTS and may, at least in part, be responsible for
      downstream health conditions experienced by individuals surviving this condition.

PMID- 24090362
TI  - Direct real-time detection of vapors from explosive compounds.
AB  - The real-time detection of vapors from low volatility explosives including PETN,
      tetryl, RDX, and nitroglycerine along with various compositions containing these
      substances was demonstrated. This was accomplished with an atmospheric flow tube
      (AFT) using a nonradioactive ionization source coupled to a mass spectrometer.
      Direct vapor detection was accomplished in less than 5 s at ambient temperature
      without sample preconcentration. The several seconds of residence time of
      analytes in the AFT provided a significant opportunity for reactant ions to
      interact with analyte vapors to achieve ionization. This extended reaction time,
      combined with the selective ionization using the nitrate reactant ions (NO3(-)
      and NO3(-).HNO3), enabled highly sensitive explosives detection from explosive
      vapors present in ambient laboratory air. Observed signals from diluted explosive
      vapors indicated detection limits below 10 ppqv using selected ion monitoring
      (SIM) of the explosive-nitrate adduct at m/z 349, 378, 284, and 289 for tetryl,
      PETN, RDX, and NG, respectively. Also provided is a demonstration of the vapor
      detection from 10 different energetic formulations sampled in ambient laboratory
      air, including double base propellants, plastic explosives, and commercial
      blasting explosives using SIM for the NG, PETN, and RDX product ions. 

PMID- 24090364
TI  - Replacement of Thr32 and Gln34 in the C-terminal neuropeptide Y fragment 25-36 by
      cis-cyclobutane and cis-cyclopentane beta-amino acids shifts selectivity toward
      the Y(4) receptor.
AB  - Neuropeptide Y (NPY) and pancreatic polypeptide (PP) control central and
      peripheral processes by activating the G protein coupled receptors YxR (x = 1, 2,
      4, 5). We present analogs of the C-terminal fragments 25-36 and 32-36 of NPY and
      PP containing (1R,2S)-cyclobutane (betaCbu) or (1R,2S)-cyclopentane (betaCpe)
      beta-amino acids, which display exclusively Y4R affinity. In particular,
      [betaCpe(34)]-NPY-(25-36) is a Y4R selective partial agonist (EC50 41 +/- 6 nM,
      Emax 71%) that binds Y4R with a Ki of 10 +/- 2 nM and a selectivity >100-fold
      relative to Y1R and Y2R and >50-fold relative to Y5R. Comparably, [Y(32),
      betaCpe(34)]-NPY(PP)-(32-36) selectively binds and activates Y4R (EC50 94 +/- 21
      nM, Emax 73%). The NMR structure of [betaCpe(34)]-NPY-(25-36) in
      dodecylphosphatidylcholine micelles shows a short helix at residues 27-32, while
      the C-terminal segment R(33)betaCpe(34)R(35)Y(36) is extended. The biological
      properties of the betaCbu- or betaCpe-containing NPY and PP C-terminal fragments
      encourage the future application of these beta-amino acids in the synthesis of
      selective Y4R ligands. 

PMID- 24090363
TI  - An automatic method for robust and fast cell detection in bright field images
      from high-throughput microscopy.
AB  - BACKGROUND: In recent years, high-throughput microscopy has emerged as a powerful
      tool to analyze cellular dynamics in an unprecedentedly high resolved manner. The
      amount of data that is generated, for example in long-term time-lapse microscopy
      experiments, requires automated methods for processing and analysis. Available
      software frameworks are well suited for high-throughput processing of
      fluorescence images, but they often do not perform well on bright field image
      data that varies considerably between laboratories, setups, and even single
      experiments. RESULTS: In this contribution, we present a fully automated image
      processing pipeline that is able to robustly segment and analyze cells with
      ellipsoid morphology from bright field microscopy in a high-throughput, yet time
      efficient manner. The pipeline comprises two steps: (i) Image acquisition is
      adjusted to obtain optimal bright field image quality for automatic processing.
      (ii) A concatenation of fast performing image processing algorithms robustly
      identifies single cells in each image. We applied the method to a time-lapse
      movie consisting of ~315,000 images of differentiating hematopoietic stem cells
      over 6 days. We evaluated the accuracy of our method by comparing the number of
      identified cells with manual counts. Our method is able to segment images with
      varying cell density and different cell types without parameter adjustment and
      clearly outperforms a standard approach. By computing population doubling times,
      we were able to identify three growth phases in the stem cell population
      throughout the whole movie, and validated our result with cell cycle times from
      single cell tracking. CONCLUSIONS: Our method allows fully automated processing
      and analysis of high-throughput bright field microscopy data. The robustness of
      cell detection and fast computation time will support the analysis of high
      content screening experiments, on-line analysis of time-lapse experiments as well
      as development of methods to automatically track single-cell genealogies.

PMID- 24090365
TI  - Protective effect of Zhuyeqing liquor, a Chinese traditional health liquor, on
      acute alcohol-induced liver injury in mice.
AB  - The study first evaluated the hepatoprotective effect of Zhuyeqing Liquor (ZYQL)
      against acute alcohol-induced liver injury in mice. Animals were administered
      orally with 50% alcohol 12 ml/kg at 4 h after the doses of ZYQL everyday for
      fourteen consecutive days except mice in normal group. The protective effect was
      evaluated by biochemical parameters including serum aspartate transaminase (AST),
      alanine transferase (ALT), total-bilirubin (TBIL) and reduced glutathione (GSH),
      malondialdehyde (MDA), superoxide dismutase (SOD) in liver tissue. The result
      were confirmed histopathologically and the expression of TNF-alpha in mice liver
      was determined by immunohistochemistry analysis. HPLC-PDA was used for
      phytochemical analysis of ZYQL, and the plant source of each compound was
      claritied by UPLC-TOF-MS. The result showed that pretreatment with ZYQL exhibited
      a significant protective effect by reversing the biochemical parameters and
      histopathological changes in a dose depended manner. HPLC analysis indicated that
      ZYQL contained flavonoids, iridoids, terpenoids and phenolic acids, which might
      be the active chemicals. This study demonstrated the hepatoprotective activity of
      ZYQL, thus scientifically supported the function of its health care. 

PMID- 24090367
TI  - Laparoendoscopic single-site surgery using innovative articulating instruments:
      preclinical evaluation of the prototype.
AB  - Conventional articulating instruments for laparoendoscopic single-site (LESS)
      surgery have three major drawbacks: Weak articulating force, internal and
      external crowding, and mirror imaging and motion. The RoboHandTM is a recently
      developed novel articulating instrument. The goal of its development was to
      minimize the abovementioned three major drawbacks. In an ex vivo test, the joint
      force of the RoboHand was 2.5 to 3 times stronger than that of the LaparoAngleTM
      or the SILSTM instrument. In the porcine nephrectomy model, the operative times
      in the RoboHand group (28.8+/-6.6 min) were shorter than those in the LaparoAngle
      group (39.7+/-5.4 min), although not significant (P=0.146). The RoboHand
      prototype seems to be superior to other articulating laparoscopic instruments in
      its mechanical properties, such as joint force, and not to be clinically inferior
      to LaparoAngle for LESS. We describe the techniques for using this innovative
      instrument and discuss its advantages.

PMID- 24090366
TI  - Enhancement of BMP-2 induced bone regeneration by SDF-1alpha mediated stem cell
      recruitment.
AB  - Treatment of critical size bone defects is challenging. Recent studies showed
      that the cytokine stromal cell-derived factor 1 alpha (SDF-1alpha) has potential
      to improve the bone regenerative effect of low bone morphogenetic protein 2 (BMP
      2) concentrations. The goal of this study was to demonstrate the combined effect
      of SDF-1alpha and BMP-2 on bone regeneration and stem cell recruitment using a
      critical size femoral bone defect model. A total of 72 mice were randomized to
      six groups. External fixators were implanted onto the right femur of each mouse
      and 3 mm defects were created. Depending on the group affiliation, adenovirally
      activated fat tissue grafts expressing SDF-1alpha or/and BMP-2 were implanted at
      the defect site. One day after operation, 1*106 murine mesenchymal stromal cells
      (MSCs), lentivirally transduced to express the gene enhanced green fluorescent
      protein (eGFP), firefly luciferase, and CXCR4 were injected systemically in
      selected groups. Migration of the injected MSCs was observed by bioluminescence
      imaging on days 0, 2, 4, 6, 8, 10, 12, 14, 21, 28, and 42. After 6 weeks, animals
      were euthanized and 80 MUm CT-scans were performed. For histological
      investigations, hematoxylin and eosin-, tartrate-resistant acid phosphatase-,
      alkaline phosphatase-, and anti-eGFP-stained sections were prepared. BMP-2 and
      SDF-1alpha combined at the defect site increased bone volume (BV) (2.72 mm3; 95%
      CI 1.95-3.49 mm3) compared with the negative control group (1.80 mm3; 95% CI 1.56
      2.04 mm3; p<0.05). In addition, histological analysis confirmed a higher degree
      of bone healing in the BMP-2 and SDF-1alpha combined group compared with the
      negative control group. Bioluminescence imaging demonstrated higher numbers of
      migrated MSCs toward the defect site in the presence of both BMP-2 and SDF-1alpha
      at the defect site. Furthermore, eGFP-labeled migrated MSCs were found in all
      defect areas, when cells were injected. The ratio of osteoblasts to osteoclasts,
      assessed by immunohistological staining, was higher and thus showed a trend
      toward more bone formation for the combined use of BMP-2 and SDF-1alpha compared
      with all other groups. This study demonstrated that SDF-1alpha enhanced BMP-2
      mediated bone healing in a critical size segmental bone defect model. Notably,
      both proteins alone also provided a cumulative effect on MSC attraction toward
      the site of injury.

PMID- 24090371
TI  - Multicomponent prins cyclization from allylsilyl alcohols leading to
      dioxaspirodecanes.
AB  - A multicomponent reaction for the preparation of dioxaspirodecanes starting from
      allylsilyl alcohols was achieved. The one-pot sequence involves the sequential
      acid-catalyzed reaction of an allylsilyl alcohol with an aldehyde to afford an
      alkenediol. The subsequent Prins cyclization of the homoallylic alcohol moiety
      generates a tetrahydropyranyl carbocation which is intramolecularly trapped by
      the second hydroxyl group. The chemoselectivity of the process shows dependence
      on the nature of the aldehyde and the concentration of the catalyst. 

PMID- 24090370
TI  - A combined community- and facility-based approach to improve pregnancy outcomes
      in low-resource settings: a Global Network cluster randomized trial.
AB  - BACKGROUND: Fetal and neonatal mortality rates in low-income countries are at
      least 10-fold greater than in high-income countries. These differences have been
      related to poor access to and poor quality of obstetric and neonatal care.
      METHODS: This trial tested the hypothesis that teams of health care providers,
      administrators and local residents can address the problem of limited access to
      quality obstetric and neonatal care and lead to a reduction in perinatal
      mortality in intervention compared to control locations. In seven geographic
      areas in five low-income and one middle-income country, most with high perinatal
      mortality rates and substantial numbers of home deliveries, we performed a
      cluster randomized non-masked trial of a package of interventions that included
      community mobilization focusing on birth planning and hospital transport,
      community birth attendant training in problem recognition, and facility staff
      training in the management of obstetric and neonatal emergencies. The primary
      outcome was perinatal mortality at >=28 weeks gestation or birth weight >=1000 g.
      RESULTS: Despite extensive effort in all sites in each of the three intervention
      areas, no differences emerged in the primary or any secondary outcome between the
      intervention and control clusters. In both groups, the mean perinatal mortality
      was 40.1/1,000 births (P = 0.9996). Neither were there differences between the
      two groups in outcomes in the last six months of the project, in the year
      following intervention cessation, nor in the clusters that best implemented the
      intervention. CONCLUSIONS: This cluster randomized comprehensive, large-scale,
      multi-sector intervention did not result in detectable impact on the proposed
      outcomes. While this does not negate the importance of these interventions, we
      expect that achieving improvement in pregnancy outcomes in these settings will
      require substantially more obstetric and neonatal care infrastructure than was
      available at the sites during this trial, and without them provider training and
      community mobilization will not be sufficient. Our results highlight the critical
      importance of evaluating outcomes in randomized trials, as interventions that
      should be effective may not be. TRIAL REGISTRATION: ClinicalTrials.gov
      NCT01073488.

PMID- 24090374
TI  - Di-, tri-, and tetranuclear nickel(II) complexes with oximato bridges: magnetism
      and catecholase-like activity of two tetranuclear complexes possessing rhombic
      topology.
AB  - Oxime-based tridentate Schiff base ligands 3-[2-(diethylamino)ethylimino]butan-2
      one oxime (HL(1)) and 3-[3-(dimethylamino)propylimino]butan-2-one oxime (HL(2))
      produced the dinuclear complex [Ni2L(1)2](ClO4)2 (1) and trinuclear complex
      [Ni3(HL(2))3(MU3-O)](ClO4)4.CH3CN (2), respectively, upon reaction with
      Ni(ClO4)2.6H2O. However, in a slightly alkaline medium, both of the ligands
      underwent hydrolysis and resulted in tetranuclear complexes [{Ni(deen)(H2O)}2(MU3
      OH)2{Ni2(moda)4}](ClO4)2.2CH3CN (3) and [{Ni(dmpn)(CH3CN)2}2(MU3
      OH)2{Ni2(moda)4}](ClO4)2.CH3CN (4), where deen = 2-(diethylamino)ethylamine, dmpn
      = 3-(dimethylamino)-1-propylamine, and modaH = diacetyl monoxime. All four
      complexes have been structurally characterized. Complex 1 is a centrosymmetric
      dimer where the square planar nickel(II) atoms are joined solely by the oximato
      bridges. In complex 2, three square planar nickel atoms form a triangular core
      through a central oxido (MU3-O) and peripheral oximato bridges. Tetranuclear
      complexes 3 and 4 consist of four distorted octahedral nickel(II) ions held
      together in a rhombic chair arrangement by two central MU3-OH and four peripheral
      oximato bridges. Magnetic susceptibility measurements indicated that dinuclear 1
      and trinuclear 2 exhibited diamagnetic behavior, while tetranuclear complexes 3
      and 4 were found to have dominant antiferromagnetic intramolecular coupling with
      concomitant ferromagnetic interactions. Despite its singlet ground state, both 3
      and 4 serve as useful examples of Kahn's model for competing spin interactions.
      High-frequency EPR studies were also attempted, but no signal was detected,
      likely due to the large energy gap between the ground and first excited state.
      Complexes 3 and 4 exhibited excellent catecholase-like activity in the aerial
      oxidation of 3,5-di-tert-butylcatechol to the corresponding o-quinone, whereas 1
      and 2 did not show such catalytic activity. Kinetic data analyses of this
      oxidation reaction in acetonitrile revealed that the catalytic activity of 3
      (kcat = 278.4 h(-1)) was slightly lower than that of 4 (kcat = 300.0 h(-1)). X
      band EPR spectroscopy indicated that the reaction proceeded through the formation
      of iminoxyl-type radicals. 

PMID- 24090372
TI  - Invasive and non-invasive brain stimulation for treatment of neuropathic pain in
      patients with spinal cord injury: a review.
AB  - CONTEXT: Past evidence has shown that invasive and non-invasive brain stimulation
      may be effective for relieving central pain. OBJECTIVE: To perform a topical
      review of the literature on brain neurostimulation techniques in patients with
      chronic neuropathic pain due to traumatic spinal cord injury (SCI) and to assess
      the current evidence for their therapeutic efficacy. METHODS: A MEDLINE search
      was performed using following terms: "Spinal cord injury", "Neuropathic pain",
      "Brain stimulation", "Deep brain stimulation" (DBS), "Motor cortex stimulation"
      (MCS), "Transcranial magnetic stimulation" (TMS), "Transcranial direct current
      stimulation" (tDCS), "Cranial electrotherapy stimulation" (CES). RESULTS:
      Invasive neurostimulation therapies, in particular DBS and epidural MCS, have
      shown promise as treatments for neuropathic and phantom limb pain. However, the
      long-term efficacy of DBS is low, while MCS has a relatively higher potential
      with lesser complications that DBS. Among the non-invasive techniques, there is
      accumulating evidence that repetitive TMS can produce analgesic effects in
      healthy subjects undergoing laboratory-induced pain and in chronic pain
      conditions of various etiologies, at least partially and transiently. Another
      very safe technique of non-invasive brain stimulation - tDCS - applied over the
      sensory-motor cortex has been reported to decrease pain sensation and increase
      pain threshold in healthy subjects. CES has also proved to be effective in
      managing some types of pain, including neuropathic pain in subjects with SCI.
      CONCLUSION: A number of studies have begun to use non-invasive neuromodulatory
      techniques therapeutically to relieve neuropathic pain and phantom phenomena in
      patients with SCI. However, further studies are warranted to corroborate the
      early findings and confirm different targets and stimulation paradigms. The
      utility of these protocols in combination with pharmacological approaches should
      also be explored.

PMID- 24090373
TI  - The assessment and risk stratification of psychological morbidity in critical
      care survivors.
AB  - Along with the ageing population, there is an expanding number of critical care
      survivors in the community. This group is at risk for both physical and
      psychological morbidity following their stay. Factors that predispose patients to
      commonly reported sequelae such as post-traumatic stress disorder, anxiety and
      depression remain incompletely elucidated. A tool to identify and stratify
      survivors at discharge may improve outcomes by allowing early and targeted
      intervention. Looking forward, the identification of aspects of practice
      associated with long-term adverse consequences should allow us to evolve our
      current protocols in a way that provides long-term benefit for patients. 

PMID- 24090376
TI  - Nutritional supplement usage in patients admitted to a spinal cord injury center.
AB  - OBJECTIVES: To (1) assess food intake; (2) establish the prevalence of dietary
      supplement usage and its associated cost (oral nutritional supplements (ONS);
      vitamin and mineral supplements (VMS)) and; (3) identify the characteristics of
      nutritional supplement users among patients admitted to a spinal cord injury
      (SCI) center. STUDY DESIGN: A single center survey. METHODS: Standardized
      questionnaires were used to collect demographic information, food consumption
      over a 24-hour period, and the use of nutritional supplements. Multivariate
      logistic regression was used to determine the characteristics of dietary
      supplement usage and those using them. RESULTS: Seventy-three patients with SCI
      completed and returned the questionnaires (69.5% response rate). From 67
      questionnaires with food intake data, 21 patients (31.3%) consumed three full
      meals a day. Nine of the full 73 patients (12.3%) received artificial nutritional
      support, 14 of 73 (19.1%) received ONS, 34 of 73 (46.5%) received VMS, and 31 of
      73 (42.4%) required assistance in order to eat. The three supplements most often
      prescribed were multivitamins (19.1%), vitamins B (17.8%), and vitamin D (13.6%).
      VMS use was associated with age (years: >60 vs. <= 60: 62.1 vs. 34.1%, P =
      0.019), nutrition risk (Spinal Nutrition Screening Tool (>= 11 vs. <11: 65.7 vs.
      28.9%, P = 0.001), and serum albumin concentration (<35 vs. >= 35 g/l: 59.6 vs.
      16%, P < 0.01). Patients at nutrition risk were found to consume more ONS than
      the lower risk group (28.5 vs. 10.5%, P = 0.05). The expenditures on ONS and VMS
      were higher in the group at greater nutritional risk (L1878.3 vs. L914.3, P =
      0.005). CONCLUSION: The use of nutritional supplements is common in patients with
      SCI, particularly in older adults and patients with poor nutritional state.
      However, the present study identified only small numbers of patients consuming
      all of their hospital meals, which may well contribute to undernutrition risk.
      Given that a high proportion of patients with SCI require assistance to eat, we
      suggest that further efforts focus on the feasibility of providing feeding
      assistants, and on reviewing the nature of the hospital menu.

PMID- 24090375
TI  - Short hairpin RNA gene silencing of prolyl hydroxylase-2 with a minicircle vector
      improves neovascularization of hindlimb ischemia.
AB  - In this study, we target the hypoxia inducible factor-1 alpha (HIF-1-alpha)
      pathway by short hairpin RNA interference therapy targeting prolyl hydroxylase-2
      (shPHD2). We use the minicircle (MC) vector technology as an alternative for
      conventional nonviral plasmid (PL) vectors in order to improve neovascularization
      after unilateral hindlimb ischemia in a murine model. Gene expression and
      transfection efficiency of MC and PL, both in vitro and in vivo, were assessed
      using bioluminescence imaging (BLI) and firefly luciferase (Luc) reporter gene.
      C57Bl6 mice underwent unilateral electrocoagulation of the femoral artery and
      gastrocnemic muscle injection with MC-shPHD2, PL-shPHD2, or phosphate-buffered
      saline (PBS) as control. Blood flow recovery was monitored using laser Doppler
      perfusion imaging, and collaterals were visualized by immunohistochemistry and
      angiography. MC-Luc showed a 4.6-fold higher in vitro BLI signal compared with PL
      Luc. BLI signals in vivo were 4.3*10(5)+/-3.3*10(5) (MC-Luc) versus 0.4*10(5)+/
      0.3*10(5) (PL-Luc) at day 28 (p=0.016). Compared with PL-shPHD2 or PBS, MC-shPHD2
      significantly improved blood flow recovery, up to 50% from day 3 until day 14
      after ischemia induction. MC-shPHD2 significantly increased collateral density
      and capillary density, as monitored by alpha-smooth muscle actin expression and
      CD31(+) expression, respectively. Angiography data confirmed the histological
      findings. Significant downregulation of PHD2 mRNA levels by MC-shPHD2 was
      confirmed by quantitative polymerase chain reaction. Finally, Western blot
      analysis confirmed significantly higher levels of HIF-1-alpha protein by MC
      shPHD2, compared with PL-shPHD2 and PBS. This study provides initial evidence of
      a new potential therapeutic approach for peripheral artery disease. The
      combination of HIF-1-alpha pathway targeting by shPHD2 with the robust nonviral
      MC plasmid improved postischemic neovascularization, making this approach a
      promising potential treatment option for critical limb ischemia.

PMID- 24090377
TI  - Potentially modifiable factors associated with non-adherence to phosphate binder
      use in patients on hemodialysis.
AB  - BACKGROUND: Despite the evidence that phosphate binder (PB) is associated with
      improved outcomes many hemodialysis patients do not adhere to prescribed PB
      regimen. Therefore, barriers to PB adherence should be identified and eliminated.
      The purpose of this study was to evaluate PB adherence among hemodialysis
      patients and to explore potentially modifiable factors associated with low PB
      adherence. METHODS: A cross-sectional study (502 patients) was performed in four
      dialysis units in Salvador, Brazil, using data from the second phase of the
      Prospective Study of the Prognosis of Chronic Hemodialysis Patients (PROHEMO).
      Patients were categorized as adherent or non-adherent to PB based on their
      responses to a semi-structured questionnaire. RESULTS: Non-adherence to PB was
      observed for 65.7% of the patients. After adjustments for numerous covariates,
      cerebrovascular disease (odds ratio (OR), 3.30; 95% confidence interval (CI),
      1.03-10.61), higher PTH (OR per each 300 pg/mL, 1.14; 95% CI, 1.01-1.28), lack of
      comprehension of the appropriate time to use PB (OR, 7.09; 95% CI, 2.10-23.95)
      and stopping PB use after feeling better (OR, 4.54; 95% CI, 1.45-14.25) or
      feeling worse (OR, 11.04; 95% CI, 1.79- 68.03) were significantly associated with
      PB non-adherence. By contrast, the adjusted odds of PB non-adherence were lower
      for patients with more years on dialysis (OR by each 2 years, 0.87; 95% CI, 0.80
      0.95), with serum phosphorus above 5.5 mg/dL (OR, 0.53; 95% CI 0.34-0.82), who
      referred that were encouraged by the dialysis staff to be independent (OR, 0.52;
      95% CI 0.30-0.90), and reported that the nephrologist explained how PB should be
      used (OR, 0.20; 95% CI 0.05-0.73). CONCLUSION: The results of the present study
      are encouraging by showing evidence that improvement in the care provided by the
      dialysis staff and the attending nephrologist may play an important role in
      reducing the high prevalence of non-adherence to PB in maintenance hemodialysis
      patients. A new questionnaire is presented and may help to evaluate
      systematically the patients regarding PB adherence in hemodialysis setting.

PMID- 24090379
TI  - [Influence of intensive hypolipidemic therapy on blood concentration of
      lipoprotein-associated phospholipase A2 in patients with ischemic heart disease].
AB  - AIM: To assess the impact of combined treatment with simvastatin and ezetimibe or
      treatment with simvastatin only on lipoprotein-associated phospholipase A2 in
      patients with ischemic heart disease. METHODS: One hundred patients with
      angiographically documented coronary atherosclerosis took part in the
      investigation. Lp-PLA2 mass and cholesterol fractions were determined at baseline
      and after 6 months of treatment. Lp-PLA2 mass was determined by enzyme
      immunoassay method, using two highly specific monoclonal antibodies. RESULTS:
      Combined treatment with ezetimibe and simvastatin led to significantly greater
      declines in Lp-PLA2 and cholesterol fractions compared with treatment only with
      simvastatin: Lp-PLA2 decreased by 46 vs 38%, total cholesterol by 35 vs 28%, LDL
      cholesterol by 50 vs 40%, respectively (p<0.05). Combination therapy with
      ezetimibe and simvastatin 20 and 40mg/day proved to be as effective as
      monotherapy with simvastatin 80 mg/day on the effect on Lp-PLA2 mass and
      cholesterol fractions (p<0.05). Lp-PLA2 correlated positively with total
      cholesterol (r=0.28) and LDL-C (r=0.33). CONCLUSIONS: Combined treatment led to
      greater reduction of total cholesterol and LDL-C, as well as significantly
      reduced level of Lp-PLA2 mass. The latter can be considered as target for
      suppression of inflammation and achievement of stabilization of atherosclerotic
      plaque.

PMID- 24090378
TI  - Online support for individuals with spinal cord injuries: an ethnographic
      investigation.
AB  - BACKGROUND: Although social support is an important protective factor for
      individuals with spinal cord injuries (SCIs), individuals often encounter
      significant barriers to obtaining support after experiencing a SCI. It has been
      suggested that the Internet may serve to help individuals with disabilities
      overcome common barriers in obtaining support, yet research examining the
      efficacy of Internet-based support for individuals with SCI has been mixed.
      OBJECTIVE: To develop a more nuanced understanding of how individuals with SCI
      can or might use the Internet for support. DESIGN: Using an ethnographic
      approach, we conducted semi-structured interviews with nine individuals with SCI
      to explore perceived needs and barriers to information-seeking and online
      support. SETTING: Participants were recruited from Veterans Administration
      medical center outpatient and inpatient units providing specialty care to
      individuals with SCIs and from a community SCI Center of Excellence. RESULTS:
      Individuals with SCI gain emotional, problem-focused, and reciprocal support from
      online sources. CONCLUSIONS: Online resources can provide important opportunities
      for social support for individuals with SCI.

PMID- 24090380
TI  - [Erythrophagocytosis: a new diagnostic marker of immunologic myocardial damage in
      ischemic heart disease].
AB  - Using data of epidemiological and clinical examination of women of reproductive
      and menopausal age we studied the processes of erythrophagocytosis (EF) in 46
      women with ischemic heart disease (IHD) aged 20-59 years in comparison with a
      group of healthy individuals. We found that women with IHD had almost 10-fold
      increase of EF compared with healthy individuals. Therefore determination of EF
      could be used as laboratory test for detecting autoimmune component of IHD. We
      also found associations between identified immunological abnormalities and
      dyslipidemia, in particular elevation of low density lipoprotein cholesterol
      level which was more pronounced during menopause. EF can serve as an
      immunological marker of IHD in women. 

PMID- 24090381
TI  - [Abnormal glucose tolerance and long-term prognosis in patients with acute
      myocardial infarction].
AB  - STUDY AIM: to assess clinical outcomes and cardiovascular events during long-term
      follow-up after acute myocardial infarction (AMI) in patients (pts) with newly
      detected abnormal glucose tolerance (AGT). MATERIAL AND METHODS: Consecutive AMI
      pts (n=391, 24.3% with diabetes mellitus [DM]) were enrolled in the study. Pts
      with no DM underwent an oral glucose tolerance test (OGTT) at discharge (around
      12-th day). All pts were divided into 3 groups: group I - pts with normal glucose
      tolerance (NGT), group II - pts with AGT, including impaired glucose tolerance
      (IGT) and newly diagnosed DM (NDM), group III - pts with previously known DM.
      General and cardiovascular mortality, adverse cardiovascular events during long
      term follow-up (26.8+/-6 months) were studied. RESULTS: According to the OGTT
      67.9% pts had NGT and 32.1% had AGT (28.7% IGT and 3.4% NDM). Pts with
      disturbances of glucose metabolism were older, had abdominal obesity, more
      frequently had Killip class >2 on admission, as well as reduced ejection
      fraction, left ventricular aneurism and progression of chronic heart failure at
      discharge. Cardiovascular and general mortality during follow-up were
      significantly higher in pts with AGT and DM compared to NGT (27.4 vs. 22.1 vs
      11.1%, p=0.002, and 23.2 vs. 20.2 vs 10.1%, p<0.05, respectively). The incidence
      of recurrent nonfatal MI and stroke were similar in the three groups, however the
      proportion of subjects with heart failure NYHA class >2, revascularization
      procedures, hospitalization due to cardiovascular events was higher in pts with
      abnormalities of carbohydrate metabolism. CONCLUSIONS: Abnormal glucose tolerance
      (IGT and NDM) has high prevalence in AMI patients without known DM, is a major
      risk factor for future cardiovascular events and is associated with unfavorable
      long term prognosis after MI.

PMID- 24090382
TI  - [Association between structure of atherosclerotic plaques in carotid arteries and
      myocardial infarction].
AB  - Aim of this study was to investigate association between structure of
      atherosclerotic plaque (AP) in internal carotid artery and myocardial infarction
      (MI), as well as to elucidate factors which may determine expansion of APs into
      coronary arteries. MATERIAL AND METHODS: We studied 655 patients (148 with MI and
      507 without MI) subjected to carotid artery enderterectomy. Degree of stenosis of
      brachiocephalic arteries (BCA) was proven by angiography. Carotid AP structure
      was assessed by ultrasonography and directly during endarterectomy. The following
      factors were registered: age, sex, fibrinogen level, presence of diabetes,
      hypertension, smoking, hypercholesterolemia, intermittent claudication, and
      atrial fibrillation. RESULTS: Groups with and without MI did not differ
      significantly as regards age, sex, hypercholesterolemia, fibrinogen, diabetes,
      smoking, and degree of carotid artery stenosis. Patients with MI significantly
      more frequently had hypertension (75 vs. 63.9%, p=0.012), other than operated BCA
      stenosis >50% (58.1 vs. 46%, p<0.01), unstable carotid plaque (82 vs. 75.1%,
      p=0.026), carotid plaque hemorrhage (43.2 vs. 17.6%, p=0.001). Logistic
      regression analysis showed that the presence of unstable carotid plaque (odds
      ratio [OR] 2.3, 95% confidence interval [CI] 1.02-5.17, p=0.04) and significant
      stenosis in other BCAs (OR1.81, 95%CI 1-3.26, p=0.049) predicted unstable
      coronary artery disease expressed clinically as myocardial infarction.
      CONCLUSION: BCA AP instability (especially plaque hemorrhage) and presence of
      stenosis >50% in more than one BCA may reflect expansion of unstable APs into
      coronary arteries and development of MI.

PMID- 24090383
TI  - [Role of renal dysfunction and multifocal atherosclerosis in assessment of
      prognosis of patients presenting with ST-elevation acute coronary syndrome].
AB  - AIM: To assess incidence and severity of renal dysfunction as well as its
      prognostic value in patients with ST elevation myocardial infarction (STEMI) and
      multifocal atherosclerosis (MFA). MATERIAL AND METHODS: We enrolled in this study
      529 patients with STEMI in whom we estimated creatinine clearance rate (eGFR) and
      glomerular filtration rate (eCrCl) using Cockcroft-Gault equation and
      Modification of Diet in Renal Disease (MDRD) formula, respectively. Duplex
      ultrasonography of lower extremity and extracranial arteries was performed in 423
      patients on day 5-10 of hospitalization. Signs of MFA were found in 95% of
      patients. Hospital mortality was 10.9%. One year survival of 397 patients was
      assessed by the telephone contacts. Thirty nine patients (9.8%) died. RESULTS:
      GFR in 35.5% of patients was 30-60, and in 4.9% - less than 30 ml/min/1.73 m2. At
      the same time 29.5% of patients had CCr 30 - 60, and 3.0% - less than 30 ml/min.
      Progressive decreases of eCCr and eGFR were observed in patients with incipient
      MFA (stenosis <30%); relationship between MFA and eGRF was more close. Presence
      of renal dysfunction in patients with STEACS and MFA was associated elevation of
      both hospital and 1 year mortality. CONCLUSION: Any manifestation of peripheral
      atherosclerosis and impairment of renal function should be considered as
      independent predictors of cardiovascular events in patients after STEMI.

PMID- 24090384
TI  - [Magnesium orotate in treatment of chronic hypertension in pregnant women].
AB  - We examined 150 pregnant women with essential hypertension (EHT), EHT and
      connective tissue dysplasia (CTD), and healthy. Presence of CTD aggravated
      clinical picture of EHT and was associated with pronounced cardialgic,
      neurological, asthenic, vertebrogenic, visceral, and other syndromes. The use of
      antihypertensive, metabolic (magnesium orotate) drugs, sedative and uroseptic
      phytotherapy, application of other nondrug measures in conditions of
      multidisciplinary dynamic support of the gestational period facilitated regress
      of clinical symptoms of EHT and EHT+CTD, favorable course of pregnancy and
      successful delivery. 

PMID- 24090385
TI  - [Heart rate turbulence and T-wave alternans as markers of risk of sudden cardiac
      death in patients with hypertrophic cardiomyopathy].
AB  - AIM: to study microvolt T-wave alternans (mTWA) and heart rate turbulence (HRT)
      in patients with hypertrophic cardiomyopathy (HCMP). MATERIAL AND METHODS: We
      examined 50 patients with HCMP: 15 (28%) with obstructive form, 23 (46%) with
      major risk factors of sudden cardiac death (SCD), 7 (14%) with left ventricular
      thickness more or equal 3 cm, 6 (12%) with family history of SCD, 16 (32%) with
      attacks of nonsustained ventricular tachycardia (NVT), 5 (10%) with episodes of
      syncope. Control group comparable by age and gender composition comprised 50
      persons without cardiovascular diseases. All patients were subjected to 24-hour
      ECG monitoring with registration of parameters of variability and HRT (turbulence
      onset [TO], turbulence slope), maximal mTWA values, mTWA at heart rate 100 bpm,
      mTWA at 05.00 AM (mTWA05:00). RESULTS: Patients with HCMP compared to controls
      were characterized by significantly higher values of mTWA05:00 (19 [13;30] and 9
      [4;15] mcV, respectively, p<0.001). There was tendency to greater prevalence of
      pathological HRT values in patients with HCMP compared with healthy subjects
      (p=0.083). Prevalence of pathological TO values among patients (16%) was
      significantly higher than among controls (2%), (p<0.05). CONCLUSIONS: Compared to
      healthy subjects patients with HCMP were characterized by higher mTWA05:00 and
      higher prevalence of pathological values of TO. mTWA was directly related to
      numbers of ventricular extrasystoles and NVT attacks. Patients with attacks of
      NVT compared with those without had lower SDNN pNN50.

PMID- 24090386
TI  - [Variability of glycemia and ventricular rhythm disturbances in patients with
      chronic heart failure and type 2 diabetes mellitus].
AB  - Aim of this observational study was assessment of effect of variability of
      glycemia on ventricular ectopic activity in patients with chronic heart failure
      (CHF) and type 2 diabetes mellitus (n=80). According to study protocol 24-hour
      Holter ECG monitoring was carried out at baseline, and after 3 and 6 months.
      Measurements of blood glucose level were made at 8 points during ECG monitoring -
      before and in 2 hours after main meals, before bedtime and at 3 o'clock in the
      morning. In 20 patients continuous combined monitoring of ECG and of blood
      glucose level was carried out. During monitoring of ECG high grade ventricular
      arrhythmias were found in 42 patients (53%). Pronounced variations of blood
      glucose level (mean amplitude of glycemic excursion >5 mmol/L) were associated
      with 2.3 fold increase risk of ventricular arrhythmias (p=0.04). A conclusion was
      made that pronounced 24-hour variations of glucose level in blood was associated
      with elevation of ventricular ectopic activity. High 24-hour variability of
      glycemia appeared to be proarrhythmogenic factor in patients with CHF and
      concomitant diabetes.

PMID- 24090387
TI  - [Histological and ultrastructural characteristics of myocardium in heart
      failure].
AB  - Endomyocardial biopsies performed in patients with various forms of
      cardiomyopathies (CMP) and chronic myocarditis in the presence of heart failure
      identified changes indicative of reduction of functioning cardiomyocytes (CMC) at
      the account of their destruction, dedifferentiation and inefficient hypertrophy".
      Energy apparatus of CMC was represented by large masses of destructed small
      mitochondria. Myofibrils were driven to periphery of CMC and appeared atrophic.
      Products of catabolism (lipofuscin, autophagous vacuoles, protein conglomerates)
      were accumulated in CMC. This led to impairment of CMC main function - to exert
      contraction. Reduction of number of capillary vessels per unit of myocardial
      cross-section area was also found. Discussion of problems of morphogenesis of the
      observed changes and of pathogenetic treatment is presented in the article. 

PMID- 24090388
TI  - [Effect of therapy with bisoprolol in postoperative period on rate of cardiac
      complications of extracardiac surgical interventions].

PMID- 24090389
TI  - [Hybrid revascularization: a combined approach to multivessel coronary artery
      lesions].
AB  - Analysis of effectiveness and feasibility of hybrid approach to multivessel
      coronary artery disease and problems of interaction between cardiac surgeons and
      interventional cardiologists in deciding on the choice of revascularization
      method is performed in the article. Hybrid approach to multivessel disease
      defined as sternal sparing, off-pump, minimally invasive, hand sewn left internal
      mammary - left anterior descending (LAD) arteries by-pass graft with percutaneous
      coronary revascularization of non-LAD lesions to achieve functionally complete
      revascularization is described in detail. Data of multicenter studies and
      clinical recommendations for myocardial revascularization is discussed. 

PMID- 24090390
TI  - [Quality of life of patients after coronary bypass surgery: effect of age and
      personality type D].
AB  - AIM: To study effect of age and presence of personality type D on quality of life
      (QL) of patients in one year after coronary bypass surgery (CBS). MATERIAL AND
      METHODS: Assessment of QL before and after surgery was carried out in 408
      patients. Two groups were formed: patients younger than 60 years (n=233) and
      older than 60 years (n=175). Quality of life and presence of personality type D
      was assessed by questionnaires SF-36 and DS-14, respectively. RESULTS: In a year
      after CBS improvement of physical and psychological components of QL (p<0.05) was
      noted in both groups. Personality type D was more frequent among patients older
      than 60 years (p<0.01). Patients with personality type D had worse parameters of
      irrespective of age (p<0.01). Personality type D correlated directly with age QL
      (p=0.003) and inversely with parameters of QL (p<0.01). Presence of personality
      type D was an independent predictor of low level of physical (together with index
      of atherogenecity prior to surgery) and psychological components of QL at
      multiple logistic regression analysis. CONCLUSION: Assessment of personality
      traits of patients before CBS can be helpful for targeted measures aimed at
      improvement of QL what is especially important for older age groups.

PMID- 24090391
TI  - [The diagnostic efficiency of the methods of separate and combined registration
      of oronasal airflow and pulse oximetry for detection of the obstructive sleep
      apnea/hypopnea syndrome].
AB  - The diagnostic efficiency of the methods of separate and combined registration of
      oronasal airflow and pulse oximetry in order to identify the obstructive sleep
      apnea/hypopnea syndrome (OSAHS) is studied in this work. Patients with
      cardiovascular diseases with complaints on sleep disorders were included in the
      study. Combined registration of oronasal airflow and pulse oximetry during sleep
      were performed for all examined patients (diagnostic system ApneaLink with pulse
      oximetry, ResMed). Registration results of oronasal airflow and pulse oximetry
      were analyzed separately and together. Apnea/hypopnea index (classic,
      recommended), desaturation index with a threshold of desaturation of 4% and 3%
      were evaluated as the diagnostic criteria for the identification of OSAHS. Also,
      in this paper the "apnea/hypopnea combined index" summarizing hypopnea episodes,
      which are associated with significant desaturation and without desaturation, was
      tested. As a method of comparison, polysomnography (Embla N7000, MedCare Flaga),
      which was carried out simultaneously with the main study, was used. The
      diagnostic efficiency of test methods and their criteria assessed by ROC-analysis
      (receiver operator characteristic, the characteristic curve analysis). The
      results of the study showed that combined registration of respiratory oronasal
      airflow and pulse oximetry during sleep was most effectively identified OSAHS and
      can be used as a screening method. The most accurate diagnostic criterion for
      identification of OSAHS is an "apnea/hypopnea combined index". 

PMID- 24090392
TI  - [Cardioprotective effect of remote postconditioning: mechanisms and possibility
      of clinical application].
AB  - Experimental data indicate that postconditioning at distance is an effective
      method of cardiac protection against reperfusion injury. Remote postconditioning
      prevents reperfusion necrosis and apoptosis of cardiomyocytes, decreases
      probability of postinfarction remodeling of the heart. Cardioprotective effect of
      remote postconditioning is depended on release from tissues after transient
      ischemia of humoral factor(s) increasing cardiac tolerance to long-term ischemia
      reperfusion. Clinical studies show that postconditioning at distance is an
      effective method of prevention of reperfusion injury of the heart during coronary
      artery bypass surgery. 

PMID- 24090393
TI  - [Comprehensive organoprotection in patients with high cardiovascular risk: the
      possibility of ramipril from positions of evidence-based medicine].
AB  - Ramipril - a drug with a large evidence base. Various aspects of choosing a drug
      in cardiology from the standpoint of evidence-based medicine are risen from his
      example. 

PMID- 24090394
TI  - Thermoelectric performance of SrTiO3 enhanced by nanostructuring-self-assembled
      particulate film of nanocubes.
AB  - Self-assembled particulate films with a uniform structure over a large area were
      prepared from La-SrTiO3 nanocubes for thermoelectric applications. UV irradiation
      was used to assist the formation of particulate film for decomposition of the
      organic phase in situ to obtain a mechanically robust structure at high
      temperature. The thermoelectric properties of the particulate film were measured
      after calcination at 1000  degrees C under a reductive atmosphere (Ar/H2 =
      60/40). A Seebeck coefficient of S = -239 +/- 24 MUV/K, electrical conductivity
      of sigma = 160 +/- 5 S/cm, and thermal conductivity of kappa ~ 1.5 W/mK were
      obtained for a self-assembled particulate film (La: 5%) corresponding to a ZT
      value of 0.2 at room temperature, which exceeded that of a La-SrTiO3 single
      crystal with similar composition. 

PMID- 24090396
TI  - HIV testing practices as reported by HIV-infected patients in four European
      countries.
AB  - HIV testing constitutes an important strategy to control the HIV epidemic, which
      therefore merits an observation of HIV testing practices to help improve testing
      effectiveness. In 2008, a cross-sectional survey among recently diagnosed (<= 3
      years) HIV-infected patients was conducted in Belgium, Estonia, Finland and
      Portugal. Participants were questioned about reasons for HIV testing, testing
      place and testing conditions. Univariate and multivariate analyses were
      performed. Out of 1460 eligible participants, 629 (43%) were included. Forty-one
      per cent were diagnosed late and 55% had never undergone a previous HIV test with
      perceived low risk being the primary reason for not having been tested earlier.
      Heterogeneity in HIV testing practices was observed across countries. Overall,
      tests were most frequently conducted in primary care (38%) and specialised
      clinics (21%), primarily on the initiative of the health care provider (65%).
      Sixty-one per cent were tested with informed consent, 31% received pretest
      counselling, 78% received post-test counselling, 71% were involved in partner
      notification and 92% were in care three months after diagnosis. The results
      showed that HIV testing is done in a variety of settings suggesting that multiple
      pathways to HIV testing are provided. HIV testing practice is being normalised,
      with less focus on pretest counselling, yet with emphasis on post-test follow-up.
      Major barriers to testing are centred on the denial of risk. Efforts are needed
      to concurrently promote public awareness about HIV risk and benefits of HIV
      testing and train clinicians to be more proactive in offering HIV testing. 

PMID- 24090395
TI  - Patient perceptions regarding benefits of single visit scale and polish: a
      randomised controlled trial.
AB  - BACKGROUND: Single visit scale and polish is frequently carried out in dental
      practices however there is little evidence to support (or refute) its clinical
      effectiveness. The purpose of this research was to compare patient-reported
      outcomes between groups receiving a scale and polish at 6-, 12-, and 24-month
      intervals. Outcomes recorded included participants' subjective assessment of
      their oral cleanliness; the perceived importance of scale and polish for oral
      health and aesthetics; and frequency at which this treatment is required.
      METHODS: A practice-based randomised control trial was undertaken, with a 24
      month follow-up period. Participants were healthy adults with no significant
      periodontal disease (BPE codes <3) randomly allocated to three groups to receive
      scale and polish at 6-, 12-, or 24-month intervals. Patient-reported outcomes
      were recorded at baseline and follow-up. Oral cleanliness was reported using a 5
      point scale and recorded by examiners blinded to trial group allocation. A self
      completed questionnaire enabled participants to report perceived importance of
      scale and polish (5-point scale), and required frequency of treatment (6-point
      scale). The main hypothesis was that participants receiving 6-monthly scale and
      polish would report higher levels of oral cleanliness compared to participants
      receiving scale and polish at 12- and 24-month intervals. RESULTS: 369
      participants were randomised: 125 to the 6-month group; 122 to the 12-month
      group; and 122 to the 24-month group. Complete data set analysis was carried out
      to include 107 (6-month group), 100 (12-month group) and 100 (24-month group)
      participants. Multiple imputation analyses were conducted where follow-up data
      was missing. The difference in the proportions of participants reporting a 'high'
      level of oral cleanliness at follow-up was significant (Chi-squared P = 0.003):
      52.3% (6-month group), 47.0% (12-month group) and 30.0% (24-month group). Scale
      and polish was thought to be important by the majority in each group for keeping
      mouths clean and gums healthy, whitening teeth, and preventing bad breath and
      tooth decay; there were no statistically significant differences between groups
      at follow-up. Most participants at follow-up thought that the frequency of scale
      and polish should be "every 6 months" or more frequently: 77.9% (6-month group),
      64.6% (12-month group), 71.7% (24-month group); differences between groups were
      not statistically significant (Chi squared P = 0.126). The results suggest that
      participants in the 24-month trial group were more likely to choose a scale and
      polish interval of "once a year" or less frequently (OR 2.89; 95% CI 1.36, 6.13).
      CONCLUSIONS: The majority of healthy adults regarded 6-monthly single-visit scale
      and polish as being beneficial for their oral health. Receiving the treatment at
      different frequencies did not alter this belief; and those with the longest
      interval between scale and polish provision perceived that their mouth was less
      clean. In the absence of a strong evidence base to support (or refute) the
      effectiveness of single-visit scale and polish, the beliefs and preferences of
      patients regarding scale and polish may be influential drivers for maintaining
      provision of this treatment.

PMID- 24090397
TI  - Nanoparticle-enhanced laser-induced breakdown spectroscopy of metallic samples.
AB  - In this article, an increase of 1-2 orders of magnitude in laser-induced
      breakdown spectroscopy (LIBS) signals was obtained by depositing silver
      nanoparticles on metal samples. Nanoparticle-enhanced LIBS (NELIBS) was found to
      be a robust and flexible tool for the chemical analysis of metals because the
      sample emission signal did not appear to be affected much by the size and
      concentration of deposited nanoparticles (NPs) within the ranges of 10 nm for
      diameter and 1 order of magnitude for concentration. On the other hand,
      preliminary NELIBS tests on insulators and semiconductors did not show any
      significant enhancement with respect to conventional LIBS. In this article, we
      present a detailed investigation of the fundamental features of NELIBS spectra,
      in addition to some examples of analytical applications to the quantitative
      analysis of metal alloys. 

PMID- 24090398
TI  - A WAO - ARIA - GA2LEN consensus document on molecular-based allergy diagnostics.
AB  - Molecular-based allergy (MA) diagnostics is an approach used to map the allergen
      sensitization of a patient at a molecular level, using purified natural or
      recombinant allergenic molecules (allergen components) instead of allergen
      extracts. Since its introduction, MA diagnostics has increasingly entered routine
      care, with currently more than 130 allergenic molecules commercially available
      for in vitro specific IgE (sIgE) testing.MA diagnostics allows for an increased
      accuracy in allergy diagnosis and prognosis and plays an important role in three
      key aspects of allergy diagnosis: (1) resolving genuine versus cross-reactive
      sensitization in poly-sensitized patients, thereby improving the understanding of
      triggering allergens; (2) assessing, in selected cases, the risk of severe,
      systemic versus mild, local reactions in food allergy, thereby reducing
      unnecessary anxiety for the patient and the need for food challenge testing; and
      (3) identifying patients and triggering allergens for specific immunotherapy
      (SIT).Singleplex and multiplex measurement platforms are available for MA
      diagnostics. The Immuno-Solid phase Allergen Chip (ISAC) is the most
      comprehensive platform currently available, which involves a biochip technology
      to measure sIgE antibodies against more than one hundred allergenic molecules in
      a single assay. As the field of MA diagnostics advances, future work needs to
      focus on large-scale, population-based studies involving practical applications,
      elucidation and expansion of additional allergenic molecules, and support for
      appropriate test interpretation. With the rapidly expanding evidence-base for MA
      diagnosis, there is a need for allergists to keep abreast of the latest
      information. The aim of this consensus document is to provide a practical guide
      for the indications, determination, and interpretation of MA diagnostics for
      clinicians trained in allergology. 

PMID- 24090399
TI  - Quantitative proteomics reveals regulatory differences in the chondrocyte
      secretome from human medial and lateral femoral condyles in osteoarthritic
      patients.
AB  - BACKGROUND: Osteoarthritis (OA) is a destructive joint disease and there are no
      known biomarkers available for an early diagnosis. To identify potential disease
      biomarkers and gain further insight into the disease mechanisms of OA we applied
      quantitative proteomics with SILAC technology on the secretomes from chondrocytes
      of OA knees, designated as high Mankin (HM) scored secretome. A quantitative
      comparison was made between the secretomes of the medial and lateral femur
      condyle chondrocytes in the same knee since the medial femur condyle is usually
      more affected in OA than the lateral condyle, which was confirmed by Mankin
      scoring. The medial/lateral comparison was also made on the secretomes from
      chondrocytes taken from one individual with no clinically apparent joint-disease,
      designated as low Mankin (LM) scored secretome. RESULTS: We identified 825
      proteins in the HM secretome and 69 of these showed differential expression when
      comparing the medial and lateral femoral compartment. The LM scored femoral
      condyle showed early signs of OA in the medial compartment as assessed by Mankin
      score. We here report the identification and relative quantification of several
      proteins of interest for the OA disease mechanism e.g. CYTL1, DMD and STAB1
      together with putative early disease markers e.g. TIMP1, PPP2CA and B2M.
      CONCLUSIONS: The present study reveals differences in protein abundance between
      medial/lateral femur condyles in OA patients. These regulatory differences expand
      the knowledge regarding OA disease markers and mechanisms.

PMID- 24090401
TI  - p-Type InN nanowires.
AB  - In this Letter, we demonstrate that with the merit of nanowire structure and a
      self-catalytic growth process p-type InN can be realized for the first time by
      "direct" magnesium (Mg) doping. The presence of Mg acceptor energy levels in InN
      is confirmed by photoluminescence experiments, and a direct evidence of p-type
      conduction is demonstrated unambiguously by studying the transfer characteristics
      of InN nanowire field effect transistors. Moreover, the near-surface Fermi-level
      of InN can be tuned from nearly intrinsic to p-type degenerate by controlling Mg
      dopant incorporation, which is in contrast to the commonly observed electron
      accumulation on the grown surfaces of Mg-doped InN films. First-principle
      calculation using the VASP electronic package further shows that the p-type
      surface formed on Mg-doped InN nanowires is highly stable energetically. 

PMID- 24090402
TI  - Ultrafast saturable absorption of two-dimensional MoS2 nanosheets.
AB  - Employing high-yield production of layered materials by liquid-phase exfoliation,
      molybdenum disulfide (MoS2) dispersions with large populations of single and few
      layers were prepared. Electron microscopy verified the high quality of the two
      dimensional MoS2 nanostructures. Atomic force microscopy analysis revealed that
      ~39% of the MoS2 flakes had thicknesses of less than 5 nm. Linewidth and
      frequency difference of the E(1)2g and A1g Raman modes confirmed the effective
      reduction of flake thicknesses from the bulk MoS2 to the dispersions. Ultrafast
      nonlinear optical (NLO) properties were investigated using an open-aperture Z
      scan technique. All experiments were performed using 100 fs pulses at 800 nm from
      a mode-locked Ti:sapphire laser. The MoS2 nanosheets exhibited significant
      saturable absorption (SA) for the femtosecond pulses, resulting in the third
      order NLO susceptibility Imchi((3)) ~ 10(-15) esu, figure of merit ~10(-15) esu
      cm, and free-carrier absorption cross section ~10(-17) cm(2). Induced free
      carrier density and the relaxation time were estimated to be ~10(16) cm(-3) and
      ~30 fs, respectively. At the same excitation condition, the MoS2 dispersions show
      better SA response than the graphene dispersions.

PMID- 24090403
TI  - Efficient and accurate whole genome assembly and methylome profiling of E. coli.
AB  - BACKGROUND: With the price of next generation sequencing steadily decreasing,
      bacterial genome assembly is now accessible to a wide range of researchers. It is
      therefore necessary to understand the best methods for generating a genome
      assembly, specifically, which combination of sequencing and bioinformatics
      strategies result in the most accurate assemblies. Here, we sequence three E.
      coli strains on the Illumina MiSeq, Life Technologies Ion Torrent PGM, and
      Pacific Biosciences RS. We then perform genome assemblies on all three datasets
      alone or in combination to determine the best methods for the assembly of
      bacterial genomes. RESULTS: Three E. coli strains - BL21(DE3), Bal225, and
      DH5alpha - were sequenced to a depth of 100* on the MiSeq and Ion Torrent
      machines and to at least 125* on the PacBio RS. Four assembly methods were
      examined and compared. The previously published BL21(DE3) genome
      [GenBank:AM946981.2], allowed us to evaluate the accuracy of each of the
      BL21(DE3) assemblies. BL21(DE3) PacBio-only assemblies resulted in a 90%
      reduction in contigs versus short read only assemblies, while N50 numbers
      increased by over 7-fold. Strikingly, the number of SNPs in PacBio-only
      assemblies were less than half that seen with short read assemblies (~20 SNPs vs.
      ~50 SNPs) and indels also saw dramatic reductions (~2 indel >5 bp in PacBio-only
      assemblies vs. ~12 for short-read only assemblies). Assemblies that used a
      mixture of PacBio and short read data generally fell in between these two
      extremes. Use of PacBio sequencing reads also allowed us to call covalent base
      modifications for the three strains. Each of the strains used here had a known
      covalent base modification genotype, which was confirmed by PacBio sequencing.
      CONCLUSION: Using data generated solely from the Pacific Biosciences RS, we were
      able to generate the most complete and accurate de novo assemblies of E. coli
      strains. We found that the addition of other sequencing technology data offered
      no improvements over use of PacBio data alone. In addition, the sequencing data
      from the PacBio RS allowed for sensitive and specific calling of covalent base
      modifications.

PMID- 24090404
TI  - Scope and limitations of auxiliary-assisted, palladium-catalyzed arylation and
      alkylation of sp2 and sp3 C-H bonds.
AB  - The scope of palladium-catalyzed, auxiliary-assisted direct arylation and
      alkylation of sp(2) and sp(3) C-H bonds of amine and carboxylic acid derivatives
      has been investigated. The method employs a palladium acetate catalyst,
      substrate, aryl, alkyl, benzyl, or allyl halide, and inorganic base in tert-amyl
      alcohol or water solvent at 100-140  degrees C. Aryl and alkyl iodides as well as
      benzyl and allyl bromides are competent reagents in this transformation. The
      picolinic acid auxiliary is used for amine gamma-functionalization, and the 8
      aminoquinoline auxiliary is used for carboxylic acid beta-functionalization. Some
      optimization of base, additives, and solvent is required for achieving best
      results. 

PMID- 24090405
TI  - Enantioselective synthesis of angularly substituted 1-azabicylic rings: coupled
      dynamic kinetic epimerization and chirality transfer.
AB  - A new strategy for enantioselective synthesis of azacyclic molecules in which
      dynamic kinetic equilibration of diastereomeric iminium ions precedes a
      stereochemistry-determining sigmatropic rearrangement is reported. The method is
      illustrated by the synthesis, in high enantiomeric purity (generally 95-99% ee),
      of a variety of 1-azabicyclic molecules containing angular allyl or 3-substituted
      2-propenyl side chains adjacent to nitrogen and up to three stereogenic centers.
      In these products, the size of the carbocyclic ring is varied widely (5-12
      membered); however, useful yields are obtained in forming 1-azabicyclic products
      containing only fused pyrrolidine and piperidine rings. Chirality transfer from
      substituents at carbons 1 and 2 of the 3-butenylamine fragment of the starting
      material is investigated, with methyl and phenyl substituents at the allylic
      position shown to provide exquisite stereocontrol (generally 98-99% chirality
      transfer). An attractive feature of the method is the ability to carry out the
      key transformation in the absence of solvent. Illustrated also is the high
      yielding conversion of four such products to a new family of bicyclic beta-amino
      acids of high enantiomeric purity. 

PMID- 24090406
TI  - Crystal structure and solution species of Ce(III) and Ce(IV) formates: from
      mononuclear to hexanuclear complexes.
AB  - Cerium(III) and cerium(IV) both form formate complexes. However, their species in
      aqueous solution and the solid-state structures are surprisingly different. The
      species in aqueous solutions were investigated with Ce K-edge EXAFS spectroscopy.
      Ce(III) formate shows only mononuclear complexes, which is in agreement with the
      predicted mononuclear species of Ce(HCOO)(2+) and Ce(HCOO)2(+). In contrast,
      Ce(IV) formate forms in aqueous solution a stable hexanuclear complex of [Ce6(MU3
      O)4(MU3-OH)4(HCOO)x(NO3)y](12-x-y). The structural differences reflect the
      different influence of hydrolysis, which is weak for Ce(III) and strong for
      Ce(IV). Hydrolysis of Ce(IV) ions causes initial polymerization while
      complexation through HCOO(-) results in 12 chelate rings stabilizing the
      hexanuclear Ce(IV) complex. Crystals were grown from the above-mentioned
      solutions. Two crystal structures of Ce(IV) formate were determined. Both form a
      hexanuclear complex with a [Ce6(MU3-O)4(MU3-OH)4](12+) core in aqueous HNO3/HCOOH
      solution. The pH titration with NaOH resulted in a structure with the composition
      [Ce6(MU3-O)4(MU3-OH)4(HCOO)10(NO3)2(H2O)3].(H2O)9.5, while the pH adjustment with
      NH3 resulted in [Ce6(MU3-O)4(MU3-OH)4(HCOO)10(NO3)4].(NO3)3(NH4)5(H2O)5.
      Furthermore, the crystal structure of Ce(III) formate, Ce(HCOO)3, was determined.
      The coordination polyhedron is a tricapped trigonal prism which is formed
      exclusively by nine HCOO(-) ligands. The hexanuclear Ce(IV) formate species from
      aqueous solution is widely preserved in the crystal structure, whereas the
      mononuclear solution species of Ce(III) formate undergoes a polymerization during
      the crystallization process. 

PMID- 24090407
TI  - The Shock Index: is it ready for primetime?
AB  - The rapid and accurate prediction of the need for massive transfusion in bleeding
      trauma patients remains a challenge. Various models have been proposed to
      anticipate massive transfusion with variable success. The current study by
      Mutschler and colleagues proposes four classes of shock as defined by the Shock
      Index and examines its ability to predict the need for massive transfusion. This
      model demonstrates promise as a practical tool in acute decision-making for
      transfusion after injury. 

PMID- 24090409
TI  - Structural and thermodynamic dissection of linear motif recognition by the E.
      coli sliding clamp.
AB  - Protein-protein interactions based on linear motif (LM) recognition play roles in
      many cell regulatory processes. The E. coli sliding clamp is a protein mediator
      of replisome formation, which uses a common surface pocket composed of two
      subsites (I and II) to interact with LMs in multiple binding partners. A
      structural and thermodynamic dissection of sliding clamp-LM recognition has been
      performed, providing support for a sequential binding model. According to the
      model, a hydrophobic C-terminal LM dipeptide submotif acts as an anchor to
      establish initial contacts within subsite I, and this is followed by formation of
      a stabilizing hydrogen-bonding network between the flanking LM residues and
      subsite II. Differential solvation/desolvation during positioning of the
      submotifs is proposed as a driver for the sequential binding. Our model provides
      general insights into linear motif recognition and should guide the design of
      small-molecule inhibitors of the E. coli sliding clamp, an emerging antibacterial
      target. 

PMID- 24090408
TI  - Mitochondrial impairment in the five-sixth nephrectomy model of chronic renal
      failure: proteomic approach.
AB  - BACKGROUND: Kidney injuries provoke considerable adjustment of renal physiology,
      metabolism, and architecture to nephron loss. Despite remarkable regenerative
      capacity of the renal tissue, these adaptations often lead to tubular atrophy,
      interstial and glomerular scaring, and development of chronic kidney disease. The
      therapeutic strategies for prevention of the transition from acute kidney damage
      to a chronic condition are limited. The purpose of this study was to elucidate
      large-scale alterations of the renal cortex proteome in partially nephrecromized
      rats at an early stage of chronic kidney disease. METHODS: Sprague-Dawley 5/6
      nephrectomized rats and sham-operated controls were sacrificed at day 28 post
      surgery. To identify proteins with notable alteration of expression we applied a
      2D-proteomics approach followed by mass-spectrometry. Altered expression of
      identified and related proteins was validated by Western blotting and
      immunohistochemistry. RESULTS: Proteins with increased levels of expression after
      partial nephrectomy were albumin and vimentin. Proteins with decreased expression
      were metabolic or mitochondrial. Western blotting analysis showed that the renal
      cortex of nephrectomized rats expressed decreased amount (by ~50%) of proteins
      from the inner mitochondrial compartment - the beta-oxidation enzyme MCAD, the
      structural protein GRP-75, and the oxidative phosphorylation protein COXIV.
      Mitochondrial DNA copy number was decreased by 30% in the cortex of PNx rats. In
      contrast, the levels of an outer mitochondrial membrane protein, VDAC1, remained
      unchanged in remnant kidneys. Mitochondrial biogenesis was not altered after
      renal mass ablation as was indicated by unchanged levels of PPARgamma and
      PGC1alpha proteins. Autophagy related protein Beclin 1 was up-regulated in
      remnant kidneys, however the level of LC3-II protein was unchanged. BNIP3
      protein, which can initiate both mitochondrial autophagy and cell death, was up
      regulated considerably in kidneys of nephrecomized rats. CONCLUSIONS: The results
      of the study demonstrated that notable alterations in the renal cortex of 5/6
      nephrectomized rats were associated with mitochondrial damage, however
      mitochondrial biogenesis and autophagy for replacement of damaged mitochondria
      were not stimulated. Accumulation of dysfunctional mitochondria after 5/6
      nephrectomy may cause multiple adjustments in biosynthetic pathways, energy
      production, ROS signaling, and activation of pro-cell death regulatory pathways
      thus contributing to the development of chronic kidney disease.

PMID- 24090410
TI  - Nitrosporeusines A and B, unprecedented thioester-bearing alkaloids from the
      Arctic Streptomyces nitrosporeus.
AB  - Chemical examination of an arctic actinomycete Streptomyces nitrosporeus resulted
      in the isolation of two new alkaloids named nitrosporeusines A (1) and B (2), an
      unprecedented skeleton containing benzenecarbothioc cyclopenta[c]pyrrole-1,3
      dione. Their structures were determined through extensive spectroscopic analyses
      in association with X-ray single crystal diffraction. Both 1 and 2 exhibited
      inhibitory activities against the H1N1 virus in MDCK cells. 

PMID- 24090411
TI  - Stenting eyes: the pressure to perform.

PMID- 24090412
TI  - Caught between a rock and a hard place: what is the optimal timing for infantile
      cataract surgery?

PMID- 24090414
TI  - On the photophysics of carotenoids: a multireference DFT study of peridinin.
AB  - We present a quantum-mechanical investigation of the photophysics of a specific
      carotenoid, peridinin, which is present in light-harvesting complexes. The
      fundamental role played by the geometry in determining the position and character
      of its low-lying singlet electronic states is investigated using a multireference
      DFT approach in combination with a continuum solvation model. The main
      photophysical properties of peridinin appear to be governed by the lowest two
      singlet excited states, as no evidence points to an intermediate S* state and the
      energies of the upper excited states are too high to allow their population with
      excitation in the visible range. These two excited states (S1, 2(1)A(g)(-) and
      S2, 1(1)B(u)(+)) are highly connected through the conjugation path here
      characterized by the value of the bond length alternation (BLA). The S1 and S2
      states present distinct natures for small BLA values, whereas for larger ones
      they become more similar in terms of both brightness and dipolar character and
      their energies become closer. The geometrical issue is thus of fundamental
      importance for a correct interpretation of the spectroscopic signatures of
      peridinin.

PMID- 24090415
TI  - Inflammatory demyelination induces glia alterations and ganglion cell loss in the
      retina of an experimental autoimmune encephalomyelitis model.
AB  - BACKGROUND: Multiple sclerosis (MS) is often accompanied by optic nerve
      inflammation. And some patients experience permanent vision loss. We examined if
      the grade of optic nerve infiltration and demyelination affects the severity of
      clinical signs in an experimental autoimmune encephalomyelitis (EAE) model. The
      loss of retinal ganglion cells (RGC) and alterations in glia activity were also
      investigated. METHODS: C57BL/6 mice were immunized with peptide MOG35-55 in
      complete Freund's adjuvant (CFA) and controls received PBS in CFA. Then 23 days
      post immunization eyes were prepared for flatmounts and stained with Nissl to
      evaluated neuronal density. Clinical EAE symptoms as well as cell infiltration
      and demyelination in the optic nerve were examined. Retinal sections were stained
      with hematoxylin and eosin and silver stain. Immunohistochemistry was used to
      label RGCs (Brn-3a), apoptotic cells (caspase 3), macroglia (glial fibrillary
      acidic protein (GFAP)), microglia (Iba1), macrophages (F 4/80) and interleukin-6
      (IL-6) secretion. RESULTS: EAE symptoms started at day 8 and peaked at day 15.
      Cell infiltrations (P = 0.0047) and demyelination (P = 0.0018) of EAE nerves
      correlated with the clinical score (r > 0.8). EAE led to a significant loss of
      RGCs (P< 0.0001). Significantly more caspase 3+ cells were noted in these animals
      (P = 0.0222). They showed an increased expression of GFAP (P< 0.0002) and a
      higher number of microglial cells (P< 0.0001). Also more macrophages and IL-6
      secretion were observed in EAE mice. CONCLUSIONS: MOG immunization leads to optic
      neuritis and RGC loss. EAE severity is related to the severity of optic nerve
      inflammation and demyelination. EAE not only affects activation of apoptotic
      signals, but also causes a glial response in the retina.

PMID- 24090416
TI  - Fibrotic remodeling of tissue-engineered skin with deep dermal fibroblasts is
      reduced by keratinocytes.
AB  - Two-thirds of burn patients with deep dermal injuries are affected by
      hypertrophic scars, and currently, there are no clinically effective therapies.
      Tissue-engineered skin is a very promising model for the elucidation of the role
      of matrix microenvironment and biomechanical characteristics and could help in
      the identification of new therapeutic targets for hypertrophic scars.
      Conventionally, tissue-engineered skin is made of heterogeneous dermal
      fibroblasts and keratinocytes; however, recent work has shown that superficial
      and deep dermal fibroblasts are antifibrotic and profibrotic, respectively.
      Furthermore, keratinocytes are believed to regulate the development and
      remodeling of fibrosis in skin. This study aimed to assess the influence of
      keratinocytes and layered fibroblasts on the characteristics of tissue-engineered
      skin. Layered fibroblasts and keratinocytes isolated from superficial and deep
      dermis and epidermis, respectively, of the lower abdominal tissue were
      independently co-cultured on collagen-glycosaminoglycan scaffolds, and the
      resulting tissue-engineered skin was assessed for differences in tissue
      remodeling based on the underlying specific dermal fibroblast subpopulation.
      Collagen production by deep fibroblasts but not by superficial fibroblasts was
      significantly reduced upon co-culture with keratinocytes. Also, keratinocytes in
      the tissue-engineered skin resulted in significantly reduced expression of
      profibrotic connective tissue growth factor and fibronectin, and increased
      expression of the antifibrotic matrix metalloproteinase-1 by deep fibroblasts but
      not by superficial fibroblasts. Tissue-engineered skin made of deep fibroblasts
      and keratinocytes had lower levels of small proteoglycans, decorin, and
      fibromodulin, and higher levels of large proteoglycan, versican, compared to
      tissue-engineered skin made of superficial fibroblasts and keratinocytes. Tissue
      engineered skin made of deep fibroblasts and keratinocytes had lower expression
      of transforming growth factor (TGF)-alpha, interleukin (IL)-1, and keratinocyte
      growth factor but higher expression of platelet-derived growth factor and IL-6,
      compared to tissue-engineered skin made of superficial fibroblasts and
      keratinocytes. Furthermore, co-culture with keratinocytes reduced TGF-beta1
      production of deep but not superficial fibroblasts. Additionally, keratinocytes
      reduced the differentiation of deep fibroblasts to myofibroblasts in tissue
      engineered skin constructs, but not that of superficial fibroblasts. Taken
      together, keratinocytes reduce fibrotic remodeling of the scaffolds by deep
      dermal fibroblasts. Our results therefore demonstrate that tissue-engineered skin
      made specifically with a homogeneous population of superficial fibroblasts and
      keratinocytes is less fibrotic than that with a heterogeneous population of
      fibroblasts and keratinocytes. 

PMID- 24090417
TI  - HLA-universal platelet transfusions prevent platelet refractoriness in a mouse
      model.
AB  - Refractoriness to platelet (PLT) transfusion caused by alloimmunization against
      HLA class I antigens constitutes a significant clinical problem. Thus, it would
      be desirable to have PLT units lacking HLA antigens on the cell surface.
      Previously, we showed that the generation of functional HLA class I-silenced (HLA
      universal) PLTs from CD34(+) cells, using a short hairpin RNA (shRNA) to target
      beta2-microglobulin (beta2m) transcripts, is feasible. Here, we assessed the
      capacity of HLA-silenced PLTs to escape HLA antibody-mediated cytotoxicity in
      vitro and in vivo. Generation of megakaryocytes (MKs) and PLTs was performed by
      thrombopoietin-mediated differentiation of HLA-silenced CD34(+) cells within 10
      days. Lymphocytotoxicity and antibody-dependent cellular cytotoxicity (ADCC)
      reporter assays using anti-HLA antibodies and a mouse model for PLT
      refractoriness were used to assess the immune-evasion capability of HLA-universal
      MKs and PLTs. To mimic PLT refractoriness in vivo, NOD/SCID/IL-2Rgammac(-/-) mice
      were injected with specific anti-HLA antibodies followed by the infusion of 1 *
      10(6) HLA-universal MKs. In vivo PLT generation was evaluated by flow cytometry
      using anti-CD42a and CD61 antibodies. Cells expressing a nonspecific shRNA were
      used as control. Lymphocytotoxicity and ADCC reporter assays showed that HLA
      silencing protects MKs against HLA antibody-mediated complement-dependent and
      cell-mediated cytotoxicity. In lymphocytotoxicity assays, 80-90% of HLA
      expressing MKs but only 3% of HLA-silenced MKs were lysed. In the circulation of
      mice, HLA-expressing and HLA-silenced MKs showed PLT production in the absence of
      anti-HLA antibodies, with human PLT frequencies of up to 0.5% within the PLT
      population. However, in presence of anti-HLA antibodies HLA-expressing MKs were
      rapidly cleared from the circulation of mice, whereas HLA-silenced MKs escaped
      HLA antibody-mediated cytotoxicity and produced PLTs that were detectable up to
      11 days. Our data show that HLA-silenced PLTs are efficiently protected against
      HLA antibody-mediated cytotoxicity and prevent PLT refractoriness in vivo.
      Provision of HLA-silenced PLTs may become an important component in the
      management of patients refractory to PLT transfusion.

PMID- 24090419
TI  - A systematic quantitative approach to rational drug design and discovery of novel
      human carbonic anhydrase IX inhibitors.
AB  - Drug design involves the design of small molecules that are complementary in
      shape and charge to the biomolecular target with which they interact and
      therefore will bind to it. Three-dimensional quantitative structure-activity
      relationship (3D-QSAR) studies were performed for a series of carbonic anhydrase
      IX inhibitors using comparative molecular field analysis (CoMFA) and comparative
      molecular similarity indices analysis (CoMSIA) techniques with the help of SYBYL
      7.1 software. The large set of 36 different aromatic/heterocyclic sulfamates
      carbonic anhydrase (CA, EC 4.2.1.1) inhibitors, such as hCA IX, was chosen for
      this study. The conventional ligand-based 3D-QSAR studies were performed based on
      the low energy conformations employing database alignment rule. The ligand-based
      model gave q(2) values 0.802 and 0.829 and r(2) values 1.000 and 0.994 for CoMFA
      and CoMSIA, respectively, and the predictive ability of the model was validated.
      The predicted r(2) values are 0.999 and 0.502 for CoMFA and CoMSIA, respectively.
      SEA (steric, electrostatic, hydrogen bond acceptor) of CoMSIA has the significant
      contribution for the model development. The docking of inhibitors into hCA IX
      active site using Glide XP (Schrodinger) software revealed the vital interactions
      and binding conformation of the inhibitors. The CoMFA and CoMSIA field contour
      maps are well in agreement with the structural characteristics of the binding
      pocket of hCA IX active site, which suggests that the information rendered by 3D
      QSAR models and the docking interactions can provide guidelines for the
      development of improved hCA IX inhibitors as leads for various types of
      metastatic cancers including those of cervical, renal, breast and head and neck
      origin.

PMID- 24090418
TI  - Life-threatening outcomes associated with autonomic dysreflexia: a clinical
      review.
AB  - Context Autonomic dysreflexia (AD) is a life-threatening complication of chronic
      traumatic spinal cord injury (SCI). Objective To document and provide insight
      into the life-threatening sequelae associated with AD. Methods A review was
      conducted to identify literature which documented cases of AD associated with
      life-threatening outcomes (and death). The search strategy comprised of a keyword
      search on the PubMed database as well as manual searches of retrieved articles.
      Outcomes were categorized into three main classes: central nervous system (CNS),
      cardiovascular (CV), and pulmonary. Results Thirty-two cases of death or life
      threatening complications of AD were found. Twenty-three (72%) cases were CNS
      related, seven (22%) cases were CV-related, and two (6%) cases were pulmonary
      related. In total, seven (22%) deaths were noted as a direct result of
      complications following an AD attack. Conclusion AD is a well-known consequence
      of SCI among individuals with high thoracic and cervical injuries. Many of these
      individuals experience this condition on a daily basis. Medical personnel, care
      givers, and individuals with SCI should be aware of the importance of timely
      diagnosis and management of this life-threatening condition, which can result in
      a variety of significant complications including stroke, seizures, myocardial
      ischemia, and death. 

PMID- 24090420
TI  - Quantitative insights towards the design of potent deazaxanthine antagonists of
      adenosine 2B receptors.
AB  - Adenosine receptors have been considered as potential targets for drug
      development, but one of the main obstacles to this goal is to selectively inhibit
      one receptor subtype over the others. This subject is particularly crucial for
      adenosine A2b receptor antagonists (AdoRA2B). The structure-activity
      relationships of xanthine derivatives which are AdoRA2B have been comprehensively
      investigated, but the steric and electronic requirements of deazaxanthine AdoRA2B
      have not been described from a quantitative standpoint of view. Herein we report
      our efforts to shorten this knowledge gap through 2D-QSAR (HQSAR) and 3D-QSAR
      (CoMFA) approaches. The good statistical quality (HQSAR--r(2) = 0.85, q(2)(LOO) =
      0.77; CoMFA - r(2) = 0.86, q(2) = 0.70) and predictive ability (r(2) = (pred1) =
      0.78, r(2)(pred2) = 0.78 and r(2) = (pred1) = 0.70, r(2) = (pred2) =
      0.70,respectively) of the models, along with the information provided by
      contribution and contour maps hints their usefulness to the design of more potent
      9-deazaxanthine derivatives.

PMID- 24090421
TI  - Biochemical characterization of Acacia schweinfurthii serine proteinase
      inhibitor.
AB  - One of the many control mechanisms of serine proteinases is their specific
      inhibition by protein proteinase inhibitors. An extract of Acacia schweinfurthii
      was screened for potential serine proteinase inhibition. It was successfully
      purified to homogeneity by precipitating with 80% (v/v) acetone and sequential
      chromatographic steps, including ion-exchange, affinity purification and reversed
      phase high performance liquid chromatography. Reducing sodium dodecyl sulphate
      polyacrylamide gel electrophoresis conditions revealed an inhibitor (ASTI)
      consisting of two polypeptide chains A and B of approximate molecular weights of
      16 and 10 kDa, respectively, and under non-reducing conditions, 26 kDa was
      observed. The inhibitor was shown to inhibit bovine trypsin (Ki of 3.45 nM) at an
      approximate molar ratio of inhibitor:trypsin (1:1). The A- and B-chains revealed
      complete sequences of 140 and 40 amino acid residues, respectively. Sequence
      similarity (70%) was reported between ASTI A-chain and ACTI A-chain (Acacia
      confusa) using ClustalW. The B-chain produced a 76% sequence similarity between
      ASTI and Leucaena leucocephala trypsin inhibitor.

PMID- 24090422
TI  - Design, synthesis and molecular docking of novel N,N-dimethylbenzenesulfonamide
      derivatives as potential antiproliferative agents.
AB  - Novel pyridine, thiophene, thiazole, chromene and benzochromene derivatives
      bearing a N,N-dimethylbenzenesulfonamide moiety 6-20 were synthesized. The target
      compounds were obtained through employing a series of heterocyclization reactions
      utilizing the key intermediate hydrazide hydrazone derivative 3. The structures
      of the newly synthesized compounds were confirmed by elemental analyses, IR, (1)H
      NMR and (13)C-NMR spectral data. All the newly synthesized compounds were
      evaluated for their in vitro antiproliferative activity against the human breast
      cancer cell line MCF-7. Biological screening results showed that sulfonamides 6,
      9, 11, 16 and 17 with IC50 values 21.81, 25.50, 20.60, 25.83 and 31.20 MUM,
      respectively, possessed higher antiproliferative activity compared to
      doxorubicin, IC50 value 32.00 MUM, as position control. Molecular docking study
      was also performed to assess the binding mode of the synthesized sulfonamides
      with their potential biomolecular target, carbonic anhydrase IX (CA IX), which is
      usually highly expressed in some types of cancer cells.

PMID- 24090424
TI  - 5-Nitroisatin-derived thiosemicarbazones: potential antileishmanial agents.
AB  - A series of 29 previously reported N(4)-substituted 5-nitroisatin-3
      thiosemicarbazones 2-30 has been screened for leishmanicidal potential. Compounds
      2-4, 7, 8, 10-13, 15-19, 21, 23, 24, 26, 28 and 30 exhibited good to excellent
      antileishmanial activities with IC50 values ranging from 0.44 +/- 0.02 to 32.38
      +/- 0.66 ug/mL. Of these, 5, 7, 19 and 28 proved to be the most active
      antileishmanial agents, displaying activities with IC50 values 1.78 +/- 0.35,
      0.44 +/- 0.02, 1.91 +/- 0.04 and 4.28 +/- 0.75 ug/mL, respectively, which were
      even better than the standard drug, pentamidine (IC50 = 5.09 +/- 0.04 ug/mL).
      This study presents the first example of exhibition of leishmanicidal potential
      by isatin-thiosemicarbazones and as such furnishes a solid basis for further
      research on these compounds to develop more potent antileishmanial agents.

PMID- 24090423
TI  - Identification and structure-activity relationship study of carvacrol derivatives
      as Mycobacterium tuberculosis chorismate mutase inhibitors.
AB  - In the present study, we identified carvacrol, a major phenolic component of
      oregano oil as a novel small molecule inhibitor of Mycobacterium tuberculosis
      (MTB) chorismate mutase (CM) enzyme with IC50 of 1.06 +/- 0.4 uM. Virtual
      screening of the BITS-Pilani in-house database using the crystal structure of the
      MTB CM bound transition state intermediate (PDB: 2FP2) as framework identified
      carvacrol as a potential lead. Further various carvacrol derivatives were
      evaluated in vitro for their ability to inhibit MTB CM enzyme, whole cell MTB and
      cytotoxicity as steps toward the derivation of structure-activity relationships
      (SAR) and lead optimization.

PMID- 24090425
TI  - Design, synthesis and biological evaluation of 2-aminopyrimidinones and their 6
      aza-analogs as a new class of CK2 inhibitors.
AB  - In order to find the new potent CK2 inhibitors the 60 derivatives of 2
      aminopyrimidinone and their 6-aza-substituted analogs were synthesized and tested
      in vitro. Among them, the most efficient inhibitor 2-hydroxy-5-[4-(4
      methoxyphehyl)-6-oxo-1,6-dihydropyrimidin-2-ylamino] benzoic acid was identified
      (IC50 = 1.1 MUM). The structure--activity relationship study of newly synthesized
      derivatives was carried out and their binding mode with adenosine triphosphate
      acceptor site of CK2 was proposed.

PMID- 24090426
TI  - Sarcoplasmic reticulum Ca2+-ATPase from rabbit skeletal muscle modified by
      peroxynitrite.
AB  - OBJECTIVE: Effect of peroxynitrite on SERCA1 activity was studied in correlation
      with enzyme carbonylation. Kinetic parameters and location of peroxynitrite
      effect on SERCA1 were determined. METHODS: Carbonyls were determined by
      immunoblotting. FITC, NCD-4 and Trp fluorescence were used to indicate changes in
      cytosolic and transmembrane regions of SERCA1. RESULTS: Peroxynitrite
      concentration-dependent decrease of SERCA1 activity was associated with elevation
      of protein carbonyls. 4-HNE was not involved in carbonylation of SERCA1.
      Increased FITC fluorescence in the presence of peroxynitrite correlated with the
      decrease of the enzyme affinity to ATP. DISCUSSION AND CONCLUSION: Peroxynitrite
      induced SERCA1 carbonylation that was not accompanied with the formation of 4-HNE
      SERCA1 adducts is indicative of direct oxidation of SERCA1. As assessed by FITC
      fluorescence and decreased affinity of the enzyme to ATP, peroxynitrite
      impairment was found to occur in the cytosolic ATP-binding region of SERCA1.

PMID- 24090427
TI  - Effects of electromyostimulation on muscle and bone in men with acute traumatic
      spinal cord injury: A randomized clinical trial.
AB  - OBJECTIVE: To study the effect of 14 weeks of electromyostimulation (EMS)
      training (47 minutes/day, 5 days/week) on both muscle and bone loss prevention in
      persons with recent, complete spinal cord injury (SCI). DESIGN: Prospective,
      experimental, controlled, single-blind randomized trial with external blind
      evaluation by third parties. METHODS: Eight men with recent SCI (8 weeks from
      injury; ASIA Impairment Scale (AIS) "A") were randomized into the intervention or
      the control groups. Cross-sectional area of the quadriceps femoris (QF) muscle
      was quantified using magnetic resonance imaging. Bone mineral density changes
      were assessed with a dual-energy X-ray absorptiometry. Several bone biomarkers
      (i.e. total testosterone, cortisol, growth hormone, insulin-growth factor I,
      osteocalcin, serum type I collagen C-telopeptide), lipid, and lipoprotein
      profiles were quantified. A standard oral glucose tolerance test was performed
      before and after the 14-week training. All analyses were conducted at the
      beginning and after the intervention. RESULTS: The intervention group showed a
      significant increase in QF muscle size when compared with the control group. Bone
      losses were similar in both groups. Basal levels of bone biomarkers did not
      change over time. Changes in lipid and lipoprotein were similar in both groups.
      Glucose and insulin peaks moved forward after the training in the intervention
      group. CONCLUSIONS: This study indicates that skeletal muscle of patients with
      complete SCI retains the ability to grow in response to a longitudinal EMS
      training, while bone does not respond to similar external stimulus. Increases in
      muscle mass might have induced improvements in whole body insulin-induced glucose
      uptake.

PMID- 24090428
TI  - Simultaneous nondestructive analysis of palladium, rhodium, platinum, and gold
      nanoparticles using energy dispersive X-ray fluorescence.
AB  - A selective method is proposed for the determination of palladium, gold, and
      sulfur in catalytic systems, by direct liquid analysis using energy dispersive X
      ray fluorescence (EDXRF), under an atmosphere of helium or air. This method
      allows a nondestructive analysis of palladium, rhodium, platinum, and gold
      nanoparticulate catalysts stabilized by imidazolium propane sulfonate based
      zwitterionic surfactants, allowing the samples to be reused for catalytic
      studies. The signals from palladium, rhodium, platinum, and gold samples in the
      presence of imidazolium propane sulfonate-based zwitterionic surfactants obtained
      using EDXRF before (Pd(2+), Rh(2+), Pt(2+), and Au(3+)) and after (Pd(0), Rh(0),
      Pt(0), and Au(0)) formation of nanoparticles are essentially identical. The
      results show that the EDXRF method is nondestructive and allows detection and
      quantification of the main components of platinum, gold, rhodium, and palladium
      NPs, including the surfactant concentration, with detection and quantification
      limits in the range of 0.4-3 mg L(-1). The matrices used in such samples present
      no problems, even allowing the detection and quantification of interfering
      elements. 

PMID- 24090430
TI  - A key to understanding the effects of food bioactives in health, gut microbiota.

PMID- 24090429
TI  - RNA-Seq analysis of Citrus reticulata in the early stages of Xylella fastidiosa
      infection reveals auxin-related genes as a defense response.
AB  - BACKGROUND: Citrus variegated chlorosis (CVC), caused by Xylella fastidiosa, is
      one the most important citrus diseases, and affects all varieties of sweet orange
      (Citrus sinensis L. Osb). On the other hand, among the Citrus genus there are
      different sources of resistance against X. fastidiosa. For these species
      identifying these defense genes could be an important step towards obtaining
      sweet orange resistant varieties through breeding or genetic engineering. To
      assess these genes we made use of mandarin (C. reticulata Blanco) that is known
      to be resistant to CVC and shares agronomical characteristics with sweet orange.
      Thus, we investigated the gene expression in Ponkan mandarin at one day after
      infection with X. fastidiosa, using RNA-seq. A set of genes considered key
      elements in the resistance was used to confirm its regulation in mandarin
      compared with the susceptible sweet orange. RESULTS: Gene expression analysis of
      mock inoculated and infected tissues of Ponkan mandarin identified 667
      transcripts repressed and 724 significantly induced in the later. Among the
      induced transcripts, we identified genes encoding proteins similar to Pattern
      Recognition Receptors. Furthermore, many genes involved in secondary metabolism,
      biosynthesis and cell wall modification were upregulated as well as in synthesis
      of abscisic acid, jasmonic acid and auxin. CONCLUSIONS: This work demonstrated
      that the defense response to the perception of bacteria involves cell wall
      modification and activation of hormone pathways, which probably lead to the
      induction of other defense-related genes. We also hypothesized the induction of
      auxin-related genes indicates that resistant plants initially recognize X.
      fastidiosa as a necrotrophic pathogen.

PMID- 24090431
TI  - SFARI Gene 2.0: a community-driven knowledgebase for the autism spectrum
      disorders (ASDs).
AB  - New technologies enabling genome-wide interrogation have led to a large and
      rapidly growing number of autism spectrum disorder (ASD) candidate genes.
      Although encouraging, the volume and complexity of these data make it challenging
      for scientists, particularly non-geneticists, to comprehensively evaluate
      available evidence for individual genes. Described here is the Gene Scoring
      module within SFARI Gene 2.0 (https://gene.sfari.org/autdb/GS_Home.do), a
      platform developed to enable systematic community driven assessment of genetic
      evidence for individual genes with regard to ASD. 

PMID- 24090433
TI  - Li-ion adsorption and diffusion on two-dimensional silicon with defects: a first
      principles study.
AB  - Using first principles calculations we investigate the binding and diffusion of
      Li on silicene and evaluate the prospects for application to Li-ion batteries. We
      find that the defect formation energy for silicene is half that of graphene,
      showing that silicene is more likely to contain defects. The overall lithium
      adsorption energy on silicene with defects is greater than the bulk cohesive
      energy of lithium giving stability for use in storage. Our results predict high
      mobility for lithium atoms on the surface of silicene with energy barriers in the
      range of 0.28-0.30 eV. Further, we find that the diffusion barrier through
      silicene is significantly lower than the diffusion barrier through graphene, with
      a value of 0.05 eV for the double vacancy and 0.88 eV for the single vacancy. The
      low diffusion barriers, both on the surface and through the hollow site, suggest
      a suitable material for use in Li-ion batteries. 

PMID- 24090432
TI  - A fresh look at tobacco harm reduction: the case for the electronic cigarette.
AB  - Smokers of any age can reap substantial health benefits by quitting. In fact, no
      other single public health effort is likely to achieve a benefit comparable to
      large-scale smoking cessation. Surveys document that most smokers would like to
      quit, and many have made repeated efforts to do so. However, conventional smoking
      cessation approaches require nicotine addicted smokers to abstain from tobacco
      and nicotine entirely. Many smokers are unable--or at least unwilling--to achieve
      this goal, and so they continue smoking in the face of impending adverse health
      consequences. In effect, the status quo in smoking cessation presents smokers
      with just two unpleasant alternatives: quit or suffer the harmful effects of
      continuing smoking. But, there is a third choice for smokers: tobacco harm
      reduction. It involves the use of alternative sources of nicotine, including
      modern smokeless tobacco products like snus and the electronic cigarette (E-cig),
      or even pharmaceutical nicotine products, as a replacement for smoking. E-cigs
      might be the most promising product for tobacco harm reduction to date, because,
      besides delivering nicotine vapour without the combustion products that are
      responsible for nearly all of smoking's damaging effect, they also replace some
      of the rituals associated with smoking behaviour. Thus it is likely that smokers
      who switch to E-cigs will achieve large health gains. The focus of this article
      is on the health effects of using an E-cig, with consideration given to the
      acceptability, safety and effectiveness of this product as a long-term substitute
      for smoking.

PMID- 24090434
TI  - Effects of Allium victorialis leaf extracts and its single compounds on aldose
      reductase, advanced glycation end products and TGF-beta1 expression in mesangial
      cells.
AB  - BACKGROUND: Accumulating evidences suggest that aldose reductase (AR) inhibitors
      and advanced glycation end product (AGE) formation inhibitors may prevent chronic
      hyperglycemia-induced long-term complication in diabetes. Transforming growth
      factor-beta1 (TGF-beta1) plays an important role in the development of diabetic
      nephropathy. Allium species have been utilized in folk medicine throughout the
      world for the treatment of various physical disorders. However, the benefits of
      Allium victorialis (A. victorialis) against diabetic complications, especially
      nephropathy, have yet to be explored. In the present study, we investigated the
      protective effect of the compounds isolated from A. victorialis leaf on diabetic
      nephropathy. METHODS: In vitro AR activity, AGEs formation, and AGE-receptor for
      AGEs (RAGE) binding in human RAGE (hRAGE)-overexpressing cells were tested. High
      glucose-induced transforming growth factor-beta1 (TGF-beta1) expression was also
      examined in mouse kidney mesangial cells (MMCs) cultured under high glucose.
      RESULTS: Of the isolated eight compounds from A. victorialis leaf extracts
      tested, quercitrin exhibited the most pronounced inhibitory effects on AR
      activity (IC50 value of 0.17 MUM) and AGEs formation (IC50 value of 4.20 MUM).
      Furthermore, quercitrin disrupted AGE-RAGE binding in a concentration-dependent
      manner in hRAGE-overexpressing cells. Additionally, of the eight compounds
      tested, ferulic acid significantly reduced high glucose-induced TGF-beta1
      expression and secretion in MMCs. CONCLUSIONS: Our results suggest that active
      compounds isolated from A. victorialis leaf exhibit inhibitory effects on AR
      activity in rat lenses and AGE formation. Further, ferulic acid reduces TGF-beta1
      mRNA expression and secretion in MMCs under diabetic conditions. Thus, A.
      victorialis is a good candidate for the development of treatments for diabetic
      nephropathy.

PMID- 24090435
TI  - Dual-color nanoscale assemblies of structurally stable, few-atom silver clusters,
      as reported by fluorescence resonance energy transfer.
AB  - We develop approaches to hold fluorescent silver clusters composed of only 10-20
      atoms in nanoscale proximity, while retaining the individual structure of each
      cluster. This is accomplished using DNA clamp assemblies that incorporate a 10
      atom silver cluster and a 15 or 16 atom silver cluster. Thermally modulated
      fluorescence resonance energy transfer (FRET) verifies assembly formation.
      Comparison to Forster theory, using measured spectral overlaps, indicates that
      the DNA clamps hold clusters within roughly 5 to 6 nm separations, in the range
      of the finest resolutions achievable on DNA scaffolds. The absence of spectral
      shifts in dual-cluster FRET pairs, relative to the individual clusters, shows
      that select few-atom silver clusters of different sizes are sufficiently stable
      to retain structural integrity within a single nanoscale DNA construct. The
      spectral stability of the cluster persists in a FRET pair with an organic dye
      molecule, in contrast to the blue-shifted emission of the dye. 

PMID- 24090436
TI  - Hydroxyethyl starch 130/0.4 or hypertonic saline solution to decrease
      inflammatory response in hemorrhagic shock?

PMID- 24090437
TI  - Interaction of insulin-enhancing vanadium compounds with human serum holo
      transferrin.
AB  - The interaction of VO(2+) ion and four insulin-enhancing compounds, [VO(ma)2],
      [VO(dhp)2], [VO(acac)2], and cis-[VO(pic)2(H2O)], where Hma, Hdhp, Hacac, and
      Hpic are maltol, 1,2-dimethyl-3-hydroxy-4(1H)-pyridinone, acetylacetone, and
      picolinic acid, with holo-transferrin (holo-hTf) was studied through the combined
      application of electron paramagnetic resonance (EPR) and density functional
      theory (DFT) methods. Since in holo-hTf all of the specific binding sites of
      transferrin are saturated by Fe(3+) ions, VO(2+) can interact with surface sites
      (here named sites C), probably via the coordination of His-N, Asp-COO(-), and Glu
      COO(-) donors. In the ternary systems with the insulin-enhancing compounds, mixed
      species are observed with Hma, Hdhp, and Hpic with the formation of VOL2(holo
      hTf), explained through the interaction of cis-[VOL2(H2O)] (L = ma, dhp) or cis
      [VOL2(OH)](-) (L = pic) with an accessible His residue that replaces the
      monodentate H2O or OH(-) ligand. The residues of His-289, His-349, His-473, and
      His-606 seem the most probable candidates for the complexation of the cis-VOL2
      moiety. The lack of a ternary complex with Hacac was attributed to the square
      pyramidal structure of [VO(acac)2], which does not possess equatorial sites that
      can be replaced by the surface His-N. Since holo-transferrin is recognized by the
      transferrin receptor, the formation of ternary complexes between VO(2+) ion, a
      ligand L(-), and holo-hTf may be a way to transport vanadium compounds inside the
      cells. 

PMID- 24090438
TI  - Culture and math.
AB  - Cultural differences have been shown across a number of different cognitive
      domains from vision, language, and music. Mathematical cognition is another
      domain that is an integral part of modern society and because there are a fixed
      number of ways in which many math operations can be performed, it is also an
      apposite tool for cultural comparisons. This discussion examines the literature
      on mathematical processing in accordance with culture, summarizing the brain
      regions involved across various mathematical tasks. In doing so, we provide a
      clear picture of the anatomical similarities and differences between cultures
      when performing different math tasks. This information is useful to explore the
      possibility of enhancement of mathematical skills, where different strategies may
      be applicable in accordance with culture. It also contributes to the evolutionary
      development of different math skills and the growing theory that anatomical and
      behavioral studies must account for the cultural identity of their sample. 

PMID- 24090439
TI  - Hyperthyroid state or in vitro thyroxine treatment modulates TH1/TH2 responses
      during exposure to HSV-1 antigens.
AB  - Increasingly in recent years, thyroid hormones (THs) have been considered to be
      important regulators of the immune system. However, their roles in host defense
      against viral infections are not clearly established. Therefore, this study was
      undertaken to examine proliferative activity and cytokine production by
      lymphocytes isolated from hyperthyroid and euthyroid Balb/c mice in response to
      herpes simplex virus-1 (HSV-1). Lymphocytes of hyperthyroid animals showed a
      significantly higher rate of proliferation and interferon (IFN)-gamma production
      when compared with that by lymphocytes from euthyroid mice. In vitro thyroxine
      (T4) treatment was similarly effective in the potentiation of proliferation, but
      not IFNgamma production, by euthyroid lymphocytes. Furthermore, the hyperthyroid
      state significantly attenuated ConA-, but not HSV-1-, induced interleukin (IL)-10
      release; in vitro T4 treatment synergized this effect. These findings suggest
      that supra-physiologic TH levels (i.e. as occur in hyper-thyroid states) or in
      vitro TH treatment modulate T-helper (TH)1/TH2 lymphocyte responses and thereby
      amplifies host defenses against viral infections. One may also conclude that THs
      may have a potential application in viral immunization and/or treatment of viral
      infections.

PMID- 24090440
TI  - Biolimus-eluting stent with biodegradable polymer (Nobori(r)): an overview of
      recent clinical results, SORT OUT V and COMPARE II trials.
AB  - Since their apparition, first generation drug-eluting stents (DESs) have raised
      concerns regarding the risk of late and very late stent thrombosis as compared to
      bare metal stents and require prolonged dual antiplatelet therapy. Aside from
      delayed strut endothelialisation, positive vessel remodelling and late stent mal
      apposition due to chronic inflammation may be a leading cause for these stent
      thromboses. In fact, the persistence of the durable polymer after complete drug
      release is responsible for local hypersensitivity and inflammatory reactions.
      Third generation DESs with biocompatible or biodegradable polymer have
      subsequently been developed to address this issue. In this article, we evaluate
      and discuss the results of two recent publications investigating safety and
      efficacy of a third generation DES with biodegradable polymer as compared to
      first and second generation DESs with durable polymer.

PMID- 24090442
TI  - Two-year outcomes for infants with low cord pH at birth.
AB  - OBJECTIVE: To determine the long-term outcome of infants born with cord pH <= 7.0
      and no clinical evidence of asphyxia at birth. DESIGN:  SETTING: Tertiary
      Referral Centre. A prospective matched cohort study was conducted. 51 term
      infants were recruited following singleton birth with venous cord pH <= 7.0. For
      each recruited baby a healthy baby with normal cord pH >= 7.20 was recruited
      matched for gestation, gender and mode of delivery. Ages and Stages
      Questionnaires (ASQ)(TM) and Health Screening Questionnaires (HSQ) were sent out
      at 24 months of age. Two independent assessors, blinded to the case assignment,
      reviewed intrapartum and neonatal events to look for clinical evidence of birth
      asphyxia among the cases. RESULT: From 102 infants recruited, 62 questionnaires
      (24 cases, 38 controls) were returned. 20 matched pairs with no clinical evidence
      of birth asphyxia were available for analysis. The groups were similar except in
      terms of birth weight; the pH >= 7.0 group had mean birth weight 584 g lower than
      controls (p = 0.005). The ASQ motor scores were lower in children born with low
      cord pH (p = 0.019); however, once adjusted for birth weight, the difference was
      not significant (p = 0.289). CONCLUSION: It is unlikely that abnormal cord pH in
      otherwise healthy neonates leads to a substantially increased risk of abnormal
      neurodevelopmental outcome or severe health problems by 2 years of age.

PMID- 24090441
TI  - Combining freshly isolated chondroprogenitor cells from the infrapatellar fat pad
      with a growth factor delivery hydrogel as a putative single stage therapy for
      articular cartilage repair.
AB  - Growth factor delivery systems incorporating chondroprogenitor cells are an
      attractive potential treatment option for damaged cartilage. The rapid isolation,
      processing, and implantation of therapeutically relevant numbers of autologous
      chondroprogenitor cells, all performed "in-theatre" during a single surgical
      procedure, would significantly accelerate the clinical translation of such tissue
      engineered implants by avoiding the time, financial and regulatory challenges
      associated with in vitro cell expansion, and differentiation. The first objective
      of this study was to explore if rapid adherence to a specific substrate could be
      used as a simple means to quickly identify a subpopulation of chondroprogenitor
      cells from freshly digested infrapatellar fat pad (IFP) tissue. Adhesion of cells
      to tissue culture plastic within 30 min was examined as a mechanism of isolating
      subpopulations of cells from the freshly digested IFP. CD90, a cell surface
      marker associated with cell adhesion, was found to be more highly expressed in
      rapidly adhering cells (termed "RA" cells) compared to those that did not adhere
      (termed "NA" cells) in this timeframe. The NA subpopulation contained a lower
      number of colony forming cells, but overall had a greater chondrogenic potential
      but a diminished osteogenic potential compared to the RA subpopulation and
      unmanipulated freshly isolated (FI) control cells. When cultured in agarose
      hydrogels, NA cells proliferated faster than RA cells, accumulating significantly
      higher amounts of total sGAG and collagen. Finally, we sought to determine if
      cartilage tissue could be engineered by seeding such FI cells into a transforming
      growth factor-beta3 delivery hydrogel. In such a system, both RA and NA cell
      populations demonstrated an ability to proliferate and produced a matrix rich in
      sGAG (~2% w/w) that stained positively for type II collagen; however, the tissues
      were comparable to that generated using FI cells. Therefore, while the results of
      these in vitro studies do not provide strong evidence to support the use of
      selective substrate adhesion as a means to isolate chondroprogenitor cells, the
      findings demonstrate the potential of combining a growth factor delivery hydrogel
      and FI IFP cells as a single stage therapy for cartilage defect repair. 

PMID- 24090443
TI  - Expeditious synthesis, enantiomeric resolution, and enantiomer functional
      characterization of (4-(4-bromophenyl)-3a,4,5,9b-tetrahydro-3H
      cyclopenta[c]quinoline-8-sulfonamide (4BP-TQS): an allosteric agonist-positive
      allosteric modulator of alpha7 nicotinic acetylcholine receptors.
AB  - An expeditious microwave-assisted synthesis of 4BP-TQS, its enantiomeric
      separation, and their functional evaluation is reported. Electrophysiological
      characterization in Xenopus oocytes revealed that activity exclusively resided in
      the (+)-enantiomer 1b (GAT107) and (-)-enantiomer 1a did not affect its activity
      when coapplied. X-ray crystallography studies revealed the absolute
      stereochemistry of 1b to be 3aR,4S,9bS. 1b represents the most potent ago-PAM of
      alpha7 nAChRs available to date and is considered for further in vivo evaluation.

PMID- 24090444
TI  - Reaction of cyclic alpha-oxoketene dithioacetals with methylene isocyanides: a
      novel pyrrole annulation-ring-expansion domino process.
AB  - The title reaction provides a direct entry to a range of biologically relevant
      annulated pyrroles via a domino process involving a regioselective one-carbon
      homologation of cyclic ketones as the key step. 

PMID- 24090445
TI  - Idiopathic acute transverse myelitis: outcome and conversion to multiple
      sclerosis in a large series.
AB  - BACKGROUND: In 2002, the Transverse Myelitis Consortium Working Group (TMCWG)
      proposed the diagnostic criteria for idiopathic acute transverse myelitis (IATM)
      to delimit and unify this group of patients. This study aimed to describe the
      conversion rate to multiple sclerosis (MS) and variables associated with
      conversion, and to analyze functional outcome and prognostic factors associated
      with functional recovery in patients who fulfilled the current TMCWG criteria for
      definite and possible IATM. METHODS: Eighty-seven patients diagnosed with IATM
      between 1989 and 2011 were retrospectively reviewed. Two patients with positive
      neuromyelitis optica IgG serum antibodies were excluded. Epidemiological,
      clinical, laboratory, magnetic resonance imaging (MRI) data and outcome of 85
      patients were analyzed. RESULTS: Eleven (13%) patients converted to MS after a
      median follow-up of 2.9 years (interquartile range 1.0-4.8). Early-age onset of
      symptoms was related to conversion to MS. Only 9.4% of patients with IATM were
      unable to walk unassisted at the end of follow-up. Urinary sphincter dysfunction
      (odds ratio [OR] 3.37, 95% confidence interval [CI] 1.04-10.92) and
      longitudinally extensive transverse myelitis (LETM) on MRI (OR 12.34, 95% CI 3.38
      45.00) were associated with a poorer outcome (Rankin >= 2). CONCLUSIONS: At least
      13% of patients who fulfill the TMCWG criteria for definite and possible IATM
      will convert to MS. Functional recovery in IATM is poorer in patients with
      urinary sphincter dysfunction at admission or LETM on MRI.

PMID- 24090446
TI  - Urban-like night illumination reduces melatonin release in European blackbirds
      (Turdus merula): implications of city life for biological time-keeping of
      songbirds.
AB  - INTRODUCTION: Artificial light-at-night is known to affect a broad array of
      behaviours and physiological processes. In urbanized bird species, light-at-night
      advances important biological rhythms such as daily cycles of activity/rest and
      timing of reproduction, but our knowledge of the underlying physiological
      mechanisms is limited. Given its role as chronobiological signal, melatonin is a
      strong candidate for mediating the effects of light-at-night. RESULTS: We exposed
      urban and rural European blackbirds (Turdus merula) to two light treatments equal
      in photoperiod but with different light intensities at night. The control group
      was exposed to 0.0001 lux (almost darkness), while the experimental group was
      exposed to 0.3 lux at night, simulating conditions recorded previously on free
      living urban blackbirds. We obtained diel profiles of plasma melatonin for all
      birds in summer (July) and winter (January), while simultaneously recording
      locomotor activity. Daily patterns of melatonin concentrations were clearly
      affected by light-at-night in both seasons. In winter, melatonin concentrations
      of light-at-night birds were lower in the early and late night than in those of
      birds kept in darkness. In summer, melatonin concentrations of the light-at-night
      birds were lower through all night compared to birds kept in darkness. Locomotor
      activity in light-at-night birds was overall higher than in control individuals,
      both during the day and at night, and it increased sharply before dawn. In
      winter, the amount of activity before dawn in the light-at-night group correlated
      with changes in melatonin from midnight to late night: the greater the decrease
      in melatonin, the greater the amount of pre-dawn activity. Urban and rural birds
      responded similarly to light-at-night with respect to melatonin, but differed in
      their behaviour, with rural birds showing more locomotor activity than urban
      counterparts. CONCLUSIONS: This study points to reduced melatonin release at
      night as a potential physiological mechanism underlying the advanced onset of
      morning activity of urbanized birds. Based on the pattern of melatonin secretion,
      we suggest that birds responded to light-at-night as if they were exposed to a
      longer day than birds kept under dark nights.

PMID- 24090447
TI  - External cues benefit walking ability of ambulatory patients with spinal cord
      injury.
AB  - BACKGROUND/OBJECTIVES: Sensorimotor dysfunction following spinal cord injury
      (SCI) reduces ability of the patients to perceive information and control
      movements. They may need alternative sources of input to optimize their walking
      ability. This study investigated effects of external cues on walking ability in
      33 independent ambulatory participants with SCI. METHODS: Participants' walking
      ability was cross-sectionally assessed under three conditions including self
      determined fastest walking speed (uncued condition), and fastest walking speed
      with the use of external cues (visual cue and visuotemporal cue conditions).
      Walking ability was measured in terms of walking speed, stride length, cadence,
      and percent step symmetry. Findings of the three conditions were compared using
      the one-way analysis of variance with repeated measures. RESULTS: When using
      external cues particularly the visuotemporal cue, participants showed a
      significant increase in walking speed, stride length, and cadence as compared
      with those of the uncued condition (P < 0.005). The increment of walking speed
      was demonstrated even in participants at a chronic stage of injury (post-injury
      time >= 12 months), with severe SCI (American Spinal Injury Association
      Impairment Scale C), or who required a walking device. CONCLUSION: The results
      suggested the benefit of external cues, particularly the visuotemporal cues, as a
      potential rehabilitation tool to improve walking speed of individuals with SCI.

PMID- 24090448
TI  - Modulation of a protein free-energy landscape by circular permutation.
AB  - Circular permutations usually retain the native structure and function of a
      protein while inevitably perturbing its folding dynamics. By using simulations
      with a structure-based model and a rigorous methodology to determine free-energy
      surfaces from trajectories, we evaluate the effect of a circular permutation on
      the free-energy landscape of the protein T4 lysozyme. We observe changes which,
      although subtle, largely affect the cooperativity between the two subdomains.
      Such a change in cooperativity has been previously experimentally observed and
      recently also characterized using single molecule optical tweezers and the Crooks
      relation. The free-energy landscapes show that both the wild type and circular
      permutant have an on-pathway intermediate, previously experimentally
      characterized, in which one of the subdomains is completely formed. The
      landscapes, however, differ in the position of the rate-limiting step for
      folding, which occurs before the intermediate in the wild type and after in the
      circular permutant. This shift of transition state explains the observed change
      in the cooperativity. The underlying free-energy landscape thus provides a
      microscopic description of the folding dynamics and the connection between
      circular permutation and the loss of cooperativity experimentally observed. 

PMID- 24090449
TI  - Optogenetic control of protein kinase activity in mammalian cells.
AB  - Light-dependent dimerization is the basis for recently developed noninvasive
      optogenetic tools. Here we present a novel tool combining optogenetics with the
      control of protein kinase activity to investigate signal transduction pathways.
      Mediated by Arabidopsis thaliana photoreceptor cryptochrome 2, we activated the
      protein kinase C-RAF by blue light-dependent dimerization, allowing for
      decoupling from upstream signaling events induced by surface receptors. The
      activation by light is fast, reversible, and not only time but also dose
      dependent as monitored by phosphorylation of ERK1/2. Additionally, light
      activated C-RAF controls serum response factor-mediated gene expression. Light
      induced heterodimerization of C-RAF with a kinase-dead mutant of B-RAF
      demonstrates the enhancing role of B-RAF as a scaffold for C-RAF activity, which
      leads to the paradoxical activation of C-RAF found in human cancers. This
      optogenetic tool enables reversible control of protein kinase activity in signal
      duration and strength. These properties can help to shed light onto downstream
      signaling processes of protein kinases in living cells. 

PMID- 24090451
TI  - Pyrolyzed carbon film diodes.
AB  - We have previously reported pyrolyzed parylene C (PPC) as a conductive carbon
      electrode material for use with micropipets, atomic force microscopy probes, and
      planar electrodes. Advantages of carbon electrode fabrication from PPC include
      conformal coating of high-aspect ratio micro/nanoscale features and the benefits
      afforded by chemical vapor deposition of carbon polymers. In this work, we
      demonstrate chemical surface doping of PPC through the use of previously reported
      methods. Chemically treated PPC films are characterized by multiple spectroscopic
      and electronic measurements. Pyrolyzed parylene C and doped PPC are used to
      construct diodes that are examined as both p-n heterojunction and Schottky
      barrier diodes. Half-wave rectification is achieved with PPC diodes and
      demonstrates the applicability of PPC as a conductive and semiconductive material
      in device fabrication. 

PMID- 24090450
TI  - Associations with chest illness and mortality in chronic spinal cord injury.
AB  - OBJECTIVE: Identify factors associated with chest illness and describe the
      relationship between chest illness and mortality in chronic spinal cord injury
      (SCI). DESIGN: Cross-sectional survey assessing chest illness and a prospective
      assessment of mortality. METHODS: Between 1994 and 2005, 430 persons with chronic
      SCI (mean +/- SD), 52.0 +/- 14.9 years old, and >=4 years post SCI (20.5 +/- 12.5
      years) underwent spirometry, completed a health questionnaire, and reported any
      chest illness resulting in time off work, indoors, or in bed in the preceding 3
      years. Deaths through 2007 were identified. Outcome measures Logistic regression
      assessing relationships with chest illness at baseline and Cox regression
      assessing the relationship between chest illness and mortality. RESULTS: Chest
      illness was reported by 139 persons (32.3%). Personal characteristics associated
      with chest illness were current smoking (odds ratio =2.15; 95% confidence
      interval =1.25-3.70 per each pack per day increase), chronic obstructive
      pulmonary disease (COPD) (3.52; 1.79-6.92), and heart disease (2.18; 1.14-4.16).
      Adjusting for age, subjects reporting previous chest illness had a non
      significantly increased hazard ratio (HR) for mortality (1.30; 0.88-1.91). In a
      multivariable model, independent predictors of mortality were greater age, SCI
      level and completeness of injury, diabetes, a lower %-predicted forced expiratory
      volume in 1 second, heart disease, and smoking history. Adjusting for these
      covariates, the effect of a previous chest illness on mortality was attenuated
      (HR = 1.15; 0.77-1.73). CONCLUSION: In chronic SCI, chest illness in the
      preceding 3 years was not an independent risk factor for mortality and was not
      associated with level and completeness of SCI, but was associated with current
      smoking, physician-diagnosed COPD, and heart disease history.

PMID- 24090452
TI  - Potential roles of metallothioneins I and II in protecting bone growth following
      acute methotrexate chemotherapy.
AB  - Metallothioneins (MTs) are known to participate in protection against oxidative
      stress. This study assessed the effects of MT-I&II gene knockout on methotrexate
      (MTX)-induced bone damage in growing mice. MT-I&II knockout (MT-/-) and wild type
      (MT+/+) male mice were injected with saline or 12.5 mg kg-1 MTX for three
      consecutive days. MTX treatment was shown to cause more severe damage in MT-/-
      mice when compared to MT+/+ mice, as demonstrated by the more obvious thinning of
      growth plate, reduced proliferation and increased apoptosis of chondrocytes, and
      reduced metaphysis heights in the knockout mice. Analysis of total liver
      glutathione (the most abundant intracellular antioxidant) also revealed
      significant lower glutathione levels in all MT-/- mice. In conclusion, MT-/- mice
      were more susceptible than MT+/+ mice to MTX-induced bone damages, which may be
      associated with the reduction of basal antioxidant defence, suggesting a
      protective role of MTs in the growing skeleton against damages caused by MTX
      chemotherapy.

PMID- 24090453
TI  - Molecular dyads of ruthenium(II)- or osmium(II)-bis(terpyridine) chromophores and
      expanded pyridinium acceptors: equilibration between MLCT and charge-separated
      excited states.
AB  - The synthesis, characterization, redox behavior, and photophysical properties
      (both at room temperature in fluid solution and at 77 K in rigid matrix) of a
      series of four new molecular dyads (2-5) containing Ru(II)- or Os(II)
      bis(terpyridine) subunits as chromophores and various expanded pyridinium
      subunits as electron acceptors are reported, along with the reference properties
      of a formerly reported dyad, 1. The molecular dyads 2-4 have been designed to
      have their (potentially emissive) triplet metal-to-ligand charge-transfer (MLCT)
      and charge-separated (CS) states close in energy, so that excited-state
      equilibration between these levels can take place. Such a situation is not shared
      by limit cases 1 and 5. For dyad 1, forward photoinduced electron transfer (time
      constant, 7 ps) and subsequent charge recombination (time constant, 45 ps) are
      evidenced, while for dyad 5, photoinduced electron transfer is thermodynamically
      forbidden so that MLCT decays are the only active deactivation processes. As
      regards 2-4, CS states are formed from MLCT states with time constants of a few
      dozens of picoseconds. However, for these latter species, such experimental time
      constants are not due to photoinduced charge separation but are related to the
      excited-state equilibration times. Comparative analysis of time constants for
      charge recombination from the CS states based on proper thermodynamic and kinetic
      models highlighted that, in spite of their apparently affiliated structures,
      dyads 1-4 do not constitute a homologous series of compounds as far as
      intercomponent electron transfer processes are concerned. 

PMID- 24090454
TI  - Dermatological problems following spinal cord injury in Korean patients.
AB  - OBJECTIVE: To identify dermatological conditions following spinal cord injury
      (SCI) and analyze these conditions in relation to various characteristics of SCI.
      DESIGN: Retrospective chart review. SETTING: National Health Insurance
      Corporation Ilsan Hospital of Korea, Rehabilitation Center, Spinal Cord Unit.
      PARTICIPANTS: Patients treated for SCI who were referred to dermatology for
      dermatological problems, 2000-2012. RESULTS: Of the 1408 SCI patients treated at
      the spinal cord unit, 253 patients with SCI were identified to have been referred
      to dermatology for skin problems and a total of 335 dermatological conditions
      were diagnosed. The most common dermatological finding was infectious (n = 123,
      36.7%) followed by eczematous lesions (n = 109, 32.5%). Among the infectious
      lesions, fungal infection (n = 76, 61.8%) was the most common, followed by
      bacterial (n = 27, 21.9%) lesions. Seborrheic dermatitis (n = 59, 64.1%) was the
      most frequent eczematous lesion. Ingrown toenail occurred more frequently in
      tetraplegics whereas vascular skin lesions occurred more commonly in patients
      with paraplegia (P < 0.05). Xerotic dermatitis showed a higher occurrence within
      12 months of injury rather than thereafter (P < 0.05). Of these, 72.4% of the
      infectious and 94.7% of the fungal skin lesions manifested below the neurological
      level of injury (NLI; P < 0.001) and 61.5% of the eczematous lesions and 94.9% of
      seborrheic dermatitis cases occurred above the NLI (P < 0.001). There was no
      significant difference in dermatological diagnoses between patients with
      neurologically complete and incomplete SCI. CONCLUSION: The most common
      dermatological condition in patients with SCI among those referred to dermatology
      was fungal infection, followed by seborrheic dermatitis. Although dermatological
      problems after SCI are not critical in SCI outcome, they negatively affect the
      quality of life. Patients and caregivers should be educated about appropriate
      skin care and routine dermatological examinations.

PMID- 24090455
TI  - Characterization of Shiga toxin - producing Escherichia coli infections in beef
      feeder calves and the effectiveness of a prebiotic in alleviating Shiga toxin -
      producing Escherichia coli infections.
AB  - BACKGROUND: In the less-sensitive mouse model, Shiga toxin-producing Escherichia
      coli (STEC) challenges result in shedding that reflect the amount of infection
      and the expression of virulence factors such as Shiga toxins (Stx). The purpose
      of this study was to characterize the contribution of STEC diversity and Stx
      expression to shedding in beef feeder calves and to evaluate the effectiveness of
      a prebiotic, Celmanax(r), to alleviate STEC shedding. Fecal samples were
      collected from calves at entry and after 35 days in the feedlot in spring and
      summer. STECs were evaluated using selective media, biochemical profile,
      serotyping and Stx detection. Statistical analysis was performed using repeated
      measures ANOVA and logistic regression. RESULTS: At entry, non-O157 STEC were
      dominant in shedding calves. In spring, 21%, 14% and 14% of calves acquired O157,
      non-O157 and mixed STEC infections, respectively. In contrast, 45%, 48% and 46%
      of calves in summer acquired O157, non-O157 and mixed STEC infections,
      respectively. Treatment with a prebiotic, Celmanax(r), in spring significantly
      reduced 50% of the O157 STEC infections, 50% of the non-O157 STEC infections and
      36% of the STEC co-infections (P = 0.037). In summer, there was no significant
      effect of the prebiotic on STEC infections. The amount of shedding at entry was
      significantly related to the number and type of STECs present and Stx expression
      (r2 = 0.82). The same relationship was found for shedding at day 35 (r2 = 0.85),
      but it was also related to the number and type of STECs present at entry. Stx -
      producing STEC infections resulted in 100 to 1000 * higher shedding in calves
      compared with Stx-negative STECs. CONCLUSIONS: STEC infections in beef feeder
      calves reflect the number and type of STECs involved in the infection and STEC
      expression of Stx. Application of Celmanax(r) reduced O157 and non-O157 STEC
      shedding by calves but further research is required to determine appropriate
      dosages to manage STEC infections.

PMID- 24090456
TI  - Protective effects of Zhuyeqing liquor on the immune function of normal and
      immunosuppressed mice in vivo.
AB  - BACKGROUND: Zhuyeqing Liquor (ZYQL), a well-known Chinese traditional health
      liquor, has various biological properties, including anti-oxidant, anti
      inflammatory, immunoenhancement and cardiovascular protective effects. METHODS:
      The protective effects of Zhuyeqing Liquor (ZYQL) on the immune function was
      investigated in vivo in normal healthy mice and immunosuppressed mice treated
      with Cyclophosphamide (Cy, 100 mg/kg) by intraperitoneal injection on days 4, 8
      and 12. ZYQL (100, 200 and 400 mg/kg) was administered via gavage daily for 14
      days. The phagocytotic function of mononuclear phagocytic system was detected
      with carbon clearance methods, the levels of interleukin-6 (IL-6) and interferon
      gamma (IFN-gamma) in serum were detected with Enzyme linked immunosorbent assay
      (ELISA). Immune organs were weighed and organ indexes (organ weight/body weight)
      of thymus and spleen were calculated. Meanwhile, the activity of lysozyme (LSZ)
      in serum and the activity of superoxide dismutase (SOD), glutathione peroxidase
      (GSH-Px), catalase (CAT) in spleen tissue were measured. RESULTS: ZYQL
      significantly upgrades the K value for clearance of carbon particles in normal
      mice treated with ZYQL (400 mg/kg) and immunosuppressed mice treated with ZYQL
      (100, 200 and 400 mg/kg) together with Cy (100 mg/kg) in vivo. The treatment of
      ZYQL (100, 200 and 400 mg/kg) effectively increased the activity of serum
      lysozyme as well as promoted the serum levels of IL-6 and IFN-gamma in normal
      mice and immunosuppressed mice. Furthermore, ZYQL (100, 200 and 400 mg/kg) had an
      antioxidant effects in immune system by enhancing the antioxidant enzyme activity
      of SOD, CAT and GSH-Px in vivo. In addition, ZYQL (100, 200 and 400 mg/kg)
      effectively elevated the Cy-induced decreased organ index (thymus and spleen).
      CONCLUSIONS: The present work shows that the dose-dependent administration of
      ZYQL is capable of influencing immune responses, which implying that its valuable
      functional health may be attributed partly to its protective effects for the
      immune function.

PMID- 24090457
TI  - Bone marrow suppression or active proliferation? An analysis of neutropenia after
      pegylated interferon treatment of patients with chronic hepatitis C.
AB  - BACKGROUND: Neutropenia is a common adverse effect of the treatment of chronic
      hepatitis C with pegylated interferon and ribavirin. However, the mechanism
      involved is unknown. The present study aimed to investigate the cause of
      treatment-induced neutropenia by determining cytokine levels in plasma and in
      bone marrow smears. METHODS: Fifteen patients with chronic hepatitis C were
      enrolled in this study. Plasma cytokine levels were determined using the Luminex
      assay before and during treatment. We simultaneously determined the levels of
      granulocyte colony-stimulating factor (G-CSF), granulocyte-macrophage colony
      stimulating factor (GM-CSF), and 7 other cytokines, and performed bone marrow
      cytology when blood cell counts indicated neutropenia. RESULTS: Only 1 bone
      marrow smear indicated a low cell proliferation level, whereas active
      proliferation was observed in the remaining 14 patients. The levels of G-CSF, GM
      CSF, interleukin (IL)-2, IL-4, IL-6, and interferon (IFN)-gamma decreased
      significantly in patients with neutropenia (p < 0.05). In contrast, the levels of
      IL-8, IL-10, and tumor necrosis factor (TNF)-alpha showed no significant change
      (p = 0.713, 0.930, 0.833, respectively) before or after treatment. CONCLUSIONS:
      The bone marrow of most patients with IFN-induced neutropenia showed active cell
      proliferation. Elevated G-CSF and GM-CSF but not bone marrow suppression was
      observed along with neutropenia after pegylated interferon treatment, suggesting
      a causative role of G-CSF and GM-CSF in neutropenia.

PMID- 24090458
TI  - High-throughput screening of colonization samples for methicillin-resistant
      Staphylococcus aureus.
AB  - BACKGROUND: We present here the first application of 2-photon excited
      fluorescence detection (TPX) technology for the direct screening of clinical
      colonization samples for methicillin-resistant Staphylococcus aureus (MRSA).
      METHODS: A total of 125 samples from 14 patients with previously identified MRSA
      carriage and 16 controls from low-prevalence settings were examined. RESULTS: The
      results were compared to those obtained by both standard phenotypic and molecular
      methods. In identifying MRSA carriers, i.e. persons with at least 1 MRSA positive
      colonization sample by standard methods, the sensitivity of the TPX technique was
      100%, the specificity 78%, the positive predictive value 75%, and the negative
      predictive value 100%. The TPX assay sensitivity per colonization sample was 89%,
      the specificity 93%, the positive predictive value 84%, and the negative
      predictive value 95%. The median time for a true-positive test result was 3 h and
      26 min; negative test results are available after 13 h. The assay capacity was 48
      samples per test run. CONCLUSIONS: The TPX MRSA technique could provide early
      preliminary results for clinicians, while simultaneously functioning as a
      selective enrichment step for further conventional testing. Costs and workload
      associated with hospital infection control can be reduced using this high
      throughput, point-of-care compatible methodology.

PMID- 24090459
TI  - The quality of life in patients during intravesical treatment and correlation
      with local symptoms.
AB  - OBJECTIVE: To evaluate the quality of life (QoL) in patients who had undergone
      intravesical treatment for non-muscle invasive bladder cancer and analyse the
      correlation between QoL and local symptoms. METHODS: A total of 106 non-muscle
      invasive bladder cancer patients were enrolled. Quality of life was measured
      using the Chinese version of the European Organization for Research and Treatment
      of Cancer Quality of Life Questionnaire (EORTC QLQ-C30). Local symptoms were
      measured with Core Lower Urinary Tract Symptom Score (CLSS) questionnaire. Both
      questionnaires were administered before starting the instillation and after
      instillation. The correlation between local symptoms and QoL was analyzed.
      RESULTS: Quality of life was significantly impaired by intravesical treatment.
      The scores of global health status and social functioning significantly decreased
      from 83.3+/-11.8 and 100 to 74.5+/-17.2 and 83.6+/-15.4 respectively. The
      symptoms of pain, diarrhea, and financial difficulties scored higher than that of
      baseline. The CLSS and QoL index increased significantly compared to baseline.
      The scores of global health status and pain were significant associated with
      CLSS. CONCLUSION: Long-term intravesical treatment could decline the QoL of
      patients. Local symptom was an important factor found to be associated with
      impairment of QoL. Appropriate therapy for local symptoms might improve the
      patients' overall QoL.

PMID- 24090460
TI  - Down syndrome: Past concerns and future promises.

PMID- 24090461
TI  - Prenatal screening for Down syndrome in Australia: costs and benefits of current
      and novel screening strategies.
AB  - OBJECTIVE: To analyse the cost-effectiveness and performance of noninvasive
      prenatal testing (NIPT) for high-risk pregnancies following first-trimester
      screening compared with current practice. METHODS: A decision tree analysis was
      used to compare the costs and benefits of current practice of first-trimester
      screening with a testing pathway incorporating NIPT. We applied the model to 32
      478 singleton pregnancies screened between January 2005 and December 2006, adding
      Medicare rebate data as a measure of public health system costs. The analyses
      reflect the actual uptake of screening and diagnostic testing and pregnancy
      outcomes in this cohort. RESULTS: The introduction of NIPT would reduce the
      number of invasive diagnostic procedures and procedure-related fetal losses in
      high-risk women by 88%. If NIPT was adopted by all women identified as high risk
      by first-trimester combined screening, up to 7 additional Down syndrome fetuses
      could be confirmed. The cost per trisomy 21 case confirmed, including NIPT was
      9.7% higher ($56,360) than the current prenatal testing strategy ($51,372) at a
      total cost of $3.91 million compared with $3.57 million over 2 years. CONCLUSION:
      Based on the uptake of screening and diagnostic testing in a retrospective cohort
      of first-trimester screening in Western Australia, the implementation of NIPT
      would reduce the number of invasive diagnostic tests and the number of procedure
      related fetal losses and increase the cost by 9.7% over two years. Policy
      planning and guidelines are urgently required to manage the funding and demand
      for NIPT services in Australia.

PMID- 24090462
TI  - The quality of consent - what is the evidence?
AB  - The documentation of consent is an important component of the clinical encounter.
      This study assesses the quality of documentation of that consent for a common
      surgical procedure, caesarean section, in an obstetric unit at a major teaching
      hospital and compares this quality between elective and emergency cases. There
      was a significant difference in the quality of documentation between the elective
      and emergency groups in some, but not all, categories assessed. Overall, the
      standard of consent documentation in the obstetric unit was less than desired. A
      proforma was designed to be included in the case notes of women undergoing
      caesarean section to improve the efficient and thorough documentation of consent.

PMID- 24090463
TI  - Uterine compression suture: not yet complete.

PMID- 24090464
TI  - Do we have guidelines for the prevention of Hepatitis B virus perinatal
      transmission?

PMID- 24090465
TI  - Abnormal P600 word repetition effect in elderly persons with preclinical
      Alzheimer's disease.
AB  - We sought cognitive event-related potential (ERP) biomarkers of "Preclinical
      Alzheimer's disease" (Pre-AD) using an incidental verbal learning paradigm with
      high sensitivity to prodromal AD. Seven elderly persons, with normal cognition at
      the time of ERP recordings, but who showed subsequent cognitive decline or AD
      pathology at autopsy (n = 5, mean Braak stage = 2.8), were compared to 12
      "robust" normal elderly (RNE) persons who remained cognitively normal (Mfollow-up
      = 9.0 years). EEG was recorded during a word repetition paradigm (semantically
      congruous (50%) and incongruous target words repeat ~10-140 seconds later). The
      RNE P600 congruous word repetition ERP effects (New minus Old congruous words)
      were significantly larger than in Pre-AD (mean amplitudes = 3.28 vs. 0.10 MUV, p
      = .04). High group discrimination (84%) was achieved (by a P600 amplitude cutoff
      of ~1.5 MUV). Abnormal P600 word repetition effects in cognitively normal elderly
      persons may be an important sign of synaptic dysfunction and Preclinical AD. 

PMID- 24090466
TI  - Isolation, characterization and comparative genomics of bacteriophage SfIV: a
      novel serotype converting phage from Shigella flexneri.
AB  - BACKGROUND: Shigella flexneri is the major cause of shigellosis in the developing
      countries. The O-antigen component of the lipopolysaccharide is one of the key
      virulence determinants required for the pathogenesis of S. flexneri. The
      glucosyltransferase and/or acetyltransferase genes responsible for the
      modification of the O-antigen are encoded by temperate serotype converting
      bacteriophage present in the S. flexneri genome. Several serotype converting
      phages have previously been isolated and characterized, however, attempts to
      isolate a serotype converting phage which encodes the modification genes of
      serotypes 4a strain have not been successful. RESULTS: In this study, a novel
      temperate serotype converting bacteriophage SfIV was isolated. Lysogenisation of
      phage SfIV converted serotype Y strain to serotype 4a. Electron microscopy
      indicated that SfIV belongs to Myoviridae family. The 39,758 bp genome of phage
      SfIV encompasses 54 open reading frames (orfs). Protein level comparison of SfIV
      with other serotype converting phages of S. flexneri revealed that SfIV is
      similar to phage SfII and SfV. The comparative analysis also revealed that SfIV
      phage contained five proteins which were not found in any other phages of S.
      flexneri. These proteins were: a tail fiber assembly protein, two hypothetical
      proteins with no clear function, and two other unknown proteins which were
      encoded by orfs present on a moron, that presumably got introduced in SfIV genome
      from another species via a transposon. These unique proteins of SfIV may play a
      role in the pathogenesis of the host. CONCLUSIONS: This study reports the
      isolation and complete genome sequence analysis of bacteriophage SfIV. The SfIV
      phage has a host range significantly different from the other phages of Shigella.
      Comparative genome analysis identified several proteins unique to SfIV, which may
      potentially be involved in the survival and pathogenesis of its host. These
      findings will further our understanding on the evolution of these phages, and
      will also facilitate studies on development of new phage vectors and therapeutic
      agents to control infections caused by S. flexneri.

PMID- 24090467
TI  - The survey on cellular and engineered tissue therapies in Europe in 2011.
AB  - Following the coordinated efforts of five established scientific organizations,
      this report describes the "novel cellular therapy" activity (i.e., cellular
      treatments excluding hematopoietic stem cells [HSC] for the reconstitution of
      hematopoiesis) in Europe for the year 2011. Two hundred forty-six teams from 35
      countries responded to the cellular therapy survey, 126 teams from 24 countries
      provided data on 1759 patients using a dedicated survey and 120 teams reported no
      activity. Indications were musculoskeletal/rheumatological disorders (46%; 99%
      autologous), cardiovascular disorders (22%; 100% autologous),
      hematology/oncology, predominantly including the prevention or treatment of graft
      versus-host disease (18%; 2% autologous), neurological disorders (2%; 83%
      autologous), gastrointestinal (1%; 68% autologous), and other indications (12%;
      77% autologous). Autologous cells were used predominantly for
      musculoskeletal/rheumatological (58%) and cardiovascular (27%) disorders, whereas
      allogeneic cells were used mainly for hematology/oncology (84%). The reported
      cell types were mesenchymal stem/stromal cells (56%), HSC (23%), chondrocytes
      (12%), dermal fibroblasts (3%), keratinocytes (2%), and others (4%). In 40% of
      the grafts, cells were delivered following ex vivo expansion, whereas cells were
      transduced or sorted, respectively, in 3% and 10% of the reported cases. Cells
      were delivered intraorgan (42%), intravenously (26%), on a membrane or gel (16%),
      or using 3D scaffolds (16%). Compared to last year, the number of teams
      participating in the dedicated survey doubled and, for the first time, all
      European Group for Blood and Marrow Transplantation teams reporting information
      on cellular therapies completed the extended questionnaire. The data are compared
      with those collected since 2008 to identify trends in the field. This year's
      edition specifically focuses on cardiac cell therapy. 

PMID- 24090468
TI  - Hierarchically porous nitrogen-doped graphene-NiCo(2)O(4) hybrid paper as an
      advanced electrocatalytic water-splitting material.
AB  - In this work, we report a three-dimensional (3D) oxygen evolution reaction (OER)
      catalyst with hierarchical pores for water splitting. The remarkable features of
      well-developed in- and out-of-plane pores, 3D conductive networks, and N-doping
      have greatly promoted the transport in electrodes and assured high catalytic
      efficiency. The 3D hybrid paper of N-doped graphene-NiCo2O4 has shown a
      remarkable OER catalytic activity that was comparable to that of previously
      reported noble metal catalysts (IrO2). The catalytic process occurred with
      favorable kinetics and strong durability. The dual-active-site mechanism is
      responsible for the excellent performance of the hybrid catalyst; that is, the
      edges of NiCo2O4 and the N (O)-metal (Ni or Co) bonds are both active sites. This
      study affords a new strategy to achieve optimal performance in 3D catalysts,
      which may be extended to the preparation of other 3D hybrid materials for a broad
      range of technological applications. 

PMID- 24090469
TI  - Identification of genetic contribution to ischemic stroke by screening of single
      nucleotide polymorphisms in stroke patients by using a case control study design.
AB  - BACKGROUND: Stroke is the second most common cause of death and disability
      worldwide. It is a multi-factorial disease influenced by both environmental and
      genetic factors. Studies from the different ethnic regions of world have reported
      variable results on association of Apolioprotein E (APOE),
      Methylenetetrahydrofolate reductase (MTHFR), Endothelial Nitric Oxide Synthase
      (ENOS), Factor V Leiden (F5), Cytochrome P450 4F2 (CYP4F2), beta-fibrinogen and
      Phosphodiesterase 4D (PDE4D) gene in stroke. There has been substantial evidence
      from the European descent genetic studies showing that genetic risk of stroke
      varies as per specific subtypes of ischemic stroke.This study aims to test the
      hypothesis that above mentioned encoding gene polymorphisms are associated with
      stroke and to determine whether risk varies as per specific subtypes of stroke.
      METHODS/DESIGN: The study design would be case-control study. Six hundred cases
      with diagnosis of stroke and 600 age and sex matched controls will be recruited.
      Controls will be matched in 1:1 ratio. Baseline and demographic data will be
      collected in standardized data collection form. Four ml of blood will be
      collected in EDTA coated vial and will be used for DNA isolation. Genotyping will
      be done by using PCR-RFLP method. For the reconfirmation of RFLP results, PCR
      product of each genotype in triplet for all the selected polymorphism will be
      sent for DNA sequencing. Data will be analyzed using conditional logistic
      regression to determine odds ratio associated with the above genes. DISCUSSION:
      This protocol will assess the association of above mentioned gene polymorphisms
      with ischemic stroke in North Indian Population. This study will also helpful to
      determine genetic component of stroke and whether variation in genetic risk as
      per different subtypes of stroke.

PMID- 24090470
TI  - Ambulation and complications related to assistive devices after spinal cord
      injury.
AB  - OBJECTIVE: To evaluate long-term health outcomes including pain intensity, pain
      interference, and fatigue among ambulatory persons with spinal cord injury (SCI).
      DESIGN: Prospective cohort study. SETTING: Data were analyzed at a major medical
      university in the southeast USA. PARTICIPANTS: Participants included 783
      ambulatory adults with SCI of traumatic origin, who were at least 1-year post
      injury. Participants were identified through three sources of records at a large
      specialty hospital in the southeastern USA. INTERVENTIONS: Not applicable.
      OUTCOME MEASURES: Pain intensity and interference (Brief Pain Inventory) and
      fatigue (Modified Fatigue Impact Scale Abbreviated Version 5). RESULTS: Examining
      assistive devices used for ambulation, 66% of the population used at least one
      device. In the logistic model, wheelchair and cane usage were significantly
      related to the outcomes after controlling for age, gender, and race. Wheelchair
      usage 50% of the time or less was significantly related to pain intensity (odds
      ratio (OR) 2.05, 95% confidence interval (CI) = 1.39-3.03), pain interference (OR
      2.11, 95% CI = 1.43-3.12), and fatigue (OR 1.99, 95% CI = 1.12-1.43).
      Additionally, unilateral cane use was significantly related to the outcomes; pain
      intensity (OR 1.86, 95% CI = 1.35-2.56), pain interference (OR 2.11, 95% CI =
      1.52-2.93), and fatigue (OR 2.49, 95% CI = 1.52-4.08). CONCLUSIONS: Among
      ambulatory persons with SCI, increased pain intensity, pain interference, and
      fatigue are associated with minimal wheelchair usage (50% or less) and less
      supportive assistive device (unilateral cane) usage.

PMID- 24090472
TI  - Hydrogen bond asymmetric local potentials in compressed ice.
AB  - A combination of the Lagrangian mechanics of oscillators vibration, molecular
      dynamics decomposition of volume evolution, and Raman spectroscopy of phonon
      relaxation has enabled us to resolve the asymmetric, local, and short-range
      potentials pertaining to the hydrogen bond (O:H-O) in compressed ice. Results
      show that both oxygen atoms in the O:H-O bond shift initially outwardly with
      respect to the coordination origin (H), lengthening the O-O distance by 0.0136 nm
      from 0.2597 to 0.2733 nm by Coulomb repulsion between electron pairs on adjacent
      oxygen atoms. Both oxygen atoms then move toward right along the O:H-O bond by
      different amounts upon being compressed, approaching identical length of 0.11 nm.
      The van der Waals potential VL(r) for the O:H noncovalent bond reaches a valley
      at -0.25 eV, and the lowest exchange VH(r) for the H-O polar-covalent bond is
      valued at -3.97 eV. 

PMID- 24090471
TI  - Circulating angiogenic biomolecules at rest and in response to upper-limb
      exercise in individuals with spinal cord injury.
AB  - OBJECTIVE: Individuals with spinal cord injury (SCI) show structural and
      functional vascular maladaptations and muscle loss in their lower limbs.
      Angiogenic biomolecules play important roles in physiological and pathological
      angiogenesis, and are implicated in the maintenance of muscle mass. This study
      examined the responses of angiogenic molecules during upper-limb aerobic exercise
      in patients with SCI and in able-bodied (AB) individuals. METHODS: Eight SCI
      patients with thoracic lesions (T6-T12, ASIA A) and eight AB individuals
      performed an arm-cranking exercise for 30 minutes at 60% of their VO2max. Plasma
      concentrations of vascular endothelial growth factor (VEGF-A165), VEGF receptor 1
      (sVEGFr-1), VEGF receptor 2 (sVEGFr-2), metalloproteinase 2 (MMP-2), and
      endostatin were measured at rest, after exercise, and at 1.5 and 3.0 hours during
      recovery. RESULTS: The two-way analysis of variance showed non-significant main
      effects of "group" and significant main effects of "time/exercise" for all
      angiogenic biomolecules examined (P < 0.01-0.001). The arm-cranking exercise
      significantly increased plasma concentrations of VEGF, sVEGFr-1, sVEGFr-2, MMP-2,
      and endostatin in both groups (P < 0.001-0.01). The magnitude of the increase was
      similar in both patients with SCI and AB individuals, as shown by the non
      significant group * time interaction for all angiogenic parameters. CONCLUSIONS:
      Upper-limb exercise (arm-cranking for 30 minutes at 60% of VO2max) is a
      sufficient stimulus to trigger a coordinated circulating angiogenic response in
      patients with SCI. The response of angiogenic molecules to upper-limb aerobic
      exercise in SCI appears relatively similar to that observed in AB individuals.

PMID- 24090473
TI  - Synthesis and molecular properties of four isomeric dialkylated angular-shaped
      naphthodithiophenes.
AB  - A new strategy to synthesize 4,9- and 5,10-dialkylated alpha-aNDTs as well as 4,9
      and 5,10-dialkylated beta-aNDTs is described. Four isomeric precursors with
      different dithienyl-ene-diyne arrangements undergo base-induced double 6pi
      cyclization to construct the central naphthalene cores, leading to the formation
      of the regiospecific products. These 2,7-distannylated dialkylated aNDT-based
      monomers can be used for Stille cross-coupling to produce promising conjugated
      materials for various optoelectronic applications. 

PMID- 24090474
TI  - Intractable hiccup caused by spinal cord lesions in demyelination disease.
AB  - OBJECTIVE: This study aimed to summarize the clinical features of patients who
      presented intractable hiccup (IH) without brain and medulla oblongata (MO)
      lesions. METHOD: This study included six patients who were diagnosed with
      inflammatory demyelinating myelitis, categorized as neuromyelitis optica (NMO),
      multiple sclerosis (MS), and myelitis. Patients who presented IH with cervical
      lesions but without MO lesions were also included. Clinical profiles, laboratory
      data, and magnetic resonance imaging findings were analyzed. RESULTS: Three out
      of six patients were diagnosed with NMO, whereas the remaining three were
      diagnosed with acute myelitis, recurrent myelities, and MS, respectively. The
      duration of hiccup was from 2 to 23 days (average = 9.33 +/- 8.64 days). Five
      patients (83.33%, patients 1-5) had long segmental lesions and one had a patchy
      lesion. None of these patients had any MO lesions. Half of them were successfully
      treated with high-dose methylprednisolone combined with gamma-aminobutyric acid
      (GABA) inhibitor. CONCLUSION: IH occurred in patients without MO lesion. However,
      the mechanism remained unclear. Immune factors of demyelinating neuropathy
      stimulated the hiccup reflex arch. Cervical cord lesions may activate the hiccup
      center. In general, IH can be controlled by IVMP combined with GABA inhibitor.
      Unilateral phrenic nerve block may elicit no effect.

PMID- 24090475
TI  - Biological noise abatement: coordinating the responses of autonomous bacteria in
      a synthetic biofilm to a fluctuating environment using a stochastic bistable
      switch.
AB  - Noise is inherent to single cell behavior. Its origins can be traced to the
      stochasticity associated with a few copies of genes and low concentrations of
      protein and ligands. We have studied the mechanisms by which the response of
      noisy elements can be entrained for biological signal processing. To elicit
      predictable biological function, we have engineered a gene environment that
      incorporates a gene regulatory network with the stringently controlled
      microenvironment found in a synthetic biofilm. The regulatory network leverages
      the positive feedback found in quorum-sensing regulatory components of the lux
      operon, which is used to coordinate cellular responses to environmental
      fluctuations. Accumulation of the Lux receptor in cells, resulting from
      autoregulation, confers a rapid response and enhanced sensitivity to the quorum
      sensing molecule that is retained after cell division as epigenetic memory. The
      memory of the system channels stochastic noise into a coordinated response among
      quorum-sensing signal receivers in a synthetic biofilm in which the noise
      diminishes with repeated exposure to noisy transmitters on the input of a
      signaling cascade integrated into the same biofilm. Thus, gene expression in the
      receivers, which are autonomous and do not communicate with each other, is
      synchronized to fluctuations in the environment. 

PMID- 24090478
TI  - Unilateral posterior cervical spinal cord infarction due to spontaneous vertebral
      artery dissection.
AB  - CONTEXT: Ischemia of the cervical spinal cord is a rare complication of
      spontaneous vertebral artery dissection (VAD) and usually involves the ventral
      portion. We describe a less evocative clinical presentation and images of
      unilateral posterior spinal cord infarction due to spontaneous VAD in order to
      facilitate early diagnosis. FINDINGS: A previously fit 30-year-old man presented
      with persistent headaches and proximal motor deficit of the right arm. He was
      diagnosed with spontaneous dissection of both vertebral arteries, with occlusion
      of the right one, and the right carotid artery. Neurological examination also
      revealed a right C2-C3 tactile sensory loss, with unilateral proprioceptive
      deficit below. Brain images revealed small bilateral cerebellar infarcts which
      could not be responsible for the clinical symptoms. Magnetic resonance imaging of
      the spinal cord showed a right posterior cervical spinal cord infarction. The
      patient achieved nearly complete recovery after several weeks of anticoagulation
      and rehabilitation. CONCLUSION AND CLINICAL RELEVANCE: Infarction of the caudal
      portion of the cervical spinal cord, especially unilateral, caused by spontaneous
      VAD, has rarely been described and is certainly under-diagnosed due to less
      suggestive symptoms, like unilateral and mainly sensory deficit. Nevertheless,
      early diagnosis of this condition is important to guide patient management and
      rehabilitation.

PMID- 24090476
TI  - Insights into soluble guanylyl cyclase activation derived from improved heme
      mimetics.
AB  - Recently, the structure of BAY 58-2667 bound to the Nostoc sp. H-NOX domain was
      published. On the basis of this structural information, we designed BAY 58-2667
      derivatives and tested their effects on soluble guanylyl cyclase (sGC) activity.
      Derivative 20 activated sGC 4.8-fold more than BAY 58-2667. Co-crystallization of
      20 with the Ns H-NOX domain revealed that the increased conformational distortion
      at the C-terminal region of alphaF helix containing 110-114 residues contributes
      to the higher activation triggered by 20. 

PMID- 24090479
TI  - Tumor angiogenesis genotyping and efficacy of first-line chemotherapy in
      metastatic gastric cancer patients.
AB  - AIM: Besides correlating with prognosis, tumor-driven angiogenesis also seemed
      able to influence response/resistance to chemotherapy in preclinical models. We
      examined the role of tumor angiogenesis genotyping in determining clinical
      outcome in metastatic gastric cancer patients receiving first-line chemotherapy.
      PATIENTS & METHODS: VEGF-A, VEGF-C, FLT1, KDR and FLT4 genotyping was analyzed in
      gastric tumors from patients receiving platinum-based first-line chemotherapy.
      RESULTS: VEGF-A rs25648 correlated with response rate (partial response: 18%
      among patients showing the VEGF-A rs25648 CT or TT genotype vs 44% among patients
      showing the VEGF-A rs25648 C genotype; p = 0.04). At multivariate analysis only
      VEGF-A rs25648 maintained an independent role in determining median progression
      free survival (hazard ratio: 1.65 95% CI: 1.12-2.78) and overall survival (hazard
      ratio: 1.58, 95% CI: 1.17-2.65). CONCLUSION: VEGF-A rs25648 genotyping may help
      identify a patient subgroup unlikely to benefit from a first-line, platinum-based
      combination and potential candidates for alternative therapy choices.

PMID- 24090480
TI  - Superior performance asymmetric supercapacitors based on a directly grown
      commercial mass 3D Co3O4@Ni(OH)2 core-shell electrode.
AB  - Pseudocapacitors based on fast surface Faradaic reactions can achieve high energy
      densities together with high power densities. Usually, researchers develop a thin
      layer of active materials to increase the energy density by enhancing the surface
      area; meanwhile, this sacrifices the mass loading. In this work, we developed a
      novel 3D core-shell Co3O4@Ni(OH)2 electrode that can provide high energy density
      with very high mass loading. Core-shell porous nanowires (Co3O4@Ni(OH)2) were
      directly grown on a Ni current collector as an integrated electrode/collector for
      the supercapacitor anode. This Co3O4@Ni(OH)2 core-shell nanoarchitectured
      electrode exhibits an ultrahigh areal capacitance of 15.83 F cm(-2). The
      asymmetric supercapacitor prototypes, assembled using Co3O4@Ni(OH)2 as the anode,
      reduced graphene oxide (RGO) or active carbon (AC) as the cathode, and 6 M
      aqueous KOH as the electrolyte, exhibit very high energy densities falling into
      the energy-density range of Li-ion batteries. Because of the large mass loading
      and high energy density, the prototypes can drive a minifan or light a bulb even
      though the size is very small. These results indicate that our asymmetric
      supercapacitors have outstanding potential in commercial applications. Systematic
      study and scientific understanding were carried out. 

PMID- 24090481
TI  - Implementation in Indonesia of the WHO Pocket Book of Hospital Care for Children.
AB  - BACKGROUND: Effective implementation of evidence-based practice guidelines has
      the potential to improve quality of hospital care for children. To achieve this
      in Indonesia, a locally adapted version of the WHO Pocket Book of Hospital Care
      for Children was published in 2009. OBJECTIVES: To document implementation of the
      Pocket Book in Indonesia and to compare uptake in health facilities in which
      there has been a quality-improvement approach involving audit and feedback with
      uptake in settings in which there has been only passive dissemination. METHODS:
      Indonesian district health offices, district hospitals, health centres with beds,
      and medical schools were surveyed by telephone, and an online and telephone
      survey of paediatricians was conducted. Health facilities in four provinces were
      visited, and key stakeholders were interviewed. Health facilities were assessed
      on availability of the guidelines, use by staff, and their incorporation into
      hospital procedures and activities. RESULTS: There was evidence of use of the
      Pocket Book across Indonesia, despite limited funding for implementation. Its
      distribution had reached all provinces; 61% (33/54) of health facilities surveyed
      had a copy of the guidelines. Hospitals involved in a related quality audit were
      more likely to report use of the guidelines than hospitals exposed to passive
      dissemination, although this difference was not significant. Of 150
      paediatricians sampled, 109 (73%) reported referring to the guidelines in their
      clinical practice. The guidelines have been incorporated into the postgraduate
      paediatric curriculum in four of 13 universities sampled. CONCLUSION: There was
      encouraging evidence of uptake of the Pocket Book in Indonesia following local
      adaptation, nationwide mailing distribution and small-scale local implementation
      activities.

PMID- 24090482
TI  - Antihyperglycemic and antihyperlipidemic activities of aqueous extract of
      Hericium erinaceus in experimental diabetic rats.
AB  - BACKGROUND: Hericium erinaceus, as a commonly used medicine or food, has
      attracted much attention due to its health effects when used as a home remedy for
      some diseases. The aim of this work was to investigate the hypoglycemic and
      hypolipidemic effects of aqueous extract of Hericium erinaceus (AEHE) in
      streptozotocin (STZ)-induced diabetic rats. METHODS: Diabetes was induced in
      Wistar rats by the administration of STZ (55 mg/kg BW.) intraperitoneally. AEHE
      (100 and 200 mg/kg BW.) was administered for a period of 28 days. The effects of
      AEHE on glucose, insulin, and lipid files in blood, and oxidative stress
      parameters in the liver were evaluated. The body weights of rats were recorded at
      day 0, 14 and 28th days. RESULTS: The administration of AEHE for 28 days in STZ
      diabetic rats resulted in a significant decrease in serum glucose level and a
      significant rise in serum insulin level. AEHE treatment attenuated lipid
      disorders. In addition, AEHE administration increased the activities of CAT, SOD,
      and GSH-Px, and GSH level, and reduced MDA level in the liver tissue
      significantly. CONCLUSION: Our results suggest that AEHE possesses hypoglycemic,
      hypolipidemic, and antioxidant properties in STZ-induced diabetes rats.

PMID- 24090483
TI  - Quantitative trait loci analysis reveals candidate genes implicated in regulating
      functional deficit and CNS vascular permeability in CD8 T cell-initiated blood
      brain barrier disruption.
AB  - BACKGROUND: Blood-brain barrier (BBB) disruption is an integral feature of
      numerous neurological disorders. However, there is a relative lack of knowledge
      regarding the underlying molecular mechanisms of immune-mediated BBB disruption.
      We have previously shown that CD8 T cells and perforin play critical roles in
      initiating altered permeability of the BBB in the peptide-induced fatal syndrome
      (PIFS) model developed by our laboratory. Additionally, despite having
      indistinguishable CD8 T cell responses, C57BL/6J (B6) mice are highly susceptible
      to PIFS, exhibiting functional motor deficits, increased astrocyte activation,
      and severe CNS vascular permeability, while 129S1/SvImJ (129S1) mice remain
      resistant. Therefore, to investigate the potential role of genetic factors, we
      performed a comprehensive genetic analysis of (B6 x 129S1) F2 progeny to define
      quantitative trait loci (QTL) linked to the phenotypic characteristics stated
      above that mediate CD8 T cell-initiated BBB disruption. RESULTS: Using single
      nucleotide polymorphism (SNP) markers and a 95% confidence interval, we
      identified one QTL (PIFS1) on chromosome 12 linked to deficits in motor function
      (SNP markers rs6292954, rs13481303, rs3655057, and rs13481324, LOD score = 3.3).
      In addition we identified a second QTL (PIFS2) on chromosome 17 linked to changes
      in CNS vascular permeability (SNP markers rs6196216 and rs3672065, LOD score =
      3.7). CONCLUSIONS: The QTL critical intervals discovered have allowed for
      compilation of a list of candidate genes implicated in regulating functional
      deficit and CNS vascular permeability. These genes encode for factors that may be
      potential targets for therapeutic approaches to treat disorders characterized by
      CD8 T cell-mediated BBB disruption.

PMID- 24090484
TI  - Measuring the impact of the Thoracolumbar Injury Classification and Severity
      Score among 458 consecutively treated patients.
AB  - CONTEXT: The Thoracolumbar Injury Classification and Severity Score (TLICS) was
      proposed to improve injury classification and guide surgical decision-making of
      thoracolumbar spinal trauma (TLST), but its impact on the care of patients has
      not been quantified. STUDY DESIGN: Retrospective study. PATIENT SAMPLE: Analysis
      of 458 patients treated for TLST trauma from 2000 through 2010 at a single
      center. Outcome measures Neurological status - ASIA Impairment Scale (AIS),
      failure of conservative treatment, and surgical complications. METHODS: Clinical
      and radiological data were evaluated. Patients were grouped according to the
      period before (2000-2006) and after (2007-2010) utilization of the TLICS.
      RESULTS: From 2000 to 2006, 148 patients were initially treated conservatively
      (C) and 66 were surgically (S) treated. In the C group, the TLICS ranged from 1
      to 7 (median 1; mean 1.57). In the S group, the TLICS ranged from 2 to 10 (median
      2; mean 4.14). The TLICS matched treatment in 97.9% of conservatively treated
      patients. From 2007 to 2010, 162 patients were initially treated C and 82 were
      treated S. In the C group, the TLICS ranged from 1 to 4 (median 1; mean 1.48). In
      the S group, the TLICS ranged from 2-10 (median 4; mean 4.4). The TLICS matched
      treatment in 98.8% of C-treated patients. Overall, failure of C treatment
      occurred in nine patients; most failures (7/9) and all three missed distractive
      injuries occurred prior to use of the TLICS. CONCLUSIONS: After introduction of
      the TLICS, there was a trend towards more successful conservative treatment with
      fewer conversions to surgical treatment.

PMID- 24090485
TI  - Reliability of robotic system during general surgical procedures in a university
      hospital.
AB  - BACKGROUND: Data concerning the reliability of robotic systems are scarce,
      especially for general surgery. The aim of this study was to assess the incidence
      and consequences of robotic malfunction in a teaching institution. METHODS: From
      January 2006 to September 2012, 526 consecutive robotic general surgical
      procedures were performed. All failures were prospectively recorded in a
      computerized database and reviewed retrospectively. RESULTS: Robotic malfunctions
      occurred in 18 cases (3.4%). These dysfunctions concerned the robotic instruments
      in 9 cases, the robotic arms in 4 cases, the surgical console in 3 cases, and the
      optical system in 2 cases. Two malfunctions were considered critical, and 1 led
      to a laparoscopic conversion (conversion rate due to malfunction, .2%). Overall,
      there were more dysfunctions at the beginning of the study period (2006 to 2010)
      than more recently (2011 to 2012) (4.2% vs 2.6%, P = .35). CONCLUSIONS: The
      robotic system malfunction rate was low. Most malfunctions could be resolved
      during surgery, allowing the procedures to be completed safely. With increased
      experience, the system malfunction rate seems to be reduced.

PMID- 24090486
TI  - Prevalence of psychiatric disorders in the first trimester of pregnancy and
      factors associated with current suicide risk.
AB  - This study aimed to describe the prevalence of psychiatric disorders and to
      identify the factors associated with Current Suicide Risk (CSR) in the first
      trimester of pregnancy. The Mini-International Neuropsychiatric Interview
      (M.I.N.I.) was employed to diagnose mental disorders in 239 women enrolled in a
      prospective cohort in Rio de Janeiro, Brazil. Serum lipids, leptin and socio
      economic status were the independent variables. CSR, the dependent variable, was
      entered as binary (yes/no) variable into crude and adjusted Poisson regression
      models with robust variances. CSR was found to be the main psychiatric syndrome
      (18.4%), followed by agoraphobia (17.2%), major depressive disorder (15.1%) and
      generalized anxiety disorder (10.5%). Women with CSR showed higher mean levels of
      cholesterol (169.2 vs. 159.2; p=0.017), high density lipoprotein (50.4 vs. 47.7;
      p=0.031) and low density lipoprotein (102.8 vs. 95.6; p=0.022) when compared to
      women without CSR. The adjusted regression model showed a higher prevalence ratio
      (PR) of CSR among pregnant women with generalized anxiety disorder (PR=2.70, 95%
      CI: 1.36-5.37), with >= two parturitions (PR=2.46, 95% CI: 1.22-4.93), and with
      major depressive disorder (PR=2.11, 95% CI: 1.08-4.12). We have shown that
      generalized anxiety disorder, major depressive disorder and higher parity are
      associated with CSR in the first trimester of pregnancy.

PMID- 24090487
TI  - The expression of excessive exercise co-segregates with the risk of developing an
      eating disorder in women.
AB  - Excessive exercise (EE) is an important symptom of eating disorders (ED) and is a
      likely risk factor for developing ED, however, no population-based studies have
      been performed on the relationship between EE and obtaining ED diagnosis. The aim
      of this study was to examine the co-occurrence of EE and ED diagnosis in a
      general population of women. Data for 778 females (age min=30, max=55) from the
      Saint Thomas Twin Registry, London were used. Phenotypes analyzed included self
      reported time spent on physical activity per week, ED diagnosis, Eating Disorder
      Inventory results (EDI-III), age, BMI and kinship (twin pair). Generalized
      Estimating Equation analysis showed that only EE (>5 h of exercise per week) and
      Bulimia Subscale of EDI-III were significantly associated with obtaining ED
      diagnosis throughout the life. These data revealed that the odds of ever being
      diagnosed with an ED are more than 2.5 times higher for excessive exercisers
      compared to individuals with lower activity levels. These data support the notion
      that EE may be an important risk factor for developing an ED in women.

PMID- 24090488
TI  - Transmission disequilibrium of DISC1 haplotypes in Bulgarian families with
      affective disorder.

PMID- 24090489
TI  - Controversies in preventive therapy for children contacts of multidrug-resistant
      tuberculosis.
AB  - BACKGROUND: Drug-resistant tuberculosis (DR-TB) is emerging as an increasing
      problem worldwide and no consensus has been reached about the management of
      children contacts of DR-TB cases. OBJECTIVE: To evaluate the role of post
      exposure chemoprophylaxis in paediatric DR-TB contacts, focusing on literature
      findings and recommendations from existing international guidelines. METHODS: We
      conducted a literature search of the Cochrane Library, MEDLINE by PubMed and
      EMBASE from database inception through September 2012, using an appropriate
      search strategy. RESULTS: Eighteen articles were included: four retrospective and
      two prospective population studies, eight international guidelines and four
      narrative reviews. CONCLUSIONS: General agreement exists that preventive therapy
      could be beneficial in specific high-risk groups, including immunocompromised
      children and those aged < 5 years. However, no consensus exists on the use of
      preventive therapy in older or immunocompetent children and on which regimen
      should be preferred.

PMID- 24090490
TI  - Longitudinal changes in medical complications in adults with pediatric-onset
      spinal cord injury.
AB  - OBJECTIVES: To determine longitudinal changes in the occurrence of medical
      complications in adults with pediatric-onset spinal cord injury (SCI). DESIGN:
      Longitudinal study of long-term outcomes. SETTING: Community. PARTICIPANTS:
      Individuals who had sustained an SCI before age 19, were 23 years of age or older
      at initial interview, and followed annually between 1996 and 2011. They were
      classified into four American Spinal Injury Association (ASIA) Impairment Scale
      (AIS) severity groups: C1-4 AIS ABC, C5-8 AIS ABC, T1-S5 AIS ABC, AIS D. OUTCOME
      MEASURES: Generalized estimating equation (GEE) models were formulated to obtain
      the odds ratio (OR) of having a medical complication over time. RESULTS: A total
      of 1793 interviews were conducted among 226 men and 125 women (86% Caucasian; age
      at baseline, 26.7 +/- 3.6 years; time since injury at baseline, 12.9 +/- 5.2
      years). Odds of complication occurrence over time varied among severity groups,
      with increased ORs of severe urinary tract infection (1.05, confidence interval
      (CI) 1.02-1.09), autonomic dysreflexia (AD) (1.09, CI 1.05-1.14), spasticity
      (1.06, CI 1.01-1.11), pneumonia/respiratory failure (1.09, CI 1.03-1.16), and
      hypertension/cardiac disease (1.07, CI 1.01-1.15) in the C1-4 ABC group; AD
      (1.08, CI 1.04-1.13) and pneumonia/respiratory failure (1.09, CI 1.02-1.16) in
      the C5-8 ABC group; and hypertension/cardiac disease (1.08, CI 1.02-1.14) in the
      T1-S5 ABC group. Upper extremity joint pain had increased odds of occurrence in
      all injury severity groups. CONCLUSION: The significantly increased odds of
      having medical complications over time warrants awareness of risk factors and
      implementation of preventive measures to avoid adverse consequences of
      complications and to maintain independence in individuals with pediatric-onset
      SCI.

PMID- 24090492
TI  - pH-mediated stoichiometric switching of cucurbit[8]uril-Hoechst-33258 complexes.
AB  - Stimuli-responsive molecular assemblies of potential drug/guest molecules through
      noncovalent host-guest interaction have been found very attractive in
      transporting and releasing the desired form on demand. In this article, the host
      guest interaction of a drug, Hoechst-33258 (H33258), has been investigated in
      aqueous solutions in the presence of a macrocyclic host, namely, cucurbit[8]uril
      (CB8). The pH dependent structural conformations of H33258 are found to be
      decisive in determining the stoichiometry and geometry of the supramolecular
      assembly. Interaction of CB8 with the monocationic H33258 at pH 7.2 is very
      strong with an overall binding constant of the order of 10(11) M(-2). The
      noncovalently stabilized assembly with 2:1 (CB8:H33258) stoichiometry brings out
      ~26-fold enhancement in the emission yield. On the other hand, the strong ion
      dipole interactions provided by the dicationic dye at pH 4.5 support the CB8 to
      uptake two dicationic H33258 dyes in its cavity in a 1:2 stoichiometry (K(pH 4.5)
      = (3.2 +/- 0.2) * 10(11) M(-2)). In this case, the fluorescence displayed a
      quenching with a decrease in the emission yield from 0.4 to 0.2. The distinct pH
      mediated stoichiometric switching of CB8-H33258 complexes and the contrasting
      fluorescence properties demonstrated here would find application in the field of
      biomolecular imaging and exchange of included guests for a selective drug
      transport/release. 

PMID- 24090491
TI  - Biomimetic protein nanoparticles facilitate enhanced dendritic cell activation
      and cross-presentation.
AB  - Many current cancer vaccine strategies suffer from the inability to mount a CD8 T
      cell response that is strong enough to overcome the low immunogenicity of tumors.
      Viruses naturally possess the sizes, geometries, and physical properties for
      which the immune system has evolved to recognize, and mimicking those properties
      with nanoparticles can produce robust platforms for vaccine design. Using the
      nonviral E2 core of pyruvate dehydrogenase, we have engineered a viral-mimicking
      vaccine platform capable of encapsulating dendritic cell (DC)-activating CpG
      molecules in an acid-releasable manner and displaying MHC I-restricted SIINFEKL
      peptide epitopes. Encapsulated CpG activated bone marrow-derived DCs at a 25-fold
      lower concentration in vitro when delivered with the E2 nanoparticle than with
      unbound CpG alone. Combining CpG and SIINFEKL within a single multifunctional
      particle induced ~3-fold greater SIINFEKL display on MHC I by DCs over unbound
      peptide. Importantly, combining CpG and SIINFEKL to the E2 nanoparticle for
      simultaneous temporal and spatial delivery to DCs showed increased and prolonged
      CD8 T cell activation, relative to free peptide or peptide-bound E2. By
      codelivering peptide epitopes and CpG activator in a particle of optimal DC
      uptake size, we demonstrate the ability of a noninfectious protein nanoparticle
      to mimic viral properties and facilitate enhanced DC activation and cross
      presentation. 

PMID- 24090493
TI  - Elastic properties of collagen in bone determined by measuring the Debye-Waller
      factor.
AB  - Force constant values for thermal vibrational motion of a collagen molecule along
      the helix axis in tendon, completely demineralized bone (CDB), and partially
      demineralized bone (PDB) were estimated by determining the Debye-Waller factor
      (DW factor) for the diffracted X-ray intensity from these specimens. The DW
      factor for nominal value of 0.286nm meridional diffraction representing a period
      along the helical axis of a collagen molecule was measured. As the atomic
      scattering factor of mineral constituents is much larger than that of collagen,
      it is difficult to detect the diffraction from collagen in bone specimen.
      Therefore, PDB was used in this study. In order to compare obtained force
      constant value for CDB with mechanical properties of collagen in the literature,
      the value was translated into Young's modulus value using the cross-sectional
      area of a collagen molecule. In the case of collagen in PDB, i.e., collagen with
      the close presence of HAp mineral particles, as the DW factor of the diffracted
      intensity by hydroxyapatite (HAp) was considered to be negligible compared with
      that of collagen, the DW factor determined was interpreted as that of collagen
      molecule in PDB specimen. The force constant value obtained for collagen in PDB
      was significantly larger than that of collagen in CDB. This result was thought to
      be a manifestation of the hardening of collagen matrix in bone by HAp mineral
      particles and the first straightforward evidence for a difference in collagen
      properties depending on the presence of HAp mineral particles. The method
      employed in this study can be utilized for detecting mechanical properties of the
      individual constituents of composite materials. 

PMID- 24090494
TI  - Acinus-on-a-chip: a microfluidic platform for pulmonary acinar flows.
AB  - Convective respiratory flows in the pulmonary acinus and their influence on the
      fate of inhaled particles are typically studied using computational fluid
      dynamics (CFD) or scaled-up experimental models. However, experiments that
      replicate several generations of the acinar tree while featuring cyclic wall
      motion have not yet been realized. Moreover, current experiments generally
      capture only flow dynamics, without inhaled particle dynamics, due to
      difficulties in simultaneously matching flow and particle dynamics. In an effort
      to overcome these limitations, we introduce a novel microfluidic device mimicking
      acinar flow characteristics directly at the alveolar scale. The model features an
      anatomically-inspired geometry that expands and contracts periodically with five
      dichotomously branching airway generations lined with alveolar-like cavities. We
      use micro-particle image velocimetry with a glycerol solution as the carrying
      fluid to quantitatively characterize detailed flow patterns within the device and
      reveal experimentally for the first time a gradual transition of alveolar flow
      patterns along the acinar tree from recirculating to radial streamlines, in
      support of hypothesized predictions from past CFD simulations. The current
      measurements show that our microfluidic system captures the underlying
      characteristics of the acinar flow environment, including Reynolds and Womersley
      numbers as well as cyclic wall displacements and alveolar flow patterns at a
      realistic length scale. With the use of air as the carrying fluid, our
      miniaturized platform is anticipated to capture both particle and flow dynamics
      and serve in the near future as a promising in vitro tool for investigating the
      mechanisms of particle deposition deep in the lung. 

PMID- 24090495
TI  - Stillbirth classification in population-based data and role of fetal growth
      restriction: the example of RECODE.
AB  - BACKGROUND: Stillbirth classifications use various strategies to synthesise
      information associated with fetal demise with the aim of identifying key causes
      for the death. RECODE is a hierarchical classification of death-related
      conditions, which grants a major place to fetal growth restriction (FGR). Our
      objective was to explore how placement of FGR in the hierarchy affected results
      from the classification. METHODS: In the Rhone-Alpes region, all stillbirths were
      recorded in a local registry from 2000 to 2010 in three districts (N = 969).
      Small for gestational age (SGA) was defined as a birthweight below the 10th
      percentile. We applied RECODE and then modified the hierarchy, including FGR as
      the penultimate category (RECODE-R). RESULTS: 49.0% of stillbirths were SGA. From
      RECODE to RECODE-R, stillbirths attributable to FGR decreased from 38% to 14%, in
      favour of other related conditions. Nearly half of SGA stillbirths (49%) were
      reclassified. There was a non-significant tendency toward moderate SGA,
      singletons and full-term stillbirths to older mothers being reclassified.
      CONCLUSIONS: The position of FGR in hierarchical stillbirth classification has a
      major impact on the first condition associated with stillbirth. RECODE-R calls
      less attention to monitoring SGA fetuses but illustrates the diversity of death
      related conditions for small fetuses.

PMID- 24090496
TI  - Patients with advanced Parkinson's disease with and without freezing of gait: a
      comparative analysis of vascular lesions using brain MRI.
AB  - INTRODUCTION: Freezing of gait (FOG) is one of the most disabling and enigmatic
      symptoms in Parkinson's disease. Vascular lesions, observed in magnetic resonance
      imaging (MRI) scans, may produce or exacerbate this symptom. PATIENTS AND
      METHODS: The study includes 22 patients with Parkinson's disease subjects, 12
      with freezing of gait and 10 without. All patients underwent an MRI scan and any
      vascular lesions were analysed using the modified Fazekas scale. RESULTS:
      Patients with FOG scored higher on the modified Fazekas scale than the rest of
      the group. Although the two groups contained the same percentage of patients with
      vascular lesions (50% in both groups), lesion load was higher in the group of
      patients with FOG. Vascular lesions in the periventricular area and deep white
      matter seem to be the most involved in the development of FOG. DISCUSSION:
      Vascular lesions may contribute to the onset or worsening of FOG in patients with
      PD. This study suggests that cerebral vascular disease should be considered in
      patients with FOG.

PMID- 24090497
TI  - Impact of climate and land use change on water availability and reservoir
      management: scenarios in the Upper Aragon River, Spanish Pyrenees.
AB  - Streamflows in a Mediterranean mountain basin in the central Spanish Pyrenees
      were projected under various climate and land use change scenarios. Streamflow
      series projected for 2021-2050 were used to simulate the management of the Yesa
      reservoir, which is critical to the downstream supply of irrigation and domestic
      water. Streamflows were simulated using the Regional Hydro-Ecologic Simulation
      System (RHESSys). The results show that increased forest cover in the basin could
      decrease annual streamflow by 16%, mainly in early spring, summer and autumn.
      Regional climate models (RCMs) project a trend of warming and drying in the basin
      for the period 2021-2050, which will cause a 13.8% decrease in annual streamflow,
      mainly in late spring and summer. The combined effects of forest regeneration and
      climate change are expected to reduce annual streamflows by 29.6%, with marked
      decreases affecting all months with the exception of January and February, when
      the decline will be moderate. Under these streamflow reduction scenarios it is
      expected that it will be difficult for the Yesa reservoir to meet the current
      water demand, based on its current storage capacity (476 hm(3)). If the current
      project to enlarge the reservoir to a capacity of 1059 hm(3) is completed, the
      potential to apply multi-annual streamflow management, which will increase the
      feasibility of maintaining the current water supply. However, under future
      climate and land cover scenarios, reservoir storage will rarely exceed half of
      the expected capacity, and the river flows downstream of the reservoir is
      projected to be dramatically reduced.

PMID- 24090498
TI  - Quality of life and female sexual function after skinning vulvectomy with split
      thickness skin graft in women with vulvar intraepithelial neoplasia or vulvar
      Paget disease.
AB  - OBJECTIVE: Vulvar intraepithelial neoplasia (VIN) and vulvar Paget disease are
      managed with either vulvectomy, destructive treatments (laser, antimitotic drugs)
      or immunostimulants. All these options are associated with functional
      complications. The purpose of this study was to evaluate the surgical technique
      consisting of skinning vulvectomy with split-thickness skin graft, and its effect
      on overall quality of life and sexual function. METHODS: A retrospective study
      was conducted on thirteen patients who underwent skinning vulvectomy with split
      thickness skin graft between 1999 and 2009. Overall quality of life and sexual
      function were assessed with the Medical Outcome Study Short Form 36 (MOS SF-36)
      and Female Sexual Function Index (FSFI), respectively. RESULTS: The median age of
      patients was 54 (range: 33-77) years. Three patients had Paget disease and 10
      patients had VIN lesions. The excision margins were clear in 46% of cases. The
      incidence of occult cancer was 31%. The mean follow-up period was 77 (+/-35)
      months. Four patients experienced a relapse of their intraepithelial disease. The
      mean disease-free survival was 58 (+/-44) months. There was no significant
      difference in MOS SF-36 scores between the study population and the general
      population. The patients assessed with the FSFI regained normal sexual function
      after the surgical procedure. CONCLUSION: Skinning vulvectomy with split
      thickness skin graft is a feasible technique yielding good results in terms of
      quality of life and sexual function. It enables occult cancer to be diagnosed in
      patients with VIN or Paget disease.

PMID- 24090499
TI  - InsertionMapper: a pipeline tool for the identification of targeted sequences
      from multidimensional high throughput sequencing data.
AB  - BACKGROUND: The advent of next-generation high-throughput technologies has
      revolutionized whole genome sequencing, yet some experiments require sequencing
      only of targeted regions of the genome from a very large number of samples. These
      regions can be amplified by PCR and sequenced by next-generation methods using a
      multidimensional pooling strategy. However, there is at present no available
      generalized tool for the computational analysis of target-enriched NGS data from
      multidimensional pools. RESULTS: Here we present InsertionMapper, a pipeline tool
      for the identification of targeted sequences from multidimensional high
      throughput sequencing data. InsertionMapper consists of four independently
      working modules: Data Preprocessing, Database Modeling, Dimension Deconvolution
      and Element Mapping. We illustrate InsertionMapper with an example from our
      project 'New reverse genetics resources for maize', which aims to sequence-index
      a collection of 15,000 independent insertion sites of the transposon Ds in maize.
      Identified sequences are validated by PCR assays. This pipeline tool is
      applicable to similar scenarios requiring analysis of the tremendous output of
      short reads produced in NGS sequencing experiments of targeted genome sequences.
      CONCLUSIONS: InsertionMapper is proven efficacious for the identification of
      target-enriched sequences from multidimensional high throughput sequencing data.
      With adjustable parameters and experiment configurations, this tool can save
      great computational effort to biologists interested in identifying their
      sequences of interest within the huge output of modern DNA sequencers.
      InsertionMapper is freely accessible at https://sourceforge.net/p/insertionmapper
      and http://bo.csam.montclair.edu/du/insertionmapper.

PMID- 24090500
TI  - Successful treatment of l-asparaginase-induced severe acute hepatotoxicity using
      mitochondrial cofactors.

PMID- 24090501
TI  - Early deaths in pediatric acute leukemia: a population-based study.
AB  - The purpose was to describe the incidence and risk factors associated with early
      deaths (<= 42 days from diagnosis) among children with acute lymphoblastic
      leukemia (ALL) and acute myeloid leukemia (AML) in Ontario, Canada. The data
      source for this population-based, retrospective cohort study was the Pediatric
      Oncology Group of Ontario Networked Information System (POGONIS). Patients with
      acute leukemia aged <= 18 years diagnosed between 1990 and 2010 were included.
      The study population consisted of 1954 children with ALL and 403 with AML. The
      early death rate was 40/2357 (1.7%), with 1.1% of patients with ALL and 4.7% of
      patients with AML dying early. Among all 442 deaths recorded, 9.0% occurred
      early. Twelve/40 (30.0%) early deaths were attributed to infection. Factors
      associated with early deaths were AML (p < 0.0001) and age >= 10 years at
      diagnosis (p = 0.038). Future interventions to improve survival may consider
      focusing on the early treatment period and may target AML and older patients.

PMID- 24090502
TI  - Medium-sized FLT3 internal tandem duplications confer worse prognosis than short
      and long duplications in a non-elderly acute myeloid leukemia cohort.
AB  - Internal tandem duplications (ITDs) of the fms-like tyrosine kinase 3 (FLT3) gene
      occur in about 25% of patients with adult acute myeloid leukemia (AML). The aim
      of our study was to investigate the frequency of FLT3-ITD mutations followed by a
      detailed analysis of the mutational load and size of ITD insertions in a cohort
      consisting of 324 patients younger than 60 years old and treated with curative
      intention. FLT3-ITD alone did not influence overall survival (OS) or disease-free
      survival (DFS). We observed worse OS and DFS for patients with high mutational
      load indicative for loss of the FLT3 wild type allele (p = 0.010, p = 0.038,
      respectively). In multivariate analyses, patients with FLT3-ITD(48-60bp) showed
      worse OS and DFS compared to other groups (FLT3-ITD(neg), FLT3-ITD (< 48b), FLT3
      ITD (> 60bp); p = 0.014, p = 0.019, respectively). Our novel observation
      suggested that not only high FLT3-ITD load, but also medium-sized ITD insertions
      (48-60 bp) represented an adverse prognostic subgroup of patients with AML.

PMID- 24090503
TI  - Plasma homocysteine, methionine and S-adenosylhomocysteine levels following high
      dose methotrexate treatment in pediatric patients with acute lymphoblastic
      leukemia or Burkitt lymphoma: association with hepatotoxicity.
AB  - This study aimed to investigate: (i) changes of plasma homocysteine, methionine
      and S-adenosylhomocysteine levels following high-dose methotrexate (HD-MTX)
      treatment and (ii) the correlation of these sulfur-containing amino acids with
      MTX-induced hepatotoxicity. Fifteen pediatric patients with acute lymphoblastic
      leukemia and one patient with Burkitt lymphoma, with a total of 26 treatment
      courses of HD-MTX, were enrolled. Homocysteine levels increased at 24 h after HD
      MTX treatment, and showed marginal decreases at 48 and 72 h. Methionine levels
      showed a biphasic pattern, i.e. an initial decrease at 24 h followed by increases
      at 48 and 72 h. S-adenosylhomocysteine exhibited a marginal decrease at 24 h.
      Changes of homocysteine exhibited significant correlation only with a maximum
      increase of alanine aminotransferase or total bilirubin from baseline. This study
      has demonstrated, for the first time, simultaneous changes of plasma
      homocysteine, methionine and S-adenosylhomocysteine following HD-MTX. The
      potential of homocysteine as a marker of hepatotoxicity is also presented.

PMID- 24090504
TI  - Epithelial-to-mesenchymal transition: what is the impact on breast cancer stem
      cells and drug resistance.
AB  - There is increasing interest in cancer stem cells (CSCs) and their role in cancer
      progression. Recently, CSCs have been identified in brain, skin, and intestinal
      tumors and it has been suggested that these CSCs are responsible for tumor growth
      and metastasis. In breast cancer fatality is often due to the development of
      metastatic disease (MBC). Almost 30% of early breast cancer patients eventually
      develop MBC and in 90% of these multi-drug resistance (MDR) occurs. This could be
      attributed to the presence of breast cancer stem cells (BCSCs). Epithelial-to
      mesenchymal transition (EMT) is a process known to contribute to metastasis in
      cancer and it is mainly characterized by loss of E-cadherin expression. The TGF
      beta signaling pathway has an established role in promoting EMT by down
      regulating E-cadherin via a number of transcription factors, such as Twist, Snail
      and Slug. EMT has also been reported to produce cells with stem cell-like
      properties. Definition of the exact molecular mechanisms that are involved in the
      generation of stem cells through EMT could lead to the identification of new
      potential therapeutic targets and enable the development of more efficient
      strategies for particular patient groups. In this review we discuss what is known
      about the relationship between EMT, BCSCs and MDR. 

PMID- 24090505
TI  - My epilepsy story: an interview with Gay Mitchell by Astrid Nehlig and Gary
      Mathern.

PMID- 24090506
TI  - Doppler flow parameters in orbital arteries in gestational diabetes mellitus
      patients.
AB  - OBJECTIVE: To evaluate the blood flow in orbital arteries in patients with
      gestational diabetes mellitus (GDM). MATERIAL: We have examined 65 GDM patients
      and 38 healthy pregnant women at 28-32 weeks. Doppler parameters were assessed in
      ophthalmic, central retinal and short posterior ciliary arteries. RESULTS: In
      ophthalmic arteries V2 was significantly higher and RI lower in GDM. In the
      subgroup treated with insulin V1 and V2 in ciliary artery and V2 in central
      retinal artery were significantly lower and PI in ciliary artery was higher when
      compared to subgroup on diet. CONCLUSION: Doppler examination can be useful in
      detection of pre-clinical ophthalmological changes in GDM patients.

PMID- 24090507
TI  - Clinicopathologic evaluation of salivary gland neoplasms: a 38-year retrospective
      study in Iran.
AB  - We present a 38-year retrospective study of 165 patients with salivary gland
      tumors that were diagnosed from 1971 to 2009 in the Department of Oral and
      Maxillofacial Pathology, Faculty of Dentistry, Mashhad, Iran. The histologic
      diagnoses were reevaluated according to the 2005 World Health Organization
      classification. A total of 165 tumors were identified in 79 male and 86 female
      patients. The mean age was 43.41 +/- 18.59 for male patients and 40.06 +/- 15.91
      for female patients. Although benign salivary gland tumors are usually more
      common than the malignant counterpart in previous studies, neoplasms showed an
      almost equal frequency of benign and malignant tumors in the present study. The
      frequency of major salivary gland tumors was 15.8%, and that of minor salivary
      gland tumors was 83%. The mean age of patients with major salivary gland tumors
      (44.30 years) was slightly higher than patients with minor ones (41.15 years).
      Pleomorphic adenoma was the most common histologic type of benign tumor
      identified, whereas mucoepidermoid was the most common malignant tumor. In
      contrast to some previous studies that have been reported parotid gland as the
      most common site for salivary tumors, in the current study, the palate was the
      most frequent location for salivary gland tumors and tumors have a propensity to
      occur at the palate than any other sites. Therefore, any lesion arising from the
      palate should be considered as a possible salivary gland tumor.

PMID- 24090508
TI  - Cementum-like matrix in solitary bone cysts: a unique and characteristic but yet
      underrecognized feature of promising diagnostic utility.
AB  - Solitary bone cysts (SBCs) are benign, intraosseus, cystic lesions, which
      generally involve metaphysis of long bones during the period of skeletal
      immaturity. Histologic features are nonspecific, but identification of amorphous
      cementum-like material provides a significant diagnostic clue. This material is
      unique to SBC with reported frequency of 10% to 70% and has been described as an
      immature form of bone. We retrieved and reviewed 41 cases of SBC reported in the
      last 10 years. The ages of patients ranged from 4 to 64 years (mean, 16 years),
      with a male-to-female ratio of 3:1. Humerus and femur were the most common sites.
      Cementum-like matrix was observed in 26 cases (63.4%). This material was seen in
      different phases of deposition and progression, ultimately transforming into
      mature bone as seen in 4 cases. Cyst wall lining was observed in 70.7% of cases
      along with several other nonspecific histologic features including reactive bone
      formation, hemosiderin macrophages, hemorrhage, multinucleated giant cells, foamy
      macrophages, fibrin, cholesterol clefts, and granulation tissue. Cementum-like
      material in the wall of SBCs is a specific and fairly consistent finding of
      diagnostic significance in cases where cyst wall lining is deficient. We also
      histologically demonstrate, for the first time, transformation of cementum-like
      material into reactive and mature bone, which further validates the immature
      osteoid nature and finding of other authors. 

PMID- 24090509
TI  - Expression of cell cycle and apoptosis-related proteins in ameloblastoma and
      keratocystic odontogenic tumor.
AB  - Tumors arising from epithelium of the odontogenic apparatus or from its
      derivatives or remnants exhibit considerable histologic variation and are
      classified into several benign and malignant entities. A high proliferative
      activity of the odontogenic epithelium in ameloblastoma (AM) and keratocystic
      odontogenic tumor (KCOT) has been demonstrated in some studies individually.
      However, very few previous studies have simultaneously evaluated cell
      proliferation and apoptotic indexes in AM and KCOT, comparing both lesions. The
      aim of this study was to assess and compare cell proliferation and apoptotic
      rates between these two tumors. Specimens of 15 solid AM and 15 KCOT were
      evaluated. The proliferation index (PI) was assessed by immunohistochemical
      detection of Ki-67 and the apoptotic index (AI) by methyl green-pyronin stain.
      KCOT presented a higher PI than AM (P < .05). No statistically significant
      difference was found in the AI between AM and KCOT. PI and AI were higher in the
      peripheral cells of AM and respectively in the suprabasal and superficial layers
      of KCOT. In conclusion, KCOT showed a higher cell proliferation than AM and the
      AI was similar between these tumors. These findings reinforce the classification
      of KCOT as an odontogenic tumor and should contribute to its aggressive clinical
      behavior.

PMID- 24090511
TI  - Electroconvulsive therapy increases hippocampal and amygdala volume in therapy
      refractory depression: a longitudinal pilot study.
AB  - Electroconvulsive therapy (ECT) is the most potent biological therapy in
      depression. Animal studies suggest that ECT acts via neuroplasticity effects on
      limbic structures involved in the pathophysiology of depression but in vivo
      evidence at the human system level is scarce. Therefore, the aim of the present
      study was to investigate the effect of ECT on hippocampus and amygdala volume in
      15 antidepressant-free patients with treatment refractory depression (seven
      males, range 42-63 years). ECT treatment was successful as indexed by a
      significant decrease in depressive symptoms (t14=13.6; p<0.001). Analysis of
      normalized volumetric data before and after ECT treatment revealed a significant
      volume increase of both hippocampus and amygdala (minimum p<0.005) with no
      evidence for a change in global brain volume. Though this change in volume cannot
      be clearly related to treatment effects, ECT is associated with broader
      neurotrophic effects other than mere adult neurogenesis in the hippocampus, which
      has been previously suggested as a core mechanism on the basis of animal data. 

PMID- 24090510
TI  - Regional homogeneity and resting state functional connectivity: associations with
      exposure to early life stress.
AB  - Early life stress (ELS) confers risk for psychiatric illness. Previous literature
      suggests ELS is associated with decreased resting-state functional connectivity
      (rs-FC) in adulthood, but there are no studies of resting-state neuronal activity
      in this population. This study investigated whether ELS-exposed individuals
      demonstrate resting-state activity patterns similar to those found in PTSD.
      Twenty-seven adults (14 with at least moderate ELS), who were medication-free and
      without psychiatric or medical illness, underwent MRI scans during two 4-minute
      rest periods. Resting-state activity was examined using regional homogeneity
      (ReHo), which estimates regional activation patterns through indices of localized
      concordance. ReHo values were compared between groups, followed by rs-FC analyses
      utilizing ReHo-localized areas as seeds to identify other involved regions.
      Relative to controls, ELS subjects demonstrated diminished ReHo in the inferior
      parietal lobule (IPL) and superior temporal gyrus (STG). ReHo values were
      inversely correlated with ELS severity. Secondary analyses revealed decreased rs
      FC between the IPL and right precuneus/posterior cingulate, left fusiform gyrus,
      cerebellum and caudate in ELS subjects. These findings indicate that ELS is
      associated with altered resting-state activity and connectivity in brain regions
      involved in trauma-related psychiatric disorders. Future studies are needed to
      evaluate whether these associations represent potential imaging biomarkers of
      stress exposure. 

PMID- 24090512
TI  - Eyeblink conditioning in unmedicated schizophrenia patients: a positron emission
      tomography study.
AB  - Previous studies suggest that patients with schizophrenia exhibit dysfunctions in
      a widely distributed circuit-the cortico-cerebellar-thalamic-cortical circuit, or
      CCTCC-and that this may explain the multiple cognitive deficits observed in the
      disorder. This study uses positron emission tomography (PET) with O(15) H2O to
      measure regional cerebral blood flow (rCBF) in response to a classic test of
      cerebellar function, the associative learning that occurs during eyeblink
      conditioning, in a sample of 20 unmedicated schizophrenia patients and 20 closely
      matched healthy controls. The PET paradigm examined three phases of acquisition
      and extinction (early, middle and late). The patients displayed impaired
      behavioral performance during both acquisition and extinction. The imaging data
      indicate that, compared to the control subjects, the patients displayed decreases
      in rCBF in all three components of the CCTCC during both acquisition and
      extinction. Specifically, patients had less rCBF in the middle and medial frontal
      lobes, anterior cerebellar lobules I/V and VI, as well as the thalamus during
      acquisition and although similar areas were found in the frontal lobe,
      ipsilateral cerebellar lobule IX showed consistently less activity in patients
      during extinction. Thus this study provides additional support for the hypothesis
      that patients with schizophrenia have a cognitive dysmetria--an inability to
      smoothly coordinate many different types of mental activity--that affects even a
      very basic cognitive task that taps into associative learning.

PMID- 24090513
TI  - Effect of "SOHAM" meditation on the human brain: an fMRI study.
AB  - The effect of "SOHAM" meditation has been investigated using functional magnetic
      resonance imaging (fMRI) in long-term meditators while they were meditating and
      not meditating. The results have revealed activation in left middle prefrontal
      cortex (MPFC) (Brodmann's area, BA 46), left inferior frontal gyrus (LIFG) (BA
      44), left supplementary motor area (SMA) (BA 6) and left precuneus (BA 5) during
      the meditation period compared to the control period (no-meditation period). The
      results have been interpreted in terms of regulation of the emotional state,
      attention and working memory of the meditators. 

PMID- 24090514
TI  - Relationships between the Arbeitsgemeinschaft fur Osteosynthesefragen Spine
      System and the Thoracolumbar Injury Classification System: an analysis of the
      literature.
AB  - CONTEXT: The Thoracolumbar Injury Classification System (TLICS) has been recently
      described to help surgeons in the decision-making process of thoracolumbar spinal
      trauma. OBJECTIVE: To analyze the potential relationships between the TLICS
      scores with the Arbeitsgemeinschaft fur Osteosynthesefragen (AO) Spine System and
      patient's neurological status. METHODS: Literature analysis of the potential
      scored injuries in the TLICS system, based on its individual scores, its total
      score, and its suggested proposed treatment, correlating these with the AO system
      and neurological status. RESULTS: Findings are presented according to the TLICS
      score. Patients with a TLICS 1-3 points, receiving conservative treatment, are AO
      type A injuries, generally neurologically intact. TLICS 4 group also included AO
      type A fractures, neurologically ranging from intact to complete spinal cord
      injury. TLICS 5-10 points includes AO type B and C injuries, regarding their
      neurological status, and burst fractures (AO type A) with concomitant
      neurological injury and most of the patients with incomplete deficits and cauda
      equina syndrome. CONCLUSIONS: As a general overview, according to the TLICS,
      patients without neurological deficit and with AO type A injuries are
      conservatively treated. AO type B and C injuries are managed surgically, with
      regard to neurological status. Patients with cauda equina or incomplete injuries
      also received a higher severity score. Controversies still exist regarding the
      management of unstable burst fractures without neurological status. The role of
      the posterior ligamentous complex status and the magnetic resonance imaging in
      the decision-making process require more clinical evidence.

PMID- 24090515
TI  - Use of indocyanine green videoangiography during intracranial aneurysm surgery
      reduces the incidence of postoperative ischaemic complications.
AB  - Microscope-integrated near-infrared indocyanine green videoangiography (ICGVA)
      has been shown to be a useful adjunct for intracranial aneurysm surgery. That the
      routine application of this technique reduces the risk of postoperative ischaemic
      complication, however, has not been reported. We present a retrospective matched
      pair comparison of ICGVA guided aneurysm surgery versus historic control surgical
      cohort treated by the same author. Index patients and controls were matched for
      aneurysm size, location, patient demographics, risk factors, comorbidities, and
      surgical treatments. Ninety-one eligible patients with 100 intracranial aneurysms
      were treated using ICGVA assistance. There were no statistically significant
      differences between the two groups in terms of patient age, sex, risk factors,
      comorbidities and aneurysm characteristics. Of the 100 aneurysms in the ICGVA
      group, 107 investigations of ICGVA were performed. In 79 aneurysms (79.0%), ICGVA
      was considered useful but did not affect surgical management. In six patients
      (6.0%), ICGVA led to a crucial change of intraoperative strategies. In nine
      patients (9.0%), it was considered critical in assuring patency of small
      perforators. ICGVA was of no benefit in four patients (4.0%) and was misleading
      in two (2.0%). Postoperative ischaemic complications occurred in three patients
      (3.3%) in the ICGVA group compared with seven patients (7.7%) in the control
      group (p<0.001). Our study supports the use of ICGVA in aneurysm surgery as a
      safe and effective modality of intraoperative blood flow assessment. With all
      limitations of a retrospective matched-pair comparison, the use of ICGVA during
      routine aneurysm surgery reduces the incidence of postoperative ischaemic
      complications. 

PMID- 24090516
TI  - Routine spinal navigation for thoraco-lumbar pedicle screw insertion using the O
      arm three-dimensional imaging system improves placement accuracy.
AB  - Modern image-guided spinal navigation employs high-quality intra-operative three
      dimensional (3D) images to improve the accuracy of spinal surgery. This study
      aimed to assess the accuracy of thoraco-lumbar pedicle screw insertion using the
      O-arm (Breakaway Imaging, LLC, Littleton, MA, USA) 3D imaging system. Ninety-two
      patients underwent insertion of thoraco-lumbar pedicle screws guided by O-arm
      navigation over a 27 month period. Intra-operative scans were retrospectively
      reviewed for pedicle breach. The operative time of patients where O-arm
      navigation was used was compared to a matched control group where fluoroscopy was
      used. A total of 467 pedicle screws were inserted. Four hundred and forty-five
      screws (95.3%) were placed within the pedicle without any breach (Gertzbein
      classification grade 0). Sixteen screws (3.4%) had a pedicle breach of less than
      2mm (Gertzbein classification grade 1), and six screws (1.3%) had a pedicle
      breach between 2mm and 4mm (Gertzbein classification grade 2). The grade 2 screws
      were revised intra-operatively. There was no incidence of neurovascular injury in
      this series of patients. The mean operative time for O-arm patients was 5.25
      hours. In a matched control group of fluoroscopy patients, the mean operative
      time was 4.75 hours. The difference in the mean operative time between the two
      groups was not statistically significant (p=0.15, paired t-test). Stereotactic
      navigation based on intra-operative O-arm 3D imaging resulted in high accuracy in
      thoraco-lumbar pedicle screw insertion.

PMID- 24090517
TI  - Dramatic response to intravenous immunoglobulins in dysautonomic
      neurosarcoidosis.

PMID- 24090518
TI  - The incidence, hospital expenditure, and, 30 day and 1 year mortality rates of
      spontaneous intracerebral hemorrhage in Taiwan.
AB  - The risks of morbidity and mortality are high in patients with spontaneous
      intracerebral hemorrhage (sICH). The medical care resources associated with sICH
      are also substantial. This study aimed to evaluate the medical expenditure for
      sICH patients in Taiwan. We analyzed the National Health Insurance Research
      Database from 2005 to 2010. The inclusion criterion was first-event sICH;
      traumatic ICH patients were excluded. Student's t-test, multiple linear
      regression and the chi-squared test were employed as the statistical methods. Our
      results showed that the incidence of sICH was 40.77 patients per 100,000 of
      population per year in Taiwan. The incidence increased with age and was greater
      in men than women. The mean hospital length of stay (LOS) of first-event sICH
      patients was 31.8 days; the mean LOS in the intensive care unit was 7.9 days; and
      the mean survival time was 60.4 months. The mortality rate within 30 days and
      within 1 year was 19.8 and 29.6%, respectively. The mean hospital expenditure of
      first-event sICH patients was USD $7572, and was highly correlated with LOS. In
      conclusion, the incidence of sICH in Taiwan is higher than that in white and
      black populations of northern America and some European countries and lower than
      that in the Asian populations of Japan and China. The features of male and female
      sICH patients differ. Our findings suggest that the hospital expenditure and
      mortality rate of sICH patients in Taiwan are comparable with those of other
      countries.

PMID- 24090519
TI  - Hippocampal-sparing radiotherapy: the new standard of care for World Health
      Organization grade II and III gliomas?
AB  - The neurocognitive effects of cranial radiotherapy in patients with gliomas are
      well-recognised and may be related to the dose delivered to the hippocampi.
      Intensity modulated radiotherapy (IMRT) is a radiotherapy technique that can be
      used to selectively spare the hippocampi without compromising the dose delivered
      to the tumour. This study aimed to evaluate if hippocampal-sparing IMRT is
      achievable in patients with World Health Organization (WHO) grade II and III
      gliomas. A retrospective review of consecutive patients with WHO grade II and III
      gliomas treated with IMRT at our institution between January 2009 and August 2012
      was performed. Hippocampal-sparing was defined as a mean dose to at least one
      hippocampus of less than 30 Gy. The dose delivered to the tumour was never
      compromised to achieve the hippocampal dose constraint. Logistic regression
      analyses were performed to identify predictive factors for achieving hippocampal
      sparing treatment. Eighteen patients were identified and hippocampal-sparing was
      achieved in 14 (78%). The median dose prescribed was 59.4 Gy in 33 fractions and
      11 patients had WHO grade III gliomas. The mean dose to the contralateral
      hippocampus was 24.9 Gy. Planning target volumes less than 420.5 cm3 were more
      likely to enable hippocampal-sparing treatment to be given (hazard ratio 1.7,
      p=0.03) and there was a trend with oligodendrogliomas and anaplastic
      oligodendrogliomas. Hippocampal-sparing radiotherapy is feasible in patients with
      WHO grade II and III gliomas. Oncologic outcomes are yet to be assessed
      prospectively. The relationship between hippocampal dose and neurocognitive
      function in adults is currently under investigation.

PMID- 24090520
TI  - Placement of a subdural evacuating port system for management of iatrogenic
      hyperacute subdural hemorrhage following intracranial monitor placement.
AB  - A 22-year-old man was admitted with a severe traumatic brain injury developed a
      hyperacute subdural hematoma (SDH) following attempted brain tissue oxygen
      monitor placement. This patient was successfully treated by placement of a
      subdural evacuation portal system (SEPS). The patient presented to a Level I
      trauma center after a severe bike versus auto accident. On admission, he was
      found to have a Glasgow Coma Scale (GCS) score of 3. The patient had small areas
      of intraparechymal hemorrhage as well as suspicion for diffuse axonal injury in
      the midbrain. Based on the patient's GCS score, neurological monitoring was
      indicated as a part of his intensive care unit treatment, however a SDH occurred
      during an attempted placement of a brain tissue oxygen monitor. This iatrogenic
      hyperacute SDH after burr hole monitoring device placement was treated with a
      SEPS drain. The SEPS drain has been shown to provide complete and/or temporary
      decompression of liquefied SDH. To our knowledge, this is the first report of
      using the SEPS to treat iatrogenic SDH associated with an intracranial monitoring
      device. This technique should be added to the armament of treatment options for a
      neurosurgeon to treat or temporize a hyperacute SDH with increased intracranial
      pressure in specific patients. 

PMID- 24090521
TI  - [Factors associated with early weaning in a Spanish region].
AB  - INTRODUCTION: Breastfeeding has undoubtedly great benefits. Previous studies have
      foundan early dropout. Only a few studies have investigated related factors. Our
      aim was to find out on-going breastfeeding rates along the first 12 months after
      birth and analyse factors associated with early weaning. MATERIAL AND METHODS:
      This is a prospective study including consecutive pairs (mother and newborn) till
      completion of the required sample. Variables were collected performing a
      structured program of surveys to the mothers. Bivariate and multivariate analysis
      of the data was performed. RESULTS: A total of 452 pairs were recruited. It was
      found that 81% of them started breastfeeding, with a prevalence of breastfeeding
      of 39% and 21% at 3 and 6 months after birth, respectively. Factors associated
      with early discontinuation of breastfeeding were: pregnancy induced by assisted
      reproduction methods (OR=5.58; 95% CI: 2.62-11.91), maternal smoking (OR=1.56;
      95% CI: 1.10-2.22), poor maternal expectations about the duration of
      breastfeeding (OR=2.19; 95% CI: 1.49-3.23), use of nipple shields for
      breastfeeding (OR=2.57; 95% CI: 1.69-3.90), pacifier use on a regular basis
      during the first month after delivery (OR=1.39; 95% CI: 1.02-1.91), maternal
      university educational level (OR=0,59; 95% CI: 0,40-0,88), attending birth
      preparation programs during pregnancy (OR=0,68; 95% CI: 0,49-0,94), and believing
      having enough milk output at the time of discharge (OR=0,66; 95% CI: 0,47-0,92).
      CONCLUSIONS: International recommendations about duration of breastfeeding are
      not achieved in our country because of high rates of early weaning. We describe
      the known factors involved and other novel factors. The implementation of
      interventions to increase breastfeeding rates and to prevent early weaning are
      strongly recommended.

PMID- 24090522
TI  - For us or against us? Perceptions of faculty bullying of students during
      undergraduate nursing education clinical experiences.
AB  - The purpose of this review is to determine what we currently know about faculty
      bullying of nursing students during undergraduate clinical experiences. The
      review included 31 peer-reviewed articles and dissertations investigating faculty
      bullying of nursing students and those factors which can influence the
      phenomenon. A significant finding of this review is that faculty bullying of
      students arises out of complex contextual influences involving the practice
      setting, as well as perceptions and coping strategies of both faculty members and
      students. This belies the current understanding of bullying within nursing
      education as intentional, and arising from the personal pathologies of the
      teacher or student. This has implications for clinical faculty members as well as
      Schools of Nursing. As well, it highlights future directions for research,
      including interventions to decrease faculty bullying of students.

PMID- 24090523
TI  - Electronic portfolios in nursing education: a review of the literature.
AB  - As health professionals, nurses are responsible for staying abreast of current
      professional knowledge and managing their own career, professional growth and
      development, and ideally, practices to support these activities should start
      during their student years. Interest in electronic or eportfolios is gathering
      momentum as educationalists explore their potential as a strategy for fostering
      lifelong learning and enhancing on-going personal and professional development.
      In this paper, we present an overview of e-portfolios and their application to
      nurse education, highlighting potential benefits and considerations of useage. We
      argue that the e-portfolio can represent an authentic means of assessing
      cognitive, reflective and affective skills. Furthermore, the e-portfolio provides
      a means through which nurses can record and provide evidence of skills,
      achievements, experience, professional development and on-going learning, not
      only for themselves, but for the information and scrutiny of registration boards,
      employers, managers and peers. 

PMID- 24090524
TI  - Long-term follow-up of spinal cord stimulation to restore cough in subjects with
      spinal cord injury.
AB  - OBJECTIVE: To determine the long-term effects of the cough stimulation system.
      DESIGN: Nonrandomized clinical trial of subjects using the study device well
      beyond the period of close follow-up. SETTING: Use of the study device in the
      home setting. PARTICIPANTS: Subjects (N = 10) implanted with the device for a
      minimum of 2 years (mean 4.6 +/- 0.6 years). INTERVENTIONS: Application of daily
      stimulation. OUTCOME MEASURES: Airway pressure generation and other clinical
      assessments including ease in raising secretions, life quality, caregiver
      support, and incidence of respiratory tract infections were measured at 1 year
      and mean 4.6 years after implantation. RESULTS: Each subject continued to use the
      device on a regular basis. During SCS, mean maximum airway pressures were 103.1
      +/- 20.4 and 107.7 +/- 23.0 cm H2O at the 1-year and mean 4.6-year follow-up
      points, respectively (P < 0.05 compared with pre-implant and not significantly
      different (NS) compared with 1-year follow-up). Benchmarks related to ease in
      raising secretions and improvements in life quality related to respiratory care
      were maintained at the mean 4.6 year follow-up. The need for trained caregivers
      to provide other means of secretion management remained significantly below the
      pre-implant values (P < 0.05). The incidence of acute respiratory tract
      infections remained low at 0.2 +/- 0.1 events/year, which is significantly below
      the pre-implant value of 1.4 +/- 0.3 events/year (P < 0.05). CONCLUSION: Subjects
      continued to use the system on a long-term basis beyond the period of close
      follow-up and to continued derive significant clinical benefits.

PMID- 24090525
TI  - Severe heart failure, dilated cardiomyopathy and pulmonary haemosiderosis in
      coeliac disease: report of two cases.
AB  - Coeliac disease (CD) is a chronic inflammatory, multi-system disorder with
      protean manifestations which has been linked to various auto-immune-mediated
      disorders. Dilated cardiomyopathy (DCM) is a rare extra-intestinal manifestation
      that is being recognised increasingly in patients with CD. Two cases of CD are
      described, an 18-year-old boy and a 13-year-old girl, both of whom presented with
      rapid onset of congestive heart failure and severe left ventricular systolic
      dysfunction. Upper limb venous thrombosis and recurrent haemoptysis secondary to
      pulmonary haemosiderosis in the second case were the other unusual features. The
      importance of CD screening of patients with DCM and pulmonary haemosiderosis is
      emphasised. 

PMID- 24090526
TI  - A new look at the infrared spectrum of the weakly bound CO-N2 complex.
AB  - A broad-band (2135-2165 cm(-1)) infrared spectrum of the CO-N2 van der Waals
      complex is obtained, using a tunable quantum cascade laser to probe a pulsed
      supersonic expansion from a slit jet source. Analysis of the spectrum results in
      the characterization of four new 'stacks' of rotational levels for CO-orthoN2
      (all in the v(CO) = 1 upper state) and five new stacks for CO-paraN2 (three in
      the upper state and two in the vCO = 0 lower state). This considerably expands
      our knowledge of a rather fundamental weakly bound complex and should lead to
      improved determinations of the intermolecular forces governing interactions
      between the carbon monoxide and nitrogen molecules.

PMID- 24090527
TI  - Pharmacodynamic target attainment with high-dose extended-interval tobramycin
      therapy in patients with cystic fibrosis.
AB  - Utilization of high-dose extended-interval aminoglycoside therapy (HEAT) in
      patients with cystic fibrosis (CF) is supported by primary literature and
      national guidelines. We sought to evaluate the effectiveness of a local
      aminoglycoside guideline to achieve pharmacodynamic goals in patients with CF
      that received ?3 doses of HEAT from 2005 to 2011. Patients with renal dysfunction
      at baseline, status-post-lung transplant, or receiving inhaled tobramycin were
      excluded. In the 282 patient admissions, the average initial tobramycin dose was
      10.3 mg/kg with an average initial peak of 21.5 mg/l. At least one dose titration
      was seen in 39% of patients. Patients who achieved the pharmacodynamic goal
      received a higher dose (10.4 mg/kg versus 9.7 mg/kg; P<0.001). A mean starting
      dose of tobramycin at 10.3 mg/kg every 24 hours achieved an average peak above
      goal. Higher initial dosing resulted in a higher likelihood of achieving the
      pharmacodynamic goal. 

PMID- 24090528
TI  - Metal-enhanced fluorescence platforms based on plasmonic ordered copper arrays:
      wavelength dependence of quenching and enhancement effects.
AB  - Ordered arrays of copper nanostructures were fabricated and modified with
      porphyrin molecules in order to evaluate fluorescence enhancement due to the
      localized surface plasmon resonance. The nanostructures were prepared by
      thermally depositing copper on the upper hemispheres of two-dimensional silica
      colloidal crystals. The wavelength at which the surface plasmon resonance of the
      nanostructures was generated was tuned to a longer wavelength than the interband
      transition region of copper (>590 nm) by controlling the diameter of the
      underlying silica particles. Immobilization of porphyrin monolayers onto the
      nanostructures was achieved via self-assembly of 16-mercaptohexadecanoic acid,
      which also suppressed the oxidation of the copper surface. The maximum
      fluorescence enhancement of porphyrin by a factor of 89.2 was achieved as
      compared with that on a planar Cu plate (CuP) due to the generation of the
      surface plasmon resonance. Furthermore, it was found that while the fluorescence
      from the porphyrin was quenched within the interband transition region, it was
      efficiently enhanced at longer wavelengths. It was demonstrated that the
      enhancement induced by the proximity of the fluorophore to the nanostructures was
      enough to overcome the highly efficient quenching effects of the metal. From
      these results, it is speculated that the surface plasmon resonance of copper has
      tremendous potential for practical use as high functional plasmonic sensor and
      devices. 

PMID- 24090529
TI  - The usual treatment of trigeminal autonomic cephalalgias.
AB  - Trigeminal autonomic cephalalgias include cluster headache, paroxysmal
      hemicrania, and short-lasting unilateral neuralgiform headache attacks with
      conjunctival injection, tearing, and rhinorrhea (SUNCT). Conventional
      pharmacological therapy can be successful in the majority of trigeminal autonomic
      cephalalgias patients. Most cluster headache attacks respond to 100% oxygen
      inhalation, or 6 mg subcutaneous sumatriptan. Nasal spray of sumatriptan (20 mg)
      or zolmitriptan (5 mg) are recommended as second choice. The bouts can be brought
      under control by a short course of corticosteroids (oral prednisone: 60-100
      mg/day, or intravenous methylprednisolone: 250-500 mg/day, for 5 days, followed
      by tapering off the dosage), or by long-term prophylaxis with verapamil (at least
      240 mg/day). Alternative long-term preventive medications include lithium
      carbonate (800-1600 mg/day), methylergonovine (0.4-1.2 mg/day), and topiramate
      (100-200 mg/day). As a rule, paroxysmal hemicrania responds to preventive
      treatment with indomethacin (75-150 mg/day). A short course of intravenous
      lidocaine (1-4 mg/kg/hour) can reduce the flow of attacks during exacerbations of
      SUNCT. Lamotrigine (100-300 mg/day) is the preventive drug of choice for SUNCT.
      Gabapentin (800-2700 mg/day), topiramate (50-300 mg/day), and carbamazepine (200
      1600 mg/day) may be of help. 

PMID- 24090530
TI  - Diagnosis and clinical features of trigemino-autonomic headaches.
AB  - Although severe short-lasting headaches are rare, they can be considered
      disabling conditions with a major impact on the quality of life of patients.
      These headaches can divided broadly in to those associated with autonomic
      symptoms, so called trigeminal autonomic cephalgias (TACs), and those with few or
      no autonomic symptoms. The TACs include cluster headache, paroxysmal hemicranias,
      hemicrania continua, and short-lasting unilateral neuralgiform headache attacks
      with cranial autonomic symptoms as well as short-lasting unilateral neuralgiform
      headache attacks with conjunctival injection and tearing syndrome. In all of
      these syndromes, half-sided head pain and ipsilateral cranial autonomic symptoms
      such as lacrimation or rhinorrhea are prominent. The paroxysmal hemicranias have,
      unlike cluster headaches, a very robust response to indomethacin, leading to a
      notion of indomethacin-sensitive headaches. The diagnosis of TACs is exclusively
      a clinical task. Because of the fact that cluster headache is strictly half
      sided, typically involves the region around the eye and temple and often starts
      in the upper jaw, most patients first consult a dentist or ophthalmologist. No
      single instrumental examination has yet been able to define, or ensure, the
      correct diagnosis, or differentiate idiopathic headache syndromes. It is crucial
      that a trained neurologist sees these patients early so that management can be
      optimized and unnecessary procedures can be avoided. Although TACS are, in
      comparison to migraine, quite rare, they are nevertheless clinically very
      important for the neurologist to consider as they are easy to diagnose and the
      treatment is very effective in most patients. 

PMID- 24090531
TI  - Expert commentary.

PMID- 24090533
TI  - Editorial: traumatic brain injury (TBI), pain, and headache.

PMID- 24090535
TI  - [Magnesium].

PMID- 24090536
TI  - Clinical pharmacology of carbapenems in neonates.
AB  - Carbapenems are an effective tool to treat complicated bacterial infections. This
      review aims to summarize the available information on carbapenems in neonates to
      guide clinicians on drug choice and indications in neonates. Moreover,
      identification of knowledge gaps may stimulate researchers to design studies to
      further improve pharmacotherapy in neonates. To do so, a bibliographic search
      [infant/newborn and meropenem, imipenem, panipenem, ertapenem, doripenem or
      imipenem] was performed (PubMed, EMBASE) and public clinical trial registries
      (clinicaltrials.gov, EU registry) were searched to summarize the available
      information. Carbapenem clearance in neonates is low. Variability relates to
      maturation (weight, age) and renal function (creatinine clearance), while
      observations in neonates with renal failure are absent. Pharmacodynamics are
      almost exclusively limited to meropenem, and the available information will
      further increase (NeoMero-1-2, necrotizing enterocolitis, meningitis). Finally,
      there are also some ongoing doripenem pharmacokinetics (PK) studies in neonates.
      It was concluded that observations on carbapenems in neonates are limited, but
      studies (NeoMero, doripenem) are ongoing. Until this information becomes
      available, off label prescription of meropenem seems to be the most reasonable
      choice when a carbapenem is appropriate. Knowledge gaps relate to PK in neonates
      with renal failure and to the potential benefit of prolonged compared to short
      duration of infusion. 

PMID- 24090534
TI  - Traumatic brain injury, neuroinflammation, and post-traumatic headaches.
AB  - Concussions following head and/or neck injury are common, and although most
      people with mild injuries recover uneventfully, a subset of individuals develop
      persistent post-concussive symptoms that often include headaches. Post-traumatic
      headaches vary in presentation and may progress to become chronic and in some
      cases debilitating. Little is known about the pathogenesis of post-traumatic
      headaches, although shared pathophysiology with that of the brain injury is
      suspected. Following primary injury to brain tissues, inflammation rapidly
      ensues; while this inflammatory response initially provides a
      defensive/reparative function, it can persist beyond its beneficial effect,
      potentially leading to secondary injuries because of alterations in neuronal
      excitability, axonal integrity, central processing, and other changes. These
      changes may account for the neurological symptoms often observed after traumatic
      brain injury, including headaches. This review considers selected aspects of the
      inflammatory response following traumatic brain injury, with an emphasis on the
      role of glial cells as mediators of maladaptive post-traumatic inflammation. 

PMID- 24090537
TI  - Measurement of food reinforcement in preschool children. Associations with food
      intake, BMI, and reward sensitivity.
AB  - Progressive ratio (PR) schedules of reinforcement have been used to measure the
      relative reinforcing value (RRV) of food in humans as young as 8 years old;
      however, developmentally appropriate measures are needed to measure RRV of food
      earlier in life. Study objectives were to demonstrate the validity of the RRV of
      food task adapted for use among for preschool children (3-5 y), and examine
      individual differences in performance. Thirty-three children completed the RRV of
      food task in which they worked to access graham crackers. They also completed a
      snack task where they had free access these foods, liking and hunger assessments,
      and their heights and weights were measured. Parents reported on their child's
      reward sensitivity. Overall, children were willing work for palatable snack
      foods. Boys and older children made more responses in the task, while children
      with higher BMI z-scores and reward sensitivity responded at a faster rate.
      Children who worked harder in terms of total responses and response rates
      consumed more calories in the snack session. This study demonstrates that with
      slight modifications, the RRV of food task is a valid and developmentally
      appropriate measure for assessing individual differences in food reinforcement
      among very young children.

PMID- 24090538
TI  - Implementing a patient education intervention about Methicillin-resistant
      Staphylococcus aureus prevention and effect on knowledge and behavior in veterans
      with spinal cord injuries and disorders: a pilot randomized controlled trial.
AB  - OBJECTIVES: To assess the feasibility and effect of a nurse-administered patient
      educational intervention about Methicillin-resistant Staphylococcus aureus (MRSA)
      prevention on knowledge and behavior of Veterans with spinal cord injuries and
      disorders (SCI/D). DESIGN: Blinded, block-randomized controlled pilot trial.
      SETTING: Two Department of Veterans Affairs (VA) SCI Centers. PARTICIPANTS:
      Veterans were recruited March-September 2010 through referral by a healthcare
      provider from inpatient, outpatient, and residential care settings. INTERVENTION:
      Thirty participants were randomized to the nurse-administered intervention and 31
      to the usual care group. The intervention included a brochure and tools to assist
      nurses in conducting the education. OUTCOME MEASURES: Pre- and post-intervention
      measurement of knowledge and behaviors related to MRSA and prevention strategies
      and feasibility measures related to implementation. RESULTS: Participants were
      primarily male (95.1%), white (63.9%), with tetraplegia (63.9%) and mean age and
      duration of injury of 64.3 and 20.5 years, respectively. The intervention groups
      mean knowledge score significantly increased between pre- and post-test (mean
      change score = 1.70, 95% confidence interval, CI 0.25-3.15) while the usual care
      groups score did not significantly change (mean change score = 1.45, 95% CI -0.08
      2.98). However, the mean knowledge change between intervention and usual care
      groups was not significantly different (P = 0.81). Overall behavior scores did
      not significantly differ between treatment groups; however, the intervention
      group was more likely to report intentions to clean hands (90.0% vs. 64.5%, P =
      0.03) and asking providers about MRSA status (46.7% vs. 16.1%, P = 0.01). Nurse
      educators reported that the quality of the intervention was high and could be
      implemented in clinical care. CONCLUSIONS: A targeted educational strategy is
      feasible to implement in SCI/D clinical practices and may improve some
      participants' knowledge about MRSA and increase intentions to improve hand
      hygiene and engagement with providers about their MRSA status.

PMID- 24090539
TI  - Clinical results of patients with subaxial cervical spine trauma treated
      according to the SLIC score.
AB  - OBJECTIVE: The Subaxial Injury Classification (SLIC) system has been developed to
      improve injury classification and guide surgical decision making yet clinical
      validation remains necessary. METHODS: We evaluated the validity and safety of
      the SLIC system prospectively in patients treated for subaxial cervical spine
      trauma (SCST) between 2009 and 2012. Patients with four or more points were
      surgically treated, whereas patients with less than 4 points were conservatively
      managed. OUTCOME MEASURES: Neurological status was assessed as the primary
      outcome of successful treatment. RESULTS: Non-surgical group - Twenty-three
      patients were treated non-surgically, 14 (61%) of them with some follow-up at our
      institution. Follow-up ranged from 3 to 5 months (mean of 4.42; median 4). The
      SLIC score ranged from 0 to 6 points (mean and median of 1). One patient with a
      SLIC of 6 points refused surgery. Surgical group: Twenty-five patients were
      operated, but follow-up after hospital discharge was obtained in 23 (92%)
      patients (range from 1 to 24 months, mean of 5.82 months). The SLIC score in this
      group ranged from 4 to 9 points (mean and median of 7). No patients had
      neurological worsening. Eight of 13 patients with incomplete deficits had some
      improvement in American Spinal Injury Association score. CONCLUSIONS: This is the
      first prospective application of the SLIC system. With regard to our primary
      outcome, neurological status, the SLIC system was found to be a safe and
      effective guide in the surgical treatment of SCST.

PMID- 24090540
TI  - Retinal pigment epithelium (RPE) cytoskeleton in vivo and in vitro.
AB  - The retinal pigment epithelium (RPE) constitutes a monolayer of cuboidal cells
      that interact apically with the interphotoreceptor matrix (IPM) and outer
      segments of the photoreceptor cells and basally with the subjacent Bruch's
      membrane. This highly polarized structure is maintained by the cytoskeleton of
      individual cells and their interactions at the basolateral junctional complexes
      that stabilize this epithelial structure. This RPE complex network of filaments,
      tubules and associated proteins is modeled by the cellular environment, the RPE
      intercellular interactions, and by its interactions with the extracellular
      matrix. This is a review of the key features of the RPE cytoskeleton in vivo and
      in vitro. 

PMID- 24090541
TI  - Tenacibaculum maritimum infection: pathology and immunohistochemistry in
      experimentally challenged turbot (Psetta maxima L.).
AB  - Tenacibaculum maritimum is the causative agent of tenacibaculosis, a bacterial
      disease with a worldwide distribution, which causes important losses in the
      turbot aquaculture. Despite the importance of this bacterium, little is known
      about pathogenesis of the tenacibaculosis, pattern of lesions and the portal of
      entry of T. maritimum. Turbots (Psetta maxima) were experimentally infected with
      T. maritimum using subcutaneous and intraperitoneal routes of inoculation and
      samples of skin and internal organs were taken throughout the assay. Fish
      inoculated by both infection routes suffered a septicaemia but only the
      subcutaneous inoculation reproduces the disease signs described in natural
      outbreaks. Bacterial antigen was detected by immunohistochemistry in the internal
      organs 3 h after infection in fish inoculated by subcutaneous route and 6 h after
      the inoculation of fish by intraperitoneal route. In summary, both routes of
      inoculation are able to cause an infection and bacteraemia in the fish. However,
      subcutaneous inoculation route reproduces the disease in a faster and more
      reliable way than the intraperitoneal route. Moreover, bacterium spreads along
      the internal organs easily, but needs a gateway to penetrate in the organism and
      this portal of entry could be skin. 

PMID- 24090543
TI  - Absence of an ideal single-walled carbon nanotube forest structure for thermal
      and electrical conductivities.
AB  - We report the fundamental dependence of thermal diffusivity and electrical
      conductance on the diameter and defect level for vertically aligned single-walled
      carbon nanotube (SWCNT) forests. By synthesizing a series of SWCNT forests with
      continuous control of the diameter and defect level over a wide range while
      holding all other structures fixed, we found an inverse and mutually exclusive
      relationship between the thermal diffusivity and the electrical conductance. This
      relationship was explained by the differences in the fundamental mechanisms
      governing each property and the optimum required structures. We concluded that
      high thermal diffusivity and electrical conductance would be extremely difficult
      to simultaneously achieve by a single SWCNT forest structure within current
      chemical vapor deposition synthetic technology, and the "ideal" SWCNT forest
      structure would differ depending on application. 

PMID- 24090542
TI  - Perceptions of child discipline and its contributions to child abuse in a low
      income community in Nairobi, Kenya.
AB  - BACKGROUND: There is a fine line between child discipline and maltreatment.
      Perceptions of child discipline in three tribal groups living in an informal
      community in Kenya are reported. METHODS: Child disciplinary practices in the
      Kibera community of Nairobi were surveyed among three tribal groups (the Luo,
      Luyha and Nubi) to determine perceptions and modes of discipline and what was
      perceived as excessive. RESULTS: A random sample of 538 adults with children <18
      years; 73% were mothers and 20% fathers. Overall, 98% had ever disciplined a
      child; 376 (70%) understood discipline to mean showing love and praising children
      when they do good but punishing wrong-doing, and 108 (20%) understood it to mean
      beating children whenever they do wrong. The majority said children should be
      disciplined by the mother (62%), father (47%) or whoever is around at the time of
      the offence (57%). It was deemed acceptable that teachers discipline children by
      11% of the Luos, 23% of the Luhya and 34% of the Nubi. The most commonly used
      method was caning, used by 520 (97%), then pinching (40%), slapping (33%),
      pulling ears (20%) and denying food (19%). Sixty-three per cent of parents
      recognized that excessive punishment could cause fainting, and 64% that it could
      cause death. Factors reported as contributing to excessive discipline were
      domestic tension, poverty, stress and 'difficult children'. CONCLUSION: There
      were consistent patterns of child discipline in three tribal groups living in
      Nairobi. There was a high prevalence of excessive discipline in the form of
      physical abuse, and clinicians should be aware of the signs of excessive
      discipline and be prepared to act in the interests of the child's welfare.

PMID- 24090545
TI  - Characterization of the pelagic fish community of the north-western and northern
      Spanish shelf waters.
AB  - This study demonstrates the utility of trawl data, collected during acoustic
      surveys of pelagic fish stocks as a way of confirming fish identification, to
      characterize the pelagic community, as well as allowing description and
      prediction of fish distribution patterns, based on data from Spanish Atlantic
      Ocean shelf surveys during spring 2005-2011. The composition of the pelagic
      community is described, as well as spatial and temporal patterns of variation in
      both the community composition and the presence and importance of two of the main
      exploited pelagic species, sardine Sardina pilchardus and anchovy Engraulis
      encrasicolus. The most important species in terms of both frequency of occurrence
      and standardized mass in hauls were mackerel Scomber scombrus, hake Merluccius
      merluccius, horse mackerel Trachurus trachurus, S. pilchardus and bogue Boops
      boops. Multivariate analysis indicated significant effects of depth, geographical
      area and year on haul composition. Descriptive generalized additive models (GAM),
      with latitude, longitude and depth as predictors, identified clear spatial
      patterns in the occurrence and abundance of both S. pilchardus and E.
      encrasicolus, with abundance being highest closer to the coast and, in the case
      of E. encrasicolus, higher near the French and Portuguese borders. Further GAM
      analysis, using environmental variables to explain spatial patterns, revealed
      significant effects of depth and sea surface temperature (SST) gradient and depth
      on S. pilchardus importance, while E. encrasicolus importance was related to SST.
      The importance of both species in hauls was higher in the years of higher
      spawning stock biomass (SSB) and E. encrasicolus also appeared to expand its
      range when SSB was higher. 

PMID- 24090546
TI  - A visual survey technique for deep-water fishes: estimating anglerfish Lophius
      spp. abundance in closed areas.
AB  - A visual survey technique was employed to estimate the abundance and distribution
      of anglerfish Lophius spp. in areas where destructive sampling methods, such as
      trawling, are unacceptable. To enable visual surveying at depths of over 300 m, a
      deep towed vehicle was developed equipped with video, lights and other sensors
      and was towed at speeds of up to 1.5 m s-1 and altitudes of up to 10 m (from the
      seabed) to survey large areas of the seabed around the Rockall Bank in the north
      west Atlantic Ocean. The system allowed for areas up to 125 000 m2 to be
      surveyed, a substantial area comparable to that surveyed by demersal-trawl
      sampling. Lophius spp. densities ranged from 15 to 736 fish km-2; these are
      comparable to estimated Lophius spp. densities determined by trawl surveys in
      adjacent areas. Estimates of Lophius spp. abundance in the closed areas ranged
      between 99,855 and 176,887 for the time series considered (2007-2011).

PMID- 24090547
TI  - Anguillids: conserving a global fishery.
AB  - Concern has increased in recent years over the sustainability of anguillid
      populations worldwide in the face of sustained consumer demand. This is as true
      of the more numerous tropical species as it is for the better known temperate
      species. There are, however, critical gaps in knowledge of anguillid biology and
      ecology, and these hold back measures designed to conserve and enhance anguillid
      populations, including aquaculture. Developing a more integrated understanding of
      anguillid biology, and resolving challenges faced by stakeholders and policy
      makers, is now more urgent than ever. World experts from Japan, the U.S.A.,
      Canada, the European Union and New Zealand led a 3 day event where >200
      scientists drawn from >30 countries across the globe converged to share their
      experience and expert knowledge of anguillids. The session covered the full range
      of issues affecting anguillid stocks across the globe, and also highlighted
      advances in the understanding of fundamental aspects of anguillid biology.
      Overall, 49 oral presentations and 68 posters were presented and, while these
      were dominated by Anguilla anguilla, Anguilla rostrata and Anguilla japonica, a
      further eight anguillid species were represented. What was experienced by all was
      the facilitation of a more integrated understanding of anguillid biology, and how
      this understanding can interface with the challenges faced by fishermen,
      consumers, engineers, producers and managers. The highlights are reviewed,
      important trends in anguillid stocks and research identified and the consensus
      for future science and management direction reported. 

PMID- 24090548
TI  - Causes and methods to estimate cryptic sources of fishing mortality.
AB  - Cryptic, not readily detectable, components of fishing mortality are not
      routinely accounted for in fisheries management because of a lack of adequate
      data, and for some components, a lack of accurate estimation methods. Cryptic
      fishing mortalities can cause adverse ecological effects, are a source of
      wastage, reduce the sustainability of fishery resources and, when unaccounted
      for, can cause errors in stock assessments and population models. Sources of
      cryptic fishing mortality are (1) pre-catch losses, where catch dies from the
      fishing operation but is not brought onboard when the gear is retrieved, (2)
      ghost-fishing mortality by fishing gear that was abandoned, lost or discarded,
      (3) post-release mortality of catch that is retrieved and then released alive but
      later dies as a result of stress and injury sustained from the fishing
      interaction, (4) collateral mortalities indirectly caused by various ecological
      effects of fishing and (5) losses due to synergistic effects of multiple
      interacting sources of stress and injury from fishing operations, or from
      cumulative stress and injury caused by repeated sub-lethal interactions with
      fishing operations. To fill a gap in international guidance on best practices,
      causes and methods for estimating each component of cryptic fishing mortality are
      described, and considerations for their effective application are identified.
      Research priorities to fill gaps in understanding the causes and estimating
      cryptic mortality are highlighted. 

PMID- 24090549
TI  - Composition and diversity patterns of megafauna discards in the deep-water shrimp
      trawl fishery off Brazil.
AB  - Composition and spatial diversity patterns of retained and discarded catches in
      the deep-water shrimp (family Aristeidae) trawling fishery off Brazil were
      assessed by observers on-board commercial operations in 2005 and 2006. These
      trawls caught 19,440 kg and 180,076 individuals of which 76.0 and 65.2%,
      respectively, were discarded at sea. Finfishes represented 54% of the numerical
      catch but were almost fully discarded (98%). Crustaceans represented 40% of the
      numerical catch and were mostly retained (80%). The scarlet shrimp Aristaeopsis
      edwardsiana comprised approximately half of the retained catch. The remainder of
      the retained proportion comprised mainly the red giant shrimp Aristaeomorpha
      foliacea, the alistado shrimp Aristeus antillensis and small quantities of
      Argentine hake Merluccius hubbsi and gulf hake Urophycis mystacea. Discards
      comprised 108 species including 72 fish species, 19 crustaceans and 10
      cephalopods. The large-scaled lanternfish Neoscopelus macrolepidotus was dominant
      in the discards, followed by the benthopelagic fishes Monomitopus agassizii,
      Synagrops bellus, Dibranchus atlanticus and Gadella imberbis and various macrurid
      species. This fishery was restricted to a limited bathymetric range (700-800 m),
      where discrete megafauna assemblages exist and may have been significantly
      affected.

PMID- 24090550
TI  - Assessing the sensitivity of habitats to fishing: from seabed maps to sensitivity
      maps.
AB  - In the Welsh part of the Irish Sea, a method was developed for assessing the
      sensitivity of different seabed habitats to existing fishing activities, across a
      range of potential fishing intensities. The resistance of 31 habitats and their
      associated biological assemblage to damage by 14 categories of fishing activity
      were assessed along with the rate at which each habitat would recover following
      impact (resilience). Sensitivity was scored based on a combination of the
      resistance of a habitat to damage and its subsequent rate of recovery. The
      assessments were based, wherever possible, on scientific literature, with expert
      judgement used to extrapolate results to habitat and gear combinations not
      directly examined in the published literature. The resulting sensitivity matrices
      were then subject to further peer review at a series of workshops. Following
      consensus on the habitat sensitivity, these data were combined with the most
      resolved sea-floor habitat maps. These habitat sensitivity maps can help inform
      the development of site-specific management plans, as well as having a place in
      spatial planning and aiding managers in developing dialogue with other
      stakeholders. A case study of their application is provided. 

PMID- 24090551
TI  - Vulnerability of artisanal fisheries to climate change in the Venice Lagoon.
AB  - Within the context of global warming, the western coast of the northern Adriatic
      Sea can be regarded as an extremely vulnerable area. Owing to the local
      geographic features, this area has been described as the Venetian lacuna, where
      Mediterranean Sea climatic conditions are replaced by Atlantic Ocean ones,
      supporting the presence of glacial relicts, such as sprat Sprattus sprattus,
      flounder Platichthys flesus and brown shrimp Crangon crangon. Nektonic assemblage
      therefore represents a good candidate in terms of an early proxy for thermal
      regime alterations. It represents a dynamic component of the lagoon ecosystem,
      changing in space and time, actively moving through the entire system, and
      dynamically exchanging with the open sea. Here, the first signals of the change
      have been already detected, such as the presence of alien thermophilic species.
      Within this context, since the beginning of the century, sampling of the nektonic
      assemblage has been carried out, integrating them with landings data from the
      fish market. Vulnerabilities to thermal regime changes have been tested by (1)
      categorizing species according to the mean distribution area in terms of
      latitudinal range (over 45 degrees , 30 degrees -45 degrees  and below 30 degrees
      ), and (2) analysing both spatial and temporal variations within fishing grounds.
      Results indicated a high potential vulnerability of the artisanal fishery to
      climate change, as the commercial catch is entirely composed of species from cold
      (>45 degrees  N) and temperate (between 45 degrees  and 30 degrees  N) latitudes.
      At present no alien thermophilic species have been recorded within the lagoon,
      which is possibly a sign of good resilience of the assemblage. Finally, abundance
      of species from cold latitudes has decreased during the past decade. All of this
      has been discussed in the context of the mean annual temperature trend. 

PMID- 24090552
TI  - Improvements to Rapfish: a rapid evaluation technique for fisheries integrating
      ecological and human dimensions.
AB  - This paper reports recent developments in Rapfish, a normative, scalable and
      flexible rapid appraisal technique that integrates both ecological and human
      dimensions to evaluate the status of fisheries in reference to a norm or goal.
      Appraisal status targets may be sustainability, compliance with a standard (such
      as the UN code of conduct for responsible fisheries) or the degree of progress in
      meeting some other goal or target. The method combines semi-quantitative (e.g.
      ecological) and qualitative (e.g. social) data via multiple evaluation fields,
      each of which is assessed through scores assigned to six to 12 attributes or
      indicators: the scoring method allows user flexibility to adopt a wide range of
      utility relationships. For assessing sustainability, six evaluation fields have
      been developed: ecological, technological, economic, social, ethical and
      institutional. Each field can be assessed directly with a set of scored
      attributes, or several of the fields can be dealt with in greater detail using
      nested subfields that themselves comprise multidimensional Rapfish assessments
      (e.g. the hierarchical institutional field encompasses both governance and
      management, including a detailed analysis of legality). The user has the choice
      of including all or only some of the available sustainability fields. For the
      attributes themselves, there will rarely be quantitative data, but scoring allows
      these items to be estimated. Indeed, within a normative framework, one important
      advantage with Rapfish is transparency of the rigour, quality and replicability
      of the scores. The Rapfish technique employs a constrained multidimensional
      ordination that is scaled to situate data points within evaluation space. Within
      each evaluation field, results may be presented as a two-dimensional plot or in a
      one-dimensional rank order. Uncertainty is expressed through the probability
      distribution of Monte-Carlo simulations that use the C.L. on each original
      observation. Overall results of the multidisciplinary analysis may be shown using
      kite diagrams that compare different locations, time periods (including future
      projections) and management scenarios, which make policy trade-offs explicit.
      These enhancements are now available in the R programming language and on an open
      website, where users can run Rapfish analyses by downloading the software or
      uploading their data to a user interface.

PMID- 24090553
TI  - Emerging asymmetric interactions between forage and predator fisheries impose
      management trade-offs.
AB  - A size and trait-based marine community model was used to investigate
      interactions, with potential implications for yields, when a fishery targeting
      forage fish species (whose main adult diet is zooplankton) co-occurs with a
      fishery targeting larger-sized predator species. Predicted effects on the size
      structure of the fish community, growth and recruitment of fishes, and yield from
      the fisheries were used to identify management trade-offs among the different
      fisheries. Results showed that moderate fishing on forage fishes imposed only
      small effects on predator fisheries, whereas predator fisheries could enhance
      yield from forage fisheries under some circumstances. 

PMID- 24090554
TI  - Close cooperation between science, management and industry benefits sustainable
      exploitation of the Falkland Islands squid fisheries.
AB  - The Falkland Islands fishing industry is unique, as 60-80% of its annual catch
      consists of two squid species, Illex argentinus and Doryteuthis gahi. Short
      annual life cycles make both species susceptible to intra-annual environmental
      changes, resulting in large biomass fluctuations that must be addressed in
      management of the stocks. In the D. gahi fishery, short chains of communication
      between science, management and industry allow effective cooperation in the
      interest of long-term sustainable exploitation. The industry is responsive to
      short-notice requests for in-season information about the fishery. Management
      takes into account both scientific advice and industry recommendations, through
      ongoing consultations before and during the fishing seasons. As a result of this
      cooperation, D. gahi is one of the best managed squid fisheries in the world with
      local fishing companies being amongst the largest and most profitable enterprises
      in the Falklands economy. The I. argentinus fishery has the same potential, but a
      further level of cooperative management is needed as this squid is a straddling
      stock between several countries and the high seas. Development of a regional
      fisheries management organization in the South Atlantic Ocean is required to
      control multilateral exploitation and ensure long-term sustainability of I.
      argentinus stocks. 

PMID- 24090555
TI  - A medium-term, stochastic forecast model to support sustainable, mixed fisheries
      management in the Mediterranean Sea.
AB  - A medium-term (10 year) stochastic forecast model is developed and presented for
      mixed fisheries that can provide estimations of age-specific parameters for a
      maximum of 10 stocks and 10 fisheries. Designed to support fishery managers
      dealing with complex, multi-annual management plans, the model can be used to
      quantitatively test the consequences of various stock-specific and fishery
      specific decisions, using non-equilibrium stock dynamics. Such decisions include
      fishing restrictions and other strategies aimed at achieving sustainable mixed
      fisheries consistent with the concept of maximum sustainable yield (MSY). In
      order to test the model, recently gathered data on seven stocks and four
      fisheries operating in the Ligurian and North Tyrrhenian Seas are used to
      generate quantitative, 10 year predictions of biomass and catch trends under four
      different management scenarios. The results show that using the fishing mortality
      at MSY as the biological reference point for the management of all stocks would
      be a strong incentive to reduce the technical interactions among concurrent
      fishing strategies. This would optimize the stock-specific exploitation and be
      consistent with sustainability criteria. 

PMID- 24090556
TI  - Effects of a large northern European no-take zone on flatfish populations.
AB  - In March 2006, a 360 km2 no-take zone (NTZ) was established north of Gotland in
      the central Baltic Sea, with the purpose to scientifically evaluate the effects
      of a fishing ban on flatfish populations. A monitoring programme was set up to
      study the populations in the NTZ and in a reference area east of Gotland where
      the fishing pressure was high. The programme included fishing with multimesh
      survey nets, modelling of potential larval export and estimation of fish
      consumption by large marine predators. Overall, the results showed a clear
      positive effect of the NTZ on turbot Scophthalmus maximus, with higher densities
      in the closed area compared with the fished area and also higher densities after
      closure compared with before. The NTZ also had older individuals and a more even
      sex ratio. This, in combination with a high potential for larval export from the
      NTZ to Gotland, shows that the marine reserve may be important for maintaining a
      viable S. maximus stock at Gotland. Also, for flounder Platichthys flesus, the
      densities were higher in the NTZ compared to the reference area and there was a
      net larval export to the fished area. For both species, density-dependent growth
      was evident, with a lower length at age in the closed area. Potential predation
      by grey seal Halichoerus grypus and great cormorant Phalacrocorax carbo sinesis
      on flatfishes, that could hamper the evaluation of the marine reserve, was also
      addressed. Taken together, the results show that there are clear benefits of the
      fishing ban for both flatfish species within the NTZ, while the net effects on
      fisheries are difficult to quantify.

PMID- 24090557
TI  - The optimal process of self-sampling in fisheries: lessons learned in the
      Netherlands.
AB  - At-sea sampling of commercial fishery catches by observers is a relatively
      expensive exercise. The fact that an observer has to stay on-board for the
      duration of the trip results in clustered samples and effectively small sample
      sizes, whereas the aim is to make inferences regarding several trips from an
      entire fleet. From this perspective, sampling by fishermen themselves (self
      sampling) is an attractive alternative, because a larger number of trips can be
      sampled at lower cost. Self-sampling should not be used too casually, however, as
      there are often issues of data-acceptance related to it. This article shows that
      these issues are not easily dealt with in a statistical manner. Improvements
      might be made if self-sampling is understood as a form of cooperative research.
      Cooperative research has a number of dilemmas and benefits associated with it.
      This article suggests that if the guidelines for cooperative research are taken
      into account, the benefits are more likely to materialize. Secondly,
      acknowledging the dilemmas, and consciously dealing with them might lay the basis
      to trust-building, which is an essential element in the acceptance of data
      derived from self-sampling programmes. 

PMID- 24090558
TI  - Involving stakeholders in the commissioning and implementation of fishery science
      projects: experiences from the U.K. Fisheries Science Partnership.
AB  - Following from similar initiatives worldwide, the U.K.'s Fisheries Science
      Partnership (FSP) was established in 2003 to provide the fishing industry with
      opportunities to propose and participate in scientific studies in collaboration
      with fishery scientists. Key concepts were that most of the available funding
      would support industry participation, that industry, not scientists, would come
      up with the ideas for projects, and that commercial fishing vessels and fishing
      methods would be used to address specific concerns of the fishing industry in a
      scientifically controlled manner. Nearly 100 projects had been commissioned by
      March 2012, covering annual time-series surveys of stocks subject to traditional
      assessment, and ad hoc projects on, e.g. gear selectivity, discard survival,
      tagging and migration and fishery development. The extent to which the results of
      the projects have been used by stakeholders, fishery scientists and fishery
      managers at a national and E.U. level is evaluated, along with the degree of
      industry interest and involvement, and reasons are identified for successes or
      failures in the uptake of the results into management and policy. Finally, the
      question is posed whether the programme has been successful in improving the
      engagement of the fishing community in the science-management process and in
      fostering communication and greater trust between fishers, scientists and
      managers. 

PMID- 24090559
TI  - Failure to engage the public in issues related to inland fishes and fisheries:
      strategies for building public and political will to promote meaningful
      conservation.
AB  - Generating awareness of environmental conservation issues among the public is
      essential if there is an expectation of them to alter their behaviour, facilitate
      informed decisions and engage governments or regulatory authorities to take
      action. There are, however, exceedingly few public engagement success stories
      related to inland fishes and fisheries policy and resource allocation decisions.
      Inland aquatic resources and their associated fisheries provide employment,
      recreation, culture and, in developing regions, a considerable proportion of
      human nutrition and food security. Freshwater fishes are incredibly diverse but
      are among the most endangered organisms globally. Many threats to inland
      fisheries are driven largely by externalities to inland fisheries. The purpose of
      this paper is to draw attention to the role and plight of inland fishes and
      fisheries, and the need to generate the public and political will necessary to
      promote meaningful conservation. With this paper, the extent to which the
      scientific and environmental management communities have failed to engage the
      public in issues related to inland fishes and fisheries is characterized. Next,
      the barriers or factors that serve as the basis for the problem with public
      engagement are identified. The paper concludes by identifying strategies,
      including those focused on environmental education initiatives, for building the
      public and political will necessary to promote meaningful conservation of inland
      fishes and fisheries in developed and developing countries. Scientists,
      environmental managers, non-governmental organizations, politicians, regulatory
      authorities and the media all have important roles to play in overcoming
      challenges to inland fisheries. Failure to engage the public in freshwater
      conservation and management issues will impede efforts to stem the loss of
      freshwater habitats, fisheries and aquatic biodiversity. Thankfully, there are
      opportunities to learn from success stories related to other environmental issues
      and initiatives that have been successful in marine fish conservation. 

PMID- 24090560
TI  - Cooperation between scientists, NGOs and industry in support of sustainable
      fisheries: the South African hake Merluccius spp. trawl fishery experience.
AB  - This paper examines the increasingly close interaction between natural and social
      scientists, non-governmental organizations (NGO) and industry, in pursuit of
      responsible ecosystem-based management of fisheries. South Africa has committed
      to implementing an ecosystem approach to fisheries management. Management advice
      stems from multi-stakeholder representation on government-led scientific and
      management working groups. In the hake Merluccius capensis and Merluccius
      paradoxus fishery, the primary management measure is an annual total allowable
      catch (TAC), the level of which is calculated using a management procedure (MP)
      that is revised approximately every 4 years. Revision of the MP is a consultative
      process involving most stakeholders, and is based on simulation modelling of
      projected probable scenarios of resource and fishery dynamics under various
      management options. NGOs, such as the Worldwide Fund for Nature in South Africa
      (WWF-SA), have played an important role in influencing consumers, the fishing
      industry and government to develop responsible fishing practices that minimize
      damage to marine ecosystems. Cooperation between industry, government and
      scientists has helped to improve sustainability and facilitated the meeting of
      market-based incentives for more responsible fisheries. Research includes
      ecosystem modelling, spatial analysis and ecosystem risk assessment with
      increasing research focus on social and economic aspects of the fishery. A four
      year cooperative experiment to quantify the effect of trawling on benthic
      community structure is being planned. The food requirements of top predators
      still need to be included in the TAC-setting formulae and more social and
      economic research is needed. This paper also demonstrates how NGO initiatives
      such as Marine Stewardship Council certification and the Southern African
      Sustainable Seafood Initiative, a traffic light system of classifying seafood for
      consumers, have contributed to responsible fishing practices, increased ecosystem
      research and public awareness. This fishery appears to have a good future,
      provided that the monitoring, control and surveillance systems continue to
      function, TACs remain within ecologically sustainable limits and the effective
      collaboration between government, industry, scientists and NGOs continues to
      drive positive change. 

PMID- 24090561
TI  - Determining the effect of environmental accidents on responses to a Gulf of
      Mexico recreational for-hire fishing industry survey.
AB  - A survey designed to collect economic, attitudinal and policy data from the
      recreational for-hire (RFH) fishing industry in the U.S. Gulf of Mexico was
      conducted before and during the largest marine oil spill in U.S. history (the
      April 2010 Deepwater Horizon blowout). Respondents were grouped into two time
      periods based on when the survey was completed, where the break in groups was
      determined through the examination of the Pew Research Center's media coverage
      index and the per cent of fishing area closures due to the oil spill. A logistic
      regression was used to test variables that might predict the time period of a
      response. Results indicated that recall bias was not present in the financial
      variables examined, but that firm operating and demographic characteristics (i.e.
      vessel size, annual number of trips, number of vessels operating in the firm,
      tenure and household income) were significant in explaining the time period in
      which surveys were completed. 

PMID- 24090562
TI  - Global fishmeal and fish-oil supply: inputs, outputs and markets.
AB  - Recent data on fishmeal and fish-oil supply are presented identifying key
      producer countries and raw material sources and distinguishing between whole fish
      and by-products. The conversion of these raw materials into marine ingredients is
      discussed and global volumes presented. This is followed by a summary of the main
      countries using these marine ingredients over recent years. Uses of fishmeal and
      fish-oil by market segment are then presented. From this, a global mass balance
      of inputs and outputs is derived which allows the calculation of the input-to
      output ratios (fish in:fish out; FIFO) for the main aquaculture production types
      to be made. Current areas of focus by the industry include the need to
      demonstrate sustainable practice, more strategic use of marine ingredients,
      greater use of fishery and land-animal by-products as well as vegetable
      substitutes, and novel sources of essential omega-3 fats, notably the long-chain
      polyunsaturated fatty acids, eicosapentaenoic (EPA) and docosahexaenoic (DHA)
      acids. Implications are drawn for future supply prospects of fishmeal and fish
      oil and their future role in aquaculture, agriculture and human health. 

PMID- 24090563
TI  - Meeting the food and nutrition needs of the poor: the role of fish and the
      opportunities and challenges emerging from the rise of aquaculture.
AB  - People who are food and nutrition insecure largely reside in Asia and Sub-Saharan
      Africa and for many, fish represents a rich source of protein, micronutrients and
      essential fatty acids. The contribution of fish to household food and nutrition
      security depends upon availability, access and cultural and personal preferences.
      Access is largely determined by location, seasonality and price but at the
      individual level it also depends upon a person's physiological and health status
      and how fish is prepared, cooked and shared among household members. The
      sustained and rapid expansion of aquaculture over the past 30 years has resulted
      in >40% of all fish now consumed being derived from farming. While aquaculture
      produce increasingly features in the diets of many Asians, it is much less
      apparent among those living in Sub-Saharan Africa. Here, per capita fish
      consumption has grown little and despite the apparently strong markets and
      adequate biophysical conditions, aquaculture has yet to develop. The contribution
      of aquaculture to food and nutrition security is not only just an issue of where
      aquaculture occurs but also of what is being produced and how and whether the
      produce is as accessible as that from capture fisheries. The range of fish
      species produced by an increasingly globalized aquaculture industry differs from
      that derived from capture fisheries. Farmed fishes are also different in terms of
      their nutrient content, a result of the species being grown and of rearing
      methods. Farmed fish price affects access by poor consumers while the size at
      which fish is harvested influences both access and use. This paper explores these
      issues with particular reference to Asia and Africa and the technical and policy
      innovations needed to ensure that fish farming is able to fulfil its potential to
      meet the global population's food and nutrition needs. 

PMID- 24090564
TI  - Bevacizumab in HIV-positive patients: concerns about safety and potential for
      therapeutic use.
AB  - Human immunodeficiency virus (HIV) patients have more aggressive presentation of
      colorectal cancer (CRC) and less favourable outcome. Bevacizumab is an
      antiangiogenic agent that has emerged as a major drug for metastatic CRC.
      However, few data are available on the safety of bevacizumab in HIV patients. In
      the light of a case study, we briefly draw intention on how angiogenesis
      inhibitors could interact with antiviral tri-therapy. 

PMID- 24090565
TI  - Specific antibody to a conserved region of Babesia apical membrane antigen-1
      inhibited the invasion of B. bovis into the erythrocyte.
AB  - Apical membrane antigen-1 (AMA-1) is a microneme protein that exists in all
      apicomplexan parasites and plays an indispensable role in the invasion into host
      cell. Central region of ectodomains I and II of Babesia bovis apical membrane
      antigen-1 (BbAMA-1P) is highly conserved with these of Babesia species and may be
      beneficial for vaccine development against babesiosis. In the present study,
      recombinant protein encoding the central region of B. bovis AMA-1 (rBbAMA-1P) was
      produced in Escherichia coli and its antiserum was prepared in mice for further
      molecular characterization. Anti-rBbAMA-1P serum specifically reacted with
      corresponding authentic protein of B. bovis as determined by Western blotting and
      IFAT. Cultured B. bovis treated with anti-rBbAMA-1P serum showed significant
      reduction in the in vitro growth of the parasites. Moreover, preincubated free
      merozoites with 1mg/ml anti-rBbAMA-1P serum inhibited their efficiency in the
      invasion into erythrocytes (RBCs) by 61% and 70% at 3h and 6h, respectively. Our
      data suggest that the central region of domains I and II of BbAMA-1 may serve as
      a vaccine candidate against babesiosis. 

PMID- 24090566
TI  - De novo whole transcriptome analysis of the fish louse, Argulus siamensis: first
      molecular insights into characterization of Toll downstream signalling molecules
      of crustaceans.
AB  - Argulus siamensis is a major ectoparasitic pathogen of freshwater fish capable of
      causing substantial economic loss. None of the available control measures have
      been able to address the problem of argulosis resourcefully. To combat this
      pathogen effectively, it is necessary to have a comprehensive understanding of
      its life processes with information on various genes involved. The transcriptome
      studies can generate introductory information about genes participating in
      physiological processes of the parasite which could be targeted for their
      control. In this study, the transcriptome sequencing of A. siamensis was
      performed on Illumina HiSeq 2000 platform which generated 75,126,957 high quality
      reads. A total of 46,352 transcript contigs were assembled with average length of
      1211bp and N50 length of 2302bp. In total, 19,290 CDS including 184 novel CDS and
      59,019 open reading frames (ORFs) were identified from the assembled contigs.
      Gene ontology and Kyoto Encylopedia of Genes and Genomes pathway analysis were
      performed to classify contigs into their functional categories and regulation
      pathways. Additionally, 1171 simple sequence repeats were identified from the
      assembled contigs. Further, twelve contigs with high similarity with downstream
      molecules of the mammalian toll like receptor (TLR) pathway were validated by
      their inductive expressions in response to lipopolysaccharide (LPS) of Gram
      negative bacteria, Escherichia coli and Gram positive bacteria, Staphylococcus
      aureus. The transcriptome of an ectoparasite A. siamensis was sequenced,
      assembled, annotated, and the downstream signalling molecules of Toll pathway
      characterized. The transcriptome data generated will facilitate studies on
      functional genomics that will subsequently be applied for vaccine development and
      other control strategies against the parasite. 

PMID- 24090567
TI  - Increased action of triclabendazole (TCBZ) in vitro against a TCBZ-resistant
      isolate of Fasciola hepatica following its co-incubation with the P-glycoprotein
      inhibitor, R(+)-verapamil.
AB  - A study has been carried out to investigate whether the action of triclabendazole
      (TCBZ) against Fasciola hepatica is altered by inhibition of P-glycoprotein (Pgp)
      linked drug efflux pumps. The Sligo TCBZ-resistant fluke isolate was used for
      these experiments and the Pgp inhibitor selected was R(+)-verapamil [R(+)-VPL].
      In the first experiment, flukes were initially incubated for 2h in R(+)-VPL
      (1*10(-4) M), then incubated in R(+)-VPL + triclabendazole sulphoxide (TCBZ.SO)
      (50MUg/ml) until flukes ceased movement (at 9h post-treatment). In a second
      experiment, flukes were incubated in TCBZ.SO alone and removed from the
      incubation medium following cessation of motility (after 15h). In the third
      experiment, flukes were incubated for 24h in R(+)-VPL on its own. Changes to the
      tegumental system and gut following drug treatment and following Pgp inhibition
      were assessed by means of light microscope histology and transmission electron
      microscopy. Incubation of the Sligo isolate in either R(+)-VPL or TCBZ.SO on
      their own had a limited impact on the tegumental syncytium and tegumental cells;
      the changes were consistent with a stress response by the fluke to drug action.
      Greater disruption was observed when the drugs were combined, in terms of the
      vacuolation and sloughing of the syncytium, spine disruption and the cessation of
      secretory activity in, and degradation of, the tegumental cells. In the gut,
      treatment with R(+)-VPL on its own did not lead to any cellular changes. Some
      limited changes to the mitochondria and the granular endoplasmic reticulum were
      observed after incubation in TCBZ.SO alone, together with reduced secretory
      activity and evidence of autophagy. However, these changes were far more
      pronounced in combination-treated flukes. The results of this study support the
      concept of altered drug efflux in TCBZ-resistant flukes and indicate that drug
      transporters may play a role in the development of drug resistance. 

PMID- 24090568
TI  - Identification of novel B cell epitopes within Toxoplasma gondii GRA1.
AB  - Newly synthesized epitopes are one of the most promising antigens for the
      development of diagnostic kits and peptide vaccines. Very little is known about
      the B cell epitopes on GRA1 of Toxoplasma gondii, which are recognized by the
      humoral immune response in pigs. In this study, epitopes derived from GRA1 of T.
      gondii were identified using synthetic peptide techniques and bioinformatics.
      Three (PG10, PG13 and PG18) out of the eighteen peptides tested were recognized
      by all pig sera from different time points after infection, and the other
      peptides were recognized by select sera from various time points after infection.
      Our data indicate that many regions of GRA1, and in particular, the regions
      represented by the peptides PG10, PG13 and PG18, are involved in the pig antibody
      response. The identification of specific epitopes targeted by the host antibody
      response is important both for understanding the natural response to infection
      and for the development of epitope-based marker vaccines and diagnostic tools for
      toxoplasmosis. 

PMID- 24090569
TI  - Antiparasitic effect of a fraction enriched in tight-binding protease inhibitors
      isolated from the Caribbean coral Plexaura homomalla.
AB  - Malaria and American Trypanosomiasis constitute major global health problems. The
      continued emergence and spreading of resistant strains and the limited efficacy
      and/or safety of currently available therapeutic agents require a constant search
      for new sources of antiparasitic compounds. In the present study, a fraction
      enriched in tight-binding protease inhibitors was isolated from the Caribbean
      coral Plexaura homomalla (Esper, 1792), functionally characterized and tested for
      their antiparasitic activity against Trypanosoma cruzi and Plasmodium falciparum.
      The resultant fraction was chromatographically enriched in tight-binding
      inhibitors active against Papain-like cysteine peptidases (92%) and Pepsin-like
      aspartyl peptidases (8%). Globally, the inhibitors present in the enriched
      fraction showed no competition with substrates and apparent Ki values of 1.99 and
      4.81nM for Falcipain 2 and Cruzipain, the major cysteine peptidases from P.
      falciparum and T. cruzi, respectively. The inhibitor-enriched fraction showed
      promising antiparasitic activity in cultures. It reduced the growth of the
      chloroquine-resistant P. falciparum strain Dd2 (IC50=0.46MUM) and promoted the
      apparent accumulation of trophozoites, both consistent with a blockade in the
      hemoglobin degradation pathway. At sub-micromolar concentrations, the inhibitor
      enriched fraction reduced the infection of VERO cells by T. cruzi (CL Brener
      clone) trypomastigotes and interfered with intracellular differentiation and/or
      replication of the parasites. This study provides new scientific evidence that
      confirms P. homomalla as an excellent source of tight-biding protease inhibitors
      for different proteases with biomedical relevance, and suggests that either the
      individual inhibitors or the enriched fraction itself could be valuable as
      antiparasitic compounds. 

PMID- 24090570
TI  - Arginase activity is associated with fibrosis in experimental infection with
      Taenia crassiceps, but does not play a major role in resistance to infection.
AB  - Murine infection with Taenia crassiceps cysticerci is used as an experimental
      model for human and animal cysticercosis. In this infection parasites can be
      found associated with an inflammatory infiltrate enriched with macrophages.
      Experimental evidence exists supporting a role for either NO-producing
      classically activated (CAMPhi) or arginase- and CD301-expressing alternatively
      activated macrophages (AAMPhi) in T. crassiceps resistance. In both cell types,
      arginine is utilized as an important mediator in macrophage effector functions.
      To investigate whether there is an association between arginine availability,
      susceptibility to T. crassiceps and other parameters such as fibrosis, BALB/c
      mice were infected intraperitoneally with cysticerci and treated daily with the
      arginase inhibitor nor-NOHA or supplemented with l-arginine and followed for
      eight weeks. The numbers and developmental stages of parasites were evaluated as
      well as the presence of CD301+ AAMPhi, arginase activity and collagen deposition
      in the peritoneal membrane. Treatment with the arginase inhibitor or
      supplementation with l-arginine did not change the parasitic load or profile of
      the infection. However, the arginase inhibitor significantly decreased the
      deposition of collagen. These results suggest that arginase activity does not
      interfere with parasite control during experimental infection with T. crassiceps,
      but it is important for fibrosis in cysticercosis. 

PMID- 24090571
TI  - Both LCCL-domains of human CRISPLD2 have high affinity for lipid A.
AB  - The LCCL-domain is a recently defined protein module present in diverse
      extracellular multidomain proteins. Practically nothing is known about the
      molecular function of these domains; based on functional features of proteins
      harboring LCCL-domains it has been suggested that these domains might function as
      lipopolysaccharide-binding domains. Here we show that the two LCCL-domains of
      human CRISPLD2 protein, a lipopolysaccharide-binding serum protein involved in
      defense against endotoxin shock, have higher affinity for the lipid A, the toxic
      moiety of lipopolysaccharides than for ipopolysaccharide. Our observation that
      the LCCL-domains of CRISPLD2 are specific for the toxic lipid A moiety of the
      endotoxin suggests that it may block the interaction between endotoxins and the
      host endotoxin receptors without interfering with the development of
      antibacterial immunity against the polysaccharide moiety of LPS. We suggest that
      the anti-inflammatory function of CRISPLD2 protein may account for its role in
      various pathological and developmental processes. 

PMID- 24090572
TI  - [A rib lesion].

PMID- 24090573
TI  - [Cardiac amyloidosis: a case series of 14 patients, description and prognosis].
AB  - PURPOSE: Cardiac amyloidosis is rare. The objective of this study was to report
      on a case series of 14 patients with cardiac amyloidosis and to study the
      prognostic factors. METHODS: Monocentric retrospective study of all adult
      patients who presented with cardiac amyloidosis, diagnosed at the Georges
      Pompidou European hospital in Paris between 2003 and 2011. RESULTS: Fourteen
      patients were identified (10 men and four women). Median age at diagnosis was
      66.5 years. Twelve patients were diagnosed with AL amyloidosis, one with AA
      amyloidosis, and one with transthyretin amyloidosis. All patients presented
      cardiac manifestations: heart failure (n=9), rhythm disorders (n=6). Eight
      patients presented extra-cardiac manifestations of amyloidosis: renal (n=8),
      gastrointestinal (n=5). Troponin serum level was increased in eight patients and
      BNP level was superior to 400 pg/L in 12 patients. When performed, the cardiac
      magnetic resonance imaging (MRI) showed, in six patients out of seven, chamber
      dilatation, concentric hypertrophy or late enhancement. Among patients with
      cardiac failure at diagnosis (n=9), seven died with a median survival of 1 month
      duration. Factors of poor prognosis were, in our study, heart failure, elevated
      levels of troponin and BNP, and the AL amyloidosis subtype. CONCLUSION: Cardiac
      amyloidosis, especially the AL type, has a very poor prognosis, essentially
      because of an underlying multiple myeloma and heart failure.

PMID- 24090574
TI  - "Boot camp" simulator training in open hilar dissection in early cardiothoracic
      surgical residency.
AB  - BACKGROUND: We evaluated focused training in lung hilar dissection with a
      reanimated porcine lung model in the boot camp setting. METHODS: A total of 64
      first-year cardiothoracic surgical residents participated in four consecutive
      hours devoted to training in open hilar dissection as part of the Thoracic
      Surgical Directors Association boot camps. Each resident participated in two open
      hilar dissections. Component tasks were assessed on a 5-point rating scale for
      the first and second dissections. RESULTS: Immediate assessment performed after
      completion of the session showed improvements in all graded components. The mean
      total score on a 50-point scale improved significantly between the first and
      second repetition (36.03 +/- 7.03 to 41.16 +/- 6.95; p = 0.001). CONCLUSIONS:
      Focused massed (single-session) practice in the boot camp setting improved the
      ability of residents to perform hilar dissection on simulators using reanimated
      porcine lung models. Given these early successes in massed simulation-based
      surgical education, there is good reason to expect that deliberate and
      distributed practice on similar simulators would improve resident education in
      cardiothoracic surgery.

PMID- 24090575
TI  - The Impella device for acute mechanical circulatory support in patients in
      cardiogenic shock.
AB  - BACKGROUND: Acute cardiogenic shock is associated with high mortality rates.
      Mechanical circulatory devices have been increasingly used in this setting for
      hemodynamic support. The Impella device (Abiomed Inc, Danvers, MA) is a
      microaxial left ventricular assist device that can be inserted using a less
      invasive technique. This study was conducted to determine the outcome of patients
      who have undergone placement of the Impella device for acute cardiogenic shock in
      our institution. METHODS: A retrospective record review of 47 patients who
      underwent placement of the Impella device was performed from January 1, 2006, to
      December 31, 2011. Records were evaluated for demographics, operative details,
      and postoperative outcomes. Operative mortality was defined as death within 30
      days of the operation. RESULTS: The patients (33 male) were an average age of
      60.23 +/- 13 years. The indication for placement of the Impella device included
      cardiogenic shock in 15 patients (32%) and postcardiotomy cardiogenic shock in 32
      (68%). Of the 47 patients, 38 (80%) received the Impella 5.0 and the rest the 2.5
      device. Ventricular function recovered in 34 of 47 patients (72%), and the device
      was removed, with 4 patients (8%) transitioned to long-term ventricular assist
      devices. The 30-day mortality was 25% (12 of 47 patients). Complications occurred
      in 14 patients (30%), consisting of device malfunction, high purge pressures,
      tube fracture, and groin hematoma. CONCLUSIONS: This is one of the largest series
      of patients undergoing placement of the Impella device for acute cardiogenic
      shock. Our outcomes showed improved results compared with historical data.
      Myocardial recovery was accomplished in most patients. Finally, the 30-day
      mortality and complication rate was acceptable in these critical patients. These
      benefits were all achieved with the Impella device in a less invasive method.

PMID- 24090576
TI  - Statistical assessment of normal mitral annular geometry using automated three
      dimensional echocardiographic analysis.
AB  - BACKGROUND: The basis of mitral annuloplasty ring design has progressed from
      qualitative surgical intuition to experimental and theoretical analysis of
      annular geometry with quantitative imaging techniques. In this work, we present
      an automated three-dimensional (3D) echocardiographic image analysis method that
      can be used to statistically assess variability in normal mitral annular geometry
      to support advancement in annuloplasty ring design. METHODS: Three-dimensional
      patient-specific models of the mitral annulus were automatically generated from
      3D echocardiographic images acquired from subjects with normal mitral valve
      structure and function. Geometric annular measurements including annular
      circumference, annular height, septolateral diameter, intercommissural width, and
      the annular height to intercommissural width ratio were automatically calculated.
      A mean 3D annular contour was computed, and principal component analysis was used
      to evaluate variability in normal annular shape. RESULTS: The following mean +/-
      standard deviations were obtained from 3D echocardiographic image analysis:
      annular circumference, 107.0 +/- 14.6 mm; annular height, 7.6 +/- 2.8 mm;
      septolateral diameter, 28.5 +/- 3.7 mm; intercommissural width, 33.0 +/- 5.3 mm;
      and annular height to intercommissural width ratio, 22.7% +/- 6.9%. Principal
      component analysis indicated that shape variability was primarily related to
      overall annular size, with more subtle variation in the skewness and height of
      the anterior annular peak, independent of annular diameter. CONCLUSIONS: Patient
      specific 3D echocardiographic-based modeling of the human mitral valve enables
      statistical analysis of physiologically normal mitral annular geometry. The tool
      can potentially lead to the development of a new generation of annuloplasty rings
      that restore the diseased mitral valve annulus back to a truly normal geometry.

PMID- 24090577
TI  - Open, video-assisted thoracic surgery, and robotic lobectomy: review of a
      national database.
AB  - BACKGROUND: To date, reports on outcomes after robotic-assisted pulmonary
      resection have been confined to small, single-institution case series.
      Furthermore, no comparison has been made between robotic, open, and video
      assisted thoracic surgery (VATS) procedures. We sought to compare the outcomes
      between these approaches using the State Inpatient Databases (SID). METHODS:
      Using the 2008 to 2010 SID, we identified patients who underwent an open, VATS,
      or robotic lobectomy from 8 states. Patients who underwent segmentectomy were
      also included. A comparison of outcomes was performed using a propensity-matched
      analysis. RESULTS: We identified a total of 33,095 patients (open: 20,238; VATS:
      12,427; robotic: 430). Case volumes for robotic resections increased over the
      study period from 0.2% in 2008 to 3.4% in 2010. Robotic resections were performed
      in all 8 states, and 38% were conducted in a community hospital. In propensity
      matched analysis, robotic resections were associated with significant reductions
      in mortality (0.2% vs 2.0%, p = 0.016), length of stay (5.9 vs 8.2 days, p <
      0.0001), and overall complication rates (43.8% vs 54.1%, p = 0.003) when compared
      with open thoracotomy. Robotic resection was also associated with reductions in
      mortality (0.2% vs 1.1%, p = 0.12), length of stay (5.9 days vs 6.3 days, p =
      0.45), and overall complication rates (43.8% vs 45.3%, p = 0.68) when compared
      with VATS; however, none of these differences were statistically significant.
      CONCLUSIONS: Case volume for robotic pulmonary resections has increased
      significantly during the study period, and thoracic surgeons have been able to
      adopt the robotic approach safely. Robotic resection appears to be an appropriate
      alternative to VATS and is associated with improved outcomes compared with open
      thoracotomy.

PMID- 24090578
TI  - Red blood cell storage: how long is too long?
AB  - Red blood cells (RBCs) undergo biochemical and structural changes during storage,
      commonly referred to as the "storage lesion." Evidence suggests that the longer
      the RBC product is stored, the less effective is the transfused blood. Many
      studies linking morbidity to transfusion have not considered duration of RBC
      storage as a variable that may modulate the effect. In addition, the effects of
      supply and demand and RBC inventory management strategies have been incompletely
      investigated. It is possible to envision a blood management system based on
      modern inventory management strategies that could greatly reduce storage
      duration. 

PMID- 24090579
TI  - Failure-to-rescue rate as a measure of quality of care in a cardiac surgery
      recovery unit: a five-year study.
AB  - BACKGROUND: Failure to rescue, which is defined as the probability of death after
      a complication that was not present on admission, was introduced as a quality
      measure in the 1990s, to complement mortality and morbidity outcomes. The
      objective of this study was to evaluate possible incremental benefits of
      measuring failure to rescue after cardiac surgery, to facilitate quality
      improvement efforts. METHODS: Data were collected prospectively on 4,978
      consecutive patients who underwent cardiac operations during a 5-year period.
      Institutional logistic regression models were used to generate predicted rates of
      mortality and major complications. Frequency distributions of morbidities were
      determined, and failure to rescue was calculated. The annual failure-to-rescue
      rates were contrasted using chi(2) tests and compared with morbidity and
      mortality measures. RESULTS: The overall mortality rate was 3.6%, the total
      complication rate was 16.8%, and the failure-to-rescue rate was 19.8% (95%
      confidence interval, 17.1% to 22.7%). The predicted risk of mortality and of
      major complications increased during the last 2 years of the study, whereas the
      observed complication rate decreased. Failure to rescue for new renal failure was
      the highest of all complications (48.4%), followed by septicemia (42.6%). Despite
      the decreased complication rate toward the end of the study, the failure-to
      rescue rate did not change significantly (p = 0.28). CONCLUSIONS: Failure to
      rescue should be monitored as a quality-of-care metric, in addition to mortality
      and complication rates. Postoperative renal failure and septicemia still have a
      high failure-to-rescue rate and should be targeted by quality improvement
      efforts.

PMID- 24090580
TI  - The radial artery: current concepts on its use in coronary artery
      revascularization.
AB  - The radial artery (RA) can be used as part of an arterial revascularization
      strategy in coronary artery bypass grafting (CABG). It is easy to harvest and
      several randomized controlled trials and meta-analyses have reported superior
      long-term patency over saphenous vein grafts. However, the RA is not used as
      frequently as the saphenous vein and questions remain regarding its optimum use
      as a conduit. This article comprehensively appraises current evidence surrounding
      outcomes, patient selection, harvesting technique, intraoperative strategy, and
      graft spasm prophylaxis to provide a contemporary review of the use of the RA as
      a conduit in CABG.

PMID- 24090581
TI  - Meta-analysis of staged versus combined carotid endarterectomy and coronary
      artery bypass grafting.
AB  - BACKGROUND: The multiple options in the management of patients with concomitant
      carotid and coronary artery disease (CAD) make it difficult to find a clear
      consensus regarding the ideal surgical strategy. We performed a meta-analysis of
      studies comparing early outcomes of synchronous and staged approach of carotid
      endarterectomy and coronary artery bypass grafting. METHODS: All English language
      publications were searched using the terms "carotid artery disease," "coronary
      artery disease," "carotid endarterectomy," and "coronary artery bypass grafting"
      alone or in combination. The endpoints studied were early mortality, major
      stroke, and major postoperative morbidity; myocardial infarction (MI) and stroke,
      and combined early mortality or stroke. Early events were compared using pooled
      estimates of risk ratios (RR) (random effects model) utilizing the inverse
      variance method. RESULTS: Twelve studies were identified with a total of 17,469
      and 7,552 patients in the combined and staged group, respectively. The pooled
      analysis revealed no difference in the early mortality (RR 1.36 [0.78, 2.36]; p =
      0.27), post operative stroke (RR 1.14 [0.99, 1.31], p = 0.07), combined early
      mortality or stroke (RR 1.08 [0.98, 1.20], p = 0.11) and combined endpoint of MI
      or stroke (RR 0.75 [0.48, 1.17; I(2) = 11%], p = 0.2) between the 2 surgical
      approaches. CONCLUSIONS: Our meta-analysis of observational studies suggests
      comparable outcomes in combined and staged approach for synchronous carotid and
      coronary artery disease. Hence, the 2 strategies can be used interchangeable in
      the clinical practice, with each having specific applications linked to specific
      clinical conditions. A randomized trial is warranted to answer this question
      definitively.

PMID- 24090582
TI  - Physician assistant model for lung procurements: a paradigm worth considering.
AB  - BACKGROUND: Thoracic procurements have traditionally been performed by surgical
      fellows or attending cardiothoracic surgeons. Donor lung procurement protocols
      are well established and fairly standardized; however, specific procurement
      training and judgment are essential to optimizing donor utilization. Although the
      predicted future deficits of cardiothoracic surgeons are based on a variety of
      analytic models and scenarios, it appears evident that there will not be a
      sufficient number of trained cardiothoracic surgeons over the next 2 decades.
      Over the past 5 years in our institution, lung procurements have been performed
      by a specifically trained physician assistant; as the lead donor surgeon. This
      model may serve as a cost effective, reproducible, and safe alternative to using
      surgical fellows and attending surgeons, assuring continuity, ongoing technical
      expertise, and teaching while addressing future workforce issues as related to
      transplant. METHODS: This is a single institution review of 287 consecutive lung
      procurements performed by either a physician assistant or fellow over 5 years.
      This study was approved by the Institutional Review Board of Columbia University,
      which waived the need for informed consent (IRB#AAAL7107). RESULTS: From 2008 to
      2012, fellows served as senior surgeon in 90 cases (31.4%) versus 197 cases
      (68.6%) by the physician assistant, including 12 Donations after Cardiac Death
      and 6 reoperative donors. Injury rate was significantly lower for the physician
      assistant compared with the resident cohort (1 of 197 [0.5%] vs 22 of 90 [24%],
      respectively). Rates for pulmonary graft dysfunction grade 2 and 3 were found to
      be significantly lower in cases where the physician assistant served as senior
      surgeon (combined rates of 32.2% [29 of 90] vs 9.6% [19 of 197] in the physician
      assistant group) (p < 0.01). CONCLUSIONS: Use of experienced physician assistants
      in donor lung procurements is a safe and viable alternative offering continuity
      of technical expertise and evaluation of lung allografts.

PMID- 24090583
TI  - Fasting-induced increase in plasma ghrelin is blunted by intravenous alcohol
      administration: a within-subject placebo-controlled study.
AB  - Ghrelin is a 28-amino acid peptide produced mainly by mucosal neuroendocrine
      cells lining the fundus of the stomach. Preclinical and clinical studies suggest
      that ghrelin plays a role in alcoholism. Furthermore, human laboratory studies
      indicate that acute oral administration of alcohol results in reduced circulating
      ghrelin. As ghrelin is primarily produced in the stomach, one question never
      previously explored is whether alcohol administered intravenously (IV) results in
      similar decrease in ghrelin levels. Thus, this study analyzed the potential
      effects of IV alcohol administration on plasma ghrelin levels in healthy
      nonsmoking social drinkers (n=44) who received either a 180-min IV infusion of 6%
      (v/v) alcohol or 0.9% normal saline in two separate counterbalanced sessions. At
      each session, participants arrived having fasted for ~7 h and received a light
      breakfast 60 min before the infusion. The percent change (%Delta) in ghrelin
      levels was 4.5-fold less in the alcohol condition than the saline condition. In
      fact, there was only a modest change in ghrelin levels from baseline in the IV
      alcohol condition (9.6%Deltaghrelin) while in the IV saline condition there was a
      robust change (43.4%Deltaghrelin). There was a trend toward significance in
      %Deltaghrelin in the alcohol condition compared to the placebo condition
      (F[1,33]=3.3, p=0.07). While the exact mechanisms by which alcohol influences
      ghrelin levels are unclear, alcohol may act directly in the stomach by inhibiting
      ghrelin secretion and/or release, and may also attenuate ghrelin levels
      systemically. Although IV alcohol did not reduce circulating ghrelin levels, as
      seen in previous studies with oral alcohol administration, the present findings
      suggest that, despite bypassing the stomach, alcohol still attenuated circulating
      ghrelin levels, i.e. the fasting-induced increase in circulating ghrelin was
      blunted by IV alcohol administration. These findings lead us to hypothesize that
      alcohol might affect ghrelin signaling not only via a local effect on the stomach
      mucosa, but also via a systemic effect.

PMID- 24090584
TI  - Estrogen-progesterone balance in the context of blastocyst implantation failure
      induced by predator stress.
AB  - Diverse stressors can disrupt blastocyst implantation in inseminated female
      mammals. Stress-induced implantation failure can be mimicked by minute doses of
      exogenous estradiol, and some evidence indicates that it may be mitigated by
      exogenous progesterone. In Experiment 1, we showed that acute exposure to a rat
      across a wire-mesh grid caused elevation of corticosterone and progesterone. In
      Experiment 2, we showed that exposure of inseminated mice to rats across a grid
      during gestation days 1-5 was associated with avoidance of proximity to the grid
      and a significantly reduced number of implantation sites on gestation day 6. Rat
      exposure also resulted in elevated progesterone levels in females that maintained
      their pregnancies, and elevated estradiol levels in females that lost their
      pregnancies. In Experiment 3, we investigated whether exogenous progesterone,
      estradiol, or a combination of both could influence implantation failure induced
      by rat-exposure stress. Treatment with 100 ng estradiol per day on gestation days
      1-5 induced a complete absence of implantation sites on gestation day 6,
      regardless of the presence or absence of the stressor. Administration of 500 MUg
      progesterone per day was insufficient to prevent the stress-induced pregnancy
      loss. However, 500 MUg progesterone plus 10 ng estradiol per day did prevent
      implantation failure in rat-exposed females. These findings are consistent with
      the hypothesis that estradiol elevations contribute to stress-induced pregnancy
      loss, but show paradoxically that low doses of estradiol can act together with
      progesterone to mitigate stress-induced pregnancy loss.

PMID- 24090585
TI  - Prenatal stress, partner support, and infant cortisol reactivity in low-income
      Mexican American families.
AB  - Maternal exposure to significant prenatal stress can negatively affect infant
      neurobiological development and increase the risk for developmental and health
      disturbances. These effects may be pronounced in low SES and ethnic minority
      families. We explored prenatal partner support as a buffer of the impact of
      prenatal stress on cortisol reactivity of infants born to low-income Mexican
      American women. Women (N=220; age 18-42; 84% Spanish-speaking; 89% foreign born;
      modal family income $10,000-$15,000) reported on economic stress and satisfaction
      with spousal/partner support during the prenatal period (26-38 weeks gestation),
      and infant salivary cortisol reactivity to mildly challenging mother-infant
      interaction tasks was assessed at women's homes at six weeks postpartum.
      Multilevel models estimated the interactive effect of prenatal stress and partner
      support on cortisol reactivity, controlling for covariates and potential
      confounds. Infants born to mothers who reported high prenatal stress and low
      partner support exhibited higher cortisol reactivity relative to those whose
      mothers reported high support or low stress. The effects did not appear to
      operate through birth outcomes. For low-income Mexican American women, partner
      support may buffer the impact of prenatal stress on infant cortisol reactivity,
      potentially promoting more adaptive infant health and development. 

PMID- 24090586
TI  - [Influence of vitamin D on cardiovascular risk].
AB  - Few interventional studies have reported a positive effect of native vitamin D
      supplementation on intermediary parameters of insulin resistance, of
      cardiovascular risk and on major cardiovascular events and mortality. 

PMID- 24090587
TI  - Emerging injectable therapies for multiple sclerosis.
AB  - Available treatment options for relapsing-remitting multiple sclerosis (MS) have
      expanded in recent years, and several injectable therapies are under development.
      In this Rapid Review, we summarise emerging injectable therapies for relapsing
      remitting MS, and discuss pharmacological mechanisms, clinical trials, adverse
      events, and use in clinical practice. Many new potential treatments for MS are at
      an intermediate to advanced stage of development. Alemtuzumab is a monoclonal
      antibody that has shown efficacy in phase 3 trials but, because of serious
      adverse events associated with this drug, clinical monitoring is essential.
      Pegylated interferon beta-1a has shown efficacy in a phase 3 trial. Daclizumab
      and ocrelizumab are monoclonal antibodies that have shown efficacy and acceptable
      safety profiles in phase 2 trials; both are under investigation in ongoing phase
      3 trials. Ofatumumab is a monoclonal antibody that has shown efficacy in a small
      phase 2 trial. Animal models suggest that anti-LINGO1 antibody has remyelinating
      potential, and phase 2 trials of the antibody are underway. Further clarification
      of purported mechanisms of action and continued surveillance will be essential to
      establish the safety and clinical efficacy of these drugs in patients with
      relapsing-remitting MS. 

PMID- 24090588
TI  - Simvastatin for cognitive deficits and behavioural problems in patients with
      neurofibromatosis type 1 (NF1-SIMCODA): a randomised, placebo-controlled trial.
AB  - BACKGROUND: Neurofibromatosis type 1 is a common genetic disorder characterised
      by neurocutaneous manifestations and cognitive and behavioural problems. Statins
      were shown to reduce analogous learning deficits in a mouse model of the disease,
      but a short-term trial in humans was inconclusive. We aimed to assess the use of
      simvastatin for the improvement of cognitive and behavioural deficits in children
      with neurofibromatosis type 1 for 12 months. METHODS: In this randomised, double
      masked, placebo-controlled trial, we recruited children with genetically
      confirmed neurofibromatosis type 1 aged 8-16 years from two national referral
      centres in the Netherlands and Belgium. Those with symptomatic CNS abnormalities
      or on neurotropic medication, including stimulants, were excluded. Eligible
      patients were randomly assigned (1:1) via a computer-generated, permuted-block
      list to simvastatin (10 mg per day in month 1, 20 mg per day in month 2, and 20
      40 mg per day in months 3-12) or placebo for 12 months. Investigators,
      participants, and parents were masked to treatment assignment. Primary outcome
      measures were full-scale intelligence (Wechsler intelligence scale for children),
      attention problems (child behaviour checklist, parent-rated [CBCL]), and
      internalising behavioural problems (CBCL). We did intention-to-treat analyses (of
      all patients who had outcome data) using linear regression of the 12 month
      outcome scores, adjusted for baseline performance. This trial is registered with
      the Netherlands Trial Register, number NTR2150. FINDINGS: We randomly assigned 84
      children to a treatment group (43 to simvastatin, 41 to placebo) between March 9,
      2010, and March 6, 2012. We did not assess outcomes in two patients in the
      placebo group because they needed additional drug therapy. Simvastatin for 12
      months had no effect on full-scale intelligence (treatment effect compared with
      placebo -1.3 IQ points [95% CI -3.8 to 1.3]; p=0.33), attention problems (-1.6 T
      score points [-4.3 to 1.0]; p=0.23), and internalising behavioural problems (-0.1
      T-score points [-3.3 to 3.1]; p=0.96). 38 (88%) of 43 patients on simvastatin and
      39 (95%) of 41 patients on placebo reported adverse events, which were serious in
      two and four patients, respectively. INTERPRETATION: 12 month simvastatin
      treatment did not ameliorate cognitive deficits or behavioural problems in
      children with neurofibromatosis type 1. The use of 20-40 mg simvastatin per day
      for cognitive enhancement in children with neurofibromatosis type 1 is not
      recommended. FUNDING: The Netherlands Organization for Health Research and
      Development (ZonMw), Research Foundation Flanders (FWO-Vlaanderen), Marguerite
      Marie Delacroix Foundation, and the Dutch Neurofibromatosis Association (NFVN).

PMID- 24090589
TI  - Claudia Trenkwalder: from bench to bedside (and back again). Interview by Dara
      Mohammadi.

PMID- 24090590
TI  - A long shot? Could neurodegenerative disease be caused by a cyanobacterial toxin?

PMID- 24090592
TI  - Effect of bisphenol A on pluripotency of mouse embryonic stem cells and
      differentiation capacity in mouse embryoid bodies.
AB  - Bisphenol A (BPA) poses potential risks to reproduction and development. However,
      the mechanism of BPA's effects on early embryonic development is still unknown.
      Embryonic stem cells (ESC) and embryoid bodies (EB) provide valuable in vitro
      models for testing the toxic effects of environmental chemicals in early
      embryogenesis. In this study, mouse embryonic stem cells (mESC) were acutely
      exposed to BPA for 24h, and general cytotoxicity and the effect of BPA on
      pluripotency were then evaluated. Meanwhile, mouse embryoid bodies (mEB) were
      exposed to BPA up to 6 days and their differentiation capacity was evaluated. In
      mESC and mEB, we found that BPA up-regulated pluripotency markers (Oct4, Sox2 and
      Nanog) at mRNA and/or protein levels. Moreover, BPA increased the mRNA levels of
      endodermal markers (Gata4,Sox17) and mesodermal markers (Sma,Desmin), and reduced
      the mRNA levels of ectodermal markers (Nestin,Fgf5) in mEB. Furthermore,
      microRNA(miR)-134, an expression inhibitor of pluripotency markers including
      Oct4, Sox2 and Nanog, was decreased both in BPA-treated mESC and mEB. These
      results firstly indicate that BPA may disturb pluripotency in mESC and
      differentiation of mEB, and may inhibit ectodermal lineage differentiation of mEB
      while miR-134 may play a key role underlying this effect.

PMID- 24090593
TI  - Hematopoietic stem cell expansion caused by a synthetic fragment of leptin.
AB  - Leptin is a cytokine that regulates food intake, energy expenditure and
      hematopoiesis. Based on the tridimensional structure of the human leptin
      molecule, six fragments have been synthesized, (Ac-Lep23-47-NH2, [LEP1]; Ac-Lep48
      71-NH2, [LEP2]; Ac-Lep72-88-NH2, [LEP3]; Ac-Lep92-115-NH2, [LEP4], Ac-[Ser(117)]
      Lep116-140-NH2, [LEP5] and Ac-Lep141-164-NH2, [LEP6]), and their effects on
      hematopoiesis were evaluated. The mice were treated with 1mg/kg LEP5 for 3 days.
      The mature and primitive hematopoietic populations were quantified. We observed
      that the mature populations from the bone marrow and spleen were not affected by
      LEP5. However, the peptide caused at least a two-fold increase in the number of
      hematopoietic stem cells, the most primitive population of the bone marrow.
      Additionally, the number of granulocyte/macrophage colony-forming units produced
      by bone marrow cells in methylcellulose also increased by 40% after treatment
      with LEP5, and the leptin receptor was activated. These results show that the
      leptin fragment LEP5 is a positive modulator of the in vivo expansion of
      hematopoietic stem cells. 

PMID- 24090594
TI  - Antimicrobial resistance and integrons of commensal Escherichia coli strains from
      healthy humans in China.

PMID- 24090595
TI  - Preparation of titanium-grafted magnetic mesoporous silica for the enrichment of
      endogenous serum phosphopeptides.
AB  - As one of the most important post-translational modifications, reversible
      phosphorylation of protein plays crucial roles in a large number of biological
      processes. Moreover, endogenous phosphopeptides are also associated with certain
      human diseases. An efficient enrichment and separation method is the premise for
      successful identification and quantification of phosphopeptides. In this work,
      titanium grafted magnetic mesoporous silica (Fe3O4@Ti-mSiO2) was developed and
      applied for the enrichment of endogenous phosphopeptides. Fe3O4@Ti-mSiO2
      particles were prepared by grafting titanocene dichloride on the inner walls of
      magnetic mesoporous silica and then being calcined to remove cyclopentadienyl
      ligand. The physicochemical properties of the prepared materials were
      characterized by energy dispersive X-ray spectroscopy (EDX), nitrogen adsorption
      desorption analysis, X-ray diffraction (XRD), transmission electron microscopy
      (TEM), scanning electron microscopy (SEM) and vibrating sample magnetometer
      (VSM). For selective enrichment of phosphopeptides, the prepared Fe3O4@Ti-mSiO2
      particles were applied for tryptic digests of beta-casein, mixtures of beta
      casein and bovine serum albumin (BSA), and low-fat milk. Finally, Fe3O4@Ti-mSiO2
      was successfully applied for the enrichment of endogenous phosphopeptides from
      human serum.

PMID- 24090596
TI  - The separation of flavonoids from Pongamia pinnata using combination columns in
      high-speed counter-current chromatography with a three-phase solvent system.
AB  - The mangrove plant Pongamia pinnata (Leguminosae) is well known as a plant
      pesticide. Previous studies have indicated that the flavonoids are responsible of
      the biological activities of the plant. A new high-speed counter-current
      chromatography (HSCCC) method for the separation of three flavonoids, karanjin
      (1), pinnatin (2), and pongaflavone (3), from P. pinnata was developed in the
      present study. The lower and intermediate phase (LP and IP) of a new three-phase
      solvent system, n-hexane-acetonitrile-dichloromethane-water, at a volume ratio of
      5:5:1:5, were used as the stationary phases, while the upper phase (UP) was used
      as the mobile phase, and the volume ratio between the stationary phases in the
      CCC column could be tuned by varying the initial pumped volume ratio of the
      stationary phases. The CCC columns containing all three phases of the solvent
      system were considered combination columns. According to the theories of
      combination column, it is possible to optimize the retention time of the target
      compounds by varying the volume ratio of the stationary phases in the HSCCC
      combination columns, as well as the suitable volume ratios of the stationary
      phases for the separation of the target compounds were predicted from the
      partition coefficients of the compounds in the three-phase solvent system. Then,
      three HSCCC separations using the combination columns with initial pumped LP:IP
      volume ratios of 1:0, 0.9:0.1, and 0.7:0.3 were performed separately based on the
      prediction. Three target compounds were prepared with high purity when the
      initial pumped volume ratio of the stationary phases was 0.9:0.1. The baseline
      separation of compounds 2 and 3 was achieved on the combination column with an
      initial pumped volume ratio of 0.7:0.3. Furthermore, the three experiments
      clearly demonstrated that the retentions and resolutions of the target compounds
      increased with an increasing volume ratio of IP, which is consistent with the
      prediction for the retention times for the solutes on combination columns. The
      method proposed here reduces the need for solvent selection compared with the
      conventional method and may have broad potential applicability in the preparation
      of natural products.

PMID- 24090597
TI  - Impact of graft-versus-host disease on allogeneic hematopoietic cell
      transplantation for adult T cell leukemia-lymphoma focusing on preconditioning
      regimens: nationwide retrospective study.
AB  - Allogeneic hematopoietic cell transplantation (HCT), but not autologous HCT, can
      provide long-term remission in some patients with adult T cell leukemia-lymphoma
      (ATL). We retrospectively analyzed the effects of acute graft-versus-host disease
      (GVHD) among the 616 patients with ATL who survived at least 30 days after
      allogeneic HCT with other than cord blood grafts. Multivariate analyses treating
      the occurrence of GVHD as a time-varying covariate demonstrated an association
      between grade I-II acute GVHD and favorable overall survival (OS) (hazard ratio
      [HR], 0.634; 95% confidence interval [CI], 0.477 to 0.843), whereas grade III-IV
      acute GVHD showed a trend toward unfavorable OS (HR, 1.380; 95% CI, 0.988 to
      1.927) compared with nonacute GVHD. In subsequent multivariate analyses of
      patients who survived at least 100 days after HCT (n = 431), the presence of
      limited chronic GVHD showed a trend toward favorable OS (HR, 0.597; 95% CI, 0.354
      to 1.007), and extensive chronic GVHD had a significant effect on OS (HR, 0.585;
      95% CI, 0.389 to 0.880). There were no significant interactions between
      myeloablative conditioning or reduced-intensity conditioning with OS even when
      acute GVHD was absent or present at grade I-II or grade III-IV or when chronic
      GVHD was absent, limited, or extensive. This study demonstrates the actual
      existence of graft-versus-ATL effects in patients with ATL regardless of whether
      myeloablative conditioning or reduced-intensity conditioning is used.

PMID- 24090599
TI  - Current concepts of contrast-induced nephropathy: a brief review.
AB  - Contrast-induced nephropathy (CIN) is a common hospital-acquired acute kidney
      injury. Published studies on this condition have dramatically increased in recent
      years. This article aims to provide a brief literature review. English articles
      published from 1983 to 2012 were retrieved from PubMed by searching using the
      term "contrast-induced nephropathy." Patients with CIN were associated with
      increased resource utilization, prolonged hospital stay, and increased long-term
      mortality. CIN is defined as a >= 0.5 mg/dL rise in serum creatinine or a 25%
      increase, assessed within 48-72 hours after administration of contrast medium
      (CM). All patients receiving CM should be evaluated for their CIN risk,
      especially preexisting kidney disease. The CM should be prewarmed to 37  degrees
      C and injected at the lowest possible dose. Repeat injection within 72 hours
      should be avoided. Either iso-osmolar CM or low-osmolar CM, except ioxaglate or
      iohexol, can be used in all patients. Iso-osmolar CM iodixanol may be a better
      choice for high-risk patients with chronic kidney disease requiring intra
      arterial administration. Nephrotoxic drugs should be stopped 2 days prior to when
      the patient undergoes a procedure. All patients receiving CM should be at an
      optimal volume status. Parenteral isotonic saline without any diuretic should be
      started 12 hours prior to CM at a rate of 1 mL/kg/h and continued for 24 hours if
      there is no contraindication. In patients who require shorter volume supplement
      periods or are at a higher risk, bicarbonate infusion (154 mEq/L, 3 mL/kg/h for 1
      hour bolus prior to CM, followed by 1 mL/kg/h for 6 hours) may be used as an
      alternative to isotonic saline. Oral N-acetylcysteine (600 mg bid, starting on
      the day prior to the procedure) together with parenteral hydration is suggested
      for patients at risk. Hemodialysis/hemofiltration is only considered in chronic
      kidney disease stage 4/5 patients when an access is available. The other
      medications or techniques for reducing CIN risk are still unclear. CIN is a
      potentially preventable clinical condition. A careful review of published reports
      gives us a deeper understanding of CIN and a greater chance of decreasing its
      risk.

PMID- 24090598
TI  - Myeloablative cord blood transplantation in adults with acute leukemia:
      comparison of two different transplant platforms.
AB  - We compared the clinical outcomes of adults with acute leukemia that received
      single-unit umbilical cord blood transplantation (sUCBT) after conditioning with
      a busulfan/antithymocyte globulin (BU-ATG)-based regimen at University Hospital
      La Fe (n = 102) or double-unit UCBT (dUCBT) after conditioning with a total body
      irradiation (TBI)-based regimen at the University of Minnesota (n = 91).
      Nonrelapse mortality, relapse and disease-free survival were similar in the 2
      groups. Multivariate analyses, showed more rapid neutrophil (hazard ratio [HR],
      .6; 95% confidence interval [CI], .45 to .80; P = .0006) and platelet recovery
      (HR, .59; 95% CI, .43 to.83; P = .002) after the BU-ATG-based conditioning and
      sUCBT. Although there was a lower risk of acute graft-versus-host disease (GVHD)
      grade II to IV (HR, 2.81; 95% CI, 1.75 to 4.35; P < .001) after BU-ATG and sUCBT,
      the incidences of grade III to IV acute and chronic GVHD were similar between the
      2 groups. Regarding disease-specific outcomes, disease-free survival in both
      acute myeloid leukemia and acute lymphoblastic leukemia (ALL) patients were not
      significantly different; however, a significantly lower relapse rate was found in
      patients with ALL treated with TBI and dUCBT (HR, .3; 95% CI, .12 to .84; P =
      .02). In the context of these specific treatment platforms, our study
      demonstrates that sUCB and dUCBT offer similar outcomes.

PMID- 24090600
TI  - One-year results of transcatheter aortic valve implantation as an alternative
      treatment for severe aortic stenosis in high-risk patients.
AB  - BACKGROUND: Aortic valve replacement (AVR) remains the gold standard treatment
      for symptomatic severe aortic stenosis (AS). For the past 10 years, transcatheter
      aortic valve implantation (TAVI) has been applied in patients with high surgical
      mortality and morbidity risks. The preliminary results of our TAVI patients are
      presented in this study. METHODS: Ten high-risk patients with severe AS, for AVR,
      were referred and accepted for TAVI in the 6 month period from May 2010 to
      October 2010. The patient age, logistic EuroSCORE, femoral arterial diameter,
      aorta annulus size, aorta valve area (AVA), mean aortic pressure gradient (MPG),
      as well as coronary angiography results were all collected. Six patients were
      treated via the transapical approach in March 2010, whereas the other four were
      treated with the transfemoral approach, according to their femoral artery
      diameter and arterial quality. This study focuses on the immediate, 1 month, 3
      month, and 1 year results of TAVI. RESULTS: The average age of the 10 patients
      receiving TAVI was 81.5 years. The mean calculated EuroSCORE was 28.3 +/- 7.9%.
      The mean AVA was 0.61 +/- 0.19 cm(2). The MPG was 48 +/- 16 mmHg. The surgical
      technical success achieved 100%. There was no reported moderate to severe
      postoperative paravalvular aortic regurgitation, permanent complete
      atrioventricular block, major access site complication, or embolic stroke.
      Chronic renal failure, which necessitated permanent hemodialysis, developed in
      10% of the patients. One acute myocardial infarction and one case of pneumonia
      developed postoperatively. The AVA was increased by 251%, whereas the MPG was
      decreased by 80% at the 3 month follow-up. The 30-day mortality rate was 10%. The
      all-cause 1-year mortality rate was 20%. CONCLUSION: This new technique and
      device requires greater caution and needs more practice to accumulate sufficient
      experience. The studied patients were very fragile, due to old age and multiple
      comorbidities. Our results are similar to findings of multicenter trials. With
      careful patient screening and selection, TAVI can be a promising treatment for
      high-risk severe AS patients.

PMID- 24090601
TI  - Spinal microglia: A potential target in the treatment of chronic visceral pain.
AB  - Chronic visceral pain is the predominant symptom of functional gastrointestinal
      disorders and chronic pancreatitis. Such pain can impair the patients' quality of
      life, and can also serve as one of the principal reasons for these patients to
      seek medical help. Nevertheless, the underlying mechanisms of chronic visceral
      pain have remained unclear, and much of what we know about visceral pain has been
      derived from studies of somatic nociception. Current treatment of chronic
      visceral pain has continued to be unsatisfactory, because of unclear
      pathophysiology. However, recent progress in pain research has identified the
      important role of spinal microglia in the development of somatic nociception. For
      visceral pain, several animal studies have demonstrated that spinal cord
      microglia is activated during the development of visceral hyperalgesia, which can
      be induced by neonatal colorectal irritation, psychological stress, and
      trinitrobenzene sulfonic acid-induced pancreatitis. This visceral hyperalgesia is
      also associated with elevated phosphorylation of p38 mitogen-activated protein
      kinase. Minocycline (a microglia inhibitor) reversed the hyperalgesia in rat
      models of chronic visceral pain, whereas fractalkine (FKN, a microglia activator)
      reproduced the visceral nociception in naive rats. These preliminary results
      support the pronociceptive role of spinal microglia in mediating visceral
      hyperalgesia. Consequently, spinal microglia may serve as a promising target for
      controlling the chronic visceral pain. 

PMID- 24090602
TI  - Structural study of interaction between brinzolamide and dorzolamide inhibition
      of human carbonic anhydrases.
AB  - Carbonic anhydrases (CAs, EC 4.2.1.1) are metalloenzymes that catalyze the
      reversible hydration of carbon dioxide and bicarbonate. Their pivotal role in
      metabolism, ubiquitous nature, and multiple isoforms (CA I-XIV) has made CAs an
      attractive drug target in clinical applications. The usefulness of CA inhibitors
      (CAIs) in the treatment of glaucoma and epilepsy are well documented. In addition
      several isoforms of CAs (namely, CA IX) also serve as biological markers for
      certain tumors, and therefore they have the potential for useful applications in
      the treatment of cancer. This is a structural study on the binding interactions
      of the widely used CA inhibitory drugs brinzolamide (marketed as Azopt(r)) and
      dorzolamide (marketed as Trusopt(r)) with CA II and a CA IX-mimic, which was
      created via site-directed mutagenesis of CA II cDNA such that the active site
      resembles that of CA IX. Also the inhibition of CA II and CA IX and molecular
      docking reveal brinzolamide to be a more potent inhibitor among the other
      catalytically active CA isoforms compared to dorzolamide. The structures show
      that the tail end of the sulfonamide inhibitor is critical in forming stabilizing
      interactions that influence tight binding; therefore, for future drug design it
      is the tail moiety that will ultimately determine isoform specificity. 

PMID- 24090604
TI  - Eradication of bluetongue disease in Germany by vaccination.
AB  - Bluetongue disease first broke out in Germany on 21 August 2006, almost
      simultaneously with the first outbreaks in Belgium and The Netherlands. More
      extensive tests showed that the serotype was serotype 8. Due to westerly winds
      the disease spread rapidly towards the East, with the result that in the year
      2008 large parts of Germany were affected. The traditional methods of animal
      disease control were not of much help in view of the transmission of the disease
      by insects; the speed of the spread of the disease could only be slowed down by
      movement restrictions, but could not be influenced in a decisive manner.
      Authorised vaccines were not (yet) available. A large-scale field study based on
      three prototypes in bovine animals and sheep revealed that they were both
      effective and safe. Consequently, the Federal Ministry of Food, Agriculture and
      Consumer Protection issued an exceptional permission to administer these non
      authorised vaccines. In May 2008, large-scale vaccination campaigns were launched
      (vaccination of all bovines, sheep and goats). As a consequence, the disease
      outbreak figures declined drastically. In 2009, the last blanket vaccinations
      were administered and from 2010 animal keepers were allowed to continue
      vaccinating their livestock on a voluntary basis. Intensive tests (serological,
      PCR) showed in the years 2010 and 2011 that BTV8 no longer circulated among the
      livestock population. Effective from 15.02.2012, Germany declared itself free
      from BTV8 in line with Article 8.3.3 of the OIE Animal Health Code. 

PMID- 24090603
TI  - Adverse events in cardiovascular-related training programs in people with spinal
      cord injury: a systematic review.
AB  - CONTEXT: There are anecdotal reports of adverse events (AEs) associated with
      exercise in people with spinal cord injury (SCI) and consequent concern by people
      with SCI and their providers about potential risks of exercise. Enumeration of
      specific events has never been performed and the extent of risk of exercise to
      people with SCI is not understood. OBJECTIVE: To systematically review published
      evidence to identify and enumerate reports of adverse events or AEs associated
      with training in persons with SCI. METHODS: Review was limited to peer-reviewed
      studies published in English from 1970 to 2011: (1) in adults with SCI, (2)
      evaluating training protocols consisting of repeated sessions over at least 4
      weeks to maintain or improve cardiovascular health, (3) including volitional
      exercise modalities and functional electrical stimulation (FES)-enhanced exercise
      modalities, and (4) including a specific statement about AEs. Trained reviewers
      initially identified a total of 145 studies. After further screening, 38 studies
      were included in the review. Quality of evidence was evaluated using established
      procedures. RESULTS: There were no serious AEs reported. There were no common AEs
      reported across most types of interventions, except for musculoskeletal AEs
      related to FES walking. There were few AEs in volitional exercise studies.
      CONCLUSION: There is no evidence to suggest that cardiovascular exercise done
      according to guidelines and established safety precautions is harmful. To improve
      the strength of these conclusions, future publications should include definition
      of AEs, information about pre-intervention screening, and statements of the
      nature and extent of AEs.

PMID- 24090605
TI  - Infections increase the risk of central venous catheter-related thrombosis in
      adult acute myeloid leukemia.
AB  - INTRODUCTION: Central venous catheters (CVC) related thrombosis (CRT) represents
      a well known complication in patients with acute myeloid leukemia (AML) receiving
      intensive chemotherapy but the efficacy of antithrombotic prophylaxis still
      remains controversial. PATIENTS AND METHODS: We analyzed 71 consecutive AML
      patients whose CVC was inserted before each chemotherapy cycle for an overall
      number of 106 CVC placements. In 47/106 insertions, a prophylaxis with 100
      IU/kg/day low molecular weight heparin (LMWH) was administered for 7 days after
      CVC insertion and additional 7 after CVC removal. This unconventional dose of
      LMWH, although higher than usual, appeared adequate for a short-course approach.
      LMWH was delivered regardless of the platelet (PLT) count once provided that it
      should have been maintained above 20 x 10(9)/L by transfusions. RESULTS: Of 106
      insertions, we observed 19 (18%) episodes of CRT, 58 (54%) of sepsis and 50 (47%)
      infections of CVC-exit site with no difference between LMWH and no-LMWH group.
      Occurrence of CRT was significantly associated with CVC-exit site infections
      (14/19, p=0.01) and sepsis (16/19, p=0.005) with no difference between LMWH and
      no-LMWH group. In multivariate analysis, both CVC-exit site infections and sepsis
      were confirmed to be independent risk factors for CRT development. CONCLUSION:
      Our retrospective study, although based on a small sample size, suggests that the
      occurrence of CVC-exit site infections and neutropenic sepsis following
      chemotherapy significantly increases the risk of CRT in AML, independently from
      the use of LMWH prophylaxis.

PMID- 24090606
TI  - Probucol and cilostazol exert a combinatorial anti-atherogenic effect in
      cholesterol-fed rabbits.
AB  - INTRODUCTION: Probucol (PB) and cilostazol (CZ) both exhibit anti-atherogenic
      effects. However, their combinatorial effects are unclear. This study was
      designed to investigate their combinatorial anti-atherogenic effect in
      cholesterol-fed rabbits. MATERIALS AND METHODS: Rabbits were fed a cholesterol
      diet with PB or CZ alone or both PB and CZ for 16 weeks. The plasma levels of
      total cholesterol, LDL-cholesterol, HDL-cholesterol, C-reactive protein,
      superoxide dismutase, malondialdehyde, and nitric oxide (NO) were measured. The
      aortic atherosclerotic lesions were grossly and microscopically evaluated.
      Additionally, in vitro experiments were conducted using human umbilical vein
      endothelial cells. RESULTS AND CONCLUSION: We found that the PB group and the
      PB+CZ group exhibited a reduction in the lesion areas (70% in the PB+CZ group,
      56% in the PB group) compared with the vehicle group. However, although PB alone
      and PB+CZ led to a reduction in the lesion size, the histological analysis
      revealed that only PB+CZ significantly decreased the macrophage accumulation and
      smooth muscle cell proliferation in the lesions compared with the vehicle group.
      The plasma levels of total cholesterol in the PB+CZ group were decreased compared
      with the vehicle group, Moreover, PB+CZ exerted obvious anti-oxidant and anti
      inflammatory effects. Interestingly, the PB+CZ treatment led to a marked increase
      in the levels of plasma NO. The in vitro experiments showed that the
      combinatorial treatment up-regulated the levels of NO and protein S-nitrosylation
      in endothelial cells treated with oxidized LDL. In summary, these results suggest
      that PB and CZ exert combinatorial anti-atherogenic effects.

PMID- 24090608
TI  - Off-label and unlicensed drug use in children.

PMID- 24090607
TI  - Quality of life after pulmonary embolism as assessed with SF-36 and PEmb-QoL.
AB  - INTRODUCTION: Although quality of life (QoL) is recognized as an important
      indicator of the course of a disease, it has rarely been addressed in studies
      evaluating the outcome of care for patients with pulmonary embolism (PE). This
      study primarily aimed to evaluate the QoL of patients with acute PE in comparison
      to population norms and to patients with other cardiopulmonary diseases, using a
      generic QoL questionnaire. Secondary, the impact of time period from diagnosis
      and clinical patient characteristics on QoL was assessed, using a disease
      specific questionnaire. METHODS: QoL was assessed in 109 consecutive out-patients
      with a history of objectively confirmed acute PE (mean age 60.4 +/- 15.0 years,
      56 females), using the generic Short Form-36 (SF-36) and the disease specific
      Pulmonary Embolism Quality of Life questionnaire (PEmb-QoL). The score of the SF
      36 were compared with scores of the general Dutch population and reference
      populations with chronic obstructive pulmonary disease (COPD), congestive heart
      failure (CHF), a history of acute myocardial infarction (AMI), derived from the
      literature. Scores on the SF-35 and PEmb-QoL were used to evaluate QoL in the
      short-term and long-term clinical course of patients with acute PE. In addition,
      we examined correlations between PEmb-QoL scores and clinical patient
      characteristics. RESULTS: Compared to scores of the general Dutch population,
      scores of PE patients were worse on several subscales of the SF-36 (social
      functioning, role emotional, general health (P<0.001), role physical and vitality
      (P<0.05)). Compared to patients with COPD and CHF, patients with PE scored higher
      (=better) on all subscales of the SF-36 (P <= 0.004) and had scores comparable
      with patients with AMI the previous year. Comparing intermediately assessed QoL
      with QoL assessed in long-term follow-up, PE patients scored worse on SF-36
      subscales: physical functioning, social functioning, vitality (P<0.05), and on
      the PEmb-QoL subscales: emotional complaints and limitations in ADL (P <= 0.03).
      Clinical characteristics did not correlate with QoL as measured by PEmb-QoL.
      CONCLUSION: Our study demonstrated an impaired QoL in patients after treatment of
      PE. The results of this study provided more knowledge about QoL in patients
      treated for PE.

PMID- 24090609
TI  - Impact of iron-based nanoparticles on microbial denitrification by Paracoccus sp.
      strain YF1.
AB  - This study investigates the effects of Fe and Fe/Ni nanoparticles on biological
      denitrification when using Paracoccus sp. strain YF1. Results show that adding Fe
      and Fe/Ni nanoparticles to the cells decreased their growth and denitrification
      rate. Compared to that of free cells (control 89.47%), a decrease (64.33%) in the
      presence of 1000 mg/L Fe/Ni nanoparticles was observed, while a small decline in
      the denitrification rate (76.36%) was obtained when the concentration of Fe
      nanoparticles was 1000 mg/L. These were further confirmed by adding Fe(2+),
      Fe(3+), Fe3O4, Fe(2+)/Ni(2+) and Fe(3+)/Ni(2+) individually to the free cell
      system. Furthermore, Fe and Fe/Ni nanoparticles influenced the nitrate removal
      and bacterial growth under different pH and temperature conditions. SEM, XRD and
      EDS demonstrated that iron oxides formed as a result of nanoparticles corrosion
      in biological medium. Finally the presence of nanoparticles around some bacteria
      was observed.

PMID- 24090610
TI  - Carboplatin-containing regimens as front-line treatment for advanced non-small
      cell lung cancer in two groups of elderly.
AB  - OBJECTIVES: We evaluated the impact of a carboplatin-based doublet in two groups
      of elderly patients with advanced non-small cell lung cancers (NSCLC). MATERIALS
      AND METHODS: A retrospective analysis of all consecutive elderly patients (?70
      year old) with advanced NSCLC who received a carboplatin-based doublet as front
      line therapy at our medical oncology unit was performed. RESULTS: In the study,
      57 consecutive elderly patients with advanced NSCLC were included. Carboplatin
      was combined with vinorelbine in 41 patients (71.9%) and with gemcitabine in 16
      patients (28.1%). Overall, a total of 227 cycles were administered to 57 patients
      - 142 cycles were administered to patients in group 1 and 85 cycles were given to
      patients in group 2 - median number of administered cycles per patient was 4
      (range 1-6). Of the patients, 35 (62%, group 1) were 'young-old' (70-74-year old)
      and 20 (38%, group 2) were 'old-old' (75-82-year old). Toxicity was mild in both
      subgroups (grade 3-4 neutropenia in 17.1% of group 1 and in 9.1% of group 2). At
      the univariate analysis, the median overall survival (OS) was 10.07 months (P =
      0.789, 95% CI: 8.49-11.64), 10.1 months in group 1 and 9.8 months in group 2.
      CONCLUSIONS: This evaluation shows the safety and efficacy of a carboplatin-based
      doublet given as first-line chemotherapy in elderly advanced NSCLC patients. The
      combination with vinorelbine or gemcitabine is associated with a very good
      toxicity profile that does not seem to have a detrimental effect on efficacy.

PMID- 24090611
TI  - Differential effects of yolk testosterone and androstenedione in embryo
      development and nestling growth in the spotless starling (Sturnus unicolor).
AB  - Yolk androgens in avian eggs play a significant role in embryo and nestling
      development. However, few studies have examined the differential effect of two of
      the main yolk androgens, testosterone (T) and androstenedione (A4). Here, we
      injected eggs of spotless starlings with physiological levels of either T, A4,
      the combination T+A4 or vehicle substance (control), to examine the differential
      ability of these steroids to influence nestling development. We found that the
      duration of the embryonic period was increased by T, and less so by A4, but not
      by the combination T+A4. Body condition was reduced in all experimental
      treatments where A4 was present, particularly so in the combination T+A4. Tarsus
      length was increased in males by A4, and in a lower degree by T, whereas the
      combination T+A4 inhibited growth. However, these differences in tarsus length
      between groups disappeared at the end of the nestling period. Cell-mediated
      immune responsiveness was marginally affected by the interaction between
      treatment and sex. These patterns suggest that in this species, T has a stronger
      influence during embryo development than A4, whereas during nestling development
      the capacities of both androgens to influence growth are similar. The combination
      T+A4 showed non-additive effects, suggesting either some kind of inhibition
      between the two androgens, or else an excessive effect due to a bell-shaped
      pattern of response. Our results suggest a complex picture of sex and age
      dependent effects of T and A4, and underline the necessity of further research in
      the metabolism and action of egg androgens. 

PMID- 24090612
TI  - Possible roles of photoperiod and melatonin in reproductive activity via changes
      in dopaminergic activity in the brain of a tropical damselfish, Chrysiptera
      cyanea.
AB  - The perception of periodical change in photoperiodic conditions by photosensory
      organs is the first step to initiating reproductive activity in fish. To date, it
      is not known how photoperiodic cues are endogenously transduced to the endocrine
      network of the brain-pituitary-gonad axis after the perception of photoperiodic
      stimuli. Because dopamine (DA) inhibits gonadotropin release from the pituitary
      in certain teleosts, it is likely that it is a key mediator of photoperiodic
      stimulation. We examined the relationship between photoperiodicity and
      dopaminergic activity in the brain of the sapphire devil Chrysiptera cyanea,
      which is a reef-associated damselfish and uses long-day conditions for triggering
      gonadal development. DA and 3,4-dihydroxyphenylacetic acid (DOPAC; DA metabolite)
      were measured electrochemically with a high-performance liquid chromatography
      (HPLC) system, and then DOPAC/DA (metabolic rate of DA activity) was determined.
      Daily fluctuations in DA, DOPAC, and DOPAC/DA were observed under LD 12:12. Light
      dark cycles, but not constant conditions, influenced DA and DOPAC contents as
      well as DOPAC/DA in the brain; DOPAC content and DOPAC/DA increased under LD
      14:10, while DA increased under LD 10:14. When fish were reared in melatonin
      containing water, DOPAC and DOPAC/DA, but not DA, decreased within 6h after
      treatment. Culturing the isolated brain with melatonin stimulated DA release into
      the medium. Active vitellogenesis in females during the reproductive season was
      suppressed by melatonin treatment. These results suggest that day length alters
      DA metabolism in the brain of the sapphire devil through fluctuations in
      melatonin caused by external light stimuli, and that inhibitory effects on
      gonadal development are partially controlled by interactions within the melatonin
      DA system. 

PMID- 24090613
TI  - Sources of variation in HPG axis reactivity and individually consistent elevation
      of sex steroids in a female songbird.
AB  - Understanding sources of individual differences in steroid hormone production has
      important implications for the evolution of reproductive and social behaviors. In
      females in particular, little is known about the mechanistic sources of these
      individual differences, despite established linkages between sex steroids and a
      variety of fitness-related traits. Using captive female dark-eyed juncos (Junco
      hyemalis) from two subspecies, we asked how variation in different components of
      the hypothalamo-pituitary-gonadal (HPG) axis related to variation in testosterone
      production among females, and we compared females to males in multiple components
      of the HPG axis. We demonstrated consistent individual differences in
      testosterone elevation in response to challenges with luteinizing hormone (LH)
      and gonadotropin-releasing hormone (GnRH). These hormone challenges led to more
      LH production but less testosterone production in females than males, and the
      sexes differed in some but not all measures of sensitivity to hormones along the
      HPG axis. Similar to findings in males, variation in testosterone production
      among females was not related to variation in LH production, gonadal LH-receptor
      mRNA abundance, or hypothalamic abundance of androgen receptor mRNA or aromatase
      mRNA. Rather, the primary source of individual variation in circulating steroids
      appears to the gonad, a conclusion further supported by positive correlations
      between testosterone and estradiol production. Unlike males, females did not
      differ by subspecies in any of the endocrine parameters that we assessed,
      suggesting some degree of independent evolution between the two sexes. Our
      results highlight the sources of physiological variation that may underlie the
      evolution of hormone-mediated phenotypes in females. 

PMID- 24090615
TI  - Nursing education in the European higher education area - variations in
      implementation.
AB  - BACKGROUND: The European Higher Education Area (EHEA) aims to ensure comparable,
      compatible and coherent systems of higher education. OBJECTIVES: The purpose of
      this study was to statistically analyze nursing education in Europe. Analysis was
      based on the quantitative determinants essential in describing the implementation
      of nursing education. First, nursing education in the 45 member countries of the
      EHEA was analyzed. Second, nursing education in the 29 original member countries
      was analyzed in more detail. Both analyses focused on the similarities and
      differences between nations. METHODS: A systematic literary review design was
      used. Data collection was conducted based on key quantitative determinants used
      to describe the implementation of nursing education. These determinants were
      based on the European Union standards and recommendations by the EHEA. Data were
      collected from three sources: research articles, internet databases and emails.
      The literature was analyzed using deductive content analysis. The data were
      quantified, studied and compared and the results were described based on
      frequencies and percentages and presented in tables. RESULTS: More similarities
      than differences in nursing education were noted between the different EHEA
      member countries. A full academic pathway of studying for a bachelor's degree, a
      master's degree and a doctorate in nursing was offered in 60% of the countries.
      Nevertheless, there are still countries offering education only on the diploma
      level, demonstrating that the differences between countries are at points rather
      significant. CONCLUSIONS: Based on the analyses, it is evident that there are
      still rather significant differences between countries and that support for
      aligning national practices and mobility is needed. A common ground in
      terminology and evidence-based recommendations published in English would be
      beneficial for countries currently developing nursing education programs. We also
      suggest creating an online database containing information on nursing education
      for all 45 member countries to support the mobility of nursing students, nurses
      and researchers.

PMID- 24090616
TI  - Competence and competency-based nursing education: finding our way through the
      issues.
AB  - The language of competence is widely utilized in both the regulation of nursing
      practice and curricular design in nursing education. The notion of competence
      defines what it means to be a professional, although it is not the only way of
      describing nursing practice. Unfortunately, there is much confusion about the
      concepts of competence, competency, and competency-based education. As well, the
      notion of competence, despite its global popularity, has flaws. In this paper we
      will disentangle these terms and critique the use of competence frameworks in
      nursing education. 

PMID- 24090617
TI  - Why here and why stay? Students' voices on the retention strategies of a widening
      participation university.
AB  - BACKGROUND: Whilst concern about nursing student retention remains a key priority
      of governments and educators, much research is focussed on determining the causes
      and experiences of withdrawal. Further work is required to understand the
      perspectives of those students who successfully negotiate their programme of
      study. OBJECTIVES: The study aimed to explore student motivations, experiences
      and support requirements during their first year to determine the efficacy of
      institutional retention initiatives. DESIGN: Qualitative data collection through
      focus groups at two intervals in the year. SETTINGS: University class rooms.
      PARTICIPANTS: 46 first year nursing and midwifery students. METHODS: After
      collection, the data was subjected to grounded theory-driven coding and thematic
      analysis. Coding was undertaken independently before mutual verification and
      theming took place. RESULTS: Students utilise a range of support mechanisms
      before and during their studies in order to maintain their motivation and to
      juggle the many demands on their time. These include university staff, fellow
      students, friends and family and those they currently know within the profession.
      CONCLUSIONS: Expectations play a significant role in student satisfaction,
      suggesting that institutions should ensure prospective students have a realistic
      understanding of what a nursing/midwifery programme and career will entail.
      Nurturing a sense of belonging to both the university and profession appears
      beneficial in promoting retention.

PMID- 24090614
TI  - Multiple structurally distinct ERalpha mRNA variants in zebrafish are
      differentially expressed by tissue type, stage of development and estrogen
      exposure.
AB  - It is well established that estrogen-like environmental chemicals interact with
      the ligand-binding site of estrogen receptors (ERs) to disrupt transcriptional
      control of estrogen responsive targets. Here we investigate the possibility that
      estrogens also impact splicing decisions on estrogen responsive genes, such as
      that encoding ERalpha itself. Targeted PCR cloning was applied to identify six
      ERalpha mRNA variants in zebrafish. Sequencing revealed alternate use of
      transcription and translation start sites, multiple exon deletions, intron
      retention and alternate polyadenylation. As determined by quantitative (q)PCR, N
      terminal mRNA variants predicting long (ERalphaA(L)) and short (ERalpha(S))
      isoforms were differentially expressed by tissue-type, sex, stage of development
      and estrogen exposure. Whereas ERalpha(L) mRNA was diffusely distributed in
      liver, brain, heart, eye, and gonads, ERalpha(S) mRNA was preferentially
      expressed in liver (female>male) and ovary. Neither ERalpha(L) nor ERalpha(S)
      transcripts varied significantly during development, but 17beta-estradiol
      selectively increased accumulation of ERalpha(S) mRNA (~170-fold by 120 hpf), an
      effect mimicked by bisphenol-A and diethylstilbestrol. Significantly, a C
      truncated variant (ERalpha(S)-Cx) lacking most of the ligand binding and AF-2
      domains was transcribed exclusively from the short isoform promoter and was
      similar to ERalpha(S) in its tissue-, stage- and estrogen inducible expression.
      These results support the idea that promoter choice and alternative splicing of
      the esr1 gene of zebrafish are part of the autoregulatory mechanism by which
      estrogen modulates subsequent ERalpha expression, and further suggest that
      environmental estrogens could exert some of their toxic effects by altering the
      relative abundance of structurally and functionally distinct ERalpha isoforms.

PMID- 24090618
TI  - How do university education and clinical experience influence pre-registration
      nursing students' infection control practice? A descriptive, cross sectional
      survey.
AB  - AIMS: This study aims to explore nursing students' knowledge of infection control
      and investigate how university education and clinical experience influence their
      infection control practice. BACKGROUND: In order to prevent and control
      healthcare associated infections all healthcare staff must be knowledgeable about
      infection control. However, knowledge and practice of infection control are often
      sub-optimal. Education has had variable results in improving the infection
      control knowledge of healthcare professionals yet, there have been few studies
      examining this issue in relation to pre-registration nursing students in the
      United Kingdom. METHODS: This descriptive cross-sectional survey employed a
      questionnaire composed of predominantly closed questions for data collection. A
      non-probability, purposive sample of 354/444 (79.7%) nursing students from one
      university participated in the study. FINDINGS: Knowledge was generally adequate
      in questions related to pathogen transmission, hand hygiene principles, glove
      use, immediate action following sharps' injuries, and risk reduction in relation
      to sharps and waste management. Topics that received less positive results
      related to the chain of infection, the use of alcohol gel and Clostridium
      difficile and the definition of inoculation injury. University education was the
      main influence on knowledge and practice (340/353, 96.3%), but mentors (322/354,
      91.2%), nurses (316/353, 89.3%), doctors (175/353, 49.4%) and other members of
      the multi-disciplinary team (213/352, 60.2%) were also deemed influential.
      Workload, time, and availability of facilities and equipment also contributed to
      the adoption of infection control precautions. The findings illustrated the
      importance of both theoretical and practical knowledge, supported by competent
      role models. CONCLUSION: The study identified the complexities of knowledge
      acquisition and application in a practice based discipline. The support of a
      competent role model to assist in applying theory to practice is vital. The study
      has identified that there are many variables that affect IPC practice, both
      positively and negatively.

PMID- 24090619
TI  - Characteristics and drinking patterns of veterans with alcohol dependence with
      and without post-traumatic stress disorder.
AB  - Alcohol use disorders and post-traumatic stress disorder (PTSD) are highly
      prevalent and commonly co-occur, notably in veterans. We explored differences in
      the pre-treatment characteristics of veterans with alcohol dependence (AD) alone
      compared to those with co-occurring AD and PTSD. Veterans were recruited to
      participate in two different treatment studies and baseline characteristics were
      compared. Those with co-occurring illnesses demonstrated significantly higher pre
      treatment pathology across all psychopathological domains. While those with AD
      alone averaged more days of drinking and had more heavy drinking days, those with
      co-occurring illnesses reported more drinking-related symptoms. The presence of a
      major depressive episode had no effect on drinking. Within the PTSD group, combat
      exposure was associated with increased drinking independent of the severity of
      PTSD symptoms. This study underscores the importance of screening for comorbidity
      in clinical treatment settings, and for collecting detailed drinking histories
      and assessing psychiatric symptoms across all domains of psychopathology. 

PMID- 24090620
TI  - Effects of caffeinated vs. non-caffeinated alcoholic beverage on next-day
      hangover incidence and severity, perceived sleep quality, and alertness.
AB  - AIMS: Beliefs about the effects of mixing caffeine and alcohol on hangover or
      sleep may play a role in motivation to consume these mixtures; therefore,
      information is needed about actual effects. We investigated whether intoxication
      with caffeinated vs. non-caffeinated beer differentially affected perceived sleep
      quality, sleepiness, and hangover incidence and severity the next morning.
      METHODS: University students (89%) and recent graduate drinkers were randomized
      to receive: (1) beer with the equivalent of 69mg caffeine/12oz glass of regular
      beer (n=28) or (2) beer without caffeine (n=36), in sufficient quantity to attain
      a BrAC of 0.12g%. After an 8-h supervised sleep period, participants completed
      measures of hangover, sleep quality, sleep latency and time asleep, and
      sleepiness. RESULTS: While caffeinated beer improved perceived sleep quality,
      effect sizes were greater for morning alertness than for quality while sleeping,
      with no effect on sleep latency or total sleep time. No effects were seen on
      hangover incidence or severity. CONCLUSIONS: Mixing caffeine and alcohol does not
      significantly impair amount of sleep or sleep latency, hangover, or sleepiness
      the morning after drinking to intoxication in this population.

PMID- 24090621
TI  - Problem solving styles among people who use alcohol and other drugs in South
      Africa.
AB  - The present study examines the relationship between problem-solving styles, socio
      demographic variables and risk of alcohol and other drug (AOD)-related problems
      among a South African population. The Social Problem-Solving Inventory-Revised,
      Center for Epidemiologic Studies Depression Scale (CES-D) and the Alcohol,
      Smoking and Substance Involvement Screening Test (ASSIST) were administered to a
      convenience sample of 1000 respondents. According to the ASSIST, 32% and 49% of
      respondents met criteria for moderate to high risk of alcohol use and illicit
      drug use respectively. After adjusting for the effects of other variables in the
      model, respondents who were of "Coloured" ancestry (PR=1.20, 95% CI 1.0-1.4),
      male (PR=1.19, 95% CI 1.04-1.37), older (PR=1.01, 95% CI 1.00-1.02), who adopted
      an avoidance style of coping with problems (PR=1.03, 95% CI 1.01-1.05) and who
      met criteria for depression (PR=1.42, 95% CI 1.12-1.79) were more likely to be
      classified as having risky AOD use. This suggests that interventions to improve
      problem solving and provide people with cognitive strategies to cope better with
      their problems may hold promise for reducing risky AOD use. 

PMID- 24090622
TI  - Veterans' attitudes toward work and disability compensation: associations with
      substance abuse.
AB  - INTRODUCTION: Veterans deemed disabled for conditions resulting from, or
      aggravated by, their service in the military are eligible for service-connected
      disability payments. Despite many positive effects of disability payments, one
      concern is that Veterans with psychiatric conditions who receive disability
      payments are less likely to be employed compared to those who are denied
      benefits. Little is known about the attitudes of substance using Veterans, for
      whom work is a particularly important part of recovery, toward work and
      disability compensation. METHODS: This study compared the responses of Veterans
      with (n=33) and without substance use problems (n=51) to questions about work's
      significance and its relationship to disability payments. T- and chi-square tests
      were conducted to determine if Veterans with substance use problems differed from
      the others on work-related attitudes and perceptions of the relation between work
      and Veterans' benefits. RESULTS: Veterans endorsed high levels of agreement with
      statements that working would lead to loss of benefits. Veterans with substance
      use agreed more strongly that they would rather turn down a job offer than lose
      financial benefits. CONCLUSIONS: The greater preference for disability payments
      among substance-using Veterans may reflect a realistic concern that they are
      particularly likely to have difficulty maintaining employment. The widespread
      concern among Veterans that work will lead to loss of VA disability payments is
      striking given the ambiguity about how likely loss of benefits actually is, and
      should be addressed during the service-connection application process.

PMID- 24090623
TI  - DSM IV axis II traits can influence compliance to treatment with oral naltrexone:
      a preliminary study on 30 opiate dependent patients.
AB  - For many decades, health specialists have successfully used their clinical
      ingenuity to increase the efficiency of opiate detoxification protocols. However,
      even if drop-out rate has decreased significantly in today's protocols, relapse
      after opiate detoxification remains a major problem. Therefore, naltrexone
      hydrochloride, an opiate antagonist, has been considered by many as a potential
      tool to support abstinence in what has been called "antagonist-assisted
      abstinence" (AAA). Nevertheless, while naltrexone implants are becoming more
      accessible, a large majority of centers still use oral naltrexone and adherence
      to treatment remains a major obstacle to AAA's efficiency. As the personality
      profile could give an insight into compliance, we investigated the relationship
      between personality profiles and naltrexone adherence in a cohort of 30 patients.
      The results indicate that the Axis II profile influences the likely pattern of
      oral naltrexone compliance. As clinicians need to identify opiate dependent
      patients who are most likely to benefit from oral naltrexone treatment, it
      therefore carries important implications and could lead to a better adjustment of
      therapeutic strategies for opiate dependent patients. 

PMID- 24090624
TI  - ADHD, stimulant treatment in childhood and subsequent substance abuse in
      adulthood - a naturalistic long-term follow-up study.
AB  - The purpose of the study was to estimate the risk of substance use disorder (SUD)
      and alcohol abuse in adulthood among children and adolescents with attention
      deficit hyperactivity disorder (ADHD) compared to the background population.
      Furthermore, to examine whether the age at initiation and duration of stimulant
      treatment in childhood predicts SUD and alcohol abuse in adulthood. 208 youths
      with ADHD (183 boys; 25 girls) were followed prospectively. Diagnoses of SUD and
      alcohol abuse were obtained from The Danish Psychiatric Central Register. The
      relative risk (RR) of SUD and alcohol abuse for cases with ADHD, compared to the
      background population was 7.7 (4.3-13.9) and 5.2 (2.9-9.4), respectively. Female
      gender, conduct disorder in childhood and older age at initiation of stimulant
      treatment increased the risk of later SUD and alcohol abuse. Our results warrant
      increased focus on the possibly increased risk of substance abuse in females with
      ADHD compared to males with ADHD. 

PMID- 24090625
TI  - Alcohol misuse and psychological resilience among U.S. Iraq and Afghanistan era
      veterans.
AB  - OBJECTIVE: The present study sought to investigate the longitudinal effects of
      psychological resilience against alcohol misuse adjusting for socio-demographic
      factors, trauma-related variables, and self-reported history of alcohol abuse.
      METHODOLOGY: Data were from the National Post-Deployment Adjustment Study (NPDAS)
      participants who completed both a baseline and one-year follow-up survey
      (N=1090). Survey questionnaires measured combat exposure, probable posttraumatic
      stress disorder (PTSD), psychological resilience, and alcohol misuse, all of
      which were measured at two discrete time periods (baseline and one-year follow
      up). Baseline resilience and change in resilience (increased or decreased) were
      utilized as independent variables in separate models evaluating alcohol misuse at
      the one-year follow-up. RESULTS: Multiple linear regression analyses controlled
      for age, gender, level of educational attainment, combat exposure, PTSD symptom
      severity, and self-reported alcohol abuse. Accounting for these covariates,
      findings revealed that lower baseline resilience, younger age, male gender, and
      self-reported alcohol abuse were related to alcohol misuse at the one-year follow
      up. A separate regression analysis, adjusting for the same covariates, revealed a
      relationship between change in resilience (from baseline to the one-year follow
      up) and alcohol misuse at the one-year follow-up. The regression model evaluating
      these variables in a subset of the sample in which all the participants had been
      deployed to Iraq and/or Afghanistan was consistent with findings involving the
      overall era sample. Finally, logistic regression analyses of the one-year follow
      up data yielded similar results to the baseline and resilience change models.
      CONCLUSIONS: These findings suggest that increased psychological resilience is
      inversely related to alcohol misuse and is protective against alcohol misuse over
      time. Additionally, it supports the conceptualization of resilience as a process
      which evolves over time. Moreover, our results underscore the importance of
      assessing resilience as part of alcohol use screening for preventing alcohol
      misuse in Iraq and Afghanistan era military veterans.

PMID- 24090627
TI  - Retention in methadone maintenance treatment in mainland China, 2004-2012: a
      literature review.
AB  - BACKGROUND: Methadone maintenance treatment (MMT) was implemented in mainland
      China since 2004. Numerous individual studies have investigated MMT retention but
      the overview still remains unclear. The aim of the study was to review MMT
      retention rates and predicting factors in mainland China during 2004-2012.
      METHODS: Chinese and English databases of literature were searched for studies
      reporting on retention rates and predicting factors in non-transfer MMT patients
      of fixed-site clinics in mainland China (2004-2012). Qualitative methods were
      used to synthesize the results. RESULTS: Nineteen studies were eligible for
      review, with sample size ranging from 29 to 3758. Retention rates varied between
      30.0% at 6 months in Shanghai and 70.3% at 12 months in Xi'an. Predicting factors
      were non-treatment including sociodemographics (n=14), support system and social
      function (n=9), economic status (n=2) and psychological status (n=1), and
      treatment-related including drug use (n=15), methadone use (n=12), MMT clinics
      (n=9), MMT participation (n=7), awareness on MMT (n=5) and HIV serostatus (n=3).
      Methadone dose (n=12) and age (n=7) were the first two important specific
      factors. CONCLUSIONS: In mainland China, MMT retention rates are heterogeneous
      and relatively lower, and predicting factors mainly focus on objective aspects.
      Future work should further explore subjective predicting factors regarding MMT
      retention.

PMID- 24090626
TI  - Young adults who smoke cigarettes and marijuana: analysis of thoughts and
      behaviors.
AB  - INTRODUCTION: Smoking both cigarettes and marijuana is increasingly common among
      young adults, yet little is known about use patterns, motivations, or thoughts
      about abstinence. In a U.S. sample, this study explored young adults' severity of
      cigarette and marijuana co-use, quit attempts, and thoughts about use. METHODS:
      Young adults age 18-to-25 who had smoked at least one cigarette in the past 30
      days completed an anonymous online survey. RESULTS: Of 1987 completed surveys,
      972 participants reported both past-month cigarette and marijuana use (68% male,
      71% Caucasian, mean age 20.4 years [SD=2.0]). Frequency of use, temptations to
      use, measures of dependence, decisional balance, and past-year quit attempts were
      associated across the two substances (all p<.05), but not motivation to quit.
      Relative to marijuana, participants reported greater desire and a later stage of
      change for quitting cigarettes and were more likely to endorse a cigarette
      abstinence goal, yet they had lower expectancy of success with quitting
      cigarettes and with staying quit (all p<.001). CONCLUSIONS: Cigarette and
      marijuana use, temptations to use, and pros/cons of using were related in this
      young adult sample. Differences in motivation and thoughts about abstinence,
      however, suggest that young adults may be more receptive to interventions for
      tobacco than marijuana use. Use patterns and cognitions for both substances
      should be considered in prevention and intervention efforts.

PMID- 24090628
TI  - The association between tramadol hydrochloride misuse and other substances use in
      an adolescent population: Phase I of a prospective survey.
AB  - BACKGROUND: Tramadol hydrochloride is a common prescription pain reliever that is
      structurally similar to morphine and codeine with its analgesic effects
      identified as a mu-receptor agonist. Due to its opioid-like stimulant effects,
      the potential for tramadol misuse is a public health concern. As such, the aim of
      this investigation is to estimate the prevalence of tramadol misuse in a sample
      of Iranian adolescents and to assess the relationship between tramadol misuse and
      other substance use. METHODS: This is the first phase of a prospective survey
      examining the prevalence of adolescent smoking status, substances use and related
      factors in Ilam city, Iran. Grade 10 male and female students (n=2000) were
      recruited using multistage sampling. Self-administered multiple-choice
      questionnaires were conducted with data analysed using cross tabulations and
      logistic regression models. RESULTS: The prevalence of lifetime tramadol misuse
      was 4.8% (7.6% males; 1.8% females). Adjusted odds ratios and confidence
      intervals for lifetime tramadol misusers reporting substance use during the past
      month were 2.2 (1.1-4.4) for alcohol, 5.0 (1.5-21.9) for cannabis, 8.9 (2.7-29.4)
      for ecstasy, 0.5 (0.03-7.0) for methamphetamine and 2.3 (0.7-7.4) for opium.
      CONCLUSION: Tramadol could be a related factor or co-factor for adolescent
      alcohol, cannabis and ecstasy use. We recommend future longitudinal studies to
      investigate the possible role of tramadol as a gateway drug in the development of
      substance abuse.

PMID- 24090630
TI  - EBSD study of angular deviations from the Goss component in grain-oriented
      electrical steels.
AB  - The magnetic properties of grain-oriented (GO) electrical steels strongly depend
      on the distribution of the alpha and beta angles, i.e., the deviations of the
      easy magnetisation <100> from the rolling direction (RD) in the rolling plane and
      out of the rolling plane, respectively. However, most Electron Backscatter
      Diffraction (EBSD) studies consider the standard Goss deviation angle, which
      includes the rotation of the (110) plane about the RD. Therefore, in the present
      work, a new procedure is demonstrated for deriving the alpha and beta angles from
      EBSD mappings to obtain a quantitative texture characterisation in line with the
      magnetic properties. This procedure is later applied to 37 GO steels after
      secondary recrystallisation that exhibit a wide range of permeability levels. The
      relation between the texture and the polarisation at 800A/m (J800) that is
      measured in the present study by EBSD is compared to the one that has been
      determined in previous papers with optical goniometers and X-ray diffraction
      techniques, and this relation is subsequently used to define a relevant parameter
      to describe the orientation quality of the grains. The results indicate that the
      average angle of the alpha and beta deviations is a relevant deviation parameter
      for the characterisation of grain orientations. Finally, it is demonstrated that
      the combination of the quantitative correlation between polarisation and texture
      with the orientation imaging of EBSD offers the possibilities of both studying
      the crystallographic environment of highly oriented grains in the primary
      recrystallised matrix for the production of high-permeability steels and
      evaluating the spatial distribution of the angular deviations in GO steels after
      secondary recrystallisation.

PMID- 24090631
TI  - Evaluation of orchiopexy practice patterns in patients with cryptorchidism: a
      single-centre study.
AB  - OBJECTIVE: A retrospective study was conducted to determine the age at which
      orchiopexy was performed, and the laterality and anatomic location of undescended
      testes (UDTs) or non-palpable testes (NPTs). All documented orchiopexies
      performed in a large referral centre of Qom province, Qom, Iran during a 5 year
      period were evaluated. MATERIALS AND METHODS: A total of 324 patients admitted
      for surgical correction of cryptorchidism from 2005 to 2009 were eligible for
      inclusion in our study. The patients were divided into two groups: group A
      paediatric orchiopexy, and group B adult orchiopexy. RESULTS: There were 252
      paediatric patients (78%), with a mean age of 4.44 years, and 72 adult patients
      (22%). Forty-three patients (17%) were under 2 years of age and 59 patients
      (23.5%) were between 2 and 3 years. Right-side involvement was seen in 126
      patients (50%), left-side in 91 patients (36%), and bilateral involvement in 35
      patients (14%). Unilateral cryptorchidism was seen in 217 patients (85%).
      Regarding the anatomical location of the testes in unilateral cryptorchidism,
      superficial inguinal testis was seen in 117 patients (54%). CONCLUSION: The
      higher age of orchiopexies determined from this study compared with the
      recommended age for surgery, indicates that active interventions are necessary
      with public health education programs for patients, parents, midwives and general
      practitioners.

PMID- 24090629
TI  - Prepubertal exposure to arsenic(III) suppresses circulating insulin-like growth
      factor-1 (IGF-1) delaying sexual maturation in female rats.
AB  - Arsenic (As) is a prevalent environmental toxin readily accessible for human
      consumption and has been identified as an endocrine disruptor. However, it is not
      known what impact As has on female sexual maturation. Therefore, in the present
      study, we investigated the effects of prepubertal exposure on mammary gland
      development and pubertal onset in female rats. Results showed that prepubertal
      exposure to 10 mg/kg of arsenite (As(III)) delayed vaginal opening (VO) and
      prepubertal mammary gland maturation. We determined that As accumulates in the
      liver, disrupts hepatocyte function and suppresses serum levels of the puberty
      related hormone insulin-like growth factor 1 (IGF-1) in prepubertal animals.
      Overall, this is the first study to show that prepubertal exposure to As(III)
      acts peripherally to suppress circulating levels of IGF-1 resulting in delayed
      sexual maturation. Furthermore, this study identifies a critical window of
      increased susceptibility to As(III) that may have a lasting impact on female
      reproductive function.

PMID- 24090633
TI  - Erythropoiesis-stimulating agents in chronic kidney disease: what have we learned
      in 25 years?
AB  - Since the pioneering studies by Eschbach et al in 1987, erythropoiesis
      stimulating agents (ESAs) have become the mainstay of anemia therapy in chronic
      kidney disease (CKD) patients. The introduction of ESAs 25 years ago markedly
      improved the lives of many patients with CKD, who until then had severe, often
      transfusion-dependent anemia. However, randomized controlled trials demonstrate
      an increased risk for cardiovascular events such as stroke, thrombosis, and death
      at nearly normal hemoglobin concentrations and higher ESA doses in CKD. By
      contrast, kidney transplant recipients may represent a unique population of CKD
      patients who may benefit from ESA therapy. This review discusses potential
      mechanisms involving the erythropoietic and nonerythropoietic effects of ESA
      treatment and ESA resistance. Further research aimed at elucidating the causal
      pathways is strongly recommended. Given current knowledge, however, clinical
      practice should avoid disproportionately high dosages of ESAs to achieve
      recommended hemoglobin targets, particularly in those with significant
      cardiovascular morbidity or ESA resistance. The key to CKD anemia management will
      be individualization of the potential benefits of reducing blood transfusions and
      anemia-related symptoms against the risks of harm.

PMID- 24090634
TI  - Risk of nonpsychotic mental disorders development in antiviral-treated mentally
      healthy chronic hepatitis C patients: A population-based study.
AB  - BACKGROUND/PURPOSE: Interferon (IFN) is able to induce significant psychiatric
      side effects in chronic hepatitis C (CHC) patients, whereas the risk of
      nonpsychotic mental disorder (NPMD) development in antiviral-treated mentally
      healthy CHC patients remains obscure. We used a population-based study to assess
      the risk of NPMD development in patients who had undergone antiviral treatment
      compared with untreated chronic hepatitis C virus (HCV)-infected and nonalcoholic
      fatty liver disease (NAFLD) patients. METHODS: Data were retrieved from Taiwan's
      National Health Insurance Research Database cohort consisting of 1 million
      individuals for a longitudinal analysis. A total of 313 mentally healthy CHC
      patients who received IFN-based antiviral therapy were recruited and compared
      with those without antiviral therapy and NAFLD patients. The Chi-square test was
      used to obtain the hazard ratio and 95% confidence interval. RESULTS: Among the
      313 CHC patients receiving pegylated interferon/ribavirin therapy, 62 patients
      (19.8%) were associated with NPMD. In the comparison cohort, composed of 313 age-
      and sex-matched CHC patients not receiving antiviral therapy, 70 patients (22.4%)
      were associated with NPMD. The Chi-square analysis revealed that antiviral
      therapy was not significantly associated with NPMD. The diagnosis of HCV-infected
      hepatitis was independently associated with NPMD when compared with NAFLD. The
      hazard ratio was 1.67 (95% confidence interval, 1.11-2.52; p = 0.018).
      Furthermore, generalized anxiety disorder was specifically higher in HCV-infected
      patients than those with NAFLD. CONCLUSION: Patients with HCV infection are at
      high risk of developing NPMD with or without IFN-based therapy.

PMID- 24090635
TI  - Endosonography for suspected obstructive jaundice with no definite pathology on
      ultrasonography.
AB  - BACKGROUND/PURPOSE: Ultrasonography (US) cannot demonstrate all the etiologies of
      biliary tract dilatation in patients with jaundice. Thus, we evaluated the
      etiologic yield of endosonography (EUS) for suspected obstructive jaundice when
      no definite pathology was found on US. Additionally, we sought to identify the
      predictors of the most common etiologies. METHODS: We performed a retrospective
      review of 123 consecutive patients who had undergone EUS for suspected
      obstructive jaundice when no definite pathology was identified on US. RESULTS:
      The most common diagnoses included no pathological obstruction (n = 43),
      pancreatobiliary malignancy (n = 41), and choledocholithiasis (n = 28).
      Pancreatobiliary malignancy was associated with common bile duct (CBD)
      dilatation, and fever and elevated alanine aminotransferase were predictors of
      choledocholithiasis (p < 0.05). The accuracy of EUS was 95.9% (118/123) for
      overall cause of suspected obstructive jaundice, 100% (40/40) for no pathological
      finding, 100% (23/23) for ampullary cancer, 100% (13/13) for pancreatic cancer,
      75% (3/4) for CBD cancer, and 92.9% (26/28) for choledocholithiasis,
      respectively. Besides the two patients with focal chronic pancreatitis
      misdiagnosed as with pancreatic cancer, EUS missed the lesions in one CBD cancer
      patient and two patients with choledocholithiasis. The overall accuracy of EUS in
      ascertaining pancreatobiliary malignancy and choledocholithiasis was comparable
      (97.6%, 40/41 vs. 92.9%, 26/28; p > 0.05). CONCLUSION: Marked CBD dilatation
      (>=12 mm) should remind us of the high risk of malignancy, and the presence of
      CBD dilatation and fever is suggestive of choledocholithiasis. Negative EUS
      findings cannot assure any pathological obstruction in patients with clinically
      suspected obstructive jaundice.

PMID- 24090636
TI  - Effect of mannitol on cerebrovascular pressure reactivity in patients with
      intracranial hypertension.
AB  - BACKGROUND/PURPOSE: Mannitol is commonly used in patients with increased
      intracranial pressure (ICP), but its effect on cerebrovascular pressure
      reactivity (CVPR) is uncertain. We analyzed the changes of pressure reactivity
      index (PRx) during the course of mannitol treatment. METHODS: Twenty-one patients
      who received mannitol treatment for increased ICP were recruited prospectively.
      Continuous waveforms of arterial blood pressure (ABP) and ICP were collected
      simultaneously for 60 minutes (10 minutes at baseline and 50 minutes since
      mannitol administration) during 37 events of mannitol treatment. The correlation
      coefficients between the mean ABP and ICP were averaged every 10 minutes and
      labeled as the PRx. The linear correlation of six time points of PRx in each
      event was calculated to represent the trend of CVPR changes. The negative slope
      of correlation was defined as improvement in CVPR under mannitol treatment and
      vice versa. RESULTS: At baseline, the average of ICP was 26.0 +/- 9.1 mmHg and
      the values of PRx were significantly correlated with ICP (p = 0.0044, r = 0.46).
      After mannitol administration, the average of ICP decreased significantly to 21.2
      +/- 11.1 mmHg (p = 0.036), and CVPR improved in 59.4 % of all events. Further
      analysis showed that low baseline cerebral perfusion pressure was the only
      hemodynamic parameter significant association with the improvement of CVPR after
      mannitol treatment (p = 0.039). CONCLUSION: Despite lowering ICP, mannitol may
      have diverse effects on CVPR in patients with intracranial hypertension. Our
      study suggests that mannitol infusion may have a beneficial effect on CVPR,
      particularly in those with a low cerebral perfusion pressure at baseline.

PMID- 24090637
TI  - Gender differences in CMS and the effects of antidepressant venlafaxine in rats.
AB  - Gender differences in susceptibility to chronic mild stress (CMS) and effects of
      venlafaxine in rats have been investigated in the current study. Male and female
      SD rats were exposed to CMS or CMS plus chronic venlafaxine administration
      (10mg/kg, 21days) in order to study depressive behavior in rats. Rats were tested
      in open field test and sucrose preference test to figure out gender differences
      in behavior. Then serum corticosterone and the expression of FKBP5 in hippocampus
      of rats were detected to explore the possible mechanism. The results showed that
      the CMS impact on behavioral parameters and corticosterone levels and response to
      venlafaxine were gender dependent. Female rats appeared more vulnerable in the
      dysregulation of HPA axis to CMS. Venlafaxine treatment normalized depressive
      like behavior in both gender. However, venlafaxine treated male rats exhibited
      better improved explore behavior and anhedonia. FKBP5 might be involved in the
      explanation of gender differences in CMS and venlafaxine treatment. Male and
      female rats respond differently to chronic stress and venlafaxine continuous
      treatment. This results have guiding meaning in design of trials related to
      stress induced depression. 

PMID- 24090639
TI  - Impaired posttranslational processing and trafficking of an endosomal Na+/H+
      exchanger NHE6 mutant (Delta(370)WST(372)) associated with X-linked intellectual
      disability and autism.
AB  - Na(+)/H(+) exchanger NHE6/SLC9A6 is an X-linked gene that is widely expressed and
      especially abundant in brain, heart and skeletal muscle where it is implicated in
      endosomal pH homeostasis and trafficking as well as maintenance of cell polarity.
      Recent genetic studies have identified several mutations in the coding region of
      NHE6 that are linked with severe intellectual disability, autistic behavior,
      ataxia and other abnormalities. One such defect consists of an in-frame deletion
      of three amino acids ((370)Trp-Ser-Thr(372), DeltaWST) that adjoin the predicted
      ninth transmembrane helix of the exchanger. To better understand the nature of
      this mutation, a NHE6DeltaWST construct was generated and assessed for its
      effects on the biochemical and cellular properties of the transporter. In
      transfected fibroblastic CHO and neuroblastoma SH-SY5Y cells, immunoblot analyses
      showed that the mutant protein was effectively synthesized, but its subsequent
      oligosaccharide maturation and overall half-life were dramatically reduced
      compared to wild-type. These changes correlated with significant accumulation of
      DeltaWST in the endoplasmic reticulum, with only minor sorting to the plasma
      membrane and negligible trafficking to recycling endosomes. The diminished
      accumulation in recycling endosomes was associated with a significant decrease in
      the rate of endocytosis of cell surface DeltaWST compared to wild-type.
      Furthermore, while ectopic expression of wild-type NHE6 enhanced the uptake of
      other vesicular cargo such as transferrin along the clathrin-mediated recycling
      endosomal pathway, this ability was lost in the DeltaWST mutant. Similarly, in
      transfected primary mouse hippocampal neurons, wild-type NHE6 was localized in
      discrete puncta throughout the soma and neurites, whereas the DeltaWST mutant
      displayed a diffuse reticular pattern. Remarkably, the extensive dendritic
      arborization observed in neurons expressing wild-type NHE6 was noticeably
      diminished in DeltaWST-transfectants. These results suggest that deletion of
      (370)Trp-Ser-Thr(372) leads to endoplasmic reticulum retention and loss of NHE6
      function which potentially impacts the trafficking of other membrane-bound cargo
      and cell polarity. 

PMID- 24090640
TI  - Molsidomine, a nitric oxide donor, modulates rotational behavior and monoamine
      metabolism in 6-OHDA lesioned rats treated chronically with L-DOPA.
AB  - Some biochemical and histological studies of Parkinson's disease patients' brains
      and 6-OHDA-lesioned rats suggest that dopaminergic dennervation of the striatum
      leads to the nitrergic system hypofunction in this structure. Hence, recently the
      modulation of nitric oxide (NO)- soluble guanylyl cyclase-cyclic GMP signaling is
      considered to be a new target for the treatment of Parkinson's disease. The aim
      of our study was to examine the impact of chronic combined treatment with low
      doses of the NO donor molsidomine (2 and 4mg/kg) and L-DOPA (12.5 and 25mg/kg) on
      rotational behavior and monoamine metabolism in the striatum (STR) and substantia
      nigra (SN) of unilaterally 6-OHDA-lesioned rats. Chronic administration of
      molsidomine at a dose of 2mg/kg jointly with 25mg/kg of L-DOPA significantly
      decreased the number of contralateral rotations when compared to L-DOPA alone.
      Other combinations of the examined drug doses were less effective. The tissue DA
      levels in the ipsilateral STR and SN after the last chronic doses of molsidomine
      (2mg/kg) and L-DOPA (12.5 or 25mg/kg), were significantly higher than after L
      DOPA alone. Chronic L-DOPA treatment alone or jointly with a lower dose of
      molsidomine decreased 5-HT levels and accelerated its catabolism in the examined
      structures. However, combination of a higher dose of molsidomine with L-DOPA
      (25mg/kg) did not reduce 5-HT content while its catabolism was less intensive.
      The obtained results show that low doses of molsidomine can modulate rotational
      behavior and tissue DA and 5-HT concentrations in the STR and SN of 6-OHDA
      lesioned rats treated chronically with L-DOPA. 

PMID- 24090638
TI  - Neuronal ablation of p-Akt at Ser473 leads to altered 5-HT1A/2A receptor
      function.
AB  - The serotonergic system regulates a wide range of behavior, including mood and
      impulsivity, and its dysregulation has been associated with mood disorders,
      autism spectrum disorder, and addiction. Diabetes is a risk factor for these
      conditions. Insulin resistance in the brain is specifically associated with
      susceptibility to psychostimulant abuse. Here, we examined whether
      phosphorylation of Akt, a key regulator of the insulin signaling pathway,
      controls serotonin (5-HT) signaling. To explore how impairment in Akt function
      regulates 5-HT homeostasis, we used a brain-specific rictor knockout (KO) mouse
      model of impaired neuronal phosphorylation of Akt at Ser473. Cortical 5-HT1A and
      5-HT2A receptor binding was significantly elevated in rictor KO mice. Concomitant
      with this elevated receptor expression, the 5-HT1A receptor agonist 8-Hydroxy-2
      (di-n-propylamino)tetralin (8-OH-DPAT) led to an increased hypothermic response
      in rictor KO mice. The increased cortical 5-HT1A receptor density was associated
      with higher 5-HT1A receptor levels on the cortical cell surface. In contrast,
      rictor KO mice displayed significantly reduced head-twitch response (HTR) to the
      5-HT2A/C agonist 2,5-dimethoxy-4-iodoamphetamine (DOI), with evidence of impaired
      5-HT2A/C receptor signaling. In vitro, pharmacological inhibition of Akt
      significantly increased 5-HT1A receptor expression and attenuated DOI-induced 5
      HT2A receptor signaling, thereby lending credence to the observed in vivo cross
      talk between neuronal Akt signaling and 5-HT receptor regulation. These data
      reveal that defective central Akt function alters 5-HT signaling as well as 5-HT
      associated behaviors, demonstrating a novel role for Akt in maintaining neuronal
      5-HT receptor function. 

PMID- 24090641
TI  - Tiotropium bromide inhibits relapsing allergic asthma in BALB/c mice.
AB  - Recurrent relapses of allergic lung inflammation in asthmatics may lead to airway
      remodeling and lung damage. We tested the efficacy of tiotropium bromide, a
      selective long-acting, muscarinic receptor antagonist as an adjunct therapy in
      relapses of allergic asthma in mice. We compared the effectiveness of local
      intranasal administration of tiotropium and dexamethasone in acute and relapsing
      allergic asthma in BALB/c mice. Although tiotropium at low doses is a potent
      bronchodilator, we tested higher doses to determine effectiveness on inflammation
      and mucus hypersecretion. A 5-day course of twice daily intranasal tiotropium or
      dexamethasone (1 mg/kg (b.w.)) suppressed airway eosinophils by over 87% during
      disease initiation and 88% at relapse compared to vehicle alone. Both drugs were
      comparable in their capacity to suppress airway and parenchymal inflammation and
      mucus hypersecretion, though tiotropium was better than dexamethasone at reducing
      mucus secretion during disease relapse. Despite treatment with either drug, serum
      antigen-specific IgE or IgG1 antibody titres remained unchanged. Our study
      indicates that tiotropium at higher doses than required for bronchodilation,
      effectively suppresses inflammation and mucus hypersecretion in the lungs and
      airways of mice during the initiation and relapse of asthma. Tiotropium is
      currently not approved for use in asthma. Clinical studies have to demonstrate
      the efficacy of tiotropium in this respiratory disease.

PMID- 24090642
TI  - Comparison of (bio-)transformation methods for the generation of metabolite-like
      compound libraries of p38alpha MAP kinase inhibitors using high-resolution
      screening.
AB  - Four hydrophobic p38alpha mitogen-activated protein kinase inhibitors were
      refluxed with 7.5% hydrogen peroxide at 80 degrees C and irradiated with visible
      light in order to generate more hydrophilic conversion products. The resulting
      mixtures were analyzed in a high-resolution screening (HRS) platform, featuring
      liquid chromatographic separation coupled in parallel with a fluorescence
      enhancement based continuous-flow affinity bioassay towards the p38alpha mitogen
      activated protein kinase and with high-resolution (tandem) mass spectrometry on
      an ion-trap-time-of-flight hybrid instrument. The results were compared with
      similar data where chemical diversity was achieved by means of electrochemical
      conversion or incubation with either human liver microsomes or cytochrome P450s
      from Bacillus megaterium (BM3s). In total, more than 50 conversion products were
      identified. The metabolite-like compound libraries studied are discussed in terms
      of the reactions enabled, the retention of affinity, and the change in
      hydrophilicity by modification, in summary the ability to generate bioactive,
      more hydrophilic potential lead compounds. In this context, HRS is demonstrated
      to be an effective tool as it reduces the effort directed towards laborious
      synthesis and purification schemes. 

PMID- 24090643
TI  - Treatment implications for men when switching from male to female bone mineral
      density reference data: the Manitoba Bone Density Program.
AB  - Since 2001, the International Society for Clinical Densitometry Official Position
      has been to use a young female normative database in women and a young male
      normative in men for T-scores. Several prospective studies have shown that men
      and women with identical hip bone mineral density (BMD) have the same fracture
      rates, and so there has been reconsideration of whether female reference data
      should be adopted for men. We studied 4691 men age 50 yr and older with baseline
      dual-energy X-ray absorptiometry assessments to explore how a change in BMD
      reference data from male to female would affect the number of men meeting
      National Osteoporosis Foundation (NOF) intervention criteria. We found that use
      of male vs female BMD reference data for T-score calculation did affect
      individual eligibility criteria for treatment under the NOF guidelines, but that
      overall differences in treatment rates were small when eligibility for treatment
      considered any of the NOF intervention criteria. Specifically, the majority of
      men who no longer qualified for treatment based upon T-scores calculated from
      female as opposed to male reference data would still qualify for treatment based
      upon other NOF intervention criteria. In addition, men only eligible for
      treatment under NOF criteria when using male reference data were at low fracture
      risk. We conclude that choice of male or female reference data for T-score
      calculation in men has little effect on overall treatment eligibility rates under
      NOF guidelines.

PMID- 24090644
TI  - Vitamin K and bone health.
AB  - Vitamin K has been purported to play an important role in bone health. It is
      required for the gamma-carboxylation of osteocalcin (the most abundant
      noncollagenous protein in bone), making osteocalcin functional. There are 2 main
      forms (vitamin K1 and vitamin K2), and they come from different sources and have
      different biological activities. Epidemiologic studies suggest a diet high in
      vitamin K is associated with a lower risk of hip fractures in aging men and
      women. However, randomized controlled trials of vitamin K1 or K2 supplementation
      in white populations did not increase bone mineral density at major skeletal
      sites. Supplementation with vitamin K1 and K2 may reduce the risk of fractures,
      but the trials that examined fractures as an outcome have methodological
      limitations. Large well-designed trials are needed to compare the efficacies of
      vitamin K1 and K2 on fractures. We conclude that currently there is not enough
      evidence to recommend the routine use of vitamin K supplements for the prevention
      of osteoporosis and fractures in postmenopausal women. 

PMID- 24090645
TI  - The Official Positions of the International Society for Clinical Densitometry:
      Indications of Use and Reporting of DXA for Body Composition.
AB  - The technique of body composition by dual-energy X-ray absorptiometry (DXA) has
      been used for several years in the research environment. Its ability to
      accurately and precisely measure lean, fat, and mineral composition in various
      body compartments has been well validated. Furthermore, the technique is widely
      available to clinical patients on existing DXA instruments throughout the world
      through the use of specific software packages and scanning algorithms. There have
      been few clear statements regarding the clinical indications for body composition
      measurement in patients outside the research setting. This is in part because of
      the lack of specific documented interventions that would be affected by body
      composition test results, beyond usual clinical advice. We have examined a few of
      the most common, specific scenarios (HIV therapy, sarcopenia, bariatric surgery,
      obesity) and proposed indications for body composition assessment. We have also
      discussed contraindications to body composition testing. 

PMID- 24090646
TI  - Celiac disease and metabolic bone disease.
AB  - Celiac disease is a common autoimmune gastrointestinal disorder affecting
      multiple organs, precipitated in genetically vulnerable persons by the ingestion
      of gluten. Gluten is poorly digested and is presented to the intestinal mucosa as
      a large polypeptide. Binding to human leukocyte antigen-DQ2 and human leukocyte
      antigen-DQ8 molecules on antigen-presenting cells stimulates cellular and humeral
      immune reactions. Although common serological tests are available to diagnose
      celiac disease, the diagnosis of celiac disease is often delayed or missed
      because of lack of recognition as the disease presentation in adults is highly
      variable and may be asymptomatic. Celiac disease is a common secondary cause of
      metabolic bone disease and delayed treatment with gluten-free diet affects bone
      mineral density and fracture risk, so it is crucial to diagnose and treat celiac
      disease promptly. In this article, we will review recent studies of celiac
      disease in adults and provide practical, easily accessible information for busy
      clinicians. 

PMID- 24090647
TI  - Phytoestrogens in the prevention of postmenopausal bone loss.
AB  - Postmenopausal osteoporosis is a condition associated with low bone mass
      resulting from the increased bone resorption that occurs following a decline in
      estrogen levels. Phytoestrogens are plant-derived compounds that have affinity to
      the estrogen receptor and are able to act as either estrogen agonists or
      antagonists. Because of their structural similarity to 17-beta-estradiol, they
      have been studied extensively for their role in the prevention of postmenopausal
      bone loss. An extensive number of studies employing different types of isoflavone
      preparations (including soy foods, soy-enriched foods, and soy isoflavone
      tablets) have been conducted in a wide range of populations, including Western
      and Asian women. Although there is considerable variability in study design and
      duration, study population, type of soy isoflavone employed in the intervention,
      and study outcomes, the evidence points to a lack of a protective role of soy
      isoflavones in the prevention of postmenopausal bone loss. 

PMID- 24090648
TI  - Pharmacokinetics of anidulafungin in two critically ill patients with septic
      shock undergoing CVVH.
AB  - Candidemia is associated with high mortality rate especially in critically ill
      (ICU) patients with septic shock and echinocandins such as anidulafungin are
      recommended as first-line treatment. Available pharmacokinetic studies of
      anidulafungin in healthy volunteers and in patients with renal or hepatic
      impairment showed that no dose adjustment is needed even in patients receiving
      standard intermittent haemodialysis. However, few data are available with
      continuous veno-venous haemofiltration (CVVH). In this study, the pharmacokinetic
      of anidulafungin was studied in two ICU patients with candidemia and septic shock
      undergoing CVVH. Both patients had satisfactory parameters of C(max) (9.04 and
      5.68 mg/l, respectively), area under the curve (AUC) (95.18 and 67.48 mg/l h) and
      C(min) (2.61 and 1.43 mg/l). AUC/MIC ratio and C(max)/MIC values were: 11887 and
      8435; 1130.25 and 710, for patients 1 and 2, respectively. Our data confirm that
      in patients with septic shock anidulafungin presents only mild pharmacokinetic
      changes compared to data reported during CVVH alone.

PMID- 24090649
TI  - Functional electrical stimulation post-spinal cord injury improves locomotion and
      increases afferent input into the central nervous system in rats.
AB  - BACKGROUND: Functional electrical stimulation (FES) has been found to be
      effective in restoring voluntary functions after spinal cord injury (SCI) and
      stroke. However, the central nervous system (CNS) changes that occur in as a
      result of this therapy are largely unknown. OBJECTIVE: To examine the effects of
      FES on the restoration of voluntary locomotor function of the CNS in a SCI rat
      model. METHODS: SCI rats were instrumented with chronic FES electrodes in the
      hindlimb muscles and were divided into two groups: (a) FES therapy and (b)
      sedentary. At day 7 post-SCI, the animals were assessed for locomotion
      performance by using a Basso, Beattie and Bresnahan (BBB) scale. They were then
      anesthetized for a terminal in vivo experiment. The lumbar spinal cord and
      somatosensory cortex were exposed and the instrumented muscles were stimulated
      electrically. Associated neurovascular responses in the CNS were recorded with an
      intrinsic optical imaging system. RESULTS: FES greatly improved locomotion
      recovery by day 7 post-SCI, as measured by BBB scores (P < 0.05): (a) FES 10 +/-
      2 and (b) controls 3 +/- 1. Furthermore, the FES group showed a significant
      increase (P < 0.05) of neurovascular activation in the spinal cord and
      somatosensory cortex when the muscles were stimulated between 1 and 3 motor
      threshold (MT). CONCLUSION: Hind limb rehabilitation with FES is an effective
      strategy to improve locomotion during the acute phase post-SCI. The results of
      this study indicate that after FES, the CNS preserves/acquires the capacity to
      respond to peripheral electrical stimulation.

PMID- 24090650
TI  - EPA protects against muscle damage in the mdx mouse model of Duchenne muscular
      dystrophy by promoting a shift from the M1 to M2 macrophage phenotype.
AB  - In dystrophic mdx mice and in Duchenne muscular dystrophy, inflammation
      contributes to myonecrosis. Previously, we demonstrated that eicosapentaenoic
      acid (EPA) decreased inflammation and necrosis in dystrophic muscle. In the
      present study, we examined the effects of EPA and the corticoid deflazacort (DFZ)
      as modulators of M1 (iNOS-expressing cells) and M2 (CD206-expressing cells)
      macrophages. Mdx mice (14 days old) received EPA or DFZ for 16 days. The
      diaphragm, biceps brachii and quadriceps muscles were studied.
      Immunofluorescence, immunoblotting and ELISA assays showed that EPA increased
      interleucin-10, reduced interferon-gamma and was more effective than DFZ in
      promoting a shift from M1 to M2.

PMID- 24090651
TI  - Interleukin-13/Interleukin-4-induced oxidative stress contributes to death of
      prothrombinkringle-2 (pKr-2)-activated microglia.
AB  - The present study examined whether Interleukin-13 (IL-13) or IL-4, an anti
      inflammatory cytokine, could induce cell death of activated microglia by
      prothrombin kringle-2 (pKr-2) which is a domain of prothrombin distinct from
      thrombin. Microglia cell death was detected at eight days after co-treatment of
      pKr-2 with IL-13/IL-4 in vitro. This cell death was assessed by live assay, dead
      assay, TUNEL and MTT assay. In parallel, reactive oxygen species (ROS) production
      was evident as assessed by superoxide assay, WST-1 and analyzing DCF in
      combination of pKr-2 and IL-13 or IL-4 treated microglia. The IL-13/IL-4-enhanced
      ROS production and cell death in pKr-2 activated microglia was partially
      inhibited by an NADPH oxidase inhibitor, apocynin and/or by several antioxidants.
      Moreover, Western blot analysis showed a significant increase in cyclooxygenase-2
      (COX-2) expression in combination of pKr-2 and IL-13 or IL-4 treated microglia,
      which was partially inhibited by apocynin and an antioxidant, trolox. Additional
      studies demonstrated that microglia cell death was reversed by treatment with COX
      2 inhibitor, NS398. Our data strongly suggest that oxidative stress and COX-2
      activation through NADPH oxidase may contribute to IL-13/IL-4 induced cell death
      of pKr-2 activated microglia. 

PMID- 24090654
TI  - An electrophysiologic approach to quantify impaired synaptic transmission and
      plasticity in experimental autoimmune encephalomyelitis.
AB  - Despite its various limitations, for many decades the experimental autoimmune
      encephalomyelitis (EAE) has been indispensable for understanding the pathology of
      multiple sclerosis (MS) and for establishing widely used MS therapeutics. We
      tested whether synaptic plasticity is a suitable measure for EAE and whether it
      can detect detrimental effects on supra-spinal structures that are too subtle to
      be captured by the motor score. Our data show functional synaptic deficits in the
      EAE that were beyond the measurable EAE score: long-term depression responses
      were strongly weakened in superior colliculus and cerebellum resulting from
      impaired postsynaptic transmission. In addition to further insight into neuronal
      deficits associated with the autoimmune disease, quantification of synaptic
      transmission may serve as a complementary method of EAE evaluation. 

PMID- 24090652
TI  - Potential role of A2A adenosine receptor in traumatic optic neuropathy.
AB  - In traumatic optic neuropathy (TON), apoptosis of retinal ganglion cells is
      closely related to the local production of reactive oxygen species and
      inflammatory mediators from activated microglial cells. Adenosine receptor A2A
      (A2AAR) has been shown to possess anti-inflammatory properties that have not been
      studied in TON. In the present study, we examined the role of A2AAR in retinal
      complications associated with TON. Initial studies in wild-type mice revealed
      that treatment with the A2AAR agonist resulted in marked decreases in the TON
      induced microglial activation, retinal cell death and releases of reactive oxygen
      species and pro-inflammatory cytokines TNF-alpha and IL-6. To further assess the
      role of A2AAR in TON, we studied the effects of A2AAR ablation on the TON-induced
      retinal abnormalities. A2AAR-/- mice with TON showed a significantly higher mRNA
      level of TNF-alpha, Iba1-1 in retinal tissue, and ICAM-1 expression in retinal
      sections compared with wild-type mice with TON. To explore a potential mechanism
      by which A2AAR-signaling regulates inflammation in TON, we performed additional
      studies using hypoxia- or LPS-treated microglial cells as an in vitro model for
      TON. Activation of A2AAR attenuates hypoxia or LPS-induced TNF-alpha release and
      significantly repressed the inflammatory signaling, ERK in the activated
      microglia. Collectively, this work provides pharmacological and genetic evidence
      for A2AAR signaling as a control point of cell death in TON and suggests that the
      retinal protective effect of A2AAR is mediated by attenuating the inflammatory
      response that occurs in microglia via interaction with MAPKinase pathway. 

PMID- 24090653
TI  - Effect of chronic morphine administration on circulating T cell population
      dynamics in rhesus macaques.
AB  - Opioid receptor agonists modulate both innate and adaptive immune responses. In
      this study, we examined the impact of long-term chronic morphine administration
      on the circulating T cell population dynamics in rhesus macaques. We found that
      the numbers of circulating Treg cells, and the functional activity of Th17 cells,
      were significantly increased with chronic morphine exposure. Our results also
      show that T cell populations with surface markers characteristic of gut-homing
      (CD161 and CCR6) and HIV-1 susceptibility (CCR5 and beta7 integrin) were
      increased. These results represent the first detailed report of the impact of
      chronic morphine administration on circulating T cell dynamics. 

PMID- 24090656
TI  - Off-label and unlicensed paediatric prescribing in a community setting: a
      prospective longitudinal cohort study in Malta.
AB  - BACKGROUND: In children, the incidence of off-label prescriptions in primary care
      varies between 10.5% and 22.7%, whilst the incidence of unlicensed prescriptions
      in primary care varies between 0.3% and 16.6%. This information has not been
      investigated in Malta. OBJECTIVE: To identify therapeutic areas which warrant
      research in children in the community setting in Malta according to the
      proportion and nature of off-label and unlicensed medicinal use. METHODS: Interim
      analysis involving the assessment of prescriptions for children in a prospective
      pharmacoepidemiological study. Data regarding prescriptions in 37 private clinics
      and pharmacies attended by paediatricians and family doctors were collected for a
      cohort of 209 patients aged 0-14 years. The medicines were categorised as
      licensed, unlicensed or off-label. They were also classified into various
      categories such as patient age-group, data collection period, prescriber type and
      Anatomical Therapeutic Chemical classification system. RESULTS: 113 of 209
      (54.1%) medicinal products were used in an off-label and unlicensed manner, the
      highest number being in the 2-11-years age range (76/209). The majority of drugs
      were for the respiratory system. The proportion off-label drug prescribing
      because of age decreased progressively with increasing age whilst the proportion
      off-label prescribing because of dose increased with age. CONCLUSION: The main
      cause of off-label prescribing appears to be a failure to adhere to licensed dose
      recommendations and a lack of agreement between the existing literature and drug
      licences.

PMID- 24090655
TI  - Immature mesenchymal stem cell-like pericytes as mediators of immunosuppression
      in human malignant glioma.
AB  - Malignant gliomas are primary brain tumors characterized by profound local
      immunosuppression. While the remarkable plasticity of perivascular cells -
      resembling mesenchymal stem cells (MSC) - in malignant gliomas and their
      contribution to angiogenesis is increasingly recognized, their role as potential
      mediators of immunosuppression is unknown. Here we demonstrate that FACS-sorted
      malignant glioma-derived pericytes (HMGP) were characterized by the expression of
      CD90, CD248, and platelet-derived growth factor receptor-beta (PDGFR-beta). HMGP
      shared this expression profile with human brain vascular pericytes (HBVP) and
      human MSC (HMSC) but not human cerebral microvascular endothelial cells (HCMEC).
      CD90+PDGFR-beta+perivascular cells distinct from CD31+ endothelial cells
      accumulated in human gliomas with increasing degree of malignancy and negatively
      correlated with the presence of blood vessel-associated leukocytes and CD8+ T
      cells. Cultured CD90+PDGFR-beta+HBVP were equally capable of suppressing
      allogeneic or mitogen-activated T cell responses as human MSC. HMGP, HBVP and
      HMSC expressed prostaglandin E synthase (PGES), inducible nitric oxide synthase
      (iNOS), human leukocyte antigen-G (HLA-G), hepatocyte growth factor (HGF) and
      transforming growth factor-beta (TGF-beta). These factors but not indoleamine 2,3
      dioxygenase-mediated conversion of tryptophan to kynurenine functionally
      contributed to immunosuppression of immature pericytes. Our data provide evidence
      that human cerebral CD90+ perivascular cells possess T cell inhibitory capability
      comparable to human MSC and suggest that these cells, besides their critical role
      in tumor vascularization, also promote local immunosuppression in malignant
      gliomas and possibly other brain diseases. 

PMID- 24090657
TI  - RNA and splicing regulation in neurodegeneration.

PMID- 24090659
TI  - Multifunctional weaponry: the chemical defenses of earwigs.
AB  - Earwigs protect themselves against predators using pincer-like cerci and/or
      malodorous exudates secreted from abdominal glands. Little is known about the
      chemistry of these secretions and their potential functions. However, because
      earwigs live in aggregations and overwinter in soil, they are exposed to high
      microbial loads throughout their lifecycle, and we therefore hypothesized that
      the secretions are used not only to deter predators but also to combat pathogens
      and parasites in their environment. We analyzed the defensive secretions of the
      European earwig Forficula auricularia, the short-winged earwig Apterygida media
      and the woodland earwig Chelidurella guentheri by gas chromatography-mass
      spectrometry. The secretions of all three species contained 2-methyl-1,4
      benzoquinone and 2-ethyl-1,4-benzoquinone, whereas A. media also produced 2,3
      dimethyl-1,4-benzoquinone and 2-ethyl-3-methyl-1,4-benzoquinone. The latter has
      not been identified in the exudates of insects before. The composition and/or
      quantity of these components were species-specific and partially sex-specific.
      All secretions showed antimicrobial activity against Gram-positive and Gram
      negative bacteria as well as two entomopathogenic fungi. Furthermore, the
      secretion of F. auricularia displayed nematicidal activity against Caenorhabditis
      elegans. Our data support the hypothesis that earwig secretions are
      multifunctional, serving both to deter predators and sanitize the
      microenvironment. 

PMID- 24090658
TI  - The Gdac1 locus modifies spontaneous and Salmonella-induced colitis in mice
      deficient in either Gpx2 or Gpx1 gene.
AB  - We previously identified the Gdac1 (Gpx-deficiency-associated colitis 1) locus,
      which influences the severity of spontaneous colitis in Gpx1- and Gpx2-double
      knockout (Gpx1/2-DKO) mice. Congenic Gpx1/2-DKO mice in the 129S1/SvImJ (129)
      background but carrying the Gdac1(B6) allele have milder spontaneous colitis than
      129 Gpx1/2-DKO mice carrying the Gdac1(129) allele. Here, we evaluated the effect
      of the Gdac1(B6) allele on 129 strain non-DKO mice that had a wild-type (WT) Gpx1
      or Gpx2 allele and WT mice. We found that the congenic Gdac1(B6) Gpx2-KO, Gpx1
      KO, and WT mice also had better health than the corresponding 129 mice measured
      by at least one of the parameters including disease signs, colon length, or
      weight gain. The Gdac1(B6) allele prevented loss of goblet cells and crypt
      epithelium exfoliation in the Gpx1/2-DKO mice, but did not affect epithelial cell
      apoptosis or proliferation. Because Gdac1(B6) affects gut dysbiosis in the DKO
      mice, we then tested its impact on bacteria-induced colitis in non-DKO mice.
      First, we found both Gpx1-KO and Gpx2-KO mice were susceptible to Salmonella
      enterica serotype typhimurium (S. Tm)-induced colitis under conditions where WT
      B6 and 129 mice were resistant. Second, the S. Tm-infected Gdac1(B6) Gpx1-KO mice
      had stronger inflammatory responses than 129 Gpx1-KO or 129 Gpx2-KO with both
      Gdac1 alleles and WT mice by having higher mRNA levels of Nod2, Nox2, Tnf, and
      Cox2. We conclude that the Gdac1 locus affects both spontaneous and S. Tm-induced
      colitis in 129 non-DKO mice, although in opposite directions. 

PMID- 24090660
TI  - Long-term outcome of a metal-on-polyethylene cementless hip resurfacing.
AB  - Due to the well-documented problems surrounding metal-on-metal bearings, the use
      of hip resurfacing has declined. Since the potential benefits of hip resurfacing
      remain desirable, it may be beneficial to investigate the long-term outcome of
      hip resurfacings using metal-on-polyethylene in the 1980's. We report the long
      term survivorship and modes of failure of a cementless metal-on-polyethylene
      resurfacing (n = 178) with different porous ingrowth surfaces. While acetabular
      loosening was absent, a high incidence of femoral failures (femoral loosening =
      18.1%, osteolytic neck fracture = 21%) occurred despite using the same ingrowth
      surface for both components. Ongoing developments using the lessons learned from
      these previous generation components and utilizing modern low wear materials,
      e.g., cross-linked polyethylene, may lead to improved implants for future hip
      resurfacings.

PMID- 24090661
TI  - Modular taper junction corrosion and failure: how to approach a recalled total
      hip arthroplasty implant.
AB  - Corrosion at the modular neck-stem taper junction has become an increasingly
      important topic as several reports have identified this couple as a possible
      source for early failure with findings similar to failed metal-on-metal hip
      arthroplasties. Recently, two different modular stem systems from a single
      manufacturer were voluntarily recalled due to concerns of failure of the modular
      taper junction. We discuss how to approach the diagnosis and management of
      patients with these particular stem systems. We further reviewed the literature
      to evaluate whether this is a manufacturer-specific defect or indicative of a
      broader trend. Recent studies appear to implicate the basic design of the neck
      stem taper junction, rather than a single manufacturer, which is at high risk for
      fretting and corrosion. 

PMID- 24090662
TI  - Depression is associated with early postoperative outcomes following total joint
      arthroplasty: a nationwide database study.
AB  - The purpose of this study was to assess the incidence of the diagnosis of
      depression and determine the impact of this diagnosis on early postoperative
      outcomes following total joint arthroplasty (TJA). Multivariate analysis of the
      Nationwide Inpatient Sample database was used to compare the association of
      depression with inhospital morbidity, mortality, length of stay, and hospital
      charges following TJA. The rate of diagnosis of depression in the arthroplasty
      population was 10.0%. Patients with depression were significantly more likely to
      be white, female, and have Medicaid as a primary payer (all P<0.05). Depression
      was associated with a greater risk of post-operative psychosis (OR = 1.74),
      anemia (OR = 1.14), infection (OR = 1.33), and pulmonary embolism (OR 1.20), and
      a lower risk of cardiac (OR = 0.93) and gastrointestinal complications (OR =
      0.80). Depression was not associated with in-hospital mortality. Depression
      appears to impact early postoperative morbidity after TJA, a finding which is
      important for patient counseling and risk adjustment.

PMID- 24090663
TI  - Tobacco use may be associated with increased revision and complication rates
      following total hip arthroplasty.
AB  - The purpose of this study was to compare the clinical outcomes of total hip
      arthroplasty in patients who were smokers to patients who were non-smokers. All
      total hip arthroplasties performed between 2007 and 2009 were reviewed to
      identify patients who indicated tobacco use. There were 110 smokers who were
      matched in a 1:2 ratio to 220 non-smoking patients. At a mean follow-up of 51
      months (range, 24 to 72 months), smokers had an overall significantly lower
      survivorship of 92% (n = 9 revisions), compared to 99% (n = 2 revisions) in non
      smokers. In addition, there were five complications in smokers (one pneumonia,
      three superficial infections, and one deep peroneal nerve palsy) compared to none
      in non-smokers. These results indicate that patients who smoke had higher overall
      revisions and postoperative complications.

PMID- 24090664
TI  - Insulin analogues may accelerate progression of diabetic retinopathy after
      impairment of inner blood-retinal barrier.
AB  - Diabetic retinopathy regresses after spontaneous infarction or surgical ablation
      of pituitary gland. Growth hormone deficiency seems to be a protective factor for
      development of diabetic retinopathy in dwarfs. Despite the same glycemic control,
      development of diabetic retinopathy is significantly higher in pubertal subjects
      than pre-pubertal subjects. These evidences indicate a strong relationship
      between growth hormone and progression of diabetic retinopathy. Insulin like
      growth factor-1 (IGF-1) is the most important mediator of effects of growth
      hormone (GH). It stimulates IGF-1 receptor. Insulin analogues also stimulate IGF
      1 receptor. Therefore insulin analogues may show similar effects like growth
      hormone and deteriorate diabetic retinopathy. However we suggest that impairment
      degree of inner blood-retinal barrier should be considered for this claim. We
      hypothesize that insulin analogues have dual effects (beneficial and worsening)
      depending on stage of impairment of inner blood-retinal barrier. Insulin
      analogues protect pericytes and blood-retinal barrier by decreasing blood glucose
      level. Analogues may pass into the retinal tissue in very low amounts when inner
      blood-retinal barrier is intact. Therefore, insulin analogues may not deteriorate
      diabetic retinopathy but also have beneficial effect by protecting blood-retinal
      barrier at this stage. However, they may pass into the retinal tissue in much
      more amounts when inner blood-retinal barrier impairs. Analogues may deteriorate
      cellular composition of retina through stimulation of IGF-1 receptors. A number
      of different cell types, including glia, retinal pigment epithelial cells and
      fibroblast-like cells have been identified in diabetic epiretinal tissues.
      Insulin analogues may cause proliferation in these cells. A type of glial cell
      named Non-astrocytic Inner Retinal Glia-like (NIRG) cell was identified to be
      stimulated and proliferate by IGF-1. IGF has been reported to generate traction
      force in retinal pigment epitelium (RPE) and mullerian cells. Mullerian cells
      also support inner blood-retinal barrier. Insulin analogues may cause
      proliferation in glial cells and generate traction force in RPE and mullerian
      cells by stimulating IGF-1 receptor. These effects of analogues may increase
      after deterioration of inner blood-retinal barrier and cause structural changes
      in retinal tissue. Deterioration of cellular structure may contribute to
      impairment of inner blood-retinal barrier, facilitate anjiogenesis and influence
      vitreoretinal interface. Therefore we suggest that insulin analogues should be
      used carefully after impairment of inner blood-retinal barrier. Analogues that
      bind with lesser affinity to IGF-1 receptor should be chosen after impairment.
      Pharmacologic agents may be developed to antagonize effect of insulin analogues
      on IGF-1 receptors. 

PMID- 24090665
TI  - [Bullous contact allergy induced by temporary black henna tattoo].

PMID- 24090666
TI  - [Anti-NMDAR paraneoplastic encephalitis].

PMID- 24090667
TI  - [Management of acute infantile diarrhea in integrated health centers in
      Brazzaville, Congo].

PMID- 24090668
TI  - [Bulimia during adolescence].
AB  - Binge eating, bulimia nervosa, binge eating disorder, anorexia-bulimia are terms
      often used without really knowing what precisely one is referring to. Otherwise,
      there are many articles concerning anorexia nervosa in medical literature, a
      disease, which can be seen and fascinates. These eating disorders are frequent in
      today's society; medical, psychological and social consequences are important. 

PMID- 24090669
TI  - [Familial congenital hypomagnesemia revealed by neonatal convulsions].
AB  - Congenital hypomagnesemia is a rare disease, with an impact on cognitive and
      neurological development. We report on three familial cases of congenital
      hypomagnesemia, two boys and one girl who belong to the same consanguineous
      family. They all presented neonatal seizures and a psychomotor developmental
      delay. Cerebral computed tomography showed cerebral atrophy and calcifications in
      one case and magnetic resonance imaging found predominant cerebellar atrophy in
      the two other cases. All three patients also had hypocalcemia, hyperphosphoremia,
      and hypomagnesemia. The parathyroid hormone blood level was low in two cases and
      normal in the third. One 7-month old patient died. The others received a
      supplementation of calcium and magnesium, which normalized calcemia, phosphatemia
      but not magnesemia, which remained low despite high doses. They have both
      developed cognitive and behavioral impairments. 

PMID- 24090670
TI  - [Prevalence of overweight preschool-age children: medical examination data of
      schoolchildren in southwestern France].
AB  - OBJECTIVE: To analyze anthropometric data in a sample of 3- to 4-year-old
      children examined by Mother and Infant Welfare in preschools in the Haute-Garonne
      area of France. PATIENTS AND METHODS: Two consecutive school years (2007-2008 and
      2008-2009) were analyzed. The samples studied included 5470 children the first
      year (mean age +/- standard deviation : 3.9+/-0.4 years) and 4088 children the
      second year (4.0+/-0.4 years). Prevalence of overweight (defined according to
      International Obesity Task Force references) and its association with various
      factors (sex, age, and school location) were studied. RESULTS: Prevalence of
      overweight (including obesity) was 8.4% for the 2 years, with a prevalence of
      obesity of 1.8% in 2007-2008 and of 1.6% in 2008-2009. Overweight was
      significantly more frequent in girls than in boys (10.2% vs. 6.8% in 2007-2008
      and 9.7% vs. 7.2% in 2008-2009) and in schools located in Priority Education
      Zones (ZEP) compared to schools in non-ZEP schools (17.9% vs. 7.1% in 2007-2008
      and 15.7% vs. 7.2% in 2008-2009). CONCLUSION: This analysis will be repeated to
      follow the prevalence of overweight in children. These preliminary results
      confirm the need to focus on preventive actions, screening and care for
      overweight and obesity in underprivileged populations.

PMID- 24090671
TI  - [Clinical signs of Marfan syndrome in children under 10 years of age].
AB  - Diagnosing Marfan syndrome in young children is difficult because of the great
      variability of expression of the disease and because the phenotype evolves over
      the life course. The goal of this retrospective study was to describe the first
      clinical symptoms in children under 10 years of age with Marfan syndrome and to
      evaluate the pertinence of the new 2010 Ghent criteria in comparison with the
      1996 criteria. Seventeen patients under 10 by the time of the first medical
      examination were included. All children had an FBN1 gene mutation that was
      secondarily demonstrated. Clinical data including ophthalmological, cardiac, and
      orthopaedic examinations obtained during the first medical examination were
      analyzed. The most frequent abnormalities encountered were high arched palate
      (82%), arachnodactyly (71%), and flatfoot (59%). Aortic aneurysm (47%) and
      ectopic lens (35%) were also seen at the time of diagnosis. According to the 2010
      Ghent criteria, the diagnosis of Marfan syndrome could be obtained in 71% of
      patients after identification of the mutation of the FBN1 gene, whereas only 59%
      of patients were diagnosed using the older criteria. All organs can be affected
      during childhood. An early diagnosis is essential in order to set up specific
      management. 

PMID- 24090672
TI  - Single step 18F-labeling of dimeric cycloRGD for functional PET imaging of tumors
      in mice.
AB  - INTRODUCTION: Arylboronates afford rapid aqueous (18)F-labeling via the creation
      of a highly polar (18)F-aryltrifluoroborate anion ((18)F-ArBF3(-)). HYPOTHESIS:
      Radiosynthesis of an (18)F-ArBF3(-) can be successfully applied to a clinically
      relevant peptide. To test this hypothesis, we labeled dimeric-cylcoRGD,
      [c(RGDfK)]2E because a) it is molecularly complex and provides a challenging
      substrate to test the application of this technique, and b) [c(RGDfK)]2E has
      already been labeled via several (18)F-labeling methods which provide for a
      preliminary comparison. GOAL: To validate this labeling method in the context of
      a complex and clinically relevant tracer to show tumor-specific uptake ex vivo
      with representative PET images in vivo. METHODS: An arylborimidine was conjugated
      to [c(RGDfK)]2E to give the precursor [c(RGDfK)]2E-ArB(dan), which was aliquoted
      and stored at -20  degrees C. Aliquots of 10 or 25 nmol, containing only
      micrograms of precursor, were labeled using relatively low levels of (18)F
      activity. Following purification eight mice (pre-blocked/unblocked) with U87M
      xenograft tumors were injected with [c(RGDfK)]2E-(18)F-ArBF3(-) (n = 4) for ex
      vivo tissue dissection. Two sets of mice (pre-blocked/unblocked) were also imaged
      with PET-CT (n = 2). RESULTS: The [c(RGDfK)]2E-ArB(dan) is converted within 15
      min to [c(RGDfK)]2E-(18)F-ArBF3(-) in isolated radiochemical yields of ~10% (n =
      3) at a minimum effective specific activity of 0.3 Ci/MUmol. Biodistribution
      shows rapid clearance to the bladder via the kidney resulting in high tumor-to
      blood and tumor-to-muscle ratios of >9 and >6 respectively while pre-blocking
      with [c(RGDfK)]2E showed high tumor specificity. PET imaging showed good contrast
      between tumor and non-target tissues confirming the biodistribution data.
      CONCLUSION: An arylborimidine-RGD peptide is rapidly (18)F-labeled in one step,
      in good yield, at useful specific activity. Biodistribution studies with blocking
      controls show tumor specificity, which is corroborated by PET images. Advances in
      Knowledge and Implications for patient Care: Despite many antecedent examples of
      labeled RGD tracers, this work is the first to show direct aqueous labeling of
      bisRGD with an (18)F-ArBF3(-). Labeling occurs in near record rapidity (45 min)
      at useful effective specific activities and competitive yields for high contrast
      tumor specific images. As bisRGD has been imaged in humans with several
      prosthetics, this work suggests potential clinical applications of tracers
      appended with an (18)F-ArBF3(-). More generally, the ability to label a
      molecularly complex tracer suggests that this method could be useful to label
      many other peptides. Furthermore, these results portend the development of kits
      that use only microgram quantities of lyophilized precursor for on demand
      labeling. The ability to perform one-step aqueous labeling in under an hour to
      provide tracers with high T:NT ratios has important implications for developing
      radiotracers for use in fundamental research and in preclinical tracer studies.

PMID- 24090673
TI  - Adrenergic pathway activation enhances brown adipose tissue metabolism: a
      [18F]FDG PET/CT study in mice.
AB  - OBJECTIVE: Pharmacologic approaches to study brown adipocyte activation in vivo
      with a potential of being translational to humans are desired. The aim of this
      study was to examine pre- and postsynaptic targeting of adrenergic system for
      enhancing brown adipose tissue (BAT) metabolism quantifiable by [(18)F]fluoro-2
      deoxyglucose ([(18)F]FDG) positron emission tomography (PET)/computed tomography
      (CT) in mice. METHODS: A beta3-adrenoreceptor selective agonist (CL 316243), an
      adenylyl cyclase enzyme activator (forskolin) and a potent blocker of presynaptic
      norepinephrine transporter (atomoxetine), were injected through the tail vein of
      Swiss Webster mice 30 minutes before intravenous (iv) administration of
      [(18)F]FDG. The mice were placed on the PET/CT bed for 30 min PET acquisition
      followed by 10 min CT acquisition for attenuation correction and anatomical
      delineation of PET images. RESULTS: Activated interscapular (IBAT), cervical,
      periaortic and intercostal BAT were observed in 3-dimentional analysis of
      [(18)F]FDG PET images. CL 316243 increased the total [(18)F]FDG standard uptake
      value (SUV) of IBAT 5-fold greater compared to that in placebo-treated mice. It
      also increased the [(18)F]FDG SUV of white adipose tissue (2.4-fold), and muscle
      (2.7-fold), as compared to the control. There was no significant difference in
      heart, brain, spleen and liver uptakes between groups. Forskolin increased
      [(18)F]FDG SUV of IBAT 1.9-fold greater than that in placebo-treated mice. It
      also increased the [(18)F]FDG SUV of white adipose tissue (2.2-fold) and heart
      (5.4-fold) compared to control. There was no significant difference in muscle,
      brain, spleen, and liver uptakes between groups. Atomoxetine increased [(18)F]FDG
      SUV of IBAT 1.7-fold greater than that in placebo-treated mice. There were no
      significant differences in all other organs compared to placebo-treated mice
      except liver (1.6 fold increase). A positive correlation between SUV levels of
      IBAT and CT Hounsfield unit (HU) (R(2)=0.55, p<0.001) and between CT HU levels of
      IBAT and liver (R(2)=0.69, p<0.006) was observed. CONCLUSIONS: The three
      pharmacologic approaches reported here enhanced BAT metabolism by targeting
      different sites in adrenergic system as measured by [(18)F]FDG PET/CT.

PMID- 24090674
TI  - Phase II study of S-1 monotherapy in patients over 75 years of age with advanced
      gastric cancer (OGSG0404).
AB  - BACKGROUND: S-1+cisplatin (CDDP) is the standard treatment for advanced gastric
      cancer (AGC) in Japan and Korea. However, the usefulness of S-1 based
      chemotherapy for elderly patients is unclear. Therefore, we conducted a
      multicenter phase II study of S-1 monotherapy for AGC in elderly patients.
      MATERIALS AND METHODS: Chemotherapy-naive patients aged over 75 years with AGC
      were enrolled. The starting dose of S-1 was determined on the basis of body
      surface area and modified according to the creatinine clearance value. S-1 was
      administered twice a day during a 4-week period followed by a 2-week rest period.
      RESULTS: Thirty-five patients were enrolled. The response rate (RR) was 14.3% and
      the median overall survival was 14.6 months. Grade 3 or more severe adverse
      events consisted of anaemia (3%), neutropaenia (3%), anorexia (3%), and fatigue
      (6%). There were no treatment-related deaths. CONCLUSION: Our study indicates
      that S-1 monotherapy is safe and well tolerated in chemotherapy-naive elderly
      patients with AGC, but exerts limited activity when given using a tailor-made
      dosing strategy based on renal function.

PMID- 24090676
TI  - Moxifloxacin in lower respiratory tract infections: in silico simulation of
      different bacterial resistance and drug exposure scenarios.
AB  - Moxifloxacin has potent bactericidal activity against Streptococcus pneumoniae; a
      major causative organism of lower respiratory tract infections. This study aims
      to use the pharmacokinetic/pharmacodynamic indices to predict the therapeutic
      outcome under different scenarios of moxifloxacin exposure and pneumococcal
      resistance. STELLA((r)) software was used to simulate the pharmacokinetics and
      pharmacodynamics of moxifloxacin in patients with severe pneumonia and acute
      exacerbations of chronic bronchitis (AECB). The current dose of moxifloxacin was
      found to be insufficient for eradication of ciprofloxacin resistant bacteria in
      ventilated patients with severe bronchopneumonia. This can be attributed to the
      lower tissue penetration observed in this population. Increasing the dose to 600
      mg was able to achieve higher levels of free drug AUC/MIC in both bronchial and
      plasma compartments. In AECB, moxifloxacin achieved the same AUC/MIC values
      observed in pneumonia at the different MIC values. This may allow the
      extrapolation of findings of moxifloxacin studies in pneumonia to the management
      of patients with AECB. 

PMID- 24090675
TI  - SLIT3-ROBO4 activation promotes vascular network formation in human engineered
      tissue and angiogenesis in vivo.
AB  - Successful implantation and long-term survival of engineered tissue grafts hinges
      on adequate vascularization of the implant. Endothelial cells are essential for
      patterning vascular structures, but they require supportive mural cells such as
      pericytes/mesenchymal stem cells (MSCs) to generate stable, functional blood
      vessels. While there is evidence that the angiogenic effect of MSCs is mediated
      via the secretion of paracrine signals, the identity of these signals is unknown.
      By utilizing two functionally distinct human MSC clones, we found that so-called
      "pericytic" MSCs secrete the pro-angiogenic vascular guidance molecule SLIT3,
      which guides vascular development by directing ROBO4-positive endothelial cells
      to form networks in engineered tissue. In contrast, "non-pericytic" MSCs exhibit
      reduced activation of the SLIT3/ROBO4 pathway and do not support vascular
      networks. Using live cell imaging of organizing 3D vascular networks, we show
      that siRNA knockdown of SLIT3 in MSCs leads to disorganized clustering of ECs.
      Knockdown of its receptor ROBO4 in ECs abolishes the generation of functional
      human blood vessels in an in vivo xenogenic implant. These data suggest that the
      SLIT3/ROBO4 pathway is required for MSC-guided vascularization in engineered
      tissues. Heterogeneity of SLIT3 expression may underlie the variable clinical
      success of MSCs for tissue repair applications. 

PMID- 24090677
TI  - In the time of significant generational diversity - surgical leadership must step
      up!
AB  - The diverse attitudes and motivations of surgeons and surgical trainees within
      different age groups present an important challenge for surgical leaders and
      educators. These challenges to surgical leadership are not unique, and other
      industries have likewise needed to grapple with how best to manage these various
      age groups. The authors will herein explore management and leadership for
      surgeons in a time of age diversity, define generational variations within "Baby
      Boomer", "Generation X" and "Generation Y" populations, and identify work ethos
      concepts amongst these three groups. The surgical community must understand and
      embrace these concepts in order to continue to attract a stellar pool of
      applicants from medical school. By not accepting the changing attitudes and
      motivations of young trainees and medical students, we may disenfranchise a high
      percentage of potential future surgeons. Surgical training programs will fill,
      but will they contain the highest quality trainees? 

PMID- 24090678
TI  - The Mannerfelt wrist arthrodesis - a study of patient-reported outcomes in a
      rheumatoid population.
AB  - BACKGROUND: Wrist arthrodesis has been established as a mainstay form of surgical
      intervention in the rheumatoid wrist. Despite this however, there is a distinct
      lack of patient-reported outcome measure (PROM) studies justifying the efficacy
      of this procedure in rheumatoid disease. The aim of this study was to report any
      change in function or pain following the tunnel Mannerfelt wrist arthrodesis in a
      single surgeon series of rheumatoid patients over a 6 year period. METHODS: 14
      consecutive patients (15 wrists) who had undergone the Mannerfelt wrist
      arthrodesis were followed prospectively with a mean follow up period of 45
      months. No patients were lost to follow up. The primary outcome measures included
      the validated Patient Rated Wrist Evaluation (PRWE) questionnaire and a
      satisfaction questionnaire. RESULTS: The mean total pain score improved from 41
      points preoperatively to 14.2 points postoperatively correlating with a 65.4%
      improvement in overall pain outcomes. The mean total functional score improved
      from 83.7 points preoperatively to 45.5 points postoperatively demonstrating a
      45.6% improvement in overall function at the time of follow up. CONCLUSIONS: All
      patients reported an overall improvement in pain and functional capacity. The
      satisfaction results were excellent. All patients reported that they would elect
      to have the procedure again with the vast majority being 'very pleased' with the
      outcome of their surgery (93.7% very pleased and 6.3% fairly pleased). The
      procedure enjoyed favourable mid-term results and we recommend the tunnel
      Mannerfelt wrist arthrodesis for improving both pain and level of function in
      this group of patients.

PMID- 24090679
TI  - Severe slipped upper femoral epiphysis; fish osteotomy versus pinning-in-situ: an
      eleven year perspective.
AB  - PURPOSE: Slipped upper femoral epiphysis (SUFE) is not common with a reported
      incidence of 10 per 100 000. The management of SUFE is controversial and
      evolving, with advancing surgical skills and expertise. The infrequency of cases,
      the various classifications in use, the various surgical treatments, and lack of
      robust evidence for outcomes, has resulted in the lack of clear, evidence-based
      recommendations for treatment. Although mild slip can be treated with pinning-in
      situ (PIS) with predictably good outcome, moderate and severe slips present a
      challenge for the treating surgeons. It is logical to reduce the slip to near
      anatomical position; however, this desire has always been tempered by concerns
      about the potentially devastating complications of osteonecrosis and Chondrolysis
      METHODS: This is a single centre, retrospective study comparing (PIS) and Fish
      femoral neck osteotomy. Seventy four children presented with SUFE (90 hips). The
      mild and the moderate groups were treated with a single pining-in-situ (PIS). The
      severe group had either a surgical reduction by Fish femoral neck osteotomy or
      PIS. The study was approved by the regional and local ethic committee.
      Demographic data, clinical findings, radiographic features were collected.
      RESULTS: Avascular necrosis of the femoral head (osteonecrosis) was the primary
      outcome. There were 11 cases of osteonecrosis (12.2%): 3/41(6.9%) in the stable
      group compared to 7/22 (31.8%) in the unstable group, statistically significant
      [P < 0.001]. In the severe slip group, the osteonecrosis rate was 33.3% in the
      PIS group and 26.6% in the Fish osteotomy (P = 0.539). This is not statistically
      significant, but the trend favours surgical reduction. CONCLUSIONS: Then
      reduction of the deformity is valuable. The majority of cases that do not suffer
      osteonecrosis will benefit by reduction of the deformity; those who are destined
      to develop osteonecrosis are still better off with the femoral head in a reduced
      position. The unstable slip is more likely to be severe and more likely therefore
      to receive surgical reduction than a stable and less severe hip. The implication
      here is that the osteotomy might not be the cause of the osteonecrosis; it is the
      vascular damage due to the instability of the slip that is responsible.

PMID- 24090680
TI  - Smart consultation for musculoskeletal trauma: accuracy of using smart phones for
      fracture diagnosis.
AB  - INTRODUCTION: Musculoskeletal trauma occupies a significant proportion of the
      daily workload of most Emergency and Radiology departments. The diagnosis and
      management of patients with musculoskeletal trauma often require assessment of
      radiographs along with clinical assessment. With the advent of smart phones we
      hypothesised that they could be used as a means of smarter communication,
      particularly for the transfer of radiographic images between healthcare
      professionals. PATIENTS AND METHOD: We performed a cross sectional study using
      thirty radiographs each of the distal radius, ankle and hip. The study was
      approved by Ethics Committee and all data were anonymized in accordance to
      Caldicott guidelines and data protection act 1998. Photographs of radiographs
      were taken using an iphone camera and sent to three independent Orthopaedic
      Registrars via Multimedia messaging service (MMS). Each Registrar independently
      assessed these images on their smart phone display in their own time and recorded
      the specific diagnosis along with the classification of fractures and specific
      treatment plan. The accuracy of diagnosis on smart phone was measured against the
      radiology report; and inter observer agreement was assessed among registrars for
      classification and treatment plan. RESULTS: The overall accuracy of fracture
      diagnosis was 97.7% with sensitivity of 100% and specificity of 94.4%. The inter
      observer agreement analysis showed kappa (k) values of 0.67, 0.67 and 0.71 for
      classification of wrist, ankle and hip fractures respectively showing substantial
      agreement while kappa values for management plan were 0.65, 0.88 and 0.65 for the
      three fractures respectively showing substantial to near perfect agreement.
      CONCLUSION: This study suggests that smart phone can be used as a safe and
      accurate tool for skeletal trauma consultation among oncall doctors and can help
      reduce the waiting time in emergency departments.

PMID- 24090681
TI  - Identification of serum component involved in generation of neo-lectin with
      agglutinating and phenoloxidase activities in human serum.
AB  - Human serum albumin (HSA) was identified as the component involved in generation
      of neo-lectin molecules with both lectin and phenoloxidase activities. Pronase
      treated HSA was able to agglutinate hen RBC and oxidize hydroquinone. Sodium
      dodecyl sulphate (SDS) treated HSA agglutinated both hen and sheep RBC as well as
      oxidized dopamine. The hemagglutinating activities of pronase/SDS treated HSA
      observed against hen RBC were dosimetric. The oxidation of pronase/SDS treated
      HSA with hydroquinone/dopamine, respectively, was inhibitable by inhibitors of
      phenoloxidase, namely, phenylthiourea and tropolone. Very low concentrations of
      HSA could generate these humoral neo-lectin molecules. 

PMID- 24090682
TI  - The proportion and function of peripheral myeloid-derived suppressor cells do not
      correlate with systemic inflammation in chronic obstructive pulmonary disease.
AB  - Myeloid-derived suppressor cells (MDSC) have been implicated in the regulation of
      chronic inflammation. Chronic obstructive pulmonary disease (COPD) involves
      persistent inflammation, but the role of MDSC has not been explored. Here,
      proportions of MDSC (CD14(-)HLA-DR(-)CD33(+)CD11b(+) cells) were quantified in
      peripheral blood mononuclear cells (PBMC) isolated from patients with 'stable'
      COPD (n = 12), smokers with no evidence of COPD (n = 11) and healthy non-smokers
      (n = 11). The proportions of MDSC were similar in all groups. MDSC function was
      assessed by comparing T-cell and cytokine responses of whole and MDSC-depleted
      PBMC stimulated with Staphylococcus enterotoxin-B (SEB). Depletion of MDSC did
      not enhance CD4(+) or CD8(+) T-cell activation and proliferation, or alter
      IFNgamma and IL-17 production in response to SEB. However production of TGFbeta
      decreased after depletion of MDSC, so MDSC may be a source of this cytokine. In
      conclusion, COPD was not associated with perturbations in the proportion or
      function of MDSC in peripheral blood.

PMID- 24090683
TI  - Meta-analysis of differentially expressed genes in primary Sjogren's syndrome by
      using microarray.
AB  - INTRODUCTION: The purpose of this study was to identify differentially expressed
      (DE) genes and biological processes associated with changes in gene expression in
      primary Sjogren's syndrome (pSS). METHODS: We performed a meta-analysis using the
      INMEX program (integrative meta-analysis of expression data) of publicly
      available microarray GEO datasets of pSS. We performed Gene Ontology (GO)
      enrichment analyses and pathway analysis using Kyoto Encyclopedia of Genes and
      Genomes (KEGG). RESULTS: Three GEO datasets including 37 cases and 33 controls
      were available for the meta-analysis. We identified 179 genes across the studies
      which were consistently DE in pSS (146 up-regulated and 33 down-regulated). The
      up-regulated gene with the largest effect size (ES) (ES = -2.4228) was SELL
      (selectin L), whose product is required for the binding and subsequent rolling of
      leucocytes on endothelial cells to facilitate their migration into secondary
      lymphoid organs and inflammation sites. The most significant enrichment was in
      the immune response GO category (P = 2.52 * 10(-25)). The most significant
      pathway in our KEGG analysis was Epstein-Barr virus infection (P = 9.91 * 10(
      06)). CONCLUSIONS: Our meta-analysis demonstrated genes that were consistently DE
      and biological pathways associated with gene expression changes with pSS.

PMID- 24090684
TI  - The economic burden of disease-related undernutrition in selected chronic
      diseases.
AB  - BACKGROUND & AIMS: Undernutrition is a common and aggravating problem in people
      suffering from various chronic diseases as well as a source of material costs.
      The aim of this study was to investigate the prevalence of disease-related
      undernutrition among adults in Croatia in the year 2012, as well as the cost of
      undernutrition associated with tumour cachexia, chronic pancreatitis,
      inflammatory bowel disease, hepatic encephalopathy, chronic obstructive pulmonary
      disease, chronic renal insufficiency requiring dialysis, cerebrovascular insult,
      pressure ulcers, and femoral fractures in the elderly. METHODS: A cost-of-illness
      analysis was conducted, including direct costs only. The study employed the
      dominant cost-of-illness method, which restricts the summation of medical
      expenditure to the disease of interest. The bottom-up, prevalence-based approach
      was used. The budget holder perspective was employed, and data sources include
      the list of reimbursed drugs, clinical opinions, and literature. RESULTS: The
      prevalence of disease-related undernutrition in people over the age of 20 in
      Croatia in the year 2012 was estimated to be 33.7/1000. The total cost of adult
      malnutrition for selected diagnoses was 97.35 million EUR, accounting for 3.38%
      of the total Croatian national health care budget. The largest share was used for
      medications (43%), followed by 34% for hospitalizations, 13% for community health
      nursing, while parenteral and enteral nutrition contributed with 6% and 1%
      respectively. The average cost per patient was estimated at 1640.48 EUR.
      CONCLUSIONS: The cost of malnutrition for the selected diagnoses in Croatia was
      substantial. These health costs will increase due to population ageing, which
      calls for undernutrition screening in people at risk as well as for effective
      approaches in nutrition supplementation.

PMID- 24090685
TI  - "Fast proteins" with a unique essential amino acid content as an optimal
      nutrition in the elderly: growing evidence.
AB  - BACKGROUND & AIMS: Adequate protein intake is crucial to maintain body protein
      content in elderly subjects, but quality of dietary proteins should be also
      considered since amino acid composition and rate of protein digestion modulate
      amino acid availability. This study investigates whether the efficacy of optimal
      protein intake levels for protein retention in the elderly is influenced by
      protein quality. METHODS: We investigated the effect of a 10-day adequate-protein
      (AP) or high-protein (HP) diet together with the protein source as caseins (CAS)
      or soluble milk proteins (PRO) on whole-body (WB) protein synthesis (PS) and
      protein breakdown (PB) in 4 groups of healthy elderly men (mean +/- SEM: 71.8 +/-
      24.4 yr). The study consisted of two periods of 4 h each: a post-absorptive
      period and a postprandial period. The fed state was defined by consumption every
      20 min and for 4 h, of either 15 g or 30 g of PRO or CAS. Steady-state WB and
      splanchnic leucine kinetics were measured using a continuous infusion of L-[1
      13C]leucine in the postabsorptive state and L-[1-13C]leucine infusion plus oral L
      [5,5,5-2H3]leucine in the postprandial state. RESULTS: WB PS was stimulated by
      feeding only with HP diets, whereas WB PB corrected for splanchnic extraction
      showed a similar pattern of post-feeding decrease in all groups. Consequently,
      net leucine balance was greater in the postprandial state after HP meals than
      after AP meals, with PRO meals leading to a better postprandial leucine balance
      (3.63 +/- 0.16 MUmol kg FFM(-1) min(-1)vs. 2.77 +/- 0.21 MUmol kg FFM(-1) min(-1)
      for PRO HP and CAS HP, respectively; P = 0.005). CONCLUSION: Postprandial protein
      retention was better improved in elderly men by an increase in protein intake
      when the protein supplementation was provided as fast-digesting proteins that
      induce high leucine availability.

PMID- 24090686
TI  - Two new species of polystomes (Monogenea: Polystomatidae) from the anuran host
      Guibemantis liber.
AB  - Madapolystoma ramilijaonae n. sp. and Madapolystoma cryptica n. sp. (Monogenea,
      Polystomatidae) are described from the urinary bladder of disjunct populations of
      the Madagascar shrub frog Guibemantis liber. Although only minor morphological
      characters distinguish the new species from the single nominal species of the
      genus, i.e. Madapolystoma biritika, their strong and concordant differentiation
      in a mitochondrial and a nuclear gene supplemented by phylogenetic analyses
      indicates that M. ramilijaonae n. sp. and M. cryptica n. sp. should be regarded
      as two distinct species. Because anuran polystomes are known to be host-specific,
      the description of two cryptic species from a single host species points to a
      taxonomic complex situation in G. liber, a widespread frog that is characterized
      by the presence of several deep conspecific lineages and possibly by
      hybridization and admixture with other species of Guibemantis. 

PMID- 24090687
TI  - The GHRH + arginine stimulated pituitary GH secretion in children and adults with
      Prader-Willi syndrome shows age- and BMI-dependent and genotype-related
      differences.
AB  - OBJECTIVE: The quantitative and qualitative aspects of the pituitary response in
      children and adults with Prader-Willi syndrome (PWS) are compared in order to
      verify the possible age-dependent and genotype-related differences in terms of GH
      secretion. DESIGN: 29 young subjects (21 males and 8 females) and 65 adults (24
      males and 41 females) with PWS were studied. All subjects underwent a standard GH
      Releasing Hormone (GHRH 1-29, 1 MUg/kg as i.v. bolus at 0 minutes)+arginine (0.5
      g/kg) test. Peak GH values, standard GH area under the curve (AUC), AUC of the
      instantaneous secretion rate (ISR), and secretion response analysis (i.e. half
      secretion time) were evaluated. A regression analysis was performed to
      investigate which are the patient characteristics that affect the amplitude and
      shape of the GH secretion response. RESULTS: Peak GH values and AUCGH were
      significantly higher in PWS children than in PWS adults, these differences being
      also significant both in PWS DEL15 (only peak GH value) and PWS UPD15. Moreover,
      PWS children showed significantly lower half secretion time than PWS adults, this
      delayed response being present both in PWS DEL15 and PWS UPD15. Significant
      negative correlations between AUCGH and BMISDS were observed in the two groups
      (adults and children), as well as in adults and children DEL15, but not in adults
      and children PWS UPD15. A regression analysis performed on the whole dataset
      showed that for PWS DEL15 the statistically significant variable explaining GH
      responsiveness was BMISDS (p<0.0001), while for UPD15 no statistically
      significant covariate was found. Conversely, when the delay of the secretion
      response was considered, the regression model yielding the best performances was
      the one with only age as a regressor (p<0.001). CONCLUSIONS: The quantitative and
      qualitative analyses of GH responsiveness to GHRH+arginine highlight relevant
      differences between PWS children and PWS adults and genotype-related traits. The
      negative influence of BMISDS on GH secretion reinforces the need for an early
      start of life-long weight management in PWS subjects.

PMID- 24090689
TI  - Laparoscopic colorectal surgery for diverticular disease is not suitable for the
      early part of the learning curve. A retrospective cohort study.
AB  - AIM: We evaluate the challenges of laparoscopic colorectal surgery for
      diverticular disease. METHODS: Retrospective study of elective laparoscopic
      colorectal procedures (LCP) performed 2002-2011. The study compares LCP for
      Diverticular disease (S group) with both LCP for other pathology (C1 group) and
      open procedures for diverticular disease (C2 group). Statistical analysis was
      performed using Fisher's exact test, Student "t" test and Mann Whitney U-test.
      RESULTS: The study included 194 LCP out of which 22 were in S group. Conversion
      rate in S group was 27.3% vs 9.9% in C1 group, p = 0.017. The mean operating time
      was significantly higher in S group (250 min) compared with 196 min in C1 group,
      p = 0.0004. The median length of hospital stay was 6 days in S group and 4 days
      in C group, p = 0.12. Both morbidities and mortality rates were not statistically
      different between the two groups. In the second part of the study we compare LCP
      with OCP performed for diverticular disease. CONCLUSION: LCP for Diverticular
      disease are technically challenging and should be attempted later in the learning
      curve.

PMID- 24090688
TI  - Association between dietary folate intake and serum insulin-like growth factor-1
      levels in healthy old women.
AB  - OBJECTIVE: High serum levels of insulin-like growth factor-1 (IGF-1) seem to
      coincide with higher rates of some types of cancer and the risk of all-cause
      mortality in old people. Eating vegetables seems to reduce IGF-1 levels because
      they are rich in micronutrients such as vitamins. This study investigates the
      possible association between vitamin intake and IGF-1 levels in a representative
      group of healthy elderly women with Mediterranean dietary habits. DESIGN: This
      cross-sectional study included 124 healthy women with a mean age of 71.3 +/- 4.2
      years and a mean body mass index (BMI) of 27.37 +/- 3.48 kg/m(2) attending a mild
      fitness program twice a week at public gyms in Padova. The main parameters
      considered were IGF-1 (measured by chemiluminescence) and diet, assessed on the
      basis of a 3-day record and a questionnaire on the frequency with which they
      usually ate certain foods. RESULTS: The mean IGF-1 level for the sample as a
      whole was 136.2 +/- 38.9 MUg/l, and was significantly lower in women with a
      higher folate intake (p = 0.04). On simple linear analysis, the vitamins found
      associated with serum IGF-1 levels were: folates (r: -0.25; p = 0.003); vitamin E
      (r: -0.21; p = 0.01); vitamin D (r: -0.17; p = 0.03); and riboflavin (r: -0.16;
      p=0.03). After removing the effect of calorie, protein, carbohydrate and fat
      intake, and other known potential confounders (age, BMI, alcohol intake), only
      folate intake correlated with IGF-1 levels (r = -0.17; p = 0.04). CONCLUSION: A
      folate-rich diet could have the effect of lowering circulating IGF-1 levels in
      elderly women.

PMID- 24090690
TI  - Locum doctors: patient safety is more important than the cost.

PMID- 24090691
TI  - Evaluation of chitosan-gelatin films for use as postoperative adhesion barrier in
      rat cecum model.
AB  - BACKGROUND: Postoperative adhesions remain a significant complication of
      abdominal surgery and can result in pain, infertility and potentially lethal
      bowel obstruction. Pharmacotherapy and barrier devices have reduced adhesion
      formation to varying degrees in preclinical studies or clinical trials. MATERIALS
      AND METHODS: In this study, we produced blends between chitosan (Ch) and gelatin
      (G) with various compositions (Ch/G 100/0, 75/25, 50/50, 25/75 w/w) as candidate
      materials for prevention of postoperative abdominal adhesion. For in vivo
      analysis, 30 female rats weighing 200-250 g were divided into 5 groups (One
      control and 4 treatment groups). Under general anesthesia, the anterior surface
      of serous membrane in rat was scraped slightly with sterile gauze until obvious
      congestion and small bleeding drops appeared, then sample films set on the cecum
      in treatment groups and the intestine was put back into the abdominal cavity,
      which were then closed. After 4 weeks, the abdominal cavity was reopened and the
      grades of peritoneal adhesion were studied by macroscopic and pathologic
      assessments. RESULTS: Our results showed Ch1/G3 films had an insignificant
      reduction effect on postoperative adhesion, but surprisingly, the sample with
      more than 25% by weight of chitosan did not have any effect on reducing adhesion
      formation but also increased inflammation near the cecum. CONCLUSION:
      Administration of chitosan-gelatin films with higher than 25% weight of chitosan
      had no effect on reduction of adhesion formation in the rat cecum model.

PMID- 24090692
TI  - Stress contributes to the development of central insulin resistance during aging:
      implications for Alzheimer's disease.
AB  - It is becoming evident that chronic exposure to stress not only might result in
      insulin resistance or cognitive deficits, but may also be considered a risk
      factor for pathologies such as depression or Alzheimer's disease (AD). There is
      great interest in determining the molecular mechanisms underlying interactions
      between stress, aging, memory and Alzheimer's disease (AD). We have used the
      chronic mild stress (CMS) model to study the effects of chronic stress on the
      aging process and the development of central insulin resistance and AD pathology.
      CMS aged mice showed cognitive impairments in the novel object recognition test.
      In addition, CMS aged mice displayed both peripheral insulin resistance, as shown
      by HOMA index, and decreased hippocampal levels of pIRS and downstream
      intracellular signaling (pAKT, pGSK and pERK1/2). Interestingly, there was a
      significant increase in both C99:C83 ratio and BACE1 levels in the hippocampus of
      CMS aged mice. Increased expression of the AD marker pTau was also found in
      stressed aged mice. Increased expression of the stress-activated protein kinase
      JNK was found in CMS aged mice, accompanied by significant decreases in
      glucocorticoid receptor (GR) expression and increases in mineralocorticoid
      receptor (MR) expression. It is suggested that the interaction of stress with
      aging should be considered when studying determinants of the onset and
      progression of AD. 

PMID- 24090693
TI  - Detection and quantification of hepatopancreatic parvovirus in penaeid shrimp by
      real-time PCR assay.
AB  - As one of the major pathogens, hepatopancreatic parvovirus (HPV) can cause severe
      diseases in penaeid shrimp. We developed a TaqMan-based real-time PCR assay for
      the HPV detection in China. A pair of primers (HPVF and HPVR) and a TaqMan probe
      were designed according to the HPV genomic sequence of Chinese isolate (GenBank:
      GU371276). Our data showed that the primers and TaqMan probe were specific for
      HPV, and they exhibited no cross-reaction with infectious hypodermal and
      hematopoietic necrosis virus (IHHNV), white spot syndrome virus (WSSV) and
      specific pathogen free (SPF) shrimp DNA. The assay had a detection limit of four
      plasmid HPV DNA copies per reaction. Furthermore, HPV was detected in 16 of 21
      Fenneropenaeus Chinensis, 3 of 52 Litopenaeus vannamei and 2 of 2 Marsupenaeus
      japonicus penaeid shrimp samples. In addition, HPV was also detected in crabs.
      Therefore, this assay could be successfully used as a sensitive and rapid
      molecular-based diagnostic method to screen HPV-free animals and survey the
      prevalence of HPV in cultured populations of penaeid shrimp in China. 

PMID- 24090694
TI  - Clinically manifest thromboembolic complications of femoral vein catheterization
      for continuous renal replacement therapy.
AB  - PURPOSE: The safety of femoral vein (FV) catheterization for continuous renal
      replacement therapy is uncertain. We sought to determine the incidence of
      clinically manifest venous thromboembolism (VTE) in such patients. METHODS: We
      retrospectively studied patients with femoral high flow catheters (>= 13F)
      (December 2005 to February 2011). Discharge diagnostic codes were independently
      screened for VTE. The incidence of VTE was also independently similarly assessed
      in a control cohort of patients ventilated for more than 2 days (January 2011 to
      December 2011) in the same intensive care unit (ICU). RESULTS: We studied 380
      patients. Their mean age was 61 years, and 59% were male. The mean Acute
      Physiology and Chronic Health Evaluation III score was 84; average duration of
      continuous renal replacement therapy was 74 hours, and 232 patients (61%)
      survived to hospital discharge with an average length of hospital stay of 22
      days. Only 5 patients (1.3%) had clinically manifest VTE after FV
      catheterization. In the control cohort of 514 ICU patients, the incidence of VTE
      was 4.4% (P < .05 compared with FV group). CONCLUSION: The incidence of
      clinically manifest VTE after FV catheterization with high flow catheters is low
      and lower to that seen in general ICU patients.

PMID- 24090695
TI  - Diabetes mellitus and community-acquired bloodstream infections in the critically
      ill.
AB  - INTRODUCTION: Community-acquired bloodstream infections have not been studied
      related to diabetes mellitus in the critically ill. HYPOTHESIS: We hypothesized
      that the diagnosis of diabetes mellitus and poor chronic glycemic control would
      increase the risk of community-acquired bloodstream infections (CA-BSIs) in the
      critically ill. METHODS: We performed an observational cohort study between 1998
      and 2007 in 2 teaching hospitals in Boston, Massachusetts. We studied 2551
      patients 18 years or older, who received critical care within 48 hours of
      admission and had blood cultures obtained within 48 hours of admission. The
      exposure of interest was diabetes mellitus defined by International
      Classification of Diseases, Ninth Revision, Clinical Modification, code 250.xx in
      outpatient or inpatient records. The primary end point was CA-BSI (<48 hours of
      hospital admission). Patients with a single coagulase-negative Staphylococcus
      positive blood culture were not considered to have bloodstream infection.
      Associations between diabetes groups and bloodstream infection were estimated by
      bivariable and multivariable logistic regression models. Subanalyses included
      evaluation of the association between hemoglobin A1c (HbA1c) and bloodstream
      infection, diabetes and risk of sepsis, and the proportion of the association
      between diabetes and CA-BSI that was mediated by acute glycemic control. RESULTS:
      Diabetes is a predictor of CA-BSI. After adjustment for age, sex, race, patient
      type (medical vs surgical), and acute organ failure, the risk of bloodstream
      infection was significantly higher in patients with diabetes (odds ratio [OR],
      1.42; 95% confidence interval [CI], 1.10-1.82; P = .006) relative to patients
      without diabetes. The adjusted risk of bloodstream infection was increased in
      patients with HbA1c of 6.5% or higher (OR, 1.31; 95% CI, 1.04-1.65; P = .02)
      relative to patients with HbA1c less than 6.5%. Furthermore, the adjusted risk of
      sepsis was significantly higher in patients with diabetes (OR, 1.26; 95% CI, 1.04
      1.54; P = .02) relative to patients without diabetes. Maximum glucose did not
      significantly mediate the relationship between diabetes mellitus diagnosis and CA
      BSI. CONCLUSIONS: A diagnosis of diabetes mellitus and HbA1c of 6.5% or higher is
      associated with the risk of CA-BSI in the critically ill.

PMID- 24090696
TI  - Parent Satisfaction Questionnaire with Neonatal Hearing Screening Programs:
      psychometric properties of the Persian version.
AB  - OBJECTIVES: Measuring parent satisfaction with neonatal hearing screening
      programs is one of the most important indicators for assessing the quality and
      effectiveness and a useful instrument to identify service shortfalls. The aims of
      this study were to translate and adapt Parent Satisfaction Questionnaire with
      Neonatal Hearing Screening Programs (PSQ-NHSPs) to Persian language, determine
      the validity and reliability of this translation, and determine the level of
      parent satisfaction with neonatal hearing screening programs in Iran. METHODS:
      Translated Persian version of the original English PSQ-HNSPs was presented to 138
      parents whose children had received hearing screening before discharge from
      hospital. RESULTS: The majority of parents responded strongly agree or agree to
      all dimensions of the questionnaire: overall satisfaction (90.6%), personnel in
      charge of hearing test (60.1%), and appointment activities (58%). Good internal
      consistency reliability (a=0.89) and moderate test-retest reliability (r=0.61) of
      the Persian version of PSQ-NHSPs were indicated. Construct validity was
      demonstrated by a significant positive relationship between overall satisfaction
      and specific dimensions in the questionnaire. CONCLUSION: The Persian version of
      PSQ-NHSPs is a valid and reliable tool to assess the level of parent satisfaction
      with neonatal hearing screening programs.

PMID- 24090697
TI  - Working memory in children with cochlear implants: problems are in storage, not
      processing.
AB  - BACKGROUND: There is growing consensus that hearing loss and consequent
      amplification likely interact with cognitive systems. A phenomenon often examined
      in regards to these potential interactions is working memory, modeled as
      consisting of one component responsible for storage of information and another
      component responsible for processing of that information. Signal degradation
      associated with cochlear implants should selectively inhibit storage without
      affecting processing. This study examined two hypotheses: (1) A single task can
      be used to measure storage and processing in working memory, with recall accuracy
      indexing storage and rate of recall indexing processing; (2) Storage is
      negatively impacted for children with CIs, but not processing. METHOD: Two
      experiments were conducted. Experiment 1 included adults and children, 8 and 6
      years of age, with NH. Procedures tested the prediction that accuracy of recall
      could index storage and rate of recall could index processing. Both measures were
      obtained during a serial-recall task using word lists designed to manipulate
      storage and processing demands independently: non-rhyming nouns were the standard
      condition; rhyming nouns were predicted to diminish storage capacity; and non
      rhyming adjectives were predicted to increase processing load. Experiment 2
      included 98 8-year-olds, 48 with NH and 50 with CIs, in the same serial-recall
      task using the non-rhyming and rhyming nouns. RESULTS: Experiment 1 showed that
      recall accuracy was poorest for the rhyming nouns and rate of recall was slowest
      for the non-rhyming adjectives, demonstrating that storage and processing can be
      indexed separately within a single task. In Experiment 2, children with CIs
      showed less accurate recall of serial order than children with NH, but rate of
      recall did not differ. Recall accuracy and rate of recall were not correlated in
      either experiment, reflecting independence of these mechanisms. CONCLUSIONS: It
      is possible to measure the operations of storage and processing mechanisms in
      working memory in a single task, and only storage is impaired for children with
      CIs. These findings suggest that research and clinical efforts should focus on
      enhancing the saliency of representation for children with CIs. Direct
      instruction of syntax and semantics could facilitate storage in real-world
      working memory tasks.

PMID- 24090698
TI  - Risk factors for colonization with ampicillin and high-level aminoglycoside
      resistant enterococci during hospitalization in the ICU and the impact of prior
      antimicrobial exposure definition: a prospective cohort study.
AB  - The aim of our prospective cohort study was to determine the incidence, genetic
      relatedness and risk factors for colonization with ampicillin and high-level
      aminoglycoside-resistant enterococci (ARHLARE) among patients hospitalized in the
      intensive care unit. During 15-month period, we included 105 patients. The only
      independent risk factor for ARHLARE colonization was days of
      cefotaxime/ceftriaxone therapy [odds ratio (OR): 1.13; 95% confidence interval
      (CI) 1.10-1.27; P  =  0.045]. Patients with higher total use of antibiotics,
      patients on prolonged mechanical ventilation, and patients with urinary tract
      infection (UTI), were also found to be at increased risk to become colonized with
      ARHLARE. Pulsed-field gel electrophoresis suggested multifocal origin of the
      majority of the colonizing strains. Our results show that an increase in total
      antibiotic consumption for 10 defined daily doses (DDD)/patient increased the
      odds of colonization with ARHLARE for 36%. Further efforts to optimize
      antimicrobial use in high risk patients are proposed.

PMID- 24090700
TI  - beta-Lapachone: a naphthoquinone with promising antischistosomal properties in
      mice.
AB  - The activity of beta-lapachone (3,4-dihydro-2,2-dimethyl-2H-naphthol[1,2-b]pyran
      5,6-dione, beta-lap) against different stages of Schistosoma mansoni was
      investigated in mice. Mice infected with 50 cercariae (BH strain) were
      intraperitoneally treated at a dose of 50 mg/kg for 5 consecutive days, starting
      on the 1st, 14th, 28th and 45th days after infection, to evaluate the effect of
      beta-lap on skin schistosomula, lung schistosomula, young worms (before
      oviposition) and adult worms (after oviposition), respectively. All animals were
      euthanized 60 days after infection. beta-Lap significantly reduced (p<0.001) the
      number of worms in 29.78%, 37.2%, 24.2% and 40.22% when administered during the
      phases of skin schistosomula, lung schistosomula, young worms and adult worms,
      respectively. Significant reduction was also achieved in terms of female burden.
      In all groups, there was significant reduction in the number of eggs and
      granulomas in the hepatic tissue. When the intervention was performed during the
      phase of adult worms, beta-lap reduced the size of hepatic granulomas and changed
      the oogram pattern, lowering the percentage of immature eggs and increasing the
      percentage of mature and dead eggs. Our data indicate that beta-lap has moderate
      antischistosomal properties. Its molecule may also be used as a prototype for
      synthesis of new naphthoquinone derivatives with potential schistosomicidal
      properties. Further studies with different formulations containing beta-lap are
      needed to clearly establish the best dose and route of administration and its
      mechanism of action against schistosomes.

PMID- 24090699
TI  - Visualizing S1P-directed cellular egress by intravital imaging.
AB  - Sphingosine-1-phosphate (S1P) is a bioactive lipid that provides cellular signals
      through plasma membrane G protein-coupled receptors. The S1P receptor signaling
      system has a fundamental and widespread function in licensing the exit and
      release of hematopoietically derived cells from various tissues into the
      circulation. Although the outlines of the mechanism have been established through
      genetic and pharmacologic perturbations, the temporal and spatial dynamics of the
      cellular events involved have been unclear. Recently, two-photon intravital
      imaging has been applied to living tissues to visualize the cellular movements
      and interactions that occur during egress processes. Here we discuss how some of
      these recent findings provide a clearer picture regarding S1P receptor signaling
      in modulating cell egress into the circulation. This article is part of a Special
      Issue entitled New Frontiers in Sphingolipid Biology. 

PMID- 24090701
TI  - Computer models versus reality: how well do in silico models currently predict
      the sensitization potential of a substance.
AB  - National legislations for the assessment of the skin sensitization potential of
      chemicals are increasingly based on the globally harmonized system (GHS). In this
      study, experimental data on 55 non-sensitizing and 45 sensitizing chemicals were
      evaluated according to GHS criteria and used to test the performance of computer
      (in silico) models for the prediction of skin sensitization. Statistic models
      (Vega, Case Ultra, TOPKAT), mechanistic models (Toxtree, OECD (Q)SAR toolbox,
      DEREK) or a hybrid model (TIMES-SS) were evaluated. Between three and nine of the
      substances evaluated were found in the individual training sets of various
      models. Mechanism based models performed better than statistical models and gave
      better predictivities depending on the stringency of the domain definition. Best
      performance was achieved by TIMES-SS, with a perfect prediction, whereby only 16%
      of the substances were within its reliability domain. Some models offer modules
      for potency; however predictions did not correlate well with the GHS
      sensitization subcategory derived from the experimental data. In conclusion,
      although mechanistic models can be used to a certain degree under well-defined
      conditions, at the present, the in silico models are not sufficiently accurate
      for broad application to predict skin sensitization potentials. 

PMID- 24090702
TI  - Caring for military families across the deployment cycle.

PMID- 24090703
TI  - Tourniquets: translating military knowledge into civilian care.

PMID- 24090704
TI  - The emerging role of combat nursing: the ultimate emergency nursing challenge.

PMID- 24090705
TI  - Optimal serum phenylalanine for adult patients with phenylketonuria (PKU).

PMID- 24090706
TI  - Fluctuations in phenylalanine concentrations in phenylketonuria: a review of
      possible relationships with outcomes.
AB  - Fluctuations in blood phenylalanine concentrations may be an important
      determinant of intellectual outcome in patients with early and continuously
      treated phenylketonuria (PKU). This review evaluates the studies on phenylalanine
      fluctuations, factors affecting fluctuations, and if stabilizing phenylalanine
      concentrations affects outcomes, particularly neurocognitive outcome. Electronic
      literature searches of Embase and PubMed were performed for English-language
      publications, and the bibliographies of identified publications were also
      searched. In patients with PKU, phenylalanine concentrations are highest in the
      morning. Factors that can affect phenylalanine fluctuations include age, diet,
      timing and dosing of protein substitute and energy intake, dietary adherence,
      phenylalanine hydroxylase genotype, changes in dietary phenylalanine intake and
      protein metabolism, illness, and growth rate. Even distribution of phenylalanine
      free protein substitute intake throughout 24h may reduce blood phenylalanine
      fluctuations. Patients responsive to and treated with 6R-tetrahydrobiopterin seem
      to have less fluctuation in their blood phenylalanine concentrations than
      controls. An increase in blood phenylalanine concentration may result in
      increased brain and cerebrospinal fluid phenylalanine concentrations within
      hours. Although some evidence suggests that stabilization of blood phenylalanine
      concentrations may have benefits in patients with PKU, more studies are needed to
      distinguish the effects of blood phenylalanine fluctuations from those of poor
      metabolic control. 

PMID- 24090707
TI  - Creatine and guanidinoacetate reference values in a French population.
AB  - Creatine and guanidinoacetate are biomarkers of creatine metabolism. Their assays
      in body fluids may be used for detecting patients with primary creatine
      deficiency disorders (PCDD), a class of inherited diseases. Their laboratory
      values in blood and urine may vary with age, requiring that reference normal
      values are given within the age range. Despite the long known role of creatine
      for muscle physiology, muscle signs are not necessarily the major complaint
      expressed by PCDD patients. These disorders drastically affect brain function
      inducing, in patients, intellectual disability, autistic behavior and other
      neurological signs (delays in speech and language, epilepsy, ataxia, dystonia and
      choreoathetosis), being a common feature the drop in brain creatine content. For
      this reason, screening of PCDD patients has been repeatedly carried out in
      populations with neurological signs. This report is aimed at providing reference
      laboratory values and related age ranges found for a large scale population of
      patients with neurological signs (more than 6 thousand patients) previously
      serving as a background population for screening French patients with PCDD. These
      reference laboratory values and age ranges compare rather favorably with
      literature values for healthy populations. Some differences are also observed,
      and female participants are discriminated from male participants as regards to
      urine but not blood values including creatine on creatinine ratio and
      guanidinoacetate on creatinine ratio values. Such gender differences were
      previously observed in healthy populations; they might be explained by literature
      differential effects of testosterone and estrogen in adolescents and adults, and
      by estrogen effects in prepubertal age on SLC6A8 function. Finally, though they
      were acquired on a population with neurological signs, the present data might
      reasonably serve as reference laboratory values in any future medical study
      exploring abnormalities of creatine metabolism and transport. 

PMID- 24090708
TI  - DiaPep277(r) and immune intervention for treatment of type 1 diabetes.
AB  - Type 1 diabetes is a chronic immune-mediated disease resulting in destruction of
      insulin-producing beta-cells. Several studies have been performed aiming to halt
      disease progression after diagnosis; to reduce the increased diabetes risk in
      islet-autoantibody positive subjects; and to prevent the onset of beta-cell
      autoimmunity in subjects genetically at risk but without autoantibodies. Whereas
      secondary prevention trials failed, trials in newly diagnosed patients have shown
      partial success in preserving C-peptide. These studies target T-cells and
      inflammation and make use of antigen-specific immune modulation or stem cell
      approaches. However, thus far no immune-based therapeutic regimen has cured type
      1 diabetes after its clinical onset or has stabilized the decline of C-peptide to
      achieve the status of an approved drug. This review summarizes immune
      intervention trials and the current knowledge of DiaPep277(r) peptide as a form
      of immune intervention in type 1 diabetes. 

PMID- 24090709
TI  - Antimicrobial and immunomodulating activities of hesperidin and ellagic acid
      against diarrheic Aeromonas hydrophila in a murine model.
AB  - AIMS: The present study is designed to evaluate the in vitro and in vivo
      bactericidal and immunomodulating activities of hesperidin (HES) and ellagic acid
      (EA) against Aeromonas hydrophila. A hydrophila, an uncommon human pathogen, can
      cause invasive infections in immunocompromised individuals and common clinical
      presentations in acute gastrointestinal illness, soft-tissue infections and
      sepsis. The antimicrobial activities of medicinal plants against A. hydrophila
      have received only cursory attention. METHODS: We examined the minimum inhibitory
      concentration (MIC) and minimum bactericidal concentration (MBC) values in vitro.
      Moreover, the effects of HES and EA against bacterial colonization were studied
      in vivo. Also, humoral immune response was tested against A. hydrophila-LPS or A.
      hydrophila-ECP antigen preparations and the intestinal histopathological
      alterations were studied. RESULTS: Data revealed that the treatments with HES and
      EA each had antimicrobial activities against A. hydrophila. Both HES and EA
      treatments significantly increased anti-LPS IgM levels and reduced anti-LPS and
      anti-ECP IgA levels to their normal values in comparison to the infected group,
      which recorded significantly elevated levels two week post-infection. In
      conclusion, the present data suggest that HES and EA have antimicrobial and
      immunomodulating activities against murine A. hydrophila infections. SIGNIFICANT:
      These data warrant clinical studies to delineate HES and EA roles in human
      infectious diseases.

PMID- 24090710
TI  - An unexpected Streptococcus pneumoniae strain.
AB  - This clinical driven report describes the unexpected detection of a multidrug
      resistant (MDR) Streptococcus pneumoniae strain. Italy is usually considered a
      country characterized by a low prevalence of MDR S. pneumoniae. We describe the
      occurrence of bacterial meningitis sustained by a MDR S. pneumoniae strain in
      Italy. The first-line treatment was started with ceftriaxone and dexamethasone,
      but after the identification of such a resistant strain a second-line regimen was
      needed. The new regimen was chosen on both susceptibility and pharmacokinetic
      criteria. Linezolid and levofloxacin were started and a dramatic improvement was
      observed. A more sensitive anamnesis revealed some elements known to be
      associated to a MDR S. pneumoniae occurrence (immunesuppression, former
      antibiotic therapy). So this case should pinpoint our attention on risk factors
      of MDR for a careful choice of antibiotic therapy in serious pneumococcal
      infections. 

PMID- 24090711
TI  - Self-perceived met and unmet care needs of frail older adults in primary care.
AB  - In order to provide adequate care for frail older adults in primary care it is
      essential to have insight into their care needs. Our aim was to describe the met
      and unmet care needs as perceived by frail older adults using a multi-dimensional
      needs assessment, and to explore their associations with socio-demographic and
      health-related characteristics. Cross-sectional baseline data were used from the
      Frail older Adults: Care in Transition (ACT) study in the Netherlands, consisting
      of 1137 community dwelling frail older adults aged 65 and above. Patients were
      recruited through 35 primary care practices. Self-perceived care needs were
      assessed using the Camberwell Assessment of Need for the Elderly (CANE). Socio
      demographic characteristics included age, sex, partner status and educational
      level. Health-related characteristics included functional capacity, hospital
      admissions, chronic diseases and the degree of frailty. Frail older adults
      reported on average 4.2 care needs out of 13 CANE topics, of which 0.5 were
      unmet. The physical and environmental domain constituted the highest number of
      needs, but these were mostly met. Unmet needs were mainly found in the
      psychosocial domain. Regression analyses revealed that Activities of Daily Living
      (ADL) limitations and a higher frailty score were the most important determinants
      of both met and unmet care needs. A younger age and a higher educational level
      were associated with the presence of unmet care needs. In conclusion, most frail
      older adults in primary care report to receive sufficient help for their physical
      needs. More attention should be paid to their psychosocial needs. 

PMID- 24090713
TI  - Improving catalytic hydrolysis reaction efficiency of sol-gel-encapsulated
      Candida rugosa lipase with magnetic beta-cyclodextrin nanoparticles.
AB  - A silica-based beta-cyclodextrin was immobilized on magnetic nanoparticles to
      obtain a macrocyclic compound with magnetic property. Then, the beta-cyclodextrin
      grafted magnetic nanoparticles were encapsulated with Candida rugosa lipase in
      sol-gel matrices using alkoxysilane precursors. The catalytic activity of the
      encapsulated lipases was evaluated with model reactions, i.e., the hydrolysis of
      p-nitro-phenylpalmitate (p-NPP) and the enantioselective hydrolysis of rasemic
      Naproxen methyl ester that was studied in an aqueous buffer solution/isooctane
      reaction system. The results indicate that the cyclodextrin-based, encapsulated
      lipase particularly exhibited high conversion and enantioselectivity behavior
      compared to the sol-gel free lipase. It was also observed that excellent
      enantioselectivity (E=399) was obtained for the encapsulated lipase with magnetic
      beta-cyclodextrin that has an ee value of S-Naproxen acid of about 98%. 

PMID- 24090714
TI  - Cytotoxicity assessment of MDA-MB-231 breast cancer cells on screen-printed
      graphene-carbon paste substrate.
AB  - Graphene is a novel carbon-based material widely studied in bio-electrochemical
      fields because of its high electrical conductivity and excellent electrocatalytic
      activity. However, its biological applications have been limited due to the lack
      of understanding of its compatibility with numerous biological entities. In this
      paper, cytoxicities of MDA-MB-231 breast cancer cells (MDA cells) on carbon paste
      (CP) and graphene-carbon paste (GCP) substrates are assessed. GCP was prepared by
      mixing graphene powder into carbon paste with different graphene contents.
      Cytotoxic effect was evaluated from cell viability, cell adhesion, ROS production
      and fluorescence staining studies. Cell viability on GCP substrate was found to
      initially increase as graphene content increases from 0 to 2.5 wt% but then
      decrease as the content increases further. In addition, the viability decreases
      with time for all substrates. Similarly, graphene concentration affected the
      number of adherent cells in the same manner as the cell viability. Likewise,
      reactive oxygen species (ROS) induced by carbon substrate increased with time and
      decreased with small graphene inclusion, confirming that low graphene content led
      to lower cytotoxicity. Moreover, confluence of MDA cells on substrate evaluated
      using Hoechst 33342 fluorescence staining was also found to be enhanced at low
      graphene concentration. Therefore, low-content graphene incorporation can
      effectively improve biocompatibility of carbon-based materials with MDA-MB-231
      breast cancer cells, enabling potential applications such as electrochemical
      electrode for cell study.

PMID- 24090712
TI  - Cerebral gray matter volumes and low-frequency fluctuation of BOLD signals in
      cocaine dependence: duration of use and gender difference.
AB  - BACKGROUND: Magnetic resonance imaging has provided a wealth of information on
      altered brain activations and structures in individuals addicted to cocaine.
      However, few studies have considered the influence of age and alcohol use on
      these changes. METHODS: We examined gray matter volume with voxel based
      morphometry (VBM) and low frequency fluctuation (LFF) of BOLD signals as a
      measure of cerebral activity of 84 cocaine dependent (CD) and 86 healthy control
      (HC) subjects. We performed a covariance analysis to account for the effects of
      age and years of alcohol use. RESULTS: Compared to HC, CD individuals showed
      decreased gray matter (GM) volumes in frontal and temporal cortices,
      middle/posterior cingulate cortex, and the cerebellum, at p<0.05, corrected for
      multiple comparisons. The GM volume of the bilateral superior frontal gyri (SFG)
      and cingulate cortices were negatively correlated with years of cocaine use, with
      women showing a steeper loss in the right SFG in association with duration of
      use. In contrast, the right ventral putamen showed increased GM volume in CD as
      compared to HC individuals. Compared to HC, CD individuals showed increased
      fractional amplitude of LFF (fALFF) in the thalamus, with no significant overlap
      with regions showing GM volume loss. CONCLUSIONS: These results suggested that
      chronic cocaine use is associated with distinct changes in cerebral structure and
      activity that can be captured by GM volume and fALFF of BOLD signals.

PMID- 24090716
TI  - Impaired fear inhibition learning predicts the persistence of symptoms of
      posttraumatic stress disorder (PTSD).
AB  - Recent cross-sectional studies have shown that the inability to suppress fear
      under safe conditions is a key problem in people with posttraumatic stress
      disorder (PTSD). The current longitudinal study examined whether individual
      differences in fear inhibition predict the persistence of PTSD symptoms.
      Approximately 2 months after deployment to Afghanistan, 144 trauma-exposed Dutch
      soldiers were administered a conditional discrimination task (AX+/BX-). In this
      paradigm, A, B, and X are neutral stimuli. X combined with A is paired with a
      shock (AX+ trials); X combined with B is not (BX- trials). Fear inhibition was
      measured (AB trials). Startle electromyogram responses and shock expectancy
      ratings were recorded. PTSD symptoms were measured at 2 months and at 9 months
      after deployment. Results showed that greater startle responses during AB trials
      in individuals who discriminated between danger (AX+) and safety (BX-) during
      conditioning, predicted higher PTSD symptoms at 2 months and 9 months post
      deployment. The predictive effect at 9 months remained significant after
      controlling for critical incidents during previous deployments and PTSD symptoms
      at 2 months. Responses to AX+ or BX- trials, or discrimination learning (AX+
      minus BX-) did not predict PTSD symptoms. It is concluded that impaired fear
      inhibition learning seems to be involved in the persistence of PTSD symptoms. 

PMID- 24090715
TI  - Resting state EEG power and coherence abnormalities in bipolar disorder and
      schizophrenia.
AB  - Resting state electroencephalogram (EEG) abnormalities in schizophrenia and
      bipolar disorder patients suggest alterations in neural oscillatory activity.
      However, few studies directly compare these anomalies between patient groups, and
      none have examined EEG coherence. Therefore, this study investigated whether
      these electrophysiological characteristics differentiate clinical populations
      from one another, and from non-psychiatric controls. To address this question,
      resting EEG power and coherence were assessed in 76 bipolar patients (BP), 132
      schizophrenia patients (SZ), and 136 non-psychiatric controls (NC). We conducted
      separate repeated-measures ANOVAs to examine group differences within seven
      frequency bands across several brain regions. BP showed significantly greater
      power relative to SZ at higher frequencies including Beta and Gamma across all
      regions. In terms of intra-hemispheric coherence, while SZ generally exhibited
      higher coherence at Delta compared to NC and BP, both SZ and BP showed higher
      coherence at Alpha1 and Alpha2. In contrast, BP and HC showed higher coherence
      within hemispheres compared to SZ at Beta 1. In terms of inter-hemispheric
      coherence, SZ displayed higher coherence compared to NC at temporal sites at both
      Alpha1 and Alpha2. Taken together, BP exhibited increased high frequency power
      with few disruptions in neural synchronization. In contrast, SZ generally
      exhibited enhanced synchronization within and across hemispheres. These findings
      suggest that resting EEG can be a sensitive measure for differentiating between
      clinical disorders. 

PMID- 24090717
TI  - Evaluating summarised radionuclide concentration ratio datasets for wildlife.
AB  - Concentration ratios (CR(wo-media)) are used in most radioecological models to
      predict whole-body radionuclide activity concentrations in wildlife from those in
      environmental media. This simplistic approach amalgamates the various factors
      influencing transfer within a single generic value and, as a result, comparisons
      of model predictions with site-specific measurements can vary by orders of
      magnitude. To improve model predictions, the development of 'condition-specific'
      CR(wo-media) values has been proposed (e.g. for a specific habitat). However, the
      underlying datasets for most CR(wo-media) value databases, such as the wildlife
      transfer database (WTD) developed within the IAEA EMRAS II programme, include
      summarised data. This presents challenges for the calculation and subsequent
      statistical evaluation of condition-specific CR(wo-media) values. A further
      complication is the common use of arithmetic summary statistics to summarise data
      in source references, even though CR(wo-media) values generally tend towards a
      lognormal distribution and should, therefore, be summarised using geometric
      statistics. In this paper, we propose a statistically-defensible and robust
      method for reconstructing underlying datasets to calculate condition-specific
      CR(wo-media) values from summarised data and deriving geometric summary
      statistics. This method is applied to terrestrial datasets from the WTD.
      Statistically significant differences in sub-category CR(wo-media) values (e.g.
      mammals categorised by feeding strategy) were identified, which may justify the
      use of these CR(wo-media) values for specific assessment contexts. However,
      biases and limitations within the underlying datasets of the WTD explain some of
      these differences. Given the uncertainty in the summarised CR(wo-media) values,
      we suggest that the CR(wo-media) approach to estimating transfer is used with
      caution above screening-level assessments.

PMID- 24090718
TI  - Expanding the phenotype of IFAP/BRESECK syndrome: a new case with severe
      hypogammaglobulinemia.
AB  - The ichthyosis follicular with atrichia and photophobia syndrome (IFAP) is a rare
      X-linked multiple congenital malformation syndrome. Some male patients have
      additional features including brain anomalies, intellectual disability,
      ectodermal dysplasia, skeletal deformities, ear or eye anomalies and kidney
      dysplasia/hypoplasia (BRESEK syndrome) sometimes associated with Hirschsprung
      disease and cleft palate or cryptorchidism (BRESHECK syndrome). We report a 5
      months-old male patient with the p.R429H mutation in MBTPS2 protein, which has
      been reported to be associated with the most severe phenotype of patients with
      IFAP/BRESHECK syndrome. This patient presented with a severe IFAP/BRESHECK
      phenotype including ichthyosis follicular, atrichia, photophobia, brain
      anomalies, global developmental delay, Hirschsprung disease and kidney
      hypoplasia. Additional features not previously reported in IFAP syndrome, include
      severe hypogammaglobulinemia and congenital rectourethral fistula. 

PMID- 24090719
TI  - Independent association between air pollutants and vitamin D deficiency in young
      children in Isfahan, Iran.
AB  - OBJECTIVES: To determine the association between air pollution and vitamin D
      status in young children living in a sunny region. METHODS: This cross-sectional
      study of 100 children aged 4-10 years in Isfahan was conducted during 2011-2012.
      This industrial city has an arid climate and is the second most air-polluted city
      in Iran. Children were selected by random cluster sampling from various areas
      with different levels of air pollution. The air quality index (AQI) was recorded
      and demographic variables, dietary habits and levels of physical activity were
      determined by validated questionnaires. Serum concentrations of 25-hydroxyvitamin
      D [25(OH)D], calcium, phosphate, alkaline phosphatase and parathyroid hormone
      were measured. The P for trend for median (interquartile range) of variables was
      assessed across the AQI quartiles. The associations between AQI and biochemical
      values were assessed by multiple linear regression after adjustment for age,
      gender, BMI, diet and pattern of physical activity. RESULTS: Ninety-seven
      children (46.4% boys) completed the study. The median (interquartile range, IQR)
      of serum 25(OH) D was 37.4 (22.5, 81.6) nmol/L. Median dietary vitamin D intake
      was 11.7 MUg/day, i.e. 78% of the required daily amount. Vitamin D deficiency and
      insufficiency were detected in 37.9% and 46.3% of children, respectively. Median
      (IQR) exposure to ultraviolet B radiation in the AQI Quartile 4 area was
      significantly lower than in the Quartile 1 area [0.36 (0.35-0.38) watts per
      square metre (W/m(2)) vs 0.41 (0.39-0.44) W/m(2), respectively, P = 0.04].
      Likewise, the corresponding figure for serum 25(OH)D was 35.2 (22.5-45.2) vs 52.7
      (44.9-81.6) nmol/L, respectively, P = 0.04. AQI was inversely associated with
      serum 25(OH)D, which remained significant after adjustment for the above
      mentioned confounding factors (beta = 0.61, P = 0.01). CONCLUSION: The
      independent inverse association of AQI with 25(OH)D explains the high prevalence
      of vitamin D deficiency in children in Isfahan. Dietary intake of vitamin D was
      not sufficiently low to explain the very low level of serum 25(OH)D. In regions
      with plenty of sunlight, air pollution should be considered to be a factor in the
      causation of hypovitaminosis D.

PMID- 24090720
TI  - Autologous fat grafting for the treatment of velopharyngeal insufficiency: state
      of the art.
AB  - BACKGROUND: Autologous fat grafting to the velopharynx has been described for
      treatment of velopharyngeal insufficiency for over a decade. The aim of this
      review was to evaluate outcomes of autologous fat grafting for velopharyngeal
      insufficiency. METHODS: A computerized search was performed across multiple
      databases. Studies involving patients undergoing autologous fat grafting for
      velopharyngeal insufficiency treatment that reported at least one pre- and post
      intervention outcome measure were included. RESULTS: A systematic search revealed
      eleven studies that satisfied inclusion criteria. All were case series or
      noncomparative observational studies. Three reported on isolated posterior
      pharyngeal wall augmentation, while eight involved augmentation of the pharyngeal
      arches, velum and/or posterior pharyngeal wall. In general, selected patients had
      plateaued with regards to speech therapy and had small-to-moderate velopharyngeal
      closure defects. Although most patients had a cleft palate diagnosis, the
      proportion that had previous velopharyngoplasty, or other related diagnoses was
      highly variable. In all but one report outcome measures included perceptual
      speech assessment. Objective measures such as nasalance and fat graft take were
      inconsistently reported. Overall, results of fat grafting for velopharyngeal
      insufficiency were variable and depended on assessment modality. One case of
      obstructive sleep apnea was reported. CONCLUSIONS: Despite potential benefits of
      autologous fat grafting for velopharyngeal insufficiency, questions remain as to
      patient selection, safety, and optimal graft volume and injection sites. This
      review underscores the need for standardized assessment methods and prospective
      comparative studies or randomized controlled trials to compare fat grafting with
      established velopharyngoplasty techniques to better define indications for its
      use.

PMID- 24090721
TI  - Cranial distraction osteogenesis for syndromic craniosynostosis: long-term follow
      up and effect on postoperative cranial growth.
AB  - BACKGROUND: Although cranial distraction osteogenesis (CDO) is beneficial, few
      studies have reported on detailed operative procedures and postoperative cranial
      growth. Herein, we demonstrated the objective effectiveness of CDO in younger
      infants. METHODS: The study included infants who underwent primary cranial
      distraction for craniosynostosis. Infants who had hydrocephalus were excluded and
      those who underwent additional osteotomy surgeries were analysed before the
      subsequent procedures. The infants' computed tomography data were analysed using
      Mimics((r)) software (Materialise, Leuven, Belgium) to calculate the cranial
      volumes and compare them with the Abbott curve for a normal population. We
      defined cranial growth gap as the difference between the subject data and normal
      infant data to demonstrate the perioperative effects on cranial growth. RESULTS:
      CDO was performed in 10 infants. The mean infant age at the time of surgery was
      6.4 months (range, 24--61 months) and the mean duration of postoperative follow
      up was 38.9 months (range, 24--61 months). Five infants with Crouzon syndrome and
      five with Apert's syndrome were included. All infants showed postoperative
      cranial growth, but cranial growth gap showed postoperative declines for a
      certain period, indicating cranial growth suppression immediately following
      expansion. At the last follow-up, all cases were within +/-2 standard deviation
      (SD) compared with the normal population. We derived a formula to predict the CDO
      target volume using the declining cranial growth gap curve. CONCLUSIONS: CDO was
      applicable and suitable for younger infants requiring aggressive cranial
      expansion.

PMID- 24090722
TI  - Free-flap cover of complex defects around the knee using the descending genicular
      artery as the recipient pedicle.
AB  - BACKGROUND: Selection of ideal recipient vessels is one of the most important
      factors determining success in free-flap reconstruction of the lower limb. At the
      knee, the choice of vessels has traditionally been either the common femoral or
      the popliteal vessels and their branches but these are often difficult to use or
      cannot be used. METHODS: A series of 32 free flaps for cover of complex injuries
      of the knee involving the distal femur, the knee joint and the upper tibia were
      reconstructed using the descending genicular branch of the femoral artery in the
      adductor canal and its muscular branches to the vastus medialis as the recipient
      vessels. RESULT: All but one flap survived with no major complications.
      CONCLUSION: The use of the descending genicular artery as the recipient vessel
      for reconstruction with free flaps around the knee has various advantages
      including: (i) it is mostly remote from the zone of trauma, (ii) it is constant
      in location, (iii) the recipient vessels are an excellent size match for end-to
      end anastomosis, (iv) there is no need for changes of position of the patient
      when using most free flaps commonly used for knee reconstruction, (v) it is easy
      to harvest these simultaneously, (vi) secondary exposure of the underlying
      skeleton from all quadrants is unlikely to divide the flap pedicle as it is
      superior and (vii), perhaps most important of all, it obviates the need for
      exploration of the popliteal fossa.

PMID- 24090723
TI  - Surgical outcomes in craniosynostosis reconstruction: the use of prefabricated
      templates in cranial vault remodelling.
AB  - Cranio-orbital reshaping for anterior cranial-vault deformities associated with
      craniosynostosis traditionally relies on the surgeon's subjective estimate of the
      shape and appearance of a normal forehead. Computer-aided design/computer-aided
      manufacture (CAD/CAM) bandeau templates to guide reconstruction were introduced
      in our centre to eliminate this subjectivity and to effect more reproducible
      surgical results. The aim of this study was to compare two groups of patients
      (template, n = 14 vs. no template, n = 23) to measure surgical outcomes. The
      virtual, computational version of the template was used as an outcome assessment
      tool. It was used to calculate an intervening area under the curve (AUC) between
      the normative template and the patient's reconstructed supra-orbital bar on a
      representative computed tomography (CT) axial section. A comprehensive chart
      review was conducted of patients in both groups to examine the preoperative and
      postoperative variables. Based on the analysis performed on the immediate
      postoperative CT scans, in the template group - as compared to the control, no
      template group - the use of the bandeau template led to a greater reduction in
      AUC (74% vs. 56%, p = 0.016), indicating a better conformity between the
      reconstructed supra-orbital bar and the ideal, normal bandeau shape. The duration
      of operation was significantly reduced with the use of the template (212 vs. 258
      min, p < 0.001). The application of prefabricated templates in cranio-orbital
      reshaping is highly useful for accurate preoperative planning; reproducible and
      efficient intra-operative correction of dysmorphology; and objective surgical
      outcomes assessment.

PMID- 24090724
TI  - Zonal perfusion patterns in pedicled free-style perforator flaps.
AB  - INTRODUCTION: Local perforator flaps have become a standard procedure in
      reconstructive surgery. They allow the transfer of large tissue units with
      minimal donor-site morbidity. However, clinical studies on flap perfusion changes
      over time are lacking. The aim of this study was to investigate the perfusion of
      free-style single perforator flaps with an eccentrically located main perforator
      by combined laser Doppler spectrophotometry. PATIENTS AND METHODS: Ten patients
      (six male, four female, 29-71 years) were included in this prospective clinical
      study. All flaps were based on one perforator. Flaps were harvested from the
      trunk (n = 6) or the proximal upper or lower extremity (n = 4). Flap perfusion
      was assessed using a combined laser Doppler spectrophotometry (CLDS) device (O2C,
      Oxygen to See, LEA Medizintechnik, Giessen, Germany) at days 0, 1, 7 and 14 in
      different zones. RESULTS: Flap dimensions were 18.6 +/- 4.7 * 7.2 +/- 1.6 cm. Two
      flaps developed minor tip necroses (<10%), eight flaps survived completely. CLDS
      proved to be very sensitive for the detection of regional perfusion problems. A
      considerable perfusion gradient was observed at days 0 and 1. Here, reduced blood
      flow and post-capillary oxygen saturations were found at the tip when compared to
      the region above main perforator (RAMP). Blood flow remained stable proximally
      while it improved significantly from day 1 to 14 at the tip region. CONCLUSION:
      CLDS is an effective method for objective evaluation of flap perfusion. Although
      distal flap perfusion is diminished initially, the majority of perforator flaps
      with eccentrically located perforators survive completely. Obviously, flap
      perfusion improved between days 1 and 14. This clinical finding might be
      explained by reorganisation of the vascular system with opening of so-called
      connecting or choke vessels. This knowledge might influence decision making in
      perforator flap surgery.

PMID- 24090725
TI  - Low-cost, high-definition video documentation of corrective cleft surgeries using
      a fixed laparoscope.

PMID- 24090726
TI  - Dual pathology affecting the proximal median nerve is interrelated.

PMID- 24090727
TI  - Liposuction for lower limb lipodystrophy in congenital analbuminaemia: a case
      report.
AB  - Congenital analbuminaemia is a very rare autosomal dominant disorder in which
      patients have no serum albumin and markedly low serum total protein
      concentration. Clinically patients present with mild oedema, hypotension, fatigue
      and lipodystrophy often with abnormal body habitus. With only around 50 reported
      cases in the literature worldwide, management of the resulting lipodystrophy
      remains unclear. A 42-year-old male who was diagnosed with congenital
      analbuminaemia presented with bilateral lower limb lipodystrophy
      disproportionately affecting his thighs. This was associated with concerns over
      appearance, difficulties with mobility and finding clothing. He successfully
      underwent bilateral lower leg liposuction and has had no recurrence of his
      symptoms after 12 months. We have demonstrated that liposuction along with
      controlled compression therapy is a safe and effective treatment for managing
      lipodystrophy secondary to congenital analbuminaemia. Although rare, clinicians
      need to be aware that liposuction is a successful treatment modality, which
      should be made available to this select group of patients. 

PMID- 24090728
TI  - Risk factors for intraprocedural and clinically significant delayed bleeding
      after wide-field endoscopic mucosal resection of large colonic lesions.
AB  - BACKGROUND & AIMS: Wide-field endoscopic mucosal resection (WF-EMR) of large
      sessile colonic polyps is a safe and cost-effective outpatient treatment.
      Bleeding is the main complication. Few studies have examined risk factors for
      bleeding during the procedure (intraprocedural bleeding [IPB]) or after it
      (clinically significant post-endoscopic bleeding [CSPEB]). We investigated
      factors associated with IPB and CSPEB in a large prospective study. METHODS: We
      analyzed data from WF-EMRs of sessile colorectal polyps >= 20 mm in size (mean
      size, 35.5 mm), which were performed on 1172 patients (mean age, 67.8 years) from
      June 2008-March 2013 at 7 tertiary hospitals as part of the Australian Colonic
      Endoscopic Resection Study. Data were collected on characteristics of patients
      and lesions, along with outcomes of procedures and clinical and histologic
      analyses. Independent predictors of IPB and CSPEB were identified by multiple
      logistic regression analysis. RESULTS: Of the patients studied, 133 (11.3%) had
      IPB. Independent predictors included increasing lesion size (odds ratio, 1.24/10
      mm; P < .001), Paris endoscopic classification of 0-IIa + Is (odds ratio, 2.12; P
      = .004), tubulovillous or villous histology (odds ratio, 1.84; P = .007), and
      study institutions that performed the procedure on fewer than 75 patients (odds
      ratio, 3.78; P < .001). All IPB was successfully controlled endoscopically. IPB
      prolonged procedures and was associated with early recurrence (relative risk,
      1.68; P = .011). Seventy-three patients (6.2%) had CSPEB. On multivariable
      analysis, CSPEB was associated with proximal colon location (odds ratio, 3.72; P
      < .001), use of an electrosurgical current not controlled by a microprocessor
      (odds ratio, 2.03; P = .038), and IPB (odds ratio, 2.16; P = .016). Lesion size
      and comorbidities did not predict CSPEB. CONCLUSIONS: In a prospective study of
      patients undergoing WF-EMR of large sessile colonic polyps, IPB is associated
      with larger lesions, lesion histology, and Paris endoscopic classification of
      type 0-IIa + Is. IPB prolongs the duration of the procedure, is a marker for
      recurrence, and is associated with CSPEB. CSPEB occurs most frequently in the
      proximal colon and less when current is controlled by a microprocessor.

PMID- 24090730
TI  - Acute pancreatitis: too many classifications-what is a clinician or researcher to
      do?

PMID- 24090729
TI  - Evidence and recommendations for imaging liver fat in children, based on
      systematic review.
AB  - BACKGROUND & AIMS: Fatty liver is a common problem in children and increases
      their risk for cirrhosis, diabetes, and cardiovascular disease. Liver biopsy is
      the clinical standard for diagnosing and grading fatty liver. However,
      noninvasive imaging modalities are needed to assess liver fat in children. We
      performed a systematic review of studies that evaluated imaging liver fat in
      children. METHODS: We searched PubMed for original research articles in peer
      reviewed journals from January 1, 1982, through December 31, 2012, using the key
      words "imaging liver fat." Studies included those in English, and those performed
      in children from birth to 18 years of age. To be eligible for inclusion, studies
      were required to measure hepatic steatosis via an imaging modality and a
      quantitative comparator as the reference standard. RESULTS: We analyzed 9 studies
      comprising 610 children; 4 studies assessed ultrasonography and 5 studies
      assessed magnetic resonance imaging (MRI). Ultrasonography was used in the
      diagnosis of fatty liver with positive predictive values of 47% to 62%. There was
      not a consistent relationship between ultrasound steatosis score and the
      reference measurement of hepatic steatosis. Liver fat as measurements by MRI or
      by spectroscopy varied with the methodologies used. Liver fat measurements by MRI
      correlated with results from histologic analyses, but sample size did not allow
      for an assessment of diagnostic accuracy. CONCLUSIONS: Available evidence does
      not support the use of ultrasonography for the diagnosis or grading of fatty
      liver in children. Although MRI is a promising approach, the data are
      insufficient to make evidence-based recommendations regarding its use in children
      for the assessment of hepatic steatosis.

PMID- 24090731
TI  - Transfusion-induced bone marrow transplant rejection due to minor
      histocompatibility antigens.
AB  - Traditionally, alloimmunization to transfused blood products has focused
      exclusively on recipient antibodies recognizing donor alloantigens present on the
      cell surface. Accordingly, the immunologic sequelae of alloimmunization have been
      antibody mediated effects (ie, hemolytic transfusion reactions, platelet
      refractoriness, anti-HLA and anti-HNA effects, etc). However, in addition to the
      above sequelae, there is also a correlation between the number of antecedent
      transfusions in humans and the rate of bone marrow transplant (BMT) rejection
      under reduced intensity conditioning with HLA-matched or HLA-identical marrow.
      Bone marrow transplant of this nature is the only existing cure for a series of
      nonmalignant hematologic diseases (eg, sickle cell disease, thalassemias, etc);
      however, rejection remains a clinical problem. It has been hypothesized that
      transfusion induces subsequent BMT rejection through immunization. Studies in
      animal models have observed the same effect and have demonstrated that
      transfusion-induced BMT rejection can occur in response to alloimmunization.
      However, unlike traditional antibody responses, sensitization in this case
      results in cellular immune effects, involving populations such as T cell or
      natural killer cells. In this case, rejection occurs in the absence of
      alloantibodies and would not be detected by existing immune-hematologic methods.
      We review human and animal studies in light of the hypothesis that, for distinct
      clinical populations, enhanced rejection of BMT may be an unappreciated adverse
      consequence of transfusion, which current blood bank methodologies are unable to
      detect. 

PMID- 24090732
TI  - Use of the pentagastrin dog model to explore the food effects on formulations in
      early drug development.
AB  - The ability to extrapolate dosage performance from in vitro to in vivo situations
      has an important role in early drug development. In parallel, the Beagle dog has
      come to represent a useful animal model for extrapolation to humans especially
      when drugs formulated for humans are to be tested. In this article, the
      pentagastrin-induced Beagle dog model was validated internally to show that in
      the colony the dogs were generally responsive to known doses of pentagastrin that
      produces effects similar to gastrin in the stomach, i.e., increasing gastric acid
      production and lowering gastric pH. The effect was observed with a short time
      course, maximum pH lowering was observed between 0.5 and 1h with return to
      baseline at 2-4h. The dog stomach pH is a better representative of the human
      fasted stomach with this pretreatment. The ultimate goal was to use these animals
      in a food effect studies to predict the behavior of formulations in humans. The
      results for 4 compounds were provided in the dog and a clear relationship between
      the effect of food in the dog and the effect of food in humans was observed.
      While the directionality (positive or negative) of the effect could be adequately
      predicted, the extent of the effect could not be predicted for all the tested
      formulations of the 4 compounds. The data will be used to generate a database of
      known compounds from which a correlation can be drawn to make future predictions
      using the pentagastrin dog model. 

PMID- 24090733
TI  - Binary classification of chalcone derivatives with LDA or KNN based on their
      antileishmanial activity and molecular descriptors selected using the Successive
      Projections Algorithm feature-selection technique.
AB  - Chalcones are naturally occurring aromatic ketones, which consist of an alpha-,
      beta-unsaturated carbonyl system joining two aryl rings. These compounds are
      reported to exhibit several pharmacological activities, including antiparasitic,
      antibacterial, antifungal, anticancer, immunomodulatory, nitric oxide inhibition
      and anti-inflammatory effects. In the present work, a Quantitative Structure
      Activity Relationship (QSAR) study is carried out to classify chalcone
      derivatives with respect to their antileishmanial activity (active/inactive) on
      the basis of molecular descriptors. For this purpose, two techniques to select
      descriptors are employed, the Successive Projections Algorithm (SPA) and the
      Genetic Algorithm (GA). The selected descriptors are initially employed to build
      Linear Discriminant Analysis (LDA) models. An additional investigation is then
      carried out to determine whether the results can be improved by using a non
      parametric classification technique (One Nearest Neighbour, 1NN). In a case study
      involving 100 chalcone derivatives, the 1NN models were found to provide better
      rates of correct classification than LDA, both in the training and test sets. The
      best result was achieved by a SPA-1NN model with six molecular descriptors, which
      provided correct classification rates of 97% and 84% for the training and test
      sets, respectively. 

PMID- 24090734
TI  - T-2 toxin is hydroxylated by chicken CYP3A37.
AB  - T-2 toxin (T-2) is an acute toxic trichothecene mycotoxin produced mainly by
      Fusarium species, detected in many crops including oats, wheat and barley, in
      animal feed and food. It is important to know the metabolic pathway and kinetics
      of T-2 in food animals given that T-2 can cause serious adverse effects on human
      health. In this study, we investigated the metabolic capacity of chicken CYP3A37
      in the metabolism of T-2 using reconstituted bacteria produced enzymes. Our
      results showed that chicken CYP3A37 is able to convert T-2 to 3'-OH T-2 with an
      apparent Km of 15.29 MUM, and T-2 hydroxylation activity of CYP3A37 is strongly
      inhibited by ketoconazole (IC50=0.11 MUM). We also observed that chicken CYP3A37
      can catalyze erythromycin N-demethylation, another CYP3A-specific activity. These
      findings imply that chicken CYP3A37 may have a broad substrate spectrum, similar
      to its human homologue CYP3A4.

PMID- 24090735
TI  - Aflatoxin G1-induced oxidative stress causes DNA damage and triggers apoptosis
      through MAPK signaling pathway in A549 cells.
AB  - Our previous studies showed that Aflatoxin G1 (AFG1) could induce lung
      adenocarcinoma, and that the cancer cells originated from alveolar type II cells
      (AT-II cells). Recently, we found AFG1 induced structural impairment in rat AT-II
      cells, which may account for an early event in lung tumorigenesis. However, the
      mechanism of AFG1-induced AT-II cell damage remains unclear. DNA damage and
      apoptosis induced by oxidative stress are well accepted causes of cell damage.
      Thus, we explore whether AFG1 activates the reactive oxygen species
      (ROS)/MAPK/apoptosis pathway to cause cell damage in human AT-II cells like the
      cell line (A549). We found AFG1 induced oxidative stress by increasing ROS
      generation and caused DNA double-strand breaks (DSBs) by up-regulating gammaH2AX
      expression. AFG1 also triggered apoptosis in A549 cells by regulating Fas/FasL,
      caspase-8, Bax, Bcl-2, and activating caspase-3. Pre-treatment with antioxidant n
      acetyl-l-cysteine (NAC) reduced ROS generation and DNA DSBs, inhibited apoptosis,
      and increased cell viability in AFG1-treated cells. Furthermore, we found AFG1
      activated ROS-mediated JNK and p38 pathways to induce cell apoptosis in A549
      cells. In conclusion, our results indicate that AFG1 induces oxidative DNA damage
      and triggers apoptosis through ROS-mediated JNK and p38 signaling pathways in
      A549 cells, which may contribute to AFG1-induced AT-II cell damage. 

PMID- 24090736
TI  - Numerical modeling analysis of VOC removal processes in different aerobic
      vertical flow systems for groundwater remediation.
AB  - Vertical flow systems filled with porous medium have been shown to efficiently
      remove volatile organic contaminants (VOCs) from contaminated groundwater. To
      apply this semi-natural remediation strategy it is however necessary to
      distinguish between removal due to biodegradation and due to volatile losses to
      the atmosphere. Especially for (potentially) toxic VOCs, the latter needs to be
      minimized to limit atmospheric emissions. In this study, numerical simulation was
      used to investigate quantitatively the removal of volatile organic compounds in
      two pilot-scale water treatment systems: an unplanted vertical flow filter and a
      planted one, which could also be called a vertical flow constructed wetland, both
      used for the treatment of contaminated groundwater. These systems were
      intermittently loaded with contaminated water containing benzene and MTBE as main
      VOCs. The highly dynamic but permanently unsaturated conditions in the porous
      medium facilitated aerobic biodegradation but could lead to volatile emissions of
      the contaminants. Experimental data from porous material analyses, flow rate
      measurements, solute tracer and gas tracer test, as well as contaminant
      concentration measurements at the boundaries of the systems were used to
      constrain a numerical reactive transport modeling approach. Numerical simulations
      considered unsaturated water flow, transport of species in the aqueous and the
      gas phase as well as aerobic degradation processes, which made it possible to
      quantify the rates of biodegradation and volatile emissions and calculating their
      contribution to total contaminant removal. A range of degradation rates was
      determined using experimental results of both systems under two operation modes
      and validated by field data obtained at different operation modes applied to the
      filters. For both filters, simulations and experimental data point to high
      biodegradation rates, if the flow filters have had time to build up their removal
      capacity. For this case volatile emissions are negligible and total removal can
      be attributed to biodegradation, only. The simulation study thus supports the use
      of both of these vertical flow systems for the treatment of groundwater
      contaminated with VOCs and the use of reactive transport modeling for the
      assessment of VOCs removal and operation modes in these high performance
      treatment systems. 

PMID- 24090737
TI  - Modeling phosphate transport and removal in a compact bed filled with a mineral
      based sorbent for domestic wastewater treatment.
AB  - Phosphorus filter units containing mineral-based sorbents with a high phosphate
      (PO4) binding capacity have been shown to be appropriate for removing PO4 in the
      treatment of domestic wastewater in on-site facilities. However, a better
      understanding of their PO4 removal mechanisms, and reactions that could lead to
      the formation of PO4 compounds, is required to evaluate the potential utility of
      candidate sorbents. Models based on data obtained from laboratory-scale
      experiments with columns of selected materials can be valuable for acquiring such
      understanding. Thus, in this study the transport and removal of PO4 in
      experiments with a laboratory-scale column filled with a commercial silicate
      based sorbent were modeled, using the hydro-geochemical transport code PHREEQC.
      The resulting models, that incorporated the dissolution of calcite, kinetic
      constrains for the dissolution of calcium oxide (CaO) and wollastonite (CaSiO3),
      and the precipitation of amorphous tricalcium phosphate, Ca3(PO4)2, successfully
      simulated the removal of PO4 observed in the experiments. 

PMID- 24090738
TI  - [The voice of the patient and the health professional when volunteering
      information to improve health care results].

PMID- 24090739
TI  - Gaucher disease: a diagnostic challenge for internists.
AB  - Gaucher disease (GD), the most common inherited lysosomal storage disorder, is a
      multiorgan disease due to an autosomal recessive defect of the gene encoding
      glucocerebrosidase enzyme, responsible for the accumulation of glucosylceramide
      (glucocerebroside) into reticuloendothelial cells, particularly in the liver,
      spleen and bone marrow. GD is a clinically heterogeneous disorder and it is
      conventionally classified in type 1 (non-neuronopathic disease), types 2 and 3
      (acute and chronic neuronopathic disease, respectively). Features of clinical
      presentation and organ involvement as well as age, at presentation are highly
      variable among affected patients. Splenomegaly and/or thrombocytopenia are the
      most common presenting features either as incidental findings during routine
      blood count or physical examination. Other possible clinical manifestations can
      be hepatomegaly with abnormal liver function tests, bone pain often associated
      with skeletal complications (pathological fractures, avascular necrosis,
      osteopenia), pulmonary hypertension and, in neuronopathic forms, neurological
      manifestations (dysfunction of eye motility, mild mental retardation, behavioural
      difficulties, choreoathetosis and cramp attacks). For all these reasons GD
      diagnosis is often a real challenge for internists. In the presence of clinical
      suspicion of GD, the diagnosis has to be confirmed measuring the
      betaglucocerebrosidase activity in the peripheral leukocytes and by molecular
      analysis. Each patient needs an accurate initial multisystemic assessment,
      staging the damage of all the possible organs involved, and the burden of the
      disease, followed by regular followup. The correct and early diagnosis permits to
      treat patients properly, avoiding the complications of the disease. 

PMID- 24090740
TI  - Maternal depression, anxiety and stress during pregnancy and child outcome; what
      needs to be done.
AB  - Care for the emotional state of pregnant women remains a neglected aspect of
      obstetric medicine. Many prospective studies have shown that, if a mother is
      depressed, anxious, or stressed while pregnant, this increases the risk for her
      child having a wide range of adverse outcomes, including emotional problems,
      symptoms of attention deficit hyperactivity disorder, or impaired cognitive
      development. Although genetics and postnatal care clearly affect these outcomes,
      evidence for an additional prenatal causal component is substantial. Prenatal
      anxiety or depression may contribute 10-15% of the attributable load for
      emotional and behavioural outcomes. The Nurse Family Partnership remains the only
      intervention that starts in pregnancy and has been shown to have long-term
      benefits for the behaviour of the child. Several other interventions, however,
      are likely to be helpful. Depression, anxiety, and stress during pregnancy are
      frequently undetected by health professionals, and untreated. Programmes to help
      with this should eventually improve child outcome. 

PMID- 24090741
TI  - Delivery of macromolecules across oral mucosa from polymeric hydrogels is
      enhanced by electrophoresis (iontophoresis).
AB  - OBJECTIVE: To develop polymeric hydrogel delivery systems for iontophorseis
      transfer of large molecules across buccal (porcine) mucosa. METHODS: Three
      hydrogels (PVA, HPMC and PVA/HPMC) were prepared as stable gels (7 mm
      diameter/1.5 mm thick). Quantitative (8 and 36 h) assessment of porcine buccal
      mucosa and the three hydrogel delivery systems, using a diffusion cell in vitro
      model, was carried out by UV/vis spectroscopy with three model agents (3 and 10
      kDa dextrans and 12 kDa parvalbumin). Passive and iontophoresis parameters were
      obtained. Experimental and theoretical data were compared. RESULTS: Iontophoresis
      (30 min, 1-8 h) significantly enhanced the delivery of all model agents across
      four single systems (hydrogels and buccal mucosa) and three sandwich systems
      (hydrogels on top of buccal mucosa), as confirmed by time lag factor/enhancement
      ratio (TLF/ER) data. The diffusion coefficients of model agents across buccal
      mucosa (*10(-13) m(2) s(-1)) were ~100 times lower than across single hydrogels
      (2.97-4.80*10(-11) m(2) s(-1)). Solubility values of all agents across hydrogels
      were similar, but lower across buccal mucosa. Permeability of parvalbumin was
      highest across PVA, and for both dextrans across PVA/HPMC. In sandwich systems
      TLFs were similar for all hydrogels, but significantly lower, and ERs
      significantly higher, than tissue alone. Experimental and theoretical TLF data
      were in reasonable agreement. SIGNIFICANCE: The in vitro data show that
      iontophoresis enhanced the delivery of large molecules across polymeric hydrogel
      systems and buccal mucosa. This creates the opportunity of new approaches to drug
      delivery and opens pathways to further research for delivering therapeutic agents
      topically and systemically.

PMID- 24090742
TI  - The impact of hydrofluoric acid etching followed by unfilled resin on the biaxial
      strength of a glass-ceramic.
AB  - OBJECTIVES: To evaluate the null hypotheses that hydrofluoric (HF) acid etching
      time would neither decrease the biaxial flexural strength of a glass-based
      veneering ceramic nor enhance it after silane and unfilled resin (UR)
      applications. METHODS: Disc-shaped IPS e.max ZirPress specimens were allocated
      into 12 groups: G1-control (no-etching), G2-30 s, G3-60 s, G4-90 s, G5-120 s, G6
      60 s+60 s. Groups (G7-G12) were treated in the same fashion as G1-G6, but
      followed by silane and UR applications. Surface morphology and roughness (Ra and
      Rq) of the ceramics were assessed by means of scanning electron microscopy (SEM)
      and profilometry, respectively. Flexural strength was determined by biaxial
      testing. Data were analyzed by two-way ANOVA and the Sidak test (alpha=0.05).
      Weibull statistics were estimated and finite element analysis (FEA) was carried
      out to verify the stress concentration end areas of fracture. RESULTS: The
      interaction (etching time vs. surface treatment) was significant for Ra (p=0.008)
      and Rq (0.0075). Resin-treated groups presented significantly lower Ra and Rq
      than non-treated groups, except for the 60s group (p<0.005). SEM revealed that
      etching affected the ceramic microstructure and that the UR was able to penetrate
      into the irregularities. A significant effect of etching time (p=0.029) on
      flexural strength was seen. G7-G12 presented higher strength than G1-G6
      (p<0.0001). None of experimental groups failed to show 95% confidence intervals
      of sigma0 and m overlapped. FEA showed lower stress concentration after resin
      treatment. SIGNIFICANCE: HF acid etching time did not show a damaging effect on
      the ceramic flexural strength. Moreover, the flexural strength could be enhanced
      after UR treatment.

PMID- 24090743
TI  - Evaluation of the Block Matching deformable registration algorithm in the field
      of head-and-neck adaptive radiotherapy.
AB  - BACKGROUND AND PURPOSE: To compare the accuracy of the Block Matching deformable
      registration (DIR) against rigid image registration (RIR) for head-and-neck multi
      modal images CT to cone-beam CT (CBCT) registration. MATERIAL AND METHODS:
      Planning-CT and weekly CBCT of 10 patients were used for this study. Several
      volumes, including medullary canal (MC), thyroid cartilage (TC), hyoid bone (HB)
      and submandibular gland (SMG) were transposed from CT to CBCT images using either
      DIR or RIR. Transposed volumes were compared with the manual delineation of these
      volumes on every CBCT. The parameters of similarity used for analysis were: Dice
      Similarity Index (DSI), 95%-Hausdorff Distance (95%-HD) and difference of volumes
      (cc). RESULTS: With DIR, the major mean difference of volumes was -1.4 cc for MC,
      revealing limited under-segmentation. DIR limited variability of DSI and 95%-HD.
      It significantly improved DSI for TC and HB and 95%-HD for all structures but
      SMG. With DIR, mean 95%-HD (mm) was 3.01 +/- 0.80, 5.33 +/- 2.51, 4.99 +/- 1.69,
      3.07 +/- 1.31 for MC, TC, HB and SMG, respectively. With RIR, it was 3.92 +/-
      1.86, 6.94 +/- 3.98, 6.44 +/- 3.37 and 3.41 +/- 2.25, respectively. CONCLUSION:
      Block Matching is a valid algorithm for deformable multi-modal CT to CBCT
      registration. Values of 95%-HD are useful for ongoing development of its
      application to the cumulative dose calculation.

PMID- 24090744
TI  - Left and right ventricular effects of anthracycline and trastuzumab chemotherapy:
      a prospective study using novel cardiac imaging and biochemical markers.

PMID- 24090745
TI  - Association of cardiac events with coronary artery disease detected by 64-slice
      or greater coronary CT angiography: a systematic review and meta-analysis.
AB  - BACKGROUND: The value of >=64-slice coronary CT angiography (CCTA) to determine
      odds of cardiac death or non-fatal myocardial infarction (MI) needs further
      clarification. METHODS: We performed a systematic review and meta-analysis using
      publications reporting events/severity of coronary artery disease (CAD) in
      patients with suspected CAD undergoing CCTA. Patients were divided into: no CAD,
      non-obstructive CAD (maximal stenosis <50%), and obstructive CAD (>=50%
      stenosis). Odds ratios with 95% confidence intervals were calculated using a
      fixed or random effects model. Heterogeneity was assessed using the I(2) index.
      RESULTS: We included thirty-two studies comprising 41,960 patients with 363 all
      cause deaths (15.0%), 114 cardiac deaths (4.7%), 342 MI (14.2%), 69 unstable
      angina (2.8%), and 1527 late revascularizations (63.2%) over 1.96 (SD 0.77) years
      of follow-up. Cardiac death or MI occurred in 0.04% without, 1.29% with non
      obstructive, and 6.53% with obstructive CAD. OR for cardiac death or MI was:
      14.92 (95% CI, 6.78 to 32.85) for obstructive CAD, 6.41 (95% CI, 2.44 to 16.84)
      for non-obstructive CAD versus no CAD, and 3.19 (95% CI, 2.29 to 4.45) for non
      obstructive versus obstructive CAD and 6.56 (95% CI, 3.07 to 14.02) for no versus
      any CAD. Similar trends were noted for all-cause mortality and composite major
      adverse cardiovascular events. CONCLUSIONS: Increasing CAD severity detected by
      CCTA is associated with cardiac death or MI, all-cause mortality, and composite
      major adverse cardiovascular events. Absence of CAD is associated with very low
      odds of major adverse events, but non-obstructive disease significantly increases
      odds of cardiac adverse events in this follow-up period.

PMID- 24090746
TI  - Local immune activity in acute coronary syndrome: oxLDL abrogates LPS-tolerance
      in mononuclear cells isolated from culprit lesion.
AB  - BACKGROUND: OxLDL plays a major role in the initiation and progression of
      atherosclerotic lesions even though further factors are needed to promote fibrous
      cap rupture and thrombotic occlusion of the arterial lumen. Pathogens have been
      implicated in this process but it remains unclear how they can cooperate with
      oxLDL in amplifying the destructive inflammatory response. OBJECTIVE: To
      phenotypically analyze culprit coronary inflammatory cells, evaluate their
      responsiveness to endotoxins and ascertain whether oxLDL alters the sensitivity
      of coronary mononuclear cells to bacterial components. METHODS: Mononuclear cells
      isolated from culprit and non-culprit coronary blood samples of patients with ST
      segment elevation myocardial infarction (STEMI) and controls were analyzed for
      cell-specific surface markers and cytokines by flow-cytometry. RESULTS AND
      CONCLUSIONS: CD14+ cells contained elevated levels of TLR4, expressed high CD80,
      and produced huge amounts of inflammatory cytokines in response to LPS. Using a
      well-established model of endotoxin tolerance, we next showed that mononuclear
      cells isolated from control coronary artery, but not from culprit coronary
      artery, were tolerant to LPS, but pre-treatment of such cells with oxLDL
      abrogated LPS tolerance. Flow-cytometry analysis also showed that IL-17A, IL-21
      and IFN-gamma were over-produced by CD4+ and CD56+ cells isolated from the
      culprit coronary artery. All this data indicate that monocytes circulating in the
      culprit coronary artery of patients with STEMI are primed to synthesize high
      levels of inflammatory cytokines and suggest that oxLDL can amplify the
      inflammatory response of such cells to endotoxins.

PMID- 24090747
TI  - The burden of cardiovascular disease amongst psychiatric patients.

PMID- 24090748
TI  - Current practice on the management of acute coronary syndrome in China.

PMID- 24090750
TI  - Recurrence of cardiomyopathy by recurrent pheochromocytoma.

PMID- 24090749
TI  - Real-life effectiveness of statins in the prevention of first acute coronary
      syndrome in France: a prospective observational study.
AB  - BACKGROUND: Evidence on the real effectiveness of statins on acute coronary
      syndrome (ACS) incidence is scarce. We assessed the effectiveness of real-life
      statins on the risk of first non-fatal ACS in a low-cardiovascular-risk country.
      METHODS: Systematic case-control study was conducted in 60 cardiology centres and
      371 general practices from across France. A total of 2238 cases with first ACS
      within 1 month from recruitment and 2238 controls without history of ACS were
      included; controls were matched to ACS cases on sex, age, frequency of visits to
      GPs, date of recruitment and personal history of chronic diseases. Statin
      exposure and risk factors were documented through patient telephone interviews
      and validated against medical records. The index date was the date of ACS for
      cases. Adjusted odds ratios (OR) of first ACS and statin use were estimated by
      multiple conditional logistic regression models controlled for risk factors and
      propensity score for statin exposure. RESULTS: Statin use was associated with
      lower ACS risk, with an adjusted matched OR of 0.67; 95% confidence interval
      (CI): 0.56 to 0.79 for current use (within 2 months) and 0.73; 95% CI: 0.62 to
      0.86 for any use within 24 months [atorvastatin: 0.83 (0.63-1.10), fluvastatin:
      0.75 (0.43-1.30), pravastatin: 0.98 (0.72-1.34), rosuvastatin: 0.49 (0.35-0.68)
      and simvastatin: 0.62 (0.46-0.84)]. The preventive effect of statins on non-fatal
      ACS reached its maximum after one to four years of use. CONCLUSION: A similar
      magnitude of effect for statin use was observed in real life, as compared to
      randomised clinical trials in France.

PMID- 24090751
TI  - The cell wall protein Rhd3/Pga29 is over-expressed in Candida albicans upon
      micafungin treatment.
AB  - Candida albicans cell wall constitutes a sensitive boundary that undergoes
      molecular changes upon environmental injuries. Antimycotics exert an intense
      action on cell wall eliciting both qualitative and quantitative changes of
      resident proteins. The emergence of drug resistance is marked by a modulation of
      cell wall proteomic profile. In this study, we monitored, at the proteome level
      through a two-dimensional gel electrophoresis-based approach, differences of cell
      wall proteins in sensitive and resistant strains of C. albicans, and variations
      occurring upon treatment of these strains with antifungal drugs. We identified
      Rhd3/Pga29, a glycophosphatidylinositol (GPI)-anchored protein, as the main over
      expressed protein in micafungin resistant strain with respect to the sensitive
      control cells. A further increase of Rhd3/Pga29 took place when these resistant
      strains were treated with sub-lethal dose of micafungin. These results were also
      confirmed in other two clinical isolates resistant to caspofungin. Results were
      validated by Western blot analyses and RT-PCR and immunoelectron microscopy
      images confirmed the increase of the Rhd3/Pga29 on the cell wall as well as in
      the cytosolic compartment of the micafungin-treated resistant cells. Rhd3/Pga29
      over-expression upon echinocandin treatment could represent a strategy of C.
      albicans to counteract the toxic action of this drug. A role of this protein has
      also been claimed in the virulence of the fungus, suggesting an involvement of
      Rhd3/Pga29 in the relationship between C. albicans and the host. 

PMID- 24090752
TI  - Performance evaluation of affinity ligands for depletion of abundant plasma
      proteins.
AB  - Human plasma is a commonly used diagnostic fluid in clinical chemistry. In-depth
      plasma proteomic analysis is performed to search for disease biomarkers, however
      the large dynamic range of protein abundance in plasma presents a substantial
      analytical challenge. Removal of abundant plasma proteins using antibody capture
      approaches is a common and attractive means to reduce sample complexity and to
      aid the analysis of lower abundance proteins of interest. A novel class of heavy
      chain camelid-derived affinity ligands produced in Saccharomyces cerevisiae, has
      recently been developed as an alternative to antibody-based depletion methods.
      Here, we evaluate the performance characteristics of these ligands for removal of
      high abundance plasma proteins. Affinity ligands were tested for the removal of
      14 abundant human plasma proteins. The performance characteristics were evaluated
      by gel-electrophoresis and LC-MS/MS of the bound and flow-through fractions. The
      capacity of a 5.6mL column was found to be 125MUL of plasma. Replicate analysis
      demonstrated high column reproducibility and linearity, efficient removal of
      abundant proteins, and enrichment of lower abundance proteins observed after
      depletion. The novel class of affinity ligands provides an attractive alternative
      to traditional antibody-based immunodepletion methods. 

PMID- 24090753
TI  - Rapid immuno-analytical system physically integrated with lens-free CMOS image
      sensor for food-borne pathogens.
AB  - To realize an inexpensive, pocket-sized immunosensor system, a rapid test devise
      based on cross-flow immuno-chromatography was physically combined with a lens
      free CMOS image sensor (CIS), which was then applied to the detection of the food
      borne pathogen, Salmonella typhimurium (S. typhimurium). Two CISs, each retaining
      1.3 mega pixel array, were mounted on a printed circuit board to fabricate a
      disposable sensing module, being connectable with a signal detection system. For
      the bacterial analysis, a cellulose membrane-based immunosensing platform, ELISA
      on-a-chip (EOC), was employed, being integrated with the CIS module, and the
      antigen-antibody reaction sites were aligned with the respective sensor. In such
      sensor construction, the chemiluminescent signals produced from the EOC are
      transferred directly into the sensors and are converted to electric signals on
      the detector. The EOC-CIS integrated sensor was capable of detecting a traceable
      amount of the bacterium (4.22 * 10(3)CFU/mL), nearly comparable to that adopting
      a sophisticated detector such as cooled-charge-coupled device, while having
      greatly reduced dimensions and cost. Upon coupling with immuno-magnetic
      separation, the sensor showed an additional 67-fold enhancement in the detection
      limit. Furthermore, a real sample test was carried out for fish muscles
      inoculated with a sample of 3.3CFU S. typhimurium per 10 g, which was able to be
      detected earlier than 6h after the onset of pre-enrichment by culture.

PMID- 24090754
TI  - An efficient colorimetric biosensor for glucose based on peroxidase-like protein
      Fe3O4 and glucose oxidase nanocomposites.
AB  - An efficient colorimetric biosensor for glucose based on peroxidase-like protein
      Fe3O4 and glucose oxidase nanocomposites is reported in this work. Compared with
      bare MNPs, peroxidase-like casein-MNPs exhibit good catalytic properties,
      stability, dispersibility. Casein incorporated on MNPs notably improves the
      affinity toward both H2O2 and TMB, proved by variation in the determined kinetic
      parameters. As low as 0.2 MUM H2O2 can be detected with a linear range from 0.5
      MUM to 200 MUM H2O2. More importantly, the casein/MNP nanocomposite was further
      used to immobilize GOx and to construct a glucose biosensor for the one-step
      determination of glucose. This method is simple, inexpensive, highly sensitive,
      and selective for glucose detection, with a detection limit of 1.0 MUM over a
      linear range from 3 MUM to 1000 MUM.

PMID- 24090756
TI  - Partnership and consent in MS treatment choice.
AB  - It is not only good medical practice to ensure patients are fully involved in
      their treatment decisions, but it also improves subsequent compliance, and may
      even be cost effective. However, choosing treatments in MS is becoming
      increasingly complex, which means that ensuring patients understand all the
      issues is a challenge and time consuming. Preference sensitive care (which
      applies to current MS immunomodulatory treatments) is particularly vulnerable to
      the individual doctor's opinion and there is an onus on the physician to ensure
      the decision made incorporates the patient's individual values. National patient
      decision making tools are an appropriate solution to this dilemma and may, in the
      future, be a legal requirement in consent to treatment. 

PMID- 24090755
TI  - Glutamate oxidase biosensor based on mixed ceria and titania nanoparticles for
      the detection of glutamate in hypoxic environments.
AB  - We report on the design and development of a glutamate oxidase (GmOx)
      microelectrode for measuring l-glutamic acid (GluA) in oxygen-depleted
      conditions, which is based on the oxygen storage and release capacity of cerium
      oxides. To fabricate the biosensor, a nanocomposite of oxygen-rich ceria and
      titania nanoparticles dispersed within a semi-permeable chitosan membrane was co
      immobilized with the enzyme GmOx on the surface of a Pt microelectrode. The
      oxygen delivery capacity of the ceria nanoparticles embedded in a biocompatible
      chitosan matrix facilitated enzyme stabilization and operation in oxygen free
      conditions. GluA was measured by amperometry at a working potential of 0.6 V vs
      Ag/AgCl. Detection limits of 0.594 uM and 0.493 uM and a sensitivity of 793 pA/uM
      (RSD 3.49%, n=5) and 395 pA/uM (RSD 2.48%, n=5) were recorded in oxygenated and
      deoxygenated conditions, with response times of 2s and 5s, respectively. The
      biosensor had good operational stability and selectivity against common
      interfering substances. Operation of the biosensor was tested in cerebrospinal
      fluid. Preliminary in vivo recording in Sprague-Dawley rats to monitor GluA in
      the cortex during cerebral ischemia and reperfusion demonstrate a potential
      application of the biosensor in hypoxic conditions. This method provides a
      solution to ensure functionality of oxidoreductase enzymes in oxygen-free
      environments.

PMID- 24090757
TI  - Dual task cost of walking is related to fall risk in persons with multiple
      sclerosis.
AB  - Persons with multiple sclerosis (MS) commonly have walking and cognitive
      impairments. While walking with a simultaneous cognitive task, persons with MS
      experience a greater decline in walking performance than healthy controls. This
      change in performance is termed dual task cost or dual task interference and has
      been associated with fall risk in older adults. We examined whether dual task
      cost during walking was related to fall risk in persons with MS. Thirty-three
      ambulatory persons with MS performed walking tasks with and without a concurrent
      cognitive task (dual task condition) as well as underwent a fall risk assessment.
      Dual task cost was operationalized as the percent change in velocity from normal
      walking conditions to dual task walking conditions. Fall risk was quantified
      using the Physiological Profile Assessment. A Spearman correlation analysis
      revealed a significant positive correlation between dual task cost of walking
      velocity and fall risk as well as dual task cost of stride length and fall risk.
      Overall, the findings indicate that dual task cost is associated with fall risk
      and may be an important target for falls prevention strategies. 

PMID- 24090758
TI  - Differentiating cerebellopontine angle meningioma from schwannoma using caloric
      testing and vestibular-evoked myogenic potentials.
AB  - OBJECTIVE: This study utilized audiometry, and caloric, ocular vestibular-evoked
      myogenic potential (oVEMP) and cervical VEMP (cVEMP) tests to differentiate
      between cerebellopontine angle (CPA) meningioma and schwannoma. PATIENTS AND
      METHODS: Eleven CPA meningioma patients with mean tumor size 2.8+/-1.4 cm and
      another 11 CPA schwannoma patients with mean tumor size 2.7+/-1.0 cm were
      enrolled in this study. All patients underwent a battery of audiovestibular
      function tests. RESULTS: The two groups did not differ significantly in terms of
      clinical manifestation. The abnormal percentage of caloric test in the meningioma
      group was 36%, compared to 91% in the schwannoma group, and thus both groups
      differed significantly. However, such difference was not observed between the two
      groups regardless of mean hearing level, oVEMP test and cVEMP test. CONCLUSION:
      Combined caloric with oVEMP test results may help differentiate a CPA tumor.
      Correlation between the caloric and oVEMP test results in a CPA tumor indicates a
      schwannoma nature, while dissociation between the caloric and oVEMP test results
      depicts a meningioma character.

PMID- 24090759
TI  - Novel mutations in ataxia telangiectasia and AOA2 associated with prolonged
      survival.
AB  - Ataxia telangiectasia (AT) and ataxia oculomotor apraxia type 2 (AOA2) are
      autosomal recessive ataxias caused by mutations in genes involved in maintaining
      DNA integrity. Lifespan in AT is greatly shortened (20s-30s) due to increased
      susceptibility to malignancies (leukemia/lymphoma). Lifespan in AOA2 is
      uncertain. We describe a woman with variant AT with two novel mutations in ATM
      (IVS14+2T>G and 5825C>T, p.A1942V) who died at age 48 with pancreatic
      adenocarcinoma. Her mutations are associated with an unusually long life for AT
      and with a cancer rarely associated with that disease. We also describe two
      siblings with AOA2, heterozygous for two novel mutations in senataxin (3 bp
      deletion c.343-345 and 1398T>G, p.I466M) who have survived into their 70s,
      allowing us to characterize the longitudinal course of AOA2. In contrast to AT,
      we show that persons with AOA2 can experience a prolonged lifespan with
      considerable motor disability.

PMID- 24090760
TI  - The clinical and pathological phenotypes of frontotemporal dementia with C9ORF72
      mutations.
AB  - An expanded hexanucleotide repeat in the chromosome 9 open reading frame 72
      (C9ORF72), on chromosome 9p21, has recently been identified as a major cause of
      familial frontotemporal dementia (FTD). The neuropathology and clinical
      characteristics associated with C9ORF72 mutations are heterogeneous with the
      unknown pathomechanism. These cases were reported with a series of
      neuropathology, including TDP-43 pathology, ubiquilin (UBQLN) pathology, p62
      pathology, microglial pathology, RNA-binding protein pathology and pathology
      associated with dipeptide-repeat (DPR) proteins. TDP-43 positive neuropathology
      was important in FTD patients with the mutations. Nevertheless, the majority of
      reports agree with a special pattern of neuropathology with p62 positive, TDP-43
      negative inclusions being a consistent feature. Although subjects with the
      C9ORF72 mutations more frequently present with earlier onset age, earlier death,
      a shortened survival and a positive family history, most of the subjects present
      with typical clinical features of FTD. All these findings support that the
      C9ORF72 mutations become important newly recognized causes of FTD, providing a
      more detailed characterization of the associated clinical and pathological
      features. The following review summarizes the pathological development of FTD
      associated with C9ORF72, the clinical and pathological features of this cohort,
      some pathological mechanism hypotheses, and describes their phenotypic range and
      overlap with other neurodegenerative diseases. 

PMID- 24090761
TI  - Exome sequencing identifies novel compound heterozygous mutations in SPG11 that
      cause autosomal recessive hereditary spastic paraplegia.
AB  - Hereditary spastic paraplegia (HSP) is a neurodegenerative disease characterized
      by progressive weakness and spasticity of the lower limbs, in complicated forms,
      with additional neurological signs. To identify the genotype and characterize the
      phenotype in a Chinese HSP family, ten subjects from the family were examined
      through detailed clinical evaluations, auxiliary examinations and genetic tests.
      Using a combined approach of whole-exome sequencing and candidate mutation
      validation, we identified novel compound heterozygous mutations in the SPG11 gene
      of the patients as follows: a nonsense mutation c.6856C>T (p.R2286X) in exon 38
      and a deletion mutation c.2863delG (p.Glu955Lysfs*8) in exon 16. Both mutations
      co-segregated with the phenotype in this family and were absent in 100 normal
      Chinese individuals. Our finding suggests that the novel compound heterozygous
      mutations in SPG11 are associated with HSP. We were able to assess the future
      risk of HSP in healthy younger family members using genetic detection, and
      provide prenatal diagnoses for the family members. Furthermore, to some extent,
      this new finding enriches the information on SPG11 and may provide a new basis
      for the genetic diagnosis of HSP. 

PMID- 24090762
TI  - Fulminant cerebellitis with radiological recurrence in an adult patient with
      Crohn's disease.
AB  - There are few reports of cerebellitis in adults and reports of recurrent
      cerebellitis are extremely rare. This report highlights both the fulminant course
      that may follow cerebellitis and a potentially important association with Crohn's
      disease. A 41-year-old man presented with headache and cerebellar dysfunction a
      month after ileo-colonic resection for Crohn's disease. MRI demonstrated T2
      signal abnormalities, pial enhancement and cerebellar enlargement. His course was
      complicated by obstructive hydrocephalus, intraventricular hemorrhage associated
      with external ventricular drain placement and left transverse sinus venous
      thrombosis. Treatment with high-dose intravenous steroids and anti-coagulation
      resulted in improvement. Asymptomatic radiological worsening 13 months after
      initial presentation occurred during a relapse of Crohn's disease. He was treated
      with intravenous steroids and maintenance azathioprine for his Crohn's and
      suspected immune mediated cerebellitis. At last follow-up 4 years after initial
      presentation his clinical status remained unchanged and radiological changes had
      stabilized. Adult onset cerebellitis may be fulminant and recurrent. Early
      immunotherapy in acute relapsing cerebellitis may speed recovery and prevent
      recurrence. Onset and radiological relapse of cerebellitis during Crohn's disease
      flare-ups as in our case possibly suggests a shared autoimmune pathogenesis.

PMID- 24090763
TI  - Reconstruction of through-and-through oral cavity defects with folded extended
      vertical lower trapezius island myocutaneous flap.
AB  - Reconstruction of through-and-through defects of the head and neck is a
      challenge. In this clinical study we assessed the feasibility of the folded,
      extended, vertical, lower trapezius island myocutaneous flap (TIMF) for the
      reconstruction of 16 large through-and-through defects of the oral cavity, which
      were reconstructed after resection of oral cancer. The skin paddle was 5-7 cm
      wide and 11-20 cm long. The folded flap provides both inner and outer linings for
      through-and-through defects, and all the flaps survived. The appearance of the
      head and neck was acceptable, and oral function was satisfactory. The folded
      extended vertical lower TIMF is a large, simple, and reliable flap that is
      preferred for the reconstruction of large through-and-through defects after
      resection of oral carcinoma.

PMID- 24090764
TI  - How do I manage an acute injury to the facial nerve?
AB  - Paralysis of the facial nerve is a cause of considerable functional and aesthetic
      disfigurement. Damage to the upper trunk can result in eye complications with the
      risk of exposure keratitis. Numerous factors influence the therapeutic strategy:
      the cause of the injury, the time elapsed since injury, functional impairment,
      and the likelihood of recovery. We discuss the management of an acute injury to
      the facial nerve and focus on the surgical options.

PMID- 24090765
TI  - Citation for Mr Satyesh Parmar for the BAOMS Surgery Prize 2012.

PMID- 24090766
TI  - DeltaFosB induction correlates inversely with CB1 receptor desensitization in a
      brain region-dependent manner following repeated Delta9-THC administration.
AB  - Repeated Delta(9)-tetrahydrocannabinol (THC) administration produces
      desensitization and downregulation of cannabinoid type 1 receptors (CB1Rs) in the
      brain, but the magnitude of these adaptations varies among regions. CB1Rs in the
      striatum and its output regions exhibit the least magnitude and slowest
      development of desensitization and downregulation. The molecular mechanisms that
      confer these region-dependent differences are not known. The stable transcription
      factor, DeltaFosB, is induced in the striatum following repeated THC
      administration and could regulate CB1Rs. To directly compare the regional profile
      of DeltaFosB induction and CB1R desensitization and downregulation, mice were
      treated with THC (10 mg/kg) or vehicle for 13.5 days. CP55,940-stimulated
      [(35)S]GTPgammaS autoradiography and immunohistochemistry were performed to
      measure CB1R desensitization and downregulation, respectively, and DeltaFosB
      expression was measured by immunoblot. Significant CB1R desensitization and
      downregulation occurred in the prefrontal cortex, lateral amygdala and
      hippocampus; desensitization was found in the basomedial amygdala and no changes
      were seen in remaining regions. DeltaFosB was induced in the prefrontal cortex,
      caudate-putamen, nucleus accumbens and lateral amygdala. An inverse regional
      relationship between DeltaFosB expression and CB1R desensitization was found,
      such that regions with the greatest DeltaFosB induction did not exhibit CB1R
      desensitization and areas without DeltaFosB induction had the greatest
      desensitization, with remaining regions exhibiting intermediate levels of both.
      Dual immunohistochemistry in the striatum showed both CB1R co-localization with
      DeltaFosB in cells and CB1R puncta surrounding DeltaFosB-positive cells. THC
      induced expression of DeltaFosB was absent in the striatum of CB1R knockout mice.
      These data suggest that transcriptional targets of DeltaFosB might inhibit CB1R
      desensitization and/or that DeltaFosB induction could be limited by CB1R
      desensitization.

PMID- 24090767
TI  - Alignment of multiple glial cell populations in 3D nanofiber scaffolds: toward
      the development of multicellular implantable scaffolds for repair of neural
      injury.
AB  - Non-neuronal cells of the central nervous system (CNS), termed "neuroglia," play
      critical roles in neural regeneration; therefore, replacement of glial
      populations via implantable nanofabricated devices (providing a growth-permissive
      niche) is a promising strategy to enhance repair. Most constructs developed to
      date have lacked three-dimensionality, multiple glial populations and control
      over spatial orientations, limiting their ability to mimic in vivo
      neurocytoarchitecture. We describe a facile technique to incorporate multiple
      glial cell populations [astrocytes, oligodendrocyte precursor cells (OPCs) and
      oligodendrocytes] within a three-dimensional (3D) nanofabricated construct.
      Highly aligned nanofibers could induce elongation of astrocytes, while OPC
      survival, elongation and maturation required pre-aligned astrocytes. The
      potential to scale-up the numbers of constituent nanofiber layers is demonstrated
      with astrocytes. Such complex implantable constructs with multiple glial sub
      populations in defined 3D orientations could represent an effective approach to
      reconstruct glial circuitry in neural injury sites. FROM THE CLINICAL EDITOR:
      Clinically available methods to enhance nervous tissue regeneration remain scarce
      despite decades of research. In this study, a novel 3D nanofabricated construct
      is demonstrated, that includes populations of astrocytes, oligodendrocyte
      precursor cells and oligodendrocytes providing a well-orchestrated glial
      microenvironment for more efficient central nervous system repair.

PMID- 24090768
TI  - Femtosecond laser-patterned nanopore arrays for surface-mediated peptide
      treatment.
AB  - The major goal of this study was to create easy-to-use, reusable substrates
      capable of storing any peptides or bioactive molecules for a desired period of
      time until cells uptake them without the need for bioactive molecule or peptide
      specific techniques. Nanopore arrays of uniform size and distribution were
      machined into fused silica substrates using femtosecond laser ablation and loaded
      with peptides by simple adsorption. The nanopore substrates were validated by
      examining the effect of N-acetyl-seryl-aspartyl-lysyl-proline (Ac-SDKP) loaded
      nanopores on macrophage phagocytosis and intracellular production of reactive
      oxygen species (ROS) with and without the pro-inflammatory lipopolysaccharide
      (LPS). Our results demonstrated that nanopores were generated in a uniform array
      fashion. Ac-SDKP peptides were stably stored in nanopores and internalized by
      macrophages. Significant reductions in ROS production and phagocytosis in
      macrophages were observed over control substrates, even in combination with LPS
      stimulation, indicating that loading Ac-SDKP peptides in pores significantly
      improved the anti-inflammatory effects. FROM THE CLINICAL EDITOR: This team of
      scientists intended to create easy-to-use, reusable substrates for storing
      peptides or bioactive molecules for a desired period of time before cellular
      uptake occurs, and without the need for bioactive molecule or peptide-specific
      techniques. They demonstrate the successful generation of nanopores in a uniform
      array that stably stores Ac-SDKP peptides in the nanopores. When peptides were
      internalized by macrophages, significant reductions in ROS production and
      phagocytosis were observed, indicating improved anti-inflammatory effects.

PMID- 24090769
TI  - Translational research on aging: clinical epidemiology as a bridge between the
      sciences.

PMID- 24090771
TI  - Clarifying the role of the 22q11.2 microdeletion in juvenile myoclonic epilepsy.

PMID- 24090772
TI  - Systems biology, complexity, and the impact on antiepileptic drug discovery.
AB  - The number of available anticonvulsant drugs increased in the period spanning
      over more than a century, amounting to the current panoply of nearly two dozen so
      called antiepileptic drugs (AEDs). However, none of them actually
      prevents/reduces the post-brain insult development of epilepsy in man, and in no
      less than a third of patients with epilepsy, the seizures are not drug
      controlled. Plausibly, the enduring limitation of AEDs' efficacy derives from the
      insufficient understanding of epileptic pathology. This review pinpoints the
      unbalanced reductionism of the analytic approaches that overlook the intrinsic
      complexity of epilepsy and of the drug resistance in epilepsy as the core
      conceptual flaw hampering the discovery of truly antiepileptogenic drugs. A
      rising awareness of the complexity of epileptic pathology is, however, brought
      about by the emergence of nonreductionist systems biology (SB) that considers the
      networks of interactions underlying the normal organismic functions and of SB
      based systems (network) pharmacology that aims to restore pathological networks.
      By now, the systems pharmacology approaches of AED discovery are fairly meager,
      but their forthcoming development is both a necessity and a realistic prospect,
      explored in this review.

PMID- 24090770
TI  - Biology of telomeres: importance in etiology of esophageal cancer and as
      therapeutic target.
AB  - The purpose of this review is to highlight the importance of telomeres, the
      mechanisms implicated in their maintenance, and their role in the etiology as
      well as the treatment of human esophageal cancer. We will also discuss the role
      of telomeres in the maintenance and preservation of genomic integrity, the
      consequences of telomere dysfunction, and the various factors that may affect
      telomere health in esophageal tissue predisposing it to oncogenesis. There has
      been growing evidence that telomeres, which can be affected by various intrinsic
      and extrinsic factors, contribute to genomic instability, oncogenesis, as well as
      proliferation of cancer cells. Telomeres are the protective DNA-protein complexes
      at chromosome ends. Telomeric DNA undergoes progressive shortening with age
      leading to cellular senescence and/or apoptosis. If senescence/apoptosis is
      prevented as a consequence of specific genomic changes, continued proliferation
      leads to very short (ie, dysfunctional) telomeres that can potentially cause
      genomic instability, thus, increasing the risk for activation of telomere
      maintenance mechanisms and oncogenesis. Like many other cancers, esophageal
      cancer cells have short telomeres and elevated telomerase, the enzyme that
      maintains telomeres in most cancer cells. Homologous recombination, which is
      implicated in the alternate pathway of telomere elongation, is also elevated in
      Barrett's-associated esophageal adenocarcinoma. Evidence from our laboratory
      indicates that both telomerase and homologous recombination contribute to
      telomere maintenance, DNA repair, and the ongoing survival of esophageal cancer
      cells. This indicates that telomere maintenance mechanisms may potentially be
      targeted to make esophageal cancer cells static. The rate at which telomeres in
      healthy cells shorten is determined by a number of intrinsic and extrinsic
      factors, including those associated with lifestyle. Avoidance of factors that may
      directly or indirectly injure esophageal tissue including its telomeric and other
      genomic DNA can not only reduce the risk of development of esophageal cancer but
      may also have positive impact on overall health and lifespan. 

PMID- 24090773
TI  - Malay public attitudes toward epilepsy (PATE) scale: translation and psychometric
      evaluation.
AB  - INTRODUCTION: None of the quantitative scales for public attitudes toward
      epilepsy had been translated to Malay language. This study aimed to translate and
      test the validity and reliability of a Malay version of the Public Attitudes
      Toward Epilepsy (PATE) scale. METHOD: The translation was performed according to
      standard principles and tested in 140 Malay-speaking adults aged more than 18
      years for psychometric validation. RESULTS: The items in each domain had similar
      standard deviations (equal item variance), ranging from 0.90 to 1.00 in the
      personal domain and from 0.87 to 1.23 in the general domain. The correlation
      between an item and its domain was 0.4 and above for all items and was higher
      than the correlation with the other domain. Multitrait analysis showed that the
      Malay PATE had a similar variance, floor and ceiling effects, and relative
      relationship between the domains as the original PATE. The Malay PATE scale
      showed a similar correlation with almost all demographic variables except age.
      Item means were generally clustered in the factor analysis as the hypothesized
      domains, except those for items 1 and 2. The Cronbach's alpha values were within
      acceptable range (0.757 and 0.716 for the general and personal domains,
      respectively). CONCLUSION: The Malay PATE scale is a validated and reliable
      translated version for measuring public attitudes toward epilepsy.

PMID- 24090774
TI  - Integration of gray matter nodules into functional cortical circuits in
      periventricular heterotopia.
AB  - Alterations in neuronal circuitry are recognized as an important substrate of
      many neurological disorders, including epilepsy. Patients with the developmental
      brain malformation of periventricular nodular heterotopia (PNH) often have both
      seizures and dyslexia, and there is evidence to suggest that aberrant neuronal
      connectivity underlies both of these clinical features. We used task-based
      functional MRI (fMRI) to determine whether heterotopic nodules of gray matter in
      this condition are integrated into functional cortical circuits. Blood
      oxygenation level-dependent (BOLD) fMRI was acquired in eight participants with
      PNH during the performance of reading-related tasks. Evidence of neural
      activation within heterotopic gray matter was identified, and regions of cortical
      coactivation were then mapped systematically. Findings were correlated with
      resting-state functional connectivity results and with performance on the fMRI
      reading-related tasks. Six participants (75%) demonstrated activation within at
      least one region of gray matter heterotopia. Cortical areas directly overlying
      the heterotopia were usually coactivated (60%), as were areas known to have
      functional connectivity to the heterotopia in the task-free resting state (73%).
      Six of seven (86%) primary task contrasts resulted in heterotopia activation in
      at least one participant. Activation was most commonly seen during rapid naming
      of visual stimuli, a characteristic impairment in this patient population. Our
      findings represent a systematic demonstration that heterotopic gray matter can be
      metabolically coactivated in a neuronal migration disorder associated with
      epilepsy and dyslexia. Gray matter nodules were most commonly coactivated with
      the anatomically overlying cortex and other regions with resting-state
      connectivity to heterotopia. These results have broader implications for
      understanding the network pathogenesis of both seizures and reading disabilities.

PMID- 24090775
TI  - Risks of subsequent epilepsy among patients with hypertensive encephalopathy: a
      nationwide population-based study.
AB  - BACKGROUND: To determine whether the diagnosis of hypertensive encephalopathy
      (HE) is linked to an increased risk of subsequent epilepsy by using a nationwide
      population-based retrospective study. METHODS: Our study featured a study cohort
      and a comparison cohort. The study cohort consisted of all patients with newly
      diagnosed HE between 1997 and 2010, compiled from universal insurance claims data
      on patients with hypertension taken from the National Health Insurance Research
      Database. The comparison cohort comprised the remaining hypertensive patients
      without encephalopathy. The follow-up period was terminated following the
      development of epilepsy, death, withdrawal from the National Health Insurance
      system, or the end of 2010. We determined the cumulative incidences and hazard
      ratios (HRs) of epilepsy development. RESULTS: The incidence of subsequent
      epilepsy was 2.25-fold higher in the patients with HE than in comparisons (4.17
      vs. 1.85 per 1000 person-years), with an adjusted HR of 2.06 (95% CI=1.66-2.56)
      in the multivariable Cox proportional-hazards regression analysis. The incidence
      of epilepsy was higher in men, younger patients with HE, and those with brain
      disorders. CONCLUSIONS: We found that, in Taiwan, patients with HE are at an
      increased risk of subsequent epilepsy. Physicians should be aware of HE's link to
      epilepsy when assessing patients with HE.

PMID- 24090776
TI  - Medication adherence in patients with epilepsy after a single neurologist visit
      in rural India.
AB  - In India, there are less than 2000 neurologists, and an estimated 5 million
      patients have epilepsy. With such limited neurological care available, novel
      treatment approaches for epilepsy are necessary. This study evaluates the
      effectiveness of a mobile clinic in treating epilepsy. Patients from two mobile
      clinic stop locations in northern India were contacted 7 and 9 months later for
      an in-person or over-the-phone survey. Of the 306 eligible patients who had been
      seen in the selected cities, 142 were interviewed, 72.5% of whom reported that
      they were still taking medications; among medication-naive patients, 50.9% were
      still taking medications. The one-time clinic is effective and could be a model
      for working towards reducing the wide rural epilepsy treatment gap in India and
      other countries. Creative follow-up mechanisms need to be developed.

PMID- 24090777
TI  - Preschool behavioral problems in children prenatally exposed to antiepileptic
      drugs - a follow-up study.
AB  - We studied the association between maternal epilepsy, antiepileptic drug (AED)
      treatment, and behavioral problems in preschool children. In the Danish National
      Birth Cohort, we identified 4- to 5-year-old children whose mothers had epilepsy
      and received AED treatment (n=133) or not (n=304) during pregnancy and compared
      them with randomly selected children whose mothers did not have epilepsy
      (n=1193). The children's behavioral problems were assessed by the use of the
      Strengths and Difficulties Questionnaire (SDQ). Children prenatally exposed to
      AEDs more often had an abnormal total SDQ score as compared with children of
      women without epilepsy (odds ratio (OR)=4.8 (95% CI: 1.9-12.1)) and as compared
      with children of women with epilepsy who were not treated with AEDs during their
      pregnancy (OR=4.0 (95% CI: 1.3-12.8)). In conclusion, prenatal AED exposure may
      increase the risk of behavioral problems in preschool children even after
      adjustments for potential confounders and maternal epilepsy. 

PMID- 24090778
TI  - Dissociative seizures--a critical review and perspective.
AB  - Dissociative seizures are commonly recognized as both a challenging and a poorly
      understood condition. Though research and publication activity is high, advances
      in knowledge and insight seem only moderate in recent years. This review focuses
      on some relevant problematic issues, which might account for a still
      unsatisfactory research state. A general tendency to deal with dissociative
      seizures as an assumed disorder in its own nosological right and not as a sole
      symptom of an underlying psychiatric disorder is most likely one of the major
      roots of the problem. Unfavorable impacts of this confusion pertaining to
      clinical management, therapy, and outcome of dissociative seizures are discussed.
      An alternative point of view, based on the immanent psychiatric and psychodynamic
      roots of dissociative seizures, is considered. 

PMID- 24090779
TI  - [Surgical treatment of metastatic urothelial carcinoma of the bladder: Review of
      the Cancer Committee of the French Association of Urology].
AB  - INTRODUCTION: The role of surgery in the treatment of patients with metastatic
      urothelial bladder cancer is controversial. The aim was to review situations
      where surgical resection of the bladder tumor and/or metastatic urothelial
      carcinoma has been reported and analyze its results. MATERIALS AND METHODS: A
      bibliographic research in French and English using the keywords BCG, bladder
      cancer, metastases, cystectomy, metastasectomy, radiotherapy, curative treatment
      and palliative treatment was performed, 177 articles have been reviewed, and 18
      have been selected. RESULTS: Synchronous or metachronous urothelial carcinoma
      metastases were diagnosed in 4 and 50% of the cases, respectively. The surgical
      treatment of metastatic urothelial carcinoma of the bladder has been proposed to
      achieve oncologic resection of all detectable lesions after a first-line
      chemotherapy or to treat symptoms, which were refractory to other treatment
      modalities. In achieving complete resection of the primary tumor and metastases
      after MVAC chemotherapies, the 5years overall survival was 28%. CONCLUSION: There
      was no evidence in favouring surgical treatment of metastatic urothelial
      carcinoma. Considering the high perioperative mortality rate of cystectomy in
      imperative indications, particularly in the case of hematuria, all therapeutic
      alternatives must have been exhausted and urine derived in the simplest way.

PMID- 24090780
TI  - [Failed hypospadias repair].
AB  - Reoperating an hypospadias requires a reconstructive strategy that considers the
      patient's disturbing symptoms, located on the urethra (stenosis, fistula,
      persistent hypospadias, urethral hair) as well as on cavernous bodies and penile
      skin. Though experience validates it, this global and gradual approach has been
      barely described. It takes up latest hypospadiology work through several steps:
      after urethroscopy, penis is freed from penile skin in order to treat first a
      potential residual curvature in four steps. Then, the urethral issue is fixed
      differently according to the state of the penile urethra. In addition, a buccal
      mucosal urethroplasty will be likely to be occurred, in one or two times. 

PMID- 24090781
TI  - [A new technique for ensuring negative surgical margins during partial
      nephrectomy: the ex vivo ultrasound control].
AB  - OBJECTIVE: To evaluate the feasibility and the efficiency of intraoperative ex
      vivo ultrasound of resection margins in patients undergoing partial nephrectomy
      by urologist. PATIENTS AND METHODS: Patients undergoing partial nephrectomy from
      July 2010 to November 2012 for T1-T2 renal tumors were included in analysis.
      Tumor margin status was immediately determined by ex vivo ultrasound done by the
      surgeon himself. Results were compared with margin status on definitive
      pathological evaluation. RESULTS: A total of 26 men and 15 women with a median
      age of 61 (30-82) years old were included in analysis. Intraoperative ex vivo
      ultrasound revealed negative surgical margins in 38 cases and positive margins in
      two. Final pathological results revealed negative margins in all except one case.
      Ultrasound sensitivity and specificity were 100% and 97%, respectively. Mean
      ultrasound duration was 1minute+/-1. Mean tumor and margin sizes were 3.4+/-1.8cm
      and 2.38+/-1.76mm, respectively. CONCLUSION: Intraoperative ex vivo ultrasound of
      resection margins in patients undergoing partial nephrectomy by a urologist
      seemed to be feasible, efficient and easy.

PMID- 24090782
TI  - [Multicentric evaluation of a self-screening questionnaire for occupational
      bladder cancer].
AB  - OBJECTIVE: Evaluate a self-screening questionnaire for bladder cancer of
      occupational origin and analyse an influence of exposure to a carcinogen bladder
      tumor on prognosis. PATIENTS AND METHODS: Five hundred and thirty-one patients
      followed, between 2005 and 2010, for bladder cancer in two university centers
      have received a self-screening questionnaire derived from questionnaire KVP 08.
      Patients who responded positively to at least one of the items were considered to
      have a self-screening questionnaire "positive". Patients were finally invited to
      take an appointment for consultation in occupational pathology. RESULTS: The
      response rate to self-screening questionnaire was 39.9% (212/531). It was
      "positive" in 82 cases (38.7%). Among the 82 patients with a self-screening
      questionnaire "positive", 46 patients consulted in occupational pathology (56%).
      Occupational exposure to a bladder carcinogen was documented in 91.3% of cases.
      Among the 22 patients who consulted in occupational pathology with a self
      screening questionnaire "negative", an occupational exposure to a bladder
      carcinogen was documented in 13.6% of cases. The sensibility of the self
      screening questionnaire was 91.3%, the specificity 86.4% and the accuracy 89.7%.
      The relative risk to have an occupational exposure if the self-screening
      questionnaire was "positive" was 6.69. The analysis of groups "positive" versus
      "negative" does not reveal any statistically significant difference in terms of
      tumor aggressiveness and disease-free survival. CONCLUSION: The self-screening
      questionnaire was considered relevant with good reliability for detection of
      occupational exposure to a bladder carcinogen.

PMID- 24090783
TI  - [Sub-urethral sling Advance((r)) midterm results: patient selection and
      predictors of success].
AB  - INTRODUCTION AND OBJECTIVES: Sub-urethral trans-obturator male slings have been
      propose to treat men urinary incontinence. Medium term results are lacking: only
      one study has been published. AIM: To evaluate the efficacy of the sub-urethral
      sling Advance((r)) (American Medical System, Minnetonka, MN, USA) and determinate
      factor of success. MATERIALS AND METHODS: Single center retrospective study of
      patients implanted with an Advance((r)) for urinary incontinence after radical
      prostatectomy. The degree of incontinence was evaluated by number of pads used
      per days: mild (use of 1 to 2 pads/day), moderate (3 to 4p/day) and severe
      (>=5p/day). The "Cure" was defined as no pad or just one for "security reason"
      and "improved" as decreased more than 50% of pads use. RESULTS: Between October
      2007 and November 2009, 69 slings were implanted. Mean follow-up was 32.4months
      (+/-8.4months). Before treatment, 37.68% of the patients suffered from mild,
      42.03% moderate and 20.29% severe urinary incontinence. At midterm, 21.8% of the
      patients were cured and 50.7% cured or improved. For patients who suffered from
      mild or moderate urinary incontinence, 23.6% were cured and 58.2% were cured or
      improved. The cure rate decreased with the severity of incontinence. It was
      respectively 30.8%, 17.2% and 14.2% for mild, moderate and severe incontinence.
      Failure rate was more important with severe incontinence: 78%. For patients with
      urethral fence pressure less than 57cmH2O, the risk of failure was multiply by
      6.6. No severe complication was noted during follow-up. Only one male sling was
      removed. CONCLUSIONS: At midterm, one patient on five was cure and half was cured
      or improved. The technique presented an acceptable morbidity and a good
      tolerance. Two predictors of success were identified: severity of incontinence
      and residual sphincter function. Good candidates used less than three pads per
      day.

PMID- 24090784
TI  - [Ajust((r)): prospective study and 1-year follow-up - a series of 60 female
      patients].
AB  - OBJECTIVES: Evaluate functional and anatomical outcomes as well as complications,
      1year after the implantation of the Ajust((r)) sub-urethral adjustable single
      incision sling. STUDY DESIGN: Prospective study on 60 female patients suffering
      from stress urinary or mixed urinary incontinence with quality of life
      assessment. Ambulatory surgeries were performed under local anesthesia with or
      without sedation. Pain was evaluated using the VAS scale. Postoperative follow-up
      was performed at 2 and 12months. RESULTS: Forty-eight patients suffered from
      stress incontinence only, with one of them suffering from sphincter deficiency,
      and the remaining 12 suffered from mixed urinary incontinence. Mean surgery time
      was 7.15minutes. All patients received a local anesthesia, and 33 were sedated.
      Per-operative pain level was equal to 31.8/100, and 17/100 upon discharge. A
      100mL per-operative hemorrhage was described. At 2-month follow-up, four de novo
      urgency, four de novo dysuria, one urinary infection, 11 palpable lateral cords,
      12 moderate postoperative pain were described. At 1-year follow-up, two mesh
      exposures formed, including one expelled anchor for one of them. At 1year, cure
      rate, improvement and failure rate were respectively 89.6%, 6.9% and 3.4%.
      Quality of life indexes were significantly improved. One patient required a new
      surgery at 2months, due to initial failure. CONCLUSIONS: The efficacy of this
      mini-invasive sling, without specific complication, must be compared with the
      other classic sub-uretral slings.

PMID- 24090785
TI  - [Social integration of women operated for obstetric urogenital fistula].
AB  - OBJECTIVE: To study the social integration of women supported in the urology
      department of the University Hospital of Point G for obstetric urogenital
      fistula. PATIENTS AND METHOD: Prospective study conducted over a period of 13
      months from June 2008 to June 2009 in the Department of Urology at the University
      Hospital of Point G. The study included all patients who have been operated on at
      least twice for obstetric fistula genitourinary. Records of surgical, medical
      records and tracking sheets for each patient were the media database. RESULTS:
      Situation before treatment: before surgical treatment, 76.92% of patients were
      rejected by their spouses. The family attended the patient in 84.62% of cases.
      Situation after treatment: after treatment, 90.31% of women with fistula lived in
      the matrimonial home or family. The resumption of business activity was announced
      by 11.2% of patients. Among the women, 93.7% participated in housework. The
      number of patient intervention ranged from two to five. Healing (fistula closed
      and no sphincter dysfunction) was complete in 50% of cases. Among the women,
      11.54% had sphincter dysfunction after closure of the fistula, which makes a
      total of fistula closed more than 61% after at least two attempts. CONCLUSION:
      The urogenital fistulas are not a fatal disease but is a real handicap for women
      who suffer to conduct a socio-cultural and economic mainstream. Generally
      excluded from the ongoing operations of the company, these women are more
      integrated after successful surgical treatment of the fistula.

PMID- 24090786
TI  - [Urinary ascites, uroperitoneum and urinary peritonitis in children: management
      of nine case reports in Madagascar].
AB  - OBJECTIVE: To evaluate the frequency of urinary peritonitis in children and to
      highlight its terms of management in a country with limited resources. PATIENTS
      AND METHODS: We retrospectively observed nine case reports of urinary peritonitis
      collected in surgical reanimation service at the CHU of Antananarivo, from 1st
      January 2009 to 31 December 2012. RESULTS: Urinary peritonitis accounts 0.5% of
      all pediatric abdominal emergencies and 5% of pediatric urological emergencies
      collected in our service during study period. Three etiologies were traumatic
      bladder rupture, one bladder iatrogenic rupture, four secondary to obstructive
      uropathy and one other after cystolithotomy. We found a new case of posttraumatic
      transverse rupture of the bladder neck. Among obstructive uropathy observed,
      there were two cases of posterior urethral valves and two cases of ureteralpelvic
      junction obstruction. Clinical expression was dominated by fever, with abdominal
      distention and defense. In majority of cases, etiological diagnosis was made
      intraoperatively. The surgical treatment by laparotomy was performed under cover
      of systemic antibiotic therapy. Evolution was complicated with sepsis in three
      cases and acute renal failure in both cases. Surgical follow-up without
      complication were observed in four cases. A child has died to septic shock and
      multivisceral failure. CONCLUSION: Unlike urinary ascites resulting a
      transperitoneal extravasation of urine, uroperitoneum was a fistula between
      adominal cavity and content of the urinary tract. Urinary ascites was a rare
      cause of peritonitis. In contrast, uroperitoneum caused peritonitis quickly.
      Urinary peritonitis was a rare entity but severe prognosis in children. In
      majority of cases, etiological diagnosis was made intraoperatively.

PMID- 24090787
TI  - [Critical haematuria after prostate biopsies with RIVAROXABAN. Case report].
AB  - Managing patients with new oral anticoagulants in perioperative period is not yet
      well protocolized. We report a clinical case of a critical haematuria after
      prostate biopsies to a patient treated with RIVAROXABAN. Monitoring and treatment
      of the haematuria have been difficult due to the lack of biological control and
      antidote for this treatment. 

PMID- 24090788
TI  - [AJUSTTM: prospective study and 1-year follow-up - a series of 60 female
      patients].

PMID- 24090789
TI  - Treating allergic rhinitis with depot-steroid injections increase risk of
      osteoporosis and diabetes.
AB  - BACKGROUND: In Denmark, 23% of the adult population have allergic rhinitis. We
      have previously demonstrated that a majority of hay fever patients are treated
      with depot-steroid injections in violation of the guidelines. It has been
      hypothesised that 1-2 annual depot-steroid injections are not harmful to the
      patient. OBJECTIVES: Investigate if the depot-steroid treatment of allergic
      rhinitis instead of immunotherapy increases risk of steroid-related diseases.
      METHODS: A retrospective study based on Danish National Registries 1995-2011
      covering diagnoses, medications, as well as clinical outcomes. The main analysis
      was time dependent poisson regression models with results presented as rate
      ratios (RR), and incidence per 1000 patient years. Steroid use was defined as
      minimum one injection during April-July for at least three consecutive years.
      Treatment with specific immunotherapy against grass, birch or both was used as
      non-steroid control group. Relative risk of adverse outcomes such as
      osteoporosis, infections, diabetes and/or tendon rupture was investigated.
      RESULTS: We identified 47,382 individuals with rhinitis; 55.8% treated with
      steroids, 37.6% with immunotherapy, and 6.7% with both. No significant
      differences in infections or tendon rupture were observed. For steroid treatment
      RR of diabetes was 1.5 (95% CI: 1.3-1.8; P < 0.001), incidence 3.9 (95% CI: 3.5
      4.3), and RR of osteoporosis was 1.2 (95% CI: 1.0-1.5; P = 0.023), incidence 2.8
      (95% CI: 2.5-3.1). Risk of diabetes culminated within the first two years of
      treatment start. CONCLUSIONS: Compared to immunotherapy regular use of depot
      steroid injections to treat allergic rhinitis is associated with increased risk
      of being diagnosed with diabetes and osteoporosis. CLINICAL IMPLICATIONS:
      Treating seasonal allergic rhinitis with depot-steroid injections should be
      abandoned and replaced with immunotherapy, as annual depot-steroid treatment is
      associated with increased risk of diabetes and osteoporosis.

PMID- 24090790
TI  - [Organs at risk in radiation therapy of head and neck tumors: practical aspects
      in their delineation and normal tissue tolerance].
AB  - The aim of this article is to provide some practical guidelines for the
      delineation of organs at risk in intensity-modulated radiation therapy (IMRT) in
      head and neck cancer, drawn from anatomic, radiology, physiopathology date which
      will take into account the daily imperatives of radiation oncologists.
      Standardizing the delineation of organs at risk by consensus, might help for an
      objective comparison of toxicities induced by radiotherapy. 

PMID- 24090791
TI  - Changes in the development of striatum are involved in repetitive behavior in
      autism.
AB  - BACKGROUND: Repetitive behavior is a core feature of autism and has been linked
      to differences in striatum. In addition, the brain changes associated with autism
      appear to vary with age. However, most studies investigating striatal differences
      in autism are cross-sectional, limiting inferences on development. In this study,
      we set out to 1) investigate striatal development in autism, using a longitudinal
      design; and 2) examine the relationship between striatal development and
      repetitive behavior. METHODS: We acquired longitudinal structural magnetic
      resonance imaging scans from 86 individuals (49 children with autism, 37 matched
      control subjects). Each individual was scanned twice, with a mean scan interval
      time of 2.4 years. Mean age was 9.9 years at time 1 and 12.3 years at time 2.
      Striatal structures were traced manually with high reliability. Multivariate
      analyses of variance were used to investigate differences in brain development
      between diagnostic groups. To examine the relationship with behavior,
      correlations between changes in brain volumes and clinical measures were
      calculated. RESULTS: Our results showed an increase in the growth rate of
      striatal structures for individuals with autism compared with control subjects.
      The effect was specific to caudate nucleus, where growth rate was doubled.
      Second, faster striatal growth was correlated with more severe repetitive
      behavior (insistence on sameness) at the preschool age. CONCLUSIONS: This
      longitudinal study of brain development in autism confirms the involvement of
      striatum in repetitive behavior. Furthermore, it underscores the significance of
      brain development in autism, as the severity of repetitive behavior was related
      to striatal growth, rather than volume per se.

PMID- 24090792
TI  - A mouse model that recapitulates cardinal features of the 15q13.3 microdeletion
      syndrome including schizophrenia- and epilepsy-related alterations.
AB  - BACKGROUND: Genome-wide scans have uncovered rare copy number variants conferring
      high risk of psychiatric disorders. The 15q13.3 microdeletion is associated with
      a considerably increased risk of idiopathic generalized epilepsy, intellectual
      disability, and schizophrenia. METHODS: A 15q13.3 microdeletion mouse model
      (Df[h15q13]/+) was generated by hemizygous deletion of the orthologous region and
      characterized with focus on schizophrenia- and epilepsy-relevant parameters.
      RESULTS: Df(h15q13)/+ mice showed marked changes in neuronal excitability in
      acute seizure assays, with increased propensity to develop myoclonic and absence
      like seizures but decreased propensity for clonic and tonic seizures.
      Furthermore, they had impaired long-term spatial reference memory and a decreased
      theta frequency in hippocampus and prefrontal cortex. Electroencephalogram
      characterization revealed auditory processing deficits similar to those observed
      in schizophrenia. Gamma band power was increased during active state, but evoked
      gamma power following auditory stimulus (40 Hz) was dramatically reduced,
      mirroring observations in patients with schizophrenia. In addition, Df(h15q13)/+
      mice showed schizophrenia-like decreases in amplitudes of auditory evoked
      potentials. Although displaying a grossly normal behavior, Df(h15q13)/+ mice are
      more aggressive following exposure to mild stressors, similar to what is
      described in human deletion carriers. Furthermore, Df(h15q13)/+ mice have
      increased body weight, and a similar increase in body weight was subsequently
      found in a sample of human subjects with 15q13.3 deletion. CONCLUSIONS: The
      Df(h15q13)/+ mouse shows similarities to several alterations related to the
      15q13.3 microdeletion syndrome, epilepsy, and schizophrenia, offering a novel
      tool for addressing the underlying biology of these diseases.

PMID- 24090793
TI  - Two distinct amnesic profiles in behavioral variant frontotemporal dementia.
AB  - BACKGROUND: Whether or not episodic memory deficit is a characteristic of
      behavioral variant frontotemporal dementia (bvFTD) is a crucial question for its
      diagnosis and management. METHODS: We compared the episodic memory performance
      profile of bvFTD patients with healthy control subjects and patients with
      Alzheimer's disease (AD) as defined by clinical and biological criteria. Episodic
      memory was assessed with the Free and Cued Selective Reminding Test, which
      controls for effective encoding and identifies memory storage ability resulting
      from consolidation processing. One hundred thirty-four participants were
      evaluated: 56 patients with typical clinical presentation of AD and
      pathophysiological evidence as defined by cerebrospinal fluid AD biomarker
      profile and/or significant amyloid retention on Pittsburgh Compound B positron
      emission tomography; 56 patients diagnosed with bvFTD with no evidence of AD
      cerebrospinal fluid biomarkers when a profile was available (28/56), including 44
      progressive (bvFTD) and 12 nonprogressive (phenocopies) patients; and 22 control
      subjects with negative amyloid imaging. RESULTS: Memory scores could not
      differentiate bvFTD from AD patients (sensitivity and specificity <50%). Taking
      into account the individual distribution of Free and Cued Selective Reminding
      Test scores, half of bvFTD patients had a deficit of free recall, total (free +
      cued) recall, and delayed recall as severe as AD patients. The other half had
      subnormal scores similar to phenocopies and a delayed recall score similar to
      control subjects. CONCLUSIONS: We observed two distinct amnesic profiles in bvFTD
      patients that could reflect two types of hippocampal structure and Papez circuit
      involvement. These findings on episodic memory profiles could contribute to
      discussions on the recent international consensus criteria for bvFTD.

PMID- 24090795
TI  - Do neuronal autoantibodies cause psychosis? A neuroimmunological perspective.
AB  - In the last decade, autoantibodies targeting proteins on the neuronal surface and
      that are believed to be directly pathogenic have been described in patients with
      autoimmune encephalitis. Since then, new antigenic targets have been discovered,
      and new clinical phenotypes have been recognized. The psychotic disorders are one
      example of this expanding spectrum. Here, we consider the defining criteria of
      antibody-mediated central nervous system disease and the extent to which the
      psychiatric data currently satisfy those criteria. We discuss the implications
      these findings have for our understanding, nosology, and treatment of psychiatric
      disorders. 

PMID- 24090794
TI  - Sex differences in sensitivity to the depressive-like effects of the kappa opioid
      receptor agonist U-50488 in rats.
AB  - BACKGROUND: Dynorphin, an endogenous ligand at kappa opioid receptors (KORs),
      produces depressive-like effects and contributes to addictive behavior in male
      nonhuman primates and rodents. Although comorbidity of depression and addiction
      is greater in women than men, the role of KORs in female motivated behavior is
      unknown. METHODS: In adult Sprague-Dawley rats, we used intracranial self
      stimulation to measure effects of the KOR agonist (+/-)-trans-U-50488
      methanesulfonate salt (U-50488) (.0-10.0 mg/kg) on brain stimulation reward in
      gonadally intact and castrated males and in females at estrous cycle stages
      associated with low and high estrogen levels. Pharmacokinetic studies of U-50488
      in plasma and brain were conducted. Immunohistochemistry was used to identify sex
      dependent expression of U-50488-induced c-Fos in brain. RESULTS: U-50488 dose
      dependently increased the frequency of stimulation (threshold) required to
      maintain intracranial self-stimulation responding in male and female rats, a
      depressive-like effect. However, females were significantly less sensitive than
      males to the threshold-increasing effects of U-50488, independent of estrous
      cycle stage in females or gonadectomy in males. Although initial plasma
      concentrations of U-50488 were higher in females, there were no sex differences
      in brain concentrations. Sex differences in U-50488-induced c-Fos activation were
      observed in corticotropin releasing factor-containing neurons of the
      paraventricular nucleus of the hypothalamus and primarily in non-corticotropin
      releasing factor-containing neurons of the bed nucleus of the stria terminalis.
      CONCLUSIONS: These data suggest that the role of KORs in motivated behavior of
      rats is sex-dependent, which has important ramifications for the study and
      treatment of mood-related disorders, including depression and drug addiction in
      people.

PMID- 24090796
TI  - Aberrant disgust responses and immune reactivity in cocaine-dependent men.
AB  - BACKGROUND: Infectious diseases are the most common and cost-intensive health
      complications associated with drug addiction. There is wide belief that drug
      dependent individuals expose themselves more regularly to disease-related
      pathogens through risky behaviors such as sharing pipes and needles, thereby
      increasing their risk for contracting an infectious disease. However, evidence is
      emerging indicating that not only lifestyle but also the immunomodulatory effects
      of addictive drugs, such as cocaine, may account for their high infection risk.
      As feelings of disgust are thought to be an important psychological mechanism in
      avoiding the exposure to pathogens, we sought to investigate behavioral,
      physiological, and immune responses to disgust-evoking cues in both cocaine
      dependent and healthy men. METHODS: All participants (N = 61) were exposed to
      neutral and disgust-evoking photographs depicting food and nonfood images while
      response accuracy, latency, and skin conductivity were recorded. Saliva samples
      were collected before and after exposure to neutral and disgusting images,
      respectively. Attitudes toward disgust and hygiene behaviors were assessed using
      questionnaire measures. RESULTS: Response times to disgust-evoking photographs
      were prolonged in all participants, and specifically in cocaine-dependent
      individuals. While viewing the disgusting images, cocaine-dependent individuals
      exhibited aberrant skin conductivity and increased the secretion of the salivary
      cytokine interleukin-6 relative to control participants. CONCLUSION: Our data
      provide evidence of a hypersensitivity to disgusting stimuli in cocaine-dependent
      individuals, possibly reflecting conditioned responses to noningestive sources of
      infection. Coupled with a lack of interoception of bodily signals, aberrant
      disgust responses might lead to increased infection susceptibility in affected
      individuals.

PMID- 24090798
TI  - Topical combination of diclofenac, calcipotriol, and difluoromethylornithine has
      beneficial effects comparable to 5-fluorouracil for the treatment of non-melanoma
      skin cancer in mice.
AB  - Non-melanoma skin cancer (NMSC) is the most common form of skin cancer. Owing to
      the significant adverse effects of existing treatments, alternatives are needed.
      The aim of this study was to evaluate the use of topically administered
      combination therapy and 5-flurouracil (5-FU) for the treatment of UVB induced
      NMSC in a mouse model. Ninety-six SKH-1 mice were randomized to one placebo group
      and two treatment groups (diclofenac+calcitriol+difluoromethylornithine (DFMO)
      and 5-FU). After UVB radiation for 20 weeks, the mice with tumours were treated
      topically for the following 17 weeks. Both treatments significantly reduced the
      number of tumours, number of mice with tumours as well as tumour area size
      compared with placebo. As the clinical use of 5-FU may induce more adverse
      effects, a combination of diclofenac+calcitriol+DFMO could be a promising
      alternative. Human studies are warranted to determine the beneficial effects and
      possible adverse effects of this new treatment. 

PMID- 24090797
TI  - Widespread reductions in cortical thickness following severe early-life
      deprivation: a neurodevelopmental pathway to attention-deficit/hyperactivity
      disorder.
AB  - BACKGROUND: Children exposed to early-life psychosocial deprivation associated
      with institutional rearing are at markedly elevated risk of developing attention
      deficit/hyperactivity disorder (ADHD). Neurodevelopmental mechanisms that explain
      the high prevalence of ADHD in children exposed to institutionalization are
      unknown. We examined whether abnormalities in cortical thickness and subcortical
      volume were mechanisms explaining elevations in ADHD among children raised in
      institutional settings. METHODS: Data were drawn from the Bucharest Early
      Intervention Project, a cohort of children raised from early infancy in
      institutions in Romania (n = 58) and age-matched community control subjects (n =
      22). Magnetic resonance imaging data were acquired when children were aged 8 to
      10 years, and ADHD symptoms were assessed using the Health and Behavior
      Questionnaire. RESULTS: Children reared in institutions exhibited widespread
      reductions in cortical thickness across prefrontal, parietal, and temporal
      regions relative to community control subjects. No group differences were found
      in the volume of subcortical structures. Reduced thickness across numerous
      cortical areas was associated with higher levels of ADHD symptoms. Cortical
      thickness in lateral orbitofrontal cortex, insula, inferior parietal cortex,
      precuneus, superior temporal cortex, and lingual gyrus mediated the association
      of institutionalization with inattention and impulsivity; additionally,
      supramarginal gyrus thickness mediated the association with inattention and
      fusiform gyrus thickness mediated the association with impulsivity. CONCLUSIONS:
      Severe early-life deprivation disrupts cortical development resulting in reduced
      thickness in regions with atypical function during attention tasks in children
      with ADHD, including the inferior parietal cortex, precuneus, and superior
      temporal cortex. These reductions in thickness are a neurodevelopmental mechanism
      explaining elevated ADHD symptoms in children exposed to institutional rearing.

PMID- 24090799
TI  - Sarcoidosis.
AB  - Sarcoidosis is a systemic disease of unknown cause that is characterised by the
      formation of immune granulomas in various organs, mainly the lungs and the
      lymphatic system. Studies show that sarcoidosis might be the result of an
      exaggerated granulomatous reaction after exposure to unidentified antigens in
      individuals who are genetically susceptible. Several new insights have been made,
      particularly with regards to the diagnosis and care of some important
      manifestations of sarcoidosis. The indications for endobronchial ultrasound in
      diagnosis and for PET in the assessment of inflammatory activity are now better
      specified. Recognition of unexplained persistent disabling symptoms, fatigue,
      small-fibre neurological impairment, cognitive failure, and changes to health
      state and quality of life, has improved. Mortality in patients with sarcoidosis
      is higher than that of the general population, mainly due to pulmonary fibrosis.
      Predicted advances for the future are finding the cause of sarcoidosis, and the
      elucidation of relevant biomarkers, reliable endpoints, and new efficient
      treatments, particularly in patients with refractory sarcoidosis, lung fibrosis,
      and those with persistent disabling symptoms. 

PMID- 24090800
TI  - Influences of hemodilution and anticoagulation on antiplatelet P2Y12 therapy: in
      vitro whole blood perfusion model.

PMID- 24090801
TI  - Pneumothorax after pacemaker implantation: a diagnostic value of sonography.

PMID- 24090802
TI  - Effects of body surface area-indexed calculations in the morbidly obese: a
      mathematical analysis.
AB  - OBJECTIVE: Cardiac and stroke indices routinely are used to communicate the
      adequacy of circulation, especially by cardiac anesthesiologists. However,
      indexed values may be distorted when derived using conventional formulae on
      morbidly obese patients. In extreme cases, distortion of the raw value by the
      indexed value may suggest inappropriate therapeutic interventions. This study
      attempted to highlight threshold values of body surface area (BSA) that place
      morbidly obese patients at risk of being overtreated. DESIGN: Mathematical
      analysis. PARTICIPANTS: Simulated patients. INTERVENTIONS: BSA was derived using
      the commonly used Mosteller and Dubois and Dubois formulae on a range of
      simulated patients. These simulated BSAs then were applied to normal cardiac
      output (CO) and stroke volume (SV) values to identify the threshold at which BSA
      indexed values result in a change in classification to abnormal. Additionally,
      the effects of 7 different published BSA formulae were examined, using a range of
      height-weight combinations. MEASUREMENTS AND MAIN RESULTS: Critical thresholds at
      which BSA calculations would classify normal CO and SV as abnormal are presented
      in a tabular form. Among the 7 BSA formulae, there was substantial variation in
      predicted BSA at a given height-weight combination when values typically
      associated with morbid obesity are used. CONCLUSION: In morbidly obese patients,
      cardiac and stroke indices can be misleading relative to the underlying raw
      values (CO and SV) as a result of distortion by widely used BSA formulae. The
      authors caution against relying on threshold cardiac and stroke indices as
      triggers for the initiation of hemodynamic therapies in the morbidly obese.
      Further research on what BSA formula should be used on patients with very extreme
      body types is warranted.

PMID- 24090803
TI  - The effects of high thoracic epidural anesthesia on sympathetic activity and
      apoptosis in experimentally induced congestive heart failure.
AB  - OBJECTIVE: To evaluate the effect of high thoracic epidural analgesia (HTEA) in
      congestive heart failure (CHF). DESIGN: Rat model of CHF. SETTING: Harbin Medical
      University, Harbin, Heilongjiang, China. PARTICIPANTS: One hundred thirty-five
      rats. INTERVENTIONS: HTEA involved 5 times daily injections of 0.1% lidocaine at
      the T3-T4 level. MEASUREMENTS AND MAIN RESULTS: The authors examined myocardial
      norepinephrine (NE), angiotensin II (Ang II), endothelin-1 (ET1), and tumor
      necrosis factor-alpha (TNF-alpha) concentrations 2, 4, and 6 weeks after the
      start of HTEA. They also examined histologic changes in heart tissue and
      myocardial expression of apoptosis-inducing factor (AIF) and poly (ADP-ribose)
      polymerase (PARP). Sham rats were used as a control. In the time course,
      myocardial NE, Ang II, ET1, and TNF-alpha concentrations were significantly
      higher in the CHF group compared with the HTEA and sham groups (p< 0.05).
      Similarly, PARP and AIF protein expression levels were significantly higher in
      the CHF group compared with the HTEA and sham groups (p< 0.05). Microscopy
      revealed pronounced damage to myocardial cell structures in the CHF group; this
      damage clearly was reduced in the HTEA group. In addition, cardiac function
      evaluation indicated treatment with HTEA resulted in similar heart function as
      animals that did not have surgically induced CHF. CONCLUSIONS: The findings
      suggest that HTEA induces changes in sympathetic nervous system, renin
      angiotensin system, endothelial, and inflammatory process activity involved in
      CHF.

PMID- 24090804
TI  - Cervical fluorosis: a lurking peril.

PMID- 24090805
TI  - Prostaglandin E1 increases the blood flow rate of saphenous vein grafts in
      patients undergoing off-pump coronary artery bypass grafting.
AB  - OBJECTIVE: To compare the effects of prostaglandin E1 (PGEl) versus placebo on
      blood flow rate in coronary artery bypass grafts. DESIGN: A prospective,
      randomized, double-blinded study. SETTING: A teaching hospital. PARTICIPANTS:
      Forty-six patients with stable angina scheduled for isolated elective OPCAB were
      recruited and randomized into group PGE1 and group placebo. INTERVENTION:
      Following randomization, the patients in the PGE1 group (Group PGE1, n = 23)
      received a continuous intravenous infusion of PGEl (10 ng/kg/min) after
      endotracheal intubation and the placebo group (Group placebo, n = 23) received
      the same volume of normal saline. The infusion administration was removed after
      leaving the intensive care unit. MEASUREMENTS AND MAIN RESULTS: The grafts' blood
      flow rate was measured with a transit time flowmeter at 10 minutes and 30 minutes
      after coronary artery grafting. The hemodynamic parameters, including mean
      arterial pressure (MAP), heart rate, and SvO2, VO2I, DO2I, ERO2 monitored by a
      pulmonary artery catheter, were recorded. The blood flow of the saphenous vein
      grafts was significantly higher in the PGE1 group than the placebo group at both
      10 and 30 minutes after coronary artery grafting. At the 10-minute mark, the
      graft flow was 54.9 +/- 31.4 mL/min versus 47.3 +/- 24.6 mL/min in venous
      nonsequential grafts to the left coronary artery for group PGE1 and placebo (p =
      0.000). Corresponding values at 30 minutes were 60.1 +/- 27.8 mL/min versus 48.4
      +/- 26.3 mL/min (p = 0.002). In the venous non-sequential grafts to the right
      coronary artery, a tendency of blood flow also was found to be higher in the PGE1
      group than in the placebo group at 10-minutes (52.7 +/- 29.4 mL/min versus 49.3
      +/- 23.8 mL/min, p = 0.048) and the 30-minutes (58.6 +/- 26.5 mL/min, 50.9 +/-
      25.9 mL/min, p = 0.037). The blood flow rate of the left internal mammary artery
      (LIMA) grafts in group PGE1 was higher than that in the placebo group but did not
      reach statistical significance. The VO2I, DO2I, and ERO2 in the 2 groups at the 2
      time points did not reach statistical significance. The cardiac index (CI) in
      group PGE1 was higher than that of the placebo group at T3 and T4 (p = 0.035 and
      p = 0.012, respectively). The lactate (LAC) at the end of the operation (T2), 4
      hours after the operation (T3), and 24 hours after operation (T4) in the placebo
      group were higher than that of group PGE1 (p = 0.023, p = 0.015, and p = 0.043,
      respectively). The oxygenation saturation of the mixed venous blood (SvO2) in the
      2 groups was decreased but without significant difference. CONCLUSION: PGE1
      significantly increased the flow rate in anastomosed saphenous vein grafts, and
      its beneficial effects on hemodynamics and oxygen metabolism were observed.

PMID- 24090806
TI  - Plasmodium vivax malaria complicated by splenic infarct.
AB  - An 11-year-old girl presented with Plasmodium vivax malaria complicated by shock
      and acute renal failure. The diagnosis of malaria was based on demonstration of
      trophozoites of P. vivax in the peripheral blood smear and a positive rapid
      malarial antigen test for P. vivax but negative for P. falciparum. She responded
      to parenteral artesunate and supportive care. During the course of her infection,
      she developed pain in her left hypochondrium. Ultrasonography showed multiple
      hypo-echoic lesions in the spleen and CT scan revealed multiple splenic infarcts.
      Management was restricted to close clinical monitoring and analgesia. We consider
      that this is the first report of splenic infarct complicating the course of
      childhood P. vivax malaria in the English literature. Physicians should suspect
      and investigate for this rare complication if a patient with malaria complains of
      left upper quadrant abdominal pain, pleuritic left lower chest pain and/or
      enlarging tender splenomegaly during the course of malaria infection. 

PMID- 24090807
TI  - Peri-operative third party red blood cell transfusion in renal transplantation
      and the risk of antibody-mediated rejection and graft loss.
AB  - Historic red blood cell transfusion (RBCT) may induce anti-HLA antibody which, if
      donor specific (DSA), is associated with increased antibody-mediated rejection
      (AMR). Whether post-operative RBCT influences this risk is unknown. We examined
      the RBCT history in 258 renal transplant recipients stratified according to
      prevalent recipient HLA antibody (DSA, Non-DSA or No Antibody). AMR occurred more
      frequently in patients who received RBCT both pre and post transplant compared
      with all other groups (Pre+Post-RBCT 21%, Pre-RBCT 4%, Post-RBCT 6%, No-RBCT 6%,
      HR 4.1 p=0.004). In the 63 patients who received Pre+Post-RBCT, 65% (13/20) with
      DSA developed AMR compared with 0/6 in the Non-DSA group and 2/37 (5%) in the No
      Antibody group (HR 13.9 p<0.001). In patients who received No-RBCT, Pre-RBCT or
      Post-RBCT there was no difference in AMR between patients with DSA, Non-DSA or No
      Antibody. Graft loss was independently associated with Pre+Post-RBCT (HR 6.5,
      p=0.001) AMR (HR 23.9 p<0.001) and Non-AMR (6.0 p=0.003) after adjusting for DSA
      and delayed graft function. Re-exposure to RBCT at the time of transplant is
      associated with increased AMR only in patients with preformed DSA, suggesting
      that RBCT provides additional allostimulation. Patients receiving Pre+Post-RBCT
      also had an increased risk of graft loss independently of AMR or DSA. Both pre
      and post procedural RBCT in renal transplantation is associated with modification
      of immunological risk and warrants additional study. 

PMID- 24090808
TI  - Sodium hypochlorite dental accidents.
AB  - Sodium hypochlorite is widely used in dentistry as an intra-canal irrigant, for
      debridement and to disinfect root canals. Although it is considered to be safe,
      serious mishap can result from its inappropriate use, and this has been reported
      infrequently in the literature. Two unusual cases of sodium hypochlorite toxicity
      and their successful non-surgical management are described in a 14-year-old girl
      and a 13-year-old boy. 

PMID- 24090809
TI  - CJY, an isoflavone, interacts with ATPase of P-glycoprotein in the rat brain
      microvessel endothelial cells (RBMECs).
AB  - Our previous study reported CJY, an isoflavone, can reverse P-glycoprotein (P-gp)
      efflux activity in rat brain microvessel endothelial cells (RBMECs). In the
      present report, by assessment of ATPase activity of RBMECs, we gained further
      insight into the nature of the CJY interactions with P-gp. The results revealed
      that the basal P-gp ATPase activity was increased by CJY. Kinetic studies on
      ATPase activity showed the effects of Tetrandrine (Tet) on CJY-stimulated, CsA on
      CJY-stimulated, and CsA on Tet-stimulated P-gp ATPase activity were all non
      competitive inhibition, indicating that these substrates can simultaneously but
      independently bind to diverse sites on P-gp. Furthermore, the combined effects of
      CJY with Tet, and CJY with CsA were also evaluated isobolographically. The
      results showed synergistic interactions in both combinations, implying that
      combined treatment of CJY with other modulators may exert synergistic
      interactions for the drug's penetration into the brain and the treatment of
      neurological disorders. 

PMID- 24090810
TI  - Catalytic conversion of carbohydrates into 5-hydroxymethylfurfural over cellulose
      derived carbonaceous catalyst in ionic liquid.
AB  - Three environmental-benign and low-cost carbon-based solid acid catalysts
      containing -SO3H, -COOH and phenolic -OH groups were prepared and used for the
      conversion of glucose into 5-hydroxymethylfurfural (HMF) in ionic liquid 1-butyl
      3-methylimidazolium chloride ([BMIM]Cl). The results demonstrated that cellulose
      derived carbonaceous catalyst (CCC) possessed the highest catalytic activity,
      which resulted in 46.4% HMF yield at 160 degrees C for only 15 min. In addition,
      the reaction kinetics for the conversion of glucose into HMF over CCC was fitted
      with the first-order rate equation. The slightly-deactivated CCC after four
      successive reaction runs could be easily regenerated by a simple carbonization
      and sulfonation process. More gratifyingly, the combination of CCC and [BMIM]Cl
      were confirmed to be suitable for converting other carbohydrates such as
      fructose, sucrose, maltose, cellobiose, starch and cellulose into HMF.
      Particularly, a plausible mechanism involving hydrolysis, isomerization and
      dehydration for the conversion of carbohydrates into HMF was also proposed.

PMID- 24090811
TI  - Proteomic approach for identification of immunogenic proteins of Mycoplasma
      mycoides subsp. capri.
AB  - In this study, an immunoproteomic approach was used to identify immunodominant
      proteins from Mycoplasma mycoides subsp. capri isolates. Membrane proteins,
      extracted through TX-114 phase partitioning, were separated using mono- and two
      dimensional electrophoresis and detected by Western blotting with pooled sera
      from naturally infected goats. A total of 27 immunoreactive spots, corresponding
      to 13 different proteins, were identified using nanoLC-ESI-MSMS. Function
      annotation revealed that most of these proteins were metabolic enzymes involved
      in carbohydrate and energy metabolism. The immunogenic proteins identified in
      this study: pyruvate dehydrogenase, dihydrolipoamide acetyltransferase,
      dihydrolipoyl dehydrogenase, phosphate acetyltransferase, phosphopyruvate
      hydratase, adenine phopshoribosyltransferase, transketolase, translation
      elongation factor G, translation elongation factor Ts, FMN-dependent NADH
      azoreductase, peptide methionine sulfoxide reductase, inorganic diphosphatase and
      trigger factor may be used as biomarkers for the serological diagnosis of
      contagious agalactia caused by M. mycoides subsp. capri. 

PMID- 24090812
TI  - Outer membrane vesicles reflect environmental cues in Gallibacterium anatis.
AB  - The Gram-negative bacterium Gallibacterium anatis is a major cause of salpingitis
      and peritonitis in egg-laying chickens, leading to decreased egg-production
      worldwide. Increased knowledge of the pathogenesis and virulence factors is
      important to better understand and prevent the negative effects of G. anatis. To
      this end outer membrane vesicles (OMVs) are natural secretion products of Gram
      negative bacteria, displaying an enormous functional diversity and promising
      results as vaccine candidates. This is the first study to report that G. anatis
      secretes OMVs during in vitro growth. By use of transmission electron microscopy
      (TEM) and SDS-PAGE, we showed that changes in in vitro growth conditions,
      including incubation time, media composition and temperature, affected the OMV
      production and protein composition. A large protein band was increased in its
      concentration after prolonged growth. Analysis by LC-MS/MS indicated that the
      band contained two proteins; the 320.1 kDa FHA precursor, FhaB, and a 407.8 kDa
      protein containing a von Willebrand factor type A (vWA) domain. Additional two
      major outer-membrane (OM) proteins could be identified in all samples; the OmpH
      homolog, OmpC, and OmpA. To understand the OMV formation better, a tolR deletion
      mutation (DeltatolR) was generated in G. anatis. This resulted in a constantly
      high and growth-phase independent production of OMVs, suggesting that depletion
      of peptidoglycan linkages plays a role in the OMV formation in G. anatis. In
      conclusion, our results show that G. anatis produce OMVs in vitro and the OMV
      protein profile suggests that the production is an important and well-regulated
      ability employed by the bacteria, which may be used for vaccine production
      purposes.

PMID- 24090813
TI  - Retrospective analysis of docetaxel, oxaliplatin plus fluorouracil compared with
      epirubicin, cisplatin and fluorouracil as first-line therapy for advanced gastric
      cancer.
AB  - The purpose of this retrospective study was to evaluate the safety and efficacy
      of docetaxel, oxaliplatin plus fluorouracil (DOF) regimen in comparison with
      epirubicin, cisplatin and fluorouracil (ECF) regimen in treating AGC. A total of
      88 AGC patients were treated with DOF regimen (N = 45) and ECF regimen (N = 43)
      respectively. The end points of this study were response rate, survival, and
      toxicity. The overall response rates for DOF and ECF were 42.2% and 37.3%, and
      the respective tumour control rates were 80% and 60.6%, respectively. While the
      median progression-free survival (PFS) approached 6.7 and 5.0 months for DOF and
      ECF, the overall survival (OS) was 11.4 and 9.8 months respectively. Although
      both groups showed acceptable level of toxicity, compared with ECF, DOF group was
      associated with less nausea/vomiting and alopecia but more peripheral neuropathy
      and neutropenia. Although DOF and ECF exhibit similar efficacy, DOF may broaden
      the spectrum of chemotherapeutically treatable patients and deserve further
      investigation. 

PMID- 24090815
TI  - Mode of action of ethyl tertiary-butyl ether hepatotumorigenicity in the rat:
      evidence for a role of oxidative stress via activation of CAR, PXR and PPAR
      signaling pathways.
AB  - To elucidate possible mode of action (MOA) and human relevance of
      hepatotumorigenicity in rats for ethyl tertiary-butyl ether (ETBE), male F344
      rats were administered ETBE at doses of 0, 150 and 1000 mg/kg body weight twice a
      day by gavage for 1 and 2 weeks. For comparison, non-genotoxic carcinogen
      phenobarbital (PB) was applied at a dose of 500 ppm in diet. Significant increase
      of P450 total content and hydroxyl radical levels by low, high doses of ETBE and
      PB treatments at weeks 1 and 2, and 8-OHdG formation at week 2, accompanied
      accumulation of CYP2B1/2B2, CYP3A1/3A2 and CYP2C6, and downregulation of DNA
      oxoguanine glycosylase 1, induction of apoptosis and cell cycle arrest in
      hepatocytes, respectively. Up-regulation of CYP2E1 and CYP1A1 at weeks 1 and 2,
      and peroxisome proliferation at week 2 were found in high dose ETBE group.
      Results of proteome analysis predicted activation of upstream regulators of gene
      expression altered by ETBE including constitutive androstane receptor (CAR),
      pregnane-X-receptor (PXR) and peroxisome proliferator-activated receptors
      (PPARs). These results indicate that the MOA of ETBE hepatotumorigenicity in rats
      may be related to induction of oxidative stress, 8-OHdG formation, subsequent
      cell cycle arrest, and apoptosis, suggesting regenerative cell proliferation
      after week 2, predominantly via activation of CAR and PXR nuclear receptors by a
      mechanism similar to that of PB, and differentially by activation of PPARs. The
      MOA for ETBE hepatotumorigenicity in rats is unlikely to be relevant to humans.

PMID- 24090814
TI  - Carbon monoxide inhalation increases microparticles causing vascular and CNS
      dysfunction.
AB  - We hypothesized that circulating microparticles (MPs) play a role in pro
      inflammatory effects associated with carbon monoxide (CO) inhalation. Mice
      exposed for 1h to 100 ppm CO or more exhibit increases in circulating MPs derived
      from a variety of vascular cells as well as neutrophil activation. Tissue injury
      was quantified as 2000 kDa dextran leakage from vessels and as neutrophil
      sequestration in the brain and skeletal muscle; and central nervous system nerve
      dysfunction was documented as broadening of the neurohypophysial action potential
      (AP). Indices of injury occurred following exposures to 1000 ppm for 1h or to
      1000 ppm for 40 min followed by 3000 ppm for 20 min. MPs were implicated in
      causing injuries because infusing the surfactant MP lytic agent, polyethylene
      glycol telomere B (PEGtB) abrogated elevations in MPs, vascular leak, neutrophil
      sequestration and AP prolongation. These manifestations of tissue injury also did
      not occur in mice lacking myeloperoxidase. Vascular leakage and AP prolongation
      were produced in naive mice infused with MPs that had been obtained from CO
      poisoned mice, but this did not occur with MPs obtained from control mice. We
      conclude that CO poisoning triggers elevations of MPs that activate neutrophils
      which subsequently cause tissue injuries.

PMID- 24090816
TI  - A novel QSAR model of Salmonella mutagenicity and its application in the safety
      assessment of drug impurities.
AB  - As indicated in ICH M7 draft guidance, in silico predictive tools including
      statistically-based QSARs and expert analysis may be used as a computational
      assessment for bacterial mutagenicity for the qualification of impurities in
      pharmaceuticals. To address this need, we developed and validated a QSAR model to
      predict Salmonella t. mutagenicity (Ames assay outcome) of pharmaceutical
      impurities using Prous Institute's Symmetry(SM), a new in silico solution for
      drug discovery and toxicity screening, and the Mold2 molecular descriptor package
      (FDA/NCTR). Data was sourced from public benchmark databases with known Ames
      assay mutagenicity outcomes for 7300 chemicals (57% mutagens). Of these data, 90%
      was used to train the model and the remaining 10% was set aside as a holdout set
      for validation. The model's applicability to drug impurities was tested using a
      FDA/CDER database of 951 structures, of which 94% were found within the model's
      applicability domain. The predictive performance of the model is acceptable for
      supporting regulatory decision-making with 84+/-1% sensitivity, 81+/-1%
      specificity, 83+/-1% concordance and 79+/-1% negative predictivity based on
      internal cross-validation, while the holdout dataset yielded 83% sensitivity, 77%
      specificity, 80% concordance and 78% negative predictivity. Given the importance
      of having confidence in negative predictions, an additional external validation
      of the model was also carried out, using marketed drugs known to be Ames
      negative, and obtained 98% coverage and 81% specificity. Additionally, Ames
      mutagenicity data from FDA/CFSAN was used to create another data set of 1535
      chemicals for external validation of the model, yielding 98% coverage, 73%
      sensitivity, 86% specificity, 81% concordance and 84% negative predictivity.

PMID- 24090817
TI  - A rat retinal damage model predicts for potential clinical visual disturbances
      induced by Hsp90 inhibitors.
AB  - In human trials certain heat shock protein 90 (Hsp90) inhibitors, including 17
      DMAG and NVP-AUY922, have caused visual disorders indicative of retinal
      dysfunction; others such as 17-AAG and ganetespib have not. To understand these
      safety profile differences we evaluated histopathological changes and exposure
      profiles of four Hsp90 inhibitors, with or without clinical reports of adverse
      ocular effects, using a rat retinal model. Retinal morphology, Hsp70 expression
      (a surrogate marker of Hsp90 inhibition), apoptotic induction and pharmacokinetic
      drug exposure analysis were examined in rats treated with the ansamycins 17-DMAG
      and 17-AAG, or with the second-generation compounds NVP-AUY922 and ganetespib.
      Both 17-DMAG and NVP-AUY922 induced strong yet restricted retinal Hsp70 up
      regulation and promoted marked photoreceptor cell death 24h after the final dose.
      In contrast, neither 17-AAG nor ganetespib elicited photoreceptor injury. When
      the relationship between drug distribution and photoreceptor degeneration was
      examined, 17-DMAG and NVP-AUY922 showed substantial retinal accumulation, with
      high retina/plasma (R/P) ratios and slow elimination rates, such that 51% of 17
      DMAG and 65% of NVP-AUY922 present at 30 min post-injection were retained in the
      retina 6h post-dose. For 17-AAG and ganetespib, retinal elimination was rapid
      (90% and 70% of drugs eliminated from the retina at 6h, respectively) which
      correlated with lower R/P ratios. These findings indicate that prolonged
      inhibition of Hsp90 activity in the eye results in photoreceptor cell death.
      Moreover, the results suggest that the retina/plasma exposure ratio and retinal
      elimination rate profiles of Hsp90 inhibitors, irrespective of their chemical
      class, may predict for ocular toxicity potential.

PMID- 24090818
TI  - A validation study of a multiplex INDEL assay for forensic use in four Chinese
      populations.
AB  - Insertion/deletion (INDELs) marker sets can serve as a useful supplementary tool
      for human identification. A commercial kit, the Qiagen DIPplex((r)) Investigator
      kit, multiplexes 30 biallelic autosomal INDELs and Amelogenin for forensic use.
      We performed a validation study based on the DIPplex((r)) kit in four Chinese
      populations: Han, Tibetan, Uyghur, and Kazakh. There were no significant
      departures from Hardy-Weinberg equilibrium or significant linkage disequilibrium
      (pair-wised r(2)<0.2) between the 30 INDELs. The random match probabilities were
      in the range of 3.84 * 10(-11) to 1.20 * 10(-12), and the power of exclusion was
      >0.99. The multiplex PCR was optimized for a 5-MUL volume, full profiles were
      obtained with 0.062 ng/MUL of template DNA, and excellent performance was
      obtained with degraded casework samples. This study demonstrates that the
      multiplex INDEL assay can be used as a supplementary method for degraded DNA
      detection in the studied Chinese populations.

PMID- 24090819
TI  - Impaired self-referential processing in mesial temporal lobe epilepsy: a
      functional MRI study.
AB  - Mesial temporal lobe epilepsy (mTLE) presents typical symptoms of cognitive
      impairments and mental disorders, which is presumed to be related to impairment
      of self-referential processing. This study aims to investigate the alterations of
      self-reference in mTLE using functional magnetic resonance imaging (fMRI). Fifty
      patients with unilateral mTLE (26 left- and 24 right-sided mTLE) were recruited
      in the present study. Traditional task paradigm of internally-cued condition vs.
      externally-cued condition was employed to induce self-referential activation.
      FMRI activation in each group of patients was compared with that of 30 healthy
      controls. Moreover, fMRI responses in the dorsal mesial prefrontal cortex were
      specifically addressed by correlating with behavioral data of reaction times and
      clinical data of epilepsy duration, respectively. Compared with the healthy
      controls, both two groups of patients showed decreased behavioral performance
      (reaction times) and decreased fMRI activation of self-reference in the anterior
      and posterior cortical midline structures. Moreover, fMRI activation was found to
      be negatively correlated with behavioral performance and epilepsy duration. The
      present findings implicate functional impairment of self-reference caused by
      epilepsy in mTLE. This study provided imaging evidence for functional impairments
      of self-referential processing and brain default-mode function in mTLE. 

PMID- 24090820
TI  - alpha-Iso-cubebene exerts neuroprotective effects in amyloid beta stimulated
      microglia activation.
AB  - Schisandra chinensis is commonly used for food and as a traditional remedy for
      the treatment of neuronal disorders. However, it is unclear which component of S.
      chinensis is responsible for its neuropharmacological effects. To answer this
      question, we isolated alpha-iso-cubebene, a dibenzocyclooctadiene lignin, from S.
      chinensis and determined if it has any anti-neuroinflammatory and neuroprotective
      properties against amyloid beta-induced neuroinflammation in microglia. Microglia
      that are stimulated by amyloid beta increased their production of pro
      inflammatory cytokines and chemokines, prostaglandin E2 (PGE2), nitric oxide (NO)
      and reactive oxygen species (ROS) and the enzymatic activity of matrix
      metalloproteinase 9 (MMP-9). We found this was all inhibited by alpha-iso
      cubebene. Consistent with these results, alpha-iso-cubebene inhibited the
      expression of inducible nitric oxide synthase (iNOS), cyclooxygenase 2 (COX-2)
      and MMP-9 in amyloid beta-stimulated microglia. Subsequent mechanistic studies
      revealed that alpha-iso-cubebene inhibited the phosphorylation and degradation of
      IkappaB-alpha, the phosphorylation and transactivity of NF-kappaB, and the
      phosphorylation of MAPK in amyloid beta-stimulated microglia. These results
      suggest that alpha-iso-cubebene impairs the amyloid beta-induced
      neuroinflammatory response of microglia by inhibiting the NF-kappaB and MAPK
      signaling pathways. Importantly, alpha-iso-cubebene can provide critical
      neuroprotection for primary cortical neurons against amyloid beta-stimulated
      microglia-mediated neurotoxicity. To the best of our knowledge, this is the first
      report showing that alpha-iso-cubebene can provide neuroprotection against, and
      influence neuroinflammation triggered by, amyloid beta activation of microglia. 

PMID- 24090821
TI  - Design and baseline data from the Management of Sadness and Anxiety in Cardiology
      (MOSAIC) randomized controlled trial.
AB  - BACKGROUND: Depression and anxiety in cardiac patients are independently
      associated with adverse cardiovascular outcomes, including mortality.
      Collaborative care (CC) programs, which use care managers to assess patients,
      coordinate care, and perform therapeutic interventions, have proven effective in
      managing depression in this population. However, no prior CC intervention has
      simultaneously managed depression and anxiety disorders, and there has been
      minimal study of CC in high-risk cardiac inpatients. MATERIALS AND METHODS: The
      Management of Sadness and Anxiety in Cardiology (MOSAIC) study was a prospective
      randomized trial of a low-intensity CC intervention, compared to enhanced usual
      care, for patients hospitalized for acute coronary syndrome, heart failure, or
      arrhythmia, and diagnosed with depression, generalized anxiety disorder (GAD), or
      panic disorder (PD). The primary outcome measure for MOSAIC was mental health
      related quality of life (HRQoL), measured using the Medical Outcomes Study Short
      Form-12. Additional outcomes included psychological, functional, and medical
      outcomes, including rehospitalizations. RESULTS: A total of 183 eligible
      participants were enrolled (92 collaborative care, 91 enhanced usual care); 94%
      of depressed patients reported being depressed for >1month, and 53% of those with
      GAD reported clinically significant anxiety for >1year. One hundred thirty-three
      patients had depression, 118 had GAD, and 19 had PD; 74 participants (40%) had
      two or more of the disorders. CONCLUSION: The MOSAIC trial will provide data
      regarding whether an intervention that concurrently manages these common
      psychiatric disorders results in meaningful improvements in HRQoL, psychiatric
      symptoms, and medical outcomes in cardiac patients at high risk for adverse
      outcomes.

PMID- 24090822
TI  - Towards improved animal models for evaluating social cognition and its disruption
      in schizophrenia: the CNTRICS initiative.
AB  - Social cognition refers to processes used to monitor and interpret social signals
      from others, to decipher their state of mind, emotional status and intentions,
      and select appropriate social behaviour. Social cognition is sophisticated in
      humans, being embedded with verbal language and enacted in a complex cultural
      environment. Its disruption characterises the entire course of schizophrenia and
      is correlated with poor functional outcome. Further, deficits in social cognition
      are related to impairment in other cognitive domains, positive symptoms (paranoia
      and delusions) and negative symptoms (social withdrawal and reduced motivation).
      In light of the significance and inadequate management of social cognition
      deficits, there is a need for translatable experimental procedures for their
      study, and identification of effective pharmacotherapy. No single paradigm
      captures the multi-dimensional nature of social cognition, and procedures for
      assessing ability to infer mental states are not well-developed for experimental
      therapeutic settings. Accordingly, a recent CNTRICS meeting prioritised
      procedures for measuring a specific construct: "acquisition and recognition of
      affective (emotional) states", coupled to individual recognition. Two
      complementary paradigms for refinement were identified: social
      recognition/preference in rodents, and visual tracking of social scenes in non
      human primates (NHPs). Social recognition is disrupted in genetic, developmental
      or pharmacological disease models for schizophrenia, and performance in both
      procedures is improved by the neuropeptide oxytocin. The present article surveys
      a broad range of procedures for studying social cognition in rodents and NHPs,
      discusses advantages and drawbacks, and focuses on development of social
      recognition/preference and gaze-following paradigms for improved study of social
      cognition deficits in schizophrenia and their potential treatment. 

PMID- 24090823
TI  - Harnessing cognitive neuroscience to develop new treatments for improving
      cognition in schizophrenia: CNTRICS selected cognitive paradigms for animal
      models.
AB  - Over the past two decades, the awareness of the disabling and treatment
      refractory effects of impaired cognition in schizophrenia has increased
      dramatically. In response to this still unmet need in the treatment of
      schizophrenia, the Cognitive Neuroscience Treatment Research to Improve Cognition
      in Schizophrenia (CNTRICS) initiative was developed. The goal of CNTRICS is to
      harness cognitive neuroscience to develop a brain-based set of tools for
      measuring cognition in schizophrenia and to test new treatments. CNTRICS meetings
      focused on development of tasks with cognitive construct validity for use in both
      human and animal model studies. This special issue presents papers discussing the
      cognitive testing paradigms selected by CNTRICS for animal model systems. These
      paradigms are designed to measure cognitive constructs within the domains of
      perception, attention, executive function, working memory, object/relational long
      term memory, and social/affective processes. 

PMID- 24090824
TI  - Anterior decompressive surgery after cervical laminoplasty in patients with
      ossification of the posterior longitudinal ligament.
AB  - BACKGROUND CONTEXT: Two surgical procedures, posterior decompressive surgery
      (PDS) and anterior decompressive surgery (ADS), are the treatment options for
      cervical ossification of the posterior longitudinal ligament (OPLL). Each
      procedure has advantages and disadvantages. Cervical laminoplasty, a type of PDS,
      is relatively easy to perform and can be used for patients with multilevel cord
      compression. ADS can often be more technically demanding. OBJECTIVE: The purpose
      of this study was to clarify the clinical characteristics and surgical results of
      the patients for whom ADS was necessary after PDS. STUDY DESIGN: Retrospective
      study. METHODS: A total of 144 patients, followed for more than 3 years after
      cervical laminoplasty, were included. The neurologic status was graded using the
      Japanese Orthopedic Association (JOA score). Eleven patients underwent ADS after
      PDS. The clinical background and surgical outcomes were evaluated. Radiological
      findings of the 11 patients requiring ADS after PDS (PA group) and the 133 PDS
      patients not requiring ADS (P group) were compared. RESULTS: In the PA group, the
      JOA score was slightly deteriorated during follow-up after cervical laminoplasty.
      Severe pain in the unilateral upper extremity and deterioration of cervical
      myelopathy were the most typical symptoms necessitating ADS. The incidence of the
      mixed type of OPLL was significantly higher in this group. The JOA score improved
      in all patients after ADS as a second surgery. CONCLUSIONS: In our strategy for
      the surgical treatment of cervical OPLL, PDS with laminoplasty remains as the
      initial treatment, and in patients with neurological deterioration and newly
      developed clinical symptoms during follow-up, ADS is considered as a salvage
      procedure.

PMID- 24090825
TI  - Effects of noxious stimulation and pain expectations on neuromuscular control of
      the spine in patients with chronic low back pain.
AB  - BACKGROUND CONTEXT: Alterations of the neuromuscular control of the lumbar spine
      have been reported in patients with chronic low back pain (LBP). During trunk
      flexion and extension tasks, the reduced myoelectric activity of the low back
      extensor musculature observed during full trunk flexion is typically absent in
      patients with chronic LBP. PURPOSE: To determine whether pain expectations could
      modulate neuromuscular responses to experimental LBP to a higher extent in
      patients with chronic LBP compared with controls. STUDY DESIGN: A cross
      sectional, case-control study. PATIENT SAMPLE: Twenty-two patients with
      nonspecific chronic LBP and 22 age- and sex-matched control participants.
      METHODS: Trunk flexion-extension tasks were performed under three experimental
      conditions: innocuous heat, noxious stimulation with low pain expectation, and
      noxious stimulation with high pain expectation. Noxious stimulations were
      delivered using a contact heat thermode applied on the skin of the lumbar region
      (L4-L5), whereas low or high pain expectations were induced by verbal and visual
      instructions. OUTCOME MEASURES: Surface electromyography of erector spinae at L2
      L3 and L4-L5, as well as lumbopelvic kinematic variables were collected during
      the tasks. Pain was evaluated using a numerical rating scale. Pain
      catastrophizing, disability, anxiety, and fear-avoidance beliefs were measured
      using validated questionnaires. RESULTS: Two-way mixed analysis of variance
      revealed that pain was significantly different among the three experimental
      conditions (F2,84=317.5; p<.001). Increased myoelectric activity of the low back
      extensor musculature during full trunk flexion was observed in the high compared
      with low pain expectations condition at the L2-L3 level (F2,84=9.5; p<.001) and
      at the L4-L5 level (F2,84=3.7; p=.030). At the L4-L5 level, this effect was
      significantly more pronounced for the control participants compared with patients
      with chronic LBP (F2,84=3.4; p=.045). Pearson correlation analysis revealed that
      increased lumbar muscle activity in full flexion induced by expectations was
      associated with higher pain catastrophizing in patients with chronic LBP (r=0.54;
      p=.012). CONCLUSIONS: Repeated exposure to pain appears to generate rigid and
      less variable patterns of muscle activation in patients with chronic LBP, which
      attenuate their response to pain expectations. Patients with high levels of pain
      catastrophizing show higher myoelectric activity of lumbar muscles in full
      flexion and exhibit greater neuromechanical changes when expecting strong pain.

PMID- 24090826
TI  - Clinical suspicion of bilateral carotid body paraganglioma and an unexpected
      histologic diagnosis.
AB  - Carotid body tumor (CBT) is the most common of the head and neck paragangliomas
      (PGLs). Conversely, synovial sarcomas are usually located around knee and ankle
      joint and rare variants occur in the oral cavity. A 68-year-old man presented
      with a left voluminous painless cervical mass. The diagnosis of CBT of type III
      Shamblin was suspected. The cervical mass was removed en bloc. Unexpectedly,
      pathologic examination showed monophasic synovial sarcoma. Excision of PGLs
      remains the therapy of choice, especially to make a correct histologic diagnosis.

PMID- 24090827
TI  - Multicenter audit of emergency endovascular repair of infrarenal aortic
      aneurysms.
AB  - BACKGROUND: Emergency endovascular aneurysm repair (eEVAR) for infrarenal
      abdominal aortic aneurysm has become widely accepted as an alternative to open
      repair, if the aortic anatomy is favorable and endovascular expertise is readily
      available. The aim of this study is to report the outcome of eEVAR in Hong Kong.
      METHODS: This was a retrospective review of prospectively collected data from
      Hong Kong Hospital Authority Clinical Data Analysis and Reporting System (CDARS),
      Clinical Management System (CMS), and departmental prospective computerized
      databases. Patient demographics, clinical and biochemical parameters,
      perioperative complications, and outcomes were recorded and analyzed. The
      independent sample t-test was used for continuous variables and the Fisher's
      exact test was used for nonparametric variables. Kaplan-Meier analysis was
      performed for overall survival and survival of subgroups. Binary logistic
      regression was performed for factors predicting perioperative mortality. SPSS
      software (version 15.0; SPSS Inc., Chicago, IL) was used for all statistical
      analyses. RESULTS: A total of 40 patients (36 men with a mean age of 74.9 +/-
      1.53 years [range: 52-89 years]) underwent emergency eEVAR between January 2006
      and September 2011 in 6 Hospital Authority Hospitals in Hong Kong. All patients
      were treated using commercially available aortoiliac endografts (including 26
      bifurcated and 14 aorto-uniiliac grafts). There was 1 conversion from eEVAR to
      open repair. Blood loss, operating time, duration of stay in intensive care, and
      duration of stay in the hospital were 948 +/- 495.5 mL, 194 +/- 12.7 min, 4.7 +/-
      1.26 days, and 14.5 +/- 2.19 days, respectively. The 7-day, 30-day, and 12-month
      mortality rates were 15%, 17.5%, and 35%, respectively. Six patients required
      reintervention on follow-up, and 8 patients died during hospitalization. Cox
      regression analysis of survival found that hypotension (P = 0.001) and being >76
      years of age (P = 0.002) were associated with reduced overall survival. Binary
      logistic regression found that hypotension is associated with increased 30-day
      mortality (P = 0.026). CONCLUSIONS: This audit shows that the results of eEVAR in
      Hong Kong are comparable to international standards. In the endovascular era,
      this may be an attractive alternative to emergency open aneurysm repair.

PMID- 24090828
TI  - Mandibular subluxation as an adjunct in very distal carotid arterial
      reconstruction: incidence of peripheral and cerebral neurologic sequelae in a
      single-center experience.
AB  - BACKGROUND: The location of the carotid bifurcation and a very distal extension
      of internal carotid atherosclerotic disease may challenge vascular surgeons
      performing carotid endarterectomy (CEA) by increasing technical difficulty and
      possibly the incidence of cranial nerve damage or palsies. The objective of the
      present study is to report on the safety of CEA with mandibular subluxation (MS)
      and to compare results of CEA in 2 groups of patients treated by standard CEA or
      by MS-CEA according to rates of major neurologic complications, death, and the
      occurrence of postoperative peripheral nerve palsy. METHODS: Between July 2000
      and June 2012, 1,357 CEAs were performed. MS was additionally used in 43
      patients. Only patients with primary atherosclerotic internal carotid artery
      (ICA) lesions in the 2 groups (38 in the MS-CEA group and 1,289 in the standard
      CEA group) were considered for comparative analysis. RESULTS: MS-CEA patients
      were more frequently male (P = 0.03), presented more frequently with symptomatic
      lesions (P = 0.007), longer lesions (P = 0.01), and had common ICA bypass
      implantation (P = 0.02). Mean follow-up was 68.75 +/- 37.87 months (range: 1-144
      months). No perioperative neurologic mortality and no prolonged discomfort
      related to MS was recorded. The overall neurologic morbidity rate (major
      stroke/minor stroke/transient ischemic attach) was comparable in the 2 groups (P
      = 0.78). The overall immediate peripheral nerve injury rate was 7.89% in the MS
      CEA group and 5.27% in the standard CEA group (P = 0.73). Three cases of
      permanent dysphonia in the standard CEA group (0.23%) and 1 case of dysphagia in
      the MS-CEA group (2.63%) were reported at follow-up (P = 0.24). CONCLUSIONS: MS
      CEA can be a very useful technical adjunct for high-located carotid bifurcations
      or challenging carotid lesions, with an overall risk comparable to that of
      standard CEA.

PMID- 24090829
TI  - Effect of anticoagulation and antiplatelet therapy on incidence of endoleaks and
      sac size expansions after endovascular aneurysm repair.
AB  - BACKGROUND: The effects of anticoagulation or antiplatelet therapy on the
      incidence of endoleak and aneurysm sac size after endovascular aneurysm repair
      (EVAR) are unclear. This study aims to determine whether these therapies affect
      the incidence of endoleaks or sac size expansions after EVAR. METHODS: The case
      notes of 407 patients (367 men and 40 women, mean age 74.7 years) who underwent
      elective EVAR between January 2006 and November 2011 were reviewed for medication
      history and EVAR-related outcomes. RESULTS: The median follow-up period was 18
      months. There were 45 (11.1%) patients on warfarin (WA), 292 (71.7%) on
      antiplatelet therapy (AT) (aspirin, clopidogrel, or dipyridamole modified
      release), and 70 (17.2%) on no anticoagulation or antiplatelet therapy (NA).
      During the study period, 51 (12.5%) endoleaks were documented, 8 type I (AT = 6,
      NA = 0, and WA = 2) and 42 type II (AT = 31, NA = 9, and WA = 2). Medication did
      not significantly affect the incidence of type I (P = 0.24) (based on chi-squared
      analysis), type II (P = 0.33), or type III (P = 0.82) endoleaks, or sac
      expansions (P = 0.95). CONCLUSIONS: Warfarin and antiplatelet therapies are not
      associated with increased incidence of postoperative endoleaks or aneurysm sac
      expansion after EVAR. The data in this study support safe use of anticoagulant
      and antiplatelet medications in patients undergoing EVAR.

PMID- 24090830
TI  - Polybrominated diphenyl ethers in e-waste: level and transfer in a typical e
      waste recycling site in Shanghai, Eastern China.
AB  - Very few data for polybrominated diphenyl ethers (PBDEs) were available in the
      electronic waste (e-waste) as one of the most PBDEs emission source. This study
      reported concentrations of PBDEs in e-waste including printer, rice cooker,
      computer monitor, TV, electric iron and water dispenser, as well as dust from e
      waste, e-waste dismantling workshop and surface soil from inside and outside of
      an e-waste recycling plant in Shanghai, Eastern China. The results showed that
      PBDEs were detected in the majority of e-waste, and the concentrations of
      SigmaPBDEs ranged from not detected to 175 g/kg, with a mean value of 10.8 g/kg.
      PBDEs were found in TVs made in China after 1990. The mean concentrations of
      SigmaPBDEs in e-waste made in Korea, Japan, Singapore and China were 1.84 g/kg,
      20.5 g/kg, 0.91 g/kg, 4.48 g/kg, respectively. The levels of SigmaPBDEs in e
      waste made in Japan far exceed the threshold limit of RoHS (1.00 g/kg). BDE-209
      dominated in e-waste, accounting for over 93%. The compositional patterns of
      PBDEs congeners resembled the profile of Saytex 102E, indicating the source of
      deca-BDE. Among the samples of dust and surface soil from a typical e-waste
      recycling site, the highest concentrations of Sigma18PBDEs and BDE-209 were found
      in dust in e-waste, ranging from 1960 to 340,710 ng/g and from 910 to 320,400
      ng/g, which were 1-2 orders of magnitude higher than other samples. It suggested
      that PBDEs released from e-waste via dust, and then transferred to surrounding
      environment.

PMID- 24090831
TI  - Ultrasound-assisted extraction of D-pinitol from carob pods using Response
      Surface Methodology.
AB  - This study reports on the optimization of the conditions of extraction of D
      pinitol compound from carob pods by using ultrasonication. For this purpose, the
      Box-Behnken design, which is a widely used form of Response Surface Methodology,
      was used to investigate the effects of parameters on the ultrasound-assisted
      extraction. Four independent variables, temperature ( degrees C), ultrasonic
      power (W), dilution rate (material:water ratio) and time (min), were studied. The
      results showed that the highest D-pinitol concentration of 11.98 g/L was obtained
      with an extraction temperature of 50  degrees C, ultrasonic power of 207 W, a
      dilution rate of 1:4 and an extraction time of 120 min. It was found that the D
      pinitol concentration of carob extract increased with the effect of
      ultrasonication during the extraction process. Therefore, ultrasound-assisted
      extraction could be used as an alternative to conventional hot water extraction
      with respect to the recovery of D-pinitol from carob pods with the advantages of
      lower extraction temperatures, shorter extraction time and reduced energy
      consumption.

PMID- 24090832
TI  - Sonochemical synthesis, structural, magnetic and grain size dependent electrical
      properties of NdVO4 nanoparticles.
AB  - NdVO4 nanoparticles are successfully synthesized by efficient sonochemical method
      using two different structural directing agents like CTAB and P123. The phase
      formation and functional group analysis are carried out using X-ray diffraction
      (XRD) and fourier transform infra red (FT-IR) spectra, respectively. Using
      Scherrer equation the calculated grain sizes are 27 nm, 24 nm and 20 nm
      corresponding to NdVO4 synthesized by without surfactant, with CTAB and P123,
      respectively. The TEM images revealed that the shape of NdVO4 particles is rice
      like and rod shaped particles while using CTAB and P123 as surfactants. The
      growth mechanism of NdVO4 nanoparticles is elucidated with the aid of TEM
      analysis. From electrical analysis, the conductivity of NdVO4 nanoparticles
      synthesized without surfactant showed a higher conductivity of 5.5703 * 10(-6) S
      cm(-1). The conductivity of the material depends on grain size and increased with
      increase in grain size due to the grain size effect. The magnetic measurements
      indicated the paramagnetic behavior of NdVO4 nanoparticles.

PMID- 24090833
TI  - Ultrasound-assisted extraction of phenolics from wine lees: modeling,
      optimization and stability of extracts during storage.
AB  - The ultrasound-assisted extraction process of phenolics including anthocyanins
      from wine lees was modeled and optimized in this research. An ultrasound bath
      system with the frequency of 40 kHz was used and the acoustic energy density
      during extraction was identified to 48 W/L. The effects of extraction time,
      extraction temperature, solvent-to-solid ratio and the solvent composition on the
      extraction yields of total phenolics and total anthocyanins were taken into
      account. The extraction process was simulated and optimized by means of
      artificial neural network (ANN) and genetic algorithm (GA). The constructed ANN
      models were accurate to predict the extraction yields of both total phenolics and
      total anthocyanins according to the statistical analysis. Meanwhile, the input
      space of the ANN models was optimized by GA, so as to maximize the extraction
      yields. Under the optimal conditions, the experimental yields of total phenolics
      and total anthocyanins were 58.76 and 6.69 mg/g, respectively, which agreed with
      the predicted values. Furthermore, more amounts of total phenolics and total
      anthocyanins were extracted by ultrasound at the optimal conditions than by
      conventional maceration. On the other hand, the stability of phenolics in the
      liquid extracts obtained from ultrasound-assisted extraction during storage was
      evaluated. After 30-day storage, the total phenolic contents in extracts stored
      at 4  degrees C and 20  degrees C decreased by 12.5% and 12.1%, respectively.
      Moreover, anthocyanins were more stable at 4  degrees C while tartaric esters and
      flavonols exhibited a better stability at 20  degrees C. Overall, the loss of
      phenolics during storage found in this study could be acceptable.

PMID- 24090835
TI  - Block copolymer mixtures as antimicrobial hydrogels for biofilm eradication.
AB  - Current antimicrobial strategies have mostly been developed to manage infections
      due to planktonic cells. However, microbes in their nature state will tend to
      exist by attaching to and growing on living and inanimate surfaces that result in
      the formation of biofilms. Conventional therapies for treating biofilm-related
      infections are likely to be insufficient due to the lower susceptibility of
      microbes that are embedded in the biofilm matrix. In this study, we report the
      development of biodegradable hydrogels from vitamin E-functionalized
      polycarbonates for antimicrobial applications. These hydrogels were formed by
      incorporating positively-charged polycarbonates containing propyl and benzyl side
      chains with vitamin E moiety into physically cross-linked networks of "ABA"-type
      polycarbonate and poly(ethylene glycol) triblock copolymers. Investigations of
      the mechanical properties of the hydrogels showed that the G' values ranged from
      1400 to 1600 Pa and the presence of cationic polycarbonate did not affect the
      stiffness of the hydrogels. Shear-thinning behavior was observed as the hydrogels
      displayed high viscosity at low shear rates that dramatically decreased as the
      shear rate increased. In vitro antimicrobial studies revealed that the more
      hydrophobic VE/BnCl(1:30)-loaded hydrogels generally exhibited better
      antimicrobial/antifungal effects compared to the VE/PrBr(1:30) counterpart as
      lower minimum biocidal concentrations (MBC) were observed in Staphylococcus
      aureus (Gram-positive), Escherichia coli (Gram-negative) and Candida albicans
      (fungus) (156.2, 312.5, 312.5 mg/L for VE/BnCl(1:30) and 312.5, 2500 and 625 mg/L
      for VE/PrBr(1:30) respectively). Similar trends were observed for the treatment
      of biofilms where VE/BnCl(1:30)-loaded hydrogels displayed better efficiency with
      regards to eradication of biomass and reduction of microbe viability of the
      biofilms. Furthermore, a high degree of synergistic antimicrobial effects was
      also observed through the co-delivery of antimicrobial polycarbonates with a
      conventionally-used antifungal agent, fluconazole. These hydrogels also displayed
      excellent compatibility with human dermal fibroblasts with cell viability >80%
      after treatment with hydrogels loaded with cationic polymers and/or fluconazole
      at minimum biocidal concentrations (MBC).

PMID- 24090834
TI  - A dual sensor for real-time monitoring of glucose and oxygen.
AB  - A dual glucose and oxygen sensor in a polymer format was developed. The dual
      sensor composed of a blue emitter as the glucose probe, a red emitter as an
      oxygen probe, and a yellow emitter as a built-in reference probe which does not
      respond to either glucose or oxygen. All the three probes were chemically
      immobilized in a polyacrylamide-based matrix. Therefore, the dual sensor
      possesses three well separated emission colors and ratiometric approach is
      applicable for analysis of the glucose and oxygen concentration at biological
      conditions. The sensor was applied for real-time monitoring of glucose and oxygen
      consumption of bacterial cells, Escherichia coli (E. coli) and Bacillus subtilis
      (B. subtilis), and mammalian cells of mouse macrophage J774 and human cervical
      cancer HeLa cell lines. On the other hand, in order to achieve satisfactory
      sensing performance for glucose, compositions of the matrices among poly(2
      hydroxyethyl methacrylate), polyacrylamide, and poly(6-aminohexyl methacrylamide)
      which is a linker polymer for grafting the glucose probe, were optimized.

PMID- 24090836
TI  - Cetuximab conjugated vitamin E TPGS micelles for targeted delivery of docetaxel
      for treatment of triple negative breast cancers.
AB  - We developed a system of Cetuximab-conjugated micelles of vitamin E TPGS for
      targeted delivery of docetaxel as a model anticancer drug for treatment of the
      triple negative breast cancer (TNBC), which shows no expression of either one of
      the hormone progesterone receptor (PR), estrogen receptor (ER) and epidermal
      growth factor receptor 2 (HER2) and is thus more difficult to be treated than the
      positive breast cancer. Such micelles are of desired particle size, drug loading,
      drug encapsulation efficiency and drug release profile. Their surface morphology,
      surface charge and surface chemistry were also characterized. The fibroblast
      cells (NIH3T3), HER2 overexpressed breast cancer cells (SK-BR-3), ER and PR
      overexpressed breast cancer cells (MCF7), and TNBC cells of high, moderate and
      low EGFR expression (MDA MB 468, MDA MB 231 and HCC38) were employed to access in
      vitro cellular uptake of the coumarin 6 loaded TPGS micelles and cytotoxicity of
      docetaxel formulated in the micelles. The high IC50 value, which is the drug
      concentration needed to kill 50% of the cells in a designated period such as 24
      h, obtained from Taxotere((r)) showed that the TNBC cells are indeed more
      resistant to the free drug than the positive breast cancer cells. However, the
      therapeutic effects of docetaxel could be greatly enhanced by the formulation of
      Cetuximab conjugated TPGS micelles, which demonstrated 205.6 and 223.8 fold
      higher efficiency than Taxotere((r)) for the MDA MB 468 and MDA MB 231 cell lines
      respectively.

PMID- 24090837
TI  - A mechanical microconnector system for restoration of tissue continuity and long
      term drug application into the injured spinal cord.
AB  - Complete transection of the spinal cord leaves a gap of several mm which fills
      with fibrous scar tissue. Several approaches in rodent models have used tubes,
      foams, matrices or tissue implants to bridge this gap. Here, we describe a
      mechanical microconnector system (mMS) to re-adjust the retracted spinal cord
      stumps. The mMS is a multi-channel system of polymethylmethacrylate (PMMA),
      designed to fit into the spinal cord tissue gap after transection, with an outlet
      tubing system to apply negative pressure to the mMS thus sucking the spinal cord
      stumps into the honeycomb-structured holes. The stumps adhere to the
      microstructure of the mMS walls and remain in the mMS after removal of the
      vacuum. We show that the mMS preserves tissue integrity and allows axonal
      regrowth at 2, 5 and 19 weeks post lesion with no adverse tissue effects like in
      bleeding or cyst formation. Preliminary assessment of locomotor function in the
      open field suggested beneficial effects of the mMS. Additional inner micro
      channels enable local substance delivery into the lesion center via an attached
      osmotic minipump. We suggest that the mMS is a suitable device to adapt and
      stabilize the injured spinal cord after surgical resection of scar tissue (e.g.,
      for chronic patients) or traumatic injuries with large tissue and bone damages.

PMID- 24090838
TI  - Bioconjugated nanoparticles for attachment and penetration into pathogenic
      bacteria.
AB  - As an antimicrobial agent, silver nanoparticles functionalized with both
      bacitracin A and polymyxin E (AgNPs-BA&PE) were designed and synthesized with
      complementary antibacterial functions to act against gram-positive and gram
      negative bacteria. AgNPs-BA&PE could easily get attached and penetrate into the
      bacterial cell membrane through surface-immobilized BA and PE with a membrane
      target, resulting in up to 10-fold increase in the antibacterial activity,
      without the emergence of bacterial resistance. Analysis of the antimicrobial
      mechanism confirmed that the synthesized nanoparticles caused disorganization of
      the bacterial cytomembrane and leakage of cytoplasmic contents. This
      antimicrobial agent with better biocompatibility can promote healing of infected
      wounds, and has promising and useful applications in biomedical devices and
      antibacterial control systems.

PMID- 24090839
TI  - The safety profile of a cationic lipid-mediated cystic fibrosis gene transfer
      agent following repeated monthly aerosol administration to sheep.
AB  - Clinically effective gene therapy for Cystic Fibrosis has been a goal for over 20
      years. A plasmid vector (pGM169) that generates persistent expression and reduced
      host inflammatory responses in mice has raised prospects for translation to the
      clinic. The UK CF Gene Therapy Consortium is currently evaluating long-term
      repeated delivery of pGM169 complexed with the cationic lipid GL67A in a large
      Multidose Trial. This regulatory-compliant evaluation of aerosol administration
      of nine doses of pGM169/GL67A at monthly intervals, to the sheep lung, was
      performed in preparation for the Multidose Trial. All sheep tolerated treatment
      well with no adverse effects on haematology, serum chemistry, lung function or
      histopathology. Acute responses were observed in relation to bronchoalveolar
      cellularity comprising increased neutrophils and macrophage numbers 1 day post
      delivery but these increases were transient and returned to baseline. Importantly
      there was no cumulative inflammatory effect or lung remodelling with successive
      doses. Molecular analysis confirmed delivery of pGM169 DNA to the airways and
      pGM169-specific mRNA was detected in bronchial brushing samples at day 1
      following doses 1, 5 and 9. In conclusion, nine doses of pGM169/GL67A were well
      tolerated with no significant evidence of toxicity that would preclude adoption
      of a similar strategy in CF patients.

PMID- 24090840
TI  - Effect of zinc oxide nanomaterials-induced oxidative stress on the p53 pathway.
AB  - Excessive production of reactive oxygen species (ROS) is a hallmark feature in
      nanomaterials (NMs) induced cellular toxicity. However, the inter-relationship
      between NMs induced ROS generation and the cells innate ability to regulate
      intracellular ROS level in effecting a particular cellular outcome is currently
      underexplored. Here, using a BJ fibroblast p53 knockdown system, we showed that
      p53 may be implicated in playing a dual regulatory role to determine cell
      survivability in response to oxidative stress induced by ZnO NMs. At low level of
      ZnO NMs induced ROS, p53 triggers expression of antioxidant genes such as SOD2,
      GPX1, SESN1, SESN2 and ALDH4A1 to restore oxidative homeostasis while at high
      concentration of ZnO NMs, the elevated level of intracellular ROS activated the
      apoptotic pathway through p53. The implication of our finding that p53 can
      function as an important regulator in determining ZnO induced cytotoxicity is
      highlighted by the differential action of ZnO on p53 deficient and proficient
      colorectal cell lines. p53 deficient cells cancer cells such as DLD-1 and SW480
      are more susceptible to ZnO induced cell death compared to p53 proficient cells
      such as colon epithelial cells NCM460 and HCT116 cells in a ROS dependent manner.
      Collectively, our findings showcased a role p53 plays in the context of
      nanotoxicity and highlights the need to consider the interplay of physicochemical
      properties of NMs and cell biology.

PMID- 24090841
TI  - From 'What the F#@% is a Facebook?' to 'Who Doesn't Use Facebook?': The role of
      criminal lifestyles in the adoption and use of the Internet.
AB  - Concerns about a digital divide persist and recent calls have been made for
      understanding how lifestyles influence Internet adoption and use. Online criminal
      behaviors have drawn attention from law enforcement, but diffusion of innovation
      theory suggests higher propensities for crime, particularly street crime, reduces
      the likelihood of Internet use. Drawing from this theory and research on the role
      of street criminal lifestyles on technology adoption, this study examined
      patterns of Internet use among a sample of 585 individuals at-risk for and
      involved in street crime. Results from our logistic and negative binomial
      regression analyses lead to two general conclusions: (1) compared to research on
      the general population, similar predictors and lower rates of Internet
      participation and usage are observed, and (2) mixed evidence suggests
      participation in criminal lifestyles contributes to digital inequality. The
      results support a theory of technological diffusion to marginalized populations.
      We conclude by discussing the expansion of technology, digital inequality, and
      crime. 

PMID- 24090842
TI  - The impact of respondents and interviewers on interview speed in face-to-face
      interviews.
AB  - In surveys carried out by interviewers trained according to the key principle of
      standardized interviewing it is assumed that the interviewer has only limited
      impact on the time a respondent needs to answer questions. In the paper the
      effects of interviewers and respondent characteristics on interview speed are
      analyzed simultaneously by means of a three-level random coefficient model. Data
      from the fifth round of the European Social Survey (ESS) are used. In twelve
      participating countries (CAPI) timers were implemented at several places in the
      questionnaire. Based on this time information the interview speed (number of
      questions asked per minute) was measured for each respondent during five modules
      of the questionnaire. The results support most of the expectations concerning the
      effects of the respondent characteristics. However, the results also indicate
      that, for all countries, interviewers strongly determine the interview speed and
      that interview length is not a simple linear function of the number of questions
      in a questionnaire. 

PMID- 24090843
TI  - Incomplete equalization: The effect of tracking in secondary education on
      educational inequality.
AB  - This paper tests whether the existence of vocationally oriented tracks within a
      traditionally academically oriented upper education system reduces socioeconomic
      inequalities in educational attainment. Based on a statistical model of
      educational transitions and data on two entire cohorts of Danish youth, we find
      that (1) the vocationally oriented tracks are less socially selective than the
      traditional academic track; (2) attending the vocationally oriented tracks has a
      negative effect on the likelihood of enrolling in higher education; and (3) in
      the aggregate the vocationally oriented tracks improve access to lower-tier
      higher education for low-SES students. These findings point to an interesting
      paradox in that tracking has adverse effects at the micro-level but equalizes
      educational opportunities at the macro-level. We also discuss whether similar
      mechanisms might exist in other educational systems. 

PMID- 24090844
TI  - From general discrimination to segmented inequality: Migration and inequality in
      urban China.
AB  - Internal migration in China during the last three decades, the largest in human
      history, offers a rare opportunity to understand inequalities in the making.
      Using data spanning 10years from China's largest metropolis, Shanghai, this study
      assesses how enduring state institutions interplay with the spread of market
      forces to shape income inequality between migrants and native urban workers.
      Though the wages of both Chinese migrants and urban workers rose considerably,
      economic restructuring during the decade under study resulted in diminished
      privileges for urbanites and subsequently increased collision between migrants
      and urban workers in the private sectors. These shifts, rather than substantially
      reducing inequality, have led to an evolving form of inequality, from an initial
      general blatant discrimination against migrants across the board, to a new and
      more subtle form of inequality characterized by substantial segmented
      discrimination against migrants within economic sectors, with the degree of
      inequality varying from sector to sector. We discuss how this changing inequality
      reflects complementary rather than competing roles of the state and market
      institutions in inequality creation and maintenance. 

PMID- 24090845
TI  - Exchange and cohesion in dyads and triads: A test of Simmel's hypothesis.
AB  - This paper uses social exchange theory to address a classic question posed by
      Simmel (1964) regarding dyads and triads. The question is whether exchanges in a
      triad will generate more cohesion at the group level than exchanges in an
      isolated dyad. The main hypotheses, integrating several ideas from Simmel and
      social exchange theories, are as follows. First, triads generate less variability
      of behavior than dyads; that is, there is more uniformity or convergence in
      triads. Second, in the context of repeated exchange, we predict higher levels of
      cohesion in triads than in dyads. Third, positive emotion or affect has a
      stronger impact on cohesion in dyads than in triads, whereas uncertainty
      reduction has a stronger impact on cohesion in triads. To test these hypotheses,
      an experiment compared isolated dyads to dyads nested in a triadic exchange
      network. Subjects engaged in exchanges across a series of distinct episodes,
      using standard experimental procedures from research on relational cohesion
      (Lawler and Yoon, 1996) and exchange networks (Molm and Cook, 1995; Willer,
      1999). Consistent with the hypotheses, the results reveal more convergence of
      behavior and higher cohesion in triads than in dyads; moreover, uncertainty
      reduction is the primary basis for cohesion in the triad, whereas positive affect
      was the primary basis for cohesion in the dyad. These results are discussed in
      relation to Simmelian dyad-triad dynamics and the theory of relational cohesion. 

PMID- 24090846
TI  - Patterns of change in religious service attendance across the life course:
      Evidence from a 34-year longitudinal study.
AB  - Although a number of studies have uncovered evidence of age differences in
      religious involvement across the life course, there has been a lack of long-term
      longitudinal data to test the extent to which these differences are due to
      changes within individuals over time. This study tracks trajectories of change in
      religious service attendance using data collected longitudinally over the course
      of up to 34years, between 1971 and 2005, and in ages ranging from 15 to 102.
      Piecewise growth curve modeling was used to examine changes in the patterns of
      age-related change in three distinct developmental periods: the transition from
      adolescence to young adulthood, middle adulthood, and older adulthood. Attendance
      showed an average pattern of quadratic decline in adolescence, stability in
      middle adulthood, and a quadratic pattern of more rapid increase followed by
      decrease over the course of older adulthood. These results suggest that
      developmental factors play a role in changing patterns of religious participation
      across the adult life course, and may account for some of the apparent
      differences between age groups. 

PMID- 24090847
TI  - American income inequality across economic and geographic space, 1970-2010.
AB  - This analysis examines the spatial clustering of income inequality and its
      socioeconomic correlates at the meso-scale over the past four decades. Cluster
      analysis is used to group N=3078 counties into five inequality clusters; and
      multinomial logistic regression is used to assess the effects of socioeconomic
      correlates. High and extreme inequality places are concentrated in large
      metropolitan centers, high amenity rural areas, and parts of the Great Plains and
      Mountain West. They tend to have better socioeconomic outcomes, with fewer at
      risk populations, higher incomes, lower poverty, and greater economic
      participation. Unequal places are more specialized in high-skill finance and
      professional services, and in energy-based mining. By contrast, equality places
      are associated with low-skill services, education and health services,
      manufacturing, and stable farm economies. 

PMID- 24090848
TI  - Housework: Cause and consequence of gender ideology?
AB  - Nearly all quantitative studies examining the association between the division of
      housework and gender ideology have found that gender egalitarianism results in
      less housework for wives, more for husbands, and more equal sharing of housework
      by couples. However, a few studies suggest housework has a nontrivial influence
      on gender ideology. An overreliance on single-direction, single-equation
      regression models and cross-sectional data has limited past research from making
      strong claims about the causal relationship between gender ideology and
      housework. We use data on married couples from Waves 1 and 2 of the National
      Survey of Families and Households and nonrecursive simultaneous equation models
      to assess the causal relationship between housework and gender ideology. Results
      show a mutual and reciprocal relationship between the division of housework and
      gender ideology for both husbands' and wives'. Reciprocity is strongest for
      husbands while for wives the relationship is partially indirect and mediated
      through their husbands' gender ideologies. 

PMID- 24090849
TI  - Trends in gender segregation in the choice of science and engineering majors.
AB  - Numerous theories have been put forward for the high and continuing levels of
      gender segregation in science, technology, engineering, and mathematics (STEM)
      fields, but research has not systematically examined the extent to which these
      theories for the gender gap are consistent with actual trends. Using both
      administrative data and four separate longitudinal studies sponsored by the U.S.
      Department of Education's National Center for Education Statistics (NCES), we
      evaluate several prominent explanations for the persisting gender gap in STEM
      fields related to mathematics performance and background and general life goals,
      and find that none of them are empirically satisfactory. Instead, we suggest that
      the structure of majors and their linkages to professional training and careers
      may combine with gender differences in educational goals to influence the
      persisting gender gap in STEM fields. An analysis of gendered career aspirations,
      course-taking patterns, and pathways to medical and law school supports this
      explanation. 

PMID- 24090850
TI  - Are environmental attitudes influenced by survey context? An investigation of the
      context dependency of the New Ecological Paradigm (NEP) Scale.
AB  - General environmental attitudes are often measured with questions added to
      surveys about specific environmental or non-environmental issues. Using results
      from a large-scale national survey on the protection of threatened and endangered
      marine species, we examine whether the context of the survey in which New
      Ecological Paradigm (NEP) Scale items are asked influence measured environmental
      concern. In this application the role that specific threatened or endangered
      species play in affecting responses to NEP Scale items is explored using a
      combination of non-parametric and parametric approaches. The results in this case
      suggest that context does influence stated general environmental attitudes,
      though the effects of context differ across NEP items. 

PMID- 24090851
TI  - Disentangling mode-specific selection and measurement bias in social surveys.
AB  - A large-scale mixed-mode experiment linked to the Dutch Crime Victimization
      Survey was conducted in 2011. The experiment consisted of two waves; one wave
      with random assignment to one of the modes web, paper, telephone and face-to
      face, and one follow-up wave to the full sample with interviewer modes only. The
      objective of the experiment is to estimate total mode effects and more
      specifically the corresponding mode effect components arising from undercoverage,
      nonresponse and measurement. In this paper, mode-specific selection and
      measurement bias are defined, and estimators for the bias terms based on the
      experimental design are introduced and discussed. The proposed estimators are
      applied to a number of key survey variables from the Labour Force Survey and the
      Crime Victimization Survey. 

PMID- 24090852
TI  - Explaining monetary donations to international development organisations: A
      factorial survey approach.
AB  - This article investigates what type of international development organisations
      potential donors would prefer to donate to. We constructed 960 scenarios in which
      a fictive development organisation was described. The scenarios were randomly
      varied across eight characteristics of the organisation: size, familiarity,
      experience, religious character, number of different projects run by the
      organisation, number of countries in which the organisation is active, overhead
      costs and staff composition. A large representative sample of the Dutch
      population (N=2,758) received six randomly allocated scenarios and had to decide
      if, and if so, how much they would donate to the depicted (fictive) organisation.
      Results demonstrate that donors have a preference for familiar organisations with
      several years of experience. Although donors have a strong aversion regarding
      overhead costs, we find that donors seem to value the capacities of paid staff
      members and are, to a certain extent, willing to pay a price for these. The ideal
      development organisation combines features typical of small(er) scale voluntary
      development organisations (e.g. mainly run by volunteers) and large(r) scale
      professional organisations (e.g. running development programmes in numerous
      countries). 

PMID- 24090853
TI  - Assessing the effect of social desirability on nativism attitude responses.
AB  - Attempts to measure and analyze public opinion attitudes toward racial/ethnic
      minorities often confront the "social desirability" problem: those who have
      prejudiced attitudes are rarely willing to admit them to surveyors. Instead, they
      may be more likely to give a socially acceptable answer rather an accurate
      reflection of their views. Previous research has clearly established that this
      effect presents a challenge for accurately measuring self-reported racial and
      policy attitudes that primarily affect African-Americans. It is less clear,
      however, how it might affect self-reported responses to attitudes dealing with
      Latinos and immigration. This study thus seeks to analyze the extent to which
      social desirability may affect survey measures of perceived levels of cultural
      threat (nativism). Results from two separate analyses using the Crowne-Marlowe
      "social desirability scale" and a survey "list experiment" demonstrate that
      social desirability is indeed a concern for accurately measuring nativism in the
      American public, but that it exerts an opposite effect from what has previously
      been observed: nativist attitudes tend to be over-reported in opinion surveys. 

PMID- 24090854
TI  - Psychological distress of marital and cohabitation breakups.
AB  - Using data from a large survey, the British Household Panel Survey (BHPS), this
      paper explores the extent to which marital and cohabiting unions differ with
      respect to the short-term effects of union dissolution on mental health. We
      compare married individuals who divorced or separated with cohabitors whose first
      union ended and test the hypothesis that married individuals experience larger
      negative effects. Results show that initial differences are not statistically
      significant once the presence of children is controlled for, suggesting that the
      presence of children is a particularly significant source of increased
      psychological distress in union dissolutions. However, parenthood does not
      explain serious psychological distress, which appears to be associated with
      enduring traits (the personality trait neuroticism). 

PMID- 24090855
TI  - Personal networks of prisoners prior to incarceration: A comparison with the
      general Dutch population.
AB  - This study examines inmates' core discussion network prior to their
      incarceration. The core discussion network consists of the immediate social
      circle of relatively strong ties. The aims of the study are twofold: (1) to
      describe inmates' core discussion network prior to their incarceration in terms
      of network structure, relationship quality and embedded socioeconomic resources;
      (2) to compare inmates' core discussion network with the core discussion network
      of the general Dutch population. Data are analyzed from the Prison Project
      (n=1909) and the Survey of the Social Networks of the Dutch (n=394). Compared
      with the general Dutch population, prior to incarceration, prisoners generally
      have a core discussion network that is similar to or even better with respect to
      network structure and relationship quality. However, prisoners' core discussion
      network members seem to lack socioeconomic resources. 

PMID- 24090856
TI  - Living life for others and/or oneself: The social development of life
      orientations.
AB  - A range of social science research suggests Americans are becoming more self
      oriented over time, and that this focus comes at a cost to general concern with
      community. Examining data from a large-scale national study of college students,
      we explore this influential hypothesis on two fronts. First, we empirically
      investigate whether people who are especially concerned with personal achievement
      are necessarily less concerned about contributing to their community. Contrary to
      most iterations of the individualism thesis, we find that significant numbers of
      individuals are concerned with both personal success and political/social
      involvement. To explore further, we expand this supposed single dimension into a
      fourfold typology, showing that many people are 'idealists' (concerned with both
      self and others) and 'apathists' (relatively unconcerned with either). After
      broadening the taken-for-granted egoist/altruist continuum, we explore antecedent
      social structural, aspirational, and social psychological factors that predict
      membership in these value preference groups. The findings from our preliminary
      model suggest that these broad orientations are shaped by a complex array of
      factors across multiple domains. 

PMID- 24090857
TI  - Evaluating Effectively Maintained Inequality: School and post-school transitions,
      socioeconomic background, academic ability and curricular placement.
AB  - Effectively Maintained Inequality (EMI) is proposed as an explanation for
      contemporary socioeconomic inequalities in education. Socioeconomic inequalities
      are 'maintained' by students from lower socioeconomic backgrounds taking less
      advantageous curricula influencing their post-school destinations. The purpose of
      this study is to evaluate EMI by addressing several hypotheses derived from the
      EMI thesis using Australian longitudinal data. It analyses within-school
      transitions and the transition from school to post-school destinations (elite
      university, other university, vocational and no post-school study or training).
      The study also models curricular placement (subject choice). It finds that the
      transitions within- and post-school are more powerfully influenced by students'
      academic ability than by socioeconomic background. Furthermore, subject choice
      has strong impacts on the transitions. Similarly, Year 12 subject choice is only
      weakly predicted by socioeconomic background, and more strongly influenced by
      ability and occupational interests. In turn, occupational interests are largely
      independent of socioeconomic background. The EMI thesis is not supported. 

PMID- 24090858
TI  - Classroom sex composition and first-grade school outcomes: The role of classroom
      behavior.
AB  - Using nationally representative data from the Early Childhood Longitudinal Study
      Kindergarten Cohort (N=21,409; 10,452 girls and 10,957 boys; mean age=7.24years),
      the association between first-grade classroom sex composition (CSC), measured as
      the percentage of female students, and end of the year academic (reading,
      mathematics) and socio-emotional (externalizing problems, internalizing problems,
      self-control, interpersonal skills) outcomes was examined. Using multilevel
      modeling techniques and controlling for prior achievement levels, CSC was
      positively associated with children's reading achievement at the end of first
      grade; students performed better in reading in classes with a higher percentage
      of female students. CSC was also associated with three of the socio-emotional
      outcomes; controlling for prior levels, students in classrooms with a higher
      percentage of girls had better self-control and interpersonal skills and fewer
      internalizing problems. Classroom behavior mediated the effects of CSC on reading
      achievement and the socio-emotional outcomes. Implications for the composition of
      first-grade classrooms are discussed. 

PMID- 24090859
TI  - Skin color, sex, and educational attainment in the post-civil rights era.
AB  - We assess the relationship between skin color and educational attainment for
      native-born non-Hispanic Black and White men and women, using data from the
      Coronary Artery Risk Development in Young Adults (CARDIA) Study. CARDIA is a
      medical cohort study with twenty years of social background data and a continuous
      measure of skin color, recorded as the percent of light reflected off skin. For
      Black men and women, we find a one-standard-deviation increase in skin lightness
      to be associated with a quarter-year increase in educational attainment. For
      White women, we find an association approximately equal in magnitude to that
      found for Black respondents, and the pattern of significance across educational
      transitions suggests that skin color for White women is not simply a proxy for
      family background. For White men, any relationship between skin color and
      attainment is not robust and, analyses suggest, might primarily reflect
      differences in family background. Findings suggest that discrimination on the
      basis of skin color may be less specific to race than previously thought. 

PMID- 24090860
TI  - Peer group ties and executive compensation networks.
AB  - Publicly traded firms in the US typically determine C.E.O. compensation by
      benchmarking the pay of their C.E.O.s against the pay of C.E.O.s in "peer" firms.
      Consequently, executive compensation is influenced not only by firm-level
      characteristics, but also by the selection and actions of the firm's immediate
      peers as well as by the structure of the executive compensation network overall.
      Analyzing compensation peer group choices made by the same 1183 firms for F.Y.
      2007, 2008 and 2009, we find that while the typical compensation peer is similar
      in size and industry to the firm that chose it, deviations from this norm are
      common, especially among larger firms, and tend to be towards larger firms with
      better paid CEOs. Further analysis shows that firms who pay CEOs well relative to
      the pay that would be predicted from their revenues, return on assets, and
      industry tend to have greater aspiration bias in their group of named peers. 

PMID- 24090861
TI  - Period effects, cohort effects, and the narrowing gender wage gap.
AB  - Despite the abundance of sociological research on the gender wage gap, questions
      remain. In particular, the role of cohorts is under investigated. Using data from
      the Current Population Survey, we use age-period-cohort analysis to uniquely
      estimate age, period, and cohort effects on the gender wage gap. The narrowing of
      the gender wage gap that occurred between 1975 and 2009 is largely due to cohort
      effects. Since the mid-1990s, the gender wage gap has continued to close absent
      of period effects. While gains in female wages contributed to declines in the
      gender wage gap for cohorts born before 1950, for later cohorts the narrowing of
      the gender wage gap is primarily a result of declines in male wages. 

PMID- 24090863
TI  - Black and white homebuyer, homeowner, and household segregation in the United
      States, 1990-2010.
AB  - As homeownership has been expanding in the United States over the past several
      decades, residential segregation between blacks and whites has been declining in
      most metropolitan areas. However, the degree to which the residential patterns of
      new homebuyers have mirrored these overall trends in segregation and how the
      massive increase in home buying has related to changes in segregation has
      remained largely unexplored. This paper examines the segregation of new black
      homebuyers from white households, new white homebuyers from black households, and
      black and white households from each other using Home Mortgage Disclosure Act
      (HMDA) data from 1992 to 2010 merged with data from the Census and ACS. I find
      that black homebuyers are less segregated from white households than black
      homeowners overall and black households in general, providing evidence in support
      of the spatial assimilation model that would predict better outcomes for
      homeowners. Also consistent with the spatial assimilation perspective, I found in
      the multivariate models that increased income parity between blacks and whites
      and growth in black lending are associated with average declines in black/white
      household segregation from 1990 to 2010. Although subprime lending was not
      associated with overall changes in segregation, metropolitan areas with higher
      percentages of loans to blacks from subprime lenders experienced increases in
      segregation of both black homeowners from white households as well as white
      owners from black households. 

PMID- 24090862
TI  - Housing and neighborhood quality among undocumented Mexican and Central American
      immigrants.
AB  - Extensive research has documented the challenges that undocumented immigrants
      face in navigating U.S. labor markets, but relatively little has explored the
      impact of legal status on residential outcomes despite their widespread
      repercussions for social well-being. Using data from the 1996-2008 panels of the
      Survey of Income and Program Participation to impute documentation status among
      Mexican and Central American immigrants, we examine group differences in
      residential outcomes, including homeownership, housing crowding, satisfaction
      with neighborhood and housing quality, problems with neighborhood crime/safety,
      governmental services, and environmental issues, and deficiencies with housing
      units. Results from our analysis indicate that undocumented householders are far
      less likely to be homeowners than documented migrants, and also live in more
      crowded homes, report greater structural deficiencies with their dwellings, and
      express greater concern about the quality of public services and environmental
      conditions in their neighborhoods. In comparison to native whites, undocumented
      migrants' residential circumstances are lacking, but their residential outcomes
      tend to be superior to those of native-born blacks. Overall, our results
      highlight the pervasive impact of legal status on stratifying Mexicans' and
      Central Americans' prospects for successful incorporation, but also underscore
      the rigidity of the black/nonblack divide structuring American residential
      contexts. 

PMID- 24090864
TI  - One country, three populations: Trust in police among migrants, villagers, and
      urbanites in China.
AB  - While the past decade has witnessed the burgeoning of research on public
      assessments of the police in China, marginalized social groups have rarely been
      considered in this line of inquiry. Using data collected from migrant workers,
      rural villagers, and urban dwellers, this study assesses whether Chinese
      perceptions of the police are distinguishable along procedural-based trust and
      outcome-based trust and whether expressive concerns and instrumental concerns are
      predictive of trust in the police. Findings show that Chinese citizens tend to
      conflate procedural-based trust and outcome-based trust. Expressive concerns play
      a more important role than instrumental concerns, with such expressive variables
      as trust in neighborhood residents committee, perceived law and order, and
      quality of life influencing trust in the police. Public perceptions of police
      trustworthiness are also significantly linked to media influence. Directions for
      future research are discussed. 

PMID- 24090865
TI  - Understanding selection bias, time-lags and measurement bias in secondary data
      sources: Putting the Encyclopedia of Associations database in broader context.
AB  - Secondary data gathered for purposes other than research play an important role
      in the social sciences. A recent data release has made an important source of
      publicly available data on associational interests, the Encyclopedia of
      Associations (EA), readily accessible to scholars (www.policyagendas.org). In
      this paper we introduce these new data and systematically investigate issues of
      lag between events and subsequent reporting in the EA, as these have important
      but under-appreciated effects on time-series statistical models. We further
      analyze the accuracy and coverage of the database in numerous ways. Our study
      serves as a guide to potential users of this database, but we also reflect upon a
      number of issues that should concern all researchers who use secondary data such
      as newspaper records, IRS reports and FBI Uniform Crime Reports. 

PMID- 24090866
TI  - The variability of the large genomic segment of Tahyna orthobunyavirus and an all
      atom exploration of its anti-viral drug resistance.
AB  - Tahyna virus (TAHV), a member of the Bunyaviridae family (California complex), is
      an important but neglected human mosquito-borne pathogen. The virus genome is
      composed of three segments, i.e., small (S), medium (M), and large (L). Previous
      studies on genetic variability of viruses within the California complex were
      focused on S and M segments, but the L segment remains relatively unstudied. To
      assess the genetic variation and the relation to virus phenotype we analyzed the
      L segment sequences of biologically diverse TAHV strains isolated in the Czech
      Republic and Slovakia. Phylogenetic analysis covering all available sequences of
      the L segment of TAHV clearly revealed two distinguished lineages, tentatively
      named as "European" and "Asian". The L segment strains within the European
      lineage are highly conserved (identity 99.3%), whilst Asian strains are more
      genetically diverse (identity 97%). Based on sequence comparison with other
      bunyaviruses, several non-synonymous nucleotide substitutions unique for TAHV in
      the L segment were identified. We also identified specific residue substitutions
      in the endonuclease domain of TAHV compared with the La Crosse virus. Since the
      endonuclease domain of the La Crosse virus has been resolved, we employed an all
      energy landscape algorithm to analyze the ligand migration of a viral polymerase
      inhibitor. This allowed us to demonstrate, at the atomic level, that this viral
      polymerase inhibitor randomly explored the specific residue substitutions in the
      endonuclease domain of the TAHV L segment. 

PMID- 24090867
TI  - Effects of phototherapy using different light sources on oxidant and antioxidant
      status of neonates with jaundice.
AB  - BACKGROUND/AIM: Neonates have limited antioxidant protective capacity. It has
      recently been demonstrated that phototherapy used for treatment of neonatal
      jaundice produces oxidative stress. Various phototherapy devices using different
      light sources are available for phototherapy. We aimed to investigate the effects
      of phototherapy applied with different light sources on the global
      oxidant/antioxidant status in neonates. METHODS: Term and late-preterm (>=35
      weeks) newborn infants hospitalized to receive phototherapy for non-hemolytic
      jaundice in the 2-9 days of life were enrolled. Infants who received conventional
      phototherapy with fluorescent lamps were defined as group 1, intensive light
      emitting diode (LED) phototherapy as group 2, and fiberoptic phototherapy as
      group 3. The serum total antioxidant capacity (TAC) and total oxidant status
      (TOS) were measured before and 24 h after phototherapy. Oxidative stress index
      (OSI) was calculated. RESULTS: Twenty nine patients were included in each group.
      At the beginning of phototherapy serum TAC, TOS and OSI levels were similar in
      all groups. After phototherapy serum TAC decreased significantly in all three
      groups (p < 0.001). Total oxidant status increased significantly in group 1 (p <
      0.001) and group 2 (p = 0.001) whereas a statistically insignificant increase was
      observed in group 3 (p = 0.057). After phototherapy OSI increased significantly
      in group 1 (p < 0.001), group 2 (p = 0.001), and group 3 (p = 0.038). CONCLUSION:
      As indicated by increased OSI, oxidant/antioxidant balance is disturbed in favor
      of oxidants after blue fluorescent light, LED and fiberoptic phototherapy.

PMID- 24090868
TI  - Is maternal obesity associated with sustained inflammation in extremely low
      gestational age newborns?
AB  - BACKGROUND: The offspring of obese women are at increased risk for systemic
      inflammation. Blood concentrations of inflammatory proteins in preterm newborns
      of obese women have not been reported. AIM: To compare blood concentrations in
      the highest quartile for gestational age of inflammatory proteins and day of
      blood specimen collection on two days at least one week apart of newborns of
      overweight (i.e., BMI 25-29) and obese women (i.e., BMI >= 30) with newborns of
      women with lower BMIs. Because deliveries for spontaneous indications are more
      likely than those for other indications to be associated with inflammation, we
      evaluated spontaneous indication deliveries separately from maternal or fetal
      indications. STUDY DESIGN: Prospective cohort study. SUBJECTS AND OUTCOME
      MEASURES: We measured from 939 children born before the 28th week of gestation 25
      inflammation-related proteins in blood obtained on postnatal day 1 (range 1-3),
      day 7 (range 5-8) and day 14 (range 12-15). RESULTS: Among infants delivered for
      spontaneous indications, maternal BMI was not related to elevated concentrations
      of any protein. Among infants delivered for maternal (i.e., preeclampsia) or
      fetal indications, those whose mother was overweight or obese were more likely
      than others to have elevated concentrations of inflammation proteins.
      CONCLUSIONS: Maternal pre-pregnancy overweight and obesity appear to contribute
      to a pro-inflammatory state in very preterm newborns delivered for maternal or
      fetal indications. Our failure to see a similar pattern among newborns delivered
      for spontaneous indications, which often have inflammatory characteristics, might
      reflect competing risks.

PMID- 24090869
TI  - Construction and targeted retrieval of specific clone from a non-gridded soybean
      bacterial artificial chromosome library.
AB  - Although a post-genomic era is emerging for many plants, the bacterial artificial
      chromosome (BAC) library is still a valuable tool for genomic studies and
      preservation of precious genetic resources. Construction of non-gridded BAC
      libraries would dramatically reduce cost and save storage space. A non-gridded
      BAC library composed of approximately 96,000 insert-containing clones in 80 pools
      with an average insert size of 75 kb was constructed. This library represented
      5.2 genome equivalents. We successfully developed a unique procedure to retrieve
      positive clones from the non-gridded pools. With this retrieving protocol, the
      non-gridded library system can be adapted to different species and to serve
      various research needs.

PMID- 24090870
TI  - Design of a multiwalled carbon nanotube-Nafion-cysteamine modified tyrosinase
      biosensor and its adaptation of dopamine determination.
AB  - In this work, a multiwalled carbon nanotube (MWCNT)-Nafion-cysteamine (CA)
      modified tyrosinase biosensor brings a new and original perspective to biosensor
      technology intended for the development of dopamine determination. Dopamine
      measurements were done at 0.2V with the amperometric method by the developed
      biosensor system. In addition, in this study dopamine determination was carried
      out by using the differential pulse voltammetry method between potentials of 0.4
      and -0.15 V. In the optimization studies of the biosensor, some parameters such
      as optimal pH, optimal temperature, optimal enzyme amount, and effect of MWCNT
      concentration were investigated. Afterward, in the characterization studies, some
      parameters such as linearity and reproducibility were determined. In the
      reproducibility experiment, an average value of 1.026 MUM, a standard deviation
      of +/-0.03975, and a coefficient of variation of 3.8% were determined for a 1-MUM
      dopamine concentration (n=15). Determination of dopamine was carried out in drug
      samples by the developed biosensor.

PMID- 24090871
TI  - Determination of glycated hemoglobin with special emphasis on biosensing methods.
AB  - The glycated hemoglobin (HbA1c) level in blood is a measure of long-term glycemic
      status in patients with diabetes mellitus. Current clinical methods for
      determination of the HbA1c level include electrophoresis/electroendosmosis, ion
      exchange chromatography, high-performance liquid chromatography, boronate
      affinity chromatography, immunoassay, and liquid chromatography-tandem mass
      spectroscopy in addition to fluorometry and colorimetry. These methods have
      certain drawbacks such as being complex, time-consuming, and requiring expensive
      apparatus and trained persons to operate. These drawbacks were overcome by
      biosensing methods. We review these biosensors, which are based on (i)
      measurement of electrons, that is, current generated from splitting of hydrogen
      peroxide released during oxidation of fructosyl valine by immobilized fructosyl
      amino acid oxidase, which is directly proportional to HbA1c concentration, and
      (ii) direct measurement of HbA1c by some specific reaction. HbA1c biosensors work
      optimally within 4 to 1800 s, between pH 7.0 and 9.0 and between 25 and 45 
      degrees C, and in the range of 1 to 10,000 MUM, with a detection limit between 20
      and 500 MUM and sensitivity between 4.6 nA and 21.5 MUA mM-1 cm-2 and stable over
      a period of 5 to 90 days. We suggest the ways to modify existing HbA1c
      biosensors, leading to simple, reliable, and economical sensors ideally suited
      for point-of-care treatment.

PMID- 24090872
TI  - Long-term stability of thermophilic co-digestion submerged anaerobic membrane
      reactor encountering high organic loading rate, persistent propionate and
      detectable hydrogen in biogas.
AB  - The performance of thermophilic anaerobic co-digestion of coffee grounds and
      sludge using membrane reactor was investigated for 148 days, out of a total
      research duration of 263 days. The OLR was increased from 2.2 to 33.7 kg
      COD/m(3)d and HRT was shortened from 70 to 7 days. A significant irreversible
      drop in pH confirmed the overload of reactor. Under a moderately high OLR of 23.6
      kg-COD/m(3)d, and with HRT and influent total solids of 10 days and 150 g/L,
      respectively, the COD removal efficiency was 44.5%. Hydrogen in biogas was around
      100-200 ppm, which resulted in the persistent propionate of 1.0-3.2g/L. The VFA
      consumed approximately 60% of the total alkalinity. NH4HCO3 was supplemented to
      maintain alkalinity. The stability of system relied on pH management under steady
      state. The 16SrDNA results showed that hydrogen-utilizing methanogens dominates
      the archaeal community. The propionate-oxidizing bacteria in bacterial community
      was insufficient.

PMID- 24090873
TI  - Safety and regulatory requirements and challenge for CNS drug development.
AB  - As our recognition and understanding of diseases and disorders of the central
      nervous system (CNS) become more insightful, and society's concerns for the
      safety, efficacy, and use of such drugs become more acute, the regulatory
      requirements and expectations around assessing potential safety of the drug have
      continued to become more complex. Currently, these concerns and requirements are
      addressed in a time phased manner, attempting to match the advance of spending
      rate on assessing safety issues in alignment with advancing the moiety through
      development of the therapeutics. This article seeks to communicate all the
      critical but frequently overlooked aspects of current and pending regulatory
      requirements including the lesser known parts associated with impurities, active
      metabolites, and distribution of active components to (and subsequent clearance
      from) the population brain. While there are some exciting developments in
      treating CNS diseases with stem cells and some protein based therapies (Aboody et
      al., 2011), drugs meant to favorably effect, prevent, or cure a disease process
      within the central nervous system (CNS) are primarily small molecule and must
      meet a number of regulatory and scientifically mandated criteria to establish
      that their safety in clinical use is acceptable. This is initially done in in
      vivo animals or in in vitro preparations. The starting place for such nonclinical
      safety assessment requires some fundamental assumptions about the potential
      therapeutic (Ball et al., 2007; Gad, 2009; ICH S6, 2004; ICH M3 (R2), 2008). The
      first assumption is that the primary intended route of therapeutic administration
      is oral, as is indeed the case for the vast majority of both current and for most
      potential new drugs. Most aspects of nonclinical safety assessment do not depend
      on route, and we will consider the situations where the use of other routes
      influences requirements for nonclinical safety assessment, and why. A second
      general case assumption in the usual case is that drug administration frequency
      (or regimen) is once daily, though this assumption is less frequently made (in
      real life) than the oral route assumption. Regulations, costs, and acceptance of
      risks (Enna and Williams, 2009) along with adherence to the phased process of
      clinical drug development have caused the task or flow of performances of
      regulatory nonclinical safety assessment studies to be considered as occurring in
      three sequential parts (once the initial candidate screening and lead selection
      phase are complete). These are the studies (1) done to allow initiation of
      clinical trials, (2) done to allow initiation of clinical trials sufficient to
      support a marketing application, and (3) required to allow a marketing
      application. Employment of new technologies, such as in vivo imaging has aided,
      to both help understand specificity of delivery to target tissue sites and
      mechanisms of both action and undesirable actions. 

PMID- 24090874
TI  - Fabrications of zinc-releasing biocement combining zinc calcium phosphate to
      calcium phosphate cement.
AB  - Recently, zinc-releasing bioceramics have been the focus of much attention owing
      to their bone-forming ability. Thus, some types of zinc-containing calcium
      phosphate (e.g., zinc-doped tricalcium phosphate and zinc-substituted
      hydroxyapatite) are examined and their osteoblastic cell responses determined. In
      this investigation, we studied the effects of zinc calcium phosphate (ZCP)
      derived from zinc phosphate incorporated into calcium phosphate cement (CPC) in
      terms of its setting reaction and MC3T3-E1 osteoblast-like cell responses.
      Compositional analysis by powder X-ray diffraction analysis revealed that HAP
      crystals were precipitated in the CPC containing 10 or 30wt% ZCP after
      successfully hardening. However, the crystal growth observed by scanning electron
      microscopy was delayed in the presence of additional ZCP. These findings indicate
      that the additional zinc inhibits crystal growth and the conversion of CPC to the
      HAP crystals. The proliferation of the cells and alkaline phosphatase (ALP)
      activity were enhanced when 10wt% ZCP was added to CPC. Taken together, ZCP added
      CPC at an appropriate fraction has a potent promotional effect on bone substitute
      biomaterials. 

PMID- 24090875
TI  - Effects of ageing, prolonged estrogen deficiency and zoledronate on bone tissue
      mineral distribution.
AB  - The quantity and distribution of bone tissue mineral are key determinants of bone
      strength. Recent research revealed altered mineral distribution within sheep
      femora following estrogen deficiency. Rapid increases in bone remodeling occur at
      the onset of estrogen deficiency and abate over time. Therefore, altered tissue
      mineralization might be a transient characteristic of osteoporosis.
      Bisphosphonates reduce fracture incidence by 40-60% but increases in bone mineral
      density are insufficient to explain such changes. In this study the hypotheses
      that bone tissue mineralization is altered over prolonged estrogen depletion and
      bisphosphonate treatment were tested. Quantitative backscattered imaging (qBEI)
      was used to quantify bone mineral density distribution (BMDD) parameters (mean,
      FWHM) in trabeculae from the proximal femora of an ovariectomized sheep model
      that underwent estrogen deficiency for 31 months, an ovariectomized group
      administered with Zoledronic acid and age-matched controls. To assess the effects
      of normal ageing and prolonged estrogen deficiency, data were compared to BMDD
      data from sheep that were estrogen deficient for 12 months and age-matched
      controls. This study reports that normal ageing increases mean mineralization and
      mineral heterogeneity at a trabecular level. In contrast, prolonged estrogen
      deficiency leads to significantly decreased mean mineralization and further
      exacerbates increases in mineral heterogeneity. Interestingly, ZOL treatment of
      OVX sheep significantly reduced tissue mineral variability, both at a trabecular
      level and between femoral regions. Together, these findings indicate that ZOL
      treatment acts to reverse the increased mineral heterogeneity occurring during
      estrogen deficiency, which may contribute to its capacity to reduce osteoporotic
      fractures. 

PMID- 24090876
TI  - Effects of a zirconate coupling agent incorporated into an experimental resin
      composite on its compressive strength and bonding to zirconia.
AB  - AIM: To assess in vitro the compressive strength of an experimental zirconate
      coupling agented resin composite and its bonding to dental zirconia ceramics.
      METHODS: Various ratios (1.5-4.0wt%) of a zirconate coupling agent, NZ-33((r)),
      zirconium(IV)-2,2[(bis-2-propenolatomethyl)butanolato-tris-2-methyl-2-propenoato
      O)] were incorporated in an experimental bis-GMA/MMA-based resin composite
      formulation with silica fillers. Compressive strength of the experimental resin
      composite and shear bond strength (SBS) of the resin composite to zirconia were
      evaluated by using a universal testing machine. Specimens were stored in dry
      condition, in water storage for 7 days and for 14 days, to a total of twenty test
      groups. The data were analyzed by one-way ANOVA and Tukey post hoc test
      (alpha=0.05). RESULTS: SBS of resin-to-zirconia bonding and compressive strength
      both have significant increase at 1.5wt% and 3.0wt% NZ-33((r)) (p<0.05). However,
      water storage for 7 days (p>0.05) and 14 days (p>0.05) significantly decreased
      SBS of the experimental resin-to-zirconia with no significant difference between
      groups (p>0.05). CONCLUSIONS: An addition of a zirconate coupling agent used
      might strengthen the biomechanical properties of the experimental resin
      composite.

PMID- 24090877
TI  - Adult neural stem cells and their niche: a dynamic duo during homeostasis,
      regeneration, and aging.
AB  - Stem cells persist in specialized niches in the adult mammalian brain. Emerging
      findings highlight the complexity and heterogeneity of different compartments in
      the niche, as well as the presence of local signaling microdomains. Stem cell
      quiescence and activation are regulated not only by anchorage to the niche and
      diffusible signals, but also by biophysical properties, including fluid dynamics.
      Importantly, the adult neural stem cell niche integrates both local and systemic
      changes, reflecting the physiological state of the organism. Moreover niche
      signaling is bidirectional, with stem cells and their progeny and niche cells
      dynamically interacting with each other during homeostasis, regeneration and
      aging. 

PMID- 24090878
TI  - Facial motor neuron migration advances.
AB  - During development, the migration of specific neuronal subtypes is required for
      the correct establishment of neural circuits. In mice and zebrafish, facial
      branchiomotor (FBM) neurons undergo a tangential migration from rhombomere 4
      caudally through the hindbrain. Recent advances in the field have capitalized on
      genetic studies in zebrafish and mouse, and high-resolution time-lapse imaging in
      zebrafish. Planar cell polarity signaling has emerged as a critical conserved
      factor in FBM neuron migration, functioning both within the neurons and their
      environment. In zebrafish, migration depends on specialized 'pioneer' neurons to
      lead follower FBM neurons through the hindbrain, and on interactions with
      structural components including pre-laid axon tracts and the basement membrane.
      Despite fundamental conservation, species-specific differences in migration
      mechanisms are being uncovered. 

PMID- 24090880
TI  - Simulation-based particle swarm optimization and mechanical validation of screw
      position and number for the fixation stability of a femoral locking compression
      plate.
AB  - Locking compression plates (LCPs) have been used to fix femoral shaft fractures.
      Previous studies have attempted to identify the best LCP screw positions and
      numbers to achieve the fixation stability. However, the determined screw
      positions and numbers were mainly based on the surgeons' experiences. The aim of
      this study was to discover the best number and positions of LCP screws to achieve
      acceptable fixation stability. Three-dimensional numerical models of a fractured
      femur with the LCP were first developed. Then, the best screw position and number
      of LCPs were determined by using a simulation-based particle swarm optimization
      algorithm. Finally, the results of the numerical study were validated by
      conducting biomechanical tests. The results showed that the LCP with six locking
      screws resulted in the necessary fixation stability, and the best combination of
      positions of locking screws inserted into the LCP was 1-5-6-7-8-12 (three locking
      screws on either side of the bone fragment with two locking screws as close as
      practicable to the fracture site). In addition, the numerical models and
      algorithms developed in this study were validated by the biomechanical tests.
      Both the numerical and experimental results can provide clinical suggestions to
      surgeons and help them to understand the biomechanics of LCP systems. 

PMID- 24090879
TI  - Creating a neural specific chromatin landscape by npBAF and nBAF complexes.
AB  - Several features make the chromatin environment of neurons likely to be different
      than any other cell type. These include the fact that several hundred types of
      neurons exist, each requiring specialized patterns of gene expression and in turn
      specialized chromatin landscapes. In addition, neurons have the most stable
      morphology of any cell type, a unique feature essential for memory. Yet these
      stable morphologies must allow the emergence of new stable morphologies in
      response to environmental influences permitting learning to occur by altered
      morphology and new synapse formation. Several years ago we found that neurons
      have specific chromatin remodeling mechanisms not present in any other cell type
      that are produced by combinatorial assembly of ATP-dependent chromatin remodeling
      complexes. The neural specific subunits are essential for normal neural
      development, learning and memory. Remarkably, recreating these neural specific
      complexes in fibroblasts leads to their conversion to neurons. Recently, the
      subunits of these complexes have been found to have genetically dominant roles in
      several human neurologic diseases. The genetic dominance of these mutations
      suggests that less severe mutations will contribute to phenotypic variation in
      human neuronally derived traits. 

PMID- 24090881
TI  - Coastal urbanization leads to remarkable seaweed species loss and community
      shifts along the SW Atlantic.
AB  - Coastal urbanization is rapidly expanding worldwide while its impacts on seaweed
      communities remain poorly understood. We assessed the impact of urbanization
      along an extensive latitudinal gradient encompassing three phycogeographical
      regions in the SW Atlantic. Human population density, number of dwellings, and
      terrestrial vegetation cover were determined for each survey area and correlated
      with diversity indices calculated from seaweed percent cover data. Urban areas
      had significantly lower calcareous algal cover (-38%), and there was
      significantly less carbonate in the sediment off urban areas than off reference
      areas. Seaweed richness averaged 26% less in urban areas than in areas with
      higher vegetation cover. We observed a remarkable decline in Phaeophyceae and a
      substantial increase of Chlorophyta in urban areas across a wide latitudinal
      gradient. Our data show that coastal urbanization is causing substantial loss of
      seaweed biodiversity in the SW Atlantic, and is considerably changing seaweed
      assemblages. 

PMID- 24090882
TI  - Marine water quality monitoring: a review.
AB  - Marine water quality monitoring is performed for compliance with regulatory
      issues, trend detection, model validation and assessment of the effectiveness of
      adopted policies. As the end users are managers and policy makers, the objectives
      should be of practical interest and the answers should reduce the uncertainty
      concerning environmental impact, supporting planning and decision making. Simple
      and clearcut answers on environmental issues require synthesis of the field
      information using statistics, simulation models and multiple criteria analysis
      (MCA). Statistics is easy to apply whereas simulation models enable researchers
      to forecast future trends as well as test different scenarios. MCA allows the co
      estimation of socio-economic variables providing a compromise between scientists'
      and policy makers' priorities. In addition, stakeholders and the public have the
      right to know and participate. This article reviews marine water quality
      monitoring principles, design and data analysis procedures. A brief review of
      international conventions of regional seas is also included. 

PMID- 24090883
TI  - Single amino acid substitutions in recombinant plant-derived human alpha1
      proteinase inhibitor confer enhanced stability and functional efficacy.
AB  - BACKGROUND: Human alpha1-proteinase inhibitor (alpha1-PI) is the most abundant
      serine protease inhibitor in the blood and the heterologous expression of
      recombinant alpha1-PI has great potential for possible therapeutic applications.
      However, stability and functional efficacy of the recombinant protein expressed
      in alternate hosts are of major concern. METHODS: Five variants of plant
      expressed recombinant alpha1-PI protein were developed by incorporating single
      amino acid substitutions at specific sites, namely F51C, F51L, A70G, M358V and
      M374I. Purified recombinant alpha1-PI variants were analyzed for their
      expression, biological activity, oxidation-resistance, conformational and thermal
      stability by DAC-ELISA, porcine pancreatic elastase (PPE) inhibition assays,
      transverse urea gradient (TUG) gel electrophoresis, fluorescence spectroscopy and
      far-UV CD spectroscopy. RESULTS: Urea-induced unfolding of recombinant alpha1-PI
      variants revealed that the F51C mutation shifted the mid-point of transition from
      1.4M to 4.3M, thus increasing the conformational stability close to the human
      plasma form, followed by F51L, A70G and M374I variants. The variants also
      exhibited enhanced stability for heat denaturation, and the size-reducing
      substitution at Phe51 slowed down the deactivation rate ~5-fold at 54 degrees C.
      The M358V mutation at the active site of the protein did not significantly affect
      the conformational or thermal stability of the recombinant alpha1-PI but provided
      enhanced resistance to oxidative inactivation. CONCLUSIONS: Our results suggest
      that single amino acid substitutions resulted in improved stability and oxidation
      resistance of the plant-derived recombinant alpha1-PI protein, without inflicting
      the inhibitory activity of the protein. GENERAL SIGNIFICANCE: Our results
      demonstrate the significance of engineered modifications in plant-derived
      recombinant alpha1-PI protein molecule for further therapeutic development.

PMID- 24090884
TI  - Human aquaporins: regulators of transcellular water flow.
AB  - BACKGROUND: Emerging evidence supports the view that (AQP) aquaporin water
      channels are regulators of transcellular water flow. Consistent with their
      expression in most tissues, AQPs are associated with diverse physiological and
      pathophysiological processes. SCOPE OF REVIEW: AQP knockout studies suggest that
      the regulatory role of AQPs, rather than their action as passive channels, is
      their critical function. Transport through all AQPs occurs by a common passive
      mechanism, but their regulation and cellular distribution varies significantly
      depending on cell and tissue type; the role of AQPs in cell volume regulation
      (CVR) is particularly notable. This review examines the regulatory role of AQPs
      in transcellular water flow, especially in CVR. We focus on key systems of the
      human body, encompassing processes as diverse as urine concentration in the
      kidney to clearance of brain oedema. MAJOR CONCLUSIONS: AQPs are crucial for the
      regulation of water homeostasis, providing selective pores for the rapid movement
      of water across diverse cell membranes and playing regulatory roles in CVR.
      Gating mechanisms have been proposed for human AQPs, but have only been reported
      for plant and microbial AQPs. Consequently, it is likely that the distribution
      and abundance of AQPs in a particular membrane is the determinant of membrane
      water permeability and a regulator of transcellular water flow. GENERAL
      SIGNIFICANCE: Elucidating the mechanisms that regulate transcellular water flow
      will improve our understanding of the human body in health and disease. The
      central role of specific AQPs in regulating water homeostasis will provide routes
      to a range of novel therapies. This article is part of a Special Issue entitled
      Aquaporins.

PMID- 24090885
TI  - [Aesthetic aspects of eyelid reconstruction].
AB  - In eyelid reconstruction, filling the defect is not sufficient. In young
      patients, the aim is to obtain a reconstructed eyelid, as normal as possible. In
      elderly patients, the large amount of available skin and the good quality of
      scars seem to be favorable. But weakening and stretching of the connective tissue
      and eyelid structures and deficient production of tears may compromise the
      functional result. In every case, restoring aspect and function are going
      together. The purpose of this chapter is to show how different techniques may be
      used in eyelid reconstruction with good cosmetic result. Different cases are
      carefully described and illustrated. 

PMID- 24090887
TI  - ["Caucasian" you say?].

PMID- 24090886
TI  - The effects of an obesogenic diet during pregnancy on fetal growth and placental
      gene expression are gestation dependent.
AB  - Exposure to overnutrition in utero may increase offspring cardiometabolic disease
      risk. A mouse model of maternal exposure to an obesogenic diet (DIO) was used to
      determine effects on fetal and placental weight and gene expression in mid- and
      late gestation. DIO altered placental gene expression in mid-gestation without
      differences in fetal or placental weights. Weight gain was attenuated in DIO dams
      in late gestation and male pup weight was reduced, however there were no
      persistent changes in placental gene expression. Differences in maternal weight
      gain and/or specific dietary components may impact on fetal and placental growth
      and later disease risk. 

PMID- 24090888
TI  - [Sclerodermatous changes in porphyria cutanea tarda: six cases].
AB  - BACKGROUND: The clinical features of porphyria cutanea tarda (PCT) are usually
      distinctive and include blistering on sun-exposed areas, fragile skin,
      hypertrichosis and hyperpigmentation. Sclerodermatous changes are much less
      common, and may either reveal PCT or else appear later. We carried out a
      retrospective study of the files of six female patients presenting such lesions.
      PATIENTS AND METHODS: Six women (age: 45 to 72 years) were referred for
      sclerodermatous lesions on sun-exposed areas of the upper body. In four patients,
      these lesions revealed PCT and in the remaining two patients they were indicative
      of previously treated but relapsing PCT. Four had sclerodermatous skin changes
      mimicking morphea of the neck and neckline, the top of the back and the face,
      while one presented more diffuse facial and cervical sclerosis. Associated
      alopecia was seen in three patients. The last patient presented isolated
      sclerodermiform alopecia. Associated malar hypertrichosis was seen in five cases
      and facial hyperpigmentation was noted in three cases. Four exhibited no
      blisters, cutaneous fragility, milia or photosensitivity. Histological findings
      were consistent with morphea or scleroderma in all cases. All patients presented
      abnormal liver tests: cirrhosis was present in four cases (primitive biliary
      cirrhosis, alcoholic cirrhosis and hepatitis C) and fatty liver in two cases. In
      four cases, there was excessive alcohol intake. Uroporphyrin levels were above
      the normal range in all cases. Local corticosteroid therapy associated with
      phlebotomy and/or low-dose hydroxychloroquine resulted in complete normalisation
      of porphyrin levels in four patients, with complete resolution of the cutaneous
      lesions in two patients and partial improvement in the other two. DISCUSSION:
      Sclerodermatous changes are uncommon in PCT. They are not always late and
      secondary to the process of healing of blisters but can in fact constitute the
      first cutaneous symptom of the disease while revealing the underlying liver
      disease. Even in the absence of blisters, photosensitivity or cutaneous
      fragility, a diagnosis of PCT must be suspected in a setting of sclerodermatous
      changes distributed on the neck and face, or the neckline, or scarring alopecia,
      if associated with abnormal liver tests. Skin biopsy to confirm the diagnosis of
      scleroderma may delay the diagnosis, which is in fact based on porphyrin level.
      Normalization of the latter parameter under treatment allows regression of
      lesions.

PMID- 24090889
TI  - [Update on SENLAT syndrome: scalp eschar and neck lymph adenopathy after a tick
      bite].
AB  - SENLAT syndrome, also known as TIBOLA/DEBONEL, is an emerging disease in France.
      The major symptoms are necrotic eschar on the scalp associated with painful
      cervical lymphadenopathy. It occurs mainly in women and children during the cold
      seasons after a bite by a Dermacentor tick, responsible for transmitting
      Rickettsia slovaca or Rickettsia raoultii. Cutaneous swabs are safe, easy and
      reliable tools that should be used routinely by physicians to confirm diagnosis.
      In this particular disease, they should be preferred to serology, which is less
      sensitive. Doxycycline is the antibiotic of choice for this syndrome. 

PMID- 24090890
TI  - [Finger onychomycosis due to Candida tropicalis: short-pulsed Nd:YAG laser
      therapy].
AB  - BACKGROUND: Treatment options for onychomycosis are numerous but of limited
      efficacy, potentially dangerous and/or relatively restrictive. PATIENTS AND
      METHODS: We describe the first case of Candida tropicalis onychomycosis resistant
      to standard topical treatments successfully treated with four sessions of Nd:YAG
      laser in Short Pulse mode. The efficacy of treatment was verified at 3 months via
      a negative control sample and was maintained for at least 6 months. DISCUSSION:
      Nd:YAG laser is a versatile type of laser widely used in dermatology. Its mode of
      action in the treatment of onychomycosis may consist of a thermal effect that is
      non-specific but differentiates between healthy nail and diseased nail, which
      respond differently to impact. The main interest of this case is in helping to
      pave the way for a new type of treatment for onychomycosis.

PMID- 24090891
TI  - [An uncommon cutaneous presentation of cat scratch disease].
AB  - BACKGROUND: Herein we report a case of cat scratch disease on account of its
      atypical presentation. PATIENTS AND METHODS: A 21-year-old woman presented
      erythema nodosum associated with painful bilateral inguinal adenopathy,
      odynophagia, joint pain and evening urticaria in a setting of impaired general
      condition. Initial serological testing for Bartonella henselae was negative. PCR
      for Bartonella henselae performed on an adenectomy fragment was positive. A
      favourable outcome was achieved with azithromycin. COMMENTS: This case shows an
      atypical and severe presentation of cat scratch disease and raises the problem of
      sensitivity of serotyping.

PMID- 24090892
TI  - [A case of neurological syphilis mimicking Horton's disease and polymyalgia
      rheumatica].
AB  - BACKGROUND: Syphilis has been making a comeback over the last 10 years.
      Neurosyphilis can occur at any stage of the infection but is difficult to
      diagnose because of the existence of misleading forms, of which we describe an
      example below. PATIENTS AND METHODS: A 56-year-old woman presented symptoms
      evoking polymyalgia rheumatica and giant-cell arteritis in a context of ibuprofen
      treatment for a few weeks. She also had myodesospsia, syphilids and syphilitic
      roseola, together with laboratory indicators of inflammation. A lumbar puncture
      revealed lymphocytic meningitis and a positive Treponema Pallidum
      Haemagglutination Assay (TPHA) for cerebrospinal fluid, thus confirming the
      diagnosis of neurosyphilis. Moreover, the ophthalmologic examination showed optic
      neuritis with papilla lesions of syphilitic origin. This was successfully treated
      with a 3-week course of penicillin G infusions. CONCLUSION: Symptoms evocative of
      Horton's disease and polymyalgia rheumatica can reveal syphilis, a disease dubbed
      "the great simulator" on account of the variety of clinical forms it can take.

PMID- 24090893
TI  - [Buccal infection with Gongylonema pulchrum: an indigenous case in France].
AB  - BACKGROUND: Although long known, infestations of the buccal mucosa by nematodes
      of the Gongylonema genus are rare, particularly in France. Herein we report a new
      case. PATIENTS AND METHODS: A 48-year old man consulted for itching in various
      parts of the buccal mucosa over the preceding weeks. The patient lived in a rural
      region in southern Alsace and had never visited Africa. His work comprised
      overseeing the unloading of flour at the port of Basel. The initial clinical
      examination was negative. However, the patient managed to photograph a filament
      previously present in his buccal mucosa, and to ultimately extract a worm. The
      latter was identified at the Strasbourg Institute of Parasitology by Pr Pesson as
      a nematode of the genus Gongylonema sp. pulchrum. No other treatment was
      considered necessary. DISCUSSION: It is important for dermatologists to be aware
      of this type of parasitosis. Its stereotyped clinical presentation allows ready
      diagnosis, but the possible absence of the parasite at the time of the visit may
      lead to a misdiagnosis of Ekbom syndrome (delusional parasitic infestation).

PMID- 24090894
TI  - [Dermatomyositis and acute interstitial lung disease associated with MDA-5
      antibodies: an atypical case].
AB  - BACKGROUND: A new antibody known as anti-MDA-5 has recently been identified in
      association with a specific phenotype of dermatomyositis (DM), in which muscular
      involvement is minimal or absent, but where there is a particularly high risk of
      onset of aggressive interstitial lung disease. Below, we report a case associated
      with the presence of anti-MDA-5 antibodies complicated by aggressive interstitial
      lung disease ; the cutaneous phenotype of this patient is novel due to the
      constitution of diffuse ichthyosis and of profuse subcutaneous calcinosis.
      PATIENTS AND METHODS: A 35-year-old man was hospitalised for a skin rash
      associated with arthralgia, dry cough, asthenia and weight-loss of 8 kg in 5
      months. The dermatological examination revealed purple erythema of the upper
      eyelids and cheeks, diffuse acquired ichthyosis of the trunk and limbs, and
      striated erythema on the proximal and distal metacarpal and interphalangeal
      joints of the fingers. A diagnosis of DM was suspected in patients treated with
      prednisolone, 1.5 mg/kg/d. Immunological tests identified the presence of anti
      MDA-5 antibodies. One month later, the cutaneous signs continued to progress and
      were marked by the development of painful ulcers on the back of the fingers, as
      well as dyspnoea accompanying the slightest effort. Chest images showed
      constituted pulmonary fibrosis lesions. At the same time, within several months,
      diffuse, pseudo-tumoural calcifications developed in the subcutaneous tissue of
      the trunk and limbs. The patient was treated successively with intravenous
      gammaglobulins, cyclophosphamide, mycophenolate mofetil, azathioprine and
      rituximab in combination with oral corticosteroids, but with no improvement in
      respiratory function or in the skin lesions. Because of the decline in the
      patient's respiratory status, a lung graft was envisaged but subsequently
      abandoned because of the patient's excessively precarious state of health.
      DISCUSSION: Anti-MDA-5 antibody appears to constitute a specific immunological
      marker for a special dermatological phenotype of adult DM, significantly
      associated with the presence of: 1) keratotic papules in the skin folds of the
      palms and fingers ; 2) cutaneous ulcers along the periungueal edges, Gottron's
      papules on the back of the hands and on the extensor surface of the elbows and
      knees ; 3) pain and ulceration in the oral mucosa, diffuse alopecia, and
      appearance of "mechanic's hands" and Gottron's sign on the elbows and knees. To
      our knowledge, the presence of extensive ichthyosis and profuse subcutaneous
      calcinosis has not been previously reported in this particular form of DM. The
      risk of aggressive interstitial lung disease is particularly high and worsens the
      prognosis, since 40% of patients with anti-MDA-5 die, usually within the first
      year. CONCLUSION: Herein, we describe a patient presenting amyopathic DM
      complicated by aggressive interstitial lung disease associated with the presence
      of anti-MDA-5 antibodies, but with a hitherto unreported cutaneous phenotype
      combining diffuse ichthyosis and profuse subcutaneous calcinosis.

PMID- 24090895
TI  - [Acute neutrophilic dermatosis (pustular dermatitis) associated with aggressive
      transformed mycosis fungoides].
AB  - BACKGROUND: Large-cell transformation in mycosis fungoides [MF] is associated
      with an aggressive clinical course and poor survival. In addition to tumour
      progression, infectious complications may be the cause of death. We report a case
      of aseptic pustular dermatosis in transformed MF that very quickly became
      aggressive and was followed by rapid death of the patient. PATIENTS AND METHODS:
      A 47-year-old man presented with disseminated CD30+ transformed MF skin tumours
      refractory to chemotherapy for nine consecutive months. Ten days after a first
      course of dexamethasone, cytarabine and carboplatin, he was hospitalized for
      febrile neutropenia. Following this episode of neutropenia, he developed a
      febrile pustular rash disseminated on the tumours and on plaques, associated with
      marked neutrophilic leucocytosis. Bacteriological and mycological skin and blood
      samples were negative. Tumour biopsies showed a dermal infiltrate of CD30+ T
      cells corresponding to the transformed MF, mixed with neutrophils. The pustule
      biopsies revealed intra-epidermal pustules and dermal-epidermal infiltration of
      neutrophils. The pustular eruption regressed with corticosteroids. Despite a last
      line of treatment with romidepsin, the patient died 6 weeks after the
      "neutrophilic" event. DISCUSSION: Episodes of neutrophilic dermatosis [ND] are
      frequently seen in haematological disease and some substances can induce a
      variant form of eccrine hidradenitis. However, our patient's presentation was
      different, without the appearance of "classic" ND but rather diffuse pustular
      lesions carrying a poor prognosis, which was followed by rapid death. Once the
      hypothesis of infectious complications has been ruled out, treatment is based on
      systemic corticosteroids associated with specific treatment of the lymphoma.

PMID- 24090897
TI  - [Home ultraviolet phototherapy].

PMID- 24090896
TI  - [IgE mediated anaphylaxis in a patient with systemic mastocytosis].
AB  - BACKGROUND: Anaphylaxis is a severe, generalized, life-threatening reaction of
      rapid onset. We report the case of a patient presenting several systemic
      anaphylactic reactions over many years, initially ascribed to a cereals allergy
      but which finally proved to be due to systemic mastocytosis hidden for a long
      time. PATIENTS AND METHODS: A 53-year-old man consulted for an eruption
      consisting of monomorphic pigmented maculopapular lesions on the trunk associated
      with itching and urticaria. He was a farmer and presented severe sensitivity to
      cereals, with anaphylaxis, which continued despite withdrawal of these allergens.
      Skin and bone marrow infiltration, abnormal mast cells, positivity for c-kit 816
      mutation and the persistent elevation of serum tryptase enabled a diagnosis of
      indolent systemic mastocytosis to be made. DISCUSSION: In systemic mastocytosis
      anaphylaxis is an expected complication relating to the proliferation of mast
      cells and a massive increase in mediator release (non-immunological mechanism).
      All patients with severe and recurrent anaphylaxis should be analyzed for
      underlying mastocytosis by careful physical examination and assay of baseline
      tryptase.

PMID- 24090898
TI  - [Micrographic surgery: indications and practical applications in the
      dermatologist's office].

PMID- 24090899
TI  - [Histopathology of scabies].

PMID- 24090900
TI  - [Sturge-Weber syndrome and port-wine stains: causative role of postzygotic
      somatic mutations in GNAQ].

PMID- 24090901
TI  - [Kaposi sarcoma mimicking pyogenic granuloma].

PMID- 24090903
TI  - [Primary penile tuberculosis].

PMID- 24090902
TI  - [Lymphoedema distichiasis].

PMID- 24090904
TI  - [Exacerbation of psoriasiform lesions by a gamma-secretase inhibitor].

PMID- 24090905
TI  - Infliximab concentrations in the milk of nursing mothers with inflammatory bowel
      disease.

PMID- 24090906
TI  - Reply to Dr. Selinger et al.'s letter.

PMID- 24090907
TI  - Dietary calcium intake in patients with inflammatory bowel disease.
AB  - BACKGROUND & AIMS: Osteopenia and increased risk for fractures in IBD result from
      several factors. AIM OF THE STUDY: To investigate the dietary intake of calcium
      in IBD patients. METHODS: A 22-item quantitative validated frequency food
      questionnaire was used for quantifying dietary calcium in relation to gender and
      age, in 187 IBD patients, 420 normal- and 276 diseased controls. STATISTICAL
      ANALYSIS: Mann-Whitney, chi-square- and T-tests. RESULTS: The mean calcium intake
      was 991.0 +/- 536.0 (105.8% Recommended Daily Allowances) and 867.6 +/- 562.7 SD
      mg/day (93.8% RDA) in healthy and diseased controls, and 837.8 +/- 482.0 SD
      mg/day (92.7% RDA) in IBD, P<0.001. Calcium intake was high in celiac disease
      (1165.7 +/- 798.8 SD mg/day, 120% RDA), and non-significantly lower in ulcerative
      colitis than in Crohn's disease (798.7 +/- 544.1 SD mg/day vs 881.9 +/- 433.0).
      CD and UC females, but not males, had a mean calcium intake well under RDA. In
      all study groups the intake was lower in patients believing that consumption of
      lactose-containing food induced symptoms, versus those who did not (105.8% vs
      114.3% RDA in normal controls; 100.4% vs 87.6% RDA in IBD). CONCLUSIONS: Diet in
      IBD patients contained significantly less calcium than in healthy controls.
      Gender and age, more than diagnosis, are central in determining inadequate
      calcium intake, more so in IBD. Self-reported lactose intolerance, leading to
      dietary restrictions, is the single major determinant of low calcium intake.
      Inadequate calcium intake is present in one third of IBD patients and represents
      a reversible risk factor for osteoporosis, suggesting the need for tailored
      nutritional advice in IBD.

PMID- 24090908
TI  - Cryptogenic organizing pneumonia: a rare extra-intestinal manifestation of
      Crohn's disease.

PMID- 24090909
TI  - Effective removal of colistin methanesulphonate and formed colistin during
      intermittent haemodialysis in a patient infected by polymyxin-only-susceptible
      Pseudomonas aeruginosa.
AB  - Colistin use has reemerged for the treatment of infections caused by multidrug
      resistant Gram-negative bacteria. However, the information on its
      pharmacokinetics is limited, especially in patients with end-stage renal disease,
      in which dosage adjustments are contradictory, and evidences the need to
      investigate the removal of colistin through renal replacement therapies like
      haemodialysis. This case study showed efficient removal of colistin
      methanesulphonate and formed colistin during intermittent haemodialysis in a
      patient infected by polymyxin-only-susceptible Pseudomonas aeruginosa. These
      results suggest the importance to monitor colistin plasma concentrations in these
      patients to minimize treatment failure due to suboptimal exposure to
      antibacterial colistin. 

PMID- 24090910
TI  - Squamous cell carcinoma originating in the parotid gland: MRI features with
      histopathological correlation.
AB  - AIM: To report the magnetic resonance imaging (MRI) and corresponding
      histopathological features of squamous cell carcinoma (SCC) originating in the
      parotid gland. MATERIALS AND METHODS: The MRI images of seven patients with
      histopathologically proven SCC originating in the parotid gland were reviewed
      retrospectively, with an emphasis on tumour size, shape, contour definition,
      extraparotid infiltration, signal characteristics, and the presence of central
      necrosis. These were correlated with the microscopic findings of the surgical
      specimens. RESULTS: The tumours ranged in size from 3.9-7 cm (mean 4.7 cm). All
      tumours had an ill-defined margin with extraparotid infiltration, which seemed to
      reflect the invasive growth of the tumour cells on histopathological examination.
      The solid portions of the tumours showed predominantly low to intermediate signal
      intensities on T2-weighted images, which seemed to reflect the high cellularity,
      intercellular bridges, and/or keratin pearl formation observed at
      histopathological examination. Five of the seven tumours had central necrosis.
      CONCLUSION: A relatively large tumour with central necrosis is a useful imaging
      feature of SCCs originating in the parotid gland, in addition to the well
      recognized indicators of parotid malignancy, such as an ill-defined margin,
      extraparotid infiltration, and low to intermediate signal intensity on T2
      weighted images.

PMID- 24090911
TI  - Multiple injuries in a 3-year-old Nigerian girl: an extreme form of physical
      abuse.
AB  - Physical abuse and other forms of child maltreatment occur worldwide. However, in
      developing countries such as Nigeria they are not often considered in the
      differential diagnosis. A 3-year-old girl is presented who sustained injuries
      including traumatic teeth extraction, multiple bruises, femoral shaft fracture
      and haemorrhage resulting in severe anaemia as a result of physical assault by
      her father. This case underscores the need for the implementation of appropriate
      legislation to combat child maltreatment in Nigeria. 

PMID- 24090912
TI  - Design, synthesis, and biological evaluation of novel 2-ethyl-5-phenylthiazole-4
      carboxamide derivatives as protein tyrosine phosphatase 1B inhibitors with
      improved cellular efficacy.
AB  - Protein tyrosine phosphatase 1B (PTP1B) is implicated as a key negative regulator
      of the insulin and leptin signal-transduction pathways. PTP1B inhibitors have
      emerged as attractive and potent pharmaceutical agents for the treatment of type
      2 diabetes and obesity. We identified a series of 2-ethyl-5-phenylthiazole-4
      carboxamide (PTA) derivatives, inspired from the ACT scaffold of Scleritodermin
      A, as a novel class of PTP1B inhibitors. Structure-activity relationship (SAR)
      analysis and docking studies revealed the molecular basis of PTP1B inhibition by
      these compounds. PTA derivative 18g was capable of inhibiting intracellular PTP1B
      and subsequently activating the insulin signaling pathway. Treatment of cells
      with 18g markedly increased the phosphorylation levels of IRbeta and Akt as well
      as the rate of glucose uptake. 

PMID- 24090913
TI  - Synthesis and biological evaluation of novel delta (delta) opioid receptor
      ligands with diazatricyclodecane skeletons.
AB  - Considering the interesting pharmacological profile of the delta (delta)
      selective opioid agonist compound SNC-80, conformationally constrained analogs
      containing two diazatricyclodecane ring systems in place of dimethylpiperazine
      core motif were synthesized. The compounds showed subnanomolar or low nanomolar
      delta opioid receptor binding affinity. Depending upon the substituents on the
      diazatricyclodecane ring, these compounds displayed varying selectivity for delta
      opioid receptor over MU and kappa receptors. Amongst the novel compounds, 1Aa
      showed the more interesting biological profile, with higher delta affinity and
      selectivity compared to SNC-80. The delta receptor agonist profile and
      antinociceptive activity of 1Aa were confirmed using ex-vivo (isolated mouse vas
      deferens) and in vivo (tail flick) assays.

PMID- 24090914
TI  - Novel N-4-piperazinyl-ciprofloxacin-chalcone hybrids: synthesis, physicochemical
      properties, anticancer and topoisomerase I and II inhibitory activity.
AB  - A group of novel N-4-piperazinyl-ciprofloxacin-chalcone hybrids was prepared. One
      dose anticancer test results indicated that compounds 3a and 3g exhibited the
      highest ability to inhibit the proliferation of different cancer cell lines.
      Compound 3a exhibited a broad-spectrum of anti-tumor activity without pronounced
      selectivity while compound 3g revealed high selectivity toward the leukemia
      subpanel with selectivity ratio of 6.71 at GI50 level. Moreover, compounds 3e and
      3j have shown remarkable topo II inhibitory activity compared to etoposide at 100
      MUM and 20 MUM concentrations. Compounds 3e and 3j exhibited comparably potent
      topo I inhibitory activity at 20 MUM concentration compared to camptothecin.
      Compounds 3e and 3j exhibited strong topo II inhibitory activities compared to
      topo I at 20 MUM concentration. Studying of the solubility and partition
      coefficient revealed higher lipophilicity of the hybrids 3a-j compared to the
      parent ciprofloxacin.

PMID- 24090915
TI  - Synthesis of new andrographolide derivatives and evaluation of their
      antidyslipidemic, LDL-oxidation and antioxidant activity.
AB  - Andrographis paniculata, native to Taiwan, Mainland China and India, is a
      medicinal herb, which possesses various biological activities including anti
      atherosclerosis. Andrographolide (1) has been identified as one of the active
      constituents against atherosclerosis. In continuation of our drug discovery
      program we synthesized few novel derivatives of 1 to improve their
      antidyslipidemic, LDL-oxidation and antioxidant activity. The tosylated
      derivative 7 has been turned out to be more potent than the parent compound and
      comparable activity with marketed antidyslipidemic drugs. 

PMID- 24090916
TI  - Synthesis of lipoic acid-peptide conjugates and their effect on collagen and
      melanogenesis.
AB  - We report new examples of lipoic acid (LA)-peptide conjugates, their potential as
      codrugs having anti-melanogenic and anti-aging properties was evaluated. These
      multifunctional molecules were prepared by linking lipophilic moiety (LA) to the
      pentapeptide KTTKS. The inhibitory effect of LA-peptide conjugates on melanin
      synthesis and tyrosinase activity is stronger than that of LA or the pentapeptide
      alone. Importantly, the conjugates display no cytotoxicity at a high
      concentration. LA-KTTKS and LA-PEG-KTTKS also inhibit UV-induced matrix
      metalloproteinase-1 expression up to 49.5% and 69.5% at 0.5 mM, respectively. LA
      peptide conjugates stimulate collagen biosynthesis in fibroblasts more
      efficiently than their parent molecules do. These data suggest that LA-peptide
      conjugates may have cosmeceutical application as anti-melanogenic and anti-aging
      agents.

PMID- 24090917
TI  - Synthesis, physicochemical properties of allopurinol derivatives and their
      biological activity against Trypanosoma cruzi.
AB  - Chagas disease is caused by Trypanosoma cruzi (T. cruzi) leading to a huge number
      of infections and deaths per year, because in addition to many sufferers only
      having limited access to health services only an inefficient chemotherapy is
      available using drugs such as benznidazole and nifurtimox. Here, C6-alkyl (2a-c)
      and N1-acyl (3a-c) derivatives of Allopurinol (Allop, compound with activity
      against T. cruzi) were synthesized in good yields and their structures were
      unambiguously characterized. Only 2a, 2b and 3c showed inhibitory activity
      against the proliferative stages of the parasite when tested at 1 MUg mL(-1) with
      the 3c derivative exhibiting an IC50 value similar to that of Allop and not being
      toxic for mammalian cells. Relevant pharmaceutical physicochemical properties
      (pKa, stability, solubility, lipophilicity) were also determined as well by using
      Lipinski's rule, polar surface area and molecular rigidity. Taken together, the
      results demonstrated that the studied derivatives had optimal properties for
      bioavailability and oral absorption. For the stability studies, Micellar Liquid
      Chromatography was used as the analytical method which was fully validated
      according to the FDA guidelines and shown to be a suitable, sensitive and simple
      method for routine analysis of these Allop derivatives.

PMID- 24090918
TI  - Indenoindoles and cyclopentacarbazoles as bioactive compounds: synthesis and
      biological applications.
AB  - Indenoindoles and their isomers cyclopentacarbazoles represent a wide class of
      synthetic and natural compounds. The great interest of these structures in
      (bio)organic chemistry is due to the use of various building blocks to get the
      elemental four ring structure. Depending on the synthetic route chosen, the
      chemists can achieve a large number of regioisomers. Each regioisomer can be
      considered as a template for specific functionalizations. Therefore, this mini
      review aims (i) to present an overview on how to access this large family of
      heterocyclic compounds and (ii) to discuss their various biological applications
      and drug development in oncology (e.g. kinases), in CNS disorders (e.g.
      Alzheimer's disease), in endocrinology (e.g. hormone replacement therapy) and
      oxidative stress (e.g. organ preservation). Past and present works will be
      presented through the systems 6-5-5-6 and 6-5-6-5 (combination of 6-membered and
      5-membered rings). 

PMID- 24090920
TI  - Novel heterocyclic-fused pyrimidine derivatives: synthesis, molecular modeling
      and pharmacological screening.
AB  - Novel heterocyclic-fused pyrimidines viz pyrrolo[1,2-c]pyrimidines 4-8,
      pyrimido[5,4-e]pyrrolo[1,2-c]pyrimidines 9-14, pyrimido[4',5':4,5]pyrimido[1,6
      a]azepines 16-18, pyrrolo[1',2':1,6]pyrimido[4,5-d][1,3]thiazines 19a,b and 1,3
      thiazino[4',5':4,5]pyrimido[1,6-a]-azepine 19c were designed and synthesized as
      potential anticancer agents. In this investigation all the newly synthesized
      compounds were subjected to cytotoxic screening against MCF-7 breast cancer cell
      line. Moreover, kinase inhibitory assay was done for compounds 5, 7, 9 and 18
      against the non-receptor and receptor tyrosine kinases c-Src and VEGFR,
      respectively. The tested compounds were more potent against c-Src than VEGFR, and
      the highest activity was observed for 18 showing 81% c-Src activity inhibition.
      Finally, molecular docking was performed with c-Src and VEGFR in an attempt to
      simulate and understand the possible binding interactions underlying the
      association between these small molecules and the kinase enzyme ATP binding
      pocket essential amino acids. 

PMID- 24090919
TI  - Design, synthesis and biological evaluation of WC-9 analogs as antiparasitic
      agents.
AB  - As a part of our project pointed at the search of new safe chemotherapeutic and
      chemoprophylactic agents against parasitic diseases, several compounds
      structurally related to 4-phenoxyphenoxyethyl thiocyanate (WC-9), which were
      modified at the terminal aromatic ring, were designed, synthesized and evaluated
      as antiproliferative agents against Trypanosoma cruzi, the parasite responsible
      of American trypanosomiasis (Chagas disease) and Toxoplasma gondii, the
      etiological agent of toxoplasmosis. Most of the synthetic analogs exhibited
      similar antiparasitic activity being slightly more potent than the reference
      compound WC-9. For example, the nitro derivative 13 showed an ED50 value of 5.2
      MUM. Interestingly, the regioisomer of WC-9, compound 36 showed similar
      inhibitory action than WC-9 indicating that para-phenyl substitution pattern is
      not necessarily required for biological activity. The biological evaluation
      against T. gondii was also very promising. The ED50 values corresponding for 13,
      36 and 37 were at the very low micromolar level against tachyzoites of T. gondii.

PMID- 24090921
TI  - Enhanced oral bioavailability of paclitaxel by concomitant use of absorption
      enhancers and P-glycoprotein inhibitors in rats.
AB  - Paclitaxel (PCT) is a cytotoxic agent with a broad antineoplastic activity. IV
      formulation of PCT causes hypersensitivity reactions in some patients and oral
      administration is an alternative to decrease the side effects. PCT is not orally
      available because of low solubility, lack of intestinal permeability, and efflux
      by pumps in intestinal wall. PCT solution in cremophor EL: ethanol (100 mg/kg)
      was administered orally to rats after pre-treatment by mefenamic acid, ibuprofen,
      verapamil, cyclosporine, and verapamil+ibuprofen in individual groups. Ibuprofen
      presented positive effect on intestinal permeation of PCT. C(max) and area under
      the serum concentration versus time curve (AUC) after pre-treatment by ibuprofen
      was decreased when the oral dose of PCT was decreased to 50 and 25 mg/kg, while
      dose-blood concentration relationship was nonlinear. Rise in oral bioavailability
      of PCT after pre-treatment by cyclosporine was lower than ibuprofen. It seems
      that by using ibuprofen in concomitant with potent P-gp inhibitors before PCT
      solution, oral delivery of PCT could be promising.

PMID- 24090923
TI  - Congenital tuberculosis: a rare manifestation of a common disease.
AB  - Congenital tuberculosis is difficult to diagnose unless there is a high index of
      suspicion. A 2-month-old infant boy presented with a history of fever since birth
      and failure to thrive. Chest radiograph demonstrated right upper lobe
      collapse/consolidation and an ultrasonogram of the abdomen showed multiple hypo
      echoic hepatic and splenic lesions, and multiple retroperitoneal nodes. Fine
      needle aspiration of a cervical lymph node detected acid-fast bacilli (AFB). The
      mother's chest radiograph demonstrated features of pulmonary tuberculosis.
      Placental histology detected AFB. The combined clinical and laboratory features
      in both mother and infant supports the diagnosis of congenital tuberculosis. 

PMID- 24090922
TI  - Omega-3 fatty acid deficiency does not alter the effects of chronic fluoxetine
      treatment on central serotonin turnover or behavior in the forced swim test in
      female rats.
AB  - While translational evidence suggests that long-chain omega-3 fatty acid status
      is positively associated with the efficacy of selective serotonin reuptake
      inhibitor drugs, the neurochemical mechanisms mediating this interaction are not
      known. Here, we investigated the effects of dietary omega-3 (n-3) fatty acid
      insufficiency on the neurochemical and behavioral effects of chronic fluoxetine
      (FLX) treatment. Female rats were fed diets with (CON, n=56) or without (DEF,
      n=40) the n-3 fatty acids during peri-adolescent development (P21-P90), and one
      half of each group was administered FLX (10mg/kg/day) for 30days (P60-P90) prior
      to testing. In adulthood (P90), regional brain serotonin (5-HT) and 5
      hydroxyindoleacetic (5-HIAA) concentrations, presynaptic markers of 5-HT
      neurotransmission, behavioral responses in the forced swim test (FST), and plasma
      FLX and norfluoxetine (NFLX) concentrations were investigated. Peri-adolescent n
      3 insufficiency led to significant reductions in cortical docosahexaenoic acid
      (DHA, 22:6n-3) composition in DEF (-25%, p<=0.0001) and DEF+FLX (-28%, p<=0.0001)
      rats. Untreated DEF rats exhibited significantly lower regional 5-HIAA/5-HT
      ratios compared with untreated CON rats, but exhibited similar behavioral
      responses in the FST. In both CON and DEF rats, chronic FLX treatment similarly
      and significantly decreased 5-HIAA concentrations and the 5-HIAA/5-HT ratio in
      the hypothalamus, hippocampus, and nucleus accumbens, brainstem tryptophan
      hydroxylase-2 mRNA expression, and immobility in the FST. While the FLX-induced
      reduction in 5-HIAA concentrations in the prefrontal cortex was significantly
      blunted in DEF rats, the reduction in the 5-HIAA/5-HT ratio was similar to CON
      rats. Although plasma FLX and NFLX levels were not significantly different in DEF
      and CON rats, the NFLX/FLX ratio was significantly lower in DEF+FLX rats. These
      preclinical data demonstrate that n-3 fatty acid deficiency does not
      significantly reduce the effects of chronic FLX treatment on central 5-HT
      turnover or behavior in the FST in female rats. 

PMID- 24090924
TI  - Photoperiodic induced melatonin regulates immunity and expression pattern of
      melatonin receptor MT1 in spleen and bone marrow mononuclear cells of male golden
      hamster.
AB  - The pineal gland transduces day length information into chemical signal of
      melatonin that ultimately translates photic stimulus into season-specific immune
      responses to promote survival of individual from incidence of opportunistic
      diseases. To date, the immune adjustments being a result of photoperiodic
      exposures for any nocturnal seasonally breeding rodent have not been
      systematically examined. Therefore, we evaluated the humoral and cell mediated
      immune responses of photoperiodically entrained male golden hamsters. Short day
      induced melatonin increased the immune parameters such as spleen mass, total
      leukocyte (TLC) and lymphocyte count (LC), proliferation of splenocytes,
      peripheral blood mononuclear cells (PBMCs) and bone marrow mononuclear cells
      (BMMNCs) along with serum IL-2 and anti-Keyhole Limpet Hemocyanin (KLH) IgG
      production when compared with long day experienced hamsters. Short term melatonin
      treatment (for two weeks) to long day hamsters enhanced to some extent the
      proliferation of splenocytes, PBMC and TLC/LC. We also localized the melatonin
      membrane receptor MT1 in spleen and BMMNCs that strongly supported our western
      blot analysis for the expression of MT1 in spleen suggesting that different
      photoperiodically induced circulatory melatonin is responsible for the
      immunomodulation. Therefore, photoperiod can influence the peripheral melatonin
      level to improve immune responses of hamsters according to season for better
      survival. 

PMID- 24090925
TI  - Panoramic radiomorphometry and vertebral fractures in Spanish postmenopausal
      women.
AB  - OBJECTIVE: To evaluate the relationship between panoramic radiomorphometric
      indexes, and the presence of osteoporotic fractures in a Spanish postmenopausal
      women. METHODS: A sample of 120 women (60 with fragility spine fractures and 60
      healthy), aged 55-70 years, with fragility spine fractures, were included in this
      cross-sectional study that was conducted from 2008 to 2011. All the women were
      referred to undergo a radiological spine examination, spinal densitometry and a
      panoramic radiograph for assessing osteoporosis using 3 radiomorphometric
      indexes: Panoramic Mandibular Index (PMI), Mental Index (MI) and Mandibular
      Cortical Index (MCI). According to mandibular cortical shape, in MCI, three
      groups were defined: C3 (osteoporosis), C2 (osteopenia), C1 (health). RESULTS:
      Significant differences were found between all the MCI groups due to their
      composition between fractures and non-fractures. C1 group (healthy) has less
      fractures women than C2 (Bonferroni p<0.001), C1 has less fractures than C3
      (Bonferroni p<0.001) and finally, C2 has less fractures than C3 (Bonferroni
      p<0.006). PMI and MI values were significantly lower in cases than in controls (U
      Mann-Whitney p<0.001). CONCLUSIONS: Panoramic radiomorphometrics mandibular
      indexes such as MCI, PMI, and MI, may be useful for identifying the population at
      higher risk for fracture. The relationship between panoramic index and
      osteoporosis remains unclear and further studies using fragility fracture as a
      real marker of osteoporosis are warranted to clarify the exact role and effect of
      one condition on the other and the corresponding clinical implications.

PMID- 24090926
TI  - Standardized incidence and trend of osteoporotic hip fracture in Polish women and
      men: a nine year observation.
AB  - BACKGROUND: Osteoporosis and its consequence of low trauma fracture represent a
      major health burden in aging population, because it results in increased
      morbidity, mortality and high health care costs. The number of hip fractures
      worldwide will approximately double by the year 2025 and more than triple by
      2050. The aim of the study was to assess the incidence and trends of osteoporotic
      hip fracture in women and men aged over 50 years in polish population. MATERIALS
      AND METHODS: Hospital records in population of 32,100 men and 39,984 women
      between January 1st, 2002 and December 31, 2010 with ICD-10 codes S72,0, S72,1
      and S72,2 (femoral neck, intertrochanteric, subtrochanteric, inter and
      subtrochanteric fracture) were included in analysis. RESULTS: The study revealed
      937 low energy hip fractures (240 in men 697 and in women). Systematic increase
      in rate over the study period, with the 44% in last year compared to 2002 year
      can be noticed. The increase was lowest in female (20.7%) than in male population
      (57.6%), and similarly was lowest in urban (27%) than in rural (67.7%)
      inhabitants. CONCLUSION: Concluding, the incidence of osteoporotic hip fracture
      in Polish men and women aged over 50 years is low, but the epidemiological
      picture is likely to change due to apparent aging of the population. Increasing
      trend of hip fracture incidence together with changes in age structure will
      result in an increased need for specialized care including several medical
      branches (GP, orthopedics, geriatrics, rehabilitation). Levels of evidence - IV.

PMID- 24090927
TI  - Innovation in midlife health and beyond.

PMID- 24090928
TI  - Resveratrol mainly stimulates the glycolytic ATP synthesis flux and not the
      mitochondrial one: a saturation transfer NMR study in perfused and isolated rat
      liver.
AB  - Our aim was to monitor the effects of resveratrol (RSV) on the respective
      contribution of glycolysis and oxidative phosphorylation on the unidirectional
      flux of ATP synthesis in whole isolated rat liver perfused with Krebs-Henseleit
      Buffer (KHB). The rate of tissular ATP supply was measured directly by monitoring
      the chemical exchange Pi toward ATP with saturation transfer (ST) (31)P nuclear
      magnetic resonance, a method applied for the first time for studying the effects
      of RSV. ST allows the measurement of the total cellular Pi->ATP chemical
      exchange; after specific inhibition of glycolysis with iodacetate, ST could
      provide the Pi->ATP flux issued from mitochondria. This latter was compared to
      mitochondrial ATP turn-over evaluated after chemical ischemia (CI), performed
      with specific inhibition (KCN) of oxidative phosphorylation, and measured by
      standard (31)P NMR spectroscopy. In controls (KHB alone), the apparent time
      constant (ks) of Pi exchange toward ATP as measured by ST was 0.48+/-0.04s(-1)
      leading to a total ATP synthesis rate of 37+/-3.9MUmolmin(-1)g(-1). KHB+RSV
      perfusion increased ks (+52%; p=0.0009 vs. KHB) leading to an enhanced rate of
      total ATP synthesis (+52%; p=0.01 vs. KHB). When glycolysis was previously
      inhibited in KHB, both ks and ATP synthesis flux dramatically decreased (-87% and
      -86%, respectively, p<0.0001 vs. KHB without inhibition), evidencing a collapse
      of Pi-to-ATP exchange. However, glycolysis inhibition in KHB+RSV reduced to less
      extent ks (-41%, p=0.0005 vs. KHB+RSV without inhibition) and ATP synthesis flux
      (-18%). Using the CI method in KHB and KHB+RSV, KCN addition after glycolysis
      inhibition induced a rapid fall to zero of the ATP content. The mitochondrial ATP
      turnover R(t0) and its time constant kd mito were similar in KHB (1.18+/
      0.19MUmolmin(-1)g(-1) and 0.91+/-0.13min(-1)) and KHB+RSV (1.36+/-0.26MUmolmin(
      1)g(-1) and 0.77+/-0.18min(-1)). Since mitochondrial ATP turnover was not
      increased by RSV, the stimulation of Pi-to-ATP exchange by RSV mainly reflected
      an increase in glycolytic ATP synthesis flux. Moreover, the maintenance by RSV of
      a high level of Pi-to-ATP exchange after glycolysis inhibition evidenced a
      protective effect of the polyphenol, in agreement with our previous hypothesis of
      a stimulation of substrate flux throughout the glycolysis 3-carbon step. 

PMID- 24090930
TI  - Review of mixed treatment comparisons in published systematic reviews shows
      marked increase since 2009.
AB  - OBJECTIVES: To identify and summarize published systematic reviews that report
      results of meta-analyses that combined direct and indirect comparisons. STUDY
      DESIGN AND SETTING: Narrative review of mixed treatment comparisons (MTCs)
      reported in systematic reviews of health interventions. MEDLINE, MEDLINE In
      Process, Embase, CINAHL, DARE, the Cochrane Database of Systematic Reviews, and
      SIGLE were searched for reviews published up to June 2012 in which a meta
      analysis had been conducted that combined direct and indirect comparisons among
      more than two interventions. RESULTS: Reviews reporting MTCs are difficult to
      identify when searching major databases. These databases offer no way to identify
      MTCs, and authors use various names when reporting them. Of the 201 eligible
      reviews identified, more than three-quarters had been published in full. MTC
      methods have been used to study a wide range of clinical topics. The reported use
      of these methods has increased rapidly since 2009, and results from MTCs are
      commonly used in health policy decisions, through the evidence considered in
      health technology assessments. CONCLUSION: In view of the increasing use of MTCs,
      indexing of this study type in databases and a consensus on terminology and
      standards for conduct and reporting would be timely.

PMID- 24090929
TI  - Interaction of Plasmodium falciparum knob-associated histidine-rich protein
      (KAHRP) with erythrocyte ankyrin R is required for its attachment to the
      erythrocyte membrane.
AB  - The malaria parasite Plasmodium falciparum exports a large number of proteins
      into the erythrocyte cytoplasm during the asexual intraerythrocytic stage of its
      life cycle. A subset of these proteins interacts with erythrocyte membrane
      skeletal proteins and grossly alters the structure and function of the membrane.
      Several of the exported proteins, such as PfEMP1, PfEMP3, RESA and KAHRP,
      interact with the preponderant erythrocyte skeleton protein, spectrin. Here we
      have searched for possible interaction of these four malaria proteins with
      another major erythrocyte skeleton protein, ankyrin R. We have shown that KAHRP,
      but none of the other three, binds to ankyrin R. We have mapped the binding site
      for ankyrin R to a 79-residue segment of the KAHRP sequence, and the reciprocal
      binding site for KAHRP in ankyrin R to a subdomain (D3) of the 89kDa ankyrin R
      membrane-binding domain. Interaction of intact ankyrin R with KAHRP was inhibited
      by the free D3 subdomain. When, moreover, red cells loaded with the soluble D3
      subdomain were infected with P. falciparum, KAHRP secreted by the
      intraerythrocytic parasite no longer migrated to the host cell membrane, but
      remained diffusely distributed throughout the cytosol. Our findings suggest a
      potentially important role for interaction of KAHRP with red cell membrane
      skeleton in promoting the adhesion of malaria-infected red cells to endothelial
      surfaces, a central element in the pathophysiology of malaria. 

PMID- 24090931
TI  - Opening windows into the cell: focused-ion-beam milling for cryo-electron
      tomography.
AB  - Cryo-electron tomography (CET) is ideally suited for bridging the resolution gap
      between molecular and cellular structural studies. However, CET is limited to a
      sample thickness under 500nm, which is thinner than most cells. Here, we review a
      method for preparing cells for CET using focused-ion-beam milling, a technique
      commonly used in materials science. Adapted to cryogenic conditions, FIB milling
      can be applied to various cell types to produce samples thin enough for CET that
      do not present the artefacts typical to other preparation techniques, for
      example, cryo-ultramicrotomy, effectively opening windows into intact cells.
      Samples can be produced routinely and reproducibly. The data obtained from CET
      can be used for structural studies in situ, or to do quantitative cell biology
      studies, in which cells can be observed at the molecular level under different
      physiological conditions. 

PMID- 24090932
TI  - Neural stem cell isolation from the whole mouse brain using the novel FABP7
      binding fluorescent dye, CDr3.
AB  - Methods for the isolation of live neural stem cells from the brain are limited
      due to the lack of well-defined cell surface markers and tools to detect
      intracellular markers. To date most methods depend on the labeling of
      extracellular markers using antibodies, with intracellular markers remaining
      inaccessible in live cells. Using a novel intracellular protein FABP7 (Fatty Acid
      Binding Protein-7) selective fluorescent chemical probe CDr3, we have
      successfully isolated high FABP7 expressing cells from the embryonic and adult
      mouse brains. These cells are capable of forming neurospheres in culture, express
      neural stem cell marker genes and differentiate into neurons, astrocytes and
      oligodendrocytes. Characterization of cells sorted with Aldefluor or antibodies
      against CD133 or SSEA-1 showed that the cells isolated by CDr3 exhibit a
      phenotype distinct from the cells sorted with conventional methods. FABP7
      labeling with CDr3 represents a novel method for rapid isolation of neural stem
      cells based on the expression of a single intracellular marker. 

PMID- 24090933
TI  - Heat shock instructs hESCs to exit from the self-renewal program through negative
      regulation of OCT4 by SAPK/JNK and HSF1 pathway.
AB  - Environmental factors affect self-renewal of stem cells by modulating the
      components of self-renewal networks. Heat shock, an environmental factor, induces
      heat shock factors (HSFs), which up-regulate stress response-related genes.
      However, the link of heat shock to self-renewal of stem cells has not been
      elucidated yet. Here, we present the direct link of heat shock to a core stem
      cell regulator, OCT4, in the self-renewal network through SAPK/JNK and HSF1
      pathway. We first showed that heat shock initiated differentiation of human
      embryonic stem cells (hESCs). Gene expression analysis revealed that heat shock
      increased the expression of many genes involved in cellular processes related to
      differentiation of stem cells. We then examined the effects of HSFs induced by
      heat shock on core self-renewal factors. Among HSFs, heat shock induced mainly
      HSF1 in hESCs. The HSF1 repressed the expression of OCT4, leading to the
      differentiation of hESCs and the above differentiation-related gene expression
      change. We further examined the effects of the upstream MAP (mitogen-activated
      protein) kinases of HSF1 on the repression of OCT4 expression by HSF1. Among the
      MAP kinases, SAPK/JNK controlled predominantly the repression of the OCT4
      expression by HSF1. The direct link of heat shock to the core self-renewal
      regulator through SAPK/JNK and HSF1 provides a fundamental basis for
      understanding the effect of heat and other stresses involving activation of HSF1
      on the self-renewal program and further controlling differentiation of hESCs in a
      broad spectrum of stem cell applications using these stresses. 

PMID- 24090934
TI  - Transplantation of mesenchymal stem cells for the treatment of liver diseases, is
      there enough evidence?
AB  - Mesenchymal stem cells or multipotent mesenchymal stromal cells (MSCs) have been
      extensively investigated in small animal models to treat both acute and chronic
      liver injuries. Mechanisms of action are not clearly elucidated but may include
      their ability to differentiate into hepatocyte-like cells, to reduce
      inflammation, and to enhance tissue repair at the site of injury. This approach
      is controversial and evidence in large animals is missing. Side effects of MSC
      infusion such as the contribution to a fibrotic process have been reported in
      experimental settings. Nevertheless, MSCs moved quickly from bench to bedside and
      over 280 clinical trials are registered, of which 28 focus on the treatment of
      liver diseases. If no severe side-effects were observed so far, long-term
      benefits remain uncertain. More preclinical data regarding mechanisms of action,
      long term safety and efficacy are warranted before initiating large scale
      clinical application. The proposal of this review is to visit the current state
      of knowledge regarding mechanisms behind the therapeutic effects of MSCs in the
      treatment of experimental liver diseases, to address questions about efficacy and
      risk, and to discuss recent clinical advances involving MSC-based therapies. 

PMID- 24090935
TI  - Preface: the liver in systemic disease.

PMID- 24090936
TI  - Mechanisms of liver involvement in systemic disease.
AB  - The liver may be injured during the course of many systemic diseases. The
      mechanisms of injury can be broadly divided into four pathways: vascular, toxic,
      immune, and hormonal. Vascular obstruction may be an early event but is also the
      late common pathway from all mechanisms. Despite the large number of possible
      initiating factors, the end results are few, including death of hepatocytes or
      cholangiocytes, leading to the stereotyped syndromes of acute liver failure, non
      cirrhotic portal hypertension, or cirrhosis. This small number of outcomes is a
      reflection of the few anatomic patterns that can be generated by microvascular
      obstruction. Vascular obstruction may occur by thrombosis, inflammation, or
      congestive injury. The innate immunity pathway is activated by endotoxin and
      other agents, leading to inflammatory infiltration, release of cytokines and
      reactive oxygen species, and necrosis. The adaptive immune pathway involves the
      generation of antibodies and antigen-specific cell-mediated attack on hepatic
      cells. Hormonal effects are principally involved when overnutrition leads to
      hyperinsulinemia followed by hepatocellular necrosis. 

PMID- 24090937
TI  - Hepatic changes in systemic infection.
AB  - Liver is an integral part of the host-defense mechanism and facilitates clearance
      of pathogenic organisms in systemic infection by modulating the immunological
      response. It undergoes several cellular and molecular changes resulting in the
      release of pro-inflammatory cytokines, which regulate various metabolic and
      immunological signalling pathways. Some of these changes are pathogen-specific
      and essential in determining the host response to systemic infection. However,
      alterations in the immunological homeostasis can adversely affect the liver and
      lead to hepatic dysfunction. This article focuses on these molecular and
      immunological changes that occur within the liver in response to extra-hepatic
      systemic infection and its consequences. 

PMID- 24090938
TI  - Liver in cardiopulmonary disease.
AB  - Hepatopulmonary syndrome (HPS) and portopulmonary hypertension (PoPH) are two
      fascinating and incompletely understood pulmonary vascular conditions seen in the
      setting of cirrhotic patients. Of the two HPS is more common and is primarily
      caused by pulmonary vasodilatation resulting in hypoxaemia and hyperdynamic
      circulation. PoPH is less common and conversely, pulmonary vasoconstriction and
      vascular remodelling occurs resulting in increased pulmonary vascular resistance.
      However, both conditions can co-exist and it is usually PoPH which develops in a
      patient with pre-existing HPS. Although these two pulmonary conditions are not
      common complications of chronic liver diseases, the treatment options are mainly
      limited to liver transplantation. Cirrhotic cardiomyopathy is closely related to
      haemodynamic changes in portal hypertension. The key features are normal cardiac
      pressures at rest, with reduced ability to compensate for physiological or
      iatrogenic stresses such as drug therapy or TIPSS. There is no effective therapy
      and outcomes after liver transplantation are variable. 

PMID- 24090940
TI  - Liver abnormalities in bowel diseases.
AB  - Liver abnormalities are often seen in bowel diseases. Whether these represent
      aspects of two separate diseases, or if one is causing the other, is not always
      easy to decide. Extraintestinal manifestations of inflammatory bowel disease
      (IBD) or coeliac disease are frequently observed. Of these extraintestinal
      manifestations, hepatic disorders are among the most common. Primary sclerosing
      cholangitis (PSC) and primary biliary cirrhosis are the most frequent hepatic
      disorders in IBD and coeliac disease, respectively. Genetic studies have lately
      elucidated the associations between IBD and PSC, but there is still a long way
      until we have complete understanding of the molecular aetiology and
      pathophysiology of these conditions. There is no curative treatment available for
      PSC, besides liver transplantation. Steatosis and cholelithiasis are also common
      in IBD, as are signs of hepatic injury due to IBD treatment. Less common liver
      abnormalities include liver abscesses, hepatic thromboembolic events,
      granulomatous liver disease and hepatic amyloidosis. 

PMID- 24090939
TI  - Liver in haematological disorders.
AB  - Prothrombotic haematological disorders, in particular myeloproliferative
      disorders, are identified in a significant proportion of patients with Budd
      Chiari syndrome and portal vein thrombosis (PVT). Multiple prothrombotic
      disorders may coexist. PVT is diagnosed in one fourth of patients with cirrhosis
      and is more common with advanced liver disease and hepatocellular carcinoma. PVT
      in cirrhosis can precipitate decompensation. Intrahepatic microthrombosis may
      play a role in the pathogenesis of hepatic fibrosis. Sinusoidal obstruction
      syndrome is usually a complication of myeloablative treatment before
      haematopoietic stem cell transplantation. Post-transplant lymphoproliferative
      disorders can complicate liver transplantation and are related to Epstein-Barr
      virus infection. Hepatitis B reactivation in patients receiving chemotherapy for
      haematological malignancies is very common without pre-emptive treatment, and can
      lead to liver failure. Liver involvement is common in primary haematological
      diseases, such as haemolytic anaemias, lymphomas and leukaemia. 

PMID- 24090941
TI  - Liver abnormalities in connective tissue diseases.
AB  - The liver is a lymphoid organ involved in the immune response and in the
      maintenance of tolerance to self molecules, but it is also a target of autoimmune
      reactions, as observed in primary liver autoimmune diseases (AILD) such as
      autoimmune hepatitis, primary biliary cirrhosis, and primary sclerosing
      cholangitis. Further, the liver is frequently involved in connective tissue
      diseases (CTD), most commonly in the form of liver function test biochemical
      changes with predominant cholestatic or hepatocellular patterns. CTD commonly
      affecting the liver include systemic lupus erythematosus, antiphospholypid
      syndrome, primary Sjogren's syndrome, systemic sclerosis, dermatomyositis,
      polimyositis, and anti-synthetase syndrome, while overlap syndromes between AILD
      and CTD may also be diagnosed. Although liver cirrhosis and failure are extremely
      rare in patients with CTD, unusual liver conditions such as nodular regenerative
      hyperplasia or Budd-Chiari syndrome have been reported with increasing frequency
      in patients with CTD. Acute or progressing liver involvement is generally related
      to viral hepatitis reactivation or to a concomitant AILD, so it appears to be
      fundamental to screen patients for HBV and HCV infection, in order to provide the
      ideal therapeutic regimen and avoid life-threatening reactivations. Finally, it
      is important to remember that the main cause of biochemical liver abnormalities
      in patients with CTD is a drug-induced alteration or coexisting viral hepatitis.
      The present article will provide a general overview of the liver involvement in
      CTD to allow rheumatologists to discriminate the most common clinical scenarios. 

PMID- 24090942
TI  - Liver abnormalities and endocrine diseases.
AB  - The liver and its pleotropic functions play a fundamental role in regulating
      metabolism, and is also an inevitable target of multiple metabolic disorders. The
      numerous and constant relationships and feedback mechanisms between the liver and
      all endocrine organs is reflected by the fact that an alteration of one
      oftentimes results in the malfunction of the other. Hypo- and hyperthyroidism are
      frequently associated with hepatic alterations, and thyroid diseases must be
      excluded in transaminase elevation of unknown cause. Drugs such as
      propylthiouracil, used in the treatment of hyperthyroidism, may induce liver
      damage, and other drugs such as amiodarone, carbamazepine, and several
      chemotherapeutic agents can lead to both thyroid and liver abnormalities. Liver
      diseases such as hepatitis, hepatocellular carcinoma, and cirrhosis may cause
      altered levels of thyroid hormones, and alcoholic liver disease, both due to the
      noxious substance ethanol as well as to the hepatic damage it causes, may be
      responsible for altered thyroid function. Both excess and insufficiency of
      adrenal function may result in altered liver function, and adrenocortical
      dysfunction may be present in patients with cirrhosis, especially during episodes
      of decompensation. Again an important player which affects both the endocrine
      system and the liver, alcohol may be associated with pseudo-Cushing syndrome. Sex
      hormones, both intrinsic as well as extrinsically administered, have an important
      impact on liver function. While oestrogens are related to cholestatic liver
      damage, androgens are the culprit of adenomas and hepatocellular carcinoma, among
      others. Chronic liver disease, on the other hand, has profound repercussions on
      sex hormone metabolism, inducing feminization in men and infertility and
      amenorrhoea in women. Lastly, metabolic syndrome, the pandemia of the present and
      future centuries, links the spectrum of liver damage ranging from steatosis to
      cirrhosis, to the array of endocrine alterations that are features of the
      syndrome, including insulin resistance, central obesity, and hyperlipidaemia.
      Clinical practice must integrally evaluate the effects of the intricate and tight
      relationship between the liver and the endocrine system, in order to better
      address all manifestations, complications, and prevent deterioration of one or
      the other organ-system. 

PMID- 24090943
TI  - Liver abnormalities in pregnancy.
AB  - Abnormalities of liver function (notably rise in alkaline phosphatase and fall in
      serum albumin) are common in normal pregnancy, whereas rise in serum bilirubin
      and aminotransferase suggest either exacerbation of underlying pre-existing liver
      disease, liver disease related to pregnancy or liver disease unrelated to
      pregnancy. Pregnant women appear to have a worse outcome when infected with
      Hepatitis E virus. Liver diseases associated with pregnancy include abnormalities
      associated hyperemesis gravidarum, acute fatty liver disease, pre-eclampsia,
      cholestasis of pregnancy and HELLP syndrome. Prompt investigation and diagnosis
      is important in ensuring a successful maternal and foetal outcome. In general,
      prompt delivery is the treatment of choice for acute fatty liver, pre-eclampsia
      and HELLP syndrome and ursodeoxycholic acid is used for cholestasis of pregnancy
      although it is not licenced for this indication. 

PMID- 24090944
TI  - Liver abnormalities in drug and substance abusers.
AB  - Drug and substance abuse remains a major medical problem. Alcohol use, abuse and
      dependence are highly prevalent conditions. Alcohol related liver disease can
      present as simple steatosis, steatohepatitis, alcoholic hepatitis or liver
      cirrhosis. Paracetamol hepatotoxicity secondary to accidental or deliberate
      overdose is another common problem. While the adverse cardiovascular,
      neurological, renal and psychiatric consequences of various illicit substance
      abuses are widely studied and publicized, less attention has been directed
      towards possible hepatotoxic effects. Illicit drug abuse can cause a range of
      liver abnormalities ranging from asymptomatic derangement of liver function tests
      to fulminant hepatic failure. This article reviews the epidemiology, risk
      factors, clinical manifestations, pathogenesis, investigations, management and
      prognostic factors of alcohol related liver disease and paracetamol
      hepatotoxicity as well as the current knowledge pertaining to hepatotoxicity of
      the more commonly used illicit substances including cannabis, amphetamine type
      stimulants, cocaine, khat chewing and complementary and alternate medicine. 

PMID- 24090945
TI  - Liver abnormalities in the immunosuppressed.
AB  - The immunosuppressed state may arise due to medical illness or drug therapy,
      which can result in a diverse array of liver derangements. This article discusses
      the commonly-encountered immunosuppressed conditions and the associated specific
      liver diseases. Due to the frequency of blood-borne viral disease globally, viral
      hepatitis (hepatitis B and C) during chemotherapy, transplantation and the
      increasingly utilised biological therapies for autoimmune disorders is discussed.
      An overview of human immunodeficiency virus co-infection with hepatitis B and C
      is provided. This article aims to highlight the variety of liver diseases which
      can occur in clinically relevant, particularly iatrogenic, immunosuppressed
      conditions, and summarise learning and practice points for clinicians.
      Recognition and prevention of viral liver disease is crucial and early
      involvement of experts prior to administration of immunosuppressive therapy is
      advised. 

PMID- 24090946
TI  - Liver disease and malnutrition.
AB  - Patients with hepatic disorders are exceptionally vulnerable to developing
      malnutrition because of the key role played by the liver in regulating the
      nutritional state and the energy balance. Moreover, the presence of chronic liver
      disorders could reduce the appetite and thus influence the nutrient intake. Poor
      nutritional status has been shown in various patient groups with hepatic
      disorders, and particularly in patients with alcoholic cirrhosis who are at high
      nutritional risk. It is well established that malnourished patients with liver
      diseases generally have a higher risk of developing adverse clinical outcomes and
      increased healthcare costs. Nutrition screening with the Subjective Global
      Assessment and anthropometric measurements are an important first step in the
      early identification of malnutrition and initiates the whole nutrition care
      process. It is therefore important for appropriate nutrition policies and
      protocols to be implemented so that all patients with chronic liver diseases are
      monitored closely from a nutritional standpoint. Early and evidence-based
      nutritional interventions are eagerly needed to minimize the nutritional decline
      associated with chronic liver disorders and ultimately improve the prognosis of
      such patients. This review includes a comprehensive analysis of methods to
      identify malnutrition in patients with chronic liver diseases as well as the
      extent and impact of the malnutrition problem in selected patient populations. 

PMID- 24090947
TI  - Psychogenic paroxysmal movement disorders--clinical features and diagnostic
      clues.
AB  - BACKGROUND: The diagnosis of psychogenic paroxysmal movement disorders (PPMD) can
      be challenging, in particular their distinction from the primary paroxysmal
      dyskinesias (PxD) remains difficult. METHODS: Here we present a large series of
      26 PPMD cases, describe their characteristics, contrast them with primary PxD and
      focus on their distinguishing diagnostic features. RESULTS: Mean age at onset was
      38.6 years, i.e. much later than primary PxD. Women were predominantly affected
      (73%). Most subjects (88.4%) had long attacks, and unlike primary PxD there was a
      very high within-subject variability for attack phenomenology, duration and
      frequency. Dystonia was the most common single movement disorder presentation,
      but 69.2% of the patients had mixed or complex PxD. In 50% of PPMD cases attack
      triggers could be identified but these were unusual for primary PxD. 42.3% of
      patients employed unusual strategies to alleviate or stop the attacks. Response
      to typical medication used for primary PxD was poor. Precipitation of the
      disorder due to physical or emotional life events and stressors were documented
      in 57.6% and 65.3% of the cases respectively. Additional interictal psychogenic
      signs were documented in 34.6% and further medically unexplained somatic symptoms
      were present in 50% of the cases. 19.2% of patients had a comorbid organic
      movement disorder and 26.9% had pre-existing psychiatric comorbidities.
      CONCLUSION: Although the phenotypic presentation of PPMD can be highly diverse,
      certain clinical characteristics help in distinguishing this condition from the
      primary forms of PxD. Recognition is important as multidisciplinary treatment
      approaches led to significant improvement in most cases.

PMID- 24090948
TI  - Impulsive and compulsive behaviors among Danish patients with Parkinson's
      disease: prevalence, depression, and personality.
AB  - INTRODUCTION: Dopaminergic medication administered to ameliorate motor symptoms
      of Parkinson's disease is associated with impulse control disorders, such as
      pathological gambling, hypersexuality, compulsive buying, and binge eating.
      Studies indicate a prevalence of impulse control disorders in Parkinson's disease
      of 6-16%. OBJECTIVE: To estimate the prevalence of impulsive and compulsive
      behaviors among Danish patients with Parkinson's disease and to explore the
      relation of such behavioral disorders to depression and personality. METHODS: 490
      patients with Parkinson's disease (303 males), identified through the National
      Danish Patient Registry, were evaluated with: 1) the Questionnaire for Impulsive
      Compulsive Disorders in Parkinson's Disease; 2) the Geriatric Depression Scale;
      and 3) the NEO-Personality Inventory. RESULTS: 176 (35.9%) patients reported
      impulsive and compulsive behaviors sometime during Parkinson's disease (current
      symptoms in 73, 14.9%). Hereof, 114 (23.3%) reported multiple behavioral
      symptoms. Patients with behavioral symptoms were significantly younger, were
      younger at PD onset, had longer disease duration, displayed more motor symptoms,
      and received higher doses of dopaminergic medication than patients without
      behavioral symptoms. Furthermore, they reported significantly more depressive
      symptoms and scored significantly higher on neuroticism and lower on both
      agreeableness and conscientiousness than patients without behavioral symptoms.
      CONCLUSION: A history of impulsive and compulsive behaviors are common in Danish
      patients with Parkinson's disease and have clinical correlates that may allow
      identification of patients at risk for developing these behaviors.

PMID- 24090949
TI  - Dopaminergic modulation of motor coordinaton in Parkinson's disease.
AB  - BACKGROUND: We applied the idea of synergies and the framework of the
      uncontrolled manifold hypothesis to explore the effects of dopamine replacement
      therapy on finger interaction and coordination in patients with early-stage
      Parkinson's disease (PD). METHODS: Eight patients performed single-finger and
      multi-finger force production tasks with both the dominant and non-dominant hand
      before (off-drug) and after (on-drug) taking their dopaminergic medications.
      Synergy indices were defined as co-varied adjustments of commands to fingers that
      stabilized the total force produced by the hand. RESULTS: PD patients showed
      significantly lower maximal finger forces off-drug compared to the on-drug
      condition, while indices of finger individuation (enslaving) were unchanged. The
      synergy indices were weaker during steady-state force production off-drug
      compared to on-drug. Anticipatory adjustments of synergies prior to the quick
      force pulse initiation were delayed and reduced off-drug as compared to the on
      drug condition. These drug effects were observed in both the symptomatic and
      asymptomatic hands of the patients whose symptoms were limited to one side of the
      body. CONCLUSIONS: The study demonstrates dopaminergic modulation of motor
      coordination in PD and supports that the analysis of different components of
      multi-finger synergies offers a set of indices sensitive to the effects of
      dopamine replacement therapy in early-stage PD. The results suggest an important
      role of the basal ganglia in synergy formation and in feed-forward synergy
      adjustments. Future studies using these methods may yield more objective,
      quantitative biomarker(s) of motor coordination impairments in PD, and better
      understanding of subcortical involvement in the neural control of natural
      actions.

PMID- 24090950
TI  - The expression of angiotensin-converting enzyme 2-angiotensin-(1-7)-Mas receptor
      axis are upregulated after acute cerebral ischemic stroke in rats.
AB  - There is now unequivocal evidence that the angiotensin-converting enzyme 2(ACE2)
      Ang-(1-7)-Mas axis is a key component of the renin-angiotensin system (RAS)
      cascade, which is closely correlated with ischemic insult occurrence. Our
      previous studies demonstrated that the Ang-(1-7), was an active member of the
      brain RAS. However, the ACE2-Ang-(1-7)-Mas axis expression after cerebral
      ischemic injury are currently unclear. In the present study, we investigated the
      time course of ACE2-Ang-(1-7) and Mas receptor expression in the acute stage of
      cerebral ischemic stroke. The content of Ang-(1-7) in ischemic tissues and blood
      serum was measured by specific EIA kits. Real-time PCR and western blot were used
      to determine messenger RNA (mRNA) and protein levels of the ACE2 and Mas. The
      cerebral ischemic lesion resulted in a significant increase of regional cerebral
      and circulating Ang-(1-7) at 6-48 h compared with sham operation group following
      focal ischemic stroke (12h: 7.276+/-0.320 ng/ml vs. 2.466+/-0.410 ng/ml, serum;
      1.024+/-0.056 ng/mg vs. 0.499+/-0.032, brain) (P<0.05). Both ACE2 and Mas
      expression were markedly enhanced compared to the control in the ischemic tissues
      (P<0.05). Mas immunopositive neurons were also seen stronger expression in the
      ischemic cortex (19.167+/-2.858 vs. 7.833+/-2.483) (P<0.05). The evidence
      collected in our present study will indicate that, ACE2-Ang-(1-7)-Mas axis are
      upregulated after acute ischemic stroke and would play a pivotal role in the
      regulation of acute neuron injury in ischemic cerebrovascular diseases.

PMID- 24090951
TI  - Physical activity, glycemic control, and diabetic peripheral neuropathy: a
      national sample.
AB  - To determine if physical activity and/or blood glycohemoglobin (HbA1c) are
      associated with the prevalence of peripheral neuropathy (PN) in a representative
      population of diabetics. Three hundred thirty-nine diabetic participants (40-85
      yrs) taking part in 2003-2004 National Health and Nutrition Examination Survey
      were studied. Participants were defined as having peripheral neuropathy if
      examination determined >=1 insensate area in either foot. Moderate-to-vigorous
      physical activity (MVPA) was objectively-measured using accelerometry. After
      adjustments, MVPA was not significantly associated with PN (OR=1.16; 95% CI: 0.48
      2.78), nor was HbA1c (OR=0.55; 95% CI: 0.28-1.04). However, there was evidence of
      statistical interaction (OR=0.24; 95% CI: 0.06-0.87) between MVPA and HbA1c
      status, showing that diabetics engaging in higher levels of MVPA and having
      normal HgbA1c levels were less likely to have PN than what would be expected
      based on the individual effects of MVPA and HbA1c alone. Although MVPA was not
      directly associated with PN, these findings suggest that proper physical
      activity, coupled with good glycemic control, is associated with less neuropathy.
      Future longitudinal studies are required to evaluate whether physical activity
      and improved glycemic control may help prevent or slow the progression of
      diabetic end-organ damage, particularly diabetic neuropathy.

PMID- 24090953
TI  - Clinician-scientists in ophthalmology revisited.

PMID- 24090952
TI  - Galectin-3: a new biomarker for the diagnosis, analysis and prognosis of acute
      and chronic heart failure.
AB  - Heart failure constitutes an important medical, social and economic problem. The
      prevalence of heart failure is estimated as 2-3% of the adult population and
      increases with age, despite the scientific progress of the past decade,
      especially the emergence of natriuretic peptides, which have been widely used as
      reliable markers for diagnostic and prognostic evaluation. Identification of new
      reliable markers for diagnosis, analysis, prognosis of mortality and prevention
      of hospitalization is still necessary. Galectin-3 is a soluble beta-galactoside
      binding protein secreted by activated macrophages. Its main action is to bind to
      and activate the fibroblasts that form collagen and scar tissue, leading to
      progressive cardiac fibrosis. Numerous experimental studies have shown the
      important role of galectin-3 in cardiac remodelling due to fibrosis, independent
      of the fibrosis aetiology. Galectin-3 is significantly increased in chronic heart
      failure (acute or non-acute onset), independent of aetiology. Some clinical
      studies have confirmed the predictive value of galectin-3 in all-cause mortality
      in patients with heart failure. In our review, we aim to analyse the role of
      galectin-3 in the development of heart failure, its value in screening and
      clinical decision making and its possible predictive application in follow-up as
      a "routine" test in an addition to established biomarkers, such as B-type
      natriuretic peptide and N-terminal prohormone of B-type natriuretic peptide. 

PMID- 24090954
TI  - Measuring contrast sensitivity using the M&S Smart System II versus the Pelli
      Robson chart.

PMID- 24090955
TI  - Liquid nitrogen cryotherapy of pterygia.

PMID- 24090956
TI  - Author reply: To PMID 23062647.

PMID- 24090957
TI  - Clear lens extraction for angle closure.

PMID- 24090958
TI  - Author reply: To PMID 22986111.

PMID- 24090959
TI  - AAO Task Force on Genetic Testing.

PMID- 24090960
TI  - Author reply: To PMID 22944025.

PMID- 24090961
TI  - Oral contraceptive use and cancer: final report from the Oxford-Family Planning
      Association contraceptive study.
AB  - BACKGROUND: This analysis provides the final results on cancer incidence in
      relation to oral contraceptive (OC) use from the Oxford-Family Planning
      Association (Oxford-FPA) contraceptive study, which closed at the end of 2010. An
      additional 6 years of observation have been added since our last report and there
      has been an increase in the numbers of cancers of over 50% at seven of the sites
      considered. STUDY DESIGN: The Oxford-FPA study includes 17032 women aged 25-39
      years recruited from 1968 to 1974 at contraceptive clinics in England and
      Scotland. These women were using OCs, a diaphragm or an intrauterine device.
      Information about cancer incidence among them has been collected from recruitment
      until closure of the study. RESULTS: OC use was not related to nonreproductive
      cancer. Breast cancer findings (1087 cases) were entirely negative; the rate
      ratio (RR) comparing ever users of OCs with never users was 1.0 [95% confidence
      interval (CI): 0.9-1.1]. Only two cases of cervical cancer have been added since
      our last report (total: 61 cases); the RR comparing ever use with never use is
      now 3.4 (95% CI: 1.6-8.9). The risk of this disease increases sharply with
      duration of OC use and declines steadily with interval since last OC use. OC use
      protects against both uterine body cancer (124 cases) and ovarian cancer (143
      cases). The RRs comparing ever use with never use were 0.5 (95% CI: 0.3-0.7) and
      0.5 (95% CI: 0.4-0.7), respectively. Protection against both these cancers
      increased with duration of OC use and waned with interval since last use, but an
      effect was still present 28 or more years after discontinuation. CONCLUSIONS: In
      our study, OC use had no effect on nonreproductive cancers or on breast cancer.
      The risk of cervical cancer was increased and that of uterine body cancer and
      ovarian cancer was decreased by OC use. All these effects increased with duration
      of use and declined with interval since last use. The beneficial effects of OC
      use on cancer outweighed the adverse effects. These findings should reassure
      older women who used OCs in the past.

PMID- 24090962
TI  - Neuroprotective effects of swimming training in a mouse model of Parkinson's
      disease induced by 6-hydroxydopamine.
AB  - Parkinson's disease (PD) is characterized by progressive dopamine (DA) depletion
      in the striatum. Exercise has been shown to be a promising non-pharmacological
      approach to reduce the risk of neurodegeneration diseases. This study was
      designed to investigate the potential neuroprotective effect of swimming training
      (ST) in a mouse model of PD induced by 6-hydroxydopamine (6-OHDA) in mice. The
      present study demonstrated that a 4-week ST was effective in attenuating the
      following impairments resulting from 6-OHDA exposure: (i) depressive-like
      behavior in the tail suspension test; (ii) increase in the number of falls in the
      rotarod test; (iii) impairment on long-term memory in the object recognition
      test; (iv) increase of the reactive species and interleukin 1-beta (IL-1beta)
      levels; (v) inhibition of the glutathione peroxidase (GPx) activity; (vi) rise of
      the glutathione reductase (GR) and glutathione S-transferase (GST) activities and
      vii) decrease of DA, homovanillic acid (HVA) and 3,4-dihydroxyphenylacetic acid
      (DOPAC) levels. The mechanisms involved in this study are the modulation of GPx,
      GR and GST activities as well as IL-1beta level in a PD model induced by 6-OHDA,
      protecting against the decrease of DA, DOPAC and HVA levels in the striatum of
      mice. These findings reinforce that one of the effects induced by exercise on
      neurodegenerative disease, such as PD, is due to antioxidant and anti
      inflammatory properties. We suggest that exercise attenuates cognitive and motor
      declines, depression, oxidative stress, and neuroinflammation induced by 6-OHDA
      supporting the hypothesis that exercise can be used as a non-pharmacological tool
      to reduce the symptoms of PD. 

PMID- 24090963
TI  - BIG1, a brefeldin A-inhibited guanine nucleotide-exchange protein regulates
      neurite development via PI3K-AKT and ERK signaling pathways.
AB  - The elongation of neuron is highly dependent on membrane trafficking. Brefeldin A
      (BFA)-inhibited guanine nucleotide-exchange protein 1 (BIG1) functions in the
      membrane trafficking between the Golgi apparatus and the plasma membrane. BFA, an
      uncompetitive inhibitor of BIG1 can inhibit neurite outgrowth and polarity
      development. In this study, we aimed to define the possible role of BIG1 in
      neurite development and to further investigate the potential mechanism. By
      immunostaining, we found that BIG1 was extensively colocalized with
      synaptophysin, a marker for synaptic vesicles in soma and partly in neurites. The
      amount of both protein and mRNA of BIG1 were up-regulated during rat brain
      development. BIG1 depletion significantly decreased the neurite length and
      inhibited the phosphorylation of phosphatidylinositide 3-kinase (PI3K) and
      protein kinase B (AKT). Inhibition of BIG1 guanine nucleotide-exchange factor
      (GEF) activity by BFA or overexpression of the dominant-negative BIG1 reduced
      PI3K and AKT phosphorylation, indicating regulatory effects of BIG1 on PI3K-AKT
      signaling pathway is dependent on its GEF activity. BIG1 siRNA or BFA treatment
      also significantly reduced extracellular signal-regulated kinase (ERK)
      phosphorylation. Overexpression of wild-type BIG1 significantly increased ERK
      phosphorylation, but the dominant-negative BIG1 had no effect on ERK
      phosphorylation, indicating the involvement of BIG1 in ERK signaling regulation
      may not be dependent on its GEF activity. Our result identified a novel function
      of BIG1 in neurite development. The newly recognized function integrates the
      function of BIG1 in membrane trafficking with the activation of PI3K-AKT and ERK
      signaling pathways which are critical in neurite development. 

PMID- 24090964
TI  - Movement strategies and sensory reweighting in tandem stance: differences between
      trained tightrope walkers and untrained subjects.
AB  - Does skill with a difficult task, such as tightrope walking, lead to improved
      balance through altered movement strategies or through altered weighting of
      sensory inputs? We approached this question by comparing tandem stance (TS) data
      between seven tightrope walkers and 12 untrained control subjects collected under
      different sensory conditions. All subjects performed four TS tasks with eyes open
      or closed, on a normal firm or foam surface (EON, ECN, EOF, ECF); tightrope
      walkers were also tested on a tightrope (EOR). Head, upper trunk and pelvis
      angular velocities were measured with gyroscopes in pitch and roll. Power
      spectral densities (PSDs) ratios, and transfer function gains (TFG) between these
      body segments were calculated. Center of mass (CoM) excursions and its virtual
      time to contact a virtual base of support boundary (VTVBS) were also estimated.
      Gain nonlinearities, in the form of decreased trunk to head and trunk to pelvis
      PSD ratios and TFGs, were present with increasing sensory task difficulty for
      both groups. PSD ratios and TFGs were less in trained subjects, though, in
      absolute terms, trained subjects moved their head, trunk, pelvis and CoM faster
      than controls, and had decreased VTVBS. Head roll amplitudes were unchanged with
      task or training, except above 3Hz. CoM amplitude deviations were not less for
      trained subjects. For the trained subjects, EOR measures were similar to those of
      ECF. Training standing on a tightrope induces a velocity modification of the same
      TS movement strategy used by untrained controls. More time is spent exploring the
      limits of the base of support with an increased use of fast trunk movements to
      control balance. Our evidence indicates an increased reliance on neck and pelvis
      proprioceptive inputs. The similarity of TS on foam to that on the tightrope
      suggests that the foam tasks are useful for effective training of tightrope
      walking. 

PMID- 24090965
TI  - Adsorption of uranium (VI) from aqueous solution using a novel graphene oxide
      activated carbon felt composite.
AB  - Graphene oxide(GO)-activated carbon felt(ACF)(GO-ACF) composite was prepared by
      an electrophoretic deposition and subsequent thermal annealing. The structures of
      GO and GO-ACF were characterized by FT-IR, Raman spectra and XPS. The adsorption
      capacities for U(VI) from aqueous solution of ACF and GO-ACF were compared. The
      essential factors affected U(VI) adsorption such as initial pH, contact time and
      temperature were investigated. The adsorption is highly dependent on the solution
      pH. In addition, the adsorption isotherm and thermodynamics were investigated.
      The adsorptions of U(VI) from aqueous solution on GO-ACF were fitted to the
      Langmuir and, Freundlich adsorption isotherms. The adsorption of U(VI) could be
      well-described by Langmuir. The adsorption of U(VI) on ACF is remarkably improved
      by GO covalently bonding with ACF. The maximum sorption capacity of GO-ACF for
      U(VI) was evaluated to be 298 mg/g at pH 5.5, much higher than that of ACF (173
      mg/g), suggesting the carboxyl functional groups of GO-ACF playing important
      roles in the sorption. Thermodynamic parameters further show that the sorption is
      an endothermic and spontaneous process. GO-ACF is a powerful promising sorbent
      for the efficient removal of U(VI) from aqueous solutions.

PMID- 24090966
TI  - Multi-drug-resistant, non-fermenting, gram-negative bacilli in neonatal sepsis in
      Kolkata, India: a 4-year study.
AB  - BACKGROUND: Non-fermenting gram-negative bacilli (NFGNB) are an emerging problem
      in neonatal sepsis. A major concern is multi-drug resistance which severely
      limits treatment options. AIMS AND OBJECTIVES: A retrospective observational
      study was conducted to analyse the role of non-fermenters in neonatal sepsis over
      a 4-year period, the factors leading to this trend and the pattern of antibiotic
      resistance. METHODS: Demographic and clinical data were collected for all
      neonates with blood culture-positive sepsis during the study period, January 2007
      to December 2010. RESULTS: Blood cultures were positive in 186 (13%) of 1402
      neonates, in 44 (32.1%) of whom the cause was NFGNB. Acinetobacter spp was the
      most common organism (n = 30). Infection by NFGNB showed a steady increase
      (P<0.0001), and was fairly evenly distributed between early- and late-onset
      sepsis. The infection rate was significantly higher in inborn neonates (P = 0.04)
      and those delivered vaginally (P = 0.002). Multi-drug resistance (MDR) occurred
      in 50% and carbapenem resistance in 30% of Acinetobacter spp isolates. In five
      cases there was panresistance of Acinetobacter spp to all antibiotics tested.
      CONCLUSION: The trend of increasing numbers of cases of NFGNB in neonatal sepsis
      compounded by MDR is of great concern. It is necessary to administer antibiotics
      judiciously, strengthen surveillance and laboratory services in neonatal
      intensive care units, and re-evaluate treatment guidelines for management of
      infection by these organisms.

PMID- 24090967
TI  - Identification and function of two myeloid differentiation factor 88 variants in
      triangle-shell pearl mussel (Hyriopsis cumingii).
AB  - Myeloid differentiation factor 88 (MyD88) is a universal and essential adapter
      protein that participates in the activation of the Toll-like receptor
      (TLR)/interleukin-1 receptor-mediated signaling pathway. In this study, two MyD88
      genes (HcMyD88-1 and HcMyD88-2) were identified from triangle-shell pearl mussel
      (Hyriopsis cumingii). Both HcMyD88-1 and HcMyD88-2 proteins were determined to
      have a death domain at the N-terminal and a TIR domain at the C-terminal. Both
      HcMyD88-1 and HcMyD88-2 genes were mainly expressed in the hepatopancreas of
      healthy mussels. HcMyD88-1 and HcMyD88-2 slightly responded to Gram-negative
      bacterial challenge. Upon bacterial challenge with Gram-positive Staphyloccocus
      aureus, HcMyD88-1 and HcMyD88-2 transcription levels remarkably increased at 2
      and 6h, respectively. Overexpression of HcMyD88-1 and HcMyD88-2 proteins in
      Drosophila Schneider 2 cells led to the activation of antimicrobial peptide
      genes. These results indicated that HcMyD88-2 had higher activity than HcMyD88-1
      during the activation of attacin A, drosomycin, and metchnikowin genes,
      suggesting that HcMyD88 genes may play a role in antibacterial innate immune
      defense.

PMID- 24090968
TI  - C. luteola infection in paediatrics: description of a rare neonatal case and
      review of the literature.
AB  - Chryseomonas luteola is a gram-negative microorganism that has rarely been
      reported as a human bacterial pathogen. Few cases are described in the literature
      and these mostly involve patients with health or indwelling disorders. Clinical
      infections in reported cases showed septicaemia, meningitis, peritonitis,
      endocarditis and ulcer infections. In the present paper, we describe a clinical
      case with neonatal onset recently observed in our ward and a review of the
      literature. 

PMID- 24090969
TI  - Can transcutaneous bilirubinometry safely guide phototherapy treatment of
      neonatal jaundice in Malawi?
AB  - OBJECTIVES: To assess the correlation between total serum bilirubin (TSB) and
      transcutaneous bilirubin (TcB) values in Malawian newborn infants, and to
      investigate whether TcB can be used safely to guide phototherapy treatment in the
      absence of TSB results. METHODS: 128 newborn jaundiced infants were studied in
      the neonatal nursery at Queen Elizabeth Central Hospital, Blantyre. Paired TSB
      and TcB measurements (from forehead and sternum) were compared using the linear
      regression and Bland-Altman methods. Clinical decisions based on TcB results were
      compared with those based on 'gold standard' TSB results. RESULTS: For infants
      not under phototherapy, the lowest TcB reading (from forehead or sternum) gave
      the strongest correlation with TSB: r = 0.83 for term infants and r = 0.71 for
      premature infants. For infants undergoing phototherapy, the highest TcB reading
      gave the strongest correlation with TSB: r = 0.66 for term infants and r = 0.71
      for premature infants. TcB values overestimated the degree of jaundice. For
      infants not under phototherapy, the mean (SD) bias and imprecision of TcB was 25
      (72) MUmol/L for term infants and 37 (73) MUmol/L for premature infants. For
      infants under phototherapy, the mean bias and imprecision was 30 (79) MUmol/L for
      term infants and 44 (77) MUmol/L for premature infants. For infants not under
      phototherapy, using the lowest TcB reading to guide treatment decisions (n = 167)
      had good sensitivity (91%) and specificity (90%). For infants undergoing
      phototherapy, using the highest TcB reading to guide treatment decisions (n =
      129) had good sensitivity (94%), but lower specificity (36%). CONCLUSIONS: TcB
      can be used to safely guide phototherapy treatment in a resource-poor setting.

PMID- 24090970
TI  - New non-alcoholic formulation for hand disinfection.
AB  - Hand washing is considered as the single most important strategy to prevent
      infections. World health organization (WHO) defines hand hygiene as a primary
      issue of personal care with particular reference to hospital personnel and health
      facility workers. In this work, we investigated a new combination for hand
      disinfection as an alternative to alcohol-based and chlorhexidine products. The
      new combination of 5-pyrrolidone-2-carboxylic acid (PCA) and copper sulphate
      pentahydrate (CS) was tested upon different bacterial species that normally
      colonize hands, including Staphylococcus aureus, methicillin resistant S. aureus
      (MR S. aureus), Staphylococcus epidermidis, multidrug resistant S. epidermidis
      (MDR S. epidermidis), Streptococcus pyogenes, Streptococcus agalactiae,
      Escherichia coli, Candida albicans and three clinical isolates: MR S. aureus, MDR
      S. epidermidis, and an E. coli strain. Minimal inhibitory concentrations (MICs),
      Minimal bactericidal concentrations (MBCs), fractional inhibitory concentration
      (FIC) indices, and fractional bactericidal concentration (FBC) indices were
      evaluated. Ethanol 70% V/V, isopropanol 60% V/V, and 4% w/V chlorhexidine
      solution were used as reference hand disinfectants. Copper sulphate pentahydrate
      was very effective against all tested microorganisms: The MIC and MBC for CS
      ranged from 781 mg/l against S. pyogenes to 12500 mg/l against E. coli strains
      and C. albicans. In addition, PCA exhibited a good antimicrobial activity, in
      particular, against S. pyogenes and S. agalactiae. The combination of CS and PCA
      showed a strong synergistic effect and all FIC indices were <=0.500. The
      combination of CS and PCA were more effective than ethanol 70% V/V and
      isopropanol 60% V/V. In addition to antimicrobial activity, the new formulation
      possesses peculiar features such as residual activity and moisturizing effect.
      This work identifies a new strategy for hand disinfection. 

PMID- 24090971
TI  - Assessment of hypersensitivity reactions in patients receiving carbapenem
      antibiotics who report a history of penicillin allergy.
AB  - BACKGROUND: The use of carbapenem antibacterials in patients with a claimed
      history of penicillin allergy is somewhat controversial. This study aimed to
      examine the rates of presumed hypersensitivity reactions in a large cohort of
      patients receiving carbapenem antibiotics. METHODS: A retrospective chart review
      was performed on all adult patients who received a carbapenem in a teaching
      hospital from June 2011 to June 2012. Information procured included listed
      penicillin allergy and reaction if known, type of carbapenem received, and any
      allergic reaction during that admission. RESULTS: Nine-hundred and fifty eight
      patients who received a carbapenem antimicrobial were reviewed. Five patients
      developed a presumed reaction to carbapenem: one in the penicillin allergy group
      and four in the non-allergic group. There were no statistical or numerical
      differences in rates of reaction between the two groups. CONCLUSION: Patients
      with a claimed history of penicillin allergy were not more likely to develop a
      presumed hypersensitivity reaction to a carbapenem compared to those who did not
      claim such an allergy.

PMID- 24090972
TI  - Should the dimensions of brachytherapy seeds be altered?

PMID- 24090973
TI  - Impact of delineation uncertainties on dose to organs at risk in CT-guided
      intracavitary brachytherapy.
AB  - PURPOSE: This study quantifies the inter- and intraobserver variations in
      contouring the organs at risk (OARs) in CT-guided brachytherapy (BT) for the
      treatment of cervical carcinoma. The dosimetric consequences are reported in
      accordance with the current Gynecological Groupe Europeen de
      Curietherapie/European Society for Therapeutic Radiology and Oncology guidelines.
      METHODS AND MATERIALS: A CT planning study of 8 consecutive patients undergoing
      image-guided BT was conducted. The bladder, rectum, and sigmoid were contoured by
      five blinded observers on two identical anonymized scans of each patient. This
      provided 80 data sets for analysis. Dosimetric parameters analyzed were D0.1 cc,
      D1 cc, and D2 cc. The mean volume of each OAR was calculated. These endpoints
      were compared between and within the observers. The CT image sets from all
      patients were evaluated qualitatively. RESULTS: The interobserver coefficient of
      variation for reported D2 cc was 13.2% for the bladder, 9% for the rectum, and
      19.9% for the sigmoid colon. Unlike the variation seen in bladder and rectal
      contours, which differed largely in localization of the organ walls on individual
      slices, sigmoid colon contours demonstrated large differences in anatomic
      interpretation. CONCLUSIONS: Variation in recorded D2 cc to the bladder and
      rectum is comparable with the previous published results. Inter- and
      intraphysician variations in reported D2 cc is high for the sigmoid colon,
      reflecting varying interpretation of sigmoid colon anatomy. Variation in
      delineation of the OARs may influence treatment optimization and is a potential
      source of uncertainty in the image-guided BT planning and delivery process.

PMID- 24090974
TI  - The HIF1A functional genetic polymorphism at locus +1772 associates with
      progression to metastatic prostate cancer and refractoriness to hormonal
      castration.
AB  - The hypoxia inducible factor 1 alpha (HIF1a) is a key regulator of tumour cell
      response to hypoxia, orchestrating mechanisms known to be involved in cancer
      aggressiveness and metastatic behaviour. In this study we sought to evaluate the
      association of a functional genetic polymorphism in HIF1A with overall and
      metastatic prostate cancer (PCa) risk and with response to androgen deprivation
      therapy (ADT). The HIF1A +1772 C>T (rs11549465) polymorphism was genotyped, using
      DNA isolated from peripheral blood, in 1490 male subjects (754 with prostate
      cancer and 736 controls cancer-free) through Real-Time PCR. A nested group of
      cancer patients who were eligible for androgen deprivation therapy was followed
      up. Univariate and multivariate models were used to analyse the response to
      hormonal treatment and the risk for developing distant metastasis. Age-adjusted
      odds ratios were calculated to evaluate prostate cancer risk. Our results showed
      that patients under ADT carrying the HIF1A +1772 T-allele have increased risk for
      developing distant metastasis (OR, 2.0; 95%CI, 1.1-3.9) and an independent 6-fold
      increased risk for resistance to ADT after multivariate analysis (OR, 6.0; 95%CI,
      2.2-16.8). This polymorphism was not associated with increased risk for being
      diagnosed with prostate cancer (OR, 0.9; 95%CI, 0.7-1.2). The HIF1A +1772 genetic
      polymorphism predicts a more aggressive prostate cancer behaviour, supporting the
      involvement of HIF1a in prostate cancer biological progression and ADT
      resistance. Molecular profiles using hypoxia markers may help predict clinically
      relevant prostate cancer and response to ADT. 

PMID- 24090975
TI  - Developmental cis-regulatory analysis of the cyclin D gene in the sea urchin
      Strongylocentrotus purpuratus.
AB  - Cyclin D genes regulate the cell cycle, growth and differentiation in response to
      intercellular signaling. While the promoters of vertebrate cyclin D genes have
      been analyzed, the cis-regulatory sequences across an entire cyclin D locus have
      not. Doing so would increase understanding of how cyclin D genes respond to the
      regulatory states established by developmental gene regulatory networks, linking
      cell cycle and growth control to the ontogenetic program. Therefore, we conducted
      a cis-regulatory analysis on the cyclin D gene, SpcycD, of the sea urchin,
      Strongylocentrotus purpuratus, during embryogenesis, identifying upstream and
      intronic sequences, located within six defined regions bearing one or more cis
      regulatory modules each. 

PMID- 24090976
TI  - Marginal zone lymphomas and infectious agents.
AB  - A link with infectious agents, bacteria and viruses in particular, has been
      reported for many lymphoma entities. Marginal zone lymphomas (extranodal, nodal
      and splenic forms) are frequently associated with chronic infections, with
      important clinical, molecular, biological, and therapeutic implications. The well
      known correlation between Helicobacter pylori and gastric MALT-lymphoma, the
      recently reported links between Chlamydophila psittaci and ocular adnexal MALT
      lymphoma and Borrelia burgdorferi and cutaneous MALT lymphoma constitute the best
      studied examples of lymphomagenic activity of bacteria, while the hepatitis C
      virus represents the most extensively investigated virus associated with marginal
      zone lymphomas. Biological and clinical features, therapeutic implications and
      future perspectives of these lymphoma-microbial associations are discussed in
      this review. 

PMID- 24090977
TI  - Antigen-specific immunomodulation for type 1 diabetes by novel recombinant
      antibodies directed against diabetes-associates auto-reactive T cell epitope.
AB  - The trimolecular complex composed of autoreactive T-cell receptor, MHC class II,
      and an autoantigenic peptide plays a central role in the activation of pathogenic
      Islet-specific CD4+ T cells in type 1 diabetes (T1D). We isolated and
      characterized novel antibodies against autoreactive T-cell epitopes associated
      with T1D. Our antibodies mimic the specificity of the T-cell receptor (TCR),
      while binding MHC class II/peptide complexes in an autoantigen peptide specific,
      MHC-restricted manner. The isolated TCR-like antibodies were directed against the
      minimal T-cell epitope GAD-555-567 in the context of the HLA-DR4-diabetic
      associated molecule. A representative high-affinity TCR-like antibody clone
      (G3H8) enabled the detection of intra- and extra-cellular DR4/GAD-555-567
      complexes in antigen presenting cells. I561M single mutation at the central
      position (P5) of the GAD-555-567 peptide abolished the binding of G3H8 to the
      DR4/GAD complex, demonstrating its high fine TCR-like specificity. The G3H8 TCR
      like antibody significantly inhibited GAD-555-567 specific, DR4 restricted T-cell
      response in vitro and in vivo in HLA-DR4 transgenic mice. Our findings constitute
      a proof-of-concept for the utility of TCR-like antibodies as antigen-specific
      immunomodulation agents for regulating pathogenic T-cells and suggest that TCR
      like antibodies targeting autoreactive MHC class II epitopes are valuable
      research tools that enable studies related to antigen presentation as well as
      novel therapeutic agents that may be used to modulate autoimmune disorders such
      as T1D.

PMID- 24090978
TI  - Increased-offset reverse shoulder arthroplasty for the treatment of failed post
      traumatic humeral head replacement.
AB  - BACKGROUND: Late complications after humeral head replacement (HHR) for
      comminuted proximal humeral fractures are common and may necessitate revision
      surgery. This study evaluated the outcome of revision surgery of failed post
      traumatic HHR with a less medialized reverse shoulder prosthesis. METHODS: Thirty
      three patients with failed post-traumatic HHR due to rotator-cuff insufficiency
      and glenoid erosion, but with sufficient preservation of the glenoid bone stock
      to permit primary stability of an inverted glenoid implant, underwent revision
      using the Bayley-Walker reverse shoulder prosthesis (Stanmore Implants, Elstree,
      UK) and were monitored up for a mean of 31 months. Outcome measures included the
      Oxford Shoulder Score, subjective shoulder value, pain rating, active range of
      motion, and shoulder radiographs. RESULTS: The average postrevision Oxford
      Shoulder Score and subjective shoulder value improved from 50 +/- 6 to 29 +/- 11
      and from 23 +/- 19 to 51 +/- 23, respectively (P < .001). Pain level decreased
      from 6.2 +/- 2.1 to 1.4 +/- 2.0 (P < .001). Active forward flexion increased from
      34 degrees  +/- 22 degrees  to 63 degrees  +/- 30 degrees  and external rotation
      from 11 degrees  +/- 14 degrees  to 20 degrees  +/- 16 degrees (P < .01). More
      patients were able to use their affected arm to reach a functional triangle
      consisting the mouth, opposite armpit, and ipsilateral buttock after revision
      (24% vs 73%; P < .001). Seven patients (21%) had postrevision complications. No
      glenoid loosening or scapular notching occurred. CONCLUSION: Revision of failed
      post-traumatic HHR with the Bayley-Walker shoulder offers reliable pain relief
      and improvement in shoulder function with a complication rate similar to other
      reverse prostheses. Nevertheless, revision shoulder arthroplasty remains
      challenging with a high rate of complications.

PMID- 24090979
TI  - Frozen shoulder and the Big Five personality traits.
AB  - BACKGROUND: In the past, several studies have suggested the existence of a
      "periarthritic personality" in patients with frozen shoulder. We conducted a
      study to determine differences in personality traits in patients with primary and
      secondary frozen shoulders. MATERIALS AND METHODS: We prospectively evaluated 118
      patients (84 women and 34 men; mean age, 53.8 years; SD 7.56) with a frozen
      shoulder. Of these patients, 48 had an idiopathic frozen shoulder and 70 had a
      secondary frozen shoulder. Personality traits were determined by the NEO Five
      Factor Inventory (NEO-FFI) scale. This questionnaire measures the 5 major
      personality traits and is based on the norms determined in a neutral test
      situation for 2415 controls. RESULTS: Compared with healthy controls, no
      differences in personality traits were found in patients with primary and
      secondary frozen shoulder, except for Conscientiousness and Extraversion, for
      which patients with secondary frozen shoulder scored significantly higher than
      healthy controls. Patients with primary frozen shoulder scored significantly
      higher on Openness to Experience than did patients with secondary frozen
      shoulder; on the other 4 Big Five personality traits, no significant differences
      were found between patients with primary and secondary frozen shoulder. More
      specifically, patients with idiopathic frozen shoulder did not score higher on
      the trait Neuroticism as would be expected from previous publications.
      CONCLUSIONS: Our study results do not indicate that patients with an idiopathic
      frozen shoulder have a specific personality compared with healthy controls. Only
      a few differences were found in personality traits when the entire frozen
      shoulder group was compared with healthy controls and between patients with
      primary and secondary frozen shoulders. The results of this study suggest that
      these differences are not sufficient to speak about a specific "frozen shoulder
      personality."

PMID- 24090980
TI  - Role of the superior labrum after biceps tenodesis in glenohumeral stability.
AB  - BACKGROUND: Little is known about the role that a torn superior labrum (SLAP)
      plays in glenohumeral stability after biceps tenodesis. This biomechanical study
      evaluated the contribution of a type II SLAP lesion to glenohumeral translation
      in the presence of biceps tenodesis. The authors hypothesize that subsequent to
      biceps tenodesis, a torn superior labrum does not affect glenohumeral stability
      and therefore does not require anatomic repair in an overhead throwing athlete.
      METHODS: Baseline anterior, posterior, and abduction and maximal external
      rotation glenohumeral translation data were collected from 20 cadaveric
      shoulders. Translation testing was repeated after the creation of anterior (n =
      10) and posterior (n = 10) type II SLAP lesions. Translation re-evaluation after
      biceps tenodesis was performed for each specimen. Finally, anatomic SLAP lesion
      repair and testing were performed. RESULTS: Anterior and posterior SLAP lesions
      led to significant increases in glenohumeral translation in all directions (P <
      .0125). Biceps tenodesis showed no significance in stability compared with SLAP
      alone (P > .0125). Arthroscopic repair of anterior SLAP lesions did not restore
      anterior translation compared with the baseline state (P = .0011) but did restore
      posterior (P = .823) and abduction and maximal external rotation (P = .806)
      translations. Repair of posterior SLAP lesions demonstrated no statistical
      difference compared with the baseline state (P > .0125). CONCLUSIONS: With no
      detrimental effect on glenohumeral stability in the presence of a SLAP lesion,
      biceps tenodesis may be considered a valid primary or revision surgery for
      patients suffering from symptomatic type II SLAP tears. However, biceps tenodesis
      should be considered with caution as the primary treatment of SLAP lesions in
      overhead throwing athletes secondary to its inability to completely restore
      translational stability.

PMID- 24090981
TI  - Immobilization in internal or external rotation does not change recurrence rates
      after traumatic anterior shoulder dislocation.
AB  - BACKGROUND: The objective of this study was to systematically review and
      quantitatively synthesize the data on recurrence rates after shoulder
      immobilization in internal versus external rotation in first-time, traumatic
      shoulder dislocations. MATERIALS AND METHODS: We performed a systematic search of
      the keywords "(((external rotation) OR internal rotation) AND immobilization) AND
      shoulder" in the online databases PubMed, EMBASE, CINAHL (Cumulative Index to
      Nursing and Allied Health Literature), and the Cochrane Library. Random-effects
      models were used to calculate the cumulatively pooled risk ratios (RRs) of
      recurrent shoulder dislocations. All analyses were also stratified by age.
      RESULTS: We included 5 studies with a total of 471 patients (230 internal
      rotation and 241 external rotation) published between 2001 and 2011 in English.
      The pooled random-effects RR for recurrence of shoulder dislocations at all ages
      was 0.74 (95% confidence interval [CI], 0.44-1.27; P = .278). The RR was 0.70
      (95% CI, 0.38 to 1.29; P = .250) for patients aged 30 years or younger and 0.78
      (95% CI, 0.32 to 1.88; P = .579) for those aged older than 30 years. CONCLUSION:
      The current best evidence does not support a relative effectiveness of
      immobilization in external rotation compared with internal rotation to avoid
      recurrent shoulder dislocations in patients with traumatic anterior shoulder
      dislocations.

PMID- 24090982
TI  - Biomechanical testing of small versus large lesser tuberosity osteotomies: effect
      on gap formation and ultimate failure load.
AB  - BACKGROUND: Subscapularis muscle dysfunction after total shoulder arthroplasty
      (TSA) can be a devastating complication. Recent biomechanical and clinical
      results suggest the superiority of lesser tuberosity osteotomy (LTO) over
      subscapularis tenotomy; however, disagreement over the best repair technique
      remains. This study aimed to characterize the strength of 2 novel repair
      techniques for LTO fixation compared with standard tenotomy and dual-row
      tuberosity osteotomies during TSA. METHODS: Twenty fresh frozen cadaveric
      shoulders were dissected of all soft tissues except the humeri and attached
      subscapularis myotendinous unit. Humeri and subscapularis muscle belly were
      secured to a materials testing frame and subjected to cyclic loading, followed by
      load to failure for characterization of gap formation, ultimate failure load, and
      mechanism of failure. Repair techniques investigated were traditional
      subscapularis tenotomy and dual-row fleck LTO compared with novel techniques of
      single-cable and 2-suture large LTO repairs. RESULTS: No significant difference
      in ultimate failure load was noted among the repair techniques (P = .565). The
      tenotomy repair (6.0 +/- 3.9 mm) displayed significantly greater gapping in
      response to increasing load than LTO repair techniques (P < .05). No significant
      difference was noted between any LTO repairs at specific loads during cyclic
      testing (P > .05). CONCLUSION: Our study displayed superior repair integrity of
      LTO vs tenotomy repairs. The advantages of the 2-suture large LTO technique over
      other LTO techniques include its simple technique, with a minimum amount of
      suture, avoidance of metallic hardware, and greater access to the glenoid, while
      providing comparable repair stability. Further research is warranted to fully
      evaluate these new techniques.

PMID- 24090983
TI  - Neuropathy of the suprascapular nerve and massive rotator cuff tears: a
      prospective electromyographic study.
AB  - BACKGROUND: An association between massive rotator cuff tear (RCT) and
      suprascapular nerve neuropathy has previously been suggested. The anatomic course
      of the suprascapular nerve is relatively fixed along its passage. Thus, injury to
      the nerve by trauma, compression, and iatrogenic reasons is well documented.
      However, the association between retraction of the RCT and development of
      neuropathy of the suprascapular nerve remains unclear. We aimed to prospectively
      evaluate the suprascapular nerve for preoperative neurodiagnostic abnormalities
      in shoulders with massive RCT. METHODS AND MATERIALS: A prospective study was
      performed in 2 centers. Fifty patients with retracted tears of both supraspinatus
      and infraspinatus were evaluated. This was confirmed with preoperative computed
      tomography arthrography, and the fatty infiltration of the affected muscles was
      graded. Forty-nine preoperative electromyograms were performed in a standardized
      fashion and the results analyzed twice. RESULTS: Of 49 shoulders, 6 (12%) had
      neurologic lesions noted on electromyography: 1 suprascapular nerve neuropathy, 1
      radicular lesion of the C5 root, 1 affected electromyogram in the context of a
      previous stroke, and 3 cases of partial axillary nerve palsy with a history of
      shoulder dislocation. No difference or diminution of the latency or amplitude of
      the electromyographic curve was found in the cases that presented significant
      fatty infiltration. CONCLUSION: This study did not detect a suprascapular lesion
      in the majority of cases of massive RCT. With a low association of neuropathy
      with massive RCT, we find no evidence to support the routine practice of
      suprascapular nerve release when RCT repair is performed.

PMID- 24090984
TI  - Reverse total shoulder arthroplasty in patients of varying body mass index.
AB  - BACKGROUND: Body mass index (BMI) is an independent predictor of complications
      after hip and knee arthroplasty. Whether similar trends apply to patients
      undergoing reverse total shoulder arthroplasty (RTSA) is unknown. METHODS: A
      retrospective review of primary RTSAs with a minimum 90-day follow-up were
      included. Complications were classified as major or minor and medical or
      surgical. Patients were classified into 3 groups: normal BMI (BMI <25 kg/m(2)),
      overweight or mildly obese (BMI 25-35 kg/m(2)), and moderately or severely obese
      (BMI >35 kg/m(2)). RESULTS: Of the 119 patients met our inclusion criteria, 30
      (25%) had a BMI of less than 25 kg/m(2); 65 (55%) had a BMI of 25 to 35 kg/m(2),
      and 24 (20%) had BMI exceeding 35 kg/m(2). Complications occurred in 30 patients
      (25%), comprising major in 11 (9%), minor in 19 (16%), surgical in 21 (18%), and
      medical in 14 (12%). The most common surgical complications were acute blood loss
      anemia requiring transfusion (8.4%) and dislocation (4.2%). The most common
      medical complications were atelectasis (2.5%) and acute renal insufficiency
      (2.5%). Patients with a BMI exceeding 35 kg/m(2) had a significantly higher
      overall complication rate (P < .05) and intraoperative blood loss (P = .05) than
      the other groups. Patients with BMI of less than 25 kg/m(2) had a greater overall
      complication rate than those with a BMI of 25 to 35 kg/m(2) (P < .05).
      Multivariate regression analysis demonstrated BMI was the only significant
      determinant of overall complication rates and medical complication rates (P <
      .05). CONCLUSION: Patients with a BMI exceeding 35 kg/m(2) (severely obese) or a
      BMI of less than 25 kg/m(2) have higher rates of complication after RTSA.

PMID- 24090985
TI  - Woven silk fabric-reinforced silk nanofibrous scaffolds for regenerating load
      bearing soft tissues.
AB  - Although three-dimensional (3-D) porous regenerated silk scaffolds with
      outstanding biocompatibility, biodegradability and low inflammatory reactions
      have promising application in different tissue regeneration, the mechanical
      properties of regenerated scaffolds, especially suture retention strength, must
      be further improved to satisfy the requirements of clinical applications. This
      study presents woven silk fabric-reinforced silk nanofibrous scaffolds aimed at
      dermal tissue engineering. To improve the mechanical properties, silk scaffolds
      prepared by lyophilization were reinforced with degummed woven silk fabrics. The
      ultimate tensile strength, elongation at break and suture retention strength of
      the scaffolds were significantly improved, providing suitable mechanical
      properties strong enough for clinical applications. The stiffness and degradation
      behaviors were then further regulated by different after-treatment processes,
      making the scaffolds more suitable for dermal tissue regeneration. The in vitro
      cell culture results indicated that these scaffolds maintained their excellent
      biocompatibility after being reinforced with woven silk fabrics. Without
      sacrifice of porous structure and biocompatibility, the fabric-reinforced
      scaffolds with better mechanical properties could facilitate future clinical
      applications of silk as matrices in skin repair. 

PMID- 24090986
TI  - Long-time aging in 3 mol.% yttria-stabilized tetragonal zirconia polycrystals at
      human body temperature.
AB  - We present new findings on the low-temperature degradation of yttria-stabilized
      zirconia at 37 degrees C over several years and at high and low partial pressures
      of water. With the aid of focused ion beam cross-section confirmation studies we
      are able to show an extensive linear, continuous degradation without retardation,
      even at low temperatures and low water pressures. The characteristic layer growth
      and its inferred rate constant imply a lifetime of tens of years under simple
      tension and open the possibility of studying the longevity of these ceramics more
      rigorously. In addition, we show reproducibility complications of accelerated
      aging tests by the use of different autoclaves and possible implications for
      standardized procedures. 

PMID- 24090987
TI  - Low density biodegradable shape memory polyurethane foams for embolic biomedical
      applications.
AB  - Low density shape memory polymer foams hold significant interest in the
      biomaterials community for their potential use in minimally invasive embolic
      biomedical applications. The unique shape memory behavior of these foams allows
      them to be compressed to a miniaturized form, which can be delivered to an
      anatomical site via a transcatheter process and thereafter actuated to embolize
      the desired area. Previous work in this field has described the use of a highly
      covalently crosslinked polymer structure for maintaining excellent mechanical and
      shape memory properties at the application-specific ultralow densities. This work
      is aimed at further expanding the utility of these biomaterials, as implantable
      low density shape memory polymer foams, by introducing controlled
      biodegradability. A highly covalently crosslinked network structure was
      maintained by use of low molecular weight, symmetrical and polyfunctional
      hydroxyl monomers such as polycaprolactone triol (PCL-t, Mn= 900 g), N,N,N0,N0
      tetrakis(hydroxypropyl)ethylenediamine and tris(2-hydroxyethyl)amine. Control
      over the degradation rate of the materials was achieved by changing the
      concentration of the degradable PCL-t monomer and by varying the material
      hydrophobicity. These porous SMP materials exhibit a uniform cell morphology and
      excellent shape recovery, along with controllable actuation temperature and
      degradation rate. We believe that they form a new class of low density
      biodegradable SMP scaffolds that can potentially be used as "smart" non-permanent
      implants in multiple minimally invasive biomedical applications.

PMID- 24090988
TI  - A chlorhexidine-loaded biodegradable cellulosic device for periodontal pockets
      treatment.
AB  - Absorbent points widely used in endodontic therapy were transformed into
      bioresorbable chlorhexidine delivery systems for the treatment of the periodontal
      pocket by preventing its recolonization by the subgingival microflora. These
      paper points (PPs) were first oxidized to promote their resorption, then grafted
      with beta-cyclodextrin (CD) or maltodextrin (MD) in order to achieve sustained
      delivery of chlorhexidine. We investigated the oxidation step parameters through
      the time of reaction and the nitric and phosphoric acid ratios in the oxidizing
      mixture, and then the dextrin grafting step parameters through the time and
      temperature of reaction. A first selection of the appropriate functionalization
      parameters was undertaken in relation to the degradation profile kinetics of the
      oxidized (PPO) and oxidized-grafted samples (PPO-CD and PPO-MD). Samples were
      then loaded with chlorhexidine digluconate (digCHX), a widely used antiseptic
      agent in periodontal therapy. The release kinetics of digCHX from PPO-CD and PPO
      MD samples were compared to PP, PPO and to PerioChip((r)) (a commercial digCHX
      containing gelatine chip) in phosphate buffered saline (pH 7.4) by ultraviolet
      spectrophotometry. The cytocompatibility of the oxidized-grafted PP was
      demonstrated by cell proliferation assays. Finally, the disc diffusion test from
      digCHX loaded PPO-MD samples immersed in human plasma was developed on pre
      inoculated agar plates with four common periodontal pathogenic strains:
      Fusobacterium nucleatum, Prevotella melaninogenica, Aggregatibacter actinomycetem
      comitans and Porphyromonas gingivalis. To conclude, the optimized oxidized
      dextrin-grafted PPs responded to our initial specifications in terms of
      resorption and digCHX release rates and therefore could be adopted as a reliable
      complementary periodontal therapy.

PMID- 24090990
TI  - Controlled assembly: a prerequisite for the use of recombinant spider silk in
      regenerative medicine?
AB  - Recent biotechnological progress has enabled the production of spider silk
      proteins, spidroins, in heterologous hosts. Matrices based on recombinant
      spidroins support stem cell growth and are well tolerated when implanted in
      living tissue, thus the material is highly attractive for use in regenerative
      medicine. However, the matrices made are far from natural silk in terms of
      mechanical properties and are either spontaneously assembled, which results in
      heterogeneous products, or spun from harsh solvents with the concomitant risk of
      harmful remnants in the final products. If we could mimic the spider's aqueous
      silk spinning process we would likely obtain a material that had reproducible and
      better characteristics and that more easily could be transferred to clinical
      practice. Herein, the knowledge of the spiders' silk production system and the
      prerequisites for artificial spinning and assembly of recombinant proteins are
      reviewed and discussed in a biomedical context. 

PMID- 24090989
TI  - Chronic inflammation in biomaterial-induced periprosthetic osteolysis: NF-kappaB
      as a therapeutic target.
AB  - Biomaterial-induced tissue responses in patients with total joint replacement are
      associated with the generation of wear particles, which may lead to chronic
      inflammation and local bone destruction (periprosthetic osteolysis). Inflammatory
      reactions associated with wear particles are mediated by several important
      signaling pathways, the most important of which involves the transcription factor
      NF-kappaB. NF-kappaB activation is essential for macrophage recruitment and
      maturation, as well as the production of pro-inflammatory cytokines and
      chemokines such as TNF-alpha, IL-1beta, IL-6 and MCP1. In addition, NF-kappaB
      activation contributes to osteoclast differentiation and maturation via
      RANK/RANKL signaling, which increases bone destruction and reduces bone
      formation. Targeting individual downstream cytokines directly (such as TNF-alpha
      or IL-1beta) may not effectively prevent wear particle induced osteolysis. A more
      logical upstream therapeutic approach may be provided by direct modulation of the
      core IkappaB/IKKalpha/beta/NF-kappaB signaling pathway in the local environment.
      However, the timing, dose and strategy for administration should be considered.
      Suppression of chronic inflammation via inhibition of NF-kappaB activity in
      patients with malfunctioning joint replacements may be an effective strategy to
      mitigate wear particle induced periprosthetic osteolysis. 

PMID- 24090991
TI  - Marijuana for pain relief: don't jump to conclusions.

PMID- 24090992
TI  - Response to Stacey and Moller's letter to the editor.

PMID- 24090993
TI  - Deep massage to posterior calf muscles in combination with neural mobilization
      exercises as a treatment for heel pain: a pilot randomized clinical trial.
AB  - BACKGROUND: Plantar heel pain syndrome (PHPS) is a common foot disorder; however,
      there is limited clinical evidence on which to base treatment. Repeated clinical
      observations indicating heel pain during heel rise and minisquat on the affected
      leg, involving activation of posterior calf muscles, formed the basis of this
      study. OBJECTIVE: To compare deep massage therapy to posterior calf muscles and
      neural mobilization with a self-stretch exercise program (DMS) to a common
      treatment protocol of ultrasound therapy to the painful heel area with the same
      self-stretch exercises (USS). METHODS: Patients with PHPS were assigned to a
      program of 8 treatments over a period of 4-6 weeks in a single-blind randomized
      clinical trial. Functional status (FS) at admission and discharge from therapy as
      measured by the Foot & Ankle Computerized Adaptive Test was the main outcome
      measure. RESULTS: Sixty-nine patients were included in the trial (mean age 53,
      standard deviation (SD) 13, range 25-86, 57% women), 36 received DMS treatment
      and 33 with USS. The overall group-by-time interaction for the mixed-model
      analysis of variance (ANOVA) was found statistically significant (p=0.034), with
      a change of (mean (confidence interval, CI)) 15 (9-21) and 6 (1-11) FS points for
      the DMS and USS groups, respectively. CONCLUSIONS: Data indicated that both
      treatment protocols resulted in an overall short-term improvement, however, DMS
      treatment was significantly more effective in treating PHPS than USS treatment.

PMID- 24090994
TI  - Modulation of COX, LOX and NFkappaB activities by Xanthium spinosum L. root
      extract and ziniolide.
AB  - Xanthium spinosum L. (Asteraceae) is a medicinal weed distributed worldwide. Many
      of its diverse ethnopharmacological uses - namely diarrhoea, inflammation, liver
      disorders, snake bite and fever - are linked - at least in part - to an
      uncontrolled release of arachidonic acid metabolites. The crude extract of X.
      spinosum roots from Jordanian origin dose-dependently inhibited the 5-LOX (IC50
      is approximately equal to 10 MUg/mL), COX-1(IC50 is approximately equal to 50
      MUg/mL), and 12-LOX (IC50 is approximately equal to 170 MUg/mL) enzymatic
      pathways in intact pro-inflammatory cells. A direct activity at the level of PLA2
      is not probable, but the extract induced the synthesis of the anti-inflammatory
      eicosanoid 15(S)-HETE, which may in turn inhibit this enzyme. 5-LOX bioguided
      fractionation of the crude extract led to the isolation of ziniolide, a known
      12,8-guaianolide sesquiterpene lactone, from the hydro-alcoholic fraction of the
      n-hexane extract (IC50=69 MUM). Both the plant extract and ziniolide are in vitro
      inhibitors of the phorbol-induced NFkappaB activation, a key regulator of the
      arachidonic pathway.

PMID- 24090995
TI  - Resveratrol suppresses cell proliferation via inhibition of STAT3 phosphorylation
      and Mcl-1 and cIAP-2 expression in HTLV-1-infected T cells.
AB  - Adult T-cell leukemia (ATL) is an aggressive malignancy of peripheral T cells
      infected with human T-cell leukemia virus type 1 (HTLV-1). The prognosis of
      patients with aggressive ATL remains poor because ATL cells acquire resistance to
      conventional cytotoxic agents. Therefore, development of novel agents is urgently
      needed. We examined the effects of resveratrol, a well-known polyphenolic
      compound, on cell proliferation and survival of HTLV-1-infected T-cell lines, MT
      2 and HUT-102. We found that resveratrol suppressed cell proliferation and
      induced cell death of MT-2 and HUT-102 cells. Immunoblot analysis showed
      inhibition of myeloid cell leukemia sequence (Mcl)-1 and cellular inhibitor of
      apoptosis protein (cIAP)-2 expression as well as signal transducers and
      activators of transcription (STAT) 3 phosphorylation at Tyr(705) and Ser(727) in
      resveratrol-treated cells. We also observed cleavage of caspase-3 and poly(ADP
      ribose) polymerase in resveratrol-treated cells, indicating that resveratrol
      induces caspase-dependent apoptosis in MT-2 and HUT-102 cells. In addition, the
      STAT3 inhibitor S3I-201 not only induced cell growth arrest and cell death but
      also activated caspase-3 in MT-2 and HUT-102 cells, indicating that STAT3 may be
      a therapeutic target for ATL. These results suggest that resveratrol presents a
      potent anti-proliferative effect in part via the suppression of STAT3
      phosphorylation and Mcl-1 and cIAP-2 expression in HTLV-1-infected T cells.
      Resveratrol merits further investigation as a potential chemotherapeutic agent
      for ATL. 

PMID- 24090996
TI  - Distinct sensitivity of CD8+ CD4- and CD8+ CD4+ leukemic cell subpopulations to
      cyclophosphamide and rapamycin in Notch1-induced T-ALL mouse model.
AB  - The Notch1 signaling pathway plays an essential role in cell growth and
      differentiation. Over-expression of the intracellular Notch1 domain (ICN1) in
      murine hematopoietic cells is able to induce robust T-cell acute lymphoblastic
      leukemia (T-ALL) in mice. Here we explored the drug sensitivity of T-ALL cells in
      two subpopulations of CD8(+)CD4(+) and CD8(+)CD4(-) cells in Notch1-induced T-ALL
      mice. We found that Notch1 induced T-ALL cells could be decreased by
      chemotherapeutic drug cyclophosphamide (CTX). CD8(+)CD4(-) T-ALL cells were more
      sensitive to CTX treatment than CD8(+)CD4(+) T-ALL cells. The percentage of
      apoptotic cells induced by CTX treatment was higher in CD8(+)CD4(-) T-ALL cells.
      T-ALL cells were also inhibited by inhibitor of mTORC1 rapamycin. CD8(+)CD4(+) T
      ALL cells were more susceptible to rapamycin treatment than CD8(+)CD4(-) T-ALL
      cells. Rapamycin treatment selectively arrested more CD8(+)CD4(+) T-ALL cells at
      G0 phase of cell cycle. A combination of the two drugs significantly improved
      overall survival of T-ALL bearing mice when compared with CTX or rapamycin alone.
      These results indicated that CD8(+)CD4(+) and CD8(+)CD4(-) leukemia cell
      populations had distinct drug sensitivity. 

PMID- 24090997
TI  - The fusion partner specifies the oncogenic potential of NUP98 fusion proteins.
AB  - NUP98 is among the most promiscuously translocated genes in hematological
      diseases. Among the 28 known fusion partners, there are two categories: homeobox
      genes and non-homeobox genes. The homeobox fusion partners are well-studied in
      animal models, resulting in HoxA cluster overexpression and hematological
      disease. The non-homeobox fusion partners are less well studied. We created
      transgenic animal models for three NUP98 fusion genes (one homeobox, two non
      homeobox), and show that in this system, the NUP98-homeobox fusion promotes self
      renewal and aberrant gene expression to a significantly greater extent. We
      conclude that homeobox partners create more potent NUP98 fusion oncogenes than do
      non-homeobox partners. 

PMID- 24090998
TI  - Separate attentional components modulate early visual cortex excitability.

PMID- 24090999
TI  - Psychosocioprofessional and familial becoming of formers Buruli ulcer patients in
      Benin.
AB  - Buruli ulcer (BU), an emerging disease caused by Mycobacterium ulcerans, causes
      severe impairments. In literature, no survey has been devoted to the cured
      patients returned back home. OBJECTIVE: To analyze the long-term psychosocial,
      professional and family repercussions of BU on former patients. METHOD: Cross
      sectional descriptive and analytic study on 244 formers patients seen at the
      Screening and Treatment BU Center of Allada from 2005 to 2009 and followed at
      home from January to July 2010. RESULTS: On the psychosocial level, 50.8% cured
      patients attributed the disease to witchcraft (mostly adults and teenagers); 90.
      2% did not feel guilty (mostly children), 48.9% of the adults felt diminished,
      31.7% are depressed and 19.5% anxious. On professional level, 81.0% of workers
      had gotten back to work, in the same job for 75.0% of them while 25.0% had
      changed jobs; 90.1% of children went back school, 29.4% followed a normal
      schooling but 70% did experience academic delay. On family level, 2.5% of
      patients were rejected by their families. CONCLUSION: After returning home,
      former UB patients suffered of severe psychosocioprofessional and familial
      repercussions that suggested an organization of their home monitoring.

PMID- 24091000
TI  - Frequency of occurrence and antimicrobial susceptibility of Gram-negative
      bacteremia isolates in patients with urinary tract infection: results from United
      States and European hospitals (2009-2011).
AB  - We evaluated the frequency of occurrence and antimicrobial susceptibility
      patterns of Gram-negative bacteria isolated from bacteremic patients with UTI
      from European (EU) and United States (USA) hospitals during a 3-year period (2009
      2011). Susceptibility testing was performed by the reference broth microdilution
      method on 2071 Gram-negative bacilli. The most frequently isolated pathogens were
      Escherichia coli (63.3/71.3% in USA/EU), Klebsiella spp. (16.7/11.2%) and Proteus
      mirabilis (6.4/5.0%). Escherichia coli susceptibility rates were generally
      similar in the USA and EU, with extended-spectrum beta-lactamase (ESBL)-phenotype
      rates at 8.1% in both regions. Among Klebsiella spp., ESBL rates varied from
      11.4/17.1% in 2009 to 16.1/40.4% in 2011 in USA/EU, and susceptibility rates were
      generally lower in EU compared to the USA. Pseudomonas aeruginosa exhibited lower
      susceptibility rates to ceftazidime, meropenem and piperacillin/tazobactam in EU
      (78.4, 78.4 and 76.5%, respectively) compared to USA (91.2, 88.2 and 91.2%,
      respectively). In summary, very few antimicrobials provided satisfactory coverage
      (>90%) when tested against Klebsiella spp. and P. aeruginosa isolates in EU. 

PMID- 24091001
TI  - Health anxiety disorders in older adults: conceptualizing complex conditions in
      late life.
AB  - Health anxiety disorders (e.g., hypochondriasis) are prevalent but understudied
      in older adults. Existing research suggests that severe health anxiety has a late
      age of onset, perhaps because of comorbidity with physical health conditions that
      are more likely to occur with aging. Despite being under diagnosed in later life
      due to a lack of age-appropriate diagnostic criteria, significant positive
      associations with age suggest that health anxiety disorders are more prevalent in
      older than younger adults. Preliminary research also highlights the complexity of
      these disorders in older adults and the potential importance of medical morbidity
      as a risk factor. This review explores the complexities of health anxiety
      disorders in later life with a focus on understanding defining features,
      prevalence rates, correlates, assessment, diagnosis, and treatment. We offer a
      theoretical model of the development of severe health anxiety among older adults
      to encourage further research on this important and under-studied topic. 

PMID- 24091002
TI  - High prevalence of enteroparasitosis in urban slums of Belo Horizonte-Brazil.
      Presence of enteroparasites as a risk factor in the family group.
AB  - The present study evaluates the prevalence of enteroparasitosis in the urban
      slums of Belo Horizonte, Brazil and the risk of transmitting enteroparasites to
      the family members of infected individuals. Stool samples were collected and
      examined at clinical laboratories near each slum. Individuals were identified and
      classified as positive for parasitosis (IP(+)), and individuals with negative
      stool tests were classified as negative for parasitosis (IP(-)) and enrolled as
      control patients. We collected samples from 594 patients, of which 20.2% and
      79.8% were classified as IP(+) and IP(-), respectively. In addition, 744 family
      members (FIPs) effectively participated in the study by providing fecal samples.
      In total, 1338 participants were evaluated. Of these, 34.6% were tested positive
      for parasitosis. Blastocystis was the most prevalent parasite, infecting 22.4% of
      individuals. Among FIPs, the overall prevalence was 46.1%. Of these, 50.6% and
      44.7% were classified as FIPs(+) and FIPs(-), respectively. These results showed
      that IP(+) did not impact the prevalence of infection within the studied
      communities, not constituting index cases of specific risk behaviors, suggesting
      that, in fact, these communities are exposed to similar oral-fecal routes of
      contamination. 

PMID- 24091003
TI  - A novel approach for planning orthognathic surgery: the integration of dental
      casts into three-dimensional printed mandibular models.
AB  - A method of producing a composite model consisting of a three-dimensional printed
      mandible bearing plaster teeth is presented. Printed models were obtained from
      cone beam computed tomograms (CBCT) of dry human mandibles. The plaster casts of
      the teeth were obtained from impressions of the teeth of the dry mandibles. The
      distorted teeth of the printed models were removed and replaced by the plaster
      casts of the teeth using a simple transfer jig. The accuracy of the composite
      models obtained from six mandibles was assessed from laser scans. The scans of
      the dry mandibles and the composite models were superimposed and the magnitude of
      the discrepancies at six points on the dentition and six on the mandible were
      obtained. It was concluded that the errors of the method were small enough to be
      clinically significant. The use of the composite models is illustrated in two
      clinical cases. 

PMID- 24091004
TI  - Autoimmune animal models in the analysis of the CD47-SIRPalpha signaling pathway.
AB  - Signal regulatory protein alpha (SIRPalpha), also known as SHPS-1/SIRPA, is an
      immunoglobulin superfamily protein that binds to the protein tyrosine
      phosphatases Shp1 and Shp2 through its cytoplasmic region and is predominantly
      expressed in dendritic cells and macrophages. CD47, a widely expressed
      transmembrane protein, is a ligand for SIRPalpha, with the two proteins
      constituting a cell-cell communication system. It was previously demonstrated
      that the CD47-SIRPalpha signaling pathway is important for prevention of
      clearance by splenic macrophages of red blood cells or platelets from the
      bloodstream. In addition, this signaling pathway is also implicated in
      homeostatic regulation of dendritic cells and development of autoimmunity. Here
      we describe the detailed protocols for methods that were used in our recent
      studies to study the role of the CD47-SIRPalpha signaling pathway in
      autoimmunity. We also demonstrate that hematopoietic SIRPalpha as well as
      nonhematopoietic CD47 are important for development of experimental autoimmune
      encephalomyelitis. Thus, we here strengthen the importance of experimental animal
      models as well as other methods for the study of molecular pathogenesis of
      autoimmunity. 

PMID- 24091005
TI  - Engineered antibodies for molecular imaging of cancer.
AB  - Antibody technology has transformed drug development, providing robust approaches
      to producing highly targeted and active therapeutics that can routinely be
      advanced through clinical evaluation and registration. In parallel, there is an
      emerging need to access similarly targeted agents for diagnostic purposes,
      including non-invasive imaging in preclinical models and patients. Antibody
      engineering enables modification of key properties (immunogenicity, valency,
      biological inertness, pharmacokinetics, clearance route, site-specific
      conjugation) in order to produce targeting agents optimized for molecular
      imaging. Expanded availability of positron-emitting radionuclides has led to a
      resurgence of interest and applications of immunoPET (immuno-positron emission
      tomography). Molecular imaging using engineered antibodies and fragments provides
      a general approach for assessing cell surface phenotype in vivo and stands to
      play an increasingly important role in cancer diagnosis, treatment selection, and
      monitoring of molecularly targeted therapeutics. 

PMID- 24091006
TI  - Your gut is right to turn left.
AB  - Transcriptional factor Pitx2 is a key regulator of left-right asymmetry in the
      developing gut. In this issue of Developmental Cell, Welsh et al. (2013) identify
      the formin Daam2, an effector of Wnt signaling, as a key cellular target of Pitx2
      required for morphogenetic events during asymmetric gut formation. 

PMID- 24091007
TI  - Forces in epithelial origami.
AB  - Recent efforts examining forces during morphogenesis suggest a role for
      mechanical crosstalk between epithelium and mesenchyme in tissue patterning.
      Reporting in Science, Shyer et al. (2013) show that differences between the
      mechanical properties of the developing intestinal epithelium and surrounding
      smooth muscle fold the epithelium into villi via mucosal buckling. 

PMID- 24091008
TI  - Polycomb group protein bodybuilding: working out the routines.
AB  - Polycomb group (PcG) proteins regulate gene expression by modifying chemical and
      structural properties of chromatin. Isono et al. (2013) now report in
      Developmental Cell a polymerization-dependent mechanism used by PcG proteins to
      form higher-order chromatin structures, referred to as Polycomb bodies, and
      demonstrate its necessity for gene silencing. 

PMID- 24091009
TI  - A histone timer for zygotic genome activation.
AB  - Histone H1 variants play key roles in the regulation of higher-order chromatin
      structure and have been implicated in numerous developmental processes. In this
      issue of Developmental Cell, Perez-Montero et al. (2013) present evidence that
      the Drosophila histone H1 variant dBigH1 prevents premature activation of the
      zygotic genome during early embryogenesis. 

PMID- 24091010
TI  - WRAMPing up calcium in migrating cells by localized ER transport.
AB  - Morphological plasticity and front-rear polarity are essential for directed cell
      migration. In this issue of Developmental Cell, Witze et al. (2013) demonstrate
      that Wnt5a-mediated signaling induces localization of the cortical endoplasmic
      reticulum to the trailing edge of melanoma cells and mediates calcium flux, rear
      detachment, and motility. 

PMID- 24091011
TI  - SAM domain polymerization links subnuclear clustering of PRC1 to gene silencing.
AB  - The Polycomb-group (PcG) repressive complex-1 (PRC1) forms microscopically
      visible clusters in nuclei; however, the impact of this cluster formation on
      transcriptional regulation and the underlying mechanisms that regulate this
      process remain obscure. Here, we report that the sterile alpha motif (SAM) domain
      of a PRC1 core component Phc2 plays an essential role for PRC1 clustering through
      head-to-tail macromolecular polymerization, which is associated with stable
      target binding of PRC1/PRC2 and robust gene silencing activity. We propose a role
      for SAM domain polymerization in this repression by two distinct mechanisms:
      first, through capturing and/or retaining PRC1 at the PcG targets, and second, by
      strengthening the interactions between PRC1 and PRC2 to stabilize transcriptional
      repression. Our findings reveal a regulatory mechanism mediated by SAM domain
      polymerization for PcG-mediated repression of developmental loci that enables a
      robust yet reversible gene repression program during development.

PMID- 24091012
TI  - Filopodia-like actin cables position nuclei in association with perinuclear actin
      in Drosophila nurse cells.
AB  - Controlling the position of the nucleus is vital for a number of cellular
      processes from yeast to humans. In Drosophila nurse cells, nuclear positioning is
      crucial during dumping, when nurse cells contract and expel their contents into
      the oocyte. We provide evidence that in nurse cells, continuous filopodia-like
      actin cables, growing from the plasma membrane and extending to the nucleus,
      achieve nuclear positioning. These actin cables move nuclei away from ring
      canals. When nurse cells contract, actin cables associate laterally with the
      nuclei, in some cases inducing nuclear turning so that actin cables become
      partially wound around the nuclei. Our data suggest that a perinuclear actin
      meshwork connects actin cables to nuclei via actin-crosslinking proteins such as
      the filamin Cheerio. We provide a revised model for how actin structures position
      nuclei in nurse cells, employing evolutionary conserved machinery.

PMID- 24091013
TI  - Interaction between meristem tissue layers controls phyllotaxis.
AB  - Phyllotaxis and vein formation are among the most conspicuous patterning
      processes in plants. The expression and polarization of the auxin efflux carrier
      PIN1 is the earliest marker for both processes, with mathematical models
      indicating that PIN1 can respond to auxin gradients and/or auxin flux. Here, we
      use cell-layer-specific PIN1 knockouts and partial complementation of auxin
      transport mutants to examine the interaction between phyllotactic patterning,
      which occurs primarily in the L1 surface layer of the meristem, and midvein
      specification in the inner tissues. We show that PIN1 expression in the L1 is
      sufficient for correct organ positioning, as long as the L1-specific influx
      carriers are present. Thus, differentiation of inner tissues can proceed without
      PIN1 or any of the known polar transporters. On theoretical grounds, we suggest
      that canalization of auxin flux between an auxin source and an auxin sink may
      involve facilitated diffusion rather than polar transport.

PMID- 24091016
TI  - SC-514, a selective inhibitor of IKKbeta attenuates RANKL-induced
      osteoclastogenesis and NF-kappaB activation.
AB  - The RANKL-induced NF-kappaB signaling pathway is essential for
      osteoclastogenesis. This study aims to identify specific inhibitors targeting NF
      kappaB signaling pathway, which might serve as useful small molecule inhibitors
      for the treatment and alleviation of osteoclast-mediated bone lytic diseases. By
      screening for compounds that selectively inhibit RANKL-induced NF-kappaB
      activation in RAW264.7 cells as monitored by luciferase reporter gene assay, we
      identified SC-514, a specific inhibitor of IKKbeta, as a candidate compound
      targeting osteoclastogenesis. SC-514 dose-dependently inhibits RANKL-induced
      osteoclastogenesis with an IC50 of <5MUM. At high concentrations, SC-514
      (>=12.5MUM) induced apoptosis and caspase 3 activation in RAW264.7 cells.
      Moreover, SC-514 specifically suppressed NF-kappaB activity owing to delayed
      RANKL-induced degradation of IkappaBalpha and inhibition of p65 nuclear
      translocation. Taken together, our results indicate that SC-514 impairs RANKL
      induced osteoclastogenesis and NF-kappaB activation. Thus, targeting IKKbeta by
      SC-514 presents as a potential treatment for osteoclast-related disorders such as
      osteoporosis and cancer-induced bone loss. 

PMID- 24091015
TI  - Wnt5a directs polarized calcium gradients by recruiting cortical endoplasmic
      reticulum to the cell trailing edge.
AB  - Wnt5a directs the assembly of the Wnt-receptor-actin-myosin-polarity (WRAMP)
      structure, which integrates cell-adhesion receptors with F-actin and myosin to
      form a microfilament array associated with multivesicular bodies (MVBs). The
      WRAMP structure is polarized to the cell posterior, where it directs tail-end
      membrane retraction, driving forward translocation of the cell body. Here we
      define constituents of the WRAMP proteome, including regulators of microfilament
      and microtubule dynamics, protein interactions, and enzymatic activity. IQGAP1, a
      scaffold for F-actin nucleation and crosslinking, is necessary for WRAMP
      structure formation, potentially bridging microfilaments and MVBs. Vesicle coat
      proteins, including coatomer-I subunits, localize to and are required for the
      WRAMP structure. Electron microscopy and live imaging demonstrate movement of the
      ER to the WRAMP structure and plasma membrane, followed by elevation of
      intracellular Ca2+. Thus, Wnt5a controls directional movement by recruiting
      cortical ER to mobilize a rear-directed, localized Ca2+ signal, activating
      actomyosin contraction and adhesion disassembly for membrane retraction.

PMID- 24091017
TI  - Targets in small cell lung cancer.
AB  - Recurrent small cell lung cancer is a recalcitrant malgnancy. The application of
      genomic technologies has begun to elucidate the large number of genetic
      abnormalities in SCLC. Several cell surface receptors are known to be
      overexpressed by SCLC in clinic specimens and cell in culture including GPCRs
      such as the bradykinin receptor, the chemokine receptor CXCR4, the vasopression
      receeptor and the three bomebsin receptors. The glucose transporter GLUT1, the
      tetraspanin family member PETA/CD151 and the immunoglobulin superfamily member
      ALCAM/CD166 are also overexpressed by SCLC. NCAM/CD56 is overexpressed by nearly
      all SCLC and is currently the target for an antibody drug conjugate in Phase II
      trial. Although SCLC is not considered a RTK driven disease, IGF1R and FGFRs are
      often overexpressed by SCLC. SCLC abberantly expresses several developmental
      transcription factors including ASCL1, SOX2, 4, and 11, OCT4, NANOG, PAX5;
      however, overexpression of MYC may be a driver in SCLC. Like other cancers, SCLC
      expresses survival factors and uses aerobic glycolysis as a major source of ATP.
      The drawback of many potential targets overexpressed by SCLC is expression of the
      same proteins by normal tissues. We are slowly learning more about the molecular
      abnormalities that occur in SCLC; however, therapeutic impact from new findings
      remains a goal to work toward.

PMID- 24091014
TI  - Integration of left-right Pitx2 transcription and Wnt signaling drives asymmetric
      gut morphogenesis via Daam2.
AB  - A critical aspect of gut morphogenesis is initiation of a leftward tilt, and
      failure to do so leads to gut malrotation and volvulus. The direction of tilt is
      specified by asymmetric cell behaviors within the dorsal mesentery (DM), which
      suspends the gut tube, and is downstream of Pitx2, the key transcription factor
      responsible for the transfer of left-right (L-R) information from early
      gastrulation to morphogenesis. Although Pitx2 is a master regulator of L-R organ
      development, its cellular targets that drive asymmetric morphogenesis are not
      known. Using laser microdissection and targeted gene misexpression in the chicken
      DM, we show that Pitx2-specific effectors mediate Wnt signaling to activate the
      formin Daam2, a key Wnt effector and itself a Pitx2 target, linking actin
      dynamics to cadherin-based junctions to ultimately generate asymmetric cell
      behaviors. Our work highlights how integration of two conserved cascades may be
      the ultimate force through which Pitx2 sculpts L-R organs. 

PMID- 24091018
TI  - The burden of leprosy in children and adolescents in rural southern Ethiopia.
AB  - BACKGROUND: Childhood leprosy has an important bearing on the epidemiology of
      disease and reflects the level of control in a community. There is limited
      information about this disease in rural Ethiopia. SUBJECTS AND METHODS: Data were
      collected retrospectively from leprosy patient records and treatment cards in a
      rural mission hospital in southern Ethiopia from 1999 to 2011. RESULTS: Over the
      13-year period, 298 patients with leprosy were registered for treatment. Of
      these, 22 (7.4%) were children (under 15 years) and 66 (21.1%) were adolescents
      (from 15 to 18 years). The male:female ratio was 2.6:1 in children and 1.7:1 in
      adolescents. Slit skin examination was positive in eight of 15 (36.4%) child
      patients and in 26 of 53 (41.3%) adolescents. Multibacillary leprosy was the most
      common type in both age groups, encountered in 95.5% of children and in 84.1% of
      adolescents. Six (27.3%) children and 18 (28.6%) adolescents had deformities of
      the hand, feet or eyes (WHO grade II), detected either at the time of diagnosis
      or during follow-up. Sixty-one per cent of children were transferred to their
      health institutions for treatment and follow-up; seven children (38.9%) completed
      the treatment and one (5.9%) defaulted while on therapy. Of 63 adolescent
      patients, 31 (49.2%) completed the recommended therapy, 28 (44.4%) were
      transferred out, and four (6.3%) defaulted on therapy. CONCLUSION: Childhood
      leprosy continues to be a common problem in rural southern Ethiopia.
      Multibacillary disease and disabilities remain common in children. Early
      detection and treatment of cases including the study of contacts should reduce
      the burden of leprosy in the community.

PMID- 24091020
TI  - The fading affect bias across alcohol consumption frequency for alcohol-related
      and non-alcohol-related events.
AB  - The Fading Affect Bias (FAB) is the tendency for unpleasant emotions to fade more
      over time than pleasant emotions (Walker, Vogl, & Thompson, 1997). The FAB is
      negatively related to dysphoria (Walker, Skowronski, Gibbons, Vogl, & Thompson,
      2003), which led researchers to suggest that the FAB is a healthy coping
      mechanism that improves the overall positivity of life (Walker, Skowronski, &
      Thompson, 2003). The FAB may also reinforce certain maladaptive behaviors, such
      as drinking alcohol, as the unpleasant emotions associated with those behaviors
      quickly fade from memory, and increase the likelihood of those behaviors in the
      future. If the FAB increases the likelihood of maladaptive alcohol consumption,
      the FAB should be greatest for ordinary events at low alcohol consumption levels,
      whereas the FAB should be greatest for alcohol events at high alcohol consumption
      levels. The results of two studies provided support for the hypotheses. The
      implications are discussed. 

PMID- 24091019
TI  - Use of cellobiohydrolase-free cellulase blends for the hydrolysis of
      microcrystalline cellulose and sugarcane bagasse pretreated by either ball
      milling or ionic liquid [Emim][Ac].
AB  - This study investigated the requirement of cellobiohydrolases (CBH) for
      saccharification of microcrystalline cellulose and sugarcane bagasse pretreated
      either by ball milling (BM) or by ionic liquid (IL) [Emim][Ac]. Hydrolysis was
      done using CBH-free blends of Pyrococcus horikoshii endoglucanase (EG) plus
      Pyrococcus furiosus beta-glucosidase (EGPh/BGPf) or OptimashTM BG while
      Acremonium Cellulase was used as control. IL-pretreated substrates were
      hydrolyzed more effectively by CBH-free enzymes than were the BM-pretreated
      substrates. IL-treatment decreased the crystallinity and increased the specific
      surface area (SSA), whereas BM-treatment decreased the crystallinity without
      increasing the SSA. The hydrolysis of IL-treated cellulose by EGPh/BGPf showed a
      saccharification rate of 3.92 g/Lh and a glucose yield of 81% within 9h. These
      results indicate the efficiency of CBH-free enzymes for the hydrolysis of IL
      treated substrates.

PMID- 24091021
TI  - Mammalian target of rapamycin inhibitors: the beginning of the end or the end of
      the beginning?

PMID- 24091022
TI  - Take a PAUSE for the premature ejaculation cause.

PMID- 24091023
TI  - Handedness: a neurogenetic shift of perspective.
AB  - Handedness is the single most studied aspect of human brain asymmetries. For long
      it has been thought to be a monogenic trait that can produce an asymmetrical
      shift of cerebral mechanisms, thereby producing right handedness. Nevertheless, a
      single gene explaining a sufficient amount of phenotypic variance has not been
      identified. The results of several recent studies using advanced molecular
      genetic techniques suggest that a multifactorial model taking into account both
      multiple genetic and environmental factors, as well as their interactions, might
      be better suited to explain the complex processes underlying the ontogenesis of
      handedness. In this article, we review the new insights into handedness genetics
      provided by these studies and discuss, how integrating results from genetic and
      neuroscientific studies might help us to generate more accurate models of the
      ontogenesis of handedness. Based on these thoughts, we suggest several candidate
      gene groups (e.g. genes involved in the formation of the corpus callosum,
      asymmetrically expressed genes or genes involved in the development of structural
      left-right asymmetries) whose investigation would help to further understand the
      complex relation of genes, the brain and handedness. 

PMID- 24091024
TI  - Zebrafish as a novel model to assess Na+/K(+)-ATPase-related neurological
      disorders.
AB  - Modeling neurological disorders using zebrafish increases rapidly as this model
      system allows easy access to all developmental stages and imaging of pathological
      processes. A surprising degree of functional conservation has been demonstrated
      between human genes implicated in neurodegenerative diseases and their zebrafish
      orthologues. Zebrafish offers rapid high throughput screening of therapeutic
      compounds and live imaging of pathogenic mechanisms in vivo. Several recent
      zebrafish studies functionally assessed the role of the sodium-potassium pump
      (Na(+)/K(+)-ATPase). The Na(+)/K(+)-ATPase maintains the electrochemical
      gradients across the plasma membrane, essential for e.g. signaling, secondary
      active transport, glutamate re-uptake and neuron excitability in animal cells.
      Na(+)/K(+)-ATPase mutations are associated with neurological disorders, where
      mutations in the Na(+)/K(+)-ATPase alpha2 and alpha3 isoforms cause Familial
      hemiplegic migraine type 2 (FHM2) and Rapid-onset dystonia-parkinsonism
      (RDP)/Alternating hemiplegic childhood (AHC), respectively. In zebrafish, knock
      down of Na(+)/K(+)-ATPase isoforms included skeletal and heart muscle defects,
      impaired embryonic motility, depolarized Rohon-beard neurons and abrupt brain
      ventricle development. In this review, we discuss zebrafish as a model to assess
      Na(+)/K(+)-ATPase isoform functions. Furthermore, studies investigating proteomic
      changes in both alpha2- and alpha3-isoform deficient embryos and their potential
      connections to the Na(+)/K(+)-ATPase functions will be discussed. 

PMID- 24091025
TI  - Antifungal resistance does not necessarily affect Candida glabrata fitness.
AB  - Although there has been an overall good coverage of Candida glabrata infections
      by the echinocandins, emergence of antifungal resistance during therapy has been
      reported. We investigated, by using an invertebrate host model, the fitness of
      sequential C. glabrata isolates with different echinocandins susceptibility
      patterns. The studied strains were isolated from a case of recurrent fungemia
      with a fatal outcome due to C. glabrata that developed cross-resistance to
      echinocandins during caspofungin therapy. The sequential strains isolated post
      therapy showed a S663P mutation in the Fks2p hot spot 1. In vivo study in the
      invertebrate host Galleria mellonella did not suggest a fitness cost related to
      the acquired antifungal resistance, the three isolates displayed a similar rate
      of killing (P  =  0.54). We observed a clear correlation between emergence of
      antifungal resistance and persistence of the causal agent, probably aided by the
      unchanged fitness and unresponsiveness in vivo to the adopted therapy.

PMID- 24091026
TI  - New clinical tests: let's get down in the weeds.

PMID- 24091027
TI  - Maternal carriage of extended-spectrum beta-lactamase-producing Escherichia coli
      isolates in Argentina.
AB  - The aim of this study was to determine the prevalence of vaginal Escherichia coli
      colonization and perianal carriage of Enterobacteriaceae resistant to third
      generation cephalosporins in pregnant women. Vaginal and perianal samples from
      259 pregnant women were studied. Vaginal swabs were inoculated onto MacConkey
      agar plates and perianal swabs were inoculated onto CHROMagar extended-spectrum
      beta-lactamase (ESBL) plates. The minimal inhibitory concentration of the
      isolates was determined using the Epsilometer test method. The phenotypic
      detection of ESBLs was performed by the combined disc method using cefotaxime
      versus cefotaxime plus clavulanate. The prevalence of vaginal E. coli
      colonization during pregnancy was 14.3%. The resistance rate to ampicillin,
      gentamicin, and cefotaxime was 48.6, 10.8, and 0.8%, respectively.
      Enterobacteriaceae resistant to third generation cephalosporins were recovered in
      7.3% of all perianal specimens. Among them, 5.4% of pregnant women were colonized
      with E. coli ESBL-producer strains. The present study revealed that colonization
      with Enterobacteriaceae resistant to third generation cephalosporins is
      significant in pregnancy. ESBL-producing E. coli were the most prevalent
      organisms. Screening strategies designed to monitor for ESBL-producing E. coli
      could be useful in endemic areas to prevent perinatal transmission and the
      introduction of multiresistant strains to the maternity ward.

PMID- 24091029
TI  - EGFR and microvessel density in canine malignant mammary tumours.
AB  - The epidermal growth factor receptor (EGFR) is a transmembrane tyrosine kinase
      receptor which has been shown to have an important role in human breast cancer.
      Its role appears to be associated with increased angiogenesis and metastasis. In
      order to clarify its role in canine mammary tumours (CMT), 61 malignant neoplasms
      were studied by using immunohistochemistry, comparing expression of EGFR,
      microvessel density (MVD) by CD31 immunolabelling and characteristics of tumour
      aggressiveness. High EGFR immunoexpression was statistically significantly
      associated with tumour size, tumour necrosis, mitotic grade, histological grade
      of malignancy and clinical stage. High CD31 immunoreactivity was statistically
      significantly associated with tubule formation, histological grade of malignancy
      and clinical stage. A positive correlation between EGFR and CD31 immunoexpression
      (r = 0.843; P < 0.001) was also observed. Results suggest that an over-expression
      of EGFR may contribute to increased angiogenesis and aggression in malignant CMT,
      presenting the possibility of using EGFR inhibitors in the context of metastatic
      disease treatment.

PMID- 24091028
TI  - ALK as a paradigm of oncogenic promiscuity: different mechanisms of activation
      and different fusion partners drive tumors of different lineages.
AB  - Anaplastic lymphoma kinase (ALK) is a receptor tyrosine kinase protein implicated
      in a variety of hematological malignancies and solid tumors. Since the
      identification of the ALK gene in 1994 as the target of the t(2;5) chromosomal
      translocation in anaplastic large cell lymphoma, ALK has been proven a remarkably
      promiscuous oncogene. ALK contributes to the development of a notable assortment
      of tumor types from different lineages, including hematolymphoid, mesenchymal,
      epithelial and neural tumors, through a variety of genetic mechanisms: gene
      fusions, activating point mutations, and gene amplification. Recent developments
      led to significant diagnostic and therapeutic advances, including efficient
      diagnostic tests and ALK-targeting agents readily available in the clinical
      setting. This review addresses some therapeutic considerations of ALK-targeted
      agents and the biologic implications of ALK oncogenic promiscuity, but the main
      points discussed are: 1) the variety of mechanisms that result in activation of
      the ALK oncogene, with emphasis on the promiscuous partnerships demonstrated in
      chromosomal rearrangements; 2) the diversity of tumor types of different lineages
      in which ALK has been implicated as a pathogenic driver; and 3) the different
      diagnostic tests available to identify ALK-driven tumors, and their respective
      indications. 

PMID- 24091030
TI  - Does anaerobic bacterial antibiosis decrease fungal diversity in oral
      necrobacillosis disease?
AB  - Oral necrobacillosis (ON) is a model polymicrobial disease that affects macropods
      in captivity and livestock. Several studies in humans and animals have focused
      mainly on the bacterial etiology of this disease with little or no information on
      the role/association of fungi with ON. Using a Polymerase Chain Reaction
      Denaturing Gradient Gel Electrophoresis (PCR-DGGE) assay and statistical analysis
      of the fungal community structure in healthy and disease groups, a reduction in
      the species diversity and drastic reduction (>1000 fold) in the fungal population
      in wallabies with ON was observed. Furthermore, an in vitro assay revealed a
      potential anaerobic-bacteria antibiosis mechanism in the observed decrease in
      fungal population in ON and a synergistic bacterial-fungal interaction in
      wallabies with healthy oral status. This study contributes to our knowledge of
      the fungal community structure associated with ON and forms the basis for an
      investigation at an epidemiological scale in order to exploit the clinical
      potentials of these findings. 

PMID- 24091031
TI  - The association between asthma and diabetes: does it exist?

PMID- 24091032
TI  - An unusual pedestrian road trauma: from forensic pathology to forensic veterinary
      medicine.
AB  - Traffic accidents have increased in the last decade, pedestrians being the most
      affected group. At autopsy, it is evident that the most common cause of
      pedestrian death is central nervous system injury, followed by skull base
      fractures, internal bleeding, lower limb haemorrhage, skull vault fractures,
      cervical spinal cord injury and airway compromise. The attribution of accident
      responsibility can be realised through reconstruction of road accident dynamics,
      investigation of the scene, survey of the vehicle involved and examination of the
      victim(s). A case study concerning a car accident where both humans and pets were
      involved is reported here. Investigation and reconstruction of the crime scene
      were conducted by a team consisting of forensic pathologists and forensic
      veterinarians. At the scene investigation, the pedestrian and his dog were
      recovered on the side of the road. An autopsy and a necropsy were conducted on
      the man and the dog, respectively. In addition, a complete inspection of the
      sports utility vehicle (SUV) implicated in the road accident was conducted. The
      results of the autopsy and necropsy were compared and the information was used to
      reconstruct the collision. This unusual case was solved through the collaboration
      between forensic pathology and veterinary forensic medicine, emphasising the
      importance of this kind of co-operation to solve a crime scene concerning both
      humans and animals. 

PMID- 24091033
TI  - A short version of the measurement and treatment research to improve cognition in
      schizophrenia consensus cognitive battery.

PMID- 24091035
TI  - Jumping to conclusions and delusions: the impact of discussion of the bias on the
      bias.
AB  - The present study was an investigation of the impact a brief intervention
      designed to raise awareness of a cognitive bias known to be robust for
      individuals with delusions has on the reasoning strategies of individuals with
      delusions. Individuals with delusions (n=57) were randomly assigned either to
      receive or not to receive a discussion of the jumping to conclusions bias and its
      pitfalls. Participants' performance on 3 reasoning trials - 1 emotionally neutral
      (beads) and 2 emotionally salient (self-referred survey words) - was then
      assessed; the number of stimuli participants requested before making a decision
      was evaluated to determine if the Jumping to Conclusions Discussion resulted in
      increased data gathering. There was no difference between groups (those who
      received and those who did not receive the Jumping to Conclusions Discussion) in
      terms of how many beads they gathered (p=.36), but there were significant
      differences on both reasoning trials of emotionally salient stimuli (p's<.05),
      such that participants who received the Jumping to Conclusions Discussion
      requested more stimuli on those tasks than individuals who did not receive the
      discussion. Thus, results suggest that discussion of the jumping to conclusions
      bias may impact the bias directly, at least for material that is emotional in
      nature. Results are discussed in terms of their relevance to cognitive behavioral
      therapies for psychosis and existing research on reasoning and delusions. 

PMID- 24091036
TI  - Decoding facial blends of emotion: visual field, attentional and hemispheric
      biases.
AB  - Most clinical research assumes that modulation of facial expressions is
      lateralized predominantly across the right-left hemiface. However, social
      psychological research suggests that facial expressions are organized
      predominantly across the upper-lower face. Because humans learn to cognitively
      control facial expression for social purposes, the lower face may display a false
      emotion, typically a smile, to enable approach behavior. In contrast, the upper
      face may leak a person's true feeling state by producing a brief facial blend of
      emotion, i.e. a different emotion on the upper versus lower face. Previous
      studies from our laboratory have shown that upper facial emotions are processed
      preferentially by the right hemisphere under conditions of directed attention if
      facial blends of emotion are presented tachistoscopically to the mid left and
      right visual fields. This paper explores how facial blends are processed within
      the four visual quadrants. The results, combined with our previous research,
      demonstrate that lower more so than upper facial emotions are perceived best when
      presented to the viewer's left and right visual fields just above the horizontal
      axis. Upper facial emotions are perceived best when presented to the viewer's
      left visual field just above the horizontal axis under conditions of directed
      attention. Thus, by gazing at a person's left ear, which also avoids the social
      stigma of eye-to-eye contact, one's ability to decode facial expressions should
      be enhanced. 

PMID- 24091034
TI  - The effect of transient increases in kynurenic acid and quinolinic acid levels
      early in life on behavior in adulthood: Implications for schizophrenia.
AB  - Kynurenic acid is a tryptophan metabolite that is synthesized and released in the
      brain by astrocytes and acts as an antagonist of nicotinic acetylcholine
      receptors and N-methyl-d-aspartate glutamate receptors, both of which are
      critically involved in cognition as well as neural plasticity and brain
      development. The concentration of kynurenic acid is increased in the brains of
      persons with schizophrenia and this increase has been implicated in the cognitive
      and social impairments associated with the disease. In addition, growing evidence
      suggests that the increase in kynurenic acid may begin early in life. For
      example, exposure to influenza A virus during development results in a transient
      increase in kynurenic acid concentration that could disrupt normal brain
      development and lead to cognitive deficits later in life. Changes in kynurenic
      acid may thus provide a link between developmental exposure to viruses and the
      increased risk of subsequently developing schizophrenia. To test this, we
      mimicked the effects of influenza A exposure by treating rats with kynurenine,
      the precursor of kynurenic acid, on postnatal days 7-10. We observed a transient
      increase in both kynurenic acid and quinolinic acid during treatment. When rats
      were subsequently behaviorally tested as adults, those previously treated with
      kynurenine exhibited decreased social behavior and locomotor activity. In
      contrast, attentional function and fear conditioning were not affected. Together
      with other recent findings, these data have several implications for
      understanding how viral-induced changes in tryptophan metabolism during
      development may contribute to schizophrenia-related symptoms later in life. 

PMID- 24091037
TI  - The effect of antiepileptic drugs on thyroid function in children.
AB  - BACKGROUND: Limited and conflicting data exist for the influence of antiepileptic
      drugs on thyroid function in children. OBJECTIVE: The aim of this study was to
      investigate the effects of phenobarbital, valproate, carbamazepine,
      oxcarbazepine, and levetiracetam monotherapy on thyroid function in daily
      clinical practice during a 12-month treatment period. METHOD: A total of 223
      children (103 females and 120 males) with new onset and controlled epilepsy
      treated with valproate (n=129), phenobarbital (n=33), carbamazepine (n=36),
      oxcarbazepine (n=14), levetiracetam (n=11) were enrolled in the study. Serum free
      thyroxine (fT4) and thyroid-stimulating hormone (TSH) levels were measured before
      and at first, sixth and twelfth months of therapy. RESULTS: At baseline, average
      fT4 and TSH concentrations were not different between the drug groups. Valproate
      treated patients had decreased fT4 and increased TSH levels at months 1, 6, and
      12. Carbamazepine-treated patients had decreased fT4 levels at months 1, 6, and
      12 and increased TSH levels at months 1, and 6. Phenobarbital-treated patients
      had decreased fT4 levels at months 1, and 6, and increased TSH levels at months 6
      and 12. Oxcarbazepine-treated patients had decreased fT4 levels at month 1.
      Levetiracetam-treated patients showed no significant change of fT4 and TSH at any
      times. The frequency of subclinical hypothyroidism at month 12 was 28% in
      valproate, 21.4% in oxcarbazepine, 18.2% in phenobarbital, 13.9% in
      carbamazepine, and 0% in levetiracetam groups. CONCLUSION: Our data suggest that
      all antiepileptic drugs studied except levetiracetam had varying degrees of
      deleterious effects on thyroid function.

PMID- 24091038
TI  - Quantitative morphological analysis of arrestin2 clustering upon G protein
      coupled receptor stimulation by super-resolution microscopy.
AB  - Clustering of arrestins upon G protein-coupled receptor stimulation is a
      phenomenon that is well-known but difficult to describe quantitatively due to the
      size of the clusters close to the diffraction limit of visible light. We
      introduce a general method to quantitatively investigate the clustering of
      arrestin following stimulation of the C-C chemokine receptor 5 (CCR5) using
      single-molecule super-resolution imaging and coordinate and image-based cluster
      analysis. We investigated the effect of potent anti-HIV ligands of CCR5 with
      different pharmacological profiles on arrestin2 cluster formation and found that
      only the ligands capable of inducing CCR5 internalization induced arrestin2
      recruitment and clustering. We further demonstrate that the fraction of arrestin2
      molecules found in clusters larger than 100nm correlates with the magnitude of
      ligand-induced CCR5 internalization, but not with G protein activation,
      indicating that recruitment of arrestin2 to CCR5 is independent of G protein
      activation. Pre-treatment of the cells with the drug cytochalasin D, which blocks
      actin polymerization, led to the formation of larger clusters, whereas the
      inhibitor of microtubule polymerization nocodazole had little effect on arrestin2
      recruitment, suggesting an active role of actin in the organization and dynamics
      of these aggregates. 

PMID- 24091039
TI  - Characterization of crocodile teeth: correlation of composition, microstructure,
      and hardness.
AB  - Structure and composition of teeth of the saltwater crocodile Crocodylus porosus
      were characterized by several high-resolution analytical techniques. X-ray
      diffraction in combination with elemental analysis and infrared spectroscopy
      showed that the mineral phase of the teeth is a carbonated calcium-deficient
      nanocrystalline hydroxyapatite in all three tooth-constituting tissues: Dentin,
      enamel, and cementum. The fluoride content in the three tissues is very low (<0.1
      wt.%) and comparable to that in human teeth. The mineral content of dentin,
      enamel, and cementum as determined by thermogravimetry is 71.3, 80.5, and 66.8
      wt.%, respectively. Synchrotron X-ray microtomography showed the internal
      structure and allowed to visualize the degree of mineralization in dentin,
      enamel, and cementum. Virtual sections through the tooth and scanning electron
      micrographs showed that the enamel layer is comparably thin (100-200 MUm). The
      crystallites in the enamel are oriented perpendicularly to the tooth surface. At
      the dentin-enamel-junction, the packing density of crystallites decreases, and
      the crystallites do not display an ordered structure as in the enamel. The
      microhardness was 0.60+/-0.05 GPa for dentin, 3.15+/-0.15 GPa for enamel, 0.26+/
      0.08 GPa for cementum close to the crown, and 0.31+/-0.04 GPa for cementum close
      to the root margin. This can be explained with the different degree of
      mineralization of the different tissue types and is comparable with human teeth.

PMID- 24091041
TI  - Have you googled today?

PMID- 24091040
TI  - Biosorption of Cd(II) from aqueous solution using xanthated nano banana
      cellulose: equilibrium and kinetic studies.
AB  - Present study explored the biosorption capacity of xanthated nano banana
      cellulose (XNBC) for Cd(II) from aqueous solution. The biosorbent containing
      sulfur-bearing groups have a high affinity for heavy metals. Sulfur can be
      considered as a soft ligand group having strong affinity for cadmium. In the
      present study, the influence of various important parameters such as pH, time,
      biosorbent dose and initial Cd(II) concentration on the biosorption capacity were
      investigated. The maximum biosorption capacity of XNBC for Cd(II) was found to be
      154.26 mg g-1 at 298 K. The Cd(II) sorption of XNBC was confirmed by SEM-EDS and
      XRF analysis. The isotherms such as Langmuir, Freundlich, Redlich-Peterson and
      Tempkin were studied. The Langmuir and the Redlich-Peterson isotherms had been
      well fitted the biosorption of Cd(II) with xanthated nano banana cellulose. The
      kinetics of Cd(II) removal using XNBC was well explained by second-order kinetic
      model. The thermodynamic parameters were also evaluated from the biosorption
      measurements. Among the various desorbing agents tested, the desorbing efficiency
      was found to be maximum with 0.1 mol L-1 HCl. It was found that XNBC is also
      suitable to be used under column operation.

PMID- 24091042
TI  - The Oregon trial.

PMID- 24091043
TI  - Combined radiology residency-PhD program: 10-year review of program results.

PMID- 24091044
TI  - ACR appropriateness criteria palpable breast masses.
AB  - A palpable breast mass is one of the most common presenting features of breast
      carcinoma. However, the clinical features are frequently nonspecific. Imaging
      performed before biopsy is helpful in characterizing the nature of the mass. For
      women with clinically detected breast masses, the vast majority will require
      evaluation with ultrasound. Diagnostic mammography is the initial imaging
      modality of choice for women aged >= 40 years; ultrasound is typically necessary
      unless a definitively benign mass is identified as the etiology of the clinical
      finding. For evaluating women aged <30 years and women who are pregnant or
      lactating, ultrasound is used for initial evaluation. For women aged 30 to 39
      years, either ultrasound or diagnostic mammography may be used for initial
      evaluation. MRI is rarely indicated to evaluate a clinically detected finding.
      Biopsy is indicated for masses with suspicious features. Short-term follow-up is
      a reasonable alternative to biopsy for solid masses with probably benign features
      suggesting fibroadenoma. Correlation between imaging and the clinical finding is
      essential. 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- 24091045
TI  - The 2013 ACR Commission on Human Resources workforce survey.
AB  - BACKGROUND: The ACR Commission on Human Resources conducts an annual electronic
      survey during the first quarter of the year to better understand the present
      workforce situation for radiologists. METHODS: We used the Practice of Radiology
      Environment Database (PRED) to identify 2,067 practice leaders and asked them to
      complete an electronic survey developed by the Commission on Human Resources. The
      survey asked group leaders or their designates to report the number of
      radiologists they currently employ or supervise, the number hired in 2012, and
      the number they plan to hire in 2013 and 2016. The leaders were also asked to
      report the subspecialty area that was used as the main reason for hiring that
      physician. RESULTS: Of the 2,067 practice leaders surveyed, 22% responded, a
      figure corresponding to 23% of all practicing radiologists in the United States.
      These results showed that 54% of radiologists are in private practice and 46% are
      employed by various other entities. The current workforce consists of 21% general
      radiologists and 79% subspecialists. The largest areas of subspecialty include
      general interventionalists, neuroradiologists, and body imagers. In 2012, 1,407
      radiologists were hired. The greatest number of radiologists hired involved
      general interventional radiologists, followed by general radiologists, body
      imagers, and those specializing in musculoskeletal radiology, neuroradiology, and
      breast imaging. In 2013, 1,526 job opportunities were projected and in 2016,
      1,434 job opportunities. In 2013, the most sought-after individuals will be
      general radiologists, general interventionalists, breast imagers,
      neuroradiologists, musculoskeletal radiologists, and body imagers. CONCLUSION:
      Based on the data collected from the responding practices, the demand for hiring
      radiologists in 2013 will be similar to 2012. Each of the 1,200 residents who
      complete their training programs each year should have a position available, but
      the job may not necessarily be in the subspecialty, geographic area, or type of
      practice that the individual desires.

PMID- 24091046
TI  - Are we training the right number of radiologists?

PMID- 24091047
TI  - The increasing role of radiologists in thoracic diagnosis: more thoracic biopsies
      are performed percutaneously.
AB  - PURPOSE: The rate of thoracic biopsies overall and by type of biopsy from 1998 to
      2010 is not known. The aim of this study was to examine the utilization rate of
      various types of thoracic biopsies within the Medicare population. METHODS:
      Source data was obtained from the CMS Physician/Supplier Procedure Summary Master
      Files from 1998 to 2010. Allowed primary claims submitted for percutaneous
      thoracic biopsy, bronchoscopic thoracic biopsy, and surgical thoracic biopsy were
      extracted. Annual volume and utilization rates were calculated and analyzed by
      biopsy type and provider type. RESULTS: Total thoracic biopsy volume in 1998 was
      176,125 and in 2010 was 167,911 (-4.7%). The utilization rate for all thoracic
      biopsies decreased from 5.47 per 1,000 in 1998 to 4.76 per 1,000 (-13.0%) in
      2010. The percutaneous biopsy utilization rate increased 3.6% from 1998 to 2010,
      while the rate for surgical biopsy decreased by 20.9% and the rate of
      bronchoscopic biopsy decreased by 19.6% during the same time period. In 2010,
      radiologists performed 96.4% (58,679) of all percutaneous biopsies. Radiologists'
      thoracic biopsy market share increased from 26.2% (46,084 of 176,125) in 1998 to
      35.0% (58,700 of 167,911) in 2010 (+33.6%). CONCLUSIONS: The overall rate of
      thoracic biopsy decreased from 1998 to 2010, with fewer biopsies being performed
      surgically and bronchoscopically and more biopsies being performed
      percutaneously. Radiologists are responsible for an increasing role in thoracic
      diagnosis, as they have increased market share of thoracic biopsies. These
      findings may be the result of changing trends toward less invasive procedures,
      changing patterns of reimbursement, and increased availability of percutaneous
      biopsy.

PMID- 24091048
TI  - The Image Gently pediatric digital radiography safety checklist: tools for
      improving pediatric radiography.
AB  - Transition from film-screen to digital radiography requires changes in
      radiographic technique and workflow processes to ensure that the minimum
      radiation exposure is used while maintaining diagnostic image quality. Checklists
      have been demonstrated to be useful tools for decreasing errors and improving
      safety in several areas, including commercial aviation and surgical procedures.
      The Image Gently campaign, through a competitive grant from the FDA, developed a
      checklist for technologists to use during the performance of digital radiography
      in pediatric patients. The checklist outlines the critical steps in digital
      radiography workflow, with an emphasis on steps that affect radiation exposure
      and image quality. The checklist and its accompanying implementation manual and
      practice quality improvement project are open source and downloadable at
      www.imagegently.org. The authors describe the process of developing and testing
      the checklist and offer suggestions for using the checklist to minimize radiation
      exposure to children during radiography. 

PMID- 24091049
TI  - Managing incidental findings on abdominal and pelvic CT and MRI, Part 2: white
      paper of the ACR Incidental Findings Committee II on vascular findings.
AB  - This white paper describes vascular incidental findings found on CT and MRI of
      the abdomen and pelvis. Recommendations for management are included. This
      represents the second of 4 such papers from the ACR Incidental Findings Committee
      II, which used a consensus method based on repeated reviews and revisions and a
      collective review and interpretation of relevant literature. Topics include
      definitions and recommended management for abdominal aortic, iliac, splenic,
      renal, and visceral artery aneurysms. Other incidentally discovered aortic
      conditions, systemic venous anomalies, compression syndromes, abdominal venous
      thrombosis, and gonadal and pelvic venous conditions are also discussed. A table
      is provided for reference. 

PMID- 24091050
TI  - Strategies for dealing with the radiology faculty shortage in Pakistan.

PMID- 24091051
TI  - Paul C. Hodges.

PMID- 24091052
TI  - Limitations and challenges in treatment of acute chemical warfare agent
      poisoning.
AB  - Recent news from Syria on a possible use of chemical warfare agents made the
      headlines. Furthermore, the motivation of terrorists to cause maximal harm shifts
      these agents into the public focus. For incidents with mass casualties
      appropriate medical countermeasures must be available. At present, the most
      important threats arise from nerve agents and sulfur mustard. At first, self
      protection and protection of medical units from contamination is of utmost
      importance. Volatile nerve agent exposure, e.g. sarin, results in fast
      development of cholinergic crisis. Immediate clinical diagnosis can be confirmed
      on-site by assessment of acetylcholinesterase activity. Treatment with
      autoinjectors that are filled with 2mg atropine and an oxime (at present
      obidoxime, pralidoxime, TMB-4 or HI-6) are not effective against all nerve
      agents. A more aggressive atropinisation has to be considered and more effective
      oximes (if possible with a broad spectrum or a combination of different oximes)
      as well as alternative strategies to cope with high acetylcholine levels at
      synaptic sites should be developed. A further gap exists for the treatment of
      patients with sustained cholinergic crisis that has to be expected after exposure
      to persistent nerve agents, e.g. VX. The requirement for long-lasting artificial
      ventilation can be reduced with an oxime therapy that is optimized by using the
      cholinesterase status for guidance or by measures (e.g. scavengers) that are able
      to reduce the poison load substantially in the patients. For sulfur mustard
      poisoning no specific antidote is available until now. Symptomatic measures as
      used for treatment of burns are recommended together with surgical or laser
      debridement. Thus, huge amounts of resources are expected to be consumed as wound
      healing is impaired. Possible depots of sulfur mustard in tissues may aggravate
      the situation. More basic knowledge is necessary to improve substantially
      therapeutic options. The use of stem cells may provide a new and promising
      option. 

PMID- 24091053
TI  - The revised sleeve gastrectomy: technical considerations.

PMID- 24091054
TI  - Comment on: Longitudinal trends in hedonic hunger following Roux-en-Y gastric
      bypass in adolescents.

PMID- 24091055
TI  - Vitamin B12 deficiency in patients undergoing bariatric surgery: preventive
      strategies and key recommendations.
AB  - BACKGROUND: Advances in bariatric surgery have brought about a paradigm shift in
      the management of obesity, with benefits extending beyond weight loss. However,
      nutritional deficiencies are an inherent problem in the postoperative period and
      often require lifelong supplementation. Vitamin B12, also referred to as
      cobalamin, is one of the most common micronutrient deficiencies affecting this
      population. This review explores the pathophysiology of cobalamin deficiency in
      patients undergoing bariatric surgery and provides an overview of the
      effectiveness of various available vitamin B12 formulations. METHODS: To identify
      the relevant literature, a systematic review of MEDLINE was conducted from the
      earliest dates through September 2012 for English-language articles describing
      the prevention and management of vitamin B12 deficiency in patients undergoing
      bariatric surgery. RESULTS: Intramuscular vitamin B12 continues to be the gold
      standard of therapy for vitamin B12 deficiency, especially in symptomatic
      patients. In select patients with asymptomatic vitamin B12 deficiency after Roux
      en-Y gastric bypass (RYGB), high-dose oral cyanocobalamin should be given a
      consideration, especially when there are concerns with the adherence to
      intramuscular therapy or if compliance comes into question. Unlike patients post
      RYGB, those undergoing restrictive procedures such as gastric banding and sleeve
      gastrectomy may be maintained postoperatively on a lower-dose daily vitamin B12
      supplementation. Efficacy data of nasal and sublingual routes for maintenance
      therapy is currently awaited. CONCLUSION: Patients undergoing bariatric surgery
      must be continuously educated on proper nutrition, the risk of developing
      significant vitamin B12 deficiency, and the role of supplements in avoiding
      catastrophic consequences.

PMID- 24091056
TI  - Comment on: Aortic injuries during laparoscopic gastric bypass for morbid obesity
      in Sweden 2009-2010: a nationwide survey.

PMID- 24091057
TI  - Comment on: Safety and efficacy of laparoscopic adjustable gastric banding in
      patients aged seventy and older.

PMID- 24091058
TI  - Mitochondrial D310 D-Loop instability and histological subtypes in radiation
      induced cutaneous basal cell carcinomas.
AB  - BACKGROUND: Basal cell carcinoma (BCC) is the most frequent skin cancer. An
      elevated prevalence of BCC has been associated with radiation, namely after the
      Tinea capitis epilation treatment, being these tumors described as more
      aggressive. Mitochondrial DNA (mtDNA) mutations have been reported in many human
      tumors, but their occurrence in BCC is poorly documented. OBJECTIVE: The purpose
      of this work was to evaluate BCC histological subtypes in individuals subjected
      to X-ray epilation for Tinea capitis treatment when compared to non-irradiated
      patients. Moreover we also wanted to evaluate mitochondrial D-Loop instability in
      both groups of BCCs in order to compare the frequency of D-Loop mutations in post
      irradiation BCC versus sporadic BCC. METHODS: 228 histological specimens
      corresponding to BCCs from 75 irradiated patients and 60 non-irradiated patients
      were re-evaluated for histological subtype. Subsequently, we sequenced the D-Loop
      310 repeat in blood, oral mucosa, tumor lesions and, whenever available, non
      tumoral adjacent tissue from these patients. RESULTS: The infiltrative subtype of
      BCC, considered to be more aggressive, was significantly more frequent in
      irradiated patients. BCC D-Loop D310 mutation rate was significantly higher in
      irradiated BCCs than in the non-irradiated ones. Moreover, it was associated with
      a higher irradiation dose. The presence of mtDNA heteroplasmy in patients' blood
      was associated with a higher mutation rate in the BCCs suggesting that a more
      unstable genotype could predispose to mtDNA somatic mutation. CONCLUSIONS: Our
      results suggest that radiation-induced BCCs may be considered to be more
      aggressive tumors. Further studies are needed to clarify the role of mtDNA D-Loop
      mutations in tumors from irradiated patients.

PMID- 24091059
TI  - Roles of cilia, fluid flow, and Ca2+ signaling in breaking of left-right
      symmetry.
AB  - The emergence of left-right (L-R) asymmetry during embryogenesis is a classic
      problem in developmental biology. It is only since the 1990s, however, that
      substantial insight into this problem has been achieved by molecular and genetic
      approaches. Various genes required for L-R asymmetric morphogenesis in
      vertebrates have now been identified, and many of these genes are required for
      the formation and motility of cilia. Breaking of L-R symmetry in the mouse embryo
      occurs in the ventral node, where two types of cilia are present. Whereas
      centrally located motile cilia generate a leftward fluid flow, peripherally
      located immotile cilia sense a flow-dependent signal, which is either chemical or
      mechanical in nature. Although Ca2+ signaling is implicated in flow sensing, the
      precise mechanism remains unknown. Here we summarize current knowledge of L-R
      symmetry breaking in vertebrates (focusing on the mouse), with a special emphasis
      on the roles of cilia, fluid flow, and Ca2+ signaling.

PMID- 24091060
TI  - The intimate relationships of mRNA decay and translation.
AB  - The decay rate of an mRNA and the efficiency with which it is translated are key
      determinants of eukaryotic gene expression. Although it was once thought that
      mRNA stability and translational efficiency were directly linked, the
      interrelationships between the two processes are considerably more complex. The
      decay of individual mRNAs can be triggered or antagonized by translational
      impairment, and alterations in the half-life of certain mRNAs can even alter
      translational fidelity. In this review we consider whether mRNA translation and
      turnover are distinct or overlapping phases of an mRNA life cycle, and then
      address some of the many ways in which the two processes influence each other in
      eukaryotic cells. 

PMID- 24091061
TI  - Parent-administered exposure to increase children's vegetable acceptance: a
      randomized controlled trial.
AB  - BACKGROUND: Repeated taste exposure, in combination with small rewards, has been
      shown to increase children's acceptance of disliked foods. However, previous
      studies have used direct contact with researchers or professionals for the
      implementation of the repeated exposure procedure. If mailed taste exposure
      instructions to parents produced comparable outcomes, this could be a cost
      effective and easily disseminable strategy to promote healthier diets in
      children. OBJECTIVE: Our randomized controlled study aimed to test the efficacy
      and acceptability of mailed materials giving instructions on taste exposure as a
      means of increasing acceptance of vegetables in preschool-aged children. DESIGN:
      Participants were families of 3-year-old twins from the Gemini cohort who took
      part between March 2011 and April 2012. Families were randomized to a mailed
      intervention or a no treatment control condition. The intervention involved
      offering each child 14 daily tastes of a disliked (target) vegetable with a small
      reward (a sticker) if the child complied. MAIN OUTCOME MEASURES: Outcomes were
      the child's intake of the target vegetable (number of pieces) and parent reports
      of the child's liking at two baseline (T1 and T2) and one postintervention (T3)
      behavior assessment. RESULTS: Record sheets with intake and liking data from T1,
      T2, and T3 were returned for 472 children, of which 442 were complete (94%). Over
      the intervention period (T2 to T3) intake and liking of the target vegetable
      increased significantly more in the intervention group than in the control group
      (intake: odds ratio 12.05, 95% CI 8.05 to 18.03, P<0.001; liking: odds ratio
      12.34, CI 7.97 to 19.12, P<0.001). Acceptability of the procedure was very high
      among parents who completed the protocol. CONCLUSIONS: Mailed instructions for
      taste exposure were effective in increasing children's acceptance of an initially
      disliked vegetable. These results support the value of parent-administered
      exposure to increase children's vegetable acceptance, and suggest that it can be
      carried out without direct health professional contact.

PMID- 24091062
TI  - A fibrinogen-related protein (TfFREP2) gene involving in the immune response of
      Trachidermus fasciatus against Vibrio anguillarum.
AB  - Fibrinogen-related proteins play important roles in the immune responses. We have
      obtained a cDNA encoding a novel fibrinogen-related protein from roughskin
      sculpin Trachidermus fasciatus (T. fasciatus) and named it as TfFREP2. The N and
      C terminus of TfFREP2 contain a putative 21-amino acid signal peptide and a
      typical 217-amino acid fibrinogen-like domain, which is conserved in all
      fibrinogen-related proteins. TfFREP2 has three glycosylation sites and two
      potential calcium-binding sites that are possibly involved in calcium
      coordination. The results of tissue specific checking showed that the mRNA and
      protein of TfFREP2 were particularly abundant in skin and gill among all the
      tested tissues. TfFREP2 mRNA and protein expression changed significantly after
      being challenged by Vibrio anguillarum pathogen in those immune-barrier tissues,
      such as skin and gill. Furthermore, recombinant TfFREP2 is able to agglutinate
      and bind V. anguillarum in the presence of calcium ion. The above results suggest
      that TfFREP2 might be involved in the host defense of fish against V. anguillarum
      infection.

PMID- 24091063
TI  - A multicolour flow cytometry identifying defined leukocyte subsets of rainbow
      trout (Oncorhynchus mykiss).
AB  - The investigation of the cellular immune response in fish species has been for a
      long time hampered by absence of appropriate monoclonal antibodies (MAbs)
      recognising subset specific surface markers. Consequently, the majority of
      immunological studies still focus on the changes in total leukocyte numbers or
      describe gene pattern in lymphoid organs without any information about their
      cellular composition. Flow cytometric techniques are routinely used for the
      evaluation of the leukocyte composition in numerous vertebrate species and
      contributed significantly to the current knowledge of immune system. In rainbow
      trout is so far only a limited number of MAbs against characterised (IgM and IgT,
      CD8alpha) or unknown lineage markers on thrombocytes, myeloid cells or T cells
      available. By combination of several MAbs, we developed a rapid, simple, accurate
      and high throughput method for reliable discrimination of major leukocyte
      subpopulations from 10 MUl of peripheral blood. Additionally, by a consecutive
      gating, this mixture enables the evaluation of the proportion between CD8alpha(+)
      and CD8alpha(-) population and provides for the first time valuable information
      about the kinetic of CD4(+) cells in rainbow trout. Furthermore, the combination
      of all antibodies within one sample reduced the hands-on time down to 90 min
      allowing fast and accurate estimation of cell kinetics in a high number of
      individuals. Thus presented findings enable the precise evaluation of the
      cellular components of immune system during both pathological and physiological
      responses and have therefore an immense potential for future applications in the
      development of vaccines and better understanding of fish immune system.

PMID- 24091064
TI  - Characterization of LPS-induced TNFalpha factor (LITAF) from orange-spotted
      grouper, Epinephelus coioides.
AB  - Lipopolysaccharide-induced TNFalpha factor (LITAF) is an important transcription
      factor that mediates cell apoptosis and inflammatory response. In the present
      study, we cloned and characterized a LITAF gene from orange-spotted grouper
      (Epinephelus coioides) (Ec-LITAF). Ec-LITAF encoded a predicted 142 amino acid
      protein which shared 74% identity to sablefish (Anoplopoma fimbria) LITAF
      homolog. Multiple amino acid alignment showed that Ec-LITAF contained a typical
      LITAF domain with two CXXC motifs. Phylogenetic analysis indicated that Ec-LITAF
      was closely related to that of sablefish. Ec-LITAF mRNA was widely expressed in
      different tissues and its expression level in spleen was up-regulated after
      Singapore grouper iridovirus (SGIV) infection. Subcellular localization analysis
      revealed that the distribution of Ec-LITAF showed diffuse and aggregated patterns
      in cytoplasm. Interestingly, the distribution of Ec-LITAF overlayed with a viral
      LITAF homolog (vLITAF) encoded by SGIV. Overexpression of Ec-LITAF in vitro up
      regulated the expression of tumor necrosis factors (TNF1 and TNF2) and TNF
      receptors (TNFR1 and TNFR2), and the expression of itself initiated apoptosis in
      fish cells. In addition, overexpression of Ec-LITAF not only accelerated SGIV
      infection induced CPE and cell death, but also increased viral gene
      transcription. Taken together, our data suggested that Ec-LITAF might play
      crucial roles during SGIV replication. 

PMID- 24091065
TI  - Prenatal diagnosis of pure partial monosomy 18p associated with holoprosencephaly
      and congenital heart defects.
AB  - We applied CMA to detect chromosomal variations during a prenatal diagnosis and
      detected a 4.5Mb pure microdeletion at 18p11.3 that was not detected by
      conventional karyotyping. Fluorescent in situ hybridization (FISH) analysis was
      performed to confirm the deletion. Accurate breakpoints of the deletion in this
      patient were used to build correlations between monosomy 18p and the concomitant
      phenotypes, particularly holoprosencephaly (HPE), which is rarely reported in
      monosomy 18p11.3.

PMID- 24091066
TI  - Folate: metabolism, genes, polymorphisms and the associated diseases.
AB  - Folate being an important vitamin of B Complex group in our diet plays an
      important role not only in the synthesis of DNA but also in the maintenance of
      methylation reactions in the cells. Folate metabolism is influenced by several
      processes especially its dietary intake and the polymorphisms of the associated
      genes involved. Aberrant folate metabolism, therefore, affects both methylation
      as well as the DNA synthesis processes, both of which have been implicated in the
      development of various diseases. This paper reviews the current knowledge of the
      processes involved in folate metabolism and consequences of deviant folate
      metabolism, particular emphasis is given to the polymorphic genes which have been
      implicated in the development of various diseases in humans, like vascular
      diseases, Down's syndrome, neural tube defects, psychiatric disorders and
      cancers. 

PMID- 24091067
TI  - ["Factitious disorder and skin picking: Clinical approach". A case report].
AB  - OBJECTIVE: The number of patients requiring primary and secondary care for
      factitious disorder unexplained by any known medical condition is high. We report
      a case illustrating the clinical and psychopathological features of factitious
      disorder. The treatment difficulties encountered in the association of this
      disorder with dermatillomania are discussed. CASE REPORT: The patient was a 22
      year old girl with abrasions on the face and forearms with ingested epidermal
      layer of the skin. She also had multiple somatic complaints, the authenticity of
      which was difficult to confirm. The diagnosis of comorbid factitious disorder
      with dermatillomania was retained. In view of reducing self-harm acts, we
      prescribed a mood stabilizer associated with an anxiolytic for 6 months. The self
      harming acts have regressed, while the hypochondriacal complaints remain with a
      tendency of overstatement. DISCUSSION: Factitious disorder (FD) is a mental
      disorder occurring in patients acting intentionally similar to a physically or
      mentally sick person with no apparent benefits. The reported cases often show FD
      comorbidity with other psychiatric disorders such as substance abuse, somatoform
      disorders, dysthymia, borderline personality disorder and sexual disorders.
      Comorbidity of factitious disorder with neurotic excoriation is exceptional, and
      rarely described in the literature. Pathological skin picking (PSP) is a
      disabling disorder characterized by repetitive skin picking, which causes tissue
      damage. It was estimated to affect 2% of the population. PSP is currently listed
      as an impulse control disorder not otherwise specified, it is associated with a
      high rate of psychiatric comorbidity like borderline personality disorder.
      CONCLUSION: The comorbidity of factitious disorder and dermatillomania makes
      diagnosis very difficult. The limit between the two disorders is sometimes
      unclear.

PMID- 24091069
TI  - [Study of the psychometric properties of the CES-D in a sample of French-speaking
      adolescents].
AB  - The aim of this paper is to study and validate the French version of the Center
      for Epidemiologic Studies Depression Scale developed by Radloff (in 1977) in an
      adolescent sample. This scale was developed to measure levels of depressive
      symptomatology, with special emphasis on the affective components and depressed
      mood. METHOD: The data used in this study were collected in 11 schools. Our
      sample was composed of 1496 French-speaking, Belgian secondary school students
      aged 12 to 16 years. The questionnaire included demographic information such as
      age, gender, grade and family composition. The position of the CES-D scale has
      not changed and was placed in the last part of the self-administered
      questionnaire. RESULTS: After an exploratory factor analysis, we conducted
      confirmatory factor analysis to test our factor model. We tested the model with
      four factors proposed by Radloff (in 1977) and also the model proposed by Chabrol
      (in 2002). Our results indicate a better match with Radloff's model in our
      sample, showing the relevance of using Radloff's model with four factors in
      adolescents. Although our analysis shows a clear gender difference with regard to
      depressive symptoms, the tested factor model remained stable regardless of the
      gender of the adolescent.

PMID- 24091068
TI  - [Triggers of bulimia and compulsion attacks: validation of the "Start"
      questionnaire].
AB  - AIM: There are few published studies on the triggers of binge eating in anorexia
      nervosa of binge/purging subtype (BPAN), bulimia nervosa (BN) and binge eating
      disorder (BED). PATIENTS AND METHODS: We validated in 29 patients (10 BPAN, 10 BN
      and 9 BED) the perspicuity, the clarity and the intra- (doubles) and inter- (test
      retest) reproducibility of a 24-item Start questionnaire on the triggers of binge
      eating. Then the Start questionnaire was administered to 176 patients (65 BPAN,
      62 BN and 59 BED patients) being 27.5+9.1 yr old, having 15+9 binge eating (BE)
      episodes/week, with a mean binge duration of 1 hr 36min (+ 38min)/day. RESULTS:
      BE episodes occurred mainly during the second part of the day: afternoon after
      work (67% of the patients), "tea" time (55%), evening after dinner (42%) and at
      night (22%). The principal place for BE episodes was at home (96%). The BED
      patients avoided binges at the parents' home (89%) more often than the BPAN (62%,
      P<0.02). The binges occurred mainly in the living room (44%), in the kitchen
      (43%), and less in the bedroom (31%). Hunger pangs seemed to be a trigger of
      binges in 31% of the patients, and a stronger trigger in BED (42%) than in the
      BPAN and BN patients (24%; P=0.04). Binge eating episodes could occur despite a
      high satiety level (just after lunch or dinner) in 29% of the BN and in 16% of
      the BED patients (P<0.02). Concerning food, the major triggers were high energy
      density food (77%) and comfort food (60%), such as chocolate, cakes, bread and
      pasta. The food consumed for binge episodes (in-binge food) was more often a
      strong trigger than the other food (not used for binges): olfaction (19% versus
      10%), sight (52% versus 25%) and placing in the mouth (71% versus 26%; P<0.02 for
      all, in the 3 groups). Being tired could be a strong trigger in 37% of the
      patients, but "being aroused" in the other 38 % of the patients. Stressful events
      (65%), anxiety (74%), "being under pressure" or irritated (51% and 55%) were of
      course major triggers in a majority of the patients, as well as sadness (61%),
      feeling of powerlessness (62%), inefficiency (73%) and depressive state (71%).
      Flashback from traumatism (sexual trauma in 17% of the patients) was a strong
      trigger of binges more often in BPAN and BED (44%) than in BN (23%; P<0.05). The
      binge eating was painful (and "not at all a pleasure") in 69% of the patients,
      but could also be a relaxing behavior in 31% of the patients, more often in the
      BED (43%) than in the BPAN patients (20%; P<0.05). The binge eating behavior was
      quoted as obsessive in 63% of BPAN, 92% of BN and only 34% of BED patients
      (P<0.001). The patients said that they were unable to avoid the binge (76% of the
      patients), more often in BPAN and BN than in BED patients (P<0.01). As a whole,
      62% of BPAN, 89% of BN and only 4 % of BED patients (P<0.05) were unable to avoid
      purging (vomiting). In 12% of the cases, there was a pleasure felt when binging.
      For the other patients, shame, filth and incapacity were the feelings related to
      binges in 58% of the BPAN, 45% of BN and 43% of BED patients (P<0.04). The global
      score of addiction (zero=not addicted, 10=very addicted) was 8.56+1.2 in BPAN,
      8.42+1.5 in BN and 6.74+1.1 in BED patients (NS between BPAN and BN; P<0.01
      between BPAN and BN on the one hand and BED on the other). CONCLUSION: The
      present study has demonstrated the usefulness of the Start questionnaire. It also
      evidences the key role of intrinsic factors, both metabolic and emotional, as
      strong triggers for binge eating episodes in BPAN, BN and BED. It has also
      demonstrated the role of environmental determinants.

PMID- 24091070
TI  - [Health-related quality of life assessment in depression after low-frequency
      transcranial magnetic stimulation].
AB  - BACKGROUND: Major depressive disorder remains one of the leading causes of
      disability in developed countries despite pharmacological and psychological
      treatments. Patients with major depression have poorer health-related quality of
      life than persons of the general population, or patients with chronic somatic
      illness. Improvement of health-related quality of life in depression is thus a
      pertinent treatment objective. Both high-frequency repetitive transcranial
      magnetic stimulation (rTMS) over the left dorsolateral prefrontal cortex and low
      frequency rTMS over the right dorsolateral prefrontal cortex have shown their
      effectiveness in medication-resistant depression. However, the Health-related
      Quality of Life questionnaire remains under-utilized to assess the effectiveness
      of rTMS in research or in a routine clinical setting. Our study aims to
      investigate in an open label trial the efficacy of low-frequency rTMS over the
      right dorsolateral prefrontal cortex on health-related quality of life and
      clinical outcomes in medication-resistant depression. METHODS: In a naturalistic
      trial, 33 unipolar and bipolar patients with medication-resistant depression were
      treated with daily low-frequency rTMS over the right dorsolateral prefrontal
      cortex for 4 weeks. Health-related quality of life was assessed using the SF-36
      questionnaire. The SF-36 is a generic, self-administered, and worldwide-used
      questionnaire, consisting of 36 items describing eight health dimensions:
      physical functioning, social functioning, role-physical problems, role-emotional
      problems, mental health, vitality, bodily pain, and general health. Physical
      component summary and mental component summary scores were then obtained.
      Depression severity was assessed using the 21-item self-report Beck Depression
      Inventory. Anxiety severity was assessed using the State-Trait Anxiety Inventory.
      The SF-36, the Beck Depression Inventory and the State-Trait Anxiety Inventory
      were assessed before and after low-frequency rTMS. The effect of rTMS treatment
      on the SF-36 and the clinical outcome was evaluated for significance with the
      Wilcoxon two-tailed signed-rank test. The reliable change index (RCI) was
      calculated to determine clinically significant change in the eight dimension and
      composite scores of the SF-36 from pre-intervention to post-intervention, at the
      level of individual patients. Effect size (r) was then calculated, r values from
      0.1 to 0.29, 0.3 to 0.49 and from 0.5 were considered as indicating small, medium
      and large effect sizes, respectively. Correlations between improvement in Health
      related Quality of Life and improvement in the other rating scale scores were
      calculated using Spearman's correlation test. RESULTS: There were significant
      improvements of 37.6% in the mental health (P=0.018), 130 % in the role-emotional
      problem (P=0.045), 15.5% in the physical functioning (P=0.008), 110.6% in the
      role-physical problem (P=0.002), 22.4% in the bodily pain (P=0.013) dimensions,
      6.1% in the Physical Component Score (P=0.043), and 22,5 % in the Beck Depression
      Inventory (P=0.002). Eighteen patients (54%) showed clinically significant
      improvement in one of the two composite scores after RCI calculation. Seven out
      of the eight SF-36 dimension scores and the two composite scores showed effect
      sizes ranging from 0.12 to 0.38, indicating small to moderate effect. Significant
      correlations were found between improvement in the Beck Depression Inventory and
      improvement in the Mental Component Score, the social functioning, the mental
      health, the general health, the vitality and the physical functioning dimensions.
      LIMITATIONS: Small sample size and non-controlled design. CONCLUSION: Low
      frequency rTMS over the right dorsolateral prefrontal cortex improves Health
      related Quality of Life in unipolar and bipolar patients with medication
      resistant depression. Improvement in mental health-related quality of life is
      significantly correlated with improvement in depressive symptoms. However,
      further studies with larger samples and controlled designs are needed to clarify
      our findings.

PMID- 24091071
TI  - [Eating disorders and depressive symptoms: an epidemiological study in a male
      population].
AB  - OBJECTIVE: The objective of the study was to evaluate the incidence of eating
      disorders, including not otherwise specified eating disorders (EDNOS) and
      subthreshold disorders, inappropriate compensatory behaviors (such as self
      induced vomiting, strict dieting, fasting) along with depressive symptoms among
      young French adult males. METHOD: The sample was composed of 458 young men in age
      ranging from 18 to 30 years (mean age=21.9+/-2.4). The average body mass index
      was 22.8+/-3. Participants completed two questionnaires: the Questionnaire for
      Eating Disorders Diagnoses (Q-EDD) assessing full-criteria eating disorder
      symptoms based on DSM-IV criteria (i.e. clinical eating disorders) and
      subthreshold disorders, and the Center for Epidemiological Studies-Depression
      scale (CES-D) assessing depressive symptoms. RESULTS: Out of the 458 surveyed
      respondents, eating disorders were reported by approximately 17% of the overall
      sample, with 1.5% meeting diagnostic criteria for serious clinical disorders, 3%
      meeting diagnostic criteria for EDNOS and 12% meeting diagnostic criteria for
      subthreshold disorders. Exercise bulimia represented 1% of the overall sample and
      binge-eating disorder 2%. The most frequent subthreshold disorder was
      subthreshold nonbinging bulimia (7%). Participants with eating disorders were
      equally divided between those desiring weight gain, those desiring weight loss
      and those wanting to keep their current weight. Participants without eating
      disorders were more likely to want to gain weight compared to participants with
      eating disorders (45.5% versus 30% respectively; P<0.05). After controlling for
      body mass index, 30% of participants tended to perceive themselves as thinner
      than they actually were and 6% tended to perceive themselves as fatter. Regarding
      normal-weight participants, 28% perceived themselves as thinner and 8% as fatter
      than in reality. Overeating episodes were reported by 19% of participants. Binge
      eating episodes (recurrent or not) were reported by 8% of young men, including
      32% of participants with eating disorders and 3% of participants without eating
      disorder. Six percent reported repeated binging (at least twice a week for at
      least once a month). Inappropriate compensatory behaviors were mostly used by
      participants with eating disorders, except for excessive exercise (34% versus 35%
      for participants without eating disorders). The most typical compensatory
      behavior was fasting (11%). According to the cut-off score of 22, 18% of young
      men had a moderate to severe depressive symptomatology, including 5% of
      participants who also reported an eating disorder (i.e. 30 participants). A one
      way ANOVA was conducted to examine differences in depressive symptoms as a
      function of eating disorder groups, namely the clinical eating disorders sample
      (n=22), the subthreshold disorders sample (n=54) and the asymptomatic sample
      (participants without eating disorder; n=382). Results were statistically
      significant, (F(2,455)=7.27, P<0.001) and post-hoc tests (Scheffe tests) were
      used to examine the group differences. The mean CES-D scores for the clinical
      eating disorders sample (19.45+/-8.2; P<0.05) and the subthreshold disorders
      sample (18.15+/-10.9; P<0.05) were significantly higher than for the asymptomatic
      sample (14.19+/-8.9). There was no significant difference between the two eating
      disorder groups (P>0.05). DISCUSSION: The results demonstrate that a significant
      proportion of men with eating disorders manifest comorbid depressive
      symptomatology. These results suggest that EDNOS and subthreshold disorders
      should be taken into consideration, as they represent 15% of the total sample.
      Participants reported high rate of excessive exercise and fasting, which could
      reflect the importance of muscle tone or strategies to increase muscle mass.
      Further research is necessary in order to better understand male eating behaviors
      and disorders.

PMID- 24091072
TI  - Long-term patterns of use and treatment failure with anticholinergic agents for
      overactive bladder.
AB  - BACKGROUND: Overactive bladder (OAB) involves a complex set of symptoms with a
      lifetime prevalence of any symptom in ~30% of women and 20% of men.
      Anticholinergic agents are associated with poor medication persistence in OAB
      treatment. OBJECTIVE: This study evaluated the long-term patterns of use and
      treatment failure in patients prescribed anticholinergic agents for OAB. METHODS:
      This was a nonexperimental, retrospective cohort study. Medical, pharmacy, and
      eligibility data from the IMS LifeLink Health Plans Claims Database were used.
      Men and women aged >=18 years were eligible for inclusion with an International
      Classification of Diseases, Ninth Revision, Clinical Modification, diagnosis of
      OAB in any field during the patient study period from January 2005 to June 2010.
      First documentation of a prescription filled between July 2005 and June 2008 for
      an anticholinergic agent was defined as the index prescription. Other inclusion
      criteria were: >=1 pharmacy claim for an anticholinergic drug between July 2005
      and June 2008; continuous enrollment 6 months before the index date, during which
      no anticholinergic drugs were filled; and 24 months of follow-up from the index
      prescription. Study outcomes were treatment failure, discontinuation, switch,
      reinitiation, and adherence. Treatment failure was defined as having a treatment
      discontinuation (ie, treatment gap of >=45 days) or switching anticholinergic
      therapy. RESULTS: The analytic cohort comprised 103,250 patients with a mean age
      of 58.7 years. A majority were female (73%) and privately insured (75%). The vast
      majority of patients (91.7%) failed to meet their treatment goals with their
      index anticholinergic agent over the 24-month follow-up period. Of these, 5.8%
      switched, 51.3% permanently discontinued all anticholinergic agents, and 34.6%
      reinitiated treatment sometime after 45 days. The mean (SD) time to treatment
      failure was 159 (216.0) days, with a mean of 1.3 (0.5) unique anticholinergic
      agents per patient. Forty-eight percent of patients demonstrated appropriate
      adherence as determined by a medication possession ratio >=80%. CONCLUSIONS: This
      study provides real-world data on treatment patterns over 2 years in a large
      cohort of patients diagnosed with OAB. Despite the potential for better adherence
      with some anticholinergic agents, these analyses suggest that such benefits have
      not yet been realized, and many patients end up without effective
      pharmacotherapy. Thus, there is a need for new therapies and strategies to
      increase persistence and adherence to improve outcomes in OAB.

PMID- 24091073
TI  - Thyroid hormones-membrane interaction: reversible association of hormones with
      organized phospholipids with changes in fluidity and dipole potential.
AB  - Differential scanning calorimetry (DSC), mixed monomolecular layers and
      fluorescence spectroscopy techniques were applied to investigate the effect of
      thyroid hormones (THs) on the biophysical properties of model membranes. We found
      that both 3,3',5-triiodo-L-thyronine (T3) and 3,5,3',5'-tetraiodo-L-thyronine
      (T4) induce a broadening of the calorimetric main phase transition profile and
      reduce the transition enthalpy in liquid-crystalline state of
      dipalmitoylphosphatylcholine (DPPC) multilamellar vesicles. Tm changes from 41 
      degrees C to 40  degrees C compared to pure DPPC. When the experiments were done
      by adding THs to preformed multilamellar vesicles a second broader component in
      the DSC scan also appears at 20 min of incubation and becomes gradually more
      prominent with time, indicating a progressive alteration of lipid phase induced
      by THs. Analysis of surface pressure-molecular area isotherms in mixed monolayers
      of THs with either DPPC or 1-palmitoyl-2-oleoylphosphatidylcholine (POPC) at air
      water interface indicated a reduction in molecular area for THs/lipid mixtures at
      all surface pressures. A substantial decrease in surface potential in mixed
      lipid/THs monolayers at all surface pressures were observed for both
      phospholipids without affecting the mixed monolayer integrity. The data of mixed
      lipid/THs behavior support the establishment of lateral miscibility. Alterations
      of bidimensional liquid expanded->liquid condensed phase transition observed for
      DPPC/THs mixed monolayers are compatible with the changes observed in DSC. The
      transverse movement of THs and the decrease of dipole potential were also
      observed in single unilamellar vesicles by using appropriate fluorescent probes.

PMID- 24091074
TI  - Ovarian haemangioma: A rare case report.
AB  - INTRODUCTION: Haemangioma of ovary is a rare tumour. PRESENTATION OF CASE: We
      report an ovarian haemangioma which presented as an acute abdomen due to an
      adnexal mass. DISCUSSION: We report an ovarian haemangioma which presented as an
      acute abdomen due to an adnexal mass. Haemangiomas have been reported in other
      organs but ovarian haemangioma is a rare tumor, usually asymptomatic and
      presenting as an incidental finding. Large lesions tend to present clinically
      with pain. A few cases have been described in the literature. CONCLUSION:
      Considering their rare occurrence such tumors are a diagnostic challenge.

PMID- 24091075
TI  - Intra-abdominal pulmonary secuestration as an exceptional cause of abdominal mass
      in the adult.
AB  - INTRODUCTION: Pulmonary sequestration (PS) is an extremely rare malformation
      defined as a portion of lung tissue isolated from the pulmonary system. PSs are
      classified into intralobar type and intra-abdominal PS that represents only 2.5%
      of cases. There are 20 cases of PS reported in adults and only two were managed
      by laparoscopic approach. We report a case of intra-abdominal PS mimicking a
      gastroesophageal duplication cyst in an adult. Besides its rarity, this is the
      first intra-abdominal PS in an adult managed by an anterior laparoscopic
      approach. PRESENTATION OF CASE: A 60-year-old female patient had had epigastric
      and left upper quadrant pain for several days. Physical examination was normal.
      Image test were consistent with a gastroesophageal duplication. The patient was
      taken to the operating room for laparoscopic exploration and resection. The
      pathological diagnosis was extralobar pulmonary sequestration. DISCUSSION: Less
      than 20 cases of PS have been reported in adults and only two cases were managed
      by a lateral laparoscopic approach. In contrast to these reports, we used an
      anterior approach due to the GEJ suspected origin of the mass. CONCLUSION:
      Extralobar intra-abdominal PS is an extremely rare condition during adulthood but
      this diagnosis should be included in the differential diagnosis of a left-sided
      suprarenal mass. Due to the difficulty in achieving a definitive preoperative
      diagnosis, surgery is recommended. Laparoscopic resection is safe and effective
      but careful preoperative imaging studies are recommended in order to plan the
      most suitable approach.

PMID- 24091076
TI  - Uterine leiomyoma associated non-puerperal uterine inversion misdiagnosed as
      advanced cervical cancer: A case report.
AB  - INTRODUCTION: Uterine inversion is an un-common complication of parturition which
      often occurs in the immediate postpartum period. The chronic (non-puerperal)
      uterine inversion is rarer and most times tumour associated. PRESENTATION OF
      CASE: A 51-year old grand multiparous lady presented with a month history of
      abnormal vaginal bleeding associated with offensive vaginal discharge, lower
      abdominal pain and dizziness. The initial evaluation suggested severe anaemia
      secondary to advanced cervical cancer. Examination under anaesthesia (EUA),
      staging and biopsy was attempted but this was however inconclusive due to profuse
      haemorrhage. A repeat EUA revealed chronic uterine inversion secondary to fundal
      submucous uterine leiomyoma. Myomectomy was done with tissue histology confirming
      benign uterine leiomyoma. Two weeks later, a modified Haultain's procedure was
      done followed by simple hysterectomy and posterior colpoperineorrhaphy. She had
      satisfactory recovery. DISCUSSION: This is the first reported case of chronic non
      puerperal uterine inversion in our hospital. When it occurs, it is usually tumour
      associated with the commonest tumour being prolapsed myoma and leiomyosarcoma.
      The diagnosis is based on high index of suspicion. CONCLUSION: Chronic uterine
      inversion is a rare gynaecological condition and can be misdiagnosed as advanced
      cervical cancer or other causes of severe genital haemorrhage in women. A high
      index of suspicion is needed for its proper diagnosis. Sometimes, an EUA and
      biopsy was required to determine the cause here and conveniently it could be
      described as a "gynaecolological near miss".

PMID- 24091077
TI  - Prolene mesh migration into the rectum after sacral colpopexy presented with
      frozen pelvis.
AB  - INTRODUCTION: Pelvic organ prolapse (POP) is a common gynecological problem.
      Repair with synthetic materials such as prolene mesh has become a popular
      approach in prolapsus surgery. Migration of synthetic materials can cause serious
      complications. PRESENTATION OF CASE: A 69-year-old woman was admitted to the
      hospital with a complaint of sensation of fullness and a feeling of a foreign
      material protruding during defecation. The patient underwent exploratory
      laparotomy. Prolene mesh was detected in sacral region but resection of the mesh
      could not be conducted because of dense adhesions causing frozen pelvis. The
      migrated prolene mesh was resected transanally. DISCUSSION: Genital prolapse or
      genital hernia is described as the protrusion of pelvic organs along the vagina.
      It is one of the common gynecological conditions that affect the quality of life
      in women. Mesh migration is a well-known clinical pathology. CONCLUSION: Mesh
      migration is a serious complication after sacral colpopexy. Surgical resection of
      migrated mesh can be difficult due to dense adhesions.

PMID- 24091078
TI  - Successful treatment of triple primary tumor.
AB  - INTRODUCTION: The occurrence of multiple primary tumors is rare. Only limited
      number of cases with triple malignancy have been reported. We report here a rare
      case of a woman presented synchronous triple tumors, in her lung, breast, skin.
      PRESENTATION OF CASE: A 56-year-old woman presented with invasive ductal
      carcinoma of breast, non-small cell lung cancer and malignant melanoma. The
      patient undergone mastectomy and malignant melanoma tumor excision on-site. After
      operation stereotactic radiotherapy was given to her lung tumor. Six course of
      chemotherapy was given to her. She is alive with no progression. DISCUSSION: The
      patient was diagnosed with melanoma and staging by FDG/PET. There is not any
      study about routine using PET/CT in the melanoma staging. CONCLUSION: This is a
      very rare synchronous triple tumor case.

PMID- 24091079
TI  - Metabolomics in cancer biomarker discovery: current trends and future
      perspectives.
AB  - Cancer is one of the most devastating human diseases that causes a vast number of
      mortalities worldwide each year. Cancer research is one of the largest fields in
      the life sciences and despite many astounding breakthroughs and contributions
      over the past few decades, there is still a considerable amount to unveil on the
      function of cancer. It is well known that cancer metabolism differs from that of
      normal tissue and an important hypothesis published in the 1950s by Otto Warburg
      proposed that cancer cells rely on anaerobic metabolism as the source for energy,
      even under physiological oxygen levels. Following this, cancer central carbon
      metabolism has been researched extensively and beyond respiration, cancer has
      been found to involve a wide range of metabolic processes, and many more are
      still to be unveiled. Studying cancer through metabolomics could reveal new
      biomarkers for cancer that could be useful for its future prognosis, diagnosis
      and therapy. Metabolomics is becoming an increasingly popular tool in the life
      sciences since it is a relatively fast and accurate technique that can be applied
      with either a particular focus or in a global manner to reveal new knowledge
      about biological systems. There have been many examples of its application to
      reveal potential biomarkers in different cancers that have employed a range of
      different analytical platforms. In this review, approaches in metabolomics that
      have been employed in cancer biomarker discovery are discussed and some of the
      most noteworthy research in the field is highlighted. 

PMID- 24091080
TI  - Synthesis, docking, and biological studies of phenanthrene beta-diketo acids as
      novel HIV-1 integrase inhibitors.
AB  - In the present study we report the synthesis of halogen-substituted phenanthrene
      beta-diketo acids as new HIV-1 integrase inhibitors. The target phenanthrenes
      were obtained using both standard thermal- and microwave-assisted synthesis. 4-(6
      Chlorophenanthren-2-yl)-2,4-dioxobutanoic acid (18) was the most active compound
      of the series, inhibiting both 3'-end processing (3'-P) and strand transfer (ST)
      with IC50 values of 5 and 1.3 MUM, respectively. Docking studies revealed two
      predominant binding modes that were distinct from the binding modes of
      raltegravir and elvitegravir, and suggest a novel binding region in the IN active
      site. Moreover, these compounds are predicted not to interact significantly with
      some of the key amino acids (Q148 and N155) implicated in viral resistance.
      Therefore, this series of compounds can further be investigated for a possible
      chemotype to circumvent resistance to clinical HIV-1 IN inhibitors.

PMID- 24091081
TI  - Discovery of pyrazolo[1,5-a]pyrimidine-based Pim inhibitors: a template-based
      approach.
AB  - The synthesis and hit-to-lead SAR development from a pyrazolo[1,5-a]pyrimidine
      derived hit 5 to the identification of a series of potent, pan-Pim inhibitors
      such as 11j are described. 

PMID- 24091083
TI  - Serum matrix metalloproteinase-9 and tissue inhibitor of metalloproteinase-1
      levels in patients with tick-borne encephalitis.
AB  - OBJECTIVES: Matrix metalloproteinase-9 (MMP-9) and tissue inhibitor of
      metalloproteinase-1 (TIMP-1) play important roles in the function of the blood
      brain barrier (BBB). To investigate the function of the BBB during tick-borne
      encephalitis (TBE), the levels of MMP-9 and its common tissue inhibitor, TIMP-1,
      were measured in serum from patients with acute phase of TBE. METHODS: Serum MMP
      9 and TIMP-1 levels were measured in 147 patients with TBE and 153 controls by
      ELISA. RESULTS: Serum MMP-9 levels and MMP-9/TIMP-1 ratios of TBE patients were
      significantly higher than controls (p < 0.0001 and p < 0.005, respectively).
      There were no significant differences in serum TIMP-1 levels between TBE patients
      and controls. Serum MMP-9 and TIMP-1 levels and MMP-9/TIMP-1 ratios were not
      associated with age of the patients. However, TBE-positive males with TBE had
      higher levels of MMP-9 than TBE-positive females (p < 0.05). CONCLUSIONS: Our
      results suggest that the increased serum level of MMP-9 and MMP-9/TIMP-1 ratio is
      associated with the pathogenesis of TBE. Serum MMP-9 can serve as an indicator of
      breakdown of the BBB and inflammatory brain damage during TBE.

PMID- 24091082
TI  - Difficulties with diagnosis and consequential poor outcome due to stigma of
      acquired immunodeficiency syndrome - a case report.
AB  - Low incidence of human immunodeficiency virus (HIV) infections and acquired
      immunodeficiency syndrome (AIDS) has been detected in Croatia so far. Toxoplasmic
      encephalitis (TE) is the most common opportunistic cerebral infection in AIDS
      patients and is highly responsive to antiparasitic chemotherapy, if treated at an
      early stage. We present the case of the brain biopsy confirmed as TE on a 36-year
      old female patient who at admission presented with unconsciousness and a right
      hemiplegia. A MSCT was performed and two hypodense lesions were diagnosed. The
      patient's family initially denied the presence or history of any medical problem
      or infection. An MRI showed multiple ring-enhanced mass lesions. An infectologist
      required a brain biopsy to exclude cerebral lymphoma and multiple metastases.
      Pathohistological analysis suggested TE. Meanwhile, patient's blood samples were
      found to be HIV positive. The patient was transferred to University Hospital for
      Infectious Diseases in Zagreb, where she died 2 days following admission. The
      patient's family terminally confessed that the patient had been HIV positive for
      10 years and had refused any treatment. Family's denial of infection as well as
      'hiding information' concerning patient's health from physicians involved in her
      treatment caused a delay in proper on-time patient treatment. We would like to
      emphasize that TE must be considered as a differential diagnosis in patients
      presenting with multiple cerebral lesions, including patients without
      acknowledged past history of HIV infection. A stigma towards HIV infection and
      ignorance of the disease still exist and therefore hinders proper treatment. 

PMID- 24091084
TI  - A giant right coronary artery related to a small fistula to the coronary sinus.
AB  - Coronary artery fistulas to the coronary sinus are very rare coronary anomalies
      most often resulting in extreme dilatation of the donor coronary artery and the
      receiving vessel. However, despite common impressive appearance, their clinical
      and functional impact may be extremely various from asymptomatic and benign cases
      to disabling and life threatening situations. To adequately stratify the inherent
      risks and to plan the most appropriate therapeutic strategy, an overall
      investigation is necessary. We herein report the case of a 56year-old woman with
      a giant right coronary artery related to a small and restrictive fistula to the
      coronary sinus that was extensively investigated by multi-imaging strategy before
      decision of a therapeutic abstention and long-term follow-up. 

PMID- 24091085
TI  - Do we really need ribavirin in the treatment of crimean-congo hemorrhagic Fever?
AB  - The role of ribavirin in the treatment of Crimean-Congo hemorrhagic fever (CCHF)
      is scarce. We retrospectively reviewed treatment features of 81 hospitalized
      patients with laboratory confirmed CCHF between January 2007 and December 2010.
      The median age of the patients was 45 years and 47 were male. Out of 81 patients,
      6 received ribavirin. Demographic characteristics and laboratory findings of the
      patients who received ribavirin were not different from the patients who did not
      receive antiviral. There were no statistically significant difference in duration
      of symptoms before admission (P = 0.47) between the two groups. Of the patients,
      29 who did not receive ribavirin and four from the ribavirin treated group had
      severe disease based on the Swanpoel criteria (P = 0.22). Two patients from each
      group died. There was no statistically significant difference in case fatality (P
      = 0.14) and duration of hospitalization (P = 0.11). Treatment of CCHF without
      ribavirin seems to be safe based on the findings of this study. 

PMID- 24091086
TI  - Extensive cutaneous necrosis in a 12-year-old girl: an unusual complication of
      secondary cold agglutinin syndrome.
AB  - Cold agglutinin syndrome (CAS) secondary to infection is rare, usually presenting
      with anaemia and minor skin changes. A 12-year-old girl with secondary CAS
      associated with extensive cutaneous necrosis is reported. She presented with
      fever and multiple necrotic lesions over both cheeks, the tip of nose, ear
      margins, hands and buttocks, along with pallor, hepatospenomegaly, acrocyanosis
      and gangrene of the fifth digit of the right hand. She had anaemia, unconjugated
      hyperbilirubinaemia and a positive direct antiglobulin test owing to cold
      agglutinins of the IgM type with anti-i specificity and titres of 1:512 at 4
      degrees C. Results of bone marrow examination were normal and cryoglobulins were
      negative. Cold antibodies released even during a brief, self-limited febrile
      illness can cause widespread cutaneous gangrene. We believe this is the first
      report in the paediatric age group.

PMID- 24091087
TI  - Age-specific and sex-specific morbidity and mortality from avian influenza
      A(H7N9).
AB  - We used data on age and sex for 136 laboratory confirmed human A(H7N9) cases
      reported as of 11 August 2013 to compare age-specific and sex-specific patterns
      of morbidity and mortality from the avian influenza A(H7N9) virus with those of
      the avian influenza A(H5N1) virus. Human A(H7N9) cases exhibit high degrees of
      age and sex bias: mortality is heavily biased toward males >50 years, no deaths
      have been reported among individuals <25 years old, and relatively few cases
      documented among children or adolescents. The proportion of fatal cases (PFC) for
      human A(H7N9) cases as of 11 August 2013 was 32%, compared to a cumulative PFC
      for A(H5N1) of 83% in Indonesia and 36% in Egypt. Approximately 75% of cases of
      all A(H7N9) cases occurred among individuals >45 years old. Morbidity and
      mortality from A(H7N9) are lowest among individuals between 10 and 29 years, the
      age group which exhibits the highest cumulative morbidity and case fatality rates
      from A(H5N1). Although individuals <20 years old comprise nearly 50% of all human
      A(H5N1) cases, only 7% of all reported A(H7N9) cases and no deaths have been
      reported among individuals in this age group. Only 4% of A(H7N9) cases occurred
      among children<5 years old, and only one case from the 10 to 20 year age group.
      Age- and sex-related differences in morbidity and mortality from emerging
      zoonotic diseases can provide insights into ecological, economic, and cultural
      factors that may contribute to the emergence and proliferation of novel zoonotic
      diseases in human populations. 

PMID- 24091088
TI  - The relationship between usage intention and adoption of electronic health
      records at primary care clinics.
AB  - OBJECTIVE: Despite of emerging evidence that electronic health records (EHRs) can
      improve the clinical quality, enhances patient safety and efficiency. Most
      physicians in primary health care clinics in the Taiwan do not currently adopt
      EHR at their clinic practices. We aim to measure the relationship between usage
      intention and adoption behavior. STUDY DESIGN AND METHODS: We used structured
      questionnaires distributed both EHRs adopter and non-adopter group to the primary
      health care physicians which participated in the DOH project to establish the
      information exchange environment across Taiwan. The response rate of adopter and
      non-adopter is 54.7% and 55.0% respectively. MEASUREMENTS: EHRs adoption
      behavior. RESULTS: The EHRs adopter group has higher intention than non-adopter
      (p=0.003). From the result of logistic regression analyses, we found the key
      factors affecting physicians' adoption pattern were intention to use (OR: 2.85;
      95% CI: 2.30-3.54). In addition, higher perceived usefulness (OR: 1.29; 95% CI:
      1.06-1.56) and perceived ease to use (OR: 1.48; 95% CI: 1.22-1.79) increase
      adoption of EHR found. CONCLUSION: The intention to use EHR, perceived usefulness
      and ease to use of primary care physicians were found as key factors influencing
      EHRs adoption. Thus, we suggest that government should promote the potential
      benefits of EHR and enhance physicians' willingness to adopt the EHRs at their
      clinic practices.

PMID- 24091090
TI  - Chromatin dynamics during spermiogenesis.
AB  - The function of sperm is to safely transport the haploid paternal genome to the
      egg containing the maternal genome. The subsequent fertilization leads to
      transmission of a new unique diploid genome to the next generation. Before the
      sperm can set out on its adventurous journey, remarkable arrangements need to be
      made during the post-meiotic stages of spermatogenesis. Haploid spermatids
      undergo extensive morphological changes, including a striking reorganization and
      compaction of their chromatin. Thereby, the nucleosomal, histone-based structure
      is nearly completely substituted by a protamine-based structure. This replacement
      is likely facilitated by incorporation of histone variants, post-translational
      histone modifications, chromatin-remodeling complexes, as well as transient DNA
      strand breaks. The consequences of mutations have revealed that a protamine-based
      chromatin is essential for fertility in mice but not in Drosophila. Nevertheless,
      loss of protamines in Drosophila increases the sensitivity to X-rays and thus
      supports the hypothesis that protamines are necessary to protect the paternal
      genome. Pharmaceutical approaches have provided the first mechanistic insights
      and have shown that hyperacetylation of histones just before their displacement
      is vital for progress in chromatin reorganization but is clearly not the sole
      inducer. In this review, we highlight the current knowledge on post-meiotic
      chromatin reorganization and reveal for the first time intriguing parallels in
      this process in Drosophila and mammals. We conclude with a model that illustrates
      the possible mechanisms that lead from a histone-based chromatin to a mainly
      protamine-based structure during spermatid differentiation. This article is part
      of a Special Issue entitled: Chromatin and epigenetic regulation of animal
      development. 

PMID- 24091091
TI  - Long-term renal outcomes of consecutive patients undergoing open type IV
      thoracoabdominal aneurysm repair.
AB  - OBJECTIVE: To evaluate long-term renal outcomes after open type IV
      thoracoabdominal aneurysm (TAAA) repair. DESIGN: Retrospective analysis of a
      prospectively collected database of consecutive operated non-ruptured type IV
      TAAAs (2007-2011). METHODS: Renal function was analysed by serum creatinine
      concentration, estimated glomerular filtration rate (eGFR) and Kidney Disease
      Outcomes Quality Initiative (KDOQI) stage. The primary outcome was the change in
      creatinine concentration from before surgery to defined time points after
      surgery: peak postoperative; discharge; at follow-up (>1 year postoperatively).
      Secondary outcomes were change in eGFR, change in KDOQI stage, dialysis
      requirement, and 30-day mortality. RESULTS: Between 2007 and 2011, 53 open type
      IV TAAA repairs were performed. Median creatinine levels significantly increased
      in the immediate postoperative period, but returned to baseline by discharge.
      Thirteen patients (28.2%) had an improvement in follow-up eGFR of at least 20%
      compared with pre-operative eGFR or improved by one KDOQI stage. Twelve patients
      (26.1%) had a decline in eGFR of at least 20% or one KDOQI stage at follow-up.
      Three patients (7.5%) required temporary dialysis and one patient (1.9%) required
      permanent dialysis. The 30-day mortality was 1.9%. CONCLUSIONS: This study
      demonstrates acceptable renal outcomes following open type IV TAAA repair. Open
      type IV repair remains the standard against which newer techniques should be
      compared.

PMID- 24091089
TI  - Brain microstructural development at near-term age in very-low-birth-weight
      preterm infants: an atlas-based diffusion imaging study.
AB  - At near-term age the brain undergoes rapid growth and development. Abnormalities
      identified during this period have been recognized as potential predictors of
      neurodevelopment in children born preterm. This study used diffusion tensor
      imaging (DTI) to examine white matter (WM) microstructure in very-low-birth
      weight (VLBW) preterm infants to better understand regional WM developmental
      trajectories at near-term age. DTI scans were analyzed in a cross-sectional
      sample of 45 VLBW preterm infants (BW<=1500g, GA<=32weeks) within a cohort of 102
      neonates admitted to the NICU and recruited to participate prior to standard-of
      care MRI, from 2010 to 2011, 66/102 also had DTI. For inclusion in this analysis,
      45 infants had DTI, no evidence of brain abnormality on MRI, and were scanned at
      PMA <=40weeks (34.7-38.6). White matter microstructure was analyzed in 19
      subcortical regions defined by DiffeoMap neonatal brain atlas, using threshold
      values of trace <0.006mm(2)s(-1) and FA >0.15. Regional fractional anisotropy
      (FA), mean diffusivity (MD), axial diffusivity (AD), and radial diffusivity (RD)
      were calculated and temporal-spatial trajectories of development were examined in
      relation to PMA and brain region location. Posterior regions within the corona
      radiata (CR), corpus callosum (CC), and internal capsule (IC) demonstrated
      significantly higher mean FA values compared to anterior regions. Posterior
      regions of the CR and IC demonstrated significantly lower RD values compared to
      anterior regions. Centrally located projection fibers demonstrated higher mean FA
      and lower RD values than peripheral regions including the posterior limb of the
      internal capsule (PLIC), cerebral peduncle, retrolenticular part of the IC,
      posterior thalamic radiation, and sagittal stratum. Centrally located association
      fibers of the external capsule had higher FA and lower RD than the more
      peripherally-located superior longitudinal fasciculus (SLF). A significant
      relationship between PMA-at-scan and FA, MD, and RD was demonstrated by a
      majority of regions, the strongest correlations were observed in the anterior
      limb of the internal capsule, a region undergoing early stages of myelination at
      near-term age, in which FA increased (r=.433, p=.003) and MD (r=-.545, p=.000)
      and RD (r=-.540, p=.000) decreased with PMA-at-scan. No correlation with PMA-at
      scan was observed in the CC or SLF, regions that myelinate later in infancy.
      Regional patterns of higher FA and lower RD were observed at this near-term age,
      suggestive of more advanced microstructural development in posterior compared to
      anterior regions within the CR, CC, and IC and in central compared to peripheral
      WM structures. Evidence of region-specific rates of microstructural development
      was observed. Temporal-spatial patterns of WM microstructure development at near
      term age have important implications for interpretation of near-term DTI and for
      identification of aberrations in typical developmental trajectories that may
      signal future impairment. 

PMID- 24091092
TI  - Three-dimensional ultrasound improves the accuracy of diameter measurement of the
      residual sac in EVAR patients.
AB  - OBJECTIVES: Discrepancy between maximum diameters obtained with two-dimensional
      ultrasound and computed tomography (CT) after endovascular aneurysm repair (EVAR)
      is well known. The maximal diameter is ideally measured perpendicular to the
      centerline, a methodology so far only feasible with three-dimensional (3D) CT and
      magnetic resonance angiography (MRA). We aimed to investigate the agreement
      between 3D ultrasound and 3D CT and to determine reproducibility measures.
      METHODS: Prospective study comparing 3D ultrasound with 3D CT in 124 consecutive
      patients seen 3 or 12 month after EVAR. RESULTS: Replacing 2D with 3D ultrasound,
      the mean difference was improved from 6.0 mm to -1.3 mm (p < .001), and the range
      of variability was reduced from 9.4 mm to 6.6 mm (p = .009) using 3D CT as the
      gold standard. The mean difference between 3D ultrasound and 3D CT maximum
      diameter of the residual sac was -1.3 mm with upper and lower limits of agreement
      of 5.2 mm and -7.9 mm, respectively. Reproducibility measures of 3D ultrasound
      were +/- 4 mm. CONCLUSION: 3D ultrasound correlate significantly better to 3D CT
      than the currently used 2D ultrasound method when assessing maximum diameter of
      the residual sac after EVAR, and reproducibility measures were within clinical
      acceptable values.

PMID- 24091093
TI  - Calcification as a risk factor for rupture of abdominal aortic aneurysm.
AB  - OBJECTIVES: Abdominal aortic aneurysm (AAA) is a major cause of death in
      developed countries. The AAA diameter is still the only validated prognostic
      measure for rupture, and therapeutic interventions are initiated accordingly.
      This still leads to unnecessary interventions in some cases or unidentified
      impending ruptures. Vascular calcification has been validated abundantly as a
      risk factor in the cardiovascular field and may strengthen the rupture risk
      assessment of the AAA. With this study we aim to assess the correlation between
      AAA calcification and rupture risk in a retrospective unmatched case-control
      population. METHODS: A database of 334 AAA patients was evaluated. Three groups
      were formed: elective (eAAA; n = 233), ruptured (rAAA; n = 73) and symptomatic
      non-ruptured (sAAA; n = 28) AAA patients. The Abdominal Aortic Calcification-8
      score (AAC-8) was used to measure the severity of vascular calcification.
      RESULTS: The AAA diameter (61 +/- 12 mm vs. 74 +/- 21 mm; p < .001) and AAC-8
      score (3.4 +/- 2 points vs. 4.9 +/- 2.3 points; p < .001) of the eAAA and the
      combined rAAA and sAAA groups, respectively, were significantly different after
      univariate analysis. Multivariate analysis showed that larger AAA diameter (odds
      ratio [OR]: 1.048/mm increase; 95% confidence interval [CI]: 1.042-1.082; p <
      .001) and a higher AAC-8 score (OR: 1.34/point increase; 95% CI: 1.19-1.53; p <
      .001) were significantly associated with development into a sAAA or rAAA.
      Peripheral artery disease was significantly correlated to eventual elective
      treatment (OR: 0.39; 95% CI: .15-1; p = .049). CONCLUSION: This study suggests a
      trend of an increased degree of calcification in symptomatic or even ruptured AAA
      patients compared with elective AAA patients.

PMID- 24091094
TI  - Results from craniocaudal carotid body tumor resection: should it be the standard
      surgical approach?
AB  - OBJECTIVES: To evaluate results after carotid body tumor (CBT) surgery using a
      novel dissection technique. METHODS: A retrospective analysis of all operated CBT
      in the last 6 years was carried out and results were compared with the current
      literature and our previous series, which reported another 111 cases operated on
      until 2005. RESULTS: Forty-five CBTs were removed in 41 (56% hereditary cases)
      patients (seven Shamblin I, 22 II, and 16 III). There were no cases of permanent
      cranial nerve injury or stroke. These pre- and postoperative results compare
      favorably with our previous series and are superior to, generally smaller,
      studies reported in the contemporary literature. CONCLUSIONS: This large series
      of surgically-treated CBTs supports craniocaudal dissection as the surgical
      technique of choice as it limits blood loss and facilitates safe CBT resection.

PMID- 24091095
TI  - Incompleteness of the circle of Willis is related to EEG-based shunting during
      carotid endarterectomy.
AB  - OBJECTIVES: The occurrence of cerebral ischemia during carotid endarterectomy
      (CEA) can be prevented by (selective) placement of an intraluminal shunt during
      cross-clamping. We set out to develop a rule to predict the likelihood for
      shunting during CEA based on preoperative assessment of collateral cerebral
      circulation and patient characteristics. METHODS: Patients who underwent CEA
      between 2004 and 2010 were included. Patients without preoperative magnetic
      resonance (MRA) or computed tomography angiography (CTA) were excluded. The
      primary endpoint was intraluminal shunt placement based on electroencephalography
      changes. Age, sex, cardiovascular risk factors peripheral artery disease,
      symptomatic status, degree of ipsilateral and contralateral carotid, status of
      the vertebral arteries, and morphology of the CoW were studied as potential
      predictors for shunt use. A prediction model was derived from a multivariable
      regression model using discrimination, calibration, and bootstrapping approaches
      and transformed into a clinical prediction model. RESULTS: A total of 431
      patients were included, of which 65 patients (15%) received an intraluminal
      shunt. In the MRA group (n = 285) factors related to shunt use in multivariate
      analysis were ipsilateral carotid stenosis 90-99% (odds ratio [OR] 0.15, 95% CI
      0.04-0.53), contralateral carotid occlusion (OR 4.29, 95% CI 1.68-10.95) and any
      not-visible anterior (OR 4.96, 95% CI 1.95-12.58) or ipsilateral posterior
      segment of the CoW (OR 5.08, 95% CI 2.10-12.32). In the CT group none of the
      factors were independently related to shunt use; therefore, only predictors
      describing morphology of CoW derived from MRA findings were included in our
      model. The c-statistic of this model was 0.79 (95% CI 0.72-0.86). Among patients
      with an estimated chance of needing a shunt of under 10% (49% of the population),
      the likelihood of shunting was 5%. In those in whom this chance was estimated
      higher than 30% (13% of the population) the likelihood was 51%. CONCLUSIONS:
      Among patients scheduled for CEA, assessment of cerebral arteries and of the
      configuration of the CoW based on MRA-derived images can help to identify
      patients with low and high likelihood of the need of shunt use during surgery.

PMID- 24091096
TI  - The shortfall in long-term survival of patients with repaired thoracic or
      abdominal aortic aneurysms: retrospective case-control analysis of hospital
      episode statistics.
AB  - OBJECTIVE: To report the contemporary life expectancy of patients undergoing
      abdominal (AAA) or thoracic aortic aneurysm (TAA) repair in England, relative to
      a healthy control population. METHODS: A retrospective observational case-control
      study was carried out of Hospital Episode Statistics (HES) data, an
      administrative dataset covering the entire English National Health Service.
      Patients undergoing elective repair of an abdominal or thoracic aortic aneurysm
      in an English NHS hospital between April 2006 and March 2011 were included.
      Outcome measures were 5-year all-cause mortality (in- and out-of-hospital) and
      adverse cardiovascular events (myocardial infarction, stroke, emergency
      amputation or limb revascularisation). RESULTS: 19,505 AAA and 730 TAA repairs
      were identified, with 75,260 and 2,721 control participants, respectively, and
      27.5 (1.0-60.0) months' median (range) follow-up. Five-year survival was 67.4%
      for AAA against 81.1% for control participants, and 65.3% for TAA against 89.1%
      for control participants (p < .001). Freedom from adverse cardiovascular events
      was 86.1% for AAA against 93% for control participants and 89.1% for TAA against
      94.4% for control participants (p < .001). CONCLUSION: Long-term survival remains
      poor after aneurysm repair and adverse cardiovascular events are common relative
      to the wider population. Further research is required to characterise and
      optimise cardiovascular risk prevention in patients with aortic aneurysms.

PMID- 24091097
TI  - Biological variation of free light chains in serum.

PMID- 24091098
TI  - Laboratory formularies.
AB  - Clinical laboratories face increasing costs along with increased expectation to
      ensure appropriate use of diagnostic tests by physicians. One administrative
      mechanism that has been used successfully for this purpose is the laboratory
      formulary. Modeled after drug formularies, this is simply a list of diagnostic
      tests approved for use in a particular setting, possibly including additional
      restrictions regarding who may order a particular test and under what
      circumstances. This brief review summarizes the principles underlying laboratory
      formularies and suggests strategies for using them effectively. 

PMID- 24091099
TI  - Utilization management in toxicology.
AB  - Recent upward trends in the prevalence of abuse of prescription drugs and illicit
      substances have resulted in increased demands for toxicology testing to support
      the emergency department and drug treatment in pain management programs. This
      review will discuss the challenges faced by clinical laboratories to manage the
      utilization of toxicology tests, particularly those ordered in managing poisoned
      patients in the emergency department and chronic pain patients on opioid therapy.
      Optimal utilization of toxicology tests to support the emergency department
      relies on selecting the appropriate tests for the patient, and the availability
      of the results in a timely fashion. Two tiers of toxicology testing systems with
      different requirements for turnaround time will be discussed. In patients with
      chronic pain urine drug testing, including screening and confirmation testing are
      used extensively in pain management to monitor patient compliance. A thorough
      understanding of the performance characteristics of the test methodologies and
      drug metabolism is a key to making a proper analytical and clinical
      interpretation of the test results and will contribute to effective utilization
      of these tests. In addition, the reimbursement system is an important factor in
      the decision making process for test selection utilization as significant costs
      can be incurred by both payers and patients. Collaboration, trust, and effective
      communication among clinicians, patients, and clinical laboratory professionals
      are essential for effective utilization of toxicology testing. 

PMID- 24091100
TI  - Chemotherapy-related toxicity in patients with non-metastatic Ewing sarcoma:
      influence of sex and age.
AB  - Influence of age and sex on chemotherapy-related toxicity was evaluated in
      children (3-9 years), adolescents (10-17 years), and adults (up to 40 years) with
      localized Ewing sarcoma (ES) enrolled in the ISG/SSG III protocol. Treatment was
      based on vincristine, doxorubicin, cyclophosphamide, ifosfamide, dactinomycin,
      and etoposide. High-dose chemotherapy with busulfan and melphalan was given in
      poor responder patients. The analysis was based on 2191 courses of standard
      chemotherapy and 230 patients. A lower risk of G4 leukopenia and
      thrombocytopenia, hospitalization, febrile neutropenia, and red blood cell (RBC)
      transfusions was observed in males. Use of granulocyte colony-stimulating factor
      (G-CSF) was more frequent in adults, while children more often received RBC
      transfusions. A significant correlation between sex and chemotherapy-related
      toxicity was observed in the study, whereas no significant differences in terms
      of bone marrow toxicity can be expected according to patient age. Further studies
      should analyse the role of pharmacokinetics, pharmacogenomics, and clinical
      characteristics. 

PMID- 24091101
TI  - SHIP2 signaling in normal and pathological situations: Its impact on cell
      proliferation.
AB  - Phosphoinositide 5-phosphatases are critical enzymes in modulating the
      concentrations of PI(3,4,5)P3, PI(4,5)P2 and PI(3,5)P2. The SH2 domain containing
      inositol 5-phosphatases SHIP1 and SHIP2 belong to this family of enzymes that
      dephosphorylate the 5 position of PI(3,4,5)P3 to produce PI(3,4)P2. Data obtained
      in zebrafish and in mice have shown that SHIP2 is critical in development and
      growth. Exome sequencing identifies mutations in the coding region of SHIP2 as a
      cause of opsismodysplasia, a severe but rare chondrodysplasia in human. SHIP2 has
      been reported to have both protumorigenic and tumor suppressor function in human
      cancer very much depending on the cell model. This could be linked to the
      relative importance of PI(3,4)P2 (a product of SHIP2 phosphatase activity) which
      is also controlled by the PI 4-phosphatase and tumor suppressor INPP4B. In the
      glioblastoma cell line 1321 N1, that do not express PTEN, lowering SHIP2
      expression has an impact on the levels of PI(3,4,5)P3, cell morphology and cell
      proliferation. It positively stimulates cell proliferation by decreasing the
      expression of key regulatory proteins of the cell cycle such as p27. Together the
      data point out to a role of SHIP2 in development in normal cells and at least in
      cell proliferation in some cancer derived cells. 

PMID- 24091102
TI  - Accelerated myelination along fiber tracts in patients with hemimegalencephaly.
AB  - BACKGROUND AND PURPOSE: In infants with hemimegalencephaly, asymmetrical white
      matter intensities suggestive of advanced myelination are observed as well as
      aberrant midsagittal fibers (AMFs) specific to hemimegalencephaly. Also noted are
      otherwise unreported abnormally enlarged periventricular fibers (APVFs) running
      anteroposteriorly along the caudate nucleus. This study investigated the degree
      of myelination and presence of aberrant fibers in hemimegalencephaly through a
      retrospective review of MRI scans in relation to histopathological findings.
      MATERIALS AND METHODS: MRI scans of 24 infants with hemimegalencephaly (13 boys
      and 11 girls, 1-9 months old) were evaluated, focusing on the presence and signal
      intensities of AMFs and APVFs. White-matter signal intensities on T1- and T2
      weighted imaging of the cerebral hemisphere were also evaluated and compared with
      the timetable for normal myelination. Surgical specimens were pathologically
      examined with Kluver-Barrera staining in four patients. RESULTS: AMFs and APVFs
      were observed in 18 and nine patients, respectively, while 22 patients had
      accelerated myelination of the megalencephalic hemisphere that tended to extend
      along fiber pathways including AMFs and APVFs. In six cases, accelerated
      myelination even extended into the contralateral hemisphere via the corpus
      callosum or AMFs. Histopathological analysis identified hypermyelination with
      disarrayed myelinated fibers corresponding to MRI findings. CONCLUSION:
      Accelerated myelination is frequently observed in patients with
      hemimegalencephaly and tends to extend along fiber pathways, including aberrant
      or abnormal fibers, as seen in 75% of hemimegalencephaly patients. Accelerated
      myelination may reflect propagation pathways of abnormal brain activity in such
      patients.

PMID- 24091104
TI  - Comparative evaluation of a novel chromogenic medium (chromID OXA-48) for
      detection of OXA-48 producing Enterobacteriaceae.
AB  - Comparative evaluation of the recently developed chromogenic culture medium
      chromID OXA-48 (bioMerieux) with chromID CARBA (bioMerieux) and SUPERCARBA showed
      that chromID OXA-48 and SUPERCARBA media have the highest sensitivity for
      detection of OXA-48 producing Enterobacteriaceae (91% and 93%) comparatively to
      chromID CARBA (21 %). The chromID OXA-48 has the highest specificity, with 100%,
      as compared to 53% and 68% for the SUPERCARBA and chromID CARBA media for
      detecting those OXA-48 producers. 

PMID- 24091105
TI  - Multicenter research on the BACTEC MGIT 960 system for the second-line drugs
      susceptibility testing of Mycobacterium tuberculosis in China.
AB  - The reliability of the BACTEC MGIT 960 system for the second-line drugs
      (capreomycin [CPM], kanamycin [KAN], ofloxacin [OFX] and ethionamide [ETH])
      susceptibility testing (DST) of Mycobacterium tuberculosis (M. tuberculosis) was
      compared to that of traditional Lowenstein-Jensen (L-J) proportion method (PM)
      among four different sites in China. After resolution of discrepant results by
      retesting the strains using both methods in the National Reference Laboratory of
      tuberculosis, the overall concordance values between the 2 systems were 99.7%
      (kappa value: 0.97) for CPM, 99.7% (kappa value: 0.97) for KAN, 100.0% (kappa
      value: 1.00) for OFX, and 98.6% (kappa value: 0.95) for ETH. The average
      turnaround time with BACTEC MGIT 960 system among four sites was 8.9 +/- 1.7
      days, significantly shorter than 28 days with the traditional L-J PM. Therefore,
      the BACTEC MGIT 960 system is a reliable and rapid method for the second-line
      drug susceptibility testing of tuberculosis in China. Notably, a stricter quality
      control program should be routinely carried out when clinical laboratories
      perform the second-line DST with BACTEC MGIT 960 system. 

PMID- 24091106
TI  - Cefazolin as a class representative for oral cephalosporins and uncomplicated
      urinary tract infections caused by indicated Enterobacteriaceae.

PMID- 24091103
TI  - Non-phenotypic tests to detect and characterize antibiotic resistance mechanisms
      in Enterobacteriaceae.
AB  - In the past 2 decades, we have observed a rapid increase of infections due to
      multidrug-resistant Enterobacteriaceae. Regrettably, these isolates possess genes
      encoding for extended-spectrum beta-lactamases (e.g., blaCTX-M, blaTEM, blaSHV)
      or plasmid-mediated AmpCs (e.g., blaCMY) that confer resistance to last
      generation cephalosporins. Furthermore, other resistance traits against
      quinolones (e.g., mutations in gyrA and parC, qnr elements) and aminoglycosides
      (e.g., aminoglycosides modifying enzymes and 16S rRNA methylases) are also
      frequently co-associated. Even more concerning is the rapid increase of
      Enterobacteriaceae carrying genes conferring resistance to carbapenems (e.g.,
      blaKPC, blaNDM). Therefore, the spread of these pathogens puts in peril our
      antibiotic options. Unfortunately, standard microbiological procedures require
      several days to isolate the responsible pathogen and to provide correct
      antimicrobial susceptibility test results. This delay impacts the rapid
      implementation of adequate antimicrobial treatment and infection control
      countermeasures. Thus, there is emerging interest in the early and more sensitive
      detection of resistance mechanisms. Modern non-phenotypic tests are promising in
      this respect, and hence, can influence both clinical outcome and healthcare
      costs. In this review, we present a summary of the most advanced methods (e.g.,
      next-generation DNA sequencing, multiplex PCRs, real-time PCRs, microarrays,
      MALDI-TOF MS, and PCR/ESI MS) presently available for the rapid detection of
      antibiotic resistance genes in Enterobacteriaceae. Taking into account speed,
      manageability, accuracy, versatility, and costs, the possible settings of
      application (research, clinic, and epidemiology) of these methods and their
      superiority against standard phenotypic methods are discussed. 

PMID- 24091108
TI  - Practical insights into enhanced management of patients with HCV infection with
      direct antiviral agents.

PMID- 24091107
TI  - Dexamethasone accelerates degradation of aryl hydrocarbon receptor (AHR) and
      suppresses CYP1A1 induction in placental JEG-3 cell line.
AB  - The JEG-3 choriocarcinoma cell line has been proposed as a model cell line of
      human placental trophoblast for induction studies via aryl hydrocarbon receptor
      (AHR). We examined whether glucocorticoid dexamethasone influences AHR-mediated
      induction of CYP1A1 enzyme in the JEG-3 cell line. We found that dexamethasone
      dose- and time-dependently suppresses CYP1A1 transactivation in gene reporter
      assays, CYP1A1 mRNA induction, and upregulation of 7-ethoxyresorufin-O-deethylase
      (EROD) activity by 3-methylcholanthrene (MC) and 2,3,7,8-tetrachlorodibenzo-p
      dioxin (TCDD) in JEG-3 cells. Co-transfection of JEG-3 cells with glucocorticoid
      receptor (GR) expression construct and treatment with dexamethasone abolished the
      effect of MC on CYP1A1 promoter construct in transient transfection gene reporter
      assays. RU486, a GR antagonist, suppressed the effect of dexamethasone on MC
      induced transactivation of AHR responsive reporter constructs. We also found that
      dexamethasone stimulates both ligand-dependent and ligand-independent degradation
      of AHR but not of aryl hydrocarbon receptor nuclear translocator (ARNT) protein
      in JEG-3 cells. In experiments with proteasome inhibitors MG132 and bortezomib,
      we found that the degradation is not sensitive to proteasome inhibition in JEG-3.
      We can conclude that dexamethasone suppresses AHR-mediated CYP1A1 induction in
      JEG-3 cells through the unique mechanism of AHR-GR crosstalk, which involves
      accelerated degradation of AHR. 

PMID- 24091109
TI  - HCV burden in Europe and the possible impact of current treatment.
AB  - An important proportion of hepatitis C virus patients in Europe are unaware of
      their condition with substantial discrepancies between European countries in
      terms of hepatitis C virus screening. Factors contributing to low screening rates
      likely include limited physician awareness, reluctance of patients to admit to
      unsafe past behaviours, and lack of efficient public health policy for HVC
      screening. It becomes urgent to define innovative public health policy to improve
      hepatitis C virus screening that is the only choice allowing non-tested hepatitis
      C virus patients access to therapy as hepatitis C virus patients remain
      undiagnosed until they develop advanced liver disease. European health
      authorities should encourage innovative approaches to increase the proportion of
      hepatitis C virus persons aware of their condition, such as those proposed
      recently by the Centers for Disease Control and Prevention. Antiviral treatment
      will impact on hepatitis C virus-related morbidity and mortality with marked
      differences between European countries. In genotype 1 patients, protease
      inhibitors-based triple therapy would considerably impact the hepatitis C virus
      related incidence of cirrhosis and deaths. There is an urgent need for the
      reinforcement of hepatitis C virus screening and access to therapy when
      considering their major impact on hepatitis C virus-related morbidity and
      mortality. In Europe, although clinicians from different countries are using the
      same therapies, impact on morbidity and mortality across countries will
      significantly vary. 

PMID- 24091110
TI  - Optimizing DAA management in daily practice.
AB  - Despite the incontestable benefits of telaprevir and boceprevir-based triple
      therapy in patients infected with genotype 1, the practitioner faces a number of
      new challenges. In daily clinical practice, a checklist approach may facilitate
      the management of triple therapy. Before initiation, several specific issues
      should be reviewed with the patient in order to optimize adherence and treatment
      outcome: potential drug to drug interaction, treatment duration and stopping
      rules, possible treatment outcomes, side effects, dose and administration with
      food advice, management of side effects. Because treatment failure is associated
      with the emergence of resistance-associated variants with reduced sensitivity to
      protease inhibitors, adherence is of major importance. In this setting, the role
      of educational nurse should be emphasized for the management of triple therapy in
      daily clinical practice. 

PMID- 24091111
TI  - The importance of HCV RNA measurement for tailoring treatment duration.
AB  - The introduction of telaprevir and boceprevir in the treatment of chronically HCV
      genotype 1 infected patients has led to substantially improved sustained
      virologic response rates and shorter treatment duration for a growing group of
      patients. Management and monitoring of patients receiving protease inhibitor
      based triple therapy is of major importance and has become more complicated.
      Close monitoring of HCV RNA levels for patients on protease inhibitor-based
      therapy to identify subjects who are eligible for shortening of treatment
      duration, are virological non-responders or are in danger of experiencing a viral
      breakthrough is strongly recommended. Several virological tools including
      qualitative and quantitative HCV RNA assays for detection and quantification of
      HCV RNA are commercially available. We review these methods and their
      implications for HCV therapy as well as current sustained virologic response
      definition, stopping rules and recommendations for protease inhibitor-based
      treatment durations. 

PMID- 24091112
TI  - Preparing the patient for success: treat or wait?
AB  - Hepatitis C is a frequent cause of liver cirrhosis and, hepatocellular carcinoma
      worldwide. However, predicting clinical outcomes in patients with chronic
      hepatitis C is challenging. The risk of disease progression is not linear and can
      be associated with several factors. With the currently available therapies,
      around 70% of naive patients, independently of hepatitis C virus genotype can
      achieve a sustained virologic response. Consequently, all hepatitis C virus
      patients are candidates for antiviral therapy. The decision to treat a patient
      with chronic hepatitis C virus infection is based on several factors, including
      the natural history of the disease, the stage of fibrosis, and the efficacy and
      adverse effects related to therapy. The decision to treat immediately or wait for
      a new drug is more difficult and should be tailored to each patient, taking into
      account the patient's characteristics, the risk of disease progression, the
      patient's wishes, and the experience of the attending physician. 

PMID- 24091113
TI  - Management of anaemia and other treatment complications.
AB  - Antiviral treatment for hepatitis C virus infection has dramatically changed with
      the advent of triple therapy including telaprevir or boceprevir, which is
      associated with a new spectrum of adverse events. These may lead to dosage
      reduction and early discontinuation of therapy. An increase in the frequency and
      severity of anaemia was reported in clinical trials for both drugs, and skin
      disorders including rash and pruritus occurred more frequently with the
      telaprevir-based regimen. The first-line management of anaemia is ribavirin dose
      reductions. In cirrhotic patients, aggressive ribavirin dosage reductions,
      erythropoietin alpha and blood transfusions are effective in managing anaemia.
      Several deaths and cases of severe infections and hepatic decompensation were
      reported in cirrhotics treated in real-life setting. Patients with platelet count
      <= 100,000/mm(3) and serum albumin < 35 g/L should not be treated with triple
      therapy as it is related to a high risk of developing severe complications. The
      management of rashes, if well planned, does not require telaprevir
      discontinuation. However, approximately 5% of rashes were severe and a few cases
      were classified as severe cutaneous adverse reactions leading to treatment
      discontinuation. Successful treatment can be enhanced by a strong patient support
      network including a multidisciplinary team.

PMID- 24091114
TI  - The importance of drug-drug interactions in the DAA era.
AB  - With the licensing of the direct acting antivirals telaprevir and boceprevir the
      topic of drug-drug interactions has come to the forefront. These first generation
      hepatitis C virus protease inhibitors are metabolized by and inhibit the key drug
      metabolizing enzyme CYP3A4, which means that knowledge of drug-drug interactions
      has become an essential component of the evaluation of a patient starting triple
      therapy. The number of potential co-medications means that many drugs will be
      used in hepatitis C virus patients where there are no pharmacokinetic study data.
      Here we have to use the data that are available and seek to extrapolate to
      unstudied drugs using key principles of clinical pharmacology (disposition
      characteristics, concentration-effect relationships, therapeutic window) in order
      to give some guidance for management of patients. This is a rapidly moving area
      in hepatitis C therapy, both in terms of understanding the drug interaction
      profile of telaprevir and boceprevir, interaction mechanisms that sometimes
      appear counterintuitive and that may involve enzymes other than CYP3A4 or
      transporters, but then seeking to understand the interaction potential of the
      next wave of drugs that will soon be with us. 

PMID- 24091115
TI  - Treatment of chronic hepatitis C virus infection after liver transplantation.
AB  - Chronic hepatitis C virus infection is a leading cause of end stage liver disease
      and one of the leading indications for liver transplantation. Furthermore,
      hepatitis C virus recurrence is universal post-transplant leading to decreased
      graft and patient survival. Recurrent disease related to hepatitis C virus can
      lead to between 20 and 30% of patients developing recurrent cirrhosis within 5
      years. Treatment options with antiviral therapy are limited and are associated
      with a significant side-effect profile, suboptimal tolerability and inferior
      response rates. Attention has therefore turned to strategies that can reduce
      hepatitis C virus recurrence rates post-transplant. Approximately only 30% of
      patients will achieve a sustained virologic response with current therapy with
      pegylated interferon and ribavirin. Successful hepatitis C virus eradication is
      the only factor associated with improved graft and patient survival post liver
      transplantation. Here we provide an overview of antiviral treatment in patients
      in the transplant arena and the potential opportunities and challenges with the
      introduction of new directly acting antivirals in G1 patients. 

PMID- 24091116
TI  - Optimizing treatment in HIV/HCV coinfection.
AB  - Sustained virological response (SVR) to anti-hepatitis C virus (HCV) treatment is
      an outcome that can improve life expectancy in persons with human
      immunodeficiency virus (HIV) infection. Results of anti-HCV treatment are poor,
      and less than 50% of treated patients show SVR to peginterferon plus ribavirin
      combination therapy; in infections from HCV genotype 1 this proportion is less
      than 40%. Pilot studies have demonstrated that Boceprevir or Telaprevir in
      combination with peginterferon plus ribavirin are able to increase the SVR rate
      from 45% to 74% with Telaprevir, and from 26% to 61% with Boceprevir in persons
      never treated for hepatitis C. Interim data seem to indicate a high rate of HCV
      RNA undetectability on treatment also in patients without sustained response to
      peginterferon plus ribavirin. Both Telaprevir and Boceprevir have drug-drug
      interactions with antiretrovirals, and options for concurrent antiretroviral
      therapy are restricted. There are also several new anti-HCV drugs under study
      with the potential for more tolerable effective future regimens. The indication
      for treatment in a patient with HCV/HIV coinfection should take into account the
      priority of treatment, the probability of sustained response, the potential
      toxicities, the concurrent antiretroviral therapy options, the patient's
      motivation, and the sustainability of current and future therapies. 

PMID- 24091117
TI  - Safety of direct antiviral agents in real life.
AB  - Advanced liver fibrosis is a recognized barrier to both access and response to
      triple therapy with protease inhibitors Boceprevir and Telaprevir, and is
      associated with an increased risk of severe treatment-related adverse events.
      While not properly addressed by registration trials enrolling highly selected
      populations, this nuance of protease inhibitors triple therapy for hepatitis C
      virus genotype 1 was highlighted by the observational study CUPIC conducted in
      France. The study enrolled a large number of patients, beyond the safety criteria
      of registration trials, thereby ending in worrisome safety profiles of protease
      inhibitors regimens in patients with severe liver impairment who in the past had
      safely, but unsuccessfully, been exposed to dual therapy with interferon and
      ribavirin. Indeed, protease inhibitors therapy led to alarming rates of infection
      and clinical decompensation, particularly in patients with reduced hepatic
      reserve as predicted by the low platelets and albumin levels. Ultimately
      antiviral therapy resulted in a death rate of up to 2% and a treatment
      discontinuation rate of 26%, not to mention the increased need of bone marrow
      stimulating factors and blood transfusions. The 16-week interim report of the
      HEP3002 trial expanded the access program to Telaprevir, enrolling patients with
      advanced fibrosis who fulfilled the safety criteria of registration trials only,
      and offered an unbiased evaluation of Telaprevir tolerability and safety in this
      most in-need population, since the rates of treatment discontinuation due to
      adverse events were up to 14%. 

PMID- 24091118
TI  - A review on removing pharmaceutical contaminants from wastewater by constructed
      wetlands: design, performance and mechanism.
AB  - This paper presents a comprehensive review of the current state of research
      activities on the application of constructed wetlands for removing pharmaceutical
      contaminants from wastewater. The focus of the review was placed on the
      application of constructed wetlands as an alternative secondary wastewater
      treatment system or as a wastewater polishing treatment system. The design
      parameters of the reported constructed wetlands including the physical
      configuration, hydraulic mode, vegetation species, and targeting pharmaceuticals
      were summarized. The removal efficiencies of pharmaceuticals under different
      conditions in the wetlands were evaluated at the macroscopic level. In addition,
      the importance of the three main components of constructed wetlands (substrate,
      plants and microbes) for pharmaceutical removal was analyzed to elucidate the
      possible removal mechanisms involved. There is a general consensus among many
      researchers that constructed wetlands hold great potential of being used as an
      alternative secondary wastewater treatment system or as a wastewater polishing
      treatment system for the removal of pharmaceuticals, but relevant reported
      studies are scarce and are not conclusive in their findings. Current knowledge is
      limited on the removal efficiencies of pharmaceuticals in constructed wetlands,
      the removal mechanisms involved, the toxicity to constructed wetlands caused by
      pharmaceuticals, and the influences of certain important parameters
      (configuration design, hydraulic mode, temperature and seasonality, pH, oxygen
      and redox potential, etc.). This review promotes further research on these issues
      to provide more and better convincing evidences for the function and performance
      of larger laboratory-scale, pilot-scale or full-scale constructed wetlands. 

PMID- 24091119
TI  - Signs and symptoms of methylmercury contamination in a First Nations community in
      Northwestern Ontario, Canada.
AB  - In 1970, fish caught in the English-Wabigoon River system in northwestern
      Ontario, Canada, were found to be contaminated with mercury coming from a chlor
      alkali plant in the province. In the 1970s, patients exhibiting some of the
      symptoms of the Hunter-Russell syndrome (e.g. paresthesias, visual field
      constriction, ataxia, impaired hearing, and speech impairment) were reported by
      some researchers. However attempts to diagnose the patients as suffering from
      methylmercury poisoning proved to be controversial. In order to research the
      presence of methylmercury contamination, and show that the patients, through
      eating contaminated fish, were suffering from methylmercury poisoning, we studied
      the results of subjective complaints, neurological findings, and quantitative
      somatosensory measurements gathered in Grassy Narrows Indian Reservation,
      Ontario, in March, 2010. At that time, the population of the Grassy Narrows
      settlement was around 900. Ninety-one residents volunteered to be examined. From
      them, we selected 80 people who were older than 15 years old, and divided them
      into two groups. Canadian Younger (CY): 36 residents who were from 16 to 45 years
      old. Canadian Older (CO): 44 residents who were from 46 to 76 years old. We
      compared them to Japanese Exposed (JE): 88 methylmercury exposed residents from
      the Minamata district in Japan, and Japanese Control (JC): 164 control residents
      from non-polluted areas in Japan. Complaints and abnormal neurological findings
      were more prevalent and quantitative sensory measurements were worse in the two
      Canadian groups and the Japanese Exposed group than in the Japanese Control
      group. Complaints, neurological findings and quantitative sensory measurements
      were similar in Canadian Older and Japanese Exposed. The results for Canadian
      Younger fell between those of Canadian Older and Japanese Control. These findings
      indicate that the clinical signs and symptoms of the residents of Grassy Narrows
      are almost the same as those recorded for Minamata disease in Japan.

PMID- 24091120
TI  - Particle size, surface charge and concentration dependent ecotoxicity of three
      organo-coated silver nanoparticles: comparison between general linear model
      predicted and observed toxicity.
AB  - Mechanism underlying nanotoxicity has remained elusive. Hence, efforts to
      understand whether nanoparticle properties might explain its toxicity are
      ongoing. Considering three different types of organo-coated silver nanoparticles
      (AgNPs): citrate-coated AgNP, polyvinylpyrrolidone-coated AgNP, and branched
      polyethyleneimine-coated AgNP, with different surface charge scenarios and core
      particle sizes, herein we systematically evaluate the potential role of particle
      size and surface charge on the toxicity of the three types of AgNPs against two
      model organisms, Escherichia coli and Daphnia magna. We find particle size,
      surface charge, and concentration dependent toxicity of all the three types of
      AgNPs against both the test organisms. Notably, Ag(+) (as added AgNO3) toxicity
      is greater than each type of AgNPs tested and the toxicity follows the trend:
      AgNO3 > BPEI-AgNP > Citrate-AgNP > PVP-AgNP. Modeling particle properties using
      the general linear model (GLM), a significant interaction effect of primary
      particle size and surface charge emerges that can explain empirically-derived
      acute toxicity with great precision. The model explains 99.9% variation of
      toxicity in E. coli and 99.8% variation of toxicity in D. magna, revealing
      satisfactory predictability of the regression models developed to predict the
      toxicity of the three organo-coated AgNPs. We anticipate that the use of GLM to
      satisfactorily predict the toxicity based on nanoparticle physico-chemical
      characteristics could contribute to our understanding of nanotoxicology and
      underscores the need to consider potential interactions among nanoparticle
      properties when explaining nanotoxicity.

PMID- 24091121
TI  - Occurrence of surfactants in wastewater: hourly and seasonal variations in urban
      and industrial wastewaters from Seville (Southern Spain).
AB  - Surfactants are daily discharged to the environment from urban and industrial
      activities. The assessment of the risk derived from the presence of these
      compounds in the environment requires a deep knowledge about their sources and
      their distribution in wastewater treatment plants (WWTPs). However, in spite of
      several studies reporting their presence in WWTPs, only a small number is focused
      on their different sources. In this work, the distribution of anionic (linear
      alkylbenzene sulfonates) and non-ionic (nonylphenol ethoxylates) surfactants in
      WWTPs and in urban and industrial wastewater collection systems has been
      investigated. Seasonal and daily variability was also assessed. Concentrations of
      linear alkylbenzene sulfonates in influent and effluent wastewaters ranged from
      1155 to 9200 MUg L(-1), and from below limit of detection to 770 MUg L(-1),
      respectively, whereas the concentrations of nonylphenol ethoxylates were
      significantly lower. Linear alkylbenzene sulfonates were efficiently removed
      (>96%), while mean removal rates of nonylphenol ethoxylates were significantly
      lower (<20%). Studies carried out in different seasons revealed seasonal
      discharge patterns from both urban and industrial activities. The analysis of
      wastewater collection systems showed a major contribution of linear alkylbenzene
      sulfonates from urban areas while, in the case of nonylphenol ethoxylates, their
      major contribution came from industrial activities. In all cases the discharge
      patterns of surfactants were related with the water consumption.

PMID- 24091122
TI  - alpha-Pinene, 3-carene and d-limonene in indoor air of Polish apartments: the
      impact on air quality and human exposure.
AB  - Monoterpenes are among most ubiquitous volatile organic compounds (VOCs) to be
      detected in indoor air. Since the quality of indoor air is considered important
      for inhabitants' well-being, the present study aimed at investigating impact of
      human activity on levels of selected monoterpenes applying passive sampling
      technique followed by thermal desorption and gas chromatography coupled mass
      spectrometry. One of the objectives of the present work was to identify and
      characterize main emission sources as well as to investigate relationship between
      selected monoterpenes in indoor air. Concentration levels obtained for studied
      monoterpenes varied from 3 MUg m(-3) for 3-carene to 1261 MUg m(-3) for d
      limonene. D-limonene was reported the most abundant of studied monoterpenes in
      indoor air. The strong correlation observed between monoterpenes suggests that
      studied compounds originate from same emission sources, while the I/O >1 proves
      the strong contribution of endogenous emission sources. The in-depth study of day
      night fluctuations in concentrations of monoterpenes lead to the conclusion that
      human presence and specific pattern of behavior strongly influences presence and
      concentrations of VOCs in indoor environment. The evaluation of human exposure to
      selected monoterpenes via inhalation of air revealed that infants, toddlers and
      young children were the highly exposed individuals.

PMID- 24091123
TI  - Vacuum ultraviolet photolysis of diclofenac and the effects of its treated
      aqueous solutions on the proliferation and migratory responses of Tetrahymena
      pyriformis.
AB  - The effects of dissolved O2, phosphate buffer and the initial concentration of
      diclofenac on the vacuum ultraviolet photolysis of this contaminant molecule were
      studied. Besides kinetic measurements, the irradiated, multicomponent samples
      were characterized via the proliferation and migratory responses (in sublethal
      concentrations) of the bioindicator eukaryotic ciliate Tetrahymena pyriformis.
      The results suggest that hydroxyl radicals, hydrogen atoms and hydroperoxyl
      radicals may all contribute to the degradation of diclofenac. The aromatic by
      products of diclofenac were presumed to include a hydroxylated derivative, 1-(8
      chlorocarbazolyl)acetic acid and 1-(8-hydroxycarbazolyl)acetic acid. The
      biological activity of photoexposed samples reflected the chemical transformation
      of diclofenac and was also dependent on the level of dissolved O2. The increase
      in toxicity of samples taken after different irradiation times did not exceed a
      factor of two. Our results suggest that the combination of vacuum ultraviolet
      photolysis with toxicity and chemotactic measurements can be a valuable method
      for the investigation of the elimination of micropollutants. 

PMID- 24091124
TI  - Use of portable exposure meters for comparing mobile phone base station radiation
      in different types of areas in the cities of Basel and Amsterdam.
AB  - BACKGROUND: Radiofrequency electromagnetic fields (RF-EMF) are highly variable
      and differ considerably within as well as between areas. Exposure assessment
      studies characterizing spatial and temporal variation are limited so far. Our
      objective was to evaluate sources of data variability and the repeatability of
      daily measurements using portable exposure meters (PEMs). METHODS: Data were
      collected at 12 days between November 2010 and January 2011 with PEMs in four
      different types of urban areas in the cities of Basel (BSL) and Amsterdam (AMS).
      RESULTS: Exposure from mobile phone base stations ranged from 0.30 to 0.53 V/m in
      downtown and business areas and in residential areas from 0.09 to 0.41 V/m.
      Analysis of variance (ANOVA) demonstrated that measurements from various days
      were highly reproducible (measurement duration of approximately 30 min) with only
      0.6% of the variance of all measurements from mobile phone base station radiation
      being explained by the measurement day and only 0.2% by the measurement time
      (morning, noon, afternoon), whereas type of area (30%) and city (50%) explained
      most of the data variability. CONCLUSIONS: We conclude that mobile monitoring of
      exposure from mobile phone base station radiation with PEMs is useful due to the
      high repeatability of mobile phone base station exposure levels, despite the high
      spatial variation.

PMID- 24091125
TI  - Enhanced photoelectrocatalytic performance of titanium dioxide/carbon cloth based
      photoelectrodes by graphene modification under visible-light irradiation.
AB  - Reduced graphene oxide nanosheets modified TiO2 nanospheres on carbon cloth
      electrodes (RGO/TiO2/CC) have been fabricated and used for photoelectrocatalytic
      (PEC) degradation of organic pollutants under visible light irradiation. The
      fabricated RGO/TiO2/CC electrodes were characterized by scanning electron
      microscopy (SEM), X-ray diffraction (XRD), X-ray photoelectron spectroscopy
      (XPS), and UV-vis diffuse reflectance spectroscopy. Compared with TiO2/CC
      electrode, the RGO modified TiO2/CC electrode evidently shows improved visible
      light-driven PEC activity for degradation of an often used model pollutant,
      methylene blue (MB). Moreover, the efficiency of MB degradation by PEC process
      (0.0133 min(-1)) is about 13-fold and 7-fold faster than that of electrochemical
      process (0.001 min(-1)) and photocatalytic process (0.0018 min(-1)),
      respectively. The improved catalytic activity for PEC degradation of MB
      pollutants could be attributed to the existence of RGO, which extends the
      absorption onset of TiO2 to longer wavelength direction and promotes the
      separation of electron-hole pairs generated under visible light irradiation. The
      promotion effect on the electron-hole separation is supported by photocurrent and
      electrochemical impedance measurements. In addition, a synergetic effect of
      photocatalysis and electrocatalysis is involved in the PEC process, by which the
      recombination of photogenerated electron-hole pairs is significantly suppressed.

PMID- 24091126
TI  - Geogenic arsenic and other trace elements in the shallow hydrogeologic system of
      Southern Poopo Basin, Bolivian Altiplano.
AB  - Environmental settings in the southern area of Lake Poopo in the Bolivian
      highlands, the Altiplano, have generated elevated amounts of arsenic (As) in the
      water. The area is characterised by a semiarid climate, slow hydrological flow
      and geologic formations of predominantly volcanic origin. The present study aimed
      at mapping the extent of the water contamination in the area and to investigate
      the geogenic sources and processes involved in the release of As to the
      groundwater. Ground- and surface-water samples were collected from 24 different
      sites, including drinking water wells and rivers, in the southern Poopo basin in
      two different field campaigns during the dry and rainy seasons. The results
      revealed variable levels of As in shallow drinking water wells and average
      concentration exceeding the WHO guidelines value. Arsenic concentrations range
      from below 5.2 MUg/L (the detection level) to 207 MUg/L and averages 72 MUg/L.
      Additionally, high boron (B) concentrations (average 1902 MUg/L), and high
      salinity are further serious concerns for deteriorating the groundwater quality
      and rendering it unsuitable for drinking. Groundwater is predominantly of the Na
      Cl-HCO3 type or the Ca-Na-HCO3 type with neutral or slightly alkaline pH and
      oxidising character. While farmers are seriously concerned about the water
      scarcity, and on a few occasions about salinity, there are no concerns about As
      and B present at levels exceeding the WHO guidelines, and causing negative long
      term effects on human health. Sediment samples from two soil profiles and a river
      bed along with fourteen rock samples were also collected and analysed. Sequential
      extractions of the sediments together with the calculation of the mineral
      saturation indices indicate that iron oxides and hydroxides are the important
      secondary minerals phases which are important adsorbents for As. High pH values,
      and the competition of As with HCO3 and dissolved silica for the adsorption sites
      probably seems to be an important process for the mobilisation of As in the
      shallow groundwaters of the region. Continuous monitoring and expansion of
      monitoring systems are necessary prerequisites for better understanding of the
      pattern of As mobilisation in the Southern Poopo Basin.

PMID- 24091127
TI  - Pathological features and survival outcomes of very young patients with early
      breast cancer: how much is "very young"?
AB  - We collected information on 497 consecutive breast cancer patients aged less than
      35 years operated at the European Institute of Oncology. The main aim of the
      study is to compare biological and clinical features dividing the population by
      age: <25 years, 25-29 and 30-34 years old. Pattern of recurrence and survival
      were also analyzed. Patients aged <25 years had 81.8% poorly differentiated
      tumors compared with 66.7% and 56.5% in the 25-29 and 30-34 groups, respectively;
      no other significant difference were found in the distribution of clinical and
      immunohistochemical features The distribution of Luminal A and B, Triple Negative
      and HER2 subtypes (immunohistochemically defined) was not statistically different
      among the three age groups. No difference was found in the incidence of loco
      regional relapses, distant metastases, disease-free survival (p = 0.79) and
      overall survival (p = 0.99) between the three age groups. This latter findings
      was confirmed using age as a continuous variable assuming a linear association
      between age and the outcomes considered, too. In conclusion, our data indicate
      that the group of patients with breast cancer below 35 years is essentially a
      homogenous group when classical clinical and immunohistochemical features were
      considered. 

PMID- 24091128
TI  - A multicenter phase I-II study of docetaxel plus epirubicin plus bevacizumab as
      first-line treatment in women with HER2-negative metastatic breast cancer.
AB  - PURPOSE: To assess the efficacy and toxicity of docetaxel (D) plus epirubicin (E)
      in combination with bevacizumab (B) [DEB regimen] as front-line treatment in
      patients with metastatic breast cancer (MBC). PATIENTS AND METHODS: Women with
      previously untreated HER2-negative MBC received B (15 mg/kg), E (75 mg/m2) and D
      (75 mg/m2) with prophylactic G-CSF support every 3 weeks (q3w) for up to 9 cycles
      followed by B (15 mg/kg q3w) until disease progression. Primary endpoint was the
      overall response rate (ORR). Circulating tumor cells (CTCs) were evaluated using
      the CellSearch system at different time points during therapy. RESULTS: Eighty
      three women were enrolled with median age 62 years, performance status 0-1 in
      93%, triple negative disease in 12% and liver metastases in 47%. In an intention
      to treat analysis, complete response was achieved in 13 (15.7%) and partial
      response in 42 (50.6%) (overall response rate 66.3%; 95% CI 56.09-76.44%). The
      median time to progression was 20.1 months and the 1-year overall survival rate
      82.3%. Grade 3-4 neutropenia occurred in 37%, febrile neutropenia in 10%, anemia
      in 4%, thrombocytopenia in 2% and diarrhea in 2% of patients. There were two
      deaths possibly related to study treatment (sigmoid perforation n = 1; sudden
      death n = 1). Moreover, one patient developed pulmonary embolism and another one
      myocardial infarction while on treatment. Although DEB administration
      significantly reduced the proportion of patients presenting CTCs, the detection
      of >=5 or >=1 CTCs before treatment initiation was significantly associated with
      worse progression-free survival (p = 0.001 and p = 0.004) and overall survival (p
      = 0.001 and p = 0.027), respectively. CONCLUSIONS: The DEB regimen is a very
      active but also potentially toxic combination in MBC. Detection of CTCs before
      treatment is associated with worse outcome. CLINICALTRIALSGOV: NCT00705315.

PMID- 24091129
TI  - Totally resistant tuberculosis: will antileprosy drugs be helpful?

PMID- 24091130
TI  - Detection of chromosomal blaCTX-M-15 in Escherichia coli O25b-B2-ST131 isolates
      from the Kinki region of Japan.
AB  - Escherichia coli O25b-B2-ST131 isolates harbouring bla(CTX-M-15) are distributed
      worldwide. The bla(CTX-M-15) transposition unit has often been found on plasmids
      and the genetic contexts have been examined; however, less is known about the
      frequency and contexts of the bla(CTX-M-15) transposition unit on the chromosome.
      This study was performed to determine the chromosomal location of the bla(CTX-M
      15) transposition unit and to analyse the molecular structure of the region
      surrounding the bla(CTX-M-15) transposition unit in E. coli O25b-B2-ST131
      isolates. Twenty-two E. coli O25b-B2-ST131 strains harbouring bla(CTX-M-15) that
      had been isolated from university hospital patients and nursing home residents in
      the Kinki region of Japan were examined. Inverse PCR (iPCR) targeting bla(CTX-M
      15) was performed to classify the molecular structure of the region surrounding
      the bla(CTX-M-15) transposition unit. The isolates were classified into nine
      types (types A-I) considering the iPCR results; type A was the most prevalent
      type (13/22 isolates). Sequences of the iPCR-amplified DNA fragments showed that
      the bla(CTX-M-15) transposition unit consisted of ISEcp1, bla(CTX-M-15) and
      orf477Delta. A homology search of the obtained sequences showed that the bla(CTX
      M-15) transposition unit was inserted into different chromosomal regions in eight
      of the nine classified types. Although 21 of the 22 E. coli isolates possessed
      chromosomally located bla(CTX-M-15) transposition units, clonal spread was not
      evident on pulsed-field gel electrophoresis (PFGE) analysis. Taken together,
      these data indicate that certain E. coli O25b-B2-ST131 strains harbouring
      chromosomal bla(CTX-M-15) have emerged and spread in the Kinki region of Japan.

PMID- 24091131
TI  - Variation in antibiotic susceptibility of uropathogens by age among ambulatory
      pediatric patients.
AB  - We compared uropathogen antibiotic susceptibility across age groups of ambulatory
      pediatric patients. For Escherichia coli (n=5,099) and other Gram-negative rods
      (n=626), significant differences (p<0.05) existed across age groups for
      ampicillin, cefazolin, and trimethoprim/sulfamethoxazole susceptibility. In E.
      coli, differences in trimethoprim/sulfamethoxazole susceptibility varied from 79%
      in children under 2 to 88% in ages 16-18 (p<0.001), while ampicillin
      susceptibility varied from 30% in children under 2 to 53% in ages 2-5 (p=0.015).
      Uropathogen susceptibility to common urinary anti-infectives may be lower in the
      youngest children. Further investigation into these differences is needed to
      facilitate appropriate and prudent treatment of urinary tract infections.

PMID- 24091132
TI  - Low-intensity pulsed ultrasound (LIPUS) inhibits LPS-induced inflammatory
      responses of osteoblasts through TLR4-MyD88 dissociation.
AB  - Previous reports have shown that osteoblasts are mechano-sensitive. Low-intensity
      pulsed ultrasound (LIPUS) induces osteoblast differentiation and is an
      established therapy for bone fracture. Here we have examined how LIPUS affects
      inflammatory responses of osteoblasts to LPS. LPS rapidly induced mRNA expression
      of several chemokines including CCL2, CXCL1, and CXCL10 in both mouse osteoblast
      cell line and calvaria-derived osteoblasts. Simultaneous treatment by LIPUS
      significantly inhibited mRNA induction of CXCL1 and CXCL10 by LPS. LPS-induced
      phosphorylation of ERKs, p38 kinases, MEK1/2, MKK3/6, IKKs, TBK1, and Akt was
      decreased in LIPUS-treated osteoblasts. Furthermore, LIPUS inhibited the
      transcriptional activation of NF-kappaB responsive element and Interferon
      sensitive response element (ISRE) by LPS. In a transient transfection experiment,
      LIPUS significantly inhibited TLR4-MyD88 complex formation. Thus LIPUS exerts
      anti-inflammatory effects on LPS-stimulated osteoblasts by inhibiting TLR4 signal
      transduction. 

PMID- 24091133
TI  - A signal-amplification circuit between miR-218 and Wnt/beta-catenin signal
      promotes human adipose tissue-derived stem cells osteogenic differentiation.
AB  - Human adipose-derived stem cells (hASCs) have become a highly attractive source
      of seed cells in bone regenerative. It has become a key issue how to effectively
      improve osteogenic differentiation of hASCs in the bone tissue engineering.
      Numerous regulatory pathways dominate osteogenic differentiation of hASCs involve
      transcriptional factors and signaling molecules. However, how these factors
      combine with each other to regulate hASCs osteogenic differentiation still remain
      to be illustrated. The identification of microRNAs will illuminate this and might
      permit finely tuning the osteogenic differentiation process. Here, we present
      evidence that miR-218 acts as a positive regulator of hASCs osteogenesis. Real
      time PCR shows that miR-218 was up-regulated during osteogenic differentiation.
      Overexpression of exogenous miR-218 enhanced osteogenic differentiation in vitro,
      whereas inhibition of miR-218 would suppress osteogenic differentiation.
      Furthermore, miR-218 directly targeted SFRP2 and DKK2, which is a WNT signaling
      pathway antagonist, and enhanced Wnt/beta-catenin signaling activity. Finally, we
      found that mimicking Wnt/beta-catenin signal strengthened the expression level of
      miR-218, while blocking the signal attenuated the expression level of miR-218.
      This feed-forward regulatory circuit provides additional insight into how miRNAs
      acting as a signal amplifier interact with signal molecules during hASCs
      osteogenic differentiation. Taken together, we have established a regulatory
      network with a central role for the miR-218 in hASCs osteogenic differentiation. 

PMID- 24091134
TI  - Early safety assessment of human oculotoxic drugs using the zebrafish visualmotor
      response.
AB  - INTRODUCTION: Many prescribed drugs can adversely affect the eye by causing
      damage to the function of visual pathways or toxicity to the retina. Zebrafish
      have the potential to efficiently predict drugs with adverse ocular effects at
      pre-clinical stages of development. In this study, we explore the potential of
      using a semi-automated visual behaviour assay to predict drug-induced ocular
      toxicity in wild-type zebrafish larvae. METHODS: 3 dpf larvae were treated with
      six known oculotoxic drugs and five control drugs in embryo medium containing
      0.1% DMSO. After 48 h, larvae were assessed using the visualmotor response (VMR),
      an assay which quantifies locomotor responses to light changes; the optokinetic
      response (OKR), a behavioural assay that quantifies saccadic eye responses to
      rotating stimuli; and the touch response, a locomotor response to tactile
      stimuli. RESULTS: 9 of 10 negative control drugs had no effect on zebrafish
      visual behaviour. 5 of the 6 known oculotoxic drugs (digoxin, gentamicin,
      ibuprofen, minoxidil and quinine) showed adverse effects on zebrafish visual
      behaviour assessed by OKR or the more automated VMR. No gross morphological
      changes were observed in treated larvae. The general locomotor activity of
      treated larvae, tested using the touch response assay, showed no differences with
      respect to controls. Overall the VMR assay had a sensitivity of 83%, a
      specificity of 100% and a positive predictive value of 100%. DISCUSSION: This
      study confirms the suitability of the VMR assay as an efficient and predictive
      pre-clinical approach to evaluate adverse ocular effects of drugs on visual
      function in vivo.

PMID- 24091135
TI  - Response to: making WAAVES in the vocalization community: how big is the splash?

PMID- 24091136
TI  - Water-tight membranes from neuronal morphology files.
AB  - We present an algorithm to form watertight 3D surfaces consistent with the point
      and-diameter based neuronal morphology descriptions widely used with spatial
      electrophysiology simulators. Such morphology descriptions are readily available
      online and may come from light-microscopy tracings or from an artificial cell
      grown algorithmically. These files contain only limited information about a
      neuron's full three-dimensional shape, as they consist mostly of a list of points
      and diameters with connectivity data. This representation is well-suited for
      electrophysiology simulations, where the space constants are larger than
      geometric ambiguities. However, the simple interpretations used for pure
      electrophysiological simulation produce geometries unsuitable for multi-scale
      models that also involve three-dimensional reaction-diffusion, as such models
      have smaller space constants. Although one cannot exactly reproduce an original
      neuron's full shape from point-and-diameter data, our new constructive
      tessellated neuronal geometry (CTNG) algorithm uses constructive solid geometry
      to define a plausible reconstruction without gaps or cul-de-sacs. CTNG then uses
      "constructive cubes" to produce a watertight triangular mesh of the neuron
      surface, suitable for use in reaction-diffusion simulations. CTNG provides the
      correspondence between internal voxels and surface triangles, needed to make
      connections between cytoplasmic and membrane mechanisms. Optimization of the
      underlying marching cubes algorithm and distance calculations enhanced the
      performance of constructive cubes for a neuronal geometry, where a large number
      of small objects sparsely occupy a large volume.

PMID- 24091137
TI  - A modified anxious behavior test for hamsters.
AB  - BACKGROUND: Latency to feed in a novel environment assesses anxious behavior in
      rodents, but it is unclear whether it distinguishes anxiety from consumption or
      appetite. NEW METHOD: The anxiety-related feeding/exploration conflict (AFEC)
      test was used here to assess anxious behavior in Syrian hamsters for which
      increased cheek-pouching of food, but not overconsumption of it, reflects
      appetitive drive, and orexigenic stimuli do not increase consumption. The setup
      of the test prevented cheek-pouching. COMPARISON WITH EXISTING METHODS: Latency
      to approach test food provided an additional control for non-emotional effects of
      treatments. Feed and approach latencies in the test cage were normalized to those
      in the home cage to factor out non-emotional effects. RESULTS: Feed latency and
      the feed latency ratio (test cage/home cage) were reduced by acute treatment with
      benzodiazepine, diazepam, or beta-adrenergic receptor antagonist, propranolol, or
      chronic treatment with norepinephrine reuptake inhibitor, desipramine. Reductions
      of feed latency and the feed latency ratio were not associated with hyperphagia,
      and these behaviors were unaltered by acute treatment with opioid receptor
      antagonist, naltrexone. Latency to approach food in the test cage, with and
      without normalization, was unaltered by these treatments. Finally, overnight
      fasting elevated feed latency without hyperphagia, and this effect was attenuated
      by chronic desipramine treatment. CONCLUSIONS: These results suggest that the
      AFEC test assesses anxious, but not appetitive or consummatory, behavior, and
      that its sensitivity increases with food deprivation of hamsters.

PMID- 24091138
TI  - Hand, belt, pocket or bag: Practical activity tracking with mobile phones.
AB  - For rehabilitation and diagnoses, an understanding of patient activities and
      movements is important. Modern smartphones have built in accelerometers which
      promise to enable quantifying minute-by-minute what patients do (e.g. walk or
      sit). Such a capability could inform recommendations of physical activities and
      improve medical diagnostics. However, a major problem is that during everyday
      life, we carry our phone in different ways, e.g. on our belt, in our pocket, in
      our hand, or in a bag. The recorded accelerations are not only affected by our
      activities but also by the phone's location. Here we develop a method to solve
      this kind of problem, based on the intuition that activities change rarely, and
      phone locations change even less often. A hidden Markov model (HMM) tracks
      changes across both activities and locations, enabled by a static support vector
      machine (SVM) classifier that probabilistically identifies activity-location
      pairs. We find that this approach improves tracking accuracy on healthy subjects
      as compared to a static classifier alone. The obtained method can be readily
      applied to patient populations. Our research enables the use of phones as
      activity tracking devices, without the need of previous approaches to instruct
      subjects to always carry the phone in the same location.

PMID- 24091139
TI  - Comparison of manual and semi-automated segmentation methods to evaluate
      hippocampus volume in APP and PS1 transgenic mice obtained via in vivo magnetic
      resonance imaging.
AB  - BACKGROUND: Magnetic resonance imaging (MRI) of transgenic mouse models of
      Alzheimer's disease is valuable to understand better the structural changes that
      occur in the brain and could provide a means to test drug treatments. A hallmark
      pathological feature of Alzheimer's disease is atrophy of the hippocampus, which
      is an early biomarker of the disease. MRI can be used to detect and monitor this
      biomarker. METHOD: Repeated measurements using in vivo 3D T2-weighted imaging of
      mice were used to assess the methods. Each mouse was imaged twice in one week and
      twice the following week and no changes in volume were expected. The hippocampus
      was segmented both manually and semi-automatically. Registration was done to gain
      information on shape changes. The volumes from each mouse were compared intra
      mouse, between mice and to hippocampus volume values in the literature. RESULTS:
      A reliable method was developed which was able to detect difference in volumes of
      hippocampus between mice when performed by a single individual. The semi
      automated segmentation was unable to detect the same level of differences. The
      semi-automated segmentation method gave larger hippocampus volumes, with 78-87%
      reliability between the manual and semi-automated segmentation. Although more
      accurate, the manual segmentation is laborious and suffers from inter- and intra
      variability. CONCLUSION: These results suggest that manual segmentation is still
      considered the most reliable segmentation method for small structures. However,
      if performing longitudinal studies, where there is at least one year between
      imaging sessions, the segmentation should be done all at once at the end of all
      the imaging sessions. If segmentation is done after each imaging session, with at
      least a year passing between segmentations, very small variations in volumes can
      be missed. This method provides a means to quantify the volume of the hippocampus
      in a live mouse using manual segmentation, which is the first step toward
      studying hippocampus atrophy in a mouse model of Alzheimer's disease.

PMID- 24091140
TI  - Fast automated protein NMR data collection and assignment by ADAPT-NMR on Bruker
      spectrometers.
AB  - ADAPT-NMR (Assignment-directed Data collection Algorithm utilizing a
      Probabilistic Toolkit in NMR) supports automated NMR data collection and backbone
      and side chain assignment for [U-(13)C, U-(15)N]-labeled proteins. Given the
      sequence of the protein and data for the orthogonal 2D (1)H-(15)N and (1)H-(13)C
      planes, the algorithm automatically directs the collection of tilted plane data
      from a variety of triple-resonance experiments so as to follow an efficient
      pathway toward the probabilistic assignment of (1)H, (13)C, and (15)N signals to
      specific atoms in the covalent structure of the protein. Data collection and
      assignment calculations continue until the addition of new data no longer
      improves the assignment score. ADAPT-NMR was first implemented on Varian
      (Agilent) spectrometers [A. Bahrami, M. Tonelli, S.C. Sahu, K.K. Singarapu, H.R.
      Eghbalnia, J.L. Markley, PLoS One 7 (2012) e33173]. Because of broader interest
      in the approach, we present here a version of ADAPT-NMR for Bruker spectrometers.
      We have developed two AU console programs (ADAPT_ORTHO_run and ADAPT_NMR_run)
      that run under TOPSPIN Versions 3.0 and higher. To illustrate the performance of
      the algorithm on a Bruker spectrometer, we tested one protein, chlorella
      ubiquitin (76 amino acid residues), that had been used with the Varian version:
      the Bruker and Varian versions achieved the same level of assignment completeness
      (98% in 20 h). As a more rigorous evaluation of the Bruker version, we tested a
      larger protein, BRPF1 bromodomain (114 amino acid residues), which yielded an
      automated assignment completeness of 86% in 55 h. Both experiments were carried
      out on a 500 MHz Bruker AVANCE III spectrometer equipped with a z-gradient 5 mm
      TCI probe. ADAPT-NMR is available at http://pine.nmrfam.wisc.edu/ADAPT-NMR in the
      form of pulse programs, the two AU programs, and instructions for installation
      and use.

PMID- 24091141
TI  - Parallel waves of inductive signaling and mesenchyme maturation regulate
      differentiation of the chick mesonephros.
AB  - The mesonephros is a linear kidney that, in chicken embryos, stretches between
      the axial levels of the 15th to the 30th somites. Mesonephros differentiation
      proceeds from anterior to posterior and is dependent on signals from the nephric
      duct, which migrates from anterior to posterior through the mesonephric region.
      If migration of the nephric duct is blocked, markers of tubule differentiation,
      including Lhx1 and Wnt4, are not activated posterior to the blockade. However,
      activation and maintenance of the early mesonephric mesenchyme markers Osr1, Eya1
      and Pax2 proceeds normally in an anterior-to-posterior wave, indicating that
      these genes are not dependent on inductive signals from the duct. The expression
      of Lhx1 and Wnt4 can be rescued in duct-blocked embryos by supplying a source of
      canonical Wnt signaling, although epithelial structures are not obtained,
      suggesting that the duct may express other tubule-inducing signals in addition to
      Wnts. In the absence of the nephric duct, anterior mesonephric mesenchyme
      adjacent to somites exhibits greater competence to initiate tubular
      differentiation in response to Wnt signaling than more posterior mesonephric
      mesenchyme adjacent to unsegmented paraxial mesoderm. It is proposed that
      mesonephric tubule differentiation is regulated by two independent parallel
      waves, one of inductive signaling from the nephric duct and the other of
      competence of the mesonephric mesenchyme to undergo tubular differentiation, both
      of which travel from anterior to posterior in parallel with the formation of new
      somites. 

PMID- 24091142
TI  - Susceptibility to life-threatening ventricular arrhythmias in an animal model of
      paradoxical sleep deprivation.
AB  - BACKGROUND: According to some reports regarding the increase of cardiac events
      following sleep deprivation, our study was conducted to clarify the effects of
      rapid eye movement (REM) sleep deprivation on susceptibility to lethal
      ventricular arrhythmias in rat. METHODS: The animal groups included the control
      group; the sham 48 and sham 72 groups (without sleep deprivation); and the test
      48 and test 72 groups, who experienced REM sleep deprivation for 48h and 72h,
      respectively. For induction of cardiac arrhythmia, aconitine was infused via the
      tail vein of the animals. RESULTS: After 72h of REM sleep deprivation, the blood
      pressure (BP) levels and the QTc interval of the electrocardiogram (ECG) were
      significantly increased (P<.05 and P<.01, respectively). However, the sleep
      deprivation had no significant effect on the heart rate (HR), myocardial oxygen
      consumption index, and plasma corticosterone level. Furthermore, sleep
      deprivation increased the latency times of premature ventricular contraction
      (PVC), ventricular tachycardia (VT), and also the PVC number; however, it did not
      increase the number, duration, and severity of VT and ventricular fibrillation
      (VF). CONCLUSION: Our findings suggest that 72h of REM sleep deprivation is
      associated with increased risk for hypertension and QT interval prolongation
      under nonstressful conditions; however, it does not increase the susceptibility
      to lethal ventricular arrhythmia in rat.

PMID- 24091143
TI  - Nocturnal autonomic function in preschool children with sleep-disordered
      breathing.
AB  - BACKGROUND: Obstructive sleep apnea (OSA) is associated with autonomic
      dysfunction in adults and school-aged children; however, this association has not
      been investigated in preschool children. We aimed to analyze heart rate
      variability (HRV) and catecholamine levels in preschool children with OSA.
      METHODS: One hundred and forty-two snoring children aged 3-5years and 38
      nonsnoring control group children underwent overnight polysomnography (PSG).
      Nocturnal urinary catecholamines were measured in 120 children. Children were
      grouped according to their obstructive apnea-hypopnea index (OAHI) (control [no
      snoring], OAHI?1event/h; primary snoring, OAHI?1event/h; mild OSA
      OAHI>1?5events/h; moderate to severe [MS] OSA, OAHI>5events/h). The HRV
      parameters for each child were averaged during rapid eye movement (REM) and non
      REM (NREM) sleep. RESULTS: During stable sleep, low-frequency (LF) HRV was
      similar between groups. High-frequency (HF) HRV was higher in the MS OSA group
      compared with the control group during all sleep stages (NREM sleep stages 1 and
      2 [NREM1/2], 4234+/-523ms(2) vs 2604+/-457ms(2); NREM sleep stages 3 and 4
      [NREM3/4], 4152+/-741ms(2) vs 3035+/-647ms(2); REM, 1836+/-255ms(2) vs 1456+/
      292ms(2); P<.01 for all). The LF/HF ratio was lower in the MS OSA group compared
      with the control group (NREM1/2, 0.4+/-0.06 vs 0.7+/-0.05; NREM3/4, 0.3+/-0.06 vs
      0.4+/-0.05; REM, 0.8+/-0.1 vs 1.3+/-0.1; P<.01 for all). Catecholamine levels
      were not different between groups. CONCLUSIONS: In preschool children, OSA is
      associated with altered HRV, largely due to the HF fluctuations in heart rate
      (HR) which occur during respiratory events and are still evident during stable
      sleep. The preschool age may represent a window of opportunity for treatment of
      OSA before the onset of the severe autonomic dysfunction associated with OSA in
      adults and older children.

PMID- 24091144
TI  - Expression of LYN and PTEN genes in chronic myeloid leukemia and their importance
      in therapeutic strategy.
AB  - Tyrosine kinase inhibitors (TKIs), imatinib, nilotinib and dasatinib, are the
      current treatment of chronic myeloid leukemia (CML). BCR-ABL1 point mutations are
      the principal cause of resistance to treatment; however other mechanisms could be
      involved in failure to TKI therapy. LYN is a src kinase protein that regulates
      survival and responsiveness of tumor cells by a BCR-ABL1 independent mechanism.
      PTEN tumor suppressor gene is downregulated by BCR-ABL1 in CML stem cells and its
      deletion is associated with acceleration of disease. In this study we evaluated
      the expression of LYN, PTEN and the ratio of both genes in 40 healthy donors (HD)
      and in 139 CML patients; 88 of them resistant to TKI in different phases of
      disease and 51 in chronic phase classified as optimal responders (OR) to TKI [40
      treated with imatinib or nilotinib (OR-IN) and 11 treated with dasatinib (OR-D)
      therapy]. When we analyzed the gene expression values of LYN, an increase was
      observed only in advanced stages of the disease, however, when we analyzed the
      ratio between LYN and PTEN genes, the group of resistant patients in chronic
      phase in imatinib or nilotinib treatment (CP-IN) also showed a significant
      increase. Resistant patients treated with dasatinib, a src kinase inhibitor,
      presented a similar ratio to the observed in HD. In addition, the LYN/PTEN ratio
      and the LYN expression showed a direct significant correlation with BCR-ABL1
      transcript levels in unmutated resistant patients treated with non-src kinase
      inhibitors. We were able to identify 8/35 (23%) of cases in CP-IN and 4/12 (33%)
      in accelerated phase and blast phase (AP/BC-IN), in which resistance could be
      associated with an increase in the ratio of the LYN/PTEN. Our data suggest that
      the LYN/PTEN expression ratio may be a sensitive monitor of disease progression
      in unmutated CML patients under imatinib or nilotinib treatment. This ratio could
      detect cases when resistance is related to altered LYN expression, suggesting
      that the treatment change to a src kinase inhibitor would be most suitable to
      overcome resistance.

PMID- 24091145
TI  - Thalassemic osteopathy: a new marker of bone deposition.
AB  - Osteopathy represents a prominent cause of morbidity in patients with beta
      thalassemia major (TM) and manifests as osteopenia/osteoporosis. Biochemical
      turnover markers (BTMs) are considered a useful, non-invasive tool for the
      clinical follow-up of osteoporotic patients; they can provide a dynamic view of
      the remodeling process and give information on the metabolic activity of bone
      tissue as well as on the pathogenesis of bone loss. The amino-terminal pro
      peptide of type I procollagen (P1NP) is a recently introduced marker that is
      considered the most sensitive index of bone formation. Although demonstrated in
      several categories of patients with bone disease, there is little information on
      the clinical usefulness of this bone formation index in thalassemic patients. We
      evaluated the P1NP levels of 53 adult patients with b-thalassemia major (21 males
      and 32 females, mean age 34.5 +/- 5.7, range 22-46 years) and associated
      osteopathy. We investigated the correlation between P1NP and bone condition as
      examined by dual X-ray photon absorptiometry and with BTMs expressing bone
      resorption and bone mineralization (carboxyterminal collagen cross-linked (CTX)
      terminal regions of type I collagen and osteocalcin, respectively). P1NP serum
      levels were correlated with CTX levels (r=0.545, p<0.001); the results were
      unchanged when males and females, as well as osteoporotic and osteopenic
      subgroups, were considered separately. No correlation was demonstrated neither
      between OC and CTX (r=0.17, p=ns), nor between P1NP and OC levels (r=0.11, p=ns).
      No correlation was demonstrated among the P1NP/CTX ratio and age, OC or
      densitometric values and no difference was found in the same ratio between
      osteopenic (0.19 +/- 0.16) and osteoporotic (0.15 +/- 0.14) patients. Similar
      results were obtained for the OC/CTX ratio, as it was not correlated with age,
      P1NP or densitometric values. This is the first report of circulating P1NP in
      patients with TM-associated osteoporosis. P1NP and CTX assays show good precision
      and low analytical CV, and, compared to other markers, they can acceptably
      reflect bone metabolic processes and promptly respond to antiosteoporotic
      treatments. We trust that this sensitive marker can be useful in the assessment
      of treatment efficacy and can overcome the pitfalls due to wide variability in
      the normal values of most BTMs that create difficulty in pinpointing the
      individual patient's response.

PMID- 24091146
TI  - Preface to issue on embryonic and fetal hematopoiesis.

PMID- 24091147
TI  - [Discussion on Turkish scientific language and the accuracy of data].

PMID- 24091148
TI  - Physical forces exerted by microbubbles on a surface in a traveling wave field.
AB  - The effect of a wave with a varying traveling component on the bubble activity as
      well as the physical force generated by microbubbles on a surface has been
      studied. The acoustic emission from a collection of bubbles is measured in a 928
      kHz sound field. Particle removal tests on a surface, which actually measures the
      applied physical force by the bubbles on that surface, indicate a very strong
      dependence on the angle of incidence. In other words, when the traveling wave
      component is maximized, the average physical force applied by microbubbles
      reaches a maximum. Almost complete particle removal for 78 nm silica particles
      was obtained for a traveling wave, while particle removal efficiency was reduced
      to only a few percent when a standing wave was applied. This increase in particle
      removal for a traveling wave is probably caused by a decrease in bubble trapping
      at nodes and antinodes in a standing wave field.

PMID- 24091149
TI  - Application of an effective medium theory for modeling ultrasound wave
      propagation in healing long bones.
AB  - Quantitative ultrasound has recently drawn significant interest in the monitoring
      of the bone healing process. Several research groups have studied ultrasound
      propagation in healing bones numerically, assuming callus to be a homogeneous and
      isotropic medium, thus neglecting the multiple scattering phenomena that occur
      due to the porous nature of callus. In this study, we model ultrasound wave
      propagation in healing long bones using an iterative effective medium
      approximation (IEMA), which has been shown to be significantly accurate for
      highly concentrated elastic mixtures. First, the effectiveness of IEMA in bone
      characterization is examined: (a) by comparing the theoretical phase velocities
      with experimental measurements in cancellous bone mimicking phantoms, and (b) by
      simulating wave propagation in complex healing bone geometries by using IEMA. The
      original material properties of cortical bone and callus were derived using
      serial scanning acoustic microscopy (SAM) images from previous animal studies.
      Guided wave analysis is performed for different healing stages and the results
      clearly indicate that IEMA predictions could provide supplementary information
      for bone assessment during the healing process. This methodology could
      potentially be applied in numerical studies dealing with wave propagation in
      composite media such as healing or osteoporotic bones in order to reduce the
      simulation time and simplify the study of complicated geometries with a
      significant porous nature. 

PMID- 24091150
TI  - Characteristic model of travelling wave ultrasonic motor.
AB  - In general, the design and analysis of ultrasonic motor and motor's control
      strategy are based on mathematical model. The academic model is widely used in
      the analysis of traveling wave ultrasonic motor (TWUSM). But the dispersive
      characteristic of piezoelectric ceramics and other complicated process, such as
      the friction, make the model's precision not so accurate. On the other hand,
      identification modeling method, which is built based on the tested data, has
      obtained increasing application in the study of ultrasonic motor's control
      technology. Based on the identification model, many control strategies can be
      designed easily. But the identification model is an approximate model, so if a
      more accurate model of ultrasonic motor can be obtained, the analysis and design
      of motor control system will be more effective. Characteristic model is a kind of
      identification model which can accurately describe the characteristics of TWUSM.
      Based on the tested data, this paper proposes the modeling method of ultrasonic
      motor's characteristic model. The paper also makes a comparison of the
      effectiveness of different identification algorithms. Aiming at the speed control
      of ultrasonic motor, the influence of the parameter's initial values on the
      precision of model is discussed. The calculating results indicate the
      availability of this characteristic model. 

PMID- 24091151
TI  - Determining the quality of IMCI pneumonia care in Malawian children.
AB  - BACKGROUND: Although pneumonia is the leading cause of child mortality worldwide,
      little is known about the quality of routine pneumonia care in high burden
      settings like Malawi that utilize World Health Organization's Integrated
      Management of Childhood Illnesses (IMCI) guidelines. Due to severe human resource
      constraints, the majority of clinical care in Malawi is delivered by non
      physician clinicians called Clinical Officers (COs). AIM: To assess the quality
      of child pneumonia care delivered by Malawian COs in routine care conditions.
      METHODS: At an outpatient district-level clinic in Lilongwe, Malawi, 10 COs
      caring for 695 children who presented with fever, cough, or difficulty breathing
      were compared to IMCI pneumonia diagnostic and treatment guidelines. RESULTS:
      Fewer than 1% of patients received an evaluation by COs that included all 16
      elements of the history and physical examination. The respiratory rate was only
      determined in 16.1% of patients presenting with cough or difficulty breathing. Of
      the 274 children with IMCI-defined pneumonia, COs correctly diagnosed 30%, and
      administered correct pneumonia care in less than 25%. COs failed to hospitalize
      40.8% of children with severe or very severe pneumonia. CONCLUSIONS: IMCI
      pneumonia care quality at this Malawian government clinic is alarmingly low.
      Along with reassessing current pneumonia training and supervision approaches,
      novel quality improvement interventions are necessary to improve care.

PMID- 24091152
TI  - Asaia accelerates larval development of Anopheles gambiae.
AB  - Arthropod borne diseases cause significant human morbidity and mortality and,
      therefore, efficient measures to control transmission of the disease agents would
      have great impact on human health. One strategy to achieve this goal is based on
      the manipulation of bacterial symbionts of vectors. Bacteria of the Gram
      negative, acetic acid bacterium genus Asaia have been found to be stably
      associated with larvae and adults of the Southeast Asian malaria vector Anopheles
      stephensi, dominating the microbiota of the mosquito. We show here that after the
      infection of Anopheles gambiae larvae with Asaia the bacteria were stably
      associated with the mosquitoes, becoming part of the microflora of the midgut and
      remaining there for the duration of the life cycle. Moreover they were passed on
      to the next generation through vertical transmission. Additionally, we show that
      there is an increase in the developmental rate when additional bacteria are
      introduced into the organism which leads us to the conclusion that Asaia plays a
      yet undetermined crucial role during the larval stages. Our microarray analysis
      showed that the larval genes that are mostly affected are involved in cuticle
      formation, and include mainly members of the CPR gene family. 

PMID- 24091153
TI  - Multifunctional nanomedicine platform for concurrent delivery of chemotherapeutic
      drugs and mild hyperthermia to ovarian cancer cells.
AB  - A multifunctional tumor-targeting delivery system was developed and evaluated for
      an efficient treatment of drug-resistant ovarian cancer by combinatorial
      therapeutic modality based on chemotherapy and mild hyperthermia. The engineered
      iron oxide nanoparticle (IONPs)-based nanocarrier served as an efficient delivery
      vehicle for doxorubicin and provided the ability to heat cancer cells remotely
      upon exposure to an alternating magnetic field (AMF). The nanocarrier was
      additionally modified with polyethylene glycol and LHRH peptide to improve its
      biocompatibility and ability to target tumor cells. The synthesized delivery
      system has an average size of 97.1 nm and a zeta potential close to zero, both
      parameters favorable for increased stability in biological media and decreased
      elimination by the immune system. The nanocarrier demonstrated faster drug
      release in acidic conditions that mimic the tumor environment. It was also
      observed that the LHRH targeted delivery system could effectively enter drug
      resistant ovarian cancer cells, and the fate of doxorubicin was tracked with
      fluorescence microscope. Mild hyperthermia (40 degrees C) generated by IONPs
      under exposure to AMF synergistically increased the cytotoxicity of doxorubicin
      delivered by the developed nanocarrier to cancer cells. Thus, the developed IONPs
      based delivery system has high potential in the effective treatment of ovarian
      cancer by combinatorial approach.

PMID- 24091154
TI  - Response to the comment on "partitioning of polar and non-polar neutral organic
      chemicals into human and cow milk".

PMID- 24091155
TI  - Characterization of extended-spectrum beta-lactamase-producing Klebsiella
      pneumoniae from Riyadh, Saudi Arabia.
AB  - The objectives of this study were to determine the prevalences, genotypes, and
      clonal relationships of extended-spectrum beta-lactamase (ESBL)-producing strains
      in 98 Klebsiella pneumoniae isolates from Riyadh. The prevalence of ESBLs in
      these strains was 37.75%. All isolates that were confirmed to have ESBLs were
      completely resistant to amoxicillin/clavulanate, aztreonam, cefotaxime,
      ceftazidime, cefoxitin, and gentamicin and were susceptible to tigecycline,
      colistin, and imipenem. In total, 16.6, 77, and 91.6% of isolates were resistant
      to amikacin, ciprofloxacin, and piperacillin/tazobactam, respectively. The
      prevalences of isolates producing the beta-lactamases SHV, CTX-M, and TEM were
      91.9, 86.5, and 54.05%, respectively. The most frequent ESBL gene detected was
      blaCTX-M-15, which was observed in 75% of isolates. Other frequent ESBL genes
      were blaSHV-12 (29.73% of isolates) and blaSHV-5 (5.4% of isolates);
      additionally, blaCTX-M-3, blaCTX-M-27, blaCTX-M-57, and blaCTX-M-82 were each
      detected in one isolate. Pulsed-field gel electrophoresis (PFGE) analysis
      revealed the presence of diverse and unrelated clones. The high prevalence of
      ESBL producers among the strains examined in our study was not due to the spread
      of a single clone of bacteria. Clone A was detected in six isolates, indicating
      intra-hospital spread. Our study documented a high prevalence of the CTX-M-15
      product in K. pneumoniae and demonstrated that SHV-12 was also highly prevalent.
      This study represents the first report of CTX-M-3, CTX-M-27, CTX-M-57, and CTX-M
      82 beta-lactamases in K. pneumoniae isolates from Saudi Arabia. 

PMID- 24091156
TI  - Releasing the brake: restoring fast axonal transport in neurodegenerative
      disorders.
AB  - Emerging evidence suggests that the dysregulation of fast axonal transport (FAT)
      plays a crucial role in several neurodegenerative disorders. Some of these
      diseases are caused by mutations affecting the molecular motors or adaptors that
      mediate FAT, and transport defects in organelles such as mitochondria and
      vesicles are observed in most, if not all neurodegenerative disorders. The
      relationship between neurodegenerative disorders and FAT is probably due to the
      extreme polarization of neurons, which extend long processes such as axons and
      dendrites. These characteristics render neurons particularly sensitive to
      transport alterations. Here we review the impact of such alterations on neuronal
      survival. We also discuss various strategies that might restore FAT, potentially
      slowing disease progression. 

PMID- 24091157
TI  - Toward full economic valuation of forest fuels-reduction treatments.
AB  - Our goal was to move toward full economic valuation of fuels-reduction treatments
      applied to ponderosa pine (Pinus ponderosa) forests. For each of five fuels
      reduction projects in northern Arizona, we calculated the economic value of
      carbon storage and carbon releases over one century produced by two fuels
      reduction treatments of thinning following by prescribed burning every one (Rx10)
      or two (Rx20) decades and for no treatment followed by intense wildfire once in
      the first 50 years (HF50) or once in the first 100 years (HF100). Our estimates
      include two uses of harvested wood, the current use as pallets, and multiproduct
      use as paper, pallets, and construction materials. Additionally, we included the
      economic value of damage and loss from wildfire. Results indicate that treatments
      increase carbon stock in live trees over time; however, the inclusion of carbon
      emissions from treatments reduces net carbon storage and thereby carbon credits
      and revenue. The economic valuation shows that the highest net benefit of
      $5029.74 ha(-1) occurs for the Rx20 treatment with the HF50 baseline and the high
      estimated treatment benefits of avoided losses, regional economic benefits, and
      community value of fire risk reduction. The lowest net benefit of -$3458.02 ha(
      1) occurs for the Rx10 treatment with the HF100 baseline and the low estimated
      treatment benefits. We conclude that current nonmarket values such as avoided
      wildfire damage should be included with values of traditional wood products and
      emerging values of carbon storage to more appropriately estimate long-term
      benefits and costs of forest fuels-reduction treatments. 

PMID- 24091158
TI  - Accounting protesting and warm glow bidding in Contingent Valuation surveys
      considering the management of environmental goods--an empirical case study
      assessing the value of protecting a Natura 2000 wetland area in Greece.
AB  - Based on a Contingent Valuation survey aiming to reveal the willingness to pay
      (WTP) for conservation of a wetland area in Greece, we show how protest and warm
      glow motives can be taken into account when modeling WTP. In a sample of more
      than 300 respondents, we find that 54% of the positive bids are rooted to some
      extent in warm glow reasoning while 29% of the zero bids can be classified as
      expressions of protest rather than preferences. In previous studies, warm glow
      bidders are only rarely identified while protesters are typically identified and
      excluded from further analysis. We test for selection bias associated with simple
      removal of both protesters and warm glow bidders in our data. Our findings show
      that removal of warm glow bidders does not significantly distort WTP whereas we
      find strong evidence of selection bias associated with removal of protesters. We
      show how to correct for such selection bias by using a sample selection model. In
      our empirical sample, using the typical approach of removing protesters from the
      analysis, the value of protecting the wetland is significantly underestimated by
      as much as 46% unless correcting for selection bias. 

PMID- 24091159
TI  - Environmental impact associated with activated carbon preparation from olive
      waste cake via life cycle assessment.
AB  - The life cycle assessment (LCA) environmental tool was implemented to quantify
      the potential environmental impacts associated with the activated carbon (AC)
      production process from olive-waste cakes in Tunisia. On the basis of laboratory
      investigations for AC preparation, a flowchart was developed and the
      environmental impacts were determined. The LCA functional unit chosen was the
      production of 1 kg of AC from by-product olive-waste cakes. The results showed
      that impregnation using H3PO4 presented the highest environmental impacts for the
      majority of the indicators tested: acidification potential (62%), eutrophication
      (96%), ozone depletion potential (44%), human toxicity (64%), fresh water aquatic
      ecotoxicity (90%) and terrestrial ecotoxicity (92%). One of the highest impacts
      was found to be the global warming potential (11.096 kg CO2 eq/kg AC), which was
      equally weighted between the steps involving impregnation, pyrolysis, and drying
      the washed AC. The cumulative energy demand of the AC production process from the
      by-product olive-waste cakes was 167.63 MJ contributed by impregnation,
      pyrolysis, and drying the washed AC steps. The use of phosphoric acid and
      electricity in the AC production were the main factors responsible for the
      majority of the impacts. If certain modifications are incorporated into the AC
      production, such as implementing synthesis gas recovery and reusing it as an
      energy source and recovery of phosphoric acid after AC washing, additional
      savings could be realized, and environmental impacts could be minimized. 

PMID- 24091160
TI  - Time-lapse observation of the dedifferentiation process in mouse chondrocytes
      using chondrocyte-specific reporters.
AB  - OBJECTIVE: When chondrocytes prepared from cartilage are expanded in monolayer
      culture, fibroblast-like cells gradually prevail. Although these prevailing
      fibroblast-like cells are believed to emerge because of the dedifferentiation of
      chondrocytes, the definite origin of the prevailing fibroblast-like cells has not
      been determined. We herein examined whether the prevailing non-chondrocytic cells
      observed after monolayer expansion culture arise from dedifferentiating
      chondrocytes or are the result of the overgrowth of fibroblasts that are present
      at the start of the culture. We also evaluated whether chondrocytes
      dedifferentiate because they proliferate or because they are cultured in
      monolayers. METHODS: Chondrocytes were prepared from Col11a2-EGFP transgenic mice
      and Col11a2-Cre; R26-stop(flox)-EYFP transgenic mice, which respectively express
      enhanced green fluorescent protein (EGFP) and Cre specifically in chondrocytes
      under the control of Col11a2 promoter/enhancer sequences. Col11a2-Cre; R26
      stop(flox)-EYFP mice express enhanced yellow fluorescent protein (EYFP) only in
      cells which express or used to express Cre. We performed a time-lapse observation
      of the chondrocytes during monolayer expansion culture, and also observed the
      chondrocytes after treatment with mitomycin C. RESULTS: A time-lapse observation
      showed that Col11a2-EGFP chondrocytes underwent cell divisions, lost GFP
      fluorescence, increased cell numbers, and prevailed during the expansion culture.
      The observation of the Col11a2-Cre; R26-stop(flox)-EYFP chondrocytes confirmed
      that most of the cells after expansion in monolayer culture had been
      chondrocytes. Mitotically inactive chondrocytes generated by treatment with
      mitomycin C still underwent dedifferentiation, thus suggesting that chondrocyte
      dedifferentiation is not associated with cell division. CONCLUSION: The non
      chondrocytic cells that prevail after the monolayer expansion culture of
      chondrocytes originate from chondrocytes, and are not generated by the overgrowth
      of fibroblasts that are present at the start of the culture. Chondrocyte
      dedifferentiation does not appear to be associated with cell division.

PMID- 24091161
TI  - Differences between X-ray and MRI-determined knee cartilage thickness in weight
      bearing and non-weight-bearing conditions.
AB  - OBJECTIVE: Determine the effect of loading upon MRI-based mean medial
      femorotibial cartilage thickness (mMFT_th) and radiograph-based minimum joint
      space width (mJSW), and determine loading's effect on the relationship between
      these measures. METHODS: MRI and radiographs were analyzed of 25 knees in weight
      bearing and non-weight-bearing conditions. Eight subjects had a Kellgren-Lawrence
      (KL) grade of 0, indicating no evidence of radiographic OA. The rest were KL = 2
      or KL = 3, indicating mild to moderate OA. The change from unloaded to loaded
      conditions was calculated. RESULTS: Joint space measures decreased from unloaded
      to loaded conditions for both radiographs (mJSW = 3.29 mm unloaded to 3.16 mm
      loaded, P < 0.05) and MRI (mMFT_th = 2.70 mm unloaded to 2.55 mm loaded P <
      0.001). The mean absolute difference measured from radiographs was larger for the
      OA group than the control group, at -0.20 mm for OA vs +0.01 mm for control.
      Loaded X-ray and loaded MRI joint space values from our study were no better
      correlated to one another than loaded X-ray and unloaded MRI. CONCLUSION: Knee
      loading does not add a very significant value to the study of joint space on
      healthy knees, but loading may play a role in the study of OA knees. Unloaded MRI
      assessments of cartilage thickness are as correlated to loaded JSW as to loaded
      MRI measurements. More study is necessary to determine whether loaded MRI adds
      significant value to the study of OA progression.

PMID- 24091162
TI  - Negative depletion of alpha/beta+ T cells and of CD19+ B lymphocytes: a novel
      frontier to optimize the effect of innate immunity in HLA-mismatched
      hematopoietic stem cell transplantation.
AB  - In recent years, infusion of T-cell depleted hematopoietic stem cells from an HLA
      haploidentical relative has been shown to represent a suitable and effective,
      alternative option in patients in need of an allograft who lack an HLA-identical
      relative. In particular, this type of allograft is associated with the enormous
      advantage of offering an immediate transplant treatment to virtually all
      pediatric patients without an HLA-matched donor, whether related or unrelated, or
      a suitable umbilical cord blood unit. Several studies have shown that in patients
      given a T-cell depleted transplant relevant part of the anti-leukemia effect is
      mediated by alloreactive (i.e. KIR/HLA mismatched) Natural Killer cells
      originated from donor hematopoietic stem cells. After infusion of positively
      selected hematopoietic stem cell, fully functioning Natural Killer cells emerge
      in the recipient peripheral blood, persisting over time, only several weeks after
      the allograft. We have developed a new method of T-cell depletion (based on the
      physical elimination of mature T cells carrying alpha and beta chains of the T
      cell receptor), which permits to maintain mature donor-derived alloreactive
      Natural Killer cells and gammadelta(+) T cells in the graft. We, thus, started a
      formal study in children with hematological disorders aimed at evaluating the
      safety and efficacy of this approach. Preliminary results on 60 children
      transplanted so far after this type of graft manipulation are particularly
      promising. 

PMID- 24091163
TI  - The time course of temporal preparation in an applied setting: a study of gaming
      behavior.
AB  - We examined the time course of temporal preparation in the practice of computer
      gaming. Participants held an infrared rifle to shoot animated figures
      ("terrorists") that appeared from an elevator that opened briefly after the sound
      of a bell. The sound was either loud or soft and the interval between the sound
      and the opening of the elevator varied between 100 and 600ms. We found that
      shooting latency decreased exponentially as a function of interval, reflecting
      growing temporal preparation towards an optimum. When the sound was soft, this
      function was shifted to the right as compared to when the sound was loud. These
      findings are consistent with a model assuming that preparation starts upon the
      detection of a warning (i.e., later for the soft than for the loud sound) and
      continues until the detection of a target (i.e., longer as the interval
      increases). These results signify a successful application of a theoretical model
      in an applied setting. 

PMID- 24091165
TI  - Abstracts of the annual meeting of the hungarian society for microbiology.

PMID- 24091164
TI  - Drug attitude and other predictors of medication adherence in schizophrenia: 12
      months of electronic monitoring (MEMS((r))) in the Swedish COAST-study.
AB  - The aim was to investigate clinical predictors of adherence to antipsychotics.
      Medication use was electronically monitored with a Medication Event Monitoring
      System (MEMS((r))) for 12 months in 112 outpatients with schizophrenia and
      schizophrenia-like psychosis according to DSM-IV. Symptom burden, insight,
      psychosocial function (PSP) and side effects were rated at baseline. A
      comprehensive neuropsychological test battery was administered and a global
      composite score was calculated. The Drug Attitude Inventory (DAI-10) was filled
      in. A slightly modified DAI-10 version for informants was distributed as a postal
      questionnaire. Non-adherence (MEMS((r)) adherence <=0.80) was observed in 27%. In
      univariate regression models low scores on DAI-10 and DAI-10 informant, higher
      positive symptom burden, poor function, psychiatric side effects and lack of
      insight predicted non-adherence. No association was observed with global
      cognitive function. In multivariate regression models, low patient-rated DAI-10
      and PSP scores emerged as predictors of non-adherence. A ROC analysis showed that
      DAI-10 had a moderate ability to correctly identify non-adherent patients
      (AUC=0.73, p<0.001). At the most "optimal" cut-off of 4, one-third of the
      adherent would falsely be identified as non-adherent. A somewhat larger AUC
      (0.78, p<0.001) was observed when the ROC procedure was applied to the final
      regression model including DAI-10 and PSP. For the subgroup with informant data,
      the AUC for the DAI-10 informant version was 0.68 (p=0.021). Non-adherence cannot
      be properly predicted in the clinical setting on the basis of these instruments
      alone. The DAI-10 informant questionnaire needs further testing. 

PMID- 24091166
TI  - Effectiveness of inhaled tobramycin in eradicating Pseudomonas aeruginosa in
      children with cystic fibrosis.
AB  - BACKGROUND: Inhaled tobramycin therapy has been shown to be efficacious in
      clinical trials for the eradication of initial Pseudomonas aeruginosa infection
      in children with cystic fibrosis (CF). However, the effectiveness of different
      regimens in eradicating P. aeruginosa and preventing the development of chronic
      infection in actual clinical settings has yet to be determined. METHODS: This was
      an observational study of children (<18 years of age) with CF with incident P.
      aeruginosa infection from 2005-2012 based on data collected from the Toronto CF
      Database and medical charts. Patients who received inhaled tobramycin (80 mg/2 ml
      twice daily for 365 days) were compared to those who received tobramycin
      inhalation solution (TIS) (300 mg/5 ml twice daily for 28 days) with respect to
      eradication and development of chronic infection. We also examined the risk
      factors for recurrence of infection. RESULTS: During the study period, 65
      patients were identified with incident P. aeruginosa, of which 7 (11%) failed
      eradication therapy. Eradication failure was similar between the two treatment
      groups. A total of 4 patients (6%) developed chronic P. aeruginosa infection in
      the 12 months following the end of therapy with no differences between treatment
      groups. Female gender, older age, pancreatic insufficiency, lower lung function
      and worse nutritional status were identified as risk factors for recurrence of P.
      aeruginosa infection. CONCLUSIONS: Both regimens of inhaled tobramycin have
      similar effectiveness in eradicating P. aeruginosa and preventing chronic P.
      aeruginosa infection in CF patients in clinical practice. Further work is needed,
      however, to identify patient characteristics and bacterial factors that play a
      role in eradication failure, in order to develop more effective antimicrobial
      rescue treatment strategies.

PMID- 24091167
TI  - Annual Review Clinic improves care in children with cystic fibrosis.
AB  - BACKGROUND: It is unclear whether annual multidisciplinary reviews in cystic
      fibrosis (CF) patients should be conducted in dedicated annual review (AR)
      clinics or during continuous assessments throughout the year. Our aim was to
      assess the effect of introducing an AR clinic. METHODS: A retrospective written
      and electronic record review of CF patients was carried out for 2007 (no AR
      Clinic) and 2010 (established AR Clinic) calendar years. An internet-based
      satisfaction survey was distributed to families attending the AR clinic. RESULTS:
      In total, 123 children (mean age 9.5 years, range 1.32-18.8 years) and 141
      children (8.3 years, 1.1-18.3 years) were included in 2007 and 2010 respectively.
      There was a significant increase in multidisciplinary reviews (documented annual
      review 28% vs 85%, P < 0.001; dietary assessment 46% vs 92%, P < 0.001) and
      investigations (OGTT 2% vs 74%, P < 0.001; abdominal ultrasound 35% vs 85%, P <
      0.001) conducted after the introduction of AR clinic. The majority of the
      families surveyed (85%) were satisfied or very satisfied with the AR clinic.
      CONCLUSIONS: CF AR clinic significantly improves the number of annual
      investigations and multidisciplinary reviews performed. Families were satisfied
      with this new process.

PMID- 24091168
TI  - Hydrogen peroxide modulates phenylephrine-induced contractile response in renal
      hypertensive rat aorta.
AB  - Endothelium-derived factors play an important role in vascular tone control. This
      study aimed to evaluate how endothelium and reactive oxygen species (ROS)
      contribute to phenylephrine (PE)-induced contraction in renovascular hypertensive
      (2K-1C) and normotensive (2K) rats aortas. The effects of the superoxide
      scavenger Tiron (0.1mM and 1mM) or catalase (30 U/ml, 90 U/ml, 150 U/ml and 300
      U/ml) on the PE-induced contraction were evaluated in both intact endothelium
      (E+) and denuded (E-) aortas. Endothelium removal increased the PE-induced
      contractions. The maximum contractile response decreased only in 2K-1C rat E+
      aorta, and catalase (30 U/ml, 90 U/ml, 150 U/ml) partially reversed this effect.
      Endothelium increased the basal hydrogen peroxide (H2O2) production in 2K and 2K
      1C rats aortas. PE-stimulated H2O2 production was higher in 2K-1C (E+/E-) than in
      2K (E+/E-). Inhibition of the enzymes cyclooxygenase, NADPH-oxidase, xanthine
      oxidase, and superoxide dismutase reduced the PE-stimulated H2O2 production in 2K
      1C rat aorta. The decreased contraction to PE in 2K-1C rat aorta is partially due
      to endothelial H2O2 production; however, in denuded aorta, it contributes to
      maintaining the contractile response. Superoxide plays an important role on the
      PE-induced contraction in 2K rat denuded aorta, whereas in 2K-1C rat aorta, it is
      H2O2 that plays an important role in this effect.

PMID- 24091169
TI  - Co-expression of the human cannabinoid receptor coding region splice variants
      (hCB1) affects the function of hCB1 receptor complexes.
AB  - The human type 1 cannabinoid (hCB1) receptor is expressed at high levels in the
      central nervous system. mRNA variants of the coding region of this receptor,
      human cannabinoid hCB1a and hCB1b receptors, have been identified, their
      biological function remains unclear. The present study demonstrated that the
      three human cannabinoid hCB1 coding region variants are expressed in the human
      and monkey (Macaca fascicularis) brain. Western blot analyses of homogenates from
      different regions of the monkey brain demonstrated that proteins with the
      expected molecular weights of the cannabinoid CB1, CB1a and CB1b receptors were
      co-expressed throughout the brain. Given the co-localization of these receptors,
      we hypothesized that physical interactions between the three splice variants may
      affect cannabinoid pharmacology. The human cannabinoid hCB1, hCB1a, and hCB1b
      receptors formed homodimers and heterodimers, as determined by BRET in
      transiently transfected HEK 293A cells. We found that the co-expression of the
      human cannabinoid hCB1 and each of the splice variants increased cell surface
      expression of the human cannabinoid hCB1 receptor and increased Gi/o-dependent
      ERK phosphorylation in response to cannabinoid agonists. Therefore, the human
      cannabinoid hCB1 coding region splice variants play an important physiological
      role in the activity of the endocannabinoid system. 

PMID- 24091170
TI  - Search and rescue in the Intermountain West states.
AB  - BACKGROUND: Minimal data exist regarding the activity, membership, training, and
      medical oversight of search and rescue (SAR) teams. OBJECTIVE: Our objective was
      to describe these characteristics in the Intermountain West SAR organizations.
      METHODS: A contact list was generated and electronic surveys were sent to SAR
      officials in each Intermountain West county. Results were descriptively analyzed.
      RESULTS: Of the contacted jurisdictions, 56% (156) responded to the survey. The
      annual average call volume was 29 missions (range, 5 to 152). Multiple levels of
      medical training were represented on SAR teams, ranging from first
      aid/cardiopulmonary resuscitation providers to the physician level, and 79% of
      teams provided some medical training to their membership. Of the SAR medical
      professionals, 23% had formal wilderness medical training. Local emergency
      medical services provided 60% of the medical care on SAR missions rather than SAR
      personnel. Formal physician medical oversight was present in 41% of the SAR
      teams. These physicians participated in a range of SAR activities including
      medical protocol drafting (including expanded scope of practice), medical
      trainings, mission participation, medical consultation, and prescribing
      medications for field use. The majority (69%) of those physicians were trained in
      emergency medicine, and 45% of the active medical directors had protocols
      allowing for an expanded scope of practice due to the remote nature of SAR
      medical care. CONCLUSIONS: Intermountain West SAR teams vary in their activity,
      composition, training, and level of medical oversight. This study confirms that
      opportunities exist for physician integration with SAR teams in the studied
      states and likely throughout the United States.

PMID- 24091171
TI  - Lung cancer in pregnancy: report of nine cases from an international
      collaborative study.
AB  - OBJECTIVE: Lung cancer is an uncommon diagnosis during pregnancy. The combination
      of smoking in young women, increased maternal age during pregnancy, and
      increasing incidence of lung cancer worldwide may cause an increase of pregnancy
      associated lung cancer. The aim of this study was to describe all cases of lung
      cancer during pregnancy, registered in the international Cancer in Pregnancy
      registration study (CIP study; www.cancerinpregnancy.org). MATERIALS AND METHODS:
      We present nine cases, all advanced lung cancer during the course of pregnancy.
      Collected data included demographic features of the study patients, cancer
      treatment, pregnancy outcome as well as maternal and fetal outcomes. RESULTS AND
      CONCLUSION: Nine pregnant patients from 4 European centres with a median age of
      33 years old (range, 26-42) were included. The median gestational age at
      diagnosis was 17 weeks (range, 6-28). All patients presented with metastatic
      disease including bone, lung, brain, spinal cord, pleura, lymph nodes, adrenal
      and liver. Histopathology was compatible with adenocarcinoma in 4 patients, non
      small cell lung cancer with unidentified subtype in 2 patients and squamous-cell,
      large-cell and a poorly differentiated carcinoma in 3 patients, respectively.
      Eight patients were treated with systemic therapy, five of them during gestation.
      No responses were seen. The maternal postpartum outcome was poor with less than
      one year survival following delivery. One patient experienced a spontaneous
      abortion and three pregnancies were terminated. Five infants were all born
      premature due to poor maternal status by cesarean section, with a median
      gestational age of 30 weeks (range 26-33). To summarize, lung cancer in pregnancy
      has a dismal maternal outcome in our series. We add nine new cases and discuss
      both therapeutic and prognostic results.

PMID- 24091172
TI  - Coadministration of low-dose serotonin/noradrenaline reuptake inhibitor (SNRI)
      duloxetine with alpha 2-adrenoceptor blockers to treat both female and male mild
      to-moderate stress urinary incontinence (SUI).
AB  - BACKGROUND: Female urinary incontinence is a relatively common disorder affecting
      women in different age groups, with significant prevalence amounts of stress
      related subtype (stress urinary incontinence, SUI). Various
      neurotransmitters/neuromodulators - particularly both the glutamatergic and GABA
      ergic ones - are involved in micturition/urinary continence nerve centre-based
      control, where Onuf's nucleus plays an important functional role under the
      adiuvant serotoninergic/ noradrenergic influences. OBJECTIVES: To outline,
      deriving them from the literature review, the SUI therapeutic implications of
      SNRI (serotonin-noradrenaline reuptake inhibitors) particularly of the
      duloxetine, though displaying its full therapeutic dose (40 mg twice/day)-related
      side effects and, therefore, highlighting recent issues concerning novel drug
      administration modalities to avoid such adverse events. EMERGING KNOWLEDGES:
      Intriguing studies in SUI animal models have shown that co-administration of
      duloxetine low dose with alpha 2-adrenoceptor antagonists - given the alpha 2
      adrenoceptor inhibition-induced enhancement of duloxetine effectiveness on the
      urethral rhabdospincter-can avoid the duloxetine-related adverse events though
      perspectively reaching, in perspective translational clinical applications, the
      awaited beneficial effects for women suffering from intrinsic rhabdosphincter
      deficiency-based mild-to-moderate SUI as well as, in men, to treat post
      prostatectomy mild SUI.

PMID- 24091173
TI  - Repair of the inguinal hernia using the hernia sac to correct the abdominal wall
      defect.
AB  - Surgery of the inguinal hernia is a challenge for the great incidence of
      recurrences. The aim of this study is demonstrate the usefulness of hernia sac in
      the repair of inguinal hernia. In 200 patients the hernia sac was used to
      reinforce the abdominal wall. The patients have been observed two years along and
      still now few recurrences (20%) have been observed. The hernia sac can be used to
      repair the inguinal hernia because it's a patient's tissue with no inflammation
      and rejection. 

PMID- 24091174
TI  - Health technology assessment and thyroid surgery.
AB  - The growth of technological innovation, the request for assistance, the rising
      patient's expectations and the interest of the industry have led to a rise in the
      cost of health care systems. In this context the role of the National Health
      System is not to delay the development or adoption of new technologies, but
      rather to drive the development selecting priorities and promoting its use.
      Health Technology Assessment (HTA) is a multidisciplinary and multidimensional
      approach for analyzing the medical-clinical, social, organizational, economic,
      ethical and legal implications of a technology (devices, drugs, procedures)
      through the assessment of multiple parameters such as effectiveness, safety,
      costs of the social and organizational impact. A health technology assessment is
      a comprehensive, systematic evaluation of the prerequisites for estimating the
      consequences of using health technology. Main characteristic of HTA is that the
      problem is tackled using an approach focused on four main elements: - technology;
      - patient; - organization; - economy. The authors have applied the HTA method for
      the analysis of the ultrasonic focus dissector on thyroid surgery. They compared
      the cost of the surgical procedure using the ultrasonic dissector and without it
      in a case study of 440 patients who underwent thyroidectomy. 

PMID- 24091176
TI  - Anatomical study of the intrahepatic biliary ducts. Parameters that guide the
      surgical approach in transplanting the left lobe of the liver.
AB  - INTRODUCTION: The techniques of split liver transplantation and transplanting
      organs from living donors require a thorough anatomical knowledge of biliary
      drainage, and this is an important factor in preventing complications. METHODS:
      forty-five human livers were used to perform this study. Measurements were made
      between the confluence of the right hepatic duct (RHD) and the left hepatic duct
      (LHD) and among the following structures: the venous ligament, the vertex of the
      confluence of the duct of segment II (DSll) and the duct of segment III (DSIII),
      the insertion of the duct of the segment I (DSI) and the duct of segment IV
      (DSIV). Then the distance between the vertex of the confluence of DSII and DSIII
      and the ligamentum venosum was checked. RESULTS: The LHD had less anatomical
      variation than the RHD. Four drainage patterns were established for the left
      lobe, and pattern l, in which the confluence of DSll and DSIII is to the left of
      the ligamentum venosum, is considered to be the most constant one. A single duct
      of the confluence of DSll and DSIII was found 1, 2 and 2.5 cm to the right of the
      ligamentum venosum in 65%, 80%, and 95% of the cases, respectively. CONCLUSION:
      It was possible to show evidence of four drainage patterns of the left anatomical
      lobe of the liver. Furthermore, it was possible to establish the ligamentum
      venosum as an anatomical reference for locating the confluences of the ducts of
      the left liver segments.

PMID- 24091175
TI  - Alterations in homeostasis after open surgery. A prospective randomized study.
AB  - INTRODUCTION: Alterations in homeostasis, and a subsequent increased risk for
      postoperative thromboembolic complications, are observed as a result of open
      surgery. Additionally, the stress response to surgical trauma precipitates a
      transient hypercoagulable state as well as inflammation. This study was conducted
      to evaluate the patterns in postoperative alterations of blood coagulation, and
      to detect their correlations with inflammatory markers. PATIENTS AND METHODS: The
      study included 50 patients with comparable demographic data, who were randomly
      assigned to undergo abdominal surgery. No previous coagulation disorders were
      noted. Blood samples were collected preoperatively and 72 h postoperatively. The
      following parameters were measured: prothrombin time (PT) and activated partial
      thromboplastin time (APTT); fibrinogen (FIB), D-dimer (D-D), and C-reactive
      protein (CRP) levels; and platelet (PLT) count. Prophylactic doses of low
      molecular weight heparin were administered to all patients. RESULTS: The PT mean
      value significantly changed from 90.38% before surgery to 81.25% after surgery.
      No statistical difference was observed between APTT values before and after
      surgery. FIB levels significantly increased from 381.50 mg/dL preoperatively to
      462.57 mg/dL postoperatively. Mean D-D levels also significantly increased from
      235.54 MUg/L preoperatively to 803.59 MUg/L postoperatively. PLT count
      significantly declined after surgery. Mean CRP levels significantly increased
      from 12.33 mg/L preoperatively to 44.28 mg/L postoperatively. A strong
      correlation was observed between D-D and C-RP levels after surgery. CONCLUSION:
      These results indicate that, despite administering antithromboembolic
      prophylaxis, a hypercoagulable state was observed following surgery. This state
      was enhanced by inflammation.

PMID- 24091177
TI  - Single-incision laparoscopic appendectomy is comparable to conventional
      laparoscopic and laparotomic appendectomy: our single center single surgeon
      experience.
AB  - Several studies have demonstrated the clinical and technical benefits of the
      laparoscopic surgery for complicated and uncomplicated appendicitis. Our
      retrospective study included 12 patient who underwent SILS appendectomy (SILS-A),
      14 who received conventional laparoscopic surgery (VL-A), and 12 who received
      laparotomic appendectomy (OA); performed in all cases by the same surgeon (C.F.).
      The aim of this study was the comparison between this three different surgical
      techniques on same features: post operative leukocytosis, post operative pain,
      need abdominal drainage, esthetic viewpoint, incidence of complication, hospital
      stay. The results showed no significant differences between SILS-A and VLS-A,
      while an evident improvement shows versus O-A, even though not statistically
      significative. SILS was more effective in decreasing the risk of postoperative
      wound infection. 

PMID- 24091178
TI  - Laparoscopic treatment for esophageal achalasia: experience at a single center.
AB  - BACKGROUND: Achalasia is a not frequent esophageal disorder characterized by the
      absence of esophageal peristalsis and incomplete relaxation of the lower
      esophageal sphincter (LES). Its cause is unknown. The aim of treatment is to
      improve the symptoms. We report the results of the treatment of this condition
      achieved in one center. PATIENTS AND METHODS: We conducted a retrospective study
      of patients with esophageal achalasia. In the period 2010-2012 we observed 64
      patients, of whom 19 were referred for medical treatment. Three of the remaining
      patients underwent botulinum toxin injection, 17 underwent multiple endoscopic
      dilation procedures and 25 underwent laparoscopic surgery. RESULTS: There were no
      complications in the group undergoing endoscopic therapy, but symptom remission
      was only temporary. Patients undergoing surgery showed a significant improvement
      in symptoms and no recurrence throughout the follow-up period, that is still
      ongoing (3 years). There were no major complications in any case and no morbidity
      or mortality. CONCLUSIONS: Surgical treatment of esophageal achalasia with
      laparoscopic Heller myotomy and Dor fundoplication gives the best and longest
      lasting results in suitably selected patients. The extension of the myotomy and
      reduction in LES pressure are the most important parameters to achieve a good
      result.

PMID- 24091179
TI  - Sigmoid volvulus: is it a possible complication after stapled transanal rectal
      resection (STARR)?
AB  - We report a case of sigmoid volvulus post-stapled transanal rectal resection
      (STARR) for obstructed defecation. The patient, a 68-yearold woman with chronic
      constipation and dolichosigma, two days post-STARR presented severe abdominal
      pain. CT revealed sigmoid ischemia. The patient underwent resection of the
      sigmoid colon with end colostomy (Hartmann's procedure). Can STARR procedure
      produce a serious complication as sigmoid volvulus in patient with dolichosigma
      and obstructed defecation syndrome? 

PMID- 24091180
TI  - Totally laparoscopic resection of a very large gastric GIST.
AB  - Laparoscopic approach was safely performed for the diagnosis and treatment of the
      submucosal tumors of the stomach because it is associated with low morbidity,
      mortality, and sound oncologic outcomes. However, no report on the long-term
      safety and efficacy of this surgery for large sized gastric GISTs has been
      published to date. We present a 63-year-old female case of a large gastric GIST
      of 19 cm removed by laparoscopic wedge resection. 

PMID- 24091181
TI  - Risk management in surgery.
AB  - Malpractice is the responsible for the greatest number of legal claims. At the
      present time, legal actions against physicians in Italy are 15,000 per year, and
      a stunning increase about costs to refund patients injured by therapeutic and
      diagnostic errors is expected. The method for the medical prevention is "Risk
      Management", that is the setting-up of organizational instruments, methods and
      actions that enable the measurement or estimation of medical risk; it allows to
      develop strategies to govern and reduce medical error. In the present work, the
      reconstruction about the history of risk management in Italy was carried out.
      After then the latest initiatives undertaken by Italy about the issue of risk
      management were examined. 

PMID- 24091182
TI  - Mode-locking neurodynamics predict human auditory brainstem responses to musical
      intervals.
AB  - The auditory nervous system is highly nonlinear. Some nonlinear responses arise
      through active processes in the cochlea, while others may arise in neural
      populations of the cochlear nucleus, inferior colliculus and higher auditory
      areas. In humans, auditory brainstem recordings reveal nonlinear population
      responses to combinations of pure tones, and to musical intervals composed of
      complex tones. Yet the biophysical origin of central auditory nonlinearities,
      their signal processing properties, and their relationship to auditory perception
      remain largely unknown. Both stimulus components and nonlinear resonances are
      well represented in auditory brainstem nuclei due to neural phase-locking.
      Recently mode-locking, a generalization of phase-locking that implies an
      intrinsically nonlinear processing of sound, has been observed in mammalian
      auditory brainstem nuclei. Here we show that a canonical model of mode-locked
      neural oscillation predicts the complex nonlinear population responses to musical
      intervals that have been observed in the human brainstem. The model makes
      predictions about auditory signal processing and perception that are different
      from traditional delay-based models, and may provide insight into the nature of
      auditory population responses. We anticipate that the application of dynamical
      systems analysis will provide the starting point for generic models of auditory
      population dynamics, and lead to a deeper understanding of nonlinear auditory
      signal processing possibly arising in excitatory-inhibitory networks of the
      central auditory nervous system. This approach has the potential to link neural
      dynamics with the perception of pitch, music, and speech, and lead to dynamical
      models of auditory system development.

PMID- 24091183
TI  - Diagnostic performance of high-sensitive troponin T in patients with renal
      insufficiency.
AB  - In the present study, we wanted to (1) evaluate whether high-sensitive troponin T
      levels correlate with the grade of renal insufficiency and (2) test the accuracy
      of high-sensitive troponin T determination in patients with renal insufficiency
      for diagnosis of acute myocardial infarction (AMI). In this cross-sectional
      analysis, all patients who received serial measurements of high-sensitive
      troponin T from August 1, 2010, to October 31, 2012, at the Department of
      Emergency Medicine were included. We analyzed data on baseline characteristics,
      reason for referral, medication, cardiovascular risk factors, and outcome in
      terms of presence of AMI along with laboratory data (high-sensitive troponin T,
      creatinine). A total of 1,514 patients (67% male, aged 65 +/- 16 years) were
      included, of which 382 patients (25%) had moderate to severe renal insufficiency
      and significantly higher levels of high-sensitive troponin T on admission (0.028
      vs 0.009, p <0.0001). In patients without AMI, high-sensitive troponin T
      correlated inversely with the estimated glomerular filtration rate (R = -0.12, p
      <0.0001). Overall, sensitivity of an elevated high-sensitive troponin for
      diagnosis of AMI was 0.64 (0.56 to 0.71) and the specificity was 0.48 (0.45 to
      0.51). The area under the curve of the receiver operating characteristic for all
      patients was 0.613 (standard error [SE] 0.023), whereas it was 0.741 (SE 0.029)
      for patients with a Modification of Diet in Renal Disease estimated glomerular
      filtration rate >60 ml/min presenting with acute chest pain or dyspnea and 0.535
      (SE 0.056) for patients with moderate to severe renal insufficiency presenting
      with acute chest pain or dyspnea. In conclusion, the diagnostic accuracy for
      presence of AMI of a baseline measurement of high-sensitive troponin in patients
      with renal insufficiency was poor and resembles tossing a coin. 

PMID- 24091184
TI  - EU-wide monitoring survey on emerging polar organic contaminants in wastewater
      treatment plant effluents.
AB  - In the year 2010, effluents from 90 European wastewater treatment plants (WWTPs)
      were analyzed for 156 polar organic chemical contaminants. The analyses were
      complemented by effect-based monitoring approaches aiming at estrogenicity and
      dioxin-like toxicity analyzed by in vitro reporter gene bioassays, and yeast and
      diatom culture acute toxicity optical bioassays. Analyses of organic substances
      were performed by solid-phase extraction (SPE) or liquid-liquid extraction (LLE)
      followed by liquid chromatography tandem mass spectrometry (LC-MS-MS) or gas
      chromatography high-resolution mass spectrometry (GC-HRMS). Target
      microcontaminants were pharmaceuticals and personal care products (PPCPs),
      veterinary (antibiotic) drugs, perfluoroalkyl substances (PFASs), organophosphate
      ester flame retardants, pesticides (and some metabolites), industrial chemicals
      such as benzotriazoles (corrosion inhibitors), iodinated x-ray contrast agents,
      and gadolinium magnetic resonance imaging agents; in addition biological
      endpoints were measured. The obtained results show the presence of 125 substances
      (80% of the target compounds) in European wastewater effluents, in concentrations
      ranging from low nanograms to milligrams per liter. These results allow for an
      estimation to be made of a European median level for the chemicals investigated
      in WWTP effluents. The most relevant compounds in the effluent waters with the
      highest median concentration levels were the artificial sweeteners acesulfame and
      sucralose, benzotriazoles (corrosion inhibitors), several organophosphate ester
      flame retardants and plasticizers (e.g. tris(2-chloroisopropyl)phosphate; TCPP),
      pharmaceutical compounds such as carbamazepine, tramadol, telmisartan,
      venlafaxine, irbesartan, fluconazole, oxazepam, fexofenadine, diclofenac,
      citalopram, codeine, bisoprolol, eprosartan, the antibiotics trimethoprim,
      ciprofloxacine, sulfamethoxazole, and clindamycine, the insect repellent N,N'
      diethyltoluamide (DEET), the pesticides MCPA and mecoprop, perfluoroalkyl
      substances (such as PFOS and PFOA), caffeine, and gadolinium.

PMID- 24091185
TI  - Pre-exposure to nitrite in the absence of ammonium strongly inhibits anammox.
AB  - Anaerobic ammonium oxidizing bacteria (Anammox) are known to be inhibited by
      their substrate, nitrite. However, the mechanism of inhibition and the
      physiological conditions under which nitrite impacts the performance of anammox
      bioreactors are still unknown. This study investigates the role of pre-exposing
      anammox bacteria to nitrite alone on their subsequent activity and metabolism
      after ammonium has been added. Batch experiments were carried out with anammox
      granular biofilm pre-exposed to nitrite over a range of concentrations and
      durations in the absence of ammonium. The effect of pre-exposure to nitrite alone
      compared to nitrite simultaneously fed with ammonium was evaluated by measuring
      the anammox activity and the accumulation of the intermediate, nitric oxide. The
      results show that the inhibitory effect was more dramatic when bacteria were pre
      exposed to nitrite in absence of ammonium, as revealed by the lower activity and
      the higher accumulation of nitric oxide. The nitrite concentration causing 50%
      inhibition was 53 and 384 mg N L(-1) in the absence or the presence of ammonium,
      respectively. The nitrite inhibition was thus 7.2-fold more severe in the absence
      of ammonium. Biomass exposure to nitrite (25 mg N L(-1)), in absence of ammonium,
      led to accumulation of nitric oxide. On the other hand when the biomass was
      exposed to nitrite in presence of ammonium, accumulation of nitric oxide was only
      observed at much higher nitrite concentrations (500 mg N L(-1)). The inhibitory
      effect of nitrite in the absence of ammonium was very rapid. The rate of decay of
      the anammox activity was equivalent to the diffusion rate of nitrite up to 46% of
      activity loss. The results taken as a whole suggest that nitrite inhibition is
      more acute when anammox cells are not actively metabolizing. Accumulation of
      nitric oxide in the headspace most likely indicates disruption of the anammox
      biochemistry by nitrite inhibition, caused by an interruption of the hydrazine
      synthesis step.

PMID- 24091186
TI  - A novel bench-scale column assay to investigate site-specific nitrification
      biokinetics in biological rapid sand filters.
AB  - A bench-scale assay was developed to obtain site-specific nitrification
      biokinetic information from biological rapid sand filters employed in groundwater
      treatment. The experimental set-up uses granular material subsampled from a full
      scale filter, packed in a column, and operated with controlled and continuous
      hydraulic and ammonium loading. Flowrates and flow recirculation around the
      column are chosen to mimic full-scale hydrodynamic conditions, and minimize axial
      gradients. A reference ammonium loading rate is calculated based on the average
      loading experienced in the active zone of the full-scale filter. Effluent
      concentrations of ammonium are analyzed when the bench-scale column is subject to
      reference loading, from which removal rates are calculated. Subsequently, removal
      rates above the reference loading are measured by imposing short-term loading
      variations. A critical loading rate corresponding to the maximum removal rate can
      be inferred. The assay was successfully applied to characterize biokinetic
      behavior from a test rapid sand filter; removal rates at reference loading
      matched those observed from full-scale observations, while a maximum removal
      capacity of 6.9 g NH4(+)-N/m(3) packed sand/h could easily be determined at 7.5 g
      NH4(+)-N/m(3) packed sand/h. This assay, with conditions reflecting full-scale
      observations, and where the biological activity is subject to minimal physical
      disturbance, provides a simple and fast, yet powerful tool to gain insight in
      nitrification kinetics in rapid sand filters.

PMID- 24091187
TI  - Co-resistance to different classes of antibiotics among ESBL-producers from
      aquatic systems.
AB  - In this study we investigated the co-occurrence of resistance to non-beta-lactams
      among cefotaxime-resistant extended-spectrum beta-lactamase (ESBL) producers
      (ESBL(+)) versus non-ESBL producers (ESBL(-)), from aquatic environments. Higher
      prevalence of resistance to tetracycline, fluoroquinolones and aminoglycosides
      were observed in ESBL(+). Among ESBL(+) resistant to tetracycline (n = 18),
      tet(A) was detected in 88.9% and tet(B) in 16.7%. Among fluoroquinolone-resistant
      ESBL(+) (n = 15), aacA4-cr and qnrVC4 were identified in 26.6% and 40% strains,
      respectively. The qnrVC4 gene was detected for the first time in Pseudomonas sp.
      and Escherichia coli. Class 1 integrase genes were detected in 56.41% of ESBL(+)
      and in 27.67% ESBL(-). Gene cassette arrays identified conferred resistance to
      aminoglycosides (aadA-type genes and aacA4), trimethoprim (dfrA17),
      chloramphenicol (catB8), fluoroquinolones (qnrVC4) and beta-lactams (blaOXA-10).
      Conjugation experiments were performed with CTX-M-producers. Transconjugants
      showed multiresistance to 3 or more classes of antibiotics, and conjugative
      plasmids were assigned to IncF, IncK and IncI1 replicons. Results obtained showed
      that co-selection of resistance to aminoglycosides, quinolones and tetracyclines
      is prevalent among ESBL-producers and that these features are successfully
      mobilized by IncF, IncK and IncI1 conjugative plasmids. This study reinforces the
      importance of natural aquatic systems as reservoir of mobile genetic platforms
      carrying multiple resistance determinants. Moreover, to the best of our
      knowledge, this constitutes the first observation of IncK::CTX-M-3 in Aeromonas
      hydrophila and the first report of IncK plasmids in Portugal.

PMID- 24091188
TI  - Sediment-water interactions of pharmaceutical residues in the river environment.
AB  - To assess the environmental fate and risks of pharmaceuticals, the determination
      of their distributions between sediment and water is crucial as a controlling
      process. In this paper, the concentrations of 9 selected pharmaceuticals were
      determined in water and sediment samples from the River Medway, Kent, UK between
      December 2009 and December 2010. In the water phase, there was a spatial
      variation of concentration with the highest concentrations being detected in the
      sewage outfall, indicating it being an important point source in the river. In
      terms of seasonal variations, the highest concentrations (13-878 ng L(-1)) were
      detected in June 2010. In the surface sediment phase, the highest concentrations
      (5.3-33.6 ng g(-1) dry weight) were observed at the sewage outfall, although in
      February 2010 the highest concentrations were detected downstream of the sewage
      outfall indicating a delayed response in sediment accumulation of pharmaceuticals
      in relation to the water phase. The partition coefficient of pharmaceuticals
      between surface sediment and water was variable, reflecting a dynamic process of
      sediment-water interaction and the varying nature of sediments. Overall the
      partition coefficient was shown to decrease with an increase in suspended
      sediment concentration. The organic carbon normalized partition coefficient of
      the pharmaceuticals was shown to be positively related to their molecular weight
      (MW), suggesting that sediment-water interactions were partly a partition process
      favoring large molecules.

PMID- 24091189
TI  - Survival of Escherichia coli in two sewage treatment plants using UV irradiation
      and chlorination for disinfection.
AB  - We investigated the survival of Escherichia coli in two STPs utilising UV
      irradiation (STP-A) or chlorination (STP-B) for disinfection. In all, 370 E. coli
      strains isolated from raw influent sewage (IS), secondary treated effluent (STE)
      and effluent after the disinfection processes of both STPs were typed using a
      high resolution biochemical fingerprinting method and were grouped into common (C
      ) and single (S-) biochemical phenotypes (BPTs). In STP-A, 83 BPTs comprising 123
      isolates were found in IS and STE, of which 7 BPTs survived UV irradiation.
      Isolates tested from the same sites of STP-B (n = 220) comprised 122 BPTs,
      however, only two BPTs were found post-chlorination. A representative isolate
      from each BPT from both STPs was tested for the presence of 11 virulence genes
      (VGs) associated with uropathogenic (UPEC) or intestinal pathogenic (IPEC) E.
      coli strains. Strains surviving UV irradiation were distributed among seven
      phylogenetic groups with five BPTs carrying VGs associated with either UPEC (4
      BPTs) or IPEC (1 BPT). In contrast, E. coli strains found in STP-B carried no
      VGs. Strains from both STPs were resistant to up to 12 out of the 21 antibiotics
      tested but there was no significant difference between the numbers of antibiotics
      to which surviving strains were resistant to in these STPs. Our data suggests
      that some E. coli strains have a better ability to survive STPs utilising
      chlorination and UV irradiation for disinfection. However, strains that survive
      UV irradiation are more diverse and may carry more VGs than those surviving SPTs
      using chlorination.

PMID- 24091190
TI  - Polybrominated diphenyl ethers in sewage sludge and treated biosolids: effect
      factors and mass balance.
AB  - Polybrominated diphenyl ether (PBDE) flame retardants have been consistently
      detected in sewage sludge and treated biosolids. Two hundred and eighty-eight
      samples including primary sludge (PS), waste biological sludge (WBS) and treated
      biosolids from fifteen wastewater treatment plants (WWTPs) in Canada were
      analyzed to investigate the factors affecting accumulation of PBDEs in sludge and
      biosolids. Factors examined included environmental/sewershed conditions and
      operational parameters of the WWTPs. PBDE concentrations in PS, WBS and treated
      biosolids were 230-82,000 ng/g, 530-8800 ng/g and 420-6000 ng/g, respectively;
      BDE-209,-99, and -47 were the predominant congeners. Concentrations were
      influenced by industrial input, leachate, and temperature. Several examinations
      including the measurement of BDE-202 indicated minimal debromination during
      wastewater treatment. Estimated solids-liquid distribution coefficients were
      moderately correlated to hydraulic retention time, solids loading rate, mixed
      liquor suspended solids, solids retention time, and removal of organic solids,
      indicating that PBDE partitioning to solids can be optimized by WWTPs'
      operational conditions. Solids treatment type strongly affected PBDE levels in
      biosolids: 1.5 times increase after solids digestion, therefore, digestion
      efficiency could be a potential factor for variability of PBDEs concentration. In
      contrast, alkaline treatment reduced PBDE concentrations in biosolids. Overall,
      mass balance approaches confirmed that PBDEs were removed from the liquid stream
      through partitioning to solids. Variability of PBDE levels in biosolids could
      result in different PBDEs burdens to agricultural land, and different exposure
      levels to soil organisms.

PMID- 24091191
TI  - Experimental and computational investigations of the interactions between model
      organic compounds and subsequent membrane fouling.
AB  - The formation of aggregates of sodium alginate and bovine serum albumin (BSA) (as
      representative biopolymers) with humic acid were detected by Liquid
      Chromatography (LC) UV254 response in the biopolymer region for mixture
      solutions. BSA interaction with humic acid showed that aggregation occurred both
      in the presence and absence of calcium, suggesting that multivalent ions did not
      play a part in the aggregation process. Similar analyses of the alginate
      interaction with humic acid also showed a positive interaction, but only in the
      presence of calcium ions. The fouling characteristics for the BSA-humic acid
      mixture appeared to be significantly greater than the fouling characteristics of
      the individual solutions, while for the sodium alginate-humic acid mixture, the
      fouling rate was similar to that of the sodium alginate alone. The effectiveness
      of hydraulic backwashing, 10-15% reversibility, was observed for the BSA-humic
      acid mixture, while the % reversibility was 20-40% for the sodium alginate-humic
      acid mixture. Increased humic acid and DOC rejection were observed for both BSA
      humic acid and sodium alginate-humic acid solutions compared to the individual
      solutions, indicating that the biopolymer filter cakes were able to retain humic
      acids. When compared with BSA-humic acid mixture solution, greater removal of
      humic acid was observed for alginate-humic mixture, suggesting that sodium
      alginate may have a greater capacity for associations with humic acid when in the
      presence of calcium than BSA. Complementary molecular dynamics simulations were
      designed to provide insights into the specific mechanisms of interaction between
      BSA and humic acid, as well as between alginate and humic acid. For the BSA-humic
      acid system; electrostatic, hydrophobic and hydrogen bonding were the dominant
      types of interactions predicted, whilst divalent ion-mediated bonding was not
      identified in the simulations, which supported the LC-results. Similarly for the
      alginate-humic acid system, the interactions predicted were divalent ion-mediated
      interactions only and this was also supported the LC results. This work suggests
      that LC-UV254 might be used to identify aggregated biopolymers, and that combined
      with current characterisation techniques, be used to better explain performance
      variations between water sources. 

PMID- 24091192
TI  - Hot topics in infection and immunity in children--Papers from the 10th annual IIC
      meeting, Oxford, UK, 2012. Preface.

PMID- 24091193
TI  - Modified active disturbance rejection control for time-delay systems.
AB  - Industrial processes are typically nonlinear, time-varying and uncertain, to
      which active disturbance rejection control (ADRC) has been shown to be an
      effective solution. The control design becomes even more challenging in the
      presence of time delay. In this paper, a novel modification of ADRC is proposed
      so that good disturbance rejection is achieved while maintaining system
      stability. The proposed design is shown to be more effective than the standard
      ADRC design for time-delay systems and is also a unified solution for stable,
      critical stable and unstable systems with time delay. Simulation and test results
      show the effectiveness and practicality of the proposed design. Linear matrix
      inequality (LMI) based stability analysis is provided as well. 

PMID- 24091194
TI  - Study on a linear relationship between limited pressure difference and coil
      current of on/off valve and its influential factors.
AB  - On/off solenoid valves with PWM control are widely used in all types of vehicle
      electro-hydraulic control systems respecting to their desirable properties of
      reliable, low cost and fast acting. However, it can hardly achieve a linear
      hydraulic modulation by using on/off valves mainly due to the nonlinear behaviors
      of valve dynamics and fluid, which affects the control accuracy significantly. In
      this paper, a linear relationship between limited pressure difference and coil
      current of an on/off valve in its critical closed state is proposed and
      illustrated, which has a great potential to be applied to improve hydraulic
      control performance. The hydraulic braking system of case study is modeled. The
      linear correspondence between limited pressure difference and coil current of the
      inlet valve is simulated and further verified experimentally. Based on validated
      simulation models, the impacts of key parameters are researched. The limited
      pressure difference affected by environmental temperatures is experimentally
      studied, and the amended linear relation is given according to the test data. 

PMID- 24091195
TI  - Enteroendocrine hormones - central effects on behavior.
AB  - A number of appetite-regulating gut hormones alter behaviors linked to reward,
      anxiety/mood, memory and cognitive function, although for some of these (notably
      GLP-1 and CCK) the endogenous signal may be CNS-derived. From a physiological
      perspective it seems likely that these hormones, whose secretion is altered by
      nutritional status and by bariatric weight loss surgery, orchestrate
      neurobiological effects that are integrated and linked to feeding/metabolic
      control. Consistent with a role in hunger and meal initiation, ghrelin increases
      motivated behavior for food and, when food is not readily available, decreases
      behaviors in anxiety tests that would otherwise hinder the animal from finding
      food. Of the many anorexigenic signals, GLP-1 and PYY have been linked to a
      suppressed reward function and CCK (and possibly GLP-1) to increased anxiety-like
      behavior. 

PMID- 24091197
TI  - Regarding "Repeated pulse intramuscular injection of pralidoxime chloride in
      severe acute organophosphorus pesticide poisoning".

PMID- 24091196
TI  - Comparative analysis of mitochondrial markers from four species of Rhipicephalus
      (Acari: Ixodidae).
AB  - Mitochondrial sequences of four mitochondrial markers: 12S rRNA, 16S rRNA,
      cytochrome c oxidase subunit I (COX1) and cytochrome b (CytB) from four
      Rhipicephalus species were analyzed to establish genetic relationships and enable
      molecular identification. Field-collected samples from the species Rhipicephalus
      annulatus, Rhipicephalus bursa, Rhipicephalus sanguineus and Rhipicephalus
      turanicus were amplified by PCR and compared with GenBankTM annotated sequences.
      PCR products were obtained using primers that were designed to amplify
      orthologous sequences from different tick species and genera. The average intra
      species sequence identity was 98.5-99.5%, while the average inter-species
      identity was 86.5-89.6%, reflecting a ~ 10% decrease in the identity, when
      different species are compared. The "closest" two species, in terms of sequence
      identity, were R. sanguineus and R. turanicus, while the "least close" ones were
      R. annulatus and R. sanguineus. Molecular identification of each species was
      accomplished by a combined restriction analysis of 12S, COX1 and CytB markers,
      obviating the need for field sample sequencing. The restriction mapping data
      suggest that by using several markers, each with a unique digestion pattern, the
      identity of a given sample could be determined at the species level. It is
      anticipated that with the accumulation of more information on additional species
      and markers, molecular identification will become a standard approach for tick
      classification, complementing morphological taxonomy.

PMID- 24091198
TI  - Postresuscitation myocardial dysfunction after asphyxial cardiac arrest: is it
      time to reconsider the existing paradigm?

PMID- 24091199
TI  - Compartment syndrome as a complication of ileofemoral deep venous thrombosis:a
      case presentation.
AB  - A 22-year-old morbidly obese, nonpregnant woman presented with left ileofemoral
      deep vein thrombosis (DVT) presenting as low back pain and bilateral, left
      greater than right, leg swelling and pain for 2 days. While on heparin, she
      developed compartment syndrome in her left leg and had evidence of dead muscle
      tissue at the time of fasciotomy. Three options exist for treatment of
      ileofemoral DVT: catheter-directed thrombolysis (CDT), CDT plus
      pharmacomechanical thrombolysis or percutaneous mechanical thrombectomy, and
      surgical thrombectomy. Catheter-directed thrombolysis alone or in conjunction
      with pharmacomechanical thrombolysis in patients with low risk of bleeding has
      shown significant lysis of occlusion in 79% of patients with ileofemoral DVT with
      relatively low complication rates. Surgical thrombectomy and fasciotomy have not
      proven to be as effective but are appropriate alternatives if CDT is not
      available. Standard anticoagulation alone is likely not a sufficient treatment
      for ileofemoral DVT. Other therapies including CDT, CDT plus pharmacomechanical
      thrombolysis or percutaneous mechanical thrombectomy, or surgical thrombectomy to
      address lysis of the clot should be attempted first or in conjunction with
      anticoagulation for appropriate patients. Catheter-directed thrombolysis with or
      without pharmacomechanical thrombolysis is the preferred initial treatment.

PMID- 24091200
TI  - Anaphylactic shock associated with intravenous thrombolytics.
AB  - Adverse events including intracerebral hemorrhage and reperfusion arrhythmias are
      well known to occur with thrombolytic therapy. We report a case report of
      anaphylactic reaction directly attributable to intravenous (IV) recombinant
      tissue plasminogen activator and identify additional cases through review of the
      Food and Drug Administration Adverse Event Reporting System. A systematic review
      of Adverse Event Reporting System was performed for allergic adverse events
      occurring in conjunction with IV thrombolytics. We reviewed 924 adverse events
      which occurred between 2004 and 2012 that were associated with thrombolytics. We
      subsequently acquired detailed individual safety reports of 33 cases in which
      allergic events were documented. Out of the 33 reports, there were 12 cases (age
      range, 57-93 years) of adverse allergic reaction directly attributable to IV
      thrombolytics. Allergic reactions included angioedema, facial swelling,
      urticaria, skin rash, cutaneous hypesthesia, hypotension, anaphylactic shock, and
      death. Of the patients who were reported to suffer from allergic adverse events,
      11 received IV alteplase and 1 received IV reteplase. Most reactions associated
      with IV alteplase resolved with withdrawal of medication and treatment with
      diphenhydramine and steroids +/- epinephrine. There was 1 death directly
      attributable to allergic reaction in a patient who received IV reteplase for
      MI.Although IV alteplase is identical to endogenous tissue plasminogen activator,
      it appears to be the most common cause of allergic reaction among currently used
      thrombolytics, with or without concomitant administration of angiotensin
      converting enzyme inhibitors. A greater awareness among physicians may result in
      prompt recognition and treatment.

PMID- 24091201
TI  - A new marker for myocardial injury in carbon monoxide poisoning: T peak-T end.
AB  - OBJECTIVES: Carbon monoxide (CO) poisoning frequently affects repolarization,
      resulting in abnormal electrocardiography findings. The goal of this study was to
      examine the effect of CO poisoning on the novel transmyocardial repolarization
      parameters T peak-T end (Tp-e), Tp-e dispersion, and Tp-e/QT and the relationship
      of these parameters to myocardial injury (MI). METHODS: This prospective study
      included 94 patients with CO poisoning and 40 healthy controls. Participants
      received an electrocardiography and had their blood drawn at admission and 6 and
      24 hours after admission. The QT, Tp-e, Tp-e dispersion, and the Tp-e/QT ratio
      were calculated. Myocardial injury was determined based on an elevation in
      troponin any time during the first 24 hours. The patients were divided into 2
      subgroups: those with and without MI. RESULTS: T peak-T end, Tp-e dispersion, and
      the Tp-e/QT ratio were higher at admission than after 6 and 24 hours of
      hospitalization and were higher than the control group (P < .001). There was a
      correlation between the carboxyhemoglobin level at admission and Tp-e and Tp-e
      dispersion (P < .001). The MI subgroup (n = 14) had a higher Tp-e at admission
      than did the non-MI subgroup (n = 80) (96 [11] milliseconds vs 87 [12]
      milliseconds, P = .03). There were no any significant differences in the Tp-e
      dispersion or the Tp-e/QT ratio between the 2 MI subgroups. Receiver operating
      characteristic analysis showed that a Tp-e cutoff value for MI of 91.5
      milliseconds had a sensitivity of 72.7% and a specificity of 67.2%. CONCLUSION:
      Transmyocardial repolarization parameters indicative of arrhythmia were prolonged
      in patients with CO poisoning. T peak-T end was associated with MI.

PMID- 24091202
TI  - Does change in distress matter? Mechanisms of change in prolonged exposure for
      PTSD.
AB  - BACKGROUND AND OBJECTIVES: Clinically, many individuals persist in prolonged
      exposure therapy (PE) for chronic PTSD despite continuing distress during
      recounting of the trauma memory (imaginal exposure). Theorists suggest that
      distress reduction is necessary for successful treatment outcome (e.g., Foa &
      Kozak, 1986), while others suggest otherwise (e.g., Craske et al., 2008). This
      study examined clinically reliable changes in distress, relations to broad
      clinical outcomes, and whether homework adherence affected this relationship.
      METHOD: In 116 patients with PTSD, first to last imaginal exposure sessions' peak
      and average distress was examined, calculating reliable change in distress.
      Homework adherence and helpfulness were examined. At post-treatment, PTSD
      symptoms (re-experiencing, avoidance, hyperarousal), depression, and functioning
      were examined. RESULTS: Patients exhibited a lack of reliable change in distress
      (64.7%) more than a reliable change in distress (35.3%). Although no difference
      in post-treatment PTSD diagnostic status, individuals experiencing a reliable
      change in distress reported lower PTSD severity (re-experiencing, hyperarousal),
      depression, and better functioning. Further, perceived helpfulness of imaginal
      homework had an indirect effect on this relationship. LIMITATIONS: This study did
      not utilize a distress tolerance self-report measure; however, examined self
      reported distress during imaginal exposure. CONCLUSIONS: Results are encouraging
      for clinicians treating PTSD with PE, arguing that lack of reliable change in
      distress to the trauma memory does not result in treatment failure. Patient "buy
      in" to homework, rather than amount completed, was related to the process of
      distress reduction. Results suggest that distress reduction in imaginal exposure
      is not a key mechanism underlying therapeutic change in PE.

PMID- 24091203
TI  - Host-targeting agents in the treatment of hepatitis C: a beginning and an end?
AB  - The development of two distinct classes of hepatitis C antiviral agents, direct
      acting antivirals (DAAs) and host-targeting antivirals (HTAs), have distinctly
      impacted the hepatitis C virus (HCV) field by generating higher sustained
      virological response (SVR) rates within infected patients, via reductions in both
      adverse side effects and duration of treatment when compared to the old standard
      of care. Today DAAs are actively incorporated into the standard of care and
      continue to receive the most advanced clinical trial analysis. With a multitude
      of innovative and potent second-generation DAA compounds currently being tested
      in clinical trials, it is clear that the future of DAAs looks very bright. In
      comparison to the other class of compounds, HTAs have been slightly less
      impactful, despite the fact that primary treatment regimens for HCV began with
      the use of an HTA - interferon alpha (IFNalpha). The compound was advantageous in
      that it provided a broad-reaching antiviral response; however deleterious side
      effects and viral/patient resistance has since made the compound outdated. HTA
      research has since moved onward to target a number of cellular host factors that
      are required for HCV viral entry and replication such as scavenger receptor-BI
      (SR-BI), 3-hydroxy-3-methyl-glutaryl-CoA reductase (HMGCoA reductase),
      cyclophilin A (CypA), fatty acid synthase (FASN) and miRNA-122. The rationale
      behind pursuing these HTAs is based upon the extremely low mutational rate that
      occurs within eukaryotic cells, thereby creating a high genetic barrier to drug
      resistance for anti-HCV compounds, as well as pan-genotypic coverage to all HCV
      genotypes and serotypes. As the end appears near for HCV, it becomes important to
      ask if the development of novel HTAs should also be analyzed in combination with
      other DAAs, in order to address potential hard-to-treat HCV patient populations.
      Since the treatment regimens for HCV began with the use of a global HTA, could
      one end the field as well? 

PMID- 24091204
TI  - Universal anti-neuraminidase antibody inhibiting all influenza A subtypes.
AB  - The only universally conserved sequence amongst all influenza A viral
      neuraminidase (NA) is located between amino acids 222-230 and plays crucial roles
      in viral replication. However, it remained unclear as to whether this universal
      epitope is exposed during the course of infection to allow binding and inhibition
      by antibodies. Using a monoclonal antibody (MAb) targeting this specific epitope,
      we demonstrated that all nine subtypes of NA were inhibited in vitro by the MAb.
      Moreover, the antibody also provided heterosubtypic protection in mice challenged
      with lethal doses of mouse-adapted H1N1 and H3N2, which represent group I and II
      viruses, respectively. Furthermore, we report amino acid residues I222 and E227,
      located in close proximity to the active site, are indispensable for inhibition
      by this antibody. This unique, highly-conserved linear sequence in viral NA could
      be an attractive immunological target for protection against diverse strains of
      influenza viruses. 

PMID- 24091205
TI  - Persistence of amygdala gamma oscillations during extinction learning predicts
      spontaneous fear recovery.
AB  - Extinction of auditory fear conditioning induces a temporary inhibition of
      conditioned fear responses that can spontaneously reappear with the passage of
      time. Several lines of evidence indicate that extinction learning relies on the
      recruitment of specific neuronal populations within the basolateral amygdala. In
      contrast, post-extinction spontaneous fear recovery is thought to result from
      deficits in the consolidation of extinction memory within prefrontal neuronal
      circuits. Interestingly, recent data indicates that the strength of gamma
      oscillations in the basolateral amygdala during auditory fear conditioning
      correlates with retrieval of conditioned fear responses. In the present
      manuscript we evaluated the hypothesis that post-extinction spontaneous fear
      recovery might depend on the maintenance of gamma oscillations within the
      basolateral amygdala by using single unit and local field potential recordings in
      behaving mice. Our results indicate that gamma oscillations in the basolateral
      amygdala were enhanced following fear conditioning, whereas during extinction
      learning gamma profiles were more heterogeneous despite similar extinction
      learning rates. Remarkably, variations in the strength of gamma power within the
      basolateral amygdala between early and late stages of extinction linearly
      predicted the level of post-extinction spontaneous fear recovery. These data
      suggest that maintenance of gamma oscillations in the basolateral amygdala during
      extinction learning is a strong predictive factor of long term spontaneous fear
      recovery. 

PMID- 24091206
TI  - Pathogen regulation of plant diversity via effective specialization.
AB  - The Janzen-Connell (JC) hypothesis, one of the most influential hypotheses
      explaining forest diversity, is inconsistent with evidence that tree species
      share the same natural enemies. Through the discussion of seedling diseases from
      a pathogen-centered perspective, we expand the JC hypothesis to tie in host
      pathogen-environment interactions at three levels: local adaptation, host
      specificity of the combined effect of multiple infections, and environmental
      modulation of disease. We present evidence from plant pathology, disease ecology,
      and host-parasite evolution relevant to (but not commonly associated with) forest
      species diversity maintenance. This expanded view of the JC hypothesis suggests
      ways to direct new experiments to integrate research on pathogen local
      adaptation, co-infection, and environmental effects on infection by using high
      throughput molecular techniques and statistical models. 

PMID- 24091207
TI  - Cryptic or mystic? Glacial tree refugia in northern Europe.
AB  - Here, we examine the evidence for tree refugia in northern Europe during the Late
      Pleniglacial (LPG) interval of maximum tree-range contraction. Our review
      highlights the often equivocal nature of genetic data and a tendency to
      overestimate potential tree distributions due to warm climate-model bias, and
      also reveals a convergence of macrofossil and pollen evidence. What emerges is
      the absence of temperate trees north of 45 degrees N and a west-east (W-E)
      asymmetry in boreal tree distribution, with a treeless Western Europe north of 46
      degrees N, while restricted boreal populations persisted in Eastern Europe up to
      49 degrees N, and higher latitudes east of the Fennoscandian ice-sheet. These
      results have implications for current thinking on European genetic diversity
      patterns, species migration capacity, and conservation strategies. 

PMID- 24091208
TI  - Darwinian shortfalls in biodiversity conservation.
AB  - If we were to describe all the species on Earth and determine their
      distributions, we would solve the popularly termed 'Linnean' and 'Wallacean'
      shortfalls in biodiversity conservation. Even so, we would still be hindered by a
      'Darwinian shortfall', that is, the lack of relevant phylogenetic information for
      most organisms. Overall, there are too few comprehensive phylogenies, large
      uncertainties in the estimation of divergence times, and, most critically,
      unknown evolutionary models linking phylogenies to relevant ecological traits and
      life history variation. Here, we discuss these issues and offer suggestions for
      further research to support evolutionary-based conservation planning. 

PMID- 24091209
TI  - A visit to Absurdistan: a nightmare of a sleep specialist.
AB  - During a nocturnal dream, the authors discover a strange and unknown country,
      Absurdistan. Absurdistanis main concern appears to be sleep, whether nocturnal or
      diurnal, rather than wakefulness. They are fond of sleeping in any form, and
      devote much time to this activity. The authors follow a guide that shows them all
      kinds of strange sleep habits and keeps explaining the complex as well as the
      obvious. As the journey evolves, the explanations turn more and more confusing,
      becoming also amazingly surrealistic. The dream ends with a welcome wakefulness
      leaving the authors unsure of which is the waking state and which the dream. 

PMID- 24091210
TI  - Working to the breadth of our licence.

PMID- 24091212
TI  - President's message. Generalism is dead: Long live generalism!

PMID- 24091214
TI  - The outcomes of perinatal surgical services in rural British Columbia: a
      population-based study.
AB  - INTRODUCTION: A substantial number of small surgical services in rural Canada
      have been discontinued in the past 15 years because of difficulties recruiting
      and retaining practitioners, health care restructuring and a lack of a coherent
      evidence base regarding the safety of small services. The objective of this study
      was to examine the safety of small perinatal surgical services. METHODS: We
      accessed perinatal data for singleton births that occurred in British Columbia
      between Apr. 1, 2000, and Mar. 31, 2007. We defined hospital service levels,
      population catchment areas surrounding each hospital and the postal codes linked
      to those catchment areas. Births were linked with specific catchment areas and
      amalgamated by service level. We made comparisons among service strata
      populations and adjusted for potentially confounding characteristics. RESULTS: A
      total of 87 294 births occurred during the study period. The births were
      distributed across 6 strata of services, which ranged from no local maternity
      services to services supported by obstetricians. Fifteen catchment areas were
      served by general practitioners with enhanced surgical skills (GPESSs), and 9174
      births were included from this obstetric service level. Outcomes for surgical
      services provided by GPs compared favourably to those provided by obstetricians.
      CONCLUSION: Our results suggest that small surgical services supported by GPESSs
      are a safe health services model to meet the needs of rural women and families.

PMID- 24091215
TI  - Procedural sedation and analgesia in rural and regional emergency departments.
AB  - INTRODUCTION: Several agents can be administered during procedural sedation and
      analgesia (PSA) in the emergency department (ED). The purpose of this study was
      to determine the PSA agents commonly used by physicians working in nontertiary
      EDs, and to assess the physicians' comfort level administering the agents as well
      as their knowledge of adverse effects of the agents. METHODS: We distributed a
      confidential electronic survey to physicians working in nontertiary EDs in
      southwestern Ontario. Using a 5-point Likert scale, ED physicians were asked to
      rate their use of older and newer agents used for PSA in the ED, as well as their
      familiarity with the agents. RESULTS: A total of 55 physicians completed the
      survey. The most frequently used drugs were fentanyl (66.0% often or always) and
      propofol with fentanyl (59.2% often or always). Most respondents stated that they
      rarely used ketofol (54.2% rarely or never) or etomidate (77.1% rarely or never).
      Respondents were most comfortable using midazolam or fentanyl (96.1% somewhat or
      very comfortable), and least comfortable administering etomidate and ketofol
      (36.5% and 23.1% somewhat or very uncomfortable). These differences were
      magnified with comparison of physicians with CCFP (Certification in The College
      of Family Physicians) and CCFP(EM) (emergency medicine) designations.
      Additionally, etomidate's adverse effects were the least astutely recognized
      (19%), compared with midazolam combined with fentanyl (63%). CONCLUSION:
      Physicians practising in nontertiary EDs used more often, remained more
      comfortable with and were more familiar with older sedation agents than newer
      agents.

PMID- 24091216
TI  - The changing face of cellulitis and MRSA in rural Canada: a clinical update.

PMID- 24091217
TI  - The occasional corneal rust ring removal.

PMID- 24091220
TI  - Four pushes later, and not a word more.

PMID- 24091218
TI  - Country cardiograms case 49.

PMID- 24091223
TI  - Alcohol exacerbates LPS-induced fibrosis in subclinical acute pancreatitis.
AB  - The role of pancreatic acinar cells in initiating fibrogenic responses during the
      early stages of alcoholic acute pancreatitis has not been evaluated. We
      investigated the ability of injured acinar cells to generate pancreatic fibrosis
      in acute pancreatitis. Rats were fed either an ethanol-containing or control diet
      over 14 weeks and euthanized 3 or 24 hours after a single lipopolysaccharide
      injection. Profibrotic transforming growth factor-beta of acinar cells and
      pancreatic fibrosis were assessed by immunofluorescence, histological
      characteristics, and electron microscopy. Human pancreatic tissues were also
      evaluated. Periacinar cell fibrosis and collagen were exacerbated 24 hours after
      endotoxemia in alcohol-fed rats. Alcohol exposure exacerbated acinar cell
      specific production of transforming growth factor beta in response to
      lipopolysaccharide in vivo and in acinar cell-like AR42J cells in vitro. Although
      a morphological examination showed no visible signs of necrosis, early pancreatic
      fibrosis can be initiated by little or no pancreatic necrosis. Transforming
      growth factor beta was also significantly increased in human acinar cells from
      patients with acute/recurrent pancreatitis compared with chronic pancreatitis
      tissue. Alcohol exacerbates lipopolysaccharide-induced pancreatic fibrosis during
      the early onset of mild, subclinical, acute pancreatitis. We suggest that
      multiple, subclinical, acute pancreatitis episodes can accumulate in fibrosis
      during the development of chronic pancreatitis, even if there is no history of
      acute pancreatitis.

PMID- 24091224
TI  - President's page: an urgent call to action: graduate medical education funding
      and the future of health care.

PMID- 24091222
TI  - Phenotypic transitions of macrophages orchestrate tissue repair.
AB  - Macrophages are essential for the efficient healing of numerous tissues, and they
      contribute to impaired healing and fibrosis. Tissue repair proceeds through
      overlapping phases of inflammation, proliferation, and remodeling, and
      macrophages are present throughout this progression. Macrophages exhibit
      transitions in phenotype and function as tissue repair progresses, although the
      precise factors regulating these transitions remain poorly defined. In
      efficiently healing injuries, macrophages present during a given stage of repair
      appear to orchestrate transition into the next phase and, in turn, can promote
      debridement of the injury site, cell proliferation and angiogenesis, collagen
      deposition, and matrix remodeling. However, dysregulated macrophage function can
      contribute to failure to heal or fibrosis in several pathological situations.
      This review will address current knowledge of the origins and functions of
      macrophages during the progression of tissue repair, with emphasis on skin and
      skeletal muscle. Dysregulation of macrophages in disease states and therapies
      targeting macrophage activation to promote tissue repair are also discussed. 

PMID- 24091225
TI  - Refocusing the agenda on cardiovascular guidelines: an announcement from the
      National Heart, Lung, and Blood Institute.

PMID- 24091226
TI  - The next steps in developing clinical practice guidelines for prevention.

PMID- 24091227
TI  - Comparison of effects of human serum and horse serum on in vitro susceptibility
      testing of echinocandins.

PMID- 24091228
TI  - [And daily the marmot greets me].

PMID- 24091229
TI  - [Clinical and endocrinological findings of bitches with ovarian cyst syndrome].
AB  - Aim of this study was to record the clinical findings in bitches with ovarian
      cyst syndrome (OCS) and to interpret them in connection with the endocrine status
      in peripheral blood and in cyst liquid. For our investigation 16 bitches of
      different breeds with an average age of 9.7 years were used. They have been
      presented to the clinic due to different gynecological symptoms. The leading
      symptom was in 87.5 % of the cases a chronic vaginal secretion. In addition to a
      detailed anamnesis a clinical examination was performed including
      vaginalcytologic, sonographic, hematologic and hormonal findings (progesterone
      P4, 17beta estradiol E2). As basic diagnoses could be made: Cycle aberrations (n
      = 8), pyometra endometritis complex (n = 4), vaginal tumor (n = 4). In addition 3
      patients were presented with alopecia. All patients were ovariohysterectomized
      without prior conservative treatment and the ovaries histologically examined and
      classified. Based on sonographic findings before and macroscopic evaluation the
      ovaries after surgery, the OCS could be divided into an oligocystic and
      polycystic syndrome. There were predominating (94 %) follicle theca cysts. The
      formation of cysts on the ovary was in the vast majority (66.7 %) combined with
      corpora lutea. The endometrium showed mainly (50 %) a glandular cystic
      hyperplasia (CHE) and the hematologic examination revealed in 31.2 % of the
      patients a combination of advanced erythropenia and thrombocytopenia. Generally
      there was no direct relationship between increased P4 and E2 values in the pooled
      cyst fluid and in the peripheral blood when the oestrous phase was considered.
      Based on present data the diagnosis of OCS of the bitch by means of peripheral P4
      and E2 values is not possible. 

PMID- 24091230
TI  - Comparison of two treatment regimens with trilostane in dogs with pituitary
      dependent hyperadrenocorticism.
AB  - Trilostane is used to treat dogs with pituitary-dependent hyperadrenocorticism
      (PDH). In our institution, it was initially dosed based on bodyweight (BW)
      categories, since April 06 it is dosed per kg BW. Our objectives were to compare
      effectiveness, number of dose adjustments and side effects of the two dose
      regimens in dogs with PDH. Dogs of group 1 (28 dogs) received trilostane based on
      BW categories (< 5 kg, 30 mg; 5 - 20 kg, 60 mg and > 20 kg, 120 mg; SID); dogs of
      group 2 (20 dogs) received 2 - 5 mg/kg SID. Treatment goal was a post-ACTH
      cortisol of 1 - 2.5 and 1.5 - 5.4 ug/dl in group 1 and 2, respectively. Starting
      doses were significantly higher in group 1 and stayed higher until re-check at 4 
      7 months. Baseline and post-ACTH cortisol were significantly decreased compared
      to pre-treatment at all time points in both groups. Significantly more dogs of
      group 2 (5/20) needed a dose increase at the first re-check and significantly
      more dogs of group 1 (10/23) a dose reduction at the last re-check. Intermittent
      discontinuation was necessary in 25 and 10 % of dogs of group 1 and 2,
      respectively. We conclude that dosing per kg BW results in comparable clinical
      improvement, decrease in cortisol, but lower risk of side effects. 

PMID- 24091231
TI  - [Allopurinol therapy in imported dogs with leishmaniasis treated outside the
      endemic area].
AB  - Canine leishmaniosis (CL) has become one of the most frequently diagnosed travel
      associated infection in dogs in Switzerland and Germany. The aim of the study was
      to define recommendations for treatment with allopurinol and follow-up
      examinations of dogs with CL in a non endemic area. 31 dogs infected with
      Leishmania were treated with allopurinol (10 - 15 mg/kg twice daily, per os) and
      the effectiveness was examined. The diagnosis had been confirmed by the detection
      of specific anti-Leishmania antibodies and/or Leihmania-DNA. 22 dogs had clinical
      signs (skin lesions, lameness or lack of fitness) and 9 dogs were asymptomatic
      but showed abnormal laboratory parameters. Under treatment with allopurinol the
      symptoms disappeared within 1 - 5 months in 20 dogs. 

PMID- 24091233
TI  - [Return of bovine tuberculosis to Switzerland].

PMID- 24091232
TI  - Seizure activity occurring in two dogs after S-ketamine-induction.
AB  - Two healthy dogs were anaesthetized to undergo elective orthopaedic procedures.
      After premedication with methadone and acepromazine, general anaesthesia was
      induced with midazolam and S-ketamine. Immediately after anaesthetic induction,
      seizures occurred in both dogs. In the first dog the syndrome was characterized
      by tonic and clonic motor activity, muscular hypertone, hypersalivation,
      urination, defecation and hyperthermia. In the second dog muscular twitches of
      the temporal and masseter regions were observed, followed by increased skeletal
      muscles tone, hypersalivation, spontaneous urination and increase in body
      temperature. Recoveries from anaesthesia were uneventful and no seizures were
      observed. Considering the temporal association between anaesthetic induction and
      occurrence of seizures, and the fact that other causative factors could not be
      identified, it is hypothesized that S-ketamine played a role in determining the
      convulsive phenomena observed in these patients. S-ketamine might carry the
      potential for inducing seizures in otherwise healthy dogs, despite the
      concomitant use of GABA-ergic drugs. 

PMID- 24091234
TI  - [The disqualified investigation: recognition from a year's experience with the
      new possibility for early diagnosis of highly contagious animal epidemics].

PMID- 24091236
TI  - [Joseph Martin Meyer--one of the founders of the Swiss Society for
      Veterinarians].

PMID- 24091239
TI  - [Traffic accidents involving cats or dogs--who is liable?].

PMID- 24091240
TI  - In vivo disposition and metabolism of madecassoside, a major bioactive
      constituent in Centella asiatica (L.) Urb.
AB  - ETHNOPHARMACOLOGICAL RELEVANCE: Centella asiatica (L.) Urb. herb is frequently
      used in traditional Chinese medicine for many indications, such as traumatic
      injuries, keloid and scar. Madecassoside is the main active ingredient of this
      herb drug with higher content than other triterpenoid constituents.
      Understandings of pharmacokinetic profiles of madecassoside should be beneficial
      for its development as a therapeutic agent. MATERIALS AND METHODS: Sprague-Dawley
      rats were intravenously and orally administered madecassoside (100 mg/kg),
      respectively. Plasma, heart, liver, spleen, lung, kidney, brain, bile, urine and
      feces were collected at the designed time points. Madecassoside concentrations in
      biological samples were determined by a sensitive and well-validated liquid
      chromatography-electrospray ionization-mass spectrometry (LC-ESI-MS) method. A
      liquid chromatography coupled with time-of-flight mass spectrometry (LC-TOF-MS)
      method was established to identify its major metabolites in feces. To further
      pursue the disposition characteristics of madecassoside in rats, the involvement
      of the hepatobiliary efflux transporters in biliary elimination were studied by
      combination with digoxin (P-glycoprotein inhibitor) or probenecid (multidrug
      resistance-associated protein inhibitor). A linked-rat model was also used to
      assess the role of enterohepatic circulation in the pharmacokinetics of
      madecassoside. RESULTS: After a single oral dosing, madecassoside was widely
      distributed in heart, liver, spleen, lung and kidney of rats, and the levels of
      madecassoside in liver and kidney were relatively higher than other organs. The
      excretions of madecassoside in bile, urine and feces were 7.16% (0-12 h), 0.25%
      (0-72 h) and 24.68% (0-72 h), respectively. The findings suggested that
      madecassoside might excrete mainly by metabolites. The combination with either
      digoxin or probenecid significantly attenuated the excretion of madecassoside as
      parent from bile, indicating that P-glycoprotein and multidrug resistance
      associated protein might contribute to the hepatobiliary elimination of
      madecassoside. The presence of enterohepatic circulation, as implied by double
      humped profiles in plasma and tissue concentration-time curves, was confirmed by
      a linked-rat model. Furthermore, three metabolities of madecassoside were
      indentified in rat feces and the possible metabolic pathways were proposed.
      CONCLUSIONS: These findings provide valuable information regarding in vivo
      process of madecassoside, and help us to recognize the efficacy and safety of
      madecassoside itself, the relevant herbs or herbal preparations.

PMID- 24091242
TI  - The effect of fulvic acid on pre- and postaggregation state of Abeta17-42:
      molecular dynamics simulation studies, S. Verma, A. Singh and A. Mishra, Biochim
      Biophys Acta 1834 (2013) 24-33.

PMID- 24091241
TI  - A collaborative resource to build consensus for automated left ventricular
      segmentation of cardiac MR images.
AB  - A collaborative framework was initiated to establish a community resource of
      ground truth segmentations from cardiac MRI. Multi-site, multi-vendor cardiac MRI
      datasets comprising 95 patients (73 men, 22 women; mean age 62.73+/-11.24years)
      with coronary artery disease and prior myocardial infarction, were randomly
      selected from data made available by the Cardiac Atlas Project (Fonseca et al.,
      2011). Three semi- and two fully-automated raters segmented the left ventricular
      myocardium from short-axis cardiac MR images as part of a challenge introduced at
      the STACOM 2011 MICCAI workshop (Suinesiaputra et al., 2012). Consensus
      myocardium images were generated based on the Expectation-Maximization principle
      implemented by the STAPLE algorithm (Warfield et al., 2004). The mean
      sensitivity, specificity, positive predictive and negative predictive values
      ranged between 0.63 and 0.85, 0.60 and 0.98, 0.56 and 0.94, and 0.83 and 0.92,
      respectively, against the STAPLE consensus. Spatial and temporal agreement varied
      in different amounts for each rater. STAPLE produced high quality consensus
      images if the region of interest was limited to the area of discrepancy between
      raters. To maintain the quality of the consensus, an objective measure based on
      the candidate automated rater performance distribution is proposed. The consensus
      segmentation based on a combination of manual and automated raters were more
      consistent than any particular rater, even those with manual input. The consensus
      is expected to improve with the addition of new automated contributions. This
      resource is open for future contributions, and is available as a test bed for the
      evaluation of new segmentation algorithms, through the Cardiac Atlas Project
      (www.cardiacatlas.org). 

PMID- 24091243
TI  - Neonaticide in India and the stigma of female gender: report of two cases.
AB  - Neonaticide is known to occur across the globe in both developed and developing
      countries, but has rarely been reported from India. Two similar cases of female
      neonaticide are presented which were committed by their mothers while in the
      maternity ward. The social issues and maternal provocation highlighted in this
      report are different from those reported in world reviews of neonaticide. 

PMID- 24091244
TI  - Microsporidia: diverse, dynamic, and emergent pathogens in aquatic systems.
AB  - Microsporidia cause important diseases in aquatic organisms. Susceptible hosts
      span a remarkable taxonomic spectrum, from protists to mammals. Known genera
      represent a small fraction of extant taxa in global aquatic systems. Transmitting
      horizontally or vertically, effects range from cryptic to catastrophic;
      individual level effects being extrapolated to populations and ecosystems. Debate
      over positioning within the eukaryotes and internal structuring of the phylum has
      benefited from molecular phylogenetic approaches to taxonomy. Similar tools offer
      new perspectives on transmission between hosts of differing trophic status and
      habitats. Accessible models for host-pathogen interaction are emerging from full
      genome sequencing projects. Hyperparasitism and the close phylogenetic
      relationship between taxa infecting invertebrates and vertebrates not only
      underline a ubiquity in aquatic systems but also potential for zoonotic transfer.

PMID- 24091245
TI  - Recovery discrepancies of OH-PBDEs and polybromophenols in human plasma and cat
      serum versus herring and long-tailed duck plasma.
AB  - Hydroxylated polybrominated diphenyl ethers (OH-PBDEs) have been identified as
      metabolites of polybrominated diphenyl ethers (PBDEs) and/or as natural products.
      The OH-PBDEs and polybromophenols have come into focus over the last decade due
      to their abundance in biota and their potential adverse health effects. The
      present recovery study aims to validate a commonly used method (published by
      Hovander et al. 2000) for OH-PBDE analysis in human plasma. Further, the authors
      intended to determine the method's applicability to serum/plasma matrices from
      other species than humans. The investigated matrices were human plasma, cat
      serum, herring- and long-tailed duck plasma. The recovery study included nine OH
      PBDEs, four polybromophenols and three methoxylated PBDEs (MeO-PBDEs). Five
      replicates of each matrix were spiked with these compounds at two dose levels; a
      low dose (0.5 ng) and a high dose (5 ng) and were cleaned up according to the
      Hovander method. The recovery of OH-PBDEs and polybromophenols in human plasma
      and cat serum were high and reproducible at both dose levels whereas the recovery
      for herring and long-tailed duck plasma were low and insufficient with great
      variability amongst OH-PBDE congeners at both dose levels. Our data show that the
      method can be fully applied to matrices like human plasma and cat serum but not
      for herring and long-tailed duck plasma without further method development. Hence
      care needs to be taken when applying the method onto other blood matrices without
      validation since the present study have demonstrated that the recoveries may
      differ amongst OH-PBDE congeners and specie.

PMID- 24091246
TI  - Distribution of environmentally sensitive elements in residential soils near a
      coal-fired power plant: potential risks to ecology and children's health.
AB  - One hundred and twelve soil samples were collected from residential areas
      surrounding a coal-fired power plant at Huainan City, Anhui Province, China. The
      concentrations of environmentally sensitive elements (ESEs As, Cd, Cr, Cu, Hg,
      Mn, Ni, Pb, V and Zn) in soil samples were determined, and their potential
      ecological and health risks were assessed. Mean concentrations of ESEs in the
      downwind soils of the power plant are relatively higher than those in the upwind
      soils, pointing to a potential ESEs input from coal combustion. The calculated
      ecological risk of ESEs in soils indicates a relatively low ecological risk.
      Hazard quotient (HQ) of ESEs in downwind soils is 1.5, suggesting a potential
      health risk for children. However, the carcinogenic risk values of ESEs in soils
      are within the acceptable non-hazardous range of 1E-06-1E-04. 

PMID- 24091247
TI  - Investigation on mechanism of Cr(VI) reduction and removal by Bacillus
      amyloliquefaciens, a novel chromate tolerant bacterium isolated from chromite
      mine soil.
AB  - A strain CSB 9 isolated from chromite mine soil of Sukinda, India was identified
      as Bacillus amyloliquefaciens based on biochemical and 16S rRNA gene sequencing.
      The strain exhibited relatively high tolerance to Cr(VI) (?900mgL(-1)) and fast
      reduction rate of 2.22mg Cr(VI) L(-1)h(-1), under optimized conditions of 100mgL(
      1) Cr(VI), pH 7 and temperature 35 degrees C within 45h. Mechanism of Cr(VI)
      reduction as well as nature and fate of the reduced product were studied to
      determine the scope of removal of reduced Cr(III) end product. AAS analyses of
      the culture products treated with Cr(VI) for 45h showed the distribution of
      Cr(III) in pellet and culture supernatant to be 37.4+/-1.7 and 62.6+/-3.4mgL(-1),
      respectively. In SEM images, the bacterial pellets with Cr(VI) treatment appeared
      coagulated, rough and porous whereas the pellets without Cr(VI) treatment
      appeared regular, smooth and non-porous in structure. SEM-EDX of the bacterial
      precipitates under Cr(VI) treatment revealed immobilization of Cr(III) species on
      the bacterial cell surface. Further Raman spectroscopy analysis confirmed the
      presence of Cr(III) species, with characteristic peak at around 600cm(-1). TEM
      EDX study of the bacterial precipitates under Cr(VI) treatment showed
      intracellular deposition of Cr(III) which are in nanometric range. Further
      characterization of reduced product by XRD, FT-IR and SAED analyses suggested the
      formation of poorly crystalline end products. A Cr(VI) removal mechanism
      considering both the surface immobilization and intracellular accumulation of
      Cr(III) along with the formation of coagulated cell precipitate by living B.
      amyloliquefaciens was suggested. 

PMID- 24091248
TI  - Effects of gait speed on stability of walking revealed by simulated response to
      tripping perturbation.
AB  - The objective of this work was to study stability of walking over a range of gait
      speeds by means of muscle-driven simulations. Fast walking has previously been
      related to high likelihood of falling due to tripping. Various measures of
      stability have shown different relationships between walking speed and stability.
      These measures may not be associated with tripping, so it is unclear whether the
      increase in likelihood of falling is explicable by an increase in instability.
      Here, stability with respect to a constant tripping perturbation was quantified
      as the immediate passive response of torso to the perturbation. Subject-specific
      muscle-driven simulations of eight young healthy subjects walking at four speeds,
      created by combining a generic musculoskeletal model with gait data, were
      analyzed. In the simulations, short perturbations were performed several times
      throughout the swing-phase by applying a constant backward force to the swing
      foot of the model. Maxima of changes in the torso (angular) velocity components
      during the swing-phase were studied. These changes in the velocity components
      correlated with the walking speed as follows: anterior-posterior r=0.37 (p<0.05),
      vertical r=0.41 (p<0.05), and medio-lateral r=-0.40 (p<0.05). Of the angular
      velocity components, only the vertical component correlated statistically
      significantly with speed, r=0.52 (p<0.01). The weak and varying speed effects
      suggest that fast walking is not necessarily more unstable than slow walking, in
      the sense of response to a constant perturbation. 

PMID- 24091249
TI  - Ellipse area calculations and their applicability in posturography.
AB  - The quantification of postural sway is considered to be an essential part of
      posturography and is important for research and clinical utility. A widely used
      method to calculate the scatter of center of pressure data is an ellipse that
      encloses about 100(1-alpha)% of the observations. However, underlying definitions
      and terminologies have been misused in many cases. Hence, outcomes of different
      studies are proved to be incommensurable. In order to attain inter-study
      comparability, standardization of calculation methods has to be advanced. This
      work features a comprehensive and consistent overview of the methods for elliptic
      area approximation contrasting general principles of confidence and prediction
      regions. As a result, we recommend the usage of the prediction ellipse, as far as
      we demonstrate that confidence ellipses emerge to be inappropriate for
      posturographic scatter evaluation. Furthermore, we point at problems that come
      along with different sample sizes. 

PMID- 24091250
TI  - Effect of treadmill training based real-world video recording on balance and gait
      in chronic stroke patients: a randomized controlled trial.
AB  - OBJECTIVE: The purpose of this study was to determine the role of treadmill
      training based real-world video recording (TRWVR) for balance and gait ability in
      chronic stroke patients. DESIGN: Thirty chronic stroke patients were randomly
      assigned to either the TRWVR group (n=15) or the control group (n=15). Both
      groups participated in a standard rehabilitation program; in addition, the TRWVR
      group participated in TRWVR for 30 min per day, three times per week, for 6
      weeks, and the control group participated in treadmill walking training for 30
      min per day, three times per week, for 6 weeks. Balance ability was measured
      using the Berg Balance Scale (BBS), Timed Up and Go test (TUG) and the postural
      sway by force platform system. Gait performance was measured using a pressure
      sensitive walkway. RESULTS: Significant differences in the time factor for
      dynamic balance and gait (P<0.05) were observed in the TRWVR and control group,
      with the exception of static balance. For the group * time interaction,
      significant improvements in dynamic balance and gait (P<0.05). In the correlation
      coefficient, no significant correlation was observed between changes in postural
      sway and other dependent variables. CONCLUSIONS: Findings of this study
      demonstrated that the real-world video recording has an effect on dynamic balance
      and gait in chronic stroke patients when added to treadmill walking.

PMID- 24091251
TI  - Resveratrol exacerbates both autoimmune and viral models of multiple sclerosis.
AB  - The polyphenol compound resveratrol is reported to have multiple functions,
      including neuroprotection, and no major adverse effects have been reported.
      Although the neuroprotective effects have been associated with sirtuin 1
      activation by resveratrol, the mechanisms by which resveratrol exerts such
      functions are a matter of controversy. We examined whether resveratrol can be
      neuroprotective in two models of multiple sclerosis: experimental autoimmune
      encephalomyelitis (EAE) and Theiler's murine encephalomyelitis virus-induced
      demyelinating disease (TMEV-IDD). EAE was induced in C57BL/6 mice, which were fed
      a control diet or a diet containing resveratrol during either the induction or
      effector phase or through the whole course of EAE. SJL/J mice were infected with
      TMEV and fed a control diet or a diet containing resveratrol during the chronic
      phase of TMEV-IDD. In EAE, all groups of mice treated with resveratrol had more
      severe clinical signs than the control group. In particular, resveratrol
      treatment during the induction phase resulted in the most severe EAE, both
      clinically and histologically. Similarly, in the viral model, the mice treated
      with resveratrol developed significantly more severe TMEV-IDD than the control
      group. Thus, surprisingly, the resveratrol treatment significantly exacerbated
      demyelination and inflammation without neuroprotection in the central nervous
      system in both models. Our findings indicate that caution should be exercised in
      potential therapeutic applications of resveratrol in human inflammatory
      demyelinating diseases, including multiple sclerosis. 

PMID- 24091252
TI  - Glycemic control in young children with diabetes: the role of parental health
      literacy.
AB  - OBJECTIVE: This cross sectional study examined the relationship between parental
      health literacy (HL), diabetes related numeracy, and parental perceived diabetes
      self-efficacy on glycemic control in a sample of young children with Type 1 DM.
      METHODS: Seventy primary caregivers of children (age 3-9 years) with Type 1 DM
      were recruited and surveyed at diabetes outpatient clinic visits. Patients'
      medical histories were obtained by medical chart review. RESULTS: Parental
      diabetes related numeracy (r=-.52, p<01), but not reading skills (r=-.25, p=NS)
      were inversely correlated with the child's glycemic control (HbA1c). Parental
      perceived diabetes self-efficacy was also negatively correlated to their child's
      HbA1c (r=-.47, p<01). When numeracy and parental perceived diabetes self-efficacy
      were included as predictors of HbA1c, the model was significant (F=12.93, p<.01)
      with both numeracy (beta=-.46, p<.01) and parental perceived diabetes self
      efficacy (beta=-.36, p=.01) as significant predictors of HbA1c. CONCLUSIONS: Data
      from this study highlight the importance of considering the role of parental
      numeracy, in health outcomes for children with Type 1 DM. PRACTICE IMPLICATIONS:
      Practitioners should assess parental health literacy and consider intervention
      when needed.

PMID- 24091253
TI  - Abundance and persistence of antibiotic resistance genes in livestock farms: a
      comprehensive investigation in eastern China.
AB  - Increases of antibiotic resistance genes in the environment may pose a threat to
      public health. The purpose of this study was to investigate the abundance and
      diversity of tetracycline (tet) and sulfonamide (sul) resistance genes in eight
      livestock farms in Hangzhou, eastern China. Ten tet genes (tetA, tetB, tetC,
      tetG, tetL, tetM, tetO, tetQ, tetW, and tetX), two sul genes (sulI and sulII),
      and one genetic element associated with mobile antibiotic resistance genes [class
      1 integron (intI1)] were quantified by real-time polymerase chain reaction. No
      significant difference was found in the abundance of the tet and sul genes in
      various scales of pig, chicken, and duck farms (P>0.05). The average abundance of
      ribosomal protection protein genes (tetQ, tetM, tetW, and tetO) in the manure and
      wastewater samples was higher than most of the efflux pump genes (tetA, tetB,
      tetC, and tetL) and enzymatic modification gene (tetX) (P<0.05), except for
      efflux pump gene tetG, which was abundant and showed no difference from tetM.
      Most ARGs had higher relative abundance in the wastewater lagoon than in manures
      even after treatment. Although the three ribosomal protection protein genes
      (tetQ, tetW, and tetO) had higher relative abundance, numbers were reduced during
      the complete wastewater treatment process in pig farms (P<0.05). The relative
      abundance of tetG, sulI, and sulII increased after the wastewater treatment and
      the removal of these three genes exhibited significant positive correlations with
      the intI1 gene (tetG: R(2)=0.60, P<0.05; sulI: R(2)=0.72, P<0.05; sulII:
      R(2)=0.62, P<0.05), suggesting that intI1 may be involved in their proliferation.
      As for tetM and sulII genes, a highly significant difference was found in manure
      samples between pig farms and duck farms (P<0.001). Phylogenetic analysis showed
      that tetM was more diverse in duck farms than in pig farms. Additionally, sulII
      sequence was conserved both in pig and duck farms. This is the first
      comprehensive study to detail the relative abundance of specific ARGs in animal
      manures and agricultural wastewater treatment systems, potentially providing
      knowledge for managing antibiotic resistance emanating from agricultural
      activities. 

PMID- 24091254
TI  - Serum concentrations of polybrominated diphenyl ethers (PBDEs) and a
      polybrominated biphenyl (PBB) in men from Greenland, Poland and Ukraine.
AB  - Many brominated flame retardants (BFRs)-including polybrominated diphenyl ethers
      (PBDEs)-have been shown to persist in the environment, and some have been
      associated with adverse health effects. The aim of the present study was to
      quantify serum concentrations of common brominated flame retardants in Inuit men
      from across Greenland, and in men from Warsaw, Poland and Kharkiv, Ukraine. Serum
      was sampled between 2002 and 2004 from men 19 to 50years of age. 299 samples were
      analyzed for BDE-28, 47, 99, 100, 153, 154 and 183 and the brominated biphenyl BB
      153 using gas chromatography-high resolution mass spectrometry. BDE-47 and BDE
      153 were detected in more than 95% of samples from all three populations. All
      other congeners, except BDE-154, were detected in more than 70% of samples from
      Greenland; lower detection frequencies were observed in Polish and Ukrainian
      samples. Concentrations of individual congeners were 2.7 to 15 fold higher in
      Greenlandic relative to Polish and Ukrainian men. Geometric mean concentrations
      of the sum of the most abundant PBDEs of the Penta-BDE commercial mixture (BDE
      47, 99, 100, 153 and 154) were 6.1, 1.7 and 0.87ng/g lipids in the Greenlandic,
      Polish and Ukrainian men, respectively. Furthermore, significant geographical
      differences in BFR concentrations were observed within Greenland. Principal
      component analysis revealed distinct clustering of samples by country of origin.
      The associations between SigmaPBDEs and age were inconsistent, varying from no
      association in Greenlandic and Polish study populations to a U-shaped
      relationship in Ukrainians. We report BFR levels for three populations for which
      sparse biomonitoring data exists. 

PMID- 24091255
TI  - Psychiatric evaluations for individuals requesting assisted death in Washington
      and Oregon should not be mandatory.

PMID- 24091257
TI  - The use of cannabis for management of chronic pain.

PMID- 24091258
TI  - Psychiatric review should be mandatory for patients requesting assisted suicide.

PMID- 24091259
TI  - Surgical treatment of clavicular fractures in Finland - A register based study
      between 1987 and 2010.
AB  - BACKGROUND: Clavicle fractures are among the most common upper extremity
      injuries. Traditionally most clavicle fractures have been treated non-surgically,
      but during recent decades the surgical treatment of clavicle fractures has
      increased. The purpose of this study was to assess the numbers and trends of
      surgically treated clavicle fractures in Finland between 1987 and 2010. METHODS:
      The study covered the entire adult (>18 years) population of Finland over the
      study period. Data on surgically treated clavicle fractures was collected from
      the Finnish National Hospital Discharge Register. We assessed the number and
      incidence of surgically treated clavicle fractures annually. RESULTS: A total of
      7073 surgically treated clavicle fractures were identified in the register over
      the study period. Three-fourths of the surgically treated patients were men and
      one-fourth was women. The incidence of surgical treatment increased nearly
      ninefold from 1.3 per 100,000 person years in 1987 to 10.8 per 100,000 person
      years in 2010. The increase in the rate of surgical treatment was especially
      notable in men. CONCLUSIONS: A striking increase in incidence of surgically
      treated clavicle fractures was seen from 1987 to 2010. Although the actual
      incidence of clavicle fractures is not known, we assume that the proportion of
      patients receiving surgical treatment has increased markedly without high-quality
      evidence. Since recent reports have suggested similar functional results between
      operative and conservative treatment critical evaluation of the treatment policy
      of clavicle fractures is warranted.

PMID- 24091260
TI  - [Pancreatic head mass in chronic pancreatitis].

PMID- 24091261
TI  - [The clinical analysis of a step-up approach for severe acute pancreatitis:
      report of 121 cases].
AB  - OBJECTIVE: To investigate the feasibility and clinical value of the step-up
      approach for severe acute pancreatitis (SAP). METHODS: Clinical data of 121 SAP
      patients admitted between January 2002 and December 2011 were retrospectively
      analyzed. Fifty-eight patients (37 males and 21 females, aged from 20 to 72
      years, mean 47.6 years) in the group of direct open necrosectomy from January
      2002 to December 2006 were performed laparotomy through removal of all necrotic
      tissue. Sixty-three patients (42 males and 21 females, aged from 19 to 78 years,
      mean 46.2 years) of step-up approach from January 2007 to December 2011 underwent
      percutaneous catheter drainage through retroperitoneum or omental bursa guided by
      B-type ultrasonography for the first therapy, and then, according to the
      pathogenetic condition, if necessary, followed by a small incisional necrosectomy
      along the drainage tube. The two groups were compared for the rates of
      postoperative complications, death, transfusion and length of stay, medical
      costs. RESULTS: The rates of total postoperative complications, organ
      dysfunction, alimentary tract fistula and incisional hernia in step-up approach
      group were significantly lower than those of direct open necrosectomy group
      (31.7% vs. 62.1%, 14.3% vs. 37.5%, 6.3% vs. 19.0%, 9.5% vs. 29.3%; chi(2) = 4.43
      to 11.17, P = 0.001 to 0.035). The other complications had no significant
      differences between the two groups (P > 0.05). Patients in step-up approach group
      had a lower rates of transfusion (44.4% vs. 70.7%, chi(2) = 8.488, P = 0.004),
      fewer medical costs of transfusion and hospital stay, compared with those in
      direct open necrosectomy group ((2525 +/- 4573) yuan vs. (4770 +/- 6867) yuan, t
      = 2.131, P = 0.035; (171 213 +/- 50 917) yuan vs. (237 874 +/- 67 832) yuan, t =
      2.496, P = 0.014). There were no significant differences of length of stay and
      mortality between two groups (P > 0.05). CONCLUSION: Step-up approach for SAP
      which can reduce the rates of postoperative complications, transfusion and
      medical costs has significant feasibility and great clinical value.

PMID- 24091262
TI  - [Analysis and management of the biliary complications after liver
      transplantations].
AB  - OBJECTIVE: To discuss the relevant factors of biliary complications after liver
      transplantation and to investigate the value of comprehensive management for the
      complications. METHODS: The data of 366 patients undergoing liver transplantation
      from October 2000 to March 2012 was analyzed retrospectively, and the risk
      factors were analyzed by univariate analysis and Stepwise Logistic regression.
      The cases with biliary leak were administered thorough drainage. The cases with
      anastomotic biliary stricture were administered sacculus dilatation through
      percutaneous transhepatic cholangiography (PTC) and endoscopicretrograde
      cholangiopancreatography (ERCP). If necessary, some cases were placed biliary
      tract brackets. The patients with nonanastomotic biliary stricture were treated
      with PTC plus choledochoscope. RESULTS: All the 366 patients were followed up for
      58.5 (10 to 129) months. Biliary complications after liver transplantation were
      diagnosed in 42 cases among these patients. The incidence for biliary
      complications was 11.5%. The univariate analysis and multivariate Logistic
      regression analysis showed that the second warm ischemia period and the blood
      loss and the damage of blood supply and the diameter of biliary anastmosis were
      significantly associated with biliary complications after liver transplantations
      (Wald = 9.474 to 17.208, P < 0.05). Twelve cases with biliary leak were cured
      through abdominal and nasobiliary drainage. Twenty-two cases with anastomotic
      biliary stricture were administered sacculus dilatation through ERCP or PTC and
      were cured, including 6 cases were placed biliary tract brackets. Among 8 cases
      with nonanastomotic biliary stricture, 6 cases were cured through PTC associating
      with choledochoscope. One case was treated second liver transplantation and
      another case got worse. CONCLUSIONS: Ischemic injury and the diameter of
      anastmosis are risk factors for biliary complications after liver
      transplantations. The interventional management of biliary stricture and bile
      leakage after liver transplantation is safe and effective.

PMID- 24091263
TI  - [New method to predict cerebral hyperperfusion syndrome after carotid
      endarterectomy by transcranial Doppler].
AB  - OBJECTIVE: To determine the diagnostic value for predicting cerebral
      hyperperfusion syndrome (CHS) by adding a transcranial Doppler (TCD) measurement
      at the end of the carotid endarterectomy (CEA) at the operating room. METHODS:
      Patients who underwent CEA between August 2009 and December 2011 of the
      prospective clinical trial in whom both intra- and post-operative TCD monitoring
      were performed were included. The middle cerebral artery velocities pre-clamping,
      post-declamping and post-operatively were measured by TCD. The intra-operative
      velocity increase ratio (VR1) was compared to the postoperative velocity increase
      ratio(VR2) in relation to CHS by calculating the sensitivity,specificity,
      positive predictive value, negative predictive value. The receiver operating
      characteristic curve (ROC) were also performed. The area under the curve (AUC) of
      ROC of VR1 and VR2 were compared.All the data were analyzed using SPSS 20.0
      software. RESULTS: VR1 > 100% was identified in 6 patients, while VR2 > 100% was
      identified in 18 patients, respectively. Ten patients were diagnosed with CHS.
      The AUC of VR2 (0.728) was higher than AUC of VR1 (0.636). The best fit cutoff
      point of VR2 was 100%. The sensitivity, specificity, positive predictive value,
      negative predictive value were 70%, 83%, 39%, 95%, respectively, which
      demonstrates a better predictive power than VR1. CONCLUSION: Besides the commonly
      used intra-operative TCD monitoring, additional TCD measurement at the end of the
      carotid endarterectomy at the operating room is more useful to more accurately
      predict CHS.

PMID- 24091264
TI  - [Comparative study of Kurokawa's double door laminoplasty and modified Kurokawa's
      double door laminoplasty for the treatment of cervical disorders].
AB  - OBJECTIVE: To observe and compare the medium-long-term efficacy of Kurokawa's and
      modified Kurokawa's double door laminoplasty for the treatment of cervical
      disorders. METHODS: A retrospective analysis was performed to compare the
      outcomes and complications between two kinds of operations on 172 cases from
      January 2002 to December 2010, including 106 cases of cervical spondylotic
      myelopathy, 52 cases of cervical stenosis, 21 cases of cervical ossification of
      the posterior longitudinal ligament. Patients were divided into two groups
      according to two surgical methods: traditional group, including 51 male and 18
      female patients, with mean age of (56 +/- 18) years (35-76 years); modified
      group, including 75 male and 28 female patients, with mean age of (58 +/-
      20)years (35-80 years). The two groups were comparable and compared according to
      different data using t test, chi(2) test and rank sum test. RESULTS: All patients
      were followed up continuously for (52 +/- 33)months, 123 patients were followed
      up >= 2 years, 71 patients >= 5 years. All patients' Japanese Orthopaedic
      Association (JOA) score improved significantly at the latest follow-up(t = 3.420,
      P < 0.01); no significant difference between the patients' JOA score improvement
      rate of two groups. The postoperative incidence rate of axial symptoms in
      patients of modified group (3.9%) was significantly lower than the traditional
      group (14.5%) (chi(2) = 7.548, P < 0.05), and cervical intervertebral activity
      decreased in the modified group was better than the traditional group in the
      first 3 months postoperatively (27% +/- 6% vs. 19% +/- 4%,Z = 6.34, P < 0.05),
      but during the medium-long-term follow-up, no significant difference in the
      cervical intervertebral activity decreased between two groups. CONCLUSIONS:
      Medium-long-term efficacy of Kurokawa's and modified Kurokawa's double door
      laminoplasty is satisfied and reliable. Avoiding damaging of semispinalis
      cervicis insertion in spinous process of C2, the modified operation method can
      protect the extensor group of the neck muscle and reduce the incidence of
      postoperative axial symptoms better.

PMID- 24091265
TI  - [Radiological characteristics of leg length discrepancy and knee varus/valgus
      deformity among unilateral developmental hip dislocation patients].
AB  - OBJECTIVE: To observe the leg length discrepancy and accompanied knee
      varus/valgus deformity in matured patients with unilateral dislocation of the
      hip. METHODS: From March 2011 to December 2012, 28 patients who had unilateral
      dislocation of hip (Hartofilakidis classification II 17 cases and III 11 cases)
      were involved in this study.There were 6 male patients and 22 female patients,
      the age of the patients were 13.4-66.2 years, with mean age of 29.8 years. The
      standing anteroposterior full leg length X-ray films were obtained. Leg length
      discrepancy, the length of the femur, the length of the tibia and identified the
      varus/valgus knee deformities were measured. Statistical analysis was performed.
      A student's t test for paired samples was done for comparison of the parameters
      in the same patient between dislocated and undislocated leg, and the chi(2) test
      were used to assess valgus and varus knees, leg length discrepancy in high
      dislocation and low dislocation groups. RESULTS: Seventeen (60.7%) cases had
      longer femur length on the dislocated side than that on the undislocated side (t
      = 1.328, P = 0.197), with the maximum lengthening of 32.7 mm and a mean
      lengthening of 9.5 mm. Twenty-one (75.0%) cases had longer tibia length on the
      dislocated side (t = 3.039, P = 0.006), with a maximum lengthening of 10.9 mm and
      a mean lengthening of 4.5 mm. Twenty (71.4%) cases had longer relative leg length
      on the dislocated side (t = 2.451, P = 0.022), with a maximum lengthening of 25.0
      mm and a mean lengthening of 9.4 mm. On the dislocated side of the leg, the
      degree of valgus angle was 3 degrees  +/- 4 degrees ,while on the undislocated
      side, that was -3 degrees  +/- 4 degrees (t = 5.642, P = 0.000). On the
      dislocated side, 12 cases (42.9%) were of valgus deformities and 1 case was of
      varus deformity. On the contralateral side, 15 cases of varus deformities (53.6%)
      and 1 case of valgus deformity were observed(chi(2) = 18.139,P = 0.000).
      CONCLUSIONS: Most dislocated legs are longer in length than the contralateral
      side, both femur and tibia have also lengthened accordingly. Many knees on the
      dislocated side present valgus deformity, half of the knees on the contralateral
      side present varus deformity.

PMID- 24091266
TI  - [Relationship of iron overload to bone mass density and bone turnover in
      postmenopausal women with fragility fractures of the hip].
AB  - OBJECTIVE: To study relationships between serum ferritin and bone metabolism in
      patients with hip fragility fractures. METHODS: This cross-sectional study
      included 76 postmenopausal women with hip fracture from Feburary 2011 to June
      2012. The mean age of the women was (73 +/- 10) years (range, 55-93 years) and
      the mean duration of menstruation was (22 +/- 10)years (range, 5-50 years). Serum
      concentrations of ferritin, transferrin, alkaline phosphatase (ALP), amino
      terminal extension peptide of type I collagen (P1NP), C-terminal telopeptides of
      type I collagen (beta-CTX)and femoral and lumbar bone mineral density by dual
      energy X-ray absorptiometry were measured. Bone metabolism was compared between
      normal and elevated ferritin groups with t-test, Pearson linear, partial
      correlation and multiple regression analysis examined associations between iron-
      and bone-related markers. RESULTS: Serum ferritin concentration raised to (230 +/
      146)ug/L, transferrin concentration reduced to (1.89 +/- 0.33)g/L. P1NP
      concentration raised to (61 +/- 32) ng/L when the concentration of serum ALP and
      beta-CTX were in the normal range. T-scores for bone mineral density in the
      femoral neck (-2.0 +/- 1.1) and lumbar (-2.1 +/- 1.2) were below the normal
      ranges(-1.0-1.0). The subjects were divided into two groups according to serum
      ferritin concentration, normal group(serum ferritin concentration <= 150 ug/L, n
      = 25) and elevated group(serum ferritin concentration > 150 ug/L, n = 51).
      Patients of elevated group had lower bone mineral density in femoral neck and
      lumbar than normal group(t = 3.13,2.89, P < 0.01), and higher P1NP, beta-CTX
      concentration (t = -2.38, -3.59, P < 0.05) . In partial correlation analysis
      adjusted for confounders, serum ferritin concentration was correlated negatively
      with bone mineral density in both femoral neck and lumbar (r = -0.335,-0.295, P <
      0.05), and positively with P1NP and beta-CTX (r = 0.467,0.414, P < 0.05), but not
      correlated with ALP (r = 0.188, P > 0.05). Transferrin concentration tended to be
      correlated positively with bone mineral density in both femoral neck and lumbar
      (r = 0.444, 0.262, P < 0.05) and negatively with ALP, P1NP and beta-CTX(r = 
      0.326,-0.285,-0.278, P < 0.05). CONCLUSIONS: Iron overload has a high prevalence
      in postmenopausal women with fragility fracture. Increased iron stores, which
      might lead to bone loss and lower bone mineral density by enhancing the activity
      of bone turnover, could be an independent factor to take effects on bone
      metabolism on postmenopausal women.

PMID- 24091267
TI  - [Preliminary study for classification of spino-pelvic sagittal alignment in adult
      volunteers].
AB  - OBJECTIVE: To investigate the feasibility of the classification of the spino
      pelvic sagittal alignment in adluts according to lumbar lordosis (LL) and
      inflection point (IP). METHODS: Whole spine, standing radiographs of 223 adult
      volunteers were taken from July to August in 2011 .There were 111 cases(56 female
      and 55 male) enrolled in the study based on the inclusion criteria. The pelvic
      and spinal parameters, including thoracic kyphosis(TK), thoracolumbar
      kyphosis(TLK), LL, sacral slope(SS), pelvic tilt(PT), pelvic incidence(PI),
      intervertebral endplate angle, sagittal vertical axis (SVA), spino-sacral angle
      (SSA) and IP were measured. The spino-pelvic sagittal alignment were classified
      in to 3 types according to LL and IP. Type I: LL > -40 degrees , IP located below
      L2 ~ 3; Type II: -60 degrees  <= LL <= -40 degrees , IP located in L1 ~ 2 or T12
      ~ L1; Type III: LL < -60 degrees , P located above T11 ~ 12. Pearson correlation
      analysis was used to test the correlation between the variables. The parameters
      in each type were compared by oneway-ANOVA respectively,then additional multiple
      comparisons were performed. RESULTS: The mean value of LL was -49 degrees  +/- 10
      degrees , TK was 36 degrees  +/- 7 degrees , TLK was 6 degrees  +/- 7 degrees ,
      PT was 11 degrees  +/- 7 degrees , SS was 34 degrees  +/- 8 degrees , PI was 45
      degrees  +/- 9 degrees , SSA was 127 degrees  +/- 9 degrees  and SVA was (-2.7 +/
      22.8)mm, respectively. Only LL had significant statistical correlation with all
      the other parameters. Negative correlation presented between LL and TK, PI, SS,
      SSA (r = -0.387, -0.536, -0.858, -0.801,P < 0.05). Positive correlation presented
      between LL and TLK, SVA, PT (r = 0.319, 0.296, 0.262, P < 0.05). All the
      volunteers were classified into the 3 types: Type I1 9 cases, Type II 75
      cases,Type III 17 cases. Oneway-ANOVA results showed statistical difference in
      LL, TK, TLK, PT, SS, PI, SSA, SVA among the 3 types, (F = 164.559, 7.431, 14.099,
      4.217, 53.856, 6.252, 35.995, 8.626, P < 0.05 ). Multiple comparisons showed that
      LL, SS, SSA, PI had statistical difference between each two types comparison (P <
      0.05). CONCLUSIONS: LL is the central parameter of the spino-pelvic sagittal
      balance. The patterns of the spino-pelvic sagittal alignment in adults could be
      classified into three types, according to LL and IP. The classification could
      describe the morphological differences and balance of the spino-pelvic sagittal
      alignment.

PMID- 24091268
TI  - [Effectiveness and safety of tranexamic acid in patients receiving on-pump
      coronary artery bypass grafting without clopidogrel and aspirin cessation].
AB  - OBJECTIVE: To evaluate the effectiveness and safty of tranexamic acid in patients
      receiving on-pump coronary artery bypass grafting (CABG) without clopidogrel and
      aspirin cessation. METHODS: The current study is a prospective, randomized and
      placebo-control trial. A total of 116 patients receiving selective on-pump CABG
      with their last ingestion of clopidogrle and aspirin within 7 days preoperatively
      were recruited. Despite 6 patients withdrawal their consent, the rest 110 were
      randomized to receive tranexamic acid or placebo. The tranexamic acid regimen was
      a bolus of 10 mg/kg followed by a maintenance of 10 mg.kg(-1).h(-1) throughout
      the surgery. The primary outcome was the volume of allogeneic erythrocyte
      transfused perioperatively. RESULTS: Baseline characteristics were comparable
      between the groups. In patients receiving tranexamic acid and placebo
      respectively, the volume of allogeneic erythrocyte transfused was 4.0 (7.5) units
      and 6.0(6.0) units (W = 1021, P < 0.01). In these 2 groups respectively, blood
      loss was 930 (750) ml and 1210 (910) ml (W = 1042, P < 0.01), the incidence of
      major bleeding was 50.9% and 76.4% (chi(2) = 7.70, P < 0.01), the incidence of
      reoperation was 0 and 9.1% (chi(2) = 5.24, P = 0.02); the volume of plasma
      transfused was 400 (600) ml and 600 (650) ml (W = 1072, P = 0.01), the exposure
      of plasma was 60.0% and 85.5% (chi(2) = 8.98, P < 0.01) and the exposure to any
      allogeneic blood products was 85.5% and 98.2% (chi(2) = 5.93, P = 0.01).
      Perioperative mortality, morbidity and the incidence of adverse events were
      balanced between the groups without statistical significance. CONCLUSION:
      Tranexamic acid reduced significantly postoperative bleeding and transfusion in
      patients receiving on-pump CABG without clopidogrel and aspirin cessation.

PMID- 24091269
TI  - [Early removal of the chest tube after lobectomies: a prospective randomized
      control study].
AB  - OBJECTIVE: To evaluate the feasibility and safety of early chest tube removal
      after lobectomies for lung diseases. METHODS: A prospective randomized control
      study was performed with data collected from lobectomies between March 2012 and
      September 2012. Eligible patients (n = 70) were randomized into two groups; early
      removal group (removal of chest tube when drainage less than 300 ml/24 h, n = 41)
      and traditional management group (removal of chest tube when drainage less than
      100 ml/24 h, n = 29). Criteria for early removal were established and met before
      chest tube removal. The volume and character of drainage, time of extracting
      drainage tube and postoperative hospital stay were measured. All patients
      received standard care during hospital admission and a follow-up visit was
      performed after 7 days of discharge from hospital. RESULTS: There were no
      differences between two groups with respect to age, sex, comorbidities, or
      pathologic evaluation of resection specimens. The median volume of drainage
      within 24 h after surgery was 300 ml and within 48 h was 250 ml, there was
      significantly different between two groups (Z = -2.059, P = 0.039). Patients
      undergoing early removal management had a shorter Chest tube duration (44 hours
      vs. 67 hours, Z = -2.914, P = 0.004) and a shorter postoperative hospital stay
      (5.0 days vs. 6.0 days, Z = -3.882, P = 0.000). Analysis of data showed no
      statistically significant differences between the rate of pleural effusions
      developed, thoracentesis and complications, one week after discharge from
      hospital. CONCLUSIONS: Compared to the traditional management group (drainage <=
      100 ml/24 h), early removal of chest tube after lobectomy (drainage <= 300 ml/24
      h) is feasible and safe. It could result in a shorter hospital stay, and most
      importantly, reduces morbidity without the added risk of complications.

PMID- 24091270
TI  - [Prognostic significance of the 2004 WHO classification compared with the 1973
      WHO classification for organ-confined invasive bladder cancer].
AB  - OBJECTIVE: To compare the 2004 and 1973 WHO classifications for predicting tumor
      recurrence for organ-confined (T stage <= pT2b) invasive urothelial carcinoma of
      the bladder treated with radical cystectomy. METHODS: From February 2000 to
      August 2011, the 173 consecutive cases of organ-confined invasive urothelial
      carcinoma of the bladder were treated with radical cystectomy. The data of
      clinical and follow-up information was collected. The Kaplan-Meier plots with Log
      rank test were used to estimate recurrence-free survival (RFS). Univariate and
      multivariate analysis using the Cox proportional hazard regression model were
      performed to evaluate the impact of any clinicopathological prognostic factors
      (tumor grade, tumor stage, lymph node status, lymphovascular invasion,
      preoperative hydronephrosis, and non-pure urothelial carcinoma) on RFS. RESULTS:
      The 5-year RFS was 84.7% for the entire cohort. Univariate and multivariate
      analysis demonstrated that when using the 2004 WHO classification, lymph node
      status (RR = 4.573, 95% CI: 1.469-14.237), tumor grade (RR = 9.993, 95% CI: 1.325
      75.390) and preoperative hydronephrosis (RR = 3.207, 95% CI: 1.209-8.508)
      presented independent predictors for RFS; while using the 1973 WHO system, lymph
      node status (RR = 9.484, 95% CI: 3.450-26.074) and lymphovascular invasion (RR =
      3.009, 95% CI: 1.062-8.526) were independent predictors. CONCLUSIONS: The 2004
      WHO classification, as an independent factor, is superior to the 1973
      classification for predicting RFS in patients with organ-confined invasive
      bladder cancer treated with radical cystectomy. However, a further perspective
      study is needed to validate its role in prognosis.

PMID- 24091271
TI  - [Application of intraoperative magnetic resonance imaging and multimodal
      navigation in surgical resection of glioblastoma].
AB  - OBJECTIVE: To evaluate the efficacy of intraoperative magnetic resonance imaging
      (iMRI) and multimodal navigation in surgical resection of glioblastoma. METHODS:
      Between February 2009 and July 2010, 76 glioblastoma patients underwent surgical
      resection guided by iMRI and multimodal navigation. The cohort consisted of 43
      male and 33 female patients, with a mean age of 49 years (range: 14-79 years).
      Rates of gross total resection (GTR) and extent of resection (EoR) were
      calculated at first and final iMRI scans.Pearson chi(2) test was used to compare
      the rates of GTR. RESULTS: iMRI and multimodal navigation were successfully
      implemented in all cases. Rates of GTR were misestimated by neurosurgeons in 24
      cases (31.6%), which were confirmed by first iMRI. Total tumor resection were
      achieved in 20 cases (26.3%) as a result of iMRI scan, increasing the rates of
      gross total resection from 52.6% to 78.9% (chi(2) = 11.692, P = 0.001). Extent of
      resection in 28 patients who underwent further tumor resection were increased
      from 81.5% to 98.1%, leading to the overall extent of resection improved from
      92.3% to 98.4%. At 3-month follow-up, 3 cases (3.9%) developed permanent
      neurologic deficits. The mean clinical follow-up was 15.6 months (range 3.0-45.0
      months). The 2-year overall survival rate was 19.7%. The median progression-free
      survival of gross total resection group was 12 months (95% CI: 10.1-13.9 months),
      compared with 9 months (95%CI: 7.9-10.1 months) of the subtotal resection group
      (chi(2) = 4.756, P = 0.029). The overall survival of gross total resection group
      was 16 months (95% CI: 13.7-18.3 months), compared with 12 months (95% CI: 9.7
      14.3 months) of the subtotal resection group (chi(2) = 7.885, P = 0.005).
      CONCLUSION: Combined with multimodal navigation, iMRI helps maximize surgical
      resection of glioblastoma, preserving neurological function while increasing
      progression-free survival and overall survival.

PMID- 24091272
TI  - [Relationship between PUMA and BIM expression in colorectal cancer and tumor
      invasion, metastasis and prognosis].
AB  - OBJECTIVE: To study p53 up-regulated modulator of apoptosis (PUMA) and bcl-2
      interacting mediator of cell death (BIM) of the BH3-only protein family
      expression in colorectal cancer tissues and its relationship with colorectal
      cancer invasion, metastasis and prognosis. METHODS: Immunohistochemical staining
      (EnVision) was used to detect PUMA/BIM expression in 30 cases of normal mucosa,
      30 cases of colorectal adenoma and 142 cases of colorectal cancer tissues.
      RESULTS: PUMA in colorectal cancer tissues was positive expressed (82.4%), which
      was significantly lower than in the normal mucosa colorectal adenomas (96.7%) and
      normal mucosa tissues (96.7%) (both chi(2) = 3.93, P < 0.05). Positive expression
      rate of BIM in colorectal cancer tissues (62.7%) was significantly lower than
      that in colorectal adenomas and normal mucosa (96.7% and 90.0%) (chi(2) = 8.42
      and 13.29, P < 0.01). PUMA and BIM in colorectal cancer tissues were positively
      correlated (r = 0.747, P = 0.000). PUMA expression was related to tumor
      differentiation (chi(2) = 11.87), invasion depth (chi(2) = 11.59), lymph node
      metastasis (chi(2) = 12.82), TNM stage (chi(2) = 33.47) and P-gp expression
      (chi(2) = 18.30), all P < 0.05, but not related to the patients' age, gender,
      tumor size, tumor histological type and GST-pi expression (P > 0.05). BIM
      expression was related to tumor differentiation (chi(2) = 16.19), lymph node
      metastasis (chi(2) = 14.95), TNM stage (chi(2) = 52.66) and P-gp expression
      (chi(2) = 10.60) (P < 0.05), but not related to patients' age, sex, tumor size,
      tumor histological type, invasion depth and GST-pi expression (P > 0.05). 1-, 3-,
      5-year survival rates of the positive expression of PUMA/BIM in patients with
      colorectal cancer were significantly higher than that of PUMA/BIM in patients
      with negative expression (chi(2) = 6.10 and 27.6, P < 0.05). Cox multivariate
      analysis showed that lymph node metastasis (RR = 0.238), TNM stage (RR = 7.895),
      PUMA (RR = 1.691) and BIM (RR = 0.440) could be used as independent prognostic
      indicators (P < 0.05). CONCLUSIONS: PUMA and BIM expressions in colorectal cancer
      are related to the tumor invasion, metastasis and prognosis. Low expressions of
      PUMA and BIM were related to the late period and poor prognosis of colorectal
      cancer patients.

PMID- 24091273
TI  - [Total trans-oral endoscopic thyroidectomy and cervical lymphadenectomy: a human
      cadavers surgery study].
AB  - OBJECTIVE: To find an approach for trans-oral endoscopic thyroidectomy (TOET) and
      cervical lymphadenectomy using conventional endoscopic surgical instruments on
      frozen fresh cadavers. METHODS: Six frozen fresh cadavers were used in three
      groups of trans-oral trocar installation experiments: oral vestibule
      installation, sublingual region installation, and combined bi-vestibular and
      sublingual installation. TOET (with pretrachealis method to thyroid fixation
      removal) and cervical lymphadenectomy were performed experiments on another 6
      frozen fresh cadavers using the best access approach found in the aforementioned
      experiments. RESULTS: In oral vestibule trocar installations, the trocars caused
      large lacerated wound and damaged air tightness. In sublingual installations,
      only one trocar could be installed in the sublingual area because the space in
      sublingual area was limited. In combined bi-vestibular and sublingual
      installations, no gland, vessel or nerve was damaged. Combined bi-vestibular and
      sublingual access were selected as the surgical approach on the basic of analysis
      the merits of each approach. TOET and cervical lymphadenectomy in area III, IV,
      VI, VII were performed without making any accessory damage through combined bi
      vestibular and sublingual access approach. CONCLUSIONS: TOET is feasible.
      Combined bi-vestibular and sublingual approach is available for TOET. Part of the
      cervical lymph nodes could be resected. Pretrachealis approach to thyroid
      fixation removal can still be used.

PMID- 24091274
TI  - Do in-vivo behaviors predict early response in family-based treatment for
      anorexia nervosa?
AB  - The aim of the study is to explore whether identified parental and patient
      behaviors observed in the first few sessions of family-based treatment (FBT)
      predict early response (weight gain of 1.8 kg by session four) to treatment.
      Therapy film recordings from 21 adolescent participants recruited into the FBT
      arm of a multi-site randomized clinical trial were coded for the presence of
      behaviors (length of observed behavior divided by length of session recording) in
      the first, second and fourth sessions. Behaviors that differed between early
      responders and non-early responders on univariate analysis were entered into
      discriminant class analyses. Participants with fewer negative verbal behaviors in
      the first session and were away from table during the meal session less had the
      greatest rates of early response. Parents who made fewer critical statements and
      who did not repeatedly present food during the meal session had children who had
      the greatest rates of early response. In-vivo behaviors in early sessions of FBT
      may predict early response to FBT. Adaptations to address participant resistance
      and to decrease the numbers of critical comments made by parents while
      encouraging their children to eat might improve early response to FBT. 

PMID- 24091275
TI  - Antipathogenic activity of probiotics against Salmonella Typhimurium and
      Clostridium difficile in anaerobic batch culture systems: is it due to synergies
      in probiotic mixtures or the specificity of single strains?
AB  - Probiotics are currently being investigated for prevention of infections caused
      by enteric pathogens. The aim of this in vitro study was to evaluate the
      influence of three single probiotics: Lactobacillus casei NCIMB 30185 (PXN 37),
      Lactobacillus acidophilus NCIMB 30184 (PXN 35), Bifidobacterium breve NCIMB 30180
      (PXN 25) and a probiotic mixture containing the above strains plus twelve other
      strains belonging to the Lactobacillus, Bifidobacterium, Lactococcus,
      Streptococcus and Bacillus genera on the survival of Salmonella Typhimurium and
      Clostridium difficile using pH-controlled anaerobic batch cultures containing
      mixed faecal bacteria. Changes in relevant bacterial groups and effects of
      probiotic addition on survival of the two pathogens were assessed over 24 h.
      Quantitative analysis of bacterial populations revealed that there was a
      significant increase in lactobacilli and/or bifidobacteria numbers, depending on
      probiotic addition, compared with the control (no added probiotic). There was
      also a significant reduction in S. Typhimurium and C. difficile numbers in the
      presence of certain probiotics compared with controls. Of the probiotic
      treatments, two single strains namely L. casei NCIMB 30185 (PXN 37), and B. breve
      NCIMB 30180 (PXN 25) were the most potent in reducing the numbers of S.
      Typhimurium and C. difficile. In addition, the supplementation with probiotics
      into the systems influenced some fermentations parameters. Acetate was found in
      the largest concentrations in all vessels and lactate and formate were generally
      detected in higher amounts in vessels with probiotic addition compared to
      controls.

PMID- 24091276
TI  - Role of the CD137 ligand (CD137L) signaling pathway during Mycobacterium
      tuberculosis infection.
AB  - The role of the CD137-CD137 ligand (CD137L) signaling pathway in T cell co
      stimulation has been well established. Dysregulated CD137 or CD137L stimulation
      can lead to pathological conditions such as inflammatory diseases or cancer.
      However, the contribution of CD137-CD137L interaction to the control of
      infectious diseases has not been extensively studied, with the few available
      reports focusing mainly on viral infections. Here we investigated the role of the
      CD137-CD137L interactions during Mycobacterium tuberculosis infection. Using
      CD137L-deficient mice, we found that absence of the CD137L-mediated signaling
      pathway during M. tuberculosis infection resulted in delayed activation of CD4(+)
      T cells in the draining lymph nodes. This finding was supported by an in vitro
      mixed lymphocyte reaction assay that revealed impaired priming of T cells by
      CD137L-deficient dendritic cells upon mycobacterial infection. In addition,
      greater numbers of CD4(+) T cells and antigen presenting cells were measured in
      the lungs of CD137L-deficient mice. Strikingly, the lung cytokine production
      profile was profoundly altered in M. tuberculosis-infected CD137L-deficient mice
      with lower levels of TNF-alpha, IL-12 and IL-6 and elevated concentrations of IL
      17 compared to their wild type counterparts. However and surprisingly, these
      tangible immunological disorders translated only into a mild and transient
      increase in the bacterial loads and a higher number of granulomatous lesions with
      impaired architecture in the lungs of the CD137L-deficient infected mice.
      Together, while our data support the engagement of the CD137L signaling pathway
      during M. tuberculosis infection, they underscore the functional redundancy and
      robustness of the host defense arsenal deployed against mycobacterial infection. 

PMID- 24091278
TI  - Rural employment scheme is associated with less infant malnutrition, study finds.

PMID- 24091277
TI  - The heterogeneous immune microenvironment in breast cancer is affected by hypoxia
      related genes.
AB  - The immune system constitutes an important first-line defence against malignant
      transformation. However, cancer mediated immunosuppression inactivates the
      mechanisms of host immune surveillance. Cancer cells shut down anti-cancer
      immunity through direct cell-cell interactions with leukocytes and through
      soluble factors, establishing an immunosuppressive environment for unimpeded
      cancer growth. The composition of the immunosuppressive microenvironment in
      breast tumours is not well documented. To address this question, selected
      immunosuppressive factors were analyzed in tumour specimens from 33 breast cancer
      patients after surgery. The mRNA expression of selected genes was quantified in
      fresh tumour samples. Tumour infiltrating leukocytes were characterized by flow
      cytometry to identify regulatory T cells, myeloid derived suppressor cells, and
      type 2 macrophages. Statistical analysis revealed several interesting
      correlations between the studied parameters and clinical features. Overall, a
      surprisingly high degree of heterogeneity in the composition of the
      immunosuppressive environment was found across all breast cancer samples which
      adds to the complexity of this disease. The influence of the hypoxia inducible
      factors (HIFs) on the immune microenvironment was also addressed. The level of
      HIFs correlated with hormone receptor status and the expression of several
      immunosuppressive molecules. Targeting HIFs might not only sensitize breast
      tumours for radiation and chemotherapies but also interfere with cancer
      immunosuppression. 

PMID- 24091279
TI  - GPs face a L400m "black hole" as a result of cuts over the past three years.

PMID- 24091280
TI  - Intensive comprehensive aphasia programs: an international survey of practice.
AB  - BACKGROUND: In response to the need to simultaneously address multiple domains of
      the International Classification of Functioning, Disability and Health (ICF) in
      aphasia therapy and to incorporate intensive treatment doses consistent with
      principles of neuroplasticity, a potentially potent treatment option termed
      intensive comprehensive aphasia programs (ICAPs) has been developed. OBJECTIVE:
      To conduct an international survey of ICAPs to determine the extent of their use
      and to explore current ICAP practices. METHODS: A 32-item online survey was
      distributed internationally through Survey Monkey between May and August 2012.
      The survey addressed ICAP staffing, philosophy, values, funding, admission
      criteria, activities, family involvement, outcome measures, and factors
      considered important to success. RESULTS: Twelve ICAPs responded: 8 from the
      United States, 2 from Canada, and 1 each from Australia and the United Kingdom.
      The majority of ICAPs are affiliated with university programs and are funded
      through participant self-pay. ICAPs emphasize individualized treatment goals and
      evidence-based practices, with a focus on applying the principles of
      neuroplasticity related to repetition and intensity of treatment. On average, 6
      people with aphasia attend each ICAP, for 4 days per week for 4 weeks, receiving
      about 100 hours of individual, group, and computer-based treatment. Speech
      language pathologists, students, and volunteers staff the majority of ICAPs.
      CONCLUSIONS: ICAPs are increasing in number but remain a rare service delivery
      option. They address the needs of individuals who want access to intensive
      treatment and are interested in making significant changes to their communication
      skills and psychosocial well-being in a short period of time. Their efficacy and
      cost-effectiveness require future investigation.

PMID- 24091281
TI  - Retrospective analysis of outcomes from two intensive comprehensive aphasia
      programs.
AB  - Positive outcomes from intensive therapy for individuals with aphasia have been
      reported in the literature. Little is known about the characteristics of
      individuals who attend intensive comprehensive aphasia programs (ICAPs) and what
      factors may predict who makes clinically significant changes when attending such
      programs. Demographic data on participants from 6 ICAPs showed that individuals
      who attend these programs spanned the entire age range (from adolescence to late
      adulthood), but they generally tended to be middle-aged and predominantly male.
      Analysis of outcome data from 2 of these ICAPs found that age and gender were not
      significant predictors of improved outcome on measures of language ability or
      functional communication. However, time post onset was related to clinical
      improvement in functional communication as measured by the Communication
      Activities of Daily Living, second edition (CADL-2). In addition, for one sample,
      initial severity of aphasia was related to outcome on the Western Aphasia Battery
      Revised, such that individuals with more severe aphasia tended to show greater
      recovery compared to those with mild aphasia. Initial severity of aphasia also
      was highly correlated with changes in CADL-2 scores. These results suggest that
      adults of all ages with aphasia in either the acute or chronic phase of recovery
      can continue to show positive improvements in language ability and functional
      communication with intensive treatment. 

PMID- 24091282
TI  - Clinician perspectives of an intensive comprehensive aphasia program.
AB  - BACKGROUND: Intensive comprehensive aphasia programs (ICAPs) have increased in
      number in recent years in the United States and abroad. OBJECTIVE: To describe
      the experiences of clinicians working in an ICAP. METHODS: A phenomenological
      approach was taken. Seven clinicians from 3 ICAPs were interviewed in person or
      on the phone. Their interviews were transcribed and coded for themes relating to
      their experiences. RESULTS: Clinicians described 3 major themes. The first theme
      related to the intensity component of the ICAP that allowed clinicians to provide
      in-depth treatment and gave them a different perspective with regard to providing
      treatment and the potential impact on the person with aphasia. The second theme
      of rewards for the clinicians included learning and support, seeing progress, and
      developing relationships with their clients and family members. Third, challenges
      were noted, including the time involved in learning new therapy techniques,
      patient characteristics such as chronicity of the aphasia, and the difficulty of
      returning to work in typical clinical settings after having experienced an ICAP.
      CONCLUSIONS: Although there is a potential for bias with the small sample size,
      this pilot study gives insight into the clinician perspective of what makes
      working in an ICAP both worthwhile and challenging.

PMID- 24091283
TI  - Setting a research agenda to inform intensive comprehensive aphasia programs.
AB  - Research into intensive comprehensive aphasia programs (ICAPs) has yet to show
      that this service delivery model is efficacious, effective, has cost utility, or
      can be broadly implemented. This article describes a phased research approach to
      the study of ICAPs and sets out a research agenda that considers not only the
      specific issues surrounding ICAPs, but also the phase of the research. Current
      ICAP research is in the early phases, with dosing and outcome measurement as
      prime considerations as well as refinement of the best treatment protocol. Later
      phases of ICAP research are outlined, and the need for larger scale collaborative
      funded research is recognized. The need for more rapid translation into practice
      is also acknowledged, and the use of hybrid models of phased research is
      encouraged within the ICAP research agenda. 

PMID- 24091284
TI  - Personality differences among patients with chronic aphasia predict improvement
      in speech-language therapy.
AB  - BACKGROUND: Negative affectivity and neurocognitive deficits including executive
      dysfunction have been shown to be detrimental to rehabilitation therapies.
      However, research on the relationship between neuropsychological deficits and
      improvement in speech-language therapy (SLT) for aphasia is sparse. OBJECTIVE: To
      examine the relationships among neurocognitive and psychological functioning and
      improvement in SLT following aphasia due to stroke. METHODS: Fifty patients who
      were >= 9 months post stroke and enrolled in outpatient SLT to treat aphasia
      participated. Using standard language assessment measures, the authors evaluated
      language functioning at initiation of the study and after participants completed
      various SLT protocols. Executive functioning, visuospatial skills, attention, and
      memory also were assessed to provide indices of convergent and discriminant
      validity. Participants' mood and affectivity were evaluated by self-report, and
      their functional abilities and recovery of function since stroke were assessed
      via caregiver report. RESULTS: A multiple regression model testing the combined
      powers of neurocognitive and psychological variables was significant (P = .004,
      R2 = 0.33), with psychological and neurocognitive functioning accounting for 15%
      of the variance in relative language change beyond that accounted for by stroke
      severity and gross cognitive functioning. Negative affectivity expressed on the
      Positive and Negative Affectivity Scale made unique contributions to the model.
      CONCLUSIONS: Improvement in SLT is substantially related to neurocognitive and
      psychological functioning, particularly affectivity. Assessment of these
      characteristics may assist in identifying patients who are likely to improve and
      in tailoring treatment programs to yield optimal outcomes.

PMID- 24091285
TI  - Standardizing the approach to evidence-based upper limb rehabilitation after
      stroke.
AB  - BACKGROUND AND PURPOSE: To describe the development of a clinical algorithm to
      enable standardized intervention prescription and progression for upper limb
      rehabilitation post stroke. METHODS: We developed a standardized clinical
      algorithm that involved assessment of 18 critical impairments of upper limb
      function and application of task-specific exercises appropriate to the level of
      impairment. These tasks were consistent with recent evidence-based guidelines. We
      tested the feasibility of the algorithm with 20 participants recently discharged
      from inpatient rehabilitation following stroke who received outpatient therapy
      according to the clinical algorithm. Participants' abilities were regularly re
      evaluated and task difficulty progressed. Outcomes were assessed at the level of
      impairment (Action Research Arm Test, Fugl-Meyer Assessment) and activity (Motor
      Activity Log). RESULTS: All participants attended the 9 sessions of training over
      the 3-week intervention period (100% compliance). No adverse events were
      reported. There were significant improvements in all outcome measures (P < .01).
      CONCLUSIONS: This evidence-based upper limb clinical algorithm provides a
      framework for standardizing task-specific training following stroke based on the
      assessment of functioning of the individual following stroke in day-to-day life.
      This approach is appropriate for patients with different functional levels and
      may be used to standardize individual or group self-directed practice sessions or
      to standardize the intervention and progressions in experimental studies.

PMID- 24091286
TI  - Sensory impairments of the lower limb after stroke: a pooled analysis of
      individual patient data.
AB  - OBJECTIVE: To obtain more generalizable information on the frequency and factors
      influencing sensory impairment after stroke and their relationship to mobility
      and function. METHOD: A pooled analysis of individual data of stroke survivors (N
      = 459); mean (SD) age = 67.2 (14.8) years, 54% male, mean (SD) time since stroke
      = 22.33 (63.1) days, 50% left-sided weakness. Where different measurement tools
      were used, data were recorded. Descriptive statistics described frequency of
      sensory impairments, kappa coefficients investigated relationships between
      sensory modalities, binary logistic regression explored the factors influencing
      sensory impairments, and linear regression assessed the impact of sensory
      impairments on activity limitations. RESULTS: Most patients' sensation was intact
      (55%), and individual sensory modalities were highly associated (kappa = 0.60, P
      < .001). Weakness and neglect influenced sensory impairment (P < .001), but
      demographics, stroke pathology, and spasticity did not. Sensation influenced
      independence in activities of daily living, mobility, and balance but less
      strongly than weakness. CONCLUSIONS: Pooled individual data analysis showed
      sensation of the lower limb is grossly preserved in most stroke survivors but,
      when present, it affects function. Sensory modalities are highly interrelated;
      interventions that treat the motor system during functional tasks may be as
      effective at treating the sensory system as sensory retraining alone.

PMID- 24091288
TI  - Postantibiotic effect of disinfection treatment by photolysis of hydrogen
      peroxide.
AB  - The purpose of the present study was to evaluate the postantibiotic effect (PAE)
      of the disinfection treatment by photolysis of H2O2. Postantibiotic effect was
      induced in Staphylococcus aureus and Streptococcus salivarius by exposing the
      bacteria to H2O2 at concentrations of 250-1000 mmol/l, laser irradiation at a
      wavelength of 405 nm, and the combination of both (photolysis of H2O2) for 10-30
      seconds. The photolysis of H2O2 induced significantly longer PAE than other
      treatments. The PAE was augmented dependently on not only the concentration of
      H2O2 but the laser irradiation time. Electron spin resonance analysis showed that
      the hydroxyl radical was also generated dependently on both the concentration of
      H2O2 and the laser irradiation time, suggesting that the hydroxyl radicals
      contribute to the PAE. These results suggest that the disinfection treatment by
      photolysis of H2O2 induces PAE in S. aureus and S. salivarius even though they
      were treated for only 10-30 seconds. 

PMID- 24091287
TI  - Case study: application of isometric progressive resistance oropharyngeal therapy
      using the Madison Oral Strengthening Therapeutic device.
AB  - PURPOSE: Isometric progressive resistance oropharyngeal (I-PRO) therapy improves
      swallowing function; however, current devices utilize a single sensor that
      provides limited information or are prohibitively expensive. This single-subject
      study presents results of I-PRO therapy, detraining, and maintenance using the 5
      sensor Madison Oral Strengthening Therapeutic (MOST) device combined with upper
      esophageal sphincter (UES) dilatation. METHODS: A 56-year-old female nurse who
      was 27 months post stroke and subsequent to traditional behavioral interventions
      and UES dilatations presented limited to gastrostomy tube intake only and
      expectorating all saliva. She completed 8 weeks of I-PRO therapy, 5 weeks of
      detraining, and 9 weeks of I-PRO maintenance (reduced frequency) followed by a
      third UES dilatation post intervention. Data included diet inventory, lingual
      pressures (MOST), lingual volume (magnetic resonance imaging), postswallow
      residue (videofluoroscopy), UES and pharyngeal pressures (high-resolution
      manometry), and quality of life (QOL). RESULTS: Findings after 8 weeks of I-PRO
      therapy were progression to general oral diet, 15 lb weight gain, increased
      isometric pressures (Delta ?16 kPa) with transference to swallowing pressures,
      increased lingual volume (8.3%), reduced pharyngeal wall residue (P = .03),
      increased pharyngeal pressures (Delta ? 43 mm Hg) and increased UES opening
      (nadir) pressures (Delta ? 9 mm Hg) with improved temporopressure coordination
      across the pharynx, and improved QOL. After detraining, decreased isometric
      pressures and reduced UES opening were noted. After I-PRO maintenance, isometric
      anterior lingual pressures returned to levels noted after the 8 weeks of
      intervention. CONCLUSION: I-PRO therapy, facilitated by the MOST device combined
      with instrumental UES dilatation, improved swallow safety, increased
      oropharyngeal intake, and facilitated UES opening while enriching QOL.

PMID- 24091289
TI  - From crossbreeding to biotechnology-facilitated improvement of banana and
      plantain.
AB  - The annual harvest of banana and plantain (Musa spp.) is approximately 145
      million tons worldwide. About 85% of this global production comes from small
      plots and kitchen or backyard gardens from the developing world, and only 15%
      goes to the export trade. Musa acuminata and Musa balbisiana are the ancestors of
      several hundreds of parthenocarpic Musa diploid and polyploid cultivars, which
      show multiple origins through inter- and intra-specific hybridizations from these
      two wild diploid species. Generating hybrids combining host plant resistance to
      pathogens and pests, short growth cycles and height, high fruit yield,
      parthenocarpy, and desired quality from the cultivars remains a challenge for
      Musa crossbreeding, which started about one century ago in Trinidad. The success
      of Musa crossbreeding depends on the production of true hybrid seeds in a crop
      known for its high levels of female sterility, particularly among polyploid
      cultivars. All banana export cultivars grown today are, however, selections from
      somatic mutants of the group Cavendish and have a very narrow genetic base, while
      smallholders in sub-Saharan Africa, tropical Asia and Latin America use some bred
      hybrids (mostly cooking types). Musa improvement goals need to shift to address
      emerging threats because of the changing climate. Innovative cell and molecular
      biology tools have the potential to enhance the pace and efficiency of genetic
      improvement in Musa. Micro-propagation has been successful for high throughput of
      clean planting materials while in vitro seed germination assists in obtaining
      seedlings after inter-specific and across ploidy hybridization. Flow cytometry
      protocols are used for checking ploidy among genebank accessions and breeding
      materials. DNA markers, the genetic maps based on them, and the recent sequencing
      of the banana genome offer means for gaining more insights in the genetics of the
      crops and to identifying genes that could lead to accelerating Musa betterment.
      Likewise, DNA fingerprinting has been useful to characterize Musa diversity.
      Genetic engineering provides a complementary tool to Musa breeders who can
      introduce today transgenes that may confer resistance to bacteria, fungi and
      nematodes, or enhance pro-vitamin A fruit content. In spite of recent advances,
      the genetic improvement of Musa depends on a few crossbreeding programs (based in
      Brazil, Cameroon, Cote d'Ivoire, Guadeloupe, Honduras, India, Nigeria, Tanzania
      and Uganda) or a handful of genetic engineering endeavors (Australia, Belgium,
      India, Kenya, Malaysia and Uganda). Development investors (namely international
      aid and philanthropy) should therefore increase their funding to genetically
      enhance this crop that ranks among the 10-top staple foods of the developing
      world.

PMID- 24091290
TI  - Can a late bloomer become an early bird? Tools for flowering time adjustment.
AB  - The transition from the vegetative to reproductive stage followed by
      inflorescence is a critical step in plant life; therefore, studies of the genes
      that influence flowering time have always been of great interest to scientists.
      Flowering is a process controlled by many genes interacting mutually in a genetic
      network, and several hypothesis and models of flowering have been suggested so
      far. Plants in temperate climatic conditions must respond mainly to changes in
      the day length (photoperiod) and unfavourable winter temperatures. To avoid
      flowering before winter, some plants exploit a specific mechanism called
      vernalization. This review summarises current achievements in the study of genes
      controlling flowering in the dicot model species thale cress (Arabidopsis
      thaliana), as well as in monocot model species rice (Oryza sativa) and temperate
      cereals such as barley (Hordeum vulgare L.) and wheat (Triticum aestivum L.). The
      control of flowering in crops is an attractive target for modern plant breeding
      efforts aiming to prepare locally well-adapted cultivars. The recent progress in
      genomics revealed the importance of minor-effect genes (QTLs) and natural allelic
      variation of genes for fine-tuning flowering and better cultivar adaptation. We
      briefly describe the up-to-date technologies and approaches that scientists may
      employ and we also indicate how these modern biotechnological tools and "-omics"
      can expand our knowledge of flowering in agronomically important crops. 

PMID- 24091291
TI  - The role of ABA and MAPK signaling pathways in plant abiotic stress responses.
AB  - As sessile organisms, plants have developed specific mechanisms that allow them
      to rapidly perceive and respond to stresses in the environment. Among the
      evolutionarily conserved pathways, the ABA (abscisic acid) signaling pathway has
      been identified as a central regulator of abiotic stress response in plants,
      triggering major changes in gene expression and adaptive physiological responses.
      ABA induces protein kinases of the SnRK family to mediate a number of its
      responses. Recently, MAPK (mitogen activated protein kinase) cascades have also
      been shown to be implicated in ABA signaling. Therefore, besides discussing the
      role of ABA in abiotic stress signaling, we will also summarize the evidence for
      a role of MAPKs in the context of abiotic stress and ABA signaling. 

PMID- 24091292
TI  - Pharmacological efficacy of anti-IL-1beta scFv, Fab and full-length antibodies in
      treatment of rheumatoid arthritis.
AB  - Rheumatoid arthritis (RA) is a chronic autoimmune inflammatory disease that
      mainly causes the synovial joint inflammation and cartilage destruction.
      Interleukin-1beta (IL-1beta) is an important proinflammatory cytokine involved in
      the pathogenesis of RA. In this study, we constructed and expressed anti-IL-1beta
      full-length antibody in CHO-K1-SV, anti-IL-1beta-Fab and anti-IL-1beta-scFv in
      Rosetta. We compared the therapeutic efficacy of three anti-IL-1beta antibodies
      for CIA mice. Mice with CIA were subcutaneously injected with humanized anti-IL
      1beta-scFv, anti-IL-1beta-Fab or anti-IL-1beta-full-length antibody. The effects
      of treatment were determined by arthritis severity score, autoreactive humoral,
      cellular immune responses, histological lesion and cytokines production. Compared
      with anti-IL-1beta-scFv treatments, anti-IL-1beta-Fab and anti-IL-1beta-full
      length antibody therapy resulted in more significant effect in alleviating the
      severity of arthritis by preventing bone damage and cartilage destruction,
      reducing humoral and cellular immune responses, and down-regulating the
      expression of IL-1beta, IL-6, IL-2, IFN-gamma, TNF-alpha and MMP-3 in
      inflammatory tissue. The therapeutic effects of anti-IL-1beta-Fab and anti-IL
      1beta-full-length antibodies on CIA mice had no significant difference. However,
      production of anti-IL-1beta-full-length antibody in eukaryotic system is, in
      general, time-consuming and more expensive than that of anti-IL-1beta-Fab in
      prokaryotic systems. In conclusion, as a small molecule antibody, anti-IL-1beta
      Fab is an ideal candidate for RA therapy.

PMID- 24091293
TI  - Engineering of a recombinant trivalent single-chain variable fragment antibody
      directed against rabies virus glycoprotein G with improved neutralizing potency.
AB  - Human and equine rabies immunoglobulins are currently available for passive
      immunization against rabies. However, these are hampered by the limited supply
      and some drawbacks. Advances in antibody engineering have led to overcome issues
      of clinical applications and to improve the protective efficacy. In the present
      study, we report the generation of a trivalent single-chain Fv (scFv50AD1-Fd),
      that recognizes the rabies virus glycoprotein, genetically fused to the
      trimerization domain of the bacteriophage T4 fibritin, termed 'foldon' (Fd).
      scFv50AD1-Fd was expressed as soluble recombinant protein in bacterial
      periplasmic space and purified through affinity chromatography. The molecular
      integrity and stability were analyzed by polyacrylamide gradient-gel
      electrophoresis, size-exclusion chromatography and incubation in human sera. The
      antigen-binding properties of the trimeric scFv were analyzed by direct and
      competitive-ELISA. Its apparent affinity constant was estimated at 1.4 +/- 0.25 *
      10(9)M(-1) and was 75-fold higher than its monovalent scFv (1.9 +/- 0.68 *
      10(7)M(-1)). The scFv50AD1-Fd neutralized rabies virus in a standard in vitro and
      in vivo neutralization assay. We showed a high neutralization activity up to 75
      fold compared with monovalent format and the WHO standard serum. The gain in
      avidity resulting from multivalency along with an improved biological activity
      makes the trivalent scFv50AD1-Fd construct an important reagent for rabies
      protection. The antibody engineering approach presented here may serve as a
      strategy for designing a new generation of anti-rabies for passive immunotherapy.

PMID- 24091294
TI  - Human cathelicidin LL-37-derived peptide IG-19 confers protection in a murine
      model of collagen-induced arthritis.
AB  - Current therapies for autoimmune chronic inflammatory diseases e.g. rheumatoid
      arthritis (RA) include inhibitors of inflammatory cytokines. However, these
      therapies can result in increased risk of infections. There is a need to explore
      alternate strategies that can control inflammation without compromising the
      innate ability to resolve infections. In this study, we examined the effect of
      small peptides derived from endogenous cathelicidin peptides in a murine model of
      collagen-induced arthritis (CIA). Cathelicidins are immunomodulatory peptides
      known to control infections. We demonstrate that the administration of the
      peptide IG-19, which represents an internal segment of the human cathelicidin LL
      37, decreased disease severity and significantly reduced the serum levels of
      antibodies against collagen type II in the CIA model. IG-19 peptide reduced
      cellular infiltration in joints, prevented cartilage degradation and suppressed
      pro-inflammatory cytokines in the CIA mice. We also showed that not all
      cathelicidin-derived peptides exhibit similar functions. A bovine cathelicidin
      derived peptide IDR-1018 did not exhibit the beneficial effects observed with the
      human cathelicidin LL-37-derived peptide IG-19, in the same murine model of CIA.
      This is the first study to provide evidence demonstrating the ability of a
      peptide derived from the human cathelicidin LL-37 to alleviate the arthritic
      disease process in a murine model of RA. Our results has lead us to propose a new
      approach for controlling autoimmune chronic inflammatory disorders such as RA, by
      using specific synthetic derivatives of endogenous host defence peptides.
      Cathelicidin-derived peptides are particularly attractive for their dual
      antimicrobial and anti-inflammatory actions.

PMID- 24091295
TI  - In silico analyses of structural and allergenicity features of sapodilla
      (Manilkara zapota) acidic thaumatin-like protein in comparison with allergenic
      plant TLPs.
AB  - Thaumatin-like proteins (TLPs) belong to the pathogenesis-related family (PR-5)
      of plant defense proteins. TLPs from only 32 plant genera have been identified as
      pollen or food allergens. IgE epitopes on allergens play a central role in food
      allergy by initiating cross-linking of specific IgE on basophils/mast cells. A
      comparative analysis of pollen- and food-allergenic TLPs is lacking. The main
      objective of this investigation was to study the structural and allergenicity
      features of sapodilla (Manilkara zapota) acidic TLP (TLP 1) by in silico methods.
      The allergenicity prediction of composite sequence of sapodilla TLP 1 (NCBI
      B3EWX8.1, G5DC91.1) was performed using FARRP, Allermatch and Evaller web tools.
      A homology model of the protein was generated using banana TLP template (1Z3Q) by
      HHPRED-MODELLER. B-cell linear epitope prediction was performed using BCpreds and
      BepiPred. Sapodilla TLP 1 matched significantly with allergenic TLPs from olive,
      kiwi, bell pepper and banana. IgE epitope prediction as performed using AlgPred
      indicated the presence of 2 epitopes (epitope 1: residues 36-48; epitope 2:
      residues 51-63), and a comprehensive analysis of all allergenic TLPs displayed up
      to 3 additional epitopes on other TLPs. It can be inferred from these analyses
      that plant allergenic TLPs generally carry 2-3 IgE epitopes. ClustalX alignments
      of allergenic TLPs indicate that IgE epitopes 1 and 2 are common in food
      allergenic TLPs, and IgE epitopes 2 and 3 are common in pollen allergenic TLPs;
      IgE epitope 2 overlaps with a portion of the thaumatin family signature. The
      secondary structural elements of TLPs vary markedly in regions 1 and 2 which
      harbor all the predicted IgE epitopes in all food and pollen TLPs in either of
      the region. Further, based on the number of IgE epitopes, food TLPs are grouped
      into rosid and non-rosid clades. The number and distribution of the predicted IgE
      epitopes among the allergenic TLPs may explain the specificity of food or pollen
      allergy as well as the varied degree of cross-reactivity among plant foods and/or
      pollens.

PMID- 24091296
TI  - Antigenic epitopes of MAP2694 homologous to T-cell receptor gamma-chain are
      highly recognized in multiple sclerosis Sardinian patients.
AB  - Mycobacterium avium ss. paratuberculosis (MAP) is an intracellular pathogen
      recently associated with multiple sclerosis (MS). Aiming to identify
      immunodominant epitopes belonging to MS related protein MAP2694 (UniProt
      accession no. Q73WG6), we investigated the binding activity of selected peptides
      against MS Sardinian sera. An overlapping 9-mers peptide library was synthesized
      spanning the entire aminoacidic sequence of the protein. Peripheral blood was
      collected from 47 MS patients and 42 sex and age matched healthy volunteers and
      subjected to enzyme-linked immunosorbent assay (ELISA) in order to investigate
      the reaction against the linear peptides generated. Two out of 58 synthetic 9
      mers were strongly recognized by MS patients' antibodies compared to controls. A
      competitive inhibition assay demonstrated that these two epitopes are
      immunodominant antibody targets within MAP2694 protein, as sera pre-adsorbed with
      these peptides were able to significantly block the antibody reaction to the
      MAP2694 protein, even if at a lesser extent than MAP2694 protein itself.

PMID- 24091297
TI  - The role of Cepsilon2, Cepsilon3, and Cepsilon4 domains in human and canine IgE
      and their contribution to FcepsilonRIalpha interaction.
AB  - The Cepsilon2 and Cepsilon4 domains are considered as scaffolds, allowing
      Cepsilon3 domains to assume an appropriate orientation to interact with
      FcepsilonRI (Wurzburg and Jardetzky, 2002; Hunter et al., 2008). Human/canine IgE
      chimeric antibodies were expressed to assess the nature of the contribution of
      Cepsilon2 and Cepsilon4 domains to bind to and induce target cell degranulation
      via FcepsilonRIalpha. Our results indicate that for (1) Cepsilon3 domains in IgE
      of canine and human origin are the only necessary region for binding to
      FcepsilonRIalpha. (2) The interaction of canine IgE with human sFcepsilonRIalpha
      is significantly enhanced by contributions from both Cepsilon2 and Cepsilon4
      domains of dog origin. (3) The canine/human IgE chimeric antibody construct
      rapidly dissociates from its the receptor when the canine Cepsilon2 and Cepsilon4
      domains are replaced by the homologous human Fc domains which do not confer a
      conformation on the Cepsilon3 domain to facilitate stable interaction with canine
      FcRIalpha. Kinetic constants for the binding of this chimera to the soluble
      extracellular domain of the receptor indicate an approximate 120-fold decrease in
      the affinity for canine sFcepsilonRIalpha (ka=5.30 * 10(2)M(-1)s(-1)) and a 330
      fold increase in the dissociation from canine sFcepsilonRIalpha (KD=6.9 * 10(
      6)M(-1)), compared to the wild type IgE kinetic constants (Ka=6.30 * 10(4)M(-1)s(
      1); KD=2.1 * 10(-8)M(-1)). Although canine IgE does engage human
      FcepsilonRIalpha, canine Cepsilon2 and Cepsilon4 do not contribute to the high
      affinity of interaction with human FcepsilonRIalpha. Upon replacement of human
      Cepsilon2 and Cepsilon4 domain by the canine homologues, human IgE Cepsilon3 only
      retains a low affinity for the human receptor, which shows that Cepsilon2 and
      Cepsilon4 domains in human IgE Fc contribute significantly to the interaction
      with its cognate receptor.

PMID- 24091298
TI  - The relationship between impact force, neck strength, and neurocognitive
      performance in soccer heading in adolescent females.
AB  - Head impacts are common in contact sports, but only recently has there been a
      rising awareness of the effects of subconcussive impacts in adolescent athletes.
      A better understanding of how to attenuate head impacts is needed and therefore,
      this study investigated the relationship between neck strength, impact, and
      neurocognitive function in an acute bout of soccer heading in a sample of female
      high school varsity soccer players. Seventeen participants completed the ImPACT
      neurocognitive test and had their isometric neck strength tested (flexion,
      extension, and bilateral flexion) before heading drills. Each participant was
      outfitted with custom headgear with timing switches and a three-dimensional
      accelerometer affixed to the back of the head, which allowed for measurement of
      impact during heading. Participants performed a series of 15 directional headers,
      including 5 forward, 5 left and 5 right headers in a random order, then completed
      the ImPACT test again. Neurocognitive tests revealed no significant changes
      following heading. However, there were statistically significant, moderate,
      negative correlations (r = -0.500:-0.757, p < .05) between neck strength and
      resultant header acceleration, indicating that those with weaker necks sustained
      greater impacts. This suggests neck strengthening may be an important component
      of any head injury prevention/reduction program. 

PMID- 24091299
TI  - Purification of high value proteins from particle containing potato fruit juice
      via direct capture membrane adsorption chromatography.
AB  - Potato fruit juice (PFJ) is a by-product from industrial starch production. It
      still contains several valuable components such as amino acids, minerals and
      proteins. An economic technology for the isolation and purification of different
      native potato proteins is the ion exchange chromatography, which can be performed
      either by classical bed chromatography or by membrane adsorption chromatography
      (MA-IEX). An already published MA-IEX process for the downstreaming of PFJ is
      based on the following steps: prefiltration/microfiltration, fractionation with
      MA-IEX, ultra-/diafiltration and finally drying. In order to further minimize
      process complexity and costs, new MA-IEX-modules were designed and tested in this
      research project to facilitate the processing of crude, particle-containing
      solutions using a tangential flow through the membranes. Modules with fleece
      polymer spacers and extruded polymer spacers, as well as different spacer channel
      sizes were tested for their binding capacities and their long-term stability. An
      optimized setup was found for the technical scale. Modules with extruded polymer
      spacers channel size 250 MUm show the highest binding capacities (anion exchanger
      approx. 0.34 mg/cm(2), cation exchanger approx. 0.16 mg/cm(2)), while the modules
      with extruded polymer spacers channel size 480 MUm show the best long-term
      stability with 23 passes without intermediary cleaning.

PMID- 24091301
TI  - The effect of public awareness campaigns on suicides: evidence from Nagoya,
      Japan.
AB  - BACKGROUND: Public awareness campaigns about depression and suicide have been
      viewed as highly effective strategies in preventing suicide, yet their
      effectiveness has not been established in previous studies. This study evaluates
      the effectiveness of a public-awareness campaign by comparing suicide counts
      before and after a city-wide campaign in Nagoya, Japan, where the city government
      distributed promotional materials that were aimed to stimulate public awareness
      of depression and promote care-seeking behavior during the period of 2010-2012.
      METHODS: In each of the sixteen wards of the city of Nagoya, we count the number
      of times that the promotional materials were distributed per month and then
      examine the association between the suicide counts and the frequency of
      distributions in the months following such distributions. We run a Poisson
      regression model that controls for the effects of ward-specific observed and
      unobserved heterogeneities and temporal shocks. FINDINGS: Our analysis indicates
      that more frequent distribution of the campaign material is associated with a
      decrease in the number of suicides in the subsequent months. The campaign was
      estimated to have been especially effective for the male residents of the city.
      LIMITATION: The underlying mechanism of how the campaign reduced suicides remains
      to be unclear. CONCLUSION: Public awareness campaigns can be an effective
      strategy in preventing suicide.

PMID- 24091300
TI  - Engineering a repression-free catabolite-enhanced expression system for a
      thermophilic alpha-amylase from Bacillus licheniformis MSG.
AB  - Most expression systems used for the over production of many enzymes employ
      carbon catabolite repressible promoters and hence must use sugar free, rich
      complex media. Use of expression systems to overcome carbon repression opens an
      avenue for exploiting cheap carbon sources for the production of recombinant
      enzymes. A self-inducible, catabolite repression free and above all a glucose
      activated expression system has been developed using an industrially suitable
      thermophilic alpha-amylase as a model. The alpha-amylase gene of Bacillus
      licheniformis MSG without the 5' cre operator produced unimpeded glucose-enhanced
      expression when fused to the phosphate starvation-inducible strong pst promoter
      with optimum translation signals in a protease deficient Bacillus subtilis. A
      combination of high glucose with limited phosphate permitted sufficient biomass
      and fast transition to quiescent phase by phosphate starvation permitting 1250
      fold induction for 70 h. A ~300-fold high productivity (9070 U mL(-1)) and 131
      fold increase in specific expression in 2% glucose and a 100-fold high yield in
      4% molasses were obtained compared to the production by the parent strain. The
      yield was 18.5-fold higher than that from the native promoter in an isogenic
      clone. This strategy of catabolite enhanced enzyme expression uncoupled from
      biomass formation can be applied for cost effective high production of proteins
      using starch or molasses.

PMID- 24091302
TI  - Psychiatric disorders in patients presenting to hospital following self-harm: a
      systematic review.
AB  - BACKGROUND: Psychiatric disorders occur in approximately 90% of individuals dying
      by suicide. The prevalence of psychiatric disorders in people who engage in non
      fatal self-harm has received less attention. METHOD: Systematic review using
      electronic databases (Embase, PsychINFO and Medline) for English language
      publications of studies in which psychiatric disorders have been assessed using
      research or clinical diagnostic schedules in self-harm patients of all ages
      presenting to general hospitals, followed by meta-analyses using random effects
      methods. RESULTS: A total of 50 studies from 24 countries were identified.
      Psychiatric (Axis I) disorders were identified in 83.9% (95% CI 74.7-91.3%) of
      adults and 81.2% (95% CI 60.9-95.5%) of adolescents and young persons. The most
      frequent disorders were depression, anxiety and alcohol misuse, and additionally
      attention deficit hyperactivity disorder (ADHD) and conduct disorder in younger
      patients. Personality (Axis II) disorders were found in 27.5% (95% CI 17.6-38.7%)
      of adult patients. Psychiatric disorders were somewhat more common in patients in
      Western (89.6%, 95% CI 83.0-94.7%) than non-Western countries (70.6%, 95% CI 50.1
      87.6%). LIMITATIONS: Heterogeneity between study results was generally high.
      There were differences between studies in identification of study participants
      and diagnostic procedures. CONCLUSIONS: Most self-harm patients have psychiatric
      disorders, as found in people dying by suicide. Depression and anxiety disorders
      are particularly common, together with ADHD and conduct disorder in adolescents.
      Psychosocial assessment and aftercare of self-harm patients should include
      careful screening for such disorders and appropriate therapeutic interventions.
      Longitudinal studies of the progress of these disorders are required.

PMID- 24091303
TI  - Anxiety sensitivity and impairment: evidence for a direct association and partial
      mediation by subclinical anxiety symptoms.
AB  - BACKGROUND: Mounting evidence suggests that specific psychological risk factors
      increase the likelihood for the development of anxiety psychopathology. Anxiety
      sensitivity (AS), the fear of the consequences of anxiety, is one such risk
      factor. However, very little is known about the consequences of having elevated
      AS prior to the development of diagnosable psychopathology. We hypothesized that
      elevated AS may create impairment among premorbid individuals. The aims of the
      present study were twofold. The first aim was to examine whether having elevated
      AS would be predictive of impairment in a nonclinical sample. The second aim was
      to examine whether subclinical anxiety symptoms would partially mediate the
      association between AS and impairment in daily life. METHOD: These aims were
      examined in two studies utilizing samples of individuals with elevated levels of
      AS. Study 1 (N=387) and Study 2 (N=79) were comprised of participants with
      elevated AS. Participants completed a battery of questionnaires and a diagnostic
      interview to assess for risk status. Only participants without an anxiety
      disorder were eligible to participate in the study to ensure that they were in
      the premorbid stage. RESULTS: In Study 1, there was a direct effect of AS on
      impairment. Additionally, there was evidence for anxiety symptoms acting as a
      partial mediator in the relation between AS and impairment. Study 2 revealed the
      same pattern of results, with AS having a significant direct effect on impairment
      that was partially mediated by anxiety symptoms. LIMITATIONS: The samples
      utilized in the present sample were primarily Caucasian females, thereby
      potentially limiting the generalizability of these findings. CONCLUSIONS: This
      study provides evidence that a premorbid risk factor is associated with
      impairment before the actual development of an anxiety disorder. Implications of
      the present investigation and future directions are discussed.

PMID- 24091304
TI  - The burden of cyclothymia on alcohol dependence.
AB  - BACKGROUND: The relationship between cyclothymic temperament and alcoholism
      remains insufficiently explored. METHODS: A sample of 125 alcohol-dependent
      patients diagnosed according to DSM-IV-TR criteria (APA, 2000) was recruited from
      a clinical setting. Cyclothymic temperament was diagnosed according to the
      Portuguese version of the Akiskal and Akiskal (2005) temperament scale. RESULTS:
      Alcohol dependent patients who score positive (above mean) for CT present to some
      extent a more severe profile of alcohol-related problems. LIMITATIONS:
      Correlational study CONCLUSIONS: CT traits in alcohol dependents seems to
      influence whether subjects engage earlier in pathological alcohol use and present
      particular alcohol-related problems, in particular Cloninger type II alcoholism
      phenotype.

PMID- 24091305
TI  - Family environment of bipolar families: a UK study.
AB  - BACKGROUND: Aspects of family environment (FE) such as family support,
      organisational structure and levels of conflict can increase risk of Bipolar
      Disorder (BD) in offspring of BD parents. METHODS: The family environment of 16
      BD and 23 healthy control (HC) families was assessed using the Family Environment
      Scale (FES). Canonical Correspondence Analysis (CCA) was used to determine the
      degree of variation in scores on the FES dimensions within each family and a
      Generalised Linear Modelling (GLM) approach was used to investigate the extent to
      which scores on the different FES dimensions differed between families. RESULTS:
      On the FES, BD families experienced an environment with higher levels of conflict
      and lower levels of expressiveness, organisation, intellectual-cultural
      orientation and active-recreational orientation than healthy control families.
      Differences in FES scores were driven by presence of parental BD and total number
      of children in the family. However, socio-economic status (SES) was not found to
      have an effect in this study. LIMITATIONS: As an American instrument the FES may
      not have been sensitive enough to the cultural context of a UK sample. The
      relatively small sample size used may have limited the statistical power of the
      study. CONCLUSIONS: Greater numbers of children have the same effect on levels of
      conflict as the presence of BD, while SES does not appear to be as important a
      factor in FE as previously thought. Our results suggest that family based
      interventions focusing on psychoeducation and improved communication within these
      families may address issues of conflict, organisation and expressiveness.

PMID- 24091306
TI  - Self-concept and quality of object relations as predictors of outcome in short-
      and long-term psychotherapy.
AB  - BACKGROUND: Quality of object relations and self-concept reflect clinically
      relevant aspects of personality functioning, but their prediction as suitability
      factors for psychotherapies of different lengths has not been compared. This
      study compared their prediction on psychiatric symptoms and work ability in short
      and long-term psychotherapy. METHODS: Altogether 326 patients, 20-46 years of
      age, with mood and/or anxiety disorder, were randomized to short-term (solution
      focused or short-term psychodynamic) psychotherapy and long-term psychodynamic
      psychotherapy. The Quality of Object Relations Scale (QORS) and the Structural
      Analysis of Social Behavior (SASB) self-concept questionnaire were measured at
      baseline, and their prediction on outcome during the 3-year follow-up was
      assessed by the Symptom Check List Global Severity Index and the Anxiety Scale,
      the Beck Depression Inventory and by the Work Ability Index, Social Adjustment
      Scale work subscale and the Perceived Psychological Functioning scale. RESULTS:
      Negative self-concept strongly and self-controlling characteristics modestly
      predicted better 3-year outcomes in long-term therapy, after faster early gains
      in short-term therapy. Patients with a more positive or self-emancipating self
      concept, or more mature object relations, experienced more extensive benefits
      after long-term psychotherapy. LIMITATIONS: The importance of length vs. long
      term therapy technique on the differences found is not known. CONCLUSIONS:
      Patients with mild to moderate personality pathology, indicated by poor self
      concept, seem to benefit more from long-term than short-term psychotherapy, in
      reducing risk of depression. Long-term therapy may also be indicated for patients
      with relatively good psychological functioning. More research is needed on the
      relative importance of these characteristics in comparison with other patient
      related factors.

PMID- 24091308
TI  - National surveillance of antimicrobial resistance among Gram-positive bacteria in
      Saudi Arabia.
AB  - BACKGROUND: Antimicrobial-resistant Gram-positive bacteria are important causes
      of serious infections. METHODS: Between January and December 2009, we examined
      clinical Gram-positive isolates from 24 hospitals across Saudi Arabia. RESULTS:
      Among the 13750 isolates, Staphylococcus aureus (62.3%) was the commonest,
      followed by non-group A beta-haemolytic streptococci (14.8%), group A beta
      haemolytic streptococci (7.1%), coagulase-negative staphylococci (6.6%),
      pneumococci (6.0%), and enterococci (3.1%). Resistance rates were high among S.
      aureus (methicillin-resistant S. aureus: 32%), coagulase-negative staphylococci
      (oxacillin: 63%) and pneumococci (penicillin G: 33%; erythromycin: 26%;
      ceftriaxone: 11%); low among enterococci (vancomycin: 1%) and among beta
      haemolytic streptococci. Resistance rates varied between regions, but comparison
      was complicated by differences in antibiotics tested. Many relevant antibiotics
      were tested against few isolates (e.g. ampicillin, vancomycin, and high-level
      gentamicin versus enterococci) while unhelpful tests were widely performed (e.g.
      cefotaxime, ceftriaxone, and imipenem versus staphylococci. CONCLUSION:
      Resistance is widespread in staphylococci and pneumococci, but not enterococci
      and beta-haemolytic streptococci in Saudi Arabia. Rationalization of antibiotic
      panels tested is urgently needed.

PMID- 24091307
TI  - Pharmacological distinction between soluble and transmembrane adenylyl cyclases.
AB  - The second messenger cAMP is involved in a number of cellular signaling pathways.
      In mammals, cAMP is produced by either the hormonally responsive, G protein
      regulated transmembrane adenylyl cyclases (tmACs) or by the bicarbonate- and
      calcium-regulated soluble adenylyl cyclase (sAC). To develop tools to
      differentiate tmAC and sAC signaling, we determined the specificity and potency
      of commercially available adenylyl cyclase inhibitors. In cellular systems, two
      inhibitors, KH7 and catechol estrogens, proved specific for sAC, and 2',5'
      dideoxyadenosine proved specific for tmACs. These tools provide a means to define
      the specific contributions of the different families of adenylyl cyclases in
      cells and tissues, which will further our understanding of cell signaling. 

PMID- 24091309
TI  - Glioma-derived macrophage migration inhibitory factor (MIF) promotes mast cell
      recruitment in a STAT5-dependent manner.
AB  - Recently, glioma research has increased its focus on the diverse types of cells
      present in brain tumors. We observed previously that gliomas are associated with
      a profound accumulation of mast cells (MCs) and here we investigate the
      underlying mechanism. Gliomas express a plethora of chemoattractants. First, we
      demonstrated pronounced migration of human MCs toward conditioned medium from
      cultures of glioma cell lines. Subsequent cytokine array analyses of media from
      cells, cultured in either serum-containing or -free conditions, revealed a number
      of candidates which were secreted in high amounts in both cell lines. Among
      these, we then focused on macrophage migration inhibitory factor (MIF), which has
      been reported to be pro-inflammatory and -tumorigenic. Infiltration of MCs was
      attenuated by antibodies that neutralized MIF. Moreover, a positive correlation
      between the number of MCs and the level of MIF in a large cohort of human glioma
      tissue samples was observed. Further, both glioma-conditioned media and purified
      MIF promoted differential phosphorylation of a number of signaling molecules,
      including signal transducer and activator of transcription 5 (STAT5), in MCs.
      Inhibition of pSTAT5 signaling significantly attenuated the migration of MCs
      toward glioma cell-conditioned medium shown to contain MIF. In addition, analysis
      of tissue microarrays (TMAs) of high-grade gliomas revealed a direct correlation
      between the level of pSTAT5 in MCs and the level of MIF in the medium. In
      conclusion, these findings indicate the important influence of signaling cascades
      involving MIF and STAT5 on the recruitment of MCs to gliomas. 

PMID- 24091310
TI  - Evaluation of new in vitro efficacy test for antimicrobial surface activity
      reflecting UK hospital conditions.
AB  - BACKGROUND: Antimicrobial surfaces aim to reduce microbial bioburden and improve
      hygiene. The current antimicrobial surface efficacy test (ISO22196) is an initial
      screening test but its conditions, high temperature (37 degrees C) and relative
      humidity (RH) (100%) bear little relationship to in-use conditions. AIM: To
      develop an antimicrobial surface efficacy test providing a realistic second-tier
      test, simulating in-use conditions. METHODS: Surface relative humidity,
      temperature and soiling were measured over one year at a UK hospital, enabling
      realistic parameters to be set for our surface efficacy test. A nebulizer,
      connected to a cascade impactor, aerosolized and uniformly deposited a
      Staphylococcus aureus suspension over test copper alloys and control stainless
      steel surfaces. Bacteria were enumerated following nebulization, and after a
      range of contact times, under [20 degrees C, 50% RH] and [20 degrees C, 40% RH]
      parameters reflecting in-use conditions; [37 degrees C, 100% RH] was employed to
      reflect conditions used in ISO22196. FINDINGS: All copper alloys produced a >4
      log10 reduction after 24h under all conditions tested. Copper alloys were more
      effective at [37 degrees C, 100% RH] showing a >4 log10 reduction after 30 min
      than at in-use conditions [20 degrees C, 50% RH and 20 degrees C, 40% RH], for
      which 60 min was required to achieve the same level of kill, for most but not all
      alloys. CONCLUSION: The use of the nebulizer to deposit bacterial inocula on
      surfaces showed little variability in results. Our method was more discriminatory
      than the ISO22196 enabling distinction between the bactericidal surface activity,
      which allows for a more rigorous selection of antimicrobial surfaces for
      potential use in healthcare settings.

PMID- 24091311
TI  - Safety and immunogenicity of the HPV-16/18 AS04-adjuvanted vaccine in HIV
      positive women in South Africa: a partially-blind randomised placebo-controlled
      study.
AB  - In developing countries, risk of human papillomavirus (HPV) infection may be
      increased by the high prevalence of human immunodeficiency virus (HIV) infection.
      We evaluated the safety and immunogenicity of the HPV-16/18 AS04-adjuvanted
      vaccine in HIV-infected women in South Africa. Asymptomatic HIV-positive women
      aged 18-25 years (N=120) were stratified by CD4+ T-cell count and randomised
      (1:1) to receive HPV-16/18 vaccine (Cervarix(r); GlaxoSmithKline Vaccines) or
      placebo (Al[OH]3) at 0, 1 and 6 months (double-blind). HIV-negative women (N=30)
      received HPV-16/18 vaccine (open label). Anti-HPV-16/18 antibody and CD4+ T-cell
      responses, CD4+ T-cell count, HIV viral load, HIV clinical stage and safety were
      evaluated for 12 months. The safety and reactogenicity profile of the HPV-16/18
      vaccine was comparable in HIV-positive and HIV-negative women. Irrespective of
      baseline HPV status, all HIV-positive and HIV-negative women who received the HPV
      16/18 vaccine were seropositive for both HPV-16 and HPV-18 after the second
      vaccine dose (month 2) and remained seropositive for both antigens at month 12.
      Anti-HPV-16/18 antibody titres at month 12 remained substantially above levels
      associated with natural infection. The HPV-16/18 vaccine induced sustained anti
      HPV-16/18 CD4+ T-cell responses in both HIV-positive and HIV-negative women. No
      impact of baseline CD4+ T-cell count or HIV viral load was observed on the
      magnitude of the immune response in HIV-positive women. In HIV-positive women,
      CD4+ T-cell count, HIV viral load and HIV clinical stage were unaffected by HPV
      16/18 vaccine administration. In conclusion, the HPV-16/18 AS04-adjuvanted
      vaccine appears immunogenic and well-tolerated in women with HIV infection. Study
      ID: 107863/NCT00586339.

PMID- 24091312
TI  - Immune responses of mice immunized by DNA plasmids encoding PCV2 ORF 2 gene,
      porcine IL-15 or the both.
AB  - Porcine circovirus type 2 (PCV2) is associated with many kinds of diseases
      including postweaning multisystemic wasting syndrome (PMWS). It affects the
      immune system of swine and causes huge epidemic losses every year. In our
      previous study, we provided evidence that DNA plasmid bearing porcine IL-15 (pVAX
      pIL-15) might serve as an immune enhancer for DNA plasmid encoding porcine
      reproductive and respiratory syndrome virus GP5 gene. In this study, PCV2 open
      reading frame (ORF)2 gene was cloned into the eukaryotic expression vector pVAX,
      resulting in the plasmid pVAX-PCV2-ORF2. Transient expression of the plasmid in
      BHK-21 cells could be detected using immunofluorescence assay. Experimental mice
      were divided into 5 groups and immunized with PBS, pVAX, pVAX-pIL-15, pVAX-PCV2
      ORF2 or pVAX-pIL-15 plus pVAX-PCV2-ORF2. The results showed that the mice co
      inoculated with pVAX-PCV2-ORF2 plus pVAX-pIL-15 had higher humoral and cellular
      immune responses than the others. In addition, DNA plasmid bearing PCV2 ORF2 gene
      had a protective effect against challenge with PCV2 in mice which could be
      promoted with the utilization of pIL-15. 

PMID- 24091313
TI  - Intranasal immunization with a non-adjuvanted adhesive protein descended from
      Pasteurella pneumotropica and its preventive efficacy against opportunistic
      infection in mice.
AB  - Intranasal vaccination is one of the most effective means of protecting against
      invading and colonizing pathogens because the vaccine elicits a mucosal immune
      response. The exploitation of vaccine adjuvants and delivery systems for
      intranasal vaccines is an important way to evoke antigen immunogenicity and
      elicit a better immune response at the mucosal sites. In the present study, we
      assessed the potential of intranasal immunization using a non-adjuvanted
      bacterial adhesive protein toward the host organs. We evaluated intranasal
      immunization with modified recombinant PnxIIIA (MP3) from Pasteurella
      pneumotropica and its preventive efficacy against opportunistic infection caused
      by P. pneumotropica, without using any adjuvants or delivery systems. The 100-kDa
      MP3 was confirmed to retain its immunogenicity and binding activity to collagen
      type I similar to the parent PnxIIIA. When MP3 was fused to green-fluorescent
      protein and inoculated into C57BL/6J mice intranasally, fluorescence intensity in
      the intranasal airway could be observed until 3 h after inoculation. Mice were
      intranasally immunized with MP3 at a maximum of 4 doses, with 7-day intervals.
      The antibody titer of serum IgG and IgA specific for MP3, as well as that of
      bronchoalveolar lavage fluid IgA, showed more than 9 (log2) after 3 or 4 rounds
      of immunization. Experimentally infecting immunized mice with P. pneumotropica
      resulted in the inability to isolate the bacterium from the nasal cavity,
      trachea, conjunctiva, or cecum with more than 3 doses in the immunized mice.
      Although the detection in each organ seldom changed with less than 2 rounds of
      immunization, unlike that observed in the non-immunized mice, the detection
      remarkably decreased with 3 or more rounds of immunization. These results suggest
      that intranasal immunization with a non-adjuvanted adhesive protein could have
      preventive effects against opportunistic infection by P. pneumotropica.

PMID- 24091314
TI  - High prevalence of allergy in North Cypriot children.
AB  - BACKGROUND: The ISAAC (the International Study of Asthma and Allergies in
      Childhood) questionnaire has been used to standardize research on the prevalence
      of asthma in children since 1991. AIM: In this Phase I study, the prevalence of
      asthma, other allergic diseases and atopy was evaluated in North Cyprus. METHODS:
      The ISAAC questionnaire was distributed to grades I-V schoolchildren. Data were
      obtained from parents of 580 schoolchildren aged between 7 and 12 years attending
      a primary school in Nicosia, the capital of North Cyprus. Of those, a sub-group
      of 97 (16.7%) randomly selected children were evaluated by skin prick test (SPT)
      and lung function test (LFT). RESULTS: The prevalence rates of asthma ever,
      current wheezing and SPT-positivity were 20.8%, 10% and 68%, respectively. The
      prevalence of atopy was significantly higher in the randomly selected subgroup of
      97 (68%) patients subjected to SPT and LFT, and the house dust mite (HDM) was the
      allergen to which children were most frequently sensitized. CONCLUSIONS: In
      northern Cyprus, the prevalence rates of asthma, allergic diseases and atopic
      sensitization in 7-12-year-old children are extremely high. Sensitization to HDM
      is a risk factor for the development of asthma.

PMID- 24091315
TI  - Association of Anthropometric indexes with chronic kidney disease in a Chinese
      population.
AB  - OBJECTIVE: Obesity is associated with an increased risk of chronic kidney disease
      (CKD), but the best anthropometric obesity measure remains controversial. This
      study aimed to examine the associations of anthropometric indexes with CKD risk
      and which anthropometric index is a better predictor of CKD. METHODS: Data was
      drawn from a cross-sectional study in China. We used four anthropometric indexes:
      body mass index (BMI), waist circumference (WC), waist-to hip ratio (WHR), and
      waist-to-height ratio (WHtR). CKD was defined as estimated glomerular filtration
      rate (eGFR) < 60 ml/ min/1.73 m2 or urinary albumin to creatinine ratio (ACR) >=
      30 mg/g. Logistic regressions were used for the analyses. RESULTS: 1,834
      participants were included in the analyses. After adjusting for potential
      confounders, BMI, WC and WHtR were significantly associated with CKD in men and
      women. The respective odd ratios for BMI (every SD increment), WC (every SD
      increment), and WHtR (every SD increment) were 1.46, 1.40, and 1.45 in men as
      well as 1.21, 1.31, and 1.38 in women. After adjusting for potential confounders,
      WHR was associated with CKD in women but not men. In women, the associations of
      WC, WHR and WHtR with CKD was independent of other MetS components. No difference
      in WHtR was observed between men and women. CONCLUSION: Anthropometric indexes
      are associated with CKD. The associations of anthropometric indexes with CKD are
      independent of other MetS components in women but not men. In women, central
      obesity indexes are better than BMI for predicting of CKD.

PMID- 24091316
TI  - Serum osteoprotegerin level is associated with degree of arteriovenous fistula
      stenosis in patients with hemodialysis.
AB  - AIMS: Vascular access dysfunction caused by stenosis is a major complication for
      hemodialysis (HD) patients. However, the relevant humoral mediators of
      arteriovenous (AV) access stenosis are still under investigation. The aim of the
      present study was to evaluate the association between serum fetuin-A,
      osteoprotegerin (OPG), and heat shock protein (Hsp) 70 concentration with
      arteriovenous fistula (AVF) patency in HD patients. METHODS: Serum fetuin-A, OPG
      and Hsp70 concentrations were measured in 64 HD patients. Using these data, we
      studied the association of fetuin-A, OPG and Hsp70 with the degree of AVF
      stenosis using ultrasonography in HD patients. RESULTS: The degree of AVF
      stenosis was positively correlated with OPG levels (r = 0.411, p = 0.001) and
      OPG/fetuin-A ratio (r = 0.375, p = 0.002). The levels of OPG and OPG/fetuin-A
      ratio were statistically higher in the group of AVF stenosis >= 11.5%. Stepwise
      linear regression analyses independently predicted the degree of AVF stenosis on
      the logarithmic function of the OPG (beta = 8.775, standard error = 0.493, p =
      0.034) and OPG/fetuin-A ratio (beta = 10.325, standard error = 3.247, p = 0.018).
      CONCLUSIONS: Our data demonstrated that OPG and the OPG/fetuin-A ratio correlated
      with the degree of AVF stenosis in HD patients. In addition, OPG and the
      OPG/fetuin-A ratio were the most important predictors of the degree of AVF
      stenosis in HD patients.

PMID- 24091317
TI  - The influence of socioeconomic factors on depression in maintenance hemodialysis
      patients and their caregivers.
AB  - AIM: A Depression has a strong impact on the quality of life of patients
      receiving maintenance hemodialysis (MHD). The objective of this study was to
      analyze the factors influencing the depression scores of MHD patients and their
      primary caregivers. METHODS: 141 patients (54 female, aged 53.6 +/- 14.2 years)
      who had been on MHD for at least 3 months were included. Age, gender, etiology of
      renal disease, duration of dialysis, marital and employment status, and income
      and living status of patients were recorded from patient charts and through face
      to-face interviews. Disability was assessed by a selfadministered questionnaire.
      Additionally, 40 of the 141 patients (28%) primary caregivers were interviewed
      face-to-face. All patients and 40 primary caregivers were evaluated for the
      presence of depressive symptoms by Beck Depression Inventory (BDI). RESULTS:
      Moderate to severe depressive symptoms were found in 36.2% of the study group.
      Divorced patients were significantly more depressed (p < 0.02) than married or
      single patients. Patients living with and being cared for by their nuclear family
      (father, mother, and/or children) were less depressed than patients being cared
      for by other relatives (p < 0.009). Monthly income was negatively correlated with
      both patients' and primary caregivers' BDI score (p < 0.005). Patients with high
      disability scores were more depressed than nondisabled patients (p < 0.08).
      Primary caregivers' BDI scores were positively correlated with the patients' BDI
      scores (p < 0.0001). Binary logistic regression analysis revealed that higher
      depression scores were significantly associated with more than 3 children under
      guardianship (p < 0.01) and higher disability scores (p < 0.023). CONCLUSION: In
      this present study, we observed that economically, socially, and physically self
      sufficient MHD patients had lower depression rates. The treatment of depression
      and social and psychological support for both the patient and the family members
      are essential for better medical status among MHD patients.

PMID- 24091318
TI  - Does enteral protein intake affect renal glomerular and tubular functions in very
      low birth weight infants?
AB  - OBJECTIVES AND AIM: Very low birth weight infants require 3 - 4 g/kg/day protein
      intake to provide satisfactory postnata growth rates and neurodevelopmental
      outcomes. However, they have fewer functional nephrons, thereby increasing
      vulnerability for impaired renal functions. The aim of this study was to
      investigate the effect of different amounts of enteral protein intake during the
      fortification of human milk on renal glomerular and tubular functions. MATERIAL
      AND METHODS: Preterm infants were randomized into three groups in terms of their
      daily protein intake: standard fortification (3 g/kg/d), moderate fortification
      (3.3 g/kg/d), and aggressive fortification (3.6 g/kg/d). Serum urea, creatinine
      (Cr), Cystatin C (Cys-C) and urinary beta2 microglobulin (beta2M) levels were
      assessed and compared between groups. RESULTS: Serum urea, Cr, Cys-C and urinary
      beta2M levels were similar in all three groups, both on discharge and postnatal
      Day 14 (p > 0.05). Mean Cr and beta2M levels were significantly lower on
      discharge (p < 0.05), while Cys-C levels did not differ in time (p > 0.05).
      CONCLUSION: Enteral protein intake up to 3.6 g/kg/d did not alter the tubular and
      glomerular functions in very preterm infants. However, the long-term renal
      effects in these infants maintained on a high protein intake remain unknown and
      should be addressed in future studies.

PMID- 24091319
TI  - Richard Scheller and Thomas Sudhof receive the 2013 Albert Lasker Basic Medical
      Research Award.

PMID- 24091320
TI  - Hearing restoration: Graeme Clark, Ingeborg Hochmair, and Blake Wilson receive
      the 2013 Lasker~DeBakey Clinical Medical Research Award.

PMID- 24091321
TI  - Bill and Melinda Gates honored with Lasker~Bloomberg Public Service Award.

PMID- 24091322
TI  - ACTN3 genotype influences muscle performance through the regulation of
      calcineurin signaling.
AB  - alpha-Actinin-3 deficiency occurs in approximately 16% of the global population
      due to homozygosity for a common nonsense polymorphism in the ACTN3 gene. Loss of
      alpha-actinin-3 is associated with reduced power and enhanced endurance capacity
      in elite athletes and nonathletes due to "slowing" of the metabolic and
      physiological properties of fast fibers. Here, we have shown that alpha-actinin-3
      deficiency results in increased calcineurin activity in mouse and human skeletal
      muscle and enhanced adaptive response to endurance training. alpha-Actinin-2,
      which is differentially expressed in alpha-actinin-3-deficient muscle, has higher
      binding affinity for calsarcin-2, a key inhibitor of calcineurin activation. We
      have further demonstrated that alpha-actinin-2 competes with calcineurin for
      binding to calsarcin-2, resulting in enhanced calcineurin signaling and
      reprogramming of the metabolic phenotype of fast muscle fibers. Our data provide
      a mechanistic explanation for the effects of the ACTN3 genotype on skeletal
      muscle performance in elite athletes and on adaptation to changing physical
      demands in the general population. In addition, we have demonstrated that the
      sarcomeric alpha-actinins play a role in the regulation of calcineurin signaling.

PMID- 24091323
TI  - Maternal uterine NK cell-activating receptor KIR2DS1 enhances placentation.
AB  - Reduced trophoblast invasion and vascular conversion in decidua are thought to be
      the primary defect of common pregnancy disorders including preeclampsia and fetal
      growth restriction. Genetic studies suggest these conditions are linked to
      combinations of polymorphic killer cell Ig-like receptor (KIR) genes expressed by
      maternal decidual NK cells (dNK) and HLA-C genes expressed by fetal trophoblast.
      Inhibitory KIR2DL1 and activating KIR2DS1 both bind HLA-C2, but confer increased
      risk or protection from pregnancy disorders, respectively. The mechanisms
      underlying these genetic associations with opposing outcomes are unknown. We show
      that KIR2DS1 is highly expressed in dNK, stimulating strong activation of
      KIR2DS1+ dNK. We used microarrays to identify additional responses triggered by
      binding of KIR2DS1 or KIR2DL1 to HLA-C2 and found different responses in dNK
      coexpressing KIR2DS1 with KIR2DL1 compared with dNK only expressing KIR2DL1.
      Activation of KIR2DS1+ dNK by HLA-C2 stimulated production of soluble products
      including GM-CSF, detected by intracellular FACS and ELISA. We demonstrated that
      GM-CSF enhanced migration of primary trophoblast and JEG-3 trophoblast cells in
      vitro. These findings provide a molecular mechanism explaining how recognition of
      HLA class I molecules on fetal trophoblast by an activating KIR on maternal dNK
      may be beneficial for placentation. 

PMID- 24091324
TI  - Integrins protect cardiomyocytes from ischemia/reperfusion injury.
AB  - Ischemic damage is recognized to cause cardiomyocyte (CM) death and myocardial
      dysfunction, but the role of cell-matrix interactions and integrins in this
      process has not been extensively studied. Expression of alpha7beta1D integrin,
      the dominant integrin in normal adult CMs, increases during ischemia/reperfusion
      (I/R), while deficiency of beta1 integrins increases ischemic damage. We
      hypothesized that the forced overexpression of integrins on the CM would offer
      protection from I/R injury. Tg mice with CM-specific overexpression of integrin
      alpha7beta1D exposed to I/R had a substantial reduction in infarct size compared
      with that of alpha5beta1D-overexpressing mice and WT littermate controls. Using
      isolated CMs, we found that alpha7beta1D preserved mitochondrial membrane
      potential during hypoxia/reoxygenation (H/R) injury via inhibition of
      mitochondrial Ca2+ overload but did not alter H/R effects on oxidative stress.
      Therefore, we assessed Ca2+ handling proteins in the CM and found that beta1D
      integrin colocalized with ryanodine receptor 2 (RyR2) in CM T-tubules, complexed
      with RyR2 in human and rat heart, and specifically bound to RyR2 amino acids 165
      175. Integrins stabilized the RyR2 interdomain interaction, and this
      stabilization required integrin receptor binding to its ECM ligand. These data
      suggest that alpha7beta1D integrin modifies Ca2+ regulatory pathways and offers a
      means to protect the myocardium from ischemic injury. 

PMID- 24091325
TI  - 2-Aminoadipic acid is a biomarker for diabetes risk.
AB  - Improvements in metabolite-profiling techniques are providing increased breadth
      of coverage of the human metabolome and may highlight biomarkers and pathways in
      common diseases such as diabetes. Using a metabolomics platform that analyzes
      intermediary organic acids, purines, pyrimidines, and other compounds, we
      performed a nested case-control study of 188 individuals who developed diabetes
      and 188 propensity-matched controls from 2,422 normoglycemic participants
      followed for 12 years in the Framingham Heart Study. The metabolite 2-aminoadipic
      acid (2-AAA) was most strongly associated with the risk of developing diabetes.
      Individuals with 2-AAA concentrations in the top quartile had greater than a 4
      fold risk of developing diabetes. Levels of 2-AAA were not well correlated with
      other metabolite biomarkers of diabetes, such as branched chain amino acids and
      aromatic amino acids, suggesting they report on a distinct pathophysiological
      pathway. In experimental studies, administration of 2-AAA lowered fasting plasma
      glucose levels in mice fed both standard chow and high-fat diets. Further, 2-AAA
      treatment enhanced insulin secretion from a pancreatic beta cell line as well as
      murine and human islets. These data highlight a metabolite not previously
      associated with diabetes risk that is increased up to 12 years before the onset
      of overt disease. Our findings suggest that 2-AAA is a marker of diabetes risk
      and a potential modulator of glucose homeostasis in humans. 

PMID- 24091326
TI  - Radiation-induced acid ceramidase confers prostate cancer resistance and tumor
      relapse.
AB  - Escape of prostate cancer (PCa) cells from ionizing radiation-induced (IR
      induced) killing leads to disease progression and cancer relapse. The influence
      of sphingolipids, such as ceramide and its metabolite sphingosine 1-phosphate, on
      signal transduction pathways under cell stress is important to survival
      adaptation responses. In this study, we demonstrate that ceramide-deacylating
      enzyme acid ceramidase (AC) was preferentially upregulated in irradiated PCa
      cells. Radiation-induced AC gene transactivation by activator protein 1 (AP-1)
      binding on the proximal promoter was sensitive to inhibition of de novo ceramide
      biosynthesis, as demonstrated by promoter reporter and ChIP-qPCR analyses. Our
      data indicate that a protective feedback mechanism mitigates the apoptotic effect
      of IR-induced ceramide generation. We found that deregulation of c-Jun induced
      marked radiosensitization in vivo and in vitro, which was rescued by ectopic AC
      overexpression. AC overexpression in PCa clonogens that survived a fractionated
      80-Gy IR course was associated with increased radioresistance and proliferation,
      suggesting a role for AC in radiotherapy failure and relapse. Immunohistochemical
      analysis of human PCa tissues revealed higher levels of AC after radiotherapy
      failure than those in therapy-naive PCa, prostatic intraepithelial neoplasia, or
      benign tissues. Addition of an AC inhibitor to an animal model of xenograft
      irradiation produced radiosensitization and prevention of relapse. These data
      indicate that AC is a potentially tractable target for adjuvant radiotherapy. 

PMID- 24091327
TI  - Pak and Rac GTPases promote oncogenic KIT-induced neoplasms.
AB  - An acquired somatic mutation at codon 816 in the KIT receptor tyrosine kinase is
      associated with poor prognosis in patients with systemic mastocytosis and acute
      myeloid leukemia (AML). Treatment of leukemic cells bearing this mutation with an
      allosteric inhibitor of p21-activated kinase (Pak) or its genetic inactivation
      results in growth repression due to enhanced apoptosis. Inhibition of the
      upstream effector Rac abrogates the oncogene-induced growth and activity of Pak.
      Although both Rac1 and Rac2 are constitutively activated via the guanine
      nucleotide exchange factor (GEF) Vav1, loss of Rac1 or Rac2 alone moderately
      corrected the growth of KIT-bearing leukemic cells, whereas the combined loss
      resulted in 75% growth repression. In vivo, the inhibition of Vav or Rac or Pak
      delayed the onset of myeloproliferative neoplasms (MPNs) and corrected the
      associated pathology in mice. To assess the role of Rac GEFs in oncogene-induced
      transformation, we used an inhibitor of Rac, EHop-016, which specifically targets
      Vav1 and found that EHop-016 was a potent inhibitor of human and murine leukemic
      cell growth. These studies identify Pak and Rac GTPases, including Vav1, as
      potential therapeutic targets in MPN and AML involving an oncogenic form of KIT. 

PMID- 24091328
TI  - Myeloid-derived suppressor cell development is regulated by a STAT/IRF-8 axis.
AB  - Myeloid-derived suppressor cells (MDSCs) comprise immature myeloid populations
      produced in diverse pathologies, including neoplasia. Because MDSCs can impair
      antitumor immunity, these cells have emerged as a significant barrier to cancer
      therapy. Although much research has focused on how MDSCs promote tumor
      progression, it remains unclear how MDSCs develop and why the MDSC response is
      heavily granulocytic. Given that MDSCs are a manifestation of aberrant
      myelopoiesis, we hypothesized that MDSCs arise from perturbations in the
      regulation of interferon regulatory factor-8 (IRF-8), an integral transcriptional
      component of myeloid differentiation and lineage commitment. Overall, we
      demonstrated that (a) Irf8-deficient mice generated myeloid populations highly
      homologous to tumor-induced MDSCs with respect to phenotype, function, and gene
      expression profiles; (b) IRF-8 overexpression in mice attenuated MDSC
      accumulation and enhanced immunotherapeutic efficacy; (c) the MDSC-inducing
      factors G-CSF and GM-CSF facilitated IRF-8 downregulation via STAT3- and STAT5
      dependent pathways; and (d) IRF-8 levels in MDSCs of breast cancer patients
      declined with increasing MDSC frequency, implicating IRF-8 as a negative
      regulator in human MDSC biology. Together, our results reveal a previously
      unrecognized role for IRF-8 expression in MDSC subset development, which may
      provide new avenues to target MDSCs in neoplasia. 

PMID- 24091329
TI  - Inhibiting glycolytic metabolism enhances CD8+ T cell memory and antitumor
      function.
AB  - Naive CD8+ T cells rely upon oxidation of fatty acids as a primary source of
      energy. After antigen encounter, T cells shift to a glycolytic metabolism to
      sustain effector function. It is unclear, however, whether changes in glucose
      metabolism ultimately influence the ability of activated T cells to become long
      lived memory cells. We used a fluorescent glucose analog, 2-NBDG, to quantify
      glucose uptake in activated CD8+ T cells. We found that cells exhibiting limited
      glucose incorporation had a molecular profile characteristic of memory precursor
      cells and an increased capacity to enter the memory pool compared with cells
      taking up high amounts of glucose. Accordingly, enforcing glycolytic metabolism
      by overexpressing the glycolytic enzyme phosphoglycerate mutase-1 severely
      impaired the ability of CD8+ T cells to form long-term memory. Conversely,
      activation of CD8+ T cells in the presence of an inhibitor of glycolysis, 2
      deoxyglucose, enhanced the generation of memory cells and antitumor
      functionality. Our data indicate that augmenting glycolytic flux drives CD8+ T
      cells toward a terminally differentiated state, while its inhibition preserves
      the formation of long-lived memory CD8+ T cells. These results have important
      implications for improving the efficacy of T cell-based therapies against chronic
      infectious diseases and cancer. 

PMID- 24091330
TI  - p16(INK4a) protects against dysfunctional telomere-induced ATR-dependent DNA
      damage responses.
AB  - Dysfunctional telomeres limit cellular proliferative capacity by activating the
      p53-p21- and p16(INK4a)-Rb-dependent DNA damage responses (DDRs). The p16(INK4a)
      tumor suppressor accumulates in aging tissues, is a biomarker for cellular
      senescence, and limits stem cell function in vivo. While the activation of a p53
      dependent DDR by dysfunctional telomeres has been well documented in human cells
      and mouse models, the role for p16(INK4a) in response to telomere dysfunction
      remains unclear. Here, we generated protection of telomeres 1b p16-/- mice
      (Pot1bDelta/Delta;p16-/-) to address the function of p16(INK4a) in the setting of
      telomere dysfunction in vivo. We found that deletion of p16(INK4a) accelerated
      organ impairment and observed functional defects in highly proliferative organs,
      including the hematopoietic system, small intestine, and testes.
      Pot1bDelta/Delta;p16-/- hematopoietic cells exhibited increased telomere loss,
      increased chromosomal fusions, and telomere replication defects. p16(INK4a)
      deletion enhanced the activation of the ATR-dependent DDR in Pot1bDelta/Delta
      hematopoietic cells, leading to p53 stabilization, increased p21-dependent cell
      cycle arrest, and elevated p53-dependent apoptosis. In contrast to p16(INK4a),
      deletion of p21 did not activate ATR, rescued proliferative defects in
      Pot1bDelta/Delta hematopoietic cells, and significantly increased organismal
      lifespan. Our results provide experimental evidence that p16(INK4a) exerts
      protective functions in proliferative cells bearing dysfunctional telomeres.

PMID- 24091332
TI  - In vitro efficacy of various topical antimicrobial agents in different time
      periods from contamination to application against 6 multidrug-resistant bacterial
      strains isolated from burn patients.
AB  - AIM: In vitro efficacy evaluation of eleven topical antimicrobials against
      multidrug-resistant (MDR) bacteria isolated from burn wounds of our patients.
      MATERIAL AND METHODS: Growth of six MDR bacterial strains: Pseudomonas aeruginosa
      (2 strains), Staphylococcus aureus, Staphylococcus haemolyticus, Enterococcus
      faecalis and Escherichia coli in burn-wound models was evaluated 24-h after
      application of the tested agents. Four different wound models were created to
      investigate the role of time elapsed between inoculation of bacteria and
      application of the agents on their antimicrobial activity and efficacy. RESULTS:
      The efficacy against all the 6 bacteria in freshly contaminated wounds was
      excellent in majority of the tested agents. The longer was the time interval
      between inoculation and application of the topical antimicrobial agents, the
      higher failure of the agents was observed. CONCLUSIONS: Topical antimicrobials
      play an important role in treatment of burn wounds, but they should be used
      according to their efficacy against bacterial strains present in patients'
      wounds. In cases where topical agents have been applied after 24 h, when
      formation of mature biofilm in the wound could be expected, it would probably not
      be possible to kill all the bacteria using topical antimicrobial therapy only.

PMID- 24091331
TI  - Blood pressure homeostasis is maintained by a P311-TGF-beta axis.
AB  - P311 is an 8-kDa intracellular protein that is highly conserved across species
      and is expressed in the nervous system as well as in vascular and visceral smooth
      muscle cells. P311-null (P311-/-) mice display learning and memory defects, but
      alterations in their vasculature have not been previously described. Here we
      report that P311-/- mice are markedly hypotensive with accompanying defects in
      vascular tone and VSMC contractility. Functional abnormalities in P311-/- mice
      resulted from decreased total and active levels of TGF-beta1, TGF-beta2, and TGF
      beta3 that arise as a specific consequence of decreased translation. Vascular
      hypofunctionality was fully rescued in vitro and in vivo by exogenous TGF-beta1
      TGF-beta3. Conversely, P311-transgenic (P311(TG)) mice had elevated levels of TGF
      beta1-TGF-beta3 and subsequent hypertension. Consistent with findings attained in
      mouse models, arteries recovered from hypertensive human patients displayed
      increased P311 expression. Thus, we identified P311 as the first protein known to
      modulate TGF-beta translation and the first pan-regulator of TGF-beta expression
      under steady-state conditions. Together, our findings point to P311 as a critical
      blood pressure regulator and establish a potential link between P311 expression
      and the development of hypertensive disease.

PMID- 24091333
TI  - [Scores and stages].

PMID- 24091334
TI  - [The use of scores in general medicine].
AB  - Scores are tools to combine complex information into a numerical value. In
      General Medicine, there are scores to assist in making diagnoses and prognoses,
      scores to assist therapeutic decision making and to evaluate therapeutic results
      and scores to help physicians when informing and advising patients. We review six
      of the scoring systems that have the greatest utility for the General Physician
      in hospital-based care and in General Practice. The Nutritional Risk Screening
      (NRS 2002) tool is designed to identify hospital patients in danger of
      malnutrition. The aim is to improve the nutritional status of these patients. The
      CURB-65 score predicts 30-day mortality in patients with community acquired
      pneumonia. Patients with a low score can be considered for home treatment,
      patients with an elevated score require hospitalisation and those with a high
      score should be treated as having severe pneumonia; treatment in the intensive
      care unit should be considered. The IAS-AGLA score of the Working Group on Lipids
      and Atherosclerosis of the Swiss Society of Cardiology calculates the 10-year
      risk of a myocardial infarction for people living in Switzerland. The working
      group makes recommendations for preventative treatment according to the
      calculated risk status. The Body Mass Index, which is calculated by dividing the
      body weight in kilograms by the height in meters squared and then divided into
      weight categories, is used to classify people as underweight, of normal weight,
      overweight or obese. The prognostic value of this classification is discussed.
      The Mini-Mental State Examination allows the physician to assess important
      cognitive functions in a simple and standardised form. The Glasgow Coma Scale is
      used to classify the level of consciousness in patients with head injury. It can
      be used for triage and correlates with prognosis. 

PMID- 24091335
TI  - [Scores and stages in angiology].
AB  - For the classification of peripheral arterial disease the Fontaine's stages are
      mostly used in Switzerland whereas the Rutherford's categories are more common in
      the scientific literature. It is important to distinguish between the Rutherford
      classification for chronic peripheral artery disease and the one for the acute
      limb ischemia. The clinical classification of acute limb ischemia is a helpful
      tool for prognosis of the leg and urgency of revascularization. The Wagner as
      well as the Armstrong classification is used for diabetic foot ulcers. The
      advantage of the Armstrong stages is that important informations like wound
      infection or ischemia are considered. For chronic venous insufficiency the Widmer
      stages are widely used in Switzerland but have the disadvantage that patient
      reported symptom severity is not considered. The CEAP classification includes
      anatomical information and the etiology and is mostly used for studies. The Wells
      score helps to define the probability for the presence of a deep vein thrombosis
      before further tests are performed. 

PMID- 24091336
TI  - [Scores and stages in gastroenterology].
AB  - Staging and grading are indispensable in clinical gastroenterology in order to
      determine disease activity or therapeutic outcomes in a systematic and
      reproducible way. Adequate diagnosis, patient care and appropriate therapy will
      often depend on accurate staging and grading. Some of the most commonly
      encountered diseases in clinical gastroenterology and gastrointestinal endoscopy
      are gastroesophageal reflux disease, peptic ulcer disease, gastrointestinal
      vascular disorders such as hemorrhoids and esophageal varices as well as
      inflammatory bowel diseases. Some of the clinically most useful pertinent indices
      are summarized in this section. 

PMID- 24091337
TI  - [Hepatology scores].
AB  - We are performing a complex medicine in an environment of limited resources.
      Therefore we need to accurately diagnose, predict and treat. Many scores have
      been developed with these goals in Hepatology. We choose to limit our attention
      to those widely used and established which are really decisive in daily clinical
      management: the Child-Pugh-Turcotte-Score (CTP); the MELD-Score, the simplified
      criteria for the diagnosis of autoimmune hepatitis, the Mayo-Score for primary
      biliary cirrhosis and the Lille-Score for alcoholic hepatitis. All scores use
      clinical features as well as laboratory findings to make these statements. It is
      likely that these scores will remain in clinical practice for many more years
      even if new scores based on molecular signatures may be introduced in a near
      future. 

PMID- 24091338
TI  - [Important classifications and scores in cardiology].
AB  - Classifications and scores play a fundamental role in clinical cardiology. While
      classification systems may help to quantify symptoms and stages of disease,
      specific scores enable risk stratification and may facilitate decision-making in
      various cardiac disorders. The present article reviews some of the most
      frequently used cardiologic classifications and scores. Frequently used
      classification systems are the NYHA classification for staging patients with
      cardiac diseases according to their symptoms and functional capacity, and the CCS
      classification for grading the severity of symptoms in patients with stable
      angina pectoris. The Killip classification represents a simple clinical tool to
      estimate mortality risk in patients with acute coronary syndromes. While there is
      no controversy about the acute management of patients with STEMI - i. e.
      reperfusion therapy by fibrinolysis or, preferably, primary percutaneous coronary
      intervention - the diagnostic and therapeutic strategy in patients with NSTE-ACS
      depends on their individual risk. Various scores have been developed for early
      risk stratification in patients with NSTE-ACS. Of these, the TIMI risk score and
      the GRACE score are the most frequently used. Prevention of thromboembolic events
      represents a primary therapeutic goal in patients with atrial fibrillation. In
      affected patients, scores such as the CHA2DS2-VASc-Score and the HAS-BLED score
      are helpful in assessing individual risk of thromboembolic and bleeding
      complications. Herewith, these scores aid in decision-making for anticoagulation
      and, thereby, improve prognosis of patients with atrial fibrillation. 

PMID- 24091339
TI  - [Scores and stages in nephrology].
AB  - In this article we review the most relevant acronyms, scores and classifications
      in the fields of nephrology and urology, including the newest definitions of
      acute kidney injury and chronic kidney diseases. We will also present a short
      overview of the histopathological Lupus nephritis classification, the renal cysts
      Bosniak classification and the vesicoureteral reflux grading. 

PMID- 24091340
TI  - [Scores and stages in neurology].
AB  - Neurological scores and stages are helpful for quantifying functional deficits
      and describing neurological disorders in a standardized way. These assessments
      may support evidence-based diagnostic or therapeutic decisions-making and
      accurate evaluation of treatment options. Unfortunately most of the frequently
      used scores and stages in neurology do not fulfill the quality requirements in
      respect of reliability, validity and responsiveness (sensitivity, specifity). On
      the other hand, more valid assessments are often limited by their complexity and
      high expenditure of time. In addition even complex scores are describing only
      limited aspects of disorders sometimes mixing different domains of health.
      Accurate clinical observation and precise narrative description of clinical
      phenomena and diseases therefore remains an important task in comprehensive
      recording and presentation or neurological disorders. 

PMID- 24091341
TI  - [From Gleason score to Ann Arbor staging- a selective choice of important scores
      and staging systems in oncology].
AB  - Hundreds scores and dozens staging systems exist in Oncology. They provide for
      example information on the spread and prognosis of a disease or are included in
      treatment decisions. Because of the existing diversity a description of all
      oncological codes would exceed the scope of this paper, the following articles
      focuses in the first part on some exemplary and lesser-known scores and in the
      second part on main staging systems in Oncology. Internet sites such as Wikipedia
      or Onkopedia provide answers to many other questions regarding ongologic scores
      and stages. As an example of a tumor graduation the Gleason score in prostate
      cancer is described. It provides not only information about the prognosis of the
      disease, but influences the primary treatment. In metastasic disease, the general
      condition of the patient is decisive on the question of whether a (further)
      systemic therapy should be applied. The general condition is classified with the
      Karnofsky index and in Oncology more frequently with the ECOG- or WHO-performance
      status. In solid tumors the response to treatment is assessed with RECIST
      criteria. The spread of solid malignancies is documented according to the TNM
      classification. This classification is regularly updated according to latest
      prognostic and therapeutic results. In contrast the Ann Arbor criterias - the
      staging system of lymphomas - have little changed since their initial
      description. 

PMID- 24091342
TI  - [Scores and stages in pneumology].
AB  - Useful scales and classifications for patients with pulmonary diseases are
      discussed. The modified Medical Research Council breathlessness scale (mMRC) is a
      measure of disability in lung patients. The GOLD classifications, the COPD
      Assessment Test (CAT) and the BODE Index are important to classify the severity
      of COPD and to measure the disability of these patients. The Geneva score is a
      clinical prediction rule used in determining the pre-test probability of
      pulmonary embolism. The Pulmonary Embolism Severity Index (PESI) is a scoring
      system used to predict 30 day mortality in patients with pulmonary embolism. The
      Epworth Sleepiness Scale is intended to measure daytime sleepiness in patients
      with sleep apnea syndrome. The Asthma Controll Test (ACT) determines if asthma
      symptoms are well controlled. 

PMID- 24091344
TI  - Catalytic degradation of methylene blue using biosynthesized gold and silver
      nanoparticles.
AB  - The scientific community is searching for new synthesis methods for the
      production of metallic nanoparticles. Green synthesis has now become a vast
      developing area of research. Here we report for the first time to best of our
      knowledge, a new green method for the synthesis of silver and gold nanoparticles
      using the Kashayam, Guggulutiktham, an ayurvedic medicine. This method is
      nontoxic and environmentally benign. The reduction and the stabilization capacity
      of the ayurvedic Kashayam are described in this paper. The size and shape of the
      silver and gold nanoparticles can be tuned by varying the quantity of the
      Kashayam. The synthesized nanoparticles are characterized using UV-VIS
      spectroscopy, TEM, XRD and FTIR. The size dependent catalytic activity of the
      synthesized nanoparticles is established in the reduction of Methylene Blue (MB)
      by NaBH4. 

PMID- 24091345
TI  - Complexation, thermal and catalytic studies of N-substituted piperazine,
      morpholine and thiomorpholine with some metal ions.
AB  - Several Cu(II), Pt(II) and Ni(II) complexes of N-substituted, piperazine (NN
      donor), morpholine (NO donor) and thiomorpholine (NS donor) derivatives were
      synthesized and their thermal behavior and catalytic activity in epoxidation
      reaction of cis-diphenylethylene were studied using oxygen sources NaOCl. The
      coordination compounds of Cu(II), Pt(II) and Ni(II) having general formula
      [MLCl]Cl, [ML2l]Cl2 or [ML]Cl2 with tetra coordinated geometry around metal ions
      have been isolated as solid. All the ligands and complexes were identified by
      spectroscopic methods and elemental analysis, magnetic measurements, electrical
      conductance and thermal analysis. A square planer structures have been proposed
      for all complexes. The thermal stability of the complexes discussed in terms of
      ligands donor atoms, geometry and central metal ions. The complexes have a
      similar thermal behavior for the selected metal ions. The thermogravimetric
      analyses suggest high thermal stability for most complexes followed by thermal
      decomposition in different steps. The decomposition processes were observed as
      water elimination, chloride anion removal and degradation of the organic ligands.
      Catalytic ability of the complexes were examined and found that all the complexes
      can effectively catalyze the epoxidation of cis-stilbene with NaOCl. 

PMID- 24091346
TI  - Structure, crystal growth, optical and mechanical studies of poly bis (thiourea)
      silver (I) nitrate single crystal: a new semi organic NLO material.
AB  - A new semi organic non linear optical polymeric crystal, bis (thiourea) silver
      (I) nitrate (TuAgN) with dimension 8*7*1.5 mm(3) has been successfully grown from
      aqueous solution by slow evaporation solution technique. Single crystal X-ray
      diffraction study reveals that the crystal belongs to orthorhombic system with
      non centrosymmetric space group C2221. The crystalline perfection of the crystal
      was analyzed by high resolution X-ray diffraction (HRXRD) rocking curve
      measurements. Functional groups present in the crystal were analyzed
      qualitatively by infrared and Confocal Raman spectral analysis. Effects due to
      coordination of thiourea with metal ions were also discussed. Optical absorption
      study on TuAgN crystal shows the minimum absorption in the entire UV-Vis region
      and the lower cut off wavelength of TuAgN is found to be 318 nm. Thermal analysis
      shows that the material is thermally stable up to 180 degrees C. The mechanical
      strength and its parameters of the grown crystal were estimated by Vicker's
      microhardness test. The second harmonic generation (SHG) efficiency of the
      crystal was measured by Kurtz's powder technique infers that the crystal has
      nonlinear optical (NLO) efficiency 0.85 times that of KDP.

PMID- 24091347
TI  - Investigation on the adsorption characteristics of sodium benzoate and taurine on
      gold nanoparticle film by ATR-FTIR spectroscopy.
AB  - Fourier transform infrared (FTIR) spectroscopic studies of sodium benzoate and
      taurine adsorbed on gold nanoparticle (AuNp) film on silanised glass slides have
      been studied by attenuated total reflection technique (ATR). The surface
      morphology of the AuNp films has been measured by Atomic Force Microscopy. The
      ATR spectra of sodium benzoate and taurine deposited on AuNp film are compared
      with ATR spectra of their powdered bulk samples. A new red-shifted band appeared
      along with the symmetric and asymmetric stretches of carboxylate group of sodium
      benzoate leading to a broadening of the above peaks. Similar behavior is also
      seen in the case of symmetric and asymmetric stretches of sulphonate group of
      taurine. The results indicate presence of both chemisorbed and physisorbed layers
      of both sodium benzoate and taurine on the AuNp film with bottom layer chemically
      bound to AuNp through carboxylate and sulphonate groups respectively. 

PMID- 24091348
TI  - DFT study of cisplatin@carbon nanohorns complexes.
AB  - This paper reports a quantum chemical investigation of the inclusion complex
      formation between a carbon nanohorn structure and cisplatin molecule, using the
      density functional theory (DFT) with the B3LYP functional and 6-31G(d,p)/LanL2DZ
      standard basis sets. The inclusion of the drug in host molecules such as carbon
      nanohorns (CNHs), aims to reduce the toxicity and enhance the effectiveness of
      cisplatin. In this work we carried out a search for minimum energy structures on
      the potential energy surface (PES) for CNH-cisplatin interaction, and then
      calculated the stabilization energy, charge distribution and NMR spectra, which
      can be of great aid for the experimental identification of the inclusion
      compound. Our results indicate that the CNH and cisplatin can indeed form stable
      inclusion complex, with the calculated (1)H NMR and (15)N NMR chemical shifts for
      cisplatin atoms revealing very substantial changes due to complex formation
      (~20ppm) that can be easily experimentally observed, which is helpful to the
      spectra assignment and the inclusion compound structural elucidation. 

PMID- 24091349
TI  - Binding ability of glutathione towards alkyltin(IV) compounds in aqueous
      solution.
AB  - The interactions between glutathione (H3GSH) and (CH3)2Sn(2+), (CH3)3Sn(+),
      (C2H5)3Sn(+) and (C3H7)3Sn(+) cations were studied by potentiometry, UV
      spectrophotometry, (1)H NMR spectroscopy and electrospray mass spectrometry (ESI
      MS). Potentiometric measurements evidenced speciation models very similar for all
      the alkyltin(IV) cation-GSH(3-) systems, with the formation of M(GSH)(z-3),
      M(GSH)H(z-2) and M(GSH)H2(z-1) species [M(z+)=(CH3)2Sn(2+), (CH3)3Sn(+),
      (C2H5)3Sn(+), or (C3H7)3Sn(+)] and, for dimethyltin(IV) cation, also the mixed
      hydrolytic M(GSH)(OH)(2-) one. The equilibrium behavior in NaCl aqueous solution,
      at different ionic strengths and temperatures, is discussed. The stability of the
      species for the dimethyl and trialkyl cations is quite different. As an example,
      for M(GSH)(z-3), logbeta=13.33, 6.55, 6.44 and 5.84, for (CH3)2Sn(2+),
      (C3H7)3Sn(+), (C2H5)3Sn(+) and (CH3)3Sn(+), respectively (at I=0.1M and t=25
      degrees C). The speciation models and the possible structures of the complexes
      formed are discussed on the basis of spectroscopic and spectrometric results. The
      sequestering ability of glutathione towards alkyltin(IV) cations was evaluated by
      determining the concentration of the ligand able to complex half of the metal ion
      fraction (pL0.5). Glutathione shows a fairly good sequestering ability towards
      alkyltin(IV) cations, in 10(-3)-10(-5)M range. 

PMID- 24091350
TI  - Nurses' attitudes toward ethical issues in psychiatric inpatient settings.
AB  - BACKGROUND: Nursing is an occupation that deals with humans and relies upon human
      relationships. Nursing care, which is an important component of these
      relationships, involves protection, forbearance, attention, and worry.
      OBJECTIVES: The aim of this study is to evaluate the ethical beliefs of
      psychiatric nurses and ethical problems encountered. RESEARCH DESIGN: The study
      design was descriptive and cross-sectional. RESEARCH CONTEXT: Methods comprised
      of a questionnaire administered to psychiatric nurses (n=202) from five
      psychiatric hospitals in Istanbul, Turkey, instruction in psychiatric nursing
      ethics, discussion of reported ethical problems by nursing focus groups, and
      analysis of questionnaires and reports by academicians with clinical experience.
      PARTICIPANTS: PARTICIPANTS consist of the nurses who volunteered to take part in
      the study from the five psychiatric hospitals (n=202), which were selected with
      cluster sampling method. Ethical considerations: Written informed consent of each
      participant was taken prior to the study. FINDINGS: The results indicated that
      nurses needed additional education in psychiatric ethics. Insufficient personnel,
      excessive workload, working conditions, lack of supervision, and in-service
      training were identified as leading to unethical behaviors. Ethical code or
      nursing care -related problems included (a) neglect, (b) rude/careless behavior,
      (c) disrespect of patient rights and human dignity, (d) bystander apathy, (e)
      lack of proper communication, (f) stigmatization, (g) authoritarian
      attitude/intimidation, (h) physical interventions during restraint, (i)
      manipulation by reactive emotions, (j) not asking for permission, (k) disrespect
      of privacy, (l) dishonesty or lack of clarity, (m) exposure to unhealthy physical
      conditions, and (n) violation of confidence. DISCUSSION: The results indicate
      that ethical codes of nursing in psychiatric inpatient units are inadequate and
      standards of care are poor. CONCLUSION: In order to address those issues, large
      scale research needs to be conducted in psychiatric nursing with a focus on case
      studies and criteria for evaluation of service, and competency and responsibility
      needs to be established in psychiatric nursing education and practice.

PMID- 24091351
TI  - Moral distress experienced by nurses: a quantitative literature review.
AB  - Nurses are frequently confronted with ethical dilemmas in their nursing practice.
      As a consequence, nurses report experiencing moral distress. The aim of this
      review was to synthesize the available quantitative evidence in the literature on
      moral distress experienced by nurses. We appraised 19 articles published between
      January 1984 and December 2011. This review revealed that many nurses experience
      moral distress associated with difficult care situations and feel burnout, which
      can have an impact on their professional position. Further research is required
      to examine worksite strategies to support nurses in these situations and to
      develop coping strategies for dealing with moral distress. 

PMID- 24091352
TI  - Revisit of a dipropargyl rhodamine probe reveals its alternative ion sensitivity
      in both a solution and live cells.
AB  - This study reveals that a dipropargyl rhodamine B derivative previously described
      as a reaction-based irreversible palladium probe responds, however, more
      sensitively to mercury with a reversible "turn-on" fluorescence. The probe also
      shows a much better imaging ability for mercury than for palladium in live cells.

PMID- 24091353
TI  - The association between pregame snacks and exercise intensity, stress, and
      fatigue in children.
AB  - To investigate the association between pregame snacks varying in macronutrient
      content and exercise intensity, physiological stress, and fatigue in young soccer
      players. One hour before a 50-min soccer game, children (n = 79; 9.1 +/- 0.8 y)
      were randomly assigned to consume a raisin-, peanut-butter-, or cereal-based
      snack. Body mass index, blood glucose, and salivary measures of stress (cortisol
      and immunoglobulin A-IgA) were measured pre- and post-game. Exercise intensity
      was measured by accelerometry. Self-administered questionnaires were used to
      assess diet quality and fatigue. Analysis of covariance was used to examine the
      relationship between pregame snacks and biochemical outcomes. Postgame glucose
      and cortisol increased [12.9 +/- 21.3 mg/dL (p < .001) and 0.04 +/- 0.10 MUg/dL
      (p < .05), respectively] and IgA decreased (-2.3 +/- 9.6 MUg/mL; p < .001) from
      pregame values. The pregame snack was not associated with exercise intensity or
      post-game outcome; however, children consuming the cereal-based (high-sugar and
      high-glycemic index (GI)) snack exercised more intensely than the 2 lower-GI
      snack groups (p < .05). Children who consumed the high-sugar, high-GI snack also
      reported more symptoms of fatigue (p < .05). A high-sugar, high-GI pregame snack
      was associated with exercise intensity and fatigue but not changes in blood sugar
      or stress biomarkers following a soccer game in children. 

PMID- 24091354
TI  - Gemcitabine-related thrombotic microangiopathy: a single-centre retrospective
      series.
AB  - INTRODUCTION: Thrombotic microangiopathy (TMA) has been reported as a
      complication of chemotherapy. Many antineoplastic agents have been linked to TMA,
      gemcitabine being one of the most frequently cited as related to this syndrome.
      METHODS: A retrospective search for chemotherapy-induced TMA cases among
      gemcitabine users in a single oncology centre from January 2009 to September 2012
      was performed. RESULTS: Three cases of gemcitabine-induced TMA were reported,
      from a total of 264 patients (incidence: 1.13%) who received the drug. From the
      three cases reported, two (66%) patients died as a consequence of the syndrome.
      DISCUSSION: These findings are compatible with previous analyses, which report an
      incidence of gemcitabine-associated TMA ranging from 0.008 to 2.2% and mortality
      rates from 15 to 90%. Unlike previously reported, however, cumulative dose was
      not predictive of risk. CONCLUSION: Gemcitabine-induced TMA is an underdiagnosed
      condition characterized by high mortality rates. Attention should be called for a
      higher level of awareness to provide early diagnosis and proper treatment.

PMID- 24091355
TI  - Ag/GeSx/Pt-based complementary resistive switches for hybrid CMOS/nanoelectronic
      logic and memory architectures.
AB  - Complementary resistive switches based on two anti-serially connected Ag/GeSx/Pt
      devices were studied. The main focus was placed on the pulse mode properties as
      typically required in memory and logic applications. A self-designed measurement
      setup was applied to access each CRS part-cell individually. Our findings reveal
      the existence of two distinct read voltage regimes enabling both spike read as
      well as level read approaches. Furthermore, we experimentally verified the
      theoretically predicted kinetic properties in terms of pulse height vs. switching
      time relationship. The results obtained by this alternative approach allow a
      significant improvement of the basic understanding of the interplay between the
      two part-cells in a complementary resistive switch configuration. Furthermore,
      from these observations we can deduce a simplified write voltage scheme which is
      applicable for the considered type of memory cell. 

PMID- 24091356
TI  - Cholesterol ester transfer protein (CETP) gene polymorphism and selected
      parameters of lipid metabolism in children from families with history of
      cardiovascular system diseases.
AB  - BACKGROUND: Children from families with a history of cardiovascular system
      diseases are especially predisposed to early development of atherosclerosis.
      Therefore, the aim of this study was to examine the selected lipid parameters and
      polymorphisms of G279A located in the cholesterol ester transfer protein (CETP)
      gene. MATERIAL/METHODS: This longitudinal study was performed in 3 stages. During
      stage I the tests were carried out on 137 newborns after birth. Of these, we
      selected 30 children with a family history of cardiovascular system diseases.
      During stage II of the study the same children were evaluated at the age of 18-30
      months, and during stage III at the age 5-6 years. Gestational age and the birth
      weight were evaluated in newborns. The older children were examined physically,
      and nutritional status was assessed. In all of the children examined, we
      determined the blood concentrations of triglycerides, total cholesterol, high
      density lipoprotein (HDL) cholesterol, apolipoproteins (AI and B), lipoprotein(a)
      and polymorphisms, and the G279A locus of the CETP gene. RESULTS: In children
      with genotype B1B1 (after birth and aged 5-6 years), a significantly lower
      cholesterol concentration in the HDL fraction was found compared to those with
      genotype B1B2 and B2B2. Other biochemical parameters of lipid metabolism were not
      significantly different between these genetic polymorphisms. CONCLUSIONS: A lower
      cholesterol concentration in the HDL fraction in children with a family history
      of cardiovascular system diseases was determined by polymorphism of the CETP
      gene. Homozygotes (genotype B1B1) show a tendency towards the phenotype favoring
      the development of atherosclerosis.

PMID- 24091357
TI  - Effect of iodinated contrast media on renal function evaluated with dynamic three
      dimensional MR renography.
AB  - PURPOSE: To assess the hemodynamic effect of iodinated contrast media (CM) on
      glomerular filtration rate (GFR) by using dynamic three-dimensional magnetic
      resonance (MR) renography in a rabbit model. MATERIALS AND METHODS: This study
      was approved by the university animal care and use committee. Twelve healthy male
      New Zealand rabbits (body mass range, 2.5-3.0 kg) were included. Two of them were
      sacrificed before MR examination to obtain renal histologic samples as controls.
      The other ten rabbits completed 4-minute dynamic contrast material-enhanced MR
      imaging 24 hours before and 20 minutes after intravenous injection of iopamidol
      (370 mg of iodine per milliliter) at a dose of 6 mL per kilogram of body weight.
      Blood volume (V(B)), GFR, and tubule volume (V(E)) of the renal cortex were
      determined with a two-compartment kinetic model. Maximum upslope (K(m)), peak
      concentration (P(c)), and initial 60-second area under the curve (IAUC) of the
      whole kidney renogram curve were measured with semiquantitative analysis. The
      self-control data were compared by using the Student paired t test. RESULTS:
      Iopamidol significantly decreased cortical V(B) (mean, 42.53% +/- 10.16 [standard
      deviation] before CM administration vs 27.23% +/- 16.13 after CM administration;
      P < .01), V(E) (mean, 22.40% +/- 11.69 before CM administration vs 11.51% +/-
      6.58 after CM administration; P < .01), and GFR (mean, 31.92 mL/100 g per minute
      +/- 12.52 before CM administration vs 21.48 mL/100 g per minute +/- 10.02 after
      CM administration; P < .01). Results of whole-kidney renogram analysis showed a
      decrease in K(m), P(c), and IAUC caused by iopamidol administration. CONCLUSION:
      High-dose iopamidol resulted in a marked decrease in renal function, which could
      be detected at dynamic three-dimensional MR renography.

PMID- 24091358
TI  - Nonalcoholic fatty liver disease: intravoxel incoherent motion diffusion-weighted
      MR imaging-an experimental study in a rabbit model.
AB  - PURPOSE: To evaluate the feasibility of using intravoxel incoherent motion (IVIM)
      diffusion-weighted imaging with multiple b values for the noninvasive diagnosis
      of nonalcoholic fatty liver disease (NAFLD). MATERIALS AND METHODS: This study
      was approved by the institutional animal care and use committee. Twenty-seven 8
      week-old rabbits were fed a variety of diets (from a standard diet to a high-fat,
      high-cholesterol diet) before IVIM diffusion-weighted imaging was performed with
      seven b values by using a 3-T magnetic resonance (MR) imaging unit. At histologic
      analysis of the animals, livers were categorized by NAFLD severity as normal,
      NAFLD, borderline nonalcoholic steatohepatitis (NASH), or NASH. The apparent
      diffusion coefficient and IVIM-derived parameters including true diffusion
      coefficient, pseudodiffusion coefficient, and perfusion fraction of the liver
      parenchyma were measured. Each parameter was correlated with NAFLD severity, and
      optimal cutoff values were determined by means of receiver operating
      characteristics analysis. RESULTS: Perfusion fraction was significantly lower in
      rabbits with NAFLD than in those with a normal liver, and it decreased further as
      severity of NAFLD increased, with medians of 22.2%, 14.8%, 11.3%, and 9.5% in the
      rabbits in the normal, NAFLD, borderline, and NASH groups, respectively (rho = 
      0.83, P < .001). Apparent diffusion coefficient, true diffusion coefficient, and
      pseudodiffusion coefficient were not significantly different between the NAFLD
      severity groups. In terms of the diagnostic performance of perfusion fraction,
      area under the curve values were 0.984 (normal vs NAFLD or more severe disease),
      0.959 (NAFLD or less severe vs borderline or more severe disease), and 0.903
      (borderline or less severe vs NASH) with optimal cutoff values of 15.2%, 13.2%,
      and 11.0%, respectively. CONCLUSION: Perfusion fractions extracted from IVIM
      diffusion-weighted imaging may help in the differentiation of early stage NASH
      from simple steatosis.

PMID- 24091359
TI  - Model-based iterative reconstruction: effect on patient radiation dose and image
      quality in pediatric body CT.
AB  - PURPOSE: To retrospectively compare image quality and radiation dose between a
      reduced-dose computed tomographic (CT) protocol that uses model-based iterative
      reconstruction (MBIR) and a standard-dose CT protocol that uses 30% adaptive
      statistical iterative reconstruction (ASIR) with filtered back projection.
      MATERIALS AND METHODS: Institutional review board approval was obtained. Clinical
      CT images of the chest, abdomen, and pelvis obtained with a reduced-dose protocol
      were identified. Images were reconstructed with two algorithms: MBIR and 100%
      ASIR. All subjects had undergone standard-dose CT within the prior year, and the
      images were reconstructed with 30% ASIR. Reduced- and standard-dose images were
      evaluated objectively and subjectively. Reduced-dose images were evaluated for
      lesion detectability. Spatial resolution was assessed in a phantom. Radiation
      dose was estimated by using volumetric CT dose index (CTDI(vol)) and calculated
      size-specific dose estimates (SSDE). A combination of descriptive statistics,
      analysis of variance, and t tests was used for statistical analysis. RESULTS: In
      the 25 patients who underwent the reduced-dose protocol, mean decrease in
      CTDI(vol) was 46% (range, 19%-65%) and mean decrease in SSDE was 44% (range, 19%
      64%). Reduced-dose MBIR images had less noise (P > .004). Spatial resolution was
      superior for reduced-dose MBIR images. Reduced-dose MBIR images were equivalent
      to standard-dose images for lungs and soft tissues (P > .05) but were inferior
      for bones (P = .004). Reduced-dose 100% ASIR images were inferior for soft
      tissues (P < .002), lungs (P < .001), and bones (P < .001). By using the same
      reduced-dose acquisition, lesion detectability was better (38% [32 of 84 rated
      lesions]) or the same (62% [52 of 84 rated lesions]) with MBIR as compared with
      100% ASIR. CONCLUSION: CT performed with a reduced-dose protocol and MBIR is
      feasible in the pediatric population, and it maintains diagnostic quality.

PMID- 24091360
TI  - Hypoglycemia as a manifestation of iatrogenic adrenal insufficiency due to
      topical steroids.

PMID- 24091361
TI  - Analysis of small RNAs derived from tomato yellow leaf curl Sardinia virus
      reveals a cross reaction between the major viral hotspot and the plant host
      genome.
AB  - RNA silencing is a defense mechanism exploited by plants against viruses. Upon
      infection, viral genomes and their transcripts are processed by Dicer-like (DCL)
      ribonucleases into viral small interfering RNAs (vsRNAs) of 21-24 nucleotides
      that further guide silencing of viral transcripts. To get an insight into the
      molecular interaction between tomato and the monopartite phloem-limited
      begomovirus tomato yellow leaf curl Sardinia virus (TYLCSV), a pathogen inducing
      a devastating disease of tomato in the Mediterranean region, we characterized by
      deep sequencing the vsRNA population in virus-infected tomato plants, using a
      Solexa/Illumina platform. TYLCSV-sRNAs spanned the entire viral genome but were
      discontinuously distributed throughout it, with a prevalence from the transcribed
      regions. TYLCSV-sRNAs were mainly 21-22 nucleotides in length and their polarity
      was asymmetrically distributed along the genome. The most abundant vsRNAs
      originated from a narrow region overlapping the Rep/C4 genes and from a broader
      region including the end of the V2 and the beginning of the coat protein genes.
      Deep sequencing results were validated by different hybridization techniques.
      Comparisons with the data available on vsRNAs for other begomoviruses highlighted
      both similarities and differences. Host-derived RNA species cross-reacting with a
      portion of the viral genome corresponding to the most abundant vsRNAs hotspot
      were detected. Bioinformatics analyses were carried out to investigate the nature
      of these host molecules. 

PMID- 24091362
TI  - The evolution of codon usage in structural and non-structural viral genes: the
      case of Avian coronavirus and its natural host Gallus gallus.
AB  - To assess the codon evolution in virus-host systems, Avian coronavirus and its
      natural host Gallus gallus were used as a model. Codon usage (CU) was measured
      for the viral spike (S), nucleocapsid (N), nonstructural protein 2 (NSP2) and
      papain-like protease (PL(pro)) genes from a diverse set of A. coronavirus
      lineages and for G. gallus genes (lung surfactant protein A, intestinal
      cholecystokinin, oviduct ovomucin alpha subunit, kidney vitamin D receptor and
      the ubiquitary beta-actin) for different A. coronavirus replicating sites.
      Relative synonymous codon usage (RSCU) trees accommodating all virus and host
      genes in a single topology showed a higher proximity of A. coronavirus CU to the
      respiratory tract for all genes. The codon adaptation index (CAI) showed a lower
      adaptation of S to G. gallus compared to NSP2, PL(pro) and N. The effective
      number of codons (Nc) and GC3% revealed that natural selection and genetic drift
      are the evolutionary forces driving the codon usage evolution of both A.
      coronavirus and G. gallus regardless of the gene being considered. The spike gene
      showed only one 100% conserved amino acid position coded by an A. coronavirus
      preferred codon, a significantly low number when compared to the three other
      genes (p<0.0001). Virus CU evolves independently for each gene in a manner
      predicted by the protein function, with a balance between natural selection and
      mutation pressure, giving further molecular basis for the viruses' ability to
      exploit the host's cellular environment in a concerted virus-host molecular
      evolution. 

PMID- 24091363
TI  - Nonstructural proteins of Torque teno sus virus 2 from O2AUG: prediction to
      experimental validation.
AB  - The expression profiles of nonstructural proteins (NSPs) in Torque teno sus virus
      2 (TTSuV2) have not yet been characterized. Here, we determined the coding
      sequences of the TTSuV2 NSPs ORF2, ORF2/2, and ORF2/2/3 by overlapping polymerase
      chain reaction (PCR) and subsequent expression in bacterial and mammalian cells.
      We generated two monoclonal antibodies (mAbs), 2E5 and 6F8, from mice immunized
      with mixed Escherichia coli expressing His-tagged ORF2 and ORF2/2. Enzyme-linked
      immunosorbent assay (ELISA) and western blot analysis revealed that, 2E5 mAbs
      bound to the consensus sequences of ORF2, ORF2/2, and ORF2/2/3, while 6F8
      recognized the common sequences of ORF2/2 and ORF2/2/3. Immunofluorescence assay
      (IFA) revealed that ORF2 was localized in the cytoplasm, ORF2/2, in the nucleus
      but not the nucleolus, and ORF2/2/3, in the peri-nuclear region. To identify the
      expression profiles of TTSuV NSPs, a circular TTSuV2_ZJ (GenBank: KF660540)
      genomic DNA clone was constructed and transfected into HEK293T and HeLa cells.
      Splicing mRNAs and the expression and localization of ORF2/2 and ORF2/2/3 were
      identified by RT-PCR, western blot analysis, and IFA, respectively. However, ORF2
      was not detected either at the RNA or protein level. Our study is the first to
      provide experimental evidence of the existence of ORF2/2 and ORF2/2/3 at the
      protein level. Moreover, the mAbs have potential applications in future research
      on TTSuV2 viral protein function and diagnosis of related diseases. 

PMID- 24091364
TI  - Nine novel DNA components associated with the foorkey disease of large cardamom:
      evidence of a distinct babuvirus species in Nanoviridae.
AB  - Foorkey disease is a serious constraint to the production of large cardamom
      (Amomum subulatum, family Zingiberaceae). The disease is characterized by profuse
      proliferation of excessive stunted shoots, which makes the clump totally
      unproductive. The disease has been known in India since 1936 but the complete
      genome of the virus had not yet been characterized. In a preliminary study, an
      associated virus tentatively named as Cardamom bushy dwarf virus (CBDV) was
      identified based on the partial sequence of a single DNA component (DNA-R). In
      the present study, a high incidence (37.2-39.3%) of foorkey was recorded in
      certain plantations in the Darjeeling hills located at lower altitudes (300-1380
      m) and CBDV was detected in several field samples by PCR. Nine novel DNA
      components were isolated and characterized from foorkey affected plants. CBDV
      contained six major DNA components (DNA-R, -S, -M, -C, -N and -U3) similar to the
      integral genome components known for the members of the genus Babuvirus in the
      family Nanoviridae. Additional components, satellite Rep (DNA-sRep1) and unknown
      components (DNA-Uf1 and -Uf2) were also identified. The size of the genome
      components ranged from 1028 to 1127. The sequence identity and phylogeny based on
      the individual components as well as overall genome (59.8-62% identity)
      distinguished CBDV from the two existing babuvirus species, Banana bunchy top
      virus and Abaca bunchy top virus. CBDV is the first distinct babuvirus species
      that affects plant species outside family Musaceae. This study shows further
      diversity in the genus Babuvirus.

PMID- 24091365
TI  - Detection of porcine anelloviruses in pork meat and human faeces.
AB  - Torque teno viruses (TTV) are icosahedral, single-stranded circular DNA viruses
      infecting several vertebrate species. Currently, these viruses are considered non
      pathogenic although they are suggested to be co-factors in several diseases.
      Recently single-stranded circular DNA viruses have been found in human faeces.
      Considering the consumption of pork meat products and the ubiquitous nature of
      swine TTV (Torque tenosus virus, TTSuV), the human population is frequently
      exposed to these viruses. To determine if TTSuVs could be delivered through food,
      human faecal samples were analysed for their presence. Indeed, the results of
      this study show that up to 25% of faecal samples were positive for known TTSuVs
      by PCR and sequencing. Additionally, all commercially available pork products
      purchased in Spanish supermarkets contained DNA of TTSuV. 

PMID- 24091367
TI  - Prenatal exposure to bisphenol A interferes with the development of cerebellar
      granule neurons in mice and chicken.
AB  - In mice, prenatal exposure to low doses of bisphenol A has been shown to affect
      neurogenesis and neuronal migration in cortex, resulting in disturbance of both
      neuronal positioning and the network formation between thalamus and cortex in the
      offspring brain. In the present study we investigated whether prenatal exposure
      to bisphenol A disturbs the neurodevelopment of the cerebellum. Two different
      model systems were used; offspring from two strains of mice from mothers
      receiving bisphenol A in the drinking water before mating, during gestation and
      lactation, and chicken embryos exposed to bisphenol A (in the egg) on embryonic
      day 16 for 24h before preparation of cerebellar granule cell cultures. In the
      cerebellum, tight regulation of the level of transcription factor Pax6 is
      critical for correct development of granule neurons. During the development, the
      Pax6 level in granule neurons is high when these cells are located in the
      external granule layer and during their migration to the internal granule layer,
      and it is then reduced. We report that bisphenol A induced an increase in the
      thickness of the external granule layer and also an increase in the total
      cerebellar Pax6 level in 11 days old mice offspring. In cultured chicken
      cerebellar granule neurons from bisphenol A injected eggs the Pax6 level was
      increased day 6 in vitro. Together, these findings indicate that bisphenol A may
      affect the granule neurons in the developing cerebellum and thereby may disturb
      the correct development of the cerebellum. 

PMID- 24091366
TI  - Further characterisation of rotavirus cores: Ss(+)RNAs can be packaged in vitro
      but packaging lacks sequence specificity.
AB  - Rotavirus (RV) cores were released from double-layered particles (DLPs) by high
      concentrations of CaCl2, purified and 'opened' by treatment with EDTA or EGTA.
      Under appropriate in vitro conditions DLPs have been shown to have transcriptase
      and 'open cores' replicase activity. Furthermore, it has been demonstrated that
      transcriptase activity and infectivity of native cores can be restored by
      transcapsidation with VP6, VP7 and VP4. The missing link for particle
      reconstitution in vitro has been the manipulation of 'open cores' to become
      functionally active cores again. The experiments described here were undertaken
      with the aim of exploring packaging of RV RNAs into opened cores in vitro.
      Rotavirus cores were opened by approximately 200MUM EGTA, leading to the release
      of genomic dsRNA. Conversely, RV cores were found to be stable in the presence of
      minimum concentrations of Ca(2+), Mg(2+), spermidine(3+) and cobalthexamine(3+)
      of between 40 and 300 MUM. Aggregates of purified cores were resolved in the
      presence of 0.3mM deoxycholate (minimum concentration). Core shells opened with
      EGTA were reconstituted by the addition of di- or trivalent cations within 2 min
      of the opening procedure. Addition of purified, baculovirus recombinant-expressed
      VP6 to native and reconstituted cores led to the formation of DLPs or DLP-like
      particles, which upon transfection into MA104 cells were infectious. The rescued
      infectivity likely originated in part from unopened and in part from
      reconstituted cores. Radiolabelled RV (+) ssRNAs could be packaged into
      reconstituted cores and DLPs, as indicated by resistance to RNase I digestion.
      The packaging reaction was, however, not RV RNA sequence-specific, since
      unrelated ssRNAs, such as those transcribed from HIV-2 cDNAs, were also packaged.
      The kinetics of packaging of homologous and heterologous RNAs were similar, as
      evidenced by competitive packaging assays. None of the packaged in vitro
      engineered RNA segments has so far been rescued into infectious virus.

PMID- 24091368
TI  - Comparison of copper labeling followed by liquid chromatography-inductively
      coupled plasma mass spectrometry and immunochemical assays for serum hepcidin-25
      determination.
AB  - Hepcidin-25 has been defined as the key biomarker in iron metabolism. This
      peptide binds to the iron transporter ferroportin to cause its degradation.
      Therefore, the need for specific, accurate and precise methods for the
      quantification of hepcidin-25 in biological fluids is dramatically increasing. In
      this regard, the use of rapid immunochemical methods that provide low limit of
      quantification is desired for routine clinical use. However, such fast
      methodologies should be first analytically evaluated and compared with
      alternative strategies to check for their advantages and limitations. Here we
      compare the use of a commercial immunochemical assay for hepcidin determination
      with a novel analytical approach based on Cu-labeling of the peptide followed by
      Cu determination using liquid chromatography (HPLC) and plasma mass spectrometry
      (ICP-MS). The figures of merit of both systems reveal similar analytical
      characteristics and both seem to be adequate for the determination of the peptide
      at biologically relevant concentrations in human serum samples. The analysis of a
      larger number of samples (n=50) by both techniques showed a good agreement in the
      concentrations found. Such finding permits to address the hepcidin recovery in
      the sample preparation procedure necessary for the HPLC-ICP-MS analysis in human
      serum that turn out to be 76-85%. Additionally, limitations due to cross
      reactivity issues of the ELISA method could be addressed in some of the samples
      by using LC-ICP-MS and were confirmed by LC-Electrospray-MS. 

PMID- 24091369
TI  - Microextraction techniques for the determination of volatile and semivolatile
      organic compounds from plants: a review.
AB  - Vegetables and fruits are necessary for human health, and traditional Chinese
      medicine that uses plant materials can cure diseases. Thus, understanding the
      composition of plant matrix has gained increased attention in recent years. Since
      plant matrix is very complex, the extraction, separation and quantitation of
      these chemicals are challenging. In this review we focus on the microextraction
      techniques used in the determination of volatile and semivolatile organic
      compounds (such as esters, alcohols, aldehydes, hydrocarbons, ketones, terpenes,
      sesquiterpene, phenols, acids, plant secondary metabolites and pesticides) from
      plants (e.g., fruits, vegetables, medicinal plants, tree leaves, etc.). These
      microextraction techniques include: solid phase microextraction (SPME), stir-bar
      sorptive extraction (SBSE), single drop microextraction (SDME), hollow fiber
      liquid phase microextraction (HF-LPME), dispersive liquid liquid microextraction
      (DLLME), and gas purge microsyringe extraction (GP-MSE). We have taken into
      consideration papers published from 2008 to the end of January 2013, and provided
      critical and interpretative review on these techniques, and formulated future
      trends in microextraction for the determination of volatile and semivolatile
      compounds from plants. 

PMID- 24091370
TI  - Determination of in situ speciation of manganese in treated acid mine drainage
      water by using multiple diffusive gradients in thin films devices.
AB  - Acid mine drainage (AMD) is a serious environmental problem that creates acidic
      solution with high Mn concentrations. The speciation of residual Mn from AMD
      after an active treatment involving the addition of a neutralizing agent can
      reliably evaluate the treatment efficiency and provide knowledge of the Mn
      species being inputted into the environment. The aim of this study was to
      evaluate the in situ lability and speciation of Mn using the diffusive gradients
      in thin films (DGT) technique with treated drainage water from a uranium mine
      (TAMD). DGT devices with different binding phases (Chelex-100 and P81 and DE81
      membranes) were used to perform the in situ speciation of Mn. A comparison of the
      results from deploying DGT in the laboratory and in situ shows that the
      speciation of Mn in TAMD should be performed in situ. Linear deployment curves
      (from in situ experiments) indicate that the DGT device containing the Chelex-100
      binding phase can be used to evaluate Mn lability in TAMD. The labile Mn fraction
      (from in situ measurements) obtained using the device containing the Chelex-100
      resin ranged from 63 to 81% of the total Mn concentration and, when compared to
      the speciation obtained using the CHEAQS software, indicated that this device was
      capable of uptaking the free Mn(2+) and a portion of the MnSO4(aq). The values
      obtained using the DGT technique were compared to those from on site solid phase
      extraction, and a good agreement was found between the results. The amount of
      negative Mn species sampled by DE81 device was insignificant (<1.5%) for all of
      the sites. Sites containing a relatively small amount of Ca (<40 mg L(-1)) and
      measured using devices containing the P81 membrane agreed with the concentration
      predicted by the CHEAQS software for positive Mn species (Mn(2+) and Mn(OH)(+)).
      Nevertheless, the speciation obtained using the CHEAQS software indicated that
      the concentrations of positive Mn species were underestimated for sites with
      relatively high Ca concentrations (>150 mg L(-1)), which take place due to the
      saturation of binding sites in the P81 membrane.

PMID- 24091371
TI  - A new method for the automated selection of the number of components for
      deconvolving overlapping chromatographic peaks.
AB  - Mathematical deconvolution methods can separate co-eluting peaks in samples for
      which (chromatographic) separation fail. However, these methods often heavily
      rely on manual user-input and interpretation. This is not only time-consuming but
      also error-prone and automation is needed if such methods are to be applied in a
      routine manner. One major hurdle when automating deconvolution methods is the
      selection of the correct number of components used for building the model. We
      propose a new method for the automatic determination of the optimum number of
      components when applying multivariate curve resolution (MCR) to comprehensive two
      dimensional gas chromatography-mass spectrometry (GC*GC-MS) data. It is based on
      a two-fold cross-validation scheme. The obtained overall cross-validation error
      decreases when adding components and increases again once over-fitting of the
      data starts to occur. The turning point indicates that the optimum number of
      components has been reached. Overall, the method is at least as good as and
      sometimes superior to the inspection of the eigenvalues when performing singular
      value decomposition. However, its strong point is that it can be fully automated
      and it is thus more efficient and less prone to subjective interpretation. The
      developed method has been applied to two different-sized regions in a GC*GC-MS
      chromatogram. In both regions, the cross-validation scheme resulted in selecting
      the correct number of components for applying MCR. The pure concentration and
      mass spectral profiles obtained can then be used for identification and/or
      quantification of the compounds. While the method has been developed for applying
      MCR to GC*GC-MS data, a transfer to other deconvolution methods and other
      analytical systems should only require minor modifications. 

PMID- 24091372
TI  - Signal-on impedimetric electrochemical DNA sensor using dithiothreitol modified
      gold nanoparticle tag for highly sensitive DNA detection.
AB  - A signal-on impedimetric electrochemical DNA (E-DNA) sensor using gold
      nanoparticles (AuNPs) as tag was developed for highly sensitive detection of DNA
      hybridization. A probe ssDNA (PDNA) was immobilized by forming an amide between
      the -NH2 moiety at the 5'-terminus of PDNA and the -COOH group at self-assembled
      11-mercaptoundecanoic acid on a gold electrode. Subsequently, AuNPs were attached
      to the -SH moiety at the 3'-terminus of the immobilized PDNA by S-Au interaction,
      and then functionalized with -OH by immersing the electrode in dithiothreitol
      solution. In the absence of the target DNA, the flexible single-stranded PDNA
      supports efficient contact between AuNP tag and electrode, ensuring a low
      electron transfer resistance (Ret) of the E-DNA sensor using the [Fe(CN)6](3-/4-)
      redox probe. Upon hybridization, a rigid probe-target duplex is formed, which
      pushes the AuNP tag away from the electrode and increases the distance between
      AuNP tag and the electrode, thereby increasing the Ret of the E-DNA sensor. Based
      on hybridization-induced conformational changes, the E-DNA sensor shows an
      increased Ret response when the target DNA concentration is increased from 5 fM
      to 500 pM. Furthermore, the E-DNA sensor showed differentiation abilities for
      single-base mismatch.

PMID- 24091373
TI  - Molecule-binding dependent assembly of split aptamer and gamma-cyclodextrin: a
      sensitive excimer signaling approach for aptamer biosensors.
AB  - A highly sensitive and selective fluorescence aptamer biosensors for the
      determination of adenosine triphosphate (ATP) was developed. Binding of a target
      with splitting aptamers labeled with pyrene molecules form stable pyrene dimer in
      the gamma-cyclodextrin (gamma-CD) cavity, yielding a strong excimer emission. We
      have found that inclusion of pyrene dimer in gamma-cyclodextrin cavity not only
      exhibits additive increases in quantum yield and emission lifetime of the
      excimer, but also facilitates target-induced fusion of the splitting aptamers to
      form the aptamer/target complex. As proof-of-principle, the approach was applied
      to fluorescence detection of adenosine triphosphate. With an anti-ATP aptamer,
      the approach exhibits excimer fluorescence response toward ATP with a maximum
      signal-to-background ratio of 32.1 and remarkably low detection limit of 80 nM
      ATP in buffer solution. Moreover, due to the additive fluorescence lifetime of
      excimer induced by gamma-cyclodextrin, time-resolved measurements could be
      conveniently used to detect as low as 0.5 MUM ATP in blood serum quantitatively.

PMID- 24091374
TI  - Fluorescence quenching studies on the interaction of a novel deepened cavitand
      towards some transition metal ions.
AB  - A novel 'three-level' deepened cavitand featuring a significantly sizable portal
      has been synthesized and its interaction with some transition metal ions has been
      investigated in THF/H2O binary solvent using fluorescence quenching technique.
      The results suggest that among the used transition metal ions including Ag(+),
      Cd(2+), Cu(2+), Fe(3+), Cr(3+), Hg(2+), La(3+), Mn(2+), Ni(2+), Zn(2+) and
      Co(2+), only Fe(3+) and Cu(2+) show good quenching ability. In order to interpret
      the quenching mechanism, the Stern-Volmer kinetics, and the presence of both the
      dynamic and static quenching have been discussed. It was found that the
      simultaneous presence of the sphere-of-action static quenching and dynamic
      quenching model agrees very well with the experimental results. The limits of
      detection for Fe(3+) and Cu(2+) were found to be 2.1*10(-6) mol L(-1) (3sigma)
      and 3.6*10(-6) mol L(-1) (3sigma), respectively. Cations with potential
      interference, such as K(+), Na(+), Mg(2+), Ca(2+), Co(2+), La(3+) and Mn(2+) do
      not have significant effects on the determinations of Fe(3+) and Cu(2+). This
      cavitand can be potentially applied as optical sensor for the detection of Fe(3+)
      and Cu(2+).

PMID- 24091375
TI  - Ion exchange liquid chromatography method for the direct determination of small
      ribonucleic acids.
AB  - Bioanalysis of siRNAs is challenging due to their size (5-14 kDa) and negative
      charge across the backbone, which complicates both sample preparation and
      chromatography. We present here a one step sample preparation combined with non
      denaturing anion exchange chromatography with UV detection for the quantitation
      of siRNA and its chain shortened metabolites. The sample preparation uses a novel
      lysis buffer with proteinase K to effectively isolate siRNA from cells and
      formulated media with greater than 95% recovery. The ion exchange chromatography
      allows for a lower limit of quantitation of 6 ng mL(-1) in cells and media
      equivalent to 6 ng/200,000 cells. This method is applied to study the uptake of
      siRNA in prostate cancer cells and the disappearance in the media and siRNA
      metabolism. siRNA metabolites are identified by matching the retention time of
      standards to metabolite peaks. Identification is further confirmed by mass
      spectrometry. To our knowledge this is the first ion exchange method reported for
      the quantitation of siRNA from a biological matrix. It is also the first non
      denaturing chromatographic method reported for siRNA quantitation.

PMID- 24091376
TI  - Development of a sensitive and reliable high performance liquid chromatography
      method with fluorescence detection for high-throughput analysis of multi-class
      mycotoxins in Coix seed.
AB  - As an edible and medicinal plant, Coix seed is readily contaminated by more than
      one group of mycotoxins resulting in potential risk to human health. A reliable
      and sensitive method has been developed to determine seven mycotoxins (aflatoxins
      B1, B2, G1, G2, zearalenone, alpha-zearalenol, and beta-zearalenol)
      simultaneously in 10 batches of Coix seed marketed in China. The method is based
      on a rapid ultrasound-assisted solid-liquid extraction (USLE) using
      methanol/water (80/20) followed by immunoaffinity column (IAC) clean-up, on-line
      photochemical derivatization (PCD), and high performance liquid chromatography
      coupled with fluorescence detection (HPLC-FLD). Careful optimization of
      extraction, clean-up, separation and detection conditions was accomplished to
      increase sample throughput and to attain rapid separation and sensitive
      detection. Method validation was performed by analyzing samples spiked at three
      different concentrations for the seven mycotoxins. Recoveries were from 73.5% to
      107.3%, with relative standard deviations (RSDs) lower than 7.7%. The intra- and
      inter-day precisions, expressed as RSDs, were lower than 4% for all studied
      analytes. Limits of detection and quantification ranged from 0.01 to 50.2 MUg kg(
      1), and from 0.04 to 125.5 MUg kg(-1), respectively, which were below the
      tolerance levels for mycotoxins set by the European Union. Samples that tested
      positive were further analyzed by HPLC tandem electrospray ionization mass
      spectrometry for confirmatory purposes. This is the first application of USLE-IAC
      HPLC-PCD-FLD for detecting the occurrence of multi-class mycotoxins in Coix seed.

PMID- 24091377
TI  - Development, optimization and application of an analytical methodology by ultra
      performance liquid chromatography-tandem mass spectrometry for determination of
      amanitins in urine and liver samples.
AB  - Amanitins, highly toxic cyclopeptides isolated from various Amanita species, are
      the most potent poisons accounting for the hazardous effects on intestinal
      epithelium cells and hepatocytes, and probably the sole cause of fatal human
      poisoning. The present study was focused on the development, optimization and
      application of an analytical methodology by ultra performance liquid
      chromatography-tandem mass spectrometry (UPLC-MS/MS), following urine and liver
      sample preparation by protein precipitation with organic solvents, and solid
      phase extraction (SPE) procedure, for the determination of the amatoxins, alpha-
      and beta-amanitin. Linearity, detection and quantification limits, selectivity,
      sensitivity, intra and inter-assay precision and recovery were studied, in order
      to guarantee reliability in the analytical results. The developed method proved
      to be specific and selective, with LOD (Limit of Detection) values for alpha- and
      beta-amanitin of 0.22 and 0.20 ng mL(-1) in urine and 10.9 and 9.7 ng g(-1) in
      liver, respectively. LOQ (Limit of Quantification) values ranged from 0.46 to
      0.57 ng mL(-1) in urine and 12.3-14.7 ng g(-1) in tissue, for both amanitins.
      Linearity, in the range of 10.0-200.0 ng mL(-1) or ng g(-1), shows that
      coefficients of correlation were greater than 0.997 for alpha-amanitin and 0.993
      for beta-amanitin. Precision was checked at three levels during three consecutive
      days with intra-day and inter-day coefficients of variation not greater than
      15.2%. The extraction recovery presents good results for the concentrations
      analyzed, with values ranging from 90.2 to 112.9% for both matrices. Thus, the
      proposed analytical method is innovative, presents a high potential in the
      identification, detection and determination of alpha- and beta-amanitins in urine
      and tissue samples, as well as in other biological samples, such as kidney and
      mushrooms.

PMID- 24091378
TI  - Separation of polychlorinated dibenzo-p-dioxins/furans, non
      ortho/mono/di/tri/tetra-ortho-polychlorinated biphenyls, and polybrominated
      diphenyl ethers groups of compounds prior to their determination with large
      volume injection gas chromatography-Quadrupole ion storage tandem mass
      spectrometry.
AB  - Polychlorinated dibenzo-p-dioxins/furans (PCDD/Fs), polychlorinated biphenyls
      (PCBs) and polybrominated diphenyl ethers (PBDEs) are important environmental
      contaminants. Their maximum legally allowable levels in food and environment are
      in the low pg g(-1) range. Therefore some highly selective and sensitive
      analytical methods must be used to determine them. Prior to final determination
      by GC/MS the cleaned-up samples have to be split into some fractions in view of
      large differences in concentrations of various analytes and existence of numerous
      chromatographic co-elutions (which in any case cannot be fully avoided). The aim
      of this study was to: (i) develop a robust, time-saving analytical method to
      isolate, clean-up and fractionate PCBs, PBDEs and PCDD/Fs prior to their
      determination with gas chromatography/ion trap mass spectrometry; (ii) assess
      method performance using laboratory validation data and some certified reference
      materials; (iii) use the developed method to assess PCB/PBDE/PCDD/F levels in
      samples of commercially available food. A combination of alumina, florisil,
      modified silica gel and two carbon columns were used for sample cleanup and
      fractionation. Separate fractions containing dioxins/furans, PBDE, non-ortho,
      mono-ortho and di-/tri-/tetra-ortho PCBs were obtained. The method statistical
      parameters were compatible with 1883/2006 EC Regulation (80-120%, RSD below 15%).
      The method performance was successfully used to evaluation of some real life food
      samples.

PMID- 24091379
TI  - Growth of carbon nanotubes via twisted graphene nanoribbons.
AB  - Carbon nanotubes have long been described as rolled-up graphene sheets. It is
      only fairly recently observed that longitudinal cleavage of carbon nanotubes,
      using chemical, catalytical and electrical approaches, unzips them into thin
      graphene strips of various widths, the so-called graphene nanoribbons. In
      contrast, rolling up these flimsy ribbons into tubes in a real experiment has not
      been possible. Theoretical studies conducted by Kit et al. recently demonstrated
      the tube formation through twisting of graphene nanoribbon, an idea very
      different from the rolling-up postulation. Here we report the first experimental
      evidence of a thermally induced self-intertwining of graphene nanoribbons for the
      preferential synthesis of (7, 2) and (8, 1) tubes within parent-tube templates.
      Through the tailoring of ribbon's width and edge, the present finding adds a
      radically new aspect to the understanding of carbon nanotube formation, shedding
      much light on not only the future chirality tuning, but also contemporary
      nanomaterials engineering. 

PMID- 24091380
TI  - Can anonymous posters on medical forums be reidentified?
AB  - BACKGROUND: Participants in medical forums often reveal personal health
      information about themselves in their online postings. To feel comfortable
      revealing sensitive personal health information, some participants may hide their
      identity by posting anonymously. They can do this by using fake identities,
      nicknames, or pseudonyms that cannot readily be traced back to them. However,
      individual writing styles have unique features and it may be possible to
      determine the true identity of an anonymous user through author attribution
      analysis. Although there has been previous work on the authorship attribution
      problem, there has been a dearth of research on automated authorship attribution
      on medical forums. The focus of the paper is to demonstrate that character-based
      author attribution works better than word-based methods in medical forums.
      OBJECTIVE: The goal was to build a system that accurately attributes authorship
      of messages posted on medical forums. The Authorship Attributor system uses text
      analysis techniques to crawl medical forums and automatically correlate messages
      written by the same authors. Authorship Attributor processes unstructured texts
      regardless of the document type, context, and content. METHODS: The messages were
      labeled by nicknames of the forum participants. We evaluated the system's
      performance through its accuracy on 6000 messages gathered from 2 medical forums
      on an in vitro fertilization (IVF) support website. RESULTS: Given 2 lists of
      candidate authors (30 and 50 candidates, respectively), we obtained an F score
      accuracy in detecting authors of 75% to 80% on messages containing 100 to 150
      words on average, and 97.9% on longer messages containing at least 300 words.
      CONCLUSIONS: Authorship can be successfully detected in short free-form messages
      posted on medical forums. This raises a concern about the meaningfulness of
      anonymous posting on such medical forums. Authorship attribution tools can be
      used to warn consumers wishing to post anonymously about the likelihood of their
      identity being determined.

PMID- 24091381
TI  - Optical sensor arrays for chemical sensing: the optoelectronic nose.
AB  - A comprehensive review is presented on the development and state of the art of
      colorimetric and fluorometric sensor arrays. Optical arrays based on
      chemoresponsive colorants (dyes and nanoporous pigments) probe the chemical
      reactivity of analytes, rather than their physical properties. This provides a
      high dimensionality to chemical sensing that permits high sensitivity (often down
      to ppb levels), impressive discrimination among very similar analytes and
      exquisite fingerprinting of extremely similar mixtures over a wide range of
      analyte types, both in the gas and liquid phases. 

PMID- 24091382
TI  - Analysis of the biological response of mouse liver (Mus musculus) exposed to
      As2O3 based on integrated -omics approaches.
AB  - Organic and inorganic mass spectrometries were used to investigate the
      biochemical response of mice (Mus musculus) to inorganic arsenic exposure using
      liver as the target organ. The toxicological effects of trivalent inorganic
      arsenic after oral administration (3 mg kg(-1) body weight and per day) were
      investigated over a period of 7 days using metallomics, metabonomics and redox
      proteomics approaches. Size-exclusion chromatography (SEC) with ICP-MS detection
      was combined with anion exchange chromatography (AEC) to characterize the
      biological response of the exposed mice. On the other hand, direct infusion mass
      spectrometry (DI-ESI-QTOF-MS) of polar and lipophilic extracts using positive and
      negative modes of acquisition (ESI+/ESI-) provided information about time
      dependent changes in endogenous metabolites identified by Partial Least Square
      Discriminant Analysis (PLS-DA). Finally, the study has been complemented with the
      evaluation of up/down-regulation of enzymes related to oxidative stress such as
      superoxide dismutase (SOD), glutathione reductase (GR), catalase (CAT) and
      peroxidases in connection with metal toxicity issues. The results show that the
      inorganic arsenic methylation in the liver may reach the saturation point upon
      chronic exposure to the element. On the other hand, SEC-ICP-MS coupling provided
      information about metal containing-proteins and metabolites related to arsenic
      exposure (metallomics) which has been correlated with the changes in the global
      metabolism (metabonomics), also considering their consequences on the redox
      status of protein and protein expression (redox proteomics). Our study shows that
      arsenic causes biochemical pathway alterations, such as energy metabolism (e.g.
      glycolysis, Krebs cycle), amino acid metabolism, choline metabolism and
      degradation of membrane phospholipids (apoptosis). This work illustrates the high
      reliability of the integrated use of organic mass spectrometry for the
      metabonomic study of biochemical effects induced by As2O3, with inorganic mass
      spectrometry for metallomic and speciation assessment of arsenic biomethylation
      in the liver of exposed mice, and redox proteomics to evaluate inhibition of
      enzymatic activity in different proteins such as superoxide dismutase (SOD),
      catalase (CAT) and glutathione reductase (GR) caused by this element. In
      conclusion, the integration of metallomics, metabolomics and redox proteomics
      results provides a more comprehensive evaluation about the biological response in
      experiments dealing with exposure to toxic metals. 

PMID- 24091383
TI  - High rates of child hypertension associated with obesity: a community survey in
      China, India and Mexico.
AB  - BACKGROUND: Hypertension is a significant risk factor for cardiovascular disease,
      and epidemiological evidence suggests that it is increasing in parallel with
      obesity in children and adolescents in low- and middle-income countries. AIM: To
      identify and determine the relationship between overweight, obesity and
      hypertension in a community sample of school children. METHODS: Anthropometric
      data were collected from 12,730 school children aged 12-18 years in China, India
      and Mexico as part of the Community Interventions for Health programme, an
      international study evaluating community interventions to reduce non-communicable
      disease by addressing the three main risk factors of tobacco use, unhealthy diets
      and physical inactivity. Logistic regression was used to examine the association
      of body mass index and gender and hypertension. RESULTS: Prevalence rates of
      hypertension were 5.2% in China, 10.1% in India and 14.1% in Mexico, and pre
      hypertension rates in China, India and Mexico were 13.4%, 9.4% and 11.2%,
      respectively. Overweight and obesity prevalence rates varied by country and were
      16.6% in China, 4.1% in India and 37.1% in Mexico. In all countries there was a
      significant association between overweight and obesity and rates of hypertension.
      Overweight children were 1.7-2.3 times more likely to be hypertensive and obese
      children 3.5-5.5 more likely to show hypertension than those of normal weight.
      CONCLUSIONS: Rates of hypertension and overweight and obesity are high in school
      children in China, India and Mexico, and increased bodyweight is a significant
      risk factor for hypertension.

PMID- 24091384
TI  - Revealing the ultrafast process behind the photoreduction of graphene oxide.
AB  - Effective techniques to reduce graphene oxide are in demand owing to the
      multitude of potential applications of this two-dimensional material. A very
      promising green method to do so is by exposure to ultraviolet irradiation.
      Unfortunately, the dynamics behind this reduction remain unclear. Here we perform
      a series of transient absorption experiments in an effort to develop and
      understand this process on a fundamental level. An ultrafast photoinduced chain
      reaction is observed to be responsible for the graphene oxide reduction. The
      reaction is initiated using a femtosecond ultraviolet pulse that photoionizes the
      solvent, liberating solvated electrons, which trigger the reduction. The present
      study reaches the fundamental time scale of the ultraviolet photoreduction in
      solution, which is revealed to be in the picosecond regime. 

PMID- 24091385
TI  - An ionic liquid-mediated electrochemiluminescent sensor for the detection of
      sulfur dioxide at the ppb level.
AB  - A novel portable SO2 gas sensor based on ionic liquid (IL) mediated
      electrochemiluminescence (ECL) for detecting SO2 at the ppb levels has been
      developed. The sensing system for SO2 detection is based on the strong quenching
      effect of SO2 on the ECL of the tris(2,2'-bipyridine)ruthenium(ii)
      (Ru(bpy)3(2+))/O2 coreactant system in the IL film. Over the potential window
      between -1.0 and +1.3 V, O2 can act as an effective coreactant for Ru(bpy)3(2+)
      ECL in ILs, giving a bright ECL emission. The ECL of the Ru(bpy)3(2+)/O2 system
      can be strongly inhibited by SO2 through the direct quenching of the excited
      state of the luminophore, i.e. Ru(bpy)3(2+)*, by SO2 molecules. The inhibited ECL
      intensity is proportional to the concentration of SO2 in the range from 40 to
      2000 ppb with a detection limit of 20 ppb. The proposed SO2 ECL sensor can be
      operated at room temperature and shows high selectivity, good reproducibility and
      long-term stability in a dry atmosphere. 

PMID- 24091386
TI  - Fractal markets hypothesis and the global financial crisis: wavelet power
      evidence.
AB  - We analyze whether the prediction of the fractal markets hypothesis about a
      dominance of specific investment horizons during turbulent times holds. To do so,
      we utilize the continuous wavelet transform analysis and obtained wavelet power
      spectra which give the crucial information about the variance distribution across
      scales and its evolution in time. We show that the most turbulent times of the
      Global Financial Crisis can be very well characterized by the dominance of short
      investment horizons which is in hand with the assertions of the fractal markets
      hypothesis. 

PMID- 24091387
TI  - A Janus role for MerTK in the outcome of septic shock.

PMID- 24091388
TI  - Tools for diagnosing delirium in the critically ill: is calibration needed for
      the less sedated patient?

PMID- 24091390
TI  - A recent survey on colon cancer detection techniques.
AB  - Colon cancer causes deaths of about half a million people every year. Common
      method of its detection is histopathological tissue analysis, which, though leads
      to vital diagnosis, is significantly correlated to the tiredness, experience, and
      workload of the pathologist. Researchers have been working since decades to get
      rid of manual inspection, and to develop trustworthy systems for detecting colon
      cancer. Several techniques, based on spectral/spatial analysis of colon biopsy
      images, and serum and gene analysis of colon samples, have been proposed in this
      regard. Due to rapid evolution of colon cancer detection techniques, a latest
      review of recent research in this field is highly desirable. The aim of this
      paper is to discuss various colon cancer detection techniques. In this survey, we
      categorize the techniques on the basis of the adopted methodology and underlying
      data set, and provide detailed description of techniques in each category.
      Additionally, this study provides an extensive comparison of various colon cancer
      detection categories, and of multiple techniques within each category. Further,
      most of the techniques have been evaluated on similar data set to provide a fair
      performance comparison. Analysis reveals that neither of the techniques is
      perfect; however, research community is progressively inching toward the finest
      possible solution. 

PMID- 24091389
TI  - Breath analysis in pulmonary arterial hypertension.
AB  - BACKGROUND: Pulmonary arterial hypertension (PAH) is a progressive and
      devastating condition characterized by vascular cell proliferation and is
      associated with several metabolic derangements. We hypothesized that metabolic
      derangements in PAH can be detected by measuring metabolic by-products in exhaled
      breath. METHODS: We collected breath and blood samples from patients with PAH at
      the time of right-sided heart catheterization (n=31) and from healthy control
      subjects (n=34). Breath was analyzed by selected ion flow tube-mass spectrometry
      in predetermined training and validation cohorts. RESULTS: Patients with PAH were
      51.5+/-14 years old, and 27 were women (85%). Control subjects were 38+/-13 years
      old, and 22 were women (65%). Discriminant analysis in the training set
      identified three ion peaks (H3O+29+, NO+56+, and O2+98+) and the variable age
      that correctly classified 88.9% of the individuals. In an independent validation
      cohort, 82.8% of the individuals were classified correctly. The concentrations of
      the volatile organic compounds 2-propanol, acetaldehyde, ammonia, ethanol,
      pentane, 1-decene, 1-octene, and 2-nonene were different in patients with PAH
      compared with control subjects. Exhaled ammonia was higher in patients with PAH
      (median [interquartile range]: 94.7 parts per billion (ppb) [70-129 ppb] vs 60.9
      ppb [46-77 ppb], P<.001) and was associated with right atrial pressure (rho=0.57,
      P<.001), mean pulmonary artery pressure (rho=0.43, P=.015), cardiac index by
      thermodilution (rho=-0.39, P=.03), pulmonary vascular resistance (rho=0.40,
      P=.04), mixed venous oxygen (rho=-0.59, P<.001), and right ventricular dilation
      (rho=0.42, P=.03). CONCLUSIONS: Breathprint is different between patients with
      PAH and healthy control subjects. Several specific compounds, including ammonia,
      were elevated in the breath of patients with PAH. Exhaled ammonia levels
      correlated with severity of disease.

PMID- 24091391
TI  - A combination of feature extraction methods with an ensemble of different
      classifiers for protein structural class prediction problem.
AB  - Better understanding of structural class of a given protein reveals important
      information about its overall folding type and its domain. It can also be
      directly used to provide critical information on general tertiary structure of a
      protein which has a profound impact on protein function determination and drug
      design. Despite tremendous enhancements made by pattern recognition-based
      approaches to solve this problem, it still remains as an unsolved issue for
      bioinformatics that demands more attention and exploration. In this study, we
      propose a novel feature extraction model that incorporates physicochemical and
      evolutionary-based information simultaneously. We also propose overlapped
      segmented distribution and autocorrelation-based feature extraction methods to
      provide more local and global discriminatory information. The proposed feature
      extraction methods are explored for 15 most promising attributes that are
      selected from a wide range of physicochemical-based attributes. Finally, by
      applying an ensemble of different classifiers namely, Adaboost.M1, LogitBoost,
      naive Bayes, multilayer perceptron (MLP), and support vector machine (SVM) we
      show enhancement of the protein structural class prediction accuracy for four
      popular benchmarks. 

PMID- 24091392
TI  - Accuracy guarantees for phylogeny reconstruction algorithms based on balanced
      minimum evolution.
AB  - Distance-based phylogenetic methods attempt to reconstruct an accurate
      phylogenetic tree from an estimated matrix of pairwise distances between taxa.
      This paper examines two distance-based algorithms (GreedyBME and FastME) that are
      based on the principle of minimizing the balanced minimum evolution score of the
      output tree in relation to the given estimated distance matrix. This is also the
      principle that underlies the neighbor-joining (NJ) algorithm. We show that
      GreedyBME and FastME both reconstruct the entire correct tree if the input data
      are quartet consistent, and also that if the maximum error of any distance
      estimate is epsilon, then both algorithms output trees containing all
      sufficiently long edges of the true tree: those having length at least 3epsilon.
      That is to say, the algorithms have edge safety radius 1/3. In contrast, quartet
      consistency of the data is not sufficient to guarantee the NJ algorithm
      reconstructs the correct tree, and moreover, the NJ algorithm has edge safety
      radius of 1/4: Only edges of the true tree of length at least 4epsilon can be
      guaranteed to appear in the output. These results give further theoretical
      support to the experimental evidence suggesting FastME is a more suitable
      distance-based phylogeny reconstruction method than the NJ algorithm.

PMID- 24091393
TI  - Boolean networks with multiexpressions and parameters.
AB  - To model biological systems using networks, it is desirable to allow more than
      two levels of expression for the nodes and to allow the introduction of
      parameters. Various modeling and simulation methods addressing these needs using
      Boolean models, both synchronous and asynchronous, have been proposed in the
      literature. However, analytical study of these more general Boolean networks
      models is lagging. This paper aims to develop a concise theory for these
      different Boolean logic-based modeling methods. Boolean models for networks where
      each node can have more than two levels of expression and Boolean models with
      parameters are defined algebraically with examples provided. Certain classes of
      random asynchronous Boolean networks and deterministic moduli asynchronous
      Boolean networks are investigated in detail using the setting introduced in this
      paper. The derived theorems provide a clear picture for the attractor structures
      of these asynchronous Boolean networks. 

PMID- 24091394
TI  - Comparison of feature selection methods for cross-laboratory microarray analysis.
AB  - The amount of gene expression data of microarray has grown exponentially. To
      apply them for extensive studies, integrated analysis of cross-laboratory (cross
      lab) data becomes a trend, and thus, choosing an appropriate feature selection
      method is an essential issue. This paper focuses on feature selection for
      Affymetrix (Affy) microarray studies across different labs. We investigate four
      feature selection methods: $(t)$-test, significance analysis of microarrays
      (SAM), rank products (RP), and random forest (RF). The four methods are applied
      to acute lymphoblastic leukemia, acute myeloid leukemia, breast cancer, and lung
      cancer Affy data which consist of three cross-lab data sets each. We utilize a
      rank-based normalization method to reduce the bias from cross-lab data sets.
      Training on one data set or two combined data sets to test the remaining data
      set(s) are both considered. Balanced accuracy is used for prediction evaluation.
      This study provides comprehensive comparisons of the four feature selection
      methods in cross-lab microarray analysis. Results show that SAM has the best
      classification performance. RF also gets high classification accuracy, but it is
      not as stable as SAM. The most naive method is $(t)$-test, but its performance is
      the worst among the four methods. In this study, we further discuss the influence
      from the number of training samples, the number of selected genes, and the issue
      of unbalanced data sets. 

PMID- 24091395
TI  - Designing integrated computational biology pipelines visually.
AB  - The long-term cost of developing and maintaining a computational pipeline that
      depends upon data integration and sophisticated workflow logic is too high to
      even contemplate "what if" or ad hoc type queries. In this paper, we introduce a
      novel application building interface for computational biology research, called
      VizBuilder, by leveraging a recent query language called BioFlow for life
      sciences databases. Using VizBuilder, it is now possible to develop ad hoc
      complex computational biology applications at throw away costs. The underlying
      query language supports data integration and workflow construction almost
      transparently and fully automatically, using a best effort approach. Users
      express their application by drawing it with VizBuilder icons and connecting them
      in a meaningful way. Completed applications are compiled and translated as
      BioFlow queries for execution by the data management system LifeDB, for which
      VizBuilder serves as a front end. We discuss VizBuilder features and
      functionalities in the context of a real life application after we briefly
      introduce BioFlow. The architecture and design principles of VizBuilder are also
      discussed. Finally, we outline future extensions of VizBuilder. To our knowledge,
      VizBuilder is a unique system that allows visually designing computational
      biology pipelines involving distributed and heterogeneous resources in an ad hoc
      manner.

PMID- 24091396
TI  - Gelsius: a literature-based workflow for determining quantitative associations
      between genes and biological processes.
AB  - An effective knowledge extraction and quantification methodology from biomedical
      literature would allow the researcher to organize and analyze the results of high
      throughput experiments on microarrays and next-generation sequencing
      technologies. Despite the large amount of raw information available on the web, a
      tool able to extract a measure of the correlation between a list of genes and
      biological processes is not yet available. In this paper, we present Gelsius, a
      workflow that incorporates biomedical literature to quantify the correlation
      between genes and terms describing biological processes. To achieve this target,
      we build different modules focusing on query expansion and document
      cononicalization. In this way, we reached to improve the measurement of
      correlation, performed using a latent semantic analysis approach. To the best of
      our knowledge, this is the first complete tool able to extract a measure of genes
      biological processes correlation from literature. We demonstrate the
      effectiveness of the proposed workflow on six biological processes and a set of
      genes, by showing that correlation results for known relationships are in
      accordance with definitions of gene functions provided by NCI Thesaurus. On the
      other side, the tool is able to propose new candidate relationships for later
      experimental validation. The tool is available at
      >http://bioeda1.polito.it:8080/medSearchServlet/. 

PMID- 24091397
TI  - Generalized query-based active learning to identify differentially methylated
      regions in DNA.
AB  - Active learning is a supervised learning technique that reduces the number of
      examples required for building a successful classifier, because it can choose the
      data it learns from. This technique holds promise for many biological domains in
      which classified examples are expensive and time-consuming to obtain. Most
      traditional active learning methods ask very specific queries to the Oracle
      (e.g., a human expert) to label an unlabeled example. The example may consist of
      numerous features, many of which are irrelevant. Removing such features will
      create a shorter query with only relevant features, and it will be easier for the
      Oracle to answer. We propose a generalized query-based active learning (GQAL)
      approach that constructs generalized queries based on multiple instances. By
      constructing appropriately generalized queries, we can achieve higher accuracy
      compared to traditional active learning methods. We apply our active learning
      method to find differentially DNA methylated regions (DMRs). DMRs are DNA
      locations in the genome that are known to be involved in tissue differentiation,
      epigenetic regulation, and disease. We also apply our method on 13 other data
      sets and show that our method is better than another popular active learning
      technique. 

PMID- 24091398
TI  - GenomeTools: a comprehensive software library for efficient processing of
      structured genome annotations.
AB  - Genome annotations are often published as plain text files describing genomic
      features and their subcomponents by an implicit annotation graph. In this paper,
      we present the GenomeTools, a convenient and efficient software library and
      associated software tools for developing bioinformatics software intended to
      create, process or convert annotation graphs. The GenomeTools strictly follow the
      annotation graph approach, offering a unified graph-based representation. This
      gives the developer intuitive and immediate access to genomic features and tools
      for their manipulation. To process large annotation sets with low memory
      overhead, we have designed and implemented an efficient pull-based approach for
      sequential processing of annotations. This allows to handle even the largest
      annotation sets, such as a complete catalogue of human variations. Our object
      oriented C-based software library enables a developer to conveniently implement
      their own functionality on annotation graphs and to integrate it into larger
      workflows, simultaneously accessing compressed sequence data if required. The
      careful C implementation of the GenomeTools does not only ensure a light-weight
      memory footprint while allowing full sequential as well as random access to the
      annotation graph, but also facilitates the creation of bindings to a variety of
      script programming languages (like Python and Ruby) sharing the same interface. 

PMID- 24091399
TI  - Hybrid fuzzy cluster ensemble framework for tumor clustering from biomolecular
      data.
AB  - Cancer class discovery using biomolecular data is one of the most important tasks
      for cancer diagnosis and treatment. Tumor clustering from gene expression data
      provides a new way to perform cancer class discovery. Most of the existing
      research works adopt single-clustering algorithms to perform tumor clustering is
      from biomolecular data that lack robustness, stability, and accuracy. To further
      improve the performance of tumor clustering from biomolecular data, we introduce
      the fuzzy theory into the cluster ensemble framework for tumor clustering from
      biomolecular data, and propose four kinds of hybrid fuzzy cluster ensemble
      frameworks (HFCEF), named as HFCEF-I, HFCEF-II, HFCEF-III, and HFCEF-IV,
      respectively, to identify samples that belong to different types of cancers. The
      difference between HFCEF-I and HFCEF-II is that they adopt different ensemble
      generator approaches to generate a set of fuzzy matrices in the ensemble.
      Specifically, HFCEF-I applies the affinity propagation algorithm (AP) to perform
      clustering on the sample dimension and generates a set of fuzzy matrices in the
      ensemble based on the fuzzy membership function and base samples selected by AP.
      HFCEF-II adopts AP to perform clustering on the attribute dimension, generates a
      set of subspaces, and obtains a set of fuzzy matrices in the ensemble by
      performing fuzzy c-means on subspaces. Compared with HFCEF-I and HFCEF-II, HFCEF
      III and HFCEF-IV consider the characteristics of HFCEF-I and HFCEF-II. HFCEF-III
      combines HFCEF-I and HFCEF-II in a serial way, while HFCEF-IV integrates HFCEF-I
      and HFCEF-II in a concurrent way. HFCEFs adopt suitable consensus functions, such
      as the fuzzy c-means algorithm or the normalized cut algorithm (Ncut), to
      summarize generated fuzzy matrices, and obtain the final results. The experiments
      on real data sets from UCI machine learning repository and cancer gene expression
      profiles illustrate that 1) the proposed hybrid fuzzy cluster ensemble frameworks
      work well on real data sets, especially biomolecular data, and 2) the proposed
      approaches are able to provide more robust, stable, and accurate results when
      compared with the state-of-the-art single clustering algorithms and traditional
      cluster ensemble approaches. 

PMID- 24091400
TI  - Inference of gene regulatory networks with variable time delay from time-series
      microarray data.
AB  - Regulatory interactions among genes and gene products are dynamic processes and
      hence modeling these processes is of great interest. Since genes work in a
      cascade of networks, reconstruction of gene regulatory network (GRN) is a crucial
      process for a thorough understanding of the underlying biological interactions.
      We present here an approach based on pairwise correlations and lasso to infer the
      GRN, taking into account the variable time delays between various genes. The
      proposed method is applied to both synthetic and real data sets, and the results
      on synthetic data show that the proposed approach outperforms the current
      methods. Further, the results using real data are more consistent with the
      existing knowledge concerning the possible gene interactions. 

PMID- 24091401
TI  - Informative SNPs selection based on two-locus and multilocus linkage
      disequilibrium: criteria of max-correlation and min-redundancy.
AB  - Currently, there are lots of methods to select informative SNPs for haplotype
      reconstruction. However, there are still some challenges that render them
      ineffective for large data sets. First, some traditional methods belong to
      wrappers which are of high computational complexity. Second, some methods ignore
      linkage disequilibrium that it is hard to interpret selection results. In this
      study, we innovatively derive optimization criteria by combining two-locus and
      multilocus LD measure to obtain the criteria of Max-Correlation and Min
      Redundancy (MCMR). Then, we use a greedy algorithm to select the candidate set of
      informative SNPs constrained by the criteria. Finally, we use backward scheme to
      refine the candidate subset. We separately use small and middle (>1,000 SNPs)
      data sets to evaluate MCMR in terms of the reconstuction accuracy, the time
      complexity, and the compactness. Additionally, to demonstrate that MCMR is
      practical for large data sets, we design a parameter w to adapt to various
      platforms and introduce another replacement scheme for larger data sets, which
      sharply narrow down the computational complexity of evaluating the reconstruct
      ratio. Then, we first apply our method based on haplotype reconstruction for
      large size (>5,000 SNPs) data sets. The results confirm that MCMR leads to
      promising improvement in informative SNPs selection and prediction accuracy.

PMID- 24091402
TI  - Modeling associated protein-DNA pattern discovery with unified scores.
AB  - Understanding protein-DNA interactions, specifically transcription factor (TF)
      and transcription factor binding site (TFBS) bindings, is crucial in deciphering
      gene regulation. The recent associated TF-TFBS pattern discovery combines one
      sided motif discovery on both the TF and the TFBS sides. Using sequences only, it
      identifies the short protein-DNA binding cores available only in high-resolution
      3D structures. The discovered patterns lead to promising subtype and disease
      analysis applications. While the related studies use either association rule
      mining or existing TFBS annotations, none has proposed any formal unified (both
      sided) model to prioritize the top verifiable associated patterns. We propose the
      unified scores and develop an effective pipeline for associated TF-TFBS pattern
      discovery. Our stringent instance-level evaluations show that the patterns with
      the top unified scores match with the binding cores in 3D structures considerably
      better than the previous works, where up to 90 percent of the top 20 scored
      patterns are verified. We also introduce extended verification from literature
      surveys, where the high unified scores correspond to even higher verification
      percentage. The top scored patterns are confirmed to match the known WRKY binding
      cores with no available 3D structures and agree well with the top binding
      affinities of in vivo experiments. 

PMID- 24091403
TI  - Multiobjective identification of controlling areas in neuronal networks.
AB  - In this paper, we investigate the multiobjective identification of controlling
      areas in the neuronal network of a cat's brain by considering two measures of
      controllability simultaneously. By utilizing nondominated sorting mechanisms and
      composite differential evolution (CoDE), a reference-point-based nondominated
      sorting composite differential evolution (RP-NSCDE) is developed to tackle the
      multiobjective identification of controlling areas in the neuronal network. The
      proposed RP-NSCDE shows its promising performance in terms of accuracy and
      convergence speed, in comparison to nondominated sorting genetic algorithms II.
      The proposed method is also compared with other representative statistical
      methods in the complex network theory, single objective, and constraint
      optimization methods to illustrate its effectiveness and reliability. It is shown
      that there exists a tradeoff between minimizing two objectives, and therefore
      pareto fronts (PFs) can be plotted. The developed approaches and findings can
      also be applied to coordination control of various kinds of real-world complex
      networks including biological networks and social networks, and so on. 

PMID- 24091404
TI  - On the neighborhoods of trees.
AB  - Tree rearrangement operations typically induce a metric on the space of
      phylogenetic trees. One important property of these metrics is the size of the
      neighborhood, that is, the number of trees exactly one operation from a given
      tree. We present an exact expression for the size of the TBR (tree bisection and
      reconnection) neighborhood, thus answering a question first posed by Allen and
      Steel . In addition, we also obtain a characterization of the extremal trees
      whose TBR neighborhoods are maximized and minimized. 

PMID- 24091405
TI  - Protein complex prediction in large ontology attributed protein-protein
      interaction networks.
AB  - Protein complexes are important for unraveling the secrets of cellular
      organization and function. Many computational approaches have been developed to
      predict protein complexes in protein-protein interaction (PPI) networks. However,
      most existing approaches focus mainly on the topological structure of PPI
      networks, and largely ignore the gene ontology (GO) annotation information. In
      this paper, we constructed ontology attributed PPI networks with PPI data and GO
      resource. After constructing ontology attributed networks, we proposed a novel
      approach called CSO (clustering based on network structure and ontology attribute
      similarity). Structural information and GO attribute information are
      complementary in ontology attributed networks. CSO can effectively take advantage
      of the correlation between frequent GO annotation sets and the dense subgraph for
      protein complex prediction. Our proposed CSO approach was applied to four
      different yeast PPI data sets and predicted many well-known protein complexes.
      The experimental results showed that CSO was valuable in predicting protein
      complexes and achieved state-of-the-art performance. 

PMID- 24091406
TI  - Reformulated Kemeny optimal aggregation with application in consensus ranking of
      microRNA targets.
AB  - MicroRNAs are very recently discovered small noncoding RNAs, responsible for
      negative regulation of gene expression. Members of this endogenous family of
      small RNA molecules have been found implicated in many genetic disorders. Each
      microRNA targets tens to hundreds of genes. Experimental validation of target
      genes is a time- and cost-intensive procedure. Therefore, prediction of microRNA
      targets is a very important problem in computational biology. Though, dozens of
      target prediction algorithms have been reported in the past decade, they disagree
      significantly in terms of target gene ranking (based on predicted scores). Rank
      aggregation is often used to combine multiple target orderings suggested by
      different algorithms. This technique has been used in diverse fields including
      social choice theory, meta search in web, and most recently, in bioinformatics.
      Kemeny optimal aggregation (KOA) is considered the more profound objective for
      rank aggregation. The consensus ordering obtained through Kemeny optimal
      aggregation incurs minimum pairwise disagreement with the input orderings.
      Because of its computational intractability, heuristics are often formulated to
      obtain a near optimal consensus ranking. Unlike its real time use in meta search,
      there are a number of scenarios in bioinformatics (e.g., combining microRNA
      target rankings, combining disease-related gene rankings obtained from microarray
      experiments) where evolutionary approaches can be afforded with the ambition of
      better optimization. We conjecture that an ideal consensus ordering should have
      its total disagreement shared, as equally as possible, with the input orderings.
      This is also important to refrain the evolutionary processes from getting stuck
      to local extremes. In the current work, we reformulate Kemeny optimal aggregation
      while introducing a trade-off between the total pairwise disagreement and its
      distribution. A simulated annealing-based implementation of the proposed
      objective has been found effective in context of microRNA target ranking.
      Supplementary data and source code link are available at:
      >http://www.isical.ac.in/bioinfo_miu/ieee_tcbb_kemeny.rar. 

PMID- 24091407
TI  - Sequence-based prediction of microRNA-binding residues in proteins using cost
      sensitive Laplacian support vector machines.
AB  - The recognition of microRNA (miRNA)-binding residues in proteins is helpful to
      understand how miRNAs silence their target genes. It is difficult to use existing
      computational method to predict miRNA-binding residues in proteins due to the
      lack of training examples. To address this issue, unlabeled data may be exploited
      to help construct a computational model. Semisupervised learning deals with
      methods for exploiting unlabeled data in addition to labeled data automatically
      to improve learning performance, where no human intervention is assumed. In
      addition, miRNA-binding proteins almost always contain a much smaller number of
      binding than nonbinding residues, and cost-sensitive learning has been deemed as
      a good solution to the class imbalance problem. In this work, a novel model is
      proposed for recognizing miRNA-binding residues in proteins from sequences using
      a cost-sensitive extension of Laplacian support vector machines (CS-LapSVM) with
      a hybrid feature. The hybrid feature consists of evolutionary information of the
      amino acid sequence (position-specific scoring matrices), the conservation
      information about three biochemical properties (HKM) and mutual interaction
      propensities in protein-miRNA complex structures. The CS-LapSVM receives good
      performance with an F1 score of 26.23 +/- 2.55% and an AUC value of 0.805 +/-
      0.020 superior to existing approaches for the recognition of RNA-binding
      residues. A web server called SARS is built and freely available for academic
      usage.

PMID- 24091408
TI  - Studying the role of lipid rafts on protein receptor bindings with cellular
      automata.
AB  - It is widely accepted that lipid rafts promote receptor clustering and thereby
      facilitate signaling transduction. The role of lipid rafts in inducing and
      promoting receptor accumulation within the cell membrane has been explored by
      several computational and experimental studies. However, it remains unclear
      whether lipid rafts influence the recruitment and binding of proteins from the
      cytosol as well. To provide an answer to this question a spatial membrane model
      has been developed based on cellular automata. Our results indicate that lipid
      rafts indeed influence protein receptor bindings. In particular processes with
      slow dissociation and binding kinetics are promoted by lipid rafts, whereas fast
      binding processes are slightly hampered. However, the impact depends on a variety
      of parameters, such as the size and mobility of the lipid rafts, the induced slow
      down of receptors within rafts, and also the dissociation and binding kinetics of
      the cytosolic proteins. Thus, for any individual signaling pathway the influence
      of lipid rafts on protein binding might be different. To facilitate analyzing
      this influence given a specific pathway, our approach has been generalized into
      LiRaM, a modeling and simulation tool for lipid rafts models. 

PMID- 24091409
TI  - Systematic analysis of the mechanisms of virus-triggered type I IFN signaling
      pathways through mathematical modeling.
AB  - Based on biological experimental data, we developed a mathematical model of the
      virus-triggered signaling pathways that lead to induction of type I IFNs and
      systematically analyzed the mechanisms of the cellular antiviral innate immune
      responses, including the negative feedback regulation of ISG56 and the positive
      feedback regulation of IFNs. We found that the time between 5 and 48 hours after
      viral infection is vital for the control and/or elimination of the virus from the
      host cells and demonstrated that the ISG56-induced inhibition of MITA activation
      is stronger than the ISG56-induced inhibition of TBK1 activation. The global
      parameter sensitivity analysis suggests that the positive feedback regulation of
      IFNs is very important in the innate antiviral system. Furthermore, the
      robustness of the innate immune signaling network was demonstrated using a new
      robustness index. These results can help us understand the mechanisms of the
      virus-induced innate immune response at a system level and provide instruction
      for further biological experiments. 

PMID- 24091410
TI  - Utilizing both topological and attribute information for protein complex
      identification in PPI networks.
AB  - Many computational approaches developed to identify protein complexes in protein
      protein interaction (PPI) networks perform their tasks based only on network
      topologies. The attributes of the proteins in the networks are usually ignored.
      As protein attributes within a complex may also be related to each other, we have
      developed a PCIA algorithm to take into consideration both such information and
      network topology in the identification process of protein complexes. Given a PPI
      network, PCIA first finds information about the attributes of the proteins in a
      PPI network in the Gene Ontology databases and uses such information for the
      identification of protein complexes. PCIA then computes a Degree of Association
      measure for each pair of interacting proteins to quantitatively determine how
      much their attribute values associate with each other. Based on this association
      measure, PCIA is able to discover dense graph clusters consisting of proteins
      whose attribute values are significantly closer associated with each other. PCIA
      has been tested with real data and experimental results seem to indicate that
      attributes of the proteins in the same complex do have some association with each
      other and, therefore, that protein complexes can be more accurately identified
      when protein attributes are taken into consideration. 

PMID- 24091411
TI  - A new approach to implement absorbing boundary condition in biomolecular
      electrostatics.
AB  - This paper discusses a novel approach to employ the absorbing boundary condition
      in conjunction with the finite-element method (FEM) in biomolecular
      electrostatics. The introduction of Bayliss-Turkel absorbing boundary operators
      in electromagnetic scattering problem has been incorporated by few researchers.
      However, in the area of biomolecular electrostatics, this boundary condition has
      not been investigated yet. The objective of this paper is twofold. First, to
      solve nonlinear Poisson-Boltzmann equation using Newton's method and second, to
      find an efficient and acceptable solution with minimum number of unknowns. In
      this work, a Galerkin finite-element formulation is used along with a Bayliss
      Turkel absorbing boundary operator that explicitly accounts for the open field
      problem by mapping the Sommerfeld radiation condition from the far field to near
      field. While the Bayliss-Turkel condition works well when the artificial boundary
      is far from the scatterer, an acceptable tolerance of error can be achieved with
      the second order operator. Numerical results on test case with simple sphere show
      that the treatment is able to reach the same level of accuracy achieved by the
      analytical method while using a lower grid density. Bayliss-Turkel absorbing
      boundary condition (BTABC) combined with the FEM converges to the exact solution
      of scattering problems to within discretization error. 

PMID- 24091412
TI  - Computer-aided biophysical modeling: a quantitative approach to complex
      biological systems.
AB  - When dealing with the biophysics of tumors, analytical and numerical modeling
      tools have long been regarded as potentially useful but practically immature
      tools. Further developments could not just overturn this predicament, but lead to
      completely new perspectives in biology. Here, we give an account of our own
      computational tool and how we have put it to good use, and we discuss a
      paradigmatic example to outline a path to making cell biology more quantitative
      and predictive. 

PMID- 24091413
TI  - Quantitative prediction of peptide binding to HLA-DP1 protein.
AB  - The exogenous proteins are processed by the host antigen-processing cells.
      Peptidic fragments of them are presented on the cell surface bound to the major
      hystocompatibility complex (MHC) molecules class II and recognized by the CD4+ T
      lymphocytes. The MHC binding is considered as the crucial prerequisite for T-cell
      recognition. Only peptides able to form stable complexes with the MHC proteins
      are recognized by the T-cells. These peptides are known as T-cell epitopes. All T
      cell epitopes are MHC binders, but not all MHC binders are T-cell epitopes. The T
      cell epitope prediction is one of the main priorities of immunoinformatics. In
      the present study, three chemometric techniques are combined to derive a model
      for in silico prediction of peptide binding to the human MHC class II protein HLA
      DP1. The structures of a set of known peptide binders are described by amino acid
      z-descriptors. Data are processed by an iterative self-consisted algorithm using
      the method of partial least squares, and a quantitative matrix (QM) for peptide
      binding prediction to HLA-DP1 is derived. The QM is validated by two sets of
      proteins and showed an average accuracy of 86 percent. 

PMID- 24091414
TI  - Dysferlin is a newly identified binding partner of AbetaPP and it co-aggregates
      with amyloid-beta42 within sporadic inclusion-body myositis (s-IBM) muscle
      fibers.

PMID- 24091415
TI  - Pharmacists' perspectives on HIV testing in community pharmacies.
AB  - OBJECTIVE: To assess the feasibility, readiness, and acceptability of offering
      rapid human immunodeficiency virus (HIV) testing in community pharmacies. DESIGN:
      Qualitative study. SETTING: Community pharmacies in Indiana from May to September
      2012. PARTICIPANTS: 17 licensed community pharmacists. INTERVENTION:
      Semistructured interviews among a convenience sample of community pharmacists.
      MAIN OUTCOME MEASURES: Community pharmacists' self-reported attitudes toward
      rapid HIV testing in community pharmacies, perceptions of peer acceptability, and
      opinions about readiness for implementation of the practice in community
      pharmacies. RESULTS: Participants accepted the idea of pharmacy-based HIV
      testing, describing it as accessible, convenient, and nonstigmatizing.
      Acceptability was closely linked to positive patient relationships and pharmacist
      comfort with consultation. Identified challenges to pharmacy-based HIV testing
      included staffing issues, uneasiness with delivering positive test results, lack
      of information needed to link patients to care, insufficient consulting space,
      and need for additional training. Participants indicated that peer beliefs about
      the acceptability of pharmacist-based HIV testing would vary but that more
      recently trained pharmacists likely would be more accepting of the practice.
      CONCLUSION: Most participants felt that offering HIV testing was a reasonable
      addition to the evolving role of the community pharmacist, pending resolution of
      personal and institutional barriers.

PMID- 24091416
TI  - Extracortical plate fixation with new plate inserts and cerclage wires for the
      treatment of periprosthetic hip fractures.
AB  - PURPOSE: Fixation of periprosthetic hip fractures with intracortical anchorage
      might not be feasible in cases with bulky implants and/or poor bone stock.
      METHODS: Rotational stability of new plate inserts with extracortical anchorage
      for cerclage fixation was measured and compared to the stability found using a
      standard technique in a biomechanical setup using a torsion testing machine. In a
      synthetic PUR bone model, transverse fractures were fixed distally using screws
      and proximally by wire cerclages attached to the plates using "new"
      (extracortical anchorage) or "standard" (intracortical anchorage) plate inserts.
      Time to fracture consolidation and complications were assessed in a consecutive
      series of 18 patients (18 female; mean age 81 years, range 55-92) with
      periprosthetic hip fractures (ten type B1, eight type C-Vancouver) treated with
      the new device between July 2003 and July 2010. RESULTS: The "new" device showed
      a higher rotational stability than the "standard" technique (p < 0.001).
      Fractures showed radiographic consolidation after 14 +/- 5 weeks (mean +/- SD)
      postoperatively in patients. Revision surgery was necessary in four patients,
      unrelated to the new technique. CONCLUSION: In periprosthetic hip fractures in
      which fixation with intracortical anchorage using conventional means might be
      difficult due to bulky revision stems and/or poor bone stock, the new device may
      be an addition to the range of existing implants.

PMID- 24091417
TI  - A comparative biomechanical study of proximal femoral nail (InterTAN) and
      proximal femoral nail antirotation for intertrochanteric fractures.
AB  - PURPOSE: The purpose of this study was to compare the biomechanical strength of
      the cephalomedullary nail InterTAN in cases of intertrochanteric fractures with
      the commonly used PFNA. METHODS: Sixteen fresh specimens of the proximal femur
      were used as intertrochanteric fracture models and were fixed using two fixation
      devices: the new proximal femoral nail (InterTAN) and proximal femoral nail
      antirotation (PFNA). An intertrochanteric fracture was created in composite bone
      models. Each specimen was loaded to simulate single leg stance while stiffness,
      migration (cut out), compressive force across the fracture site, and distal
      fragment rotation were monitored. The different internal fixation methods were
      tested by an experimental press analysis. RESULTS: Results of tests for femoral
      strength, stiffness, stability, and bearing capacity demonstrated that the
      biomechanical function of InterTAN was better than that of PFNA (P < 0.05).
      Compared with the PFNA nail, InterTAN showed increased strength, stiffness, and
      resistance torque of 30%, 15%, and 27%, respectively. CONCLUSION: Comparison of
      the treatment of intertrochanteric fractures with InterTAN and PFNA internal
      fixation showed that the InterTAN yielded improvement relative to the PFNA.
      InterTAN has a firmer and biomechanically superior performance and is therefore
      an ideal internal fixation method for treating intertrochanteric fractures.
      Additional research in osteopenic bone is necessary to comprehensively
      characterize the effects of the design enhancements of these two implants.

PMID- 24091418
TI  - Closed/open reduction and titanium elastic nails for severely displaced proximal
      humeral fractures in children.
AB  - PURPOSE: The aim of the study was to evaluate the clinical outcome of closed/open
      reduction and titanium elastic nails (TENs) in children with severely displaced
      proximal humeral fractures. METHODS: A retrospective study was performed on 37
      children suffering from proximal humeral fracture between April 2009 and July
      2012. All these patients were treated by closed or open reduction with TEN
      fixation. The healing process was assessed by radiographic and clinical follow-up
      for up to 36 months. Radiographic assessment was performed on the scheduled
      follow-ups to examine fracture healing, remodelling, bone growth and residual
      deformity. The clinical outcomes were evaluated using the Neer shoulder score and
      patients' satisfaction report at the final follow-up. Complications related to
      the treatment were also recorded. RESULTS: All patients had a mean follow-up
      period of 24 months (12-36) after surgery. All fractures were healed,
      radiologically, at a median time of eight weeks (seven to ten weeks). There were
      no major complications related to the treatment. Two patients complained about
      skin irritation around the sides of the prominent distal ends of the nails.
      Implant removal took place at an average of 5.8 months post-operatively as an
      outpatient procedure. There were no observed complications in association with
      the removal of the hardware. At the final follow-up, the mean Neer shoulder score
      was 96.65 (range 83-100). Thirty patients were very satisfied with their surgical
      outcomes and the remaining seven were satisfied. Function of the affected arm
      returned to normal at the end of the follow-up period in all cases. CONCLUSIONS:
      Combining closed or open reduction with TEN fixation is recommended for treating
      severely displaced proximal humeral fractures in children. Our data showed
      evidence of satisfactory outcomes with a low complication rate and a fast return
      to normal mobility of the affected arms.

PMID- 24091419
TI  - Prevalence of first-step mutants among levofloxacin-susceptible isolates of
      Streptococcus pneumoniae in north Lebanon.
AB  - Resistance of Streptococcus pneumoniae to fluoroquinolones arises by stepwise
      accumulation of spontaneous point mutations in the quinolone-resistance
      determining regions (QRDRs). Fluoroquinolones treatment of infections caused by
      first-step mutants (pre-resistant) can lead to the selection of resistant
      isolates, resulting in treatment failure. First-step mutants cannot however be
      reliably detected by routine resistance testing. Levofloxacin has been used as a
      surrogate marker to predict fluoroquinolone susceptibility in clinical
      laboratories. By use of a PCR followed by pyrosequencing, we examined 45
      levofloxacin-susceptible pneumococcal strains [minimal inhibitory concentration
      (MIC) < 0.5 MUg/ml] for first-step parC and parE mutations in the QRDR: 51.2% of
      isolates were recovered from pulmonary and nasal secretions, 22.2% from blood,
      24.4% from ear and eye discharge, and 2.2% from cerebrospinal fluid. The results
      showed that three strains (6.6%) had first-step parC (Asp83-Asn) or parE (Asp435
      Asn) mutations. This test could be useful for some high-risk patients or in
      national surveys.

PMID- 24091421
TI  - Correction.

PMID- 24091420
TI  - Mutations in palmitoyl-protein thioesterase 1 alter exocytosis and endocytosis at
      synapses in Drosophila larvae.
AB  - Infantile-onset neuronal ceroid lipofuscinosis (INCL) is a severe pediatric
      neurodegenerative disorder produced by mutations in the gene encoding palmitoyl
      protein thioesterase 1 (Ppt1). This enzyme is responsible for the removal of a
      palmitate group from its substrate proteins, which may include presynaptic
      proteins like SNAP-25, cysteine string protein (CSP), dynamin, and synaptotagmin.
      The fruit fly, Drosophila melanogaster, has been a powerful model system for
      studying the functions of these proteins and the molecular basis of neurological
      disorders like the NCLs. Genetic modifier screens and tracer uptake studies in
      Ppt1 mutant larval garland cells have suggested that Ppt1 plays a role in
      endocytic trafficking. We have extended this analysis to examine the involvement
      of Ppt1 in synaptic function at the Drosophila larval neuromuscular junction
      (NMJ). Mutations in Ppt1 genetically interact with temperature sensitive
      mutations in the Drosophila dynamin gene shibire, accelerating the paralytic
      behavior of shibire mutants at 27  degrees C. Electrophysiological work in NMJs
      of Ppt1-deficient larvae has revealed an increase in miniature excitatory
      junctional potentials (EJPs) and a significant depression of evoked EJPs in
      response to repetitive (10 hz) stimulation. Endocytosis was further examined in
      Ppt1-mutant larvae using FM1-43 uptake assays, demonstrating a significant
      decrease in FM1-43 uptake at the mutant NMJs. Finally, Ppt1-deficient and Ppt1
      point mutant larvae display defects in locomotion that are consistent with
      alterations in synaptic function. Taken together, our genetic, cellular, and
      electrophysiological analyses suggest a direct role for Ppt1 in synaptic vesicle
      exo- and endocytosis at motor nerve terminals of the Drosophila NMJ. 

PMID- 24091422
TI  - Bibliographic review of research publications on access to and use of medicines
      in low-income and middle-income countries in the Eastern Mediterranean Region:
      identifying the research gaps.
AB  - OBJECTIVES: We assessed the situation of academic publications on access to and
      use of medicines (ATM) in low-income and middle-income countries (LMICs) of the
      Eastern Mediterranean Region (EMR). We aimed to inform priority setting for
      research on ATM in the region. DESIGN: Bibliographic review of published studies.
      SETTING: LMICs in EMR. INCLUSION CRITERIA: Publications on ATM issues originating
      from or focusing on EMR LMICs covering the period 2000-2011. Publications
      involving multinational studies were included if at least one eligible country
      had been included in the study. INFORMATION SOURCES AND DATA EXTRACTION: We
      conducted comprehensive searches of the PubMed, Social Science Citation Index and
      Science Citation Index. We used the WHO ATM framework for data extraction and
      synthesis. We analysed the data according to the ATM issues, health system
      levels, year of publication and the countries of origin or focus of the studies.
      RESULTS: 151 articles met the inclusion criteria. Most articles (77%) originated
      from LMICs in EMR, suggesting that the majority of evidence on ATM in the region
      is home-grown. Over 60% of articles were from Iran, Pakistan, Jordan and Lebanon
      (in order of volume), while we found no studies assessing ATM in Somalia,
      Djibouti and South Sudan, all low-income countries. Most studies focused on the
      rational use of medicines, while affordability and financing received limited
      attention. There was a steady growth over time in the number of ATM publications
      in the region (r=0.87). CONCLUSIONS: There is a growing trend, over the years, of
      more studies from the region appearing in international journals. There is a need
      for further research on the financing and affordability aspects of ATM in the
      region. Cross-border issues and the roles of non-health sectors in access to
      medicines in the region have not been explored widely.

PMID- 24091423
TI  - A pragmatic randomised controlled trial of 'PhysioDirect' telephone assessment
      and advice services for patients with musculoskeletal problems: economic
      evaluation.
AB  - OBJECTIVES: To compare the cost-effectiveness of PhysioDirect with usual
      physiotherapy care for patients with musculoskeletal problems. DESIGN: (1) Cost
      consequences comparing cost to the National Health Service (NHS), to patients,
      and the value of lost productivity with a range of outcomes. (2) Cost-utility
      analysis comparing cost to the NHS with Quality-Adjusted Life Years (QALYs).
      SETTING: Four physiotherapy services in England. PARTICIPANTS: Adults (18+)
      referred by their general practitioner or self-referred for physiotherapy.
      INTERVENTIONS: PhysioDirect involved telephone assessment and advice followed by
      face-to-face care if needed. Usual care patients were placed on a waiting list
      for face-to-face care. PRIMARY AND SECONDARY OUTCOMES: Primary clinical outcome:
      physical component summary from the SF-36v2 at 6 months. Also included in the
      cost-consequences: Measure Yourself Medical Outcomes Profile; a Global
      Improvement Score; response to treatment; patient satisfaction; waiting time.
      Outcome for the cost-utility analysis: QALYs. RESULTS: 2249 patients took part
      (1506 PhysioDirect; 743 usual care). (1) Cost-consequences: there was no evidence
      of a difference between the two groups in the cost of physiotherapy, other NHS
      services, personal costs or value of time off work. Outcomes were also similar.
      (2) Cost-utility analysis based on complete cases (n=1272). Total NHS costs,
      including the cost of physiotherapy were higher in the PhysioDirect group by
      L19.30 (95% CI -L37.60 to L76.19) and there was a QALY gain of 0.007 (95% CI 
      0.003 to 0.016). The incremental cost-effectiveness ratio was L2889 and the net
      monetary benefit at lambda=L20 000 was L117 (95% CI -L86 to L310). CONCLUSIONS:
      PhysioDirect may be a cost-effective alternative to usual physiotherapy care,
      though only with careful management of staff time. Physiotherapists providing the
      service must be more fully occupied than was possible under trial conditions:
      consideration should be given to the scale of operation, opening times of the
      service and flexibility in the methods used to contact patients.

PMID- 24091424
TI  - Asthma and risk of non-respiratory tract infection: a population-based case
      control study.
AB  - OBJECTIVES: Asthmatics have increased risks of airway-related infections. Little
      is known about whether this is true for non-airway-related serious infections
      such as Escherichia coli bloodstream infection (BSI). We assessed whether asthma
      is associated with a risk of developing community-acquired E coli BSI. DESIGN:
      The study was designed as a population-based retrospective case-control study.
      SETTING: This population-based study was conducted in Olmsted County, Minnesota.
      PARTICIPANTS: The study included 259 all eligible community-acquired E coli BSI
      cases in Olmsted County, MN between 1998 and 2007 and 259 birthday-matched,
      gender-matched and residency-matched controls. PRIMARY AND SECONDARY OUTCOME
      MEASURES: Only community-acquired E coli BSI cases as the primary outcome was
      included. Asthma status as an exposure was ascertained by predetermined criteria.
      An adjusted OR and 95% CI for the association between asthma and risk of
      community-acquired E coli BSI was calculated using conditional logistic
      regression. RESULTS: Of 259 eligible cases, 179 (69%) were women and mean age was
      61+/-22 years. Of the 259 cases 37 (14%) and 16 (6%) of 259 controls had a prior
      history of asthma (adjusted OR 2.74; 95% CI 1.11 to 6.76; p=0.029). The
      population attributable risk of asthma for community-acquired E coli BSI was 9%.
      Although not statistically significant, there was a borderline association
      between having a history of food allergy and increased risk of community-acquired
      E coli BSI (6% vs 2%; adjusted OR 3.51; 95% CI 0.94 to 13.11; p=0.062).
      CONCLUSIONS: Based on the findings of the current population-based, case-control
      investigation, a history of asthma may be associated with risk of community
      acquired E coli BSI. The impact of asthma on risk of microbial infections may go
      beyond airways.

PMID- 24091425
TI  - Airway management and perioperative concerns in acromegaly patients undergoing
      endoscopic transsphenoidal surgery for pituitary tumors.
AB  - OBJECTIVES: Patients with acromegaly present unique challenges to cranial base
      surgery and anesthesia teams in the perioperative period, especially with regard
      to airway management. Abnormal airway anatomy may result from soft tissue
      hypertrophy and bony alterations. Additional perioperative challenges relate to
      the management of medical comorbidities. We aim to review perioperative airway
      concerns in acromegalic patients for the skull base surgeon in order to reduce
      preventable perioperative complications. STUDY DESIGN: Case series with chart
      review. SETTING: Tertiary care academic institution. SUBJECTS: Thirty-two
      acromegaly patients undergoing endoscopic transsphenoidal pituitary surgery.
      RESULTS: Videoscopic direct laryngoscopy intubation was required in 7 of 32
      patients (21.9%) and fiberoptic intubation in 4 of 32 patients (12.5%). Overall
      failure rate for first intubation technique used was 12.5% (4/32). Cardiovascular
      comorbidities (hypertension and conduction abnormalities predominated) were
      present in 16 of 32 patients (50%), and obstructive sleep apnea, or other
      respiratory conditions, existed in 12 of 32 patients (37.5%). CONCLUSIONS:
      Acromegaly patients present a particular challenge to the endoscopic skull base
      surgeon. Despite preoperative anesthesia and otolaryngology evaluation, many of
      these patients will experience an unanticipated airway challenge during
      intubation. Preoperative preparation and perioperative awareness of anatomic and
      physiologic abnormalities of acromegalic patients is essential for successful
      endoscopic surgery in this unique population.

PMID- 24091426
TI  - Trends in demographics, charges, and outcomes of patients undergoing excision of
      sporadic vestibular schwannoma.
AB  - OBJECTIVE: To assess demographics, charges, and outcome measures by temporal and
      volume analysis in the treatment of vestibular schwannoma. DESIGN: Cross
      sectional analysis. SETTING, SUBJECTS, AND METHODS: The California Hospital
      Inpatient Discharge Databases from 1996 to 2010. RESULTS: A total of 6545 cases
      from 1996 to 2010 were identified. Of these, 86.2% occurred at high-volume
      centers (HVCs), and the number of annual cases decreased by 28.5%. Patients
      presenting for surgery were increasingly younger, non-Caucasian, and likely to
      have comorbidities. Total charges significantly increased over time (P < .001),
      with the median total charge in 2006-2010 being $91,338 compared with $38,607.92
      in 1996-2000 after adjusting for inflation. Routine discharges (home or
      residence) were more likely at HVCs (odds ratio [OR] 5.48, P < .001) and less
      likely if patients had Medicaid (Medi-Cal; OR 0.51, P = .002) or Medicare (OR
      0.55, P = .022), were 65 years or older (OR 0.56, P = .025), or had comorbidities
      (OR 0.54, P < .001). Shorter hospital stays were more likely at HVCs (OR 3.77, P
      < .001) and less likely if patients had Medicaid (OR 0.36, P < .001) or
      comorbidities (OR 0.61, P < .001). Lesser total charges were more likely at HVCs
      (OR 2.12, P = .002) and less likely if patients had comorbidities (OR 0.70, P <
      .001). Mortality was less likely at HVCs (OR 0.10, P = .011). CONCLUSION: The
      profile of patients undergoing vestibular neuroma excision is changing. Surgical
      volume is decreasing, suggesting a trend toward more conservative management or
      stereotactic radiation. Patients are best served at HVCs, where routine
      discharges, shorter length of stay, decreased mortality, and lower total charges
      are more likely.

PMID- 24091427
TI  - Moose body mass variation revisited: disentangling effects of environmental
      conditions and genetics.
AB  - Large-scale geographical variation in phenotypic traits within species is often
      correlated to local environmental conditions and population density. Such
      phenotypic variation has recently been shown to also be influenced by genetic
      structuring of populations. In ungulates, large-scale geographical variation in
      phenotypic traits, such as body mass, has been related to environmental
      conditions and population density, but little is known about the genetic
      influences. Research on the genetic structure of moose suggests two distinct
      genetic lineages in Norway, structured along a north-south gradient. This
      corresponds with many environmental gradients, thus genetic structuring provides
      an additional factor affecting geographical phenotypic variation in Norwegian
      moose. We investigated if genetic structure explained geographical variation in
      body mass in Norwegian moose while accounting for environmental conditions, age
      and sex, and if it captured some of the variance in body mass that previously was
      attributed to environmental factors. Genetic structuring of moose was the most
      important variable in explaining the geographic variation in body mass within age
      and sex classes. Several environmental variables also had strong explanatory
      power, related to habitat diversity, environmental seasonality and winter
      harshness. The results suggest that environmental conditions, landscape
      characteristics, and genetic structure should be evaluated together when
      explaining large-scale patterns in phenotypic characters or life history traits.
      However, to better understand the role of genetic and environmental effects on
      phenotypic traits in moose, an extended individual-based study of variation in
      fitness-related characters is needed, preferably in an area of convergence
      between different genetic lineages. 

PMID- 24091428
TI  - Poly(acrylic acid)-block-poly(vinyl alcohol) anchored maghemite nanoparticles
      designed for multi-stimuli triggered drug release.
AB  - Original core/corona nanoparticles composed of a maghemite core and a stimuli
      responsive polymer coating made of poly(acrylic acid)-block-poly(vinyl alcohol)
      macromolecules were fabricated for drug delivery system (DDS) application. This
      kind of DDS aims to combine the advantage of stimuli-responsive polymer coating,
      in order to regulate the drug release behaviours under different conditions and
      furthermore, improve the biocompatibility and in vivo circulation half-time of
      the maghemite nanoparticles. Drug loading capacity was evaluated with methylene
      blue (MB), a cationic model drug. The triggered release of MB was studied under
      various stimuli such as pH, ionic strength and temperature. Local heating
      generated under alternating magnetic field (AMF) application was studied, and
      remotely AMF-triggered release was also confirmed, while a mild heating-up of the
      release medium was observed. Furthermore, their potential application as magnetic
      resonance imaging (MRI) contrast agents was explored via relaxivity measurements
      and acquisition of T2-weighted images. Preliminary studies on the cytotoxicity
      against mouse fibroblast-like L929 cell line and also their cellular uptake
      within human melanoma MEL-5 cell line were carried out. In conclusion, this kind
      of stimuli-responsive nanoparticles appears to be promising carriers for
      delivering drugs to some tumour sites or into cellular compartments with an
      acidic environment. 

PMID- 24091429
TI  - Selection of boron reagents for Suzuki-Miyaura coupling.
AB  - Suzuki-Miyaura (SM) cross-coupling is arguably the most widely-applied transition
      metal catalysed carbon-carbon bond forming reaction to date. Its success
      originates from a combination of exceptionally mild and functional group tolerant
      reaction conditions, with a relatively stable, readily prepared and generally
      environmentally benign organoboron reagent. A variety of such reagents have been
      developed for the process, with properties that have been tailored for
      application under specific SM coupling conditions. This review analyses the seven
      main classes of boron reagent that have been developed. The general physical and
      chemical properties of each class of reagent are evaluated with special emphasis
      on the currently understood mechanisms of transmetalation. The methods to prepare
      each reagent are outlined, followed by example applications in SM coupling. 

PMID- 24091430
TI  - Critical care management of patients with acute spinal cord injury.
AB  - Spinal cord injury (SCI) inevitably extends beyond neurologic consequences. The
      relationship between the spinal cord and its control of other organ systems make
      SCI management complex, requiring treatment on a multisystem approach. Patients
      frequently have hemodynamic instability and respiratory insufficiency secondary
      to the neurologic insult. Rigorous monitoring and anticipation of potential
      complications are essential in managing SCI, requiring a level of care provided
      in a neurocritical care unit. This review covers the pathophysiology, initial
      assessment, and stabilization in addition to acute management of cardiovascular
      and respiratory issues following SCI. Subsequent potential complications of deep
      vein thrombosis, gastrointestinal, and urinary systems and their management in
      the critical care setting are also addressed in this review. 

PMID- 24091431
TI  - Reduction of ventilator-associated pneumonia in the Neuroscience Intensive Care
      Unit: a multimodality prevention and testing protocol.
AB  - AIM: Ventilator-associated pneumonia (VAP) is a serious concern for patients in
      the Neuroscience Intensive Care Unit (NSICU). The risks to patients are
      significant and the monetary costs are astronomical. We review a multimodality
      approach that substantially reduced VAP rate in our ICU METHODS: Data from all
      patients admitted to the NSICU between January 2005 and April 2010 were reviewed.
      All ventilated patients were treated according to a multimodality VAP assessment
      and prevention protocol, implementation of which began in August of 2008 and was
      completed by March 2009. Rates of VAP before, during, and after implementation of
      the protocol are compared. VAP rates are also compared to national rates as
      obtained from the National Healthcare Safety Network (NHSN). RESULTS: In the pre
      implementation period, the VAP rate was 11.6 per 1000 ventilator days. This rate
      was twice the national average. In the post implementation period, the VAP rate
      was 5.5/1000 ventilator days. VAP rate dropped precipitously after full
      compliance with the protocol was achieved. CONCLUSION: Although intubated
      patients in the NSICU are at high risk for VAP, a significant reduction in VAP
      related morbidity and monetary costs can be obtained with multimodality
      prevention and testing protocols.

PMID- 24091432
TI  - Percutaneous arthrodesis of sacro-iliac joint: a pilot study.
AB  - AIM: Between 15-30% of patients presenting with low back pain have some SI joint
      involvement. The diagnosis of SI joint involvement in low back pain is quite
      difficult and depends on a detailed combination of clinical manoeuvres and
      injection tests. In 5% of patients with SI joint pain, the joint is physically
      unstable (termed disruption) resulting in ineffective medical and conservative
      therapeutic options. In this study we present the results of the first 12 cases
      of SI joint disruption treated using a minimally invasive SI joint arthrodesis
      system in order to evaluate the safety and the efficacy of this system. METHODS:
      Medical charts at a single center were reviewed for demographics, perioperative
      metrics, patient reported outcomes for pain, function and quality of life (NRS,
      ODI and RDQ respectively), as well as satisfaction with surgery (yes/no) and
      results of postoperative CT scan. RESULTS: Mean age was 53 years (range 36-71)
      and all patients were female. Patient reported outcomes at follow up (range 8-18
      months) improved clinically as well as statistically as evidenced by a mean
      improvement in pain on NRS of 4 points, back related function on ODI by 19.4
      points, and in quality of life measured using RDQ of 13.6 points (all P=0.01).
      Local hematoma requiring drainage was apparent in 2 patients. Patient
      satisfaction was 100%. All 3 month CT scans showed initial fusion. CONCLUSION:
      The results of this study confirm that MIS SI joint fusion using the iFuse
      Implant System is safe and effective method of treating patients with SI joint
      disruption.

PMID- 24091433
TI  - The proposal of subgroups for grade V on World Federation of Neurologic Surgeons
      grading for subarachnoid hemorrhage.
AB  - AIM: Some of cases suffering from subarachnoid hemorrhages (SAHs) in grade V on
      World Federation of Neurologic Surgeons (WFNS) grading can gain a good prognosis.
      The outcome of patients of SAH in grade V on WFNS grading in their institute was
      here investigated. METHODS: Between April 2007 and July 2012, consecutive 37
      patients had SAH diagnosed on CT scan and were classified in grade V on WFNS
      grading in Kosei General Hospital. There were seventeen male and twenty female
      patients. We were assigned to patients with spontaneous respiration and without
      oculomotor palsy (N group, N.=11), and patients with oculomotor palsy (O group,
      N.=26). Patients were evaluated by mRS. RESULTS: The prognosis in N group was
      significantly better than in O group (P<0.001). CONCLUSION: Surgical treatments
      should be considered for SAH patients without oculomotor palsy. It is necessary
      to make subgroups in grade V on WFNS grading in order to decide operative
      indication and evaluate the treatment results of SAH in grade V.

PMID- 24091434
TI  - Effect of degeneration on gene expression of chondrogenic and inflammatory marker
      genes of intervertebral disc cells: a preliminary study.
AB  - AIM: New techniques for biological repair in the treatment of degenerative disc
      disease (DDD) have been developed recently. The question arises whether it is
      possible to find a predictive marker to identify a patient population which could
      benefit from this new treatment option. Standard magnetic resonance imaging (MRI)
      fails to differentiate between pathologic painful and asymptomatic aging discs.
      Neurological symptoms contribute to identifying the pathological level. In this
      preliminary translational research study we analysed the gene expression of
      structure proteins and inflammatory mediators as well as histological features of
      lumbar intervertebral discs in symptomatic patients with various signs of
      degeneration in the MRI. METHODS: Specimens of intervertebral disc tissue were
      obtained from 20 patients undergoing lumbar nucleotomy. Preoperatively, a group
      selection based on four pre-defined MRI-criteria was performed: Group 1 (mild
      signs of degeneration), group 2 (moderate), group 3 (moderate-severe), group 4
      (severe). RESULTS: An increase of the expression of structural proteins and
      inflammatory markers could be observed in MRI-groups 2 and 3. Gene expression of
      collagen type I and II and aggrecan went along with levels of cyclooxygenase-2
      (COX-2) and (fibroblast growth factor-2) FGF-2 expression. Histological
      examination showed signs of granulation tissue in only 35% of cases, but no
      differences between the groups. CONCLUSION: Our findings implicate that the gene
      expression of structural proteins might correlate with the appearance of
      inflammatory mediators in symptomatic patients with moderate disc changes in the
      MRI in this preliminary clinical subset. The assessment of cell activity and
      protein expression in a larger number of patients could be next step to support
      and supplement the present data.

PMID- 24091435
TI  - Application of transport phenomena analysis technique to cerebrospinal fluid.
AB  - The study of hydrocephalus and the modeling of cerebrospinal fluid flow have
      proceeded in the past using mathematical analysis that was very capable of
      prediction phenomenonologically but not well in physiologic parameters. In this
      paper, the basis of fluid dynamics at the physiologic state is explained using
      first established equations of transport phenomenon. Then, microscopic and
      molecular level techniques of modeling are described using porous media theory
      and chemical kinetic theory and then applied to cerebrospinal fluid (CSF)
      dynamics. Using techniques of transport analysis allows the field of
      cerebrospinal fluid dynamics to approach the level of sophistication of urine and
      blood transport. Concepts such as intracellular and intercellular pathways,
      compartmentalization, and tortuosity are associated with quantifiable parameters
      that are relevant to the anatomy and physiology of cerebrospinal fluid transport.
      The engineering field of transport phenomenon is rich and steeped in
      architectural, aeronautical, nautical, and more recently biological history. This
      paper summarizes and reviews the approaches that have been taken in the field of
      engineering and applies it to CSF flow. 

PMID- 24091436
TI  - Evidence-based review and guidelines for the management of myxopapillary and
      intramedullary ependymoma.

PMID- 24091438
TI  - Effects of blood purification therapy on a patient with ifosfamide-induced
      neurotoxicity and acute kidney injury.
AB  - Ifosfamide combined with other antineoplastic agents has been effective in the
      treatment of osteosarcoma, although adverse effects are reported in the
      increasing use of ifosfamide. The most serious complications among the ifosfamide
      intoxications are neurotoxicity and nephrotoxicity. We report on a patient who
      suffered from ifosfamide-induced neurotoxicity and nephrotoxicity and
      rhabdomyolysis after chemotherapy, and was successfully treated with blood
      purification therapy. The patient had osteosarcoma with multiple lung metastases,
      wherein the chemotherapy included ifosfamide (3 g/m(2)) and VP-16 (60 mg/m(2))
      per day for 3 days. The first day after chemotherapy, the patient experienced
      impaired consciousness and renal function. Based on the clinical course and
      laboratory data, the diagnosis was ifosfamide-induced neurotoxicity and the acute
      kidney injury caused by ifosfamide-induced nephrotoxicity and rhabdomyolysis. As
      a detoxification treatment, blood purification procedures were performed daily
      for 3 days. Thirty-six hours after the first hemodialysis session, the symptoms
      of neurotoxicity disappeared. In the lead-up to the 10th day following
      intoxication, the serum creatinine recovered to the baseline level. Serum
      ifosfamide concentration decreased from 41.9 to 12.1 ng/ml by the second session
      of blood purification. Despite the absence of an established detoxification
      method when complications present simultaneously, blood purification therapy
      should be considered for treating severe concurrent neurotoxicity and
      nephrotoxicity and rhabdomyolysis.

PMID- 24091439
TI  - Differential proteomic analysis of caveolin-1 KO cells reveals Sh2b3 and Clec12b
      as novel interaction partners of caveolin-1 and Capns1 as a potential mediator of
      caveolin-1-induced apoptosis.
AB  - Caveolin-1 (Cav1) is a small scaffolding protein involved in a variety of
      cellular functions, including cell signaling, lipid transport and membrane
      traffic. The objective of this study was to use comparative proteomics to
      identify differentially expressed proteins in Cav1 knockout (KO) mouse embryonic
      fibroblasts. These deregulated proteins were then analyzed using systems biology
      tools to gain insight into the local network properties and to identify the
      interaction partners of Cav1. We identified five proteins that were up-regulated
      and ten proteins that were down-regulated in Cav1 KO cells, suggesting that the
      local network behaves as a complex system. Protein interaction network analysis
      revealed two proteins, Sh2b3 and Clec12b, as novel interaction partners of Cav1.
      Functional annotation showed apoptosis signaling as the most significant pathway.
      To validate this functional annotation, Cav1 KO cells showed more than 1.5-fold
      increase in caspase-3 activity over wild type cells upon apoptotic stimulation.
      We also found that calpain small subunit 1 is up-regulated in Cav1 KO cells and
      directly influences the cell response to apoptotic stimuli. Moreover, Capns1 was
      reduced in Cav1 KO cells following re-expression of Cav1, and suppression of
      Capns1 expression in Cav1 KO cells significantly inhibited the cells to apoptotic
      stimuli, as measured by caspase 3 activity. In conclusion, our results suggest
      that Sh2b3 and Clec12b functionally interact with Cav1 and that calpain small
      subunit 1 may mediate Cav1-induced apoptosis. 

PMID- 24091440
TI  - Predicting carotid plaque characteristics using quantitative color-coded T1
      weighted MR plaque imaging: correlation with carotid endarterectomy specimens.
AB  - BACKGROUND AND PURPOSE: MR plaque imaging is used to evaluate the risk of embolic
      complications during carotid endarterectomy and carotid artery stent placement.
      However, its performance for characterizing intraplaque components has varied
      across studies and is generally suboptimal. Hence, we correlated MR imaging
      results with histologic findings to determine whether a combination of high
      contrast T1-weighted imaging and quantitative image analysis could readily
      determine plaque characteristics. MATERIALS AND METHODS: We prospectively
      examined 40 consecutive patients before carotid endarterectomy by using a 1.5T
      scanner and axial T1-weighted spin-echo images under optimized scanning
      conditions. The percentage areas of intraplaque fibrous tissue, lipid/necrosis,
      and hemorrhage were calculated automatically by using the software with
      previously reported cutoff values and were compared with those of the specimens.
      The thickness of the fibrous cap was also measured manually. RESULTS: The
      percentage areas of fibrous, lipid/necrotic, and hemorrhagic components were 5.7%
      98.7%, 1.3%-65.7%, and 0%-82.0%, respectively, as determined by the MR images,
      whereas the corresponding values were 4.8%-92.3%, 7.0%-93.8%, and 0%-70.4%,
      respectively, as determined by histologic examination. Significant positive
      correlation and agreement were observed between MR images and histologic
      specimens (r = 0.92, 0.79, and 0.92; intraclass correlation coefficients = 0.91,
      0.67, and 0.89; respectively). Thickness of the fibrous caps on MR images (0.21
      0.87 mm) and in the specimens (0.14-0.83 mm) also showed positive correlation and
      agreement (r = 0.61, intraclass correlation coefficient = 0.59). CONCLUSIONS:
      Quantitative analysis of high-contrast T1-weighted images can accurately evaluate
      the composition of carotid plaques in carotid endarterectomy candidates.

PMID- 24091441
TI  - The outcome and efficacy of recanalization in patients with acute internal
      carotid artery occlusion.
AB  - BACKGROUND AND PURPOSE: Acute occlusion of the ICA is often associated with poor
      outcomes and severe neurologic deficits. This study was conducted to evaluate
      outcome of the occluded ICA and efficacy of recanalization under protective flow
      arrest. MATERIALS AND METHODS: Fifty consecutive patients who underwent
      endovascular treatment for acute ICA occlusion were identified from the
      prospectively collected data base. We assessed NIHSSo, occlusion type
      (cardioembolism vs atherosclerosis), occlusion level (supraclinoid-terminal,
      petrocavernous, or bulb-cervical), recanalization degree (TICI), and efficacy of
      recanalization (protective flow arrest vs nonprotection) leading to better
      outcome. RESULTS: Successful recanalization (TICI >= 2) was obtained in 90% of
      patients and good recovery (mRS <= 2) in 60% of patients. Good outcome was
      related to National Institutes of Health Stroke Scale score on admission (P <
      .001), TICI (P < .007), occlusion type (P = .022), and occlusion level (P =
      .038). Poor initial patient status, less recanalization, cardioembolism, and
      supraclinoid-terminal occlusion were associated with poor prognosis. Application
      of protective flow arrest led to better outcome in the distal ICA segment than in
      the bulb-cervical segment. CONCLUSIONS: In addition to the initial patient status
      and successful recanalization, the occlusion level or type of the occluded ICA
      could affect clinical outcome. In this study, treatment benefits of protective
      flow arrest were accentuated in patients with ICA occlusion above the bulb
      cervical segment.

PMID- 24091442
TI  - The complicated equation of smell, flavor, and taste.

PMID- 24091443
TI  - Spontaneous lateral sphenoid cephaloceles: anatomic factors contributing to
      pathogenesis and proposed classification.
AB  - SUMMARY: Spontaneous lateral sphenoid cephaloceles arise from bony defects in the
      lateral sphenoid, in the absence of predisposing factors such as trauma, surgery,
      mass, or congenital skull base malformation. We reviewed CT and MR imaging
      findings and clinical data of 26 patients with spontaneous lateral sphenoid
      cephaloceles to better understand anatomic contributions to pathogenesis, varying
      clinical and imaging manifestations, and descriptive terminology. Two types of
      spontaneous lateral sphenoid cephaloceles were identified. In 15 of 26 patients,
      a type 1 spontaneous lateral sphenoid cephalocele was noted, herniating into a
      pneumatized lateral recess of the sphenoid sinus, and typically presenting with
      CSF leak and/or headache. In 11 of 26 patients, a type 2 spontaneous lateral
      sphenoid cephalocele was noted, isolated to the greater sphenoid wing without
      extension into the sphenoid sinus, presenting with seizures, headaches,
      meningitis, cranial neuropathy, or detected incidentally. All patients had
      sphenoid arachnoid pits, and 61% of patients had an empty or partially empty
      sella, suggesting that altered CSF dynamics may play a role in their genesis.

PMID- 24091444
TI  - Regional cerebral blood flow in children from 3 to 5 months of age.
AB  - BACKGROUND AND PURPOSE: Understanding the relationship between brain and behavior
      in early childhood requires a probe of functional brain development. We report
      the first large study of regional CBF by use of arterial spin-labeling in young
      children. MATERIALS AND METHODS: Cerebral blood flow by use of arterial spin
      labeling was measured in 61 healthy children between the ages of 3 and 5 months.
      Blood flow maps were parcellated into 8 broadly defined anatomic regions of each
      cerebral hemisphere. RESULTS: There was no sex effect; however, group analysis
      demonstrated significantly greater CBF in the sensorimotor and occipital regions
      compared with dorsolateral prefrontal, subgenual, and orbitofrontal areas (P <
      .0001). A significant age effect was also identified, with the largest increase
      in blood flow between 3 and 5 months occurring in the following regions:
      orbitofrontal (P < .009), subgenual (P < .002), and inferior occipital lobe (P =
      .001). CONCLUSIONS: These results are consistent with prior histologic studies
      demonstrating regional variation in brain maturation and suggest that arterial
      spin-labeling is sensitive to regional as well as age-related differences in CBF
      in young children.

PMID- 24091445
TI  - Shoulder apprehension impacts large-scale functional brain networks.
AB  - BACKROUND AND PURPOSE: Shoulder apprehension is defined as anxiety and resistance
      in patients with a history of anterior glenohumeral instability. It remains
      unclear whether shoulder apprehension is the result of true recurrent instability
      or a memorized subjective sensation. We tested whether visual presentation of
      apprehension videos modifies functional brain networks associated with motor
      resistance and anxiety. MATERIALS AND METHODS: This prospective study includes 15
      consecutive right-handed male patients with shoulder apprehension (9 with right
      shoulder apprehension, 6 with left shoulder apprehension; 27.5 +/- 6.4 years) and
      10 healthy male right-handed age-matched control participants (29.0 +/- 4.7
      years). Multimodal MR imaging included 1) functional connectivity tensorial
      independent component analysis, 2) task-related general linear model analysis
      during visual stimulation of movies showing typical apprehension movements vs
      control videos, 3) voxel-based morphometry analysis of GM, and 4) tract-based
      spatial statistics analysis of WM. RESULTS: Patients with shoulder apprehension
      had significant (P < .05 corrected) increase in task-correlated functional
      connectivity, notably in the bilateral primary sensory-motor area and
      dorsolateral prefrontal cortex and, to a lesser degree, the bilateral dorsomedial
      prefrontal cortex, anterior insula, and dorsal anterior cingulate cortex (+148%
      right, +144% left). Anticorrelated functional connectivity decreased in the
      higher-level visual and parietal areas (-185%). There were no potentially
      confounding structural changes in GM or WM. CONCLUSIONS: Shoulder apprehension
      induces specific reorganization in apprehension-related functional connectivity
      of the primary sensory-motor areas (motor resistance), dorsolateral prefrontal
      cortex (cognitive control of motor behavior), and the dorsal anterior cingulate
      cortex/dorsomedial prefrontal cortex and anterior insula (anxiety and emotional
      regulation).

PMID- 24091446
TI  - It's all about data.

PMID- 24091447
TI  - Reply to 'Dissipative feedback does not improve the optimal resolution of
      incoherent force detection'.

PMID- 24091448
TI  - Report the awful truth!

PMID- 24091449
TI  - Anti-nanotech violence.

PMID- 24091451
TI  - Nanocrystals: Shining a light on upconversion.

PMID- 24091452
TI  - DNA computing: Molecules reach consensus.

PMID- 24091453
TI  - Spintronics: an insulator-based transistor.

PMID- 24091456
TI  - Numerical modeling of the wind flow over a transverse dune.
AB  - Transverse dunes, which form under unidirectional winds and have fixed profile in
      the direction perpendicular to the wind, occur on all celestial objects of our
      solar system where dunes have been detected. Here we perform a numerical study of
      the average turbulent wind flow over a transverse dune by means of computational
      fluid dynamics simulations. We find that the length of the zone of recirculating
      flow at the dune lee - the separation bubble - displays a surprisingly strong
      dependence on the wind shear velocity, u: it is nearly independent of u for shear
      velocities within the range between 0.2 m/s and 0.8 m/s but increases linearly
      with u for larger shear velocities. Our calculations show that transport in the
      direction opposite to dune migration within the separation bubble can be
      sustained if u is larger than approximately 0.39 m/s, whereas a larger value of u
      (about 0.49 m/s) is required to initiate this reverse transport.

PMID- 24091457
TI  - Complete regression of primary epicardial leiomyosarcoma with single agent
      doxorubicin in an elderly patient.

PMID- 24091458
TI  - [Spinal cord stimulation revisited].

PMID- 24091454
TI  - Micro- and nanoscale devices for the investigation of epigenetics and chromatin
      dynamics.
AB  - Deoxyribonucleic acid (DNA) is the blueprint on which life is based and
      transmitted, but the way in which chromatin - a dynamic complex of nucleic acids
      and proteins - is packaged and behaves in the cellular nucleus has only begun to
      be investigated. Epigenetic modifications sit 'on top of' the genome and affect
      how DNA is compacted into chromatin and transcribed into ribonucleic acid (RNA).
      The packaging and modifications around the genome have been shown to exert
      significant influence on cellular behaviour and, in turn, human development and
      disease. However, conventional techniques for studying epigenetic or
      conformational modifications of chromosomes have inherent limitations and,
      therefore, new methods based on micro- and nanoscale devices have been sought.
      Here, we review the development of these devices and explore their use in the
      study of DNA modifications, chromatin modifications and higher-order chromatin
      structures. 

PMID- 24091459
TI  - [Factors which affect the neurological condition in subarachnoid hemorrhage].
AB  - The factors which were related to the neurological condition were analyzed in 233
      cases of subarachnoid hemorrhage. Bivariate analysis and
      multiple(binomial)logistic regression analysis were performed as for Hunt &
      Kosnik grade, modified Rankin Scale at discharge and modified Rankin Scale in the
      out-patient department to detect the factors which were related to the
      neurological condition. Hematoma-filled intraventricular hemorrhage,
      intracerebral hemorrhage with midline shift, acute subdural hematoma and aneurysm
      of the vertebrobasilar system were the representative factors which caused poor
      neurological condition. Hunt & Kosnik grade was poor when rebleeding occurred or
      hematoma was formed in the sylvian fissure. Hunt & Kosnik grade and modified
      Rankin Scale at discharge tended to be poor in the cases with acute
      hydrocephalus. The elevation of intracranial pressure was the major factor in
      neurological deterioration. 

PMID- 24091460
TI  - [A case of solitary fibrous tumor in the sella turcica].
AB  - A 64-year-old male presented with an incidental tumor in the sella turcica during
      a brain medical checkup. Because he lacked any neurological symptoms or signs of
      pituitary dysfunction, the patient did not undergo surgery. Three years later,
      visual disturbances developed, including poor eyesight and visual field defects.
      The response to the growth hormone(GH)releasing peptide-2 demonstrated severe GH
      deficiency. MRI revealed an enlarged tumor appearing as a mosaic pattern of high
      and very low intensity on T2-weighted imaging. The region of very low intensity
      on T2-weighted imaging exhibited enhancement after T1 gadolinium-DTPA
      administration. The tumor was totally removed via the microscopic trans
      sphenoidal approach in combination with endoscopic observation. The hard tumor
      adhered to the dura of the sella turcica and the medial wall of the left
      cavernous sinus. Histological verification confirmed a solitary fibrous
      tumor(SFT). Fourteen months after the operation, MRI revealed no recurrent
      tumors. SFT infrequently occurs in the sella turcica; however it should be
      included in the differential diagnosis in cases of enhanced tumors with marked
      low intensity on T2-weighted imaging.

PMID- 24091461
TI  - [Differential diagnosis of and therapy for anaplastic astroblastoma: case report
      and review of the literature].
AB  - Astroblastomas are rare glial tumors. We report a case of 33-year-old woman with
      high-grade astroblastoma with hypervascularity. She had a one-month history of
      right visual disturbance and papillar edema. MRI revealed a lobulated mass with
      cysts and flow voids in the right superficial frontal lobe, a phenomenon
      described as "bubbly appearance". Right carotid angiography demonstrated marked
      tumor stain and early venous filling. MR spectroscopy showed an increase in
      myoinositol and the choline/creatine ratio, and decreased N-acetyl aspartate. The
      lipid and lactate level was not increased. The well-circumscribed tumor was
      totally resected. Histological examination showed perivascular pseudorosettes and
      hyalinization of blood vessels with high cellularity, anaplastic nuclear
      features, focal necrosis, mitosis, and endothelial proliferation.
      Immunohistochemically, glial fibrillary acidic protein and S-100 protein were
      intensely positive and the MIB-1 labeling index was high(20%)in the tumor cells.
      Based on these findings, a diagnosis of high-grade astroblastoma was made. The
      patient received postoperative radiotherapy and chemotherapy with temozolomide
      and suffered no relapse in the course of 3 years after surgery.
      Characteristically, astroblastomas manifest a "bubbly appearance" and a lobulated
      mass on MRI scans. As these tumors tend to be hypervascular, angiograms are
      useful for designing the operative strategy. However, their low-or high grade is
      difficult to ascertain preoperatively based on MRI-, MRS-, and DSA findings. The
      standard therapy for high-grade astroblastoma is total resection and
      postoperative radiation therapy. As the incidence of tumor recurrence is high, we
      recommend additional chemotherapy with TMZ. 

PMID- 24091462
TI  - [A case of cavernous sinus aspergillosis].
AB  - We reported a case of cavernous sinus aspergillosis. A 62-year-old man complained
      of trigeminal neuralgia in the right V1 region. Neurological examination on
      admission showed ptosis, loss of light reflex and ophthalmoplegia externa in the
      right side. MRI enhanced with gadolinium demonstrated sphenoid sinusitis and mass
      lesion in the right cavernous sinus. MRA revealed right internal carotid artery
      occlusion. An open biopsy using the extradural temporopolar approach was
      performed. Pus discharge was observed from the cavernous sinus and histological
      examination showed hypha of Aspergillus. With early voriconazole treatment, the
      patient had improvement in headache, ptosis and ophthalmoplegia externa.
      Cavernous sinus aspergillosis is often found after sphenoiditis. It results in
      invasion to an internal carotid artery and worsens the patient's prognosis by
      cerebral infarction, so early diagnosis and treatment are important. We should
      consider aspergillosis as one of the differential diagnoses of a mass in the
      cavernous sinus. The epidural approach to this lesion was available to obviate
      aspergillus dissemination into the medullary cavity. 

PMID- 24091463
TI  - [Systematic review of complications for proper informed consent: (10)
      endovascular therapy for unruptured intracranial aneurysms].
AB  - Less invasive neuroimaging modalities have recently resulted in the more frequent
      detection of unruptured intracranial aneurysms(UIAs). Therefore, more patients,
      than ever before, with UIAs are currently being referred to neurosurgeons, who
      then must inform their patients of the optimal management possibilities.
      Endovascular therapy has become an important and well-known alternative to
      surgical clipping. However, as many neurosurgeons are not yet familiar enough
      with endovascular therapy, it is difficult for them to clearly explain the risks
      to their patients. The purpose of this systematic review is to disclose the risks
      of endovascular therapy for UIAs, which should be helpful to neurosurgeons, so
      that they can provide the appropriate information to their patients in order to
      obtain informed consent. In the present study, the overall morbidity and
      mortality rate of endovascular therapy of UIAs was 4.4% and 0.7%, respectively.
      Elderly patients had a higher risk of morbidity and mortality than did younger
      patients. The average risks of thromboembolic events and intraprocedural aneurysm
      rupture were 6.6% and 1.7%, respectively. Although posttreatment bleeding was
      extremely rare, patients with incompletely occluded large UIAs were more at risk.
      Furthermore, large UIAs more frequently required retreatment than did smaller
      ones. Other complications(e.g., puncture site complications, side effects due to
      the contrast medium, radiation injuries, heparin-induced thrombocytopenia,
      perianeurysmal edema, hydrocephalus, and aseptic meningitis)must also be
      explained to the patient. 

PMID- 24091464
TI  - [Required knowledge for spinal surgeon: (2) radiological diagnosis for spinal
      diseases].

PMID- 24091465
TI  - Abnormal small airways function in children with mild asthma.
AB  - BACKGROUND: Small airways disease is a hallmark in adults with persistent asthma,
      but little is known about small airways function in children with mild asthma and
      normal spirometry. We assessed ventilation heterogeneity, a marker of small
      airways function, with an easy tidal breath single-breath washout (SBW) technique
      in school-aged children with mild asthma and normal FEV1 and healthy age-matched
      control subjects. METHODS: The primary outcome was the double-tracer gas phase
      III slope (SDTG), an index of ventilation heterogeneity in acinar airways derived
      from the tidal double-tracer gas SBW test. The second outcome was the nitrogen
      phase III slope (SN2), an index of global ventilation heterogeneity derived from
      the tidal nitrogen SBW test using pure oxygen. Triplicate SBW and spirometry
      tests were performed in healthy children (n=35) and children with asthma (n=31)
      at baseline and in children with asthma after bronchodilation. RESULTS: Acinar
      (SDTG) but not global (SN2) ventilation heterogeneity was significantly increased
      in asthma despite normal FEV1. Of the 31 children with asthma, abnormal results
      were found for SDTG (<=-2 z scores) in 11; forced expiratory flow, midexpiratory
      phase (FEF25%-75%) in three; and FEV1 in zero. After bronchodilation, SDTG, SN2,
      FEF25%-75%, and FEV1 significantly changed (mean [95% CI] change from baseline,
      36% [15%-56%], 38% [18%-58%], 17% [9-25%], and 6% [3%-9%], respectively).
      CONCLUSIONS: Abnormal acinar ventilation heterogeneity in one-third of the
      children suggests that small airways disease may be present despite rare and mild
      asthma symptoms and normal spirometry. The easy tidal SBW technique has
      considerable potential as a clinical and research outcome in children with
      asthma.

PMID- 24091466
TI  - Low amplitude characterization tests conducted at regular intervals can affect
      tendon mechanobiological response.
AB  - In bioreactor studies of tissue mechanobiology, characterizing changes in tissue
      quality is essential for understanding and predicting the response to mechanical
      stimuli. Unfortunately, current methods are often destructive and cannot be used
      at regular intervals on the same sample to characterize progression over time.
      Non-destructive methods such as low amplitude stress relaxation tests could be
      used, but then, the following dilemma comes into play: how can we accurately
      measure live tissue progression over time if the tissue is reacting to our
      measurement methods? In this study, we investigated the hypothesis that stress
      relaxation tests at physiological amplitudes conducted at regular intervals
      between stimulation periods do not modify tissue progression over time. Live,
      healthy tendons were subjected to mechanical stimuli inside a bioreactor for 3
      days. The tendons were grouped based on the daily characterization protocol (24
      or 0 stress relaxation tests) and their progression over time were compared.
      Stress relaxation tests at physiological amplitudes modified the tendon response
      to mechanical stimulation as observed through mechanical and histologic analyses.
      Possible solutions to eliminate or minimize the effect of stress relaxation tests
      are to use the mechanical stimuli to characterize tissue progression or to limit
      the number of stress relaxation tests.

PMID- 24091467
TI  - Aromatic peptide amphiphiles: significance of the Fmoc moiety.
AB  - Aromatic peptide amphiphile hydrogelators commonly utilise the fluorenyl-9
      methoxycarbonyl moiety as an N-terminal capping group. Material properties and
      spectroscopic techniques show the influence of alternative linkers between the
      fluorenyl moiety and the peptide. This study establishes whether methoxycarbonyl
      is an optimal or mainly convenient linker, for this class of self-assembling
      systems. 

PMID- 24091468
TI  - Hybrid organic PVDF-inorganic M-rGO-TiO2 (M = Ag, Pt) nanocomposites for
      multifunctional volatile organic compound sensing and photocatalytic degradation
      H2 production.
AB  - This work focused on the development of a hybrid organic-inorganic TiO2
      nanocomposite, which demonstrates the first ever report on harmful volatile
      organic compound (VOC) sensing and photocatalytic degradation-H2 production. The
      sensing and photocatalytic properties are enhanced by the synergetic effects of
      well-structured TiO2 nanotubes, metal nanoparticles and reduced graphene oxide
      loading for enhanced light absorption and charge-transfer kinetics. Hybridization
      of a functionalized TiO2 nanocomposite with a polyvinylidene fluoride (PVDF)
      matrix induced strong cross-linking networks between the inorganic-organic
      components, which promote mechanical reinforcement-flexibility and highly porous
      asymmetric structures. The developed solution processable nanocomposite has
      immense potential to remedy the global environmental and energy issues by
      producing clean water/air and energy from organic compound waste. 

PMID- 24091469
TI  - Therapeutic horseback riding outcomes of parent-identified goals for children
      with autism spectrum disorder: an ABA' multiple case design examining dosing and
      generalization to the home and community.
AB  - We examined whether different doses of therapeutic riding influenced parent
      nominated target behaviors of children with autism spectrum disorder (ASD) (a)
      during the session (b) at home, and (c) in the community. We used a single
      subject multiple Baseline, multiple case design, with dosing of 1, 3, and 5
      times/week. Three boys with ASD, 6-8 years of age participated, and counts of
      target behaviors were collected in each setting and phase of the study. Compared
      to Baseline, 70% of the target behaviors were better during Intervention and
      improvement was retained in 63% of the behaviors during Withdrawal. Increased
      doses of therapeutic riding were significant for magnitude of change, and the
      effect of the therapeutic riding sessions generalized to home and community.

PMID- 24091470
TI  - The Mechanisms Underlying the ASD Advantage in Visual Search.
AB  - A number of studies have demonstrated that individuals with autism spectrum
      disorders (ASDs) are faster or more successful than typically developing control
      participants at various visual-attentional tasks (for reviews, see Dakin and
      Frith in Neuron 48:497-507, 2005; Simmons et al. in Vis Res 49:2705-2739, 2009).
      This "ASD advantage" was first identified in the domain of visual search by
      Plaisted et al. (J Child Psychol Psychiatry 39:777-783, 1998). Here we survey the
      findings of visual search studies from the past 15 years that contrasted the
      performance of individuals with and without ASD. Although there are some minor
      caveats, the overall consensus is that-across development and a broad range of
      symptom severity-individuals with ASD reliably outperform controls on visual
      search. The etiology of the ASD advantage has not been formally specified, but
      has been commonly attributed to 'enhanced perceptual discrimination', a superior
      ability to visually discriminate between targets and distractors in such tasks
      (e.g. O'Riordan in Cognition 77:81-96, 2000). As well, there is considerable
      evidence for impairments of the attentional network in ASD (for a review, see
      Keehn et al. in J Child Psychol Psychiatry 37:164-183, 2013). We discuss some
      recent results from our laboratory that support an attentional, rather than
      perceptual explanation for the ASD advantage in visual search. We speculate that
      this new conceptualization may offer a better understanding of some of the
      behavioral symptoms associated with ASD, such as over-focusing and restricted
      interests. 

PMID- 24091471
TI  - Self-reported Pleasantness Ratings and Examiner-Coded Defensiveness in Response
      to Touch in Children with ASD: Effects of Stimulus Material and Bodily Location.
AB  - Tactile defensiveness, characterized by behavioral hyperresponsiveness and
      negative emotional responses to touch, is a common manifestation of aberrant
      sensory processing in autism spectrum disorders (ASD) and other developmental
      disabilities (DD). Variations in tactile defensiveness with the properties of the
      stimulus and the bodily site of stimulation have been addressed in adults with
      self-report of perceived tactile pleasantness, but not in children. We presented
      three materials (pleasant, unpleasant, social) at three bodily sites and measured
      both examiner-coded defensiveness and self-reported pleasantness from a group of
      children with ASD and two comparison groups (one with DD, one with typical
      development (TD)). The main findings were: (1) children with ASD and DD showed
      significantly more defensiveness reactions and lower pleasantness ratings than
      the TD group, with higher variability, (2) there was a double dissociation for
      the effects of material and bodily site of stimulation: while bodily site
      predicted behavioral defensiveness, material predicted pleasantness rating.
      Additionally, it was noted that (3) the most pleasant material and the social
      touch conditions best distinguished ASD and DD from TD on defensiveness, and (4)
      within the ASD group, social impairment and defensiveness in bodily sites
      associated with social touch were positively correlated, suggesting a clinically
      relevant distinction between social and discriminative touch in ASD. 

PMID- 24091472
TI  - Development and evaluation of educational materials for pre-hospital and
      emergency department personnel on the care of patients with autism spectrum
      disorder.
AB  - With the rising prevalence of patients with autism spectrum disorder (ASD), there
      has been an increase in the acute presentation of these individuals to the
      general health care system. Emergency medical services and emergency department
      personnel commonly address the health care needs of patients with ASD at times of
      crisis. Unfortunately, there is little education provided to front-line emergency
      medical technicians, paramedics and emergency nurses on the characteristics of
      ASD and how these characteristics can create challenges for individuals with ASD
      and their health care providers in the pre-hospital and emergency department
      settings. This paper describes the development of educational materials on ASD
      and the results of training of emergency medical services and emergency
      department personnel. 

PMID- 24091474
TI  - The extended-spectrum AmpC genotype of Pseudomonas aeruginosa strains from Egypt:
      an underlying threat to anti-pseudomonal treatment options.

PMID- 24091473
TI  - Resuscitation with lipid, epinephrine, or both in levobupivacaine-induced cardiac
      toxicity in newborn piglets.
AB  - BACKGROUND: The optimal dosing regimens of lipid emulsion, epinephrine, or both
      are not yet determined in neonates in cases of local anaesthetic systemic
      toxicity (LAST). METHODS: Newborn piglets received levobupivacaine until
      cardiovascular collapse occurred. Standard cardiopulmonary resuscitation was
      started and electrocardiogram (ECG) was monitored for ventricular tachycardia,
      fibrillation, or QRS prolongation. Piglets were then randomly allocated to four
      groups: control (saline), Intralipid((r)) alone, epinephrine alone, or a
      combination of Intralipd plus epinephrine. Resuscitation continued for 30 min or
      until there was a return of spontaneous circulation (ROSC) accompanied by a mean
      arterial pressure at or superior to the baseline pressure and normal sinus rhythm
      for a period of 30 min. RESULTS: ROSC was achieved in only one of the control
      piglets compared with most of the treated piglets. Mortality was not
      significantly different between the three treatment groups, but was significantly
      lower in all the treatment groups compared with control. The number of ECG
      abnormalities was zero in the Intralipid only group, but 14 and 17, respectively,
      in the epinephrine and epinephrine plus lipid groups (P<0.05). CONCLUSIONS: Lipid
      emulsion with or without epinephrine, or epinephrine alone were equally effective
      in achieving a return to spontaneous circulation in this model of LAST.
      Epinephrine alone or in combination with lipid was associated with an increased
      number of ECG abnormalities compared with lipid emulsion alone.

PMID- 24091476
TI  - Radical cystectomy and orthotopic bladder substitution: surgical tricks and
      management of complications.
AB  - AIM: Bladder cancer is the second most common urological malignancy, with
      urothelial carcinoma (transitional cell carcinoma) comprising almost 90% of all
      primary bladder tumours. Over recent decades, radical cystectomy has emerged as
      the predominant treatment modality for patients with high-grade, invasive
      urothelial cancers and for those with less-invasive disease who fail treatment
      with bladder-preservation strategies. Bladder substitution following radical
      cystectomy has become increasingly common and in many centers has evolved to
      become the standard method of urinary diversion. The main goal of this paper is
      to review intraoperative considerations for patients undergoing radical
      cystectomy with a focus on issues specific to surgical tricks with neobladder
      construction and postoperative complications. METHODS: Systematic literature
      review in Pubmed and Embase including bladder cancer, urinary diversion,
      neobladder, surgical technique and complications as key words. RESULTS:
      Intraoperative techniques and modifications have made neobladder construction
      more amenable and the standard in suitable patients. Postoperative complications
      still occur in a significant number of patients but may be minimised and
      recognised early for better outcomes. CONCLUSION: Orthotopic bladder substitution
      does not compromise oncological outcome and importantly can be performed with
      relatively good results regarding functional and quality of life issues.
      Modifications to intraoperative technique can assist with neobladder construction
      to aid better outcomes. Where possible orthotopic bladder substitution should be
      the diversion of choice. Of paramount importance is the active postoperative
      management and regular long-term follow-up of patients with an orthotopic bladder
      substitution.

PMID- 24091477
TI  - Management of muscle-invasive bladder cancer.
AB  - The incidence of muscle-invasive bladder cancer (MIBC) is increasing. Many
      different and multimodal novel treatment options were brought on the way since
      the beginning of a new era in the early 1980s, when the neobladder as a common
      option for urinary diversion had been induced. In addition to open radical
      cystectomy and urinary diversion, recently, minimal invasive surgery has been
      implemented in experienced centers and led to promising results in short term
      follow-up, awaiting confirmation in larger cohorts. Pelvic lymphnode dissection
      can cure patients with low metastatic load. Expansion of pelvic lymphonodal
      dissection and its influence on survival was discussed intensively with trends to
      a moderate enlargement of the standard field. Outcome in nodal positive disease
      is remaining poor, while 90% of patients with multiple lymphnode metastases will
      suffer from systemic progress 5 years after diagnosis. In the last decade,
      treatment regimens based on neoajuvant or adjuvant chemotherapy were published
      with different results on efficiency. To decide whether to treat with surgery
      alone, or to offer perioperative systemic cytostatic therapy, is one of the
      unanswered questions. Furthermore, bladder preserving techniques are still
      optional for patients with small unifocal lesions or the medically unfit cohort.
      This review summarizes current data and aims to help guiding through several
      available recommendations on therapy and management of MIBC. 

PMID- 24091475
TI  - Small-Molecule targeting of translation initiation for cancer therapy.
AB  - Translation initiation plays a critical role in the regulation of cell growth and
      tumorigenesis. We report here that inhibiting translation initiation through
      induction of eIF2alpha phosphorylation by small-molecular-weight compounds
      restricts the availability of the eIF2.GTP.Met-tRNAi ternary complex and
      abrogates the proliferation of cancer cells in vitro and tumor growth in vivo.
      Restricting the availability of the ternary complex preferentially down-regulates
      the expression of growth-promoting proteins and up-regulates the expression of ER
      stress response genes in cancer cells as well as in tumors excised from either
      animal models of human cancer or cancer patients. These findings provide the
      first direct evidence for translational control of gene-specific expression by
      small molecules in vivo and indicate that translation initiation factors are bona
      fide targets for development of mechanism-specific anti-cancer agents. 

PMID- 24091478
TI  - Intravesical glycosaminoglycans in the management of chronic cystitis.
AB  - In this article we review the current status of evidence on the clinic
      applications of glycosaminoglycans (GAGs) in urology, with particular emphasis on
      the therapeutic use in all the chronic forms of cystitis. The so called "bladder
      layer" is mainly composed by chondroitin sulphate, dermatan sulphate and heparan
      sulphate. Demages of this mucus film seem to be involved in the pathogenesis of
      several bladder diseases. Hence, GAG replenishment therapy is widely accepted as
      a therapy for interstitial cystitis/ bladder pain syndrome (IC/BPS), recurrent
      urinary tract infections (UTIs), radiation and chemo-immunotherapy cystis and
      overactive bladder (OAB). A MEDLINE search from the first clinical application in
      1996 allowed us to find a total of 33 works regarding the use of intravesical
      GAGs. Although the evidences regarding GAG replenishment therapy are very
      encouraging in all the forms of chronic cystitis, well-powered randomized
      clinical trials are needed to better comprehend the exact role of this treatment.

PMID- 24091479
TI  - Bladder pain syndrome/interstitial cystitis: present and future treatment
      perspectives.
AB  - Bladder pain syndrome/Interstitial cystitis (BPS/IC) is a debilitating chronic
      disease of unknown etiology. Treatment is not well defined and is still under
      intense investigation. The aim of this paper was to review existing literature on
      treatment of BPS/IC and examine current evidence on present and future
      perspective. PubMed database was researched and publications in English language
      on the topic were analyzed, emphasis was given to publications that occurred on
      the last five years. Mainstays of oral therapies are still empirical due to lack
      of knowledge on etiology of this disease. The few oral drugs that showed efficacy
      in placebo controlled trials are amytriptiline, pentosan polysulfate sodium,
      hydroxyzine and cyclosporine A. As for intravesical treatments reasonable
      evidence is available only for dimethyl sulfoxide and resection of visible
      Hunner's lesions. Reconstructive surgery can also be recommended in selected
      cases. Further studies into the causes and mechanisms of the disease are
      paramount for the development of effective treatments. Foreseeable therapeutic
      objectives will comprehend oral blockade of sensory nerve receptors, immune
      system modulation, peripheral nerve fiber inactivation/desensitization, anti
      proliferative factor blockade and pain gene therapy. Identification of BPS/IC
      phenotypical subgroups should help delineate proper individualized treatment
      which will be aimed at the disease and its multiple manifestations rather than at
      focalized complaints. Present treatment of BPS/IC comprises pain control in
      conjunction with control of supposed underlying bladder disease. Based on
      identified possible therapeutic targets several treatment possibilities warrant
      further investigation. Identification of BPS/IC phenotype is a important step for
      correct management. 

PMID- 24091480
TI  - Allium stent for treatment of ureteral stenosis.
AB  - AIM: The aim of our study is to value the efficacy of self-expanding Allium
      ureteral stent in the treatment of ureteral stenosis. METHODS: From 2010 to 2013,
      we treated 12 patients, aged from 23 to 64 years. Six patients were affected by
      congenital UPJ obstruction, four patients by iatrogenic unilateral ureteral
      stenosis and two patients by bilateral ureteral stenosis. All the patients showed
      hydronephrosis before the stenotic lesion and pain. In all the patients, we use a
      30 Fr, 10 cm length self-expanding Allium ureteral stent. The medium follow-up is
      10 months after Allium stent removal. RESULTS: All the patients were immediately
      free of pain after the procedure. We didn't experience intra, peri and
      postoperative complications. In all the patients, a complete correction of the
      stenotic lesion was obtained. No recurrence of stenosis occurred during follow
      up. CONCLUSION: Self-expanding allium ureteral stent represents an effective
      treatment of ureteral stenosis in patients not suitable for surgery.

PMID- 24091481
TI  - Laparoscopic unroofing of symptomatic kidney cysts. A single center experience.
AB  - AIM: This study was aimed to evaluate success and complications of laparoscopic
      transperitoneal renal cyst unroofing and assess its long-term results at our
      center. METHODS: From October 2008 till April 2012, 23 patients (14 male and 9
      female) with a mean age of 53.6 years (range 32-70), underwent transperitoneal
      laparoscopic renal cyst unroofing at our center. None of the patients, had
      history of ipsilateral kidney surgery. Complication and outcomes were evaluated.
      Symptom resolving and disappearance of the cyst or decreasing its size to less
      than 1/3 of its primary size in radiographies was considered as success. RESULTS:
      Unroofing was achieved in 100% of patients. Mean operative time was 36.6 minutes
      (range 25 to 60) and mean hospital stay was 3 days (range 2 to 8). No open
      conversions were necessary during procedure but one patient underwent open
      exploration hours after laparoscopy because of need to complete hemostasis.
      Symptomatic and radiologic success was achieved in 91.3% of patients, with a mean
      follow-up of 15 months (range 3 to 24). One patient developed a recurrence. One
      ureter stricture revealed in follow up period which needed open uretero
      ureterostomy. No visceral complication occurred. CONCLUSION: Laparoscopic
      transperitoneal ureterolithotomy is an effective treatment option for skilled
      surgeons but care must be taken because complications may occur.

PMID- 24091482
TI  - Daily step count is associated with plasma C-reactive protein and IL-6 in a US
      cohort with COPD.
AB  - BACKGROUND: Physical activity is an important clinical marker of disease status
      in COPD. COPD is also characterized by low-grade systemic inflammation. However,
      the relationship between physical activity and systemic inflammation in COPD is
      unclear. METHODS: We monitored daily step count, a directly measured physical
      activity, using the StepWatch Activity Monitor, an ankle-worn accelerometer, in
      171 people with stable COPD. Exercise capacity was assessed with the 6-min walk
      test (6MWT). We measured plasma C-reactive protein (CRP) and IL-6 levels. Linear
      regression models examined the cross-sectional associations of daily step count
      and 6MWT distance with CRP and IL-6 levels. RESULTS: Subjects had a mean age 72+/
      8 years and mean FEV1 1.5+/-0.57 L (54+/-20% predicted). Median daily step count
      was 5,203 (interquartile range [IQR], 3,627-7,024], CRP level was 2.4 mg/L (IQR,
      1.2-5.0), and IL-6 level was 2.9 pg/mL (IQR, 2.0-5.1). Each 1,000-step increase
      in daily step count was associated with a 0.94 mg/L and 0.96 pg/mL decrease in
      CRP (P=.020) and IL-6 (P=.044) levels, respectively, adjusting for age, FEV1 %
      predicted, pack-years smoked, cardiac disease, current statin use, history of
      acute exacerbations, and season. There was a significant linear trend of
      increasing daily step count by quartiles and decreasing CRP (P=.0007) and IL-6
      (P=.023) levels. Higher 6MWT distance was also significantly associated with
      lower CRP and IL-6 values. CONCLUSION: People with COPD who walked the most had
      the lowest plasma CRP and IL-6 levels. These results provide the conceptual basis
      to study whether an intervention to promote walking will reduce systemic
      inflammation in people with COPD.

PMID- 24091483
TI  - Multiple pharmacy use and types of pharmacies used to obtain prescriptions.
AB  - OBJECTIVES: To evaluate trends and patterns in the prevalence of multiple
      pharmacy use (MPU) and to describe the number and types of pharmacies used by
      multiple pharmacy users from 2003 to 2009. DESIGN: Retrospective, cross
      sectional, descriptive study. SETTING: United States from 2003 to 2009.
      PARTICIPANTS: 89,941 responses to the Medical Expenditure Panel Survey over 7
      years. INTERVENTION: Analysis of respondent pharmacy use behaviors. MAIN OUTCOME
      MEASURES: Annual use of more than one pharmacy and number and types of pharmacies
      used. RESULTS: MPU among patients using medications increased significantly
      during the study period (from 36.4% [95% CI 35.2-37.6] in 2003 to 43.2% [41.9
      44.4] in 2009)-a relative increase of 18.7% ( P = 0.01). Multiple pharmacy users
      used between 2 and 17 different pharmacies per year to obtain prescription
      medications. Although approximately 70% of multiple pharmacy users used only two
      pharmacies, the proportion using three or more pharmacies increased from 24.1%
      (22.5-25.7) in 2003 to 29.1% (27.4-30.8) in 2009. Mail service pharmacy use had
      the largest relative increase among multiple pharmacy users during the study
      period (27.2%), and MPU was nearly twice as high (75%) among mail service users
      compared with non-mail service users. CONCLUSION: MPU is common on a national
      level and has increased greatly in recent years. Patient use of pharmacies that
      have the potential to share medication information electronically is low among
      multiple pharmacy users, suggesting increased workload for pharmacists and
      potential medication safety concerns. This has important implications for
      pharmacists, as it potentially impedes their ability to maintain accurate
      medication profiles for patients.

PMID- 24091484
TI  - Endometrial polyps detected at ultrasound and rate of malignancy.
AB  - PURPOSE: The vast majority of the evidence on the prevalence of malignancy in
      endometrial polyps was obtained irrespectively of the time of diagnosis, i.e.
      including both women who were diagnosed at pre-surgical ultrasound and those who
      were diagnosed at the time of hysteroscopy. We hypothesize that this may
      represent an inaccuracy of potential clinical relevance since physicians have to
      take decisions regarding the need of surgery at the time of ultrasound diagnosis.
      MATERIALS AND METHODS: Medical records of 2,245 patients who underwent
      hysteroscopy during a 4-year period were reviewed. Inclusion criterion was a pre
      operative diagnosis of endometrial polyps. RESULTS: 1,284 women (57 % of the
      cohort) were selected, of whom 36 were diagnosed with malignancies (2.8 %, 95 %
      CI 2.0-3.8). This prevalence markedly differ in pre- and post-menopause, being
      higher in the latter group (OR = 9.0, 95 % CI 2.6-30.3, p < 0.001). Six out of
      803 resulted positive in the pre-menopausal group (0.7 %, 95 % CI 0.3-1.5)
      compared to 30 out of 481 in the post-menopausal group (6.2 %, 95 % CI 4.3-8.6).
      In the pre-menopausal group, a younger age resulted protective. The risk of
      malignancy in women younger than 50 years was 0.3 % (95 % CI 0.04-0.9). In the
      post-menopausal group, abnormal uterine bleeding (AUB) was associated with a
      diagnosis of malignancy (OR = 4.0, 95 % CI 1.9-8.5). The prevalence of malignancy
      in symptomatic and asymptomatic post-menopausal women was 11.8 % (95 % CI 7.6
      17.1) and 3.0 % (95 % CI 1.4-5.3), respectively. CONCLUSIONS: The prevalence of
      malignancy among endometrial polyps detected at ultrasound is low and in line
      with the evidence obtained for a diagnosis made at the time of surgery. Some
      simple anamnestic information such as menopausal status, age and AUB helps
      identify women at higher risk and should be used in the decision-making process
      guiding the choice of surgery.

PMID- 24091485
TI  - The relationship between maternal serum prenatal screening combined with
      epidemiological study and early onset preeclampsia.
AB  - OBJECTIVE: To explore the major risk factors and early prediction methods in the
      pathogenesis of early onset preeclampsia through combining prenatal screening
      markers and epidemiological characteristics. METHODS: Prenatal screening was
      performed in second trimester using enzyme-linked immunosorbent assay in 1,011
      gravidas and epidemiological correlation factors were got by telephone with
      prospective cohort study. Predictive model of early onset preeclampsia was
      established and evaluated by single and multiple factor logistic analysis in 30
      cases of preeclampsia and 867 cases of normal gravidas. RESULTS: As compared with
      the control group, the maternal serum level of human chorionic gonadotropin (hCG)
      in second trimester of patients with early onset preeclampsia elevated
      significantly (P < 0.001). Pregestational BMI >= 24 kg/m(2) (OR = 3.649, 95 % CI
      1.600-8.321, P = 0.002), history of hypertension, diabetes and nephritis (OR =
      55.724, 95 % CI 8.223-377.614, P < 0.001), family history of hypertension (OR =
      6.777, 95 % CI 2.917-15.742, P < 0.001), and risk coefficient for trisomy 21 (OR
      = 3.688, 95 % CI 1.013-13.429, P = 0.048) were major risk factors of early onset
      preeclampsia. The sensitivity and specificity of predictive model were 70.0 and
      75.1 %, when cutoff point was 0.249. The diagnostic accuracy of the logistic
      model was better than hCG. CONCLUSIONS: In order to early prevent the onset and
      development of EOPE, it is necessary to strengthen pregestational and prenatal
      care for women in these aspects including pregestational BMI >= 24 kg/m(2),
      history of hypertension, diabetes, nephritis, family history of hypertension, and
      high risk for trisomy 21 syndrom.

PMID- 24091487
TI  - Appearance distress and dysfunction in the elderly: international contrasts
      across Italy and the UK using DAS59.
AB  - BACKGROUND: As the global population grows, the percentage of those over 60 will
      escalate disproportionately. Their needs will become an ever more dominant
      feature of public policy and healthcare provision. Older adults' appearance is
      often removed from cultural ideals and stereotypes of beauty, often seen as
      synonymous with "youth." This has seen older adults' concerns about appearance
      and body image somewhat sidelined in practice and in research. This study
      investigates the extent to which self-consciousness of appearance is associated
      with distress and dysfunction in those over 60 years old. Furthermore, we
      contrast the extent of this phenomenon in two European nations, UK and Italy, and
      consider the direct impact and interaction of cultural context and participant
      gender. METHOD: To make an objective measurement of distress and dysfunction, we
      translated a widely used psychometric measure, the Derriford Appearance Scale 59
      following an established and reliable translation protocol. Data were collected
      from community samples. RESULTS: The Italian translation was sound, with
      acceptability in the Italian-speaking sample and acceptable internal consistency
      scores for full-scale and subscales. ANOVA analysis demonstrated that for overall
      adjustment, and all subscale scores, the Italians were more distressed about
      their appearance than UK comparators. Moreover, there were significant
      differences between Italian women and men, with Italian women more distressed
      than Italian men overall, and also general self-consciousness, sexual self
      consciousness, and social self-consciousness subscales. CONCLUSION: These results
      are considered in the context of aging and cultural and gender issues in
      appearance, including the Italian concept of bella figura. LEVEL OF EVIDENCE IV:
      This journal requires that authors assign a level of evidence to each article.
      For a full description of these Evidence-Based Medicine ratings, please refer to
      the Table of Contents or the online Instructions to Authors
      www.springer.com/00266 .

PMID- 24091488
TI  - Improved scar appearance with combined use of silicone gel and vitamin C for
      Asian patients: a comparative case series.
AB  - BACKGROUND: In Asians, facial scars, even fine surgical scars, often can be
      conspicuous and uncomfortable. The authors used a topical silicone gel containing
      vitamin C on facial scars for the purpose of making the scar less distinct.
      METHODS: The study enrolled 80 patients. For the experimental group, the topical
      silicone gel mixture containing vitamin C was applied from the time of stitch
      removal to 6 months after the operation. The control group did not undergo any
      adjunctive treatment. Each participant was evaluated using the modified Vancouver
      Scar Scale (VSS) as well as erythema and melanin indices by spectrophotometer.
      RESULTS: With the modified VSS, the experimental group showed a significant
      decrease in scar elevation (p = 0.026) and erythema (p = 0.025). The hypo- or
      hyperpigmentation of the scars was more normalized in the experimental group. In
      the measured results via spectrophotometer, the experimental group showed a
      significant decrease in the melanin index (p = 0.045). The erythema index showed
      a statistically significant difference between the time of stitch removal and 6
      months after the operation in the experiment group only. CONCLUSIONS: Topical use
      of silicone gel containing vitamin C has the effect of improving the appearance
      of fine surgical scars in Asian facial skin. LEVEL OF EVIDENCE IV: This journal
      requires that authors assign a level of evidence to each article. For a full
      description of these Evidence-Based Medicine ratings, please refer to the Table
      of Contents or the online Instructions to Authors www.springer.com/00266 .

PMID- 24091489
TI  - Economic analysis and review of the literature on implant-based breast
      reconstruction with and without the use of the acellular dermal matrix.
AB  - BACKGROUND: Use of the acellular dermal matrix (ADM) in two-stage implant-based
      breast reconstruction has been widely adopted. Despite an increasing focus on
      health care costs, few reports have addressed the financial implications of ADM
      use. This study sought to examine the costs of the two-stage technique with and
      without ADM, concentrating on the direct variable costs of patient care during
      the expansion process. METHODS: A retrospective review of a prospectively
      maintained database was conducted. Data were collected on 132 cases resulting in
      a second-stage exchange for a permanent implant. The findings showed that
      AlloDerm was used in 61 reconstructions and Strattice in 23 reconstructions. The
      primary outcome was the number of fills required to achieve the final expander
      fill volume. The cost of subsequent patient encounters for expansion was
      estimated using institutional cost data. RESULTS: The number of fills required to
      achieve the final volume was higher in the non-ADM group (6.5 +/- 1.7) than in
      the ADM group (3.6 +/- 1.4) (p < 0.0001). No significant difference was found in
      the small fill volumes (<350 ml; 5.3 vs. 3.7; p > 0.05). The difference was
      significant in the larger fill volumes (>500 ml; 8.3 vs. 3.7; p < 0.05). Relative
      to non-ADM reconstruction, with AlloDerm at current prices, the cost increase
      ranged from $2,727.75 for large reconstructions to $3,290.25 for small
      reconstructions ($2,167.75-$2,739.25 with Strattice). CONCLUSION: The use of ADM
      in two-stage reconstruction reduces the number of visits required for
      reconstructions with 350 ml or more. However, at current pricings, the direct
      cost of ADM use does not offset the cost savings from the reduced number of
      visits. LEVEL OF EVIDENCE IV: This journal requires that authors assign a level
      of evidence to each article. For a full description of these Evidence-Based
      Medicine ratings, please refer to the Table of Contents or the online
      Instructions to Authors www.springer.com/00266 .

PMID- 24091490
TI  - Editor's invited commentary: Does reduction mammaplasty revert skeletal
      disturbances in the vertebral column of patients with macromastia? A preliminary
      study.

PMID- 24091491
TI  - Use of a sternocleidomastoid myocutaneous flap based on the sternocleidomastoid
      branch of the superior thyroid artery to reconstruct extensive cheek defects.
AB  - INTRODUCTION: Reconstruction of head and neck defects has always been challenging
      due to functional and cosmetic concerns. Although sternocleidomastoid (SCM) flaps
      have been used for many head and neck defects, use of an SCM flap to reconstruct
      a cheek defect based only on the superior thyroid artery has not been reported
      previously. CASE REPORT: The case of a 40-year-old farmer with a large full
      thickness cheek squamous cell carcinoma is reported. An SCM myocutaneous flap
      based on the SCM branch of the superior thyroid artery was used. CONCLUSION: An
      SCM myocutaneous flap is a valuable option for head and neck reconstructions with
      reasonable aesthetic results. For properly selected cases, this flap obviates the
      need to use the pectoralis major or other more distant flaps. LEVEL OF EVIDENCE
      V: This journal requires that authors assign a level of evidence to each article.
      For a full description of these Evidence-Based Medicine ratings, please refer to
      the Table of Contents or the online Instructions to Authors
      www.springer.com/00266 .

PMID- 24091486
TI  - Postmortem brain: an underutilized substrate for studying severe mental illness.
AB  - We propose that postmortem tissue is an underutilized substrate that may be used
      to translate genetic and/or preclinical studies, particularly for
      neuropsychiatric illnesses with complex etiologies. Postmortem brain tissues from
      subjects with schizophrenia have been extensively studied, and thus serve as a
      useful vehicle for illustrating the challenges associated with this biological
      substrate. Schizophrenia is likely caused by a combination of genetic risk and
      environmental factors that combine to create a disease phenotype that is
      typically not apparent until late adolescence. The complexity of this illness
      creates challenges for hypothesis testing aimed at understanding the
      pathophysiology of the illness, as postmortem brain tissues collected from
      individuals with schizophrenia reflect neuroplastic changes from a lifetime of
      severe mental illness, as well as treatment with antipsychotic medications. While
      there are significant challenges with studying postmortem brain, such as the
      postmortem interval, it confers a translational element that is difficult to
      recapitulate in animal models. On the other hand, data derived from animal models
      typically provide specific mechanistic and behavioral measures that cannot be
      generated using human subjects. Convergence of these two approaches has led to
      important insights for understanding molecular deficits and their causes in this
      illness. In this review, we discuss the problem of schizophrenia, review the
      common challenges related to postmortem studies, discuss the application of
      biochemical approaches to this substrate, and present examples of postmortem
      schizophrenia studies that illustrate the role of the postmortem approach for
      generating important new leads for understanding the pathophysiology of severe
      mental illness. 

PMID- 24091492
TI  - Evaluation of pedicled omental flap delivered through a minilaparotomy for
      immediate breast reconstruction in obese patients.
AB  - BACKGROUND: Studies have shown the laparoscopically harvested omental flap to be
      a successful method for immediate breast reconstruction. However, data about its
      usefulness and safety in obese women are limited. This study examined the
      effectiveness and safety of a pedicled omental flap delivered via a
      minilaparotomy in women with a body mass index (BMI) higher than 30 kg/m(2).
      METHODS: Women candidates for skin-sparing mastectomy underwent reconstruction
      with delivery of a pedicled omental flap via a minilaparotomy. RESULTS: Surgery
      was performed for 24 women with a mean age of 57.54 years and a mean BMI of 32.54
      kg/m(2). The operative time was prolonged by about 1 h without excess blood loss
      or prolongation of their hospital stay. Except for a single case of partial flap
      necrosis, no single total flap loss was recorded. In three patients (12.5 %), the
      flap volume was inadequate, and silicone implant was used as an adjunct. Only one
      patient (4 %) experienced a small incisional hernia. The majority of the patients
      (67 %) described their cosmetic outcome as excellent. CONCLUSION: Delivery of a
      pedicled omental flap via a minilaparotomy is a safe and reliable method for
      immediate breast reconstruction after skin-sparing mastectomy in women with a BMI
      higher than 30 kg/m(2). LEVEL OF EVIDENCE V: This journal requires that authors
      assign a level of evidence to each article. For a full description of these
      Evidence-Based Medicine ratings, please refer to the Table of Contents or the
      online Instructions to Authors www.springer.com/00266 .

PMID- 24091494
TI  - The right way to self-fuse bi- and terpyrenyls to afford graphenic cutouts.
AB  - In this work, we subject bi- and terpyrenyls to selective fusion for formation of
      extended polycyclic aromatic hydrocarbons (PAHs). Connecting the pyrene units at
      4-4'- or 1-4'-positions led to smooth formation of extended PAHs, achieved via
      cyclodehydrogenation. This is far more difficult if pyrene is coupled in the 1,1'
      position. 

PMID- 24091495
TI  - Ferromagnetic 1D oxide nanostructures grown from chemical solutions in confined
      geometries.
AB  - This review summarizes the capabilities and recent developments of nanoporous
      polymeric template systems directly supported on different substrates for the
      confined growth of epitaxial ferromagnetic complex oxide 1D nanostructures. In
      particular, we describe the versatility and potentiality of chemical solutions
      combined with track-etched polymers to synthesize (i) vertical polycrystalline
      La0.7Sr0.3MnO3 nanorods on top of single crystal perovskites, (ii) single
      crystalline manganese based octahedral molecular sieve (OMS) nanowires on silicon
      substrates, and (iii) the epitaxial directional single crystal OMS nanowires on
      top of fluorite-type substrates. The influence of the distinct growth parameters
      on the nanostructural evolution of the resulting nanostructures and their
      magnetic properties is further discussed in detail. 

PMID- 24091496
TI  - Regulation of angiogenesis, mural cell recruitment and adventitial macrophage
      behavior by Toll-like receptors.
AB  - The angiogenic response to injury can be studied by culturing rat or mouse aortic
      explants in collagen gels. Gene expression studies show that aortic angiogenesis
      is preceded by an immune reaction with overexpression of Toll-like receptors
      (TLRs) and TLR-inducible genes. TLR1, 3, and 6 are transiently upregulated at 24
      h whereas TLR2, 4, and 8 expression peaks at 24 h but remains elevated during
      angiogenesis and vascular regression. Expression of TLR5, 7 and 9 steadily
      increases over time and is highest during vascular regression. Studies with
      isolated cells show that TLRs are expressed at higher levels in aortic
      macrophages compared to endothelial or mural cells with the exception of TLR2 and
      TLR9 which are more abundant in the aortic endothelium. LPS and other TLR ligands
      dose dependently stimulate angiogenesis and vascular endothelial growth factor
      production. TLR9 ligands also influence the behavior of nonendothelial cell types
      by blocking mural cell recruitment and inducing formation of multinucleated giant
      cells by macrophages. TLR9-induced mural cell depletion is associated with
      reduced expression of the mural cell recruiting factor PDGFB. The spontaneous
      angiogenic response of the aortic rings to injury is reduced in cultures from
      mice deficient in myeloid differentiation primary response 88 (MyD88), a key
      adapter molecule of TLRs, and following treatment with an inhibitor of the
      NFkappaB pathway. These results suggest that the TLR system participates in the
      angiogenic response of the vessel wall to injury and may play an important role
      in the regulation of inflammatory angiogenesis in reactive and pathologic
      processes. 

PMID- 24091497
TI  - Distinct roles of DKK1 and DKK2 in tumor angiogenesis.
AB  - Tumor angiogenesis is essential for tumor invasive growth and metastasis, and
      generates abnormal vascular structures unlike developmental neovessel formation.
      To reduce tumor vascular abnormalities such as leakage and perivascular cell
      coverage deficiency that limit cancer therapy effectiveness, novel therapeutic
      approaches focus on vessel normalization. We have previously shown that Dickkopf
      1 (DKK1), a Wnt antagonist, inhibits and its homolog DKK2 enhances, angiogenesis
      in normal tissues. In the present study, we investigated the effects of DKK1 and
      DKK2 on tumor growth and angiogenesis. Treatment of B16F10 melanoma-bearing mice
      with adenovirus expressing DKK1 significantly reduced tumor growth but DKK2
      increased growth compared with controls. Similar pattern of tumor growth was
      observed in endothelial-specific DKK1 and DKK2 transgenic mice. Interestingly,
      tumor vascular density and perfusion were significantly decreased by DKK1 but
      increased by DKK2. Moreover, coverage of blood vessels by pericytes was reduced
      by DKK1, while DKK2 increased it. We further observed that DKK1 diminished
      retinal vessel density and increased avascular area in an in vivo murine model of
      oxygen-induced retinopathy, whereas DKK2 showed opposite results. These findings
      demonstrate that DKK1 and DKK2 have differential roles in normalization and
      functionality of tumor blood vessels, in addition to angiogenesis. 

PMID- 24091500
TI  - A low-residue breakfast improves patient tolerance without impacting quality of
      low-volume colon cleansing prior to colonoscopy: a randomized trial.
AB  - OBJECTIVES: We compared the efficacy and patient tolerance of two dietary
      regimens used as an adjunct to standard bowel cleansing in preparation for
      elective colonoscopy. METHODS: Our prospective, randomized, single-blind,
      controlled, noninferiority trial compared two dietary regimens administered the
      day before colonoscopy. Subjects received low-volume bowel preparation. The
      primary outcome was efficacy of colon cleansing, rated by the Ottawa bowel
      preparation scale (OBPS). Patient acceptance of the assigned dietary regimen was
      assessed as a secondary outcome. RESULTS: The mean OBPS score for the standard
      clear-fluid diet group was 4.47, compared with 4.62 for the low-residue breakfast
      group, meeting criteria for noninferiority. The groups reported similar mean
      intensity of hunger on a visual analog hunger scale. However, overall
      satisfaction was higher with the low-residue diet than with the clear-fluid diet.
      CONCLUSIONS: A low-residue breakfast on the day before elective colonoscopy does
      not compromise the overall quality of bowel preparation as compared with a
      standard clear-fluid diet and is likely to be preferred by patients.

PMID- 24091499
TI  - Pancreatic cyst prevalence and the risk of mucin-producing adenocarcinoma in US
      adults.
AB  - OBJECTIVES: The presence of a pancreatic cyst often prompts concern, although the
      rate of malignant transformation to mucin-producing adenocarcinoma is not known.
      We aimed to determine the prevalence rate of mucin-producing adenocarcinoma in US
      adults with pancreatic cysts. METHODS: This retrospective, population-based cross
      sectional study calculated the annual number of mucin-producing adenocarcinomas
      using the Surveillance Epidemiology and End Results (SEER 18) database and the
      2010 US census. The overall prevalence rate of cysts in the population was found
      using data from large cross-sectional imaging studies of incidental cyst
      prevalence. Prevalence rates were then calculated by dividing the annual number
      of mucin-producing adenocarcinomas by the cyst prevalence rate. RESULTS: Between
      2005 and 2009, 1,137 mucin-producing adenocarcinomas were estimated to be found
      annually in a US adult population of 137,154,960. The total number of pancreas
      cysts, given a cyst prevalence rate of 2.5%, was 3,428,874. Therefore, the
      prevalence rate of mucin-producing adenocarcinoma arising in patients with
      pancreatic cysts was 33.2 per 100,000 (95% confidence interval (CI): 21.9-44.5).
      The prevalence rate was 32.8 per 100,000 (95% CI: 21.6-44.0) in women and 33.5
      per 100,000 (95% CI: 22.2-44.8) in men. As expected, the rate of malignant
      transformation increased linearly with advancing age (highest 38.6 per 100,000 in
      80- to 84-year-old men). CONCLUSIONS: Malignant transformation of pancreatic
      cysts into mucin-producing adenocarcinoma in US adults is a very rare event.
      Current clinical guidelines and resource allocation for pancreatic cyst disease
      should be reconsidered given these findings.

PMID- 24091501
TI  - Image of the month: "butterfly" effect, or mirror image, caused by a coiled
      esophageal manometry catheter.

PMID- 24091506
TI  - Curbing our enthusiasm for fecal transplantation in ulcerative colitis.
AB  - Given the known dysbiosis of gut microflora in inflammatory bowel disease, there
      has been great enthusiasm about the potential for fecal microbiota
      transplantation (FMT) as a treatment. This editorial accompanies a prospective
      series of five patients with ulcerative colitis who underwent FMT, but did not
      achieve remission. I discuss the important observations from this study and point
      out that the lack of clinical efficacy and observed side effects warrant caution
      in the ongoing pursuit of this treatment option. 

PMID- 24091507
TI  - PARs for the course: roles of proteases and PAR receptors in subtly inflamed
      irritable bowel syndrome.
AB  - Although the etiology of irritable bowel syndrome (IBS) remains unknown, clinical
      and laboratory observations suggest that within the broad and varying phenotype,
      that is, IBS, there may exist subgroups, which can be defined on the basis of a
      distinctive pathophysiological basis. Of these, postinfectious IBS is the best
      characterized; in IBS, in general, studies of inflammatory mediators and
      substances elaborated by cells involved in the intestinal immune response, such
      as proteases, suggest that some IBS sufferers can be differentiated on the basis
      of an aberrant immune response. Valdez-Morales and colleagues extend this concept
      by demonstrating the ability of supernatants of biopsy cultures from individuals
      with diarrhea-predominant IBS to enhance neuronal excitability-an effect that
      could well contribute to a clinical hallmark of IBS, namely, visceral
      hypersensitivity. 

PMID- 24091508
TI  - Stretta radiofrequency treatment for GERD: a safe and effective modality.

PMID- 24091509
TI  - Stretta for refractory GERD: now more than ever.

PMID- 24091510
TI  - Response to Franciosa et al. and Triadafilopoulos.

PMID- 24091511
TI  - Non-erosive reflux disease is more complex than negative endoscopy only.

PMID- 24091512
TI  - Response to Savarino et al.

PMID- 24091513
TI  - Split donation fecal microbiota transplantation.

PMID- 24091514
TI  - Response to Gutman and Kurchin: we are not cisterns made for hoarding.

PMID- 24091515
TI  - Is there any place for spleen stiffness measurement in portal hypertension?

PMID- 24091516
TI  - Response to Stefanescu et al.

PMID- 24091517
TI  - Physician outlook toward fecal microbiota transplantation in the treatment of
      Clostridium difficile infection.

PMID- 24091518
TI  - Massive gastrointestinal bleeding secondary to superior mesenteric arteriovenous
      fistula.

PMID- 24091519
TI  - Mega-cecum: a novel clinical entity which explains overlapping gastrointestinal
      and urogynecologic symptoms in women with chronic constipation.

PMID- 24091520
TI  - Case series: does a combination of anti-tnf antibodies and transient ileal fecal
      stream diversion in severe Crohn's colitis with perianal fistula prevent
      definitive stoma?

PMID- 24091525
TI  - Bioremediation assessment of diesel-biodiesel-contaminated soil using an
      alternative bioaugmentation strategy.
AB  - This study investigated the effectiveness of successive bioaugmentation,
      conventional bioaugmentation, and biostimulation of biodegradation of B10 in
      soil. In addition, the structure of the soil microbial community was assessed by
      polymerase chain reaction-denaturing gradient gel electrophoresis. The consortium
      was inoculated on the initial and the 11th day of incubation for successive
      bioaugmentation and only on the initial day for bioaugmentation and conventional
      bioaugmentation. The experiment was conducted for 32 days. The microbial
      consortium was identified based on sequencing of 16S rRNA gene and consisted as
      Pseudomonas aeruginosa, Achromobacter xylosoxidans, and Ochrobactrum intermedium.
      Nutrient introduction (biostimulation) promoted a positive effect on microbial
      populations. The results indicate that the edaphic community structure and
      dynamics were different according to the treatments employed. CO2 evolution
      demonstrated no significant difference in soil microbial activity between
      biostimulation and bioaugmentation treatments. The total petroleum hydrocarbon
      (TPH) analysis indicated a biodegradation level of 35.7 and 32.2 % for the
      biostimulation and successive bioaugmentation treatments, respectively.
      Successive bioaugmentation displayed positive effects on biodegradation, with a
      substantial reduction in TPH levels.

PMID- 24091526
TI  - Integration of geophysical, geochemical and microbiological data for a
      comprehensive small-scale characterization of an aged LNAPL-contaminated site.
AB  - Characterization of aged hydrocarbon-contaminated sites is often a challenge due
      to the heterogeneity of subsurface conditions. Geoelectrical methods can aid in
      the characterization of such sites due to their non-invasive nature, but need to
      be supported by geochemical and microbiological data. In this study, a
      combination of respective methods was used to characterize an aged light non
      aqueous phase liquid-contaminated site, which was the scene of a crude oil blow
      out in 1994. As a consequence, a significant amount of crude oil was released
      into the subsurface. Complex resistivity has been acquired, both along single
      boreholes and in cross-hole configuration, in a two-borehole test site addressed
      with electrodes, to observe the electrical behaviour at the site over a two-year
      period (2010-2011). Geoelectrical response has been compared to results of the
      analysis of hydrocarbon contamination in soil and groundwater samples.
      Geochemical parameters of groundwater have been observed by collecting samples in
      a continuous multi-channel tubing (CMT) piezometer system. We have also performed
      a biological characterization on soil samples by drilling new boreholes close to
      the monitoring wells. Particular attention has been given to the characterization
      of the smear zone that is the sub-soil zone affected by the seasonal groundwater
      fluctuations. In the smear zone, trapped hydrocarbons were present, serving as
      organic substrate for chemical and biological degradation, as was indicated by an
      increase of microbial biomass and activity as well as ferrogenic-sulfidogenic
      conditions in the smear zone. The results show a good agreement between the
      intense electrical anomaly and the peaks of total organic matter and degradation
      by-products, particularly enhanced in the smear zone. 

PMID- 24091527
TI  - Factors affecting xylene-contaminated air removal by the ornamental plant
      Zamioculcas zamiifolia.
AB  - Fifteen plant species-Alternanthera bettzickiana, Drimiopsis botryoides, Aloe
      vera, Chlorophytum comosum, Aglaonema commutatum, Cordyline fruticosa,
      Philodendron martianum, Sansevieria hyacinthoides, Aglaonema rotundum, Fittonia
      albivenis, Muehlenbeckia platyclada, Tradescantia spathacea, Guzmania lingulata,
      Zamioculcas zamiifolia, and Cyperus alternifolius-were evaluated for the removal
      efficiency of xylene from contaminated air. Among the test plants, Z. zamiifolia
      showed the highest xylene removal efficiency. Xylene was toxic to Z. zamiifolia
      with an LC50 of 3,464 ppm. Higher concentrations of xylene exhibited damage
      symptoms, including leaf tips turning yellow, holonecrosis, and hydrosis. TEM
      images showed that a low concentration of xylene vapors caused minor changes in
      the chloroplast, while a high concentration caused swollen chloroplasts and
      damage. The effect of photosynthetic types on xylene removal efficiency suggests
      that a mixture of Z. zamiifolia, S. hyacinthoides, and A. commutatum which
      represent facultative CAM, CAM, and C3 plants, is the most suitable system for
      xylene removal. Therefore, for maximum improvement in removing xylene volatile
      compounds under various conditions, multiple species are needed. The effect of a
      plant's total leaf area on xylene removal indicates that at lower concentrations
      of xylene, a small leaf area might be as efficient as a large leaf area. 

PMID- 24091528
TI  - The potential of the flora from different regions of Pakistan in
      phytoremediation: a review.
AB  - Soil and water quality is greatly affected by environmental pollution due to the
      increasing trend of urbanization and industrialization. In many developing
      countries, including Pakistan, the situation is more alarming as no preventive
      measures are still taken to tackle the problem. Although in developed countries,
      many techniques are used to remediate the environment including phytoremediation.
      It is the most eco-friendly technique in which plants are used to remove
      pollutants from the environment. Pakistan has also a great diversity of plants
      which could be used for the remediation of environmental pollutants. To our
      knowledge, few studies from Pakistan were reported about the use of flora for
      phytoremediation. According to recent literature, 50 plant species from Pakistan
      are studied for remediation purposes. In this review, the potential of different
      plant species for phytoremediation from Pakistan has been discussed along with
      their comparison to other countries to relate future perspectives. 

PMID- 24091530
TI  - TRPC1: getting physical in space.

PMID- 24091529
TI  - Molecular imaging of drug transit through the blood-brain barrier with MALDI mass
      spectrometry imaging.
AB  - Drug transit through the blood-brain barrier (BBB) is essential for therapeutic
      responses in malignant glioma. Conventional methods for assessment of BBB
      penetrance require synthesis of isotopically labeled drug derivatives. Here, we
      report a new methodology using matrix assisted laser desorption ionization mass
      spectrometry imaging (MALDI MSI) to visualize drug penetration in brain tissue
      without molecular labeling. In studies summarized here, we first validate heme as
      a simple and robust MALDI MSI marker for the lumen of blood vessels in the brain.
      We go on to provide three examples of how MALDI MSI can provide chemical and
      biological insights into BBB penetrance and metabolism of small molecule signal
      transduction inhibitors in the brain - insights that would be difficult or
      impossible to extract by use of radiolabeled compounds. 

PMID- 24091532
TI  - Rapamycin prolongs female reproductive lifespan.

PMID- 24091531
TI  - Mouse oocyte, a paradigm of cancer cell.

PMID- 24091533
TI  - Genome organization by Klf4 regulates transcription in pluripotent stem cells.

PMID- 24091534
TI  - To target or not to target the enemy within localized prostate cancer.

PMID- 24091535
TI  - PI3K/AKT addiction in subsets of diffuse large B-cell lymphoma.

PMID- 24091537
TI  - Herniation of transverse colon into mediastinum after pedicled omental grafting
      for mediastinitis: report of a case.
AB  - We describe a rare complication and the treating experience of it after pedicled
      omental grafting for mediastinitis. The patient was diagnosed as an acute
      mediastinitis soon after the total arch replacement was performed. A two-staged
      strategy to treat postoperative mediastinitis was scheduled, i.e., the setting up
      of a vacuum-assisted closure system until the improvement of inflammation
      followed by wound closure with pedicled omental grafting. The treatment for acute
      mediastinitis was successful and the patient followed a favorable postoperative
      course. During the follow-up, chest X-ray film suggested the gradual enlargement
      of mediastinum and CT showed the herniation of transverse colon into mediastinum.
      Surgical correction for the hernia was scheduled and performed successfully by
      the laparoscopic procedure to prevent a possible cardiac and pulmonary
      dysfunction.

PMID- 24091536
TI  - The mysterious presence of a 5-methylcytosine oxidase in the Drosophila genome:
      possible explanations.

PMID- 24091538
TI  - Enhancing optical absorption of metal-organic frameworks for improved visible
      light photocatalysis.
AB  - NH2-MIL-125(Ti) has been post-synthetically functionalized with dye-like
      molecular fragments. The new material (methyl red-MIL-125(Ti)) exhibits improved
      light absorption over a wide range of the visible spectrum, and shows enhanced
      photocatalytic oxidation activity under visible light illumination. The
      consequences of functionalization and the bottlenecks in MOF photochemistry are
      studied in detail. 

PMID- 24091539
TI  - Subscapularis partial tear nodule causing shoulder rotational triggering.
AB  - Subscapularis nodules are rare causes of shoulder pain. There have been no
      reports of nodular swellings arising from the articular surface of the
      subscapularis tendon. We report two original cases of intra-articular subscapular
      nodules with reciprocal middle glenohumeral ligament thickening. In both cases,
      the patients had long standing deep-seated anterior shoulder pain with failed
      conservative treatments. Arthroscopy, magnetic resonance imaging and histology
      reports revealed nodules with underlying partial subscapularis tears. Arthroscopy
      may be needed to identify and successfully treat rare symptomatic nodules as
      causes of pain and clicking in the shoulder joint. LEVEL OF EVIDENCE: V.

PMID- 24091541
TI  - Formation of MS-Ag and MS (M = Pb, Cd, Zn) nanotubes via microwave-assisted
      cation exchange and their enhanced photocatalytic activities.
AB  - A facile microwave-assisted cation-exchange reaction route has been developed to
      synthesize a series of MS-Ag (M = Pb, Cd, Zn) heterostructure nanotubes (HSNTs)
      and MS nanotubes. As a demonstration, the as-prepared PbS-Ag HSNTs exhibit
      significantly enhanced photocatalytic activity for degradation of Congo red and
      reduction of Cr(VI). 

PMID- 24091540
TI  - Diagnostic utility of whole exome sequencing in patients showing cerebellar
      and/or vermis atrophy in childhood.
AB  - Cerebellar and/or vermis atrophy is recognized in various types of childhood
      disorders with clinical and genetic heterogeneity. Although careful evaluation of
      clinical features and neuroimaging can lead to correct diagnosis of disorders,
      their diagnosis is sometimes difficult because clinical features can overlap with
      each other. In this study, we performed family-based whole exome sequencing of 23
      families including 25 patients with cerebellar and/or vermis atrophy in
      childhood, who were unable to be diagnosed solely by clinical examination.
      Pathological mutations of seven genes were found in ten patients from nine
      families (9/23, 39.1 %): compound heterozygous mutations in FOLR1, C5orf42, POLG,
      TPP1, PEX16, and de novo mutations in CACNA1A, and ITPR1. Patient 1A with FOLR1
      mutations showed extremely low concentration of 5-methyltetrahydrofolate in the
      cerebrospinal fluid and serum, and Patient 6 with TPP1 mutations demonstrated
      markedly lowered tripeptidyl peptidase 1 activity in leukocytes. Furthermore,
      Patient 8 with PEX16 mutations presented a mild increase of very long chain fatty
      acids in the serum as supportive data for genetic diagnosis. The main clinical
      features of these ten patients were nonspecific and mixed, and included
      developmental delay, intellectual disability, ataxia, hypotonia, and epilepsy.
      Brain MRI revealed both cerebellar and vermis atrophy in eight patients (8/10, 80
      %), vermis atrophy/hypoplasia in two patients (2/10, 20 %), and brainstem atrophy
      in one patient (1/10, 10 %). Our data clearly demonstrate the utility of whole
      exome sequencing for genetic diagnosis of childhood cerebellar and/or vermis
      atrophy. 

PMID- 24091542
TI  - "Occult" ovarian Leydig cell tumor: when laboratory tells more than imaging.
AB  - Hyperandrogenism is a common finding in premenopausal age and is generally caused
      by polycystic ovarian syndrome or other benign disease. Androgen-secreting tumors
      represent only 0.2 % of the causes of hyperandrogenism and usually present with
      severe clinical features, abrupt onset, and very high androgens levels. We
      describe here three cases of occult ovarian Leydig cell tumors suspected on the
      basis of severe clinical features of hyperandrogenism rapidly worsening, with
      elevated serum total testosterone levels, in which bilateral ovariectomy was
      performed and tumor was confirmed by post-operative histology. In all three
      cases, imaging was negative for ovarian tumor. Moreover, in one case the
      confounding concomitant finding of bilateral adrenal masses posed an additional
      challenge. Our experience highlights that testosterone levels represent the most
      helpful marker in the diagnosis of androgen-secreting ovarian tumor. In the
      absence of imaging findings, bilateral ovariectomy should be indicated, if
      supported by unequivocal clinical and laboratory data.

PMID- 24091543
TI  - Association of hematological parameters with metabolic syndrome in Beijing adult
      population: a longitudinal study.
AB  - The purposes of the study were to estimate the incidence of metabolic syndrome
      (MetS) and to systematically evaluate the relationship between hematological
      parameters and MetS in a 5-year follow-up of Beijing adult population. The
      longitudinal study included 3,180 adults, aged 20-65 years, who attended health
      check-ups in Beijing Tongren Hospital in 2007 and 2012. Multivariate logistic
      regression was conducted to explore the associations between hematological
      parameters and MetS. The 5-year cumulative incidence of MetS in this sample was
      10.82 % (14.22 % for males and 7.59 % for females). Among all the hematological
      parameters, white blood cell count (WBC) was positively associated with MetS for
      20-35-year-old (male OR 1.482, 95 % CI 1.169-2.974; female OR 1.398, 95 % CI
      1.145-3.011), and 36-50-year-old (male OR 2.012, 95 % CI 1.290-4.010; female OR
      3.400, 95 % CI 1.818-4.528) male and female subjects. Alanine aminotransferase
      (ALT) was significantly associated with the incidence of MetS for males (20-35
      year-old OR 2.080, 95 % CI 1.371-3.159; 36-50-year-old OR 2.421, 95 % CI 1.335
      3.412; 51-65-year-old OR 4.267, 95 % CI 1.161-6.781). Low-density lipoprotein
      cholesterol (LDL-C) was positively associated with MetS for 51-65-year-old (male
      OR 3.078, 95 % CI 2.468-5.131; female OR 2.140, 95 % CI 1.524-4.359) for male and
      female subjects. WBC is positively associated with MetS for young adults, while
      LDL-C is positively associated with MetS for elderly people. ALT is positively
      associated with MetS for males. Our findings provide further evidence in support
      of using hematological markers for early detection of individuals at risk for
      MetS.

PMID- 24091544
TI  - Identification of novel small molecule inhibitors of centrosome clustering in
      cancer cells.
AB  - Most normal cells have two centrosomes that form bipolar spindles during mitosis,
      while cancer cells often contain more than two, or "supernumerary" centrosomes.
      Such cancer cells achieve bipolar division by clustering their centrosomes into
      two functional poles, and inhibiting this process then leads to cancer-specific
      cell death. A major problem with clinically used anti-mitotic drugs, such as
      paclitaxel, is their toxicity in normal cells. To discover new compounds with
      greater specificity for cancer cells, we established a high-content screen for
      agents that block centrosome clustering in BT-549 cells, a breast cancer cell
      line that harbors supernumerary centrosomes. Using this screen, we identified 14
      compounds that inhibit centrosome clustering and induce mitotic arrest. Some of
      these compounds were structurally similar, suggesting a common structural motif
      important for preventing centrosome clustering. We next compared the effects of
      these compounds on the growth of several breast and other cancer cell lines, an
      immortalized normal human mammary epithelial cell line, and progenitor-enriched
      primary normal human mammary epithelial cells. From these comparisons, we found
      some compounds that kill breast cancer cells, but not their normal epithelial
      counterparts, suggesting their potential for targeted therapy. One of these
      compounds, N2-(3-pyridylmethyl)-5-nitro-2-furamide (Centrosome Clustering
      Chemical Inhibitor-01, CCCI-01), that showed the greatest differential response
      in this screen was confirmed to have selective effects on cancer as compared to
      normal breast progenitors using more precise apoptosis induction and clonogenic
      growth endpoints. The concentration of CCCI-01 that killed cancer cells in the
      clonogenic assay spared normal human bone marrow hematopoietic progenitors in the
      colony-forming cell assay, indicating a potential therapeutic window for CCCI-01,
      whose selectivity might be further improved by optimizing the compound.
      Immunofluorescence analysis showed that treatment with CCCI-01 lead to multipolar
      spindles in BT-549, while maintaining bipolar spindles in the normal primary
      human mammary epithelial cells. Since centrosome clustering is a complex process
      involving multiple pathways, the 14 compounds identified in this study provide a
      potentially novel means to developing non-cross-resistant anti-cancer drugs that
      block centrosome clustering. 

PMID- 24091545
TI  - Testicular hypoplasia in monochorionic dizygous twin with confined blood
      chimerism.

PMID- 24091546
TI  - Pneumothorax in women of child-bearing age: an update classification based on
      clinical and pathologic findings.
AB  - BACKGROUND: A significant percentage of pneumothorax in women is due to thoracic
      endometriosis. Pathophysiologic mechanisms continue to be debated, and pathologic
      aspects are poorly known. METHODS: Clinical and pathologic records of all
      consecutive women of reproductive age operated on for pneumothorax between 2000
      and 2011 were retrospectively reviewed. RESULTS: Two hundred twenty-nine women
      (mean age, 33 years) underwent surgery. One hundred forty-four cases (63%) were
      right-sided, and pneumothoraces were catamenial for 80 women (35%). Diagnosed
      pelvic endometriosis was associated in 29 cases. At pathology, thoracic
      endometriosis was diagnosed in 54 cases (24%). Endometrial glands were observed
      in 33 of 54 cases and were often cystic (16 of 33). Stroma was observed in 51 of
      54 cases and endometrial stroma without glands in 21 cases. Hemosiderin-laden
      macrophages were observed in 27 of 54 cases. All cases of thoracic endometriosis
      were positive for progesterone and/or estrogen receptors (intense and nuclear).
      Catamenial pneumothoraces (n = 80, 34.9%) were endometriosis related in 50% of
      cases (n = 40, 17% of the whole population). Pneumothoraces were noncatamenial
      but endometriosis related in 6% of cases (n = 14) and merely idiopathic in 60% of
      patients (n = 135). Multivariate analysis showed that right side, presence of
      diaphragmatic abnormalities, relapse after unilateral surgery, and presence of
      hemosiderin-laden macrophages were independent variables associated with thoracic
      endometriosis (all, P < .02). Apical emphysema-like changes were found in 184 of
      the 213 patients (86%) with apical resection and were significantly associated
      with the absence of thoracic endometriosis (P < .001). CONCLUSIONS: In women with
      surgically treated pneumothorax, prevalence of catamenial/endometriosis-related
      pneumothorax is high. Clinicians and pathologists must be aware to recognize such
      a difficult diagnosis.

PMID- 24091547
TI  - Why so secret?

PMID- 24091548
TI  - Working memory training may increase working memory capacity but not fluid
      intelligence.
AB  - Working memory is a critical element of complex cognition, particularly under
      conditions of distraction and interference. Measures of working memory capacity
      correlate positively with many measures of real-world cognition, including fluid
      intelligence. There have been numerous attempts to use training procedures to
      increase working memory capacity and thereby performance on the real-world tasks
      that rely on working memory capacity. In the study reported here, we demonstrated
      that training on complex working memory span tasks leads to improvement on
      similar tasks with different materials but that such training does not generalize
      to measures of fluid intelligence. 

PMID- 24091549
TI  - Synesthesia for color is linked to improved color perception but reduced motion
      perception.
AB  - Synesthesia is a rare condition in which one property of a stimulus (e.g., shape)
      triggers a secondary percept (e.g., color) not typically associated with the
      first. Work on synesthesia has predominantly focused on confirming the
      authenticity of synesthetic experience, but much less research has been conducted
      to examine the extent to which synesthesia is linked to broader perceptual
      differences. In the research reported here, we examined whether synesthesia is
      associated with differences in color and motion processing by comparing these
      abilities in synesthetes who experience color as their evoked sensation with
      nonsynesthetic participants. We show that synesthesia for color is linked to
      facilitated color sensitivity but decreased motion sensitivity. These findings
      are discussed in relation to the neurocognitive mechanisms of synesthesia and
      interactions between color and motion processing in typical adults. 

PMID- 24091550
TI  - Controlling intentions: the surprising ease of stopping after going relative to
      stopping after never having gone.
AB  - Decades of cognitive-control research have highlighted the difficulty of
      controlling a prepotent response. We examined whether having prepotent
      prospective-memory intentions similarly heightens the difficulty associated with
      stopping an intention once a prospective-memory task is finished. In three
      experiments, participants encoded a prospective-memory intention (e.g., press Q
      in response to the targets corn and dancer) and subsequently encountered either
      four targets or zero targets. Instructions then indicated that the prospective
      memory task was finished. In a follow-up task, the targets appeared, and
      commission errors were recorded. Surprisingly, it was easier for participants to
      stop the intention when it had been fulfilled (four-target condition) than when
      it had gone unfulfilled (zero-target condition; Experiments 1 and 2). This was
      true even after intention cancellation (Experiment 2). Although repeatedly
      performing an intention strengthens target-action links, it appears to enable
      deactivation of the intention, a process that is largely target specific
      (Experiment 3). We relate these findings to the Zeigarnik effect, target-action
      deactivation, and reconsolidation theories. 

PMID- 24091551
TI  - Highly selective sorption and unique packing geometries of unsaturated
      hydrocarbons and CO2 in a fluorine-substituted organic-inorganic ionic crystal.
AB  - An ionic crystal [Cr3O(OOCCF3)6(H2O)3]3[alpha-PW12O40].8CH3COCH3.8H2O.CHCl3 [Ia]
      was synthesized by the complexation of a fluorine-substituted macrocation with a
      phosphododecatungstate. Compound Ia possessed a layered structure with an
      interlayer distance of ca. 3.5 A, and the inner surface of the layer was
      decorated with CF3 groups of the macrocations. The solvent molecules (acetone and
      chloroform) spontaneously desorbed and exchanged with water under an ambient
      atmosphere and a hydrated phase [Cr3O(OOCCF3)6(H2O)3]3[alpha-PW12O40].25H2O [Ib]
      was formed. The water molecules were partially desorbed by the treatment of Ibin
      vacuo or under a dry N2 or He flow at 298-303 K, and [Cr3O(OOCCF3)6(H2O)3]3[alpha
      PW12O40].15H2O [Ic] was formed. The powder XRD pattern of Ic well agreed with
      that calculated for Ia, showing that the structure was maintained after the
      exchange and partial desorption of guests. Compound Ic sorbed CO2 and unsaturated
      hydrocarbons, while saturated hydrocarbons such as ethane and methane were almost
      excluded despite the similar kinetic diameters. Acetylene/methane, CO2/methane,
      and ethylene/ethane sorption ratios were 13, 15, and 4.9, respectively, at 198 K
      and 100 kPa. Typical Monte Carlo-based optimized geometries of acetylene and CO2
      showed different alignments in the structure of Ic despite the similar amounts of
      sorption and molecular sizes. Acetylene and CO2 were aligned mainly parallel and
      perpendicular, respectively, to the layer, which is probably due to the
      differences in the electron density distributions of the HOMO orbitals. 

PMID- 24091552
TI  - The prevalence of laparoscopy and patient safety outcomes: an analysis of
      colorectal resections.
AB  - BACKGROUND: Although laparoscopic colorectal surgery is associated with faster
      postoperative recovery and shorter hospital stays than open surgery,
      perioperative patient safety analyses using process-focused, validated measures
      have yet to be performed. METHODS: This study analyzed the U.S. Nationwide
      Inpatient Sample, a 20 % weighted sample of inpatient hospital discharges, from
      1998 to 2009. The study included patients who underwent open or laparoscopic
      colorectal resections and excluded those younger than 18 years and those who
      underwent emergent or multiple colorectal operations. The primary outcome measure
      was surgery-specific patient safety indicators (PSIs). Uni- and multivariate
      regression methods were used to estimate associations of surgery type with PSIs.
      RESULTS: A total of 2,936,641 patients were identified, and 177,547 (6 %) of
      these patients underwent laparoscopic colorectal resections. The laparoscopic
      patients were younger (p < 0.001) and more likely to be Caucasian (p = 0.005) and
      male (p < 0.001), to have lower Charlson scores (p < 0.001), and to undergo
      surgery in teaching hospitals (p < 0.001) located in urban areas (p < 0.001). The
      prevalence of laparoscopic surgery has increased rapidly in recent years, from 5
      to 29 % of all colorectal procedures performed in 2007 and 2009, respectively.
      The prevalence of any PSI was lower in the laparoscopic group (4.2 vs. 8.3 %; p <
      0.001). Multivariate analyses showed that the likelihood of any PSI for
      laparoscopic colorectal resection was 57 % lower than for open resections (odds
      ratio, 0.43; 95 % confidence interval, 0.40-0.46; p < 0.001). CONCLUSION:
      Laparoscopic colorectal surgery was associated with a lower risk of adverse
      patient safety events, a difference that became more pronounced as the prevalence
      of laparoscopy increased. Future studies should focus on factors that promote the
      safe adoption of innovative surgical techniques and optimize surgical outcomes.

PMID- 24091553
TI  - Single-incision laparoscopic appendectomy versus traditional three-port
      laparoscopic appendectomy: an analysis of outcomes at a single institution.
AB  - BACKGROUND: Questions have emerged as to whether single-incision laparoscopy has
      reproducible or superior patient outcomes compared with traditional laparoscopy.
      A retrospective review comparing single-incision laparoscopic (SILS) appendectomy
      and traditional multiport laparoscopic (MP) appendectomy was conducted to assess
      the safety and feasibility of the less invasive laparoscopic technique. METHODS:
      All SILS and MP appendectomies performed by three surgeons at a single
      institution during 43 months were reviewed. Statistical evaluation included
      descriptive analysis of demographic data including age and gender, as well as bi-
      and multi-variate analyses of operative outcomes including operative time,
      conversions, complications, and hospital length of stay. RESULTS: The study
      reviewed 168 patients who underwent SILS appendectomy and 108 patients who
      underwent MP appendectomy. No statistically significant difference was found
      between the mean SILS and MP operative times (43.63 vs. 40.95 min; p = 0.29).
      Additionally, no statistically significant association was noted between surgical
      approach and length of hospital stay. Although 0.93 % of MP appendectomies and
      2.38 % of SILS appendectomies were converted to open procedure, this difference
      was not statistically significant (p = 0.65, Fisher's exact test). After
      exclusion of cases converted to open procedure from the study, the findings
      showed that 3.66 % of SILS cases were converted to multiport laparoscopy. No
      increase in the overall complication rate was associated with SILS compared with
      MP appendectomy. The wound complications documented included one incisional
      hernia for SILS appendectomy and two wound infections for MP appendectomy.
      CONCLUSION: The findings showed SILS appendectomy to be a safe and feasible
      alternative to traditional MP appendectomy that can be conducted with operative
      times, lengths of stay, and complication rates similar to those of the
      standardized technique. This review is a precursor to prospective studies, which
      are warranted to demonstrate conclusively the equivalence of operative times,
      complications, and lengths of hospital stay, as well as to elucidate differences
      in patient-centered outcomes including postoperative pain, cosmesis, and quality
      of life.

PMID- 24091554
TI  - Has there been a paradigm shift in mediastinal surgery from open to minimally
      invasive, and from magnetic resonance imaging (MRI) to positron emission
      tomography-computerized tomography (PET-CT) in the last decade?
AB  - OBJECTIVE: The purpose of this study was to investigate the effects of diagnostic
      and surgical developments in the complete resection of the mediastinal masses.
      METHODS: Of 313 patients, 236 underwent therapeutic or diagnostic complete
      resections. We analyzed age, gender, diagnostic interventions, neoadjuvant
      treatment, type of surgical intervention (sternotomy, video-assisted thoracic
      surgery [VATS], thoracotomy), pathology, duration of hospital stay,
      complications, mortality, and associated diseases. Patients were divided into two
      groups according to the period of operation: group A included patients who were
      operated on between January 2002 and January 2007; group B included patients who
      were operated on between January 2007 and January 2012. RESULTS: Resection with
      VATS increased significantly after 2007, from 17.7 to 35 % (p = 0.03). The rate
      of complications increased after 2007 (p = 0.03), which was apparent in non-VATS
      patients (p = 0.03). The use of magnetic resonance imaging (MRI) decreased from
      29 to 15.5 % (p = 0.02) and positron emission tomography (PET)-computed
      tomography (CT) use increased from 1.6 to 25.2 % (p < 0.001). CONCLUSIONS: We
      identified a paradigm shift in mediastinal mass surgery. PET-CT became a more
      preferred diagnostic method and MRI became less preferred. The rate of VATS
      resection doubled and sternotomy decreased. Complication rates increased in non
      VATS due to an increase in extended resections.

PMID- 24091555
TI  - Site-specific chemical modification of antibody fragments using traceless
      cleavable linkers.
AB  - Antibody-drug conjugates (ADCs) are promising agents for the selective delivery
      of cytotoxic drugs to specific cells (for example, tumors). In this protocol, we
      describe two strategies for the precise modification at engineered C- or N
      terminal cysteines of antibodies in IgG, diabody and small immunoprotein (SIP)
      formats that yield homogenous ADCs. In this protocol, cemadotin derivatives are
      used as model drugs, as these agents have a potent cytotoxic activity and are
      easy to synthesize. However, other drugs with similar functional groups could be
      considered. In the first approach, a cemadotin derivative containing a sulfhydryl
      group results in a mixed disulfide linkage. In the second approach, a cemadotin
      derivative containing an aldehyde group is joined via a thiazolidine linkage. The
      procedures outlined are robust, enabling the preparation of ADCs with a defined
      number of drugs per antibody in a time frame between 7 and 24 h. 

PMID- 24091556
TI  - Quantification of free cysteines in membrane and soluble proteins using a
      fluorescent dye and thermal unfolding.
AB  - Cysteine is an extremely useful site for selective attachment of labels to
      proteins for many applications, including the study of protein structure in
      solution by electron paramagnetic resonance (EPR), fluorescence spectroscopy and
      medical imaging. The demand for quantitative data for these applications means
      that it is important to determine the extent of the cysteine labeling. The
      efficiency of labeling is sensitive to the 3D context of cysteine within the
      protein. Where the label or modification is not directly measurable by optical or
      magnetic spectroscopy, for example, in cysteine modification to dehydroalanine,
      assessing labeling efficiency is difficult. We describe a simple assay for
      determining the efficiency of modification of cysteine residues, which is based
      on an approach previously used to determine membrane protein stability. The assay
      involves a reaction between the thermally unfolded protein and a thiol-specific
      coumarin fluorophore that is only fluorescent upon conjugation with thiols.
      Monitoring fluorescence during thermal denaturation of the protein in the
      presence of the dye identifies the temperature at which the maximum fluorescence
      occurs; this temperature differs among proteins. Comparison of the fluorescence
      intensity at the identified temperature between modified, unmodified (positive
      control) and cysteine-less protein (negative control) allows for the
      quantification of free cysteine. We have quantified both site-directed spin
      labeling and dehydroalanine formation. The method relies on a commonly available
      fluorescence 96-well plate reader, which rapidly screens numerous samples within
      1.5 h and uses <100 MUg of material. The approach is robust for both soluble and
      detergent-solubilized membrane proteins. 

PMID- 24091557
TI  - In vitro sperm production from mouse spermatogonial stem cell lines using an
      organ culture method.
AB  - The in vitro propagation of mouse spermatogonial stem cells (SSCs) became
      possible in 2003; these cultured SSCs were named germ-line stem (GS) cells. To
      date, however, it has not been possible to induce spermatogenesis from GS cells
      in vitro. Recently, we succeeded in producing functional sperm from primitive
      spermatogonia in explanted neonatal mouse testis tissues. Here we describe a
      protocol that can support spermatogenesis from GS cells up to sperm formation in
      vitro using an organ culture method. GS cells transplanted in the extracted
      testis form colonies in the tissue fragments and differentiate into sperm under
      the described in vitro organ culture conditions. It takes about 6 weeks to obtain
      sperm from GS cells. The sperm are viable, resulting in healthy offspring through
      micro-insemination. Thus, this protocol should be a valuable tool for the study
      of mammalian spermatogenesis. 

PMID- 24091558
TI  - Prevalence of the petrified ear: a computed tomographic study.
AB  - The petrified ear is characterized by calcifications or ossifications of the
      cartilaginous parts of the outer ear. It is described as a rare finding, but the
      prevalence of this finding is unclear. In a retrospective analysis of 200
      computed tomographic scans of the head, 39 patients showed
      ossifications/calcifications of the cartilaginous parts of the outer ear (19.5%).
      These affected the cartilage of the auricle in 13 patients (6.5%), the
      cartilaginous parts of the external auditory channel in 25 (12.5%) and in one
      patient both (0.5%). All ossifications/calcifications were incidental findings in
      our series. Contrary to most authors, auricular ossifications/calcifications per
      se seem to be a common finding, but symptoms due to a petrified ear seem to be
      rare. To establish proper differential diagnosis, radiologists and
      otorhinolaryngologists should be aware of these findings.

PMID- 24091559
TI  - New diagnostic markers in salivary gland tumors.
AB  - Parotid gland tumors are a rare and heterogeneous entity. Molecular markers are
      sparse. The aim of the study was to identify new diagnostic markers in benign and
      malignant salivary tumors. A tissue microarray was constructed with 158 tumor
      samples. Expression of 21 tumor antigens involved in tumor cell survival and
      known for prognostic potential was assessed immunohistochemically in all parotid
      gland samples. CEA, Cox-1, Cox-2, Sigma, beta-Catenin, WISP-1 and PDGF-beta were
      differently regulated in benign and malignant parotid tumors. Subsequently, these
      seven proteins entered the step-wise logistic regression analysis. As a second
      step, we defined a score for differentiating benign versus malignant parotid
      lesions: 4*CEA+15*Cox-1+4*Cox-2+4*Sigma+3*PDGF-beta+10*beta-Catenin+14*Wisp1.
      Sensitivity and specificity of 94 and 83% were reached. Besides routine
      hematoxylin and eosin staining, definition of new diagnostic markers and
      subsequently a new diagnostic score are an attempt to create an additional tool
      for the diagnosis of parotid gland tumors.

PMID- 24091560
TI  - Tap water nasal irrigation in adults with seasonal allergic rhinitis: a
      randomized double-blind study.
AB  - Saline nasal irrigation is effective in the treatment of seasonal allergic
      rhinitis, and sodium chloride itself has no antiallergic effects. The mechanism
      of saline nasal irrigation depends mainly on washing away allergens and
      inflammatory mediators induced by allergic reactions. Tap water has the same
      washing effects as saline. In this study, it was investigated if tap water nasal
      irrigation was effective in the treatment of seasonal allergic rhinitis. Sixty
      four patients diagnosed with seasonal allergic rhinitis were enrolled. Patients
      were randomized to tap water nasal irrigation group and non-tap water nasal
      irrigation group for treatment. Patients of both groups were treated with
      desloratadine. Treatment outcomes were measured using allergic rhinitis Quality
      of Life (QoL) survey was completed at baseline and after 3 weeks of therapy.
      There were statistically significant differences in QoL scores between tap water
      nasal irrigation group and non-tap water nasal irrigation group. The tap water
      nasal irrigation group had better QoL scores than the non-tap water nasal
      irrigation group. Tap water nasal irrigation can be a valuable adjuvant therapy
      for patients with seasonal allergic rhinitis. 

PMID- 24091561
TI  - Newest Vital Sign as a proxy for medication adherence in older adults.
AB  - OBJECTIVE: To assess the utility of the Newest Vital Sign (NVS) as a proxy for
      medication adherence in community-dwelling older adults. DESIGN: Descriptive
      cross-sectional study. SETTING: 12 adult day care centers in the Lisbon
      metropolitan area, Portugal, between March and May 2009. PARTICIPANTS: 100 white
      community-dwelling older adults. INTERVENTION: Participants were administered the
      NVS, Single Item Literacy Screener (SILS), and self-reported Measure of Adherence
      to Therapy (MAT). MAIN OUTCOME MEASURES: Health literacy and medication
      adherence. RESULTS: The mean (+/-SD) age of the respondents was 73.3 +/- 7.8
      years and 71% were women. The NVS score was 0.81 +/- 0.10 (of 6 possible points),
      and 95% of the respondents scored in the three lowest possible scores, indicating
      a notable floor effect. Age was found to be inversely correlated with NVS score
      (P = 0.003). The MAT score was 36.2 +/- 4.7 (range 17-42). No statistically
      significant association between the NVS and level of education (P = 0.059
      [Kruskal-Wallis]), gender (P = 0.700 [Mann-Whitney]), SILS (P = 0.167), or MAT (P
      = 0.379) was identified. CONCLUSION: The utility of the NVS as a proxy for
      medication adherence in community-dwelling older adults is limited because of a
      floor effect that hinders its predictive power for medication adherence.

PMID- 24091562
TI  - What's love got to do with it: Relationship functioning and mental and physical
      quality of life among pregnant adolescent couples.
AB  - The study objective was to describe relationship adjustment and its association
      with mental and physical quality of life for young couples expecting a baby. 296
      young pregnant couples recruited from urban obstetric clinics reported on
      relationship strengths (e.g., equity, romantic love, and attractiveness),
      relationship risks (e.g., attachment, intimate partner violence), external family
      support, relationship adjustment, and mental and physical quality of life. Using
      the Actor Partner Interdependence Model we assessed both actor and partner
      effects of relationship variables on relationship adjustment and quality of life.
      Sixty-one percent of couples had at least one member with moderate or severe
      relationship distress. Lower attachment avoidance, lower attachment anxiety,
      higher relationship equity, lack of intimate partner violence, feelings of love,
      perceived partner attractiveness, and family support of the relationship related
      to better relationship adjustment. Associations were fairly consistent across
      gender. Better relationship adjustment related to more positive mental and
      physical quality of life for both young women and men. Our results highlight the
      potential importance of strong relationships on the well-being of expecting
      parents. Our results suggest that secure attachments, equitable relationships,
      feelings of love, and a lack of violence may be particularly important in having
      strong relationships and improved mental and physical health during pregnancy.

PMID- 24091563
TI  - Conjoint Community Resiliency Assessment Measure-28/10 items (CCRAM28 and
      CCRAM10): A self-report tool for assessing community resilience.
AB  - Community resilience is used to describe a community's ability to deal with
      crises or disruptions. The Conjoint Community Resiliency Assessment Measure
      (CCRAM) was developed in order to attain an integrated, multidimensional
      instrument for the measurement of community resiliency. The tool was developed
      using an inductive, exploratory, sequential mixed methods design. The objective
      of the present study was to portray and evaluate the CCRAM's psychometric
      features. A large community sample (N = 1,052) were assessed by the CCRAM tool,
      and the data was subjected to exploratory and confirmatory factor analysis. A
      Five factor model (21 items) was obtained, explaining 67.67 % of the variance.
      This scale was later reduced to 10-item brief instrument. Both scales showed good
      internal consistency coefficients (alpha = .92 and alpha = .85 respectively), and
      acceptable fit indices to the data. Seven additional items correspond to
      information requested by leaders, forming the CCRAM28. The CCRAM has been shown
      to be an acceptable practical tool for assessing community resilience. Both
      internal and external validity have been demonstrated, as all factors obtained in
      the factor analytical process, were tightly linked to previous literature on
      community resilience. The CCRAM facilitates the estimation of an overall
      community resiliency score but furthermore, it detects the strength of five
      important constructs of community function following disaster: Leadership,
      Collective Efficacy, Preparedness, Place Attachment and Social Trust.
      Consequently, the CCRAM can serve as an aid for community leaders to assess,
      monitor, and focus actions to enhance and restore community resilience for crisis
      situations.

PMID- 24091564
TI  - Long-term efficacy of electrical pudendal nerve stimulation for urgency-frequency
      syndrome in women.
AB  - INTRODUCTION AND HYPOTHESIS: Electrical pudendal nerve stimulation (EPNS) was
      developed by combining the advantages of pudendal neuromodulation (PNM) and
      percutaneous tibial nerve stimulation (PTNS) and incorporating the technique of
      deep insertion of long acupuncture needles. The purpose of this study is to show
      the long-term efficacy of EPNS in treating urgency-frequency syndrome (UFS) in
      women. METHODS: One hundred and six consecutive female UFS patients were enrolled
      and treated with EPNS. Long acupuncture needles were deeply inserted into four
      sacral points and electrified to stimulate the pudendal nerves. Evaluation of
      therapeutic effects was based on a questionnaire (including questions on storage,
      voiding, and postmicturition symptoms). Patients with >=50 % posttreatment
      symptom improvement were followed up for at least 60 months. RESULTS: Complete
      resolution and >=50 % improvement rate were 42.5 % and 85.8 %, respectively, in
      the 106 patients after a mean of 21.2 sessions of EPNS treatment. Of the 91
      patients with >=50 % posttreatment improvement, 62 (29 with complete resolution,
      15 with marked improvement, and 18 with moderate improvement) were available for
      follow-up at 60-126 (mean 99.5; median 98) months after the end of EPNS
      treatment. Of these 62 patients, 35 maintained the posttreatment effect, 18
      changed from better to complete resolution, and seven changed back to <50 %
      improvement; only four of whom changed to <25 % improvement. CONCLUSIONS: EPNS
      combines the advantages of PNM (better effect) and PTNS (minimally invasive,
      easily applicable, and well tolerated) in treating UFS. It has a good long-term
      therapeutic effect on UFS in women.

PMID- 24091565
TI  - Multi-morbidity, dependency, and frailty singly or in combination have different
      impact on health outcomes.
AB  - Multi-morbidity, dependency, and frailty were studied simultaneously in a
      community-living cohort of 4,000 men and women aged 65 years and over to examine
      the independent and combined effects on four health outcomes (mortality, decline
      in physical function, depression, and polypharmacy). The influence of
      socioeconomic status on these relationships is also examined. Mortality data was
      documented after a mean follow-up period of 9 years, while other health outcomes
      were documented after 4 years of follow-up. Fifteen percent of the cohort did not
      have any of these syndromes. Of the remaining participants, nearly one third had
      multi-morbidity and frailty (pre-frail and frail), while all three syndromes were
      present in 11 %. All syndromes as well as socioeconomic status were significantly
      associated with all health outcomes. Mortality was only increased for age, being
      male, frailty status, and combinations of syndromes that included frailty. Both
      multi-morbidity and frailtymale was protective. Only a combination of all three
      syndromes, and age per se, increased the risk of depressive symptoms at 4 years
      while being male conferred reduced risk. Multi-morbidity, but not frailty status
      or dependency, and all syndrome combinations that included multi-morbidity were
      associated with use of >= four medications. Decline in homeostatic function with
      age may thus be quantified and taken into account in prediction of various health
      outcomes, with a view to prevention, management, formulation of guidelines,
      service planning, and the conduct of randomized controlled trials of
      interventions or treatment. 

PMID- 24091566
TI  - HER4 expression status correlates with improved outcome in both neoadjuvant and
      adjuvant Trastuzumab treated invasive breast carcinoma.
AB  - Prognostic and predictive markers utilized in invasive breast carcinoma are
      limited and include ER, PR, Ki67, and ERBB2 (HER2). In the case of HER2, over
      expression or amplification serves as eligibility for anti-HER2 based therapy,
      including trastuzumab (Herceptin(r), Genentech). While clinical trials have shown
      trastuzumab improves overall survival and time to progression, an individual's
      response to anti-HER2 based therapy is highly variable. This suggests that, in a
      "uniform" HER2 positive population, additional markers could help in predicting
      patient outcome to therapy. Here we utilized a recently validated high
      specificity HER4 antibody (E200) and generated a standard clinical HER4 scoring
      algorithm (HER4 H-Score) utilizing two breast carcinoma cohorts: 1) patients
      receiving neoadjuvant trastuzumab (n=47) and 2) patients receiving trastuzumab
      for metastatic disease (n=33). Our HER4 H-Score showed significant correlation
      with high sensitivity RT-qPCR performed on matched patients (p=<0.0001). In
      addition, patients with HER2/HER4 co-over-expression status showed a significant
      delay in development of metastasis after neo-adjuvant trastuzumab therapy (p=
      0.04) and showed a significant improvement in progression free survival after
      adjuvant trastuzumab therapy (p=0.03). These findings suggest HER4 IHC, used in
      conjunction with a standard HER2 testing algorithm, could aid in predicting
      clinical outcome and help identify patients likely to show improved response to
      trastuzumab therapy. 

PMID- 24091568
TI  - Recent advances in surface chemistry strategies for the fabrication of functional
      iron oxide based magnetic nanoparticles.
AB  - The synthesis of superparamagnetic nanostructures, especially iron-oxide based
      nanoparticles (IONPs), with appropriate surface functional groups has been
      intensively researched for many high-technological applications, including high
      density data storage, biosensing and biomedicine. In medicine, IONPs are nowadays
      widely used as contrast agents for magnetic resonance imaging (MRI), in
      hyperthermia therapy, but are also exploited for drug and gene delivery,
      detoxification of biological fluids or immunoassays, as they are relatively non
      toxic. The use of magnetic particles in vivo requires IONPs to have high
      magnetization values, diameters below 100 nm with overall narrow size
      distribution and long time stability in biological fluids. Due to the high
      surface energies of IONPs agglomeration over time is often encountered. It is
      thus of prime importance to modify their surface to prevent aggregation and to
      limit non-specific adsorption of biomolecules onto their surface. Such chemical
      modifications result in IONPs being well-dispersed and biocompatible, and allow
      for targeted delivery and specific interactions. The chemical nature of IONPs
      thus determines not only the overall size of the colloid, but also plays a
      significant role for in vivo and in vitro applications. This review discusses the
      different concepts currently used for the surface functionalization and coating
      of iron oxide nanoparticles. The diverse strategies for the covalent linking of
      drugs, proteins, enzymes, antibodies, and nucleotides will be discussed and the
      chemically relevant steps will be explained in detail. 

PMID- 24091567
TI  - A validated risk model to predict 90-day VTE events in postsurgical patients.
AB  - BACKGROUND: VTE is the proximate cause of 100,000 deaths in the United States
      each year. Perioperative VTE risk among surgical patients varies by 20-fold,
      which highlights the importance of risk stratification to identify high-risk
      patients, in whom chemoprophylaxis can decrease VTE risk, and low-risk patients,
      for whom the risk-benefit relationship of prophylaxis may be unfavorable.
      METHODS: We used data from a statewide surgical quality collaborative for
      surgical procedures performed between 2010 and 2012. Regression-based techniques
      identified predictors of 90-day VTE while adjusting for procedural complexity and
      comorbid conditions. A weighted risk index was created and was validated
      subsequently in a separate, independent dataset. RESULTS: Data were available for
      10,344 patients, who were allocated randomly to a derivation or validation
      cohort. The 90-day VTE rate was 1.4%; 66.2% of the derivation cohort and 65.5% of
      the validation cohort received chemoprophylaxis. Seven risk factors were
      incorporated into a weighted risk index: personal history of VTE, current cancer,
      sepsis/septic shock/systemic inflammatory response syndrome, age>=60 years,
      BMI>=40 kg/m2, male sex, and family history of VTE. Prediction for 90-day VTE was
      similar in the derivation and validation cohorts (areas under the receiver
      operator curve, 0.72 and 0.70, respectively). An 18-fold variation in 90-day VTE
      rate was identified. CONCLUSIONS: A weighted risk index quantifies 90-day VTE
      risk among surgical patients and identifies an 18-fold variation in VTE risk
      among the overall surgical population.

PMID- 24091585
TI  - Abnormal cardiac enzymes in systemic sclerosis: a report of four patients and
      review of the literature.
AB  - Cardiac involvement in systemic sclerosis (SSc) is heterogeneous and can include
      primary involvement of the myocardium, pericardium and coronary arteries or be
      secondary to cardiac complications of pulmonary and renal disease. Primary
      cardiac involvement in SSc is uncommon but can result in ventricular dysfunction,
      organ failure, arrhythmias and death. It can remain clinically silent and the
      prevalence is likely to be under-reported. We report four cases of SSc associated
      with a raised serum troponin T (TnT), in a proportion of whom cardiac MRI
      myocardial abnormalities were detected. These cases highlight the heterogeneity
      of cardiac involvement in SSc, the role of cardiac MRI and promising biochemical
      responses to immunosuppression. Cardiac biomarkers such as TnT may be useful
      screening tools to identify subclinical cardiac disease and assess response to
      therapeutic intervention. 

PMID- 24091586
TI  - Interactions between spatially explicit conservation and management measures:
      implications for the governance of marine protected areas.
AB  - Marine protected areas are not established in an institutional and governance
      vacuum and managers should pay attention to the wider social-ecological system in
      which they are immersed. This article examines Islas Choros-Damas Marine Reserve,
      a small marine protected area located in a highly productive and biologically
      diverse coastal marine ecosystem in northern Chile, and the interactions between
      human, institutional, and ecological dimensions beyond those existing within its
      boundaries. Through documents analysis, surveys, and interviews, we described
      marine reserve implementation (governing system) and the social and natural
      ecosystem-to-be-governed. We analyzed the interactions and the connections
      between the marine reserve and other spatially explicit conservation and/or
      management measures existing in the area and influencing management outcomes and
      governance. A top-down approach with poor stakeholder involvement characterized
      the implementation process. The marine reserve is highly connected with other
      spatially explicit measures and with a wider social-ecological system through
      various ecological processes and socio-economic interactions. Current
      institutional interactions with positive effects on the management and governance
      are scarce, although several potential interactions may be developed. For the
      study area, any management action must recognize interferences from outside
      conditions and consider some of them (e.g., ecotourism management) as cross
      cutting actions for the entire social-ecological system. We consider that
      institutional interactions and the development of social networks are
      opportunities to any collective effort aiming to improve governance of Islas
      Choros-Damas marine reserve. Communication of connections and interactions
      between marine protected areas and the wider social-ecological system (as
      described in this study) is proposed as a strategy to improve stakeholder
      participation in Chilean marine protected areas. 

PMID- 24091587
TI  - Assessing degradation of abandoned farmlands for conservation of the Monte Desert
      biome in Argentina.
AB  - Land abandonment is a major issue worldwide. In Argentina, the Monte Desert is
      the most arid rangeland, where the traditional conservation practices are based
      on successional management of areas excluded to disturbances or abandoned. Some
      areas subjected to this kind of management may be too degraded, and thus require
      active restoration. Therefore, the aim of this study was to assess whether
      passive succession-based management is a suitable approach by evaluating the
      status of land degradation in a protected area after 17-41 years of farming
      abandonment. Soil traits and plant growth forms were quantified and compared
      between sites according to time since abandonment and former land use
      (cultivation and grazing). Two variables were calculated using the CORINE-CEC
      method, i.e., potential (PSER) and actual (ASER) soil erosion risk. PSER
      indicates the erosion risk when no vegetation is present, while ASER includes the
      protective role of vegetation cover. Results showed that land use history had no
      significant effect on plant growth forms or soil traits (p > 0.05). After more
      than 25 years since abandonment of farming activities, soil conditions and
      vegetation cover had improved, thus having a lower ASER. Nevertheless, the
      present soil physical crusts may have delayed the full development of vegetation,
      enhancing erosion processes. Overall, this study indicates that succession-based
      management may not be the best practice in terms of conservation. Therefore, any
      effort for conservation in the Monte Desert should contemplate the current status
      of land degradation and potential vegetation recovery.

PMID- 24091588
TI  - Letter from the editor.

PMID- 24091590
TI  - Portrait of a leader in immunotherapeutics.
AB  - It's the question that every grade school kid has to answer at some point or
      another--"What do you want to be when you grow up?" My mom still has the second
      grade paper on which I first wrote down that I wanted to be a "physician
      scientist." I'm quite certain that I probably didn't know exactly what a
      physician scientist was at the time. I certainly didn't know any physician
      scientists personally, nor was I exposed to academic environments in the tiny
      Minnesota town in which I grew up. All I'm certain of, was at that time, I liked
      reading about science. Unfortunately, I soon came to know the medical profession
      all too personally.

PMID- 24091591
TI  - How cognitive plasticity resolves the brain's information processing dilemma.
AB  - A key unresolved question in cognitive science is whether the brain uses
      asynchronous or synchronous patterns of information transmission. Using an
      auditory learning task combined with electrophysiological recordings, we reveal
      for the first time that cognitive plasticity during learning transforms an
      asynchronous into a synchronous transmission pattern to achieve rapid, error-free
      performance. We also present a new model showing how the brain may resolve its
      information processing and transmission dilemma. 

PMID- 24091592
TI  - Theoretical studies of electronic structures, magnetic properties and electron
      conductivities of one-dimensional Ni(n) (n = 3, 5, 7) complexes.
AB  - Electronic structures, magnetic properties and electron conductivities of
      linearly aligned one-dimensional (1-D) Ni(II)3, Ni(II)5 and Ni(II)7 complexes,
      i.e. [Ni3(dpa)4NCS2], [Ni5(tpda)4X2] (X = Cl, CN, N3, NCS) and [Ni7(teptra)4Cl2],
      are systematically investigated by the broken-symmetry B3LYP calculations and
      simulations based on an elastic scattering Green's function theory. Calculated
      spin densities appear only at terminal Ni ions, while inner Ni ions are the
      closed-shell. The calculated effective exchange integrals (J(ab)) values
      reproduce well the experimental results that indicate anti-ferromagnetic (AF)
      interactions between two terminal Ni ions. Natural orbitals and their occupation
      numbers show that a change in the weak AF couplings by axial ligands in penta
      nickel complexes originates in sigma-type orbitals. Simulated electron
      conductivities of [Ni3(dpa)4NCS2] and [Ni5(tpda)4NCS2] semi-quantitatively
      correspond to the experimental results. By the analyses, it is elucidated that
      electrons are mainly transmitted by sigma-type orbitals, but the bonds between Au
      and axial ligands are also dominant factors for conductivity.

PMID- 24091594
TI  - The non-interventional BonViva Intravenous Versus Alendronate (VIVA) study: real
      world adherence and persistence to medication, efficacy, and safety, in patients
      with postmenopausal osteoporosis.
AB  - Adherence and persistence to oral bisphosphonates in women with postmenopausal
      osteoporosis is suboptimal. In this study, patients were treated with either oral
      or intravenous bisphosphonates. The increased adherence and persistence observed
      in patients receiving intravenous medication compared with those receiving oral
      medication may improve health outcomes. INTRODUCTION: Poor adherence and
      persistence to oral medication are often observed in women with postmenopausal
      osteoporosis (PMO). The purpose of the non-interventional BonViva Intravenous
      Versus Alendronate (VIVA) study was to determine whether, in a real-world
      setting, (1) increased adherence and persistence to medication would be observed
      in women with PMO receiving intravenous (i.v.) ibandronate versus oral
      alendronate, (2) a correlation exists between adherence and persistence to
      medication and drug efficacy, and (3) any unexpected adverse events/serious
      adverse events (AEs/SAEs) may occur. METHODS: The study was conducted in 632
      centers in Germany. A total of 6,064 females with PMO were enrolled and recruited
      into one of two treatment arms: quarterly i.v. administration of 3 mg ibandronate
      or weekly oral medication of 70 mg alendronate, for 12 months. At the end of the
      study, adherence and persistence to medication, new osteoporotic fractures,
      mobility, use of analgesics, and AEs/SAEs were determined. RESULTS: Greater
      adherence and persistence to medication were observed in the ibandronate
      treatment arm compared with the alendronate treatment arm. Although there was no
      significant difference in the number of patients with new vertebral, hip, or
      forearm fractures between treatment arms, a significantly greater increase in
      mobility and decrease in the use of analgesics were reported in the ibandronate
      treatment arm. No unexpected AEs/SAEs occurred in either arm. CONCLUSIONS:
      Adherence and persistence to medication were greater in women with PMO receiving
      i.v. ibandronate compared with those receiving oral alendronate. This may have
      led to an increase in mobility and a decrease in pain in these patients.

PMID- 24091593
TI  - Neuropathy and the vascular-bone axis in diabetes: lessons from Charcot
      osteoarthropathy.
AB  - Emerging evidence from the last two decades has shown that vascular calcification
      (VC) is a regulated, cell-mediated process orchestrated by vascular smooth muscle
      cells (VSMCs) and that this process bears many similarities to bone
      mineralization. While many of the mechanisms driving VSMC calcification have been
      well established, it remains unclear what factors in specific disease states act
      to promote vascular calcification and in parallel, bone loss. Diabetes is a
      condition most commonly associated with VC and bone abnormalities. In this
      review, we describe how factors associated with the diabetic milieu impact on
      VSMCs, focusing on the role of oxidative stress, inflammation, impairment of the
      advanced glycation end product (AGE)/receptor for AGE system and, importantly,
      diabetic neuropathy. We also explore the link between bone and VC in diabetes
      with a specific emphasis on the receptor activator of nuclear factor kappabeta
      ligand/osteoprotegerin system. Finally, we describe what insights can be gleaned
      from studying Charcot osteoarthropathy, a rare complication of diabetic
      neuropathy, in which the occurrence of VC is frequent and where bone lysis is
      extreme. 

PMID- 24091595
TI  - Intravenous fish oil lipid emulsion promotes a shift toward anti-inflammatory
      proresolving lipid mediators.
AB  - Parenteral nutrition (PN)-associated liver disease (PNALD) is a life-threatening
      complication of the administration of PN. The development of PNALD may be partly
      due to the composition of the lipid emulsion administered with PN: soybean oil
      based lipid emulsions (SOLE) are associated with liver disease, while fish oil
      based lipid emulsions (FOLE) are associated with prevention and improvement of
      liver disease. The objective of this study was to determine how the choice of
      lipid emulsion modified the production of bioactive lipid mediators (LMs). We
      utilized a mouse model of steatosis to study the differential effect of FOLE and
      SOLE. We subsequently validated these results in serum samples from a small
      cohort of human infants transitioning from SOLE to FOLE. In mice, FOLE was
      associated with production of anti-inflammatory, proresolving LMs; SOLE was
      associated with increased production of inflammatory LMs. In human infants, the
      transition from SOLE to FOLE was associated with a shift toward a proresolving
      lipidome. Together, these results demonstrate that the composition of the lipid
      emulsion directly modifies inflammatory homeostasis. 

PMID- 24091597
TI  - Reduced funding and sequestration impact young biomedical researchers.

PMID- 24091596
TI  - HMGB1 recruits hepatic stellate cells and liver endothelial cells to sites of
      ethanol-induced parenchymal cell injury.
AB  - Hepatic stellate cells (HSC) and liver endothelial cells (LEC) migrate to sites
      of injury and perpetuate alcohol-induced liver injury. High-mobility group box 1
      (HMGB1) is a protein released from the nucleus of injured cells that has been
      implicated as a proinflammatory mediator. We hypothesized that HMGB1 may be
      released from ethanol-stimulated liver parenchymal cells and contribute to HSC
      and LEC recruitment. Ethanol stimulation of rat hepatocytes and HepG2 cells
      resulted in translocation of HMGB1 from the nucleus as assessed by Western blot.
      HMGB1 protein levels were increased in the supernatant of ethanol-treated
      hepatocytes compared with vehicle-treated cells. Migration of both HSC and LEC
      was increased in response to conditioned medium for ethanol-stimulated
      hepatocytes (CMEtOH) compared with vehicle-stimulated hepatocytes (CMVEH) (P <
      0.05). However, the effect of CMEtOH on migration was almost entirely reversed by
      treatment with HMGB1-neutralizing antibody or when HepG2 cells were
      pretransfected with HMGB1-siRNA compared with control siRNA-transfected HepG2
      cells (P < 0.05). Recombinant HMGB1 (100 ng/ml) also stimulated migration of HSC
      and LEC compared with vehicle stimulation (P < 0.05 for both HSC and LEC). HMGB1
      stimulation of HSC increased the phosphorylation of Src and Erk and HMGB1-induced
      HSC migration was blocked by the Src inhibitor PP2 and the Erk inhibitor U0126.
      Hepatocytes release HMGB1 in response to ethanol with subsequent recruitment of
      HSC and LEC. This pathway has implications for HSC and LEC recruitment to sites
      of ethanol-induced liver injury. 

PMID- 24091598
TI  - Ezrin regulates the expression of Mrp2/Abcc2 and Mdr1/Abcb1 along the rat small
      intestinal tract.
AB  - Multidrug resistance-associated protein 2 (MRP2)/ATP-binding cassette protein C2
      (ABCC2) and multidrug resistance protein 1 (MDR1)/ABCB1 are well-known efflux
      transporters located on the brush border membrane of the small intestinal
      epithelia, where they limit the absorption of a broad range of substrates. The
      expression patterns of MRP2/ABCC2 and MDR1/ABCB1 along the small intestinal tract
      are tightly regulated. Several reports have demonstrated the participation of ERM
      (ezrin/radixin/moesin) proteins in the posttranslational modulation of MRP2/ABCC2
      and MDR1/ABCB1, especially with regard to their membrane localization. The
      present study focused on the in vivo expression profiles of MRP2/ABCC2,
      MDR1/ABCB1, ezrin, and phosphorylated ezrin to further elucidate the relationship
      between the efflux transporters and the ERM proteins. The current results showed
      good correlation between the phosphorylation status of ezrin and Mrp2/Abcc2
      expression along the gastrointestinal tract of rats and between the expression
      profiles of both ezrin and Mdr1/Abcb1 in the small intestine. We also
      demonstrated the involvement of conventional protein kinase C isoforms in the
      regulation of ezrin phosphorylation. Furthermore, experiments conducted with wild
      type (WT) ezrin and a T567A (Ala substituted Thr) dephosphorylated mutant showed
      a decrease in membrane surface-localized and total expressed MRP2/ABCC2 in T567A
      expressing vs. WT ezrin-expressing Caco-2 cells. In contrast, T567A- and WT
      expressing cells both showed an increase in membrane surface-localized and total
      expressed MDR1/ABCB1. These findings suggest that the phosphorylation status and
      the expression profile of ezrin differentially direct MRP2/ABCC2 and MDR1/ABCB1
      expression, respectively, along the small intestinal tract.

PMID- 24091599
TI  - Reduced hepatic mitochondrial respiration following acute high-fat diet is
      prevented by PGC-1alpha overexpression.
AB  - Changes in substrate utilization and reduced mitochondrial respiratory capacity
      following exposure to energy-dense, high-fat diets (HFD) are putatively key
      components in the development of obesity-related metabolic disease. We examined
      the effect of a 3-day HFD on isolated liver mitochondrial respiration and whole
      body energy utilization in obesity-prone (OP) rats. We also examined if hepatic
      overexpression of peroxisomal proliferator-activated receptor-gamma coactivator
      1alpha (PGC-1alpha), a master regulator of mitochondrial respiratory capacity and
      biogenesis, would modify liver and whole body responses to the HFD. Acute, 3-day
      HFD (45% kcal) in OP rats resulted in increased daily energy intake, energy
      balance, weight gain, and adiposity, without an increase in liver triglyceride
      (triacylglycerol) accumulation. HFD-fed OP rats also displayed decreased whole
      body substrate switching from the dark to the light cycle, which was paired with
      reductions in hepatic mitochondrial respiration of multiple substrates in
      multiple respiratory states. Hepatic PGC-1alpha overexpression was observed to
      protect whole body substrate switching, as well as maintain mitochondrial
      respiration, following the acute HFD. Additionally, liver PGC-1alpha
      overexpression did not alter whole body dietary fatty acid oxidation but resulted
      in greater storage of dietary free fatty acids in liver lipid, primarily as
      triacylglycerol. Together, these data demonstrate that a short-term HFD can
      result in a decrease in metabolic flexibility and hepatic mitochondrial
      respiratory capacity in OP rats that is completely prevented by hepatic
      overexpression of PGC-1alpha. 

PMID- 24091600
TI  - Mechanisms of STAT3 activation in the liver of FXR knockout mice.
AB  - Farnesoid X receptor (FXR, Nr1h4) is a ligand-activated transcription factor
      belonging to the nuclear receptor superfamily. FXR is essential in maintaining
      bile acid (BA) homeostasis, and FXR(-/-) mice develop cholestasis, inflammation,
      and spontaneous liver tumors. The signal transducer and activator of
      transcription 3 (STAT3) is well known to regulate liver growth, and STAT3 is
      feedback inhibited by its target gene, the suppressor of cytokine signaling 3
      (SOCS3). Strong activation of STAT3 was detected in FXR(-/-) mouse livers.
      However, the mechanism of STAT3 activation with FXR deficiency remains elusive.
      Wild-type (WT) and FXR(-/-) mice were used to detect STAT3 pathway activation in
      the liver. In vivo BA feeding or deprivation was used to determine the role of
      BAs in STAT3 activation, and in vitro molecular approaches were used to determine
      the direct transcriptional regulation of SOCS3 by FXR. STAT3 was activated in
      FXR(-/-) but not WT mice. BA feeding increased, but deprivation by cholestyramine
      reduced, serum inflammatory markers and STAT3 activation. Furthermore, the Socs3
      gene was determined as a direct FXR target gene. The elevated BAs and
      inflammation, along with reduced SOCS3, collectively contribute to the activation
      of the STAT3 signaling pathway in the liver of FXR(-/-) mice. This study suggests
      that the constitutive activation of STAT3 may be a mechanism of liver
      carcinogenesis in FXR(-/-) mice. 

PMID- 24091602
TI  - Selected topics of the DGPPN Congress 2012.

PMID- 24091601
TI  - The role of mediators of cell invasiveness, motility, and migration in the
      pathogenesis of silent corticotroph adenomas.
AB  - Silent corticotroph adenomas (SCAs) represent a distinct subset of clinically non
      functioning pituitary adenomas. There are two variants of SCA; type I are densely
      granulated basophilic tumors and type II are sparsely granulated and chromophobic
      tumors. SCAs are known to be aggressive than the more common non-functioning
      gonadotroph adenomas (NFGAs). Cell-matrix interactions play an important role in
      the pathogenesis of pituitary adenomas. In this study, we compared 19 SCAs and 50
      NFGAs with known fibroblast growth factor receptor-4 (FGFR4) status using semi
      quantitative immunohistochemistry to localize beta1-integrin, osteopontin, and
      matrix metalloproteinase-1 (MMP-1) as cytoplasmic, membranous, or mixed
      cytoplasmic-membranous staining to achieve scores of 1-4. Staining for beta1
      integrin was significantly higher in SCAs (100 %, score 3.3) than in NFGAs (96 %;
      score 2.6) (p = 0.0482); there was no statistical difference within subgroups of
      SCA (type II score 3.4; type I score 2.8) (p = 0.2663). Osteopontin
      immunoreactivity was also higher in SCAs (100 %, score 3.7) than in NFGAs (42 %,
      score 0.8) (p = 0.0001); there was no statistical difference within subgroups of
      SCA (type II score 3.6; type I score 3.9) (p = 0.2787). In contrast, MMP-1
      immunoreactivity was lower in SCAs (89 %; score 2.5) than in NFGAs (98 %; score
      3.6) (p = 0.0005); there was no statistical difference within subgroups of SCA
      (type II score 2.7; type I score 2.0) (p = 0.30704). The MMP-1 results correlated
      with FGFR4 expression (NFGA 96 %, type II SCA 71 %, type I SCA 40 %). Our data
      indicate that the biological aggressivity of SCAs compared with NFGA may be due
      to high osteopontin expression; in contrast, high MMP-1 is characteristic of
      NFGAs that also express more FGFR4. Further investigations are warranted to
      clarify the underlying regulatory mechanisms of these markers. The high
      osteopontin or FGFR4/MMP-1 expression levels in SCAs and NFGAs, respectively,
      indicate the potential for therapeutic strategies targeting osteopontin or
      FGFR4/MMP-1 for inoperable tumors of these types. 

PMID- 24091603
TI  - Sport specificity of mental disorders: the issue of sport psychiatry.
AB  - The prevalence of psychiatric conditions among elite athletes is still under
      debate. More and more evidence has accumulated that high-performance athletes are
      not protected from mental disorders as previously thought. The authors discuss
      the issue of the sport specificity of selected mental diseases in elite athletes.
      Specific aspects of eating disorders, exercise addiction, chronic traumatic
      encephalopathy and mood disorders in the context of overtraining syndrome are
      examined. In particular, the interrelationship between life and work
      characteristics unique to elite athletes and the development of mental disorders
      are reviewed. Differences of clinical presentation and some therapeutic
      consequences are discussed. The authors suggest that the physical and mental
      strains endured by elite athletes might influence the onset and severity of their
      psychiatric disorder. Beside the existing research strategies dealing with the
      amount of exercise, its intensity and lack of recreation experienced by athletes,
      further research on psycho-social factors is needed to better understand the
      sport-specific aetiology of mental disorders in high-performance athletes. 

PMID- 24091604
TI  - Streptomyces fukangensis sp. nov., a novel alkaliphilic actinomycete isolated
      from a saline-alkaline soil.
AB  - An alkaliphilic actinobacterium, designated EGI 80050(T), was isolated from a
      desert soil sample of Xinjiang, north-west China, and characterized by a
      polyphasic approach. The isolate was observed to produce purple orange-yellow
      aerial mycelium and dark orange-yellow substrate mycelium on yeast extract-malt
      extract agar medium. Whole-cell hydrolysates of strain EGI 80050(T) were found to
      contain LL-diaminopimelic acid as the diagnostic diamino acid, and galactose,
      glucose, rhamnose and mannose as the main sugars. The major fatty acids
      identified were C16:0-iso (36.8 %), C15:0-anteiso (17.3 %), 15:0-iso (13.2 %) and
      14:0-iso (10.5 %). The predominant menaquinones detected were MK-9(H6) and MK
      9(H8), while the characteristic polar lipids were identified as
      diphosphatidylglycerol, phosphatidylglycerol, phosphatidylinositol,
      phosphatidylinositol mannosides, phosphatidylmethylethanolamine and three unknown
      phospholipids. The G+C content of the genomic DNA was determined to be 67.9 mol%.
      Phylogenetic analysis based on 16S rRNA gene sequences affiliated the strain EGI
      80050(T) to the genus Streptomyces. Levels of 16 rRNA gene sequence similarities
      between strain EGI 80050(T) and Streptomyces candidus NRRL ISP-5141(T),
      Streptomyces cremeus NBRC 12760(T), Streptomyces spiroverticillatus NBRC
      12821(T), Streptomyces violaceorectus NBRC 13102(T), Streptomyces cinereoruber
      subsp. cinereoruber NBRC 12756(T) were 96.7, 96.6, 96.6, 96.6 and 96.6 %,
      respectively. Based on the phenotypic, chemotaxonomic and phylogenetic data,
      strain EGI 80050(T) is considered to represent a novel species of the genus
      Streptomyces, for which the name Streptomyces fukangensis sp. nov. (type strain
      EGI 80050(T) = BCRC 16945(T) = JCM 19127(T)) is proposed.

PMID- 24091605
TI  - Lung cancer tumorigenicity and drug resistance are maintained through
      ALDH(hi)CD44(hi) tumor initiating cells.
AB  - Limited improvement in long term survival of lung cancer patients has been
      achieved by conventional chemotherapy or targeted therapy. To explore the
      potentials of tumor initiating cells (TIC)-directed therapy, it is essential to
      identify the cell targets and understand their maintenance mechanisms. We have
      analyzed the performance of ALDH/CD44 co-expression as TIC markers and treatment
      targets of lung cancer using well-validated in vitro and in vivo analyses in
      multiple established and patient-derived lung cancer cells. The ALDH(hi)CD44(hi)
      subset showed the highest enhancement of stem cell phenotypic properties compared
      to ALDH(hi)CD44(lo), ALDH(lo)CD44(hi), ALDH(lo)CD44(lo) cells and unsorted
      controls. They showed higher invasion capacities, pluripotency genes and
      epithelial-mesenchymal transition transcription factors expression, lower
      intercellular adhesion protein expression and higher G2/M phase cell cycle
      fraction. In immunosuppressed mice, the ALDH(hi)CD44(hi)xenografts showed the
      highest tumor induction frequency, serial transplantability, shortest latency,
      largest volume and highest growth rates. Inhibition of sonic Hedgehog and Notch
      developmental pathways reduced ALDH+CD44+ compartment. Chemotherapy and targeted
      therapy resulted in higher AALDH(hi)CD44(hi) subset viability and
      ALDH(lo)CD44(lo) subset apoptosis fraction. ALDH inhibition and CD44 knockdown
      led to reduced stemness gene expression and sensitization to drug treatment. In
      accordance, clinical lung cancers containing a higher abundance of ALDH and CD44
      coexpressing cells was associated with lower recurrence-free survival. Together,
      results suggested theALDH(hi)CD44(hi)compartment was the cellular mediator of
      tumorigenicity and drug resistance. Further investigation of the regulatory
      mechanisms underlying ALDH(hi)CD44(hi)TIC maintenance would be beneficial for the
      development of long term lung cancer control.

PMID- 24091606
TI  - Differences in disease expression between primary ciliary dyskinesia and cystic
      fibrosis with and without pancreatic insufficiency.
AB  - BACKGROUND: Impaired mucociliary clearance causes pulmonary disease in primary
      ciliary dyskinesia (PCD) and contributes to cystic fibrosis (CF) lung disease.
      Although the sinopulmonary disease is similar, morbidity and mortality are
      different. Both patients with PCD and patients with CF with pancreatic
      sufficiency (CF-PS) show no nutrient malabsorption and are diagnosed at a later
      age compared with patients with CF with pancreatic insufficiency (CF-PI).
      METHODS: Clinical status, microbiology, FEV1, and high-resolution CT (HRCT) scans
      presented as total Brody score (CT-TBS) were compared for patients with PCD, CF
      PI, and CF-PS, all treated at the same medical center, by the same team, and by a
      similar routine follow-up. RESULTS: One hundred sixty-four patients, 34 with PCD,
      88 with CF-PI, and 42 with CF-PS were enrolled. PCD was diagnosed at a similar
      age as CF-PS but significantly later than CF-PI. Mean FEV1 % predicted was
      similar for the three groups. The rate of FEV1 change with age in PCD was similar
      to CF-PS but significantly lower than in CF-PI. Severity of structural lung
      disease (CT-TBS) was similar for PCD and CF-PS and significantly higher in CF-PI.
      No correlation between TBS or Pseudomonas aeruginosa infection and FEV1 in PCD
      was seen, whereas a negative correlation with FEV1 was observed for both CF
      groups. CONCLUSIONS: Although in our study PCD was similar to CF-PS, the lack of
      correlation between FEV1 and age, CT-TBS, and P aeruginosa infection in PCD
      suggests that impaired mucociliary clearance is not the only cause for inducing
      pulmonary damage in these diseases. Furthermore, a comparison of disease
      characteristics for PCD and CF should distinguish between CF-PI and CF-PS as
      different entities.

PMID- 24091607
TI  - No washing, less waiting: engineering biomolecular reporters for single-step
      antibody detection in solution.
AB  - Detection of antibodies is essential for the diagnosis of many disease states,
      including infectious diseases, autoimmune diseases and allergies. Most current
      antibody detection assays involve multistep detection schemes in which molecular
      recognition and signal generation are separate processes. A well-known example is
      the enzyme-linked immunosorbent assay (ELISA), which combines high sensitivity
      and specificity with strong signal amplification. However, ELISA and other
      heterogeneous methods require multiple, time-consuming washing and incubation
      steps, which limits their applicability in point-of-care diagnostics and high
      throughput applications. In recent years, several new antibody detection
      strategies have been developed in which antibody binding and signal generation
      are integrated within a single biomolecular reporter. These strategies aim to
      rival ELISA in terms of sensitivity and specificity, while decreasing the time
      and effort required to perform an assay. Here, we review recent developments in
      this field according to their mechanism of action and discuss their advantages
      and limitations. 

PMID- 24091608
TI  - Towards successful Dissemination of Psychological First Aid: a study of provider
      training preferences.
AB  - Dissemination of Psychological First Aid (PFA) is challenging considering the
      complex nature of disaster response and the various disaster mental health (DMH)
      trainings available. To understand challenges to dissemination in community
      mental health centers (CMHCs), interviews were conducted with nine DMH providers
      associated with CMHCs. Consensual qualitative analysis was used to analyze data.
      Interviews were targeted toward understanding organizational infrastructure, DMH
      training requirements, and training needs. Results clarified challenges to DMH
      training in CMHCs and factors that may promote buy-in for trainings. For example,
      resources are limited and thus allocated for state and federal training
      requirements. Therefore, including PFA in these requirements could promote
      adoption. Additionally, a variety of training approaches that differ in content,
      style, and length would be useful. To conclude, a conceptual model for ways to
      promote buy-in for the PFA Guide is proposed. 

PMID- 24091609
TI  - Validity of Clinician's Self-Reported Practice Elements on the Monthly Treatment
      and Progress Summary.
AB  - An increased demand for accountability in community mental health systems has
      resulted in a need for valid, reliable measures of therapeutic practice. The
      Monthly Treatment and Progress Summary (MTPS), developed through the Hawaii Child
      and Adolescent Mental Health Division, is a clinician-report measure that
      describes therapeutic practices, treatment targets, and progress ratings for each
      treatment case. The current study evaluated the validity of the therapeutic
      strategies reported on the MTPS by comparing coder- and clinician-reported use of
      practices. Using 47 audio recordings from 19 youths' therapy sessions, trained
      observers reliably coded 12 discrete practices. Four of the 12 practices were
      found to be valid according to clinician-coder agreement (intraclass correlations
      >=0.60). The coding system was revised, utilizing extensiveness and experiential
      scales, and 100 % of practices were valid according to clinician-coder agreement.
      Practical use of the MTPS, implications for service systems, and future
      directions for research on the MTPS are discussed.

PMID- 24091610
TI  - Implementation of consumer providers into mental health intensive case management
      teams.
AB  - In mental health care, consumer providers (CPs) are individuals with serious
      mental illness (SMI) who draw upon their lived experiences while providing
      services to others with SMI. Implementation of CPs has proven to be challenging
      in a variety of settings. The PEER project (Peers Enhancing Recovery) involved
      rolling out CPs using an implementation science model and evaluating
      implementation and impact in mental health treatment settings (three
      intervention, three control). In qualitative interviews, facilitators and
      challenges to implementation were described by the CPs, their team members,
      clients, and study researchers. Site preparation, external facilitation, and
      positive, reinforcing experiences with CPs facilitated implementation. Role
      definitions and deficiencies in CPs' technical knowledge posed challenges to
      implementation. Sustainability was not realized due to insufficient resources.
      However, implementation was positive overall, characterized by diffusion of
      innovation concepts of high relative advantage, strong trialability,
      compatibility with prevailing norms, compelling observability, and relatively low
      complexity. By preparing and working systematically with intervention sites to
      incorporate new services, implementation was strengthened and challenges were
      minimized. 

PMID- 24091611
TI  - Evaluation of a randomized intervention to increase adoption of comparative
      effectiveness research by community health organizations.
AB  - This randomized controlled trial examined the influence of two strategies
      (informational packets alone and in conjunction with Webinars) aimed at
      increasing the adoption of motivational interviewing (MI), a patient-centered
      behavioral health practice supported by evidence from comparative effectiveness
      studies, among community health organizations responsible for delivering mental
      and behavioral health services. Data were obtained from 311 directors and staff
      across 92 community organizations. Hierarchical linear modeling was used to
      examine changes in decision to adopt MI. The mediating effects of multiple
      contextual variables were also examined. Results showed that both strategies
      positively influenced the decision to adopt. The positive impact on decision to
      adopt was significantly greater among individuals that received informational
      packets in conjunction with Webinars. Baseline attitudes toward evidence-based
      practices and pressures for change appeared to mediate this effect.

PMID- 24091612
TI  - A Preliminary Study Examining Nutritional Risk Factors, Body Mass Index, and
      Treatment Retention in Opioid-Dependent Patients.
AB  - Poor nutritional health among opioid-dependent individuals is well established,
      yet no nutritional screening tool exists for this specific population. The
      utility of "Determine Your Nutritional Health" developed by the Nutrition
      Screening Initiative is considered. The study examines the questionnaire's
      relevance in patients beginning opioid dependence treatment at a methadone
      assisted treatment program (N = 140) by examining nutritional risk factor
      prevalence, body mass index, and association between nutritional risk level and
      treatment retention. The majority of patients reported at least one nutritional
      risk factor (89 %) and 59 % were at high nutritional risk. Body mass index was
      not related to nutritional risk; however, a trend was identified between
      increasing nutritional risk and decreased retention in treatment. These
      preliminary findings suggest the need for incorporation of nutritional screening
      at intake in opioid treatment programs, consideration of the effect of dietary
      risk on treatment retention, and the potential utility of this screening tool.

PMID- 24091613
TI  - The impact of regional reconfiguration on the management of appendicitis.
AB  - BACKGROUND: Reconfiguration of surgical services in the Mid-West in 2009 resulted
      in a large increase in numbers of patients undergoing emergency surgery for
      appendicitis in University Hospital Limerick (UHL). AIMS: The aim of this study
      was to assess the impact of reconfiguration on the management of appendicitis in
      this area. METHODS: Data on all patients who underwent appendicectomy between
      January and June 2007 were compared with the corresponding data from January to
      June 2011. The numbers of operations, types of operations, lengths of stay (LOS),
      operation start times, rates of negative histology specimens and readmissions
      within 30 days were compared. One hundred and twenty-five appendicectomies [48
      laparoscopic (38.4 %)] were performed in the 2007 group of which 32 specimens
      (25.6 %) were histologically negative. Three hundred and nineteen
      appendicectomies [238 laparoscopic (74.6 %)] were performed in the 2011 group of
      which 62 specimens (19.4 %) were histologically negative. The increase in numbers
      of laparoscopic procedures was significant (p < 0.001). The reduction in the
      negative appendicectomy rate was not statistically significant (p = 0.16). There
      were 10 conversions (20.8 %) to open surgery in the 2007 period and 12 (5 %) in
      the 2011 period (p = 0.001). Mean LOS for the 2007 and 2011 groups was 4.45 and
      3.16 days (p < 0.001). Six (4.8 %) readmissions within 30 days occurred in the
      2007 group with 20 (6.3 %) in the 2011 group (p = 0.66). CONCLUSION: Though
      reconfiguration of surgical services has resulted in a significant increase in
      workload, LOS has decreased significantly while maintaining acceptably low
      negative appendicectomy, conversion and readmission rates.

PMID- 24091614
TI  - Melanoma in primary care. The role of the general practitioner.
AB  - BACKGROUND: The British Association of Dermatologists and the National Cancer
      Control Programme in Ireland discourage all GPs from biopsying any lesions
      suspicious of melanoma. AIM: The aim of this study was to assess whether or not
      it is safe and practical for a general practitioner with extra training in
      dermatology and skin surgery to assess suspicious skin lesions and treat low risk
      melanomas. METHOD: The outcome of 56 new melanomas (31 invasive, 7 in situ and 18
      lentigo maligna) in 53 patients, managed by a GP with extra training in
      dermatology and skin surgery, over a 20 year period, was examined. RESULTS: Forty
      eight (86 %) of the melanomas had the initial biopsy carried out in primary care.
      The average time from presentation to the practice to the date of the biopsy was
      8 days for the in situ and invasive melanomas and 17 days for the lentigo
      malignas. Twenty-eight (50 %) of the melanomas were considered low risk (in situ,
      invasive <1 mm deep or lentigo maligna) and were treated successfully in primary
      care according to the Australian and New Zealand guidelines, without any surgical
      complications. CONCLUSION: GPs with extra training in skin cancer and skin
      surgery could assess most suspicious skin lesions with dermoscopy and if
      necessary, biopsy most of these lesions in primary care. This would lead to a
      quicker diagnosis, more rapid pathway to definitive treatment, lower cost and
      more convenience to the patient, especially for those living in rural areas.

PMID- 24091616
TI  - Review: depression after myocardial infarction is associated with increased risk
      of all-cause mortality and cardiovascular events.

PMID- 24091617
TI  - Current use of second-generation antipsychotics may increase risk of pneumonia in
      people with schizophrenia.

PMID- 24091615
TI  - Timeliness of care and prognosis in patients with lung cancer.
AB  - BACKGROUND: Timeliness of care is an important dimension of health care quality.
      The determining factors of less timely care and their influence on the survival
      of patients with lung cancer (LC) remain uncertain. AIMS: To analyse the delays
      in the diagnosis and treatment of LC in our health area, the factors associated
      with the timeliness of care and their possible relationship with the survival of
      these patients. METHODS: A retrospective study was conducted on all patients with
      a cytohistologically confirmed diagnosis of LC between 1 June 2005 and 31 May
      2008. The time delays for consultation (specialist delay), diagnosis (diagnosis
      delay), and treatment (treatment delay), were analysed, as well as the factors
      associated with these delays and the influence of the timeliness of care on
      survival. RESULTS: A total of 307 cases were included (87 % males). The mean
      specialist delay was 53.6 days (median 35 days), diagnosis delay 31.5 days
      (median 18 days), treatment delay 23.5 days (median 14 days). The greater age of
      the patient and a more advanced stage were associated with a shorter specialist
      delay. Male sex, a more advanced stage, and poor general status were associated
      with a shorter treatment delay. The survival is longer in patients with a longer
      treatment delay. CONCLUSIONS: The delay in the diagnosis in our population seems
      to be excessively long. The greater the age, a more advanced tumour stage, male
      sex, and poor general health status are associated with shorter delays. A longer
      treatment delay is associated with a longer survival.

PMID- 24091618
TI  - Review: different psychotherapies have comparable effects on adult depression.

PMID- 24091619
TI  - Acquired resistance to temsirolimus in human renal cell carcinoma cells is
      mediated by the constitutive activation of signal transduction pathways through
      mTORC2.
AB  - BACKGROUND: The objective of this study was to characterise the mechanism
      underlying acquired resistance to temsirolimus, an inhibitor of mammalian target
      of rapamycin (mTOR), in renal cell carcinoma (RCC). METHODS: A parental human RCC
      cell line, ACHN (ACHN/P), was continuously exposed to increasing doses of up to
      20 MUM of temsirolimus, and a cell line resistant to temsirolimus (ACHN/R),
      showing a sixfold higher IC50 than that of ACHN/P, was developed. RESULTS:
      Following treatment with temsirolimus, phosphorylation of S6 kinase in ACHN/P was
      markedly inhibited, whereas there was no detectable expression of phosphorylated
      S6 in ACHN/R before and after temsirolimus treatment. However, AKT and p44/42
      mitogen-activated protein kinase (MAPK) were constitutively phosphorylated even
      after temsirolimus treatment in ACHN/R, but not in ACHN/P. There was no
      significant difference between the sensitivities of ACHN/P and ACHN/R to
      KU0063794, a dual inhibitor of mTOR complex 1 (mTORC1) and mTORC2. Similar
      sensitivities to temsirolimus in ACHN/P and ACHN/R could be achieved by
      additional treatment with specific inhibitors of AKT- and MAPK-signaling
      pathways. CONCLUSION: The activation of signal transduction pathways via mTORC2,
      but not via mTORC1, may have an important role in the acquisition of a resistant
      phenotype to temsirolimus in RCC.

PMID- 24091620
TI  - Quality of life during chemotherapy in lung cancer patients: results across
      different treatment lines.
AB  - BACKGROUND: Most lung cancer patients are diagnosed at an advanced disease stage
      and predominantly receive palliative treatment, which increasingly consists of
      several chemotherapy lines. We report on patients' quality of life (QOL) to gain
      knowledge on QOL during and across multiple lines of chemotherapy. This includes
      patients with (neo)adjuvant therapy up to 3rd or above line palliative
      chemotherapy. METHODS: Lung cancer patients receiving outpatient chemotherapy at
      the Kufstein County Hospital completed an electronic version of the EORTC QLQ
      C30. Linear mixed models were used for statistical analysis. RESULTS: One hundred
      and eighty seven patients were included in the study. Surprisingly, irrespective
      of the chemotherapy line patients reported stable QOL scores during treatment.
      None of the calculated monthly change rates attained clinical significance,
      referring to established guidelines that classify a small clinical meaningful
      change as 5 to 10 points. According to treatment line, 3rd or above line
      palliative chemotherapy was associated with the worst QOL scores, whereas
      patients undergoing (neo)adjuvant or 1st line palliative chemotherapy reported
      fairly comparable QOL. CONCLUSION: The essential finding of our study is that all
      QOL aspects of the EORTC QLQ-C30 questionnaire remained unchanged during each
      chemotherapy line in an unselected population of lung cancer patients. Between
      treatment lines pronounced differences were found, indicating that later
      palliative chemotherapy lines are associated with higher QOL impairments. These
      changes in QOL may not primarily be related to the treatment, but rather refer to
      impairments due to disease progression and may be partly due to a consequence of
      the prior therapies.

PMID- 24091621
TI  - p53 and cell cycle independent dysregulation of autophagy in chronic lymphocytic
      leukaemia.
AB  - BACKGROUND: Activation of wild-type p53 with the small molecule sirtuin inhibitor
      Tenovin-6 (Tnv-6) induces p53-dependent apoptosis in many malignant cells. In
      contrast, Tnv-6 reduces chronic lymphocytic leukaemia (CLL) cell viability with
      dysregulation of autophagy, without increasing p53-pathway activity. METHODS:
      Here, we have investigated whether a quiescent phenotype (unique to CLL)
      determines the Tnv-6 response, by comparing the effects of Tnv-6 on activated and
      proliferating CLL. We further studied if these responses are p53-dependent.
      RESULTS: Unlike quiescent cells, cell death in activated cultures treated with
      Tnv-6 was consistently associated with p53 upregulation. However, p53 acetylation
      remained unchanged, without caspase-3 cleavage or apoptosis on electron
      microscopy. Instead, cellular ultrastructure and protein profiles indicated
      autophagy inhibition, with reduced ubiquitin-proteasome activity. In specimens
      with mutant TP53 cultured with Tnv-6, changes in the autophagy-associated protein
      LC3 occurred independently of p53. Cells treated with Tnv-6 analogues lacking
      sirtuin inhibitory activity had attenuated LC3 lipidation compared with Tnv-6
      (P?0.01), suggesting that autophagy dysregulation occurs predominantly through an
      effect on sirtuins. CONCLUSION: These cell cycle and p53-independent anti
      leukaemic mechanisms potentially offer novel therapeutic approaches to target
      leukaemia-sustaining cells in CLL, including in disease with p53-pathway
      dysfunction. Whether targets in addition to sirtuins contribute to autophagy
      dysregulation by Tnv-6, requires further investigation.

PMID- 24091622
TI  - Tumour-suppressive microRNA-29s inhibit cancer cell migration and invasion by
      targeting laminin-integrin signalling in head and neck squamous cell carcinoma.
AB  - BACKGROUND: Our recent studies of microRNA (miRNA) expression signatures
      demonstrated that microRNA-29s (miR-29s; miR-29a/b/c) were significantly
      downregulated in head and neck squamous cell carcinoma (HNSCC) and were putative
      tumour-suppressive miRNAs in human cancers. Our aim in this study was to
      investigate the functional significance of miR-29s in cancer cells and to
      identify novel miR-29s-mediated cancer pathways and responsible genes in HNSCC
      oncogenesis and metastasis. METHODS: Gain-of-function studies using mature miR
      29s were performed to investigate cell proliferation, migration and invasion in
      two HNSCC cell lines (SAS and FaDu). To identify miR-29s-mediated molecular
      pathways and targets, we utilised gene expression analysis and in silico database
      analysis. Loss-of-function assays were performed to investigate the functional
      significance of miR-29s target genes. RESULTS: Restoration of miR-29s in SAS and
      FaDu cell lines revealed significant inhibition of cancer cell migration and
      invasion. Gene expression data and in silico analysis demonstrated that miR-29s
      modulated the focal adhesion pathway. Moreover, laminin gamma2 (LAMC2) and alpha6
      integrin (ITGA6) genes were candidate targets of the regulation of miR-29s.
      Luciferase reporter assays showed that miR-29s directly regulated LAMC2 and
      ITGA6. Silencing of LAMC2 and ITGA6 genes significantly inhibited cell migration
      and invasion in cancer cells. CONCLUSION: Downregulation of miR-29s was a
      frequent event in HNSCC. The miR-29s acted as tumour suppressors and directly
      targeted laminin-integrin signalling. Recognition of tumour-suppressive miRNA
      mediated cancer pathways provides new insights into the potential mechanisms of
      HNSCC oncogenesis and metastasis and suggests novel therapeutic strategies for
      the disease.

PMID- 24091624
TI  - Mesoscopic fluorescence molecular tomography of reporter genes in bioprinted
      thick tissue.
AB  - Three-dimensional imaging of thick tissue constructs is one of the main
      challenges in the field of tissue engineering and regenerative medicine. Optical
      methods are the most promising as they offer noninvasive, fast, and inexpensive
      solutions. Herein, we report the use of mesoscopic fluorescence molecular
      tomography (MFMT) to image function and structure of thick bioprinted tissue
      hosted in a 3-mm-thick bioreactor. Collagen-based tissue assembled in this study
      contains two vascular channels formed by green fluorescent protein- and mCherry
      expressing cells. Transfected live cell imaging enables us to image function,
      whereas Flash Red fluorescent bead perfusion into the vascular channel allows us
      to image structure. The MFMT optical reconstructions are benchmarked with
      classical microscopy techniques. MFMT and wide-field fluorescence microscopy data
      match within 92% in area and 84% in location, validating the accuracy of MFMT
      reconstructions. Our results demonstrate that MFMT is a well-suited imaging
      modality for fast, longitudinal, functional imaging of thick, and turbid tissue
      engineering constructs.

PMID- 24091623
TI  - Do type 1 receptor tyrosine kinases inform treatment choice? A prospectively
      planned analysis of the TEAM trial.
AB  - BACKGROUND: Epidermal growth factor receptors contribute to breast cancer relapse
      during endocrine therapy. Substitution of aromatase inhibitors (AIs) may improve
      outcomes in HER-positive cancers. METHODS: Tissue microarrays were constructed.
      Quantitative analysis of HER1, HER2, and HER3 was performed. Data were analysed
      relative to disease-free survival and treatment using outcomes at 2.75 and 6.5
      years. RESULTS: Among 4541 eligible samples, 4225 (93%) had complete HER1-3 data.
      Overall, 5% were HER1-positive, 13% HER2-positive, and 21% HER3-positive; 32%
      (n=1351) overexpressed at least one HER receptor. In the HER1-3-negative
      subgroup, the hazard ratio (HR) for upfront exemestane vs tamoxifen at 2.75 years
      was 0.67 (95% confidence interval (CI), 0.52-0.87), in the HER1-3-positive
      subgroup, the HR was 1.15 (95% CI, 0.85-1.56). A prospectively planned treatment
      by-marker analysis demonstrated a significant interaction between HER1-3 and
      treatment at 2.75 years (HR=0.58; 95% CI, 0.39-0.87; P=0.008), as confirmed by
      multivariate regression analysis adjusting for prognostic factors (HR=0.55; 95%
      CI, 0.36-0.85; P=0.005). This effect was time dependent. CONCLUSION: In the 2.75
      years prior to switching patients initially treated with tamoxifen to exemestane,
      a significant treatment-by-marker effect exists between AI/tamoxifen treatment
      and HER1-3 expression, suggesting HER expression could be used to select
      appropriate endocrine treatment at diagnosis to prevent or delay early relapses.

PMID- 24091625
TI  - Study on reflection of human skin with liquid paraffin as the penetration
      enhancer by spectroscopy.
AB  - Optical clearing agents can improve tissue optical transmittance by reducing the
      diffuse reflection. The reflection on in vivo human skin before and after
      applying anhydrous glycerol and 30 to 50% liquid paraffin glycerol mixed solution
      are investigated in this paper. From their visible and near-infrared reflection
      spectroscopy, all of their diffuse reflections are reduced after applying the
      agents. It is found that the three mixed solutions show stronger effect than that
      of anhydrous glycerol. These results further prove liquid paraffin can enhance
      the percutaneous penetration of glycerol and take synergistically optical
      clearing effect with glycerol over visible and near-infrared wave bands.

PMID- 24091626
TI  - Nature vs nurture: interplay between the genetic control of telomere length and
      environmental factors.
AB  - Telomeres are nucleoprotein structures that cap the ends of the linear eukaryotic
      chromosomes, thus protecting their stability and integrity. They play important
      roles in DNA replication and repair and are central to our understanding of aging
      and cancer development. In rapidly dividing cells, telomere length is maintained
      by the activity of telomerase. About 400 TLM (telomere length maintenance) genes
      have been identified in yeast, as participants of an intricate homeostasis
      network that keeps telomere length constant. Two papers have recently shown that
      despite this extremely complex control, telomere length can be manipulated by
      external stimuli. These results have profound implications for our understanding
      of cellular homeostatic systems in general and of telomere length maintenance in
      particular. In addition, they point to the possibility of developing aging and
      cancer therapies based on telomere length manipulation. 

PMID- 24091627
TI  - microRNA-141 regulates BMI1 expression and induces senescence in human diploid
      fibroblasts.
AB  - Polycomb group protein BMI1 is an important regulator of senescence, aging, and
      cancer. On one hand, it is overexpressed in cancer cells and is required for self
      renewal of stem cells. On the other hand, it is downregulated during senescence
      and aging. MicroRNAs have emerged as major regulators of almost every gene
      associated with cancer, aging, and related pathologies. At present, very little
      is known about the miRNAs that regulate the expression of BMI1. Here, we report
      that miR-141 posttranscriptionally downregulates BMI1 expression in human diploid
      fibroblasts (HDFs) via a miR-141 targeting sequence in the 3' untranslated region
      of BMI1 mRNA. We also show that overexpression of miR-141 induces premature
      senescence in HDFs via targeting of BMI1 in normal but not in exogenous BMI1
      overexpressing HDFs. Induction of premature senescence in HDFs was accompanied by
      upregulation of p16INK4a, an important downstream target of BMI1 and a major
      regulator of senescence. Our results suggest that miR-141-based therapies could
      be developed to treat pathologies where BMI1 is deregulated. 

PMID- 24091628
TI  - Differential regulation of FBXW7 isoforms by various stress stimuli.
AB  - Fbxw7 is a tumor suppressor mutated in a wide range of human cancers. It serves
      as the substrate recognition component of SCF E3 ubiquitin ligases, and intensive
      effort was made to identify its substrates. Some of the substrates are central
      regulators of the cell cycle, cell fate determination, and cellular survival.
      Unlike the many efforts aimed at identifying novel targets, little is known about
      the regulation of Fbw7 isoform expression. In this study, we examined the mRNA
      expression of different FBXW7 isoforms during the cell cycle and after exposure
      to various stress stimuli. We observed that Fbw7beta is induced by all the stress
      stimuli tested, mostly, but not exclusively, in a p53-dependent manner. In fact,
      FBXW7beta was found to be the most potently induced p53 target gene in HCT-116
      cells. Expression of FBXWalpha and gamma is p53-independent and their
      responsiveness to most stress stimuli is limited. Furthermore, their pattern of
      stress responsiveness is very different from that of the beta isoform. Under
      certain conditions, the same genotoxic agent stimulates induction of beta and
      repression of alpha. Analysis of FACS-sorted cells in specific phases of the cell
      cycle by using fluorescent ubiquitination-based cell cycle indicator (FUCCI),
      showed a significant repression of the gamma isoform during the S phase of normal
      cycling HCT-116 cells. Altogether, this study suggests differential regulation of
      the 3 Fbw7 isoforms. 

PMID- 24091629
TI  - Is activation of the intra-S checkpoint in human fibroblasts an important factor
      in protection against UV-induced mutagenesis?
AB  - The ATR/CHK1-dependent intra-S checkpoint inhibits replicon initiation and
      replication fork progression in response to DNA damage caused by UV (UV)
      radiation. It has been proposed that this signaling cascade protects against UV
      induced mutations by reducing the probability that damaged DNA will be replicated
      before it can be repaired. Normal human fibroblasts (NHF) were depleted of ATR or
      CHK1, or treated with the CHK1 kinase inhibitor TCS2312, and the UV-induced
      mutation frequency at the HPRT locus was measured. Despite clear evidence of S
      phase checkpoint abrogation, neither ATR/CHK1 depletion nor CHK1 inhibition
      caused an increase in the UV-induced HPRT mutation frequency. These results
      question the premise that the UV-induced intra-S checkpoint plays a prominent
      role in protecting against UV-induced mutagenesis. 

PMID- 24091630
TI  - Large oncosomes mediate intercellular transfer of functional microRNA.
AB  - Prostate cancer cells release atypically large extracellular vesicles (EVs),
      termed large oncosomes, which may play a role in the tumor microenvironment by
      transporting bioactive molecules across tissue spaces and through the blood
      stream. In this study, we applied a novel method for selective isolation of large
      oncosomes applicable to human platelet-poor plasma, where the presence of
      caveolin-1-positive large oncosomes identified patients with metastatic disease.
      This procedure was also used to validate results of a miRNA array performed on
      heterogeneous populations of EVs isolated from tumorigenic RWPE-2 prostate cells
      and from isogenic non-tumorigenic RWPE-1 cells. The results showed that distinct
      classes of miRNAs are expressed at higher levels in EVs derived from the
      tumorigenic cells in comparison to their non-tumorigenic counterpart. Large
      oncosomes enhanced migration of cancer-associated fibroblasts (CAFs), an effect
      that was increased by miR-1227, a miRNA abundant in large oncosomes produced by
      RWPE-2 cells. Our findings suggest that large oncosomes in the circulation report
      metastatic disease in patients with prostate cancer, and that this class of EV
      harbors functional molecules that may play a role in conditioning the tumor
      microenvironment. 

PMID- 24091631
TI  - Cyclin-dependent kinase 4 may be expressed as multiple proteins and have
      functions that are independent of binding to CCND and RB and occur at the S and G
      2/M phases of the cell cycle.
AB  - Cyclin-dependent kinase 4 (CDK4) is known to be a 33 kD protein that drives G 1
      phase progression of the cell cycle by binding to a CCND protein to phosphorylate
      RB proteins. Using different CDK4 antibodies in western blot, we detected 2
      groups of proteins around 40 and 33 kD, respectively, in human and mouse cells;
      each group often appeared as a duplet or triplet of bands. Some CDK4 shRNAs could
      decrease the 33 kD wild-type (wt) CDK4 but increase some 40 kD proteins, whereas
      some other shRNAs had the opposite effects. Liquid chromatography-mass
      spectrometry/mass spectrometry analysis confirmed the existence of CDK4 isoforms
      smaller than 33 kD but failed to identify CDK4 at 40 kD. We cloned one CDK4 mRNA
      variant that lacks exon 2 and encodes a 26 kD protein without the first 74 amino
      acids of the wt CDK4, thus lacking the ATP binding sequence and the PISTVRE
      domain required for binding to CCND. Co-IP assay confirmed that this DeltaE2
      protein lost CCND1- and RB1-binding ability. Moreover, we found, surprisingly,
      that the wt CDK4 and the DeltaE2 could inhibit G 1-S progression, accelerate S-G
      2/M progression, and enhance or delay apoptosis in a cell line-specific manner in
      a situation where the cells were treated with a CDK4 inhibitor or the cells were
      serum-starved and then replenished. Hence, CDK4 seems to be expressed as multiple
      proteins that react differently to different CDK4 antibodies, respond differently
      to different shRNAs, and, in some situations, have previously unrecognized
      functions at the S-G 2/M phases of the cell cycle via mechanisms independent of
      binding to CCND and RB. 

PMID- 24091634
TI  - How much nicotine kills a human? Tracing back the generally accepted lethal dose
      to dubious self-experiments in the nineteenth century.

PMID- 24091633
TI  - microRNA-34a promotes DNA damage and mitotic catastrophe.
AB  - Efficient and error-free DNA repair is critical for safeguarding genome
      integrity, yet it is also linked to radio- and chemoresistance of malignant
      tumors. miR-34a, a potent tumor suppressor, influences a large set of p53
      regulated genes and contributes to p53-mediated apoptosis. However, the effects
      of miR-34a on the processes of DNA damage and repair are not entirely understood.
      We explored tet-inducible miR-34a-expressing human p53 wild-type and R273H p53
      mutant GBM cell lines, and found that miR-34a influences the broad spectrum of
      53BP1-mediated DNA damage response. It escalates both post-irradiation and
      endogenous DNA damage, abrogates radiation-induced G 2/M arrest and drastically
      increases the number of irradiated cells undergoing mitotic catastrophe.
      Furthermore, miR-34a downregulates 53BP1 and inhibits its recruitment to the
      sites of DNA double-strand breaks. We conclude that whereas miR-34a counteracts
      DNA repair, it also contributes to the p53-independent elimination of distressed
      cells, thus preventing the rise of genomic instability in tumor cell populations.
      These properties of miR-34a can potentially be exploited for DNA damage-effecting
      therapies of malignancies. 

PMID- 24091635
TI  - Response to Morfeld (2013): Second commentary to Gebel 2012-established use of
      cancer potency indices and biological plausibility.
AB  - The evaluations in Gebel (Arch Toxicol 86(7):995-1007, 2012) were carried out
      according to established procedures in regulatory toxicology. The variability in
      the available data was taken into account. The quality of the underlying data set
      should not be overestimated. The relevant conclusion in Gebel (Arch Toxicol
      86(7):995-1007, 2012) is that the difference in carcinogenic potency comparing
      nanosized to microsized respirable granular biodurable particles without known
      significant specific toxicity (GBP) is low and lower than previously estimated. 

PMID- 24091636
TI  - Methylarsonous acid causes oxidative DNA damage in cells independent of the
      ability to biomethylate inorganic arsenic.
AB  - Inorganic arsenic (iAs) and its toxic methylated metabolite, methylarsonous acid
      (MMA(III)), both have carcinogenic potential. Prior study shows iAs-induced
      malignant transformation in both arsenic methylation-proficient (liver) and
      methylation-deficient (prostate) cells, but only methylation-proficient cells
      show oxidative DNA damage (ODD) during this transformation. To further define
      whether arsenic methylation is necessary for transformation or ODD induction,
      here we chronically exposed these same liver or prostate cell lines to MMA(III)
      (0.25-1.0 MUM) and tested for acquired malignant phenotype. Various metrics of
      oncogenic transformation were periodically assessed along with ODD during chronic
      MMA(III) exposure. Methylation-deficient and methylation-proficient cells both
      acquired a cancer phenotype with MMA(III) exposure at about 20 weeks, based on
      increased matrix metalloproteinase secretion, colony formation, and invasion. In
      contrast, prior work showed iAs-induced transformation took longer in
      biomethylation-deficient cells (~30 weeks) than in biomethylation-proficient
      cells (~18 weeks). In the present study, MMA(III) caused similar peak ODD levels
      at similar concentrations and at similar exposure times (18-22 weeks) in both
      cell types. At the approximate peak of ODD production, both cell types showed
      similar alterations in arsenic and oxidative stress adaptation factors (i.e.,
      ABCC1, ABCC2, GST-pi, SOD-1). Thus, MMA(III) causes oncogenic transformation
      associated with ODD in methylation-deficient cells, indicating that further
      methylation is not required to induce ODD. Together, these results show that
      MMA(III) and iAs cause an acquired malignant phenotype in methylation-deficient
      cells, yet iAs does not induce ODD. This indicates iAs likely has both genotoxic
      and non-genotoxic mechanisms dictated by the target cell's ability to methylate
      arsenic.

PMID- 24091638
TI  - A straight left heart border: a new radiological sign of a hemopericardium.
AB  - BACKGROUND: Detection of a cardiac injury in a stable patient after a penetrating
      chest injury can be difficult. Ultrasound of the pericardial sac may be
      associated with a false negative result in the presence of a hemothorax. A
      filling in of the left heart border inferior to the pulmonary artery, called the
      straight left heart border (SLHB), is a radiological sign on chest X-ray that we
      have found to be associated with the finding of a hemopericardium at surgery. The
      aim of the present study was to determine if this was a reliable and reproducible
      sign. METHODS: This was a prospective study of patients with a penetrating chest
      injury admitted between 1 October 2001 and 28 February 2009, who had no
      indication for immediate surgery, and were taken to the operating room for
      creation of a subxiphoid pericardial window (SPW). The chest X-ray was reviewed
      by a single trauma surgeon prior to surgery. RESULTS: A total of 162 patients
      with a possible occult cardiac injury underwent creation of a SPW. Fifty-five of
      the 162 patients (34 %) were noted to have a SLHB on chest X-ray and a
      hemopericardium confirmed at SPW. The sensitivity of the SLHB sign was 40 %;
      specificity, 84 %; and positive predictive value, 89 %. (p = 0.005, Odds ratio
      3.48, lower 1.41, upper 8.62). CONCLUSIONS: The straight left heart border is a
      newly described radiological sign that was highly significant in predicting the
      presence of a hemopericardium and should alert the clinician to a possible occult
      cardiac injury.

PMID- 24091637
TI  - Quality gaps and comparative effectiveness in lung cancer staging and diagnosis.
AB  - BACKGROUND: Guidelines recommend mediastinal lymph node sampling as the first
      invasive test in patients with suspected lung cancer with mediastinal
      lymphadenopathy without distant metastases, but there are no comparative
      effectiveness studies on how test sequencing affects outcomes. The objective was
      to compare practice patterns and outcomes of diagnostic strategies in patients
      with lung cancer. METHODS: The study included a retrospective cohort of 15,316
      patients with lung cancer with regional spread without distant metastases in the
      Surveillance, Epidemiology, and End Results or Texas Cancer Registry Medicare
      linked databases. If the first invasive test involved mediastinal sampling,
      patients were classified as receiving guideline-consistent care; otherwise, they
      were classified as receiving guideline-inconsistent care. We used propensity
      matching to compare the number of tests performed and multivariate logistic
      regression to compare the frequency of complications. RESULTS: Twenty-one percent
      of patients had guideline-consistent diagnostic evaluations. Among patients with
      non-small cell lung cancer, 44% never had mediastinal sampling. Patients who had
      guideline-consistent care required fewer tests than those with guideline
      inconsistent care (P < .0001), including thoracotomies (49% vs 80%, P < .001) and
      CT image-guided biopsies (9% vs 63%, P < .001), although they had more
      transbronchial needle aspirations (37% vs 4%, P < .001). The consequence was that
      patients with guideline-consistent care had fewer pneumothoraxes (4.8% vs 25.6%,
      P < .0001), chest tubes (0.7% vs 4.9%, P < .001), hemorrhages (5.4% vs 10.6%, P <
      .001), and respiratory failure events (5.3% vs 10.5%, P < .001). CONCLUSIONS:
      Guideline-consistent care with mediastinal sampling first resulted in fewer tests
      and complications. We found three quality gaps: failure to sample the mediastinum
      first, failure to sample the mediastinum at all in patients with non-small cell
      lung cancer, and overuse of thoracotomy.

PMID- 24091639
TI  - Cascade fluorofunctionalisation of 2,3-unsubstituted indoles by means of
      electrophilic fluorination.
AB  - Cascade fluorofunctionalisation of 2,3-unsubstituted indoles featuring the
      formation of C-C, C-F and C-O bonds via electrophilic fluorination using N
      fluorobenzenesulfonimide is described. The use of an O-nucleophile tethered to
      the nitrogen of indoles enables the synthesis of polycyclic fluorinated indoline
      derivatives from simple precursors in 40-63% yields. 

PMID- 24091641
TI  - Palladium(II)-(E,N,E) pincer ligand (E = S/Se/Te) complex catalyzed Suzuki
      coupling reactions in water via in situ generated palladium quantum dots.
AB  - The (E,N,E) pincer ligands (ArECH2CH2)2NH (L1/L2: Ar = Ph, E = S/Se; L3: Ar =
      CH3O-p-C6H4, E = Te) synthesized by reaction of PhS(-)/PhSe(-)/CH3O-p-C6H4Te(-)
      with bis(2-chloroethyl)amine react with Na2PdCl4 in aqueous ethanol, resulting in
      nearly square planar diamagnetic complexes [Pd(L)Cl]Cl (1-3), where L = L1-L3.
      All the ligands (L1-L3) and their complexes (1-3) have been characterised with
      (1)H, (13)C{(1)H}, (77)Se{(1)H} and (125)Te{(1)H} NMR spectra and high resolution
      mass spectrometry. The single crystal structures (determined with X-ray
      diffraction) of 2 and 3 have been solved (Pd-Se: 2.4104(5)/2.4222(6) A; Pd-Te:
      2.560(2)/2.588(2) A). The conversions for Suzuki-Miyaura coupling (SMC) of
      various aryl bromides with phenylboronic and 4-formyl/acetyl phenylboronic acid
      in water using 2-3 mol% of each of the complexes 1-3 have been found good.
      Complexes 1 and 2 show better catalytic activity than 3, as higher yields were
      observed with them in a relatively short time. The coupling reactions appear to
      be catalyzed with Pd(0) nanoparticles (NPs) generated in situ in the course of
      reaction. The NPs have been isolated and HRTEM studies on them have revealed
      their size as ~1-3 nm. The SEM-EDX indicates their protection with
      organochalcogen fragments. Addition of TBAB was essential in some cases to get
      good yield of cross coupled product. The isolated NPs show catalytic activity for
      SMC independently. The yields of cross coupled product were excellent when NPs
      were reused. The two phase test suggests a relatively low contribution of
      homogeneous Pd species in catalysis. 

PMID- 24091640
TI  - Microbead-based biomimetic synthetic neighbors enhance survival and function of
      rat pancreatic beta-cells.
AB  - Diabetes is caused by the loss or dysfunction of insulin-secreting beta-cells in
      the pancreas. beta-cells reduce their mass and lose insulin-producing ability in
      vitro, likely due to insufficient cell-cell and cell-extracellular matrix (ECM)
      interactions as beta-cells lose their native microenvironment. Herein, we built
      an ex-vivo cell microenvironment by culturing primary beta-cells in direct
      contact with 'synthetic neighbors', cell-sized soft polymer microbeads that were
      modified with cell-cell signaling factors as well as components from pancreatic
      tissue-specific ECMs. This biomimetic 3D microenvironment was able to promote
      native cell-cell and cell-ECM interactions. We obtained sustained maintenance of
      beta-cell function in vitro enhanced cell viability from the few days usually
      observed in 2D culture to periods exceeding three weeks, with enhanced beta-cell
      stability and insulin production. Our approach can be extended to create a
      general 3D culture platform for other cell types. 

PMID- 24091642
TI  - Reversal of facial selectivity in a thia-Claisen rearrangement by incorporation
      of a vinylic bromine substituent.
AB  - Thia-Claisen rearrangements have been carried out using N-benzylpyrrolidine-2
      thione and chiral allylic bromides derived from D-mannitol. Introduction of a
      bromine atom onto the double bond of the allylic bromide reverses the sense of
      diastereoselectivity in the [3,3]-sigmatropic rearrangement. Density functional
      theory calculations lead us to rationalise the observed selectivity in terms of a
      Cieplak effect.

PMID- 24091643
TI  - A statistical approach to distinguish telomere elongation from error in
      longitudinal datasets.
AB  - Telomere length and the rate of telomere attrition vary between individuals and
      have been interpreted as the rate at which individuals have aged. The biology of
      telomeres dictates shortening with age, although telomere elongation with age has
      repeatedly been observed within a minority of individuals in several populations.
      These findings have been attributed to error, rather than actual telomere
      elongation, restricting our understanding of its possible biological
      significance. Here we present a method to distinguish between error and telomere
      elongation in longitudinal datasets, which is easy to apply and has few
      assumptions. Using simulations, we show that the method has considerable
      statistical power (>80 %) to detect even a small proportion (6.7 %) of TL
      increases in the population, within a relatively small sample (N = 200), while
      maintaining the standard level of Type I error rate (alpha <= 0.05). 

PMID- 24091644
TI  - How well do mean field theories of spiking quadratic-integrate-and-fire networks
      work in realistic parameter regimes?
AB  - We use mean field techniques to compute the distribution of excitatory and
      inhibitory firing rates in large networks of randomly connected spiking quadratic
      integrate and fire neurons. These techniques are based on the assumption that
      activity is asynchronous and Poisson. For most parameter settings these
      assumptions are strongly violated; nevertheless, so long as the networks are not
      too synchronous, we find good agreement between mean field prediction and network
      simulations. Thus, much of the intuition developed for randomly connected
      networks in the asynchronous regime applies to mildly synchronous networks. 

PMID- 24091646
TI  - What to copy: the key factor of observational learning in striped jack
      (Pseudocaranx dentex) juveniles.
AB  - Animals in social environments can enhance their learning efficiency by observing
      the behaviour of others. Our previous study showed that learning efficiency of
      schooling fish increased through the observation of the behaviour of trained
      demonstrator conspecifics. The present study aimed to verify the key factor of
      observational learning by investigating what information is important for social
      transmission of feeding information. A striped jack (Pseudocaranx dentex)
      observer was provided with one of the five observation treatments: (a) pellets
      observation, where pellets were dropped near the aeration in an adjacent tank;
      (b) responding conspecific observation, where a trained conspecific demonstrator
      responded to the aeration without food in the adjacent tank; (c) foraging
      conspecific observation, where a conspecific demonstrator foraged near the
      aeration in the adjacent tank; (d) nearby pellets observation, where pellets were
      dropped in a transparent column near the aeration in the observer tank; and (e)
      foraging heterospecific observation, where a filefish (Stephanolepis cirrhifer)
      demonstrator foraged near the aeration in the adjacent tank. The response to the
      aeration in these observers was compared with that of controls who did not
      observe any behaviour. Only individuals who observed foraging conspecifics showed
      a response to the aeration after observing. These results suggest that observer
      fish acquire feeding information not through recognition of prey items or through
      imitation of the demonstrator, but through the vicarious reinforcement of a
      conspecific for foraging. 

PMID- 24091647
TI  - Anisotropic dry adhesive via cap defects.
AB  - We demonstrate how introducing a deliberate defect on the overhanging caps of
      strongly adhering mushroom shaped dry adhesive fibers can produce directional
      adhesion behavior. We find that the shape and location of this defect controls
      both the total adhesion force and the degree of directionality for these bio
      inspired adhesives. Linear beam theory is used to demonstrate how the application
      of a shear load to a fiber in tension can create a small compressive load to an
      asymmetric crack, thereby delaying adhesion failure and producing directional
      adhesion, and the theory is confirmed with finite element models and empirical
      data. Anisotropic adhesives have been fabricated and tested and can demonstrate
      normal adhesion force up to ~250 kPa with a shear displacement of 15 um away from
      the defect and as small as ~5 kPa when sheared the same amount towards the
      defect.

PMID- 24091645
TI  - Cell division: control of the chromosomal passenger complex in time and space.
AB  - The ultimate goal of cell division is equal transmission of the duplicated genome
      to two new daughter cells. Multiple surveillance systems exist that monitor
      proper execution of the cell division program and as such ensure stability of our
      genome. One widely studied protein complex essential for proper chromosome
      segregation and execution of cytoplasmic division (cytokinesis) is the
      chromosomal passenger complex (CPC). This highly conserved complex consists of
      Borealin, Survivin, INCENP, and Aurora B kinase, and has a dynamic localization
      pattern during mitosis and cytokinesis. Not surprisingly, it also performs
      various functions during these phases of the cell cycle. In this review, we will
      give an overview of the latest insights into the regulation of CPC localization
      and discuss if and how specific localization impacts its diverse functions in the
      dividing cell. 

PMID- 24091649
TI  - [Not Available].

PMID- 24091648
TI  - Discovering body site and severity modifiers in clinical texts.
AB  - OBJECTIVE: To research computational methods for discovering body site and
      severity modifiers in clinical texts. METHODS: We cast the task of discovering
      body site and severity modifiers as a relation extraction problem in the context
      of a supervised machine learning framework. We utilize rich linguistic features
      to represent the pairs of relation arguments and delegate the decision about the
      nature of the relationship between them to a support vector machine model. We
      evaluate our models using two corpora that annotate body site and severity
      modifiers. We also compare the model performance to a number of rule-based
      baselines. We conduct cross-domain portability experiments. In addition, we carry
      out feature ablation experiments to determine the contribution of various feature
      groups. Finally, we perform error analysis and report the sources of errors.
      RESULTS: The performance of our method for discovering body site modifiers
      achieves F1 of 0.740-0.908 and our method for discovering severity modifiers
      achieves F1 of 0.905-0.929. DISCUSSION: Results indicate that both methods
      perform well on both in-domain and out-domain data, approaching the performance
      of human annotators. The most salient features are token and named entity
      features, although syntactic dependency features also contribute to the overall
      performance. The dominant sources of errors are infrequent patterns in the data
      and inability of the system to discern deeper semantic structures. CONCLUSIONS:
      We investigated computational methods for discovering body site and severity
      modifiers in clinical texts. Our best system is released open source as part of
      the clinical Text Analysis and Knowledge Extraction System (cTAKES).

PMID- 24091650
TI  - [What did bachelard mean by "applied rationalism" ?].
AB  - Bachelard was concerned with the processes whereby scientific knowledge is
      acquired, including the activity of knowing subjects. He did not equate reasoning
      with logic but rather argued that reasoning resulted from the use of mathematics
      in organizing both thought and experimental practices, which is why he conceived
      science as applied mathematics. This had material and technical implications, for
      Bachelard was concerned with the element of reason inherent in technical
      materialism as well as the concrete reality inherent in applied rationalism. 

PMID- 24091651
TI  - [Vasile Tonoiu and the modern scientific spirit a romanian approach of Gaston
      Bachelard's work].
AB  - One of the Romanian scholars who studied extensively the work of Bachelard in
      Romania is Professor Vasile Tonoiu from the University of Bucharest. We analyze
      in this article some of his thoughts regarding the epistemology of the French
      philosopher. Even though he lacks a historical vision of the epistemological
      works of Bachelard, Tonoiu did not fail to understand the spirit of the French
      neo-rationalism, which he compared to the field of Anglo-American epistemology. 

PMID- 24091652
TI  - [Brunschvicg, bachelard and the internal logic of scientific discourse].
AB  - Bachelard is seen as sharing with Brunschvicg an "internalist" epistemology of
      mathematics and exact sciences. Brunschvicg's notion of constructive idealism
      concurs with Bachelard's surrationalism. Both philosophers defended the idea of
      an internal logic of scientific discourse which discloses the dialectics inherent
      in the dynamics of reason. The aim of philosophy is then to emphasize the genesis
      and progress of rationality in the historical development of science. 

PMID- 24091653
TI  - [Gaston Bachelard and Albert Flocon the meeting of a philosopher and an
      engraver].
AB  - The paper focuses on the collaboration between the philosopher of science Gaston
      Bachelard and the copper engraver Albert Flocon during the first decade after
      World War II. The exchange resulted in a number of books whose content is
      discussed. 

PMID- 24091654
TI  - [A material reading of Kenji Miyazawa's work].
AB  - This article offers an interpretation of Kenji Miyazawa's fairy tales using the
      theory of material imagination proposed by Gaston Bachelard. Putting Bachelard's
      theoretical framework to the test in a totally different culture, the article
      focuses on the way Japanese fairy tales make use of the four elements of
      Empedocles. These four elements in turn help to uncover an unconscious source of
      creative inspiration for Miyazawa, revealing the predominant role of earth in his
      work. 

PMID- 24091655
TI  - [Not Available].

PMID- 24091656
TI  - Weather and air pollutants have an impact on patients with respiratory diseases
      and breathing difficulties in Munich, Germany.
AB  - This study determined the influence of various meteorological variables and air
      pollutants on airway disorders in general, and asthma and/or chronic obstructive
      pulmonary disease in particular, in Munich, Bavaria, during 2006 and 2007. This
      was achieved through an evaluation of the daily frequency of calls to medical and
      emergency call centres, ambulatory medical care visits at general practitioners,
      and prescriptions of antibiotics for respiratory diseases. Meteorological
      parameters were extracted from data supplied by the European Centre for Medium
      Range Weather Forecast. Data on air pollutant levels were extracted from the air
      quality database of the European Environmental Agency for different measurement
      sites. In addition to descriptive analyses, a backward elimination procedure was
      performed to identify variables associated with medical outcome variables.
      Afterwards, generalised additive models (GAM) were used to verify whether the
      selected variables had a linear or nonlinear impact on the medical outcomes. The
      analyses demonstrated associations between environmental parameters and daily
      frequencies of different medical outcomes, such as visits at GPs and air pressure
      (-27 % per 10 hPa change) or ozone (-24 % per 10 MUg/m(3) change). The results of
      the GAM indicated that the effects of some covariates, such as carbon monoxide on
      consultations at GPs, or humidity on medical calls in general, were nonlinear,
      while the type of association varied between medical outcomes. These data suggest
      that the multiple, complex effect of environmental factors on medical outcomes
      should not be assumed homogeneous or linear a priori and that different settings
      might be associated with different types of associations. 

PMID- 24091657
TI  - Model-based indices describing cerebrovascular dynamics.
AB  - Understanding the dynamic relationship between cerebral blood flow (CBF) and the
      circulation of cerebrospinal fluid (CSF) can facilitate management of cerebral
      pathologies. For this reason, various hydrodynamic models have been introduced in
      order to simulate the phenomena governing the interaction between CBF and CSF.
      The identification of hydrodynamic models requires an array of signals as input,
      with the most common of them being arterial blood pressure, intracranial
      pressure, and cerebral blood flow velocity; monitoring all of them is considered
      as a standard practice in neurointensive care. Based on these signals,
      physiological parameters like cerebrovascular resistance, compliances of
      cerebrovascular bed, and CSF space could then be estimated. Various secondary
      model-based indices describing cerebrovascular dynamics have been introduced,
      like the cerebral arterial time constant or critical closing pressure. This
      review presents model-derived indices that describe cerebrovascular phenomena,
      the nature of which is both physiological (carbon dioxide reactivity and arterial
      hypotension) and pathological (cerebral artery stenosis, intracranial
      hypertension, and cerebral vasospasm). In a neurointensive environment, real-time
      monitoring of a patient with these indices may be able to provide a detection of
      the onset of a cerebrovascular phenomenon, which could have otherwise been
      missed. This potentially "early warning" indicator may then prove to be important
      for the therapeutic management of the patient. 

PMID- 24091658
TI  - EGFR/MEK/ERK/CDK5-dependent integrin-independent FAK phosphorylated on serine 732
      contributes to microtubule depolymerization and mitosis in tumor cells.
AB  - FAK is a non-receptor tyrosine kinase contributing to migration and proliferation
      downstream of integrin and/or growth factor receptor signaling of normal and
      malignant cells. In addition to well-characterized tyrosine phosphorylations, FAK
      is phosphorylated on several serines, whose role is not yet clarified. We
      observed that phosphorylated FAK on serine 732 (P-FAKSer732) is present at
      variable levels in vitro, in several melanoma, ovarian and thyroid tumor cell
      lines and in vivo, in tumor cells present in fresh ovarian cancer ascites. In
      vitro P-FAKSer732 was barely detectable during interphase while its levels
      strongly increased in mitotic cells upon activation of the EGFR/MEK/ERK axis in
      an integrin-independent manner. P-FAKSer732 presence was crucial for the
      maintenance of the proliferation rate and its levels were inversely related to
      the levels of acetylated alpha-tubulin. P-FAKSer732 localized at the microtubules
      (MTs) of the spindle, biochemically associated with MTs and contributed to MT
      depolymerization. The lack of the phosphorylation on Ser732 as well as the
      inhibition of CDK5 activity by roscovitine impaired mitotic spindle assembly and
      correct chromosome alignment during mitosis. We also identified, for the first
      time, that the EGF-dependent EGFR activation led to increased P-FAKSer732 and
      polymerized MTs. Our data shed light on the multifunctional roles of FAK in
      neoplastic cells, being involved not only in integrin-dependent migratory
      signaling but also in integrin-independent MT dynamics and mitosis control. These
      findings provide a new potential target for inhibiting the growth of tumor cells
      in which the EGFR/MEK/ERK/CDK5 pathway is active. 

PMID- 24091659
TI  - Necro-inflammatory response of pancreatic acinar cells in the pathogenesis of
      acute alcoholic pancreatitis.
AB  - The role of pancreatic acinar cells in initiating necro-inflammatory responses
      during the early onset of alcoholic acute pancreatitis (AP) has not been fully
      evaluated. We investigated the ability of acinar cells to generate pro- and anti
      inflammatory mediators, including inflammasome-associated IL-18/caspase-1, and
      evaluated acinar cell necrosis in an animal model of AP and human samples. Rats
      were fed either an ethanol-containing or control diet for 14 weeks and killed 3
      or 24 h after a single lipopolysaccharide (LPS) injection. Inflammasome
      components and necro-inflammation were evaluated in acinar cells by
      immunofluorescence (IF), histology, and biochemical approaches. Alcohol exposure
      enhanced acinar cell-specific production of TNFalpha, IL-6, MCP-1 and IL-10, as
      early as 3 h after LPS, whereas IL-18 and caspase-1 were evident 24 h later.
      Alcohol enhanced LPS-induced TNFalpha expression, whereas blockade of LPS
      signaling diminished TNFalpha production in vitro, indicating that the response
      of pancreatic acinar cells to LPS is similar to that of immune cells. Similar
      results were observed from acinar cells in samples from patients with
      acute/recurrent pancreatitis. Although morphologic examination of sub-clinical AP
      showed no visible signs of necrosis, early loss of pancreatic HMGB1 and increased
      systemic levels of HMGB1 and LDH were observed, indicating that this strong
      systemic inflammatory response is associated with little pancreatic necrosis.
      These results suggest that TLR-4-positive acinar cells respond to LPS by
      activating the inflammasome and producing pro- and anti-inflammatory mediators
      during the development of mild, sub-clinical AP, and that these effects are
      exacerbated by alcohol injury.

PMID- 24091660
TI  - Role of CFTR in oxidative stress and suicidal death of renal cells during
      cisplatin-induced nephrotoxicity.
AB  - The clinical use of the antineoplastic drug cisplatin is limited by its
      deleterious nephrotoxic side effect. Cisplatin-induced nephrotoxicity is
      associated with an increase in oxidative stress, leading ultimately to renal cell
      death and irreversible kidney dysfunction. Oxidative stress could be modified by
      the cystic fibrosis transmembrane conductance regulator protein (CFTR), a Cl(-)
      channel not only involved in chloride secretion but as well in glutathione (GSH)
      transport. Thus, we tested whether the inhibition of CFTR could protect against
      cisplatin-induced nephrotoxicity. Using a renal proximal cell line, we show that
      the specific inhibitor of CFTR, CFTR(inh)-172, prevents cisplatin-induced cell
      death and apoptosis by modulating the intracellular reactive oxygen species
      balance and the intracellular GSH concentration. This CFTR(inh)-172-mediated
      protective effect occurs without affecting cellular cisplatin uptake or the
      formation of platinum-DNA adducts. The protective effect of CFTR(inh)-172 in
      cisplatin-induced nephrotoxicity was also investigated in a rat model. Five days
      after receiving a single cisplatin injection (5 mg/kg), rats exhibited renal
      failure, as evidenced by the alteration of biochemical and functional parameters.
      Pretreatment of rats with CFTR(inh)-172 (1 mg/kg) prior to cisplatin injection
      significantly prevented these deleterious cisplatin-induced nephrotoxic effects.
      Finally, we demonstrate that CFTR(inh)-172 does not impair cisplatin-induced cell
      death in the cisplatin-sensitive A549 cancer cell line. In conclusion, the use of
      a specific inhibitor of CFTR may represent a novel therapeutic approach in the
      prevention of nephrotoxic side effects during cisplatin treatment without
      affecting its antitumor efficacy.

PMID- 24091661
TI  - Siramesine triggers cell death through destabilisation of mitochondria, but not
      lysosomes.
AB  - A sigma-2 receptor agonist siramesine has been shown to trigger cell death of
      cancer cells and to exhibit a potent anticancer activity in vivo. However, its
      mechanism of action is still poorly understood. We show that siramesine can
      induce rapid cell death in a number of cell lines at concentrations above 20 MUM.
      In HaCaT cells, cell death was accompanied by caspase activation, rapid loss of
      mitochondrial membrane potential (MMP), cytochrome c release, cardiolipin
      peroxidation and typical apoptotic morphology, whereas in U-87MG cells most
      apoptotic hallmarks were not notable, although MMP was rapidly lost. In contrast
      to the rapid loss of MMP above 20 MUM siramesine, a rapid increase in lysosomal
      pH was observed at all concentrations tested (5-40 MUM); however, it was not
      accompanied by lysosomal membrane permeabilisation (LMP) and the release of
      lysosomal enzymes into the cytosol. Increased lysosomal pH reduced the lysosomal
      degradation potential as indicated by the accumulation of immature forms of
      cysteine cathepsins. The lipophilic antioxidant alpha-tocopherol, but not the
      hydrophilic antioxidant N-acetyl-cysteine, considerably reduced cell death and
      destabilisation of mitochondrial membranes, but did not prevent the increase in
      lysosomal pH. At concentrations below 15 MUM, siramesine triggered cell death
      after 2 days or later, which seems to be associated with a general metabolic and
      energy imbalance due to defects in the endocytic pathway, intracellular
      trafficking and energy production, and not by a specific molecular event.
      Overall, we show that cell death in siramesine-treated cells is induced by
      destabilisation of mitochondria and is independent of LMP and the release of
      cathepsins into the cytosol. Moreover, it is unlikely that siramesine acts
      exclusively through sigma-2 receptors, but rather through multiple molecular
      targets inside the cell. Our findings are therefore of significant importance in
      designing the next generation of siramesine analogues with high anticancer
      potential.

PMID- 24091662
TI  - Opposing effects of high- and low-molecular weight hyaluronan on CXCL12-induced
      CXCR4 signaling depend on CD44.
AB  - The tumor microenvironment makes a decisive contribution to the development and
      dissemination of cancer, for example, through extracellular matrix components
      such as hyaluronan (HA), and through chemokines that regulate tumor cell behavior
      and angiogenesis. Here we report a molecular link between HA, its receptor CD44
      and the chemokine CXCL12 in the regulation of cell motility and angiogenesis.
      High-molecular-weight HA (hHA) was found to augment CXCL12-induced CXCR4
      signaling in both HepG2iso cells and primary human umbilical vein endothelial
      cells, as evidenced by enhanced ERK phosphorylation and increased cell motility.
      The augmentation of CXCR4 signaling translated into increased vessel sprouting
      and angiogenesis in a variety of assays. Small HA oligosaccharides (sHA)
      efficiently inhibited these effects. Both siRNA-mediated reduction of CD44
      expression and antibodies that block the interaction of CD44 with HA provided
      evidence that CXCL12-induced CXCR4 signaling depends on the binding of hHA to
      CD44. Consistently, CD44 and CXCR4 were found to physically interact in the
      presence of CXCL12, an interaction that could be inhibited by sHA. These findings
      provide novel insights into how microenvironmental components interact with cell
      surface receptors in multi-component complexes to regulate key aspects of tumor
      growth and progression. 

PMID- 24091663
TI  - Inhibition of oxidative stress by coenzyme Q10 increases mitochondrial mass and
      improves bioenergetic function in optic nerve head astrocytes.
AB  - Oxidative stress contributes to dysfunction of glial cells in the optic nerve
      head (ONH). However, the biological basis of the precise functional role of
      mitochondria in this dysfunction is not fully understood. Coenzyme Q10 (CoQ10),
      an essential cofactor of the electron transport chain and a potent antioxidant,
      acts by scavenging reactive oxygen species (ROS) for protecting neuronal cells
      against oxidative stress in many neurodegenerative diseases. Here, we tested
      whether hydrogen peroxide (100 MUM H2O2)-induced oxidative stress alters the
      mitochondrial network, oxidative phosphorylation (OXPHOS) complex (Cx) expression
      and bioenergetics, as well as whether CoQ10 can ameliorate oxidative stress
      mediated alterations in mitochondria of the ONH astrocytes in vitro. Oxidative
      stress triggered the activation of ONH astrocytes and the upregulation of
      superoxide dismutase 2 (SOD2) and heme oxygenase-1 (HO-1) protein expression in
      the ONH astrocytes. In contrast, CoQ10 not only prevented activation of ONH
      astrocytes but also significantly decreased SOD2 and HO-1 protein expression in
      the ONH astrocytes against oxidative stress. Further, CoQ10 prevented a
      significant loss of mitochondrial mass by increasing mitochondrial number and
      volume density and by preserving mitochondrial cristae structure, as well as
      promoted mitofilin and peroxisome-proliferator-activated receptor-gamma
      coactivator-1 protein expression in the ONH astrocyte, suggesting an induction of
      mitochondrial biogenesis. Finally, oxidative stress triggered the upregulation of
      OXPHOS Cx protein expression, as well as reduction of cellular adeonsine
      triphosphate (ATP) production and increase of ROS generation in the ONH
      astocytes. However, CoQ10 preserved OXPHOS protein expression and cellular ATP
      production, as well as decreased ROS generation in the ONH astrocytes. On the
      basis of these observations, we suggest that oxidative stress-mediated
      mitochondrial dysfunction or alteration may be an important pathophysiological
      mechanism in the dysfunction of ONH astrocytes. CoQ10 may provide new therapeutic
      potentials and strategies for protecting ONH astrocytes against oxidative stress
      mediated mitochondrial dysfunction or alteration in glaucoma and other optic
      neuropathies.

PMID- 24091664
TI  - Lithium chloride attenuates cell death in oculopharyngeal muscular dystrophy by
      perturbing Wnt/beta-catenin pathway.
AB  - Expansion of polyalanine tracts causes at least nine inherited human diseases.
      Among these, a polyalanine tract expansion in the poly (A)-binding protein
      nuclear 1 (expPABPN1) causes oculopharyngeal muscular dystrophy (OPMD). So far,
      there is no treatment for OPMD patients. Developing drugs that efficiently
      sustain muscle protection by activating key cell survival mechanisms is a major
      challenge in OPMD research. Proteins that belong to the Wnt family are known for
      their role in both human development and adult tissue homeostasis. A hallmark of
      the Wnt signaling pathway is the increased expression of its central effector,
      beta-catenin (beta-catenin) by inhibiting one of its upstream effector, glycogen
      synthase kinase (GSK)3beta. Here, we explored a pharmacological manipulation of a
      Wnt signaling pathway using lithium chloride (LiCl), a GSK-3beta inhibitor, and
      observed the enhanced expression of beta-catenin protein as well as the decreased
      cell death normally observed in an OPMD cell model of murine myoblast (C2C12)
      expressing the expanded and pathogenic form of the expPABPN1. Furthermore, this
      effect was also observed in primary cultures of mouse myoblasts expressing
      expPABPN1. A similar effect on beta-catenin was also observed when lymphoblastoid
      cells lines (LCLs) derived from OPMD patients were treated with LiCl. We believe
      manipulation of the Wnt/beta-catenin signaling pathway may represent an effective
      route for the development of future therapy for patients with OPMD.

PMID- 24091665
TI  - Patulin induces pro-survival functions via autophagy inhibition and p62
      accumulation.
AB  - Patulin (PAT) is one of the most common mycotoxins found in moldy fruits. Skin
      contact is one of the most likely exposure routes of PAT. Investigation of dermal
      toxicity of PAT is clearly needed and has been highlighted by WHO. In the present
      study, using human keratinocyte HaCaT cells as a model, we found that treatment
      with PAT caused an increased autophagosome accumulation. Measurements of
      autophagic flux demonstrated that the accumulation of autophagosomes by PAT was
      not directly due to enhanced autophagosome formation but due to inhibition of
      autophagosome degradation. Reductions in the activities of the lysosomal enzymes
      cathepsin B and cathepsin D by PAT might contribute to this inhibitory effect.
      Consistent with this, inhibition of autophagosome degradation by PAT resulted in
      accumulation of p62 that functioned as a pro-survival signal. The pro-survival
      function of p62 was found to be attributed to reactive oxygen species-mediated
      cytoprotective endoplasmic reticulum (ER) stress response. ER stress exerted
      cytoprotective effect via extracellular signal-regulated kinase1/2-dependent B
      cell CLL/lymphoma 2-associated agonist of cell death inhibitory phosphorylation.
      Given the critical role of autophagy and its substrate p62 in carcinogenesis, our
      findings may have important implications in PAT-induced skin carcinogenesis. 

PMID- 24091666
TI  - Porcine JAB1 significantly enhances apoptosis induced by staurosporine.
AB  - c-Jun activation domain-binding protein-1 (JAB1), also known as the subunit 5 of
      the COP9 signalosome, is a multifunctional protein that regulates cell
      proliferation, apoptosis and oncogenesis by interacting with and subsequently
      degrading a large number of proteins. Although human JAB1 (hJAB1) has been
      studied for a long time, studies on porcine JAB1 (pJAB1) have never been
      reported. In the present study, we cloned and characterized the pJAB1 gene. The
      genomic structure of the pJAB1 gene was determined. The open-reading frame of
      pJAB1 encoded 334 amino acids. The deduced amino acid sequence was highly similar
      to homologs in other species. Furthermore, the tertiary structure analysis and
      phylogenetic analysis indicated that JAB1 was highly conservative among species.
      pJAB1 may interact with several proteins according to protein-protein
      interactions analysis. In addition, pJAB1 was found to be universally expressed
      in porcine tissues. Subcellular localization analysis showed that GFP-pJAB1
      fusion protein distributed specifically in the cytoplasm. Flow cytometric
      analysis proved that pJAB1 significantly enhanced apoptosis induced by
      staurosporine, which at least partially depended on the activation of caspase-9
      and caspase-3. This study is useful for understanding the function of pJAB1 and
      offers a potential molecular model for the investigation of diseases related to
      hJAB1. 

PMID- 24091667
TI  - Piperlongumine induces autophagy by targeting p38 signaling.
AB  - Piperlongumine (PL), a natural product isolated from the plant species Piper
      longum L., can selectively induce apoptotic cell death in cancer cells by
      targeting the stress response to reactive oxygen species (ROS). Here we show that
      PL induces cell death in the presence of benzyloxycarbonylvalyl-alanyl-aspartic
      acid (O-methyl)-fluoro-methylketone (zVAD-fmk), a pan-apoptotic inhibitor, and in
      the presence of necrostatin-1, a necrotic inhibitor. Instead PL-induced cell
      death can be suppressed by 3-methyladenine, an autophagy inhibitor, and
      substantially attenuated in cells lacking the autophagy-related 5 (Atg5) gene. We
      further show that PL enhances autophagy activity without blocking autophagy flux.
      Application of N-acetyl-cysteine, an antioxidant, markedly reduces PL-induced
      autophagy and cell death, suggesting an essential role for intracellular ROS in
      PL-induced autophagy. Furthermore, PL stimulates the activation of p38 protein
      kinase through ROS-induced stress response and p38 signaling is necessary for the
      action of PL as SB203580, a p38 inhibitor, or dominant-negative p38 can
      effectively reduce PL-mediated autophagy. Thus, we have characterized a new
      mechanism for PL-induced cell death through the ROS-p38 pathway. Our findings
      support the therapeutic potential of PL by triggering autophagic cell death. 

PMID- 24091668
TI  - A NANOS3 mutation linked to protein degradation causes premature ovarian
      insufficiency.
AB  - Primary ovarian insufficiency (POI), or premature ovarian failure, is defined as
      the cessation of ovarian function before the age of 40. An insufficient ovarian
      follicle pool derived from primordial germ cells (PGCs) is an important cause of
      POI. Although the Nanos gene family is known to be required for PGC development
      and maintenance in diverse model organisms, the relevance of this information to
      human biology is not yet clear. In this study, we screened the coding regions of
      the NANOS1, NANOS2 and NANOS3 genes in 100 Chinese POI patients and identified
      four variants in the coding regions of these three genes, including one
      synonymous variant in NANOS3, one missense variant in each of NANOS1 and NANOS2
      and one potentially relevant mutation (c.457C>T; p.Arg153Trp, heterozygous) in
      NANOS3. We demonstrated that the p.Arg153Trp substitution decreases the stability
      of NANOS3, potentially resulting in a hypomorph. Furthermore, an investigation of
      the relationship between the number of PGCs and the dosage of NANOS3 in mouse
      models showed that the population of PGCs is controlled by the level of NANOS3
      protein. Taken together, our results provide new insight into the properties of
      the NANOS3 protein and establish that NANOS3 mutation is one possible cause of
      POI. 

PMID- 24091669
TI  - Calreticulin surface exposure is abrogated in cells lacking, chaperone-mediated
      autophagy-essential gene, LAMP2A.

PMID- 24091670
TI  - PI3K/mTOR pathway inhibitors sensitize chronic myeloid leukemia stem cells to
      nilotinib and restore the response of progenitors to nilotinib in the presence of
      stem cell factor.
AB  - Nilotinib is a second-generation tyrosine kinase inhibitor, designed to
      specifically inhibit break-point cluster region (BCR)-Abelson (ABL) and developed
      to treat chronic myeloid leukemia (CML) in patients showing a resistance to
      imatinib. We previously demonstrated that nilotinib-induced apoptosis was reduced
      by stem cell factor (SCF) addition. Here, the SCF-activated survival pathway was
      investigated. BCR-ABL expression was accompanied by the activation of the SCF
      receptor: c-KIT. Nilotinib inhibited this activation that was restored by SCF
      binding. Parallel variations were observed for mammaliam target of rapamycin
      (mTOR) kinase and mTOR complex 1 substrate S6K. The inhibition of mTORC1 restored
      the response of BCR-ABL cell lines to nilotinib in the presence of SCF. PI3K
      inhibition restored nilotinib-induced apoptosis. On hematopoietic progenitors
      from CML patient's bone marrows, mTORC1 inhibition also restored nilotinib
      sensitivity in the presence of SCF, confirming its involvement in SCF-activated
      survival pathway. However, this pathway seems not to be involved in the nilotinib
      induced resistance of the CML stem cell population. Conversely, PI3K inhibition
      sensitized both CML progenitors and stem cells to nilotinib, suggesting that,
      downstream PI3K, two different kinase pathways are activated in CML progenitor
      and stem cell populations. 

PMID- 24091671
TI  - Cancer-initiating cells derived from human rectal adenocarcinoma tissues carry
      mesenchymal phenotypes and resist drug therapies.
AB  - Accumulating evidence indicates that cancer-initiating cells (CICs) are
      responsible for cancer initiation, relapse, and metastasis. Colorectal carcinoma
      (CRC) is typically classified into proximal colon, distal colon, and rectal
      cancer. The gradual changes in CRC molecular features within the bowel may have
      considerable implications in colon and rectal CICs. Unfortunately, limited
      information is available on CICs derived from rectal cancer, although colon CICs
      have been described. Here we identified rectal CICs (R-CICs) that possess
      differentiation potential in tumors derived from patients with rectal
      adenocarcinoma. The R-CICs carried both CD44 and CD54 surface markers, while R
      CICs and their immediate progenies carried potential epithelial-mesenchymal
      transition characteristics. These R-CICs generated tumors similar to their tumor
      of origin when injected into immunodeficient mice, differentiated into rectal
      epithelial cells in vitro, and were capable of self-renewal both in vitro and in
      vivo. More importantly, subpopulations of R-CICs resisted both 5
      fluorouracil/calcium folinate/oxaliplatin (FolFox) and cetuximab treatment, which
      are the most common therapeutic regimens used for patients with advanced or
      metastatic rectal cancer. Thus, the identification, expansion, and properties of
      R-CICs provide an ideal cellular model to further investigate tumor progression
      and determine therapeutic resistance in these patients. 

PMID- 24091672
TI  - P2X7 purinoceptors contribute to the death of Schwann cells transplanted into the
      spinal cord.
AB  - The potential to use Schwann cells (SCs) in neural repair for patients suffering
      from neurotrauma and neurodegenerative diseases is well recognized. However,
      significant cell death after transplantation hinders the clinical translation of
      SC-based therapies. Various factors may contribute to the death of transplanted
      cells. It is known that prolonged activation of P2X7 purinoceptors (P2X7R) can
      lead to death of certain types of cells. In this study, we show that rat SCs
      express P2X7R and exposure of cultured SCs to high concentrations of ATP (3-5 mM)
      or a P2X7R agonist, 2'(3')-O-(4-benzoylbenzoyl)ATP (BzATP) induced significant
      cell death rapidly. High concentrations of ATP and BzATP increased ethidium
      uptake by SCs, indicating increased membrane permeability to large molecules, a
      typical feature of prolonged P2X7R activation. SC death, as well as ethidium
      uptake, induced by ATP was blocked by an irreversible P2X7R antagonist oxidized
      ATP (oxATP) or a reversible P2X7R antagonist A438079. oxATP also significantly
      inhibits the increase of intracellular free calcium induced by minimolar ATP
      concentrations. Furthermore, ATP did not cause death of SCs isolated from P2X7R
      knockout mice. All these results suggest that P2X7R is responsible for ATP
      induced SC death in vitro. When rat SCs were treated with oxATP before
      transplantation into uninjured rat spinal cord, 35% more SCs survived than
      untreated SCs 1 week after transplantation. Moreover, 58% more SCs isolated from
      P2X7R-knockout mice survived after being transplanted into rat spinal cord than
      SCs from wild-type mice. This further confirms that P2X7R is involved in the
      death of transplanted SCs. These results indicate that targeting P2X7R on SCs
      could be a potential strategy to improve the survival of transplanted cells. As
      many other types of cells, including neural stem cells, also express P2X7R,
      deactivating P2X7R may improve the survival of other types of transplanted cells.

PMID- 24091673
TI  - Asymmetric dimethylarginine attenuates serum starvation-induced apoptosis via
      suppression of the Fas (APO-1/CD95)/JNK (SAPK) pathway.
AB  - Asymmetric dimethylarginine (ADMA) is synthesized by protein arginine
      methyltransferases during methylation of protein arginine residues and released
      into blood upon proteolysis. Higher concentrations of ADMA in blood have been
      observed in patients with metabolic diseases and certain cancers. However, the
      role of ADMA in colon cancer has not been well investigated. ADMA serum levels in
      human patients diagnosed with colon cancer were found to be higher than those
      present in healthy subjects. ADMA treatment of LoVo cells, a human colon
      adenocarcinoma cell line, attenuated serum starvation-induced apoptosis and
      suppressed the activation of the Fas (APO-1/CD95)/JNK (SAPK) (c-Jun N terminal
      protein kinase/stress-activated protein kinase)pathway. ADMA also suppressed the
      activation of JNK triggered by death receptor ligand anti-Fas mAb and exogenous
      C2-ceramide. Moreover, we demonstrated that ADMA pretreatment protected LoVo
      cells from doxorubicin hydrochloride-induced cell death and activation of the
      Fas/JNK pathway. In summary, our results suggest that the elevated ADMA in colon
      cancer patients may contribute to the blocking of apoptosis of cancer cells in
      response to stress and chemotherapy. 

PMID- 24091674
TI  - Epithelial-mesenchymal transition markers expressed in circulating tumor cells in
      hepatocellular carcinoma patients with different stages of disease.
AB  - The presence of circulating tumor cells (CTCs) in peripheral blood is associated
      with metastasis and prognosis in hepatocellular carcinoma (HCC) patients. The
      epithelial-mesenchymal transition (EMT) has a pivotal role in tumor invasion and
      dissemination. To identify more sensitive biomarkers for evaluating metastasis
      and prognosis, we investigated the expression of EMT markers, including vimentin,
      twist, ZEB1, ZEB2, snail, slug and E-cadherin in CTCs, primary HCC tumors and
      adjacent non-tumoral liver tissues. After isolating viable CTCs from the
      peripheral blood of HCC patients using asialoglycoprotein receptors (ASGPRs), the
      CTCs were identified with immunofluorescence staining. CTCs were detected in the
      peripheral blood obtained from 46 of 60 (76.7%) HCC patients. Triple
      immunofluorescence staining showed that twist and vimentin expression could be
      detected in CTCs obtained from 39 (84.8%) and 37 (80.4%) of the 46 patients,
      respectively. The expression of both twist and vimentin in CTCs was significantly
      correlated with portal vein tumor thrombus. Coexpression of twist and vimentin in
      CTCs could be detected in 32 (69.6%) of the 46 patients and was highly correlated
      with portal vein tumor thrombus, TNM classification and tumor size. Quantitative
      fluorescence western blot analysis revealed that the expression levels of E
      cadherin, vimentin and twist in HCC tumors were significantly associated with the
      positivity of isolated CTCs (P=0.013, P=0.012, P=0.009, respectively). However,
      there was no significant difference in ZEB1, ZEB2, snail and slug expression
      levels in CTCs, primary HCC tumors and adjacent non-tumoral liver tissues across
      samples with regard to the clinicopathological parameters. Our results
      demonstrate that the EMT has a role in promoting the blood-borne dissemination of
      primary HCC cells, and the twist and vimentin expression levels in CTCs could
      serve as promising biomarkers for evaluating metastasis and prognosis in HCC
      patients. 

PMID- 24091675
TI  - Dexamethasone shifts bone marrow stromal cells from osteoblasts to adipocytes by
      C/EBPalpha promoter methylation.
AB  - Dexamethasone (Dex)-induced osteoporosis has been described as the most severe
      side effect in long-term glucocorticoid therapy. The decreased bone mass and the
      increased marrow fat suggest that Dex possibly shifts the differentiation of bone
      marrow stromal cells (BMSCs) to favor adipocyte over osteoblast, but the
      underlying mechanisms are still unknown. In this paper, we established a Dex
      induced osteoporotic mouse model, and found that BMSCs from Dex-treated mice are
      more likely to differentiate into adipocyte than those from control mice, even
      under the induction of bone morphogenetic protein-2 (BMP2). We also discovered
      both in vitro and in vivo that the expression level of adipocyte regulator
      CCAAT/enhancer-binding protein alpha (C/EBPalpha) is significantly upregulated in
      Dex-induced osteoporotic BMSCs during osteoblastogenesis by a mechanism that
      involves inhibited DNA hypermethylation of its promoter. Knockdown of C/EBPalpha
      in Dex-induced osteoporotic cells rescues their differentiation potential,
      suggesting that Dex shifts BMSC differentiation by inhibiting C/EBPalpha promoter
      methylation and upregulating its expression level. We further found that the
      Wnt/beta-catenin pathway is involved in Dex-induced osteoporosis and C/EBPalpha
      promoter methylation, and its activation by LiCl rescues the effect of Dex on
      C/EBPalpha promoter methylation and osteoblast/adipocyte balance. This study
      revealed the C/EBPalpha promoter methylation mechanism and evaluated the function
      of Wnt/beta-catenin pathway in Dex-induced osteoporosis, providing a useful
      therapeutic target for this type of osteoporosis. 

PMID- 24091676
TI  - Suppression of polyglutamine protein toxicity by co-expression of a heat-shock
      protein 40 and a heat-shock protein 110.
AB  - A network of heat-shock proteins mediates cellular protein homeostasis, and has a
      fundamental role in preventing aggregation-associated neurodegenerative diseases.
      In a Drosophila model of polyglutamine (polyQ) disease, the HSP40 family protein,
      DNAJ-1, is a superior suppressor of toxicity caused by the aggregation of polyQ
      containing proteins. Here, we demonstrate that one specific HSP110 protein, 70
      kDa heat-shock cognate protein cb (HSC70cb), interacts physically and genetically
      with DNAJ-1 in vivo, and that HSC70cb is necessary for DNAJ-1 to suppress
      polyglutamine-induced cell death in Drosophila. Expression of HSC70cb together
      with DNAJ-1 significantly enhanced the suppressive effects of DNAJ-1 on polyQ
      induced neurodegeneration, whereas expression of HSC70cb alone did not suppress
      neurodegeneration in Drosophila models of either general polyQ disease or
      Huntington's disease. Furthermore, expression of a human HSP40, DNAJB1, together
      with a human HSP110, APG-1, protected cells from polyQ-induced neural
      degeneration in flies, whereas expression of either component alone had little
      effect. Our data provide a functional link between HSP40 and HSP110 in
      suppressing the cytotoxicity of aggregation-prone proteins, and suggest that
      HSP40 and HSP110 function together in protein homeostasis control.

PMID- 24091677
TI  - Critical role of anti-apoptotic Bcl-2 protein phosphorylation in mitotic death.
AB  - Microtubule inhibiting agents (MIAs) characteristically induce phosphorylation of
      the major anti-apoptotic Bcl-2 family members Mcl-1, Bcl-2 and Bcl-xL, and
      although this leads to Mcl-1 degradation, the role of Bcl-2/Bcl-xL
      phosphorylation in mitotic death has remained controversial. This is in part due
      to variation in MIA sensitivity among cancer cell lines, the dependency of cell
      fate on drug concentration and uncertainty about the modes of cell death
      occurring, thus making comparisons of published reports difficult. To circumvent
      problems associated with MIAs, we used siRNA knockdown of the anaphase-promoting
      complex activator, Cdc20, as a defined molecular system to investigate the role,
      specifically in mitotic death, of individual anti-apoptotic Bcl-2 proteins and
      their phosphorylated forms. We show that Cdc20 knockdown in HeLa cells induces
      mitotic arrest and subsequent mitotic death. Knockdown of Cdc20 in HeLa cells
      stably overexpressing untagged wild-type Bcl-2, Bcl-xL or Mcl-1 promoted
      phosphorylation of the overexpressed proteins in parallel with their endogenous
      counterparts. Overexpression of Bcl-2 or Bcl-xL blocked mitotic death induced by
      Cdc20 knockdown; phospho-defective mutants were more protective than wild-type
      proteins, and phospho-mimic Bcl-xL was unable to block mitotic death.
      Overexpressed Mcl-1 failed to protect from Cdc20 siRNA-mediated death, as the
      overexpressed protein was susceptible to degradation similar to endogenous Mcl-1.
      These results provide compelling evidence that phosphorylation of anti-apoptotic
      Bcl-2 proteins has a critical role in regulation of mitotic death. These findings
      make an important contribution toward our understanding of the molecular
      mechanisms of action of MIAs, which is critical for their rational use
      clinically. 

PMID- 24091678
TI  - Drugs to cure avian influenza infection--multiple ways to prevent cell death.
AB  - New treatments and new drugs for avian influenza virus (AIV) infection are
      developed continually, but there are still high mortality rates. The main reason
      may be that not all cell death pathways induced by AIV were blocked by the
      current therapies. In this review, drugs for AIV and associated acute respiratory
      distress syndrome (ARDS) are summarized. The roles of antioxidant (vitamin C) and
      multiple immunomodulators (such as Celecoxib, Mesalazine and Eritoran) are
      discussed. The clinical care of ARDS may result in ischemia reperfusion injury to
      poorly ventilated alveolar cells. Cyclosporin A should effectively inhibit this
      kind of damages and, therefore, may be the key drug for the survival of patients
      with virus-induced ARDS. Treatment with protease inhibitor Ulinastatin could also
      protect lysosome integrity after the infection. Through these analyses, a large
      drug combination is proposed, which may hypothetically greatly reduce the
      mortality rate. 

PMID- 24091679
TI  - Total keratin 18 measurements in patients following orthotopic liver
      transplantation: what is the most suitable diagnostic assay?

PMID- 24091681
TI  - P-selectin glycoprotein ligand-1 deficiency augments G-CSF induced myeloid cell
      mobilization.
AB  - The effect of granulocyte colony-stimulating factor (G-CSF) was investigated in P
      selectin glycoprotein ligand-1 (PSGL-1) deficient (PSGL-1(-/-)) and wild-type
      (PSGL-1(+/+)) mice to establish the role of this mucin in myeloid cell
      mobilization. G-CSF activates tissue proteases that cleave adhesion molecules,
      thus enhances the mobilization of myeloid cells and haematopoietic stem cells.
      Cytopenia was induced with a single dose of cyclophosphamide. In PSGL-1(-/-)
      animals, we observed a delayed extravasation of mature myeloid cells from the
      peripheral vessels into the tissue compartments and their faster mobilization
      from the bone marrow. Subsequently, animals received G-CSF twice a day for 4
      days. Neutrophil and monocyte counts increased upon completion of G-CSF treatment
      and both values were significantly higher in PSGL-1(-/-) mice; 47.7 versus 28.3
      G/l for neutrophils and 4.1 versus 2.0 G/l for monocytes. The ratio of atypical
      myeloid cells was also elevated. Analyzing the causes of the above differences,
      we identified a 4-fold increase in the colony-forming unit (CFU-GM) counts of the
      peripheral blood in PSGL-1(-/-) mice, compared to wild-type animals. A
      significantly elevated number of CFU-GM was detected also in the femurs of PSGL
      1(-/-) mice, 4 and 5 days after cyclophosphamide treatment and these values
      paralleled with the elevation of CD34+/CD117+ stem cell counts in the peripheral
      blood. Our data suggest, that in the absence of PSGL-1, G-CSF was more potent in
      elevating absolute myeloid cell numbers by acting on cell release from the bone
      marrow, maturation from circulating precursor cells in the peripheral blood and
      prolonged retainment in the circulation. 

PMID- 24091682
TI  - Mycotoxicoses of ruminants and horses.
AB  - In the current study, mycotoxicoses of ruminants and horses are reviewed, with an
      emphasis on the occurrence of these diseases in South America. The main
      mycotoxicoses observed in grazing cattle include intoxications by indole
      diterpenoid mycotoxins (Paspalum spp. contaminated by Claviceps paspali, Lolium
      perenne infected by Neotyphodium lolii, Cynodon dactylon infected by Claviceps
      cynodontis, and Poa huecu), gangrenous ergotism and dysthermic syndrome
      (hyperthermia) caused by Festuca arundinacea (syn. Festuca elatior) infected by
      Neotyphodium coenophialum (syn. Acremonium coenophialum), and photosensitization
      in pastures contaminated by toxigenic Pithomyces chartarum. Other mycotoxicoses
      in grazing cattle include slaframine toxicity in clover pastures infected by
      Rhizoctonia leguminicola and diplodiosis in cattle grazing in corn stubbles. The
      mycotoxicoses caused by contaminated concentrated food or byproducts in cattle
      include poisoning by toxins of Aspergillus clavatus, which contaminate barley or
      sugar beetroot by-products, gangrenous ergotism or dysthermic syndrome caused by
      wheat bran or wheat screenings contaminated with Claviceps purpurea, and acute
      respiratory distress caused by damaged sweet potatoes (Ipomoea batatas). The main
      mycotoxicosis of horses is leukoencephalomalacia caused by the fumonisins B1 and
      B2 produced by Fusarium spp. Poisoning by C. purpurea and F. elatior infected by
      N. coenophialum has also been reported as a cause of agalactia and neonatal
      mortality in mares. Slaframine toxicosis caused by the ingestion of alfalfa hay
      contaminated by R. leguminicola has also been reported in horses.

PMID- 24091683
TI  - Development and performance evaluation of a streamlined method for nucleic acid
      purification, denaturation, and multiplex detection of Bluetongue virus and
      Epizootic hemorrhagic disease virus.
AB  - Bluetongue virus (BTV) and Epizootic hemorrhagic disease virus (EHDV) possess
      similar structural and molecular features, are transmitted by biting midges
      (genus Culicoides), and cause similar diseases in some susceptible ruminants.
      Generally, BTV causes subclinical disease in cattle, characterized by a prolonged
      viremia. EHDV-associated disease in cattle is less prominent; however, it has
      emerged as a major economic threat to the white-tailed deer (Odocoileus
      virginianus) industry in many areas of the United States. The recent emergence of
      multiple BTV and EHDV serotypes previously undetected in the United States
      demonstrates the need for robust detection of all known serotypes and
      differential diagnosis. For this purpose, a streamlined workflow consisting of an
      automated nucleic acid purification and denaturation method and a multiplex one
      step reverse transcription quantitative polymerase chain reaction for the
      simultaneous detection of BTV serotypes 1-24 and EHDV serotypes 1-7 was developed
      using previously published BTV and EHDV assays. The denaturation of double
      stranded (ds) BTV and EHDV RNA was incorporated into the automated nucleic acid
      purification process thus eliminating the commonly used separate step of dsRNA
      denaturation. The performance of this workflow was compared with the World
      Organization of Animal Health BTV reference laboratory (National Veterinary
      Services Laboratory, Ames, Iowa) workflow for BTV and EHDV detection, and high
      agreement was observed. Implementation of the workflow in routine diagnostic
      testing enables the detection of, and differentiation between, BTV and EHDV, and
      coinfections in bovine blood and cervine tissues, offering significant benefits
      in terms of differential disease diagnosis, herd health monitoring, and regulated
      testing. 

PMID- 24091684
TI  - Function of lncRNAs and approaches to lncRNA-protein interactions.
AB  - Long non-coding RNAs (lncRNAs), which represent a new frontier in molecular
      biology, play important roles in regulating gene expression at epigenetic,
      transcriptional and post-transcriptional levels. More and more lncRNAs have been
      found to play important roles in normal cell physiological activities, and
      participate in the development of varieties of tumors and other diseases.
      Previously, we have only been able to determine the function of lncRNAs through
      multiple mechanisms, including genetic imprinting, chromatin remodeling, splicing
      regulation, mRNA decay, and translational regulation. Application of
      technological advances to research into the function of lncRNAs is extremely
      important. The major tools for exploring lncRNAs include microarrays, RNA
      sequencing (RNA-seq), Northern blotting, real-time quantitative reverse
      transcription-polymerase chain reaction (qRT-PCR), fluorescence in situ
      hybridization (FISH), RNA interference (RNAi), RNA-binding protein
      immunoprecipitation (RIP), chromatin isolation by RNA purification (ChIRP),
      crosslinking-immunopurification (CLIP), and bioinformatic prediction. In this
      review, we highlight the functions of lncRNAs, and advanced methods to research
      lncRNA-protein interactions.

PMID- 24091685
TI  - Non-coding RNAs regulate tumor cell plasticity.
AB  - Tumor metastasis is one of the most serious challenges for human cancers as the
      majority of deaths caused by cancer are associated with metastasis, rather than
      the primary tumor. Recent studies have demonstrated that tumor cell plasticity
      plays a critical role in tumor metastasis by giving rise to various cell types
      which is necessary for tumor to invade adjacent tissues and form distant
      metastasis. These include differentiation of cancer stem cells (CSCs), or
      epithelial-mesenchymal transition (EMT) and its reverse process, mesenchymal
      epithelial transition (MET). A growing body of evidence has demonstrated that the
      biology of tumor cell plasticity is tightly linked to functions of non-coding
      RNAs (ncRNAs), especially microRNAs (miRNAs) and long non-coding RNAs (lncRNAs).
      Therefore, understanding the mechanisms how non-coding RNAs regulate tumor cell
      plasticity is essential for discovery of new diagnostic markers and therapeutic
      targets to overcome metastasis.

PMID- 24091686
TI  - Long non-coding RNA-guided regulation in organisms.
AB  - It is clear that RNA is more than just a messenger between gene and protein. The
      mammalian genome is pervasively transcribed, giving rise to tens of thousands of
      non-coding transcripts. Whether all of these transcripts are functional remains
      to be elucidated, but it is evident that there are many functional long non
      coding RNAs (lncRNAs). Recent studies have set out to decode the regulatory role
      and functional diversity of lncRNAs. Here we organize these studies to highlight
      the significant involvements of lncRNAs in regulation of gene expression and
      human physiological and pathological processes, which are achieved by their
      interaction with DNA, RNA or protein.

PMID- 24091687
TI  - Large-scale study of long non-coding RNA functions based on structure and
      expression features.
AB  - Mammals and other complex organisms can transcribe an abundance of long non
      coding RNAs (lncRNAs) that fulfill a wide variety of regulatory roles in many
      biological processes. These roles, including as scaffolds and as guides for
      protein-coding genes, mainly depend on the structure and expression level of
      lncRNAs. In this review, we focus on the current methods for analyzing lncRNA
      structure and expression, which is basic but necessary information for in-depth,
      large-scale analysis of lncRNA functions.

PMID- 24091688
TI  - Transcriptomics: advances and approaches.
AB  - Transcriptomics is one of the most developed fields in the post-genomic era.
      Transcriptome is the complete set of RNA transcripts in a specific cell type or
      tissue at a certain developmental stage and/or under a specific physiological
      condition, including messenger RNA, transfer RNA, ribosomal RNA, and other non
      coding RNAs. Transcriptomics focuses on the gene expression at the RNA level and
      offers the genome-wide information of gene structure and gene function in order
      to reveal the molecular mechanisms involved in specific biological processes.
      With the development of next-generation high-throughput sequencing technology,
      transcriptome analysis has been progressively improving our understanding of RNA
      based gene regulatory network. Here, we discuss the concept, history, and
      especially the recent advances in this inspiring field of study. 

PMID- 24091689
TI  - Peak bone mass in young HIV-infected patients compared with healthy controls.
AB  - INTRODUCTION: Peak bone mass (PBM) is the amount of bone present at the end of
      skeletal maturation. It is an important determinant of osteoporotic fracture
      risk. Data on the PBM in the HIV-infected population are lacking. DESIGN AND
      METHODS: We performed a multicenter (6 centers in Spain), case-control study to
      assess PBM using dual-energy x-ray absorptiometry. We studied HIV-infected
      patients aged 20-30 years and compared them with age- and gender-matched non-HIV
      infected controls. We also assessed the predictive factors for a low PBM.
      RESULTS: We included 307 subjects: 232 HIV-infected patients and 75 non-HIV
      infected controls. Bone mineral density was similar in both groups although
      differences were seen in the total femur T-score (-0.15SD versus +0.50SD,
      respectively, P = 0.018). The percentage of osteopenia and osteoporosis was
      higher in the HIV-infected patients (56.5% and 10.7%, respectively) than in the
      controls (50.7% and 4%, respectively; P = 0.019). Osteoporosis was more frequent
      in HIV-infected men than in control men and HIV-infected women (12.2% versus 5.5%
      and 4.8%, P = 0.033). Protease inhibitors and nadir CD4 T-cells were negatively
      associated with PBM, whereas fat and lean mass were positively associated with
      PBM. CONCLUSIONS: Bone mineral density was similar between HIV-infected patients
      aged 20-30 years than in age- and gender-matched controls. However, lower femoral
      T-scores and higher rate of osteopenia and osteoporosis were seen in HIV-infected
      men. Therapy with protease inhibitors, nadir CD4 counts, and fat and lean mass
      were predictive factors of PBM. Given that these patients will be living with HIV
      infection for many years, every effort should be made to modify risk factors.

PMID- 24091690
TI  - The role of HIV and monocytes/macrophages in adipose tissue biology.
AB  - OBJECTIVE: To assess the role of HIV and monocytes/macrophages in adipose tissue
      dysregulation. METHODS: Cross-sectional study in 5 groups: HIV seronegative, HIV+
      antiretroviral therapy (ART)-naive, HIV+ nonlipoatrophic on zidovudine- and/or
      stavudine-containing ART, HIV+ lipoatrophic on similar ART, and HIV+ on abacavir-
      or tenofovir-containing ART. HIV DNA in circulating monocyte subsets was
      quantitated by real-time polymerase chain reaction. Biopsied subcutaneous fat was
      examined for macrophage content by CD68 staining. Isolated adipocytes and
      macrophages were cultured and the supernatant assayed for secretory products by
      Luminex multiplex cytokine technology. RESULTS: Sixty-nine subjects were
      enrolled. Lipoatrophic subjects had higher median HIV DNA levels (270.5 copies/10
      cells) in circulating peripheral CD14CD16 co-expressing monocyte subsets compared
      with subjects who were ART-naive (25.0 copies), nonlipoatrophic (15.0 copies), or
      on abacavir/tenofovir (57.5 copies), P < 0.01. Group differences in adipocytes
      and adipose macrophage content were marginal. Although adipocyte secretory
      products were similar, HIV-infected subjects had higher adipose macrophage
      derived interleukin (IL)-12p40, IL-6, IL-8, and monocyte inflammatory protein 1
      alpha and lower eotaxin and interferon gamma levels than HIV seronegative
      subjects (P < 0.05). Within HIV-infected subjects, adipose macrophage secretory
      products were comparable between subjects naive with ART versus those on ART.
      CONCLUSIONS: Circulating HIV-infected and proinflammatory CD14CD16 monocyte
      subsets contribute to the pathogenesis of HIV-associated lipoatrophy. Among HIV
      infected individuals, macrophages, rather than adipocytes, are the primary source
      of low-grade inflammation in subcutaneous adipose tissue. HIV infection modifies
      these macrophages to a more proinflammatory phenotype, and these changes are not
      substantially mitigated by the use of ART.

PMID- 24091691
TI  - Exploring the relationship between incarceration and HIV among black men who have
      sex with men in the United States.
AB  - This study examined the predictors of new incarceration and their association
      with HIV infection among 1278 black men who have sex with men enrolled and
      followed up in the HIV Prevention Trials Network 061 study. HIV Prevention Trials
      Network 061 was conducted to determine the feasibility and acceptability of a
      multicomponent intervention to reduce HIV infection among BMSM in 6 US cities. In
      this study, multivariable logistic regression models were used to explore the
      association between incarceration during study follow-up and several demographic,
      behavioral, and psychosocial variables at baseline found to be significant in
      bivariate analyses. In addition, Cox proportional hazard regression was used to
      explore the association between incarceration during study follow-up and incident
      HIV infection. Among the 1278 BMSM with follow-up data, 305 (24%) reported a new
      incarceration within 1 year of entering the study with an estimated incarceration
      incidence of 35% (95% confidence interval: 31% to 38%). After adjusting for
      confounders, lower education, lower annual income, previous incarceration
      frequency, and higher levels of perceived racism were significantly associated
      with new incarcerations during study follow-up. There was no observed association
      between incarceration during study follow-up and incident HIV infection. The very
      high level of new incarcerations highlights the importance of structural-level
      interventions to prevent incarceration among economically disenfranchised black
      men who have sex with men in the United States.

PMID- 24091692
TI  - Integration and task shifting for TB/HIV care and treatment in highly resource
      scarce settings: one size may not fit all.
AB  - BACKGROUND: A crucial question in managing HIV-infected patients with
      tuberculosis (TB) concerns when and how to initiate antiretroviral therapy (ART).
      The effectiveness of CD4-stratified ART initiation in a nurse-centered,
      integrated TB/HIV program at primary care in Kinshasa, Democratic Republic of
      Congo, was assessed. METHODS: Prospective cohort study was conducted to assess
      the effect of CD4-stratified ART initiation by primary care nurses (513 TB
      patients, August 2007 to November 2009). ART was to be initiated at 1 month of TB
      treatment if CD4 count is <100 cells per cubic millimeter, at 2 months if CD4
      count is 100-350 cells per cubic millimeter, and at the end of TB treatment after
      CD4 count reassessment if CD4 count is >350 cells per cubic millimeter. ART
      uptake and mortality were compared with a historical prospective cohort of 373
      HIV-infected TB patients referred for ART to a centralized facility and 3577 HIV
      negative TB patients (January 2006 to May 2007). RESULTS: ART uptake increased
      (17%-69%, P < 0.0001) and mortality during TB treatment decreased (20.1% vs 9.8%,
      P < 0.0003) after decentralized, nurse-initiated, CD4-stratified ART. Mortality
      among TB patients with CD4 count >100 cells per cubic millimeter was similar to
      that of HIV-negative TB patients (5.6% vs 6.3%, P = 0.65), but mortality among
      those with CD4 count <100 cells per cubic millimeter remained high (18.8%).
      CONCLUSIONS: Nurse-centered, CD4-stratified ART initiation at primary care level
      was effective in increasing timely ART uptake and reducing mortality among TB
      patients but may not be adequate to prevent mortality among those presenting with
      severe immunosuppression. Further research is needed to determine the optimal
      management at primary care level of TB patients with CD4 counts <100 cells per
      cubic millimeter.

PMID- 24091693
TI  - Impact of CMV therapy with valganciclovir on immune activation and the HIV viral
      load in semen and blood: an observational clinical study.
AB  - BACKGROUND: The HIV RNA viral load (VL) in vaginal secretions and semen is an
      independent predictor of HIV transmission. Blood VL is associated with semen VL,
      and local mucosal factors, such as semen cytomegalovirus (CMV) reactivation, may
      play an important role. METHODS: Twenty-one HIV-CMV-coinfected, antiretroviral
      naive men received 900 mg of oral valganciclovir once daily for 2 weeks in an
      open-label study. Blood and semen were collected at baseline, after 2 weeks of
      valganciclovir, and 2 months after therapy completion. The primary end point was
      change in semen HIV levels at 2 weeks, and the secondary end points were change
      in semen HIV VL at 2 months and change in semen CMV levels. RESULTS: The HIV VLs
      fell significantly at 2 weeks in semen (median 3.44-3.02 log10 copies/mL, P =
      0.02) and blood (median 3.61-3.10 log10 copies/mL, P < 0.01) and returned to
      baseline after therapy completion (median 3.24 and 3.71 log10 copies/mL in semen
      and blood, respectively). Semen CMV levels also fell on treatment (median 2.13
      1.62 log10 copies/mL, P < 0.01) and continued to fall after therapy completion
      (median 0.91 log10 copies/mL at week 8, P < 0.001 vs. baseline). The reduced
      semen CMV VL was associated with decreased semen T-cell activation and enhanced
      CMV-specific T-cell responses in blood; changes in the semen HIV VL were not
      associated with immune parameters. CONCLUSIONS: Although valganciclovir therapy
      was associated with reduced HIV and semen CMV levels, these results suggest that
      the reduced HIV VL was a direct drug effect rather than a CMV antiviral effect or
      CMV-associated immune alterations.

PMID- 24091695
TI  - Nonvertical (horizontal) route of HIV transmission in children.

PMID- 24091694
TI  - Immunogenicity of ALVAC-HIV vCP1521 in infants of HIV-1-infected women in Uganda
      (HPTN 027): the first pediatric HIV vaccine trial in Africa.
AB  - OBJECTIVE: Maternal-to-child-transmission of HIV-1 infection remains a
      significant cause of HIV-1 infection despite successful prevention strategies.
      Testing protective HIV-1 vaccines remains a critical priority. The immunogenicity
      of ALVAC-HIV vCP1521 (ALVAC) in infants born to HIV-1-infected women in Uganda
      was evaluated in the first pediatric HIV-1 vaccine study in Africa. DESIGN: HIV
      Prevention Trials Network 027 was a randomized, double-blind, placebo-controlled
      phase I trial to evaluate the safety and immunogenicity of ALVAC in 60 infants
      born to HIV-1-infected mothers with CD4 counts of >500 cells per microliter,
      which were randomized to the ALVAC vaccine or placebo. ALVAC-HIV vCP1521 is an
      attenuated recombinant canarypox virus expressing HIV-1 clade E env, clade B gag,
      and protease gene products. METHODS: Infants were vaccinated at birth and 4, 8,
      and 12 weeks of age with ALVAC or placebo. Cellular and humoral immune responses
      were evaluated using interferon-gamma enzyme-linked immunosorbent spot,
      carboxyfluorescein diacetate succinimidyl ester proliferation, intracellular
      cytokine staining, and binding and neutralizing antibody assays. Fisher exact
      test was used to compare positive responses between the study arms. RESULTS: Low
      levels of antigen-specific CD4 and CD8 T-cell responses (intracellular cytokine
      assay) were detected at 24 months (CD4-6/36 vaccine vs. 1/9 placebo; CD8-5/36
      vaccine vs. 0/9 placebo) of age. There was a nonsignificant trend toward higher
      cellular immune response rates in vaccine recipients compared with placebo. There
      were minimal binding antibody responses and no neutralizing antibodies detected.
      CONCLUSIONS: HIV-1-exposed infants are capable of generating low levels of
      cellular immune responses to ALVAC vaccine, similar to responses seen in adults.

PMID- 24091696
TI  - Emerging trends in CRF02_AG variants transmission among men who have sex with men
      in Spain.

PMID- 24091698
TI  - Time course and topographic distribution of ocular fundus pulsation measured by
      low-coherence tissue interferometry.
AB  - Low-coherence tissue interferometry is a technique for the depth-resolved
      measurement of ocular fundus pulsations. Whereas fundus pulsation amplitudes at
      preselected axial positions can readily be assessed by this method, coupling of
      the interferometer with a pulse oximeter additionally allows for the
      reconstruction of the time course of ocular fundus pulsation with respect to the
      cardiac cycle of the subject. For this purpose, the interferogram resulting from
      the superposition of waves reflected at the cornea and the ocular fundus is
      recorded synchronously with the plethysmogram. A new method for evaluating the
      time course of synthetic interferograms in combination with plethysmograms based
      on averaging several pulse periods has been developed. This technique allows for
      the analysis of amplitudes, time courses, and phase differences of fundus
      pulsations at preselected axial and transversal positions and for creating fundus
      pulsation movies. Measurements are performed in three healthy emmetropic subjects
      at angles from 0 deg to 18 deg to the axis of vision. Considerably different time
      courses, amplitudes, and phases with respect to the cardiac cycle are found at
      different angles. Data on ocular fundus pulsation obtained with this technique
      can--among other applications--be used to verify and to improve biomechanical
      models of the eye.

PMID- 24091697
TI  - The natural killer cell interferon-gamma response to bacteria is diminished in
      untreated HIV-1 infection and defects persist despite viral suppression.
AB  - OBJECTIVE: Natural killer (NK) cells are important in innate immune responses to
      bacterial and viral pathogens. HIV-1 infection is associated with opportunistic
      bacterial infections and with microbial translocation, but the nature of the NK
      cell response to bacteria during HIV-1 infection has not been studied
      extensively. The objective of this study was to compare NK cell responses to
      bacteria in HIV-1-infected versus that in uninfected individuals. METHODS:
      Multicolor flow cytometry was used to evaluate the ability of blood NK cell
      subsets (CD56CD16, CD56CD16, and CD56CD16) from treated, virally suppressed, and
      untreated viremic subjects with chronic HIV-1 infection and uninfected controls,
      to secrete interferon gamma (IFN-gamma) in response to the in vitro stimulation
      of peripheral blood mononuclear cells with heat-killed commensal Escherichia coli
      or pathogenic Salmonella typhimurium. RESULTS: All 3 NK cell subsets produced IFN
      gamma in response to bacteria, but CD56CD16 NK cells were least responsive.
      Untreated HIV-1-infected donors had increased frequencies of CD56CD16 NK cells
      and lower overall frequencies of IFN-gamma-producing NK cells responding to E.
      coli and S. typhimurium than did NK cells from uninfected donors. These NK cell
      defects were not fully restored in antiretroviral therapy-treated donors.
      Monocytes were necessary for NK cells to respond to bacteria, but the HIV
      associated defect was intrinsic to NK cells because the addition of normal
      monocytes did not restore IFN-gamma production in response to bacteria.
      CONCLUSIONS: Functional defects and numeric alterations of NK cell subsets lead
      to decreased frequencies of bacteria-reactive, IFN-gamma-producing NK cells in
      HIV-1-infected subjects, even those on antiretroviral therapy.

PMID- 24091699
TI  - Fitting and flailing: recognition of paediatric antiphospholipid syndrome.
AB  - Antiphospholipid syndrome (APS) is a systemic autoimmune condition where the
      presence of antiphospholipid antibodies is thought to predispose to thrombotic
      events. It is uncommon in the paediatric population, but current diagnostic
      criteria are based on adult population studies, making assessment of its true
      paediatric prevalence difficult. We present two cases of paediatric APS, who
      presented with primary neurological events, and discuss approaches to diagnosis,
      interpretation of screening investigations, including antinuclear antibodies
      (ANA), anti-extractable nuclear antigen (ENA) antibodies and lupus anticoagulant.
      Possible approaches to the management of paediatric APS are discussed. 

PMID- 24091700
TI  - Highly enantioselective iron(II)-catalyzed opening reaction of aromatic meso
      epoxides with indoles.
AB  - A highly enantioselective method for the catalytic cis-stilbene oxide opening
      reaction with indole derivatives was developed. The scope of the reaction was
      studied with a selection of aromatic meso-epoxides and various indoles, and the
      desired 2-(indol-3-yl)ethanol derivatives were obtained in good to excellent
      yields with excellent enantioselectivities (from 96 to >99% ee). 

PMID- 24091701
TI  - Formation of low density hydrous iron oxide via conformal transformation of MIL
      53(Fe).
AB  - Hydrous iron oxide materials with a predefined shape, photo-electrochemical
      activity, low density (estimated to be 0.32 g cm(-3)), and high fractal porosity
      (BET ca. 117 m(2) g(-1)) are formed via internal hydrolytic transformation of the
      crystalline metal-organic framework MIL-53(Fe) in dilute aqueous hydroxide. 

PMID- 24091702
TI  - Mitochondrial fusion directs cardiomyocyte differentiation via calcineurin and
      Notch signaling.
AB  - Mitochondrial morphology is crucial for tissue homeostasis, but its role in cell
      differentiation is unclear. We found that mitochondrial fusion was required for
      proper cardiomyocyte development. Ablation of mitochondrial fusion proteins
      Mitofusin 1 and 2 in the embryonic mouse heart, or gene-trapping of Mitofusin 2
      or Optic atrophy 1 in mouse embryonic stem cells (ESCs), arrested mouse heart
      development and impaired differentiation of ESCs into cardiomyocytes. Gene
      expression profiling revealed decreased levels of transcription factors
      transforming growth factor-beta/bone morphogenetic protein, serum response
      factor, GATA4, and myocyte enhancer factor 2, linked to increased Ca(2+)
      dependent calcineurin activity and Notch1 signaling that impaired ESC
      differentiation. Orchestration of cardiomyocyte differentiation by mitochondrial
      morphology reveals how mitochondria, Ca(2+), and calcineurin interact to regulate
      Notch1 signaling. 

PMID- 24091703
TI  - Changing social norm compliance with noninvasive brain stimulation.
AB  - All known human societies have maintained social order by enforcing compliance
      with social norms. The biological mechanisms underlying norm compliance are,
      however, hardly understood. We show that the right lateral prefrontal cortex
      (rLPFC) is involved in both voluntary and sanction-induced norm compliance. Both
      types of compliance could be changed by varying the neural excitability of this
      brain region with transcranial direct current stimulation, but they were affected
      in opposite ways, suggesting that the stimulated region plays a fundamentally
      different role in voluntary and sanction-based compliance. Brain stimulation had
      a particularly strong effect on compliance in the context of socially constituted
      sanctions, whereas it left beliefs about what the norm prescribes and about
      subjectively expected sanctions unaffected. Our findings suggest that rLPFC
      activity is a key biological prerequisite for an evolutionarily and socially
      important aspect of human behavior. 

PMID- 24091704
TI  - Measuring chromatin interaction dynamics on the second time scale at single-copy
      genes.
AB  - The chromatin immunoprecipitation (ChIP) assay is widely used to capture
      interactions between chromatin and regulatory proteins, but it is unknown how
      stable most native interactions are. Although live-cell imaging suggests short
      lived interactions at tandem gene arrays, current methods cannot measure rapid
      binding dynamics at single-copy genes. We show, by using a modified ChIP assay
      with subsecond temporal resolution, that the time dependence of formaldehyde
      cross-linking can be used to extract in vivo on and off rates for site-specific
      chromatin interactions varying over a ~100-fold dynamic range. By using the
      method, we show that a regulatory process can shift weakly bound TATA-binding
      protein to stable promoter interactions, thereby facilitating transcription
      complex formation. This assay provides an approach for systematic, quantitative
      analyses of chromatin binding dynamics in vivo. 

PMID- 24091705
TI  - Reading literary fiction improves theory of mind.
AB  - Understanding others' mental states is a crucial skill that enables the complex
      social relationships that characterize human societies. Yet little research has
      investigated what fosters this skill, which is known as Theory of Mind (ToM), in
      adults. We present five experiments showing that reading literary fiction led to
      better performance on tests of affective ToM (experiments 1 to 5) and cognitive
      ToM (experiments 4 and 5) compared with reading nonfiction (experiments 1),
      popular fiction (experiments 2 to 5), or nothing at all (experiments 2 and 5).
      Specifically, these results show that reading literary fiction temporarily
      enhances ToM. More broadly, they suggest that ToM may be influenced by engagement
      with works of art. 

PMID- 24091706
TI  - Entangling mechanical motion with microwave fields.
AB  - When two physical systems share the quantum property of entanglement,
      measurements of one system appear to determine the state of the other. This
      peculiar property is used in optical, atomic, and electrical systems in an effort
      to exceed classical bounds when processing information. We extended the domain of
      this quantum resource by entangling the motion of a macroscopic mechanical
      oscillator with a propagating electrical signal and by storing one half of the
      entangled state in the mechanical oscillator. This result demonstrates an
      essential requirement for using compact and low-loss micromechanical oscillators
      in a quantum processor, can be extended to sense forces beyond the standard
      quantum limit, and may enable tests of quantum theory. 

PMID- 24091707
TI  - Quantum limit of heat flow across a single electronic channel.
AB  - Quantum physics predicts that there is a fundamental maximum heat conductance
      across a single transport channel and that this thermal conductance quantum,
      G(Q), is universal, independent of the type of particles carrying the heat. Such
      universality, combined with the relationship between heat and information,
      signals a general limit on information transfer. We report on the quantitative
      measurement of the quantum-limited heat flow for Fermi particles across a single
      electronic channel, using noise thermometry. The demonstrated agreement with the
      predicted G(Q) establishes experimentally this basic building block of quantum
      thermal transport. The achieved accuracy of below 10% opens access to many
      experiments involving the quantum manipulation of heat.

PMID- 24091708
TI  - Investigations of g-factor for Ti3+, V4+ and Cr5+ in anatase.
AB  - The g-factor formulas for d(1) ions in anatase are deduced from the Jahn-Teller
      effect and contributions of the charge transfer levels. The tetragonal
      distortions R?-R? (where R? and R? denote the metal-ligand distances parallel
      with and perpendicular to the tetragonal axis) for Ti(3+), V(4+) and Cr(5+) in
      anatase are studied to calculate the g-factors and the calculations are in good
      agreement with the experimental values. The distortions are much larger than the
      corresponding values in the pure crystal. The contributions of the charge
      transfer levels to g factors increase with the increasing valence state. It must
      be taken into account in the precise calculations of g factors for the high
      valence state d(1) ions in crystals.

PMID- 24091709
TI  - The impact of smoking on thromboembolism and mortality in patients with incident
      atrial fibrillation: insights from the Danish Diet, Cancer, and Health study.
AB  - BACKGROUND: Smoking and atrial fibrillation (AF) are major health problems
      worldwide and are responsible for substantial health-care costs. Our aim was to
      investigate whether smoking impacts the risk of stroke and death in patients with
      AF. To test this hypothesis, we analyzed data from a large Danish cohort: the
      Diet, Cancer, and Health study. METHODS: This was a cohort study of 57,053 people
      (27,178 men; 29,876 women) aged 50 to 64 years. The risk of thromboembolism
      (ischemic stroke/arterial thromboembolism) or death according to smoking habits
      among 3,161 patients with incident AF (mean age, 66.9 years; 2,032 men, 1,129
      women) was assessed using Cox proportional hazard models after a median follow-up
      of 4.9 years. RESULTS: Of those with AF, 34% were current smokers and 37% former
      smokers. After adjustment for vitamin K antagonist treatment, the hazard ratios
      (HRs) (95% CI) of thromboembolism or death were 3.13 (1.72-6.37) and 2.73 (2.02
      3.70) among women and men who currently were heavy smokers (>25 g/d),
      respectively. The associations remained after adjustment for well-established
      risk factors with HRs of 3.64 (1.88-7.07) and 2.17 (1.59-2.95) among women and
      men, respectively. In a sensitivity analysis, smoking was still strongly
      associated with thromboembolism or death after censoring people with a cancer
      diagnosis during follow-up. CONCLUSIONS: Smoking is associated with a higher risk
      of thromboembolism or death in patients with AF even after adjusting for well
      recognized risk factors used in stroke risk stratification schemes. The
      associations may be modified by sex, as the associations were strongest among
      women.

PMID- 24091710
TI  - A tetraene aldehyde as the major sex pheromone component of the promethea moth
      (Callosamia promethea (Drury)).
AB  - The promethea moth Callosamia promethea is one of three species of silkmoths from
      the genus Callosamia that occur in North America. Cross attraction of males to
      heterospecific calling females has been observed in the field, and hybrid progeny
      have been produced by pairing heterospecifics in captivity. These observations
      suggest that all three species share or have considerable overlap in the sex
      attractant pheromones produced by females, so that other prezygotic isolating
      mechanisms, such as diel differences in reproductive activity, limit
      hybridization in the field. Coupled gas chromatography-electroantennogram
      detection and gas chromatography- mass-spectrometry analyses of extracts of
      volatiles collected from female promethea moths supported the identification of
      (4E,6E,11Z,13Z)-hexadeca-4,6,11,13-tetraenal [(4E,6E,11Z,13Z)-16:Ald] as the
      compound in extracts that elicited the largest responses from antennae of males.
      The identification was confirmed by non-selective synthesis of several isomers as
      analytical standards, and stereoselective synthesis of (4E,6E,11Z,13Z)-16:Ald for
      testing in field trials. Male moths were strongly attracted to synthetic
      (4E,6E,11Z,13Z)-16:Ald, suggesting that this compound is the major and possibly
      the only component of the sex pheromone of these large saturniid moths. Based on
      the cross-attraction of heterospecifics, it is likely that this is also a major
      pheromone component of the other two North American Callosamia species as well. 

PMID- 24091711
TI  - Prnp gene and cerebellum volume in patients with refractory mesial temporal lobe
      epilepsy.
AB  - The cellular prion protein, encoded by Prnp gene, is involved in neuroprotection,
      neuroplasticity and neurodevelopment. The variant allele Valine at codon 129 of
      the Prnp was associated with decreased brain volume in healthy volunteers and
      schizophrenic patients. We investigate the association between the cerebellum
      volume and the presence of variant allele Valine at codon 129 of the Prnp gene in
      patients with mesial temporal lobe epilepsy related to hippocampal sclerosis
      (MTLE-HS). The Prnp coding sequence was determined in 41 refractory MTLE-HS
      patients. The cerebellum volume corrected by the intracranial volume of patients
      with the normal Prnp genotypes was compared with that of patients presenting the
      variant alleles at codon 129. Twenty patients showed the Met129Met genotype, 16
      showed Met129Val, and 5 had Val129Val. There were no association among clinical,
      demographic, electrophysiological, antiepileptic drugs used, and the presence of
      the Prnp variant alleles. The presence of Prnp variant allele at codon 129 was
      not associated with the analyzed cerebellum volume. Prnp variant alleles at codon
      129 are not associated with cerebellum volume in patients with refractory MTLE
      HS.

PMID- 24091712
TI  - Twinkle mutations in two Chinese families with autosomal dominant progressive
      external ophthalmoplegia.
AB  - Autosomal dominant progressive external ophthalmoplegia (adPEO) is a common adult
      onset mitochondrial disease caused by mutations in nuclear DNA (nDNA). Twinkle is
      one of the nuclear genes associated with adPEO. Clinical, histochemical, and
      molecular genetics findings of 6 patients from two Chinese families with adPEO
      were reported. Two point mutations (c.1423G>C, p.A475P and c.1061G>C, p.R354P) of
      Twinkle gene have been found. Multiple mtDNA deletions were also detected in
      patient's muscle and fibroblasts. This study confirms two mutations in Chinese
      adPEO families, which were first reported in the Chinese population.

PMID- 24091713
TI  - Biomimicry and the culinary arts.
AB  - We present the results of a recent collaboration between scientists, engineers
      and chefs. Two particular devices are developed, both inspired by natural
      phenomena reliant on surface tension. The cocktail boat is a drink accessory, a
      self-propelled edible boat powered by alcohol-induced surface tension gradients,
      whose propulsion mechanism is analogous to that employed by a class of water
      walking insects. The floral pipette is a novel means of serving small volumes of
      fluid in an elegant fashion, an example of capillary origami modeled after a
      class of floating flowers. The biological inspiration and mechanics of these two
      devices are detailed, along with the process that led to their development and
      deployment. 

PMID- 24091714
TI  - Moving the solid phase: a platform technology for cartridge based sandwich
      immunoassays.
AB  - We report on a cartridge based platform for complex immunoassay formats that
      allows for flexible adaption of individual steps. It is a sample-to-answer system
      which is quantitative as well as sensitive. The target molecules are detected
      through a magnetic bead-based fluorescence sandwich immunoassay. The beads both
      constitute the solid phase for immobilizing capture molecules and are used for
      magnetic field activated incubation. The injection molded cartridge comprises
      several chambers separated by capillary valves. Chambers contain the assay
      reagents, through which the beads are manipulated via externally applied magnetic
      fields. Active incubation is made possible by assembling the beads into
      microstirrers and systematically scanning through a chamber. The beads are
      transported by focusing them to form an aggregate which subsequently is dragged
      through the valves. Once the aggregate enters a chamber, it is re-dispersed and
      magnetic actuation is used to re-assemble the beads into microstirrers. The assay
      protocol involves an incubation of sample with antibody coated magnetic beads,
      followed by steps for washing or separation, labeling with fluorescent detection
      antibody and finally fluorescence detection. An interleukin-8 assay served as a
      model for evaluating the system and a concentration as low as 5 pg/mL (0.625 pM)
      was successfully detected. The platform shows potential to be developed into a
      diagnostic tool to be used in a point-of-care testing (PoCT) environment.

PMID- 24091715
TI  - Topoisomerase 2beta: a promising molecular target for primary prevention of
      anthracycline-induced cardiotoxicity.
AB  - Anthracyclines are powerful chemotherapy agents that are still widely used today.
      However, their clinical use is limited by the development of dose-dependent
      cardiotoxicity. Recently, we showed that topoisomerase 2beta (Top2beta) is
      required for anthracycline to induce DNA double-strand breaks and changes in the
      transcriptome, leading to mitochondrial dysfunction and generation of reactive
      oxygen species. Furthermore, deleting Top2beta from cardiomyocytes prevented the
      development of anthracycline-induced cardiotoxicity in mice. On the basis of this
      molecular insight, new strategies should be developed to prevent anthracycline
      induced cardiotoxicity. First, Top2alpha-specific anthracyclines should be tested
      to determine whether they will spare the heart. Second, Top2beta should be
      studied as a potential biomarker to predict risk of developing cardiotoxicity
      before anthracycline treatment. Third, inhibiting and deleting Top2beta in the
      heart should also be tested as primary prevention strategies. We propose that
      Top2beta is a promising molecular target that can be used to design interventions
      to prevent anthracycline-induced cardiotoxicity.

PMID- 24091716
TI  - Current status of targeted therapy for anaplastic lymphoma kinase-rearranged non
      small cell lung cancer.
AB  - The identification of chromosomal rearrangements involving the anaplastic
      lymphoma kinase (ALK) gene in ~3-5% of non-small cell lung cancer (NSCLC) tissues
      and the demonstration that the first-in-class ALK tyrosine kinase inhibitor,
      crizotinib, can effectively target these tumors represent a significant advance
      in the evolution of personalized medicine for NSCLC. Single-arm studies
      demonstrating rapid and durable responses in the majority of ALK-positive NSCLC
      patients treated with crizotinib have been followed by a randomized phase III
      clinical trial in which superiority of crizotinib over chemotherapy was seen in
      previously treated ALK-positive NSCLC patients. However, despite the initial
      responses, most patients develop acquired resistance to crizotinib. Several novel
      therapeutic approaches targeting ALK-positive NSCLC are currently under
      evaluation in clinical trials, including second-generation ALK inhibitors, such
      as LDK378, CH5424802 (RO5424802802), and AP26113, and heat shock protein 90
      inhibitors.

PMID- 24091717
TI  - Performance of the Family Satisfaction with the End-of-Life Care (FAMCARE)
      measure in an ethnically diverse cohort: psychometric analyses using item
      response theory.
AB  - OBJECTIVE: The Family Satisfaction with End-of-Life Care (FAMCARE) has been used
      widely among caregivers to individuals with cancer. The aim of this study was to
      evaluate the psychometric properties of this measure using item response theory
      (IRT). METHODS: The analytic sample was comprised of caregivers to 1,983 patients
      with advanced cancer. Among the patients, 56 % were females, with mean age 59.9
      years (s.d. = 11.8), 20 % were non-Hispanic Black. The majority were family
      members either living with (44 %) or not living with (35 %) the patient. Factor
      analyses and IRT were used to examine the dimensionality, information, and
      reliability of the FAMCARE. RESULTS: Although a bi-factor model fit the data
      slightly better than did a unidimensional model, the loadings on the group
      factors were very low. Thus, a unidimensional model appears to provide adequate
      representation for the item set. The reliability estimates, calculated along the
      satisfaction (theta) continuum, were adequate (>0.80) for all levels of theta for
      which subjects had scores. Examination of the category response functions from
      IRT showed overlap in the lower categories with little unique information
      provided; moreover, the categories were not observed to be interval. Based on
      these analyses, a three-response category format was recommended: very satisfied,
      satisfied, and not satisfied. Most information was provided in the range
      indicative of either dissatisfaction or high satisfaction. CONCLUSIONS: These
      analyses support the use of fewer response categories and provide item parameters
      that form a basis for developing shorter-form scales. Such a revision has the
      potential to reduce respondent burden.

PMID- 24091718
TI  - Depression and family interaction among low-income, predominantly hispanic cancer
      patients: a longitudinal analysis.
AB  - PURPOSE: Among cancer patients, family interaction has been associated with
      depression. According to the stress generation theory, depression among cancer
      patients triggers stressful interpersonal events that contribute to poor family
      interactions and additional depression. This conflict may occur with a
      spouse/partner or other family member, including extended family. This study
      evaluated the longitudinal association between depression and marital and family
      conflict among low-income, predominantly Hispanic cancer patients. METHODS: Data
      were collected during a randomized controlled clinical trial of depression
      treatment among 472 low-income cancer patients with baseline depression scores of
      10 or more on the Patient Health Questionnaire-9 and whose depression symptoms
      and negative family interactions were assessed at baseline and at 6, 12, 18, and
      24 months. Considering that not all participants were in an intimate
      relationship, only 237 participants were included in the analysis of marital
      conflict. Mixed linear modeling with and without decomposition of between- and
      within-person variability was conducted to examine the longitudinal association
      between family interaction and depression. RESULTS: Overall, family conflict was
      significantly associated with changes in depression over time, and marital
      conflict was significantly associated with mean depression levels over 2 years.
      In addition, within-subject change in both marital and family conflict was
      significantly associated with within-patient deviation from average depression
      levels. CONCLUSIONS: Findings provide evidence of an association between
      depression and negative family interaction among depressed cancer patients.
      Cancer patients with clinically significant depressive symptoms may benefit from
      clinical assessment and psychotherapy relevant to family interaction.

PMID- 24091719
TI  - Chronicles of informal caregiving in cancer: using 'The Cancer Family Caregiving
      Experience' model as an explanatory framework.
AB  - BACKGROUND: Cancer caregiving has emerged as a dominant focus of research in
      recent years. A striking feature of this vast amount of literature is that it is
      static, examining certain points of the cancer trajectory, mostly the diagnosis
      and palliative care. Only The Cancer Caregiving Experience Model conceptualised
      the caregiving experience and explored the conceptual implications of cancer
      family caregiving research. AIM: The data from this paper aim to empirically
      support the Cancer Caregiving Experience model, by exploring the cancer
      caregiving experience longitudinally. METHODS: Semi-structured interviews with 53
      caregivers were carried out at patient's diagnosis (T1), 3 months (T2), 6 months
      (T3) and 12 months (T4) post diagnosis. RESULTS: Analysis of 139 interviews
      generated four themes that reflected a complex and dynamic process. The themes
      that mapped those of the model were "Primary stressors", "Secondary stressors",
      "Appraisal", "Cognitive-Behavioural responses" and "Health and Well Being".
      CONCLUSIONS: The study adds empirical support to The Cancer Caregiving Experience
      Model and confirms that different primary and secondary stressors influence how
      the caregivers perceive the caregiving demands, the coping mechanisms they employ
      and their health and well being during the cancer trajectory. Access to support
      services should be offered to all the caregivers from as early as the diagnosis
      period and take into account their specific needs.

PMID- 24091720
TI  - Prevalence of anxiety and depression and their risk factors in Chinese cancer
      patients.
AB  - PURPOSE: This paper aimed to obtain information on the levels of anxiety and
      depression among cancer patients in China. The factors influencing these
      psychological problems were also analyzed. METHODS: A total of 1,217 cancer
      patients were interviewed, and each participant was asked to complete a self
      administered questionnaire. The anxiety status, depression status, disease stage,
      tumor site, pain status, and performance status of the patients during the week
      prior to the interview were assessed. RESULTS: The anxiety and depression
      prevalence rates were 6.49 and 66.72 %, respectively. The prevalence rates of
      depression were 60.62 % for head and neck cancer, 77.19 % for lung cancer, 57.9 %
      for breast cancer, 75.81 % for esophagus cancer, 63.40 % for stomach cancer,
      68.42 % for liver cancer, 54.37 % for colorectal cancer, and 71.13 % for cervix
      cancer. The factors influencing depression of patients were performance status (P
      < 0.0001), pain (P = 0.0003), age (P < 0.0001), and education level (P < 0.0001).
      The risk factors of anxiety were performance status (P = 0.0007), age (P <
      0.0001), and gender (P < 0.0001). CONCLUSIONS: Depression was a more important
      psychological problem than anxiety in cancer patients. Compared with 3.8 % of the
      prevalence of depression in normal population, depression level was high among
      Chinese cancer patients. Patients with lung, esophagus, and cervix cancers were
      the high-risk groups for depression. Poor performance status, pain, old age, and
      low-level education were the predicting factors for depression.

PMID- 24091721
TI  - Gastrointestinal ostomies and sexual outcomes: a comparison of colorectal cancer
      patients by ostomy status.
AB  - PURPOSE: Research examining effects of ostomy use on sexual outcomes is limited.
      Patients with colorectal cancer were compared on sexual outcomes and body image
      based on ostomy status (never, past, and current ostomy). Differences in
      depression were also examined. METHODS: Patients were prospectively recruited
      during clinic visits and by tumor registry mailings. Patients with colorectal
      cancer (N = 141; 18 past ostomy; 25 current ostomy; and 98 no ostomy history)
      completed surveys assessing sexual outcomes (medical impact on sexual function,
      Female Sexual Function Index, International Index of Erectile Function), body
      image distress (Body Image Scale), and depressive symptoms (Center for
      Epidemiologic Studies Depression Scale-Short Form). Clinical information was
      obtained through patient validated self-report measures and medical records.
      RESULTS: Most participants reported sexual function in the dysfunctional range
      using established cut-off scores. In analyses adjusting for demographic and
      medical covariates and depression, significant group differences were found for
      ostomy status on impact on sexual function (p < .001), female sexual function (p
      = .01), and body image (p < .001). The current and past ostomy groups reported
      worse impact on sexual function than those who never had an ostomy (p < .001);
      similar differences were found for female sexual function. The current ostomy
      group reported worse body image distress than those who never had an ostomy (p <
      .001). No differences were found across the groups for depressive symptoms (p =
      .33) or male sexual or erectile function (p values >= .59). CONCLUSIONS:
      Colorectal cancer treatment puts patients at risk for sexual difficulties and
      some difficulties may be more pronounced for patients with ostomies as part of
      their treatment. Clinical information and support should be offered.

PMID- 24091722
TI  - Physical activity preferences of early-stage lung cancer survivors.
AB  - PURPOSE: Engagement in physical activity can provide important benefits for
      cancer patients and survivors, including those diagnosed with lung cancer.
      Despite this, many survivors do not engage in recommended levels of physical
      activity and little is known about the obstacles encountered by lung cancer
      survivors. The current study examines the physical activity preferences of early
      stage lung cancer survivors. METHOD: As part of a larger survey study, 175 non
      small cell lung cancer survivors who were on average 3.6 years from surgical
      treatment responded to questions regarding their preferences for physical
      activity and physical activity advice. Demographic and medical characteristics
      were also collected. RESULTS: The majority of respondents (62 %) reported a
      desire to receive advice regarding physical activity, predominantly before
      treatment (68 %), in face-to-face interactions (95 %) with a physician (80 %),
      and within the context of a cancer care center (92 %). Approximately half of
      participants indicated they would be interested in an exercise program tailored
      to lung cancer survivors and most individuals (73 %) reported feeling capable of
      engaging in an exercise program. Differences in physical activity preferences
      emerged based on demographic and disease characteristics. CONCLUSIONS: The
      majority of participants reported a desire for physical activity advice and a
      willingness to engage in physical activity. Important differences were found
      based on demographic and medical characteristics, which may warrant consideration
      in the development and dissemination of physical activity interventions for this
      cancer survivor population.

PMID- 24091723
TI  - Assessment of Traub formula and ketone bodies in cause of death investigations.
AB  - Diabetes and alcohol abuse may cause severe metabolic disturbances that can be
      fatal. These may be difficult to diagnose in autopsies based solely on
      macroscopical and histological findings. In such cases, metabolic markers, such
      as postmortem glucose and ketone levels, can provide supporting information.
      Glucose or combined glucose and lactate, the Traub value, is often used to
      indicate hyperglycemia. The use of the Traub value, however, has been questioned
      by some, because the lactate levels are known to elevate in postmortem samples
      also due to other reasons than glycolysis of glucose molecules. Ketoacidosis can
      be detected by analyzing ketone body levels, especially beta-hydroxybutyric acid
      (BHB). Acetone is also elevated in severe cases of ketoacidosis. Here, we have
      evaluated the value of these biomarkers for postmortem determination of the
      metabolic disturbances. Retrospective data of 980 medico-legal autopsies
      performed in Finland, where glucose, lactate and ketone bodies were analyzed, was
      collected. Our findings show that the Traub value indicates hyperglycemia, even
      when glucose levels are low. For diagnosis, evaluation of complementing markers,
      e.g. ketone bodies and glycated hemoglobin is needed. Our results show that BHB
      can be used for screening and diagnosis of ketoacidosis. Acetone alone is not
      sufficient, since it is elevated only in the most severe cases. We also found
      that alcohol abuse rarely causes severe ketoacidosis. However, sporadic cases do
      exist where ketone body levels are extremely high. Despite this, alcoholic
      ketoacidosis is very rarely diagnosed as the cause of death. 

PMID- 24091724
TI  - Is asthma an infectious disease? New evidence.
AB  - The pathogenetic mechanisms leading to asthma are likely to be diverse,
      influenced by multiple genetic polymorphisms as well as elements of the
      environment. Recent data on the microbiome of the airway have revealed intriguing
      differences between the number and diversity of microbial populations in healthy
      persons and asthmatics. There is convincing evidence that early viral infections,
      particularly with human rhinovirus and respiratory syncytial virus, are often
      associated with the development of chronic asthma and with exacerbations. Recent
      studies suggest that two unrelated types of atypical bacteria, Mycoplasma
      pneumoniae (Mpn) and Chlamydia pneumoniae, are present in the airways of a
      substantial proportion of the population, bringing up the possibility that the
      persistent presence of the organism may contribute to the asthmatic phenotype in
      a subset of patients. This review will examine the current data regarding a
      possible role for infection in chronic asthma with a particular focus on atypical
      bacterial infections. 

PMID- 24091725
TI  - A new class of animal collagen masquerading as an insect silk.
AB  - Collagen is ubiquitous throughout the animal kingdom, where it comprises some 28
      diverse molecules that form the extracellular matrix within organisms. In the
      1960s, an extracorporeal animal collagen that forms the cocoon of a small group
      of hymenopteran insects was postulated. Here we categorically demonstrate that
      the larvae of a sawfly species produce silk from three small collagen proteins.
      The native proteins do not contain hydroxyproline, a post translational
      modification normally considered characteristic of animal collagens. The function
      of the proteins as silks explains their unusual collagen features. Recombinant
      proteins could be produced in standard bacterial expression systems and assembled
      into stable collagen molecules, opening the door to manufacture a new class of
      artificial collagen materials. 

PMID- 24091726
TI  - Deficiency in PER proteins has no effect on the rate of spontaneous and radiation
      induced carcinogenesis.
AB  - There is a growing body of evidence that components of the circadian clock are
      involved in modulation of numerous signaling pathways, and that clock
      deregulation due to environmental or genetic factors contributes to the
      development of various pathologies, including cancer. Previous work performed in
      tissue culture and in in vivo mouse models defined mammalian PERIOD proteins as
      tumor suppressors, although some experimental inconsistencies (the use of mice on
      mixed genetic background, lack of sexual discrimination) did not allow a
      definitive conclusion. To address this issue in a systematic way, we performed a
      detailed analysis comparing the incidence of tumor development after low-dose
      ionizing radiation in male and female wild-type, Per1(-/-), and Per2(-/-) mice.
      We showed that in contrast to previous reports deficiency in either Per1 or Per2
      genes by itself does not make mice more tumor-prone; moreover, some of the long
      term effects of ionizing radiation in Per2-deficient mice are reminiscent more of
      accelerated aging rather than tumor-prone phenotype. Our histopathological
      analysis also revealed significant sexual dimorphism both in the rate of
      radiation-induced tumorigenesis and in the spectrum of tumors developed, which
      underscores the importance of using sex-matched experimental groups for in vivo
      studies. Based on our results, we suggest that the role of PER proteins as bona
      fide tumor suppressors needs to be reevaluated. 

PMID- 24091727
TI  - Mitotic perturbations induced by Nek2 overexpression require interaction with
      TRF1 in breast cancer cells.
AB  - NIMA-related kinase 2 (Nek2), a serine-threonine protein kinase, plays a major
      role in mitotic progression, including timing of mitotic entry, chromatin
      condensation, spindle organization, and cytokinesis. Nek2 overexpression results
      in premature centrosome separation, while kinase death Nek2 mutant expression or
      Nek2-depleted cells lead to centrosome separation failure. In addition, it has
      been revealed that telomeric repeat binding factor 1 (TRF1) interacts directly
      with Nek2. TRF1 not only regulates telomere length, but is also associated with
      cell cycle regulation. However, the interactions and correlations between Nek2
      and TRF1 are far from clear. Here, we show that mitotic aberrations through Nek2
      overexpression are likely to require TRF1. Our results demonstrate that Nek2
      directly binds and phosphorylates TRF1 through multiple sites on TRF1. Nek2
      overexpression in breast cancer cells, MDA-MB-231 and MCF7, results in increased
      numbers of centrosomes and multinucleated cells, which leads to cytokinetic
      failure and aneuploidization. Additionally, TRF1 depletion by siRNA prevents the
      phenomenon of unaligned chromosomes by Nek2 overexpression during metaphase.
      Concurrent Nek2 overexpression and TRF1-depleted cells demonstrated <= 2
      centrosomes per cell, similar to mock plasmid and negative control siRNA
      transfected cells. Interestingly, when exogenous TRF1 was added back in Nek2
      overexpressed cells with endogenous TRF1 depletion, cells had re-induced
      cytokinetic failure. Therefore, we propose that TRF1 is required for
      overexpressed Nek2 to trigger abnormal mitosis and chromosomal instability. 

PMID- 24091728
TI  - Phosphorylation of eIF4GII and 4E-BP1 in response to nocodazole treatment: a
      reappraisal of translation initiation during mitosis.
AB  - Translation mechanisms at different stages of the cell cycle have been studied
      for many years, resulting in the dogma that translation rates are slowed during
      mitosis, with cap-independent translation mechanisms favored to give expression
      of key regulatory proteins. However, such cell culture studies involve
      synchronization using harsh methods, which may in themselves stress cells and
      affect protein synthesis rates. One such commonly used chemical is the
      microtubule de-polymerization agent, nocodazole, which arrests cells in mitosis
      and has been used to demonstrate that translation rates are strongly reduced
      (down to 30% of that of asynchronous cells). Using synchronized HeLa cells
      released from a double thymidine block (G 1/S boundary) or the Cdk1 inhibitor,
      RO3306 (G 2/M boundary), we have systematically re-addressed this dogma. Using
      FACS analysis and pulse labeling of proteins with labeled methionine, we now show
      that translation rates do not slow as cells enter mitosis. This study is
      complemented by studies employing confocal microscopy, which show enrichment of
      translation initiation factors at the microtubule organizing centers, mitotic
      spindle, and midbody structure during the final steps of cytokinesis, suggesting
      that translation is maintained during mitosis. Furthermore, we show that
      inhibition of translation in response to extended times of exposure to nocodazole
      reflects increased eIF2alpha phosphorylation, disaggregation of polysomes, and
      hyperphosphorylation of selected initiation factors, including novel Cdk1
      dependent N-terminal phosphorylation of eIF4GII. Our work suggests that effects
      on translation in nocodazole-arrested cells might be related to those of the
      treatment used to synchronize cells rather than cell cycle status. 

PMID- 24091730
TI  - A non-redundant function of cyclin E1 in hematopoietic stem cells.
AB  - A precise balance between quiescence and proliferation is crucial for the
      lifelong function of hematopoietic stem cells (HSCs). Cyclins E1 and E2 regulate
      exit from quiescence in fibroblasts, but their role in HSCs remains unknown.
      Here, we report a non-redundant role for cyclin E1 in mouse HSCs. A long-term
      culture-initiating cell (LTC-IC) assay indicated that the loss of cyclin E1, but
      not E2, compromised the colony-forming activity of primitive hematopoietic
      progenitors. Ccne1(-/-) mice showed normal hematopoiesis in vivo under
      homeostatic conditions but a severe impairment following myeloablative stress
      induced by 5-fluorouracil (5-FU). Under these conditions, Ccne1(-/-) HSCs were
      less efficient in entering the cell cycle, resulting in decreased hematopoiesis
      and reduced survival of mutant mice upon weekly 5-FU treatment. The role of
      cyclin E1 in homeostatic conditions became apparent in aged mice, where HSC
      quiescence was increased in Ccne1(-/-) animals. On the other hand, loss of cyclin
      E1 provided HSCs with a competitive advantage in bone marrow serial
      transplantation assays, suggesting that a partial impairment of cell cycle entry
      may exert a protective role by preventing premature depletion of the HSC
      compartment. Our data support a role for cyclin E1 in controlling the exit from
      quiescence in HSCs. This activity, depending on the physiological context, can
      either jeopardize or protect the maintenance of hematopoiesis. 

PMID- 24091729
TI  - miR-29b induces SOCS-1 expression by promoter demethylation and negatively
      regulates migration of multiple myeloma and endothelial cells.
AB  - Epigenetic silencing of tumor suppressor genes frequently occurs and may account
      for their inactivation in cancer cells. We previously demonstrated that miR-29b
      is a tumor suppressor microRNA (miRNA) that targets de novo DNA
      methyltransferases and reduces the global DNA methylation of multiple myeloma
      (MM) cells. Here, we provide evidence that epigenetic activity of miR-29b leads
      to promoter demethylation of suppressor of cytokine signaling-1 (SOCS-1), a
      hypermethylated tumor suppressor gene. Enforced expression of synthetic miR-29b
      mimics in MM cell lines resulted in SOCS-1 gene promoter demethylation, as
      assessed by Sequenom MassARRAY EpiTYPER analysis, and SOCS-1 protein
      upregulation. miR-29b-induced SOCS-1 demethylation was associated with reduced
      STAT3 phosphorylation and impaired NFkappaB activity. Downregulation of VEGF-A
      and IL-8 mRNAs could be detected in MM cells transfected with miR-29b mimics as
      well as in endothelial (HUVEC) or stromal (HS-5) cells treated with conditioned
      medium from miR-29b-transfected MM cells. Notably, enforced expression of miR-29b
      mimics increased adhesion of MM cells to HS-5 and reduced migration of both MM
      and HUVEC cells. These findings suggest that miR-29b is a negative regulator of
      either MM or endothelial cell migration. Finally, the proteasome inhibitor
      bortezomib, which induces the expression of miR-29b, decreased global DNA
      methylation by a miR-29b-dependent mechanism and induced SOCS-1 promoter
      demethylation and protein upregulation. In conclusion, our data indicate that miR
      29b is endowed with epigenetic activity and mediates previously unknown functions
      of bortezomib in MM cells. 

PMID- 24091731
TI  - Differences in 53BP1 and BRCA1 regulation between cycling and non-cycling cells.
AB  - BRCA1 and 53BP1 play decisive roles in the choice of DNA double-strand break
      repair mechanisms. BRCA1 promotes DNA end resection and homologous recombination
      (HR) during S/G 2 phases of the cell cycle, while 53BP1 inhibits end resection
      and facilitates non-homologous end-joining (NHEJ), primarily during G 1. This
      competitive relationship is critical for genome integrity during cell division.
      However, their relationship in the many cells in our body that are not cycling is
      unknown. We discovered profound differences in 53BP1 and BRCA1 regulation between
      cycling and non-cycling cells. Cellular growth arrest results in transcriptional
      downregulation of BRCA1 and activation of cathepsin-L (CTSL)-mediated degradation
      of 53BP1. Accordingly, growth-arrested cells do not form BRCA1 or 53BP1 ionizing
      radiation-induced foci (IRIF). Interestingly, cell cycle re-entry reverts this
      scenario, with upregulation of BRCA1, downregulation of CTSL, stabilization of
      53BP1, and 53BP1 IRIF formation throughout the cycle, indicating that BRCA1 and
      53BP1 are important in replicating cells and dispensable in non-cycling cells. We
      show that CTSL-mediated degradation of 53BP1, previously associated with
      aggressive breast cancers, is an endogenous mechanism of non-cycling cells to
      balance NHEJ (53BP1) and HR (BRCA1). Breast cancer cells exploit this mechanism
      to ensure genome stability and viability, providing an opportunity for targeted
      therapy. 

PMID- 24091732
TI  - Single cell heterogeneity: why unstable genomes are incompatible with average
      profiles.
AB  - Multi-level heterogeneity is a fundamental but underappreciated feature of
      cancer. Most technical and analytical methods either completely ignore
      heterogeneity or do not fully account for it, as heterogeneity has been
      considered noise that needs to be eliminated. We have used single-cell and
      population-based assays to describe an instability-mediated mechanism where
      genome heterogeneity drastically affects cell growth and cannot be accurately
      measured using conventional averages. First, we show that most unstable cancer
      cell populations exhibit high levels of karyotype heterogeneity, where it is
      difficult, if not impossible, to karyotypically clone cells. Second, by comparing
      stable and unstable cell populations, we show that instability-mediated karyotype
      heterogeneity leads to growth heterogeneity, where outliers dominantly contribute
      to population growth and exhibit shorter cell cycles. Predictability of
      population growth is more difficult for heterogeneous cell populations than for
      homogenous cell populations. Since "outliers" play an important role in cancer
      evolution, where genome instability is the key feature, averaging methods used to
      characterize cell populations are misleading. Variances quantify heterogeneity;
      means (averages) smooth heterogeneity, invariably hiding it. Cell populations of
      pathological conditions with high genome instability, like cancer, behave
      differently than karyotypically homogeneous cell populations. Single-cell
      analysis is thus needed when cells are not genomically identical. Despite
      increased attention given to single-cell variation mediated heterogeneity of
      cancer cells, continued use of average-based methods is not only inaccurate but
      deceptive, as the "average" cancer cell clearly does not exist. Genome-level
      heterogeneity also may explain population heterogeneity, drug resistance, and
      cancer evolution. 

PMID- 24091733
TI  - The correlation between global health experiences in low-income countries on
      choice of primary care residencies for graduates of an urban US medical school.
AB  - This study sought to determine whether medical students who participate in a
      global health elective in a low-income country select residencies in primary care
      at higher rates compared with their classmates and US medical graduates in
      general. Given the projected increase in demand for primary care physicians,
      particularly in underserved areas, understanding possible factors that encourage
      training in primary care or enhance interest in the care of underserved
      populations may identify opportunities in medical school training. The authors
      used data from the Office of Student Affairs, SUNY Downstate College of Medicine
      and the National Residency Matching Program to compare rates of primary care
      residency selection from 2004 to 2012. Residency selections for students who
      participated in the SUNY Downstate School of Public Health Global Health Elective
      were compared with those of their classmates and with residency match data for US
      seniors. In 7 of the 8 years reviewed, students who participated in the SUNY
      Downstate School of Public Health Global Health Elective selected primary care
      residencies at rates higher than their classmates. Across years, 57% of the
      students who completed the elective matched to primary care residences, which was
      significantly higher than the 44% for the remainder of Downstate's medical
      student class (p = 0.0023). In 6 of the 8 years, Downstate students who
      participated in the Global Health Elective selected primary care residencies at
      rates higher than US medical school seniors in general; rates were the same for
      both Downstate Global Health Elective students and US medical school seniors in
      2009. Students who participated in a global health experience in a low-income
      country selected primary care residencies at higher rates than their classmates
      and US medical school graduates in general. Understanding how these experiences
      correlate with residency selection requires further investigation; areas of
      future study are discussed.

PMID- 24091734
TI  - Comparison of an HPTLC method with the Reflectoquant assay for rapid
      determination of 5-hydroxymethylfurfural in honey.
AB  - 5-Hydroxymethylfurfural (HMF) was analyzed in 17 botanical varieties of honey
      from 12 countries. A recently developed high-performance thin-layer
      chromatographic (HPTLC) method was limited because of increased matrix effects at
      higher honey sample loading. Therefore, the method was modified to achieve higher
      sensitivity and eliminate matrix interference by use of rectangular application
      combined with a focusing step. The HPTLC results were compared with results from
      the new spectrophotometric Reflectoquant hydroxymethylfurfural assay. Both
      methods had quantification limits of 4 mg kg(-1) and were suitable for rapid
      quantification of HMF in honey at the strictest regulated level of 15 mg kg(-1).
      Comparable results were obtained for the 17 honey samples, with a mean deviation
      of 2.9 mg kg(-1) (15%). The optimized HPTLC method was proved to be highly matrix
      robust and was validated for the 17 different honey matrices (correlation
      coefficients >=0.9994 (n = 6), mean intra-day precision 3.2% (n = 3 within a
      plate; n = 2 repeated within a day), mean inter-day precision 3.7% (n = 3), mean
      reproducibility over the whole procedure including sample preparation 4.1% (n =
      2), and mean recovery 106.9% (n = 5 different concentrations; n = 4 different
      honey matrices). Recovery for a range of different application volumes, and thus
      for different honey matrix loading, differed by only <=4.2%. HMF results when
      calculated by use of external calibration and by use of the standard addition
      method varied by 8.8%. Both revealed that any matrix effect was minor and that
      the original matrix interference problem was successfully solved.

PMID- 24091735
TI  - The use of trimethylsilyl cyanide derivatization for robust and broad-spectrum
      high-throughput gas chromatography-mass spectrometry based metabolomics.
AB  - Reproducible and quantitative gas chromatography-mass spectrometry (GC-MS)-based
      metabolomics analysis of complex biological mixtures requires robust and broad
      spectrum derivatization. We have evaluated derivatization of complex metabolite
      mixtures using trimethylsilyl cyanide (TMSCN) and the most commonly used
      silylation reagent N-methyl-N-(trimethylsilyl)trifluoroacetamide (MSTFA). For the
      comparative analysis, two metabolite mixtures, a standard complex mixture of 35
      metabolites covering a range of amino acids, carbohydrates, small organic acids,
      phenolic acids, flavonoids and triterpenoids, and a phenolic extract of blueberry
      fruits were used. Four different derivatization methods, (1) direct silylation
      using TMSCN, (2) methoximation followed by TMSCN (M-TMSCN), (3) direct silylation
      using MSTFA, and (4) methoximation followed by MSTFA (M-MSTFA) were compared in
      terms of method sensitivity, repeatability, and derivatization reaction time. The
      derivatization methods were observed at 13 different derivatization times, 5 min
      to 60 h, for both metabolite mixtures. Fully automated sample derivatization and
      injection enabled excellent repeatability and precise method comparisons. At the
      optimal silylation times, peak intensities of 34 out of 35 metabolites of the
      standard mixture were up to five times higher using M-TMSCN compared with M
      MSTFA. For direct silylation of the complex standard mixture, the TMSCN method
      was up to 54 times more sensitive than MSTFA. Similarly, all the metabolites
      detected from the blueberry extract showed up to 8.8 times higher intensities
      when derivatized using TMSCN than with MSTFA. Moreover, TMSCN-based silylation
      showed fewer artifact peaks, robust profiles, and higher reaction speed as
      compared with MSTFA. A method repeatability test revealed the following
      robustness of the four methods: TMSCN > M-TMSCN > M-MSTFA > MSTFA.

PMID- 24091736
TI  - A novel approach to quantitative LC-MS/MS: therapeutic drug monitoring of
      clozapine and norclozapine using isotopic internal calibration.
AB  - Therapeutic drug monitoring (TDM) requires timely results in order to be
      clinically helpful. Such assays, when carried out using mass spectrometry-based
      methods, typically involve a batched sample approach with multipoint calibration.
      Isotopic internal calibration offers the possibility of open-access mass
      spectrometric analysis with consequent shortening of turnaround times. We
      measured plasma clozapine and N-desmethylclozapine (norclozapine) concentrations
      in (1) external quality assessment (EQA) samples (N = 22) and (2) patient samples
      (N = 100) using liquid chromatography-tandem mass spectrometry with isotopic
      internal calibration (ICAL-LC-MS/MS). Analyte concentrations were calculated from
      graphs of the response of three internal calibrators (clozapine-D4, norclozapine
      D8, and clozapine-D8) against concentration. Precision (% RSD) and accuracy (%
      nominal concentrations) for the ICAL-LC-MS/MS method were <5 % and 104-112 %,
      respectively for both analytes. There was excellent agreement with consensus mean
      and with 'spiked' values on analysis of the EQA samples (R (2) = 0.98 and 0.97,
      respectively, inclusive of clozapine and norclozapine results). In the patient
      samples, comparison against traditionally calibrated HPLC-UV and LC-MS/MS methods
      showed excellent agreement (R (2) = 0.97 or better) with small albeit significant
      mean differences (<0.041 and <0.042 mg/L for clozapine and norclozapine,
      respectively). These differences probably reflect discrepancies in the in-house
      preparation of calibrators and/or interference in the UV method. Internal
      calibration offers a novel and attractive alternative to traditionally calibrated
      batch analysis in analytical toxicology. The method described has been validated
      for use in the high-throughput TDM of clozapine and norclozapine, and allows for
      (1) same-day reporting of results and (2) significant cost savings.

PMID- 24091737
TI  - Direct observation of bulk and surface chemical morphologies of Ginkgo biloba
      leaves by Fourier transform mid- and near-infrared microspectroscopic imaging.
AB  - Fourier transform infrared microspectroscopy is a powerful tool to obtain
      knowledge about the spatial and/or temporal distributions of the chemical
      compositions of plants for better understanding of their biological properties.
      However, the chemical morphologies of plant leaves in the plane of the blade are
      barely studied, because sections in this plane for mid-infrared transmission
      measurements are difficult to obtain. Besides, native compositions may be changed
      by chemical reagents used when plant samples are microtomed. To improve methods
      for direct infrared microspectroscopic imaging of plant leaves in the plane of
      the blade, the bulk and surface chemical morphologies of nonmicrotomed Ginkgo
      biloba leaves were characterized by near-infrared transmission and mid-infrared
      attenuated total reflection microspectroscopic imaging. A new self-modeling curve
      resolution procedure was proposed to extract the spectral and concentration
      information of pure compounds. Primary and secondary metabolites of secretory
      cavities, veins, and mesophylls of Ginkgo biloba leaf blades were analyzed, and
      the distributions of cuticle, protein, calcium oxalate, cellulose, and ginkgolic
      acids on the adaxial surface were determined. By the integration of multiple
      infrared microspectroscopic imaging and chemometrics methods, it is possible to
      analyze nonmicrotomed leaves and other plant samples directly to understand their
      native chemical morphologies in detail. 

PMID- 24091738
TI  - Separation and characterization of natural and synthetic macromolecules.

PMID- 24091739
TI  - Pressurised hot water extraction in continuous flow mode for thermolabile
      compounds: extraction of polyphenols in red onions.
AB  - Extraction and analysis of labile compounds in complex sample matrices, such as
      plants, is often a big analytical challenge. In this work, the use of a "green
      and clean" pressurised hot water extraction (PHWE) approach performed in
      continuous flow mode is explored. Experimental data for extraction and
      degradation kinetics of selected compounds were utilised to develop a continuous
      flow extraction (CFE) method targeting thermolabile polyphenols in red onions,
      with detection by high-performance liquid chromatography (HPLC)-diode array
      detection (DAD)-mass spectrometry (MS). Water containing ethanol and formic acid
      was used as extraction solvent. Method performance was focused on extraction
      yield with minimal analyte degradation. By adjusting the flow rate of the
      extraction solvent, degradation effects were minimised, and complete extraction
      could be achieved within 60 min. The CFE extraction yields of the polyphenols
      investigated were 80-90 % of the theoretically calculated quantitative yields and
      were significantly higher than the yields obtained by conventional methanol
      extraction and static batch extraction (70-79 and 58-67 % of the theoretical
      yields, respectively). The precision of the developed method was lower than 8 %
      expressed as relative standard deviation. 

PMID- 24091740
TI  - The determination of pharmaceutical residues in cooked and uncooked marine
      bivalves using pressurised liquid extraction, solid-phase extraction and liquid
      chromatography-tandem mass spectrometry.
AB  - An optimised and validated method for the determination of pharmaceutical
      residues in blue mussels (Mytilus spp.) is presented herein, as well as an
      investigation of the effect of cooking (by steaming) on any potential difference
      in human exposure risk. Selected pharmaceuticals included two non-steroidal anti
      inflammatory drugs (diclofenac and mefenamic acid), an antibiotic (trimethoprim),
      an anti-epileptic (carbamazepine) and a lipid regulator (gemfibrozil). An in vivo
      exposure experiment was set up in the laboratory in which mussels were exposed
      either directly by injection (10 ng) or daily through spiked artificial seawater
      (ASW) over 96 h. In liquid matrices, pharmaceutical residues were either
      determined using liquid chromatography-tandem mass spectrometry (LC-MS/MS)
      directly, or in combination with solid-phase extraction (SPE) for analyte
      concentration purposes. The extraction of pharmaceuticals from mussel tissues
      used an additional pressurised liquid extraction step prior to SPE and LC-MS/MS.
      Limits of quantification of between 2 and 46 ng L(-1) were achieved for extracted
      cooking water and ASW, between 2 and 64 MUg L(-1) for ASW in exposure tanks, and
      between 4 and 29 ng g(-1) for mussel tissue. Method linearities were achieved for
      pharmaceuticals in each matrix with correlation coefficients of R (2) > 0.975. A
      selection of exposed mussels was also cooked (via steaming) and analysed using
      the optimised method to observe any effect on detectable concentrations of parent
      pharmaceuticals present. An overall increase in pharmaceutical residues in the
      contaminated mussel tissue and cooking water was observed after cooking.

PMID- 24091741
TI  - Proteome investigation of the non-model plant pomegranate (Punica granatum L.).
AB  - A gel-free, shotgun proteomics approach was used to characterize pomegranate aril
      proteome by nanoliquid chromatography-high-resolution tandem mass spectrometry.
      To identify both high-abundance and low-abundance proteins, we applied two
      distinct sample preparation protocols, i.e., a classical one widely applied in
      literature and a second one able to reduce the dynamic range of protein
      concentration of the sample, based on combinatorial hexapeptide ligand library
      technology. However, the proteins identified with the latter protocol were only a
      small minority. Because pomegranate is a non-model plant species, i.e.,
      information of its genome sequence are lacking, only a few protein sequences are
      included in the most widely known protein sequence databases. To improve both the
      number of identified proteins and data reliability, identification was performed
      integrating the results obtained with three distinct plant protein databases,
      since the majority of proteins could only be attributed by homology with other
      plant species. Nevertheless, many proteins had assigned only one unique peptide,
      because of the phylogenetic distance of pomegranate from the main model plants.
      After manual revision of the identified proteins to eliminate the redundant or
      ambiguous identifications, a list of 1,488 proteins was obtained, only six of
      which belonging to pomegranate species. To the author's best knowledge, this is
      the first work aimed at the proteomic characterization of Punica granatum. 

PMID- 24091742
TI  - Structural investigation of ionic liquid/rubrene single crystal interfaces by
      using frequency-modulation atomic force microscopy.
AB  - Frequency-modulation atomic force microscopy (FM-AFM) was employed to reveal the
      structural properties of a rubrene single crystal immersed in an ionic liquid. We
      found large vacancies formed by the anisotropic dissolution of rubrene molecules.
      Molecular resolution imaging revealed that structures of FM-AFM images deviated
      from the bulk-terminated structure. 

PMID- 24091743
TI  - Prognostic value of tumor-infiltrating mast cells in outcome of patients with
      esophagus squamous cell carcinoma.
AB  - BACKGROUND: Squamous cell carcinoma (SCC) of the esophagus is one of the most
      common malignancies of the gastrointestinal tract and carries poor prognosis. The
      role of mast cell density (MCD) in the prognosis of most human tumors is partly
      known, and there is a growing body of studies addressing it. However, the
      prognostic value of MCD has not been investigated in esophageal SCC, and thus, it
      was the subject during this study. METHODS: In this study, 78 patients with
      esophageal SCC in pT = 3 were selected, their MCD was evaluated with toluidine
      blue staining, and the relationship with survival rate was analyzed. Patients
      were compared in identical groups of lymph node involvement and post-surgery
      complementary therapy. RESULTS: Survival rate was significantly decreased in
      patients with high MCD based on Kaplan-Meier analysis (P < 0.001). This
      relationship was also found in groups with similar lymph node involvement and
      post-surgery therapies. CONCLUSIONS: The results of the current study showed that
      high MCD in the invasive edge of tumor is related to tumor progression and
      decreased survival rate following surgery.

PMID- 24091745
TI  - Genetic diversity of fluoroquinolone-nonsusceptible Streptococcus pneumoniae
      clinical isolates and the first identification of serotype 20B in China.
AB  - The purpose of this study was to investigate the genetic characteristics of
      fluoroquinolone-nonsusceptible Streptococcus pneumoniae clinical isolates in
      China. A total of 377 S. pneumoniae clinical isolates, including 307 pediatric
      strains and 70 adult strains, were collected from eight centers in China. The
      minimal inhibitory concentrations (MICs) of 10 antimicrobial agents were
      determined by agar dilution. Multilocus sequence typing (MLST), serotyping, and
      quinolone resistance-determining region (QRDR) variations were conducted in
      levofloxacin-nonsusceptible isolates by polymerase chain reaction (PCR)-based
      methods. Seven levofloxacin-nonsusceptible isolates were found, with an overall
      resistance rate of 1.9 % (7/377) and 8.6 % (6/70) in adults. Sequence analyses of
      parC, gyrA, and parE QRDRs in levofloxacin-resistant isolates demonstrated
      mutations in dual target sites at the hot spots. These seven strains represented
      multiple clones: two strains were serotype 19F (Taiwan(19F)-14) and MLST clonal
      complex (CC) 271/320, two were typed as 23F (Spain(23F)-1) and CC81, two were
      determined as serotype 20B and a new sequence type of ST6935, and one non
      serotypeable pediatric strain belonged to a new sequence type of ST6946. Two
      serotype 19F strains possessed a variety of characteristic alterations of
      viridans group streptococci in gyrA (Ser114Gly) or parC (Ser52Gly, Asn91Asp).
      Fluoroquinolone-nonsusceptible S. pneumoniae isolates showed a substantial degree
      of genetic diversity and belonged to pre-existing epidemic clones together with
      native clones. S. pneumoniae strains with serotype 20B was recovered for the
      first time to be associated with levofloxacin resistance in China.

PMID- 24091746
TI  - The healthcare and societal burden associated with influenza in vaccinated and
      unvaccinated European and Israeli children.
AB  - Few data exist regarding the healthcare and societal burden of culture-confirmed
      influenza illness in European and Israeli children. The current analysis
      describes this burden in vaccinated and unvaccinated children 2-17 years of age.
      Healthcare and societal burden outcomes were prospectively collected for culture
      confirmed influenza illness in three previous randomized studies: a study of live
      attenuated influenza vaccine (LAIV) versus placebo in children aged <48 months
      attending day care (N = 846-973), and studies of LAIV versus inactivated
      influenza vaccine (IIV) in children aged <72 months with recurrent respiratory
      infections (N = 1,609) and in children aged 6-17 years with asthma (N = 2,211).
      The incidence of each endpoint among enrolled subjects and subjects with
      influenza was determined by treatment group and by country. Among subjects with
      influenza, 57-91% missed school or day care, 45-90% used non-antibiotic
      medications, 29-55% of parents missed work, 17-55% used antibiotics, 11-62% had
      additional provider visits, and 9-20% had acute otitis media. Where evaluated,
      rates of outcomes were generally similar between countries. Among all children
      enrolled, LAIV recipients missed 324-902 and 150 fewer days of day care per 1,000
      children than those of placebo and IIV recipients, respectively; parents of LAIV
      recipients missed 197-340 and 76 fewer days of work per 1,000 children than those
      of placebo and IIV recipients, respectively. Influenza illness in European and
      Israeli children 2-17 years of age resulted in a considerable absenteeism and
      healthcare utilization that was similar across the countries studied. These data
      underscore the potential benefits of annual vaccination of children against
      influenza.

PMID- 24091747
TI  - Cancer cell metabolism: implications for therapeutic targets.
AB  - Cancer cell metabolism is characterized by an enhanced uptake and utilization of
      glucose, a phenomenon known as the Warburg effect. The persistent activation of
      aerobic glycolysis in cancer cells can be linked to activation of oncogenes or
      loss of tumor suppressors, thereby fundamentally advancing cancer progression. In
      this respect, inhibition of glycolytic capacity may contribute to an anticancer
      effect on malignant cells. Understanding the mechanisms of aerobic glycolysis may
      present a new basis for cancer treatment. Accordingly, interrupting lactate
      fermentation and/or other cancer-promoting metabolic sites may provide a
      promising strategy to halt tumor development. In this review, we will discuss
      dysregulated and reprogrammed cancer metabolism followed by clinical relevance of
      the metabolic enzymes, such as hexokinase, phosphofructokinase, pyruvate kinase
      M2, lactate dehydrogenase, pyruvate dehydrogenase kinase and glutaminase. The
      proper intervention of these metabolic sites may provide a therapeutic advantage
      that can help overcome resistance to chemotherapy or radiotherapy. 

PMID- 24091748
TI  - In vivo action of IL-27: reciprocal regulation of Th17 and Treg cells in collagen
      induced arthritis.
AB  - Interleukin (IL)-27 is a novel cytokine of the IL-6/IL-12 family that has been
      reported to be involved in the pathogenesis of autoimmune diseases and has a
      pivotal role as both a pro- and anti-inflammatory cytokine. We investigated the
      in vivo effects of IL-27 on arthritis severity in a murine collagen-induced
      arthritis (CIA) model and its mechanism of action regarding control of regulatory
      T (Tregs) and IL-17-producing T helper 17 (Th17) cells. IL-27-Fc-treated CIA mice
      showed a lower severity of arthritis. IL-17 expression in the spleens was
      significantly decreased in IL-27-Fc-treated CIA mice compared with that in the
      CIA model. The Th17 population was decreased in the spleens of IL-27-Fc-treated
      CIA mice, whereas the CD4(+)CD25(+)Foxp3(+) Treg population increased. In vitro
      studies revealed that IL-27 inhibited IL-17 production in murine CD4(+) T cells,
      and the effect was associated with retinoic acid-related orphan receptor gammaT
      and signal transducer and activator of transcription 3 inhibition. In contrast,
      fluorescein isothiocyanate-labeled forkhead box P3 (Foxp3) and IL-10 were
      profoundly augmented by IL-27 treatment. Regarding the suppressive capacity of
      Treg cells, the proportions of CTLA-4(+) (cytotoxic T-lymphocyte antigen 4), PD
      1(+) (programmed cell death protein 1) and GITR(+) (glucocorticoid-induced tumor
      necrosis factor receptor) Tregs increased in the spleens of IL-27-Fc-treated CIA
      mice. Furthermore, in vitro differentiated Treg cells with IL-27 exerted a more
      suppressive capacity on T-cell proliferation. We found that IL-27 acts as a
      reciprocal regulator of the Th17 and Treg populations in CD4(+) cells isolated
      from healthy human peripheral blood mononuclear cells (PBMCs), as well as from
      humans with rheumatoid arthritis (RA) PBMCs. Our study suggests that IL-27 has
      the potential to ameliorate overwhelming inflammation in patients with RA through
      a reciprocal regulation of Th17 and Treg cells. 

PMID- 24091749
TI  - Choosing wisely, and soon.

PMID- 24091750
TI  - Balloon-occluded retrograde transvenous obliteration of gastric varices.
AB  - Balloon-occluded retrograde transvenous obliteration (BRTO) of gastric varices is
      an image-guided transcatheter procedure used to treat gastric varices with
      sclerosants rather than decompression of the portal venous system. The history of
      its development, relevant portal venous, and systemic venous anatomic
      considerations, techniques, indications, and early results will be reviewed. In
      addition, the status of the practice of BRTO in the United States will be
      discussed. 

PMID- 24091751
TI  - MR guidance and thermometry of percutaneous laser disc decompression in open MRI:
      an ex vivo study.
AB  - PURPOSE: To assess the feasibility of guidance and thermometry by open 1.0 T
      magnetic resonance (MR) imaging during percutaneous laser disc decompression
      (PLDD). METHODS: A fluoroscopic proton-density-weighted turbo spin echo sequence
      was used for positioning a laser fiber and a reference thermosensor within the
      targeted spinal disc. In 30 lumbar discs from human donors, nonspoiled gradient
      echo (GRE) sequences with different echo times (TE) were compared to monitor
      thermal laser effects (Nd:YAG laser, 1,064 nm). Temperature distribution was
      visualized in real time on the basis of T1-weighted images and the proton
      resonance frequency (PRF) technique. Image quality, temperature accuracy, and
      correlation with macroscopic lesion sizes were analyzed. Image quality was
      confirmed in healthy volunteers. RESULTS: MR-guided placement of the laser fiber
      in the center of the targeted disk was precise. Best overall PLDD results
      considering image quality (contrast-to-noise ratio), temperature accuracy (R (2)
      = 0.96), and correlation between the macroscopic and MR lesions (R (2) = 0.63)
      were achieved with TE at 7 ms. The same TE value also gave the best image quality
      with healthy volunteers. CONCLUSION: Instrument guidance and PRF-based
      thermometry of PLDD in the lumbar spine are feasible and accurate. Open 1.0 T MR
      imaging with fast spin-echo and GRE sequence designs may render laser
      discectomies more effective and controllable.

PMID- 24091752
TI  - Transient ischemic rectitis as a potential complication after prostatic artery
      embolization: case report and review of the literature.
AB  - Prostatic artery embolization (PAE) is an alternative treatment for benign
      prostatic hyperplasia. Complications are primarily related to non-target
      embolization. We report a case of ischemic rectitis in a 76-year-old man with
      significant lower urinary tract symptoms due to benign prostatic hyperplasia,
      probably related to nontarget embolization. Magnetic resonance imaging revealed
      an 85.5-g prostate and urodynamic studies confirmed Inferior vesical obstruction.
      PAE was performed bilaterally. During the first 3 days of follow-up, a small
      amount of blood mixed in the stool was observed. Colonoscopy identified rectal
      ulcers at day 4, which had then disappeared by day 16 post PAE without treatment.
      PAE is a safe, effective procedure with a low complication rate, but
      interventionalists should be aware of the risk of rectal nontarget embolization.

PMID- 24091753
TI  - Management of painful pelvic bone metastasis of renal cell carcinoma using
      embolization, radio-frequency ablation, and cementoplasty: a prospective
      evaluation of efficacy and safety.
AB  - PURPOSE: To measure the impact on pain relief and patient quality of life using
      embolization radio-frequency ablation and cementoplasty (ERC) for local
      combination therapeutic management of painful pelvic bone metastasis of renal
      cell carcinoma (RCC). MATERIALS AND METHODS: This prospective monocentric
      registry was approved by our Local Institutional Review Board. Between January
      2008 and January 2013, all consecutive patients who fully met the inclusion
      criteria were enrolled in the ERC-procedure prospective registry. They were
      assigned to follow-up at discharge and again at 1 and 6 months. Efficacy was
      evaluated using a pain visual analog scale (VAS), and narcotic consumption and
      quality of life were assessed using the Brief Pain Inventory questionnaire.
      RESULTS: Fifty-two patients were enrolled, among whom 58 lesions were treated.
      Technical success was obtained in all procedures. The median VAS score decreased
      from 7 +/- 1.4 (ranges 5-10) at baseline to 3 +/- 1.5 (ranges 0-6) at discharge,
      2 +/- 1.5 (ranges 0-5) at 1 month (p < 0.0001), and 2 +/- 1.6 (ranges 0-5) at 6
      months. In 28 patients (54 %), narcotic consumption was halved at discharge and
      halved in 40 (77 %) patients at 1 and 6 months compared with baseline. Five
      patients had complete pain relief at 1 month. A major improvement in quality of
      life, especially regarding mood and motion, was observed in all patients.
      CONCLUSION: This specific approach to painful bone metastasis is efficient and
      safe and yields sustained results. The ERC procedure could be suggested for
      patients with RCC bone metastasis.

PMID- 24091754
TI  - Splenomegaly-associated thrombocytopenia after hepatic yttrium-90
      radioembolization.
AB  - PURPOSE: Thrombocytopenia is often observed after yttrium-90 radioembolization
      (RE). Possible mechanisms include radiation toxicity to the bone marrow,
      consumption in the liver due to local radiation effects, and sequestration in the
      spleen. We sought to identify the causative factors. MATERIALS AND METHODS:
      Patients with complete baseline and 3-month post-RE imaging and laboratory data
      were included in this retrospective analysis. Univariate and multivariate
      regression analyses were performed on clinical, procedural, and imaging data.
      RESULTS: A total of 116 patients were identified (65 male, 51 female; median age
      64 years). Forty-six patients were treated for primary and 70 for metastatic
      liver malignancy. Of these, 86 were treated with resin and 30 with glass
      microspheres; median activity was 1.85 GBq. Eighty-three patients underwent whole
      liver treatment. Maximum individual change in platelet count was -20.2 % leading
      to new or increased grade of thrombocytopenia in 48 patients (41.4 %) by National
      Cancer Institute Common Toxicity Criteria for Adverse Events version 4.02
      criteria. Independent risk factors for decreased platelet count included change
      in spleen volume (median change +17.5 %; p = 0.001) and whole-liver (rather than
      lobar or segmental) treatment (p = 0.025). Administered activity and absorbed
      dose were not associated with change in platelet count. The change in spleen
      volume itself was associated with previous epidermal growth factor receptor
      inhibitor treatment (p = 0.002), whole-liver absorbed dose (p = 0.027), and
      multiple-line chemotherapy (0.012) for whole-liver treatments only. CONCLUSION:
      Post-RE treatment increase of spleen volume is correlated with decreased
      peripheral platelet count suggesting a mechanism of increased portal hypertension
      and hypersplenism being responsible.

PMID- 24091755
TI  - Thermal versus impedance-based ablation of renal cell carcinoma: a meta-analysis.
AB  - BACKGROUND: Percutaneous radiofrequency ablation (RFA) of renal carcinoma has
      become an established treatment modality. However, thermal (TB) versus impedance
      based (IB)-RF generators have not been previously compared. METHODS: A literature
      search on the application of RFA for renal masses using TB or IB-RF generators
      was performed. The safety, efficacy, and long-term outcomes of TB versus IB-based
      RFA were assessed using the outcome measures of technical success, local
      recurrence rate, complications, and preservation of renal function. RESULTS:
      Across the 27 included studies, pooled results suggested comparable results for
      technical success (TB-RFA 98.53 % vs. IB-RFA 98.78 %, P = 0.9813). Clinical
      efficacy results were also similar across both generators (91.0 % TB-RFA vs. 91.5
      % IB-RFA; P = 0.73). At follow-up, no differences in renal function (relative
      risk [RR] 0.5, 95 % confidence interval [CI] 0.45-5.48), and local recurrence (RR
      0.717, 95 % CI 0.49-1.50) were observed. The pooled proportion of overall
      complication rates was 13.1 % for TB-RFA and 11.5 % for IB-RFA. CONCLUSION: No
      differences in the observed parameters were found either during surgery or at
      follow-up.

PMID- 24091756
TI  - Long-term outcome of endovascular repair of popliteal artery aneurysm presents a
      credible alternative to open surgery.
AB  - PURPOSE: Endovascular repair of popliteal artery aneurysms (PAA) has become
      increasingly popular; however, long-term patency and limb salvage rates are not
      fully established. METHODS: A retrospective review of all endovascular PAA
      repairs at our institution (from 2005 to 2012) identified 34 PAAs in 26 patients,
      of which 32 % presented with acute symptoms. PAA were repaired with either
      Hemobahn((r)) or Viabahn((r)) endografts, using an entirely percutaneous
      approach. All patients were given Clopidogrel and/or aspirin postoperatively.
      Mean follow-up duration was 40 (range 4-86) months. Kaplan-Meier analysis was
      used to determine primary patency, secondary patency, and limb salvage rates.
      Complications and reintervention rates also were examined. RESULTS: At 1, 3, and
      5 years follow-up, the primary graft patency was 88, 82, and 82 %, respectively,
      and secondary patency was 90, 86, and 86 %. Amputation-free survival at 1, 3, and
      5 years was 97, 94, and 94 %, respectively. Technical success was achieved in 100
      %. There were five graft occlusions: one was asymptomatic, one was treated with
      thrombolysis successfully, and one was thrombolysed but reoccluded resulting in
      nondisabling claudication. Two were not suitable for thrombolysis and required
      amputation. The overall reintervention rate was 12 %. CONCLUSIONS: The primary
      and secondary patency rates of endovascular repair of PAA are equivalent to the
      reported outcome of open repair. Reintervention and limb salvage rate appears
      better than open repair. With improved long-term outcomes, endovascular repair
      can be considered a credible treatment strategy for routine uncomplicated PAA.

PMID- 24091758
TI  - Endovascular treatment in two cases of bilateral ischemic stroke.
AB  - Acute bilateral intracranial large artery occlusion is a rare occurrence that can
      lead to bihemispheric ischemia and potentially devastating functional
      consequences. We discuss two cases that initially presented with unilateral
      symptoms and did not show signs of bilateral arterial occlusions on the initial
      MRI imaging. This became evident while performing the angiographic study at the
      beginning of the endovascular procedure. Both patients were successfully treated
      with bilateral mechanical thrombectomy as a complement to intravenous
      thrombolysis. We describe our method of simultaneous sequential bilateral
      thrombectomy. To our knowledge, this is the first report of successful
      endovascular therapy in bilateral ischemic stroke. 

PMID- 24091757
TI  - Primary stent angioplasty of the inferior vena cava after liver transplantation
      and liver resection.
AB  - PURPOSE: This study evaluated technical efficacy and safety of stent angioplasty
      of the inferior vena cava (IVC) after liver transplantation or liver resection
      and analysis of changes in creatinine levels and patients' weight. METHODS:
      Between October 2004 and February 2011, 16 patients (mean age, 52.6 years) with
      symptomatic IVC stenoses after liver transplantation (n = 10) or liver resection
      (n = 6) were subjected to stent angioplasty. Enrollment criteria included edema
      and/or ascites. The smallest diameter of the IVC, serum creatinine values, and
      patients' weight were assessed before and after stent placement and respective
      values were compared. Technical and clinical success, patency rates, related
      complications, and patients' survival were analyzed. RESULTS: Stent placement was
      technically successful in 16 patients (100 %). Clinical success was achieved in
      13 patients (81.25 %), reflecting two patients with early restenosis and one
      patient suffering from thrombosis distal to the stent. Mean follow-up was 372
      days. Primary patencies were 75 % (n = 12). Primary assisted patencies were 93.75
      % (n = 15). Serum creatinine levels decreased significantly (p = 0.01) from 1.68
      mg/dl before to 1.08 mg/dl after stent placement. Patients' weight decreased
      (mean 2.1 %). No angioplasty-related complications occurred. CONCLUSIONS: Stent
      angioplasty of the IVC is an effective and safe treatment of stenoses after liver
      transplantation and resection and has a positive effect on creatinine levels.

PMID- 24091759
TI  - A prospective randomized trial of catheter-directed thrombolysis with additional
      balloon dilatation for iliofemoral deep venous thrombosis: a single-center
      experience.
AB  - PURPOSE: Catheter-directed thrombolysis (CDT) is effective for acute iliofemoral
      deep venous thrombosis (DVT), but CDT remains partially effective for subacute
      DVT. The aim of this study was to conduct a prospective randomized controlled
      single-centre clinical trial to compare CDT alone with CDT with additional
      balloon dilatation for the treatment of iliofemoral DVT. METHODS: The trial was
      performed between February 2007 and January 2011. Iliofemoral DVT patients
      lacking effective therapy before enrollment were randomly assigned either to CDT
      (control group) or to CDT with additional balloon dilatation (intervention
      group). Insufficiency Epidemiological and Economic Study-Quality of Life (VEINES
      QOL), Severity of Venous Lower Limb Symptoms (VEINES-Sym), 36-Item Short-Form
      Health Survey (SF-36), and Villalta scores were obtained at scheduled follow-up.
      RESULTS: Seven hundred twenty-two patients were screened, and 386 eligible
      patients were randomized. No significant difference for mean total Villalta score
      was observed between the intervention group (4.20 +/- 3.05) and the control group
      (4.89 +/- 3.45). However, post hoc analysis of the scores in subacute patients
      showed significant differences between the intervention group and the control
      group from 1 month (6.79 +/- 4.23, 8.28 +/- 5.03, P = 0.02) to 24 months (4.21 +/
      3.08, 5.67 +/- 3.71, P = 0.006). A significant difference was also observed in
      subacute patients at the end of follow-up for VEINES-QOL/Sym (52.87 +/- 6.52,
      50.31 +/- 6.07, P = 0.009; 51.87 +/- 6.37, 49.72 +/- 5.96, P = 0.02) and SF-36
      PCS/MCS (45.02 +/- 12.07, 41.13 +/- 11.68, P = 0.03; 53.26 +/- 11.43, 49.50 +/-
      11.06, P = 0.03). CONCLUSION: Subacute iliofemoral DVT patients lacking effective
      therapy during acute phase, might receive more benefits from CDT with additional
      balloon dilatation. However, CDT alone is highly effective for acute patients.

PMID- 24091760
TI  - Endovascular aortic repair with the chimney technique using the ultra low-profile
      Ovation stent-graft for juxtarenal aneurysms having small iliac access vessels.
AB  - PURPOSE: To report the first experience using the chimney technique in
      combination with the latest-generation low-profile stent-graft to seal abdominal
      aortic aneurysms having a very short neck (proximal sealing zone) and difficult
      access due to very small iliac vessels. MATERIALS AND METHODS: Use of an ultra
      low-profile 14F delivery aortic stent-graft system (Ovation; Trivascular, Santa
      Rosa, CA) with chimneys to the lowermost renal arteries in two patients who were
      not anatomically suitable for endovascular aortic aneurysm repair (EVAR) and too
      frail for open surgery. RESULTS: Implantation of stent-grafts and chimneys was
      technically successful without endoleak or other postinterventional
      complications. Follow-up after >1 year confirmed complete aneurysm exclusion,
      shrinkage of the aneurysm sac, and patent renal perfusion by way of the chimney.
      CONCLUSION: Ultra low-profile aortic stent-graft systems are particularly helpful
      in case of inadequate small iliac access vessels and allow EVAR for short-necked
      aortic aneurysms if technical contraindications obviate FEVAR and physical
      impairment discourages open surgical repair.

PMID- 24091761
TI  - Residual pathways after spinal cord injury are not always clinically assessed.

PMID- 24091763
TI  - Gender differences in substance abuse treatment and barriers to care among
      persons with substance use disorders with and without comorbid major depression.
AB  - OBJECTIVES: To compare substance use disorders (SUD) treatment patterns and
      barriers to such treatment among men and women with SUD with and without comorbid
      major depressive episodes (MDE) in a community sample. METHODS: Using data from
      adult participants in the National Survey on Drug Use and Health 2005-2010, we
      investigated differences by sex in the association of MDE comorbidity with SUD on
      patterns of, perceived unmet need for, and the perceived barriers to SUD
      treatments. RESULTS: Compared with participants with SUD without MDE, both men
      and women with comorbid SUD and MDE were more likely to use SUD services or to
      report an unmet need for such treatment. Sex modified the association of
      comorbidity and treatment patterns: males with MDE comorbidity had a greater
      likelihood of emergency room visits and use of inpatient services than females.
      Barriers to substance treatment were remarkably similar for males and females in
      both the SUD without MDE group and with MDE group, with attitudinal factors being
      the most common barriers. CONCLUSIONS: Comorbidity with MDE seems to be an
      important predictor of service utilization and perceived need for SUD treatment
      in both men and women. The association of comorbidity with the use of some types
      of services, however, seems to vary according to sex. The findings have
      implications for the design of sex-specific SUD treatment programs.

PMID- 24091765
TI  - Phototransformation of azoxystrobin fungicide in organic solvents.
      Photoisomerization vs. photodegradation.
AB  - Azoxystrobin is a systemic fungicide that has a tendency to accumulate at the
      surface of crop leaves or inside their cuticle where it undergoes
      photodegradation. Its photochemistry was investigated in n-heptane and
      isopropanol to mimic the polarity of wax leaves. Using analytical and kinetic
      data, we demonstrate that azoxystrobin (isomer E) undergoes efficient
      photoisomerization into the isomer Z with a quantum yield of 0.75 +/- 0.08. This
      value is 30-fold higher than that reported in aqueous solution. The
      photoisomerization of isomer Z into azoxystrobin is more efficient with a
      chemical yield of 0.95 +/- 0.1. In addition, a pseudo photostationary equilibrium
      is reached when the ratio [azoxystrobin]/[isomer Z] is 2.0 +/- 0.1.
      Photodegradation also takes place from azoxystrobin (quantum yield = 0.073 +/-
      0.008). Photoproducts mainly arise from bond cleavage between rings and from
      demethylation of the ether with or without saturation of the acrylate double
      bond. Theoretical calculations were undertaken to investigate the
      photoisomerization mechanism and the solvent effect. These data show that the
      photochemical reactivity of azoxystrobin is enhanced when the solvent polarity
      decreases and thus should be significant in leaf waxes. 

PMID- 24091764
TI  - Comparative safety of benzodiazepines and opioids among veterans affairs patients
      with posttraumatic stress disorder.
AB  - OBJECTIVES: Although Veterans Affairs (VA) patients with posttraumatic stress
      disorder (PTSD) are prescribed benzodiazepines and opioids in addition to
      recommended pharmacotherapies, little is known about the safety of these
      medications. This study compared the 2-year incidence of adverse events among VA
      patients with PTSD exposed to combinations of selective serotonin reuptake
      inhibitors (SSRIs) or serotonin/norepinephrine reuptake inhibitors (SNRIs),
      benzodiazepines, and opioids. METHODS: This retrospective cohort study used VA
      administrative data from 2004 to 2010 to identify and follow 5236 VA patients
      with PTSD with new episodes of (1) SSRIs/SNRIs only; (2) concurrent SSRIs/SNRIs
      and benzodiazepines; and (3) concurrent SSRIs/SNRIs, benzodiazepines, and
      opioids. Outcome measures were the 2-year incidence and adjusted hazard ratios
      (AHR) of mental health and medicine/surgery hospitalizations, emergency
      department visits, harmful events (eg, injuries and death), and any adverse event
      after adjustment for demographics, clinical covariates, and adverse event
      history. RESULTS: Compared with SSRIs/SNRIs only, the adjusted risk of mental
      health hospitalizations (AHR: 1.87; 95% confidence interval [CI]: 1.37-2.53) was
      greater among patients prescribed SSRIs/SNRIs and benzodiazepines concurrently.
      The AHR of mental health hospitalizations (AHR: 2.00; 95% CI: 1.35-2.98),
      medicine/surgery hospitalizations (AHR: 4.86; 95% CI: 3.30-7.14), emergency
      department visits (AHR: 2.01; 95% CI: 1.53-2.65), any harmful event (2.92; 95%
      CI: 2.21-3.84), and any adverse event (AHR: 2.65; 95% CI: 2.18-3.23) were all
      significantly greater among patients prescribed SSRIs/SNRIs, benzodiazepines, and
      opioids than among those prescribed SSRIs/SNRIs only. CONCLUSIONS: Concurrently
      prescribing SSRIs/SNRIs, benzodiazepines, and opioids among patients with PTSD is
      associated with adverse events. Although efforts are warranted to monitor
      patients who are prescribed combinations of these medications to prevent adverse
      events, these results should be interpreted with caution until they are
      replicated.

PMID- 24091767
TI  - Cyanamide route to calcium-manganese oxide foams for water oxidation.
AB  - In nature, photosynthetic water oxidation is efficiently catalysed at a protein
      bound MU-oxido Mn4Ca cluster. This cluster consists of earth abundant, non-toxic
      elements and serves as a paragon for development of synthetic catalysts. In this
      study we developed porous calcium-manganese oxides with a unique foam-like
      nanostructure prepared via a facile and robust synthetic route using cyanamide as
      a porogen. A series of such oxide foams annealed at different temperatures was
      characterized by TEM, SEM, XRD, N2 physisorption, and X-ray absorption
      spectroscopy (XAS) in order to correlate crystallinity, atomic structure, surface
      area and oxidation state of the materials with catalytic activity. Some of the
      resulting Ca-Mn oxides show high activity as catalysts for water oxidation in the
      presence of cerium(iv) ammonium nitrate as a non-oxo transfer oxidant. An
      amorphous calcium-manganese-oxide foam with 130 m(2) g(-1) surface area and Mn
      oxidation state of +3.6 was identified to be most active; its activity is
      superior to previously reported Ca-Mn oxides. At the atomic level, this material
      shares structural motifs with the biological paragon as revealed by dual-edge XAS
      at the Mn and Ca K-edge. Rather than nanostructure and surface area, the atomic
      structure of the Ca-Mn oxide and the extent of structural order appear to be
      crucial determinants of catalytic activity. Fully disordered low-valent Mn
      materials as well as high-valent but crystalline Mn-Ca oxides are unreactive.
      Highly disordered variants of layered manganese oxide with Ca and water molecules
      interfacing layer fragments are most reactive. 

PMID- 24091766
TI  - GABA-A receptor impairment in cerebellar ataxia with anti-glutamic acid
      decarboxylase antibodies.
AB  - Antibodies against glutamic acid decarboxylase (GAD-Abs) are associated with
      cerebellar ataxia, which is refractory to treatment with GABAergic drugs. To
      investigate the GABAergic neuronal system in vivo, we performed a combined
      positron emission tomography (PET) study with [(11)C]-flumazenil and [(18)F]
      fluorodeoxyglucose (FDG) in three patients with cerebellar ataxia with GAD-Abs.
      The GABA-A receptor function was investigated using flumazenil, which is a
      selective GABA-A receptor ligand, while FDG-PET using a three-dimensional
      stereotactic surface projection analysis was performed to estimate the metabolic
      rates of glucose (MRGlc) in the patients. GABAergic drugs showed no efficacy for
      the cerebellar ataxia in all three patients, and all three displayed a
      significant decrease in flumazenil binding in the cerebellum. No MRGlc decrease
      in the cerebellum was found in the two patients who presented with amelioration
      of cerebellar ataxia following intravenous immunoglobulin (IVIG) therapy, whereas
      a significant MRGlc decrease in the cerebellar hemisphere was observed in another
      patient who showed severe cerebellar atrophy on magnetic resonance images and no
      response to the IVIG therapy. The decreased flumazenil binding in the present
      patients indicated cerebellar GABA-A receptor impairment, which may be due to
      either neuronal cell loss, as demonstrated by the decreased MRGlc, or a
      dysfunction in GABAergic neuronal inhibition. Although GAD-Abs have been
      postulated to prevent the synthesis of GABA, resulting in decreased GABAergic
      transmission, the GABA-A receptor impairment may play another pathogenic role in
      cerebellar ataxia associated with GAD-Abs resulting in a condition refractory to
      GABAergic drug therapy.

PMID- 24091768
TI  - AMG 900, pan-Aurora kinase inhibitor, preferentially inhibits the proliferation
      of breast cancer cell lines with dysfunctional p53.
AB  - Aurora kinases play important roles in cell division and are frequently
      overexpressed in human cancer. AMG 900 is a novel pan-Aurora kinase inhibitor
      currently being tested in Phase I clinical trials. We aimed to evaluate the in
      vitro activity of AMG 900 in a panel of 44 human breast cancer and immortalized
      cell lines and identify predictors of response. AMG 900 inhibited proliferation
      at low nanomolar concentrations in all cell lines tested. Response was further
      classified based on the induction of lethality. 25 cell lines were classified as
      highly sensitive (lethality at 10 nM of AMG 900 >10 %), 19 cell lines as less
      sensitive to AMG 900 (lethality at 10 nM of AMG 900 <10 %). Traditional molecular
      subtypes of breast cancer did not predict for this differential response. There
      was a weak association between AURKA amplification and response to AMG 900
      (response ratio = 2.53, p = 0.09). mRNA expression levels of AURKA, AURKB, and
      AURKC and baseline protein levels of Aurora kinases A and B did not significantly
      associate with response. Cell lines with TP53 loss of function mutations (RR =
      1.86, p = 0.004) and low baseline p21 protein levels (RR = 2.28, p = 0.0004) were
      far more likely to be classified as highly sensitive to AMG 900. AMG 900 induced
      p53 and p21 protein expression in cell lines with wt TP53. AMG 900 caused the
      accumulation of cells with >4 N DNA content in a majority of cell lines
      independently of sensitivity and p53 status. AMG 900 induced more pronounced
      apoptosis in highly sensitive p53-dysfunctional cell lines. We have found that
      AMG 900 is highly active in breast cancer cell lines and that TP53 loss of
      function mutations as well as low baseline expression of p21 protein predict
      strongly for increased sensitivity to this compound in vitro. 

PMID- 24091769
TI  - Radiation- and anthracycline-induced cardiac toxicity and the influence of ErbB2
      blocking agents.
AB  - In Her2-positive breast cancer patients, inhibition of epidermal growth factor
      receptor 2 (ErbB2)-signaling is often combined with chemotherapy and
      radiotherapy. The risk of cardiac toxicity after anthracyclines and radiotherapy
      is recognized, but little is known about increased risk when these treatments are
      combined with ErbB2 inhibition. This study investigated whether ErbB2 inhibition
      increased radiation or anthracycline-induced toxicity. In an in vitro study,
      human cardiomyocytes were treated with irradiation or doxorubicin, alone or in
      combination with trastuzumab, and evaluated for cell survival and growth. Groups
      of mice received 0 or 14 Gy to the heart, alone or in combination with lapatinib,
      or 3 * 4 mg/kg doxorubicin alone or in combination with lapatinib. Mice were
      evaluated 40 weeks after treatment for cardiac damage. Changes in cardiac
      function ((99m)Tc-Myoview gated SPECT) were related to histomorphology and
      microvascular damage. Radiation or doxorubicin-induced cardiomyocyte toxicity (in
      vitro) were not exacerbated by trastuzumab. Cardiac irradiation of mice decreased
      microvascular density (MVD) and increased endothelial damage in surviving
      capillaries (decrease alkaline phosphatase expression and increased von
      Willebrand factor), but these changes were not exacerbated by lapatinib.
      Inflammatory responses in the irradiated epicardium (CD45+ and F4/80+ cells) were
      significantly reduced in combination with lapatinib. Irradiation, doxorubicin,
      and lapatinib each induced cardiac fibrosis but this was not further enhanced
      when treatments were combined. At the ultra-structural level, both lapatinib and
      doxorubicin induced mitochondrial damage, which was enhanced in combined
      treatments. Lapatinib alone also induced mild changes in cardiac function but
      this was not enhanced in the combined treatments. Trastuzumab did not enhance
      direct radiation or anthracycline toxicity of cardiomyocytes in vitro. Lapatinib
      did not enhance the risk of radiation or anthracycline-induced cardiac toxicity
      in mice up to 40 weeks after treatment, but mitochondrial damage was more severe
      after doxorubicin combined with lapatinib. 

PMID- 24091770
TI  - The development of path integration: combining estimations of distance and
      heading.
AB  - Efficient daily navigation is underpinned by path integration, the mechanism by
      which we use self-movement information to update our position in space. This
      process is well understood in adulthood, but there has been relatively little
      study of path integration in childhood, leading to an underrepresentation in
      accounts of navigational development. Previous research has shown that
      calculation of distance and heading both tend to be less accurate in children as
      they are in adults, although there have been no studies of the combined
      calculation of distance and heading that typifies naturalistic path integration.
      In the present study, 5-year-olds and 7-year-olds took part in a triangle
      completion task, where they were required to return to the start point of a multi
      element path using only idiothetic information. Performance was compared to a
      sample of adult participants, who were found to be more accurate than children on
      measures of landing error, heading error, and distance error. Seven-year-olds
      were significantly more accurate than 5-year-olds on measures of landing error
      and heading error, although the difference between groups was much smaller for
      distance error. All measures were reliably correlated with age, demonstrating a
      clear development of path integration abilities within the age range tested.
      Taken together, these data make a strong case for the inclusion of path
      integration within developmental models of spatial navigational processing. 

PMID- 24091771
TI  - The sound-induced phosphene illusion.
AB  - Crossmodal illusions clearly show how perception, rather than being a modular and
      self-contained function, can be dramatically altered by interactions between
      senses. Here, we provide evidence for a novel crossmodal "physiological"
      illusion, showing that sounds can boost visual cortical responses in such a way
      to give rise to a striking illusory visual percept. In healthy participants, a
      single-pulse transcranial magnetic stimulation (sTMS) delivered to the occipital
      cortex evoked a visual percept, i.e., a phosphene. When sTMS is accompanied by
      two auditory beeps, the second beep induces in neurologically unimpaired
      participants the perception of an illusory second phosphene, namely the sound
      induced phosphene illusion. This perceptual "fission" of a single phosphene, due
      to multiple beeps, is not matched by a "fusion" of double phosphenes due to a
      single beep, and it is characterized by an early auditory modulation of the TMS
      induced visual responses (~80 ms). Multiple beeps also induce an illusory feeling
      of multiple TMS pulses on the participants' scalp, consistent with an audio
      tactile fission illusion. In conclusion, an auditory stimulation may bring about
      a phenomenological change in the conscious visual experience produced by the
      transcranial stimulation of the occipital cortex, which reveals crossmodal
      binding mechanisms within early stages of visual processing. 

PMID- 24091772
TI  - Optimizing the control of high-ID movements: rethinking the power of the visual
      display.
AB  - A recent experiment by Boyle et al. (Exp Brain Res 223:377-387, 2012a)
      demonstrated that providing a sine-wave template for participants to follow
      enhances performance and transfer on difficult (ID = 6) Fitts tasks. Another
      experiment (Fernandez and Bootsma in Acta Psychol 129:217-227, 2008) demonstrated
      the effectiveness of applying a nonlinear transformation of the visual feedback
      provided to participants executing difficult aiming movements. The present
      experiment was designed to determine whether these two enhancements when used
      together would provide further enhancements to difficult aiming movements.
      Participants were randomly assigned to one of the three acquisition conditions.
      Participants in the Fitts and Fittslog condition were asked to flex/extend their
      arm in the horizontal plane at the elbow joint (wrist stabilized) in an attempt
      to move back and forth between two targets as quickly and accurately as possible.
      In the Sinelog condition, participants were asked to track a sine-wave pattern.
      The timing for Sinelog conditions was set to result in total times (movement time
      + dwell time) similar to that anticipated for the Fittslog condition. The
      feedback displays for Fittslog and Sinelog groups were subjected to a nonlinear
      transformation, but not for the Fitts group. Following 54 acquisition trials
      (17.5 s each) under their assigned condition, Test 1 was conducted under the same
      conditions as the participant experienced during the acquisition trials and Test
      2 was conducted under Fitts conditions with the nonlinear transformation of the
      display data. Test 3 was conducted under typical Fitts conditions with no
      transformation of the display data. The results for Tests 1 and 2 indicated that
      total time and movement time for the Fittslog and Sinelog groups were reduced
      relative to the Fitts condition. In addition, dwell time was significantly lower,
      a larger proportion of movement time was spent in the acceleration portion of the
      movement, and normalized peak velocity was significantly lower for the
      participants in the Sinelog condition than for participants in the Fittslog
      condition. On Test 3, an untransformed Fitts condition was imposed; the Sinelog
      group outperformed the Fittslog condition on all variables except hits, endpoint
      variability, and peak velocity where the Fittslog and Sinelog groups performed
      similarly. 

PMID- 24091773
TI  - Leakage of decision uncertainty into movement execution in Parkinson's disease?
AB  - The concept of segregated basal ganglia-cortical loops entails that functional
      disturbances may result from abnormal processing within loops, but also from
      abnormal communication between loops. Cognitive and motor processes subserved by
      different basal ganglia-frontal loops may interfere with one another as a result
      of such abnormal communication, leakage, between loops. In Parkinson's disease,
      movement execution has been found susceptible to decision uncertainty, attributed
      to this mechanism. Here, we evaluate whether this mechanism of abnormal coupling
      or leakage extends to perceptual decision-making with trial-by-trial control of
      decision uncertainty. We examined 10 Parkinson's disease (PD) patients and
      healthy control subjects in a random-dot motion direction discrimination task
      with concurrent EEG recording. Random-dot motion was manipulated to make
      direction discrimination easy or difficult. Reaction times (RT) and movement
      times (MT) were recorded, and EEG was analysed to extract movement-related
      potentials. Easy versus difficult direction discrimination produced robust,
      equally large RT differences in patients and controls (>400 ms), along with a
      marked difference in error rates, confirming the efficacy of the task. Effects of
      easy versus difficult discrimination on MT were comparatively small (<50 ms) and
      did not differ between groups, despite robustly slower MT in patients.
      Lateralised movement-related EEG potentials reproduced the MT difference between
      patients and controls. Together, the results do not demonstrate an enhanced
      effect of decision uncertainty onto movement execution in PD. We surmise that
      leakage of decision uncertainty into movement execution is probably task
      dependent, consistent with the view that the degree to which partial information
      is allowed to influence the motor system is under strategic control.

PMID- 24091774
TI  - Random walks on the mental number line.
AB  - The direction of influence between conceptual and motor activation, and its
      relevance for real-life activities, is still unclear. Here, we use the frequently
      reported association between small/large numbers and left/right space to
      investigate this issue during walking. We asked healthy adults to generate random
      numbers as they made lateral turns and found that (1) lateral turn decisions are
      predicted by the last few numbers generated prior to turning; (2) the intention
      to turn left/right makes small/large numbers more accessible; and (3) magnitude
      but not order of auditorily presented numbers influences the listener's turn
      selection. Our findings document a bidirectional influence between conceptual and
      motor activation and point to a hierarchically organized conceptual-motor
      activation. 

PMID- 24091775
TI  - Age-associated changes in head jerk while walking reveal altered dynamic
      stability in older people.
AB  - Many older people have impaired dynamic stability, and up to one in three people
      over 65 fall each year. It is thought that older people walk more slowly to
      compensate for reduced capabilities. Here, we investigate whether head jerk, the
      first time derivative of acceleration, can further our understanding of age
      associated changes in dynamic stability while walking. Gait parameters including
      cadence, step length, walking speed, harmonic ratios, step time variability, and
      jerk were measured in 43 young and 100 older people using accelerometers securely
      attached to the head and pelvis. Older people presented significantly (p <=
      0.004) more mediolateral (ML) head jerk, but significantly less vertical (VT)
      head jerk. The dimensionless ratio, ML/VT jerk, demonstrated superior ability (89
      % accuracy) in differentiating older from younger people. Principal component
      analysis indicated that ML/VT jerk was a distinct gait construct. ML/VT jerk was
      highly reliable, normally distributed, independent of stature or gender, and
      relatively unaffected by walking speed. In older people, reduced VT head jerk may
      indicate reduced gait vigour, and increased ML head jerk may indicate age
      associated changes to dynamic stability. The smoother head movements evident in
      our younger group may be because they were more able to rely on automatic control
      and the dynamic (pendulum-like) stability of their systems.

PMID- 24091776
TI  - Modulation of rat behaviour by using a rat-like robot.
AB  - In this paper, we study the response of a rat to a rat-like robot capable of
      generating different types of behaviour (stressful, friendly, neutral).
      Experiments are conducted in an open-field where a rat-like robot called WR-4 is
      put together with live rats. The activity level of each rat subject is evaluated
      by scoring its locomotor activity and frequencies of performing rearing (rising
      up on its hind limbs) and body grooming (body cuddling and head curling) actions,
      whereas the degree of preference of that is indicated by the robot-rat distance
      and the frequency of contacting WR-4. The moving speed and behaviour of WR-4 are
      controlled in real-time based on the feedback from rat motion. The activity level
      and degree of preference of rats for each experimental condition are analysed and
      compared to understand the influence of robot behaviour. The results of this
      study show that the activity level and degree of preference of the rat decrease
      when exposed to a stressful robot, and increase when the robot exhibit friendly
      behaviour, suggesting that a rat-like robot can modulate rat behaviour in a
      controllable, predictable way. 

PMID- 24091777
TI  - Response to letter to the editor, re: Ijaz S, et al. "Night-shift work and breast
      cancer--a systematic review and meta-analysis".

PMID- 24091778
TI  - Surface-enhanced molecular spectroscopy (SEMS) based on perfect-absorber
      metamaterials in the mid-infrared.
AB  - Surface-enhanced infrared absorption spectroscopy has attracted increased
      attention for direct access to molecular vibrational fingerprints in the mid
      infrared. Perfect-absorber metamaterials (PAMs) with multi-band spectral
      responses and significant enhancement of the local near-field intensity were
      developed to improve the intrinsic absorption cross sections of absorption
      spectrum to identify the vibrational spectra of biomolecules. To verify its
      performance, the proposed infrared PAM array was used to identify the molecular
      stretches of a Parylene C film. The resonant responses of the infrared PAMs were
      accurately tuned to the vibrational modes of the C = C target bonds. The
      vibrational stretches of the C = C moiety were observed and the auto-fluorescence
      mechanisms of the Parylene C film were monitored. The unique properties of the
      PAMs indicate that this approach is a promising strategy for surface-enhanced
      molecular absorption spectroscopy (SEMS) in the mid-infrared region and for the
      tracking of characteristic molecular vibrational modes. 

PMID- 24091779
TI  - A mathematical model of chlamydial infection incorporating movement of chlamydial
      particles.
AB  - We present a spatiotemporal mathematical model of chlamydial infection, host
      immune response, and movement of infectious particles. The resulting partial
      differential equations model both the dynamics of the infection and changes in
      infection profile observed spatially along the length of the host genital tract.
      This model advances previous Chlamydia modelling by incorporating spatial change.
      Numerical solutions and model analysis are carried out, and we present a
      hypothesis regarding the potential for treatment and prevention of infection by
      increasing chlamydial particle motility. 

PMID- 24091780
TI  - An appropriate bounded invariant region for a bistable reaction-diffusion model
      of the caspase-3/8 feedback loop.
AB  - The apoptotic caspase-3/8 feedback loop describes the core of the extrinsic pro
      apoptotic signaling pathway, an essential part of apoptosis. Latter is a
      prototype of the programmed cell death, which enables organisms to remove damaged
      or infected cells. The reaction network of the caspase-3/8 feedback loop in a
      single cell is modeled by a reaction-diffusion system, which shows a bistable
      behavior. In this work, we present an appropriate bounded invariant region for
      the bistable reaction-diffusion system in order to theoretically confirm that
      diffusion rapidly balances the concentrations of the different caspase types.
      This justifies the decomposition of the dynamics into a diffusion dominated part
      on a very short time scale and a pure reaction driven dynamics on a large time
      scale. 

PMID- 24091781
TI  - A population model of chaparral vegetation response to frequent wildfires.
AB  - The recent increase in wildfire frequency in the Santa Monica Mountains (SMM) may
      substantially impact plant community structure. Species of Chaparral shrubs
      represent the dominant vegetation type in the SMM. These species can be divided
      into three life history types according to their response to wildfires.
      Nonsprouting species are completely killed by fire and reproduce by seeds that
      germinate in response to a fire cue, obligate sprouting species survive by
      resprouting from dormant buds in a root crown because their seeds are destroyed
      by fire, and facultative sprouting species recover after fire both by seeds and
      resprouts. Based on these assumptions, we developed a set of nonlinear difference
      equations to model each life history type. These models can be used to predict
      species survivorship under varying fire return intervals. For example, frequent
      fires can lead to localized extinction of nonsprouting species such as Ceanothus
      megacarpus while several facultative sprouting species such as Ceanothus spinosus
      and Malosma (Rhus) laurina will persist as documented by a longitudinal study in
      a biological preserve in the SMM. We estimated appropriate parameter values for
      several chaparral species using 25 years of data and explored parameter
      relationships that lead to equilibrium populations. We conclude by looking at the
      survival strategies of these three species of chaparral shrubs under varying fire
      return intervals and predict changes in plant community structure under fire
      intervals of short return. In particular, our model predicts that an average fire
      return interval of greater than 12 years is required for 50 % of the initial
      Ceanothus megacarpus population and 25 % of the initial Ceanothus spinosus
      population to survive. In contrast, we predict that the Malosma laurina
      population will have 90 % survivorship for an average fire return interval of at
      least 6 years. 

PMID- 24091782
TI  - Flavonoids from fruit and vegetables: a focus on cardiovascular risk factors.
AB  - Epidemiological studies suggest that high intakes of dietary flavonoids are
      associated with decreased cardiovascular disease mortality and risk factors. Less
      is known about the cardioprotective effects of flavonoids from fruit and
      vegetables. This review summarizes data from studies which examine the effects of
      commonly consumed fruit and vegetables on cardiovascular disease risk biomarkers
      in healthy volunteers or at-risk individuals. Although flavonoids from apples,
      berries, and onions appear to impact positively on blood pressure, vascular
      function, and serum lipid levels, further research is required to find out the
      optimal quantity and food matrix for conferring substantial clinical benefit. The
      benefits from citrus flavonoids are still inconclusive. Further robust, longer
      term dietary intervention studies, with the inclusion of placebo or control arms,
      are required to improve the credibility of the findings and confirm current
      observations. An improved understanding of the impact of flavonoids from fruit
      and vegetables can help one make discerning food choices for optimal
      cardiovascular health. 

PMID- 24091784
TI  - Systematics, biogeography, and character evolution of Sparganium (Typhaceae):
      diversification of a widespread, aquatic lineage.
AB  - PREMISE OF THE STUDY: Sparganium (Typhaceae) is a genus of aquatic monocots
      containing +/-14 species, with flowers aggregated in unisexual, spherical heads,
      and habit ranging from floating to emergent. Sparganium presents an opportunity
      to investigate diversification, character evolution, and biogeographical
      relationships in a widespread temperate genus of aquatic monocots. We present a
      fossil-calibrated, molecular phylogeny of Sparganium based on analysis of two
      chloroplast and two nuclear markers. Within this framework, we examine character
      evolution in both habit and stigma number and infer the ancestral area and
      biogeographic history of the genus. * METHODS: Sequence data from two cpDNA and
      two nDNA markers were analyzed using maximum parsimony, maximum likelihood, and
      Bayesian inference. We used the program BEAST to simultaneously estimate
      phylogeny and divergence times, S-DIVA and Lagrange for biogeographical
      reconstruction, and BayesTraits to examine locule number and habit evolution. *
      KEY RESULTS: Two major clades were recovered with strong support: one composed of
      S. erectum and S. eurycarpum; and the other containing all remaining Sparganium.
      We realigned the subgenera to conform to these clades. Divergence time analysis
      suggests a Miocene crown origin but Pliocene diversification. Importantly, the
      floating-leaved habit has arisen multiple times in the genus, from emergent
      ancestors-contrary to past hypotheses. * CONCLUSIONS: Cooling trends during the
      Tertiary are correlated with the isolation of temperate Eurasian and North
      American taxa. Vicariance, long-distance dispersal, and habitat specialization
      are proposed as mechanisms for Sparganium diversification.

PMID- 24091785
TI  - Elevational patterns of genetic variation in the cosmopolitan moss Bryum
      argenteum (Bryaceae).
AB  - PREMISE OF THE STUDY: The Baas Becking tenet posits that 'everything is
      everywhere, but the environment selects' to explain cosmopolitan distributions in
      highly vagile taxa. Bryophyte species show wider distributions than vascular
      plants and include examples of truly cosmopolitan ranges, which have been
      interpreted as a result of high dispersal capacities and ecological plasticity.
      In the current study, we documented patterns of genetic structure and diversity
      in the cosmopolitan moss Bryum argenteum along an elevational gradient to
      determine if genetic diversity and structure is homogenized by intense migrations
      in the lack of ecological differentiation. * METHODS: 60 specimens were collected
      in the Sierra Nevada Mountains (Spain) between 100 and 2870 m and sequenced for
      ITS and rps4. Comparative analyses, genetic diversity estimators, and Mantel's
      tests were employed to determine the relationship between genetic variation,
      elevation, and geographic distance and to look for signs of demographic shifts. *
      KEY RESULTS: Genetic diversity peaked above 1900 m and no signs of demographic
      shifts were detected at any elevation. There was a strong phylogenetic component
      in elevational variation. Genetic variation was significantly correlated with
      elevation, but not with geographic distance. * CONCLUSIONS: The results point to
      the long-term persistence of Bryum argenteum in a range that was glaciated during
      the Late Pleistocene. Evidence for an environmentally driven pattern of genetic
      differentiation suggests adaptive divergence. This supports the Baas Becking
      tenet and indicates that ecological specialization might play a key role in
      explaining patterns of genetic structure in cosmopolitan mosses.

PMID- 24091786
TI  - A novel and efficient nicotine vaccine using nano-lipoplex as a delivery vehicle.
AB  - A number of vaccines conjugating nicotine haptens with carrier proteins have been
      developed to combat nicotine caused tobacco dependence. Some vaccines, such as
      NicVAX, NicQb, advanced into clinical trials, but none of them were successful.
      Most of those vaccines have some innate disadvantages such as low nicotine
      loading capacity, easy degradation, and vulnerable to the clearance by reticulo
      endothelial system (RES). Thus, there is undoubtedly an urgent need for
      developing novel vaccines against nicotine addiction. In this study, we assembled
      a liposome-protein based nanoparticle as a nicotine hapten delivery system. The
      nanoparticle (Scheme 1) was constructed by conjugating a model hapten carrier
      protein, bovine serum albumin (BSA), to cationic liposomes. This nano-sized
      complex, lipoplex, was characterized using zetasizer, transmission electron
      microscope (TEM), and flow cytometry. The efficacy of the lipoplex vaccine was
      evaluated in mice and compared with that of Nicotine-BSA conjugate (Nic-BSA). The
      lipoplex vaccine with Alum was able to elicit the highest NicAb titer of 11169+/
      2112, which was significantly higher than that induced by either the vaccine
      without Alum or Nic-BSA with Alum. The significant immunostimulatory effect of
      this nano-lipoplex may provide a novel strategy to improve the immunogenic
      ability of current nicotine vaccines or other vaccines using small molecules as
      immunogens.

PMID- 24091789
TI  - Diesel exhaust rapidly degrades floral odours used by honeybees.
AB  - Honeybees utilise floral odours when foraging for flowers; we investigated
      whether diesel exhaust pollution could interrupt these floral odour stimuli. A
      synthetic blend of eight floral chemicals, identified from oilseed rape, was
      exposed to diesel exhaust pollution. Within one minute of exposure the abundances
      of four of the chemicals were significantly lowered, with two components rendered
      undetectable. Honeybees were trained to recognise the full synthetic odour mix;
      altering the blend, by removing the two chemicals rendered undetectable,
      significantly reduced the ability of the trained honeybees to recognize the
      altered odour. Furthermore, we found that at environmentally relevant levels the
      mono-nitrogen oxide (NOx) fraction of the exhaust gases was a key facilitator of
      this odour degradation. Such changes in recognition may impact upon a honeybee's
      foraging efficiency and therefore the pollination services that they provide.

PMID- 24091788
TI  - Apoptotic retinal ganglion cell death in an autoimmune glaucoma model is
      accompanied by antibody depositions.
AB  - Glaucoma is characterized by death of retinal ganglion cells (RGC), but its cause
      is still unknown. We used an autoimmune glaucoma model to study (1) apoptosis,
      (2) antibody occurrence, and (3) gliosis by immunohistochemistry. Rats were
      immunized with optic nerve homogenate (ONA). At 8 days no significant apoptosis
      or difference in RGCs was noted, but ONA retinas had a significantly higher
      GFAP(+) area (p = 0.02). At 14 days, significantly more TUNEL(+) (p = 0.0002) and
      caspase 3(+) (p = 0.004) were detected in ONA animals, but no difference in RGC
      density. Distinct IgM and IgG deposits (p = 0.04) were observed in ONA retinas.
      At 22 days, a significantly higher number of TUNEL(+) cells (p = 0.0002), caspase
      3(+) cells (p = 0.0007), and concurrent a lower RGC density (p = 0.04) was noted
      in ONA animals. IgM and IgG deposits were observed in the ganglion cell layer of
      ONA retinas. The largest percentage of GFAP(+) area in the ONA group was observed
      at 22 days (p = 0.02). This data suggest that immunization with ocular antigens
      leads to apoptotic retinal ganglion cell death. Based on the co-localization of
      antibody deposits and apoptotic cells, we conclude that antibodies are engaged in
      eliciting RGC apoptosis in this animal model.

PMID- 24091790
TI  - Clinical applicability of magnetic resonance imaging in acute spinal cord trauma.
AB  - PURPOSE: To assess the clinical application of magnetic resonance imaging (MRI)
      in patients with acute spinal cord trauma (SCT) according to the type, extension,
      and severity of injury and the clinical-radiological correlation. METHODS:
      Diagnostic imaging [computed tomography (CT) and MRI] tests of 98 patients with
      acute SCT were analyzed to assess their clinical diagnostic value. The following
      radiological findings of SCT were investigated: vertebral compression fractures,
      bursts and dislocations, posterior element fractures, C1 and C2 lesions,
      vertebral listhesis, bone swelling, spinal canal compression, disk herniation,
      extradural hematoma, spinal cord contusions, spinal cord swelling, and posterior
      ligamentous complex (PLC) injuries. RESULTS: The radiological findings were
      better visualized using MRI, except for the posterior elements (p = 0.001), which
      were better identified with CT. A total of 271 lesions were diagnosed as follows:
      217 using MRI, 154 using CT, and 100 (36.9 %) using both MRI and CT. MRI detected
      117 more lesions than CT. CONCLUSION: MRI was significantly superior to CT in the
      diagnosis of bone swelling, PLC injury, disk herniation, spinal canal
      compression, spinal cord contusion and swelling present in SCT. MRI detected a
      larger number of lesions than CT and is highly useful for the diagnosis of soft
      tissue and intrathecal injuries.

PMID- 24091783
TI  - Breaking tolerance to thyroid antigens: changing concepts in thyroid
      autoimmunity.
AB  - Thyroid autoimmunity involves loss of tolerance to thyroid proteins in
      genetically susceptible individuals in association with environmental factors. In
      central tolerance, intrathymic autoantigen presentation deletes immature T cells
      with high affinity for autoantigen-derived peptides. Regulatory T cells provide
      an alternative mechanism to silence autoimmune T cells in the periphery. The TSH
      receptor (TSHR), thyroid peroxidase (TPO), and thyroglobulin (Tg) have unusual
      properties ("immunogenicity") that contribute to breaking tolerance, including
      size, abundance, membrane association, glycosylation, and polymorphisms. Insight
      into loss of tolerance to thyroid proteins comes from spontaneous and induced
      animal models: 1) intrathymic expression controls self-tolerance to the TSHR, not
      TPO or Tg; 2) regulatory T cells are not involved in TSHR self-tolerance and
      instead control the balance between Graves' disease and thyroiditis; 3) breaking
      TSHR tolerance involves contributions from major histocompatibility complex
      molecules (humans and induced mouse models), TSHR polymorphism(s) (humans), and
      alternative splicing (mice); 4) loss of tolerance to Tg before TPO indicates that
      greater Tg immunogenicity vs TPO dominates central tolerance expectations; 5)
      tolerance is induced by thyroid autoantigen administration before autoimmunity is
      established; 6) interferon-alpha therapy for hepatitis C infection enhances
      thyroid autoimmunity in patients with intact immunity; Graves' disease developing
      after T-cell depletion reflects reconstitution autoimmunity; and 7) most
      environmental factors (including excess iodine) "reveal," but do not induce,
      thyroid autoimmunity. Micro-organisms likely exert their effects via bystander
      stimulation. Finally, no single mechanism explains the loss of tolerance to
      thyroid proteins. The goal of inducing self-tolerance to prevent autoimmune
      thyroid disease will require accurate prediction of at-risk individuals together
      with an antigen-specific, not blanket, therapeutic approach. 

PMID- 24091791
TI  - Efficacy of laser-based irrigant activation methods in removing debris from
      simulated root canal irregularities.
AB  - In root canal therapy, irrigating solutions are essential to assist in
      debridement and disinfection, but their spread and action is often restricted by
      canal anatomy. Hence, activation of irrigants is suggested to improve their
      distribution in the canal system, increasing irrigation effectiveness. Activation
      can be done with lasers, termed laser-activated irrigation (LAI). The purpose of
      this in vitro study was to compare the efficacy of different irrigant activation
      methods in removing debris from simulated root canal irregularities. Twenty-five
      straight human canine roots were embedded in resin, split, and their canals
      prepared to a standardized shape. A groove was cut in the wall of each canal and
      filled with dentin debris. Canals were filled with sodium hypochlorite and six
      irrigant activation procedures were tested: conventional needle irrigation (CI),
      manual-dynamic irrigation with a tapered gutta percha cone (manual-dynamic
      irrigation (MDI)), passive ultrasonic irrigation, LAI with 2,940-nm erbium-doped
      yttrium aluminum garnet (Er:YAG) laser with a plain fiber tip inside the canal
      (Er-flat), LAI with Er:YAG laser with a conical tip held at the canal entrance
      (Er-PIPS), and LAI with a 980-nm diode laser moving the fiber inside the canal
      (diode). The amount of remaining debris in the groove was scored and compared
      among the groups using non-parametric tests. Conventional irrigation removed
      significantly less debris than all other groups. The Er:YAG with plain fiber tip
      was more efficient than MDI, CI, diode, and Er:YAG laser with PIPS tip in
      removing debris from simulated root canal irregularities. 

PMID- 24091792
TI  - Socio-economic impact of endovenous thermal ablation techniques.
AB  - Varicose veins are common and cause extensive morbidity; however, the value of
      treatment is under-appreciated. Many procedures allow the treatment of varicose
      veins with minimal cost and extensive literature supporting differing minimally
      invasive approaches. In this article, we investigate the current literature
      regarding treatment options, clinical outcome and the cost-benefit economics
      associated with varicose vein treatment. The practice of defining clinical
      outcome with quality of life (QOL) assessment is explained to provide valid
      concepts of treatment success beyond occlusion rates. 

PMID- 24091793
TI  - Fruit and vegetable intake and breast cancer risk defined by estrogen and
      progesterone receptor status: the Japan Public Health Center-based Prospective
      Study.
AB  - BACKGROUND: Epidemiological evidence for the impact of fruit and vegetable intake
      on breast cancer risk among the Japanese populations is scarce. OBJECTIVE: The
      purpose of this study was to evaluate the association between fruit and vegetable
      intake and breast cancer risk among 47,289 Japanese women. DESIGN: The study was
      conducted under a population-based prospective cohort design. Dietary assessment
      was performed using a validated food frequency questionnaire. A Cox proportional
      hazards regression model was used to calculate relative risks (RRs) and their
      corresponding 95 % confidence intervals (CIs). RESULTS: During an average of 10.2
      years of follow-up, 452 cases of breast cancer were newly diagnosed. No
      association with breast cancer risk was seen for intake of total fruits and
      vegetables, cruciferous vegetables, green-leaf vegetables, yellow vegetables, or
      tomato products in overall or postmenopausal women. Cruciferous vegetable intake
      was associated with a statistically significant decrease in risk of premenopausal
      breast cancer [multivariable-RRQ4 vs. Q1 = 0.64 (95 % CI = 0.38-1.10; p trend =
      .046)] and showed a marginally inverse association with ER+ PR+ tumors [RRper 100
      g increment = 0.64 (95 % CI = 0.41-1.00)]. In contrast, positive associations
      were seen between intake of total fruits and citrus fruits and breast cancer risk
      in overall and premenopausal women. However, these associations for fruit were
      all attenuated with additional adjustment for vitamin C intake. CONCLUSIONS: Our
      results suggest an overall null association between total fruit and vegetable
      intake and breast cancer risk. Intake of cruciferous vegetable showed a
      statistically significant association with a decreased risk of breast cancer
      among premenopausal women.

PMID- 24091794
TI  - Racial disparities in red meat and poultry intake and breast cancer risk.
AB  - PURPOSE: Research on the role of red meat and poultry consumption in breast
      carcinogenesis is inconclusive, but the evidence in African-American (AA) women
      is lacking. The association between consuming meat and breast cancer risk was
      examined in the Women's Circle of Health Study involving 803 AA cases, 889 AA
      controls, 755 Caucasian cases, and 701 Caucasian controls. METHODS: Dietary
      information was collected using a Food Frequency Questionnaire. Odds ratios (OR)
      and 95 % confidence intervals (CI) were obtained from logistic regression models
      adjusting for potential covariates. RESULTS: Comparing the fourth versus the
      first quartiles, among Caucasian women, processed meat (OR = 1.48; 95 % CI 1.07
      2.04), unprocessed red meat (OR = 1.40; 95 % CI 1.01-1.94), and poultry intakes
      (OR = 1.42; 95 % CI 1.01-1.99) increased breast cancer risk. Risk associated with
      poultry intake was more dominant in premenopausal women (OR = 2.33; 95 % CI 1.44
      3.77) and for women with ER- tumors (OR = 2.55; 95 % CI 1.29-5.03) in the
      Caucasian group. Associations in AA women were mostly null except for a
      significant increased risk trend with processed meat consumption for ER+ tumors
      (OR = 1.36; 95 % CI 0.94-1.97, p trend = 0.04). CONCLUSIONS: Overall,
      associations between breast cancer risk and consumption of red meat and poultry
      were of different magnitude in AA and Caucasian women, with further differences
      noted by menopausal and hormone receptor status in Caucasian women. This is the
      first study to examine racial differences in meat and breast cancer risk and
      represents some of the first evidence in AA women.

PMID- 24091795
TI  - Expression of alpha-taxilin in the murine gastrointestinal tract: potential
      implication in cell proliferation.
AB  - alpha-Taxilin, a binding partner of the syntaxin family, is a candidate tumor
      marker. To gain insight into the physiological role of alpha-taxilin in normal
      tissues, we examined alpha-taxilin expression by Western blot and performed
      immunochemical analysis in the murine gastrointestinal tract where cell renewal
      vigorously occurs. alpha-Taxilin was expressed in the majority of the
      gastrointestinal tract and was prominently expressed in epithelial cells positive
      for Ki-67, a marker of actively proliferating cells. In the small intestine,
      alpha-taxilin was expressed in transient-amplifying cells and crypt base columnar
      cells intercalated among Paneth cells. In the corpus and antrum of the stomach,
      alpha-taxilin was expressed in cells localized in the lower pit and at the gland,
      respectively, but not in parietal or zymogenic cells. During development of the
      small intestine, alpha-taxilin was expressed in Ki-67-positive regions.
      Inhibition of cell proliferation by suppression of the Notch cascade using a
      gamma-secretase inhibitor led to a decrease in alpha-taxilin- and Ki-67-positive
      cells in the stomach. These results suggest that expression of alpha-taxilin is
      regulated in parallel with cell proliferation in the murine gastrointestinal
      tract. 

PMID- 24091798
TI  - Magnetic, high-field EPR studies and catalytic activity of Schiff base
      tetranuclear CuII2FeIII2 complexes obtained by direct synthesis.
AB  - Two novel heterometallic complexes [Cu2Fe2(HL(1))2(H2L(1))2].10DMSO (1) and
      [Cu2Fe2(HL(2))2(H2L(2))2].2DMF (2) have been prepared using the open-air reaction
      of copper powder, iron(II) chloride and DMSO (1) or DMF (2) solutions of the
      polydentate Schiff base (H4L(1), 1; H4L(2), 2) formed in situ from
      salicylaldehyde (1) or 5-bromo-salicylaldehyde (2) and
      tris(hydroxymethyl)aminomethane. Crystallographic analysis revealed that both
      compounds are based on the centrosymmetric tetranuclear core {Cu(II)2Fe(III)2(MU
      O)6} where metal centres are joined by MU-O bridges from the deprotonated ligands
      forming a nonlinear chain-like arrangement. Variable-temperature (1.8-300 K)
      magnetic susceptibility measurements of 1 and 2 showed a decrease of the
      effective magnetic moment value at low temperature, indicative of
      antiferromagnetic coupling (JCu-Fe/hc = -10.2 cm(-1), JFe-Fe/hc = -10.5 cm(-1) in
      1, JCu-Fe/hc = -10.5 cm(-1), JFe-Fe/hc = -8.93 cm(-1) in 2) between the magnetic
      centres in both compounds. They reveal an exceptionally high catalytic activity
      in the oxidation of cyclohexane with hydrogen peroxide under mild conditions,
      with the best observed yield/TON combined values of 36%/596 and 44%/1.1 * 10(3)
      for 1 and 2, respectively.

PMID- 24091797
TI  - Analysis of nuclear actin by overexpression of wild-type and actin mutant
      proteins.
AB  - Compared to the cytoplasmic F-actin abundance in cells, nuclear F-actin levels
      are generally quite low. However, nuclear actin is present in certain cell types
      including oocytes and under certain cellular conditions including stress or serum
      stimulation. Currently, the architecture and polymerization status of nuclear
      actin networks has not been analyzed in great detail. In this study, we
      investigated the architecture and functions of such nuclear actin networks. We
      generated nuclear actin polymers by overexpression of actin proteins fused to a
      nuclear localization signal (NLS). Raising nuclear abundance of a NLS wild-type
      actin, we observed phalloidin- and LifeAct-positive actin bundles forming a
      nuclear cytoskeletal network consisting of curved F-actin. In contrast, a polymer
      stabilizing actin mutant (NLS-G15S-actin) deficient in interacting with the actin
      binding protein cofilin generated a nuclear actin network reminiscent of straight
      stress fiber-like microfilaments in the cytoplasm. We provide a first electron
      microscopic description of such nuclear actin polymers suggesting bundling of
      actin filaments. Employing different cell types from various species including
      neurons, we show that the morphology of and potential to generate nuclear actin
      are conserved. Finally, we demonstrate that nuclear actin affects cell function
      including morphology, serum response factor-mediated gene expression, and herpes
      simplex virus infection. Our data suggest that actin is able to form filamentous
      structures inside the nucleus, which share architectural and functional
      similarities with the cytoplasmic F-actin. 

PMID- 24091796
TI  - Posttranslational modifications of desmin and their implication in biological
      processes and pathologies.
AB  - Desmin, the muscle-specific intermediate filament, is involved in myofibrillar
      myopathies, dilated cardiomyopathy and muscle wasting. Desmin is the target of
      posttranslational modifications (PTMs) such as phosphorylation, ADP-ribosylation
      and ubiquitylation as well as nonenzymatic modifications such as glycation,
      oxidation and nitration. Several PTM target residues and their corresponding
      modifying enzymes have been discovered in human and nonhuman desmin. The major
      effect of phosphorylation and ADP-ribosylation is the disassembly of desmin
      filaments, while ubiquitylation of desmin leads to its degradation. The
      regulation of the desmin filament network by phosphorylation and ADP-ribosylation
      was found to be implicated in several major biological processes such as
      myogenesis, myoblast fusion, muscle contraction, muscle atrophy, cell division
      and possibly desmin interactions with its binding partners. Phosphorylation of
      desmin is also implicated in many forms of desmin-related myopathies
      (desminopathies). In this review, we summarize the findings on desmin PTMs and
      their implication in biological processes and pathologies, and discuss the
      current knowledge on the regulation of the desmin network by PTMs. We conclude
      that the desmin filament network can be seen as an intricate scaffold for muscle
      cell structure and biological processes and that its dynamics can be affected by
      PTMs. There are now precise tools to investigate PTMs and visualize cellular
      structures that have been underexploited in the study of desminopathies. Future
      studies should focus on these aspects. 

PMID- 24091799
TI  - Genetic medicine and incidental findings: it is more complicated than deciding
      whether to disclose or not.
AB  - PURPOSE: The aim of this study was to explore the clinical management of
      incidental findings. Advances in the speed and sensitivity of genetic
      technologies have not only improved the diagnostic rate but also result in an
      increase in unanticipated diagnoses. Recent debate on such "incidental findings"
      has considered whether or not to actively search for and, then, disclose
      incidental findings. In our experience, many incidental findings need to be
      investigated in family members before their clinical significance can be
      assessed. This adds complexity to the debate about disclosure. METHODS: Using
      anonymized clinical examples, we illustrate the downstream implications when a
      result reveals an incidental abnormality of potential clinical significance that
      is not related to the reasons for doing the test. RESULTS: Our examples
      illustrate that the determination of clinical significance may require
      participation of family members in both testing and surveillance. CONCLUSION: The
      need to investigate multiple relatives in order to decide whether or not a
      finding is clinically significant has implications for consent and disclosure
      practices. Communication with, and care for, relatives who have no reason to
      suspect particular diagnoses is a challenge for any health-care service. These
      costs also need to be taken into account as genetic testing enters mainstream
      medicine.

PMID- 24091800
TI  - Communication of genetic test results to family and health-care providers
      following disclosure of research results.
AB  - PURPOSE: Few studies have examined methods to promote communication following the
      return of DNA mismatch repair genetic test results obtained during research. The
      purpose of the present study was to evaluate a telephone protocol for returning
      research results of DNA mismatch repair gene testing to identify Lynch syndrome.
      METHODS: We invited individuals with known DNA mismatch repair mutations in their
      family, who were enrolled in the Colon Cancer Family Registry at the Mayo Clinic,
      to participate in this study. Participants completed surveys before and 6 months
      after DNA mismatch repair test result disclosure. RESULTS: Among 107
      participants, 79% opted to learn their DNA mismatch repair test results; of
      these, 44 (41%) carried DNA mismatch repair mutations. After disclosure, 54%
      reported screening for any type of cancer. Among carriers, >74% reported
      communicating results to family; communication was predicted by baseline
      confidence in coping with the genetic test result (Z = 1.97; P = 0.04). Result
      disclosure to a physician was predicted by greater perceived cancer risk (Z =
      2.08; P = 0.03) and greater intention to share results with family (Z = 3.07; P =
      0.002). CONCLUSION: Research versus clinically based gene disclosure presents
      challenges. A telephone disclosure process for the return of research-based
      results among Lynch syndrome families led to high rates of result uptake and
      participant communication of results to providers and family members.

PMID- 24091801
TI  - Maternal plasma DNA testing for aneuploidy in pregnancies achieved by assisted
      reproductive technologies.
AB  - PURPOSE: We sought to compare measurements of circulating cell-free DNA as well
      as Down syndrome test results in women with naturally conceived pregnancies with
      those conceived using assisted reproductive technologies. METHODS: Data regarding
      assisted reproductive technologies were readily available from seven enrollment
      sites participating in an external clinical validation trial of nested
      case/control design. Measurements of circulating cell-free fetal and total DNA,
      fetal fraction (ratio of fetal to total DNA), chromosome-specific z-scores, and
      karyotype results were available for analysis. RESULTS: Analyses were restricted
      to 632 euploid (5.2% assisted reproductive technologies) and 73 Down syndrome
      (13.7% assisted reproductive technologies), including 16 twin pregnancies. No
      differences were found for fetal or total circulating cell-free DNA, or for the
      fetal fraction in euploid (P = 0.70) or Down syndrome (P = 0.58) pregnancies by
      method of conception. There appeared to be systematic z-score reductions for
      chromosomes 21, 18, and 13 in assisted reproductive technologies versus natural
      euploid pregnancies (P = 0.048, 0.0032, and 0.36, respectively). CONCLUSION:
      Assisted reproductive technologies and naturally conceived pregnancies contribute
      similar levels of circulating cell-free DNA into maternal circulation. Small
      differences in the z-scores of pregnancies achieved by assisted reproductive
      technologies were observed and do not appear to be test-related artifacts.
      However, the findings need confirmation before any consideration of changes to
      testing and reporting protocols.

PMID- 24091802
TI  - "I prefer a child with ...": designer babies, another controversial patent in the
      arena of direct-to-consumer genomics.

PMID- 24091803
TI  - Stability-Indicating Spectrofluorimetric Methods for the Determination of
      Metolazone and Xipamide in Their Tablets. Application to Content Uniformity
      Testing.
AB  - A highly sensitive, simple and rapid stability-indicating spectrofluorimetric
      method was developed for the determination of metolazone (MET) and xipamide (XPM)
      in their tablets. The proposed method is based on the measurement of the native
      fluorescence of MET in methanol at 437 nm after excitation at 238 nm and XPM in
      alkaline methanolic solution at 400 nm after excitation at 255 nm. The
      fluorescence-concentration plots were rectilinear over the range of 2.0- 20.0
      ng/mL for MET and 0.2- 2.0 MUg/mL for XPM, with lower detection limits (LOD) of
      0.35 ng/mL and 0.02 MUg/mL and a lower quantification limit (LOQ) of 1.05 ng/mL
      and 0.07 MUg/mL for MET and XPM, respectively. The method was successfully
      applied to the analysis of MET and XPM in their commercial tablets and the
      results were in good agreement with those obtained using the official and
      comparison methods, respectively. Furthermore, content uniformity testing of the
      studied pharmaceutical tablets was also conducted. The application of the
      proposed method was extended to stability studies of MET and XPM after exposure
      to different forced degradation conditions, such as acidic, alkaline, oxidative
      and photolytic degradation conditions, according to ICH Guidelines. Moreover, the
      method was utilized to investigate the kinetics of the alkaline, acidic and
      photolytic degradation of MET. The apparent first-order rate constants and half
      life times were calculated. Proposals for the degradation pathways for both MET
      and XPM were postulated. 

PMID- 24091804
TI  - Fluorescence Turn on Sensor for Sulfate Ion in Aqueous Medium Using Tripodal
      Cu(2+) Ensemble.
AB  - We report the selective recognition of sulfate anion in aqueous medium at
      biological pH 7.2 over the other interfering anions based on naphthoic acid
      bearing tripodal ligand by applying fluorescence turn off -on mechanism. The
      carboxylic acid groups in the ligand enhance the solubility in water and enable
      it to form complex with copper salt. Thus formed L-Cu2+ ensemble quench the
      fluorescence of the parent ligand and in turn recognize sulfate anion via revival
      of fluorescence intensity. The 1:2 stoichiometry was confirmed by ESI mass
      spectral data and Job's plot. The average binding constant was found to be
      6.2*10(8) M(-2).

PMID- 24091805
TI  - Structures and Luminescent Properties of Two 2D Coordination Polymers Containing
      Tb(III) or Dy(III) Ions.
AB  - Two 2D rare earth terbium and dysprosium coordination polymers with 2,4
      pyridinedicarboxylate and oxalate anions have been synthesized by hydrothermal
      method, the formula is {[RE(pda)(ox)0.5(H2O)4].2H2O}n (RE = Tb (1) and Dy (2);
      H2pda = 2,4-pyridinedicarboxylic acid; ox = oxalate anion). The two complexes are
      isomorphic and crystallized in monoclinic system, P21/c space group. Each pda
      anion connects two rare earth ions with 2- carboxyl group and the nitrogen atom
      but the 4- carboxyl group does not coordinate with rare earth ions. Each ox anion
      connects two rare earth ions by MU 2-bridge way. Both the complexes exhibit
      intense characteristic luminescence of Tb(III) or Dy(III) ion with excitation of
      UV-rays. 

PMID- 24091806
TI  - Antibiotic prescribing to adults with sore throat in the United States, 1997
      2010.

PMID- 24091807
TI  - Cardiac metaiodobenzylguanidine imaging and heart failure.
AB  - The autonomic nervous system has pivotal roles in pathophysiology and prognosis
      in patients with heart failure. Cardiac (123)I-labeled metaiodobenzylguanidine
      (MIBG) imaging enables noninvasive and quantitative assessment of cardiac
      sympathetic innervation in cardiology practice. Several investigations have
      demonstrated independent and incremental prognostic values of this imaging
      technique in combination with clinical information in patients with heart
      failure. Cardiac MIBG imaging may help cardiologists evaluate cardiac sympathetic
      nerve function and predict lethal event risk in heart failure. It can contribute
      not only to the identification of low-risk or high-risk probability for lethal
      events but also to the selection of the appropriate therapeutic strategy, such as
      medical and device therapy in patients at greater risk for lethal outcomes due to
      pump failure or sudden arrhythmic events. Thus, precise risk stratification
      through cardiac MIBG imaging may contribute to more effective use of medical
      resources and more appropriate selection of therapeutic strategy in heart failure
      patients. 

PMID- 24091809
TI  - Hyperosteoidosis and hypermineralization in the same bone: bone tissue analyses
      in a boy with a homozygous BMP1 mutation.
AB  - Recently, homozygous mutations in BMP1 were identified as a cause of bone
      fragility in children with high areal bone mineral density. We examined iliac
      bone tissue from a 12-year-old boy with a homozygous mutation that leads to a
      p.Gly12Arg change in the signal peptide of BMP1, an enzyme that cleaves C
      propeptide off the procollagen type I molecule. Histomorphometric analyses
      revealed marked hyperosteoidosis, with osteoid volume per bone volume at
      approximately 11 SD above the mean value for controls. At the same time,
      quantitative backscattered electron imaging showed drastic hypermineralization of
      mineralized bone matrix. CaPeak, representing the most frequently observed
      calcium content of mineralized matrix in trabecular bone, was 9 SD above the mean
      for the control population, corresponding to a 21 % higher calcium content in the
      patient specimen than in the average control sample. These results are similar to
      those that were previously reported in an individual who had a mutation in the C
      propeptide cleavage site of procollagen type I. It thus appears that disturbed C
      propeptide cleavage impairs mineralization in two ways: first, the onset of
      mineralization is delayed, leading to an increased amount of unmineralized
      osteoid, and second, once mineralization starts, too much mineral is incorporated
      into the bone matrix, resulting in hypermineralization.

PMID- 24091808
TI  - Heart failure in very old adults.
AB  - Heart failure (HF) increases significantly in relation to advancing age, yet
      management for HF in very old adults remains ambiguous. With aging, not only do
      age-related, morphological and physiological cardiovascular changes predispose to
      HF, there is also increased prevalence of comorbid conditions that compound
      cardiac limitations (e.g., renal insufficiency and chronic obstructive lung
      disease) and others that tend to overwhelm limited cardiovascular reserves (e.g.,
      infections and ischemia). Standard HF pharmacological and device therapies do
      little to moderate the wide spectrum of insidious age-related processes that are
      elemental to HF pathophysiology among older patients. Moreover, the utility of
      standard HF therapy is usually premised on its efficacy for life prolongation,
      whereas quality of life, increased physical and cognitive function, and preserved
      independence may be regarded as higher (or even highest) priority. In this review
      we study age-related susceptibility to HF, as well as the utility and limitations
      of standard HF strategies. Both HF with reduced ejection fraction and HF with
      preserved ejection fraction are considered. 

PMID- 24091810
TI  - Relationship between alveolar nitric oxide concentration in exhaled air and small
      airway function in COPD.
AB  - Nitrative stress is thought to be involved in the inflammatory process in COPD
      airways, and the alveolar nitric oxide concentration (CAlv) has been reported to
      be increased. However, the CAlv levels are also regulated by gas diffusion at
      alveolar sites. The aim of the study was to assess the relationship between the
      CAlv and pulmonary function in COPD patients, while taking into account the lung
      diffusion capacity. Twenty stable COPD patients (GOLD stage1/2/3/4 = 6/8/6/0) and
      16 healthy subjects took part in this cross-sectional study. Fractional exhaled
      nitric oxide (FE(NO)), CAlv, and pulmonary functions were measured. Pulmonary
      function, including single nitrogen washout curve (dN2) and diffusion capacity
      for carbon monoxide (DL(CO)), was also evaluated in patients with COPD. The mean
      FE(NO) levels (20.7 ppb versus 16.3 ppb, p < 0.05) and the mean CAlv levels (6.4
      ppb versus 4.2 ppb, p < 0.01) in COPD patients were significantly increased
      compared to those in HS. The CAlv level in COPD was significantly correlated with
      dN2, %DL(CO)/alveolar volume (VA). Using the standard entry method of
      multivariate analysis to adjust for dN2 and %DL(CO)/VA, dN2 (beta = 0.54, p =
      0.005) and %DL(CO)/VA (beta = -0.44, p = 0.018) still showed significant
      correlations with the CAlv levels. These results suggest that the CAlv could be a
      useful marker for the small airway dysfunction in COPD. Airway inflammation,
      including excess nitric oxide generation in the peripheral airways, might be
      related to the pathophysiology of COPD.

PMID- 24091812
TI  - Whole-slide imaging and automated image analysis: considerations and
      opportunities in the practice of pathology.
AB  - Digital pathology, the practice of pathology using digitized images of pathologic
      specimens, has been transformed in recent years by the development of whole-slide
      imaging systems, which allow for the evaluation and interpretation of digital
      images of entire histologic sections. Applications of whole-slide imaging include
      rapid transmission of pathologic data for consultations and collaborations,
      standardization and distribution of pathologic materials for education, tissue
      specimen archiving, and image analysis of histologic specimens. Histologic image
      analysis allows for the acquisition of objective measurements of
      histomorphologic, histochemical, and immunohistochemical properties of tissue
      sections, increasing both the quantity and quality of data obtained from
      histologic assessments. Currently, numerous histologic image analysis software
      solutions are commercially available. Choosing the appropriate solution is
      dependent on considerations of the investigative question, computer programming
      and image analysis expertise, and cost. However, all studies using histologic
      image analysis require careful consideration of preanalytical variables, such as
      tissue collection, fixation, and processing, and experimental design, including
      sample selection, controls, reference standards, and the variables being
      measured. The fields of digital pathology and histologic image analysis are
      continuing to evolve, and their potential impact on pathology is still growing.
      These methodologies will increasingly transform the practice of pathology,
      allowing it to mature toward a quantitative science. However, this maturation
      requires pathologists to be at the forefront of the process, ensuring their
      appropriate application and the validity of their results. Therefore, histologic
      image analysis and the field of pathology should co-evolve, creating a symbiotic
      relationship that results in high-quality reproducible, objective data. 

PMID- 24091811
TI  - Tumor microenvironment regulates metastasis and metastasis genes of mouse MMTV
      PymT mammary cancer cells in vivo.
AB  - Metastasis is the primary cause of death in breast cancer patients, yet there are
      challenges to modeling this process in vivo. The goal of this study was to
      analyze the effects of injection site on tumor growth and metastasis and gene
      expression of breast cancer cells in vivo using the MMTV-PymT breast cancer model
      (Met-1 cells). Met-1 cells were injected into 5 sites (subcutaneous, mammary fat
      pad, tail vein, intracardiac, and intratibial), and tumors and metastases were
      monitored using bioluminescent imaging and confirmed with gross necropsy and
      histopathology. Met-1 tumors were analyzed based on morphology and changes in
      gene expression in each tissue microenvironment. There were 6 permissible sites
      of Met-1 tumor growth (mammary gland, subcutis, lung, adrenal gland, ovary,
      bone). Met-1 cells grew faster in the subcutis compared to mammary fat pad tumors
      (highest Ki-67 index). Morphologic differences were evident in each tumor
      microenvironment. Finally, 7 genes were differentially expressed in the Met-1
      tumors in the 6 sites of growth or metastasis. This investigation demonstrates
      that breast cancer progression and metastasis are regulated by not only the tumor
      cells but also the experimental model and unique molecular signals from the tumor
      microenvironment. 

PMID- 24091813
TI  - Fatty liver hemorrhagic syndrome in the backyard chicken: a retrospective
      histopathologic case series.
AB  - Fatty liver hemorrhagic syndrome, characterized by sudden death in
      overconditioned hens due to hepatic rupture and hemorrhage, is one of the leading
      noninfectious idiopathic causes of mortality in backyard chickens. Nutritional,
      genetic, environmental, and hormonal factors, or combinations of these, have been
      proposed yet not proven as the underlying cause. In an attempt to characterize
      the hepatic changes leading to the syndrome, this retrospective case study
      examined 76 backyard chickens that were diagnosed with fatty liver hemorrhagic
      syndrome between January 2007 and September 2012 and presented for necropsy to
      the diagnostic laboratory of the California Animal Health and Food Safety
      Laboratory System. A majority of the birds were female (99%), obese (97.5%), and
      in active lay (69.7%). Livers were examined histologically, and the degree of
      hepatocellular vacuolation (lipidosis), the reticular stromal architecture, the
      presence of collagenous connective tissue, and vascular wall changes were
      evaluated and graded using hematoxylin and eosin, Gomori's reticulin, oil red O,
      Masson's trichrome, and Verhoeff-Van Gieson stains. Interestingly, there was no
      correlation between lipidosis and reticulin grades; hepatocellular lipidosis was
      absent in 22% of the cases and mild in 26% of the cases. Additionally, there was
      evidence of repeated bouts of intraparenchymal hemorrhage before the acute "bleed
      out" in 35.5% of the cases. These data are not supportive of the previously
      proposed causes and provide a framework for future studies to elucidate the
      pathogenesis of this condition. Furthermore, the data shown in this study support
      hemorrhagic liver syndrome as a more accurate name, as hepatic lipidosis is
      absent in a significant proportion of ruptured livers. 

PMID- 24091814
TI  - Safety biomarkers in preclinical development: translational potential.
AB  - The identification, application, and qualification of safety biomarkers are
      becoming increasingly critical to successful drug discovery and development as
      companies are striving to develop drugs for difficult targets and for novel
      disease indications in a risk-adverse environment. Translational safety
      biomarkers that are minimally invasive and monitor drug-induced toxicity during
      human clinical trials are urgently needed to assess whether toxicities observed
      in preclinical toxicology studies are relevant to humans at therapeutic doses.
      The interpretation of data during the biomarker qualification phase should
      include careful consideration of the analytic method used, the biology,
      pharmacokinetic and pharmacodynamic properties of the biomarker, and the
      pathophysiology of the process studied. The purpose of this review is to
      summarize commonly employed technologies in the development of fluid- and tissue
      based safety biomarkers in drug discovery and development and to highlight areas
      of ongoing novel assay development. 

PMID- 24091815
TI  - N-cadherin expression in feline mammary tumors is associated with a reduced E
      cadherin expression and the presence of regional metastasis.
AB  - The cadherin family of adhesion molecules regulates cell-cell interactions. N
      cadherin is expressed by neural and fibroblast cells but not by normal epithelial
      cells. In human medicine, the role of N-cadherin in breast cancer remains
      controversial, but some studies have described the switch from E-cadherin to N
      cadherin as a critical step in the malignant progression of neoplastic cells. The
      present study was carried out on 160 feline mammary tumors (21 adenomas and 139
      carcinomas). The relationship between the immunohistochemical expression of N
      cadherin in neoplastic epithelial cells and 2 established prognostic factors such
      as regional metastasis and tumor grade was examined. The results of the study
      showed a statistically significant relation between the expression of N-cadherin
      and the 2 prognostic factors, and also a reduced expression of E-cadherin in
      tumors that expressed N-cadherin. 

PMID- 24091816
TI  - Phenotype and regulation of immunosuppressive Vdelta2-expressing gammadelta T
      cells.
AB  - The proliferation and interleukin-2 production of CD4(+)CD25(-) alphabeta T cells
      were inhibited in a cell-contact manner by Vdelta2 gammadelta T cells. The
      transcription factor Helios was constitutively expressed in about one-third of
      circulating gammadelta T cells and was upregulated by CD28-signaling. Our data
      suggest that Helios could serve as a marker for differential activation status
      rather than for regulatory T cells (Treg). Our findings also indicate that the
      interaction of CD86 on activated Vdelta2 T cells and cytotoxic T lymphocyte
      associated antigen-4 (CTLA-4) on activated alphabeta T cells mediated the
      suppression because the suppressive effect was abolished by blocking the
      CD86:CTLA-4 interaction. Pre-treatment of Vdelta2 T cells with Toll-like receptor
      2 ligands enhanced phosphorylation of MAPKs, Akt, and NF-kappaB and partially
      abrogated the suppressive capacity, whereas on co-cultured responder T cells
      inhibitory molecules were downregulated and Akt and NF-kappaB phosphorylation was
      restored. Our results suggest that the regulation of alphabeta T cell
      proliferation by activated Vdelta2 T cells might contribute to fine-tuning of
      alphabeta T cell responses.

PMID- 24091819
TI  - Drosophila chemotaxis: a first look with neurogenetics.
AB  - Chemotaxis, the ability to direct movements according to chemical cues in the
      environment, is important for the survival of most organisms. In our original
      article, we combined a quantitative behavioral assay with genetic manipulations
      to dissect the neural substrate for chemotaxis. In this Extra View article, we
      offer a more chronological narration of the findings leading to our key
      conclusion that aversion engages specific motor-related circuits and kinematics.
      We speculate on the separation and crosstalk between aversion and attraction
      circuits in the brain and the ventral nerve cord, and the implication for valence
      encoding in the olfactory system. 

PMID- 24091817
TI  - Switch from protective to adverse inflammation during influenza: viral
      determinants and hemostasis are caught as culprits.
AB  - Influenza viruses cause acute respiratory infections, which are highly contagious
      and occur as seasonal epidemic and sporadic pandemic outbreaks. Innate immune
      response is activated shortly after infection with influenza A viruses (IAV),
      affording effective protection of the host. However, this response should be
      tightly regulated, as insufficient inflammation may result in virus escape from
      immunosurveillance. In contrast, excessive inflammation may result in bystander
      lung tissue damage, loss of respiratory capacity, and deterioration of the
      clinical outcome of IAV infections. In this review, we give a comprehensive
      overview of the innate immune response to IAV infection and summarize the most
      important findings on how the host can inappropriately respond to influenza. 

PMID- 24091820
TI  - Conserved mechanisms for germ cell-specific localization of nanos3 transcripts in
      teleost species with aquaculture significance.
AB  - The importance of the aquaculture production is increasing with the declining
      global fish stocks, but early sexual maturation in several farmed species reduces
      muscle growth and quality, and escapees could have a negative impact on wild
      populations. A possible solution to these problems is the production of sterile
      fish by ablation of the embryonic primordial germ cells (PGCs), a technique
      developed in zebrafish. Cell-specific regulation of mRNA stability is crucial for
      proper specification of the germ cell lineage and commonly involves microRNA
      (miRNA)-mediated degradation of targeted mRNAs in somatic cells. This study
      reports on the functional roles of conserved motifs in the 3' untranslated region
      (UTR) of the miRNA target gene nanos3 identified in Atlantic cod, Atlantic
      salmon, and zebrafish. The 3'UTR of cod nanos3 was sufficient for targeting the
      expression of green fluorescent protein (GFP) to the presumptive PGCs in injected
      embryos of the three phylogenetically distant species. 3'UTR elements of
      importance for PGC-specific expression were further examined by fusing truncated
      3'UTR variants of cod nanos3 to GFP followed by injections in zebrafish embryos.
      The expression patterns of the GFP constructs in PGCs and somatic cells suggested
      that the proximal U-rich region is responsible for the PGC-specific stabilization
      of the endogenous nanos3 mRNA. Morpholino-mediated downregulation of the RNA
      binding protein Dead end (DnD), a PGC-specific inhibitor of miRNA action,
      abolished the fluorescence of the PGCs in cod and zebrafish embryos, suggesting a
      conserved DnD-dependent mechanism for germ cell survival and migration. 

PMID- 24091821
TI  - Identification of hypoxia-regulated genes in the liver of common sole (Solea
      solea) fed different dietary lipid contents.
AB  - Coastal systems could be affected by hypoxic events brought about by global
      change. These areas are essential nursery habitats for several fish species
      including the common sole (Solea solea L.). Tolerance of fish to hypoxia depends
      on species and also on their physiological condition and nutritional status.
      Indeed, high dietary lipid content has been recently shown to negatively impact
      the resistance of sole to a severe hypoxic challenge. In order to study the
      molecular mechanisms involved in the early response to hypoxic stress, the
      present work examined the hepatic transcriptome in common sole fed diets with low
      and high lipid content, exposed to severe hypoxia. The activity of AMP-activated
      protein kinase (AMPK) was also investigated through the quantification of
      threonine-172 phosphorylation in the alpha subunit. The results show that hypoxia
      consistently regulates several actors involved in energy metabolism pathways and
      particularly AMPKalpha, as well as some involved in cell growth and maintenance
      or unfolded protein response. Our findings reveal that (1) the expression of
      genes involved in biological processes with high energy cost or implicated in
      aerobic ATP synthesis was down-regulated by hypoxia, contrary to genes involved
      in neoglucogenesis or in angiogenesis, (2) the consumption of high lipid induced
      regulation of metabolic pathways going against this energy saving, and (3) this
      control was fine-tuned by the regulation of several transcriptomic factors. These
      results provide insight into the biological processes involved in the hepatic
      response to hypoxic stress and underline the negative impact of high lipid
      consumption on the tolerance of common sole to hypoxia. 

PMID- 24091822
TI  - Posterior fixation of thoracolumbar burst fractures: is it possible to protect
      one segment in the lumbar region?
AB  - BACKGROUND: The treatment for thoracolumbar burst fractures is controversial. The
      aim of this retrospective study was to compare intermediate-segment (IS) and long
      segment (LS) instrumentation in the treatment for these fractures. METHODS: IS
      instrumentation was considered as pedicle fixation two levels above and one level
      below the fractured vertebra (infra-laminar hooks attached to lower vertebra with
      pedicle screws). LS instrumentation was done two levels above and two levels
      below the fractured vertebra. Among a total of 25 consecutive patients, Group 1
      included ten patients treated by IS pedicle fixation, whereas Group 2 included
      fifteen patients treated by LS instrumentation. RESULTS: The measurements of
      local kyphosis (p = 0.955), sagittal index (p = 0.128), anterior vertebral height
      compression (p = 0.230) and canal diameter expansion (p = 0.839) demonstrated
      similar improvement at the final follow-up between the two groups. However, there
      was a significant difference (p < 0.05) between Group 1 and Group 2 regarding
      clinical outcome [Hannover scoring system, Oswestry disability questionnaire and
      the range of motion of the lumbar region compared to neutral (0 degrees )].
      CONCLUSIONS: The radiographic parameters were the same between the two groups.
      However, the clinical parameters demonstrated that IS instrumentation is a more
      effective management of thoracolumbar burst fractures.

PMID- 24091823
TI  - Angiographic evaluation of arterial configuration after acute tibial shortening.
AB  - INTRODUCTION: Tibial nonunion with bone and soft tissue loss is a challenging
      orthopedic problem. Acute tibial shortening is a well-defined technique; however,
      arterial configuration following acute tibial shortening has not been
      demonstrated by a clinical study. MATERIALS AND METHODS: Sixteen patients with
      tibial nonunion and one patient with acute tibial fracture accompanied by bone
      and soft tissue loss were treated by acute shortening followed by compression or
      relengthening between 2004 and 2010. Circulation was monitored by intraoperative
      Doppler ultrasound and hallux pulse oximetry. Arterial configuration was examined
      by digital subtraction angiography at the seventh postoperative day and by CT
      angiography at the second year. Bone healing and functional results were
      evaluated according to Paley's classification, and complications were evaluated
      according to Dahl's classification. RESULTS: Mean amount of bone loss was 3 +/-
      1.4 cm (range 1-6 cm); mean size of the soft tissue defects was 7 * 6.8 cm (range
      3 * 3 cm-10 * 10 cm). The mean follow-up period was 38 +/- 11.3 months (range 24
      57 months). The average amount of acute shortening was 5.4 +/- 1.6 cm (range 3-8
      cm). Average lengthening was 6 +/- 1.8 cm (range 4-8 cm), and the mean external
      fixation index was 1.4 months/cm (range 0.1-3.7 months). There was no detectable
      change in the arterial configuration of patients with acute shortening up to 4
      cm. Minimal arterial bending was observed in patients that 4-6 cm of shortening
      was performed. Arterial configuration of the patients that 8 cm acute shortening
      was performed showed increased tortuosity, but the patency was maintained.
      CONCLUSION: Acute shortening of tibia in nonunions with soft tissue defects
      allows for primary closure or reduces the need for grafting and secondary
      operations. Although the amount of acute shortening depends upon intraoperative
      assessment with Doppler ultrasound and hallux pulse oximetry, acute compression
      up to 8 cm can be attained in proximal tibia. More than 4 cm of acute shortening
      leads to increased tortuosity of major arteries rather than kinking, and this new
      arterial configuration is maintained for up to 2 years with no problem in
      circulation.

PMID- 24091824
TI  - Histological assessment of tissue from large human bone defects repaired with
      beta-tricalcium phosphate.
AB  - This report describes the histological characteristics of large human bone
      defects that were implanted with beta-tricalcium phosphate (beta-TCP). Samples
      were obtained longer after the primary operation than in the earlier studies. We
      assessed a total of nine biopsies taken 33-208 weeks after implantation. The
      tissue sections were stained with hematoxylin-eosin for general observation, with
      Gomori stain to visualize the reticulin fibers, and with an antibody against
      tartrate-resistant alkaline phosphatase (TRAP) to characterize the cells. Ongoing
      bone remodeling was observed even 208 weeks after implantation as determined by
      the presence of osteoclasts and active osteoblasts and new woven and lamellar
      bone. We observed multinuclear giant cells phagocytosing the biomaterial and the
      attachment of osteoclasts to the beta-TCP. The osteoclasts showed intense TRAP
      positivity, while the giant cells showed variable TRAP positivity. There was a
      zonal pattern in the original defects: The central regions showed granules and
      fibrous septa, while peripheral areas showed a layer of new bone formation. These
      data demonstrate ongoing bone remodeling long after implantation in the
      peripheral regions of the original defects as well as fibrous changes in the
      central regions and phagocytosis of biomaterial by multinuclear giant cells.

PMID- 24091825
TI  - Wafer-scale metasurface for total power absorption, local field enhancement and
      single molecule Raman spectroscopy.
AB  - The ability to detect molecules at low concentrations is highly desired for
      applications that range from basic science to healthcare. Considerable interest
      also exists for ultrathin materials with high optical absorption, e.g. for
      microbolometers and thermal emitters. Metal nanostructures present opportunities
      to achieve both purposes. Metal nanoparticles can generate gigantic field
      enhancements, sufficient for the Raman spectroscopy of single molecules. Thin
      layers containing metal nanostructures ("metasurfaces") can achieve near-total
      power absorption at visible and near-infrared wavelengths. Thus far, however,
      both aims (i.e. single molecule Raman and total power absorption) have only been
      achieved using metal nanostructures produced by techniques (high resolution
      lithography or colloidal synthesis) that are complex and/or difficult to
      implement over large areas. Here, we demonstrate a metasurface that achieves the
      near-perfect absorption of visible-wavelength light and enables the Raman
      spectroscopy of single molecules. Our metasurface is fabricated using thin film
      depositions, and is of unprecedented (wafer-scale) extent.

PMID- 24091826
TI  - A quest for supramolecular gelators: silver(I) complexes with quinoline-urea
      derivatives.
AB  - The quinoline urea derivatives 1,3-di(quinolin-5-yl)urea (DQ5U), 1-phenyl-3
      (quinolin-6-yl)urea (PQ6U), 1-(isoquinolin-5-yl)-3-phenylurea (PiQ5U) and 1
      phenyl-3-(3,5-bis(pyrid-2-yl)-1,2,4-triazol-4-yl)urea (PPT4U) have been
      synthesised and structurally characterized by powder and single crystal X-ray
      diffraction. Their gelator behaviour in the formation of Ag-complexes has been
      explored. Compound DQ5U proved capable of gelating the mixed solvent EtOH-DMF 1 :
      2 (v/v) when mixed with 1 equivalent of AgNO3. In the case of PQ6U, two
      polymorphic forms of the complex [Ag(PQ6U)2]NO3, plus the solvated form
      [Ag(PQ6U)2]NO3.CH3CN, were crystallized. Photophysical characterization of the
      ligands has been conducted in solution, while fluorescence microscopy has been
      used to examine the microstructure and photophysical properties of the gels
      formed by PQ5U and DQ5U with AgNO3. 

PMID- 24091827
TI  - An evaluation of the effects of acute and chronic L-tyrosine administration on
      BDNF levels and BDNF mRNA expression in the rat brain.
AB  - Tyrosinemia type II, which is also known as Richner-Hanhart syndrome, is an
      inborn error of metabolism that is due to a block in the transamination reaction
      that converts tyrosine to p-hydroxyphenylpyruvate. Because the mechanisms of
      neurological dysfunction in hypertyrosinemic patients are poorly known and the
      symptoms of these patients are related to the central nervous system, the present
      study evaluated brain-derived neurotrophic factor (BDNF) levels and bdnf mRNA
      expression in young rats and during growth. In our acute protocol, Wistar rats
      (10 and 30 days old) were killed 1 h after a single intraperitoneal L-tyrosine
      injection (500 mg/kg) or saline. Chronic administration consisted of L-tyrosine
      (500 mg/kg) or saline injections 12 h apart for 24 days in Wistar rats (7 days
      old), and the rats were killed 12 h after the last injection. The brains were
      rapidly removed, and we evaluated the BDNF levels and bdnf mRNA expression. The
      present results showed that the acute administration of L-tyrosine decreased both
      BDNF and bdnf mRNA levels in the striatum of 10-day-old rats. In the 30-day-old
      rats, we observed decreased BDNF levels without modifications in bdnf transcript
      level in the hippocampus and striatum. Chronic administration of L-tyrosine
      increased the BDNF levels in the striatum of rats during their growth, whereas
      bdnf mRNA expression was not altered. We hypothesize that oxidative stress can
      interact with the BDNF system to modulate synaptic plasticity and cognitive
      function. The present results enhance our knowledge of the pathophysiology of
      hypertyrosinemia.

PMID- 24091828
TI  - Potential effect of S-nitrosylated protein disulfide isomerase on mutant SOD1
      aggregation and neuronal cell death in amyotrophic lateral sclerosis.
AB  - Aggregation of misfolded protein and resultant intracellular inclusion body
      formation are common hallmarks of mutant superoxide dismutase (mSOD1)-linked
      familial amyotrophic lateral sclerosis (FALS) and have been associated with the
      selective neuronal death. Protein disulfide isomerase (PDI) represents a family
      of enzymatic chaperones that can fold nascent and aberrant proteins in the
      endoplasmic reticulum (ER) lumen. Recently, our group found that S-nitrosylated
      PDI could contribute to protein misfolding and subsequent neuronal cell death.
      However, the exact role of PDI in the pathogenesis of ALS remains unclear. In
      this study, we propose that PDI attenuates aggregation of mutant/misfolded SOD1
      and resultant neurotoxicity associated with ER stress. ER stress resulting in PDI
      dysfunction therefore provides a mechanistic link between deficits in molecular
      chaperones, accumulation of misfolded proteins, and neuronal death in
      neurodegenerative diseases. In contrast, S-nitrosylation of PDI inhibits its
      activity, increases mSOD1 aggregation, and increases neuronal cell death.
      Specifically, our data show that S-nitrosylation abrogates PDI-mediated
      attenuation of neuronal cell death triggered by thapsigargin. Biotin switch
      assays demonstrate S-nitrosylated PDI both in the spinal cords of SOD1 (G93A)
      mice and human patients with sporadic ALS. Therefore, denitrosylation of PDI may
      have therapeutic implications. Taken together, our results suggest a novel
      strategy involving PDI as a therapy to prevent mSOD1 aggregation and neuronal
      degeneration. Moreover, the data demonstrate that inactivation of PDI by S
      nitrosylation occurs in both mSOD1-linked and sporadic forms of ALS in humans as
      well as mice.

PMID- 24091830
TI  - First biological measurements of deep-sea corals from the Red Sea.
AB  - It is usually assumed that metabolic constraints restrict deep-sea corals to cold
      water habitats, with 'deep-sea' and 'cold-water' corals often used as synonymous.
      Here we report on the first measurements of biological characters of deep-sea
      corals from the central Red Sea, where they occur at temperatures exceeding 20
      degrees C in highly oligotrophic and oxygen-limited waters. Low respiration
      rates, low calcification rates, and minimized tissue cover indicate that a
      reduced metabolism is one of the key adaptations to prevailing environmental
      conditions. We investigated four sites and encountered six species of which at
      least two appear to be undescribed. One species is previously reported from the
      Red Sea but occurs in deep cold waters outside the Red Sea raising interesting
      questions about presumed environmental constraints for other deep-sea corals. Our
      findings suggest that the present understanding of deep-sea coral persistence and
      resilience needs to be revisited.

PMID- 24091829
TI  - E6AP in the brain: one protein, dual function, multiple diseases.
AB  - E6-Associated Protein (E6AP), the founding member of the HECT (Homologus to E6AP
      C terminus) family of ubiquitin ligases, has been gaining increased attention
      from the scientific community. In addition to its ubiquitin ligase function, our
      laboratory has also identified steroid hormone receptor transcriptional
      coactivation as yet another essential function of this protein. Furthermore, it
      has been established that E6AP has a role in numerous diseases including cancers
      and neurological syndromes. In this review, we delineate genetic and biochemical
      knowledge of E6AP and we focus on its role in the pathobiology of neuro
      developmental and neuro-aging diseases; bringing to light important gaps of
      knowledge related to the involvement of its well-studied ligase function versus
      the much less studied nuclear receptor transcriptional coactivation function in
      the pathogenesis of these diseases. Tackling these gaps of knowledge could reveal
      novel possible neuro-pathobiological mechanisms and present crucial information
      for the design of effective treatment modalities for devastating CNS diseases.

PMID- 24091831
TI  - Molecular classification of myeloproliferative neoplasms-pros and cons.
AB  - Dameshek first postulated a common myeloproliferative heritage for the
      myeloproliferative disorders, now termed neoplasms. This prescient observation
      was validated by the description of a common mutation in exon 14 of JAK2 for
      patients with essential thrombocythemia, polycythemia vera and primary
      myelofibrosis. In recent years, our knowledge of the molecular abnormalities
      underpinning these disorders has expanded significantly. At the same time, we
      have continued to use a classification based largely upon the first clinical
      descriptions of these entities, which sometimes proves problematic in
      differentiating between these conditions and normal reactive processes,
      myelodysplasia and between the myeloproliferative neoplasm entities themselves.
      Here, we discuss the pros and cons of a molecular classification and its
      potential utility in diagnosis, prognosis, and therapeutics.

PMID- 24091832
TI  - When to transplant MDS, and what to do when transplant fails.
AB  - Allogeneic hematopoietic stem cell transplantation (HCT) is still the only
      treatment modality with curative potential for patients with myelodysplastic
      syndromes. While early transplant-related mortality has improved during the last
      years, relapse risk following HCT still remains high, especially in older
      patients undergoing reduced-intensity conditioning. Therefore, when considering
      allogeneic HCT, in the absence of randomized data, emphasis should be put on
      patient selection and optimization of the pre-transplant and post-transplant
      period. In addition to a thorough comorbidity evaluation, risk stratification
      considering age, cytogenetics, grade of cytopenia, disease-related quality of
      life, as well as discussion of available treatment alternatives, are mandatory to
      decide when and how to perform allogeneic HCT. Since therapeutic options are
      often limited in patients relapsing after HCT, preventing relapse through
      maintenance strategies or minimal residual disease-directed therapy remains a
      central goal of current clinical research.

PMID- 24091833
TI  - Harnessing PD-L1-specific cytotoxic T cells for anti-leukemia immunotherapy to
      defeat mechanisms of immune escape mediated by the PD-1 pathway.

PMID- 24091834
TI  - Intimate partner violence screening among migrant/seasonal farmworker women and
      healthcare: a policy brief.
AB  - Migrant and seasonal farm working (MSFW) women report higher rates of intimate
      partner violence (IPV) as compared to the national average (Hazen and Soriano in
      Violence Against Women 13:562-582, 2007). Although prior researchers have
      indicated that implementing IPV screenings in healthcare settings significantly
      increases rates of identifying IPV (Nelson et al. in Ann Intern Med 156:1-17,
      2012; Ramsay et al. in Br Med J 325:314-318, 2002); many providers opt not to
      screen (Jonassen and Mazor in Acad Med 78(10):S20-S23, 2003; Smith et al. in Fam
      Community Health 20:1-18, 1998). The purpose of this policy brief is to review
      previous research related to IPV among MSFW women and, based on the findings,
      recommend policies that may help to improve the detection, intervention,
      resources, and available science with respect to this underserved population.

PMID- 24091835
TI  - Measurement of neopterin, TGF-beta1 and ACE in the exhaled breath condensate of
      patients with sarcoidosis.
AB  - Exhaled breath condensate (EBC) is a non-invasive method of sampling airway
      lining fluids in respiratory diseases. This may be useful in identifying exhaled
      biomarkers of granulomatous inflammation and pulmonary fibrosis in patients with
      sarcoidosis. The aim of this pilot study was to identify markers of granulomatous
      airway inflammation and disease activity including neopterin, transforming growth
      factor-beta1 (TGF-beta1) and angiotensin converting enzyme (ACE) in EBC. EBC was
      collected from 16 patients with sarcoidosis and 22 healthy control subjects. EBC
      neopterin, and active-TGF-beta1 were measured by ELISA. EBC-ACE activity was
      measured using a colorimetric assay. EBC neopterin was detectable in 3/20
      controls and 7/16 patients with sarcoidosis. Patients with sarcoidosis had
      greater mean neopterin levels compared to control subjects (0.57 +/- 0.45 nmol l(
      1) versus 0.41 +/- 0.22 nmol l(-1), p = 0.04). TGF-beta1 was detectable in the
      EBC of all subjects and concentrations were higher in patients with sarcoidosis
      compared with controls (115.5 +/- 79.6 pg mol(-1) versus 82.3 +/- 16.2 pg mol(
      1), p = 0.048). There was no difference in EBC ACE activity, which was only
      detectable in 3/20 healthy controls and 2/16 patients (p = 0.91). EBC markers of
      granulomatous inflammation are detectable at greater levels in patients with
      sarcoidosis compared to healthy controls subjects. Larger studies and development
      of sensitive assays are warranted to examine the disease correlates and
      predictive utility of these markers. 

PMID- 24091836
TI  - What we have learned about soft-tissue augmentation over the past 10 years.

PMID- 24091837
TI  - Outbreak-related mumps vaccine effectiveness among a cohort of children and of
      young adults in Germany 2011.
AB  - Mumps outbreaks in populations with high 2-dose vaccination coverage and among
      young adults are increasingly reported. However, data on the duration of vaccine
      induced protection conferred by mumps vaccines are scarce. As part of a supra
      regional outbreak in Germany 2010/11, we conducted two retrospective cohort
      studies in a primary school and among adult ice hockey teams to determine mumps
      vaccine effectiveness (VE). Via questionnaires we collected information on
      demography, clinical manifestations, and reviewed vaccination cards. We estimated
      VE as 1-RR, RR being the rate ratio of disease among two-times or one-time mumps
      vaccinated compared with unvaccinated persons. The response rate was 92.6%
      (100/108--children cohort) and 91.7% (44/48--adult cohort). Fourteen cases were
      identified in the children and 6 in the adult cohort. In the children cohort
      (mean age: 9 y), 2-dose VE was 91.9% (95% CI 81.0-96.5%). In the adult cohort
      (mean age: 26 y), no cases occurred among the 13 2-times vaccinated, while 1-dose
      VE was 50.0% (95% CI -9.4-87.1%). Average time since last vaccination showed no
      significant difference for cases and non-cases, but cases were younger at age of
      last mumps vaccination (children cohort: 2 vs. 3 y, P=0.04; adult cohort: 1 vs. 4
      y, P=0.03). We did not observe signs of waning immunity in the children cohort.
      Due to the small sample size VE in the adult cohort should be interpreted with
      caution. Given the estimated VE, very high 2-dose vaccination coverage is
      required to prevent future outbreaks. Intervention efforts to increase coverage
      must especially target young adults who received<2 vaccinations during childhood.

PMID- 24091838
TI  - Musculoskeletal symptoms and psychosocial work environment, among Swedish
      commercial pilots.
AB  - PURPOSE: The associations between psychosocial work conditions and health in
      pilots are understudied, and therefore, the associations between the psychosocial
      work conditions and musculoskeletal problems among Swedish commercial pilots were
      investigated. METHODS: In 2010, a self-administered questionnaire study was
      performed among pilots in one Swedish commercial airline: 354 pilots participated
      (61 %). Musculoskeletal symptoms and the psychosocial work conditions measured by
      the demand control social support model were investigated. Odds ratios (OR) with
      95 % confidence interval (95 % CI) were expressed per change of one unit on the
      interquartile score scale. RESULTS: Pilots on long-haul flights had less elbow
      symptoms (OR 0.34, 95 % CI 0.14-0.85), and women had more hand symptoms (OR 2.90,
      95 % CI 1.11-7.52). There were associations between high work demands and
      symptoms from the neck (OR 2.04, 95 % CI 1.45-2.88), shoulders (OR 1.46, 95 %
      1.05-2.03), elbows (OR 1.79, 95 % CI 1.10-2.90) and low back (OR 1.42, 95 % CI
      1.02-1.96) in pilots. Low social support was associated with symptoms from the
      neck (OR 1.87, 95 % 1.35-2.58), shoulders (OR 1.56, 95 % CI 1.14-2.14) and low
      back (OR 1.63, 95 % CI 1.18-2.24). Low supervisor support was associated with
      neck (OR 1.67, 95 % CI 1.22-2.27), shoulders (OR 1.38, 95 % CI 1.02-1.87) and low
      back symptoms (OR 1.48, 95 % CI 1.09-2.01). The associations were mainly found
      among first officers. CONCLUSIONS: Musculoskeletal symptoms in pilots can be
      affected by poor psychosocial work conditions such as high demands and low social
      support, especially for first officers. The psychosocial aspects of
      organisational changes in commercial airlines should be taken into consideration.

PMID- 24091840
TI  - [Health and well-being: eternal dilemma of public health].

PMID- 24091839
TI  - Negative clinical outcomes of medication resulting in emergency department
      visits.
AB  - PURPOSE: The results of analyses of patients' health problems related to
      medication use have been highly variable due to various factors, such as
      different study methodology, diverse variables determined, fields of study. The
      aim of our study was to determine the prevalence and preventability of negative
      clinical outcomes of medication (NCOMs). METHODS: This was a cross-sectional
      study performed in the emergency departments (EDs) of nine Spanish hospitals
      during a 3-month period. A two-stage probabilistic sampling method was used , and
      a systematic appraisal tool was used to identify the NCOMs based on information
      gathered through patient interview and review of the medical records. Case
      evaluations were conducted in two phases by pharmacists and physicians. The
      prevalence and preventability of NCOM were calculated. A homogeneity test was
      performed to assess potential differences in the prevalence for each hospital.
      RESULTS: A total of 4,611 patients were included in the study. The overall
      prevalence of NCOMs was 35.7 % [95 % confidence interval (CI) 33.3-38.1]. These
      NCOMs could be divided into three categories: ineffectiveness (18.2 %; 95 % CI
      16.2-20.1), necessity (14.9 %; 95 % CI 13.4-16.6), and lack of safety (2.4 %; 95
      % CI 1.9-2.8). About 81 % (95 % CI 80.1-82.3) of the NCOMs could have been
      prevented. CONCLUSIONS: NCOMs provoked approximately one-third of visits to the
      EDs, and a high percentage of these were preventable. Implementation of
      strategies for patient safety and pharmaceutical care could help to prevent these
      problems and optimize the use of medications.

PMID- 24091841
TI  - [Effectiveness of a training course on influenza vaccination in changing medical
      students' and healthcare workers' attitudes towards vaccination].
AB  - A questionnaire study was performed to evaluate the effectiveness of a continuing
      medical education course on influenza vaccination, held in October 2011, in
      changing physicians', medical students' and other health care workers' attitudes
      towards receiving vaccination for seasonal influenza. The questionnaire contained
      questions regarding influenza, influenza vaccination, and attitudes towards
      vaccination. Results show that course participants were more likely to get
      vaccinated against seasonal influenza in 2011 (i.e. following the course) with
      respect to 2010 and that all professional categories, except students, were
      positively influenced by the course. 

PMID- 24091842
TI  - [Management of cases of active pulmonary tuberculosis in diagnostic radiology
      departments in Italy: proposal of a checklist and role of radiology technicians].
AB  - Tuberculosis (TB) affects more than two billion people worldwide. In hospitals,
      the presence of suspect cases of infectious TB should be reported as quickly as
      possible. An anonymous questionnaire was administered to a sample of radiology
      technicians employed by several local health departments in Italy. The
      questionnaire contained questions regarding workplace characteristics, knowledge
      about precautions for preventing disease transmission, degree of collaboration
      between health professionals and departments regarding communicable diseases.
      Study results point to the presence of structural and organizational weaknesses
      as well as inadequate communication between healthcare workers and units. Eighty
      percent of surveyed technicians stated that patients with suspected TB may arrive
      in diagnostic radiology wards devoid of surgical mask. The authors suggest the
      adoption of a checklist to aid healthcare professionals and specifically X-Ray
      technicians in adopting a behavioral model for the management of patients with
      infectious TB. 

PMID- 24091843
TI  - [Wood dusts and neoplasms of the nose and paranasal sinuses: field investigations
      and laboratory experiments].
AB  - Nose and paranasal sinus cancers are among the diseases related to exposure to
      wood dusts. The aim of this study was to evaluate exposure to hardwood dust by
      workers in small carpentry industries in central Italy (Tuscany, Italy) employing
      from one to ten workers each, and to investigate pathogenetic mechanisms. The
      efficacy of ventilation systems was assessed and exposure levels determined.
      Exposure conditions of hardwood workers were then reproduced in the laboratory
      and a physical/kinetic model prepared to simulate patterns of air uptake by
      workers. Various parameters were then measured to investigate possible risk
      factors that may be related to the onset of the disease. In addition to particle
      size of wood dust, a factor that requires further investigation is the
      temperatures reached by wood dust during processing, which may lead to the
      formation of new harmful molecules. 

PMID- 24091844
TI  - Building successful collaborations between Public Health and Primary Health Care.
AB  - Public Health (PH) and Primary Health Care (PHC) need to be better integrated, at
      different levels of the healthcare system, in order to improve health and social
      outcomes. The aim of this study was to review international models and approaches
      supporting the integration of PH and PHC and to classify these according to their
      main focus. A literature search was performed using the main scientific
      databases, to identify national and international journal publications regarding
      models to support integration between PH and PHC. The final set of the documents
      provided a broad coverage of the topic. Four models of integration were
      identified: general integration, chronic disease prevention, targeted prevention
      or care delivery and infection control. Models differed in their levels of
      implementation, stages of development and focus. This review, by classifying the
      main characteristics and results of the experiences retrieved, indicates a
      relatively scarce use of integration models in the global health care landscape,
      with the exception of Canada. In fact, Canada has been a leader in developing
      models of integrated health systems that combine tailored approaches to influence
      personal health behaviour and community-oriented approaches to influence the
      health of the population. The review also revealed a general lack of experience
      in evaluating the sustainability of integration between PH and PHC, not only in
      terms of cost-effectiveness, but also in terms of better health and work
      conditions and self-perceived quality of care in the population. Collaboration
      between PH and PHC seems to be an important strategy for achieving principles of
      equity and access in health care and for ensuring a more equal distribution of
      health care services. 

PMID- 24091845
TI  - Livestock farming and atmospheric emissions.
AB  - Livestock farming produces atmospheric emissions that may pose a risk to workers
      and a disturbance to the population. Emissions into the atmosphere produced by
      livestock farming consist of gases such as ammonia, dust, compounds such as
      aliphatic hydrocarbons and bio-aerosols formed by microorganisms. Some gases,
      such as ammonia and hydrogen sulphide, have foul odours and are thus potentially
      annoying to the population. Gaseous or volatile molecules produced by livestock
      installations and related activities may have several adverse effects on health
      and environment. The most significant exposure certainly relates to workers in
      the confined spaces of farms, rather than to residents in the surrounding areas.
      In this article we examine potential hazards to farm workers and to the
      population living in the vicinity of livestock farms, arising from emissions into
      the atmosphere. 

PMID- 24091846
TI  - [Survey of the perceived quality of healthcare in some countries of the former
      Soviet block].
AB  - The health systems of countries of the Former Soviet Union are all based on
      Semashko's system, which is no longer active since 1991 when the fall of
      communism occurred. Post-soviet states have tried to create new healthcare
      systems that maintain universal access to care. The goal of this descriptive
      study, conducted from August 2009 to June 2012, was to investigate the perceived
      quality of healthcare services in selected post-Soviet states. A questionnaire
      was administered by trained staff, to samples of adult healthcare service users
      in five countries (Belarus, Moldova, the Baltic States, Romania, and Ukraine), to
      investigate different aspects of the health care systems in these countries.
      Results were analysed by gender, profession, age and country of origin. Overall,
      470 subjects participated in the study. Perceived quality of healthcare varied
      among different countries but an overall negative and pessimistic view of the
      future was identified. Gender, age group and profession were found to be
      determinants of perceived quality (p <0.05). The observed variations do not seem
      to be directly explained by the model of healthcare system adopted, rather by
      respondents' different socioeconomic and demographical standings. 

PMID- 24091847
TI  - [Old problems and new strategies in the fight against pertussis].
AB  - Pertussis is still a major Public Health problem. In fact, despite high
      vaccination coverage, several outbreaks have occurred in the last years all over
      the world, with thousands of cases and several deaths. Waning immunity seems to
      be the origin of this phenomenon, causing the shift of the peak incidence of the
      disease from school-age children, typical of the pre-vaccination era, to
      adolescents and adults. From these subjects the infection spreads to infants who
      have not yet been vaccinated or who have not completed the vaccination cycle. To
      reduce the incidence and the complications of pertussis in infants and immune
      compromised persons, booster doses are recommended and a "cocoon" vaccination
      strategy has been proposed. 

PMID- 24091848
TI  - In vitro generation of mature, naive antigen-specific CD8(+) T cells with a
      single T-cell receptor by agonist selection.
AB  - Peripheral blood T cells transduced with a tumor-specific T-cell receptor (TCR)
      face problems of auto-reactivity and lack of efficacy caused by cross-pairing of
      exogenous and endogenous TCR chains, as well as short term in vivo survival due
      to activation and growth factor-induced differentiation. We here studied an
      alternative strategy for the efficient generation of naive CD8(+) T cells with a
      single TCR. TCR-transduced human postnatal thymus-derived and adult mobilized
      blood-derived hematopoietic progenitor cells (HPCs) were differentiated to
      CD4(+)CD8(+) double-positive T cells using OP9-Delta-like 1 (OP9-DL1) cultures.
      Addition of the agonist peptide induced double positive cells to cross-present
      the peptide, leading, in the absence of co-stimulation, to cell cycle arrest and
      differentiation into mature CD8(+) T cells. Comprehensive phenotypic, molecular
      and functional analysis revealed the generation of naive and resting CD8(+) T
      cells through a process similar to thymic positive selection. These mature T
      cells show a near complete inhibition of endogenous TCRA and TCRB rearrangements
      and express high levels of the introduced multimer-reactive TCR. Upon activation,
      specific cytokine production and efficient killing of tumor cells were induced.
      Using this strategy, large numbers of high-avidity tumor-specific naive T cells
      can be generated from readily available HPCs without TCR chain cross-pairing. 

PMID- 24091849
TI  - A phase III concurrent chemoradiotherapy trial with cisplatin and paclitaxel or
      docetaxel or gemcitabine in unresectable non-small cell lung cancer: KASLC 0401.
AB  - PURPOSE: Concurrent chemoradiotherapy (CCRT) is recommended for the management of
      patients with unresectable non-small cell lung cancer (NSCLC). This prospective
      study aimed to compare the efficacy of concurrently delivered cisplatin doublets
      with paclitaxel, or docetaxel, or gemcitabine. METHODS: The main eligibility
      criteria consisted of previously untreated stage IIIB NSCLC. The subjects were
      randomized into three arms: paclitaxel 45 mg/m(2)/week (TP), docetaxel 20
      mg/m(2)/week (DP), and gemcitabine 350 mg/m(2)/week (GP) in addition to cisplatin
      20 mg/m(2)/week. Three-dimensional conformal radiotherapy was given once daily,
      weekly 5 fractions and the total prescription dose was 60-66 Gy. The primary
      endpoint was response rate, and the secondary endpoints were survival and
      toxicity. RESULTS: A total of 101 patients were recruited into this trial of whom
      93 (TP: 33, DP: 29, GP: 31) patients were treated with CCRT from March 2005 to
      July 2007. Similar response rates were observed across arms: TP: 63.6 %, DP: 72.4
      %, GP: 61.3 % (p = 0.679). There was no statistically significant difference of
      median survival (TP: 27.3, DP: 27.6, GP: 16.5 months, p = 0.771). In subgroup
      analysis, a survival benefit of consolidation chemotherapy was not seen, but
      leucopenia (63.2 %) and neutropenia (68.4 %) more than grade 3 were significantly
      high in DP arm. The grade >=3 radiation esophagitis was more frequent in the GP
      arm (22.6 %, p = 0.163). CONCLUSIONS: Among the three arms, no statistically
      significant difference in response rate, survival, and toxicity was observed.
      However, clinically significant radiation toxicity was more frequent in the GP
      arm.

PMID- 24091850
TI  - Angiotensin-(1-7) synergizes with colony-stimulating factors in hematopoietic
      recovery.
AB  - PURPOSE: Angiotensin (1-7) [A(1-7)] is a bioactive peptide of the renin
      angiotensin system that stimulates the number of bone marrow progenitors and
      hematopoietic recovery after myelosuppression. We evaluated the combination of
      A(1-7) with colony-stimulating factors, Neupogen and Epogen, on bone marrow
      progenitors and the recovery of circulating formed elements following
      chemotherapy. METHODS: Mice were injected with gemcitabine followed 2 days later
      with A(1-7). Circulating blood cells and bone marrow progenitors were measured
      over time. RESULTS: Combination of A(1-7) with Neupogen (the latter given only 3
      days starting at the white blood cell nadir) decreased the amount of Neupogen
      needed for optimal recovery by 10-fold. The progenitors measured include CFU
      GEMM, CFU-GM, CFU-Meg and BFU-E. A(1-7) increased recovery of all progenitors
      when given alone or in combination with Neupogen above that with Neupogen alone.
      Combination of A(1-7) with Epogen slightly increased (not significantly) red
      blood cell concentrations above those achieved by Epogen alone. However, in this
      model, A(1-7) or A(1-7) in combination with Epogen increased all erythroid
      progenitors with the largest effect on early erythroid progenitors (immature BFU
      E). CONCLUSIONS: Neupogen and Epogen acted synergistically with A(1-7) to
      increase the concentration of myeloid, megakaryocytic and erythroid progenitor
      cells in the bone marrow following chemotherapy suggesting that A(1-7)'s
      multilineage effect on early progenitors in the marrow facilitates proliferation
      in response to lineage-specific growth factors.

PMID- 24091852
TI  - Three-dimensional prediction of free-flap volume in autologous breast
      reconstruction by CT angiography imaging.
AB  - PURPOSE: The diagnostic use of computer tomography angiography (CTA) to identify
      perforating blood vessels for abdominal free-flap breast reconstruction was
      extended to estimate the three-dimensional (3D) preoperative flap volume and to
      compare it with the real intraoperative flap weights in order to (1) evaluate the
      accuracy of CTA-based 3D flap volume prediction, and (2) to analyze abdominal
      tissue estimation for required breast volume reconstruction. METHODS:
      Preoperative CTA was performed in 54 patients undergoing unilateral breast
      reconstruction with a free, deep, inferior epigastric artery perforator flap. 3D
      flap volumes ([Formula: see text]) based on CTA data were calculated and compared
      with the actual intraoperative flap weight (g). In addition, a breast volume to
      flap volume ratio was calculated to analyze whether the estimated 3D abdominal
      flap volume would match that of the breast to be removed. RESULTS: 40 CTA data
      sets (74.1 %) fulfilled the technical requirements for a reliable determination
      of flap volume. 3D CTA flap volume prediction showed no relevant differences to
      the actual flap weight (p = 0.44) and high correlations (r = 0.998, [Formula: see
      text]), allowing a prediction accuracy within 0.29 [Formula: see text] 3.0 %
      (range: from [Formula: see text]8.77 to 5.67 %) of the real flap weight.
      Significantly larger flap volumes were harvested compared with the actually
      required breast volumes ([Formula: see text]), leading to an average of 21 % of
      the remnant flap tissue potentially being discarded. CONCLUSIONS: CTA-based 3D
      flap volume prediction provides accurate preoperative guidelines concerning the
      needed amount of abdominal tissue that can be harvested to achieve acceptable
      symmetry.

PMID- 24091854
TI  - Automated liver lesion detection in CT images based on multi-level geometric
      features.
AB  - PURPOSE: Due to the increasing number of liver cancer cases in clinical practice,
      there is a significant need for efficient tools for computer-assisted liver
      lesion analysis. A wide range of clinical applications, such as lesion
      characterization, quantification and follow-up, can be facilitated by automated
      liver lesion detection. Liver lesions vary significantly in size, shape, density
      and heterogeneity, which make them difficult to detect automatically. The goal of
      this work was to develop a method that can detect all types of liver lesions with
      high sensitivity and low false positive rate within a short run time. METHODS:
      The proposed method identifies abnormal regions in liver CT images based on their
      intensity using a multi-level segmentation approach. The abnormal regions are
      analyzed from the inside-out using basic geometric features (such as asymmetry,
      compactness or volume). Using this multi-level shape characterization, the
      abnormal regions are classified into lesions and other region types (including
      vessel, liver boundary). The proposed analysis also allows defining the contour
      of each finding. The method was trained on a set of 55 cases involving 120
      lesions and evaluated on a set of 30 images involving 59 (various types of)
      lesions, which were manually contoured by a physician. RESULTS: The proposed
      algorithm demonstrated a high detection rate (92 %) at a low (1.7) false positive
      per case (precision 51 %), when the method was started from a manually contoured
      liver. The same level of false positive per case (1.6) and precision (51 %) was
      achieved at a somewhat lower detection rate (85 %), when the volume of interest
      was defined by a fully automated liver segmentation. CONCLUSIONS: The proposed
      method can efficiently detect liver lesions irrespective of their size, shape,
      density and heterogeneity within half a minute. According to the evaluation, its
      accuracy is competitive with the actual state-of-the-art approaches, and the
      contour of the detected findings is acceptable in most of the cases. Future work
      shall focus on more precise lesion contouring so that the proposed method can be
      a solid basis for fully automated liver tumour burden estimation.

PMID- 24091853
TI  - Design and initial evaluation of a treatment planning software system for MRI
      guided laser ablation in the brain.
AB  - PURPOSE: An open-source software system for planning magnetic resonance (MR)
      guided laser-induced thermal therapy (MRgLITT) in brain is presented. The system
      was designed to provide a streamlined and operator-friendly graphical user
      interface (GUI) for simulating and visualizing potential outcomes of various
      treatment scenarios to aid in decisions on treatment approach or feasibility.
      METHODS: A portable software module was developed on the 3D Slicer platform, an
      open-source medical imaging and visualization framework. The module introduces an
      interactive GUI for investigating different laser positions and power settings as
      well as the influence of patient-specific tissue properties for quickly creating
      and evaluating custom treatment options. It also provides a common treatment
      planning interface for use by both open-source and commercial finite element
      solvers. In this study, an open-source finite element solver for Pennes' bioheat
      equation is interfaced to the module to provide rapid 3D estimates of the steady
      state temperature distribution and potential tissue damage in the presence of
      patient-specific tissue boundary conditions identified on segmented MR images.
      RESULTS: The total time to initialize and simulate an MRgLITT procedure using the
      GUI was [Formula: see text]5 min. Each independent simulation took [Formula: see
      text]30 s, including the time to visualize the results fused with the planning
      MRI. For demonstration purposes, a simulated steady-state isotherm contour
      [Formula: see text] was correlated with MR temperature imaging (N = 5). The mean
      Hausdorff distance between simulated and actual contours was 2.0 mm [Formula: see
      text], whereas the mean Dice similarity coefficient was 0.93 [Formula: see text].
      CONCLUSIONS: We have designed, implemented, and conducted initial feasibility
      evaluations of a software tool for intuitive and rapid planning of MRgLITT in
      brain. The retrospective in vivo dataset presented herein illustrates the
      feasibility and potential of incorporating fast, image-based bioheat predictions
      into an interactive virtual planning environment for such procedures.

PMID- 24091855
TI  - Can antihypertensive medication interfere with the vicious cycle between
      hypertension and vascular calcification?
AB  - Vascular calcification is a phenomenon of disturbed calcium deposition, as part
      of the calcium that is supposed to be deposited to our bones, is lodged to our
      vessels. There are two forms of vascular calcification, each with a distinct
      anatomical distribution and clinical relevance, namely the intimal and medial
      calcification. Studies have demonstrated that hypertension may cause vascular
      calcification but also that both types of calcification, especially medial,
      promote arterial rigidity and hence hypertension. Implications of this two-way
      road are largely unknown as there is no consensus yet on their exact clinical
      value. However, several antihypertensive medications seem to be able to interfere
      with the cycle of high blood pressure and vascular calcium deposits. The present
      review summarizes the up-to-date data regarding the effect of antihypertensive
      medication on vascular calcification. 

PMID- 24091856
TI  - Covalent binding of a nickel macrocyclic complex to a silica support: towards an
      electron exchange column.
AB  - Ni(II)L(2), L(2) = 1-propyl-1,3,5,8,12-pentaazacyclotetradecane, was covalently
      bound to a silica support. This complex can be reversibly oxidized to the
      corresponding Ni(III) complex. The latter complex is relatively long lived.
      Therefore electron exchange columns based on this material can be prepared.

PMID- 24091857
TI  - Effects of selective serotonin reuptake inhibitors versus tricyclic
      antidepressants on cerebrovascular events: a nationwide population-based cohort
      study.
AB  - Depression is a common disorder worldwide and is strongly associated with stroke.
      Use of antidepressants could potentially decrease the risk of stroke in patients
      with depression. However, the role of selective serotonin reuptake inhibitors
      (SSRIs), the most frequently prescribed antidepressant in this era, in the risk
      of stroke showed inconsistent results. We aimed to assess the association between
      the use of different types of antidepressants, SSRIs and tricyclic
      antidepressants (TCAs), and the risk of cerebrovascular events in patients with
      depression or anxiety. A nationwide population-based cohort study was
      retrospectively conducted in patients with depression or anxiety who started to
      take SSRIs and TCAs identified from the Taiwan National Health Insurance claims
      database (2001-2009). We examined the association between the 2 types of
      antidepressants and incidence of stroke using a proportional hazard model
      adjusted for stroke risk factors. Among the 24,662 SSRI and 14,736 TCA
      initiators, the crude incidence rate for stroke was 10.03 and 13.77 per 100
      person-years, respectively. Selective serotonin reuptake inhibitor use was not
      associated with risk of stroke as compared with TCAs in the time-fixed analysis.
      After adjusting for baseline propensity scores in the time-varying analysis, SSRI
      use significantly reduced risk of stroke as compared with TCAs with the adjusted
      hazard ratio of 0.67 (95% confidence interval, 0.47-0.96). The effect persisted
      even after considering the antidepressant dosage (hazard ratio, 0.65 [0.42 to
      0.99]). In summary, use of SSRIs was associated with a reduced risk for stroke,
      as compared with TCAs, in this specific disease population. 

PMID- 24091858
TI  - Conditional probability of response or nonresponse of placebo compared with
      antidepressants or St John's Wort in major depressive disorder.

PMID- 24091859
TI  - Risk of perioperative blood transfusions and postoperative complications
      associated with serotonergic antidepressants in older adults undergoing hip
      fracture surgery.
AB  - Serotonergic antidepressants (SAds) are associated with bleeding-related adverse
      events. An increased risk of bleeding with SAds may have important implications
      in surgical settings. Our study evaluates the risk of red blood cell (RBC)
      transfusions and postoperative complications associated with SAds among older
      adults undergoing hip fracture surgery. We conducted a retrospective cohort study
      of individuals 66 years or older who underwent hip fracture surgery in Ontario,
      Canada. The risk of RBC transfusion among current users of SAds and
      nonserotonergic antidepressants (NSAds) was compared with recent former SAd
      users. Secondary outcomes included measures of postoperative morbidity and
      mortality. Subgroup analyses were undertaken in groups who were coprescribed
      other medications known to effect bleeding. Multivariable logistic regression was
      utilized to determine the odds ratios (ORs) for antidepressants and postoperative
      outcomes. A total 11,384 individuals were included in the study sample. Current
      SAd users had an increased risk of RBC transfusion compared with recent former
      users of SAds (OR, 1.28; 95% confidence interval, 1.14-1.43) as did current NSAd
      users (OR, 1.17; 95% confidence interval, 1.03-1.33). The risk of RBC transfusion
      with SAds or NSAds was further increased among individuals receiving antiplatelet
      agents. However, postoperative morbidity and mortality were not increased among
      either group of antidepressant users. In conclusion, SAds are associated with an
      increased risk of RBC transfusions, although this does not appear to result in
      major postoperative complications. Clinicians should be aware of this increased
      risk, although routine discontinuation of antidepressants before surgery is
      likely unwarranted in most cases. 

PMID- 24091860
TI  - Sublingual methadone as an alternative to oral methadone for the treatment of
      breakthrough cancer pain.

PMID- 24091861
TI  - Single-stage repair of the anterior chest wall following sternal destruction
      complicated by mediastinitis.
AB  - PURPOSE: Although various techniques have been described, the ideal
      reconstructive procedure for treating massive sternal fragmentation and necrosis
      is still a matter of debate. Sometimes, reconstruction is so challenging that
      repetitive operations are required, particularly when complicated by
      mediastinitis and sternal osteomyelitis. METHODS: Five patients (three males, two
      females, median age 66) with severe osteomyelitis and sternal destruction after
      receiving myocardial revascularization underwent partial or radical sternal
      resection, omental flap transposition, titanium mesh implantation and rectus
      abdominis muscle flap transposition. The final procedure involved single-stage
      closure. RESULTS: One patient died 9 days after the final procedure due to
      pneumonia and septicemia. The other patients received antibiotics for at least 6
      weeks postoperatively. The mean hospital stay was 36 days. Optimal wound healing
      was observed, with acceptable cosmetic disorders. CONCLUSIONS: Although lateral
      sternal support is the first-line surgical treatment for sternal dehiscence,
      performing primary closure of complicated defects is often impossible. Aggressive
      treatment modalities are required in such cases for anterior chest wall defects.
      This technique provides the ability to perform rigid and stable sternal closure
      in complicated cases.

PMID- 24091862
TI  - Recent trends in hepatectomy for elderly patients with hepatocellular carcinoma.
AB  - PURPOSE: The incidence of hepatocellular carcinoma (HCC) in the elderly
      population has recently been increasing. In this study, we focused on a recent 10
      year survey, and compared the clinicopathological features and postoperative
      outcomes of HCC in elderly (>=75 years of age) and younger patients (<75 years of
      age). METHODS: A total of 255 patients who underwent hepatectomy for HCC from
      2001 to 2010 at Wakayama Medical University Hospital were reviewed. The clinical
      characteristics were compared between the elderly and younger patients. The risk
      factors for postoperative complications and prognostic factors were identified
      using the multivariate analyses. RESULTS: A total of 66 patients were classified
      as elderly patients. The incidence of HCC without viral liver disorders was
      significantly high in the elderly group than in the younger group. The
      independent risk factors [odds (95% confidence intervals)] for postoperative
      complications were an ASA score of 3 [2.57 (1.20-5.49)] and the length of the
      operation [1.41 (1.09-1.81)]. The survival was similar between the two groups,
      and the only independent prognostic factor for survival in the elderly patients
      was vessel invasion. CONCLUSIONS: HCC derived from non-viral liver disorders was
      dominant in the elderly patients. Aging itself was not a risk factor for
      postoperative complications or the survival outcome.

PMID- 24091863
TI  - Infusion of 50% glucose solution to occlude an intrahepatic portosystemic venous
      shunt before percutaneous transhepatic portal embolization: report of a case.
AB  - A 68-year-old man with cholangiocarcinoma underwent percutaneous transhepatic
      portal embolization to expand the indication for hepatic resection. Selective
      right posterior portography revealed an intrahepatic portosystemic venous shunt
      (IPSVS) connecting the segment VII branch to the right hepatic venous branch. An
      infusion of 50 % glucose solution was given to occlude the shunt. This is novel
      management for IPSVSs when they are numerous, small, or torturous, and makes the
      subsequent procedures simpler, shorter, and less expensive. 

PMID- 24091865
TI  - Robust self-healing hydrogels assisted by cross-linked nanofiber networks.
AB  - Given increasing environmental and energy issues, mimicking nature to confer
      synthetic materials with self-healing property to expand their lifespan is highly
      desirable. Just like human skin recovers itself upon damage with the aid of
      nutrient-laden blood vascularization, designing smart materials with
      microvascular network to accelerate self-healing is workable but continues to be
      a challenge. Here we report a new strategy to prepare robust self-healing
      hydrogels assisted by a healing layer composed of electrospun cross-linked
      nanofiber networks containing redox agents. The hydrogels process high healing
      rate ranging from seconds to days and great mechanical strengths with storage
      modulus up to 0.1 MPa. More interestingly, when the healing layer is embedded
      into the crack of the hydrogel, accelerated self-healing is observed and the
      healing efficiency is about 80%. The healing layer encourages molecular diffusion
      as well as further cross-linking in the crack region of the hydrogel, responsible
      for enhanced healing efficiency.

PMID- 24091864
TI  - Deconvoluting the obesity and breast cancer link: secretome, soil and seed
      interactions.
AB  - Obesity is associated with increased risk of breast cancer in postmenopausal
      women and is linked with poor prognosis in pre- and postmenopausal breast cancer
      patients. The mechanisms underlying the obesity-breast cancer connection are
      becoming increasingly clear and provide multiple opportunities for primary to
      tertiary prevention. Several obesity-related host factors can influence breast
      tumor initiation, progression and/or response to therapy, and these have been
      implicated as key contributors to the complex effects of obesity on cancer
      incidence and outcomes. These host factors include components of the secretome,
      including insulin, insulin-like growth factor-1, leptin, adiponectin, steroid
      hormones, cytokines, vascular regulators, and inflammation-related molecules, as
      well as the cellular and structural components of the tumor microenvironment.
      These secreted and structural host factors are extrinsic to, and interact with,
      the intrinsic molecular characteristics of breast cancer cells (including breast
      cancer stem cells), and each will be considered in the context of energy balance
      and as potential targets for cancer prevention. 

PMID- 24091866
TI  - MDCT of acute cecal conditions.
AB  - The cecum comprises a relatively short segment of the gastrointestinal tract, but
      it can be affected by numerous acute conditions. Acute conditions may arise from
      processes primary to the cecum, such as volvulus, bascule, neoplasm, and trauma.
      Alternatively, acute conditions can be due to secondary to systemic or nearby
      pathology, such as infection, inflammatory processes, ischemia, and infarction.
      While it is common to suspect appendicitis as the etiology of acute right lower
      quadrant abdominal pain, the cecum should also be considered as a potential cause
      of pain, especially in the setting of an abnormal or absent appendix. Multi
      detector computed tomography (MDCT) has evolved to become the best imaging
      modality to evaluate patients presenting with right lower quadrant abdominal pain
      or suspected acute cecal pathology. Strengths of MDCT include rapid acquisition
      of images, high spatial resolution, and ability to create multi-planar
      reconstructed images. In this pictorial review, we illustrate and describe key
      MDCT findings for various acute cecal conditions with which the emergency
      radiologist should be familiar.

PMID- 24091867
TI  - Thermal transport in lattice-constrained 2D hybrid graphene heterostructures.
AB  - The thermal transport properties of hybrid graphene/h-BN heterostructures are
      investigated using atomistic simulations. While the thermal conductivity is
      observed to be significantly limited perpendicular to the graphene/h-BN
      interface, it is tunable via a composition parallel to the interface. In
      particular we show that the thermal transport parallel to the interface can be
      understood by viewing the hybrid system as a series of individual embedded
      graphene nanoribbons (GNRs) constrained by neighboring h-BN. A mechanistic model
      is proposed to relate the thermal conductivities of the embedded and free
      standing GNRs through a linear function of the composition. The model predictions
      are demonstrated to be in good agreement with the simulation results.

PMID- 24091868
TI  - Newly diagnosed immune thrombocytopenia: update on diagnosis and management.
AB  - Immune thrombocytopenia (ITP) continues to intrigue pediatricians and
      hematologists alike. Patients can have a dramatic presentation with wide-spread
      bleeds over a few days. There is an aura and fear of intra-cranial hemorrhage
      that drives the physician to recommend and the patient's family to accept drug
      treatment. Difference of opinion among physicians in the recommendations for
      treatment is not uncommon, even though recent evidence-based guidelines recommend
      a conservative, observation-based approach for the majority of patients with
      newly diagnosed childhood ITP. It is important to note that a specific 'platelet
      cut-off count', is no longer suggested as an indication by itself to recommend
      drug therapy. The manuscript is an update on newly diagnosed ITP in children.
      Recent changes in definitions and recommendations for treatment are highlighted.
      Pros and cons of 1st line drugs, including corticosteroids, intravenous
      immunoglobulin and anti-D are listed. Adjunctive therapies for the management of
      epistaxis and menorrhagia are described. Role of splenic artery embolization and
      emergency splenectomy in the backdrop of severe thrombocytopenia is discussed.
      Realistic case scenarios, common errors and frequently asked questions are
      included for a practical and easy reading. 

PMID- 24091869
TI  - ADad 6: the predictive factors for Anxiety Disorders among adolescents in a rural
      community population in India.
AB  - OBJECTIVE: Development of Anxiety Disorders (AD) among adolescents is the
      interplay of risk and protective factors that have a biological and environmental
      basis. This study documents the predictive factors associated with the presence
      of AD among adolescents in India. METHODS: The authors prospectively collected
      data for 500 adolescents in a community with independent, trained raters. Data on
      the dependent variable of AD and its subtypes was collected with Screen for Child
      Anxiety Related Emotional Disorders (SCARED), Socio-economic status with Modified
      Kuppuswamy Scale, depression with Beck Depression Inventory and the other
      independent variables with a specially designed proforma. The predictive factors
      for the presence of AD were analyzed with univariate and multivariate regression
      analyses appropriately, and a parsimonious predictive model was built. RESULTS:
      Gender (adjusted OR = 1.96), and presence of Depressive Disorder (adjusted OR =
      24.14) emerged as independent risk factors. Level of education came-out as a
      protective factor (adjusted OR = 0.66). Adolescent girls were at risk of
      developing Separation Anxiety Disorder (SeAD) (adjusted OR = 3.51) and Social
      Anxiety Disorder (SoAD) (adjusted OR = 1.69). Level of education had a protective
      influence on SeAD (adjusted OR = 0.39) and SoAD (adjusted OR = 0.59) among those
      doing high school. This protective effect increased if they were in higher
      secondary school for SeAD (adjusted OR = 0.21) and SoAD (adjusted OR = 0.22). In
      the multivariate model age of the adolescent also gained significance and the 3
      factor model had a good model fit. Panic Disorder and Generalized Anxiety
      Disorder were not related to any specific variable. CONCLUSIONS: Identifying the
      factors associated with AD and the subtypes can be used to predict, prevent or
      treat these disorders in this population. Educating adolescent girls to higher
      secondary school level seem to be an important step in this direction.

PMID- 24091870
TI  - The effects of aging on postural control and selective attention when stepping
      down while performing a concurrent auditory response task.
AB  - PURPOSE: To investigate the effects of aging on postural control and cognitive
      performance in single- and dual-tasking. METHODS: A cross-sectional comparative
      design was conducted in a university motion analysis laboratory. Young adults (n
      = 30; age 21.9 +/- 2.4 years) and older adults (n = 30; age 71.9 +/- 6.4 years)
      were recruited. Postural control after stepping down was measured with and
      without performing a concurrent auditory response task. Measurement included: (1)
      reaction time and (2) error rate in performing the cognitive task; (3) total sway
      path and (4) total sway area after stepping down. RESULTS: Our findings showed
      that the older adults had significantly longer reaction times and higher error
      rates than the younger subjects in both the single-tasking and dual-tasking
      conditions. The older adults had significantly longer reaction times and higher
      error rates when dual-tasking compared with single-tasking, but the younger
      adults did not. The older adults demonstrated significantly less total sway path,
      but larger total sway area in single-leg stance after stepping down than the
      young adults. The older adults showed no significant change in total sway path
      and area between the dual-tasking and when compared with single-tasking
      conditions, while the younger adults showed significant decreases in sway.
      CONCLUSION: Older adults prioritize postural control by sacrificing cognitive
      performance when faced with dual-tasking.

PMID- 24091871
TI  - Stent encrustation in feline and human artificial urine: does the low molecular
      weight composition account for the difference?
AB  - Anecdotal evidence suggests that the rate of encrustation on JJ stents placed in
      domesticated cats appears to be decreased as compared to humans. Our study tests
      the hypothesis that this may be due to specific differences in the chemical
      composition of human and feline urine. Artificial human and feline urine
      solutions were used in an in vitro encrustation model where an 80 % stent
      encrustation could be expected after 7 weeks of incubation. Scanning electron
      microscopy (SEM) was used to analyse crystal morphology. Energy dispersive X-ray
      spectrometry (EDS) was used to assess composition weight. The percentage of
      surface coverage of encrustation on the respective stents was quantified using
      image J Java plug-in software. No significant difference was observed between
      both solutions with regard to quality and quantity of stent encrustation.
      Crystals were formed in both solutions as a mixture of Ca-dihydrate and Ca
      monohydrate. The study shows that there is no significant difference in the rate
      of encrustations on JJ stents incubated in artificial feline or human urine. This
      suggests that a possible difference in stent encrustation between cats and humans
      is due to factors other than the inorganic biochemical composition of the urines
      alone. Keeping in mind a true species difference, analysis of urinary
      macromolecules and proteins will be the logical next step. 

PMID- 24091872
TI  - Regulation and function of mitophagy in development and cancer.
AB  - Beyond its role in recycling intracellular components nonselectively to sustain
      survival in response to metabolic stresses, autophagy can also selectively
      degrade specific cargoes such as damaged or dysfunctional organelles to maintain
      cellular homeostasis. Mitochondria, known as the power plant of cells, are the
      critical and dynamic organelles playing a fundamental role in cellular
      metabolism. Mitophagy, the selective autophagic elimination of mitochondria, has
      been identified both in yeast and in mammalian cells. Moreover, defects in
      mitophagy may contribute to a variety of human disorders such as
      neurodegeneration and myopathies. However, the role of mitophagy in development
      and cancer remains largely unclear. In this review, we summarize our current
      knowledge of the regulation and function of mitophagy in development and cancer. 

PMID- 24091873
TI  - In vivo excursion of the temporalis muscle-tendon unit using electrical
      stimulation: application in the design of smile restoration surgery following
      facial paralysis.
AB  - IMPORTANCE: The temporalis muscle has the potential to substitute for the
      function of paralyzed facial muscles in a single-stage procedure when transferred
      as a muscle-tendon unit (MTU). OBJECTIVE: To measure the available excursion of
      the temporalis MTU after release from the coronoid. DESIGN, SETTING, AND
      PARTICIPANTS Thirteen consecutive patients undergoing the temporalis MTU transfer
      procedure for facial reanimation participated in this study in an academic
      research setting. MAIN OUTCOMES AND MEASURES: Using transcutaneous electrical
      stimulation of the temporalis muscle, excursion of the temporalis muscle after
      its release as an MTU was recorded. Tension was varied on the released tendon
      during electrical stimulation of the muscle to determine the optimal muscle
      length at which the maximum excursion could be achieved. The tendon was inserted
      at the modiolus at the determined muscle length, and excursion of the oral
      commissure was recorded. Excursion data were then measured from the video
      recordings. RESULTS The mean excursion of the temporalis tendon after its
      detachment from the mandible and stimulation at an optimized passive tension was
      20.6 mm (range, 14-30 mm) (n = 9). Following tendon insertion, the mean oral
      commissure excursion was 15.5 mm (range, 8-23 mm) (n = 13). CONCLUSIONS AND
      RELEVANCE: The temporalis MTU has adequate available excursion following
      mobilization for dynamic reanimation of the paralyzed face. Electrical
      stimulation of the released temporalis tendon gives useful information that is
      reproducible and can be an important intraoperative adjunct to setting the MTU at
      an optimal tension to maximize force generation and excursion. LEVEL OF EVIDENCE:
      NA.

PMID- 24091876
TI  - Highly selective electrocatalytic dehydrogenation at low applied potential
      catalyzed by an Ir organometallic complex.
AB  - A homogeneous organometallic Ir complex was shown to catalyze the electro
      oxidation of 4-methoxybenzyl alcohol to p-anisaldehyde at a very low applied
      potential with remarkably high selectivity and Faradaic efficiency. In the
      chemical catalysis, when stoichiometric oxidant and anionic base were used to
      separately accept electrons and protons, aldehyde selectivity was in agreement
      with electrolysis results. 

PMID- 24091875
TI  - MYC amplification and overexpression in primary cutaneous angiosarcoma: a
      fluorescence in-situ hybridization and immunohistochemical study.
AB  - MYC, a proto-oncogene located on chromosome 8q24, is involved in the control of
      cell proliferation and differentiation. Previous studies have documented high
      level MYC gene amplification and MYC overexpression by immunohistochemistry (IHC)
      in post-irradiation angiosarcomas, but not in primary cutaneous angiosarcoma (AS
      C) or in other radiation-associated vascular proliferations, such as atypical
      vascular lesions. Prompted by our recent finding of MYC amplification in a
      primary hepatic AS, we analyzed a large number of well-characterized AS-C for MYC
      amplification and protein overexpression. Formalin-fixed, paraffin-embedded
      blocks from 38 AS-C were retrieved from our archives and were examined by IHC
      analysis and fluorescence in-situ hybridization (FISH), using a commercially
      available antibody and probe. For FISH analysis, the number of copies of MYC was
      compared with the control gene, CEN8 (MYC/CEN8 ratio). All cases occurred on sun
      exposed skin; no patient was known to have a history of therapeutic irradiation.
      Possible associations between survival and a wide variety of clinicopathological
      variables were evaluated using the log-rank test. By IHC analysis, MYC
      overexpression was present in 9/38 (24%) AS-C (2-3+: 6 cases, 16%; 1+: 3 cases,
      8%). By FISH analysis, 2/5 (40%) informative cases with 2-3+ immunostaining
      showed high-level gene amplification. One additional case with 3+ immunostaining
      showed higher level aneusomy of chromosome 8 (5-8 MYC and CEN8). Two out of
      fourteen (14%) IHC-negative cases also carried MYC amplification (one high level
      and one lower level). Low copy number gain of chromosome 8 (3-5 MYC and CEN8) was
      observed in AS-C with or without MYC expression. MYC amplification and MYC
      protein overexpression were not correlated with clinical outcome. We have shown,
      for the first time, MYC gene amplification and protein overexpression in primary
      (non-radiation-associated) AS of the skin. MYC protein overexpression in cases
      lacking gene amplification likely reflects other mechanisms of MYC activation.
      The study of a larger number of AS-C showing MYC amplification may be necessary
      to determine whether the behavior of such cases differs from their more common
      non-amplified counterparts. 

PMID- 24091874
TI  - Dietary approaches to prevent hypertension.
AB  - Elevated blood pressure arises from a combination of environmental and genetic
      factors and the interactions of these factors. A substantial body of evidence
      from animal studies, epidemiologic studies, meta-analyses, and randomized
      controlled trials has demonstrated that certain dietary patterns and individual
      dietary elements play a prominent role in the development of hypertension.
      Changes in diet can lower blood pressure, prevent the development of
      hypertension, and reduce the risk of hypertension-related complications. Dietary
      strategies for the prevention of hypertension include reducing sodium intake,
      limiting alcohol consumption, increasing potassium intake, and adopting an
      overall dietary pattern such as the DASH (Dietary Approaches to Stop
      Hypertension) diet or a Mediterranean diet. In order to reduce the burden of
      blood pressure-related complications, efforts that focus on environmental and
      individual behavioral changes that encourage and promote healthier food choices
      are warranted. 

PMID- 24091878
TI  - Functionalization of hydrogenated silicene with alkali and alkaline earth metals
      for efficient hydrogen storage.
AB  - First principles density functional theory has been employed to investigate the
      electronic structure along with the stability, bonding mechanism, band gap and
      charge transfer of metal functionalized hydrogenated silicene (SiH), or silicane,
      in order to envisage the hydrogen storage capacity. Various metal adatoms
      including Li, Na, K, Be, Mg and Ca have been doped on the most stable chair like
      configuration of silicane. The corresponding binding energies and charge transfer
      mechanism have been discussed from the perspective of H2 storage ability. The Li
      and Na metal adatoms have been found to be ideally suitable not only for their
      strong metal to substrate binding and uniform distribution over the substrate but
      also for their high capacity for storage of hydrogen. The stability of both Li
      and Na functionalized SiH has also been confirmed by MD simulations. It was found
      that both Li(+) and Na(+) adsorbed four H2 molecules attaining reasonably high
      storage capacities of 6.30 wt% and 5.40 wt% respectively with average adsorption
      energies lying within the range suitable for practical H2 storage applications,
      in contrast with alkaline earth metals. 

PMID- 24091879
TI  - Reduction of effective dose and organ dose to the eye lens in head MDCT using
      iterative image reconstruction and automatic tube current modulation.
AB  - AIMS: To compare the effective and eye lens radiation dose in helical MDCT brain
      examinations using automatic tube current modulation in conjunction with either
      standard filtered back projection (FBP) technique or iterative reconstruction in
      image space (IRIS). METHODS: Of 400 adult brain MDCT examinations, 200 were
      performed using FBP and 200 using IRIS with the following parameters: tube
      voltage 120 kV, rotation period 1 second, pitch factor 0.55, automatic tube
      current modulation in both transverse and longitudinal planes with reference mAs
      300 (FBP) and 200 (IRIS). Doses were calculated from CT dose index and dose
      length product values utilising ImPACT software; the organ dose to the lens was
      derived from the actual tube current-time product value applied to the lens.
      Image quality was assessed by two independent readers blinded to the type of
      image reconstruction technique. RESULTS: The average effective scan dose was
      1.47+/-0.26 mSv (FBP) and 0.98+/-0.15 mSv (IRIS), respectively (33.3% decrease).
      The average organ dose to the eye lens decreased from 40.0+/-3.3 mGy (FBP) to
      26.6+/-2.0 mGy (IRIS, 33.5% decrease). No significant change in diagnostic image
      quality was noted between IRIS and FBP scans (P=0.17). CONCLUSION: Iterative
      reconstruction of cerebral MDCT examinations enables reduction of both effective
      and organ eye lens dose by one third without signficant loss of image quality.

PMID- 24091880
TI  - Daphnoretin-induced apoptosis in HeLa cells: a possible mitochondria-dependent
      pathway.
AB  - Daphnoretin is a bicoumarin compound isolated from a natural product, Wikstroemia
      indica, which has been used to treat many diseases. It has strong antiviral and
      anti-tumor activities. Taking the anti-tumor activity of daphnoretin as a
      starting point, the present study aimed to test the pro-apoptotic effect of
      daphnoretin and its underlying mechanism in HeLa cells. The inhibitory effects of
      daphnoretin on viability and proliferation of HeLa cells were determined by the
      MTT assay. Daphnoretin-induced apoptotic morphological changes were analyzed by
      mitochondrial membrane potential and Hoechst staining. The number and stage of
      apoptotic HeLa cells were determined by flow cytometry. Gene expression was
      determined by reverse-transcription polymerase chain reaction. Protein expression
      was determined by western blot. The caspase activity of HeLa cells was detected
      by a caspase-3 and caspase-9 colorimetric assay kit. We found that daphnoretin
      significantly inhibited HeLa cells' viability by the MTT assay and flow
      cytometry. The nuclei of the apoptotic cells exhibited strong, blue fluorescence
      in Hoechst staining. Bax mRNA and protein levels were increased while bcl-2 mRNA
      levels were decreased after daphnoretin treatment. Daphnoretin also activated
      both caspase-3 and caspase-9. These findings suggest that daphnoretin promotes
      apoptosis of HeLa cells in a mitochondria-mediated way. Daphnoretin therefore has
      potential to be a promising drug to treat uterine cervix cancer. 

PMID- 24091881
TI  - Characterization of embryonic stem-like cells derived from HEK293T cells through
      miR302/367 expression and their potentiality to differentiate into germ-like
      cells.
AB  - Human induced pluripotent stem (iPS) cells have great value for regenerative
      medicine, but are facing problems of low efficiency. MicroRNAs are a recently
      discovered class of 19-25 nt small RNAs that negatively target mRNAs. miR302/367
      cluster has been demonstrated to reprogram mouse and human somatic cells to iPS
      cells without exogenous transcription factors, however, the repetition and
      differentiation potentiality of miR302/367-induced pluripotent stem (mirPS) cells
      need to be improved. Here, we showed overexpression of miR302/367 cluster
      reprogrammed human embryonic kidney 293T cells into mirPS cells in serum-free
      N2B27-based medium. The mirPS cells had similar morphology with embryonic stem
      cells, and expressed pluripotent markers including Oct4, Sox2, Klf4, and Nanog.
      In addition, through formation of embryoid bodies, various cells and tissues from
      three germ layers could be determined. Moreover, we examined the potential of
      mirPS cells differentiating into germ cells both in vitro and in vivo. Taken
      together, these data might provide a new source of cells and technique for the
      investigation of the mechanisms underlying reprogramming and pluripotency. 

PMID- 24091882
TI  - Long-term results of radiation oncology seminar for medical students and
      residents held between 1995 and 2011: career paths of the participants.
AB  - PURPOSE: The radiation oncology seminar for medical students and residents was
      initiated by the Japanese Society for Therapeutic Radiology and Oncology (JASTRO)
      with the aim of increasing the numbers of radiation oncologists. We investigated
      the long-term results related to the career paths of the program participants.
      METHODS: This study enrolled 531 individuals who were medical students and
      residents at the time of program participation, between 1995 and 2011. We
      surveyed participants with regard to their affiliation status with the Japan
      Radiological Society (JRS) and JASTRO and whether they were board-certified
      radiation oncologists. RESULTS: Forty-two percent of the participants were
      members of JRS and 26.4 % were members of JASTRO. The membership status with
      JASTRO was investigated in program participants from 2004 to 2009, and comparison
      by status revealed that 30.1 % of medical students and 47.2 % of residents were
      members, with a significant difference (p = 0.013). As high as 92.3 % of the
      participants in the 1995-2001 cohort who had joined JRS and JASTRO were board
      certified radiation oncologists. CONCLUSION: This program has greatly contributed
      to increasing the numbers of radiation oncologists. Because residents had a
      higher rate of affiliation than medical students, it is necessary to share
      information with not only medical universities, but also teaching hospitals.

PMID- 24091883
TI  - Multifunctionality of rare earth doped nano ZnSb2O6, CdSb2O6 and BaSb2O6:
      photocatalytic properties and white light emission.
AB  - Undoped MSb2O6 (where M = Zn, Cd, Ba) and single and double doped MSb2O6:RE
      (where RE = Tb(3+) and Eu(3+)) nanophosphors were synthesized through a simple
      sonochemical process and characterized by X-ray diffraction (XRD), scanning
      electron microscopy (SEM), transmission electron microscopy (TEM), energy
      dispersive X-ray spectroscopy (EDS), diffuse reflectance (DRS) and
      photoluminescence (PL) spectrophotometry. The TEM micrographs show that the
      resulting nanoparticles have mostly a spherical shape. Energy transfer was
      observed from the host to the dopant ions and characteristic green emissions from
      Tb(3+) ions and red emissions from Eu(3+) ions were observed. The chromaticity
      diagrams of the ZnSb2O6:Tb(3+)(1.2%):Eu(3+)(0.8%),
      CdSb2O6:Eu(3+)(0.5%):Tb(3+)(1.5%) and BaSb2O6:Eu(3+)(1%):Tb(3+)(1%) nanophosphors
      yielded CIE and CCT (correlated color temperature) values in the white light
      region. The photocatalytic activities of the undoped and double doped antimonates
      were evaluated for the degradation of rhodamine B (RhB) under UV light. Undoped
      MSb2O6 (where M = Zn, Cd, Ba) as well as ZnSb2O6:Tb(3+)(1.2%):Eu(3+)(0.8%),
      CdSb2O6:Eu(3+)(0.5%):Tb(3+)(1.5%) and BaSb2O6:Eu(3+)(1%):Tb(3+)(1%) samples
      exhibited good photodegradation capacity for RhB. Thus double doped
      ZnSb2O6:Tb(3+)(1.2%):Eu(3+)(0.8%), CdSb2O6:Eu(3+)(0.5%):Tb(3+)(1.5%) and
      BaSb2O6:Eu(3+)(1%):Tb(3+)(1%) can be termed a bifunctional material exhibiting
      both photocatalytic properties and white light emission. 

PMID- 24091885
TI  - Inflammation, myocardial dysfunction, and mortality in children with septic
      shock: an observational study.
AB  - We aimed to investigate whether nuclear factor kappa-B activation, as evaluated
      by gene expression of its inhibitor (I-kappaBalpha) and cytokine serum levels,
      was associated with myocardial dysfunction and mortality in children with septic
      shock. Twenty children with septic shock were prospectively enrolled and grouped
      according to ejection fraction (EF) <45% (group 1) or EF >=45% (group 2) on the
      first day after admission to the pediatric intensive care unit. No interventions
      were made. In the first day, patients from group 1 (n = 6) exhibited
      significantly greater tumor necrosis factor-alpha (TNF-alpha) and interleukin
      (IL)-10 plasma levels. However, I-kappaBalpha gene expression was not different
      in both groups. Mortality and number of complications were significantly greater
      in group 1. Patients who died had greater plasma concentrations of TNF-alpha. In
      conclusion, TNF-alpha and IL-10 are involved in myocardial dysfunction
      accompanying septic shock in children, and TNF-alpha is associated with
      mortality.

PMID- 24091886
TI  - Preconception healthcare and congenital disorders: systematic review of the
      effectiveness of preconception care programs in the prevention of congenital
      disorders.
AB  - Congenital disorders are a leading cause of global burden of disease; the birth
      prevalence remains constant at 6%. Initiating preconception care before pregnancy
      may be an effective strategy to reduce congenital disorders and improve the
      health of reproductive-age women. Our objectives are: (1) To identify components
      of preconception interventions, (2) to assess the effectiveness of preconception
      interventions in reducing the burden of congenital disorders, and (3) to
      prioritize these interventions. Medline and Science Direct search terms included:
      preconception, pre-pregnancy, childbearing, reproduction, care, intervention,
      primary care, healthcare, model, program, prevention, trial, efficacy,
      effectiveness, congenital disorders OR abnormalities. Inclusion criteria were:
      (1) English, (2) human subjects, (3) women of childbearing age, (4) 1980-current
      data, (5) all countries, (6) experimental studies, (7) systematic reviews or meta
      analysis, (8) program reports/evaluations. Data was collected and abstracted by
      two independent reviewers. To prioritize preconception interventions likely to
      have the largest impact at a population level, a ranked scoring system was
      created incorporating the following: (1) quality of evidence supporting the
      intervention, (2) effect size of the intervention, and (3) global burden of the
      specific congenital disease. Preconception interventions include risk screening,
      education, motivational counseling, disease optimization and specialist referral.
      The most effective interventions, based on the strength of evidence, size of
      impact of intervention, and disease burden are: folic acid
      fortification/supplementation, diabetic control, smoking and alcohol
      interventions, HIV management, thrombophillia screening, obesity prevention and
      epilepsy management. Although multiple conditions require preconception
      attention, only nine interventions have evidence to support their effect on
      congenital disorders through a randomised control trial, systematic review or
      meta-analysis. There is a need for more high-level research in evaluating certain
      preconception interventions. These findings have significant implications on
      planning and implementation of preconception care.

PMID- 24091887
TI  - Type 2 diabetes and the risk of colorectal adenomas: Black Women's Health Study.
AB  - Evidence for the association of type 2 diabetes mellitus (DM) with colorectal
      neoplasms is contradictory, and African Americans have been underrepresented in
      the studies published to date. In a nested case-control study (1995-2009), we
      examined DM and insulin therapy as risk factors for colorectal adenomas in
      African American women enrolled in the ongoing Black Women's Health Study. From
      women reporting ever having undergone a gastrointestinal endoscopy, 917 cases of
      colorectal adenoma were compared with 2,751 controls without a colorectal polyp,
      matched on age and follow-up time. Cases were verified by medical record review.
      We used multivariable logistic regression analyses that included DM exposures and
      selected confounders. There were no overall associations between DM and adenoma
      risk or between insulin use and adenoma risk. However, DM without insulin use was
      inversely associated with risk of colon adenomas (odds ratio (OR) = 0.71, 95%
      confidence interval (CI): 0.52, 0.97) but not rectal adenomas. DM was inversely
      associated with adenoma risk in women older than 55 years (OR = 0.64, 95% CI:
      0.44, 0.91) but not in women 55 years or younger (OR = 1.24, 95% CI: 0.81, 1.89).
      Future research should attempt to replicate the unexpected inverse association of
      DM with colon adenoma risk among older African American women.

PMID- 24091888
TI  - Dynamics of pneumococcal transmission in vaccine-naive children and their HIV
      infected or HIV-uninfected mothers during the first 2 years of life.
AB  - Pneumococcal vaccine-naive mother-child dyads in South Africa had nasopharyngeal
      swabs taken 9 times within the first 2 years of the children's lives between
      January 2007 and May 2009. To quantify the strength of the association of
      serotype-specific carriage in mother-child dyads, a stochastic transmission model
      was fitted to the data. Children were more susceptible to individual serotypes
      included in the 7-valent pneumococcal conjugate vaccine (PCV7) transmitted by
      their mothers than vice versa; however, children infected their mothers with
      these serotypes more frequently than mothers infected children. The child-to
      mother steady-state forces of pneumococcal acquisition were between 0.36 and 3.29
      (per 1,000 days) compared with 0.06-0.51 for mother-to-child transmission.
      Although children of mothers infected with human immunodeficiency virus were more
      often exposed to PCV7 serotypes by their mothers, their risk of acquisition
      remained low compared with the risk of child-to-mother transmission. Mothers
      acquired pneumococci at lower rates (per 1,000 days) from unmeasured exposure
      within families and in the wider community (range, 0.12-1.69 per 1,000 days) than
      did children (range, 1.10-5.21 per 1,000 days). Pneumococcal immunization of
      young children is expected to have an indirect effect of reducing PCV7 serotype
      maternal colonization and possibly disease even in settings such as ours, in
      which there is a high prevalence of human immunodeficiency virus-infected
      mothers. 

PMID- 24091889
TI  - Dietary carbohydrate intake, glycemic index, and glycemic load and endometrial
      cancer risk: a prospective cohort study.
AB  - Endometrial cancer risk has been directly associated with glycemic load. However,
      few studies have investigated this link, and the etiological role of specific
      dietary carbohydrate components remains unclear. Our aim was to investigate
      associations of carbohydrate intake, glycemic index, and glycemic load with
      endometrial cancer risk in the US Prostate, Lung, Colorectal and Ovarian Cancer
      Screening Trial. Recruitment took place in 1993-2001. Over a median of 9.0 years
      of follow-up through 2009, 386 women developed endometrial cancer among 36,115
      considered in the analysis. Dietary intakes were assessed using a 124-item diet
      history questionnaire. Cox proportional hazards models were applied to calculate
      hazard ratios and 95% confidence intervals. Significant inverse associations were
      detected between endometrial cancer risk and total available carbohydrate intake
      (hazard ratio (HR) = 0.66, 95% confidence interval (CI): 0.49, 0.90), total
      sugars intake (HR = 0.71, 95% CI: 0.52, 0.96), and glycemic load (HR = 0.63, 95%
      CI: 0.46, 0.84) when women in the highest quartile of intake were compared with
      those in the lowest. These inverse associations were strongest among overweight
      and obese women. No associations with endometrial cancer risk were observed for
      glycemic index or dietary fiber. Our findings contrast with previous evidence and
      suggest that high carbohydrate intakes and glycemic loads are protective against
      endometrial cancer development. Further clarification of these associations is
      warranted.

PMID- 24091890
TI  - Family caregiving and all-cause mortality: findings from a population-based
      propensity-matched analysis.
AB  - Previous studies have provided conflicting evidence on whether being a family
      caregiver is associated with increased or decreased risk for all-cause mortality.
      This study examined whether 3,503 family caregivers enrolled in the national
      Reasons for Geographic and Racial Differences in Stroke (REGARDS) Study showed
      differences in all-cause mortality from 2003 to 2012 compared with a propensity
      matched sample of noncaregivers. Caregivers were individually matched with 3,503
      noncaregivers by using a propensity score matching procedure based on 15
      demographic, health history, and health behavior covariates. During an average 6
      year follow-up period, 264 (7.5%) of the caregivers died, which was significantly
      fewer than the 315 (9.0%) matched noncaregivers who died during the same period.
      A proportional hazards model indicated that caregivers had an 18% reduced rate of
      death compared with noncaregivers (hazard ratio = 0.823, 95% confidence interval:
      0.699, 0.969). Subgroup analyses by race, sex, caregiving relationship, and
      caregiving strain failed to identify any subgroups with increased rates of death
      compared with matched noncaregivers. Public policy and discourse should recognize
      that providing care to a family member with a chronic illness or disability is
      not associated with increased risk of death in most cases, but may instead be
      associated with modest survival benefits for the caregivers. 

PMID- 24091891
TI  - The relationship of mental and behavioral disorders to all-cause mortality in a
      27-year follow-up of 4 epidemiologic catchment area samples.
AB  - Subjects from the Epidemiologic Catchment Area Program, interviewed during 1979
      1983, were linked to data in the National Death Index through 2007 to estimate
      the association of mental and behavioral disorders with death. There were more
      than 25 years of follow-up for 15,440 individuals, with 6,924 deaths amounting to
      307,881 person-years of observation. Data were analyzed by using age as the time
      scale and parametric approaches to quantify the years of life lost due to
      disorders. Alcohol, drug use, and antisocial personality disorders were
      associated with increased risk of death, but there was no strong association with
      mood and anxiety disorders. Results of high- and low-quality matches with the
      National Death Index were similar. The 3 behavioral disorders were associated
      with 5-15 years of life lost, estimated along the life course via the generalized
      gamma model. Regression tree analyses showed that risk of death was associated
      with alcohol use disorders in nonblacks and with drug disorders in blacks. Phobia
      interacted with alcohol use disorders in nonblack women, and obsessive-compulsive
      disorder interacted with drug use disorders in black men. Both of these anxiety
      disorders were associated with lower risk of death early in life and higher risk
      of death later in life.

PMID- 24091892
TI  - Efficacy and safety of advanced renal cell carcinoma patients treated with
      sorafenib: roles of cytokine pretreatment.
AB  - BACKGROUND: We conducted a retrospective, questionnaire-based analysis to assess
      the outcomes of advanced renal cell carcinoma (RCC) in Japanese patients treated
      with sorafenib in the daily clinical setting. PATIENTS AND METHODS: Patients (n =
      110) were treated with sorafenib 400 mg twice daily at 12 centers. Overall
      survival (OS), progression-free survival (PFS), safety, and prognostic factors
      associated with PFS were assessed. RESULTS: The median OS was not reached within
      the study period, while the median PFS was 11.0 mo [95 % confidence interval
      (CI), 6.6 to 14.4 mo]. Univariate analysis showed that higher C-reactive protein
      (CRP) level, lower Na(+) level, and presence of liver metastasis were significant
      predictors of poorer PFS (p < 0.05, respectively). Among these variables,
      multivariate analysis identified higher CRP level (p = 0.004) and the presence of
      liver metastasis (p < 0.001) as being significantly associated with poorer PFS.
      The most common adverse event was skin toxicity (67 %), followed by
      gastrointestinal symptoms (26 %), hypertension (22 %), fatigue (19 %),
      hematological toxicity (10 %), and hemorrhage (6 %). The incidence of adverse
      events was comparable to that of previously reported clinical trials.
      CONCLUSIONS: Multivariate analysis indicated that CRP and liver metastasis were
      negatively associated with prognosis. Sorafenib therapy for Japanese patients
      with advanced RCC was effective and well tolerated.

PMID- 24091893
TI  - 1H, 15N, and 13C resonance assignment of cerato-populin, a fungal PAMP from
      Ceratocystis populicola.
AB  - Plant pathogenic fungi secrete several non-catalytic proteins involved in various
      aspects of the pathogenesis process. Amongst these, cerato-populin (Pop1)
      produced by Ceratocystis populicola; a protein orthologous of cerato-platanin
      (CP), the core member of the CP family. These two proteins interact with host and
      non-host plants. In plane leaves they induce synthesis of phytoalexins,
      disruption of intercellular and intracellular leaf tissue, cell plasmolysis,
      programmed cell death, over-expression of defence-related genes, H2O2 and NO
      production, activation of MAPK cascade and plant resistance. All these features
      point to CP and Pop1 as defence inducers, though Pop1 shows a reduced efficiency.
      Pop1/CP similarity is 73%. CD spectroscopy highlights some secondary structure
      differences between Pop1 and CP. Indeed, the region between the first two
      cysteines (C20-C57), that in CP includes the beta2-strand and it is involved in
      GlcNAc (N-acetyl-D-glucosamine) interaction, in Pop1 is predicted to be fully
      disordered.

PMID- 24091894
TI  - Production of anthraquinones, phenolic compounds and biological activities from
      hairy root cultures of Polygonum multiflorum Thunb.
AB  - Polygonum multiflorum Thunb. is a highly important medicinal plant producing
      anthraquinones (emodin and physcion) and phenolic compounds which has
      pharmaceutical use. In vitro seedling explants such as roots, internodals, nodals
      and leaves were inoculated with A. rhizogenes strain KCTC 2703. Transformed roots
      were induced from internodals and leaf explants. Six transgenic clones of hairy
      roots were established and confirmed by polymerase chain reaction (PCR) and
      reverse transcription-PCR (RT-PCR) using rolC specific primers. Hairy roots
      cultured using MS liquid medium supplemented with 30 g/l sucrose showed highest
      accumulation of biomass (99.05 g/l FW [fresh weight] and 10.95 g/l DW [dry
      weight]) and highest production of anthraquinones content (emodin 211.32 MUg/g DW
      and physcion 353.23 MUg/g DW) were observed at 20 days. Nearly 9.5-fold increment
      of biomass was evident in suspension cultures at 20 days of culture and hairy
      root biomass produced in suspension cultures possessed 3.7- and 3.5-fold higher
      content of emodin and physcion, respectively, when compared with the
      untransformed control roots. MS basal liquid medium was superior for the growth
      of hairy roots and production of anthraquinones compared with other culture media
      evaluated (SH, B5 and N6), with MS-basal liquid medium supplemented with 30 g/l
      sucrose was optimal for secondary metabolite production. A total of 23
      polyphenolic compounds were identified and quantified from P. multiflorum
      untransformed and hairy roots, which includes hydroxybenzoic acids,
      hydroxycinnamic acids, flavonols and other groups of phenolic compounds. The
      ultra-performance liquid chromatography (UPLC) analysis of the phenolic compounds
      profile revealed that pyrogallol, hesperidin, naringenin and formononetin were
      higher in hairy roots compared to untransformed roots. The total phenolics,
      flavonoids content, antioxidant and antimicrobial activity was high in hairy
      roots compared to untransformed roots. This is the first report for the
      production of anthraquinones (emodin and physcion), phenolic compounds and
      biological activities from hairy root cultures of P. multiflorum. 

PMID- 24091895
TI  - The nitrate reductase inhibitor, tungsten, disrupts actin microfilaments in Zea
      mays L.
AB  - Tungsten is a widely used inhibitor of nitrate reductase, applied to diminish the
      nitric oxide levels in plants. It was recently shown that tungsten also has heavy
      metal attributes. Since information about the toxic effects of tungsten on actin
      is limited, and considering that actin microfilaments are involved in the entry
      of tungsten inside plant cells, the effects of tungsten on them were studied in
      Zea mays seedlings. Treatments with sodium tungstate for 3, 6, 12 or 24 h were
      performed on intact seedlings and seedlings with truncated roots. Afterwards,
      actin microfilaments in meristematic root and leaf tissues were stained with
      fluorescent phalloidin, and the specimens were examined by confocal laser
      scanning microscopy. While the actin microfilament network was well organized in
      untreated seedlings, in tungstate-treated ones it was disrupted in a time
      dependent manner. In protodermal root cells, the effects of tungsten were
      stronger as cortical microfilaments were almost completely depolymerized and the
      intracellular ones appeared highly bundled. Fluorescence intensity measurements
      confirmed the above results. In the meristematic leaf tissue of intact seedlings,
      no depolymerization of actin microfilaments was noticed. However, when root tips
      were severed prior to tungstate application, both cortical and endoplasmic actin
      networks of leaf cells were disrupted and bundled after 24 h of treatment. The
      differential response of root and leaf tissues to tungsten toxicity may be due to
      differential penetration and absorption, while the effects on actin
      microfilaments could not be attributed to the nitric oxide depletion by tungsten.

PMID- 24091897
TI  - Hierarchy of gene expression data is predictive of future breast cancer outcome.
AB  - We calculate measures of hierarchy in gene and tissue networks of breast cancer
      patients. We find that the likelihood of metastasis in the future is correlated
      with increased values of network hierarchy for expression networks of cancer
      associated genes, due to the correlated expression of cancer-specific pathways.
      Conversely, future metastasis and quick relapse times are negatively correlated
      with the values of network hierarchy in the expression network of all genes, due
      to the dedifferentiation of gene pathways and circuits. These results suggest
      that the hierarchy of gene expression may be useful as an additional biomarker
      for breast cancer prognosis. 

PMID- 24091896
TI  - Evaluation and management of the premenopausal woman with low BMD.
AB  - Interpretation of bone mineral density (BMD) results in premenopausal women is
      particularly challenging, since the relationship between BMD and fracture risk is
      not the same as for postmenopausal women. In most cases, Z scores rather than T
      scores should be used to define "low BMD" in premenopausal women. The finding of
      low BMD in a premenopausal woman should prompt thorough evaluation for secondary
      causes of bone loss. If a secondary cause is found, management should focus on
      treatment of this condition. In a few cases where the secondary cause cannot be
      eliminated, treatment with a bone active agent to prevent bone loss should be
      considered. In women with no fractures and no known secondary cause, low BMD is
      associated with microarchitectural defects similar to young women with fractures;
      however, no longitudinal data are available to allow use of BMD to predict
      fracture risk. BMD is likely to be stable in these women with isolated low BMD,
      and pharmacologic therapy is rarely necessary. Assessment of markers of bone
      turnover and follow-up bone density measurements can help to identify those with
      an ongoing process of bone loss that may indicate a higher risk for fracture, and
      possible need for pharmacologic intervention. 

PMID- 24091898
TI  - Three-dimensional imaging of crystalline inclusions embedded in intact maize
      stalks.
AB  - Mineral inclusions in biomass are attracting increased scrutiny due to their
      potential impact on processing methods designed to provide renewable feedstocks
      for the production of chemicals and fuels. These inclusions are often sculpted by
      the plant into shapes required to support functional roles that include the
      storage of specific elements, strengthening of the plant structure, and providing
      a defense against pathogens and herbivores. In situ characterization of these
      inclusions faces substantial challenges since they are embedded in an opaque,
      complex polymeric matrix. Here we describe the use of Bragg coherent diffraction
      imaging (BCDI) to study mineral inclusions within intact maize stalks. Three
      dimensional BCDI data sets were collected and used to reconstruct images of
      mineral inclusions at 50-100 nm resolution. Asymmetries in the intensity
      distributions around the Bragg peaks provided detailed information about the
      deformation fields within these crystal particles revealing lattice defects that
      result in distinct internal crystal domains.

PMID- 24091899
TI  - Extrascleral spread of choroidal melanoma via tantalum marker suture track.

PMID- 24091900
TI  - Preanesthesia medical evaluation for electroconvulsive therapy: a review of the
      literature.
AB  - OBJECTIVE: Electroconvulsive therapy (ECT) is widely used for the treatment of
      psychiatric disorders, yet there is few published literature to guide the
      practitioner in the preprocedural evaluation of patients. Based on a review of
      the literature, we sought to develop a concise, algorithmic approach to be used
      when evaluating patients for ECT, including those with underlying conditions,
      such as cardiovascular and neurological disorders. METHODS: The databases of Ovid
      MEDLINE, PubMed, the Web of Knowledge, and PsychINFO were searched from January
      2000 through December 2011. All abstracts were reviewed for relevancy to
      preprocedural ECT evaluation, and full articles of selected abstracts were
      reviewed in full, along with bibliographies of each. Algorithms were then
      constructed using the clinical information obtained from the selected articles.
      RESULTS: Our review of the literature located 275 articles using the search
      criteria. After review, 38 articles were selected. A total of 167 articles were
      excluded because they did not pertain to medical comorbidities in patients
      undergoing ECT, and an additional 70 were excluded because they did not pertain
      to ECT. Bibliography review of the selected articles located an additional 10
      articles. CONCLUSIONS: Although ECT is generally a safe and effective therapy,
      some patient subgroups, such as those with certain cardiac conditions or history
      of cerebrovascular disease, require additional evaluation or, rarely,
      postponement of ECT. Chronic medical conditions should be optimized before
      undergoing ECT. Most patient populations are able to undergo ECT safely and
      effectively.

PMID- 24091902
TI  - Comparing effects of ketamine and thiopental administration during
      electroconvulsive therapy in patients with major depressive disorder: a
      randomized, double-blind study.
AB  - OBJECTIVES: Recently, ketamine has attracted attention for induction of
      anesthesia during electroconvulsive therapy (ECT). This study compared the
      effects of thiopental and ketamine in patients undergoing this procedure. METHOD:
      This randomized, double-blind clinical trial included inpatients, with major
      depressive disorder, undergoing ECT. Subjects were randomly allocated to receive
      either ketamine or thiopental. Mini-Mental State Examination and Hamilton
      Depression Rating Scale were used to assess memory and depression, respectively,
      before the first and second ECT sessions as well as a few days and 1 month after
      the sixth session. The electrical charge, seizure duration, blood pressure, and
      heart rate were also recorded. RESULTS: Of the 31 patients, 17 met the criteria
      for the ketamine group but 2 dropped out of the study. Therefore, 15 patients
      received ketamine and 14 received thiopental. Each patient underwent 6 ECT
      sessions. At the end of the study, depression improved significantly in both
      groups. However, a significant difference in depression improvement was noted
      only before the second ECT with ketamine compared with thiopental. Despite a
      significant decline in Mini-Mental State Examination scores in both groups after
      the first ECT, cognitive function improved afterward but was only significant in
      ketamine group. Seizure duration was found to be significantly longer with
      ketamine. Stimulus intensity used for each ECT increased gradually and linearly
      with a greater increase observed in thiopental group. CONCLUSIONS: Ketamine
      administration during ECT is well tolerated and patients may experience earlier
      improvement in depressive symptoms, longer seizure duration, and better cognitive
      performance when compared with thiopental.

PMID- 24091903
TI  - The role of ECT in suicide prevention.
AB  - Suicide is a leading cause of death among psychiatric patients, and a leading
      cause of death from all causes in people younger than 30 years. The rapid relief
      of severe depression, mania, and psychosis by electroconvulsive therapy (ECT) is
      accompanied by the rapid reduction in suicide drive. Electroconvulsive therapy
      use is, however, inhibited by fear of electricity, unreasoned prejudice,
      legislative restrictions, and the limited availability of trained professionals
      and adequate facilities. This review assesses the experience with ECT in persons
      with suicide risk and recommends the consideration of ECT in treatment algorithms
      to reduce suicide rates. 

PMID- 24091905
TI  - Particle size dependent confinement and lattice strain effects in LiFePO4.
AB  - We report the intrinsic electronic properties of LiFePO4 (LFP) with different
      particle sizes measured by broad-band impedance spectroscopy and diffuse
      reflectance spectroscopy. The electronic properties show typical size-dependent
      effects with decreasing particle size (up to 150 nm). However, at the nanoscale
      level, we observed an enhancement in the polaronic conductivity about an order of
      magnitude. We found that the origin of the enhanced electronic conductivity in
      LFP is due to the significant lattice strain associated with the reduction of
      particle size. The observed lattice strain component corresponds to the
      compressive part which leads to a decrease in the hopping length of the polarons.
      We reproduce nonlinearities in the transport properties of LFP with particle
      size, to capture the interplay between confinement and lattice strain, and track
      the effects of strain on the electron-phonon interactions. These results could
      explain why nano-sized LFP has a better discharge capacity and higher rate
      capability than the bulk counterpart. We suggest that these new correlations will
      bring greater insight and better understanding for the optimization of LFP as a
      cathode material for advanced lithium ion batteries. 

PMID- 24091904
TI  - Highly sensitive and selective fluorescent detection of cerebral lead(II) based
      on graphene quantum dot conjugates.
AB  - A novel probe based on graphene quantum dot conjugates was developed for
      fluorescent detection of Pb(2+) (LOD: 9 pM) and furthermore for monitoring Pb(2+)
      in the striatum of rat, combined with microdialysis sampling in vivo. 

PMID- 24091906
TI  - Factors affecting the magnetic coupling in Sr2V3O9 type oxides: As for V
      substitution in the VO4 tetrahedra and nature of the cation.
AB  - A density functional theory study of the magnetic couplings in Sr2V3O9 type
      magnetic oxides suggests that whereas the intrachain coupling is always weakly
      ferromagnetic, the interchain coupling may be antiferromagnetic or even weakly
      ferromagnetic depending on the nature of the central tetrahedral atom (As/V)
      cations, and, to a lesser extent, structural details. 

PMID- 24091907
TI  - Serologic markers associated with development of Crohn's disease after ileal
      pouch anal anastomosis for ulcerative colitis.
AB  - BACKGROUND AND AIMS: One of the causes of pouch failure after ileal pouch anal
      anastomosis (IPAA) for ulcerative colitis (UC) is the development of de novo
      Crohn's disease (CD). Our aim was to clearly define factors associated with post
      IPAA CD. METHODS: We conducted a cross-sectional study to compare demographic,
      clinical, and serological characteristics of patients with and without post-IPAA
      CD. All subjects underwent testing for anti-neutrophil cytoplasm antibodies, anti
      Saccaromyces cerevisiae antibodies, anti-outer membrane porin C antibodies, and
      anti-CBir1 flagellin (anti-CBir1). A multivariable model assessed factors
      associated with post-IPAA CD. RESULTS: Thirty-nine subjects were enrolled in the
      study: 20 cases and 19 controls. Patients who developed post-IPAA CD were
      significantly younger (median 22 +/- 9.9 vs. 30 +/- 11.3, p = .027) at the time
      of UC diagnosis and exhibited more extraintestinal manifestations compared to
      controls (p = .023). No significant difference between the groups was found with
      respect to family history, smoking, duration of illness prior to colectomy, time
      to the onset of pouchitis, preoperative treatment, and indication for surgery.
      However, the post-operative serologic profile differed significantly with far
      more cases having elevated anti-CBir1 titers (p = .016, OR 8.81), the latter
      being the only independent predictor in the combined model. CONCLUSIONS: Patients
      with Crohn's disease of the pouch were more likely to have elevated CBir1
      antibodies titers than those with simple pouchitis and healthy pouches. The
      stability of the CBir1 antibodies (pre- and post-colectomy) must be further
      assessed to establish its value as an independent predictor for development of
      post-IPAA CD.

PMID- 24091908
TI  - Sorafenib treatment is save and may affect survival of recurrent hepatocellular
      carcinoma after liver transplantation.
AB  - INTRODUCTION: Recurrent hepatocellular carcinoma (HCC) after liver
      transplantation (LT) is a rare but challenging condition. In most cases, the
      recurrent tumor is presented with extrahepatic spread. Therefore, systemic
      treatment with sorafenib has to be assessed. Because of a plethora of possible
      drug interactions, e.g., with immunosuppressant or anti-infective therapy, safety
      and feasibility of sorafenib treatment requires special attention. MATERIALS AND
      METHODS: We retrospectively analyzed 18 patients who suffered from recurrent
      advanced HCC after LT between January 2002 and December 2010 at the University
      Hospital Heidelberg regarding safety of sorafenib treatment and survival.
      RESULTS: Results showed that 8 patients were eligible for treatment with
      sorafenib showing a median time to progression (TTP) of 4.5 months and an overall
      survival of 9 months. Most common side effects were grades I and II diarrhea and
      hand-foot syndrome (HFS) which could be managed by sorafenib dose reduction. No
      grade III or IV adverse events (AEs) were noticed. No patient had to discontinue
      treatment due to AEs. The ten patients not amenable for sorafenib treatment, due
      to initial poor performance status or its deterioration after first line
      treatment, were treated with surgical resection (n = 3), locoregional therapies
      (n = 1), or palliative radiation therapy (n = 1). They showed a median overall
      survival of 2.3 months. CONCLUSION: Sorafenib may represent a therapeutic option
      for recurrent HCC after LT with manageable side effects. The clinical benefit of
      sorafenib in this setting is promising but needs to be confirmed in a prospective
      randomized trial.

PMID- 24091909
TI  - Safety and outcomes following resection of colorectal liver metastases in the era
      of current perioperative chemotherapy.
AB  - BACKGROUND: Preoperative chemotherapy is increasingly utilized in the treatment
      of colorectal liver metastases (CRLM). Although this strategy may improve
      resectability, long-term advantages of preoperative chemotherapy for resectable
      CRLM are less clear. The objective of this study is to report safety and outcomes
      when perioperative chemotherapy is routinely added to surgery for CRLM. METHODS:
      A retrospective review of patients undergoing liver resections for CRLM during
      2003-2011 in single academic oncology center. Demographic data, tumor
      characteristics, chemotherapy, surgical details, complications and survival were
      analyzed. RESULTS: The study included 157 patients that underwent 168 liver
      operations. One hundred eighteen patients (70 %) underwent preoperative
      chemotherapy (75 % oxaliplatin-based). Preoperative portal vein embolization was
      utilized in 16 (10.1 %) patients. Overall survival (OS) was 89, 57, and 27 % at
      1, 3, and 5 years, respectively (median survival-42.8 months). Eleven (7 %)
      patients had repeat resections for liver recurrence. Thirty-day mortality was
      1.26 %, morbidity-24 % (6 %-liver related). Complications were not significantly
      different in patients that had preoperative chemotherapy. On a multivariate
      analysis advanced age and >3 lesions predicted poor OS, while advanced age,
      lesions >5 cm, synchronous lesions, margin-positivity and resection less than
      hepatectomy were associated with decreased DFS. CONCLUSIONS: Our results suggest
      that even with chemotherapy and resection only a subset of patients remain
      disease-free after 5 years. However, even in a high-risk patient with multiple
      lesions, preoperative chemotherapy can be administered safely without apparent
      increase in postoperative complications. Perioperative chemotherapy should be
      considered particularly in patients with multifocal or large lesions, synchronous
      disease and short disease-free interval.

PMID- 24091910
TI  - Obesity increases risk for pouch-related complications following restorative
      proctocolectomy with ileal pouch-anal anastomosis (IPAA).
AB  - PURPOSE: Restorative proctocolectomy with ileal pouch-anal anastomosis (IPAA) is
      the preferred surgical treatment for patients with ulcerative colitis and
      familial adenomatous polyposis. As obesity is becoming more epidemic in surgical
      patients, the aim of this study was to investigate if obesity increases
      complication rates following IPAA. METHODS: This study was conducted as a
      retrospective review of patients undergoing IPAA between January 1990 and April
      2011. Patients were categorized by body mass index (BMI): BMI < 30 (non-obese)
      and BMI >= 30 (obese). Preoperative patient demographics, operative variables,
      and postoperative complications were recorded through chart review. The primary
      outcome studied was cumulative complication rate. RESULTS: A total of 103 non
      obese and 75 obese patients were identified who underwent IPAA. Obese patients
      had an increased rate of overall complications (80 % vs. 64%, p = 0.03),
      primarily accounted for by increased pouch-related complications (61% vs. 26%, p
      < 0.01). In particular, obese patients had more anastomotic/pouch strictures (27%
      vs. 6%, p < 0.01), inflammatory pouch complications (17 % vs. 4%, p < 0.01) and
      pouch fistulas (12% vs. 3%, p = 0.03). In a regression model, obesity remained a
      significant risk factor (odds ratio [OR] = 2.86, p = 0.01) for pouch-related
      complications. CONCLUSIONS: Obesity is associated with an increased risk of
      overall and pouch-related complications following IPAA. Obese patients should be
      counseled preoperatively about these risks accordingly.

PMID- 24091911
TI  - Postoperative complications and survival after gastric cancer surgery in patients
      older than 80 years of age.
AB  - BACKGROUND: This study sought to identify and evaluate the risk factors of
      postoperative complications, prognostic factors, and appropriate surgical
      strategies in elderly patients undergoing surgery for gastric cancer. METHODS:
      The medical records of 396 radical gastrectomies conducted from January 2006 to
      December 2011 were retrospectively reviewed. Surgical results and survival rates
      were assessed for 60 elderly patients (aged >= 80 years) and 336 non-elderly
      patients (aged < 80 years). The study groups were compared with respect to
      clinicopathological findings, surgical outcomes, and survival. RESULTS: Elderly
      patients underwent gastrectomies with shorter operation time, showed less
      extensive lymphadenectomy, and had a significant difference in overall survival
      compared with non-elderly patients, although there was no difference in cause
      specific survival among patients receiving curative resection. No significant
      risk factors affecting postoperative complications were identified in the elderly
      patients. Number of comorbidities (>=2) (HR, 5.30; 95 % CI, 1.11-25.32; P =
      0.037) and TNM stage (>=II) (HR, 12.97; 95 % CI, 1.60-105.38; P = 0.017) were
      identified as independent prognostic factors in the elderly patients receiving
      curative resection. CONCLUSIONS: Age is not an independent prognostic factor for
      patients receiving curative resection for gastric cancer. Multiple comorbidities
      may also influence the prognosis of elderly patients. Careful follow-up would
      improve overall survival for elderly patients.

PMID- 24091912
TI  - Depth of submucosal tumor infiltration and its relevance in lymphatic metastasis
      formation for T1b squamous cell and adenocarcinomas of the esophagus.
AB  - BACKGROUND: Surgery for early esophageal carcinoma has been challenged by less
      invasive endoscopic approaches. Selecting patients in need for surgical
      intervention according to their risk of lymphatic spread is mandatory. OBJECTIVE:
      The aim of this study was to evaluate risk factors for lymphatic metastasis
      formation in T1b esophageal carcinomas. METHODS: Histopathological specimens
      following surgical resection for T1b esophageal carcinomas were reevaluated for
      overall submucosal layer thickness, depth of submucosal tumor infiltration, tumor
      length as well as lymphatic and vascular infiltration. Depth of tumor
      infiltration to overall submucosal thickness was divided in thirds (SM1, SM2, and
      SM3) and factors influencing lymphatic metastasis formation were assessed.
      RESULTS: A total of 67 patients with pT1b tumors were analyzed, including 36
      adenocarcinomas (53.7 %) and 31 squamous cell carcinomas (46.3 %). Lymph node
      involvement was seen in 22.4 % (15/67) patients without significant differences
      between SM1 3/11 (27.3 %), SM2, 4/18 (22.2 %), and SM3 (8/38) (21.8 %) (p =
      0.909) carcinomas. On binomial log-regression models, only lymphangioinvasion and
      tumor length >2 cm was significantly associated with lymph node involvement.
      CONCLUSION: As depth of submucosal tumor infiltration did not correlate with the
      formation of lymph node metastases and in regard of the risk of lymphatic spread
      in these cases, surgical resection is warranted in pT1b carcinomas.

PMID- 24091913
TI  - Overexpressing TNF-alpha in pancreatic ductal adenocarcinoma cells and
      fibroblasts modifies cell survival and reduces fatty acid synthesis via
      downregulation of sterol regulatory element binding protein-1 and activation of
      acetyl CoA carboxylase.
AB  - The effect of tumor necrosis factor-alpha (TNF-alpha) gene delivery has been
      suggested as a potentially useful therapeutic approach to improve the
      chemotherapeutic treatment of patients with pancreatic ductal adenocarcinoma
      (PDA), but the exact mechanism of its action is not clearly understood. In this
      study, we analyzed the expression profile of TNF-alpha in PDA tissue and explored
      its potential role in fatty acid synthase (FAS) regulation in PDA cells and in
      fibroblasts. Quantitative real-time polymerase chain reaction was used to examine
      the expression of TNF-alpha in PDA, matching adjacent tissues, and benign
      lesions. Logistic regression models with robust variance were used to analyze the
      gene expression levels, and Kaplan-Meier survival curves were generated. In
      vitro, we overexpressed the TNF-alpha gene in PDA cells and fibroblasts and
      analyzed its effect on cell survival, migration, and on members of the FAS
      signaling pathway. We also evaluated TNF-alpha effects on a panel of inflammation
      , angiogenesis-, and metastasis-related markers. In the tumor tissue of PDA
      patients, compared with their matched adjacent tissue, expression levels of TNF
      alpha were not statistically different and did not correlate with survival or any
      other examined clinicopathological features. Overexpression of TNF-alpha
      significantly (p < 0.05) reduced PDA and fibroblast cell migration. In PDA cells
      that highly overexpress TNF-alpha, this was associated with a significant
      reduction of FAS mRNA and protein expression levels and significant (p < 0.05)
      reduction of SREBP-1 and ACC mRNA. Reduction of FAS by TNF-alpha was inhibited
      when either SREBP-1 or ACC was knocked down by siRNA. PDA cells and fibroblasts
      that overexpress TNF-alpha displayed differential regulation of several
      inflammation-related markers and reduced levels of metastasis-related genes. Our
      data demonstrate a previously unknown multi-targeted involvement of TNF-alpha in
      PDA lipogenesis and inflammation and metastasis and suggest that intratumoral
      introduction of TNF-alpha may have the potential as a novel therapeutic approach
      in human PDA.

PMID- 24091914
TI  - Improved cone-beam computed tomography in supine and prone breast radiotherapy.
      Surface reconstruction, radiation exposure, and clinical workflow.
AB  - BACKGROUND AND PURPOSE: Cone-beam computerized tomography (CBCT) enables three
      dimensional information of the scanned region and provides soft tissue images
      with good spatial resolution. Our aim was to optimize image acquisition settings
      for prone and supine breast radiotherapy with respect to contour accuracy,
      clinical practicalities, and radiation dose. PATIENTS AND METHODS: CBCT images
      were acquired for both prone and supine anthropomorphic phantoms and a female
      cadaver in supine and prone set-up. CBCT protocols were investigated by altering
      the tube current, exposure time, range of projection views, field of view (FOV),
      and starting angle. For clinical practicalities, the frequency of the use of an
      offset CBCT isocenter was evaluated at 558 205 degrees -CBCTs (37 patients; 13
      prone and 24 supine) and 1272 360 degrees -CBCTs (102 patients; 13 prone and 89
      supine). RESULTS: Prone and supine breast CBCT images acquired with a bowtie
      filter, a small FOV, a range of projection views equaling 180 degrees , a tube
      current of 20 mA and an exposure time of 32 ms, demonstrated adequate contour
      accuracy and an elimination of the offset CBCT isocenter procedure, while this
      occurred in 40.7 % for the old full-rotation protocol. Furthermore a 4.3-fold
      dose reduction was observed for the Computed Tomography Dose Index (CTDIw)
      compared to the preset Chest M20 protocol. CONCLUSION: The established 180
      degrees  protocol demonstrated acceptable contour accuracy, eliminated the CBCT
      isocenter offset procedure and reduced patient radiation exposure.

PMID- 24091915
TI  - [RCT with 5-FU and mitomycin C with 28 fractions of 1.8 Gy external radiotherapy
      remains standard treatment of squamous-cell carcinoma of the anus].

PMID- 24091916
TI  - Successful gene therapy in the RPGRIP1-deficient dog: a large model of cone-rod
      dystrophy.
AB  - For the development of new therapies, proof-of-concept studies in large animal
      models that share clinical features with their human counterparts represent a
      pivotal step. For inherited retinal dystrophies primarily involving photoreceptor
      cells, the efficacy of gene therapy has been demonstrated in canine models of
      stationary cone dystrophies and progressive rod-cone dystrophies but not in large
      models of progressive cone-rod dystrophies, another important cause of blindness.
      To address the last issue, we evaluated gene therapy in the retinitis pigmentosa
      GTPase regulator interacting protein 1 (RPGRIP1)-deficient dog, a model
      exhibiting a severe cone-rod dystrophy similar to that seen in humans. Subretinal
      injection of AAV5 (n = 5) or AAV8 (n = 2) encoding the canine Rpgrip1 improved
      photoreceptor survival in transduced areas of treated retinas. Cone function was
      significantly and stably rescued in all treated eyes (18-72% of those recorded in
      normal eyes) up to 24 months postinjection. Rod function was also preserved (22
      29% of baseline function) in four of the five treated dogs up to 24 months
      postinjection. No detectable rod function remained in untreated contralateral
      eyes. More importantly, treatment preserved bright- and dim-light vision.
      Efficacy of gene therapy in this large animal model of cone-rod dystrophy
      provides great promise for human treatment. 

PMID- 24091917
TI  - Inhibitory effects of baicalin in the early stage of 3T3-L1 preadipocytes
      differentiation by down-regulation of PDK1/Akt phosphorylation.
AB  - Baicalin is a flavonoid derived from the root of Scutellaria baicalensis and
      exhibits a broad spectrum of biological activities including anti-adipogenesis.
      However, the inhibitory role of baicalin in the early stage of 3T3-L1 adipocyte
      differentiation relevant to the signaling up-stream of peroxisome proliferator
      activated receptor-gamma (PPAR-gamma) and CCAAT/enhancer binding proteins
      (C/EBPs) expression is unclear, and is the subject of the present investigation.
      We used 3T3-L1 preadipocytes for adipocyte differentiation, Oil Red-O staining
      for the intracellular lipid accumulation assay, and real-time polymerase chain
      reaction (RT-PCR) for assaying the expression of major adipocyte transcription
      factors. We found that baicalin markedly suppressed the Akt phosphorylation in
      early stage of adipocytes differentiation. In addition, we observed that baicalin
      and LY294002 (as an inhibitor of Akt phosphorylation) significantly inhibited
      adipocyte differentiation by down-regulating several adipocyte-specific
      transcription factors, including PPAR-gamma and C/EBPs in 3T3-L1 preadipocytes.
      Furthermore, we observed that baicalin significantly suppressed the Akt
      phosphorylation by inhibiting phosphoinositide-dependent kinase 1 (PDK1). These
      results indicate that the anti-adipogenesis effect of baicalin involves down
      regulation of major transcription factors in 3T3-L1 adipocyte differentiation
      including PPAR-gamma, C/EBP-beta, and C/EBP-alpha through the down-regulation of
      PDK1/Akt phosphorylation.

PMID- 24091918
TI  - Cell-penetrating fusion peptides OD1 and OD2 interact with Bcr-Abl and influence
      the growth and apoptosis of K562 cells.
AB  - The Bcr-Abl oncoprotein is the cause of chronic myelogenous leukemia (CML).
      Crystal structure analysis suggests that Bcr30-63 is the core of the Bcr-Abl
      oligomerization interface for aberrant kinase activity; however, the precise role
      of other residues of Bcr1-72 excluding Bcr30-63 have not been evaluated. In this
      study, Bcr30-63 was named OD2 and other residues of Bcr1-72 were named OD1.
      Cytoplasmic transduction peptide (CTP) was used to carry molecules into
      cytoplasm. CTP-OD1 and CTP-OD2 fusion peptides were expressed from a cold
      inducible expression system. Our results demonstrated that both fusion peptides
      could localize into the cytoplasm, specifically interact with the Bcr-Abl protein
      and further inhibit growth, induce apoptosis, and decrease the phosphorylation of
      Bcr-Abl in K562 cell lines. However, the viability of THP-1, a Bcr-Abl negative
      cell line, was unaffected. These results suggested that CTP-OD1 and CTP-OD2 may
      be an attractive therapeutic option to inhibit the activation of Bcr-Abl kinase
      in CML.

PMID- 24091919
TI  - Clinical studies of the Research Committee on Intractable Vasculitides, the
      Ministry of Health, Labour and Welfare of Japan.
AB  - In Japan, the Research Committee on Intractable Vasculitides, supported by the
      Ministry of Health, Labour and Welfare, has been promoting basic and clinical
      research on vasculitis since 1972. The present Research Committee on Intractable
      Vasculitides comprises 4 subcommittees under the direction of a Principal
      Investigator: Basic and Pathological Research Subcommittee, Clinical Research
      Subcommittee of Small and Medium-sized Vessel Vasculitis, Clinical Research
      Subcommittee of Large-sized Vessel Vasculitis, and International Cooperation
      Research Subcommittee. Since 2008, 9 nationwide clinical studies for vasculitis
      have been conducted and 8 clinical and basic studies are in progress. 

PMID- 24091920
TI  - [PCR-based diagnosis of mucormycosis in tissue samples].
AB  - Mucormycosis is characterized by a rapid, often fatal progression. Early
      diagnosis of invasive mucormycosis is the key for timely therapeutic intervention
      and improved survival. Contrary to the more prevalent aspergillosis, effective
      antifungal therapy of mucormycosis is mainly limited to amphotericin B. Given the
      importance to guide the timely initiation of amphotericin B and possible surgical
      intervention, rapid and specific identification of fungal hyphae is essential.
      Conventional histopathology depends on abundance and morphology of the fungi as
      well as on the skills of the personnel, and usually shows an accuracy of 80 %.
      PCR assays targeting fungal ribosomal genes to identify Mucorales at least at
      genus level increase sensitivity, allow a rapid identification as well as
      detection of double mold infections. Thus, PCR assays are beneficial to
      complement existing approaches. They are recommended to rapidly specify tissue
      diagnosis and accurate identification of fungi. This will help to guide effective
      therapy and thereby, survival will increase. Retrospective analyses of
      mucormycosis by PCR help to evaluate therapeutic interventions and will optimize
      treatment options. 

PMID- 24091921
TI  - PRIME: impact of previous mental health problems on health-related quality of
      life in women with childbirth trauma.
AB  - We investigated the impact of pre-existing mental ill health on postpartum
      maternal outcomes. Women reporting childbirth trauma received counselling
      (Promoting Resilience in Mothers' Emotions; n = 137) or parenting support (n =
      125) at birth and 6 weeks. The EuroQol Five dimensional (EQ-5D)-measured health
      related quality of life at 6 weeks, 6 and 12 months. At 12 months, EQ-5D was
      better for women without mental health problems receiving PRIME (mean difference
      (MD) 0.06; 95 % confidence interval (CI) 0.02 to 0.10) or parenting support (MD
      0.08; 95 % CI 0.01 to 0.14). Pre-existing mental health conditions influence
      quality of life in women with childbirth trauma. 

PMID- 24091922
TI  - Validation of automatic bone age determination in children with congenital
      adrenal hyperplasia.
AB  - BACKGROUND: Determination of bone age is routinely used for following up
      substitution therapy in congenital adrenal hyperplasia (CAH) but today is a
      procedure with significant subjectivity. OBJECTIVE: The aim was to test the
      performance of automatic bone age rating by the BoneXpert software package in all
      radiographs of children with CAH seen at our clinic from 1975 to 2006. MATERIALS
      AND METHODS: Eight hundred and ninety-two left-hand radiographs from 100 children
      aged 0 to 17 years were presented to a human rater and BoneXpert for bone age
      rating. Images where ratings differed by more than 1.5 years were each rerated by
      four human raters. RESULTS: Rerating was necessary in 20 images and the rerating
      result was closer to the BoneXpert result than to the original manual rating in
      18/20 (90 %). Bone age rating precision based on the smoothness of longitudinal
      curves comprising a total of 327 data triplets spanning less than 1.7 years
      showed BoneXpert to be more precise (P<0.001). CONCLUSION: BoneXpert performs
      reliable bone age ratings in children with CAH.

PMID- 24091923
TI  - Histiocytic necrotizing lymphadenitis (Kikuchi-Fujimoto disease) with CNS
      involvement in a child.
AB  - We describe the case of a 9-year-old boy with encephalitis associated with
      histiocytic necrotizing lymphadenitis (HNL), also known as Kikuchi-Fujimoto
      disease. The child presented with unilateral cervical lymphadenopathy and fever
      that evolved to encephalitis in 3 weeks. Brain MRI showed bilateral temporal lobe
      hyperintense signal on T2 and FLAIR, hyperintense FLAIR signal in the
      periaqueductal gray matter, medial walls of the third ventricle, and mammillary
      bodies, multiple diffusion restriction foci in a central perivascular
      distribution and central perivascular enhancement. The perivascular distribution
      and nodularity of the diffusion restriction seen in this case has not been
      previously reported in HNL encephalitis. 

PMID- 24091925
TI  - BLUEPRINT: mapping human blood cell epigenomes.

PMID- 24091924
TI  - Male androphilia in the ancestral environment. An ethnological analysis.
AB  - The kin selection hypothesis posits that male androphilia (male sexual attraction
      to adult males) evolved because androphilic males invest more in kin, thereby
      enhancing inclusive fitness. Increased kin-directed altruism has been repeatedly
      documented among a population of transgendered androphilic males, but never among
      androphilic males in other cultures who adopt gender identities as men. Thus, the
      kin selection hypothesis may be viable if male androphilia was expressed in the
      transgendered form in the ancestral past. Using the Standard Cross-Cultural
      Sample (SCCS), we examined 46 societies in which male androphilia was expressed
      in the transgendered form (transgendered societies) and 146 comparison societies
      (non-transgendered societies). We analyzed SCCS variables pertaining to ancestral
      sociocultural conditions, access to kin, and societal reactions to homosexuality.
      Our results show that ancestral sociocultural conditions and bilateral and double
      descent systems were more common in transgendered than in non-transgendered
      societies. Across the entire sample, descent systems and residence patterns that
      would presumably facilitate increased access to kin were associated with the
      presence of ancestral sociocultural conditions. Among transgendered societies,
      negative societal attitudes toward homosexuality were unlikely. We conclude that
      the ancestral human sociocultural environment was likely conducive to the
      expression of the transgendered form of male androphilia. Descent systems,
      residence patterns, and societal reactions to homosexuality likely facilitated
      investments in kin by transgendered males. Given that contemporary transgendered
      male androphiles appear to exhibit elevated kin-directed altruism, these findings
      further indicate the viability of the kin selection hypothesis. 

PMID- 24091926
TI  - Severe congenital neutropenia and chronic neutrophilic leukemia: an intriguing
      molecular connection unveiled by oncogenic mutations in CSF3R.

PMID- 24091927
TI  - Light chain amyloidosis: the heart of the problem.

PMID- 24091928
TI  - Pathogen safety of long-term treatments for bleeding disorders: still relevant to
      current practice.

PMID- 24091929
TI  - Advances in myelofibrosis: a clinical case approach.
AB  - Primary myelofibrosis is a member of the myeloproliferative neoplasms, a diverse
      group of bone marrow malignancies. Symptoms of myelofibrosis, particularly those
      associated with splenomegaly (abdominal distention and pain, early satiety,
      dyspnea, and diarrhea) and constitutional symptoms, represent a substantial
      burden to patients. Most patients eventually die from the disease, with a median
      survival ranging from approximately 5-7 years. Mutations in Janus kinase 2
      (JAK2), a kinase that is essential for the normal development of erythrocytes,
      granulocytes, and platelets, notably the V617F mutation, have been identified in
      approximately 50% of patients with myelofibrosis. The approval of a JAK2
      inhibitor in 2011 has improved the outlook of many patients with myelofibrosis
      and has changed the treatment landscape. This article focuses on some of the
      important issues in current myelofibrosis treatment management, including
      differentiation of myelofibrosis from essential thrombocythemia and polycythemia
      vera, up-dated data on the results of JAK2 inhibitor therapy, the role of
      epigenetic mechanisms in myelofibrosis pathogenesis, investigational therapies
      for myelofibrosis, and advances in hematopoietic stem cell transplant. Three
      myelofibrosis cases are included to underscore the issues in diagnosing and
      treating this complex disease. 

PMID- 24091930
TI  - The clinical impact of ponatinib on the risk of bleeding in patients with chronic
      myeloid leukemia.

PMID- 24091931
TI  - Stabilizing nanocrystalline grains in ceramic-oxides.
AB  - Nanocrystalline ceramic-oxides are prone to grain growth rendering their highly
      attractive properties practically unusable. Using atomistic simulations of ceria
      as a model material system, we elucidate a framework to design dopant-pinned
      grain boundaries that prevent this grain growth. While in metallic systems it has
      been shown that a large mismatch between host and dopant atomic sizes prevents
      grain growth, in ceramic-oxides we find that this concept is not applicable.
      Instead, we find that dopant-oxygen vacancy interaction, i.e., dopant migration
      energy in the presence of an oxygen vacancy, and dopant-oxygen vacancy binding
      energy are the controlling factors in grain growth. Our prediction agrees with
      and explains previous experimental observations. 

PMID- 24091932
TI  - Antifibrinolytic Use and Blood Transfusions in Pediatric Scoliosis Surgeries
      Performed at US Children's Hospitals.
AB  - STUDY DESIGN: Retrospective cohort study using the Pediatric Health Information
      Systems database. OBJECTIVE: To determine the association between
      antifibrinolytic use and red cell transfusions in spinal fusion operations
      performed at 37 US Children's Hospitals. SUMMARY OF BACKGROUND DATA: Evidence
      from randomized clinical trials and systematic reviews suggests that
      antifibrinolytic therapy can significantly reduce blood loss in children
      undergoing scoliosis surgery; however, the effectiveness of these agents as used
      in surgeries performed at US children's has not been studied. MATERIALS AND
      METHODS: We included children aged 0-18 years with diagnoses indicating
      adolescent idiopathic scoliosis (AIS) or neuromuscular scoliosis (NMS) for whom a
      spinal fusion procedure was performed between January 1, 2006 and September 30,
      2009. Patients with malignancy, trauma, coagulation disorders, or for whom a cell
      salvage device was employed were excluded. Multilevel logistic regression was
      used to determine associations between epsilon-aminocaproic acid (EACA),
      tranexamic acid (TXA), and aprotinin (APR) use and blood transfusions,
      controlling for patient and surgery characteristics. RESULTS: Cohorts consisted
      of 2722 AIS and 1547 NMS procedures. Antifibrinolytic use varied across hospitals
      (AIS 3.3%, interquartile range, 0%-42%; NMS 12 interquartile range, 0%-46%), and
      was significantly associated with NMS, posterior fusion, number of vertebrae
      fused. Overall, 15% of children received EACA, 7% TXA, and 2% APR. The median
      hospital-specific rate of red cell transfusions was 24% for AIS and 43% for NMS.
      In AIS operations, EACA use, but not TXA use, was associated with significantly
      lower odds of transfusion (odds ratio, 0.42; P<0.001 vs. odds ratio, 1.0; P=0.8).
      In NMS operations, neither EACA nor TXA use was associated with a decrease in
      odds of red cell transfusions. CONCLUSIONS: The effectiveness of
      antifibrinolytics as used outside of clinical trials is unclear and should
      continue to be explored. Future prospective research is needed to evaluate which
      administration protocols will most benefit patients, as well as to determine the
      comparative effectiveness of these drugs in the context of other blood
      conservation strategies.

PMID- 24091933
TI  - Can we always sweep the details of RNA-processing under the carpet?
AB  - RNA molecules follow a succession of enzyme-mediated processing steps from
      transcription to maturation. The participating enzymes, for example the
      spliceosome for mRNAs and Drosha and Dicer for microRNAs, are also produced in
      the cell and their copy-numbers fluctuate over time. Enzyme copy-number changes
      affect the processing rate of the substrate molecules; high enzyme numbers
      increase the processing rate, while low enzyme numbers decrease it. We study
      different RNA-processing cascades where enzyme copy-numbers are either fixed or
      fluctuate. We find that for the fixed enzyme copy-numbers, the substrates at
      steady-state are Poisson-distributed, and the whole RNA cascade dynamics can be
      understood as a single birth-death process of the mature RNA product. In this
      case, solely fluctuations in the timing of RNA processing lead to variation in
      the number of RNA molecules. However, we show analytically and numerically that
      when enzyme copy-numbers fluctuate, the strength of RNA fluctuations increases
      linearly with the RNA transcription rate. This linear effect becomes stronger as
      the speed of enzyme dynamics decreases relative to the speed of RNA dynamics.
      Interestingly, we find that under certain conditions, the RNA cascade can reduce
      the strength of fluctuations in the expression level of the mature RNA product.
      Finally, by investigating the effects of processing polymorphisms, we show that
      it is possible for the effects of transcriptional polymorphisms to be enhanced,
      reduced or even reversed. Our results provide a framework to understand the
      dynamics of RNA processing. 

PMID- 24091935
TI  - Patient activation and 30-day post-discharge hospital utilization.
AB  - BACKGROUND: Patient activation is linked to better health outcomes and lower
      rates of health service utilization. The role of patient activation in the rate
      of hospital readmission within 30 days of hospital discharge has not been
      examined. METHODS: A secondary analysis using data from the Project RED-LIT
      randomized controlled trial conducted at an urban safety net hospital. Data from
      695 English-speaking general medical inpatient subjects were analyzed. We used an
      adapted, eight-item version of the validated Patient Activation Measure (PAM).
      Total scores were categorized, according to standardized methods, as one of four
      PAM levels of activation: Level 1 (lowest activation) through Level 4 (highest
      activation). The primary outcome measure was total 30-day post-discharge hospital
      utilization, defined as total emergency department (ED) visits plus hospital
      readmissions including observation stays. Poisson regression was used to control
      for confounding. RESULTS: Of the 695 subjects, 67 (9.6 %) were PAM Level 1, 123
      (17.7 %) were Level 2, 193 (27.8 %) were Level 3, and 312 (44.9 %) were Level 4.
      Compared with highly activated patients (PAM Level 4), a higher rate of 30-day
      post-discharge hospital utilization was observed for patients at lower levels of
      activation (PAM Level 1, incident rate ratio [IRR] 1.75, 95 % CI,1.18 to 2.60)
      and (PAM Level 2, IRR 1.50, 95 % CI 1.06 to 2.13). The rate of returning to the
      hospital among patients at PAM Level 3 was not statistically different than
      patients with PAM Level 4 (IRR 1.30, 95 % CI, 0.94 to 1.80). The rate ratio for
      PAM Level 1 was also higher compared with Level 4 for ED use alone (1.68(1.07 to
      2.63)) and for hospital readmissions alone (1.93 [1.22 to 3.06]). CONCLUSION:
      Hospitalized adult medical patients in an urban academic safety net hospital with
      lower levels of Patient Activation had a higher rate of post-discharge 30-day
      hospital utilization.

PMID- 24091934
TI  - Activation of AMPK enhances neutrophil chemotaxis and bacterial killing.
AB  - An inability of neutrophils to eliminate invading microorganisms is frequently
      associated with severe infection and may contribute to the high mortality rates
      associated with sepsis. In the present studies, we examined whether metformin and
      other 5' adenosine monophosphate-activated protein kinase (AMPK) activators
      affect neutrophil motility, phagocytosis and bacterial killing. We found that
      activation of AMPK enhanced neutrophil chemotaxis in vitro and in vivo, and also
      counteracted the inhibition of chemotaxis induced by exposure of neutrophils to
      lipopolysaccharide (LPS). In contrast, small interfering RNA (siRNA)-mediated
      knockdown of AMPKalpha1 or blockade of AMPK activation through treatment of
      neutrophils with the AMPK inhibitor compound C diminished neutrophil chemotaxis.
      In addition to their effects on chemotaxis, treatment of neutrophils with
      metformin or aminoimidazole carboxamide ribonucleotide (AICAR) improved
      phagocytosis and bacterial killing, including more efficient eradication of
      bacteria in a mouse model of peritonitis-induced sepsis. Immunocytochemistry
      showed that, in contrast to LPS, metformin or AICAR induced robust actin
      polymerization and distinct formation of neutrophil leading edges. Although LPS
      diminished AMPK phosphorylation, metformin or AICAR was able to partially
      decrease the effects of LPS/toll-like receptor 4 (TLR4) engagement on downstream
      signaling events, particularly LPS-induced IkappaBalpha degradation. The IkappaB
      kinase (IKK) inhibitor PS-1145 diminished IkappaBalpha degradation and also
      prevented LPS-induced inhibition of chemotaxis. These results suggest that AMPK
      activation with clinically approved agents, such as metformin, may facilitate
      bacterial eradication in sepsis and other inflammatory conditions associated with
      inhibition of neutrophil activation and chemotaxis. 

PMID- 24091938
TI  - Bridging molecular clusters and fullerene.
AB  - The monochloro derivative {Pt3}Cl [(1), {Pt3} = Pt3(MU-PBu(t)2)3(CO)2] was
      reacted with one equiv. of 4-ethynylbenzaldehyde under Sonogashira
      dehydrohalogenation conditions to afford {Pt3}CC-(1,4)C6H4-CHO, (3). Under
      analogous conditions, the condensation of the dichloride {Pt6}Cl2 [(2), {Pt6} =
      Pt6(MU-PBu(t)2)4(CO)4] with two equiv. of 4-ethynyl-benzaldehyde provided
      {Pt6}(CC-(1,4)C6H4-CHO)2, (4). The fulleropyrrolidine derivatives {Pt3}CC
      (1,4)C6H4-C2H3N(C8H17)C60, (5), and {Pt6}(CC-(1,4)C6H4-C2H3N(C8H17)C60)2, (6),
      were obtained by reacting the formyl clusters 2 and 4 with an appropriate amount
      of N-octylglycine and C60. Cyclovoltammetric and IR, UV and NIR
      spectroelectrochemical data suggest the absence of a significant communication
      between the cluster and the fullerene units in covalent assemblies 5 and 6. The
      crystal and molecular structure of compound 3 is also reported. 

PMID- 24091936
TI  - Genetic influences on the development of alcoholism.
AB  - Alcoholism has a substantial heritability yet the detection of specific genetic
      influences has largely proved elusive. The strongest findings are with genes
      encoding alcohol metabolizing enzymes. A few candidate genes such as GABRA2 have
      shown robust associations with alcoholism. Moreover, it has become apparent that
      variants in stress-related genes such as CRHR1, may only confer risk in
      individuals exposed to trauma, particularly in early life. Over the past decade
      there have been tremendous advances in large scale SNP genotyping technologies
      allowing for genome-wide associations studies (GWAS). As a result, it is now
      recognized that genetic risk for alcoholism is likely to be due to common
      variants in very many genes, each of small effect, although rare variants with
      large effects might also play a role. This has resulted in a paradigm shift away
      from gene centric studies toward analyses of gene interactions and gene networks
      within biologically relevant pathways. 

PMID- 24091939
TI  - Forces on a saltating grain in air.
AB  - A wind tunnel experiment was performed to measure the trajectories of individual
      sand grains. Then, the acceleration given by the numerical differentiation was
      used to assess the relative importance of different external forces on a
      saltating sand grain in air. It is reconfirmed that the gravitational force and
      drag are the most important to grain motion. The lift also has certain influence.
      However, the present research does not support that the electrostatic force is
      significant. 

PMID- 24091937
TI  - RYR1 mutations as a cause of ophthalmoplegia, facial weakness, and malignant
      hyperthermia.
AB  - IMPORTANCE: Total ophthalmoplegia can result from ryanodine receptor 1 (RYR1)
      mutations without overt associated skeletal myopathy. Patients carrying RYR1
      mutations are at high risk of developing malignant hyperthermia. Ophthalmologists
      should be familiar with these important clinical associations. OBJECTIVE: To
      determine the genetic cause of congenital ptosis, ophthalmoplegia, facial
      paralysis, and mild hypotonia segregating in 2 pedigrees diagnosed with atypical
      Moebius syndrome or congenital fibrosis of the extraocular muscles. DESIGN,
      SETTING, AND PARTICIPANTS: Clinical data including medical and family histories
      were collected at research laboratories at Boston Children's Hospital and Jules
      Stein Eye Institute (Engle and Demer labs) for affected and unaffected family
      members from 2 pedigrees in which patients presented with total ophthalmoplegia,
      facial weakness, and myopathy. INTERVENTION: Homozygosity mapping and whole-exome
      sequencing were conducted to identify causative mutations in affected family
      members. Histories, physical examinations, and clinical data were reviewed. MAIN
      OUTCOME AND MEASURE: Mutations in RYR1. RESULTS: Missense mutations resulting in
      2 homozygous RYR1 amino acid substitutions (E989G and R3772W) and 2 compound
      heterozygous RYR1 substitutions (H283R and R3772W) were identified in a
      consanguineous and a nonconsanguineous pedigree, respectively. Orbital magnetic
      resonance imaging revealed marked hypoplasia of extraocular muscles and
      intraorbital cranial nerves. Skeletal muscle biopsy specimens revealed
      nonspecific myopathic changes. Clinically, the patients' ophthalmoplegia and
      facial weakness were far more significant than their hypotonia and limb weakness
      and were accompanied by an unrecognized susceptibility to malignant hyperthermia.
      CONCLUSIONS AND RELEVANCE: Affected children presenting with severe congenital
      ophthalmoplegia and facial weakness in the setting of only mild skeletal myopathy
      harbored recessive mutations in RYR1, encoding the ryanodine receptor 1, and were
      susceptible to malignant hyperthermia. While ophthalmoplegia occurs rarely in
      RYR1-related myopathies, these children were atypical because they lacked
      significant weakness, respiratory insufficiency, or scoliosis. RYR1-associated
      myopathies should be included in the differential diagnosis of congenital
      ophthalmoplegia and facial weakness, even without clinical skeletal myopathy.
      These patients should also be considered susceptible to malignant hyperthermia, a
      life-threatening anesthetic complication avoidable if anticipated presurgically.

PMID- 24091940
TI  - Effects of ischemic preconditioning on myocardium Caspase-3, SOCS-1, SOCS-3, TNF
      alpha and IL-6 mRNA expression levels in myocardium IR rats.
AB  - The aim of this study was to characterise the effects of ischemic preconditioning
      (IP) on heart function parameters (DeltaST and DeltaT), activities of serum
      creatine kinase (CK), lactate dehydrogenase (LDH), and levels of serum nitric
      oxide (NO), malondialdehyde (MDA), and myocardium Caspase-3 mRNA, SOCS-1, SOCS-3,
      tumor necrosis factor-alpha (TNF-alpha) and interleukin-6 (IL-6) expression
      levels and Apoptosis index in myocardium IR rats. Results showed that DeltaST and
      DeltaST values in IP group were markedly lower than those in IR group. Compared
      with IR group, IP significantly (p < 0.01) decreased serum CK (0.83 +/- 0.09 vs
      1.36 +/- 0.15), LDH (5613 +/- 462 vs 7106 +/- 492) activities and MDA (11.32 +/-
      1.05 vs 15.49 +/- 1.26) level, increased the serum NO (86.39 +/- 7.03 vs 53.77 +/
      4.27) level in IR group. The IP induced a significant decreased in myocardium
      Caspase-3 mRNA (0.303 +/- 0.021 vs 0.515 +/- 0.022) gene expression (p < 0.01)
      compared to IR model group. The IP induced a significant decreased in myocardium
      SOCS-1 (0.241 +/- 0.031 vs 0.596 +/- 0.036), SOCS-3 (0.258 +/- 0.031 vs 0.713 +/-
      0.057), TNF-alpha (0.137 +/- 0.011 vs 0.427 +/- 0.035) and IL-6 (0.314 +/- 0.021
      vs 0.719 +/- 0.064) mRNA gene expression (p < 0.01) compared to IR model group.
      We conclude that IP is effective in the therapy of heart disease. These findings
      may have implications for the clinical development of preconditioning-based
      therapies for ischemic heart disease.

PMID- 24091941
TI  - Human TTC5, a novel tetratricopeptide repeat domain containing gene, activates
      p53 and inhibits AP-1 pathway.
AB  - The transcription factor p53 and AP-1 play an important role in cellular
      proliferation, transformation and death. In this study, we investigated the role
      of a novel human gene, TTC5 (tetratricopeptide repeat domain 5), in the
      regulation of cell signaling pathway and cell viability. TTC5 is a member of the
      TTC family of proteins and has previously been shown to participate in cellular
      stress response. Here we demonstrate for the first time that TTC5 significantly
      activates p53 pathway and inhibits AP-1 transcriptional activity. Further
      investigation revealed that overexpression of TTC5 up-regulated p53 and p21
      expression, and significantly inhibited transcriptional activity, expression and
      phosphorylation of c-Jun. As for the upstream of signaling pathway of AP-1, our
      study demonstrated that overexpression of TTC5 significantly down-regulated the
      expression and phosphorylation of JNK/SAPK. Moreover, overexpression of TTC5
      repressed cell proliferation and induced S phase cell cycle arrest. These results
      indicated that TTC5 may regulate cell viability by p53 and AP-1 signaling
      pathway. 

PMID- 24091942
TI  - cDNA cloning and mRNA expression of retinoid-X-receptor in the ovary of the
      shrimp Metapenaeus ensis.
AB  - Retinoid-X-receptor (RXR) plays an essential role in the molting process of
      decapod crustaceans, by forming a heterodimeric complex with the ecdysteroid
      receptor. However, its role during female reproduction, especially in the process
      of ovarian maturation, has not been characterized. To get an insight into the
      molecular events governing the process of ovarian maturation in shrimps, the full
      length cDNA of RXR from Metapenaeus ensis was cloned by extension of truncated
      cDNA by using the RACE technique. The open reading frame of MeRXR encodes a 410
      amino acid protein with a deduced molecular weight of 44.8 kDa, and putative pI
      of 6.64, which roughly matched our observation from 2DE gel. Phylogenetic
      analysis showed that MeRXR has high similarity to RXR of Penaeus chinensis and P.
      japonicus. RT-PCR revealed that MeRXR was universally expressed in all tissues
      investigated. The variation in MeRXR mRNA expression pattern during ovarian
      maturation was further analyzed by real-time PCR. In contrast to the decrease in
      MeRXR at protein level with ovarian maturation, MeRXR mRNA level was low in pre
      vitellogenic and mid-vitellogenic ovaries, and increased significantly from mid
      vitellogenic to late-vitellogenic stages. This result suggests that MeRXR
      transcripts in the mature ovary probably act as maternal messages for regulating
      early molting events during embryonic development. 

PMID- 24091943
TI  - Interaction between obesity-related genes, FTO and MC4R, associated to an
      increase of breast cancer risk.
AB  - Breast cancer (BC) is a complex disease and obesity is a well-known risk factor
      for its development, especially after menopause. Several studies have shown
      Single Nucleotide Polymorphisms (SNPs) linked to overweight and obesity, such as:
      rs1121980 (T/C) and rs9939609 (A/T) in Fat Mass and Obesity Associated gene (FTO)
      and rs17782313 (T/C) in Melanocortin 4 Receptor gene (MC4R). Thus, we aimed to
      investigate the association between these obesity-related SNPs and BC risk. One
      hundred BC patients and 148 healthy women from Santa Catarina, Brazil entered the
      study. SNPs were genotyped using Taqman assays. For statistical analyses SNPStats
      and SPSS softwares were used. Association analyses were performed by logistic
      regression and were adjusted for age and Body mass index (BMI). Multiple SNPs
      inheritance models (log-additive, dominant, recessive, codominant) were performed
      to determine odds ratios (ORs), assuming 95 % confidence interval (CI) and P
      value = 0.05 as the significance limit. When analyzed alone, FTO rs1121980 and
      rs9939609 did not show significant associations with BC development, however MC4R
      rs17782313 showed increased risk for BC even after adjustments (P-value = 0.032).
      Interestingly, the interaction of FTO and MC4R polymorphisms showed a powerful
      association with BC. We observed a 4.59-fold increased risk for woman who have
      the allele combination C/T/C (FTO rs1121980/FTO rs9939609/MC4R rs17782313) (P
      value = 0.0011, adjusted for age and BMI). We found important and unpublished
      associations between these obesity-related genes and BC risk. These associations
      seem to be independent of their effect on BMI, indicating a direct role of the
      interaction between FTO and MC4R polymorphisms in BC development. 

PMID- 24091944
TI  - Allelic imbalance in 1p, 7q, 9p, 11p, 12q and 16q regions in non-small cell lung
      carcinoma and its clinical association: a pilot study.
AB  - In lung cancer pathogenesis, genetic instability, i.e., loss of heterozygosity
      (LOH) and microsatellite instability (MSI) is a frequent molecular event,
      occurring at an early stage of cancerogenesis. The presence of LOH/MSI in non
      small cell lung carcinoma (NSCLC) was found in many chromosomal regions, but
      exclusive of 3p their diagnostic value remains controversial. In this study we
      focused on other than 3p regions-1p31.2, 7q32.2, 9p21.3, 11p15.5, 12q23.2 and
      16q22-the loci of many oncogenes and tumour suppressor genes. To analyze the
      potential role of LOH/MSI involved in NSCLC pathogenesis we allelotyped a panel
      of 13 microsatellite markers in a group of 56 cancer specimens. Our data
      demonstrate the presence of allelic loss for all (13) analyzed markers. Total
      LOH/MSI frequency in NSCLC was the highest for chromosomal region 11p15.5 (25.84
      %), followed by 9p21.3 and 1p31.2 (19.87 and 16.67 % respectively). A
      statistically significant increase of total LOH/MSI frequency was detected for
      the 11p15.5 region (p = 0.0301; chi(2) test). The associations of total LOH/MSI
      frequency: 1) increase in 11p15.5 region (p = 0.047; chi(2) test) and 2) decrease
      in 7q32.2 region (p = 0.037; chi(2) test) have been statistically significant in
      AJCC III (American Joint Committee on Cancer Staging). In Fractional Allele Loss
      (FAL) index analysis, the correlation with cigarette addiction has been
      statistically significant. The increased amount of cigarettes smoked (pack years)
      in a lifetime correlates with increasing FAL (p = 0.024; Kruskal-Wallis test).
      These results demonstrate that LOH/MSI alternation in studied chromosomal regions
      is strongly influenced by tobacco smoking but do not seem to be pivotal NSCLC
      diagnostic marker with prognostic impact. 

PMID- 24091945
TI  - Electronic health record tools' support of nurses' clinical judgment and team
      communication.
AB  - Nurses need to quickly process information to form clinical judgments,
      communicate with the healthcare team, and guide optimal patient care. Electronic
      health records not only offer potential for enhanced care but also introduce
      unintended consequences through changes in workflow, clinical judgment, and
      communication. We investigated nurses' use of improvised (self-made) and
      electronic health record-generated cognitive artifacts on clinical judgment and
      team communication. Tanner's Clinical Judgment Model provided a framework and
      basis for questions in an online survey and focus group interviews. Findings
      indicated that (1) nurses rated self-made work lists and medication
      administration records highest for both clinical judgment and communication, (2)
      tools aided different dimensions of clinical judgment, and (3) interdisciplinary
      tools enhance team communication. Implications are that electronic health record
      tool redesign could better support nursing work. 

PMID- 24091957
TI  - US government shuts down.

PMID- 24091946
TI  - The Anthropocene could raise biological diversity.

PMID- 24091958
TI  - Geologists take drill to Triassic park.

PMID- 24091959
TI  - Overhauls set scientists on edge.

PMID- 24091960
TI  - Uncertainty on trial.

PMID- 24091961
TI  - Rethinking particle dynamics.

PMID- 24091963
TI  - Astrometry: Europe's star power.

PMID- 24091962
TI  - Pharma scrambles to fast-track drugs.

PMID- 24091964
TI  - Ethics: Taboo genetics.

PMID- 24091968
TI  - Q&A: Textile technologist. Interview by Josie Glausiusz.

PMID- 24091969
TI  - Development: Big data for a sustainable future.

PMID- 24091970
TI  - Reducing emissions: Keep Australia's carbon pricing.

PMID- 24091971
TI  - Carbon emissions: Learn from China's local pilot schemes.

PMID- 24091972
TI  - Health care: Better drug access for terminal patients.

PMID- 24091973
TI  - History: Great scientists and society.

PMID- 24091974
TI  - Materials science: Alloys with long memories.

PMID- 24091975
TI  - Supervolcanoes within an ancient volcanic province in Arabia Terra, Mars.
AB  - Several irregularly shaped craters located within Arabia Terra, Mars, represent a
      new type of highland volcanic construct and together constitute a previously
      unrecognized Martian igneous province. Similar to terrestrial supervolcanoes,
      these low-relief paterae possess a range of geomorphic features related to
      structural collapse, effusive volcanism and explosive eruptions. Extruded lavas
      contributed to the formation of enigmatic highland ridged plains in Arabia Terra.
      Outgassed sulphur and erupted fine-grained pyroclastics from these calderas
      probably fed the formation of altered, layered sedimentary rocks and fretted
      terrain found throughout the equatorial region. The discovery of a new type of
      volcanic construct in the Arabia volcanic province fundamentally changes the
      picture of ancient volcanism and climate evolution on Mars. Other eroded
      topographic basins in the ancient Martian highlands that have been dismissed as
      degraded impact craters should be reconsidered as possible volcanic constructs
      formed in an early phase of widespread, disseminated magmatism on Mars. 

PMID- 24091976
TI  - Three-dimensional imaging of localized surface plasmon resonances of metal
      nanoparticles.
AB  - The remarkable optical properties of metal nanoparticles are governed by the
      excitation of localized surface plasmon resonances (LSPRs). The sensitivity of
      each LSPR mode, whose spatial distribution and resonant energy depend on the
      nanoparticle structure, composition and environment, has given rise to many
      potential photonic, optoelectronic, catalytic, photovoltaic, and gas- and bio
      sensing applications. However, the precise interplay between the three
      dimensional (3D) nanoparticle structure and the LSPRs is not always fully
      understood and a spectrally sensitive 3D imaging technique is needed to visualize
      the excitation on the nanometre scale. Here we show that 3D images related to
      LSPRs of an individual silver nanocube can be reconstructed through the
      application of electron energy-loss spectrum imaging, mapping the excitation
      across a range of orientations, with a novel combination of non-negative matrix
      factorization, compressed sensing and electron tomography. Our results extend the
      idea of substrate-mediated hybridization of dipolar and quadrupolar modes
      predicted by theory, simulations, and electron and optical spectroscopy, and
      provide experimental evidence of higher-energy mode hybridization. This work
      represents an advance both in the understanding of the optical response of noble
      metal nanoparticles and in the probing, analysis and visualization of LSPRs. 

PMID- 24091977
TI  - Enhanced reversibility and unusual microstructure of a phase-transforming
      material.
AB  - Materials undergoing reversible solid-to-solid martensitic phase transformations
      are desirable for applications in medical sensors and actuators, eco-friendly
      refrigerators and energy conversion devices. The ability to pass back and forth
      through the phase transformation many times without degradation of properties
      (termed 'reversibility') is critical for these applications. Materials tuned to
      satisfy a certain geometric compatibility condition have been shown to exhibit
      high reversibility, measured by low hysteresis and small migration of
      transformation temperature under cycling. Recently, stronger compatibility
      conditions called the 'cofactor conditions' have been proposed theoretically to
      achieve even better reversibility. Here we report the enhanced reversibility and
      unusual microstructure of the first martensitic material, Zn45Au30Cu25, that
      closely satisfies the cofactor conditions. We observe four striking properties of
      this material. (1) Despite a transformation strain of 8%, the transformation
      temperature shifts less than 0.5  degrees C after more than 16,000 thermal
      cycles. For comparison, the transformation temperature of the ubiquitous NiTi
      alloy shifts up to 20  degrees C in the first 20 cycles. (2) The hysteresis
      remains approximately 2  degrees C during this cycling. For comparison, the
      hysteresis of the NiTi alloy is up to 70  degrees C (refs 9, 12). (3) The alloy
      exhibits an unusual riverine microstructure of martensite not seen in other
      martensites. (4) Unlike that of typical polycrystal martensites, its
      microstructure changes drastically in consecutive transformation cycles, whereas
      macroscopic properties such as transformation temperature and latent heat are
      nearly reproducible. These results promise a concrete strategy for seeking ultra
      reliable martensitic materials. 

PMID- 24091978
TI  - Unsynchronised subunit motion in single trimeric sodium-coupled aspartate
      transporters.
AB  - Excitatory amino acid transporters (EAATs) are secondary transport proteins that
      mediate the uptake of glutamate and other amino acids. EAATs fulfil an important
      role in neuronal signal transmission by clearing the excitatory neurotransmitters
      from the synaptic cleft after depolarization of the postsynaptic neuron. An
      intensively studied model system for understanding the transport mechanism of
      EAATs is the archaeal aspartate transporter GltPh. Each subunit in the
      homotrimeric GltPh supports the coupled translocation of one aspartate molecule
      and three Na(+) ions as well as an uncoupled flux of Cl(-) ions. Recent crystal
      structures of GltPh revealed three possible conformations for the subunits, but
      it is unclear whether the motions of individual subunits are coordinated to
      support transport. Here, we report the direct observation of conformational
      dynamics in individual GltPh trimers embedded in the membrane by applying single
      molecule fluorescence resonance energy transfer (FRET). By analysing the
      transporters in a lipid bilayer instead of commonly used detergent micelles, we
      achieve conditions that approximate the physiologically relevant ones. From the
      kinetics of FRET level transitions we conclude that the three GltPh subunits
      undergo conformational changes stochastically and independently of each other. 

PMID- 24091980
TI  - Quantum Google in a complex network.
AB  - We investigate the behaviour of the recently proposed Quantum PageRank algorithm,
      in large complex networks. We find that the algorithm is able to univocally
      reveal the underlying topology of the network and to identify and order the most
      relevant nodes. Furthermore, it is capable to clearly highlight the structure of
      secondary hubs and to resolve the degeneracy in importance of the low lying part
      of the list of rankings. The quantum algorithm displays an increased stability
      with respect to a variation of the damping parameter, present in the Google
      algorithm, and a more clearly pronounced power-law behaviour in the distribution
      of importance, as compared to the classical algorithm. We test the performance
      and confirm the listed features by applying it to real world examples from the
      WWW. Finally, we raise and partially address whether the increased sensitivity of
      the quantum algorithm persists under coordinated attacks in scale-free and random
      networks.

PMID- 24091981
TI  - A non-comparative phase II study of dose intensive chemotherapy with doxorubicin
      and ifosfamide followed by high dose ICE consolidation with PBSCT in non
      resectable, high grade, adult type soft tissue sarcomas.
AB  - The objective was to determine the role of dose intensive induction chemotherapy
      in patients with soft tissue sarcomas (STS) that were considered unresectable.
      Treatment consisted of 2-3 cycles of doxorubicin (Dox) and ifosfamide (Ifo)
      followed by high dose chemotherapy with ifosfamide, carboplatin, etoposide (HD
      ICE) plus peripheral blood stem cell transplantation (PBSCT). 30 out of 631
      consecutive patients, median age 46 years (21-62), with high grade STS were
      included. 29 patients completed at least 2 cycles of Dox/Ifo. HD-ICE was withheld
      because of progressive disease (PD) in 5 patients, neurotoxicity in 6 cases,
      insufficient peripheral blood stem cell (PBSC) mobilization, complete remission
      (CR) and refusal in 1 patient each. HD-ICE was associated with non-haematological
      grade III toxicity including emesis, mucositis, fever, neurotoxicity, and
      transaminase level elevation. Two additional patients attained a partial response
      after HD-ICE. Overall, 24 of 30 (80%) patients underwent surgery, with complete
      tumor resections in 19 patients (63% of all patients, 79% of the operated
      subgroup); however, 2 of these required amputation. After a median follow up
      period of 50 months in surviving patients (range, 26-120), 5-year PFS and OS
      rates were 39% and 48%, respectively. Induction chemotherapy plus consolidation
      HD-ICE is generally feasible, but is associated with significant neurotoxicity.
      The advantage of HD-ICE over conventional dose chemotherapy plus external beam
      radiation therapy (EBRT) in non-resectable disease remains unproven.

PMID- 24091982
TI  - Phase I study of sunitinib plus capecitabine/cisplatin or
      capecitabine/oxaliplatin in advanced gastric cancer.
AB  - BACKGROUND: We evaluated the maximum tolerated dose (MTD) and safety of sunitinib
      plus capecitabine/cisplatin (XP) or capecitabine/oxaliplatin (XELOX) in Korean
      patients with advanced gastric cancer (GC). METHODS: Sunitinib (37.5 or 25
      mg/day) was administered on a 2-week-on/1-week-off schedule with chemotherapy.
      Assessments included dose-limiting toxicity (DLT), safety, pharmacokinetics, and
      antitumor activity. RESULTS: Twenty-eight patients received sunitinib/XP; 48
      received sunitinib/XELOX. The MTDs were: sunitinib 25 mg/day, cisplatin 80
      mg/m(2), and capecitabine 1,000 mg/m(2); sunitinib 37.5 mg/day, oxaliplatin 110
      mg/m(2), and capecitabine 800 mg/m(2); and sunitinib 25 mg/day, oxaliplatin 110
      mg/m(2), and capecitabine 1,000 mg/m(2). DLTs at the MTDs comprised grade (G) 4
      febrile neutropenia plus G3 diarrhea (n = 1; sunitinib/XP), dose delays due to
      hematologic toxicity (n = 2; both sunitinib/XP), G3 bleeding (menorrhagia; n = 1;
      sunitinib/XELOX), and G3 increased alanine aminotransferase levels (n = 1;
      sunitinib/XELOX). There was a high frequency of G3/4 hematologic adverse events
      observed with both treatment regimens, particularly with sunitinib/XP. Frequent
      non-hematologic, G3/4 adverse events were nausea, stomatitis, and
      hypophosphatemia with sunitinib/XP and hypophosphatemia and pulmonary embolism
      with sunitinib/XELOX. No drug-drug interactions were apparent. At the MTDs,
      median progression-free survival was 6.4 months and 5.5-8.0 months for
      sunitinib/XP and sunitinib/XELOX, respectively; and the objective response rate
      was 46.7% and 43.5-45.5% for sunitinib/XP and sunitinib/XELOX, respectively.
      CONCLUSIONS: At the MTD, sunitinib/XELOX had an acceptable safety profile in
      patients with advanced GC.

PMID- 24091984
TI  - Psychometric properties of the Japanese version of the Fear-Avoidance Beliefs
      Questionnaire (FABQ).
AB  - BACKGROUND: The Fear-Avoidance Beliefs Questionnaire (FABQ) is useful for
      measuring fear-avoidance beliefs in patients with low back pain (LBP); however,
      no psychometrically validated Japanese version is available. The objective of
      this study was to evaluate reliability and validity of the Japanese version of
      the FABQ for use with Japanese workers with LBP. METHODS: This was conducted as a
      web-based survey. Both confirmatory and exploratory factor analysis were
      performed to examine domain structure of the Japanese version of the FABQ. For
      reliability, internal consistency was assessed with Cronbach's alpha coefficient.
      For concurrent validity, correlation coefficients between the FABQ and the Pain
      Catastrophizing Scale (PCS) were calculated. For known-group validity, the
      relationship between FABQ score and clinical variables such as pain and
      depression was examined. RESULTS: Analyses were based on responses of 1,786 adult
      Japanese workers with LBP. Factor analysis using the principal factor method with
      promax rotation revealed two factors, work and physical activity, in accordance
      with the domain structure of the original version of the scale. For reliability,
      acceptable internal consistency was demonstrated with Cronbach's alpha
      coefficient of 0.882 and 0.783 for each subscale. For concurrent validity,
      significantly moderate correlations were demonstrated between FABQ subscales and
      PCS subscales (r = 0.30-0.39). For known-group validity, as hypothesized,
      significantly higher FABQ subscale scores were observed in workers who had
      stronger pain, who experienced routine work disability with sick leave, who
      experienced recurrence of LBP, and who had depressed mood. CONCLUSIONS: This
      analysis showed that the Japanese version of the FABQ is psychometrically
      reliable and valid to detect fear-avoidance beliefs in Japanese workers with LBP.

PMID- 24091983
TI  - Variants in TNFSF4, TNFAIP3, TNIP1, BLK, SLC15A4 and UBE2L3 interact to confer
      risk of systemic lupus erythematosus in Chinese population.
AB  - Our previous genome-wide association studies on SLE have identified several
      susceptibility genes involved in NF-kappaB signaling pathway, including TNFSF4,
      TNFAIP3, TNIP1, BLK, SLC15A4 and UBE2L3. The aim of this study is to investigate
      the association model (additive, dominant, recessive) of these genes and search
      for possible gene-gene interactions between them. In this study, we explored the
      association model of these six genes and search for possible gene-gene
      interactions based on identified single-nucleotide polymorphisms (SNPs) among
      them by using logistic regression analysis in the combined sample of 4,199 cases
      and 8,255 controls. The most significant association evidence was observed under
      recessive model for all of these SNPs. Besides, significant interactions between
      these SNPs were observed in this study: the TNFSF4 and TNIP1 SNPs (P adjusted =
      1.68E-10), the TNFSF4 and SLC15A4 SNPs (P adjusted = 3.55E-08), the TNFSF4 and
      UBE2L3 SNPs (P adjusted = 8.74E-13), the TNIP1 and BLK SNPs (P adjusted = 9.45E
      10), the TNIP1 and UBE2L3 SNPs (P adjusted = 8.25E-11), the TNFAIP3 and UBE2L3
      SNPs (P adjusted = 3.06E-14) and the BLK and SLC15A4 SNPs (P adjusted = 4.51E
      12). These results may contribute to our understanding of SLE genetic
      interactions and account for the additional risk of certain patients to develop
      SLE.

PMID- 24091985
TI  - Risk factors for acetabular retroversion in developmental dysplasia of the hip:
      does the Pemberton osteotomy contribute?
AB  - BACKGROUND: The purpose of this study was to investigate residual acetabular
      retroversion after skeletal maturity in patients with Pemberton osteotomy.
      PATIENTS AND METHODS: We compared 40 hips in 36 patients treated with a Pemberton
      osteotomy (Pemberton group) and 30 hips in 26 patients treated only with a Pavlik
      harness (Rb group) for developmental dysplasia of the hip. The average age at
      operation in the Pemberton group was 94.5 months and the follow-up duration was
      151.8 months. Radiographic parameters included the acetabular index (alpha angle)
      and the center-edge angle of Wiberg, preoperatively and at skeletal maturity. We
      examined the crossover sign (COS) at the latest follow-up as a sign of acetabular
      retroversion (AR). We compared the parameters between the two groups and examined
      the risk factors for acetabular retroversion using a multivariate Cox model.
      RESULT: A COS (+) was significantly more frequent in the Pemberton group compared
      to the Rb group [15 hips (37.5%) vs 3 hips (10%); p = 0.0077]. In the Pemberton
      group, the average age at operation in COS (+) hips was significantly older than
      that in COS (-) hips (126.9 vs 72.8 months; p = 0.0005). The preoperative alpha
      angle did not vary between hips with and without COS; however, the postoperative
      alpha angle was significantly smaller in COS (+) hips. A multiple logistic
      regression analysis for prediction of COS (+) showed that the age at operation
      and the amount change of alpha angle were significant predictors for COS (+)
      hips. The cut-off of the age at operation was 7 years and 9 months old.
      CONCLUSIONS: AR was present in 37.5% of the hips in the Pemberton group after
      skeletal maturity. Remodeling of acetabular version was observed in younger
      patients; however, hips in older patients (>8 years) at the time of operation and
      greater degrees of correction tended to result in AR.

PMID- 24091986
TI  - Usefulness of intraoperative three-dimensional imaging in fracture surgery: a
      prospective study.
AB  - BACKGROUND: Since its introduction, intraoperative three-dimensional (3D) imaging
      has enabled the analysis of articular fractures and implant positions during
      fracture surgery. The purpose of this study was to evaluate the usefulness of
      intraoperative 3D imaging in locating anatomic structures, correcting errors, and
      preventing revision surgery. METHODS: Between March 2010 and November 2012,
      intraoperative 3D imaging was used during surgery for 109 fractures in 101
      patients. Fluoroscopy was performed with the Iso-C3D (Siemens, Erlangen,
      Germany). We recorded the number of intraoperative revisions for adjustment of
      fracture reduction and correction of implant position for these fractures.
      RESULTS: Cases comprised intra-articular fractures (55%), disruptions of the
      posterior pelvic ring (33%), and syndesmotic injury (12%). The intraoperative
      revision rate was 9.2% (10/109). When considered by fracture site, the revision
      rate was highest for syndesmotic injury (23.1%), followed by iliosacral fixation
      (8.3%) and intra-articular fractures (6.6 %). We changed the implant position in
      six cases, corrected the articular reduction in one case, and revised the
      malreduction of syndesmosis in three cases. No postoperative infection occurred
      in any of these cases. CONCLUSIONS: Intraoperative 3D imaging is useful for
      correcting errors and may prevent a second operation. Three-dimensional imaging
      may be especially helpful in intra-articular fractures, iliosacral screw
      fixation, and syndesmotic injury.

PMID- 24091988
TI  - Nonbactericidal secreted phospholipase A2s are potential anti-inflammatory
      factors in the mammary gland.
AB  - The recent burst of duplication and divergence of the bovine PLA2G2D genes is
      considered typical of immune response genes, and it was recently shown that
      PLA2G2D is abundantly expressed in mouse leukocytes and acts as an
      immunosuppressive phospholipase. Analysis of 1,143 Holstein bulls indicated that
      the four common haplotypes spanning PLA2G2D display copy number variation ranging
      from 1 to 4 per haploid genome. Association of the fourth haplotype with negative
      total merit remained significant (P < 0.002) when corrected for population
      relatedness. We compared the lipase and bactericidal activities of bovine
      pancreatic PLA2G1B with human PLA2G2A and G2D and bovine PLA2G2D1 and G2D4
      proteins, which had been subcloned, expressed, and refolded by us, and the impact
      of point mutations in the calcium binding site was investigated. All tested
      phospholipases were ineffective bactericides of Escherichia coli isolated from
      bovine mastitis. However, in lactating mice treated with E. coli or
      lipopolysaccharide (LPS), intramammary injection of bovine PLA2G1B relieved
      visual and histological inflammation and reduced blood levels of infiltrating
      lactose. Further studies are warranted to determine whether the observed anti
      inflammatory effect involves competitive binding of the receptor Pla2r1 which may
      mimic the LPS resistance effect in Pla2r1-deficient mice. 

PMID- 24091989
TI  - Dynamic heterogeneity of exercising muscle blood flow and O2 utilization.
AB  - Resolving the bases for different physiological functioning or exercise
      performance within a population is dependent on our understanding of control
      mechanisms. For example, when most young healthy individuals run or cycle at
      moderate intensities, oxygen uptake (VO2) kinetics are rapid and the amplitude of
      the VO2 response is not constrained by O2 delivery. For this to occur, muscle O2
      delivery (i.e., blood flow * arterial O2 concentration) must be coordinated
      superbly with muscle O2 requirements (VO2), the efficacy of which may differ
      among muscles and distinct fiber types. When the O2 transport system succumbs to
      the predations of aging or disease (emphysema, heart failure, and type 2
      diabetes), muscle O2 delivery and O2 delivery-VO2 matching and, therefore, muscle
      contractile function become impaired. This forces greater influence of the
      upstream O2 transport pathway on muscle aerobic energy production, and the O2
      delivery-VO2 relationship(s) assumes increased importance. This review is the
      first of its kind to bring a broad range of available techniques, mostly state of
      the art, including computer modeling, radiolabeled microspheres, positron
      emission tomography, magnetic resonance imaging, near-infrared spectroscopy, and
      phosphorescence quenching to resolve the O2 delivery-VO2 relationships and
      inherent heterogeneities at the whole body, interorgan, muscular, intramuscular,
      and microvascular/myocyte levels. Emphasis is placed on the following: 1) intact
      humans and animals as these provide the platform essential for framing and
      interpreting subsequent investigations, 2) contemporary findings using novel
      technological approaches to elucidate O2 delivery-VO2 heterogeneities in humans,
      and 3) future directions for investigating how normal physiological responses can
      be explained by O2 delivery-VO2 heterogeneities and the impact of aging/disease
      on these processes.

PMID- 24091990
TI  - The muscle stretch reflex throughout the menstrual cycle.
AB  - INTRODUCTION: The significant sex disparity in sports-related knee injuries may
      be due to underlying differences in motor control. Although the development of
      sex-specific movement patterns is likely multifactorial, this study specifically
      focuses on the potential modulatory role of sex hormones. PURPOSE: This study
      aimed to investigate the muscle stretch reflex (MSR) across the menstrual cycle.
      We hypothesized that the MSR would fluctuate throughout the menstrual cycle and
      that the lowest response would correspond with peak concentrations of estrogen.
      METHODS: Nineteen healthy women age 18-35 yr participated in this study: 8
      eumenorrheic women and 11 women taking oral contraceptives. Serum estradiol and
      progesterone concentrations, anterior knee laxity (AKL), and the MSR response of
      the quadriceps muscles were measured three times during the menstrual cycle.
      RESULTS: The MSR response of the rectus femoris (RF) varied significantly across
      the menstrual cycle in both groups. Specifically, the RF MSR response was 2.4
      times lower during the periovulatory phase when compared with the luteal phase (P
      = 0.007). The same trend was seen in the vastus medialis, but this did not reach
      statistical significance (P = 0.070). The MSR response of the vastus lateralis
      did not change significantly across the menstrual cycle (P = 0.494). A mixed
      model comparison did not show an association between endogenous concentrations of
      estradiol and progesterone, exposure to hormonal contraceptives or AKL, and the
      MSR response for any muscle. CONCLUSIONS: Our results demonstrate that the RF MSR
      response varies throughout the menstrual cycle with the lowest response around
      the time of ovulation. Additional research is needed to clarify the exact
      relationship between sex hormones, AKL, and MSR response and to determine the
      specific origin of the change along the monosynaptic reflex arc.

PMID- 24091991
TI  - Muscle glycogen content modifies SR Ca2+ release rate in elite endurance
      athletes.
AB  - PURPOSE: The aim of the present study was to investigate the influence of muscle
      glycogen content on sarcoplasmic reticulum (SR) function and peak power output
      (Wpeak) in elite endurance athletes. METHODS: Fourteen highly trained male
      triathletes (VO2max = 66.5 +/- 1.3 mL O2.kg.min), performed 4 h of glycogen
      depleting cycling exercise (HRmean = 73% +/- 1% of maximum). During the first 4 h
      of recovery, athletes received either water (H2O) or carbohydrate (CHO),
      separating alterations in muscle glycogen content from acute changes affecting SR
      function and performance. Thereafter, all subjects received CHO-enriched food for
      the remaining 20-h recovery period. RESULTS: Immediately after exercise, muscle
      glycogen content and SR Ca release rate was reduced to 32% +/- 4% (225 +/- 28
      mmol.kg dw) and 86% +/- 2% of initial levels, respectively (P < 0.01). Glycogen
      markedly recovered after 4 h of recovery with CHO (61% +/- 2% of preexercise) and
      SR Ca release rate returned to preexercise level. However, in the absence of CHO
      during the first 4 h of recovery, glycogen and SR Ca release rate remained
      depressed, with the normalization of both parameters at the end of the 24 h of
      recovery after receiving a CHO-enriched diet. Linear regression demonstrated a
      significant correlation between SR Ca release rate and muscle glycogen content (P
      < 0.01, r = 0.30). The 4 h of cycling exercise reduced Wpeak by 5.5%-8.9% at
      different cadences (P < 0.05), and Wpeak was normalized after 4 h of recovery
      with CHO, whereas Wpeak remained depressed (P < 0.05) after water provision.
      Wpeak was fully recovered after 24 h in both the H2O and the CHO group.
      CONCLUSION: In conclusion, the present results suggest that low muscle glycogen
      depresses muscle SR Ca release rate, which may contribute to fatigue and delayed
      recovery of Wpeak 4 h postexercise.

PMID- 24091993
TI  - Reduced risk of brain cancer mortality from walking and running.
AB  - PURPOSE: This study aimed to test prospectively whether exercise is associated
      with lower brain cancer mortality in 111,266 runners and 42,136 walkers from the
      National Runners' and Walkers' Health Studies. METHODS: Hazard ratios and 95%
      confidence intervals (95% CI) from Cox proportional hazards analyses of mortality
      versus metabolic equivalent hours per day of exercise (MET-hours per day, where 1
      MET = 3.5 mL O2.kg.min, or approximately 1-km run). RESULTS: The National Death
      Index identified 110 brain cancer deaths during an 11.7-yr average follow-up.
      Runners and walkers were combined because the brain cancer risk reduction did not
      differ significantly between MET-hours per day run and MET-hours per day walked
      (P = 0.66). When adjusted for sex, age, race, education, and cohort effects, the
      risk for brain cancer mortality was 43.2% lower for those who exercised 1.8 to
      3.5 MET.h.d (95% CI = 2.6%-66.8% lower, P = 0.04) and 39.8% lower for those who
      exercised >= 3.6 MET.h.d (95% CI = 0.0%-64.0% lower, P = 0.05) compared with <1.8
      MET.h.d at baseline. Pooling the runners and walkers who expended >= 1.8 MET.h.d
      showed a 42.5% lower risk of brain cancer mortality for the entire sample (95%
      CI: 8.0 to 64.1, P = 0.02) and 40.0% lower risk when three deaths that occurred
      within 1 yr of the baseline survey were excluded (95% CI = 1.3%-62.4%, P = 0.04).
      CONCLUSIONS: The risk for fatal brain cancer decreased in association with
      running and walking energy expenditure. Our ability to detect an exercise-brain
      cancer relationship may relate to the use of cohorts specifically designed to
      detect exercise-health associations, and the calculation of exercise energy
      expenditure from kilometers per day walked and run rather than time spent
      exercising.

PMID- 24091992
TI  - Dynamic interactions of gas exchange, body mass, and progressive exercise in
      children.
AB  - PURPOSE: Cardiopulmonary exercise testing (CPET) is increasingly used as a
      biomarker of fitness in children. Maximal or peak values remain the most common
      variables obtained in CPET, but these physiologically challenging high-intensity
      work rates (WR) are often not achieved. We hypothesized that interactions of gas
      exchange, heart rate (HR), and WR CPET variables (slopes) could yield useful
      mechanistic and clinical insights that might enhance the clinical utility of CPET
      in children. We further hypothesized that the dependence of the slope on body
      mass could be predicted by the first-principle analysis of body size and
      physiological response. METHODS: One hundred and sixty-nine healthy participants
      (8-18 yr old, body mass index <95th percentile, 82 females) underwent dual x-ray
      absorptiometry scan to estimate lean body mass (LBM) and performed a ramp-type
      progressive cycle ergometry exercise protocol with a breath-by-breath measurement
      of gas exchange. Linear regression was used to calculate the slopes among VO2,
      VCO2, VE, HR, and WR. RESULTS: DeltaWR/DeltaHR (r = 0.87) and DeltaVO2/DeltaHR (r
      = 0.96) were strongly correlated with VO2peak, whereas DeltaVO2/DeltaWR (r =
      0.42) and DeltaVE/DeltaVCO2 (r = -0.51) were mildly correlated with peak values.
      LBM was more highly correlated with those slopes predicted to be body size
      dependent (P < 0.0001) compared with total body mass. CONCLUSIONS: The data
      largely supported our original hypotheses. Unlike peak or maximal values, which
      are derived from no more than a few data points at the end of a progressive
      exercise test, the CPET slopes were calculated from a much larger data set
      obtained throughout the test. An analysis of these slopes might ultimately prove
      useful clinically and in research studies when peak values are not achieved.

PMID- 24091994
TI  - Paraspinal muscle morphology and composition: a 15-yr longitudinal magnetic
      resonance imaging study.
AB  - PURPOSE: The purposes of this study were to define the natural progression of age
      related changes of the lumbar paraspinal muscles during adulthood and to
      investigate the influence of lifestyle and individual factors (e.g., physical
      activity levels at work and leisure, body mass index, and low back pain [LBP]).
      METHODS: This population-based longitudinal study included a sample of 99 adult
      male twins. Data were collected through a structured interview, physical
      examination, and magnetic resonance imaging. Measurements of the lumbar
      multifidus and erector spinae muscles were obtained from T2-weighted axial images
      at L3-L4 and L5-S1 at baseline and 15-yr follow-up. Muscle cross-sectional area
      (CSA), functional CSA (FCSA) (fat-free mass), and FCSA/CSA (composition) as well
      as CSA and FCSA asymmetry and FCSA/CSA side-to-side differences were measured.
      RESULTS: Subjects' mean +/- SD age was 47.3 +/- 7.4 yr at baseline and 62.3 +/-
      8.0 yr at follow-up. During the 15-yr period, both muscles exhibited a decrease
      in CSA and FCSA and an increase in fatty infiltration and side-to-side
      differences in size and composition at both spinal levels. Both muscles displayed
      greater changes at L5-S1 than L3-L4. Age and BMI were found to be significantly
      associated with the degree of paraspinal muscle changes over time. However, there
      was no association between the change in paraspinal muscle size, composition, or
      asymmetry with the level of physical demands at work or leisure or LBP history.
      CONCLUSIONS: The present longitudinal study suggests that over adulthood, the
      multifidus and erector spinae undergo similar morphological changes. Moreover,
      our findings suggest that the long-term progression of lumbar paraspinal muscle
      changes evaluated through magnetic resonance imaging are not associated with the
      range of physical demand levels as were typical of Finnish men or LBP history.

PMID- 24091995
TI  - Evidence of disturbed sleep and increased illness in overreached endurance
      athletes.
AB  - PURPOSE: This study aimed to examine whether (i) objective markers of sleep
      quantity and quality are altered in endurance athletes experiencing overreaching
      in response to an overload training program and (ii) potential reduced sleep
      quality would be accompanied with a higher prevalence of upper respiratory tract
      infections in this population. METHODS: Twenty-seven trained male triathletes
      were randomly assigned to either overload (n = 18) or normal (CTL, n = 9)
      training groups. Respective training programs included a 1-wk moderate training
      phase followed by a 3-wk period of overload or normal training, respectively, and
      then a subsequent 2-wk taper. Maximal aerobic power and oxygen uptake (VO2max)
      from incremental cycle ergometry were measured after each phase, whereas mood
      states and incidences of illness were determined from questionnaires. Sleep was
      monitored every night of the 6 wk using wristwatch actigraphy. RESULTS: Of the 18
      overload training group subjects, 9 were diagnosed as functionally overreached (F
      OR) after the overload period, as based on declines in performance and VO2max
      with concomitant high perceived fatigue (P < 0.05), whereas the other 9 overload
      subjects showed no decline in performance (AF, P > 0.05). There was a significant
      time-group interaction for sleep duration (SD), sleep efficiency (SE), and
      immobile time (IT). Only the F-OR group demonstrated a decrease in these three
      parameters (-7.9% +/- 6.7%, -1.6% +/- 0.7%, and -7.6% +/- 6.6% for SD, SE, and
      IT, respectively, P < 0.05), which was reversed during the subsequent taper
      phase. Higher prevalence of upper respiratory tract infections were also reported
      in F-OR (67%, 22%, and 11% incidence rate for F-OR, AF, and CTL, respectively).
      CONCLUSION: This study confirms sleep disturbances and increased illness in
      endurance athletes who present with symptoms of F-OR during periods of high
      volume training.

PMID- 24091996
TI  - 8-Hydroxy-efavirenz, the primary metabolite of the antiretroviral drug Efavirenz,
      stimulates the glycolytic flux in cultured rat astrocytes.
AB  - In active antiretroviral therapy antiretroviral drugs are employed for the
      restoration of a functional immune system in patients suffering from the acquired
      immunodeficiency syndrome. However, potential adverse effects of such compounds
      to brain cells are discussed in connection with the development of neurocognitive
      impairments in patients. To investigate potential effects of antiretroviral drugs
      on cell viability and the glycolytic flux of brain cells, astrocyte-rich primary
      cultures were exposed to various antiretroviral compounds, including the non
      nucleoside reverse transcriptase inhibitor efavirenz. In a concentration of 10
      MUM, neither efavirenz nor any of the other investigated antiretroviral compounds
      acutely compromised the cell viability nor altered glucose consumption or lactate
      production. In contrast, the primary metabolite of efavirenz, 8-hydroxy
      efavirenz, stimulated the glycolytic flux in viable astrocytes in a time- and
      concentration-dependent manner with half-maximal and maximal effects at
      concentrations of 5 and 10 MUM, respectively. The stimulation of glycolytic flux
      by 8-hydroxy-efavirenz was not additive to that obtained for astrocytes that were
      treated with the respiratory chain inhibitor rotenone and was abolished by
      removal of extracellular 8-hydroxy-efavirenz. In a concentration of 10 MUM, 8
      hydroxy-efavirenz and efavirenz did not affect mitochondrial respiration, while
      both compounds lowered in a concentration of 60 MUM significantly the oxygen
      consumption by mitochondria that had been isolated form cultured astrocytes,
      suggesting that the stimulation of glycolytic flux by 8-hydroxy-efavrienz is not
      caused by direct inhibition of respiration. The observed alteration of astrocytic
      glucose metabolism by 8-hydroxy-efavirenz could contribute to the adverse
      neurological side effects reported for patients that are chronically treated with
      efavirenz-containing medications. 

PMID- 24091997
TI  - Vindicating virtue: a critical analysis of the situationist challenge against
      Aristotelian moral psychology.
AB  - This article provides a critical analysis of the situationist challenge against
      Aristotelian moral psychology. It first outlines the details and results from
      four paradigmatic studies in psychology that situationists have heavily drawn
      upon in their critique of the Aristotelian conception of virtuous
      characteristics, including studies conducted by Hartshorne and May (1928), Darley
      and Batson (Journal of Personality and Social Psychology 27:100-108, 1973), Isen
      and Levin (Journal of Personality and Social Psychology 21:384-388, 1972), and
      Milgram (Journal of Abnormal and Social Psychology 67:371-378, 1963). It then
      presents ten problems with the way situationists have used these studies to
      challenge Aristotelian moral psychology. After challenging the situationists on
      these grounds, the article then proceeds to challenge the situationist
      presentation of the Aristotelian conception, showing that situationists have
      provided an oversimplified caricature of it that goes against the grain of much
      Aristotelian text. In evaluating the situationist challenge against the actual
      results from empirical research as well as primary Aristotelian text, it will be
      shown that the situationist debate has advanced both an extreme, untenable view
      about the nature of characteristics and situations, as well as an inaccurate
      presentation of the Aristotelian view. 

PMID- 24091998
TI  - 2,9-Dicarbonyl-1,10-phenanthroline derivatives with an unprecedented
      Am(III)/Eu(III) selectivity under highly acidic conditions.
AB  - Four lipophilic 1,10-phenanthroline di(thio)amide, diester or diketone
      derivatives were studied as ligands for Am(III)/Eu(III) separation from acidic
      media. The synthesis of these compounds is reported together with the extraction
      tests in different solvents (kerosene, octanol and o-nitrophenyl hexyl ether),
      HNO3 concentrations and ratios between the ligand and the synergistic agent (Br
      Cosan). The promising results obtained from the large number of solvent
      extraction tests carried out show that it might be possible to apply this class
      of ligands to advanced reprocessing of spent nuclear fuel. The experimental data
      indicate that, under the conditions that simulate the real radioactive waste, the
      extraction efficiency and Am/Eu separation factors are particularly high, thus
      suggesting that the combination of soft heterocyclic N-donor atoms and hard
      carbonyl groups of ester and amides affords a tetradentate donor set of atoms
      (ONNO) that gives rise to remarkable selectivities. ESI-MS studies and DFT
      calculations shed light on the possible structure of the Eu(3+) complexes
      indicating that the 1 : 1 : 2 (cation : ligand : anion) complex is slightly more
      stable than the 1 : 2 : 1 species.

PMID- 24091999
TI  - The reaction of formaldehyde carbonyl oxide with the methyl peroxy radical and
      its relevance in the chemistry of the atmosphere.
AB  - The reaction of formaldehyde carbonyl oxide (H2COO) with the methyl peroxy
      radical (CH3OO), a prototype of the reactions of carbonyl oxides with alkyl
      peroxy radicals of potential interest in atmospheric chemistry, has been
      investigated by means of quantum-mechanical electronic structure methods (CASSCF,
      CASPT2, UQCISD, and UCCSD(T)) and DFT functionals (B3LYP, BH&HLYP, M05 and M06
      2X). Two reaction paths have been found for the lowest-barrier reaction, namely
      the CH3OO radical addition to the carbon atom of H2COO leading to the formation
      of the CH3OOCH2OO radical adduct. Both pathways begin with the formation of a pre
      reactive complex with binding energies of 5.39 and 5.13 kcal mol(-1). The
      corresponding transition states are predicted to lie 2.64 and 0.25 kcal mol(-1),
      respectively, below the energy of the reactants and the rate constant of the
      global reaction is calculated to be 3.74 * 10(-12) cm(3) molecules(-1) s(-1) at
      298 K. Since the CH3OOCH2OO radical adduct is formed with an internal energy
      excess of about 45 kcal mol(-1), it can decompose unimolecularly into
      formaldehyde and the CH2(O)OOCH radical. This unimolecular decomposition involves
      an intramolecular H-atom transfer followed by the decomposition of the
      CH2OOCH2OOH radical intermediate. Kinetic calculations based on the collision
      reaction master equation employing the MultiWell Program Suite reveal that the
      CH3OOCH2OO radical adduct is stabilized in 86.9%, whereas 13.10% of the reaction
      corresponds to the formation of H2CO plus the CH2(O)OOH radical. It is concluded
      that the methyl peroxy radical addition to substituted carbonyl oxides might be
      the source of low volatility oligomers observed in secondary organic aerosols in
      chamber studies. 

PMID- 24092000
TI  - Effect of co-transporter blockers on non-synaptic epileptiform activity
      computational simulation.
AB  - The important role of cation-chloride co-transporters in epilepsy is being
      supported by an increasing number of investigations. However, enormous complexity
      is involved since the action of these co-transporters has effects on the ionic
      homeostasis influencing directly the neuronal excitability and the tissue
      propensity to sustain seizure. To unravel the complex mechanisms involving the co
      transporters action during seizure, this paper shows simulations of non-synaptic
      epileptiform activity and the effect of the blockage of the two different types
      of cation-chloride co-transporters present in the brain: Na, K and 2Cl co
      transporter (NKCC) and K and Cl co-transporter (KCC). The simulations were
      performed with an electrochemical model representing the non-synaptic structure
      of the granule cell layer of the dentate gyrus (DG) of the rat hippocampus. The
      simulations suggest: (i) the potassium clearance is based on the systemic
      interplay between the Na/K pump and the NKCC co-transporters; (ii) the
      simultaneous blockage of the NKCC of the neurons and KCC of glial cells acts
      efficiently suppressing the epileptiform activities; and (iii) the simulations
      show that depending on the combined blockage of the co-transporters, the
      epileptiform activities may be suppressed or enhanced. 

PMID- 24092001
TI  - The response of Paracoccus sp. SKG to acetonitrile-induced oxidative stress.
AB  - Organic solvents enhance intracellular oxidative stress and induce various
      physiological responses in bacteria. The study shows the morphological changes in
      Paracoccus sp. SKG when exposed to higher concentrations of acetonitrile, which
      alter the composition of the membrane fatty acid that accompanies the increase in
      K(+) efflux. This enhances the oxidative stress with greater activities of
      catalase and super oxide dismutase (SOD). The increased oxidative stress results
      in the generation of free radicals, which was confirmed by electron paramagnetic
      resonance (EPR) studies. The free radical scavenging activities were measured by
      ABTS and DPPH to understand the non-enzymatic defensive system during oxidative
      stress. The studies demonstrate the increase in free radicals in association with
      enzymatic and non-enzymatic defense systems under solvent stress. 

PMID- 24092002
TI  - Iron(II) spin crossover films on Au(111): scanning probe microscopy and
      photoelectron spectroscopy.
AB  - The growth of films of [H2B(pz)2]Fe(ii)(bpy) on Au(111) is characterized from the
      bilayer film to multilayer film regime. Scanning tunneling microscopy shows a
      transition from a well-ordered, uniform bilayer film to a poorly-ordered film at
      larger thicknesses. Previous local tunneling spectroscopy and conductance mapping
      in bilayer films permit the identification of coexisting molecular spin-states at
      all temperatures. New ultraviolet photoelectron spectroscopy is consistent with
      this picture and in agreement with the density of states calculated by density
      functional theory. In thicker films with a polycrystalline morphology, evidence
      for a more bulk-like change in spin composition as a function of temperature is
      obtained by observing the reduction in intensity of Fe 2p core level satellites
      in X-ray photoelectron spectra. 

PMID- 24092003
TI  - Effects of actinobacteria on plant disease suppression and growth promotion.
AB  - Biological control and plant growth promotion by plant beneficial microbes has
      been viewed as an alternative to the use of chemical pesticides and fertilizers.
      Bacteria and fungi that are naturally associated with plants and have a
      beneficial effect on plant growth by the alleviation of biotic and abiotic
      stresses were isolated and developed into biocontrol (BCA) and plant growth
      promoting agents (PGPA). Actinobacteria are a group of important plant-associated
      spore-forming bacteria, which have been studied for their biocontrol, plant
      growth promotion, and interaction with plants. This review summarizes the effects
      of actinobacteria as BCA, PGPA, and its beneficial associations with plants. 

PMID- 24092005
TI  - Metabolism of L-methionine linked to the biosynthesis of volatile organic sulfur
      containing compounds during the submerged fermentation of Tuber melanosporum.
AB  - Tuber melanosporum, known as the black diamond of cuisine, is highly appreciated
      for its unique and characteristic aroma, which is mainly due to its volatile
      organic sulfur-containing compounds (VOSCs). In this work, by adding 5 g/L L
      methionine to the fermentation medium, the activities of aminotransferase and
      alpha-ketoacid decarboxylase were significantly enhanced by 103 and 250%,
      respectively, while the activities of alcohol dehydrogenase and demethiolase were
      decreased by 277 and 39%. Then, the six VOSCs, i.e., methanethiol (MTL), dimethyl
      sulfide (DMS), dimethyl disulfide (DMDS), dimethyl trisulfide (DMTS), 3
      (methylthio)propanal (methional), and 3-(methylthio)-1-propanol (methionol), were
      first detected in the submerged fermentation of T. melanosporum. These results
      indicated that the biosynthesis of VOSCs was triggered by aminotransferase and
      alpha-ketoacid decarboxylase. The production of methional and methionol increased
      with the increased concentrations of L-methionine (i.e., 5, 10, 15, and 20 g/L)
      before day 4 of the culture protocol, and methionol was the major product in the
      Ehrlich pathway. The production of MTL was significantly decreased after day 4
      with a significantly increased DMDS, and DMDS was the major product of the
      demethiolation pathway. Compared with the demethiolation pathway with a total
      flux of sulfur of 11.33-24.32 MUM, the Ehrlich pathway with a total flux of
      sulfur of 6,149-10,330 MUM was considered the major pathway for the biosynthesis
      of VOSCs. This is the first report linking the metabolism of L-methionine to the
      biosynthesis of VOSCs by the Ehrlich and demethiolation pathways during the
      submerged fermentation of T. melanosporum.

PMID- 24092004
TI  - Community structure and abundance of ammonia-oxidizing archaea and bacteria after
      conversion from soybean to rice paddy in albic soils of Northeast China.
AB  - Community composition of ammonia-oxidizing archaea (AOA) and ammonia-oxidizing
      bacteria (AOB) in the albic soil grown with soybean and rice for different years
      was investigated by construction of clone libraries, denaturing gradient gel
      electrophoresis (DGGE), and quantitative polymerase chain reaction (q-PCR) by PCR
      amplification of the ammonia monooxygenase subunit A (amoA) gene. Soil samples
      were collected at two layers (0-5 and 20-25 cm) from a soybean field and four
      rice paddy fields with 1, 5, 9, and 17 years of continuous rice cultivation. Both
      the community structures and abundances of AOA and AOB showed detectable changes
      after conversion from soybean to rice paddy judged by clone library, DGGE, and q
      PCR analyses. In general, the archaeal amoA gene abundance increased after
      conversion to rice cultivation, while bacterial amoA gene abundance decreased.
      The abundances of both AOA and AOB were higher in the surface layer than the
      bottom one in the soybean field, but a reverse trend was observed for AOB in all
      paddy samples regardless of the duration of paddy cultivation. Phylogenetic
      analysis identified nine subclusters of AOA and seven subclusters of AOB.
      Community composition of both AOA and AOB was correlated with available ammonium
      and increased pH value caused by flooding in multiple variance analysis.
      Community shift of AOB was also observed in different paddy fields, but the two
      layers did not show any detectable changes in DGGE analysis. Conversion from
      soybean to rice cultivation changed the community structure and abundance of AOA
      and AOB in albic agricultural soil, which requires that necessary cultivation
      practice be followed to manage the N utilization more effectively.

PMID- 24092006
TI  - Odorant binding proteins: a biotechnological tool for odour control.
AB  - The application of an odorant binding protein for odour control and fragrance
      delayed release from a textile surface was first explored in this work. Pig OBP-1
      gene was cloned and expressed in Escherichia coli, and the purified protein was
      biochemically characterized. The IC50 values (concentrations of competitor that
      caused a decay of fluorescence to half-maximal intensity) were determined for
      four distinct fragrances, namely, citronellol, benzyl benzoate, citronellyl
      valerate and ethyl valerate. The results showed a strong binding of citronellyl
      valerate, citronellol and benzyl benzoate to the recombinant protein, while ethyl
      valerate displayed weaker binding. Cationized cotton substrates were coated with
      porcine odorant binding protein and tested for their capacity to retain
      citronellol and to mask the smell of cigarette smoke. The immobilized protein
      delayed the release of citronellol when compared to the untreated cotton.
      According to a blind evaluation of 30 assessors, the smell of cigarette smoke,
      trapped onto the fabrics' surface, was successfully attenuated by porcine odorant
      binding protein (more than 60 % identified the weakest smell intensity after
      protein exposure compared to beta-cyclodextrin-treated and untreated cotton
      fabrics). This work demonstrated that porcine odorant binding protein can be an
      efficient solution to prevent and/or remove unpleasant odours trapped on the
      large surface of textiles. Its intrinsic properties make odorant binding proteins
      excellent candidates for controlled release systems which constitute a new
      application for this class of proteins.

PMID- 24092007
TI  - Recovery of microbial diversity and activity during bioremediation following
      chemical oxidation of diesel contaminated soils.
AB  - To improve the coupling of in situ chemical oxidation and in situ bioremediation,
      a systematic analysis was performed of the effect of chemical oxidation with
      Fenton's reagent, modified Fenton's reagent, permanganate, or persulfate, on
      microbial diversity and activity during 8 weeks of incubation in two diesel
      contaminated soils (peat and fill). Chemical oxidant and soil type affected the
      microbial community diversity and biodegradation activity; however, this was only
      observed following treatment with Fenton's reagent and modified Fenton's reagent,
      and in the biotic control without oxidation. Differences in the highest overall
      removal efficiencies of 69 % for peat (biotic control) and 59 % for fill
      (Fenton's reagent) were partially explained by changes in contaminant soil
      properties upon oxidation. Molecular analysis of 16S rRNA and alkane
      monooxygenase (alkB) gene abundances indicated that oxidation with Fenton's
      reagent and modified Fenton's reagent negatively affected microbial abundance.
      However, regeneration occurred, and final relative alkB abundances were 1-2
      orders of magnitude higher in chemically treated microcosms than in the biotic
      control. 16S rRNA gene fragment fingerprinting with DGGE and prominent band
      sequencing illuminated microbial community composition and diversity differences
      between treatments and identified a variety of phylotypes within Alpha-, Beta-,
      and Gammaproteobacteria. Understanding microbial community dynamics during
      coupled chemical oxidation and bioremediation is integral to improved biphasic
      field application.

PMID- 24092008
TI  - Highly enantioselective oxidation of phenyl methyl sulfide and its derivatives
      into optically pure (S)-sulfoxides with Rhodococcus sp. CCZU10-1 in an n-octane
      water biphasic system.
AB  - Enantiopure sulfoxides can be prepared via the asymmetric oxidation of sulfides
      using sulfide monooxygenases. The n-octane-water biphasic system was chosen for
      the bio-oxidation of a water-insoluble phenyl methyl sulfide (PMS) by Rhodococcus
      sp. CCZU10-1. In this n-octane-water system, the optimum reaction conditions were
      obtained. (S)-phenyl methyl sulfoxide ((S)-PMSO) with >99.9 % enantiomeric excess
      formed at 55.3 mM in the n-octane-water biphasic system. Using fed-batch method,
      a total of 118 mM (S)-PMSO accumulated in 1-L reaction mixture after the 7th
      feed, and no (R)-PMSO and sulfone were detected. Moreover, Rhodococcus sp. CCZU10
      1 displayed fairly good activity and enantioselectivity toward other sulfides. In
      conclusion, Rhodococcus sp. CCZU10-1 is a promising biocatalyst for synthesizing
      highly optically active sulfoxides.

PMID- 24092009
TI  - Nisin-activated hydrophobic and hydrophilic surfaces: assessment of peptide
      adsorption and antibacterial activity against some food pathogens.
AB  - An effective antimicrobial packaging or food contact surface should be able to
      kill or inhibit micro-organisms that cause food-borne illnesses. Setting up such
      systems, by nisin adsorption on hydrophilic and hydrophobic surfaces, is still a
      matter of debate. For this purpose, nisin was adsorbed on two types of low
      density polyethylene: the hydrophobic native film and the hydrophilic acrylic
      acid-treated surface. The antibacterial activity was compared for those two films
      and it was highly dependent on the nature of the surface and the nisin-adsorbed
      amount. The hydrophilic surfaces presented higher antibacterial activity and
      higher amount of nisin than the hydrophobic surfaces. The effectiveness of the
      activated surfaces was assessed against Listeria innocua and the food pathogens
      Listeria monocytogenes, Bacillus cereus, and Staphylococcus aureus. S. aureus was
      more sensitive than the three other test bacteria toward both nisin
      functionalized films. Simulation tests to mimic refrigerated temperature showed
      that the films were effective at 20 and 4  degrees C with no significant
      difference between the two temperatures after 30 min of exposure to culture
      media.

PMID- 24092010
TI  - A developmental stage of hyphal cells shows riboflavin overproduction instead of
      sporulation in Ashbya gossypii.
AB  - The hemiascomycete Ashbya gossypii develops a mycelium. Nutritional stress leads
      to its differentiation into sporangia. These generate spores. In parallel, the
      yellow pigment riboflavin is produced. Intracellularly accumulated riboflavin,
      made visible as a bright green fluorescence, was observed in only 60% of the
      hyphal cells. For the remaining 40%, it was unclear whether these cells simply
      export riboflavin or its biosynthesis remains down-regulated in contrast to the
      accumulating cells. The approach followed in this work was to convert the hyphae
      into protoplasts by enzymatic degradation of the cell wall. Afterwards, the
      protoplasts were sorted by fluorescence-activated cell sorting on the basis of
      riboflavin accumulation. When a reporter strain expressing lacZ under the control
      of the most important riboflavin biosynthesis promoter, RIB3, was used, green
      protoplasts were found to have more than tenfold greater reporter activity than
      hyaline protoplasts. This was true on the basis of total protein as well as on
      the basis of hexokinase specific activity, a marker for constitutive expression.
      These results allow the conclusion that hyphal cells of A. gossypii differ in
      phenotype regarding riboflavin overproduction and accumulation.

PMID- 24092011
TI  - Effects of olive mill wastewater on soil carbon and nitrogen cycling.
AB  - This study investigated the cycling of C and N following application of olive
      mill wastewater (OMW) at various rates (0, 42, 84, and 168 m(3)/ha). OMW
      stimulated respiration rate throughout the study period, but an increase in soil
      organic matter was observed only at the highest rate. Soil phenol content
      decreased rapidly within 2 weeks following application but neither phenol oxidase
      and peroxidase activity nor laccase gene copies could explain this response. Soil
      NH4 (+)-N content increased in response to OMW application rate, while an
      opposite trend observed for NO3 (-)-N, which attributed to immobilization. This
      decrease was in accordance with amoA gene copies of archaeal and bacterial
      ammonia oxidizers in the first days following OMW application. Afterwards,
      although amoA gene copies and potential nitrification rates recovered to values
      similar to or higher than those in the non-treated soils, NO3 (-)-N content did
      not change among the treatments. A corresponding increase in denitrifying gene
      copies (nirK, nirS, nosZ) during that period indicates that denitrification,
      stimulated by OMW application rate, was responsible for this effect; a hypothesis
      consistent with the decrease in total Kjeldahl nitrogen content late in the
      season. The findings suggest that land application of OMW is a promising practice
      for OMW management, even at rates approaching the soil water holding capacity.

PMID- 24092012
TI  - Biosafety and colonization of Burkholderia multivorans WS-FJ9 and its growth
      promoting effects on poplars.
AB  - Burkholderia cepacia complex (Bcc) is a group of bacteria with conflicting
      biological characteristics, which make them simultaneously beneficial and harmful
      to humans. They have been exploited for biocontrol, bioremediation, and plant
      growth promotion. However, their capacity as opportunistic bacteria that infect
      humans restricts their biotechnological applications. Therefore, the risks of
      using these bacteria should be assessed. In this study, Burkholderia multivorans
      WS-FJ9 originally isolated from pine rhizosphere, which was shown to be efficient
      in solubilizing phosphate, was evaluated with respect to its biosafety,
      colonization in poplar rhizosphere, and growth-promoting effects on poplar
      seedlings. Pathogenicity of B. multivorans WS-FJ9 on plants was determined
      experimentally using onion and tobacco as model plants. Onion bulb inoculated
      with B. multivorans WS-FJ9 showed slight hypersensitive responses around the
      inoculation points, but effects were not detectable based on the inner color and
      odor of the onion. Tobacco leaves inoculated with B. multivorans WS-FJ9 exhibited
      slightly water-soaked spots around the inoculation points, which did not expand
      or develop into lesions even with repeated incubation. Pathogenicity of the
      strain in alfalfa, which has been suggested as an alternative Bcc model for mice,
      was not detectable. Results from gene-specific polymerase chain reactions showed
      that the tested B. multivorans WS-FJ9 strain did not possess the BCESM and cblA
      virulence genes. Scanning electron microscopy revealed that the colonization of
      the WS-FJ9 strain reached 1.4 * 10(4) colony forming units (cfu) g(-1)
      rhizosphere soil on day 77 post-inoculation. The B. multivorans WS-FJ9 strain
      could colonize the rhizosphere as well as the root tissues and cells of poplars.
      Greenhouse evaluations in both sterilized and non-sterilized soils indicated that
      B. multivorans WS-FJ9 significantly promoted growth in height, root collar
      diameter, and plant biomass of inoculated poplar seedlings compared with
      controls. Phosphorus contents of roots and stems of treated seedlings were 0.57
      and 0.55 mg g(-1) higher than those of the controls, respectively. Phosphorus
      content was lower in the rhizosphere soils by an average of 1.03 mg g(-1)
      compared with controls. The results demonstrated that B. multivorans WS-FJ9 is a
      nonpathogenic strain that could colonize the roots and significantly promote the
      growth of poplar seedlings.

PMID- 24092014
TI  - In-situ photoelectron microspectroscopy and imaging of electrochemical processes
      at the electrodes of a self-driven cell.
AB  - The challenges in development of solid oxide fuel cells (SOFCs) are reducing
      their dimensions and increasing their efficiency and durability, which requires
      physicochemical characterization at micro-scales of the device components during
      operation conditions. Recently, the unique potential of scanning photoelectron
      microscopy (SPEM) has been demonstrated by in-situ studies of externally-driven
      SOFCs, which mimic real devices. Here we overcome the gap between model and real
      systems using a single-chamber Ni|YSZ|Mn SOFC, supporting a range of self-driven
      electrochemical reactions in variable gas environments and temperatures. The
      reported SPEM results, obtained during spontaneous electrochemical processes
      occurring in reactive gas ambient, demonstrate the chemical evolution of
      electrodic material, in particular the lateral distribution of the oxidation
      state and the induced local potential, clearly marking out the electrochemically
      most active micro-regions of the Ni anode.

PMID- 24092015
TI  - Single primary fetal lung cells generate alveolar structures in vitro.
AB  - Organ morphogenesis, including lung morphogenesis, involves a series of cellular
      behaviors that are difficult to observe and document in vivo due to current
      limitations in imaging techniques. Therefore, in vitro models are necessary to
      study these cellular behaviors as well as basic developmental processes relevant
      to in vivo morphogenesis. Here, we describe a novel in vitro three-dimensional
      (3D) culture system for assessing mouse lung alveolar morphogenesis using primary
      fetal mouse lung cells cultured in Matrigel supplemented with fibroblast growth
      factor 10 and hepatocyte growth factor. In our in vitro 3D culture system, single
      primary mouse fetal lung cells successfully grew, developed lumen, and formed
      multivesicular epithelial structures, resulting in a morphology that was highly
      similar to that of lung alveoli. This culture system is a useful tool for
      investigating the cellular and molecular mechanisms involved in lung alveolar
      morphogenesis.

PMID- 24092016
TI  - Trim14 overexpression causes the same transcriptional changes in mouse embryonic
      stem cells and human HEK293 cells.
AB  - The trim14 (pub, KIAA0129) gene encodes the TRIM14 protein which is a member of
      the tripartite motif (TRIM) family. Previously, we revealed high expression
      levels of trim14 in HIV- or SIV-associated lymphomas and demonstrated the
      influence of trim14 on mesodermal differentiation of mouse embryonic stem cells
      (mESC). In the present work, to elucidate the role of trim14 in normal and
      pathological processes in the cell, we used two different types of cells
      transfected with trim14: mESC and human HEK293. Using subtractive hybridization
      and real-time PCR, we found a number of genes which expression was elevated in
      trim14-transfected mESC: hsp90ab1, prr13, pu.1, tnfrsf13c (baff-r), tnfrsf13b
      (taci), hlx1, hbp1, junb, and pdgfrb. A further analysis of the trim14
      transfected mESC at the initial stage of differentiation (embryoid bodies (EB)
      formation) showed essential changes in the expression of these upregulated genes.
      The transfection of trim14 into HEK293 also induced an enhanced expression of the
      several genes upregulated in trim14-transfected mESC (hsp90ab1, prr13, pu.1,
      tnfrsf13c (baff-r), tnfrsf13b (taci), and hlx1). Summarizing, we found similar
      genes that participated in trim14-directed processes both in mESC and in HEK293.
      These results demonstrate the presence of the similar mechanism of trim14 gene
      action in different types of mammalian cells.

PMID- 24092017
TI  - Nuclear factor Y (NF-Y) regulates the proximal promoter activity of the mouse
      collagen alpha1(XI) gene (Col11a1) in chondrocytes.
AB  - Type XI collagen, a heterotrimer composed of alpha1(XI), alpha2(XI), and
      alpha3(XI), plays a critical role in cartilage formation and in skeletal
      morphogenesis. However, the transcriptional regulation of alpha1(XI) collagen
      gene (Col11a1) in chondrocyte is poorly characterized. In this study, we
      investigated the proximal promoter of mouse Col11a1 gene in chondrocytes. Major
      transcription start site was located at -299 bp upstream of the translation start
      site, and the proximal promoter lacks a TATA sequence but has a high guanine
      cytosine (GC) content. Cell transfection experiments demonstrated that the
      segment from -116 to -256 is necessary for activation of the proximal Col11a1
      promoter, and an electrophoretic mobility shift assay showed that a nuclear
      protein is bound to the segment from -116 to -176 in this promoter. Additional
      comparative and in silico analyses demonstrated that an ATTGG sequence, which is
      critical for binding to nuclear factor Y (NF-Y), is within the highly conserved
      region from -135 to -145. Interference assays using wild-type and mutant
      oligonucleotide or with specific antibody revealed that NF-Y protein is bound to
      this region. Cell transfection experiments with reporter constructs in the
      absence of NF-Y binding sequence exhibited the suppression of the promoter
      activity. Furthermore, chromatin immunoprecipitation assay demonstrated that NF-Y
      protein is directly bound to this region in vivo, and overexpression of dominant
      negative NF-Y A mutant also inhibited the proximal promoter activity. Taken
      together, these results indicate that the transcription factor NF-Y regulates the
      proximal promoter activity of mouse Col11a1 gene in chondrocytes. 

PMID- 24092019
TI  - Ultrathin high-temperature oxidation-resistant coatings of hexagonal boron
      nitride.
AB  - Hexagonal boron nitride is a two-dimensional layered material that can be stable
      at 1,500  degrees C in air and will not react with most chemicals. Here we
      demonstrate large-scale, ultrathin, oxidation-resistant coatings of high-quality
      hexagonal boron nitride layers with controlled thicknesses from double layers to
      bulk. We show that such ultrathin hexagonal boron nitride films are impervious to
      oxygen diffusion even at high temperatures and can serve as high-performance
      oxidation-resistant coatings for nickel up to 1,100  degrees C in oxidizing
      atmospheres. Furthermore, graphene layers coated with a few hexagonal boron
      nitride layers are also protected at similarly high temperatures. These hexagonal
      boron nitride atomic layer coatings, which can be synthesized via scalable
      chemical vapour deposition method down to only two layers, could be the thinnest
      coating ever shown to withstand such extreme environments and find applications
      as chemically stable high-temperature coatings.

PMID- 24092018
TI  - Quantum dots induce heat shock-related cytotoxicity at intracellular environment.
AB  - Quantum dots (QDs) are semiconductor nanocrystals with unique optical properties.
      Different proteins or polymers are commonly bound to their surfaces to improve
      biocompatibility. However, such surface modifications may not provide sufficient
      protection from cytotoxicity due to photodegradation and oxidative degradation.
      In this study, the cytotoxic effects of QDs, CdTe, and CdSe/ZnS were investigated
      using cadmium-resistant cells. CdTe QDs significantly reduced cell viability,
      whereas, CdSe/ZnS treatment did not markedly decrease the cell number. CdTe QDs
      were cytotoxic in cadmium-resistant cells suggesting that internalized QDs
      degraded and cadmium ions contributed to the cytotoxic effects. CdTe QDs were
      consistently more cytotoxic than CdSe/ZnS QDs, but both QDs as well as cadmium
      ions activated heat shock protein 70B' promoter. QDs themselves are likely to
      contribute to HSP70B' promoter activation in cadmium-resistant cells, because
      CdSe/ZnS QDs do not release sufficient cadmium to activate this promoter. 

PMID- 24092021
TI  - Better medicine or more medicine, where are we heading?

PMID- 24092022
TI  - "Safe" oxygen saturation levels in extremely preterm infants: have we found a
      definite answer?

PMID- 24092023
TI  - Adaptive designs in clinical research.

PMID- 24092024
TI  - Assessment of pertussis vaccination strategies using a mathematical model of
      disease transmission.
AB  - Pertussis or whooping cough is a vaccine-preventable respiratory disease that has
      reemerged in the past decades. A higher morbidity and mortality has been recorded
      in infants, although cases have also been reported in adolescents and adults. The
      epidemiological scenario for this condition has urged to review and implement new
      strategies aimed at improving its control. However, many of these strategies have
      not been investigated in depth so as to be established as universal. In this
      context, mathematical models of disease transmission are useful decision-making
      tools. Using a mathematical model of pertussis, this study assessed the possible
      impact of the different control measures on the most vulnerable population (0-1
      year old infants). In particular, the analysis focused on the impact of including
      a booster vaccination at 11 years old, the effect of improving the coverage
      provided by primary doses, and the reduction of any delay in their
      administration. The assessment also estimated the effect of immunizing pregnant
      women. Results show that including a booster dose at 11 years reduces the
      incidence of pertussis by 3% in infants younger than 1 year old. In addition,
      administering primary doses in compliance with the schedule (with no delays)
      reduces pertussis incidence by 16%. Increasing coverage from 80% to 95% results
      in a signifcantly decreased incidence in the vulnerable population (38%). If the
      percentage of immunized pregnant women reaches 50%, the reduction of the most
      severe infant cases could be more than 43% (0-2 month-old infants). 

PMID- 24092025
TI  - Child psychomotor development and its relationship with socio-demographic and
      family stimulation factors in children from Bariloche, Argentina.
AB  - INTRODUCTION: This study analyzed the association between psychomotor development
      and socio-demographic and family stimulation factors in 3-year-old children from
      San Carlos de Bariloche. POPULATION AND METHODS: A total of 152 apparently
      healthy children aged 35-37 months old who attended municipal and private
      kindergartens were evaluated. Children's performance in personal-social, fne
      motor, language and gross motor skills development using the National Screening
      Test was analyzed. The relationship between environmental factors and the
      achievement of developmental milestones was studied using a multivariate logistic
      regression model. RESULTS: Twenty seven percent of children did not pass the
      test. The most common outcome measures associated with altered developmental
      milestones were no reading, low birth weight, and the parents' lower education
      level. The association with reading was always positive; and this also occurred
      in relation to the parents' education level. A low birth weight had a negative
      association with the possibility of passing four milestones, three of which were
      gross motor skills. Children who attended municipal kindergartens had a low
      performance in three language milestones, one personal-social milestone and one
      fne motor milestone when compared to national profles. CONCLUSIONS: The
      percentage of children who did not pass the test was 27%. The most common outcome
      measures associated with altered developmental milestones were lack of reading to
      the child, low birth weight, and the parents' lower education level.

PMID- 24092026
TI  - Impact of a quality improvement intervention on the incidence of unplanned
      extubations in a Pediatric Intensive Care Unit.
AB  - INTRODUCTION: An unplanned extubation (UEX) is a frequent and preventable adverse
      event of mechanical ventilation. OBJECTIVES: To fnd out the causes of unplanned
      extubation and assess the use of a quality improvement intervention to reduce
      this event rate. POPULATION: Patients with invasive mechanical ventilation for
      more than 12 hours over the period from May 1st 2010 and April 30th 2011 in a
      Pediatric Intensive Care Unit (PICU). DESIGN: Uncontrolled, before and after
      study. A quality improvement intervention was used over the period between
      November 2010 and April 2011, which included training PICU staff, establishing
      standards to fx the endotracheal tube and control its fxation. RESULTS: There
      were 395 patients admitted to the PICU, 262 (66%) were on mechanical ventilation
      for more than 12 hours. A total of 27 patients had 30 UEX events: 22 during the
      period between May and October 2010, and 8 during the period between November
      2010 and April 2011. The most common causes of UEX were incorrect fxation of the
      endotracheal tube (n= 11) and the use of a procedure of care (n= 11). Patients
      with UEX required additional days on mechanical ventilation: 7 (3-15.5) versus 5
      (2-8) days; p= 0.077 and hospitalization: 9.5 (5-19) versus 7 (4-10) days; p=
      0.049. During the implementation of the quality improvement intervention, the
      mean incidence of UEX decreased from 2.30 (95% CI: 1.12-3.49) to 0.86 (95% CI:
      0.27-1.44) per 100 days of mechanical ventilation (p= 0.037). CONCLUSIONS: The
      most common causes of UEX were the incorrect fxation of the endotracheal tube and
      the use of a procedure of care. The implementation of a quality improvement
      intervention reduced the incidence of UEX.

PMID- 24092027
TI  - Relationship between the level of physical activity and markers of cardiovascular
      health in Valencian adolescents (Spain).
AB  - INTRODUCTION: A sedentary lifestyle is not only a major cardiovascular risk
      factor from an early age, it also contributes to the development of other
      cardiovascular risk factors. The objective of this study was to determine the
      level of physical activity and relate it to cardiovascular risk markers in
      Valencian adolescents according to their anthropometric characteristics and
      gender. POPULATION AND METHODS: The following variables were assessed in a
      randomized sample of 583 Valencian adolescents (Spain) aged 12-18 years: level of
      physical activity, using a validated questionnaire; weight, height and waist
      circumference; aerobic capacity, using the multi-stage ftness test (Course
      Navette test); and muscle strength, using a manual dynamometry. RESULTS: In
      total, 57.60% of male adolescents and 14% of female adolescents complied with the
      recommendations for physical activity. The prevalence of excessive weight, waist
      circumference with risk, and aerobic capacity with risk was 24.90%, 29.30% and
      20.60%, respectively among boys, and 15.10%, 23.20% and 24.70% among girls (p
      <0.005). CONCLUSIONS: A higher level of physical activity in adolescents is
      related to a lower body mass index, a smaller waist circumference and less
      excessive weight in male adolescents, and to a higher aerobic capacity and a
      lower cardiovascular risk in both male and female adolescents. Aerobic capacity
      and waist circumference with risk are signifcantly higher among subjects with
      excessive weight.

PMID- 24092028
TI  - Referral and counter-referral system between secondary and tertiary care
      facilities in a children's hospital network of Greater Buenos Aires.
AB  - INTRODUCTION: Hospital El Cruce is a tertiary care facility which is part of a
      healthcare network that has been operating since July 2008 and includes health
      centers from five municipalities of the South of Greater Buenos Aires. The
      objective of the study was to describe the referral and counter-referral system
      at the pediatric intermediate medical care unit of the Hospital El Cruce, the
      tertiary level care of the network, and secondly to identify the critical points
      that could go against the consolidation of the network and to analyze the level
      of knowledge about it. POPULATION AND METHODS: This was a cross-sectional,
      prospective study conducted at the pediatric intermediate medical care unit of
      Hospital El Cruce between July 2008 and December 2010. Indicators related to
      patient admission and discharge were analyzed. A survey was administered to all
      the heads of the network's pediatric departments in order to assess the level of
      knowledge they had about it. RESULTS: A total of1677patients were hospitalized;
      83.9% were referred from the network. Of all referrals made, 71.1% were accepted.
      There were 156 patients (9.4%) who were counter-referred to the referring
      facility. The survey results showed that 70% of heads of pediatric departments
      were unaware of the range of services provided by the network. CONCLUSIONS:
      Health care exchange was predominantly based on accepting patients referred from
      secondary care facilities to Hospital El Cruce and a minimum number of counter
      referrals to referring facilities, with a radial pattern dynamics. There was
      scarce knowledge about the availability of the network health service delivery.

PMID- 24092029
TI  - Acute kidney injury in critically ill children: incidence and risk factors for
      mortality.
AB  - INTRODUCTION: Acute kidney injury is a common complication associated with an
      increase in mortality in children who require intensive care. The objective of
      this study was to determine the incidence of acute kidney injury and identify
      risk factors for mortality in critically ill patients hospitalized in our
      facility. PATIENTS AND METHODS: This was a prospective and observational study
      conducted at the Intensive Care Unit (ICU) of Hospital Pedro de Elizalde between
      2005 and 2009. All patients with acute kidney injury were included, and those
      with chronic renal failure, prerenal acute kidney injury, hepatorenal syndrome,
      newborn infants, and postoperative cardiovascular surgery patients were excluded.
      The sample was divided into survivors and deceased patients so as to identify
      risk factors for mortality using univariate and multivariate analyses, taking
      their clinical characteristics as predictive variable, and death at the ICU as
      the outcome variable. RESULTS: Out of 1496 patients, 66 developed acute kidney
      injury (4.4%). The cause was secondary in 72.8% of cases, and due to primary
      kidney disease in 27.2% of cases. Mortality rate was 44% (29 patients). The
      univariate analysis showed that the presence of anuria (p= 0.0003; OR: 7.01; 95%
      CI: 2.3-21.35) and the need of dialysis (p= 0.0009; OR: 6.35; 95% CI: 2.03-9.88)
      were signifcantly higher in deceased patients. The multiple regression analysis
      identifed that the need of dialysis (p = 0.0002; OR: 5.94; 95% CI: 1.85-19.04)
      was an independent risk factor for mortality. CONCLUSIONS: The incidence of acute
      kidney injury in critically ill children was 4.4%, and the need of dialysis was
      an independent predictor of mortality.

PMID- 24092030
TI  - Clinical findings in 32 patients with 22qll.2 microdeletion attended in the city
      of Cordoba, Argentina.
AB  - The 22q11.2 microdeletion is the most common deletion syndrome, with a prevalence
      of 1/4000-1/6000 among newborn infants and a wide phenotypic variability. The
      diagnosis of the 22q11.2 microdeletion is made through cytogenetics or
      fuorescence in situ hybridization (FISH). The objectives of this article were to
      describe the clinical features of 32 patients with 22q11.2 microdeletion and the
      fndings of other chromosomal abnormalities and genetic syndromes in
      phenotypically similar patients. This series was made up of 268 patients with
      clinical criteria supporting the diagnostic suspicion attended at the Hospital de
      Ninos and Hospital Privado, of Cordoba, between March 1st, 2004 and August 31st,
      2011. The following parameters were analyzed: age at the time of the diagnosis,
      sex, clinical manifestations, and mortality. Thirty-two patients (19 males and 13
      females) had a positive result for this deletion. The diagnosis was made mostly
      in their frst months and years of life (age range: 7 days old-31 years old). The
      clinical manifestations were: congenital heart diseases (22/32), thymic
      hypoplasia-agenesis/ recurrent infections (10/32), velopalatal insuffciency
      (8/32). Five patients died; four due to a complication associated with their
      cardiovascular disease and one due to multiple organ failure. The clinical
      manifestations of the syndrome were varied. 

PMID- 24092031
TI  - [Invasive mechanical ventilation: Update for the pediatrician].
AB  - In this review, we collect the fundamental concepts of the use of invasive
      mechanical ventilation (MV) in children, particularly in acute respiratory
      failure. MV is a common practice in the ICU and must be understood as a
      therapeutic intervention to replace the work of breathing while restores the
      balance between ventilatory demand and the patient's ability to sustain it. It is
      essential for the clinician to recognize that the goal of mechanical ventilatory
      support is not to normalize the patient's blood gases but providing a reasonable
      gas exchange; the benefts are obtained if the safety thresholds are not exceeded.
      Thus, this strategy has become the only tool available to limit the development
      of ventilator-induced lung injury (VILI). 

PMID- 24092032
TI  - [Pott puffy tumor: case report].
AB  - We present the case of a child with frontal sinusitis, who also suffers from a
      severe intracranial disease. Although sinusitis intracranial issues are rare
      nowadays, they include a wide range of serious entities such as meningitis, brain
      abscesses and thrombosis of the cavernous sinus. We emphasize the importance of
      early diagnosis and an adequate initial empirical treatment to prevent possible
      complications. Once they are presented, an aggressive surgical medical treatment
      is required for its resolution. 

PMID- 24092033
TI  - [Consensus in hospitalized newborn monitoring: part 2: monitoring according to
      levels of complexity].

PMID- 24092034
TI  - An unusual case of childhood sarcoidosis: an unusual clinical case.
AB  - Sarcoidosis is a systemic granulomatous disease of unknown etiology that may
      affect many systems, mainly lungs. Most of the patients present at stages I and
      II lung involvement. Pulmonary infltrates without hilar lymphadenopathy (state
      III) rarely occurs. Extrapulmonary organ involvement is common in pediatric
      sarcoidosis. The aim of this report is to present an unusual case of childhood
      sarcoidosis with stage III lung involvement without any extrapulmonary organ
      involvement. A 7-year-old girl presented with the complaints of malaise, fatigue,
      weight loss and dyspnea. There was patchy, bilateral ground glass view at high
      resolution computer tomography. Video assisted thoracoscopic lung biopsy was
      performed and histopathological examination showed nonnecrotising epitheloid-cell
      granulomas with giant cells. She did not have any hilar or extrapulmonary organ
      involvement and pulmonary sarcoidosis at stage III was diagnosed. Sarcoidosis
      should be considered in the differential diagnosis of children with interstitial
      lung disease. 

PMID- 24092035
TI  - [Multiorgan failure associated with hyperthermia in an infant with Prader-Willi
      syndrome. case report].
AB  - Heat stroke is a medical emergency characterized primarily by an elevated core
      temperature associated with a systemic inflammatory response, which causes
      multiple organ dysfunction in which encephalopathy predominates. If it is not
      early treated has high mortality. The Prader-Willi syndrome is a multisystem
      genetic disorder secondary to an abnormality in long arm chromosome 15 (15q11
      q13), characterized by neonatal central hypotonia, developmental delay,
      hypogonadism, hyperphagia and obesity. These patients are susceptible to
      developing thermoregulatory problems. We report the case of a 5-month-old infant,
      in whom a diagnosis of Prader-Willi syndrome was established in the course of a
      febrile episode without known focus, who developed multiorganic failure and
      rhabdomyolysis secondary to hyperthermia. 

PMID- 24092036
TI  - [Protein losing gastroenteropathy and possible relationship to cytomegalovirus
      infection: Menetrier disease in a child].
AB  - Menetrier's disease is a childhood protein-losing gastroenteropathy characterized
      by hypertrophy of the gastric mucosa, of unknown etiology, although most of
      reported cases have been associated with viral infections. Clinical manifestation
      is edema and biochemically there are hypoproteinemia and hypoalbuminemia. This
      disease is very rare in children and they have a benign and self-limiting course
      in contrast to adults where tend to be chronic and occasionally to become
      malignant. We present a child with Menetrier disease with edema and ascites
      possibly associated with a cytomegalovirus infection. 

PMID- 24092037
TI  - [Guidelines for home oxygen therapy management: Part 1: generality, indications
      and monitoring].

PMID- 24092038
TI  - [Human herpesvirus 8 related Kaposi's sarcoma in a pediatric liver transplant
      recipient: case report].
AB  - Patients under immunosuppressive treatment are at risk of developing malignant
      tumors. Primary infection or reactivation of human herpesvirus 8 (HHV-8) may
      predispose to Kaposi's sarcoma (KS) after solid organ transplantation. KS in
      pediatric liver transplant recipients has low incidence and poor prognosis. We
      report the clinical presentation of a KS in lymph node following HHV-8 infection
      in a pediatric patient presenting four months after liver transplantation. He had
      a good outcome with suspension of tacrolimus and conversion to sirolimus one
      month after diagnosis. To our knowledge, this is the frst KS reported case in our
      country after liver transplant in a pediatric recipient and we believe that this
      entity should be taken into consideration in the differential diagnosis of post
      transplant complications.

PMID- 24092039
TI  - [Alopecia areata].

PMID- 24092040
TI  - Fetal and neonatal mortality in patients with isolated congenital heart diseases
      and heart conditions associated with extracardiac abnormalities.
AB  - Congenital malformations are a known cause of intrauterine death; of them,
      congenital heart diseases (CHDs) are accountable for the highest fetal and
      neonatal mortality rates. They are strongly associated with other extracardiac
      malformations and an early fetal mortality. Two hundred and twenty fves cases of
      CHDs are presented. Of them, 155 were isolated CHDs (group A) and 70 were
      associated with extracardiac malformations, chromosomal disorders, or genetic
      syndromes (group B). The overall mortality in group B was higher than that
      observed in group A (p <0.01). Prenatal mortality was similar in both groups: A:
      8.4% (13 out of 155); B: 15.7% (11 out of 70). Postnatal mortality was A: 16.8%
      (26 out of 155) (p <0.01), OR: 0.52 (95% CI: 0.16-1.7); B: 32.9% (23 out of 70)
      (p <0.01), OR: 0.41 (95% CI: 0.20-0.83). Heart diseases associated with
      extracardiac abnormalities had a higher mortality rate than isolated congenital
      heart diseases in the period up to 60 weeks of postmenstrual age (140 days post
      term). No differences were observed between both groups of patients in terms of
      prenatal mortality. 

PMID- 24092041
TI  - [Successful treatment with prednisone in a critical ill newborn with symptomatic
      multifocal infantile hepatic hemangioendothelioma].
AB  - Infantile hepatic hemangioendothelioma is the most common vascular tumor of the
      liver in infancy. The diagnosis can be enunciated without histological defnition,
      if the clinical, analytical and images fndings are very suggestive; particularly
      in children less than six months old, because the biopsy is not exempt of
      complications. We report a female patient, four days old and 3500 g, who
      developed a hypovolemic shock as a complication of the biopsy from a multifocal
      infantile hepatic hemangioendothelioma. She developed clinical manifestations of
      cardiac failure and thrombocytopenia. Because of the critical clinical status we
      choose the medical treatment with prednisone which was administered for fve month
      and complete remission of the tumor was obtained. We highlight the Doppler
      ultrasonography as a safe and no invasive diagnosis method. Management of this
      disease is commented as well. 

PMID- 24092042
TI  - Radiographic landmarks for locating the femoral origin of the superficial medial
      collateral ligament.
AB  - BACKGROUND: Little has been written about the use of radiographic landmarks for
      locating the origin of the superficial medial collateral ligament (sMCL). A
      standardized radiographic landmark for the sMCL origin using intraoperative
      fluoroscopic imaging may be of value in aiding the surgeon in accurate femoral
      tunnel placement in the setting of extensive soft tissue disruption and bony
      attrition. PURPOSE: To determine a reproducible radiographic landmark that will
      assist in correct femoral tunnel placement in sMCL repair and reconstruction.
      STUDY DESIGN: Descriptive laboratory study. METHODS: Ten fresh-frozen unmatched
      human cadaveric knees were dissected, and the origin of the sMCL was exposed. A 2
      mm metallic marker was then placed at the center of the femoral origin of the
      sMCL. True lateral fluoroscopically assisted digital radiographs were obtained of
      the knee with the posterior and distal femoral condyles overlapping in a
      standardized fashion. With the use of computer software, reference lines were
      drawn on the images, creating 4 quadrants. Two independent examiners performed
      quantitative measurements of the sMCL origin in relation to this axis and to the
      Blumensaat line. RESULTS: Mean measurements showed the sMCL origin to be closely
      related to the intersection point of the Blumensaat line and a line drawn
      distally from the posterior femoral cortex on a true lateral radiograph. The sMCL
      origin was found at a mean point 1.6 +/- 4.3 mm posterior and 4.9 +/- 2.1 mm
      proximal to the intersection of a line paralleling the posterior femoral cortex
      and a line drawn perpendicular to the posterior femoral cortical line, where it
      intersects the Blumensaat line. In 5 of 10 specimens, the center of the sMCL
      origin fell precisely on the Blumensaat line. The remaining specimens had sMCL
      origins anterior to the Blumensaat line. The femoral origin of the sMCL was found
      in the proximal and posterior quadrants in 8 of 10 specimens. CONCLUSION: With a
      relatively small amount of deviation, the sMCL origin can be consistently
      identified on a true lateral radiograph of the knee using reproducible reference
      lines on fluoroscopic imaging. CLINICAL RELEVANCE: Accurate identification of the
      femoral origin of the sMCL can be accomplished by intraoperative fluoroscopic
      imaging. This information may be of significant benefit in repairing acute
      injuries and in reconstructive procedures complicated by bony attrition and soft
      tissue loss.

PMID- 24092043
TI  - Kinematic analysis of the posterior cruciate ligament, part 2: a comparison of
      anatomic single- versus double-bundle reconstruction.
AB  - BACKGROUND: A more thorough understanding of the posterior cruciate ligament
      (PCL) has led to an increase in awareness and treatment of complex PCL injuries.
      Controversy exists about whether PCL reconstruction (PCLR) using an anatomic
      single-bundle (aSB) or anatomic double-bundle (aDB) technique is the most
      effective. HYPOTHESIS: An aDB PCLR provides significantly better anterior
      posterior and rotatory knee stability compared with an aSB PCLR and more closely
      recreates normal knee kinematics. STUDY DESIGN: Controlled laboratory study.
      METHODS: A total of 18 match-paired, cadaveric knees (mean age, 54.8 years;
      range, 51-59 years; 5 male and 4 female pairs) were used to evaluate the
      kinematics of an intact PCL, an aSB and aDB PCLR, and a complete sectioned PCL. A
      6 degrees of freedom robotic system was used to assess knee stability with a 134
      N applied posterior tibial load, 5-N.m external and internal rotation torques, 10
      N.m valgus and varus rotation torques, and a coupled 100-N posterior tibial load
      and 5-N.m external rotation torque at 0 degrees , 15 degrees , 30 degrees , 45
      degrees , 60 degrees , 75 degrees , 90 degrees , 105 degrees , and 120 degrees .
      RESULTS: The aDB PCLR had significantly less posterior translation than the aSB
      PCLR at all flexion angles of 15 degrees  and greater. The largest difference in
      posterior translation was seen at 105 degrees  of flexion, where the aSB PCLR had
      5.3 mm (P = .017) more posterior translation than the aDB PCLR. The aDB PCLR also
      had significantly less internal rotation than the aSB PCLR at all tested angles
      of 90 degrees  and greater. Neither reconstruction was able to fully restore
      native knee kinematics. CONCLUSION: An aDB PCLR more closely approximated native
      knee kinematics when compared with an aSB PCLR. Specifically, the aDB PCLR
      demonstrated significantly more restraint to posterior translation at flexion
      angles between 15 degrees  and 120 degrees  and less internal rotational laxity
      at high flexion angles 90 degrees  to 120 degrees . CLINICAL RELEVANCE:
      Comparison of the 2 reconstruction techniques illustrates the time-zero kinematic
      advantage imparted by the addition of the posteromedial bundle reconstruction.
      The benefit is most pertinent for resistance to posterior translation across a
      full range of flexion and rotational stability beyond 90 degrees  of knee
      flexion.

PMID- 24092044
TI  - Quantitative regional validation of the visual rating scale for posterior
      cortical atrophy.
AB  - OBJECTIVES: Validate the four-point visual rating scale for posterior cortical
      atrophy (PCA) on magnetic resonance images (MRI) through quantitative grey matter
      (GM) volumetry and voxel-based morphometry (VBM) to justify its use in clinical
      practice. METHODS: Two hundred twenty-nine patients with probable Alzheimer's
      disease and 128 with subjective memory complaints underwent 3T MRI. PCA was rated
      according to the visual rating scale. GM volumes of six posterior structures and
      the total posterior region were extracted using IBASPM and compared among PCA
      groups. To determine which anatomical regions contributed most to the visual
      scores, we used binary logistic regression. VBM compared local GM density among
      groups. RESULTS: Patients were categorised according to their PCA scores: PCA-0
      (n = 122), PCA-1 (n = 143), PCA-2 (n = 79), and PCA-3 (n = 13). All structures
      except the posterior cingulate differed significantly among groups. The inferior
      parietal gyrus volume discriminated the most between rating scale levels. VBM
      showed that PCA-1 had a lower GM volume than PCA-0 in the parietal region and
      other brain regions, whereas between PCA-1 and PCA-2/3 GM atrophy was mostly
      restricted to posterior regions. CONCLUSIONS: The visual PCA rating scale is
      quantitatively validated and reliably reflects GM atrophy in parietal regions,
      making it a valuable tool for the daily radiological assessment of dementia. KEY
      POINTS: * Visual rating scale reflects grey matter atrophy in posterior brain
      regions. * Different PCA scores corresponded well to different quantitative
      degrees of atrophy. * Inferior parietal gyrus volume influenced assessment based
      on the visual rating scale. * This simple visual rating scale makes it useful for
      radiological dementia assessment.

PMID- 24092045
TI  - Dual energy MDCT assessment of renal lesions: an overview.
AB  - With the expansion of cross-sectional imaging, the number of renal lesions that
      are incidentally discovered has increased. Multidetector CT (MDCT) is the
      investigation of choice for characterising and staging renal lesions. Although a
      definitive diagnosis can be confidently posed for most of them, a number of renal
      lesions remain indeterminate following MDCT. Further imaging tests are therefore
      needed, with subsequent increase of healthcare costs, radiation exposure, and
      patient anxiety. By addressing most of the issues with conventional MDCT imaging,
      dual-energy MDCT can improve the diagnosis of renal lesions and, potentially, may
      represent a paradigm shift from a merely attenuation-based to a material-specific
      spectral imaging investigation. The purpose of this review is to provide an
      overview of current clinical applications of dual-energy CT in the evaluation of
      renal lesions. Key Points * As MDCT expands, an increasing number of renal
      lesions are serendipitously discovered. * With conventional MDCT, technical
      issues affect the diagnosis of renal lesions. * Dual-energy CT addresses some of
      the drawbacks of conventional MDCT. * Dual-energy CT may represent a paradigm
      shift for renal lesions imaging. 

PMID- 24092047
TI  - Pathologically determined tumor volume vs pathologic T stage in the prediction of
      outcome after surgical treatment of oropharyngeal squamous cell carcinoma.
AB  - IMPORTANCE: Traditional prognostic models for squamous cell carcinoma of the head
      and neck are based on the TNM staging system. However, there is growing evidence
      that tumor volume (TV) may be a more accurate predictor of outcome. OBJECTIVE: To
      determine whether pathologic TV (pTV) in patients with oropharyngeal squamous
      cell carcinoma treated surgically is a more significant predictor of outcome
      compared with pathologic tumor (pT) stage. DESIGN, SETTING, AND PARTICIPANTS:
      Review of patients whose treatment was managed between January 1, 1985, and
      December 2005 at a US tertiary referral cancer center. The participants included
      159 patients who had undergone primary surgery for oropharyngeal squamous cell
      carcinoma and had 3 dimensions reported on histopathologic testing. MAIN OUTCOMES
      AND MEASURES: The pTV was calculated as the product of the 3 dimensions expressed
      in cubic centimeters. For comparison of pT stage with pTV in outcome prediction,
      concordance indexes were generated using the bootstrap method (n = 1000) to
      quantify the predictive accuracy of recurrence and survival outcomes. Concordance
      indexes were then compared and a significant difference was considered when P <
      .05. RESULTS: The median age of the patients was 59 years (range, 22-84 years)
      and 106 were male (67%). Sites of the tumors were base of the tongue (86 patients
      [54%]), tonsil (48 [30%]), soft palate (24 [15%]), and posterior pharyngeal wall
      (1 [1%]). The median follow-up time was 64 months (range, 1-272 months). The
      median tumor volume was 6.8 cm3 (range, 0.1-162.5 cm3). Pathologic TV was a
      significant predictor of disease-specific mortality. Unlike pT stage, pTV was a
      significant predictor of local recurrence, regional recurrence, and distant
      recurrence. Comparison of concordance indexes showed that pTV was a significantly
      better predictor of disease-specific mortality, local recurrence, and distant
      recurrence (all P < .05). CONCLUSIONS AND RELEVANCE: Pathologic TV outperforms pT
      stage in the prediction of outcome following surgical treatment of oropharyngeal
      cancer. Tumor volume should be considered in the design of prospective surgical
      trials.

PMID- 24092046
TI  - Bimodal voltage dependence of TRPA1: mutations of a key pore helix residue reveal
      strong intrinsic voltage-dependent inactivation.
AB  - Transient receptor potential A1 (TRPA1) is implicated in somatosensory processing
      and pathological pain sensation. Although not strictly voltage-gated, ionic
      currents of TRPA1 typically rectify outwardly, indicating channel activation at
      depolarized membrane potentials. However, some reports also showed TRPA1
      inactivation at high positive potentials, implicating voltage-dependent
      inactivation. Here we report a conserved leucine residue, L906, in the putative
      pore helix, which strongly impacts the voltage dependency of TRPA1. Mutation of
      the leucine to cysteine (L906C) converted the channel from outward to inward
      rectification independent of divalent cations and irrespective to stimulation by
      allyl isothiocyanate. The mutant, but not the wild-type channel, displayed
      exclusively voltage-dependent inactivation at positive potentials. The L906C
      mutation also exhibited reduced sensitivity to inhibition by TRPA1 blockers,
      HC030031 and ruthenium red. Further mutagenesis of the leucine to all natural
      amino acids individually revealed that most substitutions at L906 (15/19)
      resulted in inward rectification, with exceptions of three amino acids that
      dramatically reduced channel activity and one, methionine, which mimicked the
      wild-type channel. Our data are plausibly explained by a bimodal gating model
      involving both voltage-dependent activation and inactivation of TRPA1. We propose
      that the key pore helix residue, L906, plays an essential role in responding to
      the voltage-dependent gating. 

PMID- 24092048
TI  - X-ray scattering experiments with high-flux X-ray source coupled rapid mixing
      microchannel device and their potential for high-flux neutron scattering
      investigations.
AB  - Small-angle X-ray scattering provides global, shape-sensitive structural
      information about macromolecules in solution. Its extension to time dimension in
      the form of time-resolved SAXS investigations and combination with other time
      resolved biophysical methods contributes immensely to the study of protein
      dynamics. TR-SAXS can also provide unique information about the global structures
      of transient intermediates during protein dynamics. An experimental set-up with
      low protein consumption is essential for an extensive use of TR-SAXS experiments
      on protein dynamics. In this direction, a newly developed 20-microchannel
      microfluidic continuous-flow mixer was combined with SAXS. With this set-up, we
      demonstrate ubiquitin unfolding dynamics after rapid mixing with the chaotropic
      agent Guanidinium-HCl within milliseconds using only ~ 40 nanoliters of the
      protein sample per scattering image. It is suggested that, in the future, this
      new TR-SAXS platform will help to increase the use of time-resolved small-angle X
      ray scattering, wide-angle X-ray scattering and neutron scattering experiments
      for studying protein dynamics in the early millisecond regime. The potential
      research field for this set-up includes protein folding, protein misfolding,
      aggregation in amyloidogenic diseases, function of intrinsically disordered
      proteins and various protein-ligand interactions. 

PMID- 24092050
TI  - Reduced-intensity conditioning regimen with low-dose ATG-F for unrelated bone
      marrow transplant is associated with lower non-relapse mortality than a regimen
      with low-dose TBI: a single-center retrospective analysis of 103 cases.
AB  - Although anti-T lymphocyte globulin-Fresenius (ATG-F) is commonly used as
      prophylaxis for graft-versus-host disease (GVHD), the appropriate dosage of ATG-F
      in the setting of a reduced-intensity conditioning (RIC) regimen has not been
      determined. In the present study, we retrospectively analyzed the clinical
      outcomes of 103 patients after unrelated bone marrow transplant (uBMT) with RIC
      regimens. RIC regimens consisted of purine analogue plus busulfan with low-dose
      TBI or ATG-F (5-10 mg/kg in total). Median age was 57 years (range 20-68). The
      incidence of grade II-IV acute GVHD and chronic GVHD with ATG-F was significantly
      lower than that with TBI 2 Gy (15 vs. 61 %, P < 0.05; 33 vs. 57 %, P < 0.05). The
      incidence of 2-year NRM with ATG-F was significantly lower than that with TBI 2
      Gy (6 vs. 28 %, P < 0.05). There was no statistically significant difference in
      the cumulative incidence of 2-year relapse between the ATG-F and TBI 2 Gy groups
      (37 vs. 20 %, P = 0.13). In conclusion, the addition of low-dose ATG-F to GVHD
      prophylaxis in patients who received uBMT resulted in decreased incidence of
      acute and chronic GVHD, which led to a significantly reduced risk of NRM without
      compromising overall survival. The beneficial effect of low-dose ATG-F should be
      assessed in a prospective clinical trial.

PMID- 24092049
TI  - Periconceptional folic acid associated with an increased risk of oral clefts
      relative to non-folate related malformations in the Northern Netherlands: a
      population based case-control study.
AB  - Periconceptional folic acid has been associated with a reduced risk of neural
      tube defects, but findings on its effect in oral clefts are largely inconclusive.
      This case-control study assesses the effects of periconceptional folic acid on
      cleft risk, using complementary data from the Dutch Oral Cleft Registry and a
      population-based birth defects registry (Eurocat) of children and foetuses born
      in the Northern Netherlands between 1997 and 2009. Cases were live-born infants
      with non-syndromic clefts (n = 367) and controls were infants or foetuses with
      chromosomal/syndromal (n = 924) or non-folate related anomalies (n = 2,021). We
      analyzed type/timing/duration of supplement use related to traditional cleft
      categories as well as to their timing (early/late embryonic periods) and
      underlying embryological processes (fusion/differentiation defects). Consistent
      supplement use during the aetiologically relevant period (weeks 0-12
      postconception) was associated with an increased risk of clefts (adjusted odds
      ratio 1.72, 95% confidence interval 1.19-2.49), especially of cleft lip/alveolus
      (3.16, 1.69-5.91). Further analysis systematically showed twofold to threefold
      increased risks for late differentiation defects-mainly clefts of the
      lip/alveolus-with no significant associations for early/late fusion defects.
      Effects were attributable to folic acid and not to other multivitamin components,
      and inclusion of partial use (not covering the complete aetiologically relevant
      period) generally weakened associations. In conclusion, this study presents
      several lines of evidence indicating that periconceptional folic acid in the
      Northern Netherlands is associated with an increased risk of clefts, in
      particular of cleft lip/alveolus. This association is strengthened by the
      specificity, consistency, systematic pattern, and duration of exposure-response
      relationship of our findings, underlining the need to evaluate public health
      strategies regarding folic acid and to further investigate potential adverse
      effects.

PMID- 24092051
TI  - Microfluidic preparation of liposomes to determine particle size influence on
      cellular uptake mechanisms.
AB  - PURPOSE: This study investigates the cellular uptake and trafficking of liposomes
      in Caco-2 cells, using vesicles with distinct average diameters ranging from 40.6
      nm to 276.6 nm. Liposomes were prepared by microfluidic hydrodynamic flow
      focusing, producing nearly-monodisperse populations and enabling size-dependent
      uptake to be effectively evaluated. METHODS: Populations of PEG-conjugated
      liposomes of various distinct sizes were prepared in a disposable microfluidic
      device using a simple continuous-flow microfluidic technique. Liposome cellular
      uptake was investigated using flow cytometry and confocal microscopy. RESULTS:
      Liposome uptake by Caco-2 cells was observed to be strongly size-dependent for
      liposomes with mean diameters ranging from 40.6 nm to 276.6 nm. When testing
      these liposomes against endocytosis inhibitors, cellular uptake of the largest
      (97.8 nm and 162.1 nm in diameter) liposomes were predominantly subjected to
      clathrin-dependent uptake mechanisms, the medium-sized (72.3 nm in diameter)
      liposomes seemed to be influenced by all investigated pathways and the smallest
      liposomes (40.6 nm in diameter) primarily followed a dynamin-dependent pathway.
      In addition, the 40.6 nm, 72.3 nm, and 162.1 nm diameter liposomes showed
      slightly decreased accumulation within endosomes after 1 h compared to liposomes
      which were 97.8 nm in diameter. Conversely, liposome co-localization with
      lysosomes was consistent for liposomes ranging from 40.6 nm to 97.8 nm in
      diameter. CONCLUSIONS: The continuous-flow synthesis of nearly-monodisperse
      populations of liposomes of distinct size via a microfluidic hydrodynamic flow
      focusing technique enabled unique in vitro studies in which specific effects of
      particle size on cellular uptake were elucidated. The results of this study
      highlight the significant influence of liposome size on cellular uptake
      mechanisms and may be further exploited for increasing specificity, improving
      efficacy, and reducing toxicity of liposomal drug delivery systems.

PMID- 24092052
TI  - Bayesian approach to estimate AUC, partition coefficient and drug targeting index
      for studies with serial sacrifice design.
AB  - PURPOSE: The current study presents a Bayesian approach to non-compartmental
      analysis (NCA), which provides the accurate and precise estimate of AUC 0
      (infinity) and any AUC 0 (infinity) -based NCA parameter or derivation. METHODS:
      In order to assess the performance of the proposed method, 1,000 simulated
      datasets were generated in different scenarios. A Bayesian method was used to
      estimate the tissue and plasma AUC 0 (infinity) s and the tissue-to-plasma AUC 0
      (infinity) ratio. The posterior medians and the coverage of 95% credible
      intervals for the true parameter values were examined. The method was applied to
      laboratory data from a mice brain distribution study with serial sacrifice design
      for illustration. RESULTS: Bayesian NCA approach is accurate and precise in point
      estimation of the AUC 0 (infinity) and the partition coefficient under a serial
      sacrifice design. It also provides a consistently good variance estimate, even
      considering the variability of the data and the physiological structure of the
      pharmacokinetic model. The application in the case study obtained a
      physiologically reasonable posterior distribution of AUC, with a posterior median
      close to the value estimated by classic Bailer-type methods. CONCLUSIONS: This
      Bayesian NCA approach for sparse data analysis provides statistical inference on
      the variability of AUC 0 (infinity) -based parameters such as partition
      coefficient and drug targeting index, so that the comparison of these parameters
      following destructive sampling becomes statistically feasible.

PMID- 24092053
TI  - Population PKPD modeling of BACE1 inhibitor-induced reduction in Abeta levels in
      vivo and correlation to in vitro potency in primary cortical neurons from mouse
      and guinea pig.
AB  - PURPOSE: The aims were to quantify the in vivo time-course between the oral dose,
      the plasma and brain exposure and the inhibitory effect on Amyloid beta (Abeta)
      in brain and cerebrospinal fluid, and to establish the correlation between in
      vitro and in vivo potency of novel beta-secretase (BACE1) inhibitors. METHODS:
      BACE1-mediated inhibition of Abeta was quantified in in vivo dose- and/or time
      response studies and in vitro in SH-SY5Y cells, N2A cells, and primary cortical
      neurons (PCN). An indirect response model with inhibition on Abeta production
      rate was used to estimate unbound in vivo IC 50 in a population pharmacokinetic
      pharmacodynamic modeling approach. RESULTS: Estimated in vivo inhibitory
      potencies varied between 1 and 1,000 nM. The turnover half-life of Abeta40 in
      brain was predicted to be 0.5 h in mouse and 1 h in guinea pig. An excellent
      correlation between PCN and in vivo potency was observed. Moreover, a strong
      correlation in potency was found between human SH-SY5Y cells and mouse PCN, being
      4.5-fold larger in SH-SY5Y cells. CONCLUSION: The strong in vivo-in vitro
      correlation increased the confidence in using human cell lines for screening and
      optimization of BACE1 inhibitors. This can optimize the design and reduce the
      number of preclinical in vivo effect studies.

PMID- 24092054
TI  - Glyceride lipid formulations: molecular dynamics modeling of phase behavior
      during dispersion and molecular interactions between drugs and excipients.
AB  - PURPOSE: Little is known about the microstructure of lipid-based formulations, or
      how their structure changes as they disperse in the lumen of the gastrointestinal
      tract. We used molecular dynamics (MD) simulation to study such formulations at
      the molecular level as they interact with water during dispersion. METHODS: We
      studied a simple lipid formulation, by itself and in the presence of drugs. The
      formulation contained mono- and di-lauroyl glycerides at 0-75% (w)/w water.
      Acyclovir, danazol, hydrocortisone, ketoprofen or progesterone, were included to
      investigate their dynamic behavior and localization during dispersion. RESULTS:
      Micro-structuring of the formulation was evident at all water concentrations. As
      the water content increased, the microstructure evolved from a continuous phase
      containing isolated water molecules, to a reverse micellar solution and finally
      to a system containing lamellar lipids with large pools of free water. Drugs
      partitioned into the aqueous and lipid domains principally under the influence of
      hydrogen bonding and hydrophobic interactions. Drugs located preferentially to
      the interfaces between water and lipid where they are able to make both
      hydrophobic and hydrophilic interactions. CONCLUSION: Molecular dynamics
      simulations offer an unprecedented view of the structure of lipid-based
      formulations and has considerable potential as an in silico tool for formulators.

PMID- 24092056
TI  - The benefits and risks of risk-adjustment in paediatric cardiac surgery.

PMID- 24092055
TI  - Breast cancer resistance protein-mediated efflux of luteolin glucuronides in HeLa
      cells overexpressing UDP-glucuronosyltransferase 1A9.
AB  - PURPOSE: UDP-glucuronosyltransferases (UGTs) are responsible for the formation of
      glucuronides of polyphenolic flavonoids. This study investigated the UGT1A9
      mediated glucuronidation of luteolin and the kinetics of luteolin glucuronide
      efflux. METHOD: HeLa cells overexpressing UGT1A9 (HeLa-UGT1A9) were used to
      determine the kinetics of breast cancer resistance protein (BCRP)-mediated
      transport of luteolin glucuronides. Human UGT isoforms were used to determine
      glucuronidation rates. RESULTS: UGT1A9 was found to catalyze the production of
      four luteolin glucuronides, including three known monoglucuronides and a novel
      3', 4'-diglucuronide. Ko143, a potent specific inhibitor of BCRP, significantly
      inhibited efflux of luteolin monoglucuronides from HeLa1A9 cells and increased
      their intracellular levels in a dose-dependent manner. The formation of luteolin
      diglucuronide was observed when intracellular concentration of total
      monoglucuronides went above 0.07 nM. CONCLUSIONS: Intracellular accumulation of
      diglucuronide was detected at high monoglucuronide concentrations (>0.07 nM).
      Diglucuronide production is speculated to be a compensatory pathway for luteolin
      disposition.

PMID- 24092057
TI  - Ethnic differences in the cost-effectiveness of targeted and mass screening for
      high cardiovascular risk in the UK: cross-sectional study.
AB  - OBJECTIVES: To investigate ethnic differences in the cost-effectiveness of
      targeted and mass screening for high cardiovascular risk. DESIGN: Simulation of
      two screening strategies (targeted screening of most deprived areas and mass
      screening) using cross-sectional data from Health Survey for England. SETTING:
      England. SUBJECTS: 9407 adults aged 40-74 years (493 Black Caribbean, 532 Indian,
      516 Pakistani/Bangladeshi, 617 Irish and 7249 general population of whom 6633
      were White). MAIN OUTCOME MEASURES: Coverage of high-risk population, number
      needed to screen to identify one person at high cardiovascular risk and cost
      effectiveness of targeted screening, with incremental analysis of expanding
      targeted to mass screening. RESULTS: Coverage, number needed to screen and cost
      effectiveness of targeted screening were better in all ethnic minority groups
      compared with the White group and general population. Targeted screening would
      identify 19.2% of high-risk individuals in the general population, and require
      4.1 people to be screened to identify one person at high cardiovascular risk at a
      cost of L98. In the Pakistani/Bangladeshi group, 68.7% of the high-risk
      population would be identified, and only 2.5 people would need to be screened at
      a lower cost of L59. In comparison with targeted screening, mass screening was
      less cost-effective overall but the cost per additional high-risk individual
      detected was the lowest among the South Asian groups (Indian L130 and
      Pakistani/Bangladeshi L94). CONCLUSIONS: Irrespective of whether cardiovascular
      screening is targeted or universal, it is more cost-effective in South Asian
      ethnic groups than in the general population. Therefore, cardiovascular screening
      has the potential to reduce ethnic health inequalities.

PMID- 24092230
TI  - Diagnostic accuracy of 18F choline PET/CT using time-of-flight reconstruction
      algorithm in prostate cancer patients with biochemical recurrence.
AB  - PURPOSE: Image quality (IQ) of PET in voluminous body regions can be limited,
      which impairs the assessment of small metastatic lesions. Time-of-flight (TOF)
      reconstruction algorithm may deliver an increase of spatial resolution. The
      purpose of this study was to evaluate the impact of TOF on IQ, lesion detection
      rate, lesion volume (V) and SUVmax in F choline PET/CT of prostate cancer
      patients with biochemical recurrence compared to standard PET/CT reconstruction
      (standard). PATIENTS AND MATERIALS: During a period of 9 months, 32 patients with
      prostate cancer (mean [SD] age, 71 [7.8] years) and biochemical recurrence were
      included in this prospective institutional review board-approved study. Each
      patient underwent a state-of-the-art 3-dimensional F choline PET/CT. A total of
      76 lesions were assessed by 2 board-certified nuclear medicine physicians and a
      third-year resident. Lesion volume and SUVmax of local recurrence, lymph nodes,
      and organ metastases were compared between TOF and standard. Image quality and
      lesion demarcation were rated according to a 5-point Likert-type scale.
      Interobserver agreement was assessed. RESULTS: Eight additional lesions were
      detected using TOF (SUVmax, 3.64 [0.95]; V, 0.58 cm [0.50]). Image quality was
      reduced (IQ standard, 1.28; TOF, 1.77; P < 0.01) in calculated TOF images,
      although quality of lesion demarcation was improved (lesion demarcation:
      standard, 1.66; TOF, 1.26; P < 0.01). SUVmax was significantly increased in TOF
      images (SUVmax standard, 6.9 [4.1]; TOF, 8.1 [4.1]; P < 0.01), whereas V did not
      show significant differences (V standard, 5.3 [10.4] cm; TOF, 5.4 [10.3] cm; P =
      0.41). Interobserver agreement was good for combined ratings (1 + 2 and 3 + 4).
      CONCLUSIONS: Application of TOF seems to be of additional value to detect small
      metastatic lesions in patients with prostate cancer and biochemical recurrence,
      which may have further clinical implications for secondary treatment.

PMID- 24092058
TI  - The expression of cytokeratin in keratocystic odontogenic tumor, orthokeratinized
      odontogenic cyst, dentigerous cyst, radicular cyst and dermoid cyst.
AB  - The epithelial lining of odontogenic keratocysts exhibits either parakeratosis or
      orthokeratosis. In 2005, the WHO classified odontogenic keratocysts with
      parakeratosis as keratocystic odontogenic tumors (KCOT). Odontogenic keratocysts
      with orthokeratosis were not classified as odontogenic tumors, but instead
      referred to as orthokeratinized odontogenic cysts (OOC). To clarify the
      difference between these two lesions, we investigated their biological
      characteristics using immunohistochemical studies for cytokeratins (CK) in KCOT
      and OOC as well as in dentigerous cysts (DC), radicular cysts (RC) and dermoid
      cysts (DMC). We examined twenty-five cases of KCOT, fifteen cases each of OOC, DC
      and RC, and ten cases of DMC. We studied the immunohistochemical expression of
      CK10, 13, 17 and 19. To evaluate the immunohistochemical staining pattern, we
      divided the epithelial lining of the lesions into three layers (surface layer:
      su, spinous layer: sp, basal layer: ba). For CK10, most OOC and DMC specimens of
      su and sp were positive. For CK13 and 19, most KCOT, DC and RC specimens of su
      and sp were positive. For CK17, most KCOT specimens of su and sp were positive.
      The percentages of total CK expression of su and sp, and ba of CK19 differed
      significantly between the lesions (P < 0.001). These results support the
      hypothesis that OOC originate from not the odontogenic apparatus, but the oral
      epithelial component.

PMID- 24092231
TI  - FDG PET/CT and enhanced CT imaging of tumor heterogeneity in hepatocellular
      carcinoma: imaging-pathologic correlation.
AB  - Tumor heterogeneity is used to define the appearance of different histological
      differentiation within a single neoplasm. We present a case of single
      hepatocellular carcinoma showing both low and high FDG uptake areas. The low FDG
      uptake area was corresponding to low-grade HCC, and the high FDG uptake area was
      corresponding to high-grade HCC. This case indicates that the tumor grades affect
      intratumoral heterogeneity in FDG distribution. FDG PET/CT can be useful for
      guiding tissue sampling of the HCC with heterogeneous histological
      differentiations, and obviating overestimation or underestimation of the
      proportion of the higher-risk cell population. 

PMID- 24092232
TI  - Spacer-armed copper(II) complexes with benzenecarboxylic acids and
      trifluoroacetylacetone aroylhydrazones.
AB  - New bi- and trinuclear copper(ii) complexes of aroylhydrazones of TFA and
      benzenecarboxylic acids were synthesized and characterized. Despite long range
      intramolecular CuCu distances of about 10 A, exchange couplings between
      paramagnetic centres are observed with J values of 0.33 and 0.37 cm(-1) in
      binuclear complexes, and -0.33 cm(-1) in trinuclear complexes. Seven hyperfine
      peaks with a value of aCu = 37.0 * 10(-4) cm(-1) are observed in EPR spectra of
      binuclear complexes. The possible mechanisms responsible for the observed weak
      long range coupling via aromatic spacers are discussed. 

PMID- 24092233
TI  - Fast and accurate computational modeling of adsorption on graphene: a dispersion
      interaction challenge.
AB  - Understanding molecular interactions of graphene is a question of key importance
      to design new materials and catalytic systems for practical usage. Although for
      small models good accuracy was demonstrated in theoretical analysis with ab
      initio and density functional methods, the application to real-size systems with
      thousands of atoms is currently hardly possible on routine bases due to the high
      computational cost. In the present study we report that incorporation of
      dispersion correction led to the principal improvement in the description of
      graphene systems at a semi-empirical level. The accuracy and the scope of the
      calculations were explored for a wide range of molecules adsorbed on graphene
      surfaces (H2, N2, CO, CO2, NH3, CH4, H2O, benzene, naphthalene, coronene, ovalene
      and cyclohexane). As a challenging parameter, the calculated adsorption energy of
      aromatic hydrocarbons on graphene Eads = -1.8 +/- 0.1 kcal mol(-1) (per one
      carbon atom) at the PM6-DH2 level was in excellent agreement with the
      experimentally determined value of Eads = -1.7 +/- 0.3 kcal mol(-1). The
      dispersion corrected semi-empirical method was found to be a remarkable
      computational tool suitable for everyday laboratory studies of real-size graphene
      systems. Significant performance improvement (ca. 10(3) times faster) and
      excellent accuracy were found as compared to the omegaB97X-D density functional
      calculations. 

PMID- 24092234
TI  - Radiation-induced cardiovascular disease.
AB  - OPINION STATEMENT: Thoracic radiation remains an effective treatment for many
      types of neoplasms. The clinical benefit of radiation therapy on cancer mortality
      is counterbalanced by an increased risk of cardiovascular events in survivors.
      The long-term cardiovascular sequelae of thoracic radiation include premature
      coronary artery disease, valvular disease, pericardial disease, myocardial
      disease with systolic and especially diastolic dysfunction, and conduction system
      abnormalities. Radiation heart disease progresses over time and may manifest
      decades after the initial exposure. Since the risk of cardiac complications is
      significantly increased following chest irradiation, appropriate screening and
      long-term cardiac follow-up of these patients is essential. This article will
      summarize the pathophysiological features, clinical presentations, and current
      recommendations for screening and prevention of the wide spectrum of radiation
      induced cardiovascular disease.

PMID- 24092235
TI  - Hemi-body port-wine stains and progressive paresis due to territorial
      perineuriomas.
AB  - We present a case of a biopsy-proven intraneural perineurioma involving the left
      lumbosacral and brachial plexus with prominent hemi-body port wine stains in the
      associated dermatomes. The relationship between the two entities is not clear,
      but this case may provide a clue to understanding the etiological pathogenesis of
      intraneural perineurioma in the future. 

PMID- 24092236
TI  - Alveolar soft-part sarcoma in the sacrum: a case report and review of the
      literature.
AB  - Alveolar soft part sarcoma (ASPS) is a rare disease of the soft tissue. Although
      the disease is rare, it is refractory to chemotherapy and radiation. En bloc
      surgical resection offers the best chance of cure. In this article we report the
      case of a 28-year-old woman who presented with buttock and leg pain, bowel,
      bladder and gait impairment and a large mass in the sacrum. Following surgical
      excision, the lesion was proven to be ASPS. On pathology, the mass was TFE3
      (transcription factor E3) positive, indicating the presence of the ASPL-TFE3
      (novel gene-transcription factor) translocation. Following surgery, the patient
      had improvement in her pain and ambulation; however, she refused adjuvant therapy
      to pursue hospice care and succumbed to her disease 2 years after surgery. On a
      review of the literature, it was found that ASPS of the bone constitutes a rare
      and formidable subset of this disease. Further, metastases related to ASPS are
      common in the lungs, liver, brain, and lymph nodes. The degree of dissemination
      is a predictor of outcome, with 5-year survival of 81-88% in patients with local
      disease and only 20-46% in patients with metastatic disease at the time of
      presentation. Brain metastases at the time of presentation portend the worst
      prognosis.

PMID- 24092237
TI  - Quantitative 3D ultrashort time-to-echo (UTE) MRI and micro-CT (MUCT) evaluation
      of the temporomandibular joint (TMJ) condylar morphology.
AB  - OBJECTIVE: Temporomandibular dysfunction involves osteoarthritis of the TMJ,
      including degeneration and morphologic changes of the mandibular condyle. The
      purpose of this study was to determine the accuracy of novel 3D-UTE MRI versus
      micro-CT (MUCT) for quantitative evaluation of mandibular condyle morphology.
      MATERIALS AND METHODS: Nine TMJ condyle specimens were harvested from cadavers (2
      M, 3 F; age 85 +/- 10 years, mean +/- SD). 3D-UTE MRI (TR = 50 ms, TE = 0.05 ms,
      104-MUm isotropic-voxel) was performed using a 3-T MR scanner and MUCT (18-MUm
      isotropic-voxel) was also performed. MR datasets were spatially registered with a
      MUCT dataset. Two observers segmented bony contours of the condyles.
      Fibrocartilage was segmented on the MR dataset. Using a custom program, bone and
      fibrocartilage surface coordinates, Gaussian curvature, volume of segmented
      regions, and fibrocartilage thickness were determined for quantitative evaluation
      of joint morphology. Agreement between techniques (MRI vs. MUCT) and observers
      (MRI vs. MRI) for Gaussian curvature, mean curvature, and segmented volume of the
      bone were determined using intraclass correlation coefficient (ICC) analysis.
      RESULTS: Between MRI and MUCT, the average deviation of surface coordinates was
      0.19 +/- 0.15 mm, slightly higher than the spatial resolution of MRI. Average
      deviation of the Gaussian curvature and volume of segmented regions, from MRI to
      MUCT, was 5.7 +/- 6.5% and 6.6 +/- 6.2%, respectively. ICC coefficients (MRI vs.
      MUCT) for Gaussian curvature, mean curvature, and segmented volumes were 0.892,
      0.893, and 0.972, respectively. Between observers (MRI vs. MRI), the ICC
      coefficients were 0.998, 0.999, and 0.997, respectively. Fibrocartilage thickness
      was 0.55 +/- 0.11 mm, as previously described in the literature for grossly
      normal TMJ samples. CONCLUSIONS: 3D-UTE MR quantitative evaluation of TMJ condyle
      morphology ex-vivo, including surface, curvature, and segmented volume, shows
      high correlation against MUCT and between observers. In addition, UTE MRI allows
      quantitative evaluation of the fibrocartilaginous condylar component.

PMID- 24092238
TI  - MyoD is a tumor suppressor gene in medulloblastoma.
AB  - While medulloblastoma, a pediatric tumor of the cerebellum, is characterized by
      aberrations in developmental pathways, the majority of genetic determinants
      remain unknown. An unbiased Sleeping Beauty transposon screen revealed MyoD as a
      putative medulloblastoma tumor suppressor. This was unexpected, as MyoD is a
      muscle differentiation factor and not previously known to be expressed in
      cerebellum or medulloblastoma. In response to deletion of one allele of MyoD, two
      other Sonic hedgehog-driven mouse medulloblastoma models showed accelerated tumor
      formation and death, confirming MyoD as a tumor suppressor in these models. In
      normal cerebellum, MyoD was expressed in the proliferating granule neuron
      progenitors that are thought to be precursors to medulloblastoma. Similar to some
      other tumor suppressors that are induced in cancer, MyoD was expressed in
      proliferating medulloblastoma cells in three mouse models and in human
      medulloblastoma cases. This suggests that although expression of MyoD in a
      proliferating tumor is insufficient to prevent tumor progression, its expression
      in the cerebellum hinders medulloblastoma genesis.

PMID- 24092239
TI  - Infant cortex responds to other humans from shortly after birth.
AB  - A significant feature of the adult human brain is its ability to selectively
      process information about conspecifics. Much debate has centred on whether this
      specialization is primarily a result of phylogenetic adaptation, or whether the
      brain acquires expertise in processing social stimuli as a result of its being
      born into an intensely social environment. Here we study the haemodynamic
      response in cortical areas of newborns (1-5 days old) while they passively viewed
      dynamic human or mechanical action videos. We observed activation selective to a
      dynamic face stimulus over bilateral posterior temporal cortex, but no activation
      in response to a moving human arm. This selective activation to the social
      stimulus correlated with age in hours over the first few days post partum. Thus,
      even very limited experience of face-to-face interaction with other humans may be
      sufficient to elicit social stimulus activation of relevant cortical regions. 

PMID- 24092240
TI  - Effects of Chinese medicine five-element music on the quality of life for
      advanced cancer patients: a randomized controlled trial.
AB  - OBJECTIVES: To evaluate the effects of the Chinese medicine (CM) five-element
      music on quality of life for senior and non-senior advanced cancer patients.
      METHODS: With a randomized controlled trial, 170 advanced cancer patients were
      randomly assigned to three groups: the CM five-element music group (68 patients),
      the Western music therapy group (68 cases), and the no music therapy group (34
      cases). All patients of 70 years old or older were considered seniors and the
      remaining patients younger than 70 years were considered nonseniors. Patients in
      the CM five-element music group listened to CM five-element music, the patients
      in the Western music group listened to Western music, and the patients in the no
      music group did not listen to music. A course of treatment was 3 weeks, with 30
      min each day, 5 days a week. The Hospice Quality of Life Index-Revised (HQOLI-R)
      and Karnofsky performance score (KPS) were measured in the three groups before
      and after treatment. The symptom diary score was measured in the three groups
      every 3 days, 7 times in total. RESULTS: CM five-element music group showed a
      significant difference of HQOLI-R, KPS and symptom diary score with other groups
      (all P<0.01). There were significant differences of HQOLI-R, symptom diary score,
      and KPS after treatment in CM five-element music group and other groups in the
      non-senior subgroup (P<0.05). Additionally, there were significant differences in
      HQOLI-R and KPS after treatment among the three groups in the senior subgroup
      (P<0.05). CONCLUSIONS: CM five-element music therapy could improve the quality of
      life and KPS for senior and non senior advanced cancer patients, and it could
      improve subjective symptoms for non-senior advanced cancer patients.

PMID- 24092241
TI  - Long-term effect of stent coating with zedoary essential components on neointimal
      formation in the porcine coronary artery.
AB  - OBJECTIVE: To examine the effect of the zedoary essential component-eluting stent
      (ZES) on a porcine coronary neointimal formation. METHODS: ZES, sirolimus-eluting
      stents (SES), and bare metal stents (BMS) were randomly implanted in three
      different major epicardial vessels in 36 balloon-injured pigs. Coronary
      angiography, optical coherence tomography, and histomorphological analysis were
      used to determine antihyperplasia effects. RESULTS: ZES and SES had a
      significantly larger lumen diameter and area, and reduced diameter and area of
      stenosis in arteries at 30 and 90 days compared with arteries implanted with BMS
      (P<0.01). Histomorphometric analysis showed moderate inflammatory responses, such
      as infiltration of mononuclear cells, lymphocytes, and multinucleated giant cells
      in some arteries with SES compared with ZES (P<0.05). Injury scores were not
      different among the three groups at 30 and 90 days. The endothelialization score
      in the SES group was 2.69 +/- 0.42 at 30 days and 2.83 +/- 0.39 at 90 days
      compared with the ZES and BMS groups (both were 3.00 +/- 0.00 at either 30 or 90
      days, P<0.05). Well developed endothelium was observed in the ZES group, while
      incomplete endothelium and inflammatory cells were observed with stent struts
      partly naked at the vessel lumen in the SES group. CONCLUSION: The ZES inhibits
      neointimal hyperplasia with good endothelia coverage in the porcine balloon
      injury coronary model.

PMID- 24092242
TI  - Effects of electro-acupuncture on personality traits in depression: a randomized
      controlled study.
AB  - OBJECTIVE: To explore the personality-adjusting effect of electro-acupuncture
      treatment for depression and compared this treatment with paroxetine treatment.
      METHODS: A non-blinded, randomized controlled trial was adopted. Sixty depressed
      patients, who met trial criteria, were randomly assigned to the treatment and the
      control groups. In the treatment group, electro-acupuncture treatment was used,
      and paroxetine treatment was used in the control group. During the 24-week study
      period, 12 patients dropped out and 48 patients completed the study. The
      Minnesota Multiple Personality Inventory (MMPI) was adopted as the evaluation
      tool. At the same time, the Self-rating Depression Scale (SDS), Self-rating
      Anxiety Scale (SAS) and Montgomery-Asberg Depression Rating Scale (MADRS) were
      used to evaluate the psychological state. Evaluations were done before and after
      treatment. RESULTS: After treatment, patients' psychological state improved
      significantly in both groups (P<0.01). For the treatment group, within-group
      comparison between baseline and after 24 weeks of treatment showed that severity
      of depression had significantly decreased (P<0.01). MADRS and SDS scores
      decreased significantly (P<0.05) and MMPI subscale scores for hypochondriasis,
      depression, psychopathic deviate, psychasthenia, social introversion and fake
      decreased significantly (P<0.05). For the control group, severity of depression
      also decreased significantly. MADRS and SDS scores decreased significantly
      (P<0.05); and MMPI subscale scores for hypochondriasis, depression, hysteria,
      paranoia, and psychasthenia decreased significantly (P<0.05). Between-group
      comparison demonstrated that for the MMPI subscales paranoia and social
      introversion, the decrease of score was greater in the treatment group than in
      the control group (P<0.05). However, there were no other significant differences
      between the control group and the treatment group. CONCLUSION: Electro
      acupuncture is effective for treating depression and affects personality traits.

PMID- 24092243
TI  - Liuwei dihuang pills enhance the effect of Western medicine in treating type 2
      diabetes: A meta-analysis of randomized controlled trials.
AB  - OBJECTIVE: To perform meta-analyses evaluating the efficacy of adding Liuwei
      Dihuang Pills (, LDP) to Western medicine in improving treatment outcomes for
      type 2 diabetes. METHODS: Medline, PubMed, Cochrane Library, and Chinese
      databases, including the Chinese National Knowledge Infrastructure were searched
      to identify eligible studies; i.e., if the study involved a randomized clinical
      trial in which the experimental group combined LDP with Western drugs and the
      control group used the corresponding Western drugs alone to treat type 2
      diabetes. Outcomes were measured in terms of fasting blood glucose (FBG),
      postprandial blood glucose (2hPG) and HbA1c level. Efficacy was also measured by
      using control and response rates. The combined odds ratio (OR), mean difference
      (MD), and 95% confidence intervals (95% CI) were calculated. RESULTS: Studies
      included in the analysis were less adequate than expected in terms of
      methodological quality. A total of 1,609 patients from 18 studies were included.
      We found that adding LDP can lower patients' FBG (MD=0.54 mmol/L, 95% CI [0.15,
      0.93], P=0.007), 2hPG (MD=1.05 mmol/L, 95% CI [0.29, 1.81], P<0.01) and HbA1c
      (MD=0.23, 95% CI [0.02, 0.45], P=0.008). There were also improvements in
      treatment response rates (OR=3.41, 95% CI [2.38, 4.90], P<0.01) and control rates
      (OR=2.47, 95% CI [1.91, 3.20], P<0.01). CONCLUSION: Adding LDP to Western
      medicine might improve treatment outcomes of diabetes, including FBG, 2hPG,
      response rates and control rates.

PMID- 24092245
TI  - Rotors during AF: drivers or bystanders?

PMID- 24092244
TI  - A review on pharmacological and analytical aspects of diosmetin: a concise
      report.
AB  - Plants have been used as a source for food material and natural remedies for the
      treatment of vast range of diseases. Nature provides us remedies for the
      treatment of various types of disorders ranging from simple ailments to
      complicated diseases. Plants are known to possess different pharmacological
      activities due to the presence of various phytoconstituents. Flavonoids are one
      of the main active phytoconstituents found in fruits, vegetables, wines, tea and
      cocoa. Flavonoids exhibit various pharmacological activities such as antioxidant,
      anti-inflammatory, anti-allergic, antibacterial, oestrogenic, cytotoxic
      antitumoural, hepatoprotective, antithrombotic and antiviral activity. Diosmetin
      (3', 5, 7-trihydroxy-4'-methoxyflavone), the aglycone part of the flavonoid
      glycosides diosmin occurs naturally in citrus fruit. Although it is found in
      herbal medicines and plays an important role in the treatment of various
      ailments, only limited scientific researches have been conducted. The aim of this
      review is to collect all available scientific literature published on diosmetin
      and combine it into this paper. This review contains an overview of
      pharmacological activities, isolation techniques and analytical techniques for
      diosmetin. Thus, valuable information provided in the present review will help
      researchers in developing alternative methods for the treatment of diseases from
      diosmetin. 

PMID- 24092246
TI  - The bumpy road to evidence: why many research findings are lost in translation.

PMID- 24092247
TI  - Blood pressure and diabetes: a fatal attraction.

PMID- 24092248
TI  - Trends in the outcomes of percutaneous coronary intervention with the routine
      incorporation of fractional flow reserve in real practice.
AB  - AIMS: We evaluated the impact of the routine use of fractional flow reserve (FFR)
      on the practice and outcomes of percutaneous coronary intervention (PCI). METHODS
      AND RESULTS: Between January 2008 and December 2011, the rate of FFR use during
      PCI increased from 1.9 to 50.7% after the introduction of routine FFR use (P <
      0.001). A total of 5097 patients (2699 patients before and 2398 after the routine
      use of FFR) underwent PCI at an academic hospital in Korea; of those, stent
      implantation was deferred in 475 patients. We used propensity score (PS) matching
      to compare the rates of the primary endpoint [death, myocardial infarction (MI),
      or repeat revascularization] at 1 year the cohort before and after the routine
      use of FFR. In the PS-matched cohort (2178 pairs), the median number of lesions
      per patient was 2 [inter-quartile range (IQR) 1-2] before vs. 2 (IQR 1-2) after
      the routine FFR use (P = 0.68); the median number of stents implanted per patient
      was 2 (IQR 1-3) vs. 1 (IQR 1-2), respectively (P < 0.001). The rates of the
      primary endpoint at 1 year was significantly lower in patients after the routine
      FFR use vs. patients before the routine use of FFR (hazard ratio 0.55; 95%
      confidence interval 0.43-0.70; P < 0.001). This was primarily due to a reduction
      in peri-procedural MI and repeat revascularization. CONCLUSION: Routine
      measurement of FFR in daily practice appeared to be associated with less use of
      stents and an improvement in clinical outcomes. CLINICALTRIALSGOV NUMBER: NCT
      01788592.

PMID- 24092249
TI  - Giant aneurysm of the Valsalva sinus associated with multiple coronary artery
      aneurysms and patent ductus arteriosus.

PMID- 24092250
TI  - Incomplete isolated cleft of the anterior mitral valve: first reported as
      triangular defect.

PMID- 24092251
TI  - Responses to: The codex of science: honesty, precision, and truth-and its
      violations.

PMID- 24092252
TI  - Coronary stent restenosis and occlusion: messages from the dead for the living.

PMID- 24092253
TI  - Modified Grey Model and its application to groundwater flow analysis with limited
      hydrogeological data: a case study of the Nubian Sandstone, Kharga Oasis, Egypt.
AB  - Groundwater flow at Kharga Oasis, located in the western desert of Egypt, was
      previously analyzed using numerical models; however, the lack of basic data often
      limits the implementation of these models, as well as introducing a problem for
      model calibration and validation. The Grey Model (GM) was used to overcome these
      difficulties of data limitation and uncertainty of hydrogeological conditions.
      However, no clear theories exist for selecting the number of input model trends
      and the most suitable values of input parameters. Therefore, in the current
      study, a modification of the GM is newly proposed and called the Modified Grey
      Model (MGM) in an attempt to determine a process for selecting the best input
      models' trends with the appropriate values of input parameters to achieve
      acceptable fitting to observations. The sensitivity analysis results showed that
      the MGM produced more stable results than the GM using a wide range of values for
      input parameters. Moreover, the MGM reduced the calculation time required for
      fitting the measured piezometric level trends by 99.8%. Three development
      scenarios of groundwater withdrawal were proposed that involved either expanding
      the present extraction rate or redistributing the groundwater withdrawal over the
      recent working production wells (RWPWs). The results concluded that the
      groundwater table in the northern part of the oasis could be temporally recovered
      to an economical piezometric level; however, the table in the southern part is
      severely decreased. Therefore, new production wells are recommended to be
      constructed in the southern part far enough from the RWPWs.

PMID- 24092254
TI  - Evaluation of poly-aromatic hydrocarbons (PAHs) in the aquatic species of Suez
      Gulf water along El-Sokhna area to the Suez refineries.
AB  - The Egyptian Red Sea environment especially along El-Sokhna area to the Suez
      refineries (Suez) is severely contaminated with organic compounds, as well as
      overfishing. This may be well contributory to recent serious declines in fish
      stocks. Fish embryos are also particularly vulnerable to oil exposure, even at
      extremely low concentrations of less than one part per billion. Consequently,
      even traces of oil pollution at levels often considered safe for wildlife can
      cause severe damage to fish. Sixteen polycyclic aromatic hydrocarbons (PAHs) were
      investigated in ten fish species of aquatic species by high performance liquid
      chromatography (HPLC). The compositions of PAHs determined in all samples were
      measured in order to use them as chemical markers for identifying different
      sources of PAH pollutants in the studied region. The total content of these16
      PAHs ranged from 399.616 up to 67,631.779 ng/g wet weight. The data show that
      these values are considered to be alarmingly high enough to cause lethal toxicity
      effect by accumulation. All studied aquatic species samples are characterized by
      relatively high concentrations of the six-membered ring PAHs. The origin of PAHs
      in the collected samples is either petrogenic, biogenic, or mixed petrogenic and
      biogenic. 

PMID- 24092255
TI  - Development of a robust chromatographic method for the detection of chlorophenols
      in cork oak forest soils.
AB  - A major concern for the cork and wine industry is 'cork taint' which is
      associated with chloroanisoles, the microbial degradation metabolites of
      chlorophenols. The use of chlorophenolic compounds as pesticides within cork
      forests was prohibited in 1993 in the European Union (EU) following the
      introduction of industry guidance. However, cork produced outside the EU is still
      thought to be affected and simple, robust methods for chlorophenol analysis are
      required for wider environmental assessment by industry and local environmental
      regulators. Soil samples were collected from three common-use forests in Tunisia
      and from one privately owned forest in Sardinia, providing examples of varied
      management practice and degree of human intervention. These provided challenge
      samples for the optimisation of a HPLC-UV detection method. It produced
      recoveries consistently >75% against a soil CRM (ERM-CC008) for
      pentachlorophenol. The optimised method, with ultraviolet (diode array) detection
      is able to separate and quantify 16 different chlorophenols at field
      concentrations greater than the limits of detection ranging from 6.5 to 191.3
      MUg/kg (dry weight). Application to a range of field samples demonstrated the
      absence of widespread contamination in forest soils at sites sampled in Sardinia
      and Tunisia.

PMID- 24092256
TI  - Understanding the need of ventricular pressure for the estimation of diastolic
      biomarkers.
AB  - The diastolic function (i.e., blood filling) of the left ventricle (LV) is
      determined by its capacity for relaxation, or the decay in residual active
      tension (AT) generated during systole, and its constitutive material properties,
      or myocardial stiffness. The clinical determination of these two factors
      (diastolic residual AT and stiffness) is thus essential for assessing LV
      diastolic function. To quantify these two factors, in our previous work, a novel
      model-based parameter estimation approach was proposed and successfully applied
      to multiple cases using clinically acquired motion and invasively measured
      ventricular pressure data. However, the need to invasively acquire LV pressure
      limits the wide application of this approach. In this study, we address this
      issue by analyzing the feasibility of using two kinds of non-invasively available
      pressure measurements for the purpose of inverse mechanical parameter estimation.
      The prescription of pressure based on a generic pressure-volume (P-V)
      relationship reported in literature is first evaluated in a set of 18 clinical
      cases (10 healthy and 8 diseased), finding reasonable results for stiffness but
      not for residual active tension. We then investigate the use of non-invasive
      pressure measures, now available through imaging techniques and limited by
      unknown or biased offset values. Specifically, three sets of physiologically
      realistic synthetic data with three levels of diastolic residual active tension
      (i.e., impaired relaxation capability) are designed to quantify the percentage
      error in the parameter estimation against the possible pressure offsets within
      the physiological limits. Maximum errors are quantified as 11 % for the magnitude
      of stiffness and 22 % for AT, with averaged 0.17 kPa error in pressure
      measurement offset using the state-of-the-art non-invasive pressure estimation
      method. The main cause for these errors is the limited temporal resolution of
      clinical imaging data currently available. These results demonstrate the
      potential feasibility of the estimation diastolic biomarkers with non-invasive
      assessment of pressure through medical imaging data.

PMID- 24092257
TI  - Simulation of long-term fatigue damage in bioprosthetic heart valves: effects of
      leaflet and stent elastic properties.
AB  - One of the major failure modes of bioprosthetic heart valves (BHVs) is
      noncalcific structural deterioration due to fatigue of the tissue leaflets; yet,
      the mechanisms of fatigue are not well understood. BHV durability is primarily
      assessed based on visual inspection of the leaflets following accelerated wear
      testing. In this study, we developed a computational framework to simulate BHV
      leaflet fatigue, which is both efficient and quantitative, making it an
      attractive alternative to traditional accelerated wear testing. We utilize a
      phenomenological soft tissue fatigue damage model developed previously to
      describe the stress softening and permanent set of the glutaraldehyde-treated
      bovine pericardium leaflets in BHVs subjected to cyclic loading. A parametric
      study was conducted to determine the effects of altered leaflet and stent elastic
      properties on the fatigue of the leaflets. The simulation results show that
      heterogeneity of the leaflet elastic properties, poor leaflet coaptation, and
      little stent-tip deflection may accelerate leaflet fatigue, which agrees with
      clinical findings. Therefore, the developed framework may be an invaluable tool
      for evaluating leaflet durability in new tissue valve designs, including
      traditional BHVs as well as new transcatheter valves. 

PMID- 24092258
TI  - A C(3v)-symmetrical tribenzotriquinacene-based threefold N-heterocyclic carbene.
      Coordination to rhodium(I) and stereoelectronic properties.
AB  - A novel tribenzotriquinacene-based tris-NHC has been obtained and coordinated to
      rhodium. The new ligand displays a unique rigid C3v symmetry. The electrochemical
      analysis of the tri-rhodium complex reveals that the three metals are essentially
      disconnected. 

PMID- 24092259
TI  - Venous thromboembolism prophylaxis in hematopoietic stem cell transplantation
      patients: an international web-based survey of healthcare providers.

PMID- 24092260
TI  - Clinicopathologic characteristics and overall survival in patients with bladder
      cancer involving the gastrointestinal tract.
AB  - Involvement of the gastrointestinal (GI) tract by bladder cancer is rare and
      documented in only a few case reports with no prognostic information available.
      The aim of this study was to clinicopathologically characterize patients with
      pathologically proven bladder cancer in the GI tract. We reviewed pathology
      reports from cystectomy patients at our institution from 2006 to 2011,
      identifying those with GI involvement at or after cystectomy. Overall survival
      (OS) was analyzed using Kaplan-Meier curves and Cox proportional hazard
      regression models. Twelve patients had surgical pathology specimens with GI
      involvement (anus, rectum, colon, and small bowel) at (n = 11) or within 4 months
      (n = 1) of cystectomy. These patients were noted to be pathologically staged
      inconsistently. GI involvement was a negative predictor of survival, with a 1.5
      year OS of 25 versus 62 % without GI involvement (P < 0.001), similar to our pT4
      patients (OS 26 %). In node-negative patients, there was a significantly worse
      1.5-year OS with GI involvement compared to those without tumor in the GI tract
      (P = 0.005). We provide the first case series of patients with bladder cancer in
      the GI tract. GI involvement is a strong negative predictor of survival and
      behaves comparable to pT4 patients. However, we recommend that pathologists
      adhere to the current pT staging guidelines, in which GI involvement is not a
      criterion, until further research is conducted illustrating if and how it should
      be incorporated.

PMID- 24092261
TI  - Monoclonal antibody HBME-1 reacts with a minor subset of B cells with villous
      surface and can be useful in the diagnosis of hairy cell leukemia and other
      indolent lymphoproliferations of villous B lymphocytes.
AB  - The Hector Battifora mesothelial epitope-1 (HBME-1) monoclonal antibody has been
      generated against human mesothelioma cells and recognizes a biochemically unknown
      membrane epitope. We have accidentally found that the HBME-1 reacts with
      scattered lymphocytes showing villous surface in hyperplastic lymphoid tissue. To
      evaluate its reactivity pattern, we have performed a consecutive
      immunohistochemical study in nonneoplastic bone marrow and lymphoid samples (n =
      40), as well as in malignant lymphoproliferations (n = 427), including hairy cell
      leukemia (HCL) (n = 72), HCL variant (HCL-v) (n = 13), splenic diffuse red pulp
      small B cell lymphoma (SDRPL) (n = 8), splenic B cell marginal zone lymphoma
      (SMZL) (n = 59), and splenic B cell lymphoma/leukemia, not further classifiable
      on bone marrow morphology (SBCL) (n = 37) cases. The staining pattern of HBME-1
      was compared to DBA.44. HBME-1(+) villous lymphocytes were constantly detected in
      low number in nonneoplastic lymphoid tissues. With multicolor immunofluorescence
      staining, HBME-1(+) lymphocytes showed a CD20(+)/CD79a(+)/IgM(+) B cell
      phenotype. In B cell lymphoproliferations of villous lymphocytes, HBME-1
      reactivity was demonstrated in 96 % of HCL, 39 % of HCL-v, 50 % of SDRPL, 12 % of
      SMZL, and 19 % of SBCL cases. Nodal and extranodal marginal zone lymphoma cases
      were positive in 12 % of the cases. A small minority (4 %) of the other B cell
      lymphomas and no T cell lymphoma revealed tumor cell reactivity with HBME-1. In
      conclusion, our study has established that HBME-1 reacts with a minor subset of B
      lymphocytes and a small proportion of B cell lymphomas, which has not been
      described previously. We suggest that HBME-1 can be a useful marker in the
      diagnosis of HCL and other indolent lymphoproliferations of villous B
      lymphocytes.

PMID- 24092262
TI  - Structure of GrlR-GrlA complex that prevents GrlA activation of virulence genes.
AB  - The locus of enterocyte effacement (LEE) is essential for virulence of
      enterohaemorrhagic Escherichia coli (EHEC) and enteropathogenic E. coli (EPEC).
      The 41 genes of the LEE encode type III secretion system proteins and three
      associated regulators: Ler, GrlA and GrlR. Ler is a positive regulator for most
      of the LEE operons, including grlRA. GrlA controls the expression of ler, ehxCABD
      and flhDC operons. GrlR binds to GrlA and suppresses its function. Here we report
      the crystal structure of GrlR-GrlADelta (aa 1-106) complex (2:1) and its
      functional characterization. We show that GrlR interacts with the Helix-Turn
      Helix motif of GrlA. Moreover, GrlA binds to the promoter DNA fragments of ler,
      ehxCABD and flhDC, and GrlR outcompetes with these promoter DNA sequences for the
      Helix-Turn-Helix motif of GrlA. These findings provide mechanistic insight into a
      regulatory module for the virulence of EPEC and EHEC, two important pathogens
      that cause devastating diseases. 

PMID- 24092263
TI  - Nuclear medicine 2013: from status quo to status go.

PMID- 24092264
TI  - Is nano too big?

PMID- 24092265
TI  - Treatment monitoring with (18)F-FDG PET/CT in a patient with peritoneal
      tuberculosis.

PMID- 24092266
TI  - Prediction of thermodynamically reversible hydrogen storage reactions utilizing
      Ca-M(M = Li, Na, K)-B-H systems: a first-principles study.
AB  - Calcium borohydride is a potential candidate for onboard hydrogen storage because
      it has a high gravimetric capacity (11.5 wt.%) and a high volumetric hydrogen
      content (~130 kg m(-3)). Unfortunately, calcium borohydride suffers from the
      drawback of having very strongly bound hydrogen. In this study, Ca(BH4)2 was
      predicted to form a destabilized system when it was mixed with LiBH4, NaBH4, or
      KBH4. The release of hydrogen from Ca(BH4)2 was predicted to proceed via two
      competing reaction pathways (leading to CaB6 and CaH2 or CaB12H12 and CaH2) that
      were found to have almost equal free energies. Using a set of recently developed
      theoretical methods derived from first principles, we predicted five new hydrogen
      storage reactions that are among the most attractive of those presently known.
      These combine high gravimetric densities (>6.0 wt.% H2) with have low enthalpies
      [approximately 35 kJ/(mol(-1) H2)] and are thermodynamically reversible at low
      pressure within the target window for onboard storage that is actively being
      considered for hydrogen storage applications. Thus, the first-principles
      theoretical design of new materials for energy storage in future research appears
      to be possible.

PMID- 24092267
TI  - Stability and properties of the two-dimensional hexagonal boron nitride monolayer
      functionalized by hydroxyl (OH) radicals: a theoretical study.
AB  - Motivated by the great advance in graphene hydroxide--a versatile material with
      various applications--we performed density functional theory (DFT) calculations
      to study the functionalization of the two-dimensional hexagonal boron nitride (h
      BN) sheet with hydroxyl (OH) radicals, which has been achieved experimentally
      recently. Particular attention was paid to searching for the most favorable
      site(s) for the adsorbed OH radicals on a h-BN sheet and addressing the roles of
      OH radical coverage on the stability and properties of functionalized h-BN sheet.
      The results indicate that, for an individual OH radica, the most stable
      configuration is that it is adsorbed on the B site of the h-BN surface with an
      adsorption energy of -0.88 eV and a magnetic moment of 1.00 MU(B). Upon
      adsorption of more than one OH radical on a h-BN sheet, however, these adsorbates
      prefer to adsorb in pairs on the B and its nearest N atoms from both sides of h
      BN sheet without magnetic moment. An energy diagram of the average adsorption
      energy of OH radicals on h-BN sheet as a function of its coverage indicates that
      when the OH radical coverage reaches to 60 %, the functionalized h-BN sheet is
      the most stable among all studied configurations. More importantly, this
      configuration exhibits good thermal and dynamical stability at room temperature.
      Owing to the introduction of certain impurity levels, the band gap of h-BN sheet
      gradually decreases with increasing OH coverage, thereby enhancing its electrical
      conductivity.

PMID- 24092268
TI  - Acute chest pain evaluation: is there too much stress on the system?

PMID- 24092269
TI  - Does hybrid imaging have a role in cardiac risk evaluation of the pre-renal
      transplant patient?

PMID- 24092270
TI  - The relationship between ischemia-induced left ventricular dysfunction, coronary
      flow reserve, and coronary steal on regadenoson stress-gated (82)Rb PET
      myocardial perfusion imaging.
AB  - BACKGROUND: Gated rubidium-82 ((82)Rb) positron emission tomography (PET) imaging
      studies are acquired both at rest and during pharmacologic stress. Stress-induced
      ischemic left ventricular dysfunction (LVD) can produce a significant decrease in
      left ventricular ejection fraction (LVEF) from rest to stress. We determined the
      prevalence on PET of stress LVD with reduced ejection fraction (EF) and its
      association with absolute global and regional coronary flow reserve (CFR), and
      with relative perfusion defect summed difference score (SDS). METHODS AND
      RESULTS: We studied 205 patients with known or suspected coronary disease (120 M,
      75 F, age 69 +/- 13 years) who had clinically indicated rest/regadenoson stress
      (82)Rb PET/CT studies. Data were acquired in dynamic gated list mode. Global and
      17-segment regional CFR values were computed from first-pass flow data using a 2
      compartment model and factor analysis applied to auto-generated time-activity
      curves. Rest and stress LVEF and SDS were quantified from gated equilibrium
      myocardial perfusion tomograms using Emory Cardiac Toolbox software. LVD was
      defined as a change in LVEF of <=-5% from rest to stress. A subgroup of 109
      patients also had coronary angiography. Stress LVD developed in 32 patients
      (16%), with mean EF change of -10 +/- 5%, vs +6 +/- 7% for patients without LVD
      (P < .0001). EF was similar at rest in patients with and without stress LVD (57
      +/- 18% vs 56 +/- 16%, P = .63), but lower during stress for patients with LVD
      (47 +/- 20% vs 61 +/- 16%, P = .0001). CFR was significantly lower in patients
      with LVD (1.61 +/- 0.67 vs 2.21 +/- 1.03, Wilcoxon P = .002), and correlated
      significantly with change in EF (r = 0.35, P < .0001), but not with SDS (r = 
      0.13, P = .07). The single variable most strongly associated with high risk of
      CAD (i.e., left main stenosis >=50%, LAD % stenosis >=70%, and/or 3-vessel
      disease) was stress EF (chi(2) = 17.3, P < .0001). There was a higher prevalence
      of patients with territorial CFR values <=1.0, consistent with coronary steal, in
      the LVD group than in the non-LVD group (39% vs 12%, P = .001). CONCLUSIONS: LVD
      developed in 16% of patients undergoing (82)Rb PET myocardial perfusion imaging,
      and was associated with multivessel coronary artery disease. There was a
      significant relationship between LVD and coronary blood flow during stress, with
      LVD corresponding to a low CFR. Territorial CFR <=1.0 was more common in patients
      with LVD than those without, suggesting that coronary steal is an important
      pathophysiologic mechanism contributing to pharmacologic stress-induced LVD.

PMID- 24092271
TI  - Molecular imaging in cardiovascular disease: Which methods, which diseases?
AB  - Techniques for in vivo assessment of disease-related molecular changes are being
      developed for all forms of non-invasive cardiovascular imaging. The ability to
      evaluate tissue molecular or cellular phenotype in patients has the potential to
      not only improve diagnostic capabilities but to enhance clinical care either by
      detecting disease at an earlier stage when it is more amenable to therapy, or by
      guiding most appropriate therapies. These new techniques also can be used in
      research programs in order to characterize pathophysiology and as a surrogate
      endpoint for therapeutic efficacy. The most common approach for molecular imaging
      involves the creation of novel-targeted contrast agents that are designed so that
      their kinetic properties are different in disease tissues. The main focus of this
      review is not to describe all the different molecular imaging approaches that
      have been developed, but rather to describe the status of the field and highlight
      some of the clinical and research applications that molecular imaging will likely
      provide meaningful benefit. Specific target areas include assessment of
      atherosclerotic disease, tissue ischemia, and ventricular and vascular
      remodeling. 

PMID- 24092272
TI  - Prognostic value of left ventricular mechanical dyssynchrony by phase analysis in
      patients with non-ischemic cardiomyopathy with ejection fraction 35-50% and QRS <
      150 ms.
AB  - BACKGROUND: Left ventricular mechanical dyssynchrony (LVMD) by phase analysis of
      gated single-photon emission computed tomography (SPECT) myocardial perfusion
      imaging (MPI) is a useful tool for predicting response to cardiac
      resynchronization therapy and has prognostic value. While most of the studies
      were done on patients with ischemic cardiomyopathy or those with LV ejection
      fraction (EF) < 35%, there are little data on the prognostic value of LVMD in
      patients with non-ischemic cardiomyopathy (NICM), particularly those with mildly
      decreased systolic function and narrow or intermediate QRS duration. METHODS AND
      RESULTS: From the stress SPECT-MPI database at Cleveland Clinic, we identified
      324 consecutive patients (mean age 62 +/- 13 years, 62% male, 36% diabetics) with
      NICM, LVEF 35-50% (median [Q1,Q3] 45 [41,49]), and QRS < 150 ms (13% with QRS 120
      149 ms). LVMD was determined from gated stress images and expressed as phase
      standard deviation (SD) and histogram BW (% R-R cycle). For easier graphical
      illustration, patients were divided into tertiles of LVMD. All-cause death was
      the primary endpoint and determined using the Social Security Death Index. Cox
      proportional hazard model was performed to determine the independent predictive
      value of LVMD, and next Cox models for incremental value. After a mean follow-up
      time of 1,689 days, 86 (26.5%) of patients died. These patients were older, had
      more diabetes, more use of diuretics, with wider QRS duration, and with a trend
      for higher phase SD and BW. After adjusting for age, hypertension, diabetes,
      aspirin, beta-blockers, diuretics, QRS, and EF, phase SD was an independent
      predictor of all-cause mortality with hazard ratio [95% CI] 1.97 [1.06,3.66] for
      the highest tertile, and added incremental prognostic value (P = .025). Similar
      findings were obtained using histogram BW. CONCLUSION: In patients with NICM, EF
      35-50%, and QRS < 150 ms, increased LVMD on peak stress SPECT was an independent
      predictor of all-cause mortality. The utility and applicability of such findings
      in clinical practice need further evaluation in larger and prospective studies.

PMID- 24092273
TI  - Warranty period of normal stress myocardial perfusion imaging in diabetic
      patients: a propensity score analysis.
AB  - BACKGROUND: We evaluated the relationship between diabetes and temporal
      characteristics of cardiac risk at long-term follow-up in a propensity score
      matched cohort of diabetic and non-diabetic patients with normal stress
      myocardial perfusion single-photon emission computed tomography (MPS). METHODS
      AND RESULTS: We studied 828 consecutive patients with suspected or known coronary
      artery disease and normal perfusion at stress MPS. To account for differences in
      baseline characteristics between diabetics and non-diabetics, we created a
      propensity score-matched cohort considering clinical variables and stress type.
      After matching, clinical characteristics were comparable in 260 diabetic and 260
      non-diabetic patients. All patients were followed for at least 1 year (median 53
      months). End-point events were cardiac death or nonfatal myocardial infarction.
      At Cox analysis, diabetes (hazard ratio 3.9, P < .01) and post-stress left
      ventricular ejection fraction (LVEF) <=45% (hazard ratio 4.1, P < .01) were
      independent predictors of events. At parametric analysis, non-diabetic patients
      with post-stress LVEF >45% remained at low risk for the entire length of follow
      up, while the highest probability of events and the major risk acceleration was
      observed in patients with diabetes and post-stress LVEF <=45%. CONCLUSIONS: After
      a normal stress MPS, diabetic patients are at higher risk for cardiac events than
      non-diabetic subjects also after balancing clinical characteristics and stress
      type by propensity score analysis. The warranty period of a normal stress MPS
      varies according to diabetic status and post-stress LVEF.

PMID- 24092274
TI  - Surgical technique: Hemilaminectomy and unilateral lateral mass fixation for
      cervical ossification of the posterior longitudinal ligament.

PMID- 24092275
TI  - Solidago, orthosiphon, birch and cranberry extracts can decrease microbial
      colonization and biofilm development in indwelling urinary catheter: a
      microbiologic and ultrastructural pilot study.
AB  - PURPOSE: Plants extracts are used in urology to manage urinary tract infections.
      We aimed to evaluate the efficacy of a preparation with solidago, orthosiphon,
      birch and cranberry extracts (CISTIMEV PLUS((r))) in reducing microbial
      colonization and biofilm development in patients with indwelling urinary
      catheters. METHODS: All consecutive outpatients attending our department between
      January and June 2010 for the substitution of indwelling catheters were
      considered for this single-blinded, randomized and controlled pilot study to test
      superiority of the preventative management (CISTIMEV PLUS((r)), 1 tablet daily
      for 30 days) in respect to no treatment. A sample size of 10-40 participants per
      group was considered adequate. All patients underwent urine culture the same day
      of the catheter substitution and were then randomized into test group (n = 48)
      and control group (n = 35). Ultrastructural analysis was also performed. After 30
      days, the catheter was replaced and the analysis repeated. The primary outcome
      was the rate of positive urinary culture at the end of the entire study period.
      RESULTS: Ten patients abandoned the study. At 30 days, according to per-protocol
      analysis, the groups statistically differed regarding the rate of positive urine
      cultures: test group 10/43 and control group 16/30 (p = 0.013) (-30.1 % [95 % CI 
      51.94 to -8.21]). The most common isolated bacteria were Escherichia coli and
      Enterococcus faecalis. CONCLUSIONS: The use of solidago, orthosiphon, birch and
      cranberry extracts resulted in a significant reduction of microbial colonization
      in patients with indwelling urinary catheters. Larger clinical trials are needed
      to demonstrate that the effects here reported are sufficient to reduce
      symptomatic catheter-associated urinary tract infections.

PMID- 24092277
TI  - Investigation of milk proteins binding to the oral mucosa.
AB  - High protein dairy beverages are considered to be mouth drying. The drying
      sensation may be due to the product protein content; however the mechanism of
      this mouth drying is uncertain. This study investigated the potential adhesion of
      milk proteins to porcine oral mucosa in vitro. Purified casein and beta
      lactoglobulin were fluorescently labelled, placed on porcine oral mucosal tissues
      and their resistance to wash out with simulated saliva was monitored using
      fluorescence microscopy. Casein was found to be more adhesive to porcine mucosa
      than beta-lactoglobulin. Some investigation into the reason for this difference
      in mucoadhesion was conducted by thiol-content analysis, rheology and zeta
      potential measurements. The higher viscosity of casein solution and smaller zeta
      potential is believed to be responsible for its better retention on mucosal
      surfaces. These findings suggest that casein and whey protein are both capable of
      binding and eliciting mouth drying in high protein dairy beverages. 

PMID- 24092276
TI  - Organ-sparing surgery is the treatment of choice in benign testicular tumors.
AB  - PURPOSE: Ablation of the testis has been the reference standard for malignant and
      benign testicular tumors in the past. Nowadays, an organ-sparing surgery (OSS)
      can be attempted in special cases. Removal of a testis for a benign lesion should
      be avoided. In this retrospective survey, we analyze the results and long-term
      follow-up of OSS in benign testicular tumors. METHODS: Charts of all patients
      that underwent OSS because of a benign testicular tumor between 1999 and 2011 at
      our department were searched and the data from patients were collected. Before
      surgery, all patients underwent ultrasound (US) and complete staging. Surgery was
      performed under US or palpation guidance. Frozen-section examination of the tumor
      and tumor bed biopsies was obtained. All patients underwent postoperative follow
      up. We retrospectively reviewed surgical technique, histology, epidemiology, and
      outcome in all patients. RESULTS: In the study period, 40 benign testicular
      tumors were surgically removed in 37 consecutive patients. Definitive histology
      did not report of any malignant histopathologic features in all patients. All
      patients are free of disease after a mean follow-up of 63 months (range 10-120).
      During this period, two patients developed a second leydig cell tumor (LCT) on
      the contralateral side; another patient had a second LCT within the same
      testicle, but on the opposite pole. All patients underwent a subsequent organ
      sparing tumor resection. CONCLUSIONS: An overtreatment for benign testicular
      tumors should be avoided. Our initial results indicate that OSS in benign tumors
      is a safe, feasible treatment for patients.

PMID- 24092278
TI  - Establishing a familial basis for papillary thyroid carcinoma using the Utah
      Population Database.
AB  - IMPORTANCE: Determining if relatives of patients diagnosed as having papillary
      thyroid carcinoma (PTC) are at increased risk of developing the same cancer--and
      if so, which relatives and to what degree--would help identify those who require
      closer clinical attention. This could lead to earlier cancer detection and
      improved prognoses. OBJECTIVE: To define the familial risk of PTC using a unique
      population research database. DESIGN, SETTING, PARTICIPANTS: Retrospective review
      at a tertiary care facility using the Utah Population Database, which is linked
      to medical records and the Utah Cancer Registry, from 1966 through 2011. The
      study population comprised 4460 patients diagnosed as having PTC in Utah between
      1966 and 2011 and their first- through fifth-degree relatives and spouses. These
      patients were compared 5:1 with matched, population-based controls. MAIN OUTCOMES
      AND MEASURES: Statistically significant increased risk of PTC in any first-
      through fifth-degree relatives or spouses of patients diagnosed as having this
      cancer. RESULTS: First-, second-, and third-degree relatives of PTC probands had
      a significant increased risk of developing this cancer compared with population
      controls. First-degree relatives of probands were at a 5.4-fold increased risk (P
      < 10(-15)) of being diagnosed as having this cancer themselves. Second- and third
      degree relatives had a 2.2-fold (P < 10(-11)) and 1.8-fold increased risk (P <
      10(-8)), respectively. Siblings of probands were at highest risk (odd ratio, 6.8;
      P < 10(-15)). There was no significant increased risk observed in spouses of
      probands. CONCLUSIONS AND RELEVANCE: In the largest population study to date, a
      high risk of PTC is confirmed in first-degree relatives. Furthermore, significant
      increased risk extends to second- and third-degree relatives but not to spouses
      of probands. Translational studies are needed to better define the genetic
      predisposition to familial papillary thyroid cancer and for the development and
      implementation of optimal screening approaches.

PMID- 24092279
TI  - Effects of resonant excitation, pulse duration and intensity on photoelectron
      imaging of a dianion.
AB  - The photoelectron imaging of the indigo carmine dianion is used to demonstrate
      the effects of resonance excitation, pulse duration and pulse intensity on the
      photoelectron spectra and angular distributions of a dianion. Excitation of the
      S1 state leads to an aligned distribution of excited state dianions. The
      photoelectron angular distribution following subsequent photodetachment within a
      femtosecond laser pulse is primarily determined by the repulsive Coulomb barrier.
      Extending the timescale for photodetachment to nanoseconds leads to dramatic
      changes in both the spectral and angular distributions. These observations are
      explained in terms of statistical detachment of electrons, either from the
      monoanion, or from the ground state of the dianion following a number of photon
      cycles through the S1 <- S0 transition. At high intensity, new electron emission
      channels open up, leading to emission below the repulsive Coulomb barrier. This
      has been assigned to strong-field induced detachment and the effect of an
      electric field on the Coulomb barrier is discussed in terms of the photoelectron
      spectra and angular distributions. 

PMID- 24092285
TI  - Neither too much nor too little movement.

PMID- 24092287
TI  - Tremor syndromes.
AB  - PURPOSE OF REVIEW: The purpose of this review is to explain a practical clinical
      approach to the diagnosis and management of tremor. RECENT FINDINGS: A number of
      rare but important causes of tremor have been delineated, which means that
      attention to detail in clinical assessment of patients with tremor is even more
      important. SUMMARY: Tremors are best divided into those occurring mainly at rest,
      mainly on posture, and mainly during action. This basic division leads directly
      to differential diagnosis and effective treatment.

PMID- 24092286
TI  - Parkinsonian syndromes.
AB  - PURPOSE OF REVIEW: The different parkinsonian conditions can be challenging to
      separate clinically. This review highlights the important clinical features that
      guide the diagnosis of Parkinson disease (PD), progressive supranuclear palsy
      (PSP), multiple system atrophy (MSA), and corticobasal degeneration (CBD).
      Strategies for treatment and disease management are also discussed. RECENT
      FINDINGS: Over the past decade there has been an increasing recognition of the
      broad clinical presentations of the neurodegenerative forms of parkinsonism.
      Nonmotor symptoms in these diseases, including psychiatric, cognitive, autonomic,
      and gastrointestinal dysfunction, appear to have a major impact on quality of
      life and disability. PSP and CBD are now considered pathologic diagnoses, with
      several different and varied clinical phenotypes, that overlap and share features
      with PD and frontotemporal dementia syndromes. PD is distinguished by its
      excellent response to dopaminergic medications that is maintained over many
      years, in contrast to the response seen in patients with MSA and PSP. New
      diagnostic criteria have been proposed for CBD. No new therapeutic interventions
      have emerged for PSP, MSA, or CBD. Infusional therapies and deep brain
      stimulation surgery are established therapies for advanced PD. SUMMARY: The
      "parkinsonian syndromes" encompass a number of nosologic entities that are
      grouped together on the basis of their shared clinical features but are separated
      on the basis of their different pathologies. Overall, the consideration of
      clinical signs, mode of disease onset, and nature of disease progression are all
      important to make a timely and definitive diagnosis.

PMID- 24092288
TI  - Dystonia.
AB  - PURPOSE OF REVIEW: The purpose of this review is to provide an update on the
      classification, phenomenology, pathophysiology, and treatment of dystonia. RECENT
      FINDINGS: A revised definition based on the main phenomenologic features of
      dystonia has recently been developed in an expert consensus approach.
      Classification is based on two main axes: clinical features and etiology.
      Currently, genes have been reported for 14 types of monogenic isolated and
      combined dystonia. Isolated dystonia (with dystonic tremor) can be caused by
      mutations in TOR1A (DYT1), TUBB4 (DYT4), THAP1 (DYT6), PRKRA (DYT16), CIZ1
      (DYT23), ANO3 (DYT24), and GNAL (DYT25). Combined dystonias (with parkinsonism or
      myoclonus) are further subdivided into persistent (GCHI [DYT5], SGCE [DYT11], and
      ATP1A3 [DYT12], with TAF1 most likely but not yet proven to be linked to DYT3)
      and paroxysmal (PNKD [DYT8], PRRT2 [DYT10], and SLC2A1 [DYT18]). Recent insights
      from neurophysiologic studies identified functional abnormalities in two networks
      in dystonia: the basal ganglia-sensorimotor network and, more recently, the
      cerebellothalamocortical pathway. Besides the well-known lack of inhibition at
      different CNS levels, dystonia is specifically characterized by maladaptive
      plasticity in the sensorimotor cortex and loss of cortical surround inhibition.
      The exact role (modulatory or compensatory) of the cerebellar-cortical pathways
      still has to be further elucidated. In addition to botulinum toxin for focal
      forms, deep brain stimulation of the globus pallidus internus is increasingly
      recognized as an effective treatment for generalized and segmental dystonia.
      SUMMARY: The revised classification and identification of new genes for different
      forms of dystonia, including adult-onset segmental dystonia, enable an improved
      diagnostic approach. Recent pathophysiologic insights have fundamentally
      contributed to a better understanding of the disease mechanisms and impact on
      treatment, such as functional neurosurgery and nonpharmacologic treatment
      options.

PMID- 24092289
TI  - Chorea.
AB  - PURPOSE OF REVIEW: Chorea is a relatively common movement disorder that can be
      caused by a large variety of structural, autoimmune, neurodegenerative,
      pharmacologic, and metabolic disturbances of basal ganglia function. The
      diagnosis is rarely indicated by the phenotypic appearance of chorea and can be
      challenging, with many patients remaining undiagnosed. This review highlights
      salient features that may be observed or elicited in the case of a person with
      chorea, which may provide an indication of the diagnosis. RECENT FINDINGS: Recent
      advances in genetics have identified genes for new disorders and expanded the
      phenotype of recognized conditions. New therapies include tetrabenazine, a
      presynaptic dopamine depleter, and deep brain stimulation. SUMMARY: Clues to
      diagnosis may be found in the patient's family or medical history, on neurologic
      examination, or upon laboratory testing and neuroimaging. While most therapies at
      present are supportive, correct diagnosis is essential for appropriate genetic
      counseling and ultimately for future molecular therapies.

PMID- 24092290
TI  - Myoclonus.
AB  - PURPOSE OF REVIEW: Myoclonus remains a challenging movement phenotype to
      characterize, evaluate, and treat. A systematic assessment of the temporal
      sequence, phenomenology, and distribution of movements can assist in the rational
      approach to diagnosis and management. RECENT FINDINGS: Cortical forms of
      myoclonus are increasingly recognized as primarily cerebellar disorders. A
      syndrome of orthostatic myoclonus has been recognized by electrophysiology in
      patients with neurodegenerative disorders, mainly in Alzheimer disease,
      accounting for impairments in gait and balance previously mischaracterized as
      normal pressure hydrocephalus or orthostatic tremor. Tyrosine hydroxylase
      deficiency and Silver-Russell syndrome (uniparental disomy of chromosome 7) have
      been established as two novel causes of the myoclonus-dystonia syndrome.
      Mutations in the glycine receptor (GlyR) alpha1-subunit gene (GLRA1) explain the
      major expression of hyperekplexia, an inherited excessive startle disorder,
      butnewly identified mutations in GlyR beta-subunit (GLRB) and glycine transporter
      2 (GlyT2) genes (SLC6A5) account for "minor" forms of this disorder manifested as
      excessive startle and hypnic jerks. The entity previously known as palatal
      myoclonus has been reclassified as palatal tremor in recognition of its clinical
      and electromyographic features and no longer enters the differential diagnosis of
      myoclonic disorders. Increasing documentation of psychogenic features in patients
      previously characterized as having propriospinal myoclonus has cast doubts on the
      existence of this distinctive disorder. SUMMARY: Myoclonus can be a prominent
      manifestation of a wide range of disorders. Electrophysiologic testing aids in
      distinguishing myoclonus from other mimics and classifying them according to
      cortical, subcortical, or spinal origin, which assists the choice of treatment.
      Despite the lack of randomized clinical trials, levetiracetam appears most
      effective in patients with cortical myoclonus, whereas clonazepam remains the
      only first-line therapeutic option in subcortical and spinal myoclonus.

PMID- 24092291
TI  - Tic disorders.
AB  - PURPOSE OF REVIEW: Primary tic disorders are complex, multifactorial disorders in
      which tics are accompanied by other sensory features and an array of comorbid
      behavioral disorders. Secondary tics are proportionally much less frequent, but
      their etiology is diverse. This review aims to guide clinicians in the
      recognition of the phenomenology, pathophysiology, and treatment of these
      disorders. RECENT FINDINGS: Advances include greater phenomenologic insights,
      particularly of nonmotor (sensory) features; increased knowledge of disease
      mechanisms, particularly coming from neuropsychological, functional imaging,
      pathologic, and animal model studies; growing evidence on the efficacy of alpha-2
      agonists and the newer generation of dopamine-modulating agents; and recent
      strides in the evaluation of cognitive-behavioral therapy and deep brain
      stimulation surgery. SUMMARY: The correct diagnostic approach to tic disorders
      requires accurate historical gathering, a thorough neurologic examination, and
      detailed definition of the patient's psychopathologic profile. Treatment should
      always begin with individualized psychoeducational strategies. Although
      pharmacologic treatments remain beneficial for most patients, cognitive
      behavioral treatments have thus far shown promising efficacy. Deep brain
      stimulation surgery should still be limited to adult patients refractory to
      pharmacotherapy and cognitive-behavioral therapy.

PMID- 24092292
TI  - Cerebellar and afferent ataxias.
AB  - PURPOSE OF REVIEW: Ataxia is the predominant manifestation of many acquired and
      inherited neurologic disorders affecting the cerebellum, its connections, and the
      afferent proprioceptive pathways. This article reviews the phenomenology and
      etiologies of cerebellar and afferent ataxias and provides indications for a
      rational approach to diagnosis and management. RECENT FINDINGS: The
      pathophysiology of ataxia is being progressively understood and linked to the
      functional organization of the cerebellum. The impact of cerebellar diseases on
      different neurologic functions has been better defined and shown not to be
      limited to loss of motor coordination. The role of autoimmunity is increasingly
      recognized as a cause of sporadic cases of ataxia. Large collaborative studies of
      long duration are providing crucial information on the clinical spectrum and
      natural history of both sporadic ataxias (such as the cerebellar form of multiple
      system atrophy) and inherited ataxias. New dominant and recessive ataxia genes
      have been identified. On the therapeutic front, progress mostly concerns the
      development of treatments for Friedreich ataxia. SUMMARY: Ataxia is the clinical
      manifestation of a wide range of disorders. In addition to accurate clinical
      assessment, MRI plays a major role in the diagnostic workup, allowing us to
      distinguish degenerative conditions from those due to other types of structural
      damage to the cerebellar or proprioceptive systems. Diagnostic algorithms based
      on clinical features, imaging, and neurophysiologic and biochemical parameters
      can be used to guide genetic testing for hereditary ataxias, the diagnosis of
      which is likely to be greatly improved by the introduction of new-generation DNA
      sequencing approaches. Some rare forms of ataxia can be treated, so their
      diagnosis should not be missed. Proven symptomatic treatments for ataxia are
      still lacking, but intensive physical therapy appears to be helpful.

PMID- 24092293
TI  - Gait disorders.
AB  - PURPOSE OF REVIEW: This article provides insight and reviews useful tools for the
      clinical assessment, understanding, and management of neurologic gait disorders.
      RECENT FINDINGS: In recent years, our understanding of the physiology of human
      walking has steadily increased. The recognition of gait as a complex, "higher
      order" form of motor behavior with prominent influence of mental processes has
      been an important new insight, and the clinical implications of gait disorders
      are increasingly being recognized. Better classification schemes, the
      redefinition of established entities (eg, senile gait), and new insights from
      research on degenerative disorders primarily affecting gait (eg, primary
      progressive freezing of gait) have become available. SUMMARY: Gait disorders are
      directly correlated with poor quality of life and increased mortality. Because
      gait is very sensitive to any insult to the nervous system, its assessment should
      be carried out carefully in routine clinical practice. Disorders of locomotion
      are easily discernible to the naked eye. However, when examining gait, clinicians
      should bear in mind that the clinical phenotype is the net result of changes
      induced by the disease itself plus any compensations adopted by the patient to
      improve stability. This review presents a clinically oriented approach to gait
      disorders based on the dominant phenomenology and underlying pathophysiology,
      which are tightly connected. The authors conclude by proposing a practical
      management approach.

PMID- 24092295
TI  - The ethics of refusing a request for off-label deep brain stimulation currently
      in clinical trial.
AB  - Physicians must ensure that patients understand that the principal aim of
      research is to increase generalizable knowledge. However, patients may hope for
      individual benefit as a secondary goal of participation. Highly motivated
      patients may request treatment off label if trial enrollment has ended, leading
      to ethical dilemmas for clinicians. This case uses early deep brain stimulation
      (DBS) as an example for exploring the ethically relevant questions related to the
      off-label use of medical devices. 

PMID- 24092294
TI  - Psychogenic movement disorders.
AB  - PURPOSE OF REVIEW: This review describes the main clinical features of
      psychogenic (functional) movement disorders and reports recent advances in
      diagnosis, pathophysiology, and treatment. RECENT FINDINGS: The terminology and
      definition of patients with psychogenic movement disorders remain subjects of
      controversy; the term "functional" has been used more frequently in the
      literature in recent years regarding the neurobiological substrate underpinning
      these disorders. Correct diagnosis of psychogenic movement disorders should rely
      not on the exclusion of organic disorders or the sole presence of psychological
      factors but on the observation or elicitation of clinical features related to the
      specific movement disorder (ie, a positive or inclusionary rather than
      exclusionary diagnosis). Sudden onset, spontaneous remissions, and variability
      over time or during clinical examination are useful "red flags" suggestive of a
      psychogenic movement disorder. Imaging studies have demonstrated impaired
      connectivity between limbic and motor areas involved in movement programming and
      hypoactivity of a brain region that compares expected data with actual sensory
      data occurring during voluntary movement. Treatment of psychogenic movement
      disorders begins with ensuring the patient's acceptance of the diagnosis during
      the initial debriefing and includes nonpharmacologic (cognitive-behavioral
      therapy, physiotherapy) and pharmacologic options. SUMMARY: Psychogenic movement
      disorders represent a challenging disorder for neurologists to diagnose and
      treat. Recent advances have increased understanding of the neurobiological
      mechanism of psychogenic movement disorders. Treatment with cognitive strategies
      and physical rehabilitation can benefit some patients. As short duration of
      disease correlates with better prognosis, early diagnosis and initiation of
      treatment are critical.

PMID- 24092296
TI  - Video recording in movement disorders: practical issues.
AB  - Video recording can provide a valuable and unique record of the physical
      examinations of patients with a movement disorder, capturing nuances of movement
      and supplementing the written medical record. In addition, video is an
      indispensable tool for education and research in movement disorders. Digital file
      recording and storage has largely replaced analog tape recording, increasing the
      ease of editing and storing video records. Practical issues to consider include
      hardware and software configurations, video format, the security and longevity of
      file storage, patient consent, and video protocols. 

PMID- 24092297
TI  - Coding for the use of botulinum toxin for movement disorders.

PMID- 24092304
TI  - REBEn(r): herald of the technical-scientific production and of the social
      political project of the Brazilian nursing.

PMID- 24092305
TI  - [85 years of ABEn(r) and 80 of REBEn(r) promoting the scientific and professional
      development of Brazilian nursing].
AB  - This is an academic effort to rescue fragments of the construction process of an
      entity pioneering the representativeness of the Brazilian nursing - the Brazilian
      Nursing Association (ABEn), who completed 85 years of existence and created the
      first scientific journal of nursing, Nursing Annals, currently the Brazilian
      Nursing Journal, which celebrated 80 years in 2012. The contribution of ABEn for
      the scientific and professional development of nursing in the country is
      approached with analytical and critical humility and very timid perspective,
      since it was based more on information from secondary sources than on primary
      ones, according to an overview about what happen from 1926 to 2011. The
      subjectivity and selectivity of facts led us to highlight some instances of power
      over others, to highlight points of the development of Brazilian nursing as a
      discipline, profession and work field. 

PMID- 24092306
TI  - [About the professional identity in nursing: punctual reconsiderations in
      philosophical vision].
AB  - This paper is a contribution to the 80th years of the Brazilian Nursing Journal,
      official journal of the Brazilian Nurses Association, first nominated Nursing
      Annals and created in May 1932. At that time, the issues were focused as
      proposals to assure exchange communication between the Professional Class -the
      National Brazilian Graduate Nurses Association - and the associates, including
      all the people. In this way, the associate leaders were impelled through
      professional advances allied to the knowledge production regarding to the
      Professional Know/Knowledge, the practice assistance and education. The approach
      is through discussion and analytical appreciation about professional identity
      with punctual reconsiderations in philosophical vision. Instead of researching
      parameters the author prefers a pragmatic style around examples of three
      situations-problem as succeeded in the practical assistance, so that they could
      be critically appreciated alike fundamental basis to the nurses' art and enough
      to assure the definition of the professional profile in the historical-evolutive
      trajectory - with beginning in the nightingalean modernity and the proper assumed
      parsonian concepts - as such they are observed in the Brazilian Nursing
      literature. Without through off the subject, only the specific questions are
      submitted. Key words: Nursing; Professional Identity; Nurse Art. 

PMID- 24092307
TI  - Confronting moral distress in nursing: recognizing nurses as moral agents.
AB  - The concept of moral distress has brought forth a substantively different way of
      understanding some of the difficulties confronted by nurses in their practice.
      This concept highlights that nurses' distress can be an indication of nurses'
      conscientious moral engagement with their professional practice that has
      confronted practices or an environment that impedes them from acting according to
      their own ethical standards. Moral distress can be an indicator of problems in
      nurses' practice environments. This concept is described and related to moral
      agency in nursing practice. Selected research on moral distress is reviewed,
      followed by a discussion of recommendations for addressing this problem. 

PMID- 24092308
TI  - [Necessary changes for advancing nursing as caring science].
AB  - The article aimed to reflect upon the challenges involved in strengthening
      Nursing as a caring science. It is founded on the sociological theory, connecting
      three approaches: the historical-dialectic materialism perspective about the
      working process in health care and nursing; the sociology of professions from a
      critical perspective; and the philosophy of science. The discussion is organized
      considering the aspects of Nursing as a discipline, work and health care
      profession. It sustains that knowledge production should be driven both by the
      purpose of Nursing work which is providing care to human beings with health needs
      and to advocate for the indispensable work conditions to a safe and responsible
      practice. It concludes that to strengthening Nursing it is necessary to produce
      knowledge to support nursing care and the political actions defending safe work
      conditions, the universal right to health as well safe and high quality care. 

PMID- 24092309
TI  - [The classical and the emerging: challenges in the production, dissemination and
      use of nursing knowledge].
AB  - This is a reflection about the paradigms of science and the contemporary
      challenges deriving from knowledge production, dissemination and use. The
      challenges are addressed with regard to research on nursing care, resources and
      political strategies in the area to overcome them. The arguments rest on nursing
      as a practical discipline and on the triad teaching-care-research, focused on
      users' demands, with a view to the promotion of health and wellbeing, within a
      care paradigm. Articulating the science models, expanding human, material and
      financial resources, investing in professional master's programs, in the
      expansion of academic graduate programs and in the formation of cooperation
      networks are some of the challenges and strategies indicated for the area to face
      the struggles in the hegemonic area of health, science and technology, so as to
      continue in the system. 

PMID- 24092310
TI  - [Knowledge in nursing: from the area representation to the Nursing Advisory
      Committee at CNPq].
AB  - The aim was to describe aspects of the nursing evolution in the National Council
      for Scientific and Technological Development (Conselho Nacional de
      Desenvolvimento Cientifico e Tecnologico - CNPq), focusing on the organizational
      structure and positions of the Area Representation and the advances in nursing
      knowledge. This is an experience report, accompanied by reflections and attitudes
      towards science, technology and innovation of Brazilian nursing and the creation
      of the Nursing Advisory Committee at the CNPq, in 2006. This paper is intended
      for the special issue of the Brazilian Nursing Journal (Revista Brasileira de
      Enfermagem), a prominent scientific nursing journal of nursing, in the
      celebration of its 80 years of existence. Brazilian nursing records scientific
      qualification advances in the preparation of its researchers, marking a new era
      in the consolidation and recognition of the discipline and profession. 

PMID- 24092311
TI  - [Classification of the CNPq areas of knowledge and the nursing field:
      possibilities and limits].
AB  - Knowledge areas have been discussed by Science and Technology managers and
      administrators and by the scientific community searching for tools to support
      data systematization, mainly for management and administrative activities. The
      main table in use by CNPq is admittedly outdated and requires revision or
      reclassification. The aim of this article is to contribute to the current debate
      based on previous results from participation in a table review study performed in
      the 1990 s and on research results in the area of knowledge organization and
      representation in the context of Information Science. It presents a proposal to
      reformulate the Nursing Knowledge Area and some reflections about the
      possibilities of this ongoing process.

PMID- 24092312
TI  - [Discussions on research lines in the National Nursing Research Seminars, 1979
      2011].
AB  - The article aimed to recover historical and synthesis of discussions within the
      National Seminar on Nursing Research (SENPE) about research lines, materializing
      in this context, the construction of nursing knowledge. This is a documentary
      research, whose sources were the Annals of sixteen SENPE, conducted from 1979 to
      2011. It was observed that the discussion on the research lines was a constant
      concern in those Seminars, although with different gradations, from its genesis
      to the present time. The scenario configures itself with the inclusion of adverse
      consequences of the quantitative production and dissemination of studies without
      necessarily articulated them with a praxis purpose. The concerns externalized in
      the trajectory analyzed inaugurate the search for praxis in nursing to contribute
      to the discussion of the research from the perspective of the political nature of
      the construction, dissemination and evaluation of knowledge, from the
      understanding of the contradictions inherent in this process. 

PMID- 24092313
TI  - [The research and the ethical dilemmas of nursing work].
AB  - This paper is a reflection on research and the ethical dilemmas of nursing work,
      with the primary objective of providing subsidies to help thinking about care,
      according to professional practice in the field of education, research, and
      particularly of assistance. We rely on authors who deal about ethics, labor and
      human condition, finding a link between this knowledge and nursing's doing in its
      daily practice. We conclude that given the reality of health, amid so many
      adversities with which we are faced in day-to-day practice, whether in teaching,
      research or nursing care, to think and to act ethically is a structuring
      condition, which humanizes and ennobles the profession giving meaning to the
      actions of its professionals. 

PMID- 24092314
TI  - [The strict sense nursing postgraduation in Brazil: advances and perspectives].
AB  - Nursing is a specific field of knowledge and social practice that has been
      consolidated and strengthened as science. In Brazil, it has been developed due to
      the increase and qualification of strict sense post-graduate programs. This study
      aims to present a historical review of the strict sense post-graduate nursing
      courses in Brazil and to reflect on their evolution, progress, challenges and
      future perspectives. It explores the creation of strict sense post-graduate
      courses, highlighting the movement to build a culture of academic and
      professional post-graduation in nursing. The historical path of their
      consolidation, expansion, conquest of excellence and international visibility
      over four decades, and the challenges and future perspectives are showed. It is
      found that the post-graduate programs in the field has contributed to the
      advancement and consolidation of scientific, technological knowledge and
      innovation in nursing and health care, having as philosophy the respect for
      diversity and the free exchange of ideas, the improvement of quality of life and
      health, and the effectiveness of citizenship. 

PMID- 24092315
TI  - [Lessons learned with the work as a Network in Nursing and Midwifery].
AB  - The Global Network of WHO Collaborating Centres for Nursing and Midwifery
      Development is an independent, international, non-profit organization, with 44
      Collaborating Centres. Among its members there are internationally recognized
      nursing and midwifery leaders, what emphasizes the unique meaning of this group.
      Based on its history, this article describes how the work as a network can
      transform isolated actions with specific results in convergent and synergic
      actions with expanded results and impact in academia, services and the political
      arena. 

PMID- 24092316
TI  - [A decade of National Curriculum Guidelines for Graduation in Nursing: advances
      and challenges].
AB  - The Curriculum Guidelines of the Undergraduate Nursing are references to the
      strengthening of the changes in training of professionals critics and committed
      to health. Seeking to identify these changes, this study aimed to analyze the
      progress and challenges of a decade of these Guidelines. This is a documentary
      research, in which it was analyzed the Law of Guidelines and Bases of National
      Education, the CNE / CES Resolution n o 03/2001, and the Brazilian intellectual
      production on the theme in the decade of 2001 to 2011. This production was sought
      in scientific journals, through the data bases BDENF, SciELO and LILACS. The
      analysis was anchored on the methodological framework of the dialectic which
      provided the study of the subject in its dynamism, contradictions and all of its
      inclusion in public policy. The results showed improvements in the strengthening
      of change in nursing education, in line with the policies of education and
      health. 

PMID- 24092317
TI  - [Overview of Nursing Graduation courses in Brazil in the National Curriculum
      Guidelines decade].
AB  - The study aims to build a general overview of the Nursing Graduation Programs in
      Brazil, in the decade of the National Curriculum Guidelines for Nursing
      Graduation, period 2001-2011. This is an exploratory, descriptive study, based on
      data from the e-MEC, Higher Education Census, ENADE. The results evidenced: the
      privatization of the Nursing Graduation Programs, the oversupply of courses and
      places day and night; sharp expansion of the number of vacancies for distance
      learning, not meeting the minimum quality criteria evaluated by ENADE, among
      other respects. It is recommended that strategies for the regulation of the
      expansion already installed must be defined, in addition to the revision of
      indicators drawn from the INEP Single Form, to meet the necessities of nursing,
      as an specific area, particularly with regard to: the number of vacancies,
      integration with the local and regional health system and the SUS, education in
      health care, teaching practical activities, working arrangements and experience
      of the faculty of the course. It is recommended, though, the immediate
      intervention of the MEC in the poles of Distance Education, suspending the
      training of nurses in that modality of education. 

PMID- 24092318
TI  - [Nursing knowledge production: transposition and repercussions on the graduation
      teaching].
AB  - The research aimed to analyze the production of knowledge in nursing at a public
      university, in order to evaluate the impact of that production during the Nursing
      Graduation. An exploratory and descriptive research has been done in two stages.
      The first one consisted of gathering the reports of researches executed by the
      teachers who coordinated them from 2000 to 2009. As a result of this stage, it
      was mapped the type of studies performed, the themes and the theoretical and
      methodological references most utilized. During the second stage we studied the
      current pedagogical project used in the Graduation course, and crossed the data
      with the previously, to create a dimension to some of the transpositions and
      applications of the knowledge produced by the researches to the Nursing
      Graduation course. We concluded that, in different ways, not only the application
      of the studies has been occurring but also the transposition of ideals that cross
      through the research groups to which they belong, being able to bring change to
      nursing education. 

PMID- 24092319
TI  - [Science, public health and nursing: highlighting the gender and generation
      categories in the episteme of praxis].
AB  - This essay aims to show the relevance of sociological categories gender and
      generation that underlie the phenomenon of nursing in public health, the episteme
      of praxis. We understand praxis as the foundation of the historical and dialectic
      materialism, demonstrating its importance in the process of construction of
      knowledge in public health nursing. The sociological categories of gender and
      generation were chosen in this paper because it has the privilege to better
      illuminate certain phenomena that have been the subject of scientific concern,
      such as violence against women, children and the elderly, in all its
      vulnerabilities. The dialectical method was adopted, with an emphasis on the
      secondary laws of "essence and phenomena" and "reality and possibility". Finally,
      given that the choice of the approach to the object, as well as the instruments
      for intervention towards a purpose in the process of scientific knowledge is the
      choice of the knowing subject, the ethics was related to praxis. 

PMID- 24092320
TI  - [Contribution of standardized languages for knowledge production, clinical
      reasoning and clinical nursing practice].
AB  - The standardized language systems are important tools for dealing with the
      increasing complexity of nursing care. In this article the authors present the
      main benefits that the use of these systems provide for the required clinical
      reasoning in nursing care, the construction and organization of knowledge of the
      discipline, and for the clinical practice of nursing. The potential contributions
      of the standardized language systems in these fields stem from the fact that
      these systems provide a formal structure for supporting clinical reasoning,
      organizing knowledge and nursing experience. 

PMID- 24092321
TI  - [The ICNP(r) terminology and the Brazilian ICNP(r) Centre participation on its
      development and dissemination].
AB  - This paper aims to describe (1) the evolution of the International Classification
      for Nursing Practice (ICNP(r) ), since the International Council of Nurses (ICN)
      assumed, in 1989, the task of developing a classification of the elements of
      professional practice (nursing diagnoses, interventions and outcomes) with an
      international ambit; (2) the ICNP(r) Programme and its structural components,
      which fit together to conform the ICNP(r) terminology life cycle; (3) the Centres
      for ICNP(r) Research and Development, accredited by ICN; (4) finally, the
      Brazilian Center's contribution for research, development and dissemination of
      the ICNP(r) terminology. The ICNP(r) is constantly evolving and much has been
      achieved in nearly twenty-five years of its development. The ICNP(r) Centres have
      played a key role in the development, dissemination and use of the terminology in
      different fields of professional practice - teaching, clinical practice, research
      and management of nursing care. 

PMID- 24092322
TI  - [Nurses of large public hospitals in Rio de Janeiro: socio demographic and work
      related characteristics].
AB  - The study aimed at analyzing socio-demographic and working characteristics of
      nurses from public hospitals. It was carried out a cross-sectional study,
      involving 3.229 nurses from the eighteen largest public hospitals of the city of
      Rio de Janeiro. It was observed a feminine predominance (87.3%), with mean age of
      39.9 +/- 10 years. Around 7% referred having master or doctorate degree, 58.5%
      got their degree from public institutions and 24.5% used to work at the health
      sector before becoming nurses. Half the group has thought of abandoning their
      career, and almost a quarter is unsatisfied with their profession. Around 10%
      searched for a job outside nursing area in the previous month and 30% searched
      for a job in the same working area. Night work, engagement in more than one job
      and long professional work hours were more frequently found among men. The study
      has pointed challengeable aspects of nurses' profession. Results can subsidize
      support strategies to improve the working conditions in public hospitals due to
      their comprehensiveness.

PMID- 24092323
TI  - [Primary health care essential attributes and the family health strategy].
AB  - The essential attributes of Primary Health Care are attention at first contact,
      longitudinality, completeness and coordination, and the derived attributes are
      family and community orientation and cultural competence. This paper discusses
      the presence of such attributes in Family Health Strategy, a political and
      governmental proposal to change the health care model in the context of the
      Unified Health System in Brazil. 

PMID- 24092324
TI  - [The ABEn and the professional memory preserving: the Brazilian Nursing Memory
      Centre implantation].
AB  - This is a historical-social study, which aimed to analyze and argue the on the
      importance of the Brazilian Nursing Memory Centre for preservation and publicity
      of the professional memory. As data sources it was used the documentary
      Associacao Brasileira de Enfermagem: 1926-1976, and the Project of Implantation
      and the Technical Report of the Memory Centre's Documentary and Phonic
      Collection, both filed in the referred Centre. The data, collected in June 2013,
      were subjected to external and intern criticism, aiming to its validation. The
      analysis occurred concurrently with data collection and was made based on
      knowledge about the topic, supported by Bourdieu's concept of habitus. It was
      observed that, since 1926, the directions of the Brazilian Nursing Association
      contributed for the Memory Centre implantation, by means of the importance
      attributed to the preservation of the memory. It was concluded that the memory
      enshrined in the collection constitutes material and symbolic goods for the
      Brazilian nursing to be transmitted through the historiography derived from it. 

PMID- 24092325
TI  - [The psychiatric nursing, ABEn and the Scientific Department of Psychiatric and
      Mental Health Nursing: progress and challenges].
AB  - This study contextualizes the Psychiatric Nursing and Mental Health in Brazil,
      considering the major historic, political and social factors that influence
      nursing care in this area. Reflections pointed to changes in the paradigm of
      psychosocial care considering the legal aspects that regulate the actions,
      progress and challenges experienced in the practice of Psychiatric Nursing in
      healthcare settings as well as in nursing education. It is essential to train
      professionals to work in management and assistance in perspective and
      interdisciplinary care network. The achievements for this specialty rush on a
      scientific critical and organized politically and who knows answer the reality of
      professionals. In this view, the Scientific Department of Psychiatric Nursing and
      Mental Health, created by the Brazilian Association of Nursing was installed as a
      strategy to bring together and consolidate the work of experts, aiming to achieve
      the excellence of the Specialized Care in Psychiatry and Mental Health. 

PMID- 24092326
TI  - [Scientific Department of Gerontological Nursing of the Brazilian Nursing
      Association].
AB  - This paper aimed to consider the creation of the Scientific Department of
      Gerontological Nursing within the Brazilian Nursing Association, considering the
      context of population ageing, and the development and consolidation of this
      specialty in the country. In the reflexive process, it was possible to rely on
      the historical analysis of the revised literature and authors' reports. The
      results showed the movement of nurses, in recent decades, to the production of
      knowledge, as well as their incorporation by the entity, and the commitment of
      its members to achieve the goals proposed to the Scientific Department of
      Gerontological Nursing. It is concluded that its creation represents a milestone
      to the scientific and political organization of the nursing professionals who
      seek to qualify themselves for an autonomous and competent care of the elderly
      and their families. 

PMID- 24092327
TI  - Automatic medical X-ray image classification using annotation.
AB  - The demand for automatically classification of medical X-ray images is rising
      faster than ever. In this paper, an approach is presented to gain high accuracy
      rate for those classes of medical database with high ratio of intraclass
      variability and interclass similarities. The classification framework was
      constructed via annotation using the following three techniques: annotation by
      binary classification, annotation by probabilistic latent semantic analysis, and
      annotation using top similar images. Next, final annotation was constructed by
      applying ranking similarity on annotated keywords made by each technique. The
      final annotation keywords were then divided into three levels according to the
      body region, specific bone structure in body region as well as imaging direction.
      Different weights were given to each level of the keywords; they are then used to
      calculate the weightage for each category of medical images based on their ground
      truth annotation. The weightage computed from the generated annotation of query
      image was compared with the weightage of each category of medical images, and
      then the query image would be assigned to the category with closest weightage to
      the query image. The average accuracy rate reported is 87.5 %. 

PMID- 24092328
TI  - DNase hypersensitive sites and association with multiple sclerosis.
AB  - Genome-wide association studies (GWASs) have shown that approximately 60 genetic
      variants influence the risk of developing multiple sclerosis (MS). Our aim was to
      identify the cell types in which these variants are active. We used available
      data on MS-associated single nucleotide polymorphisms (SNPs) and
      deoxyribonuclease I hypersensitive sites (DHSs) from 112 different cell types.
      Genomic intervals were tested for overlap using the Genomic Hyperbrowser. The
      expression profile of the genes located nearby MS-associated SNPs was assessed
      using the software GRAIL (Gene Relationships Across Implicated Loci). Genomic
      regions associated with MS were significantly enriched for a number of immune
      DHSs and in particular T helper (Th) 1, Th17, CD8+ cytotoxic T cells, CD19+ B
      cells and CD56+ natural killer (NK) cells (enrichment = 2.34, 2.19, 2.27, 2.05
      and 1.95, respectively; P < 0.0001 for all of them). Similar results were
      obtained when genomic regions with suggestive association with MS and additional
      immune-mediated traits were investigated. Several new candidate MS-associated
      genes located within regions of suggestive association were identified by GRAIL
      (CARD11, FCRL2, CHST12, SYK, TCF7, SOCS1, NFKBIZ and NPAS1). Genetic data
      indicate that Th1, Th17, cytotoxic T, B and NK cells play a prominent role in the
      etiology of MS. Regions with confirmed and suggestive association have a similar
      immunological profile, indicating that many SNPs truly influencing the risk of MS
      actually fail to reach genome-wide significance. Finally, similar cell types are
      involved in the etiology of other immune-mediated diseases. 

PMID- 24092329
TI  - DISC1 complexes with TRAK1 and Miro1 to modulate anterograde axonal mitochondrial
      trafficking.
AB  - Disrupted-In-Schizophrenia 1 (DISC1) is a candidate risk factor for
      schizophrenia, bipolar disorder and severe recurrent depression. Here, we
      demonstrate that DISC1 associates robustly with trafficking-protein-Kinesin
      binding-1 which is, in turn, known to interact with the outer mitochondrial
      membrane proteins Miro1/2, linking mitochondria to the kinesin motor for
      microtubule-based subcellular trafficking. DISC1 also associates with Miro1 and
      is thus a component of functional mitochondrial transport complexes. Consistent
      with these observations, in neuronal axons DISC1 promotes specifically
      anterograde mitochondrial transport. DISC1 thus participates directly in
      mitochondrial trafficking, which is essential for neural development and
      neurotransmission. Any factor affecting mitochondrial DISC1 function is hence
      likely to have deleterious consequences for the brain, potentially contributing
      to increased risk of psychiatric illness. Intriguingly, therefore, a rare
      putatively causal human DISC1 sequence variant, 37W, impairs the ability of DISC1
      to promote anterograde mitochondrial transport. This is likely related to a
      number of mitochondrial abnormalities induced by expression of DISC1-37W, which
      redistributes mitochondrial DISC1 and enhances kinesin mitochondrial association,
      while also altering protein interactions within the mitochondrial transport
      complex. 

PMID- 24092330
TI  - The role of the mitochondrial ribosome in human disease: searching for mutations
      in 12S mitochondrial rRNA with high disruptive potential.
AB  - Mutations of mitochondrial DNA are linked to many human diseases. Despite the
      identification of a large number of variants in the mitochondrially encoded rRNA
      (mt-rRNA) genes, the evidence supporting their pathogenicity is, at best,
      circumstantial. Establishing the pathogenicity of these variations is of major
      diagnostic importance. Here, we aim to estimate the disruptive effect of mt-rRNA
      variations on the function of the mitochondrial ribosome. In the absence of
      direct biochemical methods to study the effect of mt-rRNA variations, we relied
      on the universal conservation of the rRNA fold to infer their disruptive
      potential. Our method, named heterologous inferential analysis or HIA, combines
      conservational information with functional and structural data obtained from
      heterologous ribosomal sources. Thus, HIA's predictive power is superior to the
      traditional reliance on simple conservation indexes. By using HIA, we have been
      able to evaluate the disruptive potential for a subset of uncharacterized 12S mt
      rRNA variations. Our analysis revealed the existence of variations in the rRNA
      component of the human mitoribosome with different degrees of disruptive power.
      In cases where sufficient information regarding the genetic and pathological
      manifestation of the mitochondrial phenotype is available, HIA data can be used
      to predict the pathogenicity of mt-rRNA mutations. In other cases, HIA analysis
      will allow the prioritization of variants for additional investigation.
      Eventually, HIA-inspired analysis of potentially pathogenic mt-rRNA variations,
      in the context of a scoring system specifically designed for these variants,
      could lead to a powerful diagnostic tool. 

PMID- 24092332
TI  - Characterization of carboxylesterase in skin mucus of Cirrhinus mrigala and its
      assessment as biomarker of organophosphate exposure.
AB  - Presence of carboxylesterase (CbE) activity in the skin mucus of Cirrhinus
      mrigala was investigated. CbE activity in skin mucus showed higher substrate
      preference for alpha-naphthyl acetate over p-nitrophenyl acetate. Four CbE
      isozymes-CbE-1, CbE-2, CbE-3, and CbE-4 were observed in skin mucus during
      zymography. The isozyme CbE-4 was characterized as typical serine esterase,
      whereas CbE-1, CbE-2, and CbE-3 were identified as sulphhydryl group-dependent
      serine esterases. In vitro treatment of skin mucus with the organophosphorus
      insecticide, Nuvan((r)) showed strong inhibition of CbE activity. In vivo
      exposure of the fish to sublethal test concentrations (5 and 15 mg/l) of the
      insecticide also revealed significant inhibition of CbE activity in mucus. After
      the cessation of exposure, CbE activity recovered to its control level during the
      recovery periods. Thus, CbE activity in skin mucus could be considered a
      biomarker of the organophosphorus insecticide exposure to fish and a useful tool
      in monitoring environmental toxicity. 

PMID- 24092333
TI  - Enhancing cell nucleus accumulation and DNA cleavage activity of anti-cancer drug
      via graphene quantum dots.
AB  - Graphene quantum dots (GQDs) maintain the intrinsic layered structural motif of
      graphene but with smaller lateral size and abundant periphery carboxylic groups,
      and are more compatible with biological system, thus are promising nanomaterials
      for therapeutic applications. Here we show that GQDs have a superb ability in
      drug delivery and anti-cancer activity boost without any pre-modification due to
      their unique structural properties. They could efficiently deliver doxorubicin
      (DOX) to the nucleus through DOX/GQD conjugates, because the conjugates assume
      different cellular and nuclear internalization pathways comparing to free DOX.
      Also, the conjugates could enhance DNA cleavage activity of DOX markedly. This
      enhancement combining with efficient nuclear delivery improved cytotoxicity of
      DOX dramatically. Furthermore, the DOX/GQD conjugates could also increase the
      nuclear uptake and cytotoxicity of DOX to drug-resistant cancer cells indicating
      that the conjugates may be capable to increase chemotherapy efficacy of anti
      cancer drugs that are suboptimal due to the drug resistance.

PMID- 24092334
TI  - Definition and classification of pulmonary hypertension.
AB  - Pulmonary hypertension is defined as an increase of mean pulmonary arterial
      pressure >=25 mmHg at rest as assessed by right heart catheterization. According
      to different combinations of values of pulmonary wedge pressure, pulmonary
      vascular resistance and cardiac output, a hemodynamic classification of pulmonary
      hypertension has been proposed. Of major importance is the pulmonary wedge
      pressure which allows to distinguish pre-capillary (pulmonary wedge pressure <=15
      mmHg) and post-capillary (pulmonary wedge pressure >15 mmHg) pulmonary
      hypertension. Pre-capillary pulmonary hypertension includes the clinical groups 1
      (pulmonary arterial hypertension), 3 (pulmonary hypertension due to lung diseases
      and/or hypoxia), 4 (chronic thrombo-embolic pulmonary hypertension) and 5
      (pulmonary hypertension with unclear and/or multifactorial mechanisms). Post
      capillary pulmonary hypertension corresponds to the clinical group 2 (pulmonary
      hypertension due to left heart diseases). 

PMID- 24092331
TI  - Regulation of the unfolded protein response by microRNAs.
AB  - The unfolded protein response (UPR) is an adaptive response to the stress that is
      caused by an accumulation of misfolded proteins in the lumen of the endoplasmic
      reticulum (ER). It is an important component of cellular homeostasis. During ER
      stress, the UPR increases the protein-folding capacity of the endoplasmic
      reticulum to relieve the stress. Failure to recover leads to apoptosis. Specific
      cellular mechanisms are required for the cellular recovery phase after UPR
      activation. Using bioinformatics tools, we identified a number of microRNAs that
      are predicted to decrease the mRNA expression levels for a number of critical
      components of the UPR. In this review, we discuss the potential role of microRNAs
      as key regulators of this pathway and describe how microRNAs may play an
      essential role in turning off the UPR after the stress has subsided. 

PMID- 24092335
TI  - Pulmonary hypertension: pathophysiology and signaling pathways.
AB  - Pulmonary hypertension (PH) is characterized by pathological changes to cell
      signaling pathways within the alveolar-pulmonary arteriole-right ventricular axis
      that results in increases in pulmonary vascular resistance and, ultimately, the
      development of right ventricular (RV) dysfunction. Cornerstone histopathological
      features of the PH vasculopathy include intimal thickening, concentric
      hypertrophy, and perivascular fibrosis of distal pulmonary arterioles. The
      presence of plexogenic lesions is pathognomonic of pulmonary arterial
      hypertension (PAH); when present, this severe form of remodeling is associated
      with subtotal obliteration of the blood vessel lumen. The extent of RV remodeling
      in PH correlates with clinical symptom severity and portends a poor outcome.
      Currently available PH-specific pharmacotherapies that aim to improve symptom
      burden by targeting pulmonary vasodilatory/vasoconstrictor cell signaling
      pathways do not fully reverse pulmonary vascular remodeling and, thus, are
      largely unsuccessful at maintaining normal cardiopulmonary hemodynamics long
      term. Thus, determining the molecular mechanisms that are responsible for
      pulmonary vascular remodeling in PH is of great potential therapeutic value,
      particularly pathways that promote apoptosis-resistant cellular proliferation,
      disrupt normal cellular bioenergetics to alter cell function, and/or modulate
      severely abnormal responses to pulmonary vascular injury. This chapter reviews
      current insights into PH pathophysiology and disease mechanisms, and discusses
      novel cell signaling pathways that implicate microRNAs and mitochondrial
      dysfunction in the development of the PH phenotype. 

PMID- 24092336
TI  - Pulmonary hypertension: pathology.
AB  - Pulmonary hypertension (PH) is a life-threatening and often fatal disease,
      characterized by elevated pulmonary vascular resistance and secondary right
      ventricular failure. Since etiologies of PH are multiple and its pathogenesis is
      complex, histology from lungs of patients with PH may help us to determine
      different etiological factors of the disease. The degree of involvement of
      various cell types and structures within the lung tissue represents an important
      indicator of the pathophysiologal process. So even if the role for pathologists
      in routine management of PH is limited, lessons can be learned from morphology.
      The present chapter outlines the current understanding of this disease from the
      pathologist's point of view. 

PMID- 24092338
TI  - Rodent models of group 1 pulmonary hypertension.
AB  - World Health Organization category 1 pulmonary hypertension (PH) is a
      heterogeneous syndrome in which PH originates in the small pulmonary arteries and
      is therefore also referred to as pulmonary arterial hypertension (PAH). Common
      pathophysiologic features include endothelial dysfunction, excessive
      proliferation and impaired apoptosis of vascular cells, and mitochondrial
      fragmentation. The proliferation/apoptosis imbalance relates in part to
      activation of the transcription factors hypoxia-inducible factor-1alpha (HIF
      1alpha) and nuclear factor of activated T-cells (NFAT) and apoptosis repressors,
      such as survivin. Perivascular inflammation, disruption of adventitial connective
      tissue, and a glycolytic metabolic shift in vascular cells and right ventricular
      myocytes also occur in PAH. There are important genetic and epigenetic
      predispositions to PAH. This review assesses the fidelity of existing animal
      models to human PAH. No single model can perfectly recapitulate the many diverse
      forms of PH in Category 1; however, acceptable models exist. PAH induced by
      monocrotaline and chronic hypoxia plus SU-5416 (CH+SU) in rats display
      endothelial dysfunction, proliferation/apoptosis imbalance, and develop the
      glycolytic metabolic profile of human PAH. Histologically, CH+SU best conforms to
      PAH in that it develops complex vascular lesions, including plexiform lesions.
      However, the monocrotaline model can be induced to manifest complex vascular
      lesions and does manifest the tendency of PAH patients to die of right
      ventricular (RV) failure. Murine models offer greater molecular certainty than
      rat models but rarely develop significant PH, have less right ventricular
      hypertrophy (RVH) and pulmonary artery (PA) remodeling, and are harder to image
      and catheterize. The use of high fidelity catheterization and advanced imaging
      (microPET-CT, high frequency echocardiography, high field strength MRI) and
      functional testing (treadmill) permit accurate phenotyping of experimental models
      of PAH. Preclinical trial design is an important aspect of testing experimental
      PAH therapies. The use of multiple complementary models with adequate sample size
      and trial duration and appropriate endpoints are required for preclinical
      assessment of experimental PAH therapies. 

PMID- 24092337
TI  - Pulmonary hypertension: biomarkers.
AB  - Physicians look to biomarkers to inform the management of pulmonary hypertension
      (PH) at all stages, from assessing susceptibility through screening, diagnosis,
      and risk stratification to drug selection and monitoring. PH is a heterogeneous
      disorder and currently there are no accepted blood biomarkers specific to any
      manifestation of the condition. Brain natriuretic peptide and its N-terminal
      peptide have been most widely studied. Other candidate prognostic biomarkers in
      patients with pulmonary arterial hypertension (PAH) include growth and
      differentiation factor-15, red cell distribution width, uric acid, creatinine,
      inflammatory markers such as interleukin-6, angiopoietins, and microRNAs.
      Combining the measurement of biomarkers reflecting different components of the
      pathology with other modalities may enable better molecular characterisation of
      PH subtypes and permit improved targeting of therapeutic strategies and disease
      monitoring. 

PMID- 24092339
TI  - General supportive care.
AB  - In addition to PAH-specific therapies proven to be effective in achieving a
      better outcome and/or symptomatic improvement, the care of patients with
      pulmonary arterial hypertension (PAH) requires a complex strategy that includes
      general pharmacological and non-pharmacological measures. This chapter will
      detail the general supportive measures beneficial for PAH patients as adjuvant
      treatment to targeted therapies. 

PMID- 24092340
TI  - Calcium-channel blockers in pulmonary arterial hypertension.
AB  - Voltage-activated calcium channels are a family of membrane proteins that provide
      the major influx pathway for calcium in many different types of cells. Calcium
      channel blockers inhibit the calcium influx into vascular cells leading to
      relaxation of smooth muscle cells and vasodilatation. Vasoconstriction of small
      pulmonary arteries is recognized as a component of the pathogenesis of pulmonary
      arterial hypertension and treatment with calcium-channel blockers appears to be
      rational in this setting. No randomized controlled trial has been performed to
      demonstrate the beneficial effects of calcium-channel blockers in the treatment
      of patients with pulmonary arterial hypertension. However, uncontrolled studies
      have suggested that long-term administration of high-dose calcium antagonists
      dramatically improves survival in a small subset of patients who respond acutely
      to those drugs, compared with unresponsive patients. The initial response to an
      acute vasodilator test with inhaled nitric oxide or intravenous prostacyclin or
      adenosine accurately identifies patients with pulmonary arterial hypertension who
      are likely to respond to long-term treatment with calcium-channel blockers. 

PMID- 24092341
TI  - Prostacyclins.
AB  - Prostacyclins have a favourable pharmacological profile for treatment of
      pulmonary hypertension as they possess vasodilative, antiproliferative,
      antiaggregatory, and anti-inflammatory properties that may compensate the main
      pathologic changes in the small pulmonary arteries. In severe pulmonary
      hypertension these vessels show a deficit in the endogenous prostacyclin
      secretion. The therapeutic potential of prostacyclin for pulmonary hypertension
      has been known since 30 years, and since nearly 20 years prostacyclin has been
      approved for idiopathic PAH. There are intravenous, subcutaneous, and inhaled
      approaches of different substances who share many but not all pharmacologic
      properties. However, none of these approaches are easy and free of adverse
      effects. Long-term experience and careful decision-making are instrumental to
      achieve favourable clinical long-term results. 

PMID- 24092342
TI  - Endothelin receptor antagonists.
AB  - Three pathways have been identified in the pathogenesis of pulmonary arterial
      hypertension (PAH): the endothelin (ET), nitric oxide (NO) and prostacyclin
      pathways. These pathways represent the targets of approved PAH therapies and
      their discovery has facilitated significant progress in the understanding and
      treatment of PAH. The ET system is well established as a key player in the
      pathophysiology of PAH, with deleterious effects mediated by both the ETA and ETB
      receptors. Endothelin receptor antagonists (ERAs) are an important part of PAH
      therapy, with two ERAs currently approved for the treatment of PAH and a novel
      ERA that has recently been investigated in a Phase III clinical trial. This
      chapter describes the role of ET in the pathogenesis of PAH, reviews experimental
      data and examines the clinical status of ERAs in PAH treatment. 

PMID- 24092343
TI  - Phosphodiesterase-5 inhibitors.
AB  - Nitric oxide (NO) signaling plays a key role in modulating vascular tone and
      remodeling in the pulmonary circulation. The guanylate cyclase/cyclic guanylate
      monophosphate-signaling pathway primarily mediates nitric oxide signaling. This
      pathway is critical in normal regulation of the pulmonary vasculature, and is an
      important target for therapy in patients with pulmonary hypertension. In the
      pulmonary vasculature, degradation of cGMP is primarily regulated by PDE-5, and
      inhibition of this enzyme has important effects on pulmonary vasculature smooth
      muscle tone. Large randomized placebo-controlled trials of PDE-5 inhibitors
      demonstrated improved exercise capacity, hemodynamics and quality of life in
      adult patients with PAH. This chapter will discuss the mechanisms of NO signaling
      in the vasculature, characteristics of the PDE5-inhibitors approved for treatment
      of PH, and review available data on the use of phosphodiesterase inhibitors in
      PH. 

PMID- 24092344
TI  - Inhaled nitric oxide for the treatment of pulmonary arterial hypertension.
AB  - Following the recognition of nitric oxide (NO) as the "endothelium-derived
      relaxing factor," an explosion of laboratory and clinical research led to the
      development of inhaled NO as a potential therapy for patients with pulmonary
      arterial hypertension (PAH). Despite clear demonstration of its selective and
      potent pulmonary vasodilator properties, inhaled NO therapy has only been
      formally approved by the US Food and Drug Administration and European Medicine
      Evaluation Agency for clinical use in the treatment of term and near-term infants
      with severe persistent pulmonary hypertension of the newborn (PPHN) with acute
      hypoxemic respiratory failure. Over the past decades, inhaled NO remains the
      central therapy for PPHN and is commonly used for acute pulmonary vasoreactivity
      testing during right heart catheterization and for treating pediatric and adult
      patients with PAH associated with postoperative cardiac surgery, severe
      respiratory failure, pulmonary hypertension crises, and other disorders. This
      review will describe the current use of inhaled NO in clinical practice and
      briefly discuss its potential role for the treatment of chronic PAH. 

PMID- 24092345
TI  - Soluble guanylate cyclase stimulators in pulmonary hypertension.
AB  - Soluble guanylate cyclase (sGC) is a key enzyme in the nitric oxide (NO)
      signalling pathway. On binding of NO to its prosthetic haem group, sGC catalyses
      the synthesis of the second messenger cyclic guanosine monophosphate (cGMP),
      which promotes vasodilation and inhibits smooth muscle proliferation, leukocyte
      recruitment, platelet aggregation and vascular remodelling through a number of
      downstream mechanisms. The central role of the NO-sGC-cGMP pathway in regulating
      pulmonary vascular tone is demonstrated by the dysregulation of NO production,
      sGC activity and cGMP degradation in pulmonary hypertension (PH). The sGC
      stimulators are novel pharmacological agents that directly stimulate sGC, both
      independently of NO and in synergy with NO. Optimisation of the first sGC
      stimulator, YC-1, led to the development of the more potent and more specific sGC
      stimulators, BAY 41-2272, BAY 41-8543 and riociguat (BAY 63-2521). Other sGC
      stimulators include CFM-1571, BAY 60-4552, vericiguat (BAY 1021189), the
      acrylamide analogue A-350619 and the aminopyrimidine analogues. BAY 41-2272, BAY
      41-8543 and riociguat induced marked dose-dependent reductions in mean pulmonary
      arterial pressure and vascular resistance with a concomitant increase in cardiac
      output, and they also reversed vascular remodelling and right heart hypertrophy
      in several experimental models of PH. Riociguat is the first sGC stimulator that
      has entered clinical development. Clinical trials have shown that it
      significantly improves pulmonary vascular haemodynamics and increases exercise
      ability in patients with pulmonary arterial hypertension (PAH), chronic
      thromboembolic PH and PH associated with interstitial lung disease. Furthermore,
      riociguat reduces mean pulmonary arterial pressure in patients with PH associated
      with chronic obstructive pulmonary disease and improves cardiac index and
      pulmonary vascular resistance in patients with PH associated with left
      ventricular systolic dysfunction. These promising results suggest that sGC
      stimulators may constitute a valuable new therapy for PH. Other trials of
      riociguat are in progress, including a study of the haemodynamic effects and
      safety of riociguat in patients with PH associated with left ventricular
      diastolic dysfunction, and long-term extensions of the phase 3 trials
      investigating the efficacy and safety of riociguat in patients with PAH and
      chronic thromboembolic PH. Finally, sGC stimulators may also have potential
      therapeutic applications in other diseases, including heart failure, lung
      fibrosis, scleroderma and sickle cell disease. 

PMID- 24092346
TI  - Therapeutics targeting of dysregulated redox equilibrium and endothelial
      dysfunction.
AB  - All forms of WHO Group 1 PAH share a progressive and complex vasculopathy. At the
      center of this derangement lies the pulmonary vascular endothelium, which plays a
      crucial role in maintaining a delicate and precise balance of opposing
      vasoconstricting and vasodilating forces. In PAH, endothelial cell damage and
      dysfunction alter vascular homeostasis in favor of vasoconstriction. There is
      evidence of increased expression and activity in the vasoconstrictor and mitogen
      endothelin-1 signaling system and a decreased production of the potent
      vasodilator prostacyclin. These pathways have been a major focus of FDA approved
      PAH-specific therapies. Beyond these pathways, there is the dysfunction within
      the endothelial nitric oxide (NO) synthase signaling pathway and dysregulation of
      reactive oxygen and nitrogen species (ROS) that contribute to the pathogenesis of
      PAH. The dysregulation of vasodilator systems in PAH in large part involves the
      NO pathway, with almost every step subject to impairments. This includes a
      reduction in endothelial NO synthase function (eNOS), the enzymatic "uncoupling"
      of eNOS, increased scavenging of NO by superoxide and cell-free hemoglobin, the
      elaboration of endogenous competitive inhibitors of eNOS (ADMA), and the
      oxidation of the NO target, soluble guanylyl cyclase. The dysregulation of NO
      signaling pathways occurs in the setting of parallel upregulation of vascular
      oxidases that generate ROS. Enzymatic sources of ROS in PH that have been
      identified include the NAPDPH oxidases 1, 2, and 4, xanthine oxidase, uncoupled
      eNOS, and complex III of the mitochondrial electron transport chain. Superoxide
      produced from these sources reacts with NO to form the reactive nitrogen species
      peroxynitrate, further diverting bioavailable NO to more injuries species. In
      PAH, this upstream dysregulation of ROS/NO redox homeostasis severely impairs
      vascular tone and contributes to the pathological activation of mitogenic
      pathways, leading to cellular proliferation and obliteration of the pulmonary
      vasculature. Therapeutic strategies are being evaluated that target the
      associated dysregulated redox equilibrium and endothelial dysfunction in PAH.
      Therapeutic interventions reviewed in this chapter include NO donor or NO
      generating drugs, therapies that recouple eNOS or directly increase cGMP levels
      via inhibition of phosphodiesterase 5 or stimulation of soluble guanylyl cyclase,
      and therapies that inhibit vascular oxidases or scavenge ROS. 

PMID- 24092347
TI  - Rho-kinase inhibitors.
AB  - Pulmonary arterial hypertension (PAH) is a fatal disease with poor prognosis
      characterized by progressive elevation of pulmonary arterial pressure and
      vascular resistance due to pulmonary artery hyperconstriction and remodeling;
      however, the precise mechanism of PAH still remains to be elucidated. Although
      anticoagulant agents, pulmonary vasodilators, and lung transplantation are
      currently used for the treatment of PAH, more effective treatment needs to be
      developed. Rho-kinase causes vascular smooth muscle hyperconstriction and
      vascular remodeling through inhibition of myosin phosphatase and activation of
      its downstream effectors. In a series of experimental and clinical studies, it
      has been demonstrated that Rho-kinase-mediated pathway plays an important role in
      various cellular functions not only in vascular smooth muscle hyperconstriction
      but also in actin cytoskeleton organization, cell adhesion and motility,
      cytokinesis, and gene expressions, all of which may be involved in the
      pathogenesis of arteriosclerosis. Rho-kinase is activated in animal models of PAH
      (monocrotaline and chronic hypoxia) associated with enhanced pulmonary
      vasoconstriction and proliferation, impaired endothelial vasodilator functions,
      and pulmonary remodeling. Therapeutic application of Rho-kinase inhibitors
      reverses established experimental pulmonary hypertension. Further, administration
      or inhalation of Rho-kinase inhibitors exerts acute pulmonary vasodilation in
      patients with PAH who were refractory to conventional therapies. Taken together,
      Rho-kinase is a novel and important therapeutic target of PAH, and Rho-kinase
      inhibitors are a promising new class of drugs for this fatal disorder. 

PMID- 24092348
TI  - Serotonin transporter and serotonin receptors.
AB  - The nature of the primary defect responsible for triggering and maintaining
      pulmonary artery smooth muscle (PA-SMC) proliferation in pulmonary artery
      hypertension (PAH) is poorly understood but may be either an inherent
      characteristic of PA-SMCs or a secondary response to an external abnormality,
      such as upregulation of growth factors. The serotonin hypothesis of PAH
      originated in the 1960s after an outbreak of the disease was reported among
      patients taking the anorexigenic drugs aminorex. The anorexiant dexfenfluramine
      which inhibits 5-HT neuronal uptake, causes 5-HT platelet depletion, and
      increases plasma levels of 5-HT, was then shown to increase the relative risk of
      developing PAH in the adults. More recently, the incidence of persistent
      pulmonary hypertension of the newborn was shown to be increased by the use of
      selective 5-HT reuptake inhibitors taken in late pregnancy. Serotonin is a
      vasoconstrictor and a potent mitogen for pulmonary smooth muscle cells (PA-SMC),
      an effect which depends upon activity of both the 5-HT transporter (5-HTT) and
      the 5-HT receptors. Expression analysis of lung tissues from PAH patients
      undergoing lung transplantation revealed an increased expression of the 5-HT
      transporter (5-HTT) and an enhanced proliferative growth response of isolated
      pulmonary arterial smooth muscle cells (PASMC) to 5-HT. Serotonin is contained in
      platelets but is also synthesized by pulmonary endothelial cells which express
      tryptophan hydroxylase 1, the rate-limiting enzyme of 5-HT synthesis. While
      inhibitors of 5-HTT and of 5-HT2B receptors can reverse experimental PH, 5-HTT
      overexpressing mice spontaneously develop PH. In patients with chronic lung
      disease, a close association has been found between a 5-HTT gene polymorphism and
      the severity of pulmonary hypertension. Agents capable of selectively inhibiting
      5-HTT-mediated PA-SMC proliferation deserve to be investigated as potential
      treatments for pulmonary hypertension. However, the 5-HT pathway is still studied
      only on a preclinical level and the usefulness of drugs interacting with the 5-HT
      pathway remains to be established in human PAH. 

PMID- 24092349
TI  - Targeting of platelet-derived growth factor signaling in pulmonary arterial
      hypertension.
AB  - Despite recent advances in the management of patients with pulmonary arterial
      hypertension (PAH), this disease remains a devastating condition with limited
      survival. While the current therapies primarily target the
      vasoconstrictor/vasodilator imbalance in the pulmonary circulation, there is
      currently no cure for PAH, and pulmonary vascular remodeling-representing the
      underlying cause of the disease-is only modestly affected. Hence, novel
      therapeutic approaches directly targeting the vascular remodeling process are
      warranted. Recent studies provided compelling evidence that peptide growth
      factors, which elicit their signals via receptor tyrosine kinases, are important
      contributors to the development and progression of PAH. In particular, platelet
      derived growth factor (PDGF) is a strong mitogen for pulmonary vascular smooth
      muscle cells and protects these cells from apoptosis, thus representing an
      important mediator of pulmonary vascular remodeling. PDGF ligand and receptors
      are upregulated in PAH, and experimental studies have shown that inhibition of
      PDGF receptor signaling by pharmacological or genetic approaches prevents the
      development of PAH in animal models and is even able to reverse pulmonary
      vascular remodeling once it has been established. Consistently, results from
      phase II and phase III clinical trials indicate that the tyrosine kinase
      inhibitor imatinib mesylate, which potently inhibits the PDGF receptor, is
      effective in improving exercise capacity and pulmonary hemodynamics as add-on
      therapy in patients with severe PAH (i.e., pulmonary vascular resistance >800
      dynes s cm(-5)). Future studies will evaluate the long-term clinical efficacy and
      safety of imatinib, including patients with less impaired hemodynamics. Based on
      the current knowledge, targeting of PDGFR signaling is likely to become an anti
      proliferative treatment option for patients with PAH and has the potential to at
      least partially correct the pathology of the disease. 

PMID- 24092350
TI  - Emerging molecular targets for anti-proliferative strategies in pulmonary
      arterial hypertension.
AB  - The combination of pulmonary vasoconstriction, in situ thrombosis, and pulmonary
      arterial wall remodeling is largely responsible for the rise in pulmonary
      vascular resistance (PVR) and pulmonary arterial pressure (PAP) in patients with
      pulmonary arterial hypertension (PAH). Even though several drugs have been
      developed over the past decades, at this time there is no cure for PAH. The
      overriding goals of the current therapeutic options seek to compensate for the
      defects in the relative balance of competing vasoconstrictor and vasodilator
      influences. Because the past decade has seen great strides in our understanding
      of the pathogenesis of PAH, interest has been growing in the potential use of
      anti-proliferative approaches in PAH. Indeed anti-proliferative strategies could
      offer ways not only to reinstate the homeostatic balance between cell
      proliferation and apoptosis but also to reverse the progressive pulmonary
      vascular obstruction in PAH. However, further efforts still need to be made in
      order to establish the long-term safety and efficacy of those anti-proliferative
      approaches in PAH and their potential additive benefit with other drugs. 

PMID- 24092351
TI  - Anti-inflammatory and immunosuppressive agents in PAH.
AB  - Pulmonary arterial hypertension (PAH) pathobiology involves a remodeling process
      in distal pulmonary arteries, as well as vasoconstriction and in situ thrombosis,
      leading to enhanced pulmonary vascular resistance and pressure, to right heart
      failure and death. The exact mechanisms accounting for PAH development remain
      unknown, but growing evidence demonstrate that inflammation plays a key role in
      triggering and maintaining pulmonary vascular remodeling. Not surprisingly, PAH
      is often associated with diverse inflammatory disorders. Furthermore, pathologic
      specimens from PAH patients reveal an accumulation of inflammatory cells in and
      around vascular lesions, including macrophages, T and B cells, dendritic cells,
      and mast cells. Circulating levels of autoantibodies, chemokines, and cytokines
      are also increased in PAH patients and some of these correlate with disease
      severity and patients' outcome. Moreover, preclinical experiments demonstrated
      the key role of inflammation in PAH pathobiology. Immunosuppressive agents have
      also demonstrated beneficial effects in animal PAH models. In humans,
      observational studies suggested that immunosuppressive drugs may be effective in
      treating some PAH subtypes associated with marked inflammation. The present
      chapter reviews experimental and clinical evidence suggesting that inflammation
      is involved in the pathogenesis of PAH, as well the therapeutic potential of
      immunosuppressive agents in PAH. 

PMID- 24092352
TI  - Vasoactive peptides and the pathogenesis of pulmonary hypertension: role and
      potential therapeutic application.
AB  - Pulmonary hypertension (PH) is a debilitating disease with a dismal prognosis.
      Recent advances in therapy (e.g. prostacyclin analogues, endothelin receptor
      antagonists and phosphodiesterase 5 inhibitors), whilst significantly improving
      survival, simply delay the inexorable progression of the disease. An array of
      endogenous vasoconstrictors and vasodilators coordinates to maintain pulmonary
      vascular homeostasis and morphological integrity, and an imbalance in the
      expression and function of these mediators precipitates PH and related lung
      diseases. The vasodilator peptides, including natriuretic peptides, vasoactive
      intestinal peptide, calcitonin gene-related peptide and adrenomedullin, trigger
      the production of cyclic nucleotides (e.g. cGMP and cAMP) in many pulmonary cell
      types, which in tandem exert a multifaceted protection against the pathogenesis
      of PH, encompassing vasodilatation, inhibition of vascular smooth muscle
      proliferation, anti-inflammatory and anti-fibrotic effects and salutary actions
      on the right ventricle. This coordinated beneficial activity underpins a
      contemporary perception that to advance treatment of PH it is necessary to offset
      multiple disease mechanisms (i.e. the pulmonary vasoconstriction, pulmonary
      vascular remodelling, right ventricular dysfunction). Thus, there is considerable
      potential for harnessing the favourable activity of peptide mediators to offer a
      novel, efficacious therapeutic approach in PH. 

PMID- 24092353
TI  - Pulmonary hypertension: novel pathways and emerging therapies inhibitors of cGMP
      and cAMP metabolism.
AB  - Cyclic nucleotides (e.g., cAMP and cGMP) are ubiquitous second messengers that
      affect multiple cell functions including vascular tone and vascular cell
      proliferation. After production, different processes can regulate the
      concentration of cyclic nucleotides. Cyclic nucleotides' degradation by
      phosphodiesterase (PDE) enzymes has well-known roles in regulating cyclic
      nucleotides concentrations. Recently, recognition of ATP-binding cassette (ABC)
      transporter contribution to both local and global regulation of cAMP has been
      acknowledged. Recent data support an important role of cyclic nucleotide efflux
      in the pathobiology of pulmonary hypertension, thus suggesting that inhibition of
      cyclic nucleotide efflux proteins might be a useful strategy to prevent and treat
      PH. 

PMID- 24092354
TI  - Pulmonary hypertension: old targets revisited (statins, PPARs, beta-blockers).
AB  - Pulmonary arterial hypertension is a therapeutic challenge. Despite progress in
      recent years with three drug classes-prostanoids, endothelin receptor antagonists
      and phosphodiesterase type 5 inhibitors-long-term patient survival remains poor.
      Importantly, the introduction and commercial success of these new treatments has
      been accompanied by growing interest in the pathology of pulmonary hypertension.
      This, in turn, has stimulated a re-evaluation of the molecular factors driving
      the structural remodelling of pulmonary arterioles and the opportunities to
      preserve right ventricular function in pulmonary hypertension. Academics with
      restricted access to new chemicals have turned to existing drugs to investigate
      new ideas. It is in this context that the role of statins, peroxisome
      proliferator-activated receptors (PPARs) and beta-blockers are of interest as
      potential treatments for pulmonary hypertension. 

PMID- 24092355
TI  - Pulmonary hypertension: current management and future directions.
AB  - Despite major advances in our understanding of the pathobiology of pulmonary
      vasculopathy and in the treatment of pulmonary vascular disease, pulmonary
      hypertension remains a severe condition that frequently progresses to right heart
      failure and death. This chapter will review several novel approaches to
      treatment, based on recent observations in both patients and experimental models,
      that may lead to new and more effective treatment approaches to pulmonary
      hypertension in the future. 

PMID- 24092356
TI  - Independent priming of location and color in identification of briefly presented
      letters.
AB  - Attention shifts are facilitated if the items to be attended remain the same
      across trials. Some researchers argue that this priming effect is perceptual,
      whereas others propose that priming is postperceptual, involving facilitated
      response selection. The experimental findings have not been consistent regarding
      the roles of variables such as task difficulty, response repetition,
      expectancies, and decision-making. Position priming, when repetition of a target
      position facilitates responses on a subsequent trial, is another source of
      disagreement among researchers. Experimental results have likewise been
      inconsistent as to whether position priming is dependent on the repetition of
      target features or has an independent effect on attention shifts. We attempted to
      isolate the perceptual components of priming by presenting brief (10-180 ms)
      search arrays to eight healthy observers. The task was to identify a color
      singleton letter among distractors. All stimulus presentation contingencies were
      randomized, and responses were unspeeded, to avoid effects of observer
      expectation and postperceptual effects. Repeating target color and/or position
      strongly improved performance. The effects of color and position repetition were
      independent of one another and were stable across participants. The results argue
      for a strong perceptual component in priming, which biases selection toward
      recent target features and positions, showing that perceptual mechanisms are
      sufficient to produce priming in visual search and that such effects can be
      elicited with limited sensory evidence. The results are the first to demonstrate
      independent priming of color and position in the identification of briefly
      presented, postmasked stimuli. 

PMID- 24092357
TI  - The assessment of subjective visual vertical: comparison of two psychophysical
      paradigms and age-related performance.
AB  - Perception of the subjective visual vertical (SVV) is usually assessed by asking
      to subjects, in complete darkness, to adjust the position of a luminous rod that
      is variably tilted (i.e., by the method of adjustment [ADJ]). Conversely, the two
      alternative forced choice (2AFC) method requires subjects to categorize, as
      tilted either clockwise (CW) or counterclockwise (CCW), stimuli that are
      presented on a computer screen and are variably tilted from vertical. In this
      study, we aimed to compare the results of these two methods and investigate age
      related effects on the SVV. SVV was assessed in 102 healthy individuals, 50 women
      and 52 men, with a mean age of 45.7 (range 20-91), using both ADJ (ten trials,
      initial 1 degrees , 2 degrees , 4 degrees , 8 degrees , or 12 degrees  bar tilts
      both CW and CCW) and 2AFC (120 stimuli with a 1 degrees -32 degrees  variable
      tilt). Also, 50 of the subjects performed the ADJ test twice, with different bar
      lengths. We estimated bias and threshold for the two methods, and found that
      neither measure differed across the methods. Age was a significant predictor of
      threshold (2AFC, R (2) = .141; ADJ, R (2) = .190; p < .001), implying lower
      sensitivity with increasing age. Moreover, the ADJ method showed a significant
      increase of bias when the initial tilt was farthest from vertical, whereas the
      rod length was irrelevant. SVV measures obtained with the ADJ and 2AFC methods
      were comparable, but the latter measures were more resistant to artifacts that
      might affect the measurement. The lower sensitivity found in older persons may
      have an influence on their ability to interact with the environment and may
      contribute to impairment of postural control. 

PMID- 24092358
TI  - Body position differentially influences responses to exogenous and endogenous
      cues.
AB  - The influence of vestibular inputs on exogenous (Exp. 1) and endogenous (Exp. 2)
      orienting of visual attention was examined. The vestibular system was manipulated
      through a change in static body position. Participants engaged in an exogenous or
      endogenous response task while in a seated position, while lying in a prone
      position, and while in a prone position with their head down and neck flexed
      (HDNF). An attenuation of inhibition and facilitation effects during the
      exogenous task was observed in the HDNF position. However, responses to the cues
      remained similar in the endogenous task, irrespective of body position. The
      results reveal a potential dissociation between reflexive and volitional
      orienting of visual attention that is dependent on vestibular inputs. 

PMID- 24092359
TI  - Word length effects on novel words: evidence from eye movements.
AB  - The present study investigated the effects of word length on eye movement
      behavior during initial processing of novel words while reading. Adult skilled
      readers' eye movements were monitored as they read novel or known target words in
      sentence frames with neutral context preceding the target word. Comparable word
      length effects on all single-fixation measures for novel and known words
      suggested that both types of words were subject to similar initial encoding
      strategies. The impact of the absence of an existing lexical entry emerged in
      multiple first-pass fixation measures in the form of interactions between word
      length (long and short) and word type (novel and known). Specifically, readers
      spent significantly more first-pass time refixating long novel targets than short
      novel targets; however, the first-pass time spent refixating known controls did
      not differ as a function of length. Implications of these findings for models of
      eye movement control while reading, as well as for vocabulary acquisition in
      reading, are discussed. 

PMID- 24092360
TI  - Attentional priming releases crowding.
AB  - Views of natural scenes unfold over time, and objects of interest that were
      present a moment ago tend to remain present. While visual crowding places a
      fundamental limit on object recognition in cluttered scenes, most studies of
      crowding have suffered from the limitation that they typically involved static
      scenes. The role of temporal continuity in crowding has therefore been
      unaddressed. We investigated intertrial effects upon crowding in visual scenes,
      showing that crowding is considerably diminished when objects remain constant on
      consecutive visual search trials. Repetition of both the target and distractors
      decreases the critical distance for crowding from flankers. More generally, our
      results show how object continuity through between-trial priming releases objects
      that would otherwise be unidentifiable due to crowding. Crowding, although it is
      a significant bottleneck on object recognition, can be mitigated by statistically
      likely temporal continuity of the objects. Crowding therefore depends not only on
      what is momentarily present, but also on what was previously attended. 

PMID- 24092361
TI  - Ischemic heart diseases in Egypt: role of xanthine oxidase system and ischemia
      modified albumin.
AB  - It is known that xanthine oxidoreductase contributes significantly to
      ischemia/reperfusion injury by generating reactive oxygen species. Ischemia
      modified albumin (IMA) is a biomarker of acute myocardial ischemia with high
      sensitivity but moderate specificity. Our study aims to evaluate the xanthine
      oxidase (XO) system and the IMA level in the serum of patients with ischemic
      heart disease, and their correlation with traditional cardiac markers. The study
      was conducted on 60 patients with ischemic heart disease and 22 healthy subjects
      (control group). Subjects were divided into three groups: group I (30 patients
      with ST-elevated myocardial infarction), group II (30 patients with chronic
      stable angina), and the control group (22 subjects). The patients and controls
      had laboratory tests performed including lipid profile, cardiac enzymes, XO, uric
      acid, and IMA. The serum levels of XO and IMA were significantly higher in group
      I (1.65 +/- 0.29 U/ml and 0.58 +/- 0.15 ABSU, respectively) than in group II
      (1.11 +/- 0.20 U/ml and 0.29 +/- 0.10 ABSU, respectively) and the control group
      (0.95 +/- 0.16 U/ml and 0.24 +/- 0.08 ABSU, respectively) (P < 0.001). There was
      a significant positive correlation between XO and IMA in group I. Also, there was
      significant positive correlation between XO or IMA and other cardiac markers,
      with the highest level of significance between IMA and creatine kinase (CK-MB).
      In group II only XO activity was significantly elevated in comparison with
      controls. These results confirm the role of XO enzyme in ischemic heart disease
      with involvement of IMA, at a detectable level, during the early necrotic phase.

PMID- 24092362
TI  - Baseline cardiac magnetic resonance imaging versus baseline endomyocardial biopsy
      for the prediction of left ventricular reverse remodeling and prognosis in
      response to therapy in patients with idiopathic dilated cardiomyopathy.
AB  - Endomyocardial biopsy (EMB) and late gadolinium enhancement cardiovascular
      magnetic resonance (LGE-CMR) imaging performed at baseline are both used to
      evaluate the extent of myocardial fibrosis. However, no study has directly
      compared the effectiveness of these diagnostic tools in the prediction of left
      ventricular reverse remodeling (LVRR) and prognosis in response to therapy in
      patients with idiopathic dilated cardiomyopathy (IDCM). Seventy-five patients
      with newly diagnosed IDCM who were undergoing optimal therapy were assessed at
      baseline using LGE-CMR imaging and EMB; the former measured LGE area and the
      latter measured collagen volume fraction (CVF) as possible predictive indices of
      LVRR and cardiac event-free survival. Among all the baseline primary candidate
      factors with P < 0.2 as per univariate analysis, multivariate analysis indicated
      that only LGE area was an independent predictor of subsequent LVRR (beta = 0.44;
      95 % confidence interval (CI) 0.87-2.53; P < 0.001), as indicated by decreasing
      left ventricular end-systolic volume index over the 1-year follow-up. Kaplan
      Meier curves indicated significantly lower cardiac event-free survival rates in
      patients with LGE at baseline than in patients without (P < 0.01). By contrast,
      there was no significant difference in prognosis between patients with CVF values
      above (severe fibrosis) and below (mild fibrosis) the median of 4.9 %. Cox
      proportional hazard analysis showed that LGE area was an independent predictor of
      subsequent cardiac events (hazard ratio 1.06; 95 % CI 1.02-1.10; P <= 0.01). The
      degree of myocardial fibrosis estimated by baseline LGE-CMR imaging, but not that
      estimated by baseline EMB, can predict LVRR and cardiac event-free survival in
      response to therapy in patients with newly diagnosed IDCM. 

PMID- 24092363
TI  - Low efficacy of cardioversion of persistent atrial fibrillation with the
      implantable cardioverter-defibrillator.
AB  - AIMS: Atrial fibrillation (AF) and heart failure are conditions that often
      coexist. Consequently, many patients with an implantable cardioverter
      defibrillator (ICD) present with AF. We evaluated the effectiveness of internal
      cardioversion of AF in patients with an ICD. METHODS: Retrospectively, we
      included 27 consecutive ICD patients with persistent AF who underwent internal
      cardioversion using the ICD. When ICD cardioversion failed, external
      cardioversion was performed. RESULTS: Patients were predominantly male (89 %)
      with a mean (SD) age of 65 +/- 9 years and left ventricular ejection fraction of
      36 +/- 17 %. Only nine (33 %) patients had successful internal cardioversion
      after one, two or three shocks. The remaining 18 patients underwent external
      cardioversion after they failed internal cardioversion, which resulted in sinus
      rhythm in all. A smaller left atrial volume (99 +/- 36 ml vs. 146 +/- 44 ml; p =
      0.019), a longer right atrial cycle length (227 (186-255) vs. 169 (152-183) ms, p
      = 0.030), a shorter total AF history (2 (0-17) months vs. 40 (5-75) months, p =
      0.025) and dual-coil ICD shock (75 % vs. 26 %, p = 0.093) were associated with
      successful ICD cardioversion. CONCLUSION: Internal cardioversion of AF in ICD
      patients has a low success rate but may be attempted in those with small atria, a
      long right atrial fibrillatory cycle length and a short total AF history,
      especially when a dual-coil ICD is present. Otherwise, it seems reasonable to
      prefer external over internal cardioversion when it comes to termination of
      persistent AF.

PMID- 24092364
TI  - Overview of cytopathology procedures and techniques.

PMID- 24092365
TI  - Ancillary studies on neoplastic cytologic specimens.

PMID- 24092366
TI  - Head and neck.

PMID- 24092367
TI  - Cytology of the lung.

PMID- 24092368
TI  - Liver cytology.

PMID- 24092369
TI  - Esophagus, stomach, and pancreas.

PMID- 24092370
TI  - Genitourinary cytopathology (kidney and urinary tract).
AB  - FNA of kidney masses have been performed for the diagnosis of mass
      lesions,confirmation of advanced neoplasia and metastases, and staging of tumors.
      In the past, the decision of whether to perform a nephrectomy used to be based on
      radiographic features and size, precluding the use of FNA. Today, where treatment
      is not limited to surgery alone, the indications for renal FNA have expanded.
      Most small renal masses are asymptomatic and are detected incidentally due to
      improved imaging techniques. Although most urologists agree that the standard of
      care for renal masses is surgery, if the patient is an elderly individual, or has
      comorbidities a preoperative FNA could be useful in guiding the management.When
      we look at data from large referral institutions such as Mayo Clinic, Johns
      Hopkins Medical Institutions, and the Cleveland Clinic approximately 30 %of the
      renal masses are benign [86---88]. Therefore, as astutely pointed out by Volpe et
      al.[3], there is a role for precise pretreatment characterization of the renal
      masses by FNA, which would decrease the unnecessary treatment for benign diseases
      and reduce the treatment-related mortality and morbidity in addition to reducing
      patient care costs.To date, urine cytology remains the gold standard for bladder
      cancer screening.It has been, and still is, the test against which all new tests
      are compared when evaluating potential bladder tumor markers. The answer to
      whether urine cytology possesses the optimal combination of sensitivity and
      specificity to retain consideration as the best screening device depends on the
      goals of the practice. Urine cytology has excellent specificity with only few
      false-positive cases. Its overall sensitivity (including both high grade and low
      grade lesions) is poor, but this is explained by poor criteria for identifying
      well-differentiated, low-grade urothelial carcinoma in cytology. The natural
      history of low grade lesions is that of multiple superficial recurrences in 70 -
      80 % of patients, with only a minority ( 10-15 %)progressing to muscle invasive
      or metastatic disease [89]. Patients with low-grade urothelial carcinoma are at
      low risk for progression, they are monitored primarily for the development of a
      subsequent high grade tumor [90]. Therefore, as suggested by Koss, detection of
      new low-grade lesions may be clinically irrelevant as compared to early detection
      of disease progression [39]. Contrary to the low grade lesions, however, urine
      cytology often results in the identification of high-grade malignant cells even
      before a cystoscopically distinguishable gross lesion is present. In the last 20
      years, a number of noninvasive test have been developed to detect urothelial
      carcinoma. Although some have been able to show a better sensitivity compared to
      cytology, only a few have been close to reaching the sensitivity seen in
      cytology. Most of these tests have not added much to the diagnostic evaluation.
      Combining some of the new markers with each other and/or cytologic evaluation may
      optimize their performance status.

PMID- 24092371
TI  - Body cavity fluids.

PMID- 24092372
TI  - Cytopathology in the diagnosis of lymphoma.
AB  - FNA is a simple, safe, and an inexpensive sampling technique that plays an
      important role in the evaluation of lymphadenopathy. The key to enhancing the
      accuracy of FNA diagnosis of lymphoma is the multi parameter approach in which
      the cytomorphologic features are evaluated in correlation with the results of
      ancillary studies and clinical context. A full understanding of the current
      lymphoma classification, clinical features associated with each lymphoma subtype
      and the impact of the diagnosis on patient management is essential in FNA
      diagnosis of lymphoma. It is also important to recognize the limitations of FNA
      in the primary diagnosis of some subtypes of lymphoma, and tissue biopsy should
      be recommended for a definitive diagnosis and subclassification in such cases.

PMID- 24092373
TI  - Female genital tract.

PMID- 24092374
TI  - Beyond the standard of care: the role of cytopathology in molecular testing of
      cancer.

PMID- 24092375
TI  - Macrophages and transplant rejection: a novel future target?
AB  - In this issue of Transplantation, Ma et al. describe the protective effect of
      administering the c-fms kinase inhibitor upon cellular rejection, suggesting an
      important pathogenic role for macrophages. In contrast, no effect upon the
      development of humerol rejection was evident. The role of macrophages in
      rejection is discussed.

PMID- 24092376
TI  - An international survey of cytomegalovirus prevention and treatment practices in
      intestinal transplantation.
AB  - BACKGROUND: Practice variation regarding cytomegalovirus (CMV) prevention and
      treatment across intestinal transplantation (IT) programs is unknown. METHODS: An
      electronic survey was sent to IT programs registered with the Intestinal
      Transplant Association. Proportions were analyzed for categorical variables;
      means and SDs were analyzed for continuous variables. RESULTS: Seventy-seven
      percent of IT programs responded to the survey. For CMV D+/R- recipients, 39.1%
      programs used universal prophylaxis (UP), 8.7% preemptive strategy (PE), and
      52.2% hybrid strategy. For CMV R+ recipients, 45.8% programs used UP, 12.5% PE,
      37.1% hybrid strategy, and 4.2% none. For CMV D-/R- recipients, 39.1% programs
      used UP, 21.7% PE, 26.1% hybrid strategy, and 13% none. Frequency of monitoring
      for PE was weekly 71.4% of programs, every 2 weeks 21.4%, and monthly 7.1%. For
      CMV viremia, syndrome and disease, the most common first-line agents used were
      ganciclovir (100% and 96.2%) and valganciclovir (23.1%) and the second-line agent
      was foscarnet (73.1% and 84.6%). Immunoglobulins were administered in 65.4% of
      the programs for pneumonia (69.2%), meningoencephalitis (50%), enteritis (46.2%),
      colitis (38.5%), syndrome (42.3%), viremia (30.8%), and resistant/refractory
      infections (11.5%). CONCLUSIONS: Prophylaxis and hybrid strategy were the most
      commonly used. Treatment practices were consistent and mainly involved
      ganciclovir as first-line agent and foscarnet as second-line agent. The use of
      immunoglobulins appeared to be more common than in other allografts.

PMID- 24092377
TI  - Rapamycin enhances long-term hematopoietic reconstitution of ex vivo expanded
      mouse hematopoietic stem cells by inhibiting senescence.
AB  - BACKGROUND: The mammalian target of rapamycin (mTOR) is an important regulator of
      hematopoietic stem cell (HSC) self-renewal and its overactivation contributes to
      HSC premature exhaustion in part via induction of HSC senescence. Inhibition of
      mTOR with rapamycin has the potential to promote long-term hematopoiesis of ex
      vivo expanded HSCs to facilitate the clinical application of HSC transplantation
      for various hematologic diseases. METHODS: A well-established ex vivo expansion
      system for mouse bone marrow HSCs was used to investigate whether inhibition of
      overactivated mTOR with rapamycin can promote long-term hematopoiesis of ex vivo
      expanded HSCs and to elucidate the mechanisms of action of rapamycin. RESULTS:
      HSC-enriched mouse bone marrow LSK cells exhibited a time-dependent activation of
      mTOR after ex vivo expansion in a serum-free medium supplemented with stem cell
      factor, thrombopoietin, and Flt3 ligand. The overactivation of mTOR was
      associated with induction of senescence but not apoptosis in LSK cells and a
      significant reduction in the ability of HSCs to produce long-term hematopoietic
      reconstitution. Inhibition of overactivated mTOR with rapamycin promoted ex vivo
      expansion and long-term hematopoietic reconstitution of HSCs. The increase in
      long-term hematopoiesis of expanded HSCs is likely attributable in part to
      rapamycin-mediated up-regulation of Bmi1 and down-regulation of p16, which
      prevent HSCs from undergoing senescence during ex vivo expansion. CONCLUSIONS:
      These findings suggest that mTOR plays an important role in the regulation of HSC
      self-renewal in vitro and inhibition of mTOR hyperactivation with rapamycin may
      represent a novel approach to promote ex vivo expansion and their long-term
      hematopoietic reconstitution of HSCs.

PMID- 24092378
TI  - Enhanced suppression of the xenogeneic T-cell response in vitro by xenoantigen
      stimulated and expanded regulatory T cells.
AB  - BACKGROUND: Strategies to prevent xenograft rejection while minimizing long-term
      immunosuppression need to be developed for successful xenotransplantaion.
      Polyclonally expanded human regulatory T cells (Treg) are known to suppress
      xenogeneic responses in vivo and in vitro. However, the risk of opportunistic
      infection and malignancy and the requirement for large numbers of Treg for
      effective suppression remain drawbacks to their clinical application. This study
      aimed to expand human Treg with xenoantigen stimulation and to assess their
      effectiveness at suppressing the xenoimmune response. METHODS: Human CD4CD25CD127
      Treg were stimulated with anti-CD3/CD28 beads, interleukin (IL)-2, and rapamycin
      for polyclonal expansion. After 7 days, Treg were further expanded with two
      subsequent cycles of either polyclonal stimulation or xenoantigen stimulation
      with irradiated porcine peripheral blood mononuclear cells with or without anti
      pig SLA CII monoclonal antibody. Treg phenotype and suppressive capacity were
      assessed after xenoantigen stimulation. RESULTS: Porcine xenoantigen-stimulated
      Treg retained Treg phenotype but had an increased expression of human leukocyte
      antigen-DR, inducible costimulator, and CD45RO when compared with their
      polyclonally stimulated counterparts. In a pig-human mixed lymphocyte reaction
      (MLR), xenoantigen-stimulated Treg demonstrated an enhanced suppressive capacity
      at higher ratios of responder cells:Treg and secreted higher concentrations of IL
      10 and IL-35, although they were equally suppressive as polyclonally stimulated
      Treg in an allogeneic or polyclonal MLR. When Treg expanded in the presence of
      anti-pig SLA monoclonal antibody were used in the same pig-human MLR, their
      suppressive capacity was reduced substantially. CONCLUSIONS: Xenoantigen
      stimulated Treg show enhanced suppressive capacity in the pig-human MLR most
      likely via an IL-10-mediated pathway.

PMID- 24092379
TI  - Randomized controlled trial comparing hand-assisted retroperitoneoscopic versus
      standard laparoscopic donor nephrectomy.
AB  - BACKGROUND: Laparoscopic donor nephrectomy (LDN) has become the gold standard for
      live-donor nephrectomy, as it results in a short convalescence time and increased
      quality of life. However, intraoperative safety has been debated, as severe
      complications occur incidentally. Hand-assisted retroperitoneoscopic donor
      nephrectomy (HARP) is an alternative approach, combining the safety of hand
      guided surgery with the benefits of endoscopic techniques and retroperitoneal
      access. We assessed the best approach to optimize donors' quality of life and
      safety. METHODS: In two tertiary referral centers, donors undergoing left-sided
      nephrectomy were randomly assigned to HARP or LDN. Primary endpoint was physical
      function, one of the dimensions of the Short Form-36 questionnaire on quality of
      life, at 1 month postoperatively. Secondary endpoints included intraoperative
      events and operation times. Follow-up was 1 year. RESULTS: In total, 190 donors
      were randomized. Physical function at 1 month follow-up did not significantly
      differ between groups (estimated difference, 1.79; 95% confidence interval, -4.1
      to 7.68; P=0.55). HARP resulted in significantly shorter skin-to-skin time (mean,
      159 vs. 188 min; P<0.001), shorter warm ischemia time (2 vs. 5 min; P<0.001) and
      a lower intraoperative event rate (5% vs. 11%, P=0.117). Length of stay (both 3
      days; P=0.135) and postoperative complication rate (8% vs. 8%; P=1.00) were not
      significantly different. Potential graft-related complications did not
      significantly differ (6% vs. 13%; P=0.137). CONCLUSIONS: Compared with LDN, left
      sided HARP leads to similar quality of life, shorter operating time, and warm
      ischemia time. Therefore, we recommend HARP as a valuable alternative to the
      laparoscopic approach for left-sided donor nephrectomy.

PMID- 24092380
TI  - Toxoplasma gondii serostatus is not associated with impaired long-term survival
      after heart transplantation.
AB  - BACKGROUND: Conflicting data have been reported about the effect of Toxoplasma
      serostatus on mortality after heart transplantation. Either a positive or a
      negative recipient Toxoplasma serostatus was found to be associated with
      increased mortality. METHODS: We evaluated the effects of T. gondii infection on
      survival of our 582 cardiac allograft recipients operated upon between June 1984
      and July 2011. RESULTS: The 258 Toxoplasma seronegative and 324 seropositive
      recipients differed in age, pretransplantation diagnosis, ischemia time, renal
      function, donor Toxoplasma serology, and maintenance immunosuppression. After a
      median follow-up time of 8.3 years (range, 0-26 years), 117 (45%) seronegative
      and 219 (67%) seropositive patients died. No difference was found in deaths due
      to cardiac allograft vasculopathy. After adjustment for all relevant clinical
      characteristics, the recipient Toxoplasma serostatus was not associated with
      mortality (hazard ratio, 1.21; 95% confidence interval [CI], 0.95-1.54). With the
      Toxoplasma serostatus combination donor negative/recipient negative as a
      reference, univariate hazard ratios for the Toxoplasma serostatus combinations
      were D+/R- 0.52 (95% CI, 0.37-0.73), D-/R+ 0.65 (95% CI, 0.40-1.05), and D+/R+
      0.78 (95% CI, 0.57-1.07). Multivariate analysis, however, showed that donor
      Toxoplasma serostatus was not independently associated with mortality.
      CONCLUSIONS: The Toxoplasma serostatus of both the recipient and donor appeared
      not to be independent risk factors for mortality after heart transplantation.

PMID- 24092381
TI  - Tubular atrophy and low netrin-1 gene expression are associated with delayed
      kidney allograft function.
AB  - BACKGROUND: Delayed graft function (DGF) caused by ischemia/reperfusion injury
      (I/RI) negatively influences the outcome of kidney transplantation. This
      prospective single-center study characterized the intrarenal transcriptome during
      I/RI as a means of identifying genes associated with DGF development. METHODS:
      Characterization of the intrarenal transcription profile associated with I/RI was
      carried out on three sequential graft biopsies from respective allografts before
      and during transplantation. The intragraft expression of 92 candidate genes was
      measured using quantitative real-time reverse transcriptase polymerase chain
      reaction (2) in delayed (n=9) and primary function allografts (n=26). RESULTS:
      Cold storage was not associated with significant changes to the expression
      profile of the target gene transcripts; however, up-regulation of 16 genes
      associated with enhanced activation of innate and adaptive immune responses and
      apoptosis was observed after reperfusion. Multivariate logistic regression
      analysis revealed that higher tubular atrophy scores (ct) together with a lower
      expression of Netrin-1 might predict DGF development (training area under the
      receiver operating curve=0.89, cross-validated area under the receiver operating
      curve=0.81). CONCLUSIONS: Poor baseline tubular cell quality (defined by a higher
      rate of tubular atrophy) combined with the reduced potential of apoptotic
      survival factors represented by decreased Netrin-1 gene expression were
      associated with delayed kidney graft function.

PMID- 24092383
TI  - Adult social and professional outcomes of pediatric renal transplant recipients.
AB  - BACKGROUND: Little is known about the socioprofessional situation of adult-aged
      kidney-transplanted children. This nationwide French cohort study documented the
      socioprofessional outcomes of adults who underwent kidney transplantation before
      age 16 years between 1985 and 2002. METHODS: Of 890 patients, 624 were eligible
      for a questionnaire and 374 completed it (response rate=60%; men=193 and
      women=181). The data were compared with the French general population using an
      indirect standardization matched for gender, age, and period. RESULTS: The median
      ages were 27.1 years at survey time and 12.3 years at first transplantation. Of
      the participants, 31.1% lived with a partner (vs. 52.2%; P<0.01) and 35.7% lived
      with their parents (vs. 21.0%; P<0.01). When standardized for parental
      educational level, fewer participants had a high-level degree (>=3-year
      university level) and fewer women had a baccalaureate degree. Professional
      occupations were similar to the French general population, but unemployment was
      higher (18.5% vs. 10.4%; P<0.01). Independent predictive factors for poor
      socioprofessional outcome were primary disease severity (onset in infancy or
      hereditary disease), the presence of comorbidities or sensorial disabilities, low
      educational level of the patient or his parents, female gender, and being on
      dialysis after graft failure. CONCLUSIONS: Transplanted children, particularly
      girls and patients with low parental educational levels, require optimized
      educational, psychologic, and social support to reach the educational level of
      their peers. This support should be maintained during adulthood to help them
      integrate into the working population and build a family.

PMID- 24092384
TI  - Augmented renal prostacyclin by intrarenal bicistronic cyclo-oxygenase
      1/prostacyclin synthase gene transfer attenuates renal ischemia-reperfusion
      injury.
AB  - BACKGROUND: We elucidated the protective mechanism of increased prostacyclin
      (PGI2) derived from adenoviral cyclo-oxygenase (COX)-1/prostacyclin synthase
      (PGIS) (Adv-COPI) gene transfer in rat kidneys with ischemia-reperfusion (I/R)
      injury. METHODS: We tended to augment PGI2 production by intrarenal arterial Adv
      COPI administration with renal venous clamping in female Wistar rats. After Adv
      COPI transfection, we evaluated the renal COX-1 and PGIS protein expression and
      PGI2 and prostaglandin E2 (PGE2) levels in the kidney and renal venous plasma. We
      evaluated the protective effect of PGI2 on hypoxia/reoxygenation-induced tubular
      cells injury or I/R kidneys by measuring oxidative stress, necrosis, apoptosis,
      and autophagy in tubules and kidneys and determining renal function,
      microcirculation, and accumulation of tubular 4-hydroxynonenal in the kidney in
      vivo. RESULTS: Adv-COPI treatment selectively augmented COX-1 and PGIS protein
      expression in the renal proximal and distal tubules and significantly increased
      PGI2, not PGE2, production in the renal venous plasma and kidney at the baseline
      level. I/R markedly depressed renal blood flow and increased the production in
      O2, PGE2, the expression in P47 and Rac-1 expression of two nicotinamide adenine
      dinucleotide phosphate oxidase subunits, cytosolic cytochrome C release,
      proapoptotic marker lamin expression, the pathologic appearance of necrosis,
      apoptosis, and autophagy, and blood urea nitrogen and creatinine levels in the
      damaged kidneys. Adv-COPI protected distal and proximal tubules against
      hypoxia/reoxygenation-enhanced oxidative stress and autophagic, apoptotic, and
      necrotic cell death. Adv-COPI significantly improved renal function by restoring
      renal blood flow, reducing nicotinamide adenine dinucleotide phosphate oxidase
      derived and mitochondria-derived oxidative stress, and necrosis, apoptosis, and
      autophagy. CONCLUSIONS: Increased PGI2 by Adv-COPI protects the kidney against
      I/R-induced oxidative stress, necrosis, apoptosis and autophagy.

PMID- 24092385
TI  - Cardiac response to early conversion from calcineurin inhibitor to everolimus in
      renal transplant recipients: an echocardiographic substudy of the randomized
      controlled CENTRAL trial.
AB  - BACKGROUND: Calcineurin inhibitors are associated with adverse cardiac effects.
      Mammalian target of rapamycin inhibitors have been reported to have beneficial
      effects on cardiac function. We used advanced echocardiographic techniques in a
      randomized controlled trial to examine cardiac responses to an everolimus-based
      arm versus a calcineurin inhibitor-based arm in de novo kidney transplant
      recipients. METHODS: This was a substudy of the Certican Nordic Trial in Renal
      Transplantation study, a randomized controlled trial on safety and efficacy of
      early (week 7 after renal transplantation) conversion from cyclosporine A (CsA)
      to everolimus versus continued CsA during 1-year follow-up. A total of 44
      patients (66% men; median [range] age, 61 [28-78] years) were included. All
      participants had a complete echocardiographic evaluation at baseline and at 1
      year follow-up. RESULTS: Left ventricular (LV) systolic function, LV mass, left
      atrial volumes, and blood pressure response did not differ between groups during
      1-year follow-up. There was, however, a difference between the groups in change
      in peak early mitral velocity after 1 year (P=0.02), and E/e' ratio trended
      higher in the everolimus group (P=0.09). CONCLUSIONS: Early conversion from CsA
      based to everolimus-based immunosuppressive treatment in de novo renal transplant
      recipients caused marginal changes in LV diastolic function but no effect on LV
      systolic function or LV mass.

PMID- 24092386
TI  - Cardiotrophin-1 administration protects from ischemia-reperfusion renal injury
      and inflammation.
AB  - BACKGROUND: Ischemia-reperfusion injury (IRI) remains a major problem in renal
      transplantation, and the inflammatory response to IRI exacerbates the resultant
      renal injury. We have investigated whether the systemic administration of
      cardiotrophin-1 (CT-1) is able to improve renal function and to decrease
      inflammatory responses in a rat model of renal IRI. METHODS: IRI was induced by
      renal pedicle clamping (60 min) followed by reperfusion and contralateral
      nephrectomy. CT-1 was injected through the penile vein 30 min before clamping
      release and its effects were compared with a saline-treated group at five
      different time points of reperfusion. RESULTS: Survival in the CT-1-treated group
      was higher than in the untreated group and prevented IRI-induced reduction in the
      glomerular filtration rate, as shown by blunted increases in creatinine and urea
      plasma levels and less severe decrease in creatinine clearance. These effects of
      CT-1 seem to be mediated by reduction in oxygen-radical production, increased
      superoxide dismutase expression, attenuation of neutrophil and macrophage
      infiltration, lower adhesion molecule expression, lower inflammation demonstrated
      by a decrease of plasma levels of proinflammatory cytokine secretion such as
      tumor necrosis factor-alpha, interleukin-1beta and interferon-gamma, lower
      inducible nitric oxide synthase expression and lower nuclear factor-kappaB
      activation, and reduced apoptosis. CONCLUSIONS: Therefore, these results suggest
      that CT-1 administration prevents IRI and it might be used as a therapeutic
      strategy to protect the kidney against IRI.

PMID- 24092382
TI  - Regulatory myeloid cells in transplantation.
AB  - Regulatory myeloid cells (RMC) are emerging as novel targets for
      immunosuppressive (IS) agents and hold considerable promise as cellular
      therapeutic agents. Herein, we discuss the ability of regulatory macrophages,
      regulatory dendritic cells, and myeloid-derived suppressor cells to regulate
      alloimmunity, their potential as cellular therapeutic agents, and the IS agents
      that target their function. We consider protocols for the generation of RMC and
      the selection of donor- or recipient-derived cells for adoptive cell therapy.
      Additionally, the issues of cell trafficking and antigen (Ag) specificity after
      RMC transfer are discussed. Improved understanding of the immunobiology of these
      cells has increased the possibility of moving RMC into the clinic to reduce the
      burden of current IS agents and to promote Ag-specific tolerance. In the second
      half of this review, we discuss the influence of established and experimental IS
      agents on myeloid cell populations. IS agents believed historically to act
      primarily on T cell activation and proliferation are emerging as important
      regulators of RMC function. Better insights into the influence of IS agents on
      RMC will enhance our ability to develop cell therapy protocols to promote the
      function of these cells. Moreover, novel IS agents may be designed to target RMC
      in situ to promote Ag-specific immune regulation in transplantation and to usher
      in a new era of immune modulation exploiting cells of myeloid origin. 

PMID- 24092387
TI  - Short-term prognosis of living-donor kidney transplantation from hypertensive
      donors with high-normal albuminuria.
AB  - BACKGROUND: High-normal albuminuria (HNA) is an independent predictor of
      cardiovascular risk in the general population. Although hypertensive donor (HTD)
      candidates with HNA were considered acceptable donors by the Amsterdam Forum
      2004, the transplant prognosis of HTDs with HNA has not been determined.
      Therefore, we investigated the transplant prognosis of HTDs with HNA. METHODS: We
      retrospectively analyzed 52 adult living-donor kidney transplants performed at
      Kagawa University Hospital. HNA was defined as albuminuria of 15 to 30 mg/g Cr.
      Changes in kidney function of donors and recipients were assessed up to 2 years
      after transplantation. RESULTS: Overall, 38 donors were normotensive and 14 were
      hypertensive. Nine of 14 HTDs exhibited HNA before donation. More HTDs with HNA
      had arteriosclerotic vasculopathy or glomerulosclerosis than did normotensive
      donors (NTDs). Hypertension and the degree of albuminuria did not affect the
      donors' posttransplantation kidney function. The risk of discompensatory changes
      in kidney function after donation was significantly higher in HTDs with HNA than
      in NTDs (odds ratio, 10.5; 95% confidence interval, 1.51-72.9; P=0.02). In
      multivariate analysis, the coexistence of hypertension and HNA was not
      significantly associated with discompensatory changes after donation (adjusted
      odds ratio, 6.04; 95% confidence interval, 0.19-192; P=0.31). Recipients of HTDs
      with HNA had similar allograft survival rates but lower allograft function
      compared with recipients of NTDs. CONCLUSIONS: Although further studies are
      needed to confirm our results, the short-term prognosis of living-donor kidney
      transplantation was similar between HTDs with HNA and NTDs.

PMID- 24092388
TI  - Toxoplasma gondii exposure in the heart transplant recipient: good, bad, or
      indifferent?

PMID- 24092389
TI  - Tumor-associated neutrophils (TAN) develop pro-tumorigenic properties during
      tumor progression.
AB  - The role and characteristics of tumor-associated neutrophils (TAN) in cancer are
      poorly defined. We have recently shown that TAN can have anti-tumorigenic (N1) or
      pro-tumorigenic (N2) functions. An interesting unanswered question is how the
      phenotype of TAN is influenced by the ongoing evolvement of tumor
      microenvironment. We therefore studied the phenotype and effects of TAN at
      different time points during tumor progression. We used two models of murine
      tumor cancer cell lines-Lewis lung carcinoma (LLC) and AB12 (mesothelioma).
      Neutrophils were studied at early and late stages and compared to each other and
      to neutrophils from bone marrow/periphery of naive mice. Although there was no
      difference in the number of neutrophils entering the tumor, we found that at
      early stages of tumor development, neutrophils were almost exclusively at the
      periphery of the tumor. Only at later stages, neutrophils were also found
      scattered among the tumor cells. We further found that TAN from early tumors are
      more cytotoxic toward tumor cells and produce higher levels of TNF-alpha, NO and
      H2O2. In established tumors, these functions are down-regulated and TAN acquire a
      more pro-tumorigenic phenotype. In line with this phenotype, only depletion of
      neutrophils at later stages of tumor development inhibited tumor growth, possibly
      due to their central location in the tumor. Our work adds another important layer
      to the understanding of neutrophils in cancer by further characterizing the
      changes in TAN during time. Additional research on the functional role of TAN and
      differences between subsets of TAN is currently underway. 

PMID- 24092390
TI  - Supracricoid partial laryngectomy for primary and recurrent laryngeal cancer.
AB  - IMPORTANCE: Supracricoid partial laryngectomy (SCPL) is an essential technique in
      the armamentarium of modern laryngeal organ preservation surgery. OBJECTIVE,
      DESIGN, SETTING: Retrospective case series to review the oncologic outcomes
      following SCPL in a large US-based cohort treated by a single surgeon in a
      tertiary-care university hospital. PARTICIPANTS: A total of 96 consecutive
      patients with primary or recurrent squamous cell carcinoma of the larynx
      undergoing SCPL from 1992 to 2010. INTERVENTIONS: Supracricoid partial
      laryngectomy surgery. MAIN OUTCOMES AND MEASURES: Five-year local control and
      laryngeal preservation, using the Kaplan-Meier method. RESULTS: There were 54
      primary laryngeal carcinomas and 42 previously treated with radiation to the
      larynx; 23% were supraglottic or transglottic tumors (n = 22). The overall 5-year
      local control rate for the series was 94%. For T2 and T3 primary tumors, the 5
      year local control was 100% and 96%, respectively. In patients previously treated
      with radiation, the 5-year local control was 89%, with an 89% laryngeal
      preservation rate. Among stage III or IV primary laryngeal tumors for which
      concurrent chemoradiation was a treatment alternative, the 5-year local and
      locoregional control was 96% and 83%, respectively, and the 5-year larynx
      preservation was 91%. Ultimate local control was achieved for all patients in the
      series. A significant postoperative complication occurred in 19% (n = 18) and 1
      anesthesia-related perioperative death occurred. No total laryngectomies were
      performed for laryngeal dysfunction. CONCLUSIONS AND RELEVANCE: This series
      demonstrates excellent local control for both primary and recurrent laryngeal
      cancers, with functional larynx preservation. In appropriately staged and
      selected patients with T2 or T3 primary laryngeal cancer or laryngeal cancer
      following prior radiation treatment, SCPL should be considered as a treatment
      alternative to non-surgical treatment or total laryngectomy.

PMID- 24092391
TI  - Thermodynamics of native point defects in alpha-Fe2O3: an ab initio study.
AB  - The native point defects in Fe2O3 are theoretically investigated using ab initio
      methods based on the GGA + U formalism. We consider vacancies and interstitials
      of Fe and O atoms as well as the electron polaron as Fe(II) defects at the host
      Fe(III) site. The formation energies and charge transition levels are computed
      for each defect type with careful elimination of size effects of the supercell.
      It is found that the Fe interstitial and vacancy form donor and acceptor levels
      close to band edges, respectively, thereby allowing for charge carriers at room
      temperature. We determine the oxygen deficiency under high-temperature
      equilibrium conditions and find an excellent agreement with experiment. In the
      quenched condition, it is found that the Fermi level is pinned at ~0.5 eV below
      the conduction band minimum, which may limit the performance of Fe2O3 as a
      photoanode in solar water-splitting cells. Furthermore, the oxygen vacancy is
      mostly neutral and the Fe interstitial is responsible for electron carriers.

PMID- 24092392
TI  - High-level soluble expression of one model olfactory receptor (ODR-10) in
      Escherichia coli cell-free system.
AB  - High-level production of G protein-coupled receptors (GPCRs) is usually difficult
      to achieve in heterologous cell systems. The inherent hydrophobicity of these
      receptors could cause aggregation and possible cytotoxicity. Cell-free (CF)
      expression has become a highly promising tool for the fast and efficient
      production of integral membrane proteins. Here we reported the CF production of
      an olfactory receptor from Caenorhabditis elegans, odorant response abnormal
      protein 10 (ODR-10), a member of GPCRs, using the Escherichia coli extracts.
      Different expression vectors were investigated and 175 MUg/ml total ODR-10 was
      achieved with pIVEX2.4c. To obtain soluble ODR-10, different detergents and
      liposome with varied concentrations were respectively added into the CF system.
      High-level expression of soluble ODR-10 (150 MUg/ml) was attained with the
      addition of 1.5 % polyoxyethylene-(20)-cetyl-ether (Brij58) into the CF system.
      Furthermore, the yield of total ODR-10 was improved to 350 MUg/ml by
      supplementing liposomes into the CF system, and the maximal concentration of the
      soluble receptor (102 MUg/ml) was achieved in this liposome-assisted CF system.
      Both strategies produced ODR-10 efficiently by using CF system, and the direct
      reconstitution of the in vitro expressed receptor into liposomes will be
      preferred for its potential applications in many areas. 

PMID- 24092393
TI  - UV-C pre-adaptation of Salmonella: effect on cell morphology and membrane fatty
      acids composition.
AB  - The present study was carried out to evaluate the effects of ultraviolet
      radiations (UV-C) on the fatty acids composition of three serovars of Salmonella:
      S. typhimurium, S. hadar and S. zanzibar. Results obtained show that UV-C
      treatment increases significantly (P <= 0.05) the percentage of cyclic fatty
      acids. The atomic force microscopy was used to study the morphology and cell
      surface of irradiated strains. Results show that UV-C rays induce morphological
      changes and alter the bacterial cell surface (presence of grooves and
      irregularities). 

PMID- 24092397
TI  - Multiple criteria and trade-offs in environmental ethics : comment on "ethics of
      species research and preservation" by Rob Irvine.

PMID- 24092398
TI  - Animals on drugs: understanding the role of pharmaceutical companies in the
      animal-industrial complex.
AB  - In this paper I revisit previous critiques that I have made of much, though by no
      means all, bioethical discourse. These pertain to faithfulness to dualistic
      ontology, a taken-for-granted normative anthropocentrism, and the exclusion of a
      consideration of how political economy shapes the conditions for bioethical
      discourse (Twine Medicine, Health Care and Philosophy 8(3):285-295, 2005;
      International Journal of Sociology of Agriculture and Food 16(3):1-18, 2007,
      2010). Part of my argument around bioethical dualist ontology is to critique the
      assumption of a division between the "medical" (human) and "agricultural"
      (nonhuman) and to show various ways in which they are interrelated. I deepen this
      analysis with a focus on transnational pharmaceutical companies, with specific
      attention to their role in enhancing agricultural production through animal drug
      administration. I employ the topical case of antibiotics in order to speak to
      current debates in not only the interdisciplinary field of bioethics but also
      that of animal studies. More generally, the animal-industrial complex (Twine
      Journal for Critical Animal Studies 10(1):12-39, 2012) is underlined as a highly
      relevant bioethical object that deserves more conceptual and empirical attention.

PMID- 24092395
TI  - A novel small molecule HSP90 inhibitor, NXD30001, differentially induces heat
      shock proteins in nervous tissue in culture and in vivo.
AB  - Heat shock proteins (HSPs) are attractive therapeutic targets for
      neurodegenerative diseases, such as amyotrophic lateral sclerosis (ALS),
      characterized by aberrant formation of protein aggregates. Although motor neurons
      have a high threshold for activation of HSP genes, HSP90 inhibitors are effective
      inducers. This study evaluated NXD30001, a novel, small molecule HSP90 inhibitor
      based on the radicicol backbone, for its ability to induce neuronal HSPs and for
      efficacy in an experimental model of ALS based on mutations in superoxide
      dismutase 1 (SOD1). In motor neurons of dissociated murine spinal cord cultures,
      NXD30001-induced expression of HSP70/HSPA1 (iHSP70) and its co-chaperone
      HSP40/DNAJ through activation of HSF1 and exhibited a protective profile against
      SOD1(G93A) similar to geldanamycin, but with less toxicity. Treatment prevented
      protein aggregation, mitochondrial fragmentation, and motor neuron death,
      important features of mutant SOD1 toxicity, but did not effectively prevent
      aberrant intracellular Ca(2+) accumulation. NXD30001 distributed to brain and
      spinal cord of wild-type and SOD1(G93A) transgenic mice following intraperitoneal
      injection; however, unlike in culture, in vivo levels of SOD1 were not reduced.
      NXD30001-induced expression of iHSP70 in skeletal and cardiac muscle and, to a
      lesser extent, in kidney, but not in liver, spinal cord, or brain, with either
      single or repeated administration. NXD30001 is a very useful experimental tool in
      culture, but these data point to the complex nature of HSP gene regulation in
      vivo and the necessity for early evaluation of the efficacy of novel HSP inducers
      in target tissues in vivo.

PMID- 24092399
TI  - Our love for animals.
AB  - Love does not necessarily benefit its object, and cost-free love may damage both
      object and subject. Our love of animals mobilises several distinct human concerns
      and should not be considered always as a virtue or always as a benefit to the
      animals themselves. We need to place this love in its full psychological,
      cultural, and moral context in order to assess what form it ought to take if
      animals are to benefit from it. 

PMID- 24092400
TI  - Public health ethics and a status for pets as person-things : revisiting the
      place of animals in urbanized societies.
AB  - Within the field of medical ethics, discussions related to public health have
      mainly concentrated on issues that are closely tied to research and practice
      involving technologies and professional services, including vaccination,
      screening, and insurance coverage. Broader determinants of population health have
      received less attention, although this situation is rapidly changing. Against
      this backdrop, our specific contribution to the literature on ethics and law vis
      a-vis promoting population health is to open up the ubiquitous presence of pets
      within cities and towns for further discussion. An expanding body of research
      suggests that pet animals are deeply relevant to people's health (negatively and
      positively). Pet bylaws adopted by town and city councils have largely escaped
      notice, yet they are meaningful to consider in relation to everyday practices,
      social norms, and cultural values, and thus in relation to population health.
      Nevertheless, not least because they pivot on defining pets as private property
      belonging to individual people, pet bylaws raise emotionally charged ethical
      issues that have yet to be tackled in any of the health research on pet
      ownership. The literature in moral philosophy on animals is vast, and we do not
      claim to advance this field here. Rather, we pragmatically seek to reconcile
      philosophical objections to pet ownership with both animal welfare and public
      health. In doing so, we foreground theorizations of personhood and property from
      sociocultural anthropology. 

PMID- 24092401
TI  - Compassionate conservation and the ethics of species research and preservation:
      hamsters, black-footed ferrets, and a response to Rob Irvine : comment on "ethics
      of species research and preservation" by Rob Irvine.

PMID- 24092402
TI  - The dying animal.
AB  - The study of animal death is poised to blossom into an exciting new
      interdisciplinary field-and one with profound relevance for bioethics. Areas of
      interest include the biology and evolution of death-related behavior in nonhuman
      animals, as well as human social, psychological, cultural, and moral attitudes
      toward and practices related to animal death. In this paper, I offer a brief
      overview of what we know about death-related behavior in animals. I will then
      sketch some of the bioethical implications of this emerging field of research. 

PMID- 24092403
TI  - Animal abolitionism meets moral abolitionism : cutting the Gordian knot of
      applied ethics.
AB  - The use of other animals for human purposes is as contentious an issue as one is
      likely to find in ethics. And this is so not only because there are both
      passionate defenders and opponents of such use, but also because even among the
      latter there are adamant and diametric differences about the bases of their
      opposition. In both disputes, the approach taken tends to be that of applied
      ethics, by which a position on the issue is derived from a fundamental moral
      commitment. This commitment in turn depends on normative ethics, which
      investigates the various moral theories for the best fit to our moral intuitions.
      Thus it is that the use of animals in biomedical research is typically defended
      by appeal to a utilitarian theory, which legitimates harm to some for the greater
      good of others; while the opposition condemns that use either by appeal to the
      same theory, but disagreeing about the actual efficacy of animal experimentation,
      or by appeal to an alternative theory, such as the right of all sentient beings
      not to be exploited. Unfortunately, the normative issue seems likely never to be
      resolved, hence leaving the applied issue in limbo. The present essay seeks to
      circumvent this impasse by dispensing altogether with any moral claim or
      argument, thereby cutting the Gordian knot of animal ethics with a meta-ethical
      sword. The alternative schema defended is simply to advance relevant
      considerations, whereupon "there is nothing left but to feel." In a word,
      motivation replaces justification. 

PMID- 24092404
TI  - Bad conservation research is unethical conservation research : comment on "ethics
      of species research and preservation" by Rob Irvine.

PMID- 24092405
TI  - Who makes the decisions, especially when it concerns minors?

PMID- 24092406
TI  - Leukocyte depletion during CPB: effects on inflammation and lung function.
AB  - Cardiopulmonary bypass (CPB) is related to inflammatory response and pulmonary
      dysfunction. The aim of this study was to evaluate the effects of CPB leukocyte
      filtration on inflammation and lung function after coronary artery bypass
      grafting (CABG). A prospective randomized study was performed to compare CABG
      patients undergoing CPB leukocyte filtration (n = 9) or standard CPB (n = 11).
      Computed tomography, oxygenation, leukocyte count, hemodynamic data, PaO2/FiO2,
      shunt fraction, interleukins, elastase, and myeloperoxidase were evaluated. Data
      were analyzed using two-factor ANOVA for repeated measurements. The filtered
      group showed lower neutrophil counts up to 50 min of CPB, lower shunt fraction up
      to 6 h after surgery, and lower levels of IL-10 at the end of surgery (p < 0.05).
      There was no statistically significant difference between groups related to other
      parameters. Leukodepletion during CPB results in neutrophil sequestration by a
      short time, decreased IL-10 serum levels, and lower worsening of lung function
      only temporarily.

PMID- 24092407
TI  - Effects of salicylate on the inflammatory genes expression and synaptic
      ultrastructure in the cochlear nucleus of rats.
AB  - Aspirin (salicylate), as a common drug that is frequently used for long-term
      treatment in a clinical setting, has the potential to cause reversible tinnitus.
      However, few reports have examined the inflammatory cytokines expression and
      alteration of synaptic ultrastructure in the cochlear nucleus (CN) in a rat model
      of tinnitus. The tinnitus-like behavior of rats were detected by the gap prepulse
      inhibition of acoustic startle (GPIAS) paradigm. We investigated the expression
      levels of the tumor necrosis factor-alpha (TNF-alpha), interleukin-6 (IL-6), N
      methyl D-aspartate receptor subunit 2A (NR2A) mRNA and protein in the CN and
      compared synapses ultrastructure in the CN of tinnitus rats with normal ones.
      GPIAS showed that rats with long-term administration of salicylate were
      experiencing tinnitus, and the mRNA and protein expression levels of TNF-alpha
      and NR2A were up-regulated in chronic treatment groups, and they returned to
      baseline 14 days after cessation of treatment. Furthermore, compared to normal
      rats, repetitive salicylate-treated rats showed a greater number of presynaptic
      vesicles, thicker and longer postsynaptic densities, increased synaptic interface
      curvature. These data revealed that chronic salicylate administration markedly,
      but reversibly, induces tinnitus possibly via augmentation of the expression of
      TNF-alpha and NR2A and cause changes in synaptic ultrastructure in the CN. Long
      term administration of salicylate causes neural plasticity changes at the CN
      level.

PMID- 24092408
TI  - Role of the aryl hydrocarbon receptor in the pathogenesis of chronic
      rhinosinusitis with nasal polyps.
AB  - A predominant Th17 population is a marker of chronic rhinosinusitis with nasal
      polyps (CRSwNP) in Chinese patients. As a ligand-activated transcription factor,
      the aryl hydrocarbon receptor (AhR) plays a vital role in promoting or inhibiting
      specific Th cell development. However, its role in CRSwNP remains to be defined.
      The aim of the present study was to investigate whether AhR, which regulates Th17
      cell differentiation, played a role in the pathogenesis of CRSwNP by evaluating
      AhR expression in nasal polyps and peripheral blood mononuclear cells (PBMCs)
      obtained from CRSwNP patients. Forty-eight patients (atopic, 24; non-atopic, 24)
      and 13 controls were studied. To explore the role of AhR in CRSwNP, we analyzed
      the expression of AhR, retinoid-related orphan receptor C (RORC), interleukin
      (IL)-17, and IL-10 and the differentiation of Th17 using mRNA or protein
      detection methods. Notably, the expression of AhR was reduced in CRSwNP, and the
      expression of AhR was lower in the atopic group than in the non-atopic group.
      However, there was a very low level of Th17 and its associated factors (RORC, IL
      17) in the control group compared to the two CRSwNP groups. In particular, the
      polarization of Th17 cells in atopic CRSwNP patients was increased compared with
      non-atopic individuals. In addition, ITE intervention in PBMCs promoted AhR
      expression and attenuated Th17 responses, demonstrating that AhR was more likely
      to suppress Th17 cells differentiation in Chinese CRSwNP patients. This
      information is valuable for obtaining a clear understanding of the pathogenesis
      of CRSwNP. Moreover, patients with atopic CRSwNP may exhibit reduced expression
      of AhR, leading to aggravation of the disproportionate distribution of Th17 cells
      in polyp tissues and PBMCs, thereby suggesting that atopic CRSwNP has a distinct
      pathogenesis from that of non-atopic CRSwNP. 

PMID- 24092410
TI  - [Cancer screening in occupational health: detection or distraction?].

PMID- 24092409
TI  - A new protein-protein interaction sensor based on tripartite split-GFP
      association.
AB  - Monitoring protein-protein interactions in living cells is key to unraveling
      their roles in numerous cellular processes and various diseases. Previously
      described split-GFP based sensors suffer from poor folding and/or self-assembly
      background fluorescence. Here, we have engineered a micro-tagging system to
      monitor protein-protein interactions in vivo and in vitro. The assay is based on
      tripartite association between two twenty amino-acids long GFP tags, GFP10 and
      GFP11, fused to interacting protein partners, and the complementary GFP1-9
      detector. When proteins interact, GFP10 and GFP11 self-associate with GFP1-9 to
      reconstitute a functional GFP. Using coiled-coils and FRB/FKBP12 model systems we
      characterize the sensor in vitro and in Escherichia coli. We extend the studies
      to mammalian cells and examine the FK-506 inhibition of the rapamycin-induced
      association of FRB/FKBP12. The small size of these tags and their minimal effect
      on fusion protein behavior and solubility should enable new experiments for
      monitoring protein-protein association by fluorescence.

PMID- 24092411
TI  - [Biological exposure-related injuries in workers in a health system of the health
      service of Galicia, Spain].
AB  - OBJECTIVE: The objective of this study was to describe the factors involved in
      biological exposure-related injuries occurring in worker from a health system in
      Galicia, Spain. METHODS: The study was conducted in a health system of the Health
      Service of Galicia, that included four hospitals and 72 primary care centers,
      with nearly 6000 workers. The study used occupational injury data available o in
      the injury registry of the Health Service of Galicia for the year 2011. We
      identified 194 biohazard-related injuries. Exposures, locations, devices, tasks
      and causes of these incidents were analysed. RESULTS: The majority of biological
      exposures occurred through needlestick injuries (82%). The areas where more
      injuries occurred were in inpatient wards (37%) and operating rooms (25%). The
      devices most frequently involved were suture needles (15%) and insulin needles
      (15%). The most frequently recorded causes were lack of training and information,
      together with lack of biosafety devices. CONCLUSIONS: Worker training and
      information should be promoted along with the implementation of biosafety
      devices, as the latter measure alone does not seem sufficient to reduce the
      number of injuries.

PMID- 24092412
TI  - [When the doctor becomes a patient: physician health in university hospitals in
      Alicante, Spain].
AB  - OBJECTIVE: To describe health indicators and health determinants in a sample of
      hospital physicians. METHODS: Cross-sectional descriptive survey carried out
      between July 2010 and July 2011. The population of interest were physicians
      employed at the hospitals of Alicante, Elche and Sant Joan d'Alacant. This was a
      convenience sample from which we obtained 281 valid questionnaires (18.8% of the
      population). Study variables included perceived health status, lifestyle, working
      conditions and illness behavior. Frequencies and distributions of these variables
      were calculated. RESULTS: Overall, self-perceived health in our sample of doctors
      was good. Forty percent reported having a chronic illness and 64% self-medicated.
      Only 43% had seen their primary care physician since becoming physicians and 50%
      relied on informal "curbside" medical consultations. Less than 35% had undergone
      preventive exams. Most stated their work is never monotonous and described it as
      stressful and satisfactory. They also felt their work affected their health and
      generated stress and sleep disturbances. CONCLUSIONS: In this study, physician
      behavior with respect to illness was characterized by autonomy, informality and
      difficulty in assuming a sick role. Their preventive habits are insufficient.
      They consider that medical practice affects their health, generating stress and
      sleep disturbances.

PMID- 24092413
TI  - [Functional dysphonia and vocal cord nodules in teachers in Navarra, Spain].
AB  - OBJECTIVE: To describe teachers treated for dysphonia and vocal cord nodules by
      the public health system in Navarra (Spain), to describe associated factors and
      to identify the proportion of these cases registered as occupational diseases.
      METHODS: Cases of dysphonia occurring in persons between the age of 18 and 65
      years, registered between May 2010 and June 2011, and treated in a specific unit
      (Speech Unit) of Otorhinolaryngology Services were identified. Information on
      occupation, sex and clinical diagnosis was collected. For teachers, additional
      information was obtained on smoking habits, teaching level and prior training in
      speech disorders and their prevention. Cases declared as occupational diseases
      were identified from the official Register of Occupational Diseases of Navarra.
      RESULTS: 135 teachers (18% of all dysphonia patients in the sample) were treated
      for dysphonia in the Speech Unit (87% women). Being female was 3-fold higher
      among teachers than other occupations (crude prevalence odds ratio = 3.5; 95%
      confidence interval, 95%CI, 2.1-5.9). Female teachers were also 6.5 years (95%CI,
      1.7-11.4) younger than male teachers. No association was found between smoking
      and risk of vocal cord nodules or dysphonia. Only 20% of teachers treated had
      received training on speech disorders and their prevention. Nine out of 83 cases
      of vocal cord nodules diagnosed in professional voice users were officially
      declared as occupational diseases; in all cases, these were teachers.
      CONCLUSIONS: Dysphonia in teachers is a frequent reason for visiting a specialty
      clinic. Among these professionals, women showed a higher risk of suffering from
      vocal cord nodules. Most cases of vocal cord nodules in our sample were not
      reported as occupational diseases.

PMID- 24092414
TI  - Enhancing shape selectivity without loss of activity--novel mesostructured ZSM5
      catalysts for methylation of toluene to p-xylene.
AB  - An increase in p-xylene selectivity was observed without losing the catalytic
      activity over novel mesoporous nano-sized ZSM5 crystals covered with an external
      SiO2 overlayer created by deposition of tetraethyl orthosilicate. 

PMID- 24092415
TI  - A weighted genetic risk score using all known susceptibility variants to estimate
      rheumatoid arthritis risk.
AB  - BACKGROUND: There is currently great interest in the incorporation of genetic
      susceptibility loci into screening models to identify individuals at high risk of
      disease. Here, we present the first risk prediction model including all 46 known
      genetic loci associated with rheumatoid arthritis (RA). METHODS: A weighted
      genetic risk score (wGRS) was created using 45 RA non-human leucocyte antigen
      (HLA) susceptibility loci, imputed amino acids at HLA-DRB1 (11, 71 and 74), HLA
      DPB1 (position 9) HLA-B (position 9) and gender. The wGRS was tested in 11 366 RA
      cases and 15 489 healthy controls. The risk of developing RA was estimated using
      logistic regression by dividing the wGRS into quintiles. The ability of the wGRS
      to discriminate between cases and controls was assessed by receiver operator
      characteristic analysis and discrimination improvement tests. RESULTS:
      Individuals in the highest risk group showed significantly increased odds of
      developing anti-cyclic citrullinated peptide-positive RA compared to the lowest
      risk group (OR 27.13, 95% CI 23.70 to 31.05). The wGRS was validated in an
      independent cohort that showed similar results (area under the curve 0.78, OR
      18.00, 95% CI 13.67 to 23.71). Comparison of the full wGRS with a wGRS in which
      HLA amino acids were replaced by a HLA tag single-nucleotide polymorphism showed
      a significant loss of sensitivity and specificity. CONCLUSIONS: Our study
      suggests that in RA, even when using all known genetic susceptibility variants,
      prediction performance remains modest; while this is insufficiently accurate for
      general population screening, it may prove of more use in targeted studies. Our
      study has also highlighted the importance of including HLA variation in risk
      prediction models.

PMID- 24092416
TI  - Spot PC ratio estimates of 24-hour proteinuria are more unreliable in lupus
      nephritis than in other forms of chronic glomerular disease.

PMID- 24092418
TI  - Classification criteria for Sjogren's syndrome: nothing ever stands still!

PMID- 24092417
TI  - Update on the safety profile of certolizumab pegol in rheumatoid arthritis: an
      integrated analysis from clinical trials.
AB  - OBJECTIVE: To report the long-term safety data of certolizumab pegol (CZP) in
      rheumatoid arthritis (RA) accumulated as of 30 November 2011. DESIGN: Data from
      10 completed randomised controlled trials (RCT) of CZP in RA and several open
      label extensions (OLE) were pooled across all doses. Reported adverse events (AE)
      occurred between the first dose and 84 days after the last dose. All deaths,
      serious infectious events (SIE) and malignancies were reviewed by external
      experts, classified according to predefined rules, and validated by an external
      steering committee. Incidence rates (IR) and event rates (ER) per 100 patient
      years (PY) are presented. RESULTS: 4049 RA patients who received CZP were
      included in the safety pooling; total exposure 9277 PY, mean exposure 2.1 years
      (range 0.04-7.6). SIE, most frequently pneumonia (IR 0.73/100 PY), were the most
      common serious AE, occurring more frequently in CZP compared to placebo-treated
      patients in RCT (IR 5.61/100 PY vs 1.35/100 PY, odds ratio (OR) 4.35, 95% CI 0.65
      to 29.30). SIE rates were lower in the CZP-treated population including OLE (ER
      4.33/100 PY). 44 patients developed tuberculosis (IR 0.47/100 PY), 39 from high
      endemic regions. 58 deaths occurred in CZP-exposed patients (IR 0.63/100 PY) and
      70 developed malignancies excluding non-melanoma skin cancer (IR 0.76/100 PY),
      including five lymphomas (IR 0.05/100 PY). CONCLUSIONS: No new or unexpected
      safety signals associated with CZP emerged in this updated long-term safety
      analysis. While SIE rates were higher for CZP than for placebo in RCT, the rate
      decreased with continued exposure to CZP. These rates are consistent with data
      previously reported for CZP and other tumour necrosis factor inhibitors.

PMID- 24092419
TI  - Tumour necrosis factor blocking agents and progression of subclinical
      atherosclerosis in patients with ankylosing spondylitis.
AB  - BACKGROUND: Ankylosing spondylitis (AS) is associated with an increased
      cardiovascular risk that might be due to the chronic underlying inflammatory
      process. We investigated whether subclinical atherosclerosis of the carotid
      artery in patients with AS was reduced after anti-inflammatory treatment with
      tumour necrosis factor (TNF) inhibitors in a prospective observational cohort
      study. METHODS: 67 out of 81 AS patients who used TNF inhibitors and underwent
      ultrasonography at baseline returned for follow-up after 4.9 years. Of all
      patients, 12 (15%) discontinued the use of TNF inhibitors. Assessments of
      medication use, AS-related factors and cardiovascular risk factors were measured
      at baseline and repeated at follow-up. B-mode carotid ultrasonography was used to
      investigate arterial wall parameters, including carotid intima-media thickness
      (cIMT) and Young's elastic modulus (YEM). RESULTS: After a median 4.9 years of
      follow-up, cIMT did not change significantly (paired t test +0.011 mm, p=0.561)
      in those who continued the use of TNF inhibitors, while cIMT increased
      substantially (+0.057 mm, p=0.069) in those who did not continue their use of TNF
      inhibitors. The effect of TNF inhibitors was mainly mediated by a subsequent
      decrease in AS disease activity. Vascular elasticity (as measured with YEM) did
      not change significantly in patients who discontinued TNF inhibitors or those who
      continued TNF inhibitors. CONCLUSIONS: The use of TNF inhibitors might stabilise
      or slow down the progression of subclinical atherosclerosis in AS patients,
      reflecting a decreased cardiovascular risk in these patients.

PMID- 24092420
TI  - Cytoskeletal alterations in different developmental stages of in vivo
      cryopreserved preimplantation murine embryos.
AB  - BACKGROUND: This study aimed to investigate the effects of vitrification and slow
      freezing on actin, tubulin, and nuclei of in vivo preimplantation murine embryos
      at various developmental stages using a Confocal Laser Scanning Microscope
      (CLSM). MATERIAL/METHODS: Fifty female mice, aged 4-6 weeks, were used in this
      study. Animals were superovulated, cohabitated overnight, and sacrificed.
      Fallopian tubes were excised and flushed. Embryos at the 2-cell stage were
      collected and cultured to obtain 4- and 8-cell stages before being cryopreserved
      using vitrification and slow freezing. Fixed embryos were stained with
      fluorescence-labelled antibodies against actin and tubulin, as well as DAPI for
      staining the nucleus. Labelled embryos were scanned using CLSM and images were
      analyzed with Q-Win software V3. RESULTS: The fluorescence intensity of both
      vitrified and slow-frozen embryos was significantly lower for tubulin, actin, and
      nucleus as compared to non-cryopreserved embryos (p<0.001). Intensities of
      tubulin, actin, and nucleus in each stage were also decreased in vitrified and
      slow-frozen groups as compared to non-cryopreserved embryos. CONCLUSIONS:
      Cryopreservation of mouse embryos by slow freezing had a more detrimental effect
      on the actin, tubulin, and nucleus structure of the embryos compared to
      vitrification. Vitrification is therefore superior to slow freezing in terms of
      embryonic cryotolerance.

PMID- 24092421
TI  - Mowat-Wilson syndrome: the first report of an association with central nervous
      system tumors.
AB  - Mowat-Wilson syndrome (MWS) is a rare genetic condition where variable and
      multiple congenital anomalies including Hirschsprung's disease, intellectual
      disability, and prominent facial features are present. At molecular level, MWS is
      characterized by many different described mutations in the zinc finger E-box
      protein 2 (ZEB2) gene, ultimately leading to loss of gene function. This report
      is the first to describe the association of MWS with two different asynchronous
      malignant brain tumors (medulloblastoma and glioblastoma) occurring in a child. 

PMID- 24092422
TI  - Pathology in metopic synostosis.
AB  - Premature closure and subsequent ossification of the metopic suture results in
      triangular head shape called trigonocephaly and is characterized by a midline
      metopic ridge, frontotemporal narrowing, and an increased biparietal diameter.
      Trigonocephaly is the second most frequent type of craniosynostosis. It can be
      isolated and associated with other congenital anomalies without any known
      syndrome, or occurs as part of a multiple malformation syndrome. Improvement in
      treatment is directed by a thorough understanding of the basic pathology of this
      condition. This review aims to provide an overview of metopic synostosis by
      correlating what is known about pathogenesis and pathology of this entity. 

PMID- 24092423
TI  - Endoscope-assisted repair of metopic synostosis.
AB  - PURPOSE: Endoscopic treatment of nonsyndromic craniosynostosis has been used in
      recent decades. The aim of this study is to present the results of endoscope
      assisted surgery of the patients with metopic synostosis. METHODS: Nineteen
      patients with metopic synostosis underwent endoscope-assisted surgery between
      2005 and 2012. The frontal angle was measured on CT scans pre- and
      postoperatively. A midline strip craniectomy was made, making sure that the
      removal extended inferiorly to the nasofrontal suture. Postoperatively, all
      patients wear a custom molding helmet. The helmet was then worn for 23 h daily
      and worn for the next 10-12 months. RESULTS: There were 15 boys and 4 girls,
      ranging in age from 4 to 24 weeks. Mean operative time and transfused blood
      volume were 43.42 min and 76.31 ml, respectively. Mean follow-up was 59.3 weeks.
      Good esthetic results, judged by radiological examination and photograph
      comparison, were obtained in all patients. CONCLUSIONS: Endoscope-assisted repair
      of metopic synostosis is safe and offers promising results in infants before the
      age of 6 months. Molding helmet therapy following surgery is very important in
      obtaining the good results. Early diagnosis and referral for surgery are crucial.

PMID- 24092424
TI  - The management of bifocal intracranial germinoma in children.
AB  - OBJECTIVES: Bifocal intracranial germinoma (BFG) is a tumour of the pineal and
      suprasellar regions, which is known to be highly radiosensitive. The definitive
      treatment and outcomes are not well defined, particularly in the paediatric
      population. We review our series of purely paediatric cases from a single
      institution and combine them with the limited reports in the literature to
      determine the results of different management strategies. METHODS: Four patients
      were treated at our institution with a median age of 15.3 years. A literature
      search identified a further 38 paediatric cases with a median age of 12.9 years.
      RESULTS: All four patients had normal serum and CSF tumour markers. One patient
      had a diagnosis made based on imaging findings of bifocal pineal and suprasellar
      lesions presenting with diabetes insipidus. Three others underwent biopsy. All
      had craniospinal radiotherapy, which has led to complete cure with no cases of
      progression at a mean follow-up of 3 years. The most common treatment modality in
      published cases is craniospinal irradiation. In the cases reviewed, limited
      radiation treatments (whole ventricle or focal) combined with chemotherapy
      regimens yield comparable outcomes where there is no spinal dissemination.
      Outcomes do not appear to be altered by biopsy in cases with negative tumour
      markers and characteristic imaging appearances. CONCLUSION: Patients who present
      with a classic appearance of germinoma, negative tumour markers and diabetes
      insipidus probably do not require a biopsy to confirm the diagnosis. No evidence
      of dissemination may obviate the need for craniospinal irradiation, but good
      quality long-term follow-up data are required to demonstrate the benefits of
      combined focal radiotherapy and chemotherapy regimes.

PMID- 24092425
TI  - Anti-EGFR therapy combined with neuromedin B receptor blockade induces the death
      of DAOY medulloblastoma cells.
AB  - PURPOSE: Medulloblastoma is the most common malignant childhood brain tumor for
      which the development of new molecularly targeted therapies is needed. Novel
      therapeutic targets under investigation include growth factor receptors. Here, we
      show that the combined inhibition of the epidermal growth factor receptor (EGFR)
      and neuromedin B receptor (NMBR, BB1) results in increased cell death in human
      medulloblastoma cell lines. METHODS: DAOY and D283 human medulloblastoma cells
      were treated with human recombinant neuromedin B (NMB, an NMBR agonist), the NMBR
      antagonist BIM-23127, the anti-EGFR monoclonal antibody cetuximab, or BIM-23127
      combined with cetuximab. Cell death was examined with trypan blue cell counting.
      RESULTS: Both cell lines expressed mRNA for EGFR, NMB, and NMBR detected by
      reverse transcriptase polymerase chain reaction. Cetuximab at 10 MUg/ml
      significantly reduced the number of DAOY cells, but did not affect D283 cells.
      NMB and BIM-23127 did not change cell number when used alone. However, cetuximab,
      at a dose that did not have an effect by itself, was able to reduce the number of
      DAOY cells when combined with BIM-23127. CONCLUSION: These results provide
      preliminary evidence that NMBR blockade can potentiate the antitumor effect of
      anti-EGFR therapy in medulloblastoma.

PMID- 24092426
TI  - Putting category learning in order: Category structure and temporal arrangement
      affect the benefit of interleaved over blocked study.
AB  - Recent research in inductive category learning has demonstrated that interleaved
      study of category exemplars results in better performance than does studying each
      category in separate blocks. However, the questions of how the category structure
      influences this advantage and how simultaneous presentation interacts with the
      advantage are open issues. In this article, we present three experiments. The
      first experiment indicates that the advantage of interleaved over blocked study
      is modulated by the structure of the categories being studied. More specifically,
      interleaved study results in better generalization for categories with high
      within- and between-category similarity, whereas blocked presentation results in
      better generalization for categories with low within- and between-category
      similarity. In Experiment 2, we present evidence that when presented
      simultaneously, between-category comparisons (interleaved presentation) result in
      a performance advantage for high-similarity categories, but no differences were
      found for low-similarity categories. In Experiment 3, we directly compared
      simultaneous and successive presentation of low-similarity categories. We again
      found an overall benefit for blocked study with these categories. Overall, these
      results are consistent with the proposal that interleaving emphasizes differences
      between categories, whereas blocking emphasizes the discovery of commonalities
      among objects within the same category. 

PMID- 24092427
TI  - Young women's constructions of the HPV vaccine: a cross-cultural, qualitative
      study in Scotland, Spain, Serbia and Bulgaria.
AB  - BACKGROUND: Following international trends, the HPV (human papilloma virus)
      vaccine was introduced in Europe for protection against infection from common
      strands of the HPV virus which can lead to cervical cancer. Young women aged 18
      26 years are at greatest risk of infection by the HPV virus yet have been
      neglected in research, policy, and practice. PURPOSE: To explore young women's
      constructions of the HPV vaccine in four European countries with different
      implementation policies ranging from national school-based programmes, regarded
      as the gold standard, to regional on-demand and private provision. METHOD:
      Qualitative methods comprising 11 focus group discussions with 54 young women
      aged 18-26, in Scotland (n = 10), Spain (n = 25), Serbia (n = 9) and Bulgaria (n
      = 10). A discursive analysis was conducted, following an initial thematic
      analysis. RESULTS: Two competing discursive constructions were considered: the
      'responsible young woman' discourse was constructed as someone with individual
      rights to health, choice and discretion along with responsibilities to protect
      health and make rational decisions. In 'the HPV vaccine: a discourse of
      exclusion', access to the vaccine, wider health promotion and knowledge was
      controlled by others which had the potential to undermine the young woman's
      health. We consider how young women managed this tension through recourse to
      being health vigilant. CONCLUSION: Qualitative, cross-cultural research
      highlighted common concerns amongst young European women towards being
      responsible citizens in the face of their health and highlighted socio-cultural
      constraints to knowledge and resources. We highlight cross-cultural implications
      particularly between Western and Eastern European contexts.

PMID- 24092428
TI  - In vitro invasion assay using matrigelTM: a reconstituted basement membrane
      preparation.
AB  - Basement membranes, specialized extracellular matrices composed of collagens,
      laminins, and proteoglycans, form thin, continuous sheetlike structures that
      separate epithelial tissues from adjacent connective tissues. The crossing of
      basement membranes by cancer cells is a crucial aspect of metastasis-it must
      occur in order that cancer cells can invade lymphatic or blood vessels during
      dissemination and also when they penetrate into the target organ tissue where
      they will eventually colonize to form secondary tumors. The assay system
      described in this chapter utilizes the solubilized basement membrane preparation
      MatrigelTM and measures the ability of cells to attach to the matrix, invade into
      and through the matrix, and migrate towards a chemoattractant. It is technically
      straightforward and requires no specialist equipment and provides a useful tool
      for assessing the invasive ability of cancer cells, exploring the functional role
      of specific cell surface molecules/receptors in this process and screening for
      inhibitors of invasive ability, thus contributing to current knowledge of the
      molecular events occurring during the invasive process. 

PMID- 24092429
TI  - Single cell and spheroid collagen type I invasion assay.
AB  - Tumor invasion is the outcome of a complex interplay between cancer cells and the
      stromal environment and requires the infiltration of a dense, cross-linked
      meshwork of collagen type I extracellular matrix. We use a membrane-free single
      cell and spheroid-based complementary model to study cancer invasion through
      native collagen type I matrices. Cell morphology is preserved during the assays
      allowing real-time monitoring of invasion-induced changes in cell structure and F
      actin organization. Combination of these models with computerized quantification
      permits the calculation of highly reproducible and operator-independent data.
      These assays are versatile in the use of fluorescent probes and have a flexible
      kinetic endpoint. Once the optimal experimental conditions are empirically
      determined, the collagen type I invasion assays can be used for preclinical
      validation of small-molecule inhibitors targeting invasion. Initiation and
      monitoring of the single-cell and spheroid invasion model can be achieved in 8 h
      (over 3 days) and in 14 h (over 5 days), respectively. 

PMID- 24092430
TI  - Rocking adhesion assay system to study adhesion and transendothelial migration of
      cancer cells.
AB  - Adhesion of metastatic cancer cells to the vascular endothelium of the target
      organs and their subsequent transendothelial migration is one of the critical,
      yet poorly understood, steps of the metastatic cascade. Conventionally, the
      mechanisms of this complex process have been studied using static adhesion
      systems or flow assay systems. Static assay systems are easy to set up and
      perform but do not mimic the physiological conditions of blood flow. Flow assays
      closely mimic physiological conditions of flow but are time consuming and require
      specialist equipment. In this chapter we describe the rocking adhesion system
      which incorporates the key advantages of both the static and flow assay systems
      and not only is easy to set up and perform but also mimics conditions of blood
      flow. 

PMID- 24092431
TI  - Small-cell lung cancer (SCLC) cell adhesion on E- and P-selectin under
      physiological flow conditions.
AB  - Hematogenous metastasis is still a poorly understood phenomenon. The rate
      limiting step within the metastatic cascade is not yet clear although it may be
      estimated that the extravasation of circulating tumor cells is a step of crucial
      importance, as most tumor cells that are shed into circulation undergo apoptosis.
      The process of extravasation includes a cascade of consecutive steps, starting
      with adhesion of tumor cells circulating in the bloodstream to endothelial cells,
      mimicking leukocyte adhesion and transmigration. Endothelial cell selectin
      leukocyte glycan interaction occurs when leukocytes adhere to endothelial cells
      under conditions of shear stress. As there are parallels between cancer cell
      endothelial interactions with leukocyte endothelial cell systems an experimental
      setup has been developed in which adhesion of small cell lung carcinoma adhesive
      properties can be analyzed under physiological shear stress conditions during
      their attachment to E- and P-selection. 

PMID- 24092432
TI  - Adhesion of tumor cells to matrices and endothelium.
AB  - Adhesion of tumor cells to matrix components and endothelial cells is essential
      for tumor metastasis. Investigation of the adhesion molecules required and the
      signals which induce tumor cell adhesion and migration are crucial in order to
      increase our understanding of this process. This chapter describes protocols
      which may be used to study tumor cell adhesion to purified matrix elements and
      tissue sections. It also details methods used to investigate cell adhesion to
      endothelial cells, both under static and flow conditions. In addition, there is a
      section detailing the use of endothelial cell cultures on three-dimensional
      collagen gels which are useful when studying adhesion to endothelial cells and
      onward invasion through a protein matrix. 

PMID- 24092433
TI  - Cell aggregation assays.
AB  - Invasion of carcinoma cells is the result of a disequilibrium between invasion
      promoter and invasion suppressor gene products (Mareel and Van Roy, Anticancer
      Res 6:419-435, 1986). The E-cadherin/catenin complex is the most potent invasion
      suppressor at the cell membrane of epithelioid cells (Duffy et al., J Pathol
      214:283-293, 2008). This complex consists of E-cadherin, a transmembrane
      glycoprotein of 120 kDa, which is linked to the actin cytoskeleton via the
      catenins (Behrens et al., J Cell Biol 108:2435-2447, 1989). Downregulation of the
      complex is a common feature in invasive carcinoma cells, and has been recognized
      at several levels, ranging from genomic mutations to functional deficiencies of
      an apparently intact complex (Ozawa et al., Proc Natl Acad Sci USA 87:4246-4250,
      1990). Cell aggregation assays have been set up to test the functionality of the
      complex in epithelioid tumor cells. Functional integrity of the complex is a
      prerequisite for cell-cell adhesion between epithelial cells, and measuring cell
      aggregation in vitro has thus become another elegant tool to study differences
      between invasive and noninvasive cell types. 

PMID- 24092434
TI  - Chick heart invasion assay.
AB  - Tumors are microecosystems in which a continuous cross talk between cancer cells
      and host cells decides on the invasive behavior of the tumor cell population as a
      whole (Mareel et al., Encyclopedia of cancer, San Diego, CA, Academic Press,
      1997). Both compartments secrete activating and inhibitory factors that modulate
      activities such as cell-extracellular matrix (ECM) interaction, cell-cell
      adhesion, remodeling of the ECM, and cell motility. For this reason,
      confrontations of cancer cells with a living normal host tissue in organ culture
      have been introduced by several groups: Wolff and Schneider in France (Wolff and
      Schneider, C R S Soc Biol (Paris) 151:1291-1292, 1957), Easty and Easty in the
      United Kingdom (Easty and Easty, Nature 199:1104-1105, 1963), and Schleich in
      Germany (Schleich et al., J Natl Cancer Inst 56:221-237, 1976). Embryonic chick
      heart fragments in organ culture maintain many histological features of their
      tissue of origin: They are composed of myocytes, fibroblasts, and endothelial
      cells, and their ECM contains fibronectin, laminin, and several collagen types.
      Moreover, the fragments remain contractile, and this activity allows the
      monitoring of their functional integrity during organ culture. 

PMID- 24092435
TI  - Computer simulation of the metastatic progression.
AB  - A novel computer model based on a discrete event simulation procedure describes
      quantitatively the processes underlying the metastatic cascade. Analytical
      functions describe the size of the primary tumor and the metastases, while a rate
      function models the intravasation events of the primary tumor and metastases.
      Events describe the behavior of the malignant cells until the formation of new
      metastases. The results of the computer simulations are in quantitative agreement
      with clinical data determined from a patient with hepatocellular carcinoma in the
      liver. The model provides a more detailed view on the process than a conventional
      mathematical model. In particular, the implications of interventions on
      metastasis formation can be calculated. 

PMID- 24092436
TI  - Theoretical considerations in using animal models of metastasis and brief
      methodology for in vivo colorectal cancer models in SCID and nude mice.
AB  - Metastatic spread is generally responsible for the mortality of colorectal cancer
      patients. There are no adequate treatments for advanced colorectal cancer, and
      novel therapeutic modalities are urgently required. To this end, valid metastatic
      models, which accurately mimic the disease process, are needed. When deciding
      upon a metastasis model, the goals of the investigation will dictate the
      complexity of the model chosen. If biological mechanisms are being investigated,
      only a small number of experimental animals may be required, and a more complex,
      surgically intensive model may be used. If a therapeutic agent is being
      evaluated, owing to group sizes required to generate statistically significant
      effects, a less complex, less surgically intensive model may be preferable. The
      latter, however, may encompass only a particular phase of metastasis rather than
      reflecting all aspects of the metastatic cascade. 

PMID- 24092437
TI  - Syngeneic murine metastasis models: B16 melanoma.
AB  - The murine B16 melanoma is one of the most used tumor models, its application
      having been used to determine the mechanisms associated with the metastatic
      process and the development of anticancer therapies. The B16 melanoma was
      originally established by Fidler and collaborators as a tumor line metastasizing
      to the lung. Since that time a variety of cell lines have been derived, in vitro
      or in vivo, having different metastatic behaviors.The methods used to obtain
      artificial metastases to the lung through the intravenous injection of B16
      melanoma cells and spontaneous metastasis formation following cancer cell growth
      in the footpad are described in this chapter. 

PMID- 24092438
TI  - Imageable clinically relevant mouse models of metastasis.
AB  - In the past 10 years, we have developed a new approach to the development of a
      clinically accurate rodent model for human cancer based on our invention of
      surgical orthotopic implantation (SOI). The SOI models have been described in
      approx. 70 publications and in 4 patents.*SOI allows human tumors of all the
      major types of human cancer to reproduce clinical like tumor growth and
      metastasis in the transplanted rodents. The major features of the SOI models are
      reviewed here and also compared to transgenic mouse models of cancer. 

PMID- 24092439
TI  - Imaging metastatic cell trafficking at the cellular level in vivo with
      fluorescent proteins.
AB  - Fluorescent proteins have revolutionized biology, allowing what was formerly
      invisible to be clearly seen. The Nobel Prize in Chemistry was awarded in 2008
      for the discovery and early use of green fluorescent protein (GFP) as a genetic
      reporter. Our laboratory pioneered the use of GFP for in vivo imaging. In this
      chapter we review the developments within our research on subcellular imaging of
      metastatic trafficking of cancer cells carried out in real time in mice. Dual
      color fluorescent cells, with one color fluorescent protein in the nucleus and
      another color fluorescent protein in the cytoplasm, enable real-time nuclear
      cytoplasmic dynamics to be visualized in living cells in vivo as well as in
      vitro. In the dual-color cells, red fluorescent protein (RFP) is expressed in the
      cytoplasm of cancer cells, and GFP is linked to histone H2B and is expressed in
      the nucleus. Nuclear GFP expression enables visualization of nuclear dynamics,
      whereas simultaneous cytoplasmic RFP expression allows visualization of nuclear
      cytoplasmic ratios in addition to simultaneous cell and nuclear shape changes.
      With the use of dual-color fluorescent cells, it is possible to achieve
      subcellular real-time imaging of cancer cell trafficking in live mice.
      Extravasation can also be imaged in real time. Dual-color imaging has shown that
      cytoplasmic processes of cancer cells exit the vessels first, with nuclei
      following along the cytoplasmic projections [Yamauchi et al., Cancer Res 66:4208
      4214, 2006]. Dual-color in vivo cellular imaging was used to visualize cancer
      cell trafficking blood vessels, as well as in the lymphatic systems of the mice.
      The real-time imaging of cancer cell seeding on the lung has now been achieved
      with dual-color cells. Subcellular in vivo imaging confers great promise for
      understanding metastasis at the cellular level in vivo. 

PMID- 24092440
TI  - Ultrasound techniques for the detection of tumors and metastases in small
      animals.
AB  - Small animals are widely used for the identification of new therapeutic targets
      and the evaluation of potential anticancer therapies. To study tumors and
      metastasis in longitudinal studies of tumor progression, fast noninvasive and
      easy-to-handle imaging modalities are required. Here, techniques for the analysis
      of tumors and metastases by ultrasound imaging are described and the potential
      technical pitfalls are discussed. 

PMID- 24092441
TI  - The PFP/RAG2 double-knockout mouse in metastasis research: small-cell lung cancer
      and prostate cancer.
AB  - Patients with small-cell lung cancer (SCLC) and prostate cancer (PCa) as well as
      other solid tumors may have micro- or macro-metastatic spread at an early stage
      of the disease. SCLC and PCa xenograft transfer models in immunodeficient mice
      fail to model this metastatic spread in vivo. In both tumor types the depletion
      of NK cells found in immunodeficient mice results in an increased number of
      spontaneous metastases, mirroring the clinical situation where NK cell activity
      in patients is related to metastatic spread of the disease. As a result NK cell
      activity directly influences treatment options and mortality. Newly developed
      immunodeficient mouse strains lacking functional T- and B-cells (rag2 knockout)
      however presenting functional NK cells (perforin knockout) are superior in
      producing spontaneous metastasis of SCLC and PCa cells compared to the system
      using SCID mice. 

PMID- 24092442
TI  - Ultrasound-guided intracardial injection and in vivo magnetic resonance imaging
      of single cells in mice as a paradigm for hematogenous metastases.
AB  - Magnetic resonance imaging (MRI) has become an important technique for
      noninvasive cell tracking in preclinical research. Following appropriate cell
      labeling MRI can be used to detect larger cell cohorts and also single cells in
      vivo in mice. Cell distribution to different organs such as brain, liver, spleen,
      and kidneys can be visualized, semi-quantified, and followed over time. Thus, the
      fate of single tumor cells and their eventual development to solid metastases
      could be investigated. Mesenchymal stromal cells can be used as a paradigm for
      metastasizing tumor cells. We have demonstrated a strategy for magnetic and
      fluorescent co-labeling of mesenchymal stromal cells (MSC), ultrasound-guided
      intracardial cell injection with efficient systemic cell delivery, and high
      resolution MRI for repetitive visualization of disseminated co-labeled MSC on a
      single-cell level in vivo in mice. Furthermore, the fluorescent labeling of cells
      enabled effective histopathological validation. 

PMID- 24092443
TI  - Magnetic resonance imaging of metastases in xenograft mouse models of cancer.
AB  - Magnetic resonance imaging (MRI) of small animals has emerged as a valuable tool
      to noninvasively monitor tumor growth in mouse models of cancer. However, imaging
      of metastases in mouse models is difficult due to the need for high spatial
      resolution. We have demonstrated MRI of metastases in the liver, brain, adrenal
      glands, and lymph nodes in different xenograft mouse models of cancer. MRI of
      mice was performed with a clinical 3.0 T magnetic resonance scanner and a
      commercially available small-animal receiver coil. The imaging protocol consisted
      of T1- and T2-weighted fat-saturated spin echo sequences with a spatial
      resolution of 200 MUm * 200 MUm * 500 MUm. Total acquisition time was 30 min per
      mouse. The technique allowed for repetitive examinations of larger animal cohorts
      to observe the development of metastases. 

PMID- 24092444
TI  - Spontaneous and experimental metastasis models: nude mice.
AB  - Immunodeficient mice are widely used for cancer research as they can provide an
      in vivo system in which to study the tumorigenicity and metastatic potential of
      human cancer cells. The athymic or "nude" mouse has been employed for a variety
      of experimental analyses of tumor growth, invasion, and metastasis. This chapter
      describes two types of experimental design for studying metastasis in vivo. The
      spontaneous metastasis models assess the ability of cells to disseminate from a
      local tumor, and are commonly initiated by the injection of the cells into an
      organ reflecting the tissue of origin of the cancer (orthotopic injection).
      Models of experimental metastasis evaluate the ability of tumor cells to arrest,
      extravasate, and grow in various organs following intravascular injection. The
      appropriate design of animal models using nude mice, and established human tumor
      cell lines, assists in the generation of novel information about the metastatic
      phenotype, and provides a valuable, preclinical system for testing anti
      metastatic therapies. 

PMID- 24092445
TI  - Identifying the origin and phenotype of cells in tumor xenografts.
AB  - The growth of human tumor cells transplanted into immunodeficient mice is
      frequently studied to gain understanding about the way potential drug treatments
      interfere with growth in vivo. A wide range of methods is available for learning
      about specific aspects of tumor cell behavior, for example, cells may be
      administered to follow their ability to grow close to the site of injection which
      may be at a generic site or one specific to that type of tumor. Some models of
      metastasis follow the appearance of a tumor mass after intravascular
      administration of tumor cells; others score remote growth after removal of a
      primary tumor implanted subcutaneously. Assessing metastatic growth may
      increasingly rely on serial observation of tumor cell numbers as seen by whole
      body imaging, but the sensitivity of these methods is poor in terms of the
      minimum number of cells detectable, and histological follow-up to establish tumor
      cell numbers can be confounded by variable expression or even silencing of
      reporter genes. Here we describe how fluorescence in situ hybridization (FISH)
      using commercially available probes can very easily be used to detect even single
      metastatic tumor cells in mouse models, using routinely fixed and processed
      tissue samples, and without the tumor cell lines needing to express engineered
      reporter genes. The FISH protocol can be combined with other standard
      histological protocols to study the behavior of tumor cells and adjacent host
      cells to improve our understanding of tumor-stroma interactions, and is also
      useful for simultaneous demonstration of the cell of origin and phenotype of
      cells used in regenerative medicine-based applications. 

PMID- 24092446
TI  - Physical training and hypertension have opposite effects on endothelial brain
      derived neurotrophic factor expression.
AB  - AIMS: Changes in circulating brain-derived neurotrophic factor (BDNF) levels were
      reported in patients with or at risk for cardiovascular diseases associated with
      endothelial dysfunction, suggesting a link between BDNF and endothelial
      functionality. However, little is known on cardiovascular BDNF. Our aim was to
      investigate levels/localization, function, and relevance of cardiovascular BDNF.
      METHODS AND RESULTS: BDNF levels (western blotting) and localization
      (immunostaining) were assessed in the heart and aorta from rats with impaired
      (spontaneously hypertensive rats [SHR]), normal (Wistar Kyoto rats [WKY]), and
      improved (SHR and WKY subjected to physical training) endothelial function. BDNF
      levels were also measured in cultured endothelial cells (CECs) subjected to low
      and high shear stress. The cardiovascular effects of BDNF were investigated in
      isolated aortic rings and hearts. The results showed high BDNF levels in the
      heart and aorta, the expression being prominent in endothelial cells as compared
      with other cell types. Exogenous BDNF vasodilated aortic rings but changed
      neither coronary flow nor cardiac contractility. Hypertension was associated with
      decreased expression of BDNF in the endothelium, whereas physical training led to
      endothelial BDNF up-regulation not only in WKY but also in SHR. Exposure of CECs
      to high shear stress stimulated BDNF production and secretion. CONCLUSION:
      Cardiovascular BDNF is mainly localized within endothelial cells in which its
      expression is dependent on endothelial function. These results open new
      perspectives on the role of endothelial BDNF in cardiovascular health.

PMID- 24092447
TI  - Intensity of follow-up after pancreatic cancer resection.
AB  - The prognosis of patients diagnosed with pancreatic adenocarcinoma remains
      dismal. Of the 15-20 % of patients who are candidates for potentially curative
      resection, 66-92 % will develop recurrent disease. Although guidelines for
      surveillance in the postoperative setting exist, they are not evidence based, and
      there is wide variability of strategies utilized. Current surveillance guidelines
      as suggested by the National Comprehensive Cancer Network (NCCN) include routine
      history and physical, measurement of serum cancer-associated antigen 19-9 (CA19
      9) levels, and computed tomographic imaging at 3- to 6-month intervals for the
      first 2 years, and annually thereafter. However, the lack of prospective clinical
      data examining the efficacy of different surveillance strategies has led to a
      variability of the intensity of follow-up and a lack of consensus on its
      necessity and efficacy. Recent therapeutic advances may have the potential to
      significantly alter survival after recurrence, but a careful consideration of
      current surveillance strategies should be undertaken to optimize existing
      approaches in the face of high recurrence and low survival rates.

PMID- 24092448
TI  - Serum omentin levels in patients with obstructive sleep apnea.
AB  - BACKGROUND: Obstructive sleep apnea syndrome (OSAS) is associated with increased
      rates of cardiovascular diseases (CVD). The basic mechanisms involved in the
      increased cardiovascular risk of OSAS remain unclear. Recent discoveries of fat
      secreted substances which serve endocrine roles improve our understanding of the
      relationship between OSAS, CVD, and the metabolic syndrome. In this study, we
      aimed to examine associations between omentin levels and OSA. METHODS: Forty-six
      newly diagnosed OSA patients and 35 non-apneic controls were enrolled in this
      study. Demographical data, cigarette smoking status, previous history of chronic
      diseases including CVD and metabolic diseases and drugs, and habits were obtained
      using a standardized questionnaire. All patients underwent polysomnographic
      evaluation. Omentin was measured the following morning. RESULTS: The mean age was
      48.1 +/- 12.5 (24-74) years in the OSA group and 42.8 +/- 14.1 (21-69) years in
      the control group. Of the 81 patients, 46 (34 males and 12 females) were
      classified as having OSA and 35 patients (20 males and 15 females) as control.
      Plasma levels of omentin were found to be markedly higher in OSA patients (570.8
      ng/ml) than in the control group (432.0 ng/ml; p < 0.001). In addition, plasma
      levels of omentin were found to be high in all OSA subgroups than in controls.
      The plasma omentin levels were significantly correlated only with age in patients
      with OSA. CONCLUSIONS: We conclude that circulating omentin levels are elevated
      in OSA patients. To the best of our knowledge, this is the first clinical study
      that demonstrated the association between omentin and OSA.

PMID- 24092449
TI  - Influence of sleep apnea severity on blood pressure variability of patients with
      hypertension.
AB  - PURPOSE: Obstructive sleep apnea (OSA) is a risk factor for the development of
      hypertension and cardiovascular disease. Apnea overloads the autonomic
      cardiovascular control system and may influence blood pressure variability, a
      risk for vascular damage independent of blood pressure levels. This study
      investigates the hypothesis that blood pressure variability is associated with
      OSA. METHODS: In a cross-sectional study, 107 patients with hypertension
      underwent 24-h ambulatory blood pressure monitoring and level III polysomnography
      to detect sleep apnea. Pressure variability was assessed by the first derivative
      of blood pressure over time, the time rate index, and by the standard deviation
      of blood pressure measurements. The association between the apnea-hypopnea index
      and blood pressure variability was tested by univariate and multivariate methods.
      RESULTS: The 57 patients with apnea were older, had higher blood pressure, and
      had longer duration of hypertension than the 50 patients without apnea. Patients
      with apnea-hypopnea index (AHI) >= 10 had higher blood pressure variability
      assessed by the standard deviation than patients with AHI < 10 during sleep (10.4
      +/- 0.7 versus 8.0 +/- 0.7, P = 0.02) after adjustment for age, body mass, and
      blood pressure. Blood pressure variability assessed by the time rate index
      presented a trend for association during sleep (P = 0.07). Daytime blood pressure
      variability was not associated with the severity of sleep apnea. CONCLUSION:
      Sleep apnea increases nighttime blood pressure variability in patients with
      hypertension and may be another pathway linking sleep abnormalities to
      cardiovascular disease.

PMID- 24092450
TI  - Selection of microalgae and cyanobacteria strains for bicarbonate-based
      integrated carbon capture and algae production system.
AB  - Using microalgae to capture CO2 from flue gas is an ideal way to reduce CO2
      emission, but this is challenged by the high cost of carbon capture and
      transportation. To address this problem, a bicarbonate-based integrated carbon
      capture and algae production system (BICCAPS) has been proposed, in which
      bicarbonate is used for algae culture, and the regenerated carbonate from this
      process can be used to capture more CO2. High-concentration bicarbonate is
      obligate for the BICCAPS. Thus, different strains of microalgae and cyanobacteria
      were tested in this study for their capability to grow in high-concentration
      NaHCO3. The highest NaHCO3 concentrations they are tolerant to were determined as
      0.30 M for Synechocystis sp. PCC6803, 0.60 M for Cyanothece sp., 0.10 M for
      Chlorella sorokiniana, 0.60 M for Dunaliella salina, and 0.30 M for Dunaliella
      viridis and Dunaliella primolecta. In further study, biomass production from
      culture of D. primolecta in an Erlenmeyer flask with either 0.30 M NaHCO3 or 2 %
      CO2 bubbling was compared, and no significant difference was detected. This
      indicates BICCAPS can reach the same biomass productivity as regular CO2 bubbling
      culture, and it is promising for future application.

PMID- 24092451
TI  - Endoglucanase and total cellulase from newly isolated Rhizopus oryzae and
      Trichoderma reesei: production, characterization, and thermal stability.
AB  - A multienzymatic complex production was evaluated, as well as endoglucanase and
      total cellulase characterization, during solid-state fermentation of rice
      industry wastes with Rhizopus oryzae CCT 7560 (newly isolated microorganism) and
      Trichoderma reesei QM 9414 (control). R. oryzae produced enzymes with higher
      activity at 15 h of fermentation (5.1 and 2.3 U g(-1) to endoglucanase and total
      cellulase), while T. reesei produced them at 55 h (15.3 and 2.8 U g(-1) to
      endoglucanase and total cellulase). The optimum temperature for total cellulase
      and endoglucanase was 60  degrees C. For Trichoderma and Rhizopus, the optimum pH
      was 5.0 and 6.0 for total cellulase and 6.0 and 5.0 for endoglucanase,
      respectively. The enzymes produced by Rhizopus presented higher stability at the
      temperature range evaluated (25-100  degrees C); the endoglucanase KM value was
      20 times lower than the one found for Trichoderma. The characterization of the
      cellulolytic enzymes from the fungal species native of rice husk revealed that
      they can be more efficient than the genetically modified enzymes when rice husk
      and rice bran are used as substrates.

PMID- 24092452
TI  - Enzymatic characterization of a type II isocitrate dehydrogenase from pathogenic
      Leptospira interrogans serovar Lai strain 56601.
AB  - Leptospira interrogans, a Gram-negative pathogen, could cause infections in a
      wide variety of mammalian hosts, but due to their fastidious cultivation
      requirements and the lack of genetic systems, the pathogenic factor is still not
      clear. Isocitrate dehydrogenase (IDH) is a key enzyme in the tricarboxylation
      (TCA) cycle, which could have an important impact on the growth and pathogenesis
      of the bacteria. In the present study, we first report the cloning, heterologous
      expression, and detailed characterization of the IDH gene from L. interrogans
      serovar Lai strain 56601(LiIDH). The molecular weight of LiIDH was determined to
      be 87 kDa by filtration chromatography, suggesting LiIDH is a typical homodimer.
      The optimum activity of LiIDH was found at 60  degrees C, and its optimum pH was
      7.0 (Mn(2+)) and 8.0 (Mg(2+)). Heat inactivation studies showed that heat
      treatment for 20 min at 50  degrees C caused a 50 % loss of enzyme activity.
      LiIDH was completely divalent cation dependent as other typical dimeric IDHs and
      Mg(2+) was its best activator. The recombinant LiIDH specificities (kcat/Km
      values for NADP(+) and NAD(+)) in the presence of Mg(2+) and Mn(2+) were 6,269
      fold and 1,000-fold greater for NADP(+) than NAD(+), respectively. This current
      work is expected to shed light on the functions of metabolic enzymes in L.
      interrogans and provide useful information for LiIDH to be considered as a
      possible candidate for serological diagnostics and detection of L. interrogans
      infection.

PMID- 24092453
TI  - Water miscible mono alcohols' effect on the proteolytic performance of Bacillus
      clausii serine alkaline protease.
AB  - In this study, our investigations showed that the increasing concentrations of
      all examined mono alcohols caused a decrease in the Vm, kcat and kcat/Km values
      of Bacillus clausii GMBE 42 serine alkaline protease for casein hydrolysis.
      However, the Km value of the enzyme remained almost the same, which was an
      indicator of non-competitive inhibition. Whereas inhibition by methanol was
      partial non-competitive, inhibition by the rest of the alcohols tested was simple
      non-competitive. The inhibition constants (KI) were in the range of 1.32-3.10 M,
      and the order of the inhibitory effect was 1-propanol>2
      propanol>methanol>ethanol. The DeltaG(?) and DeltaG(?)E-T values of the enzyme
      increased at increasing concentrations of all alcohols examined, but the
      DeltaG(?)ES value of the enzyme remained almost the same. The constant Km and
      DeltaG(?)ES values in the presence and absence of mono alcohols indicated the
      existence of different binding sites for mono alcohols and casein on enzyme the
      molecule. The kcat of the enzyme decreased linearly by increasing log P and
      decreasing dielectric constant (D) values, but the DeltaG(?) and DeltaG(?)E-T
      values of the enzyme increased by increasing log P and decreasing D values of the
      reaction medium containing mono alcohols.

PMID- 24092454
TI  - Calix[n]arene carboxylic acid derivatives as regulators of enzymatic reactions:
      enhanced enantioselectivity in lipase-catalyzed hydrolysis of (R/S)-naproxen
      methyl ester.
AB  - Candida rugosa lipase was immobilized with a sol-gel encapsulation procedure in
      the presence and absence of a calix[n]arene carboxylic acid derivative grafted
      onto magnetic nanoparticles or in the presence of the calix[n]arene carboxylic
      acid derivative with Fe3O4 magnetic nanoparticles as an additive. Through the
      enantioselective hydrolysis of racemic naproxen methyl ester and the hydrolysis
      of p-nitrophenylpalmitate, the relative enzyme activity was evaluated and tested.
      These results show that the encapsulated lipase without supports has lower
      conversion and enantioselectivity compared to the Calix[n]COOH-based encapsulated
      lipase. It has also been observed that the Calix[4]COOH-based encapsulated lipase
      has excellent enantioselectivity (enantiomeric ratio (E) > 400) as compared to
      encapsulated-free lipase enantioselectivity (E = 137), and it also has an
      enantiomeric excess value of ~98 % for S-naproxen.

PMID- 24092455
TI  - Canine parvovirus type 2a (CPV-2a)-induced apoptosis in MDCK involves both
      extrinsic and intrinsic pathways.
AB  - The canine parvovirus type 2 (CPV-2) causes an acute disease in dogs. It has been
      found to induce cell cycle arrest and DNA damage leading to cellular lysis. In
      this paper, we evaluated the apoptotic potential of the "new CPV-2a" in MDCK
      cells and elucidated the mechanism of the induction of apoptosis. The exposure of
      MDCK cells to the virus was found to trigger apoptotic response. Apoptosis was
      confirmed by phosphatidylserine translocation, DNA fragmentation assays, and cell
      cycle analysis. Activation of caspases-3, -8, -9, and -12 and decrease in
      mitochondrial potential in CPV-2a-infected MDCK cells suggested that the CPV-2a
      induced apoptosis is caspase dependent involving extrinsic, intrinsic, and
      endoplasmic reticulum pathways. Increase in p53 and Bax/Bcl2 ratio was also
      observed in CPV-2a-infected cells.

PMID- 24092457
TI  - A tetranuclear Cu4(MU3-OH)2-based metal-organic framework (MOF) with sulfonate
      carboxylate ligands for proton conduction.
AB  - A new tetranuclear Cu4(MU3-OH)2-based metal-organic framework (MOF) with
      sulfonate-carboxylate ligands features large hydrophilic channels. This MOF
      exhibits proton conductivity over 10(-3) S cm(-1) at 85-100  degrees C and 98%
      relative humidity and colossal dielectric constant.

PMID- 24092456
TI  - [Early complication rate of fractures close to the hip joint. Dependence on
      treatment in on-call services and comorbidities].
AB  - BACKGROUND: Guidelines advocate early surgery for proximal femoral fractures so
      that operations are frequently performed in on-call duty times. Multimorbid
      patients also suffer more frequently from postoperative complications. Does on
      call duty or night shift services correlate with higher postoperative
      complication rates and what influence do comorbidities have? PATIENTS AND
      METHODS: In 300 patients (> 65 years) postoperative surgical and non-surgical
      complications were documented and correlated with comorbidities, on-call duty and
      night shift service times. RESULTS: Postoperative complications were observed in
      10.7 % of surgical and 62 % of non-surgical cases. Surgery in on-call duty and
      night shift times did not increase the postoperative complication rate.
      Comorbidities, age and ASA classification correlated with postoperative
      complications which significantly prolonged hospital stay. CONCLUSION: Surgery of
      proximal femoral fractures in on-call duty and night shift times is justified
      because postoperative complications are not increased. Comorbidities and higher
      age correlated with postoperative complications. Postoperative complications
      should be avoided because they result in prolonged hospital stay.

PMID- 24092458
TI  - Visual and anatomical outcomes after silicone oil removal in patients with
      complex retinal detachment.
AB  - To evaluate outcomes of temporary silicone oil (SO) tamponade in patients with
      complex retinal detachment. A retrospective study of 184 eyes of 177 consecutive
      patients who underwent SO removal (SOR) by one surgeon between 2000 and 2010.
      Indications for the use of SO were proliferative vitreoretinopathy (56 eyes),
      difficult rhegmatogenous retinal detachment (RRD) (58 eyes), diabetic traction
      retinal detachment (DTRD) (29 eyes), RRD due to macular hole in highly myopic
      eyes (16 eyes), giant retinal tears (13 eyes), and RRD after penetrating trauma
      (12 eyes). All eyes underwent prophylactic 360 degrees  laser retinopexy and
      encircling buckle at the time of primary surgery. The mean duration of SO
      tamponade was 47 weeks, with a mean follow-up of 66.9 weeks after SOR. Anatomical
      success after SOR was achieved in 96.73 %. Final visual outcome of >=20/200 was
      significantly higher in eyes with RRD compared to eyes with DTRD. Young age (<=16
      years), performance of pars plana lensectomy at primary procedure and presence of
      pseudophakia at last follow-up were factors associated with good visual outcome
      in eyes with RRD. Factors predicting attached retina at last follow-up were older
      age (>16 years), normal intraocular pressure (IOP) at initial presentation and no
      relaxing retinotomy performed during the primary procedure in eyes with RRD.
      Complications were cataract (100 %) in phakic eyes, increased IOP (15.7 %),
      keratopathy (3.8 %), and hypotony (2.1 %). The low redetachment rate after SOR in
      the present study might be due to prophylactic 360 degrees  retinopexy and use of
      encircling buckles at time of primary retinal reattachment.

PMID- 24092459
TI  - Manual small incision cataract surgery for mature cataracts.

PMID- 24092461
TI  - Diffusion analysis with triexponential function in hepatic steatosis.
AB  - Our purpose was to assess the influence of liver steatosis on diffusion by
      triexponential analysis. Thirty-three patients underwent diffusion-weighted
      magnetic resonance imaging with multiple b values for perfusion-related
      diffusion, fast free diffusion, and slow restricted diffusion coefficients (D p,
      D f, D s) and fractions (F p, F f, F s). They also underwent dual-echo gradient
      echo imaging for measurement of the hepatic fat fraction (HFF). Of these, 13
      patients were included in the control group and 20 in the fatty liver group with
      HFF >5 %. The parameters of the two groups were compared by use of the Mann
      Whitney U test. The relationships between diffusion coefficients and HFFs were
      assessed by use of the Pearson correlation. D p and D f were reduced
      significantly in the steatotic liver group compared with those in the control
      group (D p = 27.72 +/- 6.61 * 10(-3) vs. 33.33 +/- 6.47 * 10(-3) mm(2)/s, P =
      0.0072; D f = 1.70 +/- 0.53 * 10(-3) vs. 2.06 +/- 0.40 * 10(-3) mm(2)/s, P =
      0.0224). There were no significant differences in the other parameters between
      the two groups. Furthermore, D p and D f were correlated with HFF (P < 0.0001, r
      = -0.64 and P = 0.0008, r = -0.56, respectively). Decreased liver perfusion in
      steatosis caused the reduction in D p, and extracellular fat accumulation and
      intracellular fat droplets in steatosis led to the reduction in D f. Thus, the
      influence of hepatic steatosis should be taken into consideration when
      triexponential function analysis is used for assessment of diffuse liver disease.

PMID- 24092462
TI  - Discordant cerebral lateralisation for verbal fluency is not an artefact of
      attention: evidence from MzHd twins.
AB  - The current study investigated how the brain structure-function relationships
      between covert and overt verbal fluency in monozygotic handedness discordant
      (MzHd) twins relates to broader attentional measures. Evidence presented here
      shows that the structure-function correlation demonstrated between functional
      cerebral lateralisation and corpus callosum widths 22-39, contiguous with Broca's
      area and the middle frontal gyri (Gurd et al. in Brain Struct Funct 218:491-509,
      2013), is not an artefact of attention. Twenty-five pairs of female MzHd twins
      performed a verbal switching task titrated for number of switches. The paradigm
      permits calculation of switch rates and costs. The switch rate and cost varied as
      a function of number of switches (1, 2, 3). There were no differences in any
      measure in relation to right-left handedness in twin pairs. This was supported by
      large and significant within-twin pair correlations. Atypical functional
      lateralisation of inferior and middle frontal lobes does not appear to be
      associated with better or worse performance on verbal task-switching. Discordant
      lateralisation for verbal fluency does not predict behavioural performance
      profiles in MzHd twins. This evidence is compatible with a view that attentional
      components of verbal fluency task performance may have significant heritable
      components. It does not indicate that neural correlates of frontal cerebral
      laterality for verbal fluency in MzHd twins are significantly accountable for by
      heritable components. 

PMID- 24092463
TI  - A structure-property-performance investigation of perylenediimides as electron
      accepting materials in organic solar cells.
AB  - Solution-processed perylenediimides (PDIs) with varying peri and bay substituents
      are characterized in order to better understand the relationships between
      molecular structure, solid state order, charge transport, and photovoltaic
      performance. It was found that bulky bay substituents interfere with molecular
      packing, leading to low charge transport and photovoltaic efficiencies compared
      to PDIs with fewer or less disruptive substituents. We assessed the potential of
      PDIs as acceptors for organic photovoltaics (OPVs) by utilizing a solution
      processed bilayer OPV device architecture with the donor benzoporphyrin. At
      AM1.5G illumination, power conversion efficiencies (PCEs) up to 2.0% are obtained
      for solution-processed bilayer OPVs employing PDIs as acceptors. These results
      demonstrate the potential of PDIs as photovoltaic acceptor materials while
      elucidating the relationships between molecular structure and material
      properties. 

PMID- 24092460
TI  - Genetic analysis of quantitative phenotypes in AD and MCI: imaging, cognition and
      biomarkers.
AB  - The Genetics Core of the Alzheimer's Disease Neuroimaging Initiative (ADNI),
      formally established in 2009, aims to provide resources and facilitate research
      related to genetic predictors of multidimensional Alzheimer's disease (AD)
      related phenotypes. Here, we provide a systematic review of genetic studies
      published between 2009 and 2012 where either ADNI APOE genotype or genome-wide
      association study (GWAS) data were used. We review and synthesize ADNI genetic
      associations with disease status or quantitative disease endophenotypes including
      structural and functional neuroimaging, fluid biomarker assays, and cognitive
      performance. We also discuss the diverse analytical strategies used in these
      studies, including univariate and multivariate analysis, meta-analysis, pathway
      analysis, and interaction and network analysis. Finally, we perform pathway and
      network enrichment analyses of these ADNI genetic associations to highlight key
      mechanisms that may drive disease onset and trajectory. Major ADNI findings
      included all the top 10 AD genes and several of these (e.g., APOE, BIN1, CLU,
      CR1, and PICALM) were corroborated by ADNI imaging, fluid and cognitive
      phenotypes. ADNI imaging genetics studies discovered novel findings (e.g., FRMD6)
      that were later replicated on different data sets. Several other genes (e.g.,
      APOC1, FTO, GRIN2B, MAGI2, and TOMM40) were associated with multiple ADNI
      phenotypes, warranting further investigation on other data sets. The broad
      availability and wide scope of ADNI genetic and phenotypic data has advanced our
      understanding of the genetic basis of AD and has nominated novel targets for
      future studies employing next-generation sequencing and convergent multi-omics
      approaches, and for clinical drug and biomarker development. 

PMID- 24092464
TI  - Positioning of the ablation catheter in total endoscopic ablation.
AB  - Minimally invasive ablation of atrial fibrillation is an option in patients not
      suitable for or refractory to catheter ablation. Total endoscopic ablation can be
      performed via a monolateral approach, whereby a left atrial box lesion is
      created. If the ablation is introduced from the right side, the positioning of
      the ablation catheter on the partly hidden left pulmonary veins is of vital
      importance. Using thoracoscopy in combination with multiplane transoesophageal
      echocardiography, the anatomical position of the ablation catheter can be
      established. Our experience in over 60 procedures has confirmed this to be a safe
      technique of total endoscopic ablation. 

PMID- 24092465
TI  - A porcine model for acute ischaemic right ventricular dysfunction.
AB  - OBJECTIVES: To establish an experimental model for acute ischaemic isolated right
      ventricular dysfunction and the subsequent haemodynamic changes. METHODS: An open
      chest porcine model with ischaemic dysfunction of the right ventricle induced by
      ligation of the three main branches supporting the right ventricular free wall.
      Invasive monitoring of mean arterial blood pressure (MAP), central venous
      pressure (CVP), left atrial pressure (LAP) and right ventricular pressure (RVP);
      ultrasonic measurement of cardiac output (CO) and calculation of haemodynamic
      parameters such as stroke volume (SV), systemic vascular resistance (SVR),
      pulmonary vascular resistance (PVR) and right ventricular stroke work (RVSW)
      using standard formulae. RESULTS: The ischaemic challenge to the right ventricle
      resulted in a significant (>=30%) reduction in RVSW associated with an increase
      (6-25%) in CVP and reduction (8-18%) in pulmonary artery pressure (PAP) despite
      unchanged PVR, all reflecting the failing right ventricle. There was also a
      significant drop in CO (14-22%) despite unchanged LAP indicating lessened
      transpulmonary delivery of left ventricular preload due to the failing right
      ventricle causing the haemodynamic compromise rather than left ventricular
      failure. Supraventricular and ventricular arrhythmias occurred in three and two
      out of seven pigs, respectively-all of which except one were successfully
      resuscitated with cardioversion and/or defibrillation. CONCLUSIONS: This novel
      open-chest porcine model of induced ischaemia of the right ventricular free wall
      resulted in significant haemodynamic compromise confirmed using standard
      haemodynamic measurements making it useful for further research on acute,
      ischaemic isolated right ventricular failure.

PMID- 24092466
TI  - Apical left ventricular false aneurysm after transapical transcatheter aortic
      valve implantation.
AB  - Transcatheter valve implantation (TAVI) is becoming a routine procedure to treat
      severe symptomatic aortic stenosis. It is associated with complications different
      from those of conventional aortic valve surgery. We describe an 80-year old man
      who developed an apical left ventricular (LV) false aneurysm 3 months after
      transapical TAVI (TA-TAVI) complicated postoperatively by a surgical site
      infection (SSI). Three months earlier, an Edwards Sapien bioprosthesis no. 29 had
      been successfully inserted transapically because of severe comorbidities and a
      very large aortic annulus. His postoperative course was complicated by acute
      respiratory failure, gastrointestinal bleeding and a surgical site infection of
      the thoracic incision; Escherichia coli and Klebsiella pneumonia were isolated.
      After surgical debridement drainage and prolonged antibiotic therapy, the wound
      healed correctly. His emergency chest computed tomography upon readmission for
      the acute onset of a beating tumefaction at the TA-TAVI site showed a false
      aneurysm of the LV apex. The apex was closed directly during emergency surgery.
      The postoperative course was uneventful. Surgical site infection after TA-TAVI,
      its frequency, treatment and potential role as an underlying cause of this severe
      complication are discussed. 

PMID- 24092467
TI  - An azygos vein aneurysm resected by video-assisted thoracic surgery after
      preoperative evaluation of multidetector computed tomography.
AB  - Azygos vein aneurysm is very rare and most cases are detected incidentally. We
      report a safe resection of azygos vein aneurysm by video-assisted thoracoscopic
      surgery (VATS) under preoperative evaluation of thrombus by multidetector
      computed tomography (MDCT). A 60-year old woman presented to our department due
      to a mediastinal mass revealed by enhanced CT. A dynamic enhanced-CT scan showed
      a dilated azygos vein with great enhancement in the early phase. Under the
      diagnosis of azygos vein aneurysm, we analysed the aneurysm by MDCT and confirmed
      that there was no thrombus within the aneurysm. The resection of the aneurysm by
      VATS was performed safely. She was discharged 4 days after surgery. 

PMID- 24092468
TI  - The IRF family transcription factors at the interface of innate and adaptive
      immune responses.
AB  - The interferon-regulatory factor (IRF) family, originally identified as
      transcriptional regulators of the type I interferon system, consists of nine
      members in mammals. A large number of studies have revealed the versatile and
      critical functions performed by this transcription factor family in immunity and
      other biological processes. Most notably, the advances in the study of signal
      transducing innate immune receptors have placed many IRF members as central
      mediators in the regulation of innate immune responses. In parallel, mechanistic
      studies have made it clearer that many IRFs exert their function either in
      cooperation or competition with other factors. In this article, we discuss
      current advances on the multipurpose and critical functions of IRFs in the
      regulation of innate immunity, particularly as they instruct adaptive immunity. 

PMID- 24092469
TI  - IL-1beta strikingly enhances antigen-driven CD4 and CD8 T-cell responses.
AB  - Protective immune response requires massive expansion of antigen-triggered naive
      cells, extensive differentiation into effector cells, migration of effectors into
      the periphery, and generation of a functional memory compartment. IL-1beta
      strikingly enhances expansion of antigen-primed CD8 and CD4 T cells in vivo. Its
      T-cell expansion in lymph nodes and spleen was direct, requiring that the
      stimulated T cells express IL-1R1. Immunization in the presence of IL-1beta
      increases the frequency of IL-17- and IFN-gamma-producing cells among primed CD4
      cells and the frequency of granzyme B-expressing and IFN-gamma-producing cells
      and of cytotoxic cells among primed CD8 cells. IL-1beta-induced increase in the
      number of the activated CD4 and CD8 cells and augmented differentiation of the
      antigen-triggered T cells is very pronounced in liver and lungs. CD4 and CD8
      cells primed in the presence of IL-1beta display augmented cell number and
      enhanced cytokine production when rechallenged 2 mo after priming with antigen
      and lipopolysaccharide (LPS). In five in vivo models, IL-1beta enhanced the
      protective value of weak vaccines. Preliminary analysis of in vivo gene
      expression in CD4 cells stimulated with IL-1beta revealed that IL-1beta caused
      gene expression changes consistent with the up-regulation of pathways involved in
      cell replication, cell survival, and enhanced energy metabolism. Thus, IL-1beta
      enhances antigen-primed CD4 and CD8 T-cell expansion, differentiation, and
      migration to the periphery and memory, the specific functions required for
      generation of effective protective immune responses. 

PMID- 24092470
TI  - Immunology taught by human genetics.
AB  - Human genetic studies are rarely conducted for immunological purposes. Instead,
      they are typically driven by medical and evolutionary goals, such as
      understanding the predisposition or resistance to infectious or inflammatory
      diseases, the pathogenesis of such diseases, and human evolution in the context
      of the long-standing relationships between humans and their commensal and
      environmental microbes. However, the dissection of these experiments of Nature
      has also led to major immunological advances. In this review, we draw on some of
      the immunological lessons learned in the three branches of human molecular
      genetics most relevant to immunology: clinical genetics, epidemiological
      genetics, and evolutionary genetics. We argue that human genetics has become a
      new frontier not only for timely studies of specific features of human immunity,
      but also for defining general principles of immunity. These studies teach us
      about immunity as it occurs under "natural" conditions, through the transition
      from the almost complete wilderness that existed worldwide until about a century
      ago to the current unevenly distributed medically shaped environment. Hygiene,
      vaccines, antibiotics, and surgery have considerably decreased the burden of
      infection, but these interventions have been available only recently, so have yet
      to have a major impact on patterns of genomic diversity, making it possible to
      carry out unbiased evolutionary studies at the population level. Clinical genetic
      studies of childhood phenotypes have not been blurred by modern medicine either.
      Instead, medical advances have actually facilitated such studies, by making it
      possible for children with life-threatening infections to survive. In addition,
      the prevention and treatment of infectious diseases have increased life
      expectancy at birth from ~20 yr to ~80 yr, providing unique opportunities to
      study the genetic basis of immunological phenomena against which there is no
      natural counterselection, such as reactivation and secondary infectious diseases
      and breakdown of self-tolerance manifesting as autoimmunity, in populations of
      adult and aging patients. Recently developed deep sequencing and stem cell
      technologies are of unprecedented power, and their application to human genetics
      is opening up exciting and timely possibilities for young immunologists seeking
      uncharted waters to explore. 

PMID- 24092471
TI  - The epigenetics of early lymphocyte development.
AB  - The mammalian genome is highly structured, both spatially and functionally.
      Chromosomes are organized into specific territories, which are further folded
      into euchromatic or heterochromatic compartments. The euchromatic compartment
      often contains domains decorated with activating epigenetic marks, whereas
      heterochromatic regions lack activating marks or bear repressive ones. During
      lymphocyte development, gene segments move between these compartments.
      Additionally, some genes undergoing changes in transcriptional activity also
      display elaborate alterations in chromatin folding. Lineage-specific
      transcription factors help mediate these reconfigurations. Herein, I describe how
      genetic loci encoding for key regulators switch nuclear neighborhoods and
      reorganize their 3D structures to drive cell fate. 

PMID- 24092472
TI  - Personalized prediction of EGFR mutation-induced drug resistance in lung cancer.
AB  - EGFR mutation-induced drug resistance has significantly impaired the potency of
      small molecule tyrosine kinase inhibitors in lung cancer treatment. Computational
      approaches can provide powerful and efficient techniques in the investigation of
      drug resistance. In our work, the EGFR mutation feature is characterized by the
      energy components of binding free energy (concerning the mutant-inhibitor
      complex), and we combine it with specific personal features for 168 clinical
      subjects to construct a personalized drug resistance prediction model. The 3D
      structure of an EGFR mutant is computationally predicted from its protein
      sequence, after which the dynamics of the bound mutant-inhibitor complex is
      simulated via AMBER and the binding free energy of the complex is calculated
      based on the dynamics. The utilization of extreme learning machines and leave-one
      out cross-validation promises a successful identification of resistant subjects
      with high accuracy. Overall, our study demonstrates advantages in the development
      of personalized medicine/therapy design and innovative drug discovery. 

PMID- 24092473
TI  - Patient safety problem identification and solution sharing among rural community
      pharmacists.
AB  - OBJECTIVES: To implement a communication network for safety problem
      identification and solution sharing among rural community pharmacists and to
      report participating pharmacists' perceived value and impact of the network on
      patient safety after 1 year of implementation. DESIGN: Action research study.
      SETTING: Rural community pharmacies in Nebraska from January 2010 to April 2011.
      PARTICIPANTS: Rural community pharmacists who voluntarily agreed to join the
      Pharmacists for Patient Safety Network in Nebraska. INTERVENTION: Pharmacists
      reported errors, near misses, and safety concerns through Web-based event
      reporting. A rapid feedback process was used to provide patient safety solutions
      to consider implementing across the network. MAIN OUTCOME MEASURES: Qualitative
      interviews were conducted 1 year after program implementation with participating
      pharmacists to assess use of the reporting system, value of the disseminated
      safety solutions, and perceived impact on patient safety in pharmacies. RESULTS:
      30 of 38 pharmacists participating in the project completed the interviews. The
      communication network improved pharmacist awareness, promoted open discussion and
      knowledge sharing, contributed to practice vigilance, and led to incorporation of
      proactive safety prevention practices. CONCLUSION: Despite low participation in
      error and near-miss reporting, a dynamic communication network designed to
      rapidly disseminate evidence-based patient safety strategies to reduce risk was
      valued and effective at improving patient safety practices in rural community
      pharmacies.

PMID- 24092474
TI  - Incidence and impact on prognosis of bleeding during percutaneous coronary
      interventions in patients with chronic kidney disease.
AB  - BACKGROUND: Limited information exists on the prognostic impact of bleeding after
      percutaneous coronary intervention (PCI) in patients with chronic kidney disease
      (CKD). We investigated the impact of bleeding after PCI on the outcome of these
      patients. METHODS: The study included 2,934 patients with estimated creatinine
      clearance <60 ml/min. Bleeding events within 30 days after PCI were assessed
      using the Bleeding Academic Research Consortium (BARC) criteria. The primary
      outcome was 1-year mortality. RESULTS: Bleeding events occurred in 485 patients
      (16.5 %). BARC classes were: class 1 (n = 155), class 2 (n = 73), class 3a (n =
      182), class 3b (n = 68), class 3c (n = 6) and class 4 (n = 1). There were 212
      deaths over the first year after PCI: 60 deaths in patients who bled and 152
      deaths in patients who did not bleed (Kaplan-Meier [KM] estimates, 12.5 and 6.3
      %; odds ratio [OR] = 2.11, 95 % confidence interval [CI] 1.57-2.83, P < 0.001).
      Nonfatal myocardial infarction occurred in 71 patients who bled and in 141
      patients who did not bleed (KM estimates, 14.8 and 5.8 %; OR = 2.70 [2.05-3.55],
      P < 0.001). After adjustment, bleeding was independently associated with
      increased risk of 1-year mortality (adjusted hazard ratio [HR] = 1.90 [1.33
      2.72], P < 0.001) and myocardial infarction (adjusted HR = 2.74 [1.99-3.78], P <
      0.001). Bleeding improved the discriminatory power of the multivariable model for
      prediction of mortality (absolute and relative integrated discrimination
      improvement [IDI], 0.011 and 15.4 %; P = 0.004) or myocardial infarction
      (absolute and relative IDI, 0.017 and 70.8 %; P < 0.001). CONCLUSIONS: Peri-PCI
      bleeding in patients with CKD is independently associated with the increased risk
      of 1-year mortality and nonfatal myocardial infarction.

PMID- 24092475
TI  - Accuracy of point-of-care multiorgan ultrasonography for the diagnosis of
      pulmonary embolism.
AB  - BACKGROUND: Presenting signs and symptoms of pulmonary embolism (PE) are
      nonspecific, favoring a large use of second-line diagnostic tests such as
      multidetector CT pulmonary angiography (MCTPA), thus exposing patients to high
      dose radiation and to potential serious complications. We investigated the
      diagnostic performance of multiorgan ultrasonography (lung, heart, and leg vein
      ultrasonography) and whether multiorgan ultrasonography combined to Wells score
      and D-dimer could safely reduce MCTPA tests. METHODS: Consecutive adult patients
      suspected of PE and with a Wells score > 4 or a positive D-dimer result were
      prospectively enrolled in three EDs. Final diagnosis was obtained with MCTPA.
      Multiorgan ultrasonography was performed before MCTPA and considered diagnostic
      for PE if one or more subpleural infarcts, right ventricular dilatation, or DVT
      was detected. If multiorgan ultrasonography was negative for PE, an alternative
      ultrasonography diagnosis was sought. Accuracies of each single-organ and
      multiorgan ultrasonography were calculated. RESULTS: PE was diagnosed in 110 of
      357 enrolled patients (30.8%). Multiorgan ultrasonography yielded a sensitivity
      of 90% and a specificity of 86.2%, lung ultrasonography 60.9% and 95.9%, heart
      ultrasonography 32.7% and 90.9%, and vein ultrasonography 52.7% and 97.6%,
      respectively. Among the 132 patients (37%) with multiorgan ultrasonography
      negative for PE plus an alternative ultrasonographic diagnosis or plus a negative
      D-dimer result, no patients received PE as a final diagnosis. CONCLUSIONS:
      Multiorgan ultrasonography is more sensitive than single-organ ultrasonography,
      increases the accuracy of clinical pretest probability estimation in patients
      with suspected PE, and may safely reduce the MCTPA burden. TRIAL REGISTRY:
      ClinicalTrials.gov; No.: NCT01635257; URL: www.clinicaltrials.gov.

PMID- 24092476
TI  - Pharmacologic intervention for managing uterine atony and related maternal
      hemorrhage: what is the most effective drug dose?

PMID- 24092477
TI  - Iliac artery rupture related to balloon insertion for placenta accreta causing
      maternal hemorrhage and neonatal compromise.
AB  - PURPOSE: The use of internal iliac artery balloons for prevention of hemorrhage
      in cases of placenta accreta is increasing. Most described complications of this
      technique are maternal and thromboembolic in nature. Complications related to
      vascular rupture are rare, their presentation is not well described, and the
      resultant neonatal consequences are infrequently reported. CLINICAL FEATURES: A
      35-yr-old term parturient with suspected placenta accreta underwent prophylactic
      endovascular placement of iliac balloons prior to Cesarean delivery. The patient
      complained of contraction-like pain during balloon placement, and an arterial
      wall tear was discovered after abdominal incision. This produced significant
      maternal bleeding and the birth of a neonate with an umbilical venous pH of 6.95
      and Apgar scores of 3 and 7. CONCLUSION: In addition to the known maternal risks,
      fetal risks must be considered when planning the placement of endovascular iliac
      balloons during pregnancy. We recommend continuous monitoring of maternal and
      fetal status when performing the procedure. Contraction-like pain during
      placement should raise the suspicion of arterial disruption.

PMID- 24092478
TI  - Acute hypoxemia in a parturient with primary ciliary dyskinesia following the
      administration of intravenous oxytocin: a case report.
AB  - PURPOSE: We present the case of a parturient diagnosed with primary ciliary
      dyskinesia with secondary bronchiectasis who developed significant hypoxemia
      following administration of intravenous oxytocin during Cesarean delivery under
      spinal anesthesia. This case suggests that oxytocin can affect pulmonary vascular
      tone and interfere with the protective effects of hypoxic vasoconstriction.
      CLINICAL FEATURES: A 35-yr-old primigravida at 37 weeks gestation presented for a
      scheduled Cesarean delivery due to breech positioning and fetal abnormalities.
      The patient had a diagnosis of primary ciliary dyskinesia and had undergone a
      right middle lobectomy seven years earlier for resultant bronchiectasis.
      Pulmonary function testing in the month prior to delivery showed a 4% decline in
      her baseline FEV1 to 1.06 L (32% of predicted value) but she was functionally
      well. The patient initially had an uneventful spinal anesthetic and maintained an
      oxygen saturation of 97% on room air in the supine position until delivery of her
      baby. An intravenous infusion of oxytocin for uterine contraction was started
      following removal of the placenta. The patient then became acutely hypoxemic with
      a drop in room air saturation to 84% but with no other accompanying hemodynamic
      instability. Maternal oxygen saturation did not improve with the addition of
      supplemental oxygen, and the patient had a significant arterial-alveolar oxygen
      gradient suggesting an intrapulmonary shunt. No supporting clinical, radiologic,
      or laboratory evidence of a thrombotic, air, or amniotic fluid embolism or mucous
      plug was detected. The patient remained hypoxemic during the postoperative period
      with gradual improvement back to baseline saturation in approximately 48 hr.
      CONCLUSION: The vasodilatory effects of intravenous oxytocin on the pulmonary
      vasculature may worsen shunting and interfere with hypoxic pulmonary
      vasoconstriction, producing clinically significant hypoxemia in patients with
      comorbid lung disease. Oxytocin should be used with caution in patients with
      compromised lung function.

PMID- 24092479
TI  - Monitoring of neuromuscular blockade in one muscle group alone may not reflect
      recovery of total muscle function in patients with ocular myasthenia gravis.
AB  - PURPOSE: We report on two patients with ocular myasthenia gravis who received
      rocuronium, followed later by sugammadex to reverse neuromuscular blockade.
      Recovery was monitored simultaneously at the adductor pollicis muscle (APM) and
      the corrugator supercilii muscle (CSM). CLINICAL FEATURES: Two patients with
      ocular myasthenia gravis (case 1: 74 yr-old female, 54 kg; case 2: 71 yr-old
      male, 72 kg) were scheduled for surgery under general anesthesia. Neuromuscular
      blockade was induced with rocuronium 0.3 mg.kg(-1) after placing two separate
      monitors at the APM and the CSM, respectively. Additional doses of rocuronium 0.1
      0.2 mg.kg(-1) were given to maintain neuromuscular blockade at fewer than two
      twitches at the APM during surgery. Train-of-four response at the CSM did not
      show recovery of the twitch after its initial disappearance. At the end of
      surgery, sugammadex was administered. Twitch height at the APM recovered to the
      control value in 12 min (case 1) and 13 min (case 2) after sugammadex
      administration; however, twitch height at the CSM took 26 min (case 1) and 14 min
      (case 2) to recover to the control value. CONCLUSION: After rocuronium-induced
      paralysis in both patients with ocular myasthenia, spontaneous recovery and
      sugammadex-assisted recovery were slower at the CSM than at the APM. In patients
      without the disorder, CSM recovery is faster than APM recovery. Thus, in ocular
      myasthenia gravis, neuromuscular recovery at the APM may not reflect recovery of
      all muscles.

PMID- 24092480
TI  - Observed-score equating: an overview.
AB  - In this paper, an overview of the observed-score equating (OSE) process is
      provided from the perspective of a unifying equating framework (von Davier in von
      Davier (Ed.), Statistical models for test equating, scaling, and linking,
      Springer, New York, pp. 1-17, 2011b). The framework includes all OSE approaches.
      Issues related to the test, common items, and sampling designs and their
      relationship to measurement and equating are discussed. Challenges to the
      equating process, model assumptions, and approaches to equating evaluation are
      also presented. The equating process is illustrated step-by-step with a real data
      example from a licensure test.

PMID- 24092481
TI  - A Bayesian modeling approach for generalized semiparametric structural equation
      models.
AB  - In behavioral, biomedical, and psychological studies, structural equation models
      (SEMs) have been widely used for assessing relationships between latent
      variables. Regression-type structural models based on parametric functions are
      often used for such purposes. In many applications, however, parametric SEMs are
      not adequate to capture subtle patterns in the functions over the entire range of
      the predictor variable. A different but equally important limitation of
      traditional parametric SEMs is that they are not designed to handle mixed data
      types-continuous, count, ordered, and unordered categorical. This paper develops
      a generalized semiparametric SEM that is able to handle mixed data types and to
      simultaneously model different functional relationships among latent variables. A
      structural equation of the proposed SEM is formulated using a series of
      unspecified smooth functions. The Bayesian P-splines approach and Markov chain
      Monte Carlo methods are developed to estimate the smooth functions and the
      unknown parameters. Moreover, we examine the relative benefits of semiparametric
      modeling over parametric modeling using a Bayesian model-comparison statistic,
      called the complete deviance information criterion (DIC). The performance of the
      developed methodology is evaluated using a simulation study. To illustrate the
      method, we used a data set derived from the National Longitudinal Survey of
      Youth.

PMID- 24092482
TI  - Modeling differences in the dimensionality of multiblock data by means of
      clusterwise simultaneous component analysis.
AB  - Given multivariate multiblock data (e.g., subjects nested in groups are measured
      on multiple variables), one may be interested in the nature and number of
      dimensions that underlie the variables, and in differences in dimensional
      structure across data blocks. To this end, clusterwise simultaneous component
      analysis (SCA) was proposed which simultaneously clusters blocks with a similar
      structure and performs an SCA per cluster. However, the number of components was
      restricted to be the same across clusters, which is often unrealistic. In this
      paper, this restriction is removed. The resulting challenges with respect to
      model estimation and selection are resolved. 

PMID- 24092483
TI  - Constrained Candecomp/Parafac via the Lasso.
AB  - The Candecomp/Parafac (CP) model is a well-known tool for summarizing a three-way
      array by extracting a limited number of components. Unfortunately, in some cases,
      the model suffers from the so-called degeneracy, that is a solution with
      diverging and uninterpretable components. To avoid degeneracy, orthogonality
      constraints are usually applied to one of the component matrices. This solves the
      problem only from a technical point of view because the existence of orthogonal
      components underlying the data is not guaranteed. For this purpose, we consider
      some variants of the CP model where the orthogonality constraints are relaxed
      either by constraining only a pair, or a subset, of components or by stimulating
      the CP solution to be possibly orthogonal. We theoretically clarify that only the
      latter approach, based on the least absolute shrinkage and selection operator and
      named the CP-Lasso, is helpful in solving the degeneracy problem. The results of
      the application of CP-Lasso on simulated and real life data show its
      effectiveness. 

PMID- 24092484
TI  - A nondegenerate penalized likelihood estimator for variance parameters in
      multilevel models.
AB  - Group-level variance estimates of zero often arise when fitting multilevel or
      hierarchical linear models, especially when the number of groups is small. For
      situations where zero variances are implausible a priori, we propose a maximum
      penalized likelihood approach to avoid such boundary estimates. This approach is
      equivalent to estimating variance parameters by their posterior mode, given a
      weakly informative prior distribution. By choosing the penalty from the log-gamma
      family with shape parameter greater than 1, we ensure that the estimated variance
      will be positive. We suggest a default log-gamma(2,lambda) penalty with lambda ->
      0, which ensures that the maximum penalized likelihood estimate is approximately
      one standard error from zero when the maximum likelihood estimate is zero, thus
      remaining consistent with the data while being nondegenerate. We also show that
      the maximum penalized likelihood estimator with this default penalty is a good
      approximation to the posterior median obtained under a noninformative prior.Our
      default method provides better estimates of model parameters and standard errors
      than the maximum likelihood or the restricted maximum likelihood estimators. The
      log-gamma family can also be used to convey substantive prior information. In
      either case-pure penalization or prior information-our recommended procedure
      gives nondegenerate estimates and in the limit coincides with maximum likelihood
      as the number of groups increases.

PMID- 24092485
TI  - Assessing parameter invariance in the BLIM: bipartition models.
AB  - In knowledge space theory, the knowledge state of a student is the set of all
      problems he is capable of solving in a specific knowledge domain and a knowledge
      structure is the collection of knowledge states. The basic local independence
      model (BLIM) is a probabilistic model for knowledge structures. The BLIM assumes
      a probability distribution on the knowledge states and a lucky guess and a
      careless error probability for each problem. A key assumption of the BLIM is that
      the lucky guess and careless error probabilities do not depend on knowledge
      states (invariance assumption). This article proposes a method for testing the
      violations of this specific assumption. The proposed method was assessed in a
      simulation study and in an empirical application. The results show that (1) the
      invariance assumption might be violated by the empirical data even when the
      model's fit is very good, and (2) the proposed method may prove to be a promising
      tool to detect invariance violations of the BLIM. 

PMID- 24092486
TI  - The special sign indeterminacy of the direct-fitting Parafac2 model: some
      implications, cautions, and recommendations for simultaneous component analysis.
AB  - Parafac2 is the most flexible Simultaneous Component Analysis (SCA) model that
      produces an essentially unique solution. In this paper, we discuss how Parafac2's
      special sign indeterminacy affects applications of SCA, and we reveal how an
      external criterion variable can be used to ensure that estimated Parafac2 weights
      are meaningfully signed across the levels of the nesting mode. We present an
      example with real data from clinical psychology that illustrates the importance
      of Parafac2's special sign indeterminacy, as well as the effectiveness of our
      proposed solution. We also discuss the implications of our results for general
      applications of SCA. 

PMID- 24092487
TI  - Nonlinear regime-switching state-space (RSSS) models.
AB  - Nonlinear dynamic factor analysis models extend standard linear dynamic factor
      analysis models by allowing time series processes to be nonlinear at the latent
      level (e.g., involving interaction between two latent processes). In practice, it
      is often of interest to identify the phases--namely, latent "regimes" or classes-
      during which a system is characterized by distinctly different dynamics. We
      propose a new class of models, termed nonlinear regime-switching state-space
      (RSSS) models, which subsumes regime-switching nonlinear dynamic factor analysis
      models as a special case. In nonlinear RSSS models, the change processes within
      regimes, represented using a state-space model, are allowed to be nonlinear. An
      estimation procedure obtained by combining the extended Kalman filter and the Kim
      filter is proposed as a way to estimate nonlinear RSSS models. We illustrate the
      utility of nonlinear RSSS models by fitting a nonlinear dynamic factor analysis
      model with regime-specific cross-regression parameters to a set of experience
      sampling affect data. The parallels between nonlinear RSSS models and other well
      known discrete change models in the literature are discussed briefly.

PMID- 24092488
TI  - An application of the LC-LSTM framework to the self-esteem instability case.
AB  - The present research evaluates the stability of self-esteem as assessed by a
      daily version of the Rosenberg (Society and the adolescent self-image, Princeton
      University Press, Princeton, 1965) general self-esteem scale (RGSE). The scale
      was administered to 391 undergraduates for five consecutive days. The
      longitudinal data were analyzed using the integrated LC-LSTM framework that
      allowed us to evaluate: (1) the measurement invariance of the RGSE, (2) its
      stability and change across the 5-day assessment period, (3) the amount of
      variance attributable to stable and transitory latent factors, and (4) the
      criterion-related validity of these factors. Results provided evidence for
      measurement invariance, mean-level stability, and rank-order stability of daily
      self-esteem. Latent state-trait analyses revealed that variances in scores of the
      RGSE can be decomposed into six components: stable self-esteem (40 %), ephemeral
      (or temporal-state) variance (36 %), stable negative method variance (9 %),
      stable positive method variance (4 %), specific variance (1 %) and random error
      variance (10 %). Moreover, latent factors associated with daily self-esteem were
      associated with measures of depression, implicit self-esteem, and grade point
      average.

PMID- 24092489
TI  - Modelling dyadic interaction with Hawkes processes.
AB  - We apply the Hawkes process to the analysis of dyadic interaction. The Hawkes
      process is applicable to excitatory interactions, wherein the actions of each
      individual increase the probability of further actions in the near future. We
      consider the representation of the Hawkes process both as a conditional intensity
      function and as a cluster Poisson process. The former treats the probability of
      an action in continuous time via non-stationary distributions with arbitrarily
      long historical dependency, while the latter is conducive to maximum likelihood
      estimation using the EM algorithm. We first outline the interpretation of the
      Hawkes process in the dyadic context, and then illustrate its application with an
      example concerning email transactions in the work place. 

PMID- 24092490
TI  - Harmonic regression and scale stability.
AB  - Monitoring a very frequently administered educational test with a relatively
      short history of stable operation imposes a number of challenges. Test scores
      usually vary by season, and the frequency of administration of such educational
      tests is also seasonal. Although it is important to react to unreasonable changes
      in the distributions of test scores in a timely fashion, it is not a simple
      matter to ascertain what sort of distribution is really unusual. Many commonly
      used approaches for seasonal adjustment are designed for time series with evenly
      spaced observations that span many years and, therefore, are inappropriate for
      data from such educational tests. Harmonic regression, a seasonal-adjustment
      method, can be useful in monitoring scale stability when the number of years
      available is limited and when the observations are unevenly spaced. Additional
      forms of adjustments can be included to account for variability in test scores
      due to different sources of population variations. To illustrate, real data are
      considered from an international language assessment. 

PMID- 24092491
TI  - Explanatory multidimensional multilevel random item response model: an
      application to simultaneous investigation of word and person contributions to
      multidimensional lexical representations.
AB  - This paper presents an explanatory multidimensional multilevel random item
      response model and its application to reading data with multilevel item
      structure. The model includes multilevel random item parameters that allow
      consideration of variability in item parameters at both item and item group
      levels. Item-level random item parameters were included to model unexplained
      variance remaining when item related covariates were used to explain variation in
      item difficulties. Item group-level random item parameters were included to model
      dependency in item responses among items having the same item stem. Using the
      model, this study examined the dimensionality of a person's word knowledge,
      termed lexical representation, and how aspects of morphological knowledge
      contributed to lexical representations for different persons, items, and item
      groups. 

PMID- 24092492
TI  - Cross-sectional and longitudinal studies suggest pharmacological treatment used
      in patients with glucokinase mutations does not alter glycaemia.
AB  - AIMS/HYPOTHESIS: Heterozygous glucokinase (GCK) mutations cause mild, fasting
      hyperglycaemia from birth. Although patients are usually asymptomatic and have
      glycaemia within target ranges, some are put on pharmacological treatment. We
      aimed to investigate how many patients are on pharmacological treatment and the
      impact of treatment on glycaemic control. METHODS: Treatment details were
      ascertained for 799 patients with heterozygous GCK mutations. In a separate,
      longitudinal study, HbA1c was obtained for 16 consecutive patients receiving
      insulin (n = 10) or oral hypoglycaemic agents (OHAs) (n = 6) whilst on treatment,
      and again having discontinued treatment following a genetic diagnosis of GCK
      MODY. For comparison, HbA1c before and after genetic testing was studied in a
      control group (n = 18) not receiving pharmacological therapy. RESULTS: At
      referral for genetic testing, 168/799 (21%) of patients were on pharmacological
      treatment (13.5% OHAs, 7.5% insulin). There was no difference in the HbA1c of
      these patients compared with those receiving no treatment(median [IQR]: 48 [43,
      51] vs 46 [43, 50] mmol/mol, respectively; 6.5% [6.1%, 6.8%] vs 6.4% [6.1%,
      6.7%]; p = 0.11). Following discontinuation of pharmacological treatment in 16
      patients, HbA1c did not change. The mean change in HbA1c was -0.68 mmol/mol (95%
      CI: -2.97, 1.61) (-0.06% [95% CI: -0.27, 0.15]). CONCLUSIONS/INTERPRETATION:
      Prior to a genetic diagnosis, 21% of patients were on pharmacological treatment.
      HbA1c was no higher than in untreated patients and did not change when therapy
      was discontinued, suggesting no impact on glycaemia. The lack of response to
      pharmacological therapy is likely to reflect the regulated hyperglycaemia seen in
      these patients owing to their glucose sensing defect and is an example of
      pharmacogenetics.

PMID- 24092493
TI  - Age-related differences in glycaemic control in diabetes.

PMID- 24092495
TI  - In situ fluorescence spectroscopy correlates ionomer degradation to reactive
      oxygen species generation in an operating fuel cell.
AB  - The rate of generation of reactive oxygen species (ROS) within the polymer
      electrolyte membrane (PEM) of an operating proton exchange member fuel cell
      (PEMFC) was monitored using in situ fluorescence spectroscopy. A modified barrier
      layer was introduced between the PEM and the electrocatalyst layer to eliminate
      metal-dye interactions and fluorescence resonance energy transfer (FRET) effects
      during measurements. Standard fuel cell operating parameters (temperature,
      relative humidity, and electrode potential) were systematically varied to
      evaluate their influence on the rate of ROS generation during PEMFC operation.
      Independently, the macroscopic rate of PEM degradation was measured by monitoring
      the fluoride ion emission rate (FER) in the effluent stream at each operating
      condition. The ROS generation reaction rate constant (estimated from the in situ
      fluorescence experiments) correlated perfectly with the measured FER across all
      conditions, demonstrating unequivocally for the first time that a direct
      correlation exists between in situ ROS generation and PEM macroscopic
      degradation. The activation energy for ROS generation within the PEM was
      estimated to be 12.5 kJ mol(-1). 

PMID- 24092494
TI  - Youth-caregiver agreement on clinical high-risk symptoms of psychosis.
AB  - Early identification of individuals who will go on to develop schizophrenia is a
      difficult endeavor. The variety of symptoms experienced by clinical high-risk
      youth make it difficult to identify who will eventually develop schizophrenia in
      the future. Efforts are being made, therefore, to more accurately identify at
      risk individuals and factors that predict conversion to psychosis. As in most
      assessments of children and adolescents, however, both youth and parental report
      of symptomatology and resulting dysfunction are important to assess. The goals of
      the current study were to assess the extent of cross-informant agreement on the
      Structured Interview for Prodromal Symptoms (SIPS), a widely-used tool employed
      to determine clinical high-risk status. A total of 84 youth-caregiver pairs
      participated. Youth and caregiver raters displayed moderate overall agreement on
      SIPS-rated symptoms. Both youth and caregiver ratings of youth symptomatology
      contributed significantly to predicting conversion to psychosis. In addition,
      youth age and quality of youth-caregiver relationships appear to be related to
      cross-informant symptom ratings. Despite differences on individual SIPS domains,
      the majority of dyads agreed on youth clinical high-risk status. Results
      highlight the potential clinical utility of using caregiver informants to
      determine youth psychosis risk. 

PMID- 24092496
TI  - Novel evidence in support of the bilingual advantage: influences of task demands
      and experience on cognitive control and working memory.
AB  - The bilingual advantage-enhanced cognitive control relative to monolinguals
      possibly occurs due to experience engaging general cognitive mechanisms in order
      to manage two languages. Supporting this hypothesis is evidence that bimodal
      (signed language-spoken language) bilinguals do not demonstrate such an
      advantage, presumably because the distinct language modalities reduce conflict
      and control demands. We hypothesized that the mechanism responsible for the
      bilingual advantage is the interplay between (a) the magnitude of bilingual
      management demands and (b) the amount of experience managing those demands. We
      recruited adult bimodal bilinguals with high bilingual management demands and
      examined cognitive control and working memory capacity longitudinally. After
      gaining experience managing high bilingual management demands, participants
      outperformed themselves from 2 years earlier on cognitive abilities associated
      with managing the bilingual demands. These results suggest that cognitive control
      outcomes for bilinguals vary as a function of the mechanisms recruited during
      bilingual management and the amount of experience managing the bilingual demands.

PMID- 24092497
TI  - Establishing a reference group for distal 18q-: clinical description and
      molecular basis.
AB  - Although constitutional chromosome abnormalities have been recognized since the
      1960s, clinical characterization and development of treatment options have been
      hampered by their obvious genetic complexity and relative rarity. Additionally,
      deletions of 18q are particularly heterogeneous, with no two people having the
      same breakpoints. We identified 16 individuals with deletions that, despite
      unique breakpoints, encompass the same set of genes within a 17.6-Mb region. This
      group represents the most genotypically similar group yet identified with distal
      18q deletions. As the deletion is of average size when compared with other 18q
      deletions, this group can serve as a reference point for the clinical and
      molecular description of this condition. We performed a thorough medical record
      review as well as a series of clinical evaluations on 14 of the 16 individuals.
      Common functional findings included developmental delays, hypotonia, growth
      hormone deficiency, and hearing loss. Structural anomalies included foot
      anomalies, ear canal atresia/stenosis, and hypospadias. The majority of
      individuals performed within the low normal range of cognitive ability but had
      more serious deficits in adaptive abilities. Of interest, the hemizygous region
      contains 38 known genes, 26 of which are sufficiently understood to tentatively
      determine dosage sensitivity. Published data suggest that 20 are unlikely to
      cause an abnormal phenotype in the hemizygous state and five are likely to be
      dosage sensitive: TNX3, NETO1, ZNF407, TSHZ1, and NFATC. A sixth gene, ATP9B, may
      be conditionally dosage sensitive. Not all distal 18q- phenotypes can be
      attributed to these six genes; however, this is an important advance in the
      molecular characterization of 18q deletions. 

PMID- 24092499
TI  - Marijuana use in America: whither are we bound?

PMID- 24092498
TI  - Plant antimicrobial peptides.
AB  - Plant antimicrobial peptides (AMPs) are a component of barrier defense system of
      plants. They have been isolated from roots, seeds, flowers, stems, and leaves of
      a wide variety of species and have activities towards phytopathogens, as well as
      against bacteria pathogenic to humans. Thus, plant AMPs are considered as
      promising antibiotic compounds with important biotechnological applications.
      Plant AMPs are grouped into several families and share general features such as
      positive charge, the presence of disulfide bonds (which stabilize the structure),
      and the mechanism of action targeting outer membrane structures. 

PMID- 24092502
TI  - Minimally invasive oesophagectomy more expensive than open despite shorter length
      of stay.
AB  - OBJECTIVES: The minimally invasive oesophagectomy (MIO) approach offers a number
      of advantages over open approaches including reduced discomfort, shorter length
      of stay and a faster recovery to baseline status. On the other hand, minimally
      invasive procedures typically are longer and consume greater disposable
      instrumentation, potentially resulting in a greater overall cost. The objective
      of this study was to compare costs associated with various oesophagectomy
      approaches for oesophageal cancer. METHODS: An institutional Resource Information
      Management System (RIMS) was queried for cost data relating to hospital
      expenditures (as opposed to billings or collections). The RIMS was searched for
      patients undergoing oesophagectomy for oesophageal cancer between 2003 and 2012
      via minimally invasive, open transthoracic (OTT) (including Ivor Lewis, modified
      McKeown or thoracoabdominal) or transhiatal approaches. Patients that were
      converted from minimally invasive to open, or involved hybrid procedures, were
      excluded. RESULTS: A total of 160 oesophagectomies were identified, including 61
      minimally invasive, 35 open transthoracic and 64 transhiatal. Costs on the day of
      surgery averaged higher in the MIO group ($12 476 +/- 2190) compared with the
      open groups, OTT ($8202 +/- 2512, P < 0.0001) or OTH ($5809 +/- 2575, P <
      0.0001). The median costs associated with the entire hospitalization also appear
      to be higher in the MIO group ($25 935) compared with OTT ($24 440) and OTH ($15
      248). The average length of stay was lowest in the MIO group (11 +/- 9 days)
      compared with OTT (19 +/- 18 days, P = 0.006) and OTH (18 +/- 28 days P = 0.07).
      The operative mortality was similar in the three groups (MIO = 3%, OTT = 9% and
      OTH = 3%). CONCLUSIONS: The operating theatre costs associated with minimally
      invasive oesophagectomy are significantly higher than OTT or OTH approaches.
      Unfortunately, a shorter hospital stay after MIO does not consistently offset
      higher surgical expense, as total hospital costs trend higher in the MIO
      patients. In an increasingly strained health care economy, efforts to reduce
      costs associated with the minimally invasive approach should address the
      inpatient hospitalization as well as operating theatre expenses.

PMID- 24092501
TI  - Functional relevance of D,L-sulforaphane-mediated induction of vimentin and
      plasminogen activator inhibitor-1 in human prostate cancer cells.
AB  - PURPOSE: D,L-Sulforaphane (SFN) is a promising chemopreventive agent with in vivo
      efficacy against prostate cancer in experimental rodents. This study was
      undertaken to determine the role of vimentin and plasminogen activator inhibitor
      1 (PAI-1) in anticancer effects of SFN. METHODS: Effect of SFN on levels of
      different proteins was determined by Western blotting or immunofluorescence
      microscopy. RNA interference of vimentin and PAI-1 was achieved by transient
      transfection. Apoptosis was quantified by flow cytometry. Transwell chambers were
      used to determine cell migration. RESULTS: Exposure of PC-3 and DU145 human
      prostate cancer cells to SFN resulted in induction of vimentin protein, which was
      accompanied by down-regulation of E-cadherin protein expression. The SFN-mediated
      induction of vimentin was also observed in a normal human prostate epithelial
      cell line. RNA interference of vimentin did not have any appreciable effect on
      early or late apoptosis resulting from SFN exposure. On the other hand, SFN
      mediated inhibition of PC-3 and DU145 cell migration was significantly augmented
      by knockdown of the vimentin protein. Knockdown of vimentin itself was inhibitory
      against cell migration. The SFN-treated cells also exhibited induction of PAI-1,
      which is an endogenous inhibitor of urokinase-type plasminogen activator system.
      Similar to vimentin, PAI-1 knockdown resulted in a modest augmentation of PC-3
      cell migration inhibition by SFN. Tumors from SFN-treated transgenic
      adenocarcinoma of mouse prostate mice showed a 1.7-fold increase in vimentin
      protein level compared with control tumors. CONCLUSION: The present study
      indicates that vimentin and PAI-1 inductions confer modest protection against SFN
      mediated inhibition of prostate cancer cell migration.

PMID- 24092504
TI  - Experimental model to evaluate the effect of hydrothorax and lobar resection on
      lung compliance.
AB  - OBJECTIVES: The objective of this study was to evaluate to what extent lung
      compliance is affected by the individual and combined action of lung resection
      and hydrothorax in an animal model. METHODS: Anaesthetized and mechanically
      ventilated rabbits (weight range 2 / 2.2 kg) were randomized in two groups: (i)
      experimental hydrothorax (from 2 to 8 ml) (n = 5) and (ii) right lower lobe
      lobectomy (n = 4) and right middle plus lower lobe resection (n = 2). To obtain
      lung compliance, we measured alveolar, oesophageal pressures and lung volume
      during slow inflation manoeuvres in control conditions and after hydrothorax or
      lung resection. Lung compliance was estimated as the change in lung volume
      divided by the change in transpulmonary pressure. Based on the changes in
      compliance of the whole lung, we calculated the corresponding changes in
      compliance of the right lung, which was directly exposed to unilateral
      hydrothorax and lobectomy. RESULTS: Average total lung compliance in the control
      was 3.3 +/- 0.8 (SD) ml/cmH2O. Eight millilitres of hydrothorax significantly
      decreased (P < 0.001) lung compliance to 2.7 +/- 0.7 ml/cmH2O and increased
      pleural liquid pressure at the bottom of the cavity from -1 cmH2O up to ~ 2.5-3
      cmH2O. Resection of the right lower lobe significantly decreased (P < 0.001) lung
      compliance to 1.75 +/- 0.3 ml/cmH2O. Resection of the right middle plus lower
      lobes significantly decreased (P < 0.001) lung compliance to 1.52 +/- 0.4
      ml/cmH2O. CONCLUSIONS: Following hydrothorax, the decrease in right lung
      compliance (~ 45%) was much greater than that expected based on the estimated
      decrease in right lung volume (20%). We attribute this difference to the fact
      that hydrothorax causes the lung to be exposed to positive, rather than sub
      atmospheric, pressure, causing atelectasis. Following lobectomy, right lung
      compliance decreased by 62 and 80% for estimated decreases in lung volume of 30
      and 60%. This difference could reflect inaccuracy in the estimate of lung volume
      reduction based on resected weight and/or surgical damage. We conclude that
      potential detrimental effects of hydrothorax and lobar resection decrease lung
      compliance and expose the lung to the risk of over-distension when a chest drain
      is applied.

PMID- 24092503
TI  - Morbidity and mortality in a large series of surgical patients with pulmonary
      metastases of colorectal carcinoma: a prospective multicentre Spanish study
      (GECMP-CCR-SEPAR).
AB  - OBJECTIVE: Little information is available on postoperative morbidity and
      mortality after pulmonary metastasectomy. We describe the postoperative morbidity
      and mortality in a large multicentre series of patients after a first surgical
      procedure for pulmonary metastases of colorectal carcinoma (CRC) and identify the
      pre- and intraoperative variables influencing the clinical outcome. METHODS: A
      prospective, observational and multicentre study was conducted. Data were
      collected from March 2008 to February 2010. Patients were grouped into Groups A
      and B according to the presence or absence of postoperative complications.
      Variables in both groups were compared by univariate and multivariate analyses. P
      values of <0.05 were considered statistically significant. RESULTS: A total of
      532 patients (64.5% males) from 32 hospitals were included. The mean (SD) ages of
      both study groups were similar [68 (10) vs 67 (10) years, P = NS). A total of
      1050 lung resections were performed (90% segmentectomies or wedge, n = 946 and
      10% lobectomies or greater, n = 104). Group A included 83 (15.6%) patients who
      developed a total of 100 complications. These included persistent air leaks in
      18, atelectasis in 13, pneumonia in 13, paralytic ileum in 12, arrhythmia in 9,
      acute respiratory distress syndrome in 4 and miscellanea in 31. Reoperation was
      performed in 5 (0.9%) patients due to persistent air leaks in 4 and lung
      ischaemia in 1. The mortality rate was 0.4% (n = 2). Causes of death were sepsis
      in 1 patient and ventricular fibrillation in 1. In the multivariate analysis,
      lobectomy or greater lung resection [odds ration (OR) 1.9, 95% confidence
      interval (95% CI) 1.04-3.3, P = 0.03], respiratory co-morbidity (OR 2.3, 95% CI
      1.1-4.6, P = 0.01) and cardiovascular co-morbidity (OR 2, 95% CI 1-3.8, P = 0.02)
      were independent risk factors for postoperative morbidity. Video-assisted surgery
      vs thoracotomy showed a protective effect (OR 0.3, 95% CI 0.1-0.8, P = 0.01).
      CONCLUSIONS: The first episode of lung surgery for pulmonary metastases of CRC
      was associated with very low mortality and reoperation rates (<1%). The
      postoperative morbidity rate was 16%. Independent risk factors of postoperative
      morbidity were major lung resection and respiratory and/or cardiovascular co
      morbidity. Video-assisted surgery showed a protective effect.

PMID- 24092505
TI  - Successful management of aorto-oesophageal fistula with dual oesophageal and
      aortic intervention.

PMID- 24092506
TI  - Prognostic factors in neuroendocrine tumours of the lung: a single-centre
      experience.
AB  - OBJECTIVES: To assess the independent prognostic role of histological subtypes,
      tumour size and lymph nodal involvement upon survival in lung neuroendocrine
      tumours (NETs). METHODS: A retrospective search of the database of the Department
      of Thoracic Surgery (Turin, Italy) identified 157 patients operated on for a
      newly diagnosed NET between January 1995 and December 2011. Multivariable Cox
      models were used to analyse predictors of overall survival and progression-free
      survival. RESULTS: According to histology, 71 (45.2%) were typical carcinoids
      (TCs), 35 (22.3%) atypical carcinoids (ACs), 37 (23.6%) large-cell neuroendocrine
      carcinomas (LCNCs) and 14 (8.9%) small-cell lung carcinomas (SCLCs). After a
      median follow-up time of 6.5 years, 60 patients died and 73 had a recurrence or
      died. The overall 5-, 10- and 15-year survival rates were 64%, 53% and 46%,
      respectively. Older age, histology (ACs, LCNCs and SCLCs vs TCs) and lymph nodal
      involvement were confirmed to be independent negative prognostic factors in the
      multivariable models for overall survival and progression-free survival.
      CONCLUSIONS: Tumour histology and lymph nodal involvement are definitively the
      predominant and relevant factors influencing survival. ACs showed an intermediate
      prognosis between TCs and poorly differentiated NETs.

PMID- 24092507
TI  - The consensus statement of the Paediatric Section of the Polish Society of
      Anaesthesiology and Intensive Therapy on general anaesthesia in children under 3
      years of age.

PMID- 24092508
TI  - Objective assessment of pain-related stress in mechanically ventilated newborns
      based on skin conductance fluctuations.
AB  - BACKGROUND: In the process of intensive care, neonates are exposed to stress and
      pain related to the repeated therapeutic- diagnostic procedures. The aim of this
      study was the objective assessment of stress intensity pain while performing
      selected procedures in neonates in the intensive care unit. METHODS: 32 neonates,
      with a mean body mass of 2,495 g, intubated and mechanically ventilated, and who
      underwent sedation and analgesia were qualified to the study. A stress reaction
      to suctioning from endotracheal tube and capillary blood taking for blood gas
      analysis was evaluated. For the pain stress evaluation, the conductance
      fluctuation method was used. RESULTS: 0.20 oscillations per second during the
      mechanical ventilation were obtained; during the suctioning, the number of
      oscillations increased to 0.33. With finger tip puncture, the number of
      oscillations was 0.35. The mean values obtained in the cases of suctioning and
      puncture differed significantly from the ones obtained at mechanical ventilation
      (P < 0.001) and did not differ between one another (P = 0.558). The oscillation
      proportion >= 0.33 s-1 was the lowest during the ventilation and it was
      significantly different (P < 0.001) from the values obtained at suctioning and
      finger tip puncture. There were no significant differences between these values.
      CONCLUSION: The measurement of conductivity of the skin as an objective tool to
      measure pain and discomfort during invasive procedures in neonatal intensive care
      shows that, despite the use of sedation and analgesia, neonates experience
      discomfort associated with the selected performance of therapeutic and diagnostic
      procedures.

PMID- 24092509
TI  - New generation pulse oximetry in the assessment of peripheral perfusion during
      general anaesthesia - a comparison between propofol and desflurane.
AB  - BACKGROUND: A pulse oximeter is a standard device for perioperative monitoring.
      It is well known that the early detection of tissue hypoxia is of great
      importance. It has been made easier due to a new generation pulse oximetry device
      from Masimo. This enables measurements of the peripheral perfusion index (PI) in
      real time. It has been found that volatile anaesthetics such as sevoflurane and
      desflurane increase the perfusion index. As we know, no data is available about
      perfusion index during propofol/remifentanil total intravenous anaesthesia.
      METHODS: ASA I and II class women scheduled for elective gynaecological surgery
      were eligible for the study. Patients were divided into two groups: group P
      receiving propofol/remifentanil intravenous anaesthesia and group D receiving
      desflurane/fentanyl general anaesthesia. PI was noted before anaesthesia, after
      remifentanil/fentanyl injection, after endotracheal intubation, at the beginning
      of surgery, during the procedure at ten minute intervals, at the end of the
      procedure, after awakening, after extubation and before discharge to the ward.
      RESULTS: Eighty-three patients were enrolled to the study. In both groups, PI
      increased significantly from the start to the end of surgery. There was a
      significant correlation between PI and end-tidal desflurane concentration (r =
      0.807; P = 0.001). No correlation was found between propofol or remifentanil
      concentrations and PI. CONCLUSION: Both intravenous propofol/remifentanil and
      desflurane/fentanyl general anaesthesia increase peripheral perfusion. An
      increase in end-tidal desflurane concentration raises peripheral perfusion.

PMID- 24092510
TI  - Anaesthetic management for endovascular treatment of unruptured intracranial
      aneurysms.
AB  - BACKGROUND: Endovascular techniques for treatment of intracranial aneurysms are
      increasingly commonly applied. In general, the procedures are short, require
      general anaesthesia and complete immobilisation of patients. The aim of the
      present study was to assess the usefulness of general anaesthesia with propofol
      and laryngeal mask airway for endovascular management of intracranial aneurysms
      based on analysis of haemodynamic stability. METHODS: The study encompassed 26
      patients undergoing endovascular treatment of intracranial aneurysms. The mean
      arterial pressure (MAP), heart rate (HR), bispectral index (BIS), end-tidal
      CO2(E(T)CO2) and haemoglobin saturation with oxygen (SpO2 ) were determined at
      eight measurement points: T1 - before anaesthesia induction, T2 - after
      induction, T3 - after LMA insertion, T4 - during arteriography, T5 - during
      "coiling" , T6 - at completion of propofol infusion, T7 - before LMA removal, T8 
      after LMA removal. RESULTS: MAP and HR were found significantly reduced between
      T2 and T1 . To maintain BIS within the range of 40-60, the following propofol
      infusion rates (in mg kg b.w.-1 h-1 ) were required: T2 - 4.5 +/- 0.3; T3 - 4.6
      +/- 0.7; T4 - 4.5 +/- 0.8 and T5 - 4.4 +/- 0.6. E T CO2 and SpO2 were not
      demonstrated to be changed. The mean duration of anaesthesia and of recovery was
      64.3 +/- 21.8 and 8.9 +/- 4.8 min, respectively. CONCLUSIONS: General anaesthesia
      with propofol and LMA ensures suitable conditions for endovascular treatment of
      intracranial aneurysms.

PMID- 24092511
TI  - Labour epidural analgesia in Poland in 2009 - a survey.
AB  - BACKGROUND: Labour analgesia in most developed countries is funded by the state,
      available to every woman in labour, and plays an important role in the everyday
      activities of most anaesthetists. This paper presents the second part of an
      Obstetric Anaesthesia Survey which was conducted in 2009. The first part of the
      Survey, relating to anaesthesia for caesarean sections, was published in 2010.
      METHODS: The author sent out 432 questionnaires containing questions about
      hospital size and location, staffing levels and numbers of deliveries per year.
      There were also questions regarding regional and other pain relief methods used
      in labour, ways of administration, drugs used and monitoring of patients.
      RESULTS: The response rate was 24%. Around 45% of responding hospitals had only 1
      3 deliveries per year, which makes it difficult to provide separate obstetric
      anaesthetic cover. Only ten hospitals (11%) employed an anaesthetist for the
      labour ward. Epidural analgesia was used in 55% of hospitals but only 20%
      provided the service for 24 hours per day and free of charge. Entonox was used
      very occasionally, but the most common means of pain relief was pethidine
      injection. There were marked differences in the medication used for labour
      epidurals, with 18% of units using high concentrations of local anaesthetics
      which could result in motor block. Despite a lack of regulations in Polish law
      and a lack of proper training in 50% of units, midwives were looking after the
      patients with established labour epidural which could create medico-legal
      consequences. There was also a marked variation in the parameters monitored
      during labour analgesia. CONCLUSION: Epidural labour analgesia was offered for 24
      hours per day and free of charge in only 20% of hospitals. Without public
      pressure it will be difficult to get more funding from the National Health Fund
      (NFZ) to enable other hospitals, especially those with small obstetric units, to
      introduce regional labour analgesia. Although the 2009 guidelines addressed most
      of the issues regarding the conduct of epidural labour analgesia, changes need to
      be made in Polish law to allow midwives to be appropriately trained to look after
      parturients with regional labour analgesia.

PMID- 24092512
TI  - The Clarus Video System stylet for awake intubation in a very difficult urgent
      intubation.
AB  - Awake fibreoptic intubation (AFI) is a standard method of airway management in a
      case of anticipated difficult intubation. It is usually performed using flexible
      fibroscopes. In this report, we describe the case of a 42 year-old female patient
      who suffered from congenital disease producing severe deformation of the head,
      face, neck and chest. In this case, the AFI procedure was performed successfully
      using a rigid intubation stylet: the Clarus Video System. One of the advantages
      of rigid stylets is that they are very easy to use, and in the hands of
      anaesthesiologists not very familiar with fibroscope intubation, they can be an
      alternative to flexible fibroscopes in AFI procedures. 

PMID- 24092513
TI  - Perioperative management of cardiac surgery patients who are at the risk of acute
      kidney injury.
AB  - Acute kidney injury is one of the most frequent and clinically important of all
      postoperative complications in cardiac surgery. It is estimated that almost half
      of subjects suffer from a deterioration of kidney function after a cardio
      pulmonary by-pass. Renal insufficiency impacts upon the outcome in terms of an
      increase in postoperative morbidity and mortality, and a decrease in quality of
      life. Recently, a modified and unified classification of cardio-renal syndrome
      has been devised, which takes into account bilateral association between the
      heart and the kidneys. Because acute decompensation in heart function leads to
      acute kidney damage, therefore cardiac surgery-associated acute kidney injury may
      be recognised as a type 1 cardio-renal syndrome from a pathophysiological point
      of view. This paper aims to review the current data on the diagnosis of acute
      kidney injury and preventive strategies that can be implemented in cardiac
      surgery perioperative care. 

PMID- 24092514
TI  - Ventilator-associated lung injury.
AB  - Mechanical ventilation of disease-affected lungs, as well as being an inadequate
      mode of ventilation for initially healthy lungs, can cause significant changes in
      their structure and function. In order to differentiate these processes, two
      terms are used: ventilator-associated lung injury (VALI) and ventilator-induced
      lung injury (VILI). In both cases, lung injury primarily results from differences
      in transpulmonary pressure - a consequence of an imbalance between lung stress
      and strain. This paper focuses on changes in lung structure and function due to
      this imbalance. Moreover, in this context, barotrauma, volutrauma and
      atelectrauma are interpreted, and the importance of signal transduction as a
      process inducing local and systemic inflammatory responses (biotrauma), is
      determined. None of the assessed methods of reducing VALI and VILI has been found
      to be entirely satisfactory, yet studies evaluating oscillatory ventilation,
      liquid ventilation, early ECMO, super-protective ventilation or noisy ventilation
      and administration of certain drugs are under way. Low tidal volume ventilation
      and adequately adjusted PEEP appear to be the best preventive measures of
      mechanical ventilation in any setting, including the operating theatre.
      Furthermore, this paper highlights the advances in VILI/VALI prevention resulting
      from better understanding of pathophysiological phenomena. 

PMID- 24092515
TI  - Methods of central vascular access for haemodialysis.
AB  - The basic form of renal replacement therapy is haemodialysis. The duration and
      efficacy of this treatment depends on well-functioning vascular access. Short
      term or long-term catheters are used if the arterial-venous fistula placement is
      not possible or not indicated. According to the recommendations of the NKF DOQI
      (National Kidney Foundation Disease Outcomes Quality Initiative), the first
      choice of access is the right internal jugular vein, and the next are the left
      internal jugular, femoral and subclavian vein. In this article, we present
      approaches to the abovementioned veins for haemodialysis cathether insertion as
      well as catheter tip positioning in the venous system to prevent serious
      complications. 

PMID- 24092516
TI  - Ultrasound in critical care.
AB  - Ultrasound has been revolutionising our specialty. The introduction of new,
      portable machines and goal-directed protocols has led many anaesthetists to use
      this diagnostic tool in their daily practice. Immediate, bedside ultrasound
      diagnosis of many life-threatening emergencies (pneumothorax, cardiac tamponade,
      or internal haemorrhage) enables not only the institution of proper treatment,
      but also the monitoring of its effectiveness. Ultrasound guided invasive
      procedures (such as vascular cannulations, toraco- and pericardiocentesis) have
      superseded the old anatomical landmarks-based techniques due to a greater safety
      margin. In order to perform a credible ultrasound examination, a proper level of
      competence is required. In this review article, the authors present various
      critical ultrasound applications. 

PMID- 24092517
TI  - A qualitative analysis of bariatric patients' post-surgical barriers to exercise.
AB  - Research has shown that some bariatric patients overestimate post-surgical
      exercise levels, while others struggle with negative cognitions and follow
      through on intentions to exercise; however, little exists on specific barriers
      affecting bariatric patients' post-surgical exercise behaviors. Considering that
      regular exercise is a predictor of weight loss maintenance, further research is
      warranted. Survey methodology was utilized to assess post-operative exercise
      barriers as well as beneficial post-surgical exercise services among a sample of
      bariatric patients solicited from an online support website. Qualitative
      assessment of responses was completed using inductive content analysis. Higher
      order themes for exercise barriers included internal, external, and no barriers;
      generic categories determined for internal barriers included motivational and
      physical barriers. Of the participants, 78% reported at least one internal
      motivational barrier, and the most frequently reported subcategorical barrier was
      time (28%); physical barriers were reported related to surgery (9%) or other
      chronic conditions (19%). Higher-order themes for exercise services included
      positive descriptions such as benefits from exercise prescription as well as the
      importance of facilities and individuals, while negative descriptions included no
      services available or services that were unhelpful. Participants cited the
      benefit of community-based facilities, so providers might consider partnering
      with local professionals to deliver exercise services. Staff should be aware of
      physical barriers specific to bariatric populations including issues with post
      surgical stamina and chronic comorbid conditions in order to provide appropriate
      exercise prescription. In addition, as motivational and time barriers occur
      frequently, providers should be well-trained on how to help patients overcome
      these impediments to exercise maintenance.

PMID- 24092518
TI  - Analysis of antioxidant and anti-inflammatory activity of silicon in murine
      macrophages.
AB  - The purpose of this study is to investigate the antioxidant and anti-inflammatory
      properties of silicon (Si) in the RAW 264.7 murine macrophage cell line.
      Lipopolysaccharide (LPS) was used to induce inflammatory conditions, and cells
      were treated with 0, 1, 5, 10, 25, 50, and 100 MUM Si in the form of sodium
      metasilicate. Tert-butylhydroquinone (TBHQ), a well-known antioxidative
      substance, was used as a positive control to assess the degree of antioxidative
      and anti-inflammatory properties of Si. Sodium metasilicate at 100 MUM suppressed
      LPS-induced nitric oxide generation from macrophages 36 h after treatment. In
      addition, 50 MUM sodium metasilicate decreased interleukin-6 production, and the
      degree of suppression was comparable to that of 10 MUM TBHQ treatment. LPS
      induced messenger RNA (mRNA) expression of tumor necrosis factor-alpha and
      inducible nitric oxide synthase was significantly decreased by 1, 5, 10, and 50
      MUM sodium metasilicate. Cyclooxygenase-2 mRNA expression was also suppressed by
      1, 5, 25, and 50 MUM sodium metasilicate. Based on these data, Si has the ability
      to suppress the production of inflammatory cytokines and mediators, possibly
      through the suppression of radical scavenger activity and down-regulation of gene
      expression of inflammatory mediators.

PMID- 24092520
TI  - Polycystic kidney disease and chronic renal failure in tuberous sclerosis.
AB  - Tuberous sclerosis is a rare genetic disease which leads to formation of benign
      tumours in the brain and other organs of the body. It is a multisystem disease
      with various clinical manifestations. Renal angiomyolipomas are the most common
      renal manifestations whereas renal cell carcinoma is the least. Renal cysts are
      found in around 20% of the patients but polycystic kidney disease is present in
      less than 2% cases and is relatively rare manifestation of the disease. We
      present a case of tuberous sclerosis in a 60-year-old man who presented to the
      medicine outpatient department for routine evaluation of his hypertension. He was
      diagnosed as tuberous sclerosis. His ultrasound and CT scan of abdomen revealed
      polycystic kidney disease. His kidney function test and urine analysis were
      suggestive of chronic kidney disease. 

PMID- 24092521
TI  - Cancer mortality among psychiatric patients treated in a community-based system
      of care: a 25-year case register study.
AB  - PURPOSE: Cancer mortality data allow assessing, at the same time, the risk of
      developing the disease and the quality of care provided to patients after the
      oncologic diagnosis. This study explores the risk of death caused by a single
      tumor site in a psychiatric population treated in a community-based psychiatric
      service. METHODS: All patients with an ICD-10 psychiatric diagnosis, seeking care
      in 1982-2006 (25 years), were included. Data were drawn from the South Verona
      Psychiatric Case Register (PCR). Mortality and cause of death were ascertained
      using different procedures and sources. Standardized mortality ratios (SMRs) were
      used to compare the observed number of deaths with the expected number using as
      reference a population in the Veneto region. RESULTS: Having been admitted to the
      hospital (SMR = 1.32), having a short interval from registration (1.52), having a
      diagnosis of alcoholism (2.03), and being a middle-aged male (1.83) were factors
      showing an increased risk of death from cancer. Increased SMRs were found for
      cancer of the oral cavity (22.93), lymphoma, leukemias, Hodgkin's lymphoma
      (8.01), and central nervous system (CNS) and cranial nerve tumors (4.75). The SMR
      decreased for stomach tumors (0.49). Patients with alcoholism (5.90 for larynx),
      affective disorders (20.00 for lymphomas), and personality disorders (28.00 for
      SNC) were found to be exposed to a high risk of cancer death in specific sites.
      CONCLUSIONS: Psychiatric patients showed different patterns of site-specific
      cancer mortality when compared with the general population. The 20-fold higher
      risk of dying from hematological neoplasms needs further investigation. Chronic
      use of phenothiazines could be involved in the relative protection from stomach
      and prostate cancer found in psychiatric patients.

PMID- 24092522
TI  - Development and characterization of lyophilized diazepam-loaded polymeric
      micelles.
AB  - Polymeric micelles were studied as delivery carriers of diazepam, a practically
      insoluble drug in water, for rectal administration. The diazepam-loaded polymeric
      micelles were developed by using poloxamer 407 (P407), poloxamer 188, and D-alpha
      tocopheryl poly(ethylene glycol) 1000 succinate (TPGS). Among the used polymers,
      TPGS resulted in polymeric micelles with good characteristics for encapsulation
      of diazepam which had the small particle size of 8-12 nm and narrow size
      distribution (PI 0.053-0.275). Additionally, 7.5% w/v of TPGS could entirely
      entrap the desired concentration of diazepam (5 mg/mL). To improve the physical
      stability upon lyophilization, an addition of P407 of 1% w/v prevented
      aggregation, increased physical stability, and maintained chemical stability of
      the lyophilized powders of diazepam-loaded polymeric micelles for 3 months
      storage at 4 degrees C. The rate and amount of diazepam release from TPGS
      polymeric micelles mainly depended on the concentration of TPGS. The release data
      were fitted to Higuchi's model suggesting that the drug release mechanism was
      controlled by Fickian diffusion. In conclusion, 10% w/v TPGS and 1% w/v P407 were
      the optimum formulation of lyophilized diazepam-loaded polymeric micelles.

PMID- 24092523
TI  - The effect of moisture on the flowability of pharmaceutical excipients.
AB  - The effect of moisture content on flowability of six pharmaceutical powders
      (microcrystalline cellulose (MCC), hydroxypropyl methylcellulose (HPMC),
      carboxymethyl cellulose (CMC), polyvinylpyrrolidone (PVP), corn starch, and
      potato starch) was investigated. Powder flowability was measured using
      established static techniques and emerging dynamic avalanche behavior
      measurements. Static techniques did not provide enough resolution to clearly
      identify changes in flowability due to increasing powder moisture content.
      Avalanche time and its standard deviation showed that flowability of MCC, CMC,
      PVP, and potato starch decreased after a critical moisture content, flowability
      of corn starch increased and flowability did not significantly change for HPMC.
      The moisture decreased flowability by forming stronger interparticle liquid
      bridges and increased flowability by acting as a lubricant. The dynamic density
      of the celluloses and PVP decreased linearly with increasing moisture content as
      the particles swelled with water. The starches also swelled and decreased in
      dynamic density, but only after a moisture content corresponding to monolayer
      coverage of water around the particles was reached. As flowability and dynamic
      density change with moisture content, to ensure consistent production of high
      quality tablets, the moisture content of the powders must be measured and
      controlled.

PMID- 24092524
TI  - PhonItalia: a phonological lexicon for Italian.
AB  - In this article, we present the first open-access lexical database that provides
      phonological representations for 120,000 Italian word forms. Each of these also
      includes syllable boundaries and stress markings and a comprehensive range of
      lexical statistics. Using data derived from this lexicon, we have also generated
      a set of derived databases and provided estimates of positional frequency use for
      Italian phonemes, syllables, syllable onsets and codas, and character and phoneme
      bigrams. These databases are freely available from phonitalia.org. This article
      describes the methods, content, and summarizing statistics for these databases.
      In a first application of this database, we also demonstrate how the distribution
      of phonological substitution errors made by Italian aphasic patients is related
      to phoneme frequency.

PMID- 24092525
TI  - Psychosocial interventions for people with both severe mental illness and
      substance misuse.
AB  - BACKGROUND: Even low levels of substance misuse by people with a severe mental
      illness can have detrimental effects. OBJECTIVES: To assess the effects of
      psychosocial interventions for reduction in substance use in people with a
      serious mental illness compared with standard care. SEARCH METHODS: For this
      update (2013), the Trials Search Co-ordinator of the Cochrane Schizophrenia Group
      (CSG) searched the CSG Trials Register (July 2012), which is based on regular
      searches of major medical and scientific databases. The principal authors
      conducted two further searches (8 October 2012 and 15 January 2013) of the
      Cochrane Database of Systematic Reviews, MEDLINE and PsycINFO. A separate search
      for trials of contingency management was completed as this was an additional
      intervention category for this update. SELECTION CRITERIA: We included all
      randomised controlled trials (RCTs) comparing psychosocial interventions for
      substance misuse with standard care in people with serious mental illness. DATA
      COLLECTION AND ANALYSIS: We independently selected studies, extracted data and
      appraised study quality. For binary outcomes, we calculated standard estimates of
      relative risk (RR) and their 95% confidence intervals (CI) on an intention-to
      treat basis. For continuous outcomes, we calculated the mean difference (MD)
      between groups. For all meta-analyses we pooled data using a random-effects
      model. Using the GRADE approach, we identified seven patient-centred outcomes and
      assessed the quality of evidence for these within each comparison. MAIN RESULTS:
      We included 32 trials with a total of 3165 participants. Evaluation of long-term
      integrated care included four RCTs (n = 735). We found no significant differences
      on loss to treatment (n = 603, 3 RCTs, RR 1.09 CI 0.82 to 1.45, low quality of
      evidence), death by 3 years (n = 421, 2 RCTs, RR 1.18 CI 0.39 to 3.57, low
      quality of evidence), alcohol use (not in remission at 36 months) (n = 143, 1
      RCT, RR 1.15 CI 0.84 to 1.56,low quality of evidence), substance use (n = 85, 1
      RCT, RR 0.89 CI 0.63 to 1.25, low quality of evidence), global assessment of
      functioning (n = 171, 1 RCT, MD 0.7 CI 2.07 to 3.47, low quality of evidence), or
      general life satisfaction (n = 372, 2 RCTs, MD 0.02 higher CI 0.28 to 0.32,
      moderate quality of evidence).For evaluation of non-integrated intensive case
      management with usual treatment (4 RCTs, n = 163) we found no statistically
      significant difference for loss to treatment at 12 months (n = 134, 3 RCTs, RR
      1.21 CI 0.73 to 1.99, very low quality of evidence).Motivational interviewing
      plus cognitive behavioural therapy compared to usual treatment (7 RCTs, total n =
      878) did not reveal any advantage for retaining participants at 12 months (n =
      327, 1 RCT, RR 0.99 CI 0.62 to 1.59, low quality of evidence) or for death (n =
      493, 3 RCTs, RR 0.72 CI 0.22 to 2.41, low quality of evidence), and no benefit
      for reducing substance use (n = 119, 1 RCT, MD 0.19 CI -0.22 to 0.6, low quality
      of evidence), relapse (n = 36, 1 RCT, RR 0.5 CI 0.24 to 1.04, very low quality of
      evidence) or global functioning (n = 445, 4 RCTs, MD 1.24 CI 1.86 to 4.34, very
      low quality of evidence).Cognitive behavioural therapy alone compared with usual
      treatment (2 RCTs, n = 152) showed no significant difference for losses from
      treatment at 3 months (n = 152, 2 RCTs, RR 1.12 CI 0.44 to 2.86, low quality of
      evidence). No benefits were observed on measures of lessening cannabis use at 6
      months (n = 47, 1 RCT, RR 1.30 CI 0.79 to 2.15, very low quality of evidence) or
      mental state (n = 105, 1 RCT, Brief Psychiatric Rating Scale MD 0.52 CI -0.78 to
      1.82, low quality of evidence).We found no advantage for motivational
      interviewing alone compared with usual treatment (8 RCTs, n = 509) in reducing
      losses to treatment at 6 months (n = 62, 1 RCT, RR 1.71 CI 0.63 to 4.64, very low
      quality of evidence), although significantly more participants in the
      motivational interviewing group reported for their first aftercare appointment (n
      = 93, 1 RCT, RR 0.69 CI 0.53 to 0.9). Some differences, favouring treatment, were
      observed in abstaining from alcohol (n = 28, 1 RCT, RR 0.36 CI 0.17 to 0.75, very
      low quality of evidence) but not other substances (n = 89, 1 RCT, RR -0.07 CI 
      0.56 to 0.42, very low quality of evidence), and no differences were observed in
      mental state (n = 30, 1 RCT, MD 0.19 CI -0.59 to 0.21, very low quality of
      evidence).We found no significant differences for skills training in the numbers
      lost to treatment by 12 months (n = 94, 2 RCTs, RR 0.70 CI 0.44 to 1.1, very low
      quality of evidence).We found no differences for contingency management compared
      with usual treatment (2 RCTs, n = 206) in numbers lost to treatment at 3 months
      (n = 176, 1 RCT, RR 1.65 CI 1.18 to 2.31, low quality of evidence), number of
      stimulant positive urine tests at 6 months (n = 176, 1 RCT, RR 0.83 CI 0.65 to
      1.06, low quality of evidence) or hospitalisations (n = 176, 1 RCT, RR 0.21 CI
      0.05 to 0.93, low quality of evidence).We were unable to summarise all findings
      due to skewed data or because trials did not measure the outcome of interest. In
      general, evidence was rated as low or very low due to high or unclear risks of
      bias because of poor trial methods, or poorly reported methods, and imprecision
      due to small sample sizes, low event rates and wide confidence intervals.
      AUTHORS' CONCLUSIONS: We included 32 RCTs and found no compelling evidence to
      support any one psychosocial treatment over another for people to remain in
      treatment or to reduce substance use or improve mental state in people with
      serious mental illnesses. Furthermore, methodological difficulties exist which
      hinder pooling and interpreting results. Further high quality trials are required
      which address these concerns and improve the evidence in this important area.

PMID- 24092526
TI  - Suicide and the surrogate.

PMID- 24092527
TI  - Approaches for neural tissue regeneration.
AB  - There is currently no treatment for neurodegenerative diseases such as
      Parkinson's or Alzheimer's diseases. While spinal cord injury has no treatment
      either, nerve injuries are being treated with autologous grafts, a procedure that
      in turn translates into a loss of function in the donor area. The development of
      therapies for these pathologies has become urgent as population keeps on ageing.
      A promising direction of investigation is the use of regenerative techniques to
      re-grow healthy and functional tissue in the injured area. In this review
      article, various approaches currently investigated to promote neural regeneration
      are covered. Those include approaches based on (and many times combining) stem
      cell therapy, scaffolds made of hydrogel, electrospun fibers and conductive
      materials as well as the use of soluble or non-diffusible growth factors. 

PMID- 24092528
TI  - Isolation of side population cells from endometrial cancer cells using a violet
      laser diode.
AB  - Cancer stem cells (CSCs) possess the ability for self-renewal, differentiation,
      and tumorigenesis and play a role in cancer recurrence and metastasis. CSCs are
      usually sorted in analysis into side population (SP) cells using ultraviolet (UV)
      laser (350 nm) excitation; they cannot be stained with Hoechst 33342 because of
      their efflux ability. However, it is difficult to avoid cell damage using a UV
      laser. Therefore, we attempted to isolate CSCs using a violet laser (407 nm)
      excitation to avoid cellular DNA damage. We sorted SP cells and main population
      (MP) cells from a human endometrial cancer cell line using the FACSAria system
      equipped with a violet laser and analyzed the biological properties of these
      cells. SP cells exhibited drug efflux, self-renewal, differentiation abilities,
      and tumorigenicity. It was found that v-Ki-ras2 Kirsten rat sarcoma viral
      oncogene homolog (KRAS) expression was significantly higher in SP cells than in
      MP cells. Our results suggest that CSCs exist in the SP fraction sorted using the
      FACSAria system equipped with a violet laser, which presents a useful tool to
      isolate small populations of viable putative CSCs from solid tumors and can be
      used to identify and characterize CSCs.

PMID- 24092529
TI  - Strategies for partner notification for sexually transmitted infections,
      including HIV.
AB  - BACKGROUND: Partner notification (PN) is the process whereby sexual partners of
      an index patient are informed of their exposure to a sexually transmitted
      infection (STI) and the need to obtain treatment. For the person (index patient)
      with a curable STI, PN aims to eradicate infection and prevent re-infection. For
      sexual partners, PN aims to identify and treat undiagnosed STIs. At the level of
      sexual networks and populations, the aim of PN is to interrupt chains of STI
      transmission. For people with viral STI, PN aims to identify undiagnosed
      infections, which can facilitate access for their sexual partners to treatment
      and help prevent transmission. OBJECTIVES: To assess the effects of different PN
      strategies in people with STI, including human immunodeficiency virus (HIV)
      infection. SEARCH METHODS: We searched electronic databases (the Cochrane Central
      Register of Controlled Trials (CENTRAL), MEDLINE and EMBASE) without language
      restrictions. We scanned reference lists of potential studies and previous
      reviews and contacted experts in the field. We searched three trial registries.
      We conducted the most recent search on 31 August 2012. SELECTION CRITERIA:
      Published or unpublished randomised controlled trials (RCTs) or quasi-RCTs
      comparing two or more PN strategies. Four main PN strategies were included:
      patient referral, expedited partner therapy, provider referral and contract
      referral. Patient referral means that the patient notifies their sexual partners,
      either with (enhanced patient referral) or without (simple patient referral)
      additional verbal or written support. In expedited partner therapy, the patient
      delivers medication or a prescription for medication to their partner(s) without
      the need for a medical examination of the partner. In provider referral, health
      service personnel notify the partners. In contract referral, the index patient is
      encouraged to notify partner, with the understanding that the partners will be
      contacted if they do not visit the health service by a certain date. DATA
      COLLECTION AND ANALYSIS: We analysed data according to paired partner referral
      strategies. We organised the comparisons first according to four main PN
      strategies (1. enhanced patient referral, 2. expedited partner therapy, 3.
      contract referral, 4. provider referral). We compared each main strategy with
      simple patient referral and then with each other, if trials were available. For
      continuous outcome measures, we calculated the mean difference (MD) with 95%
      confidence intervals (CI). For dichotomous variables, we calculated the risk
      ratio (RR) with 95% CI. We performed meta-analyses where appropriate. We
      performed a sensitivity analysis for the primary outcome re-infection rate of the
      index patient by excluding studies with attrition of greater than 20%. Two review
      authors independently assessed the risk of bias and extracted data. We contacted
      study authors for additional information. MAIN RESULTS: We included 26 trials
      (17,578 participants, 9015 women and 8563 men). Five trials were conducted in
      developing countries. Only two trials were conducted among HIV-positive patients.
      There was potential for selection bias, owing to the methods of allocation used
      and of performance bias, owing to the lack of blinding in most included studies.
      Seven trials had attrition of greater than 20%, increasing the risk of bias.The
      review found moderate-quality evidence that expedited partner therapy is better
      than simple patient referral for preventing re-infection of index patients when
      combining trials of STIs that caused urethritis or cervicitis (6 trials; RR 0.71,
      95% CI 0.56 to 0.89, I(2) = 39%). When studies with attrition greater than 20%
      were excluded, the effect of expedited partner therapy was attenuated (2 trials;
      RR 0.8, 95% CI 0.62 to 1.04, I(2) = 0%). In trials restricted to index patients
      with chlamydia, the effect was attenuated (2 trials; RR 0.90, 95% CI 0.60 to
      1.35, I(2) = 22%). Expedited partner therapy also increased the number of
      partners treated per index patient (three trials) when compared with simple
      patient referral in people with chlamydia or gonorrhoea (MD 0.43, 95% CI 0.28 to
      0.58) or trichomonas (MD 0.51, 95% CI 0.35 to 0.67), and people with any STI
      syndrome (MD 0.5, 95% CI 0.34 to 0.67). Expedited partner therapy was not
      superior to enhanced patient referral in preventing re-infection (3 trials; RR
      0.96, 95% CI 0.60 to 1.53, I(2) = 33%, low-quality evidence). Home sampling kits
      for partners (four trials) did not result in lower rates of re-infection in the
      index case (measured in one trial), or higher numbers of partners elicited (three
      trials), notified (two trials) or treated (one trial) when compared with simple
      patient referral. There was no consistent evidence for the relative effects of
      provider, contract or other patient referral methods. In one trial among men with
      non-gonococcal urethritis, more partners were treated with provider referral than
      with simple patient referral (MD 0.5, 95% CI 0.37 to 0.63). In one study among
      people with syphilis, contract referral elicited treatment of more partners than
      provider referral (MD 2.2, 95% CI 1.95 to 2.45), but the number of partners
      receiving treatment was the same in both groups. Where measured, there was no
      statistical evidence of differences in the incidence of adverse effects between
      PN strategies. AUTHORS' CONCLUSIONS: The evidence assessed in this review does
      not identify a single optimal strategy for PN for any particular STI. When
      combining trials of STI causing urethritis or cervicitis, expedited partner
      therapy was more successful than simple patient referral for preventing re
      infection of the index patient but was not superior to enhanced patient referral.
      Expedited partner therapy interventions should include all components that were
      part of the trial intervention package. There was insufficient evidence to
      determine the most effective components of an enhanced patient referral strategy.
      There are too few trials to allow consistent conclusions about the relative
      effects of provider, contract or other patient referral methods for different
      STIs. More high-quality RCTs of PN strategies for HIV and syphilis, using
      biological outcomes, are needed.

PMID- 24092530
TI  - Developmental upregulation of an alternative form of pcp2 with reduced GDI
      activity.
AB  - The pcp2/L7 gene is characterized by its very cell type-specific expression
      restricted to cerebellar Purkinje cells and retinal bipolar neurons. Although
      remarkable progress as to the biochemical properties of the encoded protein has
      been made, knowledge on its physiological functions remains sparse. While
      characterizing a pcp2-driven transgenic strain, we observed the presence of a
      longer, so far unknown, pcp2 transcript. Different from another recently
      discovered splice variant, ret-pcp2, expression of this novel transcript is
      observed in bipolar as well as cerebellar Purkinje cells of mid-postnatal mice.
      The protein encoded by our novel variant appears to be less efficient in binding
      to Galpha subunits compared to the original L7/pcp2 protein and it is also less
      inhibitory with respect to GTPgamma binding. Its expression in the eye appears to
      be independent from eye opening in postnatal mice. 

PMID- 24092531
TI  - Closing the patient-oncologist communication gap: a review of historic and
      current efforts.
AB  - Effective communication is essential in developing any relationship--this is
      particularly true between oncologists and their patients. The patient-oncologist
      relationship is one of the most delicate in medicine, and given the strong
      emotions associated with cancer, successful communication plays a paramount role
      in the wellbeing of patients and oncologists. Significant advances to close the
      communication gap have occurred over the past several decades, largely by
      addressing deficiencies in the various stages of an oncologist's lengthy
      training: undergraduate medical education, residency and fellowship, and
      continuing medical education. Stemming from several milestones achieved by highly
      motivated groups of individuals, including the creation of consensus statements
      and guidelines by communication education experts, progress has been made to
      improve patient-oncologist communication. This progress is marked by the
      development of evidence-based communication skills training programs, such as
      Oncotalk and Comskil, in addition to the creation of distant-learning modalities,
      such as the Studying Communication in Oncologist-Patient Encounters trial. This
      review article outlines the history of communication education during medical
      education and training, and brings to light more recent efforts to promote
      competent, communication-minded physicians necessary for effective cancer care.

PMID- 24092532
TI  - Decisional support throughout the cancer journey for older women diagnosed with
      early stage breast cancer: a single institutional study.
AB  - To determine if older women with early stage breast cancer have sufficient
      decisional support during their breast cancer journey, a questionnaire-based
      study was conducted at the Sunnybrook Odette Cancer Centre, in Toronto, Ontario,
      Canada. Women with stages I and II breast cancer, >=60 years, were contacted upon
      completion of their adjuvant treatment. A questionnaire was developed based on
      focus groups, the literature, and consultation with patients and a
      multidisciplinary team of experts. The questionnaire was divided into six domains
      as follows: (1) information support surrounding diagnosis, (2) impact of cancer
      diagnosis on the patient, (3) quality of interaction with healthcare team, (4)
      decisional support from the healthcare team, (5) additional information needs
      surrounding treatment decision, and (6) information support during radiation
      treatment. Ninety-two of 137 patients approached were included in the analysis.
      Ninety percent were > 60 years at the time of diagnosis and 65% had stage I
      invasive breast cancer. The majority of women received adequate decisional
      support during their cancer journey. Approximately 90% of women indicated that
      they received a high level of support during their cancer diagnosis. We found no
      significant differences in overall decisional support based on age at diagnosis,
      education level, ethnicity, or the presence of co-morbidities. However,
      participants desired additional educational resources such as a worksheet,
      consultation summary, or workbook to assist in making a treatment decision. The
      majority of participants felt that they had sufficient support while making a
      treatment decision for breast cancer.

PMID- 24092533
TI  - Impact of academic and continuing education on oral cancer knowledge, attitude
      and practice among dentists in north-western Italy.
AB  - The present study aims to assess the knowledge, attitude and practice of dentists
      practicing in the Turin Province (north-western Italy) regarding oral cancer
      prevention and early detection, to weigh the impact of academic and continuing
      education and to compare actual and perceived knowledge/practice. A survey was
      prospectively carried out using an anonymous 23-item questionnaire. Bivariate
      analyses, multivariate logistic regression analyses and Spearman's correlation
      analyses examined the overall effect of demographic/background characteristics of
      responders, with particular emphasis on academic and continuing education. The
      responder group was formed by 450 dentists representative of the Turin Province
      Council of Dentists. Both academic and continuing education have a significant
      impact on knowledge, with a significant association between the time elapsed from
      continuing education and the degree of knowledge. Knowledge acquired during
      graduation is seen to significantly weaken in the absence of continuing
      education. The present study highlights the need of both thorough academic
      curricula and compulsory current continuing education. 

PMID- 24092536
TI  - Characterizing metal coordination environments in porous organic polymers: a
      joint density functional theory and experimental infrared spectroscopy study.
AB  - Very POP right now! DFT computational analysis on the structural, energetic, and
      IR spectroscopic characteristics of a porous organic polymer support, [Ta(NMe2 )5
      ] as a molecular precursor, and the catalytic material synthesized from these two
      components are presented and analyzed against recorded IR spectra of these
      systems. The analysis leads to unambiguous identification of the atomic structure
      of the POP-supported Ta-amide reaction center synthesized in the experiment. 

PMID- 24092537
TI  - Colloidal size effect and metal-particle migration in M@MOF/PCP catalysis.
AB  - Metal-organic framework catalysis: MIL-101 crystallites have been synthesized in
      different sizes and infiltrated with the Pd precursor complex [Pd(C5 H5 )(C3 H5
      )]. Reduction of the Pd precursor complex gave rise to Pd nanoparticles inside
      the cavities of MIL-101 crystallites. Catalytic studies showed a clear dependence
      of the catalytic activity on the MIL-101 crystallite size. Furthermore, Pd
      nanoparticle migration from MIL-101 crystallite to crystallite was observed under
      mild conditions. 

PMID- 24092538
TI  - Chiral anion catalysis in the enantioselective 1,4-reduction of the 1
      benzopyrylium ion as a reactive intermediate.
AB  - Anionic! Novel chiral anion catalysis of the enantioselective 1,4-reduction of
      the 1-benzopyrylium ion by a chiral phosphoric acid was accomplished with a
      Hantzsch ester as the reducing agent. The enantioselective reduction established
      is composed of a two-step consecutive transformation involving stereoablative
      loss of the hydroxy group from racemic 2H-chromen-2-ol derivatives to generate
      the achiral 1-benzopyrylium ion as a reactive key intermediate. 

PMID- 24092539
TI  - Rhodium(I)-catalyzed cycloisomerization of nitrogen-tethered indoles and
      alkylidenecyclopropanes: convenient access to polycyclic indole derivatives.
AB  - At the end of its tether: A new synthetic protocol for the preparation of
      polycyclic indole derivatives has been developed from a rhodium(I)-catalyzed
      cycloisomerization of a nitrogen-tethered indole and alkylidenecyclopropane,
      affording the corresponding tetrahydro-beta-carboline derivatives in moderate to
      good yields. Further transformations give a direct and rapid route to tetracyclic
      compounds through transition-metal catalysis. 

PMID- 24092540
TI  - Lipid Segregation in Membranes of Anionic Liposomes Adsorbed onto Polycationic
      Brushes.
AB  - Two-phased: Complexation of liposomes to spherical polycationic brushes induces
      lipid segregation in the liposomal membrane. The greater the initial anionic
      lipid content in the membrane, the more the electroneutral lipid dilutes the
      induced anionic clusters. 

PMID- 24092541
TI  - Regioselective hydroxylation of C(12)-C(15) fatty acids with fluorinated
      substituents by cytochrome P450 BM3.
AB  - We demonstrate herein that wild-type cytochrome P450 BM3 can recognize non
      natural substrates, such as fluorinated C12 -C15 chain-length fatty acids, and
      show better catalysis for their efficient conversion. Although the binding
      affinities for fluorinated substrates in the P450 BM3 pocket are marginally lower
      than those for non-fluorinated substrates, spin-shift measurements suggest that
      fluoro substituents at the omega-position can facilitate rearrangement of the
      dynamic structure of the bulk-water network within the hydrophobic pocket through
      a micro desolvation process to expel the water ligand of the heme iron that is
      present in the resting state. A lowering of the Michaelis-Menten constant (Km ),
      however, indicates that fluorinated fatty acids are indeed better substrates
      compared with their non-fluorinated counterparts. An enhancement of the turnover
      frequencies (kcat ) for electron transfer from NADPH to the heme iron and for C?H
      bond oxidation by compound I (Cpd I) to yield the product suggests that the
      activation energies associated with going from the enzyme-substrate (ES state) to
      the corresponding transition state (ES(?) state) are significantly lowered for
      both steps in the case of the fluorinated substrates. Delicate control of the
      regioselectivity by the fluorinated terminal methyl groups of the C12 -C15 fatty
      acids has been noted. Despite the fact that residues Arg47/Tyr51/Ser72 exert
      significant control over the hydroxylation of the subterminal carbon atoms toward
      the hydrocarbon tail, the fluorine substituent(s) at the omega-position affects
      the regioselective hydroxylation. For substrate hydroxylation, we have found that
      fluorinated lauric acids probably give a better structural fit for the heme
      pocket than fluorinated pentadecanoic acid, even though pentadecanoic acid is by
      far the best substrate among the reported fatty acids. Interestingly, 12
      fluorododecanoic acid, with only one fluorine atom at the terminal methyl group,
      exhibits a comparable turnover frequency to that of pentadecanoic acid. Thus,
      fluorination of the terminal methyl group introduces additional interactions of
      the substrate within the hydrophobic pocket, which influence the electron
      transfers for both dioxygen activation and the controlled oxidation of aliphatics
      mediated by high-valent oxoferryl species. 

PMID- 24092542
TI  - Hydrogen generation by water reduction with [Cp*(2) Ti(OTf)]: identifying
      elemental mechanistic steps by combined in situ FTIR and in situ EPR spectroscopy
      supported by DFT calculations.
AB  - A detailed mechanism of hydrogen production by reduction of water with
      decamethyltitanocene triflate [Cp*2 Ti(III) (OTf)] has been derived for the first
      time, based on a comprehensive in situ spectroscopic study including EPR and ATR
      FTIR spectroscopy supported by DFT calculations. It is demonstrated that two H2 O
      molecules coordinate to [Cp*2 Ti(III) (OTf)] subsequently forming [Cp2 *Ti(III)
      (H2 O)(OTf)] and [Cp*Ti(III) (H2 O)2 (OTf)]. Triflate stabilizes the water
      ligands by hydrogen bonding. Liberation of hydrogen proceeds only from the diaqua
      complex [Cp*Ti(III) (H2 O)2 (OTf)] and involves, most probably, abstraction and
      recombination of two H atoms from two molecules of [Cp*Ti(III) (H2 O)2 (OTf)] in
      close vicinity, which is driven by the formation of a strong covalent Ti?OH bond
      in the resulting final product [Cp*2 Ti(IV) (OTf)(OH)]. 

PMID- 24092544
TI  - Humanities in medicine: preparing for practice.

PMID- 24092543
TI  - PPARalpha activation induces N(epsilon)-Lys-acetylation of rat liver peroxisomal
      multifunctional enzyme type 1.
AB  - Peroxisomes are ubiquitous subcellular organelles that participate in metabolic
      and disease processes, with few of its proteins undergoing posttranslational
      modifications. As the role of lysine-acetylation has expanded into the cellular
      intermediary metabolism, we used a combination of differential centrifugation,
      organelle isolation by linear density gradient centrifugation, western blot
      analysis, and peptide fingerprinting and amino acid sequencing by mass
      spectrometry to investigate protein acetylation in control and ciprofibrate
      treated rat liver peroxisomes. Organelle protein samples isolated by density
      gradient centrifugation from PPARalpha-agonist treated rat liver screened with an
      anti-N(epsilon)-acetyl lysine antibody revealed a single protein band of 75 kDa.
      Immunoprecipitation with this antibody resulted in the precipitation of a protein
      from the protein pool of ciprofibrate-induced peroxisomes, but not from the
      protein pool of non-induced peroxisomes. Peptide mass fingerprinting analysis
      identified the protein as the peroxisomal multifunctional enzyme type 1. In
      addition, mass spectrometry-based amino acid sequencing resulted in the
      identification of unique peptides containing 4 acetylated-Lys residues (K155,
      K173, K190, and K583). This is the first report that demonstrates
      posttranslational acetylation of a peroxisomal enzyme in PPARalpha-dependent
      proliferation of peroxisomes in rat liver.

PMID- 24092545
TI  - Research skills: the neglected competency in tomorrow's 21st-century doctors.

PMID- 24092546
TI  - Dance therapy for schizophrenia.
AB  - BACKGROUND: Dance therapy or dance movement therapy (DMT) is defined as 'the
      psychotherapeutic use of movement as a process which furthers the emotional,
      social, cognitive, and physical integration of the individual'. It may be of
      value for people with developmental, medical, social, physical or psychological
      impairments. Dance therapy can be practiced in mental health rehabilitation
      units, nursing homes, day care centres and incorporated into disease prevention
      and health promotion programmes. OBJECTIVES: To evaluate the effects of dance
      therapy for people with schizophrenia or schizophrenia-like illnesses compared
      with standard care and other interventions. SEARCH METHODS: We updated the
      original July 2007 search of the Cochrane Schizophrenia Group' register in July
      2012. We also searched Chinese main medical databases. SELECTION CRITERIA: We
      included one randomised controlled trial (RCT) comparing dance therapy and
      related approaches with standard care or other psychosocial interventions for
      people with schizophrenia. DATA COLLECTION AND ANALYSIS: We reliably selected,
      quality assessed and extracted data. For continuous outcomes, we calculated a
      mean difference (MD); for binary outcomes we calculated a fixed-effect risk ratio
      (RR) and their 95% confidence intervals (CI). We created a 'Summary of findings'
      table using the GRADE approach. MAIN RESULTS: We included one single blind study
      (total n = 45) of reasonable quality. It compared dance therapy plus routine care
      with routine care alone. Most people tolerated the treatment package but nearly
      40% were lost in both groups by four months (1 RCT n = 45, RR 0.68 95% CI 0.31 to
      1.51, low quality evidence). The Positive and Negative Syndrome Scale (PANSS)
      average endpoint total scores were similar in both groups (1 RCT n = 43, MD -0.50
      95% CI -11.80 to 10.80, moderate quality evidence) as were the positive sub
      scores (1 RCT n = 43, MD 2.50 CI -0.67 to 5.67, moderate quality evidence). At
      the end of treatment, significantly more people in the dance therapy group had a
      greater than 20% reduction in PANSS negative symptom score (1 RCT n = 45, RR 0.62
      CI 0.39 to 0.97, moderate quality evidence), and overall, average negative
      endpoint scores were lower (1 RCT n = 43, MD -4.40 CI -8.15 to -0.65, moderate
      quality evidence). There was no difference in satisfaction score (average
      Client's Assessment of Treatment Scale (CAT) score, 1 RCT n = 42, MD 0.40 CI 
      0.78 to 1.58, moderate quality evidence) and quality of life data were also
      equivocal (average Manchester Short Assessment of Quality of life (MANSA) score,
      1 RCT n = 39, MD 0.00 CI -0.48 to 0.48, moderate quality evidence).  AUTHORS'
      CONCLUSIONS: Based on predominantly moderate quality data, there is no evidence
      to support - or refute - the use of dance therapy in this group of people. This
      therapy remains unproven and those with schizophrenia, their carers, trialists
      and funders of research may wish to encourage future work to increase high
      quality evidence in this area.

PMID- 24092547
TI  - Inflammatory adipokines contribute to insulin resistance in active acromegaly and
      respond differently to different treatment modalities.
AB  - BACKGROUND: Active acromegaly is associated with insulin resistance, but it is
      uncertain whether inflammation in adipose tissue is a contributing factor. AIM:
      To test if GH/IGF1 promotes inflammation in adipocytes, and if this is relevant
      for systemic insulin resistance in acromegaly. Furthermore, to investigate the
      effect of treatment modalities (transsphenoidal surgery (TS), somatostatin
      analogs (SAs), and pegvisomant (PGV)) on glucose metabolism and inflammatory
      biomarkers in acromegaly. METHODS: The in vitro effects of GH/IGF1 on gene
      expression of adipokines in human adipocytes were investigated. Body composition,
      glucose metabolism, and circulating adipokines (adiponectin (AD), high-molecular
      weight AD (HMWAD), leptin, vascular endothelial growth factor-A (VEGF-A),
      monocyte chemotactic protein 1 (MCP1), and thioredoxin (TRX)) were measured in 37
      patients with active acromegaly before and after treatment. RESULTS: In vitro GH,
      but not IGF1, increased VEGF and MCP1 in human adipocytes. In all treatment
      groups, body fat increased and IGF1 decreased to the same extent. Fasting glucose
      decreased in the TS (P=0.016) and PGV (P=0.042) groups, but tended to increase in
      the SA group (P=0.078). Insulin and HOMA-IR decreased in both TS and SA groups,
      while the PGV group showed no changes. Serum VEGF and MCP1 decreased
      significantly in the TS group only (P=0.010, P=0.002), while HMWAD increased with
      PGV treatment only (P=0.018). A multivariate analysis model identified the
      changes in GH and VEGF as predictors of improvement in HOMA-IR after treatment
      (R2=0.39, P=0.002). CONCLUSIONS: i) GH directly promotes inflammation of human
      adipocytes by increasing VEGF and MCP1 levels; ii) glucose metabolism and
      inflammation (VEGF and MCP1) improve to some extent after treatment, despite an
      increase in adipose tissue mass; and iii) the decrease in insulin resistance
      after therapy in acromegaly depends, to some extent, on treatment modalities.

PMID- 24092548
TI  - Adoptive regulatory T-cell therapy preserves systemic immune homeostasis after
      cerebral ischemia.
AB  - BACKGROUND AND PURPOSE: Cerebral ischemia has been shown to result in peripheral
      inflammatory responses followed by long-lasting immunosuppression. Our recent
      study demonstrated that intravenous delivery of regulatory T cells (Tregs)
      markedly protected against transient cerebral ischemia by suppressing neutrophil
      derived matrix metallopeptidase 9 production in the periphery. However, the
      effect of Tregs on systemic inflammatory responses and immune status has not been
      fully characterized. METHODS: Cerebral ischemia was induced by middle cerebral
      artery occlusion for 60 minutes in mice or 120 minutes in rats. Tregs were
      isolated from donor animals by CD4 and CD25 double selection and transferred
      intravenously to ischemic recipients at 2 hours after middle cerebral artery
      occlusion. Animals were euthanized on different days after reperfusion. The
      effects of Tregs on systemic inflammation and immune status were evaluated using
      flow cytometry, ELISAs, and immunohistochemistry. RESULTS: Systemic
      administration of purified Tregs raises functional Tregs in the blood and
      peripheral organs, including spleen and lymph nodes. These exogenous Tregs remain
      in the blood and peripheral organs for >=12 days. Functionally, Treg adoptive
      transfer markedly inhibits middle cerebral artery occlusion-induced elevation of
      inflammatory cytokines (interleukin-6 and tumor necrosis factor alpha) in the
      blood. Furthermore, Treg treatment corrects long-term lymphopenia and improves
      cellular immune functions after ischemic brain injury. As a result, Treg-treated
      animals exhibit decreased bacterial loads in the blood during recovery from
      cerebral ischemic attack. CONCLUSIONS: Treg treatment did not exacerbate
      poststroke immunosuppression. On the contrary, Treg-treated animals displayed
      improved immune status after focal cerebral ischemia.

PMID- 24092549
TI  - Can DWI-ASPECTS substitute for lesion volume in acute stroke?
AB  - BACKGROUND AND PURPOSE: The extent of diffusion lesion on pretreatment imaging is
      a risk factor for poor outcome and hemorrhagic transformation after thrombolysis,
      and volumes of 70 to 100 mL have been advocated as cut-offs. However, estimating
      diffusion-weighted imaging (DWI) lesion volume (VolDWI) in the acute setting may
      be cumbersome. We aimed to determine whether the DWI-Alberta Stroke Program Early
      CT Score (DWI-ASPECTS) can substitute for VolDWI. METHODS: DWI-ASPECTS and VolDWI
      were measured retrospectively on pretreatment MRI (median onset-to-MRI delay=122
      minutes) in 330 consecutively treated patients with middle cerebral artery
      stroke. RESULTS: DWI-ASPECTS and VolDWI were strongly correlated (rho=-0.82), but
      each DWI-ASPECTS point corresponded to a wide range of VolDWI. All patients with
      DWI-ASPECTS>=7 (n=207) had VolDWI<70 mL, whereas 32 of the 34 patients with DWI
      ASPECTS<4 had VolDWI>100 mL. However, intermediate DWI-ASPECTS (4-6; n=89)
      corresponded to highly variable VolDWI (median, 66 mL; interquartile range, 40
      98). CONCLUSIONS: Although each DWI-ASPECTS point corresponds to a wide range of
      volumes, DWI-ASPECTS<4 or >=7 may be used as reliable surrogates of VolDWI>100 or
      <70 mL, respectively.

PMID- 24092551
TI  - Transition of European Cooperative Acute Stroke Study III results to clinical
      practice: ninety-day outcomes in a US cohort.
AB  - BACKGROUND AND PURPOSE: The European Cooperative Acute Stroke Study (ECASS) III
      showed benefit of intravenous tissue-type plasminogen activator for acute
      ischemic stroke 3 to 4.5 hours from onset in selected patients from Europe, with
      this extended treatment subsequently recommended by the American Stroke
      Association. We prospectively enrolled patients with acute ischemic stroke
      treated with intravenous tissue-type plasminogen activator, during the time this
      recommendation was being applied in clinical practice to determine safety and
      efficacy in a representative cohort from the United States. METHODS: Patients
      with acute ischemic stroke treated with intravenous tissue-type plasminogen
      activator were enrolled at 18 primary stroke centers throughout Maryland,
      including community hospitals and academic medical centers. Patients grouped by
      time to treatment (<=3 versus 3-4.5 hours) were compared for the presence of
      exclusion criteria from ECASS III that are not standard practice in the United
      States for <=3 hours (age, >80 years; history of stroke and diabetes mellitus;
      oral anticoagulant treatment; and National Institutes of Health Stroke Scale,
      >25). Outcomes included good function at 90 days (modified Rankin Scale, 0-1 and
      0-2), mortality, and symptomatic intracerebral hemorrhage. RESULTS: In the 3- to
      4.5-hour treatment group, there were significantly fewer patients aged>80 years
      and no patients with the combination of stroke and diabetes mellitus. There were
      no statistically significant differences by time to treatment in symptomatic
      intracerebral hemorrhage, mortality, or functional outcome. CONCLUSIONS: For
      patients treated with intravenous tissue-type plasminogen activator 3 to 4.5
      hours from onset in everyday practice in the United States, there is no evidence
      for increased risk or worse outcomes compared with standard treatment<=3 hours.

PMID- 24092552
TI  - Extradural internal carotid artery caliber dysregulation is associated with
      cerebral aneurysms.
AB  - BACKGROUND AND PURPOSE: Flow-induced hemodynamic forces are critical in extra-
      and intracranial arterial caliber regulation and have been proposed to mediate
      intracranial aneurysm (IA) formation and rupture. We hypothesized that vascular
      structural control may be impaired in patients harboring brain aneurysms and
      sought to examine any differences in extradural internal carotid artery (ICA)
      caliber profiles. METHODS: Ninety-six catheter 2-dimensional angiograms were
      divided into 3 subgroups: (1) ICA leading to IA (n=38), (2) matched contralateral
      ICA (n=25), and (3) ICA from nonaneurysmal controls (n=33). ICA diameter was
      measured proximally beyond the bulb (DProx) and distally at the extradural point
      of maximal dilation (DMaxDist), yielding maximal distal-to-proximal ratio (RMdp).
      RESULTS: Unlike non-IA controls that tapered smoothly, ICAs leading to IA
      consistently demonstrated focal sites of abnormal dilation in the distal cervical
      or petrous extradural segments. RMdp was greater in ICAs leading to IA compared
      with non-IA controls (1.17+/-0.1 versus 1.0+/-0.08; P<0.0001). Matched-pair
      analysis showed RMdp to be higher in ICAs leading to IA than the corresponding
      contralateral ICAs (1.19+/-0.1 versus 1.07+/-0.11; P=0.001); RMdp from
      contralateral ICAs was greater than non-IA controls (P=0.005). Among ICAs leading
      to IA, women showed higher RMdp (1.11+/-0.12 versus 1.05+/-0.11; P=0.02) with no
      relationship to intradural IA location. CONCLUSIONS: Measurements of the
      extradural ICA in patients harboring intradural IA suggest an association with a
      remote upstream abnormal vascular caliber control consistent with a diffuse flow
      mediated structural dysregulation showing laterality and sex dependence.

PMID- 24092553
TI  - Incremental cost effectiveness of pharmacist-managed erythropoiesis-stimulating
      agent clinics for non-dialysis-dependent chronic kidney disease patients.
AB  - BACKGROUND: Pharmacists successfully manage patients with anemia and chronic
      kidney disease (CKD), but the cost effectiveness of these programs is unknown.
      OBJECTIVE: To compare the cost effectiveness of pharmacist-managed erythropoiesis
      stimulating agent (ESA) clinics with that of usual care in patients with non
      dialysis-dependent (NDD)-CKD. METHODS: A Markov model was used to estimate the
      incremental cost effectiveness of pharmacist-managed ESA clinics compared with
      usual care in outpatient veterans receiving ESAs for NDD-CKD in 2009. The
      analysis was conducted from a US Veterans Health Administration perspective with
      a 5-year time horizon, and the year of valuation for cost results was 2012. The
      effect of parameter uncertainty was explored in one-way and probabilistic
      sensitivity analyses. RESULTS: In the deterministic base case analysis, costs and
      effectiveness per patient over 5 years were US$13,412 and 2.096 quality-adjusted
      life-years (QALYs) in the pharmacist-managed ESA clinics and US$16,173 and 2.093
      QALYs in usual care; ESA clinics dominated usual care. In one-way sensitivity
      analyses, ESA clinics no longer dominated if their patients' probability of being
      in the target hemoglobin range fell to 52 % (base case 71 %) or if the mean
      cost/patient/month of epoetin or darbepoetin in ESA clinics increased to
      approximately US$382 (base case US$226) or US$477 (base case US$268),
      respectively. When all parameters were varied simultaneously in a probabilistic
      sensitivity analysis, ESA clinics were favored >=80 % of the time at willingness
      to-pay thresholds of US$0-$100,000 per QALY gained. CONCLUSIONS: Pharmacist
      managed ESA clinics were less costly and more effective than usual care in
      patients receiving ESAs for anemia and NDD-CKD. Results were robust to variation
      and support the use of pharmacist-managed ESA clinics.

PMID- 24092559
TI  - Light polarization-controlled shape-memory polymer/gold nanorod composite.
AB  - It is demonstrated that light polarization can be used to control photothermal
      effect-based shape-memory polymers (SMPs). Gold nanorods (AuNRs) are embedded in
      poly(vinyl alcohol) (PVA) and aligned by stretching the composite film. By
      changing the polarization direction of the incident laser at 785 nm with respect
      to the film stretching direction, the magnitude of the longitudinal surface
      plasmon resonance of AuNRs can be varied continuously, which determines the
      amount of heat generated upon laser exposure and thus the local temperature rise
      in the composite relative to the glass transition of the PVA matrix.
      Consequently, the temporary-to-permanent shape recovery process of the composite
      can be made to occur to different extents by tuning the polarization of laser
      while keeping all other conditions unchanged. This finding enhances the toolbox
      for controlling light-triggered SMPs. 

PMID- 24092554
TI  - 2013 update of the 2011 American College of Rheumatology recommendations for the
      treatment of juvenile idiopathic arthritis: recommendations for the medical
      therapy of children with systemic juvenile idiopathic arthritis and tuberculosis
      screening among children receiving biologic medications.

PMID- 24092562
TI  - Isolated and spontaneous correction of proximal interphalangeal joint
      contractures in Dupuytren's disease: an exploratory analysis of the efficacy and
      safety of collagenase Clostridium histolyticum.
AB  - BACKGROUND AND OBJECTIVE: Dupuytren's contractures affecting proximal
      interphalangeal (PIP) joints are challenging to treat. We explored the effects of
      collagenase Clostridium histolyticum (CCH) on PIP joint contractures after
      injection of an affected metacarpophalangeal (MP) joint in the same finger and
      after injection of an isolated PIP joint contracture. METHODS: Two patient
      subsets were evaluated: those with MP/PIP joints contractures in the same finger,
      but only the MP joint contractures were treated (Group A); and those with
      isolated PIP joint contractures that were treated (Group B). Endpoints included
      correction and improvement in contracture. Fixed-flexion contracture (FFC) and
      range of motion (ROM) were also assessed; adverse events (AEs) were monitored.
      RESULTS: In Group A, 28 and 43 % of PIP contractures spontaneously corrected
      after the first and last injection of CCH, respectively, for MP contractures; 40
      and 63 %, respectively, improved. In Group B, 31 and 39 % of PIP joint
      contractures corrected after the first and last injection of CCH, respectively,
      56 and 66 %, respectively, improved. In Groups A and B, FFC improvements were
      largest after the last injection; ROM improvements were largest after the last
      injection in Group A and third injection in Group B. For 46 and 44 % of patients
      in Groups A and B, respectively, the first injection was the last injection. In
      Group B, the median (minimum, maximum) injections/joint was 1.0 (1.0, 4.0).
      Nearly all patients (98 %) experienced >=1 AE; most were injection-site
      reactions. CONCLUSIONS: The efficacy of CCH for improving PIP joint contracture
      was similar whether treated in isolation or after treatment of an MP joint
      contracture.

PMID- 24092563
TI  - ESR statement on radiation protection: globalisation, personalised medicine and
      safety (the GPS approach).
AB  - In keeping with its responsibility for the radiation protection of patients
      undergoing radiological examinations and procedures, as well as of staff who are
      getting exposed, and with due regard to requirements under European Directives,
      the European Society of Radiology (ESR) issues this statement. It provides a
      holistic approach, termed as Globalisation (indicating all the steps and
      involving all stakeholders), Personalisation (referring to patient-centric) and
      Safety-thus called GPS. MAIN MESSAGES: While being conscious that there is need
      to increase access of radiological imaging, ESR is aware about the increasing
      inappropriate medical exposures to ionising radiation and wide variation in
      patient doses for the same examination. The ESR is convinced that the different
      components of radiation protection are often interrelated and cannot be
      considered in isolation The ESR's GPS approach stands for: Globalisation
      (indicating all the steps and involving all stakeholders), Personalisation
      (referring to patient-centric) and Safety-thus called GPS It can be anticipated
      that enhanced protection of patients in Europe will result through the GPS
      approach. Although the focus is on patient safety, staff safety issues will find
      a place wherever pertinent.

PMID- 24092564
TI  - Contrast-induced nephropathy: pharmacology, pathophysiology and prevention.
AB  - Modern iodinated contrast media (CM) consist of one or two tri-iodobenzene rings.
      They differ from each other in the composition of the side chains, creating
      different molecules and thus different brand substances. After intravascular
      administration, all CM are distributed rapidly into intravascular and
      extracellular fluids. They are eliminated solely by glomerular filtration. In
      patients with normal renal function, CMs are eliminated within 24 h. The
      pathophysiology of contrast-induced nephropathy (CIN) is based on three distinct
      but interacting mechanisms: medullary ischaemia, formation of reactive oxygen
      species and direct tubular cell toxicity. The contribution of each of these
      mechanisms to the development of CIN in the individual patient remains unclear.
      CIN prevention is extensively described in guidelines, such as the recently
      updated guideline from the Contrast Media Safety Committee (CMSC) of the European
      Society of Urogenital Radiology (ESUR). The recent update is briefly discussed.
      Furthermore, it remains unclear if volume expansion with either NaCl 0.9 % or
      NaHCO3 1.4 % is superior. Teaching points * After intravascular injection, CM are
      distributed over intravascular and extracellular fluids. * CM are eliminated by
      glomerular filtration in patients with normal kidney function. * CIN
      pathophysiology is based on medullary ischaemia, formation of reactive oxygen
      species (ROS) and tubular cell toxicity. * It remains unclear if volume expansion
      with either NaCl 0.9 % or NaHCO 3 1.4 % is superior. 

PMID- 24092565
TI  - Temporal relationship between multiple drugs and multiple events in patient
      reports on adverse drug reactions: findings in a pilot study in Japan.

PMID- 24092566
TI  - Increased ectodomain shedding of lung epithelial cell adhesion molecule 1 as a
      cause of increased alveolar cell apoptosis in emphysema.
AB  - RATIONALE: Alveolar epithelial cell apoptosis and protease/antiprotease imbalance
      based proteolysis play central roles in the pathogenesis of pulmonary emphysema
      but molecular mechanisms underlying these two events are not yet clearly
      understood. Cell adhesion molecule 1 (CADM1) is a lung epithelial cell adhesion
      molecule in the immunoglobulin superfamily. It generates two membrane associated
      C terminal fragments (CTFs), alphaCTF and betaCTF, through protease mediated
      ectodomain shedding. OBJECTIVE: To explore the hypothesis that more CADM1-CTFs
      are generated in emphysematous lungs through enhanced ectodomain shedding, and
      cause increased apoptosis of alveolar epithelial cells. METHODS AND RESULTS:
      Western blot analyses revealed that CADM1-CTFs increased in human emphysematous
      lungs in association with increased ectodomain shedding. Increased apoptosis of
      alveolar epithelial cells in emphysematous lungs was confirmed by terminal
      nucleotide nick end labelling (TUNEL) assays. NCI-H441 lung epithelial cells
      expressing mature CADM1 but not CTFs were induced to express alphaCTF both
      endogenously (by shedding inducers phorbol ester and trypsin) and exogenously (by
      transfection). Cell fractionation, immunofluorescence, mitochondrial membrane
      potentiometric JC-1 dye labelling and TUNEL assays revealed that CADM1-alphaCTF
      was localised to mitochondria where it decreased mitochondrial membrane potential
      and increased cell apoptosis. A mutation in the intracytoplasmic domain abrogated
      all three abilities of alphaCTF. CONCLUSIONS: CADM1 ectodomain shedding appeared
      to cause alveolar cell apoptosis in emphysematous lungs by producing alphaCTF
      that accumulated in mitochondria. These data link proteolysis to apoptosis, which
      are two landmark events in emphysema.

PMID- 24092567
TI  - Combination of budesonide/formoterol on demand improves asthma control by
      reducing exercise-induced bronchoconstriction.
AB  - BACKGROUND: In mild asthma exercise-induced bronchoconstriction (EIB) is usually
      treated with inhaled short-acting beta2 agonists (SABAs) on demand. OBJECTIVE:
      The hypothesis was that a combination of budesonide and formoterol on demand
      diminishes EIB equally to regular inhalation of budesonide and is more effective
      than terbutaline inhaled on demand. METHODS: Sixty-six patients with asthma (>12
      years of age) with verified EIB were randomised to terbutaline (0.5 mg) on
      demand, regular budesonide (400 MUg) and terbutaline (0.5 mg) on demand, or a
      combination of budesonide (200 MUg)  + formoterol (6 MUg) on demand in a 6-week,
      double-blind, parallel-group study (ClinicalTrials.gov identifier: NCT00989833).
      The patients were instructed to perform three to four working sessions per week.
      The main outcome was EIB 24 h after the last dosing of study medication. RESULTS:
      After 6 weeks of treatment with regular budesonide or budesonide+formoterol on
      demand the maximum post-exercise forced expiratory volume in 1 s fall, 24 h after
      the last medication, was 6.6% (mean; 95% CI -10.3 to -3.0) and 5.4% (-8.9 to 
      1.8) smaller, respectively. This effect was superior to inhalation of terbutaline
      on demand (+1.5%; -2.1 to +5.1). The total budesonide dose was approximately 2.5
      times lower in the budesonide+formoterol group than in the regular budesonide
      group. The need for extra medication was similar in the three groups.
      CONCLUSIONS: The combination of budesonide and formoterol on demand improves
      asthma control by reducing EIB in the same order of magnitude as regular
      budesonide treatment despite a substantially lower total steroid dose. Both these
      treatments were superior to terbutaline on demand, which did not alter the
      bronchial response to exercise. The results question the recommendation of
      prescribing SABAs as the only treatment for EIB in mild asthma.

PMID- 24092568
TI  - Scopolamine detoxification technique for heroin dependence: a randomized trial.
AB  - BACKGROUND: Easing psychological symptoms associated with heroin use and heroin
      relapse are important goals in the treatment of heroin dependence. However, most
      detoxification methods are designed to decrease withdrawal-related discomfort and
      complications, but not to reduce the psychological effects of heroin addiction.
      OBJECTIVE: The objective of this study was to evaluate the efficacy of
      scopolamine detoxification technique (SDT) relative to standard methadone
      detoxification (MD) to treat heroin withdrawal and psychological symptoms
      associated with heroin use and relapse. METHODS: In this 10-week randomized,
      controlled trial, treatment-seeking heroin-dependent participants were enrolled
      consecutively from Ningbo Addiction Research and Treatment Center, Ningbo, China.
      Opioid dependence was confirmed by a naloxone challenge test. Participants were
      included if they met Diagnostic and Statistical Manual of Mental Disorders,
      fourth edition (DSM-IV) criteria for opioid dependence, were without major
      comorbid psychiatric illness, and were not allergic to scopolamine and
      chlorpromazine. Participants (N = 91; 18-50 years) were admitted to inpatient
      beds for 15 days and randomly assigned to receive either SDT (N = 46) or MD (N =
      45) prior to being discharged and undergoing 8 weeks of outpatient treatment.
      During the inpatient stay, all participants received methadone during days 1-3.
      Those in the MD group then underwent a 10-day gradual dose-reduction regimen.
      Those in the SDT group underwent an SDT, such that subjects were given
      scopolamine (0.03-0.05 mg/kg, intravenously) and chlorpromazine (0.6-1.0 mg/kg,
      intravenously) under light anesthesia for 4-6 h once per day on days 4-6 or 4-7,
      depending on the severity of opioid-withdrawal symptoms. Self-reported withdrawal
      symptoms were assessed each day during the in-patient treatment phase. Heroin
      craving (assessed using a visual analog scale), Beck Depression Inventory, Self
      Rating Anxiety Scale, and working memory and attention tests (assessed using the
      Digit-span test and d2 test) were measured before (day 0) and after
      detoxification (day 15). Retention was assessed during the inpatient phase and
      the outpatient phase. Urine tests for opioids were assessed twice weekly in the
      follow-up phase. Reasons for Relapse Questionnaires were completed when each
      participant's urine sample was positive. RESULTS: The vital signs of participants
      were stable and no serious adverse anesthetic events were observed during SDT.
      SDT considerably suppressed heroin withdrawal symptoms, which did not increase
      during the post-detoxification phase. Although groups did not differ on retention
      or the percentage of opioid-positive urine samples (SDT 73.2 +/- 30.1% and MD
      75.1 +/- 37.6%), SDT significantly attenuated heroin craving, depression, and
      anxiety compared with MD (P < 0.001). There was a significant difference in the
      mean reductions (%) of amount of first heroin use after hospital discharge
      between the SDT group and the MD group (t 71 = 6.09, P < 0.01). There were no
      significant differences in the scores of the Digit-span and d2 tests by treatment
      conditions (P > 0.05). The percentage of participants citing "drug craving" and
      "anxiety and depression" as the primary reasons for relapse was significantly
      lower in the SDT group than in the MD group. CONCLUSIONS: SDT may be an
      alternative to conventional detoxification techniques, especially for patients
      with psychological symptoms.

PMID- 24092569
TI  - Generic products of antiepileptic drugs: a perspective on bioequivalence,
      bioavailability, and formulation switches using Monte Carlo simulations.
AB  - INTRODUCTION: Generic products of antiepileptic drugs (AEDs) are currently a
      controversial topic as neurologists and patients are reluctant to switch from
      brand products to generics and to switch between generics. OBJECTIVE: The aim of
      this study was to provide enlightenment on issues of bioequivalence (BE) and
      interchangeability of AED products. METHODS: Monte Carlo simulations of the
      classic 2 * 2 BE studies were performed to study the effect of sample size,
      within-subject variability, and the true difference in pharmacokinetic values of
      the products under comparison on BE acceptance of generic AED products.
      Simulations were extended to study the comparative performance of two generic AED
      products against the same innovative product. The simulated results are compared
      with literature data on AEDs. RESULTS: The question with regard to
      bioavailability (BA) is whether two formulations are different, while for BE the
      question is whether two formulations are sufficiently similar in terms of extent
      and rate of absorption. Therefore, the criteria for BA and BE and the statistical
      analysis involved in their analysis are different. Two generic formulations that
      meet regulatory approval requirements for generics by being bioequivalent to the
      same innovative AED may not be bioequivalent to one another and therefore should
      not be regarded as equal or as therapeutically equivalent products. A switch from
      a standard or an immediate-release formulation to a modified-release product,
      which comprises extended-release or delayed-release formulations, should not be
      regarded as a switch between generics, but rather as a switch between different
      formulation types. DISCUSSION: Switches between bioequivalent generic AED
      products could potentially lead to larger changes in plasma levels and exposure
      than the brand-to-generic switch. The simulation work verified the clinical
      findings that not all generic AED products bioequivalent to the same innovative
      product are bioequivalent to one another. CONCLUSIONS: Two generic formulations
      that meet regulatory approval requirements for generics, by being bioequivalent
      to the innovative AED, may not be bioequivalent to one another. Additional BE
      criteria are needed for a formulation switch, particularly in epilepsy, where a
      breakthrough seizure may change a patient's status from seizure-free to
      refractory.

PMID- 24092570
TI  - HDAC5 promotes osteosarcoma progression by upregulation of Twist 1 expression.
AB  - Histone deacetylases (HDACs) form a family of enzymes, which have fundamental
      roles in the epigenetic regulation of gene expression and contribute to the
      growth, differentiation, and apoptosis of cancer cells. In this study, we firstly
      investigated the biological function of HDAC5 in osteosarcoma cells. We found
      that mRNA and protein levels of HDAC5 were upregulated in osteosarcoma tissues
      and cell lines. Furthermore, overexpression of HDAC5 could promote cell
      proliferation in osteosarcoma cell lines. In contrast, HDAC5 knockdown using
      small interfering RNA inhibited cell proliferation. At the molecular level, we
      demonstrated that HDAC5 promoted mRNA expression of twist 1, which has been
      reported as an oncogene. Together, these results highlighted for the first time
      an unrecognized link between HDAC5 and osteosarcoma progression and demonstrated
      that its specific inhibition might contribute to the treatment of tumorigenesis. 

PMID- 24092571
TI  - Inhibition of focal adhesion kinase induces apoptosis in human osteosarcoma SAOS
      2 cells.
AB  - Focal adhesion kinase (FAK), a non-receptor tyrosine kinase protein, acts as an
      early modulator of integrin signaling cascade, regulating basic cellular
      functions. In transformed cells, unopposed FAK signaling has been considered to
      promote tumor growth, progression, and metastasis. The aim of this study was to
      assess the role of focal adhesion kinase in human osteosarcoma SAOS-2 cells. SAOS
      2 cells were transfected with PGPU6/GFP/shNC, and PGPU6/GFP/FAK-334 (shRNA-334),
      respectively. Expression of FAK was detected by real-time PCR and western blots.
      MTT assay was used to examine changes in cell proliferation. Cell apoptosis was
      analyzed by flow cytometry. The expression of caspase-3,-7,-9 was measured by
      Western blots. The expression of FAK in SAOS-2 cells significantly decreased in
      shRNA-334 group contrast to the control group (P < 0.01). Cells proliferation was
      inhibited by shRNA-334 and shRNA-334 + cisplatin, and the effects were clearly
      enhanced when cells treated with the anticancer agents. The level of cell
      apoptosis in shRNA-334 and shRNA-334 + cisplatin group was higher than in the
      control group (P < 0.01). The current data support evidence that down-regulation
      of FAK could induce SAOS-2 apoptosis through the caspase-dependent cell death
      pathway. Inhibition of the kinases may be important for therapies designed to
      enhance the apoptosis in osteosarcoma.

PMID- 24092572
TI  - Genetic variation in the TP63 gene is associated with lung cancer risk in the Han
      population.
AB  - Lung cancer is one of the most common malignant tumors that seriously threaten
      human health. Current evidence suggests that heredity contributes to the
      progression of lung cancer. To investigate and validate potential genetic
      associations with the risk of lung cancer, we conducted a case-control study
      including 309 cases and 310 controls from Xi'an City, which is located in
      northwest China, and genotyped six SNPs in five genes, which are related to
      metabolic process. Overall, our results show that the SNP rs10937405 was
      associated with a decreased occurrence of lung cancer (OR = 0.72; 95% CI = 0.56
      0.92; p = 0.009). In the genetic models analysis, we found that genotype "CT" of
      rs10937405 in TP63 was associated with a decreased lung cancer risk (OR = 0.71;
      95% CI, 0.51-0.99; p = 0.031); the genotype "TT" of rs10937405 showed a decreased
      lung cancer risk in the co-dominant model (OR = 0.53; 95% CI, 0.30-0.95; p =
      0.031). The genotype "CT-TT" of rs10937405 also showed a decreased lung cancer
      risk in the dominant model (OR = 0.67; 95% CI, 0.49-0.92; p = 0.014) and the log
      additive model (OR = 0.72; 95% CI, 0.56-0.92; p = 0.0085). The genotype "CC-CT"
      of rs10937405 confers a higher risk of lung cancer for males than females. Our
      results, combined with those from previous studies, suggest that genetic
      variation in TP63 may influence lung cancer susceptibility in the Han population.

PMID- 24092573
TI  - Variability of assay methods for total and free PSA after WHO standardization.
AB  - The variability of total PSA (tPSA) and free PSA (fPSA) results among commercial
      assays has been suggested to be decreased by calibration to World Health
      Organization (WHO) reference materials. To characterize the current situation, it
      is necessary to know its impact in the critical cutoffs used in clinical
      practice. In the present study, we tested 167 samples with tPSA concentrations of
      0 to 20 MUg/L using seven PSA and six fPSA commercial assays, including Access,
      ARCHITECT i2000, ADVIA Centaur XP, IMMULITE 2000, Elecsys, and Lumipulse G1200,
      in which we only measured tPSA. tPSA and fPSA were measured in Access using the
      Hybritech and WHO calibrators. Passing-Bablok analysis was performed for PSA, and
      percentage of fPSA with the Hybritech-calibrated access comparison assay. For
      tPSA, relative differences were more than 10 % at 0.2 MUg/L for ARCHITECT i2000,
      and at a critical concentration of 3, 4, and 10 MUg/L, the relative difference
      was exceeded by ADVIA Centaur XP and WHO-calibrated Access. For percent fPSA, at
      a critical concentration of 10 %, the 10 % relative difference limit was exceeded
      by IMMULITE 2000 assay. At a critical concentration of 20 and 25 %, ADVIA Centaur
      XP, ARCHITECT i2000, and IMMULITE 2000 assays exceeded the 10 % relative
      difference limit. We have shown significant discordances between assays included
      in this study despite advances in standardization conducted in the last years.
      Further harmonization efforts are required in order to obtain a complete clinical
      concordance. 

PMID- 24092574
TI  - High expression of nucleobindin 2 mRNA: an independent prognostic factor for
      overall survival of patients with prostate cancer.
AB  - Nucleobindin 2 (NUCB2) has been demonstrated to play critical roles in
      tumorigenesis and tumor development of breast cancer. The expression change of
      nucleobindin 2 at mRNA level in prostate cancer (PCa) tissues compared with
      adjacent benign prostate tissues was detected by using real-time quantitative
      reverse transcriptase-polymerase chain reaction analysis in our previous study.
      The data suggests that NUCB2 is a cancer-related gene associated with the
      aggressive progression and biochemical recurrence-free survival predictor of PCa
      patients. However, the correlation between the expression of the NUCB2 mRNA and
      the overall survival of patients with PCa was not analyzed. Thus, the association
      of NUCB2 mRNA expression with overall survival of PCa patients was analyzed in
      this study. Kaplan-Meier analysis and Cox proportional hazards regression models
      were used to investigate the correlation between NUCB2 mRNA expression and
      prognosis of PCa patients. The Kaplan-Meier survival analysis showed that the
      high expression of NUCB2 was related to the poor overall survival of patients
      with PCa. Multivariate Cox analysis showed that NUCB2 mRNA was an independent
      prognostic factor for overall survival of patients with PCa. In conclusion, we
      demonstrated that high NUCB2 mRNA expression correlated with poor overall
      survival in patients with PCa. 

PMID- 24092575
TI  - Increased SPHK1 expression is associated with poor prognosis in bladder cancer.
AB  - Upregulation of sphingosine kinase 1 (SPHK1) protein has been reported to be
      associated with a poor prognosis in a variety of malignant tumors. However, the
      role of SPHK1 in bladder cancer (BC) has not been thoroughly elucidated. The
      purpose of this study was to assess SPHK1 expression and to explore its
      contribution to BC. Real-time quantitative reverse transcriptase-polymerase chain
      reaction (qRT-PCR) was conducted to detect SPHK1 mRNA expression in 37 pairs of
      fresh-frozen BC tissues and corresponding noncancerous tissues. Results showed
      that SPHK1 mRNA expression level in BC tissues was significantly higher than that
      in corresponding noncancerous tissues. To investigate the association between
      SPHK1 protein expression and clinicopathological characteristics of BC,
      immunohistochemistry (IHC) was performed in 153 archived paraffin-embedded BC
      samples. Interestingly, high SPHK1 expression was significantly associated with
      histologic grade (P = 0.045) and tumor stage (P < 0.001) of patients with BC. The
      Kaplan-Meier survival curve showed that patients with high SPHK1 expression had
      significantly reduced overall 5-year survival rates (P < 0.001). Multivariate Cox
      regression analysis further suggested that the increased expression of SPHK1 was
      an independent poor prognostic factor for this disease. In conclusion, our data
      offer the convincing evidence for the first time that the increased expression of
      SPHK1 may be involved in the pathogenesis and progression of BC. SPHK1 might be a
      potential marker to predict the prognosis in BC. 

PMID- 24092576
TI  - Pioglitazone prescription increases risk of bladder cancer in patients with type
      2 diabetes: an updated meta-analysis.
AB  - Pioglitazone is widely used for glycemic control in patients with type 2 diabetes
      mellitus, but evidence regarding the association between pioglitazone and bladder
      cancer risk is confusing. A systematic search of databases was carried out, and
      other relevant papers were also identified. Then, the analyses were conducted
      according to the PRISMA and MOOSE guidelines. After quality assessment, nine
      datasets from 10 available studies were included on the basis of inclusion
      criteria. The incidence of bladder cancer among pioglitazone ever users and never
      users, pooled from four cohort and one randomized studies, were 84.51 and 66.68
      per 100,000 person-years, respectively. Nine studies representing 2,596,856
      diabetic patients were recognized as eligible for overall study; the result
      suggested an increased risk of bladder cancer in patients exposed to
      pioglitazone. A persistent significance was detected after being adjusted by age,
      gender, and use of other diabetes medications. Subgroup analyses indicated that
      the significantly increased incidence of bladder cancer was found in men, but not
      in women. Additionally, the analyses addressing increasing exposure to
      pioglitazone observed a dose-response relation between exclusive ever use of
      pioglitazone and bladder cancer in terms of cumulative duration of use and
      cumulative dosage. With some limitations, our results suggest an increased risk
      of bladder cancer in diabetic patients using pioglitazone, especially for men
      with long-term and high-dose exposure. Additional studies are needed to provide
      more precise evidences to support our results. 

PMID- 24092577
TI  - Roles and relationships.

PMID- 24092578
TI  - Broad versus blanket consent for research with human biological samples.

PMID- 24092579
TI  - Demystifying biobanks.

PMID- 24092581
TI  - Back to basics about organ donation.

PMID- 24092580
TI  - The author replies.

PMID- 24092582
TI  - Bedside.

PMID- 24092583
TI  - The unpatentable human being.

PMID- 24092584
TI  - Time to decriminalize HIV status.

PMID- 24092585
TI  - Case study. Googling a patient. Commentary.

PMID- 24092586
TI  - The Presidential Bioethics Commission: pedagogical materials and bioethics
      education.

PMID- 24092587
TI  - Bloomberg's Health Legacy: urban innovator or meddling nanny?

PMID- 24092589
TI  - The next step for quality attestation.

PMID- 24092588
TI  - Quality attestation for clinical ethics consultants: a two-step model from the
      American Society for Bioethics and Humanities.

PMID- 24092590
TI  - Does quality attestation come in only one size?

PMID- 24092591
TI  - The research-clinical practice distinction, learning health systems, and
      relationships.

PMID- 24092593
TI  - Undocumented patients and the not-so-safe safety net.

PMID- 24092594
TI  - The examined life. A tribute to Edmund Pellegrino.

PMID- 24092595
TI  - Impacts of nomad sedentarization on social and ecological systems at multiple
      scales in Xinjiang Uyghur autonomous region, China.
AB  - China's government is now promoting the Nomad Sedentarization Project (NSP) in
      large areas of grassland as a solution for ecological restoration and poverty
      alleviation. To examine the effects of this policy, we conducted in-depth
      interviews at two of the project's sites and examined the social and ecological
      systems at village, county, and catchment scales in Jinghe County of Xinjiang. We
      found that (1) the NSP in one village greatly improved the household standard of
      living and changed their resource utilization modes; (2) the success in this
      village can be attributed to resources imported from the social and ecological
      systems at larger scales, and could not be repeated in a second nearby village
      with different constraints; and (3) the NSP is poorly adapted to local ecosystem
      characteristics, and may therefore have negative impacts at larger scales. To
      avoid these problems, holistic assessments are necessary to judge the NSP's
      impacts on social and ecological systems at multiple scales, and the program must
      be implemented cautiously to account for the potential risks in ecologically
      vulnerable areas. 

PMID- 24092596
TI  - Patient-Reported Outcome Measures in Safety Event Reporting: PROSPER Consortium
      guidance.
AB  - The Patient-Reported Outcomes Safety Event Reporting (PROSPER) Consortium was
      convened to improve safety reporting by better incorporating the perspective of
      the patient. PROSPER comprises industry, regulatory authority, academic, private
      sector and patient representatives who are interested in the area of patient
      reported outcomes of adverse events (PRO-AEs). It has developed guidance on PRO
      AE data, including the benefits of wider use and approaches for data capture and
      analysis. Patient-reported outcomes (PROs) encompass the full range of self
      reporting, rather than only patient reports collected by clinicians using
      validated instruments. In recent years, PROs have become increasingly important
      across the spectrum of healthcare and life sciences. Patient-centred models of
      care are integrating shared decision making and PROs at the point of care;
      comparative effectiveness research seeks to include patients as participatory
      stakeholders; and industry is expanding its involvement with patients and patient
      groups as part of the drug development process and safety monitoring.
      Additionally, recent pharmacovigilance legislation from regulatory authorities in
      the EU and the USA calls for the inclusion of patient-reported information in
      benefit-risk assessment of pharmaceutical products. For patients, technological
      advancements have made it easier to be an active participant in one's healthcare.
      Simplified internet search capabilities, electronic and personal health records,
      digital mobile devices, and PRO-enabled patient online communities are just a few
      examples of tools that allow patients to gain increased knowledge about
      conditions, symptoms, treatment options and side effects. Despite these changes
      and increased attention on the perceived value of PROs, their full potential has
      yet to be realised in pharmacovigilance. Current safety reporting and risk
      assessment processes remain heavily dependent on healthcare professionals, though
      there are known limitations such as under-reporting and discordant perspectives
      between patient reports and clinician perceptions of adverse outcomes. PROSPER
      seeks to support the wider use of PRO-AEs. The scope of this guidance document,
      which was completed between July 2011 and March 2013, considered a host of
      domains related to PRO-AEs, including definitions and suitable taxonomies, the
      range of datasets that could be used, data collection mechanisms, and suitable
      analytical methodologies. PROSPER offers an innovative framework to differentiate
      patient populations. This framework considers populations that are prespecified
      (such as those in clinical trials, prospective observational studies and some
      registries) and non-prespecified populations (such as those in claims databases,
      PRO-enabled online patient networks, and social websites in general). While the
      main focus of this guidance is on post-approval PRO-AEs from both prespecified
      and non-prespecified population groups, PROSPER has also considered pre-approval,
      prespecified populations. The ultimate aim of this guidance is to ensure that the
      patient 'voice' and perspective feed appropriately into collection of safety
      data. The guidance also covers a minimum core dataset for use by industry or
      regulators to structure PRO-AEs (accessible in the online appendix) and how data,
      once collected, might be evaluated to better inform on the safe and effective use
      of medicinal products. Structured collection of such patient data can be
      considered both a means to an end (improving patient safety) as well as an end in
      itself (expressing the patient viewpoint). The members of the PROSPER Consortium
      therefore direct this PRO-AE guidance to multiple stakeholders in drug safety,
      including industry, regulators, prescribers and patients. The use of this
      document across the entirety of the drug development life cycle will help to
      better define the benefit-risk profile of new and existing medicines. Because of
      the clinical relevance of 'real-world' data, PROs have the potential to
      contribute important new knowledge about the benefits and risks of medicinal
      products, communicated through the voice of the patient. 

PMID- 24092597
TI  - ATLANTIC DIP: simplifying the follow-up of women with previous gestational
      diabetes.
AB  - OBJECTIVE: Previous gestational diabetes (GDM) is associated with a significant
      lifetime risk of type 2 diabetes. In this study, we assessed the performance of
      HbA1c and fasting plasma glucose (FPG) measurements against that of 75 g oral
      glucose tolerance testing (OGTT) for the follow-up screening of women with
      previous GDM. METHODS: Two hundred and sixty-six women with previous GDM
      underwent the follow-up testing (mean of 2.6 years (s.d. 1.0) post-index
      pregnancy) using HbA1c (100%), and 75 g OGTT (89%) or FPG (11%). American
      Diabetes Association (ADA) criteria for abnormal glucose tolerance were used.
      DESIGN, COHORT STUDY, AND RESULTS: The ADA HbA1c high-risk cut-off of 39 mmol/mol
      yielded sensitivity of 45% (95% CI 32, 59), specificity of 84% (95% CI 78, 88),
      negative predictive value (NPV) of 87% (95% CI 82, 91) and positive predictive
      value (PPV) of 39% (95% CI 27, 52) for detecting abnormal glucose tolerance. ADA
      high-risk criterion for FPG of 5.6 mmol/l showed sensitivity of 80% (95% CI 66,
      89), specificity of 100% (95% CI 98, 100), NPV of 96% (95% CI 92, 98) and PPV of
      100% (95% CI 91, 100). Combining HbA1c >=39 mmol/mol with FPG >=5.6 mmol/l
      yielded sensitivity of 90% (95% CI 78, 96), specificity of 84% (95% CI 78, 88),
      NPV of 97% (95% CI 94, 99) and PPV of 56% (95% CI 45, 66). CONCLUSIONS: Combining
      test cut-offs of 5.6 mmol/l and HbA1c 39 mmol/mol identifies 90% of women with
      abnormal glucose tolerance post-GDM (mean 2.6 years (s.d.1.0) post-index
      pregnancy). Applying this follow-up strategy will reduce the number of OGTT tests
      required by 70%, will be more convenient for women and their practitioners, and
      is likely to lead to increased uptake of long-term retesting by these women whose
      risk for type 2 diabetes is substantially increased.

PMID- 24092598
TI  - Video game therapy for emotional regulation and impulsivity control in a series
      of treated cases with bulimia nervosa.
AB  - Although standard psychological treatments have been successful in treating
      several core features in eating disorders (ED), other characteristics such as
      emotional regulation or impulsivity appear to be more resistant to change. There
      is a growing body of evidence to support the efficacy of cognitive remediation
      for cognitive and emotional difficulties in ED. Playmancer/ Islands is a video
      game (VG) designed to specifically treat mental disorders, characterized by
      problems in impulse control. The objective of the game is to increase self
      control over emotions, decision making and behaviours. The aim of this study is
      to describe the results from a consecutive series of nine bulimia nervosa
      patients who were treated with the VG in addition to cognitive behaviour therapy
      (CBT). The outcomes included clinical and psychopathological questionnaires, and
      physiological measures were obtained during the VG. Emotional regulation
      improved, heart rate variability increased, and respiratory rate and impulsivity
      measures reduced after the treatment. These findings suggest that VG training may
      enhance treatment for ED.

PMID- 24092599
TI  - Adult smokers' receptivity to a television advert for electronic nicotine
      delivery systems.
AB  - OBJECTIVE: The aim of the present work was to examine adult smokers' awareness of
      and receptivity to an electronic nicotine delivery system (ENDS) television
      advert, and whether viewing the advert influenced urge to smoke and intention to
      try ENDS. METHODS: A television advert for ENDS brand blu eCigs was shown to an
      online convenience sample of 519 Florida adult smokers. We measured current
      smokers' awareness of and receptivity to the advert, and whether seeing the
      advert influenced their thoughts about smoking or quitting, urge to smoke and
      intention to try ENDS. Results were stratified by prior ENDS use. RESULTS:
      Approximately 62.3% of current smokers were aware of the advert. Smokers found
      the advert informative (73.8%), attention grabbing (67.5%) and innovative
      (64.5%), with prior ENDS users rating the advert more favourably than non-users.
      Seeing the advert elicited an urge to smoke (mean 42.1, SD=1.9) and thoughts
      about smoking cigarettes (75.8%) as well as quitting (74.6%). Prior END users
      were significantly more likely than non-users to report thinking about smoking
      cigarettes after seeing the advert (P<0.05). Most smokers said ENDS were 'made
      for people like them' (88.6%) and they would try ENDS in the future (66.0%).
      CONCLUSIONS: Smokers are receptive to ENDS television adverts and report
      intention to try ENDS after viewing the advert. Future studies should monitor
      ENDS advertising and examine how exposure to ENDS adverts influences smokers' use
      of ENDS, dual use with cigarettes and cessation behaviour.

PMID- 24092600
TI  - Trends in the use of premium and discount cigarette brands: findings from the ITC
      US Surveys (2002-2011).
AB  - OBJECTIVE: The purpose of this paper was to examine trends in the use of premium
      and discount cigarette brands and determine correlates of type of brand used and
      brand switching. METHODS: Data from the International Tobacco Control (ITC) US
      adult smoker cohort survey were analysed. The total study sample included 6669
      adult cigarette smokers recruited and followed from 2002 to 2011 over eight
      different survey waves. Each survey wave included an average of 1700 smokers per
      survey with replenishment of those lost to follow-up. RESULTS: Over the eight
      survey waves, a total of 260 different cigarette brands were reported by smokers,
      of which 17% were classified as premium and 83% as discount brands. Marlboro,
      Newport, and Camel were the most popular premium brands reported by smokers in
      our sample over all eight survey waves. The percentage of smokers using discount
      brands increased between 2002 and 2011, with a marked increase in brand switching
      from premium to discount cigarettes observed after 2009 corresponding to the
      $0.61 increase in the federal excise tax on cigarettes. Cigarette brand
      preferences varied by age group and income levels with younger, higher income
      smokers more likely to report smoking premium brand cigarettes, while older,
      middle and lower income, heavier smokers were more likely to report using
      discount brands. CONCLUSIONS: Our data suggest that demographic and smoking
      trends favour the continued growth of low priced cigarette brands. From a tobacco
      control perspective, the findings from this study suggest that governments should
      consider enacting stronger minimum pricing laws in order to keep the base price
      of cigarettes high, since aggressive price marketing will likely continue to be
      used by manufacturers to compete for the shrinking pool of remaining smokers in
      the population.

PMID- 24092603
TI  - Four-year follow-up of megalencephaly, polymicrogyria, postaxial polydactyly and
      hydrocephalus (MPPH) syndrome.
AB  - A male infant was born by emergent caesarean section at 39 weeks gestational age
      secondary to maternal and fetal distress. Initial physical examination was
      notable for macrocephaly (greater than+2SD), postaxial polydactyly of the hands
      and facial dysmorphism. Head imaging demonstrated diffuse polymicrogyria without
      hydrocephalus. All findings were consistent with a diagnosis of megalencephaly,
      polymicrogyria, postaxial polydactyly and hydrocephalus (MPPH) syndrome. At the 4
      year follow-up, megalencephaly persisted without evidence of hydrocephalus. The
      child was severely delayed with a stable seizure disorder controlled with dual
      antiepileptic therapy. This case meets the classic criteria for MPPH syndrome,
      adding to the limited experience with this disease. The 4-year follow-up and
      absence of hydrocephalus, once thought to be a key diagnostic criterion, adds to
      our understanding of the long-term sequelae. 

PMID- 24092604
TI  - Extensive acute disseminated encephalomyelitis in a young girl responding to
      intravenous methylprednisolone.
AB  - Acute disseminated encephalomyelitis (ADEM) is a monophasic clinical syndrome,
      characterised by immune-mediated demyelination of the central nervous system.
      Differentiating ADEM from acute viral encephalomyelitis may pose a difficult
      clinical challenge. We describe a 3-year-old girl who presented with fever,
      weakness in all four limbs, urinary retention, respiratory distress and altered
      sensorium. MRI of the brain showed multiple cerebral T2-hyperintense signals with
      bilateral thalamic and basal ganglia involvement. MRI of the spine showed
      extensive T2-hyperintensities from cervical to lumbar spinal cord. Cerebrospinal
      fluid examination was normal. The patient was diagnosed as ADEM and treated with
      intravenous methylprednisolone. She showed complete clinical and radiological
      improvement at the end of 1-month follow-up. 

PMID- 24092605
TI  - Peripancreatic cystic lymphangioma diagnosed by endoscopic ultrasound/fine-needle
      aspiration: a rare mesenchymal tumour.
AB  - A 73-year-old man presented with a 5-month history of intermittent nausea,
      vomiting, central abdominal discomfort and a 17-pound weight loss over the past
      year. Laboratory testing, including a complete blood count with differential,
      liver function testing, amylase and lipase studies were normal. A CT scan showed
      a bilobed cystic lesion inferior to the body of the pancreas. An endoscopic
      ultrasound revealed a 5.3*3.9 cm, anechoic, bilobed cystic lesion, extrinsic to
      the body of the pancreas with a 1-2 mm septation and a normal pancreas. Fine
      needle aspiration revealed a milky-white aspirate with negative cytology.
      Laboratory assessment of the cystic aspirant revealed carcinoembryonic antigen
      1.7 ng/mL, amylase 148 units/L, cholesterol 300 mg/dL, and carbohydrate antigen
      19-9 3 units/mL. He underwent resection of the mass, with the histopathology
      confirming a diagnosis of peripancreatic lymphangioma. He did well after the
      surgery with interval resolution of his symptoms. 

PMID- 24092606
TI  - Disassociation at the head-trunnion interface: an unseen complication of modular
      hip hemiarthroplasty.
AB  - A woman in her mid-90s underwent a left uncemented bipolar hemiarthroplasty for
      an intracapsular femoral neck fracture. Postoperative radiographs at 48h showed a
      disassociation of the left femoral prosthesis at the head-trunnion interface,
      with the bipolar head remaining in the acetabulum. There was no preceding trauma
      and the patient had mobilised postoperatively. The hip was revised to a monopolar
      head, and the patient's hip was protected postoperatively in a brace limiting
      flexion and external rotation. At 30 days following revision she was mobilising
      pain-free with a stable hip. Disassociation at the head-trunnion interface has
      never been reported in hip hemiarthroplasty, and is only described in relation to
      primary or revision total hip replacements (THR) following dislocation or trauma
      to the THR. This demonstrates a potential complication of modular prostheses for
      trauma. 

PMID- 24092607
TI  - Single coronary artery: anomalous origin of right coronary artery from the left
      anterior descending artery.

PMID- 24092608
TI  - Vesicovaginal fistula due to vaginal herb for primary infertility: could it be
      devastating?
AB  - Vesicovaginal fistula (VVF) is a very commonly encountered urogynaecological
      entity in developing countries such as India. The most common cause of VVF in
      developing counties is secondary to obstructive labour. We report a very unusual
      case of VVF in a young woman that developed due to insertion of an unknown
      vaginal herb for treatment of primary infertility. Cystoscopy showed a single
      trigonal fistula measuring 3*2 cm just near the bladder neck. Vaginoscopy
      revealed cicatrised less capacious vagina and unhealthy vaginal mucosa. She was
      treated with transvaginal VVF repair using Martius flap interposition which
      leaked on 10th postoperative day. She underwent re-evaluation and another
      transvaginal fistula repair for small trigonal residual fistula after 3 months.
      She is doing well during the follow-up of 2 years. She attained sexual activity
      after 3 months of surgical repair but could not conceive. 

PMID- 24092609
TI  - Quinine-induced severe thrombocytopenia: the importance of taking a detailed drug
      history.
AB  - Drugs can lead to severe life-threatening thrombocytopenia. The mechanisms of
      drug-induced thrombocytopenia are increased destruction by immune-mediated
      platelet destruction or decreased platelet production by bone marrow suppression.
      Quinine is a drug used for the treatment of malaria and nocturnal leg cramps and
      is also an important ingredient in some herbal preparations. Quinine can very
      rarely cause thrombocytopenia by immune-mediated platelet destruction. In a
      patient with thrombocytopenia, a detailed history of all the medications
      including over-the-counter medications and herbal preparations is very important.

PMID- 24092610
TI  - Strangulated diaphragmatic hernia presenting at 7 weeks of life as intractable
      shock.
AB  - A 7-week-old infant presented to hospital pale and floppy, with 5 s capillary
      refill time. Blood gas showed severe acidosis (pH 6.86, partial pressure of
      carbondioxide 10.55 kPa, base excess 21.1). Hypotension persisted despite several
      fluid boluses so she was intubated and started on inotropic support. A chest X
      ray revealed a congenital diaphragmatic hernia (CDH). Despite steroids and blood
      transfusions she remained unstable, and could not be resuscitated following
      cardiac arrest. Postmortem revealed 39 cm of herniated, necrotic colon. 5-25% of
      CDH presents after the neonatal period, and while not associated with pulmonary
      hypoplasia is primarily still a diaphragmatic defect. In late presenting cases,
      herniation occurs shortly prior to developing symptoms; therefore, an antenatal
      ultrasound (US) cannot pick it up. If we could diagnose the isolated
      diaphragmatic defect antenatally, this would allow elective postnatal surgical
      closure. This is not feasible currently; however, with the advent of antenatal
      three-dimensional US scans it may be possible in the future. 

PMID- 24092611
TI  - Cardiac arrest: first presentation of anorexia nervosa.
AB  - A 16-year-old girl collapsed in cardiac arrest in a hospital car park.
      Investigations revealed a potassium level of 1.8. Following a 5-day intensive
      care unit admission she described behaviours consistent with restrictive-purging
      type anorexia nervosa, which had been concealed from her parents and health
      professionals. Long-term management has been difficult due to poor patient
      engagement. Further, recurrent episodes of hypokalaemia continue to feature. Here
      we explore the cardiac complications of anorexia nervosa and challenges with long
      term management of this condition. 

PMID- 24092612
TI  - Imaging features in Takotsubo cardiomyopathy.

PMID- 24092613
TI  - Targeting hyperglycaemia with anti-obesity drugs: time for a paradigm shift?

PMID- 24092614
TI  - Epigenetics and psychiatry.
AB  - Psychiatric disorders including major depressive disorder, drug addiction, and
      schizophrenia are debilitating illnesses with a multitude of complex symptoms
      underlying each of these disorders. In recent years, it has become appreciated
      that the onset and development of these disorders goes beyond the one gene-one
      disease approach. Rather, the involvement of many genes is likely linked to these
      illnesses, and regulating the activation or silencing of gene function may play a
      crucial role in contributing to their pathophysiology. Epigenetic modifications
      such as histone acetylation and deacetylation, as well as DNA methylation can
      induce lasting and stable changes in gene expression, and have therefore been
      implicated in promoting the adaptive behavioral and neuronal changes that
      accompany each of these illnesses. In this review we will discuss some of the
      latest work implicating a potential role for epigenetics in psychiatric
      disorders, namely, depression, addiction, and schizophrenia as well as a possible
      role in treatment. 

PMID- 24092616
TI  - Looking above but not beyond the genome for therapeutics in neurology and
      psychiatry: epigenetic proteins and RNAs find a new focus.

PMID- 24092615
TI  - The epigenetics of stroke recovery and rehabilitation: from polycomb to histone
      deacetylases.
AB  - Classical de-afferentation studies, as well as experience-dependent visual
      plasticity paradigms, have confirmed that both the developing and adult nervous
      system are capable of unexpected levels of plasticity. This capacity is
      underscored by the significant spontaneous recovery that can occur in patients
      with mild-to-moderate impairment following stroke. An evolving model is that an
      interaction of biological and environmental factors during all epochs post-stroke
      influences the extent and quality of this plasticity. Here, we discuss data that
      have implicated specific epigenetic proteins as integrators of environmental
      influences in 3 aspects of stroke recovery: spontaneous impairment reduction in
      humans; peri-infarct rewiring in animals as a paradigm for developing
      therapeutically-driven impairment reduction beyond natural spontaneous recovery;
      and, finally, classical hippocampal learning and memory paradigms that are
      theoretically important in skill acquisition for both impairment reduction and
      compensatory strategies in the rehabilitation setting. Our discussion focuses
      primarily on B lymphoma Mo-MLV1 insertion region proteins of the polycomb
      repressive complex, alpha thalassemia/mental retardation syndrome X-linked
      chromatin remodeling factors, and the best known and most dynamic gene
      repressors, histone deacetylases. We will highlight exciting current data
      associated with these proteins and provide promising speculation about how they
      can be manipulated by drugs, biologics, or noninvasive stimulation for stroke
      recovery. 

PMID- 24092617
TI  - Effect of silibinin on the pharmacokinetics of nitrendipine in rabbits.
AB  - Silibinin, a major constituent of silymarin, is widely used for its
      hepatoprotective effects. This study investigated the effect of silibinin on the
      pharmacokinetics of oral nitrendipine in rabbits. In first set of experiment,
      male New Zealand rabbits were pretreated with silibinin (50 mg/kg, PO) for 7 days
      and on last day nitrendipine (10 mg/kg, PO) was administered. In second set, both
      silibinin and nitrendipine were coadministered to examine acute effect of
      silibinin on nitrendipine pharmacokinetics. The plasma concentration of
      nitrendipine was estimated by high performance liquid chromatography and
      different pharmacokinetic parameters were calculated using WinNonlin((r))
      software. Coadministration of silibinin had no significant effect on
      pharmacokinetics of nitrendipine when compared to control group. However, a 1.89
      1.57-fold increase in area under the concentration-time curve and peak plasma
      concentration (C max), respectively, of nitrendipine was observed in silibinin
      pretreated group. The mean C max was 0.034 +/- 0.005 MUg/mL (nitrendipine alone)
      and 0.054 +/- 0.006 MUg/mL (nitrendipine after pretreatment with silibinin). The
      time to reach C max, elimination rate constant and elimination half-life of
      nitrendipine were not significantly different among control and silibinin treated
      groups. This study demonstrates that silibinin increase plasma concentration of
      nitrendipine. Henceforth, the pharmacodynamic influence of this interaction
      should be taken into consideration while prescribing nitrendipine to the patients
      already taking silymarin. 

PMID- 24092618
TI  - Comment on: "Clinical management of seizures in newborns: diagnosis and
      treatment".

PMID- 24092619
TI  - Authors' reply to Eugenio Grillo: clinical management of seizures in newborns:
      diagnosis and management.

PMID- 24092620
TI  - Aripiprazole for the treatment and prevention of acute manic and mixed episodes
      in bipolar I disorder in children and adolescents: a NICE single technology
      appraisal.
AB  - As part of its single technology process, the National Institute for Health and
      Care Excellence (NICE) invited the manufacturers of aripiprazole (Otsuka
      Pharmaceutical Co. and Bristol Myers Squibb) to submit evidence of the clinical
      and cost effectiveness of aripiprazole for the treatment and prevention of acute
      manic and mixed episodes in bipolar I disorder in children and adolescents. The
      School of Health and Related Research Technology Appraisal Group at the
      University of Sheffield was commissioned to act as the independent Evidence
      Review Group (ERG). The ERG produced a critical review of the evidence for the
      clinical and cost effectiveness of the technology, based upon the manufacturers'
      submission to NICE. The evidence, which was derived mainly from a double-blind,
      phase III, placebo-controlled trial of aripiprazole in patients aged 10-17 years,
      showed that aripiprazole performed significantly better than placebo in reducing
      mania according to the primary outcome measurement (the Young Mania Rating Scale
      at 4 weeks). Safety outcomes indicated that aripiprazole was significantly more
      likely to cause extrapyramidal symptoms and somnolence than placebo. The
      manufacturers also presented a network meta-analysis of aripiprazole versus other
      atypical antipsychotics commonly used to treat manic episodes (olanzapine,
      quetiapine and risperidone) to show that aripiprazole performed similarly to the
      comparator drugs in terms of efficacy and safety. Aripiprazole was demonstrated
      to perform better in safety outcomes of (1) less weight gain than olanzapine and
      quetiapine; and (2) less prolactin increase than olanzapine, quetiapine and
      risperidone. Results from the manufacturers' economic evaluation showed that use
      of aripiprazole second-line dominated all of the other treatment strategies that
      were considered. However, there was considerable uncertainty in this result, and
      clinical advisors indicated that the actual treatment strategy employed in
      practice is likely to be dependent upon the patient's characteristics. The ERG
      demonstrated that if this personalised medicine resulted in improved cost
      effectiveness for any of the other treatment strategies, then they had the
      potential to dominate use of aripiprazole second-line. In conclusion, whilst a
      strategy including aripiprazole appeared to be cost effective relative to a
      strategy without it, there was not robust enough evidence to recommend a specific
      place for aripiprazole within the treatment pathway.

PMID- 24092621
TI  - Metabolomics.

PMID- 24092627
TI  - The impact of a community-based clinical trial educational intervention among
      underrepresented Chinese Americans.
AB  - BACKGROUND: Clinical trials are a critical resource for the discovery of new
      prevention, diagnostic, and treatment methods for cancer. The most effective
      prevention and treatment modalities are based on previous clinical trial results.
      However, participation in clinical trials is underrepresented by racial/ethnic
      minority populations, Asian Americans in particular. Asian Americans are the
      least represented of any ethnic groups in clinical trials. The purpose of this
      study is to develop and evaluate a culturally and linguistically appropriate
      community-based educational intervention to increase knowledge of and intent to
      participate in cancer clinical trials among underrepresented Chinese Americans.
      METHODS: Community-Based Participatory Research approach was used to guide the
      development, cultural tailoring, implementation, and evaluation of clinical trial
      intervention. First, 22 Asian community representatives were recruited as
      community health educators (CHE) who received 12-hour training on clinical trial
      education. Second, 262 members were recruited from 11 Chinese community
      organizations. Of those recruited, a total of 247 eligible Chinese enrolled and
      participated in the clinical trial education delivered by trained CHEs.
      Participants completed pretest before and posttest after the intervention.
      RESULTS: Fifteen of 21 measures of clinical trial knowledge showed significant
      changes post the intervention (P < 0.05). Education remained the sole demographic
      factor increasing clinical trial knowledge in multivariate analysis. CONCLUSION:
      Clinical trial education should emphasize both benefits to science and the larger
      Asian community. This community-based clinical trial intervention demonstrated
      promising results and has potential to enhance recruitment and participation in
      clinical trial research among the underrepresented Asian Americans. IMPACT:
      Improving clinical trial participation in the fast-growing Asian American
      population is key to dissemination of health innovations targeted to diminish
      health disparities.

PMID- 24092629
TI  - Fluorescence imaging for visualization of the ion cloud in a quadrupole ion trap
      mass spectrometer.
AB  - Laser-induced fluorescence is used to visualize populations of gaseous ions
      stored in a quadrupole ion trap (QIT) mass spectrometer. Presented images include
      the first fluorescence image of molecular ions collected under conditions
      typically used in mass spectrometry experiments. Under these "normal" mass
      spectrometry conditions, the radial (r) and axial (z) full-width at half maxima
      (FWHM) of the detected ion cloud are 615 and 214 MUm, respectively, corresponding
      to ~6% of r0 and ~3% of z0 for the QIT used. The effects on the shape and size of
      the ion cloud caused by varying the pressure of helium bath gas, the number of
      trapped ions, and the Mathieu parameter q z are visualized and discussed. When a
      "tickle voltage" is applied to the exit end-cap electrode, as is done in
      collisionally activated dissociation, a significant elongation in the axial, but
      not the radial, dimension of the ion cloud is apparent. Finally, using
      spectroscopically distinguishable fluorophores of two different m/z values,
      images are presented that illustrate stratification of the ion cloud; ions of
      lower m/z (higher qz) are located in the center of the trapping region,
      effectively excluding higher m/z (lower qz) ions, which form a surrounding layer.
      Fluorescence images such as those presented here provide a useful reference for
      better understanding the collective behavior of ions in radio frequency (rf)
      trapping devices and how phenomena such as collisions and space-charge affect ion
      distribution.

PMID- 24092628
TI  - N-acetyltransferase 2 phenotype, occupation, and bladder cancer risk: results
      from the EPIC cohort.
AB  - BACKGROUND: An association between N-acetyltransferase 2 (NAT2) slow acetylation
      and bladder cancer has been consistently observed in epidemiologic studies.
      However, evidence has been mainly derived from case-control studies and was
      sparse from cohort studies. We evaluated the association between NAT2 slow
      acetylation and bladder cancer in a case-control study nested in the European
      Prospective Investigation into Cancer and Nutrition. METHODS: Exposure to
      aromatic amines and polycyclic aromatic hydrocarbons (PAH) could be assessed for
      754 cases and 833 controls for whom occupational information was documented. A
      semiquantitative job-exposure matrix was applied to at-risk occupations to
      estimate the exposure as low, medium, or high based on tertiles of the
      distribution of the exposure score in controls. Using a comprehensive genotyping,
      NAT2 acetylation status could be categorized from 6-single-nucleotide
      polymorphism genotypes as slow or fast in 607 cases and 695 controls with DNA
      from archived blood samples. RESULTS: Occupational exposure to aromatic amines
      and PAH was associated with an increased bladder cancer risk [upper tertile of
      the distribution of the exposure score: OR = 1.37; 95% confidence interval (CI),
      1.02-1.84, and OR = 1.50; 95% CI, 1.09-2.05, respectively]. NAT2 slow acetylation
      did not modify these risk estimates and was not itself associated with bladder
      cancer risk (OR = 1.02; 95% CI, 0.81-1.29). CONCLUSIONS: These findings confirm
      established or suspected occupational risk factors but not the anticipated role
      of NAT2 slow acetylation in bladder cancer. No interaction was detected between
      NAT2 and any exposure of interest, including smoking. IMPACT: Genetic testing for
      NAT2 would be inappropriate in occupational settings.

PMID- 24092630
TI  - Imaging of noncovalent complexes by MALDI-MS.
AB  - Noncovalent interactions govern how molecules communicate. Mass spectrometry is
      an important and versatile tool for the analysis of noncovalent complexes (NCX).
      Electrospray mass spectrometry (ESI-MS) is the most widely used MS technique for
      the study of NCXs because of its softer ionization and easy compatibility with
      the solution phase of NCX mixtures. Matrix-assisted laser desorption/ionization
      mass spectrometry (MALDI-MS) has also been used to study NCXs. However,
      successful analysis depends upon several experimental factors, such as matrix
      selection, solution pH, and instrumental parameters. In this study, we employ
      MALDI imaging mass spectrometry to investigate the location and formation of
      NCXs, involving both peptides and proteins, in a MALDI sample spot. 

PMID- 24092632
TI  - Investigative trends in understanding penalty-kick performance in association
      football: an ecological dynamics perspective.
AB  - There have been different approaches to studying penalty-kick performance in
      association football and in this paper we synthesize key findings within an
      ecological dynamics theoretical framework. According to this theoretical
      perspective, information is the cornerstone for understanding the dynamics of
      action regulation in penalty-kick performance. Research suggests that
      investigators need to identify the information sources that are most relevant to
      penalty-kick performance. An important task is to understand how constraints can
      channel (i.e. change, emphasize or mask) information sources used to regulate
      upcoming actions and how the influence of these constraints is expressed in
      players' behavioural dynamics. Due to the broad range of constraints influencing
      penalty-kick performance, it is recommended that future research adopts an
      interdisciplinary focus on performance assessment to overcome the current lack of
      representativeness in penalty-kick experimental designs. Such an approach would
      serve to capture the information-based control of action of both players as
      components of this dyadic system in competitive sport. 

PMID- 24092633
TI  - Potential cardiovascular system-protective effects of flavan-3-ol.

PMID- 24092637
TI  - Glucagon-like peptide-1 (GLP-1) reduces mortality and improves lung function in a
      model of experimental obstructive lung disease in female mice.
AB  - The incretin hormone glucagon-like peptide-1 (GLP-1) is an important insulin
      secretagogue and GLP-1 analogs are used for the treatment of type 2 diabetes. GLP
      1 displays antiinflammatory and surfactant-releasing effects. Thus, we
      hypothesize that treatment with GLP-1 analogs will improve pulmonary function in
      a mouse model of obstructive lung disease. Female mice were sensitized with
      injected ovalbumin and treated with GLP-1 receptor (GLP-1R) agonists.
      Exacerbation was induced with inhalations of ovalbumin and lipopolysaccharide.
      Lung function was evaluated with a measurement of enhanced pause in a whole-body
      plethysmograph. mRNA levels of GLP-1R, surfactants (SFTPs), and a number of
      inflammatory markers were measured. GLP-1R was highly expressed in lung tissue.
      Mice treated with GLP-1R agonists had a noticeably better clinical appearance
      than the control group. Enhanced pause increased dramatically at day 17 in all
      control mice, but the increase was significantly less in the groups of GLP-1R
      agonist-treated mice (P < .001). Survival proportions were significantly
      increased in GLP-1R agonist-treated mice (P < .01). SFTPB and SFTPA were down
      regulated and the expression of inflammatory cytokines were increased in mice
      with obstructive lung disease, but levels were largely unaffected by GLP-1R
      agonist treatment. These results show that GLP-1R agonists have potential
      therapeutic potential in the treatment of obstructive pulmonary diseases, such as
      chronic obstructive pulmonary disease, by decreasing the severity of acute
      exacerbations. The mechanism of action does not seem to be the modulation of
      inflammation and SFTP expression. 

PMID- 24092638
TI  - Development of a methodology for and assessment of pulsatile luteinizing hormone
      secretion in juvenile and adult male mice.
AB  - Current methodology to monitor pulsatile LH release in mice is limited by
      inadequate assay sensitivity, resulting in the need for collection of large blood
      volumes. Thus, assessment of pulsatile LH secretion in mice remains highly
      challenging, and observations are limited to adult mice. To address this, we
      developed a highly sensitive ELISA for assessment of mouse LH concentrations in
      small fractions of whole blood. We demonstrate that this assay is capable of
      reliably detecting LH down to a theoretical limit of 0.117 ng/mL in a 2-MUL
      fraction of whole blood. Using an established frequent blood collection
      procedure, we validated the accuracy of this method by determining the pulsatile
      LH secretion in early-adult (10 weeks old) C57BL6/J male mice. Data demonstrate
      regular pulsatile release of LH, with peaks in LH secretion rarely exceeding 3
      ng/mL. Moreover, assessment of LH release in Gpr54 knockout mice demonstrates the
      lack of pulsatile LH release after the loss of kisspeptin-mediated pubertal
      maturation. We next determined age-associated changes in pulsatile LH secretion
      by assessment of LH secretion in prepubertal (28 days old) C57BL6/J male mice and
      repeated assessment in the same mice in adulthood (120 days old). Data
      demonstrate that the rise in total LH secretion in mice after pubertal maturation
      occurs along with an overall rise in the pulsatile LH secretion rate. This was
      coupled with a significant increase in the number of LH secretory events (number
      of pulses). In addition, we observed a decrease in the clearance (increased half
      life) and a decrease in the regularity (approximate entropy) of LH release. This
      method will be of wide general utility within the field of reproductive biology. 

PMID- 24092631
TI  - Bone quality: the determinants of bone strength and fragility.
AB  - Bone fragility is a major health concern, as the increased risk of bone fractures
      has devastating outcomes in terms of mortality, decreased autonomy, and
      healthcare costs. Efforts made to address this problem have considerably
      increased our knowledge about the mechanisms that regulate bone formation and
      resorption. In particular, we now have a much better understanding of the
      cellular events that are triggered when bones are mechanically stimulated and how
      these events can lead to improvements in bone mass. Despite these findings at the
      molecular level, most exercise intervention studies reveal either no effects or
      only minor benefits of exercise programs in improving bone mineral density (BMD)
      in osteoporotic patients. Nevertheless, and despite that BMD is the gold standard
      for diagnosing osteoporosis, this measure is only able to provide insights
      regarding the quantity of bone tissue. In this article, we review the complex
      structure of bone tissue and highlight the concept that its mechanical strength
      stems from the interaction of several different features. We revisited the
      available data showing that bone mineralization degree, hydroxyapatite crystal
      size and heterogeneity, collagen properties, osteocyte density, trabecular and
      cortical microarchitecture, as well as whole bone geometry, are determinants of
      bone strength and that each one of these properties may independently contribute
      to the increased or decreased risk of fracture, even without meaningful changes
      in aBMD. Based on these findings, we emphasize that while osteoporosis (almost)
      always causes bone fragility, bone fragility is not always caused just by
      osteoporosis, as other important variables also play a major role in this
      etiology. Furthermore, the results of several studies showing compelling data
      that physical exercise has the potential to improve bone quality and to decrease
      fracture risk by influencing each one of these determinants are also reviewed.
      These findings have meaningful clinical repercussions as they emphasize the fact
      that, even without leading to improvements in BMD, exercise interventions in
      patients with osteoporosis may be beneficial by improving other determinants of
      bone strength. 

PMID- 24092639
TI  - The acid-secreting parietal cell as an endocrine source of Sonic Hedgehog during
      gastric repair.
AB  - Sonic Hedgehog (Shh) has been shown to regulate wound healing in various tissues.
      Despite its known function in tissue regeneration, the role of Shh secreted from
      the gastric epithelium during tissue repair in the stomach remains unknown. Here
      we tested the hypothesis that Shh secreted from the acid-secreting parietal cell
      is a fundamental circulating factor that drives gastric repair. A mouse model
      expressing a parietal cell-specific deletion of Shh (PC-ShhKO) was generated
      using animals bearing loxP sites flanking exon 2 of the Shh gene (Shh(flx/flx))
      and mice expressing a Cre transgene under the control of the H(+),K(+)-ATPase
      beta-subunit promoter. Shh(flx/flx), the H(+),K(+)-ATPase beta-subunit promoter,
      and C57BL/6 mice served as controls. Ulcers were induced via acetic acid injury.
      At 1, 2, 3, 4, 5, and 7 days after the ulcer induction, gastric tissue and blood
      samples were collected. Parabiosis experiments were used to establish the effect
      of circulating Shh on ulcer repair. Control mice exhibited an increased
      expression of Shh in the gastric tissue and plasma that correlated with the
      repair of injury within 7 days after surgery. PC-ShhKO mice showed a loss of
      ulcer repair and reduced Shh tissue and plasma concentrations. In a parabiosis
      experiment whereby a control mouse was paired with a PC-ShhKO littermate and both
      animals subjected to gastric injury, a significant increase in the circulating
      Shh was measured in both parabionts. Elevated circulating Shh concentrations
      correlated with the repair of gastric ulcers in the PC-ShhKO parabionts.
      Therefore, the acid-secreting parietal cell within the stomach acts as an
      endocrine source of Shh during repair. 

PMID- 24092640
TI  - Endothelial metabolism of angiotensin II to angiotensin III, not angiotensin (1
      7), augments the vasorelaxation response in adrenal cortical arteries.
AB  - Hyperaldosteronism is linked to the development and progression of several
      different cardiovascular diseases. Angiotensin (Ang) II increases aldosterone
      secretion and adrenal blood flow. Ang II peptide fragments are produced by
      various peptidases, and these Angs have diverse and vital physiologic roles. Due
      to the uncharacteristic vasorelaxation of adrenal arteries by Ang II, we tested
      the hypothesis that Ang II metabolism contributes to its relaxant activity in
      adrenal arteries. Metabolism of Angs by bovine adrenal cortical arteries and
      isolated bovine adrenal vascular cells was measured by liquid chromatography-mass
      spectrometry. The primary Ang metabolites of adrenal arteries are Ang III and Ang
      (1-7), with Ang IV produced to a lesser extent. Bovine microvascular endothelial
      cells produced a similar metabolic profile to adrenal arteries, whereas bovine
      adrenal artery smooth muscle cells exhibited less metabolism. In preconstricted
      adrenal arteries, Ang II caused relaxation in picomolar concentrations and
      constrictions at 10nM. Ang-converting enzyme 2 inhibition augmented this
      relaxation response, whereas aminopeptidase inhibition did not. Ang III was
      equipotent to Ang II in relaxing adrenal arteries. Ang IV did not cause
      relaxation. Nitric oxide synthase inhibition enhanced Ang II-induced constriction
      of adrenal arteries. Aminopeptidase inhibition increased the concentration range
      for Ang II-induced constriction of adrenal arteries. Ang III and Ang IV did not
      change the basal tone but caused constriction of adrenal arteries with nitric
      oxide synthase inhibition. These data indicate that Ang II metabolism modulates
      the vascular effects of Ang II in the adrenal vasculature. 

PMID- 24092641
TI  - Thyroid autoantibodies are rare in nonhuman great apes and hypothyroidism cannot
      be attributed to thyroid autoimmunity.
AB  - The great apes include, in addition to Homo, the genera Pongo (orangutans),
      Gorilla (gorillas), and Pan, the latter comprising two species, P. troglodytes
      (chimpanzees) and P. paniscus (bonobos). Adult-onset hypothyroidism was
      previously reported in 4 individual nonhuman great apes. However, there is scarce
      information on normal serum thyroid hormone levels and virtually no data for
      thyroid autoantibodies in these animals. Therefore, we examined thyroid hormone
      levels and TSH in all nonhuman great ape genera including adults, adolescents,
      and infants. Because hypothyroidism in humans is commonly the end result of
      thyroid autoimmunity, we also tested healthy and hypothyroid nonhuman great apes
      for antibodies to thyroglobulin (Tg), thyroid peroxidase (TPO), and the TSH
      receptor (TSHR). We established a thyroid hormone and TSH database in orangutans,
      gorillas, chimpanzees, and bonobos (447 individuals). The most striking
      differences are the greatly reduced free-T4 and free-T3 levels in orangutans and
      gorillas vs chimpanzees and bonobos, and conversely, elevated TSH levels in
      gorillas vs Pan species. Antibodies to Tg and TPO were detected in only 2.6% of
      adult animals vs approximately 10% in humans. No animals with Tg, TPO, or TSHR
      antibodies exhibited thyroid dysfunction. Conversely, hypothyroid nonhuman great
      apes lacked thyroid autoantibodies. Moreover, thyroid histology in necropsy
      tissues was similar in euthyroid and hypothyroid individuals, and lymphocytic
      infiltration was absent in 2 hypothyroid animals. In conclusion, free T4 and free
      T3 are lower in orangutans and gorillas vs chimpanzees and bonobos, the closest
      living human relatives. Moreover, thyroid autoantibodies are rare and
      hypothyroidism is unrelated to thyroid autoimmunity in nonhuman great apes. 

PMID- 24092642
TI  - He who is well prepared has half won the battle: an FMRI study of task
      preparation.
AB  - The neural mechanism underlying preparation for tasks that vary in difficulty has
      not been explored. This functional magnetic resonance imaging study manipulated
      task difficulty by varying the working memory (WM) load of the n-back task. Each
      n-back task block was preceded by a preparation period involving a screen that
      indicated the level of difficulty of the upcoming task. Consistent with previous
      work, activation in some brain regions depended on WM load in the task. These
      regions were used as regions of interest for the univariate and multivariate
      (classification) analyses of preparation periods. The findings were that the
      patterns of brain activation during task preparation contain information about
      the upcoming task difficulty. (1) A support vector machine classifier was able to
      decode the n-back task difficulty from the patterns of brain activation during
      task preparation. Those individuals whose activation patterns for anticipated 1-
      versus 2- versus 3-back conditions were classified with higher accuracy showed
      better behavioral performance on the task, suggesting that task performance
      depends on task preparation. (2) Left inferior frontal gyrus, intraparietal
      sulcus, and anterior cingulate cortex parametrically decreased activation as
      anticipated task difficulty increased. Taken together, these results suggest
      dynamic involvement of the WM network not only during WM task performance, but
      also during task preparation. 

PMID- 24092643
TI  - 2013 Colorado alphaherpesvirus latency symposium.

PMID- 24092646
TI  - Is there a role for MDR1, EPHX1 and protein Z gene variants in modulation of
      warfarin dosage? a study on a cohort of the Egyptian population.
AB  - BACKGROUND: There is considerable inter-individual variability in warfarin
      dosages necessary to achieve target therapeutic anticoagulation. Polymorphisms in
      genes, which master warfarin pharmacokinetics and pharmacodynamics, might
      influence warfarin dose variation. Genes encoding drug transporters, such as
      human multidrug resistance (MDR1), as well as epoxide hydrolase 1 (EPHX1), which
      is a putative subunit of the vitamin K epoxide reductase, and Protein Z (PZ),
      which is a vitamin K-dependent plasma glycoprotein, are among those candidate
      genes. OBJECTIVE: The purpose of this study was to investigate the contribution
      of MDR1 C3435T, EPHX1 H139R and PZ A-13G gene polymorphisms in warfarin dose
      variation in a cohort of the Egyptian population. METHODS: Eighty-four patients
      whose international normalized ratio (INR) was in the range of 2-3, 41 males and
      43 females, with a mean (+/-SD) age of 40.9 (13.3) years were recruited into this
      study. MDR1 C3435T, EPHX1 H139R and PZ A-13G gene polymorphisms were detected by
      polymerase chain reaction-restriction fragment length polymorphism. Primarily,
      linear regression analysis, including the variables age, gender, MDR1 C3435T,
      EPHX1 H139R and combined MDR1 C3435T, EPHX1 H139R and PZ A-13G genotypes, was
      used to assess the effective factors for warfarin maintenance dose. Secondly, the
      previously examined cytochrome P450 (CYP) 2C9 A1075C and vitamin K epoxide
      reductase complex subunit 1 (VKORC1) C1173T were added to the regression
      analysis. RESULTS: Warfarin dose/week was not influenced by each of the MDR1
      C3435T, EPHX1 H139R, and PZ A-13G gene polymorphisms when examined separately.
      However, when these single nucleotide polymorphisms (SNPs) were combined, MDR1
      TT/EPHX1 RH,RR/PZ AA subjects showed statistically significant increase in
      warfarin dose/week when compared with MDR1 CC/EPHX1 RH,RR/PZ AA subjects [median
      (25th-75th percentiles): 49.0 (42.0-59.5) vs. 35.0 (24.5-42.0) mg/week,
      respectively] (p = 0.014). In contrast, in the presence of wild-type EPHX1 HH,
      there was a decrease in warfarin dose/week in MDR1 TT subjects when compared with
      CT and CC subjects [median (25th-75th percentiles): 22.0 (17.5-30.6), 42.0 (35.0
      49.0) and 42.0 (28.0-54.3) mg/week, respectively] (p = 0.005 and 0.030,
      respectively). Age had a significant contribution (p = 0.048) to the overall
      variability in warfarin dose. Calculated weekly dose = 52.928 - (0.289 * age) +
      (9.709 * combined genotype). The multivariate linear regression equation of
      warfarin maintenance dose accounted for about 8 % of variation in dose (R (2) =
      0.079), age accounted for 5 % of variation, while combined genotypes added the
      extra 3 %. However, the new regression equation accounted for 20.9 % of variation
      in dose. Age accounted for 5 %, while VKORC1 C1173T accounted for an extra 13 %
      of variation and MDR1 C3435T accounted for the remaining 3 % of variation.
      Calculated dose = 64.909 - (0.282 * age) - (13.390 * VKORC1) - (7.164 * MDR1).
      Correlation analysis showed a close and significant relationship between the
      calculated and actual warfarin dose (r = 0.457; p < 0.0005). CONCLUSION: Warfarin
      dose/week was significantly influenced by the combined MDR1 C3435T and EPHX1
      H139R gene polymorphism since no polymorphism of PZ A-13G SNP was detected in our
      studied Egyptian population. Future studies with larger sample size will be
      needed to confirm our findings before definitive conclusions can be made.

PMID- 24092647
TI  - Aortic wall stress in hypertension and ascending thoracic aortic aneurysms:
      implications for antihypertensive therapy.
AB  - The objective of this study was the evaluation of aortic wall stress in patients
      with ascending thoracic aortic aneurysms (TAA) because of the paucity of data to
      guide medical therapy for blood pressure (BP) management in TAA. Twelve men, age
      67.4 +/- 3.3 years (SEM) with hypertension and ascending TAA without other
      etiology, previous aortic surgery or associated significant aortic valve disease,
      had maximum dimensions of the ascending aorta measured from CT angiogram (CTa)
      and transthoracic echocardiogram (TTE) with aortic wall thickness measured on
      TTE. Wall stress (WS(sigma)(P)) at peak systolic BP (SBP) was expressed by the
      equation: WS(sigma)(P) = 2LCSA * SBP/MCSA, where LCSA is ascending aorta luminal
      cross-sectional area; MCSA is the surface area of the aortic wall cross sectional
      area considering aortic wall thickness. There was no significant difference in
      wall stress from TTE or CTa although mean wall stress was slightly larger when
      calculated from CTa. For each 5 mmHg increment in Systolic BP (SBP), there was a
      3.9 kPa increase in wall stress that was 3.5 kPa for small aneurysms (40 to <45
      mm) and 4.4 kPa for larger aneurysms (45-52 mm). There was a 33.0 +/- 1.2 %
      reduction in wall stress when SBP went from 165 to 110 mmHg with a 21.0 +/- 0.7 %
      reduction in wall stress found when SBP was reduced from 140 to 110 mmHg. These
      data, in patients with hypertension and ascending TAA suggest that meaningful
      reductions in aortic wall stress occur with reductions of SBP and this benefit
      extends to SBP levels <140 mmHg. 

PMID- 24092649
TI  - Environmental microbial proteomics: new avenues for a molecular understanding of
      the functional role of microorganisms in the natural environment.

PMID- 24092653
TI  - Be a good listener and be persistent.

PMID- 24092648
TI  - Antihypertensive treatment and renal protection: the role of drugs inhibiting the
      renin-angiotensin-aldosterone system.
AB  - The prevalence of chronic kidney disease, currently estimated to vary between 8
      and 12 % in the general population, is steadily rising due to aging and to the
      ongoing epidemic of hypertension and type 2 diabetes. Even in its early stages,
      chronic kidney disease entails a greater risk for cardiovascular mortality, and
      its prevention and treatment is rapidly becoming a key medical issue for many
      health care systems worldwide. Adequate blood pressure control and reduction of
      urine protein excretion, preferably obtained by the use of renin-angiotensin
      aldosterone system inhibitors, have traditionally been considered the mainstay of
      therapeutic strategies in patients with renal disease. Given the pivotal role of
      renin-angiotensin-aldosterone system activity in the pathogenesis and progression
      of renal and cardiovascular damage, a more profound inhibition of the system,
      either by the use of multiple agents or by a single agent at high dosage has
      recently been advocated, especially in the presence of proteinuria. Recent
      trials, however have failed to confirm the usefulness of this therapeutic
      approach, at least in unselected patients. This article will critically review
      the current literature and will discuss the clinical implications of targeting
      the renin-angiotensin-aldosterone system in order to provide the greatest renal
      protection. 

PMID- 24092654
TI  - A founder SDHB mutation in Portuguese paraganglioma patients.

PMID- 24092655
TI  - Effect of subinhibitory concentrations of four commonly used biocides on the
      conjugative transfer of Tn916 in Bacillus subtilis.
AB  - OBJECTIVES: Large amounts of biocides are used to reduce and control bacterial
      growth in the healthcare sector, food production and agriculture. This work
      explores the effect of subinhibitory concentrations of four commonly used
      biocides (ethanol, hydrogen peroxide, chlorhexidine digluconate and sodium
      hypochlorite) on the conjugative transposition of the mobile genetic element
      Tn916. METHODS: Conjugation assays were carried out between Bacillus subtilis
      strains. The donor containing Tn916 was pre-exposed to subinhibitory
      concentrations of each biocide for a defined length of time, which was determined
      by an analysis of the transcriptional response of the promoter upstream of tet(M)
      using beta-glucuronidase reporter assays. RESULTS: Ethanol significantly (P =
      0.01) increased the transfer of Tn916 by 5-fold, whereas hydrogen peroxide,
      chlorhexidine digluconate and sodium hypochlorite did not significantly affect
      the transfer frequency. CONCLUSIONS: These results suggest that exposure to
      subinhibitory concentrations of ethanol may induce the transfer of Tn916-like
      elements and any resistance genes they contain.

PMID- 24092656
TI  - Occurrence of multiple chloroquine-resistant Pfcrt haplotypes and emergence of
      the S(agt)VMNT type in Cameroonian Plasmodium falciparum.
AB  - OBJECTIVES: The main objective of this study was to unravel the distribution of
      different Pfcrt genotypes in the central, littoral, eastern and southern regions
      of Cameroon and also in locations bordering Gabon and Equatorial Guinea. This is
      because (i) the chloroquine-resistant malaria parasite Plasmodium falciparum
      shows a wide occurrence in Cameroon, (ii) mutations in the 72nd to 76th amino
      acid positions of the Pfcrt gene are known to confer resistance to chloroquine,
      and (iii) only a single chloroquine-resistant haplotype (C72V73I74E75T76) has so
      far been reported in Cameroon. METHODS: We followed a molecular approach with DNA
      sequencing of the second exon of the Pfcrt gene to identify single nucleotide
      polymorphisms in 180 P. falciparum field isolates sampled in five different
      locations in Cameroon. RESULTS: The chloroquine-resistant Pfcrt CVIET haplotype
      was most abundant, followed by the wild-type CVMNK haplotype. Five hitherto
      unreported chloroquine-resistant Pfcrt haplotypes were detected for the first
      time in Cameroonian P. falciparum, including the surprise appearance of the
      S(agt)VMNT haplotype. CONCLUSIONS: The high observed haplotype diversity of the
      chloroquine-resistant Pfcrt gene and the appearance of the S(agt)VMNT haplotype
      are daunting and can be attributed to drug pressure and/or the misuse of
      chloroquine and/or amodiaquine in Cameroon.

PMID- 24092657
TI  - Carbapenemase-producing Enterobacteriaceae and non-Enterobacteriaceae from
      animals and the environment: an emerging public health risk of our own making?
AB  - Acquired carbapenemases pose one of the most pressing public health threats
      relating to antibiotic resistance. In most countries, the number of carbapenemase
      producing bacteria from human clinical specimens is rising, and the
      epidemiological status of these multiresistant bacteria is progressively
      worsening. Furthermore, there is a growing number of reports of carbapenemases
      found either in bacteria isolated from non-human sources or in Salmonella
      enterica subsp. enterica, a zoonotic species. However, carbapenemases are not yet
      systematically sought in bacteria from non-human sources, reports of them are
      largely observational, and there is limited investigation of carbapenemase
      positive bacteria in animals and possible links with people who may have acted as
      potential sources. Active surveillance and monitoring for carbapenem-resistant
      bacteria in the food chain and other non-human sources is urgently needed, with
      an enhanced and rigorous follow-up of all positive results. The carbapenems are
      currently our last good defence against multiresistant Gram-negative bacteria.
      Our ability to limit the rise and spread of carbapenemase producers, which occur
      only at basal levels in many countries at present, should serve as a key
      performance indicator for the success or failure of the efforts that have been
      called for by international organizations and governments to reduce the impact of
      antibiotic resistance. 

PMID- 24092658
TI  - Reduced susceptibility to vancomycin in isogenic Staphylococcus aureus strains of
      sequence type 59: tracking evolution and identifying mutations by whole-genome
      sequencing.
AB  - OBJECTIVES: Vancomycin-intermediate Staphylococcus aureus (VISA) and
      heterogeneous VISA (hVISA) phenotypes are increasingly reported in methicillin
      resistant S. aureus (MRSA) strains of distinct genetic backgrounds. This study
      tracked genetic evolution during the development of vancomycin non-susceptibility
      in a prevalent Asian community-associated MRSA clone of sequence type (ST) 59.
      METHODS: ST59 strains were consecutively isolated from a patient who failed
      chemotherapy for a septic knee over 15 months. The genetic mutations associated
      with the VISA phenotype were identified by whole-genome sequencing of two
      strains, which had the vancomycin-susceptible S. aureus (VSSA) and VISA
      phenotypes. The mutations were subsequently screened in other strains. By
      correlating the accumulated mutations with vancomycin susceptibility, genetic
      evolution was tracked at the whole-genome scale. RESULTS: Nine non-synonymous
      mutations and two steps of genetic evolution were identified during the
      development of the VISA phenotype. The first step involved a nonsense mutation in
      agrC and point mutations at five other loci, which were associated with the VSSA
      to-hVISA conversion. Mutations of rpoB and fusA following the use of rifampicin
      and fusidic acid were identified in the second step of evolution, which
      corresponded to the development of dual resistance to rifampicin and fusidic acid
      and the conversion of hVISA to VISA. CONCLUSIONS: In vivo genetic evolution of S.
      aureus occurred in stepwise order during the development of incremental
      vancomycin non-susceptibility and was related to the use of antimicrobial agents.

PMID- 24092659
TI  - Outbreak in a haematology unit involving an unusual strain of glycopeptide
      resistant Enterococcus faecium carrying both vanA and vanB genes.
AB  - OBJECTIVES: To report an outbreak due to an unusual strain of Enterococcus
      faecium containing both the vanA and vanB genes, in France, where the rate of
      glycopeptide-resistant enterococci (GRE) is below 1%. METHODS: Cases were
      patients infected or colonized with GRE on the haematology ward. Contact patients
      were screened by real-time PCR performed on rectal swabs. Clinical features were
      compared for GRE-positive and GRE-negative patients. GRE isolates were
      characterized by phenotypic and molecular methods including PFGE. Conjugation
      experiments were performed to identify van genetic support. RESULTS: After the
      index patient presented a bacteraemia with vanA/vanB E. faecium, 56 contact
      patients were screened, 7 of whom were found to be GRE positive: 6 additional
      cases with vanA/vanB E. faecium and 1 with GRE carrying vanA only. PFGE confirmed
      the clonal relationship of the seven vanA/vanB E. faecium strains, whereas the
      vanA isolate was distinct. Only the vanA gene could be transferred to
      enterococcal recipients by conjugation, and it was probably localized on a mobile
      genetic element. All isolates were resistant to vancomycin (MIC > 256 mg/L) and
      teicoplanin (MIC = 24-32 mg/L), but were susceptible to tigecycline (MIC = 0.09
      mg/L), linezolid (MIC = 0.75 mg/L) and daptomycin (MIC = 1-2 mg/L). Significant
      differences (P < 0.001) between carriers and non-carriers of GRE were observed
      for the median duration of hospitalization (57 days versus 16.5 days) and of
      neutropenia (40 days versus 6 days), the median number of antibiotics used (5
      versus 1.5) and the duration of glycopeptide treatment (14.5 days versus 0 days).
      CONCLUSIONS: vanA/vanB E. faecium strains, although rare, can emerge in the
      absence of previous outbreaks of vanA-GRE or vanB-GRE.

PMID- 24092660
TI  - Biliary pharmacodynamic exposure to linezolid in two liver transplant patients.

PMID- 24092661
TI  - Therapeutic drug monitoring of telaprevir in chronic hepatitis C patients
      receiving telaprevir-based triple therapy is useful for predicting virological
      response.
AB  - OBJECTIVES: This prospective, pharmacokinetic study was done to investigate the
      impact of telaprevir plasma trough concentration (Ctrough) in the early stage of
      treatment on the response to telaprevir-based triple therapy for chronic
      hepatitis C patients. METHODS: Participants were 70 chronic hepatitis C patients
      infected with genotype 1. All patients received 12 week triple therapy that
      included telaprevir (2250 mg/day), pegylated interferon-alpha2b (pegylated
      IFNalpha2b) (60-150 MUg/week) and ribavirin (600-1000 mg/day) followed by a 12
      week dual therapy that included pegylated-IFNalpha2b and ribavirin. Plasma
      telaprevir Ctrough was determined by a validated assay using HPLC at days 3, 7
      and 14. The study was registered as a clinical trial on the University Hospital
      Medical Information Network (ID 000009656). RESULTS: The rates of undetectable
      hepatitis C virus RNA at week 4 [rapid virological response (RVR)] and at 24
      weeks after therapy [sustained virological response (SVR)] were 71.4% and 82.9%,
      respectively. Of the patients with RVR, 90% achieved SVR. The mean telaprevir
      Ctrough levels at days 3, 7 and 14 of SVR patients (2.748, 2.733 and 2.999
      MUg/mL, respectively) were significantly higher than those of non-SVR patients
      (1.616, 1.788 and 2.314 MUg/mL, respectively) (all P < 0.05). Multiple logistic
      regression analysis of possible predictors of SVR extracted higher telaprevir
      Ctrough at day 3 (OR 1.012 by 0.001 MUg/mL, P < 0.0001) and interleukin 28B
      (rs8099917) TT allele (OR 6.16 versus non-TT alleles, P < 0.0001). CONCLUSIONS:
      Therapeutic drug monitoring of telaprevir in the early stage of treatment is
      useful in clinical practice for predicting the virological response of patients
      receiving telaprevir-based triple therapy.

PMID- 24092662
TI  - Durability of glycemic control with insulin lispro mix 75/25 versus insulin
      glargine for older patients with type 2 diabetes.
AB  - BACKGROUND AND AIMS: Few studies have evaluated long-term durability of glycemic
      control in older patients. The aim of this study was to compare durability of
      glycemic control of twice-daily insulin lispro mix 75/25 (LM75/25; 75 % insulin
      lispro protamine suspension, 25 % insulin lispro) and once-daily insulin glargine
      (GL) added to oral antihyperglycemic medications in older patients (>=65 years of
      age). METHODS: Patients were participants in the maintenance phase of the DURABLE
      trial. During the initiation phase, patients with type 2 diabetes were randomized
      to LM75/25 or GL. After 6 months, patients with hemoglobin A1c (HbA1c) <=7.0 %
      advanced to the 24-month maintenance phase. The primary objective was between
      group comparison of duration of maintaining the HbA1c goal in older patients
      (>=65 years of age). A similar analysis was conducted for older patients
      achieving HbA1c <=6.5 % in the initiation phase. RESULTS: Median time of
      maintaining HbA1c goal was longer in LM75/25 versus GL (19.6 versus 15.4 months,
      p = 0.007) and more LM75/25 patients maintained goal versus GL (49.2 versus 30.4
      %; p = 0.003). HbA1c reduction from baseline was greater in LM75/25 versus GL (
      1.56 +/- 0.10 versus -1.24 +/- 0.11 %; p = 0.003). Post-meal glucose was
      significantly lower in LM75/25 versus GL (158.86 +/- 3.42 versus 171.67 +/- 4.51
      mg/dL; p = 0.017). No differences were observed in overall and severe
      hypoglycemia. LM75/25 patients had higher daily insulin doses (0.41 +/- 0.02
      versus 0.32 +/- 0.02 units/kg/day; p < 0.001) and more weight gain (5.47 +/- 0.49
      versus 3.10 +/- 0.53 kg; p = 0.001). Similar results were generally obtained in
      older patients with HbA1c <=6.5 %. CONCLUSIONS: In our evaluation of older
      patients from a larger trial, LM75/25 appeared to provide longer durability of
      glycemic control, as well as a greater number of patients maintaining HbA1c goal
      versus GL.

PMID- 24092666
TI  - Successful percutaneous repositioning of a dislodged pacemaker lead.

PMID- 24092663
TI  - The fragile X protein binds mRNAs involved in cancer progression and modulates
      metastasis formation.
AB  - The role of the fragile X mental retardation protein (FMRP) is well established
      in brain, where its absence leads to the fragile X syndrome (FXS). FMRP is almost
      ubiquitously expressed, suggesting that, in addition to its effects in brain, it
      may have fundamental roles in other organs. There is evidence that FMRP
      expression can be linked to cancer. FMR1 mRNA, encoding FMRP, is overexpressed in
      hepatocellular carcinoma cells. A decreased risk of cancer has been reported in
      patients with FXS while a patient-case with FXS showed an unusual decrease of
      tumour brain invasiveness. However, a role for FMRP in regulating cancer biology,
      if any, remains unknown. We show here that FMRP and FMR1 mRNA levels correlate
      with prognostic indicators of aggressive breast cancer, lung metastases
      probability and triple negative breast cancer (TNBC). We establish that FMRP
      overexpression in murine breast primary tumours enhances lung metastasis while
      its reduction has the opposite effect regulating cell spreading and invasion.
      FMRP binds mRNAs involved in epithelial mesenchymal transition (EMT) and invasion
      including E-cadherin and Vimentin mRNAs, hallmarks of EMT and cancer progression.

PMID- 24092664
TI  - Synergistic combination of valproic acid and oncolytic parvovirus H-1PV as a
      potential therapy against cervical and pancreatic carcinomas.
AB  - The rat parvovirus H-1PV has oncolytic and tumour-suppressive properties
      potentially exploitable in cancer therapy. This possibility is being explored and
      results are encouraging, but it is necessary to improve the oncotoxicity of the
      virus. Here we show that this can be achieved by co-treating cancer cells with H
      1PV and histone deacetylase inhibitors (HDACIs) such as valproic acid (VPA). We
      demonstrate that these agents act synergistically to kill a range of human
      cervical carcinoma and pancreatic carcinoma cell lines by inducing oxidative
      stress, DNA damage and apoptosis. Strikingly, in rat and mouse xenograft models,
      H-1PV/VPA co-treatment strongly inhibits tumour growth promoting complete tumour
      remission in all co-treated animals. At the molecular level, we found acetylation
      of the parvovirus nonstructural protein NS1 at residues K85 and K257 to modulate
      NS1-mediated transcription and cytotoxicity, both of which are enhanced by VPA
      treatment. These results warrant clinical evaluation of H-1PV/VPA co-treatment
      against cervical and pancreatic ductal carcinomas. 

PMID- 24092669
TI  - Editorial: from plant biotechnology to bio-based products.
AB  - From plant biotechnology to bio-based products - this Special Issue of
      Biotechnology Journal is dedicated to plant biotechnology and is edited by Prof.
      Eva Stoger (University of Natural Resources and Life Sciences, Vienna, Austria).
      The Special Issue covers a wide range of topics in plant biotechnology, including
      metabolic engineering of biosynthesis pathways in plants; taking advantage of the
      scalability of the plant system for the production of innovative materials; as
      well as the regulatory challenges and society acceptance of plant biotechnology. 

PMID- 24092672
TI  - The use of rice seeds to produce human pharmaceuticals for oral therapy.
AB  - Rice (Oryza sativa L.) is the major staple food consumed by half of the world's
      population. Rice seeds have gained recent attention as bioreactors for the
      production of human pharmaceuticals such as therapeutic proteins or peptides.
      Rice seed production platforms have many advantages over animal cell or microbe
      systems in terms of cost-effectiveness, scalability, safety, product stability
      and productivity. Rice seed-based human pharmaceuticals are expected to become
      innovative therapies as edible drugs. Therapeutic proteins can be sequestered
      within natural cellular compartments in rice seeds and protected from harsh
      gastrointestinal environments. This review presents the state-of-the-art on the
      construction of gene cassettes for accumulation of pharmaceutical proteins or
      peptides in rice seeds, the generation of transgenic rice plants, and challenges
      involved in the use of rice seeds to produce human pharmaceuticals. 

PMID- 24092673
TI  - Natural products - modifying metabolite pathways in plants.
AB  - The diversity of plant natural product (PNP) molecular structures is reflected in
      the variety of biochemical and genetic pathways that lead to their formation and
      accumulation. Plant secondary metabolites are important commodities, and include
      fragrances, colorants, and medicines. Increasing the extractable amount of PNP
      through plant breeding, or more recently by means of metabolic engineering, is a
      priority. The prerequisite for any attempt at metabolic engineering is a detailed
      knowledge of the underlying biosynthetic and regulatory pathways in plants. Over
      the past few decades, an enormous body of information about the biochemistry and
      genetics of biosynthetic pathways involved in PNPs production has been generated.
      In this review, we focus on the three large classes of plant secondary
      metabolites: terpenoids (or isoprenoids), phenylpropanoids, and alkaloids. All
      three provide excellent examples of the tremendous efforts undertaken to boost
      our understanding of biosynthetic pathways, resulting in the first successes in
      plant metabolic engineering. We further consider what essential information is
      still missing, and how future research directions could help achieve the rational
      design of plants as chemical factories for high-value products. 

PMID- 24092674
TI  - Jatropha curcas, a biofuel crop: functional genomics for understanding metabolic
      pathways and genetic improvement.
AB  - Jatropha curcas is currently attracting much attention as an oilseed crop for
      biofuel, as Jatropha can grow under climate and soil conditions that are
      unsuitable for food production. However, little is known about Jatropha, and
      there are a number of challenges to be overcome. In fact, Jatropha has not really
      been domesticated; most of the Jatropha accessions are toxic, which renders the
      seedcake unsuitable for use as animal feed. The seeds of Jatropha contain high
      levels of polyunsaturated fatty acids, which negatively impact the biofuel
      quality. Fruiting of Jatropha is fairly continuous, thus increasing costs of
      harvesting. Therefore, before starting any improvement program using conventional
      or molecular breeding techniques, understanding gene function and the genome
      scale of Jatropha are prerequisites. This review presents currently available and
      relevant information on the latest technologies (genomics, transcriptomics,
      proteomics and metabolomics) to decipher important metabolic pathways within
      Jatropha, such as oil and toxin synthesis. Further, it discusses future
      directions for biotechnological approaches in Jatropha breeding and improvement. 

PMID- 24092675
TI  - Spider silks from plants - a challenge to create native-sized spidroins.
AB  - Silk threads from spiders exhibit extraordinary mechanical properties, such as
      superior toughness and elasticity. Spider silks consist of several different
      large repetitive proteins that act as the basic materials responsible for these
      outstanding features. The production of spider silk protein variants in plants
      opens up new horizons in the production and functional investigation that enable
      the use of spider silks in innovative material development, nanotechnology and
      biomedicine in the future. This review summarizes and discusses production of
      spider silk protein variants in plants, especially with regards to plant
      expression systems, purification strategies, and characteristics of spider silk
      variants. Furthermore, the challenge of producing native-sized recombinant
      spidroins in planta is outlined, presenting three different strategies for
      achieving these high repetitive proteins with the help of non-repetitive C
      terminal domains, crosslinking transglutaminase, and self-linking inteins. The
      potential of these fascinating proteins in medicine is also highlighted. 

PMID- 24092682
TI  - 2013 classification criteria for systemic sclerosis: an American college of
      rheumatology/European league against rheumatism collaborative initiative.
AB  - OBJECTIVE: The 1980 American College of Rheumatology (ACR) classification
      criteria for systemic sclerosis (SSc) lack sensitivity for early SSc and limited
      cutaneous SSc. The present work, by a joint committee of the ACR and the European
      League Against Rheumatism (EULAR), was undertaken for the purpose of developing
      new classification criteria for SSc. METHODS: Using consensus methods, 23
      candidate items were arranged in a multicriteria additive point system with a
      threshold to classify cases as SSc. The classification system was reduced by
      clustering items and simplifying weights. The system was tested by (1)
      determining specificity and sensitivity in SSc cases and controls with
      scleroderma-like disorders, and (2) validating against the combined view of a
      group of experts on a set of cases with or without SSc. RESULTS: It was
      determined that skin thickening of the fingers extending proximal to the
      metacarpophalangeal joints is sufficient for the patient to be classified as
      having SSc; if that is not present, seven additive items apply, with varying
      weights for each: skin thickening of the fingers, fingertip lesions,
      telangiectasia, abnormal nailfold capillaries, interstitial lung disease or
      pulmonary arterial hypertension, Raynaud's phenomenon, and SSc-related
      autoantibodies. Sensitivity and specificity in the validation sample were,
      respectively, 0.91 and 0.92 for the new classification criteria and 0.75 and 0.72
      for the 1980 ACR classification criteria. All selected cases were classified in
      accordance with consensus-based expert opinion. All cases classified as SSc
      according to the 1980 ACR criteria were classified as SSc with the new criteria,
      and several additional cases were now considered to be SSc. CONCLUSIONS: The
      ACR/EULAR classification criteria for SSc performed better than the 1980 ACR
      criteria for SSc and should allow for more patients to be classified correctly as
      having the disease.

PMID- 24092688
TI  - Resistance exercise induces region-specific adaptations in anterior pituitary
      gland structure and function in rats.
AB  - The anterior pituitary gland (AP) increases growth hormone (GH) secretion in
      response to resistance exercise (RE), but the nature of AP adaptations to RE is
      unknown. To that end, we examined the effects of RE on regional AP somatotroph GH
      release, structure, and relative quantity. Thirty-six Sprague-Dawley rats were
      assigned to one of four groups: 1) no training or acute exercise (NT-NEX); 2) no
      training with acute exercise (NT-EX); 3) resistance training without acute
      exercise (RT-NEX); 4) resistance training with acute exercise (RT-EX). RE
      incorporated 10, 1 m-weighted ladder climbs at an 85 degrees  angle. RT groups
      trained 3 days/wk for 7 wk, progressively. After death, trunk blood was
      collected, and each AP was divided into quadrants (ventral-dorsal and left
      right). We measured: 1) trunk plasma GH; 2) somatotroph GH release; 3)
      somatotroph size; 4) somatotroph secretory content; and 5) percent of AP cells
      identified as somatotrophs. Trunk GH differed by group (NT-NEX, 8.9 +/- 2.4
      MUg/l; RT-NEX, 9.2 +/- 3.5 MUg/l; NT-EX, 15.6 +/- 3.4 MUg/l; RT-EX, 23.4 +/- 4.6
      MUg/l). RT-EX demonstrated greater somatotroph GH release than all other groups,
      predominantly in ventral regions (P < 0.05-0.10). Ventral somatotrophs were
      larger in NT-EX and RT-NEX compared with RT-EX (P < 0.05-0.10). RT-NEX exhibited
      significantly greater secretory granule content than all other groups but in the
      ventral-right region only (P < 0.05-0.10). Our findings indicate reproducible
      patterns of spatially distinct, functionally different somatotroph subpopulations
      in the rat pituitary gland. RE training appears to induce dynamic adaptations in
      somatotroph structure and function. 

PMID- 24092689
TI  - Effects of respiratory time ratio on heart rate variability and spontaneous
      baroreflex sensitivity.
AB  - Paced breathing is a frequently performed technique for cardiovascular autonomic
      studies. The relative timing of inspiration and expiration during paced
      breathing, however, is not consistent. We, therefore, examined whether indexes of
      heart rate variability and spontaneous baroreflex sensitivity would be affected
      by the respiratory time ratio that is set. We studied 14 healthy young adults who
      controlled their breathing rates to either 0.1 or 0.25 Hz in the supine and
      sitting positions. Four different inspiratory-to-expiratory time ratios (I/E)
      (uncontrolled, 1:1, 1:2, and 1:3) were examined for each condition in a
      randomized order. The results showed spectral indexes of heart rate variability
      and spontaneous baroreflex sensitivity were not influenced by the I/E that was
      set during paced breathing under supine and sitting positions. Porta's and
      Guzik's indexes of heart rate asymmetry were also not different at various I/E
      during 0.1-Hz breathing, but had larger values at 1:1 during 0.25-Hz breathing,
      although significant change was found in the sitting position only. At the same
      time, Porta's and Guzik's indexes obtained during 0.1-Hz breathing were greater
      than during 0.25-Hz breathing in both positions. The authors suggest that setting
      the I/E during paced breathing is not necessary when measuring spectral indexes
      of heart rate variability and spontaneous baroreflex sensitivity under the
      conditions used in this study. The necessity of paced breathing for the
      measurement of heart rate asymmetry, however, requires further investigation. 

PMID- 24092690
TI  - 5-HT stimulation of heart rate in Drosophila does not act through cAMP as
      revealed by pharmacogenetics.
AB  - The fruit fly, Drosophila melanogaster, is a good experimental organism to study
      the underlying mechanism of heart rate (HR) regulation. It is already known that
      many neuromodulators (serotonin, dopamine, octopamine, acetylcholine) change the
      HR in Drosophila melanogaster larvae. In this study, we investigated the role of
      cAMP-PKA signaling pathway in HR regulation and 5-HT positive chronotropic
      action. In order to obtain insight into the 5-HT mechanism of action in larvae
      cardiomyocytes, genetic and pharmacological approaches were used. We used
      transgenic flies that expressed the hM4Di receptor [designer receptors
      exclusively activated by designer drugs (DREADDs)] as one tool. Our previous
      results showed that activation of hM4Di receptors (modified muscarinic
      acetylcholine receptors) decreases or arrests the heart from beating. In this
      study, it was hypothesized that the positive chronotropic effect of serotonin [5
      hydroxytryptamine (5-HT)] are mediated by serotonin receptors coupled to the
      adenylyl cyclase pathway and downstream cAMP and PKA activity. Activation of
      hM4Di by clozapine-N-oxide (CNO) was predicted to block the effects of serotonin
      by inhibiting adenylyl cyclase activity through Galphai pathway activation.
      Interestingly, we found here that manipulation of adenylyl cyclase activity and
      cAMP levels had no significant effect on HR. The ability of hM4Di receptor
      activation to slow or stop the heart is therefore likely mediated by activation
      of GIRK channels to produce hyperpolarization of cardiomyocytes, and not through
      inhibition of adenylyl cyclase. 

PMID- 24092691
TI  - The differential effect of metabolic alkalosis on maximum force and rate of force
      development during repeated, high-intensity cycling.
AB  - The purpose of this investigation was to assess the influence of sodium
      bicarbonate supplementation on maximal force production, rate of force
      development (RFD), and muscle recruitment during repeated bouts of high-intensity
      cycling. Ten male and female (n = 10) subjects completed two fixed-cadence, high
      intensity cycling trials. Each trial consisted of a series of 30-s efforts at
      120% peak power output (maximum graded test) that were interspersed with 30-s
      recovery periods until task failure. Prior to each trial, subjects consumed 0.3
      g/kg sodium bicarbonate (ALK) or placebo (PLA). Maximal voluntary contractions
      were performed immediately after each 30-s effort. Maximal force (F max) was
      calculated as the greatest force recorded over a 25-ms period throughout the
      entire contraction duration while maximal RFD (RFD max) was calculated as the
      greatest 10-ms average slope throughout that same contraction. F max declined
      similarly in both the ALK and PLA conditions, with baseline values (ALK: 1,226 +/
      393 N; PLA: 1,222 +/- 369 N) declining nearly 295 +/- 54 N [95% confidence
      interval (CI) = 84-508 N; P < 0.006]. RFD max also declined in both trials;
      however, a differential effect persisted between the ALK and PLA conditions. A
      main effect of condition was observed across the performance time period, with
      RFD max on average higher during ALK (ALK: 8,729 +/- 1,169 N/s; PLA: 7,691 +/-
      1,526 N/s; mean difference between conditions 1,038 +/- 451 N/s, 95% CI = 17
      2,059 N/s; P < 0.048). These results demonstrate a differential effect of
      alkalosis on maximum force vs. maximum rate of force development during a whole
      body fatiguing task.

PMID- 24092692
TI  - Biaxial deformation of collagen and elastin fibers in coronary adventitia.
AB  - The microstructural deformation-mechanical loading relation of the blood vessel
      wall is essential for understanding the overall mechanical behavior of vascular
      tissue in health and disease. We employed simultaneous mechanical loading-imaging
      to quantify in situ deformation of individual collagen and elastin fibers on
      unstained fresh porcine coronary adventitia under a combination of vessel
      inflation and axial extension loading. Specifically, the specimens were imaged
      under biaxial loads to study microscopic deformation-loading behavior of fibers
      in conjunction with morphometric measurements at the zero-stress state. Collagen
      fibers largely orientate in the longitudinal direction, while elastin fibers have
      major orientation parallel to collagen, but with additional orientation angles in
      each sublayer of the adventitia. With an increase of biaxial load, collagen
      fibers were uniformly stretched to the loading direction, while elastin fibers
      gradually formed a network in sublayers, which strongly depended on the initial
      arrangement. The waviness of collagen decreased more rapidly at a circumferential
      stretch ratio of lambdatheta = 1.0 than at lambdatheta = 1.5, while most collagen
      became straightened at lambdatheta = 1.8. These microscopic deformations imply
      that the longitudinally stiffer adventitia is a direct result of initial fiber
      alignment, and the overall mechanical behavior of the tissue is highly dependent
      on the corresponding microscopic deformation of fibers. The microstructural
      deformation-loading relation will serve as a foundation for micromechanical
      models of the vessel wall. 

PMID- 24092693
TI  - Tidal breathing flow measurement in awake young children by using impedance
      pneumography.
AB  - Characteristics of tidal breathing (TB) relate to lung function and may be
      assessed even in young children. Thus far, the accuracy of impedance pneumography
      (IP) in recording TB flows in young children with or without bronchial
      obstruction has not been evaluated. The aim of this study was to evaluate the
      agreement between IP and direct flow measurement with pneumotachograph (PNT) in
      assessing TB flow and flow-derived indices relating to airway obstruction in
      young children. Tidal flow was recorded for 1 min simultaneously with IP and PNT
      during different phases of a bronchial challenge test with methacholine in 21
      wheezy children aged 3 to 7 years. The agreement of IP with PNT was found to be
      excellent in direct flow signal comparison, the mean deviation from linearity
      ranging from 2.4 to 3.1% of tidal peak inspiratory flow. Methacholine-induced
      bronchoconstriction or consecutive bronchodilation induced only minor changes in
      the agreement. Between IP and PNT, the obstruction-related tidal flow indices
      were equally repeatable, and agreement was found to be high, with intraclass
      correlation coefficients for T PTEF/T E, V PTEF/V E, and parameter S being 0.94,
      0.91, and 0.68, respectively. Methacholine-induced changes in tidal flow indices
      showed significant associations with changes in mechanical impedance of the
      respiratory system assessed by the oscillometric technique, with the highest
      correlation found in V PTEF/V E (r = -0.54; P < 0.005 and r = -0.55; P < 0.005 by
      using IP or PNT, respectively). The results indicate that IP can be considered as
      a valid method for recording tidal airflow profiles in young children with
      wheezing disorders.

PMID- 24092694
TI  - Arrangement of sympathetic fibers within the human common peroneal nerve:
      implications for microneurography.
AB  - Recently, interest has grown in the firing patterns of individual or multiunit
      action potential firing patterns in human muscle sympathetic nerve recordings
      using microneurography. Little is known, however, about sympathetic fiber
      distribution in human lower limb nerves that will affect the multiunit
      recordings. Therefore, the purpose of this study was to examine the sympathetic
      fiber distribution within the human common peroneal nerve using
      immunohistochemical techniques (tyrosine hydroxylase, avidin-biotin complex
      technique). Five-micrometer transverse and 10-MUm longitudinal sections, fixed in
      formaldehyde, were obtained from the peroneal nerve that had been harvested from
      three human cadavers (83 +/- 11 yr) within 24 h of death. Samples of rat adrenal
      gland and brain served as controls. Sympathetic fiber arrangement varied between
      left and right nerves of the same donor, and between donors. However, in general,
      sympathetic fibers were dispersed throughout ~25-38 fascicles of the peroneal
      nerve. The fibers were grouped in bundles of ~2-44 axons or expressed
      individually throughout the fascicles, and the distribution was skewed toward
      smaller bundles with median and interquartile ratio values of 5 and 1
      axons/bundle, respectively. These findings confirm the bundled organization of
      sympathetic axons within the peroneal nerve and provide the anatomical basis for
      outcomes in microneurographic studies. 

PMID- 24092696
TI  - Automated fiber-type-specific cross-sectional area assessment and myonuclei
      counting in skeletal muscle.
AB  - Skeletal muscle is an exceptionally adaptive tissue that compromises 40% of
      mammalian body mass. Skeletal muscle functions in locomotion, but also plays
      important roles in thermogenesis and metabolic homeostasis. Thus characterizing
      the structural and functional properties of skeletal muscle is important in many
      facets of biomedical research, ranging from myopathies to rehabilitation sciences
      to exercise interventions aimed at improving quality of life in the face of
      chronic disease and aging. In this paper, we focus on automated quantification of
      three important morphological features of muscle: 1) muscle fiber-type
      composition; 2) muscle fiber-type-specific cross-sectional area, and 3)
      myonuclear content and location. We experimentally prove that the proposed
      automated image analysis approaches for fiber-type-specific assessments and
      automated myonuclei counting are fast, accurate, and reliable. 

PMID- 24092698
TI  - Maternal immunization: an intelligent solution to reduce the hidden burden of
      group B streptococcus perinatal disease.

PMID- 24092700
TI  - Improving scientific communication.

PMID- 24092695
TI  - Activation of upper airway muscles during breathing and swallowing.
AB  - The upper airway is a complex muscular tube that is used by the respiratory and
      digestive systems. The upper airway is invested with several small and
      anatomically peculiar muscles. The muscle fiber orientations and their nervous
      innervation are both extremely complex, and how the activity of the muscles is
      initiated and adjusted during complex behaviors is poorly understood. The bulk of
      the evidence suggests that the entire assembly of tongue and laryngeal muscles
      operate together but differently during breathing and swallowing, like a ballet
      rather than a solo performance. Here we review the functional anatomy of the
      tongue and laryngeal muscles, and their neural innervation. We also consider how
      muscular activity is altered as respiratory drive changes, and briefly address
      upper airway muscle control during swallowing. 

PMID- 24092697
TI  - A selective 5-HT1a receptor agonist improves respiration in a mouse model of Rett
      syndrome.
AB  - Rett syndrome is a neurological disorder caused by loss of function mutations in
      the gene that encodes the DNA binding protein methyl-CpG-binding protein 2
      (Mecp2). A prominent feature of the syndrome is disturbances in respiration
      characterized by frequent apnea and an irregular interbreath cycle. 8-Hydroxy-2
      dipropylaminotetralin has been shown to positively modulate these disturbances
      (Abdala AP, Dutschmann M, Bissonnette JM, Paton JF, Proc Natl Acad Sci U S A 107:
      18208-18213, 2010), but the mode of action is not understood. Here we show that
      the selective 5-HT1a biased agonist 3-chloro-4-fluorophenyl-(4-fluoro-4-{[(5
      methylpyrimidin-2-ylmethyl)-amino]-methyl}-piperidin-1-yl)-methanone (F15599)
      decreases apnea and corrects irregularity in both heterozygous Mecp2-deficient
      female and in Mecp2 null male mice. In whole cell voltage-clamp recordings from
      dorsal raphe neurons, F15599 potently induced an outward current, which was
      blocked by barium, reversed at the potassium equilibrium potential, and was
      antagonized by the 5-HT1a antagonist WAY100135. This is consistent with
      somatodendritic 5-HT1a receptor-mediated activation of G protein-coupled inwardly
      rectifying potassium channels (GIRK). In contrast, F15599 did not activate 5
      HT1b/d receptors that mediate inhibition of glutamate release from terminals in
      the nucleus accumbens by a presynaptic mechanism. Thus F15599 activated
      somatodendritic 5-HT1a autoreceptors, but not axonal 5-HT1b/d receptors. In
      unanesthetized Mecp2-deficient heterozygous female mice, F15599 reduced apnea in
      a dose-dependent manner with maximal effect of 74.5 +/- 6.9% at 0.1 mg/kg and
      improved breath irrregularity. Similarly, in Mecp2 null male mice, apnea was
      reduced by 62 +/- 6.6% at 0.25 mg/kg, and breathing became regular. The results
      indicate respiration is improved with a 5-HT1a agonist that activates GIRK
      channels without affecting neurotransmitter release. 

PMID- 24092705
TI  - Science funding. U.S. shutdown spares an 'essential' few.

PMID- 24092706
TI  - Climate science. The IPCC gains confidence in key forecast.

PMID- 24092708
TI  - Climate science. For researchers, IPCC leaves a deep impression.

PMID- 24092707
TI  - A stronger IPCC report.

PMID- 24092709
TI  - Neuroscience. Brain stimulation sparks 'Machiavellian' choices.

PMID- 24092710
TI  - Evolution. Large-scale gene comparisons boost tree of life studies.

PMID- 24092711
TI  - Biomedicine. NIH seeks better database for genetic diagnosis.

PMID- 24092712
TI  - The art of eradicating polio.

PMID- 24092714
TI  - Land use. Managing forests and fire in changing climates.

PMID- 24092715
TI  - Computer science. Future science.

PMID- 24092716
TI  - Plant science. Small RNA--the secret of noble rot.

PMID- 24092717
TI  - Chemistry. Turn the molecule this way for a faster reaction.

PMID- 24092718
TI  - Epidemiology. Social factors in epidemiology.

PMID- 24092719
TI  - History of science. Public Science 2.0--back to the future.

PMID- 24092720
TI  - Plant science. Fine-tuning photosynthesis.

PMID- 24092721
TI  - Physiology. A looser clock to cure jet lag.

PMID- 24092722
TI  - Social science. A risky science communication environment for vaccines.

PMID- 24092724
TI  - The rise of open access.

PMID- 24092723
TI  - Communication in science pressures and predators. Scientific discourse: buckling
      at the seams. Introduction.

PMID- 24092725
TI  - Who's afraid of peer review?

PMID- 24092726
TI  - The seer of science publishing.

PMID- 24092727
TI  - The power of negative thinking.

PMID- 24092728
TI  - Hey, you've got to hide your work away.

PMID- 24092729
TI  - Cloak-and-dagger publishing.

PMID- 24092730
TI  - Lock up the genome, lock down research?

PMID- 24092732
TI  - What's lost when a meeting goes virtual.

PMID- 24092731
TI  - The annual meeting: improving what isn't broken.

PMID- 24092733
TI  - Meetings that flatter, but may not deliver.

PMID- 24092734
TI  - Great presenters: lighting up the auditorium.

PMID- 24092735
TI  - Gut instinct.

PMID- 24092736
TI  - Scholarly communication: cultural contexts, evolving models.
AB  - Despite predictions that emerging technologies will transform how research is
      conducted, disseminated, and rewarded, why do we see so little actual shift in
      how scholars in the most competitive and aspirant institutions actually
      disseminate their research? I describe research on faculty values and needs in
      scholarly communication that confirm a number of conservative tendencies in
      publishing. These tendencies, influenced by tenure and promotion requirements, as
      well as disciplinary cultures, have both positive and negative consequences.
      Rigorous research could inform development of good practices and policies in
      academic publishing, as well as counter rhetoric concerning the future of peer
      review and scholarly communication. 

PMID- 24092737
TI  - Mice genetically deficient in vasopressin V1a and V1b receptors are resistant to
      jet lag.
AB  - Jet-lag symptoms arise from temporal misalignment between the internal circadian
      clock and external solar time. We found that circadian rhythms of behavior
      (locomotor activity), clock gene expression, and body temperature immediately
      reentrained to phase-shifted light-dark cycles in mice lacking vasopressin
      receptors V1a and V1b (V1a(-/-)V1b(-/-)). Nevertheless, the behavior of V1a(-/
      )V1b(-/-) mice was still coupled to the internal clock, which oscillated normally
      under standard conditions. Experiments with suprachiasmatic nucleus (SCN) slices
      in culture suggested that interneuronal communication mediated by V1a and V1b
      confers on the SCN an intrinsic resistance to external perturbation.
      Pharmacological blockade of V1a and V1b in the SCN of wild-type mice resulted in
      accelerated recovery from jet lag, which highlights the potential of vasopressin
      signaling as a therapeutic target for management of circadian rhythm
      misalignment, such as jet lag and shift work. 

PMID- 24092738
TI  - Selective gas transport through few-layered graphene and graphene oxide
      membranes.
AB  - Graphene is a distinct two-dimensional material that offers a wide range of
      opportunities for membrane applications because of ultimate thinness,
      flexibility, chemical stability, and mechanical strength. We demonstrate that few
      and several-layered graphene and graphene oxide (GO) sheets can be engineered to
      exhibit the desired gas separation characteristics. Selective gas diffusion can
      be achieved by controlling gas flow channels and pores via different stacking
      methods. For layered (3- to 10-nanometer) GO membranes, tunable gas transport
      behavior was strongly dependent on the degree of interlocking within the GO
      stacking structure. High carbon dioxide/nitrogen selectivity was achieved by well
      interlocked GO membranes in high relative humidity, which is most suitable for
      postcombustion carbon dioxide capture processes, including a humidified feed
      stream. 

PMID- 24092739
TI  - Ultrathin, molecular-sieving graphene oxide membranes for selective hydrogen
      separation.
AB  - Ultrathin, molecular-sieving membranes have great potential to realize high-flux,
      high-selectivity mixture separation at low energy cost. Current microporous
      membranes [pore size < 1 nanometer (nm)], however, are usually relatively thick.
      With the use of current membrane materials and techniques, it is difficult to
      prepare microporous membranes thinner than 20 nm without introducing extra
      defects. Here, we report ultrathin graphene oxide (GO) membranes, with thickness
      approaching 1.8 nm, prepared by a facile filtration process. These membranes
      showed mixture separation selectivities as high as 3400 and 900 for H2/CO2 and
      H2/N2 mixtures, respectively, through selective structural defects on GO. 

PMID- 24092740
TI  - Specific chemical reactivities of spatially separated 3-aminophenol conformers
      with cold Ca+ ions.
AB  - Many molecules exhibit multiple rotational isomers (conformers) that interconvert
      thermally and are difficult to isolate. Consequently, a precise characterization
      of their role in chemical reactions has proven challenging. We have probed the
      reactivity of specific conformers by using an experimental technique based on
      their spatial separation in a molecular beam by electrostatic deflection. The
      separated conformers react with a target of Coulomb-crystallized ions in a trap.
      In the reaction of Ca(+) with 3-aminophenol, we find a twofold larger rate
      constant for the cis compared with the trans conformer (differentiated by the O-H
      bond orientation). This result is explained by conformer-specific differences in
      the long-range ion-molecule interaction potentials. Our approach demonstrates the
      possibility of controlling reactivity through selection of conformational states.

PMID- 24092741
TI  - Following gene duplication, paralog interference constrains transcriptional
      circuit evolution.
AB  - Most models of gene duplication assume that the ancestral functions of the
      preduplication gene are independent and can therefore be neatly partitioned
      between descendant paralogs. However, many gene products, such as transcriptional
      regulators, are components within cooperative assemblies; here, we show that a
      natural consequence of duplication and divergence of such proteins can be
      competitive interference between the paralogs. Our example is based on the
      duplication of the essential MADS-box transcriptional regulator Mcm1, which is
      found in all fungi and regulates a large set of genes. We show that a set of
      historical amino acid sequence substitutions minimized paralog interference in
      contemporary species and, in doing so, increased the molecular complexity of this
      gene regulatory network. We propose that paralog interference is a common
      constraint on gene duplicate evolution, and its resolution, which can generate
      additional regulatory complexity, is needed to stabilize duplicated genes in the
      genome. 

PMID- 24092742
TI  - Surviving in a marine desert: the sponge loop retains resources within coral
      reefs.
AB  - Ever since Darwin's early descriptions of coral reefs, scientists have debated
      how one of the world's most productive and diverse ecosystems can thrive in the
      marine equivalent of a desert. It is an enigma how the flux of dissolved organic
      matter (DOM), the largest resource produced on reefs, is transferred to higher
      trophic levels. Here we show that sponges make DOM available to fauna by rapidly
      expelling filter cells as detritus that is subsequently consumed by reef fauna.
      This "sponge loop" was confirmed in aquarium and in situ food web experiments,
      using (13)C- and (15)N-enriched DOM. The DOM-sponge-fauna pathway explains why
      biological hot spots such as coral reefs persist in oligotrophic seas--the reef's
      paradox--and has implications for reef ecosystem functioning and conservation
      strategies.

PMID- 24092743
TI  - Allele-specific silencing of mutant Myh6 transcripts in mice suppresses
      hypertrophic cardiomyopathy.
AB  - Dominant mutations in sarcomere proteins such as the myosin heavy chains (MHC)
      are the leading genetic causes of human hypertrophic cardiomyopathy (HCM) and
      dilated cardiomyopathy. We found that expression of the HCM-causing cardiac MHC
      gene (Myh6) R403Q mutation in mice can be selectively silenced by an RNA
      interference (RNAi) cassette delivered by an adeno-associated virus vector. RNAi
      transduced MHC(403/+) mice developed neither hypertrophy nor myocardial fibrosis,
      the pathologic manifestations of HCM, for at least 6 months. Because inhibition
      of HCM was achieved by only a 25% reduction in the levels of the mutant
      transcripts, we suggest that the variable clinical phenotype in HCM patients
      reflects allele-specific expression and that partial silencing of mutant
      transcripts may have therapeutic benefit. 

PMID- 24092744
TI  - Fungal small RNAs suppress plant immunity by hijacking host RNA interference
      pathways.
AB  - Botrytis cinerea, the causative agent of gray mold disease, is an aggressive
      fungal pathogen that infects more than 200 plant species. Here, we show that some
      B. cinerea small RNAs (Bc-sRNAs) can silence Arabidopsis and tomato genes
      involved in immunity. These Bc-sRNAs hijack the host RNA interference (RNAi)
      machinery by binding to Arabidopsis Argonaute 1 (AGO1) and selectively silencing
      host immunity genes. The Arabidopsis ago1 mutant exhibits reduced susceptibility
      to B. cinerea, and the B. cinerea dcl1 dcl2 double mutant that can no longer
      produce these Bc-sRNAs displays reduced pathogenicity on Arabidopsis and tomato.
      Thus, this fungal pathogen transfers "virulent" sRNA effectors into host plant
      cells to suppress host immunity and achieve infection, which demonstrates a
      naturally occurring cross-kingdom RNAi as an advanced virulence mechanism. 

PMID- 24092745
TI  - Quantifying long-term scientific impact.
AB  - The lack of predictability of citation-based measures frequently used to gauge
      impact, from impact factors to short-term citations, raises a fundamental
      question: Is there long-term predictability in citation patterns? Here, we derive
      a mechanistic model for the citation dynamics of individual papers, allowing us
      to collapse the citation histories of papers from different journals and
      disciplines into a single curve, indicating that all papers tend to follow the
      same universal temporal pattern. The observed patterns not only help us uncover
      basic mechanisms that govern scientific impact but also offer reliable measures
      of influence that may have potential policy implications. 

PMID- 24092747
TI  - Small, dense high-density lipoprotein-3 particles are enriched in negatively
      charged phospholipids: relevance to cellular cholesterol efflux, antioxidative,
      antithrombotic, anti-inflammatory, and antiapoptotic functionalities.
AB  - OBJECTIVE: High-density lipoprotein (HDL) displays multiple atheroprotective
      activities and is highly heterogeneous in structure, composition, and function;
      the molecular determinants of atheroprotective functions of HDL are incompletely
      understood. Because phospholipids represent a major bioactive lipid component of
      HDL, we characterized the phosphosphingolipidome of major normolipidemic HDL
      subpopulations and related it to HDL functionality. APPROACH AND RESULTS: Using
      an original liquid chromatography-mass spectrometry/mass spectrometry methodology
      for phospholipid and sphingolipid profiling, 162 individual molecular lipid
      species were quantified across the 9 lipid subclasses, in the order of decreasing
      abundance,
      phosphatidylcholine>sphingomyelin>lysophosphatidylcholine>phosphatidylethanolamin
      >phosphatidylinositol>ceramide>phosphatidylserine>phosphatidylglycerol>phosphatid
      c acid. When data were expressed relative to total lipid, the contents of
      lysophosphatidylcholine and of negatively charged phosphatidylserine and
      phosphatidic acid increased progressively with increase in hydrated density of
      HDL, whereas the proportions of sphingomyelin and ceramide decreased. Key
      biological activities of HDL subpopulations, notably cholesterol efflux capacity
      from human THP-1 macrophages, antioxidative activity toward low-density
      lipoprotein oxidation, antithrombotic activity in human platelets, cell-free anti
      inflammatory activity, and antiapoptotic activity in endothelial cells, were
      predominantly associated with small, dense, protein-rich HDL3. The biological
      activities of HDL particles were strongly intercorrelated, exhibiting significant
      correlations with multiple components of the HDL phosphosphingolipidome.
      Specifically, the content of phosphatidylserine revealed positive correlations
      with all metrics of HDL functionality, reflecting enrichment of
      phosphatidylserine in small, dense HDL3. CONCLUSIONS: Our structure-function
      analysis thereby reveals that the HDL lipidome may strongly affect
      atheroprotective functionality.

PMID- 24092748
TI  - Therapeutic efficacy of human embryonic stem cell-derived endothelial cells in
      humanized mouse models harboring a human immune system.
AB  - OBJECTIVE: Allogeneic transplantation of human embryonic stem cell (hESC)
      derivatives has the potential to elicit the patient's immune response and lead to
      graft rejection. Although hESCs and their derivatives have been shown to have
      advantageous immune properties in vitro, such observations could not be
      determined experimentally in vivo because of ethical and technical constraints.
      However, the generation of humanized mice (hu-mice) harboring a human immune
      system has provided a tool to perform in vivo immunologic studies of human cells
      and tissues. Using this model, we sought to examine the therapeutic potential of
      hESC-derived endothelial cells, human embryonic fibroblasts, and cord blood
      derived endothelial progenitor cells in a human immune system environment.
      APPROACH AND RESULTS: All cell types transplanted in hu-mice showed significantly
      reduced cell survival during the first 14 days post-transplantation compared with
      that observed in immunodeficient mice. During this period, no observable
      therapeutic effects were detected in the hindlimb ischemic mouse models. After
      this point, the cells demonstrated improved survival and contributed to a long
      term improvement in blood perfusion. All cell types showed reduced therapeutic
      efficacy in hu-mice compared with NOD scid IL2 receptor gamma chain knockout
      mice. Interestingly, the eventual improvement in blood flow caused by the hESC
      derived endothelial cells in hu-mice was not much lower than that observed in NOD
      scid IL2 receptor gamma chain knockout mice. CONCLUSIONS: These findings suggest
      that hESC derivatives may be considered a good source for cell therapy and that
      hu-mice could be used as a preclinical in vivo animal model for the evaluation of
      therapeutic efficacy to predict the outcomes of human clinical trials.

PMID- 24092749
TI  - Novel family of insect salivary inhibitors blocks contact pathway activation by
      binding to polyphosphate, heparin, and dextran sulfate.
AB  - OBJECTIVE: Polyphosphate and heparin are anionic polymers released by activated
      mast cells and platelets that are known to stimulate the contact pathway of
      coagulation. These polymers promote both the autoactivation of factor XII and the
      assembly of complexes containing factor XI, prekallikrein, and high-molecular
      weight kininogen. We are searching for salivary proteins from blood-feeding
      insects that counteract the effect of procoagulant and proinflammatory factors in
      the host, including elements of the contact pathway. APPROACH AND RESULTS: Here,
      we evaluate the ability of the sand fly salivary proteins, PdSP15a and PdSP15b,
      to inhibit the contact pathway by disrupting binding of its components to anionic
      polymers. We attempt to demonstrate binding of the proteins to polyphosphate,
      heparin, and dextran sulfate. We also evaluate the effect of this binding on
      contact pathway reactions. We also set out to determine the x-ray crystal
      structure of PdSP15b and examine the determinants of relevant molecular
      interactions. Both proteins bind polyphosphate, heparin, and dextran sulfate with
      high affinity. Through this mechanism they inhibit the autoactivation of factor
      XII and factor XI, the reciprocal activation of factor XII and prekallikrein, the
      activation of factor XI by thrombin and factor XIIa, the cleavage of high
      molecular-weight kininogen in plasma, and plasma extravasation induced by
      polyphosphate. The crystal structure of PdSP15b contains an amphipathic helix
      studded with basic side chains that forms the likely interaction surface.
      CONCLUSIONS: The results of these studies indicate that the binding of anionic
      polymers by salivary proteins is used by blood feeders as an antihemostatic/anti
      inflammatory mechanism.

PMID- 24092750
TI  - Plasma lipoprotein(a) concentration predicts future coronary and cardiovascular
      events in patients with stable coronary heart disease.
AB  - OBJECTIVE: Association between lipoprotein(a) (Lp(a)) level and a first-ever
      coronary (CHD) event is recognized. Less is evident in patients with overt CHD
      and stable symptoms in whom we investigated associations between Lp(a) and future
      events. APPROACH AND RESULTS: Relationships between Lp(a) concentration and CHD
      and cardiovascular disease outcomes during 6 years' median follow-up were
      evaluated in the Long-Term Intervention with Pravastatin in Ischaemic Disease
      (LIPID) study. Lp(a) concentrations were measured in plasma from 7863 patients
      who had sustained a previous coronary event and been randomized to pravastatin or
      placebo. Lp(a) levels were categorized by lowest half, third quartile, 75th to
      90th percentile, and highest decile. The prognostic value of Lp(a) on outcomes
      was assessed by fitting a Cox proportional-hazards model after adjustment for
      other risk factors and baseline cardiovascular disorders. The prognostic value of
      a change in Lp(a) at year 1 categorized by quartiles was assessed using Cox
      regression in a landmark model incorporating the above factors and baseline
      levels. Baseline Lp(a) concentration was associated with total CHD events
      (P<0.001), total cardiovascular disease events (P=0.002), and coronary events
      (P=0.03). Greatest risk occurred at >73 mg/dL, upper decile. For events after
      year 1, an increase in Lp(a) at 1 year was associated with adverse outcomes for
      total CHD events and total cardiovascular disease events (P=0.002 each).
      CONCLUSIONS: In the LIPID study, baseline Lp(a) was associated with future
      cardiovascular disease and CHD events. Increased Lp(a) concentrations after 1
      year were also associated with future events, supporting measurement of Lp(a) for
      risk assessment of patients with known CHD.

PMID- 24092751
TI  - Shades of grey.

PMID- 24092752
TI  - NOD2-nitric oxide-responsive microRNA-146a activates Sonic hedgehog signaling to
      orchestrate inflammatory responses in murine model of inflammatory bowel disease.
AB  - Inflammatory bowel disease (IBD) is a debilitating chronic inflammatory disorder
      of the intestine. The interactions between enteric bacteria and genetic
      susceptibilities are major contributors of IBD etiology. Although genetic
      variants with loss or gain of NOD2 functions have been linked to IBD
      susceptibility, the mechanisms coordinating NOD2 downstream signaling, especially
      in macrophages, during IBD pathogenesis are not precisely identified. Here,
      studies utilizing the murine dextran sodium sulfate model of colitis revealed the
      crucial roles for inducible nitric-oxide synthase (iNOS) in regulating
      pathophysiology of IBDs. Importantly, stimulation of NOD2 failed to activate
      Sonic hedgehog (SHH) signaling in iNOS null macrophages, implicating NO mediated
      cross-talk between NOD2 and SHH signaling. NOD2 signaling up-regulated the
      expression of a NO-responsive microRNA, miR-146a, that targeted NUMB gene and
      alleviated the suppression of SHH signaling. In vivo and ex vivo studies
      confirmed the important roles for miR-146a in amplifying inflammatory responses.
      Collectively, we have identified new roles for miR-146a that established novel
      cross-talk between NOD2-SHH signaling during gut inflammation. Potential
      implications of these observations in therapeutics could increase the possibility
      of defining and developing better regimes to treat IBD pathophysiology. 

PMID- 24092753
TI  - Atypical protein kinase Clambda is critical for growth factor receptor-induced
      dorsal ruffle turnover and cell migration.
AB  - Galpha13, a member of the heterotrimeric G proteins, is critical for actin
      cytoskeletal reorganization and cell migration. Previously we have shown that
      Galpha13 is essential for both G protein-coupled receptor and receptor tyrosine
      kinase-induced actin cytoskeletal reorganization such as dynamic dorsal ruffle
      turnover and cell migration. Ric-8A, a non-receptor guanine nucleotide exchange
      factor for some heterotrimeric G proteins, is critical for coupling receptor
      tyrosine kinases to Galpha13. Here, we show that PDGF can induce phosphorylation
      of Ric-8A. Atypical protein kinase Clambda (aPKClambda) is required for Ric-8A
      phosphorylation. Furthermore, aPKClambda is required for PDGF-induced dorsal
      ruffle turnover and cell migration as demonstrated by both down-regulation of
      aPKClambda protein levels in cells by RNA interference and by studies in
      aPKClambda knock-out cells. Moreover, phosphorylation of Ric-8A modulates its
      subcellular localization. Hence, aPKClambda is critical for PDGF-induced actin
      cytoskeletal reorganization and cell migration. 

PMID- 24092754
TI  - Phosphorylation at tyrosine 262 promotes GADD34 protein turnover.
AB  - In mammalian cells, metabolic and environmental stress increases the
      phosphorylation of the eukaryotic translational initiation factor, eIF2alpha, and
      attenuates global protein synthesis. Subsequent transcriptional activation of
      GADD34 assembles an eIF2alpha phosphatase that feeds back to restore mRNA
      translation. Active proteasomal degradation of GADD34 protein then reestablishes
      the sensitivity of cells to subsequent bouts of stress. Mass spectrometry
      established GADD34 phosphorylation on multiple serines, threonines, and
      tyrosines. Phosphorylation at tyrosine 262 enhanced the rate of the GADD34
      protein turnover. Substrate-trapping studies identified TC-PTP (PTPN2) as a
      potential GADD34 phosphatase, recognizing phosphotyrosine 262. Reduced GADD34
      protein levels in TC-PTP-null MEFs following ER stress emphasized the importance
      of TC-PTP in determining the cellular levels of GADD34 protein. The
      susceptibility of TC-PTP-null MEFs to ER stress-induced apoptosis was
      significantly ameliorated by ectopic expression of GADD34. The data suggested
      that GADD34 phosphorylation on tyrosine 262 modulates endoplasmic reticulum
      stress signaling and cell fate. 

PMID- 24092755
TI  - Human eukaryotic initiation factor 4G (eIF4G) protein binds to eIF3c, -d, and -e
      to promote mRNA recruitment to the ribosome.
AB  - Recruitment of mRNA to the 40S ribosomal subunit requires the coordinated
      interaction of a large number of translation initiation factors. In mammals, the
      direct interaction between eukaryotic initiation factor 4G (eIF4G) and eIF3 is
      thought to act as the molecular bridge between the mRNA cap-binding complex and
      the 40S subunit. A discrete ~90 amino acid domain in eIF4G is responsible for
      binding to eIF3, but the identity of the eIF3 subunit(s) involved is less clear.
      The eIF3e subunit has been shown to directly bind eIF4G, but the potential role
      of other eIF3 subunits in stabilizing this interaction has not been investigated.
      It is also not clear if the eIF4A helicase plays a role in stabilizing the
      interaction between eIF4G and eIF3. Here, we have used a fluorescence anisotropy
      assay to demonstrate that eIF4G binds to eIF3 independently of eIF4A binding to
      the middle region of eIF4G. By using a site-specific cross-linking approach, we
      unexpectedly show that the eIF4G-binding surface in eIF3 is comprised of the -c, 
      d and -e subunits. Screening multiple cross-linker positions reveals that eIF4G
      contains two distinct eIF3-binding subdomains within the previously identified
      eIF3-binding domain. Finally, by employing an eIF4G-dependent translation assay,
      we establish that both of these subdomains are required for efficient mRNA
      recruitment to the ribosome and stimulate translation. Our study reveals
      unexpected complexity to the eIF3-eIF4G interaction that provides new insight
      into the regulation of mRNA recruitment to the human ribosome. 

PMID- 24092757
TI  - Sites under positive selection modulate the RNA silencing suppressor activity of
      rice yellow mottle virus movement protein P1.
AB  - RNA silencing is a eukaryotic mechanism for RNA-based gene regulation that plays
      an essential role in diverse biological processes, such as defence against viral
      infections. The P1 of rice yellow mottle virus (RYMV) is a movement protein and
      displays RNA silencing suppression activity with variable efficiency, depending
      on the origin of the isolates. In this study, the positive selection pressure
      acting on the P1 protein gene was assessed. A site-by-site analysis of the dN/dS
      ratio was performed and 18 positively selected sites were identified. Four of
      these were mutated, and the ability to suppress RNA silencing was evaluated for
      the resulting mutants in a transient expression assay. All mutations affected
      quantitatively RNA silencing suppression, one caused a significant decrease in
      the activity and three significantly increased it. This work demonstrates, for
      what is to the best of our knowledge the first time, that the RYMV gene encoding
      the P1 RNA silencing suppressor is under adaptive evolution. 

PMID- 24092756
TI  - Molecular basis of cannabinoid CB1 receptor coupling to the G protein
      heterotrimer Galphaibetagamma: identification of key CB1 contacts with the C
      terminal helix alpha5 of Galphai.
AB  - The cannabinoid (CB1) receptor is a member of the rhodopsin-like G protein
      coupled receptor superfamily. The human CB1 receptor, which is among the most
      expressed receptors in the brain, has been implicated in several disease states,
      including drug addiction, anxiety, depression, obesity, and chronic pain.
      Different classes of CB1 agonists evoke signaling pathways through the activation
      of specific subtypes of G proteins. The molecular basis of CB1 receptor coupling
      to its cognate G protein is unknown. As a first step toward understanding CB1
      receptor-mediated G protein signaling, we have constructed a ternary complex
      structural model of the CB1 receptor and Gi heterotrimer (CB1-Gi), guided by the
      x-ray structure of beta2-adrenergic receptor (beta2AR) in complex with Gs
      (beta2AR-Gs), through 824-ns duration molecular dynamics simulations in a fully
      hydrated 1-palmitoyl-2-oleoyl-sn-glycero-3-phosphocholine bilayer environment. We
      identified a group of residues at the juxtamembrane regions of the intracellular
      loops 2 and 3 (IC2 and IC3) of the CB1 receptor, including Ile-218(3.54), Tyr
      224(IC2), Asp-338(6.30), Arg-340(6.32), Leu-341(6.33), and Thr-344(6.36), as
      potential key contacts with the extreme C-terminal helix alpha5 of Galphai. Ala
      mutations of these residues at the receptor-Gi interface resulted in little G
      protein coupling activity, consistent with the present model of the CB1-Gi
      complex, which suggests tight interactions between CB1 and the extreme C-terminal
      helix alpha5 of Galphai. The model also suggests that unique conformational
      changes in the extreme C-terminal helix alpha5 of Galpha play a crucial role in
      the receptor-mediated G protein activation. 

PMID- 24092758
TI  - A single amino acid in the F2 subunit of respiratory syncytial virus fusion
      protein alters growth and fusogenicity.
AB  - Respiratory syncytial virus (RSV) causes severe lower respiratory tract infection
      in children, especially in infants less than 1 year of age. There are currently
      no licensed vaccines against RSV. rA2DeltaM2-2 is a promising live-attenuated
      vaccine candidate that is currently being evaluated in the clinic. Attenuation of
      rA2DeltaM2-2 is achieved by a single deletion of the M2-2 gene, which disrupts
      the balance between viral transcription and replication. Whilst performing a
      manufacturing feasibility study in a serum-free adapted Vero cell line,
      differences in growth kinetics and cytopathic effect (CPE) were identified
      between two rA2DeltaM2-2 vaccine candidates. Comparative sequence analysis
      identified four amino acid differences between the two vaccine viruses.
      Recombinant rA2DeltaM2-2 viruses carrying each of the four amino acid differences
      identified a K66E mutation in the F2 fragment of the fusion (F) protein as the
      cause of the growth and CPE differences. Syncytium-formation experiments with RSV
      F protein carrying mutations at aa 66 suggested that a change in charge at this
      residue within the F2 fragment can have a significant impact on fusion. 

PMID- 24092759
TI  - Development of chimaeric West Nile virus attenuated vaccine candidate based on
      the Japanese encephalitis vaccine strain SA14-14-2.
AB  - Mosquito-borne flaviviruses include a large group of important human medical
      pathogens. Several chimaeric flaviviruses have been constructed, and show
      potential for vaccine development. Although Japanese encephalitis virus (JEV)
      live vaccine SA14-14-2 has been widely used with ideal safety and efficacy
      profiles, no chimaeric flavivirus based on the JEV vaccine has been described to
      date. Based on the reverse genetic system of the JEV vaccine SA14-14-2, a novel
      live chimaeric flavivirus carrying the protective antigens of West Nile virus
      (WNV) was constructed and recovered in this study. The resulting chimaera
      (ChinWNV) replicated efficiently in both mammalian and mosquito cells and
      possessed genetic stability after in vitro serial passaging. ChinWNV exhibited a
      small-plaque phenotype, and its replication was significantly restricted in mouse
      peripheral blood and brain compared with parental WNV. Importantly, ChinWNV was
      highly attenuated with regard to both neurovirulence and neuroinvasiveness in
      mice. Furthermore, a single ChinWNV immunization stimulated robust WNV-specific
      adaptive immune responses in mice, conferring significant protection against
      lethal WNV infection. Our results demonstrate that chimaeric flaviviruses based
      on the JEV vaccine can serve as a powerful platform for vaccine development, and
      that ChinWNV represents a potential WNV vaccine candidate that merits further
      development. 

PMID- 24092760
TI  - Imaging of upper urinary tract cancer: using conventional MRI and diffusion
      weighted MRI with different b values.
AB  - BACKGROUND: Diffusion-weighted magnetic resonance imaging (DW-MRI) has been
      considered to be useful in diagnosing upper urinary tract (UUT) disease; however,
      the value of DW-MRI with different b values has not been reported. PURPOSE: To
      evaluate the performance of using conventional MRI alone and in combination with
      DWI with different b values in diagnosing UUT cancer. MATERIAL AND METHODS:
      Seventy patients with suspected UUT cancer underwent conventional MRI (T1
      weighted and T2-weighted) and DW-MRI (b = 500 and 1500 s/mm(2)) on a 3 T-MRI
      scanner. The ureteroscopic and histopathologic findings were compared with the
      imaging findings. The utility of detecting UUT cancer using conventional MRI (set
      A), combined DW-MRI (b = 500 s/mm(2)) and conventional MRI (set B), and combined
      DW-MRI (b = 1500 s/mm(2)) and conventional MRI (set C) were independently
      evaluated by two readers. RESULTS: A total of 32 patients had verified cancer; 23
      patients had benign UUT diseases, and 15 had no abnormality. Sets B and C had
      significantly improved diagnostic accuracy for UUT cancer compared with set A;
      the specificity in diagnosing UUT cancer was significantly improved when using
      set C compared with sets A and B. In patients without UUT obstructions, improved
      sensitivity and accuracy in diagnosis was achieved when using sets B and C
      compared with set A. CONCLUSION: Using DW-MRI in combination with conventional
      MRI provides increased diagnostic accuracy and sensitivity in patients without
      UUT obstruction. The combination of conventional MRI and DW-MRI with a higher b
      value (1500 s/mm(2)) improved the specificity in diagnosing UUT cancer compared
      to conventional sequences and DW-MRI with a lower b value (500 s/mm(2)).

PMID- 24092761
TI  - Reliability of on-call radiology residents' interpretation of 64-slice CT
      pulmonary angiography for the detection of pulmonary embolism.
AB  - BACKGROUND: Computed tomography (CT) angiography for pulmonary embolism (PE) is
      the present standard for diagnosing PE. In many teaching hospitals, radiology
      residents are the first to review the case and to make an initial interpretation
      of the images. Accurate diagnosis of PE is crucial, especially in the emergency
      care setting. PURPOSE: To evaluate the discrepancies between resident and staff
      interpretations of 64-slice CT angiogram for PE. MATERIAL AND METHODS:
      Discrepancies between the preliminary reports by the on-call radiology resident
      were compared to the final report by the staff radiologist in 215 consecutive
      cases of 64-slice CT angiogram performed for PE, from May 2005 to March 2008.
      RESULTS: Discrepancies were noted in 25 of the 215 studies (11.6%). These
      residents' discrepancies consisted of three false-positive, four false-negative,
      and 18 equivocal cases. There was a decrease in the discrepancy rate from the
      second year to the fifth year of training by approximately 60%. CONCLUSION: The
      rate of discrepancy fell steeply between the second and fifth year of the
      residents training from 18.5% to 6.9%. Our study suggests that it is reasonable
      to have on-call radiology residents perform the preliminary interpretations of 64
      slice CT for PE studies.

PMID- 24092763
TI  - Ultramarathon run markedly reduces plasma sphingosine-1-phosphate concentration.
AB  - We have previously shown that acute exercise increases the level of sphingosine-1
      phosphate (S1P) in plasma and ceramide in erythrocytes of untrained subjects. The
      aim of the current study was to examine the effect of ultramarathon run on the
      plasma and erythrocyte levels of the following bioactive sphingolipids: S1P,
      sphinganine-1-phosphate (SA1P), sphingosine, sphinganine, and ceramide. Blood
      samples were collected from seven male amateur runners participating in a 48-hr
      ultramarathon race before the run, after 24 and 48 hr of running, and following
      24 and 48 hr of recovery. The sphingolipids were quantified by means of HPLC.
      Sustained running for 48 hr resulted in a progressive decline in plasma S1P to a
      level significantly lower than at prerace, and then remained stable over the next
      48 hr of recovery. In erythrocytes, S1P content was stable until 24 hr of
      recovery, then rose abruptly to reach peak values after 48 hr of recovery. The
      plasma level of SA1P decreased progressively during the competition and remained
      unchanged over the recovery. In erythrocytes, the level of SA1P increased after
      24 hr running and normalized thereafter. The level of ceramide, both in plasma
      and erythrocytes, was not significantly affected by the ultraendurance run. We
      speculate that reduction in plasma level of S1P during and after the run reduces
      its biological actions and might be responsible for some negative side-effects of
      the ultraendurance effort. 

PMID- 24092762
TI  - A national quality assurance survey of Neisseria gonorrhoeae testing.
AB  - The aims of this study were to (1) conduct a national survey of Neisseria
      gonorrhoeae identification by National Neisseria Network (NNN) reference
      laboratories contributing data to the Australian Gonococcal Surveillance
      Programme and (2) determine the prevalence in Australia of strains of N.
      gonorrhoeae lacking gene sequences commonly targeted by in-house PCR assays for
      confirmation of gonococcal nucleic acid amplification tests. Gonococcal clinical
      isolates referred to NNN laboratories for the first half of 2012 were screened
      using in-house real-time PCR assays targeting multicopy opa, porA pseudogene and
      cppB genes. There were 2455 clinical gonococcal isolates received in the study
      period; 98.6 % (2420/2455) of isolates harboured all three gene targets, 0.12 %
      (3/2455) were porA-negative, 0.04 % (1/2455) opa-negative and 1.14 % (28/2455)
      cppB-negative by PCR. Notably, no isolates were simultaneously negative for two
      targets. However, three isolates failed to be amplified by all three PCR methods,
      one isolate of which was shown to be a commensal Neisseria strain by 16S rRNA
      sequencing. Using PCR as the reference standard the results showed that (1)
      identification of N. gonorrhoeae isolates by NNN laboratories was highly specific
      (99.96 %) and (2) strains of N. gonorrhoeae lacking gene sequences commonly
      targeted by in-house PCR assays are present but not widespread throughout
      Australia at this point in time.

PMID- 24092764
TI  - Role ambiguity, role conflict, or burnout: are these areas of concern for
      Australian palliative care volunteers? Pilot study results.
AB  - OBJECTIVE: To determine whether burnout, role ambiguity, or conflict affects
      Australian hospice volunteers. METHOD: Hospice volunteers (n = 120) were invited
      to participate in this pilot survey. Quantitative data were analyzed using
      descriptive statistics, while the free-text responses were analyzed using
      thematic content analysis. The Strengthening the Reporting of Observational
      Studies in Epidemiology (STROBE) Guidelines have been used to report this data.
      RESULTS: A total of 97 participants completed the survey. The majority were
      middle-aged women who had been palliative care volunteers for more than 7 years
      and volunteered 14 hours/week (median). Participants reported low levels of role
      ambiguity (x = 8.4, standard deviation [SD] +/-3.0) and conflict (x = 9.8, SD +/
      3.4) and described enjoying their volunteering and having no symptoms of burnout
      (76%). SIGNIFICANCE: Active hospice volunteers report low levels of role
      ambiguity, conflict, and burnout. Adopting a range of self-care strategies and
      working within a structured volunteer program appear to be important protective
      factors.

PMID- 24092765
TI  - A systematic review of dietary protein during caloric restriction in resistance
      trained lean athletes: a case for higher intakes.
AB  - Caloric restriction occurs when athletes attempt to reduce body fat or make
      weight. There is evidence that protein needs increase when athletes restrict
      calories or have low body fat. PURPOSE: The aims of this review were to evaluate
      the effects of dietary protein on body composition in energy-restricted
      resistance-trained athletes and to provide protein recommendations for these
      athletes. METHODS: Database searches were performed from earliest record to July
      2013 using the terms protein, and intake, or diet, and weight, or train, or
      restrict, or energy, or strength, and athlete. Studies (N = 6) needed to use
      adult (>= 18 yrs), energy-restricted, resistance-trained (> 6 months) humans of
      lower body fat (males <= 23% and females <= 35%) performing resistance training.
      Protein intake, fat free mass (FFM) and body fat had to be reported. RESULTS:
      Body fat percentage decreased (0.5-6.6%) in all study groups (N = 13) and FFM
      decreased (0.3-2.7kg) in nine of 13. Six groups gained, did not lose, or lost
      nonsignificant amounts of FFM. Five out of these six groups were among the
      highest in body fat, lowest in caloric restriction, or underwent novel resistance
      training stimuli. However, the one group that was not high in body fat that
      underwent substantial caloric restriction, without novel training stimuli,
      consumed the highest protein intake out of all the groups in this review (2.5
      2.6g/kg). CONCLUSIONS: Protein needs for energy-restricted resistance-trained
      athletes are likely 2.3-3.1g/kg of FFM scaled upwards with severity of caloric
      restriction and leanness.

PMID- 24092766
TI  - iPEAP: integrating multiple omics and genetic data for pathway enrichment
      analysis.
AB  - A challenge in biodata analysis is to understand the underlying phenomena among
      many interactions in signaling pathways. Such study is formulated as the pathway
      enrichment analysis, which identifies relevant pathways functional enriched in
      high-throughput data. The question faced here is how to analyze different data
      types in a unified and integrative way by characterizing pathways that these data
      simultaneously reveal. To this end, we developed integrative Pathway Enrichment
      Analysis Platform, iPEAP, which handles transcriptomics, proteomics, metabolomics
      and GWAS data under a unified aggregation schema. iPEAP emphasizes on the ability
      to aggregate various pathway enrichment results generated in different high
      throughput experiments, as well as the quantitative measurements of different
      ranking results, thus providing the first benchmark platform for integration,
      comparison and evaluation of multiple types of data and enrichment methods.
      AVAILABILITY AND IMPLEMENTATION: iPEAP is freely available at
      http://www.tongji.edu.cn/~qiliu/ipeap.html.

PMID- 24092767
TI  - Nucleocytoplasmic shuttling of IPAS by its unique nuclear import and export
      signals unshared with other HIF-3alpha splice variants.
AB  - Inhibitory Per/Arnt/Sim (PAS) domain protein (IPAS) is a splice variant of
      hypoxia-inducible factor (HIF)-3alpha, and possesses two entirely different
      functions. One is as a transcriptional repressor against HIF-dependent hypoxic
      gene activation. The other is as a pro-apoptotic factor by direct binding to the
      pro-survival protein Bcl-xL and its related proteins on mitochondria. Presently,
      the regulatory mechanism that determines the intracellular distribution of IPAS
      to fulfill each of the two functions is unknown. As a first step towards
      elucidation of the mechanism, nucleocytoplasmic transport signals of IPAS were
      explored. A bipartite-like nuclear localization signal (NLS) was found in the N
      terminal region by the deletion and mutation analysis of EGFP-IPAS. In addition,
      the helix-loop-helix domain showed weak nuclear import/retention activity. A
      leptomycin B-sensitive nuclear export signal (NES) was localized in the C
      terminal region of the protein. A proline-rich region supported the NES activity.
      These NLS and NES are not carried by the other variants of HIF-3alpha due to
      differential exon usage. These results strongly suggest that IPAS is a
      nucleocytoplasmic shuttling protein. 

PMID- 24092746
TI  - Integrative annotation of variants from 1092 humans: application to cancer
      genomics.
AB  - Interpreting variants, especially noncoding ones, in the increasing number of
      personal genomes is challenging. We used patterns of polymorphisms in
      functionally annotated regions in 1092 humans to identify deleterious variants;
      then we experimentally validated candidates. We analyzed both coding and
      noncoding regions, with the former corroborating the latter. We found regions
      particularly sensitive to mutations ("ultrasensitive") and variants that are
      disruptive because of mechanistic effects on transcription-factor binding (that
      is, "motif-breakers"). We also found variants in regions with higher network
      centrality tend to be deleterious. Insertions and deletions followed a similar
      pattern to single-nucleotide variants, with some notable exceptions (e.g.,
      certain deletions and enhancers). On the basis of these patterns, we developed a
      computational tool (FunSeq), whose application to ~90 cancer genomes reveals
      nearly a hundred candidate noncoding drivers. 

PMID- 24092768
TI  - Deregulation of hyaluronan synthesis, degradation and binding promotes breast
      cancer.
AB  - Clinical and experimental data indicate that hyaluronan accumulates in breast
      cancer compared with normal breast epithelium, which correlates to poor
      prognosis. In this review, we discuss the expression of genes encoding enzymes
      that synthesize or degrade hyaluronan, i.e. hyaluronan synthases and
      hyaluronidases or bind hyaluronan, i.e. CD44 and receptor for hyaluronan-mediated
      motility (RHAMM, also designated as HMMR or CD168), in relation to breast cancer
      progression. Hyaluronan and hyaluronan receptors have multi-faceted roles in
      signalling events in breast cancer. A better understanding of the molecular
      mechanisms underlying these signalling pathways is highly warranted and may lead
      to improvement of cancer treatment. 

PMID- 24092769
TI  - The effects of carbohydrate loading 48 hours before a simulated squash match.
AB  - The aim of this study was to ascertain whether a high carbohydrate diet in the
      days before movement patterns simulating a squash match would increase
      carbohydrate oxidation during the match, and alter physical performance. Nine New
      Zealand level squash players were recruited to complete a simulated squash match
      on two occasions: 1) following a 48-hr high carbohydrate (11.1g.kg-1); and 2)
      following a calorie-matched low carbohydrate (2.1 g.kg-1) diet. The interventions
      were assigned in a randomized, single-blind, cross-over design. The match
      simulation was designed to mimic a five-game match lasting approximately 1 hr.
      Performance was measured as time to complete each game. Expired respiratory gases
      and heart rate were continuously collected throughout the trial using a portable
      gas analysis system. Capillary blood glucose and lactate samples were obtained
      during a 90 s rest period between each game. Rating of perceived exertion was
      also recorded after each set. Respiratory exchange ratio was significantly higher
      during exercise following the high CHO diet (0.80 vs. 0.76) p < .001) and this
      was associated with significantly faster time to complete the games (2340 +/- 189
      s vs. 2416 +/- 128 s, p = .036). Blood glucose and lactate concentrations were
      also significantly higher in the high carbohydrate condition (p = .038 and p =
      .021 respectively). These results suggest that ingestion of a diet high in
      carbohydrate (>10 g/kg body weight) preceding simulated competitive squash
      produces increased rates of carbohydrate oxidation and maintains higher blood
      glucose concentrations. These metabolic effects were associated with improved
      physical performance. 

PMID- 24092770
TI  - Effect of high-intensity intermittent exercise on postprandial plasma
      triacylglycerol in sedentary young women.
AB  - High-intensity intermittent exercise (HIIE) such as the 30-s Wingate test
      attenuates postprandial triacylglycerol (TG), however, the ability of shorter
      versions of HIIE to reduce postprandial TG is undetermined. Thus, the effect of 8
      s sprinting bouts of HIIE on blood TG levels of 12 females after consumption of a
      high-fat meal (HFM) was examined. Twelve young, sedentary women (BMI 25.1 +/- 2.3
      kg/m2; age 21.3 +/- 2.1 years) completed a maximal oxygen uptake test and then on
      different days underwent either an exercise or a no-exercise postprandial TG
      condition. Both conditions involved consuming a HFM after a 12-hr fast. The HFM,
      in milkshake form provided 4170 kJ (993 Kcal) of energy and 98 g fat. Order was
      counter-balanced. In the exercise condition participants completed 20-min of HIIE
      cycling consisting of repeated bouts of 8 s sprint cycling (100-115 rpm) and 12 s
      of active rest (easy pedaling) 14 hr before consuming the HFM. Blood samples were
      collected hourly after the HFM for 4 hr. Total postprandial TG was 13% lower, p =
      .004, in the exercise (5.84 +/- 1.08 mmol L-1 4 h-1) compared with the no
      exercise condition (6.71 +/- 1.63 mmol L-1 4 h-1). In conclusion, HIIE
      significantly attenuated postprandial TG in sedentary young women.

PMID- 24092771
TI  - Lethal mutagenesis failure may augment viral adaptation.
AB  - Lethal mutagenesis, the attempt to extinguish a population by elevating its
      mutation rate, has been endorsed in the virology literature as a promising
      approach for treating viral infections. In support of the concept, in vitro
      studies have forced viral extinction with high doses of mutagenic drugs. However,
      the one known mutagenic drug used on patients commonly fails to cure infections,
      and in vitro studies typically find a wide range of mutagenic conditions
      permissive for viral growth. A key question becomes how subsequent evolution is
      affected if the viral population is mutated but avoids extinction--Is viral
      adaptation augmented rather than suppressed? Here we consider the evolution of
      highly mutated populations surviving mutagenesis, using the DNA phage T7. In
      assays using inhibitory hosts, whenever resistance mutants were observed, the
      mutagenized populations exhibited higher frequencies, but some inhibitors blocked
      plaque formation by even the mutagenized stock. Second, outgrowth of previously
      mutagenized populations led to rapid and potentially complete fitness recovery
      but polymorphism was slow to decay, and mutations exhibited inconsistent patterns
      of change. Third, the combination of population bottlenecks with mutagenesis did
      cause fitness declines, revealing a vulnerability that was not apparent from
      mutagenesis of large populations. The results show that a population surviving
      high mutagenesis may exhibit enhanced adaptation in some environments and
      experience little negative fitness consequences in many others.

PMID- 24092773
TI  - Assessing preschool children's physical activity: how many days of accelerometry
      measurement.
AB  - The purpose of this study was to determine the minimum number of days of
      accelerometry required to estimate accurately MVPA and total PA in 3- to 5-year
      old children. The study examined these metrics for all days, weekdays, and in
      school activities. Study participants were 204 children attending 22 preschools
      who wore accelerometers for at least 6 hr per day for up to 12 days during most
      waking hours. The primary analysis considered the intraclass correlation
      coefficient (ICC) for each metric to estimate the number of days required to
      attain a specified reliability. The ICC estimates are 0.81 for MVPA-all days,
      0.78 for total PA-all days, 0.83 for MVPA weekdays, 0.80 for total PA-weekdays,
      0.81 for in-school MVPA, and 0.84 for in-school total PA. We recommend a full
      seven days of measurement whenever possible, but researchers can achieve
      acceptable reliability with fewer days, as indicated by the Spearman-Brown
      prophecy: 3-4 days for any weekday measure and 5-6 days for the all-days
      measures. 

PMID- 24092772
TI  - The characterization of sponge NLRs provides insight into the origin and
      evolution of this innate immune gene family in animals.
AB  - The "Nucleotide-binding domain and Leucine-rich Repeat" (NLR) genes are a family
      of intracellular pattern recognition receptors (PRR) that are a critical
      component of the metazoan innate immune system, involved in both defense against
      pathogenic microorganisms and in beneficial interactions with symbionts. To
      investigate the origin and evolution of the NLR gene family, we characterized the
      full NACHT domain-containing gene complement in the genome of the sponge,
      Amphimedon queenslandica. As sister group to all animals, sponges are ideally
      placed to inform our understanding of the early evolution of this ancient PRR
      family. Amphimedon queenslandica has a large NACHT domain-containing gene
      complement that is dominated by bona fide NLRs (n = 135) with varied phylogenetic
      histories. Approximately half of these have a tripartite architecture that
      includes an N-terminal CARD or DEATH domain. The multiplicity of the A.
      queenslandica NLR genes and the high variability across the N- and C-terminal
      domains are consistent with involvement in immunity. We also provide new insight
      into the evolution of NLRs in invertebrates through comparative genomic analysis
      of multiple metazoan and nonmetazoan taxa. Specifically, we demonstrate that the
      NLR gene family appears to be a metazoan innovation, characterized by two major
      gene lineages that may have originated with the last common eumetazoan ancestor.
      Subsequent lineage-specific gene duplication, gene loss and domain shuffling all
      have played an important role in the highly dynamic evolutionary history of
      invertebrate NLRs. 

PMID- 24092774
TI  - Patterns of sedentary behavior and weight status among children.
AB  - To make robust conclusions regarding the association between accelerometer
      measured sedentary time and overweight and obesity among children, several gaps
      in the literature must be addressed. The purpose of this study was to examine
      associations between sedentary time, weekday sedentary time, weekend sedentary
      time, sedentary bouts, sedentary breaks, and BMI z-score among children and by
      low (bottom 50%) and high (top 50%) moderate- to vigorous-intensity physical
      activity (MVPA) participation. Results are based on 787 children aged 11 years
      living in Toronto, Canada. Children's physical activity and sedentary time were
      objectively assessed using ActiGraph accelerometers in 2010/11. Height and weight
      were measured and BMI z-scores were calculated based on the World Health
      Organization growth standards. When participants were stratified into low and
      high MVPA groups, sedentary bouts of 5-9 (beta = 0.22 [95% CI: 0.01, 0.43]) and
      10-19 (0.30 [-0.05, 0.55]) minutes for total days were associated with BMI z
      score in the low MVPA group only. Similar trends were observed with the weekday
      but not the weekend variables. Therefore, in addition to increasing MVPA,
      reducing time spent in 5- to 19-min sedentary bouts may have important
      implications for weight status particularly for children with lower MVPA
      participation during the week. 

PMID- 24092776
TI  - Whole-Genome Sequences of 94 Environmental Isolates of Bacillus cereus Sensu
      Lato.
AB  - Bacillus cereus sensu lato is a species complex that includes the anthrax
      pathogen Bacillus anthracis and other bacterial species of medical, industrial,
      and ecological importance. Their phenotypes of interest are typically linked to
      large plasmids that are closely related to the anthrax plasmids pXO1 and pXO2.
      Here, we present the draft genome sequences of 94 isolates of B. cereus sensu
      lato, which were chosen for their plasmid content and environmental origins. 

PMID- 24092775
TI  - A proangiogenic signature is revealed in FGF-mediated bevacizumab-resistant head
      and neck squamous cell carcinoma.
AB  - Resistance to antiangiogenic therapies is a critical problem that has limited the
      utility of antiangiogenic agents in clinical settings. However, the molecular
      mechanisms underlying this resistance have yet to be fully elucidated. In this
      study, we established a novel xenograft model of acquired resistance to
      bevacizumab. To identify molecular changes initiated by the tumor cells, we
      performed human-specific microarray analysis on bevacizumab-sensitive and 
      resistant tumors. Efficiency analysis identified 150 genes upregulated and 31
      genes downregulated in the resistant tumors. Among angiogenesis-related genes, we
      found upregulation of fibroblast growth factor-2 (FGF2) and fibroblast growth
      factor receptor-3 (FGFR3) in the resistant tumors. Inhibition of the FGFR in the
      resistant tumors led to the restoration of sensitivity to bevacizumab.
      Furthermore, increased FGF2 production in the resistant cells was found to be
      mediated by overexpression of upstream genes phospholipase C (PLCg2), frizzled
      receptor-4 (FZD4), chemokine [C-X3-C motif] (CX3CL1), and chemokine [C-C motif]
      ligand 5 (CCL5) via extracellular signal-regulated kinase (ERK). In summary, our
      work has identified an upregulation of a proangiogenic signature in bevacizumab
      refractory HNSCC tumors that converges on ERK signaling to upregulate FGF2, which
      then mediates evasion of anti-VEGF therapy. These findings provide a new strategy
      on how to enhance the therapeutic efficacy of antiangiogenic therapy.
      IMPLICATIONS: Novel xenograft model leads to the discovery of FGF as a promising
      therapeutic target in overcoming the resistance of antiangiogenic therapy in
      HNSCC.

PMID- 24092777
TI  - Complete Genome Sequence of Encapsulated Haemophilus influenzae Type f KR494, an
      Invasive Isolate That Caused Necrotizing Myositis.
AB  - Haemophilus influenzae serotype f (Hif) is an etiologic agent of bacterial
      invasive disease. Here, we report the first annotated genome sequence of the Hif
      strain KR494, which was isolated from a patient suffering from sepsis and
      necrotizing myositis. The genome sequence will increase the understanding of Hif
      pathogenesis. 

PMID- 24092778
TI  - Identification of a novel strain of human papillomavirus from children with
      diarrhea in china.
AB  - A highly divergent human papillomavirus (HPV) strain, HPV-L55, was identified in
      fecal samples from children hospitalized with diarrhea in China. The L1 gene of
      HPV-L55 shares <75% identity with previously reported HPVs, indicating that this
      virus represents a novel type of HPV. Phylogenetic analysis classified this virus
      as a member of the gammapapillomaviruses. 

PMID- 24092779
TI  - Genome Sequence of Marine Bacterium Idiomarina sp. Strain 28-8, Isolated from
      Korean Ark Shells.
AB  - Idiomarina sp. strain 28-8 is an aerobic, Gram-negative, flagellar bacterium
      isolated from the bodies of ark shells (Scapharca broughtonii) collected from
      underwater sediments in Gangjin Bay, South Korea. Here, we present the draft
      genome sequence of Idiomarina sp. 28-8 (2,971,606 bp, with a G+C content of
      46.9%), containing 2,795 putative coding sequences. 

PMID- 24092780
TI  - Genome Sequence of the Fructan-Degrading Organism Marinimicrobium sp. Strain LS
      A18, Isolated from a Marine Solar Saltern.
AB  - Marinimicrobium sp. strain LS-A18 is a fructan-degrading organism isolated from a
      brine sample from a marine solar saltern in Jiaozhou Bay, China. The draft genome
      sequence of this bacterium is 3,815,107 bp in length, with a G+C content of
      59.03%. To our knowledge, this is the first genome announcement of a fructan
      degrading strain of the genus Marinimicrobium. 

PMID- 24092781
TI  - Full-Genome Sequence of a Reassortant H1N1 Swine Influenza Virus Isolated from
      Pigs in Italy.
AB  - In this study, the full-genome sequence of a novel reassortant H1N1 swine
      influenza virus (SIV) is reported. The isolate has a hemagglutinin (HA) gene of
      the pandemic H1N1 influenza virus, but it carries the seven genome segments of
      the avian-origin H1N1 SIV currently circulating in European pig farms. 

PMID- 24092782
TI  - Genome Sequence of Streptococcus parauberis Strain KCTC11980, Isolated from
      Diseased Paralichthys olivaceus.
AB  - Streptococcus parauberis is a coccoid, nonmotile, alpha-hemolytic, Gram-positive
      bacterium of the Streptococcaceae family. Streptococcus parauberis strain
      KCTC11980 was isolated from the kidney of a diseased olive flounder collected
      from an aquaculture farm on Jeju Island in 2010. The 2.12-Mb genome sequence
      consists of 44 large contigs in 16 scaffolds and contains 2,214 predicted protein
      coding genes, with a G+C content of 35.4%. 

PMID- 24092783
TI  - Complete Genome Sequence of Reticuloendotheliosis Virus Strain MD-2, Isolated
      from a Contaminated Turkey Herpesvirus Vaccine.
AB  - Here, we present the complete genomic sequence of a reticuloendotheliosis virus
      (REV) isolated from a contaminated turkey herpesvirus (HVT) vaccine. This report
      will be helpful for epidemiological studies on REV infection in avian flocks. 

PMID- 24092784
TI  - Draft Genome Sequence of Vibrio coralliilyticus Strain OCN008, Isolated from
      Kane'ohe Bay, Hawai'i.
AB  - Vibrio coralliilyticus is a Gram-negative bacterium found in seawater and is
      associated with diseased marine organisms. Strains of V. coralliilyticus have
      been shown to infect coral from multiple genera. We report the draft genome
      sequence of V. coralliilyticus strain OCN008, the third V. coralliilyticus genome
      to be sequenced. 

PMID- 24092785
TI  - Bacillus cereus Sensu Lato Genomes: Basis for Identifying Anthrax Disease Strain
      Sources.

PMID- 24092786
TI  - Draft Genome Sequence of Aeromonas salmonicida subsp. achromogenes AS03, an
      Atypical Strain Isolated from Crucian Carp (Carassius carassius) in the Republic
      of Korea.
AB  - We present the draft genome sequence of Aeromonas salmonicida subsp. achromogenes
      strain AS03, an atypical A. salmonicida strain that causes erythrodermatitis in
      crucian carp (Carassius carassius). This is the first genome sequence report of
      A. salmonicida subsp. achromogenes, one of the four subspecies of atypical A.
      salmonicida. 

PMID- 24092787
TI  - Whole-Genome Sequence of the Clinical Strain Corynebacterium argentoratense DSM
      44202, Isolated from a Human Throat Specimen.
AB  - Corynebacterium argentoratense is part of the human skin microbiota and is
      occasionally detected in the upper respiratory tract of patients suffering from
      tonsillitis. The complete DNA sequence of the type strain DSM 44202 comprises
      2,031,902 bp, yielding the smallest genome sequenced thus far for a
      corynebacterium associated with humans. 

PMID- 24092788
TI  - Complete genome sequence of a new tobamovirus naturally infecting tomatoes in
      Mexico.
AB  - The complete genomic sequence of a new tobamovirus in tomatoes was determined
      through deep sequencing and assembly of small RNAs, then validated through Sanger
      sequencing. Based on the low sequence identity (<=85%) to known viruses and a
      close phylogenetic relationship to tobamoviruses, it was identified as a new
      species. 

PMID- 24092789
TI  - Draft Genome Sequence of a Neisseria meningitidis Serogroup C Isolate of Sequence
      Type 11 Linked to an Outbreak among Men Who Have Sex with Men.
AB  - Meningococcal disease occurs as sporadic cases in developed countries, with the
      occasional emergence of new clones of Neisseria meningitidis. Here, we report the
      genome sequence of N. meningitidis strain LNP27256, an isolate of sequence type
      11 linked to a recent outbreak among men who have sex with men in Europe. 

PMID- 24092790
TI  - Genome Sequence of the Quorum-Sensing-Signal-Producing Nonpathogen Agrobacterium
      tumefaciens Strain P4.
AB  - Agrobacterium tumefaciens P4 is a quorum-sensing-signal-producing bacterium that
      has been isolated from the tobacco rhizosphere. This strain belongs to
      genomospecies 1 of the A. tumefaciens complex; it is avirulent on various
      putative host plants, devoid of the Ti plasmid, and contains a luxI homolog on
      the At plasmid. 

PMID- 24092791
TI  - Draft Genome Sequence of Aeromonas veronii Hm21, a Symbiotic Isolate from the
      Medicinal Leech Digestive Tract.
AB  - Aeromonas veronii strain Hm21 was isolated from the digestive tract of the
      medicinal leech Hirudo verbana and has been used to identify genes that are
      important for host colonization. This species is also a symbiont in the gut of
      zebrafish and is a pathogen of mammals and fish. We present here a 4.68-Mbp draft
      genome sequence for Hm21. 

PMID- 24092792
TI  - Draft Genome Sequence of the Mycobacterium tuberculosis Strain 43-16836,
      Belonging to the Indo-Oceanic Lineage, Isolated From Tuberculous Meningitis in
      Thailand.
AB  - We present the draft genome sequence of Mycobacterium tuberculosis strain 43
      16836, belonging to the Indo-Oceanic lineage, isolated from a tuberculous
      meningitis patient in Thailand. The genome is 4,381,942 bp long with 4,316
      protein-coding genes and contains new single nucleotide polymorphisms (SNPs),
      including SNPs of genes that may encode cell wall components and possibly
      influence virulence. 

PMID- 24092793
TI  - Whole-genome sequences of five oyster-associated bacteria show potential for
      crude oil hydrocarbon degradation.
AB  - Draft genome sequences of oyster-associated Pseudomonas stutzeri strain MF28, P.
      alcaligenes strain OT69, P. aeruginosa strain WC55, Stenotrophomonas maltophilia
      strain MF89, and Microbacterium maritypicum strain MF109 are reported. Genome
      wide surveys of these isolates suggest that the oyster microbiome, which remains
      largely understudied, has a strong potential to degrade crude oil. 

PMID- 24092794
TI  - Draft Genome Sequence of Pasteurella multocida A:3 Strain 671/90.
AB  - Pasteurella multocida serogroup A is commonly isolated from nasal swabs of
      clinically healthy calves and also from diseased lung tissue in bovine pneumonia.
      Here, we report the draft genome sequence of the virulent strain P. multocida
      671/90, which has been characterized previously in experimental infections of
      calves and mice. 

PMID- 24092795
TI  - Draft Genome Sequences of Two O104:H21 Escherichia coli Isolates Causing
      Hemorrhagic Colitis during a 1994 Montana Outbreak Provide Insight into Their
      Pathogenicity.
AB  - We sequenced the genomes of two strains of O104:H21 enterohemorrhagic Escherichia
      coli (EHEC) isolated during an outbreak of hemorrhagic colitis in Montana in
      1994. These strains carried a plasmid that contains several virulence genes not
      present in pO157. The genome sequences will improve phylogenetic analysis of
      other non-O157 E. coli strains in the future. 

PMID- 24092796
TI  - Draft Genome Sequences of Two Salmonella Strains from the SARA Collection, SARA64
      (Muenchen) and SARA33 (Heidelberg), Provide Insight into Their Antibiotic
      Resistance.
AB  - The Salmonella enterica strains that are representatives of the S. enterica
      serovar Typhimurium complex in reference collection A (SARA) are closely related
      but exhibit differences in antibiotic resistance, which could have public health
      consequences. To better understand the mechanisms behind these resistances, we
      sequenced the genomes of two multidrug-resistant strains: SARA64 (Muenchen) and
      SARA33 (Heidelberg). 

PMID- 24092797
TI  - Insights from a chimpanzee adipose stromal cell population: opportunities for
      adult stem cells to expand primate functional genomics.
AB  - Comparisons between humans and chimpanzees are essential for understanding traits
      unique to each species. However, linking important phenotypic differences to
      underlying molecular changes is often challenging. The ability to generate,
      differentiate, and profile adult stem cells provides a powerful but underutilized
      opportunity to investigate the molecular basis for trait differences between
      species within specific cell types and in a controlled environment. Here, we
      characterize adipose stromal cells (ASCs) from Clint, the chimpanzee whose genome
      was first sequenced. Using imaging and RNA-Seq, we compare the chimpanzee ASCs
      with three comparable human cell lines. Consistent with previous studies on ASCs
      in humans, the chimpanzee cells have fibroblast-like morphology and express genes
      encoding components of the extracellular matrix at high levels. Differentially
      expressed genes are enriched for distinct functional classes between species:
      immunity and protein processing are higher in chimpanzees, whereas cell cycle and
      DNA processing are higher in humans. Although hesitant to draw definitive
      conclusions from these data given the limited sample size, we wish to stress the
      opportunities that adult stem cells offer for studying primate evolution. In
      particular, adult stem cells provide a powerful means to investigate the profound
      disease susceptibilities unique to humans and a promising tool for conservation
      efforts with nonhuman primates. By allowing for experimental perturbations in
      relevant cell types, adult stem cells promise to complement classic comparative
      primate genomics based on in vivo sampling. 

PMID- 24092798
TI  - Relationships between the importation, transmission, and nosocomial infections of
      methicillin-resistant Staphylococcus aureus: an observational study of 112
      Veterans Affairs Medical Centers.
AB  - BACKGROUND: The study of hospital methicillin-resistant Staphylococcus aureus
      (MRSA) epidemiology is complicated by its transmissibility. Our objective was to
      understand how MRSA importation and transmission influence MRSA nosocomial
      infections in Veterans Affairs Medical Centers (VAMCs). METHODS: We performed
      hospital-level analyses of acute-care MRSA admission prevalence, acquisition
      rates, and incident nosocomial clinical culture (INCC) rates, each a surrogate
      measure of importation, transmission, and nosocomial infection, respectively. We
      studied 112 VAMCs from October 2007 through September 2010, after the start of a
      bundled intervention including active surveillance for MRSA. We analyzed data
      using generalized linear mixed models. RESULTS: A total of 2.9 million
      surveillance tests were collected from 1.4 million patient admissions. Overall
      MRSA admission prevalence was 11.4%, acquisition was 5.2 per 1000 patient-days at
      risk, and INCC was 1.8 per 1000 patient-days at risk. A 10% increase in a
      hospital's average admission prevalence was associated with a 9.7% increase in
      its weekly acquisition rates (P < .001) and a 9.8% increase in its weekly INCC
      rates (P < .001). Significant decreases were observed in all 3 measures during
      the study period (P < .001). When INCC rates were stratified by nasal MRSA
      carriage at admission, a significant downward trend was observed only among those
      initially negative. CONCLUSIONS: Measured associations between MRSA admission
      prevalence, acquisition rate, and INCC rate were consistent with the hypothesis
      that decreased acquisition led to decreased importation, which in turn further
      abated acquisition. The downward trend in INCC rate specifically among
      individuals with negative admission surveillance tests suggests that decreasing
      transmission contributed to lower rates of nosocomial MRSA infection.

PMID- 24092800
TI  - Strokes and infection with varicella zoster virus.

PMID- 24092799
TI  - Priapism induced by boceprevir-CYP3A4 inhibition and alpha-adrenergic blockade:
      case report.
AB  - A 44-year-old white man presented to the emergency department with a 3-day
      history of priapism requiring a surgically performed distal penile shunt. A drug
      drug interaction is the suspected cause whereby CYP3A4 inhibition by boceprevir
      led to increased exposures of doxazosin, tamsulosin, and/or quetiapine, resulting
      in additional alpha-adrenergic blockade. 

PMID- 24092801
TI  - American society for apheresis guidelines support use of red cell exchange
      transfusion for severe malaria with high parasitemia.

PMID- 24092802
TI  - Chickenpox and risk of stroke: a self-controlled case series analysis.
AB  - BACKGROUND: There is good evidence that respiratory and other infections that
      cause systemic inflammation can trigger strokes; however, the role of specific
      infections is unclear. Case reports have highlighted chickenpox as a possible
      risk factor for arterial ischemic stroke, particularly in children, but rigorous
      studies are needed to determine and quantify any increased risk. METHODS: We used
      anonymized electronic health records totaling >100 million person-years of
      observation from 4 UK primary care databases to identify individuals who had
      documented clinical chickenpox and a stroke or transient ischemic attack (TIA).
      Self-controlled case series methods were used to quantify any increased risk of
      first stroke or TIA in the 0-6 and 7-12 months following chickenpox compared to
      other observed time periods. We analyzed data within each database, and performed
      meta-analyses to obtain summary age-adjusted incidence ratios (IRs) separately
      for adults and children. RESULTS: Five hundred sixty eligible individuals
      (including 60 children) were identified who experienced chickenpox and a stroke
      or TIA during follow-up. Among children, there was a 4-fold increased risk of
      stroke in the 0-6 months after chickenpox (summary IR = 4.07; 95% confidence
      interval [CI], 1.96-8.45; I(2) = 0%). Among adults, there was a less marked
      increased risk with moderate between-database heterogeneity (random-effects
      summary IR = 2.13; 95% CI, 1.05-4.36; I(2) = 51%). There was no significant
      increased risk of stroke in the 7-12 months after chickenpox in children or
      adults, nor was there evidence of increased risk of TIA in either time period.
      CONCLUSIONS: Our study provides new evidence that children who experience
      chickenpox are at increased risk of stroke in the subsequent 6 months.

PMID- 24092803
TI  - Reply to Shaz et al.

PMID- 24092804
TI  - Nondisclosure of HIV status in a clinical trial setting: antiretroviral drug
      screening can help distinguish between newly diagnosed and previously diagnosed
      HIV infection.
AB  - In The HIV Prevention Trials Network 061 study, 155 human immunodeficiency virus
      (HIV)-infected men reported no prior HIV diagnosis; 83 of those men had HIV RNA
      levels of <1000 copies/mL at enrollment. Antiretroviral drug testing revealed
      that 65 of the 83 (78.3%) men were on antiretroviral treatment. Antiretroviral
      drug testing can help distinguish between newly diagnosed and previously
      diagnosed HIV infection. 

PMID- 24092805
TI  - Bordetella holmesii bacteremia cases in the United States, April 2010-January
      2011.
AB  - We describe the first report of temporally related cases of Bordetella holmesii
      bacteremia. Demographic and clinical data were collected through chart
      abstraction and case-patient interviews. Twenty-two cases were identified from 6
      states. Symptom onset dates ranged from April 2010 to January 2011. Median age of
      patients was 17.1 years and 64% had functional or anatomic asplenia. Pulsed-field
      gel electrophoresis profiles of a sample of isolates were identical. These cases
      occurred during a peak in pertussis outbreaks with documented cases of B.
      holmesii/Bordetella pertussis respiratory coinfection; whether there is a link
      between B. holmesii respiratory and bloodstream infection is unknown. 

PMID- 24092806
TI  - Molecular and biologic analysis of histone deacetylase inhibitors with diverse
      specificities.
AB  - Histone deacetylase inhibitors (HDACi) are anticancer agents that induce
      hyperacetylation of histones, resulting in chromatin remodeling and
      transcriptional changes. In addition, nonhistone proteins, such as the chaperone
      protein Hsp90, are functionally regulated through hyperacetylation mediated by
      HDACis. Histone acetylation is thought to be primarily regulated by HDACs 1, 2,
      and 3, whereas the acetylation of Hsp90 has been proposed to be specifically
      regulated through HDAC6. We compared the molecular and biologic effects induced
      by an HDACi with broad HDAC specificity (vorinostat) with agents that
      predominantly inhibited selected class I HDACs (MRLB-223 and romidepsin). MRLB
      223, a potent inhibitor of HDACs 1 and 2, killed tumor cells using the same
      apoptotic pathways as the HDAC 1, 2, 3, 6, and 8 inhibitor vorinostat. However,
      vorinostat induced histone hyperacetylation and killed tumor cells more rapidly
      than MRLB-223 and had greater therapeutic efficacy in vivo. FDCP-1 cells
      dependent on the Hsp90 client protein Bcr-Abl for survival, were killed by all
      HDACis tested, concomitant with caspase-dependent degradation of Bcr-Abl. These
      studies provide evidence that inhibition of HDAC6 and degradation of Bcr-Abl
      following hyperacetylation of Hsp90 is likely not a major mechanism of action of
      HDACis as had been previously posited.

PMID- 24092807
TI  - BH3 profiling discriminates response to cytarabine-based treatment of acute
      myelogenous leukemia.
AB  - As acute myelogenous leukemia (AML) patient response to cytarabine-based standard
      of-care treatment is variable, stratification into subgroups by biomarker
      predicted response may lead to improved clinical outcomes. Here, we assess cell
      mitochondrial depolarization to proapoptotic signaling BH3-only peptides as a
      surrogate for the function of Bcl-2 family proteins to address clinical response
      to cytarabine-based therapy in patients with AML (N = 62). Peripheral blood
      mononuclear cell (PBMC) or bone marrow aspirate specimens were obtained from
      newly diagnosed patients with AML, viably preserved, and assayed by flow
      cytometry following BH3 profile assay with individual BH3 peptides. Mann-Whitney
      analysis indicates biomarker correlation with response to induction therapy:
      Notably, BIM priming was highly significant (P = 2 * 10(-6)) with a compelling
      sensitivity/specificity profile [area under curve (AUC) = 0.83; 95% confidence
      interval (CI), 0.73-0.94; P = 2 * 10(-10)]. Multivariate analysis indicates
      improved profiles for BIM readout + patient age (AUC = 0.89; 95% CI, 0.81-0.97)
      and BIM + patient age + cytogenetic status (AUC = 0.91; 95% CI, 0.83-0.98). When
      patients were stratified by cytogenetic status, BIM readout was significant for
      both intermediate (P = 0.0017; AUC = 0.88; 95% CI, 0.71-1.04) and unfavorable (P
      = 0.023; AUC = 0.79; 95% CI, 0.58-1.00) risk groups, demonstrating predictive
      power independent of cytogenetics. Additional analyses of secondary clinical
      endpoints displayed correlation between overall survival (P = 0.037) and event
      free survival (P = 0.044) when patients were stratified into tertiles by BIM
      peptide response. Taken together, these results highlight the potential utility
      of BH3 profiling in personalized diagnostics of AML by offering actionable
      information for patient management decisions.

PMID- 24092808
TI  - Treatment with gefitinib or lapatinib induces drug resistance through
      downregulation of topoisomerase IIalpha expression.
AB  - The EGF receptor (EGFR) is therapeutically targeted by antibodies and small
      molecules in solid tumors including lung, colorectal, and breast cancer. However,
      chemotherapy remains important, and efforts to improve efficacy through
      combination with targeted agents is challenging. This study examined the effects
      of short and long durations of exposure to the EGFR- and HER2-targeted tyrosine
      kinase inhibitors (TKI) gefitinib and lapatinib, on induction of cell death and
      DNA damage by topoisomerase IIalpha (Topo IIalpha) poisons, in the SK-Br-3 HER2
      amplified breast cancer cell line. Short exposure to either gefitinib or
      lapatinib for 1 hour did not affect the induction of apoptosis by the Topo
      IIalpha poisons doxorubicin, etoposide, and m-AMSA. In contrast, cells treated
      for 48 hours were resistant to all three drugs. Short exposure (1 hour) to TKI
      did not alter the number of DNA single- or double-strand breaks (DSB) induced,
      whereas longer exposure (48 hours) reduced the number of DNA DSBs and the
      formation of gamma-H2AX foci. Both gefitinib and lapatinib reduced the expression
      and activity of Topo IIalpha at 48 hours. Studies using a cell line with
      inducible downregulation of Topo IIalpha showed that expression of Topo IIalpha,
      and not Topo IIbeta, determined the number of DNA strand breaks induced by these
      chemotherapeutic agents. These results indicate that prolonged exposure to TKIs
      targeting EGFR and HER2 induce resistance to doxorubicin, etoposide, and m-AMSA
      through downregulation of Topo IIalpha. This may explain why their addition to
      chemotherapy regimens have not increased efficacy.

PMID- 24092809
TI  - Target-based therapeutic matching in early-phase clinical trials in patients with
      advanced colorectal cancer and PIK3CA mutations.
AB  - Target-matched treatment with PI3K/AKT/mTOR pathway inhibitors in patients with
      diverse advanced cancers with PIK3CA mutations have shown promise. Tumors from
      patients with colorectal cancer were analyzed for PIK3CA, KRAS, and BRAF
      mutations. PIK3CA-mutated tumors were treated, whenever feasible, with agents
      targeting the PI3K/AKT/mTOR pathway. Of 194 patients analyzed, 31 (16%) had
      PIK3CA mutations and 189 (97%) were assessed for KRAS mutations. Patients with
      PIK3CA mutations had a higher prevalence of simultaneous KRAS mutations than
      patients with wild-type PIK3CA (71%, 22/31 vs. 43%, 68/158; P = 0.006). Of 31
      patients with PIK3CA mutations, 17 (55%) were treated with protocols containing
      PI3K/AKT/mTOR pathway inhibitors [median age, 57 years; median number of prior
      therapies, 4; mTORC1 inhibitors (11), phosphoinositide 3-kinase (PI3K) inhibitors
      (5), or an AKT inhibitor (1)]. None (0/17) had a partial or complete response
      (PR/CR) and only 1 [6%, 95% confidence interval (CI), 0.01-0.27] had stable
      disease 6 months or more, which was not significantly different from a stable
      disease >=6 month/PR/CR rate of 16% (11/67; 95% CI, 0.09-0.27) in patients with
      colorectal cancer without PIK3CA mutations treated with PI3K/AKT/mTOR pathway
      inhibitors (P = 0.44). Median progression-free survival was 1.9 months (95% CI,
      1.5-2.3). In conclusion, our data provide preliminary evidence that in heavily
      pretreated patients with PIK3CA-mutant advanced colorectal cancer, protocols
      incorporating PI3K/AKT/mTOR inhibitors have minimal activity. PIK3CA mutations
      are associated with simultaneous KRAS mutations, possibly accounting for
      therapeutic resistance.

PMID- 24092810
TI  - HDAC inhibitor entinostat restores responsiveness of letrozole-resistant MCF-7Ca
      xenografts to aromatase inhibitors through modulation of Her-2.
AB  - We previously showed that in innately resistant tumors, silencing of the estrogen
      receptor (ER) could be reversed by treatment with a histone deacetylase (HDAC)
      inhibitor, entinostat. Tumors were then responsive to aromatase inhibitor (AI)
      letrozole. Here, we investigated whether ER in the acquired letrozole-resistant
      tumors could be restored with entinostat. Ovariectomized athymic mice were
      inoculated with MCF-7Ca cells, supplemented with androstenedione (Delta(4)A), the
      aromatizable substrate. When the tumors reached about 300 mm(3), the mice were
      treated with letrozole. After initial response to letrozole, the tumors
      eventually became resistant (doubled their initial volume). The mice then were
      grouped to receive letrozole, exemestane (250 MUg/d), entinostat (50 MUg/d), or
      the combination of entinostat with letrozole or exemestane for 26 weeks. The
      growth rates of tumors of mice treated with the combination of entinostat with
      letrozole or exemestane were significantly slower than with the single agent (P <
      0.05). Analysis of the letrozole-resistant tumors showed entinostat increased
      ERalpha expression and aromatase activity but downregulated Her-2, p-Her-2, p
      MAPK, and p-Akt. However, the mechanism of action of entinostat in reversing
      acquired resistance did not involve epigenetic silencing but rather included
      posttranslational as well as transcriptional modulation of Her-2. Entinostat
      treatment reduced the association of the Her-2 protein with HSP-90, possibly by
      reducing the stability of Her-2 protein. In addition, entinostat also reduced Her
      2 mRNA levels and its stability. Our results suggest that the HDAC inhibitor may
      reverse letrozole resistance in cells and tumors by modulating Her-2 expression
      and activity.

PMID- 24092811
TI  - Tetravalent antibody-scTRAIL fusion proteins with improved properties.
AB  - We applied the immunoglobulin E (IgE) heavy-chain domain 2 (EHD2) as the
      covalently linked homodimerization module to generate antibody-scTRAIL fusion
      proteins. By fusing a humanized single-chain fragment variable (scFv) directed
      against EGFR to the N-terminus of the EHD2 and a single-chain derivative of TRAIL
      (scTRAIL) to the C-terminus of the EHD2, we produced a dimeric, tetravalent
      fusion protein. The fusion protein retained its binding activity for EGFR and
      TRAIL receptors. In vitro, the targeted antibody-scTRAIL fusion protein exhibited
      an approximately 8- to 18-fold increased cytotoxic activity compared with the
      untargeted EHD2-scTRAIL fusion protein. This resulted in increased antitumor
      activity in a subcutaneous Colo205 xenograft tumor murine model. In summary, the
      scFv-EHD2-scTRAIL fusion protein combines target cell selectivity with an
      increased TRAIL activity leading to improved antitumor activities.

PMID- 24092812
TI  - The global tobacco epidemic: public health crisis and public health opportunity.

PMID- 24092814
TI  - Tobacco consumption: the Asia-Pacific Region's major public health problem.

PMID- 24092813
TI  - Maternal use of cigarettes, pipes, and smokeless tobacco associated with higher
      infant mortality rates in Cambodia.
AB  - In the Western Pacific Region, rural women use loose tobacco in betel quid
      chewing and pipe smoking. We examined the relation between maternal use of
      tobacco and infant mortality (IM) in a national sample of 24 296 birth outcomes
      in adult women (n = 6013) in Cambodia. We found that (1) age-adjusted odds of IM
      were higher for maternal use of any tobacco (odds ratio [OR] = 1.69; 95%
      confidence interval [CI] = 1.27-2.26); (2) age-adjusted odds of IM were higher
      for cigarette use (OR = 2.54; 95% CI = 1.54- 4.1), use of pipes (OR = 3.09; [95%
      CI = 1.86-5.11]), and betel quid chewing (OR = 1.55; 95% CI = 1.10-2.17); and (3)
      these associations remained after multivariable adjustment for environmental
      tobacco smoke, malnutrition, ethnicity, religion, marital status, education,
      income, occupation, and urban/rural dwelling. In addition to finding the
      established association with cigarettes, we also found that maternal use of
      smokeless tobacco and pipes was associated with higher rates of infant death in
      Cambodia. 

PMID- 24092815
TI  - Cotinine levels among betel quid users and cigarette smokers in Cambodia.
AB  - Smokeless tobacco use in the form of the betel quid is common in the Western
      Pacific Region, and yet few studies have determined the nicotine delivery of this
      habit. During a validation substudy, we randomly sampled 201 adults from a rural
      province of Cambodia and determined nonparametric (bootstrapped) confidence
      intervals (CIs) for salivary cotinine levels in tobacco users. We found that
      cotinine levels for daily betel quid use among women (95% CI = 218.6-350.0 ng/mL)
      were (1) similar to the levels for daily cigarette smoking in men (95% CI = 240.2
      317.1 ng/mL) and (2) significantly higher than the levels for daily cigarette
      smoking in women (95% CI = 71.8-202.7 ng/mL). The 95% confidence range for these
      habits exceeded the threshold for addiction. Our findings from rural Cambodia
      indicate that the typical betel quid habit among women supports the same level of
      nicotine addiction as the typical cigarette habit in men. 

PMID- 24092816
TI  - Plasminogen activator inhibitor-1: a novel therapeutic target for hypertension?

PMID- 24092817
TI  - Plasminogen activator inhibitor-1 antagonist TM5441 attenuates Nomega-nitro-L
      arginine methyl ester-induced hypertension and vascular senescence.
AB  - BACKGROUND: Long-term inhibition of nitric oxide synthase by L-arginine analogues
      such as N(omega)-nitro-l-arginine methyl ester (L-NAME) has been shown to induce
      senescence in vitro and systemic hypertension and arteriosclerosis in vivo. We
      previously reported that plasminogen activator inhibitor-1 (PAI-1)-deficient mice
      (PAI-1(-/-)) are protected against L-NAME-induced pathologies. In this study, we
      investigated whether a novel, orally active PAI-1 antagonist (TM5441) has a
      similar protective effect against L-NAME treatment. Additionally, we studied
      whether L-NAME can induce vascular senescence in vivo and investigated the role
      of PAI-1 in this process. METHODS AND RESULTS: Wild-type mice received either L
      NAME or L-NAME and TM5441 for 8 weeks. Systolic blood pressure was measured every
      2 weeks. We found that TM5441 attenuated the development of hypertension and
      cardiac hypertrophy compared with animals that had received L-NAME alone.
      Additionally, TM5441-treated mice had a 34% reduction in periaortic fibrosis
      relative to animals on L-NAME alone. Finally, we investigated the development of
      vascular senescence by measuring p16(Ink4a) expression and telomere length in
      aortic tissue. We found that L-NAME increased p16(Ink4a) expression levels and
      decreased telomere length, both of which were prevented with TM5441 cotreatment.
      CONCLUSIONS: Pharmacological inhibition of PAI-1 is protective against the
      development of hypertension, cardiac hypertrophy, and periaortic fibrosis in mice
      treated with L-NAME. Furthermore, PAI-1 inhibition attenuates the arterial
      expression of p16(Ink4a) and maintains telomere length. PAI-1 appears to play a
      pivotal role in vascular senescence, and these findings suggest that PAI-1
      antagonists may provide a novel approach in preventing vascular aging and
      hypertension.

PMID- 24092818
TI  - Epoxyeicosatrienoic acids prevent cisplatin-induced renal apoptosis through a p38
      mitogen-activated protein kinase-regulated mitochondrial pathway.
AB  - Soluble epoxide hydrolase (sEH) catalyzes the conversion of epoxyeicosatrienoic
      acids into less active eicosanoids, and inhibitors of sEH have anti-inflammatory
      and antiapoptotic properties. Based on previous observations that sEH inhibition
      attenuates cisplatin-induced nephrotoxicity by modulating nuclear factor-kappaB
      signaling, we hypothesized that this strategy would also attenuate cisplatin
      induced renal apoptosis. Inhibition of sEH with AR9273 [1-adamantan-1-yl-3-(1
      methylsulfonyl-piperidin-4-yl-urea)] reduced cisplatin-induced apoptosis through
      mechanisms involving mitochondrial apoptotic pathways and by reducing reactive
      oxygen species. Renal mitochondrial Bax induction following cisplatin treatment
      was significantly decreased by treatment of mice with AR9273 and these
      antiapoptotic effects involved p38 mitogen-activated protein kinase signaling.
      Similar mechanisms contributed to reduced apoptosis in Ephx2(-/-) mice treated
      with cisplatin. Moreover, in pig kidney proximal tubule cells, cisplatin-induced
      mitochondrial trafficking of Bax and cytochrome c, caspase-3 activation, and
      oxidative stress are significantly attenuated in the presence of
      epoxyeicosatrienoic acids (EETs). Collectively, these in vivo and in vitro
      studies demonstrate a role for EETs in limiting cisplatin-induced renal
      apoptosis. Inhibition of sEH represents a novel therapeutic strategy for
      protection against cisplatin-induced renal damage. 

PMID- 24092819
TI  - Point and click, carefully: investigating inconsistent response styles in middle
      school and college students involved in web-based longitudinal substance use
      research.
AB  - This study investigated inconsistent responding to survey items by participants
      involved in longitudinal, web-based substance use research. We also examined
      cross-sectional and prospective predictors of inconsistent responding. Middle
      school (N = 1,023) and college students (N = 995) from multiple sites in the
      United States responded to online surveys assessing substance use and related
      variables in three waves of data collection. We applied a procedure for creating
      an index of inconsistent responding at each wave that involved identifying pairs
      of items with considerable redundancy and calculating discrepancies in responses
      to these items. Inconsistent responding was generally low in the Middle School
      sample and moderate in the College sample, with individuals showing only modest
      stability in inconsistent responding over time. Multiple regression analyses
      identified several baseline variables-including demographic, personality, and
      behavioral variables-that were uniquely associated with inconsistent responding
      both cross-sectionally and prospectively. Alcohol and substance involvement
      showed some bivariate associations with inconsistent responding, but these
      associations largely were accounted for by other factors. The results suggest
      that high levels of carelessness or inconsistency do not appear to characterize
      participants' responses to longitudinal web-based surveys of substance use and
      support the use of inconsistency indices as a tool for identifying potentially
      problematic responders.

PMID- 24092820
TI  - Characterizing the genetic basis of transcriptome diversity through RNA
      sequencing of 922 individuals.
AB  - Understanding the consequences of regulatory variation in the human genome
      remains a major challenge, with important implications for understanding gene
      regulation and interpreting the many disease-risk variants that fall outside of
      protein-coding regions. Here, we provide a direct window into the regulatory
      consequences of genetic variation by sequencing RNA from 922 genotyped
      individuals. We present a comprehensive description of the distribution of
      regulatory variation--by the specific expression phenotypes altered, the
      properties of affected genes, and the genomic characteristics of regulatory
      variants. We detect variants influencing expression of over ten thousand genes,
      and through the enhanced resolution offered by RNA-sequencing, for the first time
      we identify thousands of variants associated with specific phenotypes including
      splicing and allelic expression. Evaluating the effects of both long-range intra
      chromosomal and trans (cross-chromosomal) regulation, we observe modularity in
      the regulatory network, with three-dimensional chromosomal configuration playing
      a particular role in regulatory modules within each chromosome. We also observe a
      significant depletion of regulatory variants affecting central and critical
      genes, along with a trend of reduced effect sizes as variant frequency increases,
      providing evidence that purifying selection and buffering have limited the
      deleterious impact of regulatory variation on the cell. Further, generalizing
      beyond observed variants, we have analyzed the genomic properties of variants
      associated with expression and splicing and developed a Bayesian model to predict
      regulatory consequences of genetic variants, applicable to the interpretation of
      individual genomes and disease studies. Together, these results represent a
      critical step toward characterizing the complete landscape of human regulatory
      variation.

PMID- 24092821
TI  - Bacteria-derived DNA fragment in peritoneal dialysis effluent as a predictor of
      relapsing peritonitis.
AB  - BACKGROUND AND OBJECTIVES: Relapsing and recurrent peritonitis episodes are
      important causes of treatment failure in patients undergoing peritoneal dialysis
      (PD). This study explored whether the level of bacteria-derived DNA fragment in
      PD effluent predicts the development of relapsing or recurrent peritonitis.
      DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: The study included 143 patients
      with PD peritonitis in a dialysis unit between September 2010 and December 2011.
      Every 5 days until antibiotic treatment ended, PD effluent was collected to
      determine bacteria-derived DNA fragment level, which is represented by the number
      of PCR cycles at which bacterial DNA could be detected. Patients were followed
      for the development of relapsing or recurrent peritonitis. RESULTS: Thirty-nine
      patients were excluded because of immediate treatment failure or incorrect
      diagnosis. Of the other 104 patients, 15 (14.4%) developed relapsing peritonitis,
      3 (2.9%) had recurrent peritonitis, and 5 (4.8%) had repeat episodes. Patients
      with relapsing or recurrent peritonitis episodes had significantly higher levels
      of bacterial DNA fragment in PD effluent than those without relapsing or
      recurrence, both 5 days before (31.9 +/- 3.4 versus 34.3 +/- 3.0 cycles; P=0.002)
      and on the day of (32.3 +/- 2.6 versus 34.1 +/- 1.7 cycles; P<0.001) completion
      of antibiotics. When bacterial DNA fragment detectable by 34 PCR cycles 5 days
      before the completion of antibiotics is used as the cutoff, it has a sensitivity
      of 88.9% and specificity of 60.5% for the prediction of relapsing or recurrent
      peritonitis. CONCLUSIONS: Bacterial DNA fragment levels in PD effluent are
      significantly higher, both 5 days before and on the date of completion of
      antibiotics, among patients who subsequently develop relapsing or recurrent
      peritonitis than among those cured by antibiotics. Further studies are needed to
      validate these results and confirm the clinical utility of dialysate bacterial
      DNA fragment level.

PMID- 24092822
TI  - Optimizing function and physical activity among nursing home residents with
      dementia: testing the impact of function-focused care.
AB  - PURPOSE OF THE STUDY: The purpose of this study was to test the impact of
      Function-Focused Care for the Cognitively Impaired Intervention on nursing home
      residents with dementia and the nursing assistants who care for them. DESIGN AND
      METHODS: This was a cluster-randomized controlled trial using repeated measures.
      A total of 103 cognitively impaired residents and 77 nursing assistants were
      recruited from four nursing homes. For residents, outcome measures included
      function, physical activity (survey and actigraphy), mood, behavior, and adverse
      events (falls and hospitalization). Main outcome measures for nursing assistants
      included knowledge, beliefs, and performance of function focused care. RESULTS:
      There were significant improvements in the amount and intensity of physical
      activity (by survey and actigraphy) and physical function in the treatment group.
      In addition, there was a significant decrease in the number of residents who fell
      during the treatment period with those in the treatment sites having fewer falls
      (28% vs. 50% in the control group). Nursing assistants were also observed to be
      providing a greater percentage of function focused care during resident care
      interactions in the treatment group at 6 months following the completion of
      baseline measures. IMPLICATIONS: This study provides some evidence that nursing
      home residents with severe cognitive impairment can safely and successfully be
      engaged in physical and functional activities.

PMID- 24092823
TI  - Expression of SSTR2a, but not of SSTRs 1, 3, or 5 in somatotroph adenomas
      assessed by monoclonal antibodies was reduced by octreotide and correlated with
      the acute and long-term effects of octreotide.
AB  - CONTEXT: Reduced expression of somatostatin receptors (SSTRs) in somatotroph
      adenomas and their potential down-regulation after medical treatment may explain
      the unsatisfactory response to octreotide in particular acromegalic patients. The
      expression of SSTRs other than SSTR2a has not been studied in large, unselected
      cohorts using novel rabbit monoclonal antibodies. OBJECTIVE: We aimed to
      determine the expression of SSTRs 1, 2a, 3, and 5 in somatotroph adenomas, to
      correlate expression with clinical characteristics and the response to
      octreotide, and to ascertain whether preoperative octreotide treatment affected
      SSTR expression. DESIGN, SETTING, PATIENTS: The study included 78 adenomas from
      patients operated on consecutively during 2000 to 2010. After exclusion of 13
      patients, immunohistochemical analysis with rabbit monoclonal antibodies against
      SSTRs 1, 2a, 3, and 5 (clones UMB-7, -1, -5, and -4) was performed on 65
      adenomas. INTERVENTION: Twenty-eight patients received preoperative octreotide,
      and 37 patients were operated on without pretreatment. Twenty-six patients were
      randomized to direct surgery (n = 13) or to octreotide pretreatment (n = 13).
      MAIN OUTCOME MEASURE: SSTR expression was evaluated using a 12-grade scoring
      system. The responses to the octreotide test dose (GH reduction) and to 6 months
      of octreotide (IGF-I reduction) were measured. RESULTS: The majority of adenomas
      showed membranous expression of SSTRs 2a and 5. SSTR2a expression was reduced in
      the pretreated group and correlated with the acute octreotide test results and
      the effect of octreotide treatment. In a linear regression model with SSTR2a
      expression as the determinant, the correlation with the acute test response
      improved after adjustment for medical pretreatment. CONCLUSION: Rabbit monoclonal
      antibodies are reliable markers of SSTRs in somatotroph adenomas. SSTR2a
      expression correlated with the response to octreotide and was reduced after
      octreotide treatment, indicating the need for adjustment when SSTR2a expression
      is correlated with baseline characteristics. Evaluation of SSTR subtypes may be
      an important aspect of improving the medical treatment for acromegaly.

PMID- 24092824
TI  - EGF-like growth factors induce COX-2-derived PGE2 production through ERK1/2 in
      human granulosa cells.
AB  - CONTEXT: Aberrant regulation of ovulation is one of the major causes of
      infertility. In animal models, 3 epidermal growth factor (EGF)-like growth
      factors, amphiregulin (AREG), betacellulin (BTC), and epiregulin (EREG), have
      been shown to be involved in ovulation by regulating cyclooxygenase-2 (COX-2)
      expression and prostaglandin E2 (PGE2) production. However, whether the same is
      true in humans remains largely unknown. OBJECTIVE: Our objective was to
      investigate the effects of AREG, BTC, and EREG on COX-2 expression and PGE2
      production in human granulosa cells. DESIGN AND SETTING: SVOG cells are human
      granulosa cells that were obtained from women undergoing in vitro fertilization
      and immortalized with SV40 large T antigen. SVOG cells were used to investigate
      the effect of AREG, BTC, and EREG on ovulation-related functions at an academic
      research center. MAIN OUTCOME MEASURES: Levels of mRNA and protein were examined
      by quantitative RT-PCR and Western blotting, respectively. The protein levels of
      PGE2 were measured by ELISA. RESULTS: LH treatment upregulated AREG, BTC, EREG,
      and COX-2. Knockdown of EGF receptor (EGFR) attenuated LH-induced COX-2
      expression and PGE2 production. Treatment with AREG, BTC, and EREG upregulated
      COX-2 expression and PGE2 production. The stimulatory effects of AREG, BTC, and
      EREG on COX-2 expression and PGE2 production were blocked by inhibition of EGFR
      activity and expression. AREG-, BTC-, and EREG-activated ERK1/2 signaling, but
      not Akt signaling, was required for AREG-, BTC-, and EREG-induced COX-2
      expression and PGE2 production. CONCLUSION: AREG, BTC, and EREG induced PGE2
      production by upregulating COX-2 expression through ERK1/2 signaling in human
      granulosa cells.

PMID- 24092825
TI  - Influence of estrogen therapy on calcium, phosphorus, and other regulatory
      hormones in postmenopausal women: the MESA study.
AB  - BACKGROUND: Estrogen therapy (ET) is associated with lower serum calcium and
      phosphorus concentrations and is known to increase bone mineral density (BMD).
      Other biomarkers of mineral metabolism may help understand the biological basis
      of these actions. METHODS: We studied 2767 postmenopausal women in the Multi
      Ethnic Study of Atherosclerosis, 862 (31%) of whom were using ET. We measured
      serum concentrations of calcium, phosphorus, 25-hydroxyvitamin D, 24,25
      dihydoxyvitamin D, and fibroblast growth factor-23 and urinary fractional
      excretion of calcium (FEca) and phosphorus (FEphos). We examined the associations
      of ET with each biomarker. In addition, we tested whether the adjustment for
      biomarkers attenuated the association of ET with lumbar BMD measured by abdominal
      computed tomography in a subset of 810 women. RESULTS: In adjusted models, women
      who used ET were younger in age [62 (SD 8) vs 66 (9) y, P < .001], had lower mean
      serum calcium [-13 mg/dL (95% confidence interval [CI] -0.17, -0.10), P < .001]
      and lower FEca [-0.15% (95% CI -0.21, -0.09), P < .001]. Mean serum phosphorus
      was lower [-0.19 mg/dL (95% CI -0.23, -0.15), P < .001] and FEphos [0.56% (95% CI
      0.16, 0.96), P = .007] was higher in women on ET. Mean 25-hydroxyvitamin D and
      24,25-dihydroxyvitamin D were higher [1.52 ng/dL (95% CI 0.57, 2.47), P = .002,
      and 0.26 ng/mL (95% CI 0.03, 0.48), P = .03, respectively] in women who used ET.
      Mean PTH and fibroblast growth factor-23 did not differ significantly by the use
      of ET. ET use was strongly associated with higher lumbar BMD [12.75 mg/cm3 (95%
      CI 7.77-17.73), P < .001]; however, mineral metabolism measures did not
      meaningfully alter this association. CONCLUSIONS: In a multiethnic cohort of
      postmenopausal women, ET use was associated with lower serum calcium, lower FEca,
      lower serum phosphorus, and higher FEphos, suggesting these associations are
      attributable to increased calcium intake into bone and increased urinary
      phosphorus excretion. ET use was also associated with greater concentrations of
      vitamin D metabolites. ET-associated differences in these mineral metabolism
      measures did not meaningfully attenuate the strong association between ET use and
      lumbar BMD.

PMID- 24092826
TI  - Improved glycemic control enhances the incretin effect in patients with type 2
      diabetes.
AB  - BACKGROUND AND AIMS: Impairment of the incretin effect is one of the hallmarks of
      type 2 diabetes mellitus (T2DM). However, it is unknown whether this abnormality
      is specific to incretin-stimulated insulin secretion or a manifestation of
      generalized beta-cell dysfunction. The aim of this study was to determine whether
      improved glycemic control restores the incretin effect. METHODS: Fifteen T2DM
      subjects were studied before and after 8 weeks of intensified treatment with
      insulin. The incretin effect was determined by comparing plasma insulin and C
      peptide levels at clamped hyperglycemia from iv glucose, and iv glucose plus
      glucose ingestion. RESULTS: Long-acting insulin, titrated to reduce fasting
      glucose to 7 mM, lowered hemoglobin A1c from 8.6% +/- 0.2% to 7.1% +/- 0.2% over
      8 weeks. The incremental C-peptide responses and insulin secretion rates to iv
      glucose did not differ before and after insulin treatment (5.6 +/- 1.0 and 6.0 +/
      0.9 nmol/L.min and 0.75 +/- 0.10 and 0.76 +/- 0.11 pmol/min), but the C-peptide
      response to glucose ingestion was greater after treatment than before (10.9 +/-
      2.2 and 7.1 +/- 0.9 nmol/L.min; P = .03) as were the insulin secretion rates
      (1.11 +/- 0.22 and 0.67 +/- 0.07 pmol/min; P = .04). The incretin effect computed
      from plasma C-peptide was 21.8% +/- 6.5% before insulin treatment and increased
      40.9% +/- 3.9% after insulin treatment (P < .02). CONCLUSION: Intensified insulin
      treatment to improve glycemic control led to a disproportionate improvement of
      insulin secretion in response to oral compared with iv glucose stimulation in
      patients with type 2 diabetes. This suggests that in T2DM the impaired incretin
      effect is independent of abnormal glucose-stimulated insulin secretion.

PMID- 24092828
TI  - A cryptic cause of Cushing's disease.

PMID- 24092827
TI  - Essential role of estrogen for improvements in vascular endothelial function with
      endurance exercise in postmenopausal women.
AB  - OBJECTIVE: In contrast to age-matched men, endurance exercise training is not
      consistently associated with enhanced endothelial function in estrogen-deficient
      postmenopausal women. We determined whether endurance exercise training improves
      endothelial function in postmenopausal women treated with estrogen. In a
      substudy, we determined if oxidative stress is mechanistically linked to
      endothelial function adaptations to endurance exercise training. PARTICIPANTS AND
      DESIGN: Brachial artery flow-mediated dilation (FMD) was measured in 36
      sedentary, estrogen-deficient postmenopausal women (45-65 y) at study entry
      (baseline), after 12 weeks of either placebo, oral (1 mg/d) estradiol, or
      transdermal estradiol (0.05 mg/d) (randomized), and after an additional 12 weeks
      of continued estradiol or placebo treatment with concurrent endurance exercise
      training. In subgroups of women, FMD also was measured during the infusion of
      ascorbic acid at baseline and following estradiol/placebo plus endurance exercise
      training, and in seven habitually endurance-trained estrogen-deficient controls.
      RESULTS: FMD increased in the estrogen-treated groups (both P < .01) after 12
      weeks and remained unchanged in placebo. FMD further increased following 12 weeks
      of endurance exercise training in estrogen-treated (both P < .025), but not
      placebo-treated women (P = .55). In the substudy, baseline FMD was similar
      between sedentary and endurance-trained controls. Ascorbic acid increased FMD at
      baseline in sedentary women and endurance-trained controls, and following
      endurance exercise training in placebo-treated, but not in estrogen-treated
      women. CONCLUSIONS: Estrogen status appears to play an important modulatory role
      in improvements in endothelial function with endurance exercise training in
      postmenopausal women. The restored endurance exercise training adaptation in
      estrogen-treated postmenopausal women may be related to mitigation of oxidative
      stress.

PMID- 24092829
TI  - Diabetes modifies effect of high-phosphate diet on fibroblast growth factor-23 in
      chronic kidney disease.
AB  - CONTEXT: The pathophysiology of calcium-phosphate disturbances in diabetic (DM)
      kidney disease differs from that in non-DM chronic kidney disease (CKD).
      OBJECTIVE: We compared the effect of a 6-day high-phosphate diet on serum
      fibroblast growth factor-23 (FGF-23) and other parameters of calcium-phosphate
      metabolism in DM and non-DM CKD patients. DESIGN AND SETTING: This was a
      prospective interventional study in a research center setting. PARTICIPANTS,
      INTERVENTION, AND MEASURES: Twenty-six nondialysis patients with stages 3-5 CKD
      and albuminuria less than 300 mg/g creatinine were recruited from February 2011
      to November 2012 (15 DM, 11 non-DM). All patients received a high-phosphate diet
      (1800 mg/d) for 6 days. At baseline, day 3, and day 7 serum FGF-23, PTH, Ca, P,
      25-hydroxyvitamin D, 1,25 dihydroxyvitamin D, monocyte chemoattractant protein-1,
      and calcium and phosphate urine excretion were measured. RESULTS: In DM CKD
      patients, serum calcium was lower on days 3 and 7 vs baseline (P < .01,
      respectively), and in non-DM patients, it was unchanged. Serum phosphorus
      increased significantly only in non-DM patients on days 3 and 7 vs baseline (P <
      0.01, respectively). Serum PTH was higher in the DM group on day 7 vs baseline (P
      = .04). Plasma 25-hydroxyvitamin D, 1,25 dihydroxyvitamin D, and serum monocyte
      chemoattractant protein-1 were unchanged in both groups. Serum FGF-23 increased
      in DM patients, from baseline to day 3 (58.1 +/- 52.7 and 91.6 +/- 71.1 pg/mL, P
      = .001) but later tended to decrease. In non-DM patients, there was a steady
      increase of FGF-23 between baseline and day 7 (75 +/- 84.3 to 176 +/- 197 pg/mL,
      P = .04). Urine phosphate excretion was significantly higher on day 7 in DM
      patients only (P < .05). CONCLUSIONS: PTH seems to play the major role in the
      regulation of phosphate excretion in DM CKD. The role of FGF-23 in phosphate
      disposal in DM CKD remains debatable.

PMID- 24092831
TI  - The severity of menstrual dysfunction as a predictor of insulin resistance in
      PCOS.
AB  - OBJECTIVE: The objective of the study was to evaluate the relationship between
      the severity of menstrual disturbances and the degree of insulin resistance in
      women with polycystic ovary syndrome (PCOS). DESIGN: This was a cross-sectional
      study. SETTING: The study was conducted at a tertiary care academic medical
      center. PATIENTS: Four hundred ninety-four women diagnosed with PCOS by the
      Rotterdam criteria and 138 eumenorrheic, nonhirsute, control women participated
      in the study. INTERVENTIONS: INTERVENTIONS in the study included history and
      physical examination and blood sampling. MAIN OUTCOME MEASURE(S): Physical
      assessment and total and free T, dehydroepiandrosterone sulfate, fasting glucose,
      and insulin levels and calculated homeostatic model assessment values for insulin
      resistance (HOMA-IR) were measured. RESULTS: Overall, 80% of PCOS subjects
      included had clinically evident oligomenorrhea. The remainder demonstrated
      vaginal bleeding intervals of fewer than 35 days (ie, with either polymenorrhea
      or clinically apparent eumenorrhea). Only 10% of PCOS subjects studied were
      ovulatory. After adjusting for body mass index, age, and race, all PCOS subjects
      with menstrual cycles longer than 35 days had significantly higher mean HOMA-IR
      levels than controls, and those with cycles longer than 3 months had the highest
      HOMA-IR levels. There was no difference in mean HOMA-IR levels between PCOS with
      regular vaginal bleeding (apparent eumenorrhea), regardless of whether they were
      anovulatory or not, or those with cycles fewer than 26 days, when compared with
      controls. CONCLUSIONS: Women with PCOS and overt oligomenorrhea comprise the vast
      majority of PCOS subjects seen clinically and have significantly more insulin
      resistance than controls. About 20% of PCOS women seen reported vaginal bleeding
      intervals of fewer than 35 days in length and did not generally have overt
      insulin resistance, regardless of whether they were ovulatory or not. Overall,
      the presence of clinically evident menstrual dysfunction can be used to predict
      the presence and possibly the degree of insulin resistance in women with PCOS.

PMID- 24092830
TI  - Adverse effects of the common treatments for polycystic ovary syndrome: a
      systematic review and meta-analysis.
AB  - CONTEXT: Polycystic ovary syndrome (PCOS) is common among women of childbearing
      age and the available pharmacological therapies have different side-effect
      profiles. OBJECTIVE: We summarized the evidence about the side effects of oral
      contraceptive pills, metformin, and anti-androgens in women with PCOS. DATA
      SOURCE: Sources included Ovid Medline, OVID EMBASE, OVID Cochrane Library, Web of
      Science, Scopus, PsycInfo, and CINAHL from inception through April 2011. STUDY
      SELECTION: We included comparative observational studies enrolling women with
      PCOS who received the agents of choice for at least 6 months and reported adverse
      effects. DATA EXTRACTION: Using a standardized, piloted, and Web-based data
      extraction form and working in duplicate, we abstracted data from each study and
      performed meta-analysis when possible. DATA SYNTHESIS: We found 22 eligible
      studies of which 20 were randomized. No study reported severe side effects (eg,
      lactic acidosis, thromboembolic episodes, liver toxicity, cancer incidence, or
      pregnancy loss). Meta-analysis demonstrated no significant change in weight in
      oral contraceptive pills or flutamide users. Indirect evidence from populations
      without PCOS demonstrated no increased risk of lactic acidosis with metformin,
      only case reports of liver toxicity with flutamide (no comparative evidence), and
      increased relative risk difference of venous thromboembolism with oral
      contraceptive pills but very low absolute risk. Evidence on mortality,
      cardiovascular mortality, and cancer was inconclusive. CONCLUSIONS: Drugs
      commonly used to treat PCOS appear to be associated with very low risk of severe
      adverse effects although data are extrapolated from other populations.

PMID- 24092832
TI  - Lifestyle modification programs in polycystic ovary syndrome: systematic review
      and meta-analysis.
AB  - CONTEXT: Polycystic ovary syndrome (PCOS) is a prevalent disorder that affects
      women of childbearing age and may be related to obesity and insulin resistance.
      OBJECTIVE: The purpose of this systematic review was to appraise the evidence of
      the impact of lifestyle modification (LSM) interventions on outcomes of women
      with PCOS. DATA SOURCES: Sources included Ovid Medline, OVID Embase, OVID
      Cochrane Library, Web of Science, Scopus, PsycINFO, and CINAHL (up to January
      2011). STUDY SELECTION: We included randomized controlled trials that enrolled
      woman of any age with PCOS who received LSM and compared them against women who
      received no intervention, minimal intervention, or metformin. DATA EXTRACTION:
      Two authors performed the data extraction independently. DATA SYNTHESIS: We
      included 9 trials enrolling 583 women with a high loss to follow-up rate, lack of
      blinding, and short follow-up. Compared with minimal intervention, LSM
      significantly reduced fasting blood glucose (weighted mean difference, -2.3
      mg/dL; 95% confidence interval, -4.5 to -0.1, I2 = 72%, P = .04) and fasting
      blood insulin (weighted mean difference, -2.1 MUU/mL, 95% confidence interval, 
      3.3 to -1.0, I2 = 0%, P < .001). Changes in body mass index were associated with
      changes in fasting blood glucose (P < .001). Metformin was not significantly
      better than LSM in improving blood glucose or insulin levels. We found no
      significant effect of LSM on pregnancy rate, and the effect on hirsutism was
      unclear. CONCLUSIONS: The available evidence suggests that LSM reduces fasting
      blood glucose and insulin levels in women with PCOS. Metformin has similar
      effects. Translation of these short-term effects to patient-important outcomes,
      beyond diabetes prevention, remains uncertain.

PMID- 24092833
TI  - A randomized trial of vitamin D3 supplementation in children: dose-response
      effects on vitamin D metabolites and calcium absorption.
AB  - CONTEXT: Changes in serum vitamin D metabolites and calcium absorption with
      varying doses of oral vitamin D3 in healthy children are unknown. OBJECTIVE: Our
      objective was to examine the dose-response effects of supplemental vitamin D3 on
      serum vitamin D metabolites and calcium absorption in children living at two U.S.
      latitudes. DESIGN: Black and white children (n = 323) participated in a multisite
      (U.S. latitudes 34 degrees  N and 40 degrees  N), triple-masked trial. Children
      were randomized to receive oral vitamin D3 (0, 400, 1000, 2000, and 4000 IU/d)
      and were sampled over 12 weeks in winter. Serum 25-hydroxyvitamin D (25(OH)D) and
      1,25-dihydroxyvitamin D (1,25(OH)2D) were measured using RIA and intact PTH
      (iPTH) by immunoradiometric assay. Fractional calcium absorption was determined
      from an oral stable isotope 44Ca (5 mg) in a 150-mg calcium meal. Nonlinear and
      linear regression models were fit for vitamin D metabolites, iPTH, and calcium
      absorption. RESULTS: The mean baseline 25(OH)D value for the entire sample was
      70.0 nmol/L. Increases in 25(OH)D depended on dose with 12-week changes ranging
      from -10 nmol/L for placebo to 76 nmol/L for 4000 IU. Larger 25(OH)D gains were
      observed for whites vs blacks at the highest dose (P < .01). Gains for 1,25(OH)2D
      were not significant (P = .07), and decreases in iPTH were not dose-dependent.
      There was no dose effect of vitamin D on fractional calcium absorption when
      adjusted for pill compliance, race, sex, or baseline 25(OH)D. CONCLUSION: Large
      increases in serum 25(OH)D with vitamin D3 supplementation did not increase
      calcium absorption in healthy children living at 2 different latitudes.
      Supplementation with 400 IU/d was sufficient to maintain wintertime 25(OH)D
      concentrations in healthy black, but not white, children.

PMID- 24092835
TI  - Maximum dose levels for the rodent comet assay to examine damage at the site of
      contact or to the gastrointestinal tract.
AB  - The comet assay can be applied to virtually any tissue and it has been noted that
      it can be particularly useful in evaluating directly acting genotoxins at their
      initial site of action. Consequently, it has become relatively common practice to
      use the stomach comet assay after oral administration to test chemicals that have
      given positive in vitro genotoxicity results in the absence of metabolic
      activation. However, to test nontoxic substances up to the limit doses of
      1000/2000mg/kg formulations approaching molar concentrations must be used
      resulting in the stomach mucosa being exposed to excessively high levels.
      Evidence is beginning to accumulate which shows positive results that do not
      indicate that potential carcinogenicity may be associated with such high levels
      of exposure. For pharmaceutical agents, toxicokinetic data are usually available
      to demonstrate systemic exposure after oral administration. In such cases, it is
      proposed that exposure of any tissue to levels of the drug substance greater than
      those that have given positive in vitro results in the absence of metabolic
      activation is sufficient. However, it is recognised that toxicokinetic data are
      not available for all chemicals and there are also agents designed not to leave
      the gastrointestinal tract (GIT). Where it is necessary to examine the GIT, the
      dose levels selected for examination should cover the likely or intended exposure
      levels, not necessarily to achieve the maximum tolerated or limit doses, even if
      the higher doses are required for genotoxicity endpoints in other tissues to be
      valid. There are usually two or three dose levels in in vivo genotoxicity
      studies, so when both systemically exposed tissues and the stomach are being
      examined, it would be possible to use one of the lower doses for the latter
      without increasing the numbers of animals required. It is important to consider
      the local concentrations achieved in the stomach or other parts of the GIT in
      order to avoid the comet assay generating artefactual positive results and it is
      hoped this will be addressed in the imminent Organisation for Economic Co
      operation and Development guideline. 

PMID- 24092834
TI  - The postprandial rise in plasma cortisol in men is mediated by macronutrient
      specific stimulation of adrenal and extra-adrenal cortisol production.
AB  - CONTEXT: Circadian variation is a fundamental characteristic of plasma
      glucocorticoids, with a postprandial rise in cortisol an important feature. The
      diurnal rhythm is presumed to reflect alterations in hypothalamic-pituitary
      adrenal axis activity; however, cortisol is produced not only by the adrenal
      glands but also by regeneration from cortisone by the enzyme 11beta
      hydroxysteroid dehydrogenase type 1, mainly in liver and adipose tissue.
      OBJECTIVE: We tested the contribution of peripheral cortisol regeneration to
      macronutrient-induced circadian variation of plasma cortisol in humans. DESIGN:
      This was a randomized, single-blinded, crossover study. SETTING: The study was
      conducted at a hospital research facility. PARTICIPANTS: Eight normal-weight
      healthy men participated in the study. INTERVENTIONS: Subjects were given
      isocaloric energy isodense flavor-matched liquid meals composed of carbohydrate,
      protein, fat, or low-calorie placebo during infusion of the stable isotope tracer
      9,11,12,12-[2H]4-cortisol. OUTCOME MEASURES AND RESULTS: Plasma cortisol
      increased similarly after all macronutrient meals (by ~90 nmol/L) compared with
      placebo. Carbohydrate stimulated adrenal secretion and extra-adrenal regeneration
      of cortisol to a similar degree. Protein and fat meals stimulated adrenal
      cortisol secretion to a greater degree than extra-adrenal cortisol regeneration.
      The increase in cortisol production by 11beta-hydroxysteroid dehydrogenase type 1
      was in proportion to the increase in insulin. The postprandial cortisol rise was
      not accounted for by decreased cortisol clearance. CONCLUSIONS: Food-induced
      circadian variation in plasma cortisol is mediated by adrenal secretion and extra
      adrenal regeneration of cortisol. Given that the latter has the more potent
      effect on tissue cortisol concentrations and that effects on adrenal and extra
      adrenal cortisol production are macronutrient specific, this novel mechanism may
      contribute to the physiological interplay between insulin and glucocorticoids and
      the contrasting effects of certain diets on postprandial metabolism.

PMID- 24092836
TI  - Evaluating the role of conserved amino acids in bacterial O
      oligosaccharyltransferases by in vivo, in vitro and limited proteolysis assays.
AB  - Bacterial O-Oligosaccharyltransferases (O-OTases) constitute a growing family of
      enzymes that catalyze the transfer of a glycan from a lipid carrier to protein
      acceptors. O-OTases are inner membrane proteins that display limited sequence
      similarity, except for the Wzy_C signature domain also present in a predicted
      periplasmic loop of the WaaL ligase, the enzyme responsible for transferring the
      O antigen to the lipid A core. The mechanism of O-OTase-dependent glycosylation
      is poorly understood. In this work, conserved amino acid residues in the O-OTases
      were replaced with alanine in PglL, the O-OTase of Neisseria meningitidis. The
      activity of wild-type PglL and its mutant derivatives were analyzed in vivo in
      engineered Escherichia coli cells, and in in vitro assays. We identified two
      additional sites of pilin glycosylated exclusively by PglL in E. coli. Both sites
      are modified with phosphoglycerol (PG) by different enzymes in Neisseria
      gonorrhoeae and Neisseria meningitidis. Limited proteolysis experiments revealed
      a conformational change that is triggered upon interaction of the C-terminal
      region of PglL with the lipid-linked oligosaccharide (LLO) substrate. These
      experiments showed that Q178 and Y405 are required for optimal function, whereas
      H349 is essential for activity and plays a critical role in the interaction with
      LLO. The equivalent His residue is also essential for WaaL activity, which
      suggests a common mechanism for both enzymes, and supports the hypothesis that O
      glycosylation and lipopolysaccharide (LPS) synthesis are evolutionarily related.
      These results contribute to the elucidation of the mechanism of O-OTases, which
      are promising targets for novel antibiotics and present an enormous potential for
      glycoengineering novel vaccines and therapeutics.

PMID- 24092837
TI  - N-/O-glycosylation analysis of human FVIIa produced in the milk of transgenic
      rabbits.
AB  - Human coagulation factor VIIa is a glycoprotein that promotes haemostasis through
      activation of the coagulation cascade extrinsic pathway. Most haemophilia A/B
      patients with inhibitors are treated by injection of plasma-derived or
      recombinant FVIIa. The use of recombinant products raises questions about the
      ability of the host cell to produce efficiently post-translationally modified
      proteins. Glycosylation is especially critical considering that it can modulate
      protein safety and efficacy. The present paper reports the N-/O-glycosylation
      pattern of a new recombinant human factor VIIa expressed in the mammary glands of
      transgenic rabbits. Glycosylation was investigated by chromatography and advanced
      mass spectrometry techniques for glycan identification and quantitation. Mass
      spectrometry (MS)/MS analyses were performed to confirm the glycan structures as
      well as the position and branching of specific monosaccharides or substituents.
      The two N-glycosylation sites were found to be fully occupied mostly by mono- and
      bi-sialylated biantennary complex-type structures, the major form being
      A(2)G(2)S(1). Some oligomannose/hybrid structures were retrieved in lower
      abundance, the major ones being GlcNAcalpha1,O-phosphorylated at the C6-position
      of a Man residue (Man-6-(GlcNAcalpha1,O-)phosphate motif) as commonly observed on
      lysosomal proteins. No immunogenic glycotopes such as Galili (Galalpha1,3Gal) and
      HD antigens (N-glycolylneuraminic acid (NeuGc)) were detected. Concerning O
      glycosylation, the product exhibited O-fucose and O-glucose-(xylose)(0, 1, 2)
      motifs as expected. The N-glycosylation consistency was also investigated by
      varying production parameters such as the period of lactation, the number of
      consecutive lactations and rabbit generations. Results show that the transgenesis
      technology is suitable for the long-term production of rhFVIIa with a
      reproducible glycosylation pattern.

PMID- 24092838
TI  - Loneliness, friendship, and well-being in adults with autism spectrum disorders.
AB  - This study examined the relations among loneliness, friendship, and emotional
      functioning in adults (N = 108) with autism spectrum disorders. Participants
      completed self-report measures of symptoms of autism spectrum disorders,
      loneliness, number and nature of friendships, depression, anxiety, life
      satisfaction, and self-esteem. The results indicated that loneliness was
      associated with increased depression and anxiety and decreased life satisfaction
      and self-esteem, even after controlling for symptoms of autism spectrum
      disorders. In addition, greater quantity and quality of friendships were
      associated with decreased loneliness among adults with autism spectrum disorders.
      Multivariate models indicated that friendship did not moderate the relationship
      between loneliness and well-being; however, number of friends provided unique
      independent effects in predicting self-esteem, depression, and anxiety above and
      beyond the effects of loneliness. This was the first study to examine the
      relations among these aspects of social and emotional functioning in adults with
      autism spectrum disorders, and the results indicate that this topic warrants
      further clinical and research attention. 

PMID- 24092839
TI  - Using Tic-Tac software to reduce anxiety-related behaviour in adults with autism
      and learning difficulties during waiting periods: a pilot study.
AB  - Deficits in the perception of time and processing of changes across time are
      commonly observed in individuals with autism. This pilot study evaluated the
      efficacy of the use of the software tool Tic-Tac, designed to make time visual,
      in three adults with autism and learning difficulties. This research focused on
      applying the tool in waiting situations where the participants exhibited anxiety
      related behaviour. The intervention followed a baseline and intervention (AB)
      design, and a partial interval recording procedure was used to code the presence
      of stereotypes, nervous utterances, wandering or other examples of nervousness
      during the selected waiting situations. The results showed that the use of Tic
      Tac resulted in lower levels of anxiety-related behaviour in all three
      participants, compared to the baseline, suggesting that this software may be an
      effective technology for helping people with autism with organisation and
      predictability during waiting periods. The results are discussed in terms of
      limitations and implications for further study. 

PMID- 24092840
TI  - Family-focused autism spectrum disorder research: a review of the utility of
      family systems approaches.
AB  - A family member with an autism spectrum disorder presents pervasive and
      bidirectional influences on the entire family system, suggesting a need for
      family-focused autism spectrum disorder research. While there has been increasing
      interest in this research area, family-focused autism spectrum disorder research
      can still be considered relatively recent, and there are limitations to the
      existing literature. The purpose of this article is to provide theoretical and
      methodological directions for future family-focused autism spectrum disorder
      research. In particular, this article proposes Family Systems approaches as a
      common theoretical framework for future family-focused autism spectrum disorder
      research by considering theoretical concepts such as Boundaries, Ambiguous Loss,
      Resilience and Traumatic Growth. We discuss reasons why these concepts are
      important to researching families living with autism spectrum disorder and
      provide recommendations for future research. The potential for research grounded
      in Family Systems approaches to influence clinical support services is also
      discussed. 

PMID- 24092841
TI  - Maladaptive cognitive appraisals in children with high-functioning autism:
      associations with fear, anxiety and theory of mind.
AB  - Despite the well-documented success of cognitive restructuring techniques in the
      treatment of anxiety disorders, there is still little clarity on which cognitions
      underpin fear and anxiety in children with high-functioning autism spectrum
      disorder. This study examined whether certain cognitive appraisals, known to be
      associated with fear and anxiety in typically developing groups, may help explain
      these emotions in children with high-functioning autism spectrum disorder. It
      also investigated relations between these cognitive appraisals and theory of
      mind. Appraisals, fear and anxiety were assessed using a vignette approach in 22
      children with high-functioning autism spectrum disorders and 22 typically
      developing children. The two groups differed significantly on all four appraisal
      types. Anxiety was negatively correlated with future expectancy and positively
      with problem-focused coping potential in the high-functioning autism spectrum
      disorder group but was not correlated with appraisals in the typically developing
      group. The two appraisals associated with fear were emotion-focused coping
      potential (in the high-functioning autism spectrum disorder group only) and self
      accountability (in the typically developing group only). Linear regression
      analysis found that appraisals of emotion-focused coping potential, problem
      focused coping potential and future expectancy were significant predictors of
      theory-of-mind ability in the high-functioning autism spectrum disorders group.
      These findings indicate that specific, problematic patterns of appraisal may
      characterise children with high-functioning autism spectrum disorders. 

PMID- 24092842
TI  - Verbal fluency in children with autism spectrum disorders: clustering and
      switching strategies.
AB  - This study highlights differences in cognitive strategies in children and
      adolescents with and without autism spectrum disorders (n = 52) on a verbal
      fluency task (naming as many words as possible (e.g. animals) within 60 s). The
      ability to form clusters of words (e.g. farm animals like "cow-horse-goat") or to
      switch between unrelated words (e.g. "snake" and "cat") was analyzed using a
      coding method that more stringently differentiates between these strategies.
      Results indicated that children and adolescents with autism spectrum disorders
      switched less frequently, but produced slightly larger clusters than the
      comparison group, resulting in equal numbers of total words produced. The
      currently used measures of cognitive flexibility suggest atypical, but possibly
      equally efficient, fluency styles used by individuals with autism spectrum
      disorders. 

PMID- 24092843
TI  - Innovative technology-based interventions for autism spectrum disorders: a meta
      analysis.
AB  - This article reports the results of a meta-analysis of technology-based
      intervention studies for children with autism spectrum disorders. We conducted a
      systematic review of research that used a pre-post design to assess innovative
      technology interventions, including computer programs, virtual reality, and
      robotics. The selected studies provided interventions via a desktop computer,
      interactive DVD, shared active surface, and virtual reality. None employed
      robotics. The results provide evidence for the overall effectiveness of
      technology-based training. The overall mean effect size for posttests of
      controlled studies of children with autism spectrum disorders who received
      technology-based interventions was significantly different from zero and
      approached the medium magnitude, d = 0.47 (confidence interval: 0.08-0.86). The
      influence of age and IQ was not significant. Differences in training procedures
      are discussed in the light of the negative correlation that was found between the
      intervention durations and the studies' effect sizes. The results of this meta
      analysis provide support for the continuing development, evaluation, and clinical
      usage of technology-based intervention for individuals with autism spectrum
      disorders. 

PMID- 24092844
TI  - Distribution of pneumococcal serotypes in adult pneumococcal pneumonia cases:
      filling the evidence gap to inform vaccination policies.

PMID- 24092845
TI  - Distribution of 13-valent pneumococcal conjugate vaccine Streptococcus pneumoniae
      serotypes in US adults aged >=50 years with community-acquired pneumonia.
AB  - BACKGROUND: Streptococcus pneumoniae causes a substantial proportion of community
      acquired pneumonia (CAP) and healthcare-associated pneumonia (HCAP) in the United
      States. Limited data are available regarding the pneumococcal serotypes causing
      CAP and HCAP. METHODS: Adults aged >= 50 years presenting to participating US
      hospitals with radiographically confirmed pneumonia between February 2010 and
      September 2011 were screened for inclusion. S. pneumoniae was identified using
      microbiological cultures, BinaxNOW(r) S. pneumoniae assay, or urine antigen
      detection (UAD) assay capable of detecting 13-valent pneumococcal conjugate
      vaccine (PCV13)-associated serotypes. RESULTS: Among 710 subjects enrolled, the
      median age was 65.4 years; 54.2% of subjects were male, 22.4% of radiographically
      confirmed pneumonia cases were considered HCAP, and 96.6% of subjects were
      hospitalized. S. pneumoniae was detected in 98 subjects (13.8%) by any test, and
      PCV13-associated serotype(s) were identified by UAD in 78 (11.0%). Serotype 19A
      was most prevalent, followed by 7F/A, 3, and 5. Serotypes associated with 7
      valent pneumococcal conjugate vaccine (PCV7) accounted for 25% of UAD-positive
      isolates. CONCLUSIONS: Pneumococcal serotypes causing noninvasive pneumonia in
      adults may differ significantly from those causing invasive disease, with PCV7
      associated serotypes overrepresented. Serotype 5, rarely seen in contemporary
      surveillance of invasive disease in the United States, substantially contributed
      to the observed cases of S. pneumoniae-positive CAP or HCAP.

PMID- 24092846
TI  - Effects of weight loss on renal function in obese CKD patients: a systematic
      review.
AB  - Obesity is an independent risk factor for the development and progression of
      chronic kidney disease (CKD). We conducted a systematic review to assess the
      benefits of intentional weight loss in obese subjects with altered glomerular
      filtration rate (GFR), proteinuria or albuminuria. MEDLINE, EMBASE and CENTRAL
      databases were searched for articles reporting longitudinal data on the effect of
      weight loss on renal parameters in obese patients with altered kidney function.
      Thirty-one (2013 subjects) were included. In the 13 studies where weight loss was
      achieved by bariatric surgery, body mass index (BMI) significantly decreased in
      all studies; GFR decreased in six studies on hyperfiltration patients and
      increased in one study on patients with CKD Stage 3-4. Albuminuria decreased in
      six studies and proteinuria decreased in five studies. In six studies, weight
      loss was achieved by antiobesity agents: BMI decreased in all studies; GFR
      decreased in four studies and albuminuria in three. Eleven studies analysed the
      effects of diet, alone or in combination with lifestyle modifications. A
      significant decrease in BMI was reported in all studies; GFR increased in two
      studies, remained stable in four studies and decreased in two studies on
      hyperfiltration patients. Albuminuria decreased in six studies and remained
      stable in one study. Proteinuria decreased in five studies. In obese patients
      with altered renal function, weight loss, particularly if achieved by surgical
      interventions, improves proteinuria, albuminuria and normalizes GFR. Larger, long
      term studies are needed to analyse the durability of this improvement and the
      effects on renal outcomes, such as CKD progression and the development of ESKD. 

PMID- 24092847
TI  - The impact of dietary magnesium restriction on magnesiotropic and calciotropic
      genes.
AB  - BACKGROUND: Magnesium (Mg(2+)) is an essential electrolyte with important
      physiological functions. Consequently, hypomagnesaemia, an electrolyte disorder
      frequently diagnosed in critically ill patients, can have life-threatening
      consequences. The kidney plays a central role in the regulation of the Mg(2+)
      balance. The present study investigated the molecular consequences of dietary
      Mg(2+) restriction on renal Mg(2+) transporters. METHODS: Two groups of 10 mice
      were fed a Mg(2+)-deficient diet or a Mg(2+)-enriched diet for 2 weeks. Serum and
      urine electrolyte concentrations were assayed. Next, renal mRNA expression levels
      of Mg(2+)-related genes were measured to determine their sensitivity to the
      dietary Mg(2+) content. Subsequently, parvalbumin (PV) and the thiazide-sensitive
      Na(+)-Cl(-) cotransporter (NCC), both co-expressed in the distal convoluted
      tubule (DCT) with TRPM6, were further analysed at the protein level using
      immunoblotting and immunohistochemistry. RESULTS: Serum and urine electrolyte
      measurements revealed that dietary Mg(2+) restriction resulted in significant
      reduction of serum Mg(2+) and Ca(2+) levels, and that the urinary excretion of
      these ions was also markedly reduced, while phosphate (Pi) excretion was
      significantly increased. In addition, the serum FGF23 level was markedly
      increased, whereas Pi was not significantly changed in the Mg(2+)-restricted
      mouse group. The renal abundance of hepatocyte nuclear factor 1 homeobox B
      (HNF1B) and the epithelial Mg(2+) channel TRPM6 were increased in response to
      dietary Mg(2+) restriction, whereas other magnesiotropic transporters were not
      affected. PV abundance was upregulated, while NCC was significantly
      downregulated. Furthermore, the expression levels of the epithelial Ca(2+)
      channel TRPV5 and calbindin-D28K were markedly reduced in the low Mg(2+) group.
      CONCLUSIONS: Our data indicate an essential adaptive role for DCT during
      hypomagnesaemia since TRPM6, HNF1B, PV and NCC expression levels were adjusted.
      Moreover, hypomagnesaemia resulted in severe changes in Ca(2+) and Pi
      reabsorption and expression levels of calciotropic proteins.

PMID- 24092848
TI  - The prevalence of chronic kidney disease and its relation to socioeconomic
      conditions in an elderly Polish population: results from the national population
      based study PolSenior.
AB  - BACKGROUND: Rapidly progressing ageing of worldwide populations is likely to
      increase the occurrence of chronic kidney disease (CKD) in the next decades.
      However, until now little is known about the prevalence of CKD in the Polish
      elderly population. The aim of this study was to assess the prevalence of CKD and
      its relation to socioeconomic conditions in the Polish elderly population.
      METHODS: A glomerular filtration rate estimated (eGFR) according to the CKD-EPI
      formula and urine albumin/creatinine ratio were determined in 3797 out of 4979
      randomly selected elderly subjects from the national survey study PolSenior.
      Additionally, some socioeconomic factors related to the prevalence of CKD were
      also analysed. RESULTS: The prevalence of CKD in the Polish elderly population
      was 29.4%. Only 3.2% of elderly subjects with CKD were aware of the disease. CKD
      was more frequent among urban dwellers, non-smokers, alcohol abstinents and those
      with low physical activity. Decreased eGFR was more frequent among less educated
      women, better educated men, blue collar female workers and white collar male
      workers. Increased albuminuria was associated with low physical activity.
      CONCLUSIONS: (i) CKD affects almost one-third of the elderly Polish population.
      (ii) In Poland elderly subjects with CKD are usually unaware of their kidney
      disease. (iii) In Polish elderly population, CKD is more frequently present among
      urban residents, non-smokers, abstainers and less physically active people. (iv)
      Only in women is higher educational status related to the lower risk of CKD.

PMID- 24092849
TI  - Echocardiographical determinants of an abnormal spatial QRS-T angle in chronic
      dialysis patients.
AB  - BACKGROUND: The spatial QRS-T angle describes the relation between ventricular
      depolarization and repolarization. Having a wide (abnormal) angle is considered
      an important predictor of arrhythmic events. Given the high incidence of sudden
      cardiac death in dialysis patients, this parameter is of particular interest in
      this patient group. The objective of this study was to assess the association of
      (modifiable) echocardiographic parameters and an abnormal spatial QRS-T angle in
      dialysis patients. METHODS: A total of 94 consecutive dialysis patients were
      included. In all patients a 12-lead electrocardiogram (ECG), a two-dimensional
      echocardiogram and routine blood samples were obtained. The spatial QRS-T angle
      was then calculated from the 12-lead ECG. An abnormal spatial QRS-T angle was
      defined as >=130 degrees  in males and >=116 degrees  in females. RESULTS: An
      abnormal spatial QRS-T angle was present in 27 (29%) patients. Patients with an
      abnormal spatial angle had a lower left ventricular ejection fraction (LVEF) of
      47 +/- 7 versus 55 +/- 6% (P < 0.001) and had a higher left ventricular (LV)
      dyssynchrony, with a septal to lateral (S-L) delay of peak systolic velocity of
      70 inter quartile range (iIQR) (40, 100) ms versus 30 IQR (10, 70) ms (P =
      0.001), respectively. Multivariate logistic regression analysis controlling for
      possible confounders demonstrated that LVEF [odds ratio (OR) 0.82; 95% confidence
      interval (CI) 0.72-0.93, P = 0.001] and LV dyssynchrony (OR 1.19 per 10 ms; 95%
      CI 1.03-1.38, P = 0.02) were independent determinants of an abnormal spatial QRS
      T angle in this patient group. CONCLUSIONS: LVEF and dyssynchrony are
      echocardiographic determinants of an abnormal spatial QRS-T angle in dialysis
      patients and might therefore represent a potential target for the prevention of
      sudden cardiac death in these patients.

PMID- 24092851
TI  - Clinical utility of viral load in management of cytomegalovirus infection after
      solid organ transplantation.
AB  - The negative impact of cytomegalovirus (CMV) infection on transplant outcomes
      warrants efforts toward improving its prevention, diagnosis, and treatment.
      During the last 2 decades, significant breakthroughs in diagnostic virology have
      facilitated remarkable improvements in CMV disease management. During this
      period, CMV nucleic acid amplification testing (NAT) evolved to become one of the
      most commonly performed tests in clinical virology laboratories. NAT provides a
      means for rapid and sensitive diagnosis of CMV infection in transplant
      recipients. Viral quantification also introduced several principles of CMV
      disease management. Specifically, viral load has been utilized (i) for
      prognostication of CMV disease, (ii) to guide preemptive therapy, (iii) to assess
      the efficacy of antiviral treatment, (iv) to guide the duration of treatment, and
      (v) to indicate the risk of clinical relapse or antiviral drug resistance.
      However, there remain important limitations that require further optimization,
      including the interassay variability in viral load reporting, which has limited
      the generation of standardized viral load thresholds for various clinical
      indications. The recent introduction of an international reference standard
      should advance the major goal of uniform viral load reporting and interpretation.
      However, it has also become apparent that other aspects of NAT should be
      standardized, including sample selection, nucleic acid extraction, amplification,
      detection, and calibration, among others. This review article synthesizes the
      vast amount of information on CMV NAT and provides a timely review of the
      clinical utility of viral load testing in the management of CMV in solid organ
      transplant recipients. Current limitations are highlighted, and avenues for
      further research are suggested to optimize the clinical application of NAT in the
      management of CMV after transplantation.

PMID- 24092852
TI  - Pathogenesis and current approaches to control of varicella-zoster virus
      infections.
AB  - Varicella-zoster virus (VZV) was once thought to be a fairly innocuous pathogen.
      That view is no longer tenable. The morbidity and mortality due to the primary
      and secondary diseases that VZV causes, varicella and herpes zoster (HZ), are
      significant. Fortunately, modern advances, including an available vaccine to
      prevent varicella, a therapeutic vaccine to diminish the incidence and ameliorate
      sequelae of HZ, effective antiviral drugs, a better understanding of VZV
      pathogenesis, and advances in diagnostic virology have made it possible to
      control VZV in the United States. Occult forms of VZV-induced disease have been
      recognized, including zoster sine herpete and enteric zoster, which have expanded
      the field. Future progress should include development of more effective vaccines
      to prevent HZ and a more complete understanding of the consequences of VZV
      latency in the enteric nervous system.

PMID- 24092853
TI  - Trends in human fecal carriage of extended-spectrum beta-lactamases in the
      community: toward the globalization of CTX-M.
AB  - In the last 10 years, extended-spectrum beta-lactamase-producing enterobacteria
      (ESBL-E) have become one of the main challenges for antibiotic treatment of
      enterobacterial infections, largely because of the current CTX-M enzyme pandemic.
      However, most studies have focused on hospitalized patients, though today it
      appears that the community is strongly affected as well. We therefore decided to
      devote our investigation to trends in ESBL-E fecal carriage rates and
      comprehensively reviewed data from studies conducted on healthy populations in
      various parts of the world. We show that (i) community ESBL-E fecal carriage,
      which was unknown before the turn of the millennium, has since increased
      significantly everywhere, with developing countries being the most affected; (ii)
      intercontinental travel may have emphasized and globalized the issue; and (iii)
      CTX-M enzymes, especially CTX-M-15, are the dominant type of ESBL. Altogether,
      these results suggest that CTX-M carriage is evolving toward a global pandemic
      but is still insufficiently described. Only a better knowledge of its dynamics
      and biology will lead to further development of appropriate control measures.

PMID- 24092850
TI  - Update on tick-borne rickettsioses around the world: a geographic approach.
AB  - Tick-borne rickettsioses are caused by obligate intracellular bacteria belonging
      to the spotted fever group of the genus Rickettsia. These zoonoses are among the
      oldest known vector-borne diseases. However, in the past 25 years, the scope and
      importance of the recognized tick-associated rickettsial pathogens have increased
      dramatically, making this complex of diseases an ideal paradigm for the
      understanding of emerging and reemerging infections. Several species of tick
      borne rickettsiae that were considered nonpathogenic for decades are now
      associated with human infections, and novel Rickettsia species of undetermined
      pathogenicity continue to be detected in or isolated from ticks around the world.
      This remarkable expansion of information has been driven largely by the use of
      molecular techniques that have facilitated the identification of novel and
      previously recognized rickettsiae in ticks. New approaches, such as swabbing of
      eschars to obtain material to be tested by PCR, have emerged in recent years and
      have played a role in describing emerging tick-borne rickettsioses. Here, we
      present the current knowledge on tick-borne rickettsiae and rickettsioses using a
      geographic approach toward the epidemiology of these diseases.

PMID- 24092854
TI  - A current perspective on daptomycin for the clinical microbiologist.
AB  - Daptomycin is a lipopeptide antimicrobial with in vitro bactericidal activity
      against Gram-positive bacteria that was first approved for clinical use in 2004
      in the United States. Since this time, significant data have emerged regarding
      the use of daptomycin for the treatment of serious infections, such as bacteremia
      and endocarditis, caused by Gram-positive pathogens. However, there are also
      increasing reports of daptomycin nonsusceptibility, in Staphylococcus aureus and,
      in particular, Enterococcus faecium and Enterococcus faecalis. Such
      nonsusceptibility is largely in the context of prolonged treatment courses and
      infections with high bacterial burdens, but it may occur in the absence of prior
      daptomycin exposure. Nonsusceptibility in both S. aureus and Enterococcus is
      mediated by adaptations to cell wall homeostasis and membrane phospholipid
      metabolism. This review summarizes the data on daptomycin, including daptomycin's
      unique mode of action and spectrum of activity and mechanisms for
      nonsusceptibility in key pathogens, including S. aureus, E. faecium, and E.
      faecalis. The challenges faced by the clinical laboratory in obtaining accurate
      susceptibility results and reporting daptomycin MICs are also discussed.

PMID- 24092855
TI  - Salivary biomarkers: toward future clinical and diagnostic utilities.
AB  - The pursuit of timely, cost-effective, accurate, and noninvasive diagnostic
      methodologies is an endeavor of urgency among clinicians and scientists alike.
      Detecting pathologies at their earliest stages can significantly affect patient
      discomfort, prognosis, therapeutic intervention, survival rates, and recurrence.
      Diagnosis and monitoring often require painful invasive procedures such as
      biopsies and repeated blood draws, adding undue stress to an already unpleasant
      experience. The discovery of saliva-based microbial, immunologic, and molecular
      biomarkers offers unique opportunities to bypass these measures by utilizing oral
      fluids to evaluate the condition of both healthy and diseased individuals. Here
      we discuss saliva and its significance as a source of indicators for local,
      systemic, and infectious disorders. We highlight contemporary innovations and
      explore recent discoveries that deem saliva a mediator of the body's
      physiological condition. Additionally, we examine the current state of salivary
      diagnostics and its associated technologies, future aspirations, and potential as
      the preferred route of disease detection, monitoring, and prognosis.

PMID- 24092856
TI  - Investigational antimicrobial agents of 2013.
AB  - New antimicrobial agents are always needed to counteract the resistant pathogens
      that continue to be selected by current therapeutic regimens. This review
      provides a survey of known antimicrobial agents that were currently in clinical
      development in the fall of 2012 and spring of 2013. Data were collected from
      published literature primarily from 2010 to 2012, meeting abstracts (2011 to
      2012), government websites, and company websites when appropriate. Compared to
      what was reported in previous surveys, a surprising number of new agents are
      currently in company pipelines, particularly in phase 3 clinical development.
      Familiar antibacterial classes of the quinolones, tetracyclines, oxazolidinones,
      glycopeptides, and cephalosporins are represented by entities with enhanced
      antimicrobial or pharmacological properties. More importantly, compounds of novel
      chemical structures targeting bacterial pathways not previously exploited are
      under development. Some of the most promising compounds include novel beta
      lactamase inhibitor combinations that target many multidrug-resistant Gram
      negative bacteria, a critical medical need. Although new antimicrobial agents
      will continue to be needed to address increasing antibiotic resistance, there are
      novel agents in development to tackle at least some of the more worrisome
      pathogens in the current nosocomial setting.

PMID- 24092860
TI  - Overexpressed let-7a inhibits glioma cell malignancy by directly targeting K-ras,
      independently of PTEN.
AB  - BACKGROUND: Altered expression of micro(mi)RNAs has been shown to be associated
      with tumorigenesis and tumor progression. The expression of phosphatase and
      tensin homolog (PTEN) plays an important role in glioma and is regarded as a
      prognostic marker of glioma patients. The goal of this study was to investigate
      the function of lethal (let)-7a miRNA in glioma cell lines with different PTEN
      phenotypes. METHODS: One hundred ninety-eight glioma tissues were used to profile
      miRNA expression. RESULTS: Let-7a was shown to have lower expression in high
      grade glioma than in low-grade glioma. Low expression of let-7a was correlated
      with poor prognosis of primary glioblastoma patients. We demonstrated that K-ras
      was a functional target for let-7a to induce cell cycle arrest, apoptosis, and
      inhibition of cell migration and invasion in vitro. Our further results showed no
      difference in malignancy inhibition induced by let-7a in 4 glioma cells,
      including U87 (PTEN null), U251 (PTEN mutant), LN229 (PTEN wild type), and LN229
      (PTEN small interfering RNA). The phosphatidylinositol-3 kinase/Akt and mitogen
      activated protein kinase/extracellular signal-regulated kinase pathways were
      inhibited by let-7a, and the inhibition effects had no difference in 4 glioma
      cells. We demonstrated that let-7a could induce suppression of glioma in vivo by
      generating a glioma xenograft model. CONCLUSION: Our results indicated that let
      7a suppresses its target transcript K-ras and inhibits glioma malignancy
      independent of PTEN expression.

PMID- 24092861
TI  - Barrett's oesophagus: epidemiology, cancer risk and implications for management.
AB  - Although endoscopic surveillance of patients with Barrett's oesophagus has been
      widely implemented, its effectiveness is debateable. The recently reported low
      annual oesophageal adenocarcinoma risk in population studies, the failure to
      identify most Barrett's patients at risk of disease progression, the poor
      adherence to surveillance and biopsy protocols, and the significant risk of
      misclassification of dysplasia all tend to undermine the effectiveness of current
      management, in particular, endoscopic surveillance programmes, to prevent or
      improve the outcomes of patients with oesophageal adenocarcinoma. The ongoing
      increase in incidence of Barrett's oesophagus and consequent growth of the
      surveillance population, together with the associated discomfort and costs of
      endoscopic surveillance, demand improved techniques for accurately determining
      individual risk of oesophageal adenocarcinoma. More accurate techniques are
      needed to run efficient surveillance programmes in the coming decades. In this
      review, we will discuss the current knowledge on the epidemiology of Barrett's
      oesophagus, and the challenging epidemiological dilemmas that need to be
      addressed when assessing the current screening and surveillance strategies. 

PMID- 24092859
TI  - Quinacrine synergistically enhances the antivascular and antitumor efficacy of
      cediranib in intracranial mouse glioma.
AB  - BACKGROUND: Despite malignant glioma vascularity, anti-angiogenic therapy is
      largely ineffective. We hypothesize that efficacy of the antiangiogenic agent
      cediranib is synergistically enhanced in intracranial glioma via combination with
      the late-stage autophagy inhibitor quinacrine. METHODS: Relative cerebral blood
      flow and volume (rCBF, rCBV), vascular permeability (K(trans)), and tumor volume
      were assessed in intracranial 4C8 mouse glioma using a dual-bolus perfusion MRI
      approach. Tumor necrosis and tumor mean vessel density (MVD) were assessed
      immunohistologically. Autophagic vacuole accumulation and apoptosis were assessed
      via Western blot in 4C8 glioma in vitro. RESULTS: Cediranib or quinacrine
      treatment alone did not alter tumor growth. Survival was only marginally improved
      by cediranib and unchanged by quinacrine. In contrast, combined
      cediranib/quinacrine reduced tumor growth by >2-fold (P < .05) and increased
      median survival by >2-fold, compared with untreated controls (P < .05). Cediranib
      or quinacrine treatment alone did not significantly alter mean tumor rCBF or
      K(trans) compared with untreated controls, while combined cediranib/quinacrine
      substantially reduced both (P < .05), indicating potent tumor devascularization.
      MVD and necrosis were unchanged by cediranib or quinacrine treatment. In
      contrast, MVD was reduced by nearly 2-fold (P < .01), and necrosis increased by 3
      fold (P < .05, one-tailed), in cediranib + quinacrine treated vs untreated
      groups. Autophagic vacuole accumulation was induced by cediranib and quinacrine
      in vitro. Combined cediranib/quinacrine treatment under hypoxic conditions
      induced further accumulation and apoptosis. CONCLUSION: Combined
      cediranib/quinacrine treatment synergistically increased antivascular/antitumor
      efficacy in intracranial 4C8 mouse glioma, suggesting a promising and facile
      treatment strategy for malignant glioma. Modulations in the autophagic pathway
      may play a role in the increased efficacy.

PMID- 24092862
TI  - p21 promotes sustained liver regeneration and hepatocarcinogenesis in chronic
      cholestatic liver injury.
AB  - BACKGROUND AND AIMS: The cyclin-dependent kinase inhibitor p21 has been
      implicated as a tumour suppressor. Moreover, recent genetic studies suggest that
      p21 might be a potential therapeutic target to improve regeneration in chronic
      diseases. The aim of this study was to delineate the role of p21 in chronic liver
      injury and to specify its role in hepatocarcinogenesis in a mouse model of
      chronic cholestatic liver injury. METHODS: The degree of liver injury,
      regeneration and tumour formation was assessed in Mdr2(-/-) mice and compared
      with Mdr2/ p21(-/-) mice. Moreover, the role of p21 was evaluated in hepatoma
      cells in vitro and in human hepatocellular carcinoma (HCC). RESULTS: Mdr2(-/-)
      mice developed HCCs as a consequence of chronic inflammatory liver injury. In
      contrast, tumour development was profoundly delayed in Mdr2/ p21(-/-) mice.
      Delayed tumour development was accompanied by markedly impaired liver
      regeneration in Mdr2/ p21(-/-) mice. Moreover, the regenerative capacity of the
      Mdr2/ p21(-/-) livers in response to partial hepatectomy declined with age in
      these mice. Hepatocyte transplantation experiments revealed that impaired liver
      regeneration was due to intrinsic factors within the cells and changes in the
      Mdr2/ p21(-/-) microenvironment. In human HCCs, a subset of tumours expressed
      p21, which was associated with a significant shorter patient survival.
      CONCLUSIONS: We provide experimental evidence that p21 is required for sustained
      liver regeneration and tumour development in chronic liver injury indicating that
      p21 needs to be tightly regulated in order to balance liver regeneration and
      cancer risk. Moreover, we identify p21 as a negative prognostic marker in human
      HCC.

PMID- 24092864
TI  - Curcumin against hepatitis C virus infection: spicing up antiviral therapies with
      'nutraceuticals'?

PMID- 24092863
TI  - Genetic and microbial factors modulating the ubiquitin proteasome system in
      inflammatory bowel disease.
AB  - OBJECTIVE: Altered microbiota composition, changes in immune responses and
      impaired intestinal barrier functions are observed in IBD. Most of these features
      are controlled by proteases and their inhibitors to maintain gut homeostasis.
      Unrestrained or excessive proteolysis can lead to pathological gastrointestinal
      conditions. The aim was to validate the identified protease IBD candidates from a
      previously performed systematic review through a genetic association study and
      functional follow-up. DESIGN: We performed a genetic association study in a large
      multicentre cohort of patients with Crohn's disease (CD) and UC from five
      European IBD referral centres in a total of 2320 CD patients, 2112 UC patients
      and 1796 healthy controls. Subsequently, we did an extensive functional
      assessment of the candidate genes to explore their causality in IBD pathogenesis.
      RESULTS: Ten single nucleotide polymorphisms (SNPs) in four genes were
      significantly associated with CD: CYLD, USP40, APEH and USP3. CYLD was the most
      significant gene with the intronically located rs12324931 the strongest
      associated SNP (p(FDR)=1.74e-17, OR=2.24 (1.83 to 2.74)). Five SNPs in four genes
      were significantly associated with UC: USP40, APEH, DAG1 and USP3. CYLD, as well
      as some of the other associated genes, is part of the ubiquitin proteasome system
      (UPS). We therefore determined if the IBD-associated adherent-invasive
      Escherichia coli (AIEC) can modulate the UPS functioning. Infection of intestinal
      epithelial cells with the AIEC LF82 reference strain modulated the UPS turnover
      by reducing poly-ubiquitin conjugate accumulation, increasing 26S proteasome
      activities and decreasing protein levels of the NF-kappaB regulator CYLD. This
      resulted in IkappaB-alpha degradation and NF-kappaB activation. This activity was
      very important for the pathogenicity of AIEC since decreased CYLD resulted in
      increased ability of AIEC LF82 to replicate intracellularly. CONCLUSIONS: Our
      results reveal the UPS, and CYLD specifically, as an important contributor to IBD
      pathogenesis, which is favoured by both genetic and microbial factors.

PMID- 24092865
TI  - Deep venous structures distortion in spontaneous intracranial hypotension as an
      explanation for altered level of consciousness.
AB  - Spontaneous intracranial hypotension (SIH) is a syndrome of low pressure headache
      associated with low CSF pressure. The condition is generally considered benign
      but extreme cases of SIH can lead to changes in the level of consciousness. We
      describe a case in which alteration in the level of consciousness was prolonged
      and severe, and could not be explained solely by the presence of subdural
      collections. MRI of the brain showed evidence of impaired venous flow secondary
      to brain sagging causing distortion of deep venous structures. 

PMID- 24092866
TI  - The effect of positioning on preterm infants' sleep-wake states and stress
      behaviours during exposure to environmental stressors.
AB  - Previous studies separately examined the effects of positioning or environmental
      stressors on preterm infants' sleep and stress. Since positioning and
      environmental stressors occur simultaneously during infant hospitalization
      exploring these variables in the same study may offer new insights. A quasi
      experimental study by one-group interrupted time-series design. In the current
      study, a total of 22 preterm infants were enrolled. Each infant was moved to
      either the supine or prone position for an hour at a time. Infants were
      videotaped and the sleep-wake states, stress behaviours and environmental
      conditions (light, noise and stimulation/handling) were recorded during the
      observation period. A total of 80 observations from 22 infants were accrued. In
      the supine position, preterm infants demonstrated more frequent waking states
      after adjusting for various environmental stressors (p < .01). These infants
      demonstrated more frequent stress behaviours in the supine position after
      adjusting for various environmental stressors (p < .01). These results suggest
      that the prone position is a more favourable position for facilitating sleep and
      reducing stress for preterm infants exposed to varying environmental stressors.
      Preterm infants present different stress behaviours in response to varying types
      of environmental stimuli.

PMID- 24092867
TI  - Unintentional injuries in child care centers in the United States: a systematic
      review.
AB  - The study systematically reviewed all types of unintentional injury and injury
      prevention research studies occurring within child care centers in the United
      States. A total of 2 reviewers searched 11 electronic databases to identify 53
      articles meeting inclusion criteria. No studies used trauma registries or
      randomized control trials. Data were not pooled for further analysis because
      studies lacked standardized definitions for injury, rates, severity, exposure,
      and demographics. The following child care center injury rates were reported:
      (0.25-5.31 injuries per 100,000 child-hours); (11.3-18 injuries per 100 children
      per year); (6-49 injuries per 1000 child-years); (2.5-8.29 injuries per child
      year); (2.6-3.3 injuries per child); (3.3-6.3 injuries per 100 observations);
      (635-835 medically attended injuries per year per 100,000 children and 271-364
      child care center playground injuries per year per 100,000 children); and (3.8
      injuries per child per 2000 exposure hours). Child care center injury rates were
      comparable to injury rates published for schools, playground, and summer camp.
      Most injuries were minor, while most severe injuries (fractures and concussions)
      were falls from playground structures. Future studies need to use standardized
      injury definitions and injury severity scales, focus efforts on preventing severe
      playground injuries in child care centers, and report child care parameters for
      inclusion in national injury databases. 

PMID- 24092868
TI  - Drowning risk perceptions among rural guardians of Thailand: A community-based
      household survey.
AB  - Drowning is one of the most common causes of death among young children in
      Thailand. Children in primary school in rural settings have a high rate of fatal
      drowning. Guardians' perceptions are important since children are normally in
      their care. This study aims to describe drowning risk perceptions of guardians
      and to identify barriers to developing a child's swimming skills. A cross
      sectional household survey was conducted among guardians of children who attended
      12 schools serving 48 villages in a rural community. The results revealed that
      less than one-fifth (18%) of children in the household could swim. Guardians
      reported that children should learn to swim at the age of seven years. About one
      quarter (23%) of guardians did not perceive drowning as the leading cause of
      death among children. More than a quarter (25.4%) perceived that their child was
      not at the risk of drowning. No statistical differences were reported on drowning
      perception among guardians with different swimming skills as well as child's
      swimming skill. Significantly more parents of children who could not swim
      perceived lack of swimming instructors, clean water and school swimming lessons
      as barriers to a child's acquisition of swimming skill. The results highlight the
      need to consider improving the infrastructure in rural areas to facilitate
      swimming skills for school children to reduce drowning risk. 

PMID- 24092869
TI  - Two methods of cord care in high-risk newborns: their effects on hydration,
      temperature, pH, and floras of the cord area.
AB  - This randomized clinical study explored the effects of two cord care methods on
      hydration, temperature, pH, and floras at the cord area in high-risk newborns.
      One group used the water method; and the other group used the alcohol method.
      Seventy-two newborns, including premature newborns, in the neonatal intensive
      care unit (NICU) of a university-affiliated hospital in South Korea were enrolled
      from August 2011 to May 2012. Hydration, temperature, pH, and floras were
      measured daily until the cords fell off. The results showed no difference between
      the groups in hydration, temperature, pH, and the colonization of floras, but
      cord detachment in the alcohol group took 2 days longer (12.8 [5.7] days) than in
      the water group (10.9 [4.1] days). Our findings suggest that the clean-and-dry
      method of cord care, which uses water, could be sufficient, possibly even better
      than alcohol in maintaining the physiologic surface milieu of the cord area with
      less chance of infection and manipulation in NICUs with optimal infection
      control. 

PMID- 24092870
TI  - Service characteristics as predictors of parents' perceptions of child
      rehabilitation outcomes.
AB  - Medical rehabilitation arranged by the Social Insurance Institution of Finland is
      provided for children with severe disabilities. The study aimed to find out which
      service characteristics were associated with perceived outcomes of
      rehabilitation. Parents whose children had participated in rehabilitation (n =
      496) responded to a mail questionnaire that included questions on service
      characteristics and possible outcomes. Based on factor analysis, four outcome
      variables were formed. Logistic regression analysis was used to identify the
      particular service characteristics that were associated with the perceived
      outcomes. The family's participation in rehabilitation planning and the child's
      willingness to participate in rehabilitation activities were associated with good
      outcomes. Having a contact person for the rehabilitation process predicted child
      and family empowerment outcomes. The results emphasize the significance of
      establishing a good partnership between the professionals and the family; of
      developing the contents of the rehabilitation program, so that they motivate the
      child, and of organizing service coordinators for each family. 

PMID- 24092871
TI  - A meta-analysis of the effect of school-based anti-bullying programs.
AB  - Bullying is a serious public health problem, and many studies have examined the
      effect of school-based anti-bullying programs. However, these programs and those
      outcomes are complex, broad, and diverse. Research is needed into the optimal
      strategies for these comprehensive programs, which consider both the
      effectiveness and cost of programs. We performed a meta-analysis of 13 studies
      using the Comprehensive Meta-Analysis software package to calculate effect size
      (ES) and the Q statistic. We conducted subgroup analyses to examine the
      differences based on student grade level, program duration, and program strategy.
      The pooled ES calculation indicated that school-based anti-bullying programs have
      a small to moderate effect on victimization. The results of the Q test indicated
      significant heterogeneity across studies of victimization (Q = 39.625; I (2) =
      69.7%; p < .001). Studies involving training in emotional control (p < .01), peer
      counseling (p < .05), or the establishment of a school policy on bullying (p <
      .05) showed significantly larger ESs on victimization than did studies that did
      not involve these strategies. Effective school-based anti-bullying programs
      should include training in emotional control, peer counseling, and the
      establishment of a school policy on bullying.

PMID- 24092872
TI  - The comparative effectiveness of prednisolone and dexamethasone for children with
      croup: a community-based randomized trial.
AB  - Background. Although common practice, evidence to support treatment of croup with
      prednisolone is scant. Methods. We conducted a community-based randomized trial
      to compare the effectiveness of prednisolone (2 mg/kg/d for 3 days, n = 41)
      versus 1 dose of dexamethasone (0.6 mg/kg) and 2 doses of placebo (n = 46).
      Participants were children 1 to 8 years old with croup symptoms <=48 hours,
      categorized as mild (42%) or moderate (58%). Results. There were no differences
      for those treated with dexamethasone or prednisolone for additional health care
      for croup (2% vs 7%, P = .34), duration of croup symptoms (2.8 vs 2.2 days, P =
      .63), nonbarky cough (6.1 vs 5.9 days, P = .81), nights with disturbed sleep for
      the parent (0.68 vs 1.21 nights, P = .55), and days with stress (1.39 vs 1.56
      days, P = .51). Conclusion. There were no detected differences in outcomes
      between the 2 croup treatments for either child or parent. 

PMID- 24092874
TI  - Skeletal muscle morphology and risk of cardiovascular disease in elderly men.
AB  - BACKGROUND: While it is well known that physical inactivity is a major risk
      factor for cardiovascular disease, there is still a search for the mechanisms by
      which exercise exerts its positive effect. Skeletal muscle fibre type can be
      affected to some extent by exercise, and different fibre types possess different
      anti-inflammatory and glucometabolic properties that may influence cardiovascular
      disease risk. DESIGN: Population-based cohort study. METHODS: We investigated
      relations of skeletal muscle morphology to risk of cardiovascular events in a
      sample of 466 71-year-old men without cardiovascular disease, of which 295 were
      physically active (strenuous physical activity at least 3 h/week). RESULTS:
      During a median of 13.1 years of follow up, 173 major cardiovascular events
      occurred. Among physically active men, 10% higher proportion of type-I (slow
      twitch oxidative) fibres was associated with a hazard ratio (HR) of 0.84 (95%
      confidence interval 0.74-0.95) for cardiovascular events, and 10% higher
      proportion of type-IIx (fast-twitch glycolytic) fibres was associated with a HR
      of 1.24 (1.06-1.45), adjusting for age. Similar results were observed in several
      sets of multivariable-adjusted models. No association of muscle fibre type with
      risk of cardiovascular events was observed among physically inactive men.
      CONCLUSIONS: Higher skeletal muscle proportion of type-I fibres was associated
      with lower risk of cardiovascular events and a higher proportion of type-IIx
      fibres was associated with higher risk of cardiovascular events. These relations
      were only observed in physically active men. Skeletal muscle fibre composition
      may be a mediator of the protective effects of exercise against cardiovascular
      disease.

PMID- 24092875
TI  - Reclassification of European patients' cardiovascular risk using the updated
      Systematic Coronary Risk Evaluation algorithm.
AB  - Data from the European Study on Cardiovascular Risk Prevention and Management in
      Usual Daily Practice (EURIKA; ClinicalTrials.gov; NCT00882336) was used to assess
      the proportions of patients aged 50-65 years free of diabetes and not receiving
      lipid-lowering therapy (LLT) considered to be at low (<1%), intermediate (1% to
      <5%) and high (>=5%) 10-year risk of cardiovascular mortality according to the
      Systematic Coronary Risk Evaluation (SCORE) algorithm and the updated algorithm
      that considers patients' total cholesterol and high-density lipoprotein
      cholesterol (HDL-C) levels as independent variables (SCORE-HDL). Of 2321 patients
      analysed, 19.3%, 60.7% and 20.0% were considered to be at low, intermediate and
      high cardiovascular risk respectively according to SCORE, and 25.7%, 57.2% and
      17.1% respectively according to SCORE-HDL. Thus, there was an overall trend
      towards reclassification from higher to lower risk categories when SCORE-HDL was
      compared with SCORE. 

PMID- 24092857
TI  - Recent advances in understanding enteric pathogenic Escherichia coli.
AB  - Although Escherichia coli can be an innocuous resident of the gastrointestinal
      tract, it also has the pathogenic capacity to cause significant diarrheal and
      extraintestinal diseases. Pathogenic variants of E. coli (pathovars or
      pathotypes) cause much morbidity and mortality worldwide. Consequently,
      pathogenic E. coli is widely studied in humans, animals, food, and the
      environment. While there are many common features that these pathotypes employ to
      colonize the intestinal mucosa and cause disease, the course, onset, and
      complications vary significantly. Outbreaks are common in developed and
      developing countries, and they sometimes have fatal consequences. Many of these
      pathotypes are a major public health concern as they have low infectious doses
      and are transmitted through ubiquitous mediums, including food and water. The
      seriousness of pathogenic E. coli is exemplified by dedicated national and
      international surveillance programs that monitor and track outbreaks;
      unfortunately, this surveillance is often lacking in developing countries. While
      not all pathotypes carry the same public health profile, they all carry an
      enormous potential to cause disease and continue to present challenges to human
      health. This comprehensive review highlights recent advances in our understanding
      of the intestinal pathotypes of E. coli.

PMID- 24092877
TI  - Oncogenic mutations in adenomatous polyposis coli (Apc) activate mechanistic
      target of rapamycin complex 1 (mTORC1) in mice and zebrafish.
AB  - Truncating mutations in adenomatous polyposis coli (APC) are strongly linked to
      colorectal cancers. APC is a negative regulator of the Wnt pathway and
      constitutive Wnt activation mediated by enhanced Wnt-beta-catenin target gene
      activation is believed to be the predominant mechanism responsible for APC mutant
      phenotypes. However, recent evidence suggests that additional downstream
      effectors contribute to APC mutant phenotypes. We previously identified a
      mechanism in cultured human cells by which APC, acting through glycogen synthase
      kinase-3 (GSK-3), suppresses mTORC1, a nutrient sensor that regulates cell growth
      and proliferation. We hypothesized that truncating Apc mutations should activate
      mTORC1 in vivo and that mTORC1 plays an important role in Apc mutant phenotypes.
      We find that mTORC1 is strongly activated in apc mutant zebrafish and in
      intestinal polyps in Apc mutant mice. Furthermore, mTORC1 activation is essential
      downstream of APC as mTORC1 inhibition partially rescues Apc mutant phenotypes
      including early lethality, reduced circulation and liver hyperplasia.
      Importantly, combining mTORC1 and Wnt inhibition rescues defects in morphogenesis
      of the anterior-posterior axis that are not rescued by inhibition of either
      pathway alone. These data establish mTORC1 as a crucial, beta-catenin independent
      effector of oncogenic Apc mutations and highlight the importance of mTORC1
      regulation by APC during embryonic development. Our findings also suggest a new
      model of colorectal cancer pathogenesis in which mTORC1 is activated in parallel
      with Wnt/beta-catenin signaling. 

PMID- 24092876
TI  - Mechanisms of skeletal muscle aging: insights from Drosophila and mammalian
      models.
AB  - A characteristic feature of aged humans and other mammals is the debilitating,
      progressive loss of skeletal muscle function and mass that is known as
      sarcopenia. Age-related muscle dysfunction occurs to an even greater extent
      during the relatively short lifespan of the fruit fly Drosophila melanogaster.
      Studies in model organisms indicate that sarcopenia is driven by a combination of
      muscle tissue extrinsic and intrinsic factors, and that it fundamentally differs
      from the rapid atrophy of muscles observed following disuse and fasting.
      Extrinsic changes in innervation, stem cell function and endocrine regulation of
      muscle homeostasis contribute to muscle aging. In addition, organelle dysfunction
      and compromised protein homeostasis are among the primary intrinsic causes. Some
      of these age-related changes can in turn contribute to the induction of
      compensatory stress responses that have a protective role during muscle aging. In
      this Review, we outline how studies in Drosophila and mammalian model organisms
      can each provide distinct advantages to facilitate the understanding of this
      complex multifactorial condition and how they can be used to identify suitable
      therapies. 

PMID- 24092878
TI  - Transcriptional changes and developmental abnormalities in a zebrafish model of
      myotonic dystrophy type 1.
AB  - Myotonic dystrophy type I (DM1) is a multi-system, autosomal dominant disorder
      caused by expansion of a CTG repeat sequence in the 3'UTR of the DMPK gene. The
      size of the repeat sequence correlates with age at onset and disease severity,
      with large repeats leading to congenital forms of DM1 associated with hypotonia
      and intellectual disability. In models of adult DM1, expanded CUG repeats lead to
      an RNA toxic gain of function, mediated at least in part by sequestering specific
      RNA splicing proteins, most notably muscleblind-related (MBNL) proteins. However,
      the impact of CUG RNA repeat expression on early developmental processes is not
      well understood. To better understand early developmental processes in DM1, we
      utilized the zebrafish, Danio rerio, as a model system. Direct injection of
      (CUG)91 repeat-containing mRNA into single-cell embryos induces toxicity in the
      nervous system and muscle during early development. These effects manifest as
      abnormal morphology, behavioral abnormalities and broad transcriptional changes,
      as shown by cDNA microarray analysis. Co-injection of zebrafish mbnl2 RNA
      suppresses (CUG)91 RNA toxicity and reverses the associated behavioral and
      transcriptional abnormalities. Taken together, these findings suggest that early
      expression of exogenously transcribed CUG repeat RNA can disrupt normal muscle
      and nervous system development and provides a new model for DM1 research that is
      amenable to small-molecule therapeutic development. 

PMID- 24092881
TI  - The involvement of beta-amyrin 28-oxidase (CYP716A52v2) in oleanane-type
      ginsenoside biosynthesis in Panax ginseng.
AB  - Panax species are the most popular medicinal herbs. The root of these plants
      contains pharmacologically active triterpene saponins, also known as
      ginsenosides, compounds that are divided into dammarane- and oleanane-type
      triterpenes. Two CYP716A subfamily genes (CYP716A47 and CYP716A53v2) were
      recently characterized, encoding an enzyme catalyzing the hydroxylation of
      dammarane-type triterpenes in Panax ginseng. Herein, we report that one CYP716A
      subfamily gene (CYP716A52v2) isolated from P. ginseng encodes a beta-amyrin 28
      oxidase, which is suggested to modify beta-amyrin into oleanolic acid, a
      precursor of an oleanane-type saponin (mainly ginsenoside Ro) in P. ginseng. The
      ectopic expression of both PNY1 and CYP716A52v2 in recombinant yeast resulted in
      erythrodiol and oleanolic acid production, respectively. In vitro enzymatic
      activity assays biochemically confirmed that CYP716A52v2 catalyzed the oxidation
      of beta-amyrin to produce oleanolic acid, and the chemical structure of the
      oleanolic acid product was confirmed using gas chromatography-mass spectrometry
      (GC/MS). Transgenic P. ginseng plants were generated via Agrobacterium
      tumefaciens-mediated transformation: the overexpression of CYP716A52v2 greatly
      increased the content of oleanane-type ginsenoside (ginsenoside Ro), whereas RNA
      interference against CYP716A52v2 markedly reduced it. Furthermore, the levels of
      other dammarene-type ginsenosides were not affected in these transgenic lines.
      These results indicate that CYP716A52v2 is a beta-amyrin 28-oxidase that plays a
      key role in the biosynthesis of oleanane-type triterpenes in P. ginseng.

PMID- 24092879
TI  - TGF-beta3 modulates the inflammatory environment and reduces scar formation
      following vocal fold mucosal injury in rats.
AB  - Transforming growth factor (TGF)-beta1 and TGF-beta3 have been reported to exert
      differential effects on wound healing, and possibly even account for tissue
      specific differences in scar formation. Scarring is particularly detrimental in
      the vocal fold mucosa (VFM), where destruction of the native extracellular matrix
      causes irreparable biomechanical changes and voice impairment. Here, in a series
      of in vitro and in vivo experiments, we identified differences in TGF-beta1 and
      TGF-beta3 transcription and immunolocalization to various cell subpopulations in
      naive and injured rat VFM, compared with oral mucosa (which undergoes rapid
      healing with minimal scar) and skin (which typically heals with scar). Treatment
      of cultured human vocal fold fibroblasts with TGF-beta3 resulted in less potent
      induction of profibrotic gene transcription, extracellular matrix synthesis and
      fibroblast-myofibroblast differentiation, compared with treatment with TGF-beta1
      and TGF-beta2. Finally, delivery of exogenous TGF-beta3 to rat VFM during the
      acute injury phase modulated the early inflammatory environment and reduced
      eventual scar formation. These experiments show that the TGF-beta isoforms have
      distinct roles in VFM maintenance and repair, and that TGF-beta3 redirects wound
      healing to improve VFM scar outcomes in vivo. 

PMID- 24092880
TI  - A new zebrafish model produced by TILLING of SOD1-related amyotrophic lateral
      sclerosis replicates key features of the disease and represents a tool for in
      vivo therapeutic screening.
AB  - Mutations in the superoxide dismutase gene (SOD1) are one cause of familial
      amyotrophic lateral sclerosis [ALS; also known as motor neuron disease (MND)] in
      humans. ALS is a relentlessly progressive neurodegenerative disease and, to date,
      there are no neuroprotective therapies with significant impact on the disease
      course. Current transgenic murine models of the disease, which overexpress mutant
      SOD1, have so far been ineffective in the identification of new therapies
      beneficial in the human disease. Because the human and the zebrafish (Danio
      rerio) SOD1 protein share 76% identity, TILLING ('targeting induced local lesions
      in genomes') was carried out in collaboration with the Sanger Institute in order
      to identify mutations in the zebrafish sod1 gene. A T70I mutant zebrafish line
      was characterised using oxidative stress assays, neuromuscular junction (NMJ)
      analysis and motor function studies. The T70I sod1 zebrafish model offers the
      advantage over current murine models of expressing the mutant Sod1 protein at a
      physiological level, as occurs in humans with ALS. The T70I sod1 zebrafish
      demonstrates key features of ALS: an early NMJ phenotype, susceptibility to
      oxidative stress and an adult-onset motor neuron disease phenotype. We have
      demonstrated that the susceptibility of T70I sod1 embryos to oxidative stress can
      be used in a drug screening assay, to identify compounds that merit further
      investigation as potential therapies for ALS. 

PMID- 24092882
TI  - Maize membrane-bound transcription factor Zmbzip17 is a key regulator in the
      cross-talk of ER quality control and ABA signaling.
AB  - Abiotic stresses disrupt protein folding and induce endoplasmic reticulum (ER)
      stress, which in turn activates the unfolded protein response (UPR) to aid in the
      refolding or degradation of misfolded proteins. The phytohormone ABA regulates
      many aspects of plant development and plays a central role in the stress
      response; however, the role of ABA in transducing stress signals to activate the
      UPR has not been recognized. In this study, a gene encoding the maize ortholog of
      AtbZIP17, a transmembrane transcription factor functioning as an ER stress
      transducer, was identified from the MaizeGDB database, and designated ZmbZIP17.
      ZmbZIP17 was induced by both ABA and ER stress-eliciting agents such as
      dithiotreitol (DTT) and tunicamycin (TM). Transiently expressed yellow
      fluorescent protein (YFP)-ZmbZIP17 co-localized with the ER marker HDEL-mCherry
      under control conditions, but partially translocated into the nucleus upon TM
      treatment or removal of the transmembrane domain. TM-induced processing of
      ZmbZIP17 was confirmed by Western blot analysis. When overexpressed in
      Arabidopsis, ZmbZIP17 triggered ER stress response gene expression and tolerance
      to DTT and TM, elevated ABA-responsive gene expression and ABA sensitivity both
      pre- and post-germination. Additionally, ABA was found to induce ER stress
      response gene expression, alone or synergistically with ZmbZIP17, in the absence
      of DTT or TM; while ZmbZIP17 was capable of interacting with ABA-responsive cis
      elements (ABREs) that exist in promoters of known ABA-responsive genes. Together,
      our results reveal a direct link between ER stress and ABA signaling pathways
      involving the ZmbZIP17 transcription factor.

PMID- 24092884
TI  - The Plant Organelles Database 3 (PODB3) update 2014: integrating electron
      micrographs and new options for plant organelle research.
AB  - The Plant Organelles Database 2 (PODB2), which was first launched in 2006 as
      PODB, provides static image and movie data of plant organelles, protocols for
      plant organelle research and external links to relevant websites. PODB2 has
      facilitated plant organellar research and the understanding of plant organelle
      dynamics. To provide comprehensive information on plant organelles in more
      detail, PODB2 was updated to PODB3 (http://podb.nibb.ac.jp/Organellome/). PODB3
      contains two additional components: the electron micrograph database and the
      perceptive organelles database. Through the electron micrograph database, users
      can examine the subcellular and/or suborganellar structures in various organs of
      wild-type and mutant plants. The perceptive organelles database provides
      information on organelle dynamics in response to external stimuli. In addition to
      the extra components, the user interface for access has been enhanced in PODB3.
      The data in PODB3 are directly submitted by plant researchers and can be freely
      downloaded for use in further analysis. PODB3 contains all the information
      included in PODB2, and the volume of data and protocols deposited in PODB3
      continue to grow steadily. We welcome contributions of data from all plant
      researchers to enhance the utility and comprehensiveness of PODB3. 

PMID- 24092883
TI  - Nucleotide pyrophosphatase/phosphodiesterase 1 exerts a negative effect on starch
      accumulation and growth in rice seedlings under high temperature and CO2
      concentration conditions.
AB  - Nucleotide pyrophosphatase/phosphodiesterase (NPP) is a widely distributed
      enzymatic activity occurring in both plants and mammals that catalyzes the
      hydrolytic breakdown of the pyrophosphate and phosphodiester bonds of a number of
      nucleotides. Unlike mammalian NPPs, the physiological function of plant NPPs
      remains largely unknown. Using a complete rice NPP1-encoding cDNA as a probe, in
      this work we have screened a rice shoot cDNA library and obtained complete cDNAs
      corresponding to six NPP genes (NPP1-NPP6). As a first step to clarify the role
      of NPPs, recombinant NPP1, NPP2 and NPP6 were purified from transgenic rice cells
      constitutively expressing NPP1, NPP2 and NPP6, respectively, and their enzymatic
      properties were characterized. NPP1 and NPP6 exhibited hydrolytic activities
      toward ATP, UDP-glucose and the starch precursor molecule, ADP-glucose, whereas
      NPP2 did not recognize nucleotide sugars as substrates, but hydrolyzed UDP, ADP
      and adenosine 5'-phosphosulfate. To gain insight into the physiological function
      of rice NPP1, an npp1 knockout mutant was characterized. The ADP-glucose
      hydrolytic activities in shoots of npp1 rice seedlings were 8% of those of the
      wild type (WT), thus indicating that NPP1 is a major determinant of ADP-glucose
      hydrolytic activity in rice shoots. Importantly, when seedlings were cultured at
      160 Pa CO2 under a 28 degrees C/23 degrees C (12 h light/12 h dark) regime, npp1
      shoots and roots were larger than those of wild-type (WT) seedlings. Furthermore,
      the starch content in the npp1 shoots was higher than that of WT shoots. Growth
      and starch accumulation were also enhanced under an atmospheric CO2 concentration
      (40 Pa) when plants were cultured under a 33 degrees C/28 degrees C regime. The
      overall data strongly indicate that NPP1 exerts a negative effect on plant growth
      and starch accumulation in shoots, especially under high CO2 concentration and
      high temperature conditions. 

PMID- 24092885
TI  - Authors' response: surgical outcomes after epiretinal membrane peeling combined
      with cataract surgery.

PMID- 24092887
TI  - Pharmacokinetics, clinical indications, and resistance mechanisms in molecular
      targeted therapies in cancer.
AB  - The strategy for discovery and development of new cancer drugs has shifted the
      field from cytotoxic agents to therapies that selectively target oncogenic
      drivers. In the last decade, a number of targeted cancer therapies have been
      discovered and proven effective in a variety of hematological and solid
      malignancies. In this article, we review clinical pharmacokinetic characteristics
      of the U.S. Food and Drug Administration-approved targeted therapies and provide
      an overview of key clinical trials that led to approval of these drugs. The major
      limiting factor of targeted treatment is the development of resistance. We
      describe general principles of resistance and specific, clinically confirmed
      mechanisms of resistance to several therapies in different malignancies. 

PMID- 24092886
TI  - Developing Behavioral Theory With the Systematic Integration of Community Social
      Capital Concepts.
AB  - Health behavior theories state that social environments influence health
      behaviors, but theories of how this occurs are relatively underdeveloped. This
      article systematically surveys community social capital concepts in health
      behavior literature and proposes a conceptual framework that integrates these
      concepts into existing behavioral theory. Fifty-three studies tested associations
      between community social capital concepts and physical activity (38 studies),
      smoking (19 studies), and diet (2 studies). Trustworthiness of community members
      was consistently associated with more health-promoting and less disease-promoting
      behaviors in 19 studies. Neighborly reciprocity showed mixed results in 10
      studies. Reporting a good sense of community was associated with more physical
      activity in only 5 of 16 studies. Neighborhood collective efficacy, which
      includes social cohesion and informal social control, was inconsistently
      associated with behaviors in 22 studies. Behavioral social norms were associated
      with smoking and physical activity in 2 of 6 studies, and neighborhood modeling
      of physical activity was associated with increased activity in 12 of 17 studies,
      with 1 opposing result. This review identifies several community social capital
      related concepts that are, at times, associated with both health-promoting and
      disease-promoting behaviors and often have no associations. Theory explains these
      findings by describing the relationships and interactions among these concepts.
      Using these findings, this article proposes a conceptual framework that
      integrates community social capital concepts into existing behavioral theory.
      Iterative empirically based theory development is needed to address these
      concepts, which affect behaviors. These results can also inform theoretically
      based community-based and socially tailored interventions. 

PMID- 24092889
TI  - A review of the specificity of exercises designed for conditioning the lumbar
      extensors.
AB  - OBJECTIVE: To review the specificity of exercises designed to condition the
      lumbar extensor musculature (ie, lumbar erector spinae and multifidus). METHODS:
      A review of studies examining effects of exercises designed to condition the
      lumbar extensors was conducted. Included were studies that examined the acute
      activation and chronic adaptation of the lumbar extensor musculature in response
      to benches and roman chair trunk extensions, free weights exercises (ie,
      deadlifts, squats, good-mornings, etc), floor and stability ball exercise (ie,
      trunk extensions, bridging, four-point kneeling, etc) and resistance machines
      (ie, those with and without pelvic restraints). RESULTS: Evidence suggests that
      the reviewed exercises designed to condition the lumbar extensors all may result
      in significant activation of this musculature during their performance. However,
      examination of training studies shows that for benches and roman chair trunk
      extensions, free weights exercises, floor and stability ball exercise and
      resistance machines without appropriate pelvic restraints, evidence suggests that
      they may be less effective for inducing chronic adaptations in the lumbar
      extensors as a result of their performance. Contrastingly, resistance machines
      that employ appropriate pelvic restraint to isolate lumbar extension are better
      evidenced to confer specific adaptations to the lumbar extensors. CONCLUSIONS:
      Numerous exercise approaches have been designed with the intention of
      conditioning the lumbar extensors. Those examined appear to activate the lumbar
      extensors; however, the specificity of many of these exercises for producing
      chronic adaptations may be questionable, potentially due to the compound nature
      of them allowing involvement of other musculature such as the hip extensors. Many
      of the reviewed exercises offer potential to condition the lumbar extensors,
      however, isolation of lumbar extension through appropriate pelvic restraint
      appears important for optimising specific adaptations in the lumbar extensors.

PMID- 24092890
TI  - Neuro-Behcet disease presenting with acute psychosis in an adolescent.
AB  - Behcet disease is a systemic vasculitis of unknown etiology that can affect the
      neurologic system. Neuro-Behcet disease is not well defined in children and
      adolescents, and the diagnosis is difficult to make in this population as they
      often present with insufficient symptoms to meet diagnostic criteria. Psychiatric
      symptoms as the initial manifestation of neuro-Behcet disease has rarely been
      reported. We describe a 17-year-old boy who presented with acute psychosis and
      was subsequently diagnosed with neuro-Behcet disease. A rare combination of both
      cerebral venous thrombosis and parenchymal central nervous system involvement was
      identified by neuroimaging. Although treatment guidelines for neuro-Behcet
      disease are limited, the patient made demonstrative clinical and radiographic
      improvement with a combination of corticosteroids, anticoagulation, and
      immunosuppressants, including a tumor necrosis factor-alpha (TNFalpha) blocking
      agent. 

PMID- 24092888
TI  - GALACTURONOSYLTRANSFERASE-LIKE5 is involved in the production of Arabidopsis seed
      coat mucilage.
AB  - The function of a putative galacturonosyltransferase from Arabidopsis
      (Arabidopsis thaliana; At1g02720; GALACTURONOSYLTRANSFERASE-LIKE5 [AtGATL5]) was
      studied using a combination of molecular genetic, chemical, and immunological
      approaches. AtGATL5 is expressed in all plant tissues, with highest expression
      levels in siliques 7 DPA. Furthermore, its expression is positively regulated by
      several transcription factors that are known to regulate seed coat mucilage
      production. AtGATL5 is localized in both endoplasmic reticulum and Golgi, in
      comparison with marker proteins resident to these subcellular compartments. A
      transfer DNA insertion in the AtGATL5 gene generates seed coat epidermal cell
      defects both in mucilage synthesis and cell adhesion. Transformation of atgatl5-1
      mutants with the wild-type AtGATL5 gene results in the complementation of all
      morphological phenotypes. Compositional analyses of the mucilage isolated from
      the atgatl5-1 mutant demonstrated that galacturonic acid and rhamnose contents
      are decreased significantly in atgatl5-1 compared with wild-type mucilage. No
      changes in structure were observed between soluble mucilage isolated from wild
      type and mutant seeds, except that the molecular weight of the mutant mucilage
      increased 63% compared with that of the wild type. These data provide evidence
      that AtGATL5 might function in the regulation of the final size of the mucilage
      rhamnogalacturonan I. 

PMID- 24092891
TI  - Pachymeningitis in a young child responded to antitubercular therapy: a case
      report.
AB  - Pachymeningitis is a rare disease of diverse etiology mainly affecting the adult
      population. Only 4 pediatric cases have been reported till now. We report the
      youngest child with pachymeningitis from India. Our case responded very well to
      antitubercular therapy with near complete recovery. Antitubercular therapy can be
      considered in children from endemic countries with hypertrophic pachymeningitis
      before labeling their condition as idiopathic hypertrophic pachymeningitis. 

PMID- 24092892
TI  - Migraine equivalents in childhood.
AB  - Migraine equivalents are a group of periodic and paroxysmal neurologic diseases.
      Because headache is not a prominent symptom, the diagnosis might be challenging.
      The objective of the study was to evaluate the frequency and outcome of migraine
      equivalents. This was a retrospective study. We included benign paroxysmal
      torticollis of infancy, benign paroxysmal vertigo of infancy, abdominal migraine,
      cyclic vomiting, aura without migraine, and confusional migraine. We evaluated
      the frequency of events, treatment, and outcome. Out of 674 children with
      headache, 38 (5.6%) presented with migraine equivalents. Twenty-one were boys and
      the mean age was 6.1 years. Fifteen had abdominal migraine, 12 benign paroxysmal
      vertigo, 5 confusional migraine, 3 aura without migraine, 2 paroxysmal
      torticollis, and 1 cyclic vomiting. Prophylactic treatment was introduced in 23
      patients; 4 lost follow-up and 19 had significant improvement. We conclude that
      the correct diagnosis of migraine equivalents enables an effective treatment with
      an excellent outcome. 

PMID- 24092893
TI  - Guillain-Barre syndrome and Crohn disease: a case report.
AB  - Development of both Crohn disease and Guillain-Barre syndrome likely involves
      autoimmunity associated with excessive inflammatory cytokines. We treated a girl
      who developed Guillain-Barre syndrome during the course of Crohn disease.
      Although high-dose gamma-globulin therapy administered initially for Guillain
      Barre syndrome was ineffective, plasmapheresis ameliorated her acute neuropathic
      symptoms. Crohn disease was managed with Salazopyrin administration and enteral
      feeding. Chronic inflammation of the intestinal mucosa caused by Crohn disease
      can allow presentation of microbial intestinal antigens normally hidden from the
      immune system. Such presentation could incite an extraintestinal immune response
      on the basis of molecular mimicry, leading to activation of systemic autoimmunity
      against the nervous system. Accordingly, concurrence of Guillain-Barre syndrome
      and Crohn disease in our patient appeared to result from shared autoimmune
      mechanisms and systemic and local increases in cytokine concentrations. The
      patient also developed erythema nodosum and gall stones, relatively common
      complications of Crohn disease. However, Guillain-Barre syndrome is rare. 

PMID- 24092894
TI  - Anti-N-methyl-D-aspartate (NMDA) receptor encephalitis: an unusual cause of
      autistic regression in a toddler.
AB  - Anti N-methyl-d-aspartate (NMDA) receptor encephalitis in children is associated
      with psychiatric changes, seizures, and dyskinesias. We present the first report
      of autistic regression in a toddler caused by this entity. A 33-month-old boy
      presented with decreased appetite, irritability, and insomnia following an upper
      respiratory tract infection. Over the next few weeks he lost language and social
      skills, and abnormal movements of his hand developed. Within a month, this
      patient came to fit the diagnostic criteria for autistic spectrum disorder. Upon
      investigation, anti-NMDA receptor antibodies were found in the boy's
      cerebrospinal fluid. He was treated with intravenous immunoglobulins and
      steroids, resulting in reacquisition of language and social skills and resolution
      of movements. Our case emphasizes the significance of suspecting anti-NMDA
      receptor encephalitis as the cause of autistic regression, even in an age group
      where the diagnosis of autistic spectrum disorder is typically made, and
      especially when presentation follows a febrile illness. 

PMID- 24092895
TI  - Anti-glutamic Acid decarboxylase antibody associated limbic encephalitis in a
      child: expanding the spectrum of pediatric inflammatory brain diseases.
AB  - Anti-glutamic acid decarboxylase directed antibodies are a rare cause of
      autoimmune limbic encephalitis that is relatively resistant to immunotherapy.
      Here we report a 15-year-old boy with nonparaneoplastic, anti-glutamic acid
      decarboxylase limbic encephalitis presenting with subacute headache, memory
      disturbance, psychiatric symptoms, and seizures. At onset, his memory disturbance
      manifested as transient global amnesia-like episodes. Clinical remission was
      achieved with rituximab, intravenous immunoglobulin, and corticosteroids. 

PMID- 24092896
TI  - Clinical and magnetic resonance imaging (MRI) distinctions between tumefactive
      demyelination and brain tumors in children.
AB  - Tumefactive demyelinating lesions can be difficult to distinguish from tumors.
      Clinical and magnetic resonance imaging features of children with tumefactive
      demyelination and supratentorial brain tumors were compared. Patients were
      identified through a 23-site national demyelinating disease study, and from a
      single-site neuroradiology database. For inclusion, lesions met at least 1 of 3
      criteria: maximal cross-sectional diameter >20 mm, local or global cerebral mass
      effect, or presence of perilesional edema. Thirty-one children with tumefactive
      demyelination (5 with solitary lesions) were identified: 27 of 189 (14.3%) from
      the demyelinating disease study and 4 from the database. Thirty-three children
      with tumors were identified. Children with tumefactive demyelination were more
      likely to have an abnormal neurologic examination and polyfocal neurologic
      deficits compared to children with tumors. Tumefactive demyelination was
      distinguished from tumor by the presence of multiple lesions, absence of cortical
      involvement, and decrease in lesion size or detection of new lesions on serial
      imaging. 

PMID- 24092897
TI  - Pediatric-onset extracephalic stabbing pain.
AB  - Idiopathic stabbing headache is a primary headache defined as "transient stabs of
      pain in the head that occur spontaneously in the absence of underlying organic
      disease." Although its variant form, stabbing pain with extracephalic
      distribution, has been reported in rare adult cases, pediatric presentation is
      extremely rare. We report an 8-year-old boy suffering from severe stabbing pain
      in the left side of the chest, right side of the abdomen, and right knee lasting
      2 to 3 minutes with increasing frequency. He was completely normal between
      attacks. The attack was not accompanied with headache initially. Investigation
      showed no abnormality. A diagnosis of extracephalic stabbing pain was made. The
      patient's symptoms were ameliorated by administration of valproic acid. This
      report illustrates that extracephalic stabbing pain can occur in pediatric
      patients. It is important to be aware of this peculiar condition because the pain
      is so severe, and it can be treatable with medication.

PMID- 24092898
TI  - Salvage of a recurrent phalangeal non-union with bone defect using autologous
      platelet glue and corticocancellous bone graft.

PMID- 24092899
TI  - Direct access to physical therapy for patients with low back pain in the
      Netherlands: prevalence and predictors.
AB  - BACKGROUND: In the Netherlands, direct access to physical therapy was introduced
      in 2006. Although many patients with back pain visit physical therapists through
      direct access, the frequency and characteristics of episodes of care are unknown.
      OBJECTIVE: The purposes of this study were: (1) to investigate the prevalence of
      direct access to physical therapy for patients with low back pain in the
      Netherlands from 2006 to 2009, (2) to examine associations between mode of access
      (direct versus referral) and patient characteristics, and (3) to describe the
      severity of the back complaints at the beginning and end of treatment for direct
      access and referral-based physical therapy. DESIGN: A cross-sectional study was
      conducted using registration data of physical therapists obtained from a
      longitudinal study. METHOD: Data were used from the National Information Service
      for Allied Health Care, a registration network of Dutch physical therapists. Mode
      of access (direct or referral) was registered for each episode of physical
      therapy care due to back pain from 2006 to 2009. Logistic regression analysis was
      used to explore associations between mode of access and patient/clinical
      characteristics. RESULTS: The percentage of episodes of care for which patients
      with back pain directly accessed a physical therapist increased from 28.9% in
      2006 to 52.1% in 2009. Characteristics associated with direct access were: middle
      or higher education level (odds ratio [OR]=1.3 and 2.0, respectively), previous
      physical therapy care (OR=1.7), recurrent back pain (OR=1.7), duration of back
      pain <7 days (OR=4.2), and age >55 years (OR=0.6). LIMITATIONS: The study could
      not compare outcomes of physical therapy care by mode of access because this
      information was not registered from the beginning of data collection and,
      therefore, was missing for too many cases. CONCLUSIONS: Direct access was used
      for an increasing percentage of episodes of physical therapy care in the years
      2006 to 2009. Patient/clinical characteristics associated with the mode of access
      were education level, recurrent back pain, previous physical therapy sessions,
      and age.

PMID- 24092900
TI  - Increasing the clinical utility of the BESTest, mini-BESTest, and brief-BESTest:
      normative values in Canadian adults who are healthy and aged 50 years or older.
AB  - BACKGROUND: Balance is a composite ability requiring the integration of multiple
      systems. The Balance Evaluation Systems Test (BESTest) and 2 abbreviated versions
      (the Mini-BESTest and the Brief-BESTest) are balance assessment tools that target
      these systems. To date, no normative data exist for any version of the BESTest.
      OBJECTIVE: The purpose of this study was to determine the age-related normative
      scores on the BESTest, Mini-BESTest, and Brief-BESTest for Canadians who are
      healthy and 50 to 89 years of age. DESIGN: A cross-sectional study design was
      used. METHODS: Seventy-nine adults who were healthy and aged 50 to 89 years (mean
      age=68.9 years; 50.6% women) participated. Normative scores were reported by age
      decade. RESULTS: Mean BESTest scores were 95.7 (95% confidence interval [CI]=94.4
      97.1) for adults who were aged 50 to 59 years, 91.4 (95% CI=89.8-93.0) for those
      who were aged 60 to 69 years, 85.4 (95% CI=82.5-88.2) for those who were aged 70
      to 79 years, and 79.4 (95% CI=74.3-84.5) for those who were aged 80 to 89 years.
      Similar results were obtained for the Mini-BESTest and the Brief-BESTest, and all
      3 tests showed statistically significant differences in scores among the age
      cohorts. LIMITATIONS: Because only adults who were 50 to 89 years of age were
      tested, there are still no normative data for people outside this age range.
      Also, the scores presented may not be generalizable to all countries.
      CONCLUSIONS: These normative data enhance the clinical utility of the BESTest,
      Mini-BESTest, and Brief-BESTest by providing clinicians with reference points to
      guide treatment.

PMID- 24092901
TI  - Can progressive resistive exercise improve weight, limb girth, and strength of
      individuals with HIV disease?

PMID- 24092902
TI  - Health-enhancing physical activity in children with cerebral palsy: more of the
      same is not enough.
AB  - Physical activity is important for young people's health. The emphasis over the
      last 2 decades has been on moderate to vigorous exercise when designing activity
      and exercise programs for children and adolescents with cerebral palsy (CP).
      Emerging evidence suggests that sedentary behavior is distinctly different from a
      lack of moderate to vigorous physical activity and has independent and different
      physiological mechanisms. The concept of concurrently increasing moderate to
      vigorous physical activity and replacing sedentary behavior with light physical
      activity may be beneficial for children and adolescents with CP. This article is
      a summary of the evidence for what works and what does not work for improving the
      physical activity of children and adolescents with CP. It also discusses what is
      known about sedentary behavior of children and adolescents with CP and what
      research directions are needed to build foundational knowledge in this area with
      this population. 

PMID- 24092903
TI  - Interrater reliability of the Berg Balance Scale when used by clinicians of
      various experience levels to assess people with lower limb amputations.
AB  - BACKGROUND: People with lower limb amputations frequently have impaired balance
      ability. The Berg Balance Scale (BBS) has excellent psychometric properties for
      people with neurologic disorders and elderly people dwelling in the community. A
      Rasch analysis demonstrated the validity of the BBS for people with lower limb
      amputations of all ability strata, but rater reliability has not been tested.
      OBJECTIVE: The study objective was to determine the interrater reliability and
      intrarater reliability of BBS scores and the differences in scores assigned by
      testers with various levels of experience when assessing people with lower limb
      amputations. DESIGN: This reliability study of video-recorded single-session BBS
      assessments had a cross-sectional design. METHODS: From a larger study of people
      with lower limb amputations, 5 consecutively recruited participants using
      prostheses were video recorded during an in-person BBS assessment. Sixteen
      testers independently rated the video-recorded assessments. Testers were 3
      physical therapists, 1 occupational therapist, 3 third-year and 4 second-year
      doctor of physical therapy (DPT) students, and 5 first-year DPT students without
      clinical training. Rater reliability was calculated using intraclass correlation
      coefficients (ICC [2,k]). Differences in scores assigned by testers with various
      levels of experience were determined by use of an analysis of variance with Tukey
      post hoc tests. RESULTS: The average age of the participants was 53.0 years
      (SD=15.7). Amputations had occurred at the ankle disarticulation, transtibial,
      and transfemoral levels because of vascular, trauma, and medical etiologies an
      average of 8.2 years earlier (SD=7.9). Berg Balance Scale scores spanned all
      ability strata. Interrater reliability (ICC [2,k]=.99) and intrarater reliability
      of scores determined in person and through video-recorded assessments by the same
      testers (ICC [2,k]=.99) were excellent. For participants with the lowest levels
      of ability, licensed professionals assigned lower scores than did DPT students
      without clinical training. LIMITATIONS: Intrarater reliability calculations were
      based on 2 testers. CONCLUSIONS: Berg Balance Scale scores assigned to people
      using prostheses by testers with various levels of clinical experience had
      excellent interrater reliability and intrarater reliability.

PMID- 24092904
TI  - The Groningen Meander Walking Test: a dynamic walking test for older adults with
      dementia.
AB  - BACKGROUND: Current dynamic walking tests, used in studies with older adults with
      dementia, rely strongly on healthy cognitive and physical function. Therefore,
      the Groningen Meander Walking Test (GMWT) was developed specifically for people
      with dementia. The aim of the GMWT is to measure dynamic walking ability by
      walking over a meandering curved line, with an emphasis on walking speed and
      stepping accuracy, while changing direction. OBJECTIVE: The purpose of this study
      was to investigate the feasibility, test-retest reliability, and minimal
      detectable change (MDC) of the GMWT. DESIGN: A repeated-measures design was used.
      METHODS: Forty-two people with dementia participated in the study. Adherence
      rate, adverse events, repetition of instructions during test performance, test
      duration, and number of oversteps were assessed. RESULTS: The adherence rate was
      excellent, with no adverse events. No repetitive instructions were given during
      test performance, and test duration was short (mean=17.16 seconds) with few
      oversteps (mean=1.94 oversteps). Test-retest reliability for participants without
      a walking device was excellent for the GMWT time score (intraclass correlation
      coefficient [ICC]=.942), with an MDC of 2.96 seconds. Test-retest reliability for
      participants with a 4-wheeled walker (4WW) was moderate (ICC=.837), with an MDC
      of 10.35 seconds. For the overstep score, a marginal ICC of .630 was found, with
      an MDC of 4.38 oversteps. LIMITATIONS: No fall data were available, and there was
      a volunteer bias. CONCLUSIONS: The GMWT is a feasible test for people with
      dementia. With the GMWT time score, a reliable and sensitive field test to
      measure walking abilities in older adults with dementia is available. The GMWT
      overstep score can be used to give information about the execution according to
      protocol and should be emphasized during the instructions. Future studies need to
      investigate the validity of the GMWT.

PMID- 24092905
TI  - Global position sensing and step activity as outcome measures of community
      mobility and social interaction for an individual with a transfemoral amputation
      due to dysvascular disease.
AB  - BACKGROUND AND PURPOSE: Community mobility of individuals following lower limb
      amputation is highly variable and has a great impact on their quality of life.
      Currently, clinical assessments of ambulatory ability and motivation influence
      prosthetic prescription. However, these outcome measures do not effectively
      quantify community mobility (ie, mobility outside of the clinic) of individuals
      with an amputation. Advances in global positioning systems (GPSs) and other
      wearable step-monitoring devices allow for objective, quantifiable measurement of
      community mobility. This case report will examine the combined use of a GPS unit
      and a step activity monitor to quantify community mobility and social interaction
      of an individual with transfemoral amputation due to dysvascular disease. CASE
      DESCRIPTION: A 76-year-old woman with a unilateral transfemoral amputation due to
      vascular disease carried a commercial GPS unit and step activity monitor to
      quantify her community mobility and social interaction every day over a period of
      1 month. The step activity monitor was affixed to her prosthesis. The patient
      used a wheelchair as well as her prosthesis for everyday mobility. OUTCOME:
      Information from the GPS unit and step activity monitor provided quantitative
      details on the patient's steps taken in and out of the home, wheelchair use,
      prosthesis use, driving trips, and time spent on social and community trips.
      DISCUSSION: This case report describes a potential clinical measurement procedure
      for quantifying community mobility and social interaction of an individual with
      lower limb amputation. Future efforts are needed to validate this measurement
      tool on large sample sizes and in individuals with different mobility levels.
      Additionally, automatization of data analysis and technological approaches to
      reduce compromised GPS signals may eventually lead to a practical, clinically
      useful tool.

PMID- 24092906
TI  - Safety checklist compliance and a false sense of safety: new directions for
      research.

PMID- 24092908
TI  - Declining genital Warts in young women in england associated with HPV 16/18
      vaccination: an ecological study.
AB  - BACKGROUND: Diagnoses of genital warts (GW) in genitourinary medicine (GUM)
      clinics have been increasing in England for many years. In 2008, an HPV
      immunization program began with a bivalent vaccine (Cervarix). This was expected
      to markedly reduce infections and disease due to human papillomavirus (HPV) 16/18
      but not HPV 6/11 infections or disease. However, from 2009 to 2011 there were
      decreases in reported diagnoses of GW in young females at GUM clinics. METHODS:
      Using data from GUM clinics and a sample of general practices (GPs) throughout
      England, we analyzed rates of GW diagnoses by age, year of diagnosis, and
      estimated immunization coverage. RESULTS: The overall reduction in GW diagnoses
      at GUM clinics between 2008 and 2011 was 13.3% among 16- to 19-year-old females,
      with the greatest decline of 20.8% in 17-year-olds. Declines were positively
      associated with estimated immunization coverage. A similar pattern was seen in GP
      diagnoses, but not among older women, and for other GUM consultations.
      CONCLUSIONS: Several factors might contribute to declines in GW. However, the
      size and pattern of the declines strongly suggest that we are observing an
      unexpected, moderately protective effect of HPV 16/18 vaccination against GW.

PMID- 24092907
TI  - Efficacy of the HPV-16/18 AS04-adjuvanted vaccine against low-risk HPV types
      (PATRICIA randomized trial): an unexpected observation.
AB  - BACKGROUND: Public Health England has reported a decrease of up to 20.8% in new
      diagnoses of external genital warts (GWs) among women aged <19 years since the
      national vaccination program with the human papillomavirus (HPV)-16/18 AS04
      adjuvanted vaccine began in 2008. A post hoc analysis of the phase III PATRICIA
      (PApilloma TRIal against Cancer In young Adults) trial (NCT00122681) was
      performed to ascertain whether protection against low-risk HPV types was
      apparent. METHODS: Vaccine efficacy (VE) at 48 months was assessed against 6
      month persistent infection (6MPI) with low-risk HPV types in the total vaccinated
      cohort (TVC) and in the TVC naive (for 25 HPV types tested) populations. RESULTS:
      In the TVC naive cohort, VE against 6MPI (95% confidence interval) was 34.5%
      (11.3 to 51.8) for HPV-6/11, 34.9% (9.1 to 53.7) for HPV-6, 30.3% (-45.0 to 67.5)
      for HPV-11, and 49.5% (21.0 to 68.3) for HPV-74. CONCLUSIONS: The HPV-16/18 AS04
      adjuvanted vaccine appears to have moderate efficacy against persistent
      infections with a number of low-risk HPV types (HPV-6/11/74), which are
      responsible for the majority of external GWs, and recently, antibody and cell
      mediated immune response to HPV-6/11 have been observed. These findings may help
      to explain the decrease in external GW diagnoses seen in England.

PMID- 24092915
TI  - The elevation of apoB in hypercholesterolemic patients is primarily attributed to
      the relative increase of apoB/Lp-PLA2.
AB  - Lipoprotein-associated phospholipase A2 (Lp-PLA2) is a risk factor of
      cardiovascular disease. Plasma Lp-PLA2 is mainly associated with apolipoprotein
      (apo)B-containing lipoproteins, primarily with low density lipoproteins (LDLs).
      Importantly, only a proportion of circulating lipoproteins contain Lp-PLA2. We
      determined the plasma levels of Lp-PLA2-bound apoB (apoB/Lp-PLA2) in patients
      with primary hypercholesterolemia. The effect of simvastatin therapy was also
      addressed. The plasma apoB/Lp-PLA2 concentration in 50 normolipidemic controls
      and 53 patients with primary hypercholesterolemia at baseline and at 3 months
      posttreatment with simvastatin (40 mg/day) was determined by an enzyme-linked
      immunosorbent assay. The concentration of the apoB-containing lipoproteins that
      do not bind Lp-PLA2 [apoB/Lp-PLA2-] was calculated by subtracting the apoB/Lp
      PLA2 from total apoB. The apoB/Lp-PLA2 levels were 3.6-fold higher, while apoB/Lp
      PLA2- were 1.3-fold higher in patients compared with controls. After 3 months of
      simvastatin treatment apoB/Lp-PLA2 and apoB/Lp-PLA2- levels were reduced by 52%
      and 33%, respectively. The elevation in apoB-containing lipoproteins in
      hypercholesterolemic patients is mainly attributed to the relative increase in
      the proatherogenic apoB/Lp-PLA2, while simvastatin reduces these particles to a
      higher extent compared with apoB/Lp-PLA2-. Considering that Lp-PLA2 is
      proatherogenic, the predominance of apoB/Lp-PLA2 particles in
      hypercholesterolemic patients may contribute to their higher atherogenicity and
      incidence of cardiovascular disease.

PMID- 24092916
TI  - A Meta-Analysis of Interventions for Struggling Readers in Grades 4-12: 1980
      2011.
AB  - This meta-analysis synthesizes the literature on interventions for struggling
      readers in Grades 4 through 12 published between 1980 and 2011. It updates
      Scammacca et al.'s analysis of studies published between 1980 and 2004. The
      combined corpus of 82 study-wise effect sizes was meta-analyzed to determine (a)
      the overall effectiveness of reading interventions studied over the past 30
      years, (b) how the magnitude of the effect varies based on student, intervention,
      and research design characteristics, and (c) what differences in effectiveness
      exist between more recent interventions and older ones. The analysis yielded a
      mean effect of 0.49, considerably smaller than the 0.95 mean effect reported in
      2007. The mean effect for standardized measures was 0.21, also much smaller than
      the 0.42 mean effect reported in 2007. The mean effects for reading comprehension
      measures were similarly diminished. Results indicated that the mean effects for
      the 1980-2004 and 2005-2011 groups of studies were different to a statistically
      significant degree. The decline in effect sizes over time is attributed at least
      in part to increased use of standardized measures, more rigorous and complex
      research designs, differences in participant characteristics, and improvements in
      the school's "business-as-usual" instruction that often serves as the comparison
      condition in intervention studies. 

PMID- 24092917
TI  - A new face of Borjeson-Forssman-Lehmann syndrome? De novo mutations in PHF6 in
      seven females with a distinct phenotype.
AB  - BACKGROUND: Borjeson-Forssman-Lehmann syndrome (BFLS) is an X-linked recessive
      intellectual disability (ID) disorder caused by mutations in the PHF6 gene and
      characterised by variable cognitive impairment, a distinct facial gestalt,
      obesity, and hypogonadism. Female carriers are usually not affected or only
      mildly affected, and so far only two females with de novo mutations or deletions
      in PHF6 have been reported. METHODS AND RESULTS: We performed PHF6 mutational
      analysis and screening for intragenic deletions and duplications by quantitative
      real-time PCR and multiplex ligation dependent probe amplification (MLPA) in
      female patients with variable ID and a distinct appearance of sparse hair,
      remarkable facial features, hypoplastic nails, and teeth anomalies. We detected
      two truncating mutations and two duplications of exons 4 and 5. Furthermore, two
      female patients with PHF6 deletions and a similar phenotype were identified by
      routine molecular karyotyping. Recently, two patients with a clinical diagnosis
      of Coffin-Siris syndrome in early infancy had been found to harbour mutations in
      PHF6, and their phenotype in advanced ages is now described. Further studies
      revealed skewed X-inactivation in blood lymphocytes, while it was normal in
      fibroblasts, thus indicating functional mosaicism. CONCLUSIONS: Our findings
      indicate that de novo defects in PHF6 in females result in a recognisable
      phenotype which might have been under-recognised so far and which comprises
      variable ID, a characteristic facial gestalt, hypoplastic nails, brachydactyly,
      clinodactyly mainly of fingers IV and V, dental anomalies, and linear skin
      hyperpigmentation. It shows overlap with BFLS but also additional distinct
      features, thus adding a new facet to this disorder.

PMID- 24092918
TI  - Prostate-specific antigen screening trials and prostate cancer deaths: the
      androgen deprivation connection.
AB  - Major clinical trials using prostate-specific antigen (PSA) as the screening test
      to detect localized early-stage prostate cancer and to attempt to change its
      natural history with early intervention have yielded conflicting interpretations.
      The US Prostate, Lung, Colorectal, and Ovarian (US PLCO) cancer screening trial
      concluded that PSA-based screening conferred no meaningful survival benefit,
      whereas the European Randomized Study of Screening for Prostate Cancer (ERSPC)
      and the GOTEBORG clinical trial (GOTEBORG) trials claimed statistically
      significant life-saving benefits. These divergent outcomes have not provided
      physicians with clarity on the best evidence-based treatment. To determine the
      extent to which these divergent outcomes are clinically meaningful, we evaluated
      these data and those of a long-term prospective cohort study in the context of
      the clinically documented harms of androgen deprivation therapy (ADT). We noted
      the unheralded fact that in both European trials far more patients received
      hormonal treatment in the control than the prostatectomy arm, whereas hormonal
      therapy in the US trial was balanced between arms. We examined this imbalance in
      ADT treatment and prostate cancer-related deaths in the contexts of
      contamination, stage migration, and attribution of cause of death, all of which
      impinge on data interpretation. The ERSPC and GOTEBORG data are compatible with
      the hypothesis that ADT treatment contributes differentially to an increase in
      prostate cancer deaths in control patients. If so, the claim of a reduction in
      prostate cancer deaths in the screened cohort requires reappraisal. The
      conventional interpretation that PSA screening and radical treatment intervention
      are the major contributors to the results of these two studies needs more
      rigorous scientific scrutiny, as does the role of ADT treatment of nonmetastatic
      disease. 

PMID- 24092919
TI  - Prostate cancer screening: biases and the need for consensus.

PMID- 24092920
TI  - Combating resistance to anti-IGFR antibody by targeting the integrin beta3-Src
      pathway.
AB  - BACKGROUND: Several phase II/III trials of anti-insulin-like growth factor 1
      receptor (IGF-1R) monoclonal antibodies (mAbs) have shown limited efficacy. The
      mechanisms of resistance to IGF-1R mAb-based therapies and clinically applicable
      strategies for overcoming drug resistance are still undefined. METHODS: IGF-1R
      mAb cixutumumab efficacy, alone or in combination with Src inhibitors, was
      evaluated in 10 human head and neck squamous cell carcinoma (HNSCC) and six non
      small cell lung cancer (NSCLC) cell lines in vitro in two- or three-dimensional
      culture systems and in vivo in cell line- or patient-derived xenograft tumors in
      athymic nude mice (n = 6-9 per group). Cixutumumab-induced changes in cell
      signaling and IGF-1 binding to integrin beta3 were determined by Western or
      ligand blotting, immunoprecipitation, immunofluorescence, and cell adhesion
      analyses and enzyme-linked immunosorbent assay. Data were analyzed by the two
      sided Student t test or one-way analysis of variance. RESULTS: Integrin beta3-Src
      signaling cascade was activated by IGF-1 in HNSCC and NSCLC cells, when IGF-1
      binding to IGF-1R was hampered by cixutumumab, resulting in Akt activation and
      cixutumumab resistance. Targeting integrin beta3 or Src enhanced antitumor
      activity of cixutumumab in multiple cixutumumab-resistant cell lines and patient
      derived tumors in vitro and in vivo. Mean tumor volume of mice cotreated with
      cixutumumab and integrin beta3 siRNA was 133.7 mm(3) (95% confidence interval
      [CI] = 57.6 to 209.8 mm(3)) compared with those treated with cixutumumab (1472.5
      mm(3); 95% CI = 1150.7 to 1794.3 mm(3); P < .001) or integrin beta3 siRNA (903.2
      mm(3); 95% CI = 636.1 to 1170.3 mm(3); P < .001) alone. CONCLUSIONS: Increased
      Src activation through integrin alphanubeta3 confers considerable resistance
      against anti-IGF-1R mAb-based therapies in HNSCC and NSCLC cells. Dual targeting
      of the IGF-1R pathway and collateral integrin beta3-Src signaling module may
      override this resistance.

PMID- 24092921
TI  - Ikaros' suspended flight in the thymus.

PMID- 24092922
TI  - Panobinostat to revert bortezomib resistance.

PMID- 24092923
TI  - SH2B3: a new leukemia predisposition gene.

PMID- 24092924
TI  - STAT3 mutations and persistence of autoimmunity.

PMID- 24092925
TI  - Kindlin ignites a new flame.

PMID- 24092926
TI  - Doubling down on PKC benefits allogeneic BMT.

PMID- 24092927
TI  - Leukocytes talking to VE-cadherin.

PMID- 24092928
TI  - Protection of glucagon-like peptide-1 in cisplatin-induced renal injury
      elucidates gut-kidney connection.
AB  - Accumulating evidence of the beyond-glucose lowering effects of a gut-released
      hormone, glucagon-like peptide-1 (GLP-1), has been reported in the context of
      remote organ connections of the cardiovascular system. Specifically, GLP-1
      appears to prevent apoptosis, and inhibition of dipeptidyl peptidase-4 (DPP-4),
      which cleaves GLP-1, is renoprotective in rodent ischemia-reperfusion injury
      models. Whether this renoprotection involves enhanced GLP-1 signaling is unclear,
      however, because DPP-4 cleaves other molecules as well. Thus, we investigated
      whether modulation of GLP-1 signaling attenuates cisplatin (CP)-induced AKI. Mice
      injected with 15 mg/kg CP had increased BUN and serum creatinine and CP caused
      remarkable pathologic renal injury, including tubular necrosis. Apoptosis was
      also detected in the tubular epithelial cells of CP-treated mice using
      immunoassays for single-stranded DNA and activated caspase-3. Treatment with a
      DPP-4 inhibitor, alogliptin (AG), significantly reduced CP-induced renal injury
      and reduced the renal mRNA expression ratios of Bax/Bcl-2 and Bim/Bcl-2. AG
      treatment increased the blood levels of GLP-1, but reversed the CP-induced
      increase in the levels of other DPP-4 substrates such as stromal cell-derived
      factor-1 and neuropeptide Y. Furthermore, the GLP-1 receptor agonist exendin-4
      reduced CP-induced renal injury and apoptosis, and suppression of renal GLP-1
      receptor expression in vivo by small interfering RNA reversed the renoprotective
      effects of AG. These data suggest that enhancing GLP-1 signaling ameliorates CP
      induced AKI via antiapoptotic effects and that this gut-kidney axis could be a
      new therapeutic target in AKI. 

PMID- 24092929
TI  - Obesity-mediated autophagy insufficiency exacerbates proteinuria-induced
      tubulointerstitial lesions.
AB  - Obesity is an independent risk factor for renal dysfunction in patients with
      CKDs, including diabetic nephropathy, but the mechanism underlying this
      connection remains unclear. Autophagy is an intracellular degradation system that
      maintains intracellular homeostasis by removing damaged proteins and organelles,
      and autophagy insufficiency is associated with the pathogenesis of obesity
      related diseases. We therefore examined the role of autophagy in obesity-mediated
      exacerbation of proteinuria-induced proximal tubular epithelial cell damage in
      mice and in human renal biopsy specimens. In nonobese mice, overt proteinuria,
      induced by intraperitoneal free fatty acid-albumin overload, led to mild tubular
      damage and apoptosis, and activated autophagy in proximal tubules reabsorbing
      urinary albumin. In contrast, diet-induced obesity suppressed proteinuria-induced
      autophagy and exacerbated proteinuria-induced tubular cell damage. Proximal
      tubule-specific autophagy-deficient mice, resulting from an Atg5 gene deletion,
      subjected to intraperitoneal free fatty acid-albumin overload developed severe
      proteinuria-induced tubular damage, suggesting that proteinuria-induced autophagy
      is renoprotective. Mammalian target of rapamycin (mTOR), a potent suppressor of
      autophagy, was activated in proximal tubules of obese mice, and treatment with an
      mTOR inhibitor ameliorated obesity-mediated autophagy insufficiency. Furthermore,
      both mTOR hyperactivation and autophagy suppression were observed in tubular
      cells of specimens obtained from obese patients with proteinuria. Thus, in
      addition to enhancing the understanding of obesity-related cell vulnerability in
      the kidneys, these results suggest that restoring the renoprotective action of
      autophagy in proximal tubules may improve renal outcomes in obese patients. 

PMID- 24092931
TI  - Proximal tubules forget "self-eating" when they meet Western meals.

PMID- 24092930
TI  - Cyclosporine induces endothelial cell release of complement-activating
      microparticles.
AB  - Defective control of the alternative pathway of complement is an important risk
      factor for several renal diseases, including atypical hemolytic uremic syndrome.
      Infections, drugs, pregnancy, and hemodynamic insults can trigger episodes of
      atypical hemolytic uremic syndrome in susceptible patients. Although the
      mechanisms linking these clinical events with disease flares are unknown, recent
      work has revealed that each of these clinical conditions causes cells to release
      microparticles. We hypothesized that microparticles released from injured
      endothelial cells promote intrarenal complement activation. Calcineurin
      inhibitors cause vascular and renal injury and can trigger hemolytic uremic
      syndrome. Here, we show that endothelial cells exposed to cyclosporine in vitro
      and in vivo release microparticles that activate the alternative pathway of
      complement. Cyclosporine-induced microparticles caused injury to bystander
      endothelial cells and are associated with complement-mediated injury of the
      kidneys and vasculature in cyclosporine-treated mice. Cyclosporine-induced
      microparticles did not bind factor H, an alternative pathway regulatory protein
      present in plasma, explaining their complement-activating phenotype. Finally, we
      found that in renal transplant patients, the number of endothelial microparticles
      in plasma increases 2 weeks after starting tacrolimus, and treatment with
      tacrolimus associated with increased C3 deposition on endothelial microparticles
      in the plasma of some patients. These results suggest that injury-associated
      release of endothelial microparticles is an important mechanism by which systemic
      insults trigger intravascular complement activation and complement-dependent
      renal diseases. 

PMID- 24092932
TI  - Inflammation, obesity, and thrombosis.
AB  - Clinical and epidemiological studies support a connection between obesity and
      thrombosis, involving elevated expression of the prothrombotic molecules
      plasminogen activator inhibitor-1 and tissue factor (TF) and increased platelet
      activation. Cardiovascular diseases and metabolic syndrome-associated disorders,
      including obesity, insulin resistance, type 2 diabetes, and hepatic steatosis,
      involve inflammation elicited by infiltration and activation of immune cells,
      particularly macrophages, into adipose tissue. Although TF has been clearly
      linked to a procoagulant state in obesity, emerging genetic and pharmacologic
      evidence indicate that TF signaling via G protein-coupled protease-activated
      receptors (PAR2, PAR1) additionally drives multiple aspects of the metabolic
      syndrome. TF-PAR2 signaling in adipocytes contributes to diet-induced obesity by
      decreasing metabolism and energy expenditure, whereas TF-PAR2 signaling in
      hematopoietic and myeloid cells drives adipose tissue inflammation, hepatic
      steatosis, and insulin resistance. TF-initiated coagulation leading to thrombin
      PAR1 signaling also contributes to diet-induced hepatic steatosis and
      inflammation in certain models. Thus, in obese patients, clinical markers of a
      prothrombotic state may indicate a risk for the development of complications of
      the metabolic syndrome. Furthermore, TF-induced signaling could provide new
      therapeutic targets for drug development at the intersection between obesity,
      inflammation, and thrombosis. 

PMID- 24092933
TI  - A phase 2 trial of azacitidine and gemtuzumab ozogamicin therapy in older
      patients with acute myeloid leukemia.
AB  - This trial tested the safety and efficacy of a regimen consisting of hydroxyurea
      followed by azacitidine, 75 mg/m(2) for 7 days, and gemtuzumab ozogamicin, 3
      mg/m(2) on day 8, in older patients with newly diagnosed acute myeloid leukemia.
      Those achieving a complete remission received 1 consolidation treatment followed
      by 4 cycles of azacitidine. The patients were stratified into good-risk (age 60
      69 years or performance status 0-1) and poor-risk (age >=70 years and performance
      status 2 or 3) groups. Specific efficacy and safety goals were defined as being
      supportive of further study of the regimen. Eighty-three patients were registered
      in the good-risk cohort and 59 in poor-risk cohort, with median age of 71 and 75
      years, respectively. In the good-risk group, 35 patients (44%) achieved a
      complete remission. Median relapse-free and overall survivals were 8 and 11
      months, respectively. Six patients (8%) died within 30 days of registration. In
      the poor-risk group, 19 (35%) achieved a complete remission. Median relapse-free
      and overall survivals were 7 and 11 months, respectively. Seven patients (14%)
      died early. The results of this trial met predefined goals for efficacy and
      safety for the poor-risk cohort but not the good-risk group. .

PMID- 24092934
TI  - The late endosomal adaptor molecule p14 (LAMTOR2) represents a novel regulator of
      Langerhans cell homeostasis.
AB  - Langerhans cells (LCs) are dendritic cells (DCs) residing in epithelia, where
      they critically regulate immunity and tolerance. The p14 adaptor molecule is part
      of the late endosomal/LAMTOR (lysosomal adaptor and mitogen-activated protein
      kinase and mammalian target of rapamycin [mTOR] activator/regulator) complex,
      thereby contributing to the signal transduction of the extracellular signaling
      regulated kinase (ERK) and the mTOR cascade. Furthermore, p14 represents an
      important regulator for endosomal sorting processes within the cell. Mutated,
      dysfunctional p14 leads to a human immunodeficiency disorder with
      endosomal/lysosomal defects in immune cells. Because p14 participates in the
      regulation of endosomal trafficking, growth factor signaling, and cell
      proliferation, we investigated the role of p14 in mouse DCs/LCs using a
      conditional knockout mouse model. p14-deficient animals displayed a virtually
      complete loss of LCs in the epidermis early after birth due to impaired
      proliferation and increased apoptosis of LCs. Repopulation analysis after
      application of contact sensitizer leads to the recruitment of a transient LC
      population, predominantly consisting of short-term LCs. The underlying molecular
      mechanism involves the p14-mediated disruption of the LAMTOR complex which
      results in the malfunction of both ERK and mTOR signal pathways. Hence, we
      conclude that p14 acts as a novel and essential regulator of LC homeostasis in
      vivo. 

PMID- 24092935
TI  - TRIM28 is essential for erythroblast differentiation in the mouse.
AB  - In previous mass spectrometry and coimmune precipitation studies, we identified
      tripartite motif-containing 28 (TRIM28; also known as transcriptional
      intermediary factor1beta and Kruppel-associated box-associated protein-1) as a
      cofactor that specifically copurified with an NR2C1/NR2C2 (TR2/TR4) orphan
      nuclear receptor heterodimer that previous studies had implicated as an
      embryonic/fetal beta-type globin gene repressor. TRIM28 has been characterized as
      a transcriptional corepressor that can associate with many different
      transcription factors and can play functional roles in multiple tissues and cell
      types. Here, we tested the contribution of TRIM28 to globin gene regulation and
      erythropoiesis using a conditional loss-of-function in vivo model. We discovered
      that Trim28 genetic loss in the adult mouse leads to defective immature
      erythropoiesis in the bone marrow and consequently to anemia. We further found
      that TRIM28 controls erythropoiesis in a cell-autonomous manner by inducibly
      deleting Trim28 exclusively in hematopoietic cells. Finally, in the absence of
      TRIM28, we observed increased apoptosis as well as diminished expression of
      multiple erythroid transcription factors and heme biosynthetic enzymes in
      immature erythroid cells. Thus, TRIM28 is essential for the cell-autonomous
      development of immature erythroblasts in the bone marrow. 

PMID- 24092936
TI  - Diels-Alder reaction for tumor pretargeting: in vivo chemistry can boost tumor
      radiation dose compared with directly labeled antibody.
AB  - Current pretargeting systems use noncovalent biologic interactions, which are
      prone to immunogenicity. We previously developed a novel approach based on the
      bioorthogonal reaction between a radiolabeled tetrazine and an antibody
      conjugated trans-cyclooctene (TCO). However, the tumor-to-blood ratio was low due
      to reaction with freely circulating antibody-TCO. METHODS: Here we developed 2
      tetrazine-functionalized clearing agents that enable rapid reaction with and
      removal of a TCO-tagged antibody (CC49) from blood. Next, we incorporated this
      approach into an optimized pretargeting protocol in LS174T-bearing mice. Then we
      compared the pretargeted (177)Lu-labeled tetrazine with (177)Lu-labeled CC49. The
      biodistribution data were used for mouse and human dosimetry calculations.
      RESULTS: The use of a clearing agent led to a doubling of the tetrazine tumor
      uptake and a 125-fold improvement of the tumor-to-blood ratio at 3 h after
      tetrazine injection. Mouse dosimetry suggested that this should allow for an 8
      fold higher tumor dose than is possible with nonpretargeted radioimmunotherapy.
      Also, humans treated with CC49-TCO-pretargeted (177)Lu-tetrazine would receive a
      dose to nontarget tissues 1 to 2 orders of magnitude lower than with directly
      labeled CC49. CONCLUSION: The in vivo performance of chemical pretargeting falls
      within the range of results obtained for the clinically validated pretargeting
      approaches in mice, with the advantage of potentially allowing for fractionated
      radiotherapy as a result of a lower likelihood of immunogenicity. These findings
      demonstrate that biologic pretargeting concepts can be translated to rapid
      bioorthogonal chemical approaches with retained potential.

PMID- 24092937
TI  - The SNMMI and EANM practice guideline for small-bowel and colon transit 1.0.

PMID- 24092938
TI  - Radiation dose of the P-glycoprotein tracer 11C-laniquidar.
AB  - Resistance to current drug therapy is an important issue in the treatment of
      epilepsy. Inadequate access of central nervous system drugs to their targets in
      the brain may be caused by overexpression or overactivity of multidrug
      transporters, such as P-glycoprotein (P-gp), at the blood-brain barrier.
      Laniquidar, an inhibitor of P-gp, has been labeled with (11)C for use in PET
      studies of P-gp expression in humans. Given potential interspecies differences in
      biodistribution, the purpose of this study was to ensure safe use of (11)C
      laniquidar by determining the dosimetry of (11)C-laniquidar using whole-body PET
      studies. METHODS: Six healthy volunteers were subjected to a series of 10 whole
      body PET scans within approximately 70 min. Five blood samples were taken during
      the series. RESULTS: High uptake of (11)C-laniquidar was seen in liver, spleen,
      kidneys, and lung, whereas brain uptake was low. The effective dose for (11)C
      laniquidar was 4.76 +/- 0.13 and 3.69 +/- 0.01 MUSv.MBq(-1) for women and men,
      respectively. CONCLUSION: Biodistribution and measured effective dose indicate
      that (11)C-laniquidar is a safe tracer for PET imaging, with a total dose of
      about 2 mSv for a brain PET/CT protocol.

PMID- 24092939
TI  - Longitudinal evaluation of left ventricular substrate metabolism, perfusion, and
      dysfunction in the spontaneously hypertensive rat model of hypertrophy using
      small-animal PET/CT imaging.
AB  - Myocardial metabolic and perfusion imaging is a vital tool for understanding the
      physiologic consequences of heart failure. We used PET imaging to examine the
      longitudinal kinetics of (18)F-FDG and 14(R,S)-(18)F-fluoro-6-thia-heptadecanoic
      acid ((18)F-FTHA) as analogs of glucose and fatty acid (FA) to quantify metabolic
      substrate shifts with the spontaneously hypertensive rat (SHR) as a model of left
      ventricular hypertrophy (LVH) and failure. Myocardial perfusion and left
      ventricular function were also investigated using a newly developed radiotracer
      (18)F-fluorodihydrorotenol ((18)F-FDHROL). METHODS: Longitudinal dynamic
      electrocardiogram-gated small-animal PET/CT studies were performed with 8 SHR and
      8 normotensive Wistar-Kyoto (WKY) rats over their life cycle. We determined the
      myocardial influx rate constant for (18)F-FDG and (18)F-FTHA (Ki(FDG) and
      Ki(FTHA), respectively) and the wash-in rate constant for (18)F-FDHROL
      (K1(FDHROL)). (18)F-FDHROL data were also used to quantify left ventricular
      ejection fraction (LVEF) and end-diastolic volume (EDV). Blood samples were drawn
      to independently measure plasma concentrations of glucose, insulin, and free
      fatty acids (FFAs). RESULTS: Ki(FDG) and Ki(FTHA) were higher in SHRs than WKY
      rats (P < 3 * 10(-8) and 0.005, respectively) independent of age. A decrease in
      Ki(FDG) with age was evident when models were combined (P = 0.034). The SHR
      exhibited higher K1(FDHROL) (P < 5 * 10(-6)) than the control, with no age
      dependent trends in either model (P = 0.058). Glucose plasma concentrations were
      lower in SHRs than controls (P < 6 * 10(-12)), with an age-dependent rise for WKY
      rats (P < 2 * 10(-5)). Insulin plasma concentrations were higher in SHRs than
      controls (P < 3 * 10(-3)), with an age-dependent decrease when models were
      combined (P = 0.046). FFA levels were similar between models (P = 0.374), but an
      increase with age was evident only in SHR (P < 7 * 10(-6)). CONCLUSION: The SHR
      exhibited alterations in myocardial substrate use at 8 mo characterized by
      increased glucose and FA utilizations. At 20 mo, the SHR had LVH characterized by
      decreased LVEF and increased EDV, while simultaneously sustaining higher glucose
      and similar FA utilizations (compared with WKY rats), which indicates
      maladaptation of energy substrates in the failing heart. Elevated K1(FDHROL) in
      the SHR may reflect elevated oxygen consumption and decreased capillary density
      in the hypertrophied heart. From our findings, metabolic changes appear to
      precede mechanical changes of LVH progression in the SHR model.

PMID- 24092940
TI  - 18F-FDG PET/CT for early prediction of response to neoadjuvant lapatinib,
      trastuzumab, and their combination in HER2-positive breast cancer: results from
      Neo-ALTTO.
AB  - Molecular imaging receives increased attention for selecting patients who will
      benefit from targeted anticancer therapies. Neo-ALTTO (Neoadjuvant Lapatinib
      and/or Trastuzumab Treatment Optimisation) enrolled 455 women with invasive human
      epidermal growth factor receptor 2 (HER2)-positive breast cancer and compared
      rates of pathologic complete response (pCR) to neoadjuvant lapatinib,
      trastuzumab, and their combination. Each anti-HER2 therapy was given alone for 6
      wk, followed by 12 wk of the same therapy plus weekly paclitaxel. The early
      metabolic effects of the anti-HER2 therapies on the primary tumors and their
      predictive values for pCR were assessed in a subset of patients. METHODS: Eighty
      six patients underwent (18)F-FDG PET/CT at baseline and weeks 2 and 6 of anti
      HER2 treatment. An imaging core laboratory provided central validation, and 2
      independent reviewers, masked to assigned treatment arm and clinical outcomes,
      performed consensus (18)F-FDG PET/CT readings. Maximum standardized uptake value
      (SUVmax) reductions from baseline were used to measure metabolic response.
      RESULTS: Seventy-seven of the 86 enrolled patients presented an evaluable
      baseline (18)F-FDG PET/CT scan; of these, 68 and 66 were evaluable at weeks 2 and
      6, respectively. Metabolic responses in the primary tumors were evident after 2
      wk of targeted therapy and correlated highly with metabolic responses at week 6
      (R(2) = 0.81). pCRs were associated with greater SUVmax reductions at both time
      points. Mean SUVmax reductions for pCR and non-pCR, respectively, were 54.3%
      versus 32.8% at week 2 (P = 0.02) and 61.5% versus 34.1% at week 6 (P = 0.02).
      (18)F-FDG PET/CT metabolic response rates at weeks 2 and 6 were 71.6% and 60%,
      respectively using European Organization for Research and Treatment of Cancer
      criteria; pCR rates were twice as high for (18)F-FDG PET/CT responders than
      nonresponders (week 2: 42% vs. 21%, P = 0.12; week 6: 44% vs. 19%, P = 0.05).
      CONCLUSION: Early metabolic assessment using (18)F-FDG PET/CT can identify
      patients with an increased likelihood of pCR after neoadjuvant trastuzumab,
      lapatinib, or their combination when given with chemotherapy.

PMID- 24092941
TI  - Burden of adhesions in abdominal and pelvic surgery: systematic review and met
      analysis.
AB  - OBJECTIVE: To estimate the disease burden of the most important complications of
      postoperative abdominal adhesions: small bowel obstruction, difficulties at
      reoperation, infertility, and chronic pain. DESIGN: Systematic review and meta
      analyses. DATA SOURCES: Searches of PubMed, Embase, and Central, from January
      1990 to December 2012, without restrictions to publication status or language.
      STUDY SELECTION: All types of studies reporting on the incidence of adhesion
      related complications were considered. DATA EXTRACTION AND ANALYSIS: The primary
      outcome was the incidence of adhesive small bowel obstruction in patients with a
      history of abdominal surgery. Secondary outcomes were the incidence of small
      bowel obstruction by any cause, difference in operative time, enterotomy during
      adhesiolysis, and pregnancy rate after abdominal surgery. Subgroup and
      sensitivity analyses were done to study the robustness of the results. A random
      effects model was used to account for heterogeneity between studies. RESULTS: We
      identified 196 eligible papers. Heterogeneity was considerable for almost all
      meta-analyses. The origin of heterogeneity could not be explained by study
      design, study quality, publication date, anatomical site of operation, or
      operative technique. The incidence of small bowel obstruction by any cause after
      abdominal surgery was 9% (95% confidence interval 7% to 10%; I(2)=99%). the
      incidence of adhesive small bowel obstruction was 2% (2% to 3%; I(2)=93%);
      presence of adhesions was generally confirmed by emergent reoperation. In
      patients with a known cause of small bowel obstruction, adhesions were the single
      most common cause (56%, 49% to 64%; I(2)=96%). Operative time was prolonged by 15
      minutes (95% confidence interval 9.3 to 21.1 minutes; I(2)=85%) in patients with
      previous surgery. Use of adhesiolysis resulted in a 6% (4% to 8%; I(2)=89%)
      incidence of iatrogenic bowel injury. The pregnancy rate after colorectal surgery
      in patients with inflammatory bowel disease was 50% (37% to 63%; I(2)=94%), which
      was significantly lower than the pregnancy rate in medically treated patients
      (82%, 70% to 94%; I(2)=97%). CONCLUSIONS: This review provides detailed and
      systematically analysed knowledge of the disease burden of adhesions.
      Complications of postoperative adhesion formation are frequent, have a large
      negative effect on patients' health, and increase workload in clinical practice.
      The quantitative effects should be interpreted with caution owing to large
      heterogeneity. REGISTRATION: The review protocol was registered through PROSPERO
      (CRD42012003180).

PMID- 24092943
TI  - Thousands of health workers furloughed as US government shuts down.

PMID- 24092944
TI  - Dr Foster is asked to review surgeons' performance after 14 year hospital feud.

PMID- 24092945
TI  - Doctors should accept they are no longer primary decision makers in care, says
      think tank.

PMID- 24092942
TI  - Blood pressure lowering and major cardiovascular events in people with and
      without chronic kidney disease: meta-analysis of randomised controlled trials.
AB  - OBJECTIVE: To define the cardiovascular effects of lowering blood pressure in
      people with chronic kidney disease. DESIGN: Collaborative prospective meta
      analysis of randomised trials. DATA SOURCES AND ELIGIBILITY: Participating
      randomised trials of drugs to lower blood pressure compared with placebo or each
      other or that compare different blood pressure targets, with at least 1000
      patient years of follow-up per arm. MAIN OUTCOME MEASURES: Major cardiovascular
      events (stroke, myocardial infarction, heart failure, or cardiovascular death) in
      composite and individually and all cause death. PARTICIPANTS: 26 trials (152,290
      participants), including 30,295 individuals with reduced estimated glomerular
      filtration rate (eGFR), which was defined as eGFR <60 mL/min/1.73 m(2). DATA
      EXTRACTION: Individual participant data were available for 23 trials, with
      summary data from another three. Meta-analysis according to baseline kidney
      function was performed. Pooled hazard ratios per 5 mm Hg lower blood pressure
      were estimated with a random effects model. RESULTS: Compared with placebo, blood
      pressure lowering regimens reduced the risk of major cardiovascular events by
      about a sixth per 5 mm Hg reduction in systolic blood pressure in individuals
      with (hazard ratio 0.83, 95% confidence interval 0.76 to 0.90) and without
      reduced eGFR (0.83, 0.79 to 0.88), with no evidence for any difference in effect
      (P=1.00 for homogeneity). The results were similar irrespective of whether blood
      pressure was reduced by regimens based on angiotensin converting enzyme
      inhibitors, calcium antagonists, or diuretics/beta blockers. There was no
      evidence that the effects of different drug classes on major cardiovascular
      events varied between patients with different eGFR (all P>0.60 for homogeneity).
      CONCLUSIONS: Blood pressure lowering is an effective strategy for preventing
      cardiovascular events among people with moderately reduced eGFR. There is little
      evidence from these overviews to support the preferential choice of particular
      drug classes for the prevention of cardiovascular events in chronic kidney
      disease.

PMID- 24092946
TI  - An experimental study of the structure of laminar premixed flames of
      ethanol/methane/oxygen/argon.
AB  - The structures of three laminar premixed stoichiometric flames at low pressure
      (6.7 kPa): a pure methane flame, a pure ethanol flame and a methane flame doped
      by 30% of ethanol, have been investigated and compared. The results consist of
      concentration profiles of methane, ethanol, O2, Ar, CO, CO2, H2O, H2, C2H6, C2H4,
      C2H2, C3H8, C3H6, p-C3H4, a-C3H4, CH2O, CH3HCO, measured as a function of the
      height above the burner by probe sampling followed by on-line gas chromatography
      analyses. Flame temperature profiles have been also obtained using a PtRh (6%)
      PtRh (30%) type B thermocouple. The similarities and differences between the
      three flames were analyzed. The results show that, in these three flames, the
      concentration of the C2 intermediates is much larger than that of the C3 species.
      In general, mole fraction of all intermediate species in the pure ethanol flame
      is the largest, followed by the doped flame, and finally the pure methane flame.

PMID- 24092947
TI  - Mass spectra of cyclic ethers formed in the low-temperature oxidation of a series
      of n-alkanes.
AB  - Cyclic ethers are important intermediate species formed during the low
      temperature oxidation of hydrocarbons. Along with ketones and aldehydes, they
      could consequently represent a significant part of the heavy oxygenated
      pollutants observed in the exhaust gas of engines. Apart a few of them such as
      ethylene oxide and tetrahydrofuran, cyclic ethers have not been much studied and
      very few of them are available for calibration and identification. Electron
      impact mass spectra are available for very few of them, making their detection in
      the exhaust emissions of combustion processes very difficult. The main goal of
      this study was to complete the existing set of mass spectra for this class of
      molecules. Thus cyclic ethers have been analyzed in the exhaust gases of a jet
      stirred reactor in which the low-temperature oxidation of a series of n-alkanes
      was taking place. Analyzes were performed by gas chromatography coupled to mass
      spectrometry and to MS/MS. The second goal of this study was to derive some rules
      for the fragmentation of cyclic ethers in electron impact mass spectrometry and
      allow the identification of these species when no mass spectrum is available.

PMID- 24092948
TI  - Chemical Kinetics Laboratory Discussion Worksheet.
AB  - A laboratory discussion worksheet and its answer key provide instructors and
      students a discussion model to further the students' understanding of chemical
      kinetics. This discussion worksheet includes a section for students to augment
      their previous knowledge about chemical kinetics measurements, an initial check
      on students' understanding of basic concepts, a group participation model where
      students work on solving complex-conceptual problems, and a conclusion to help
      students connect this discussion to their laboratory or lecture class.
      Additionally, the worksheet has a detailed solution to a more advanced problem to
      help students understand how the concepts they have put together relate to
      problems they will encounter during later formal assessments.

PMID- 24092949
TI  - Mexican-origin Mothers' and Fathers' Involvement in Adolescents' Peer
      Relationships: A Pattern-Analytic Approach.
AB  - Using latent profile analysis, this study examined patterns of mother-father
      involvement in adolescents' peer relationships along three dimensions, support,
      guidance, and restrictions, in 240 Mexican-origin families. Three profiles were
      identified: (a) High Mother Involvement (mothers higher than fathers on all three
      dimensions); (b) High Support/Congruent (mothers and fathers reported the highest
      levels of peer support and similar levels of guidance and restrictions); and (c)
      Differentiated (more guidance and restrictions by fathers than by mothers,
      similar levels of parent support). These profiles were linked to mothers' and
      fathers' familism values, traditional patriarchal gender role attitudes, and
      socioeconomic status, and to adolescents' friendship intimacy and risky behaviors
      measured longitudinally from early to late adolescence. Adolescent gender
      moderated the linkages between parents' involvement in adolescents' peer
      relationships and youth adjustment.

PMID- 24092950
TI  - Sex differences in neural efficiency: Are they due to the stereotype threat
      effect?
AB  - The neural efficiency hypothesis postulates a more efficient use of brain
      resources in more intelligent people as compared to less intelligent ones.
      However, this relationship was found to be moderated by sex and task content.
      While the phenomenon of neural efficiency was previously supported for men when
      performing visuo-spatial tasks it occurred for women only when performing verbal
      tasks. One possible explanation for this finding could be provided by the well
      studied phenomenon called stereotype threat. Stereotype threat arises when a
      negative stereotype of one's own group is made salient and can result in behavior
      that confirms the stereotype. Overall, 32 boys and 31 girls of varying
      intellectual ability were tested with a mental rotation task, either under a
      stereotype exposure or a no-stereotype exposure condition while measuring their
      EEG. The behavioral results show that an activated negative stereotype not
      necessarily hampers the performance of girls. Physiologically, a confirmation of
      the neural efficiency phenomenon was only obtained for boys working under a no
      stereotype exposure condition. This result pattern replicates previous findings
      without threat and thus suggests that sex differences in neural efficiency during
      visuo-spatial tasks may not be due to the stereotype threat effect.

PMID- 24092951
TI  - Combining micromagnetism and magnetostatic Maxwell equations for multiscale
      magnetic simulations.
AB  - Magnetostatic Maxwell equations and the Landau-Lifshitz-Gilbert (LLG) equation
      are combined to a multiscale method, which allows to extend the problem size of
      traditional micromagnetic simulations. By means of magnetostatic Maxwell
      equations macroscopic regions can be handled in an averaged and stationary sense,
      whereas the LLG allows to accurately describe domain formation as well as
      magnetization dynamics in some microscopic subregions. The two regions are
      coupled by means of their strayfield and the combined system is solved by an
      optimized time integration scheme.

PMID- 24092953
TI  - Extreme point and halving edge search in abstract order types.
AB  - Many properties of finite point sets only depend on the relative position of the
      points, e.g., on the order type of the set. However, many fundamental algorithms
      in computational geometry rely on coordinate representations. This includes the
      straightforward algorithms for finding a halving line for a given planar point
      set, as well as finding a point on the convex hull, both in linear time. In his
      monograph Axioms and Hulls, Knuth asks whether these problems can be solved in
      linear time in a more abstract setting, given only the orientation of each point
      triple, i.e., the set's chirotope, as a source of information. We answer this
      question in the affirmative. More precisely, we can find a halving line through
      any given point, as well as the vertices of the convex hull edges that are
      intersected by the supporting line of any two given points of the set in linear
      time. We first give a proof for sets realizable in the Euclidean plane and then
      extend the result to non-realizable abstract order types.

PMID- 24092952
TI  - Effects of verb meaning on lexical integration in agrammatic aphasia: Evidence
      from eyetracking.
AB  - Relatively little is known about the time course of access to the lexical
      representations of verbs in agrammatic aphasia and its effects on the prediction
      and integration of the verb's arguments. The present study used visual-world
      eyetracking to test whether verb meaning can be used by agrammatic aphasic
      individuals to predict and facilitate the integration of a subsequent noun
      argument. Nine adults with agrammatic aphasia and ten age-matched controls
      participated in the study. In Experiment 1, participants viewed arrays of four
      objects (e.g., jar, plate, stick, pencil) while listening to sentences containing
      either a restrictive verb that was semantically compatible only with the target
      object or an unrestrictive verb compatible with all four objects (e.g., Susan
      will open/break the jar). For both participant groups, the restrictive condition
      elicited more fixations to the target object immediately after the verb.
      Experiment 2 differed from Experiment 1 in that the auditory sentences presented
      were incomplete (e.g., Susan will open/break the...). For controls, restrictive
      verbs elicited more target fixations immediately after the verb; however, the
      effects of verb type were noted downstream from the verb for the aphasic
      listeners. The results suggest that individuals with agrammatic aphasia have
      preserved ability to use verb information to facilitate integration of overt
      arguments, but prediction of upcoming arguments is impaired. Impaired lexical
      semantic prediction processes may be caused by damage to the left inferior
      frontal gyrus, which has been argued to support higher-level lexical processes.

PMID- 24092954
TI  - Automatic and Quantitative Measurement of Collagen Gel Contraction Using Model
      Guided Segmentation.
AB  - Quantitative measurement of collagen gel contraction plays a critical role in the
      field of tissue engineering because it provides spatial-temporal assessment
      (e.g., changes of gel area and diameter during the contraction process)
      reflecting the cell behaviors and tissue material properties. So far the
      assessment of collagen gels relies on manual segmentation, which is time
      consuming and suffers from serious intra- and inter-observer variability. In this
      study, we propose an automatic method combining various image processing
      techniques to resolve these problems. The proposed method first detects the
      maximal feasible contraction range of circular references (e.g., culture dish)
      and avoids the interference of irrelevant objects in the given image. Then, a
      three-step color conversion strategy is applied to normalize and enhance the
      contrast between the gel and background. We subsequently introduce a deformable
      circular model (DCM) which utilizes regional intensity contrast and circular
      shape constraint to locate the gel boundary. An adaptive weighting scheme was
      employed to coordinate the model behavior, so that the proposed system can
      overcome variations of gel boundary appearances at different contraction stages.
      Two measurements of collagen gels (i.e., area and diameter) can readily be
      obtained based on the segmentation results. Experimental results, including 120
      gel images for accuracy validation, showed high agreement between the proposed
      method and manual segmentation with an average dice similarity coefficient larger
      than 0.95. The results also demonstrated obvious improvement in gel contours
      obtained by the proposed method over two popular, generic segmentation methods.

PMID- 24092955
TI  - Modelling human embryoid body cell adhesion to a combinatorial library of polymer
      surfaces.
AB  - Designing materials to control biology is an intense focus of biomaterials and
      regenerative medicine research. Discovering and designing materials with
      appropriate biological compatibility or active control of cells and tissues is
      being increasingly undertaken using high throughput synthesis and assessment
      methods. We report a relatively simple but powerful machine-learning method of
      generating models that link microscopic or molecular properties of polymers or
      other materials to their biological effects. We illustrate the potential of these
      methods by developing the first robust, predictive, quantitative, and purely
      computational models of adhesion of human embryonic stem cell embryoid bodies
      (hEB) to the surfaces of a 496-member polymer micro array library.

PMID- 24092956
TI  - Monitoring the effects of different conservation treatments on paper-infecting
      fungi.
AB  - Fungi are among the most degradative organisms inducing biodeterioration of paper
      based items of cultural heritage. Appropriate conservation measures and
      restoration treatments to deal with fungal infections include mechanical,
      chemical, and biological methods, which entail effects on the paper itself and
      health hazards for humans. Three different conservation treatments, namely freeze
      drying, gamma rays, and ethylene oxide fumigation, were compared and monitored to
      assess their short- (one month, T1) and long-term (one year, T2) effectiveness to
      inhibit fungal growth. After the inoculation with fungi possessing cellulose
      hydrolysis ability - Chaetomium globosum, Trichoderma viride, and Cladosporium
      cladosporioides - as single strains or as a mixture, different quality paper
      samples were treated and screened for fungal viability by culture-dependent and 
      independent techniques. Results derived from both strategies were contradictory.
      Both gamma irradiation and EtO fumigation showed full efficacy as disinfecting
      agents when evaluated with cultivation techniques. However, when using molecular
      analyses, the application of gamma rays showed a short-term reduction in DNA
      recovery and DNA fragmentation; the latter phenomenon was also observed in a
      minor degree in samples treated with freeze-drying. When RNA was used as an
      indicator of long-term fungal viability, differences in the RNA recovery from
      samples treated with freeze-drying or gamma rays could be observed in samples
      inoculated with the mixed culture. Only the treatment with ethylene oxide proved
      negative for both DNA and RNA recovery. Therefore, DNA fragmentation after an
      ethylene oxide treatment can hamper future paleogenetic and archaeological
      molecular studies on the objects.

PMID- 24092957
TI  - Microscopic, chemical, and molecular-biological investigation of the decayed
      medieval stained window glasses of two Catalonian churches.
AB  - We investigated the decayed historical church window glasses of two Catalonian
      churches, both under Mediterranean climate. Glass surfaces were studied by
      scanning electron microscopy (SEM), energy dispersive spectrometry (EDS), and X
      ray diffraction (XRD). Their chemical composition was determined by wavelength
      dispersive spectrometry (WDS) microprobe analysis. The biodiversity was
      investigated by molecular methods: DNA extraction from glass, amplification by
      PCR targeting the16S rRNA and ITS regions, and fingerprint analyses by denaturing
      gradient gel electrophoresis (DGGE). Clone libraries containing either PCR
      fragments of the bacterial 16S rDNA or the fungal ITS regions were screened by
      DGGE. Clone inserts were sequenced and compared with the EMBL database.
      Similarity values ranged from 89 to 100% to known bacteria and fungi. Biological
      activity in both sites was evidenced in the form of orange patinas, bio-pitting,
      and mineral precipitation. Analyses revealed complex bacterial communities
      consisting of members of the phyla Proteobacteria, Bacteroidetes, Firmicutes, and
      Actinobacteria. Fungi showed less diversity than bacteria, and species of the
      genera Cladosporium and Phoma were dominant. The detected Actinobacteria and
      fungi may be responsible for the observed bio-pitting phenomenon. Moreover, some
      of the detected bacteria are known for their mineral precipitation capabilities.
      Sequence results also showed similarities with bacteria commonly found on
      deteriorated stone monuments, supporting the idea that medieval stained glass
      biodeterioration in the Mediterranean area shows a pattern comparable to that on
      stone.

PMID- 24092958
TI  - Monitoring of technical variation in quantitative high-throughput datasets.
AB  - High-dimensional datasets can be confounded by variation from technical sources,
      such as batches. Undetected batch effects can have severe consequences for the
      validity of a study's conclusion(s). We evaluate high-throughput RNAseq and
      miRNAseq as well as DNA methylation and gene expression microarray datasets,
      mainly from the Cancer Genome Atlas (TCGA) project, in respect to technical and
      biological annotations. We observe technical bias in these datasets and discuss
      corrective interventions. We then suggest a general procedure to control study
      design, detect technical bias using linear regression of principal components,
      correct for batch effects, and re-evaluate principal components. This procedure
      is implemented in the R package swamp, and as graphical user interface software.
      In conclusion, high-throughput platforms that generate continuous measurements
      are sensitive to various forms of technical bias. For such data, monitoring of
      technical variation is an important analysis step. 

PMID- 24092959
TI  - Shared decision making: a fundamental tenet in a conceptual framework of
      integrative healthcare delivery.
AB  - With the increased usage of complementary and alternative medicine (CAM) in the
      US comes a need for evidence-based and integrated care systems which encourage
      open communication between patients and providers. This paper introduces a
      conceptual framework for integrative care delivery, with shared decision making
      being the "connecting force" between holistic treatment and improved health
      outcomes for patients. 

PMID- 24092960
TI  - Comparison of SWAP and SAP on the point of glaucoma conversion.
AB  - BACKGROUND: The purpose of this study was to compare the two perimetric
      modalities, SWAP (short wavelength automated perimetry) and SAP (standard
      automated perimetry), on the point of conversion to glaucoma. METHODS: In this
      prospective, longitudinal, follow-up study, 282 patients with ocular hypertension
      were recruited consecutively and tested with both SAP and SWAP annually for 5
      years or until the onset of conversion to glaucoma. SAP and SWAP perimetry was
      performed with the Humphrey Field Analyzer II using the 24-2 full-threshold test.
      Abnormality for both SAP and SWAP fields was determined on the pattern deviation
      plot and defined as either a) one point below the 0.5% probability level or b) a
      cluster of 2 or more points below 1% or c) a cluster of 3 or more points below 2%
      or d) a cluster of 4 or more points below 5%. Abnormal tests had to be confirmed
      on a subsequent test within one year to be classified as conversion. RESULTS: Of
      the 282 patients initially recruited, 32 were excluded. Of the 250 remaining
      patients, a total of 38 converted during the follow-up period; 36.8% of
      conversions were detected earlier with SWAP, 29% simultaneously, and 34.2% were
      not detected with SWAP during the follow-up period; 2.4% of patients showed SWAP
      visual field loss that did not result in conversion during the follow-up period.
      CONCLUSION: The results in our study are inconclusive. There were patients with
      earlier, simultaneous, or no SWAP conversion, with SAP conversion as the golden
      standard criterion. One should consider both SAP and SWAP with confirmation when
      visual field loss is evident to maximize early detection of glaucoma, because it
      appears that each method identifies early glaucoma in a subset of patients and
      these subsets overlap only partially.

PMID- 24092961
TI  - Prospective evaluation of visual outcomes with three presbyopia-correcting
      intraocular lenses following cataract surgery.
AB  - PURPOSE: To compare the visual acuity and quality of vision achieved with three
      widely-used intraocular lenses (IOLs) in subjects with bilateral cataracts.
      PATIENTS AND METHODS: This three-arm, parallel, prospective, partially masked,
      single-surgeon study randomized 78 subjects to receive bilateral Crystalens(r)
      Advanced Optics (AO) accommodating IOLs, AcrySof(r) IQ ReSTOR(r) +3.0 multifocal
      IOLs, or TECNIS(r) Multifocal IOLs. Examinations were assessed through days 120
      to 180. RESULTS: The Crystalens AO group had statistically significantly better
      monocular and binocular, high-contrast (HC) and low-contrast (LC) uncorrected
      intermediate visual acuity, HC and LC distance-corrected intermediate visual
      acuity, and significantly fewer monocular and binocular halos and starbursts than
      did the ReSTOR and TECNIS groups. Monocular and binocular, HC and LC uncorrected
      near visual acuity exhibited no significant differences among the three lenses.
      For monocular and binocular HC distance-corrected near visual acuity, the
      Crystalens AO performed significantly better than the TECNIS and was not
      significantly different from the ReSTOR. For monocular and binocular LC distance
      corrected near visual acuity, the Crystalens AO performed significantly better
      than both the ReSTOR and the TECNIS. Contrast sensitivity was clinically similar
      between groups. The Crystalens AO produced statistically fewer halos and
      starbursts. CONCLUSION: All three IOLs had excellent uncorrected acuity results
      at all distances and had good safety, confirming the established safety and
      effectiveness of these IOLs. Distance and near vision were similar between all
      three IOLs, and the Crystalens AO provided statistically significantly better
      intermediate vision.

PMID- 24092962
TI  - De novo ocular hypertension after Descemet stripping endothelial keratoplasty:
      comparative 3-year incidence, risk factors, and outcomes.
AB  - OBJECTIVE: To compare the 3-year incidence of de novo ocular hypertension (OHT)
      after Descemet stripping automated endothelial keratoplasty (DSAEK) and
      penetrating keratoplasty (PK). For DSAEK, to evaluate predictors for OHT and 2
      year outcomes after OHT development. METHODS: This was a review of the
      prospective Singapore Corneal Transplant Study at a single tertiary referral
      center. Consecutive DSAEKs and PKs for Fuchs' endothelial dystrophy (FED) and
      pseudophakic bullous keratopathy (PBK) in eyes without pre-existing glaucoma were
      analyzed. OHT incidence after DSAEK and PK were compared using Kaplan-Meier
      survival analysis, and OHT risk factors identified using Cox proportional
      regression. OHT was defined: intraocular pressure (IOP) >= 24 mmHg or >= 10 mmHg
      from baseline. Secondary outcomes 2 years after OHT development in DSAEK were
      rates of glaucoma medical therapy failure, IOP success, graft failure and
      rejection, and best-spectacle corrected visual acuity (BSCVA). RESULTS: There
      were 108 (96.4%) DSAEKs and 216 (96%) PKs. The 1-, 2- and 3-year de novo OHT
      incidence was not significantly different between DSAEK (36.1%, 47.2%, 47.2%,
      respectively) and PK (35.7%, 44.9%, 45.8%, respectively; P = 0.914). OHT
      incidence did not differ in subgroup analyses of multiple clinical variables (P >
      0.1). OHT predictors after DSAEK were: fellow eye glaucoma (hazard ratio [HR]
      3.20, P = 0.004), age <60 years (HR 2.41, P = 0.016), concurrent
      goniosynechiolysis (HR 3.29, P = 0.021), post-graft complications or procedures
      (HR 2.85, P = 0.006). Two years after OHT onset, 29.7% of DSAEKs failed glaucoma
      medical therapy requiring trabeculectomy. Complete and qualified IOP success was
      achieved in 23.5% and 76.5%, respectively. Graft failure developed in 9.8% and
      graft rejection in 5.9%. At 6 months, 1, and 2 years from OHT onset, 86.3%,
      88.3%, and 92.1% achieved BSCVA 20/40, respectively. CONCLUSION: DSAEK and PK
      have comparable OHT risks. A significant 30% of DSAEK eyes with OHT require
      filtration surgery. Effective IOP control and good graft and visual outcomes are
      achieved with treatment.

PMID- 24092963
TI  - Surgical therapy versus observation for lamellar macular hole: a retrospective
      comparison study.
AB  - BACKGROUND: The purpose of this study was to compare anatomic and visual changes
      in patients with lamellar macular hole undergoing pars plana vitrectomy with
      those in patients undergoing follow-up only. METHODS: In this retrospective
      consecutive case series study, we evaluated two groups of eyes, comprising 19
      eyes from 19 patients with lamellar macular hole who underwent pars plana
      vitrectomy with internal limiting membrane peeling and 21 eyes from 21 patients
      with lamellar macular hole who had follow-up only. Corrected distance visual
      acuity (CDVA, in logMAR) and optical coherence tomography findings, including
      measurements of maximum diameter of lamellar defect and foveal thickness, and
      whether the inner segment/outer segment band was intact or not were documented at
      initial and follow-up examinations. RESULTS: At initial examination, mean CDVA
      was 0.54 logMAR in the study group and 0.51 logMAR in the control group, and 0.33
      logMAR and 0.55 logMAR, respectively, on final examination. In the study group,
      postoperative optical coherence tomography images were found to be normalized in
      ten patients (52.6%), improved in six (31.5%), unchanged in two (10.5%), and to
      have progressed to full-thickness macular hole in one (5.2%) in the intervention
      group, while all patients in the control group were found to have deteriorated
      within the follow-up period between March 2004 and June 2010. CONCLUSION: In
      patients with lamellar macular hole, combination treatment with pars plana
      vitrectomy and internal limiting membrane peeling appears to be effective, but
      further studies are required to establish new treatment modalities for patients
      who do not have a satisfactory outcome from treatment.

PMID- 24092964
TI  - Real-world variability in ranibizumab treatment and associated clinical, quality
      of life, and safety outcomes over 24 months in patients with neovascular age
      related macular degeneration: the HELIOS study.
AB  - INTRODUCTION: The aim of this study was to examine ranibizumab treatment patterns
      in "real-world" practice and clinical settings, as well as to assess quality of
      life outcomes over a 24-month period. MATERIALS AND METHODS: This was a
      prospective, observational, multicenter, open-label study of 0.5 mg of
      ranibizumab administered intravitreally. Patients were followed over 24 +/- 3
      months with intermediate data points at 6 +/- 2 months and 12 +/- 2 months, and a
      limited data point at 2.5 +/- 1 month that coincided with the end of the loading
      phase. Outcomes included visual acuity (Early Treatment Diabetic Retinopathy
      Study), visual function (National Eye Institute Visual Function Questionnaire-25
      [NEI VFQ-25]), quality of life (Health Utilities Index Mark III [HUI3]), and
      safety. RESULTS: A total of 267 patients with wet age-related macular
      degeneration (mean +/- standard deviation [SD] age = 78.5 +/- 7.3 years; 62.4%
      were female; 34.5% with dual eye involvement; 74.9% were treatment-naive) were
      treated (309 eyes were treated). The mean +/- SD Early Treatment Diabetic
      Retinopathy Study score at baseline was 56.3 +/- 14.3 letters. The mean +/- SD
      number of injections over 24 months was 7.6 +/- 4.1, including 2.5 +/- 0.7 and
      5.9 +/- 3.6 during the loading and maintenance phases, respectively, with
      corresponding treatment intervals of 4.8 +/- 1.4 weeks and 11.5 +/- 9.5 weeks,
      respectively. Improvements in visual acuity over baseline were reached at 2.5
      months and maintained at 6 months (both P < 0.0001). The mean visual acuity
      increase over baseline at 12 months was not significant (P = 0.08); the decline
      over baseline at 24 months statistically significant (P = 0.02). Overall, 94.3%
      of patients showed stable or improved disease at 6 months and 81.5% of patients
      showed stable or improved disease at 24 months. At 6 months, improvements over
      baseline were significant for VFQ-25 (P = 0.03) and HUI3 (P = 0.02), but not at
      12 months and 24 months. Improvements in VFQ-25 and HUI3 were maintained at 24
      months in 38% and 34% of patients, respectively. In total 78 serious adverse
      events were reported in 40 patients and 77 nonserious adverse events in 34
      patients. Nine serious adverse events and nine nonserious adverse events in 14
      patients were suspected to be related to ranibizumab treatment. CONCLUSION: The
      "real-world" clinical effectiveness of ranibizumab was evidenced by the initial
      improvements over baseline in visual acuity and quality of life, as well as the
      maintenance of these outcomes at baseline levels at 24 months, and this was
      observed under variable treatment conditions. The findings underscore the need
      for individualized treatment with regular monitoring to achieve optimal vision
      and quality of life outcomes.

PMID- 24092965
TI  - Profile of verteporfin and its potential for the treatment of central serous
      chorioretinopathy.
AB  - Central serous chorioretinopathy (CSCR) is an idiopathic disorder characterized
      by serous retinal detachments associated with focal leakage on fluorescein
      angiography and pigment epithelial detachments. While the majority of cases
      improve spontaneously over several months, a significant subset of patients
      advance to a chronic recurrent form of the disease with diffuse pigment
      epitheliopathy, foveal atrophy, scarring, and permanent visual loss. Photodynamic
      therapy (PDT) with verteporfn has been extensively studied as a potential
      therapeutic option for chronic cases. Multiple prospective interventional studies
      have demonstrated the efficacy of PDT for CSCR with significant functional and
      anatomic improvements achieved. Refinement of the PDT protocol has subsequently
      been performed in an effort to minimize adverse effects. Anti-vascular
      endothelial growth factor (anti-VEGF) agents, such as bevacizumab, have been
      utilized in the treatment of CSCR. Recent advances in imaging and functional
      testing have shed further light on possible pathophysiologic mechanisms of
      disease and post treatment changes induced by PDT. While the body of evidence
      supports PDT as an efficacious and relatively safe treatment for CSCR, further
      evaluation of the long-term efficacy and safety of PDT, as well as protocol
      improvements are required. 

PMID- 24092966
TI  - Combination therapy with triamcinolone acetonide and bevacizumab for the
      treatment of severe radiation maculopathy in patients with posterior uveal
      melanoma.
AB  - PURPOSE: To evaluate the role of intravitreal triamcinolone acetonide in patients
      who developed severe, visually compromising radiation maculopathy or progressed
      despite anti-angiogenic treatments. METHODS: An Institutional Review Board
      approved, consecutive, retrospective study from 2006 to 2009 of patients who
      developed severe, visually compromising radiation retinopathy manifesting as
      macular edema secondary to iodine-125 plaque brachytherapy for posterior uveal
      melanoma, were treated with a combination of intravitreal bevacizumab and
      intravitreal triamcinolone. Patients were evaluated with spectral domain optical
      coherence tomography (SD-OCT) at 2-4 month intervals following plaque removal.
      Treatment with intravitreal bevacizumab commenced at the first signs of visually
      compromising macular edema diagnosed with SD-OCT. Triamcinolone acetonide was
      administered to patients with severe maculopathy as consolidative therapy, or for
      patients that were refractory to repeated bevacizumab injections with persistent
      or worsening cystoid macular edema and lack of improvement or progressive
      worsening of best corrected visual acuity (BCVA). RESULTS: Twenty-five patients
      were evaluated after receiving a combination of intravitreal bevacizumab and
      triamcinolone. Initial treatment commenced at a mean of 14.5 (range of 2-42)
      months after plaque brachytherapy. Patients were given a mean of two injections
      (range 1-6) of triamcinolone acetonide, and a mean of 8.8 bevacizumab injections
      (range of 1-26) with a mean follow-up of 31.2 months. Radiation maculopathy upon
      first detection had a mean SD-OCT grade of 3.6 (median = 4), with an associated
      mean entry level BCVA of 20/70. Visual acuity at time of first intravitreal
      triamcinolone was 20/138. At last follow-up (mean of 45.5 months after plaque
      brachytherapy) mean BCVA was 20/136; however, 9 of 25 (36%) patients who
      presented with severe radiation maculopathy demonstrated 20/50 or better vision
      at last follow-up. CONCLUSION: This case series suggests a beneficial role for
      intravitreal triamcinolone as a consolidation treatment for patients who present
      with severe radiation maculopathy or as an adjuvant to bevacizumab for refractory
      or progressive maculopathy.

PMID- 24092967
TI  - Correlation between peripapillary retinal nerve fiber layer thickness and fundus
      autofluorescence in primary open-angle glaucoma.
AB  - PURPOSE: To investigate the relationship between retinal nerve fiber layer (RNFL)
      thickness and retinal pigment epithelium alterations in patients with advanced
      glaucomatous visual field defects. METHODS: A consecutive, prospective series of
      82 study eyes with primary open-angle glaucoma and advanced glaucomatous visual
      field defects were included in this study. All study participants underwent a
      full ophthalmic examination followed by visual field testing with standard
      automated perimetry as well as spectral-domain optical coherence tomography (SD
      OCT) for peripapillary RNFL thickness and Optos wide-field fundus
      autofluorescence (FAF) images. A pattern grid with corresponding locations
      between functional visual field sectors and structural peripapillary RNFL
      thickness was aligned to the FAF images at corresponding location. Mean FAF
      intensity (range: 0 = black and 255 = white) of each evaluated sector
      (superotemporal, temporal, inferotemporal, inferonasal, nasal, superonasal) was
      correlated with the corresponding peripapillary RNFL thickness obtained with SD
      OCT. RESULTS: Correlation analyses between sectoral RNFL thickness and
      standardized FAF intensity in the corresponding topographic retina segments
      revealed partly significant correlations with correlation coefficients ranging
      between 0.004 and 0.376 and were statistically significant in the temporal
      inferior central field (r = 0.324, P = 0.036) and the nasal field (r = 0.376, P =
      0.014). CONCLUSION: Retinal pigment epithelium abnormalities correlate with
      corresponding peripapillary RNFL damage, especially in the temporal inferior
      sector of patients with advanced glaucomatous visual field defects. A further
      evaluation of FAF as a potential predictive parameter for glaucomatous damage is
      necessary.

PMID- 24092968
TI  - In situ carcinoma of the conjunctiva: surgical excision associated with
      cryotherapy.
AB  - BACKGROUND: Although frequently underdiagnosed, squamous cell carcinoma is the
      most commonly observed malignancy of the conjunctiva. Multiple different
      treatments have been proposed to date. The purpose of this paper is to report our
      experience in the treatment of In situ carcinoma of the conjunctiva by surgical
      excision associated with cryotherapy. METHODS: Four eyes in four consecutive
      patients (two men and two women) of average age 53.2 (range 39-71) years at the
      time of diagnosis of ocular surface squamous neoplasia were treated by simple
      surgical excision and cryotherapy of the resulting surgical bed margins. In all
      cases, the diagnosis of in situ carcinoma was confirmed histopathologically.
      RESULTS: On histopathology, the edges of the surgical specimens were free of
      malignant cells in three of four patients. All patients showed excellent
      evolution without recurrence. Mean follow-up was 6.5 (range 2-14) years.
      CONCLUSION: In situ carcinoma of the conjunctiva may be simply and successfully
      treated with surgical excision and cryotherapy.

PMID- 24092969
TI  - Cataract surgery following KAMRA presbyopic implant.
AB  - Intrastromal corneal inlays are an emerging treatment for presbyopic patients.
      The KAMRATM small aperture inlay was the first such inlay to receive Conformite
      Europeenne (CE) marking in 2005. It has been shown to improve uncorrected near
      and intermediate visual acuity without adversely affecting uncorrected distance
      visual acuity. Due to the age of presbyopic patients, they may eventually develop
      cataracts. In two such cases, we found that cataract surgery with the KAMRA
      implant left in place was not technically more difficult, and that the surgical
      procedure could be improved by additional ocular rotations to improve
      visualization. Biometry readings were reliable, and it appeared that the SRK/T
      formula was accurate for calculation of intraocular lens power. Cataract surgery
      with the KAMRA implant left in situ is a viable option for patients. 

PMID- 24092970
TI  - Molecular Insights on Post-chemotherapy Retinoblastoma by Microarray Gene
      Expression Analysis.
AB  - PURPOSE: Management of Retinoblastoma (RB), a pediatric ocular cancer is limited
      by drug-resistance and drug-dosage related side effects during chemotherapy.
      Molecular de-regulation in post-chemotherapy RB tumors was investigated.
      MATERIALS AND METHODS: cDNA microarray analysis of two post-chemotherapy and one
      pre-chemotherapy RB tumor tissues was performed, followed by Principle Component
      Analysis, Gene ontology, Pathway Enrichment analysis and Biological Analysis
      Network (BAN) modeling. The drug modulation role of two significantly up
      regulated genes (p<=0.05) - Ect2 (Epithelial-cell-transforming-sequence-2), and
      PRAME (preferentially-expressed-Antigen-in-Melanoma) was assessed by qRT-PCR,
      immunohistochemistry and cell viability assays. RESULTS: Differential up
      regulation of 1672 genes and down-regulation of 2538 genes was observed in RB
      tissues (relative to normal adult retina), while 1419 genes were commonly de
      regulated between pre-chemotherapy and post- chemotherapy RB. Twenty one key gene
      ontology categories, pathways, biomarkers and phenotype groups harboring 250
      differentially expressed genes were dys-regulated (EZH2, NCoR1, MYBL2, RB1,
      STAMN1, SYK, JAK1/2, STAT1/2, PLK2/4, BIRC5, LAMN1, Ect2, PRAME and ABCC4).
      Differential molecular expressions of PRAME and Ect2 in RB tumors with and
      without chemotherapy were analyzed. There was neither up- regulation of MRP1, nor
      any significant shift in chemotherapeutic IC50, in PRAME over-expressed versus
      non-transfected RB cells. CONCLUSION: Cell cycle regulatory genes were dys
      regulated post-chemotherapy. Ect2 gene was expressed in response to chemotherapy
      induced stress. PRAME does not contribute to drug resistance in RB, yet its
      nuclear localization and BAN information, points to its possible regulatory role
      in RB.

PMID- 24092971
TI  - Design of indomethacin-loaded nanoparticles: effect of polymer matrix and
      surfactant.
AB  - Despite recent advances in nonsteroidal anti-inflammatory drug (NSAID)
      formulations, the design of targeted delivery systems to improve the efficacy and
      reduce side effects of NSAIDs continues to be a focus of much research. Enteric
      nanoparticles have been recognized as a potential system to reduce
      gastrointestinal irritations caused by NSAIDs. The aim of this study was to
      evaluate the effect of EUDRAGIT(r) L100, polyethylene glycol, and polysorbate 80
      on encapsulation efficiency of indomethacin within enteric nanoparticles.
      Formulations were developed based on a multilevel factorial design (three
      factors, two levels). The amount of polyethylene glycol was shown to be the
      factor that had the greatest influence on the encapsulation efficiency (evaluated
      response) at 95% confidence level. Some properties of nanoparticles like process
      yield, drug-polymer interaction, particle morphology, and in vitro dissolution
      profile, which could affect biological performance, have also been evaluated. 

PMID- 24092972
TI  - Design, characterization, and aerosolization of organic solution advanced spray
      dried moxifloxacin and ofloxacin dipalmitoylphosphatidylcholine (DPPC)
      microparticulate/nanoparticulate powders for pulmonary inhalation aerosol
      delivery.
AB  - The aim of this study was to design and develop respirable antibiotics
      moxifloxacin (MOXI) hydrochloride and ofloxacin (OFLX) microparticles and
      nanoparticles, and multifunctional antibiotics particles with or without lung
      surfactant 1,2-dipalmitoyl-sn-glycero-3-phosphocholine (DPPC) for targeted dry
      powder inhalation delivery as a pulmonary nanomedicine. Particles were rationally
      designed and produced by advanced spray-drying particle engineering from an
      organic solution in closed mode (no water) from dilute solution. Scanning
      electron microscopy indicated that these particles had both optimal particle
      morphology and surface morphology, and the particle size distributions were
      suitable for pulmonary delivery. Comprehensive and systematic physicochemical
      characterization and in vitro aerosol dispersion performance revealed significant
      differences between these two fluoroquinolone antibiotics following spray drying
      as drug aerosols and as cospray-dried antibiotic drug: DPPC aerosols. Fourier
      transform infrared spectroscopy and confocal Raman microspectroscopy were
      employed to probe composition and interactions in the solid state. Spray-dried
      MOXI was rendered noncrystalline (amorphous) following organic solution advanced
      spray drying. This was in contrast to spray-dried OFLX, which retained partial
      crystallinity, as did OFLX:DPPC powders at certain compositions. Aerosol
      dispersion performance was conducted using inertial impaction with a dry powder
      inhaler device approved for human use. The present study demonstrates that the
      use of DPPC offers improved aerosol delivery of MOXI as cospray-dried
      microparticulate/nanoparticulate powders, whereas residual partial crystallinity
      influenced aerosol dispersion of OFLX and most of the compositions of OFLX:DPPC
      inhalation powders. 

PMID- 24092973
TI  - Synthesis, characterization, and efficacy of antimicrobial chlorhexidine
      hexametaphosphate nanoparticles for applications in biomedical materials and
      consumer products.
AB  - Chlorhexidine (CHX) is an antimicrobial agent that is efficacious against gram
      negative and -positive bacteria and yeasts. Its mechanism of action is based on
      cell membrane disruption and, as such, it does not promote the development of
      bacterial resistance, which is associated with the widespread use of antibiotics.
      In this manuscript, we report the development of novel antimicrobial
      nanoparticles (NPs) based on a hexametaphosphate salt of CHX. These are
      synthesized by instantaneous reaction between equimolar aqueous solutions of CHX
      digluconate and sodium hexametaphosphate, under room temperature and pressure.
      The reaction results in a stable colloid composed of highly negatively charged
      NPs (-50 mV), of size 20-160 nm. The NPs adhere rapidly to specimens of glass,
      titanium, and an elastomeric wound dressing, in a dose-dependent manner. The
      functionalized materials exhibit a gradual leaching of soluble CHX over a period
      of at least 50 days. The NP colloid is efficacious against methicillin-resistant
      Staphylococcus aureus (MRSA) and Pseudomonas aeruginosa in both planktonic and
      biofilm conditions. These NPs may find application in a range of biomedical and
      consumer materials. 

PMID- 24092974
TI  - Multinucleation and cell dysfunction induced by amorphous silica nanoparticles in
      an L-02 human hepatic cell line.
AB  - Silica nanoparticles (SNPs) are one of the most important nanomaterials, and have
      been widely used in a variety of fields. Therefore, their effects on human health
      and the environment have been addressed in a number of studies. In this work, the
      effects of amorphous SNPs were investigated with regard to multinucleation in L
      02 human hepatic cells. Our results show that L-02 cells had an abnormally high
      incidence of multinucleation upon exposure to silica, that increased in a dose
      dependent manner. Propidium iodide staining showed that multinucleated cells were
      arrested in G2/M phase of the cell cycle. Increased multinucleation in L-02 cells
      was associated with increased generation of cellular reactive oxygen species and
      mitochondrial damage on flow cytometry and confocal microscopy, which might have
      led to failure of cytokinesis in these cells. Further, SNPs inhibited cell growth
      and induced apoptosis in exposed cells. Taken together, our findings demonstrate
      that multinucleation in L-02 human hepatic cells might be a failure to undergo
      cytokinesis or cell fusion in response to SNPs, and the increase in cellular
      reactive oxygen species could be responsible for the apoptosis seen in both
      mononuclear cells and multinucleated cells. 

PMID- 24092975
TI  - Enhanced and sustained topical ocular delivery of cyclosporine A in
      thermosensitive hyaluronic acid-based in situ forming microgels.
AB  - For nearly a decade, thermoresponsive ophthalmic in situ gels have been
      recognized as an interesting and promising ocular topical delivery vehicle for
      lipophilic drugs. In this study, a series of thermosensitive copolymers,
      hyaluronic acid-g-poly(N-isopropylacrylamide) (HA-g-PNIPAAm), was synthesized, by
      coupling carboxylic end-capped PNIPAAm to aminated hyaluronic acid through amide
      bond linkages, and was used as a potential carrier for the topical ocular
      administration of cyclosporine A (CyA). The lower critical solution temperature
      of HA-g-PNIPAAm59 in aqueous solutions was measured as 32.7 degrees C, which was
      not significantly affected by the polymer concentration. Moreover, HA-g-PNIPAAm59
      microgels showed a high drug loading efficiency (73.92%) and a controlled release
      profile that are necessary for biomedical application. Transmission electron
      microscopy (TEM) and atomic force microscopy (AFM) observations showed that HA-g
      PNIPAAm microgels were spherical in shape with homogeneous size. Based on the
      result of the eye irritation test, the HA-g-PNIPAAm microgels formulation was
      shown to be safe and nonirritant for rabbit eyes. In addition, HA-g-PNIPAAm
      microgels achieved significantly higher CyA concentration levels in rabbit
      corneas (1455.8 ng/g of tissue) than both castor oil formulation and commercial
      CyA eye drops. Therefore, these newly described thermoresponsive HA-g-PNIPAAm
      microgels demonstrated attractive properties to serve as pharmaceutical delivery
      vehicles for a variety of ophthalmic applications. 

PMID- 24092976
TI  - Confusion assessment method: a systematic review and meta-analysis of diagnostic
      accuracy.
AB  - BACKGROUND: Delirium is common in the early stages of hospitalization for a
      variety of acute and chronic diseases. OBJECTIVES: To evaluate the diagnostic
      accuracy of two delirium screening tools, the Confusion Assessment Method (CAM)
      and the Confusion Assessment Method for the Intensive Care Unit (CAM-ICU).
      METHODS: We searched MEDLINE, EMBASE, and PsychInfo for relevant articles
      published in English up to March 2013. We compared two screening tools to
      Diagnostic and Statistical Manual of Mental Disorders IV criteria. Two reviewers
      independently assessed studies to determine their eligibility, validity, and
      quality. Sensitivity and specificity were calculated using a bivariate model.
      RESULTS: Twenty-two studies (n = 2,442 patients) met the inclusion criteria. All
      studies demonstrated that these two scales can be administered within ten
      minutes, by trained clinical or research staff. The pooled sensitivities and
      specificity for CAM were 82% (95% confidence interval [CI]: 69%-91%) and 99% (95%
      CI: 87%-100%), and 81% (95% CI: 57%-93%) and 98% (95% CI: 86%-100%) for CAM-ICU,
      respectively. CONCLUSION: Both CAM and CAM-ICU are validated instruments for the
      diagnosis of delirium in a variety of medical settings. However, CAM and CAM-ICU
      both present higher specificity than sensitivity. Therefore, the use of these
      tools should not replace clinical judgment.

PMID- 24092977
TI  - Incidence and time course of extrapyramidal symptoms with oral and long-acting
      injectable paliperidone: a posthoc pooled analysis of seven randomized controlled
      studies.
AB  - BACKGROUND: The purpose of this study was to compare incidence rates and time
      course of extrapyramidal symptom (EPS)-related treatment-emergent adverse events
      (TEAEs) between oral and long-acting injectable (LAI) paliperidone. METHODS: The
      analysis included pooled data (safety analysis set, 2,256 antipsychotic-treated
      and 865 placebo-treated patients with schizophrenia) from seven randomized,
      double-blind, placebo-controlled paliperidone studies (three oral [6 weeks each]
      and four LAI [9-13 weeks]) and assessed comparable doses (oral, 3-15 mg; LAI, 25
      150 mg eq. [US doses 39-234 mg]). We summarized incidence rates and time of onset
      for EPS-related TEAE, categorized by EPS group terms, ie, tremor, dystonia,
      hyperkinesia, parkinsonism, and dyskinesia, and use of anti-EPS medication. Mean
      scores over time for the Abnormal Involuntary Movement Scale (AIMS, for
      dyskinesia), Barnes Akathisia Rating Scale (BARS, for akathisia), and Simpson
      Angus Rating Scale (SAS, for parkinsonism) were graphed. RESULTS: Incidence rates
      for all categories of spontaneously reported EPS-related TEAEs except for
      hyperkinesia, were numerically lower in pooled LAI studies than in pooled oral
      studies. Highest rates were observed in the first week of paliperidone-LAI (for
      all EPS symptoms except dyskinesia) and oral paliperidone treatment (except
      parkinsonism and tremor). Anti-EPS medication use was significantly lower in LAI
      (12%) versus oral studies (17%, P = 0.0035). Mean values for EPS scale scores
      were similar between LAI and oral treatment at endpoint, and no dose response was
      evident. Mean reductions (standard deviation) from baseline to endpoint in EPS
      scale scores were larger for LAI (AIMS, -0.10 [1.27]; BARS, -0.09 [1.06]; SAS, 
      0.04 [0.20]) versus oral studies (AIMS, -0.08 [1.32]; BARS, -0.03 [1.24]; SAS,
      0.0 [0.23]). These changes favored LAI for BARS (P = 0.023) and SAS (P < 0.0001),
      but not for AIMS (P = 0.49), at endpoint for the studies. CONCLUSION: In this
      posthoc descriptive analysis, incidence rates of spontaneously reported EPS
      related TEAEs were numerically lower following approximately 90 days of exposure
      with LAI and approximately 40 days with oral paliperidone at comparable doses.

PMID- 24092978
TI  - Domperidone effective in preventing rivastigmine-related gastrointestinal
      disturbances in patients with Alzheimer's disease.
AB  - OBJECTIVE: While acetylcholinesterase inhibitors, such as donepezil, galantamine,
      and rivastig-mine, are beneficial in treating behavioral symptoms of patients
      with Alzheimer's disease (AD), their dose-limiting effects include
      gastrointestinal disturbances, such as nausea, vomiting, and diarrhea. We aimed
      to predict the occurrence of these gastrointestinal disturbances with
      rivastigmine therapy for optimal drug choice and improved compliance. MATERIALS
      AND METHODS: Thirty patients with mild-to-moderate AD (scores 10-22 on the
      MiniMental State Examination) were administered a rivastigmine 18 mg patch with
      domperidone 30 mg (RWD) and without domperidone (RWOD; n = 15 each) for 20 weeks.
      Gastrointestinal disturbances were evaluated using a frequency scale for symptoms
      of gastroesophageal reflux disease (FSSG), Bristol stool form scale, laboratory
      data (hemoglobin, albumin, total cholesterol), body weight, and amount of food
      intake. RESULTS: After 12 weeks, FSSG scores were higher in the RWOD group
      compared to baseline scores; however, no significant differences were noted
      between the RWD and RWOD groups. We then subdivided each group based on high and
      low baseline scores; the RWOD high-score (>=4) subgroup showed increased FSSG
      after 12 weeks compared with the baseline score. In both RWD and RWOD groups, the
      low-score (<=3) subgroups showed no changes during the dose-escalation phase.
      CONCLUSION: For AD patients with higher FSSG scores at baseline, domperidone was
      effective in preventing rivastigmine-related gastrointestinal disturbances.

PMID- 24092980
TI  - The Impact of Event Scale - Revised: psychometric properties of the Italian
      version in a sample of flood victims.
AB  - BACKGROUND: This study aims to verify the main psychometric properties of the
      Italian version of the Impact of Event Scale - Revised (IES-R) in a sample of
      flood victims. METHODS: The sample was composed of 262 subjects involved in the
      natural disaster of 2009 in the city of Messina (Italy). All participants
      completed the IES-R and the Dissociative Experiences Scale-II (DES-II) in order
      to verify some aspects of convergent validity. RESULTS: THE EXPLORATORY AND
      CONFIRMATORY FACTOR ANALYSIS, USED TO VERIFY THE CONSTRUCT VALIDITY OF THE
      MEASURE, SHOWED A CLEAR FACTOR STRUCTURE WITH THREE INDEPENDENT DIMENSIONS:
      intrusion, avoidance, and hyper-arousal. The goodness-of-fit indices (non-normed
      fit index [NNFI] = 0.99; comparative fit index [CFI] = 0.99; standardized root
      mean square residual [SRMR] = 0.04; and root mean square error of approximation
      [RMSEA] = 0.02) indicated a good adaptation of the model to the data. The IES-R
      scales showed satisfactory values of internal consistency (intrusion, alpha =
      0.78; avoidance, alpha = 0.72; hyper-arousal, alpha = 0.83) and acceptable values
      of correlation with the DES-II. CONCLUSION: These results suggest that this self
      reported and easily administered instrument for assessing the dimensions of
      trauma has good psychometric properties and can be adopted usefully, both for
      research and for practice in Italy.

PMID- 24092979
TI  - Childhood depression: a systematic review.
AB  - As an important public health issue, childhood depression deserves special
      attention, considering the serious and lasting consequences of the disease to
      child development. Taking this into consideration, the present study was based on
      the following question: what practical contributions to clinicians and
      researchers does the current literature on childhood depression have to offer?
      The objective of the present study was to conduct a systematic review of articles
      regarding childhood depression. To accomplish this purpose, a systematic review
      of articles on childhood depression, published from January 1, 2010 to November
      24, 2012, on MEDLINE and SciELO databases was carried out. Search terms were
      "depression" (medical subject headings [MeSH]), "child" (MeSH), and "childhood
      depression" (keyword). Of the 180 retrieved studies, 25 met the eligibility
      criteria. Retrieved studies covered a wide range of aspects regarding childhood
      depression, such as diagnosis, treatment, prevention and prognosis. Recent
      scientific literature regarding childhood depression converge to, directly or
      indirectly, highlight the negative impacts of depressive disorders to the
      children's quality of life. Unfortunately, the retrieved studies show that
      childhood depression commonly grows in a background of vulnerability and poverty,
      where individual and familiar needs concerning childhood depression are not
      always taken into consideration. In this context, this review demonstrated that
      childhood-onset depression commonly leads to other psychiatric disorders and co
      morbidities. Many of the retrieved studies also confirmed the hypothesis that
      human resources (eg, health care team in general) are not yet adequately trained
      to address childhood depression. Thus, further research on the development of
      programs to prepare health care professionals to deal with childhood depression
      is needed, as well as complementary studies, with larger and more homogeneous
      samples, centered on prevention and treatment of childhood depression. 

PMID- 24092981
TI  - Psychomotor approach in children affected by nonretentive fecal soiling (FNRFS):
      a new rehabilitative purpose.
AB  - BACKGROUND: According to the Rome III criteria, encopresis without constipation
      was defined as nonretentive fecal soiling (FNRFS) with not yet well understood
      etiology. Treatment approaches reported in the literature with varying results
      include biofeedback, hypnosis, reflexology, and Internet-based educational
      programs. In developmental age, another behavioral treatment could be identified
      in the psychomotor approach, which is called psychomotricity in the European
      countries, or is also known as play therapy. The aim of the present study was to
      verify the safety and efficacy of play therapy plus toilet training in a small
      sample of prepubertal children affected by FNRFS. MATERIALS AND METHODS: Twenty
      six patients (group 1; 16 males, mean age of 5.92 +/- 0.84 years) underwent a
      psychomotor approach therapy program in association with toilet training for 6
      months, and the other 26 subjects (group 2; 17 males, mean age of 5.76 +/- 0.69)
      underwent the sole toilet training program for 6 months. During the observational
      time period (T0) and after 6 months (T1) of both treatments, the patients were
      evaluated for FNRFS frequency and for the behavioral assessment. RESULTS: At T0,
      the FNRFS mean frequency per month for group 1 was 20.115 episodes/month
      (standard deviation [SD] +/- 3.024) and for group 2 was 20.423 (SD +/- 1.879) (P
      = 0.661). At T1 the mean frequency per month was 6.461 (SD +/- 1.333)
      episodes/month and 12.038 (SD +/- 1.341), respectively (P < 0.001). Moreover, the
      delta percent average of the frequency between T0 and T1 was 67.121 +/- 8.527 for
      group 1 and 40.518 +/- 9.259 for group 2 (P < 0.001). At T1, a significant
      improvement in scores on the behavioral scale was identified. CONCLUSION: Our
      preliminary results show the importance of a multidisciplinary approach, and
      suggest the positive effect of an additional psychomotor approach, as this holds
      a new and interesting rehabilitative purpose for children in a toilet training
      program, even if further research is necessary.

PMID- 24092983
TI  - Persisting primitive reflexes in medication-naive girls with attention-deficit
      and hyperactivity disorder.
AB  - BACKGROUND AND OBJECTIVES: Recent and historical findings suggest that later
      developed functions during brain ontogenesis related to higher levels of
      cognitive and motor integration tend to replace the older, more primitive, ones,
      and the persistence of the older functions may be linked to specific
      neuropsychiatric disorders. Currently, there is growing evidence to suggest that
      persisting primitive reflexes may be related to developmental and
      neurodegenerative disorders. Preliminary data also suggest that persisting
      primitive reflexes may be specifically linked to attention-deficit and
      hyperactivity disorder (ADHD). METHODS: In the study reported here, we tested to
      what extent the persisting primitive asymmetric tonic neck reflex and symmetric
      tonic neck reflex are related to ADHD symptoms measured by Conners' Parent
      Questionnaire in 35 medication-naive girls of school age (8-11 years) with ADHD.
      The results were compared with those of a control group of 30 girls of the same
      age. RESULTS: This study showed that persisting primitive reflexes are closely
      linked to ADHD symptoms. CONCLUSION: The data suggest that ADHD symptoms may be
      linked to more primitive neural mechanisms interfering with higher brain
      functions due to insufficiently developed cognitive and motor integration.

PMID- 24092984
TI  - Changes in post traumatic stress symptoms among women in substance use disorder
      treatment: the mediating role of bodily dissociation and emotion regulation.
AB  - Individuals in substance use disorder (SUD) treatment have shown high levels of
      difficulty with emotion regulation, as well as a high prevalence of reported
      trauma and symptoms of post-traumatic stress (PTS). Dissociation from the body is
      a common clinical experience among women with a history of sexual trauma.
      Research has shown promising effects of mind-body approaches in SUD treatment, as
      well as the importance of emotional regulation in conceptual models of
      psychopathology. The current study examines the mediating role of bodily
      dissociation and emotion regulation on PTS symptoms in a sample of women enrolled
      in substance use disorder treatment. Results indicate that bodily dissociation
      and emotion regulation had significant direct effects on PTS symptoms from
      baseline to a 6-month follow-up, and that bodily dissociation also may indirectly
      operate to reduce PTS symptoms through its effect on emotion regulation
      difficulties. These results suggest the importance of addressing bodily
      dissociation and emotion regulation difficulties in women's substance use
      disorder treatment. 

PMID- 24092982
TI  - Behavioral symptoms related to cognitive impairment.
AB  - Neuropsychiatric symptoms (NPS) are core features of Alzheimer's disease and
      related dementias. On one hand, behavioral symptoms in patients with mild
      cognitive impairment (MCI) can indicate an increased risk of progressing to
      dementia. On the other hand, mild behavioral impairment (MBI) in patients who
      usually have normal cognition indicates an increased risk of developing dementia.
      Whatever the cause, all dementias carry a high rate of NPI. These symptoms can be
      observed at any stage of the disease, may fluctuate over its course, are a
      leading cause of stress and overload for caregivers, and increase rates of
      hospitalization and early institutionalization for patients with dementia. The
      clinician should be able to promptly recognize NPI through the use of instruments
      capable of measuring their frequency and severity to support diagnosis, and to
      help monitor the treatment of behavioral symptoms. The aims of this review are to
      describe and update the construct 'MBI' and to revise the reported NPS related to
      prodromal stages of dementia (MCI and MBI) and dementia stages of Alzheimer's
      disease and frontotemporal lobar degeneration. 

PMID- 24092985
TI  - A simplified method for routine outcome monitoring after drug abuse treatment.
AB  - THE ROUTINE COLLECTION OF DRUG TREATMENT OUTCOMES TO MANAGE QUALITY OF CARE,
      IMPROVE PATIENT SATISFACTION, AND ALLOCATE TREATMENT RESOURCES IS CURRENTLY
      HAMPERED BY TWO KEY DIFFICULTIES: (1) problems locating clients once they leave
      treatment; and (2) the prohibitive cost of obtaining meaningful and reliable post
      treatment data. This pilot describes precise methods for an economical staff
      based routine outcome monitoring (ROM) system using an 18-item core measure
      telephone survey. As implemented at NarcononTM of Oklahoma, a behavioral and
      social skills based, residential drug rehabilitation program, the system was
      psychometrically adequate for aggregate reporting while providing clinically
      useful information. Standardized procedures for staff training, collecting client
      contact information, structuring exit interviews and maintaining post-treatment
      telephone contact produced follow-up rates that improved from 57.6% to 100% over
      the course of the project. Aggregate data was used to improve program delivery
      and thereby post-treatment substance use and social outcomes. These methods and
      use of data may contribute to the discussion on how to best monitor outcomes. 

PMID- 24092987
TI  - Effects of tranilast on the urinary excretion of kynurenic and quinolinic Acid
      under conditions of L tryptophan loading.
AB  - The pathogenesis of morphea and other cutaneous sclerosing disorders remain
      poorly understood. Although they are considered to be autoimmune disorders,
      abnormal tryptophan metabolism may be involved. Current therapy is directed to
      supressing the autoimmune response. Demonstration of a therapeutic response to
      manipulation of the kynurenine pathway would both support a role for abnormal
      tryptophan metabolism and offer additional targets for therapy. Tranilast is a 3
      hydroxyanthranilic acid derivative known to target the kynurenine pathway. The
      aim of this study was to see if tranilast lowered the urinary excretion of the
      kynurenine metabolites kynurenic and quinolinic acid under condition of L
      tryptophan loading in a volunteer. Mean baseline value for kynurenic acid and
      quinolinic acid were 1.1 and 2.1 mmol/mol creatinine, respectively. This rose to
      5.6 and 3.8 mmol/mol creatinine respectively under conditions of L tryptophan
      loading 2 grams daily. Adding 1 g of tranilast daily lowered the values to 2.0
      and 2.9 mmol/mol creatinine, respectively. These data suggest that tranilast acts
      as a competitive inhibitor of either indoleamine 2, 3-dioxygenase (IDO),
      tryptophan 2, 3-di-oxygenase (TDO) or both. As it involved only 1 subject, the
      results may not be representative of the larger population and must be considered
      preliminary. 

PMID- 24092986
TI  - The kynurenine pathway in stem cell biology.
AB  - The kynurenine pathway (KP) is the main catabolic pathway of the essential amino
      acid tryptophan. The KP has been identified to play a critical role in regulating
      immune responses in a variety of experimental settings. It is also known to be
      involved in several neuroinflammatory diseases including Huntington's disease,
      amyotrophic lateral sclerosis, and Alzheimer's disease. This review considers the
      current understanding of the role of the KP in stem cell biology. Both of these
      fundamental areas of cell biology have independently been the focus of a
      burgeoning research interest in recent years. A systematic review of how the two
      interact has not yet been conducted. Several inflammatory and infectious diseases
      in which the KP has been implicated include those for which stem cell therapies
      are being actively explored at a clinical level. Therefore, it is highly relevant
      to consider the evidence showing that the KP influences stem cell biology and
      impacts the functional behavior of progenitor cells. 

PMID- 24092988
TI  - Expression and prognostic relevance of MET and phospho-BAD in non-small cell lung
      cancer.
AB  - BACKGROUND: MET is involved in the progression of several types of human cancers,
      while phospho-BAD(Ser-136) is a key molecule in apoptosis and might be regulated
      by MET. The aim of this study was to investigate the correlation between altered
      expression of MET and phospho-BAD in non-small cell lung cancer (NSCLC) and their
      association with clinicopathologic parameters and overall survival. METHODS: MET
      and phospho-BAD(Ser-136) proteins were evaluated by immunohistochemical analysis
      in 183 paraffin-embedded specimens and were also assessed by Western blotting
      analysis in 12 frozen tumor tissue samples, which were representative examples of
      immunohistochemical staining. RESULTS: Positive expression of MET and phospho
      BAD(Ser-136) occurred in 67.2% and 49.2% of the 183 cases of NSCLC, respectively.
      However, neither MET expression nor phospho-BAD(Ser-136) expression was
      associated with any clinicopathologic parameter. A significant correlation was
      found between MET and phospho-BAD(Ser-136) expression levels evaluated by
      immunohistochemistry (r = 0.268, P < 0.001). Overexpression of MET was
      significantly associated with shortened overall survival in univariate analysis
      (P < 0.001). Moreover, patients with a MET+/phospho-BAD(Ser-136)+ phenotype had a
      poorer prognosis than others (P < 0.001). Multivariate Cox proportional hazard
      analysis confirmed that MET expression is a prognostic factor for NSCLC.
      CONCLUSION: MET expression might be correlated with phospho-BAD(Ser-136)
      expression, and may be an adverse predictor for NSCLC. Activation of the
      MET/phospho-BAD(Ser-136) signaling pathway might play a role in the development
      and progression of NSCLC.

PMID- 24092990
TI  - Resveratrol decreases B-cell lymphoma-2 expression and viability in GH3 pituitary
      adenoma cells of the rat.
AB  - OBJECTIVE: Resveratrol is a phytoestrogen with various antiproliferative and
      proapoptotic effects. This in vitro study aimed to analyze the effect of
      resveratrol on the viability and expression of modulators of apoptosis in GH3
      pituitary adenoma cells of the rat. METHODS: GH3 cells were incubated with
      resveratrol concentrations from 20 to 100 MUM for 48-72 hours. Cell viability was
      quantified using a hemocytometer. We assessed the ability of resveratrol to kill
      GH3 cells by an enzyme-linked immunosorbent assay (ELISA) of nucleosome
      liberation and by DNA degradation (unidimensional gel electrophoresis). Relative
      messenger RNA (mRNA) expression of survivin, B-cell lymphoma-2 protein (BCL-2)
      and BCL-2-associated X protein (BAX) normalized to beta2 microglobulin was
      measured using quantitative real-time polymerase chain reaction (qRT-PCR).
      RESULTS: GH3 cell survival significantly decreased with increasing concentrations
      of resveratrol. In GH3 cells treated with 100 MUM resveratrol, ELISA demonstrated
      a significant rise of nucleosome liberation, which typically occurs during
      apoptosis. In parallel, gel electrophoresis showed degradation of DNA into random
      fragments, pointing to a necrotic mode of cell death in most GH3 cells. In GH3
      cells treated with 100 MUM resveratrol, qRT-PCR detected a significant decrease
      of BCL-2 mRNA expression and a decrease of survivin mRNA expression, whereas a
      change of BAX mRNA expression could not be found. The BAX/BCL-2 ratio was
      significantly increased in GH3 cells after resveratrol treatment. CONCLUSIONS:
      Resveratrol reduces GH3 cell viability in a dose-dependent manner by inducing
      nonapoptotic cell death and apoptosis. Apoptosis in GH3 cells is probably
      mediated by resveratrol-dependent downregulation of apoptosis inhibitors, namely
      BCL-2 and possibly survivin. Further investigation of the potential effects of
      resveratrol on pituitary adenoma cells is warranted.

PMID- 24092989
TI  - The role of chemotherapy and latest emerging target therapies in anaplastic
      thyroid cancer.
AB  - Anaplastic thyroid cancer represents 1%-2% of thyroid cancers. For its
      aggressiveness, it is considered a systemic disease at the time of diagnosis.
      Surgery remains the cornerstone of therapy in resectable tumor. Traditional
      chemotherapy has little effect on metastatic disease. A multimodality approach,
      incorporating cytoreductive surgical resection, chemoradiation, either
      concurrently or sequentially, and new promising target therapies is advisable.
      Doxorubicin is the most commonly used agent, with a response rate of 22%.
      Recently, other chemotherapy agents have been used, such as paclitaxel and
      gemcitabine, with superimposable activity and response rates of 10%-20%. However,
      survival of patients with anaplastic thyroid cancer has changed little in the
      past 50 years, despite more aggressive systemic and radiotherapies. Several new
      agents are currently under investigation. Some of them, such as sorafenib,
      imatinib, and axitinib have been tested in small clinical trials, showing
      promising disease control rates ranging from 35%-75%. Referral of patients for
      participation in clinical trials is needed. 

PMID- 24092991
TI  - Impact of age on functional exercise correlates in patients with advanced lung
      cancer.
AB  - BACKGROUND: The functional exercise capacity and its correlates in advanced
      cancer patients in stratified age groups were examined. MATERIALS AND METHODS: A
      total of 105 patients with advanced lung cancer were recruited prospectively and
      stratified into young (<=50 years), middle (51-65 years), and old (>65 years) age
      groups. Respiratory performances, which included maximal inspiratory and
      expiratory pressure, forced expiratory volume in 1 second, and forced vital
      capacity were measured. The distance ambulated in a 6-minute walk test was used
      as an indicator for functional capacity. RESULTS: The young age group had lowest
      baseline pulmonary function and performed worse on the 6-minute walk test among
      the three age groups. The risk factors for poor functional capacity were female,
      lower percent predicted maximal expiratory pressure, worse dyspnea, and lower
      hemoglobin in the young age group; lower percent predicated forced expiratory
      volume in 1 second and forced vital capacity, and greater weight loss in the
      middle age group; and only worse dyspnea in the old age group. The above
      identified risk factors accounted for 73.6%, 58.5%, and 42.1% variance in 6
      minute walk distance for the young, middle, and old age group, respectively.
      CONCLUSION: The impacts of these factors on functional exercise capacity should
      be carefully considered while designing exercise intervention according to age.

PMID- 24092993
TI  - Overall survival and disease-free survival in endometrial cancer: prognostic
      factors in 276 patients.
AB  - OBJECTIVE: The aim of the study reported here was to assess the disease-free
      survival and overall survival of patients with endometrial cancer and to
      determine independent factors affecting the prognosis. MATERIALS AND METHODS:
      This was a retrospective study of a single-center clinical series of 276 patients
      (mean age 64 years) with histologically confirmed cancer of the corpus uteri. The
      standard treatments were extrafascial total hysterectomy and bilateral salpingo
      oophorectomy with selective pelvic/para-aortic node dissection, according to risk
      for recurrence. Actuarial overall survival and disease-free survival were
      estimated according to the Kaplan-Meier method. Univariate and multivariate Cox
      proportional hazards analyses were used to assess the prognostic significance of
      the different variables. RESULTS: The estimated median follow-up, determined
      using the inverse Kaplan-Meier method, was 45 months (95% confidence interval
      [CI] 41.2-48.8) for disease-free survival and 46 months (95% CI 43.0-49.0) for
      overall survival. The statistically significant variables affecting disease-free
      survival and overall survival were age, serous-papillary and clear-cell
      histological types, outer-half myometrial invasion, advanced International
      Federation of Gynecology and Obstetrics (FIGO) stage, tumor grades G2 and G3,
      incomplete surgical resection, positive lymph nodes, lymphovascular space
      invasion, tumor remnants of >1 cm after surgery, and high-risk group. In the
      multivariate Cox regression model, predictors of tumor recurrence included
      advanced FIGO stage (hazard ratio [HR] 4.90, 95% CI 2.57-9.36, P < 0.001) and
      tumor grades G2 (HR 4.79, 95% CI 1.73-13.27, P = 0.003) and G3 (HR 7.56, 95% CI
      2.75-20.73, P < 0.001). The same variables were also associated with a
      significantly higher risk of tumor-related mortality. CONCLUSION: FIGO stage and
      tumor grade were independent prognostic factors of disease-free survival and
      overall survival in endometrial cancer patients. Outcome was also influenced by
      histopathologic type, myometrial and lymphovascular space invasion, lymph-node
      involvement, age, and tumor remnants after surgery, although a larger study
      sample is probably needed to demonstrate the independent association of these
      variables with survival.

PMID- 24092994
TI  - The impact of patients' chronic disease on family quality of life: an experience
      from 26 specialties.
AB  - BACKGROUND: Previous studies have assessed family quality of life in individual
      disease areas and specialties. The aim of this study was to investigate the
      impact of disease on family members of patients over a wide range of specialties
      and identify key impact areas. This information is essential in order to reveal
      the extent of this impact and to allow strategies to be developed to support the
      family members of patients with chronic disease. METHODS: Semi-structured
      interviews were carried out with 133 family members of mostly chronically ill
      patients from 26 medical specialties. Family members were invited to discuss all
      areas of their lives that had been affected by having an unwell relative.
      Thematic analysis was carried out using NVivo9(r) software. RESULTS: Most family
      members were female (61%), the partner or spouse of the patient (56%), or the
      parent (22%). Their mean age was 56.1 years (range: 21-85 years) and the mean
      duration of the patient's disease was 8.9 years (range: 1 month to 60 years). Ten
      key themes of family quality of life were identified from interviews. The median
      number of themes reported by family members was six (range: 1-10). The key themes
      included: emotional impact (mentioned by 92% of subjects), daily activities
      (91%), family relationships (69%), sleep and health (67%), holidays (62%),
      involvement in medical care and support given to family members (61%), work and
      study (52%), financial impact (51%), social life (37%), and time planning (14%).
      Relationships between the themes were identified. CONCLUSION: This large scale
      multi-specialty study has demonstrated the significant, yet similar, impact that
      illness can have on the quality of life of patients' family members. Family
      quality of life is a previously neglected area of health care which needs to be
      addressed in order to provide appropriate support for the patient and the family
      unit.

PMID- 24092995
TI  - Diabetic retinopathy is associated with oxidative stress and mitigation of gene
      expression of antioxidant enzymes.
AB  - Type 2 diabetes is a metabolic disease associated with serious complications,
      including diabetic retinopathy (DR). The authors' main aim was to investigate
      biochemical parameters and the oxidative stress associated with the type 2 DR
      patients and to study gene expression of superoxide dismutase (SOD), catalase
      (CAT), and glutathione peroxidase (GPx) among patients with DR [DR(+)] compared
      with a control nondiabetic group. In all, 67 patients with DR included in this
      study were diabetic for more than 10 years. Among them, 22 patients were DR(+),
      and 45 patients did not have DR [DR(-)]. The subjects' age range was 14 years to
      80 years old with diabetes duration range between 2 and 45 years. Body mass index
      (BMI) was 31.43 +/- 5.94 and 32.33 +/- 6.54, systolic blood pressure was 117.15
      +/- 18.16 mmHg and 126.15 +/- 20.26 mmHg, diastolic blood pressure was 81.11 +/-
      10.55 mmHg and 82.77 +/- 10.85 mmHg, HbA1c was 7.2 +/- 1.1 and 8.19 +/- 1.95,
      serum total cholesterol was 6.61 +/- 1.11 and 4.11 +/- 0.31, serum triglycerides
      were 3.52 +/- 0.89 and 3.42 +/- 0.79, serum low-density lipoprotein (LDL) was
      2.12 +/- 0.10 and 2.42 +/- 0.15, high-density lipoprotein (HDL) was 2.66 +/- 0.30
      and 2.55 +/- 0.21, SOD was 3.12 +/- 0.87 and 1.53 +/- 0.14, GPx was 11.14 +/-
      2.21 and 8.2 +/- 1.84, CAT was 26.43 +/- 3.34 and 9.60 +/- 2.14, for DR(-) and
      DR(+) patients, respectively. SOD, GPx and CAT polymerase chain reaction (PCR)
      products of the DR(+) patients revealed the diminished expression of CAT gene
      followed by GPx and SOD genes. All were significant compared with the normal
      controls, P < 0.05. Linear regression analysis revealed a strong significant
      positive correlation between the retinopathy grade and the diastolic blood
      pressure, diabetes duration, hemoglobin A1c (HA1c)%, and fasting blood glucose (P
      < 0.001). A marginally significant positive correlation between the retinopathy
      grade and LDL-cholesterol was observed (P < 0.05), and a significant negative
      correlation between the retinopathy grade and total cholesterol was observed (P <
      0.05). Poor glycemic control and alteration in mRNA gene expression of
      antioxidant enzymes are strongly associated with development of DR and the
      regular screening is mandatory for early detection and treatment. 

PMID- 24092992
TI  - IAP proteins as targets for drug development in oncology.
AB  - The inhibitors of apoptosis (IAPs) constitute a family of proteins involved in
      the regulation of various cellular processes, including cell death, immune and
      inflammatory responses, cell proliferation, cell differentiation, and cell
      motility. There is accumulating evidence supporting IAP-targeting in tumors: IAPs
      regulate various cellular processes that contribute to tumor development, such as
      cell death, cell proliferation, and cell migration; their expression is increased
      in a number of human tumor samples, and IAP overexpression has been correlated
      with tumor growth, and poor prognosis or low response to treatment; and IAP
      expression can be rapidly induced in response to chemotherapy or radiotherapy
      because of the presence of an internal ribosome entry site (IRES)-dependent
      mechanism of translation initiation, which could contribute to resistance to
      antitumor therapy. The development of IAP antagonists is an important challenge
      and was subject to intense research over the past decade. Six molecules are
      currently in clinical trials. This review focuses on the role of IAPs in tumors
      and the development of IAP-targeting molecules for anticancer therapy. 

PMID- 24092996
TI  - Population-based study of central post-stroke pain in Rimini district, Italy.
AB  - Central post-stroke pain (CPSP) is still an underestimated complication of
      stroke, resulting in impaired quality of life and, in addition to the functional
      and cognitive consequences of stroke, the presence of CPSP may be associated with
      mood disorders, such as depression, anxiety, and sleep disturbances. This type of
      pain may also impair activities of daily living and further worsen quality of
      life, negatively influencing the rehabilitation process. The prevalence of CSPS
      in the literature is highly variable (1%-12%) according to different studies, and
      this variability could be influenced by selection criteria and the different
      ethnic populations being investigated. With this scenario in mind, we performed a
      population-based study to assess the prevalence of CPSP and its main features in
      a homogeneous health district (Rimini, Italy), including five hospitals for a
      total population of 329,970 inhabitants. From 2008 to 2010, we selected 1,494
      post-stroke patients and were able to interview 660 patients, 66 (11%) of whom
      reported pain with related tactile and thermal hyperesthesia, accompanied by
      needle puncture, tingling, swelling, and pressure sensations. Patients reported
      motor impairment and disability, which influenced their working ability,
      rehabilitation, and social life. Despite this severe pain state, there was a high
      percentage of patients who did not receive adequate treatment for pain. 

PMID- 24092998
TI  - Clinical and radiographic outcomes with L4-S1 axial lumbar interbody fusion
      (AxiaLIF) and posterior instrumentation: a multicenter study.
AB  - INTRODUCTION: Previous studies have confirmed the benefits and limitations of the
      presacral retroperitoneal approach for L5-S1 interbody fusion. The purpose of
      this study was to determine the safety and effectiveness of the minimally
      invasive axial lumbar interbody approach (AxiaLIF) for L4-S1 fusion. METHODS: In
      this retrospective series, 52 patients from four clinical sites underwent L4-S1
      interbody fusion with the AxiaLIF two-level system with minimum 2-year clinical
      and radiographic follow-up (range: 24-51 months). Outcomes included back pain
      severity (on a 10-point scale), the Oswestry Disability Index (ODI), and Odom's
      criteria. Flexion and extension radiographs, as well as computed tomography
      scans, were evaluated to determine fusion status. Longitudinal outcomes were
      assessed with repeated measures analysis of variance. RESULTS: Mean subject age
      was 52 +/- 11 years and the male:female ratio was 1:1. Patients sustained no
      intraoperative bowel or vascular injury, deep infection, or neurologic
      complication. Median procedural blood loss was 220 cc and median length of
      hospital stay was 3 days. At 2-year follow-up, mean back pain had improved 56%,
      from 7.7 +/- 1.6 at baseline to 3.4 +/- 2.7 (P < 0.001). Back pain clinical
      success (ie, >=30% improvement from baseline) was achieved in 39 (75%) patients
      at 2 years. Mean ODI scores improved 42%, from 60% +/- 16% at baseline to 35% +/-
      27% at 2 years (P < 0.001). ODI clinical success (ie, >=30% improvement from
      baseline) was achieved in 26 (50%) patients. At final follow-up, 45 (87%)
      patients were rated as good or excellent, five as fair, and two as poor by Odom's
      criteria. Interbody fusion observed on imaging was achieved in 97 (93%) of 104
      treated interspaces. During follow-up, five patients underwent reoperation on the
      lumbar spine, including facet screw removal (two), laminectomy (two), and
      transforaminal lumbar interbody fusion (one). CONCLUSION: The AxiaLIF two-level
      device is a safe, effective treatment adjunct for patients with L4-S1 disc
      pathology resistant to conservative treatments.

PMID- 24092997
TI  - Advances in cortical modulation of pain.
AB  - Pain is an intricate phenomenon composed of not only sensory-discriminative
      aspects but also of emotional, cognitive, motivational, and affective components.
      There has been ample evidence for the existence of an extensive cortical network
      associated with pain processing over the last few decades. This network includes
      the anterior cingulate cortex, forebrain, insular cortex, ventrolateral orbital
      cortex, somatosensory cortex, occipital cortex, retrosplenial cortex, motor
      cortex, and prefrontal cortex. Diverse neurotransmitters participate in the
      cortical circuits associated with pain processing, including glutamate, gamma
      aminobutyric acid, dopamine, and opioids. This work examines recent rodent
      studies about cortical modulation of pain, mainly at a molecular level. 

PMID- 24092999
TI  - Exercise in a healthy heart program: a cohort study.
AB  - OBJECTIVE: To assess the effects of exercise on resting heart rate (RHR), weight,
      lipid profile, and blood pressure. We hypothesized that the participants who
      increased their physical activity would show improvement in their cardiovascular
      risk factors compared to those who did not. DESIGN: Retrospective chart review
      over the mean duration of 4.9 years of follow-up. SETTING: Healthy Heart Program
      Prevention Clinic at St. Paul's Hospital, Vancouver, British Columbia, Canada.
      PARTICIPANTS: We reviewed 300 charts of patients randomly selected from those who
      attended the Prevention Clinic between 1984 and 2009. 248 (82.7%) patients were
      referred for primary prevention and 52 (17.3%) for secondary prevention. PRIMARY
      AND SECONDARY OUTCOME MEASURES: Weight, RHR, lipid profile, and blood pressure
      were recorded at the initial and last visit. RESULTS: During a mean of 4.9 years
      of follow-up, 55% of participants improved their exercise. The mean decrease in
      the RHR for these patients (group 1) was 5.9 beats per minute (bpm) versus the
      mean increase of 0.3 bpm for the "no change" group (group 2) (P < 0.01). The mean
      net weight increase in group 1 was 0.06 kg/year versus 0.25 kg/year in group 2.
      Because of medications, all patients had a significant improvement in their lipid
      profiles. Furthermore, there was a statistically significant greater reduction in
      Framingham Risk Score (FRS) in group 1 versus group 2 (11.8% versus 15.1%, P <
      0.01). CONCLUSION: Participation in the program significantly reduces modifiable
      risk factors for cardiovascular disease. Improved exercise regimen results in
      lower RHR and greater reduction in FRS. However, even in a Prevention Program,
      despite strong advocacy of the importance of exercise, a significant percentage
      of participants does not improve their exercise habits.

PMID- 24093000
TI  - Atrial natriuretic Peptide single nucleotide polymorphisms in patients with
      nonfamilial structural atrial fibrillation.
AB  - BACKGROUND: Atrial natriuretic peptide (ANP) has antihypertrophic and
      antifibrotic properties that are relevant to AF substrates. The -G664C and rs5065
      ANP single nucleotide polymorphisms (SNP) have been described in association with
      clinical phenotypes, including hypertension and left ventricular hypertrophy. A
      recent study assessed the association of early AF and rs5065 SNPs in low-risk
      subjects. In a Caucasian population with moderate-to-high cardiovascular risk
      profile and structural AF, we conducted a case-control study to assess whether
      the ANP -G664C and rs5065 SNP associate with nonfamilial structural AF. METHODS:
      168 patients with nonfamilial structural AF and 168 age- and sex-matched controls
      were recruited. The rs5065 and -G664C ANP SNPs were genotyped. RESULTS: The study
      population had a moderate-to-high cardiovascular risk profile with 86% having
      hypertension, 23% diabetes, 26% previous myocardial infarction, and 23% left
      ventricular systolic dysfunction. Patients with AF had greater left atrial
      diameter (44 +/- 7 vs. 39 +/- 5 mm; P < 0.001) and higher plasma NTproANP levels
      (6240 +/- 5317 vs. 3649 +/- 2946 pmol/mL; P < 0.01). Odds ratios (ORs) for rs5065
      and -G664C gene variants were 1.1 (95% confidence interval [CI], 0.7-1.8; P =
      0.71) and 1.2 (95% CI, 0.3-3.2; P = 0.79), respectively, indicating no
      association with AF. There were no differences in baseline clinical
      characteristics among carriers and noncarriers of the -664C and rs5065 minor
      allele variants. CONCLUSIONS: We report lack of association between the rs5065
      and -G664C ANP gene SNPs and AF in a Caucasian population of patients with
      structural AF. Further studies will clarify whether these or other ANP gene
      variants affect the risk of different subphenotypes of AF driven by distinct
      pathophysiological mechanisms.

PMID- 24093001
TI  - Thrombotic thrombocytopenic purpura: three peripartum cases and diagnostic
      challenges.
AB  - Thrombotic thrombocytopenic purpura (TTP) is a medical emergency characterized by
      occlusive microangiopathy due to intravascular platelet aggregation. This event
      results in damage to the red blood cells (RBCs) known as microangiopathic
      hemolytic anemia (MAHA). Schistocytes are circulating fragments of damaged RBCs
      that have different morphological features including keratocytes, helmet cells,
      and spherocytes. It is critical to report even a small number of these abnormal
      RBCs in the peripheral blood and to be alert for the possible diagnosis of TTP,
      especially in unexplained anemia and thrombocytopenia. The application of pentad
      criteria in the diagnosis has been reviewed, and the challenges still remained on
      the hematologic evidence of this disorder. In the 3 cases discussed here, the red
      cell morphological diagnosis gave an impact on TTP diagnosis, but overdiagnosis
      might be encountered in obstetrical patients due to nonspecific diagnostic
      criteria. 

PMID- 24093002
TI  - Use of noninvasive gas exchange to track pulmonary vascular responses to exercise
      in heart failure.
AB  - We determined whether a non-invasive gas exchange based estimate of pulmonary
      vascular (PV) capacitance [PVCAP = stroke volume (SV) * pulmonary arterial
      pressure (Ppa)] (GXCAP) tracked the PV response to exercise in heart-failure (HF)
      patients. Pulmonary wedge pressure (Ppw), Ppa, PV resistance (PVR), and gas
      exchange were measured simultaneously during cycle exercise in 42 HF patients
      undergoing right-heart catheterization. During exercise, PETCO2 and VE/VCO2 were
      related to each other (r = -0.93, P < 0.01) and similarly related to mean Ppa
      (mPpa) (r = -0.39 and 0.36; P < 0.05); PETCO2 was subsequently used as a metric
      of mPpa. Oxygen pulse (O2 pulse) tracked the SV response to exercise (r = 0.91, P
      < 0.01). Thus, GXCAP was calculated as O2 pulse * PETCO2. During exercise,
      invasively determined PVCAP and non-invasive GXCAP were related (r = 0.86, P <
      0.01), and GXCAP correlated with mPpa and PVR (r = -0.46 and -0.54; P < 0.01). In
      conclusion, noninvasive gas exchange measures may represent a simple way to track
      the PV response to exercise in HF. 

PMID- 24093003
TI  - Are Faces Special to Infants? An Investigation of Configural and Featural
      Processing for the Upper and Lower Regions of Houses in 3- to 7-month-olds.
AB  - Three- to 7-month-olds were administered a house version of the Face Dimensions
      Test in which the featural and configural information of the upper and lower
      windows were systematically varied. The Dimensions Test has previously been used
      to study the processing of face features and their configurations by infants
      (Quinn & Tanaka, 2009). Just as was the case with faces, infants were shown to be
      sensitive to configural change in the upper and lower regions and to featural
      change in the upper region, but not to featural change in the lower region. The
      outcomes reflect either a face processing system that can generalize broadly to
      stimuli that are as different from faces as houses or a more general processing
      system with perceptual operations that can apply to both faces and houses.

PMID- 24093004
TI  - Optimized Structure and Vibrational Properties by Error Affected Potential Energy
      Surfaces.
AB  - The precise theoretical determination of the geometrical parameters of molecules
      at the minima of their potential energy surface and of the corresponding
      vibrational properties are of fundamental importance for the interpretation of
      vibrational spectroscopy experiments. Quantum Monte Carlo techniques are
      correlated electronic structure methods promising for large molecules, which are
      intrinsically affected by stochastic errors on both energy and force
      calculations, making the mentioned calculations more challenging with respect to
      other more traditional quantum chemistry tools. To circumvent this drawback in
      the present work, we formulate the general problem of evaluating the molecular
      equilibrium structures, the harmonic frequencies, and the anharmonic coefficients
      of an error affected potential energy surface. The proposed approach, based on a
      multidimensional fitting procedure, is illustrated together with a critical
      evaluation of systematic and statistical errors. We observe that the use of
      forces instead of energies in the fitting procedure reduces the statistical
      uncertainty of the vibrational parameters by 1 order of magnitude. Preliminary
      results based on variational Monte Carlo calculations on the water molecule
      demonstrate the possibility to evaluate geometrical parameters and harmonic and
      anharmonic coefficients at this level of theory with an affordable computational
      cost and a small stochastic uncertainty (<0.07% for geometries and <0.7% for
      vibrational properties).

PMID- 24093005
TI  - Characterization of tibetan medicine zuota by multiple techniques.
AB  - Zuota is regarded as the king of Tibetan medicine. However, due to the
      confidentiality of this precious medicine, the scientific characterization of
      Zuota is very scarce, which limits the pharmacology and biosafety studies of
      Zuota. Herein, we collected four different Zuota samples from Tibet, Qinghai,
      Gansu, and Sichuan and characterized them by multiple techniques. Our results
      showed that Zuota was mainly an inorganic mixture of HgS, sulfur, and graphite.
      Morphologically, Zuota samples were composed of nanoparticles, which further
      aggregated into microsized particles. Chemically, the majorities of Zuota were S
      and Hg (in the forms of HgS and pure sulfur). All samples contained pure sulfur
      with orthorhombic crystalline. Zuota from Qinghai province had different HgS
      crystalline, namely, hexagonal crystalline. The others were all face-centered
      cubic crystalline. Carbon in Zuota NPs was in the form of graphite. The
      implication to future studies of Zuota was discussed. 

PMID- 24093006
TI  - Encapsulating Elastically Stretchable Neural Interfaces: Yield, Resolution, and
      Recording/Stimulation of Neural Activity.
AB  - A high resolution elastically stretchable microelectrode array (SMEA) to
      interface with neural tissue is described. The SMEA consists of an elastomeric
      substrate, such as poly(dimethylsiloxane) (PDMS), elastically stretchable gold
      conductors, and an electrically insulating encapsulating layer in which contact
      holes are opened. We demonstrate the feasibility of producing contact holes with
      40 um * 40 um openings, show why the adhesion of the encapsulation layer to the
      underlying silicone substrate is weakened during contact hole fabrication, and
      provide remedies. These improvements result in greatly increased fabrication
      yield and reproducibility. An SMEA with 28 microelectrodes was fabricated. The
      contact holes (100 um * 100 um) in the encapsulation layer are only ~10% the size
      of the previous generation, allowing a larger number of microelectrodes per unit
      area, thus affording the capability to interface with a smaller neural population
      per electrode. This new SMEA is used to record spontaneous and evoked activity in
      organotypic hippocampal tissue slices at 0% strain before stretching, at 5 % and
      10 % equibiaxial strain, and again at 0% strain after relaxation. The noise of
      the recordings increases with increasing strain. The frequency of spontaneous
      neural activity also increases when the SMEA is stretched. Upon relaxation, the
      noise returns to pre-stretch levels, while the frequency of neural activity
      remains elevated. Stimulus-response curves at each strain level are measured. The
      SMEA shows excellent biocompatibility for at least two weeks.

PMID- 24093008
TI  - Corticospinal tract insult alters GABAergic circuitry in the mammalian spinal
      cord.
AB  - During perinatal development, corticospinal tract (CST) projections into the
      spinal cord help refine spinal circuitry. Although the normal developmental
      processes that are controlled by the arrival of corticospinal input are becoming
      clear, little is known about how perinatal cortical damage impacts specific
      aspects of spinal circuit development, particularly the inhibitory microcircuitry
      that regulates spinal reflex circuits. In this study, we sought to determine how
      ischemic cortical damage impacts the synaptic attributes of a well-characterized
      population of inhibitory, GABAergic interneurons, called GABApre neurons, which
      modulates the efficiency of proprioceptive sensory terminals in the sensorimotor
      reflex circuit. We found that putative GABApre interneurons receive CST input
      and, using an established mouse model of perinatal stroke, that cortical ischemic
      injury results in a reduction of CST density within the intermediate region of
      the spinal cord, where these interneurons reside. Importantly, CST alterations
      were restricted to the side contralateral to the injury. Within the synaptic
      terminals of the GABApre interneurons, we observed a dramatic upregulation of the
      65-isoform of the GABA synthetic enzyme glutamic acid decarboxylase (GAD65). In
      accordance with the CST density reduction, GAD65 was elevated on the side of the
      spinal cord contralateral to cortical injury. This effect was not seen for other
      GABApre synaptic markers or in animals that received sham surgery. Our data
      reveal a novel effect of perinatal stroke that involves severe deficits in the
      architecture of a descending spinal pathway, which in turn appear to promote
      molecular alterations in a specific spinal GABAergic circuit. 

PMID- 24093007
TI  - Ghrelin and ghrelin receptor modulation of psychostimulant action.
AB  - Ghrelin (GHR) is an orexigenic gut peptide that modulates multiple homeostatic
      functions including gastric emptying, anxiety, stress, memory, feeding, and
      reinforcement. GHR is known to bind and activate growth-hormone secretagogue
      receptors (termed GHR-Rs). Of interest to our laboratory has been the assessment
      of the impact of GHR modulation of the locomotor activation and
      reward/reinforcement properties of psychostimulants such as cocaine and nicotine.
      Systemic GHR infusions augment cocaine stimulated locomotion and conditioned
      place preference (CPP) in rats, as does food restriction (FR) which elevates
      plasma ghrelin levels. Ghrelin enhancement of psychostimulant function may occur
      owing to a direct action on mesolimbic dopamine function or may reflect an
      indirect action of ghrelin on glucocorticoid pathways. Genomic or pharmacological
      ablation of GHR-Rs attenuates the acute locomotor-enhancing effects of nicotine,
      cocaine, amphetamine and alcohol and blunts 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. Inactivation of ghrelin circuit function in rats by
      injection of a ghrelin receptor antagonist (e.g., JMV 2959) diminishes the
      development of nicotine-induced locomotor sensitization. These results suggest a
      key permissive role for GHR-R activity for the induction of locomotor
      sensitization to nicotine. Our finding that GHR-R null rats exhibit diminished
      patterns of responding for intracranial self-stimulation complements an emerging
      literature implicating central GHR circuits in drug reward/reinforcement.
      Finally, antagonism of GHR-Rs may represent a smoking cessation modality that not
      only blocks nicotine-induced reward but that also may limit weight gain after
      smoking cessation. 

PMID- 24093009
TI  - An error-related negativity potential investigation of response monitoring
      function in individuals with internet addiction disorder.
AB  - Internet addiction disorder (IAD) is an impulse disorder or at least related to
      impulse control disorder. Deficits in executive functioning, including response
      monitoring, have been proposed as a hallmark feature of impulse control
      disorders. The error-related negativity (ERN) reflects individual's ability to
      monitor behavior. Since IAD belongs to a compulsive-impulsive spectrum disorder,
      theoretically, it should present response monitoring functional deficit
      characteristics of some disorders, such as substance dependence, ADHD, or alcohol
      abuse, testing with an Erikson flanker task. Up to now, no studies on response
      monitoring functional deficit in IAD were reported. The purpose of the present
      study was to examine whether IAD displays response monitoring functional deficit
      characteristics in a modified Erikson flanker task. Twenty-three subjects were
      recruited as IAD group. Twenty-three matched age, gender, and education healthy
      persons were recruited as control group. All participants completed the modified
      Erikson flanker task while measured with event-related potentials. IAD group made
      more total error rates than did controls (p < 0.01); Reactive times for total
      error responses in IAD group were shorter than did controls (p < 0.01). The mean
      ERN amplitudes of total error response conditions at frontal electrode sites and
      at central electrode sites of IAD group were reduced compared with control group
      (all p < 0.01). These results revealed that IAD displays response monitoring
      functional deficit characteristics and shares ERN characteristics of compulsive
      impulsive spectrum disorder. 

PMID- 24093010
TI  - An fMRI study of affective perspective taking in individuals with psychopathy:
      imagining another in pain does not evoke empathy.
AB  - While it is well established that individuals with psychopathy have a marked
      deficit in affective arousal, emotional empathy, and caring for the well-being of
      others, the extent to which perspective taking can elicit an emotional response
      has not yet been studied despite its potential application in rehabilitation. In
      healthy individuals, affective perspective taking has proven to be an effective
      means to elicit empathy and concern for others. To examine neural responses in
      individuals who vary in psychopathy during affective perspective taking, 121
      incarcerated males, classified as high (n = 37; Hare psychopathy checklist
      revised, PCL-R >= 30), intermediate (n = 44; PCL-R between 21 and 29), and low (n
      = 40; PCL-R <= 20) psychopaths, were scanned while viewing stimuli depicting
      bodily injuries and adopting an imagine-self and an imagine-other perspective.
      During the imagine-self perspective, participants with high psychopathy showed a
      typical response within the network involved in empathy for pain, including the
      anterior insula (aINS), anterior midcingulate cortex (aMCC), supplementary motor
      area (SMA), inferior frontal gyrus (IFG), somatosensory cortex, and right
      amygdala. Conversely, during the imagine-other perspective, psychopaths exhibited
      an atypical pattern of brain activation and effective connectivity seeded in the
      anterior insula and amygdala with the orbitofrontal cortex (OFC) and ventromedial
      prefrontal cortex (vmPFC). The response in the amygdala and insula was inversely
      correlated with PCL-R Factor 1 (interpersonal/affective) during the imagine-other
      perspective. In high psychopaths, scores on PCL-R Factor 1 predicted the neural
      response in ventral striatum when imagining others in pain. These patterns of
      brain activation and effective connectivity associated with differential
      perspective-taking provide a better understanding of empathy dysfunction in
      psychopathy, and have the potential to inform intervention programs for this
      complex clinical problem. 

PMID- 24093011
TI  - Environmental enrichment may protect against hippocampal atrophy in the chronic
      stages of traumatic brain injury.
AB  - OBJECTIVE: To examine the relationship between environmental enrichment (EE) and
      hippocampal atrophy in the chronic stages of moderate to severe traumatic brain
      injury (TBI). DESIGN: Retrospective analysis of prospectively collected data;
      observational, within-subjects. PARTICIPANTS: Patients (N = 25) with moderate to
      severe TBI. MEASURES: Primary predictors: (1) An aggregate of self-report rating
      of EE (comprising hours of cognitive, physical, and social activities) at 5
      months post-injury; (2) pre-injury years of education as a proxy for pre-morbid
      EE (or cognitive reserve). PRIMARY OUTCOME: bilateral hippocampal volume change
      from 5 to 28 months post-injury. RESULTS: As predicted, self-reported EE was
      significantly negatively correlated with bilateral hippocampal atrophy (p <
      0.05), with greater EE associated with less atrophy from 5 to 28 months. Contrary
      to prediction, years of education (a proxy for cognitive reserve) was not
      significantly associated with atrophy. CONCLUSION: Post-injury EE may serve as a
      buffer against hippocampal atrophy in the chronic stages of moderate-severe TBI.
      Clinical application of EE should be considered for optimal maintenance of
      neurological functioning in the chronic stages of moderate-severe TBI.

PMID- 24093012
TI  - Making long-term memories in minutes: a spaced learning pattern from memory
      research in education.
AB  - Memory systems select from environmental stimuli those to encode permanently.
      Repeated stimuli separated by timed spaces without stimuli can initiate Long-Term
      Potentiation (LTP) and long-term memory (LTM) encoding. These processes occur in
      time scales of minutes, and have been demonstrated in many species. This study
      reports on using a specific timed pattern of three repeated stimuli separated by
      10 min spaces drawn from both behavioral and laboratory studies of LTP and LTM
      encoding. A technique was developed based on this pattern to test whether
      encoding complex information into LTM in students was possible using the pattern
      within a very short time scale. In an educational context, stimuli were periods
      of highly compressed instruction, and spaces were created through 10 min
      distractor activities. Spaced Learning in this form was used as the only means of
      instruction for a national curriculum Biology course, and led to very rapid LTM
      encoding as measured by the high-stakes test for the course. Remarkably, learning
      at a greatly increased speed and in a pattern that included deliberate
      distraction produced significantly higher scores than random answers (p <
      0.00001) and scores were not significantly different for experimental groups (one
      hour spaced learning) and control groups (four months teaching). Thus learning
      per hour of instruction, as measured by the test, was significantly higher for
      the spaced learning groups (p < 0.00001). In a third condition, spaced learning
      was used to replace the end of course review for one of two examinations. Results
      showed significantly higher outcomes for the course using spaced learning (p <
      0.0005). The implications of these findings and further areas for research are
      briefly considered. 

PMID- 24093013
TI  - Investment and repayment in a trust game after ventromedial prefrontal damage.
AB  - Although trust and reciprocity are ubiquitous in social exchange, their
      neurobiological substrate remains largely unknown. Here, we investigated the
      effect of damage to the ventromedial prefrontal cortex (vmPFC)-a brain region
      critical for valuing social information-on individuals' decisions in a trust game
      and in a risk game. In the trust game, one player, the investor, is endowed with
      a sum of money, which she can keep or invest. The amount she decides to invest is
      tripled and sent to the other player, the trustee, who then decides what fraction
      to return to the investor. In separate runs, ten patients with focal bilateral
      damage to the vmPFC and control participants made decision while playing in the
      role of either investor or trustee with different anonymous counterparts in each
      run. A risk game was also included in which the investor faced exactly the same
      decisions as in the trust game, but a random device (i.e., a computer), not
      another player, determined the final payoffs. Results showed that vmPFC patients'
      investments were not modulated by the type of opponent player (e.g., human vs.
      computer) present in the environment. Thus, vmPFC patients showed comparable risk
      taking preferences both in social (trust game) and nonsocial (risk game)
      contexts. In stark contrast, control participants were less willing to take risk
      and invest when they believed that they were interacting with people than a
      computer. Furthermore, when acted as trustee, vmPFC patients made lower back
      transfers toward investors, thereby showing less reciprocity behavior. Taken
      together, these results indicate that social valuation and emotion subserved by
      vmPFC have a critical role in trusting and reciprocity decisions. The present
      findings support the hypothesis that vmPFC damage may impair affective systems
      specifically designed for mediating social transaction with other individuals. 

PMID- 24093014
TI  - Investigating the role of visual and auditory search in reading and developmental
      dyslexia.
AB  - It has been suggested that auditory and visual sequential processing deficits
      contribute to phonological disorders in developmental dyslexia. As an alternative
      explanation to a phonological deficit as the proximal cause for reading
      disorders, the visual attention span hypothesis (VA Span) suggests that
      difficulties in processing visual elements simultaneously lead to dyslexia,
      regardless of the presence of a phonological disorder. In this study, we assessed
      whether deficits in processing simultaneously displayed visual or auditory
      elements is linked to dyslexia associated with a VA Span impairment. Sixteen
      children with developmental dyslexia and 16 age-matched skilled readers were
      assessed on visual and auditory search tasks. Participants were asked to detect a
      target presented simultaneously with 3, 9, or 15 distracters. In the visual
      modality, target detection was slower in the dyslexic children than in the
      control group on a "serial" search condition only: the intercepts (but not the
      slopes) of the search functions were higher in the dyslexic group than in the
      control group. In the auditory modality, although no group difference was
      observed, search performance was influenced by the number of distracters in the
      control group only. Within the dyslexic group, not only poor visual search (high
      reaction times and intercepts) but also low auditory search performance (d')
      strongly correlated with poor irregular word reading accuracy. Moreover, both
      visual and auditory search performance was associated with the VA Span abilities
      of dyslexic participants but not with their phonological skills. The present data
      suggests that some visual mechanisms engaged in "serial" search contribute to
      reading and orthographic knowledge via VA Span skills regardless of phonological
      skills. The present results further open the question of the role of auditory
      simultaneous processing in reading as well as its link with VA Span skills. 

PMID- 24093015
TI  - The anatomy of choice: active inference and agency.
AB  - This paper considers agency in the setting of embodied or active inference. In
      brief, we associate a sense of agency with prior beliefs about action and ask
      what sorts of beliefs underlie optimal behavior. In particular, we consider prior
      beliefs that action minimizes the Kullback-Leibler (KL) divergence between
      desired states and attainable states in the future. This allows one to formulate
      bounded rationality as approximate Bayesian inference that optimizes a free
      energy bound on model evidence. We show that constructs like expected utility,
      exploration bonuses, softmax choice rules and optimism bias emerge as natural
      consequences of this formulation. Previous accounts of active inference have
      focused on predictive coding and Bayesian filtering schemes for minimizing free
      energy. Here, we consider variational Bayes as an alternative scheme that
      provides formal constraints on the computational anatomy of inference and action
      constraints that are remarkably consistent with neuroanatomy. Furthermore, this
      scheme contextualizes optimal decision theory and economic (utilitarian)
      formulations as pure inference problems. For example, expected utility theory
      emerges as a special case of free energy minimization, where the sensitivity or
      inverse temperature (of softmax functions and quantal response equilibria) has a
      unique and Bayes-optimal solution-that minimizes free energy. This sensitivity
      corresponds to the precision of beliefs about behavior, such that attainable
      goals are afforded a higher precision or confidence. In turn, this means that
      optimal behavior entails a representation of confidence about outcomes that are
      under an agent's control. 

PMID- 24093016
TI  - Multisite functional connectivity MRI classification of autism: ABIDE results.
AB  - BACKGROUND: Systematic differences in functional connectivity MRI metrics have
      been consistently observed in autism, with predominantly decreased cortico
      cortical connectivity. Previous attempts at single subject classification in high
      functioning autism using whole brain point-to-point functional connectivity have
      yielded about 80% accurate classification of autism vs. control subjects across a
      wide age range. We attempted to replicate the method and results using the Autism
      Brain Imaging Data Exchange (ABIDE) including resting state fMRI data obtained
      from 964 subjects and 16 separate international sites. METHODS: For each of 964
      subjects, we obtained pairwise functional connectivity measurements from a
      lattice of 7266 regions of interest covering the gray matter (26.4 million
      "connections") after preprocessing that included motion and slice timing
      correction, coregistration to an anatomic image, normalization to standard space,
      and voxelwise removal by regression of motion parameters, soft tissue, CSF, and
      white matter signals. Connections were grouped into multiple bins, and a leave
      one-out classifier was evaluated on connections comprising each set of bins. Age,
      age-squared, gender, handedness, and site were included as covariates for the
      classifier. RESULTS: Classification accuracy significantly outperformed chance
      but was much lower for multisite prediction than for previous single site
      results. As high as 60% accuracy was obtained for whole brain classification,
      with the best accuracy from connections involving regions of the default mode
      network, parahippocampaland fusiform gyri, insula, Wernicke Area, and
      intraparietal sulcus. The classifier score was related to symptom severity,
      social function, daily living skills, and verbal IQ. Classification accuracy was
      significantly higher for sites with longer BOLD imaging times. CONCLUSIONS:
      Multisite functional connectivity classification of autism outperformed chance
      using a simple leave-one-out classifier, but exhibited poorer accuracy than for
      single site results. Attempts to use multisite classifiers will likely require
      improved classification algorithms, longer BOLD imaging times, and standardized
      acquisition parameters for possible future clinical utility.

PMID- 24093017
TI  - Side effect of acting on the world: acquisition of action-outcome statistic
      relation alters visual interpretation of action outcome.
AB  - Humans can acquire the statistical features of the external world and employ them
      to control behaviors. Some external events occur in harmony with an agent's
      action, and thus, humans should also be able to acquire the statistical features
      between an action and its external outcome. We report that the acquired action
      outcome statistical features alter the visual appearance of the action outcome.
      Pressing either of two assigned keys triggered visual motion whose direction was
      statistically biased either upward or downward, and observers judged the stimulus
      motion direction. Points of subjective equality (PSE) for judging motion
      direction were shifted repulsively from the mean of the distribution associated
      with each key. Our Bayesian model accounted for the PSE shifts, indicating the
      optimal acquisition of the action-effect statistical relation. The PSE shifts
      were moderately attenuated when the action-outcome contingency was reduced. The
      Bayesian model again accounted for the attenuated PSE shifts. On the other hand,
      when the action-outcome contiguity was reduced, the PSE shifts were greatly
      attenuated, and however, the Bayesian model could not accounted for the shifts.
      The results indicate that visual appearance can be modified by prediction based
      on the optimal acquisition of action-effect causal relation. 

PMID- 24093018
TI  - Sirtuins in neurodegenerative diseases: an update on potential mechanisms.
AB  - Silent information regulator 2 proteins (sirtuins or SIRTs) are a group of
      deacetylases (or deacylases) whose activities are dependent on and regulated by
      nicotinamide adenine dinucleotide (NAD(+)). Compelling evidence supports that
      sirtuins play major roles in many aspects of physiology, especially in pathways
      related to aging - the predominant and unifying risk factor for neurodegenerative
      diseases. In this review, we highlight the molecular mechanisms underlying the
      protective effects of sirtuins in neurodegenerative diseases, focusing on protein
      homeostasis, neural plasticity, mitochondrial function, and sustained chronic
      inflammation. We will also examine the potential and challenges of targeting
      sirtuin pathways to block these pathogenic pathways. 

PMID- 24093020
TI  - Pleasure and addiction.
AB  - What is the role and value of pleasure in addiction? Foddy and Savulescu (1) have
      claimed that substance use is just pleasure-oriented behavior. They describe
      addiction as "strong appetites toward pleasure" and argue that addicts suffer in
      significant part because of strong social and moral disapproval of lives
      dominated by pleasure seeking. But such lives, they claim, can be autonomous and
      rational. The view they offer is largely in line with the choice model and
      opposed to a disease model of addiction. Foddy and Savulescu are sceptical of
      self-reports that emphasize the ill effects of addiction such as loss of family
      and possessions, or that claim an absence of pleasure after tolerance sets in.
      Such reports they think are shaped by social stigma which makes available a
      limited set of socially approved addiction narratives. We will not question the
      claim that a life devoted to pleasure can be autonomously chosen. Nor do we
      question the claim that the social stigma attached to the use of certain drugs
      increases the harm suffered by the user. However our interviews with addicts (as
      philosophers rather than health professionals or peers) reveal a genuinely
      ambivalent and complex relationship between addiction, value, and pleasure. Our
      subjects did not shy away from discussing pleasure and its role in use. But
      though they usually valued the pleasurable properties of substances, and this
      played that did not mean that they valued an addictive life. Our interviews
      distinguished changing attitudes towards drug related pleasures across the course
      of substance use, including diminishing pleasure from use over time and
      increasing resentment at the effects of substance use on other valued activities.
      In this paper we consider the implications of what drug users say about pleasure
      and value over the course of addiction for models of addiction. 

PMID- 24093019
TI  - The role of cholesterol metabolism and cholesterol transport in carcinogenesis: a
      review of scientific findings, relevant to future cancer therapeutics.
AB  - While the unique metabolic activities of malignant tissues as potential targets
      for cancer therapeutics has been the subject of several recent reviews, the role
      of cholesterol metabolism in this context is yet to be fully explored.
      Cholesterol is an essential component of mammalian cell membranes as well as a
      precursor of bile acids and steroid hormones. The hypothesis that cancer cells
      need excess cholesterol and intermediates of the cholesterol biosynthesis pathway
      to maintain a high level of proliferation is well accepted, however the
      mechanisms by which malignant cells and tissues reprogram cholesterol synthesis,
      uptake and efflux are yet to be fully elucidated as potential therapeutic
      targets. High and low density plasma lipoproteins are the likely major suppliers
      of cholesterol to cancer cells and tumors, potentially via receptor mediated
      mechanisms. This review is primarily focused on the role(s) of lipoproteins in
      carcinogenesis, and their future roles as drug delivery vehicles for targeted
      cancer chemotherapy. 

PMID- 24093021
TI  - Photobacterium damselae subsp. damselae, a bacterium pathogenic for marine
      animals and humans.
AB  - Photobacterium damselae subsp. damselae (formerly Vibrio damsela) is a pathogen
      of a variety of marine animals including fish, crustaceans, molluscs, and
      cetaceans. In humans, it can cause opportunistic infections that may evolve into
      necrotizing fasciitis with fatal outcome. Although the genetic basis of virulence
      in this bacterium is not completely elucidated, recent findings demonstrate that
      the phospholipase-D Dly (damselysin) and the pore-forming toxins HlyApl and
      HlyAch play a main role in virulence for homeotherms and poikilotherms. The
      acquisition of the virulence plasmid pPHDD1 that encodes Dly and HlyApl has
      likely constituted a main driving force in the evolution of a highly hemolytic
      lineage within the subspecies. Interestingly, strains that naturally lack pPHDD1
      show a strong pathogenic potential for a variety of fish species, indicating the
      existence of yet uncharacterized virulence factors. Future and deep analysis of
      the complete genome sequence of Photobacterium damselae subsp. damselae will
      surely provide a clearer picture of the virulence factors employed by this
      bacterium to cause disease in such a varied range of hosts. 

PMID- 24093023
TI  - Heterochronic genes in plant evolution and development.
AB  - Evolution of morphology includes evolutionary shifts of developmental processes
      in space or in time. Heterochronic evolution is defined as a temporal shift. The
      concept of heterochrony has been very rewarding to investigators of both animal
      and plant developmental evolution, because it has strong explanatory power when
      trying to understand morphological diversity. While for animals, extensive
      literature on heterochrony developed along with the field of evolution of
      development, in plants the concept has been applied less often and is less
      elaborately developed. Yet novel genetic findings highlight heterochrony as a
      developmental and evolutionary process in plants. Similar to what has been found
      for the worm Caenorhabditis, a heterochronic gene pathway controlling
      developmental timing has been elucidated in flowering plants. Two antagonistic
      microRNA's miR156 and miR172 target two gene families of transcription factors,
      SQUAMOSA PROMOTOR BINDING PROTEIN-LIKE and APETALA2-like, respectively. Here, we
      propose that this finding now allows the molecular investigation of cases of
      heterochronic evolution in plants. We illustrate this point by examining microRNA
      expression patterns in the Antirrhinum majus incomposita and choripetala
      heterochronic mutants. Some of the more beautiful putative cases of heterochronic
      evolution can be found outside flowering plants, but little is known about the
      extent of conservation of this flowering plant pathway in other land plants. We
      show that the expression of an APETALA2-like gene decreases with age in a fern
      species. This contributes to the idea that ferns share some heterochronic gene
      functions with flowering plants. 

PMID- 24093024
TI  - PedWiz: a web-based tool for pedigree informatics.
AB  - A novel web-based tool PedWiz that pipelines the informatics process for pedigree
      data is introduced. PedWiz is designed to assist researchers in the analysis of
      pedigree data. It provides a convenient tool for pedigree informatics:
      descriptive statistics, relative pairs, genetic similarity coefficients, the
      variance-covariance matrix for three estimated coefficients of allele identical
      by-descent sharing as well as mean allele sharing, a plot of the pedigree
      structures, and a visualization of the identity coefficients. With a renewed
      interest in linkage and other family based methods, PedWiz will be a valuable
      tool for the analysis of family data. 

PMID- 24093026
TI  - On becoming a new pharmacist / Devenir pharmacien.

PMID- 24093025
TI  - Xanthogranulomatous appendicitis in a child: report of a case and review of the
      literature.
AB  - Xanthogranulomatous inflammation is a well-described inflammatory process, which
      may involve any organ but is most frequently encountered in the gall bladder and
      the kidney. There are rare reports of xanthogranulomatous appendicitis (XA) in
      the adult population, but only one brief mention of such a diagnosis in a child.
      In this report, we describe the case of an 11-year-old boy who presented with
      clinical signs and symptoms of acute appendicitis necessitating appendectomy.
      Upon microscopic examination, the appendix showed the typical features of XA. To
      the best of our knowledge, this is the first well-described case XA in a
      noninterval appendix in a child. We also reviewed the limited medical literature
      on the subject. 

PMID- 24093022
TI  - Evolution and Conservation of Plant NLR Functions.
AB  - In plants and animals, nucleotide-binding domain and leucine-rich repeats (NLR)
      containing proteins play pivotal roles in innate immunity. Despite their similar
      biological functions and protein architecture, comparative genome-wide analyses
      of NLRs and genes encoding NLR-like proteins suggest that plant and animal NLRs
      have independently arisen in evolution. Furthermore, the demonstration of
      interfamily transfer of plant NLR functions from their original species to
      phylogenetically distant species implies evolutionary conservation of the
      underlying immune principle across plant taxonomy. In this review we discuss
      plant NLR evolution and summarize recent insights into plant NLR-signaling
      mechanisms, which might constitute evolutionarily conserved NLR-mediated immune
      mechanisms. 

PMID- 24093027
TI  - Reducing polypharmacy in the elderly: Cases to help you "rock the boat".

PMID- 24093028
TI  - Clinical services.

PMID- 24093029
TI  - Addressing the authorization of orphan drugs will not fix reimbursement problems:
      The elephant is still in the room.

PMID- 24093030
TI  - Nova Scotia pharmacies preparing to administer flu vaccines with approval of new
      authority.

PMID- 24093031
TI  - Manitoba pharmacists scheduled to complete vote by late July on regulations for
      2006 Pharmaceutical Act.

PMID- 24093032
TI  - Panel reviewing cancer drug error presents report to Ontario government.

PMID- 24093033
TI  - Neil MacKinnon named Dean of College of Pharmacy at University of Cincinnati.

PMID- 24093034
TI  - Celebrating innovation and entrepreneurship at the University of Waterloo.

PMID- 24093035
TI  - Public health watch.

PMID- 24093036
TI  - Cardiovascular risk factor modification among high-risk patients: Do pharmacists
      play a role?

PMID- 24093037
TI  - Reducing pill burden and helping with medication awareness to improve adherence.

PMID- 24093038
TI  - [Not Available].

PMID- 24093039
TI  - Evaluation of a medication order writing standards policy in a regional health
      authority.
AB  - BACKGROUND: The Winnipeg Regional Health Authority (WRHA) implemented a
      medication order writing standards (MOWS) policy (including banned abbreviations)
      to improve patient safety. Widespread educational campaigns and direct prescriber
      feedback were implemented. METHODS: We audited orders within the WRHA from 2005
      to 2009 and surveyed all WRHA staff in 2011 about the policy and suggestions for
      improving education and compliance. RESULTS: Overall, orders containing banned
      abbreviations, acronyms or symbols numbered 2261/8565 (26.4%) preimplementation.
      After WRHA-wide didactic education, the proportion declined to 1358/5461 (24.9%)
      (p = 0.043) and then, with targeted prescriber feedback, to 1186/6198 (19.1%) (p
      < 0.0001). A survey of 723 employees showed frequent violations of the MOWS,
      despite widespread knowledge of the policy. Respondents supported ongoing efforts
      to enforce the policy within the WRHA. Nonprescribers were significantly more
      likely than prescribers to agree with statements regarding enhancing compliance
      by defining prescriber/transcriber responsibilities and placing sanctions on
      noncompliant prescribers. DISCUSSION: Education, raising general awareness and
      targeted feedback to prescribers alone are insufficient to ensure compliance with
      MOWS policies. WRHA staff supported ongoing communication, improved tools such as
      compliant preprinted orders and reporting and feedback about medication
      incidents. A surprising number of respondents supported placing sanctions on
      noncompliant prescribers. CONCLUSION: Serial audits and targeted interventions
      such as direct prescriber feedback improve prescription quality in inpatient
      hospital settings. Education plus direct prescriber feedback had a greater impact
      than education alone on improving compliance with a MOWS policy. Future efforts
      at the WRHA to improve compliance will require an expanded focus on incentives,
      resources and development of action plans that involve all affected staff, not
      just prescribers. Plans include continued advertising, MOWS summaries in all
      charts, all-staff education, reminders and exploration of sustainable
      interventions for targeted feedback for prescribers.

PMID- 24093041
TI  - First impressions of the world of pharmacy.

PMID- 24093040
TI  - Collaborative Cardiovascular Risk Reduction in Primary Care II (CCARP II):
      Implementation of a systematic case-finding process for patients with
      uncontrolled risk factors.
AB  - BACKGROUND: Previous pharmacist interventions to reduce cardiovascular (CV) risk
      have been limited by low patient enrolment. The primary aim of this study was to
      implement a collaborative pharmacist intervention that used a systematic case
      finding procedure to identify and manage patients with uncontrolled CV risk
      factors. METHODS: This was an uncontrolled, program implementation study. We
      implemented a collaborative pharmacist intervention in a primary care clinic. All
      adults presenting for an appointment with a participating physician were
      systematically screened and assessed for CV risk factor control by the
      pharmacist. Recommendations for risk factor management were communicated on a
      standardized form, and the level of pharmacist follow-up was determined on a case
      by-case basis. We recorded the proportion of adults exhibiting a moderate to high
      Framingham risk score and at least 1 uncontrolled risk factor. In addition, we
      assessed before-after changes in CV risk factors. RESULTS: Of the 566 patients
      who were screened prior to visiting a participating physician, 186 (32.9%)
      exhibited moderate or high CV risk along with at least 1 uncontrolled risk
      factor. Physicians requested pharmacist follow-up for 60.8% (113/186) of these
      patients. Of the patients receiving the pharmacist intervention, 65.5% (74/113)
      were at least 50% closer to 1 or more of their risk factor targets by the end of
      the study period. Significant risk factor improvements from baseline were also
      observed. DISCUSSION: Through implementation of a systematic case-finding
      approach that was carried out by the pharmacist on behalf of the clinic team, a
      large number of patients with uncontrolled risk factors were identified, assessed
      and managed with a collaborative intervention. CONCLUSION: Systematic case
      finding appears to be an important part of a successful intervention to identify
      and manage individuals exhibiting uncontrolled CV risk factors in a primary care
      setting.

PMID- 24093042
TI  - Working together to strengthen the voice of pharmacy.

PMID- 24093043
TI  - 2013 Abstracts and Posters: Canadian Pharmacists Association Conference,
      Charlottetown, PEI.

PMID- 24093044
TI  - Possible implication of Fc gamma receptor-mediated trogocytosis in susceptibility
      to systemic autoimmune disease.
AB  - Leukocytes can "gnaw away" the plasma membrane of other cells. This phenomenon,
      called trogocytosis, occurs subsequent to cell-to-cell adhesion. Currently, two
      mechanisms of trogocytosis, adhesion molecule-mediated trogocytosis and Fc gamma
      receptor-(Fc gamma R-) mediated trogocytosis, have been identified. In our
      earlier study, we established an in vitro model of Fc gamma R-mediated
      trogocytosis, namely, CD8 translocation model from T cells to neutrophils. By
      using this model, we demonstrated that the molecules transferred to neutrophils
      via Fc gamma R-mediated trogocytosis were taken into the cytoplasm immediately.
      This result suggests that the chance of molecules transferred via Fc gamma R
      mediated trogocytosis to play a role on the cell surface could be time-limited.
      Thus, we consider the physiological role of Fc gamma R-mediated trogocytosis as a
      means to remove antibodies (Abs) that bind with self-molecules rather than to
      extract molecules from other cells. This concept means that Fc gamma R-mediated
      trogocytosis can be a defense mechanism to Ab-mediated autoimmune response.
      Moreover, the activity of Fc gamma R-mediated trogocytosis was revealed to be
      parallel to the endocytotic activity of neutrophils, which was critically related
      to the susceptibility to systemic autoimmune diseases. The collective findings
      suggest that Fc gamma R-mediated trogocytosis could physiologically play a role
      in removal of Abs bound to self-antigens and prevent autoimmune diseases. 

PMID- 24093045
TI  - Host defense against common early life-threatening infections.

PMID- 24093046
TI  - Open Randomized Clinical Trial on JWSJZ Decoction for the Treatment of ALS
      Patients.
AB  - Objective. To investigate the efficacy and safety of the traditional Chinese
      medicine Jiawei Sijunzi (JWSJZ) decoction for the treatment of patients with
      amyotrophic lateral sclerosis (ALS). Methods. Forty-eight patients with ALS were
      divided into a JWSJZ group (n = 24) and a control group (n = 24) using a
      randomized number method. Together with the basic treatment for ALS, JWSJZ
      decoction was added to the treatment regimen of patients in the JWSJZ group or
      Riluzole was administered to the control group for 6 months. Neurologists
      evaluated the treated and control patients using the ALS functional rating scale
      (ALSFRS) before, 3 and 6 months after starting the additional treatments.
      Results. The ALSFRS scores in both groups were lower 3 and 6 months after
      treatment than before. There was a significant difference at 6 months after
      treatment between the subgroups of patients with ALS whose limbs were the initial
      site of attack. No serious adverse effects were observed in the JWSJZ group.
      Conclusion. JWSJZ decoction may be a safe treatment for ALS, and may have delayed
      the development of ALS, especially in the subgroup of patients in whom the limbs
      were attacked first when compared with Riluzole treatment. 

PMID- 24093047
TI  - Herbal Medicines: Malaysian Women's Knowledge and Practice.
AB  - This is a cross-sectional, descriptive study among Malay women admitted in the
      antenatal and postnatal ward to determine the prevalence and use of herbal
      medicines during pregnancy and elemental analysis in the most popular herbs. A
      total of 460 women were surveyed. Herbal medicine use during pregnancy was 34.3%,
      while 73% utilized herbal medicines during labor, because of a belief that it may
      shorten and ease labor. The most commonly used herbal medicines in pregnancy were
      Anastatica hierochuntica L. (60.1%) followed by coconut oil (35.4%). The majority
      of women (89.2%) used only one type of herbal medicines and took one
      capsule/glass (38%) per day. Herbal medicines use by pregnant women is largely
      unsupervised (81%), with most women getting information from their parents
      (60.7%) and buying the products directly from traditional midwives (32.2%) and
      77% agreed upon its efficacy and safety. From the 460 respondents, 89.8% women
      were in the low end of the herbs knowledge. There was a significant difference
      found between knowledge score and income (P < 0.05). Microdiffraction analysis
      revealed significant presence of carbon, oxygen, silica, calcium, magnesium,
      aluminium, potassium, zinc, and iron that were found in Anastatica hierochuntica
      L. and proved to have good benefits for pregnancy. 

PMID- 24093048
TI  - Filovirus replication and transcription.
AB  - The highly pathogenic filoviruses, Marburg and Ebola virus, belong to the
      nonsegmented negative-sense RNA viruses of the order Mononegavirales. The mode of
      replication and transcription is similar for these viruses. On one hand, the
      negative-sense RNA genome serves as a template for replication, to generate
      progeny genomes, and, on the other hand, for transcription, to produce mRNAs.
      Despite the similarities in the replication/transcription strategy, filoviruses
      have evolved structural and functional properties that are unique among the
      nonsegmented negative-sense RNA viruses. Moreover, there are also striking
      differences in the replication and transcription mechanisms of Marburg and Ebola
      virus. This includes nucleocapsid formation, the structure of the genomic
      replication promoter, the protein requirement for transcription and the use of
      mRNA editing. In this article, the current knowledge of the replication and
      transcription strategy of Marburg and Ebola virus is reviewed, with focus on the
      observed differences.

PMID- 24093050
TI  - Carotid Artery Stenosis Associated with Increased Mortality in Patients who
      Underwent Coronary Artery Bypass Grafting: A Single Center Experience.
AB  - BACKGROUND: Vascular disease resulting from arteriosclerosis is a severe
      worldwide health risk. Early diagnosis and intervention is important to control
      adverse cerebral and cardiovascular events. The aim of this study was to assess
      the potential predictors of mortality in patients submitted to coronary bypass
      surgery. METHODS: Cohort study included asymptomatic cerebrovascular disease
      patients scheduled for coronary artery bypass grafting admitted to the cardiology
      reference center. All patients were submitted to carotid artery ultrasound
      assessment prior to surgery and were followed up during the entire in-hospital
      postoperative period. Carotid artery stenosis was considered clinically
      significant when cross sectional area >=50%. Significance was set at p <0.05.
      Logistic regression was used to identify independent predictors of mortality.
      RESULTS: Of 455 patients with a mean age of 62.2 years 65.6% were males. The
      prevalence of carotid artery stenosis was 18.7%. It was absent in 3.6% of the
      patients, below 50% in 77.8%, between 50 and 69% in 11.6%, and between 70 and 99%
      in 6.9%. The carotid artery was occluded in 0.2% of the sample. An overall
      mortality of 12%, affecting 35 men (P=0.001) with stenosis >=50%. After logistic
      regression analysis, carotid artery stenosis >=50% was confirmed as being an
      independent predictor of mortality (P=0.005). CONCLUSION: In this series carotid
      artery stenosis showed a high prevalence in the sample assessed and was an
      independent predictor of mortality.

PMID- 24093049
TI  - NDE1 and NDEL1: twin neurodevelopmental proteins with similar 'nature' but
      different 'nurture'.
AB  - Nuclear distribution element 1 (NDE1, also known as NudE) and NDE-like 1 (NDEL1,
      also known as Nudel) are paralogous proteins essential for mitosis and
      neurodevelopment that have been implicated in psychiatric and neurodevelopmental
      disorders. The two proteins possess high sequence similarity and have been shown
      to physically interact with one another. Numerous lines of experimental evidence
      in vivo and in cell culture have demonstrated that these proteins share common
      functions, although instances of differing functions between the two have
      recently emerged. We review the key aspects of NDE1 and NDEL1 in terms of recent
      advances in structure elucidation and cellular function, with an emphasis on
      their differing mechanisms of post-translational modification. Based on a review
      of the literature and bioinformatics assessment, we advance the concept that the
      twin proteins NDE1 and NDEL1, while sharing a similar 'nature' in terms of their
      structure and basic functions, appear to be different in their 'nurture', the
      manner in which they are regulated both in terms of expression and of post
      translational modification within the cell. These differences are likely to be of
      significant importance in understanding the specific roles of NDE1 and NDEL1 in
      neurodevelopment and disease.

PMID- 24093051
TI  - Pre-operative assessment and post-operative care in elective shoulder surgery.
AB  - Pre-operative assessment is required prior to the majority of elective surgical
      procedures, primarily to ensure that the patient is fit to undergo surgery,
      whilst identifying issues that may need to be dealt with by the surgical or
      anaesthetic teams. The post-operative management of elective surgical patients
      begins during the peri-operative period and involves several health
      professionals. Appropriate monitoring and repeated clinical assessments are
      required in order for the signs of surgical complications to be recognised
      swiftly and adequately. This article examines the literature regarding pre
      operative assessment in elective orthopaedic surgery and shoulder surgery, whilst
      also reviewing the essentials of peri- and post-operative care. The need to
      recognise common post-operative complications early and promptly is also
      evaluated, along with discussing thromboprophylaxis and post-operative analgesia
      following shoulder surgery. 

PMID- 24093053
TI  - Editorial: management of neck pain.

PMID- 24093052
TI  - Hyaluronic Acid (HA) Viscosupplementation on Synovial Fluid Inflammation in Knee
      Osteoarthritis: A Pilot Study.
AB  - OBJECTIVE: This study examined the changes in synovial fluid levels of cytokines,
      oxidative stress and viscosity six months after intraarticular hyaluronic acid
      (HA) treatment in adults and elderly adults with knee osteoarthritis (OA).
      DESIGN: This was a prospective, repeated-measures study design in which patients
      with knee OA were administered 1% sodium hyaluronate. Patients (N=28) were
      stratified by age (adults, 50-64 years and elderly adults, >=65 years).
      Ambulatory knee pain values and self-reported physical activity were collected at
      baseline and month six. MATERIALS AND METHODS: Knee synovial fluid aspirates were
      collected at baseline and at six months. Fluid samples were analyzed for pro
      inflammatory cytokines (interleukins 1beta, 6,8,12, tumor necrosis factor-alpha,
      monocyte chemotactic protein), anti-inflammatory cytokines (interleukins 4, 10
      13), oxidative stress (4-hydroxynonenal) and viscosity at two different
      physiological shear speeds 2.5Hz and 5Hz. RESULTS: HA improved ambulatory knee
      pain in adults and elderly groups by month six, but adults reported less knee
      pain-related interference with participation in exercise than elderly adults. A
      greater reduction in TNF-alpha occurred in adults compared to elderly adults (
      95.8% +/- 7.1% vs 19.2% +/- 83.8%, respectively; p=.044). Fluid tended to improve
      at both shear speeds in adults compared to the elderly adults. The reduction in
      pain severity correlated with the change in IL-1beta levels by month six (r= 
      .566; p=.044). CONCLUSION: Reduction of knee pain might be due to improvements in
      synovial fluid viscosity and inflammation. Cartilage preservation may be
      dependent on how cytokine, oxidative stress profiles and viscosity change over
      time.

PMID- 24093055
TI  - The roles of inflammatory cytokines in the pathogenesis of ossification of
      ligamentum flavum.
AB  - Ossification of Ligamentum Flavum (OLF) is associated with serious neurologic
      symptoms including thoracic myelopathy and spinal stenosis. The pathogenesis of
      thoracic OLF is mainly due to the localized mechanical stress on the ligament
      induced enchondral ossification. However, despite numerous epidemiological and
      basic science studies, the mechanism of this process remains unclear. Studies
      have suggested that inflammatory cytokines, such as IL-6, TNF-alpha, seem to play
      a crucial role in OLF. In this review, we summarise the mechanistic information
      on the roles of inflammation cytokines in OLF and discuss about several
      therapeutic methods for OLF. Further studies on the role of cytokines in OLF
      should provide important insights into the designation of therapeutic strategies
      in preventing human spinal stenosis caused by OLF. 

PMID- 24093054
TI  - CD133: to be or not to be, is this the real question?
AB  - CD133 (promini-1) is a member of the transmembrane glycoprotein family, was
      initially described as a specific marker to select human hematopoietic progenitor
      cells. Then, it was recognised as important marker to identify and isolate the
      specific cell subpopulation termed "cancer stem cells". Many studies showed that
      CD133(+) cells have stemness properties such as self-renewal, differentiation
      ability, high proliferation and they are able also to form tumours in xenografts.
      Moreover it has been demonstrated that CD133(+) cells more resistant to radiation
      and standard chemotherapy than CD133(-) cells. Although this, others
      investigations demonstrated that also CD133(-) cells can show the same
      characteristics of those positive for CD133(+). Hence, some inconsistencies among
      published data on CD133 function can be ascribed to different causes questioning
      the main role as specific marker of cancer stem cells. In fact, many authors
      indicate that CD133 is expressed both in differentiated and undifferentiated
      cells, and CD133(-) cancer cells can also initiate tumours. Indeed, it is still a
      matter of debate whether CD133(+) cells truly represent the ultimate tumourigenic
      population. However, the belief that CD133 may act as a universal marker of CSCs
      has been met with a high degree of controversy in the research community. In this
      review there is an attempt to highlight: i) the role and function of CD133, with
      an overview on the current stage of knowledge about this molecule, ii) the
      difficulty often encountered in its identification iii) the utility of CD133
      expression as a prognostic marker. 

PMID- 24093056
TI  - Non-chemical and non-contact cell-to-cell communication: a short review.
AB  - Cell-to-cell communication is the basis of coordinated cellular activity and thus
      fundamental for the functioning of biological systems. In a recently published
      research article by Chaban et al. (Am. J. Transl. Res., 5(1), 69-79), the authors
      report on interesting new experimental findings supporting a neuro-hormonal
      independent, non-diffusible cell-to-cell signaling. Our paper aims to (i) discuss
      some critical notions used by the authors to describe their findings, and (ii)
      briefly review related experimental work performed so far but not discussed in
      the original work of Chaban et al. In our opinion, the research on principles of
      non-chemical and non-contact cell-to-cell communication has the potential to
      offer new fundamental insights into biological processes. With this paper, we
      want to encourage future research on this topic by discussing critical issues and
      giving an overview of the current state of research. 

PMID- 24093057
TI  - Effects of a superoxide dismutase mimetic on biomarkers of lung angiogenesis and
      alveolarization during hyperoxia with intermittent hypoxia.
AB  - Extremely premature neonates requiring oxygen therapy develop an accumulation of
      reactive oxygen species (ROS), impaired alveolarization and dysmorphic pulmonary
      vasculature. Regulators of ROS (i.e. antioxidants), alveolarization (i.e. matrix
      metalloproteinases - MMPs) and microvascular maturation (i.e. vascular
      endothelial growth factor - VEGF) are altered in bronchopulmonary dysplasia
      (BPD). We tested the hypothesis that early treatment with MnTBAP, a superoxide
      dismutase mimetic and superoxide anion and peroxynitrite scavenger, alters lung
      biomarkers of angiogenesis and alveolarization during hyperoxia with intermittent
      hypoxia (IH) in neonatal rats. Neonatal rats were exposed to 50% O2 with brief IH
      episodes (12% O2) from P0 to P14, or to room air (RA). On P0, P1 & P2, the pups
      received a daily IP injection of 1, 5, or 10 mg/kg MnTBAP, or saline. At P14, the
      pups were either euthanized, or allowed to recover in RA until P21. RA
      littermates were similarly treated. Lung VEGF, sVEGFR-1, MMP-2, MMP-9 and TIMP-1
      were determined. Low-dose MnTBAP (1 mg/kg) prevented the increase in lung VEGF
      induced by intermittent hypoxia noted in the control group. This dose was also
      effective for decreasing MMP-9 and MMP-9/TIMP-1 ratio suggesting an anti
      inflammatory effect for MnTBAP. IH decreased MMP-2 with no ameliorating effect by
      MnTBAP. Our data demonstrate that brief, repeated intermittent hypoxia during
      hyperoxia can alter biomarkers responsible for normal microvascular and alveolar
      development. In addition to prevention of hypoxic events, the use of antioxidants
      needs to be explored as a possible therapeutic intervention in neonates at risk
      for the development of oxidative lung injury. 

PMID- 24093059
TI  - A novel piperazine derivative potently induces caspase-dependent apoptosis of
      cancer cells via inhibition of multiple cancer signaling pathways.
AB  - Despite rapid progress in anticancer drug development and improvement in clinical
      outcomes, the survival rate for many types of cancer is still unacceptably low.
      Therefore, it is crucial to discover novel anticancer drugs to both prevent and
      treat the disease. In recent years, the advent of combinatorial chemistry allows
      the design and parallel synthesis of millions of small compounds that have drug
      like properties. In vitro high throughput screening of such compound libraries
      has allowed the identification of many new drug candidates that may be further
      evaluated for their efficacy and mechanism of action. The overall objective of
      this study was to identify small molecule compounds as candidates for anti-cancer
      drug development. We first used cell proliferation and cytotoxicity assays to
      identify compounds exhibiting anti-cancer activity in vitro in a leukemia cell
      line (K562). Six top compounds selected from the initial screening of a library
      of 2,560 compounds were further evaluated in multiple cancer cell lines to rank
      the drug candidates. The top candidate was further investigated to elucidate the
      molecular mechanism underlying its anticancer activity. Our studies suggest that
      this piperazine derivative effectively (GI50 = 0.06-0.16 MUM) inhibits cancer
      cell proliferation and induces caspase-dependent apoptosis via inhibiting
      multiple cancer signaling pathways including the PI3K/AKT, the Src family kinases
      and the BCR-ABL pathways. 

PMID- 24093058
TI  - Distinct subcellular patterns of neprilysin protein and activity in the brains of
      Alzheimer's disease patients, transgenic mice and cultured human neuronal cells.
AB  - We investigated the subcellular distribution of NEP protein and activity in
      brains of human individuals with no cognitive impairment (NCI), mild cognitive
      impairment (MCI) and AD dementia, as well as double transgenic mice and human
      neuronal cell line treated with Abeta and 4-hydroxy-2-nonenal (HNE). Total
      cortical neuronal-related NEP was significantly increased in MCI compared to NCI
      brains. NeuN was decreased in both MCI and AD, consistent with neuronal loss
      occurring in MCI and AD. Negative relationship between NEP protein and NeuN in
      MCI brains, and positive correlation between NEP and pan-cadherin in NCI and MCI
      brains, suggesting the increased NEP expression in NCI and MCI might be due to
      membrane associated NEP in non-neuronal cells. In subcellular extracts, NEP
      protein decreased in cytoplasmic fractions in MCI and AD, but increased in
      membrane fractions, with a significant increase in the membrane/cytoplasmic ratio
      of NEP protein in AD brains. By contrast, NEP activity was decreased in AD.
      Similar results were observed in AD-mimic transgenic mice. Studies of SH-SY5Y
      neuroblastoma showed an up-regulation of NEP protein in the cytoplasmic
      compartment induced by HNE and Abeta; however, NEP activity decreased in
      cytoplasmic fractions. Activity of NEP in membrane fractions increased at 48
      hours and then significantly decreased after treatment with HNE and Abeta. The
      cytoplasmic/membrane ratio of NEP protein increased at 24 hours and then
      decreased in both HNE and Abeta treated cells. Both HNE and Abeta up-regulate NEP
      expression, but NEP enzyme activity did not show the same increase, possibly
      indicating immature cytoplasmic NEP is less active than membrane associated NEP.
      These observations indicate that modulation of NEP protein levels and its
      subcellular location influence the net proteolytic activity and this complex
      association might participate in deficiency of Abeta degradation that is
      associated with amyloid deposition in AD. 

PMID- 24093060
TI  - Mycoplasma hyorhinis markedly degrades beta-amyloid peptides in vitro and ex
      vivo: a novel biological approach for treating Alzheimer's disease?
AB  - Accumulation of amyloid-beta (Abeta) peptides (predominantly Abeta40, 42) and
      their aggregation into plaques in the brain are thought to be the one of the
      major causes of Alzheimer's disease (AD). Originally discovered in our Chinese
      hamster ovary (CHO) cell line stably expressing human wild-type amyloid precursor
      protein (APP) (CHO/APPwt) cultures devoid of Abeta production, we found that
      Mycoplasma selectively degrades soluble Abeta in a time and dose (colony forming
      unit) dependent manner. Moreover, we fully characterized the Mycoplasma species
      as Mycoplasma hyorhinis (M. hyorhinis) by genetic and colony morphological
      analyses by light microscopy. Most interestingly, we attenuated the pathogenicity
      of M. hyorhinis by gamma irradiation (3.5 Gy), and found that its ability to
      degrade Abeta was retained. On the other hand, heated and sonicated M. hyorhinis
      failed to retain this ability to degrade Abeta, suggesting that this degradation
      requires viable cells and likely a biologically active signaling pathway. In
      addition, we found that M. hyorhinis can degrade Abeta produced in AD model mice
      (PSAPP mice) ex vivo. Finally, we found that irradiated (non-pathogenic) M.
      hyorhinis also can degrade Abeta produced in PSAPP mice in vivo. These studies
      suggest that irradiated (non-pathogenic) M. hyorhinis can be a novel and
      alternative biological strategy for AD treatment. 

PMID- 24093061
TI  - Laparoscopic Roux-en-Y gastric bypass in super obese Gottingen minipigs.
AB  - BACKGROUND: The specific mechanisms behind weight loss and comorbidity
      improvements in obese patients after Roux-en-Y gastric bypass (RYGBP) are still
      poorly understood. The aim of this study was to establish and evaluate the
      feasibility of a long-term survival RYGBP model in super obese Gottingen minipigs
      in order to improve the translational potential relative to current animal
      models. METHODS: Eleven Gottingen minipigs with diet-induced obesity underwent
      laparoscopic RYGBP and were followed up to 9 months after surgery. Intra- and
      post-operative complications, body weight (BW), food intake and necropsy data
      were recorded. RESULTS: Five minipigs survived without complications to the end
      of the study. Four minipigs developed surgical related complications and were
      euthanized while two minipigs died due to central venous catheter related
      complications. BW and food intake is reported for the six minipigs surviving
      longer than 4.5 months post-surgery. Weight loss and reduced food intake was seen
      in all minipigs. After 2-3 months of weight loss, weight regain was evident in
      all but two minipigs which seemed to continue losing weight. Necropsy revealed
      some variation in the length of the alimentary, biliary and common limb between
      minipigs. CONCLUSION: The use of obese Gottingen minipigs as a translational
      RYGBP model is feasible and has potential for the study of RYGBP-related changes
      in gut function, type-2 diabetes and appetite regulation. Still, the surgical
      procedure is technically highly demanding in obese Gottingen minipigs and the
      peri-operative animal care and follow up requires close monitoring.

PMID- 24093062
TI  - Multivariable discriminant analysis for the differential diagnosis of microcytic
      anemia.
AB  - Introduction. Iron deficiency anemia and thalassemia are the most common causes
      of microcytic anemia. Powerful statistical computer programming enables sensitive
      discriminant analyses to aid in the diagnosis. We aimed at investigating the
      performance of the multiple discriminant analysis (MDA) to the differential
      diagnosis of microcytic anemia. Methods. The training group was composed of 200
      beta -thalassemia carriers, 65 alpha -thalassemia carriers, 170 iron deficiency
      anemia (IDA), and 45 mixed cases of thalassemia and acute phase response or iron
      deficiency. A set of potential predictor parameters that could detect differences
      among groups were selected: Red Blood Cells (RBC), hemoglobin (Hb), mean cell
      volume (MCV), mean cell hemoglobin (MCH), and RBC distribution width (RDW). The
      functions obtained with MDA analysis were applied to a set of 628 consecutive
      patients with microcytic anemia. Results. For classifying patients into two
      groups (genetic anemia and acquired anemia), only one function was needed; 87.9%
      beta -thalassemia carriers, and 83.3% alpha -thalassemia carriers, and 72.1% in
      the mixed group were correctly classified. Conclusion. Linear discriminant
      functions based on hemogram data can aid in differentiating between IDA and
      thalassemia, so samples can be efficiently selected for further analysis to
      confirm the presence of genetic anemia. 

PMID- 24093063
TI  - Physical functioning, perceived disability, and depressive symptoms in adults
      with arthritis.
AB  - This study investigated how physical functioning and perceived disability are
      related to depressive symptoms in adults with arthritis (n = 401). Participants
      self-reported depressive symptoms and disability. Objective measures of physical
      functioning included the 30-second chair stand test, 6-minute walk test, gait
      speed, balance, grip strength, and the seated reach test. Separate quantile
      regression models tested associations between each functional measure and
      depressive symptoms, controlling for age, gender, race, BMI, self-reported health
      status, and arthritis medication use. The association between perceived
      disability and depressive symptoms was also tested. Participants averaged 56.3 +/
      10.7 years; 85.8% were women; 64.3% were white. Lower distance in the 6-minute
      walk test, fewer chair stands, slower gait speed, and greater perceived
      disability were associated with greater depressive symptoms in unadjusted models
      (Ps < 0.05). Fewer chair stands and greater perceived disability were associated
      with more depressive symptoms in adjusted models (Ps < 0.05). Balance, grip
      strength, and seated reach were not related to depressive symptoms. The
      perception of being disabled was more strongly associated with depressive
      symptoms than reduced physical functioning. To reduce the risk of depression in
      arthritic populations, it may be critical to not only address physical symptoms
      but also to emphasize coping skills and arthritis self-efficacy. 

PMID- 24093064
TI  - Gestational diabetes mellitus: screening and outcomes in southern italian
      pregnant women.
AB  - Recent Italian guidelines exclude women <35 years old, without risk factors for
      gestational diabetes mellitus (GDM), from screening for GDM. To determine the
      effectiveness of these measures with respect to the International Association of
      the Diabetes and Pregnancy Study Groups (IADPSG) criteria, we evaluated 2,448
      pregnant women retrospectively enrolled in Calabria, southern Italy. GDM was
      diagnosed following the IADPSG 2010 criteria. Among 538 women <35 years old,
      without risk factors, who would have not been tested according to the Italian
      guidelines, we diagnosed GDM in 171 (31.8%) pregnants (7.0% of total pregnants).
      Diagnosis was made at baseline (55.6%), 1 hour (39.8%), or 2 hours (4.7%) during
      OGTT. Despite of appropriate treatment, GDM represented a risk factor for
      cesarean section, polyhydramnios, increased birth weight, admission to neonatal
      intensive care units, and large for gestational age. These outcomes were similar
      to those observed in GDM women at high risk for GDM. In conclusion, Italian
      recommendations failed to identify 7.0% of women with GDM, when compared to
      IADPSG criteria. The risk for adverse hyperglycaemic-related outcomes is similar
      in low-risk and high-risk pregnants with GDM. To limit costs of GDM screening,
      our data suggest to restrict OGTT to two steps (baseline and 1 hour). 

PMID- 24093065
TI  - Transient femoral nerve palsy complicating "blind" transversus abdominis plane
      block.
AB  - We present two cases of patients who reported quadriceps femoris weakness and
      hypoesthesia over the anterior thigh after an inguinal hernia repair under
      transversus abdominis plane (TAP) block. Transient femoral nerve palsy is the
      result of local anesthetic incorrectly injected between transversus abdominis
      muscle and transversalis fascia and pooling around the femoral nerve. Although it
      is a minor and self-limiting complication, it requires overnight hospital stay
      and observation of the patients. Performing the block under ultrasound guidance
      and injecting the least volume of local anesthetic required are ways of
      minimizing its incidence. 

PMID- 24093066
TI  - Granulocytic Sarcoma of Parotid Gland in a 4-Year-Old Child with Subleukemic AML:
      A Diagnostic Challenge!
AB  - A 4-year-old male child presented to our outpatient department with large
      swelling in the parotid region. Routine investigations were all within normal
      limits, and evaluation of complete blood count was normal except for anaemia.
      Excisional biopsy as a therapeutic diagnosis was done. Microscopic examination
      showed monomorphic population of discohesive, hyperchromatic small round cells
      having high N : C ratio, coarse chromatin, conspicuous nucleoli, and sometimes
      angulated nuclei lying in sheets. Immunohistochemistry was done to rule out
      possible differential diagnosis. Fine needle aspiration from the swelling showed
      predominant population of blast cells. Myeloperoxidase and PBO were strongly
      positive, and diagnosis of granulocytic sarcoma was confirmed. 

PMID- 24093067
TI  - Hypertension associated with coarctation of the aorta revisited: case-based
      update from experience of three children.
AB  - Coarctation of the aorta (CoA) can present with different clinical pictures
      depending on the severity of the narrowness in the coarcted aortic segment in an
      age range between newborn and adolescence. Sometimes, it can cause intracranial
      hemorrhage or infarction when diagnosis and treatment are delayed. The aim of
      this report is taking attention to CoA as a cause of systemic hypertension and is
      also emphasizing the differences of diagnostic approach for hypertension in
      children from adults. Two cases of hypertensive cerebral hemorrhage and one case
      of hypertensive cerebellar infarction associated with CoA are reported. These
      cases help us to pay attention to the possibility of CoA in adolescents with
      hypertensive stroke. We want to emphasize the importance of physical examination
      for evaluation of hypertension and to impress the diagnostic approach for
      secondary hypertension in children. 

PMID- 24093068
TI  - Catatonia, neuroleptic malignant syndrome, and cotard syndrome in a 22-year-old
      woman: a case report.
AB  - The following case study describes a 22-year-old woman with depression and
      symptoms of psychosis who developed neuroleptic malignant syndrome after using
      Risperidone, thus requiring life support equipment and Bromocriptine, later
      recovering after seven days. From a psychiatric and neurological point of view,
      however, the persistence of catatonic syndrome and Cotard syndrome delusions was
      observed, based on assertions such as "I do not have a heart," "my heart is not
      beating," "I can not breathe," "I am breaking apart," "I have no head" (ideas of
      negation) and statements about the patient being responsible for the "death of
      the whole world" (ideas of enormity). Brain NMR revealed leukoencephalopathy,
      interpreted as scar lesions caused by perinatal neurological damage, after
      discarding other pathologies. The patient responded well to electroconvulsive
      therapy after 11 sessions. Organic vulnerability to these syndromes, as well as
      their coexistence and clinical differentiation is discussed in the light of the
      data observed. 

PMID- 24093069
TI  - Sleeptalking! Sleepwalking! Side effects of montelukast.
AB  - A 16-year-old Caucasian female presented to the pulmonary clinic for a followup
      on her asthma. Due to the worsening of allergy-related symptoms, therapy with
      montelukast 10 mg daily was started and resulted in good relief of the patient's
      symptoms. In the nights following initiating therapy with montelukast, the
      patient's mother reported daily parasomnias in the form of sleeptalking and
      sleepwalking. Montelukast was discontinued, and that resulted in absence of the
      parasomnias. In a second attempt montelukast was reinstituted to control the
      patient's symptoms. Parasomnias were immediately reported after resuming therapy.
      Montelukast was then discontinued indefinitely. Our patient has never had any
      history of parasomnias, and since the discontinuation of montelukast, parasomnias
      were never reported again. Parasomnias in the form of sleeptalking or
      sleepwalking were not previously reported as adverse effects of montelukast.
      Alternative modalities to treat allergy-related symptoms in patients, who develop
      parasomnias while receiving montelukast, should be explored. 

PMID- 24093070
TI  - Two-step laparoscopic surgery for a patient with synchronous double cancer of the
      colon and stomach accompanied by severe chronic obstructive pulmonary disease.
AB  - Laparoscopic treatment strategies for synchronous intra-abdominal malignancies
      have not yet been standardized. We report a successful case of two-step
      laparoscopic surgery for synchronous double cancer of the colon and stomach
      accompanied by severe chronic obstructive pulmonary disease (COPD). A 66-year-old
      man with COPD was diagnosed as having advanced colon cancer and early gastric
      cancer. On admission, he could not go upstairs (Grade III according to the Hugh
      Jones classification) and his forced expiratory volume in 1 second was 600 mL
      (35.9%). The patient initially underwent laparoscopy-assisted sigmoidectomy with
      D3 lymphadenectomy, followed by laparoscopy-assisted distal gastrectomy with D1
      lymphadenectomy 68 days later. The patient's each postoperative course was
      uneventful with no pulmonary complications, and the patient was discharged 9 and
      11 days after the first and second operations, respectively. The present case
      demonstrates that two-step laparoscopic surgery may be a safe and feasible
      surgical procedure for high-risk patients with synchronous intra-abdominal
      malignancies. 

PMID- 24093071
TI  - Salmonella appendicitis in renal transplantation.
AB  - While appendicitis remains one of the commonest surgical diseases, there are
      relatively few reports following renal transplantation. A 33-year-old man was
      admitted with diarrhea, fever, and epigastric pain 7 years following a cadaveric
      renal transplant. CT scanning confirmed a diagnosis of appendicitis which was
      removed within 24 hours of admission. Histology and blood cultures following
      surgery confirmed Salmonella type b appendicitis. Patient was safely discharged
      home 5 days following hospital admission. 

PMID- 24093072
TI  - Successful Kidney Transplantation for End-Stage Renal Disease in Marfan's
      Syndrome.
AB  - Marfan's syndrome is a systemic disorder of the connective tissue caused by
      mutations in the extracellular matrix protein fibrillin-1, with aortic dissection
      and aneurysm being its most life-threatening manifestations. Kidney
      transplantation for end-stage renal disease (ESRD) in patients with Marfan's
      syndrome has not been reported in the literature, and the rate of the incidence
      of dissection or aneurysm in the iliac artery is unknown. Here, we present a
      patient with Marfan's syndrome with ESRD due to severe renal ischemia caused by
      massive bleeding from thoracoabdominal aortic dissection leading to transplant
      surgery of a living kidney procured from the patient's mother. After kidney
      transplantation, the renal function normalized without vascular complications,
      and stable graft function along with negative results for both microhematuria and
      proteinuria continued for two years. Also, vascular complication such as aneurysm
      or dissection of the iliac artery was not observed using ultrasonography during
      the follow-up period. ESRD patients with Marfan's syndrome might be suitable for
      kidney transplantation, but long-term and careful observations are needed. 

PMID- 24093073
TI  - Differences in Serum Levels of Magnesium, Phosphate, and Albumin for HAART
      Experienced and HAART-Naive Female Patients Attending Parirenyatwa Opportunistic
      Infections Clinic in Harare, Zimbabwe.
AB  - Antiretroviral therapy inhibits HIV replication, maintains health, and preserves
      life. However, both antiretroviral therapy and HIV infection have been reported
      to have short- and long-term effects on bone metabolism. A cross-sectional study
      was performed to compare serum bone profiles in HIV positive patients on highly
      active antiretroviral therapy and compare them to therapy-naive patients. Serum
      levels of calcium, magnesium, phosphate, and albumin were measured in 40 female
      participants on highly active antiretroviral therapy, recruited sequentially from
      Parirenyatwa Opportunistic Infections Clinic, Harare, Zimbabwe. The 40 women were
      matched for age with 40 antiretroviral therapy-naive women. Magnesium, phosphate,
      and albumin levels were significantly higher in the therapy-naive than in therapy
      experienced patients. There was no statistically significant difference in
      calcium levels of the two groups of women. Evidence from this study suggests that
      highly active antiretroviral therapy lowers levels of magnesium, phosphate, and
      albumin but has no effect on levels of serum calcium. 

PMID- 24093074
TI  - Salvage of an infected periprosthetic failed fracture fixation in a nonagenarian.
AB  - Infected nonunions resulting in segmental bone loss are a devastating
      complication for patients and a difficult problem for surgeons. Adequate soft
      tissue coverage, return of mobility, fracture stability, and long-term freedom
      from infection are all important goals of treatment. Although there are numerous
      published studies that provide some treatment guidelines, there are patients who
      require unique and individualized solutions. In this report, we present a case in
      which an antibiotic-impregnated cement spacer was used as a component of the
      definitive treatment in a geriatric patient with segmental bone loss of the femur
      secondary to severe infection as a salvage technique to avoid amputation. 

PMID- 24093075
TI  - Preoperative thyroid dysfunction predicts 30-day postoperative complications in
      elderly patients with hip fracture.
AB  - OBJECTIVES: To investigate the relationship between thyroid function and short
      term outcomes in elderly patients undergoing surgery for hip fracture. METHODS:
      Patients aged >60 years admitted from July 2009 to June 2010 who underwent
      surgical fixation of low-energy hip fracture, excluding those with pathological
      or periprosthetic fracture, were enrolled in a retrospective observational cohort
      study. Patients were classified as having biochemically overt or subclinical
      hyperthyroidism or hypothyroidism, normal thyroid function, or nonclassifiable
      state based on preoperative thyroid-stimulating hormone and free thyroxine
      values. Outcome data were collected from hospital records. Biochemical thyroid
      dysfunction was not systematically treated. Outcomes measured were length of stay
      (LOS), 30-day postoperative complications, readmissions, and mortality. RESULTS:
      A total of 254 patients were analyzed; 64 (25.2%) were male and mean age was 77.8
      years. There were 128 (50.4%) patients with euthyroid, 68 (26.8%)
      nonclassifiable, 13 (5.1%) overtly hyperthyroid, 20 (7.9%) subclinically
      hyperthyroid, 4 (1.6%) overtly hypothyroid, and 21 (8.3%) subclinically
      hypothyroid. The 30-day postoperative complication rate was 38% (96 patients).
      The most common complication was urinary tract infection (12.6%), followed by
      cardiac events (8.3%) and delirium (5.5%). Patients with overt hyperthyroidism
      had an increased risk of complications in multivariate analysis (odds ratio 3.75,
      95% confidence interval 1.10-12.84). Complications in this group were similar to
      those in the overall cohort. Thyroid function did not predict LOS, readmissions,
      or mortality. CONCLUSION: Older patients frequently develop complications
      following surgery for hip fractures. This risk appears to be increased by
      preoperative biochemically overt hyperthyroidism. Further study is warranted to
      confirm this finding and to determine whether preoperative treatment improves
      outcomes.

PMID- 24093076
TI  - Salvaging the pullout strength of stripped screws in osteoporotic bone.
AB  - Our goal was to determine whether the pullout strength of stripped screw holes in
      osteoporotic bone could be increased with readily available materials from the
      operating room. We inserted 3.5-mm stainless steel nonlocking self-tapping
      cortical screws bicortically into 5 osteoporotic humeri. Each screw was first
      stripped by rotating it 1 full turn past maximum torque. In the control group,
      the screw was pulled out using an MTS machine (858; MTS Inc, Eden Prairie,
      Minnesota). In the treatment groups, the screw was removed, the hole was
      augmented with 1 of the 3 materials (stainless steel wire, polysorb suture, or
      polyethylene terephthalate glycol plastic sheet), and the screws were replaced
      and then pulled out. The effect of material on pullout strength was checked for
      significance (P < .05) using a general linearized latent and mixed model
      (Stata10; StataCorp, College Station, Texas). The mean (95% confidence interval)
      pullout strength for the unaugmented hole was 138 N (range 88-189), whereas the
      holes augmented with plastic, suture, or wire had mean pullout strengths of 255 N
      (range 177-333), 228 N (range 149-308), and 396 N (range 244-548), respectively.
      Although wire augmentation resulted in pullout strength that was significantly
      greater than that of the unaugmented screw, it was still below that of the intact
      construct. 

PMID- 24093077
TI  - The value of laboratory tests in diagnosing secondary osteoporosis at a fracture
      and osteoporosis outpatient clinic.
AB  - BACKGROUND: As more and more patients meeting the criteria for osteoporosis are
      referred to a fracture and osteoporosis outpatient clinic (FO clinic), the
      laboratory costs to screen for secondary osteoporosis also increases. This study
      was conducted to determine the value of screening on underlying diseases at an FO
      clinic by obtaining a standard set of laboratory tests. METHODS: We included all
      541 patients >=50 years with a fracture referred to our FO clinic, during the
      period January 2005 to January 2007. The bone mineral density (BMD) was measured
      by dual energy x-ray absorptiometry and expressed as a T score. A standard set of
      laboratory tests was obtained to screen on underlying diseases. RESULTS:
      Laboratory results were as often abnormal in patients with a normal BMD compared
      to patients with a low BMD. Underlying diseases were infrequently diagnosed.
      However, the prevalence of secondary osteoporosis in men was quite high, up to
      18.2%. The costs to diagnose 1 patient with an underlying disease did vary
      between ?92 and ?972 depending on the group of patients described. CONCLUSION:
      Screening all patients, referred to an FO clinic, for underlying diseases by
      obtaining a standard set of laboratory tests is probably not useful since
      laboratory tests are as often abnormal in patients with a normal BMD compared to
      patients with a low BMD. Moreover, the prevalence of secondary osteoporosis is
      low, while laboratory costs are substantial.

PMID- 24093078
TI  - Unchanging incidence of hip fracture in southeastern norway.
AB  - PURPOSE: The aim of this study was to ascertain trends in the incidence of hip
      fracture in southeastern Norway by comparing the hip fracture incidence for the
      years 2008 to 2010 to that of a study from 1998 to 2003 in the same area.
      METHODS: We determined the number of hip fractures for the geographical area of
      Ostfold county, and the age- and gender-specific incidence per 100 000, with 95%
      confidence intervals, was calculated. Use of bisphosphonates was determined by
      extracting data from public databases. RESULTS: The hip fracture incidence for
      men aged 50 to 74 and older than 75 years was 120 (100-141) and 1305 (1237-1372)
      in the latest time period, 1998-2003, whereas the incidence for the previous
      period, 2008-2010, was 124 (103-146) for men aged 50 to 75 and 1333 (1189-1476)
      for men older than 75 years. For women of 50 to 74 years, the incidence was 184
      (158-209), and for women older than 75 years, it was 2523 (2428-2618). In the
      first time period, the corresponding incidence was 228 (200-257) for women aged
      50 to 74 and 2330 (2189-2471) for women older than 75 years. As the 95%
      confidence intervals overlap in all the comparisons, it indicates the the
      incidence did not significantly differ between the time periods. Bisphosphonate
      use did not exceed 2% in any age group for men. For women, the highest rate of
      bisphosphonate use was 12.6% in the 85- to 89-year groups. CONCLUSION: We cannot
      confirm reports of decreasing incidence of hip fracture.

PMID- 24093079
TI  - Manuscript submission guidelines.

PMID- 24093080
TI  - Treatment of Alzheimer's Disease: Current Management and Experimental
      Therapeutics.
AB  - Alzheimer's disease (AD) is a major cause of morbidity in the elderly. AD affects
      aver 5 million persons in the United States, but because it increases in
      incidence in the elderly, and the "graying" population, AD is projected to
      increase in prevalence by many-fold over the coming decades. AD causes
      progressive mental impairment, resulting in the inability of persons to care for
      themselves. As a consequence, AD results in enormous costs to society due to both
      lost productivity, and required care. Thus, improved management and treatment is
      essential. In this review we will briefly review current understanding of the
      disease, including roles of beta-amyloid and tau proteins. We will then discuss
      current therapies in use, including the evidence for treatments with supplements,
      established drugs, and investigational therapeutic strategies, recently completed
      and ongoing.

PMID- 24093082
TI  - Therapies for human prion diseases.
AB  - The pathological foundation of human prion diseases is a result of the conversion
      of the physiological form of prion protein (PrP(c)) to the pathological protease
      resistance form PrP(res). Most patients with prion disease have unknown reasons
      for this conversion and the subsequent development of a devastating
      neurodegenerative disorder. The conversion of PrP(c) to PrP(res), with resultant
      propagation and accumulation results in neuronal death and amyloidogenesis.
      However, with increasing understanding of neurodegenerative processes it appears
      that protein-misfolding and subsequent propagation of these rouge proteins, is a
      generic phenomenon shared with diseases caused by tau, alpha-synucleins and beta
      amyloid proteins. Consequently, effective anti-prion agents may have wider
      implications. A number of therapeutic approaches include polyanionic, polycyclic
      drugs such as pentosan polysulfate (PPS), which prevent the conversion of PrP(c)
      to PrP(res) and might also sequester and down-regulate PrP(res). Polyanionic
      compounds might also help to clear PrP(res). Treatments aimed at the laminin
      receptor, which is an important accessory molecule in the conversion of PrP(c) to
      PrP(res) - neuroprotection, immunotherapy, siRNA and antisense approaches have
      provided some experimental promise. 

PMID- 24093083
TI  - Subjects harboring presenilin familial Alzheimer's disease mutations exhibit
      diverse white matter biochemistry alterations.
AB  - Alzheimer's disease (AD) dementia impacts all facets of higher order cognitive
      function and is characterized by the presence of distinctive pathological lesions
      in the gray matter (GM). The profound alterations in GM structure and function
      have fostered the view that AD impacts are primarily a consequence of GM damage.
      However, the white matter (WM) represents about 50% of the cerebrum and this area
      of the brain is substantially atrophied and profoundly abnormal in both sporadic
      AD (SAD) and familial AD (FAD). We examined the WM biochemistry by ELISA and
      Western blot analyses of key proteins in 10 FAD cases harboring mutations in the
      presenilin genes PSEN1 and PSEN2 as well as in 4 non-demented control (NDC)
      individuals and 4 subjects with SAD. The molecules examined were direct
      substrates of PSEN1 such as Notch-1 and amyloid precursor protein (APP). In
      addition, apolipoproteins, axonal transport molecules, cytoskeletal and
      structural proteins, neurotrophic factors and synaptic proteins were examined.
      PSEN-FAD subjects had, on average, higher amounts of WM amyloid-beta (Abeta)
      peptides compared to SAD, which may play a role in the devastating dysfunction of
      the brain. However, the PSEN-FAD mutations we examined did not produce uniform
      increases in the relative proportions of Abeta42 and exhibited substantial
      variability in total Abeta levels. These observations suggest that
      neurodegeneration and dementia do not depend solely on enhanced Abeta42 levels.
      Our data revealed additional complexities in PSEN-FAD individuals. Some direct
      substrates of gamma-secretase, such as Notch, N-cadherin, Erb-B4 and APP,
      deviated substantially from the NDC group baseline for some, but not all,
      mutation types. Proteins that were not direct gamma-secretase substrates, but
      play key structural and functional roles in the WM, likewise exhibited varied
      concentrations in the distinct PSEN mutation backgrounds. Detailing the diverse
      biochemical pathology spectrum of PSEN mutations may offer valuable insights into
      dementia progression and the design of effective therapeutic interventions for
      both SAD and FAD. 

PMID- 24093084
TI  - The time course of action of two neuroprotectants, dietary saffron and
      photobiomodulation, assessed in the rat retina.
AB  - BACKGROUND: Dietary saffron and photobiomodulation (low-level infrared radiation,
      PBM) are emerging as therapeutically promising protectants for neurodegenerative
      conditions, such as the retinal dystrophies. In animal models, saffron and PBM,
      given in limited daily doses, protect retina and brain from toxin- or light
      induced stress. This study addresses the rate at which saffron and PBM, given in
      daily doses, induce neuroprotection, using a light damage model of photoreceptor
      degeneration in Sprague Dawley (SD) rats. RESULTS: Rats were raised in dim cyclic
      (12 h 5 lux, 12 h dark) illumination, treated with saffron or PBM for 2-10 d, and
      then exposed to bright damaging light (1,000 lux for 24 h). After 1 week
      survival, the retina was assessed for photoreceptor death (using the TUNEL
      reaction), for surviving photoreceptor damage (thickness of the outer nuclear
      layer) and for the expression of a stress-related protein GFAP, using
      immunohistochemistry. Preconditioning the retina with saffron or PBM reduced
      photoreceptor death, preserved the population of surviving photoreceptors and
      reduced the upregulation of GFAP in Muller cells. At the daily dose of saffron
      used (1 mg/kg), protection was detectable at 2 d, increasing to 10 d. At the
      daily dose of PBM used (5 J/cm(2) at 670 nm) protection was detectable at 5 d,
      increasing to 7-10 d. CONCLUSIONS: The results provide time parameters for
      exploration of the mechanisms and durability of the protection provided by
      saffron and PBM.

PMID- 24093085
TI  - Dopaminergic innervation of the human subventricular zone: a comparison between
      Huntington's chorea and Parkinson's disease.
AB  - The subventricular zone retains its neurogenic capacity throughout life and, as
      such, is often considered a potential source for endogenous repair in
      neurodegenerative disorders. Because dopamine is believed to stimulate adult
      neurogenesis, we looked for possible variations in the dopaminergic innervation
      of the subventricular zone between cases of Huntington's chorea and Parkinson's
      diseases. Antibodies against tyrosine hydroxylase (TH) and proliferating cell
      nuclear antigen (PCNA) were used as specific markers of dopaminergic axons and
      cell proliferating activity, respectively. The immunohistochemical approach was
      applied to postmortem tissue from 2 Parkinson's disease cases, 4 Huntington's
      disease cases, along with age-matched controls. The immunostaining was revealed
      with either diaminobenzidine or fluorescent-conjugated secondary antibodies.
      Optical density measurements were made along the entire dorso-ventral extent of
      the caudate nucleus. An intense TH+ zone was detected along the ventricular
      border of the caudate nucleus in Huntington's disease cases, but not in patients
      with Parkinson's disease or age-matched controls. This thin (287+/-38 MUm)
      paraventricular zone was composed of numerous small and densely packed dopamine
      axon varicosities and overlapped the deep layers of the subventricular zone. Its
      immunoreactivity was 47+/-8% more intense than that of adjacent striatal areas.
      The dopamine innervation of the subventricular zone is strikingly massive in
      Huntington's chorea compared to Parkinson's disease, a finding that concurs with
      the marked increase in neurogenesis noted in the subventricular zone of
      Huntington's disease patients. This finding suggests that dopamine plays a
      crucial role in mechanisms designed to compensate for the massive striatal
      neuronal losses that occur in Huntington's disease. 

PMID- 24093081
TI  - Pathways to neurodegeneration: mechanistic insights from GWAS in Alzheimer's
      disease, Parkinson's disease, and related disorders.
AB  - The discovery of causative genetic mutations in affected family members has
      historically dominated our understanding of neurodegenerative diseases such as
      Alzheimer's disease (AD), Parkinson's disease (PD), frontotemporal dementia
      (FTD), and amyotrophic lateral sclerosis (ALS). Nevertheless, most cases of
      neurodegenerative disease are not explained by Mendelian inheritance of known
      genetic variants, but instead are thought to have a complex etiology with
      numerous genetic and environmental factors contributing to susceptibility.
      Although unbiased genome-wide association studies (GWAS) have identified novel
      associations to neurodegenerative diseases, most of these hits explain only
      modest fractions of disease heritability. In addition, despite the substantial
      overlap of clinical and pathologic features among major neurodegenerative
      diseases, surprisingly few GWAS-implicated variants appear to exhibit cross
      disease association. These realities suggest limitations of the focus on
      individual genetic variants and create challenges for the development of
      diagnostic and therapeutic strategies, which traditionally target an isolated
      molecule or mechanistic step. Recently, GWAS of complex diseases and traits have
      focused less on individual susceptibility variants and instead have emphasized
      the biological pathways and networks revealed by genetic associations. This new
      paradigm draws on the hypothesis that fundamental disease processes may be
      influenced on a personalized basis by a combination of variants - some common and
      others rare, some protective and others deleterious - in key genes and pathways.
      Here, we review and synthesize the major pathways implicated in
      neurodegeneration, focusing on GWAS from the most prevalent neurodegenerative
      disorders, AD and PD. Using literature mining, we also discover a novel
      regulatory network that is enriched with AD- and PD-associated genes and centered
      on the SP1 and AP-1 (Jun/Fos) transcription factors. Overall, this pathway- and
      network-driven model highlights several potential shared mechanisms in AD and PD
      that will inform future studies of these and other neurodegenerative disorders.
      These insights also suggest that biomarker and treatment strategies may require
      simultaneous targeting of multiple components, including some specific to disease
      stage, in order to assess and modulate neurodegeneration. Pathways and networks
      will provide ideal vehicles for integrating relevant findings from GWAS and other
      modalities to enhance clinical translation. 

PMID- 24093086
TI  - Peptides in receptor-mediated radiotherapy: from design to the clinical
      application in cancers.
AB  - Short peptides can show high affinity for specific receptors overexpressed on
      tumor cells. Some of these are already used in cancerology as diagnostic tools
      and others are in clinical trials for therapeutic applications. Therefore,
      peptides exhibit great potential as a diagnostic tool but also as an alternative
      or an additional antitumoral approach upon the covalent attachment of a
      therapeutic moiety such as a radionuclide or a cytotoxic drug. The chemistry
      offers flexibility to graft onto the targeting-peptide either fluorine or iodine
      directly, or metallic radionuclides through appropriate chelating agent. Since
      short peptides are straightforward to synthesize, there is an opportunity to
      further improve existing peptides or to design new ones for clinical
      applications. However, several considerations have to be taken into account to
      optimize the recognition properties of the targeting-peptide to its receptor, to
      improve its stability in the biological fluids and its residence in the body, or
      to increase its overall therapeutic effect. In this review, we highlight the
      different aspects which need to be considered for the development of an efficient
      peptide receptor-mediated radionuclide therapy in different neoplasms. 

PMID- 24093087
TI  - Coronary Calcium Scanning in Patients after Adjuvant Radiation for Early Breast
      Cancer and Ductal Carcinoma In situ.
AB  - BACKGROUND AND OBJECTIVE: Radiation therapy (RT) is part of standard adjuvant
      treatment for breast cancer. Earlier studies demonstrated increased cardiac
      morbidity and mortality from this. Coronary Calcium scanning utilizing
      Multidetector Computed Tomography (MDCT) can detect early atherosclerosis in
      coronary arteries by identifying the amount of calcifications. In our study we
      employed these tools to detect occult atherosclerosis at least 5 years following
      breast RT. METHODS: We evaluated 20 asymptomatic patients, <60 years old, treated
      with RT at least 5 years prior to enrollment. Nine received RT to the left and 11
      to the right chest wall. The median interval between RT and calcium scan was 8
      years. All patients were treated with external beam RT using tangential
      technique. All patients underwent MDCT to compute volumetric and Agatston calcium
      scores of the coronary arteries and the aorta. RESULTS: Eleven patients had RT to
      the right chest wall, and eight had a calcium score of 0, while two had minimally
      elevated scores and one patient had a significantly elevated score. Meanwhile
      nine patients had RT to the left chest wall, and seven had a calcium score of 0.
      None had significantly elevated scores. In the aorta, 11 of 20 patients had a
      score of 0, while 8 of 20 had minimally elevated scores. CONCLUSION: In contrast
      to studies demonstrating increased cardiovascular morbidity, our pilot study did
      not detect significant occult atherosclerosis using MDCT of the coronaries and
      aorta of patients assessed five or more years following radiation for treatment
      of breast cancer.

PMID- 24093088
TI  - Downregulation of 14q32 microRNAs in Primary Human Desmoplastic Medulloblastoma.
AB  - Medulloblastoma (MB) is one of the most common pediatric cancers, likely
      originating from abnormal development of cerebellar progenitor neurons. MicroRNA
      (miRNA) has been shown to play an important role in the development of the
      central nervous system. Microarray analysis was used to investigate miRNA
      expression in desmoplastic MB from patients diagnosed at a young age (1 or 2
      years old). Normal fetal or newborn cerebellum was used as control. A total of 84
      differentially expressed miRNAs (64 downregulated and 20 upregulated) were found.
      Most downregulated miRNAs (32/64) were found to belong to the cluster of miRNAs
      at the 14q32 locus, suggesting that this miRNA locus is regulated as a module in
      MB. Possible mechanisms of 14q32 miRNAs downregulation were investigated by the
      analysis of publicly available gene expression data sets. First, expression of
      estrogen-related receptor-gamma (ESRRG), a reported positive transcriptional
      regulator of some 14q32 miRNAs, was found downregulated in desmoplastic MB.
      Second, expression of the parentally imprinted gene MEG3 was lower in MB in
      comparison to normal cerebellum, suggesting a possible epigenetic silencing of
      the 14q32 locus. miR-129-5p (11p11.2/7q32.1), miR-206 (6p12.2), and miR-323-3p
      (14q32.2), were chosen for functional studies in DAOY cells. Overexpression of
      miR-129-5p using mimics decreased DAOY proliferation. No effect was found with
      miR-206 or miR-323 mimics. 

PMID- 24093090
TI  - Schwannoma in the upper limbs.
AB  - Schwannomas are the commonest tumours of peripheral nerves. Despite the classical
      description that schwannomas are well encapsulated and can be completely
      enucleated during excision, a portion of them have fascicular involvement and
      could not be completely shelled out. A retrospective review for 8 patients was
      carried out over 10 years. 75% of schwannoma occurred over the distal region of
      upper limb (at elbow or distal to it). It occurs more in the mixed nerve instead
      of pure sensory or motor nerve. 50% of patients had mixed nerve involvement.
      Fascicular involvement was very common in schwannoma (75% of patients). Removal
      of the tumour with fascicles can cause functional deficit. At present, there is
      no method (including preoperative MRI) which can predict the occurrence of
      fascicular involvement; the authors therefore proposed a new system to stratify
      patients who may benefit from interfascicular nerve grafts. In this group of
      patients, the authors strongly recommend that the possibility and option of nerve
      graft should be discussed with patients prior to schwannoma excision, so that
      nerve grafting could be directly proceeded with patient consent in case there is
      fascicular involvement of tumour found intraoperatively. 

PMID- 24093089
TI  - Getting to know ovarian cancer ascites: opportunities for targeted therapy-based
      translational research.
AB  - More than one third of ovarian cancer patients present with ascites at diagnosis,
      and almost all have ascites at recurrence. The presence of ascites correlates
      with the peritoneal spread of ovarian cancer and is associated with poor disease
      prognosis. Malignant ascites acts as a reservoir of a complex mixture of soluble
      factors and cellular components which provide a pro-inflammatory and tumor
      promoting microenvironment for the tumor cells. Subpopulations of these tumor
      cells exhibit cancer stem-like phenotypes, possess enhanced resistance to
      therapies and the capacity for distal metastatic spread and recurrent disease.
      Thus, ascites-derived malignant cells and the ascites microenvironment represent
      a major source of morbidity and mortality for ovarian cancer patients. This
      review focuses on recent advances in our understanding of the molecular,
      cellular, and functional characteristics of the cellular populations within
      ascites and discusses their contributions to ovarian cancer metastasis,
      chemoresistance, and recurrence. We highlight in particular recent translational
      findings which have used primary ascites-derived tumor cells as a tool to
      understand the pathogenesis of the disease, yielding new insights and targets for
      therapeutic manipulation. 

PMID- 24093091
TI  - Impact of interstitial pneumonia on the survival and risk factors analysis of
      patients with hematological malignancy.
AB  - BACKGROUND: The emergence of interstitial pneumonia (IP) in patients with
      hematological malignancy (HM) is becoming a challenging scenario in current
      practice. However, detailed characterization and investigation of outcomes and
      risk factors on survival have not been addressed. METHODS: We conducted a
      retrospective study of 42,584 cancer patients covering the period between 1996
      and 2008 using the institutional cancer registry system. Among 816 HM patients,
      61 patients with IP were recognized. The clinical features, laboratory results,
      and histological types were studied to determine the impact of IP on survival and
      identify the profile of prognostic factors. RESULTS: HM patients with IP showed a
      significant worse survival than those without IP in the 5-year overall survival
      (P = 0.027). The overall survival showed no significant difference between
      infectious pneumonia and noninfectious interstitial pneumonia (IIP versus nIIP)
      (P = 0.323). In a multivariate Cox regression model, leukocyte and platelet count
      were associated with increased risk of death. CONCLUSIONS: The occurrence of IP
      in HM patients is associated with increased mortality. Of interest, nIIP is a
      prognostic indicator in patients with lymphoma but not in patients with leukemia.
      However, aggressive management of IP in patients with HM is strongly advised, and
      further prospective survey is warranted.

PMID- 24093092
TI  - Particular Mal de Meleda phenotypes in Tunisia and mutations founder effect in
      the Mediterranean region.
AB  - Mal de Meleda (MDM) is a rare, autosomal recessive form of palmoplantar
      keratoderma. It is characterized by erythema and hyperkeratosis of the palms and
      soles that progressively extend to the dorsal surface of the hands and feet. It
      is caused by mutations in SLURP-1 gene encoding for secreted mammalian Ly-6/uPAR
      related protein 1 (SLURP-1). We performed mutational analysis by direct
      sequencing of SLURP-1 gene in order to identify the genetic defect in three
      unrelated families (families MDM-12, MDM-13, and MDM-14) variably affected with
      transgressive palmoplantar keratoderma. A spectrum of clinical presentations with
      variable features has been observed from the pronounced to the transparent
      hyperkeratosis. We identified the 82delT frame shift mutation in the SLURP-1 gene
      in both families MDM-12 and MDM-13 and the missense variation p.Cys99Tyr in
      family MDM-14. To date, the 82delT variation is the most frequent cause of MDM in
      the world which is in favour of a recurrent molecular defect. The p.Cys99Tyr
      variation is only described in Tunisian families making evidence of founder
      effect mutation of likely Tunisian origin. Our patients presented with very
      severe to relatively mild phenotypes, including multiple keratolytic pits
      observed for one patient in the hyperkeratotic area which was not previously
      reported. The phenotypic variability may reflect the influence of additional
      factors on disease characteristics. This report further expands the spectrum of
      clinical phenotypes associated with mutations in SLURP1 in the Mediterranean
      population. 

PMID- 24093093
TI  - Postmortem computed tomography imaging in the investigation of nontraumatic death
      in infants and children.
AB  - OBJECTIVE: To determine the accuracy of postmortem computed tomography (PMCT) for
      the assessment of causes in nontraumatic deaths in children. STUDY DESIGN: We
      enrolled cases of nontraumatic deaths of infants and children who underwent PMCT
      at a single center. The presumed cause of death determined by PMCT was
      prospectively compared with the clinical and pathological diagnoses of deaths.
      RESULTS: Thirty-eight cases were enrolled for analysis. Among them, seven cases
      also underwent conventional medical autopsy. PMCT revealed an identifiable cause
      of death in accordance with the clinical diagnosis of death in 16 cases of the 38
      cases (the concordance rate was 42%) and in accordance with the autopsy cause of
      death in four of the seven autopsy cases (the concordance rate was 57%). Among
      eight cases with unknown cause of death by clinical diagnosis, four cases (50%)
      were identified with cardiac tamponade as a cause of death (one case) and
      intracranial hemorrhage suggesting abuse (3 cases). CONCLUSIONS: PMCT seems to be
      a promising technique that might serve as a substitute for conventional medical
      autopsy and give us the complementary information to clinical diagnoses
      particularly in cases of child abuse. Larger multicenter trials are worthwhile to
      validate the general feasibility of PMCT.

PMID- 24093094
TI  - PDZ domains and viral infection: versatile potentials of HPV-PDZ interactions in
      relation to malignancy.
AB  - Cervical cancer is caused by high-risk human papillomaviruses (HPVs), and a
      unique characteristic of these is a PDZ (PSD-95/Dlg/[ZO-1-)binding motif in their
      E6 proteins. Through this motif HPV E6 interacts with a variety of PDZ domain
      containing proteins and targets them mainly for degradation. These E6-PDZ
      interactions exhibit extraordinarily different functions in relation to HPV
      induced malignancy, depending upon various cellular contexts; for example, Dlg
      and Scrib show different distribution patterns from what is seen in normal
      epithelium, both in localization and in amount, and their loss may be a late
      stage marker in malignant progression. Recent studies show that interactions with
      specific forms of the proteins may have oncogenic potential. In addition, it is
      interesting that PDZ proteins make a contribution to the stabilization of E6 and
      viral episomal maintenance during the course of HPV life cycle. Various
      posttranslational modifications also greatly affect their functions.
      Phosphorylation of hDlg and hScrib by certain kinases regulates several important
      signaling cascades, and E6-PDZ interactions themselves are regulated through PKA
      dependent phosphorylation. Thus these interactions naturally have great potential
      for both predictive and therapeutic applications, and, with development of
      screening tools for identifying novel targets of their interactions,
      comprehensive spatiotemporal analysis is currently underway.

PMID- 24093095
TI  - Dynamic of mutational events in variable number tandem repeats of Escherichia
      coli O157:H7.
AB  - VNTRs regions have been successfully used for bacterial subtyping; however, the
      hypervariability in VNTR loci is problematic when trying to predict the
      relationships among isolates. Since few studies have examined the mutation rate
      of these markers, our aim was to estimate mutation rates of VNTRs specific for
      verotoxigenic E. coli O157:H7. The knowledge of VNTR mutational rates and the
      factors affecting them would make MLVA more effective for epidemiological or
      microbial forensic investigations. For this purpose, we analyzed nine loci
      performing parallel, serial passage experiments (PSPEs) on 9 O157:H7 strains. The
      combined 9 PSPE population rates for the 8 mutating loci ranged from 4.4 * 10(
      05) to 1.8 * 10(-03) mutations/generation, and the combined 8-loci mutation rate
      was of 2.5 * 10(-03) mutations/generation. Mutations involved complete repeat
      units, with only one point mutation detected. A similar proportion between single
      and multiple repeat changes was detected. Of the 56 repeat mutations, 59% were
      insertions and 41% were deletions, and 72% of the mutation events corresponded to
      O157-10 locus. For alleles with up to 13 UR, a constant and low mutation rate was
      observed; meanwhile longer alleles were associated with higher and variable
      mutation rates. Our results are useful to interpret data from microevolution and
      population epidemiology studies and particularly point out that the inclusion or
      not of O157-10 locus or, alternatively, a differential weighting data according
      to the mutation rates of loci must be evaluated in relation with the objectives
      of the proposed study. 

PMID- 24093096
TI  - High expression of H3K27me3 is an independent predictor of worse outcome in
      patients with urothelial carcinoma of bladder treated with radical cystectomy.
AB  - It has been suggested that trimethylation of lysine 27 on histone H3 (H3K27me3)
      is a crucial epigenetic process in tumorigenesis. However, the expression pattern
      of H3K27me3 and its clinicopathological/prognostic significance in urothelial
      carcinoma of bladder (UCB) are unclear. In this study, upregulated expression of
      H3K27me3 protein was observed in the majority of UCBs by Western blotting. High
      expression of H3K27me3 was examined by IHC in 59/126 (46.8%) of UCB tissues and
      in 18/72 (25.0%) of normal urothelial bladder epithelial tissues (P = 0.002).
      High expression of H3K27me3 was associated with multifocal tumors and lymph node
      metastases (P < 0.05). Patients with high expression of H3K27me3 had shorter
      cancer-specific survival (CSS) time than patients with low expression of H3K27me3
      (P < 0.001). In different subsets of UCB patients, high expression of H3K27me3
      was also a prognostic indicator in patients with grade 2 and grade 3, pT1, pT2,
      pT3, and pN- disease (P < 0.05). Importantly, expression of H3K27me3 was an
      independent predictor for CSS (P < 0.001) of UCB patients treated with radical
      cystectomy (RC). Our data suggests that high expression of H3K27me3 is an
      independent molecular marker for predicting poor prognosis of UCB patients
      treated with RC. 

PMID- 24093098
TI  - Emergence in Western African countries of MDR-TB, focus on Cote d'Ivoire.
AB  - Tuberculosis (TB) is responsible for a high mortality rate (2.5%) worldwide,
      mainly in developing countries with a high prevalence of human immunodeficiency
      virus (HIV). The emergence of multiresistant strains of TB poses an extreme risk
      for TB outbreaks and highlights the need for global TB control strategies. Among
      Western African countries, Cote d'Ivoire (CI) represents a specific example of a
      country with great potential to prevent TB. Specifically, CI has a promising
      healthcare system for monitoring diseases, including vaccination programs.
      However, military and political conflict in CI favors the spread of infectious
      diseases, TB being among the most devastating. Compilation of the studies
      identifying common causes of TB would be extremely beneficial for the development
      of treatment and prevention strategies. Therefore, the purpose of this
      comprehensive review is to evaluate the epidemiology of TB in CI, describe the
      factors involved in pathogenesis, and suggest simple and applicable prevention
      strategies. 

PMID- 24093097
TI  - Progress of molecular targeted therapies for advanced renal cell carcinoma.
AB  - Vascular endothelial growth factor (VEGF) plays a crucial role in tumor
      angiogenesis. VEGF expression in metastatic renal cell carcinoma (mRCC) is mostly
      regulated by hypoxia, predominantly via the hypoxia-induced factor (HIF)/Von
      Hippel-Lindau (VHL) pathway. Advances in our knowledge of VEGF role in tumor
      angiogenesis, growth, and progression have permitted development of new
      approaches for the treatment of mRCC, including several agents targeting VEGF and
      VEGF receptors: tyrosine kinase pathway, serine/threonine kinases, alpha 5 beta 1
      integrin, deacetylase, CD70, mammalian target of rapamycin (mTOR), AKT, and
      phosphatidylinositol 3'-kinase (PI3K). Starting from sorafenib and sunitinib,
      several targeted therapies have been approved for mRCC treatment, with a long
      list of agents in course of evaluation, such as tivozanib, cediranib, and VEGF
      Trap. Here we illustrate the main steps of tumor angiogenesis process, defining
      the pertinent therapeutic targets and the efficacy and toxicity profiles of these
      new promising agents. 

PMID- 24093099
TI  - DNA methylation pyrosequencing assay is applicable for the assessment of
      epigenetic active environmental or clinical relevant chemicals.
AB  - Exposure of cells and organisms to stressors might result in epigenetic changes.
      Here it is shown that investigation of DNA methylation using pyrosequencing is an
      alternative for in vitro and in vivo toxicological testing of epigenetic effects
      induced by chemicals and drugs. An in vitro evaluation of global and CpG site
      specific DNA methylation upon treatment of cells with chemicals/drugs is shown.
      Bisulfite genomic sequencing of methylation controls showed high methylation of
      LINE1 in methylation positive control and low methylation in the negative
      controls. The CpG sites within the LINE1 element are methylated at different
      levels. In vitro cell cultures show a methylation level ranging from 56% to 49%.
      Cultures of drug resistant tumor cells show significant hypomethylation as
      compared with the originating nonresistant tumor cells. The in vitro testing of
      epigenetically active chemicals (5-methyl-2'-deoxycytidine and trichostatin A)
      revealed a significant change of LINE1 methylation status upon treatment, while
      specific CpG sites were more prone to demethylation than others (focal
      methylation). In conclusion, DNA methylation using pyrosequencing might be used
      not only for testing epigenetic toxins/drugs but also in risk assessment of
      drugs, food, and environmental relevant pollutants. 

PMID- 24093100
TI  - Control of respiratory motion by hypnosis intervention during radiotherapy of
      lung cancer I.
AB  - The uncertain position of lung tumor during radiotherapy compromises the
      treatment effect. To effectively control respiratory motion during radiotherapy
      of lung cancer without any side effects, a novel control scheme, hypnosis, has
      been introduced in lung cancer treatment. In order to verify the suggested
      method, six volunteers were selected with a wide range of distribution of age,
      weight, and chest circumference. A set of experiments have been conducted for
      each volunteer, under the guidance of the professional hypnotist. All the
      experiments were repeated in the same environmental condition. The amplitude of
      respiration has been recorded under the normal state and hypnosis, respectively.
      Experimental results show that the respiration motion of volunteers in hypnosis
      has smaller and more stable amplitudes than in normal state. That implies that
      the hypnosis intervention can be an alternative way for respiratory control,
      which can effectively reduce the respiratory amplitude and increase the stability
      of respiratory cycle. The proposed method will find useful application in image
      guided radiotherapy. 

PMID- 24093101
TI  - Biocompatible bacterial cellulose-poly(2-hydroxyethyl methacrylate) nanocomposite
      films.
AB  - A series of bacterial cellulose-poly(2-hydroxyethyl methacrylate) nanocomposite
      films was prepared by in situ radical polymerization of 2-hydroxyethyl
      methacrylate (HEMA), using variable amounts of poly(ethylene glycol) diacrylate
      (PEGDA) as cross-linker. Thin films were obtained, and their physical, chemical,
      thermal, and mechanical properties were evaluated. The films showed improved
      translucency compared to BC and enhanced thermal stability and mechanical
      performance when compared to poly(2-hydroxyethyl methacrylate) (PHEMA). Finally,
      BC/PHEMA nanocomposites proved to be nontoxic to human adipose-derived
      mesenchymal stem cells (ADSCs) and thus are pointed as potential dry dressings
      for biomedical applications. 

PMID- 24093102
TI  - Different impact of pretransplant anti-HLA antibodies detected by Luminex in
      highly sensitized renal transplanted patients.
AB  - It is well know that anti-HLA antibodies are an important obstacle in kidney
      transplantation. Our aim was to study the clinical impact of pretransplant donor
      specific anti-HLA antibodies (HLA-DSA), in highly sensitized (HS) patients. We
      analyzed retrospectively the day-of-transplant sera by Luminex Single Antigen
      Assay (LSA) in HS patients, and the results were correlated with episodes of
      humoral and cellular rejection as well as with graft and patient survival. All HS
      subjects received the same induction therapy and rejection episodes were biopsy
      proven. Thirteen patients (56.5%) preformed HLA-DSA, and we observed higher
      incidence of acute rejection in aforementioned patients than in the pre
      transplant negatives DSA recipients (77% versus 30%, P = 0.03). The one-year
      graft survival was significantly reduced in positive pre-transplant HLA-DSA
      patients (60% versus 100%, P = 0.01 Breslow). The positive predicted value of HLA
      DSA in relation to rejection reached 100% if patients lost their previous graft
      in the first year after transplant. Among anti-HLA antibodies present in patients
      before transplant, HLA-DSA were significantly associated with high risk of acute
      humoral and cellular rejection and reduced graft survival in posttransplant
      outcome. The negative impact of these antibodies was even higher when patients
      suffered an early loss of the previous transplant. 

PMID- 24093103
TI  - Probiotic potential and safety properties of Lactobacillus plantarum from Slovak
      Bryndza cheese.
AB  - One hundred and twenty-five acid-resistant presumptive lactobacilli were isolated
      from Slovak Bryndza cheese and screened for their antimicrobial activity against
      eight bacterial pathogens using spot agar assay. Out of twenty-six Lactobacillus
      strains with strong inhibition activity, twenty were identified as Lactobacillus
      plantarum and six as Lactobacillus fermentum. The most active eleven L. plantarum
      isolates were further characterized in vitro for some probiotic and safety
      properties. Only three isolates K10, K21, and ZS07 showed the ability to grow
      over 50% in the presence of 0.3% bile. Strong deconjugation efficiency was
      determined for CK06 and K21. The highest beta -galactosidase activity was shown
      in isolates ZS11, B01, CK06, and ZS07. Only three of the strains had the ability
      to produce tyramine: CK06, LM1, and ZS11. Strains K09, K21, ZS11, and ZS15 were
      susceptible to all tested antibiotics. Analysis of the results confirmed the L.
      plantarum isolates ZS07 and K21 as the most suitable for probiotic use, due to
      their desirable probiotic and safety characteristics. 

PMID- 24093104
TI  - Screening of a protein that interacts with the matrix attachment region-binding
      protein from Dunaliella salina.
AB  - We isolated the matrix attachment region-binding protein (MBP) DMBP-1 from
      Dunaliella salina in our previous studies. MBPs are part of the cis-acting
      protein family cluster. The regulatory function possibly works through the
      interaction of the MBPs with each other. In the present study, DMBP-1 was used as
      the bait in screening the D. salina cDNA library for DMBP-1 interactors that
      could potentially mediate the DMBP-1-regulated functions. A novel MBP, namely,
      DMBP-2, was identified as a DMBP-1 binding partner. The cDNA of DMBP-1 was 823 bp
      long and contained a 573 bp open reading frame, which encoded a polypeptide of
      191 amino acids. The interaction between DMBP-2 and DMBP-1 was further confirmed
      through glutathione S-transferase pull-down assays. 

PMID- 24093105
TI  - A fusion protein between streptavidin and the endogenous TLR4 ligand EDA targets
      biotinylated antigens to dendritic cells and induces T cell responses in vivo.
AB  - The development of tools for efficient targeting of antigens to antigen
      presenting cells is of great importance for vaccine development. We have
      previously shown that fusion proteins containing antigens fused to the extra
      domain A from fibronectin (EDA), an endogenous TLR4 ligand, which targets
      antigens to TLR4-expressing dendritic cells (DC), are highly immunogenic. To
      facilitate the procedure of joining EDA to any antigen of choice, we have
      prepared the fusion protein EDAvidin by linking EDA to the N terminus of
      streptavidin, allowing its conjugation with biotinylated antigens. We found that
      EDAvidin, as streptavidin, forms tetramers and binds biotin or biotinylated
      proteins with a Kd ~ 2.6 * 10(-14) mol/L. EDAvidin favours the uptake of
      biotinylated green fluorescent protein by DC. Moreover, EDAvidin retains the
      proinflammatory properties of EDA, inducing NF- kappabeta by TLR4-expressing
      cells, as well as the production of TNF- alpha by the human monocyte cell line
      THP1 and IL-12 by DC. More importantly, immunization of mice with EDAvidin
      conjugated with the biotinylated nonstructural NS3 protein from hepatitis C virus
      induces a strong anti-NS3 T cell immune response. These results open a new way to
      use the EDA-based delivery tool to target any antigen of choice to DC for
      vaccination against infectious diseases and cancer.

PMID- 24093106
TI  - Seroprevalence, detection of DNA in blood and milk, and genotyping of Toxoplasma
      gondii in a goat population in Italy.
AB  - Toxoplasma gondii is the causative agent of a major zoonosis with cosmopolitan
      distribution and is known to be transmitted mainly by the ingestion of
      undercooked or raw animal products. Drinking unpasteurized goat's milk is a risk
      factor associated with human toxoplasmosis. However, very little is known about
      the excretion of DNA in goat milk. Aim of the present study was to determine the
      seroprevalence of T. gondii infection using a modified agglutination test (MAT),
      to detect T. gondii DNA by nested-PCR (n-PCR) in samples of blood and milk from
      seropositive goats, and to genotype DNA isolates using 11 molecular markers in
      127 adult lactating goats from 6 farms in Italy. Positive MAT results were found
      in 60.6% of goats while 13% of blood and milk samples from seropositive goats
      were positive to n-PCR. A kappa coefficient of 1 indicated a perfect agreement
      between blood and milk n-PCR. Genetic characterization of isolates revealed the
      occurrence of genotype III (n = 7), genotype I (n = 1), and atypical genotypes
      with hints for genotype I (n = 2). Our results suggest that the risk of excretion
      of Toxoplasma tachyzoites might frequently occur in milk of seropositive goats
      testing positive to n-PCR on blood. 

PMID- 24093107
TI  - Oxidative stress and antimicrobial activity of chromium(III) and ruthenium(II)
      complexes on Staphylococcus aureus and Escherichia coli.
AB  - The prevalence of antibiotic resistance has resulted in the need for new
      approaches to be developed to combat previously easily treatable infections. The
      main aim of this work was to establish the potential of the synthetic alpha
      diimine chromium(III) and ruthenium(II) complexes (where the alpha-diimine
      ligands are bpy = 2,2-bipyridine, phen = 1,10-phenanthroline, and dppz =
      dipyrido[3,2-a:2',3'-c]-phenazine) like [Cr(phen)3](3+), [Cr(phen)2(dppz)](3+),
      [Ru(phen)3](2+), and [Ru(bpy)3](2+) as antibacterial agents by generating
      oxidative stress. The [Cr(phen)3](3+) and [Cr(phen)2(dppz)](3+) complexes showed
      activity against Gram positive and Gram negative bacteria with minimum inhibitory
      concentrations (MICs) ranging from 0.125 MUg/mL to 1 MUg/mL, while
      [Ru(phen)3](2+) and [Ru(bpy)3](2+) do not exhibit antimicrobial activity against
      the two bacterial genera studied at the concentration range used. When
      ciprofloxacin was combined with [Cr(phen)3](3+) for the inhibition of
      Staphylococcus aureus and Escherichia coli, an important synergistic effect was
      observed, FIC 0.066 for S. aureus and FIC 0.064 for E. coli. The work described
      here shows that chromium(III) complexes are bactericidal for S. aureus and E.
      coli. Our results indicate that alpha -diimine chromium(III) complexes may be
      interesting to open new paths for metallodrug chemotherapy against different
      bacterial genera since some of these complexes have been found to exhibit
      remarkable antibacterial activities.

PMID- 24093108
TI  - Bauhinia variegata leaf extracts exhibit considerable antibacterial, antioxidant,
      and anticancer activities.
AB  - The present study reports the phytochemical profiling, antimicrobial,
      antioxidant, and anticancer activities of Bauhinia variegata leaf extracts. The
      reducing sugar, anthraquinone, and saponins were observed in polar extracts,
      while terpenoids and alkaloids were present in nonpolar and ethanol extracts.
      Total flavonoid contents in various extracts were found in the range of 11-222.67
      mg QE/g. In disc diffusion assays, petroleum ether and chloroform fractions
      exhibited considerable inhibition against Klebsiella pneumoniae. Several other
      extracts also showed antibacterial activity against pathogenic strains of E.
      coli, Proteus spp. and Pseudomonas spp. Minimum bactericidal concentration (MBC)
      values of potential extracts were found between 3.5 and 28.40 mg/mL. The lowest
      MBC (3.5 mg/mL) was recorded for ethanol extract against Pseudomonas spp. The
      antioxidant activity of the extracts was compared with standard antioxidants.
      Dose dependent response was observed in reducing power of extracts. Polar
      extracts demonstrated appreciable metal ion chelating activity at lower
      concentrations (10-40 MUg/mL). Many extracts showed significant antioxidant
      response in beta carotene bleaching assay. AQ fraction of B. variegata showed
      pronounced cytotoxic effect against DU-145, HOP-62, IGR-OV-1, MCF-7, and THP-1
      human cancer cell lines with 90-99% cell growth inhibitory activity. Ethyl
      acetate fraction also produced considerable cytotoxicity against MCF-7 and THP-1
      cell lines. The study demonstrates notable antibacterial, antioxidant, and
      anticancer activities in B. variegata leaf extracts.

PMID- 24093109
TI  - The effect of very high versus very low sustained loading on the lower back and
      knees in middle life.
AB  - To evaluate the effect of the extremes of long term high and low physical
      activities on musculoskeletal heath in middle age, a historical cohort study was
      performed. The MRI knee and back findings of 25 randomly selected subjects who
      were inducted into the armed forces in 1983 and served at least 3 years as elite
      infantry soldiers were compared 25 years later, with 20 randomly selected
      subjects who were deferred from army service for full time religious studies at
      the same time. Both cohorts were from the same common genome. The two primary
      outcome measures were degenerative lumbar disc disease evaluated by the Pfirrmann
      score and degenerative knee changes evaluated by the WORMS score. At the 25-year
      follow up, the mean Pfirrmann score (8.6) for the L1 to S1 level of the elite
      infantry group was significantly higher than that of the sedentary group (6.7),
      (P = 0.003). There was no statistically significant difference between the WORMS
      knee scores between the two cohorts (P = 0.7). In spite of the much greater
      musculoskeletal loading history of the elite infantry cohort, only their lumbar
      spines but not their knees showed increased degenerative changes at middle age by
      MRI criteria. 

PMID- 24093110
TI  - Urinary IgG and alpha2-macroglobulin are powerful predictors of outcome and
      responsiveness to steroids and cyclophosphamide in idiopathic focal segmental
      glomerulosclerosis with nephrotic syndrome.
AB  - OBJECTIVE: To assess whether high-molecular-weight proteins excretion predicts
      outcome and therapy-responsiveness in patients with FSGS and nephrotic syndrome.
      RESEARCH DESIGN AND METHODS: Thirty-eight patients measured at biopsy fractional
      excretion of IgG (FEIgG) and urinary alpha2-macroglobulin/creatinine ratio (
      alpha m/C). Low and high risk groups were defined by cutoffs assessed by ROC
      analysis. In all patients first-line therapy was with steroids alone or in
      combination with cyclophosphamide. RESULTS: alpha2m/C and FEIgG were correlated
      with segmental sclerosis (r = 0.546; r = 0.522). Twenty-three patients (61%)
      entered Remission and 9 (24%) progressed to ESRD. Comparing low and high risk
      groups, by univariate analysis remission was predicted by FEIgG (77% versus 25%,
      P = 0.016) and alpha2m/C (81% versus 17%, P = 0.007) and ESRD at best by FEIgG
      (0% versus 75%, P < 0.0001) and alpha2m/C (4% versus 67%, P < 0.0001). By
      multivariate analysis FEIgG was the only independent predictor of remission and
      alpha2m/C the most powerful predictor of ESRD. Low and high risk groups of FEIgG
      and alpha2m/C in combination had very high predictive value of sustained
      remission and ESRD in response to therapy. CONCLUSIONS: FEIgG and alpha2m/C are
      powerful predictors of outcome and responsiveness to steroids and
      cyclophosphamide; their predictive value, if validated in prospective studies,
      may be useful in clinical practice suggesting first-line alternative treatments
      in high risk patients.

PMID- 24093111
TI  - Electrical impedance spectroscopy as electrical biopsy for monitoring radiation
      sequelae of intestine in rats.
AB  - Electrical impedance is one of the most frequently used parameters for
      characterizing material properties. The resistive and capacitive characteristics
      of tissue may be revealed by electrical impedance spectroscopy (EIS) as
      electrical biopsy. This technique could be used to monitor the sequelae after
      irradiation. In this study, rat intestinal tissues after irradiation were
      assessed by EIS system based on commercially available integrated circuits. The
      EIS results were fitted to a resistor-capacitor circuit model to determine the
      electrical properties of the tissue. The variations in the electrical
      characteristics of the tissue were compared to radiation injury score (RIS) by
      morphological and histological findings. The electrical properties, based on
      receiver operation curve (ROC) analysis, strongly reflected the histological
      changes with excellent diagnosis performance. The results of this study suggest
      that electrical biopsy reflects histological changes after irradiation. This
      approach may significantly augment the evaluation of tissue after irradiation. It
      could provide rapid results for decision making in monitoring radiation sequelae
      prospectively. 

PMID- 24093113
TI  - A posterior pneumothorax.

PMID- 24093112
TI  - Immunoglobulin G4-related lung disease: a disease with many different faces.
AB  - Immunoglobulin (Ig) G4-related lung disease is a fibroinflammatory entity that
      presents in protean ways. Diagnostically, IgG4-related lung disease requires a
      high clinical index of suspicion complemented by elevated serum IgG4 levels
      and/or biopsy that shows the characteristic pathological features. The disease is
      almost always responsive to systemic corticosteroids. However, relapse is common
      following their discontinuation. The authors present three cases to highlight the
      diverse clinical features, and to illustrate the diagnostic and therapeutic
      approaches to this disease. 

PMID- 24093114
TI  - Integrated interdisciplinary care for patients with chronic obstructive pulmonary
      disease reduces emergency department visits, admissions and costs: a quality
      assurance study.
AB  - BACKGROUND: Dedicated programs for the management of chronic obstructive
      pulmonary disease (COPD) can reduce hospitalizations and improve quality of life.
      OBJECTIVE: To investigate whether health care utilization could be reduced by a
      newly developed integrated, interdisciplinary initiative that included a COPD
      nurse navigator who educates patients and families, transitions patients through
      various points of care and integrates services. METHODS: The present quality
      assurance, pre-post study included patients followed by a COPD nurse navigator
      from January 25, 2010 to November 5, 2011. Information regarding emergency
      department visits and hospitalizations, including lengths of stay, were obtained
      from hospital databases. Diagnoses were classified as respiratory or
      nonrespiratory, and used primary and secondary hospitalization diagnoses to
      identify acute exacerbations of COPD (AECOPD). Paired sign tests were performed.
      RESULTS: The sample consisted of 202 patients. Following nurse navigator
      intervention, significantly more patients experienced a decrease in the number of
      respiratory-cause emergency department visits (P<0.05), number of respiratory
      hospitalizations (P<0.001), total hospital days for respiratory admissions
      (P<0.001), number of hospitalizations with AECOPD (P<0.001) and total hospital
      days for admissions with AECOPD (P<0.001). Financial modelling estimated annual
      savings in excess of $260,000. CONCLUSION: The present quality assurance study
      indicated that the implementation of an integrated interdisciplinary program for
      the care of patients with COPD can improve patient outcomes despite the tendency
      of COPD to worsen over time.

PMID- 24093115
TI  - Using a virtual game system to innovate pulmonary rehabilitation: safety,
      adherence and enjoyment in severe chronic obstructive pulmonary disease.
AB  - OBJECTIVE: The present pilot study tested the use of a virtual game system (VGS)
      for exercise training in patients with moderate to very severe chronic
      obstructive pulmonary disease undergoing pulmonary rehabilitation (PR). Safety,
      feasibility, enjoyment and adherence were assessed. METHODS: VGS (Wii [2006],
      Nintendo, USA) games were prescreened and categorized into lower- and upper-body
      workouts. Patients admitted for a three- to four-week inpatient PR program
      exercised daily. They were provided an opportunity to individually engage in VGS
      sessions three times weekly, varying with length of stay. Dyspnea, oxygen
      saturation and heart rate were measured before, during and after game sessions.
      Patients were considered to be adherent if they attended at least 50% of VGS
      sessions. Adverse events and enjoyment were evaluated. RESULTS: Thirty-two
      patients with a mean (+/- SD) age of 66+/-9 years and a mean forced expiratory
      volume in 1 s of 0.72+/-0.40 L participated. Among the 25 patients completing the
      program, adherence was 76%, with a mean attendance rate of 64+/-35%. Mean dyspnea
      score was 1.5+/-1.1 before and 3.2+/-1.2 after exercise. Mean oxygen saturation
      changed from 94+/-3% to 91+/-5% (P<0.001), while heart rate increased from 88+/
      15 beats/min to 102+/-18 beats/min (P<0.001). One patient reported chest pain
      requiring nitroglycerin spray and five experienced transient desaturation below
      85% with play. Patients enjoyed the program (visual analogue score 8+/-2.6/10)
      and most would highly recommend it to others. CONCLUSIONS: Moderate exercise
      using a VGS was safe, feasible and enjoyed as an adjunct to inpatient PR. This
      modality may encourage patients to maintain physical activity after PR.

PMID- 24093116
TI  - Tailored therapy in lung cancer.
AB  - Historically, all non-small cell lung cancers were essentially grouped together
      and considered to be a single disease. However, it is now recognized that non
      small cell lung cancer actually comprises a genetically diverse group of tumours.
      This, in turn, affords a new opportunity for the development of effective
      treatments tailored to individual tumours and patients. Advances in molecular
      biology have made possible the development of drugs against specific molecular
      targets on cancer cells, most notably the tyrosine kinase inhibitors. The
      relevant literature and current practice guidelines are discussed. In addition,
      other related areas of active investigation, including tumour vaccines and
      pharmacogenetics, are briefly reviewed. 

PMID- 24093117
TI  - 2013 Victor Chernick Award: Dr Jean-Guy Lapierre.

PMID- 24093118
TI  - Airway pressure release ventilation: a neonatal case series and review of current
      practice.
AB  - BACKGROUND: The use of airway pressure release ventilation (APRV) in very low
      birth weight infants is limited. OBJECTIVE: To report the authors' institutional
      experience and to review the current literature regarding the use of APRV in
      pediatric populations. METHODS: Neonates <1500 g ventilated using APRV from 2005
      to 2006 at McMaster Children's Hospital (Hamilton, Ontario) were retrospectively
      reviewed. Publications describing APRV in children from 1987 to 2011 were
      reviewed. RESULTS: Five infants, 24 to 28 weeks' gestational age, were ventilated
      using APRV. Indications for APRV were refractory hypoxemia (n=3), ventilatory
      dyssynchrony (n=1) and minimizing sedatives (n=1). All infants appeared to
      tolerate APRV well with no recorded adverse events. Current pediatric evidence
      regarding APRV is primarily observational. Published experience reveals that APRV
      settings in pediatrics often approximate those used in adults, thus deviating
      from the original guidelines recommended in children. Clinical outcomes, such as
      oxygenation, ventilation and sedation requirements, are inconsistent.
      CONCLUSIONS: APRV is primarily used as a rescue ventilation mode in children.
      Neonatal evidence is limited; however, the present study indicates that APRV is
      feasible in very low birth weight infants. There are unique considerations when
      applying this mode in small infants. Further research is necessary to confirm
      whether APRV is a safe and effective ventilation strategy in this population.

PMID- 24093119
TI  - Evolution of the COPD Assessment Test score during chronic obstructive pulmonary
      disease exacerbations: determinants and prognostic value.
AB  - BACKGROUND: An adequate evaluation of exacerbations is a primary objective in
      managing patients with chronic obstructive pulmonary disease (COPD). OBJECTIVES:
      To define the profile of health status recovery during severe exacerbations of
      COPD using the COPD Assessment Test (CAT) questionnaire and to evaluate its
      prognostic value. METHODS: Forty-five patients with previous COPD diagnoses who
      were hospitalized due to severe exacerbation(s) were included in the study. These
      patients were treated by their respective physicians following current
      recommendations; health status was assessed daily using the CAT questionnaire.
      The CAT score, spirometry and recurrent hospitalizations were recorded one and
      three months after hospital discharge. RESULTS: Global initiative for chronic
      Obstructive Lung Disease (GOLD) stage was an independent determinant for
      increased CAT score during the first days of exacerbation with respect to
      postexacerbation values. From hospitalization day 5, the CAT score was similar to
      that obtained in the stable phase. Body mass index, GOLD stage and education
      level were related to health status recovery pattern. CAT score increase and the
      area under the curve of CAT recovery were inversely related to the forced
      expiratory volume in 1 s achieved three months after discharge (r=-0.606; P<0.001
      and r=-0.532; P<0.001, respectively). Patients with recurrent hospitalizations
      showed higher CAT score increases and slower recovery. CONCLUSIONS: The CAT
      detects early health status improvement during severe COPD exacerbations. Its
      initial worsening and recovery pattern are related to lung function and recurrent
      hospitalizations.

PMID- 24093120
TI  - The analgesic efficacy of intra-articular acetaminophen in an experimental model
      of carrageenan-induced arthritis.
AB  - BACKGROUND: Acetaminophen is one of the most common drugs used for the treatment
      of pain and fever. OBJECTIVES: To examine the effects of intra-articular (IA)
      acetaminophen on carrageenan-induced arthritic pain-related behaviour and spinal
      c-Fos expression in rats. METHODS: The present study was performed using 20
      Sprague Dawley rats. Forty microlitres of IA 0.9% NaCl was injected in the
      control group, and 40 uL of IA carrageenan was injected in the carrageenan group.
      One hour after carrageenan injection, 400 ug of IA acetaminophen was injected in
      the IA acetaminophen group, and 400 ug of intraperitoneal (IP) acetaminophen was
      injected in the IP acetaminophen group. One day before injection, and 4 h and 8 h
      after injection, diameters of both knee joints, motility of the rat, paw loading
      and joint mobility were assessed. After the rats were euthanized, L3 and L4
      spinal segments were excised for c-Fos assessment. RESULTS: IA acetaminophen
      decreased both the severity and distribution of c-Fos expression. IP
      acetaminophen decreased only the distribution of c-Fos expression. IA
      acetaminophen decreased knee diameter at 8 h. IA and IP acetaminophen increased
      rat motility and paw loading scores. Joint mobility scores of IP acetaminophen
      were similar to saline at 8 h. CONCLUSIONS: Results of the present study indicate
      an analgesic and/or possible anti-inflammatory effect of IA acetaminophen and
      provide further evidence on the efficacy of systemic acetaminophen injection in
      reducing arthritic pain.

PMID- 24093121
TI  - A Delphi study to identify indicators of poorly managed pain for pediatric
      postoperative and procedural pain.
AB  - BACKGROUND: Adverse health care events are injuries occurring as a result of
      patient care. Significant acute pain is often caused by medical and surgical
      procedures in children, and it has been argued that undermanaged pain should be
      considered to be an adverse event. Indicators are often used to identify other
      potential adverse events. There are currently no validated indicators for
      undertreated pediatric pain. OBJECTIVES: To develop a preliminary list of
      indicators of undermanaged pain in hospitalized pediatric patients. METHODS: The
      Delphi technique was used to survey experts in pediatric pain management and
      quality improvement. The first round used an electronic questionnaire to ask: "In
      your opinion, what indicators would signify that acute pain in a child has not
      been adequately controlled?" Responses were grouped together in semantically
      similar themes, providing a list of possible adverse event indicators. Using this
      list, an electronic questionnaire was developed for round 2 asking respondents to
      indicate the importance of each potential indicator. RESULTS: All but one
      indicator achieved a level of consensus >=70%. Separate indicators emerged for
      postoperative and procedural pain. An additional distinction was made between
      indicators that could be identified by chart review and those requiring
      observation of practice and assessment from the child or parent. DISCUSSION: The
      adverse care indicators developed in the present study require further
      refinement. There is a need to test their clinical usability and to determine
      whether these indicators actually identify undermanaged pain in clinical
      practice. The present study is an important first step in identifying
      undermanaged pain in hospital and treating it as an adverse event. CONCLUSION:
      The adverse care indicators developed in the present study are the first step in
      conceptualizing mismanaged pain as an adverse event.

PMID- 24093122
TI  - Health care professionals' pain narratives in hospitalized children's medical
      records. Part 1: pain descriptors.
AB  - BACKGROUND: Although documentation of children's pain by health care
      professionals is frequently undertaken, few studies have explored the nature of
      the language used to describe pain in the medical records of hospitalized
      children. OBJECTIVES: To describe health care professionals' use of written
      language related to the quality and quantity of pain experienced by hospitalized
      children. METHODS: Free-text pain narratives documented during a 24 h period were
      collected from the medical records of 3822 children (0 to 18 years of age)
      hospitalized on 32 inpatient units in eight Canadian pediatric hospitals. A
      qualitative descriptive exploration using a content analysis approach was used.
      RESULTS: Pain narratives were documented a total of 5390 times in 1518 of the
      3822 children's medical records (40%). Overall, word choices represented
      objective and subjective descriptors. Two major categories were identified, with
      their respective subcategories of word indicators and associated cues: indicators
      of pain, including behavioural (e.g., vocal, motor, facial and activities cues),
      affective and physiological cues, and children's descriptors; and word
      qualifiers, including intensity, comparator and temporal qualifiers. CONCLUSIONS:
      The richness and complexity of vocabulary used by clinicians to document
      children's pain lend support to the concept that the word 'pain' is a label that
      represents a myriad of different experiences. There is potential to refine
      pediatric pain assessment measures to be inclusive of other cues used to identify
      children's pain. The results enhance the discussion concerning the development of
      standardized nomenclature. Further research is warranted to determine whether
      there is congruence in interpretation across time, place and individuals.

PMID- 24093123
TI  - Health care professionals' pain narratives in hospitalized children's medical
      records. Part 2: structure and content.
AB  - BACKGROUND: Although clinical narratives - described as free-text notations--have
      been noted to be a source of patient information, no studies have examined the
      composition of pain narratives in hospitalized children's medical records.
      OBJECTIVES: To describe the structure and content of health care professionals'
      narratives related to hospitalized children's acute pain. METHODS: All pain
      narratives documented during a 24 h period were collected from the medical
      records of 3822 children (0 to 18 years of age) hospitalized in 32 inpatient
      units in eight Canadian pediatric hospitals. A qualitative descriptive
      exploration using a content analysis approach was performed. RESULTS: Three major
      structural elements with their respective categories and subcategories were
      identified: information sources, including clinician, patient, parent, dual and
      unknown; compositional archetypes, including baseline pain status, intermittent
      pain updates, single events, pain summation and pain management plan; and
      content, including pain declaration, pain assessment, pain intervention and
      multidimensional elements of care. CONCLUSIONS: The present qualitative analysis
      revealed the multidimensionality of structure and content that was used to
      document hospitalized children's acute pain. The findings have the potential to
      inform debate on whether the multidimensionality of pain narratives' composition
      is a desirable feature of documentation and how narratives can be refined and
      improved. There is potential for further investigation into how health care
      professionals' pain narratives could have a role in generating guidelines for
      best pain documentation practice beyond numerical representations of pain
      intensity.

PMID- 24093125
TI  - Prolonged exposure of graphite oxide to soft X-ray irradiation during XPS
      measurements leads to alterations of the chemical composition.
AB  - X-ray photoelectron spectroscopy is an indispensable technique to analyse the
      structural and chemical features of graphene-based materials. Such detailed
      characterization is often imperative prior to the usage of these materials for
      various applications. In this work, the effects of the continuous irradiation
      with soft X-rays during the analysis of graphite oxide with X-ray photoelectron
      spectroscopy were investigated. Prolonged exposure to the X-ray source was
      observed to cause an overall decrease in the amount of oxygen-containing groups,
      which could consequently lead to the wrong interpretation of the XPS analysis
      result. Proper and careful consideration on the time span of XPS analysis of
      graphite oxide is, thus, highly advocated. 

PMID- 24093124
TI  - Does pain in individuals with multiple sclerosis affect employment? A systematic
      review and meta-analysis.
AB  - BACKGROUND: Individuals with multiple sclerosis (MS) experience some of the
      highest unemployment rates among all groups of chronic illnesses. Pain has been
      found to be a common reason for sick leave or early retirement in healthy
      populations or other groups with chronic illness; however, there is little
      awareness regarding the effect of pain on the work status of individuals with MS.
      OBJECTIVES: To estimate the extent to which individuals with pain differ in
      employment status compared with those without pain among MS patients. METHODS: An
      extensive systematic review of the scientific literature was performed within the
      framework of the Cochrane Collaboration to identify studies focusing on the
      effect of pain on employment in individuals with MS. The following databases were
      searched: PubMed, EMBASE, PsychInfo, Web of Science, MD Consult and Elsevier, and
      Science Direct. The methodological quality of studies was assessed using the
      McMaster Critical Review Form. RESULTS: Ten articles met the inclusion criteria
      and were included in the systematic review. Of these studies, five that exhibited
      clinical, methodological and statistical homogeneity were included in the meta
      analysis. The between-groups (pain + versus pain -) pooled random OR of being
      employed was 0.7 (strong), and was significantly different from unity (95% CI 0.5
      to 0.9; P=0.001). CONCLUSIONS: The results of the present study indicated that
      individuals with MS who experience pain were significantly more likely to report
      a decreased employment rate than individuals with MS who were pain free.

PMID- 24093126
TI  - Highly sensitive and selective fluorescent chemosensor for Ni(2+) based on a new
      poly(arylene ether) with terpyridine substituent groups.
AB  - A new poly(arylene ether) (PAET) with terpyridine substituent groups has been
      synthesized which shows a turn-off fluorescent response in the presence of Ni(2+)
      over other cations and allows discrimination of these cations from each other on
      the basis of the extent of quenching. 

PMID- 24093127
TI  - Development of a PCR-free electrochemical point of care test for clinical
      detection of methicillin resistant Staphylococcus aureus (MRSA).
AB  - An MRSA assay requiring neither labeling nor amplification of target DNA has been
      developed. Sequence specific binding of fragments of bacterial genomic DNA is
      detected at femtomolar concentrations using electrochemical impedance
      spectroscopy (EIS). This has been achieved using systematic optimisation of probe
      chemistry (PNA self-assembled monolayer film on gold electrode), electrode film
      structure (the size and nature of the chemical spacer) and DNA fragmentation, as
      these are found to play an important role in assay performance. These sensitivity
      improvements allow the elimination of the PCR step and DNA labeling and
      facilitate the development of a simple and rapid point of care test for MRSA.
      Assay performance is then evaluated and specific direct detection of the MRSA
      diagnostic mecA gene from genomic DNA, extracted directly from bacteria without
      further treatment is demonstrated for bacteria spiked into saline (10(6) cells
      per mL) on gold macrodisc electrodes and into human wound fluid (10(4) cells per
      mL) on screen printed gold electrodes. The latter detection level is particularly
      relevant to clinical requirements and point of care testing where the general
      threshold for considering a wound to be infected is 10(5) cells per mL. By
      eliminating the PCR step typically employed in nucleic acid assays, using screen
      printed electrodes and achieving sequence specific discrimination under ambient
      conditions, the test is extremely simple to design and engineer. In combination
      with a time to result of a few minutes this means the assay is well placed for
      use in point of care testing. 

PMID- 24093128
TI  - The challenge of applying Raman spectroscopy to monitor recombinant antibody
      production.
AB  - UV resonance Raman (UVRR) spectroscopy combined with chemometric techniques was
      investigated as a physiochemical tool for monitoring secreted recombinant
      antibody production in cultures of Chinese hamster ovary (CHO) cells. Due to the
      enhanced selectivity of the UVRR, spectral variations arising from protein, small
      molecule substrates, and nucleic acid medium components could be measured
      simultaneously and we have successfully determined antibody titre. Medium samples
      were taken during culture of three CHO cell lines: two antibody-producing cell
      lines and a non-producing cell line, and analysed by UVRR spectroscopy using an
      excitation laser of 244 nm. Principal component analysis (PCA) was applied to the
      spectral sets and showed a linear trend over time for the antibody-producing cell
      lines that was not observed in the non-producing cell line. Partial least squares
      regression (PLSR) was used to predict antibody titres, glucose utilization and
      lactate accumulation, and compared very favourably with gold standard data
      acquired with the much slower techniques of ELISA and liquid chromatography.
      Further analysis of the UVRR spectral sets using two-dimensional correlation
      moving windows also revealed that spectral variations due to protein and nucleic
      acid concentrations in the medium during cell culture varied between each of the
      three cell lines investigated. 

PMID- 24093129
TI  - Outcomes of transoral laser microsurgery for recurrent head and neck cancer.
AB  - OBJECTIVE: To report our outcomes with salvage CO2 laser surgery following
      recurrence of laryngeal and oropharyngeal cancer after radiotherapy. METHOD: This
      study entailed a prospective review of patients treated with transoral laser
      microsurgery for recurrent laryngeal and oropharyngeal cancer between 2002 and
      2010 at the Queen Elizabeth II Health Science Centre in Canada. RESULTS: Sixteen
      patients were identified, with a mean follow up of 30.6 months. Five patients
      died of recurrence. Complications were common in patients with oropharyngeal
      cancer. The overall survival and disease-free survival rates at an average of
      29.8 months follow up were 50 per cent and 68.8 per cent respectively.
      CONCLUSION: Salvage surgery using transoral laser microsurgery should be
      considered in the management of patients with recurrent laryngeal and
      oropharyngeal cancer. This technique offers acceptable salvage rates with less
      comorbidity than other treatments.

PMID- 24093132
TI  - Molecular epidemiology of extended-spectrum beta-lactamases and Escherichia coli
      isolated from retail foods including chicken meat in Japan.
AB  - Contamination of retail meat with extended-spectrum beta-lactamase (ESBL)
      producing Escherichia coli has been reported, but only limited data have been
      documented in Japan. One hundred fifty-three retail foods including chicken meat,
      beef, pork, and vegetables were purchased from 29 supermarkets between January
      and October in 2010. ESBL producers were recovered from each food sample using
      McConkey agar plate supplemented with 1 mg/L of cefotaxime. ESBL type was
      identified by DNA sequencing analysis after polymerase chain reaction
      amplification. Antibiogram, O serotype, plasmid replicon type, pulsotype, and
      multilocus sequence type were also determined. Fifty-two epidemiologically
      unrelated Escherichia coli isolates producing ESBL were recovered from 35 (22.9%)
      of 153 samples, all of which were chicken meat. ESBL types were mainly CTX-M-2
      group followed by CTX-M-1 group and CTX-M-8 group. The numbers of bacterial
      isolates (8 of 21, 38.1%) harboring bla(CTX-M-8) recovered from imported meat
      samples were significantly larger than those of domestic ones (one of 31, 3.2%)
      (p<0.05). Nine O serotypes (mainly O8, O25, and O1) were found, together with O
      antigen untypable (OUT). Four E. coli belonging to the O25b:H4-ST131 clone were
      recovered from domestic (n=1) and imported meat samples (n=3), respectively.
      These four isolates were susceptible to fluoroquinolones, although the E. coli
      O25b:H4-ST131 clone producing CTX-M-15, which is predominant in human isolates,
      is usually resistant to fluoroquinolones. By contrast, five CTX-M-15-producing E.
      coli strains were recovered only from domestic meat samples, and their serotypes
      were O8 or OUT instead of predominant serotype O25b. Our results showed that ESBL
      producing E. coli isolates recovered from retail chicken meat samples in Japan
      are generally divergent in both genetic and serological aspects. Further
      comparative analyses of bla(CTX-M)-mediating genetic elements would be continued
      in the next step to characterize the ESBL producers from retail foods in Japan.

PMID- 24093133
TI  - Anodic reactivity of ferrous sulfide precipitates changing over time due to
      particulate speciation.
AB  - The disposal of ferric phosphate (FePO4) sludge, routinely generated in
      wastewater and drinking water treatment, has a major impact on the overall
      treatment cost. Iron sulfide (FeSx) precipitation via sulfide addition to ferric
      phosphate (FePO4) sludge has been proven to be an effective method for phosphate
      recovery. Electrochemical oxidation of FeSx can then be utilized to recover
      ferric iron for reuse back in the phosphate removal process. In this study, the
      reactivity of FeSx particles for anodic oxidation at pH 4 was studied as a
      function of time after FeSx precipitate generation at a S/Fe molar ratio of 1.75.
      Cyclic voltammetry showed high reactivity for fresh FeSx particles, but the
      reactivity diminished significantly over a period of 1 month. X-ray absorption
      spectroscopy (XAS) revealed that this reduced reactivity with time is a
      consequence of the transformation of the FeSx particles in suspension from
      mackinawite (FeS) to pyrite (FeS2). 

PMID- 24093134
TI  - Ultrafast photoconductivity of graphene nanoribbons and carbon nanotubes.
AB  - We present a comparative study of the ultrafast photoconductivity in two
      different forms of one-dimensional (1D) quantum-confined graphene nanostructures:
      structurally well-defined semiconducting graphene nanoribbons (GNRs) fabricated
      by a "bottom-up" chemical synthesis approach and semiconducting carbon nanotubes
      (CNTs) with a similar bandgap energy. Transient photoconductivities of both
      materials were measured using time-resolved terahertz spectroscopy, allowing for
      contact-free measurements of complex-valued photoconductivity spectra with
      subpicosecond time-resolution. We show that, while the THz photoresponse seems
      very different for the two systems, a single model of free carriers experiencing
      backscattering when moving along the long axis of the CNTs or GNRs provides a
      quantitative description of both sets of results, revealing significantly longer
      carrier scattering times for CNTs (ca. 150 fs) than for GNRs (ca. 30 fs) and in
      turn higher carrier mobilities. This difference can be explained by differences
      in band structures and phonon scattering and the greater structural rigidity of
      CNTs as compared to GNRs, minimizing the influence of bending and/or torsional
      defects on the electron transport. 

PMID- 24093135
TI  - Adherence to American Heart Association and American College of Cardiology
      standard guidelines of angiography in Shiraz, Iran.
AB  - BACKGROUND AND OBJECTIVES: Coronary angiography is the most accurate and standard
      method for investigating the anatomic status and blood supply to the heart
      tissue; however, this method has been overused during the past decade. The
      present study aimed to investigate the appropriateness of coronary angiography in
      the patients referred to the selected hospital clinics in Shiraz, Iran. METHODS:
      This study included 280 outpatients who were referred to seven selected hospitals
      of Shiraz for coronary angiography. In order to collect the data regarding the
      patients and the angiography use, a questionnaire and a checklist were utilized.
      All the analyses were performed in SPSS, version 15. RESULTS: Among 280
      angiography cases, 206 (73.6%), 34 (12.2%), and 40 (14.3%) cases were considered
      as appropriate, uncertain, and inappropriate, respectively. Due to the 40 cases
      of inappropriate use of angiography, 19000 US dollars have been imposed on the
      insurance organizations as well as the patients. CONCLUSION: Senior managers of
      healthcare centers are recommended to pay special attention to the performance of
      diagnostic as well as therapeutic procedures according to the reliable and
      standard guidelines. Besides, insurance organizations and other institutes which
      reimburse the expenses should consider the appropriateness of application of
      angiography as a basis for the imbursement.

PMID- 24093136
TI  - Prenatal diagnosis of beta-thalassemia in twin pregnancies in Iran.
AB  - OBJECTIVE: Prenatal diagnosis of beta-thalassemia carrier couples has helped to
      prevent bearing affected children. Among 177 couples referred to our laboratory
      for prenatal diagnosis, 14 mothers had twin pregnancies.  METHODS: By using
      direct and indirect methods, we determined their mutations and linkage analysis
      using polymorphic markers (restriction fragment length polymorphism [RFLP]). 
      RESULTS:  It was shown that in five families both fetuses were heterozygote
      carriers. In another five families, one fetus was normal and the other one was
      carrier. In two families, one fetus was affected and the other one was
      heterozygous carrier; in one case one fetus was affected and the other one was
      homozygote normal. In the last family both fetuses were homozygote normal. If all
      fetuses were fraternal then one would expect to see seven homozygote normal and
      the same number affected, and 14 carriers. CONCLUSION: Our results indicated that
      at least in cases where both fetuses had identical genotypes, then they may be
      identical twins. Molecular testing indeed showed that in three cases the twins
      were identical. Another point is that in three cases, one of the twin fetuses was
      affected and the other one was either normal or heterozygote in which only the
      affected fetuses were aborted by the specialist.

PMID- 24093137
TI  - Characteristics of trauma in North East Iran and the prevention strategies.
AB  - BACKGROUND: The increase in mortality and morbidity of traumatized patients in
      developing countries might be due to disorganized medical services and credit
      tightness. This study was designed to describe the characteristics of injury, the
      strategies for the trauma prevention, and to improve the healthcare system. 
      METHODS: This was part of a national research project about trauma, conducted in
      the main trauma center of Mashhad, in North East Iran; it was a prospective cross
      sectional study which comprised of all consecutively admitted patients to the
      emergency department from December 2003 through July 2004.  RESULTS: Most of the
      traumatized patients were male, uneducated, housewives, or workers. Motor vehicle
      accidents (during the time when fastening seat belts and wearing helmets were not
      compulsory) and falling (height less than four meters and falling on the ground)
      were considered as the most common mechanisms. Almost 68.5% of the patients
      transferred to the hospitals did not have prehospital care. With an average
      injury severity score (ISS) value of 10.3, lower extremities and head and neck
      were the most common traumatized anatomic areas leading to their related
      morbidity and mortality.  CONCLUSION: A large number of traumatized cases among
      uneducated and nonoccupational population makes the role of mass media more
      prominent. Public education about traffic law, streets, and vehicle security
      check seems to be crucial to decrease the mortality and morbidity.

PMID- 24093138
TI  - Attitude and practice of pregnant women regarding self-medication in Yazd, Iran.
AB  - BACKGROUND: Medications, a main strategic commodity in any country, are strictly
      related to community health and sustainable development. Self-medication and
      irregular use of medications can increase their adverse effects. This study
      investigated the factors related to irregular and arbitrary use of medications in
      pregnant women admitted to health centers and clinics of Yazd, Iran, and their
      practice in this context. METHODS: This was a descriptive- analytic cross
      sectional study conducted among 180 pregnant women. Participants were selected by
      cluster sampling. We chose six health centers and clinics from all medical
      centers in Yazd by a simple random method. A questionnaire was completed by the
      pregnant women who were consecutively admitted to each center. Data were analyzed
      by ANOVA, t-test, Chi-square, and Pearson tests with SPSS-15 software. RESULTS:
      More than 35% of the women self-medicated during pregnancy. Women with academic
      degrees scored higher in the knowledge section; however, this difference was not
      significant.  The mean attitude scores for academic and nonacademic graduates
      were 34.92 (from 60) and 29.87, respectively while the mean practice scores were
      15 (from 20) and 14.25 for academic and non-academic graduates, respectively.
      CONCLUSION: The results of this study showed an increased prevalence of self
      medication among pregnant women. Because of potential fetomaternal hazards
      related to medications, it is necessary to conduct educational programs to
      prevent this harmful habit and attitude in pregnant women.

PMID- 24093139
TI  - Nonalcoholic fatty liver disease in a cluster of Iranian population: thyroid
      status and metabolic risk factors.
AB  - AIM: This study aimed to investigate the prevalence, metabolic risk factors, and
      thyroid dysfunction among a healthy urban population. METHODS: In a cross
      sectional study, the patients were evaluated for nonalcoholic fatty liver disease
      (NAFLD) using ultrasonography. The participants' characteristics such as age,
      sex, weight, height, body mass index (BMI), waist circumference, hip
      circumference, waist-to-hip ratio, systolic and diastolic blood pressure, and
      history of diabetes, ischemic heart disease (IHD), hypertension, and
      hyperlipidemia were recorded using a data gathering form. The patients were
      compared to those without NAFLD in terms of metabolic factors and thyroid
      abnormalities. RESULTS: From 832 participants, 127 (15.3%) individuals had NAFLD.
      Metabolic syndrome was detected in 39 participants (30.70 %) with NAFLD and in
      85 participants (12.05%) without NAFLD (P < 0.001) (OR: 3.22; 95 % CI: 2.07
      5.01). In multivariate logistic regression analysis BMI, waist-to-hip ratio, and
      higher serum ALT levels were independent predictors for NAFLD (P < 0.001). There
      was no statistically significant difference in serum TSH, free T4, and free T3
      levels between the participants with NAFLD and the participants without NAFLD (P
      > 0.05). Neither hypothyroidism nor markers of thyroid autoimmunity were
      associated with NAFLD in our study population (P > 0.05). Serum TSH was
      categorized according to 25th, 50th, and 75th percentile to <1.29 mIU/L, 1.29
      1.91 mIU/L, 1.91-2.77 mIU/L, and >2.77 mIU/L. Compared with non-NAFLD
      participants, the diagnosis of NAFLD was significantly higher in the low TSH
      group (P = 0.004). CONCLUSION: Central obesity as reflected by waist-to-hip ratio
      is one of the major risk factors for NAFLD. However, thyroid dysfunction was not
      correlated with NAFLD and the observed alterations in thyroid hormones are due to
      sick euthyroid syndrome.

PMID- 24093140
TI  - The Islamic Revolution of Iran and migration of physicians to the United States.
AB  - Following the Islamic Revolution of 1979 in Iran, the trend of migration of
      physicians from the country continued. The total number of Iranian physicians
      migrated to the United States (US) increased from 1625 before revolution in 1974,
      to 5045 in 2010, thirty years post-revolution. The percentage of medical
      graduates migrating to the US, in the same period dropped from 15% to 5%. The
      reasons for this drop were restrictions imposed, along with creation of good
      postgraduate residency and fellowship programs in Iran. Following the revolution,
      the number of medical schools increased from 13 to 48. Despite all the
      restrictions and impediments for post-revolution medical graduates, over 500
      medical graduates from newly established medical schools found their ways into
      the healthcare system of the US.     In spite of all hardships of eight years of
      imposed war, and 30 years of the US sanctions, Iran has been able to maintain
      good progress in its healthcare, education, and research in medicine and other
      branches of science and technology. 

PMID- 24093141
TI  - Induced abortion rate in Iran: a meta-analysis.
AB  - INTRODUCTION: About 44 million induced abortions take place worldwide annually,
      of which 50% are unsafe. The results of studies investigated the induced abortion
      rate in Iran are inconsistent. The aim of this meta-analysis was to estimate the
      incidence rate of induced abortion in Iran. METHODS: National and international
      electronic databases, as well as conference databases until July 2012 were
      searched. Reference lists of articles were screened and the studies' authors were
      contacted for additional unpublished studies. Cross-sectional studies addressing
      induced abortion in Iran were included in this meta-analysis. The primary outcome
      of interest was the induced abortion rate (the number of abortions per 1000 women
      aged 15-44 years in a year) or the ratio (the number of abortions per 100 live
      births in a year). The secondary outcome of interest was the prevalence of
      unintended pregnancies (the number of mistimed, unplanned, or unwanted
      pregnancies per total pregnancies). Data were analyzed using random effect
      models. RESULTS: Of 603 retrieved studies, using search strategy, 10 studies
      involving 102,394 participants were eventually included in the meta-analysis. The
      induced abortion rate and ratio were estimated as 8.9 per 1000 women aged 15-44
      years (95% CI: 5.46, 12.33) and 5.34 per 100 live births (95% CI: 3.61, 7.07),
      respectively. The prevalence of unintended pregnancy was estimated as 27.94 per
      100 pregnant women (95% CI: 23.46, 32.42). CONCLUSION: The results of this meta
      analysis helped a better understanding of the incidence of induced abortion in
      Iran compared to the other developing countries in Asia. However, additional
      sources of data on abortion other than medical records and survey studies are
      needed to estimate the true rate of unsafe abortion in Iran.

PMID- 24093142
TI  - Treatment outcome predictors in flexible dose-duration methadone detoxification
      program.
AB  - Methadone detoxification is among the widely used treatment programs for opioid
      dependence. The aims of this study were to identify which patient baseline
      factors and treatment regimen features are predictors of the treatment outcome in
      an outpatient flexible dose-duration methadone detoxification program.  We
      studied 126 opioid dependents in a naturalistic nonexperimental clinical setting.
      The patients were assessed for baseline demographic characteristics, and drug
      abuse characteristics. Treatment regimen features were recorded during the
      program. Successful treatment completion was defined as the last daily dose of
      methadone being less than 15 mg, negative urine analysis in the last two weeks of
      treatment, and based on the final clinician-client's decision.  Out of 126
      patients, 60 patients completed detoxification successfully. Younger age, longer
      duration of the opioid abuse, and higher subjective opiate intoxication severity
      before treatment entry were all significantly associated with negative treatment
      outcome. Among treatment regimen features, higher maximum methadone dose had a
      marginally significant independent effect on treatment failure. Patients with
      maximum methadone dose of more than 75 mg per day had around ten times worse
      success rate when compared to those who received lesser doses. The study findings
      could be used to predict treatment outcome and prognosis in a more individualized
      and patient-tailored approach in the real clinical setting. Guideline development
      for treatment selection and outcome monitoring in addiction medicine based on
      similar studies could enhance treatment outcome in clinical services. 

PMID- 24093143
TI  - Schistocytes, echinocytes, iron deficiency anemia, and thrombocytopenia -
      hematologic manifestations of splenic angiosarcoma.
AB  - Splenic angiosarcoma is a rare and aggressive malignancy with an incidence of
      less than one per million and a fatality rate over 90%.  Early diagnosis is of
      great importance for optimal management.  Here, we report the case of a patient
      with splenic angiosarcoma who presented with prominent schistocytes, echinocytes,
      thrombocytopenia, and iron deficiency anemia, which in combination with
      radiographic evidence of a splenic mass, raised the suspicion for angiosarcoma
      and resulted in a prompt surgical intervention with curative intent. Resolution
      of the hematologic findings following splenectomy suggests that patients with
      this malignancy should be monitored for recurrent hematologic abnormalities as
      they may herald recurrence of the disease. We present a literature review on the
      hematologic manifestations that is associated with this malignant disease. 

PMID- 24093144
TI  - Primary intracranial leiomyosarcoma.
AB  - Primary intracranial leiomyosarcomas are rare tumors that arise from the
      mesenchymal cells of the dura mater or cerebral blood vessels Here we report the
      case of an extra axial leiomyosarcoma in the right parieto-occipital region of a
      19-year-old male who had normal clinical and laboratory findings. Diagnostic
      imaging showed bony destruction, dural involvement and no parenchymal invasion.
      No primary site was found after metastasis work up. Specific serology tests were
      negative. The patient underwent a craniotomy, total tumor resection, duraplasty
      and skull reconstruction. He received radiotherapy and after 18 months of follow
      up, no clinical and radiological signs of recurrence have been found. 

PMID- 24093145
TI  - Plasmablastic lymphoma versus anaplastic myeloma in a human immunodeficiency
      virus negative male: a diagnostic quandary.
AB  - We report a 45-year-old male presenting with an intraoral mass originating from
      the right maxillary alveolar ridge. Radiologic investigations revealed osteolytic
      lesions in the right maxilla, skull, and lumbar vertebrae. This finding led to
      further investigations like electrophoresis of serum proteins for M band,
      quantitative estimation of immunoglobulins, urine electrophoresis for monoclonal
      light chain, and bone marrow biopsy. All these findings were inconclusive.
      Incision biopsy revealed the features of plasmacytoma. Since the other reports
      were incongruent with the histopathology report, for establishing a diagnosis of
      plasmacytoma, Immunohistochemistry of the specimen was done which revealed it to
      be a case of plasmablastic plasma cell neoplasm favoring plasmablastic lymphoma.
      The diagnostic confusion which arose in this setting is discussed in details. 

PMID- 24093146
TI  - Photoclinic. Juvenile Huntington disease.

PMID- 24093147
TI  - History of cancer in Iran.
AB  - The history of human and animal cancers date back to antiquity. The earliest
      written document on cancer appeared on Egyptian papyrus. For centuries, the
      theory of "four humors" was the primary hypothesis that explained the cause for
      cancer.  Finally, in the 19th century a new era began with the detection of the
      cellular origin of cancer; in due course, the nature of this lethal disease was
      better recognized and led to further achievements in cancer treatment. During the
      20th century researchers investigated several risk factors for cancer such as
      tobacco smoking and environmental chemicals, in addition to the carcinogenic role
      of certain viruses, occupational association of cancer, its relationship with
      certain hormones and dietary habits, and the genetic basis of cancer. These
      investigations resulted in more efficient cancer management. After the advent of
      radiotherapy and chemotherapy as two complementary therapeutic modalities to
      surgery, the campaign against cancer has improved. However, cancer remains a
      major health challenge that accounts for substantial morbidity and mortality
      worldwide. The present paper briefly reviews the history of cancer in Iran,
      particularly during the last decades of the 20th century. 

PMID- 24093148
TI  - Cephalhematoma and petechial rashes associated with acute parvovirus B19
      infection: a case report.
AB  - BACKGROUND: Parvovirus B19 can cause petechial rashes in the acute phase of
      illness as well as erythema infectiosum (fifth disease) during convalescence.
      This petechial rash is often called "gloves and socks" syndrome because of the
      typical distribution of the eruption. However, involvement of other sites (e.g.,
      intertriginous area) and generalized involvement have been recently recognized.
      We report here a patient with parvovirus-associated petechiae and cephalhematoma.
      CASE PRESENTATION: The patient was a previously healthy 10-year-old boy. There
      was a family history of fatal bleeding; his sister died of intracranial bleeding
      with an uncertain cause at the age of 5 months. The patient was admitted to our
      hospital because of sudden onset of cephalhematoma associated with fever. He
      reported that he had no recent head trauma but that he massaged his scalp on the
      day before admission. On admission, his temperature was 38.8 degrees C;
      otherwise, he was in a stable condition. Besides cephalhematoma, petechial rashes
      were present on his trunk and limbs. The initial laboratory tests were
      essentially normal, including platelet count and coagulation tests. Expanded
      laboratory tests were repeated to explore the etiology of his skin hemorrhage,
      all of which indicated that hematological disorders were unlikely. His symptoms
      subsided spontaneously over the next few days and he was discharged uneventfully.
      Anti-parvovirus IgM titer was elevated during hospitalization and typical
      erythema infectiosum was seen approximately 1 week after discharge. During 6
      months follow-up, he remained stable without recurrence of a hemorrhagic episode.
      Finally, we concluded that his cephalhematoma was responsible for acute
      parvoviral infection. CONCLUSIONS: This is believed to be the first report
      describing a possible association between parvovirus B19 infection and
      cephalhematoma. Parvovirus B19 infection should be considered in the differential
      diagnosis of children who present with unexplained hemorrhage such as
      cephalhematoma or petechiae.

PMID- 24093149
TI  - Potential use of chitosan nanoparticles for oral delivery of DNA vaccine in black
      seabream Acanthopagrus schlegelii Bleeker to protect from Vibrio
      parahaemolyticus.
AB  - To develop an effective and easy-to-administer vaccine against vibriosis of fish,
      the chitosan nanoparticles-loaded DNA vaccine against Vibrio parahaemolyticus was
      studied. A DNA vaccine was constructed using the outer membrane protein K (ompK)
      gene of V. parahaemolyticus strain (OS4) and pEGFP-N2 , a eukaryotic expression
      vector, and the construct was named pEGFP-N2 -OMPK (pDNA). The pDNA was
      encapsulated in chitosan particles (chitosan/pDNA). The effective diameter, mean
      diameter and polydispersity of the particles were 284.4 nm, 218.9 nm and 0.160,
      respectively. Scanning electron microscopy showed that the particles are
      dispersed as individual nanoparticles with spherical shape of around 200 nm and
      are homogeneously distributed. Encapsulation efficiency and loading percentage of
      nanoparticles were 91.5% and 2.08%, respectively. Reverse transcription
      polymerase chain reaction (RT-PCR) showed that RNA-containing information of the
      ompK gene existed in mid-intestine, liver, kidney and muscle 3 weeks after oral
      administration in black seabream Acanthopagrus schlegelii Bleeker. Expression of
      the reporter gene, green fluorescent protein (GFP), was observed in the above
      mentioned tissues by fluorescence microscopy. Expression of the ompK gene within
      3 weeks evoked an immune response. Black seabream was protected from V.
      parahaemolyticus (OS4), with 72.3% relative percentage survival (RPS) 3 weeks
      post-vaccination with chitosan/pDNA. The direct agglutination test indicated that
      oral administration with chitosan/pDNA induced an antibody immune response in
      fish against V. parahaemolyticus (OS4). Data obtained, here and in other related
      studies, suggest that chitosan nanoparticles are promising carriers for an oral
      pDNA vaccine. 

PMID- 24093150
TI  - Trends in poverty risks among people with and without limiting-longstanding
      illness by employment status in Sweden, Denmark, and the United Kingdom during
      the current economic recession--a comparative study.
AB  - BACKGROUND: Previous studies have found higher employment rates and lower risk of
      relative poverty among people with chronic illness in the Nordic countries than
      in the rest of Europe. However, Nordic countries have not been immune to the
      general rise in poverty in many welfare states in recent decades. This study
      analysed the trends in poverty risks among a particularly vulnerable group in the
      labour market: people with limiting-longstanding illness (LLSI), examining the
      experience of those with and without employment, and compared to healthy people
      in employment in Sweden, Denmark and the United Kingdom. METHODS: Cross-sectional
      survey data from EU-SILC (European Union Statistics on Income and Living
      Conditions) on people aged 25-64 years in Sweden, Denmark and the United Kingdom
      (UK) were analysed between 2005 and 2010. Age-standardised rates of poverty risks
      (<60% of national median equalised disposable income) were calculated. Odds
      ratios (ORs) of poverty risks were estimated using logistic regression. RESULTS:
      In all three countries, non-employed people with LLSI had considerably higher
      prevalence of poverty risk than employed people with or without LLSI. Rates of
      poverty risk in the UK for non-employed people with LLSI were higher than in
      Sweden and Denmark. Over time, the rates of poverty risk for Swedish non-employed
      people with LLSI in 2005 (13.8% CI=9.7-17.8) had almost doubled by 2010 (26.5%
      CI=19.9-33.1). For both sexes, the inequalities in poverty risks between non
      employed people with LLSI and healthy employed people were much higher in the UK
      than in Sweden and Denmark. Over time, however, the odds of poverty risk among
      British non-employed men and women with LLSI compared with their healthy employed
      counterparts declined. The opposite trend was seen for Swedish men: the odds of
      poverty risk for non-employed men with LLSI compared with healthy employed men
      increased from OR 2.8 (CIs=1.6-4.7) in 2005 to OR 5.3 (CIs=3.2-8.9) in 2010.
      CONCLUSIONS: The increasing poverty risks among the non-employed people with LLSI
      in Sweden over time are of concern from a health equity perspective. The role of
      recent Swedish social policy changes should be further investigated.

PMID- 24093151
TI  - Comparison of ReaxFF, DFTB, and DFT for phenolic pyrolysis. 2. Elementary
      reaction paths.
AB  - Reaction paths for the loss of CO, H2, and H2O from atomistic models of phenolic
      resin are determined using the hybrid B3LYP approach. B3LYP energetics are
      confirmed using CCSD(T). The energetics along the B3LYP paths are also evaluated
      using the PW91 generalized gradient approximation (GGA), the more approximate
      self-consistent charge density functional tight binding (SCC-DFTB), and the
      reactive force field (ReaxFF). Compared with the CCSD(T)/cc-pVTZ level for bond
      and reaction energies and barrier heights, the B3LYP, PW91, DFTB(mio), DFTB(pbc),
      and ReaxFF have average absolute errors of 3.8, 5.1, 17.4, 13.2, and 19.6
      kcal/mol, respectively. The PW91 is only slightly less accurate than the B3LYP
      approach, while the more approximate approaches yield somewhat larger errors. The
      SCC-DFTB paths are in better agreement with B3LYP than are those obtained with
      ReaxFF. 

PMID- 24093152
TI  - Comparative proteomics reveal diverse functions and dynamic changes of Bombyx
      mori silk proteins spun from different development stages.
AB  - Silkworms (Bombyx mori) produce massive amounts of silk proteins to make cocoons
      during the final stages of larval development. Although the major components,
      fibroin and sericin, have been the focus for a long time, few researchers have
      realized the complexity of the silk proteome. We collected seven kinds of silk
      fibers spun by silkworm larvae at different developmental stages: the silks spun
      by new hatched larvae, second instar day 0 larvae, third instar day 0 larvae,
      fourth instar day 0 larvae, and fourth instar molting larvae, the scaffold silk
      used to attach the cocoon to the substrate and the cocoon silk. Analysis by
      liquid chromatography-tandem mass spectrometry identified 500 proteins from the
      seven silks. In addition to the expected fibroins, sericins, and some known
      protease inhibitors, we also identified further protease inhibitors, enzymes,
      proteins of unknown function, and other proteins. Unsurprisingly, our
      quantitative results showed fibroins and sericins were the most abundant proteins
      in all seven silks. Except for fibroins and sericins, protease inhibitors,
      enzymes, and proteins of unknown function were more abundant than other proteins.
      We found significant change in silk protein compositions through development,
      being consistent with their different biological functions and complicated
      formation. 

PMID- 24093153
TI  - Reactive oxygen species play a critical role in collagen-induced platelet
      activation via SHP-2 oxidation.
AB  - AIMS: The collagen-stimulated generation of reactive oxygen species (ROS)
      regulates signal transduction in platelets, although the mechanism is unclear.
      The major targets of ROS include protein tyrosine phosphatases (PTPs). ROS
      mediated oxidation of the active cysteine site in PTPs abrogates the PTP
      catalytic activity. The aim of this study was to elucidate whether collagen
      induced ROS generation leads to PTP oxidation, which promotes platelet
      stimulation. RESULTS: SH2 domain-containing PTP-2 (SHP-2) is oxidized in
      platelets by ROS produced upon collagen stimulation. The oxidative inactivation
      of SHP-2 leads to the enhanced tyrosine phosphorylation of spleen tyrosine kinase
      (Syk), Vav1, and Bruton's tyrosine kinase (Btk) in the linker for the activation
      of T cells signaling complex, which promotes the tyrosine phosphorylation
      mediated activation of phospholipase Cgamma2 (PLCgamma2). Moreover, we found
      that, relative to wild-type platelets, platelets derived from glutathione
      peroxidase 1 (GPx1)/catalase double-deficient mice showed enhanced cellular ROS
      levels, oxidative inactivation of SHP-2, and tyrosine phosphorylation of Syk,
      Vav1, Btk, and PLCgamma2 in response to collagen, which subsequently led to
      increased intracellular calcium levels, degranulation, and integrin alphaIIbbeta3
      activation. Consistent with these findings, GPx1/catalase double-deficiency
      accelerated the thrombotic response in FeCl3-injured carotid arteries.
      INNOVATION: The present study is the first to demonstrate that SHP-2 is targeted
      by ROS produced in collagen-stimulated platelets and suggests that a novel
      mechanism for the regulation of platelet activation by ROS is due to oxidative
      inactivation of SHP-2. CONCLUSION: We conclude that collagen-induced ROS
      production leads to SHP-2 oxidation, which promotes platelet activation by
      upregulating tyrosine phosphorylation-based signal transduction.

PMID- 24093154
TI  - Identifying reaction modules in metabolic pathways: bioinformatic deduction and
      experimental validation of a new putative route in purine catabolism.
AB  - BACKGROUND: Enzymes belonging to mechanistically diverse superfamilies often
      display similar catalytic mechanisms. We previously observed such an association
      in the case of the cyclic amidohydrolase superfamily whose members play a role in
      related steps of purine and pyrimidine metabolic pathways. To establish a
      possible link between enzyme homology and chemical similarity, we investigated
      further the neighbouring steps in the respective pathways. RESULTS: We identified
      that successive reactions of the purine and pyrimidine pathways display similar
      chemistry. These mechanistically-related reactions are often catalyzed by
      homologous enzymes. Detection of series of similar catalysis made by succeeding
      enzyme families suggested some modularity in the architecture of the central
      metabolism. Accordingly, we introduce the concept of a reaction module to define
      at least two successive steps catalyzed by homologous enzymes in pathways
      alignable by similar chemical reactions. Applying such a concept allowed us to
      propose new function for misannotated paralogues. In particular, we discovered a
      putative ureidoglycine carbamoyltransferase (UGTCase) activity. Finally, we
      present experimental data supporting the conclusion that this UGTCase is likely
      to be involved in a new route in purine catabolism. CONCLUSIONS: Using the
      reaction module concept should be of great value. It will help us to trace how
      the primordial promiscuous enzymes were assembled progressively in functional
      modules, as the present pathways diverged from ancestral pathways to give birth
      to the present-day mechanistically diversified superfamilies. In addition, the
      concept allows the determination of the actual function of misannotated proteins.

PMID- 24093156
TI  - Parental cancer beliefs and trust in health information from medical authorities
      as predictors of HPV vaccine acceptability.
AB  - This research examines parental cancer beliefs and trust in health information
      from medical authorities as predictors of HPV vaccine acceptability.
      Specifically, the authors investigated how parents' perceived susceptibility to
      and severity of cancer, fatalistic beliefs about cancer prevention, and trust in
      health information from doctors/health professionals and government health
      agencies are related to willingness to vaccinate their daughters ages 11-12 years
      against HPV. The authors analyzed data from the 2007 Health Information National
      Trends Survey. The authors found that parents were more likely to accept the
      vaccine if they perceived a higher risk of getting cancer themselves and if they
      had a higher level of trust in health information from medical authorities.
      Perceived severity of cancer and fatalistic beliefs about cancer prevention did
      not predict vaccine acceptance. 

PMID- 24093157
TI  - The effect of emphasis and position on word identification by adult cochlear
      implant listeners.
AB  - This study examined the effect of emphasis and word position on word
      identification by postlingually deafened adult cochlear implant (CI) listeners (n
      = 20). These participants performed an identification task where Swedish (quasi-)
      minimal pairs were drawn from sentences and presented in a carrier sentence
      framework. It was found that emphasised stimuli were not identified more
      accurately than unemphasised stimuli. A regression analysis revealed a
      significant main effect for words drawn from the initial position in a sentence,
      however there was no interaction between original word position and emphasis.
      Post hoc analysis of the stimuli revealed that variations in the mean intensity
      of items arising from their original position in the sentence or emphasis status
      were unlikely to account for these results. These findings have implications for
      those who communicate regularly with CI listeners.

PMID- 24093155
TI  - Bench-to-bedside review: future novel diagnostics for sepsis - a systems biology
      approach.
AB  - The early, accurate diagnosis and risk stratification of sepsis remains an
      important challenge in the critically ill. Since traditional biomarker strategies
      have not yielded a gold standard marker for sepsis, focus is shifting towards
      novel strategies that improve assessment capabilities. The combination of
      technological advancements and information generated through the human genome
      project positions systems biology at the forefront of biomarker discovery. While
      previously available, developments in the technologies focusing on DNA, gene
      expression, gene regulatory mechanisms, protein and metabolite discovery have
      made these tools more feasible to implement and less costly, and they have taken
      on an enhanced capacity such that they are ripe for utilization as tools to
      advance our knowledge and clinical research. Medicine is in a genome-level era
      that can leverage the assessment of thousands of molecular signals beyond simply
      measuring selected circulating proteins. Genomics is the study of the entire
      complement of genetic material of an individual. Epigenetics is the regulation of
      gene activity by reversible modifications of the DNA. Transcriptomics is the
      quantification of the relative levels of messenger RNA for a large number of
      genes in specific cells or tissues to measure differences in the expression
      levels of different genes, and the utilization of patterns of differential gene
      expression to characterize different biological states of a tissue. Proteomics is
      the large-scale study of proteins. Metabolomics is the study of the small
      molecule profiles that are the terminal downstream products of the genome and
      consists of the total complement of all low-molecular-weight molecules that
      cellular processes leave behind. Taken together, these individual fields of study
      may be linked during a systems biology approach. There remains a valuable
      opportunity to deploy these technologies further in human research. The
      techniques described in this paper not only have the potential to increase the
      spectrum of diagnostic and prognostic biomarkers in sepsis, but they may also
      enable the discovery of new disease pathways. This may in turn lead us to
      improved therapeutic targets. The objective of this paper is to provide an
      overview and basic framework for clinicians and clinical researchers to better
      understand the 'omics technologies' to enhance further use of these valuable
      tools. 

PMID- 24093158
TI  - Evaluation of speech errors in Putonghua speakers with cleft palate: a critical
      review of methodology issues.
AB  - Speech errors associated with cleft palate are well established for English and
      several other Indo-European languages. Few articles describing the speech of
      Putonghua (standard Mandarin Chinese) speakers with cleft palate have been
      published in English language journals. Although methodological guidelines have
      been published for the perceptual speech evaluation of individuals with cleft
      palate, there has been no critical review of methodological issues in studies of
      Putonghua speakers with cleft palate. A literature search was conducted to
      identify relevant studies published over the past 30 years in Chinese language
      journals. Only studies incorporating perceptual analysis of speech were included.
      Thirty-seven articles which met inclusion criteria were analyzed and coded on a
      number of methodological variables. Reliability was established by having all
      variables recoded for all studies. This critical review identified many
      methodological issues. These design flaws make it difficult to draw reliable
      conclusions about characteristic speech errors in this group of speakers.
      Specific recommendations are made to improve the reliability and validity of
      future studies, as well to facilitate cross-center comparisons.

PMID- 24093159
TI  - Phonological development and prosodic units: evidence from metathesis errors.
AB  - There is general agreement in the literature that the ability to recognize that
      words are made up of "smaller phonological units" within the phonological
      hierarchy is a prerequisite for reading, however, there is still much debate as
      to which specific units are important. Many studies dealing with Japanese
      phonological development have been conducted, but most deal mainly with the mora
      unit, and few actually focus on other prosodic levels. In this paper, we will
      focus on the prosodic development of Japanese, with particular attention to the
      relationship of the different prosodic levels, namely, that of the foot, syllable
      and mora. The result of the reversal tasks seems to imply that the relationship
      between the foot and syllable units plays a role in the phonological processing
      of Japanese, implying the importance of focusing on phonological units other than
      the mora in order to correctly assess a child's phonological processing ability.

PMID- 24093160
TI  - Speech articulation performance of francophone children in the early school
      years: norming of the Test de Depistage Francophone de Phonologie.
AB  - Good quality normative data are essential for clinical practice in speech
      language pathology but are largely lacking for French-speaking children. We
      investigated speech production accuracy by French-speaking children attending
      kindergarten (maternelle) and first grade (premiere annee). The study aimed to
      provide normative data for a new screening test - the Test de Depistage
      Francophone de Phonologie. Sixty-one children named 30 pictures depicting words
      selected to be representative of the distribution of phonemes, syllable shapes
      and word lengths characteristic of Quebec French. Percent consonants' correct was
      approximately 90% and did not change significantly with age although younger
      children produced significantly more syllable structure errors than older
      children. Given that the word set reflects the segmental and prosodic
      characteristics of spoken Quebec French, and that ceiling effects were not
      observed, these results further indicate that phonological development is not
      complete by the age of seven years in French-speaking children.

PMID- 24093161
TI  - Responses to Wh-, Yes/No-, A-not-A, and choice questions in Taiwanese children
      with high-functioning autism spectrum disorder.
AB  - The present study investigated the hypothesis that children with high-functioning
      autism spectrum disorder (HFASD) have a greater difficulty in responding to Wh-
      than Yes/No questions across languages. Conversations between Taiwanese children
      and their mothers were investigated and the children's response adequacy to
      maternal questions in a semi-structured setting were examined. Twelve Taiwanese
      children with HFASD, ranging in age from 7.1 to 14.9 years old, were compared
      with 12 typically developing (TD) children matched on age, sex, IQ and mean
      length of utterance in syllable (MLUs). Compared to TD children, HFASD children
      produced more inadequate or inappropriate responses to Wh- and Yes/No questions
      than to A-not-A and Choice questions. Taiwanese HFASD children share a greater
      difficulty in responding to maternal Wh-questions with their Japanese
      counterparts and do not show a relative ease in responding to Yes/No questions,
      while A-not-A and Choice questions were easier to respond to for the Taiwanese
      children.

PMID- 24093162
TI  - Spoken language production in adults: examining age-related differences in
      syntactic complexity.
AB  - The use of complex syntax in the spoken discourse of young, middle-aged, and
      older adults was examined. The purpose of the study was to determine if syntactic
      complexity would show an age-related decline. Language samples were elicited from
      healthy adults in their 20 s, 40 s, and 60 s (n=20 per group) using a
      conversational (CON) task and a peer conflict resolution (PCT) task. Each sample
      was transcribed, segmented into utterances, and coded for main clauses and all
      types of finite and non-finite subordinate clauses. The results indicated that
      all groups produced greater syntactic complexity during the PCR task than the CON
      task as measured by mean length of utterance, clausal density, and the use of
      left-branching clauses. Additionally, the groups did not differ on any syntactic
      measures for either task. It is concluded that syntactic complexity in spoken
      discourse remains stable during the years that span early, middle, and later
      adulthood.

PMID- 24093163
TI  - Effects of comprehensive intervention on health-related quality of life in
      patients with chronic hepatitis B in China.
AB  - BACKGROUND: Hepatitis B virus (HBV) infection is a significant global health
      problem, especially in China. Chronic liver disease affects health related
      quality of life (HRQOL). The intervention method to improve HRQOL in patients
      with hepatitis B has been one-dimensional with inconsistent results. The purpose
      of this study was to evaluate the effect of comprehensive intervention on health
      related quality of life and provide guidance on improving HRQOL for patients with
      chronic hepatitis B. METHODS: Patients with chronic hepatitis B eligible for our
      study were randomly selected in three model regions of Jiangsu Province in June
      2010. 272 patients were invited and 254 took part, with a refusal rate of 6.62%.
      Comprehensive intervention included government support, technical guidance from
      the Chinese Centre for Disease Control and Prevention, standardised medical care,
      and community involvement. HRQOL before and 1 year after intervention was
      measured with the Short Form 36 and HBV-specific health surveys. Chi-square test,
      t-test and multiple linear regressive analyses were used. RESULTS: After
      comprehensive intervention, the HRQOL in patients with chronic hepatitis B showed
      significantly improvements in bodily pain, vitality, social functioning, and
      mental, as well as physical and mental component score (p < 0.05). Family and
      social support increased, and financial concerns decreased (p < 0.05). Marital
      status, duration of illness-related absence from work, education level, family
      financial status, and health insurance type were important factors affecting
      HRQOL change between the baseline and final assessment in patients with chronic
      hepatitis B. CONCLUSION: The comprehensive intervention was effective in
      improving the HRQOL of patients with chronic hepatitis B. TRIAL REGISTRATION:
      ChiCTR-OCH-12001882.

PMID- 24093164
TI  - Surgical management of hepatocellular carcinoma with tumor thrombi in the
      inferior vena cava or right atrium.
AB  - BACKGROUND: The prognosis for advanced hepatocellular carcinoma (HCC) with tumor
      thrombi in the inferior vena cava (IVC) or right atrium (RA) is poor, and there
      is no established effective treatment for this condition. Thus study aimed to
      evaluate the efficacy of surgical resection and prognosis after surgery for such
      cases. METHODS: Between January 1990 and December 2012, 891 patients underwent
      hepatectomy for HCC at our institution. Of these, 13 patients (1.5%) diagnosed
      with advanced HCC with tumor thrombi in the IVC or RA underwent hepatectomy and
      thrombectomy. Data detailing the surgical outcome were evaluated and recurrence
      free and overall survival rates were calculated using the Kaplan-Meier method.
      RESULTS: Seven patients had an IVC thrombus and six had an RA thrombus. Extra
      hepatic metastasis was diagnosed in 8 of 13 patients. Surgical procedures
      included three extended right lobectomies, three extended left lobectomies, five
      right lobectomies, and two sectionectomies. Right adrenal gland metastases were
      excised simultaneously in two patients. All IVC thrombi were removed under
      hepatic vascular exclusion and all RA thrombi were removed under cardiopulmonary
      bypass (CPB). Four patients (30.8%) experienced controllable postoperative
      complications, and there was no surgical mortality. The mean postoperative
      hospital stay for patients with IVC and RA thrombi was 23.6 +/- 12.5 days and
      21.2 +/- 4.6 days, respectively. Curative resection was performed in 5 of 13
      cases. The 1- and 3-year overall survival rates were 50.4%, and 21.0%,
      respectively, and the median survival duration was 15.3 months. The 1- and 3-year
      overall survival rates for patients who underwent curative surgical resection
      were 80.0% and 30.0%, respectively, with a median survival duration of 30.8
      months. All patients who underwent curative resection developed postoperative
      recurrences, with a median recurrence-free survival duration of 3.8 months. The 1
      year survival rate for patients who underwent noncurative surgery and had
      residual tumors was 29.2%, with a median survival duration of 10.5 months.
      CONCLUSIONS: Aggressive surgical resection for HCC with tumor thrombi in the IVC
      or RA can be performed safely and may improve the prognoses of these patients.
      However, early recurrence and treatment for recurrent or metastatic tumors remain
      unresolved issues.

PMID- 24093165
TI  - Gastrointestinal stromal tumors: molecular markers and genetic subtypes.
AB  - Mutation-activated signaling from the KIT and PDGFRA kinases has been
      successfully targeted in gastrointestinal stromal tumors (GISTs), with subtle
      differences between the mutations serving to refine prognosis and more precisely
      tailor therapy. There is a growing understanding of the molecular drivers of
      GISTs lacking mutations in KIT or PDGFRA, so called wild-type GISTs, further
      aiding in management decisions. This article provides an overview of all the
      known molecular subtypes of GIST and provides information about clinical
      correlates, treatment, and prognosis depending on the subtype. 

PMID- 24093166
TI  - Gastrointestinal stromal tumors: risk assessment and adjuvant therapy.
AB  - Adjuvant imatinib prolongs recurrence-free survival and probably overall survival
      of patients who have undergone surgery for gastrointestinal stromal tumor (GIST).
      Estimation of the risk of recurrence with a prognostication tool and tumor
      mutation analysis is essential before imatinib initiation, because approximately
      60% of patients with GIST with operable tumor are cured by surgery alone and some
      mutated tyrosine kinases are insensitive to imatinib. Adjuvant imatinib is
      usually administered for 3 years at the dose of 400 mg once daily. Early
      detection of tumors that recur despite adjuvant therapy with longitudinal imaging
      of the abdomen is likely beneficial.

PMID- 24093168
TI  - Treatment of localized sarcomas.
AB  - Surgery remains the only potentially curative therapy in the management of
      localized adult soft tissue sarcomas and gastrointestinal stromal tumors. There
      are over 50 different unique histologic types of soft tissue sarcomas, with
      different patterns of recurrence and prognosis. Surgical principles and
      sensitivity to locoregional and systemic treatments vary considerably based on
      the histologic type and anatomic location, as discussed in detail in this review.

PMID- 24093167
TI  - Gastrointestinal stromal tumors: management of metastatic disease and emerging
      therapies.
AB  - Gastrointestinal stromal tumors (GIST) are the most common mesenchymal tumors of
      the gastrointestinal tract. Before the advent of tyrosine kinase inhibitors
      (TKIs) there were few treatment options available to patients with metastatic
      GIST. Surgery was the mainstay of treatment and the prognosis was dismal. With
      the advent of imatinib and second-line TKIs the prognosis of metastatic GIST has
      improved dramatically; however, there is still a need for therapies for patients
      with disease refractory to TKI therapy. Newer agents are under investigation and
      may have promise. This article discusses the current standard of care in terms of
      standard and investigational pharmacotherapy in the management of metastatic
      GIST. 

PMID- 24093169
TI  - Liposarcomas.
AB  - Liposarcoma is one of the most common sarcoma subtypes with a heterogeneous
      biology and clinical behavior. This article gives a comprehensive overview on
      clinically relevant aspects of pathology and imaging. Prognostic factors and
      treatment strategies are discussed for different clinical situations and
      histologic subtypes. This information will be of value to clinicians and
      interdisciplinary sarcoma teams. 

PMID- 24093170
TI  - Leiomyosarcoma.
AB  - This article presents an overview of the current literature about the biology,
      pathology, and the clinical management of leiomyosarcoma. In addition, the
      article emphasizes and discusses the current systemic treatment options available
      for patients with leiomyosarcoma, which range from cytotoxic chemotherapy to
      target therapies. Particular leiomyosarcoma subtypes, such as uterine
      leiomyosarcoma and inferior vena cava leiomyosarcoma, are discussed separately. 

PMID- 24093171
TI  - Angiosarcomas and other sarcomas of endothelial origin.
AB  - Although benign hemangiomas are among the most common diagnoses among connective
      tissue tumors, angiosarcomas and other sarcomas arising from blood vessels are
      rare, even among sarcomas. Because endothelial tumors have unique embryonal
      derivation compared with other sarcomas, it is not surprising they have unique
      characteristics. Herein are reviewed some of these unique characteristics and
      therapeutic options for patients with some of these diagnoses, highlighting the
      potential of new agents for these tumors, which will in all likelihood also
      impact treatment on more common cancers. 

PMID- 24093172
TI  - Desmoid tumors: a comprehensive review of the evolving biology, unpredictable
      behavior, and myriad of management options.
AB  - Desmoid tumors are rare, clonal collections of benign fibrous tissue that exhibit
      a highly variable clinical course. This article presents a comprehensive review
      of desmoid tumors and summarizes the current literature pertaining to clinical
      presentation, diagnostic modalities, pathogenesis, prognostic factors, and
      management options. 

PMID- 24093173
TI  - Update in treatment and targets in Ewing sarcoma.
AB  - The improvement in outcome for patients with localized and metastatic Ewing
      sarcoma since the development of cytotoxic chemotherapy remains one of the most
      profound advances in oncology and one of the proudest achievements of sarcoma
      researchers. Identification of molecular targets for new treatments has become an
      intense area within Ewing sarcoma research. The development of improved
      preclinical Ewing sarcoma models and advanced molecular techniques will build on
      knowledge of EWS/FLI1 function, EWS/FLI1 transcription targets, and the other
      critical driver events in these tumors. 

PMID- 24093174
TI  - Update on targets and novel treatment options for high-grade osteosarcoma and
      chondrosarcoma.
AB  - Osteosarcoma and chondrosarcoma are the 2 most common malignant bone tumors. This
      review discusses the clinicopathologic features, recent preclinical developments,
      and targets currently being or to be validated in the clinic. 

PMID- 24093175
TI  - Targeted therapies in rare sarcomas: IMT, ASPS, SFT, PEComa, and CCS.
AB  - This article highlights the data currently available on the activity of targeted
      medical treatment in a subgroup of rare entities within soft tissue sarcomas,
      including inflammatory myofibroblastic tumor, alveolar soft part sarcoma,
      solitary fibrous tumor, malignant perivascular epithelioid cell tumor (PEComa),
      and clear cell sarcoma. 

PMID- 24093176
TI  - Emerging therapies for soft-tissue sarcomas.
AB  - Sarcomas are heterogeneous group of tumors that arise from tissues of mesenchymal
      origin. Current options for patients with advanced disease are limited, and only
      2 drugs have been approved for these diseases over the last decade. Although
      several drugs are currently under development for soft-tissue sarcoma as a whole,
      improved understanding of sarcoma biology has led to the emergence of subtype
      specific targeted therapy. This article reviews recent clinical data on emerging
      therapies for soft-tissue sarcoma. 

PMID- 24093177
TI  - Sarcoma.

PMID- 24093178
TI  - Microperimeters and microperimetry: new technology in ophthalmology with far
      reaching applications.

PMID- 24093179
TI  - Microperimetry and clinical practice: an evidence-based review.
AB  - Microperimeters embody technological abilities required to assess components of
      residual visual functions and functional vision. Residual visual functions and
      functional vision after macular vision loss are mostly defined by 3 major
      components: scotoma characteristics, preferred retinal loci (PRLs) and oculomotor
      control. Microperimetry may be proven superior as a method to standard automated
      perimetry (SAP) for residual visual function assessment. During microperimetry
      stimuli are projected directly on the retina with accurate test-retest of the
      same retinal point monitored by eye tracking technology. Microperimeters offer
      also abilities to determine accurately the location of a PRL. Recent research
      reveals also that fixation stability estimates in low vision cases are reliable
      predictors of visual acuity estimates. Fixation stability estimates provided
      automatically by the microperimeters are based on proprietary algorithms and
      provide reasonable estimates very close to BCEA values calculated from raw data.
      More and more microperimeters are used in clinical retina practice to assess more
      accurately the impact of diseases or of interventions on the retina.
      Microperimeters are also in use more often in glaucoma practices and it seems
      evident that the main usage for microperimeters is destined to monitor glaucoma
      damaged residual visual functions and functional vision. In addition
      identification of eccentric location of PRLs and fixation stability estimates at
      the PRL in low vision patients offers the LVR practitioner the option to use the
      best residual visual function available for rehabilitation. For mainstream
      ophthalmology many indicators point to the fact that microperimeters may take the
      lead role played by SAP in the last decades. For vision rehabilitation
      practitioners the advent of multiple choices for microperimetry portends the
      introduction of modern rehabilitation concepts in most clinical practices. Both
      developments seem to happen sooner, rather than later as expected by most.

PMID- 24093180
TI  - Fundus-driven perimetry (microperimetry) compared to conventional static
      automated perimetry: similarities, differences, and clinical applications.
AB  - Fundus-driven perimetry, commonly known as microperimetry, is a technique for
      measuring visual field sensitivity, whilst simultaneously viewing the fundus. In
      this article, we review the technique, focusing on the MP-1 microperimeter (Nidek
      Instruments, Inc, Padua, Italy); we compare it with conventional static automated
      perimetry, emphasizing the importance of understanding the effects of the
      different stimulus conditions and data analyses on the interpretation of
      microperimetry data. The clinical applications of the technique, in the
      evaluation of functional and structural changes that accompany retinal diseases,
      are illustrated by its use in patients with age-related macular degeneration,
      Stargardt disease, and retinitis pigmentosa. In addition, the advantages and
      limitations of the technique are summarized.

PMID- 24093181
TI  - Fixation stability as a goal in the treatment of macular disease.
AB  - Recent advances in the treatment of macular diseases have improved macular
      anatomy and function as measured and quantified by visual acuity, retinal
      thickness, and vascular changes detailed by fluorescein angiography. Such
      observed changes do not always explain improvement in visual function and do not
      always correlate with patient satisfaction. In some cases, there is poor
      correlation between anatomic changes and functional improvement. Microperimetry
      studies on fixation stability after treatment of macular diseases have shown a
      strong correlation between better fixation stability and visual acuity.
      Furthermore, achieving better fixation stability facilitates low-vision
      rehabilitation. These microperimetry findings suggest that fixation stability
      should be regarded as an important outcome measure in studies of macular disease
      treatment and should be considered in clinical and research studies of low-vision
      rehabilitation in cases of treated macular diseases.

PMID- 24093182
TI  - Preferred retinal locus profile during prolonged fixation attempts.
AB  - OBJECTIVE: The retinal area or location used during any fixation attempt defines
      the preferred retinal locus (PRL). It is presumed that during prolonged fixation
      attempts there may be various representative reference points within the PRL
      area. This study aims to clarify this presumption. DESIGN: Prospective,
      nonrandomized, observational case series. PARTICIPANTS: Sixty-five eyes of 41
      patients from the University of Nottingham, Queen's Medical Centre Retina and Low
      Vision Clinics. METHODS: A total of 65 eyes of 41 patients from the University of
      Nottingham, Queen's Medical Centre Retina and Low Vision Clinics were assessed
      for PRL using the Macular Integrity Assessment (MAIA) microperimetry equipment
      (CenterVue, Padova, Italy). The MAIA allows automatic calculation for 2 points
      named PRL_initial (PRLi), which is calculated after the first 10 seconds of
      fixation, and PRL_final (PRLf), which is calculated after the completion of all
      fixation attempts during the microperimetry test. RESULTS: Estimates of PRLi and
      PRLf were produced for all patients. Forty-six (71%) eyes were classified as
      having stable fixation; 40 of the 46 eyes (87%) had both PRLs location over the
      fovea centralis. Nineteen of 65 eyes (29%) were classified as having unstable or
      relatively unstable fixation; different PRLi and PRLf locations were found in 18
      (95%) of the 19 eyes, including 13 (68%) with central geographic atrophy
      secondary to dry age-related macular degeneration. The mean rate of change was
      5.3 units in fixation per unit change in distance in both PRLi and PRLf.
      CONCLUSIONS: The representative points during prolonged fixation attempts may
      vary at different stages of fixation. This is reflected in the characteristics of
      fixation stability of the patients and presents a possible association with main
      pathology responsible for low vision.

PMID- 24093183
TI  - Static and dynamic retinal fixation stability in microperimetry.
AB  - OBJECTIVE: To compare static (during a pure fixation task) versus dynamic (during
      microperimetry) quantification of fixation stability using microperimetry in
      normal and pathologic eyes, by means of 2 available (clinical and bivariate
      contour ellipse area [BCEA]) classification methods. DESIGN: Prospective
      comparative observational study. PARTICIPANTS: One hundred and forty-nine eyes
      (110 patients) with different macular diseases and 171 normal eyes (109
      subjects). METHODS: In all eyes studied, fixation stability was acquired during
      an isolated fixation task (static fixation) and during microperimetry (dynamic
      fixation). All fixation data were analyzed and compared by means of a clinical
      classification and by means of BCEA quantification. RESULTS: Pathologic eyes were
      classified as follows: 41 eyes with diabetic macular edema (DME group), 13 eyes
      with vitreoretinal interface disease, 60 eyes with age-related macular
      degeneration (AMD group), and 35 eyes with primary open-angle glaucoma. Fixation
      stability was not uniform among groups according to clinical classification in
      both static and dynamic modalities (p < 0.0001). AMD group showed larger BCEA
      areas compared with all other groups (p < 0.0001). All pathologic groups showed
      more unstable fixation in dynamic fashion according to both clinical and BCEA
      methods (p < 0.0001). The variation of fixation stability of control group in
      dynamic task was highlighted only by BCEA analysis (p < 0.0001). A deterioration
      of retinal fixation according to clinical method matches a significant increase
      in BCEA areas (p < 0.0001). CONCLUSIONS: The detection of clinical fixation
      stability changes improves when acquired in the dynamic modality. BCEA analysis
      provides more accurate evaluation of fixation stability and may detect minimal
      quantitative changes of the fixation area. However, a standard clinical
      classification can also detect changes in fixation stability in pathologic eyes.
      Both methods are useful tools in the evaluation of fixation stability.

PMID- 24093184
TI  - The worse eye is not as bad as it seems to be in AMD cases.
AB  - OBJECTIVE: It is the aim of this study to review residual vision in the less used
      eye of patients with age-related macular degeneration (AMD) using modern concepts
      for residual visual functions in addition to traditional methods for assessing
      visual acuity. DESIGN: The study was designed as a retrospective, nonrandomized,
      observational case series. PARTICIPANTS: Consecutive cases tested with
      microperimetry instruments were identified from archives. Included were cases
      with diagnosed AMD of all age groups and all visual acuity levels. METHODS: In
      all cases, microperimetric technology was used to assess residual visual
      function. Outcome measures selected for analysis were visual acuity, preferred
      retinal loci (PRL) topography, fixation stability, and PRL span. RESULTS: Data
      were collected and analyzed for both eyes from 51 patients with AMD low vision.
      There were 23 males and 28 females whose mean age was 84 (+/- 7) years. Within
      the group the difference in visual acuity estimates between the better seeing and
      the less used eye was statistically significant (p = 0.001). Similar positive
      statistical significant differences were noticed at all spatial frequencies
      (except at 6 cycles/degree) when testing contrast sensitivity. All other
      measurements were not statistically different between the better seeing and the
      poorer eye. This applies to the fixation stability and PRL span estimates. Almost
      half (49%) of the cases showed retinal noncorrespondence of PRLs between the 2
      eyes. CONCLUSIONS: Visual acuity estimates are not a reliable measure for
      residual vision. The less used eye in AMD cases has much better residual vision
      than thought before according to modern outcome measures. This new concept should
      be taken into account by all practitioners and be applied during all low vision
      rehabilitation interventions.

PMID- 24093185
TI  - Microperimetry, fundus autofluorescence, and retinal layer changes in progressing
      geographic atrophy.
AB  - OBJECTIVE: To analyze correlation among microperimetry, inner and outer retinal
      layers, and fundus autofluorescence (FAF) changes in eyes with progressing
      geographic atrophy (GA) secondary to age-related macular degeneration. METHODS:
      Microperimetry, spectral-domain optical coherence tomography (SD-OCT), standard
      short-wavelength FAF (SW-FAF), and near-infrared-wavelength FAF (NIR-FAF) were
      performed for all patients at both baseline and follow-up visits. FAF pattern,
      integrity of photoreceptor inner segment/outer segment (IS/OS) junction, total
      retinal thickness (RT), inner retinal layers (IRL), and outer retinal layers
      (ORL) thickness changes of every microperimetry extrafoveal tested point were
      analyzed. RESULTS: A total of 366 microperimetry tested points were analyzed (6
      patients, 7 eyes). Mean retinal sensitivity significantly decreased (p = 0.0149),
      and the percentage of dense scotomas significantly increased (p = 0.0125). Mean
      RT and mean ORL thickness significantly decreased (both p < 0.0001). Mean IRL
      thickness significantly increased (p = 0.0001). The decrease of ORL thickness was
      inversely correlated to the IRL thinning (rho = -0.710). FAF pattern at baseline
      was correlated to RT and ORL thickness (both p < 0.0001) and was significantly
      correlated to the risk to evolve to dense scotoma during follow-up (p = 0.0001 at
      SW-FAF, p < 0.0001 at NIR-FAF). Tested points showing at baseline the loss of
      photoreceptor IS/OS junction had a greater risk for evolving to dense scotoma
      compared with those with intact photoreceptor IS/OS junction (odds ratio 3.56,
      95% CI 2.41-5.27). CONCLUSIONS: Retinal sensitivity changes are correlated to IRL
      and ORL thickness changes, and to photoreceptor IS/OS junction integrity. FAF
      patterns remain a relevant factor in predicting GA evolution. Microperimetry, SW
      FAF and NIR-FAF, and SD-OCT should be combined to obtain adequate morphologic and
      functional prospective information.

PMID- 24093186
TI  - Fixation stability measurements in patients with neovascular age-related macular
      degeneration treated with ranibizumab.
AB  - OBJECTIVE: To evaluate which of 2 measuring units (bivariate contour ellipse area
      [BCEA] vs Fujii) yields more accurate measurements of fixation stability,
      obtained using the MP-1 device, in patients with neovascular age-related macular
      degeneration (nAMD) treated with intravitreal injections of ranibizumab, during a
      12-month follow-up period. DESIGN: Small retrospective, noncomparative,
      interventional case series. PARTICIPANTS: A total of 25 eyes in 25 patients (13
      males, 12 females; mean age 71.72 +/- 7.98 years). METHODS: All participants were
      older than 50 years, diagnosed with active subfoveal choroidal
      neovascularization, had best corrected visual acuity (BCVA) values above 20/100,
      and all lesion types were included. All patients underwent a loading phase with 3
      consecutive intravitreal injections of 0.05 mg ranibizumab at monthly intervals.
      Patients were retreated after the third injection if they exhibited a 100-MUm
      increase in macular thickness or evidence of intraretinal and/or subretinal fluid
      and new subretinal hemorrhage, observed with spectral-domain optical coherence
      tomography and fluorescein angiography. The data collected included BCVA and mean
      macular sensitivities, BCEA, and fixation patterns, performed at baseline and at
      months 4 and 12, using the MP-1 device. RESULTS: The mean total injection number
      was 5.92 +/- 1.18 (minimum 3, maximum 8). Mean BCVA at baseline was 0.55 +/- 0.28
      logMAR and increased significantly to 0.50 +/- 0.33 logMAR. Mean macular
      sensitivity at baseline was 7.06 +/- 4.59 dB and increased significantly to 8.40
      +/- 4.82. Mean BCEA was 2.19 +/- 1.38 deg(2) and decreased significantly to 1.68
      +/- 1.43 deg(2). Fixation stability patterns, according to the protocol set out
      by Fujii, did not change significantly during follow-up. CONCLUSIONS: Compared
      with Fujii fixation stability patterns, BCEA correlated better with variations in
      macular sensitivity and BCVA. BCEA can be added to the traditional parameters
      used to evaluate the efficacy of intravitreal injections in patients with nAMD.

PMID- 24093187
TI  - Use of microperimetry to evaluate hydroxychloroquine and chloroquine retinal
      toxicity.
AB  - OBJECTIVE: To check the ability of microperimetry to detect early retinal damage
      in patients with rheumatism taking hydroxychloroquine (HCQ), chloroquine (CQ), or
      both, and to describe the microperimetric alterations attributable to these drugs
      and their correlation with some clinical variables. DESIGN: Controlled cross
      sectional study. PARTICIPANTS: Patient group was 209 patients taking HCQ or CQ.
      Control group was 204 individuals not taking antimalarials. Exclusion criterion
      was other diseases that could alter microperimetry. METHODS: An ophthalmic
      examination and a microperimetry were performed on all individuals. Outcomes
      measured were average threshold, fixation stability, and macular integrity.
      Information about patient weight, height, main diagnosis, daily and cumulative
      dose, and creatinine, bilirubin, and transaminases levels were collected.
      Analysis of variance, t tests, and a regression analysis were carried out to
      detect differences between groups. RESULTS: Significant differences in
      microperimetry indexes were detected between cases and control subjects, between
      patients of different age groups, and between patients taking CQ and HCQ.
      Significant differences were also detected in retinal sensitivity between
      patients overdosed for CQ, but not for those overdosed for HCQ. Daily overdosing
      per ideal weight alone cannot explain retinal toxicity, although the effect of
      cumulative dose in macular sensibility is significant to explain both average
      threshold and macular integrity. CONCLUSIONS: Microperimetry is an accurate tool
      for detecting early macular hyposensibility caused by CQ and HCQ. Microperimetry
      indexes of retinal sensibility are worse in elderly patients taking these drugs
      and in short-stature patients taking CQ. A high cumulative dose is an important
      factor in explaining retinal hyposensibility on microperimetry.

PMID- 24093188
TI  - Efficacy of SLO-Microperimetry and Humphrey for evaluating macular sensitivity
      changes in advanced glaucoma.
AB  - OBJECTIVE: To compare the efficacy of scanning laser ophthalmoscope
      microperimetry (SLO-MP) and Humphrey visual fields in detecting macular
      sensitivity changes in advanced glaucoma. DESIGN: Prospective cohort study.
      PARTICIPANTS: 25 patients with advanced primary open angle glaucoma and 2
      consecutive abnormal Humphrey 10-2 SITA Standard visual field tests. METHODS:
      Thirty-six eyes of 25 patients with 2 consecutive abnormal Humphrey 10-2 SITA
      Standard (H10) visual fields were retested with a modified 10-2 SLO-MP within 3
      months of the last reliable H10. A standardized grid was used to mark the macula.
      Primary outcome was change in mean macular sensitivity (dB; H10 and SLO-MP) in
      relation to mean macular retinal nerve fibre layer (RNFL) thickness (um) by SLO-
      optical coherence tomography (SLO-OCT). Secondary outcome was comparison of
      reliability indices for both tests. Linear regression was used for analysis.
      RESULTS: Mean macular sensitivity was significantly lower in SLO-MP (9.33 +/-
      3.37 dB) than H10 (18.83 +/- 6.46 dB; p < 0.0001). Mean macular RNFL thickness
      correlated significantly with retinal sensitivity by both SLO-MP (r = 0.39, p <
      0.02) and H10 (r = 0.37, p < 0.03). Fixation losses were better controlled in SLO
      MP (0.38 +/- 1.1) than H10 (4.28 +/- 7.9; p = 0.008). False-positive responses
      were similar (SLO-MP: 2.25 +/- 4.53, H10: 1.78 +/- 3.33; p = 0.80). A
      statistically significant difference was noted in the false-negative responses
      (SLO-MP: 26.87 +/- 25.24, H10: 5.33 +/- 9.70; p < 0.0001). CONCLUSIONS: Macular
      sensitivity determined by both H10 and SLO-MP correlates significantly with mean
      macular RNFL thickness measured by SLO-OCT. Precise localization of the macula in
      SLO-MP results in lower fixation losses. Detection of denser field defects by SLO
      MP results in higher false-negative responses. A larger sample size is needed to
      further study the value of this diagnostic tool.

PMID- 24093189
TI  - Applicability of scanning laser ophthalmoscopy microperimetry on the fixation
      patterns of monofixation syndrome.
AB  - OBJECTIVE: To investigate the monocular fixation pattern and characteristics in
      patients with monofixation syndrome using scanning laser ophthalmoscopy (SLO)
      microperimetry (MP). METHODS: Twenty-four patients older than 5 years who had 8
      prism diopters (PD) or less of deviation after surgery were analyzed. The A group
      included 14 patients with infantile esotropia (ET), and 10 patients with acquired
      ET were assigned to B group. The monocular fixation pattern and characteristics
      of all patients were investigated using SLO MP. Central or mild eccentric
      fixation was defined as eyes with more than 50% of the fixation points located
      within the 2 degrees  diameter circle centred on the fovea. RESULTS: Mean ages at
      the time of surgery were 27 (range, 11-48) months in A group and 75 (range, 27
      166) months in B group. Mean ages at the time of MP examination were 117 (range,
      64-210) months in A group and 106 (range, 64-167) months in B group. Mean distant
      and near angles of esodeviation were -1.7 PD (-8 to 8) and -2.7 PD (-8 to 6) in A
      group and 0.6 PD (-2 to 8) and -0.4 PD (-2 to 0) in B group. Central or mild
      eccentric fixation was present in 8 patients (57%) and moderate or severe
      eccentric fixation in 6 patients (43%) in A group. In contrast, all patients in B
      group had central or mild eccentric fixation (p = 0.022). CONCLUSIONS:
      Postoperative moderate eccentric or severe eccentric fixations were observed in
      43% of patients with infantile ET in either eye; however, all patients with
      acquired ET showed central or mild eccentric fixation in both eyes.

PMID- 24093190
TI  - Rehabilitative approach in patients with ring scotoma.
AB  - OBJECTIVE: To investigate the rehabilitative approach in patients with ring
      scotoma. A central scotoma is characteristic for patients with age-related
      macular degeneration (AMD). Sometimes patients with AMD maintain a residual
      central vision area within the scotoma (ring scotoma). DESIGN: Prospective,
      nonrandomized case series. PARTICIPANTS: Twenty-four patients with AMD. METHODS:
      A formal low-vision assessment was performed for all study patients. The
      assessment included best corrected visual acuity (BCVA), contrast sensitivity,
      reading speed, and microperimetry. All patients were provided a low-vision
      assessment to satisfy patients' needs. Devices were prescribed accordingly.
      RESULTS: The BCVA found was 0.4 logMAR (SD 0.1). All had central and stable
      fixation. Residual central retinal area size and sensitivity measured 2.4 degrees
      (SD 0.8) and 3.1 dB (SD 0.8), respectively. Twenty patients achieved better
      vision with optical magnification in the eye with ring scotoma. Mean reading
      speed achieved was 50.2 words/min (SD 20.9). A linear correlation was found for
      reading speed with both central area sensitivity (r2 = 0.5, p < 0.05) and
      contrast sensitivity (r2 = 0.3, p < 0.05). CONCLUSIONS: In patients with AMD with
      ring scotoma, moderate amounts of magnification seem to provide satisfactory
      rehabilitation outcomes. Central retinal spared area sensitivity may predict
      reading speed outcomes, whereas residual central area size is likely to be useful
      in determining magnification.

PMID- 24093191
TI  - Use of prisms for vision rehabilitation after macular function loss may impact
      oculomotor control.
AB  - OBJECTIVE: To determine the effect from using prisms for image relocation on
      fixation stability estimates in low-vision (LV) patients with age-related macular
      degeneration (AMD). METHODS: The study was designed as a prospective,
      nonrandomized, observational case series. Inclusion criteria included documented
      AMD, LV with best corrected visual acuity of 20/50 to 20/400 in the better eye,
      and cases wearing distance glasses with prisms for image relocation incorporated
      in the glasses. Preferred retinal locus (PRL) and fixation stability were
      assessed using the Nidek MP1 and MAIA microperimeters. A control group was used
      to compare results. RESULTS: We recruited 14 study subjects with AMD and 10 with
      no retinal pathology serving as a control group. On average, 6 (SD 2) prisms
      diopters were prescribed to all in distant viewing glasses. Fixation stability
      was better at 3-month interval from baseline (p = 0.021) in the AMD group and
      stayed the same for the following 9 months. No change in fixation stability was
      noticed in the control group. There was no statistically significant difference
      in PRL eccentricity between the 3- and 12-month intervals in the AMD group (p =
      0.39). However, there was a positive correlation between PRL eccentricity and
      baseline bivariate contour ellipse area in the AMD group (p = 0.052).
      CONCLUSIONS: Patients with LV with AMD who are using prisms for image relocation
      toward the peripheral retinal exhibit better fixation stability than those who
      are not using prisms. Better fixation stability may impact on other visual
      outcomes. Use of prisms should be considered in any LV rehabilitation attempt and
      used in conjunction with other modern interventions in LV rehabilitation.

PMID- 24093192
TI  - Biofeedback stimulation in patients with age-related macular degeneration:
      comparison between 2 different methods.
AB  - OBJECTIVE: To evaluate changes in patient's visual performance after
      rehabilitation training with 2 different biofeedback training programs offered by
      the MP-1 microperimeter. Spontaneous retinal location of preferred retinal loci
      (PRLs) and fixation stability are not always optimal for best visual
      performances. MP-1 microperimeter biofeedback techniques have been suggested as
      modalities for training for better fixation stability and to find a better
      location of the new PRL in a more useful area of the retina in nonoptimal cases.
      The MP-1 microperimeter offers different biofeedback strategies, such as acoustic
      biofeedback and structured light stimulus plus acoustic biofeedback. DESIGN:
      Retrospective study. PARTICIPANTS: Thirty subjects affected by age-related
      macular degeneration with absolute central scotoma. METHODS: A standard protocol
      of examination before and after visual rehabilitation training was performed on
      all study subjects. Assessment included demographics data, visual acuity,
      fixation stability, retinal sensitivity, and reading speed. Rehabilitation
      training was performed with standard and structured stimulus biofeedback. The
      whole sample was divided into 2 groups of 15 patients attending the 2 different
      stimulation training biofeedback. RESULTS: Mean reading speed was found to be
      significantly increased for both groups (p < 0.05 and p < 0.01). Also, a
      statistically significant improvement of fixation stability was registered for
      both groups (p < 0.01). Only patients trained with the flickering pattern
      biofeedback stimulation increased retinal sensitivity (p < 0.01). CONCLUSIONS:
      Both regular biofeedback and flickering pattern biofeedback training seem to
      improve visual functions. More benefits seem to be accrued, however, with
      flickering pattern biofeedback training.

PMID- 24093193
TI  - Visual rehabilitation in patients with myopic maculopathy: our experience.
AB  - OBJECTIVE: To evaluate the efficacy of the MP-1 microperimeter (Nidek
      Technologies Srl, Padova, Italy) and Visual Pathfinder (LACE Inc) in improving
      visual function of patients with myopic maculopathy. DESIGN: Prospective,
      nonrandomized, interventional case series. PARTICIPANTS: Seventeen patients (34
      eyes) between 36 and 58 years of age with myopic maculopathy and central retinal
      scotomas. METHODS: After a complete eye examination, all patients underwent 10
      training sessions with MP-1 biofeedback (7 minutes) and Visual Pathfinder (3
      minutes) for each eye once a week. Statistical analysis was performed with
      Student t test. The p values less than 0.05 were considered statistically
      significant. RESULTS: The mean best corrected visual acuity increased from 0.64
      +/- 0.22 to 0.38 +/- 0.20 logMAR at the end of follow-up (p = 0.03); visual
      evoked potential P100 amplitude increased from 3.54 +/- 1.90 to 6.64 +/- 2.91 MUV
      at the end of follow-up (p = 0.04); average retinal sensitivity, calculated in
      the 12 degrees of the central retina, increased from 6.6 +/- 2.6 to 14.6 +/- 3.6
      dB (p = 0.03). Fixation behaviour in the 2 degrees of the central retina
      increased from 45% +/- 17% to 75% +/- 23% (p = 0.04). The bivariate contour
      ellipse area (95%) increased from 10.34 +/- 3.11 to 7.64 +/- 2.71 square degrees
      (p = 0.04). CONCLUSIONS: The combination of acoustic biofeedback training with MP
      1 and Visual Pathfinder offers a reasonable improvement of visual function in
      patients with myopic maculopathy. This method might be considered as a
      rehabilitative strategy as a "therapeutic option" in these patients for whom most
      treatments usually do not work.

PMID- 24093194
TI  - Maximum reading speed and binocular summation in patients with central vision
      loss.
AB  - OBJECTIVE: Visual acuity is a poor predictor of the maximum reading speed of
      patients with central vision loss. This study examines the effects of binocular
      summation of acuity on the maximum reading speed of these patients. DESIGN:
      Prospective, observational case series. PARTICIPANTS: Twenty patients with
      central vision loss participated. METHODS: Maximum reading speed was measured
      binocularly using the MNREAD acuity charts. Monocular and binocular acuities were
      measured with the Early Treatment Diabetic Retinopathy Study (ETDRS) chart.
      Binocular summation was evaluated with a binocular ratio (BR) calculated as the
      ratio between the acuity of the better eye to binocular acuity. Fixation
      stability and preferred retinal locus (PRL) distance from the former fovea were
      evaluated with the MP-1 microperimetre. RESULTS: Six patients experienced acuity
      summation (BR > 1.05), 5 experienced acuity inhibition (BR < 0.95), and 9 showed
      equality (BR = 1 +/- 0.05). There were no differences in the mean acuity of the
      better eye, fixation stability, or PRL distance from the fovea of the 3 groups.
      Maximum reading speed was significantly slower (p < 0.05) for patients who
      experienced binocular inhibition (mean 42 +/- 27 words/min [wpm], median 40 wpm)
      than for those who experienced binocular summation (mean 107 +/- 39 wpm, median
      108 wpm) or equality (mean 111 +/- 62 wpm, median 90 wpm). BR correlated with the
      maximum reading speed for the overall sample (r[18] = 0.49, p = 0.03). BR
      together with PRL distance from the former fovea in the better eye explained 45%
      of the variance in maximum reading speed. CONCLUSIONS: Binocular summation of
      acuity rather than visual acuity alone affects maximum reading speed of patients
      with central vision loss. Patients with binocular inhibition read significantly
      slower than those with binocular summation or equality. Assessment of binocular
      summation is important when devising reading rehabilitation techniques.

PMID- 24093195
TI  - Microperimetry in a case of occult macular dystrophy.

PMID- 24093196
TI  - Utility of microperimetry in nystagmus: a case report.

PMID- 24093197
TI  - Microperimetric biofeedback in a patient with oculocutaneous albinism.

PMID- 24093199
TI  - Visual function and risk genotypes in maternally inherited diabetes and deafness.

PMID- 24093200
TI  - Multiple evanescent white dot syndrome following recent influenza vaccination.

PMID- 24093198
TI  - Rehabilitation with MP1 biofeedback training of a posterior microphthalmos case.

PMID- 24093201
TI  - Paraneoplastic optic neuropathy and retinopathy associated with colon
      adenocarcinoma.

PMID- 24093202
TI  - Pallid disc edema and choroidal perfusion delay in posthemodialysis nonarteritic
      ischemic optic neuropathy.

PMID- 24093204
TI  - Corneal nerve regeneration after foreign body removal on in vivo confocal
      microscopy.

PMID- 24093205
TI  - Tuberculous dacryoadenitis unveils HIV infection.

PMID- 24093206
TI  - Comparing EPI-743 treatment in siblings with Leber's hereditary optic neuropathy
      mt14484 mutation.

PMID- 24093203
TI  - Atonic pupils secondary to presumed systemic vasopressor-related ischemia.

PMID- 24093207
TI  - Office-based needle aspiration of idiopathic acute subperiosteal hematoma.

PMID- 24093208
TI  - Ophthalmic cell-phone imaging system: a costless imaging system.

PMID- 24093209
TI  - Everyday use of modern microperimetry in a low-vision service.

PMID- 24093211
TI  - High prevalence of interatrial septal aneurysm in young adults who were born
      preterm.
AB  - BACKGROUND: The cardiovascular vulnerability of young adults who were born
      preterm was first acknowledged over a decade ago. AIMS: (1) To examine the
      echocardiographic characteristics of a group of young adults born preterm with an
      extremely low birthweight (<1000 g; ex-ELBW) in comparison with healthy controls
      born at term (C); (2) to identify a correlation between the potential
      echocardiographic abnormalities detected in ex-ELBW and their anthropometric
      parameters, age, presence of respiratory distress, patency of ductus arteriosus,
      length of stay in Neonatal Intensive Care Unit. METHODS: Thirty-seven ex-ELBW (11
      males, 26 females; mean age: 22.2 +/- 1.8 years) were compared with 37 C (11
      males, 26 females). Both groups underwent standard mono- and bi-dimensional
      transthoracic echocardiogram with color Doppler. RESULTS: No statistically
      significant differences were detected between the two groups regarding mono
      dimensional echocardiography or Doppler measurements (p = ns). Conversely, a
      statistically significant difference was observed between the prevalence of
      interatrial septal aneurysm (ASA) in ex-ELBW compared to C (p = 0.0016). A
      significant association was likewise observed between ASA and the presence of
      both respiratory distress at birth (p < 0.05) and patency of the ductus
      arteriosus (p < 0.05). CONCLUSIONS: A significant prevalence of ASA was detected
      in ex-ELBW subjects compared to C, underlining a probable correlation with
      respiratory distress and patent ductus arteriosus. In view of the association
      between ASA and stroke in young adults devoid of other cerebrovascular risk
      factors, this unexpected observation suggests that all ex-preterm subjects should
      undergo transthoracic or transesophageal echocardiographic examination with the
      aim of detecting this potentially emboligenic cardiac abnormality.

PMID- 24093210
TI  - The repetitive component of the sunflower genome as shown by different procedures
      for assembling next generation sequencing reads.
AB  - BACKGROUND: Next generation sequencing provides a powerful tool to study genome
      structure in species whose genomes are far from being completely sequenced. In
      this work we describe and compare different computational approaches to evaluate
      the repetitive component of the genome of sunflower, by using medium/low coverage
      Illumina or 454 libraries. RESULTS: By varying sequencing technology (Illumina or
      454), coverage (0.55 x-1.25 x), assemblers and assembly procedures, six different
      genomic databases were produced. The annotation of these databases showed that
      they were composed of different proportions of repetitive DNA families. The final
      assembly of the sequences belonging to the six databases produced a whole genome
      set of 283,800 contigs. The redundancy of each contig was estimated by mapping
      the whole genome set with a large Illumina read set and measuring the number of
      matched Illumina reads. The repetitive component amounted to 81% of the sunflower
      genome, that is composed mainly of numerous families of Gypsy and Copia
      retrotransposons. Also many families of non autonomous retrotransposons and DNA
      transposons (especially of the Helitron superfamily) were identified.
      CONCLUSIONS: The results substantially matched those previously obtained by using
      a Sanger-sequenced shotgun library and a standard 454 whole-genome-shotgun
      approach, indicating the reliability of the proposed procedures also for other
      species. The repetitive sequences were collected to produce a database, SUNREP,
      that will be useful for the annotation of the sunflower genome sequence and for
      studying the genome evolution in dicotyledons.

PMID- 24093212
TI  - Pure retroperitoneal laparoscopic radical nephrectomy for left renal cell
      carcinoma with differential extensions of level I renal vein tumor thrombus.
AB  - OBJECTIVES: To describe a large clinical series of pure laparoscopic radical
      nephrectomy (LRN) for left renal cell carcinoma (RCC) with differential
      extensions of level I renal vein (RV) tumor thrombus using a retroperitoneal
      approach. METHODS: Ten left RCC patients with RV tumor thrombus underwent pure
      retroperitoneal LRN. Operation procedures were different for patients with
      varying length of the RV tumor thrombus. Based on our experience, four grades
      were defined based on the distal limit of the thrombus. Grade 1: tip of the
      thrombus was located between the renal sinus and the left gonadal vein (or
      adrenal vein); Grade 2: tip of the thrombus was located between the left gonadal
      vein and the abdominal aorta; Grade 3: tip of the thrombus was riding on the
      abdominal aorta; Grade 4: tip of the thrombus was located in the interaortocaval
      region. According to this classification, grade 1 in 3 patients, grade 2 in 2,
      grade 3 in 3, and grade 4 in 2. RESULTS: Pure retroperitoneal LRN and
      thrombectomy were successfully performed for all the patients without requiring
      open surgery. The mean tumor size for each of the four grades was 5.9, 6.4, 5.8,
      and 7.6 cm, respectively; the mean thrombus length was 2.1, 3.5, 5.2, and 7.1 cm,
      respectively; the mean operative time was 85, 103, 137, and 190 minutes,
      respectively; the average surgical bleeding volume was 67, 110, 143, and 225 mL,
      respectively. Better procedures are needed to increase the working space for
      patients with higher grades of thrombus. Surgical margins were negative for all
      patients. With a mean follow-up of 29 months, two patients developed metastatic
      disease. CONCLUSIONS: Despite the technical challenges, pure retroperitoneal LRN
      for left RCC patients with differential extensions of RV tumor thrombus is safe
      and feasible in selected patients. However, it is important to note that surgery
      will be more difficult for patients with higher grades of thrombus.

PMID- 24093213
TI  - A phase I, dose-escalation study of cyclical weekly oral temozolomide and weekly
      PEG-interferon alpha-2b in patients with refractory or advanced solid tumours.
AB  - BACKGROUND: Temozolomide (TMZ) is an oral alkylating agent used in the treatment
      of central nervous system neoplasms and metastatic melanoma. Preclinical and
      clinical data suggested that combining TMZ with interferon alpha-2b (IFN-alpha
      2b) may result in increased anti-tumour efficacy. METHODS: This was a phase I,
      dose-escalation study to define the maximum tolerated dose (MTD) and dose
      limiting toxicities (DLT) of cyclical oral TMZ (days 1-7 and 15-21) in
      combination with pegylated IFN-alpha-2b (PEG-IFN-alpha-2b) in patients with
      advanced solid tumours. RESULTS: We treated 19 patients (10 female and nine
      male), median age 58 years (range: 41-79 years). Ten patients tolerated TMZ at
      100 mg/m2 on days 1-7 and 15-21 plus PEG-IFN-alpha-2b at 1.5 mcg/kg/week on 28
      day cycles which was the MTD of the combination. The pharmacokinetic parameters
      of PEG-IFN-alpha-2b were not altered by TMZ, at the MTD. CONCLUSION: The MTD of
      cyclical oral TMZ was 100 mg/m2 on days 1-7 and 15-21 when combined with weekly
      subcutaneous PEG-IFNalpha-2b at 1.5 mcg/kg/week on 28 days cycles. The PK of PEG
      IFN-alpha-2b appeared consistent with those when it is used as monotherapy.

PMID- 24093215
TI  - Gender-specific influence of socioeconomic status on the prevalence of migraine
      and tension-type headache: the results from the Korean Headache Survey.
AB  - BACKGROUND: Socioeconomic status plays an important role in pain coping strategy.
      Its influence on migraine and tension-type headache may differ by gender. This
      study aimed to evaluate how socioeconomic status affects the prevalence of
      migraine and tension-type headache by gender. METHODS: We used data from the
      Korean Headache Survey, a population-based sample of Koreans aged 19-69 years.
      Education level, district size, and household income were evaluated as
      socioeconomic variables. RESULTS: Among 1507 participants, the 1-year prevalence
      rates of migraine and tension-type headache were 8.7% [95% confidence interval
      (CI) 1.9-4.6%] and 29.1% (95% CI 25.7-32.5%) in women and 3.2% (95% CI 1.9-4.6%)
      and 32.5% (95% CI 29.1-35.9%) in men, respectively. In women, multiple regression
      analysis found that living in rural areas was related to higher prevalence of
      migraine [odds ratio (OR) 4.52, 95% CI 1.85-11.02] and lower prevalence of
      tension-type headache (OR 0.29, 95% CI 0.15-0.58) and college-level education was
      related to lower prevalence of tension-type headache (OR 0.37, 95% CI 0.18-0.74).
      In men, multiple regression analysis failed to reveal significant influences of
      any socioeconomic variable on the prevalence of migraine or tension-type
      headache. CONCLUSIONS: The influence of socioeconomic status on migraine and
      tension-type headache differs by gender, with women being more susceptible to
      socioeconomic influence.

PMID- 24093214
TI  - Suicide and related health risk behaviours among school learners in South Africa:
      results from the 2002 and 2008 national youth risk behaviour surveys.
AB  - BACKGROUND: Attempted and completed suicide constitute a major public health
      problem among young people world-wide, including South Africa (SA). Suicide
      attempt and completed suicide increase during the adolescent period. One in 5
      adolescents considers attempting suicide, but statistics are frequently
      unreliable. METHODS: Data for this study were derived from the 2002 and 2008
      South African Youth Risk Behaviour Surveys (YRBS). The study population comprised
      grades 8, 9, 10 and 11 students in governmental schools in the nine provinces of
      SA (N = 10,699 in 2002 and 10,270 in 2008). Key outcome measures were suicide
      ideation and suicide attempts. RESULTS: Of the total sample, 18% of the students
      in 2002 and 19% in 2008 reported to have seriously considered and/or made a plan
      to commit suicide during the past six months (Suicide ideation), whereas 18.5% of
      students in 2002 and 21.8% in 2008 reported that they had attempted suicide at
      least 1 time during the past six months. On both suicide measures girls have
      higher prevalence scores than boys, and older school learners score higher than
      younger learners. In addition, 32% of the learners reported feelings of sadness
      or hopelessness. These feelings contributed significantly to the explanation of
      suicide ideation and suicide attempt next to being the victim or actor in violent
      acts and illegal substance use. CONCLUSION: The prevalence of suicide ideation
      and suicide attempts among South African adolescents is high and seems to be
      influenced by a wide spectrum of factors at the demographic, psychological and
      behavioural level. Hence, more research is needed to determine the behavioural
      and psychological determinants of suicide among youngsters in order to develop
      comprehensive intervention strategies for suicide prevention and care.

PMID- 24093217
TI  - Collet-Sicard syndrome: a rare cause of hypoglossal nerve palsy.

PMID- 24093216
TI  - Mental health research and evaluation in multicultural Australia: developing a
      culture of inclusion.
AB  - INTRODUCTION: Cultural and linguistic diversity is a core feature of the
      Australian population and a valued element of national identity. The proportion
      of the population that will be overseas-born is projected to be 32% by 2050.
      While a very active process of mental health system reform has been occurring for
      more than two decades - at national and state and territory levels - the
      challenges presented by cultural and linguistic diversity have not been
      effectively met. A key area in which this is particularly an issue is in the
      collection, analysis and reporting of mental health data that reflect the reality
      of population diversity. The purpose of this study was to examine: what is known
      about the mental health of immigrant and refugee communities in Australia;
      whether Australian mental health research pays adequate attention to the fact of
      cultural and linguistic diversity in the Australian population; and whether
      national mental health data collections support evidence-informed mental health
      policy and practice and mental health reform in multicultural Australia. METHODS:
      The study consisted of three components - a brief review of what is known about
      mental health in, and mental health service use by, immigrant and refugee
      communities; an examination of national data collections to determine the extent
      to which relevant cultural variables are included in the collections; and an
      examination of Australian research to determine the extent to which immigrant and
      refugee communities are included as participants in such research. RESULTS: The
      review of Australian research on mental health of immigrant and refugee
      communities and their patterns of mental health service use generated findings
      that are highly variable. The work is fragmented and usually small-scale. There
      are multiple studies of some immigrant and refugee communities and there are no
      studies of others. Although there is a broadly consistent pattern of lower rates
      of utilisation of specialist public mental health services by immigrants and
      refugees the absence of adequate population epidemiological data prevents
      judgments about whether the observed patterns constitute under-utilisation. There
      are virtually no data on quality of service outcomes. The examination of national
      data collections revealed multiple gaps in these data collections. The review of
      papers published in four key Australian journals to determine whether immigrants
      and refugees are included in mental health research studies revealed a high rate
      (9.1%) of specific exclusion from studies (usually due to low English fluency)
      and a much higher rate of general neglect of the issue of population diversity in
      study design and reporting. CONCLUSIONS: While there are many positive statements
      of policy intent in relation to immigrant and refugee communities in national
      mental health policies and strategies there is virtually no reporting by
      Commonwealth or State and Territory governments of whether policies that are
      relevant to immigrant and refugee communities are effectively implemented. It is
      not possible, on the basis of the data collected, to determine whether immigrant
      and refugee communities are benefiting from the mental health system reforms that
      are being actively carried out. The majority of Australian mental health research
      does not adequately include immigrant and refugee samples. On the basis of the
      findings of this study eight strategies have been recommended that will
      contribute to the development of a culture of inclusion of all Australians in the
      national mental health research enterprise.

PMID- 24093218
TI  - Effects of vitamin D receptor polymorphisms on urolithiasis risk: a meta
      analysis.
AB  - BACKGROUND: Several studies analyzed the associations of Vitamin D receptor (VDR)
      polymorphisms with urolithiasis risk in different ethnic groups. However, the
      results were inconclusive. To evaluate a more precise estimation of the
      relationship, a meta-analysis was performed. METHODS: Pubmed, EMBASE, Wanfang
      Database, China National Knowledge Infrastructure (CNKI) and Weipu Database were
      searched. Data were extracted independently by two investigators. Odds ratios
      (ORs) with 95% confidence intervals (CIs) were used to assess the strength of
      associations. RESULTS: Twenty-three case-control studies were included in this
      meta-analysis. Significant associations between ApaI, BsmI, FokI, and TaqI
      polymorphisms and urolithiasis risk were observed. However, sensitivity analyses
      for BsmI and FokI polymorphisms indicated that the results were not reliable and
      credible. In addition, there was a significant association of the ApaI-TaqI
      haplotype with urolithiasis risk. CONCLUSIONS: This meta-analysis suggested that
      ApaI and TaqI polymorphisms in VDR gene were associated with urolithiasis risk.

PMID- 24093219
TI  - Assessing health workers' revenues and coping strategies in Nigeria--a mixed
      methods study.
AB  - BACKGROUND: The setting of realistic performance-based financing rewards
      necessitates not just knowledge of health workers' salaries, but of the revenue
      that accrues from their additional income-generating activities. This study
      examined the coping mechanisms of health workers in the public health sector of
      Nasarawa and Ondo states in Nigeria to supplement their salaries and benefits; it
      also estimated the proportionate value of the revenues from those coping
      mechanisms in relation to the health workers' official incomes. METHODS: This
      study adopted a mixed-methods approach, consisting of semi-structured interviews,
      a review of policy documents, a survey using self-administered questionnaires,
      and the randomized response technique (RRT). In all, 170 health workers (86 in
      Ondo, 84 in Nasarawa) participated in the survey. In-depth interviews were
      conducted with 24 health workers (12 per state) and nine policy makers from both
      states. RESULTS: The health workers perceived their salaries as inadequate,
      though most policy makers differed in this assessment. There appeared to be a
      considerable expenditure-income disparity among the respondents. Approximately
      56% (n = 93) of the study population reported having additional earning
      arrangements: most reported non-medical activities such as farming and trading,
      but private practice was also frequently reported.Half of the respondents with
      additional earning arrangements stated that their income from those activities
      was the equivalent of half or more of their monthly salaries. Specifically, 35%
      (n = 32) said that they earned about half of their official monthly salaries and
      15% (n = 14) reported earning the same or more than their monthly salaries from
      these activities. Other coping mechanisms used by the health workers included
      prioritizing activities that enabled the earning of per diems, collecting
      informal payments and gifts from patients, and pilfering drugs from facilities.
      CONCLUSIONS: Predatory and non-predatory mechanisms accounted for the health
      workers' additional income. It may be difficult for the health workers to meet
      their expenses with their salaries and financial incentives; this highlights the
      need for the regulation of additional earnings and to implement targeted
      accountability mechanisms. This study indicates the value of using mixed methods
      when investigating sensitive issues. Future studies of this type should employ
      mixed methods for triangulation purposes to provide better insight into health
      workers' responses.

PMID- 24093220
TI  - Development and implementation of mass media campaigns to delay sexual initiation
      among African American and White youth.
AB  - Reducing new HIV/STD infections among at-risk adolescents requires developing and
      evaluating evidence-based health communication approaches. Research
      overwhelmingly supports the conclusion that early sexual initiation is associated
      with STDs and other negative outcomes in later years (e.g., unintended
      pregnancy). The authors' research group secured funding from the National
      Institute of Mental Health to develop, implement, and rigorously evaluate
      televised mass media campaigns to delay initiation of sexual intercourse among
      African American and White adolescents in two cities in the Southeastern United
      States. The focus of the present study is on the development and implementation
      of the campaigns, including (a) rationale and theoretical underpinnings; (b)
      collection, screening, and assessment of existing public service announcements;
      (c) development of new public service announcements; (d) study design and
      campaign airing plan; and (e) message exposure achieved in the campaigns. Health
      communication campaigns hold much promise in reaching at-risk adolescent
      populations with targeted, timely, and relevant risk-reduction messages. 

PMID- 24093222
TI  - A retrospective study on IVF/ICSI outcome in patients with anti-nuclear
      antibodies: the effects of prednisone plus low-dose aspirin adjuvant treatment.
AB  - BACKGROUND: Anti-nuclear antibodies (ANA) are suspected of having relevance to
      adverse reproductive events. METHODS: This study aims to investigate the
      potential effect of ANA on IVF/ICSI outcome and the therapeutic role of
      prednisone plus low-dose aspirin (P + A) adjuvant treatment in ANA + patients.
      The first IVF/ICSI cycles without P + A of sixty-six ANA + women were enrolled as
      the ANA + group, and the 233 first IVF/ICSI cycles of matched ANA- women served
      as the ANA- group. The ANA + group was divided into the Titre < =1:320 subgroup
      and the Titre > 1:320 subgroup. Twenty-one ANA + women with adverse outcomes in
      their first cycles (ANA + cycles without P + A) received P + A adjuvant treatment
      for three months before the second IVF/ICSI cycle (ANA + cycles with P + A). The
      clinical characteristics and the IVF/ICSI outcomes were compared, respectively,
      between 1) the ANA + group and the ANA- group, 2) the Titre < =1:320 subgroup and
      the Titre > 1:320 subgroup, and 3) the ANA + cycles without P + A and the ANA +
      cycles with P + A. RESULTS: No significant differences were observed between each
      of the two-group pairs in the clinical characteristics. The ANA + group exhibited
      significantly lower MII oocytes rate, normal fertilisation, pregnancy and
      implantation rates, as well as remarkably higher abnormal fertilisation and early
      miscarriage rates. The Titre < =1:320 subgroup's IVF/ICSI outcomes were as poor
      as those of the Titre > 1:320 subgroup. After the P + A adjuvant treatment, the
      number of two pro-nuclei, perfect embryos and available embryos, and the
      implantation rate increased significantly. CONCLUSIONS: These observations
      suggest that ANA could exert a detrimental effect on IVF/ICSI outcome that might
      not be titre-dependent, and P + A adjuvant treatment could be useful for ANA +
      patients. This hypothesis should be verified in further prospective randomised
      studies.

PMID- 24093223
TI  - The effect of histological chorioamnionitis on the short-term outcome of preterm
      infants <=32 weeks: a single-center study.
AB  - BACKGROUND AND OBJECTIVES: Chorioamnionitis (CA) is an acute inflammation of the
      membranes and chorion of the placenta. The aim of this study was to determine the
      effect of histological CA on the short-term outcome of preterm infants. SUBJECTS
      AND METHODS: The clinical characteristics and outcomes of the preterm infant
      including respiratory distress syndrome, duration of mechanical ventilation,
      patent ductus arteriosus (PDA) requiring medical treatment or ligation,
      necrotizing enterocolitis, bronchopulmonary dysplasia, death and intraventricular
      hemorrhage (IVH; grade III-IV) were analyzed. RESULTS: Two hundred and eighty-one
      infants born at <=32 weeks gestational ages were included. Infants were divided
      into two groups: one with histological CA (n = 145) and without histological CA
      (n = 136). Mean gestational age was 28.8 +/- 2.6 weeks and 29.1 +/- 2.5 weeks,
      and mean birth weight was 1138 +/- 350 g and 1210 +/- 299 g, respectively. There
      were no differences in gestational age and birth weight among the groups.
      Compared with the group, histological CA was associated with early onset sepsis
      (p = 0.007), PDA (p = 0.003), IVH (p = 0.03), and death (p = 0.04). CONCLUSION:
      Maternal histological CA is an important risk factor for preterm deliveries and
      associated with serious morbidities such as early onset sepsis, IVH, PDA and
      increased mortality.

PMID- 24093224
TI  - Genome-wide transcriptional analysis of two soybean genotypes under dehydration
      and rehydration conditions.
AB  - BACKGROUND: Soybean is an important crop that provides valuable proteins and oils
      for human use. Because soybean growth and development is extremely sensitive to
      water deficit, quality and crop yields are severely impacted by drought stress.
      In the face of limited water resources, drought-responsive genes are therefore of
      interest. Identification and analysis of dehydration- and rehydration-inducible
      differentially expressed genes (DEGs) would not only aid elucidation of molecular
      mechanisms of stress response, but also enable improvement of crop stress
      tolerance via gene transfer. Using Digital Gene Expression Tag profiling (DGE), a
      new technique based on Illumina sequencing, we analyzed expression profiles
      between two soybean genotypes to identify drought-responsive genes. RESULTS: Two
      soybean genotypes - drought-tolerant Jindou21 and drought-sensitive Zhongdou33 -
      were subjected to dehydration and rehydration conditions. For analysis of DEGs
      under dehydration conditions, 20 cDNA libraries were generated from roots and
      leaves at two different time points under well-watered and dehydration
      conditions. We also generated eight libraries for analysis under rehydration
      conditions. Sequencing of the 28 libraries produced 25,000-33,000 unambiguous
      tags, which were mapped to reference sequences for annotation of expressed genes.
      Many genes exhibited significant expression differences among the libraries. DEGs
      in the drought-tolerant genotype were identified by comparison of DEGs among
      treatments and genotypes. In Jindou21, 518 and 614 genes were differentially
      expressed under dehydration in leaves and roots, respectively, with 24 identified
      both in leaves and roots. The main functional categories enriched in these DEGs
      were metabolic process, response to stresses, plant hormone signal transduction,
      protein processing, and plant-pathogen interaction pathway; the associated genes
      primarily encoded transcription factors, protein kinases, and other regulatory
      proteins. The seven most significantly expressed (|log2 ratio| >= 8) genes -
      Glyma15g03920, Glyma05g02470, Glyma15g15010, Glyma05g09070, Glyma06g35630,
      Glyma08g12590, and Glyma11g16000 - are more likely to determine drought stress
      tolerance. The expression patterns of eight randomly-selected genes were
      confirmed by quantitative RT-PCR; the results of QRT-PCR analysis agreed with
      transcriptional profile data for 96 out of 128 (75%) data points. CONCLUSIONS:
      Many soybean genes were differentially expressed between drought-tolerant and
      drought-sensitive genotypes. Based on GO functional annotation and pathway
      enrichment analysis, some of these genes encoded transcription factors, protein
      kinases, and other regulatory proteins. The seven most significant DEGs are
      candidates for improving soybean drought tolerance. These findings will be
      helpful for analysis and elucidation of molecular mechanisms of drought
      tolerance; they also provide a basis for cultivating new varieties of drought
      tolerant soybean.

PMID- 24093226
TI  - Research in Computational Molecular Biology (RECOMB 2013).

PMID- 24093225
TI  - Clinical review: the critical care management of the burn patient.
AB  - Between 4 and 22% of burn patients presenting to the emergency department are
      admitted to critical care. Burn injury is characterised by a hypermetabolic
      response with physiologic, catabolic and immune effects. Burn care has seen
      renewed interest in colloid resuscitation, a change in transfusion practice and
      the development of anti-catabolic therapies. A literature search was conducted
      with priority given to review articles, meta-analyses and well-designed large
      trials; paediatric studies were included where adult studies were lacking with
      the aim to review the advances in adult intensive care burn management and place
      them in the general context of day-to-day practical burn management. 

PMID- 24093228
TI  - Detecting protein conformational changes in interactions via scaling known
      structures.
AB  - Conformational changes frequently occur when proteins interact with other
      proteins. How to detect such changes in silico is a major problem. Existing
      methods for docking with conformational changes remain time-consuming, and they
      solve only a small portion of protein complexes accurately. This work presents a
      more accurate method (FlexDoBi) for docking with conformational changes. FlexDoBi
      generates the possible conformational changes of the interface residues that
      transform the proteins from their unbound states to bound states. Based on the
      generated conformational changes, multidimensional scaling is performed to
      construct candidates for the bound structure. We develop a new energy item for
      determining the orientation of docking subunits and selecting of plausible
      conformational changes. Experimental results illustrate that FlexDoBi achieves
      better results. On 20 complexes, we obtained an average iRMSD of 1.55A, which
      compares favorably with the average iRMSD of 1.94A for FiberDock. Compared to
      ZDOCK, our results are of 0.27A less in average iRMSD of the medium difficulty
      group.

PMID- 24093227
TI  - Assembling single-cell genomes and mini-metagenomes from chimeric MDA products.
AB  - Recent advances in single-cell genomics provide an alternative to largely gene
      centric metagenomics studies, enabling whole-genome sequencing of uncultivated
      bacteria. However, single-cell assembly projects are challenging due to (i) the
      highly nonuniform read coverage and (ii) a greatly elevated number of chimeric
      reads and read pairs. While recently developed single-cell assemblers have
      addressed the former challenge, methods for assembling highly chimeric reads
      remain poorly explored. We present algorithms for identifying chimeric edges and
      resolving complex bulges in de Bruijn graphs, which significantly improve single
      cell assemblies. We further describe applications of the single-cell assembler
      SPAdes to a new approach for capturing and sequencing "microbial dark matter"
      that forms small pools of randomly selected single cells (called a mini
      metagenome) and further sequences all genomes from the mini-metagenome at once.
      On single-cell bacterial datasets, SPAdes improves on the recently developed E+V
      SC and IDBA-UD assemblers specifically designed for single-cell sequencing. For
      standard (cultivated monostrain) datasets, SPAdes also improves on A5, ABySS,
      CLC, EULER-SR, Ray, SOAPdenovo, and Velvet. Thus, recently developed single-cell
      assemblers not only enable single-cell sequencing, but also improve on
      conventional assemblers on their own turf. SPAdes is available for free online
      download under a GPLv2 license.

PMID- 24093229
TI  - IPED: inheritance path-based pedigree reconstruction algorithm using genotype
      data.
AB  - The problem of inference of family trees, or pedigree reconstruction, for a group
      of individuals is a fundamental problem in genetics. Various methods have been
      proposed to automate the process of pedigree reconstruction given the genotypes
      or haplotypes of a set of individuals. Current methods, unfortunately, are very
      time-consuming and inaccurate for complicated pedigrees, such as pedigrees with
      inbreeding. In this work, we propose an efficient algorithm that is able to
      reconstruct large pedigrees with reasonable accuracy. Our algorithm reconstructs
      the pedigrees generation by generation, backward in time from the extant
      generation. We predict the relationships between individuals in the same
      generation using an inheritance path-based approach implemented with an efficient
      dynamic programming algorithm. Experiments show that our algorithm runs in linear
      time with respect to the number of reconstructed generations, and therefore, it
      can reconstruct pedigrees that have a large number of generations. Indeed it is
      the first practical method for reconstruction of large pedigrees from genotype
      data.

PMID- 24093230
TI  - An algorithm for constructing parsimonious hybridization networks with multiple
      phylogenetic trees.
AB  - A phylogenetic network is a model for reticulate evolution. A hybridization
      network is one type of phylogenetic network for a set of discordant gene trees
      and "displays" each gene tree. A central computational problem on hybridization
      networks is: given a set of gene trees, reconstruct the minimum (i.e., most
      parsimonious) hybridization network that displays each given gene tree. This
      problem is known to be NP-hard, and existing approaches for this problem are
      either heuristics or making simplifying assumptions (e.g., work with only two
      input trees or assume some topological properties). In this article, we develop
      an exact algorithm (called PIRNC) for inferring the minimum hybridization
      networks from multiple gene trees. The PIRNC algorithm does not rely on
      structural assumptions (e.g., the so-called galled networks). To the best of our
      knowledge, PIRNC is the first exact algorithm implemented for this formulation.
      When the number of reticulation events is relatively small (say, four or fewer),
      PIRNC runs reasonably efficient even for moderately large datasets. For building
      more complex networks, we also develop a heuristic version of PIRNC called
      PIRNCH. Simulation shows that PIRNCH usually produces networks with fewer
      reticulation events than those by an existing method. PIRNC and PIRNCH have been
      implemented as part of the software package called PIRN and is available online.

PMID- 24093232
TI  - Noisy metrology beyond the standard quantum limit.
AB  - Parameter estimation is of fundamental importance in areas from atomic
      spectroscopy and atomic clocks to gravitational wave detection. Entangled probes
      provide a significant precision gain over classical strategies in the absence of
      noise. However, recent results seem to indicate that any small amount of
      realistic noise restricts the advantage of quantum strategies to an improvement
      by at most a multiplicative constant. Here, we identify a relevant scenario in
      which one can overcome this restriction and attain superclassical precision
      scaling even in the presence of uncorrelated noise. We show that precision can be
      significantly enhanced when the noise is concentrated along some spatial
      direction, while the Hamiltonian governing the evolution which depends on the
      parameter to be estimated can be engineered to point along a different direction.
      In the case of perpendicular orientation, we find superclassical scaling and
      identify a state which achieves the optimum. 

PMID- 24093233
TI  - Detecting topological phases in cold atoms.
AB  - Chern insulators are band insulators which exhibit a gap in the bulk and gapless
      excitations in the edge. Detection of Chern insulators is a serious challenge in
      cold atoms since the Hall transport measurements are technically unrealistic for
      neutral atoms. By establishing a natural correspondence between the time-reversal
      invariant topological insulator and the quantum anomalous Hall system, we show
      for a class of Chern insulators that the topology can be determined by only
      measuring Bloch eigenstates at highly symmetric points of the Brillouin zone.
      Furthermore, we introduce two experimental schemes, including the spin-resolved
      Bloch oscillation, to carry out the measurement. These schemes are highly
      feasible under realistic experimental conditions. Our results may provide a
      powerful tool to detect topological phases in cold atoms. 

PMID- 24093234
TI  - Cross-validated tomography.
AB  - We show that the information collected in the course of a generic quantum
      tomography experiment can be used for verifying experimenters' assumptions about
      the state preparation and measurement. In particular, systematic errors, such as
      drifts and instabilities inherent in the tomography setup, can be identified
      without the need for any specific measurements designed to detect such problems.
      This is done by statistical analysis of available tomography data. As an example,
      we discuss the detection and characterization of unexpected changes in the signal
      state preparation during the tomography measurement and argue that minimal
      tomography schemes, such as symmetric informationally complete measurements, are
      more difficult to validate than overcomplete schemes. The method is illustrated
      with the analysis of experimental quantum homodyne tomography. 

PMID- 24093235
TI  - Hardware-efficient autonomous quantum memory protection.
AB  - We propose to encode a quantum bit of information in a superposition of coherent
      states of an oscillator, with four different phases. Our encoding in a single
      cavity mode, together with a protection protocol, significantly reduces the error
      rate due to photon loss. This protection is ensured by an efficient quantum error
      correction scheme employing the nonlinearity provided by a single physical qubit
      coupled to the cavity. We describe in detail how to implement these operations in
      a circuit quantum electrodynamics system. This proposal directly addresses the
      task of building a hardware-efficient quantum memory and can lead to important
      shortcuts in quantum computing architectures. 

PMID- 24093236
TI  - Mapping spin coherence of a single rare-earth ion in a crystal onto a single
      photon polarization state.
AB  - We report on optical detection of a single photostable Ce(3+) ion in an yttrium
      aluminium garnet (YAG) crystal and on its magneto-optical properties at room
      temperature. The spin quantum state of the emitting level of a single cerium ion
      in YAG can be initialized by a circularly polarized laser pulse. Coherent
      precession of the electron spin is read out by observing temporal behavior of
      circularly polarized fluorescence of the ion. This implies direct mapping of the
      spin quantum state of Ce(3+) ion onto the polarization state of the emitted
      photon and represents the quantum interface between a single spin and a single
      photon.

PMID- 24093231
TI  - NADPH oxidases in lung health and disease.
AB  - SIGNIFICANCE: The evolution of the lungs and circulatory systems in vertebrates
      ensured the availability of molecular oxygen (O2; dioxygen) for aerobic cellular
      metabolism of internal organs in large animals. O2 serves as the physiologic
      terminal acceptor of mitochondrial electron transfer and of the NADPH oxidase
      (Nox) family of oxidoreductases to generate primarily water and reactive oxygen
      species (ROS), respectively. RECENT ADVANCES: The purposeful generation of ROS by
      Nox family enzymes suggests important roles in normal physiology and adaptation,
      most notably in host defense against invading pathogens and in cellular
      signaling. CRITICAL ISSUES: However, there is emerging evidence that, in the
      context of chronic stress and/or aging, Nox enzymes contribute to the
      pathogenesis of a number of lung diseases. FUTURE DIRECTIONS: Here, we review
      evolving functions of Nox enzymes in normal lung physiology and emerging
      pathophysiologic roles in lung disease.

PMID- 24093237
TI  - Nonequilibrium microcanonical and canonical ensembles and their equivalence.
AB  - Generalizations of the microcanonical and canonical ensembles for paths of Markov
      processes have been proposed recently to describe the statistical properties of
      nonequilibrium systems driven in steady states. Here, we propose a theory of
      these ensembles that unifies and generalizes earlier results and show how it is
      fundamentally related to the large deviation properties of nonequilibrium
      systems. Using this theory, we provide conditions for the equivalence of
      nonequilibrium ensembles, generalizing those found for equilibrium systems,
      construct driven physical processes that generate these ensembles, and rederive
      in a simple way known and new product rules for their transition rates. A
      nonequilibrium diffusion model is used to illustrate these results. 

PMID- 24093238
TI  - Adiabatic tracking of a state: a new route to nonequilibrium physics.
AB  - We present a novel numerical approach to track the response of a quantum system
      to an external perturbation that is progressively switched on. The method is
      applied, within the framework of the density matrix renormalization group
      technique, to track current-carrying states of interacting fermions in one
      dimension and in the presence of an Aharonov-Bohm magnetic flux. This protocol
      allows us to access highly excited states. We also discuss the connection with
      the entanglement entropy of these excited states. 

PMID- 24093239
TI  - Bulk viscosity and conformal symmetry breaking in the dilute Fermi gas near
      unitarity.
AB  - The dilute Fermi gas at unitarity is scale invariant and its bulk viscosity
      vanishes. We compute, in the high temperature limit, the leading contribution to
      the bulk viscosity when the scattering length is not infinite. A measure of scale
      breaking is provided by the ratio (P-2pih/3epsilon)/P, where P is the pressure
      and E is the energy density. At high temperature this ratio scales as zlambda/a,
      where z is the fugacity, lambda is the thermal wavelength, and a is the
      scattering length. We show that the bulk viscosity zeta scales as the second
      power of this parameter, zeta~(zlambda/a)(2)lambda(-3).

PMID- 24093240
TI  - Constraints on the formation and structure of Langmuir eigenmodes in the solar
      wind.
AB  - Localized Langmuir waves are commonly observed in space plasmas and are a
      potential source of radio waves. Using electric field data from STEREO, it is
      shown that these localized Langmuir waves are eigenmodes of density wells
      estimated independently. An analytic model is developed for the eigenmode
      frequencies. The inferred depths and widths of the density wells typically only
      allow the zeroth-order Langmuir eigenmode to form, explaining the preponderance
      of single-peaked waveforms. More complicated waveforms are shown to be consistent
      with single eigenmode solutions of more complicated density profiles. The
      inferred depth of the density well increases with Langmuir wave intensity,
      consistent with the ponderomotive force but not wave packet collapse. 

PMID- 24093241
TI  - TeV-PeV neutrinos from low-power gamma-ray burst jets inside stars.
AB  - We study high-energy neutrino production in collimated jets inside progenitors of
      gamma-ray bursts (GRBs) and supernovae, considering both collimation and internal
      shocks. We obtain simple, useful constraints, using the often overlooked point
      that shock acceleration of particles is ineffective at radiation-mediated shocks.
      Classical GRBs may be too powerful to produce high-energy neutrinos inside stars,
      which is consistent with IceCube nondetections. We find that ultralong GRBs avoid
      such constraints and detecting the TeV signal will support giant progenitors.
      Predictions for low-power GRB classes including low-luminosity GRBs can be
      consistent with the astrophysical neutrino background IceCube may detect, with a
      spectral steepening around PeV. The models can be tested with future GRB
      monitors. 

PMID- 24093242
TI  - Particlelike distributions of the Higgs field nonminimally coupled to gravity.
AB  - When the Higgs field is nonminimally coupled to gravity, there exists a family of
      spherically symmetric particlelike solutions to the field equations. These
      monopoles are the only globally regular and asymptotically flat distributions
      with finite energy of the Higgs field around compact objects. Moreover,
      spontaneous scalarization is strongly amplified for specific values of their mass
      and compactness. 

PMID- 24093243
TI  - Neutrino signature of supernova hydrodynamical instabilities in three dimensions.
AB  - The first full-scale three-dimensional core-collapse supernova (SN) simulations
      with sophisticated neutrino transport show pronounced effects of the standing
      accretion shock instability (SASI) for two high-mass progenitors (20 and 27
      M([Symbol: see text])). In a low-mass progenitor (11.2 M([Symbol: see text])),
      large-scale convection is the dominant nonradial hydrodynamic instability in the
      postshock accretion layer. The SASI-associated modulation of the neutrino signal
      (80 Hz in our two examples) will be clearly detectable in IceCube or the future
      Hyper-Kamiokande detector, depending on progenitor properties, distance, and
      observer location relative to the main SASI sloshing direction. The neutrino
      signal from the next galactic SN can, therefore, diagnose the nature of the
      hydrodynamic instability.

PMID- 24093244
TI  - Von Karman energy decay and heating of protons and electrons in a kinetic
      turbulent plasma.
AB  - Decay in time of undriven weakly collisional kinetic plasma turbulence in systems
      large compared to the ion kinetic scales is investigated using fully
      electromagnetic particle-in-cell simulations initiated with transverse flow and
      magnetic disturbances, constant density, and a strong guide field. The observed
      energy decay is consistent with the von Karman hypothesis of similarity decay, in
      a formulation adapted to magnetohydrodyamics. Kinetic dissipation occurs at small
      scales, but the overall rate is apparently controlled by large scale dynamics. At
      small turbulence amplitudes the electrons are preferentially heated. At larger
      amplitudes proton heating is the dominant effect. In the solar wind and corona
      the protons are typically hotter, suggesting that these natural systems are in
      the large amplitude turbulence regime. 

PMID- 24093245
TI  - Volume independence in the large N limit and an emergent fermionic symmetry.
AB  - Large-N volume independence in circle-compactified QCD with adjoint Weyl fermions
      implies the absence of any phase transitions as the radius is dialed to
      arbitrarily small values. This class of theories is believed to possess a
      Hagedorn density of hadronic states. It turns out that these properties are in
      apparent tension with each other, because a Hagedorn density of states typically
      implies a phase transition at some finite radius. This tension is resolved if
      there are degeneracies between the spectra of bosonic and fermionic states, as
      happens in the N(f) = 1 supersymmetric case. Resolution of the tension for N(f)
      >1 then suggests the emergence of a fermionic symmetry at large N, where there is
      no supersymmetry. We can escape the Coleman-Mandula theorem since the N =
      infinity theory is free, with a trivial S matrix. We show an example of such a
      spectral degeneracy in a nonsupersymmetric toy example which has a Hagedorn
      spectrum.

PMID- 24093246
TI  - Time-dependent Hartree-Fock solution of Gross-Neveu models: twisted-kink
      constituents of baryons and breathers.
AB  - We find the general solution to the time-dependent Hartree-Fock problem for the
      Gross-Neveu models, with both discrete (GN(2)) and continuous [Nambu-Jona-Lasinio
      (NJL(2))] chiral symmetry. We find new multibaryon, multibreather, and twisted
      breather solutions, and show that all GN(2) baryons and breathers are composed of
      constituent twisted kinks of the NJL(2) model.

PMID- 24093247
TI  - Spin-3 gravity in three-dimensional flat space.
AB  - We present the first example of a nontrivial higher spin theory in three
      dimensional flat space. We propose flat-space boundary conditions and prove their
      consistency for this theory. We find that the asymptotic symmetry algebra is a
      (centrally extended) higher spin generalization of the Bondi-Metzner-Sachs
      algebra, which we describe in detail. We also address higher spin analogues of
      flat space cosmology solutions and possible generalizations. 

PMID- 24093248
TI  - Electroweak Sudakov corrections to new physics searches at the LHC.
AB  - We compute the one-loop electroweak Sudakov corrections to the production process
      Z(nunu)+n jets, with n=1, 2, 3, in pp collisions at the LHC. It represents the
      main irreducible background to new physics searches at the energy frontier. The
      results are obtained at the leading and next-to-leading logarithmic accuracy by
      implementing the general algorithm of Denner and Pozzorini in the event generator
      for multiparton processes alpgen. For the standard selection cuts used by the
      ATLAS and CMS Collaborations, we show that the Sudakov corrections to the
      relevant observables can grow up to -40% at sqrt[s ]= 14 TeV. We also include the
      contribution due to undetected real radiation of massive gauge bosons, to show to
      what extent the partial cancellation with the large negative virtual corrections
      takes place in realistic event selections.

PMID- 24093249
TI  - Hunting mixed top squark decays.
AB  - We point out that, in the irreducible natural supersymmetric spectrum, top
      squarks have comparable branching fractions to chargino-bottom and neutralino-top
      final states in the vast bulk of parameter space, provided only that both decay
      modes are kinematically accessible. The total top squark pair branching fractions
      into tt + MET (MET=missing transverse energy) can therefore be reduced to O(50%),
      whereas bb + X branching fractions are typically much smaller, O(10%), thus
      limiting the reach of traditional top squark searches. We propose a new top
      squark search targeting the asymmetric final state t[over~]t[over~]* ->
      t(chi)(0)b(chi)(-) +H.c., which can restore sensitivity to natural top squarks in
      the 7 and 8 TeV LHC runs. In addition, we present a new variable, topness, which
      efficiently suppresses the dominant top backgrounds to semileptonic top partner
      searches. We demonstrate the utility of topness in both our asymmetric search
      channel and traditional t[over~]t[over ~](*) ->tt[over-]+MET searches and show
      that it matches or outperforms existing variables.

PMID- 24093250
TI  - New probe of naturalness.
AB  - Any new scalar fields that perturbatively solve the hierarchy problem by
      stabilizing the Higgs boson mass also generate new contributions to the Higgs
      boson field-strength renormalization, irrespective of their gauge representation.
      These new contributions are physical, and in explicit models their magnitude can
      be inferred from the requirement of quadratic divergence cancellation; hence,
      they are directly related to the resolution of the hierarchy problem. Upon
      canonically normalizing the Higgs field, these new contributions lead to
      modifications of Higgs couplings that are typically great enough that the
      hierarchy problem and the concept of electroweak naturalness can be probed
      thoroughly within a precision Higgs boson program. Specifically, at a lepton
      collider this can be achieved through precision measurements of the Higgs boson
      associated production cross section. This would lead to indirect constraints on
      perturbative solutions to the hierarchy problem in the broadest sense, even if
      the relevant new fields are gauge singlets. 

PMID- 24093251
TI  - Production of J / psi + eta(c) versus J / psi + J / psi at the LHC: importance of
      real alpha(s)(5) corrections.
AB  - We proceed for the first time to the evaluation of the Born cross section for J /
      psi + eta(c) production, namely, via g + g -> J/psi+ eta(c) + g, and show that it
      has a harder P(T) spectrum than the J/psi-pair yield at the Born level. If one
      stuck to a comparison at the Born level, one would conclude that J / psi + eta(c)
      production would surpass that of J / psi + J / psi at large P(T). This is
      nonetheless not the case since J / psi-pair production, as for single J / psi,
      receives leading-P(T) contributions at higher orders in alpha(s). We also present
      the first evaluation of these leading-P(T) next-to-leading order contributions.
      These are indeed significant for increasing P(T) and are of essential relevance
      for comparison with forthcoming data. We also compute kinematic correlations
      relevant for double-parton-scattering studies. Finally, we evaluate the
      polarization of a J/psi accompanied by either an eta(c) or a J/psi and another
      light parton. These results may be of great help to understand the polarization
      of quarkonia produced at high energies.

PMID- 24093252
TI  - First use of high-frequency intensity modulation of narrow-linewidth laser light
      and its application in determination of 206,205,204Fr ground-state properties.
AB  - Collinear laser spectroscopy was performed on the nuclear ground states of the
      neutron-deficient isotopes (206,205,204)Fr. A new technique was developed to
      suppress hyperfine pumping in collinear laser spectroscopy of atoms. This
      involved high-frequency intensity modulation of narrow-linewidth laser light
      using fast-switching electro-optical modulators. The nuclear ground-state spins
      of (206,205,204)Fr were determined to be 3, 9/2, and 3, respectively. Both the
      changes in mean-squared charge radii and nuclear magnetic dipole moments indicate
      a departure from single-particle estimates.

PMID- 24093253
TI  - First principles description of the giant dipole resonance in 16O.
AB  - We present a calculation of the giant dipole resonance in (16)O based on a
      nucleon-nucleon (NN) interaction from chiral effective field theory that
      reproduces NN scattering data with high accuracy. By merging the Lorentz integral
      transform and the coupled-cluster methods, we extend the previous theoretical
      limits for breakup observables in light nuclei with mass numbers (A <= 7) and
      address the collective giant dipole resonance of (16)O. We successfully benchmark
      the new approach against virtually exact results from the hyperspherical
      harmonics method in (4)He. Our results for (16)O reproduce the position and the
      total strength (bremsstrahlung sum rule) of the dipole response very well. When
      compared to the cross section from photoabsorption experiments, the theoretical
      curve exhibits a smeared form of the peak. The tail region between 40 and 100 MeV
      is reproduced within uncertainties.

PMID- 24093255
TI  - Near-edge x-ray absorption fine structures revealed in core ionization
      photoelectron spectroscopy.
AB  - Simultaneous core ionization and core excitation have been observed in the
      C(2)H(2n) (n=1, 2, 3) molecular series using synchrotron radiation and a magnetic
      bottle time-of-flight electron spectrometer. Rich satellite patterns
      corresponding to (K(-2)V) core excited states of the K(-1) molecular ions have
      been identified by detecting in coincidence the photoelectron with the two Auger
      electrons resulting from the double core hole relaxation. A theoretical model is
      proposed providing absolute photoionization cross sections and revealing clear
      signatures of direct (monopolar) and conjugate (dipolar near-edge x-ray
      absorption fine structure) shakeup lines of comparable magnitude.

PMID- 24093256
TI  - High-order harmonic generation spectroscopy of correlation-driven electron hole
      dynamics.
AB  - We show how high-order harmonic generation spectroscopy can be used to follow
      correlation-driven electron hole dynamics with attosecond time resolution. The
      technique is applicable both to normal Auger transitions and to electron hole
      migration processes that do not lead to secondary electron emission. We
      theoretically simulate the proposed spectroscopy for M(4,5)NN Auger decay in Kr
      and for correlation-driven inner-valence hole dynamics in trans-butadiene and
      propanal.

PMID- 24093254
TI  - Results on neutrinoless double-beta decay of 76Ge from phase I of the GERDA
      experiment.
AB  - Neutrinoless double beta decay is a process that violates lepton number
      conservation. It is predicted to occur in extensions of the standard model of
      particle physics. This Letter reports the results from phase I of the Germanium
      Detector Array (GERDA) experiment at the Gran Sasso Laboratory (Italy) searching
      for neutrinoless double beta decay of the isotope (76)Ge. Data considered in the
      present analysis have been collected between November 2011 and May 2013 with a
      total exposure of 21.6 kg yr. A blind analysis is performed. The background index
      is about 1 * 10(-2) counts/(keV kg yr) after pulse shape discrimination. No
      signal is observed and a lower limit is derived for the half-life of neutrinoless
      double beta decay of (76)Ge, T(1/2)(0nu) >2.1 * 10(25) yr (90% C.L.). The
      combination with the results from the previous experiments with (76)Ge yields
      T(1/2)(0nu)>3.0 * 10(25) yr (90% C.L.).

PMID- 24093257
TI  - Boosting photoabsorption by attosecond control of electron correlation.
AB  - Electron correlation plays an essential role in a wide range of fundamentally
      important many-body phenomena in modern physics and chemistry. An example is the
      importance of electron-electron correlation in multiple ionization of
      multielectron atoms and molecules exposed to intense laser pulses. Manipulating
      the dynamic electron correlation in such photoinduced processes is a crucial step
      toward the coherent control of chemical reactions and photobiological processes.
      The generation of an attosecond extreme ultraviolet (EUV) pulse may enable such
      controls. Here, we show for the first time, from full-dimensional ab initio
      calculations of double ionization of helium in intense laser pulses (lambda = 780
      nm), that the electron-electron interactions can be instantaneously tuned using a
      time-delayed attosecond EUV pulse. Consequently, the probability of producing
      energetic electrons from excessive photoabsorption can be enhanced by an order of
      magnitude, by the attosecond control of electron-electron correlation.

PMID- 24093258
TI  - Proton ejection from molecular hydride clusters exposed to strong x-ray pulses.
AB  - Clusters consisting of small molecules containing hydrogen do eject fast protons
      when illuminated by short x-ray pulses. A suitable overall charging of the
      cluster controlled by the x-ray intensity induces electron migration from the
      surface to the bulk leading to efficient segregation of the protons and to a
      globally hindered explosion of the heavy atoms even outside the screened volume.
      We investigate this peculiar effect systematically along the isoelectronic
      sequence of methane over ammonia and water to the atomic limit of neon as a
      reference. In contrast to core-shell systems where the outer shell is sacrificed
      to reduce radiation damage, the intricate proton dynamics of hydride clusters
      allows one to keep the entire backbone of heavy atoms intact. 

PMID- 24093259
TI  - Protected state enhanced quantum metrology with interacting two-level ensembles.
AB  - Ramsey interferometry is routinely used in quantum metrology for the most
      sensitive measurements of optical clock frequencies. Spontaneous decay to the
      electromagnetic vacuum ultimately limits the interrogation time and thus sets a
      lower bound to the optimal frequency sensitivity. In dense ensembles of two-level
      systems, the presence of collective effects such as superradiance and dipole
      dipole interaction tends to decrease the sensitivity even further. We show that
      by a redesign of the Ramsey-pulse sequence to include different rotations of
      individual spins that effectively fold the collective state onto a state close to
      the center of the Bloch sphere, partial protection from collective decoherence is
      possible. This allows a significant improvement in the sensitivity limit of a
      clock transition detection scheme over the conventional Ramsey method for
      interacting systems and even for noninteracting decaying atoms. 

PMID- 24093260
TI  - Narrow band source of transform-limited photon pairs via four-wave mixing in a
      cold atomic ensemble.
AB  - We observe narrow band pairs of time-correlated photons of wavelengths 776 and
      795 nm from nondegenerate four-wave mixing in a laser-cooled atomic ensemble of
      ^{87}Rb using a cascade decay scheme. Coupling the photon pairs into single mode
      fibers, we observe an instantaneous rate of 7700 pairs per second with silicon
      avalanche photodetectors, and an optical bandwidth below 30 MHz. Detection events
      exhibit a strong correlation in time [g((2))(tau = 0) ~ 5800] and a high coupling
      efficiency indicated by a pair-to-single ratio of 23%. The violation of the
      Cauchy-Schwarz inequality by a factor of 8.4 * 10(6) indicates a strong
      nonclassical correlation between the generated fields, while a Hanbury Brown
      Twiss experiment in the individual photons reveals their thermal nature. The
      comparison between the measured frequency bandwidth and 1/e decay time of g((2))
      indicates a transform-limited spectrum of the photon pairs. The narrow bandwidth
      and brightness of our source makes it ideal for interacting with atomic ensembles
      in quantum communication protocols.

PMID- 24093261
TI  - Carrier-envelope phase effects of a single attosecond pulse in two-color
      photoionization.
AB  - The attosecond streak camera method is usually implemented to characterize the
      temporal phase and amplitude of isolated attosecond pulses produced by high-order
      harmonic generation. This approach, however, does not provide any information
      about the carrier-envelope phase of the attosecond pulses. We demonstrate that
      the photoelectron spectra generated by an attosecond waveform and an intense
      synchronized infrared field are sensitive to the electric field of the attosecond
      pulse. The dependence on the carrier-envelope phase of the attosecond pulse is
      understood in terms of the coherent superposition of two photoelectron wave
      packets. This effect suggests an experimentally feasible method for complete
      reconstruction of attosecond waveforms. 

PMID- 24093262
TI  - Self-induced mode transformation in nonlocal nonlinear media.
AB  - We report on the first experimental observation of self-induced optical mode
      transformations in nonlocal nonlinear media. We show that the quadrupole Hermite
      Gaussian mode experiences complex nonlinear dynamics in a nematic liquid crystal,
      including power-dependent conversion into a radially symmetric Laguerre-Gaussian
      mode. The physical mechanism responsible for self-induced transformation is the
      excitation of internal modes of a metastable quadrupole nonlocal soliton and its
      subsequent transmutation into a robust soliton with a bright peak surrounded by a
      bright ring. We also observe the onset of transformations of higher-order modes,
      proving the generic character of this nonlinear phenomenon. 

PMID- 24093263
TI  - Eigenvalue statistics as an indicator of integrability of nonequilibrium density
      operators.
AB  - We propose to quantify the complexity of nonequilibrium steady state density
      operators, as well as of long-lived Liouvillian decay modes, in terms of the
      level spacing distribution of their spectra. Based on extensive numerical studies
      in a variety of models, some solvable and some unsolved, we conjecture that the
      integrability of density operators (e.g., the existence of an algebraic procedure
      for their construction in finitely many steps) is signaled by a Poissonian level
      statistics, whereas in the generic nonintegrable cases one finds level statistics
      of a Gaussian unitary ensemble of random matrices. Eigenvalue statistics can
      therefore be used as an efficient tool to identify integrable quantum
      nonequilibrium systems. 

PMID- 24093264
TI  - Completing the mechanical energy pathways in turbulent Rayleigh-Benard
      convection.
AB  - A new, more complete view of the mechanical energy budget for Rayleigh-Benard
      convection is developed and examined using three-dimensional numerical
      simulations at large Rayleigh numbers and Prandtl number of 1. The driving role
      of available potential energy is highlighted. The relative magnitudes of
      different energy conversions or pathways change significantly over the range of
      Rayleigh numbers Ra ~ 10(7)-10(13). At Ra < 10(7) small-scale turbulent motions
      are energized directly from available potential energy via turbulent buoyancy
      flux and kinetic energy is dissipated at comparable rates by both the large- and
      small-scale motions. In contrast, at Ra >= 10(10) most of the available potential
      energy goes into kinetic energy of the large-scale flow, which undergoes shear
      instabilities that sustain small-scale turbulence. The irreversible mixing is
      largely confined to the unstable boundary layer, its rate exactly equal to the
      generation of available potential energy by the boundary fluxes, and mixing
      efficiency is 50%.

PMID- 24093265
TI  - Magnetic field variation caused by rotational speed change in a
      magnetohydrodynamic dynamo.
AB  - We have performed numerical magnetohydrodynamic dynamo simulations in a spherical
      shell with rotational speed or length-of-day (LOD) variation, which is motivated
      by correlations between geomagnetic field and climatic variations with ice and
      non-ice ages. The results show that LOD variation leads to magnetic field
      variation whose amplitude is considerably larger than that of LOD variation. The
      heat flux at the outer sphere and the zonal flow also change. The mechanism of
      the magnetic field variation due to LOD variation is also found. The keys are
      changes of dynamo activity and Joule heating.

PMID- 24093266
TI  - Fast dynamos in spherical boundary-driven flows.
AB  - We numerically demonstrate the feasibility of kinematic fast dynamos for a class
      of time-periodic axisymmetric flows of conducting fluid confined inside a sphere.
      The novelty of our work is in considering the realistic flows, which are self
      consistently determined from the Navier-Stokes equation with specified boundary
      driving. Such flows can be achieved in a new plasma experiment, whose spherical
      boundary is capable of differential driving of plasma flows in the azimuthal
      direction. We show that magnetic fields are self-excited over a range of flow
      parameters such as amplitude and frequency of flow oscillations, fluid Reynolds
      (Re) and magnetic Reynolds (Rm) numbers. In the limit of large Rm, the growth
      rates of the excited magnetic fields are of the order of the advective time
      scales and practically independent of Rm, which is an indication of the fast
      dynamo. 

PMID- 24093267
TI  - Mode conversion of waves in the ion-cyclotron frequency range in magnetospheric
      plasmas.
AB  - Waves in the ion-cyclotron range of frequencies with linear polarization detected
      by satellites can be useful for estimating the heavy ion concentrations in
      planetary magnetospheres. These waves are considered to be driven by mode
      conversion (MC) of the fast magnetosonic waves at the ion-ion hybrid resonances.
      In this Letter, we derive analytical expressions for the MC efficiency and
      tunneling of waves through the MC layer. We evaluate the particular parallel wave
      numbers for which MC is efficient for arbitrary heavy ion/proton ratios and
      discuss the interpretation of the experimental observations. 

PMID- 24093269
TI  - Quantum bound of the shear viscosity of a strongly coupled plasma.
AB  - String theory methods led to the hypothesis that the ratio of a shear viscosity
      coefficient to the volume density of entropy of any physical system has a lower
      bound. Systems with strong coupling have a small viscosity as compared to weakly
      coupled plasmas in which the viscosity is proportional to the mean free path.
      Here, we have estimated the fully ionized strongly coupled plasma viscosity based
      on the dynamic experimental data on electrical conductivity and have shown that
      the ratio of viscosity to entropy of the strongly coupled plasma is very close to
      that of the lower bound predicted by the string theory. 

PMID- 24093268
TI  - Effects of magnetic shear on toroidal rotation in tokamak plasmas with lower
      hybrid current drive.
AB  - Application of lower hybrid (LH) current drive in tokamak plasmas can induce both
      co- and countercurrent directed changes in toroidal rotation, depending on the
      core q profile. For discharges with q(0) <1, rotation increments in the
      countercurrent direction are observed. If the LH-driven current is sufficient to
      suppress sawteeth and increase q(0) above unity, the core toroidal rotation
      change is in the cocurrent direction. This change in sign of the rotation
      increment is consistent with a change in sign of the residual stress (the
      divergence of which constitutes an intrinsic torque that drives the flow) through
      its dependence on magnetic shear.

PMID- 24093270
TI  - Generation of whistler-wave heated discharges with planar resonant RF networks.
AB  - Magnetized plasma discharges generated by a planar resonant rf network are
      investigated. A regime transition is observed above a magnetic field threshold,
      associated with rf waves propagating in the plasma and which present the
      characteristics of whistler waves. These wave heated regimes can be considered as
      analogous to conventional helicon discharges, but in planar geometry. 

PMID- 24093271
TI  - Magnetically generated spin-orbit coupling for ultracold atoms.
AB  - We present a new technique for producing two- and three-dimensional Rashba-type
      spin-orbit couplings for ultracold atoms without involving light. The method
      relies on a sequence of pulsed inhomogeneous magnetic fields imprinting suitable
      phase gradients on the atoms. For sufficiently short pulse durations, the time
      averaged Hamiltonian well approximates the Rashba Hamiltonian. Higher order
      corrections to the energy spectrum are calculated exactly for spin-1/2 and
      perturbatively for higher spins. The pulse sequence does not modify the form of
      rotationally symmetric atom-atom interactions. Finally, we present a
      straightforward implementation of this pulse sequence on an atom chip. 

PMID- 24093272
TI  - Two-dimensional ferromagnetism of a 3He film: influence of weak frustration.
AB  - (3)He films adsorbed on the atomically flat surface of graphite provide a model
      system for the study of two-dimensional magnetism on a triangular lattice. We
      have made a study of the regime in which the T=0 ground state of the second (3)He
      layer is a fully polarized ferromagnet. NMR, using broadband SQUID detection, at
      a range of low fields above the spin-flop transition, and over a wide temperature
      range 0.3-200 mK, has enabled us to disentangle the influence of sample finite
      size effects and magnetic field on the spin-wave spectrum. We demonstrate that
      the spin-wave spectrum is governed by a different effective exchange constant
      than that determining the high temperature magnetism. This is understood in terms
      of frustrated atomic ring exchange.

PMID- 24093273
TI  - Stability of a unitary Bose gas.
AB  - We study the stability of a thermal (39)K Bose gas across a broad Feshbach
      resonance, focusing on the unitary regime, where the scattering length a exceeds
      the thermal wavelength lambda. We measure the general scaling laws relating the
      particle-loss and heating rates to the temperature, scattering length, and atom
      number. Both at unitarity and for positive a<<lambda we find agreement with three
      body theory. However, for a<0 and away from unitarity, we observe significant
      four-body decay. At unitarity, the three-body loss coefficient, L(3) proportional
      lambda(4), is 3 times lower than the universal theoretical upper bound. This
      reduction is a consequence of species-specific Efimov physics and makes (39)K
      particularly promising for studies of many-body physics in a unitary Bose gas.

PMID- 24093274
TI  - Embedding quasicrystals in a periodic cell: dynamics in quasiperiodic structures.
AB  - We introduce a construction to "periodize" a quasiperiodic lattice of obstacles,
      i.e., embed it into a unit cell in a higher-dimensional space, reversing the
      projection method used to form quasilattices. This gives an algorithm for
      simulating dynamics, as well as a natural notion of uniform distribution, in
      quasiperiodic structures. It also shows the generic existence of channels, where
      particles travel without colliding, up to a critical obstacle radius, which we
      calculate for a Penrose tiling. As an application, we find superdiffusion in the
      presence of channels, and a subdiffusive regime when obstacles overlap. 

PMID- 24093275
TI  - Effect of temperature and density fluctuations on the spatially heterogeneous
      dynamics of glass-forming Van der Waals liquids under high pressure.
AB  - In this Letter, we show how temperature and density fluctuations affect the
      spatially heterogeneous dynamics at ambient and elevated pressures. By using high
      pressure experimental data for van der Waals liquids, we examine contributions of
      the temperature and density fluctuations to the dynamics heterogeneity. We show
      that the dynamic heterogeneity decreases significantly with increasing pressure
      at a constant structural relaxation time (isochronal condition), while the
      broadening of the relaxation spectrum remains constant. This observation
      questions the relationship between spectral broadening and dynamic heterogeneity.

PMID- 24093276
TI  - Breakup of a transient wetting layer in polymer blend thin films: unification
      with 1D phase equilibria.
AB  - We show that lateral phase separation in polymer blend thin films can proceed via
      the formation of a transient wetting layer which breaks up to give a laterally
      segregated film. We show that the growth of lateral inhomogeneities at the walls
      in turn causes the distortion of the interface in the transient wetting layer. By
      addressing the 1D phase equilibria of a polymer blend thin film confined between
      selectively attracting walls, we show that the breakup of a transient wetting
      layer is due to wall-blend interactions; there are multiple values of the volume
      fraction at the walls which solve equilibrium boundary conditions. This mechanism
      of lateral phase separation should be general. 

PMID- 24093277
TI  - Infrared spectroscopy of molecular submonolayers on surfaces by infrared scanning
      tunneling microscopy: tetramantane on Au111.
AB  - We have developed a new scanning-tunneling-microscopy-based spectroscopy
      technique to characterize infrared (IR) absorption of submonolayers of molecules
      on conducting crystals. The technique employs a scanning tunneling microscope as
      a precise detector to measure the expansion of a molecule-decorated crystal that
      is irradiated by IR light from a tunable laser source. Using this technique, we
      obtain the IR absorption spectra of [121]tetramantane and [123]tetramantane on
      Au(111). Significant differences between the IR spectra for these two isomers
      show the power of this new technique to differentiate chemical structures even
      when single-molecule-resolved scanning tunneling microscopy (STM) images look
      quite similar. Furthermore, the new technique was found to yield significantly
      better spectral resolution than STM-based inelastic electron tunneling
      spectroscopy, and to allow determination of optical absorption cross sections.
      Compared to IR spectroscopy of bulk tetramantane powders, infrared scanning
      tunneling microscopy (IRSTM) spectra reveal narrower and blueshifted vibrational
      peaks for an ordered tetramantane adlayer. Differences between bulk and surface
      tetramantane vibrational spectra are explained via molecule-molecule
      interactions. 

PMID- 24093278
TI  - Anomalous fast dynamics of adsorbate overlayers near an incommensurate structural
      transition.
AB  - We investigate the dynamics of a compressively strained adsorbed layer on a
      periodic substrate via a simple two-dimensional model that admits striped and
      hexagonal incommensurate phases. We show that the mass transport is superfast
      near the striped-hexagonal phase boundary and in the hexagonal phase. For an
      initial step profile separating a bare substrate region (or "hole") from the rest
      of a striped incommensurate phase, the superfast domain wall dynamics leads to a
      bifurcation of the initial step profile into two interfaces or profiles
      propagating in opposite directions with a hexagonal phase in between. This yields
      a theoretical understanding of the recent experiments for the Pb/Si(111) system. 

PMID- 24093279
TI  - Atomic structure affects the directional dependence of friction.
AB  - Friction between two objects can be understood by the making, stretching, and
      breaking of thousands of atomic-scale asperities. We have probed single atoms in
      a nonisotropic surface [the H-terminated Si(100) surface] with a lateral force
      microscope operating in noncontact mode. We show that these forces are measurably
      different, depending upon the direction. Experimentally, these differences are
      observable in both the line profiles and the maximum stiffnesses. Density
      functional theory calculations show a concerted motion of the whole Si dimer
      during the tip-sample interaction. These results demonstrate that on an asperity
      by-asperity basis, the surface atomic structure plays a strong role in the
      directional dependence of friction. 

PMID- 24093280
TI  - Impact of lithium-ion ordering on surface electronic states of Li(x)CoO2.
AB  - Li(x)CoO(2) exhibits intriguing electronic properties due to a strong electron
      correlation and complex interplay between Co and Li ions. However, fundamental
      understanding of the nanoscale distribution of Li ions and its effect on the
      electronic properties remains unclear. We use scanning tunneling microscopy and
      density functional theory to elucidate the degree of Li(x)CoO(2) surface
      electronic state modification that can be achieved by Li ordering. The surface Li
      ions are highly mobile and preferentially form a (1 * 1) hexagonal lattice,
      whereas the surface CoO(2) layer shows metallic and insulating phases, indicating
      the coexistence of ordered and disordered Li ions in the subsurface layer. These
      results provide evidence of novel electronic properties produced by spatially
      inhomogeneous Li-ordering patterns.

PMID- 24093281
TI  - Layer-by-layer evolution of a two-dimensional electron gas near an oxide
      interface.
AB  - We report the momentum-resolved measurement of a two-dimensional electron gas at
      the LaTiO(3)/SrTiO(3) interface by angle-resolved photoemission spectroscopy
      (ARPES). Thanks to an advanced sample preparation technique, the orbital
      character of the conduction electrons and the electronic correlations can be
      accessed quantitatively as each unit cell layer is added. We find that all of
      these quantities change dramatically with distance from the interface. These
      findings open the way to analogous studies on other heterostructures, which are
      traditionally a forbidden field for ARPES.

PMID- 24093282
TI  - Derivative discontinuity in the strong-interaction limit of density-functional
      theory.
AB  - We generalize the exact strong-interaction limit of the exchange-correlation
      energy of Kohn-Sham density functional theory to open systems with fluctuating
      particle numbers. When used in the self-consistent Kohn-Sham procedure on
      strongly interacting systems, this functional yields exact features crucial for
      important applications such as quantum transport. In particular, the steplike
      structure of the highest-occupied Kohn-Sham eigenvalue is very well captured,
      with accurate quantitative agreement with exact many-body chemical potentials.
      While it can be shown that a sharp derivative discontinuity is present only in
      the infinitely strongly correlated limit, at finite correlation regimes we
      observe a slightly smoothened discontinuity, with qualitative and quantitative
      features that improve with increasing correlation. From the fundamental point of
      view, our results obtain the derivative discontinuity without making the
      assumptions used in its standard derivation, offering independent support for its
      existence. 

PMID- 24093283
TI  - Emergent heavy fermion behavior at the Wigner-Mott transition.
AB  - We study charge ordering driven by Coulomb interactions on triangular lattices
      relevant to the Wigner-Mott transition in two dimensions. Dynamical mean-field
      theory reveals the pinball liquid phase, a charge ordered metallic phase
      containing quasilocalized (pins) coexisting with itinerant (balls) electrons.
      Based on an effective periodic Anderson model for this phase, we find an
      antiferromagnetic Kondo coupling between pins and balls and strong quasiparticle
      renormalization. Non-Fermi liquid behavior can occur in such charge ordered
      systems due to the spin-flip scattering of itinerant electrons off the pins in
      analogy with heavy fermion compounds. 

PMID- 24093284
TI  - Hall drag and magnetodrag in graphene.
AB  - Massless Dirac fermions in graphene at charge neutrality form a strongly
      interacting system in which both charged and neutral (energy) modes play an
      important role. These modes are essentially decoupled in the absence of a
      magnetic field, but become strongly coupled when the field is applied. We show
      that this regime is characterized by strong magnetodrag and Hall drag,
      originating from long-range energy currents and spatial temperature gradients.
      The energy-driven effects arise in a wide temperature range, and feature an
      unusually strong dependence on field and carrier density. We argue that this
      mechanism accounts for the recently observed giant magnetodrag and Hall drag
      occurring at classically weak fields. 

PMID- 24093285
TI  - Peltier cooling and onsager reciprocity in ferromagnetic thin films.
AB  - We present direct measurements of the Peltier effect as a function of temperature
      from 77 to 325 K in Ni, Ni(80)Fe(20), and Fe thin films made using a suspended Si
      N membrane structure. Measurement of the Seebeck effect in the same films allows
      us to directly test predictions of Onsager reciprocity between the Peltier and
      Seebeck effects. The Peltier coefficient Pi is negative for both Ni and
      Ni(80)Fe(20) films and positive for the Fe film. The Fe film also exhibits a peak
      associated with the magnon drag Peltier effect. The observation of magnon drag in
      the Fe film verifies that the coupling between the phonon, magnon, and electron
      systems in the film is the same whether driven by heat current or charge current.
      The excellent agreement between Pi values predicted using the experimentally
      determined Seebeck coefficient for these films and measured values offers direct
      experimental confirmation of the Onsager reciprocity between these thermoelectric
      effects in ferromagnetic thin films near room temperature.

PMID- 24093286
TI  - Circular dichroism and superdiffusive transport at the surface of BiTeI.
AB  - We investigate the electronic states of BiTeI after the optical pumping with
      circularly polarized photons. Our data show that photoexcited electrons reach an
      internal thermalization within 300 fs of the arrival of the pump pulse. Instead,
      the dichroic contrast generated by the circularly polarized light relaxes on a
      time scale shorter than 80 fs. This result implies that orbital and spin
      polarization created by the circular pump pulse rapidly decays via manybody
      interaction. The persistent dichroism at longer delay times is due to the
      helicity dependence of superdiffussive transport. We ascribe it to the lack of
      inversion symmetry in an electronic system far from equilibrium conditions. 

PMID- 24093287
TI  - Spin-orbit splitting in single-layer MoS2 revealed by triply resonant Raman
      scattering.
AB  - Although new spintronic devices based on the giant spin-orbit splitting of single
      layer MoS(2) have been proposed, such splitting has not been studied effectively
      in experiments. This Letter reports the valence band spin-orbit splitting in
      single-layer MoS(2) for the first time, probed by the triply resonant Raman
      scattering process. We found that upon 325 nm laser irradiation, the second order
      overtone and combination Raman modes of single-layer MoS(2) are dramatically
      enhanced. Such resonant Raman enhancement arises from the electron-two-phonon
      triple resonance via the deformation potential and Frohlich interaction. As a
      sensitive and precise probe for the spin-orbit splitting, the triply resonant
      Raman scattering will provide a new and independent route to study the spin
      characteristics of MoS(2).

PMID- 24093288
TI  - Hierarchy of fractional Chern insulators and competing compressible states.
AB  - We study the phase diagram of interacting electrons in a dispersionless Chern
      band as a function of their filling. We find hierarchy multiplets of
      incompressible states at fillings nu = 1/3, 2/5, 3/7, 4/9, 5/9, 4/7, 3/5 as well
      as nu = 1/5, 2/7. These are accounted for by an analogy to Haldane
      pseudopotentials extracted from an analysis of the two-particle problem.
      Important distinctions to standard fractional quantum Hall physics are striking:
      in the absence of particle-hole symmetry in a single band, an interaction-induced
      single-hole dispersion appears, which perturbs and eventually destabilizes
      incompressible states as nu increases. For this reason, the nature of the state
      at nu = 2/3 is hard to pin down, while nu = 5/7, 4/5 do not seem to be
      incompressible in our system.

PMID- 24093289
TI  - Detection and measurement of spin-dependent dynamics in random telegraph signals.
AB  - A quantum point contact was used to observe single-electron fluctuations of a
      quantum dot in a GaAs heterostructure. The resulting random telegraph signals
      (RTS) contain statistical information about the electron spin state if the
      tunneling dynamics are spin dependent. We develop a statistical method to extract
      information about spin-dependent dynamics from RTS and use it to demonstrate that
      these dynamics can be studied in the thermal energy regime. The tunneling rates
      of each spin state are independently measured in a finite external magnetic
      field. We confirm previous findings of a decrease in overall tunneling rates for
      the spin excited state compared to the ground state as an external magnetic field
      is increased. 

PMID- 24093290
TI  - Massive symmetry breaking in LaAlO3/SrTiO3(111) quantum wells: a three-orbital
      strongly correlated generalization of graphene.
AB  - Density functional theory calculations with an on-site Coulomb repulsion term
      reveal competing ground states in (111)-oriented (LaAlO(3))(M)/(SrTiO(3))(N)
      superlattices with n-type interfaces, ranging from spin, orbitally polarized
      (with selective e(g)('), a(1g), or d(xy) occupation), Dirac point Fermi surface,
      to charge-ordered flat band phases. These phases are steered by the interplay of
      (i) Hubbard U, (ii) SrTiO(3) quantum well thickness, and (iii) crystal field
      splitting tied to in-plane strain. In the honeycomb lattice bilayer N = 2 under
      tensile strain, inversion symmetry breaking drives the system from a
      ferromagnetic Dirac point (massless Weyl semimetal) to a charge-ordered
      multiferroic (ferromagnetic and ferroelectric) flat band massive (insulating)
      phase. With increasing SrTiO(3) quantum well thickness an insulator-to-metal
      transition occurs.

PMID- 24093291
TI  - Nematicity as a probe of superconducting pairing in iron-based superconductors.
AB  - In several families of iron-based superconducting materials, a d-wave pairing
      instability may compete with the leading s-wave instability. Here, we show that
      when both states have comparable free energies, superconducting and nematic
      degrees of freedom are strongly coupled. Whereas nematic order causes a sharp
      nonanalytic increase in T(c), nematic fluctuations can change the character of
      the s-wave to d-wave transition, favoring an intermediate state that does not
      break time-reversal symmetry but does break tetragonal symmetry. The coupling
      between superconductivity and nematicity is also manifested in the strong
      softening of the shear modulus across the superconducting transition. Our results
      show that nematicity can be used as a diagnostic tool to search for
      unconventional pairing states in iron pnictides and chalcogenides.

PMID- 24093292
TI  - Imaging the three-dimensional Fermi-surface pairing near the hidden-order
      transition in URu2Si2 using angle-resolved photoemission spectroscopy.
AB  - We report angle-resolved photoemission spectroscopy experiments probing deep into
      the hidden-order state of URu(2)Si(2), utilizing tunable photon energies with
      sufficient energy and momentum resolution to detect the near Fermi-surface (FS)
      behavior. Our results reveal (i) the full itinerancy of the 5f electrons, (ii)
      the crucial three-dimensional k-space nature of the FS and its critical nesting
      vectors, in good comparison with density-functional theory calculations, and
      (iii) the existence of hot-spot lines and pairing of states at the FS, leading to
      FS gapping in the hidden-order phase.

PMID- 24093293
TI  - High cooperativity in coupled microwave resonator ferrimagnetic insulator
      hybrids.
AB  - We report the observation of strong coupling between the exchange-coupled spins
      in a gallium-doped yttrium iron garnet and a superconducting coplanar microwave
      resonator made from Nb. The measured coupling rate of 450 MHz is proportional to
      the square root of the number of exchange-coupled spins and well exceeds the loss
      rate of 50 MHz of the spin system. This demonstrates that exchange-coupled
      systems are suitable for cavity quantum electrodynamics experiments, while
      allowing high integration densities due to their spin densities of the order of
      one Bohr magneton per atom. Our results furthermore show, that experiments with
      multiple exchange-coupled spin systems interacting via a single resonator are
      within reach.

PMID- 24093294
TI  - Local conservation laws and the structure of the many-body localized states.
AB  - We construct a complete set of local integrals of motion that characterize the
      many-body localized (MBL) phase. Our approach relies on the assumption that local
      perturbations act locally on the eigenstates in the MBL phase, which is supported
      by numerical simulations of the random-field XXZ spin chain. We describe the
      structure of the eigenstates in the MBL phase and discuss the implications of
      local conservation laws for its nonequilibrium quantum dynamics. We argue that
      the many-body localization can be used to protect coherence in the system by
      suppressing relaxation between eigenstates with different local integrals of
      motion. 

PMID- 24093295
TI  - Giant magnetic susceptibility of gold nanorods detected by magnetic alignment.
AB  - We have determined the magnetic properties of single-crystalline Au nanorods in
      solution using an optically detected magnetic alignment technique. The rods
      exhibit a large anisotropy in the magnetic volume susceptibility (Deltachi(V)).
      Deltachi(V) increases with decreasing rod size and increasing aspect ratio and
      corresponds to an average volume susceptibility (chi(V)), which is drastically
      enhanced relative to bulk Au. This high value of chi(V) is confirmed by SQUID
      magnetometry and is temperature independent (between 5 and 300 K). Given this
      peculiar size, shape, and temperature dependence, we speculate that the enhanced
      chi(V) is the result of orbital magnetism due to mesoscopic electron trajectories
      within the nanorods.

PMID- 24093296
TI  - Local control of single atom magnetocrystalline anisotropy.
AB  - Individual Fe atoms on a Cu(2)N/Cu(100) surface exhibit strong magnetic
      anisotropy due to the crystal field. We show that we can controllably enhance or
      reduce this anisotropy by adjusting the relative position of a second nearby Fe
      atom, with atomic precision, in a low-temperature scanning tunneling microscope.
      Local inelastic electron tunneling spectroscopy, combined with a qualitative
      first-principles model, reveal that the change in uniaxial anisotropy is driven
      by local strain due to the presence of the second Fe atom.

PMID- 24093297
TI  - Interatomic exchange interactions for finite-temperature magnetism and
      nonequilibrium spin dynamics.
AB  - We derive ab inito exchange parameters for general noncollinear magnetic
      configurations, in terms of a multiple scattering formalism. We show that the
      general exchange formula has an anisotropiclike term even in the absence of spin
      orbit coupling, and that this term is large, for instance, for collinear
      configuration in bcc Fe, whereas for fcc Ni it is quite small. We demonstrate
      that keeping this term leads to what one should consider a biquadratic effective
      spin Hamiltonian even in the case of collinear arrangement. In noncollinear
      systems this term results in new tensor elements that are important for exchange
      interactions at finite temperatures, but they have less importance at low
      temperature. To illustrate our results in practice, we calculate for bcc Fe
      magnon spectra obtained from configuration-dependent exchange parameters, where
      the configurations are determined by finite-temperature effects. Our theory
      results in the same quantitative results as the finite-temperature neutron
      scattering experiments.

PMID- 24093298
TI  - Ballistic spreading of entanglement in a diffusive nonintegrable system.
AB  - We study the time evolution of the entanglement entropy of a one-dimensional
      nonintegrable spin chain, starting from random nonentangled initial pure states.
      We use exact diagonalization of a nonintegrable quantum Ising chain with
      transverse and longitudinal fields to obtain the exact quantum dynamics. We show
      that the entanglement entropy increases linearly with time before finite-size
      saturation begins, demonstrating a ballistic spreading of the entanglement, while
      the energy transport in the same system is diffusive. Thus, we explicitly
      demonstrate that the spreading of entanglement is much faster than the energy
      diffusion in this nonintegrable system. 

PMID- 24093299
TI  - Spin-induced optical conductivity in the spin-liquid candidate herbertsmithite.
AB  - We report a direct measurement of the low-frequency optical conductivity of large
      area single-crystal herbertsmithite, a promising spin-liquid candidate material,
      by means of terahertz time-domain spectroscopy. In the spectral range below 1.4
      THz, we observe a contribution to the real part of the in-plane conductivity
      sigma(ab)(omega) from the spin degree of freedom. This spin-induced conductivity
      exhibits a power-law dependence on frequency sigma(ab)(omega) ~ omega(beta) with
      beta ~ 1.4. Our observation is consistent with the theoretically predicted low
      frequency conductivity arising from an emergent gauge field of a gapless U(1)
      Dirac spin liquid.

PMID- 24093300
TI  - Tuning the competition between ferromagnetism and antiferromagnetism in a half
      doped manganite through magnetoelectric coupling.
AB  - We investigate the possibility of controlling the magnetic phase transition of
      the heterointerface between a half-doped manganite La(0.5)Ca(0.5)MnO(3) and a
      multiferroic BiFeO(3) (BFO) through magnetoelectric coupling. Using macroscopic
      magnetometry and element-selective x-ray magnetic circular dichroism at the Mn
      and Fe L edges, we discover that the ferroelectric polarization of BFO controls
      simultaneously the magnetization of BFO and La(0.5)Ca(0.5)MnO(3) (LCMO). X-ray
      absorption spectra at the oxygen K edge and linear dichroism at the Mn L edge
      suggest that the interfacial coupling is mainly derived from the superexchange
      between Mn and Fe t(2g) spins. The combination of x-ray absorption spectroscopy
      and mean-field theory calculations reveals that the d-electron modulation of Mn
      cations changes the magnetic coupling in LCMO, which controls the enhanced canted
      moments of interfacial BFO via the interfacial coupling. Our results demonstrate
      that the competition between ferromagnetic and antiferromagnetic instability can
      be modulated by an electric field at the heterointerface, providing another
      pathway for the electrical field control of magnetism.

PMID- 24093301
TI  - Polarization sensitive surface band structure of doped BaTiO3(001).
AB  - We present a spatial and wave-vector resolved study of the electronic structure
      of micron sized ferroelectric domains at the surface of a BaTiO(3)(001) single
      crystal. The n-type doping of the BaTiO(3) is controlled by in situ vacuum and
      oxygen annealing, providing experimental evidence of a surface paraelectric
      ferroelectric transition below a critical doping level. Real space imaging of
      photoemission threshold, core level and valence band spectra show contrast due to
      domain polarization. Reciprocal space imaging of the electronic structure using
      linearly polarized light provides unambiguous evidence for the presence of both
      in- and out-of-plane polarization with two- and fourfold symmetry, respectively.
      The results agree well with first principles calculations.

PMID- 24093302
TI  - Soft collective fluctuations governing hydrophobic association.
AB  - The interaction between two associating hydrophobic particles has traditionally
      been explained in terms of the release of entropically frustrated hydration shell
      water molecules. However, this picture cannot account for the kinetics of
      hydrophobic association and is therefore not capable of providing a microscopic
      description of the hydrophobic interaction (HI). Here, Monte Carlo simulations of
      a pair of molecular-scale apolar solutes in aqueous solution reveal the critical
      role of collective fluctuations in the hydrogen bond (HB) network for the
      microscopic picture of the HI. The main contribution to the HI is the relaxation
      of solute-water translational correlations. The existence of a heat capacity
      maximum at the desolvation barrier is shown to arise from softening of non-HB
      water fluctuations and the relaxation of many-body correlations in the labile HB
      network. The microscopic event governing the kinetics of hydrophobic association
      has turned out to be a relatively large critical collective fluctuation in
      hydration water displacing a substantial fraction of HB clusters from the inner
      to the outer region of the first hydration shell.

PMID- 24093303
TI  - Breakdown of fast-slow analysis in an excitable system with channel noise.
AB  - We consider a stochastic version of an excitable system based on the Morris-Lecar
      model of a neuron, in which the noise originates from stochastic sodium and
      potassium ion channels opening and closing. One can analyze neural excitability
      in the deterministic model by using a separation of time scales involving a fast
      voltage variable and a slow recovery variable, which represents the fraction of
      open potassium channels. In the stochastic setting, spontaneous excitation is
      initiated by ion channel noise. If the recovery variable is constant during
      initiation, the spontaneous activity rate can be calculated using Kramer's rate
      theory. The validity of this assumption in the stochastic model is examined using
      a systematic perturbation analysis. We find that, in most physically relevant
      cases, this assumption breaks down, requiring an alternative to Kramer's theory
      for excitable systems with one deterministic fixed point. We also show that an
      exit time problem can be formulated in an excitable system by considering maximum
      likelihood trajectories of the stochastic process. 

PMID- 24093304
TI  - Localization dynamics of fluids in random confinement.
AB  - The dynamics of two-dimensional fluids confined within a random matrix of
      obstacles is investigated using both colloidal model experiments and molecular
      dynamics simulations. By varying fluid and matrix area fractions in the
      experiment, we find delocalized tracer particle dynamics at small matrix area
      fractions and localized motion of the tracers at high matrix area fractions. In
      the delocalized region, the dynamics is subdiffusive at intermediate times, and
      diffusive at long times, while in the localized regime, trapping in finite
      pockets of the matrix is observed. These observations are found to agree with the
      simulation of an ideal gas confined in a weakly correlated matrix. Our results
      show that Lorentz gas systems with soft interactions are exhibiting a smoothening
      of the critical dynamics and consequently a rounded delocalization-to
      localization transition. 

PMID- 24093305
TI  - Hexatic-to-disorder transition in colloidal crystals near electrodes: rapid
      annealing of polycrystalline domains.
AB  - Colloids are known to form planar, hexagonal closed packed (hcp) crystals near
      electrodes in response to electrohydrodynamic (EHD) flow. Previous work has
      established that the EHD velocity increases as the applied ac frequency
      decreases. Here we report the existence of an order-to-disorder transition at
      sufficiently low frequencies, despite the increase in the attractive EHD driving
      force. At large frequencies (~500 Hz), spherical micron-scale particles form hcp
      crystals; as the frequency is decreased below ~250 Hz, however, the crystalline
      structure transitions to randomly closed packed (rcp). The transition is
      reversible and second order with respect to frequency, and independent
      measurements of the EHD aggregation rate confirm that the EHD driving force is
      indeed higher at the lower frequencies. We present evidence that the transition
      is instead caused by an increased particle diffusivity due to increased particle
      height over the electrode at lower frequencies, and we demonstrate that the hcp
      rcp transition facilitates rapid annealing of polycrystalline domains.

PMID- 24093306
TI  - Dynamical interplay between awareness and epidemic spreading in multiplex
      networks.
AB  - We present the analysis of the interrelation between two processes accounting for
      the spreading of an epidemic, and the information awareness to prevent its
      infection, on top of multiplex networks. This scenario is representative of an
      epidemic process spreading on a network of persistent real contacts, and a cyclic
      information awareness process diffusing in the network of virtual social contacts
      between the same individuals. The topology corresponds to a multiplex network
      where two diffusive processes are interacting affecting each other. The analysis
      using a microscopic Markov chain approach reveals the phase diagram of the
      incidence of the epidemics and allows us to capture the evolution of the epidemic
      threshold depending on the topological structure of the multiplex and the
      interrelation with the awareness process. Interestingly, the critical point for
      the onset of the epidemics has a critical value (metacritical point) defined by
      the awareness dynamics and the topology of the virtual network, from which the
      onset increases and the epidemics incidence decreases. 

PMID- 24093307
TI  - Ciguatera and scombroid fish poisoning in the United States.
AB  - BACKGROUND: Ciguatera and scombroid fish poisonings are common causes of fish
      related foodborne illness in the United States; however, existing surveillance
      systems underestimate the overall human health impact. OBJECTIVES: This study
      aimed to describe existing data on ciguatera and scombroid fish poisonings from
      outbreak and poison control center reports and to estimate the overall number of
      ciguatera and scombroid fish-poisoning illnesses, hospitalizations, and deaths in
      the United States. METHODS: We analyzed outbreak data from the Foodborne Disease
      Outbreak Surveillance Systems (FDOSS) from 2000 to 2007 and poison control center
      call data from the National Poison Data System (NPDS) from 2005 to 2009 for
      reports of ciguatera and scombroid fish poisonings. Using a statistical model
      with many inputs, we adjusted the outbreak data for undercounting due to
      underreporting and underdiagnosis to generate estimates. Underreporting and
      underdiagnosis multipliers were derived from the poison control call data and the
      published literature. RESULTS: Annually, an average of 15 ciguatera and 28
      scombroid fish-poisoning outbreaks, involving a total of 60 and 108 ill persons,
      respectively, were reported to FDOSS (2000-2007). NPDS reported an average of 173
      exposure calls for ciguatoxin and 200 exposure calls for scombroid fish poisoning
      annually (2005-2009). After adjusting for undercounting, we estimated 15,910 (90%
      credible interval [CrI] 4140-37,408) ciguatera fish-poisoning illnesses annually,
      resulting in 343 (90% CrI 69-851) hospitalizations and three deaths (90% CrI 1
      7). We estimated 35,142 (90% CrI: 10,496-78,128) scombroid fish-poisoning
      illnesses, resulting in 162 (90% CrI 0-558) hospitalizations and 0 deaths.
      CONCLUSIONS: Ciguatera and scombroid fish poisonings affect more Americans than
      reported in surveillance systems. Although additional data can improve these
      assessments, the estimated number of illnesses caused by seafood intoxication
      illuminates this public health problem. Efforts, including education, can reduce
      ciguatera and scombroid fish poisonings.

PMID- 24093308
TI  - Immunogenicity of recombinant porcine attaching and effacing-associated protein
      compared with intimin fragment in Escherichia coli O157:H7-infected mice.
AB  - Enterohemorrhagic Escherichia coli (EHEC) causes a wide spectrum of food- and
      waterborne infectious diseases, including diarrhea, hemorrhagic colitis, and even
      hemolytic-uremic syndrome. Porcine attaching and effacing-associated protein
      (Paa) was first identified in a porcine enteropathogenic E. coli strain. It has
      been proven essential in the attaching and effacing mechanism of EHEC. However,
      the immunologic function of the Paa protein has yet to be established. In the
      present study, recombinant Paa protein was overexpressed successfully in
      engineered E. coli and effectively purified to homogeneity. Comparative
      experiments were carried out in mice with a known adhesion factor (intimin) as
      reference to investigate the immunogenicity of Paa. Intraperitoneal immunization
      of Paa protein in mice elicited significantly high levels of serum immunoglobulin
      G antibodies via Th2-mediated humoral immune response. In mice challenged with E.
      coli O157:H7, Paa protein exhibited immunological effectiveness against
      pathogenic bacteria colonization and excretion in vivo. Compared with the
      intimin, Paa showed better protective effect against E. coli O157:H7 infection in
      mice, particularly those challenged with high lethal doses of the pathogen.
      Seventy percent of the mice challenged with 50 minimal lethal dose (MLD) in the
      Paa group survived, whereas only 50% survived in the intimin group. This finding
      is the first description of the immunologic function of the Paa protein. These
      attributes provide support for the development of Paa-based vaccine, which can be
      beneficial in treating infectious diseases caused by E. coli O157:H7.

PMID- 24093309
TI  - Infection rates, fevers, and associated factors in pediatric severe traumatic
      brain injury.
AB  - Abstract Infections can increase medical costs and worsen patient outcomes. Our
      aims in pediatric severe traumatic brain injury (sTBI) patients were to determine
      the infection and fever rates, and to report on associated clinical, imaging,
      treatment, and outcome factors. We included 180 sTBI patients (presedation
      Glasgow Coma Scale <= 8 and Maximum Abbreviated Injury Scale >= 4) admitted to
      our pediatric intensive care unit. Overall, 17% of sTBI patients (n=30 of 180)
      developed 36 infections, consisting primarily of urinary tract infections (UTIs;
      n=13 of 36) and ventilator-associated pneumonias (n=11 of 36). Most infections
      were nosocomial, occurring >2 days after admission. Fever was found in 36% of
      sTBI patients during the first few hospital days, but fewer than 7% of patients
      had infections. Infections occurred more frequently in sTBI patients who were
      older, heavier, and with a higher injury severity score (ISS; p<0.05). Admission
      head computed tomography imaging abnormalities (subarachnoid hemorrhage,
      intraventricular hemorrhage, and diffuse axonal injury), placement of an
      intracranial pressure (ICP) monitor, and administration of ICP-lowering therapies
      (hypertonic saline, mannitol, and thiopental) were associated with infections
      (p<0.05). Those with infections had fewer ventilator-free days, greater hospital
      lengths of stays, and were less likely to be discharged home. Logistic regression
      demonstrated that infections were independently associated with use of hypertonic
      saline (odds ratio [OR], 4.46; p=0.001) and higher ISS (OR, 1.05; p=0.028). In
      summary, infections were prevalent in sTBI patients and were associated with
      greater head-imaging abnormalities and use of ICP-lowering therapies. Hypertonic
      saline administration was strongly associated with infection, but further
      analyses are required to determine the nature of this relationship. Fever was a
      poor indicator of infection after sTBI.

PMID- 24093310
TI  - Chimney and periscope grafts observed over 2 years after their use to
      revascularize 169 renovisceral branches in 77 patients with complex aortic
      aneurysms.
AB  - PURPOSE: To evaluate the performance of periscope and/or chimney grafts (CPGs) in
      the endovascular treatment of pararenal or thoracoabdominal aneurysms using off
      the-shelf devices. METHODS: Between February 2002 and August 2012, 77 consecutive
      patients (62 men; mean age 73+/-9 years) suffering from pararenal aortic (n=55),
      thoracoabdominal (n=16), or arch to visceral artery aneurysms (n=6) were treated
      with aortic stent-graft implantation requiring chimney and/or periscope grafts to
      maintain side branch perfusion. CPGs were planned in advance and were not used as
      bailout. A standardized follow-up protocol including computed tomographic
      angiography, laboratory testing, and clinical examination was performed at 6
      weeks; 3, 6, and 12 months; and annually thereafter. RESULTS: Technical success
      was achieved in 76 (99%) patients; 1 branch stent-graft became dislocated from a
      renal artery, which could not be re-accessed. Overall, 169 target vessels (121
      renal arteries, 30 superior mesenteric arteries, 17 celiac trunks, and 1 inferior
      mesenteric artery) were addressed with the chimney graft configuration in 111 and
      the periscope graft configuration in 58. In total, 228 devices were used for the
      CPGs: 213 Viabahn stent-grafts and 15 bare metal stents. Over a mean 25+/-16
      months (range 1-121), 9 patients died of unrelated causes. Nearly all (95%) of
      the patients demonstrated a decreased or stable aneurysm size on imaging; there
      was a mean 13% shrinkage in aneurysm diameter. Twenty patients had primary type
      I/III endoleaks at discharge; in follow-up, only 3 of these were still present
      (no secondary or recurrent endoleaks were noted). Additional endovascular
      maneuvers were required for CPG-related complications in 13 patients from
      intervention throughout follow-up. Overall, 4 CPGs occluded (98% target vessel
      patency); no stent-graft migration was observed. Renal function remained stable
      in all patients. CONCLUSION: In this series, the use of CPGs has proven to be a
      feasible, safe, and effective way to treat thoracoabdominal and pararenal
      aneurysms with maintenance of blood flow to the renovisceral arteries. Nearly all
      of the aneurysms showed no increase in diameter over a >2-year mean follow-up,
      which supports the midterm adequacy of the CPG technique as a method to
      effectively revascularize branch vessels with few endoleaks or branch occlusions.

PMID- 24093311
TI  - Commentary: chimneys are smoking hot: midterm results of the chimney technique in
      the repair of pararenal and thoracoabdominal aneurysms.

PMID- 24093312
TI  - Endovascular treatment of delayed rupture following prior abdominal aortic
      aneurysm repair achieves better survival rates.
AB  - PURPOSE: To test the hypothesis that endovascular treatment of delayed aneurysm
      rupture achieves significantly better survival rates compared to surgical
      conversion. METHODS: All patients sustaining delayed rupture following prior
      exclusion of an abdominal aortic aneurysm (AAA) either by endovascular aneurysm
      repair (EVAR) or open graft replacement from March 1995 through December 2011
      were retrieved from a prospectively maintained database at a tertiary care
      university hospital. During the study period, 35 patients (32 men; mean age 72.9
      years) presented with delayed rupture at a median 2.4 years (interquartile range
      1.3-4.3) after initial AAA repair by EVAR (n=22) or open surgery (n=13). Causes
      of post-EVAR rupture were graft-related endoleaks, while ruptures after open
      repair occurred at anastomotic suture sites. Patients were divided into groups
      regarding type of treatment for delayed rupture: 20/35 (57%) underwent successful
      EVAR (10 redo procedures), 13/35 (37%) had surgery (3 redo procedures), and 2/35
      (6%) patients received comfort care only. The primary endpoint was 30-day
      mortality. RESULTS: The 30-day mortality after curative treatment was 25% (5/20)
      for endovascular treatment compared to 54% (7/13) for surgery (p=0.14). Including
      additional deaths beyond 30 days, the overall in-hospital mortality was 52%
      (17/33). The Kaplan-Meier survival estimate for patients undergoing endovascular
      treatment was significantly higher (p=0.011). CONCLUSION: Endovascular treatment
      of delayed rupture is feasible and helps to reduce mortality. Our data suggest
      that endovascular procedures are a superior treatment option for EVAR-suitable
      patients with delayed rupture compared with surgical conversion.

PMID- 24093313
TI  - Commentary: aneurysm rupture after prior AAA repair: endovascular management of
      the ultimate failure.

PMID- 24093314
TI  - Endovascular aortic aneurysm repair in patients with hostile neck anatomy.
AB  - PURPOSE: To report a systematic review and meta-analysis of outcomes following
      endovascular aneurysm repair (EVAR) in patients with hostile neck anatomy (HNA)
      vs. those with favorable neck anatomy (FNA). METHODS: Systematic review and meta
      analysis of data on EVAR in patients with HNA and FNA was performed by 2
      reviewers in February 2013. An eligible study was required to have at least 50
      participants and to incorporate one or more of the HNA criteria of neck length
      <15 mm, neck diameter >28 mm, and/or angulation >60 degrees . Of the 24 full
      length articles ultimately reviewed, 8 were excluded, resulting in 16 articles
      that were suitable for inclusion in the meta-analysis. The study size ranged from
      55 to 5183 participants, with a total of 8920 patients in the FNA group and 3039
      patients in the HNA group. Mean follow-up ranged from 9 to 49 months. RESULTS:
      Analysis of the pooled data revealed a significant increase in 30-day mortality
      (2.4% FNA vs. 3.5% HNA; OR 1.60, 95% CI 1.13 to 2.27; p<0.01), intraoperative
      adjuncts (8.8% FNA vs. 15.4% HNA; OR 1.88, 95% CI 1.15 to 3.07; p=0.01), and 30
      day migration (0.9% FNA vs. 1.6% HNA; OR 2.08, 95% CI 1.20 to 3.62; p=0.009) in
      patients with HNA. A decrease in primary technical success (97.5% FNA vs. 93.8%
      HNA; OR 0.41, 95% CI 0.18 to 0.93; p=0.03) was significant when all 3 criteria
      were used to define HNA. For outcomes at >30 days, the increase in secondary
      interventions (OR 1.29, 95% CI 1.00 to 1.66; p=0.05) approached significance, but
      aneurysm-related mortality, all-cause mortality, migration, and aortic rupture
      did not achieve statistical significance. There was no difference in rates of sac
      expansion. Analysis of endoleak rates revealed a significant increase in 30-day
      type I endoleaks (OR 2.92, 95% CI 1.61 to 5.30; p<0.001) and late type I
      endoleaks (OR 1.71, 95% CI 1.31 to 2.23; p<0.0001) in patients with HNA.
      CONCLUSION: These results suggest that performing EVAR in patients with HNA
      increases the technical difficulty and results in poorer short-term outcomes. The
      higher rates of early and late type I endoleaks, along with secondary
      interventions, suggest that increased monitoring should be performed in this
      category of patient to ensure rapid treatment.

PMID- 24093315
TI  - A novel cautery instrument for on-site fenestration of aortic stent-grafts: a
      feasibility study of 18 patients.
AB  - PURPOSE: To report the bench-top evaluation and initial clinical use of an
      instrument for on-site fenestration of aortic stent-grafts. METHODS: A stainless
      steel thermal cautery instrument was designed to create circular stent-graft
      fenestrations from 3 to 10 mm in diameter. Three operators independently bench
      tested the instrument on thoracic stent-graft samples to evaluate size, shape,
      location, and quality of fenestrations created. For clinical use, on-site
      fenestration was performed 2 days before the endovascular procedure in a sterile
      room without access to supplemental oxygen. A fenestrator 1 or 2 mm smaller in
      diameter than the target vessel was used; the edges of the fenestrations were
      strengthened using flexible radiopaque nitinol wire. The aortic stent-graft was
      then re-sheathed and sterilized for added safety. Eighteen patients (17 men; mean
      age 51 years, range 18-80) with a variety of thoracic and juxtarenal pathologies
      were treated using Zenith TX2, Valiant Captivia, Zenith AAA, and Endurant stent
      grafts modified in this manner. RESULTS: After successful bench testing, the
      instrument was used to create 34 fenestrations in aortic stent-grafts deployed in
      the 18 patients. Size and location of fenestrations obtained were as desired.
      Subsequent catheterization of the fenestration/target vessel and covered stent
      deployment were successfully achieved in 31 (91%) fenestrations; 2 fenestrations
      had type III endoleaks and 1 fenestration was unused. There was no perioperative
      mortality, stroke, embolization, vessel dissection, renal failure, or graft
      infection. Follow-up to 1 year in the majority of patients has revealed no new
      fenestration-related problems. CONCLUSION: This simple-to-use instrument makes on
      site creation of aortic stent-graft fenestrations easy, accurate, and precise.
      The instrument is inexpensive, robust, and easily sterilized.

PMID- 24093316
TI  - Transaortic modification of the Viabahn open revascularization technique (VORTEC)
      to facilitate renal artery revascularization in a hybrid EVAR procedure.
AB  - PURPOSE: To present a modification of the Viabahn open revascularization
      technique (VORTEC) to facilitate right renal artery (RRA) revascularization via a
      limited thoracotomy and transaortic sheath during endovascular aneurysm repair
      (EVAR). CASE REPORT: A 51-year-old man with uncontrolled hypertension and limited
      respiratory reserve presented with a pararenal abdominal aortic aneurysm (AAA)
      measuring ~15*8.5*8 cm extending into the iliac arteries. Via a limited low
      thoracoabdominal incision and retroperitoneal approach, 3 of the renovisceral
      branches were exposed, but there was difficulty in approaching the RRA. A
      handmade 4-branched polytetrafluoroethylene graft (PTFE) was anastomosed to the
      descending thoracic aorta, and the 3 exposed renovisceral branches were bypassed
      sequentially. A modification of the VORTEC with a transaortic approach to
      revascularize the RRA was successful; a 7-mm*10-cm Viabahn stent-graft was
      advanced into the RRA and deployed into the RRA limb of the PTFE graft. The
      Viabahn-PTFE graft junction was fixed with interrupted suture, and its
      transaortic portion was dilated with a 7-mm balloon. EVAR was then accomplished
      with a 28.5-mm Excluder stent-graft. The final angiogram documented patent bypass
      grafts and no endoleak. Follow-up imaging showed a satisfactory stent-graft and
      patent PTFE graft without undue kinking of the Viabahn or stenosis within its
      transaortic portion. The patient remained well after 1-year follow-up.
      CONCLUSION: This transaortic modification may be a useful option for hybrid EVAR
      and application of a sutureless telescoping anastomosis technique.

PMID- 24093317
TI  - Commentary: another innovative and useful modification for the VORTEC toolbox.

PMID- 24093318
TI  - Inguinal field block for femoral artery exposure during endovascular aneurysm
      repair.
AB  - PURPOSE: To analyze the feasibility and outcomes of an inguinal field block (IFB)
      for femoral artery exposure in patients undergoing elective endovascular aneurysm
      repair (EVAR). METHODS: Between January 2004 and June 2012, 784 patients (597
      men; mean age 76 years) underwent elective EVAR via surgical cutdown to the
      common femoral arteries. The data from these procedures were retrospectively
      analyzed to determine the technical feasibility of IFB, need for conversion to
      general anesthesia, mortality, and complication rate. RESULTS: IFB was
      successfully performed in 768 (97.9%) patients. Conversion from IFB to general
      anesthesia was necessary in 11 (1.4%) patients owing to patient discomfort (n=3,
      0.4%), anxiety (n=5, 0.6%), and persistent patient movement (n=3, 0.4%). The
      remaining 5 (0.7%) patients underwent EVAR under general anesthesia because they
      refused IFB. Technical success of EVAR was 99.7%; the mean operation time was 84
      minutes and the radiation time was 13 minutes. The mean hospital stay was 3.7
      days; no patient required intensive care. At 6 months, there were no reports of
      local/systemic complications related to IFB, such as infection, seroma, hematoma,
      nerve injury, or allergic/toxic reactions. CONCLUSION: Our study demonstrated
      that performing EVAR with femoral cutdown under IFB is a feasible, safe, and
      effective surgical and anesthetic combination, with very little need for
      conversion to general anesthesia.

PMID- 24093319
TI  - Endovascular abdominal aneurysm repair and impact of systematic preoperative
      embolization of collateral arteries: endoleak analysis and long-term follow-up.
AB  - PURPOSE: To report our results of endovascular aneurysm repair (EVAR) over a 10
      year period using systematic preoperative collateral artery embolization.
      METHODS: From 1999 until 2009, 124 patients (117 men; mean age 70.8 years) with
      abdominal aortic aneurysm (AAA) underwent embolization of patent lumbar and/or
      inferior mesenteric arteries prior to elective EVAR procedures. Embolization was
      systematically attempted and, whenever possible, performed using microcoils and a
      coaxial technique. Follow-up included computed tomography and/or magnetic
      resonance imaging and abdominal radiography. RESULTS: The technical success for
      EVAR was 96% (119/124), with 4 patients dying within 30 days (3.2% perioperative
      mortality) and 1 type III endoleak accounting for the failures. Collateral
      arteries were occluded spontaneously or by embolization in 60 (48%) of 124
      patients. The endoleak rate was 50.9% (74 in 61 patients), most of which were
      type II (19%). Over a mean clinical follow-up of 60.5+/-34.1 months (range 1
      144), aneurysm sac dimensions decreased in 66 patients, increased in 19 patients,
      and were stable in 35. The endoleak rate was significantly higher in the patients
      with increasing sac diameter (p<0.001). Among the patients with patent collateral
      arteries, 38/64 (59.3%) developed 46 leaks, while 28 leaks appeared in 23 (41%)
      of 56 patients with collateral artery occlusion (p=0.069). The type II endoleak
      rate significantly differed between these two groups (47.8% vs. 3.6%, p<0.001).
      CONCLUSION: Preoperative collateral embolization seems to be a valid method of
      reducing the incidence of type II endoleak, improving the long-term outcome.

PMID- 24093320
TI  - Anatomical suitability of the T-branch stent-graft in patients with
      thoracoabdominal aortic aneurysms treated using custom-made multibranched
      endografts.
AB  - PURPOSE: To assess the anatomical suitability of the new off-the-shelf
      multibranched endograft (t-branch) in patients with thoracoabdominal aortic
      aneurysms (TAAA) previously treated by means of custom-made multibranched
      endografts. METHODS: Clinical and radiological data of 43 consecutive patients
      (34 men; mean age 72 years) with Crawford types I (n=1), II (n=16), III (n=18),
      or IV (n=8) TAAAs treated with custom-made multibranched endografts between June
      2008 and February 2013 were retrospectively reviewed. Primary anatomical
      suitability of the t-branch device was assessed using 3-dimensional computed
      tomographic angiograms. Assisted suitability referred to the ability to use
      adjuvant procedures to eliminate anatomical obstacles that did not hinder the
      custom-made devices. RESULTS: Among the study group, 21 (49%) patients were
      suitable for treatment using the t-branch device. Another 6 (14%) would have been
      suitable with the assistance of additional maneuvers, such as thoracic
      endografting with (n=3) or without (n=3) left carotid-subclavian bypass. Sixteen
      (37%) patients violated the eligibility criteria due to a distance >56 cm between
      the celiac trunk and the most caudal renal artery (9, 60%), insufficient diameter
      (<25 mm) at the level of the visceral arteries (5, 33%), upward orientation of a
      renal artery (3, 20%), inadequate (>40 mm) proximal landing zone (2, 13%), and a
      distance <67 mm between the most caudal renal artery and aortic bifurcation (1,
      7%). CONCLUSION: The t-branch stent-graft system would have been primarily
      suitable for implantation in half of the patients. With additional maneuvers, the
      assisted suitability reached 63%. Further optimization and refinement of the
      device will probably lead to a shift toward off-the-shelf multibranched stent
      graft exclusion of TAAAs.

PMID- 24093321
TI  - Evidence-based medicine in vascular and endovascular practice.

PMID- 24093322
TI  - Inflammatory mediators and cerebral embolism in carotid stenting: new markers of
      risk.
AB  - PURPOSE: To investigate serological predictors of risk for cerebral embolism
      after carotid artery stenting (CAS). METHODS: Twenty consecutive symptomatic and
      asymptomatic patients (13 men; mean age 74 years) with carotid artery stenosis
      undergoing standardized filter-protected CAS (Wallstent) were preoperatively
      evaluated to identify unstable plaque (duplex ultrasound), complicated aortic
      plaque (transesophageal echocardiography), and inflammatory status [high
      sensitivity C-reactive protein (hs-CRP) and serum amyloid-A protein (SAA) serum
      levels]. Aortic arch type, carotid tortuosity, and complexity of the procedure
      were considered. Cerebral embolism was evaluated by comparing the number, volume,
      and side (ipsilateral and non-ipsilateral) of preoperative and postoperative
      cerebral lesions detected on diffusion-weighted resonance magnetic imaging (DW
      MRI) and through light and scanning electron microscopy analysis of cerebral
      protection filters obtained from CAS. RESULTS: All CAS procedures were completed
      with no complications. All patients had a negative preoperative DW-MRI, but at
      least 1 asymptomatic cerebral lesion appeared on DW-MRI after the procedure in 18
      (90%) patients. Female gender was associated with a higher number of cerebral
      lesions (18.2+/-10.9 vs. 8.3+/-8.8 for men, p=0.03). Carotid plaque morphology,
      supra-aortic vessel anatomy, and procedure complexity did not correlate with
      number or volume of new cerebral lesions. Complicated aortic plaque was
      associated with a higher volume of non-ipsilateral cerebral lesions than
      uncomplicated plaque (235.0+/-259.3 vs. 63.6+/-63.2 mm(3), respectively; p=0.02).
      Hs-CRP >=5 mg/L and SAA >=10 mg/L were significantly associated with a higher
      number of new cerebral lesions [16.2+/-10.7 vs. 4.3+/-3.4 for hs-CRP <5 mg/L
      (p=0.02) and 14.8+/-10.3 vs. 2.8+/-3.4 for SAA <10 mg/L (p=0.006), respectively].
      Hs-CRP >=5 mg/L and SAA >=10 mg/L also correlated with greater surface
      involvement by embolic materials in the protection filters at microscopic
      analysis [37.0% (5.1%) vs. 26.9% (2.5%) for hs-CRP <5 mg/L, p=0.004; 35.9%
      (13.5%) vs. 22.2% (6.9%) for SAA <10 mg/L, p=0.02]. CONCLUSION: In addition to
      female gender and the presence of complicated aortic plaque, inflammatory status
      can be a predictor of cerebral embolism in CAS.

PMID- 24093323
TI  - Commentary: the search for reliable markers for increased carotid artery stenting
      induced cerebral embolism.

PMID- 24093324
TI  - Twelve-month results of a randomized trial comparing mono with dual antiplatelet
      therapy in endovascularly treated patients with peripheral artery disease.
AB  - PURPOSE: To present the 12-month results of a trial investigating the effects of
      dual antiplatelet therapy on target lesion revascularization (TLR) after balloon
      angioplasty +/- stenting in the femoropopliteal segment. METHODS: A prospective,
      randomized, single-center, double-blinded and placebo-controlled clinical trial
      randomly assigned 40 patients to receive pre- and postinterventional therapy with
      aspirin and clopidogrel. Another 40 patients received the same doses of aspirin
      and placebo instead of clopidogrel. Clopidogrel and placebo were stopped after 6
      months, and patients remained on aspirin only. At 12 months after the
      intervention, 36 clopidogrel patients and 37 placebo patients were reevaluated.
      RESULTS: At 6 months, clopidogrel patients had significantly lower rates of TLR
      compared to placebo patients [2 (5%) vs. 8 (20%), p=0.04]. After stopping
      clopidogrel/placebo after 6 months, there was no significant difference in TLR at
      12 months after treatment [9 (25%) clopidogrel vs. 12 (32.4%) placebo, p=0.35].
      Mortality was 0 vs. 1 in the placebo group at 6 months (p=0.32) and 0 vs. 3 at 12
      months (p=0.08). CONCLUSION: In contrast to the first report of a reduction in
      the TLR at 6 months, this advantage of dual antiplatelet therapy does not persist
      after stopping clopidogrel. Prolonged dual therapy (>6 months) should be
      considered in patients who are at high risk for restenosis.

PMID- 24093325
TI  - Clinically-driven need for secondary interventions after endovascular
      revascularization of tibial arteries in patients with critical limb ischemia.
AB  - PURPOSE: To assess the need for clinically-driven secondary revascularization in
      critical limb ischemia (CLI) patients subsequent to tibial angioplasty during a 2
      year follow-up. METHODS: Between 2008 and 2010, a total of 128 consecutive CLI
      patients (80 men; mean age 76.5+/-9.8 years) underwent tibial angioplasty in 139
      limbs. Rutherford categories, ankle-brachial index measurements, and lower limb
      oscillometries were prospectively assessed. All patients were followed at 3, 6,
      12 months, and annually thereafter. Rates of death, primary and secondary
      sustained clinical improvement, target lesion (TLR) and target extremity
      revascularization (TER), as well as major amputation, were analyzed
      retrospectively. Primary clinical improvement was defined as improvement in
      Rutherford category to a level of intermittent claudication without unplanned
      amputation or TLR. RESULTS: All-cause mortality was 8.6%, 14.8%, 22.9%, and 29.1%
      at 3, 6, 12, and 24 months. At the same intervals, rates of primary sustained
      clinical improvement were 74.5%, 53.0%, 42.7%, and 37.1%; for secondary
      improvement, the rates were 89.1%, 76.0%, 68.4%, and 65.0%. Clinically-driven TLR
      rates were 14.6%, 29.1%, 41.6%, 46.2%; the rates for TER were 3.0%, 13.6%, 17.2%,
      and 27.6% in corresponding intervals, while the rates of major amputation were
      1.5%, 5.5%, 10.1%, and 10.1%. CONCLUSION: Clinically-driven TLR is frequently
      required to maintain favorable functional clinical outcomes in CLI patients
      following tibial angioplasty. Dedicated technologies addressing tibial arterial
      restenosis warrant further academic scrutiny.

PMID- 24093326
TI  - Stent-graft implantation to treat an inferior vena cava aneurysm.
AB  - PURPOSE: To present a patient with a primary inferior vena cava aneurysm who was
      subjected to endovascular treatment. CASE REPORT: A 60-year-old man, suffering
      from pulmonary embolism, was diagnosed with a vena cava aneurysm located below
      the renal veins. Through the right common femoral vein, a custom-made stent-graft
      was implanted. Proximal and distal barbs were incorporated in the frame to assist
      fixation and avoid caudal or cephalad migration. The procedure was performed
      without any technical or clinical complications, and the aneurysm was completely
      excluded from the circulation. During the 6-month follow-up, imaging verified the
      correct position of the stent-graft and exclusion of the aneurysm without
      endoleak or any other complication. CONCLUSION: In patients with inferior vena
      cava aneurysm, stent-graft implantation may be an alternative to open surgery.

PMID- 24093328
TI  - Crystal structure and transport in merged InAs nanowires MBE grown on (001) InAs.
AB  - Molecular beam epitaxy growth of merging InAs nanowire intersections, that is, a
      first step toward the realization of a network of such nanowires, is reported.
      While InAs nanowires play already a leading role in the search for Majorana
      fermions, a network of these nanowires is expected to promote their exchange and
      allow for further development of this field. The structural properties of merged
      InAs nanowire intersections have been investigated using scanning and
      transmission electron microscope imaging. At the heart of the intersection, a
      sharp change of the crystal structure from wurtzite to perfect zinc blende is
      observed. The performed low-temperature conductance measurements demonstrate that
      the intersection does not impose an obstacle to current transport. 

PMID- 24093329
TI  - Generation and characterization of a Leishmania tarentolae strain for site
      directed in vivo biotinylation of recombinant proteins.
AB  - Leishmania tarentolae is a non-human-pathogenic Leishmania species of growing
      interest in biotechnology, as it is well-suited for the expression of human
      recombinant proteins. For many applications it is desirable to express
      recombinant proteins with a tag allowing easy purification and detection. Hence,
      we adopted a scheme to express recombinant proteins with a His6-tag and,
      additionally, to site-specifically in vivo biotinylate them for detection.
      Biotinylation is a relatively rare modification of endogenous proteins that
      allows easy detection with negligible cross-reactivity. Here, we established a
      genetically engineered L. tarentolae strain constitutively expressing the codon
      optimized biotin-protein ligase from Escherichia coli (BirA). We thoroughly
      analyzed the strain for functionality using 2-D polyacrylamide-gel
      electrophoresis (PAGE), mass spectrometry, and transmission electron microscopy
      (TEM). We could demonstrate that neither metabolic changes (growth rate) nor
      structural abnormalities (TEM) occurred. To our knowledge, we show the first 2-D
      PAGE analyses of L. tarentolae. Our results demonstrate the great benefit of the
      established L. tarentolae in vivo biotinylation strain for production of dual
      tagged recombinant proteins. Additionally, 2-D PAGE and TEM results give insights
      into the biology of L. tarentolae, helping to better understand Leishmania
      species. Finally, we envisage that the system is transferable to human-pathogenic
      species. 

PMID- 24093330
TI  - Conformational dynamics of a regulator of G-protein signaling protein reveals a
      mechanism of allosteric inhibition by a small molecule.
AB  - Regulators of G protein signaling (RGS) proteins are key players in regulating
      signaling via G protein-coupled receptors. RGS proteins directly bind to the
      Galpha-subunits of activated heterotrimeric G-proteins, and accelerate the rate
      of GTP hydrolysis, thereby rapidly deactivating G-proteins. Using atomistic
      simulations and NMR spectroscopy, we have studied in molecular detail the
      mechanism of action of CCG-50014, a potent small molecule inhibitor of RGS4 that
      covalently binds to cysteine residues on RGS4. We apply temperature-accelerated
      molecular dynamics (TAMD) to carry out enhanced conformational sampling of apo
      RGS4 structures, and consistently find that the alpha5-alpha6 helix pair of RGS4
      can spontaneously span open-like conformations, allowing binding of CCG-50014 to
      the buried side-chain of Cys95. Both NMR experiments and MD simulations reveal
      chemical shift perturbations in residues in the vicinity of inhibitor binding
      site as well as in the RGS4-Galpha binding interface. Consistent with a loss of G
      protein binding, GAP activity, and allosteric mechanism of action of CCG-50014,
      our simulations of the RGS4-Galpha complex in the presence of inhibitor suggest a
      relatively unstable protein-protein interaction. These results have potential
      implications for understanding how the conformational dynamics among RGS proteins
      may play a key role in the sensitivity of inhibitors. 

PMID- 24093331
TI  - A new lipid-rich microalga Scenedesmus sp. strain R-16 isolated using Nile red
      staining: effects of carbon and nitrogen sources and initial pH on the biomass
      and lipid production.
AB  - BACKGROUND: Biodiesel production from oleaginous microalgae shows great potential
      as a promising alternative to conventional fossil fuels. Currently, most research
      focus on algal biomass production with autotrophic cultivation, but this
      cultivation strategy induces low biomass concentration and it is difficult to be
      used in large-scale algal biomass production. By contrast, heterotrophic algae
      allows higher growth rate and can accumulate higher lipid. However, the fast
      growing and lipid-rich microalgae that can be cultivated in heterotrophic system
      for the industrial application of biodiesel production are still few. Traditional
      solvent extraction and gravimetric determination to detect the microalgal total
      lipid content is time-consuming and laborious, which has become a major limiting
      factor for selecting large number of algae specimens. Thus, it is critical to
      develop a rapid and efficient procedure for the screening of lipid-rich
      microalgae. RESULTS: A novel green microalga Scenedesmus sp. strain R-16 with
      high total lipid content was selected using the Nile red staining from eighty
      eight isolates. Various carbon sources (fructose, glucose and acetate) and
      nitrogen sources (nitrate, urea, peptone and yeast extract) can be utilized for
      microalgal growth and lipid production, and the optimal carbon and nitrogen
      sources were glucose (10 g L-1) and nitrate (0.6 g L-1), respectively. Compared
      to autotrophic situation, the strain R-16 can grow well heterotrophically without
      light and the accumulated total lipid content and biomass reached 43.4% and 3.46
      g L-1, respectively. In addition, nitrogen deficiency led to an accumulation of
      lipid and the total lipid content was as high as 52.6%, and it was worth noting
      that strain R-16 exhibited strong tolerance to high glucose (up to 100 g L-1) and
      a wide range of pH (4.0-11.0). CONCLUSIONS: The newly developed ultrasonic
      assisted Nile red method proved to be an efficient isolation procedure and was
      successfully used in the selection of oleaginous microalgae. The isolated novel
      green microalgal strain R-16 was rich in lipid and can live in varied and
      contrasting conditions. The algae appeared to have great potential for
      application in microalgae-based biodiesel production.

PMID- 24093332
TI  - The red ear syndrome.
AB  - Red Ear Syndrome (RES) is a very rare disorder, with approximately 100 published
      cases in the medical literature. Red ear (RE) episodes are characterised by
      unilateral or bilateral attacks of paroxysmal burning sensations and reddening of
      the external ear. The duration of these episodes ranges from a few seconds to
      several hours. The attacks occur with a frequency ranging from several a day to a
      few per year. Episodes can occur spontaneously or be triggered, most frequently
      by rubbing or touching the ear, heat or cold, chewing, brushing of the hair, neck
      movements or exertion. Early-onset idiopathic RES seems to be associated with
      migraine, whereas late-onset idiopathic forms have been reported in association
      with trigeminal autonomic cephalalgias (TACs). Secondary forms of RES occur with
      upper cervical spine disorders or temporo-mandibular joint dysfunction. RES is
      regarded refractory to medical treatments, although some migraine preventative
      treatments have shown moderate benefit mainly in patients with migraine-related
      attacks. The pathophysiology of RES is still unclear but several hypotheses
      involving peripheral or central nervous system mechanisms have been proposed. 

PMID- 24093333
TI  - Diastereodifferentiating photocyclodimerization of 2-anthracenecarboxylates
      tethered to a cyclic tetrasaccharide scaffold: critical control of
      photoreactivity and stereoselectivity.
AB  - From a complex mixture of mono- and di-2-anthracenecarboxylic acid (AC) esters of
      cyclic nigerosylnigerose (CNN), two monoesters (2(B) and 6(A)) and four diesters
      in which AC was introduced on the transannular B/D (2(B)2(D)), adjacent A/B and
      A/D (6(A)2(B) and 6(A)2(D)), and same B/B (2(B)3(B)) nigerose rings were
      isolated. Possessing two ACs at distant positions, 2(B)2(D) and 6(A)2(D) showed
      negative Cotton effects for the (1)Bb band, the intensities of which were
      stronger than that of 6(A). 2(B)2(D) and 6(A)2(D) slowly photocyclodimerized to
      give HH dimers 3* and 4 with 57% and 81% HH selectivity, respectively, which were
      appreciably higher than that for 6(A) (34%), while the enantiomeric excesses
      (ee's) of anti-HH dimer 3* were 2% and -18%, respectively. In contrast, 6(A)2(B)
      and 2(B)3(B) carrying two ACs on adjacent A and B rings or at vicinal positions
      on the B ring, respectively, exhibited strong positive CD couplets, the
      amplitudes of which amounted to 97 and 409 M(-1) cm(-1), respectively. Upon
      irradiation, 6(A)2(B) afforded 3* with -62% ee and 4 in 96% combined yield,
      whereas 2(B)3(B) gave almost exclusively 3* with -99% ee in 96% yield, likely as
      a result of the introduction of two ACs at the vicinal positions of the rigid CNN
      scaffold. 

PMID- 24093335
TI  - Structure and other molecular properties of actinide trichlorides AnCl3 (An = Th
      Cm).
AB  - The ground-state molecular properties of the trichlorides of light actinides (An
      = Th-Cm) have been predicted by state-of-the-art quantum chemical calculations.
      The ground electronic states have been determined by multireference calculations
      at the CASPT2 level including both scalar and spin-orbit relativistic effects.
      These studies supported the expected single-configuration character of ThCl3 and
      CmCl3 with their well-defined 6dsigma/7s hybrid and 5f(7) configurations,
      respectively. In contrast, the intermediate actinides (PaCl3-AmCl3) with partly
      filled 5f shells have numerous very low-lying excited states and consequently a
      mixed character of the spin-orbit ground states. Apart from the planar ThCl3 the
      ground-state molecular geometries proved to be pyramidal with C(3v) symmetry. The
      gradually decreasing An-Cl bond distances reveal the actinide contraction known
      for the atomic and ionic radii of these actinide atoms. Other ground-state
      molecular properties as vibrational frequencies and natural charges have been
      obtained by density functional theory calculations using the B3LYP exchange
      correlation functional in conjunction with small-core relativistic energy
      consistent pseudopotentials for the actinides.

PMID- 24093334
TI  - Obesity prevalence and unfavorable health risk behaviors among German
      kindergarten teachers: cross-sectional results of the kindergarten teacher health
      study.
AB  - BACKGROUND: The aim of the study was to investigate obesity status and associated
      health risk behaviors in a sample of German kindergarten teachers. At present,
      such data are not available, despite the fact that kindergarten teachers educate
      children at a formative time in their lives. METHODS: Kindergarten teachers aged
      18-62 years (n = 313) were invited to participate in the Kindergarten Teacher
      Health Study (KTHS) by completing a self-reported questionnaire. We analyzed
      their obesity status, health risk behaviors (i.e., habitual physical activity,
      screen time activities, eating behavior patterns, smoking), and their general
      ability to identify overweight children and the associated health risks of
      overweight and obesity based on special age- and sex-specific silhouettes. After
      adjusting for covariates, bivariate correlations were conducted for associations
      between body mass index (BMI) and health risk behaviors, while analyses of
      variance (ANOVAs) were used to analyze differences of health risk behaviors
      between BMI groups. Logistic regression analyses were conducted to predict
      determinants of kindergarten teachers who did not correctly identify the
      overweight silhouettes and their associated physical and mental health risks.
      Additionally, data regarding kindergarten teachers' weight status and smoking
      behavior were compared with nationally representative data from the 2009
      Microcensus (n = 371310) using the Mann-Whitney U-test. RESULTS: The prevalence
      rates of overweight and obesity were 41.2% and 17.9%, respectively. The
      prevalence of obesity was significantly higher in kindergarten teachers (p <
      0.001) compared to national Microcensus data. Only 44.6% of teachers were able to
      identify overweight children correctly. The fact that being overweight is
      associated with physical and mental health risks was only reported by 40.1% and
      21.2% of teachers, respectively. Older kindergarten teachers were more likely to
      misclassify the overweight silhouettes, while younger, normal-weight, and
      overweight kindergarten teachers were more likely to underestimate the associated
      health risks. Obese kindergarten teachers reported spending more time in front of
      computer and television screens than their normal-weight counterparts, especially
      on weekends. In addition, obese kindergarten teachers reported eating less often
      with their families and more frequently reported watching television during
      meals. CONCLUSIONS: Advanced monitoring and multifaceted interventions to improve
      the health behaviors of kindergarten teachers should be given high priority.
      Because kindergarten teachers' behavioral modeling presumably mediates children's
      health behaviors, additional research is needed about kindergarten teachers'
      health and its proposed interaction with children's health.

PMID- 24093337
TI  - Note from the editor.

PMID- 24093338
TI  - Helping tomorrow's health care consumers.

PMID- 24093336
TI  - Validation of the new classification of pauci-immune glomerulonephritis in a
      United States cohort and its correlation with renal outcome.
AB  - BACKGROUND: Renal biopsies provide important diagnostic and prognostic
      information in ANCA associated glomerulonephritis. A new classification for
      prognostication of pauci-immune glomerulonephritis (GN) based on four categories
      (Mixed, Crescentic, Sclerotic and Focal) was proposed by an international working
      group of renal pathologists (IWGRP). The goal of our study was to apply the
      proposed classification system to a United States cohort of vasculitis patients
      and determine the association of IWGRP class with estimated glomerular filtration
      rate (eGFR) at one year. METHODS: Seventy-six cases of pauci-immune
      glomerulonephritis diagnosed from 1995 to 2011 from a single center were
      identified for this retrospective study. Clinical data were collected by
      abstraction from medical records. Histology was reviewed by a pathologist and
      classified according to the new classification. MDRD formula was used to
      calculate eGFR. We correlated IWGRP class to renal function at presentation and
      at one year. *2, ANOVA, and linear regression analysis were performed as
      appropriate. RESULTS: Renal biopsies were categorized as focal: n = 20,
      crescentic: n = 18, mixed: n = 27, sclerotic: n = 11. The baseline e-GFR was
      lowest in the crescentic class and highest in the focal class. In linear
      regression analysis investigating e-GFR at 1 year; age and baseline e-GFR were
      independent predictors of e-GFR at 1 year. CONCLUSIONS: The e-GFR at diagnosis
      and age were predictors of e-GFR at 1 year. Pathologic class at diagnosis may
      also be a helpful tool in risk stratification at diagnosis.

PMID- 24093339
TI  - The progress and promise of health literacy research.

PMID- 24093340
TI  - Recommendations for advancing health literacy measurement.
AB  - Health literacy has become a national priority in the United States. Although
      less is known about the rate, outcomes, and costs associated with health literacy
      globally relative to the United States, the subject has received increasing
      attention internationally as well. Definitions, conceptual models, and health
      literacy measures have proliferated in recent years, and consensus does not exist
      regarding which of these to use. This article offers the following 5
      recommendations for setting a research agenda to advance the science of health
      literacy measurement: (a) develop a comprehensive unified conceptual framework,
      (b) leverage the measurement knowledge the field has gained thus far, (c)
      empirically test frameworks and measures using robust research methods, (d) use a
      tiered approach to measuring health literacy, and (e) advocate for ongoing
      research and dissemination. These recommendations seek to ensure clarity, rigor,
      and transparency as part of a systematic approach to health literacy measurement.
      Once these steps are taken, the field of health literacy can move forward more
      effectively. 

PMID- 24093341
TI  - The need for trauma-sensitive language use in literacy and health literacy
      screening instruments.
AB  - The authors recently began a research study, funded by the National Institute of
      Mental Health, aimed at increasing the understanding of the ways in which limited
      literacy affects the lives of people with serious mental illness. In preparing
      for the study, the authors reviewed many health literacy screens and assessments
      for their appropriateness in public urban mental health settings. The Rapid
      Estimate of Adult Literacy in Medicine and the Test of Functional Health Literacy
      in Adults, perhaps the most frequently used assessments of health literacy,
      involve assessments that include lists of words that the test-taker must choose
      from or read. Each of these instruments includes language that is potentially
      triggering for trauma survivors, particularly those with posttraumatic stress
      disorder (PTSD). The research participants for the current project are consumers
      of mental health services, and thus, the authors believe it is essential to
      remove the problematic language, given that the likelihood of a diagnosis of PTSD
      and/or a history of abuse is higher than average among this population. However,
      the authors argue that this issue applies to anyone who administers these
      instruments, because sexual assault and abuse, as well as PTSD diagnoses, are
      certainly not confined to those who seek mental health services. The authors' aim
      is not only to call attention to the use of triggering language in existing
      literacy and health-related assessments and research instruments, but also to
      advocate that others take similar steps toward embracing more sensitive language
      by removing or replacing words that may cause unnecessary stress, anxiety, or
      pain to those who are at increased risk of retraumatization. 

PMID- 24093342
TI  - Rethinking adherence: a health literacy-informed model of medication self
      management.
AB  - Medication adherence has received a great deal of attention over the past several
      decades; however, its definition and measurement remain elusive. The authors
      propose a new definition of medication self-management that is guided by evidence
      from the field of health literacy. Specifically, a new conceptual model is
      introduced that deconstructs the tasks associated with taking prescription drugs;
      including the knowledge, skills and behaviors necessary for patients to correctly
      take medications and sustain use over time in ambulatory care. This model is then
      used to review and criticize current adherence measures as well as to offer
      guidance to future interventions promoting medication self-management, especially
      among patients with low literacy skills. 

PMID- 24093343
TI  - A drug by any other name: patients' ability to identify medication regimens and
      its association with adherence and health outcomes.
AB  - Understanding and organizing medication regimens can be challenging, and many
      patients struggle to properly dose prescribed medicine, potentially leading to
      less effective treatment or even harm. Generic prescriptions are increasingly
      common and may change in appearance, adding further complexity. The authors aimed
      to investigate familiarity with the drug regimen among a cohort of patients with
      diagnosed hypertension. Specifically, they determined the prevalence of patients'
      knowledge of their prescribed drug names and dosages compared to those who relied
      only on physical characteristics (size, shape, color) of their medications. The
      relationship between patients' identification strategies, self-reported
      adherence, and health outcomes (blood pressure control, hospitalization) were
      investigated. Patients who were dependent on the visual identification of their
      prescription medicine reported worse adherence. In addition, they had
      significantly lower rates of blood pressure control and greater risk of
      hospitalization. The ability to identify prescribed medicines by name may be
      helpful for screening and responding to patients at greater risk of making
      medication errors or being less engaged with their regimen for adherence
      purposes. 

PMID- 24093344
TI  - Take-Wait-Stop: a patient-centered strategy for writing PRN medication
      instructions.
AB  - Recent studies have linked patient misunderstanding of label instructions for as
      needed (PRN) medications to dosing errors. This study conducted a preliminary
      field test of patient-centered PRN label instructions. Patients participated in a
      hypothetical dosing experiment and were randomized to a patient-centered label
      (referred to as "Take-Wait-Stop") or standard label. Participants were asked to
      demonstrate dosing the medicine over 24 hours. Three types of independent dosing
      errors were measured: (a) taking more than two pills at one time, (b) exceeding
      the maximum daily dose, and (c) waiting fewer than 4 hours between doses.
      Generalized linear models were used to assess the association between label type,
      health literacy, and sociodemographic characteristics. Participants' mean age was
      39.8 years, 62.1% were female, 43.7% were White, and 72.4% had adequate literacy.
      Of participants, 31.8% who were shown the standard label demonstrated taking in
      excess of 6 pills in 24 hours compared with only 14.0% of participants who were
      shown the Take-Wait-Stop label (p = .05). Overall, only 1 person demonstrated he
      would take more than 2 pills in a single dose. Of the standard label group, 20.5%
      demonstrated dosing intervals of fewer than 4 hours compared with 23.3% of the
      Take-Wait-Stop label group (p=.75). In a multivariate model, participants who
      were exposed to the standard label were 2.5 times more likely to exceed the
      recommended maximum daily dose (95% CI [1.05, 7.70], p=.03). The Take-Wait-Stop
      label was beneficial in preventing participants from exceeding the maximum dose
      in 24 hours, although it did not significantly reduce other dosing errors.

PMID- 24093345
TI  - Development of a patient-centered bilingual prescription drug label.
AB  - Research shows that prescription drug labels are often difficult for patients to
      understand, which contributes to medication errors and nonadherence. In this
      study, the authors developed and qualitatively evaluated an evidence-based
      bilingual prescription container label designed to improve understanding. The
      authors developed several prototypes in English only or in English and Spanish.
      The labels included an image of the drug, an icon to show its purpose, and plain
      language instructions presented in a 4-time-of-day table. In 5 focus groups and
      interviews that included 57 participants, patients and pharmacists critically
      reviewed the designs and compared them with traditional medication labels and
      reformatted labels without illustrations. Patients strongly preferred labels that
      grouped patient-relevant content, highlighted key information, and included drug
      indication icons. They also preferred having the 4-time-of-day table and plain
      language text instructions as opposed to either one alone. Patients preferred
      having pertinent warnings on the main label instead of auxiliary labels.
      Pharmacists and Latino patients valued having Spanish and English instructions on
      the label, so both parties could understand the content. The final label design
      adheres to the latest national- and state-level recommendations for label format
      and incorporates additional improvements on the basis of patient and pharmacist
      input. This design may serve as a prototype for improving prescription drug
      labeling. 

PMID- 24093346
TI  - Nurse overestimation of patients' health literacy.
AB  - Patient education and effective communication are core elements of the nursing
      profession; therefore, awareness of a patient's health literacy is integral to
      patient care, safety, education, and counseling. Several past studies have
      suggested that health care providers overestimate their patient's health
      literacy. In this study, the authors compare inpatient nurses' estimate of their
      patient's health literacy to the patient's health literacy using Newest Vital
      Sign as the health literacy measurement. A total of 65 patients and 30 nurses
      were enrolled in this trial. The results demonstrate that nurses incorrectly
      identify patients with low health literacy. In addition, overestimates outnumber
      underestimates 6 to 1. The results reinforce previous evidence that health care
      providers overestimate a patient's health literacy. The overestimation of a
      patient's health literacy by nursing personnel may contribute to the widespread
      problem of poor health outcomes and hospital readmission rates. 

PMID- 24093347
TI  - Nurse practitioners' knowledge, experience, and intention to use health literacy
      strategies in clinical practice.
AB  - Nurse practitioners' (NPs) knowledge, experience, and intention to use health
      literacy strategies in practice were investigated using the Theory of Planned
      Behavior as the theoretical framework. NPs who work in outpatient settings were
      recruited at a national NP conference. Participants were administered 3 self
      report instruments: Health Literacy Knowledge and Experience Survey, Parts I and
      II; and the Health Literacy Strategies Behavioral Intention Questionnaire.
      Overall knowledge of health literacy and health literacy strategies was found to
      be low. Screening patients for low health literacy and evaluating patient
      education materials were found to be areas of knowledge deficit. Most NP
      participants used written patient education materials with alternate formats for
      patient education, such as audiotapes, videotapes, or computer software rarely
      used. Statistically significant differences were found in mean experience scores
      between NP level of educational preparation and NP practice settings. The
      intention to use health literacy strategies in practice was found to be strong.
      The findings of this investigation offer implications for enhancing NP curriculum
      and for continuing education opportunities. Increasing NPs' knowledge of health
      literacy and facilitating the use of health literacy strategies has the potential
      to change clinical practice and support improved patient outcomes. 

PMID- 24093348
TI  - Health literacy practices and educational competencies for health professionals:
      a consensus study.
AB  - Health care professionals often lack adequate knowledge about health literacy and
      the skills needed to address low health literacy among patients and their
      caregivers. Many promising practices for mitigating the effects of low health
      literacy are not used consistently. Improving health literacy training for health
      care professionals has received increasing emphasis in recent years. The
      development and evaluation of curricula for health professionals has been limited
      by the lack of agreed-upon educational competencies in this area. This study
      aimed to identify a set of health literacy educational competencies and target
      behaviors, or practices, relevant to the training of all health care
      professionals. The authors conducted a thorough literature review to identify a
      comprehensive list of potential health literacy competencies and practices, which
      they categorized into 1 or more educational domains (i.e., knowledge, skills,
      attitudes) or a practice domain. The authors stated each item in operationalized
      language following Bloom's Taxonomy. The authors then used a modified Delphi
      method to identify consensus among a group of 23 health professions education
      experts representing 11 fields in the health professions. Participants rated
      their level of agreement as to whether a competency or practice was both
      appropriate and important for all health professions students. A predetermined
      threshold of 70% agreement was used to define consensus. After 4 rounds of
      ratings and modifications, consensus agreement was reached on 62 out of 64
      potential educational competencies (24 knowledge items, 27 skill items, and 11
      attitude items), and 32 out of 33 potential practices. This study is the first
      known attempt to develop consensus on a list of health literacy practices and to
      translate recommended health literacy practices into an agreed-upon set of
      measurable educational competencies for health professionals. Further work is
      needed to prioritize the competencies and practices in terms of relative
      importance. 

PMID- 24093349
TI  - Visual causal models enhance clinical explanations of treatments for generalized
      anxiety disorder.
AB  - A daily challenge in clinical practice is to adequately explain disorders and
      treatments to patients of varying levels of literacy in a time-limited situation.
      Drawing jointly upon research on causal reasoning and multimodal theory, the
      authors asked whether adding visual causal models to clinical explanations
      promotes patient learning. Participants were 86 people currently or formerly
      diagnosed with a mood disorder and 104 lay people in Boston, Massachusetts, USA,
      who were randomly assigned to receive either a visual causal model (dual-mode)
      presentation or auditory-only presentation of an explanation about generalized
      anxiety disorder and its treatment. Participants' knowledge was tested before,
      immediately after, and 4 weeks after the presentation. Patients and lay people
      learned significantly more from visual causal model presentations than from
      auditory-only presentations, and visual causal models were perceived to be
      helpful. Participants retained some information 4 weeks after the presentation,
      although the advantage of visual causal models did not persist in the long term.
      In conclusion, dual-mode presentations featuring visual causal models yield
      significant relative gains in patient comprehension immediately after the
      clinical session, at a time when the authors suggest that patients may be most
      willing to begin the recommended treatment plan. 

PMID- 24093350
TI  - What do healthy women know about the consequences of delayed childbearing?
AB  - Female fertility declines dramatically with age, and childbearing at older
      maternal ages has significant medical consequences for mother and infant that are
      well-known to health professionals. Despite this, the average maternal age in the
      United States continues to rise. Many factors likely contribute to this secular
      trend; to date, no research has examined whether American women are aware of the
      complications of deferring conception and how this correlates with health
      literacy. The purpose of this study was to evaluate women's knowledge of the
      implications of delaying pregnancy. A structured, in-person interview was
      administered to 300 women between 20 and 50 years of age attending 1 of 2
      gynecologic clinics at a single institution. Demographic information, medical
      history, and gynecologic history were obtained; and participants answered
      questions about the implications of aging for fertility and pregnancy outcome.
      Health literacy and numeracy were assessed. Participants demonstrated knowledge
      deficits about the implications of aging on fertility and pregnancy, and many
      were unfamiliar with success rates of infertility treatments. Several demographic
      factors correlated with knowledge; health literacy and numeracy were both
      important predictive variables. To the authors' knowledge, this is the first
      study of women's knowledge about fertility, aging, and their health literacy.
      Awareness of the importance of health literacy and numeracy should inform future
      educational efforts about fertility. 

PMID- 24093351
TI  - Association of brief health literacy screening and blood pressure in primary
      care.
AB  - Health literacy impacts health outcomes. However, the relationship to blood
      pressure is inconsistent. This study aimed to determine whether health literacy,
      assessed by clinic staff, is associated with blood pressure among patients with
      hypertension. The design was a cross-sectional study of a large sample of primary
      care patient encounters in 3 academic medical center clinics in Nashville,
      Tennessee. Health literacy was assessed using the Brief Health Literacy Screen,
      with higher scores indicating higher health literacy. Blood pressure was
      extracted from the electronic health record. Using 23,483 encounters in 10,644
      patients, the authors examined the association of health literacy with blood
      pressure in multivariable analyses, adjusting for age, gender, race, education,
      and clinic location. Independent of educational attainment, 3-point increases in
      health literacy scores were associated with 0.74 mmHg higher systolic blood
      pressure (95% CI [0.38, 1.09]) and 0.30 mmHg higher diastolic blood pressure (95%
      CI [0.08, 0.51]). No interaction between education and health literacy was
      observed (p = .91). In this large primary care population of patients with
      hypertension, higher health literacy, as screened in clinical practice, was
      associated with a small increase in blood pressures. Future research is needed to
      explore this unexpected finding.

PMID- 24093353
TI  - Motivation for a health-literate health care system--does socioeconomic status
      play a substantial role? Implications for an Irish health policymaker.
AB  - In this article, the authors argue that the association between socioeconomic
      status and motivation for a health-literate health care system has implications
      for health policymakers. As Ireland now undergoes health care reform, the authors
      pose the question, "Should policymakers invest in health literacy as
      predominately a health inequalities or a public health issue?" Data from 2
      cohorts of the Survey of Lifestyle, Attitudes and Nutrition (1998 and 2002) were
      used to construct a motivation for a health-literate health care system variable.
      Multivariate logistic regressions and concentration curves were used in the
      analyses of this variable. Of the 12,513 pooled respondents, 46% sought at least
      1 attribute on a health-literate health care system. No discernible trend emerged
      from the main independent variables-social class grouping, medical card
      eligibility, level of education, and employment-in the regression analyses. The
      concentration curve, for 2002 data, graphically showed that the motivation for a
      health-literate health care system is spread equally across the income
      distribution. This analysis and more recent data suggest that health literacy in
      Ireland should be viewed predominately as a public health issue with a policy
      focus at a system level. 

PMID- 24093352
TI  - Limited health literacy and decline in executive function in older adults.
AB  - Limited health literacy is associated with worse executive function, but the
      association between limited health literacy and decline in executive function has
      not been established because of a lack of longitudinal studies. The authors aimed
      to examine this association by studying a prospective cohort in the setting of a
      randomized controlled trial to promote walking in older adults. Participants were
      community-dwelling older adults (65 years of age or older) who scored 2 or more
      on the Mini-Cog, without depression (score of less than 15 on the 9-item Patient
      Health Questionnaire), and who completed baseline and 12-month evaluations (n =
      226). Health literacy was measured using the Short Test of Functional Health
      Literacy in Adults. Executive function measured at baseline and 12 months using
      the Trail Making Test (TMT), Controlled Oral Word Association Test, and Category
      Fluency. The associations between health literacy and 12-month decline in each
      test of executive function were modeled using multivariate linear regression.
      Health literacy was found to be limited in 37% of participants. Limited health
      literacy was associated with reduced performance on all 3 executive function
      tests. In fully adjusted models, limited health literacy was associated with
      greater 12-month decline in performance on the TMT than higher health literacy (p
      = .01). In conclusion, older adults with limited health literacy are at risk for
      more rapid decline in scores on the TMT, a measure of executive function.

PMID- 24093354
TI  - The relationship between health, education, and health literacy: results from the
      Dutch Adult Literacy and Life Skills Survey.
AB  - Health literacy has been put forward as a potential mechanism explaining the well
      documented relationship between education and health. However, little empirical
      research has been undertaken to explore this hypothesis. The present study aims
      to study whether health literacy could be a pathway by which level of education
      affects health status. Health literacy was measured by the Health Activities and
      Literacy Scale, using data from a subsample of 5,136 adults between the ages of
      25 and 65 years, gathered within the context of the 2007 Dutch Adult Literacy and
      Life Skills Survey. Linear regression analyses were used in separate models to
      estimate the extent to which health literacy mediates educational disparities in
      self-reported general health, physical health status, and mental health status as
      measured by the Short Form-12. Health literacy was found to partially mediate the
      association between low education and low self-reported health status. As such,
      improving health literacy may be a useful strategy for reducing disparities in
      health related to education, as health literacy appears to play a role in
      explaining the underlying mechanism driving the relationship between low level of
      education and poor health. 

PMID- 24093355
TI  - Understanding health literacy measurement through eye tracking.
AB  - This study used eye-tracking technology to explore how individuals with different
      levels of health literacy visualize health-related information. The authors
      recruited 25 university administrative staff (more likely to have adequate health
      literacy skills) and 25 adults enrolled in an adult literacy program (more likely
      to have limited health literacy skills). The authors administered the Newest
      Vital Sign (NVS) health literacy assessment to each participant. The assessment
      involves having individuals answer questions about a nutrition label while
      viewing the label. The authors used computerized eye-tracking technology to
      measure the amount of time each participant spent fixing their view at nutrition
      label information that was relevant to the questions being asked and the amount
      of time they spent viewing nonrelevant information. Results showed that lower NVS
      scores were significantly associated with more time spent on information not
      relevant for answering the NVS items. This finding suggests that efforts to
      improve health literacy measurement should include the ability to differentiate
      not just between individuals who have difficulty interpreting and using health
      information, but also between those who have difficulty finding relevant
      information. In addition, this finding suggests that health education material
      should minimize the inclusion of nonrelevant information. 

PMID- 24093356
TI  - More than meets the eye: relationship between low health literacy and poor vision
      in hospitalized patients.
AB  - Patient-centered care includes involving patients and their families in self
      management of chronic diseases. Identifying and addressing barriers to self
      management, including those related to health literacy and vision limitations,
      may enhance one's ability to self-manage. A set of brief verbal screening
      questions (BVSQ) that does not rely on sufficient vision to assess health
      literacy was developed by Chew and colleagues in the outpatient setting. The
      authors aimed to evaluate the usefulness of this tool for hospitalized patients
      and to determine the prevalence of poor vision among inpatients. In a prospective
      study, the BVSQ and the Rapid Estimate of Adult Learning in Medicine-Revised
      (REALM-R; among participants with sufficient vision, >= 20/50 Snellen) were
      administered to general medicine inpatients. Of 893 participants, 79% were
      African American, and 57% were female; the mean age was 53 years. Among 668
      participants who completed both tools, the proportion with low health literacy
      was 38% with the BVSQ versus 47% with the REALM-R (p = .0001). Almost one fourth
      of participants had insufficient vision; participants with insufficient vision
      were more likely to be identified as having low health literacy by the BVSQ,
      compared with those with sufficient vision (59% vs. 38%, p < .001).

PMID- 24093357
TI  - Development and validation of the Chinese Health Literacy Scale for Chronic Care.
AB  - This study aims to develop and test the psychometric properties of the Chinese
      Health Literacy Scale for Chronic Care (CHLCC). This is a methodological study
      with a sample of 262 patients 65 years of age and older who had chronic
      illnesses. Pearson's correlation, independent sample t tests, and analyses of
      variance were used. The CHLCC showed a significant positive correlation with
      Chinese literacy levels (r = 0.80; p < .001) but was negatively correlated with
      age (r =-0.31; p <.001). Respondents who were male (t =4.34; p <.001) and who had
      reached Grade 12 or higher in school (F = 51.80; p <.001) had higher CHLCC scores
      than did their counterparts. Individuals with high levels of health literacy had
      fewer hospitalizations than did their counterparts (beta =-0.31; incidence rate
      ratio = 0.73; p <.05). The CHLCC also displayed good internal reliability
      (Cronbach'salpha =0.91) and good test-retest reliability (intraclass correlation
      coefficient = 0.77; p <.01). The CHLCC is a valid and reliable measure for
      assessing health literacy among Chinese patients with chronic illness. The scale
      could be used by practitioners before implementing health promotion and
      education.

PMID- 24093358
TI  - The association between health literacy and cancer-related attitudes, behaviors,
      and knowledge.
AB  - Using a multidimensional assessment of health literacy (the Cancer Message
      Literacy Test-Listening, the Cancer Message Literacy Test-Reading, and the Lipkus
      Numeracy Scale), the authors assessed a stratified random sample of 1013 insured
      adults (40-70 years of age). The authors explored whether low health literacy
      across all 3 domains (n =111) was associated with sets of variables likely to
      affect engagement in cancer prevention and screening activities: (a) attitudes
      and behaviors relating to health care encounters and providers, (b) attitudes
      toward cancer and health, (c) knowledge of cancer screening tests, and (d)
      attitudes toward health related media and actual media use. Adults with low
      health literacy were more likely to report avoiding doctor's visits, to have more
      fatalistic attitudes toward cancer, to be less accurate in identifying the
      purpose of cancer screening tests, and more likely to avoid information about
      diseases they did not have. Compared with other participants, those with lower
      health literacy were more likely to say that they would seek information about
      cancer prevention or screening from a health care professional and less likely to
      turn to the Internet first for such information. Those with lower health literacy
      reported reading on fewer days and using the computer on fewer days than did
      other participants. The authors assessed the association of low health literacy
      with colorectal cancer screening in an age-appropriate subgroup for which
      colorectal cancer screening is recommended. In these insured subjects receiving
      care in integrated health care delivery systems, those with low health literacy
      were less likely to be up to date on screening for colorectal cancer, but the
      difference was not statistically significant. 

PMID- 24093359
TI  - Colorectal cancer screening: low health literacy and limited English proficiency
      among Asians and Whites in California.
AB  - The authors examined the relationship between low health literacy (LHL), limited
      English proficiency (LEP), and meeting current U.S. Preventive Service Task Force
      colorectal cancer (CRC) screening guidelines for Asians and Whites in California.
      For 1,478 Asian and 14,410 White respondents 50-75 years of age in the 2007
      California Health Interview Survey, the authors examined meeting CRC screening
      guidelines using multivariable logistic models by LEP and LHL separately and in
      combination. Analyses were run with the full sample, then separately for Whites
      and Asians controlling for demographics and insurance. For those with LEP,
      patient-provider language concordance and CRC screening was examined. Overall,
      respondents with LEP and LHL were the least likely to meet CRC screening
      guidelines (36%) followed by LEP-only (45%), LHL-only (51%), and those with
      neither LHL nor LEP (59%), a hierarchy that remained significant in multivariable
      models. For Whites, LHL-only was associated with screening, whereas LEP-only and
      LEP and LHL were significant for Asians. Having a language concordant provider
      was not significantly associated with CRC screening among those with LEP. Health
      literacy is associated with CRC screening, but English proficiency is also
      critical to consider. Asians with both LEP and LHL appear particularly vulnerable
      to cancer screening disparities. 

PMID- 24093360
TI  - Health literacy associations between Hispanic elderly patients and their
      caregivers.
AB  - Knowing health literacy levels of older patients and their caregivers is
      important because caregivers assist patients in the administration of
      medications, manage daily health care tasks, and help make health services
      utilization decisions. The authors examined the association of health literacy
      levels between older Hispanic patients and their caregivers among 174 patient
      caregiver dyads enrolled from 3 community clinics and 28 senior centers in San
      Antonio, Texas. Health literacy was measured using English and Spanish versions
      of the Short-Test of Functional Health Literacy Assessment and categorized as
      "low" or "adequate." The largest dyad category (41%) consisted of a caregiver
      with adequate health literacy and patient with low health literacy. Among the
      dyads with the same health literacy levels, 28% had adequate health literacy and
      24% had low health literacy. It is notable that 7% of dyads consisted of a
      caregiver with low health literacy and a patient with adequate health literacy.
      Low health literacy is a concern not only for older Hispanic patients but also
      for their caregivers. To provide optimal care, clinicians must ensure that
      information is given to both patients and their caregivers in clear effective
      ways as it may significantly affect patient health outcomes. 

PMID- 24093361
TI  - Health literacy, numeracy, and graphical literacy among veterans in primary care
      and their effect on shared decision making and trust in physicians.
AB  - Studies reveal high levels of inadequate health literacy and numeracy in African
      Americans and older veterans. The authors aimed to investigate the distribution
      of health literacy, numeracy, and graph literacy in these populations. They
      conducted a cross-sectional survey of veterans receiving outpatient care and
      measured health literacy, numeracy, graph literacy, shared decision making, and
      trust in physicians. In addition, the authors compared subgroups of veterans
      using analyses of covariance. Participants were 502 veterans (22-82 years). Low,
      marginal, and adequate health literacy were found in, respectively, 29%, 26%, and
      45% of the veterans. The authors found a significant main effect of race
      qualified by an age and race interaction. Inadequate health literacy was more
      common in African Americans than in Whites. Younger African Americans had lower
      health literacy (p <.001), graph literacy (p <.001), and numeracy (p <.001) than
      did Whites, even after the authors adjusted for covariates. Older and younger
      participants did not differ in health literacy, objective numeracy, or graph
      literacy after adjustment. The authors found no health literacy or age-related
      differences regarding preferences for shared decision making. African Americans
      expressed dissatisfaction with their current role in decision making (p =.03).
      Older participants trusted their physicians more than younger participants (p
      =.01). In conclusion, African Americans may be at a disadvantage when reviewing
      patient education materials, potentially affecting health care outcomes. 

PMID- 24093362
TI  - Health literacy and complementary and alternative medicine use among underserved
      inpatients in a safety net hospital.
AB  - Little is known about the relationship between health literacy and complementary
      and alternative medicine (CAM) use in low-income racially diverse patients. The
      authors conducted a secondary analysis of baseline data from 581 participants
      enrolled in the Re-Engineered Discharge clinical trial. The authors assessed
      sociodemographic characteristics, CAM use, and health literacy. They used
      bivariate and multivariate logistic regression to test the association of health
      literacy with four patterns of CAM use. Of the 581 participants, 50% reported
      using any CAM, 28% used provider-delivered CAM therapies, 27% used relaxation
      techniques, and 21% used herbal medicine. Of those with higher health literacy,
      55% used CAM. Although there was no association between health literacy and CAM
      use for non-Hispanic Black participants, non-Hispanic White (OR = 3.68, 95% CI
      [1.27, 9.99]) and Hispanic/other race (OR = 3.40, 95% CI [1.46, 7.91])
      participants were significantly more likely to use CAM if they had higher health
      literacy. For each racial/ethnic group, there were higher odds of using
      relaxation techniques among those with higher health literacy. Underserved
      hospitalized patients use CAM. Regardless of race, patients with high health
      literacy make greater use of relaxation techniques.

PMID- 24093365
TI  - True parity would be a fitting tribute to Sharon.

PMID- 24093364
TI  - Using single-molecule approaches to study archaeal DNA-binding protein Alba1.
AB  - Thermophilic and hyperthermophilic archaea have one or more copies of the Alba
      gene, which encodes Alba, a dimeric, highly basic protein that binds
      cooperatively to DNA. However, the functions of Alba and how it interacts with
      DNA remain unclear. In this study, we have used single-molecule tethered particle
      motion (TPM) and optical tweezers (OT) experiments to study the interactions
      between DNA molecules and Alba1. When Alba1 binds to double-stranded DNA, the
      Brownian motion (BM) amplitude for DNA tethers increases continuously, suggesting
      that Alba1 binds cooperatively. The OT study confirmed that a 5-fold increase in
      the persistence length of the Alba1 nucleoprotein filament is the major factor
      causing the increase in the BM amplitude for DNA tethers, while the contour
      length remained mostly unchanged. Moreover, the rate of the increase in the BM
      amplitude and the BM plateau value are both DNA length-dependent, indicating that
      the number of Alba1 initiation binding sites increases as the DNA becomes longer.
      Using the incoming-strand TPM experiment to monitor the interaction between Alba1
      nucleoprotein filaments, we found that significant dimer-dimer contacts between
      two Alba1 nucleoprotein filaments are present, and the interaction is regulated
      by the concentration of Alba1.

PMID- 24093366
TI  - RCN warns of burnout as nurses feel pressure to work despite being ill.

PMID- 24093372
TI  - Unions prepare to do battle to win at least a 1 per cent rise for nurses.

PMID- 24093377
TI  - NICE highlights need to address infection risks of self-injection.

PMID- 24093381
TI  - Cash for student placements will help promote primary care jobs.

PMID- 24093383
TI  - BME nurses deliver timely advice on what matters most to them.
AB  - Nurse leaders including management consultants, university lecturers and a
      director of nursing at an independent hospital gathered to share their expertise
      at a recent meeting in Nottingham. 

PMID- 24093389
TI  - 'You have to be the best'.

PMID- 24093390
TI  - Still no room at the top.
AB  - Despite years of the initiatives designed to support a diverse workforce, few top
      level positions are filled by black and minority ethnic people. Opening top jobs
      to BME staff is still not a priority for the NHS, says the NHS Leadership
      Academy's Yvonne Coghill.

PMID- 24093391
TI  - Not black and white.
AB  - Black African nurses in the UK may experience greater job barriers than other
      overseas or BME workers. In this article, senior nurses call for action: the NHS
      must stop wasting the potential of African nurses and all BME groups should
      support one another.

PMID- 24093392
TI  - 'My appointment changed everything and the pattern had been broken'.

PMID- 24093393
TI  - History of partnership.

PMID- 24093407
TI  - Female genital mutilation and visual checks on schoolgirls.

PMID- 24093408
TI  - The differences between stress, burnout and compassion fatigue.

PMID- 24093410
TI  - Good ideas can get left behind with restructuring and change.

PMID- 24093409
TI  - Stop questioning safe staffing levels and believe the evidence presented.

PMID- 24093412
TI  - Using term 'sitters' for hospice at home staff is demeaning.

PMID- 24093413
TI  - Using blackmail tactics on flu vaccinations is unacceptable.

PMID- 24093414
TI  - Credit where it is due for photo of nurse heroism tale author.

PMID- 24093415
TI  - Role of the specialist nurse in caring for patients with myeloma.
AB  - Myeloma is a rare, heterogeneous cancer of the bone marrow. It is characterised
      by a range of comorbidities and clinical complications, including bone fractures,
      anaemia and kidney damage. Myeloma is an individual cancer both in terms of the
      symptoms and complications patients can experience and in their response to
      treatment. This means that patients require individual management and care from
      specialist nurses who provide information, education, and social and
      psychological support, as well as direct patient care. The different combinations
      of treatment include complicated chemotherapy and anti-myeloma regimens. These
      treatments result in an accumulation of toxicities in patients, which specialist
      nurses play a vital role in monitoring and managing. The support and care given
      by specialist nurses have an effect both on the patient experience and patient
      outcomes. 

PMID- 24093416
TI  - Post-operative urinary retention.
AB  - Urinary retention is a common complication of surgery and anaesthesia. The risk
      of post-operative urinary retention is increased following certain surgical
      procedures and anaesthetic modalities, and with patients' advancing age. Patients
      at increased risk of post-operative urinary retention should be identified before
      surgery or the condition should be identified and treated in a timely manner
      following surgery. If conservative measures do not help the patient to pass
      urine, the bladder will need to be drained using either an intermittent catheter
      or an indwelling urethral catheter, which can result in catheter-associated
      urinary tract infections. This article provides an overview of normal bladder
      function, risk factors for developing post-operative urinary retention, and
      treatment options. Guidance drawn from the literature aims to assist nurses in
      identifying at-risk patients and inform patient care. 

PMID- 24093417
TI  - Assessment and treatment of patients with acute tachyarrhythmia.
AB  - A tachyarrhythmia is defined as a heart rate greater than 100 beats per minute in
      conjunction with abnormal cardiac conduction. This article aims to inform nurses
      and other healthcare professionals about the predominant acute tachyarrhythmias.
      It focuses on the assessment and management of patients with this condition using
      case study examples. 

PMID- 24093418
TI  - An individual focus.

PMID- 24093419
TI  - In need of outside help.

PMID- 24093420
TI  - Follow Seacole into leadership.

PMID- 24093422
TI  - Prejudice in the workplace.

PMID- 24093423
TI  - Investing in a diverse future.

PMID- 24093424
TI  - Guide: a desktop application for analysing gene expression data.
AB  - BACKGROUND: Multiplecompeting bioinformatics tools exist for next-generation
      sequencing data analysis. Many of these tools are available as R/Bioconductor
      modules, and it can be challenging for the bench biologist without any
      programming background to quickly analyse genomics data. Here, we present an
      application that is designed to be simple to use, while leveraging the power of R
      as the analysis engine behind the scenes. RESULTS: Genome Informatics Data
      Explorer (Guide) is a desktop application designed for the bench biologist to
      analyse RNA-seq and microarray gene expression data. It requires a text file of
      summarised read counts or expression values as input data, and performs
      differential expression analyses at both the gene and pathway level. It uses well
      established R/Bioconductor packages such as limma for its analyses, without
      requiring the user to have specific knowledge of the underlying R functions.
      Results are presented in figures or interactive tables which integrate useful
      data from multiple sources such as gene annotation and orthologue data. Advanced
      options include the ability to edit R commands to customise the analysis
      pipeline. CONCLUSIONS: Guide is a desktop application designed to query gene
      expression data in a user-friendly way while automatically communicating with R.
      Its customisation options make it possible to use different bioinformatics tools
      available through R/Bioconductor for its analyses, while keeping the core usage
      simple. Guide is written in the cross-platform framework of Qt, and is freely
      available for use from http://guide.wehi.edu.au.

PMID- 24093425
TI  - The fetal head evaluation during labor in the occiput posterior position: the ESA
      (evaluation by simulation algorithm) approach.
AB  - The determination of fetal head position can be useful in labor to predict the
      success of labor management, especially in case of malpositions. Malpositions are
      abnormal positions of the vertex of the fetal head and account for the large part
      of indication for cesarean sections for dystocic labor. The occiput posterior
      position occurs in 15-25% of patients before labor at term and, however, most
      occiput posterior presentations rotate during labor, so that the incidence of
      occiput posterior at vaginal birth is approximately 5-7%. Persistence of the
      occiput posterior position is associated with higher rate of interventions and
      with maternal and neonatal complications and the knowledge of the exact position
      of the fetal head is of paramount importance prior to any operative vaginal
      delivery, for both the safe positioning of the instrument that may be used (i.e.
      forceps versus vacuum) and for its successful outcome. Ultrasound (US) diagnosed
      occiput posterior position during labor can predict occiput posterior position at
      birth. By these evidences, the time requested for fetal head descent and the
      position in the birth canal, had an impact on the diagnosis of labor progression
      or arrested labor. To try to reduce this pitfalls, authors developed a new
      algorithm, applied to intrapartum US and based on suitable US pictures, that sets
      out, in detail, the quantitative evaluation, in degrees, of the occiput posterior
      position of the fetal head in the pelvis and the birth canal, respectively, in
      the first and second stage of labor. Authors tested this computer system in a
      settle of patients in labor.

PMID- 24093427
TI  - Childhood stressors in the development of fatigue syndromes: a review of the past
      20 years of research.
AB  - BACKGROUND: Chronic fatigue syndrome (CFS) and fibromyalgia (FM) are both highly
      prevalent conditions associated with extreme disability and with the development
      of co-morbid psychiatric disorders, such as depression and anxiety. Childhood
      stressors have been shown to induce persistent changes in the function of
      biological systems potentially relevant to the pathogenesis of both CFS and FM,
      such as the inflammatory system and the hypothalamic-pituitary-adrenal (HPA)
      axis. In this review, we examined whether multiple forms of childhood stressors
      are contributing factors to the development of these disorders, and of the
      associated psychiatric symptoms. METHOD: Using PubMed, we identified 31 papers
      relevant to this narrative review. We included cohort studies and case-control
      studies, without any exclusion in terms of age and gender. No study
      characteristics or publication date restrictions were imposed. RESULTS: Most
      studies across the literature consistently show that there is a strong
      association between experiences of childhood stressors and the presence of CFS
      and FM, with rates of CFS/FM being two- to three-fold higher in exposed than in
      unexposed subjects. We also found evidence for an increased risk for the
      development of additional symptoms, such as depression, anxiety and pain, in
      individuals with CFS and FM with a previous history of childhood stressors,
      compared with individuals with CFS/FM and no such history. CONCLUSIONS: Our
      review confirms that exposure to childhood stressors is associated with the
      subsequent development of fatigue syndromes such as CFS and FM, and related
      symptoms. Further studies are needed to identify the mechanisms underlying these
      associations.

PMID- 24093426
TI  - Dose-dependent effects of NY-ESO-1 protein vaccine complexed with cholesteryl
      pullulan (CHP-NY-ESO-1) on immune responses and survival benefits of esophageal
      cancer patients.
AB  - BACKGROUND: Cholesteryl pullulan (CHP) is a novel antigen delivery system for
      cancer vaccines. This study evaluated the safety, immune responses and clinical
      outcomes of patients who received the CHP-NY-ESO-1 complex vaccine, Drug code:
      IMF-001. METHODS: Patients with advanced/metastatic esophageal cancer were
      enrolled and subcutaneously vaccinated with either 100 MUg or 200 MUg of NY-ESO-1
      protein complexed with CHP. The primary endpoints were safety and humoral immune
      responses, and the secondary endpoint was clinical efficacy. RESULTS: A total of
      25 patients were enrolled. Thirteen and twelve patients were repeatedly
      vaccinated with 100 MUg or 200 MUg of CHP-NY-ESO-1 with a median of 8 or 9.5
      doses, respectively. No serious adverse events related to the vaccine were
      observed. Three out of 13 patients in the 100-MUg cohort and 7 out of 12 patients
      in the 200-MUg cohort were positive for anti-NY-ESO-1 antibodies at baseline. In
      the 100-MUg cohort, an antibody response was observed in 5 out of 10 pre-antibody
      negatives patients, and the antibody levels were augmented in 2 pre-antibody
      positive patients after vaccination. In the 200-MUg cohort, all 5 pre-antibody
      negative patients became seropositive, and the antibody level was amplified in
      all 7 pre-antibody-positive patients. No tumor shrinkage was observed. The
      patients who received 200 MUg of CHP-NY-ESO-1 survived longer than patients
      receiving 100 MUg of CHP-NY-ESO-1, even those who exhibited unresponsiveness to
      previous therapies or had higher tumor burdens. CONCLUSIONS: The safety and
      immunogenicity of CHP-NY-ESO-1 vaccine were confirmed. The 200 MUg dose more
      efficiently induced immune responses and suggested better survival benefits.
      (Clinical trial registration number NCT01003808).

PMID- 24093428
TI  - A comparison of US and Australian men's values and preferences for PSA screening.
AB  - BACKGROUND: Patient preferences derived from an assessment of values can help
      inform the design of screening programs, but how best to do so, and whether such
      preferences differ cross-nationally, has not been well-examined. The objective of
      this study was to compare the values and preferences of Australian and US men for
      PSA (prostate specific antigen) screening. METHODS: We used an internet based
      survey of men aged 50-75 with no personal or family history of prostate cancer
      recruited from on-line panels of a survey research organization in the US and
      Australia. Participants viewed information on prostate cancer and prostate cancer
      screening with PSA testing then completed a values clarification task that
      included information on 4 key attributes: chance of 1) being diagnosed with
      prostate cancer, 2) dying from prostate cancer, 3) requiring a biopsy as a result
      of screening, and 4) developing impotence or incontinence as a result of
      screening. The outcome measures were self reported most important attribute,
      unlabelled screening test choice, and labelled screening intent, assessed on post
      task questionnaires. RESULTS: We enrolled 911 participants (US:456; AU:455), mean
      age was 59.7; 88.0% were white; 36.4% had completed at least a Bachelors' degree;
      42.0% reported a PSA test in the past 12 months. Australian men were more likely
      to be white and to have had recent screening. For both US and Australian men, the
      most important attribute was the chance of dying from prostate cancer. Unlabelled
      post-task preference for the PSA screening-like option was greater for Australian
      (39.1%) compared to US (26.3%) participants (adjusted OR 1.68 (1.28-2.22)).
      Labelled intent for screening was high for both countries: US:73.7%, AUS:78.0% (p
      = 0.308). CONCLUSIONS: There was high intent for PSA screening in both US and
      Australian men; fewer men in each country chose the PSA-like option on the
      unlabelled question. Australian men were somewhat more likely to prefer PSA
      screening. Men in both countries did not view the increased risk of diagnosis as
      a negative aspect, suggesting more work needs to be done on communicating the
      concept of overdiagnosis to men facing a PSA screening decision. TRIAL
      REGISTRATION: This trial was registered at ClinicalTrials.gov (NCT01558583).

PMID- 24093429
TI  - Microemulsion for simultaneous transdermal delivery of benzocaine and
      indomethacin: in vitro and in vivo evaluation.
AB  - This study investigated simultaneous transdermal delivery of indomethacin and
      benzocaine from microemulsion. Eucalyptus oil based microemulsion was used with
      Tween 80 and ethanol being employed as surfactant and cosurfactant, respectively.
      A microemulsion formulation comprising eucalyptus oil, polyoxyethylene sorbitan
      momooleate (Tween 80), ethanol and water (20:30:30:20) was selected. Indomethacin
      (1% w/w) and benzocaine (20% w/w) were incorporated separately or combined into
      this formulation before in vitro and in vivo evaluation. Application of
      indomethacin microemulsion enhanced the transdermal flux and reduced the lag time
      compared to saturated aqueous control. The same trend was evident for benzocaine
      microemulsion. Simultaneous application of the two drugs in microemulsion
      provided similar enhancement pattern. The in vivo evaluation employed the
      pinprick method and revealed rapid anesthesia after application of benzocaine
      microemulsion with the onset being 10 min and the action lasting for 50 min. For
      indomethacin microemulsion, the analgesic effect was recorded after 34.5 min and
      lasted for 70.5 min. Simultaneous application of benzocaine and indomethacin
      provided synergistic effect. The onset of action was achieved after 10 min and
      lasted for 95 min. The study highlighted the potential of microemulsion
      formulation in simultaneous transdermal delivery of two drugs.

PMID- 24093430
TI  - Advances in dissolution instrumentation and their practical applications.
AB  - The rising demands on discriminatory and prediction abilities of dissolution
      methods and the increasing complexity of new drug products are the main driving
      forces of the progress in this field. The research moves forward as imperfections
      and shortcomings of classical methods are being described, and where the
      capabilities of the contemporary methods are insufficient, new methods are being
      developed. The review discusses these advances with respect to the issues that
      currently draw the most attention, i.e. correct simulation of hydrodynamics and
      stress forces, maintenance of sink conditions, study of precipitation, use of
      biorelevant media and the employment of more physiologically relevant methods in
      general.

PMID- 24093431
TI  - Lyophilized insulin nanoparticles prepared from quaternized N-aryl derivatives of
      chitosan as a new strategy for oral delivery of insulin: in vitro, ex vivo and in
      vivo characterizations.
AB  - OBJECTIVE: The purpose of this research was the development, in vitro, ex vivo
      and in vivo characterization of lyophilized insulin nanoparticles prepared from
      quaternized N-aryl derivatives of chitosan. METHODS: Insulin nanoparticles were
      prepared from methylated N-(4-N,N-dimethylaminobenzyl), methylated N-(4
      pyridinyl) and methylated N-(benzyl). Insulin nanoparticles containing non
      modified chitosan and also trimethyl chiotsan (TMC) were also prepared as
      control. The effects of the freeze-drying process on physico-chemical properties
      of nanoparticles were investigated. The release of insulin from the nanoparticles
      was studied in vitro. The mechanism of the release of insulin from different
      types of nanoparticles was determined using curve fitting. The secondary
      structure of the insulin released from the nanoparticles was analyzed using
      circular dichroism and the cell cytotoxicity of nanoparticles on a Caco-2 cell
      line was determined. Ex vivo studies were performed on excised rat jejunum using
      Frantz diffusion cells. In vivo studies were performed on diabetic male Wistar
      rats and blood glucose level and insulin serum concentration were determined.
      RESULTS: Optimized nanoparticles with proper physico-chemical properties were
      obtained. The lyophilization process was found to cause a decrease in zeta
      potential and an increase in PdI as well as and a decrease in entrapment
      efficiency (EE%) and loading efficiency (LE%) but conservation in size of
      nanoparticles. Atomic force microscopy (AFM) images showed non-aggregated, stable
      and spherical to sub-spherical nanoparticles. The in vitro release study revealed
      higher release rates for lyophilized compared to non-lyophilized nanoparticles.
      Cytotoxicity studies on Caco-2 cells revealed no significant cytotoxicity for
      prepared nanoparticles after 3-h post-incubation but did show the concentration
      dependent cytotoxicity after 24 h. The percentage of cumulative insulin
      determined from ex vivo studies was significantly higher in nanoparticles
      prepared from quaternized aromatic derivatives of chitosan. In vivo data showed
      significantly higher insulin intestinal absorption in nanoparticles prepared from
      methylated N-(4-N, N-dimethylaminobenzyl) chitosan nanoparticles compared to
      trimethyl chitosan. CONCLUSION: These data obtained demonstrated that as the
      result of optimized physico-chemical properties, drug release rate, cytotoxicity
      profile, ex vivo permeation enhancement and increased in vivo absorption,
      nanoparticles prepared from N-aryl derivatives of chitosan can be considered as
      valuable method for the oral delivery of insulin.

PMID- 24093433
TI  - Clinical review: tuberculosis on the intensive care unit.
AB  - Rates of tuberculosis (TB) are increasing in most west European nations. Patients
      with TB can be admitted to an ICU for a variety of reasons, including respiratory
      failure, multiorgan failure and decreased consciousness associated with central
      nervous system disease. TB is a treatable disease but the mortality for patients
      admitted with TB to an ICU remains high. Management challenges exist in
      establishing a prompt diagnosis and administering effective treatment on the ICU
      with potentially poor gastric absorption and high rates of organ dysfunction and
      drug toxicity. In this review reasons for ICU admission, methods of achieving a
      confident diagnosis through direct and inferred methods, anti-tuberculosis
      treatment (including steroid and other adjuvant therapies) and specific
      management problems with particular relevance to the intensivist are discussed.
      The role of therapeutic drug monitoring, judicious use of alternative regimes in
      the context of toxicity or organ dysfunction and when to suspect paradoxical
      tuberculosis reactions are also covered. Diagnostic and therapeutic algorithms
      are proposed to guide ICU doctors in the management of this sometimes complicated
      disease. 

PMID- 24093434
TI  - HSV-1 cutaneous infection in a patient with Hodgkin's lymphoma treated with
      brentuximab vedotin.

PMID- 24093432
TI  - Redox-mediated and ionizing-radiation-induced inflammatory mediators in prostate
      cancer development and treatment.
AB  - SIGNIFICANCE: Radiation therapy is widely used for treatment of prostate cancer.
      Radiation can directly damage biologically important molecules; however, most
      effects of radiation-mediated cell killing are derived from the generated free
      radicals that alter cellular redox status. Multiple proinflammatory mediators can
      also influence redox status in irradiated cells and the surrounding
      microenvironment, thereby affecting prostate cancer progression and radiotherapy
      efficiency. RECENT ADVANCES: Ionizing radiation (IR)-generated oxidative stress
      can regulate and be regulated by the production of proinflammatory mediators.
      Depending on the type and stage of the prostate cancer cells, these
      proinflammatory mediators may lead to different biological consequences ranging
      from cell death to development of radioresistance. CRITICAL ISSUES: Tumors are
      heterogeneous and dynamic communication occurs between stromal and prostate
      cancer cells, and complicated redox-regulated mechanisms exist in the tumor
      microenvironment. Thus, antioxidant and anti-inflammatory strategies should be
      carefully evaluated for each patient at different stages of the disease to
      maximize therapeutic benefits while minimizing unintended side effects. FUTURE
      DIRECTIONS: Compared with normal cells, tumor cells are usually under higher
      oxidative stress and secrete more proinflammatory mediators. Thus, redox status
      is often less adaptive in tumor cells than in their normal counterparts. This
      difference can be exploited in a search for new cancer therapeutics and treatment
      regimes that selectively activate cell death pathways in tumor cells with minimal
      unintended consequences in terms of chemo- and radio-resistance in tumor cells
      and toxicity in normal tissues.

PMID- 24093436
TI  - Current treatment for nocardia infections.
AB  - INTRODUCTION: Nocardiosis is an infectious actinomycetic disease with a variable
      clinical spectrum that makes it difficult to diagnose. It mainly affects
      immunosuppressed individuals. Advances in molecular genomic technology have
      helped in identifying new pathogenic Nocardia species. This has made
      identification of their specific antimicrobial sensitivity possible. AREAS
      COVERED: It is important to know the taxonomy, clinical features, diagnosis and
      precise species identification because of the multitude of pathogenic species
      involved and the different antibiotic susceptibility patterns. The authors review
      sulfonamides, aminoglycosides, penicillin derivatives, tetracyclines,
      glycylcyclines, oxazolidinones, carbapenems and the association of other
      potential drugs, the therapeutic effectiveness of traditional antimicrobials and
      new monotherapy and combined treatment alternatives. New oxazolidinones and the
      benzothiazinones are compounds that have been found effective in vitro and in
      experimental models. EXPERT OPINION: Clinicians should be aware of nocardiosis in
      patients with different forms of immunosuppression. The identification of
      organisms, their patterns of antibiotic susceptibility and the adverse effects
      related to these drugs must be considered. Treatments can vary from traditional
      schemes with trimethoprim-sulfamethoxazole to other combination therapies and new
      antibiotics and treatment modalities depending on the organ or site involved, the
      severity of infection and the presence of comorbidities.

PMID- 24093437
TI  - Injury pattern, hospital triage, and mortality of 1250 patients with severe
      traumatic brain injury caused by road traffic accidents.
AB  - This epidemiological study analyzed the incidence, risk factors, hospital triage,
      and outcome of patients with severe traumatic brain injuries (sTBIs) caused by
      road traffic accidents (RTAs) admitted to hospitals in the Trauma Center West
      Netherlands (TCWN) region. Trauma registry data were used to identify TBI in all
      RTA victims admitted to hospitals in the mid-West region of the Netherlands from
      2003 to 2011. Type of head injury and severity were classified using the
      Abbreviated Injury Scale (AIS). Head injuries with AIS severity scores >= 3 were
      considered sTBI. Ten percent of all 12,503 hospital-admitted RTA victims
      sustained sTBI, ranging from 5.4% in motorcyclists, 7.4% in motorists, 9.6% in
      cyclists, and 12.7% in moped riders to 15.1% in pedestrians (p<0.0001). Among RTA
      victims admitted to hospital, sTBI was most prevalent in pedestrians (odds ratio
      [OR], 2.25; 95% confidence interval [CI], 1.78-2.86) and moped riders (OR, 1.86;
      95% CI, 1.51-2.30). Injury patterns differed between road user groups. Incidence
      of contusion ranged from 46.6% in cyclists to 74.2% in motorcyclists, whereas
      basilar and open-skull fractures were least common in motorcyclists (22.6%) and
      most common in moped riders (51.5%). Hemorrhage incidence ranged from 44.9%
      (motorists) to 63.6% (pedestrians). Subdural and -arachnoid bleedings were most
      frequent. Age, Glasgow Coma Scale, and type of hemorrhage were independent
      prognostic factors for in-hospital mortality after sTBI. In-hospital mortality
      ranged from 4.2% in moped riders to 14.1% in motorists. Pedestrians have the
      highest risk to sustain sTBI and, more specifically, intracranial hemorrhage.
      Hemorrhage and contusion both occur in over 50% of patients with sTBI. Specific
      brain injury patterns can be distinguished for specific road user groups, and
      independent prognostic risk factors for sTBI were identified. This knowledge may
      be used to improve vigilance for particular injuries in specific patient groups
      and stimulate development of focused diagnostic strategies.

PMID- 24093435
TI  - Integral role of platelet-derived growth factor in mediating transforming growth
      factor-beta1-dependent mesenchymal stem cell stiffening.
AB  - Mesenchymal stem cells (MSCs) play an important role in matrix remodeling,
      fibroblast activation, angiogenesis, and immunomodulation and are an integral
      part of fibrovascular networks that form in developing tissues and tumors. The
      engraftment and function of MSCs in tissue niches is regulated by a multitude of
      soluble proteins. Transforming growth factor-beta1 (TGF-beta1) and platelet
      derived growth factor-BB (PDGF) have previously been recognized for their role in
      MSC biology; thus, we sought to investigate their function in mediating MSC
      mechanics and matrix interactions. Cytoskeletal organization, characterized by
      cell elongation, stress fiber formation, and condensation of actin and
      microtubules, was dramatically affected by TGF-beta1, individually and in
      combination with PDGF. The intracellular mechanical response to these stimuli was
      measured with particle tracking microrheology. MSCs stiffened in response to TGF
      beta1 (their elastic moduli was ninefold higher than control cells), a result
      that was enhanced by the addition of PDGF (100-fold change). Blocking TGF-beta1
      or PDGF signaling with inhibitors SB-505124 or JNJ-10198409, respectively,
      reversed soluble-factor-induced stiffening, indicating that crosstalk between
      these two pathways is essential for stiffening response. A genome-wide microarray
      analysis revealed TGF-beta1-dependent regulation of cytoskeletal actin-binding
      protein genes. Actin crosslinking and bundling protein genes, which regulate
      cytosolic rheology through changes in semiflexible actin polymer meshwork, were
      upregulated with TGF-beta1 treatment. TGF-beta1 alone and in combination with
      PDGF also amplified surface integrin expression and adhesivity of MSCs with
      extracellular matrix proteins. These findings will provide a more mechanistic
      insight for modeling tissue-level rigidity in fibrotic tissues and tumors. 

PMID- 24093438
TI  - Prevalence of eye diseases among school children in a rural south-eastern
      Nigerian community.
AB  - INTRODUCTION: Vision has an essential role in a child's development, and visual
      deficit is a risk factor not only for altered visio-sensory development, but also
      for overall socioeconomic status throughout life. Early detection provides the
      best opportunity for effective treatment of eye and vision problems in children.
      Therefore, timely screening is vital to avoid lifelong visual impairment. There
      is a paucity of data regarding the causes of eye disease among rural children in
      Nigeria. The aim of this study was to determine the prevalence and causes of eye
      disease among children residing in rural communities in Nigeria. METHODS: A cross
      sectional survey was conducted to determine the prevalence and common causes of
      ocular morbidities in primary school children in Abagana, a rural community in
      Njikoka Local Government Area of Anambra State, South-East Nigeria. Children aged
      6-16 years in all 8 primary schools were registered, interviewed and their eyes
      examined. Data were analyzed according to age, sex, type of ocular disorder and
      causes of visual impairment. Frequency and percentages were calculated with
      univariate analysis and parametric method. RESULTS: The census population
      consisted of 2092 children, 1081 (51.7%) males, with a male to female ratio of
      1.07:1. Ocular disorders were found in 127 (6.1%) of the population. The most
      common ocular disorders in this community were vernal conjunctivitis 61 (2.9%)
      followed by refractive error 14 (0.7%). Amblyiopia, which is avoidable, was the
      most common cause of visual impairment. CONCLUSION: Study findings indicated that
      early detection through early eye screening; health education and access to a
      quality eye care facility will reduce the burden of eye disease and blindness
      among rural Nigerian children.

PMID- 24093439
TI  - 3D super-resolution imaging with blinking quantum dots.
AB  - Quantum dots are promising candidates for single molecule imaging due to their
      exceptional photophysical properties, including their intense brightness and
      resistance to photobleaching. They are also notorious for their blinking. Here we
      report a novel way to take advantage of quantum dot blinking to develop an
      imaging technique in three-dimensions with nanometric resolution. We first
      applied this method to simulated images of quantum dots and then to quantum dots
      immobilized on microspheres. We achieved imaging resolutions (fwhm) of 8-17 nm in
      the x-y plane and 58 nm (on coverslip) or 81 nm (deep in solution) in the z
      direction, approximately 3-7 times better than what has been achieved previously
      with quantum dots. This approach was applied to resolve the 3D distribution of
      epidermal growth factor receptor (EGFR) molecules at, and inside of, the plasma
      membrane of resting basal breast cancer cells. 

PMID- 24093440
TI  - Comparison of the membrane proteome of virulent Mycobacterium tuberculosis and
      the attenuated Mycobacterium bovis BCG vaccine strain by label-free quantitative
      proteomics.
AB  - The Mycobacterium tuberculosis membrane is rich in antigens that are potential
      targets for diagnostics and the development of new vaccines. To better understand
      the mechanisms underlying MTB virulence and identify new targets for therapeutic
      intervention, we investigated the differential composition of membrane proteomes
      between virulent M. tuberculosis H37Rv (MTB) and the Mycobacterium bovis BCG
      vaccine strain. To compare the membrane proteomes, we used LC-MS/MS analysis in
      combination with label-free quantitative proteomics, utilizing the area under the
      curve of the extracted ion chromatograms of peptides obtained from m/z and
      retention time alignment of MS1 features. With this approach, we obtained
      relative abundance ratios for 2203 identified membrane-associated proteins in
      high confidence. Of these proteins, 294 showed statistically significant
      differences of at least two fold in relative abundance between MTB and BCG
      membrane fractions. Our comparative analysis detected several proteins associated
      with known genomic regions of difference between MTB and BCG as being absent,
      which validated the accuracy of our approach. In further support of our label
      free quantitative data, we verified select protein differences by immunoblotting.
      To our knowledge, we have generated the first comprehensive and high-coverage
      profile of comparative membrane proteome changes between virulent MTB and its
      attenuated relative BCG, which helps elucidate the proteomic basis of the
      intrinsic virulence of the MTB pathogen. 

PMID- 24093442
TI  - Amine superbases stabilized by extended hydrogen bond networks.
AB  - Extended hydrogen-bonding networks as a mechanism for creating superbases is
      explored through six different amine scaffolds: linear acenes, cyclohexane,
      decalin, triptycene, adamantane, and [2.2]paracyclophane. The gas-phase proton
      affinities of 21 different potential superbases were computed at the omegaB97X
      D/6-311+G(2d,p) level. This method was benchmarked against the experimental
      proton affinities of 44 nitrogen bases. Extended hydrogen-bonding networks,
      including second- and third-layer hydrogen bonding, led to bases with proton
      affinities 20 kcal mol(-1) greater than that of bis(dimethylamino)naphthalene.
      The strongest bases are the decalin base 25 and the adamantane base 31. 

PMID- 24093441
TI  - A novel use of gentamicin in the ROS-mediated sensitization of NCI-H460 lung
      cancer cells to various anticancer agents.
AB  - Aminoglycosides are broad-spectrum antibiotics that are used for the treatment of
      severe Gram-negative and Gram-positive bacterial infections. While bactericidal
      effects of aminoglycosides are due to binding to the 30S subunit of the bacterial
      ribosome, aminoglycosides can affect protein synthesis, intracellular calcium
      levels, and levels of reactive oxygen species (ROS) in eukaryotic cells. While
      aminoglycosides can be cytotoxic at high concentrations, our results show that at
      much lower doses, gentamicin can be implemented as a sensitizing agent for the
      NSCLC cell line NCI-H460, increasing the efficacy of camptothecin, digitoxin, and
      vinblastine in vitro. We have also established that this sensitization is reliant
      on the ROS response generated by gentamicin. 

PMID- 24093443
TI  - Assessing positive mental health in people with chronic physical health problems:
      correlations with socio-demographic variables and physical health status.
AB  - BACKGROUND: A holistic perspective on health implies giving careful consideration
      to the relationship between physical and mental health. In this regard the
      present study sought to determine the level of Positive Mental Health (PMH) among
      people with chronic physical health problems, and to examine the relationship
      between the observed levels of PMH and both physical health status and socio
      demographic variables. METHODS: The study was based on the Multifactor Model of
      Positive Mental Health (Lluch, 1999), which comprises six factors: Personal
      Satisfaction (F1), Prosocial Attitude (F2), Self-control (F3), Autonomy (F4),
      Problem-solving and Self-actualization (F5), and Interpersonal Relationship
      Skills (F6). The sample comprised 259 adults with chronic physical health
      problems who were recruited through a primary care center in the province of
      Barcelona (Spain). Positive mental health was assessed by means of the Positive
      Mental Health Questionnaire (Lluch, 1999). RESULTS: Levels of PMH differed,
      either on the global scale or on specific factors, in relation to the following
      variables: age: global PMH scores decreased with age (r=-0.129; p=0.038); b)
      gender: men scored higher on F1 (t=2.203; p=0.028) and F4 (t=3.182; p=0.002),
      while women scored higher on F2 (t -3.086; p=0.002) and F6 (t=-2.744; p=0.007);
      c) number of health conditions: the fewer the number of health problems the
      higher the PMH score on F5 (r=-0.146; p=0.019); d) daily medication:
      polymedication patients had lower PMH scores, both globally and on various
      factors; e) use of analgesics: occasional use of painkillers was associated with
      higher PMH scores on F1 (t=-2.811; p=0.006). There were no significant
      differences in global PMH scores according to the type of chronic health
      condition. The only significant difference in the analysis by factors was that
      patients with hypertension obtained lower PMH scores on the factor Autonomy
      (t=2.165; p=0.032). CONCLUSIONS: Most people with chronic physical health
      problems have medium or high levels of PMH. The variables that adversely affect
      PMH are old age, polypharmacy and frequent consumption of analgesics. The type of
      health problem does not influence the levels of PMH. Much more extensive studies
      with samples without chronic pathology are now required in order to be able to
      draw more robust conclusions.

PMID- 24093445
TI  - I copy, therefore I publish.

PMID- 24093444
TI  - Circulating microRNAs have a sex-specific association with metabolic syndrome.
AB  - BACKGROUND: The microRNAs let-7 g and miR-221 have been demonstrated to be
      related to the glucose metabolism. This study assessed the serum levels of these
      two microRNAs in subjects with and without metabolic syndrome (MetS). RESULTS:
      The serum microRNA levels were detected in 102 subjects aged 40 to 80 years who
      were recruited from the general population. The status of MetS was defined by the
      Adult Treatment Panel III (ATP III) criteria modified for Asians. Subjects with
      histories of cardiovascular diseases or who were receiving treatment with
      hypoglycemic or lipid-lowering agents were excluded. The levels of both
      circulating microRNAs (let-7 g and miR-221) were higher in subjects with MetS (p
      = 0.004 and p = 0.01, respectively). The sex-specific analysis showed that the
      difference was more prominent in women (for both miRNAs, p < 0.05 in women and p
      > 0.1 in men). In the female subjects, increased expression of both microRNAs was
      associated with an increased number of MetS risk components (p = 0.002 for let-7
      g and p = 0.022 for miR-221). Moreover, the elevation of serum let-7 g was
      significantly associated with a low level of high-density lipoprotein cholesterol
      (p = 0.022) and high blood pressure (p = 0.023). In contrast, the miR-221 level
      was not associated with any individual MetS risk component. CONCLUSIONS: The
      circulating levels of let-7 g and miR-221 displayed a female-specific elevation
      in individuals with metabolic syndrome.

PMID- 24093446
TI  - Luminescent tris(8-hydroxyquinolates) of bismuth(III).
AB  - Luminescent homoleptic bismuth(III) complexes have been synthesized by adding
      several functionalized 8-hydroxyquinolate ligands to bismuth(III) chloride in a
      3:1 mole ratio in either ethanol or tetrahydrofuran (THF) solvent. These
      complexes have been characterized by single-crystal X-ray diffraction (XRD)
      analysis, UV-vis spectroscopy, fluorescence spectroscopy, and density functional
      theory (DFT) calculations to determine their structures and photophysical
      properties. Reversible dimerization of the mononuclear tris(hydroxyquinolate)
      complexes was observed in solution and quantified using UV-vis spectroscopy. The
      fluorescence spectra show a blue shift for the monomer compared with homoleptic
      aluminum(III) hydroxyquinolate compounds. Four dimeric compounds and one
      monomeric isomer were characterized structurally. The bismuth(III) centers in the
      dimers are bridged by two oxygen atoms from the substituted hydroxyquinolate
      ligands. The more sterically hindered quinolate complex, tris(2-(diethoxymethyl)
      8-quinolinato)bismuth, crystallizes as a monomer. The complexes all exhibit low
      lying absorption and emission spectral features attributable to transitions
      between the HOMO (pi orbital localized on the quinolate phenoxide ring) and LUMO
      (pi* orbital localized on the quinolate pyridyl ring). Excitation and emission
      spectra show a concentration dependence in solution that suggests that a monomer
      dimer equilibrium occurs. Electronic structure DFT calculations support trends
      seen in the experimental results with a HOMO-LUMO gap of 2.156 eV calculated for
      the monomer that is significantly larger than those for the dimers (1.772 and
      1.915 eV). The close face to face approach of two quinolate rings in the dimer
      destabilizes the uppermost occupied quinolate pi orbitals, which reduces the HOMO
      LUMO gap and results in longer wavelength absorption and emission spectral
      features than in the monomer form. 

PMID- 24093447
TI  - Severe thrombocytopenia after trastuzumab retreatment: a case report.
AB  - BACKGROUND: Trastuzumab prolongs survival of human epidermal growth factor
      receptor 2-positive breast cancer patients in both the adjuvant and metastatic
      settings. Currently toxicity data are not available on retreatment of metastatic
      breast cancer patients who relapse after adjuvant trastuzumab. We report one
      patient with metastatic breast cancer who developed acute thrombocytopenia after
      trastuzumab infusion. This patient had trastuzumab treatment in the adjuvant
      setting. CASE PRESENTATION: A 70-year-old Caucasian woman received a diagnosis of
      metastatic breast cancer four years after her initial diagnosis of locally
      advanced, hormone receptors-positive, human epidermal growth factor receptor 2
      positive breast cancer. Trastuzumab retreatment was planned. Less than 24 hours
      after trastuzumab infusion, the patient was admitted to the hospital for the
      appearance of diffuse petechial hemorrhages and ecchymosis. The patient was
      confirmed to have a severe trastuzumab-induced thrombocytopenia. A rapid and
      complete recovery was observed after high-dose intravenous corticosteroids and
      immunoglobulin. No trastuzumab retreatment was attempted. CONCLUSION: Among the
      reported cases of trastuzumab-induced thrombocytopenia, this is the first report
      in the literature occurring in a patient retreated with trastuzumab after
      adjuvant therapy.

PMID- 24093448
TI  - Contextual determinants of maternal health care service utilization in Nigeria.
AB  - Despite the high maternal mortality ratio in Nigeria, the use of maternal health
      care services is very poor. Attempts to explain this situation has focused on
      individual level factors and the influence of community contextual factors have
      not received much attention. This study examined the relation of community
      factors to the use of antenatal care in Nigeria, and explored whether community
      factors moderated the association between individual characteristics and
      antenatal care visits. Data were drawn from the 2008 Nigeria Demographic and
      Health Survey among 16,005 women aged 15-49 years who had had their last delivery
      in the five years preceding the survey. Results from multi-level models indicated
      that living in communities with a high proportion of women who delivered in a
      health facility was associated with four or more antenatal care visits. Residence
      in high-poverty communities decreased the likelihood of antenatal care
      attendance. Living in communities with a high proportion of educated women was
      not significantly related to antenatal care visits. Community factors acted as
      moderators of the association between educational attainment and antenatal care
      attendance. Improvement in antenatal care utilization may therefore be enhanced
      by targeting poverty reduction programs and increasing health facility delivery
      in disadvantaged communities. 

PMID- 24093449
TI  - Why do some women know more? An exploration of the association of community
      socioeconomic characteristics, social capital, and HIV/AIDS knowledge.
AB  - The objective of this study was to investigate the associations of community
      level socio-economic status (SES) characteristics and social capital with women's
      knowledge of HIV/AIDS. We used a representative national sample of 6,771 women
      ages 15-49 years from the Bangladesh Demographic Health Survey of 2007. We
      extended the findings of prior studies by providing new evidence that both
      community and social capital were related to having knowledge of AIDS. The
      significant community characteristics associated with women's greater knowledge
      of AIDS were: women's higher mean age at first marriage, higher mean years of
      education, the higher percentage of women in the community who work, and higher
      mean household living standard in the community. Regardless of individual-level
      SES, living in a community with higher community-level SES and having greater
      social capital were associated with having a greater likelihood of hearing about
      AIDS. However, we found that once women knew about AIDS, not all of the community
      SES and social capital indicators explained their advanced knowledge of AIDS
      prevention and transmission. Our findings underscore the importance of HIV/AIDS
      education campaigns in the disadvantaged communities, specifically targeting
      women who are not members in any non-governmental organizations, as well as
      greater use of media in educating women about AIDS. 

PMID- 24093450
TI  - Relationship between perceived body image and recorded body mass index among
      Kuwaiti female university students.
AB  - The associations between body image and attitudes toward obesity and thinness and
      their associations with measured body mass index (BMI) among female students of
      Kuwait University (n = 137) was examined in 2008. The body image perceptions were
      assessed using nine female silhouettes figures. The difference between current
      perceived body image (PBI) and ideal body image (IBI) was used as a measure of
      body image dissatisfaction (BID). Students tended to have a bigger PBI and
      smaller IBI than would be expected from their BMI category, leading to high
      levels of BID in each BMI category. PBI, IBI, BID, RBI were highly correlated
      with each other, and BMI was significantly correlated with each of them. The
      coefficients of these associations were not significantly altered in multiple
      regression analysis by the addition of potential confounding variables, such as
      age, marital status, physical activity, dieting behavior, parental education, and
      family size. These results suggest that PBI and a desire to be thinner were
      strongly related to BID and that thinness is becoming more desired in Kuwaiti
      society than the plump body image of the past. 

PMID- 24093452
TI  - A qualitative exploration of influences on the process of recovery from personal
      written accounts of people with anorexia nervosa.
AB  - Less than half of people with anorexia nervosa achieve full recovery. Previous
      qualitative research has identified a "tipping point" for change in people who
      have experienced recovery. The present study's goal was to explore factors that
      might contribute to this time in personal published accounts, an alternate source
      for understanding lived experience. Using the 5-stage framework approach for
      thematic analysis, 31 individual (29 female) accounts were explored. These were
      purposively sampled from autobiographical accounts (during 1999-2011). In all the
      accounts a "tipping point" or change in the person's attitude toward treatment
      and recovery did appear. We identified four main themes: desire for recovery,
      positive experiences in treatment, an aspect of life outside work or study, and
      positive and helpful experiences with new or renewed relationships. The themes
      were a mix of internal and external themes, as well as themes independent of a
      treatment experience. The findings support other research that indicates
      experiences, such as personal and spiritual relationships, in addition to
      specific psychotherapies or treatments, are important in recovery. Further
      research into how to facilitate and integrate these external factors with formal
      treatment is indicated in order to improve understanding of outcomes in anorexia
      nervosa. 

PMID- 24093451
TI  - Professional women's well-being: the role of discrimination and occupational
      characteristics.
AB  - This study examined the association between perceived discrimination, workplace
      racial composition, and three outcomes-psychological distress, life
      dissatisfaction, and job dissatisfaction-among a sample of Black (n = 72) and
      White (n = 74) professional women. As a comparison, these relationships were
      analyzed to determine if they varied from those observed in more traditionally
      studied populations: Whites and non-professional Blacks, using data from a
      population of working women in the 1995 Detroit Area Study (N = 533). Perceived
      discrimination was associated with differences in psychological distress and job
      dissatisfaction but not with life dissatisfaction. The correlation between
      perceived discrimination and psychological distress was larger for White
      professional women than for Black professional women (White women odds ratio
      [OR]: 1.99; Black women OR: 0.80). A larger correlation between race and job
      dissatisfaction was observed for Black professional women than for Black non
      professional women. The racial composition of the workplace was unrelated to any
      of the outcomes. Study results emphasized the importance of decreasing the
      frequency of discrimination for positive mental health and underscored the need
      for more systematic research on discrimination and health among Black women of
      higher socioeconomic status, a growing sub-population in the United States. 

PMID- 24093453
TI  - Gender inequities in health: an exploratory qualitative study of Saudi women's
      perceptions.
AB  - This study aimed to explore Saudi Arabian women's perceptions of how gendered
      social structures affect their health by understanding their perceptions of these
      influences on their health relative to those on men's health. Qualitative
      methods, including focus group discussions (FGDs) and in-depth individual
      interviews (IDIs) were conducted with 66 married women in Riyadh, the capital
      city. Participants were purposively sampled for maximum variation, including
      consideration of socio-economic status, age, educational level, health status and
      the use of healthcare. The majority of women perceived their health to be worse
      than men's and attributed this to their childbearing, domestic and care-giving
      roles, restrictions on their mobility, poverty and psychological stress related
      to their responsibilities for children, and marital conflict. A minority of
      participants felt that men's health was worse than women's and related this to
      their gendered roles as "breadwinners," greater mobility and masculine norms and
      identities. Gender equity should be a health policy priority to improve women's
      health. 

PMID- 24093455
TI  - Zero-point tunneling splittings in compounds with multiple hydrogen bonds
      calculated by the rainbow instanton method.
AB  - Zero-point tunneling splittings are calculated, and the values are compared with
      the experimentally observed values for four compounds in which the splittings are
      due to multiple-proton transfer along hydrogen bonds. These compounds are three
      binary complexes, namely, the formic acid and benzoic acid dimer and the 2
      pyridone-2-hydroxypyridine complex, in which the protons move in pairs, and the
      calix[4]arene molecule, in which they move as a quartet. The calculations make
      use of and provide a test for the newly developed rainbow approximation for the
      zero-temperature instanton action which governs the tunneling splitting (as well
      as the transfer rate). This approximation proved to be much less drastic than the
      conventional adiabatic and sudden approximations, leading to a new general
      approach to approximate the instanton action directly. As input parameters the
      method requires standard electronic-structure data and the Hessians of the
      molecule or complex at the stationary configurations only; the same parameters
      also yield isotope effects. Compared to our earlier approximate instanton method,
      the rainbow approximation offers an improved treatment of the coupling of the
      tunneling mode to the other vibrations. Contrary to the conventional instanton
      approach based on explicit evaluation of the instanton trajectory, both methods
      bypass this laborious procedure, which renders them very efficient and capable of
      handling systems that thus far have not been handled by other theoretical
      methods. Past results for model systems have shown that the method should be
      valid for a wide range of couplings. The present results for real compounds show
      that it gives a satisfactory account of tunneling splittings and isotope effects
      in systems with strong coupling that enhances tunneling, thus demonstrating its
      applicability to low-temperature proton dynamics in systems with multiple
      hydrogen bonds. 

PMID- 24093454
TI  - Impaired endocytosis in proximal tubule from subchronic exposure to cadmium
      involves angiotensin II type 1 and cubilin receptors.
AB  - BACKGROUND: Chronic exposure to low cadmium (Cd) levels produces urinary
      excretion of low molecular weight proteins, which is considered the critical
      effect of Cd exposure. However, the mechanisms involved in Cd-induced proteinuria
      are not entirely clear. Therefore, the present study was designed to evaluate the
      possible role of megalin and cubilin (important endocytic receptors in proximal
      tubule cells) and angiotensin II type 1 (AT1) receptor on Cd-induced
      microalbuminuria. METHODS: Four groups of female Wistar rats were studied.
      Control (CT) group, vehicle-treated rats; LOS group, rats treated with losartan
      (an AT1 antagonist) from weeks 5 to 8 (10 mg/kg/day by gavage); Cd group, rats
      subchronically exposed to Cd (3 mg/kg/day by gavage) during 8 weeks, and Cd + LOS
      group, rats treated with Cd for 8 weeks and LOS from weeks 5-8. Kidney Cd
      content, glomerular function (evaluated by creatinine clearance and plasma
      creatinine), kidney injury and tubular function (evaluated by Kim-1 expression,
      urinary excretion of N-acetyl-beta-D-glucosaminidase (NAG) and glucose, and
      microalbuminuria), oxidative stress (measured by lipid peroxidation and NAD(P)H
      oxidase activity), mRNA levels of megalin, expressions of megalin and cubilin (by
      confocal microscopy) and AT1 receptor (by Western blot), were measured in the
      different experimental groups. Data were analyzed by one-way ANOVA or Kruskal
      Wallis test using GraphPad Prism 5 software (Version 5.00). P < 0.05 was
      considered statistically significant. RESULTS: Administration of Cd (Cd and Cd +
      LOS groups) increased renal Cd content. LOS-treatment decreased Cd-induced
      microalbuminuria without changes in: plasma creatinine, creatinine clearance,
      urinary NAG and glucose, oxidative stress, mRNA levels of megalin and cubilin,
      neither protein expression of megalin nor AT1 receptor, in the different
      experimental groups studied. However, Cd exposure did induce the expression of
      the tubular injury marker Kim-1 and decreased cubilin protein levels in proximal
      tubule cells whereas LOS-treatment restored cubilin levels and suppressed Kim-1
      expression. CONCLUSION: LOS treatment decreased microalbuminuria induced by Cd
      apparently through a cubilin receptor-dependent mechanism but independent of
      megalin.

PMID- 24093456
TI  - Costs of eye care services: prospective study from a faith-based hospital in
      Zambia.
AB  - PURPOSE: To estimate the mean costs of cataract surgery and refractive error
      correction at a faith-based eye hospital in Zambia. METHODS: Out-of-pocket
      expenses for user fees, drugs and transport were collected from 90 patient
      interviews; 47 received cataract surgery and 43 refractive error correction.
      Overhead and diagnosis-specific costs were determined from micro-costing of the
      hospital. Costs per patient were calculated as the sum of out-of-pocket expenses
      and hospital costs, excluding user fees to avoid double counting. RESULTS: From
      the perspective of the hospital, overhead costs amounted to US$31 per
      consultation and diagnosis-specific costs were US$57 for cataract surgery and
      US$36 for refractive error correction. When including out-of-pocket expenses,
      mean total costs amounted to US$128 (95% confidence interval [CI] US$96--168) per
      cataract surgery and US$86 (95% CI US$67--118) per refractive error correction.
      Costs of providing services corresponded well with the user fee levels
      established by the hospital. CONCLUSION: This is the first paper to report on the
      costs of eye care services in an African setting. The methods used could be
      replicated in other countries and for other types of visual impairments. These
      estimates are crucial for determining resources needed to meet global goals for
      elimination of avoidable blindness.

PMID- 24093457
TI  - The hydrophobic region of the DmsA twin-arginine leader peptide determines
      specificity with chaperone DmsD.
AB  - The system specific chaperone DmsD plays a role in the maturation of the
      catalytic subunit of dimethyl sulfoxide (DMSO) reductase, DmsA. Pre-DmsA contains
      a 45-amino acid twin-arginine leader peptide that is important for targeting and
      translocation of folded and cofactor-loaded DmsA by the twin-arginine
      translocase. DmsD has previously been shown to interact with the complete twin
      arginine leader peptide of DmsA. In this study, isothermal titration calorimetry
      was used to investigate the thermodynamics of binding between synthetic peptides
      composed of different portions of the DmsA leader peptide and DmsD. Only those
      peptides that included the complete and contiguous hydrophobic region of the DmsA
      leader sequence were able to bind DmsD with a 1:1 stoichiometry. Each of the
      peptides that were able to bind DmsD also showed some alpha-helical structure as
      indicated by circular dichroism spectroscopy. Differential scanning calorimetry
      revealed that DmsD gained very little thermal stability upon binding any of the
      DmsA leader peptides tested. Together, these results suggest that a portion of
      the hydrophobic region of the DmsA leader peptide determines the specificity of
      binding and may produce helical properties upon binding to DmsD. Overall, this
      study demonstrates that the recognition of the DmsA twin-arginine leader sequence
      by the DmsD chaperone shows unexpected rules and confirms further that the
      biochemistry of the interaction of the chaperone with their leaders demonstrates
      differences in their molecular interactions. 

PMID- 24093458
TI  - The impact of total parenteral nutrition support on pregnancy outcome in women
      with hyperemesis gravidarum.
AB  - OBJECTIVE: To assess pregnancy outcome among women with hyperemesis gravidarum
      (HEG) with and without total parenteral nutrition (TPN) support. STUDY DESIGN: A
      retrospective study of all pregnant women with singleton pregnancies who were
      hospitalized due to HEG between 1997 and 2011. Pregnancy outcome was compared
      with a control group without HEG matched by maternal age and parity in a 3:1
      ratio. RESULTS: Overall 599 women were admitted during the study period with the
      diagnosis of HEG and subsequently delivered in our center. Of those, 122 (20.4%)
      received TPN support. Women in the HEG group were characterized by a higher rate
      of severe preeclampsia (1.3% versus 0.5%, p = 0.04), and a higher rate of preterm
      delivery at less than 37 and 34 weeks (10.9% versus 6.9%, p < 0.001 and 4.7%
      versus 1.6%, p < 0.001, respectively). Neonates in the HEG group were
      characterized by a lower birth weight (3074 +/- 456 g versus 3248 +/- 543 g, p <
      0.001), higher rate of birth weight < 10th percentile (12.7% versus 6.8%, p <
      0.001), and a higher rate of neonatal morbidity (8.7% versus 3.8%, p < 0.001).
      These associations persisted after adjustment for potential confounders, and were
      of most notable among women with HEG who did not receive TPN support. CONCLUSION:
      HEG is an independent risk factor for adverse pregnancy outcome. TPN support
      during early pregnancy is associated with a decreased risk for perinatal
      morbidity.

PMID- 24093460
TI  - Sec-mediated secretion by Coxiella burnetii.
AB  - BACKGROUND: Coxiella burnetii is a Gram-negative intracellular bacterial pathogen
      that replicates within a phagolysosome-like parasitophorous vacuole (PV) of
      macrophages. PV formation requires delivery of effector proteins directly into
      the host cell cytoplasm by a type IVB secretion system. However, additional
      secretion systems are likely responsible for modification of the PV lumen
      microenvironment that promote pathogen replication. RESULTS: To assess the
      potential of C. burnetii to secrete proteins into the PV, we analyzed the protein
      content of modified acidified citrate cysteine medium for the presence of C.
      burnetii proteins following axenic (host cell-free) growth. Mass spectrometry
      generated a list of 105 C. burnetii proteins that could be secreted. Based on
      bioinformatic analysis, 55 proteins were selected for further study by expressing
      them in C. burnetii with a C-terminal 3xFLAG-tag. Secretion of 27 proteins by C.
      burnetii transformants was confirmed by immunoblotting culture supernatants.
      Tagged proteins expressed by C. burnetii transformants were also found in the
      soluble fraction of infected Vero cells, indicating secretion occurs ex vivo. All
      secreted proteins contained a signal sequence, and deletion of this sequence from
      selected proteins abolished secretion. These data indicate protein secretion
      initially requires translocation across the inner-membrane into the periplasm via
      the activity of the Sec translocase. CONCLUSIONS: C. burnetii secretes multiple
      proteins, in vitro and ex vivo, in a Sec-dependent manner. Possible roles for
      secreted proteins and secretion mechanisms are discussed.

PMID- 24093461
TI  - Migrant-friendly hospitals: a paediatric perspective--improving hospital care for
      migrant children.
AB  - BACKGROUND: The European Union (EU) Migrant-Friendly Hospital (MFH) Initiative,
      introduced in 2002, promotes the adoption of care approaches adapted to meet the
      service needs of migrants. However, for paediatric hospitals, no specific
      recommendations have been offered for MFH care for children. Using the Swiss MFH
      project as a case study, this paper aims to identify hospital-based care needs of
      paediatric migrants (PMs) and good service approaches. METHODS: Semi-structured
      interviews were conducted with principal project leaders of five paediatric
      hospitals participating in the Swiss MFH project. A review of the international
      literature on non-clinical hospital service needs and service responses of
      paediatric MFHs was conducted. RESULTS: Paediatric care can be complex, usually
      involving both the patient and the patient's family. Key challenges include
      differing levels of acculturation between parents and children; language
      barriers; cultural differences between patient and provider; and time
      constraints. Current service and infrastructural responses include interpretation
      services for PMs and parents, translated information material, and special
      adaptations to ensure privacy, e.g., during breastfeeding. Clear standards for
      paediatric migrant-friendly hospitals (P-MFH) are lacking. CONCLUSIONS:
      International research on hospital care for migrant children is scarce. The needs
      of paediatric migrants and their families may differ from guidance for adults.
      Paediatric migrant needs should be systematically identified and used to inform
      paediatric hospital care approaches. Hospital processes from admission to
      discharge should be revised to ensure implementation of migrant-sensitive
      approaches suitable for children. Staff should receive adequate support, such as
      training, easily available interpreters and sufficient consultation time, to be
      able to provide migrant-friendly paediatric services. The involvement of migrant
      groups may be helpful. Improving the quality of care for PMs at both policy and
      service levels is an investment in the future that will benefit native and
      migrant families.

PMID- 24093459
TI  - HLA-dependent tumour development: a role for tumour associate macrophages?
AB  - HLA abnormalities on tumour cells for immune escape have been widely described.
      In addition, cellular components of the tumour microenvironment, in particular
      myeloid derived suppressor cells (MDSC) and alternatively activated M2 tumour
      associated macrophages (TAMs), are involved in tumour promotion, progression,
      angiogenesis and suppression of anti-tumour immunity. However, the role of HLA in
      these activities is poorly understood. This review details MHC class I
      characteristics and describes MHC class I receptors functions. This analysis
      established the basis for a reflection about the crosstalk among the tumour
      cells, the TAMs and the cells mediating an immune response.The tumour cells and
      TAMs exploit MHC class I molecules to modulate the surrounding immune cells. HLA
      A, B, C and G molecules down-regulate the macrophage myeloid activation through
      the interaction with the inhibitory LILRB receptors. HLA A, B, C are able to
      engage inhibitory KIR receptors negatively regulating the Natural Killer and
      cytotoxic T lymphocytes function while HLA-G induces the secretion of pro
      angiogenic cytokines and chemokine thanks to an activator KIR receptor expressed
      by a minority of peripheral NK cells. The open conformer of classical MHC-I is
      able to interact with LILRA receptors described as being associated to the Th2
      type cytokine response, triggering a condition for the M2 like TAM polarization.
      In addition, HLA-E antigens on the surface of the TAMs bind the inhibitory
      receptor CD94/NKG2A expressed by a subset of NK cells and activated cytotoxic T
      lymphocytes protecting from the cytolysis.Furthermore MHC class II expression by
      antigen presenting cells is finely regulated by factors provided with
      immunological capacities. Tumour-associated macrophages show an epigenetically
      controlled down-regulation of the MHC class II expression induced by the decoy
      receptor DcR3, a member of the TNFR, which further enhances the M2-like
      polarization. BAT3, a positive regulator of MHC class II expression in normal
      macrophages, seems to be secreted by TAMs, consequently lacking its intracellular
      function, it looks like acting as an immunosuppressive factor.In conclusion HLA
      could cover a considerable role in tumour-development orchestrated by tumour
      associated macrophages. 

PMID- 24093462
TI  - The neuroanatomy of subthreshold depressive symptoms in Huntington's disease: a
      combined diffusion tensor imaging (DTI) and voxel-based morphometry (VBM) study.
AB  - BACKGROUND: Depressive symptoms are prominent psychopathological features of
      Huntington's disease (HD), making a negative impact on social functioning and
      well-being. METHOD: We compared the frequencies of a history of depression,
      previous suicide attempts and current subthreshold depression between 61 early
      stage HD participants and 40 matched controls. The HD group was then split based
      on the overall HD group's median Hospital Anxiety and Depression Scale-depression
      score into a group of 30 non-depressed participants (mean 0.8, s.d. = 0.7) and a
      group of 31 participants with subthreshold depressive symptoms (mean 7.3, s.d. =
      3.5) to explore the neuroanatomy underlying subthreshold depressive symptoms in
      HD using voxel-based morphometry (VBM) and diffusion tensor imaging (DTI).
      RESULTS: Frequencies of history of depression, previous suicide attempts or
      current subthreshold depressive symptoms were higher in HD than in controls. The
      severity of current depressive symptoms was also higher in HD, but not associated
      with the severity of HD motor signs or disease burden. Compared with the non
      depressed HD group DTI revealed lower fractional anisotropy (FA) values in the
      frontal cortex, anterior cingulate cortex, insula and cerebellum of the HD group
      with subthreshold depressive symptoms. In contrast, VBM measures were similar in
      both HD groups. A history of depression, the severity of HD motor signs or
      disease burden did not correlate with FA values of these regions. CONCLUSIONS:
      Current subthreshold depressive symptoms in early HD are associated with
      microstructural changes - without concomitant brain volume loss - in brain
      regions known to be involved in major depressive disorder, but not those
      typically associated with HD pathology.

PMID- 24093464
TI  - Ciprofloxacin 0.3% + dexamethasone 0.1% for the treatment for otitis media.
AB  - INTRODUCTION: Ciprofloxacin 0.3% with dexamethasone 0.1%
      (ciprofloxacin/dexamethasone) is an ototopical preparation for acute otitis
      externa, otorrhea with tympanostomy tubes, and is frequently used to treat
      chronic suppurative otitis media (CSOM). The advantage of topical therapy is the
      ability to deliver higher concentration of antibiotics to the treatment site when
      compared with oral or parenteral antibiotics. The delivery of a high
      concentration of antibiotics significantly decreases treatment failure and makes
      the development of resistant organisms unlikely. Previous ototopical preparations
      contained antibiotics such as aminoglycosides that are known to be ototoxic
      making treatment of otic infections without an intact tympanic membrane
      difficulty. AREAS COVERED: A literature search of PubMed was performed as the
      basis for a literature-based discussion on the clinical efficacy of
      ciprofloxacin/dexamethasone compared to oral antibiotics and ototopical therapy
      without a steroid component. The potential ototoxicity of ototopical therapies is
      discussed, including evidence demonstrating the lack of ototoxicity of
      fluoroquinolone and dexamethasone containing drops. EXPERT OPINION: Because
      multiple studies have demonstrated that fluoroquinolones are not ototoxic,
      fluoroquinolone ototopical drops should be a first-line treatment for otorrhea
      without an intact membrane. The addition of dexamethasone 0.1% to ciprofloxacin
      0.3% has been shown to decrease granulation tissue, improve clinical cure and
      achieve greater rates of bacterial eradication when compared to ciprofloxacin
      0.3% alone.

PMID- 24093463
TI  - Unraveling the redox properties of the global regulator FurA from Anabaena sp.
      PCC 7120: disulfide reductase activity based on its CXXC motifs.
AB  - Cyanobacterial FurA works as a global regulator linking iron homeostasis to
      photosynthetic metabolism and the responses to different environmental stresses.
      Additionally, FurA modulates several genes involved in redox homeostasis and
      fulfills the characteristics of a heme-sensor protein whose interaction with this
      cofactor negatively affects its DNA binding ability. FurA from Anabaena PCC 7120
      contains five cysteine residues, four of them arranged in two redox CXXC motifs.
      AIMS: Our goals were to analyze in depth the putative contribution of these CXXC
      motifs in the redox properties of FurA and to identify potential interacting
      partners of this regulator. RESULTS: Insulin reduction assays unravel that FurA
      exhibits disulfide reductase activity. Simultaneous presence of both CXXC
      signatures greatly enhances the reduction rate, although the redox motif
      containing Cys(101) and Cys(104) seems a major contributor to this activity.
      Disulfide reductase activity was not detected in other ferric uptake regulator
      (Fur) proteins isolated from heterotrophic bacteria. In vivo, FurA presents
      different redox states involving intramolecular disulfide bonds when is partially
      oxidized. Redox potential values for CXXC motifs, -235 and -238 mV, are
      consistent with those reported for other proteins displaying disulfide reductase
      activity. Pull-down and two-hybrid assays unveil potential FurA interacting
      partners, namely phosphoribulokinase Alr4123, the hypothetical amidase-containing
      domain All1140 and the DNA-binding protein HU. INNOVATION: A novel biochemical
      activity of cyanobacterial FurA based on its cysteine arrangements and the
      identification of novel interacting partners are reported. CONCLUSION: The
      present study discloses a putative connection of FurA with the cyanobacterial
      redox-signaling pathway.

PMID- 24093466
TI  - Endoscope-assisted spinal decompression surgery for lumbar spinal stenosis.
AB  - OBJECT: The authors undertook this study to document the clinical outcomes of
      microendoscopic laminotomy, a minimally invasive decompressive surgical technique
      using spinal endoscopy for lumbar decompression, in patients with lumbar spinal
      stenosis (LSS). METHODS: A total of 366 patients were enrolled in the study and
      underwent microendoscopic laminotomy between 2007 and 2010. Indications for
      surgery were single- or double-level LSS, persistent neurological symptoms, and
      failure of conservative treatment. Microendoscopy provided wide visualization
      through oblique lenses and allowed bilateral decompression via a unilateral
      approach, through partial resection of the base of the spinous process, thereby
      preserving the supraspinous and interspinous ligaments and contralateral
      musculature. Clinical symptoms and signs of low-back pain were evaluated prior to
      and following surgical intervention by applying the Japanese Orthopaedic
      Association (JOA) scoring system, Roland-Morris Disability Questionnaire (RMDQ),
      Japanese Orthopaedic Association Back Pain Evaluation Questionnaire (JOABPEQ),
      and 36-Item Short Form Health Survey (SF-36). These items were evaluated
      preoperatively and 2 years postoperatively. RESULTS: Effective circumferential
      decompression was achieved in all patients. The 2-year follow-up evaluation was
      completed for 310 patients (148 men and 162 women; mean age 68.7 years). The
      average recovery rate based on the JOA score was 61.3%. The overall results were
      excellent in 34.9% of the patients, good in 34.9%, fair in 21.7%, and poor in
      8.5%. The mean RMDQ score significantly improved from 11.3 to 4.8 (p < 0.001). In
      all categories of both JOABPEQ and SF-36, scores at 2 years' follow-up were
      significantly higher than those obtained before surgery (p < 0.001). Twelve
      surgery-related complications were identified: dural tear (6 cases [1.9%]), wrong
      level operation (1 [0.3%]), transient neuralgia (4 [1.3%]), and infection (1
      [0.3%]). All patients recovered, and there were no serious postoperative
      complications. CONCLUSIONS: Microendoscopic laminotomy is a safe and very
      effective minimally invasive surgical technique for the treatment of degenerative
      LSS.

PMID- 24093465
TI  - Clinical review: bleeding - a notable complication of treatment in patients with
      acute coronary syndromes: incidence, predictors, classification, impact on
      prognosis, and management.
AB  - This article focuses on the incidence, predictors, classification, impact on
      prognosis, and management of bleeding associated with the treatment of acute
      coronary syndrome. The issue of bleeding complications is related to the
      continual improvement of ischemic heart disease treatment, which involves mainly
      (a) the widespread use of coronary angiography, (b) developments in percutaneous
      coronary interventions, and (c) the introduction of new antithrombotics. Bleeding
      has become an important health and economic problem and has an incidence of 2.0%
      to 17%. Bleeding significantly influences both the short- and long-term
      prognoses. If a group of patients at higher risk of bleeding complications can be
      identified according to known risk factors and a risk scoring system can be
      developed, we may focus more on preventive measures that should help us to reduce
      the incidence of bleeding. 

PMID- 24093467
TI  - A novel device to simplify intraoperative radiographic visualization of the
      cervical spine by producing transient caudal shoulder displacement: a 2-center
      case series of 80 patients.
AB  - OBJECT: Intraoperative radiographic localization within the cervical spine can be
      a challenge because of the anatomical relation of the musculoskeletal structures
      of the pectoral girdle. On standard cross-table lateral radiographs, these
      structures can produce shadowing that obscure the anatomical features of the
      cervical vertebrae, particularly at the caudal levels. Surgical guidelines
      recommend accurate intraoperative localization as a means to reduce wrong-level
      spine surgery, and unobstructed visualization is needed for fluoroscopy-guided
      placement of spinal instrumentation. In this article, the authors describe and
      evaluate a novel device designed to provide transient intraoperative caudal
      displacement of the shoulders to improve and simplify radiographic visualization
      of the cervical spine. METHODS: A 2-center prospective study was conducted to
      evaluate the device. The study included a total of 80 patients undergoing
      cervical spine surgery. The device was evaluated in a cohort of 50 patients
      undergoing elective single-level anterior discectomy and fusion and also in a
      second cohort of 30 patients at an independent institution. The patients in this
      second cohort were undergoing a variety of cervical spine procedures for multiple
      indications and were included in the study to allow the authors to assess the
      effectiveness of the device in a general neurosurgical practice. After the
      patients were anesthetized and positioned, consecutive standard cross-table
      lateral radiographs or intraoperative fluoroscopic were obtained before and after
      use of the device. The images were compared in order to determine the difference
      in lowest vertebral level visible. RESULTS: There was an average difference in
      cervical spine visualization of +2.8 +/- 0.9 vertebral levels in the first
      cohort, while in the second the improvement was +1.2 +/- 0.7 levels (p < 0.0001
      between cohorts, unpaired t-test). There was one complication, a minor shoulder
      abrasion, which required no specific management. CONCLUSIONS: This device is safe
      and effective for increasing the radiographic visualization of the cervical spine
      for intraoperative localization.

PMID- 24093468
TI  - Spinal intradural cystic venous angioma originating from a nerve root in the
      cauda equina.
AB  - A spinal intradural extramedullary venous angioma is extremely rare and has not
      been previously reported. In this paper, the authors report on this entity with
      morphological and immunohistochemical evidence, and discuss the surgical strategy
      for its treatment. A 54-year-old woman presented to Nagoya University Hospital
      complaining of left-sided pain in the hip, thigh, and inguinal and perianal
      regions, with progressive worsening during the previous 2 weeks. Lumbar spine MRI
      showed an intradural extramedullary cyst at the level of T12-L1, which extended
      from the conus medullaris to the cauda equina. The cyst wall was not enhanced on
      T1-weighted MRI with Gd. Intraoperatively, a midline dural opening allowed the
      authors to easily visualize a dark-reddish cyst behind the spinal nerve rootlets
      in the cauda equina adjacent to the conus medullaris. The cyst was believed to
      originate from one of the spinal nerve rootlets in the cauda equina and a cluster
      of veins was identified on the cyst wall. The cyst was resected with the affected
      nerve rootlet. The surgery left no detectable neurological deficit. Based on the
      morphological and immunohistochemical evidence, the lesion was diagnosed as a
      venous angioma. No tumor recurrence was confirmed based on MRI at the time of the
      2-year follow up. This is the first report of an intradural extramedullary cystic
      venous angioma that was successfully resected. 

PMID- 24093469
TI  - Bee venom treatment for refractory postherpetic neuralgia: a case report.
AB  - OBJECTIVE: Bee venom has been reported to have antinociceptive and anti
      inflammatory effects in experimental studies. However, questions still remain
      regarding the clinical use of bee venom. This report describes the successful
      outcome of bee venom treatment for refractory postherpetic neuralgia. PATIENT: A
      72-year-old Korean man had severe pain and hypersensitivity in the region where
      he had developed a herpes zoster rash 2 years earlier. He was treated with
      antivirals, painkillers, steroids, and analgesic patches, all to no effect.
      INTERVENTION: The patient visited the East-West Pain Clinic, Kyung Hee University
      Medical Center, to receive collaborative treatment. After being evaluated for bee
      venom compatibility, he was treated with bee venom injections. A 1:30,000 diluted
      solution of bee venom was injected subcutaneously along the margins of the rash
      once per week for 4 weeks. RESULTS: Pain levels were evaluated before every
      treatment, and by his fifth visit, his pain had decreased from 8 to 2 on a 10
      point numerical rating scale. He experienced no adverse effects, and this
      improvement was maintained at the 3-month, 6-month, and 1-year phone follow-up
      evaluations. CONCLUSION: Bee venom treatment demonstrates the potential to become
      an effective treatment for postherpetic neuralgia. Further large-sample clinical
      trials should be conducted to evaluate the overall safety and efficacy of this
      treatment.

PMID- 24093472
TI  - ESBL, plasmidic AmpC, and associated quinolone resistance determinants in
      coliforms isolated from hospital effluent: first report of qnrB2, qnrB9, qnrB19,
      and blaCMY-4 in Algeria.
AB  - The characterization of extended-spectrum beta-lactamases , plasmidic AmpC
      (pAmpC), and associated plasmid-mediated quinolone resistance (PMQR) determinants
      in cefotaxime-resistant coliforms isolated from hospital effluent in Algiers
      showed blaCTX-M genes in 89%, blaTEM-1 in 79.8%, and pAmpC genes (blaCIT) in 2.7%
      isolates. Association of ISEcp1B with blaCTX-M was found in all CTX-M+ isolates,
      and 97.2% harboured class 1 integrons. Sequencing showed blaCTX-M-15, blaCTX-M-3,
      and blaCMY-4 genes. blaCTX-M-3 and blaCTX-M-15 were located in Inc L/M
      conjugative plasmids. The PMQR determinants identified were qnrB1, qnrB2, qnrB9,
      qnrB19, qnrS2, and aac(6')-Ib-cr. qnrB2, qnrB9, qnrB19, and blaCMY-4 are
      described for the first time in Algeria and qnrB19 for the first time in non
      clinical environments. This study highlights the major potential role of hospital
      effluents as providers of resistance genes to natural environments. 

PMID- 24093473
TI  - How the bicyclo[4.1.0] substrate isomerizes into 4,5-dihydrobenzo[b]furan: the
      contribution from W(CO)5 and NEt3.
AB  - The cycloisomerization of a bicyclo[4.1.0] substrate into 4,5
      dihydrobenzo[b]furan was investigated by using density functional theory (DFT).
      Comparative studies on four models (model I: with W(CO)5 and NEt3; model II:
      without NEt3; model III: without W(CO)5; model IV: without W(CO)5 and NEt3)
      indicate that this reaction is the most likely to proceed under model I to give
      the product. The ring closure process is greatly associated with the H1 and H2
      transfer processes, because in the H1 transfer process, the carbene C3 atom is
      mainly stabilized by W(CO)5, and in the H2 atom transfer process the C3 atom is
      mainly stabilized by the O1 atom. The rearrangement of 12 to give 14 is the rate
      determining step of this reaction with a free energy barrier of 31.0 kcal/mol.
      The presence of W(CO)5 can not only promote the H1 transfer and the ring closure
      (1->6-[W]) but can also be slightly favorable for the isomerization of 6-[W] into
      11-[W](6-[W]->11-[W]). NEt3 mainly has an effect in the 6-[W]->11-[W] stage, in
      which it mainly plays proton-transfer bridge and proton-adsorption roles. 

PMID- 24093475
TI  - Magnetic polarons and large negative magnetoresistance in GaAs nanowires
      implanted with Mn ions.
AB  - We report on low-temperature magnetotransport and SQUID measurements on heavily
      doped Mn-implanted GaAs nanowires. SQUID data recorded at low magnetic fields
      exhibit clear signs of the onset of a spin-glass phase with a transition
      temperature of about 16 K. Magnetotransport experiments reveal a corresponding
      peak in resistance at 16 K and a large negative magnetoresistance, reaching 40%
      at 1.6 K and 8 T. The negative magnetoresistance decreases at elevated
      temperatures and vanishes at about 100 K. We interpret our transport data in
      terms of spin-dependent hopping in a complex magnetic nanowire landscape of
      magnetic polarons, separated by intermediate regions of Mn impurity spins,
      forming a paramagnetic/spin-glass phase. 

PMID- 24093474
TI  - Scaffold properties are a key determinant of the size and shape of self-assembled
      virus-derived particles.
AB  - Controlling the geometry of self-assembly will enable a greater diversity of
      nanoparticles than now available. Viral capsid proteins, one starting point for
      investigating self-assembly, have evolved to form regular particles. The
      polyomavirus SV40 assembles from pentameric subunits and can encapsidate anionic
      cargos. On short ssRNA (<=814 nt), SV40 pentamers form 22 nm diameter capsids. On
      RNA too long to fit a T = 1 particle, pentamers forms strings of 22 nm particles
      and heterogeneous particles of 29-40 nm diameter. However, on dsDNA SV40 forms 50
      nm particles composed of 72 pentamers. A 7.2-A resolution cryo-EM image
      reconstruction of 22 nm particles shows that they are built of 12 pentamers
      arranged with T = 1 icosahedral symmetry. At 3-fold vertices, pentamers each
      contribute to a three-helix triangle. This geometry of interaction is not seen in
      crystal structures of T = 7 viruses and provides a structural basis for the
      smaller capsids. We propose that the heterogeneous particles are actually mosaics
      formed by combining different geometries of interaction from T = 1 capsids and
      virions. Assembly can be trapped in novel conformations because SV40
      interpentamer contacts are relatively strong. The implication is that by virtue
      of their large catalog of interactions, SV40 pentamers have the ability to self
      assemble on and conform to a broad range of shapes. 

PMID- 24093476
TI  - Job insecurity during recessions: effects on survivors' work stress.
AB  - BACKGROUND: Previous studies show a variety of negative health consequences for
      the remaining workforce after downsizing events. This study examined self
      reported work stress from 2009-2012 in the context of a large multi-site aluminum
      manufacturing company that underwent severe downsizing in 2009. METHODS: This
      study examined the association between work stress and working at a work site
      that underwent severe downsizing. We assessed the level of downsizing across
      thirty plants in 2009 and categorized seven as having undergone severe
      downsizing. We linked plant-level downsizing information to individual workers'
      responses to an annual work engagement survey, which included three work stress
      questions. From 2009 to 2012 over 14, 000 employees were asked about their
      experience of work stress. Though the surveys were anonymous, the surveys
      captured employees' demographic and employment characteristic as well as plant
      location. We used hierarchical logistic regressions to compare responses of
      workers at severely downsized plants to workers at all other plant while
      controlling for demographic and plant characteristics. Responses to the work
      stress questions and one control question were examined. RESULTS: In all yearly
      surveys salaried workers consistently reported having more work stress than
      hourly workers. There was no differential in work stress for workers at severely
      downsized plants in 2009. In 2010 to 2012, salaried workers who remained at
      severely downsized plants reported significantly higher work stress than salaried
      workers at all other plants across multiple work stress questions. Examination of
      the 2006 survey confirmed that there were no pre-existing differences in work
      stress among salaried employees working at plants that would eventually
      experience severe downsizing. In addition, there was no difference in responses
      to the control question at severely downsized plants. CONCLUSION: Salaried
      workers at plants with high layoffs experienced more work stress after 2009 than
      their counterparts at non-high layoff plants. Increased work stress is important
      to monitor and may be a mediating pathway through which the external economic
      environment leads to adverse health outcomes.

PMID- 24093478
TI  - Precipitous intussusception with anal protrusion and complete overt rectal
      prolapse presenting with intestinal obstruction and an associated rectal adenoma
      in a young man: a case report.
AB  - BACKGROUND: Intestinal obstruction secondary to intussusception, occurring
      simultaneously with complete rectal prolapse, is an unusual entity among young
      adults. When it occurs the intussusceptum may protrude per anus. Few cases are
      cited in literature; each with a unique clinical presentation. There is
      apparently no uniform trend in its clinical and pathological picture. CASE
      PRESENTATION: A 38-year-old, African-Ugandan man presented with sudden occurrence
      of rectal prolapse for one day. He had otherwise been in good health. Symptoms
      were precipitous. A clinical diagnosis of intussusception of the lower gut with
      rectal prolapse, and intestinal obstruction, was made. The intussusception was
      found to have a polyp as the 'lead point'. He was treated by manual reduction of
      the intussusception and the prolapse under general anesthesia. Histopathologic
      examination of the polyp showed it to be an adenoma. Definitive surgical
      treatment of the patient was not completed due to socioeconomic challenges.
      CONCLUSIONS: Rectal prolapse and intussusception are commonly childhood
      conditions. Rectal prolapse alone is commoner in the middle-aged and elderly;
      females in particular. The finding of this combined clinical entity in a young,
      adult male is therefore a unique condition with an unusual presentation. It is
      the first case of its kind reported in East Africa. It is also an example of an
      adenoma constituting a 'lead point' for an intussusception at the
      gastrointestinal tract's terminus. Even in the presence of a pre-existing
      adenoma, a relatively common lesion, other differential diagnoses acting as 'lead
      points' ought to be considered in perspective. This characteristic, along with
      other features described in this case, is useful knowledge for colorectal
      surgeons, general surgeons, gastrointestinal pathologists, and
      gastroenterologists given their involvement in the diagnosis and management of
      anorectal disease of peculiar presentation.

PMID- 24093479
TI  - Investigating the ruthenium metalation of proteins: X-ray structure and Raman
      microspectroscopy of the complex between RNase A and AziRu.
AB  - A Raman-assisted crystallographic study on the adduct between AziRu, a Ru(III)
      complex with high antiproliferative activity, and RNase A is presented. The
      protein structure is not perturbed significantly by the Ru label. The metal
      coordinates to ND atoms of His105 or of His119 imidazole rings, losing all of its
      original ligands but retaining octahedral, although distorted, coordination
      geometry. The AziRu binding inactivates the enzyme, suggesting that its antitumor
      action can be exerted by a mechanism of competitive inhibition. 

PMID- 24093477
TI  - Comparative efficacy of long-acting bronchodilators for COPD: a network meta
      analysis.
AB  - BACKGROUND: Clinicians are faced with an increasingly difficult choice regarding
      the optimal bronchodilator for patients with chronic obstructive pulmonary
      disease (COPD) given the number of new treatments. The objective of this study is
      to evaluate the comparative efficacy of indacaterol 75/150/300 MUg once daily
      (OD), glycopyrronium bromide 50 MUg OD, tiotropium bromide 18 MUg/5 MUg OD,
      salmeterol 50 MUg twice daily (BID), formoterol 12 MUg BID, and placebo for
      moderate to severe COPD. METHODS: Forty randomized controlled trials were
      combined in a Bayesian network meta-analysis. Outcomes of interest were trough
      and post-dose forced expiratory volume in 1 second (FEV1), St. George's
      Respiratory Questionnaire (SGRQ) score and responders (>=4 points), and
      Transition Dyspnea Index (TDI) score and responders (>=1 point) at 6 months.
      RESULTS: Indacaterol was associated with a higher trough FEV1 than other active
      treatments (difference for indacaterol 150 MUg and 300 MUg versus placebo: 152 mL
      (95% credible interval (CrI): 126, 179); 160 mL (95% CrI: 133, 187)) and the
      greatest improvement in SGRQ score (difference for indacaterol 150 MUg and 300
      MUg versus placebo: -3.9 (95% CrI -5.2, -2.6); -3.6 (95% CrI -4.8, -2.3)).
      Glycopyrronium and tiotropium 18 MUg resulted in the next best estimates for both
      outcomes with minor differences (difference for glycopyrronium versus tiotropium
      for trough FEV1 and SGRQ: 18 mL (95% CrI: -16, 51); -0.55 (95% CrI: -2.04, 0.92).
      CONCLUSION: In terms of trough FEV1 and SGRQ score indacaterol, glycopyrronium,
      and tiotropium are expected to be the most effective bronchodilators.

PMID- 24093480
TI  - Efficient near-UV emitters based on cationic bis-pincer iridium(III) carbene
      complexes.
AB  - We report on the photophysical studies of two cationic near-UV emitters based on
      bis-pincer Ir(III) carbene complexes: [Ir(nBu)(C(NHC)(Me)CC(NHC))2]X, where
      Ir(nBu)(C(NHC)(Me)CC(NHC)) is (4,6-dimethyl-1,3-phenylene-kappaC(2))bis(1
      butylimidazol-2-ylidene) and X = I(-) or PF6(-)). The compounds are highly
      emitting in deaerated CH3CN solution with emission maxima at 384 and 406 nm, and
      photoluminescence quantum yields of 0.41 and 0.38, for
      [Ir(nBu)(C(NHC)(Me)CC(NHC))2]I and Ir(nBu)(C(NHC)(Me)CC(NHC))2]PF6, respectively.
      In order to gain deeper understandings into their structural and electronic
      features, as well as to ascertain the nature of the excited states involved into
      the electronic absorption processes, density functional theory (DFT) and time
      dependent DFT (TD-DFT) calculations have been performed on the ground and excited
      states of the closely related complex [Ir(Me)(C(NHC)(Me)CC(NHC))2](+). In the
      solid state, an emission at low energy is observed (lambda(max) = 500 nm) for
      both complexes. However, the intensity of the emission at high energy versus the
      intensity of the new emission at low energy is dependent on the nature of
      counterions. The origin of this emission is not completely clear, but the
      experimental data point to the formation of trapping sites induced by aggregation
      processes involving the interaction between the cationic emitter and the
      counterion.

PMID- 24093481
TI  - Hybrid bimetallic metal-organic frameworks: modulation of the framework stability
      and ultralarge CO2 uptake capacity.
AB  - A series of isostructural hybrid bimetallic metal-organic frameworks (MOFs),
      Ni(x)M(1-x)-ITHDs [M = Zn(II), Co(II)], have been prepared via a conventional
      solvothermal reaction in the presence of varying mole ratios of Ni(II)/Zn(II) or
      Ni(II)/Co(II) mixed metal ions. While a critical amount of the doped Ni(II) ion
      (more than ~0.2 mol fraction) is needed to have any enhancement of the framework
      stability of the hybrid bimetallic NixZn1-x-ITHDs, even a very small amount of
      the doped Ni(II) ion (~0.1 mol fraction) produced a full enhancement of the
      framework stability of the hybrid bimetallic Ni(x)Co(1-x)-ITHDs. The highly
      porous and rigid Ni(x)Co(1-x)-ITHDs activated via a conventional vacuum drying
      process shows a Brunauer-Emmett-Teller specific surface area of 5370 m(2) g(-1),
      which is comparable to that of pure Ni-ITHD. The CO2 uptake capacities of Ni-ITHD
      and Ni(0.11)Co(0.89)-ITHD (2.79 and 2.71 g g(-1), respectively) at 1 bar and 195
      K are larger than those of any other reported MOFs under similar conditions and
      the excess CO2 uptake capacity at 40 bar and 295 K (~1.50 g g(-1)) is comparable
      to those of other MOFs, which are activated via the supercritical carbon dioxide
      drying process, with similar pore volumes.

PMID- 24093482
TI  - Synthesis and characterization of heterobimetallic (Pd/B) Nindigo complexes and
      comparisons to their homobimetallic (Pd2, B2) analogues.
AB  - Reactions of Nindigo-BF2 complexes with Pd(hfac)2 produced mixed complexes with
      Nindigo binding to both a BF2 and a Pd(hfac) unit. These complexes are the first
      in which the Nindigo ligand binds two different substrates, and provide a
      conceptual link between previously reported bis(BF2) and bis(Pd(hfac)) complexes.
      The new Pd/B complexes have intense near IR absorption near 820 nm, and they
      undergo multiple reversible oxidations and reductions as probed by cyclic
      voltammetry experiments. The spectral, redox, and structural properties of these
      complexes are compared against those of the corresponding B2 and Pd2 complexes
      with the aid of time-dependent density functional calculations. In all cases the
      low-energy electronic transitions are ligand-centered pi-pi* transitions, but the
      highest occupied molecular orbital (HOMO) and lowest unoccupied molecular orbital
      (LUMO) energies--and hence the absorption wavelength as well as the oxidation and
      reduction potentials--are significantly modulated by the moieties bound to the
      Nindigo ligand.

PMID- 24093483
TI  - 3d early transition metal complexes supported by a new sterically demanding
      aryloxide ligand.
AB  - The bulky aryloxide 2,6-bis(diphenylmethyl)-4-tert-butylphenol [HOAr(tBu)] (1)
      can be synthesized from 4-tert-butylphenol and benzhydrol in solvent-free
      conditions and obtained pure in 91% yield. Deprotonation of HOAr(tBu) is
      accomplished with M(N(SiMe3)2) (M = Na, Li), yielding the corresponding salts of
      the aryloxide [MOAr(tBu)] (M(+) = Na (2), Li(3)) in 83% and 73% yield,
      respectively. Facile salt formation of the aryloxide ligand allows for
      transmetalation to a variety of metal halides. Through transmetalation reactions
      involving two aryloxides, mononuclear complexes of the type
      [M'(OAr(tBu))2Cl(THF)2] (M' = Sc (4), V (5), Cr (6), Ti (7)) can be prepared from
      the corresponding metal halide precursor MCl3(THF)3. Additionally, two aryloxides
      can be coordinated to Ti(IV) via a protonolysis route of Ti(NMe2)2Cl2 and 2 equiv
      of HOAr(tBu) to yield [Ti(OAr(tBu))2Cl2(NHMe2)] (8) in 72% isolated yield. Single
      crystal X-ray diffraction studies of 1, 2, and the 3d metal complexes 5-8 clearly
      show the steric demand of the bulky ligand, whereas in transition metal complexes
      we do not observe the formation of mononuclear tris-aryloxide complexes. 

PMID- 24093484
TI  - "Click" star-shaped and dendritic PEGylated gold nanoparticle-carborane
      assemblies.
AB  - Carboranes that have a high boron content are key materials for boron neutron
      capture therapy (BNCT), while PEGylated gold nanoparticles (AuNPs) are also most
      useful in various aspects of nanomedicine including photothermotherapy, imaging
      and drug vectorization. Therefore, methods to assemble these key components have
      been investigated for the first time. Strategies and results are delineated in
      this article, and the nanomaterials have been characterized using transmission
      electron microscopy (TEM), dynamic light scattering (DLS), UV-vis., mass and
      multinuclear NMR data. A series of well-defined water-soluble bifunctional AuNPs
      containing carborane and polyethylene glycol (PEG) were synthesized through
      either two-step Cu(I)-catalyzed azide-alkyne cycloaddition CuAAC ("click")
      reactions at the periphery of azido-terminated AuNPs in the presence of the
      efficient catalyst [Cu(I)tren(CH2Ph)6][Br] or simply by direct stabilization of
      AuNPs using a tris-carborane thiol dendron or a hybrid dendron containing both
      PEG and carborane. 

PMID- 24093485
TI  - Specific interaction between uranium anionic complexes and the cations of
      bis(trifluoromethylsulfonyl)imide based ionic liquids.
AB  - The redox properties of uranium(IV) hexachloro complex have been investigated
      with a glassy carbon electrode in four bis(trifluoromethylsulfonyl)imide (Tf2N(
      )) based ionic liquids (ILs): the 1-butyl-3-methylimidazolium ([BuMeIm](+)), the
      1-butyl-2,3-dimethylimidazolium ([BuMe2Im](+)), the N-butylmethylpyrrolidinium
      ([BuMePyr](+)), and the tributyl-methylammonium ([MeBu3N](+)). The cyclic
      voltammetric analysis has revealed two main redox systems: U(V)Cl6(-)/U(IV)Cl6(2
      ) around 0.2 V and U(IV)Cl6(2-)/U(III)Cl6(3-) around -2 V. The formation of
      U(V)Cl6(-), a non-dioxo uranium(V) species, can then be observed at the electrode
      in [Tf2N](-) based ILs. This work also provides evidence of a specific
      interaction between the uranium anionic species and the IL cations because the
      standard potentials of both redox couples depend on the IL. The interaction
      extent has been evaluated by comparison of the IL cation number associated with
      the uranium anionic complex. For that purpose, the standard potentials of both
      systems have been measured in the less interacting medium [MeBu3N][Tf2N] as a
      function of the [BuMeIm](+), [BuMe2Im](+), and [BuMePyr](+) concentration.
      Predominance diagrams for uranium hexachloro complexes, analogous to the Pourbaix
      diagram, have then been built in [MeBu3N][Tf2N] depending on the IL cations
      concentration. The exploitation of these diagrams leads to the conclusion that
      the interaction is function of the charge of the uranium hexachloro complex
      (U(V)Cl6(-) < U(IV)Cl6(2-) < U(III)Cl6(3-)) and the IL cation ([BuMe2Im](+) <
      [BuMePyr](+) < [BuMeIm](+)). The influence of the IL cation could be correlated
      to the size and the electropositivity of the IL cation. The association would
      occur by H-bonding and electrostatic interaction. Ab initio calculations were
      also carried out to evaluate the strength of the interaction between the anionic
      uranium(IV) chloro complex and the IL cations. The results show that [BuMeIm](+)
      interacts the most and [MeBu3N](+) the least with U(IV)Cl6(2-), and the magnitude
      of the interaction is comparable for [BuMe2Im](+) and [BuMePyr](+). 

PMID- 24093486
TI  - The solid solution series (GeTe)x(LiSbTe2)2 (1 <= x <= 11) and the thermoelectric
      properties of (GeTe)11(LiSbTe2)2.
AB  - Exchanging one Ge(2+) with two Li(+) per formula unit in (GeTe)n(Sb2Te3) (n = 1,
      2, 3, ...) eliminates cation vacancies, because it leads to an equal number of
      cations and anions. This substitution results in the solid solution
      (GeTe)x(LiSbTe2)2 (with x = n - 1, but n not necessarily an integer). For x < 6,
      these stable compounds crystallize in a rock-salt-type structure with random
      cation disorder. Neutron data show that a small fraction of Ge occupies
      tetrahedral voids for x = 2 and 3. For x > 6, (GeTe)x(LiSbTe2)2 forms a GeTe-type
      structure that shows a phase transition to a cubic high-temperature phase at ca.
      280  degrees C. The thermoelectric properties of (GeTe)11(LiSbTe2)2 have been
      investigated and show that this compound is a promising thermoelectric material
      with a ZT value of 1.0 at 450  degrees C. The high ZT value of the
      thermodynamically stable compound is caused by a low phononic contribution to the
      thermal conductivity; probably, Li acts as a "pseudo-vacancy". 

PMID- 24093487
TI  - The association of very-low-density lipoprotein with ankle-brachial index in
      peritoneal dialysis patients with controlled serum low-density lipoprotein
      cholesterol level.
AB  - BACKGROUND: Peripheral artery disease (PAD) represents atherosclerotic disease
      and is a risk factor for death in peritoneal dialysis (PD) patients, who tend to
      show an atherogenic lipid profile. In this study, we investigated the
      relationship between lipid profile and ankle-brachial index (ABI) as an index of
      atherosclerosis in PD patients with controlled serum low-density lipoprotein
      (LDL) cholesterol level. METHODS: Thirty-five PD patients, whose serum LDL
      cholesterol level was controlled at less than 120 mg/dl, were enrolled in this
      cross-sectional study in Japan. The proportions of cholesterol level to total
      cholesterol level (cholesterol proportion) in 20 lipoprotein fractions and the
      mean size of lipoprotein particles were measured using an improved method,
      namely, high-performance gel permeation chromatography. Multivariate linear
      regression analysis was adjusted for diabetes mellitus and cardiovascular and/or
      cerebrovascular diseases. RESULTS: The mean (standard deviation) age was 61.6
      (10.5) years; PD vintage, 38.5 (28.1) months; ABI, 1.07 (0.22). A low ABI (0.9 or
      lower) was observed in 7 patients (low-ABI group). The low-ABI group showed
      significantly higher cholesterol proportions in the chylomicron fraction and
      large very-low-density lipoproteins (VLDLs) (Fractions 3-5) than the high-ABI
      group (ABI>0.9). Adjusted multivariate linear regression analysis showed that ABI
      was negatively associated with serum VLDL cholesterol level (parameter estimate=
      0.00566, p=0.0074); the cholesterol proportions in large VLDLs (Fraction 4,
      parameter estimate=-3.82, p=0.038; Fraction 5, parameter estimate=-3.62,
      p=0.0039) and medium VLDL (Fraction 6, parameter estimate=-3.25, p=0.014); and
      the size of VLDL particles (parameter estimate=-0.0352, p=0.032). CONCLUSIONS:
      This study showed that the characteristics of VLDL particles were associated with
      ABI among PD patients. Lowering serum VLDL level may be an effective therapy
      against atherosclerosis in PD patients after the control of serum LDL cholesterol
      level.

PMID- 24093488
TI  - Autosomal-dominant Leber Congenital Amaurosis Caused by a Heterozygous CRX
      Mutation in a Father and Son.
AB  - BACKGROUND: Leber congenital amaurosis (LCA) is most often an autosomal recessive
      disorder. We report a father and son with autosomal dominant LCA due to a
      mutation in the CRX gene. MATERIALS AND METHODS: DNA screening using an allele
      specific assay of 90 of the most common LCA-causing variations in the coding
      sequences of AIPL1, CEP290, CRB1, CRX, GUCY2D, RDH12 and RPE65 was performed on
      the father. Automated DNA sequencing of his son examining exon 3 of the CRX gene
      was subsequently performed. RESULTS: Both father and son have a heterozygous
      single base pair deletion of an adenine at codon 153 in the coding sequence of
      the CRX gene resulting in a frameshift mutation. CONCLUSION: Mutations involving
      the CRX gene may demonstrate an autosomal dominant inheritance pattern for LCA.

PMID- 24093489
TI  - The evaluation of rapid cooling as an anesthetic method for the zebrafish.
AB  - As zebrafish became a popular research system in contemporary biomedical
      research, effective anesthesia, which had low toxicity and high efficacy, was
      needed. The objective of this article was to evaluate the anesthetic effect of
      rapid cooling for embryo and larvae zebrafish with ice slush (ice and water
      admixture). The time to stage 5 anesthesia and maintaining for more than 5 s were
      detected and compared to MS-222 anesthesia. Besides, the time of recovery from
      anesthesia, mortality, and the survivability were measured and compared with MS
      222 anesthesia. The results showed that anesthesia was generally achieved within
      10 s for rapid cooling, which was more rapid than MS-222. The survivability assay
      demonstrated that rapid cooling was suitable for embryo and larvae zebrafish (1
      14 days) and could be used for repeated anesthesia. The most important advantage
      was that this anesthesia could persist for 10 min and had no mortality. These
      findings suggested that rapid cooling provided advantages of improved safety,
      rapid anesthesia, and potentially low mortality rates and could be an effective
      anesthetic method for scientific research.

PMID- 24093490
TI  - Does increased peripheral C-reactive protein predate the occurrence of a short
      cervical length?
AB  - OBJECTIVE: Shortened cervical length is an important predictor of preterm birth,
      though the etiology of cervical length variation has not been fully elucidated.
      Our objective was to evaluate the potential association between peripheral C
      reactive protein (CRP), a first trimester peripheral marker of inflammation, and
      second trimester decreased cervical length. METHODS: Cases and controls were
      defined by second trimester cervical length >/<25 mm. CRP concentrations were
      measured in archived first trimester screen serum via commercial assay. The
      association between CRP and cervical length was evaluated via Wilcoxon's rank
      test. Both logistic and linear regressions were performed. RESULTS: A total of 49
      cases were matched to 98 controls. No statistically significant difference in
      first trimester CRP was demonstrated between cases and controls overall. Among
      subjects with decreased cervical lengths, however, there was a significant linear
      association between the degree of shortening and first trimester CRP
      concentrations (p = 0.022). CONCLUSION: First trimester CRP was not associated
      with decreased second trimester cervical length overall. However, the degree of
      shortening correlated with increased first trimester CRP concentrations in
      patients with a short cervix. This suggests that systemic inflammation in early
      pregnancy may underlie variation in second trimester cervical lengths among
      higher risk individuals.

PMID- 24093491
TI  - Predictive theory for the addition and insertion kinetics of 1CH2 reacting with
      unsaturated hydrocarbons.
AB  - The reactions of singlet methylene, (1)CH2, with unsaturated hydrocarbons are of
      considerable significance to the formation and growth of polycyclic aromatic
      hydrocarbons (PAHs). In this work, we employ high level ab initio transition
      state theory to predict the high pressure rate coefficient for singlet methylene
      reacting with acetylene (C2H2), ethylene (C2H4), propyne (CH3CCH), propene
      (CH3CHCH2), allene (CH2CCH2), 1,3-butadiene (CH2CHCHCH2), 2-butyne (CH3CCCH3),
      and benzene (C6H6). Both addition and insertion channels are found to contribute
      significantly to the kinetics, with the insertion kinetics of increasing
      importance for larger hydrocarbons due to the increasing number of CH bonds and
      increasingly attractive interactions. We treat the addition kinetics with direct
      CASPT2 based variable-reaction-coordinate transition state theory. One
      dimensional corrections to the CASPT2 interaction energies are obtained from
      geometry relaxation calculations and CCSD(T)/CBS evaluations. The insertion
      kinetics is treated with traditional variational TST methods employing
      CCSD(T)/CBS energies obtained along the CASPT2/cc-pVTZ distinguished coordinate
      reaction paths. The overall rate constant and branching fractions are obtained
      from a multiple transition state model that accounts for the physical distinction
      between tight inner and loose outer transition states. The predicted rate
      constants, which cover the range from 200 to 2000 K, are found to be in excellent
      agreement with the available experimental data, with a maximum observed
      discrepancy of about 40%. 

PMID- 24093492
TI  - Lipoproteins of slow-growing Mycobacteria carry three fatty acids and are N
      acylated by apolipoprotein N-acyltransferase BCG_2070c.
AB  - BACKGROUND: Lipoproteins are virulence factors of Mycobacterium tuberculosis.
      Bacterial lipoproteins are modified by the consecutive action of
      preprolipoprotein diacylglyceryl transferase (Lgt), prolipoprotein signal
      peptidase (LspA) and apolipoprotein N- acyltransferase (Lnt) leading to the
      formation of mature triacylated lipoproteins. Lnt homologues are found in Gram
      negative and high GC-rich Gram-positive, but not in low GC-rich Gram-positive
      bacteria, although N-acylation is observed. In fast-growing Mycobacterium
      smegmatis, the molecular structure of the lipid modification of lipoproteins was
      resolved recently as a diacylglyceryl residue carrying ester-bound palmitic acid
      and ester-bound tuberculostearic acid and an additional amide-bound palmitic
      acid. RESULTS: We exploit the vaccine strain Mycobacterium bovis BCG as model
      organism to investigate lipoprotein modifications in slow-growing mycobacteria.
      Using Escherichia coli Lnt as a query in BLASTp search, we identified BCG_2070c
      and BCG_2279c as putative lnt genes in M. bovis BCG. Lipoproteins LprF, LpqH,
      LpqL and LppX were expressed in M. bovis BCG and BCG_2070c lnt knock-out mutant
      and lipid modifications were analyzed at molecular level by matrix-assisted laser
      desorption ionization time-of-flight/time-of-flight analysis. Lipoprotein N
      acylation was observed in wildtype but not in BCG_2070c mutants. Lipoprotein N-
      acylation with palmitoyl and tuberculostearyl residues was observed. CONCLUSIONS:
      Lipoproteins are triacylated in slow-growing mycobacteria. BCG_2070c encodes a
      functional Lnt in M. bovis BCG. We identified mycobacteria-specific
      tuberculostearic acid as further substrate for N-acylation in slow-growing
      mycobacteria.

PMID- 24093493
TI  - A price and use comparison of generic versus originator cardiovascular medicines:
      a hospital study in Chongqing, China.
AB  - BACKGROUND: Developed countries use generic competition to contain pharmaceutical
      expenditure. China, as a developing and transitional country, has not yet deemed
      an increase in the use of generic products as important; otherwise, much effort
      has been made to decrease the drug prices. This paper aims to explore dynamically
      the price and use comparison of generic and originator drugs in China, and
      estimate the potential savings of patients from switching originator drugs to
      generics. METHODS: A typical hospital in Chongqing, China, was selected to
      examine the price and use comparisons of 12 cardiovascular drugs from 2006 to
      2011. RESULTS: The market share of the 12 generic medicines studied in this paper
      was 34.37% for volume and 31.33% for value in the second half of 2011. The price
      ratio of generic to originator drugs was between 0.34 and 0.98, and the volume
      price index of originators to generics was 1.63. The potential savings of
      patients from switching originator drugs to generics is 65%. CONCLUSION: The
      market share of the generics was lowering and the weighted mean price kept
      increasing in face of the strict price control. Under the background of hospitals
      both prescribing and dispensing medicines, China's comprehensive healthcare
      policy makers should take measures from supply and demand sides to promote the
      consumption of generic medicines.

PMID- 24093494
TI  - A poly(vinyl alcohol)/sodium alginate blend monolith with nanoscale porous
      structure.
AB  - A stimuli-responsive poly(vinyl alcohol) (PVA)/sodium alginate (SA) blend
      monolith with nanoscale porous (mesoporous) structure is successfully fabricated
      by thermally impacted non-solvent induced phase separation (TINIPS) method. The
      PVA/SA blend monolith with different SA contents is conveniently fabricated in an
      aqueous methanol without any templates. The solvent suitable for the fabrication
      of the present blend monolith by TINIPS is different with that of the PVA
      monolith. The nanostructural control of the blend monolith is readily achieved by
      optimizing the fabrication conditions. Brunauer Emmett Teller measurement shows
      that the obtained blend monolith has a large surface area. Pore size distribution
      plot for the blend monolith obtained by the non-local density functional theory
      method reveals the existence of the nanoscale porous structure. Fourier transform
      infrared analysis reveals the strong interactions between PVA and SA. The pH
      responsive property of the blend monolith is investigated on the basis of
      swelling ratio in different pH solutions. The present blend monolith of
      biocompatible and biodegradable PVA and SA with nanoscale porous structure has
      large potential for applications in biomedical and environmental fields. 

PMID- 24093495
TI  - The increasing application of multiplex nucleic acid detection tests to the
      diagnosis of syndromic infections.
AB  - On 14 January 2013, the US Food and Drug Administration (FDA) announced
      permission for a multiplex nucleic acid test, the xTAG(r) Gastrointestinal
      Pathogen Panel (GPP) (Luminex Corporation, USA), which simultaneously detects 11
      common viral, bacterial and parasitic causes of infectious gastroenteritis, to be
      marketed in the USA. This announcement reflects the current move towards the
      development and commercialization of detection technologies based on nucleic acid
      amplification techniques for diagnosis of syndromic infections. We discuss the
      limitations and advantages of nucleic acid amplification techniques and the
      recent advances in Conformite Europeene - in-vitro diagnostic (CE-IVD)-approved
      multiplex real-time PCR kits for the simultaneous detection of multiple targets
      within the clinical diagnostics market.

PMID- 24093496
TI  - Hydrogen sulfide is an endogenous regulator of aging in Caenorhabditis elegans.
AB  - AIMS: To investigate the role of endogenous hydrogen sulfide (H2S) in the control
      of aging and healthspan of Caenorhabditis elegans. RESULTS: We show that the
      model organism, C. elegans, synthesizes H2S. Three H2S-synthesizing enzymes are
      present in C. elegans, namely cystathionine gamma lyase (CSE), cystathionine beta
      synthetase, and 3-mercaptopyruvate transferase (MPST or 3-MST). Genetic
      deficiency of mpst-1 (3-MST orthologue 1), but not cth-2 (CSE orthologue),
      reduced the lifespan of C. elegans. This effect was reversed by a pharmacological
      H2S donor (GYY4137). GYY4137 also reduced detrimental age-dependent changes in a
      range of physiological indices, including pharyngeal contraction and defecation.
      Treatment of C. elegans with GYY4137 increased the expression of several age
      related, stress response, and antioxidant genes, whereas MitoSOX Red
      fluorescence, indicative of reactive oxygen species generation, was increased in
      mpst-1 knockouts and decreased by GYY4137 treatment. GYY4137 additionally
      increased the lifespan in short-lived mev-1 mutants with elevated oxidative
      stress and protected wild-type C. elegans against paraquat poisoning. The
      lifespan-prolonging and health-promoting effects of H2S in C. elegans are likely
      due to the antioxidant action of this highly cell-permeable gas. INNOVATION: The
      possibility that novel pharmacological agents based on the principle of H2S
      donation may be able to retard the onset of age-related disease by slowing the
      aging process warrants further study. CONCLUSION: Our results show that H2S is an
      endogenous regulator of oxidative damage, metabolism, and aging in C. elegans and
      provide new insight into the mechanisms, which control aging in this model
      organism.

PMID- 24093497
TI  - Cell trivision of hyperploid cells.
AB  - Malignant transformation is likely to render cells hyperploid, primarily
      tetraploid. We have measured the frequency of division into three rather than two
      daughter cells as a function of ploidy. Such trivisions were followed in near
      tetraploid uveal melanoma (UM), hypotetraploid HaCaT (<4 N), hypertriploid HeLa
      (>3 N), and in near-diploid (~2 N) lung epithelial cell lines by time-lapse image
      analyses. A stepwise analysis of cytokinesis revealed higher frequency of cell
      trivisions relative to divisions in hyperploid HeLa (1:24, 4%), HaCaT (1:126,
      8%), and UM (1:186, 0.5%) cells. The occurrence of trivision was significantly
      lower in near-diploid endothelial cells (1:1400, 0.07%). We have previously
      observed the phenomenon of trivision in HaCaT cells treated with heavy metal
      lead, and here we describe that trivision is a spontaneous process taking place
      without genotoxic treatment. Beside re-diploidization by trivision, the
      hyperploid state decreases the cell size of the daughter cells and is likely to
      increase the time of cytokinesis. On the basis of the results, it is hypothesized
      that among other cancer-related causes, hyperploidy could be related to cell
      trivision, could cause random aneuploidy, and could generate new cancer-specific
      karyotypes. 

PMID- 24093498
TI  - Incidence, risk factors and prediction of post-operative acute kidney injury
      following cardiac surgery for active infective endocarditis: an observational
      study.
AB  - INTRODUCTION: Cardiac surgery is frequently needed in patients with infective
      endocarditis (IE). Acute kidney injury (AKI) often complicates IE and is
      associated with poor outcomes. The purpose of the study was to determine the risk
      factors for post-operative AKI in patients operated on for IE. METHODS: A
      retrospective, non-interventional study of prospectively collected data (2000
      2010) included patients with IE and cardiac surgery with cardio-pulmonary bypass.
      The primary outcome was post-operative AKI, defined as the development of AKI or
      progression of AKI based on the acute kidney injury network (AKIN) definition. We
      used ensemble machine learning ("Super Learning") to develop a predictor of AKI
      based on potential risk factors, and evaluated its performance using V-fold cross
      validation. We identified clinically important predictors among a set of risk
      factors using Targeted Maximum Likelihood Estimation. RESULTS: 202 patients were
      included, of which 120 (59%) experienced a post-operative AKI. 65 (32.2%)
      patients presented an AKI before surgery while 91 (45%) presented a progression
      of AKI in the post-operative period. 20 patients (9.9%) required a renal
      replacement therapy during the post-operative ICU stay and 30 (14.8%) died during
      their hospital stay. The following variables were found to be significantly
      associated with renal function impairment, after adjustment for other risk
      factors: multiple surgery (OR: 4.16, 95% CI: 2.98-5.80, p<0.001), pre-operative
      anemia (OR: 1.89, 95% CI: 1.34-2.66, p<0.001), transfusion requirement during
      surgery (OR: 2.38, 95% CI: 1.55-3.63, p<0.001), and the use of vancomycin (OR:
      2.63, 95% CI: 2.07-3.34, p<0.001), aminoglycosides (OR: 1.44, 95% CI: 1.13-1.83,
      p=0.004) or contrast iodine (OR: 1.70, 95% CI: 1.37-2.12, p<0.001). Post
      operative but not pre-operative AKI was associated with hospital mortality.
      CONCLUSIONS: Post-operative AKI following cardiopulmonary bypass for IE results
      from additive hits to the kidney. We identified several potentially modifiable
      risk factors such as treatment with vancomycin or aminoglycosides or pre
      operative anemia.

PMID- 24093499
TI  - Bazedoxifene + conjugated estrogens in HT for the prevention of osteoporosis and
      treatment of vasomotor symptoms associated with the menopause.
AB  - INTRODUCTION: The recent concept that estrogen agonist-antagonists, often
      referred to as selective estrogen receptor modulators, can be combined with an
      estrogen has led to the development of a novel form of menopausal therapy called
      Tissue-Selective Estrogen Complex (TSEC). This paper reviews the TSEC
      bazedoxifene and conjugated equine estrogens (BZA/CE). AREAS COVERED: This review
      is based on clinical trials and a PubMed search. The pharmacokinetics and
      pharmacodynamics of BZA in BZA plus CE are reviewed. This review outlines the
      effects of this particular TSEC, which maintains or increases bone mineral
      density in women at high risk for osteoporosis, and has clinical qualities of a
      promising new menopausal therapy. The potential adverse effects of BZA/CE
      combinations are summarized. EXPERT OPINION: A TSEC that contains CE and BZA that
      has both estrogen agonist and antagonist effects has reached clinical
      development. Phase III clinical trials show this TSEC relieves hot flashes,
      improves vulvo-vaginal atrophy and its symptoms, does not stimulate the
      endometrium, and prevents bone loss. In the trials so far it appears to have a
      good safety and tolerability profile. The optimum combination of BZA/CE
      combination is 20 mg BZA with CE 0.45 and 0.625 mg daily.

PMID- 24093501
TI  - Plasmon-induced hot electron transfer from the Au tip to CdS rod in CdS-Au
      nanoheterostructures.
AB  - The plasmon-exciton interaction mechanisms in CdS-Au colloidal quantum-confined
      plexcitonic nanorod heterostructures have been studied by transient absorption
      spectroscopy. Optical excitation of plasmons in the Au tip leads to hot electron
      injection into the CdS rod with a quantum yield of ~2.75%. This finding suggests
      the possibility of further optimization of plasmon-induced hot electron injection
      efficiency through controlling the size and shape of the plasmonic and excitonic
      domains for potential light harvesting applications.

PMID- 24093502
TI  - Exploration of risk taking behaviors and perceived susceptibility of colorectal
      cancer among Malaysian adults: a community based cross-sectional study.
AB  - BACKGROUND: Perceived susceptibility to an illness has been shown to affect
      Health-risk behavior. The objective of the present study was to determine the
      risk taking behaviors and the demographic predictors of perceived susceptibility
      to colorectal cancer in a population-based sample. METHODS: A cross-sectional
      study was carried out among 305 Malaysian adults in six major districts, selected
      from urban, semi-urban, and rural settings in one state in Malaysia. A self
      administered questionnaire was used in this study. It was comprised of socio
      demographics, risk-taking behaviors, and validated domains of the Health Belief
      Model (HBM). RESULTS: The mean (+/- SD) age of the respondents was 34.5 (+/- 9.6)
      and the majority (59.0%) of them were 30 years or older. Almost 20.7% of the
      respondents felt they were susceptible to colorectal cancer. Self-reported
      perceived susceptibility mirrored unsatisfactory screening behaviors owing to the
      lack of doctors' recommendation, ignorance of screening modalities,
      procrastination, and the perception that screening was unnecessary. Factors
      significantly associated with perceived susceptibility to colorectal cancer were
      gender (OR = 1.8, 95% CI 1.0-3.3), age (OR = 2. 2, 95% CI 1.2-4.0), ethnicity (OR
      = 0. 3, 95% CI 0.2-0.6), family history of colorectal cancer (OR = 3. 2, 95% CI
      1.4-7.4) and alcohol intake (OR = 3.9, 95% CI 2.1-7.5). CONCLUSION: The present
      study revealed that screening behavior among respondents was unsatisfactory.
      Hence, awareness of the importance of screening to prevent colorectal cancers is
      imperative.

PMID- 24093503
TI  - Palladium(II)-catalyzed ortho-arylation of benzylic phosphonic monoesters using
      potassium aryltrifluoroborates.
AB  - The new monophosphonic acid directing group was successfully utilized in the Pd
      (II)-catalyzed ortho-arylation of benzylic phosphonic monoesters using potassium
      aryltrifluoroborates. A wide range of benzylic phosphonic monoesters underwent
      clean ortho-arylation in high yields, and excellent functional group tolerance
      was also observed. 

PMID- 24093504
TI  - A repeat-dose thorough QT study of inhaled fluticasone furoate/vilanterol
      combination in healthy subjects.
AB  - AIMS: This study was designed as a thorough QT (TQT) study to evaluate the
      effects of fluticasone furoate (FF)/vilanterol (VI) in healthy subjects.
      Supportive data from a TQT study conducted with FF are also presented. METHODS:
      This was a randomized, placebo- and positive-controlled, double-dummy, double
      blind, four-way crossover study, in which healthy subjects (n = 85) were
      randomized to 7 days of once-daily treatment of FF/VI (200/25 or 800/100 MUg) or
      placebo or single-dose oral moxifloxacin (single-blind, 400 mg). In the
      supportive TQT study, subjects (n = 40) were randomized to single-dose inhaled FF
      (4000 MUg), oral moxifloxacin (400 mg) or placebo. RESULTS: There was a lack of
      effect of FF/VI (200/25 MUg) on QTcF (Fridericia's correction); all time-matched
      mean differences from baseline relative to placebo (0-24 h) were <5 ms, with
      upper 90% confidence intervals (CI) of <10 ms. At 800/100 MUg, FF/VI had no
      significant clinical effect on QTcF except at 30 min postdose when the 90% CI was
      >10 ms [mean (90% CI), 9.6 ms (7.2, 12.0)]. No effect on QTci (individually
      corrected) was observed at either strength of FF/VI, with mean time-matched
      treatment differences <5 ms at all time points [upper 90% CIs <10 ms (0-24 h)].
      Assay sensitivity was confirmed; moxifloxacin prolonged QTcF and QTci, with time
      matched mean differences from baseline relative to placebo of >10 ms (1-8 h
      postdose). CONCLUSIONS: Repeat once-daily dosing of FF/VI (200/25 MUg), which is
      the highest therapeutic strength used in phase III studies, is not associated
      with QTc prolongation in healthy subjects. Supratherapeutic strength FF/VI
      (800/100 MUg) demonstrated a small transient effect on QTcF but not on QTci.

PMID- 24093507
TI  - Two trisomy 22 live births in one hospital in 15 months: is it as rare as we
      thought?
AB  - We report two cases of complete non-mosaic trisomy 22 who were born within 15
      months of each other in KwaZulu Natal, South Africa. In an effort to consolidate
      diagnostic criteria to suspect trisomy 22 prior to chromosomal testing, we
      compare the clinical features of these infants with those of 23 other trisomy 22
      live borns presented in the literature. We further compare the clinical phenotype
      of trisomy 22 with those of trisomies 13 and 18 to delineate a clinical picture
      to presume possible trisomy 22 soon after birth. Dysmorphic features which
      distinguish trisomy 22 from trisomy 13 and 18 include hypertelorism, long
      philtrum, long and thin upper lip, webbing of the neck, low set, wide spread
      nipples and an abnormal anus. Given the poor prognosis of this disorder and early
      mortality of most confirmed cases, non-aggressive versus aggressive treatment
      measures should be weighed up as soon after birth as possible. 

PMID- 24093505
TI  - HINT1 protein cooperates with cannabinoid 1 receptor to negatively regulate
      glutamate NMDA receptor activity.
AB  - BACKGROUND: G protein-coupled receptors (GPCRs) are the targets of a large number
      of drugs currently in therapeutic use. Likewise, the glutamate ionotropic N
      methyl-D-aspartate receptor (NMDAR) has been implicated in certain neurological
      disorders, such as neurodegeration, neuropathic pain and mood disorders, as well
      as psychosis and schizophrenia. Thus, there is now an important need to
      characterize the interactions between GPCRs and NMDARs. Indeed, these
      interactions can produce distinct effects, and whereas the activation of Mu
      opioid receptor (MOR) increases the calcium fluxes associated to NMDARs, that of
      type 1 cannabinoid receptor (CNR1) antagonizes their permeation. Notably, a
      series of proteins interact with these receptors affecting their responses and
      interactions, and then emerge as novel therapeutic targets for the aforementioned
      pathologies. RESULTS: We found that in the presence of GPCRs, the HINT1 protein
      influences the activity of NMDARs, whereby NMDAR activation was enhanced in
      CNR1+/+/HINT1-/- cortical neurons and the cannabinoid agonist WIN55,212-2
      provided these cells with no protection against a NMDA insult. NMDAR activity was
      normalized in these cells by the lentiviral expression of HINT1, which also
      restored the neuroprotection mediated by cannabinoids. NMDAR activity was also
      enhanced in CNR1-/-/HINT1+/+ neurons, although this activity was dampened by the
      expression of GPCRs like the MOR, CNR1 or serotonin 1A (5HT1AR). CONCLUSIONS: The
      HINT1 protein plays an essential role in the GPCR-NMDAR connection. In the
      absence of receptor activation, GPCRs collaborate with HINT1 proteins to
      negatively control NMDAR activity. When activated, most GPCRs release the control
      of HINT1 and NMDAR responsiveness is enhanced. However, cannabinoids that act
      through CNR1 maintain the negative control of HINT1 on NMDAR function and their
      protection against glutamate excitotoxic insult persists.

PMID- 24093506
TI  - The effects of augmented visual feedback during balance training in Parkinson's
      disease: study design of a randomized clinical trial.
AB  - BACKGROUND: Patients with Parkinson's disease often suffer from reduced mobility
      due to impaired postural control. Balance exercises form an integral part of
      rehabilitative therapy but the effectiveness of existing interventions is
      limited. Recent technological advances allow for providing enhanced visual
      feedback in the context of computer games, which provide an attractive
      alternative to conventional therapy. The objective of this randomized clinical
      trial is to investigate whether a training program capitalizing on virtual
      reality-based visual feedback is more effective than an equally-dosed
      conventional training in improving standing balance performance in patients with
      Parkinson's disease. METHODS/DESIGN: Patients with idiopathic Parkinson's disease
      will participate in a five-week balance training program comprising ten treatment
      sessions of 60 minutes each. Participants will be randomly allocated to (1) an
      experimental group that will receive balance training using augmented visual
      feedback, or (2) a control group that will receive balance training in accordance
      with current physical therapy guidelines for Parkinson's disease patients.
      Training sessions consist of task-specific exercises that are organized as a
      series of workstations. Assessments will take place before training, at six
      weeks, and at twelve weeks follow-up. The functional reach test will serve as the
      primary outcome measure supplemented by comprehensive assessments of functional
      balance, posturography, and electroencephalography. DISCUSSION: We hypothesize
      that balance training based on visual feedback will show greater improvements on
      standing balance performance than conventional balance training. In addition, we
      expect that learning new control strategies will be visible in the co-registered
      posturographic recordings but also through changes in functional connectivity.

PMID- 24093508
TI  - Dual functionalization of poly(epsilon-caprolactone) film surface through
      supramolecular assembly with the aim of promoting in situ endothelial progenitor
      cell attachment on vascular grafts.
AB  - In this study, we developed a method for the dual functionalization of a
      poly(epsilon-caprolactone) (PCL) surface by means of the supramolecular assembly
      technology. Polyethylene glycol (PEG), with resistance to protein adsorption, and
      TPSLEQRTVYAK (TPS) peptide, which can specifically bind endothelial progenitor
      cells (EPCs), were immobilized on the PCL surface through host-guest inclusion
      complexation. The chemical composition as well as the hydrophilic/hydrophobic
      property of the functionalized surface was characterized by X-ray photoelectron
      spectroscopy and water contact angle measurements. The relative composition of
      two functional molecules on the dually functionalized surface was further
      analyzed by fluorescence quantification. Finally, the fibrinogen adsorption,
      platelet adhesion and activation, and selective attachment of cells were
      systematically evaluated on the functionalized surface. The results show that the
      presence of PEG evidently inhibited the adsorption of plasma protein and platelet
      adhesion, thus reducing the possibility of thrombus formation on the
      functionalized surface. At the same time, the TPS-functionalized surface
      demonstrated enhanced attachment toward EPC compared with the surfaces in the
      absence of TPS functionalization. For the surface functionalized by both PEG and
      TPS, the functions provided by each component have been well demonstrated. The
      relative composition of the PEG and TPS could be further fine-tuned by adjusting
      the feeding ratio. All these results indicate that the dually functionalized
      surface developed in this study is a suitable candidate for vascular graft to
      induce and promote in situ endothelialization. 

PMID- 24093509
TI  - Preeclampsia is an independent risk factor for spontaneous intestinal perforation
      in very preterm infants.
AB  - BACKGROUND: Spontaneous intestinal perforation (SIP) is an important surgical
      emergency in preterm infants. AIMS: To evaluate the effect of maternal
      preeclampsia on development of SIP in premature infants. STUDY DESIGN:
      Retrospective observational study in a large tertiary neonatal intensive care
      unit. SUBJECTS: The preterm infants of <=32 weeks of gestational age and
      birthweight <=1500 g who were hospitalized were enrolled. OUTCOME MEASURES: The
      primary outcome was to determine the association between preeclampsia and SIP.
      RESULTS: A total of 22 infants had SIP diagnosis. The incidence of SIP in infants
      born to preeclamptic mothers (6.2%) was significantly higher compared with those
      born to normotensive mothers (0.2%). In multinominal logistic regression model,
      preeclampsia was found to be an independent risk factor of SIP with an odds ratio
      of 13.5 (95% confidence interval 2.82-65.1). CONCLUSIONS: Maternal preeclampsia
      seemed to be an independent risk factor for development of SIP in premature
      infants.

PMID- 24093511
TI  - Accurate analytic potential and Born-Oppenheimer breakdown functions for MgH and
      MgD from a direct-potential-fit data analysis.
AB  - New high-resolution visible Fourier transform emission spectra of the A (2)Pi ->
      X (2)Sigma(+) and B' (2)Sigma(+) -> X (2)Sigma(+) systems of (24)MgD and of the
      B' (2)Sigma(+) -> X (2)Sigma(+) systems of (25,26)MgD and (25,26)MgH have been
      combined with earlier results for (24)MgH in a multi-isotopologue direct
      potential-fit analysis to yield improved analytic potential energy and Born
      Oppenheimer breakdown functions for the ground X (2)Sigma(+) state of MgH.
      Vibrational levels of the ground state of (24)MgD were observed up to v" = 15,
      which is bound by only 30.6 +/- 0.10 cm(-1). Including deuteride and minor
      magnesium isotopologue data allowed us also to determine the adiabatic Born
      Oppenheimer breakdown effects in this molecule. The fitting procedure used the
      recently developed Morse/Long-Range (MLR) potential energy function, whose
      asymptotic behavior incorporates the correct inverse-power form. A spin-splitting
      radial correction function to take account of the (2)Sigma spin-rotation
      interaction was also determined. Our refined value for the ground-state
      dissociation energy of the dominant isotopologue ((24)MgH) is D(e) = 11,104.25 +/
      0.8 cm (-1), in which the uncertainty also accounts for the model dependence of
      the fitted D(e) values for a range of physically acceptable fits. We were also
      able to determine the marked difference in the well depths of (24)MgH and (24)MgD
      (with the deuteride potential curve being 7.58 +/- 0.30 cm(-1) deeper than that
      of the hydride) as well as smaller well-depth differences for the minor (25,26)Mg
      isotopologues. This analytic potential function also predicts that the highest
      bound level of (24)MgD is v" = 16 and that it is bound by only 2.73 +/- 0.10 cm(
      1).

PMID- 24093510
TI  - Transposable elements and their potential role in complex lung disorder.
AB  - Transposable elements (TEs) are a class of mobile genetic elements (MGEs) that
      were long regarded as junk DNA, which make up approximately 45% of the genome.
      Although most of these elements are rendered inactive by mutations and other gene
      silencing mechanisms, TEs such as long interspersed nuclear elements (LINEs) are
      still active and translocate within the genome. During transposition, they may
      create lesions in the genome, thereby acting as epigenetic modifiers.
      Approximately 65 disease-causing LINE insertion events have been reported thus
      far; however, any possible role of TEs in complex disorders is not well
      established. Chronic obstructive pulmonary disease (COPD) is one such complex
      disease that is primarily caused by cigarette smoking. Although the exact
      molecular mechanism underlying COPD remains unclear, oxidative stress is thought
      to be the main factor in the pathogenesis of COPD. In this review, we explore the
      potential role of oxidative stress in epigenetic activation of TEs such as LINEs
      and the subsequent cascade of molecular damage. Recent advancements in sequencing
      and computation have eased the identification of mobile elements. Therefore, a
      comparative study on the activity of these elements and markers for genome
      instability would give more insight on the relationship between MGEs and complex
      disorder such as COPD. 

PMID- 24093512
TI  - Excitotoxic neuronal cell death during an oligodendrocyte-directed CD8+ T cell
      attack in the CNS gray matter.
AB  - BACKGROUND: Neural-antigen reactive cytotoxic CD8+ T cells contribute to neuronal
      dysfunction and degeneration in a variety of inflammatory CNS disorders. Facing
      excess numbers of target cells, CNS-invading CD8+ T cells cause neuronal cell
      death either via confined release of cytotoxic effector molecules towards
      neurons, or via spillover of cytotoxic effector molecules from 'leaky'
      immunological synapses and non-confined release by CD8+ T cells themselves during
      serial and simultaneous killing of oligodendrocytes or astrocytes. METHODS: Wild
      type and T cell receptor transgenic CD8+ T cells were stimulated in vitro, their
      activation status was assessed by flow cytometry, and supernatant glutamate
      levels were determined using an enzymatic assay. Expression regulation of
      molecules involved in vesicular glutamate release was examined by quantitative
      real-time PCR, and mechanisms of non-vesicular glutamate release were studied by
      pharmacological blocking experiments. The impact of CD8+ T cell-mediated
      glutamate liberation on neuronal viability was studied in acute brain slice
      preparations. RESULTS: Following T cell receptor stimulation, CD8+ T cells
      acquire the molecular repertoire for vesicular glutamate release: (i) they
      upregulate expression of glutaminase required to generate glutamate via
      deamination of glutamine and (ii) they upregulate expression of vesicular proton
      ATPase and vesicular glutamate transporters required for filling of vesicles with
      glutamate. Subsequently, CD8+ T cells release glutamate in a strictly stimulus
      dependent manner. Upon repetitive T cell receptor stimulation, CD25high CD8+ T
      effector cells exhibit higher estimated single cell glutamate release rates than
      CD25low CD8+ T memory cells. Moreover, glutamate liberation by oligodendrocyte
      reactive CD25high CD8+ T effector cells is capable of eliciting collateral
      excitotoxic cell death of neurons (despite glutamate re-uptake by glia cells and
      neurons) in intact CNS gray matter. CONCLUSION: Glutamate release may represent a
      crucial effector pathway of neural-antigen reactive CD8+ T cells, contributing to
      excitotoxicity in CNS inflammation.

PMID- 24093513
TI  - Augmented cytotoxicity of hydroxycamptothecin-loaded nanoparticles in lung and
      colon cancer cells by chemosensitizing pharmaceutical excipients.
AB  - The aim of this was to investigate and compare the chemosensitizing effect of
      some pharmaceutical excipients (TPGS, Pluronic P85 and chitosan) by evaluating
      the cytotoxicity of the chemotherapeutic drug Hydroxy Camptothecin (HCPT) loaded
      into PLGA nanoparticles. Different nanoparticles formulations were developed and
      evaluated for size, zeta potential, morphology, loading and encapsulation
      efficiency as well as in vitro drug release. The cytotoxicity of the
      nanoparticles was evaluated by MTT assay in A549 (human lung carcinoma cell line)
      and HT29 (human colon carcinoma cell line) whereas their cellular uptake was
      determined by confocal laser scanning microscopy and microfluorimetry assay. The
      results revealed that nanoparticles possessed a desirable nanometric size
      (revealed by dynamic light scattering measurements and TEM) with appreciable HCPT
      encapsulation (>48%) and negative surface charge that was switched to positive
      upon coating with chitosan. The nanoparticles adopted a sustained release phase
      preceded by initial burst of HCPT that was reduced by chitosan coating. The
      cytotoxicity of the nanoparticles in A549 and HT29 cells was significantly
      augmented compared to simple drug solution and basic nanoparticles without
      excipients. The excipients could be ranked according to their IC50 lowering
      effect in the following order [TPGS (sixfold lower IC50) > Pluronic P85 >
      Chitosan]. The augmented cytotoxicity and chemosensitizing effect might be
      attributed to overcoming drug efflux (in case of TPGS 1000 or Pluronic P85)
      and/or maximizing internalization by cancer cells (chitosan coating). Acting as
      chemopotentiators, the studied excipients could have potential in reducing
      therapeutic HCPT doses and minimizing adverse effects in lung and colon
      chemotherapy.

PMID- 24093514
TI  - New insights into drug development for pediatric solid tumors: what preclinical
      data justify clinical trials in pediatric cancer?

PMID- 24093516
TI  - Trends in quality of care among patients with incident heart failure in Denmark
      2003-2010: a nationwide cohort study.
AB  - BACKGROUND: The treatment of heart failure (HF) is complex and the prognosis
      remains serious. A range of strategies is used across health care systems to
      improve the quality of care for HF patients. We present results from a nationwide
      multidisciplinary initiative to monitor and improve the quality of care and
      clinical outcome of HF patients using indicator monitoring combined with
      systematic auditing. METHODS: We conducted a nationwide, population-based
      prospective study using data from the Danish Heart Failure Registry. The registry
      systematically monitors and audits the use of guideline recommended processes of
      care at Danish hospital departments treating incident HF patients. We identified
      patients registered between 2003 and 2010 (n = 24,504) and examined changes in
      use of recommended processes of care and 1-year mortality. RESULTS: The use of
      the majority of the recommended processes of care increased substantially from
      2003 to 2010: echocardiography (from 62.7% to 90.5%; Relative Risk (RR) 1.45 (95%
      CI, 1.39-1.50)), New York Heart Association classification (from 29.4% to 85.5%;
      RR 2.91 (95% CI, 2.69-3.14)), betablockers (from 72.6% to 88.3%; RR 1.23 (95% CI,
      1.15-1.29)), physical training (from 5.6% to 22.8%; RR 4.04 (95% CI, 2.96-4.52)),
      and patient education (from 49.3% to 81.4%; RR 1.65 (95% CI, 1.52-1.80)). Use of
      ACE/ATII inhibitors remained stable (from 92.0% to 93.2%; RR 1.01 (95% CI, 0.99
      1.04)). During the same period, 1-year mortality dropped from 20.5% to 12.8%
      (adjusted Hazard Ratio 0.79 (95% CI, 0.65-0.96). CONCLUSIONS: Use of guideline
      recommended processes of care has improved among patients with incident HF
      included in the Danish Heart Failure Registry between 2003 and 2010. During the
      same period, a decrease in mortality was observed.

PMID- 24093517
TI  - Enhanced surveillance for toxoplasmosis in England and Wales, 2008-2012.
AB  - A report on Toxoplasma gondii by the UK Advisory Committee on the Microbiological
      Safety of Food recommended that more accurate figures on the burden of disease in
      the UK are needed. We present the first 5 years of data from an enhanced
      surveillance scheme for toxoplasmosis in England and Wales. Between 2008 and
      2012, 1824 cases were reported, with an average of 365 each year. There were 1109
      immunocompetent cases, the majority presenting with lymphadenopathy, and 364
      immunosuppressed cases, with central nervous system and systemic symptoms most
      frequently reported. There were also 190 pregnant and 33 congenital cases. Of the
      pregnant cases, 148 were asymptomatic (probably detected during screening), while
      28 suffered a fetal loss or stillbirth. The enhanced surveillance system has led
      to an improvement in the detection of toxoplasmosis in England and Wales.
      However, numbers are still likely to be an underestimate, biasing towards the
      more severe infections.

PMID- 24093518
TI  - Down-regulation of microglial activity attenuates axotomized nigral dopaminergic
      neuronal cell loss.
AB  - BACKGROUND: There is growing evidence that inflammatory processes of activated
      microglia could play an important role in the progression of nerve cell damage in
      neurodegenerative disorders such as Parkinson's disease and Alzheimer's disease
      which harbor features of chronic microglial activation, though the precise
      mechanism is unknown. In this study, we presented in vivo and ex vivo
      experimental evidences indicating that activated microglia could exacerbate the
      survival of axotomized dopaminergic neurons and that appropriate inactivation of
      microglia could be neuroprotective. RESULTS: The transection of medial forebrain
      bundle (MFB) of a rat induced loss of dopaminergic neurons in a time-dependent
      manner and accompanied with microglial activation. Along with microglial
      activation, production of reactive oxygen species (ROS) was upregulated and
      TH/OX6/hydroethidine triple-immunofluorescence showed that the microglia mainly
      produced ROS. When the activated microglial cells that were isolated from the
      substantia nigra of the MFB axotomized animal, were transplanted into the
      substantia nigra of which MFB had been transected at 7 days ago, the survival
      rate of axotomized dopaminergic neurons was significantly reduced as compared
      with sham control. Meanwhile, when the microglial activation was attenuated by
      administration of tuftsin fragment 1-3 (microglia inhibitory factor) into the
      lateral ventricle using mini-osmotic pump, the survival rate of axotomized
      dopaminergic neurons was increased. CONCLUSION: The present study suggests that
      activated microglia could actively produce and secrete unfavorable toxic
      substances, such as ROS, which could accelerate dopaminergic neuronal cell loss.
      So, well-controlled blockade of microglial activation might be neuroprotective in
      some neuropathological conditions.

PMID- 24093519
TI  - Survey of controversial issues of end-of-life treatment decisions in Korea:
      similarities and discrepancies between healthcare professionals and the general
      public.
AB  - INTRODUCTION: End-of-life (EOL) treatment issues have recently gained societal
      attention after the Korean Supreme Court's ruling that the presumed wishes of an
      elderly woman in a persistent vegetative state (PVS) should be honored. We tried
      to evaluate what Koreans thought about controversial issues regarding EOL
      treatments. METHODS: We surveyed Koreans with the following questions: 1) are
      ventilator-dependent PVS patients candidates for end-of life treatment decisions?
      2) Is withholding and withdrawing EOL treatment the same thing? 3) In an
      unconscious, terminally ill patient, whose wishes are unknown, how should EOL
      decisions be made? 4) How should we settle disagreement amongst medical staff and
      the patient's family on EOL decisions? RESULTS: One thousand Koreans not working
      in healthcare and five hundred healthcare professionals responded to the survey.
      Fifty-seven percent of Koreans not working in healthcare and sixty seven percent
      of Korean healthcare professionals agreed that ventilator-dependent PVS patients
      are candidates for EOL treatment decisions. One quarter of all respondents
      regarded withholding and withdrawing EOL treatment as equal. Over 50% thought
      that EOL treatment decisions should be made through discussions between the
      physician and the patient's family. For conflict resolution, 75% of Koreans not
      working in healthcare preferred direct settlement between the medical staff and
      the patient's family while 55% of healthcare professionals preferred the hospital
      ethics committee. CONCLUSIONS: Unsettled issues in Korea regarding EOL treatment
      decision include whether to include ventilator-dependent PVS patients as
      candidates of EOL treatment decision and how to sort out disagreements regarding
      EOL treatment decisions. Koreans viewed withholding and withdrawing EOL treatment
      issues differently.

PMID- 24093520
TI  - Service utilization of Asians and other racial-ethnic groups: comparisons in a
      state substance abuse treatment system.
AB  - Based on an administrative data base of 410,000 substance abuse treatment clients
      in New York State, Asians are a small minority who differ significantly from
      other racial-ethnic groups on income, primary language, treatment setting,
      substance of abuse, referral source, and discharge status. In particular,
      relative to other race-ethnicity groups such as whites, blacks, and Hispanics,
      significantly greater percentages of Asians are referred from drinking-driving
      programs and completed treatment. However, most of the significant differences
      between Asians and other groups are found among clients with a first admission,
      and tended to attenuate among clients with a second or third admission. 

PMID- 24093521
TI  - Substance misuse prevention as corporate social responsibility.
AB  - All sectors of society should be involved in reducing substance misuse, including
      businesses. However, the business sector is typically involved only to the extent
      that their products compel them to be (e.g., alcohol producers promoting
      responsible alcohol consumption). This article examines why business
      participation has been limited and how embedding prevention within a framework of
      health promotion could increase participation. It reviews both Hungarian and
      international cases, concluding that although corporate social responsibility
      (CSR) offers a framework to approach substance misuse reduction, a different
      perception of the role of the business sector is necessary to make it viable. 

PMID- 24093522
TI  - Relative effects of social self-control, sensation seeking, and impulsivity on
      future cigarette use in a sample of high-risk adolescents.
AB  - We used confirmatory factor analysis to compare convergence/divergence across
      self-report measures of social self-control, sensation seeking, and impulsivity
      in a sample of high-risk adolescents. In addition, we tested baseline social self
      control as a predictor of cigarette use one year later, controlling for baseline
      cigarette use, impulsivity/sensation seeking, and demographic variables. Data
      were collected in 2004-2005 from 821 adolescents (M age = 16.3; SD = 1.36)
      enrolled in 14 continuation high schools in Southern California. Of the baseline
      sample, 566 students participated in a follow-up survey one year later. Results
      indicated that social self-control represents a unique dimension of self-control
      and is a salient predictor of future cigarette use. 

PMID- 24093523
TI  - Changes in the prevalence of alcohol in rap music lyrics 1979-2009.
AB  - This study examines the prevalence and context of alcohol references in rap music
      lyrics from 1979 through 2009. Four hundred nine top-ranked rap music songs
      released were sampled from Billboard magazine rating charts. Songs were analyzed
      using systematic content analysis and were coded for alcohol beverage types and
      brand names, drinking behaviors, drinking contexts, attitudes towards alcohol,
      and consequences of drinking. Trends were analyzed using regression analyses. The
      results of the study reveal significant increases in the presence of alcohol in
      rap songs; a decline in negative attitudes towards alcohol; decreases in
      consequences attributed to alcohol; increases in the association of alcohol with
      glamour and wealth, drugs, and nightclubs; and increases in references to liquor
      and champagne. 

PMID- 24093524
TI  - Direct and indirect symptom severity indicators of alcohol dependence and the
      personality concept of the biosocial model.
AB  - Temperament and character factors are strongly related to the developmental,
      clinical, and treatment aspects of alcohol dependence. This study had the aim of
      revealing the underlying personality structure and individual differences in the
      symptoms of alcohol dependence measured by multiple severity indicators. Patients
      with alcohol dependence exhibited higher levels of novelty seeking and harm
      avoidance, and lower levels of persistence, self-directedness, and
      cooperativeness. Especially novelty seeking was connected with more severe
      alcohol dependence. These characteristics could be useful targets of
      interventions and Temperament and Character Inventory is therefore a useful
      measurement to identify patients with more severe alcohol-related problems. 

PMID- 24093525
TI  - Subtypes of attention deficit-hyperactivity disorder (ADHD) and cannabis use.
AB  - The current study examined the association between subtypes of attention
      deficit/hyperactivity disorder (ADHD) and cannabis use within a sample of 2811
      current users. Data were collected in 2012 from a national U.S. survey of
      cannabis users. A series of logistic regression equations and chi-squares were
      assessed for proportional differences between users. When asked about the ADHD
      symptoms they have experienced when not using cannabis, a higher proportion of
      daily users met symptom criteria for an ADHD diagnoses of the subtypes that
      include hyperactive-impulsive symptoms than the inattentive subtype. For nondaily
      users, the proportions of users meeting symptom criteria did not differ by
      subtype. These results have implications for identifying which individuals with
      ADHD might be more likely to self-medicate using cannabis. Furthermore, these
      findings indirectly support research linking relevant cannabinoid receptors to
      regulatory control. 

PMID- 24093526
TI  - A new survey of methamphetamine users in treatment: who they are, why they like
      "meth," and why they need additional services.
AB  - The quality and quantity of illicit methamphetamine has recently increased due to
      introduction of a new precursor, 1-phenyl-2-propanone (P2P). This paper updates
      the problems associated with methamphetamine use. Methamphetamine-using clients
      (N = 222) entering a Texas program participated in computer-assisted interviews
      in 2010 and 2011 about routes of administration, other drugs used, severity of
      dependence, mental and physical health, perceived risks and benefits of use,
      family history, and abuse and neglect experienced as children and adults. Special
      needs of this population include therapies for trauma, gender-focused counseling,
      safe housing, and prevention messages to discourage use of the drug. 

PMID- 24093527
TI  - Are "Legal Highs" users satisfied? Evidence from online customer comments.
AB  - This article describes the results of a clustering analysis of more than 2,100
      comments posted by online purchasers of "Legal Highs" on five websites in 2012.
      The aim is to investigate the reasons for satisfaction/dissatisfaction on the
      part of legal highs users. Our results show that the reasons for satisfaction
      depend on the price/quality ratio and the real effects of the product (compared
      to illicit drugs). Dissatisfaction seems to stem from the disparity between the
      advertising of the product and its real quality. We conclude that online
      purchasers are certainly illicit drug users who consider legal highs as
      substitution products. 

PMID- 24093528
TI  - Synthesis of functionalized tetracyanocyclopentadienides from tetracyanothiophene
      and sulfones.
AB  - Tetracyanothiophene and tetracyano-1,4-dithiin react with a leaving group
      substituted carbon nucleophile such as ethyl benzenesulfonylacetate to afford
      substituted tetracyanocyclopentadienyl sodium derivatives in moderate to high
      yields through a putative condensation and desulfurization pathway. Subsequent
      functional-group transformation reactions on the Cp anion ring provided various
      C5R(CN)4(-) derivatives. 

PMID- 24093529
TI  - Tuning electron transfer rates through molecular bridges in quantum dot
      sensitized oxides.
AB  - Photoinduced electron transfer processes from semiconductor quantum dots (QDs)
      molecularly bridged to a mesoporous oxide phase are quantitatively surveyed using
      optical pump-terahertz probe spectroscopy. We control electron transfer rates in
      donor-bridge-acceptor systems by tuning the electronic coupling strength through
      the use of n-methylene (SH-[CH2]n-COOH) and n-phenylene (SH-[C6H4](n)-COOH)
      molecular bridges. Our results show that electron transfer occurs as a
      nonresonant quantum tunneling process with characteristic decay rates of beta(n)
      = 0.94 +/- 0.08 and beta(n) = 1.25 per methylene and phenylene group,
      respectively, in quantitative agreement with reported conductance measurements
      through single molecules and self-assembled monolayers. For a given QD donor
      oxide acceptor separation distance, the aromatic n-phenylene based bridges allow
      faster electron transfer processes when compared with n-methylene based ones.
      Implications of these results for QD sensitized solar cell design are discussed.

PMID- 24093530
TI  - Delay in diabetic retinopathy screening increases the rate of detection of
      referable diabetic retinopathy.
AB  - AIMS: To assess whether there is a relationship between delay in retinopathy
      screening after diagnosis of type 2 diabetes and level of retinopathy detected.
      METHODS: Patients were referred from 88 primary care practices to an English
      National Health Service diabetic eye screening programme. Data for screened
      patients were extracted from the primary care databases using semi-automated data
      collection algorithms supplemented by validation processes. The programme uses
      two-field mydriatic digital photographs graded by a quality assured team.
      RESULTS: Data were available for 8183 screened patients with diabetes newly
      diagnosed in 2005, 2006 or 2007. Only 163 with type 1 diabetes were identified
      and were insufficient for analysis. Data were available for 8020 with newly
      diagnosed type 2 diabetes. Of these, 3569 were screened within 6 months, 2361
      between 6 and 11 months, 1058 between 12 and 17 months, 366 between 18 and 23
      months, 428 between 24 and 35 months, and 238 at 3 years or more after diagnosis.
      There were 5416 (67.5%) graded with no retinopathy, 1629 (20.3%) with background
      retinopathy in one eye, 753 (9.4%) with background retinopathy in both eyes and
      222 (2.8%) had referable diabetic retinopathy. There was a significant trend (P =
      0.0004) relating time from diagnosis to screening detecting worsening
      retinopathy. Of those screened within 6 months of diagnosis, 2.3% had referable
      retinopathy and, 3 years or more after diagnosis, 4.2% had referable retinopathy.
      CONCLUSIONS: The rate of detection of referable diabetic retinopathy is elevated
      in those who were not screened promptly after diagnosis of type 2 diabetes.

PMID- 24093531
TI  - Natural course of scoliosis in proximal spinal muscular atrophy type II and IIIa:
      descriptive clinical study with retrospective data collection of 126 patients.
AB  - BACKGROUND: Progressive scoliosis, pelvic obliquity and increasing reduction of
      pulmonary function are among the most significant problems for patients with SMA
      type II and SMA type III once they have lost the ability to walk. The aim of this
      study was to examine and document the development and natural course of scoliosis
      in patients with spinal muscular atrophy type II and IIIa. METHODS: For the
      purposes of a descriptive clinical study, we observed 126 patients, 99 with SMA
      II and 27 with SMA IIIa and the data of scoliosis, pelvic obliquity and relative
      age-dependent inspiratory vital capacity were evaluated. RESULTS: Scoliosis and
      pelvic obliquity were regularly observed already in children under 4 years old in
      the group with SMA II. The severity and progression of both conditions were much
      more pronounced in the SMA II group than in the IIIa group. There was already a
      distinct reduction in relative vital capacity in the group of 4- to 6-year-olds
      with SMA II. CONCLUSIONS: The differences between the two SMA types II and IIIa
      described in this study should be taken into consideration when developing new
      treatments and in management of scoliosis in the childhood years of these
      patients.

PMID- 24093533
TI  - Evaluation of the bitter-masking potential of food proteins for EGCG by a cell
      based human bitter taste receptor assay and binding studies.
AB  - Epigallocatechin gallate (EGCG) has been ascribed to several health benefits, but
      its bitter taste influences the liking of products with high concentrations of
      this compound. beta-Casein, in particular, and several gelatins are known as
      strong binders of EGCG, contrary to beta-lactoglobulin. The current study aimed
      at relating the EGCG-binding characteristics of those proteins and their food
      grade equivalents to their effects on reducing bitter receptor activation by EGCG
      in vitro and their bitter-masking potential in vivo. Also in the bitter receptor
      assay, beta-casein showed the strongest effect, with a maximum reduction of
      hTAS2R39 activation of about 93%. A similar potency was observed for Na
      caseinate. beta-Lactoglobulin had little effect on bitter receptor activation, as
      expected based on its low binding affinity for EGCG. The bitter-masking potential
      of Na-caseinate was confirmed in vivo using a trained sensory panel. beta
      Lactoglobulin also slightly reduced EGCG bitter perception, which could not be
      directly related to its binding capacity. The bitter receptor assay appeared to
      be a valid tool to evaluate in vitro the efficacy of food proteins as complexing
      agents for masking bitterness. 

PMID- 24093535
TI  - A resurrection of 7-MEOTA: a comparison with tacrine.
AB  - Alzheimer's disease (AD) is a progressive neurodegenerative dementia which
      currently represents one of the biggest threats for the human kind. The cure is
      still unknown and various hypotheses (cholinergic, amyloidal, oxidative, vascular
      etc.) are investigated in order to understand the pathophysiology of the disease
      and on this basis find an effective treatment. Tacrine, the first approved drug
      for the AD disease treatment, has been reported to be a multitargeted drug,
      however it was withdrawn from the market particularly due to its hepatotoxicity.
      Its derivative 7-methoxytacrine (7- MEOTA) probably due to the different
      metabolization does not exert this side effect. The aim of our study was to
      compare these two cholinesterase inhibitors from various, mainly cholinergic,
      points of view relevant for a potential AD drug. We found that 7-MEOTA does not
      fall behind its more well-known parent compound - tacrine. Furthermore, we found,
      that 7-MEOTA exerts better properties in most of the tests related to a possible
      AD treatment. Only the pharmacokinetics and a higher acetylcholinesterase and
      butyrylcholinesterase inhibitory potency would slightly give advantages to
      tacrine over 7-MEOTA, but concerning its lower toxicity, better antioxidant
      properties, interaction with muscarinic and nicotinic receptors and "safer"
      metabolization provide strong evidence for reconsider 7-MEOTA and its derivatives
      as candidate molecules for the treatment of AD. 

PMID- 24093534
TI  - Histone deacetylase 2 in the mouse hippocampus: attenuation of age-related
      increase by caloric restriction.
AB  - The aging process in the hippocampus is associated with aberrant epigenetic
      marks, such as DNA methylation and histone tail alterations. Recent evidence
      suggests that caloric restriction (CR) can potentially delay the aging process,
      while upregulation of antioxidants may also have a beneficial effect in this
      respect. We have recently observed that CR attenuates age-related changes in the
      levels of the epigenetic molecules DNA methyltransferase 3a, 5-methylcytidine (5-
      mC) and 5-hydroxymethylcytosine in the mouse hippocampus while overexpression of
      the antioxidant Cu/Zn superoxide dismutase 1 (SOD1) does not. However, the impact
      of aging on the levels of histone-modifying enzymes such as histone deacetylase 2
      (HDAC2) in the hippocampus has not been studied in much detail. Here, we
      investigated immunoreactivity (IR) of HDAC2 in three subregions of the
      hippocampus (dentate gyrus, CA3 and CA1-2) of mice taken from large cohorts of
      aging wild-type and transgenic mice overexpressing normal human SOD1, which were
      kept under normal diet or CR from weaning onwards. Independent from the genotype,
      aging (between 12 and 24 months) increased levels of HDAC2 IR in the hippocampus.
      Moreover, CR prevented this age-related increase, particularly in the CA3 and CA1
      2 subregions, while SOD1 overexpression did not. Quantitative image analyses
      showed that HDAC2 IR correlated positively with 5-mC IR while these markers were
      shown to colocalize in the nucleus of hippocampal cells. Together with recent
      literature reports, these findings suggest that altered levels of epigenetic
      regulatory proteins including HDAC2 regulate age-related changes in the mouse
      hippocampus and that CR may prevent these age-related changes. 

PMID- 24093536
TI  - Joint hypermobility, growing pain and obesity are mutually exclusive as causes of
      musculoskeletal pain in schoolchildren.
AB  - OBJECTIVES: Chronic musculoskeletal pain (MSP) is common in children and can be
      due to several non-inflammatory conditions such as the benign joint hypermobility
      syndrome (BJHS), and growing pains (GP). We evaluated frequency, risk factors and
      causes of MSP in a large cohort of healthy schoolchildren. METHODS: We conducted
      a cross sectional study in a cohort of healthy schoolchildren, aged 8-13 years,
      by collecting information and performing a physical examination. The anamnesis
      was focused on family history for MSP, presence and sites of MSP interfering with
      the regular daily activities during the previous 6 months and presence of GP.
      Physical examination included body mass index, pubertal stage and musculoskeletal
      examination focused on the presence of hypermobility according to the Beighton
      criteria. RESULTS: Two hundred and eighty-nine schoolchildren, 143 females and
      146 males, participated in the study. Chronic MSP occurred in 30.4% of subjects,
      BJHS occurred in 13.2%. GJH was more frequent in symptomatic subjects than in
      asymptomatic ones (p=0.054). Symptomatic subjects were more frequently pre
      pubertal than pubertal (p=0.006). In general, GP, BJHS and obesity (OB) were
      mutually exclusive as causes of MSP as, among 88 symptomatic subjects, 52.3% had
      GP, 40.9% presented BJHS, 4.5% were OB and only two (2.3%) presented both BJHS
      and OB. After puberty, GP persisted in 66.7%, BJHS in 26.7% and in association
      with OB in 6.7%. CONCLUSIONS: Approximately one third of schoolchildren suffer
      from MSP. BJHS, GP and OB are mutually exclusive as causes of MSP in
      schoolchildren. Pubertal stage plays an important role in the physiopathology of
      this condition.

PMID- 24093537
TI  - Highly ordered dielectric mirrors via the self-assembly of dendronized block
      copolymers.
AB  - Dendronized block copolymers were synthesized by ruthenium-mediated ring-opening
      methathesis polymerization of exo-norbornene functionalized dendrimer monomers,
      and their self-assembly to dielectric mirrors was investigated. The rigid-rod
      main-chain conformation of these polymers drastically lowers the energetic
      barrier for reorganization, enabling their rapid self-assembly to long-range,
      highly ordered nanostructures. The high fidelity of these dielectric mirrors is
      attributed to the uniform polymer architecture achieved from the construction of
      discrete dendritic repeat units. These materials exhibit light-reflecting
      properties due to the multilayer architecture, presenting an attractive bottom-up
      approach to efficient dielectric mirrors with narrow band gaps. The wavelength of
      reflectance scales linearly with block-copolymer molecular weight, ranging from
      the ultraviolet, through the visible, to the near-infrared. This allows for the
      modulation of photonic properties through synthetic control of the polymer
      molecular weight. This work represents a significant advancement in closing the
      gap between the precision obtained from top-down and bottom-up approaches. 

PMID- 24093538
TI  - Correspondence between cluster-ion and bulk solution thermodynamic properties: on
      the validity of the cluster-pair-based approximation.
AB  - Since the single-ion thermodynamic properties of bulk solutions are not directly
      accessible from experiments, extrapolations have been devised to estimate them
      from experimental measurements on small-clusters. Extrapolations based on the
      cluster-pair-based approximation (CPA) technique (Tissandier et al. J. Phys.
      Chem. A 1998, 102, 7787-7794) and its variants are currently considered one of
      the most reliable source of single-ion hydration thermodynamic data and have been
      used as a benchmark for the development of molecular and continuum solvation
      models. Despite its importance, the CPA has not been thoroughly tested and recent
      studies have indicated inconsistencies with molecular simulations. The present
      work challenges the key CPA assumptions that the hydration properties of single
      cations and anions in growing clusters rapidly converge to each other following a
      monotonous trend. Using a combination of simulation techniques to study the
      transition between alkali halide ions in small clusters and bulk solution, we
      show that this convergence is rather slow and involves a surprising change in
      trends, which can result in significant errors in the original estimated single
      ion properties. When these cluster-size-dependent effects are taken into account,
      the inconsistencies between molecular models and experimental predictions
      disappear, and the value of the proton hydration enthalpy based on the CPA aligns
      with estimates based on other principles. 

PMID- 24093539
TI  - Assessment of interleukin-6, interleukin-8 and interleukin-18 count in the serum
      of IUGR newborns.
AB  - AIM: Aim of this study was to assess concentrations of interleukin-6 (IL-6),
      interleukin-8 (IL-8) and interleukin-18 (IL-18) in the serum of newborns with
      diagnosed intrauterine growth restriction (IUGR) in comparison to concentrations
      in serum of newborns with weight appropriate for gestational age (AGA).
      MATERIALS: Research was conducted at the Lodz Medical University Clinic of
      Neonatology during 2010-2011. Surveyed group consisted of 50 hypotrophic full
      term infants of single pregnancies (average weight: 2329 +/- 287 g); control
      group, enclosing 50 infants AGA (average weight: 3544 +/- 2161 g). Both groups
      received average Apgar score of 9 points. Concentrations of analysed cytokines
      were marked between 4-6 hours after birth. The enzyme-linked immunosorbent assay
      (ELISA) test was used to determine interleukins concentrations. Study was
      prospective. Statistics on the data were conducted with the Kolmogorov-Smirnov
      test. Significance level: p < 0.05. RESULTS: Concentrations of IL-6 and IL-18
      were elevated in the IUGR group in a statistically significant manner in
      comparison to the control group. CONCLUSIONS: An elevated level of IL-6 and IL-18
      in the IUGR group, comparing to control group, signifies the existence of
      inflammation in the process of developing IUGR, therefore, screening tests
      estimating levels of interleukins as IL-6 and IL-18 might be clinically useful in
      predicting the occurrence of IUGR and help preventing it.

PMID- 24093541
TI  - Human adipose stem cells cell sheet constructs impact epidermal morphogenesis in
      full-thickness excisional wounds.
AB  - Among the wide range of strategies to target skin repair/regeneration, tissue
      engineering (TE) with stem cells at the forefront, remains as the most promising
      route. Cell sheet (CS) engineering is herein proposed, taking advantage of
      particular cell-cell and cell-extracellular matrix (ECM) interactions and
      subsequent cellular milieu, to create 3D TE constructs to promote full-thickness
      skin wound regeneration. Human adipose derived stem cells (hASCs) CS were
      obtained within five days using both thermoresponsive and standard cell culture
      surfaces. hASCs-based constructs were then built by superimposing three CS and
      transplanted into full-thickness excisional mice skin wounds with delayed
      healing. Constructs obtained using thermoresponsive surfaces were more stable
      than the ones from standard cell culture surfaces due to the natural adhesive
      character of the respective CS. Both CS-generating strategies lead to prolonged
      hASCs engraftment, although no transdifferentiation phenomena were observed.
      Moreover, our findings suggest that the transplanted hASCs might be promoting
      neotissue vascularization and extensively influencing epidermal morphogenesis,
      mainly through paracrine actions with the resident cells. The thicker epidermis,
      with a higher degree of maturation characterized by the presence of rete ridges
      like structures, as well as a significant number of hair follicles observed after
      transplantation of the constructs combining the CS obtained from the
      thermoresponsive surfaces, reinforced the assumptions of the influence of the
      transplanted hASCs and the importance of the higher stability of these constructs
      promoted by cohesive cell-cell and cell-ECM interactions. Overall, this study
      confirmed the potential of hASCs CS-based constructs to treat full-thickness
      excisional skin wounds and that their fabrication conditions impact different
      aspects of skin regeneration, such as neovascularisation, but mainly epidermal
      morphogenesis. 

PMID- 24093540
TI  - Preoperative cerebrospinal fluid cytokine levels and the risk of postoperative
      delirium in elderly hip fracture patients.
AB  - BACKGROUND: Aging and neurodegenerative disease predispose to delirium and are
      both associated with increased activity of the innate immune system resulting in
      an imbalance between pro- and anti-inflammatory mediators in the brain. We
      examined whether hip fracture patients who develop postoperative delirium have
      altered levels of inflammatory mediators in cerebrospinal fluid (CSF) prior to
      surgery. METHODS: Patients were 75 years and older and admitted for surgical
      repair of an acute hip fracture. CSF samples were collected preoperatively. In an
      exploratory study, we measured 42 cytokines and chemokines by multiplex analysis.
      We compared CSF levels between patients with and without postoperative delirium
      and examined the association between CSF cytokine levels and delirium severity.
      Delirium was diagnosed with the Confusion Assessment Method; severity of delirium
      was measured with the Delirium Rating Scale Revised-98. Mann-Whitney U tests or
      Student t-tests were used for between-group comparisons and the Spearman
      correlation coefficient was used for correlation analyses. RESULTS: Sixty-one
      patients were included, of whom 23 patients (37.7%) developed postsurgical
      delirium. Concentrations of Fms-like tyrosine kinase-3 (P=0.021), Interleukin-1
      receptor antagonist (P=0.032) and Interleukin-6 (P=0.005) were significantly
      lower in patients who developed delirium postoperatively. CONCLUSIONS: Our
      findings fit the hypothesis that delirium after surgery results from a
      dysfunctional neuroinflammatory response: stressing the role of reduced levels of
      anti-inflammatory mediators in this process. TRIAL REGISTRATION: The Effect of
      Taurine on Morbidity and Mortality in the Elderly Hip Fracture Patient.
      REGISTRATION NUMBER: NCT00497978. Local ethical protocol number: NL16222.094.07.

PMID- 24093542
TI  - Compliance to fingolimod and other disease modifying treatments in multiple
      sclerosis patients, a retrospective cohort study.
AB  - BACKGROUND: Adherence to disease-modifying therapies (DMTs) results in the
      reduction of the number and severity of relapses and delays the progression of
      multiple sclerosis (MS). Patients with lower adherence rates experience more
      inpatient visits and higher MS-related medical costs. Fingolimod, the first oral
      DMT approved by the US Food and Drug Administration, may improve the access and
      compliance to MS treatment when compared to injectable DMTs. METHODS: This
      retrospective cohort study used pharmacy claims from Medco Health Solutions,
      Inc., of patients who initiated DMTs between October 2010 and February 2011.
      Initiation was defined as no prescription fills for the same DMT in the prior 12
      months. Patients without a DMT prescription fill 12 months before the index date
      were considered naive users. Compliance was measured via proportion of days
      covered (PDC) and medication possession ratio (MPR) for 12 months post-index.
      Discontinuation was defined as a >=60-day gap of index DMT supply. Cox
      proportional hazard models compared time to discontinuation between cohorts.
      RESULTS: Of 1,891 MS patients (mean age: 45.7; female: 76.4%), 13.1% initiated
      fingolimod, 10.7% interferon beta-1b, 20.0% intramuscular interferon beta-1a,
      18.8% subcutaneous interferon beta-1a, and 37.4% glatiramer acetate. Patients
      initiating fingolimod had highest average PDC and MPR in both experienced
      (fingolimod: mean PDC=0.83, 73.7% with PDC>=0.8; mean MPR=0.92, 90.5% with
      MPR>=0.8) and naive DMT users (fingolimod: mean PDC=0.80, 66.7% with PDC>=0.8;
      mean MPR=0.90, 87.4% with MPR>=0.8). The proportion of patients discontinuing
      index DMT within 12 months was significantly lower for the fingolimod cohort
      (naive: 31.3%; experienced: 25.7%). Adjusted results found that patients
      receiving self-injected DMTs discontinued significantly sooner than fingolimod
      users. This association was generally stronger in experienced DMT users.
      CONCLUSIONS: Fingolimod initiators were more compliant, less likely to
      discontinue treatment, and discontinued later than patients who initiated self
      injected DMT.

PMID- 24093543
TI  - Current pharmacological concepts for wise use of echinocandins in the treatment
      of Candida infections in septic critically ill patients.
AB  - Candida infections represent challenging causes of severe sepsis and/or of septic
      shock in the critically ill patients. Knowledge of current pharmacological
      concepts may promote a more wise use of echinocandins in the management of
      Candida infections in this setting. Echinocandins have some advantages over
      azoles, both pharmacodynamically (rapid fungicidal activity, anti-biofilm
      activity, unmodified activity against Candida isolates with decreased
      susceptibility to azoles and anti-cytokine/anti-chemokine activity) and
      pharmacokinetically (low interindividual variability, low potential for drug-drug
      interactions), that may influence the timing and the choice of therapy of Candida
      diseases in the critically ill patients. However, concerns exist in regards to
      the feasibility of fixed dosing regimens of echinocandins in all of the different
      patient populations and in regards to the effectiveness of echinocandin
      monotherapy in some clinical settings. In presence of deep-seated infections,
      voriconazole or liposomal amphotericin B may be valuable alternatives or add-on
      therapy. 

PMID- 24093544
TI  - Proportionate reduction in uncertainty of late onset infection in pre-term
      infants by neutrophil CD64 measurement.
AB  - OBJECTIVE: Establish how neutrophil CD64 performs as a marker of definite
      infection in pre-term infants in comparison to C reactive protein (CRP) and
      procalcitonin (PCT). METHODS: A total of 38 pre-term infants with suspected late
      onset infection had CD64 measured by flow cytometry. Proportionate reduction in
      uncertainty (PRU) curves were generated for CD64 counts at various threshold
      values. RESULTS: PRU curves reduced the residual uncertainty of the presence of
      infection by up to 64%. CONCLUSIONS: The CD64 appears to be a useful point of
      care test (POCT) for further defining the likelihood of infection and performs
      better than CRP or PCT at helping to rule in infection.

PMID- 24093545
TI  - Congenital cystic adenomatoid malformation with associated mucinous
      bronchioloalveolar carcinoma in a neonate.
AB  - Congenital cystic adenomatoid malformation (CCAM) of lung is a rare hamartomatous
      disorder characterized by abnormal branching morphogenesis of the lung. We report
      an unusual case of a 2-day-old male newborn with a pulmonary cystic lesion and
      lobectomy revealed a CCAM of the lung that has overlapping features of type 1 and
      type 2, complicating with multifocal mucinous bronchioloalveolar carcinoma (BAC).
      The case indicates that malignant transformation can occur in very early stage of
      the infancy in the patients with CCAM of lung. 

PMID- 24093546
TI  - Nuclear magnetic biosignatures in the carbonaceous matter of ancient cherts:
      comparison with carbonaceous meteorites.
AB  - The search for organic biosignatures is motivated by the hope of understanding
      the conditions of emergence of life on Earth and the perspective of finding
      traces of extinct life in martian sediments. Paramagnetic radicals, which exist
      naturally in amorphous carbonaceous matter fossilized in Precambrian cherts, were
      used as local structural probes and studied by electron paramagnetic resonance
      (EPR) spectroscopy. The nuclear magnetic resonance transitions of elements inside
      and around these radicals were detected by monitoring the nuclear modulations of
      electron spin echo in pulsed EPR. We found that the carbonaceous matter of
      fossilized microorganisms with age up to 3.5 billion years gives specific nuclear
      magnetic signatures of hydrogen (1H), carbon (13C), and phosphorus (31P) nuclei.
      We observed that these potential biosignatures of extinct life are found neither
      in the carbonaceous matter of carbonaceous meteorites (4.56 billion years), the
      most ancient objects of the Solar System, nor in any carbonaceous matter
      resulting from carbonization of organic and bioorganic precursors. These results
      indicate that these nuclear signatures are sensitive to thermal episodes and can
      be used for Archean cherts with metamorphism not higher than the greenschist
      facies.

PMID- 24093547
TI  - Penetration profile and human cadaver skin distribution of finasteride from
      vesicular nanocarriers.
AB  - The skin accumulation of therapeutic agents affects the efficiency of topical
      drug delivery. In this study, in vitro distribution of finasteride of ethosomes
      and liposomes in human cadaver skin after percutaneous delivery were
      investigated. Experiments were performed using modified Franz diffusion cells.
      Finasteride ethosomes, liposomes or hydroethanolic solutions were used as donor
      medium. Drug distribution at different skin layers and depths were studied by
      hotplate separation and frozen horizontal slicing technique. The result showed
      that the accumulation of finasteride in skin ranged from 9.7-24.3 MUg/cm2 at 12
      or 24 hours. The ethosomes demonstrated better enhancing ability to deliver
      finasteride into the dermis layer than liposomes did. The finasteride
      concentration in the dermis layer from ethosomes was more than sevenfold higher
      than from liposomes. The finasteride accumulation in ethosomes group showed a
      distinctive reversed distribution profile. This distinctive reversed distribution
      profile is meaningful for exerting a favorable pharmacological effect for
      finasteride. The drug distribution profile in skin layers showed no significant
      difference between 12 and 24 hours application (p > 0.05). The study demonstrated
      that finasteride can be accumulated at target site more effectively and
      maintained at higher level through the application of novel ethosomal carriers.

PMID- 24093548
TI  - Flanking sequence context-dependent transcription factor binding in early
      Drosophila development.
AB  - BACKGROUND: Gene expression in the Drosophila embryo is controlled by functional
      interactions between a large network of protein transcription factors (TFs) and
      specific sequences in DNA cis-regulatory modules (CRMs). The binding site
      sequences for any TF can be experimentally determined and represented in a
      position weight matrix (PWM). PWMs can then be used to predict the location of TF
      binding sites in other regions of the genome, although there are limitations to
      this approach as currently implemented. RESULTS: In this proof-of-principle
      study, we analyze 127 CRMs and focus on four TFs that control transcription of
      target genes along the anterio-posterior axis of the embryo early in development.
      For all four of these TFs, there is some degree of conserved flanking sequence
      that extends beyond the predicted binding regions. A potential role for these
      conserved flanking sequences may be to enhance the specificity of TF binding, as
      the abundance of these sequences is greatly diminished when we examine only
      predicted high-affinity binding sites. CONCLUSIONS: Expanding PWMs to include
      sequence context-dependence will increase the information content in PWMs and
      facilitate a more efficient functional identification and dissection of CRMs.

PMID- 24093549
TI  - Assessment of the caudate nucleus and its relation to route learning in both
      congenital and late blind individuals.
AB  - BACKGROUND: In the absence of visual input, the question arises as to how complex
      spatial abilities develop and how the brain adapts to the absence of this
      modality. As such, the aim of the current study was to investigate the
      relationship between visual status and an important brain structure with a well
      established role in spatial cognition and navigation, the caudate nucleus. We
      conducted a volumetric analysis of the caudate nucleus in congenitally and late
      blind individuals, as well as in matched sighted control subjects. RESULTS: No
      differences in the volume of the structure were found either between congenitally
      blind (CB) and matched sighted controls or between late blind (LB) and matched
      sighted controls. Moreover, contrary to what was expected, no significant
      correlation was found between caudate volume and performance in a spatial
      navigation task. Finally, consistent with previously published reports, the
      volume of the caudate nucleus was found to be negatively correlated with age in
      the sighted; however such correlations were not significant in the blind groups.
      CONCLUSION: Although there were no group differences, the absence of an age
      volume correlation in the blind suggests that visual deprivation may still have
      an effect on the developmental changes that occur in the caudate nucleus.

PMID- 24093551
TI  - Brain activity associated with placebo suppression of the urge-to-cough in
      humans.
AB  - RATIONALE: Antitussive therapies are accompanied by a substantial placebo effect,
      indicating that inhibitory circuits in the brain have a significant capacity to
      regulate cough neural processing. However, essentially nothing is known about the
      identity of these inhibitory circuits or how they reduce coughing. Understanding
      these processes may help develop more effective antitussive therapies in the
      future. OBJECTIVES: To identify regional changes in human brain activity related
      to the urge-to-cough after placebo antitussive administration. METHODS: Seventeen
      healthy participants undertook functional magnetic resonance imaging while
      completing a series of inhalations of capsaicin to induce the urge-to-cough. The
      resultant brain responses associated with capsaicin inhalation without any
      treatment were compared with those induced by capsaicin after placebo antitussive
      administration. MEASUREMENTS AND MAIN RESULTS: There was a significant decrease
      in participants' ratings of urge-to-cough after the placebo antitussive
      administration. Brain activity associated with capsaicin inhalation was less in
      the somatosensory, primary motor, insula, and cingulate cortices during placebo
      antitussive trials compared with no treatment control subjects. By contrast,
      placebo trials were associated with increased activation in the prefrontal and
      left parietal cortices. CONCLUSIONS: Placebo-related decreases in urge-to-cough
      are accompanied by commensurate decreases in several brain regions activated
      during capsaicin inhalation, suggesting that beliefs about treatment can modify
      the central processing of inputs arising from the airways. The prefrontal cortex
      and posterior parietal cortex are likely to play an active role in the
      modification of airway sensory processing after administration of a placebo.

PMID- 24093550
TI  - Hyperglycemia induces differential change in oxidative stress at gene expression
      and functional levels in HUVEC and HMVEC.
AB  - BACKGROUND: Endothelial dysfunction precedes pathogenesis of vascular
      complications in diabetes. In recent years, the mechanisms of endothelial
      dysfunction were investigated to outline strategies for its treatment. However,
      the therapies for dysfunctional endothelium resulted in multiple clinical trial
      failures and remain elusive. There is a need for defining hyperglycemia-induced
      endothelial dysfunction with both generic and specific dysfunctional changes in
      endothelial cells (EC) using a systems approach. In this study, we investigated
      hyperglycemia-induced endothelial dysfunction in HUVEC and HMVEC. We investigated
      hyperglycemia-induced functional changes (superoxide (O2-), and hydrogen peroxide
      (H2O2) production and mitochondrial membrane polarization) and gene expression
      fingerprints of related enzymes (nitric oxide synthase, NAD(P)H oxidase, and
      reactive oxygen species (ROS) neutralizing enzymes) in both ECs. METHOD: Gene
      expression of NOS2, NOS3, NOX4, CYBA, UCP1, CAT, TXNRD1, TXNRD2, GPX1, NOX1,
      SOD1, SOD2, PRDX1, 18s, and RPLP0 were measured using real-time PCR. O2-
      production was measured with dihydroethidium (DHE) fluorescence measurement. H2O2
      production was measured using Amplex Red assay. Mitochondrial membrane
      polarization was measured using JC-10 based fluorescence measurement. RESULTS: We
      showed that the O2- levels increased similarly in both ECs with hyperglycemia.
      However, these endothelial cells showed significantly different underlying gene
      expression profile, H2O2 production and mitochondrial membrane polarization. In
      HUVEC, hyperglycemia increased H2O2 production, and hyperpolarized mitochondrial
      membrane. ROS neutralizing enzymes SOD2 and CAT gene expression were
      downregulated. In contrast, there was an upregulation of nitric oxide synthase
      and NAD(P)H oxidase and a depolarization of mitochondrial membrane in HMVEC. In
      addition, ROS neutralizing enzymes SOD1, GPX1, TXNRD1 and TXNRD2 gene expression
      were significantly upregulated in high glucose treated HMVEC. CONCLUSION: Our
      findings highlighted a unique framework for hyperglycemia-induced endothelial
      dysfunction. We showed that multiple pathways are differentially affected in
      these endothelial cells in hyperglycemia. High occurrences of gene expression
      changes in HMVEC in this study supports the hypothesis that microvasculature
      precedes macrovasculature in epigenetic regulation forming vascular metabolic
      memory. Identifying genomic phenotype and corresponding functional changes in
      hyperglycemic endothelial dysfunction will provide a suitable systems biology
      approach for understanding underlying mechanisms and possible effective
      therapeutic intervention.

PMID- 24093552
TI  - Micronutrient supplementation and T cell-mediated immune responses in patients
      with tuberculosis in Tanzania.
AB  - Limited studies exist regarding whether incorporating micronutrient supplements
      during tuberculosis (TB) treatment may improve cell-mediated immune response. We
      examined the effect of micronutrient supplementation on lymphocyte proliferation
      response to mycobacteria or T-cell mitogens in a randomized trial conducted on
      423 patients with pulmonary TB. Eligible participants were randomly assigned to
      receive a daily dose of micronutrients (vitamins A, B-complex, C, E, and
      selenium) or placebo at the time of initiation of TB treatment. We found no
      overall effect of micronutrient supplements on lymphocyte proliferative responses
      to phytohaemagglutinin or purified protein derivatives in HIV-negative and HIV
      positive TB patients. Of HIV-negative TB patients, the micronutrient group tended
      to show higher proliferative responses to concanavalin A than the placebo group,
      although the clinical relevance of this finding is not readily notable. The role
      of nutritional intervention in this vulnerable population remains an important
      area of future research.

PMID- 24093553
TI  - Visualizing chemical structure-subcellular localization relationships using
      fluorescent small molecules as probes of cellular transport.
AB  - BACKGROUND: To study the chemical determinants of small molecule transport inside
      cells, it is crucial to visualize relationships between the chemical structure of
      small molecules and their associated subcellular distribution patterns. For this
      purpose, we experimented with cells incubated with a synthetic combinatorial
      library of fluorescent, membrane-permeant small molecule chemical agents. With an
      automated high content screening instrument, the intracellular distribution
      patterns of these chemical agents were microscopically captured in image data
      sets, and analyzed off-line with machine vision and cheminformatics algorithms.
      Nevertheless, it remained challenging to interpret correlations linking the
      structure and properties of chemical agents to their subcellular localization
      patterns in large numbers of cells, captured across large number of images.
      RESULTS: To address this challenge, we constructed a Multidimensional Online
      Virtual Image Display (MOVID) visualization platform using off-the-shelf hardware
      and software components. For analysis, the image data set acquired from cells
      incubated with a combinatorial library of fluorescent molecular probes was sorted
      based on quantitative relationships between the chemical structures,
      physicochemical properties or predicted subcellular distribution patterns. MOVID
      enabled visual inspection of the sorted, multidimensional image arrays: Using a
      multipanel desktop liquid crystal display (LCD) and an avatar as a graphical user
      interface, the resolution of the images was automatically adjusted to the
      avatar's distance, allowing the viewer to rapidly navigate through high
      resolution image arrays, zooming in and out of the images to inspect and annotate
      individual cells exhibiting interesting staining patterns. In this manner, MOVID
      facilitated visualization and interpretation of quantitative structure
      localization relationship studies. MOVID also facilitated direct, intuitive
      exploration of the relationship between the chemical structures of the probes and
      their microscopic, subcellular staining patterns. CONCLUSION: MOVID can provide a
      practical, graphical user interface and computer-assisted image data
      visualization platform to facilitate bioimage data mining and cheminformatics
      analysis of high content, phenotypic screening experiments.

PMID- 24093555
TI  - Catalytic allylation of stabilized phosphonium ylides with primary allylic
      amines.
AB  - A range of ketone-stabilized phosphonium ylides were allylated with high
      regioselectivity by primary allylic amines in the presence of 5 mol % Pd(PPh3)4
      and 10 mol % B(OH)3, and subsequent one-pot Wittig olefination gave structurally
      diverse alpha,beta-unsaturated ketones in good to excellent overall yields with
      excellent E selectivity. The one-pot allylation/olefination reaction was extended
      to ester- and nitrile-stabilized phosphonium ylides by replacing B(OH)3 with
      TsOH, and the corresponding alpha,beta-unsaturated esters and nitriles were
      obtained in moderate overall yields. 

PMID- 24093556
TI  - Copper-catalyzed intermolecular dehydrogenative amidation/amination of quinoline
      N-oxides with lactams/cyclamines.
AB  - C-H, N-H dehydrogenative coupling of quinoline N-oxides with lactams/cyclamines
      has been achieved in the presence of the Cu(OAc)2 catalyst to give good to
      excellent yields. This study provides a new strategy for the construction of a 2
      aminoquinoline skeleton via direct functionalization of aryl C-H bonds. 

PMID- 24093559
TI  - Estimation of 10-year probability bone fracture in a selected sample of
      Palestinian people using fracture risk assessment tool.
AB  - BACKGROUND: The Fracture Risk Assessment (FRAX) tool has been developed by the
      World Health Organization (WHO) to calculate 10-year probability hip fracture
      (HP) or major osteoporotic fracture (MOF). The objective of this study was to
      assess the 10-year probability of MOF and HF among a selected sample of
      Palestinian people. METHODS: A sample of 100 subjects was studied. Dual energy X
      ray absorpitometry was performed to measure bone mineral density (BMD) which was
      then inserted into FRAX Palestine online WHO tool to calculate the 10-year
      probability of MOF and HF. RESULTS: The median age of participants was 61.5 years
      and the majority (79%) were females. The median (interquartile range) of femoral
      hip BMD was 0.82 (0.76-0.92) g/cm2. The mean vertebral and hip T scores were 
      1.41 +/- 0.13 SDs and -0.91 +/- 0.10 SDs respectively. About one fifth of the
      sample (21%) had vertebral osteoporosis and 5% had hip osteoporosis. The median
      (interquartile range) 10-year probability of MOF and HF based on BMD were 3.7
      (2.43-6.18)%, and 0.30 (0.10-0.68)% respectively. CONCLUSION: Osteoporosis is
      common among Palestinian people above 50 years old. Bone fracture prevention
      strategies and research should be a priority in Palestine. Using FRAX might be a
      helpful screening tool in primary healthcare centres in Palestine.

PMID- 24093561
TI  - Dynamic mechanisms in the life cycle of an RNA molecule.

PMID- 24093554
TI  - Age of red blood cells and outcome in acute kidney injury.
AB  - INTRODUCTION: Transfusion of red blood cells (RBCs) and, in particular, older
      RBCs has been associated with increased short-term mortality in critically ill
      patients. We evaluated the association between age of transfused RBCs and acute
      kidney injury (AKI), hospital, and 90-day mortality in critically ill patients.
      METHODS: We conducted a prospective, observational, predefined sub-study within
      the FINNish Acute Kidney Injury (FINNAKI) study. This study included all elective
      ICU admissions with expected ICU stay of more than 24 hours and all emergency
      admissions from September to November 2011. To study the age of RBCs, we
      classified transfused patients into quartiles according to the age of oldest
      transfused RBC unit in the ICU. AKI was defined according to KDIGO (Kidney
      Disease: Improving Global Outcomes) criteria. RESULTS: Out of 1798 patients, 652
      received at least one RBC unit. The median [interquartile range] age of the
      oldest RBC unit transfused was 12 [11-13] days in the freshest quartile and 21
      [17-27] days in the quartiles 2 to 4. On logistic regression, RBC age was not
      associated with the development of KDIGO stage 3 AKI. Patients in the quartile of
      freshest RBCs had lower crude hospital and 90-day mortality rates compared to
      those in the quartiles of older blood. After adjustments, older RBC age was
      associated with significantly increased risk for hospital mortality. Age,
      Simplified Acute Physiology Score II (SAPS II)-score without age points, maximum
      Sequental Organ Failure Assessment (SOFA) score and the total number of
      transfused RBC units were independently associated with 90-day mortality.
      CONCLUSIONS: The age of transfused RBC units was independently associated with
      hospital mortality but not with 90-day mortality or KDIGO stage 3 AKI. The number
      of transfused RBC units was an independent risk factor for 90-day mortality.

PMID- 24093560
TI  - Hispolon induces apoptosis through JNK1/2-mediated activation of a caspase-8, -9,
      and -3-dependent pathway in acute myeloid leukemia (AML) cells and inhibits AML
      xenograft tumor growth in vivo.
AB  - Hispolon is an active phenolic compound of Phellinus igniarius, a mushroom that
      was recently shown to have antioxidant and anticancer activities in various solid
      tumors. Here, the molecular mechanisms by which hispolon exerts anticancer
      effects in acute myeloid leukemia (AML) cells was investigated. The results
      showed that hispolon suppressed cell proliferation in the various AML cell lines.
      Furthermore, hispolon effectively induced apoptosis of HL-60 AML cells through
      caspases-8, -9, and -3 activations and PARP cleavage. Moreover, treatment of HL
      60 cells with hispolon induced sustained activation of JNK1/2, and inhibition of
      JNK by JNK1/2 inhibitor or JNK1/2-specific siRNA significantly abolished the
      hispolon-induced activation of the caspase-8/-9/-3. In vivo, hispolon
      significantly reduced tumor growth in mice with HL-60 tumor xenografts. In
      hispolon-treated tumors, activation of caspase-3 and a decrease in Ki67-positive
      cells were observed. Our results indicated that hispolon may have the potential
      to serve as a therapeutic tool to treat AML. 

PMID- 24093563
TI  - A 4-week-old boy with emesis and pale stools (Case Presentation).

PMID- 24093565
TI  - Assessing synovitis based on dynamic gadolinium-enhanced MRI and EULAR-OMERACT
      scores of the wrist in patients with rheumatoid arthritis.
AB  - OBJECTIVES: The objective of this study was to correlate dynamic contrast
      enhanced MRI (DCE-MRI) perfusion parameters and conventional MRI scored with
      RAMRIS acquired from the wrists of patients with rheumatoid arthritis (RA).
      METHODS: Fifty-nine RA patients had conventional and DCE-MRI of the wrist using a
      low-field 0.2T ESAOTE extremity scanner. Synovitis, bone oedema and bone erosions
      were assessed using RAMRIS. DCE-MRI data were analysed using dedicated software
      Dynamika resulting in a set of perfusion parameters. RESULTS: RAMRIS synovitis
      score and the number of enhancing pixels in DCE-MRI images have shown significant
      correlation. In this study, the parameters reflecting the dynamics of MRI signal
      enhancement (maximum enhancement, initial enhancement rate and the time of onset
      of enhancement) did not correlate with RAMRIS synovitis score, with bone oedema
      and with bone erosions scores. CONCLUSIONS: One-way analysis of variance leads to
      conclusions consistent with the correlation analysis. There were cases of
      inflammation seen in axial images of a 3D T1-weighed gradient echo sequence not
      reflected in the perfusion data.

PMID- 24093567
TI  - Intracranial stereotactic radiosurgery: concepts and techniques.
AB  - Stereotactic radiosurgery was conceptualized to treat functional diseases of the
      brain. The need for devices capable of molding the radiation dose to the nuances
      of intracranial lesions and yet preserve brain function became a challenge.
      Several devices capable of performing radiosurgery of high quality became
      commercially available, each with advantages and disadvantages. Speed of
      radiosurgery delivery for cost effectiveness and comfort for the patient are
      currently the main developments in the field. Nuances of these devices,
      procedural steps of radiosurgery, and the team approach of radiosurgery are
      discussed in this article. 

PMID- 24093566
TI  - Adhesion maturation of neutrophils on nanoscopically presented platelet
      glycoprotein Ibalpha.
AB  - Neutrophilic granulocytes play a fundamental role in cardiovascular disease. They
      interact with platelet aggregates via the integrin Mac-1 and the platelet
      receptor glycoprotein Ibalpha (GPIbalpha). In vivo, GPIbalpha presentation is
      highly variable under different physiological and pathophysiological conditions.
      Here, we quantitatively determined the conditions for neutrophil adhesion in a
      biomimetic in vitro system, which allowed precise adjustment of the spacings
      between human GPIbalpha presented on the nanoscale from 60 to 200 nm. Unlike most
      conventional nanopatterning approaches, this method provided control over the
      local receptor density (spacing) rather than just the global receptor density.
      Under physiological flow conditions, neutrophils required a minimum spacing of
      GPIbalpha molecules to successfully adhere. In contrast, under low-flow
      conditions, neutrophils adhered on all tested spacings with subtle but nonlinear
      differences in cell response, including spreading area, spreading kinetics,
      adhesion maturation, and mobility. Surprisingly, Mac-1-dependent neutrophil
      adhesion was very robust to GPIbalpha density variations up to 1 order of
      magnitude. This complex response map indicates that neutrophil adhesion under
      flow and adhesion maturation are differentially regulated by GPIbalpha density.
      Our study reveals how Mac-1/GPIbalpha interactions govern cell adhesion and how
      neutrophils process the number of available surface receptors on the nanoscale.
      In the future, such in vitro studies can be useful to determine optimum
      therapeutic ranges for targeting this interaction. 

PMID- 24093568
TI  - Stereotactic radiosurgery of intracranial meningiomas.
AB  - Stereotactic radiosurgery (SRS) has been performed for intracranial meningiomas
      for more than 30 years. Small to moderate-sized meningiomas are generally
      considered good candidates for SRS because of their neuro-imaging and
      radiobiological characteristics. Patient selection is critical for successful
      meningioma SRS. Factors related to tumor control and radiation-related
      complications in patients with WHO grade I or presumed meningiomas include
      history of prior surgery, tumor volume, and tumor location. Patients with small
      volume, nonoperated skull-base or tentorial meningiomas typically have the best
      outcomes after SRS.

PMID- 24093569
TI  - Stereotactic radiosurgery of pituitary adenomas.
AB  - The goal of pituitary adenoma radiosurgery is to halt tumor growth, normalize
      hormonal hypersecretion if present, maintain normal pituitary function, and
      preserve important structures around the sella. The radiation dose necessary to
      stop tumor growth is lower than the dose necessary to achieve normalization of
      hormonal hypersecretion. The minimum distance required between the irradiated
      target and the optic pathway should be 2 mm for secreting adenomas, but in cases
      of nonsecreting adenomas this distance is even lower. The current role of
      radiosurgery in most cases is as an adjuvant treatment of residual or recurrent
      adenomas after previous microsurgery.

PMID- 24093570
TI  - Radiosurgery for vestibular schwannomas.
AB  - This article investigates the role of radiosurgery and stereotactic radiotherapy
      in the management of vestibular schwannomas (VS), reviewing the authors' own
      prospective cohort and the current literature. For patients with large Stage IV
      VS (according to the Koos classification), a combined approach with deliberate
      partial microsurgical removal followed by radiosurgery to the residual tumor is
      proposed. The authors' cohort is unique with respect to the size of the
      population and the length of the follow-up, and demonstrates the efficacy and
      safety of VS radiosurgery, with particular regard to its high rate of hearing
      preservation. 

PMID- 24093571
TI  - Stereotactic radiosurgery for nonvestibular schwannomas.
AB  - This article summarizes tumor control and functional outcomes of stereotactic
      radiosurgery (SRS) for patients with nonvestibular schwannomas, in comparison
      with those treated with microsurgical resection. To date, surgical resection has
      been a common treatment for nonvestibular schwannomas. Because these tumors are
      generally benign, complete tumor resection is a desirable curative treatment.
      However, it is almost infeasible to completely remove these tumors without any
      complications, even for experienced neurosurgeons, because of adherence to
      surrounding critical structures such as cranial nerves, brainstem, or vessels.
      SRS provides a good tumor control rate with much less morbidity than
      microsurgical resection. 

PMID- 24093572
TI  - Multi-session radiosurgery of benign intracranial tumors.
AB  - Multi-session stereotactic radiosurgery (SRS) enables a high dose per fraction to
      be delivered to the tumor bed with rapid dose falloff that allows for sparing of
      critical structures, resulting in less radiation-associated toxicity. In this
      article, the authors review the basic concepts and techniques of multi-session
      SRS, indications for this technique, outcomes from single-session and multi
      session SRS using 3 commonly treated benign intracranial tumors (meningiomas,
      vestibular schwannomas, pituitary adenomas), and discuss why multi-session SRS is
      an attractive approach for the treatment of these tumors. 

PMID- 24093573
TI  - Stereotactic radiosurgery of intracranial chordomas, chondrosarcomas, and glomus
      tumors.
AB  - Chordomas and chondrosarcomas are rare, slow-glowing, locally aggressive tumors
      with high recurrence rates. Stereotactic radiosurgery (SRS) is an important
      management option for patients with recurrent or residual chordomas and
      chondrosarcomas. Glomus jugulare tumor are rare highly vascularized tumors that
      arise from the paraganglionic structures of the glossopharyngeal and vagal
      nerves. Because of their highly vascular nature and surgically formidable
      anatomic location, curative resection often proves challenging. SRS can be used
      as an up-front treatment or as an additional treatment for patients with
      recurrent or residual glomus jugulare tumor after surgical resection. 

PMID- 24093574
TI  - Stereotactic radiosurgery of intracranial arteriovenous malformations.
AB  - Stereotactic radiosurgery for intracranial arteriovenous malformations (AVMs) has
      been performed since the 1970s. When an AVM is treated with radiosurgery,
      radiation injury to the vascular endothelium induces the proliferation of smooth
      muscle cells and the elaboration of extracellular collagen, which leads to
      progressive stenosis and obliteration of the AVM nidus. Obliteration after AVM
      radiosurgery ranges from 60% to 80%, and relates to the size of the AVM and the
      prescribed radiation dose. The major drawback of radiosurgical AVM treatment is
      the risk of bleeding during the latent period (typically 2 years) between
      treatment and AVM thrombosis.

PMID- 24093575
TI  - Stereotactic radiosurgery of intracranial cavernous malformations.
AB  - Despite increasing worldwide experience, the role of stereotactic radiosurgery
      (SRS) in the management of cerebral cavernous malformations (CMs) remains
      controversial. Microsurgical excision of easily accessible CMs is typically safe;
      therefore, removal remains the gold standard for most of the symptomatic
      hemispheric lesions. However, there is now sufficient evidence supporting the use
      of SRS for the difficult cases. Waiting for the cumulative morbidity of the
      natural history to justify intervention does not serve the patient's interest,
      therefore, we argue for early radiosurgical intervention. Carefully designed
      randomized controlled trials might resolve controversies concerning the role of
      SRS in treating cerebral CMs. 

PMID- 24093576
TI  - Stereotactic radiosurgery of intracranial dural arteriovenous fistulas.
AB  - Depending on their location and angioarchitecture, intracranial dural
      arteriovenous fistulas (dAVF) pose various neurologic symptoms as well as a risk
      of intracranial hemorrhage. Stereotactic radiosurgery (SRS), microsurgery, and
      embolization play a role in the management of dAVF patients, and, at times,
      patients undergo a combination of approaches. Comparable to arteriovenous
      malformations, SRS offers a reasonable rate of angiographic obliteration and
      symptomatic improvement in selected patients with dAVF. Complications after SRS
      of dAVF are uncommon and generally manageable. Patients remain at risk for
      intracranial hemorrhage until the dAVF is completely obliterated. 

PMID- 24093577
TI  - Stereotactic radiosurgery for brain metastases.
AB  - The authors discuss the results of Gamma Knife (Elekta AB, Stockholm, Sweden)
      radiosurgery (GKS) for brain metastases based on their retrospective review of
      2645 cases. All patients were treated according to the same protocol, with the
      tumors being irradiated with GKS without up-front whole-brain radiation therapy
      at the initial treatment. New distant lesions, detected by gadolinium-enhanced
      magnetic resonance imaging (MRI) performed every 2 to 3 months, were treated
      primarily with GKS. New distant lesions are generally well controlled with GKS
      salvage treatment. However, careful observation with enhanced MRI and appropriate
      salvage treatments are needed to prevent neurologic death and maintain activities
      of daily life.

PMID- 24093578
TI  - Stereotactic radiosurgery for intracranial gliomas.
AB  - This article presents an overview of stereotactic radiosurgery for intracranial
      glioma. It assists readers in reviewing up-to-date literature on this topic and
      determining indications of radiosurgery in the treatment of glioma. Discussion
      also includes its recent advances and future perspectives. 

PMID- 24093579
TI  - Radiosurgical management of trigeminal neuralgia.
AB  - Over the past several decades, stereotactic radiosurgery has become a viable
      noninvasive treatment option for patients with trigeminal neuralgia. The
      scientific literature regarding the radiosurgical treatment of trigeminal
      neuralgia has evolved to identify factors that predict both efficacy and
      toxicity. Radiosurgical management has, thus, become complementary to medical
      management, microvascular decompression, and percutaneous ablative procedures.
      Thus, effective management often requires multidisciplinary collaboration. The
      intent of this review is to discuss the role of radiosurgery in the modern
      management of trigeminal neuralgia and to review radiosurgical outcomes,
      targeting, and controversies. 

PMID- 24093580
TI  - Stereotactic radiosurgery for epilepsy and functional disorders.
AB  - Stereotactic radiosurgery is used for many indications. In functional
      neurosurgery, it is used to modulate the function of axons, neurons, and related
      brain circuits. In this article, indications, current techniques, and outcomes
      are discussed. 

PMID- 24093581
TI  - Intracranial stereotactic radiosurgery.

PMID- 24093583
TI  - Hyaluronic acid-based hydrogels containing covalently integrated drug depots:
      implication for controlling inflammation in mechanically stressed tissues.
AB  - Synthetic hydrogels containing covalently integrated soft and deformable drug
      depots capable of releasing therapeutic molecules in response to mechanical
      forces are attractive candidates for the treatment of degenerated tissues that
      are normally load bearing. Herein, radically cross-linkable block copolymer
      micelles (xBCM) assembled from an amphiphilic block copolymer consisting of
      hydrophilic poly(acrylic acid) (PAA) partially modified with 2-hydroxyethyl
      acrylate, and hydrophobic poly(n-butyl acryclate) (PnBA) were employed as the
      drug depots and the microscopic cross-linkers for the preparation of hyaluronic
      acid (HA)-based, hydrogels. HA hydrogels containing covalently integrated
      micelles (HAxBCM) were prepared by radical polymerization of glycidyl
      methacrylate (GMA)-modified HA (HAGMA) in the presence of xBCMs. When micelles
      prepared from the parent PAA-b-PnBA without any polymerizable double bonds were
      used, hydrogels containing physically entrapped micelles (HApBCM) were obtained.
      The addition of xBCMs to a HAGMA precursor solution accelerated the gelation
      kinetics and altered the hydrogel mechanical properties. The resultant HAxBCM
      gels exhibit an elastic modulus of 847 +/- 43 Pa and a compressive modulus of 9.2
      +/- 0.7 kPa. Diffusion analysis of Nile Red (NR)-labeled xBCMs employing
      fluorescence correlation spectroscopy confirmed the covalent immobilization of
      xBCMs in HA networks. Covalent integration of dexamethasone (DEX)-loaded xBCMs in
      HA gels significantly reduced the initial burst release and provided sustained
      release over a prolonged period. Importantly, DEX release from HAxBCM gels was
      accelerated by intermittently applied external compression in a strain-dependent
      manner. Culturing macrophages in the presence of DEX-releasing HAxBCM gels
      significantly reduced cellular production of inflammatory cytokines.
      Incorporating mechano-responsive modules in synthetic matrices offers a novel
      strategy to harvest mechanical stress present in the healing wounds to initiate
      tissue repair. 

PMID- 24093584
TI  - Vitamin D deficiency in Egyptian mothers and their neonates and possible related
      factors.
AB  - OBJECTIVE: To correlate vitamin D level in Egyptian mothers with that of their
      newborns, and examine risk factors related to maternal vitamin D deficiency.
      METHODS: A cross-sectional study was carried out at the university teaching
      hospital in Cairo, Egypt. Serum 25(OH) D levels were measured by enzyme-linked
      immunosorbent assay in 135 pregnant women at >=37 weeks' gestation immediately
      before delivery and in cord blood of their newborns. RESULTS: The levels of serum
      25(OH) D were 32.6 +/- 21.4 ng/ml in mothers and 16.7 +/- 10 ng/ml in their
      newborns. Maternal vitamin D level was strongly correlated with that of the
      newborns (r = 0.7, p < 0.0001). Maternal vitamin D deficiency/insufficiency and
      neonatal vitamin D deficiency/insufficiency were encountered in (40%, 28.9% and
      60%, 32.6% respectively). Maternal vitamin D levels showed significant
      correlations with maternal body mass index (BMI; r = -0.201, p = 0.021),
      gestational age at delivery (r = 0.315, p <= 0.0001), fish consumption (r =
      0.185, p = 0.032), educational level (r = 0.29, p = 0.001), and skin exposure (r
      = 0.247, p = 0.004). CONCLUSION: Maternal vitamin D levels strongly correlate
      with neonatal levels. Maternal vitamin D deficiency is a real problem in Egypt;
      this is generally related to high BMI, low fish consumption, low educational
      level, and limited skin exposure.

PMID- 24093582
TI  - Modeling of the hypothalamic-pituitary-adrenal axis-mediated interaction between
      the serotonin regulation pathway and the stress response using a Boolean
      approximation: a novel study of depression.
AB  - Major depressive disorder (MDD) is a multifactorial disorder known to be
      influenced by both genetic and environmental factors. MDD presents a heritability
      of 37%, and a genetic contribution has also been observed in studies of family
      members of individuals with MDD that imply that the probability of suffering the
      disorder is approximately three times higher if a first-degree family member is
      affected. Childhood maltreatment and stressful life events (SLEs) have been
      established as critical environmental factors that profoundly influence the onset
      of MDD. The serotonin pathway has been a strong candidate for genetic studies,
      but it only explains a small proportion of the heritability of the disorder,
      which implies the involvement of other pathways. The serotonin (5-HT) pathway
      interacts with the stress response pathway in a manner mediated by the
      hypothalamic-pituitary-adrenal (HPA) axis. To analyze the interaction between the
      pathways, we propose the use of a synchronous Boolean network (SBN)
      approximation. The principal aim of this work was to model the interaction
      between these pathways, taking into consideration the presence of selective
      serotonin reuptake inhibitors (SSRIs), in order to observe how the pathways
      interact and to examine if the system is stable. Additionally, we wanted to study
      which genes or metabolites have the greatest impact on model stability when
      knocked out in silico. We observed that the biological model generated predicts
      steady states (attractors) for each of the different runs performed, thereby
      proving that the system is stable. These attractors changed in shape, especially
      when anti-depressive drugs were also included in the simulation. This work also
      predicted that the genes with the greatest impact on model stability were those
      involved in the neurotrophin pathway, such as CREB, BDNF (which has been
      associated with major depressive disorder in a variety of studies) and TRkB,
      followed by genes and metabolites related to 5-HT synthesis. 

PMID- 24093586
TI  - Intra- and intermolecular hydrogen bonds in pyrrolylindandione derivatives and
      their interaction with fluoride and acetate: possible anion sensing properties.
AB  - The series of push-pull compounds containing the pyrrole ring as a donor and the
      1,3-indandione derived moieties as the acceptor unit were synthesized, and strong
      intramolecular hydrogen bonding in their molecules was studied. In the presence
      of fluoride and acetate anions their solutions undergo color changes. It was
      shown by NMR, UV-vis, and quantum chemical calculations including AIM analysis
      that all these compounds undergo solvent-assisted rupture of the intramolecular
      hydrogen bond followed by the formation of a strong intermolecular hydrogen bond
      with fluoride and acetate anions which finally abstract a proton from the pyrrole
      ring. The insensitivity of the studied compounds to other anions (Cl, Br, HSO4,
      PF6) is consequence of the instability of the corresponding hydrogen-bonded
      complexes. 

PMID- 24093585
TI  - Change in heart rate variability precedes the occurrence of periodic leg
      movements during sleep: an observational study.
AB  - BACKGROUND: Several reports have described that individual periodic leg movements
      during sleep (PLMS) activities are associated with autonomic nervous system
      activity occurring shortly before each PLMS activity. Nevertheless, no study has
      investigated dynamic changes of autonomic nervous system activity before the
      onset of PLMS. This study detected changes in heart rate variability (HRV) at the
      onset of the period with PLMS using complex demodulation method. METHODS: This
      study enrolled 14 patients diagnosed as having idiopathic PLMS disorder (PLMD).
      In periods with and without PLMS during sleep stage 2, HRV-related variables and
      the spectral power of fluctuation of a high frequency (HF) band (FHFB) were
      analyzed and compared. The changes of those parameters during transition from the
      period without PLMS to that with PLMS were explored. RESULTS: Spectral power in
      the low frequency (LF) band and very low frequency (VLF) band were higher in the
      period with PLMS. Additionally, the average frequency in FHFB was higher. The
      frequency in this band fluctuated during the period with PLMS with remarkable
      elevation of FHFB. Moreover, spectral powers in FHFB, LF, and VLF were remarkably
      elevated shortly before the beginning of the period with PLMS (FHFB, -65 s; LF, 
      53 s; and VLF, -45 s). CONCLUSIONS: Elevation of sympathetic nervous system
      activity and mean frequency fluctuation in an HF band can occur several tens of
      seconds before the period with PLMS. Dynamic changes in the autonomic nervous
      system activity might be related to the vulnerability to PLMS occurrence during
      the night.

PMID- 24093587
TI  - How great is the risk of Middle East respiratory syndrome coronavirus to the
      global population?

PMID- 24093588
TI  - Differential pressure in shunt therapy: investigation of position-dependent
      intraperitoneal pressure in a porcine model.
AB  - OBJECT: The differential pressure between the intracranial and intraperitoneal
      cavities is essential for ventriculoperitoneal shunting. A determination of the
      pressure in both cavities is decisive for selecting the appropriate valve type
      and opening pressure. The intraperitoneal pressure (IPP)-in contrast to the
      intracranial pressure-still remains controversial with regard to its normal level
      and position dependency. METHODS: The authors used 6 female pigs for the
      experiments. Two transdermal telemetric pressure sensors (cranial and caudal)
      were implanted intraperitoneally with a craniocaudal distance of 30 cm. Direct
      IPP measurements were supplemented with noninvasive IPP measurements
      (intragastral and intravesical). The IPP was measured with the pigs in the supine
      (0 degrees ), 30 degrees , 60 degrees , and vertical (90 degrees ) body
      positions. After the pigs were euthanized, CT was used to determine the
      intraperitoneal probe position. RESULTS: With pigs in the supine position, the
      mean (+/- SD) IPP was 10.0 +/- 3.5 cm H2O in a mean vertical distance of 4.5 +/-
      2.8 cm to the highest level of the peritoneum. The difference between the mean
      IPP of the cranially and the caudally implanted probes (Delta IPP) increased
      according to position, from 5.5 cm H2O in the 0 degrees  position to 11.5 cm H2O
      in the 30 degrees  position, 18.3 cm H2O in the 60 degrees  position, and 25.6 cm
      H2O in the vertical body position. The vertical distance between the probe tips
      (cranially implanted over caudally implanted) increased 3.4, 11.2, 19.3, and 22.3
      cm for each of the 4 body positions, respectively. The mean difference between
      the Delta IPP and the vertical distance between both probe tips over all body
      positions was 1.7 cm H2O. CONCLUSIONS: The IPP is subject to the position
      dependent hydrostatic force. Normal IPP is able to reduce the differential
      pressure in patients with ventriculoperitoneal shunts.

PMID- 24093589
TI  - Pallidal deep brain stimulation for dystonia: a case series.
AB  - OBJECT: Pallidal deep brain stimulation (DBS) is a treatment option for those
      with early-onset dystonia. However, there are limited data on long-term outcome
      and treatment complications. The authors report on the short- and long-term
      effects of pallidal DBS in a cohort of patients with early-onset dystonia.
      METHODS: Fourteen consecutive pediatric patients with early-onset dystonia were
      systematically evaluated and treated. The duration of follow-up ranged from 16 to
      84 months. RESULTS: There were no immediate postoperative complications. At last
      follow-up, 12 of the 14 patients displayed a significant decline in the Burke
      Fahn-Marsden Dystonia Rating Scale motor subscale score, with an average decrease
      of 62% +/- 8.4%. The most common hardware complication was lead fracture (14.3%).
      CONCLUSIONS: These data provide further evidence that DBS is a safe and effective
      treatment for those with earlyonset dystonia.

PMID- 24093590
TI  - Routine preoperative blood testing in pediatric neurosurgery.
AB  - OBJECT: The frequency with which routine preoperative blood test results predict
      perioperative or postoperative complications is insignificant. The unnecessary
      ordering of routine tests increases the financial costs and patients' distress.
      The authors evaluated the effects of routine preoperative testing on patient
      management and the overall financial costs. METHODS: The authors retrospectively
      reviewed the medical records and laboratory data for 355 children admitted to the
      neurosurgical department for elective procedures over a 5-year period (January
      2008-December 2012). They excluded all patients admitted for imaging or surgical
      procedures requiring local anesthesia, and they recorded the results of
      preoperative and previous (up to 6 months before surgery) blood tests and any
      abnormalities noted. RESULTS: As a result of the 3489 blood tests ordered
      preoperatively for 328 (94.6%) of the 355 patients, 29 abnormalities (9%) were
      detected. Most of these abnormal values were near the reference range, and none
      significantly affected the progression of scheduled procedures. For only 1
      patient (0.28%) was the procedure cancelled because of an abnormality
      (preoperative partial thromboplastin time), which further testing showed to be a
      false-positive result. The cost of these tests over 5 years was 5205-10,410 euros
      ($6766-$13,533 US). CONCLUSIONS: Preoperative tests should be selectively
      requested on the basis of clinical indication.

PMID- 24093591
TI  - Intracerebral foreign body granuloma caused by a resorbable plate with passive
      intraosseous translocation after cranioplasty.
AB  - Numerous reports have demonstrated the usefulness of bioresorbable materials, but
      few have described severe complications caused by delayed degradation. The
      authors present the case of an intracranial foreign body granuloma caused by
      plates made of unsintered hydroxyapatite (uHA) particles and poly-l-lactide
      (PLLA; Super Fixsorb MX, Takiron) after cranioplasty. This 1-month-old boy
      presented to the authors' department with Pfeiffer syndrome. He had multiple
      suture synostosis causing turribrachycephaly, Chiari malformation Type 1, and
      obstructive sleep apnea syndrome. At 6 months old, the child was treated with
      multidirectional cranial distraction osteogenesis. The uHA-PLLA plates were
      applied as base stones to reinforce the pins. After 16 days of distraction and 3
      weeks of consolidation, the pins were removed. Seventeen months postoperatively,
      the plate on the right temporal bone showed passive intraosseous translocation
      (PIT), and by 2 years postoperatively, the plate was completely left behind in
      the cerebrum. At 3.5 years postoperatively, MRI disclosed a contrast-enhanced
      mass with surrounding brain edema at the site of the plate. The lesion was
      resected. The clinical history and histological specimens led to a diagnosis of
      foreign body granuloma surrounding the nonabsorbed resorbable plate in the dura
      mater. Resorbable plates are clearly useful resources in cases in which delayed
      absorption will not prove problematic, but careful application and follow-up is
      required when dealing with the growing skull given the possibility of
      intracranial displacement after PIT. 

PMID- 24093592
TI  - Benign extracerebral fluid collection in infancy as a risk factor for the
      development of de novo intracranial arachnoid cysts.
AB  - OBJECT: Intracranial arachnoid cysts are a relatively common benign intracranial
      pathology, accounting for as many as 0.75%-1% of nontraumatic CNS lesions.
      Although it has already been demonstrated that rupture of arachnoid cysts may
      lead to subdural hematomas/hygromas, no study to date has investigated benign
      extracerebral collection in infancy as a possible predisposing factor for further
      development of arachnoid cysts. METHODS: The authors performed a retrospective
      imaging and chart review of macrocephalic infants 12 months old or younger who
      were referred to neurosurgical care at OSF St. Francis Medical Center from 2003
      to 2010, and who were diagnosed with benign extracerebral fluid collection in
      infancy on thin-slice (1-mm) head CT scans. Special attention was given to the
      investigation of risk factors for further development of de novo arachnoid cysts.
      Several epidemiological factors in the infants and mothers were analyzed,
      including gestational age at delivery, mode of delivery, mother's age at
      delivery, delivery complications, birth weight, age of macrocephaly development,
      degree of macrocephaly, family history of macrocephaly, prenatal and postnatal
      history of infection, fontanel status, presence of papilledema, previous history
      of head trauma, and smoking status. Imaging characteristics of the initial scans,
      such as location of subdural collection (frontal vs frontoparietal and
      frontotemporal) and presence of ventriculomegaly, were also evaluated. For those
      patients in whom arachnoid cysts were identified on subsequent CT scans, the size
      and location of the cysts were also analyzed. RESULTS: The authors identified 44
      children with benign extracerebral fluid collection in infancy. From this group,
      over a mean follow-up of 13 months (range 6-13 months), 18 children developed
      intracranial arachnoid cysts (a 40.9% incidence of de novo development of
      arachnoid cysts), with 27.8% presenting with bilateral cysts. In the multiple
      logistic regression analysis, infants who presented with an extracerebral
      collection restricted to the bilateral frontal region were more likely to develop
      intracranial arachnoid cysts (p = 0.035) than those with collections involving
      the frontotemporal and frontoparietal regions (odds ratio [OR] = 5.73).
      Additionally, children with benign extracerebral fluid collections and
      plagiocephaly were more likely to develop intracranial arachnoid cysts (p =
      0.043) than those without plagiocephaly (OR = 4.96). CONCLUSIONS: This is the
      first report in the neurosurgical literature demonstrating that benign
      extracerebral fluid collections in infancy may constitute a significant risk
      factor for development of de novo arachnoid cysts. These findings support a 2-hit
      hypothesis for the development of arachnoid cysts, in which the combination of an
      embryological defect in arachnoid development followed by a second event leading
      to impairment of CSF fluid absorption in early childhood could lead to abnormal
      CSF dynamics and the consequent expansion of fluid collections in the
      intraarachnoid spaces.

PMID- 24093593
TI  - Metameric syndromes.

PMID- 24093594
TI  - Transformation of the matrix structure of shrimp shells during bacterial
      deproteination and demineralization.
AB  - BACKGROUND: After cellulose and starch, chitin is the third-most abundant
      biopolymer on earth. Chitin or its deacetylated derivative chitosan is a valuable
      product with a number of applications. It is one of the main components of shrimp
      shells, a waste product of the fish industry. To obtain chitin from Penaeus
      monodon, wet and dried shrimp shells were deproteinated with two specifically
      enriched proteolytic cultures M1 and M2 and decalcified by in-situ lactic acid
      forming microorganisms. The viscosity of biologically processed chitin was
      compared with chemically processed chitin. The former was further investigated
      for purity, structure and elemental composition by several microscopic techniques
      and (13)C solid state NMR spectroscopy. RESULTS: About 95% of the protein of wet
      shrimp shells was removed by proteolytic enrichment culture M2 in 68 h.
      Subsequent decalcification by lactic acid bacteria (LAB) took 48 h.
      Deproteination of the same amount of dried shrimps that contained a 3 * higher
      solid content by the same culture was a little bit faster and was finished after
      140 h. The viscosity of chitin was in the order of chemically processed chitin >
      bioprocessed chitin > commercially available chitin. Results revealed changes in
      fine structure and chemical composition of the epi-, exo- and endocuticle of
      chitin from shrimp shells during microbial deproteination and demineralization.
      From transmission electron microscopy (TEM) overlays and electron energy loss
      spectroscopy (EELS) analysis, it was found that most protein was present in the
      exocuticle, whereas most chitin was present in the endocuticle. The calcium
      content was higher in the endocuticle than in the exocuticle.13C solid state NMR
      spectra of different chitin confirmed < 3% impurities in the final product.
      CONCLUSIONS: Bioprocessing of shrimp shell waste resulted in a chitin with high
      purity. Its viscosity was higher than that of commercially available chitin but
      lower than that of chemically prepared chitin in our lab. Nevertheless, the
      biologically processed chitin is a promising alternative for less viscous
      commercially available chitin. Highly viscous chitin could be generated by our
      chemical method. Comprehensive structural analyses revealed the distribution of
      the protein and Ca matrix within the shrimp shell cuticle which might be helpful
      in developing shrimp waste processing techniques.

PMID- 24093595
TI  - A sampling framework for incorporating quantitative mass spectrometry data in
      protein interaction analysis.
AB  - BACKGROUND: Comprehensive protein-protein interaction (PPI) maps are a powerful
      resource for uncovering the molecular basis of genetic interactions and providing
      mechanistic insights. Over the past decade, high-throughput experimental
      techniques have been developed to generate PPI maps at proteome scale, first
      using yeast two-hybrid approaches and more recently via affinity purification
      combined with mass spectrometry (AP-MS). Unfortunately, data from both protocols
      are prone to both high false positive and false negative rates. To address these
      issues, many methods have been developed to post-process raw PPI data. However,
      with few exceptions, these methods only analyze binary experimental data (in
      which each potential interaction tested is deemed either observed or unobserved),
      neglecting quantitative information available from AP-MS such as spectral counts.
      RESULTS: We propose a novel method for incorporating quantitative information
      from AP-MS data into existing PPI inference methods that analyze binary
      interaction data. Our approach introduces a probabilistic framework that models
      the statistical noise inherent in observations of co-purifications. Using a
      sampling-based approach, we model the uncertainty of interactions with low
      spectral counts by generating an ensemble of possible alternative experimental
      outcomes. We then apply the existing method of choice to each alternative outcome
      and aggregate results over the ensemble. We validate our approach on three recent
      AP-MS data sets and demonstrate performance comparable to or better than state-of
      the-art methods. Additionally, we provide an in-depth discussion comparing the
      theoretical bases of existing approaches and identify common aspects that may be
      key to their performance. CONCLUSIONS: Our sampling framework extends the
      existing body of work on PPI analysis using binary interaction data to apply to
      the richer quantitative data now commonly available through AP-MS assays. This
      framework is quite general, and many enhancements are likely possible. Fruitful
      future directions may include investigating more sophisticated schemes for
      converting spectral counts to probabilities and applying the framework to direct
      protein complex prediction methods.

PMID- 24093596
TI  - Progressive resistance training for community-dwelling women aged 90 or older; a
      single-subject experimental design.
AB  - PURPOSE: To examine the effect and feasibility of a 12-week programme of
      progressive resistance exercise on a group of nonagenarian (>=90 years) community
      dwelling women. METHOD: An A-B single-subject experimental design was applied.
      Visual analyses were used for estimating the effect of the intervention. Outcome
      measurements were: Timed Up and Go (TUG), comfortable walking speed and 30-s
      chair stands. The programme comprised four exercises, following the principle of
      overload, aiming at improving strength in the main muscle groups. Feasibility of
      the progressive resistance intervention was assessed by recording the recruitment
      of participants, adherence to the intervention and adverse events. RESULTS:
      Twenty-seven women were invited; eight women aged 90 and above agreed to
      participate and six completed the study. They suffered from one to 10 chronic
      medical conditions. All improved their performance in the TUG test. Five of the
      six participants achieved a higher walking speed (11-59%) and four of them
      improved on the 30-s chair-stand test with five to 10 stands. No major adverse
      events were reported. CONCLUSION: Progressive resistance training was a safe and
      efficient method to enhance mobility and increase lower body strength in this
      heterogeneous group of nonagenarian community-dwelling women. IMPLICATIONS FOR
      REHABILITATION: Progressive resistance (PRT) training was found to be a safe and
      efficient method to enhance mobility and increase lower body strength in a group
      of community-dwelling women 90+. Participants with the poorest initial functional
      performance had great benefits, and the improvements appeared already after a few
      weeks of PRT. PRT might be useful in the rehabilitation field and could be
      implemented in facilities such as day care and senior centres frequented by very
      old persons with mobility limitations.

PMID- 24093597
TI  - Factors associated with stair climbing ability in patients with knee
      osteoarthritis and knee arthroplasty: a systematic review.
AB  - PURPOSE: People with knee osteoarthritis (OA) report ongoing limitations in
      climbing stairs, even after total knee arthroplasty (TKA). The aim of this
      systematic review was to synthesise the available evidence of factors affecting
      stair climbing ability in patients with knee OA before and after TKA. METHOD: A
      systematic search was conducted of common electronic databases. All English
      language abstracts where stair-climbing was assessed in patients with either knee
      OA or at least 6 months after TKA, and a relationship to any physical,
      psychological or demographic factors was reported. RESULTS: Thirteen studies were
      included in the final review, nine investigated a knee OA population, and four
      investigated a TKA population. For patients with knee OA there was consistent and
      convincing evidence that greater stair-climbing ability was related to stronger
      lower limb muscles and less knee pain. For patients with TKA there was much less
      research, and no conclusions could be reached. CONCLUSIONS: For people with knee
      OA there is evidence that some physical, demographic and psychosocial factors are
      related to stair-climbing ability. However, the evidence for similar
      relationships in the TKA population is scarce and needs more extensive research.
      Implications for Rehabilitation People with knee osteoarthritis experience
      difficulty when climbing stairs, and this remains challenging even after knee
      replacement. For people with knee osteoarthritis, a range of physical,
      demographic and psychosocial factors contribute to stair-climbing ability,
      however, evidence for similar relationships in the TKA population is scarce.
      Rehabilitation that is multi-faceted may be the best approach to improve stair
      climbing in people with knee osteoarthritis.

PMID- 24093598
TI  - Identification of mildew resistance in wild and cultivated Central Asian grape
      germplasm.
AB  - BACKGROUND: Cultivated grapevines, Vitis vinifera subsp. sativa, evolved from
      their wild relative, V. vinifera subsp. sylvestris. They were domesticated in
      Central Asia in the absence of the powdery mildew fungus, Erysiphe necator, which
      is thought to have originated in North America. However, powdery mildew
      resistance has previously been discovered in two Central Asian cultivars and in
      Chinese Vitis species. RESULTS: A set of 380 unique genotypes were evaluated with
      data generated from 34 simple sequence repeat (SSR) markers. The set included 306
      V. vinifera cultivars, 40 accessions of V. vinifera subsp. sylvestris, and 34
      accessions of Vitis species from northern Pakistan, Afghanistan and China. Based
      on the presence of four SSR alleles previously identified as linked to the
      powdery mildew resistance locus, Ren1, 10 new mildew resistant genotypes were
      identified in the test set: eight were V. vinifera cultivars and two were V.
      vinifera subsp. sylvestris based on flower and seed morphology. Sequence
      comparison of a 620 bp region that includes the Ren1-linked allele (143 bp) of
      the co-segregating SSR marker SC8-0071-014, revealed that the ten newly
      identified genotypes have sequences that are essentially identical to the
      previously identified mildew resistant V. vinifera cultivars: 'Kishmish vatkana'
      and 'Karadzhandal'. Kinship analysis determined that three of the newly
      identified powdery mildew resistant accessions had a relationship with 'Kishmish
      vatkana' and 'Karadzhandal', and that six were not related to any other accession
      in this study set. Clustering procedures assigned accessions into three groups:
      1) Chinese species; 2) a mixed group of cultivated and wild V. vinifera; and 3)
      table grape cultivars, including nine of the powdery mildew resistant accessions.
      Gene flow was detected among the groups. CONCLUSIONS: This study provides
      evidence that powdery mildew resistance is present in V. vinifera subsp.
      sylvestris, the dioecious wild progenitor of the cultivated grape. Four first
      degree parent progeny relationships were discovered among the hermaphroditic
      powdery mildew resistant cultivars, supporting the existence of intentional grape
      breeding efforts. Although several Chinese grape species are resistant to powdery
      mildew, no direct genetic link to the resistance found in V. vinifera could be
      established.

PMID- 24093600
TI  - Bloodstream infection as a predictor for mortality in severe burn patients: an 11
      year study.
AB  - In this study we collected and analysed data of the severe burn patients at our
      institution over an 11-year period in order to shed light on the controversial
      role of bloodstream infection (BSI) as a predictive factor for mortality in this
      burn population. The factors examined were age, total body surface area, smoke
      inhalation, presence of BSI, and BSI with resistant bacteria. In total 1081 burn
      patients were hospitalized from 2001 to 2011, of whom 4% died. We focused here on
      158 severe burn patients, 74 of whom developed BSI, and 35 who died. Using
      univariate analysis, it appeared that the BSI group had a threefold greater
      chance of mortality compared to the non-BSI group. Patients with a Ryan score 3
      had a 100% chance of mortality and those with a score 0 had 0%. Thus, focusing
      only on Ryan score 1 and score 2 patients, BSI did not contribute to mortality,
      nor was it shown to contribute to mortality in a multivariate analysis in which
      the score and BSI were included together. When BSI did occur, it predicted longer
      hospitalization periods. We conclude that BSI predicts longer length of
      hospitalization stay but does not contribute to the prediction of mortality
      beyond that offered by the Ryan score in a severe burn population.

PMID- 24093599
TI  - Statin exposure is associated with decreased asthma-related emergency department
      visits and oral corticosteroid use.
AB  - RATIONALE: Statins, or HMG-CoA reductase inhibitors, may aid in the treatment of
      asthma through their pleiotropic antiinflammatory effects. OBJECTIVES: To examine
      the effect of statin therapy on asthma-related exacerbations using a large
      population-based cohort. METHODS: Statin users aged 31 years or greater with
      asthma were identified from the Population-Based Effectiveness in Asthma and Lung
      population, which includes data from five health plans. Statin exposure and
      asthma exacerbations were assessed over a 24-month observation period. Statin
      users with a statin medication possession ratio greater than or equal to 80% were
      matched to non-statin users by age, baseline asthma therapy, site of enrollment,
      season at baseline, and propensity score, which was calculated based on patient
      demographics and Deyo-Charlson conditions. Asthma exacerbations were defined as
      two or more oral corticosteroid dispensings, asthma-related emergency department
      visits, or asthma-related hospitalizations. The association between statin
      exposure and each of the three outcome measures was assessed using conditional
      logistic regression. MEASUREMENTS AND MAIN RESULTS: Of the 14,566 statin users,
      8,349 statin users were matched to a nonuser. After adjusting for Deyo-Charlson
      conditions that remained unbalanced after matching, among statin users, statin
      exposure was associated with decreased odds of having asthma-related emergency
      department visits (odds ratio [OR], 0.64; 95% confidence interval [CI], 0.53
      0.77; P < 0.0001) and two or more oral corticosteroid dispensings (OR, 0.90; 95%
      CI, 0.81-0.99; P = 0.04). There were no differences in asthma-related
      hospitalizations (OR, 0.91; 95% CI, 0.66-1.24; P = 0.52). CONCLUSIONS: Among
      statin users with asthma, statin exposure was associated with decreased odds of
      asthma-related emergency department visits and oral corticosteroid dispensings.

PMID- 24093601
TI  - A molecular genetic study of autism and related phenotypes in extended pedigrees.
AB  - BACKGROUND: Efforts to uncover the risk genotypes associated with the familial
      nature of autism spectrum disorder (ASD) have had limited success. The study of
      extended pedigrees, incorporating additional ASD-related phenotypes into linkage
      analysis, offers an alternative approach to the search for inherited ASD
      susceptibility variants that complements traditional methods used to study the
      genetics of ASD. METHODS: We examined evidence for linkage in 19 extended
      pedigrees ascertained through ASD cases spread across at least two (and in most
      cases three) nuclear families. Both compound phenotypes (i.e., ASD and, in non
      ASD individuals, the broad autism phenotype) and more narrowly defined components
      of these phenotypes, e.g., social and repetitive behavior, pragmatic language,
      and anxiety, were examined. The overarching goal was to maximize the aggregate
      information available on the maximum number of individuals and to disaggregate
      syndromic phenotypes in order to examine the genetic underpinnings of more
      narrowly defined aspects of ASD behavior. RESULTS: Results reveal substantial
      between-family locus heterogeneity and support the importance of previously
      reported ASD loci in inherited, familial, forms of ASD. Additional loci, not seen
      in the ASD analyses, show evidence for linkage to the broad autism phenotype
      (BAP). BAP peaks are well supported by multiple subphenotypes (including anxiety,
      pragmatic language, and social behavior) showing linkage to regions overlapping
      with the compound BAP phenotype. Whereas 'repetitive behavior', showing the
      strongest evidence for linkage (Posterior Probability of Linkage = 62% at 6p25.2
      24.3, and 69% at 19p13.3), appears to be linked to novel regions not detected
      with other compound or narrow phenotypes examined in this study. CONCLUSIONS:
      These results provide support for the presence of key features underlying the
      complexity of the genetic architecture of ASD: substantial between-family locus
      heterogeneity, that the BAP appears to correspond to sets of subclinical features
      segregating with ASD within pedigrees, and that different features of the ASD
      phenotype segregate independently of one another. These findings support the
      additional study of larger, even more individually informative pedigrees,
      together with measurement of multiple, behavioral- and biomarker-based
      phenotypes, in both affected and non-affected individuals, to elucidate the
      complex genetics of familial ASD.

PMID- 24093602
TI  - Preliminary results in quantitation of HLA-DRA by real-time PCR: a promising
      approach to identify immunosuppression in sepsis.
AB  - INTRODUCTION: Reduced monocyte human leukocyte antigen (mHLA)-DR surface
      expression in the late phase of sepsis is postulated as a general biomarker of
      sepsis-induced immunosuppression and an independent predictor of nosocomial
      infections. METHODS: Fifty-nine patients with sepsis and blood culture growing
      pathogenic bacteria were studied. Blood samples were collected at day 1 or 2
      after admission, for measurement of mHLA-DR by flow cytometry and mRNA expression
      of HLA-DRA and class II transactivator (CIITA) by qRT-PCR. Blood samples from
      blood donors were used as controls (n = 30). RESULTS: A significant reduced
      expression of mHLA-DR, HLA-DRA, and CIITA was seen in septic patients compared
      with controls. HLA-DRA mRNA level in whole blood was highly correlated with
      surface expression of mHLA-DR. CONCLUSIONS: Patients with sepsis display a
      diminished expression of HLA-DR at the monocyte surface as well as in the gene
      expression at the mRNA level. The mRNA expression level of HLA-DRA monitored by
      qRT-PCR correlates highly with surface expression of HLA-DR and appears to be a
      possible future biomarker for evaluation of immunosuppression in sepsis.

PMID- 24093603
TI  - Cu(II)-catalyzed allylic silylation of Morita-Baylis-Hillman alcohols via dual
      activation of Si-B bond and hydroxyl group.
AB  - The reaction of Morita-Baylis-Hillman (MBH) alcohols with Me2PhSiBpin under the
      catalysis of Cu(OTf)2/pyridine in methanol has been developed. The direct
      silylation of allylic alcohols via dual activation of the Si-B bond and the
      hydroxyl group of the MBH alcohol provides an efficient and convenient method for
      the synthesis of functionalized allylsilanes. 

PMID- 24093604
TI  - Selective Co/Ti cooperatively catalyzed biaryl couplings of aryl halides with
      aryl metal reagents.
AB  - Various aryl bromides or chlorides, including those bearing a free COOH, OH,
      CONHR, and SO2NHR group, coupled with aryl magnesium or lithium reagents in the
      presence of 7.5 mol % CoCl2/15 mol % PBu3 and substoichiometric Ti(OEt)4 (40 mol
      % to ArM) at room temperature in high yields with high chemo- and
      regioslectivity. This simple reaction represents the first example of Co/Ti
      cooperative catalysis which plays a key role in suppressing undesired
      homocouplings. 

PMID- 24093605
TI  - The use of chitosan-based scaffolds to enhance regeneration in the nervous
      system.
AB  - Various biomaterials have been proposed to build up scaffolds for promoting
      neural repair. Among them, chitosan, a derivative of chitin, has been raising
      more and more interest among basic and clinical scientists. A number of studies
      with neuronal and glial cell cultures have shown that this biomaterial has
      biomimetic properties, which make it a good candidate for developing innovative
      devices for neural repair. Yet, in vivo experimental studies have shown that
      chitosan can be successfully used to create scaffolds that promote regeneration
      both in the central and in the peripheral nervous system. In this review, the
      relevant literature on the use of chitosan in the nervous tissue, either alone or
      in combination with other components, is overviewed. Altogether, the promising in
      vitro and in vivo experimental results make it possible to foresee that time for
      clinical trials with chitosan-based nerve regeneration-promoting devices is
      approaching quickly. 

PMID- 24093606
TI  - Interfaces with the peripheral nerve for the control of neuroprostheses.
AB  - Nervous system injuries lead to loss of control of sensory, motor, and autonomic
      functions of the affected areas of the body. Provided the high amount of people
      worldwide suffering from these injuries and the impact on their everyday life,
      numerous and different neuroprostheses and hybrid bionic systems have been
      developed to restore or partially mimic the lost functions. A key point for
      usable neuroprostheses is the electrode that interfaces the nervous system and
      translates not only motor orders into electrical outputs that activate the
      prosthesis but is also able to transform sensory information detected by the
      machine into signals that are transmitted to the central nervous system. Nerve
      electrodes have been classified with regard to their invasiveness in extraneural,
      intraneural, and regenerative. The more invasive is the implant the more
      selectivity of interfacing can be reached. However, boosting invasiveness and
      selectivity may also heighten nerve damage. This chapter provides a general
      overview of nerve electrodes as well as the state-of-the-art of their biomedical
      applications in neuroprosthetic systems. 

PMID- 24093607
TI  - The use of shock waves in peripheral nerve regeneration: new perspectives?
AB  - Low-energy extracorporeal shock wave treatment (ESWT) is a relatively new
      therapeutic tool that is widely used for the treatment of epicondylitis and
      plantar fasciitis and to foster bone and wound healing. Shock waves, sonic pulses
      with high energy impact, are thought to induce biochemical changes within the
      targeted tissues through mechanotransduction. The biological effects of ESWT are
      manifested in improved vascularization, the local release of growth factors, and
      local anti-inflammatory effects, but the target cells too are influenced. ESWT
      appears to have differential effects on peripheral nerves and has been proved to
      promote axonal regeneration after axotomy. This review discusses the effects of
      ESWT on intact and injured peripheral nerves and suggests a multiple mechanism of
      action. 

PMID- 24093608
TI  - Phototherapy and nerve injury: focus on muscle response.
AB  - Preservation of biochemical processes in muscles is a major challenge in patients
      with severe peripheral nerve injury. In this chapter, we address the effects of
      laser irradiation and biochemical transformation in muscle, using in vitro and in
      vivo experimental models. The authors attempt to explain the possible mechanism
      of laser phototherapy applied on skeletal muscle on the basis of literature
      review and new results. A detailed knowledge of the evolution of endplates
      acetylcholine receptors and creatine kinase activity following laser irradiation
      can help to understand the therapeutic effect of laser phototherapy on muscle.
      This study showed that the laser phototherapy increases biochemical activity in
      intact muscle and thus could have direct therapeutic applications on muscle,
      especially during progressive atrophy resulting from peripheral nerve injury. 

PMID- 24093609
TI  - Electrical stimulation for promoting peripheral nerve regeneration.
AB  - The peripheral nervous system has the intrinsic capacity to regenerate axons into
      target tissues, and peripheral nerves severely damaged or transected can be
      reconstructed by microsurgical techniques. The aim of peripheral nerve surgery is
      to pave way for fast and most possible thorough functional recovery. However,
      full functional recovery is rarely seen and several reasons for this have already
      been discovered. Based on these discoveries, therapeutic strategies supplementary
      to nerve microsurgery have been conceived with electrical stimulation of the
      denervated muscles or the proximal nerve stump or reconstructed area itself being
      among them. This chapter shortly describes the commonly accepted reasons for
      incomplete functional recovery and reviews the effects of varying electrical
      stimulation paradigms on the essentials for axonal regeneration and functional
      target reinnervation. We conclude the chapter with promising examples where
      electrical stimulation did already demonstrate to accelerate and increase
      functional recovery in the clinic. 

PMID- 24093610
TI  - Role of physical exercise for improving posttraumatic nerve regeneration.
AB  - Despite the great regenerative ability of the peripheral nervous system (PNS),
      traumatic peripheral nerve damage often causes severe chronic disability.
      Rehabilitation following PNS trauma usually employs therapeutic exercise in an
      attempt to reanimate the target organs and stimulate functional recovery. Over
      the past years, important neurobiological determinants of PNS regeneration and
      successful end-organ reinnervation were unveiled. Such knowledge provides cues
      for designing novel strategies for treating and rehabilitating traumatic PNS
      damage. Physical exercise, by means of treadmill or wheel running, is
      neuroprotective and neuroregenerative. Research conducted on rodents demonstrates
      that endurance exercise modulates several of the cellular and molecular responses
      to peripheral nerve injury and by doing so it stimulates nerve regeneration and
      functional recovery following experimental PNS injury. Treadmill running
      increases the number of regenerating neurons, the rate of axonal growth, and the
      extent of muscle reinnervation following peripheral nerve injury. Furthermore,
      treadmill running has the ability to increase the release of neurotrophins and
      growth factors in the spinal cord, the injured nerve, and reinnervating muscles.
      Treadmill running also seems to prevent the development of neuropathic pain and
      allodynia as a result of peripheral nerve damage. In addition, physical exercise,
      even if performed for a short period of time, exerts positive conditioning
      effects in neuroregeneration capacity, improving the acute response to peripheral
      nerve insults. Some of these effects can also be obtained with passive exercise
      or manual stimulation. In humans, however, evidence demonstrating a positive
      effect of exercise on nerve regeneration is at best poor. 

PMID- 24093611
TI  - The role of timing in nerve reconstruction.
AB  - The surgeon, who treats nerve injuries, should have knowledge about how
      peripheral nerves react to trauma, particularly an understanding about the
      extensive pathophysiological alterations that occur both in the peripheral and in
      the central nervous system. A large number of factors influence the functional
      outcome, where the surgeon only can affect a few of them. In view of the new
      knowledge about the delicate intracellular signaling pathways that are rapidly
      initiated in neurons and in nonneuronal cells with the purpose to induce nerve
      regeneration, the timing of nerve repair and reconstruction after injury has
      gained more interest. It is crucial to understand and to utilize the inborn
      mechanisms for survival and regeneration of neurons and for activation, survival,
      and proliferation of the Schwann cells and other cells that are acting after a
      nerve injury. Thus, experimental and clinical data clearly point toward the
      advantage of early nerve repair and reconstruction of injuries. Following an
      appropriate diagnosis of a nerve injury, the nerve should be promptly repaired or
      reconstructed, and new rehabilitation strategies should early be initiated.
      Considering nerve transfers in the treatment arsenal can shorten the time of
      nerve reinnervation of muscle targets. Timing of nerve repair and reconstruction
      is crucial after nerve injury. 

PMID- 24093612
TI  - Future perspectives in nerve repair and regeneration.
AB  - After peripheral nerve injuries, the process of nerve regeneration and target
      reinnervation is very complex and depends on many different events occurring not
      only at the lesion site but also proximally and distally to it. In spite of the
      recent scientific and technological advancements, the need to find out new
      strategies to improve clinical nerve repair and regeneration remains. To reach
      this goal, the therapeutic strategy should thus exert its effects at different
      levels in order to simultaneously potentiate axonal regeneration, increase
      neuronal survival, modulate central reorganization, and inhibit or reduce target
      organ atrophy. It is expected that this multilevel approach might lead to
      significant improvement in the functional outcome and thus the quality of life of
      the patients suffering from peripheral nerve injury. 

PMID- 24093613
TI  - Peripheral nerve repair is no longer a matter of surgical reconstruction only.

PMID- 24093614
TI  - Time-in-a-bottle (TIAB): a longitudinal, correlational study of patterns,
      potential predictors, and outcomes of immunosuppressive medication adherence in
      adult kidney transplant recipients.
AB  - This study examined patterns, potential predictors, and outcomes of
      immunosuppressive medication adherence in a convenience sample of 121 kidney
      transplant recipients aged 21 yr or older from three kidney transplant centers
      using a theory-based, descriptive, correlational, longitudinal design. Electronic
      monitoring was conducted for 12 months using electronic monitoring. Participants
      were persistent in taking their immunosuppressive medications, but execution,
      which includes both taking and timing, was poor. Older age was the only
      demographic variable associated with medication adherence (r = 0.25; p = 0.005).
      Of the potential predictors examined, only medication self-efficacy was
      associated with medication non-adherence, explaining about 9% of the variance (r
      = 0.31, p = 0.0006). The few poor outcomes that occurred were not significantly
      associated with medication non-adherence, although the small number of poor
      outcomes may have limited our ability to detect a link. Future research should
      test fully powered, theory-based, experimental interventions that include a
      medication self-efficacy component.

PMID- 24093615
TI  - Antiviral treatment for hepatitis B virus recurrence following liver
      transplantation.
AB  - The purpose of this study was to identify the factors associated with the
      recurrence of hepatitis B virus (HBV) following liver transplantation (LT) for
      HBV-related disease and to recognize the outcome of treatment for HBV recurrence
      with oral nucleos(t)ide analogues. Six hundred and sixty-seven LTs were performed
      for HBsAg-positive adult patients in our institute from 1996 to 2010. HBV
      prophylaxis was performed by hepatitis B immunoglobulin (HBIG) monotherapy or
      HBIG and entecavir combination therapy. There were 63 cases (11.4%) of HBV
      recurrences during a median follow-up of 51 months. The median time to HBV
      recurrence was 22 months. A preoperative HBV DNA load of more than 10(5) IU/mL,
      HBIG monotherapy, and hepatocellular carcinoma in the explant liver were
      independent risk factors for HBV recurrence following LT in multivariate
      analysis. Patient survival at 10 yr was 54.2% for HBV-recurrent patients. Among
      patients with HBV recurrence, HBsAg seroclearance was achieved in 13 patients
      (20.6%), but HBsAg seroclearance did not affect survival in these patients after
      the recurrence of HBV (p = 0.28). The recurrence of HBV led to graft failure in
      six cases. HBV recurrence should be prevented by strict management of pre
      transplant HBV viremia and an effective post-transplant HBV prophylaxis.

PMID- 24093616
TI  - Secretory expression of biologically active human Herpes virus interleukin-10
      analogues in Escherichia coli via a modified Sec-dependent transporter construct.
AB  - BACKGROUND: Interleukin-10 homologues encoded by Herpes viruses such as Epstein
      Barr virus (EBV) and human cytomegalovirus (HCMV) hold interesting structural and
      biological characteristics compared to human interleukin-10 (hIL-10) that render
      these proteins promising candidates for therapeutic application in inflammatory
      bowel disease (IBD). Intestinal delivery of cytokines using bacterial carriers as
      chassis represents a novel approach for treatment of IBD patients. For proof of
      concept, a Sec-dependent transporter construct was designed for secretory
      expression of recombinant viral IL-10 proteins in the periplasm of Escherichia
      coli laboratory strain BL21 (DE3), which might serve as part of a prospective
      lysis based delivery and containment system. RESULTS: The signal peptide of E.
      coli outer membrane protein F fused to the mature form of the viral IL-10
      proteins enabled successful transport into the periplasm, a compartment which
      seems crucial for proper assembly of the dimeric configuration of the cytokines.
      Cytokine concentrations in different bacterial compartments were determined by
      ELISA and achieved yields of 67.8 ng/ml +/- 24.9 ng/ml for HCMV IL-10 and 1.5
      MUg/ml +/- 841.4 ng/ml for EBV IL-10 in the periplasm. Immunoblot analysis was
      used to confirm the correct size of the E. coli-derived recombinant cytokines.
      Phosphorylation of signal transducer and activator of transcription 3 (STAT3) as
      part of the signal transduction cascade after IL-10 receptor interaction, as well
      as suppression of tumor necrosis factor alpha (TNF-alpha) release of
      lipopolysaccharide-stimulated mouse macrophages were used as read-out assays for
      proving in vitro biological activity of the E. coli derived, recombinant viral IL
      10 counterparts. CONCLUSIONS: In this study, proof of principle is provided that
      E. coli cells are a suitable chassis for secretory expression of viral IL-10
      cytokines encoded by codon-optimized synthetic genes fused to the E. coli ompF
      signal sequence. In vitro biological activity evidenced by activation of
      transcription factor STAT3 and suppression of TNF-alpha in mammalian cell lines
      was shown to be strictly dependent on export of viral IL-10 proteins into the
      periplasmic compartment. E. coli might serve as carrier system for in situ
      delivery of therapeutic molecules in the gut, thus representing a further step in
      the development of novel approaches for treatment of IBD.

PMID- 24093617
TI  - A boy with a tight skin: Borrelia-associated early-onset morphea.
AB  - We present a case of a 16-year-old boy with morphea caused by Borrelia
      burgdorferi. We re-emphasise an immunohistochemical method, focus floating
      microscopy (FFM), to detect Borrelia burgdorferi spirochetes in tissue sections.
      Focus floating microscopy (FFM) proved to be more sensitive than polymerase chain
      reaction (PCR) and nearly equally specific. 

PMID- 24093618
TI  - Nitric oxide inhibition of alcohol dehydrogenase in fresh-cut apples ( Malus
      domestica Borkh).
AB  - The effects of nitric oxide (NO) and nitrite treatment on alcohol dehydrogenase
      activity and the shelf life of apple tissue were investigated. Fresh-cut apple
      slices were stored for 2 days at 6  degrees C in 0.25-1% NO (v/v, balance N2) or
      100% N2 atmospheres. Slices were also treated with 1% NO or 2 mM sodium nitrite
      (NaNO2) for 20 min, stored for 6 weeks in 100% N2 at 6  degrees C, and analyzed
      for acetaldehyde, ethanol, and ethyl acetate accumulation, firmness, and color.
      Compared with N2 or deionized water controls, treatment with 1% NO or 2 mM NaNO2
      inhibited ethanol accumulation, whereas that of acetaldehyde increased. Ethyl
      acetate accumulation was inhibited only by NO. Slice firmness was not affected by
      NO or NaNO2 treatment, but slices were darker than the untreated controls. NO and
      nitrite may extend the shelf life of fresh-cut produce with low concentrations of
      phenolic compounds. 

PMID- 24093619
TI  - The time has come to radically rethink assisted reproduction.

PMID- 24093621
TI  - Individual boron nanowire has ultra-high specific Young's modulus and fracture
      strength as revealed by in situ transmission electron microscopy.
AB  - Boron nanowires (BNWs) may have potential applications as reinforcing materials
      because B fibers are widely known for their excellent mechanical performance.
      However until now, there have been only few reports on the mechanical properties
      of individual BNW, and in situ transmission electron microscopy (TEM)
      investigations shining a light on their fracture mechanism have not been
      performed. In this paper, we applied in situ high-resolution TEM (HRTEM)
      technique to study the mechanical properties of individual BNWs using three
      loading schemes. The mean fracture strength and the maximum strain of individual
      BNWs were measured to be 10.4 GPa and 4.1%, respectively, during the tensile
      tests. And the averaged Young's modulus was calculated to be 308.2 GPa under
      tensile and compression tests. Bending experiments for the first time performed
      on individual BNWs revealed that their maximum bending strain could reach 9.9%
      and their ultimate bending stress arrived at 36.2 GPa. These figures are much
      higher than those of Si and ZnO nanowires known for their high bending strength.
      Moreover, the BNWs exhibited very high specific fracture strength (3.9
      (GPa.cm(3))/g) and specific elastic modulus (130.6 (GPa.cm(3))/g), which are
      several dozens of times larger compared to many nanostructures known for their
      superb mechanical behaviors. At last, the effect of surface oxide layer on the
      Young's modulus, fracture strength and maximum bending strength of individual
      BNWs was elucidated to extract their intrinsic mechanical parameters using
      calculated corrections. All experimental results suggest that the present BNW are
      a bright promise as lightweight reinforcing fillers. 

PMID- 24093622
TI  - Biobehavior in normal and tumor-bearing mice of tobacco mosaic virus.
AB  - Viral nanoparticles (VNPs) have shown great potential as platforms for biomedical
      applications. Before using VNPs for further biomedical applications, it is
      important to clarify their biological behavior in vivo, which is rare for rod
      like VNPs. In this paper, a study of tobacco mosaic virus (TMV), a typical rod
      like VNP, is performed on blood clearance kinetics, biodistributions in both
      normal and tumor-bearing mice, histopathology and cytotoxicity. TMV was
      radiolabeled with (125)I using Iodogen method for in vivo quantitative analysis
      and imaging purpose. In the normal mice, the accumulation of TMV in the immune
      system led to a rapid blood clearance. The uptake of TMVs in the liver was less
      than that in the spleen, which is opposite to the results observed in the case of
      spherical VNPs. No signs of overt toxicity were observed in examined tissues
      according to the results of histological analysis. In addition, similar
      biodistribution patterns were observed in U87MG tumor-bearing mice. 

PMID- 24093623
TI  - Effects of early and intensive neuro-rehabilitative treatment on muscle synergies
      in acute post-stroke patients: a pilot study.
AB  - BACKGROUND: After a stroke, patients show significant modifications of neural
      control of movement, such as abnormal muscle co-activation, and reduced
      selectivity and modulation of muscle activity. Nonetheless, results reported in
      literature do not allow to unequivocally explain whether and, in case, how a
      cerebrovascular accident affects muscle synergies underlying the control of the
      upper limb. These discrepancies suggest that a complete understanding of the
      modular re-organization of muscle activity due to a stroke is still lacking. This
      pilot study aimed at investigating the effects of the conjunction between the
      natural ongoing of the pathology and the intense robot-mediated treatment on
      muscle synergies of the paretic upper limb of subacute post-stroke patients.
      METHODS: Six subacute patients, homogenous with respect to the age and the time
      elapsed from the trauma, and ten healthy age-matched subjects were enrolled. The
      protocol consisted in achieving planar movement of the upper limb while handling
      the end-effector of a robotic platform. Patients underwent 6 weeks long treatment
      while clinical scores, kinematics of the end-effector and muscle activity were
      recorded. Then we verified whether muscle coordination underlying the motor task
      was significantly affected by the cerebrovascular accident and how muscle
      synergies were modified along the treatment. RESULTS: Results show that although
      muscle synergies in subacute stroke patients were qualitatively comparable to
      those of healthy subjects, those underlying the movement of the shoulder can
      reflect the functional deficit induced by the pathology. Moreover, the
      improvement of motor performance due to the treatment was achieved in conjunction
      with slight modifications of muscle synergies. In this regard, modifications of
      muscle synergies appeared to be influenced by the different recovering mechanisms
      across patients presumably due to the heterogeneity of lesions, sides and
      location of the accident. CONCLUSIONS: The results support the hypothesis that
      muscle synergies reflect the injury of the cerebrovascular accident and could
      document the effects of the functional recovery due to a suitable and customized
      treatment. Therefore, they open up new possibilities for the development of more
      effective neuro-rehabilitation protocols.

PMID- 24093624
TI  - Listening in on difficult conversations: an observational, multi-center
      investigation of real-time conversations in medical oncology.
AB  - BACKGROUND: The quality of communication in medical care has been shown to
      influence health outcomes. Cancer patients, a highly diverse population,
      communicate with their clinical care team in diverse ways over the course of
      their care trajectory. Whether that communication happens and how effective it is
      may relate to a variety of factors including the type of cancer and the patient's
      position on the cancer care continuum. Yet, many of the routine needs of cancer
      patients after initial cancer treatment are often not addressed adequately. Our
      goal is to identify areas of strength and areas for improvement in cancer
      communication by investigating real-time cancer consultations in a cross section
      of patient-clinician interactions at diverse study sites. METHODS/DESIGN: In this
      paper we describe the rationale and approach for an ongoing observational study
      involving three institutions that will utilize quantitative and qualitative
      methods and employ a short-term longitudinal, prospective follow-up component to
      investigate decision-making, key topics, and clinician-patient-companion
      communication dynamics in clinical oncology. DISCUSSION: Through a comprehensive,
      real-time approach, we hope to provide the fundamental groundwork from which to
      promote improved patient-centered communication in cancer care.

PMID- 24093625
TI  - Therapeutic antibodies as a treatment option for dengue fever.
AB  - Dengue fever is the most prevalent mosquito-borne viral disease globally with
      about 100 million cases of acute dengue annually. Severe dengue infection can
      result in a life-threatening illness. In the absence of either a licensed vaccine
      or antiviral drug against dengue, therapeutic antibodies that neutralize dengue
      virus (DENV) may serve as an effective medical countermeasure against severe
      dengue. However, therapeutic antibodies would need to effectively neutralize all
      four DENV serotypes. It must not induce antibody-dependent enhancement of DENV
      infection in monocytes/macrophages through Fc gamma receptor (FcgammaR)-mediated
      phagocytosis, which is hypothesized to increase the risk of severe dengue. Here,
      we review the strategies and technologies that can be adopted to develop
      antibodies for therapeutic applications. We also discuss the mechanism of
      antibody neutralization in the cells targeted by DENV that express Fc gamma
      receptor. These studies have provided significant insight toward the use of
      therapeutic antibodies as a potentially promising bulwark against dengue. 

PMID- 24093626
TI  - Ab initio treatment of ion-induced charge transfer dynamics of isolated 2-deoxy-D
      ribose.
AB  - Modeling-induced radiation damage in biological systems, in particular, in DNA
      building blocks, is of major concern in cancer therapy studies. Ion-induced
      charge-transfer dynamics may indeed be involved in proton and hadrontherapy
      treatments. We have thus performed a theoretical approach of the charge-transfer
      dynamics in collision of C(4+) ions and protons with isolated 2-deoxy-D-ribose in
      a wide collision energy range by means of ab initio quantum chemistry molecular
      methods. The comparison of both projectile ions has been performed with regard to
      previous theoretical and experimental results. The charge transfer appears
      markedly less efficient with the 2-deoxy-D-ribose target than that with
      pyrimidine nucleobases, which would induce an enhancement of the fragmentation
      process in agreement with experimental measurements. The mechanism has been
      analyzed with regard to inner orbital excitations, and qualitative tendencies
      have been pointed out for studies on DNA buiding block damage.

PMID- 24093627
TI  - Atypical effective connectivity of social brain networks in individuals with
      autism.
AB  - Failing to engage in joint attention is a strong marker of impaired social
      cognition associated with autism spectrum disorder (ASD). The goal of this study
      was to localize the source of impaired joint attention in individuals with ASD by
      examining both behavioral and fMRI data collected during various tasks involving
      eye gaze, directional cuing, and face processing. The tasks were designed to
      engage three brain networks associated with social cognition [face processing,
      theory of mind (TOM), and action understanding]. The behavioral results indicate
      that even high-functioning individuals with ASD perform less accurately and more
      slowly than neurotypical (NT) controls when processing eyes, but not when
      processing a directional cue (an arrow) that did not involve eyes. Behavioral
      differences between the NT and ASD groups were consistent with differences in the
      effective connectivity of FACE, TOM, and ACTION networks. An independent multiple
      sample greedy equivalence search was used to examine these social brain networks
      and found that whereas NTs produced stable patterns of response across tasks
      designed to engage a given brain network, ASD participants did not. Moreover, ASD
      participants recruited all three networks in a manner highly dissimilar to that
      of NTs. These results extend a growing literature that describes disruptions in
      general brain connectivity in individuals with autism by targeting specific
      networks hypothesized to underlie the social cognitive impairments observed in
      these individuals.

PMID- 24093628
TI  - Antinociceptive activity of Ligusticum porteri preparations and compounds.
AB  - CONTEXT: The roots and rhizomes of Ligusticum porteri Coulter & Rose (Apiaceae)
      are widely used in Mexican folk medicine for several purposes, including painful
      complaints. OBJECTIVE: The main goal of this work was to demonstrate the
      analgesic action in mice of some preparations and major compounds from L.
      porteri. MATERIALS AND METHODS: The extracts, aqueous (AE) and organic (OE), the
      essential oil (EO) and major compounds (10-316 mg/kg) from L. porteri were
      evaluated as potential antinociceptive agents using the acetic acid-induced
      writhing and hot plate tests in ICR mice. RESULTS: All preparations tested
      exhibited significant antinociceptive effect in the two animal pain models
      selected. AE and EO were more effective in the writhing test while OE had a
      better effect in the hot-plate model. On the other hand, Z-ligustilide (1)
      provoked an increment in the latency period to the thermal stimuli in the hot
      plate test at a dose of 31.6 mg/kg, and a decrease in the number of abdominal
      writhes at 10 mg/kg. Z-3-butylidenephthalide (2) induced a dose-dependent
      antinociceptive action in the hot-plate assay; this compound was also effective
      for controlling the pain provoked by chemical irritation at the doses of 10 and
      31.6 mg/kg. Finally, diligustilide (3) inhibited the number of writhing responses
      at all doses tested but was inactive in the hot-plate model. CONCLUSION: The
      present investigation provides in vivo evidence supporting the use of L. porteri
      to treat painful conditions in folk medicine.

PMID- 24093629
TI  - Genetic structure of Plasmodium falciparum populations across the Honduras
      Nicaragua border.
AB  - BACKGROUND: The Caribbean coast of Central America remains an area of malaria
      transmission caused by Plasmodium falciparum despite the fact that morbidity has
      been reduced in recent years. Parasite populations in that region show
      interesting characteristics such as chloroquine susceptibility and low mortality
      rates. Genetic structure and diversity of P. falciparum populations in the
      Honduras-Nicaragua border were analysed in this study. METHODS: Seven neutral
      microsatellite loci were analysed in 110 P. falciparum isolates from endemic
      areas of Honduras (n = 77) and Nicaragua (n = 33), mostly from the border region
      called the Moskitia. Several analyses concerning the genetic diversity, linkage
      disequilibrium, population structure, molecular variance, and haplotype
      clustering were conducted. RESULTS: There was a low level of genetic diversity in
      P. falciparum populations from Honduras and Nicaragua. Expected heterozigosity
      (H(e)) results were similarly low for both populations. A moderate
      differentiation was revealed by the F(ST) index between both populations, and two
      putative clusters were defined through a structure analysis. The main cluster
      grouped most of samples from Honduras and Nicaragua, while the second cluster was
      smaller and included all the samples from the Siuna community in Nicaragua. This
      result could partially explain the stronger linkage disequilibrium (LD) in the
      parasite population from that country. These findings are congruent with the
      decreasing rates of malaria endemicity in Central America.

PMID- 24093631
TI  - Predictors of increased cumulative serum levels of the N-terminal prohormone of
      brain natriuretic peptide 4 days after acute spontaneous subarachnoid hemorrhage.
AB  - OBJECT: The rupture of an intracranial aneurysm is followed by increased
      intracranial pressure and decreased cerebral blood flow. A major systemic stress
      reaction follows, presumably to restore cerebral blood flow. However, this
      reaction can also cause adverse effects, including myocardial abnormalities,
      which are common and can be serious, and increased levels of natriuretic
      peptides, especially brain natriuretic peptide (BNP). The association of BNP with
      fluid and salt balance, vasospasm, brain ischemia, and cardiac injury has been
      studied but almost exclusively regarding events after admission. Brain
      natriuretic peptide has also been measured at various time points and analyzed in
      different ways statistically. The authors approached BNP measurement in a new
      way; they used the calculated area under the curve (AUC) for the first 4 days to
      quantitatively measure the BNP load during the first critical part of the disease
      state. Their rationale was a suspicion that early BNP load is a marker of the
      severity of the ictus and will influence the subsequent course of the disease by
      disturbing the fluid and salt balance. METHODS: The study included 156 patients
      with acute spontaneous subarachnoid hemorrhage (SAH). Mean patient age was 59.8
      +/- 11.2 years, and 105 (67%) of the patients were female. An aneurysm was found
      in 138 patients. A total of 82 aneurysms were treated by endovascular coiling, 50
      were treated by surgery, and 6 were untreated. At the time of admission, serum
      samples were collected for troponin-I analysis and for the N-terminal prohormone
      of BNP (NT-proBNP); daily thereafter, samples were collected for the NT-proBNP
      analysis. The cumulative BNP load was calculated as the AUC for NT-proBNP during
      the first 4 days. The following variables were studied in terms of their
      influence on the AUC for NT-proBNP: sex, age, World Federation of Neurosurgical
      Societies grade of SAH, Fisher grade, angiographic result, treatment of aneurysm,
      clinical neurological deterioration, verified infections, vasospasm treatment,
      and 6-month outcome. RESULTS: The AUC for NT-proBNP was larger when variables
      indicated a more severe SAH. These variables were higher Fisher and World
      Federation of Neurosurgical Societies grades, high levels of troponin-I at
      admission, an aneurysm, neurological deficits, and infections. The AUC for NT
      proBNP was also larger among women, older patients, and patients with poor
      outcomes. Linear regression showed that the best predicting model for large AUC
      for NT-proBNP was the combination of the following: female sex, high levels of
      troponin-I, an aneurysm, neurological deficits, and advanced age. CONCLUSIONS:
      The cumulative BNP load during the first days after SAH can be predicted by
      variables describing the severity of the disease already known at the time of
      admission. This information can be used to identify patients at risk for an
      adverse course of the disease.

PMID- 24093630
TI  - Proteasome inhibition with bortezomib induces cell death in GBM stem-like cells
      and temozolomide-resistant glioma cell lines, but stimulates GBM stem-like cells'
      VEGF production and angiogenesis.
AB  - OBJECT: Recurrent malignant gliomas have inherent resistance to traditional
      chemotherapy. Novel therapies target specific molecular mechanisms involved in
      abnormal signaling and resistance to apoptosis. The proteasome is a key regulator
      of multiple cellular functions, and its inhibition in malignant astrocytic lines
      causes cell growth arrest and apoptotic cell death. The proteasome inhibitor
      bortezomib was reported to have very good in vitro activity against malignant
      glioma cell lines, with modest activity in animal models as well as in clinical
      trials as a single agent. In this paper, the authors describe the multiple
      effects of bortezomib in both in vitro and in vivo glioma models and offer a
      novel explanation for its seeming lack of activity. METHODS: Glioma stem-like
      cells (GSCs) were obtained from resected glioblastomas (GBMs) at surgery and
      expanded in culture. Stable glioma cell lines (U21 and D54) as well as
      temozolomide (TMZ)-resistant glioma cells derived from U251 and D54-MG were also
      cultured. GSCs from 2 different tumors, as well as D54 and U251 cells, were
      treated with bortezomib, and the effect of the drug was measured using an XTT
      cell viability assay. The activity of bortezomib was then determined in D54-MG
      and/or U251 cells using apoptosis analysis as well as caspase-3 activity and
      proteasome activity measurements. Human glioma xenograft models were created in
      nude mice by subcutaneous injection. Bevacizumab was administered via
      intraperitoneal injection at a dose of 5 mg/kg daily. Bortezomib was administered
      by intraperitoneal injection 1 hour after bevacizumab administration in doses of
      at a dose of 0.35 mg/kg on days 1, 4, 8, and 11 every 21 days. Tumors were
      measured twice weekly. RESULTS: Bortezomib induced caspase-3 activation and
      apoptotic cell death in stable glioma cell lines and in glioma stem-like cells
      (GSCs) derived from malignant tumor specimens Furthermore, TMZ-resistant glioma
      cell lines retained susceptibility to the proteasome inhibition. The bortezomib
      activity was directly proportional with the cells' baseline proteasome activity.
      The proteasome inhibition stimulated both hypoxia-inducible factor (HIF)-1alpha
      and vascular endothelial growth factor (VEGF) production in malignant GSCs. As
      such, the VEGF produced by GSCs stimulated endothelial cell growth, an effect
      that could be prevented by the addition of bevacizumab (VEGF antibody) to the
      media. Similarly, administration of bortezomib and bevacizumab to athymic mice
      carrying subcutaneous malignant glioma xenografts resulted in greater tumor
      inhibition and greater improvement in survival than administration of either drug
      alone. These data indicate that simultaneous proteasome inhibition and VEGF
      blockade offer increased benefit as a strategy for malignant glioma therapy.
      CONCLUSIONS: The results of this study indicate that combination therapies based
      on bortezomib and bevacizumab might offer an increased benefit when the two
      agents are used in combination. These drugs have a complementary mechanism of
      action and therefore can be used together to treat TMZ-resistant malignant
      gliomas.

PMID- 24093632
TI  - Subarachnoid hemorrhage.

PMID- 24093633
TI  - Caseload as a factor for outcome in aneurysmal subarachnoid hemorrhage: a
      systematic review and meta-analysis.
AB  - OBJECT: Increasing evidence exists that treatment of complex medical conditions
      in high-volume centers is found to improve outcome. Patients with subarachnoid
      hemorrhage (SAH), a complex disease, probably also benefit from treatment at a
      high-volume center. The authors aimed to determine, based on published
      literature, whether a higher hospital caseload is associated with improved
      outcomes of patients undergoing treatment after aneurysmal subarachnoid
      hemorrhage. METHODS: The authors identified studies from MEDLINE, Embase, and the
      Cochrane Library up to September 28, 2012, that evaluated outcome in high-volume
      versus low-volume centers in patients with SAH who were treated by either
      clipping or endovascular coiling. No language restrictions were set. The compared
      outcome measure was in-hospital mortality. Mortality in studies was pooled in a
      random effects meta-analysis. Study quality was reported according to the GRADE
      (Grading of Recommendations Assessment, Development and Evaluation) criteria.
      RESULTS: Four articles were included in this analysis, representing 36,600
      patients. The quality of studies was graded low in 3 and very low in 1. Meta
      analysis using a random effects model showed a decrease in hospital mortality (OR
      0.77 [95% CI 0.60-0.97]; p = 0.00; I(2) = 91%) in high-volume hospitals treating
      SAH patients. Sensitivity analysis revealed the relative weight of the 1 low
      quality study. Removal of the study with very low quality increased the effect
      size of the meta-analysis to an OR of 0.68 (95% CI 0.56-0.84; p = 0.00; I(2) =
      86%). The definition of hospital volume differed among studies. Cutoffs and
      dichotomizations were used as well as division in quartiles. In 1 study, low
      volume was defined as 9 or fewer patients yearly, whereas in another it was
      defined as fewer than 30 patients yearly. Similarly, 1 study defined high volume
      as more than 20 patients annually, and another defined it as more than 50
      patients a year. For comparability between studies, recalculation was done with
      dichotomized data if available. Cross et al., 2003 (low volume <= 18, high volume
      >= 19) and Johnston, 2000 (low volume <= 31, high volume >= 32) provided core
      data for recalculation. The overall results of this analysis revealed an OR of
      0.85 (95% CI 0.72-0.99; p = 0.00; I(2) = 87%). CONCLUSIONS: Despite the
      shortcomings of this study, the mortality rate was lower in hospitals with a
      larger caseload. Limitations of the meta-analysis are the not uniform cutoff
      values and uncertainty about case mix.

PMID- 24093635
TI  - Knowledge, attitudes, and practices regarding rabies in Filipinos following
      implementation of the Bohol Rabies Prevention and Elimination Programme.
AB  - Knowledge, attitudes, and practices (KAP) regarding rabies in Bohol, Philippines
      were assessed following introduction of the Bohol Rabies Prevention and
      Elimination Programme. A cross-sectional questionnaire was administered to 460
      households chosen utilizing the WHO's Expanded Programme on Immunization coverage
      cluster survey technique with population proportionate to size. Scores for KAP
      were evaluated using linear regression. The majority of households had heard of
      rabies (94%); however, specific knowledge of rabies was limited. Only 18% knew to
      report a suspected rabid dog to the authorities. In multivariate analyses, having
      known someone with rabies had the greatest effect on knowledge scores. Employment
      (professional or non-professional) had the greatest effect on attitudes scores,
      and only the knowledge score was significantly associated with higher practices
      scores. Several factors, notably, personal experience with rabies, affect KAP in
      Bohol. The programme should continue to focus on education and include personal
      accounts to underscore why rabies prevention and control is so important.

PMID- 24093634
TI  - Genome-wide identification of WRKY45-regulated genes that mediate
      benzothiadiazole-induced defense responses in rice.
AB  - BACKGROUND: The rice transcription factor WRKY45 plays a crucial role in
      salicylic acid (SA)/benzothiadiazole (BTH)-induced disease resistance. Its
      knockdown severely reduces BTH-induced resistance to the fungal pathogen
      Magnaporthe oryzae and the bacterial pathogen Xanthomonas oryzae pv. oryzae
      (Xoo). Conversely, overexpression of WRKY45 induces extremely strong resistance
      to both of these pathogens. To elucidate the molecular basis of WRKY45-dependent
      disease resistance, we analyzed WRKY45-regulated gene expression using rice
      transformants and a transient gene expression system. RESULTS: We conducted a
      microarray analysis using WRKY45-knockdown (WRKY45-kd) rice plants, and
      identified WRKY45-dependent genes among the BTH-responsive genes. The BTH
      responsiveness of 260 genes was dependent on WRKY45. Among these, 220 genes
      (85%), many of which encoded PR proteins and proteins associated with secondary
      metabolism, were upregulated by BTH. Only a small portion of these genes
      overlapped with those regulated by OsNPR1/NH1, supporting the idea that the rice
      SA pathway branches into WRKY45- regulated and OsNPR1/NH1-regulated subpathways.
      Dexamethazone-induced expression of myc-tagged WRKY45 in rice immediately
      upregulated transcription of endogenous WRKY45 and genes encoding the
      transcription factors WRKY62, OsNAC4, and HSF1, all of which have been reported
      to have defense-related functions. This was followed by upregulation of defense
      genes encoding PR proteins and secondary metabolic enzymes. Many of these genes
      were also induced after M. oryzae infection. Their temporal transcription
      patterns were consistent with those after dexamethazone-induced WRKY45
      expression. In a transient expression system consisting of particle bombardment
      of rice coleoptiles, WRKY45 acted as an effector to trans-activate reporter genes
      in which the luciferase coding sequence was fused to upstream and intragenic
      sequences of WRKY62 and OsNAC4. Trans-activation of transcription occurred
      through a W-box-containing sequence upstream of OsNAC4 and mutations in the W
      boxes abolished the trans-activation. CONCLUSIONS: These data suggest a role of
      WRKY45 in BTH-induced disease resistance as a master regulator of the
      transcriptional cascade regulating defense responses in one of two branches in
      the rice SA pathway.

PMID- 24093636
TI  - Recombinant lipoproteins reinforce cytotoxicity of doxorubicin to hepatocellular
      carcinoma.
AB  - Cancer nanotherapeutics are changing the landscape of tumor treatment and used to
      circumvent limitations of conventional chemotherapy, such as non-specificity and
      low bioavailability. Reconstituted high density lipoproteins (rHDL) system is one
      of the most promising targeting delivery systems of chemotherapeutic drugs toward
      tumors. Here, we developed recombined high-density lipoprotein which can be
      functionalized to deliver doxorubicin intracellular with a higher efficiency. The
      cellular viability assay showed that the rHDL/Dox nanovectors had an enhanced
      efficiency in inhibiting the cell viability of hepatocellular carcinoma cell
      lines HepG2 and SMMC-7721. FACS and confocal microscopy was used to observe the
      doxorubicin delivery into cancer cells. Intracellular drug accumulation analysis
      confirmed that treatment of rHDL/Dox nanovectors resulted in higher intracellular
      doxorubicin concentration to the levels exceeding that of free drug. On the
      premise of efficient drug delivery, rHDL/Dox nanovectors have been preliminarily
      demonstrated effective inducing of cytotoxic effect and cell apoptosis to both of
      the cell lines in vitro. Tissue distribution experiment showed that rHDL/Dox
      nanovectors could also deliver doxorubicin to liver effectively. So, we proposed
      that this lipoprotein-based strategy holds promise for a safer and more efficient
      delivery of chemotherapeutic agents in the treatment of hepatocellular carcinoma.

PMID- 24093637
TI  - MFSPSSMpred: identifying short disorder-to-order binding regions in disordered
      proteins based on contextual local evolutionary conservation.
AB  - BACKGROUND: Molecular recognition features (MoRFs) are short binding regions
      located in longer intrinsically disordered protein regions. Although these short
      regions lack a stable structure in the natural state, they readily undergo
      disorder-to-order transitions upon binding to their partner molecules. MoRFs play
      critical roles in the molecular interaction network of a cell, and are associated
      with many human genetic diseases. Therefore, identification of MoRFs is an
      important step in understanding functional aspects of these proteins and in
      finding applications in drug design. RESULTS: Here, we propose a novel method for
      identifying MoRFs, named as MFSPSSMpred (Masked, Filtered and Smoothed Position
      Specific Scoring Matrix-based Predictor). Firstly, a masking method is used to
      calculate the average local conservation scores of residues within a masking
      window length in the position-specific scoring matrix (PSSM). Then, the scores
      below the average are filtered out. Finally, a smoothing method is used to
      incorporate the features of flanking regions for each residue to prepare the
      feature sets for prediction. Our method employs no predicted results from other
      classifiers as input, i.e., all features used in this method are extracted from
      the PSSM of sequence only. Experimental results show that, comparing with other
      methods tested on the same datasets, our method achieves the best performance:
      achieving 0.004~0.079 higher AUC than other methods when tested on TEST419, and
      achieving 0.045~0.212 higher AUC than other methods when tested on TEST2012. In
      addition, when tested on an independent membrane proteins-related dataset,
      MFSPSSMpred significantly outperformed the existing predictor MoRFpred.
      CONCLUSIONS: This study suggests that: 1) amino acid composition and
      physicochemical properties in the flanking regions of MoRFs are very different
      from those in the general non-MoRF regions; 2) MoRFs contain both highly
      conserved residues and highly variable residues and, on the whole, are highly
      locally conserved; and 3) combining contextual information with local
      conservation information of residues facilitates the prediction of MoRFs.

PMID- 24093638
TI  - Bronchus-associated lymphoid tissue in pulmonary hypertension produces pathologic
      autoantibodies.
AB  - RATIONALE: Autoimmunity has long been associated with pulmonary hypertension.
      Bronchus-associated lymphoid tissue plays important roles in antigen sampling and
      self-tolerance during infection and inflammation. OBJECTIVES: We reasoned that
      activated bronchus-associated lymphoid tissue would be evident in rats with
      pulmonary hypertension, and that loss of self-tolerance would result in
      production of pathologic autoantibodies that drive vascular remodeling. METHODS:
      We used animal models, histology, and gene expression assays to evaluate the role
      of bronchus-associated lymphoid tissue in pulmonary hypertension. MEASUREMENTS
      AND MAIN RESULTS: Bronchus-associated lymphoid tissue was more numerous, larger,
      and more active in pulmonary hypertension compared with control animals. We found
      dendritic cells in and around lymphoid tissue, which were composed of CD3(+) T
      cells over a core of CD45RA(+) B cells. Antirat IgG and plasma from rats with
      pulmonary hypertension decorated B cells in lymphoid tissue, resistance vessels,
      and adventitia of large vessels. Lymphoid tissue in diseased rats was
      vascularized by aquaporin-1(+) high endothelial venules and vascular cell
      adhesion molecule-positive vessels. Autoantibodies are produced in bronchus
      associated lymphoid tissue and, when bound to pulmonary adventitial fibroblasts,
      change their phenotype to one that may promote inflammation. Passive transfer of
      autoantibodies into rats caused pulmonary vascular remodeling and pulmonary
      hypertension. Diminution of lymphoid tissue reversed pulmonary hypertension,
      whereas immunologic blockade of CCR7 worsened pulmonary hypertension and hastened
      its onset. CONCLUSIONS: Bronchus-associated lymphoid tissue expands in pulmonary
      hypertension and is autoimmunologically active. Loss of self-tolerance
      contributes to pulmonary vascular remodeling and pulmonary hypertension. Lymphoid
      tissue-directed therapies may be beneficial in treating pulmonary hypertension.

PMID- 24093639
TI  - Predicting performance and performance satisfaction: mindfulness and beliefs
      about the ability to deal with social barriers in sport.
AB  - This research investigates the role of beliefs about the ability to deal with
      specific social barriers and its relationships to mindfulness, football
      performance, and satisfaction with one's own and team performance. Study 1 aimed
      at eliciting these social barriers. Study 2 tested (i) whether self-efficacy
      referring to social barriers would predict performance over and above task
      related self-efficacy and collective efficacy and (ii) the mediating role of self
      efficacy to overcome social barriers in the relationship between mindfulness and
      performance. Participants were football (soccer) players aged 16-21 years (Study
      1: N=30; Study 2: N=101, longitudinal sample: n=88). Study 1 resulted in
      eliciting 82 social barriers referring to team, peer leadership, and coaches.
      Study 2 showed that task-related self-efficacy and collective efficacy explained
      performance satisfaction at seven-month follow-up, whereas self-efficacy
      referring to social barriers explained shooting performance at seven-month follow
      up. Indirect associations between mindfulness and performance were found with
      three types of self-efficacy referring to social barriers, operating as parallel
      mediators. Results provide evidence for the role of beliefs about the ability to
      cope with social barriers and show a complex interplay between different types of
      self-efficacy and collective efficacy in predicting team sport performance.

PMID- 24093640
TI  - Thyroid cancer complicating familial adenomatous polyposis: mutation spectrum of
      at-risk individuals.
AB  - BACKGROUND: Lifetime risk of thyroid cancer associated with FAP has been reported
      as 1-2%. The mean age at diagnosis of thyroid carcinoma in FAP has been reported
      at 28 years. The aims of this paper are to better understand gene mutations
      associated with thyroid cancer and refine surveillance recommendations for
      patients with FAP. METHODS: We performed a search in Pubmed, Ovid Medline and
      Embase with the terms ("Thyroid Gland"[Mesh] OR "Thyroid Neoplasms"[Mesh]) AND
      "Adenomatous Polyposis Coli"[Meshdenomatous Polyposis Coli"[Mesh] to identify
      subjects with thyroid cancer and FAP. As a reference group for APC mutations in
      the unselected FAP population, we used the UMD-APC database referenced in the
      Orphanet portal, which includes APC mutation data on 2040 individuals with FAP.
      RESULTS: There were 115 reported cases of thyroid cancer in patients with FAP (95
      female: 11 male) with an average age of 29.2 years. Gene mutation testing results
      were reported in 48 patients. On comparing the prevalence of APC mutation in the
      population of FAP patients with thyroid cancer and the prevalence of the same
      mutation in the reference population an increased odds ratio was evident in
      individuals harboring an APC mutation at codon 1061 (OR: CI 4.1: 1.7-8.9).
      Analysis of the prevalence of thyroid cancer in individuals with FAP segregated
      by the region of the gene affected shows an increased risk of thyroid cancer in
      individuals harboring mutations proximal to codon 512 (OR 2.6, p 0.0099).
      CONCLUSIONS: There is increased risk for thyroid cancer in individuals with APC
      mutations at the 5' end (proximal to codon 528) along with the established high
      risk group harboring mutation at codon 1061. It is suggested that these patients
      might benefit from directed surveillance by annual ultrasound from age 18 years
      onwards.

PMID- 24093644
TI  - The triflic acid-mediated cyclization reactions of N-cinnamoyl-1-naphthylamines.
AB  - N-cinnamoyl-1-naphthylamines undergo a cyclization reaction with triflic acid to
      form 4-phenyl-3,4-dihydro-1H-naphth[1,8-bc]azepin-2-ones and 4-phenyl-3,4-dihydro
      1H-benzo[h]quinolin-2-ones. However, the N-benzyl analogues also undergo a unique
      cascade reaction to form novel heptacyclic structures via a 1,2-addition followed
      by a 4-addition to the naphthalene. With an electron-rich N-benzyl substituent,
      the heptacycle is the sole product.

PMID- 24093643
TI  - The adverse effect of emergency department crowding on compliance with the
      resuscitation bundle in the management of severe sepsis and septic shock.
AB  - INTRODUCTION: The aim of this study is to evaluate the effects of emergency
      department (ED) crowding on the implementation of tasks in the early
      resuscitation bundle during acute care of patients with severe sepsis and septic
      shock, as recommended by the Surviving Sepsis Campaign guidelines. METHODS: We
      analyzed the sepsis registry from August 2008 to March 2012 for patients
      presenting to an ED of a tertiary urban hospital and meeting the criteria for
      severe sepsis or septic shock. The ED occupancy rate, which was defined as the
      total number of patients in the ED divided by the total number of ED beds, was
      used for measuring the degree of ED crowding. It was categorized into three
      groups (low; intermediate; high crowding). The primary endpoint was the overall
      compliance with the entire resuscitation bundle. RESULTS: A total of 770 patients
      were enrolled. Of the eligible patients, 276 patients were assigned to the low
      crowding group, 250 patients to the intermediate crowding group, and 244 patients
      to the high crowding group (ED occupancy rate: <= 115; 116-149; >= 150%). There
      was significant difference in compliance rates among the three groups (31.9% in
      the low crowding group, 24.4% in the intermediate crowding group, and 16.4% in
      the high crowding group, P < 0.001). In a multivariate model, the high crowding
      group had a significant association with lower compliance (adjusted odds ratio
      (OR), 0.44; 95% confidence interval (CI), 0.26 to 0.76; P = 0.003). When the ED
      occupancy rate was included as a continuous variable in the model, it had also a
      negative correlation with the overall compliance (OR of 10% increase of the ED
      occupancy rate, 0.90; 95% CI, 0.84 to 0.96, P = 0.002). CONCLUSIONS: ED crowding
      was significantly associated with lower compliance with the entire resuscitation
      bundle and decreased likelihood of the timely implementation of the bundle
      elements.

PMID- 24093645
TI  - InCl3 catalyzed highly diastereoselective [3 + 2] cycloaddition of 1,2
      cyclopropanated sugars with aldehydes: a straightforward synthesis of
      persubstituted bis-tetrahydrofurans and perhydrofuro[2,3-b]pyrans.
AB  - A mild and efficient strategy for the construction of persubstituted bis
      tetrahydrofuran and perhydrofuro[2,3-b]pyran derivatives has been developed.
      Persubstituted cyclization products were obtained in good to excellent yields.
      The [3 + 2] cycloaddition of 1,2-cyclopropanated sugars with aldehydes in the
      presence of InCl3 is highly diastereoselective. 

PMID- 24093646
TI  - Reinforcement of a sugar-based bolaamphiphile/functionalized graphene oxide
      composite gel: rheological and electrochemical properties.
AB  - A sugar-based bolaamphiphile/graphene oxide composite hydrogel has been prepared
      using simple mixing. Unlike the corresponding sugar-based native gel, the
      composite gel exhibits a fibrillar structure with a 10-20 nm fiber diameter. The
      composite gel forms an interdigitated bilayer structure incorporating
      intermolecular hydrogen-bonding interactions. The composite gel formation did not
      change the beneficial electrical properties of graphene offering the potential
      for integration of this new material into electronic systems. Interestingly, the
      mechanical and electrochemical properties of the composite gel are both
      dramatically enhanced when compared to the native gel, thereby reflecting that
      the functionalized graphene oxide layers are efficiently intercalated within the
      composite gel structure. 

PMID- 24093647
TI  - Complications of general anesthesia.
AB  - A summary of complications associated with general anesthesia including their
      incidence, mechanism, risk factors, prevention strategies, and management is
      presented.

PMID- 24093648
TI  - A primer on local anesthetics for plastic surgery.
AB  - This article provides some insight into the basic science and concepts relevant
      to the use of local anesthetics by clinicians in the management of their
      patients, including a brief history of the development of local anesthetics and
      their physical properties, effectiveness, uses, limitations, and safety
      considerations. A generalized overview of the mechanism of action is also
      provided. The molecular detail of local anesthetics and voltage-gated ion
      channels can form the basis of understanding of (1) future developments in this
      area, and (2) toxicity. Most of the peer-reviewed literature related to this
      topic stems from work in adult humans and animals.

PMID- 24093650
TI  - Local anesthetics for skin grafting and local flaps.
AB  - In plastic surgery, there are many procedures that can be performed using local
      instead of general anesthesia. Not only can this help mitigate health care costs,
      but precious operating-room resources can also be directed to areas of greater
      need. Common procedures that can be performed under local anesthetics include
      skin grafts and local flaps. However, as not all patients are suitable for local
      anesthesia, careful patient selection is necessary to maintain the standard of
      care. This article describes the detailed surgical approach to using local
      anesthetics for skin grafts and local flaps.

PMID- 24093649
TI  - Costs of regional and general anesthesia: what the plastic surgeon needs to know.
AB  - Although regional anesthesia techniques seem to expand the opportunity for cost
      savings when executing plastic surgery procedures, cost allocation is not a
      simple business. Equivalence must first be demonstrated, and the patient's
      perception is integral to assigning value to an intervention. Opportunity costs
      cannot be ignored when the plastic surgeon assumes the role of the
      anesthesiologist. Most importantly, the system must be modified to optimize the
      cost savings realized through the intervention. This article presents an in-depth
      look into the multiple factors that must be taken into consideration when
      assessing costs related to anesthesia.

PMID- 24093651
TI  - Peripheral nerve blocks for distal extremity surgery.
AB  - Peripheral nerve block is well suited for distal extremity surgery. Blocking the
      nerves at the distal extremity is easily done. It does not require ultrasound or
      stimulators to identify the nerve. Blocking nerves in the distal extremity is
      safe with low risk of toxicity. The effect of the nerve block is limited to the
      distribution of the nerve. The distal nerves in the lower extremity are sensory
      branches of the sciatic nerve. This provides a sensory block only. This has the
      advantage of allowing the patient to actively contract tendons in the foot and
      ambulate more quickly after surgery. 

PMID- 24093652
TI  - Cubital tunnel release using local anesthesia.
AB  - This article discusses an alternative approach to general anesthesia with the use
      of local anesthesia in minor operating procedure suites when performing in situ
      decompression of cubital tunnel syndrome for those patients who have mild to
      moderately severe symptoms and for those who fail to respond to conservative
      measures. Anterior transposition can easily be performed in the same setting if
      indicated all with local anesthesia. 

PMID- 24093653
TI  - Hand surgery using local anesthesia.
AB  - Most hand traumas and elective surgical disorders of the hand can be treated
      quickly, easily, inexpensively, and effectively in an outpatient clinic. Although
      many surgeons prefer general anesthesia, the senior author routinely uses local
      anesthesia without sedation almost exclusively for carpal and cubital tunnel
      release, fasciectomy, arthrodesis, arthroplasty, synovectomy, and trauma,
      including the repair of tendons, nerves, ligaments, fractures, and soft tissue
      defects. After completing more than 10,000 procedures, the authors have found
      great benefits through the use of local anesthesia, which are detailed in the
      article. 

PMID- 24093654
TI  - Breast surgery under local anesthesia: second-stage implant exchange, nipple flap
      reconstruction, and breast augmentation.
AB  - Breast reconstruction can be performed safely with local anesthesia. Utilization
      of the star flap method in conjunction with tattooing successfully provides
      optimal aesthetic results without the need for an additional donor site. When
      tissue expander to silicon implant exchange is part of the operative plan, use of
      triple antibiotic irrigation as well as the Keller Funnel is recommended. Breast
      augmentation and breast augmentation-mastopexy can also be performed with good
      results under local anesthetic in a private operating room setting. All other
      operative conditions, including sterility and sound operative surgical
      techniques, should be the mainstay of any practice. 

PMID- 24093655
TI  - Tumescent liposuction.
AB  - The evolution of liposuction has been multidisciplinary. The tumescent variant
      was developed using dilute local lidocaine and epinephrine and was meant to
      specifically exclude additional intravenous sedation, regional or general
      anesthesia, and intravenous fluids. Clinical pharmacology, pathophysiology, and
      safety studies are reviewed in this article. Tumescent formulations for varied
      anatomic sites are discussed, as well as other indications for tumescent
      anesthesia.

PMID- 24093656
TI  - Hair transplant and local anesthetics.
AB  - Hair restoration is an art and a science that requires an experienced and
      dedicated surgeon and team to achieve consistently superior outcomes. In addition
      to discussion of local anesthetic in use for hair restoration, this article
      emphasizes the pearls and pitfalls that are involved at every phase of the
      procedure including judgment, hairline design, donor harvesting, recipient-site
      creation, graft preparation, and graft placement. Two recent advances in the
      field are highlighted: the use of regenerative medicine (platelet-rich plasma and
      ACell), and developments in follicular-unit extraction as an alternative to
      traditional linear donor harvesting.

PMID- 24093657
TI  - Rhinoplasty with intravenous and local anesthesia.
AB  - Procedural sedation for a rhinoplasty, like any procedure, relies on careful
      patient selection and patient and surgeon compliance. Patients should have an
      American Society of Anesthesia (ASA) score of 1 or 2, with a possibly well
      controlled 3 also acceptable, and should be devoid of certain comorbidities,
      including obstructive sleep apnea, gastroesophageal reflux disease, and obesity
      (body mass index >=35). Before the procedure begins, clinicians must explicitly
      communicate to patients that they will feel no pain; however, because they are
      being sedated, they may know what is occurring during surgery, but they should
      not care. A common misconception about sedation is that it involves general
      anesthesia without an airway. Clinicians must reassure patients that the
      anesthetist will be with them the entire time, and any discomfort can be dealt
      with immediately and the anesthesia titrated to an acceptable level. 

PMID- 24093658
TI  - Oculoplastic surgery.
AB  - Esthetic and functional surgery in the periocular region falls into the domain of
      oculoplastic surgeons, as well as plastic surgeons and otorhinolaryngologists
      with training in facial plastic surgery. This article provides a description of 8
      common eyelid procedures that are routinely performed under local anesthesia,
      with or without mild intravenous sedation. Serious complications are rare. The
      rate of postoperative infection in the highly vascularized eyelid tissues is less
      than 1% in our experience. 

PMID- 24093659
TI  - Cosmetic face, neck, and brow lifts with local anesthesia.
AB  - The sections on the face, neck, and brow include descriptions of facelift, neck
      lift, and open brow lift techniques, anesthesia, treatment goals, procedural
      approaches, complications, management, preoperative and postoperative care,
      rehabilitation, recovery, and outcomes. The approach to facial rejuvenation the
      midface and periorbital area is detailed. These operations are often and easily
      performed entirely with the use of local anesthesia and mild oral sedation. There
      are very high satisfaction rates.

PMID- 24093660
TI  - Local anesthesia for otoplasty in children.
AB  - Otoplasty can be performed safely and effectively under local anesthesia in
      children as young as 5 years of age. Child preparation, local anesthetics,
      detailed infiltration technique, surgical procedure, and complications are
      discussed.

PMID- 24093662
TI  - Can inherited thrombophilia modulate the clinical phenotype of patients with
      antiphospholipid syndrome?
AB  - OBJECTIVES: The current case-control study was aimed to determine the prevalence
      and the clinical significance of inherited thrombophilia - factor V Leiden and
      G20210A prothrombin polymorphisms - in patients with antiphospholipid syndrome
      (APS). METHODS: 100 patients with APS (77 with primary APS and 23 with systemic
      lupus erythematosus [SLE]-APS), and 100 patients with first lower extremity deep
      venous thrombosis (DVT), and 200 healthy individuals as a control groups were
      analysed. Patients and control group were tested for factor V Leiden and
      prothrombin G20210A gene polymorphism. RESULTS: Factor V Leiden variant was found
      in 1% of APS patients, in 3% of healthy individuals (p=0.49), and 16% of patients
      with first DVT (p<0.0005). Prothrombin gene polymorphism was found in 6% of APS
      patients and in 2.5% of healthy subjects (p=0.21), and 13% of patients with DVT
      (p=0.14). In primary APS patients, factor V Leiden was present in 1.3% (1/77) and
      prothrombin gene polymorphism in 6.5% (5/77). No patient with SLE-APS had factor
      V Leiden and prothrombin gene variant was present in only one patient (4.3%).
      Patients with prothrombin polymorphism had higher prevalence of venous
      thrombosis, with no statistical significance (80% vs. 47.9%, p=0.35). There were
      no differences in the prevalence of recurrent thrombosis before or after APS
      diagnosis in patients with or without prothrombin gene polymorphism. CONCLUSIONS:
      Factor V Leiden and G20210A prothrombin variant seem to play no role in either
      the development of APS or in the type of involved vessel, with no increased risk
      of re-thrombosis during follow-up.

PMID- 24093663
TI  - Soluble antioxidant compounds regenerate the antioxidants bound to insoluble
      parts of foods.
AB  - This study aimed to investigate the regeneration potential of antioxidant
      capacity of an insoluble food matrix. Investigations were performed in vitro with
      several food matrices rich in dietary fiber (DF) and bound antioxidants. After
      removal of the soluble fraction, the antioxidant capacity (AC) of the insoluble
      fraction was measured by the QUENCHER procedure using ABTS(*+) or DPPH(*)
      radicals. After measurement, the insoluble residue was washed out to remove the
      excess of radicals and treated with pure antioxidant solution or antioxidant-rich
      beverage to regenerate depleted antioxidants on the fiber. Results revealed that
      the antioxidant capacity of compounds chemically bound to the insoluble moiety
      could be reconstituted in the presence of other hydrogen-donating substances in
      the liquid phase. Regeneration efficiency was found to range between 21.5 and
      154.3% depending on the type of insoluble food matrix and regeneration agent.
      Among the food matrices studied, cereal products were found to have slightly
      higher regeneration efficiency, whereas antioxidant-rich beverages were more
      effective than pure antioxidants as regeneration agents. Taking wheat bran as
      reference insoluble material, the regeneration abilities of beverages were in the
      following order: green tea > espresso coffee > black tea > instant coffee >
      orange juice > red wine. These results highlighted the possible physiological
      relevance of antioxidants bound to the insoluble food material in the
      gastrointestinal tract. During the digestion process they could react with the
      free radicals and at the same time they can be regenerated by other soluble
      antioxidant compounds present in the meal. 

PMID- 24093664
TI  - Volumizing hyaluronic acid filler for midface volume deficit: 2-year results from
      a pivotal single-blind randomized controlled study.
AB  - BACKGROUND: Hyaluronic acid (HA) gels are commonly used to correct age-related
      midface volume deficit (MVD), yet the Food and Drug Administration has not
      specifically approved them for this purpose. OBJECTIVE: To study the safety and
      effectiveness of a new 20-mg/mL HA gel (VYC-20L) specifically formulated and
      optimized for mid-face volumizing. METHODS AND MATERIALS: A multicenter, single
      blind, controlled study randomized 235 subjects aged 35 to 65 with MVD to a
      treatment group and 47 to a no-treatment control group. Responders were defined
      as subjects who achieved improvement of 1 point or more on the validated 6-point
      Mid-Face Volume Deficit Scale (MFVDS) at 6 months as rated live by two blinded
      independent evaluators. The primary endpoint required a 70% or greater treatment
      group response and a statistically significant difference (p < .001) between the
      treatment and control group responder rates. RESULTS: The primary endpoint was
      met, with 85.6% of the treatment group improving by 1 point or more on the MFVDS
      at month 6 and a statistically significant difference (p < .001) between the
      treatment and control group responder rates. Subjects tolerated VYC-20L well,
      with no unanticipated adverse device effects. Nearly half of subjects maintained
      correction for 24 months. CONCLUSION: VYC-20L is safe and effective for age
      related MVD, with correction lasting up to 2 years.

PMID- 24093666
TI  - Fine-scale spatiotemporal influences of salmon on growth and nitrogen signatures
      of Sitka spruce tree rings.
AB  - BACKGROUND: The marine-terrestrial transfer of salmon (Oncorhynchus spp.)
      provides a substantial pulse of nutrients to receiving ecosystems along the
      Pacific coast of North America and has been shown to enhance productivity and
      isotopic signatures of conifers and other riparian vegetation. An explicitly
      spatial, within-watershed investigation of the influence of salmon on conifers
      has never been previously investigated. In a small salmon-bearing watershed in
      Haida Gwaii, Canada, the transfer and distributional pattern of salmon carcasses
      into the riparian zone by black bears provided a spatial basis for investigating
      the influence of salmon on Sitka spruce tree ring growth and nitrogen isotopic
      signatures (delta(15)N) across a gradient of salmon carcass densities in relation
      to salmon escapement. RESULTS: Annual growth was found to be highest in the high
      salmon carcass zone and delta(15)N signatures closely tracked the known
      distribution of salmon carcasses at distances into the forest and upstream. Tree
      diameter demonstrated a positive relationship with delta(15)N signatures for
      trees with and without salmon carcass influence. Using an information theoretics
      approach with general linear mixed models (GLMMs), we show that salmon abundance,
      mean annual temperature and the interaction terms salmon abundance*temperature
      and salmon abundance*distance into the forest best predict tree growth. In
      addition, spatial variables (distance into forest and upstream) and their
      interaction are the strongest predictors of delta(15)N signatures. However
      patterns observed in individual trees, particularly those at increased distance
      into the forest, suggest positive relationships with historical salmon abundance.
      CONCLUSIONS: Using a replicated spatial sampling design across a sharp gradient
      in salmon nutrient loading, our study provides clear evidence that the temporal
      pattern in an allochthonous nutrient source and an interaction with temperature
      and spatial location influences conifer growth. Although salmon abundance has
      been previously linked to annual conifer growth and delta(15)N levels, our
      approach demonstrates the need to incorporate additional predictors including
      tree size and opens up the prospect of their dual use as historical proxies for
      salmon abundance.

PMID- 24093667
TI  - Nanoparticles inhibit DNA replication by binding to DNA: modeling and
      experimental validation.
AB  - Predictive models are beneficial tools for researchers to use in prioritizing
      nanoparticles (NPs) for toxicological tests, but experimental evaluation can be
      time-consuming and expensive, and thus, priority should be given to tests that
      identify the NPs most likely to be harmful. For characterization of NPs, the
      physical binding of NPs to DNA molecules is important to measure, as interference
      with DNA function may be one cause of toxicity. Here, we determined the
      interaction energy between 12 types of NPs and DNA based on the Derjaguin-Landau
      Verwey-Overbeek (DLVO) model and then predicted the affinity of the NPs for DNA.
      Using the single-molecule imaging technique known as atomic force microscopy
      (AFM), we experimentally determined the binding affinity of those NPs for DNA.
      Theoretical predictions and experimental observations of the binding affinity
      agreed well. Furthermore, the effect of NPs on DNA replication in vitro was
      investigated with the polymerase chain reaction (PCR) technique. The results
      showed that NPs with a high affinity for DNA strongly inhibited DNA replication,
      whereas NPs with low affinity had no or minimal effects on DNA replication. The
      methodology here is expected to benefit the genotoxicological testing of NPs as
      well as the design of safe NPs. 

PMID- 24093668
TI  - Quantitative DNA methylation analyses reveal stage dependent DNA methylation and
      association to clinico-pathological factors in breast tumors.
AB  - BACKGROUND: Aberrant DNA methylation of regulatory genes has frequently been
      found in human breast cancers and correlated to clinical outcome. In the present
      study we investigate stage specific changes in the DNA methylation patterns in
      order to identify valuable markers to understand how these changes affect breast
      cancer progression. METHODS: Quantitative DNA methylation analyses of 12
      candidate genes ABCB1, BRCCA1, CDKN2A, ESR1, GSTP1, IGF2, MGMT, HMLH1, PPP2R2B,
      PTEN, RASSF1A and FOXC1 was performed by pyrosequencing a series of 238 breast
      cancer tissue samples from DCIS to invasive tumors stage I to IV. RESULTS:
      Significant differences in methylation levels between the DCIS and invasive stage
      II tumors were observed for six genes RASSF1A, CDKN2A, MGMT, ABCB1, GSTP1 and
      FOXC1. RASSF1A, ABCB1 and GSTP1 showed significantly higher methylation levels in
      late stage compared to the early stage breast carcinoma. Z-score analysis
      revealed significantly lower methylation levels in DCIS and stage I tumors
      compared with stage II, III and IV tumors. Methylation levels of PTEN, PPP2R2B,
      FOXC1, ABCB1 and BRCA1 were lower in tumors harboring TP53 mutations then in
      tumors with wild type TP53. Z-score analysis showed that TP53 mutated tumors had
      significantly lower overall methylation levels compared to tumors with wild type
      TP53. Methylation levels of RASSF1A, PPP2R2B, GSTP1 and FOXC1 were higher in ER
      positive vs. ER negative tumors and methylation levels of PTEN and CDKN2A were
      higher in HER2 positive vs. HER2 negative tumors. Z-score analysis also showed
      that HER2 positive tumors had significantly higher z-scores of methylation
      compared to the HER2 negative tumors. Univariate survival analysis identifies
      methylation status of PPP2R2B as significant predictor of overall survival and
      breast cancer specific survival. CONCLUSIONS: In the present study we report that
      the level of aberrant DNA methylation is higher in late stage compared with early
      stage of invasive breast cancers and DCIS for genes mentioned above.

PMID- 24093669
TI  - Spectroscopic investigation of the noncovalent association of the nerve agent
      simulant diisopropyl methylphosphonate (DIMP) with zinc(II) porphyrins.
AB  - Organophosphonates pose a significant threat as chemical warfare agents, as well
      as environmental toxins in the form of pesticides. Thus, methodologies to sense
      and decontaminate these agents are of significant interest. Porphyrins and
      metalloporphyrins offer an excellent platform to develop chemical threat sensors
      and photochemical degradation systems. These highly conjugated planar molecules
      exhibit relatively long-lived singlet and triplet states with high quantum yields
      and also form self-associated complexes with a wide variety of molecules. A
      significant aspect of porphyrins is the ability to functionalize the peripheral
      ring system either directly to the pyrrole rings or to the bridging methine
      carbons. In this report, steady-state absorption and fluorescence are utilized to
      probe binding affinities of a series of symmetric and asymmetric zinc(II)
      metalloporphyrins for the nerve agent simulant diisopropyl methylphosphonate
      (DIMP) in hexane. The red shifts in the absorption and emission spectra observed
      for all of the metalloporphyrins probed are discussed in the frame of Gouterman's
      four orbital model and a common binding motif involving coordination between the
      metalloporphyrin and DIMP via interaction between the zinc metal center of the
      porphyrin and phosphoryl oxygen of DIMP (Zn-O?P) is proposed. 

PMID- 24093670
TI  - What's the Mtrr with your grandparents?
AB  - Reduced folate levels can cause developmental defects and megaloblastic anemia.
      Padmanabhan et al. (2013) show that mutation in mice of a folate metabolism gene,
      Mtrr, which encodes for methionine synthase reductase, causes developmental
      defects not only in the mutant progeny, but also in genetically wild-type
      descendants for up to four generations. 

PMID- 24093671
TI  - Hedonic and homeostatic overlap following fat ingestion.
AB  - Ingestion of fatty foods increases dopamine release in the substantia nigra,
      producing a positive hedonic state. Tellez et al. (2013) demonstrate that an
      intestinal signal generated by fat consumption, oleoylethanolamide, stimulates
      central dopamine activity, thus regulating the reward value of fat and
      establishing a link between caloric-homeostatic and hedonic-homeostatic
      controllers. 

PMID- 24093672
TI  - The Semaphorin 3E/PlexinD1 axis regulates macrophage inflammation in obesity.
AB  - Increased accumulation of adipose tissue macrophages in obesity propagates
      chronic inflammation that is closely associated with insulin resistance and type
      2 diabetes. Semaphorin 3E, a guidance molecule for neurons, takes on a new role
      in obesity by directing the recruitment of macrophages in visceral adipose tissue
      (Shimizu et al., 2013).

PMID- 24093673
TI  - Hereditary mtDNA heteroplasmy: a baseline for aging?
AB  - Do mtDNA mutations contribute to the aging process, or are they innocent
      bystanders? Ross et al. (2013) show that inherited mtDNA point mutations lead to
      a premature aging phenotype in mice and "prime" the maternal lineage, interacting
      with subsequent somatic mutations to cause brain malformations and shorten
      lifespan.

PMID- 24093674
TI  - Semaphorin3E-induced inflammation contributes to insulin resistance in dietary
      obesity.
AB  - Semaphorins and their receptors (plexins) are axon-guiding molecules that
      regulate the development of the nervous system during embryogenesis. Here we
      describe a previously unknown role of class 3 semaphorin E (Sema3E) in adipose
      tissue inflammation and insulin resistance. Expression of Sema3E and its receptor
      plexinD1 was upregulated in the adipose tissue of a mouse model of dietary
      obesity. Inhibition of the Sema3E-plexinD1 axis markedly reduced adipose tissue
      inflammation and improved insulin resistance in this model. Conversely,
      overexpression of Sema3E in adipose tissue provoked inflammation and insulin
      resistance. Sema3E promoted infiltration of macrophages, and this effect was
      inhibited by disrupting plexinD1 expression in macrophages. Disruption of adipose
      tissue p53 expression led to downregulation of Sema3E expression and improved
      adipose tissue inflammation. These results indicate that Sema3E acts as a
      chemoattractant for macrophages, with p53-induced upregulation of Sema3E
      expression provoking adipose tissue inflammation and systemic insulin resistance
      in association with dietary obesity.

PMID- 24093675
TI  - Neuron-derived semaphorin 3A is an early inducer of vascular permeability in
      diabetic retinopathy via neuropilin-1.
AB  - The deterioration of the inner blood-retinal barrier and consequent macular edema
      is a cardinal manifestation of diabetic retinopathy (DR) and the clinical feature
      most closely associated with loss of sight. We provide evidence from both human
      and animal studies for the critical role of the classical neuronal guidance cue,
      semaphorin 3A, in instigating pathological vascular permeability in diabetic
      retinas via its cognate receptor neuropilin-1. We reveal that semaphorin 3A is
      induced in early hyperglycemic phases of diabetes within the neuronal retina and
      precipitates initial breakdown of endothelial barrier function. We demonstrate,
      by a series of orthogonal approaches, that neutralization of semaphorin 3A
      efficiently prevents diabetes-induced retinal vascular leakage in a stage of the
      disease when vascular endothelial growth factor neutralization is inefficient.
      These observations were corroborated in Tg(Cre-Esr1)/Nrp1(flox/flox) conditional
      knockout mice. Our findings identify a therapeutic target for macular edema and
      provide further evidence for neurovascular crosstalk in the pathogenesis of DR. 

PMID- 24093677
TI  - Resveratrol improves adipose insulin signaling and reduces the inflammatory
      response in adipose tissue of rhesus monkeys on high-fat, high-sugar diet.
AB  - Obesity is associated with a chronic, low-grade, systemic inflammation that may
      contribute to the development of insulin resistance and type 2 diabetes.
      Resveratrol, a natural compound with anti-inflammatory properties, is shown to
      improve glucose tolerance and insulin sensitivity in obese mice and humans. Here,
      we tested the effect of a 2-year resveratrol administration on proinflammatory
      profile and insulin resistance caused by a high-fat, high-sugar (HFS) diet in
      white adipose tissue (WAT) from rhesus monkeys. Resveratrol supplementation (80
      and 480 mg/day for the first and second year, respectively) decreased adipocyte
      size, increased sirtuin 1 expression, decreased NF-kappaB activation, and
      improved insulin sensitivity in visceral, but not subcutaneous, WAT from HFS-fed
      animals. These effects were reproduced in 3T3-L1 adipocytes cultured in media
      supplemented with serum from monkeys fed HFS +/- resveratrol diets. In
      conclusion, chronic administration of resveratrol exerts beneficial metabolic and
      inflammatory adaptations in visceral WAT from diet-induced obese monkeys.

PMID- 24093678
TI  - AMP as a low-energy charge signal autonomously initiates assembly of AXIN-AMPK
      LKB1 complex for AMPK activation.
AB  - The AMP-activated protein kinase (AMPK) is a master regulator of metabolic
      homeostasis by sensing cellular energy status. AMPK is mainly activated via
      phosphorylation by LKB1 when cellular AMP/ADP levels are increased. However, how
      AMP/ADP brings about AMPK phosphorylation remains unclear. Here, we show that it
      is AMP, but not ADP, that drives AXIN to directly tether LKB1 to phosphorylate
      AMPK. The complex formation of AXIN-AMPK-LKB1 is greatly enhanced in glucose
      starved or AICAR-treated cells and in cell-free systems supplemented with
      exogenous AMP. Depletion of AXIN abrogated starvation-induced AMPK-LKB1
      colocalization. Importantly, adenovirus-based knockdown of AXIN in the mouse
      liver impaired AMPK activation and caused exacerbated fatty liver after
      starvation, underscoring an essential role of AXIN in AMPK activation. These
      findings demonstrate an initiating role of AMP and demonstrate that AXIN directly
      transmits AMP binding of AMPK to its activation by LKB1, uncovering the
      mechanistic route for AMP to elicit AMPK activation by LKB1.

PMID- 24093676
TI  - Canonical Nlrp3 inflammasome links systemic low-grade inflammation to functional
      decline in aging.
AB  - Despite a wealth of clinical data showing an association between inflammation and
      degenerative disorders in the elderly, the immune sensors that causally link
      systemic inflammation to aging remain unclear. Here we detail a mechanism by
      which the Nlrp3 inflammasome controls systemic low-grade age-related "sterile"
      inflammation in both periphery and brain independently of the noncanonical
      caspase-11 inflammasome. Ablation of Nlrp3 inflammasome protected mice from age
      related increases in the innate immune activation, alterations in CNS
      transcriptome, and astrogliosis. Consistent with the hypothesis that systemic low
      grade inflammation promotes age-related degenerative changes, the deficient Nlrp3
      inflammasome-mediated caspase-1 activity improved glycemic control and attenuated
      bone loss and thymic demise. Notably, IL-1 mediated only Nlrp3 inflammasome
      dependent improvement in cognitive function and motor performance in aged mice.
      These studies reveal Nlrp3 inflammasome as an upstream target that controls age
      related inflammation and offer an innovative therapeutic strategy to lower Nlrp3
      activity to delay multiple age-related chronic diseases.

PMID- 24093679
TI  - AMP is a true physiological regulator of AMP-activated protein kinase by both
      allosteric activation and enhancing net phosphorylation.
AB  - While allosteric activation of AMPK is triggered only by AMP, binding of both ADP
      and AMP has been reported to promote phosphorylation and inhibit
      dephosphorylation at Thr172. Because cellular concentrations of ADP and ATP are
      higher than AMP, it has been proposed that ADP is the physiological signal that
      promotes phosphorylation and that allosteric activation is not significant in
      vivo. However, we report that: AMP is 10-fold more potent than ADP in inhibiting
      Thr172 dephosphorylation; only AMP enhances LKB1-induced Thr172 phosphorylation;
      and AMP can cause > 10-fold allosteric activation even at concentrations 1-2
      orders of magnitude lower than ATP. We also provide evidence that allosteric
      activation by AMP can cause increased phosphorylation of acetyl-CoA carboxylase
      in intact cells under conditions in which there is no change in Thr172
      phosphorylation. Thus, AMP is a true physiological regulator of AMPK, and
      allosteric regulation is an important component of the overall activation
      mechanism.

PMID- 24093680
TI  - Glucose-induced regulation of protein import receptor Tom22 by cytosolic and
      mitochondria-bound kinases.
AB  - Most mitochondrial proteins are imported by the translocase of the outer
      mitochondrial membrane (TOM). Tom22 functions as central receptor and transfers
      preproteins to the import pore. Casein kinase 2 (CK2) constitutively
      phosphorylates the cytosolic precursor of Tom22 at Ser44 and Ser46 and, thus,
      promotes its import. It is unknown whether Tom22 is regulated under different
      metabolic conditions. We report that CK1, which is involved in glucose-induced
      signal transduction, is bound to mitochondria. CK1 phosphorylates Tom22 at Thr57
      and stimulates the assembly of Tom22 and Tom20. In contrast, protein kinase A
      (PKA), which is also activated by the addition of glucose, phosphorylates the
      precursor of Tom22 at Thr76 and impairs its import. Thus, PKA functions in an
      opposite manner to CK1 and CK2. Our results reveal that three kinases regulate
      the import and assembly of Tom22, demonstrating that the central receptor is a
      major target for the posttranslational regulation of mitochondrial protein
      import.

PMID- 24093681
TI  - Rapid versus delayed stimulation of feeding by the endogenously released AgRP
      neuron mediators GABA, NPY, and AgRP.
AB  - Agouti-related peptide (AgRP) neurons of the hypothalamus release a fast
      transmitter (GABA) in addition to neuropeptides (neuropeptide Y [NPY] and Agouti
      related peptide [AgRP]). This raises questions as to their respective functions.
      The acute activation of AgRP neurons robustly promotes food intake, while central
      injections of AgRP, NPY, or GABA agonist results in the marked escalation of food
      consumption with temporal variance. Given the orexigenic capability of all three
      of these neuroactive substances in conjunction with their coexpression in AgRP
      neurons, we looked to unravel their relative temporal role in driving food
      intake. After the acute stimulation of AgRP neurons with DREADD technology, we
      found that either GABA or NPY is required for the rapid stimulation of feeding,
      and the neuropeptide AgRP, through action on MC4 receptors, is sufficient to
      induce feeding over a delayed yet prolonged period. These studies help to
      elucidate the neurochemical mechanisms of AgRP neurons in controlling temporally
      distinct phases of eating.

PMID- 24093683
TI  - Review of the clinical effectiveness of the neuraminidase inhibitors against
      influenza B viruses.
AB  - Influenza A and B viruses cause significant morbidity and mortality worldwide
      each year. The neuraminidase inhibitors (NAIs) are the most commonly used class
      of influenza antiviral drugs for the treatment of infected patients. In vitro
      studies have shown that influenza B viruses are significantly less susceptible to
      oseltamivir and other neuraminidase inhibitors compared with influenza A viruses.
      Following analysis of published clinical studies, we show that oseltamivir does
      appear to have lower effectiveness in patients infected with influenza B virus
      compared with influenza A infected patients, but due to insufficient studies on
      zanamivir, laninamivir or peramivir, it was not possible to conclude the relative
      effectiveness of these drugs against influenza A virus compared with B virus. 

PMID- 24093682
TI  - Profiling of Glucose-Sensing Neurons Reveals that GHRH Neurons Are Activated by
      Hypoglycemia.
AB  - Comprehensive transcriptional profiling of glucose-sensing neurons is challenging
      because of low expression levels of glucokinase (Gck) and other key proteins that
      transduce a glucose signal. To overcome this, we generated and validated
      transgenic mice with a neuronal/endocrine-specific Gck promoter driving cre
      expression and mated them to mice with cre-dependent expression of an EGFP-tagged
      ribosomal protein construct (EEF1A1-LSL.EGFPL10) that can be used to map and
      profile cells. We found significant Gck expression in hypothalamic and limbic
      regions in cells that are activated following administration of glucose or 2
      deoxyglucose. Transcriptional profiling from Gck-cre/EEF1A1-LSL.EGFPL10 mice
      enriched known and previously unknown glucose-sensing populations including
      neurons expressing growth hormone releasing hormone (GHRH). Electrophysiological
      recordings show that hypoglycemia activates GHRH neurons, suggesting a
      mechanistic link between hypoglycemia and growth hormone release. These studies
      provide a means for mapping glucose-sensitive neurons and for generating
      transcriptional profiles from other cell types expressing cre in a cell-specific
      manner.

PMID- 24093685
TI  - What's your diagnosis? Migration of the Os peroneum associated with rupture of
      the peroneus longus tendon.

PMID- 24093684
TI  - Purified hepatitis B virus induces human mesangial cell proliferation and
      extracellular matrix expression in vitro.
AB  - BACKGROUND: Hepatitis B virus (HBV) induces proliferation of human mesangial
      cells (HMCs), and extracellular matrix expression through the deposition of
      immune complexes in renal tissue. However, it is unclear whether HBV can directly
      affect HMCs. In this study, the effects of purified HBV on HMC proliferation and
      extracellular matrix expression in vitro was determined. FINDINGS: HBV was
      purified using sucrose density gradient centrifugation. HMCs were co-cultured
      with purified HBV (104-106 copies/ml) for 48 h, and cell proliferation determined
      using 5-ethynyl-2'-deoxyuridine immunofluorescence assays. After HMCs were co
      cultured with 106 copies/ml purified HBV for 0, 12, 24, 36 and 48 h, expression
      of type IV collagen and fibronectin was measured using enzyme-linked
      immunosorbent assays. Three titers of purified HBV (10(4), 10(5), and 10(6)
      copies/ml) induced HMC proliferation, with the proportion of increases in cell
      numbers at 24.7 +/- 4.3, 31.2 +/- 9.4, and 36.8 +/- 7.5%, respectively. All these
      increases were significantly higher than those for the control group (13.6 +/-
      4.2%) (All p < 0.05). Purified HBV (10(6) copies/ml) significantly increased the
      levels of type IV collagen and fibronectin in supernatants compared with the
      control group at 12 and 48 h (All p < 0.05). CONCLUSIONS: Purified HBV can
      directly promote HMC proliferation and expression of type IV collagen and
      fibronectin, and could be involved in the pathogenesis of HBV-associated
      glomerulonephritis.

PMID- 24093686
TI  - Changing nature of continuing medical education.

PMID- 24093687
TI  - Late repair of combined extensor carpi radialis longus and brevis avulsion
      fractures.
AB  - Concomitant avulsion fractures of the extensor carpi radialis longus and brevis
      tendons are relatively rare injuries. The usual injury mechanism is forced
      hyperflexion to an actively extended wrist. No consensus exists regarding the
      appropriate management of this injury, with some surgeons advocating closed
      treatment and others favoring operative fixation. The authors describe a novel
      surgical technique for the late repair of combined extensor carpi radialis longus
      and brevis tendon avulsion using suture anchor repair of the extensor carpi
      radialis brevis and tenodesis of the retracted extensor carpi radialis longus to
      the brevis. 

PMID- 24093689
TI  - Vacuum-assisted closure for hand injuries.

PMID- 24093688
TI  - Short stem option for total hip arthroplasty with retained hardware.
AB  - The presence of retained femoral hardware, usually as a consequence of prior
      orthopedic trauma, has been classically presented as something that must be
      removed prior to total hip arthroplasty. However, hardware removal is not without
      risks, including pain, creation of stress risers, and refracture. The authors
      report a patient with a retained retrograde femoral nail who underwent total hip
      arthroplasty with a short, neck-preserving femoral stem used to avoid the need
      for hardware removal. Clinical results at short-term follow-up have been
      excellent. In the setting of retained hardware, the use of short stems may be a
      viable treatment option for a well-selected subgroup of patients who require
      total hip arthroplasty and when the surgeon cannot use standard implants. 

PMID- 24093690
TI  - Fluoroscopic imaging of acetabular cup position during THA through a direct
      anterior approach.
AB  - Mobile image intensifiers are more readily used to assess acetabular cup
      placement when performing a total hip arthroplasty through a direct anterior
      approach. However, patient positioning affects pelvic tilt and rotation, which in
      turn requires proper C-arm fluoroscopy adjustments for image interpretation. The
      authors provide insight into the interpretation of acetabular cup positioning
      based on the fluoroscopic images obtained to ensure appropriate cup positioning
      using the direct anterior approach for total hip arthroplasty. 

PMID- 24093691
TI  - Current concepts in the treatment of distal radial fractures.
AB  - Distal radial fractures are among the most commonly encountered traumatic
      fractures of the upper extremity. Initial trauma mechanism, fracture pattern,
      associated injuries, and patient age influence treatment and outcome. Although
      stable fractures are commonly treated conservatively, the past decade has seen
      changes in surgical practice and techniques. Indications for surgery have been
      extended and refined based on new insight into the pathophysiology of the distal
      end of the forearm and technological advances in implant design. Despite the
      frequency of this fracture, only limited higher-level evidence exists to guide
      practitioners in decision making for this injury. This article highlights key
      concepts in the treatment of distal radial fractures and summarizes current
      evidence. 

PMID- 24093693
TI  - Elbow fracture dislocation.

PMID- 24093694
TI  - Osteoid osteoma.
AB  - Osteoid osteomas consist of a nidus with surrounding sclerotic bone. The
      differential diagnosis covers a wide range of conditions due to the variable
      presentation of osteoid osteoma. The natural history is for regression to occur
      within 6 to 15 years with no treatment; however, this can be reduced to 2 to 3
      years with the use of aspirin and non-steroidal anti-inflammatory drugs. Computed
      tomography-guided percutaneous techniques, including trephine excision,
      cryoablation, radiofrequency ablation, and laser thermocoagulation, are
      described.

PMID- 24093695
TI  - Bibliometric analysis of the orthopedic literature.
AB  - Bibliometric indicators are used to assess research performance. The goal of this
      study was to explore publication output to construct a picture of orthopedics
      that may be beneficial to researchers and orthopedic specialists. All orthopedics
      articles published in 61 journals from 2000 to 2011 were retrieved from the
      Science Citation Index Expanded database. The numbers of articles, citations,
      authors, institutions, and journals were analyzed and subjected to quantitative
      and qualitative comparisons. The number of published orthopedics articles
      increased between 2000 and 2011. Articles published by authors from the United
      States always ranked first in number, although the United States' share is
      decreasing in the world literature. Authors from the United States published the
      most-cited articles and the most articles in journals with top-10 impact factors;
      moreover, the United States also had the greatest share of experts and highly
      ranked institutions. The United Kingdom, Germany, and Japan were always within
      the world's top 4 in terms of numbers of articles and citations. The shares of
      Germany, South Korea, and China among total orthopedics articles increased,
      especially that of China. In 2011, China ranked the fifth in the world, with its
      world share increasing from 0.64% in 2000 to 5.05% in 2011. However, China lags
      behind in average citations per article, top research institutions, and most
      prolific authors. According to the total citations per article, the University of
      Pittsburgh, Harvard University, and the Hospital for Special Surgery were the
      most prolific institutions. 

PMID- 24093696
TI  - Use of fine-threaded K-wires in the treatment of coronoid fractures in complex
      elbow instability.
AB  - The coronoid process is one of the main elbow constraints that provides
      ulnohumeral joint stability. Coronoid fractures may be fixed using multiple
      techniques, including transosseous sutures, screws, and plates. The goal of this
      study was to analyze the clinical and radiographic outcomes in a series of
      patients with complex elbow instability in whom coronoid fractures were repaired
      using fine-threaded K-wires. Eight men and 10 women (mean age, 47 years) were
      followed prospectively for a mean of 26 months. Surgical treatment consisted of
      open reduction and internal fixation of all fractures; radial head replacement in
      Mason III injuries; lateral collateral ligament repair in all patients; and, in
      cases of persistent instability, medial collateral ligament repair, hinged
      fixator application, or both. Coronoid fixation was performed using 2 or more
      fine-threaded K-wires, depending on the fragment size, inserted from the
      posterior aspect of the ulna and directed toward the coronoid fragment using a 1
      step fixation technique. At last follow-up, mean extension was 15 degrees , mean
      flexion was 133 degrees , mean pronation was 78 degrees , and mean supination was
      69 degrees ; mean Disabilities of the Arm, Shoulder and Hand score was 9.7, mean
      American Shoulder and Elbow Surgeons score was 85, and mean Mayo Elbow
      Performance Score was 89. According to the Mayo Elbow Performance Index, 10
      excellent, 7 good, and 1 fair result were recorded. All but 1 patient had a
      stable elbow. Fracture healing was observed in all but 1 patient. No secondary
      coronoid fragment dislocation or implant failures were reported. This study shows
      that using fine-threaded K-wires provides easy, minimally invasive, stable, and
      successful 1-step fixation that can be used to obtain osteosynthesis of coronoid
      fractures in patients with complex elbow instability. 

PMID- 24093697
TI  - Comparison of clinical results after pisiformectomy in patients with rheumatic
      versus posttraumatic osteoarthritis.
AB  - Pisotriquetral osteoarthritis is important to consider in the differential
      diagnosis of chronic ulnar-sided wrist pain. It can develop following traumatic
      injury to the pisiform or in rheumatic diseases, such as rheumatoid arthritis or
      psoriatic arthritis. It has been shown that pisiformectomy can relieve symptoms
      in cases that have not responded to nonoperative treatment, and the excision does
      not compromise the function or strength of the wrist. Most studies focus on
      posttraumatic causes of pisotriquetral osteoarthritis. In the current study,
      rheumatic causes are also considered and the outcomes are compared. This
      retrospective study included 35 patients who underwent pisiformectomy for
      pisotriquetral osteoarthritis. All patients underwent a thorough diagnostic
      evaluation to exclude other etiologies for ulnar-sided wrist pain. Radiological
      examinations including posteroanterior and lateral views of the wrist and a
      tangential view of the pisotriquetral joint were analyzed. All patients had
      excellent or very good results after pisiformectomy, with a significant reduction
      in pain. No significant difference was found in the outcomes for patients with
      rheumatic vs posttraumatic osteoarthritis. Patients with rheumatic causes of
      pisotriquetral osteoarthritis can be successfully treated with pisiformectomy.
      With respect to idiopathic causes, these patients need a longer postoperative
      period to gain full pain relief. It is important to consider the possibility of
      pisotriquetral osteoarthritis after excluding other diagnoses in patients with
      rheumatic osteoarthritis. 

PMID- 24093698
TI  - Surgical treatment of Ideberg type III glenoid fractures with associated superior
      shoulder suspensory complex injury.
AB  - Ideberg type III glenoid fractures with associated superior shoulder suspensory
      complex (SSSC) injuries are rare, and related treatments have not been reported
      in the literature. The purpose of this study was to evaluate the clinical
      outcomes of such injuries treated with open reduction and internal fixation
      (ORIF). Between July 2007 and April 2012, ten patients with Ideberg type III
      glenoid fractures were surgically treated using ORIF with 2 cannulated screws or
      a screw combined with a metacarpal plate through an anterior approach. Patients
      with associated SSSC injuries underwent ORIF with K-wires or plates. Information
      was available for 9 patients with a mean follow-up of 24.1+/-18.2 months. Mean
      bone-healing time was 8.4+/-2.2 weeks. At last follow-up, mean forward flexion of
      the operative shoulder was 157.8 degrees +/-7.5 degrees , mean external rotation
      was 62.9 degrees +/-7.9 degrees , and mean internal rotation was thoracic level
      T6+/-0.8. Mean Constant score was 84.1+/-3.7 points, which was a mean of 92.7%+/
      3.4% of that seen in the contralateral shoulder. Mean UCLA score and Disabilities
      of the Arm, Shoulder and Hand score were 33.6+/-1.7 and 16.6+/-7.7, respectively.
      The results show that Ideberg type III glenoid fractures with associated SSSC
      injuries can be successfully treated using ORIF through an anterior approach.
      Glenoid fractures and SCCC injuries should be treated simultaneously. 

PMID- 24093699
TI  - Congenital stenosis and adjacent segment disease in the cervical spine.
AB  - Symptomatic adjacent segment disease (ASD) after anterior cervical fusion (ACF)
      is reported in 25% of patients at 10 years postoperatively. Debate continues as
      to whether this degeneration is due to the natural history of the disk or the
      changed biomechanics after ACF. This study explored whether congenital stenosis
      predisposes patients to an increased incidence of ASD after ACF. A retrospective
      review of 635 patients with myelopathy or radiculopathy was performed; 364
      patients had complete records for review. Patients underwent 1- to 5-level ACF
      (94 one-level, 145 two-level, 79 three-level, 45 four-level, and 1 five-level).
      Radiographs were evaluated for bony congenital stenosis using validated
      parameters, and ASD was measured according to Hilibrand's criteria and correlated
      with symptomatic ASD. Congenital stenosis was found in 21.7% of patients and
      radiographic ASD in 33.5%, with a significant association between these
      parameters. However, symptomatic ASD occurred in 11.8% of patients; no
      association between congenital stenosis and symptomatic ASD or myelopathy and ASD
      was found. Clinical results demonstrated excellent or good Robinson scores in
      86.2% of patients and Odom scores in 87% of patients. Despite mostly excellent to
      good outcomes, symptomatic ASD is common after ACF. Although congenital stenosis
      appears to increase the incidence of radiographic ASD, it does not appear to
      predict symptomatic ASD. 

PMID- 24093700
TI  - Morphological characteristics of posterolateral articular fragments in tibial
      plateau fractures.
AB  - Treatment of posterolateral tibial plateau fractures is controversial, and
      information regarding this specific fracture pattern is lacking. The purpose of
      this study was to elucidate the frequency and morphological features of
      posterolateral articular fragments in tibial plateau fractures. A retrospective
      radiographic and chart review was performed on a consecutive series of patients
      who sustained tibial plateau fractures between May 2008 and August 2012. The
      articular surface area, maximum posterior cortical height, sagittal fracture
      angle, and amount of displacement were measured on computed tomography scans
      using the Picture and Archiving Communication System. Thirty-six (15%) of 242
      injuries demonstrated a posterolateral fracture fragment comprising a mean 14.3%
      of the articular surface of the total tibial plateau (range, 8% to 32%). Mean
      major articular fragment angle was 23 degrees  (range, 62 degrees  to -43 degrees
      ), mean maximum posterior cortical height was 29 mm (range, 18 to 42 mm), and
      mean sagittal fracture angle was 77 degrees  (range, 58 degrees  to 97 degrees ).
      The posterolateral plateau articular fracture fragment has morphological
      characteristics of a conically shaped fragment with a relatively small articular
      surface area and sagittal fracture angle. Recognizing these morphological
      features will help the clinician formulate an effective surgical plan. 

PMID- 24093701
TI  - Locking versus nonlocking construct in an osteoporotic, segmental fibula defect
      model.
AB  - Early studies on the treatment of osteoporotic distal fibular fractures suggest
      that poor bone quality can compromise fixation and, therefore, clinical outcome.
      Multiple prior biomechanical studies evaluated length-stable fracture models with
      destructive load-to-failure protocols, which may not represent a clinically
      relevant failure mode. The current authors compared a lateral locked construct
      with 2 distinct nonlocked constructs in an osteoporotic, segmental fibula defect
      model. Eighteen adult cadaveric ankles were randomized to a one-third tubular
      plate with nonlocking screws, a precontoured fibular plate with nonlocking
      screws, or the same pre-contoured plate with locking screws. Each was
      nondestructively loaded with an external rotation of 2.5 Nm for 10,000 cycles.
      The primary outcome was the change in construct stiffness. Secondary outcomes
      included maximal rotational displacement and change in insertion torques. Average
      increase in stiffness of the one-third tubular plate was 0.35 Nm/degree (P<.001),
      which was significantly greater than that in the nonlocking and locking
      precontoured plates (0.15 and 0.17 Nm/degree, respectively; P=.69). All 3
      constructs externally rotated to 11.7 degrees +/-4.6 degrees , 8.6 degrees +/-3.6
      degrees , and 10.9 degrees +/-4.7 degrees , respectively (P=.50). Average loss of
      insertion torque in the 4 proximal positions was 32.7%+/-19%, 41.3%+/-20.2%,
      57.8%+/-19%, and 64.9%+/-29.2% (P>.05). Average loss in the 4 distal positions
      for nonlocking constructs (71.6%+/-21%, 70.4%+/-26.4%, 93.1%+/-11%, and 83.3%+/
      35.4%) was significantly different from that for the locking construct (15%+/
      21.4%, 11.7%+/-24%, 9.2%+/-9.2%, and 20.8%+/-23.3%) (P<.05). No evidence in the
      current study supports the use of a locking plate for osteoporotic specimens. 

PMID- 24093702
TI  - BASK presentations: progress to journal publication.
AB  - Scientific conferences, such as the British Association for Surgery of the Knee
      (BASK) annual meeting, provide an important channel for the exchange of
      information between researchers. However, the ultimate means of disseminating
      research information is publication in a relevant peer-reviewed journal. The goal
      of this study was to follow up published abstracts in the Journal of Bone and
      Joint Surgery, British Volume supplement from the annual BASK conference and
      determine how many presented abstracts progressed to article publication in a
      peer-reviewed journal. Combined Google Scholar and PubMed searches of 602 BASK
      abstract titles over a 10-year period were performed, and the resulting articles
      were reviewed to confirm that they were directly associated with the
      corresponding abstracts. Two hundred (33.2%) abstracts presented at BASK
      conferences over a 10-year period were found in online or print format. This
      amount is comparable with other similar conferences' publication rates. Only one
      third of abstracts presented at the BASK conference were converted to journal
      publication as full articles. This may be due to multiple rejections, lack of
      time, relocation of the authors, or a reluctance to publish negative findings.
      Alternatively, changes in an abstract's title for publication prevents online
      search engines from identifying the final article and may explain some disparity.
      Furthermore, presented abstracts may not survive the strict peer-review process
      required for journal publication. Because these findings from BASK mirror other
      specialty meetings, clinicians should accept the results of orthopedic meeting
      proceedings with some level of caution. 

PMID- 24093703
TI  - Effect of health insurance type on access to care.
AB  - Growing orthopedic and nonorthopedic literature illustrates the point that having
      health insurance does not equal having access to care. The goal of this study was
      to evaluate the burden placed on patients to gain access to outpatient orthopedic
      care. For this study, burden was quantified as the distance traveled by the
      patient to be seen in clinic. This study was a retrospective review of all new
      patient encounters at an adult orthopedic outpatient clinic in an academic
      tertiary referral center over 1 calendar year. All patients were stratified into
      4 categories: commercial/private insurance, Medic-aid, Medicare, and
      uninsured/private pay. The average distance traveled by each patient to the
      center was then calculated based on the patient's billing zip code. Patient
      visits were further stratified based on whether the patients were seen by 1 of 3
      different categories of providers: general orthopedics/adult reconstruction,
      spine, and sports/upper extremity. The study group comprised 774 (31.1%) Medicaid
      patients, 653 (26.2%) Medicare patients, 917 (36.8%) commercial/private insurance
      patients, and 146 (5.9%) uninsured/private pay patients. The average 1-way
      distance traveled was 36.2 miles for Medicaid patients, 21.3 miles for Medicare
      patients, 24.1 miles for commercial/private insurance patients, and 25.3 miles
      for uninsured/private pay patients (P<.00). Subgroup analysis noted a statistical
      difference in distance traveled for the general orthopedics/adult reconstruction
      and sports/upper extremity groups. The study's findings suggest that having
      insurance does not equal access to outpatient orthopedic care at a single
      institution. The specific burdens that each group faces to gain access to care
      are unclear. 

PMID- 24093704
TI  - Changes in surgical procedures for acromioclavicular joint dislocation over the
      past 30 years.
AB  - Generally, surgical treatment is recommended for Rockwood type 5 traumatic
      acromioclavicular joint dislocations. Since 1980, the authors have performed the
      modified Dewar procedure, the modified Cadenat procedure, and anatomical
      reconstruction of the coracoclavicular ligaments for this injury. The goal of
      this study was to determine the ideal surgical procedure for acromioclavicular
      joint dislocations by comparing these 3 procedures. The modified Dewar procedure
      was performed on 55 patients (Dewar group), the modified Cadenat procedure was
      performed on 73 patients (Cadenat group), and anatomical reconstruction of the
      coracoclavicular ligaments was performed on 11 patients (reconstruction group).
      According to the UCLA scoring system, therapeutic results averaged 27.3 points in
      the Dewar group, 28.2 in the Cadenat group, and 28.4 in the reconstruction group.
      The incidence of residual subluxation or dislocation in the acromioclavicular
      joint was evaluated at final radiographic follow-up. Subluxation occurred in 21
      patients in the Dewar group, 18 in the Cadenat group, and 3 in the reconstruction
      group. Dislocation occurred in 3 patients in the Dewar group. Osteoarthritic
      changes in the acromioclavicular joint occurred in 20 patients in the Dewar
      group, 9 in the Cadenat group, and 1 in the reconstruction group. The modified
      Cadenat procedure can provide satisfactory therapeutic results and avoid
      postoperative failure or loss of reduction compared with the modified Dewar
      procedure. However, the modified Cadenat procedure does not anatomically restore
      the coracoclavicular ligaments. Anatomic restoration of both coracoclavicular
      ligaments can best restore acromioclavicular joint function. 

PMID- 24093705
TI  - Role of serum lipoprotein at the site of iloprost therapy in the treatment of
      painful bone marrow edema.
AB  - The authors hypothesized that the emergence of painful bone marrow edema occurs
      through microembolisms in the bone marrow that may be reflected in elevated
      plasma parameters of hypofibrinolysis or a disturbance of the lipid metabolism
      and that treatment with iloprost may lead to a decrease in or normalization of
      the elevated serum parameters and, therefore, to pain reduction. Twenty-one
      patients (12 men and 9 women; mean age, 50 years [range, 22-70 years]) with
      painful bone marrow edema and elevated lipoprotein(a) (Lp[a]) serum values were
      treated with intravenous iloprost. Before and 6 weeks after iloprost therapy, the
      serum concentrations of Lp(a), apolipoprotein A1 (ApoA1), and apolipoprotein B
      (ApoB) were determined. At 6-week follow-up, 17 patients reported complete
      resolution of their symptoms. For these patients, complete bone marrow edema
      resolution was observed on magnetic resonance imaging. Four patients reported
      that their symptoms were either the same or had worsened but had partial bone
      marrow edema resolution on magnetic resonance imaging. In these patients, Lp(a)
      values either increased or remained the same. Hence, the total success rate of
      iloprost treatment was 86% at a mean follow-up of 17 months (range, 3-45 months).
      Before iloprost therapy, mean ApoA1, ApoB, and Lp(a) values were 159.8, 108.3,
      and 69.1 mg/dL, respectively. Six weeks after iloprost therapy, mean ApoA1, ApoB,
      and Lp(a) values decreased to 147.6 (P=.011), 98.4 (P=.042), and 38.3 (P<.001)
      mg/dL, respectively. The results of this study indicate a possible role of
      hypofibrinolysis or a disturbance in the lipid metabolism in the emergence of
      painful bone marrow edema. 

PMID- 24093706
TI  - Open versus percutaneous release for the treatment of trigger thumb.
AB  - The purpose of this retrospective study was to compare the outcomes and
      complications of conventional open surgical release and percutaneous needle
      release in the treatment of trigger thumb. The study comprised 87 patients with
      trigger thumb who were treated with either open pulley (n=52) or percutaneous
      (n=32) release between 2008 and 2011. All patients were reevaluated at a mean
      follow-up of 22.7+/-9.6 months (range, 9-44 months). Main outcome measures were
      the rate of recurrence, pain on movement or tenderness over the pulley, infection
      rate, digital nerve injury, tendon bowstringing, joint stiffness or loss of thumb
      range of motion, and patient satisfaction. The groups were statistically similar
      regarding age, sex, laterality, dominant side involvement, and trigger thumb
      grade on initial admission. At final follow-up, no patient had recurrence, tendon
      bowstringing, joint stiffness, or loss of thumb range of motion. No patients in
      the open pulley release group and 2 (5.7%) patients in the percutaneous release
      group had a digital nerve injury (P=.159). No statistical difference was found in
      the infection rate between groups (P=.354). A total of 98.1% of patients in the
      open pulley release group and 97.1% of patients in the percutaneous release group
      were satisfied with treatment (P=.646). Both techniques resulted in similar
      therapeutic efficacy, and the rate of potential complications was also
      statistically similar in each group. Although statistically insignificant, the
      authors believe that the 5.7% rate of iatrogenic digital nerve injury seen in the
      percutaneous release group is clinically significant and serious. Therefore, they
      advocate using open surgical release of trigger thumb. 

PMID- 24093707
TI  - Anatomy and histology of the transverse humeral ligament.
AB  - The classic literature describes the transverse humeral ligament (THL) as a
      distinct anatomic structure with a role in biceps tendon stability; however,
      recent literature suggests that it is not a distinct anatomic structure. The
      purpose of this study was to evaluate the gross and microscopic anatomy of the
      THL, including a specific investigation of the histology of this ligament. Thirty
      frozen, embalmed cadaveric specimens were dissected to determine the gross
      anatomy of the THL. Seven specimens were evaluated histologically for the
      presence of mechanoreceptors and free nerve endings. Two tissue layers were
      identified in the area described as the THL. In the deep layer, fibers of the
      subscapularis tendon were found to span the bicipital groove with contributions
      from the coracohumeral ligament and the supraspinatus tendon. Superficial to this
      layer was a fibrous fascial covering consisting of distinct bands of tissue.
      Neurohistology staining revealed the presence of free nerve endings but no
      mechanoreceptors. This study's findings demonstrate that the THL is a distinct
      structure continuous with the rotator cuff tendons and the coracohumeral
      ligament. The finding of free nerve endings in the THL suggests a potential role
      as a shoulder pain generator. 

PMID- 24093708
TI  - Endo-Modell rotating-hinge total knee for revision total knee arthroplasty.
AB  - The goal of this study was to analyze the clinical and radiographic results and
      the survival rate of a series of rotating-hinge implants used for revision total
      knee arthroplasties in mild and severe instability. Between December 1991 and
      June 2004, fifty-three revision total knee arthroplasties were performed using
      the Endo-Modell (Waldemar LINK GmbH and Co, Hamburg, Germany) rotating-hinge
      prosthesis; 7 (13.2%) patients underwent partial revision of a previous Endo
      Modell. All patients were evaluated preoperatively, 3 and 6 months
      postoperatively, and annually thereafter using the Hospital for Special Surgery
      (HSS) knee score and the Knee Society Roentgenographic Evaluation System (KS
      RES). Mean follow-up was 155.2+/-40.1 months (range, 78-240 months), with 32
      patients examined at the final follow-up. All HSS knee scores increased from
      preoperatively to last follow-up. No statistically significance differences were
      found in the HSS knee scores between septic and aseptic revisions and between
      total or partial revisions. Progressive radiolucent lines were detected in 8
      (25%) patients. Implant failure occurred in 11 (20.7%) patients; the cumulative
      survival of the implants was 80.4% at 150 months for the final 32 patients. The
      authors recommend use of this implant for revision total knee arthroplasty,
      especially in patients with severe instability and bone loss. 

PMID- 24093709
TI  - Randomized, controlled trial of the modified Stoppa versus the ilioinguinal
      approach for acetabular fractures.
AB  - The objective of this study was to determine whether the modified Stoppa approach
      or the ilioinguinal approach is better for the treatment of acetabular fractures
      by comparing the results of those 2 approaches. A randomized trial was undertaken
      of 60 consecutive patients with acetabular fractures treated with either the
      modified Stoppa or the ilioinguinal approach. In addition to the patients'
      demographics, the assessed preoperative parameters included fracture pattern,
      associated injuries, time to surgery, and Injury Severity Score; intraoperative
      parameters included blood loss and operative time for each procedure; and
      postoperative parameters included wound drainage, blood transfusion,
      perioperative complications, early operative complications, late operative
      complications, quality of reduction, radiological results, and clinical outcomes.
      The study showed no significant differences in all measured preoperative
      variables between the 2 groups (all P>.05). In addition, no significant
      differences were found in the intraoperative complication rate, early operative
      complication rate, late operative complication rate, quality of reduction,
      radiological results, and clinical outcomes (all P>.05). However, compared with
      the ilioinguinal approach, the modified Stoppa approach reduced intraoperative
      blood loss-and in doing so decreased wound drainage and the need for blood
      transfusion-and shortened operative time (all P<.05). The authors recommend using
      the modified Stoppa approach rather than the classical ilioinguinal approach to
      treat acetabular fractures when anterior exposure of the acetabulum is required. 

PMID- 24093710
TI  - Biomechanical comparison of axial load between cannulated locking screws and
      noncannulated cortical locking screws.
AB  - The goal of this study was to compare the biomechanical stability of cannulated
      locking screws and noncannulated cortical locking screws in a periarticular
      locking plate. Twelve fresh-frozen porcine tibias with a 1-cm gap created distal
      to the tibial plateau were used to simulate an unstable proximal tibial fracture.
      All specimens were fixed with a periarticular proximal lateral tibial locking
      plate and divided into 2 groups based on whether the proximal metaphyseal screw
      holes of the plate were inserted with either cannulated locking screws or
      noncannulated cortical locking screws. An axial compressive load was applied to
      cause failure in each specimen using a materials testing instrument. The axial
      stiffness and maximum failure strength in axial loading were recorded. Axial
      stiffness of the constructs using noncannulated cortical locking screw was
      significantly higher than that of the constructs using cannulated locking screws
      (P=.006). Axial failure strength of the constructs using noncannulated cortical
      locking screw was significantly higher than that of the constructs using
      cannulated locking screws (P=.002). The failure mode observed in all specimens
      was a permanent screw-bending deformity over the head-shaft junction of proximal
      metaphyseal screws, irrespective of whether they were cannulated or noncannulated
      cortical locking screws. Fixation with noncannulated cortical locking screws
      offered more stability than cannulated locking screws with regard to axial
      stiffness and failure strength in a porcine model with unstable proximal tibial
      fractures. 

PMID- 24093712
TI  - Unique failure mechanism of a femoral component after revision total hip
      arthroplasty.
AB  - As the prevalence of revision total hip arthroplasty increases, the mechanisms of
      failure of these revisions have become better delineated. Several studies have
      indicated infection, instability, and aseptic loosening to be the more common
      mechanisms of failure in revision surgery. However, with increasing numbers of
      revisions performed, unique mechanisms of failure are being seen, likely related
      to the implants that are used in the revision setting. Revision implants offer
      certain advantages over primary implants with the use of modular components. The
      revision implants allow the surgeon to increase offset and leg length with
      modular femoral bodies and necks. However, these modular junctions represent
      additional areas for implant failure. These new methods of failure associated
      with modular implants are slowly presenting as the use of these implants
      continues to increase. The authors recently encountered a mechanism of failure
      that, to their knowledge, has not been described in the literature. They report a
      57-year-old man with dissociation of the proximal body from the diaphyseal
      component of a Wright Medical Link (Memphis, Tennessee) stem prosthesis. The
      patient presented with an audible click on physical examination, and radiographs
      confirmed dissociation of the proximal body. The intraoperative findings,
      treatment method, and proposed mechanisms for this type of failure are presented,
      as well as insight into potential ways to avoid this type of failure. 

PMID- 24093711
TI  - Effectiveness of local tenoxicam versus corticosteroid injection for plantar
      fasciitis treatment.
AB  - Plantar fasciitis is one of the most common causes of foot pain in adults. In
      this prospective study, the outcomes of local tenoxicam injection and
      corticosteroid therapy for the treatment of plantar fasciitis were compared.
      Patients were randomly assigned to either the tenoxicam or corticosteroid group.
      The tenoxicam group (n=31) was treated using a local injection of 1 mL of
      tenoxicam (20 mg/2 mL) and 1 mL of 2% lidocaine, whereas the steroid group (n=30)
      was treated with a local 1-mL injection containing 40 mg of methylprednisolone
      acetate and 1 mL of 2% lidocaine. Clinical evaluations, which were performed
      before the injection and 6 and 12 months after the injection, consisted of
      patient-assessed pain using a visual analog scale. In addition, patient
      satisfaction was measured using the Roles and Maudsley score. Comparison of pre-
      and posttreatment visual analog scale scores demonstrated a statistically
      significant difference in both groups (P<.05). Furthermore, no significant
      difference was found between the steroid and tenoxicam groups in terms of visual
      analog scale scores measured 12 months after injection (P>.05). The tenoxicam
      injection was not significantly more effective than the corticosteroid injection.
      However, both methods were effective and successful in treating patients with
      plantar fasciitis. Tenoxicam therapy appears to provide pain relief, but its
      effectiveness in the long term should be explored in additional studies. 

PMID- 24093713
TI  - Anterior interosseous nerve palsy as a complication of proximal humerus fracture.
AB  - Anterior interosseous nerve palsy subsequent to proximal humerus fracture is rare
      compared with an axillary nerve injury. This article presents a case of anterior
      interosseous nerve palsy secondary to such a fracture in an 87-year-old woman
      after a simple fall onto her outstretched hand. The patient had no sensory
      involvement but was unable to form an O with her thumb and index finger. She had
      a positive pointing index test on attempting to clasp her hand. The fracture and
      nerve palsy were treated conservatively. At 3-month follow-up, the patient had
      partial recovery; therefore, electromyography was not performed. By 6 months, she
      had complete recovery of anterior interosseous nerve palsy. This case highlights
      the possibility of sustaining anterior interosseous nerve palsy with proximal
      humerus fracture with a classical clinical presentation. Because most nerve
      lesions after proximal humerus fracture are neurapraxia, symptoms usually resolve
      either partially or completely after a few months. It is recommended that cases
      with proximal humerus fracture be evaluated carefully for median nerve and
      axillary nerve injury. In addition, it is recommended to perform electromyography
      if no signs of recovery are evident at 3-month follow-up. 

PMID- 24093714
TI  - Dislocated double-layered lateral meniscus mimicking the bucket-handle tear.
AB  - Various shapes of congenital abnormalities of the meniscus have been reported.
      Among them, the double-layered meniscus is rare. This article describes a 22-year
      old man with a double-layered lateral meniscus who reported right knee pain with
      no history of trauma. The double-layered lateral meniscus included both the upper
      and lower meniscus. The anterior and posterior edge of the upper meniscus was
      attached to the lower lateral meniscus, and its periphery was not connected to
      the capsule and the lower meniscus. In addition, the upper meniscus was
      dislocated into the intercondylar notch, mimicking a bucket-handle tear. However,
      the lower meniscus was normal in appearance, so a bucket-handle or horizontal
      tear of the meniscus was ruled out of the differential diagnosis. Although this
      is a rare case, clinicians should be aware of this anomaly due to the potential
      for a double-layered meniscus to contribute to a bucket-handle or horizontal tear
      of the lower meniscus. Therefore, early diagnosis and proper treatment of a
      double-layered meniscus are needed before an additional injury occurs to a normal
      meniscus. 

PMID- 24093716
TI  - Antioxidant and antidiarrheal activities of ethanol extract of Ardisia elliptica
      fruits.
AB  - CONTEXT: Ardisia elliptica Thunb Lam. (Myrsinaceae) is widely used traditionally
      in the treatment of diarrhea related health disorders in Bangladesh. OBJECTIVE:
      The crude ethanol extract of Ardisia elliptica fruits (EFA) was evaluated for its
      antioxidant and antidiarrhoeal activities. MATERIALS AND METHODS: DPPH radical
      scavenging, nitric oxide scavenging, reducing power and Fe(++) ion chelating
      ability were used for determining antioxidant activities and animal models were
      used for antidiarrheal activities such as the castor oil and magnesium sulfate
      induced diarrhea, enteropooling induced by the administration of castor oil and
      magnesium sulfate at the doses of 250 and 500 mg/kg. RESULTS: The extract
      possessed a significant DPPH free radical scavenging activity with an IC50 value
      of 30.75 MUg/ml compared to ascorbic acid (IC50: 7.89 MUg/ml). The IC50 values of
      the extract and ascorbic acid were 51.72 and 38.68 MUg/ml, respectively, in
      nitric oxide scavenging assay. The IC50 value of the extract for Fe(++) ion
      chelating ability (41.30 MUg/ml) was also found to be significant compared to the
      IC50 value of EDTA (22.57 MUg/ml). The EFA also showed a significant protection
      (p < 0.001) against experimentally induced diarrhea by castor oil and magnesium
      sulfate as evidenced by a decrease in the number of defecation with respect to
      control. The diarrhea induced by castor oil and magnesium sulfate enteropooling
      was prevented by all the tested doses. CONCLUSION: Therefore, the obtained
      results confirm the antioxidant and antidiarrheal activity of EFA and thus
      support the traditional uses of this plant as a modality for antioxidant and
      antidiarrheal activity.

PMID- 24093715
TI  - Depressive symptoms, self-esteem, HIV symptom management self-efficacy and self
      compassion in people living with HIV.
AB  - The aims of this study were to examine differences in self-schemas between
      persons living with HIV/AIDS with and without depressive symptoms, and the degree
      to which these self-schemas predict depressive symptoms in this population. Self
      schemas are beliefs about oneself and include self-esteem, HIV symptom management
      self-efficacy, and self-compassion. Beck's cognitive theory of depression guided
      the analysis of data from a sample of 1766 PLHIV from the USA and Puerto Rico.
      Sixty-five percent of the sample reported depressive symptoms. These symptoms
      were significantly (p <= 0.05), negatively correlated with age (r = -0.154),
      education (r = -0.106), work status (r = -0.132), income adequacy (r = -0.204,
      self-esteem (r = -0.617), HIV symptom self-efficacy (r = - 0.408), and self
      kindness (r = - 0.284); they were significantly, positively correlated with
      gender (female/transgender) (r = 0.061), white or Hispanic race/ethnicity (r =
      0.047) and self-judgment (r = 0.600). Fifty-one percent of the variance (F =
      177.530 (df = 1524); p < 0.001) in depressive symptoms was predicted by the
      combination of age, education, work status, income adequacy, self-esteem, HIV
      symptom self-efficacy, and self-judgment. The strongest predictor of depressive
      symptoms was self-judgment. Results lend support to Beck's theory that those with
      negative self-schemas are more vulnerable to depression and suggest that
      clinicians should evaluate PLHIV for negative self-schemas. Tailored
      interventions for the treatment of depressive symptoms in PLHIV should be tested
      and future studies should evaluate whether alterations in negative self-schemas
      are the mechanism of action of these interventions and establish causality in the
      treatment of depressive symptoms in PLHIV.

PMID- 24093717
TI  - Biomimetic-engineered poly (ethylene glycol) hydrogel for smooth muscle cell
      migration.
AB  - We report on a biomimetic scaffold as a model system to evaluate smooth muscle
      cell (SMC) migration in three dimensions. To accomplish this, bio-inert poly
      (ethylene glycol) (PEG)-based hydrogels were designed as the scaffold substrate.
      To mimic properties of the extracellular matrix, cell-adhesive peptide (GRGDSP)
      derived from fibronectin and collagenase-sensitive peptide (GPQGIAGQ) derived
      from collagen type I were incorporated into the PEG macromer chain.
      Copolymerization of the biomimetic macromers results in the formation of
      bioactive PEG hydrogels with cell adhesivity and biodegradability. By utilizing
      these biomimetic scaffolds, we studied the effect of adhesive ligand
      concentration, proteolysis, and network cross-linking density on cell migration.
      Our results showed that three-dimensional SMC migration has a biphasic dependence
      on adhesive ligand density, and both adhesive and collagenase-sensitive peptides
      were required for cell migration to occur. Furthermore, network cross-linking
      density was shown to dramatically influence the behavior of cell migration in the
      hydrogels. 

PMID- 24093718
TI  - The bZIP protein from Tamarix hispida, ThbZIP1, is ACGT elements binding factor
      that enhances abiotic stress signaling in transgenic Arabidopsis.
AB  - BACKGROUND: Tamarix spp. are woody halophyte, which are very tolerant to abiotic
      stresses such as salinity and drought, but little is known about their specific
      stress response systems. Basic leucine zipper proteins (bZIPs) play important
      roles in the ability of plants to withstand adverse environmental conditions.
      However, their exact roles in abiotic stress tolerance are still not fully known.
      In the current study, we functionally characterized a bZIP gene (ThbZIP1) from
      Tamarix hispida in response to abiotic stresses. RESULTS: We addressed the
      regulatory network of ThbZIP1 in three levels, i.e. its upstream regulators, the
      cis-acting elements recognized by ThbZIP1, and its downstream target genes. Two
      MYCs were found to bind to E-box, in the promoter of ThbZIP1 to activate its
      expression. Expression of ThbZIP1 is induced by ABA, salt, drought, methyl
      viologen and cold. ThbZIP1 can specifically bind to ACGT elements, with the
      highest binding affinity to the C-box, followed by the G-box and lastly the A
      box. Compared with wild-type (Col-0) Arabidopsis, transgenic plants expressing
      ThbZIP1 had an increased tolerance to drought and salt, but had an increased
      sensitivity to ABA during seed germination and root growth; meanwhile, ROS level,
      cell death and water loss rate in transgenic plants were significantly reduced.
      Microarray analyses showed that many ROS scavenging genes were up-regulated by
      ThbZIP1 under salt stress conditions. CONCLUSIONS: Based on these data, we
      suggest that ThbZIP1 confers abiotic stress tolerance through activating stress
      tolerance genes to modulate ROS scavenging ability and other physiological
      changes involved in stress tolerance, and plays an important role in the ABA
      mediated stress response of T. hispida.

PMID- 24093719
TI  - No agenda.

PMID- 24093720
TI  - Dying revisited: understanding the process, six years later.

PMID- 24093721
TI  - Association between hospice care and psychological outcomes in Alzheimer's
      spousal caregivers.
AB  - CONTEXT: Dementia care giving can lead to increased stress, physical and
      psychosocial morbidity, and mortality. Anecdotal evidence suggests that hospice
      care provided to people with dementia and their caregivers may buffer caregivers
      from some of the adverse outcomes associated with family caregiving in
      Alzheimer's Disease (AD). OBJECTIVES: This pilot study examined psychological and
      physical outcomes among 32 spousal caregivers of patients with AD. It was
      hypothesized that caregivers who utilized hospice services would demonstrate
      better outcomes after the death of their spouse than caregivers who did not
      utilize hospice. METHODS: The charts of all spousal caregivers enrolled in a
      larger longitudinal study from 2001 to 2006 (N=120) were reviewed, and
      participants whose spouse had died were identified. Of these, those who received
      hospice care (n=10) were compared to those who did not (n=22) for various
      physiological and psychological measures of stress, both before and after the
      death of the care recipient. An Analysis of Covariance (ANCOVA), with postdeath
      scores as the dependent variable and pre-death scores as covariates, was used for
      all variables. RESULTS: Significant group differences were found in postdeath
      depressive symptoms (HAM-D; F(1,29)=6.10, p<0.05) and anxiety symptoms (HAM-A;
      F(1,29)=5.71, p<0.05). Most psychological outcome variables demonstrated moderate
      effect sizes with a Cohen's d of>0.5 between groups. CONCLUSIONS: These data
      suggest that hospice enrollment may ameliorate the detrimental psychological
      effects in caregivers who have lost a spouse with Alzheimer's Disease. Based on
      these pilot data, further prospective investigation is warranted.

PMID- 24093722
TI  - Biological therapies for the treatment of cutaneous wounds: phase III and
      launched therapies.
AB  - INTRODUCTION: Normal wound healing mechanisms can be overwhelmed in the setting
      of complex acute and chronic tissue injury. Biological therapies are designed to
      augment and/or restore the body's natural wound healing abilities. There are a
      variety of available and emerging technologies utilizing this approach that have
      demonstrated the ability to augment wound healing. AREAS COVERED: In this review,
      the clinical data on launched and emerging biological therapies for wound healing
      applications are summarized. The methodologies discussed include biological skin
      equivalents, growth factors/small molecules and stem cell-based therapies. EXPERT
      OPINION: While many products possess convincing clinical data demonstrating their
      efficacy in comparison to standard treatment options, more robust, controlled
      studies are needed to determine the relative value among established and emerging
      biological therapies. Future bioengineering and stem cell-based approaches are of
      particular interest due to the simultaneous correction of multiple deficiencies
      present in the nonhealing wound.

PMID- 24093723
TI  - The Gene Ontology (GO) Cellular Component Ontology: integration with SAO
      (Subcellular Anatomy Ontology) and other recent developments.
AB  - BACKGROUND: The Gene Ontology (GO) (http://www.geneontology.org/) contains a set
      of terms for describing the activity and actions of gene products across all
      kingdoms of life. Each of these activities is executed in a location within a
      cell or in the vicinity of a cell. In order to capture this context, the GO
      includes a sub-ontology called the Cellular Component (CC) ontology (GO-CCO). The
      primary use of this ontology is for GO annotation, but it has also been used for
      phenotype annotation, and for the annotation of images. Another ontology with
      similar scope to the GO-CCO is the Subcellular Anatomy Ontology (SAO), part of
      the Neuroscience Information Framework Standard (NIFSTD) suite of ontologies. The
      SAO also covers cell components, but in the domain of neuroscience. DESCRIPTION:
      Recently, the GO-CCO was enriched in content and links to the Biological Process
      and Molecular Function branches of GO as well as to other ontologies. This was
      achieved in several ways. We carried out an amalgamation of SAO terms with GO-CCO
      ones; as a result, nearly 100 new neuroscience-related terms were added to the
      GO. The GO-CCO also contains relationships to GO Biological Process and Molecular
      Function terms, as well as connecting to external ontologies such as the Cell
      Ontology (CL). Terms representing protein complexes in the Protein Ontology (PRO)
      reference GO-CCO terms for their species-generic counterparts. GO-CCO terms can
      also be used to search a variety of databases. CONCLUSIONS: In this publication
      we provide an overview of the GO-CCO, its overall design, and some recent
      extensions that make use of additional spatial information. One of the most
      recent developments of the GO-CCO was the merging in of the SAO, resulting in a
      single unified ontology designed to serve the needs of GO annotators as well as
      the specific needs of the neuroscience community.

PMID- 24093724
TI  - Hypoxia-induced inhibition of epithelial Na(+) channels in the lung. Role of
      Nedd4-2 and the ubiquitin-proteasome pathway.
AB  - Transepithelial sodium transport via alveolar epithelial Na(+) channels (ENaC)
      and Na(+),K(+)-ATPase constitutes the driving force for removal of alveolar edema
      fluid. Alveolar hypoxia associated with pulmonary edema may impair ENaC activity
      and alveolar Na(+) absorption through a decrease of ENaC subunit expression at
      the apical membrane of alveolar epithelial cells (AECs). Here, we investigated
      the mechanism(s) involved in this process in vivo in the beta-Liddle mouse strain
      mice carrying a truncation of beta-ENaC C-terminus abolishing the interaction
      between beta-ENaC and the ubiquitin protein-ligase Nedd4-2 that targets the
      channel for endocytosis and degradation and in vitro in rat AECs. Hypoxia (8% O2
      for 24 h) reduced amiloride-sensitive alveolar fluid clearance by 69% in wild
      type mice but had no effect in homozygous mutated beta-Liddle littermates. In
      vitro, acute exposure of AECs to hypoxia (0.5-3% O2 for 1-6 h) rapidly decreased
      transepithelial Na(+) transport as assessed by equivalent short-circuit current
      Ieq and the amiloride-sensitive component of Na(+) current across the apical
      membrane, reflecting ENaC activity. Hypoxia induced a decrease of ENaC subunit
      expression in the apical membrane of AECs with no change in intracellular
      expression and induced a 2-fold increase in alpha-ENaC polyubiquitination.
      Hypoxic inhibition of amiloride-sensitive Ieq was fully prevented by
      preincubation with the proteasome inhibitors MG132 and lactacystin or with the
      antioxidant N-acetyl-cysteine. Our data strongly suggest that Nedd4-2-mediated
      ubiquitination of ENaC leading to endocytosis and degradation of apical Na(+)
      channels is a key feature of hypoxia-induced inhibition of transepithelial
      alveolar Na(+) transport. 

PMID- 24093725
TI  - Aberrant topographical organization in gray matter structural network in late
      life depression: a graph theoretical analysis.
AB  - BACKGROUND: Although previous studies on late life depression (LLD) have shown
      morphological abnormalities in frontal-striatal-temporal areas, alterations in
      coordinated patterns of structural brain networks in LLD are still poorly
      understood. The aim of this study was to investigate differences in gray matter
      structural brain network between LLD and healthy controls. METHODS: We used gray
      matter volume measurement from magnetic resonance imaging to investigate large
      scale structural brain networks in 37 LLD patients and 40 normal controls. Brain
      networks were constructed by thresholding gray matter volume correlation matrices
      of 90 regions and analyzed using graph theoretical approaches. RESULTS: Although
      both LLD and control groups showed a small-world organization of group networks,
      there were no differences in the clustering coefficient, the path length, and the
      small-world index across a wide range of network density. Compared with controls,
      LLD patients showed decreased nodal betweenness in the medial orbitofrontal and
      angular gyrus regions. In addition, LLD patients showed hub regions in superior
      temporal gyrus and middle cingulate gyrus, and putamen. On the other hand, the
      control group showed hub regions in the medial orbitofrontal gyrus, middle
      cingulate gyrus, and cuneus. CONCLUSION: Our findings suggest that the gray
      matter structural networks are not globally but regionally altered in LLD
      patients. This multivariate structural analysis using graph theory might provide
      a more appropriate paradigm for understanding complicated neurobiological
      mechanism of LLD.

PMID- 24093727
TI  - Impact of AlCl3 on the self-assembly of the anionic surfactant sodium
      polyethylene glycol monoalkyl ether sulfate in aqueous solution.
AB  - Small-angle neutron scattering has been used to study the self-assembly of the
      anionic surfactant sodium polyethylene glycol monoalkyl ether sulfate in aqueous
      solution and in the presence of Al(3+) multivalent counterions in the form of
      AlCl3. The addition of the Al(3+) ions promotes significant micellar growth of
      the initially globular micelles into highly elongated structures until ultimately
      lamellar structures form. Increasing the size of the polyethylene oxide, EO,
      group progressively suppresses micellar growth before lamellar formation.
      Reducing the alkyl chain length has a similar effect on the structural evolution.
      Both trends are associated with increased solubility with increasing EO group
      size and decreasing alkyl chain length. Both the size of the EO group and the
      length of the alkyl chain affect sodium diethylene glycol monododecyl ether
      sulfate/Al(3+) complex formation and drive lamellar formation to progressively
      higher AlCl3 concentrations. 

PMID- 24093726
TI  - Analysis of partial and complete protection in malaria cohort studies.
AB  - BACKGROUND: Malaria transmission is highly heterogeneous and analysis of
      incidence data must account for this for correct statistical inference. Less
      widely appreciated is the occurrence of a large number of zero counts (children
      without a malaria episode) in malaria cohort studies. Zero-inflated regression
      methods provide one means of addressing this issue, and also allow risk factors
      providing complete and partial protection to be disentangled. METHODS: Poisson,
      negative binomial (NB), zero-inflated Poisson (ZIP) and zero-inflated negative
      binomial (ZINB) regression models were fitted to data from two cohort studies of
      malaria in children in Ghana. Multivariate models were used to understand risk
      factors for elevated incidence of malaria and for remaining malaria-free, and to
      estimate the fraction of the population not at risk of malaria. RESULTS: ZINB
      models, which account for both heterogeneity in individual risk and an unexposed
      sub-group within the population, provided the best fit to data in both cohorts.
      These approaches gave additional insight into the mechanism of factors
      influencing the incidence of malaria compared to simpler approaches, such as NB
      regression. For example, compared to urban areas, rural residence was found to
      both increase the incidence rate of malaria among exposed children, and increase
      the probability of being exposed. In Navrongo, 34% of urban residents were
      estimated to be at no risk, compared to 3% of rural residents. In Kintampo, 47%
      of urban residents and 13% of rural residents were estimated to be at no risk.
      CONCLUSION: These results illustrate the utility of zero-inflated regression
      methods for analysis of malaria cohort data that include a large number of zero
      counts. Specifically, these results suggest that interventions that reach mainly
      urban residents will have limited overall impact, since some urban residents are
      essentially at no risk, even in areas of high endemicity, such as in Ghana.

PMID- 24093728
TI  - Intramolecular transannulation of alkynyl triazoles via alkyne-carbene metathesis
      step: access to fused pyrroles.
AB  - An intramolecular Rh-catalyzed transannulation reaction of alkynyl triazoles has
      been developed. This method allows efficient construction of various 5,5-fused
      pyrroles, including tetrahydropyrrolo and spiro systems. The method demonstrates
      excellent functional group compatibility. A rhodium carbene-alkyne metathesis
      mechanism is proposed for this transformation. 

PMID- 24093729
TI  - afterParty: turning raw transcriptomes into permanent resources.
AB  - BACKGROUND: Next-generation DNA sequencing technologies have made it possible to
      generate transcriptome data for novel organisms quickly and cheaply, to the
      extent that the effort required to annotate and publish a new transcriptome is
      greater than the effort required to sequence it. Often, following publication,
      details of the annotation effort are only available in summary form, hindering
      subsequent exploitation of the data. To promote best-practice in annotation and
      to ensure that data remain accessible, we have written afterParty, a web
      application that allows users to assemble, annotate and publish novel
      transcriptomes using only a web browser. RESULTS: afterParty is a robust web
      application that implements best-practice transcriptome assembly, annotation,
      browsing, searching, and visualization. Users can turn a collection of reads
      (from Roche 454 chemistry) or assembled contigs (from any sequencing chemistry,
      including Illumina Solexa RNA-Seq) into a searchable, browsable transcriptome
      resource and quickly make it publicly available. Contigs are functionally
      annotated based on similarity to known sequences and protein domains. Once
      assembled and annotated, transcriptomes derived from multiple species or
      libraries can be compared and searched. afterParty datasets can either be created
      using the existing afterParty server, or using local instances that can be built
      easily using a virtual machine. afterParty includes powerful visualization tools
      for transcriptome dataset exploration and uses a flexible annotation architecture
      which will allow additional types of annotation to be added in the future.
      CONCLUSIONS: afterParty's main use case scenario is one in which a working
      biologist has generated a large volume of transcribed sequence data and wishes to
      turn it into a useful resource that has some durability. By reducing the effort,
      bioinformatics skills, and computational resources needed to annotate and publish
      a transcriptome, afterParty will facilitate the annotation and sharing of
      sequence data that would otherwise remain unavailable. A typical metazoan
      transcriptome containing several tens of thousands of contigs can be annotated in
      a few minutes of interactive time and a few days of computational time.

PMID- 24093730
TI  - Iron cycling at corroding carbon steel surfaces.
AB  - Surfaces of carbon steel (CS) exposed to mixed cultures of iron-oxidizing
      bacteria (FeOB) and dissimilatory iron-reducing bacteria (FeRB) in seawater media
      under aerobic conditions were rougher than surfaces of CS exposed to pure
      cultures of either type of microorganism. The roughened surface, demonstrated by
      profilometry, is an indication of loss of metal from the surface. In the presence
      of CS, aerobically grown FeOB produced tight, twisted helical stalks encrusted
      with iron oxides. When CS was exposed anaerobically in the presence of FeRB, some
      surface oxides were removed. However, when the same FeOB and FeRB were grown
      together in an aerobic medium, FeOB stalks were less encrusted with iron oxides
      and appeared less tightly coiled. These observations suggest that iron oxides on
      the stalks were reduced and solubilized by the FeRB. Roughened surfaces of CS and
      denuded stalks were replicated with culture combinations of different species of
      FeOB and FeRB under three experimental conditions. Measurements of
      electrochemical polarization resistance established different rates of corrosion
      of CS in aerobic and anaerobic media, but could not differentiate rate
      differences between sterile controls and inoculated exposures for a given bulk
      concentration of dissolved oxygen. Similarly, total iron in the electrolyte could
      not be used to differentiate treatments. The experiments demonstrate the
      potential for iron cycling (oxidation and reduction) on corroding CS in aerobic
      seawater media. 

PMID- 24093734
TI  - 'Temari Reiki: a new hands-off approach to traditional Reiki'.

PMID- 24093733
TI  - Serial analysis of clinical and imaging indices reveals prolonged efficacy of TNF
      alpha and IL-6 receptor targeted therapies in refractory Takayasu arteritis.
AB  - OBJECTIVES: We analysed a large cohort of patients with Takayasu arteritis,
      seeking robust clinical evidence for prolonged responses to tumour necrosis
      factor-alpha (TNF-alpha) and interleukin-6 receptor (IL-6R) antagonists in severe
      refractory disease. METHODS: Case notes from ninety-eight patients with Takayasu
      arteritis were retrospectively reviewed. Drug treatment, laboratory and serial
      non-invasive imaging data were analysed, and the Indian Takayasu arteritis
      activity (ITAS) and damage scores (TADs) calculated. RESULTS: Nine patients were
      treated with biologic therapies. All had previously received high dose
      prednisolone and >=1 conventional immunosuppressant. Five patients had failed
      cyclophosphamide. The patients prescribed biologics had more extensive arterial
      injury than the remainder of the cohort and persistent active disease (ITAS range
      2-9, CRP 12-206 mg/L, TADs 3--1). Eight patients were prescribed anti-TNF-alpha
      therapy, three IL-6R blockade. The mean duration of anti-TNF-alpha treatment was
      42 months (maximum 8 years). One patient developed new arterial stenoses while
      receiving anti-TNF-alpha and subsequently achieved disease remission with
      tocilizumab. Two patients have now demonstrated sustained responses to IL-6R
      inhibition at 19 and 20 months. Following introduction of biologic therapy,
      serial non-invasive imaging has revealed no significant progression in arterial
      injury. A significant fall in CRP (p<0.01), prednisolone dose (p<0.01) and ITAS
      (p<0.01) was observed, with no increase in TADs. CONCLUSIONS: We report for the
      first time sustained responses to both anti-TNF-alpha and IL6R antagonists in
      refractory Takayasu arteritis. As 5/9 patients were cyclophosphamide non
      responders, we propose that biologics should now be considered ahead of
      cyclophosphamide in these young patients.

PMID- 24093735
TI  - Motivations to nurse: an exploration of what motivates students in Pacific Island
      countries to enter nursing.
AB  - The aim of this study was to explore the motivations of student nurses enrolled
      in nursing courses across a variety of Pacific Island countries. The image of
      nursing, the desire to help others, family and friends in the profession,
      personal experience, security, travel opportunities and flexibility have all been
      identified as motivators for people to enter nursing. To date, what motivates
      students in Pacific Island countries to enrol in a nursing course has not been
      investigated. An exploratory qualitative approach using focus group interviews
      with 152 nursing students was undertaken. Data were analysed using thematic
      content analysis, revealing four themes: (i) helping others; (ii) 'making a
      difference for my people'; (iii) following in the footsteps of others; and (iv)
      financial and professional gain. In a time of health and nursing workforce
      shortages, developing a deeper understanding of what drives people can be used to
      improve recruitment strategies in the future. 

PMID- 24093736
TI  - Working experiences of Iranian retired nurses: a content analysis study.
AB  - Understanding the experiences of retired nurses can be useful in increasing self
      confidence, motivation to work and work enthusiasm among nurses. The purpose of
      this study was to explore the work experiences of Iranian retired nurses. A
      qualitative design was conducted using a content analysis approach. Purposive
      sampling was used to choose the study participants. Semi-structured interviews
      were held to collect the perspectives of 20 retired nurses (10 female and 10
      male). Two main themes emerged in the data analysis: 'work problems and
      unpleasant experiences in a sense' with subthemes 'exhausting work',
      'insufficient salary', 'inappropriate relation' and 'unsuitable social position';
      and 'job satisfaction and pleasant experiences in a sense' with subthemes 'divine
      satisfaction and religious belief', 'satisfaction of patients and their
      companions' and 'love of nursing profession and relaxation experience'. The
      findings indicate the challenges that nurses face after retirement. These
      experiences will help nurse managers to adopt appropriate measures to support
      nurses after retirement. 

PMID- 24093737
TI  - Effect of systematic relaxation techniques on anxiety and pain in older patients
      undergoing abdominal surgery.
AB  - Inadequate pain control in older patients who have undergone abdominal surgery
      can lead to many complications. This study investigates the effect of systematic
      relaxation techniques on pain and anxiety in older patients undergoing abdominal
      surgery. One hundred twenty-four patients were randomly assigned into the
      experimental and control groups. The systematic relaxation techniques consisted
      of older patients in the experimental group slowly reading relaxing sentences
      during recovery in ambulation after the surgery. Patients' satisfaction with pain
      and anxiety relief was recorded, as was their use of opioid analgesia.
      Statistically significant differences in pain and anxiety, and in analgesic use,
      were reported between the patients in experimental and control groups after the
      intervention. These relaxation techniques can be incorporated into the care plan
      to reduce pain and anxiety after surgery as well as offering a measure for
      increasing the patients' independence in pain management control. 

PMID- 24093738
TI  - Comparison of three different thermometers in evaluating the body temperature of
      healthy young adult individuals.
AB  - The aim of this study was to compare the measurement values obtained with a non
      contact infrared thermometer, a tympanic thermometer and a chemical dot
      thermometer. The research population was composed of students studying in two
      departments of a university in Ankara. A total of 452 students who fit the
      inclusion criteria of the study and volunteered to participate were included in
      the sample. Body temperature measurements with different thermometers were
      performed by the same researcher at the same room temperature. Data were analyzed
      in a computerized environment by SPSS 15.0 statistical program pack and Bland
      Altman graph. Mean age of healthy young adults participating in the study was
      19.66 +/- 0.94, and 55.1% of them were female. The agreement limits for non
      contact infrared and chemical dot was between -1.30 and 0.32 degrees C; for non
      contact infrared and tympanic was between -1.26 and 0.13 degrees C; and for
      chemical dot and tympanic -0.89 and 0.74 degrees C. It was determined that,
      although the measurement values of the tympanic membrane and chemical dot
      thermometers conformed with each other, the conformity of the non-contact
      infrared thermometer was weak. 

PMID- 24093739
TI  - Examining adverse events after intensive care unit discharge: outcomes from a
      pilot questionnaire.
AB  - Adverse events are common in acute clinical settings but little is known about
      these events occurring after Intensive Care discharge. This study aimed to
      develop a reliable and valid tool for exploring clinicians' opinions of factors
      associated with post-Intensive Care adverse events. A convenience sample of
      Australian Intensive Care Liaison Nurses was invited to complete and appraise a
      questionnaire using structured guidelines. Content validity and internal
      consistency were assessed. Twelve Intensive Care Liaison Nurses completed the
      questionnaire. Cronbach?s alpha coefficient showed high internal consistency for
      the questionnaire; all 24 items on the questionnaire had coefficients greater
      than 0.852. The content validity index of the questionnaire overall was 0.76. The
      post-Intensive Care adverse events questionnaire demonstrated reliability and
      validity. It is a tool that can be used to explore clinicians? opinions of
      factors associated with these events. The tool is important as it facilitates
      further insight into the causes of post-Intensive Care adverse events. 

PMID- 24093740
TI  - Longitudinal study on infants' temperament and physical development in Beijing,
      China.
AB  - The objective of this longitudinal study is to explore the relationship between
      temperament and physical development among infants in Beijing, China. A total of
      1117 term, normal and singleton infants were followed regularly for 12 months.
      Body weight and horizontal length were measured at 42 days and monthly from the
      third to twelfth month of their lives. Infants' temperament was assessed using
      the revised Chinese infants' temperament scale when the infants were 6 months.
      There was a significant difference on temperament dimensions between infants'
      genders (P < 0.05). Infants' weight and length were significantly related to
      their parents' weight and height. Infants with positive temperaments (easy and
      intermediate) were heavier than those with negative temperaments (difficult and
      slow to warm up) (P < 0.05). The horizontal length of boys was related to their
      temperament categories (P < 0.05). Infants' weight and length were significantly
      related to their temperament category and parents' weight and height. 

PMID- 24093741
TI  - Nurses' attitudes, abilities and educational preference related to using family
      pedigrees in clinical practice.
AB  - There is growing worldwide interest in using family pedigrees to assess health
      risks for diseases and implementing potential preventive interventions for health
      promotion. Nurses have been identified as key professionals in the process of
      collecting family history information and constructing pedigrees, and there is a
      gap in the literature related to these activities. The purpose of this study was
      to determine nurses' knowledge about, attitudes towards, perceived ability to
      use, and educational preference related to inclusion of family pedigrees in
      clinical practice. The study utilized a survey method with 174 nurses and
      correlational descriptive design. Results showed 74% of the nurses were
      interested in learning about family pedigrees and 64% responded positively to
      including them in clinical practice with the belief by 88% that they are helpful
      for preventive health care. Findings may be used to advance education and
      utilization of family pedigrees for nurses in clinical practice. 

PMID- 24093742
TI  - Pregnant Turkish women with low income: their anxiety, health-promoting
      lifestyles, and related factors.
AB  - This paper presents anxiety levels, health-promoting lifestyles and related
      factors among pregnant Turkish women with low income. A descriptive correlation
      and cross-sectional study was conducted at a state maternity hospital in Western
      Turkey. The paper reports on the data (n = 195) from the Spielberg State and
      Trait Anxiety Inventory (STAI), the Health-Promoting Lifestyle Profile (HPLP) and
      a sociodemographic questionnaire. The average HPLP score was low (mean 2.57, SD
      0.42). The average STAI score was high (40.67 +/- 9.48; 46.40 +/- 8.09,
      respectively). A significant relation was detected between the trait anxiety,
      state anxiety, antenatal visit, perception of social support, living environment,
      family type and HPLP (P < 0.05). A moderately negative relation was detected
      between the mean STAI and HPLP scores. The findings indicate information and data
      should be provided for service planning and community care to support pregnant
      Turkish women with low income in communities. 

PMID- 24093743
TI  - Traditional practices used by the infertile women to become pregnant and their
      effects on the quality of life.
AB  - The present research was planned to determine the traditional practices used by
      infertile women to become pregnant and their effects on the quality of life. A
      hospital-based, descriptive and cross-sectional study. Participant Information
      Forms and SF-36 quality of life scales were applied to 269 women diagnosed as
      infertile. Some of the infertile women (32.7%) were determined to use a
      traditional method. The traditional methods used by women included herbal
      remedies (those edible and drinkable) (87.5%), sitting on the herbal mixtures
      (8%) and using both practices (4.5%). The SF-36 Mental Health component was
      determined to be better in infertile women not using traditional practices than
      those using traditional practices (P < 0.05). Considering the results of the
      study, health professionals can question women about the traditional practices
      and guide them about their damages. 

PMID- 24093744
TI  - The implementation of intentional rounding using participatory action research.
AB  - 'Intentional'/'hourly rounding' is defined as regular checks of individual
      patients carried out by health professionals at set intervals rather than a
      response to a summons via a call bell. Intentional rounding places patients at
      the heart of the ward routine including the acknowledgement of patient
      preferences and in anticipation of their needs. The aim of this study was to
      implement intentional rounding using participatory action research to increase
      patient care, increase staff productivity and the satisfaction of care provision
      from both patients and staff. Outcomes of the study revealed a drop in call bell
      use, no observable threats to patient safety, nursing staff and patient
      satisfaction with care provision. However, any future studies should consider
      staff skill mix issues including the needs of newly graduated nursing staff as
      well as the cognitive status of patients when implementing intentional rounding
      on acute care wards. 

PMID- 24093745
TI  - Investigation of risk factors of psychological acceptance and burnout syndrome
      among nurses in China.
AB  - The objectives of this study were to determine reliability of Chinese version of
      Acceptance and Action Questionnaire-II (AAQ-II), the relationship between
      psychological acceptance (PA), and burnout syndrome and their risk factors among
      nurses in China. The reliability of AAQ-II in Chinese was evaluated first by
      testing on 111 doctors and 108 nurses in China. On the number of 845 nurses
      selected from nine city hospitals by using stratified cluster sampling method,
      the Maslach Burnout Inventory-General Survey was administered to establish the
      presence of burnout, and the AAQ-II was used to measure their PA. Results showed
      that the AAQ-II in Chinese had a good test-retest reliability. PA was
      statistically significantly negatively correlated to the three dimensionalities
      of burnout among nurses in China. Male and female nurses had a significant
      difference in PA. Risk factors for burnout were age (25-44 years), marital status
      (married), gender (male), hospital department (emergency) and position (primary
      title) as well as PA. The findings provide insights into the risk factors of
      burnout in Chinese nurses and may have clinical implications in preventing
      burnout in Chinese nurses. 

PMID- 24093746
TI  - Addressing the mental health nurse shortage: undergraduate nursing students
      working as assistants in nursing in inpatient mental health settings.
AB  - The population of mental health nurses is ageing and in the next few years we can
      expect many to retire. This paper makes an argument for the employment of
      undergraduate nursing students as Assistants in Nursing (AINs) in mental health
      settings as a strategy to encourage them to consider a career in mental health
      nursing. Skill mix in nursing has been debated since at least the 1980s. It
      appears that the use of AINs in general nursing is established and will continue.
      The research suggests that with the right skill mix, nursing outcomes and safety
      are not compromised. It seems inevitable that assistants in nursing will
      increasingly be part of the mental health nursing workforce; it is timely for
      mental health nurses to lead these changes so nursing care and the future mental
      health nursing workforce stay in control of nursing. 

PMID- 24093747
TI  - Is dietary zinc protective for type 2 diabetes? Results from the Australian
      longitudinal study on women's health.
AB  - BACKGROUND: Animal studies have shown that zinc intake has protective effects
      against type 2 diabetes, but few studies have been conducted to examine this
      relationship in humans. The aim of this study is to investigate if dietary zinc
      is associated with risk of type 2 diabetes in a longitudinal study of mid-age
      Australian women. METHODS: Data were collected from a cohort of women aged 45-50
      years at baseline, participating in the Australian Longitudinal Study on Women's
      Health. A validated food frequency questionnaire was used to assess dietary
      intake and other nutrients. Predictors of 6-year incidence of type 2 diabetes
      were examined using multivariable logistic regression. RESULTS: From 8921
      participants, 333 incident cases of type 2 diabetes were identified over 6 years
      of follow-up. After adjustment for dietary and non-dietary factors, the highest
      quintile dietary zinc intake had almost half the odds of developing type 2
      diabetes (OR = 0.50, 95% C.I. 0.32-0.77) compared with the lowest quintile.
      Similar findings were observed for the zinc/iron ratio; the highest quintile had
      half the odds of developing type 2 diabetes (OR = 0.50, 95% C.I 0.30-0.83) after
      multivariable adjustment of covariates. CONCLUSIONS: Higher total dietary zinc
      intake and high zinc/iron ratio are associated with lower risk of type 2 diabetes
      in women. This finding is a positive step towards further research to determine
      if zinc supplementation may reduce the risk of developing type 2 diabetes.

PMID- 24093748
TI  - Milk thistle: a future potential anti-osteoporotic and fracture healing agent.
AB  - Osteoporosis is a progressive disease of the skeleton characterised by bone
      fragility due to a reduction in bone mass and possibly to alteration in bone
      architecture that lead to a propensity to fracture with minimum trauma. Most
      osteoporotic fractures occur at locations rich in trabecular or cancellous bone
      and usually related to post menopausal women. Recently, silymarin received
      attention due to its alternative beneficial effect on bone formation. It is a
      mixture of flavonoids with powerful antioxidant properties. This review focuses
      on the use of milk thistle or silymarin for the treatment of osteoporosis that
      may be related to fracture bone. Silymarin shows potent antioxidant herb that may
      modulate multiple genes in favour of helping to build bone and prevent bone loss.
      In the mouse fracture healing model, silymarin supplementation improved tibial
      healing with elevated BMD and serum levels of ALP and osteocalcin. Silymarin also
      demonstrated clear estrogenic antiosteoporotic effects in bone structure.
      Silymarin appears to play a crucial role to prevent bone loss and might regulate
      osteogenesis and may be beneficial for fracture healing. If silymarin is
      considered for the use of post menopausal women, it may be used for the treatment
      of osteoporosis. It would be of great benefit to postmenopausal women to develop
      an oestrogen antagonist that is as potent and efficacious as oestrogen in
      preventing bone loss without the major side effect associated with HRT. 

PMID- 24093749
TI  - Drug therapy of neuropathic pain: current developments and future perspectives.
AB  - Understanding mechanism of neuropathic pain is too complex and involves both
      peripheral and central pathophysiological phenomenon. Accordingly the treatment
      of neuropathic pain is also very complex and is unsatisfactory. The present
      review attempts to discuss the currently employed pharmacological agents for the
      management of neuropathic pain including anti-depressants, anti-convulsants, NMDA
      receptor antagonists, topical & local anesthetics, and upload analgesics.
      However, the existing pharmacotherapy has marginal efficacy and significant side
      effects. The review also gives an insight into various pharmacological agents
      with potential neuropathic pain attenuating properties in experimental models
      that include NSAIDs, corticosteroids, ion channel blockers (Ca(2+), Na(+), K(+),
      and TRP channel); ion exchange modulators (NCE and NHE); ion/molecule transport
      modulators (NKCC-1 and glycine); receptor modulators (kinin, histamine, 5-HT1A,
      dopamine, alpha & beta adrenergic, purinergic, excitatory amino acid, sigma,
      ORL1, endothelin, melanocortin, ephrin and PAR); enzyme inhibitors (cytosolic
      kinase, metalloproteinase, protease, vasopeptidase, D-amino acid oxidase, fatty
      acid amide hydrolase, aldose reductase and sorbitol dehydrogenase); other ligands
      (AGE, RAGEs, neuropeptides, neurotrophic factor, complement cascade, cytokine,
      glial cell & gap junction, nitrous oxide, growth factor, cell adhesion molecule
      and neuronal sprouting molecule). Moreover, some advanced therapeutic approaches
      such as neuronal cell transplantation, stem cell therapy, anti-sense
      oligonucleotide and recombinant therapy have also been dicussed. 

PMID- 24093750
TI  - A way to curb phosphorus toxicity in the environment: use of polyphosphate
      reservoir of cyanobacteria and microalga as a safe alternative phosphorus
      biofertilizer for Indian agriculture.

PMID- 24093751
TI  - Germline variants in MRE11/RAD50/NBN complex genes in childhood leukemia.
AB  - BACKGROUND: The MRE11, RAD50, and NBN genes encode proteins of the MRE11-RAD50
      NBN (MRN) complex involved in cellular response to DNA damage and the maintenance
      of genome stability. In our previous study we showed that the germline p.I171V
      mutation in NBN may be considered as a risk factor in the development of
      childhood acute lymphoblastic leukemia (ALL) and some specific haplotypes of that
      gene may be associated with childhood leukemia. These findings raise important
      questions about the role of mutations in others genes of the MRN complex in
      childhood leukemia. The aim of this study was to answer the question whether
      MRE11 and RAD50 alterations may be associated with childhood ALL or AML. METHODS:
      We estimated the frequency of constitutional mutations and polymorphisms in
      selected regions of MRE11, RAD50, and NBN in the group of 220 children diagnosed
      with childhood leukemias and controls (n=504/2200). The analysis was performed by
      specific amplification of region of interest by PCR and followed by multi
      temperature single-strand conformation polymorphism (PCR-MSSCP) technique. We
      performed two molecular tests to examine any potential function of the detected
      the c.551+19G>A SNP in RAD50 gene. To our knowledge, this is the first analysis
      of the MRE11, RAD50 and NBN genes in childhood leukemia. RESULTS: The frequency
      of either the AA genotype or A allele of RAD50_rs17166050 were significantly
      different in controls compared to leukemia group (ALL+AML) (p<0.0019 and
      p<0.0019, respectively). The cDNA analysis of AA or GA genotypes carriers has not
      revealed evidence of splicing abnormality of RAD50 pre-mRNA. We measured the
      allelic-specific expression of G and A alleles at c.551+19G>A and the
      statistically significant overexpression of the G allele has been observed.
      Additionally we confirmed the higher incidence of the p.I171V mutation in the
      leukemia group (7/220) than among controls (12/2400) (p<0.0001). CONCLUSION: The
      formerly reported sequence variants in the RAD50 and MRE11 gene may not
      constitute a risk factor of childhood ALL in Polish population. The
      RAD50_rs17166050 variant allele is linked to decreased ALL risk (p<0.0009,
      OR=0.6358 (95%CI: 0.4854-0.8327)). Despite the fact that there is no splicing
      abnormality in carriers of the variant allele but an excess of the G over the A
      allele was consistently observed. This data demonstrate that some specific
      alternations of the RAD50 gene may be associated with childhood ALL.

PMID- 24093753
TI  - Carbyne from first principles: chain of C atoms, a nanorod or a nanorope.
AB  - We report an extensive study of the properties of carbyne using first-principles
      calculations. We investigate carbyne's mechanical response to tension, bending,
      and torsion deformations. Under tension, carbyne is about twice as stiff as the
      stiffest known materials and has an unrivaled specific strength of up to 7.5 *
      10(7) N.m/kg, requiring a force of ~10 nN to break a single atomic chain. Carbyne
      has a fairly large room-temperature persistence length of about 14 nm.
      Surprisingly, the torsional stiffness of carbyne can be zero but can be "switched
      on" by appropriate functional groups at the ends. Further, under appropriate
      termination, carbyne can be switched into a magnetic semiconductor state by
      mechanical twisting. We reconstruct the equivalent continuum elasticity
      representation, providing the full set of elastic moduli for carbyne, showing its
      extreme mechanical performance (e.g., a nominal Young's modulus of 32.7 TPa with
      an effective mechanical thickness of 0.772 A). We also find an interesting
      coupling between strain and band gap of carbyne, which is strongly increased
      under tension, from 2.6 to 4.7 eV under a 10% strain. Finally, we study the
      performance of carbyne as a nanoscale electrical cable and estimate its chemical
      stability against self-aggregation, finding an activation barrier of 0.6 eV for
      the carbyne-carbyne cross-linking reaction and an equilibrium cross-link density
      for two parallel carbyne chains of 1 cross-link per 17 C atoms (2.2 nm). 

PMID- 24093752
TI  - A recombinant pseudotyped lentivirus expressing the envelope glycoprotein of
      hantaan virus induced protective immunity in mice.
AB  - BACKGROUND: Hantaviruses cause acute hemorrhagic fever with renal syndrome
      (HFRS). Currently, several types of inactivated HFRS vaccines are widely used,
      however the limited ability of these immunogen to elicit neutralizing antibodies
      restricts vaccine efficacy. Development of an effective vaccine to overcome this
      weakness is must. METHODS: In the present study, a recombinant pseudotyped
      lentivirus bearing the hantaan virus (HTNV) envelope glycoproteins (GP), rLV-M,
      was constructed. C57BL/6 mice were immunized with the rLV-M and a series of
      immunological assays were conducted to determine the immunogenicity of the
      recombinant pseudotyped lentivirus. The humoral and cell-mediated immune
      responses induced by rLV-M were compared with those of the inactivated HFRS
      vaccine. RESULTS: Indirect immunofluorescence assay (IFA) showed the rLV-M
      expressed target proteins in HEK-293 cells. In mice, the rLV-M efficiently
      induced GP-specific humoral responses and protection against HTNV infection.
      Furthermore, the rLV-M induced higher neutralizing antibody titers than the
      inactivated HFRS vaccine control. CONCLUSIONS: The results indicated the
      potential of using a pseudotyped lentivirus as a delivery vector for a hantavirus
      vaccine immunogen.

PMID- 24093754
TI  - Oxidation reactions of 1- and 2-naphthols: an experimental and theoretical study.
AB  - The transients formed during the reactions of oxidizing radicals with 1-naphthol
      (1) and 2-naphthol (2) in aqueous medium have been investigated by pulse
      radiolysis with detection by absorption spectroscopy and density functional
      theory (DFT) calculations. The transient spectra formed on hydroxyl radical
      ((*)OH) reactions of 1 and 2 exhibited lambda(max) at 340 and 350 nm at neutral
      pH. The rate constants of the (*)OH reactions of 1 (2) were determined from build
      up kinetics at lambda(max) of the transients as (9.63 +/- 0.04) * 10(9) M(-1) s(
      1) ((7.31 +/- 0.11) * 10(9) M(-1) s(-1)). DFT calculations using the B3LYP/6
      31+G(d,p) method have been performed to locate favorable reaction sites in both 1
      and 2 and identification of the pertinent transients responsible for experimental
      results. Calculations demonstrated that (*)OH additions can occur mostly at C1
      and C4 positions of 1, and at C1 and C8 positions of 2. Among several isomeric
      (*)OH adducts possible, the C1 adduct was found to be energetically most stable
      both in 1 and 2. Time-dependent density functional theory (TDDFT) calculations in
      the solution phase has shown that the experimental spectrum of 1 was mainly
      attributed by 1a4 (kinetically driven (*)OH-adduct) formed via the addition of
      (*)OH at the C4 position which was 0.73 kcal/mol endergonic compared to 1a1
      (thermodynamic (*)OH adduct), whereas 2a1 (thermodynamic/kinetic (*)OH-adduct)
      was mainly responsible for the experimental spectrum of 2. Naphthoxyl radicals of
      1 and 2 have been predicted as the transient formed in the reaction of (*)OH at
      basic pH. In addition, the same transient species resulted from the reactions of
      oxide radical ion (O(*-)) at pH ~ 13 and azide radical (N3(*)) at pH 7 with 1 and
      2. Further, UV photolysis of aqueous solutions of 1 and 2 containing H2O2
      (UV/H2O2) were used for the (*)OH induced oxidation product formations up on 60%
      degradations of 1 and 2; profiling of the oxidation products were performed by
      using an ultraperformance liquid chromatography quadrupole time-of-flight mass
      spectrometry (UPLC-Q-TOF-MS) method. According to the UPLC-Q-TOF-MS analyses, the
      preliminary oxidation products are limited to dihydroxy naphthalenes and
      naphthoquinones with N2-saturation, while some additional products (mainly
      isomeric monohydroxy-naphthoquinones) have been observed in the degradations of 1
      and 2 in the presence of O2. We postulate that dihydroxy naphthalenes are derived
      explicitly from the most favorable (*)OH-adducts speculated (preference is in
      terms of the kinetic/thermodynamic dominancy of transients) by using theoretical
      calculations which in turn substantiate the proposed reaction mechanisms. The
      observations of (*)OH-adducts for an aromatic phenol (herein for both 1 and 2 at
      pH 7) rather than phenoxyl type radical in the pulse radiolysis experiments is a
      distinct and unique illustration. The present study provides a meaningful basis
      for the early stages associated with the (*)OH initiated advanced oxidation
      processes of 1- and 2-naphthols.

PMID- 24093755
TI  - HPTLC analysis, antioxidant, anti-inflammatory and antiproliferative activities
      of Arisaema tortuosum tuber extract.
AB  - CONTEXT: Oxidative stress and inflammation are related to several chronic
      diseases including cancer and atherosclerosis. Arisaema tortuosum (Wall.) Schott
      (Araceae) is an Indian folk medicinal herb traditionally used for treatment of
      various diseases related to inflammation and stress. OBJECTIVE: This study was
      carried out for HPTLC analysis and evaluation of antioxidant, anti-inflammatory
      and antiproliferative activities of a methanol extract of A. tortuosum tuber.
      MATERIALS AND METHODS: The antioxidant activities of methanol extract of A.
      tortuosum tuber (1 mg/mL) were evaluated by DPPH, ABTS and FRAP assays and anti
      inflammatory effects by diene-conjugate and beta-glucuronidase assays, with in
      vitro tumor growth inhibition on HeLa cancer cells. The results for antioxidant
      and anti-inflammatory effects were compared using Trolox and salicylic acid as
      reference compounds, respectively. RESULTS: The TLC and HPTLC analysis showed the
      presence of quercetin, rutin, luteolin and lectin (Rf values 0.97, 0.53, 0.59 and
      1.58, respectively). The methanol fraction of tuber exhibit higher activity in
      each antioxidant system with a special attention for DPPH (IC50 = 852 MUg/mL),
      ABTS (IC50 = 532 MUg/mL), and FRAP (IC50 = 458 MUg/mL), as compared with Trolox
      as standard, with a remarkable amount of phenolics (86.2 mg/100 g) and flavonoids
      (175.5 mg/100 g), along with potent anti-inflammatory activity indicated by diene
      conjugate (86.20%) and beta-glucuronidase (92.92%) inhibition, as compared with
      salicylic acid as reference compound. The antiproliferative activity at 100 mg/mL
      was 88% inhibition with HeLa cells. The inhibition of HeLa cell proliferation was
      greatest (p < 0.001) with the 100 mg/mL A. tortuosum tuber extract treatments and
      least with the 25 mg/mL dose. DISCUSSION AND CONCLUSION: Our results suggested
      that A. tortuosum tuber might be used as a promising and potent antioxidant, anti
      inflammatory, and antiproliferative agent and might be used for standardization
      of potential drug after successful isolation and characterization of bioactive
      compounds.

PMID- 24093756
TI  - Quality of life and adherence to antiretroviral therapy in Southern Brazil.
AB  - The absence of or limited adherence to treatment is the main cause for the
      failure of Highly Active Antiretroviral Therapy (HAART). In Brazil, adherence to
      antiretroviral therapy has been lower than the recommended levels. Although HAART
      may produce adverse reactions, failure to comply with it may aggravate patients'
      health status and impair Quality of Life (QoL). The QoL of individuals living
      chronically with HIV and AIDS has been considered one of the main treatment
      outcomes. This study is part of a 225-day prospective trial in which participants
      were enrolled in two different modalities of follow-up: the usual model medical
      follow-up or an intervention based on the Medication Adherence Training
      Instrument (MATI). The WHOQOL-HIV BREF questionnaire was used to evaluate QoL of
      research participants in both groups on the 15th and 225th days of follow-up
      after the baseline assessment. The result of this study revealed no significant
      differences of WHOQOL-HIV BREF scores between participants allocated to MATI and
      non-MATI groups in the first assessment. However, there was a significant
      difference between the scores obtained on the 15th and 225th days in the domain
      related to spirituality and personal beliefs irrespective of the modality of
      follow-up. Other domains of the WHOQOL-HOV BREF remained unchanged. These results
      indicate that, in this sample, personal beliefs and spirituality may be relevant
      subjects to explain sustained levels of adherence to HAART. 

PMID- 24093757
TI  - Comparative analysis of differential network modularity in tissue specific normal
      and cancer protein interaction networks.
AB  - BACKGROUND: Large scale understanding of complex and dynamic alterations in
      cellular and subcellular levels during cancer in contrast to normal condition has
      facilitated the emergence of sophisticated systemic approaches like network
      biology in recent times. As most biological networks show modular properties, the
      analysis of differential modularity between normal and cancer protein interaction
      networks can be a good way to understand cancer more significantly. Two aspects
      of biological network modularity e.g. detection of molecular complexes (potential
      modules or clusters) and identification of crucial nodes forming the overlapping
      modules have been considered in this regard. METHODS: In the current study, the
      computational analysis of previously published protein interaction networks
      (PINs) has been conducted to identify the molecular complexes and crucial nodes
      of the networks. Protein molecules involved in ten major cancer signal
      transduction pathways were used to construct the networks based on expression
      data of five tissues e.g. bone, breast, colon, kidney and liver in both normal
      and cancer conditions. MCODE (molecular complex detection) and ModuLand methods
      have been used to identify the molecular complexes and crucial nodes of the
      networks respectively. RESULTS: In case of all tissues, cancer PINs show higher
      level of clustering (formation of molecular complexes) than the normal ones. In
      contrast, lower level modular overlapping is found in cancer PINs than the normal
      ones. Thus a proposition can be made regarding the formation of some giant nodes
      in the cancer networks with very high degree and resulting in reduced overlapping
      among the network modules though the predicted molecular complex numbers are
      higher in cancer conditions. CONCLUSION: The study predicts some major molecular
      complexes that might act as the important regulators in cancer progression. The
      crucial nodes identified in this study can be potential drug targets to combat
      cancer.

PMID- 24093758
TI  - Transcriptome analyses of a Chinese hazelnut species Corylus mandshurica.
AB  - BACKGROUND: Corylus was renowned for its production of hazelnut and taxol. To
      understand the local adaptation of Chinese species and speed up breeding efforts
      in China, we analyzed the leaf transcriptome of Corylus mandshurica, which had a
      high tolerance to fungal infections and cold. RESULTS: A total of 12,255,030
      clean pair-end reads were generated and then assembled into 37,846 Expressed
      Sequence Tag (EST) sequences. During functional annotation, 26,565 ESTs were
      annotated with Gene Ontology (GO) terms using Blast2go and 11,056 ESTs were
      grouped into the Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways using
      KEGG Automatic Annotation Server (KAAS). We identified 45 ESTs that were
      homologous to enzymes and transcription factors responsible for taxol synthesis.
      The most differentiated orthologs between C. mandshurica and a European congener,
      C. avellana, were enriched in stress tolerance to fungal resistance and cold.
      CONCLUSIONS: In this study, we detected a set of genes related to taxol synthesis
      in a taxol-producing angiosperm species for the first time and found a close
      relationship between most differentiated genes and different adaptations to
      fungal infection and cold in C. mandshurica and C. avellana. These findings
      provided tools to improve our understanding of local adaptation, genetic breeding
      and taxol production in hazelnut.

PMID- 24093759
TI  - Animal models of obsessive-compulsive spectrum disorders.
AB  - Obsessive-compulsive disorder (OCD) and related conditions (trichotillomania,
      pathological skin-picking, pathological nail-biting) are common and disabling.
      Current treatment approaches fail to help a significant proportion of patients.
      Multiple tiers of evidence link these conditions with underlying dysregulation of
      particular cortico-subcortical circuitry and monoamine systems, which represent
      targets for treatment. Animal models designed to capture aspects of these
      conditions are critical for several reasons. First, they help in furthering our
      understanding of neuroanatomical and neurochemical underpinnings of the obsessive
      compulsive (OC) spectrum. Second, they help to account for the brain mechanisms
      by which existing treatments (pharmacotherapy, psychotherapy, deep brain
      stimulation) exert their beneficial effects on patients. Third, they inform the
      search for novel treatments. This article provides a critique of key animal
      models for selected OC spectrum disorders, beginning with initial work relating
      to anxiety, but moving on to recent developments in domains of genetic,
      pharmacological, cognitive, and ethological models. We find that there is a
      burgeoning literature in these areas with important ramifications, which are
      considered, along with salient future lines of research. 

PMID- 24093760
TI  - Association between body mass index, sexually transmitted infections, and
      contraceptive compliance.
AB  - BACKGROUND: Recent studies have examined the relationship between body mass index
      (BMI) and sexual behaviors, but little information exists on this relationship
      among racially diverse, low-income women using objectively measured clinical
      data. The purpose of this study was to examine the association between BMI and
      sexual behaviors, rates of sexually transmitted infections (STIs) and unintended
      pregnancy, and contraceptive adherence among adolescent and young adult women.
      METHODS: As part of a larger study, 1,015 Hispanic (54.2%), Black (18.6%) and
      White (24.8%) women aged 16 to 24 years seeking family planning services at
      publicly funded reproductive health clinics provided data on their baseline
      sexual behaviors, and contraceptive use and pregnancy history over 12 months.
      Objective clinical data were available from medical records at baseline (i.e.,
      height, weight, and Papanicolaou [Pap] smear results), and over a 12-month period
      (i.e., STI results). Multivariable analyses were used to compare sexual
      behaviors, STI rates, contraceptive compliance, and unintended pregnancy rates
      between obese, overweight, and normal weight participants after adjusting for
      age, race/ethnicity, and other confounders. RESULTS: Overall, 423 (36.6%), 304
      (26.3%), and 288 (24.9%) participants were classified as normal weight,
      overweight, and obese, respectively. No statistically significant association was
      observed between BMI and sexual behaviors, STI rates (overweight odds ratio [OR]
      0.67; 95% confidence interval [95% CI] [0.4, 1.08]; obese OR 0.68; 95% CI [0.42,
      1.10]); contraceptive compliance (overweight OR 0.89; 95% CI [0.69, 1.16]; obese
      OR 0.89; 95% CI 0.68, 1.16]), or unintended pregnancy (overweight OR 1.08 95% CI
      [0.73, 1.60]; obese OR 1.09; 95% CI [0.72, 1.63]). CONCLUSION: STI history and
      contraceptive compliance did not vary by BMI. Therefore, all women should receive
      equal contraceptive counseling (including condoms) to reduce the risk of
      unplanned pregnancy and STIs.

PMID- 24093761
TI  - Facile synthesis of peptidyl salicylaldehyde esters and its use in cyclic peptide
      synthesis.
AB  - An efficient solid phase synthetic protocol for salicylaldehyde ester peptides is
      reported. With a Ser or Thr at the N-terminus, these salicylaldehyde ester
      peptides can be easily converted to Ser/Thr containing cyclic peptides. 

PMID- 24093762
TI  - In situ synthesis and immobilization of metallic nanoparticles on a calixarene
      monolayer.
AB  - A covalently immobilized calix[7]hydroquinone monolayer was used as the host
      matrix to synthesize metallic NPs using an in situ redox process. The
      characteristics of different metallic ions that affect the synthesis process were
      studied. Metallic ions with less charges, lower oxidation state in the reaction,
      and higher standard redox potential provided better yield. Bimetallic NPs with a
      core-shell structure were synthesized by a sequential deposition of different
      metals on the same monolayer. The process was applied to form a layer of
      immobilized NPs on flat and curved surfaces. The ability to synthesize and
      immobilize well-controlled NPs on different surfaces has promising applications
      in decoration of irregular surfaces of miniaturized, three-dimensional objects. 

PMID- 24093763
TI  - Genetic variant of single-nucleotide polymorphism is associated with risk of
      esophageal squamous cell carcinoma.
AB  - AIM: The genetic polymorphisms of the alcohol metabolizing enzymes alcohol
      dehydrogenase 1B (ADH1B) rs1229984 may modulate individual differences in alcohol
      oxidizing capability. A case-control study was conducted to evaluate the genetic
      effects of these functional single-nucleotide polymorphisms on the development of
      esophageal cancer. METHODS: Here, a total of 1001 esophageal squamous cell
      carcinoma (ESCC) cases and 1391 controls were recruited. Genotypes were
      determined by DNA sequencing. Differences in the distributions of demographic
      characteristics, selected variables, and genotypes of ADH1B rs1229984 variants
      between cases and controls were evaluated using the chi(2) test. Associations
      between ADH1B genotypes and the risk of esophageal cancer were estimated by
      computing the odds ratios (ORs) and their 95% confidence intervals (CIs) using
      logistic regression analyses for crude ORs and adjusted ORs when adjusting for
      age, gender, and tobacco use status. RESULTS: There were no significant
      differences between ESCC patients and controls in terms of age and sex
      distributions, suggesting that the frequency matching was adequate. However,
      significantly, more smokers were presented among the ESCC cases than among
      controls (63.1% vs. 49.2%; p=2.14 * 10-11). Smokers had an increased risk for
      developing ESCC (adjusted OR=2.17, 95% CI=1.78-2.64). This result clearly
      indicated that smoking is a risk factor for the ESCC in our study population. We
      found that subjects carrying the rs1229984 GG genotype had significantly
      increased risk of ESCC (adjusted OR, 2.81; 95% CI, 2.18-3.62; p=1.05 * 10-15)
      compared with the AA genotype. CONCLUSION: The functional polymorphisms ADH1B
      rs1229984 may contribute to susceptibility to esophageal cancer.

PMID- 24093764
TI  - Preparation and characterization of glycyrrhetinic acid-modified stearic acid
      grafted chitosan micelles.
AB  - Stearic acid-grafted chitosan (CS-SA) and glycyrrhetinic acid-conjugated stearic
      acid-grafted chitosan (GA-CS-SA) were synthesized and were further used for the
      preparation of micelles. The substitution degree (SD) of SA and GA on CS was
      measured. The physicochemical properties of CS-SA and GA-CS-SA micelles such as
      critical micelle concentration (CMC), aggregation number of hydrophobic micro
      domain (AN), particle size, zeta potential, and morphology were also determined.
      The CMC of GA-CS-SA was about 17.49 MUg/mL, which was relatively low. Its AN was
      2.09. The GA-CS-SA micelles showed spherical shape with mean diameter of 121.1 nm
      and had positive charge, which suggested that GA-CS-SA could be a good carrier of
      cancer drug. 

PMID- 24093765
TI  - Dye-attached magnetic poly(hydroxyethyl methacrylate) nanospheres for albumin
      depletion from human plasma.
AB  - The selective binding of albumin on dye-affinity nanospheres was combined with
      magnetic properties as an alternative approach for albumin depletion from human
      plasma. Magnetic poly(hydroxyethyl methacrylate) (mPHEMA) nanospheres were
      synthesized using mini-emulsion polymerization method in the presence of
      magnetite powder. The specific surface area of the mPHEMA nanospheres was found
      to be 1302 m(2)/g. Subsequent to Cibacron Blue F3GA (CB) immobilization onto
      mPHEMA nanospheres, a serial characterization processing was implemented. The
      quantity of immobilized CB was calculated as 800 MUmol/g. Ultimately, albumin
      adsorption performance of the CB-attached mPHEMA nanospheres from both aqueous
      dissolving medium and human plasma were explored.

PMID- 24093770
TI  - Non-invasive detection of microvascular changes in a paediatric and adolescent
      population with type 1 diabetes: a pilot cross-sectional study.
AB  - BACKGROUND: The detection of microvascular damage in type 1 diabetes is difficult
      and traditional investigations do not detect changes until they are well
      established. The purpose of this study was to investigate the combined ability of
      nailfold capillaroscopy, laser Doppler flowmetry, retinal vessel analysis and 24
      hr ambulatory blood pressure monitoring to detect early microvascular changes in
      a paediatric and adolescent population with type 1 diabetes. METHODS: Patients
      aged between 8 - 18 years with type I diabetes and no other autoimmune conditions
      were studied. The participants underwent the above cardiac and vascular
      investigations in a single three-hour session. Standard parameters including
      HbA1c were also investigated. Associations between all parameters were described
      by correlation analysis. Fisher's exact and t-tests determined the association
      with clinical findings. RESULTS: 26 participants were recruited. The mean HbA1c
      was 8.1% (SD +/- 1.1) with a mean duration of type 1 diabetes of 7.9 years (SD +/
      3.4). Three participants had microalbuminuria and one had early signs of
      retinopathy. Participants with microvascular complications had more avascular
      areas on nailfold capillaroscopy (p = 0.03). Recent HbA1c was positively
      associated with the number of nailfold microhaemorrhages (p = 0.03) Decreased
      baseline perfusion by laser Doppler flowmetry was associated with increased
      capillary density (p = 0.001) and an increased number of microaneurysms (p =
      0.04) on nailfold capillaroscopy. CONCLUSIONS: This pilot study has shown that in
      children and adolescents with established type 1 diabetes, abnormal
      microvasculature can be detected by these investigations. These markers were also
      positively associated with evidence of suboptimal diabetes control as assessed by
      HbA1c. Further research will be necessary to determine the practical role of
      these investigations in the management and progress of the complications of type
      1 diabetes. TRIAL REGISTRATION: Clinical Trial number NCT01279928,
      ClinicalTrials.gov.

PMID- 24093771
TI  - The role of inflammation in the progression of ocular surface damage in children
      following allogeneic haematopoietic cell transplantation.
AB  - The aim of the study was to evaluate HLA-DR expression and cellular morphology of
      the conjunctival epithelium cells in children who underwent haematopoietic cell
      transplantation, and to assess the relation between HLA-DR expression and
      cellular morphology. Impression cytology with staining was used to visualize
      epithelium cells, whereas immunohistochemistry was applied to assess HLA-DR
      expression. Elevated HLA-DR expression and increased cytological abnormalities
      were observed in the study group when compared to the controls. An increase in
      HLA-DR expression was accompanied by a decrease in the number of eyes with normal
      epithelium morphology together with the increase in squamous metaplasia features.
      We can conclude that inflammation of conjunctiva can follow stem cell
      allotransplantation. Ocular surface inflammation may lead to squamous metaplasia
      of the conjunctiva. 

PMID- 24093767
TI  - Genotype- and phenotype-guided management of congenital long QT syndrome.
AB  - Congenital long QT syndrome (LQTS) is a genetically heterogeneous group of
      heritable disorders of myocardial repolarization linked by the shared clinical
      phenotype of QT prolongation on electrocardiogram and an increased risk of
      potentially life-threatening cardiac arrhythmias. At the molecular level,
      mutations in 15 distinct LQTS-susceptibility genes that encode ion channel pore
      forming alpha-subunits and accessory beta-subunits central to the
      electromechanical function of the heart have been implicated in its pathogenesis.
      Over the past 2 decades, our evolving understanding of the electrophysiological
      mechanisms by which specific genetic substrates perturb the cardiac action
      potential has translated into vastly improved approaches to the diagnosis, risk
      stratification, and treatment of patients with LQTS. In this review, we describe
      how our understanding of the molecular underpinnings of LQTS has yielded numerous
      clinically meaningful genotype-phenotype correlations and how these insights have
      translated into genotype- and phenotype-guided approaches to the clinical
      management of LQTS. 

PMID- 24093772
TI  - Selective depletion of alloreactive donor T cells leads to elimination of graft
      versus-host reactivity and stimulates graft-versus-leukaemia/myeloma effect.
AB  - Graft-versus-host disease is a severe complication of allogeneic stem cell
      transplantation. The major role is played by alloreactive donor T-cell clones
      leading to host tissue damage. Selective depletion is a strategy to eliminate
      host-reactive donor T cells from haematopoietic stem cell allografts to prevent
      graft-versus-host disease while conserving useful donor immune functions. We have
      used irradiated peripheral blood mononuclear cells from cancer patients and
      healthy donor cells as responder cells in primary mixed leukocyte reaction. To
      prepare graft-versus leukaemia/myeloma-specific T cells, alloreactive T cells in
      primary mixed leukocyte reaction were depleted with anti-CD25 immunotoxin. The
      remaining T cells had insignificant alloreactivity in secondary mixed leukocyte
      reaction. Then, allodepleted donor T cells were repeatedly stimulated using
      purified leukaemia/tumour cells from the same cancer patient. Leukaemia/tumour
      reactive donor T cells were purified using cell sorter on the basis of CD4 and
      CD8 activation. Their specificity was tested in nonradioactive cytotoxicity test.
      We performed 22 reactions (15 samples with leukemic and 7 samples with multiple
      myeloma cells). Selective depletion of alloreactive donor T cells with anti-CD25
      immunotoxin led to significant depletion (99.2-100 %, median 99.7%). The effect
      of donor T cells was well preserved, while the graft-versus-host reactivation of
      donor cells was negligible, even after repeated stimulation with patient's non
      tumour cells. Thus, it is possible to selectively deplete donor alloreactive T
      cells with anti-CD25 immunotoxin. In the cases of leukaemia patients, a strong
      graft-versus-leukaemia reactivity was noticed in allodepleted donor T cells; in
      myeloma patients, graft-versus-myeloma reactivity was less significant. 

PMID- 24093773
TI  - Serum levels of matrix metalloproteinases 2 and 9 and TGFBR2 gene screening in
      patients with ascending aortic dilatation.
AB  - Development of ascending aortic dilatation (AAD) in about 10 % of patients
      operated for aortic valve disease (AVD) is probably based on intrinsic pathology
      of the aortic wall. This may involve an abnormality in the process of
      extracellular matrix remodelling. The present study evaluated the serum levels of
      specific metalloproteinases (MMP-2 and MMP-9) and investigated the gene for
      transforming growth factor receptor 2 (TGFBR2) in 28 patients with AVD associated
      with AAD (mean age 60.6 years), in 29 patients (68.9 years) with AVD without AAD,
      and in 30 healthy controls (45.3 years). The serum levels of MMPs were determined
      by ELISA. Further, we focused on genetic screening of the TGFBR2 gene. Plasma MMP
      2 concentrations were significantly higher in the groups of patients compared to
      the controls: median 1315.0 (mean 1265.2 +/- SD 391.3) in AVD with AAD, 1240.0
      (1327.8 +/- 352.5) in AVD without AAD versus 902.5 (872.3 +/- 166.2) ng/ml in the
      healthy controls, in both cases P < 0.001. The serum levels of MMP-9 were
      significantly higher in AVD with AAD patients [107.0 (202.3 +/- 313.0)] and in
      AVD without AAD patients [107.0 (185.8 +/- 264.3)] compared to the healthy
      controls [14.5 (21.2 +/- 24.8) ng/ml], in both cases P < 0.001. No significant
      correlation was observed between plasma MMP-2 and MMP-9 and ascending aorta
      diameter. Genetic screening did not reveal any variation in the TGFBR2 gene in
      the patients. Measurement of MMP levels is a simple and relatively rapid
      laboratory test that could be used as a biochemical indicator when evaluated in
      combination with imaging techniques. 

PMID- 24093774
TI  - Inhibition of mTORC1 by SU6656, the selective Src kinase inhibitor, is not
      accompanied by activation of Akt/PKB signalling in melanoma cells.
AB  - The mammalian target of rapamycin (mTOR) is a Ser/Thr protein kinase conserved in
      all eukaryotes that plays a key role in cell growth and is a central effector of
      several pathways regulating essential cell functions. Hyperactivation of the
      mTORdependent signalling pathway occurs in many human diseases and may be a
      selective target for their therapy. However, the dual nature of mTOR, existing in
      two multiprotein complexes mTORC1 and mTORC2 driven by different feedback loops,
      decreases the therapeutic effects of rapamycin, the specific mTOR inhibitor. In
      the present study we demonstrate that the mTORC1 signalling pathway is highly
      activated in human melanoma cells and that up-regulation of this pathway along
      with the growth and malignity of these cells could be suppressed by disruption of
      the Src activity. SU6656, the selective inhibitor of the Src kinase activity,
      decreased up-regulation of the mTORC1 signalling and moreover, unlike rapamycin,
      it did not induce the activation of Akt/PKB and its downstream targets in HBL
      melanoma cells. The Src protein was found to be associated with raptor in the
      mTORC1 complex immunoprecipitated from these cells, suggesting that the Src
      activity might be a new attractive target for monotherapeutic inhibition of the
      up-regulated mTORC1 signalling pathway. 

PMID- 24093775
TI  - Tagging rs10811661 variant at CDKN2A/2B locus is not associated with type 2
      diabetes mellitus in Czech population.
AB  - Genome-wide association studies have resulted in the identification of the
      CDKN2A/2B locus as an important genetic determinant of type 2 diabetes mellitus
      development. The aim of this study was to investigate the role of this locus in
      the development of type 2 diabetes mellitus in Czech Slavonic population. Groups
      of 1,149 type 2 diabetic patients and a group of 2,312 healthy controls, both of
      Czech origin, were successfully genotyped for the rs10811661 CDK2A/2B tagging
      polymorphism. The "risky" TT genotype frequencies were almost identical in both
      examined groups (69.3 % in patients and 68.9 % in controls, P = 0.52; OR [95% CI]
      = 1.02 [0.87 - 1.19] for TT versus C allele carriers). Similar negative results
      were obtained when males (P = 0.93) and females (P = 0.23) were analysed
      separately. We have not confirmed the association between rs10811661 SNP and
      susceptibility to the type 2 diabetes mellitus in Czech Slavonic population. 

PMID- 24093776
TI  - Non-overlapping activities of ADF and cofilin-1 during the migration of
      metastatic breast tumor cells.
AB  - BACKGROUND: ADF/cofilin proteins are key modulators of actin dynamics in
      metastasis and invasion of cancer cells. Here we focused on the roles of ADF and
      cofilin-1 individually in the development of polarized migration of rat mammary
      adenocarcinoma (MTLn3) cells, which express nearly equal amounts of each protein.
      Small interference RNA (siRNA) technology was used to knockdown (KD) the
      expression of ADF and cofilin-1 independently. RESULTS: Either ADF KD or cofilin
      KD caused cell elongation, a reduction in cell area, a decreased ability to form
      invadopodia, and a decreased percentage of polarized cells after 180 s of
      epidermal growth factor stimulation. Moreover, ADF KD or cofilin KD increased the
      rate of cell migration and the time of lamellipodia protrusion but through
      different mechanisms: lamellipodia protrude more frequently in ADF KD cells and
      are more persistent in cofilin KD cells. ADF KD cells showed a significant
      increase in F-actin aggregates, whereas cofilin KD cells showed a significant
      increase in prominent F-actin bundles and increased cell adhesion. Focal adhesion
      area and cell adhesion in cofilin KD cells were returned to control levels by
      expressing exogenous cofilin but not ADF. Return to control rates of cell
      migration in ADF KD cells was achieved by expression of exogenous ADF but not
      cofilin, whereas in cofilin KD cells, expression of cofilin efficiently rescued
      control migration rates. CONCLUSION: Although ADF and cofilin have many redundant
      functions, each of these isoforms has functional differences that affect F-actin
      structures, cell adhesion and lamellipodial dynamics, all of which are important
      determinants of cell migration.

PMID- 24093777
TI  - Annotation and characterization of the Plasmodium vivax rhoptry neck protein 4
      (PvRON4).
AB  - BACKGROUND: The tight junction (TJ) is one of the most important structures
      established during merozoite invasion of host cells and a large amount of
      proteins stored in Toxoplasma and Plasmodium parasites' apical organelles are
      involved in forming the TJ. Plasmodium falciparum and Toxoplasma gondii apical
      membrane antigen 1 (AMA-1) and rhoptry neck proteins (RONs) are the two main TJ
      components. It has been shown that RON4 plays an essential role during merozoite
      and sporozoite invasion to target cells. This study has focused on characterizing
      a novel Plasmodium vivax rhoptry protein, RON4, which is homologous to PfRON4 and
      PkRON4. METHODS: The ron4 gene was re-annotated in the P. vivax genome using
      various bioinformatics tools and taking PfRON4 and PkRON4 amino acid sequences as
      templates. Gene synteny, as well as identity and similarity values between open
      reading frames (ORFs) belonging to the three species were assessed. The gene
      transcription of pvron4, and the expression and localization of the encoded
      protein were also determined in the VCG-1 strain by molecular and immunological
      studies. Nucleotide and amino acid sequences obtained for pvron4 in VCG-1 were
      compared to those from strains coming from different geographical areas. RESULTS:
      PvRON4 is a 733 amino acid long protein, which is encoded by three exons, having
      similar transcription and translation patterns to those reported for its
      homologue, PfRON4. Sequencing PvRON4 from the VCG-1 strain and comparing it to P.
      vivax strains from different geographical locations has shown two conserved
      regions separated by a low complexity variable region, possibly acting as a
      "smokescreen". PvRON4 contains a predicted signal sequence, a coiled-coil alpha
      helical motif, two tandem repeats and six conserved cysteines towards the carboxy
      terminus and is a soluble protein lacking predicted transmembranal domains or a
      GPI anchor. Indirect immunofluorescence assays have shown that PvRON4 is
      expressed at the apical end of schizonts and co-localizes at the rhoptry neck
      with PvRON2. CONCLUSIONS: Genomic, transcriptional and expression data reported
      for PvRON4, as well as its primary structure characteristics suggest that this
      protein participates in reticulocyte invasion, as has been shown for its
      homologue PfRON4.

PMID- 24093779
TI  - The role of VariZIG in pregnancy.
AB  - Varicella infection during pregnancy is associated with serious maternal and
      fetal complications such as congenital varicella syndrome, maternal pneumonia and
      neonatal varicella. Pregnant women are ineligible to receive the varicella
      vaccination, thus women who lack evidence of immunity to varicella are at an
      increased risk for developing a varicella infection if exposed to a contagious
      individual. Presently, post-exposure prophylaxis involves the administration of a
      varicella zoster immunoglobulin (VariZIGTM) to prevent or reduce the severity of
      an infection. The US FDA recently approved VariZIG for licensure and recommend
      that it be administered as soon as possible following VZV exposure, ideally
      within 96 h for greatest effectiveness. The following review critically examines
      the role of VariZIG in post-exposure prophylaxis of varicella during pregnancy. 

PMID- 24093778
TI  - Inhalation of diesel exhaust does not exacerbate cardiac hypertrophy or heart
      failure in two mouse models of cardiac hypertrophy.
AB  - BACKGROUND: Strong associations have been observed between exposure to fine
      ambient particulate matter (PM2.5) and adverse cardiovascular outcomes. In
      particular, exposure to traffic related PM2.5 has been associated with increases
      in left ventricular hypertrophy, a strong risk factor for cardiovascular
      mortality. As much of traffic related PM2.5 is derived from diesel exhaust (DE),
      we investigated the effects of chronic DE exposure on cardiac hypertrophy and
      heart failure in the adult mouse by exposing mice to DE combined with either of
      two mouse models of cardiac hypertrophy: angiotensin II infusion or pressure
      overload induced by transverse aortic banding. METHODS: Wild type male C57BL/6 J
      mice were either infused with angiotensin II (800 ng/kg/min) via osmotic minipump
      implanted subcutaneously for 1 month, or underwent transverse aortic banding (27
      gauge needle 1 week for observing acute reactions, 26 gauge needle 3 months or 6
      months for observing chronic reactions). Vehicle (saline) infusion or sham
      surgery was used as a control. Shortly after surgery, mice were transferred to
      our exposure facility and randomly assigned to either diesel exhaust (300 or 400
      MUg/m(3)) or filtered air exposures. After reaching the end of designated time
      points, echocardiography was performed to measure heart structure and function.
      Gravimetric analysis was used to measure the ventricular weight to body weight
      ratio. We also measured heart rate by telemetry using implanted ambulatory ECG
      monitors. RESULTS: Both angiotensin II and transverse aortic banding promoted
      cardiac hypertrophy compared to vehicle or sham controls. Transverse aortic
      banding for six months also promoted heart failure in addition to cardiac
      hypertrophy. In all cases, DE failed to exacerbate the development of hypertrophy
      or heart failure when compared to filtered air controls. Prolonged DE exposure
      also led to a decrease in average heart rate. CONCLUSIONS: Up to 6-months of DE
      exposure had no effect on cardiac hypertrophy and heart function induced by
      angiotensin II stimulation or pressure overload in adult C57BL/6 J mice. This
      study highlights the potential importance of particle constituents of ambient
      PM2.5 to elicit cardiotoxic effects. Further investigations on particle
      constituents and cardiotoxicity are warranted.

PMID- 24093780
TI  - Interspecies correlation estimation-applications in water quality criteria and
      ecological risk assessment.

PMID- 24093781
TI  - Study on the antiulcer effects of Veronicastrum axillare on gastric ulcer in rats
      induced by ethanol based on tumor necrosis factor-alpha (TNF-alpha) and
      endothelin-1 (ET-1).
AB  - OBJECTIVE: To assess whether Veronicastrum axillare (V. axillare) can ameliorate
      ethanol-induced gastric mucosal lesions in rats, reduce the production of pro
      inflammatory cytokines, suppress apoptosis and improve local microcirculation
      disturbances. METHODS: Totally 48 male Sprague-Dawley rats were randomly divided
      into six groups, eight rats in each group. Rats in the normal group and the model
      group were administered with 0.9% normal saline respectively. Rats in the
      positive group and ranitidine group were administered with 0.18% ranitidine
      suspension by intragastric administration respectively. Those in the high dose V.
      axillare group, the medium dose V. axillare group and the low dose V. axillare
      group were administrated with V. axillare at the daily dose of 2.8 g/kg, 1.4 g/kg
      and 0.7 g/kg by intragastric administration. Gastric mucosal lesions were
      produced by intragastric administration of absolute ethanol. Water extract of V.
      axillare was successively injected for 14 d and last day was injected 1 h before
      ethanol administration. Gastric mucosal ulcer index and ulcer inhibitory rate
      were counted by improved Guth methods. The tissue sections were made for
      pathological histology analysis. Also, we measured the concentrations of tumor
      necrosis factor-alpha (TNF-alpha) and endothelin-1 (ET-1) in gastric mucosal, as
      an index of the pro-inflammatory cytokines, apoptosis and local microcirculation.
      Besides, the mRNA contents of TNF-alpha and ET-1 were measured to verify effects
      on gene expression by real-time fluorescent quantitative PCR. RESULTS: Water
      extract of V. axillare significantly ameliorated the gastric mucosal lesions
      induced by ethanol administration (P<0.01). Pro-inflammatory cytokines, TNF-alpha
      and ET-1 were increased after ethanol administration and significantly reduced by
      water extract of V. axillare. The expressions of TNF-alpha and ET-1 mRNA were
      also be inhibited by water extract of V. axillare. CONCLUSION: Current evidences
      show water extract of V. axillare is effective for defending against ethanol
      induced gastric mucosal lesions, significantly inhibiting the production of pro
      inflammatory cytokines and the expressions of TNF-alpha and ET-1 mRNA, which may
      be useful for inhibiting apoptosis and improving local microcirculation.

PMID- 24093782
TI  - Polymorphic patterns of pfcrt and pfmdr1 in Plasmodium falciparum isolates along
      the Thai-Myanmar border.
AB  - OBJECTIVE: To investigate the distribution and patterns of pfcrt and pfmdr1
      polymorphisms in Plasmodium falciparum (P. falciparum) isolates collected from
      the malaria endemic area of Thailand along Thai-Myanmar border. METHODS: Dried
      blood spot samples were collected from 172 falciparum malaria patients prior
      received treatment. The samples were extracted using chelex to obtain parasite
      DNA. PCR-RFLP was employed to detect pfcrt mutation at codons 76, 220, 271, 326,
      356 and 371, and the pfmdr1 mutation at codon 86. Pfmdr1 gene copy number was
      determined by SYBR Green I real-time PCR. RESULTS: Mutant alleles of pfcrt and
      wild type allele of pfmdr1 were found in almost all samples. Pfmdr1 gene copy
      number in isolates collected from all areas ranged from 1.0 to 5.0 copies and
      proportion of isolates carrying>1 gene copies was 38.1%. The distribution and
      patterns of pfcrt and pfmdr1 mutations were similar in P. falciparum isolates
      from all areas. However, significant differences in both number of pfmdr1 copies
      and prevalence of isolates carrying>1 gene copies were observed among isolates
      collected from different areas. The median pfmdr1 copy number in P. falciparum
      collected from Kanchanaburi and Mae Hongson were 2.5 and 2.0, respectively and
      more than half of the isolates carried>1 gene copies. CONCLUSIONS: The
      observation of pfmdr1 wild type and increasing of gene copy number may suggest
      declining of artesunate-mefloquine treatment efficacy in P. falciparum isolates
      in this border area.

PMID- 24093783
TI  - Screening and characterization of extracelluar L-asparaginase producing Bacillus
      subtilis strain hswx88, isolated from Taptapani hotspring of Odisha, India.
AB  - OBJECTIVE: To screen and isolate an eco-friendly, a thermophilic and potent L
      asparaginase producing bacterium, with novel immunological properties that may
      obviates hypersensitivity reactions. METHODS: In the present study bacterial
      strain isolated for extracellular L-asparaginase production from hotspring,
      identified by morphological, biochemical and physiological tests followed by 16S
      rDNA technology and the L-asparaginase production ability was tested by both semi
      quantitative and quantitative enzymatic assay. RESULTS: The bacterial strain was
      identified as Bacillus subtilis strain hswx88 (GenBank Accession Number:
      JQ237656.1). The extracellular enzyme yielding capacity isolate Bacillus subtilis
      strain hswx88 (23.8 IU/mL) was found to be 1.7 and 14.5 times higher than the
      reference organism Pectobacterium carotovorum MTCC 1428 (14.2 IU/mL) and Bacillus
      sp. BCCS 034 (1.64 IU/mL). CONCLUSION: The isolate is eco-friendly and useful to
      produce bulk quantity of extracellular, thermophilic L-asparaginase for the
      treatment of various tumor cases and for preparation of acrylamide free fry food
      preparation.

PMID- 24093785
TI  - Phytochemical, anti-oxidant and Anthelmintic activities of various leaf extracts
      of Flacourtia sepiaria Roxb.
AB  - OBJECTIVE: The present study was carried out to investigate the phytochemical
      constituents, In vitro antioxidant potential and anthelmintic activities of
      Flacourtia sepiaria Roxb leaves. METHODS: The dried powdered leaves of Flacourtia
      sepiaria were extracted using petroleum ether, chloroform, ethyl acetate and
      methanol by a soxhlet extractor and preliminary phytochemical screening was
      performed using standard protocols. All the extract was evaluated for their
      potential antioxidant activities using test such as DPPH, superoxide anion
      radical, hydroxyl radical, nitric oxide radical scavenging abilities, ferrous
      chelating ability and total phenolic and flavanoid content. Anthelmintic activity
      of extract was screened in adult Indian earthworm model. RESULTS: Preliminary
      screening revealed the presence of bioactive compounds especially phenolics,
      tannins and terpenoids in all extracts. The phenolic and flavanoid content was
      highest in methanolic extract and lowest in petroleum ether extract. The
      paralytic (9.46+/-0.212) and death time (31.43+/-0.148) of methanolic extract was
      found to be significant (P<0.05) when compared with paralytic (7.33+/-0.206) and
      death time (18.60+/-0.229) of standard piperazine citrate at 100 mg/mL
      concentration. CONCLUSIONS: The results of the present study indicate that the
      leaf extracts of Flacourtia sepiaria exhibited strong antioxidant activity and
      possess significant anthelmintic activity and thus it is a good source of
      antioxidant and anthelmintic constituents.

PMID- 24093784
TI  - Bacteriocin from Bacillus subtilis as a novel drug against diabetic foot ulcer
      bacterial pathogens.
AB  - OBJECTIVE: To isolate and identify Bacillus subtilis (B. subtilis) from soil and
      to characterize and partially purify the bacteriocin. To evaluate the
      antimicrobial activity against four diabetic foot ulcer bacterial pathogens.
      METHODS: Genotypic identification was done based on Bergey's manual of systemic
      bacteriology. Antimicrobial susceptibility test was done by Kirby-Bauer disc
      diffusion method. Colonies were identified by colony morphology and biochemical
      characterization and also compared with MTCC 121 strain. Further identification
      was done by 16S rRNA sequencing. Inhibitory activities of partially purified
      bacteriocin on all the DFU isolates were done by agar well diffusion method. The
      strain was identified to produce bacteriocin by stab overlay assay. Bacteriocin
      was extracted by organic solvent extraction using chloroform, further purified by
      HPLC and physical, and chemical characterization was performed. RESULTS: The four
      isolates showed high level of resistance to amoxyclav and sensitivity to
      ciprofloxacin. HPLC purification revealed that the extracts are bacteriocin. The
      phylogenetic tree analysis results showed that the isolate was 99% related to B.
      subtilis BSF01. The results reveled activity to all the four isolates and high
      level of activity was seen in case of Klebsiella sp. CONCLUSIONS: Partially
      purified bacteriocin was found to have antimicrobial activity against the four
      diabetic foot ulcer bacterial pathogens, which can thus be applied as a better
      drug molecule on further studies. The strain B. subtilis are found to be safe for
      use and these antimicrobial peptides can be used as an antimicrobial in humans to
      treat DFU bacterial pathogens.

PMID- 24093786
TI  - Inhibition of quorum sensing in Chromobacterium violaceum by Syzygium cumini L.
      and Pimenta dioica L.
AB  - OBJECTIVE: To investigated into the anti-quorum sensing (QS) activity of Syzygium
      cumini L. (S. cumini) and Pimenta dioica L. (P. dioica) using Chromobacterium
      violaceum (C. violaceum) strains. METHODS: In this study, anti-QS activity of
      ethanol extract of Syzygium cumini L. and Pimenta dioica L. were screened using
      C. violaceum CV026 biosensor bioassay. By bioassay guided fractionation of S.
      cumini and P. dioica, ethyl acetate fraction (EAF) with strong anti-QS activity
      was separated. Inhibition of QS regulated violacein production in C. violaceum
      ATCC12472 by EAF was assessed at different concentrations. The effect of EAF on
      the synthesis of autoinducer like N-acyl homoserine lactone (AHL) was studied in
      C. violaceum ATCC31532 using its mutant C. violaceum CV026 by standard methods.
      RESULTS: EAF inhibited violacein production in C. violaceum ATCC12472 in a
      concentration dependent manner without significant reduction in bacterial growth.
      Complete inhibition of violacein production was evidenced in 0.75-1.0 mg/mL
      concentration of EAF without inhibiting the synthesis of the AHL. TLC biosensor
      overlay profile of EAF revealed two translucent spots in S. cumini and P. dioica
      that inhibited C6-AHL mediated violacein production in C. violaceum CV026.
      CONCLUSIONS: This study indicates the anti-QS activity of the tested medicinal
      plants against C. violaceum.

PMID- 24093787
TI  - Analysis of phytochemical profile of Terminalia arjuna bark extract with
      antioxidative and antimicrobial properties.
AB  - OBJECTIVE: To investigate phytochemical screening, antimicrobial activity and
      qualitative thin layer chromatographic separation of flavonoid components,
      antioxidant activity and total flavonoid compound of Terminalia arjuna. METHODS:
      For phytochemical screening, some common and available standard tests were done.
      Antimicrobial bioassay was done through agar well diffusion method. Detection of
      antioxidant activity and flavonoid compounds were done through thin layer
      chromatography. Total antioxidant activity was measured by 2, 2-diphenyl-1
      picrylhydrazyl (DPPH) in colorimetric method. Aluminum chloride colorimetric
      method was used for total flavonoid determination. RESULTS: Phytochemical
      screening showed the active compounds presence in high concentration, such as
      phytosterol, lactones, flavonoids, phenolic compounds and tannins and glycosides.
      The antimicrobial activity of extract showed that greater inhibition zone against
      Gram negative bacteria than Gram positive bacteria. This methanolic extract
      showed a promising antioxidant activity, as absorption of DPPH redicles decreased
      in DPPH free radical scavenging assay. Flavonoids components having antioxidant
      property present in the methanol extract at a level of 199.00 mg quercetin
      equivalent/g of dried methanol extract in colorimetric method. CONCLUSIONS: The
      Terminalia arjuna bark extract revealed the presence of bio-active constituents
      which are known to exhibit medicinal as well as physiological activities.

PMID- 24093788
TI  - Pharmacological studies on Buchanania lanzan Spreng.- a focus on wound healing
      with particular reference to anti-biofilm properties.
AB  - OBJECTIVE: To evaluate the wound healing activity of the methanolic root extract
      of Buchanania lanzan Spreng. (B. lanzan), with a focus on antimicrobial and anti
      biofilm properties. METHODS: The extract was evaluated for its wound healing
      properties (excision and incision models) as evident from the analysis of tensile
      strength and wound contraction. The extract was also screened for antibacterial
      properties against different Gram positive and Gram negative bacterial strains.
      B. lanzan was also studied for its effect on biofilm formation and disruption of
      preformed biofilms. The synergistic effect of B. lanzan was determined in
      combination with gentamicin. RESULTS: Topical application of B. lanzan (10% w/w
      ointment) significantly increased (40.84%) the tensile strength in the incision
      wound model. B. lanzan also showed significant wound healing activity in excision
      model and such significant activity was observed from the 9th day. Whereas
      Soframycin displayed significant wound healing activity from the 6th day. It was
      found that root extracts of B. lanzan revealed significant inhibition against all
      tested pathogens. B. lanzan displayed antimicrobial activity against Gram
      positive (MIC 0.625 mg/mL) and Gram negative (MIC 0.625-1.25 mg/mL). B. lanzan
      was able to reduce biofilm formation and also caused disruption of preformed
      biofilms in a manner similar to ciprofloxacin. However, gentamicin was found to
      be ineffective against biofilms formed by Gram negative organism. According to
      the fractional inhibitory concentration index, B. lanzan displayed synergistic
      activity when it was combined with gentamicin. CONCLUSIONS: From this study it
      may be concluded that the root extract of B. lanzan revealed significant wound
      healing potential, which was supported and well correlated with pronounced
      antibacterial activity of the tested plant parts.

PMID- 24093789
TI  - A study on traditional medicinal plants of Uthapuram, Madurai District,
      Tamilnadu, South India.
AB  - OBJECTIVE: To record the medicinal plants of Uthapuram Village, Madurai district,
      Tamilnadu, South India for the first time and the usage of these medicinal plants
      to remediate the diseases among the peoples. METHODS: Explorative field trips
      were made to the village for about twelve months from April 2012 to May 2013 to
      survey the medicinal plants and collect the information from the villagers.
      RESULTS: From this study 52 species of valuable medicinal plants belonging to 36
      families were recorded and their ethnomedicinal values were collected from the
      village peoples. CONCLUSION: This study focuses the importance, utilization and
      conservation of the medicinal plants among the people.

PMID- 24093790
TI  - Control of human filarial vector, Culex quinquefasciatus Say 1823 (Diptera:
      Culicidae) through bioactive fraction of Cayratia trifolia leaf.
AB  - OBJECTIVE: To investigate the mosquito larvicidal activity of Cayratia trifolia
      (L.) Domin (Vitaceae: Vitales) (C. trifolia) which is distributed in many parts
      of India with medicinal properties as vector control is facing threat due to the
      emergence of resistance to synthetic insecticides. METHODS: Young and mature
      leaves of C. trifolia were investigated for larvicidal activity against 3rd
      instars larvae of Culex quinquefasciatus in different seasons throughout the
      year. The active fractions were extracted using six different solvents in a non
      polar to polar fashion viz petroleum-ether, benzene, chloroform: methanol (1:1
      v/v), acetone, absolute alcohol and distilled water. Dose dependent mortality was
      recorded against each solvent extract. Determination of LD50 and LD90 were
      executed through log-probit analysis using the most bioactive fraction. The
      fluctuations in mortality were statistically co-related through ANOVA analyses
      concerning different seasons and types of leaves as random variables.
      Justification of larvicidal activity was established through student's t-test.
      Costing effects were evaluated on the non-target water fauna under laboratory
      conditions. Thin layer chromatographic techniques were performed for
      phytochemical analysis and categorization of chemical personality of the active
      fractions using the most effective solvent extract following standard methods.
      RESULTS: Significant variations in mortality rate were noted with respect to the
      type of leaves (mature and senescence), concentration of leaf extract and between
      seasons. The water extract among all the solvent extracts was found to induce
      cent percent mortality at 50 mg/L in test mosquito species within 24 h with a
      LD50 and LD90 value of 10.70 mg/L and 27.64 mg/L respectively. No significant
      mortality was recorded in non-target water population. Chromatographic analyses
      of the water extract revealed the presence of steroids, triterpene glycosides,
      essential oil, phenolics and diterpenes as secondary phytochemicals. CONCLUSIONS:
      Water extract of C. trifolia leaf promised as a cost effective and potent
      larvicidal agent against Culex quinquefasciatus.

PMID- 24093791
TI  - Chemical profiling of Elaeocarpus serratus L. by GC-MS.
AB  - OBJECTIVE: To determine the possible bioactive components of the ethanolic
      extract of leaves of Elaeocarpus serratus (E. serratus). METHODS: The present
      research was carried out by using GC-MS analysis, while mass spectra of the
      compounds found in the extract was matched with the National Institute of
      Standards and Technology and Wiley library. RESULTS: Thirty components from
      leaves of the above said plant were identified. The active principles with their
      retention time, molecular formula, molecular weight and concentration (%) in the
      ethanol extracts of leaf of E. serratus are obtained. CONCLUSIONS: This is the
      first report of documentation of active constituents from leaves of E. serratus.
      The research reveals the potential of E. serratus leaves as a good source of
      bioactive compounds such as fatty acid esters, alcohols, hydrocarbons, aldehydes,
      alkenes, fatty acids and amides that justify the use of this plant for its
      various ailments by traditional practitioners.

PMID- 24093792
TI  - Bacteriological and pathological studies of egg peritonitis in commercial layer
      chicken in Namakkal area.
AB  - OBJECTIVE: To detect the various bacteriological agents and pathological changes
      in commercial layer chicken affected with egg yolk peritonitis in Namakkal region
      of India. METHODS: A total of 6 572 layer chicken from 85 commercial farms were
      subjected for the study, out of which 1 715 showed various types of oviduct
      abnormalities. Among the 1 715, 264 birds from six farms were identified as egg
      peritonitis on the basis of postmortem examination. Trachea, lung, heart blood,
      liver, peritoneal exudate, oviduct (infundibulum, magnum, uterus) and cloacal
      swabs were collected from the 264 birds with egg peritonitis lesion for screening
      of bacterial agents. Signalment, clinical signs and pathological changes were
      recorded in the affected flocks. RESULTS: The results of the present
      investigation indicated that the E. coli associated egg peritonitis was
      responsible for 15.39% of the reproductive tract abnormalities in commercial
      layers between 21 and 80 week of age. In the affected flocks egg production drop
      and mortality varied from 3% to 20% and 0.5% to 7.0% respectively. It was noticed
      during peak egg production (21 to 60 week) and southwest monsoon season (58%).
      Statistical analysis of age, season and egg production by Chi square test of
      independence revealed highly significant difference. E. coli was isolated as a
      pure culture and concurrent with other bacterial agents in 226 and 38 birds
      respectively. Among the fifteen E. coli serotypes identified serotype O166, O64
      and O111 were predominant. Necropsy examination of affected birds revealed the
      presence of amorphous or insipissiated yolk material in the abdominal cavity with
      inflammatory changes in the ovary, oviduct and intestine. Microscopically the
      oviduct surface epithelium showed degeneration and desquamation, moderate to
      marked infiltration of inflammatory cells especially heterophils and lymphocytes
      in various regions and lumen contained serofibrinous exudate, inflammatory and
      desquamated epithelial cells with bacterial microcolonies. Ovarian follicles
      revealed hyperemia, degeneration of granulosa cells and infiltration of
      inflammatory cells. Intestine showed degenerative, necrotic and inflammatory
      lesion. CONCLUSION: The findings of this study showed that the egg peritonitis
      might be caused by either the translocation of intestinal E. coli into the
      peritoneal cavity or by the movement of cloacal E. coli into the oviduct followed
      by ascension of these bacteria up the oviduct, through the infundibulum, and into
      the peritoneal cavity. To control the egg peritonitis faecal contamination with
      E. coli should be minimized.

PMID- 24093793
TI  - Formulation of unidirectional release buccal patches of carbamazepine and study
      of permeation through porcine buccal mucosa.
AB  - OBJECTIVE: To achieve transbuccal release of carbamazepine by loading in
      unidirectional release mucoadhesive buccal patches. METHODS: Buccal patches of
      carbamazepine with unidirectional drug release were prepared using hydroxypropyl
      methyl cellulose, polyvinyl alcohol, polyvinyl pyrrolidone and ethyl cellulose by
      solvent casting method. Water impermeable backing layer (Pidilite(r) Biaxially
      oriented polypropylene film) of patches provided unidirectional drug release.
      They were evaluated for thickness, mass uniformity, surface pH and folding
      endurance. Six formulations FA2, FA8, FA10, FB1, FB14 and FB16 (folding endurance
      above 250) were evaluated further for swelling studies, ex vivo mucoadhesive
      strength, ex vivo mucoadhesion time, In vitro drug release, ex vivo permeation,
      accelerated stability studies and FTIR and XRD spectral studies. RESULTS: The ex
      vivo mucoadhesion time of patches ranged between 109 min (FA10) to 126 min
      (FB14). The ex vivo mucoadhesive force was in the range of 0.278 to 0.479 kg/m/s.
      The In vitro drug release studies revealed that formulation FA8 released 84% and
      FB16 released 99.01% of drug in 140 min. CONCLUSIONS: The prepared unidirectional
      buccal patches of carbamazepine provided a maximum drug release within specified
      mucoadhesion period and it indicates a potential alternative drug delivery system
      for systemic delivery of carbamazepine.

PMID- 24093794
TI  - Some ecological attributes of malarial vector Anopheles superpictus Grassi in
      endemic foci in southeastern Iran.
AB  - OBJECTIVE: To determine the bionomics and susceptibility status of the malarial
      vector Anopheles superpictus (An. superpictus) to different insecticides in the
      Sistan-Baluchestan province which has the highest malarial prevalence in Iran.
      METHODS: Different sampling methods, in addition to scoring abdominal conditions,
      were used to define the seasonal activity and endo/exophilic behavior of this
      species. In addition, the standard WHO susceptibility tests were applied on adult
      field strains. RESULTS: Most adult mosquitoes were collected from outdoor
      shelters. The peak of seasonal activity of An. superpictus occurred at the end of
      autumn. Most larvae were collected from natural and permanent breeding places
      with full sunlight and no vegetation. Blood feeding activities occurred around
      midnight. Compared with the abdominal conditions of adult mosquitoes collected
      indoors, the abdominal conditions of adult mosquitoes collected outdoors were
      gravid and semigravid. This species was suspected to be resistant to DDT, but was
      susceptible to other insecticides. CONCLUSIONS: An. superpictus was present in
      almost all outdoor shelters, and the ratios of gravid, semigravid/unfed, and
      freshly fed confirmed that this species had a higher tendency to rest outdoors
      than indoors. This behavior can protect An. superpictus from indoor residual
      spraying in this malarious area. To the best of our knowledge, this is the first
      report on the susceptibility status of An. superpictus in Southeastern Iran. We
      do not suggest the use of DDT for indoor residual spraying in southeast Iran.

PMID- 24093795
TI  - Plant profile, phytochemistry and pharmacology of Cordia dichotoma (Indian
      cherry): a review.
AB  - More than half of the world's population relies on the traditional medicine and
      major role of the traditional medicine including the use of plant extract and
      their active constituents. Among them, Cordia dichotoma Forst., a small to
      moderate size plant of family Boragenaceae, commonly called bhokar, lasura,
      gonda, Indian cherry and shlesmataka. Plant parts such as leaves, fruit, bark and
      seed have been reported for possessing antidiabetic, antiulcer, anti
      inflammatory, immune-modulator and analgesic activity. Screening of fruit, leaves
      and seed shows the presence of pyrrolizidine alkaloids, coumarins, flavonoids,
      saponins, terpenes and sterols. Present review focuses on details of geographical
      distribution, physicochemical parameters, phytoconstituents and pharmacological
      properties of Cordia dichotoma reported so far. 

PMID- 24093796
TI  - Cancer burden in China: a Bayesian approach.
AB  - BACKGROUND: Cancer is a serious health issue in China, but accurate national
      counts for cancer incidence are not currently available. Knowledge of the cancer
      burden is necessary for national cancer control planning. In this study, national
      death survey data and cancer registration data were used to calculate the cancer
      burden in China using a Bayesian approach. METHODS: Cancer mortality and
      incidence rates for 2004-2005 were obtained from the National Cancer Registration
      database. The third National Death Survey (NDS), 2004-2005 database provided
      nationally representative cancer mortality rates. Bayesian modeling methods were
      used to estimate mortality to incidence (MI) ratios from the registry data and
      national incidence from the NDS for specific cancer types by age, sex and urban
      or rural location. RESULTS: The total estimated incident cancer cases in 2005
      were 2,956,300 (1,762,000 males, 1,194,300 females). World age standardized
      incidence rates were 236.2 per 100,000 in males and 168.9 per 100,000 in females
      in urban areas and 203.7 per 100,000 and 121.8 per 100,000 in rural areas.
      CONCLUSIONS: MI ratios are useful for estimating national cancer incidence in the
      absence of representative incidence or survival data. Bayesian methods provide a
      flexible framework for smoothing rates and representing statistical uncertainty
      in the MI ratios. Expansion of China's cancer registration network to be more
      representative of the country would improve the accuracy of cancer burden
      estimates.

PMID- 24093797
TI  - Rapid determination of lovastatin in the fermentation broth of Aspergillus
      terreus using dual-wavelength UV spectrophotometry.
AB  - CONTEXT: Lovastatin, a hypocholesterolemic drug, is produced by submerged
      fermentation of Aspergillus terreus Thom (Trichocomaceae). High performance
      liquid chromatography is usually used to determine lovastatin in samples of the
      fermentation broth. However, this method is inconvenient and costly, especially
      in the context of high-throughput sample analysis. OBJECTIVE: A direct and simple
      dual-wavelength ultraviolet spectrophotometric method for quantifying lovastatin
      in the fermentation broth of A. terreus was developed. MATERIALS AND METHODS: A.
      terreus Z15-7 was used for all experiments. The liquid fermentation was conducted
      at 30  degrees C in a rotary shaker at 150 rpm for 15 d. Silica gel and neutral
      alumina column chromatography were used for the separation and purification of
      lovastatin from the fermentation broth. RESULTS: The limits of detection of
      lovastatin were 0.320 MUg/ml in the lovastatin standard solution and 0.490 MUg/ml
      in the fermentation broth sample and the limits of quantification of lovastatin
      were 1.265 MUg/ml in the lovastatin standard solution and 3.955 MUg/ml in the
      fermentation broth sample. The amounts of lovastatin in the fermentation broth
      ranged from 876.614 to 911.967 MUg/ml, with relative standard deviations from
      1.203 to 1.709%. The mean recoveries of lovastatin using silica gel and neutral
      alumina column chromatography were 84.2 +/- 0.82 and 87.2 +/- 0.21%,
      respectively. DISCUSSION AND CONCLUSION: Dual-wavelength UV spectrophotometry is
      a rapid, sensitive, accurate, and convenient method for quantifying lovastatin in
      fermentation broth. Neutral alumina column chromatography is more efficient than
      silica gel column chromatography for the purification and determination
      lovastatin using the developed dual-wavelength UV spectrophotometry method.

PMID- 24093798
TI  - "She is my teacher and if it was not for her I would be dead": exploration of
      rural South African community health workers' information, education and
      communication activities.
AB  - Community health workers (CHWs) are important resources in health systems
      affected by the HIV/AIDS pandemic. International guidelines on task-shifting
      recommend that CHWs can provide diverse HIV services, ranging from HIV prevention
      to counselling patients for lifelong antiretroviral therapy. There is, however,
      little evidence on the experiences with CHW delivery of these services in Africa.
      This qualitative study included 102 interviews that explored experiences with
      information, education and communication (IEC) activities provided by CHWs within
      rural South Africa. Semi-structured interviews were conducted with CHWs (n = 17),
      their clients (n = 33) and the primary caregivers of these clients (n = 30),
      allowing for data source triangulation. Twenty-two follow-up interviews explored
      emergent themes from preliminary interviews. Despite limited formal education and
      training, CHWs in this study were significant providers of IEC, including
      provision of generic health talks and HIV-specific information and facilitation
      to support clients' entry and maintenance in the formal health system. They often
      incorporated local knowledge and understanding of illness in their communication.
      CHWs in this study were able to bridge the lifeworlds of the community and the
      formal services to expedite access and adherence to local clinics and other
      services. As mediators between the two worlds, CHWs reinterpreted health
      information to make it comprehensible in their communities. With growing
      formalisation of CHW programmes in South Africa and elsewhere, CHWs' important
      role in health service access, health promotion and health maintenance must be
      recognised and supported in order to maximise impact. 

PMID- 24093799
TI  - Th1 and Th17 but no Th2-related cytokine spectrum in the cerebrospinal fluid of
      children with Borrelia-related facial nerve palsy.
AB  - BACKGROUND: Chemokines and cytokines in cerebrospinal fluid (CSF) and serum have
      been extensively studied in adults with neuroborreliosis (NB), whereas there are
      limited data about the pediatric population. In adults, T helper type 1 (Th1) and
      Th17-related cytokines were observed during acute NB. In children, the Th2
      response is thought to moderate the disease course. The aim of this study was to
      determine the chemokine-cytokine profile in children with acute NB displaying
      Borrelia-related peripheral facial nerve palsy (PFNP). METHODS: Luminex multiple
      bead technology was used for the detection of twelve cytokines and chemokines in
      the CSF and serum of three groups: 1) children with Borrelia-related PFNP
      (BPFNP); 2) children with non-borrelial "idiopathic" PFNP (NIPFNP); and 3) age
      related controls. RESULTS: In BPFNP, cytokines-chemokines related to a non
      specific pro-inflammatory activity and specific Th1/Th17 responses were detected
      in CSF, and elevated IL-7 and IL-10 levels were observed in serum and CSF
      compared to NIPFNP and to controls. In NIPFNP, CSF findings were similar to
      controls; however, higher levels of IL-7 and MCP-1 were observed in serum. Higher
      IL-8, IL-15 and MCP-1 levels were detected in CSF compared to serum in all
      groups. MCP-1 and IL-8 levels in CSF were strikingly higher in BPFNP compared to
      the other two groups, while IL-15 levels in CSF showed no difference. In
      addition, in controls, increased IL-4 level was found in CSF compared to serum.
      CONCLUSION: The chemokine-cytokine profile in the CSF of children with acute NB
      was similar to previous studies in adults. Our data suggests that higher levels
      of IL-4, IL-15 and MCP-1 levels in CSF compared to serum in controls might
      represent a potentially protective cytokine milieu in the CNS compartment.

PMID- 24093801
TI  - Serotonin transporter (5-HTT) gene polymorphisms and susceptibility to epilepsy:
      a meta-analysis and meta-regression.
AB  - AIMS: Serotonin transporter (5-HTT) plays a central role in the regulation of
      serotonin (5-hydroxytryptamine [5-HT]) synaptic function. Disturbances in 5-HT
      transmission are the most frequently reported neurobiological substrates of
      suicidal behavior. Emerging evidence has shown that the common polymorphisms in
      the 5-HTT gene may contribute to the risk of epilepsy, but individually published
      studies showed inconclusive results. This meta-analysis aimed to derive a more
      precise estimation of the associations between 5-HTT gene polymorphisms and
      susceptibility to epilepsy. METHODS: A literature search of PubMed, Embase, Web
      of Science, and China BioMedicine (CBM) databases was conducted on articles
      published before June 1st, 2013. Crude odds ratios with 95% confidence intervals
      were calculated. RESULTS: Seven studies were assessed with a total 1303 epilepsy
      patients and 1288 healthy controls. The meta-analysis results indicated that
      there was no significant relationship between 5-HTT gene polymorphisms and an
      increased risk of epilepsy. Further subgroup analysis based on ethnicity also
      found no significant association between 5-HTT gene polymorphisms and epilepsy
      risk among both Caucasian and Asian populations. In addition, there was also no
      significant association between 5-HTT gene polymorphisms and the risk of
      psychiatric comorbidity in patients with epilepsy. CONCLUSION: In conclusion, the
      current meta-analysis indicates that 5-HTT gene polymorphisms might not be the
      primary determinants of epilepsy susceptibility. 5-HTT genes might be expected to
      interact with other genes in different signaling pathways to initiate and promote
      the epileptogenic process.

PMID- 24093800
TI  - Transcriptome analysis of heat stress response in switchgrass (Panicum virgatum
      L.).
AB  - BACKGROUND: Global warming predictions indicate that temperatures will increase
      by another 2-6 degrees C by the end of this century. High temperature is a major
      abiotic stress limiting plant growth and productivity in many areas of the world.
      Switchgrass (Panicum virgatum L.) is a model herbaceous bioenergy crop, due to
      its rapid growth rate, reliable biomass yield, minimal requirements of water and
      nutrients, adaptability to grow on marginal lands and widespread distribution
      throughout North America. The effect of high temperature on switchgrass
      physiology, cell wall composition and biomass yields has been reported. However,
      there is void in the knowledge of the molecular responses to heat stress in
      switchgrass. RESULTS: We conducted long-term heat stress treatment (38 degrees
      /30 degrees C, day/night, for 50 days) in the switchgrass cultivar Alamo. A
      significant decrease in the plant height and total biomass was evident in the
      heat stressed plants compared to controls. Total RNA from control and heat stress
      samples were used for transcriptome analysis with switchgrass Affymetrix
      genechips. Following normalization and pre-processing, 5365 probesets were
      identified as differentially expressed using a 2-fold cutoff. Of these, 2233
      probesets (2000 switchgrass unigenes) were up-regulated, and 3132 probesets (2809
      unigenes) were down-regulated. Differential expression of 42 randomly selected
      genes from this list was validated using RT-PCR. Rice orthologs were retrieved
      for 78.7% of the heat stress responsive switchgrass probesets. Gene ontology
      (GOs) enrichment analysis using AgriGO program showed that genes related to
      ATPase regulator, chaperone binding, and protein folding was significantly up
      regulated. GOs associated with protein modification, transcription, phosphorus
      and nitrogen metabolic processes, were significantly down-regulated by heat
      stress. CONCLUSIONS: Plausible connections were identified between the identified
      GOs, physiological responses and heat response phenotype observed in switchgrass
      plants. Comparative transcriptome analysis in response to heat stress among four
      monocots - switchgrass, rice, wheat and maize identified 16 common genes, most of
      which were associated with protein refolding processes. These core genes will be
      valuable biomarkers for identifying heat sensitive plant germplasm since they are
      responsive to both short duration as well as chronic heat stress treatments, and
      are also expressed in different plant growth stages and tissue types.

PMID- 24093802
TI  - Functional polymorphisms in surfactant protein genes and chronic obstructive
      pulmonary disease risk: a meta-analysis.
AB  - AIMS: Increasing scientific evidence suggests that functional polymorphisms in
      surfactant protein (SP) genes may contribute to increasing susceptibility to
      chronic obstructive pulmonary disease (COPD), but many existing studies have
      yielded inconclusive results. This meta-analysis aims to assess the exact role of
      SP gene polymorphisms in the development of COPD. METHODS: An extensive
      literature search for relevant studies was conducted on PubMed, Embase, Web of
      Science, Cochrane Library, and CBM databases from their inception through May
      1st, 2013. This meta-analysis was performed using the STATA 12.0 software. The
      crude odds ratio (OR) with 95% confidence interval (CI) were calculated. RESULTS:
      Seven case-control studies were included with a total of 2761 subjects, including
      1274 COPD cases and 1482 healthy controls. Our meta-analysis revealed that common
      polymorphisms in the SP-A gene may be associated with an increased risk of COPD
      (allele model: OR=1.53, 95% CI: 1.14-2.05, p=0.005; dominant model: OR=1.65, 95%
      CI: 1.02-2.69, p=0.043; recessive model: OR=1.66, 95% CI: 1.17-2.35, p=0.005;
      homozygous model: OR=2.06, 95% CI: 1.24-3.41, p=0.005; heterozygous model:
      OR=1.59, 95% CI: 1.13-2.22, p=0.007), especially among Asian populations.
      However, there was no evidence for any association between common polymorphisms
      in the SP-B and SP-D genes and COPD risk (all p>0.05). CONCLUSION: The current
      meta-analysis indicates that common polymorphisms in the SP-A gene may contribute
      to increasing susceptibility to COPD, especially among Asian populations.

PMID- 24093803
TI  - Association of XPC gene polymorphisms with susceptibility to prostate cancer:
      evidence from 3,936 subjects.
AB  - AIM: Polymorphisms of xeroderma pigmentosum complementation group C (XPC) are
      thought to have significant effects on prostate cancer (PCa) risk. The aim of our
      study was to evaluate the impact of XPC gene polymorphisms on PCa risk by using a
      meta-analysis. METHODS: Data were collected from the following electronic
      databases: PubMed, EMBASE, Elsevier Science Direct, Cochrane Library, and CNKI,
      with the last report up to April 30, 2013. Odds ratios with 95% confidence
      intervals were used to assess the strength of the association. RESULTS: A total
      of five separate case-control studies (1966 cases and 1970 controls) were
      included in this meta-analysis. Meta-analysis was performed for the rs2228001 and
      PAT+/-polymorphisms. We did not detect a significant association between
      rs2228001 polymorphism and PCa (p>0.05). Similar results were found in
      stratification analyses by ethnicity and tumor stage. We detected a significant
      association of PAT+/-polymorphism with PCa (p<0.05). In stratification analysis,
      we did not detect a significant association of PAT+/-polymorphism with risk of
      bone metastasis in PCa patients (p>0.05). CONCLUSION: These analyses suggest that
      XPC gene PAT+/-polymorphism, but not rs2228001, likely contributes to
      susceptibility to PCa.

PMID- 24093804
TI  - Conservation and functional importance of carbon-oxygen hydrogen bonding in
      AdoMet-dependent methyltransferases.
AB  - S-adenosylmethionine (AdoMet)-based methylation is integral to metabolism and
      signaling. AdoMet-dependent methyltransferases belong to multiple distinct
      classes and share a catalytic mechanism that arose through convergent evolution;
      however, fundamental determinants underlying this shared methyl transfer
      mechanism remain undefined. A survey of high-resolution crystal structures
      reveals that unconventional carbon-oxygen (CH...O) hydrogen bonds coordinate the
      AdoMet methyl group in different methyltransferases irrespective of their class,
      active site structure, or cofactor binding conformation. Corroborating these
      observations, quantum chemistry calculations demonstrate that these charged
      interactions formed by the AdoMet sulfonium cation are stronger than typical
      CH...O hydrogen bonds. Biochemical and structural studies using a model lysine
      methyltransferase and an active site mutant that abolishes CH...O hydrogen
      bonding to AdoMet illustrate that these interactions are important for high
      affinity AdoMet binding and transition-state stabilization. Further,
      crystallographic and NMR dynamics experiments of the wild-type enzyme demonstrate
      that the CH...O hydrogen bonds constrain the motion of the AdoMet methyl group,
      potentially facilitating its alignment during catalysis. Collectively, the
      experimental findings with the model methyltransferase and structural survey
      imply that methyl CH...O hydrogen bonding represents a convergent evolutionary
      feature of AdoMet-dependent methyltransferases, mediating a universal mechanism
      for methyl transfer.

PMID- 24093805
TI  - A novel glucose/pH responsive low-molecular-weight organogel of easy recycling.
AB  - A new phenylboronic acid based gelator was developed to prepare low-molecular
      weight organogel (LMOG), which could interact with several solvents to assemble
      into a three-dimensional nanofiber network. (1)H NMR spectroscopy study suggests
      that the driving force for the gelation includes hydrogen bonding and pi-pi
      stacking. Evaluated by UV-spectroscopy, the gel showed a prompt initial response
      to glucose at low concentration of 0.012 mmol/mL, which is a critical
      concentration of venous plasma glucose for diabetes. Significantly, this
      organogel exhibits excellent sensitivity to glucose among seven sugars tested
      (i.e., mannitol, galactose, lactose, maltose, sucrose, and fructose). The
      proposed formation of hydrogen-bonded complexes during the glucose sensing was
      supported by our energy calculation. Meanwhile, this organogel exhibits pH
      response. Importantly, this LMOG could be conveniently recycled and thus be
      reused. 

PMID- 24093806
TI  - Inhaler technique and patient's preference for dry powder inhaler devices.
AB  - Inhaled therapy has a central place in the management of obstructive lung
      diseases, but a large number of patients are unable to use their inhalers
      correctly with a consequent reduction in therapeutic benefit. Correct use of
      inhalers is, therefore, crucial for efficient therapy, and acceptance of the
      device can improve patients' compliance. The choice of the most appropriate
      inhaler for a given patient is often not straightforward. The ease-of-use and
      performance characteristics of the inhaler will markedly influence patients'
      acceptance of the device, as well the patients' attitudes to their illness and
      chronic medication use in general. Choosing the most appropriate inhaler for a
      specific patient and regular assessment of ability to correctly use their inhaler
      will promote better adherence to therapy with improved disease outcome. Further,
      patients' preference for a particular inhaler should be taken into consideration.
      In patients with obstructive airway diseases, inhaler choice is as critical as
      the choice of medication itself. 

PMID- 24093807
TI  - Structures and absolute configurations of penicillactones A-C from an endophytic
      microorganism, Penicillium dangeardii Pitt.
AB  - Penicillactones A-C (1-3) are structurally related natural products with a
      spirocyclic anhydride structure and were isolated from the endophytic fungus
      Penicillium dangeardii Pitt. Penicillactones B and C showed inhibition of the
      release of beta-glucuronidase from polymorphonuclear leukocytes with ED50 values
      of 2.58 and 1.57 MUM. A 2D INADEQUATE experiment of 1 was performed at natural
      abundance to confirm the arrangement of its carbon skeleton. The configurations
      of 1-3 were established through extensive NMR spectroscopic analysis, selective
      structural modifications, and CD analysis. 

PMID- 24093808
TI  - Tropical tannin-rich fodder intake modifies saliva-binding capacity in growing
      sheep.
AB  - We evaluated the effect of feeding dietary tannins from Lysiloma latisiliquum
      fresh forage on the saliva tannin-binding capacity of hair sheep lambs without
      previous exposure to tannin-rich (TR) fodder. Twenty-four hair sheep lambs
      (13.6+/-3.04 kg LW) were fed a tannin-free diet at the beginning of the
      experimental period (from day 10 to 13). On day 14, lambs were distributed into
      three groups (n=8): control group (CG), fed with the tannin-free diet (from D10
      to D112); tannin short-term group (TST), fed the basal diet and 650 g of L.
      latisiliquum forage (from D14 to D55); tannin long-term group (TLT), fed the
      basal diet and 650 g of L. latisiliquum forage (from D14 to D112). Saliva samples
      were collected from the mouth of each lamb in the morning before feeding time on
      D10 and D14 (baseline period), on D49 and D56 (period 1) and on D97 and D112
      (period 2). The tannin binding response of salivary protein (?% turbidity) was
      determined with the haze development test (HDT) using either tannic acid or L.
      latisiliquum forage acetone extract. A turbidity protein index (TPI) was
      calculated as (?% turbidity/[salivary protein (mg)]). Differences in HDT and TPI
      in the different groups were compared by repeated measures ANOVA using Proc
      Mixed. All groups had similar ?% turbidity throughout the experiment (P>0.05). At
      baseline and period 1, the TPI of the different groups was similar (P>0.05). On
      period 2 the TLT group showed higher TPI compared with CG (P<0.05). Meanwhile, CG
      and TST showed similar salivary TPI. The saliva of hair sheep lambs consuming TR
      L. latisiliquum fresh fodder (TLT group) increased their TPI compared with
      control lambs not exposed to tannins. 

PMID- 24093809
TI  - Participant experiences and facilitators and barriers to pill use among men who
      have sex with men in the iPrEx pre-exposure prophylaxis trial in San Francisco.
AB  - In 2010, the iPrEx study demonstrated efficacy of daily emtricitabine/tenofovir
      disoproxil fumarate (FTC/TDF) pre-exposure prophylaxis (PrEP) in reducing HIV
      acquisition among men who have sex with men. Adherence to study product was
      critical for PrEP efficacy, and varied considerably, with FTC/TDF detection rates
      highest in the United States. We conducted a qualitative study to gain insights
      into the experiences of iPrEx participants in San Francisco (SF) where there was
      high confirmed adherence, to understand individual and contextual factors
      influencing study product use in this community. In 2009 and 2011, we conducted
      focus groups and in-depth interviews in 36 and 16 SF iPrEx participants,
      respectively. Qualitative analyses indicate that participants joined the study
      out of altruism. They had a clear understanding of study product use, and pill
      taking was facilitated by establishing or building on an existing routine.
      Participants valued healthcare provided by the study and relationships with
      staff, whom they perceived as nonjudgmental, and found client-centered counseling
      to be an important part of the PrEP package. This facilitated pill taking and
      accurate reporting of missed doses. Adherence barriers included changes in
      routine, side effects/intercurrent illnesses, and stress. Future PrEP adherence
      interventions should leverage existing routines and establish client-centered
      relationships/ environments to support pill taking and promote accurate
      reporting.

PMID- 24093810
TI  - Stages of change for adherence to antiretroviral medications.
AB  - Providers do not predict reliably which of their HIV-positive patients are having
      difficulty adhering to antiretroviral therapy (ART). The transtheoretical, or
      stages of change model, may be a useful tool to help providers identify patients
      who are having difficulty with ART adherence. The objective of the current study
      was to determine the relationship between stages of change and ART adherence
      among patients who were actively taking ART. Data from a randomized trial of a
      provider-focused intervention were used to examine the relationship between the
      stages of change and adherence, measured using electronic monitoring devices in
      the 30 days following the stages of change assessment. Individuals were eligible
      for inclusion if they were taking ART and had detectable plasma viral load (HIV
      RNA). Repeated measures analysis of covariance was used to determine the impact
      of stages of change on adherence after controlling for potential confounders. The
      sample of 137 participants was 22% female, 48% white, 28% African-American, with
      a mean age of 42 years. Fifty-eight percent reported sex with a man as an HIV
      risk factor, while 13% reported sex with a woman, 14% reported injecting drugs
      and 15% reported other risk factors. In adjusted models, those in earlier stages
      of change (i.e., contemplation and preparation) had significantly lower adherence
      (-9.8%, p=0.04) compared to those in the action and maintenance phases. No
      demographic characteristics predicted adherence. The stages of change model may
      function as a screening tool for clinicians to discover patients at-risk of lower
      adherence.

PMID- 24093811
TI  - Is self-perceived HIV risk congruent with reported HIV risk among traditionally
      lower HIV risk and prevalence adult emergency department patients? Implications
      for HIV testing.
AB  - Because reliance on patients' self-perceived risk for HIV might mislead emergency
      department (ED) clinicians on the need for HIV testing, we aimed to measure
      congruency between self-perceived and reported HIV risk in a traditional lower
      prevalence, lower-risk cohort. A random sample of 18- to 64-year-old patients at
      a large academic urban ED who were by self-report not men-who-have-sex-with-men
      (MSM) or injection-drug users (IDUs) were surveyed regarding their self-perceived
      and reported HIV risk. Sixty-two percent of participants were white non-Hispanic,
      13.8% Black, and 21.2% Hispanic; and 66.9% previously had been tested for HIV.
      Linear regression models were constructed comparing self-perceived to reported
      HIV risk. Among the 329 female ED patients, 50.5% perceived that they were "not
      at risk" for HIV, yet only 10.9% reported no HIV risk behaviors, while among the
      175 male ED patients, 50.9% perceived that they were "not at risk" for HIV, yet
      only 12.6% reported no HIV risk behaviors. Only 16.9% of women and 15.7% of men
      who had no self-perceived risk for HIV also reported no HIV risk behaviors.
      Multivariable linear regression demonstrated a weak relationship between self
      perceived and reported risk. Congruency between self-perceived risk and reported
      HIV risk was low among these non-MSM, non-IDU ED patients.

PMID- 24093813
TI  - Sleep quantity and quality in elite youth soccer players: a pilot study.
AB  - This study examined the effect of early evening high-intensity training on the
      sleep of elite male youth soccer players (n = 12) using wrist actigraphy. High
      intensity training (TRAIN) nights were compared with a home environment (HOME)
      condition, created by averaging sleep variables on the night before and after
      TRAIN nights. Additionally, after TRAIN athletes alternately used cold water
      immersion (TRAIN+CWI) or none, to assess whether cold water immersion (CWI) had
      any impact on sleep quality and quantity. Ratings of perceived exertion, fatigue
      and recovery were recorded after training. Actigraphy sleep measures were
      bedtime, wake time, sleep duration, sleep onset latency, sleep efficiency and
      wake after sleep onset. Self-rated scores of sleepiness at bedtime and wake, plus
      overall sleep quality were also recorded. Only fatigue ratings were higher in
      TRAIN compared to TRAIN+CWI at bedtime, there were no other differences in
      training data. Both TRAIN and TRAIN+CWI conditions had significant later (07:45
      +/- 1:09 h p < 0.01 and 07:34 +/- 1:20 h p = 0.01) wake times than HOME (06:44 +/
      0:41 h). The TRAIN condition had a significantly higher (7 +/- 2; p < 0.01)
      rating of sleepiness at bedtime compared to HOME (6 +/- 1), but no further
      differences were found in any of the sleep (actigraphy and self-reported)
      measures. Across all conditions, time spent asleep was ~7:30 (+/-0:52) h:min and
      sleep efficiency was ~89% (+/-6.1). In conclusion, early evening high-intensity
      training had no impact on subsequent sleep quality and quantity, nor was there
      any effect on sleep after performing CWI post-training. 

PMID- 24093814
TI  - Novel mutations in the TAZ gene in patients with Barth syndrome.
AB  - Barth syndrome is an X-linked recessive disorder that is caused by mutations in
      Taffazin gene (TAZ), leading to severe cardiolipin deficiency which results in
      respiratory chain dysfunction. Barth syndrome is characterized by cardiomyopathy,
      neutropenia, skeletal myopathy, growth deficiency and 3-methylglutaconic
      aciduria. In this paper, we present clinical, biochemical and molecular data of
      the first four Czech patients from four unrelated families diagnosed with this
      rare disease. The mean age of onset was 5.5 +/- 3.8 months. One child suffered
      from sudden cardiac death at the age of 2 years, the age of living patients is
      between 3 and 13 years. Muscle hypotonia was present in all four patients;
      cardiomyopathy and growth retardation in three and neutropenia in two of them.
      Two patients manifested a dilated and one patient a hypertrophic cardiomyopathy.
      A characteristic laboratory abnormality was the intermittently increased
      excretion of 3-methylglutaconic acid. Three novel hemizygous mutations in the TAZ
      gene were found (c.584G>T; c.109+6T>C; c.86G>A). We conclude that Barth syndrome
      should be included in differential diagnosis of cardiomyopathy in childhood,
      especially in the cooccurrence of dilated cardiomyopathy and 3-methylglutaconic
      aciduria. 

PMID- 24093815
TI  - The relationship between vitamin D deficiency and pulmonary hypertension.
AB  - Vitamin D deficiency actives renin-angiotensin-aldosterone system (RAAS) which
      affects cardiovascular system. Activation of RAAS is associated with pulmonary
      hypertension (PHT). Relation between vitamin D deficiency and PHT could be
      therefore suggested. In our study we compared pulmonary artery pressure between
      vitamin D deficiency and control groups. 115 consecutive patients (average age:
      61.86 +/- 5.86) who have detected very low vitamin D (vitamin D levels < 10
      ng/ml) were enrolled. 117 age matched persons (average age: 61.74 +/- 5.99) were
      selected as the control group. All groups underwent transthoracic
      echocardiography. Routine biochemical measurement of 25-OH vitamin D and
      parathormon (PTH) levels were performed. Baseline characteristics of the study
      groups were comparable. Systolic pulmonary artery pressure (SPAP) of patients in
      the low vitamin D group was higher than the control groups. As a result our
      study, a relation between vitamin D deficiency and pulmonary artery hypertension
      was revealed. 

PMID- 24093816
TI  - 25-hydroxyvitamin D3 concentration in serum and cerebrospinal fluid of patients
      with remitting-relapse multiple sclerosis.
AB  - There is epidemiological, geographical and immunological evidence suggesting that
      low environmental supplies of vitamin D3 may act as a risk factor for developing
      multiple sclerosis (MS), possibly due to dysfunction in the immunomodulatory
      properties of 25-hydroxyvitamin D3 (25-OH-D3) in the brain. The objective of this
      study is to measure the serum and cerebrospinal fluid (CSF) concentrations of 25
      OH-D3 in MS patients during their relapsing phase. 52 patients with remitting
      relapse and 58 patients with other non-inflammatory diseases of central and
      peripheral nervous system were entered into the study. Patients in both groups
      were admitted for the first time to do diagnostic procedures and they were not on
      any other treatment for neurological disorders. The means and medians for serum
      levels of 25-OH-D3 in MS patients and control group were 10.64 +/- 9.2 ng/ml
      (median: 9.6 ng/ml) and 13.23 +/- 17.56 ng/ml (median: 11.90 ng/ml), respectively
      (p=0.328). CSF concentrations for the same values were 2.02 +/- 1.94 ng/ml
      (median: 0.23 ng/ml) and 3.28 +/- 2.96 (median: 0.29 ng/ml), respectively
      (p=0.242). The differences between calculated numbers of serum/CSF ratios were
      not statistically significant too. The serum and CSF concentrations of 25-OH-D3
      in MS group were lower than the control counterpart without any statistical
      difference and the authors did not find any influence of serum 25-OH-D3
      concentration on the CSF concentration based on the non-significant statistical
      difference between the serum/CSF ratios in two study groups of MS patients and
      control cases. 

PMID- 24093817
TI  - Aortic valve leaflet perforation after mitral valve repair.
AB  - A 32-year-old patient with symptomatic severe aortic regurge, 6 weeks after
      mitral valve repair, was admitted for aortic valve surgery. No preoperative
      clinical data consistent with infective endocarditis could be detected.
      Preoperative transthoracic echocardiography showed aortic leaflet perforation
      affecting non coronary cusp. During operation, leaflet perforation was detected
      and closed completely with autologous pericardial patch. No vegetations or
      abscess could be seen during operation. Iatrogenic aetiology of leaflet
      perforation after mitral repair was suspected in this case. Recognition of this
      complication will help in avoiding it during mitral valve surgery and expecting
      it as a possible complication during intraoperative transesophageal
      echocardiography. 

PMID- 24093818
TI  - Association of Mycoplasma pneumoniae infection with Henoch-Schonlein purpura.
AB  - We present a child with Henoch-Schonlein purpura and Mycoplasma pneumoniae
      infection, an association that was rarely described in the literature. The
      infection was confirmed serologically and by using PCR. 

PMID- 24093819
TI  - Painful vaso-occlusive crisis as a prodromal phase of acute chest syndrome. Is
      only one chest X-ray enough? A case report.
AB  - The predominant pathophysiological feature of homozygous sickle cell anemia (SCA)
      is the vaso-occlusion. Vaso-occlusion can be associated with painful crises,
      which are the primary reason for those patients to seek medical care. Vaso
      occlusion is responsible for the acute chest syndrome (ACS) with large morbidity
      and mortality or more rarely (and especially in adults) for priapism and acute
      neurological events (strokes). A 10-year-old boy with homozygous SCA was admitted
      to the Pediatric Emergencies with painful vaso-occlusive crisis and fever.
      Initially he had normal chest X-ray but, after 24-hour-hospitalization, he
      developed ACS with new chest X-ray findings. He was treated with broad spectrum
      antibiotics, blood transfusions and bronchodilators and after a six-day
      treatment, he was significantly improved. The patient was discharged 13 days
      later with no other therapy at home. The possibility of ACS development should be
      still considered, even when a known patient with SCA presents a painful vaso
      occlusive crisis with an initial normal chest X-ray. Therefore, repeated clinical
      examination is required and possible changes in the clinical status could
      indicate the necessity of a new radiographic examination. In this way, early ACS
      could be recognized and the catastrophic consequences due to this syndrome could
      be avoided. 

PMID- 24093820
TI  - Fournier's gangrene in a patient with obesity and B-lymphoma.
AB  - We present a case of Fournier's gangrene disease in a young obese patient with
      coexistent B-lymphoma. It remains controversial if obesity constitutes a
      predisposing factor for an individual to develop necrotizing fasciitis. On the
      other hand, only few cases of patients with coexistence of B-lymphoma and
      Fournier's gangrene disease have been reported. A 30-years-old obese man was
      admitted to emergency department with fever (38.7  degrees C), pain, erythema and
      swelling extended from the left scrotum to the left lower abdominal quadrant. He
      was confused, with low urinary excretion and septic shock's signs. The clinical
      findings were characteristics of Fournier's gangrene disease. Furthermore during
      physical examination a massive, painless and motionless mass in the left breast
      was revealed. The patient required urgent surgical debridement of the affected
      area and pus drainage. Biopsies of the breast mass were received by excision. Pus
      and blood cultures yielded Staphylococci coagulase(-), Klebsiella and Proteus sp.
      Intravenous antibiotic treatment with Meropeneme and Clindamycine started
      immediately. Repeated debridement was often performed. Pathology examination of
      the massive tissue revealed a diffuse B-lymphoma of large cells (Germinal center
      B-cell like- GCB). The patient was discharged from the hospital 35 days later.
      Afterwards, he was treated with chemotherapeutic agents for malignant lymphoma at
      the oncological department. The aim of this case's presentation is to mention
      that young obese patients with Fournier's gangrene disease should be particularly
      investigated due to the possible occurrence of another not obvious predisposing
      factor, such as a malignant disease. 

PMID- 24093821
TI  - Unusual clinical tumor development in axilla.
AB  - This work describes clinical development of a sarcoma in the left axilla of a 36
      year-old woman. The macroscopic picture changed from the initial inflammatory
      reddening to globular resistance of 2.5 cm, suggestive of an enlarged lymph node.
      Mammography did not reveal any associated breast disease. Colliquation found on
      the ultrasound images led to a biopsy, the result of which indicated only an
      inflammation, without any malignancy. Rapid growth of the axillar tumor to 10 cm
      in size within 8 weeks prompted surgery allowing proper diagnosis of a small
      mature-to-immature sarcoma. Special examinations performed by a histopathologist
      (at the Institute for Histopathology) could not establish the precise
      histogenesis, i.e. the tissue origin. Therefore it was necessary to remove any
      clinically obscuring tumor for the final proper histological diagnosis and
      adequate treatment of the patient. 

PMID- 24093822
TI  - The association between the apolipoprotein A1/ high density lipoprotein 
      cholesterol and diabetes in Taiwan - a cross-sectional study.
AB  - BACKGROUND: Traditional lipid indices have been associated with type 2 diabetes,
      but it remains uncertain which lipid index is the best discriminator for
      diabetes. In this study, we aimed to assess lipoproteins, traditional lipid
      variables, and other variables to discover their association with diabetes in the
      Taiwanese population. METHODS: Data from a nationwide cross-sectional population
      based survey of 3087 men and 3373 women in 2002 were analyzed in this study. All
      participants were assessed for anthropometry, glycosylated hemoglobin, fasting
      sugar and lipid profiles with triglycerides, high density lipoprotein-cholesterol
      (HDL-C), low density lipoprotein-cholesterol (LDL-C), and apolipoprotein A1
      (ApoA1) and B (ApoB). The ratio of LDL-C/HDL-C, ApoB/ApoA1, ApoB/LDL-C and
      ApoA1/HDL-C and other variables were analyzed to determine their potential roles
      in type 2 diabetes in the Taiwanese population. The Odds ratios (ORs) of the risk
      variables for diabetes were estimated using logistic regression and were adjusted
      for confounding factors. RESULTS: The increased ratio of ApoA1/HDL-C was
      significantly associated with diabetes in men (top tertile vs. lowest: OR 2.98;
      95% CI: 1.12 - 7.92; P-trend = 0.030) and women (top tertile vs. lowest: OR 2.15;
      95% CI: 1.00 - 4.59; P-trend = 0.047). A modest increased diabetic risk was
      evident with ApoB/LDL-C in women (top tertile vs. lowest: OR 2.03; 95% CI: 1.07-
      3.85; P-trend = 0.028), but not in men (top tertile v. lowest: OR 1.69; 95% CI:
      0.79- 3.62; P-trend = 0.198). CONCLUSIONS: ApoA1/HDL-C had a significant linear
      association with diabetes in both sexes and was superior to other lipid and
      lipoprotein variables among the general Taiwanese population.

PMID- 24093823
TI  - Experimental evidence for asymmetric mate preference and aggression: behavioral
      interactions in a woodrat (Neotoma) hybrid zone.
AB  - BACKGROUND: Female mate preferences may be under strong selection in zones of
      contact between closely related species because of greater variation in available
      mates and the potential costs of hybridization. We studied female mate
      preferences experimentally in a zone of secondary contact between Desert and
      Bryant's Woodrat (Neotoma lepida and N. bryanti) in the southern foothills of the
      Sierra Nevada of California. We tested female preference for conspecific versus
      heterospecific males in paired choice trials in which females could interact
      freely with males, but males could not interact directly with each other. We
      compared preferences of females from both allopatric and sympatric sites.
      RESULTS: We did not find evidence of the process of reinforcement as assortative
      preferences were not stronger in sympatry than in allopatry. Mate preferences,
      however, were asymmetric, with N. lepida females mating preferentially with
      conspecifics and N. bryanti females showing no preference by species. Sympatric
      females were less likely to mate than allopatric females, due in part to an
      increase in aggressive interactions. However, even in the absence of aggression,
      courtship led to mating less often in sympatric females, suggesting they were
      choosier or had lower sexual motivation than allopatric females. CONCLUSIONS:
      Patterns of mate choice in this woodrat system appear to be strongly impacted by
      body size and aggressive behavior. In particular, females of the smaller-bodied
      species rarely interact with the relatively large heterospecific males. In
      contrast females of the larger-bodied species accept the relatively small
      heterospecific males. For sympatric animals, rates of aggression were markedly
      higher than for allopatric animals and reduced affiliative and reproductive
      behavior in our trials. Sympatric animals are larger and more aggressive, traits
      that are likely under strong ecological selection across the sharp resource
      gradient that characterizes the contact zone. However, our results suggest that
      these traits that are likely favored in competitive interactions between the
      species also impact reproductive interactions. Combined with our previous
      findings of post-zygotic isolation in this system, this study suggests that
      multiple isolating mechanisms contribute to the rate of genetic exchange between
      these species when they come into contact, and that these mechanisms are the
      result of selection on traits that are important in a range of ecological and
      reproductive interactions.

PMID- 24093825
TI  - Investigation into physical-chemical variables affecting the manufacture and
      dissolution of wet-milled clarithromycin nanoparticles.
AB  - A critical problem associated with poor water-soluble drugs is their low and
      variable bioavailability, which is derived from the slow dissolution and erratic
      absorption. Nano-formulation has been identified as one approach to enhance the
      rate and extent of drug absorption for compounds that demonstrate limited water
      solubility. This study aimed to investigate the physico-chemical variables that
      affect the manufacture, dissolution and consequent bioavailability of wet-milled
      clarithromycin (CLA) nanoparticles, a macrolide antibiotic. CLA nanoparticles
      were prepared using wet milling method followed by freeze-drying. Different
      stabilizer systems, consisting of surfactants and polymers alone or their
      combinations were studied to determine the optimum conditions for producing nano
      sized CLA particles. In vitro characterizations of the CLA nanoparticles were
      performed using dynamic light scattering, X-ray powder diffraction, differential
      scanning calorimetry and dissolution efficiency test. Results showed that in
      general the wet milling process did not modify the crystallinity of the CLA
      nanoparticles. The poloxamers and polyvinyl alcohol (PVA) stabilizers resulted in
      nanoparticles with the smallest particle size and best dissolution rates.
      Furthermore, poloxamers F68 and F127, and PVA stabilizers demonstrated the best
      performance in increasing dissolution efficacy.

PMID- 24093824
TI  - Does dietary calcium interact with dietary fiber against colorectal cancer? A
      case-control study in Central Europe.
AB  - BACKGROUND: An unfavorable trend of increasing rates of colorectal cancer has
      been observed across modern societies. In general, dietary factors are understood
      to be responsible for up to 70% of the disease's incidence, though there are
      still many inconsistencies regarding the impact of specific dietary items. Among
      the dietary minerals, calcium intake may play a crucial role in the prevention.
      The purpose of this study was to assess the effect of intake of higher levels of
      dietary calcium on the risk of developing of colorectal cancer, and to evaluate
      dose dependent effect and to investigate possible effect modification. METHODS: A
      hospital based case-control study of 1556 patients (703 histologically confirmed
      colon and rectal incident cases and 853 hospital-based controls) was performed
      between 2000-2012 in Krakow, Poland. The 148-item semi-quantitative Food
      Frequency Questionnaire to assess dietary habits and level of nutrients intake
      was used. Data regarding possible covariates was also collected. RESULTS: After
      adjustment for age, gender, education, consumption of fruits, raw and cooked
      vegetables, fish, and alcohol, as well as for intake of fiber, vitamin C, dietary
      iron, lifetime recreational physical activity, BMI, smoking status, and taking
      mineral supplements, an increase in the consumption of calcium was associated
      with the decrease of colon cancer risk (OR = 0.93, 95% CI: 0.89-0.98 for every
      100 mg Ca/day increase). Subjects consumed >1000 mg/day showed 46% decrease of
      colon cancer risk (OR = 0.54, 95% CI: 0.35-0.83). The effect of dietary calcium
      was modified by dietary fiber (p for interaction =0.015). Finally, consistent
      decrease of colon cancer risk was observed across increasing levels of dietary
      calcium and fiber intake. These relationships were not proved for rectal cancer.
      CONCLUSIONS: The study confirmed the effect of high doses of dietary calcium
      against the risk of colon cancer development. This relationship was observed
      across different levels of dietary fiber, and the beneficial effect of dietary
      calcium depended on the level of dietary fiber suggesting modification effect of
      calcium and fiber. Further efforts are needed to confirm this association, and
      also across higher levels of dietary fiber intake.

PMID- 24093828
TI  - Acceptability and feasibility of CyberSenga: an Internet-based HIV-prevention
      program for adolescents in Mbarara, Uganda.
AB  - Capitalizing on emerging data suggesting that HIV-preventive behaviors can be
      positively affected by Internet-based programs, we developed and tested
      CyberSenga, an Internet-based, comprehensive sexuality education program for
      adolescents in Mbarara, Uganda. Three hundred and sixty-six secondary school
      students were randomly assigned to either the five-lesson program (+ booster) or
      a treatment-as-usual control. At three-month follow-up, intervention participants
      provided feedback on the program acceptability. Six focus groups with
      intervention participants were additionally conducted after the final follow-up
      at 6 months. Data support a hypothesis of feasibility: despite schedule
      interruptions, 95% of intervention participants completed all the five modules;
      only 17% deviated from the once-a-week intended delivery schedule. Internet
      service was uninterrupted during the field period and, in general, the technology
      performed to specifications. The intervention also appears to be acceptable: 94%
      of intervention youth somewhat or strongly agreed that they learned a lot and 93%
      said they were somewhat or very likely to recommend the program. Although more
      than two in three youth somewhat or strongly agreed that the program talked too
      much about sex (70%) and condoms (75%), 89% somewhat or strongly disagreed that
      "I do not think kids like me should do the CyberSenga program." Feedback from
      focus group participants further suggested that the content was generally
      acceptable and did not contradict local norms in most cases. In fact, despite
      concerns from some local stakeholders to the contrary, information about condoms
      did not appear to be confusing or contradictory for youth who were abstinent.
      Nonetheless, some of the sexual topics seemed to be unfamiliar or uncomfortable
      for some participants - particularly brief references to oral and anal sex.
      Together, both qualitative and quantitative data suggest that the program is a
      feasible and acceptable way of delivering HIV preventive information to both
      sexually experienced and inexperienced adolescents in Mbarara, Uganda. 

PMID- 24093829
TI  - Bubbles and drops on curved surfaces.
AB  - Surface curvature affects the shape, stability, and apparent contact angle of
      sessile and pendant drops. Here, we develop an approximate analytical solution
      for non-axisymmetric perturbations to small spherical drops on a flat substrate,
      assuming a fixed contact angle and fixed drop volume. The analytical model is
      validated using numerical solutions of the Laplace equation from the Surface
      Evolver software. We investigate the effects of surface curvature on drop shape,
      pressure, and surface energy, ascertaining the energy-gradient force that drives
      lateral drop migration. By balancing this force with the viscous resistance/drag
      force, in the lubrication approximation, we predict velocities of the order of
      0.1 mm s(-1) for 1 mm diameter drops of water with a 30 degrees  contact angle on
      a substrate with a curvature gradient of 0.01 mm(-2), achieved, for example, on a
      harmonic surface with a wavelength of 4 cm and an amplitude of 4 mm. 

PMID- 24093830
TI  - Thioether-promoted direct olefination of polyfluoroarenes catalyzed by palladium.
AB  - A methyl(phenyl)sulfane-promoted direct olefination of polyfluoroarenes catalyzed
      by palladium has been reported. With use of this new thioether ligand, a high
      reaction efficiency and excellent E/Z ratio of desired olefinated
      polyfluoroarenes were obtained. This represents a first example of thioether
      promoted oxidative Heck reaction. 

PMID- 24093831
TI  - Surgical correction of aberrant conjunctival overgrowth in a rabbit: a case
      report.
AB  - A dwarf rabbit presented with unilateral aberrant conjunctival growth.
      Allgoewer's U-suture therapy was initially used to correct the overgrowth.
      Centrifugal incisions extending up to the limbus were made on the hypertrophic
      conjunctiva. Transpalpebral limbal fixation was performed next. When the symptoms
      recurred 3 weeks later, a second operation was performed using the Lembert suture
      method instead. The overgrowing membrane was excised radically just posterior to
      the limbus. The conjunctiva was then sutured using the Lembert pattern. The
      rabbit recovered with no further complications. 

PMID- 24093832
TI  - Establishment of the mild, moderate and severe dry eye models using three methods
      in rabbits.
AB  - BACKGROUND: Dry eye (DE) is a common eye disease, and appropriate animal models
      are essential to explore the pathogenesis and therapy of DE. In this study, we
      aimed to establish rabbit models by three methods. METHODS: In group A, the
      lacrimal gland, Harderian gland, and nictitating membrane of the left eyes were
      surgically removed. In group B, the bulbar conjunctiva of the left eyes was
      burned with 50% trichloroacetic acid. In group C, both methods above were used.
      The right eyes served as normal controls. The Schirmer I test (SIt), fluorescein
      staining, and impression cytology were evaluated at baseline and on days 28, 42,
      and 56. RESULTS: Both the SIt and goblet cell density were significantly lower in
      operated eyes compared to the control eyes, while the corneal fluorescein
      staining scores in the operated eyes were significantly higher than in the
      control eyes on days 28, 42, and 56 (p < 0.05, p < 0.01 or p < 0.001). The SIt
      and goblet cell densities in groups B and C were significantly lower than group A
      on days 28, 42, and 56 (p < 0.05, p < 0.01 or p < 0.001). In addition, the
      corneal fluorescein staining scores in group C were significantly higher than
      either group A or group B on days 28, 42, and 56, while fluorescein staining
      scores were higher in group B than group A on days 42 and 56 days (p < 0.05, p <
      0.01 or p < 0.001), with mean score 3.8 +/- 1.30 (group A), 7.4 +/- 1.14 (group
      B) and 10.8 +/- 1.30 (group C) on day 56. CONCLUSIONS: Results suggest that three
      separate DE models, with mild, moderate, and severe manifestations of DE, could
      be stably established, in which conjunctival goblet cells took an important role.

PMID- 24093834
TI  - Notch signaling in peripheral T-cell lymphoma: revelations from
      immunohistochemistry.

PMID- 24093833
TI  - Exposure to cues associated with palatable food reward results in a dopamine D2
      receptor-dependent suppression of evoked synaptic responses in the entorhinal
      cortex.
AB  - BACKGROUND: The lateral entorhinal cortex receives inputs from ventral tegmental
      area dopamine neurons that are activated by exposure to food-related cues, and
      exogenously applied dopamine is known to modulate excitatory synaptic responses
      within the entorhinal cortex. METHODS: The present study used in vivo synaptic
      field potential recording techniques to determine how exposure to cues associated
      with food reward modulates synaptic responses in the entorhinal cortex of the
      awake rat. Chronically implanted electrodes were used to monitor synaptic
      potentials in the entorhinal cortex evoked by stimulation of the piriform
      (olfactory) cortex, and to determine how synaptic responses are modulated by food
      related cues. RESULTS: The amplitudes of evoked synaptic responses were reduced
      during exposure to cues associated with delivery of chocolate, and during
      delivery of chocolate for consumption at unpredictable intervals. Reductions in
      synaptic responses were not well predicted by changes in behavioural mobility,
      and were not fully blocked by systemic injection of either the D1-like receptor
      antagonist SCH23390, or the muscarinic receptor antagonist scopolamine. However,
      the reduction in synaptic responses was blocked by injection of the D2-like
      receptor antagonist eticlopride. CONCLUSIONS: Exposure to cues associated with
      palatable food results in a suppression of synaptic responses in olfactory inputs
      to the entorhinal cortex that is mediated in part by activation of dopamine D2
      receptors.

PMID- 24093835
TI  - Reporting interim positron emission tomography in diffuse large B-cell lymphoma:
      the Zeno's paradox.

PMID- 24093836
TI  - Novel diagnostic and prognostic biomarkers in esophageal cancer.
AB  - INTRODUCTION: This article provides an overview of actual biomarkers with an
      impact on improvement of diagnosis and treatment of esophageal cancer patients.
      AREAS COVERED: Recent literature has been analyzed and provides information
      regarding the potential role of molecular markers as a diagnostic or prognostic
      factor in esophageal cancer. EXPERT OPINION: Until now, the role of molecular
      markers is far from being firmly established for routine use and is not without
      obstacles. However, with reliable standardized methods, established cut-off
      values and promising candidates in marker panels with markers of genetic,
      epigenetic and proteomic origin might result in a marker tool worthwhile of being
      validated in large, prospective, randomized trials. Novel validated marker
      combinations have to be clinically applied to prove their putative role in
      complementing clinical techniques within the development of better detection
      concepts of esophageal cancer, improving patients' long-term prognosis by early
      and purposive therapy within individualized treatment concepts.

PMID- 24093837
TI  - Measuring heart failure care by 30-day readmission: Rethinking the quality of
      outcome measures.

PMID- 24093838
TI  - The great taboo of non-infarct-related artery revascularization during primary
      percutaneous coronary intervention.

PMID- 24093839
TI  - Measurement of natriuretic peptides at the point of care in the emergency and
      ambulatory setting: current status and future perspectives.
AB  - The measurement of natriuretic peptides (NPs), B-type NP or N-terminal pro-B-type
      NP, can be an important tool in the diagnosis of acute heart failure in patients
      presenting to an Emergency Department (ED) with acute dyspnea, according to
      international guidelines. Studies and subsequent meta-analyses are mixed on the
      absolute value of routine NP assessment of ED patients. However, levels of NPs
      are likely to be used also to guide treatment and to assess risk of adverse
      outcomes in other patients at risk of developing heart failure, including those
      with pulmonary embolism or diabetes, or receiving chemotherapy. Natriuretic
      peptide levels, like other biomarkers, can now be measured at the point of care
      (POC). We have reviewed the current status of NP measurement together with the
      potential contribution of POC measurement of NPs to clinical care delivery in the
      emergency and other settings. Several POC systems for measuring NP levels are now
      available: these produce test results within 15 minutes and appear sufficiently
      sensitive and robust to be used routinely in diagnostic evaluations. Point-of
      care systems could be used to assess NP levels in the ED and community outpatient
      settings to monitor the risk of acute heart failure. Furthermore, the use of
      protocol-driven POC testing of NP within the time frame of a patient consultation
      in the ED may facilitate and accelerate the throughput and disposition of at-risk
      patients. Appropriately designed clinical trials will be needed to confirm these
      potential benefits. It is also important that processes of care delivery are
      redesigned to take full advantage of the faster turnaround times provided by POC
      technology. 

PMID- 24093841
TI  - Learning from recent trials and shaping the future of acute heart failure trials.
AB  - The last decade of acute heart failure (HF) research is characterized by
      disappointments in large phase 2 and 3 pharmacologic studies of therapeutics
      including calcium-sensitizing agents and antagonists of endothelin, vasopressin,
      and adenosine. As a result, pharmacologic management for acute HF has changed
      little in recent years, and adverse event rates remain higher than in chronic HF.
      Despite neutral results in many acute HF trials, recent studies including RELAX
      AHF, ASTRONAUT, and PRONTO have highlighted the role of appropriate timing of
      patient enrollment, targeting the "right" patients, and selecting appropriate end
      points and sites. We describe lessons learned from recent trials in acute HF and
      outline strategies to improve the potential for success in future trials. This
      review is based on discussions between scientists, clinical trialists, and
      regulatory representatives at the 9th Global Cardio Vascular Clinical Trialists
      Forum in Paris, France, from November 30 to December 1, 2012. 

PMID- 24093840
TI  - Rheumatoid arthritis and cardiovascular disease.
AB  - BACKGROUND: Rheumatic disease and heart disease share common underpinnings
      involving inflammation. The high levels of inflammation that characterize
      rheumatic diseases provide a "natural experiment" to help elucidate the
      mechanisms by which inflammation accelerates heart disease. Rheumatoid arthritis
      (RA) is the most common of the rheumatic diseases and has the best studied
      relationships with heart disease. METHODS: A review of current literature on
      heart disease and RA was conducted. RESULTS: Patients with RA have an increased
      risk of developing heart disease that is not fully explained by traditional
      cardiovascular risk factors. Therapies used to treat RA may also affect the
      development of heart disease; by suppressing inflammation, they may also reduce
      the risk of heart disease. However, their other effects, as in the case of
      steroids, may increase heart disease risk. CONCLUSIONS: Investigations of the
      innate and adaptive immune responses occurring in RA may delineate novel
      mechanisms in the pathogenesis of heart disease and help identify novel
      therapeutic targets for the prevention and treatment of heart disease.

PMID- 24093843
TI  - Multistate implementation of guideline-based cardiac resuscitation systems of
      care: description of the HeartRescue project.
AB  - BACKGROUND: There is large and significant regional variation in out-of-hospital
      cardiac arrest (OHCA), and despite advances in treatment, survival remains low.
      The American Heart Association has called for the creation of integrated cardiac
      resuscitation systems of care capable of measuring and improving evidence-based
      care from bystanders through to hospital discharge. METHODS: The HeartRescue
      Project was initiated in 2010 by the Medtronic Foundation in collaboration with 5
      academic medical centers and American Medical Response. The HeartRescue Project
      aims to develop regional cardiac resuscitation systems of care that will
      implement guideline-based best practice bystander, prehospital, and hospital care
      with standardized data reporting linked to outcomes. The primary goal is to
      improve collective OHCA survival by 50% over 5 years. RESULTS: The total
      population in the 5 participating states is 41.1 million. At baseline, the
      HeartRescue Project covers approximately 26.1 million people (63.6%) and has
      engaged 767 emergency medical services agencies and 269 hospitals. Data will be
      collected for quality improvement, to inform provider feedback, and serve to
      define effective strategies to improve cardiac arrest care. CONCLUSION: The
      HeartRescue Project is the largest public health initiative of its kind focused
      entirely on cardiac arrest outcomes. The project is designed to significantly
      improve OHCA survival by implementing and measuring model systems of care for
      cardiac resuscitation.

PMID- 24093842
TI  - Prospective Urban Rural Epidemiology (PURE) study: Baseline characteristics of
      the household sample and comparative analyses with national data in 17 countries.
AB  - BACKGROUND: The PURE study was established to investigate associations between
      social, behavioural, genetic, and environmental factors and cardiovascular
      diseases in 17 countries. In this analysis we compare the age, sex, urban/rural,
      mortality, and educational profiles of the PURE participants to national
      statistics. METHODS: PURE employed a community-based sampling and recruitment
      strategy where urban and rural communities were selected within countries. Within
      communities, representative samples of adults aged 35 to 70 years and their
      household members (n = 424,921) were invited for participation. RESULTS: The PURE
      household population compared to national statistics had more women (sex ratio
      95.1 men per 100 women vs 100.3) and was older (33.1 years vs 27.3), although age
      had a positive linear relationship between the two data sources (Pearson's r =
      0.92). PURE was 59.3% urban compared to an average of 63.1% in participating
      countries. The distribution of education was less than 7% different for each
      category, although PURE households typically had higher levels of education. For
      example, 37.8% of PURE household members had completed secondary education
      compared to 31.3% in the national data. Age-adjusted annual mortality rates
      showed positive correlation for men (r = 0.91) and women (r = 0.92) but were
      lower in PURE compared to national statistics (7.9 per 1000 vs 8.7 for men; 6.7
      vs 8.1 for women). CONCLUSIONS: These findings indicate that modest differences
      exist between the PURE household population and national data for the indicators
      studied. These differences, however, are unlikely to have much influence on
      exposure-disease associations derived in PURE. Further, incidence estimates from
      PURE, stratified according to sex and/or urban/rural location will enable valid
      comparisons of the relative rates of various cardiovascular outcomes across
      countries.

PMID- 24093844
TI  - Rationale, design, and baseline characteristics of the Study assessInG the
      morbidity-mortality beNefits of the If inhibitor ivabradine in patients with
      coronarY artery disease (SIGNIFY trial): a randomized, double-blind, placebo
      controlled trial of ivabradine in patients with stable coronary artery disease
      without clinical heart failure.
AB  - BACKGROUND: Elevated heart rate in stable coronary artery disease (CAD) is
      associated with worse outcomes, particularly increased risk of myocardial
      infarction. Heart rate reduction with the If inhibitor ivabradine confers
      symptomatic benefits in angina pectoris and reduces coronary events in patients
      with stable CAD and left ventricular (LV) systolic dysfunction, with a resting
      heart rate of >=70 beats/min. The SIGNIFY trial is testing the hypothesis that
      heart rate reduction using ivabradine reduces mortality and cardiovascular events
      in patients with stable CAD, but without clinical heart failure. METHODS: The
      SIGNIFY trial is a randomized, double-blind, parallel-group, placebo-controlled,
      event-driven study in patients with stable CAD (1,139 centers, 51 countries).
      Participants are 55 years or older, with stable CAD and an LV ejection fraction
      >40%, in sinus rhythm, with a baseline resting heart rate of >=70 beats/min, and
      with at least 1 additional cardiovascular risk factor. At inclusion, patients
      receive ivabradine 7.5 mg twice a day or matching placebo, which is adjusted at
      every visit to a heart rate target of 60 beats/min. Participants should receive
      the best possible background treatment for stable CAD. The primary end point is a
      composite of cardiovascular death or nonfatal myocardial infarction. RESULTS:
      Recruitment lasted from October 2009 to April 2012. The SIGNIFY trial has
      recruited 19,102 patients (age 65.0 +/- 7.2 years, resting heart rate 77.2 +/-
      7.0 beats/min, 72% male) with no evidence for LV dysfunction (ejection fraction
      56.5% +/- 8.6%). CONCLUSION: The SIGNIFY trial will shed further light on the
      role of heart rate lowering with ivabradine in patients with stable CAD without
      clinical heart failure. The study is expected to end in 2014.

PMID- 24093845
TI  - Fractional flow reserve versus angiography in guiding management to optimize
      outcomes in non-ST-elevation myocardial infarction (FAMOUS-NSTEMI): rationale and
      design of a randomized controlled clinical trial.
AB  - BACKGROUND: In patients with acute non-ST-elevation myocardial infarction
      (NSTEMI), coronary arteriography is usually recommended; but visual
      interpretation of the angiogram is subjective. We hypothesized that functional
      assessment of coronary stenosis severity with a pressure-sensitive guide wire
      (fractional flow reserve [FFR]) would have additive diagnostic, clinical, and
      health economic utility as compared with angiography-guided standard care.
      METHODS AND DESIGN: A prospective multicenter parallel-group 1:1 randomized
      controlled superiority trial in 350 NSTEMI patients with >=1 coronary stenosis
      >=30% severity (threshold for FFR measurement) will be conducted. Patients will
      be randomized immediately after coronary angiography to the FFR-guided group or
      angiography-guided group. All patients will then undergo FFR measurement in all
      vessels with a coronary stenosis >=30% severity including culprit and nonculprit
      lesions. Fractional flow reserve will be disclosed to guide treatment in the FFR
      guided group but not disclosed in the "angiography-guided" group. In the FFR
      guided group, an FFR <=0.80 will be an indication for revascularization by
      percutaneous coronary intervention or coronary artery bypass surgery, as
      appropriate. The primary outcome is the between-group difference in the
      proportion of patients allocated to medical management only compared with
      revascularization. Secondary outcomes include the occurrence of cardiac death or
      hospitalization for myocardial infarction or heart failure, quality of life, and
      health care costs. The minimum and average follow-up periods for the primary
      analysis are 6 and 18 months, respectively. CONCLUSIONS: Our developmental
      clinical trial will address the feasibility of FFR measurement in NSTEMI and the
      influence of FFR disclosure on treatment decisions and health and economic
      outcomes.

PMID- 24093846
TI  - Dual antiplatelet therapy versus oral anticoagulation plus dual antiplatelet
      therapy in patients with atrial fibrillation and low-to-moderate thromboembolic
      risk undergoing coronary stenting: design of the MUSICA-2 randomized trial.
AB  - BACKGROUND: Oral anticoagulation (OAC) is the recommended therapy for patients
      with atrial fibrillation (AF) because it reduces the risk of stroke and other
      thromboembolic events. Dual antiplatelet therapy (DAPT) is required after
      percutaneous coronary intervention and stenting (PCI-S). In patients with AF
      requiring PCI-S, the association of DAPT and OAC carries an increased risk of
      bleeding, whereas OAC therapy or DAPT alone may not protect against the risk of
      developing new ischemic or thromboembolic events. OBJECTIVE: The MUSICA-2 study
      will test the hypothesis that DAPT compared with triple therapy (TT) in patients
      with nonvalvular AF at low-to-moderate risk of stroke (CHADS2 score <=2) after
      PCI-S reduces the risk of bleeding and is not inferior to TT for preventing
      thromboembolic complications. DESIGN: The MUSICA-2 is a multicenter, open-label
      randomized trial that will compare TT with DAPT in patients with AF and CHADS2
      score <=2 undergoing PCI-S. The primary end point is the incidence of stroke or
      any systemic embolism or major adverse cardiac events: death, myocardial
      infarction, stent thrombosis, or target vessel revascularization at 1 year of PCI
      S. The secondary end point is the combination of any cardiovascular event with
      major or minor bleeding at 1 year of PCI-S. The calculated sample size is 304
      patients. CONCLUSIONS: The MUSICA-2 will attempt to determine the most effective
      and safe treatment in patients with nonvalvular AF and CHADS2 score <=2 after PCI
      S. Restricting TT for AF patients at high risk for stroke may reduce the
      incidence of bleeding without increasing the risk of thromboembolic
      complications.

PMID- 24093847
TI  - Complementary prognostic utility of myocardial blush grade and ST-segment
      resolution after primary percutaneous coronary intervention: analysis from the
      HORIZONS-AMI trial.
AB  - BACKGROUND: Both ST-segment resolution (STR) and myocardial blush grade (MBG)
      have prognostic utility after primary percutaneous coronary intervention (PCI)
      for ST-elevation myocardial infarction. We sought to clarify how frequently MBG
      and STR provide discordant measures of reperfusion success and to determine the
      independent prognostic significance of each on long-term outcomes. METHODS: In
      HORIZONS-AMI, core laboratory measures of both MBG and STR were assessed in 2,367
      patients undergoing primary PCI. Four groups were identified based on MBG (grades
      2/3 vs 0/1) and STR (>=50% vs <50%). A multivariable model identified predictors
      of death and major adverse cardiac events at 3 years. RESULTS: Myocardial blush
      grade 2/3 was achieved in 77.7% of patients, and STR >=50% was achieved in 75.1%
      of patients. Myocardial blush grade and STR were discordant in 765 patients
      (30.9%). By multivariable analysis, MBG 2/3 compared with 0/1 was an independent
      predictor of lower mortality at 3 years (4.4% vs 8.4%, adjusted hazard ratio [HR]
      = 0.57 [0.39, 0.82], P = .003). In contrast, STR >=50% compared with <50% was not
      associated with mortality (5.1% vs 5.9%, adjusted HR = 1.11 [0.68, 1.56], P =
      .89). However, repeated revascularization at 3 years was less frequent when STR
      >=50% (12.4% vs 17.6%, adjusted HR = 0.74 [0.58, 0.95], P = .02). In contrast,
      MBG 2/3 vs 0/1 was not associated with reduced repeated revascularization (13.6%
      vs 14.1%, adjusted HR = 1.02 [0.79, 1.33], P = .85). CONCLUSIONS: In HORIZONS
      AMI, MBG and STR after primary PCI were concordant in only 70% of patients and
      provided complementary prognostic information. Myocardial blush grade predicted
      long-term survival, whereas STR predicted freedom from repeated
      revascularization.

PMID- 24093848
TI  - Non-infarct-related artery revascularization during primary percutaneous coronary
      intervention for ST-segment elevation myocardial infarction: a systematic review
      and meta-analysis.
AB  - BACKGROUND: In patients with ST-elevation myocardial infarction (STEMI) and
      multivessel disease, guidelines recommend infarct-related artery (IRA) only
      intervention during primary percutaneous coronary intervention (PCI) except in
      patients with hemodynamic instability. To assess the available evidence, we
      performed a systematic review and meta-analysis comparing outcomes of non-IRA PCI
      as an adjunct to primary PCI (same sitting PCI [SS-PCI]) with IRA only PCI (IRA
      PCI) in the setting of STEMI. METHODS AND RESULTS: A comprehensive search
      identified 14 studies [11 cohort, 3 randomized controlled trials] comprising of
      35,239 patients. For cohort studies, patients undergoing SS-PCI had higher rate
      of anterior infarction (48% vs. 45%, P = .04) and cardiogenic shock (11% vs. 9%,
      P = .0001) at baseline compared with IRA-PCI. The primary composite end point of
      death, myocardial infarction and revascularization was higher in the SS-PCI group
      in the short term (OR, 1.63; CI, 1.12-2.37) and long term (OR, 1.60; CI, 1.18
      2.16). However, after excluding patients with shock, there was no difference in
      primary endpoint for the short (OR, 1.33; CI, 0.67-2.63) and long term (OR, 1.39;
      CI, 0.80-2.42) follow-up. In analyses limited to randomized controlled trials,
      primary end point was similar during short term (OR, 0.79; CI, 0.19-3.28) and
      significantly lower for SS-PCI group in the long term (OR, 0.55; CI, 0.34-0.91).
      CONCLUSIONS: There is paucity of randomized data to guide management of STEMI
      patients with multivessel disease. SS-PCI group in cohort studies has higher
      baseline risk compared to IRA-PCI. The primary end point is higher for SS-PCI in
      observational cohort studies but this difference did not persist after exclusion
      of shock patients and for analysis limited to randomized controlled trials. These
      findings underscore the need of a large randomized controlled trial to guide
      therapy for a commonly encountered clinical situation.

PMID- 24093849
TI  - Predictors of normal coronary arteries at coronary angiography.
AB  - BACKGROUND: Coronary angiograms are important in the diagnostic workup of
      patients with suspected coronary artery disease. However, little is known about
      the clinical predictors of normal angiograms and whether this rate varies across
      different cardiac centers in Ontario. METHODS: We conducted a study using the
      Cardiac Care Network Variations in Revascularization Practice in Ontario database
      of 2,718 patients undergoing an index cardiac catheterization for an indication
      of stable angina between April 2006 and March 2007 at one of 17 cardiac hospitals
      in Ontario. We determined predictors of normal coronary angiograms (0% coronary
      stenosis) and compared rates of patients with normal catheterizations across
      centers. RESULTS: Overall, 41.9% of patients with stable angina had a normal
      catheterization. A multivariate model demonstrated female gender to be the
      strongest predictor of a normal angiogram (odds ratio 3.55, 95% CI 2.93-4.28). In
      addition, atypical ischemic symptoms or no symptoms, the absence of diabetes,
      hyperlipidemia, smoking history, peripheral vascular disease, and angiography
      performed at a nonteaching site were associated with higher rates of normal
      catheterization. The rate of normal angiograms studied varied from 18.4% to 76.9%
      across hospitals and was more common in community compared with academic settings
      (47.1% vs 35.4%, P < .001). CONCLUSIONS: The absence of traditional cardiac risk
      factors, female gender, and lack of typical angina symptoms are all associated
      with a higher frequency of normal cardiac catheterizations. The wide variation in
      Ontario in the frequency of normal angiograms in patients with stable angina
      suggests that there are opportunities to improve patient case selection.

PMID- 24093850
TI  - The feasibility and accuracy of evaluating lipid management performance metrics
      using an electronic health record.
AB  - BACKGROUND: Over the past decade, electronic health records (EHRs) have emerged
      as a potential tool to assess quality of care; however, the feasibility and
      accuracy of EHRs to assess adherence to lipid management performance measures
      have not been evaluated. METHODS: We created a retrospective cohort of 3779
      patients with coronary artery disease who were followed up in a cardiology clinic
      at an academic medical center using an EHR database. Of these 3779 patients, 300
      randomly-selected charts were reviewed to identify reasons for failure to adhere
      to lipid management performance measures. RESULTS: Based on the EHR, a low
      density lipoprotein cholesterol measurement was obtained in 73% of patients
      within the past 3 years; of which, 34% had low-density lipoprotein cholesterol
      levels >=100 mg/dL and statin therapy had been prescribed in 88%. Manual chart
      review revealed that many of these apparent failures were actually false
      positives, due to inaccurate capture of indications and contraindications to
      lipid measurement and statin prescription, patient/provider treatment
      preferences, and external data sources. CONCLUSIONS: While it is possible to
      monitor adherence to lipid management performance measures using an EHR, the
      accuracy of this assessment is currently limited and may underestimate provider
      quality of care.

PMID- 24093851
TI  - Use of aldosterone antagonists at discharge after myocardial infarction: results
      from the National Cardiovascular Data Registry Acute Coronary Treatment and
      Intervention Outcomes Network (ACTION) Registry-Get with the Guidelines (GWTG).
AB  - BACKGROUND: Aldosterone antagonists (AldA) improve survival after myocardial
      infarction (MI) in patients with left ventricular systolic dysfunction (ejection
      fraction [EF] <40%) concomitant with either clinical heart failure (HF) or
      diabetes mellitus (DM). Although current American College of Cardiology/American
      Heart Association guidelines provide a class I recommendation for AldA therapy in
      such patients, how US practice reflects these recommendations is unclear.
      METHODS: Using data from the National Cardiovascular Data Registry ACTION
      Registry-GWTG, we describe contemporary discharge AldA prescription patterns
      among 202,213 patients discharged after acute MI from 526 US sites participating
      in ACTION Registry-GWTG between January 2007 and March 2011. RESULTS: Overall,
      10.0% of patients were eligible for AldA without documented contraindication,
      with only 14.5% of eligible patients receiving AldA at discharge. Among the
      subset of AldA-eligible patients discharged on otherwise optimal medical therapy
      (68.9%), AldAs were prescribed to 16.1%. Aldosterone antagonist use was higher in
      patients with EF <40% and clinical HF with or without DM (17.7% and 16.6%,
      respectively), compared with patients with EF <40% and DM without clinical HF
      (7.8%, P < .001 for each). Fewer than 2% of participating centers used AldA in
      >=50% of eligible patients. CONCLUSIONS: Despite clinical outcome evidence and
      class I guideline recommendations, AldAs are underused in the United States, with
      only 1 in 7 eligible patients prescribed AldA at discharge after MI. This
      contrasts with high use of other evidence-based post-MI medications and
      identifies a specific gap in translation of evidence into clinical practice.

PMID- 24093852
TI  - Prognostic significance of presenting blood pressure in non-ST-segment elevation
      acute coronary syndrome in relation to prior history of hypertension.
AB  - BACKGROUND: Hypertension is a well-established risk factor for cardiovascular
      disease, whereas low systolic blood pressure (SBP) is a powerful adverse
      prognosticator in acute coronary syndrome. However, it is unclear whether the
      prognostic significance of low SBP differs in patients with versus without prior
      history of hypertension. We sought to investigate the relationships between
      presenting SBP, prior hypertension, antihypertensive medication use, and outcomes
      in non-ST-segment elevation acute coronary syndrome (NSTEACS). METHODS: Using
      data from GRACE/GRACE(2) and CANRACE, we stratified 10,337 patients with NSTEACS
      from 1999 to 2008 into 2 groups: those with and those without prior diagnosis of
      hypertension. We performed multivariable logistic regression analysis to assess
      the prognostic significance of prior hypertension on in-hospital mortality and
      tested for the interactions between prior hypertension, antihypertensive
      medication use, and presenting SBP. RESULTS: Compared with patients without prior
      hypertension (n = 3,732), those with prior hypertension (n = 6,605) were older;
      more likely to be female; and more frequently had diabetes, previous myocardial
      infarction, heart failure, renal insufficiency, and higher Killip class and GRACE
      risk scores on presentation. Patients with prior hypertension were more likely to
      be on antihypertensive medications before admission, to present with higher SBP,
      and to have heart failure or cardiogenic shock in hospital (6.0% vs 10.1%; P <
      .001). In-hospital mortality was higher among patients presenting with lower SBP
      but did not differ between the groups with and without prior hypertension. In
      multivariable analysis, neither prior hypertension (adjusted odds ratio = 1.15,
      95% CI 0.78-1.70, P = .48) nor the number of antihypertensive medications used (P
      for trend = .84) was independently associated with in-hospital mortality. In
      contrast, SBP was a strong independent predictor of in-hospital mortality
      (adjusted odds ratio = 1.21 per 10 mm Hg lower, 1.15-1.27, P < .001). There was
      no significant interaction between SBP and prior hypertension (P for interaction
      = .62) or pre-admission antihypertensive medication use (P for interaction = .46)
      with respect to in-hospital mortality. CONCLUSION: Low SBP on presentation, but
      not prior hypertension, was independently associated with in-hospital mortality
      in NSTEACS. The powerful prognostic value of SBP is similar regardless of a
      history of hypertension or pre-admission antihypertensive medication use.

PMID- 24093853
TI  - Association between bleeding and mortality among women and men with high-risk
      acute coronary syndromes: insights from the Early versus Delayed, Provisional
      Eptifibatide in Acute Coronary Syndromes (EARLY ACS) trial.
AB  - BACKGROUND: Female sex is an established risk factor for bleeding, which is an
      important safety end point in patients presenting with non-ST-segment elevation
      acute coronary syndromes (NSTE ACS). However, it is unknown whether the
      association between bleeding and mortality is modulated by sex in this patient
      population. METHODS: We examined the interaction between sex and bleeding and 30
      day mortality outcomes among 2,975 women and 6,431 men with high-risk NSTE ACS
      enrolled in the EARLY ACS trial. The Global Utilization of Strategies to Open
      Occluded Arteries (GUSTO) criteria were used to identify moderate or severe
      bleeds. RESULTS: Women were older and had more comorbid disease compared with
      men. Bleeding rates were higher among women (8.2%) than among men (5.5%; P <
      .01). However, the association of bleeding and 30-day mortality was stronger
      among men (odds ratio 5.8, 95% CI 3.9-8.8) than among women (odds ratio 1.5, 95%
      CI 0.8-2.9; sex * bleeding interaction P < .01). Sex differences in the
      association of bleeding and mortality persisted in a landmark analysis of 120
      hour survivors. CONCLUSIONS: In a contemporary high-risk NSTE ACS cohort, women
      had higher bleeding rates than did men. Paradoxically, the association between
      bleeding and mortality was worse among men than among women.

PMID- 24093854
TI  - Effect of marital status on the outcome of patients undergoing elective or urgent
      coronary revascularization.
AB  - BACKGROUND: Marriage confers various health advantages in the general population.
      However, the added value of marriage among patients who undergo percutaneous
      coronary intervention (PCI) beyond the standard cardiovascular risk factors is
      not clear. This study aimed to assess the effects of marital status on outcomes
      of patients undergoing elective or urgent PCI. METHODS: Clinical observational
      analysis of consecutive patients undergoing elective or urgent PCI from 1993 to
      2011 was performed. Patients were stratified by marital status, comparing married
      to unmarried patients. Clinical outcome up to 12 months was obtained by telephone
      contact or office visit. A total of 11,216 patients were included in the present
      analysis; 55% were married and 45% unmarried. RESULTS: Significant differences in
      baseline characteristics were noted, including a lower prevalence of hypertension
      (86% vs 88%), diabetes (34% vs 38%), and smoking (19% vs 25%) among married vs
      unmarried patients, respectively (P < .001). However, married patients had a
      higher prevalence of hypercholesterolemia and family history of coronary artery
      disease. Early and late major adverse cardiac event rates were significantly
      lower for married vs unmarried patients up to 1 year (13.3% vs 8.2%, P < .001).
      Married status was independently associated with improved outcome in
      multivariable analysis (hazard ratio 0.7, 95% CI 0.6-0.9). CONCLUSIONS: Married
      patients who undergo urgent or elective PCI have superior short- and long-term
      outcomes up to 1 year when compared with unmarried patients. These benefits
      persist after adjustment for multiple traditional cardiovascular risk factors.

PMID- 24093855
TI  - Failure to reassess ejection fraction after acute myocardial infarction in
      potential implantable cardioverter/defibrillator candidates: insights from the
      Translational Research Investigating Underlying disparities in acute Myocardial
      infarction Patients' Health Status (TRIUMPH) registry.
AB  - BACKGROUND: Current practice guidelines advocate delaying assessment of primary
      prevention implantable cardioverter/defibrillator (ICD) candidacy at least 40
      days after an acute myocardial infarction (AMI) because early ICD implantation
      after AMI has not demonstrated survival benefit. The rate at which interval
      reassessment of left ventricular ejection fraction (LVEF) occurs in potential
      primary prevention ICD candidates is unknown. METHODS: We examined patients with
      AMI in the TRIUMPH registry with inhospital LVEF <40% discharged alive after
      their index presentation, excluding patients with a prior ICD and those who
      declined ICD during the index admission or were discharged to hospice. We
      conducted multivariable Poisson modeling to identify independent factors
      associated with LVEF reassessment by 6 months after AMI. RESULTS: Of the 533
      patients meeting the inclusion criteria, only 187 (35.1%) reported LVEF
      reassessment in the first 6 months after AMI and only 13 patients (2.4%)
      underwent ICD implantation by 1 year. In multivariable analysis, early cardiology
      follow-up after AMI was associated with a higher likelihood of LVEF reassessment
      (odds ratio 1.16, 95% confidence interval 1.06-1.28), whereas uninsured status
      and cardiologist-driving inpatient medical decision making were associated with a
      lower likelihood of LVEF reassessment (odds ratios 0.84 [95% CI 0.74-0.96] and
      0.78 [95% CI 0.68-0.91], respectively). CONCLUSIONS: In contemporary practice,
      almost 2 of 3 potential primary prevention ICD candidates did not report follow
      up LVEF evaluation, with a very low rate of ICD implantation at 1 year. These
      results suggest an important gap in quality, highlighting the need for better
      transitions of care.

PMID- 24093856
TI  - A combined anatomic and electrophysiologic substrate based approach for sudden
      cardiac death risk stratification.
AB  - BACKGROUND: Although left ventricular ejection fraction (LVEF) is the primary
      determinant for sudden cardiac death (SCD) risk stratification, in isolation,
      LVEF is a sub-optimal risk stratifier. We assessed whether a multi-marker
      strategy would provide more robust SCD risk stratification than LVEF alone.
      METHODS: We collected patient-level data (n = 3355) from 6 studies assessing the
      prognostic utility of microvolt T-wave alternans (MTWA) testing. Two thirds of
      the group was used for derivation (n = 2242) and one-third for validation (n =
      1113). The discriminative capacity of the multivariable model was assessed using
      the area under the receiver-operating characteristic curve (c-index). The primary
      endpoint was SCD at 24 months. RESULTS: In the derivation cohort, 59 patients
      experienced SCD by 24 months. Stepwise selection suggested that a model based on
      3 parameters (LVEF, coronary artery disease and MTWA status) provided optimal SCD
      risk prediction. In the derivation cohort, the c-index of the model was 0.817,
      which was significantly better than LVEF used as a single variable (0.637, P <
      .001). In the validation cohort, 36 patients experienced SCD by 24 months. The c
      index of the model for predicting the primary endpoint was again significantly
      better than LVEF alone (0.774 vs 0.671, P = .020). CONCLUSIONS: A multivariable
      model based on presence of coronary artery disease, LVEF and MTWA status provides
      significantly more robust SCD risk prediction than LVEF as a single risk marker.
      These findings suggest that multi-marker strategies based on different aspects of
      the electro-anatomic substrate may be capable of improving primary prevention
      implantable cardioverter-defibrillator treatment algorithms.

PMID- 24093857
TI  - Atrial fibrillation in myocardial infarction patients: Impact on health care
      utilization.
AB  - BACKGROUND: Atrial fibrillation (AF) often complicates myocardial infarction
      (MI). While AF adversely impacts survival in MI patients, the impact of AF on
      health care utilization has not been studied. METHODS: The risk of
      hospitalizations, emergency department (ED) visits, and outpatient visits
      associated with prior, new-onset (<30 days post-MI), and late-onset (>=30 days
      post-MI) AF was assessed among incident MI patients from the Olmsted County,
      Minnesota, community. RESULTS: Of 1,502 MI patients, 237 had prior AF, 163
      developed new-onset AF, 113 developed late-onset AF, and 989 had no AF. Over a
      mean follow-up of 3.9 years, 3,661 hospitalizations, 5,559 ED visits, and 80,240
      outpatient visits occurred. After adjustment, compared with patients without AF,
      those with prior and new-onset AF exhibited a 1.6-fold and 1.3-fold increased
      risk of hospitalization, respectively. In contrast, late-onset AF carried a 2.2
      fold increased risk of hospitalization. The hazard ratios were 1.4, 1.2, and 1.8
      for ED visits and 1.4, 1.2, and 1.7 for outpatient visits for prior, new-onset,
      and late-onset AF. Additional adjustment for time-dependent recurrent MI and
      heart failure attenuated the results slightly for hospitalizations and ED visits;
      however, patients with late-onset AF still exhibited a >50% increased risk for
      both utilization measures. CONCLUSIONS: In MI patients, the risk of
      hospitalizations, ED visits, and outpatient visits differed by the timing of AF
      onset, with the greatest risk conferred by late-onset AF. Atrial fibrillation
      imparts an adverse prognosis after MI, underscoring the importance of its
      management in MI patients.

PMID- 24093858
TI  - Functional electrical stimulation of peripheral muscles improves endothelial
      function and clinical and emotional status in heart failure patients with
      preserved left ventricular ejection fraction.
AB  - BACKGROUND: Functional electrical stimulation (FES) improves exercise capacity,
      quality of life, emotional stress, and endothelial function in chronic heart
      failure with impaired systolic function. We sought to investigate the effects of
      FES on the above parameters in patients with preserved ejection fraction (HFpEF).
      METHODS: Thirty HFpEF patients, 18 female and 12 male, aged 69 +/- 8 years, in
      New York Heart Association class II or III and with mean ejection fraction 63% +/
      6%, were randomly (1:1) assigned to a 6-week FES program or placebo. Assessment
      was performed at baseline and after completion of training protocol and included
      6-minute walked distance, quality of life (Kansas City Cardiomyopathy
      Questionnaire and Minnesota Living with Heart Failure Questionnaire), depressive
      symptoms (Beck Depression Inventory and Zung self-rated depression scores), B
      type natriuretic peptide, endothelial function (flow-mediated dilatation), and
      left ventricular diastolic function. RESULTS: A significant improvement in 6
      minute walked distance (F = 21.61, P = .001), Kansas City Cardiomyopathy
      Questionnaire summary (F = 8.68, P = .006), Minnesota Living with Heart Failure
      Questionnaire (F = 6.43, P = .017), Beck Depression Inventory (F = 6.66, P =
      .015), Zung (F = 6.25, P = .019), and flow-mediated dilatation diameter (F =
      11.98, P = .002) was observed in the FES group compared with placebo group; B
      type natriuretic peptide also declined but not significantly (F = 0.249, P =
      .622), and there was a tendency toward lower mitral E/e' wave ratio (F = 3.066, P
      = .091). CONCLUSION: As in heart failure and reduced left ventricular ejection
      fraction, FES also improves exercise capacity, quality of life, emotional status,
      and endothelial function in HFpEF. Given the lack of effective evidence-based
      therapies in these patients, FES warrants further investigation.

PMID- 24093859
TI  - Measuring frailty in heart failure: a community perspective.
AB  - BACKGROUND: Frailty, an important prognostic indicator in heart failure (HF), may
      be defined as a biological phenotype or an accumulation of deficits. Each method
      has strengths and limitations, but their utility has never been evaluated in the
      same community HF cohort. METHODS: Southeastern Minnesota residents with HF were
      recruited from 2007 to 2011. Frailty according to the biological phenotype was
      defined as 3 or more of: weak grip strength, physical exhaustion, slowness, low
      activity and unintentional weight loss >10 lb in 1 year. Intermediate frailty was
      defined as 1 to 2. The deficit index was defined as the proportion of deficits
      present out of 32 deficits. RESULTS: Among 223 patients (mean age 71 +/- 14, 61%
      male), 21% were frail and 48% intermediate frail according to the biological
      phenotype. The deficit index ranged from 0.02-0.75, with a mean (SD) of 0.25
      (0.13). Over a mean follow-up of 2.4 years, 63 patients died. After adjustment
      for age, sex and ejection fraction, patients categorized as frail by the
      biological phenotype had a 2-fold increased risk of death compared to those with
      no frailty, whereas a 0.1 unit increase in the deficit index was associated with
      a 44% increased risk of death. Both measures predicted death equally (C
      statistics: 0.687 for biological phenotype and 0.700 for deficit index).
      CONCLUSION: The deficit index and the biological phenotype equally predict
      mortality. As the biological phenotype is not routinely assessed clinically, the
      deficit index, which can be ascertained from medical records, is a feasible
      alternative to ascertain frailty.

PMID- 24093860
TI  - Screening of MYH7, MYBPC3, and TNNT2 genes in Brazilian patients with
      hypertrophic cardiomyopathy.
AB  - BACKGROUND: Hypertrophic cardiomyopathy (HC) is the most prevalent genetic
      cardiac disease caused by a mutation in sarcomeres, Z-disks, or calcium-handling
      genes and is characterized by unexplained left ventricular hypertrophy. The aim
      of this study was to determine the genetic profile of Brazilian patients with HC
      and correlate the genotype with the phenotype. METHODS: We included 268 index
      patients from Sao Paulo city and 3 other cities in Brazil and extracted their DNA
      from whole blood. We amplified the coding sequencing of MYH7, MYBPC3, and TNNT2
      genes and sequenced them with an automatic sequencer. RESULTS: We identified
      causal mutations in 131 patients (48.8%). Seventy-eight (59.5%) were in the MYH7
      gene, 50 (38.2%) in the MYBPC3 gene, and 3 (2.3%) in the TNNT2 gene. We
      identified 69 mutations, 24 not previously described. Patients with an identified
      mutation were younger at diagnosis and at current age, had a higher mean heart
      rate and higher nonsustained ventricular tachycardia frequency compared with
      those without a mutation. Patients with MYH7 gene mutations had a larger left
      atrium and higher frequency of atrial fibrillation than did patients with MYBPC3
      gene mutations. CONCLUSION: The presence of a mutation in one of the genes
      suggests a worse prognosis. Mutations in the MYH7 gene, rather than in the MYBPC3
      gene, were also related to a worse prognosis. This is the first work
      characterizing HC molecular epidemiology in the Brazilian population for the 3
      most important genes.

PMID- 24093861
TI  - Impact of choice of imaging modality accompanying outpatient exercise stress
      testing on outcomes and resource use after revascularization for acute coronary
      syndromes.
AB  - BACKGROUND: Exercise stress testing is commonly obtained after percutaneous
      coronary intervention (PCI) performed for acute coronary syndromes (ACS). We
      compared the relationships between exercise echocardiography and nuclear testing
      after ACS-related PCI on outcomes and resource use. METHODS: Longitudinal
      observational study using fee-for-service Medicare claims to identify patients
      undergoing outpatient exercise stress testing with imaging within 15 months after
      PCI performed for ACS between 2003 and 2004. RESULTS: Of 63,100 patients
      undergoing stress testing 3 to 15 months post-PCI, 31,731 (50.3%) underwent an
      exercise stress test with imaging. Among 29,279 patients undergoing exercise
      stress testing with imaging, 15.5% received echocardiography. Echocardiography
      recipients had higher rates of repeat stress testing (adjusted hazard ratio [HR]
      2.60, CI 2.19-3.10) compared with those undergoing nuclear imaging in the 90 days
      after testing, but lower rates of revascularization (adjusted HR 0.87, CI 0.76
      0.98) and coronary angiography (adjusted HR 0.88, CI 0.80-0.97). None of these
      differences persisted subsequent to 90 days after stress testing. Rates of death
      and readmission for myocardial infarction rates were similar. Total Medicare
      payments were lower initially after echocardiography (incremental difference
      $498, CI 488-507), an effect attributed primarily to lower reimbursement for the
      stress test itself, but not significantly different after 14 months after
      testing. CONCLUSIONS: In this study using administrative data, echocardiography
      recipients initially had fewer invasive procedures but higher rates of repeat
      testing than nuclear testing recipients. However, these differences between echo
      and nuclear testing did not persist over longer time frames.

PMID- 24093863
TI  - Testosterone treatment and exercise capacity.

PMID- 24093862
TI  - Racial differences in antilipemic use and lipid control in high-risk older
      adults: post-Medicare Part D.
AB  - BACKGROUND: Older blacks are less likely to receive guideline-recommended
      antilipemic therapy and achieve lipid control than older whites because, in part,
      of out-of-pocket costs. We sought to determine whether racial differences in
      antilipemic use and lipid control narrowed after Medicare Part D's
      implementation. METHODS: This before-after study included 1,091 black and white
      adults 70 years or older with coronary heart disease and/or diabetes mellitus
      from the Health Aging and Body Composition Study. Primary outcomes were
      antilipemic use and low-density lipoprotein cholesterol control. Key independent
      variables were race, time (pre-Part D vs post-Part D), and their interaction.
      RESULTS: Before Part D, fewer blacks than whites reported taking an antilipemic
      (32.70% vs 49.35%), and this difference was sustained after Part D (blacks 48.30%
      vs whites 64.57%). Multivariable generalized estimating equations confirmed no
      post-Part D change in racial differences in antilipemic use (adjusted ratio of
      the odds ratio 1.07, 95% CI 0.79-1.45). Compared with whites, more blacks had
      poor lipid control both before Part D (24.30% vs 12.36%, respectively) and after
      Part D (24.46% vs 13.72%, respectively), with no post-Part D change in racial
      differences in lipid control (adjusted ratio of the odds ratio 0.82, 95% CI 0.51
      1.33). CONCLUSION: Although antilipemic use increased after Medicare Part D for
      both races, this policy change was associated with a change neither in lipid
      control for either racial group nor in the racial differences in antilipemic use
      or lipid control.

PMID- 24093864
TI  - Exercise and testosterone supplementation in male chronic heart failure patients
      with low testosterone status.

PMID- 24093865
TI  - Liberal versus restrictive transfusion strategy for patients with coronary artery
      disease.

PMID- 24093866
TI  - Response to Dr Sandar et al.

PMID- 24093867
TI  - Neointimal reaction in overlap segments of drug-eluting stents: is it "one-size
      fits-all"?

PMID- 24093868
TI  - Iron deficiency as a good potential prediction of chronic heart failure.

PMID- 24093869
TI  - Value of systolic right ventricular function parameters in children with
      pulmonary arterial hypertension associated with congenital heart diseases.

PMID- 24093870
TI  - Reply to Koestenberger and Ravekes.

PMID- 24093871
TI  - Letter to the editor regarding "prevalence and clinical outcomes of undiagnosed
      diabetes mellitus and prediabetes among patients with high-risk non-ST-segment
      elevation acute coronary syndrome".

PMID- 24093872
TI  - Responding to the letter to the editor by Saver.

PMID- 24093873
TI  - Recovering a representative conformational ensemble from underdetermined
      macromolecular structural data.
AB  - Structural analysis of proteins and nucleic acids is complicated by their
      inherent flexibility, conferred, for example, by linkers between their contiguous
      domains. Therefore, the macromolecule needs to be represented by an ensemble of
      conformations instead of a single conformation. Determining this ensemble is
      challenging because the experimental data are a convoluted average of
      contributions from multiple conformations. As the number of the ensemble degrees
      of freedom generally greatly exceeds the number of independent observables,
      directly deconvolving experimental data into a representative ensemble is an ill
      posed problem. Recent developments in sparse approximations and compressive
      sensing have demonstrated that useful information can be recovered from
      underdetermined (ill-posed) systems of linear equations by using sparsity
      regularization. Inspired by these advances, we designed the Sparse Ensemble
      Selection (SES) method for recovering multiple conformations from a limited
      number of observations. SES is more general and accurate than previously
      published minimum-ensemble methods, and we use it to obtain representative
      conformational ensembles of Lys48-linked diubiquitin, characterized by the
      residual dipolar coupling data measured at several pH conditions. These
      representative ensembles are validated against NMR chemical shift perturbation
      data and compared to maximum-entropy results. The SES method reproduced and
      quantified the previously observed pH dependence of the major conformation of
      Lys48-linked diubiquitin, and revealed lesser-populated conformations that are
      preorganized for binding known diubiquitin receptors, thus providing insights
      into possible mechanisms of receptor recognition by polyubiquitin. SES is
      applicable to any experimental observables that can be expressed as a weighted
      linear combination of data for individual states.

PMID- 24093876
TI  - An examination of the principles of influence on condom use decision making
      during casual sex encounters.
AB  - Cialdini's (1984) principles of influence were employed to inform the decision
      making process with respect to using condoms during casual sex. In the current
      study, focus groups (n = 9) were conducted to understand the relationship between
      the six principles of influence (authority, consistency, liking, reciprocity,
      scarcity, and social proof) and condom use in casual sex relationships. Results
      revealed that authority, consistency, and social proof were endorsed often as
      influencing condom use. Gender differences in the endorsement of the principles
      were also observed. The results speak to how these principles of influence aide
      the condom decision-making process during these often spontaneous sexual
      encounters and are discussed with an emphasis on the theoretical and practical
      implications for using these principles in future health campaigns. 

PMID- 24093877
TI  - Vaccines against Toxoplasma gondii: new developments and perspectives.
AB  - Toxoplasmosis caused by the protozoan Toxoplasma gondii is a major public health
      problem, infecting one-third of the world human beings, and leads to abortion in
      domestic animals. A vaccine strategy would be an ideal tool for improving disease
      control. Many efforts have been made to develop vaccines against T. gondii to
      reduce oocyst shedding in cats and tissue cyst formation in mammals over the last
      20 years, but only a live-attenuated vaccine based on the S48 strain has been
      licensed for veterinary use. Here, the authors review the recent development of
      T. gondii vaccines in cats, food-producing animals and mice, and present its
      future perspectives. However, a single or only a few antigen candidates revealed
      by various experimental studies are limited by only eliciting partial protective
      immunity against T. gondii. Future studies of T. gondii vaccines should include
      as many CTL epitopes as the live attenuated vaccines. 

PMID- 24093878
TI  - Severe hyponatremia following radioactive iodine therapy in patients with
      differentiated thyroid cancer.
AB  - BACKGROUND: Symptomatic hyponatremia in association with radioactive iodine (RAI)
      therapy for differentiated thyroid cancer has rarely been reported. Due to the
      increasing incidence of thyroid cancer worldwide, more patients are now receiving
      postoperative RAI therapy. We report two cases of life-threatening severe
      hyponatremia in association with RAI therapy. SUMMARY: Two elderly female
      patients who had bilateral thyroidectomies for their thyroid cancer underwent a
      low-iodine diet and levothyroxine withdrawal for two weeks prior to RAI therapy.
      Upon admission, the patients were given 130 mCi (4810 MBq) and 150 mCi (5550 MBq)
      of (131)I respectively, and oral hydration (two to three liters of water daily)
      to increase the frequency of emptying the bladder of RAI. Both patients completed
      their RAI therapy without significant complications and were discharged from
      hospital. Two days after discharge, both patients were admitted to the emergency
      room with complaints of severe nausea and dizziness. Initial laboratory tests
      revealed that they were in a hypothyroid state and had severe hyponatremia with a
      serum sodium level of 108 mEq/L. The symptomatic hyponatremia responded to
      intravenous hypertonic saline infusion and thyroid hormone replacement, and the
      patients made a full recovery. The low-iodine diet and hypothyroid state with
      overzealous hydration in the setting of RAI therapy may have provoked severe
      hypotonic hyponatremia. CONCLUSION: Hypothyroid patients after undergoing RAI
      therapy, especially the elderly, are at an increased risk for serious
      hyponatremia and should be monitored closely.

PMID- 24093880
TI  - Does working memory training lead to generalized improvements in children with
      low working memory? A randomized controlled trial.
AB  - Children with low working memory typically make poor educational progress, and it
      has been speculated that difficulties in meeting the heavy working memory demands
      of the classroom may be a contributory factor. Intensive working memory training
      has been shown to boost performance on untrained memory tasks in a variety of
      populations. This first randomized controlled trial with low working memory
      children investigated whether the benefits of training extend beyond standard
      working memory tasks to other more complex activities typical of the classroom in
      which working memory plays a role, as well as to other cognitive skills and
      developing academic abilities. Children aged 7-9 years received either adaptive
      working memory training, non-adaptive working memory training with low memory
      loads, or no training. Adaptive training was associated with selective
      improvements in multiple untrained tests of working memory, with no evidence of
      changes in classroom analogues of activities that tax working memory, or any
      other cognitive assessments. Gains in verbal working memory were sustained one
      year after training. Thus the benefits of working memory training delivered in
      this way may not extend beyond structured working memory tasks.

PMID- 24093881
TI  - Risk behaviors for HIV in sexual partnerships of San Francisco injection drug
      users.
AB  - While injection drug users (IDU) in the USA are known to form sexual partnerships
      with IDU as well as non-IDU, scientific research is lacking regarding risk
      behaviors for HIV transmission within these partnerships. Such information could
      aid HIV-prevention efforts among IDU and could also explain the relatively low
      prevalence of HIV among non-IDU heterosexuals in US cities such as San Francisco.
      Using data from a cross-sectional sample of San Francisco IDU we estimated (1)
      the prevalence of IDU-IDU and IDU-non-IDU sexual partnerships, (2) the frequency
      of serodiscordant unprotected intercourse in IDU-IDU and IDU-non-IDU sexual
      partnerships, and (3) the frequency of concurrence of sexual risk and injection
      related risk within IDU-IDU sexual partnerships. An estimated 68% of sexually
      active San Francisco IDU is in IDU-IDU partnerships. Our analysis suggests that
      compared to IDU-non-IDU partnerships, IDU-IDU partnerships include a greater rate
      of episodes of serodiscordant unprotected intercourse (incidence rate ratio:
      10.2; 95% confidence interval: 2.1-50.7). In fact, our data suggest that 92% of
      serodiscordant sexual episodes involving IDU are attributable to IDU-IDU
      pairings. Unprotected intercourse and needle sharing occur concurrently in an
      estimated 29% of IDU-IDU partnerships. Our data suggest that HIV-transmission
      risk is higher within IDU-IDU partnerships than it is within IDU-non-IDU
      partnerships. This disparity could explain the relatively low prevalence of HIV
      among non-IDU heterosexuals in San Francisco. We recommend that HIV-prevention
      efforts among IDU continue to address sexual risk behaviors for HIV transmission
      in addition to injection-related risk behaviors, with emphasis on IDU-IDU
      partnerships. 

PMID- 24093879
TI  - Temporal histological changes in lacrimal and major salivary glands in mouse
      models of Sjogren's syndrome.
AB  - BACKGROUND: Evidence in imaging studies suggests that there may be differences in
      glandular involvement in Sjogren's syndrome (SS) depending on the stage of the
      disease. No detailed histological studies are available to show if there are any
      such difference in glandular involvement at various time periods and stages of
      SS. This cross sectional study examines the inflammatory changes in mouse models
      of SS at various ages. METHODS: The histological changes in major salivary and
      lacrimal glands were studied at ages of 3, 6, 9, 12, 15 and 18 months in both
      sexes in well characterized mouse models of SS, non-obese diabetes mouse and
      Interleukin-14 alpha-transgenic mice. RESULTS: Our results indicate that early
      inflammation concurrently occur in submandibular and lacrimal glands around the
      age of 6 weeks. Parotid glands are involved much later in the course of SS with
      less severe inflammation. Sublingual glands are rarely involved. CONCLUSIONS: Our
      conclusions are that SS may be an organ specific disease with early inflammation
      occurring in submandibular and lacrimal glands, followed by the parotid. Non
      organ specific events occur in later courses of the disease. The understanding of
      the disease progression is important in tailoring early local therapeutic
      interventions before complete destruction of salivary and lacrimal glands.

PMID- 24093882
TI  - Amino acid capture by aqueous interfaces. Implications for biological uptake.
AB  - The interactions of natural amino acids with water-hydrophobic interfaces are
      central to the control of key biological processes, such as passive transport,
      and to the overall structure and stability of membrane proteins. We still have a
      very poor knowledge of these interactions, and our aim in this work is to
      investigate the thermochemistry and dynamics properties of simple aliphatic amino
      acids (glycine and valine) across a water-organic interface. The study has been
      carried out by means of Born-Oppenheimer molecular dynamics simulations focusing
      on the role that the hydrophobicity of the side chain has on the phase transfer
      mechanism of the amino acid. Data for the energetics of the uptake processes have
      been reported, and it is expected that the reported results will be helpful in
      the design of future experiments with systems of biological relevance. We have
      shown that neutral tautomers exhibit a noticeable affinity for the interface that
      increases with increasing hydrophobicity of the side chain. Moreover, the
      zwitterionic form of valine (but not that of glycine) does also exhibit a
      significant affinity for the interface. An important finding is that the neutral
      and zwitterionic tautomers are roughly isoergonic in the organic layer close to
      the interface. This result suggests a two-step mechanism for the water-to-organic
      phase transfer that involves neutralization of a partially hydrated zwitterion in
      the organic layer prior to uptake into the bulk. Though the mechanisms for
      glycine and valine are similar, the predicted energetics and dynamics for the
      first step display noteworthy differences that should be measurable and may have
      important biological implications. 

PMID- 24093883
TI  - Looking for trees in the forest: summary tree from posterior samples.
AB  - BACKGROUND: Bayesian phylogenetic analysis generates a set of trees which are
      often condensed into a single tree representing the whole set. Many methods exist
      for selecting a representative topology for a set of unrooted trees, few exist
      for assigning branch lengths to a fixed topology, and even fewer for
      simultaneously setting the topology and branch lengths. However, there is very
      little research into locating a good representative for a set of rooted time
      trees like the ones obtained from a BEAST analysis. RESULTS: We empirically
      compare new and known methods for generating a summary tree. Some new methods are
      motivated by mathematical constructions such as tree metrics, while the rest
      employ tree concepts which work well in practice. These use more of the posterior
      than existing methods, which discard information not directly mapped to the
      chosen topology. Using results from a large number of simulations we assess the
      quality of a summary tree, measuring (a) how well it explains the sequence data
      under the model and (b) how close it is to the "truth", i.e to the tree used to
      generate the sequences. CONCLUSIONS: Our simulations indicate that no single
      method is "best". Methods producing good divergence time estimates have poor
      branch lengths and lower model fit, and vice versa. Using the results presented
      here, a user can choose the appropriate method based on the purpose of the
      summary tree.

PMID- 24093884
TI  - Association between South African high-school learners' knowledge about
      tuberculosis and their intention to seek healthcare.
AB  - BACKGROUND: South Africa has one of the highest prevalence of tuberculosis (TB).
      Addressing awareness among school learners on TB transmission and prevention may
      assist in reducing the disease burden. OBJECTIVE: We report on factors associated
      with high-school learners' intentions to seek healthcare for TB. DESIGN: A survey
      testing TB symptoms, transmission, prevention knowledge, and intention to seek
      and adhere to treatment was conducted among 1,114 high-school learners in KwaZulu
      Natal (KZN), South Africa. Multivariate models correcting for nesting of students
      within schools tested associations between demographics, TB symptoms,
      transmission, prevention knowledge, and intention to seek and adhere to
      treatment. RESULTS: Learners knowing that coughing for more than 3 weeks (OR:
      2.33; 95% CI: 1.35-4.00) and night sweats (OR: 3.12; 95% CI: 1.80-5.41) were TB
      symptoms, TB is transmitted when a person with TB coughs (OR: 1.56; 95% CI: 1.23
      1.98), and coughing in a closed room was an incorrect practice for someone with
      TB (OR: 1.71; 95% CI: 1.05-2.78) were significantly more likely to intend taking
      family members for treatment. Learners knowing that coughing for more than 3
      weeks (OR: 2.69; 95% CI: 1.19-6.09), coughing blood (OR: 2.24; 95% CI: 1.33
      3.76), and night sweats (OR: 2.25; 95% CI: 1.09-4.64) were TB symptoms, were
      significantly more likely to intend encouraging family members to adhere to TB
      treatment. Learners knowing that coughing for more than 3 weeks (OR: 1.47; 95%
      CI: 1.05-2.07), coughing blood (OR: 2.08; 95% CI: 1.44-3.01), and weight loss
      (OR: 1.85; 95% CI: 1.38-2.49) were TB symptoms, were significantly more likely to
      intend taking TB treatment if symptomatic. Learners knowing that coughing for
      more than 3 weeks (OR: 2.04; 95% CI: 1.45-2.87), and coughing blood (OR: 1.81;
      95% CI: 1.24-2.62), were TB symptoms were significantly more likely to intend
      adhering to TB treatment. CONCLUSIONS: High-school learners with knowledge about
      TB symptoms, transmission, and prevention have positive intentions to seek
      treatment for themselves and family members and adhere to treatment.

PMID- 24093885
TI  - Constraints faced by urban poor in managing diabetes care: patients' perspectives
      from South India.
AB  - BACKGROUND: Four out of five adults with diabetes live in low- and middle-income
      countries (LMIC). India has the second highest number of diabetes patients in the
      world. Despite a huge burden, diabetes care remains suboptimal. While patients
      (and families) play an important role in managing chronic conditions, there is a
      dearth of studies in LMIC and virtually none in India capturing perspectives and
      experiences of patients in regard to diabetes care. OBJECTIVE: The objective of
      this study was to better understand constraints faced by patients from urban
      slums in managing care for type 2 diabetes in India. DESIGN: We conducted in
      depth interviews, using a phenomenological approach, with 16 type 2- diabetes
      patients from a poor urban neighbourhood in South India. These patients were
      selected with the help of four community health workers (CHWs) and were
      interviewed by two trained researchers exploring patients' experiences of living
      with and seeking care for diabetes. The sampling followed the principle of
      saturation. Data were initially coded using the NVivo software. Emerging themes
      were periodically discussed among the researchers and were refined over time
      through an iterative process using a mind-mapping tool. RESULTS: Despite an
      abundance of healthcare facilities in the vicinity, diabetes patients faced
      several constraints in accessing healthcare such as financial hardship, negative
      attitudes and inadequate communication by healthcare providers and a fragmented
      healthcare service system offering inadequate care. Strongly defined gender-based
      family roles disadvantaged women by restricting their mobility and autonomy to
      access healthcare. The prevailing nuclear family structure and inter-generational
      conflicts limited support and care for elderly adults. CONCLUSIONS: There is a
      need to strengthen primary care services with a special focus on improving the
      availability and integration of health services for diabetes at the community
      level, enhancing patient centredness and continuity in delivery of care. Our
      findings also point to the need to provide social services in conjunction with
      health services aiming at improving status of women and elderly in families and
      society.

PMID- 24093887
TI  - Asymmetric N-heterocyclic carbene (NHC)-catalyzed annulation of modified enals
      with enolizable aldehydes.
AB  - N-Heterocyclic carbene (NHC)-catalyzed highly enantioselective lactonization of
      modified enals with enolizable aldehydes, proceeding via the alpha,beta
      unsaturated acylazolium intermediates, is reported. The reaction results in the
      asymmetric synthesis of synthetically important 4,5-disubstituted
      dihydropyranones. 

PMID- 24093886
TI  - Validity of self-measured waist and hip circumferences: results from a community
      study in Malaysia.
AB  - BACKGROUND: Measures of central adiposity are better predictors of adverse health
      events than BMI. Nonetheless, BMI is more widely used in health research. One
      reason for this may be the limited research supporting the self-measurement of
      waist and hip circumference. The lack of validity studies is particularly acute
      in Asia. The main objective was to establish the validity of self-measurement of
      waist and hip circumference in a community setting and the correlation of those
      measures with BMI, blood pressure, and blood glucose levels. METHODS: A community
      based, cross-sectional survey. A "healthy living expo" at a shopping mall in a
      rural town on peninsular Malaysia One hundred and thirty six (136) individuals
      volunteered to participate in the study, 125 of whom met the inclusion criteria.
      The ethnic distribution of the participants was 80% Chinese, 17% Malay and 3%
      Indian. Most participants were female (60%), with participants' ages ranging from
      18 to 78 years (mean, 47.2). Self and assisted measurements of waist and hip were
      taken. Blood pressure, non-fasting blood glucose, height, and weight were also
      measured. Bland Altman plots and Lin's concordance coefficient were used to
      measure agreement between self and assisted measures. Pearson's correlation was
      used to examine the association of self and assisted measures with blood
      pressure, blood glucose, and BMI. RESULTS: There was a downwards bias in self
      measured waist (-0.81 cm) and hip (-1 cm) circumferences compared with assisted
      measures. The concordance for the self and assisted measures of waist, hip and
      the ratio of the two were, respectively, .96, .93 , and .84. The correlation
      between measures of central adiposity and BMI, blood pressure and blood glucose
      were similar for self and assisted measures. CONCLUSION: The results provide
      additional support for the use of self-measurement of waist and hip circumference
      studies of central adiposity, but is limited by the specificity of the setting.

PMID- 24093888
TI  - Stability of parenteral nanoemulsions loaded with paclitaxel: the influence of
      lipid phase composition, drug concentration and storage temperature.
AB  - Paclitaxel was loaded into licensed parenteral nutrition nanoemulsions
      (Clinoleic(r) and Intralipid(r)) using bath sonication, and the stability of the
      formulations was investigated following storage for two weeks at room temperature
      or at 4  degrees C. In general, Clinoleic droplets were smaller than Intralipid
      droplets, being around 255 and 285 nm, respectively, for blank and freshly loaded
      emulsions. Regardless of storage temperature, the Clinoleic exhibited a very
      slight or no increase in droplet size upon storage, whilst the droplet size of
      the Intralipid emulsion increased significantly. The droplet size of both
      emulsions was minimally affected by paclitaxel concentration within the range of
      0, 1, 3 and 6 mg/ml. The pH of both emulsions markedly decreased upon storage at
      room temperature, which was possibly attributed to the production of fatty acids
      resulting from phospholipid hydrolysis. However, at 4  degrees C, the pH of
      Clinoleic emulsion was unaffected by storage or paclitaxel concentration while
      the Intralipid emulsion demonstrated a trend for pH reduction. Both nanoemulsions
      had a negative zeta potential, with the Clinoleic formulations having the highest
      charge, possibly explaining the better size stability of this emulsion. Overall,
      this study has shown that paclitaxel was successfully loaded into clinically
      licensed parenteral emulsions and that Clinoleic showed greater stability than
      the Intralipid.

PMID- 24093890
TI  - Controlled formation of silica structures using siloxane/block copolymer
      complexes prepared in various solvent mixtures.
AB  - Block copolymers exhibit regularly patterned structures induced by microphase
      separation. Here we present a method for preparing various particulate silica
      (SiO2) nanostructures by controlling the microphase separation of block
      copolymers. In this method, siloxane, a SiO2 precursor, is adsorbed onto poly(4
      vinylpyridine) blocks of polystyrene-block-poly(4-vinylpyridine) in solvent
      mixtures. After siloxane/polymer complexes are coprecipitated via further
      siloxane polycondensation, the resulting precipitates are heated to remove the
      polymer. The results of scanning electron microscopy revealed that SiO2 formed
      various structures including cylindrical, spherical, and lamellar. Different SiO2
      nanostructures formed via the microphase separation of siloxane/polymer complexes
      are prepared simply by varying solvent mixtures without changing the polymer
      chain. The structural change is interpreted in terms of polymer-solvent
      interactions and volume fractions in siloxane/polymer complexes. 

PMID- 24093889
TI  - Screening of key genes in gastric cancer with DNA microarray analysis.
AB  - BACKGROUND: The aim of this study was to identify key genes and novel potential
      therapeutic targets related to gastric cancer (GC) by comparing cancer tissue
      samples and healthy control samples using DNA microarray analysis. METHODS:
      Microarray data set GSE19804 was downloaded from Gene Expression Omnibus.
      Preprocessing and differential analysis were conducted with of R statistical
      software packages, and a number of differentially expressed genes (DEGs) were
      obtained. Cluster analysis was also done with gene expression values. Functional
      enrichment analysis was performed for all the DEGs with DAVID tools. The
      significantly up- and downregulated genes were selected out and their interactors
      were retrieved with STRING and HitPredict, followed by construction of networks.
      For all the genes in the two networks, GeneCodis was chosen for gene function
      annotation. RESULTS: A total of 638 DEGs were identified, and we found that SPP1
      and FABP4 were the markedly up- and downregulated genes, respectively. Cell cycle
      and regulation of proliferation were the most significantly overrepresented
      functional terms in up- and downregulated genes. In addition, extracellular
      matrix-receptor interaction was found to be significant in the SPP1-included
      interaction network. CONCLUSIONS: A range of DEGs were obtained for GC. These
      genes not only provided insights into the pathogenesis of GC but also could
      develop into biomarkers for diagnosis or treatment.

PMID- 24093891
TI  - Bendamustine: a bridge to longer term solutions in heavily treated Hodgkin
      lymphoma.

PMID- 24093892
TI  - Chemical mustard containment using simple palladium pincer complexes: the
      influence of molecular walls.
AB  - Six amide-based NNN palladium(II) pincer complexes Pd(L)(CH3CN) were synthesized,
      characterized, and examined for binding the sulfur mustard surrogate, 2
      chloroethyl ethyl sulfide (CEES). The complexes all bind readily with CEES as
      shown by (1)H NMR spectroscopy in CDCl3. The influence of para-substituents on
      the two amide phenyl appendages was explored as well as the effect of replacing
      the phenyl groups with larger aromatic rings, 1-naphthalene and 9-anthracene.
      While variations of the para-substituents had only a slight influence on the
      binding affinities, incorporation of larger aromatic rings resulted in a
      significant size-related increase in binding, possibly due to increasing steric
      and electronic interactions. In crystal structures of three CEES-bound complexes,
      the mustard binds through the sulfur atom and lies along the aromatic walls of
      the side appendages approximately perpendicular to the pincer plane, with
      increasingly better alignment progressing from phenyl to 1-naphthalene to 9
      anthracene. 

PMID- 24093893
TI  - Acute bronchiolitis.
AB  - Bronchiolitis is the most common lower respiratory tract infection to affect
      infants and toddlers. High-risk patients include infants younger than 3 months,
      premature infants, children with immunodeficiency, children with underlying
      cardiopulmonary or neuromuscular disease, or infants prone to apnea, severe
      respiratory distress, and respiratory failure. Bronchiolitis is a self-limited
      disease in healthy infants and children. Treatment is usually symptomatic, and
      the goal of therapy is to maintain adequate oxygenation and hydration. Use of a
      high-flow nasal cannula is becoming common for children with severe
      bronchiolitis.

PMID- 24093894
TI  - Asthma update.
AB  - Asthma continues to be one of the most common reasons for emergency department
      visits and a leading cause of hospitalization. Acute management involves severity
      based treatment of bronchoconstriction and underlying airway inflammation.
      Optimal treatment has been defined and standardized through randomized controlled
      trials, systematic reviews, and consensus guidelines. Implementation of clinical
      practice guidelines may improve clinical, quality, and safety outcomes. Asthma
      morbidity is disproportionately high in poor, urban, and minority children.
      Children treated in emergency departments commonly have persistent chronic
      severity, significant morbidity, and infrequent follow-up and primary asthma
      care, and prescription of inhaled corticosteroids is appropriate. 

PMID- 24093895
TI  - Evaluation of child with fever without source: review of literature and update.
AB  - Fever is one of the most common reasons for a visit to the primary care provider
      or the emergency department. Traditionally, clinicians have used various risk
      stratification strategies to identify serious bacterial infections (SBI) without
      an obvious source in febrile children, because missed bacterial infections in
      such children can result in meningitis, sepsis, and death; therefore, early and
      accurate identification of SBIs is critical. Infants aged less than 60 to 90 days
      are at greatest risk of SBI. The epidemiology of SBI continues to evolve,
      especially after the successful introduction of conjugate vaccines against
      Streptococcus pneumoniae and Haemophilus influenzae.

PMID- 24093896
TI  - Skin and soft tissue infections.
AB  - The approach to common skin and soft tissue infections (SSTIs) was previously
      well understood. However, the recent emergence of community-associated
      methicillin resistant Staphyloccocus aureus as a common pathogen has changed the
      epidemiology of these infections and has led clinicians to alter their practice
      and treatment of SSTI. This article discusses the present epidemiology of SSTI
      and community-acquired methicillin-resistant Staphylococcus aureus, evidence
      based approach to incision and drainage, the utility of adjuvant antibiotic
      therapy after abscess drainage, and current antimicrobial approach to cellulitis
      and nondrained SSTIs. Methods to reduce transmission and recurrence of SSTI
      through decolonization strategies are also discussed. 

PMID- 24093897
TI  - Approach to syncope and altered mental status.
AB  - Children who present with an episode of altered mental status, whether transient
      or persistent, present a diagnostic challenge for practitioners. This article
      describes some of the more common causes of altered mental status and delineates
      a rational approach to these patients. This will help practitioners recognize the
      life-threatening causes of these frightening presentations as well as help avoid
      unnecessary testing for the more benign causes. 

PMID- 24093898
TI  - Updates in the general approach to pediatric head trauma and concussion.
AB  - Acute recognition and management of traumatic brain injury along the spectrum
      from mild to severe is essential in optimizing neurocognitive outcomes.
      Concussion is common following head trauma in children, and resulting symptoms
      can last for months if not diagnosed and managed properly. Emerging evidence and
      consensus demonstrate that a program of cognitive and physical activity with a
      graduated return to play, sport, and school may improve outcomes following
      concussion. "Return to Play" legislation for youth has been adopted by most
      states. Outcomes of patients with severe traumatic brain injury have improved. 

PMID- 24093899
TI  - Cervical spine injury.
AB  - Once a child is determined to be at risk of having a cervical spine injury,
      clinicians must take appropriate precautions to avoid potential worsening of
      neurologic deficits. Occasionally these decisions are made in the absence of
      adequate cervical spine imaging when dealing with a child's unstable airway or
      other life-threatening injuries. Furthermore, clinicians have to make decisions
      regarding appropriate diagnostic testing to evaluate for potential injury.
      Decisions regarding testing should take into consideration the clinical
      presentation of the patient, aiming to order appropriate testing for those at
      risk and avoid unnecessary testing for those without signs of cervical spine
      injury. 

PMID- 24093900
TI  - Emerging concepts in pediatric emergency radiology.
AB  - Radiologic studies are a vital component in the workup and diagnosis of disease.
      An appropriate radiographic study will accurately rule in or rule out disease
      with the least possible harm. Special considerations are necessary for the
      imaging of children. Current trends in pediatric imaging support the increased
      use of ultrasound and magnetic resonance imaging to decrease radiation exposure.
      In this review, we highlight some of the emerging concepts in the radiographic
      workup of pediatric disease, with a focus on decreasing ionizing radiation,
      increasing ultrasound use, and using clinical decision rules to identify children
      who do not need imaging. 

PMID- 24093901
TI  - Pediatric office emergencies.
AB  - Pediatricians regularly see emergencies in the office, or children that require
      transfer to an emergency department, or hospitalization. An office self
      assessment is the first step in determining how to prepare for an emergency. The
      use of mock codes and skill drills make office personnel feel less anxious about
      medical emergencies. Emergency information forms provide valuable, quick
      information about complex patients for emergency medical services and other
      physicians caring for patients. Furthermore, disaster planning should be part of
      an office preparedness plan. 

PMID- 24093902
TI  - Common office procedures and analgesia considerations.
AB  - This article reviews common office procedures and analgesia considerations for
      pediatric outpatients. Layer times of onset of analgesics to coincide with
      procedures. Pediatric procedural distress is multimodal. Always address parent
      and child fear and attention, along with pain.

PMID- 24093904
TI  - Updates in the general approach to the pediatric poisoned patient.
AB  - Poison prevention remains essential to prevent the most vulnerable population
      from becoming exposed to potentially lethal toxins. The evaluation of a child
      presumed to have been exposed to a toxic substance should include a precise
      history of the exposure, a physical examination, and knowledge of current
      ingestions and recreational practices. New treatments and research guiding
      therapy continue to evolve. Poison centers and medical toxicologists can be
      consulted to assist with the diagnosis of medicinal/drug overdoses, for advice
      about the pitfalls inherent in stabilizing children who have been exposed to
      toxic compounds, and for treatment recommendations based on the latest research. 

PMID- 24093903
TI  - Pediatric mental health emergencies and special health care needs.
AB  - Children with mental health problems are increasingly being evaluated and treated
      by both pediatric primary care and pediatric emergency physicians. This article
      focuses on the epidemiology, evaluation, and management of the 2 most common
      pediatric mental health emergencies, suicidal and homicidal/aggressive patients,
      as well as the equally challenging population of children with autism or other
      developmental disabilities. 

PMID- 24093905
TI  - Updates in pediatric gastrointestinal foreign bodies.
AB  - Although most ingested foreign bodies in children pass spontaneously, certain
      foreign bodies can be harmful and they require special attention and emergent
      medical intervention to prevent significant morbidity and mortality. This article
      presents an overview of the epidemiology, diagnosis, management, and
      complications of foreign body ingestions in children. Particular attention is
      paid to coins, sharp objects, long objects, food bolus, caustic liquids,
      batteries, and magnets. 

PMID- 24093906
TI  - Injury prevention: opportunities in the emergency department.
AB  - Because injury is the leading cause of morbidity and mortality in young patients,
      emergency departments have a significant opportunity to provide injury-prevention
      interventions at a teachable moment. The emergency department has the ability to
      survey injuries in the community, use the hospital setting to screen patients,
      provide products, offer resources to assist families within this setting to
      change their risky behaviors, and connect families to community resources. With a
      thoughtful, collaborative approach, emergency departments are an excellent
      setting within which to promote injury prevention among patients and families. 

PMID- 24093907
TI  - Pediatric emergencies.

PMID- 24093908
TI  - Targeting thymidylate synthase in colorectal cancer: critical re-evaluation and
      emerging therapeutic role of raltitrexed.
AB  - INTRODUCTION: 5-fluorouracil continues to be the cornerstone of treatment for
      colorectal cancer. Although fluoropyrimidines are generally considered as well
      tolerated drugs, severe toxicities can be a major clinical problem, and the
      recommended prolonged infusion of 5-fluorouracil provokes discomfort in patients.
      Raltitrexed (Tomudex), a quinazoline analogue of folinic acid, is a selective and
      direct thymidylate synthase (TS) inhibitor with a convenient 3-weekly schedule of
      administration. AREAS COVERED: In this review, through critical insight into the
      mechanism of action and main clinical experiences, the authors suggest the
      necessity to reconsider raltitrexed as a valuable anticancer drug and as a
      suitable option for colorectal cancer. The authors highlight its emerging
      therapeutic role in clinical practice for patients with fluoropyrimidine-induced
      cardiotoxicity or a significant history of cardiac disease. EXPERT OPINION: This
      review discusses if TS could still be a relevant target for colorectal cancer in
      the era of molecular therapy and if raltitrexed should still be considered a drug
      with a life-threatening toxicity. Furthermore, this review discusses the
      principal combination clinical experiences of raltitrexed and its emerging
      therapeutic role in clinical practice as a suitable option for colorectal cancer
      patients with fluoropyrimidine-induced cardiotoxicity or a significant history of
      cardiac disease.

PMID- 24093909
TI  - A CMV vaccine: TREATing despite the TRICKs.

PMID- 24093910
TI  - Integrating and extending cohort studies: lessons from the eXtending Treatments,
      Education and Networks in Depression (xTEND) study.
AB  - BACKGROUND: Epidemiologic studies often struggle to adequately represent
      populations and outcomes of interest. Differences in methodology, data analysis
      and research questions often mean that reviews and synthesis of the existing
      literature have significant limitations. The current paper details our
      experiences in combining individual participant data from two existing cohort
      studies to address questions about the influence of social factors on health
      outcomes within a representative sample of urban to remote areas of Australia.
      The eXtending Treatments, Education and Networks in Depression study involved
      pooling individual participant data from the Australian Rural Mental Health Study
      (T0 N = 2639) and the Hunter Community Study (T0 N = 3253) as well as conducting
      a common three-year follow-up phase (T1 N = 3513). Pooling these data extended
      the capacity of these studies by: enabling research questions of common interest
      to be addressed; facilitating the harmonization of baseline measures; permitting
      investigation of a range of psychosocial, physical and contextual factors over
      time; and contributing to the development and implementation of targeted
      interventions for persons experiencing depression and alcohol issues. DISCUSSION:
      The current paper describes the rationale, challenges encountered, and solutions
      devised by a project aiming to maximise the benefits derived from existing cohort
      studies. We also highlight opportunities for such individual participant data
      analyses to assess common assumptions in research synthesis, such as measurement
      invariance, and opportunities for extending ongoing cohorts by conducting a
      common follow-up phase. SUMMARY: Pooling individual participant data can be a
      worthwhile venture, particularly where adequate representation is beyond the
      scope of existing research, where the effects of interest are small though
      important, where events are of relatively low frequency or rarely observed, and
      where issues are of immediate regional or national interest. Benefits such as
      these can enhance the utility of existing projects and strengthen requests for
      further research funding.

PMID- 24093913
TI  - Genome-wide DNA polymorphisms in two cultivars of mei (Prunus mume sieb. et
      zucc.).
AB  - BACKGROUND: Mei (Prunus mume Sieb. et Zucc.) is a famous ornamental plant and
      fruit crop grown in East Asian countries. Limited genetic resources, especially
      molecular markers, have hindered the progress of mei breeding projects. Here, we
      performed low-depth whole-genome sequencing of Prunus mume 'Fenban' and Prunus
      mume 'Kouzi Yudie' to identify high-quality polymorphic markers between the two
      cultivars on a large scale. RESULTS: A total of 1464.1 Mb and 1422.1 Mb of
      'Fenban' and 'Kouzi Yudie' sequencing data were uniquely mapped to the mei
      reference genome with about 6-fold coverage, respectively. We detected a large
      number of putative polymorphic markers from the 196.9 Mb of sequencing data
      shared by the two cultivars, which together contained 200,627 SNPs, 4,900 InDels,
      and 7,063 SSRs. Among these markers, 38,773 SNPs, 174 InDels, and 418 SSRs were
      distributed in the 22.4 Mb CDS region, and 63.0% of these marker-containing CDS
      sequences were assigned to GO terms. Subsequently, 670 selected SNPs were
      validated using an Agilent's SureSelect solution phase hybridization assay. A
      subset of 599 SNPs was used to assess the genetic similarity of a panel of mei
      germplasm samples and a plum (P. salicina) cultivar, producing a set of
      informative diversity data. We also analyzed the frequency and distribution of
      detected InDels and SSRs in mei genome and validated their usefulness as DNA
      markers. These markers were successfully amplified in the cultivars and in their
      segregating progeny. CONCLUSIONS: A large set of high-quality polymorphic SNPs,
      InDels, and SSRs were identified in parallel between 'Fenban' and 'Kouzi Yudie'
      using low-depth whole-genome sequencing. The study presents extensive data on
      these polymorphic markers, which can be useful for constructing high-resolution
      genetic maps, performing genome-wide association studies, and designing genomic
      selection strategies in mei.

PMID- 24093914
TI  - Predicting cancer risk knowledge and information seeking: the role of social and
      cognitive factors.
AB  - This study tests an expanded Structural Influence Model (SIM) to gain a greater
      understanding of the social and cognitive factors that contribute to disparities
      in cancer risk knowledge and information seeking. At the core of this expansion
      is the planned risk information seeking model (PRISM). This study employed an
      online sample (N = 1,007) of African American, Hispanic, and non-Hispanic White
      adults. The addition of four cognitive predictors to the SIM substantially
      increased variance explained in cancer risk knowledge (R(2) = .29) and
      information seeking (R(2) = .56). Health literacy mediated the effects of social
      determinants (socioeconomic status [SES] and race/ethnicity) on cancer risk
      knowledge, while subjective norms mediated their effects on cancer risk
      information seeking. Social capital and perceived seeking control were also shown
      to be important mediators of the relationships between SES and cancer
      communication outcomes. Our results illustrate the social and cognitive
      mechanisms by which social determinants impact cancer communication outcomes, as
      well as several points of intervention to reduce communication disparities. 

PMID- 24093915
TI  - Blood pressure self-measurement in the obstetric waiting room.
AB  - BACKGROUND: Pregnant diabetic patients are often required to self-measure their
      blood pressure in the waiting room before consultation. Currently used blood
      pressure devices do not guarantee valid measurements when used unsupervised. This
      could lead to misdiagnosis and treatment error. The aim of this study was to
      investigate current use of blood pressure self-measurement in the waiting room in
      order to identify challenges that could influence the resulting data quality.
      Also, we wanted to investigate the potential for addressing these challenges with
      e-health and telemedicine technology. SUBJECTS AND METHODS: We observed 81
      pregnant diabetics' ability to correctly self-measure in the waiting room during
      a 4-week observational descriptive study. Specifically, we investigated the level
      of patient adherence to six recommendations with which patients are instructed to
      comply in order to obtain a reliable blood pressure reading. RESULTS: We found
      that the patients did not adhere to given instructions when performing blood
      pressure self-measurement in the waiting room. None of the 81 patients adhered to
      all six investigated recommendations, while around a quarter adhered to five out
      of six of the recommendations. The majority followed four or fewer of the
      recommendations. CONCLUSIONS: Results indicate that unsupervised self-measurement
      of blood pressure is not a reliable method. Thus, there is a need for increased
      staff presence and patient training or, alternatively, for introducing improved
      technology support. This could include context-aware patient adherence aids and
      clinical decision support systems for automatically validating self-measured data
      based on e-health and telemedicine technology.

PMID- 24093916
TI  - Emergency department physician telemedical triage.
AB  - BACKGROUND: Telemedical physician triage (TPT) is a potential application of
      telemedicine in the emergency department (ED). We report the technical success,
      patient satisfaction, and effect on ED throughput metrics (length of stay [LOS]
      and time to physician evaluation [TPE]) of TPT performed on a mobile platform.
      MATERIALS AND METHODS: Patients underwent standard nursing triage with or without
      TPT. Technical success is reported as raw data. Patient satisfaction is reported
      as raw data+/-standard deviation on a 5-point (low-to-high) scale. LOS and TPE
      are reported as mean+/-SD [95% CI] values. Statistical analyses of LOS and TPE
      are via two-sample t test. RESULTS: One hundred six patients were registered
      during intervention periods, and TPT was completed in 36 (34%). One hundred
      ninety-six patients were registered during control periods. The technical success
      rate was 95%. Average patient satisfaction was 4.7 on a 5-point scale. The
      primary analysis (106 patients) showed no change in LOS (266+/-101 [244-288] min
      versus 258+/-172 [234-282] min) but a trend toward improved TPE with TPT (35+/-28
      [29-41] min versus 42+/-31 [38-46] min) (p=0.052). A secondary analysis (36
      patients) showed no change in LOS (273+/-125 [231-316] min versus 258+/-172 [234
      282] min) but improved TPE with TPT (16+/-15 [11-21] min versus 42+/-31 [38-46]
      min) (p<0.0001). CONCLUSIONS: TPT in the ED on a mobile platform was technically
      successful, well accepted by patients, and associated with a decrease in TPE but
      not LOS.

PMID- 24093917
TI  - Statistical strategies for constructing health risk models with multiple
      pollutants and their interactions: possible choices and comparisons.
AB  - BACKGROUND: As public awareness of consequences of environmental exposures has
      grown, estimating the adverse health effects due to simultaneous exposure to
      multiple pollutants is an important topic to explore. The challenges of
      evaluating the health impacts of environmental factors in a multipollutant model
      include, but are not limited to: identification of the most critical components
      of the pollutant mixture, examination of potential interaction effects, and
      attribution of health effects to individual pollutants in the presence of
      multicollinearity. METHODS: In this paper, we reviewed five methods available in
      the statistical literature that are potentially helpful for constructing
      multipollutant models. We conducted a simulation study and presented two data
      examples to assess the performance of these methods on feature selection, effect
      estimation and interaction identification using both cross-sectional and time
      series designs. We also proposed and evaluated a two-step strategy employing an
      initial screening by a tree-based method followed by further dimension
      reduction/variable selection by the aforementioned five approaches at the second
      step. RESULTS: Among the five methods, least absolute shrinkage and selection
      operator regression performs well in general for identifying important exposures,
      but will yield biased estimates and slightly larger model dimension given many
      correlated candidate exposures and modest sample size. Bayesian model averaging,
      and supervised principal component analysis are also useful in variable selection
      when there is a moderately strong exposure-response association. Substantial
      improvements on reducing model dimension and identifying important variables have
      been observed for all the five statistical methods using the two-step modeling
      strategy when the number of candidate variables is large. CONCLUSIONS: There is
      no uniform dominance of one method across all simulation scenarios and all
      criteria. The performances differ according to the nature of the response
      variable, the sample size, the number of pollutants involved, and the strength of
      exposure-response association/interaction. However, the two-step modeling
      strategy proposed here is potentially applicable under a multipollutant framework
      with many covariates by taking advantage of both the screening feature of an
      initial tree-based method and dimension reduction/variable selection property of
      the subsequent method. The choice of the method should also depend on the goal of
      the study: risk prediction, effect estimation or screening for important
      predictors and their interactions.

PMID- 24093918
TI  - Uptake and mitochondrial dysfunction of alpha-synuclein in human astrocytes,
      cortical neurons and fibroblasts.
AB  - The accumulation and aggregation of alpha-synuclein (alpha-syn) in several tissue
      including the brain is a major pathological hallmark in Parkinson's disease (PD).
      In this study, we show that alpha-syn can be taken up by primary human cortical
      neurons, astrocytes and skin-derived fibroblasts in vitro. Our findings that
      brain and peripheral cells exposed to alpha-syn can lead to impaired
      mitochondrial function, leading to cellular degeneration and cell death, provides
      additional evidence for the involvement of mitochondrial dysfunction as a
      mechanism of toxicity of alpha-syn in human cells. 

PMID- 24093919
TI  - Anti-angiotensin converting enzyme (ACE) proteins from mycelia of Ganoderma
      lucidum (Curtis) P. Karst.
AB  - BACKGROUND: Ganoderma lucidum has been purported as a potent remedy in the
      treatment and prevention of several ailments, including hypertension. This study
      aimed to explore the anti-ACE potential of protein fractions from the mycelia of
      G. lucidum. METHODS: Ganoderma lucidum mycelia were cultivated by submerged
      fermentation in a liquid medium containing brown sugar and spent brewer's yeast.
      Intracellular proteins were fractionated from mycelia crude water extract by
      ammonium sulphate precipitation, and their angiotensin converting enzyme
      inhibitory activity was evaluated. The potential anti-ACE protein fractions were
      further separated by RP-HPLC and characterised using proteomics platforms.
      RESULTS: Preliminary result demonstrated that the mycelia crude water extract
      inhibited ACE at IC50 value of 1.134 +/- 0.036 mg/mL. Following protein
      fractionation and HPLC purification, the presence of highly potential anti-ACE
      proteins with the IC50 values less than 200 MUg/mL was detected. Characterisation
      of these proteins demonstrated the presence of four different antihypertensive
      related proteins involved in the regulation of blood pressure through different
      mechanisms. CONCLUSIONS: This study suggests that the mycelia of G. lucidum has
      high potential in lowering blood pressure level due to the presence of several
      antihypertensive-related proteins such as cystathionine beta synthase-like
      protein, DEAD/DEAH box helicase-like protein, paxillin-like protein, and
      alpha/beta hydrolase-like protein.

PMID- 24093920
TI  - Competition between pyrimorph-sensitive and pyrimorph-resistant isolates of
      Phytophthora capsici.
AB  - Phytophthora capsici causes significant losses to vegetable production worldwide.
      Pyrimorph, a new carboxylic acid amide fungicide, has been registered to control
      P. capsici in China. A mutation (Q1077K) in cellulose synthase 3 has been
      reported to confer resistance to pyrimorph. In this study, we measured the
      competition between pyrimorph-resistant and pyrimorph-sensitive isolates of P.
      capsici. Mixed zoospore suspensions of resistant (R) and sensitive (S) isolates
      at five ratios (1R:9S, 3R:7S, 5R:5S, 7R:3S, and 9R:1S) were applied to carrot
      agar in vitro test (with five successive transfers) and to the soil surface
      around pepper plants in planta test (with 10 successive disease cycles). The
      proportion of resistant isolates was measured by a conventional assay in which
      single zoospore isolates recovered after transfers or disease cycles were grown
      on agar medium with a discriminatory concentration of pyrimorph. The results were
      then compared with those of a real-time polymerase chain reaction (PCR)-based
      method developed here, the results were similar. Both assays showed that the
      competitive ability of the resistant isolates was similar to or less than that of
      the sensitive isolates. The real-time PCR assay developed will be useful for high
      throughput analysis and monitoring the development of pyrimorph resistance in
      field populations of P. capsici.

PMID- 24093921
TI  - Induction of Rhizopus oryzae germination under starvation using host metabolites
      increases spore susceptibility to heat stress.
AB  - Sweetpotato is a nutritional source worldwide. Soft rot caused by Rhizopus spp.
      is a major limiting factor in the storage of produce, rendering it potentially
      unsafe for human consumption. In this study, Rhizopus oryzae was used to develop
      a concept of postharvest disease control by weakening the pathogen through
      induction of spore germination under starvation conditions. We isolated the
      sweetpotato active fractions (SPAFs) that induce spore germination and used them
      at a low dose to enhance spore weakening caused by starvation. Germination in
      SPAF at 1 mg/ml weakened the pathogen spores by delaying their ability to form
      colonies on rich media and by increasing their sensitivity to heat stress. The
      weakening effect was also supported by reduced metabolic activity, as detected by
      Alarmar Blue fluorescent dye assays. Spores incubated with SPAF at 1 mg/ml showed
      DNA fragmentation in some of their nuclei, as observed by TUNEL assay. In
      addition, these spores exhibited changes in ultrastructural morphology (i.e.,
      shrinkage of germ tubes, nucleus deformation, and vacuole formation) which are
      hallmarks of programmed cell death. We suggest that induction of spore
      germination under starvation conditions increases their susceptibility to stress
      and, therefore, might be considered a new strategy for pathogen control.

PMID- 24093922
TI  - Population Structures of 'Candidatus Liberibacter asiaticus' in Southern China.
AB  - Huanglongbing (HLB) is a highly detrimental citrus disease associated with
      'Candidatus Liberibacter asiaticus', a nonculturable alpha-proteobacterium.
      Characterization of the bacterial populations is important for development of
      disease management strategies. In this study, the 'Ca. L. asiaticus' populations
      in eight provinces in southern China where HLB is endemic were analyzed based on
      tandem repeat number (TRN) variations in a previously characterized genomic locus
      CLIBASIA_01645. Of the 224 HLB samples collected, 175 (78.3%) samples yielded
      single polymerase chain reaction (PCR) amplicons (the single amplicon group, SAG)
      and 49 (21.7%) samples produced multiple PCR amplicons (the multiple amplicon
      group, MAG). Variations in SAG are summarized by Nei's diversity index (H) and
      ratio of TRN <= 10/TRN > 10 genotypes (R10). Variations in the MAG are described
      by the percentage of occurrence (PMAG). At an orchard-level comparison, the 'Ca.
      L. asiaticus' population from a Guangdong orchard (n = 24) showed H = 0.50, R10 =
      23, and PMAG = 0, significantly different from that of the non-Guangdong orchards
      in Yunnan (n = 23), H = 0.83, R10 = 2.3, and PMAG = 11.5, and in Hainan (n = 35),
      H = 0.88, R10 = 1.5, and PMAG = 16.7. In a region-level consideration, the
      Guangdong 'Ca. L. asiaticus' population (n = 78) was H = 0.77, R10 = 25, and PMAG
      = 1.3, whereas the non-Guangdong population (n = 84) was H = 0.91, R10 = 1.6, and
      PMAG = 26.9. Overall, significant differences were observed between the 'Ca. L.
      asiaticus' population from Guangdong Province and those from the other provinces.
      A strong aggregation of TRN = 6, 7, and 8 genotypes is characteristic to the 'Ca.
      L. asiaticus' population in Guangdong. Referenced to genome annotation, we
      propose that rearrangement of tandem repeats at locus CLIBASIA_01645 could be
      associated with bacterial environmental adaptation.

PMID- 24093923
TI  - Exploitation of FTA cartridges for the sampling, long-term storage, and DNA-based
      analyses of plant-parasitic nematodes.
AB  - The use of DNA-based analyses in molecular plant nematology research has
      dramatically increased over recent decades. Therefore, the development and
      adaptation of simple, robust, and cost-effective DNA purification procedures are
      required to address these contemporary challenges. The solid-phase-based approach
      developed by Flinders Technology Associates (FTA) has been shown to be a powerful
      technology for the preparation of DNA from different biological materials,
      including blood, saliva, plant tissues, and various human and plant microbial
      pathogens. In this work, we demonstrate, for the first time, that this FTA-based
      technology is a valuable, low-cost, and time-saving approach for the sampling,
      long-term archiving, and molecular analysis of plant-parasitic nematodes. Despite
      the complex structure and anatomical organization of the multicellular bodies of
      nematodes, we report the successful and reliable DNA-based analysis of nematode
      high-copy and low-copy genes using the FTA technology. This was achieved by
      applying nematodes to the FTA cards either in the form of a suspension of
      individuals, as intact or pestle-crushed nematodes, or by the direct mechanical
      printing of nematode-infested plant tissues. We further demonstrate that the FTA
      method is also suitable for the so-called "one-nematode-assay", in which the
      target DNA is typically analyzed from a single individual nematode. More
      surprisingly, a time-course experiment showed that nematode DNA can be detected
      specifically in the FTA-captured samples many years after initial sampling
      occurs. Collectively, our data clearly demonstrate the applicability and the
      robustness of this FTA-based approach for molecular research and diagnostics
      concerning phytonematodes; this research includes economically important species
      such as the stem nematode (Ditylenchus dipsaci), the sugar beet nematode
      (Heterodera schachtii), and the Northern root-knot nematode (Meloidogyne hapla).

PMID- 24093924
TI  - Collaborators, not competitors: peer workers and professionals.

PMID- 24093925
TI  - Depression and clostridium difficile infection.

PMID- 24093928
TI  - FDA-approved drugs to treat sleep disorders.

PMID- 24093931
TI  - Perceived stigma reductions following participation in mental health services
      integrated within community-based HIV primary care.
AB  - HIV stigma remains a significant challenge for individuals living with HIV
      disease that can adversely affect overall well-being and patterns of HIV health
      service engagement. Finding ways to effectively address stigma concerns is,
      therefore, an important consideration in the clinical management of HIV disease.
      This study examined changes in perceived stigma in a sample of 48 adults living
      with HIV disease as an outcome of their participation in a mental health services
      program integrated with community-based HIV primary care. Participants completed
      a self-report instrument that provided a multidimensional measure of perceived
      HIV stigma, including distancing, blaming, and discrimination dimensions. This
      scale was administered at the baseline mental health service visit and then re
      administered at the three-month follow-up point. Study results showed reductions
      in self-reported perceived HIV stigma over time for the distancing (t = 4.01, p =
      0.000, d = 0.43), blaming (t = 2.79, p = 0.008, d = 0.35), and discrimination (t
      = 2.90, p = 0.006, d = 0.42) dimensions of stigma. These findings suggest that
      participation in HIV mental health services may have a favorable impact on
      perceived HIV stigma. Implications of these findings are discussed, including
      possible mechanisms that might explain the observed results as well as suggested
      directions for future research in this area. Randomized controlled trials would
      represent an important next step to investigate the extent to which HIV mental
      health services can reduce levels of perceived HIV stigma. 

PMID- 24093933
TI  - Improved synthesis of mono- and disubstituted 2-halonicotinonitriles from
      alkylidene malononitriles.
AB  - Pyridines with 2,3,4 and/or 5 substitution remain challenging to prepare.
      Existing strategies to form multisubstituted 2-halonicotinonitriles via enamines
      suffer from dimerization of the starting alkylidene malononitriles resulting in
      low yields. Through alteration of reaction conditions, a new high yielding method
      into enamines was realized by condensing DMF-DMA and alkylidene malononitriles in
      the presence of substoichiometric acetic anhydride. Cyclization of the resulting
      enamines under Pinner conditions provided 2-halonicotinonitriles in high overall
      yields. 

PMID- 24093934
TI  - Laparoscopic central pancreatectomy with pancreaticojejunostomy: preliminary
      experience with 8 cases.
AB  - BACKGROUND: Central pancreatectomy has been accepted as an alternative procedure
      for treating benign or low-grade malignant tumors in the pancreatic neck or
      proximal body of the pancreas, which preserves pancreatic parenchyma and
      function. In this study, we present our experience of laparoscopic central
      pancreatectomy with pancreaticojejunostomy. PATIENTS AND METHODS: From April 2011
      to February 2013, 8 patients underwent laparoscopic central pancreatectomy with a
      Roux-en-Y modified "dunking" or duct-to-mucosa pancreaticojejunostomy for benign
      or low-grade malignant tumors in the pancreatic neck or proximal body of the
      pancreas at the Department of General Surgery, Sir Run Run Shaw Hospital,
      Hangzhou, China. Surgical procedure, postoperative course, and follow-up data
      were collected. RESULTS: Laparoscopic central pancreatectomy was performed
      successfully in all the patients. The pancreaticojejunostomy was executed with a
      modified "dunking" pancreaticojejunostomy (n=7) or duct-to-mucosa
      pancreaticojejunostomy (n=1). The mean operative time was 286+/-27 minutes
      (range, 250-330 minutes), with a mean blood loss of 57+/-21 mL (range, 30-100
      mL). Mortality was 0%, and perioperative morbidity was 37.5% (pancreatic fistula
      [grade A], bleeding of a splenic vein branch, and retroperitoneal infection). The
      median postoperative hospital stay was 10 days (range, 6-38 days). At a median
      follow-up of 7.5 months (range, 2-24 months), all patients were alive without any
      exocrine or endocrine insufficiency or recurrence. CONCLUSIONS: Laparoscopic
      central pancreatectomy is feasible and safe. The modified "dunking"
      pancreaticojejunostomy can be performed safely in this approach.

PMID- 24093935
TI  - Lower extremity venous Doppler evaluation in patients undergoing laparoscopic
      gynecological operations.
AB  - BACKGROUND: Laparoscopy is established as a standard of care in a variety of
      gynecological pathologies. Pneumoperitoneum and reverse Trendelenburg positioning
      during laparoscopy have been claimed to increase thrombosis risk, albeit these
      proposals are still controversial. The aim of this study was to assess lower
      extremity venous blood flow by Doppler sonography in patients undergoing
      laparoscopic gynecological surgeries. PATIENTS AND METHODS: A prospective,
      nonrandomized, controlled study was designed to compare lower extremity venous
      Doppler measurements in patients undergoing diagnostic and operative
      gynecological laparoscopies. In the period from May 2010 to April 2011, in total,
      96 patients operated on for various gynecological complaints excluding malignancy
      were enrolled in the study. Thirty-two of these patients underwent diagnostic
      laparoscopy, 34 underwent operative laparoscopy, and 30 underwent open surgery.
      Lower extremity venous blood flow was investigated by Doppler sonography in
      patients the day before surgery and 24 hours afterward. Preoperative and
      postoperative Doppler measurements were obtained from bilateral common and
      superficial femoral, bilateral great saphenous, and bilateral popliteal veins.
      RESULTS: Lower extremity venous Doppler measurements were similar in diagnostic
      and operative laparoscopy groups. Femoral venous blood flow measurements were
      observed to be similar, but great saphenous and popliteal blood flows were found
      to be significantly decreased in the open surgery group compared with
      laparoscopic operations. CONCLUSIONS: The laparoscopic approach in gynecological
      surgery is not associated with an adverse effect on lower extremity blood flow
      and seems not to bring an additional risk of thrombosis.

PMID- 24093932
TI  - Overcoming nonviral gene delivery barriers: perspective and future.
AB  - A key end goal of gene delivery research is to develop clinically relevant
      vectors that can be used to combat elusive diseases such as AIDS. Despite
      promising engineering strategies, efficiency and ultimately gene modulation
      efficacy of nonviral vectors have been hindered by numerous in vitro and in vivo
      barriers that have resulted in subviral performance. In this perspective, we
      concentrate on the gene delivery barriers associated with the two most common
      classes of nonviral vectors, cationic-based lipids and polymers. We present the
      existing delivery barriers and summarize current vector-specific strategies to
      overcome said barriers. 

PMID- 24093937
TI  - Are ABCB1 (P-glycoprotein) polymorphisms clinically relevant in ovarian cancer? -
      Finally an Answer!

PMID- 24093936
TI  - Changes in diet and physical activity resulting from the Shape Up Somerville
      community intervention.
AB  - BACKGROUND: The purpose of this study is to describe the behavioral changes in
      children resulting from Shape Up Somerville (SUS), a community-based,
      participatory obesity prevention intervention that used a multi-level, systems
      based approach. It was set in Somerville, an urban, culturally diverse community
      in Massachusetts, USA. METHODS: This was a non-randomized, controlled 2-year
      community-based intervention trial with children enrolled in grades 1 to 3 (ages
      6-8 years). Overall, the SUS intervention was designed to create environmental
      and policy change to impact all aspects of a child's day. Pre-post outcomes were
      compared between Somerville and two control communities that were chosen based on
      socio-demographic similarities. Behavioral outcomes were fruit and vegetable and
      sugar-sweetened beverage consumption; number of organized sports and physical
      activities per year; walking to and from school; screen and television time;
      television in bedroom; and dinner in room with television on. These measures were
      assessed by parent/caregiver report using a 68-item Family Survey Form. Data were
      analyzed using multiple linear regression, accounting for covariates and
      clustering by community. RESULTS: Intervention group children, compared to the
      control group, significantly reduced sugar-sweetened beverage consumption (-2.0
      ounces per day; 95% CI -3.8 to -0.2), increased participation in organized sports
      and physical activities (0.20 sports or activities per year; 95% CI 0.06 to
      0.33), and reduced their screen time (-0.24 hours per day; 95% CI -0.42 to 
      0.06). CONCLUSIONS: Results of this study, particularly intake of sugar-sweetened
      beverages and screen time, are similar to others that used a multi-level approach
      to realize change in behavior. These results support the efficacy of a multi
      level and systems-based approach for promoting the behavioral changes necessary
      for childhood obesity prevention. This study is registered at ClinicalTrials.gov
      as NCT00153322.

PMID- 24093938
TI  - Embracing change: the key to revolutionizing SGO's future. The 2013 Society of
      Gynecologic Oncology Presidential Address. Sunday, March 10, 2013. By Ronald D.
      Alvarez, MD. 2012-2013 SGO President.

PMID- 24093939
TI  - The stress protein/chaperone Grp94 counteracts muscle disuse atrophy by
      stabilizing subsarcolemmal neuronal nitric oxide synthase.
AB  - AIMS: Redox and growth-factor imbalance fosters muscle disuse atrophy. Since the
      endoplasmic-reticulum chaperone Grp94 is required for folding insulin-like growth
      factors (IGFs) and for antioxidant cytoprotection, we investigated its
      involvement in muscle mass loss due to inactivity. RESULTS: Rat soleus muscles
      were transfected in vivo and analyzed after 7 days of hindlimb unloading, an
      experimental model of muscle disuse atrophy, or standard caging. Increased muscle
      protein carbonylation and decreased Grp94 protein levels (p<0.05) characterized
      atrophic unloaded solei. Recombinant Grp94 expression significantly reduced
      atrophy of transfected myofibers, compared with untransfected and empty-vector
      transfected ones (p<0.01), and decreased the percentage of carbonylated myofibers
      (p=0.001). Conversely, expression of two different N-terminal deleted Grp94
      species did not attenuate myofiber atrophy. No change in myofiber trophism was
      detected in transfected ambulatory solei. The absence of effects on atrophic
      untransfected myofibers excluded a major role for IGFs folded by recombinant
      Grp94. Immunoprecipitation and confocal microscopy assays to investigate
      chaperone interaction with muscle atrophy regulators identified 160 kDa neuronal
      nitric oxide synthase (nNOS) as a new Grp94 partner. Unloading was demonstrated
      to untether nNOS from myofiber subsarcolemma; here, we show that such nNOS
      localization, revealed by means of NADPH-diaphorase histochemistry, appeared
      preserved in unloaded myofibers expressing recombinant Grp94, compared to those
      transfected with the empty vector or deleted Grp94 cDNA (p<0.02). INNOVATION:
      Grp94 interacts with nNOS and prevents its untethering from sarcolemma in
      unloaded myofibers. CONCLUSION: Maintenance of Grp94 expression is sufficient to
      counter unloading atrophy and oxidative stress by mechanistically stabilizing
      nNOS-multiprotein complex at the myofiber sarcolemma.

PMID- 24093940
TI  - Optimization of benzodiazepinones as selective inhibitors of the X-linked
      inhibitor of apoptosis protein (XIAP) second baculovirus IAP repeat (BIR2)
      domain.
AB  - The IAPs are key regulators of the apoptotic pathways and are commonly
      overexpressed in many cancer cells. IAPs contain one to three BIR domains that
      are crucial for their inhibitory function. The pro-survival properties of XIAP
      come from binding of the BIR domains to the pro-apoptotic caspases. The BIR3
      domain of XIAP binds and inhibits caspase 9, while the BIR2 domain binds and
      inhibits the terminal caspases 3 and 7. While XIAP BIR3 inhibitors have
      previously been reported, they also inhibit cIAP1/2 and promote the release of
      TNFalpha, potentially limiting their therapeutic utility. This paper will focus
      on the optimization of selective XIAP BIR2 inhibitors leading to the discovery of
      highly potent benzodiazepinone 36 (IC50 = 45 nM), which has high levels of
      selectivity over XIAP BIR3 and cIAP1 BIR2/3 and shows efficacy in a xenograft
      pharmacodynamic model monitoring caspase activity while not promoting the release
      of TNFalpha in vitro. 

PMID- 24093944
TI  - Comparative analysis of proteomic profiles between endometrial caruncular and
      intercaruncular areas in ewes during the peri-implantation period.
AB  - The endometrium of sheep consists of plenty of raised aglandular areas called
      caruncular (C), and intensely glandular intercaruncular areas (IC). In order to
      better understand the endometrium involved mechanisms of implantation, we used LC
      MS/MS technique to profile the proteome of ovine endometrial C areas and IC areas
      separately during the peri-implantation period, and then compared the proteomic
      profiles between these two areas. We successfully detected 1740 and 1813 proteins
      in C areas and IC areas respectively. By comparing the proteome of these two
      areas, we found 170 differentially expressed proteins (DEPs) (P < 0.05),
      functional bioinformatics analysis showed these DEPs were mainly involved in
      growth and remodeling of endometrial tissue, cell adhesion and protein transport,
      and so on. Our study, for the first time, provided a proteomic reference for
      elucidating the differences between C and IC areas, as an integrated function
      unit respectively, during the peri-implantation period. The results could help us
      to better understand the implantation in the ewes. In addition, we established a
      relatively detailed protein database of ovine endometrium, which provide a unique
      reference for further studies. 

PMID- 24093946
TI  - Multiorder correction algorithms to remove image distortions from mass
      spectrometry imaging data sets.
AB  - Time-of-flight secondary ion mass spectrometry imaging is a rapidly evolving
      technology. Its main application is the study of the distribution of small
      molecules on biological tissues. The sequential image acquisition process remains
      susceptible to measurement distortions that can render imaging data less
      analytically useful. Most of these artifacts show a repetitive nature from tile
      to tile. Here we statistically describe these distortions and derive two
      different algorithms to correct them. Both a generalized linear model approach
      and the linear discriminant analysis approach are able to increase image quality
      for negative and positive ion mode data sets. Additionally, performing simulation
      studies with repetitive and nonrepetitive tiling error we show that both
      algorithms are only removing repetitive distortions. It is further shown that the
      spectral component of the data set is not altered by the use of these correction
      methods. Both algorithms presented in this work greatly increase the image
      quality and improve the analytical usefulness of distorted images dramatically. 

PMID- 24093945
TI  - Chemiluminescent detection of enzymatically produced hydrogen sulfide: substrate
      hydrogen bonding influences selectivity for H2S over biological thiols.
AB  - Hydrogen sulfide (H2S) is now recognized as an important biological regulator and
      signaling agent that is active in many physiological processes and diseases.
      Understanding the important roles of this emerging signaling molecule has
      remained challenging, in part due to the limited methods available for detecting
      endogenous H2S. Here we report two reaction-based ChemiLuminescent Sulfide
      Sensors, CLSS-1 and CLSS-2, with strong luminescence responses toward H2S (128-
      and 48-fold, respectively) and H2S detection limits (0.7 +/- 0.3, 4.6 +/- 2.0
      MUM, respectively) compatible with biological H2S levels. CLSS-2 is highly
      selective for H2S over other reactive sulfur, nitrogen, and oxygen species
      (RSONS) including GSH, Cys, Hcy, S2O3(2-), NO2(-), HNO, ONOO(-), and NO. Despite
      its similar chemical structure, CLSS-1 displays lower selectivity toward amino
      acid-derived thiols than CLSS-2. The origin of this differential selectivity was
      investigated using both computational DFT studies and NMR experiments. Our
      results suggest a model in which amino acid binding to the hydrazide moiety of
      the luminol-derived probes provides differential access to the reactive azide in
      CLSS-1 and CLSS-2, thus eroding the selectivity of CLSS-1 for H2S over Cys and
      GSH. On the basis of its high selectivity for H2S, we used CLSS-2 to detect
      enzymatically produced H2S from isolated cystathionine gamma-lyase (CSE) enzymes
      (p < 0.001) and also from C6 cells expressing CSE (p < 0.001). CLSS-2 can readily
      differentiate between H2S production in active CSE and CSE inhibited with beta
      cyanoalanine (BCA) in both isolated CSE enzymes (p < 0.005) and in C6 cells (p <
      0.005). In addition to providing a highly sensitive and selective reaction-based
      tool for chemiluminescent H2S detection and quantification, the insights into
      substrate-probe interactions controlling the selectivity for H2S over
      biologically relevant thiols may guide the design of other selective H2S
      detection scaffolds.

PMID- 24093947
TI  - Elevated hydrogen peroxide and decreased catalase and glutathione peroxidase
      protection are associated with aging sarcopenia.
AB  - BACKGROUND: Sarcopenia is the progressive loss of skeletal muscle that
      contributes to the decline in physical function during aging. A higher level of
      oxidative stress has been implicated in aging sarcopenia. The current study aims
      to determine if the higher level of oxidative stress is a result of increased
      superoxide (O2?) production by the NADPH oxidase (NOX) enzyme or decrease in
      endogenous antioxidant enzyme protection. METHODS: Female Balb/c mice were
      assigned to 4 age groups; 6, 12, 18 and 24 months. Body weight and animal
      survival rates were recorded over the course of the study. Skeletal muscle
      tissues were collected and used to measure NOX subunit mRNA, O2? levels and
      antioxidant enzymes. RESULTS: Key subunit components of NOX expression were
      elevated in skeletal muscle at 18 months, when sarcopenia was first evident.
      Increased superoxide dismutase 1 (SOD1) activity suggests an increase in O2?
      dismutation and this was further supported by elevated levels of hydrogen
      peroxide (H2O2) and decline in catalase and glutathione peroxidase (GPx)
      antioxidant protection in skeletal muscle at this time. NOX expression was also
      higher in skeletal muscle at 24 months, however this was coupled with elevated
      levels of O2? and a decline in SOD1 activity, compared to 6 and 12 months but was
      not associated with further loss of muscle mass. CONCLUSIONS: While the source of
      ROS in sarcopenic muscle remains unknown, this study provides evidence that the
      NOX enzyme could be involved in ROS production by regulating superoxide in ageing
      muscles. This study also suggests that H2O2 is the key ROS in the onset of
      sarcopenia and that the decline in antioxidant protection by catalase and GPx is
      indicative of antioxidant dysfunction and may therefore be a major contributing
      factor in the development or onset of sarcopenia. Furthermore, the changes in ROS
      and antioxidant activity after sarcopenia was first evident gives some evidence
      for a compensatory mechanism, in response to insult, in order to maintain muscle
      integrity.

PMID- 24093952
TI  - Regional conferences--a capacity-building mandate: report on CRCP2011-Building
      Bridges and Building a Regional Structure.
AB  - The Caribbean Regional Conference of Psychology was held in Nassau, The Bahamas,
      from 15 to 18 November 2011, under the auspices of the International Association
      of Applied Psychology (IAAP), the International Union of Psychological Science
      (IUPsyS), and the International Association for Cross-Cultural Psychology
      (IACCP). The conference was hosted by the Bahamas Psychological Association, and
      organized by a committee chaired by Dr Ava Thompson, College of the Bahamas. The
      CRCP2011 attracted over 400 participants from 37 countries, including 20
      nations/territories in the Caribbean. A broad scientific program, organized
      around six conference themes, addressed strengths and challenges to psychology in
      the region; the current state of psychological research, assessment, and
      intervention; historical, cultural, and language influences; and links between
      Caribbean and global models. Conference outcomes included planning for a series
      of publications to expand on conference themes and presentations, as well as
      establishment of a steering group to launch a regional organization to support
      the science and practice of psychology in the Caribbean. 

PMID- 24093951
TI  - Increasing trends in primary NNRTI resistance among newly HIV-1-diagnosed
      individuals in Buenos Aires, Argentina.
AB  - OBJECTIVE: Our objective was to estimate primary resistance in an urban setting
      in a developing country characterized by high antiretroviral (ARV) coverage over
      the diagnosed population and also by an important proportion of undiagnosed
      individuals, in order to determine whether any change in primary resistance
      occurred in the past five years. DESIGN: We carried out a multi-site resistance
      surveillance study according to WHO HIV resistance guidelines, using a weighted
      sampling technique based on annual HIV case reports per site. METHODS: Blood
      samples were collected from 197 drug-naive HIV-1-infected individuals diagnosed
      between March 2010 and August 2011 at 20 HIV voluntary counselling and testing
      centres in Buenos Aires. Clinical records of enrolled patients at the time of
      diagnosis were compiled. Viral load and CD4 counts were performed on all samples.
      The pol gene was sequenced and the resistance profile determined. Phylogenetic
      analysis was performed by neighbour-joining (NJ) trees and bootscanning analysis.
      RESULTS: We found that 12 (7.9%) of the 152 successfully sequenced samples
      harboured primary resistance mutations, of which K103N and G190A were the most
      prevalent. Non-nucleoside reverse transcriptase inhibitors (NNRTI) resistance
      mutations were largely the most prevalent (5.9%), accounting for 75% of all
      primary resistance and exhibiting a significant increase (p=0.0072) in prevalence
      during the past 10 years as compared to our previous study performed in 1997-2000
      and in 2003-2005. Nucleoside reverse transcriptase inhibitor (NRTI) and protease
      inhibitor primary resistance were low and similar to the one previously reported.
      CONCLUSIONS: Levels of primary NNRTI resistance in Buenos Aires appear to be
      increasing in the context of a sustained ARV coverage and a high proportion of
      undiagnosed HIV-positive individuals.

PMID- 24093953
TI  - Cancer vaccines: looking to the future. Interview by Jenaid Rees.
AB  - Interview by Jenaid Rees (Commissioning Editor) Vasso Apostolopoulos has been
      working in the field of cancer vaccines since 1991, and human clinical trials on
      her work have been conducted since 1994. Her work has been at the forefront of
      scientific research into the development of a vaccine for cancer and she has
      received over 90 awards and honours in recognition of her achievements. Some
      notable awards include, the Premier's Award for medical research, was named Young
      Australian of the Year (Victoria), recipient of the Channel 10/Herald Sun Young
      Achiever of the Year Award as well as being awarded the Order of Brigadier
      General of the Phoenix Battalion by the Greek President. In 1998 Apostolopoulos
      received the NHMRC CJ Martin Research Fellowship and worked at the Scripps
      Research Institute in California, USA, for 3.5 years and returned to the Austin
      Research Institute (VIC, Australia), and headed the Immunology and Vaccine
      Laboratory receiving the NHMRC RD Wright Fellowship. Upon her return to
      Australia, Apostolopoulos received the Victorian Tall Poppy Award, the Bodossaki
      Foundation Academic Prize, was inducted into the Victorian Honour roll of Women,
      was a torchbearer for the Melbourne leg of the International Athens 2004 Olympic
      Torch Relay, was named Woman of the Year, and is an Australia Day Ambassador. Her
      contribution into cancer research, vaccines and immunology has been extensive -
      publishing over 200 scientific papers and books, an inventor on 14 patents and
      collaborates with over 50 national and international Research Institutes and
      Universities. Her current research interests are in the development of new
      improved cancer vaccines and new modes of antigen delivery for immune
      stimulation. She is also interested in chronic diseases treatment and prevention
      through immunotherapy. She serves on the Editorial Board for Expert Review of
      Vaccines. 

PMID- 24093950
TI  - Standard versus accelerated initiation of renal replacement therapy in acute
      kidney injury (STARRT-AKI): study protocol for a randomized controlled trial.
AB  - BACKGROUND: Acute kidney injury is a common and devastating complication of
      critical illness, for which renal replacement therapy is frequently needed to
      manage severe cases. While a recent systematic review suggested that "earlier"
      initiation of renal replacement therapy improves survival, completed trials are
      limited due to small size, single-centre status, and use of variable definitions
      to define "early" renal replacement therapy initiation. METHODS/DESIGN: This is
      an open-label pilot randomized controlled trial. One hundred critically ill
      patients with severe acute kidney injury will be randomly allocated 1:1 to
      receive "accelerated" initiation of renal replacement therapy or "standard"
      initiation at 12 centers across Canada. In the accelerated arm, participants will
      have a venous catheter placed and renal replacement therapy will be initiated
      within 12 hours of fulfilling eligibility. In the standard initiation arm,
      participants will be monitored over 7 days to identify indications for renal
      replacement therapy. For participants in the standard arm with persistent acute
      kidney injury, defined as a serum creatinine not declining >50% from the value at
      the time of eligibility, the initiation of RRT will be discouraged unless one or
      more of the following criteria are fulfilled: serum potassium >=6.0 mmol/L; serum
      bicarbonate <=10 mmol/L; severe respiratory failure (PaO2/FiO2<200) or persisting
      acute kidney injury for >=72 hours after fulfilling eligibility. The inclusion
      criteria are designed to identify a population of critically ill adults with
      severe acute kidney injury who are likely to need renal replacement therapy
      during their hospitalization, but not immediately. The primary outcome is
      protocol adherence (>90%). Secondary outcomes include measures of feasibility
      (proportion of eligible patients enrolled in the trial, proportion of enrolled
      patients followed to 90 days for assessment of vital status and the need for
      renal replacement therapy) and safety (occurrence of adverse events). DISCUSSION:
      The optimal timing of renal replacement therapy initiation in patients with
      severe acute kidney injury remains uncertain, representing an important knowledge
      gap and a priority for high-quality research. This pilot trial is necessary to
      establish protocol feasibility, confirm the safety of participants and obtain
      estimated events rates for design of a large definitive trial. TRIAL REGISTRATION
      NUMBER: NCT01557361.

PMID- 24093954
TI  - Meditation-based interventions for family caregivers of people with dementia: a
      review of the empirical literature.
AB  - OBJECTIVES: Providing care for a family member with dementia is associated with
      increased risk of adverse mental health sequelae. Recently, interventions
      utilising meditation-based techniques have been developed with the aim of
      reducing psychological distress among dementia caregivers. The present review
      aimed to critically evaluate the extant empirical literature in order to
      determine: (1) whether meditation-based interventions can reduce depression among
      dementia caregivers and (2) whether meditation-based interventions can reduce
      subjective burden among dementia caregivers. METHOD: After adhering to inclusion
      and exclusion criteria, a total of eight studies were included in the present
      review. Methodological quality was assessed using one of two scales dependent on
      study design. RESULTS: The results provide tentative evidence that meditation
      based interventions do indeed improve levels of depression and burden in family
      dementia caregivers. CONCLUSIONS: The review highlighted the strengths and
      weakness of the studies' methodological designs. Whilst this novel review offers
      evidence in support of meditation-based interventions to improve the
      psychological distress of family dementia caregivers, future research should
      direct efforts to conduct larger scale, more rigorous studies. Clinical
      implications of the findings are also discussed.

PMID- 24093955
TI  - The link between information and communication technologies and global public
      health: pushing forward.
AB  - .Global public health (GPH) continues to be a challenging field. It focuses on
      health-related issues that transcend national boundaries and thus requires global
      cooperation for implementing solutions to public health problems. Information and
      communication technologies (ICTs) have the potential to contribute to GPH by
      improving the quality of healthcare services. The purpose of this commentary
      article is to discuss the nature and characteristics of the existing link between
      ICTs and GPH. The key underlying questions discussed in this article are (a)
      whether ICTs can truly reduce the burden of current GPH problems and (b) how to
      effectively achieve it. We selected three widely recognized GPH challenges:
      diarrheal disease among children under 5 years old, malaria, and type 2 diabetes
      mellitus. These are considered to be examples of salient global issues that,
      despite the availability of cost-effective preventive and therapeutic
      interventions, still remain a major burden of morbidity and mortality worldwide.
      We conclude that there is a growing global interest in ICT-related solutions in
      GPH. We recommend the development of more transparent frameworks, more theory
      informed solutions, and clearer translational links between ICTs and GPH matters.
      Ten further specific recommendations are also discussed in this article.

PMID- 24093957
TI  - Depression and suicidality during the postpartum period after first time
      deliveries, active component service women and dependent spouses, U.S. Armed
      Forces, 2007-2012.
AB  - Although suicide is a leading cause of death among new mothers during the
      postpartum period, there has been limited research on self-harm in the postpartum
      period and associated risk factors. One potential risk factor for suicidality
      (completed suicides, suicide attempts, and suicide ideation including thoughts of
      self harm) during the postpartum period is postpartum depression (PPD). In this
      study of women who gave birth for the first time between 1 January 2007 and 31
      December 2011, 5,267 (9.9% of all who delivered) active component service women
      and 10,301 (8.2%) dependent spouses received incident PPD diagnoses during the
      one year postpartum period; 213 (0.4%) service women and 221 (0.2%) dependent
      spouses were diagnosed with incident suicidality. After adjusting for the effects
      of other covariates, service women with PPD had 42.2 times the odds to be
      diagnosed with suicidality in the postpartum period compared to service women
      without PPD; dependent spouses with PPD had 14.5 times the odds compared to those
      without PPD. The findings of this report suggest that a history of mental
      disorders was common among service women and dependent spouses with PPD in the
      postpartum period, and, in turn, PPD was a strong predictor for suicidality in
      the postpartum period. These results emphasize the importance of PPD screening
      during the postpartum period. They also suggest that additional focused screening
      for suicidal behavior among those already diagnosed with PPD may be warranted. 

PMID- 24093956
TI  - LBH589 Inhibits proliferation and metastasis of hepatocellular carcinoma via
      inhibition of gankyrin/STAT3/Akt pathway.
AB  - BACKGROUND: Gankyrin has shown to be overexpressed in human liver cancers and
      plays a complex role in hepatocarcinogenesis. Panobinostat (LBH589), a new
      hydroxamic acid-derived histone deacetylase inhibitor has shown promising
      anticancer effects recently. Here, we investigated the potential of LBH589 as a
      form of treatment for hepatocellular carcinoma (HCC). METHODS: Gankyrin plasmid
      was transfected into HCC cells, and the cells were selected for more than 4 weeks
      by incubation with G418 for overexpression clones. The therapeutic effects of
      LBH589 were evaluated in vitro and in vivo. Cell proliferation, apoptosis, cell
      cycle, invasive potential, and epithelial-mesenchy-mal transition (EMT) were
      examined. RESULTS: LBH589 significantly inhibited HCC growth and metastasis in
      vitro and in vivo. Western blotting analysis indicated that LBH589 could decrease
      the expression of gankyrin and subsequently reduced serine-phosphorylated Akt and
      tyrosine-phosphorylated STAT3 expression although the total Akt and STAT3 were
      unaffected. LBH589 inhibited metastasis in vitro via down-regulation of N
      cadherin, vimentin, TWIST1, VEGF and up-regulation of E-cadherin. LBH589 also
      induced apoptosis and G1 phase arrest in HCC cell lines. Ectopic expression of
      gankyrin attenuated the effects of LBH589, which indicates that gankyrin might
      play an important role in LBH589 mediated anticancer effects. Lastly, in vivo
      study indicated that LBH589 inhibited tumor growth and metastasis, without
      discernable adverse effects comparing to control group, with abrogating
      gankyrin/STAT3/Akt pathway. CONCLUSIONS: Our results suggested that LBH589 could
      inhibit HCC growth and metastasis through down-regulating gankyrin/STAT3/Akt
      pathway. LBH589 may present itself as a novel therapeutic strategy for HCC.

PMID- 24093958
TI  - Female infertility, active component service women, U.S. Armed Forces, 2000-2012.
AB  - Infertility is the inability to become pregnant after one year of regular,
      unprotected sexual intercourse. Among active component service women, 16,807
      received a diagnosis of female infertility during the 13-year surveillance
      period. The incidence rate of infertility diagnoses increased during the period,
      mainly due to increasing rates of infertility of unspecified origin. Infertility
      of tubal origin and anovulation were the most common specified types of
      infertility. Incidence rates of infertility were highest among women in their
      thirties; however, rates increased the most in women in their forties. Black, non
      Hispanic women had the highest rates of infertility overall and in infertility of
      tubal and uterine origin. The higher rates among women in their thirties and
      forties may reflect high and increasing rates of clinical care seeking for
      infertility among women who elect to delay pregnancy until older ages and an
      increase in treatment options for women who have been unable to become pregnant. 

PMID- 24093959
TI  - Brief report: Polycystic ovary syndrome, active component service women, U.S.
      Armed Forces, 2000-2012.

PMID- 24093960
TI  - Pelvic inflammatory disease among female recruit trainees, active component, U.S.
      Armed Forces, 2002-2012.
AB  - Pelvic inflammatory disease (PID) is a bacterial infection causing an
      inflammatory reaction in the upper genital tract. It can be treated with
      antibiotics, but since it is often asymptomatic, women often delay seeking health
      care, which may result in long-term sequelae such as infertility. Among 161,501
      female recruits who began basic training between January 2002 and December 2011,
      1,750 (1.1%) met the surveillance case definition for PID during the 12 months
      following completion of their basic military training. The overall incidence rate
      (11.2 per 1,000 person-years) showed a stable trend during the surveillance
      period, with the exception of a decline for females accessed in 2011. The
      unadjusted rates were higher among women who were not screened for chlamydia
      during basic training. Compared to their respective counterparts, rates were
      higher in service women aged 17-20, of black, non-Hispanic race/ethnicity,
      married, in the Army, and who had a chlamydia diagnosis after basic training. The
      lowest rates were among women 25 years and older, other race/ethnicity, and in
      the Coast Guard. The findings in this report may warrant further evaluation of
      the long-term impact of chlamydia screening programs for recruit trainees on PID
      and PID-related sequelae among service women. 

PMID- 24093961
TI  - Menorrhagia, active component service women, U.S. Armed Forces, 1998-2012.
AB  - Menorrhagia (excessive menstrual bleeding) is relatively common among women of
      reproductive age and may be caused by a wide range of different conditions.
      Menorrhagia symptoms can interfere with work and quality of life and may result
      in iron deficiency anemia due to chronic blood loss. This analysis of active
      component service women of the U.S. Armed Forces found that, during the
      surveillance period of 1998 through 2012, the crude incidence rate of menorrhagia
      was 6.2 cases per 1,000 person years. Annual incidence rates rose steadily
      throughout the period. Compared to their respective counterparts, rates were
      highest in women who were aged 40 to 49 or were of black, non-Hispanic ethnicity.
      Among women with menorrhagia whose records documented co-ocurring conditions, the
      most common such conditions were uterine disorders (e.g., fibroids) and ovarian
      cysts. Less than one percent of cases had underlying bleeding disorders
      documented. Of women hospitalized with the diagnosis of menorrhagia, 79 percent
      underwent hysterectomy during their hospitalizations. Limitations of the analysis
      and possible future studies are discussed. 

PMID- 24093962
TI  - Incident diagnoses of breast cancer, active component service women, U.S. Armed
      Forces, 2000-2012.
AB  - In the United States, with the exception of skin cancer, breast cancer accounts
      for the greatest number of incident cancer diagnoses in women and is the second
      most frequent cause of female cancer-related deaths. Compared to the general U.S.
      population, female military members have been estimated to have higher breast
      cancer rates. Between 2000 and 2012, 1,092 female active component members were
      diagnosed with breast cancer; 244 (22.3%) of these cases were ductal carcinoma in
      situ (DCIS). The overall crude incidence rate of breast cancer was 40.6 per
      100,000 person-years (p-yrs); the lowest annual incidence rate was 28.6 per
      100,000 p-yrs in 2006, and the highest annual incidence rate was 53.6 per 100,000
      p-yrs in 2001. Over the surveillance period, the crude incidence rate of DCIS
      cases was 9.1 per 100,000 p-yrs; for other (invasive) breast cancer diagnoses the
      rate was 31.5 per 100,000. Potential differences in breast cancer risk factors
      between military and civilian women are discussed. 

PMID- 24093963
TI  - A systematic approach identifies FOXA1 as a key factor in the loss of epithelial
      traits during the epithelial-to-mesenchymal transition in lung cancer.
AB  - BACKGROUND: The epithelial-to-mesenchymal transition is an important mechanism in
      cancer metastasis. Although transcription factors including SNAIL, SLUG, and
      TWIST1 regulate the epithelial-to-mesenchymal transition, other unknown
      transcription factors could also be involved. Identification of the full
      complement of transcription factors is essential for a more complete
      understanding of gene regulation in this process. Chromatin immunoprecipitation
      sequencing (ChIP-Seq) technologies have been used to detect genome-wide binding
      of transcription factors; here, we developed a systematic approach to integrate
      existing ChIP-Seq and transcriptome data. We scanned multiple transcription
      factors to investigate their functional impact on the epithelial-to-mesenchymal
      transition in the human A549 lung adenocarcinoma cell line. RESULTS: Among the
      transcription factors tested, impact scores identified the forkhead box protein
      A1 (FOXA1) as the most significant transcription factor in the epithelial-to
      mesenchymal transition. FOXA1 physically associates with the promoters of its
      predicted target genes. Several critical epithelial-to-mesenchymal transition
      effectors involved in cellular adhesion and cellular communication were
      identified in the regulatory network of FOXA1, including FOXA2, FGA, FGB, FGG,
      and FGL1. The implication of FOXA1 in the epithelial-to-mesenchymal transition
      via its regulatory network indicates that FOXA1 may play an important role in the
      initiation of lung cancer metastasis. CONCLUSIONS: We identified FOXA1 as a
      potentially important transcription factor and negative regulator in the initial
      stages of lung cancer metastasis. FOXA1 may modulate the epithelial-to
      mesenchymal transition via its transcriptional regulatory network. Further, this
      study demonstrates how ChIP-Seq and expression data could be integrated to
      delineate the impact of transcription factors on a specific biological process.

PMID- 24093964
TI  - Pituitary aspergillosis in a kidney transplant recipient and review of the
      literature.
AB  - Pituitary aspergillosis is a very rare disease, documented in only 12 cases.
      Although seen in both immunocompetent and immunocompromised patients, serious
      invasive sequelae, such as meningoencephalitis and death, have been noted in
      immunocompromised patients. Immunocompromised patients are susceptible and
      require complex multidisciplinary care to contain the spread of infection and
      maximize outcomes. This is the first case report, to our knowledge, of pituitary
      aspergillosis in the setting of an organ transplant. A 68-year-old woman
      presented with cephalgia, left temporal hemianopsia, and ptosis. Non-contrast
      magnetic resonance imaging of the head revealed a sellar mass, which was believed
      to be a benign pituitary adenoma. She underwent trans-sphenoidal resection, and
      subsequent histopathologic examination showed aspergillosis. She was subsequently
      started on voriconazole. On postoperative day 3, she developed a left anterior
      cerebral artery ischemic stroke, likely from Aspergillus angioinvasion and
      occlusion. Her mental status declined further and she died when care was
      withdrawn. 

PMID- 24093965
TI  - Association between tuberculin skin test result and clinical presentation of
      tuberculosis disease.
AB  - BACKGROUND: The tuberculin skin test (TST) is used to test for latent
      tuberculosis (TB) infection and support the diagnosis of active TB. However,
      little is known about the relationship between the TST result and the clinical
      presentation of TB disease. METHODS: We analyzed US TB surveillance data, 1993
      2010, and used multinomial logistic regression to calculate the association
      between TST result (0-4 mm [negative], 5-9 mm, 10-14 mm, and  >= 15 mm) and
      clinical presentation of disease (miliary, combined pulmonary and extrapulmonary,
      extrapulmonary only, non-cavitary pulmonary, and cavitary pulmonary). For persons
      with pulmonary disease, multivariate logistic regression was used to calculate
      the odds of having acid-fast bacilli (AFB) positive sputum. RESULTS: There were
      64,238 persons with culture-confirmed TB included in the analysis, which was
      stratified by HIV status and birthplace (US- vs. foreign-born). Persons with a
      TST >= 15 mm were less likely to have miliary or combined pulmonary and
      extrapulmonary disease, but more likely to have cavitary pulmonary disease than
      non-cavitary pulmonary disease. Persons with non-cavitary pulmonary disease with
      a negative TST were significantly more likely to have AFB positive sputum.
      CONCLUSIONS: Clinical presentation of TB disease differed according to TST result
      and persons with a negative TST were more likely to have disseminated disease
      (i.e., miliary or combined pulmonary and extrapulmonary). Further study of the
      TST result may improve our understanding of the host-pathogen relationship in TB
      disease.

PMID- 24093966
TI  - Can recombinant human glutathione peroxidase 1 with high activity be efficiently
      produced in Escherichia coli ?
AB  - Cellular glutathione peroxidase 1 (GPx1) is an important antioxidant
      selenoenzyme. Due to the presence of selenocysteine (Sec) encoded by UGA,
      normally recognized as a stop codon, the expression of mammalian GPx with
      traditional recombinant DNA technology is extremely difficult. In this study, a
      series of human GPx1 (hGPx1) mutants with significantly high catalytic activities
      were produced for the first time in an Escherichia coli BL21(DE3)cys auxotrophic
      strain using the single-protein production system. Cys residues in hGPx1 were
      mutated to Ser in turn because untargeted substitution of Sec in place of Cys
      resulted in the decline of recombinant selenoenzyme activity. The results of this
      work showed that the catalytic activities of the mutants increased progressively
      with decreasing number of noncatalytic Sec residues. Seleno-hGPx1
      C2/78/115/156/202S with all Cys residues changed to Ser showed the highest
      activity (21,268 U/MUmol), which was more than 10-fold higher than bovine liver
      GPx. This increase could be explained by structural analysis of hGPx1 mutants
      based on homology modeling and binding site analysis. These results lead to the
      hypothesis that the conversion of noncatalytic Sec residues to Ser may optimize
      the structure of seleno-GPx in this expression system and consequently increase
      the catalytic efficiency.

PMID- 24093967
TI  - Osteoclast differentiation inhibitors: a patent review (2008 - 2012).
AB  - INTRODUCTION: Mononuclear macrophage/monocyte-lineage hematopoietic precursors
      differentiate into multinucleated osteoclasts. Abnormally increased numbers
      and/or overactivation of osteoclasts can lead to bone loss. Therefore,
      pharmaceutical inhibition of osteoclast differentiation is one therapeutic
      strategy for mitigating the occurrence of bone loss-associated disorders and
      related fractures. AREAS COVERED: This review surveys the patents and patent
      applications from 2008 to 2012 that are related to inventions of therapeutics
      and/or methods for inhibiting osteoclast differentiation. EXPERT OPINION: Over
      the past 20 years, the identification and validation of signaling molecules
      involved in osteoclast differentiation has led to a better understanding of the
      molecular mechanism, and to the development of new therapeutic agents for
      treating bone loss-associated disorders. Since 2008, 34 WO patents or patent
      applications have been filed that relate to inventions of therapeutics and/or
      methods for chemical-based, natural product-based, or biological-based inhibitors
      of osteoclast differentiation. Here, analysis of these patents and patent
      applications is presented, and summarize the disclosed osteoclast differentiation
      inhibiting target molecules. This report can support further advances in the
      development of anti-osteoclastogenic therapeutics for bone loss-associated
      disorders, including osteoporosis, rheumatoid arthritis, Paget's disease,
      periodontal disease, osteosarcoma, and cancer bone metastasis.

PMID- 24093968
TI  - Comparison of short-term clinical outcomes between robotic and laparoscopic
      gastrectomy for gastric cancer: a meta-analysis of 2495 patients.
AB  - BACKGROUND: Laparoscopic gastrectomy (LG) is being increasingly used to treat
      gastric cancer. However, there are still several technical disadvantages limiting
      its use. Robotic gastrectomy (RG) is an emerging minimally invasive technique
      that overcomes some of these limitations. This study compares RG with LG in the
      treatment of gastric cancer by performing a systematic review and meta-analysis
      of all published literature. MATERIALS AND METHODS: Comparative studies published
      between January 1991 and April 2013 in the major databases were systematically
      searched. Evaluated end points were operative, postoperative, and oncological
      outcomes. Pooled odds ratios and weighted mean differences with 95% confidence
      intervals were calculated using either the fixed-effects model or random-effects
      model. RESULTS: Nine nonrandomized comparative studies with 2495 patients were
      included, of which 736 procedures were robotic and 1759 were laparoscopic. RG was
      associated with a lower intraoperative blood loss and a shorter time to oral
      intake compared with LG. However, it was associated with a significantly longer
      operative time and shorter distal resection margin. In addition, there was no
      significant difference in the number of retrieved lymph nodes, proximal resection
      margin, rate of conversion to open surgery, overall morbidity, anastomotic
      leakage, anastomotic stenosis, intestinal obstruction, time to first flatus,
      length of hospital stay, and perioperative mortality rates between the two
      groups. CONCLUSIONS: RG is comparable to LG, with respect to safety, technical
      feasibility, and oncological effectiveness in the treatment of gastric cancer.
      However, there is a need for well-designed prospective randomized controlled
      studies comparing the two procedures with long-term follow-up, to inform future
      practice.

PMID- 24093969
TI  - Observational study of patient and surgeon preoperative preparation in ten
      companion animal clinics in Ontario, Canada.
AB  - BACKGROUND: Surgical site infections (SSIs) are a recognized risk of any surgical
      procedure in veterinary medicine. One of the keys to prevention of SSIs is
      reducing exposure of the surgical site to endogenous and exogenous microbes,
      beginning in the preoperative period. While guidelines are available for
      preoperative preparation procedures, there has been no objective investigation of
      compliance with these recommendations in veterinary practices. The objectives of
      this pilot study were to describe preoperative patient and surgeon preparation
      practices in a sample of non-equine companion animal veterinary clinics, and to
      determine if there were any areas that consistently did not meet current
      guidelines. RESULTS: Observation of preparation practices was performed in 10
      clinics over 9-14 days each using up to 3 small wireless surveillance cameras.
      Data were coded for 148 surgical patients, and 31 surgeons performing 190
      preoperative preparations. When patient hair removal was observed, it was most
      commonly done using clippers (117/133, 88%), and in only one case was it
      performed prior to anesthetic induction. Patient contact time with soap ranged
      from 10-462 s (average of clinic means 75 s, average of clinic medians 67 s), and
      with alcohol from 3-220 s (average of clinic means 44 s, average of clinic
      medians 37 s). Alcohol-based hand rub (AHR) was used preoperatively in 2/10
      facilities, but soap-and-water hand scrub was most commonly used at all clinics.
      Proximal-to-distal scrubbing was noted in 95/142 (67%) of soap-and-water scrubs.
      Contact time during surgeon hand preparation ranged from 7-529 s (average mean
      121 s, average median 122 s) for soap-and-water and from 4-123 s (average mean 25
      s, average median 19 s) for AHR. No significant changes in practices were
      identified over time during the observation period. Practices that did not
      conform to guidelines available in major companion animal surgical textbooks were
      commonly observed. CONCLUSIONS: Some preoperative preparation practices were
      relatively consistent between clinics in this study, while others were quite
      variable. Contact times with preoperative preparatory solutions for both patients
      and surgeons were often shorter than recommended. Evidence-based guidelines for
      these procedures in veterinary medicine should be established and implemented in
      order to help reduce preventable SSIs, while maintaining efficiency and cost
      effectiveness.

PMID- 24093971
TI  - Interactions affecting the mechanical properties of macromolecular microsphere
      composite hydrogels.
AB  - Macromolecular microsphere composite (MMC) hydrogel is a kind of tough hydrogel
      fabricated by using peroxidized macromolecular microspheres as polyfunctional
      initiating and cross-linking centers (PFICC). The contribution of chemical cross
      linking (covalent bonding) and physical cross-linking (chain entanglement and
      hydrogen bonding) to the mechanical properties are understood by testing the
      hydrogels, which were swollen in water or aqueous urea solutions to different
      water contents. The as-prepared MMC gels exhibited moderate moduli (60-270 kPa),
      high fracture tensile stresses (up to 0.54 MPa), high extensibilities (up to
      2500%), and high fracture energies (270-770 J m(-2)). The moduli of the swollen
      gels decrease dramatically, but there are no significant changes in fracture
      tensile strength and fracture strain, even slight increases. More interestingly,
      the swollen gels show much-enhanced fracture energies, higher than 2000 J m(-2).
      A gradual decrease in the hysteresis ratio and residual strain is also found in
      the cyclic tensile testing of the hydrogels that were swollen to different water
      contents. The covalent bonding determines the tensile strength and fracture
      energy of the MMC gels, whereas the physical entanglement and hydrogen bonding
      among the polymer chains contributes mainly to the modulus of the MMC gels, and
      they are also the main reason for the presence of hysteresis in the loading
      unloading cycles. 

PMID- 24093970
TI  - An explanatory model of factors related to well baby visits by age three years
      for Medicaid-enrolled infants: a retrospective cohort study.
AB  - BACKGROUND: Well baby visits (WBVs) are a cornerstone of early childhood health,
      but few studies have examined the correlates of WBVs for socioeconomically
      vulnerable infants. The study objective was to identify factors related to the
      number of WBVs received by Medicaid-enrolled infants in the first three years of
      life and to present a preliminary explanatory model. METHODS: We analyzed Iowa
      Medicaid claims files and birth certificate data for infants born in calendar
      year 2000 (N = 6,085). The outcome measure was the number of well baby visits
      (WBVs) received by Medicaid-enrolled infants between age 1 and 41 months (range:
      0 to 10). An ecological health model and existing literature were used to
      evaluate 12 observed factors as potential WBV correlates. We ran multiple
      variable linear regression models with robust standard errors (alpha = 0.05).
      RESULTS: There were a number of infant, maternal, and health system factors
      associated with the number of WBVs received by Medicaid-enrolled infants. Infants
      whose mothers had a greater number of prenatal healthcare visits (beta = 0.24 to
      0.28; P = .001) or were married (beta = 0.20; P = .002) received more WBVs.
      Having a chronic health condition (beta = 0.51; P < .0001) and enrollment in a
      case management program (beta = 0.48; P < .0001) were also positively associated
      with WBVs. Eligibility for Medicaid through the Supplemental Security Income
      Program (beta = -0.70; P = .001), increased maternal age (beta = -0.27 to -0.35;
      P = .004), higher levels of maternal education (beta = -0.18; P = .005), maternal
      smoking (beta = -0.13; P = .018), and enrollment in a health maintenance
      organization plan (beta = -1.15; P < .0001) were negatively associated with WBVs.
      There was a significant interaction between enrollment in a health maintenance
      organization plan and enrollment in a Medicaid case management program (P =
      .015). Maternal race, maternal alcohol use during pregnancy, and rurality were
      not significantly related to the number of WBVs. CONCLUSIONS: Multiple infant,
      maternal, and health system variables were related to the number of WBVs received
      by Medicaid-enrolled infants. Additional research is needed to develop strategies
      to optimize access to WBVs for Medicaid-enrolled infants at risk for poor use of
      preventive medical care services.

PMID- 24093972
TI  - Should elderly patients with higher-risk myelodysplastic syndromes undergo
      allogeneic hematopoietic stem cell transplantation?
AB  - Myelodysplastic syndromes (MDS) include a group of hematopoietic malignancies
      characterized by dysplastic changes, ineffective hematopoiesis and variable risk
      of leukemic progression. At diagnosis, 86% of MDS patients are >=60 years.
      Azacitidine, the only drug that prolongs life in high-risk (HR)-MDS patients,
      adds a median of only 9.5 months to life. Allogeneic stem cell transplantation
      (alloSCT) remains the only potentially curative approach. Despite recent
      improvements including use of reduced intensity conditioning (RIC) that decrease
      transplant-related mortality, alloSCT continues to be used rarely in elderly MDS.
      There is paucity of data regarding outcomes of RIC alloSCT in elderly MDS
      patients, especially in direct comparison with azanucleosides. In this paper, the
      authors discuss the recent Markov decision analysis by Koreth et al. in which
      investigators demonstrated superior survival of patients with HR-MDS aged 60-70
      years who underwent RIC alloSCT in comparison with those who were treated with
      azanucleosides.

PMID- 24093975
TI  - High-throughput solvent assisted ionization inlet for use in mass spectrometry.
AB  - In this work we developed a multiplexed analysis platform providing a simple high
      throughput means to characterize solutions. Automated analyses, requiring less
      than 5 s per sample without carryover and 1 s per sample, accepting minor cross
      contamination, was achieved using multiplexed solvent assisted ionization inlet
      (SAII) mass spectrometry (MS). The method involves sequentially moving rows of
      pipet tips containing sample solutions in close proximity to the inlet aperture
      of a heated mass spectrometer inlet tube. The solution is pulled from the
      container into the mass spectrometer inlet by the pressure differential at the
      mass spectrometer inlet aperture. This sample introduction method for direct
      injection of solutions is fast, easily implemented, and widely applicable, as is
      shown by applications ranging from small molecules to proteins as large as
      carbonic anhydrase (molecular weight ca. 29,000). MS/MS fragmentation is
      applicable for sample characterization. An x,y-stage and common imaging software
      are incorporated to map the location of components in the sample wells of a
      microtiter plate. Location within an x,y-array of different sample solutions and
      the relative concentration of the sample are displayed using ion intensity maps.

PMID- 24093973
TI  - Polymyxin B treatment improves bactofection efficacy and reduces cytotoxicity.
AB  - Improvements to bacterial vectors have resulted in nonviral gene therapy vehicles
      that are easily prepared and can achieve high levels of transfection efficacy.
      However, these vectors are plagued by potential cytotoxicity and immunogenicity,
      prompting means of attenuation to reduce unwanted biological outcomes while
      maintaining transfection efficiency. In this study, listeriolysin O (LLO)
      producing Escherichia coli BL21(DE3) strains were pretreated with polymyxin B
      (PLB), a pore-forming antibiotic, and tested as a delivery vector for gene
      transfer to a murine RAW264.7 macrophage cell line using a 96-well high
      throughput assay. PLB treatment resulted in statistically significant higher
      levels of gene delivery and lower cytotoxicity. The results suggest a fine
      balance between bacterial cellular damage, heightened gene and protein release,
      and increased mammalian cell gene delivery. Overall, the approach presented
      provides a simple and effective way to enhance bacterial gene delivery while
      simultaneously reducing unwanted outcomes as a function of using a biological
      vector. 

PMID- 24093977
TI  - Management of tuberculosis in India: time for a deeper dive into quality.

PMID- 24093976
TI  - Do plants mediate their anti-diabetic effects through anti-oxidant and anti
      apoptotic actions? an in vitro assay of 3 Indian medicinal plants.
AB  - BACKGROUND: Both experimental and clinical studies suggest that oxidative stress
      plays a major role in the pathogenesis of both types of diabetes mellitus. This
      oxidative stress leads to beta-cell destruction by apoptosis. Hence exploring
      agents modulating oxidative stress is an effective strategy in the treatment of
      both Type I and Type II diabetes. Plants are a major source of anti-oxidants and
      exert protective effects against oxidative stress in biological systems.
      Phyllanthus emblica, Curcuma longa and Tinospora cordifolia are three such plants
      widely used in Ayurveda for their anti-hyperglycemic activity. Additionally their
      anti-oxidant properties have been scientifically validated in various
      experimental in vitro and in vivo models. Hence the present in vitro study was
      planned to assess whether the anti-hyperglycemic effects of the hydro-alcoholic
      extracts of Phyllanthus emblica (Pe) and Curcuma longa (Cl) and aqueous extract
      of Tinospora cordifolia (Tc) are mediated through their antioxidant and/or anti
      apoptotic property in a streptozotocin induced stress model. METHODS: RINm5F cell
      line was used as a model of pancreatic beta-cells against stress induced by
      streptozotocin (2 mM). Non-toxic concentrations of the plant extracts were
      identified using MTT assay. Lipid peroxidation through MDA release, modulation of
      apoptosis and insulin release were the variables measured to assess
      streptozotocin induced damage and protection afforded by the plant extracts.
      RESULTS: All 3 plants extracts significantly inhibited MDA release from RIN cells
      indicating protective effect against STZ induced oxidative damage. They also
      exhibited a dose dependent anti-apoptotic effect as seen by a decrease in the sub
      G0 population in response to STZ. None of the plant extracts affected insulin
      secretion from the cells to a great extent. CONCLUSION: The present study thus
      demonstrated that the protective effect of the selected medicinal plants against
      oxidative stress induced by STZ in vitro, which was exerted through their anti
      oxidant and anti-apoptotic actions.

PMID- 24093978
TI  - A randomized, double-blind, placebo-controlled trial of ormeloxifene in breast
      pain and nodularity.
AB  - BACKGROUND: Breast pain and non-discrete breast nodularity are common in women.
      METHODS: We did a randomized, double-blind, placebocontrolled trial of oral
      ormeloxifene 30 mg, a selective oestrogen receptor modulator (SERM) or placebo
      twice a week for 3 months in 20-50-year-old women with breast pain with or
      without lumpiness. Women with a discrete benign lump or cancer were excluded from
      the study. Serial assessments of pain on a visual analogue scale and nodularity
      grade on a 5-point ordinal Lucknow-Cardiff scale were done. A total of 151
      patients were randomly allocated to two interventions using a block size of 4.
      RESULTS: Of the 151 patients, 121 (active 57, placebo 64) were available for
      efficacy analysis. The mean pain level showed a systematic downward trend over
      five visits (F=105.23, p<0.0001) that significantly reduced in the active group
      compared to that in the placebo group (F=18.66, p<0.0001). The patterns of
      variation in pain over time for the individual groups differ from the overall
      mean pattern for the two groups and thus from one another (F=44.43, p<0.0001).
      Cumulative frequencies of breast nodularity grades during successive visits
      showed significant improvement (p=0.001) compared to placebo at the end of the
      third month. The effect of the active drug persisted till the completion (6
      months) of treatment (p<0.001). At the last visit, 93.3% of women in the active
      group had grade 2 or lower nodularity as compared to 71.1% in the placebo group.
      Oligomenorrhoea alone was reported by 12 patients. CONCLUSION: Ormeloxifene
      showed significant efficacy for treating breast pain and nodularity.

PMID- 24093979
TI  - Use of and satisfaction with complementary and alternative medicine in four
      chronic diseases: a cross-sectional study from India.
AB  - BACKGROUND: We assessed the extent of use of complementary and alternative
      medicine (CAM) by patients with four chronic diseases-epilepsy, HIV, rheumatoid
      arthritis (RA) and diabetes mellitus (DM)-at a tertiary care, teaching hospital
      of allopathic medicine in India. We also assessed patients' satisfaction with
      CAM. METHODS: Adults attending the outpatient clinics for epilepsy, HIV, RA and
      DM who took CAM were recruited over a period of 16 weeks. After obtaining written
      informed consent, they were administered the 'Treatment Satisfaction
      Questionnaire for Medication' (TSQM)TM to assess satisfaction in domains such as
      effectiveness, no side-effect, convenience and global satisfaction. RESULTS: Of
      the 4664 patients screened, 1619 (34.7%) were using CAM and 650 (40%) of them
      consented to participate. The extent of use of CAM was 63% in patients with DM,
      42.7% in RA, 26.2% in HIV and 7.7% in epilepsy. Ayurveda 57.1% (95% CI 53.27
      60.89) was the most frequently used CAM. Satisfaction in terms of effectiveness
      and global satisfaction was highest among patients with HIV (69.4% and 69.2%,
      respectively) and least among those who had RA (56.6% and 54.1%, respectively).
      High scores were reported to 'no side-effect' domain in all the four diseases.
      The proportion of physicians who were aware about their patients' using CAM was
      100% in patients with RA, 95% in HIV, 74% in epilepsy and 29% in DM. CONCLUSION:
      A large proportion of patients with four chronic diseases reporting to a hospital
      of allopathic medicine in India were also using CAM and were satisfied with its
      use. Given the potential interaction of CAM with allopathic medicines, a history
      of use of CAM should be elicited in clinical practice.

PMID- 24093980
TI  - Prevalence and aetiology of anaemia in lymphoid malignancies.
AB  - BACKGROUND: We prospectively studied the prevalence, type and causes of anaemia
      in newly diagnosed patients with lymphoid malignancies. METHODS: Between January
      2007 and June 2008, a total of 316 newly diagnosed, consecutive patients (aged 15
      years or above) of Hodgkin lymphoma, non-Hodgkin lymphoma and chronic lymphocytic
      leukaemia with anaemia (haemoglobin <11 g/dl), were analysed to determine the
      prevalence and a subgroup of 46 patients was analysed for the cause of anaemia.
      RESULTS: Hodgkin lymphoma, non-Hodgkin lymphoma and chronic lymphocytic leukaemia
      were the diagnoses in 81 (25.8%), 203 (64.7%) and 30 (9.6%) patients,
      respectively. Anaemia was present in 134 patients (42.4%). Anaemia of chronic
      disease was present in 33/46 (71.7%) and iron deficiency in 18/46 (39.1%)
      patients. Vitamin B12 and/or folate deficiency was detected in 10/46 (21.7%)
      patients (B12 deficiency alone in 7, folate deficiency alone in 1 and combined
      B12 and folate deficiency in 2). Autoimmune haemolytic anaemia was detected in
      5/46 (10.9%) although direct Coombs test was positive in 17/46 (37%) patients.
      Among patients with Hodgkin lymphoma and non-Hodgkin lymphoma, anaemia due to
      bone marrow involvement was present in 16/40 (40%). In most patients with bone
      marrow involvement, anaemia was due to other causes. In only 3 patients, anaemia
      was attributable to bone marrow involvement alone. Anaemia was multifactorial in
      18/46 (39.1%) patients. Nutritional deficiency alone or in combination was
      present in 22/46 (47.8%) patients. CONCLUSION: Anaemia is common in lymphoid
      malignancies at initial presentation. Besides managing anaemia of chronic disease
      and bone marrow involvement, nutritional and autoimmune causes should be ruled
      out.

PMID- 24093981
TI  - Bladder decompression for chronic urinary retention may lead to upper tract
      bleeding.
AB  - Haematuria following decompression of a distended bladder is a well known
      condition. The bleeding in such cases originates in the bladder and resolves
      spontaneously. We describe an elderly man who had bleeding from the kidney
      following decompression of the bladder. This resulted in an extensive search for
      an upper tract tumour as a cause for haematuria. 

PMID- 24093983
TI  - Tobacco use and body mass index: do they have synergistic effect on mortality due
      to tuberculosis?

PMID- 24093984
TI  - Heavy consumption of alcohol: a risk factor for cancer deaths?

PMID- 24093982
TI  - P2Y12 inhibitors in acute coronary syndromes: which and when?
AB  - Acute coronary syndromes (ACS) are the commonest acute manifestation of coronary
      artery disease and a major cause of hospitalization and death. Plaque rupture and
      subsequent platelet activation are the key factors in its pathogenesis. Platelet
      inhibitors are crucial in the management of ACS. Aspirin remains the standard
      antiplatelet but use of dual antiplatelet drugs is beneficial in ACS. Platelet
      P2Y12 receptor inhibitors are an important group of antiplatelet compounds that
      can be combined with aspirin in the management of ACS. P2Y12 inhibitors may
      belong to the thienopyridine or nonthienopyridine group of compounds. The former
      (clopidogrel, prasugrel) combine irreversibly with the receptor and therefore
      have a prolonged duration of action. On the other hand, the non-thienopyridine
      compounds (ticagrelor, elinogrel) have a reversible action and hence a shorter
      duration of action. Several new compounds in this group have become or are likely
      to become available. The newer agents have a more uniform and complete
      antiplatelet effect and are much less likely to be affected by genetic
      variability of CYP2C19 enzyme activity compared with that of clopidogrel. Large
      phase 3 trials have shown that ticagrelor and prasugrel reduce major
      cardiovascular events in ACS compared to clopidogrel when given in addition to
      aspirin. This is accompanied by some increase in bleeding. This review discusses
      the properties, clinical profile and possible place of P2Y12 receptor inhibitors
      in clinical practice. 

PMID- 24093985
TI  - Glutamine in critically ill patients.

PMID- 24093986
TI  - Faculty development: why it fails to impress us.

PMID- 24093987
TI  - Development of healthcare services in India.

PMID- 24093989
TI  - National consultation for professionalism in health profession education.

PMID- 24093990
TI  - Notes on confidentiality and disclosure in a diverse world.

PMID- 24093996
TI  - Implementation of ICD-10: constraints and difficulties of healthcare providers.

PMID- 24093997
TI  - Treatment of "pernicious anaemia of pregnancy" and "tropical anaemia" with
      special reference to yeast extract as a curative agent. 1931.

PMID- 24093998
TI  - India's contribution to folic acid in medicine.

PMID- 24094007
TI  - The four mechanisms of dental resorption initiation.
AB  - The aim of this study is to present a classification with a clinical application
      for root resorption, so that diagnosis will be more objective and immediately
      linked to the source of the problem, leading the clinician to automatically
      develop the likely treatment plan with a precise prognosis. With this purpose, we
      suggest putting together all diagnosed dental resorptions into one of these four
      criteria: 1) Root resorption caused by cementoblast cell death, with preservation
      of the Malassez epithelial rests. 2) Root resorption by cementoblasts and
      Malassez epithelial rests death. 3) Dental resorption by odontoblasts cell death
      with preservation of pulp vitality. 4) Dental resorption by direct exposure of
      dentin to gingival connective tissue at the cementoenamel junction gaps. 

PMID- 24094006
TI  - Differential adaptation to multi-stressed conditions of wine fermentation
      revealed by variations in yeast regulatory networks.
AB  - BACKGROUND: Variation of gene expression can lead to phenotypic variation and
      have therefore been assumed to contribute the diversity of wine yeast
      (Saccharomyces cerevisiae) properties. However, the molecular bases of this
      variation of gene expression are unknown. We addressed these questions by
      carrying out an integrated genetical-genomic study in fermentation conditions. We
      report here quantitative trait loci (QTL) mapping based on expression profiling
      in a segregating population generated by a cross between a derivative of the
      popular wine strain EC1118 and the laboratory strain S288c. RESULTS: Most of the
      fermentation traits studied appeared to be under multi-allelic control. We mapped
      five phenotypic QTLs and 1465 expression QTLs. Several expression QTLs overlapped
      in hotspots. Among the linkages unraveled here, several were associated with
      metabolic processes essential for wine fermentation such as glucose sensing or
      nitrogen and vitamin metabolism. Variations affecting the regulation of drug
      detoxification and export (TPO1, PDR12 or QDR2) were linked to variation in four
      genes encoding transcription factors (PDR8, WAR1, YRR1 and HAP1). We demonstrated
      that the allelic variation of WAR1 and TPO1 affected sorbic and octanoic acid
      resistance, respectively. Moreover, analysis of the transcription factors
      phylogeny suggests they evolved with a specific adaptation of the strains to wine
      fermentation conditions. Unexpectedly, we found that the variation of
      fermentation rates was associated with a partial disomy of chromosome 16. This
      disomy resulted from the well known 8-16 translocation. CONCLUSIONS: This large
      data set made it possible to decipher the effects of genetic variation on gene
      expression during fermentation and certain wine fermentation properties. Our
      findings shed a new light on the adaptation mechanisms required by yeast to cope
      with the multiple stresses generated by wine fermentation. In this context, the
      detoxification and export systems appear to be of particular importance, probably
      due to nitrogen starvation. Furthermore, we show that the well characterized 8-16
      translocation located in SSU1, which is associated with sulfite resistance, can
      lead to a partial chromosomic amplification in the progeny of strains that carry
      it, greatly improving fermentation kinetics. This amplification has been detected
      among other wine yeasts.

PMID- 24094005
TI  - CD164 regulates the tumorigenesis of ovarian surface epithelial cells through the
      SDF-1alpha/CXCR4 axis.
AB  - BACKGROUND: CD164 (endolyn), a sialomucin, has been reported to play a role in
      the proliferation, adhesion, and differentiation of hematopoietic stem cells. The
      potential association of CD164 with tumorigenicity remains unclear. METHODS: The
      clinicopathological correlation of ovarian cancer with CD164 was assessed in a 97
      patient tumor tissue microarray. Overexpression or silence CD164 was to analyze
      the effect of CD164 on the proliferation, colony formation and apoptosis via a
      mouse xenograft and western blotting analysis. The subcellular localization of
      CD164 was collected in the immunohistochemical and confocal analysis. RESULTS:
      Our data demonstrated that higher expression levels of CD164 were identified in
      malignant ovarian cancer cell lines, such as SKOV3 and HeyA8. The
      clinicopathological correlation analysis showed that the upregulation of CD164
      protein was significantly associated with tumor grade and metastasis. The
      overexpression of CD164 in human ovarian epithelial surface cells promoted
      cellular proliferation and colony formation and suppressed apoptosis. These
      tumorigenicity effects of CD164 were reconfirmed in a mouse xenograft model. We
      also found that the overexpression of CD164 proteins increased the amounts of
      CXCR4 and SDF-1alpha and activated the SDF-1alpha/CXCR4 axis, inducing colony and
      sphere formation. Finally, we identified the subcellular localization of CD164 in
      the nucleus and cytosol and found that nuclear CD164 might be involved in the
      regulation of the activity of the CXCR4 promoter. CONCLUSIONS: Our findings
      suggest that the increased expression of CD164 is involved in ovarian cancer
      progression via the SDF-1alpha/CXCR4 axis, which promotes tumorigenicity. Thus,
      targeting CD164 may serve as a potential ovarian cancer biomarker, and targeting
      CD164 may serve as a therapeutic modality in the management of high-grade ovarian
      tumors.

PMID- 24094008
TI  - Sagittal changes in lower incisors by the use of lingual arch.
AB  - OBJECTIVE: The objective of this study was to evaluate a sagittal variation on
      the lower incisors with the use of the lingual arch on the transition from mixed
      to permanent dentition. METHODS: The sample was constituted of 44 Caucasian
      patients (26 girls and 18 boys), divided in two groups: CG, control group,
      monitoring the lower arch space with no orthodontic/orthopedic treatment during
      the rated period (n = 14); EG, experimental group, presenting anterior inferior
      mild crowding and installation of the lingual arch for space maintenance (n =
      30). The position of the lower incisors was analyzed on computerized
      cephalometric tracings performed at the beginning of the monitoring (T1) and at
      the end, on the permanent dentition (T2). In order to evaluate the position of
      the incisors it was used Tweed and Steiner measurements: IMPA, 1.NB and 1-NB. The
      alterations were analyzed through the "t" test for paired samples, while the
      differences between the groups were analyzed through the "t" test for independent
      samples, as for sexual dimorphism. RESULTS: The values in T2 were greater in
      relation to T1 for all measurements on EG (IMPA, p = 0.038; 1.NB, p = 0.007 and 1
      NB, p < 0.0001). On comparing the differences (T2-T1) between CG and EG, it can
      be gauged differences significantly superior for measure 1.NB (p = 0.002) and 1
      NB (p < 0.0001) on EG. There was no statistically significant difference between
      genres. CONCLUSIONS: It was concluded that the lower incisors were projected
      after using the lingual arch to control the space on the transition from mixed to
      permanent dentition, however, within acceptable standards, not having difference
      between genres.

PMID- 24094009
TI  - Mechanical evaluation of quad-helix appliance made of low-nickel stainless steel
      wire.
AB  - OBJECTIVE: The objective of this study was to test the hypothesis that there is
      no difference between stainless steel and low-nickel stainless steel wires as
      regards mechanical behavior. Force, resilience, and elastic modulus produced by
      Quad-helix appliances made of 0.032-inch and 0.036-inch wires were evaluated.
      METHODS: Sixty Quad-helix appliances were made, thirty for each type of alloy,
      being fifteen for each wire thickness, 0.032-in and 0.036-in. All the archwires
      were submitted to mechanical compression test using an EMIC DL-10000 machine
      simulating activations of 4, 6, 9, and 12 mm. Analysis of variance (ANOVA) with
      multiple comparisons and Tukey's test were used (p < 0.05) to assess force,
      resilience, and elastic modulus. RESULTS: Statistically significant difference in
      the forces generated, resilience and elastic modulus were found between the 0.032
      in and 0.036-in thicknesses (p < 0.05). CONCLUSIONS: Appliances made of low
      nickel stainless steel alloy had force, resilience, and elastic modulus similar
      to those made of stainless steel alloy.

PMID- 24094010
TI  - Transversal changes in dental arches from non-extraction treatment with self
      ligating brackets.
AB  - OBJECTIVE: The present study aimed at analyzing, with the use of dental casts,
      the transverse changes of the upper and lower dental arches, after non-extraction
      orthodontic treatment, with self-ligating brackets. METHODS: The sample comprised
      29 patients, all presenting Class I malocclusion with upper and lower crowding of
      at least 4 mm and treated only with a fixed appliance, without stripping,
      extraction or distalization. The dental casts were obtained before and after
      leveling with 0.019 x 0.025-in stainless steel archwires. CONCLUSIONS: The
      results indicated that the majority of transverse changes occurred at the
      premolar areas, both the first and the second, as well as on the upper and lower
      dental arches. The intercanine distance increased 0.75 mm, on average, in the
      upper arch and 1.96 mm in the lower arch. The molars also demonstrated a tendency
      towards an increase in their transverse dimension, however, at a lower intensity
      comparing to premolars. All measurements presented statistically significant
      differences with the exception of the maxillary second molars.

PMID- 24094011
TI  - Long-term stability of maxillary anterior alignment in non-extraction cases.
AB  - OBJECTIVE: The purpose of this retrospective study was to evaluate long-term
      stability of maxillary incisors alignment in cases submitted to non-extraction
      orthodontic treatment. METHODS: The sample comprised 23 patients (13 female; 10
      male) at a mean initial age of 13.36 years (SD = 1.81 years), treated with fixed
      appliances. Dental cast measurements were obtained at three different time points
      (T1 - pretreatment, T2 - posttreatment and T3 - long-term posttreatment).
      Variables assessed in maxillary arch were Little Irregularity Index, intercanine,
      interpremolar and intermolar widths, arch length and perimeter. The statistical
      analysis was performed by one-way ANOVA and Tukey tests when necessary. Pearson'
      correlation coefficients were used to investigate possible associations between
      the evaluated variables. RESULTS: There was no significant change in most arch
      dimension measurements during and after treatment, however, during the long-term
      posttreatment period, it was observed a significant maxillary incisors crowding
      relapse. CONCLUSIONS: The maxillary incisors irregularity increased significantly
      (1.52 mm) during long-term posttreatment. None of the studied clinical factors
      demonstrated to be predictive of the maxillary crowding relapse.

PMID- 24094012
TI  - Influence of surface treatment on shear bond strength of orthodontic brackets.
AB  - INTRODUCTION: The shear bond strength of orthodontic brackets bonded to micro
      hybrid and micro-particulate resins under different surface treatment methods was
      assessed. METHODS: Two hundred and eighty test samples were divided into 28
      groups (n = 10), where 140 specimens were filled with Durafill micro-particulate
      resin and 140 with Charisma composite. In 140 samples, a coupling agent (silane)
      was applied. The surface treatment methods were: Phosphoric and hydrofluoric acid
      etching, sodium bicarbonate and aluminum oxide blasting, stone and burs. A
      Universal Instron Machine was used to apply an occlusal shear force directly to
      the resin composite bracket surface at a speed of 0.5 mm/min. The means were
      compared using analysis of variance and multivariate regression to assess the
      interaction between composites and surface treatment methods. RESULTS: Means and
      standard deviations for the groups were: Sodium bicarbonate jet 11.27 +/- 2.78;
      burs 9.26 +/- 3.01; stone 7.95 +/- 3.67; aluminum oxide blasting 7.04 +/- 3.21;
      phosphoric acid 5.82 +/- 1.90; hydrofluoric acid 4.54 +/- 2.87, and without
      treatment 2.75 +/- 1.49. An increase of 1.94 MPa in shear bond strength was seen
      in Charisma groups. Silane agent application reduced the Charisma shear bond
      strength by 0.68 Mpa, but increased Durafill means for bicarbonate blasting
      (0.83), burs (0.98) and stone drilling (0.46). CONCLUSIONS: The sodium
      bicarbonate blasting, burs and stone drilling methods produced adequate shear
      bond strength and may be suitable for clinical use. The Charisma micro hybrid
      resin composite showed higher shear bond means than Durafill micro particle
      composite.

PMID- 24094013
TI  - The evolution of cephalometric diagnosis in orthodontics.
AB  - INTRODUCTION: Although the development of CT have represented a landmark in
      diagnostic imaging, its use in Dentistry turned out very discretely over the
      years. With the appearance of programs for analysis of three-dimensional images,
      specific for Orthodontics and Orthognathic surgery, a new reality is being built.
      OBJECTIVE: The authors of this study aim to inform the orthodontic society of
      fundamentals about digital cephalometric radiographic image and computed
      tomography, discussing about: Field of view (FOV), radiation doses, demands for
      the use in Orthodontics and radiographic simulations.

PMID- 24094014
TI  - Transverse maxillary and mandibular growth during and after bionator therapy:
      study with metallic implants.
AB  - INTRODUCTION: This study evaluated posteroanterior cephalograms before and after
      treatment and long term follow-up of Class II division 1 patients treated with
      bionator. OBJECTIVE: The objective was to demonstrate the transverse growth of
      maxilla and mandible during and after bionator therapy. METHODS: Measurement of
      transverse dimensions between posterior maxillary and mandibular implants, as
      well as the distances between the buccal, gonial and antegonial points were
      recorded. Measurements were analyzed at three periods: T1 - before bionator
      therapy, T2 - after bionator therapy and T3 - 5.74 years after T2. RESULTS: There
      was statistically significant transverse increase due to growth and/or treatment
      for all variables, except for the distance between the anterior maxillary
      implants. CONCLUSIONS: During the study period only the anterior maxillary area
      did not show transverse growth.

PMID- 24094015
TI  - The influence of patient's motivation on reported pain during orthodontic
      treatment.
AB  - INTRODUCTION: Patients usually experience pain during orthodontic treatment. This
      fact can affect cooperation and the development of treatment. Reporting pain
      during treatment seems to be influenced by emotional aspects such as the
      patient's motivation. OBJECTIVE: To assess the relationship between patient's
      motivation and the intensity of reported pain during two stages of treatment.
      METHODS: Twenty males (11-37 years old) answered a questionnaire divided into
      five categories regarding their motivation towards treatment. The subjects were
      studied for 14 days (7 days with bonded brackets and 7 days with the initial arch
      inserted) and the intensity of pain was evaluated on a daily basis. All the
      issues, including the intensity of pain, were measured through the visual analog
      scale (VAS). RESULTS: The VAS-associated questionnaire proved to have good
      temporal reliability and reasonable internal consistency, being that the
      "perceived severity" domain had the greatest, although not significant (p =
      0.196) correlation with pain intensity. Only the question asking the patients if
      they thought that their teeth were too uneven showed a positive correlation with
      pain intensity (p = 0.048). CONCLUSIONS: The results seem to indicate that the
      five categories related to treatment motivation cannot be used to predict
      discomfort during treatment. In addition, patients who think their teeth are too
      uneven may experience more severe pain due to greater force application after
      insertion of the initial arch.

PMID- 24094016
TI  - Comparative evaluation of cephalometric occlusal characteristics between the long
      face pattern and pattern I.
AB  - OBJECTIVE: To compare the cephalometric and intraoral characteristics between
      Long Face pattern and Pattern I patients, besides evaluating associations between
      subjective facial patterns, cephalometric facial patterns and the intraoral
      characteristics. METHODS: Through evaluation of frontal and right side extraoral
      photographs, three previously calibrated and experienced examiners selected 30
      Long Face patients (Group 1) and 30 Pattern I patients (Group 2), aged between 9
      and 19 years, of both genders. The cephalometric characteristics were assessed by
      the following variables: SN.GoGn, NS.Gn, AIFH, SNA, SNB, ANB, 1.1, 1.NA,1-NA,
      1.NB, 1-NB, NA.Po, nasolabial angle and H-Nose. Clinical evaluations were also
      performed to determine the presence of posterior crossbite, anterior open bite
      and type of Angle's malocclusion. The cephalometric data were compared by
      independent t test. The chi-square test was used to evaluate the association
      between qualitative variables. RESULTS: Significant differences were observed
      between groups regarding the variables SN.GoGn, NS.Gn, AIFH, ANB, NA.Pog, 1-NA,
      1.NB and 1-NB, with an increase of these measures in Group 1. There were also
      significant differences between groups on variable 1.1, being lower in Group 1
      than in Group 2. CONCLUSIONS: The Long Face was associated to Angle Class II
      malocclusion, to the presence of posterior crossbite and to anterior open bite.
      The Long Face subjective facial pattern was associated to dolichofacial
      cephalometric pattern.

PMID- 24094017
TI  - Surgical-orthodontic treatment of Class III malocclusion with agenesis of lateral
      incisor and unerupted canine.
AB  - INTRODUCTION: Orthodontic-surgical treatment was performed in patient with
      skeletal Class III malocclusion due to exceeding mandibular growth. Patient also
      presented upper and lower dental protrusion, overjet of -3.0 mm, overbite of -1.0
      mm, congenital absence of tooth #22, teeth #13 and supernumerary impaction, tooth
      #12 with conoid shape and partly erupted in supraversion, prolonged retention of
      tooth #53, tendency to vertical growth of the face and facial asymmetry. The
      discrepancy on the upper arch was -2.0 mm and -5.0 mm on the lower arch. METHODS:
      The presurgical orthodontic treatment was performed with extraction of the teeth
      #35 and #45. On the upper arch, teeth #53, #12 and supernumerary were extracted
      to accomplish the traction of the impacted canine. The spaces of the lower
      extractions were closed with mesialization of posterior segment. After aligning
      and leveling the teeth, extractions spaces closure and correct positioning of
      teeth on the bone bases, the correct intercuspation of the dental arch, with
      molars and canines in Angle's Class I, coincident midline, normal overjet and
      overbite and ideal torques, were evaluated through study models. The patient was
      submitted to orthognathic surgery and then the postsurgical orthodontic treatment
      was finished. RESULTS: The Class III malocclusion was treated establishing
      occlusal and facial normal standards.

PMID- 24094018
TI  - Evaluation of metallic brackets adhesion after the use of bleaching gels with and
      without amorphous calcium phosphate (ACP): in vitro study.
AB  - OBJECTIVE: To evaluate in vitro the effects of tooth whitening using gel with
      Amorphous Calcium Phosphate (ACP) on the bond strength of metal brackets.
      METHODS: Thirty-six bovine incisors were sectioned at the crown-root interface,
      and the crowns were then placed in PVC cylinders. The specimens were divided into
      3 groups (n = 12) according to whitening treatment and type of gel used, as
      follows: G1 (control) - no whitening; G2 - whitening with gel not containing ACP
      (Whiteness Perfect - FGM), G3 - whitening with gel containing ACP (Nite White ACP
      - Discus Dental). Groups G2 and G3 were subjected to 14 cycles of whitening
      followed by an interval of 15 days before the bonding of metal brackets. Shear
      bond strength testing was performed on a Kratos universal test machine at a speed
      of 0.5 mm/min. After the mechanical test, the specimens were assessed to
      determine the adhesive remnant index (ARI). The results were subjected to ANOVA,
      Tukey's test and Kruskal-Wallis test (5%). RESULTS: Significant differences were
      noted between the groups. Control group (G1 - 11.10 MPa) showed a statistically
      higher shear bond strength than the groups that underwent whitening (G2 - 5.40
      Mpa, G3 - 3.73 MPa), which did not differ from each other. There were no
      significant differences between the groups in terms of ARI. CONCLUSIONS: Tooth
      whitening reduces the bond strength of metal brackets, whereas the presence of
      ACP in the whitening gel has no bearing on the results.

PMID- 24094019
TI  - Superficial morphology and mechanical properties of in vivo aged orthodontic
      ligatures.
AB  - INTRODUCTION: The degradation of elastic ligatures in the oral environment
      results in the need of periodic replacement to maintain the optimal force during
      the orthodontic treatment. The purpose of this study was to perform a clinical
      prospective randomized study of the degradation of orthodontic elastomeric
      ligatures in the oral environment by scanning electron microscopy (SEM) and
      tensile strength test. METHODS: Two hundred elastic ligatures were randomly
      selected and placed around the brackets of 5 volunteers and removed in groups of
      10, at different times (1, 2, 3, and 4 weeks). The control group was performed by
      another fifty ligatures which were not submitted to the oral degradation. The
      analyses were done by scanning electron microscopy (SEM) and strength mechanical
      test. RESULTS: The tensile strength test results showed reduction in the ultimate
      strength values after four weeks ageing in the oral environment and no
      statistical difference in the yield strength values (p < 0.05). The orthodontic
      elastomeric ligatures surface was significantly degraded in the oral cavity after
      four weeks. The elastomeric degradation began in the first week when the increase
      in the roughness could be detected just in some areas. Afterwards, the surface
      became gradually rougher and, after 4 weeks, it was totally rough with some crack
      areas. CONCLUSIONS: The elastic ligatures aged in the oral environment showed
      higher superficial degradation and lower loss of mechanical properties after the
      maximum experimental period.

PMID- 24094020
TI  - Time of guard of orthodontic records versus legal time for their prescription.
AB  - INTRODUCTION: After promulgation and wider dissemination of the Code of Consumer
      Protection (CCP), there was an increase in the number of legal conflicts between
      patients and dentists, leading these health professionals to increasingly guard
      themselves from possible lawsuits. As such, it becomes critical the preparation
      of an adequate and complete clinical record, even though the keeping time remains
      uncertain. OBJECTIVE: To review the literature and discuss the keeping time of
      orthodontic records versus the legal time for their prescription, as well as to
      propose a model of a Term upon Completion of Dental Treatment. CONCLUSIONS: It is
      advised to return part of the clinical records to their rightful owners by means
      of an itemized receipt. The Term upon Completion reflects the patient's awareness
      and could be considered by the CCP as the initial term of the prescription time,
      because it implicates that the patient recognizes the quality of service provided
      and satisfactory results achieved.

PMID- 24094021
TI  - Short-term efficacy of mandibular advancement splint in treatment of obstructive
      sleep apnea-hypopnea syndrome.
AB  - OBJECTIVE: The aim of the present study was to determine the short-term efficacy
      of treatment for snoring and obstructive sleep apnea-hypopnea syndrome (OSAHS)
      using a mandibular advancement splint. METHODS: The sample comprised 20 patients
      (13 men and 7 women; mean age = 48 years; mean body mass index = 27.07) with
      OSAHS. Polysomnograms were performed before and 60 days after mandibular
      advancement splint therapy. RESULTS: There was a significant reduction in the
      apnea-hypopnea index (AHI) following treatment (mean pretreatment AHI = 20.89 +/-
      17.9 versus mean posttreatment AHI = 4.43 +/- 3.09) (p < 0.05). The snoring
      reduced and the sleep efficiency improved, as registered by polysomnograms (p <
      0.05). CONCLUSIONS: The sleep quality improved in patients using mandibular
      advancement splint. Further studies evaluating long-term effects are needed.

PMID- 24094022
TI  - In vitro analysis of shear bond strength and adhesive remnant index comparing
      light curing and self-curing composites.
AB  - OBJECTIVE: To evaluate, in vitro, the shear bond strength of self-curing
      (ConciseTM - 3M and Alpha Plast - DFL) and light-curing composites (TransbondTM
      XT - 3M and Natural Ortho - DFL) used in orthodontics bonding, associated to
      Morelli metal brackets, with further analysis of adhesive remnant index (ARI) and
      enamel condition in scanning electron microscopy (SEM). METHODS: Forty human
      premolars, just extracted and stored in physiologic solution 0.9 % were used.
      Randomly, these samples were divided in four groups: G1 group, the brackets were
      bonded with ConciseTM - 3M composite; in G2 group, Alpha Plast - DFL composite
      was used; in G3 group, TransbondTM XT - 3M was used; in G4 group, Natural Ortho -
      DFL composite was used. These groups were submitted to shear strength tests in
      universal testing machine, at 0.5 mm per minute speed. RESULTS: Statistical
      difference between G3 and G4 groups was recorded, as G4 showing higher strength
      resistance than G3. In the other hand, there were no statistical differences
      between G1, G2 and G3 and G1, G2 and G4 groups. ARI analysis showed that there
      was no statistical difference between the groups, and low scores were recorded
      among then. The scanning electron microscopy (SEM) analysis revealed the
      debonding spots and the enamel surface integrity. CONCLUSIONS: Shear bond
      strength was satisfactory and similar between the composites, however Natural
      Ortho - DFL revealed best comparing to TransbondTM XT - 3M.

PMID- 24094023
TI  - Comparison of mesiodistal tooth widths in Caucasian, African and Japanese
      individuals with Brazilian ancestry and normal occlusion.
AB  - OBJECTIVE: To observe the presence of sexual dimorphism and compare the
      mesiodistal width of the teeth in Caucasian, African and Japanese individuals
      with Brazilian ancestry not orthodontically treated and with normal occlusion.
      METHODS: One hundred pairs of dental casts were used. It was measured, from first
      molar to first molar in both arches, the teeth's mesiodistal widths, using a
      digital caliper. For the statistical analysis of results Kolmogorov-Smirnov, t
      test, ANOVA and Tukey's test (p < 0.05) were used. RESULTS: Sexual dimorphism
      occurred on the three evaluated groups, and the highest mesiodistal widths were
      found in males. There was statistically significant difference between racial
      groups in all evaluated teeth in males. However, in females, this same difference
      was found only on upper lateral incisor and first molar; and lower lateral
      incisor, canine, first premolar and first molar. CONCLUSIONS: Most of mesiodistal
      measures present particular characteristics in relation to gender, with higher
      values for males, and to race, with a tendency for African to present greater
      mesiodistal distance of the teeth, followed by Japanese and Caucasians,
      respectively, important for the correct diagnosis and orthodontic planning.

PMID- 24094024
TI  - Deformation of elastomeric chains related to the amount and time of stretching.
AB  - OBJECTIVE: To investigate a potential relationship between degree of stretching
      and resulting permanent deformation of elastomeric chains (ECs) as well as
      whether or not stretching time has any bearing on the degree of permanent
      deformation. METHODS: Five-module segments of closed elastomeric chains
      manufactured by 3M Unitek were stretched to 10-100% of their original length in
      devices especially designed for this purpose, remaining submerged in artificial
      saliva at 37 +/- 1 degrees  C and were removed sequentially after 1, 2, 3 and 4
      weeks. Upon removal, each segment was measured and, once recorded the values,
      were statistically analyzed with the purpose of assessing the degree of permanent
      deformation. CONCLUSIONS: It was concluded that permanent deformation is directly
      proportional to the degree of stretching of the ECs assessed. The mean
      percentages found were 8.4% to 10% of stretching, and exceeding 20% (21.3%) when
      stretched by 40%, and reaching 56.6% permanent deformation when stretched 100% of
      their original length. Finally, the highest percentage of permanent deformation
      occurred during the first week and was not statistically significant after this
      period.

PMID- 24094025
TI  - Cephalometric analysis for the diagnosis of sleep apnea: a comparative study
      between reference values and measurements obtained for Brazilian subjects.
AB  - OBJECTIVE: To verify if the reference values of Sleep Apnea cephalometric
      analysis of North American individuals are similar to the ones of Brazilian
      individuals presenting no craniofacial anomalies. The study also aimed to
      identify craniofacial alterations in Obstructive Sleep Apnea-Hypopnea Syndrome
      (OSAHS) patients in relation to individuals without clinical characteristics of
      the disease through this cephalometric analysis. METHODS: It were used 55 lateral
      cephalograms consisting of 29 for the control group of adult individuals without
      clinical characteristics of OSAHS and 26 apneic adults. All radiographs were
      submitted to Sleep Apnea cephalometric analysis through Radiocef Studio 2.0. The
      standard values of this analysis were compared, by means of z test, to the ones
      obtained from the control group and these were compared to values from apneic
      group through Student's t test. RESULTS: There were no significant differences
      between values obtained from control group and standard values. On the group of
      OSAHS patients it was observed a decrease on the dimensions of upper airways and
      an increase on the soft palate length. CONCLUSIONS: The standard values of Sleep
      Apnea analysis can be used as reference in Brazilian individuals. Besides,
      through lateral cephalograms it was possible to identify craniofacial alterations
      in OSAHS patients.

PMID- 24094026
TI  - Angle Class I malocclusion treated with lower incisor extraction.
AB  - In planning orthodontic cases that include extractions as an alternative to solve
      the problem of negative space discrepancy, the critical decision is to determine
      which teeth will be extracted. Several aspects must be considered, such as
      periodontal health, orthodontic mechanics, functional and esthetic alterations,
      and treatment stability. Despite controversies, extraction of teeth to solve
      dental crowding is a therapy that has been used for decades. Premolar extractions
      are the most common, but there are situations in which atypical extractions
      facilitate mechanics, preserve periodontal health and favor maintenance of the
      facial profile, which tends to unfavorably change due to facial changes with age.
      The extraction of a lower incisor, in selected cases, is an effective approach,
      and literature describes greater post-treatment stability when compared with
      premolar extractions. This article reports the clinical case of a patient with
      Angle Class I malocclusion and upper and lower anterior crowding, a balanced face
      and harmonious facial profile. The presence of gingival and bone recession
      limited large orthodontic movements. The molars and premolars were well occluded,
      and the discrepancy was mainly concentrated in the anterior region of the lower
      dental arch. The extraction of a lower incisor in the most ectopic position and
      with compromised periodontium, associated with interproximal stripping in the
      upper and lower arches, was the alternative of choice for this treatment, which
      restored function, providing improved periodontal health, maintained facial
      esthetics and allowed finishing with a stable and balanced occlusion. This case
      was presented to the Brazilian Board of Orthodontics and Dentofacial Orthopedics
      (BBO), as part of the requirements for obtaining the BBO Diplomate title. 

PMID- 24094027
TI  - Brachycephalic, dolichocephalic and mesocephalic: Is it appropriate to describe
      the face using skull patterns?
AB  - The use of a standardized terminology in the medical sciences is essential for
      both clinical practice and scientific research. In addition to facilitating
      communication between professionals, it enhances the reliability of comparisons
      made between studies from different areas, thereby contributing to a higher level
      of scientific evidence. Examples of attempts made to standardize the terminology
      in other areas dedicated to the study of craniofacial morphology can be found in
      the literature. On the other hand, one can find in the orthodontic literature a
      variety of terms that render the consensus and communication between
      orthodontists and other researchers even more problematic. As an example, one
      could cite the use of the terms brachyfacial, mesofacial and dolichofacial, which
      form part of a cranial index terminology used to describe facial types. Thus, a
      reflection on the origin and differences of the terms used to describe the human
      facial phenotype may pave the way toward a consensus regarding the meaning that
      best represents the craniofacial patterns. 

PMID- 24094028
TI  - CD24+/CD38- as new prognostic marker for non-small cell lung cancer.
AB  - BACKGROUND: Lung cancer is the leading cause of death among cancers in the world.
      The annual death toll due to this disease exceeds the combined deaths caused by
      colon, breast, prostate, and pancreatic cancers. As a result, there has been a
      tremendous effort to identify new biomarkers for early detection and diagnosis of
      lung cancer. METHODS: In this study we report the results of screening a panel of
      eight non-small cell lung cancer (NSCLC) cell lines originating from different
      subtypes of lung cancer in an attempt to identify potential biomarkers unique to
      this disease. We used real-time polymerase chain reaction and flow cytometry
      techniques to analyze the expression of ALDHA1, EpCAM, CD133, CD24, and CD38 in
      this panel. RESULTS: We demonstrate for the first time that the majority of NSCLC
      cells do not express levels of CD38 that would qualify it as a new biomarker for
      the disease. In contrast, we found that CD24 is over-expressed in 6 out of 8 of
      the cell lines. The combined CD24+/CD38-/low phenotype was detected in 50% of the
      cell lines that are also positive for CD133 and EpCAM. CONCLUSIONS: We report
      that CD24+/CD38-/low signature could potentially be used as a new biomarker for
      the early detection of NSCLC.

PMID- 24094029
TI  - Increased serum prolactin levels in drug-naive first-episode male patients with
      schizophrenia.
AB  - BACKGROUND: Prolactin is a hormone receiving considerable attention in
      psychiatry. Increased serum prolactin level is frequently associated with
      dopamine blocking antipsychotics. Furthermore, decreased prolactin level was
      considered a reflector of the effect of antipsychotics. However, there is
      restricted numbers of investigations that researched baseline prolactin levels in
      first-episode patients with schizophrenia. AIMS: We purpose to investigate serum
      baseline prolactin levels in drug-naive first-episode patients with schizophrenia
      (FES) and to explore the differences in serum prolactin levels between FES, drug
      free schizophrenic patients (DFS) and healthy controls (HC). MATERIAL AND
      METHODS: The study was conducted in the Departments of Psychiatry, Golbasi Hasvak
      and Kirklareli State Hospitals, Turkey. Thirty male FES, 41 male DFS and 32 male
      HC were included in study. All participants were clinically examined and
      individually interviewed. Before initiating any pharmacological treatment, 5 ml
      of venous blood was collected to measure serum prolactin levels between 08:00 and
      10:00 h, which was determined by radioimmunoassay (RIA). Prolactin levels were
      also collected from the consenting HC using the same assay. RESULTS: The mean age
      was higher in the DFS group. The mean score of Brief Psychiatric Rating Scale was
      higher in the FES group and mean score of Scale for the Assessment of Negative
      Symptoms was higher in the DFS group. The mean value of prolactin was higher in
      the FES group (34.1 +/- 19.9 ng/dl) compared with DFS (17.9 +/- 6.5 ng/dl) and HC
      (9.7 +/- 2.3 ng/dl) (F = 35.5, P < 0.001). Additionally, the mean value of serum
      prolactin is higher in the DFS group compared with HC (P < 0.001). CONCLUSION: To
      our knowledge, this study is the first to demonstrate higher serum prolactin
      levels in male FES compared with male DFS and male HC. Prolactin might act as a
      protective factor while first episode of schizophrenia is experienced. Future
      studies are needed to provide the role of prolactin in schizophrenia.

PMID- 24094030
TI  - Aggression and violence in contemporary mental health care: heading in the right
      direction?

PMID- 24094031
TI  - The relationship between breakfast skipping, chronotype, and glycemic control in
      type 2 diabetes.
AB  - Breakfast skipping is associated with obesity and an increased risk of type 2
      diabetes. Later chronotypes, individuals who have a preference for later bed and
      wake times, often skip breakfast. The aim of the study was to explore the
      relationships among breakfast skipping, chronotype, and glycemic control in type
      2 diabetes patients. We collected sleep timing and 24-h dietary recall from 194
      non-shift-working type 2 diabetes patients who were being followed in outpatient
      clinics. Mid-sleep time on free days (MSF) was used as an indicator of
      chronotype. Hemoglobin A1C (HbA1C) values were obtained from medical records.
      Hierarchical linear regression analyses controlling for demographic, sleep, and
      dietary variables were computed to determine whether breakfast skipping was
      associated with HbA1C. Additional regression analyses were performed to test if
      this association was mediated by chronotype. There were 22 participants (11.3%)
      who self-reported missing breakfast. Breakfast skippers had significantly higher
      HbA1C levels, higher body mass indices (BMI), and later MSF than breakfast
      eaters. Breakfast skipping was significantly associated with higher HbA1C values
      (B = 0.108, p = 0.01), even after adjusting for age, sex, race, BMI, number of
      diabetes complications, insulin use, depressive symptoms, perceived sleep debt,
      and percentage of daily caloric intake at dinner. The relationship between
      breakfast skipping and HbA1C was partially mediated by chronotype. In summary,
      breakfast skipping is associated with a later chronotype. Later chronotype and
      breakfast skipping both contribute to poorer glycemic control, as indicated by
      higher HbA1C levels. Future studies are needed to confirm these findings and
      determine whether behavioral interventions targeting breakfast eating or sleep
      timing may improve glycemic control in patients with type 2 diabetes. 

PMID- 24094033
TI  - The interference of monoclonal antibodies with laboratory diagnosis: clinical and
      diagnostic implications.
AB  - Diagnostic test interference is due to the presence of material that falsely
      changes an analytic test result. The development of monoclonal antibodies is
      discussed with focus on their extensive use as both therapeutic and diagnostic
      agents. In this review the interference of monoclonal antibodies with laboratory
      test methods and the potential impact on clinical care is addressed. Recognition
      of the types of interference, endogenous and exogenous, and the varied mechanisms
      by which monoclonal antibodies may cause interference are discussed in this
      report. Review of the literature identifies cases which exemplify the issues
      facing laboratorians and clinicians and describe the impact on patients.
      Approaches to reducing and eliminating sources of interference are also
      addressed. Education of ordering clinicians concerning the possibility of
      interference in at-risk patients is key in limiting the impact on care.
      Laboratorians and medical practitioners should be cognizant of the risk of
      interference to avoid incorrect management of patients. 

PMID- 24094034
TI  - Depolymerization-powered autonomous motors using biocompatible fuel.
AB  - We report the design of autonomous motors powered by the rapid depolymerization
      reaction of poly(2-ethyl cyanoacrylate) (PECA), an FDA-approved polymer. Motors
      were fabricated in two different length scales, 3 cm and 300 MUm. The motion of
      the motors is induced by self-generated surface tension gradients along their
      bodies. The motors are capable of moving in various media, including salt
      solutions and artificial serum. 

PMID- 24094035
TI  - Tumor diagnosis with new 111In-radioligands based on truncated human gastrin
      releasing peptide sequences: synthesis and preclinical comparison.
AB  - Radiolabeled analogs of the frog tetradecapeptide bombesin (BBN) have been
      proposed for diagnosis and therapy of gastrin releasing peptide receptor (GRPR)
      expressing tumors. Following a different and yet unexplored approach, we have
      developed four novel (111)In-labeled truncated analogs of the human 27-mer GRP
      after conjugation of 1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid
      (DOTA) at the N-terminus of GRP(13/14/17/18-27) fragments. Analog affinities for
      the human GRPR determined against [(125)I-Tyr(4)]BBN were at the nanomolar level
      and dependent on truncation site. The respective (111)In radioligands
      specifically internalized in GRPR-expressing PC-3 cells. The shorter chain
      [(111)In-DOTA]GRP(17/18-27) analogs showed higher metabolic stability in mice.
      Radioligands specifically localized in human PC-3 xenografts in SCID mice, with
      [(111)In-DOTA]GRP(17-27) exhibiting the most favorable pharmacokinetic profile.
      This study has demonstrated the efficacy of human GRP-based radiopeptides to
      target GRPR-positive lesions in vivo and has revealed the impact of GRP chain
      length on key biological parameters of resulting radiotracers. 

PMID- 24094039
TI  - Peer-coaching with health care professionals: what is the current status of the
      literature and what are the key components necessary in peer-coaching? A scoping
      review.
AB  - BACKGROUND: Peer-coaching has been used within the education field to
      successfully transfer a high percentage of knowledge into practice. In recent
      years, within health care, it has been the subject of interest as a method of
      both student training and staff continuing education as well as a format for
      knowledge translation. AIMS: To review the literature from health care training
      and education to determine the nature and use of peer-coaching. METHOD: Due to
      the status of the literature, a scoping review methodology was followed. From a
      total of 137 articles, 16 were found to fit the inclusion criteria and were
      further reviewed. RESULTS: The review highlights the state of the literature
      concerning peer-coaching within health care and discusses key aspects of the peer
      coaching relationship that are necessary for success. CONCLUSIONS: Most research
      is being conducted in the domains of nursing and medicine within North America.
      The number of studies has increased in frequency over the past 10 years. Interest
      in developing the potential of peer-coaching in both health care student
      education and continuing clinical education of health care professionals has
      grown. Future directions for research in this quickly developing area are
      included.

PMID- 24094038
TI  - The branched-chain aminotransferase proteins: novel redox chaperones for protein
      disulfide isomerase--implications in Alzheimer's disease.
AB  - AIMS: The human branched-chain aminotransferase proteins (hBCATm and hBCATc) are
      regulated through oxidation and S-nitrosation. However, it remains unknown
      whether they share common redox characteristics to enzymes such as protein
      disulfide isomerase (PDI) in terms of regulating cellular repair and protein
      misfolding. RESULTS: Here, similar to PDI, the hBCAT proteins showed dithiol
      disulfide isomerase activity that was mediated through an S-glutathionylated
      mechanism. Site-directed mutagenesis of the active thiols of the CXXC motif
      demonstrates that they are fundamental to optimal protein folding. Far Western
      analysis indicated that both hBCAT proteins can associate with PDI. Co
      immunoprecipitation studies demonstrated that hBCATm directly binds to PDI in IMR
      32 cells and the human brain. Electron and confocal microscopy validated the
      expression of PDI in mitochondria (using Mia40 as a mitochondrial control), where
      both PDI and Mia40 were found to be co-localized with hBCATm. Under conditions of
      oxidative stress, this interaction is decreased, suggesting that the proposed
      chaperone role for hBCATm may be perturbed. Moreover, immunohistochemistry
      studies show that PDI and hBCAT are expressed in the same neuronal and
      endothelial cells of the vasculature of the human brain, supporting a
      physiological role for this binding. INNOVATION: This study identifies a novel
      redox role for hBCAT and confirms that hBCATm differentially binds to PDI under
      cellular stress. CONCLUSION: These studies indicate that hBCAT may play a role in
      the stress response of the cell as a novel redox chaperone, which, if
      compromised, may result in protein misfolding, creating aggregates as a key
      feature in neurodegenerative conditions such as Alzheimer's disease.

PMID- 24094040
TI  - Purely in silico BCS classification: science based quality standards for the
      world's drugs.
AB  - BCS classification is a vital tool in the development of both generic and
      innovative drug products. The purpose of this work was to provisionally classify
      the world's top selling oral drugs according to the BCS, using in silico methods.
      Three different in silico methods were examined: the well-established group
      contribution (CLogP) and atom contribution (ALogP) methods, and a new method
      based solely on the molecular formula and element contribution (KLogP).
      Metoprolol was used as the benchmark for the low/high permeability class
      boundary. Solubility was estimated in silico using a thermodynamic equation that
      relies on the partition coefficient and melting point. The validity of each
      method was affirmed by comparison to reference data and literature. We then used
      each method to provisionally classify the orally administered, IR drug products
      found in the WHO Model list of Essential Medicines, and the top-selling oral drug
      products in the United States (US), Great Britain (GB), Spain (ES), Israel (IL),
      Japan (JP), and South Korea (KR). A combined list of 363 drugs was compiled from
      the various lists, and 257 drugs were classified using the different in silico
      permeability methods and literature solubility data, as well as BDDCS
      classification. Lastly, we calculated the solubility values for 185 drugs from
      the combined set using in silico approach. Permeability classification with the
      different in silico methods was correct for 69-72.4% of the 29 reference drugs
      with known human jejunal permeability, and for 84.6-92.9% of the 14 FDA reference
      drugs in the set. The correlations (r(2)) between experimental log P values of
      154 drugs and their CLogP, ALogP and KLogP were 0.97, 0.82 and 0.71,
      respectively. The different in silico permeability methods produced comparable
      results: 30-34% of the US, GB, ES and IL top selling drugs were class 1, 27-36.4%
      were class 2, 22-25.5% were class 3, and 5.46-14% were class 4 drugs, while ~8%
      could not be classified. The WHO list included significantly less class 1 and
      more class 3 drugs in comparison to the countries' lists, probably due to
      differences in commonly used drugs in developing vs industrial countries. BDDCS
      classified more drugs as class 1 compared to in silico BCS, likely due to the
      more lax benchmark for metabolism (70%), in comparison to the strict permeability
      benchmark (metoprolol). For 185 out of the 363 drugs, in silico solubility values
      were calculated, and successfully matched the literature solubility data. In
      conclusion, relatively simple in silico methods can be used to estimate both
      permeability and solubility. While CLogP produced the best correlation to
      experimental values, even KLogP, the most simplified in silico method that is
      based on molecular formula with no knowledge of molecular structure, produced
      comparable BCS classification to the sophisticated methods. This KLogP, when
      combined with a mean melting point and estimated dose, can be used to
      provisionally classify potential drugs from just molecular formula, even before
      synthesis. 49-59% of the world's top-selling drugs are highly soluble (class 1
      and class 3), and are therefore candidates for waivers of in vivo bioequivalence
      studies. For these drugs, the replacement of expensive human studies with
      affordable in vitro dissolution tests would ensure their bioequivalence, and
      encourage the development and availability of generic drug products in both
      industrial and developing countries. 

PMID- 24094041
TI  - Spine Day 2012: spinal pain in Swiss school children- epidemiology and risk
      factors.
AB  - BACKGROUND: The key to a better understanding of the immense problem of spinal
      pain seems to be to investigate its development in adolescents. Based on the data
      of Spine Day 2012 (an annual action day where Swiss school children were examined
      by chiropractors on a voluntary basis for back problems), the aim of the present
      study was to gain systematic epidemiologic data on adolescent spinal pain in
      Switzerland and to explore risk factors per gender and per spinal area. METHOD:
      Data (questionnaires and physical examinations) of 836 school children were
      descriptively analyzed for prevalence, recurrence and severity of spinal pain. Of
      those, 434 data sets were included in risk factor analysis. Using logistic
      regression analysis, psycho-social parameters (presence of parental back pain,
      parental smoking, media consumption, type of school bag) and physical parameters
      (trunk symmetry, posture, mobility, coordination, BMI) were analyzed per gender
      and per spinal area. RESULTS: Prevalence of spinal pain was higher for female
      gender in all areas apart from the neck. With age, a steep increase in prevalence
      was observed for low back pain (LBP) and for multiple pain sites. The increasing
      impact of spinal pain on quality of life with age was reflected in an increase in
      recurrence, but not in severity of spinal pain. Besides age and gender, parental
      back pain (Odds ratio (OR)=3.26, p=0.011) and trunk asymmetry (OR=3.36, p=0.027)
      emerged as risk factors for spinal pain in girls. Parental smoking seemed to
      increase the risk for both genders (boys: OR=2.39, p=0.020; girls: OR=2.19,
      p=0.051). Risk factor analysis per spinal area resulted in trunk asymmetry as
      risk factor for LBP (OR=3.15, p=0.015), while parental smoking increased the risk
      for thoracic spinal pain (TSP) (OR=2.83, p=0.036) and neck pain (OR=2.23,
      p=0.038). The risk for TSP was further enhanced by a higher BMI (OR=1.15,
      p=0.027). CONCLUSION: This study supports the view of adolescent spinal pain as a
      bio-psycho-social problem that should be investigated per spinal area, age and
      gender. The role of trunk asymmetry and passive smoking as risk factors as well
      as the association between BMI and TSP should be further investigated, preferably
      in prospective studies.

PMID- 24094042
TI  - Subcutaneous emphysema as the first relevant clinical sign of complicated
      tubercular lymph node disease in a child.
AB  - BACKGROUND: Children make up a significant proportion of the global tuberculosis
      (TB) caseload, and experience considerable TB-related morbidity and mortality.
      Unfortunately, it is not easy to diagnose TB in the first years of life because
      of the diversity of its clinical presentation and the non-specific nature of most
      of its symptoms. CASE PRESENTATION: A 26-month-old male child was admitted to
      hospital because of the sudden onset of rapidly increasing swelling of the neck,
      face and upper trunk a few hours before. Upon admission, his temperature was 36.5
      degrees C, pulse rate 120/min, respiratory rate 36/min, and O2 saturation 97% in
      air. Palpation revealed subcutaneous emphysema (SE) over the swollen skin areas,
      and an examination of the respiratory system revealed crepitations in the left
      part of the chest without any significant suggestion of mediastinal shift. Chest
      radiography showed enlargement of the left lung hilum with pneumomediastinum and
      diffuse SE. Bronchoscopy was carried out because of the suspicion that the SE may
      have been due to the inhalation of a peanut. This excluded the presence of a
      foreign body but showed that the left main bronchus was partially obstructed with
      caseous material and showed significant signs of granulomatous inflammation on
      the wall. Contrast-enhanced computed tomography of the lungs confirmed the SE and
      pneumomediastinum, and revealed bilateral hilum lymph node disease with
      infiltration of the adjacent anatomical structure and a considerable breach in
      the left primary bronchus wall conditioning the passage of air in the mediastinum
      and subcutaneous tissue. As a tuberculin skin test and polymerase chain reaction
      for Mycobacterium tuberculosis on bronchial material and gastric aspirate were
      positive, a diagnosis of TB was made and oral anti-TB therapy was started, which
      led to the elimination of M. tuberculosis and a positive clinical outcome.
      CONCLUSIONS: This is the first case in which SE was the first relevant clinical
      manifestation of TB and arose from infiltration of the bronchial wall secondary
      to caseous necrosis of the hilum lymph nodes. Physicians should be aware of the
      fact that SE is one of the possible initial signs and symptoms of early TB
      infection, and act accordingly.

PMID- 24094043
TI  - Ultrasound evaluation of common carotid artery blood flow in the Labrador
      retriever.
AB  - BACKGROUND: Doppler ultrasound (DUS) examination provides quantitative and
      qualitative information concerning the blood flow in veins and arteries, enabling
      their morphological evaluation and the collection of hemodynamic data. Dogs and
      cats as well as humans may display neurological signs of brain hypoperfusion
      secondary to common carotid alterations. Hence, DUS examination might aid in the
      differential diagnosis of neurological disorders of ischemic origin, among other
      causes. The objective of this study was to register normal values for systolic
      peak velocity, minimum diastolic velocity, diameter and resistance index of both
      common carotid arteries of 12 healthy Labrador retriever dogs between 2 and 5
      years of age. By gathering these values, we might be able to improve the
      sensitivity of hemodynamic studies in clinically important brain disorders.
      RESULTS: There were no statistical differences between the values for the right
      and left vessels: the systolic peak velocity was 75.8 +/- 16 cm/s, minimum
      diastolic velocity was 12.2 +/- 4 cm/s, common carotid diameter was 0.545 +/-
      0.063 cm, and resistance index was 0.83 +/- 0.07. CONCLUSIONS: The results of
      this study might be used to establish normal parameters for Labrador retriever
      dogs and thus help in the diagnosis of neurological disorders associated with
      alterations of the carotid arteries. Similar studies must be performed to
      evaluate the same parameters in other dog breeds of different sizes and skull
      conformations.

PMID- 24094044
TI  - Potentiometric sensors with carbon black supporting platinum nanoparticles.
AB  - For the first time, a single-piece, all-solid-state ion-selective electrode was
      fabricated with carbon black supporting platinum nanoparticles (PtNPs-CB) and a
      polymeric membrane. The PtNPs-CB, as an intermediate layer, was drop-casted
      directly on the solid substrate, and then an ionophore-doped solvent polymeric
      membrane was added in order to form a sensor. The performance of the newly
      developed electrodes was evaluated on the basis of potassium and nitrate ions.
      The stability of the electrical potential for the electrodes was examined by
      performing current-reversal chronopotentiometry, and the influence of the
      interfacial water film was assessed by the potentiometric aqueous-layer test.
      Fabricated potassium- and nitrate-selective electrodes displayed a Nernstian
      slope and several outstanding properties such as high long-term potential
      stability, potential repeatability, and reproducibility. 

PMID- 24094045
TI  - Myelodysplastic syndromes: toward a risk-adapted treatment approach.
AB  - Several classification and scoring systems have been developed in myelodysplastic
      syndromes (MDS to predict the risk of progression to acute myeloid leukemia and
      survival. These prognostication models have been also used to inform therapeutic
      decision-making in a risk-adapted fashion. Patient-related factors such as age,
      comorbidities, and functional status have to be considered as well. Here we
      review a risk-guided therapeutic approach for the management of MDS patients. It
      is anticipated that the improved understanding of the complex pathogenesis of MDS
      and the recent discovery of important molecular lesions will be translated into
      novel therapeutic approaches. Additionally, some prognostic aberrations are
      expected to be incorporated into the prognostic tools with the goal of improving
      their prognostic precision and therefore allow for a more informed therapeutic
      decision-making based on the individual's risk profile. 

PMID- 24094046
TI  - In pursuit of a valid Information Assessment Method for continuing education: a
      mixed methods study.
AB  - BACKGROUND: The Information Assessment Method (IAM) is a popular tool for
      continuing education and knowledge translation. After a search for information,
      the IAM allows the health professional to report what was the search objective,
      its cognitive impact, as well as any use and patient health benefit associated
      with the retrieved health information. In continuing education programs,
      professionals read health information, rate it using the IAM, and earn continuing
      education credit for this brief individual reflective learning activity. IAM
      items have been iteratively developed using literature reviews and qualitative
      studies. Thus, our research question was: what is the content validity of IAM
      items from the users' perspective? METHODS: A two-step content validation study
      was conducted. In Step 1, we followed a mixed methods research design, and
      assessed the relevance and representativeness of IAM items. In this step, data
      from a longitudinal quantitative study and a qualitative multiple case study
      involving 40 family physicians were analyzed. In Step 2, IAM items were analyzed
      and modified based on a set of guiding principles by a multi-disciplinary expert
      panel. RESULTS: The content validity of 16 IAM items was supported, and these
      items were not changed. Nine other items were modified. Three new items were
      added, including two that were extensions of an existing item. CONCLUSION: A
      content validated version of the IAM (IAM 2011) is available for the continuing
      education of health professionals.

PMID- 24094047
TI  - Novel oxytocin receptor agonists and antagonists: a patent review (2002 - 2013).
AB  - INTRODUCTION: Oxytocin is a nine amino acid cyclic peptide hormone with a high
      degree of uterotonic activity. The oxytocin receptor (Oxtr) is most strongly
      expressed in the uterus and mammary gland, but can also be found in regions of
      the brain, showing a neurotransmitter-like activity. The Oxtr knockout mice have
      no obvious defects in fertility or sexual behavior, but display aberrant social
      behavior. All of these suggest that Oxtr may become an important therapeutic
      target for the treatment of a wide range of conditions. AREAS COVERED: This
      article will highlight the significant progress that has been made in the
      discovery and development of Oxtr agonists and antagonists in the patent
      literature between January 2002 and May 2013. EXPERT OPINION: In the past decade,
      cumulative evidence supports the idea that activation of the Oxtr can have a
      positive effect upon human cognition and social behavior. The authors suggest
      that new agonists and antagonists may play an important role in the treatment of
      disorders such as anxiety, autism or schizophrenia. It may even be that older
      Oxtr agonists and antagonists, which were used to overcome labor-related
      dysfunction, may also have a significant impact on human social behavior.

PMID- 24094049
TI  - Quantifying key parameters as elicitors for alternate fruit bearing in cv.
      'Elstar' apple trees.
AB  - The commonly known alternate bearing, i.e. year-to-year change of large and small
      yields of fruit tree crops worldwide, is often induced by abiotic stress such as
      late frost, which will eliminate flowers or fruitlets. This study presents an
      alternative form, biotic biennial bearing, i.e. change of large and small yields
      of the same trees within the same tree row in the same year. Three methods were
      developed or modified for the analysis of the number of flower clusters and yield
      of 2086 apple (Malus domestica Borkh.) cv. 'Elstar' trees. The first method,
      i.e., based on intersect between yield in year x and year x+1 and flower clusters
      in year x, yielded 91-106 flower clusters, whereas the second method, i.e., mean
      yield in year x and year x+1, resulted in a range of 72-133 flower clusters, or
      9.6kg/tree necessary for sustainable cultivation of apple cv. 'Elstar'. The third
      'biennial bearing index' (BBI), was calculated in three ways as the ratio of
      differences in tree yields to cumulative tree yield, for individual trees (rather
      than orchard average) to demonstrate the tree-to-tree alternation. A scheme for
      the possible underlying regulatory mechanisms was developed, which includes
      potential elicitors such as light deprivation and subsequent lack of flower
      initiation, are discussed as a possible result of polar basipetal GA7 transport,
      cytokinin level in the xylem and phloem and down-regulation of the gene
      expression of the flowering gene. Suggested countermeasures included early
      chemical or mechanical thinning. 

PMID- 24094048
TI  - MlWRKY12, a novel Miscanthus transcription factor, participates in pith secondary
      cell wall formation and promotes flowering.
AB  - WRKY proteins play crucial roles in various plant processes. An AtWRKY12
      homologous gene, named MlWRKY12, was isolated from Miscanthus lutarioriparius.
      The MlWRKY12 gene encodes a WRKY transcription factor belonging to the group IIc
      subfamily. MlWRKY12 is a nuclear protein. Gene expression pattern analysis
      revealed a relatively high MlWRKY12 expression level in rhizomes, stems and leaf
      sheaths. In situ hybridization analysis further demonstrated that MlWRKY12 was
      expressed in vascular bundle sheath, sclerenchyma and parenchyma tissues. The
      heterologous expression of MlWRKY12 in an atwrky12 background mutant successfully
      rescued the phenotype of pith cell walls caused by the defect of AtWRKY12. Most
      strikingly, the transgenic Arabidopsis plants overexpressing MlWRKY12 exhibited
      early flowering. The transcript abundance of flowering related genes was measured
      by quantitative RT-PCR analysis, suggesting that overexpression of MlWRKY12 in
      Arabidopsis had a significant impact on the expression level of CONSTANS (CO).
      Moreover, the expression levels of FLOWERING LOCUS T (FT), LFY (LEAFY), APETALA1
      (AP1), CAULIFLOWER (CAL) and FRUITFULL (FUL) were upregulated in transgenic
      plants. These results demonstrated the conserved function of MlWRKY12 existing in
      secondary cell wall formation of monocotyledonous species and implied a possible
      impact of MlWRKY12 on flowering control. 

PMID- 24094050
TI  - Do toxic ions induce hormesis in plants?
AB  - The concept of hormesis in plants is critically reviewed, taking growth
      stimulation by low concentrations of toxic trace elements as a reference. The
      importance of both non-adaptive and adaptive mechanisms underlying ion-induced
      hormetic growth responses is highlighted. The activation of defense mechanisms by
      metal ions and pathogenic elicitors and the cross talk between the signals
      induced by metal ions and biotic stressors are considered. The production of
      reactive oxygen species and, consequently, the induction of stress-induced
      antioxidants, are key mechanisms in metal ion-induced hormesis in plants. It is
      concluded that in the current scientific literature, hormesis is used as an
      "umbrella" term that includes a wide range of different mechanisms. It is
      recommended that the term hormesis be used in plant toxicology as a descriptive
      term for the stimulated phase in growth response curves that is induced by low
      concentrations of toxic metal ions without evidence of the underlying mechanisms.
      If the mechanisms underlying the stimulated growth phase have been identified,
      specific terms, such as amelioration, defense gene activation, priming or
      acclimation, should be used. 

PMID- 24094051
TI  - Transcriptomics of induced defense responses to greenbug aphid feeding in near
      isogenic wheat lines.
AB  - The greenbug aphid, Schizaphis graminum (Rondani) is an important cereal pest,
      periodically threatening wheat yields in the United States and around the world.
      The single dominant gene, Gb3-based resistance is highly durable against
      prevailing greenbug biotypes under field conditions; however, the molecular
      mechanisms of Gb3-mediated defense responses remain unknown. We used Affymetrix
      GeneChip Wheat Genome Arrays to investigate the transcriptomics of host defense
      responses upon greenbug feeding on resistant and susceptible bulks (RB and SB,
      respectively) derived from two near-isogenic lines. The study identified 692
      differentially expressed transcripts and further functional classification
      recognized 122 transcripts that are putatively associated to mediate biotic
      stress responses. In RB, Gb3-mediated resistance resulted in activation of
      transmembrane receptor kinases and signaling-related transcripts involved in
      early signal transduction cascades. While in SB, transcripts mediating final
      steps in jasmonic acid biosynthesis, redox homeostasis, peroxidases, glutathione
      S-transferases, and notable defense-related secondary metabolites were induced.
      Also transcripts involved in callose and cell wall decomposition were elevated
      SB, plausibly to facilitate uninterrupted feeding operations. These results
      suggest that Gb3-mediated resistance is less vulnerable to cell wall modification
      and the data provides ample tools for further investigations concerning R gene
      based model of resistance. 

PMID- 24094053
TI  - Isolation of an alcohol dehydrogenase cDNA from and characterization of its
      expression in chrysanthemum under waterlogging.
AB  - A PCR strategy was used to isolate a full-length CgADH (alcohol dehydrogenase)
      cDNA from chrysanthemum. The gene putatively encodes a 378 residue polypeptides,
      which shares 95% homology with tomato alcohol dehydrogenase class III. Endogenous
      ethylene generated in waterlogged Chrysanthemum zawadskii was enhanced by
      exogenous ethylene but decreased by 1-methylcyclopropene (1-MCP), an inhibitor of
      ethylene action. In waterlogged roots, the transcription of the gene encoding
      alcohol dehydrogenase (ADH, EC 1.1.1.1) increased rapidly but transiently,
      peaking at 7.5 fold the non-waterlogged level after 2h of stress. Waterlogging
      elevated ADH activity after a prolonged episode of stress. The exogenous supply
      of 40MULL(-1) ethylene suppressed the production of ethanol, while that of 4MULL(
      1) 1-MCP enhanced it. Ethylene appeared to suppress an acceleration of both CgADH
      expression and fermentation, and alleviates ethanolic fermentation probably
      through by as a signal to acceleration of waterlogging-induced aerenchyma
      formation. This supports the previously observed phenomenon that the expression
      level of ADH gene is regulated by the local level of physiologically active
      ethylene. The relevance of the CgADH gene in relation to chrysanthemum
      waterlogging was discussed as well. 

PMID- 24094052
TI  - Peroxidation due to cryoprotectant treatment is a vital factor for cell survival
      in Arabidopsis cryopreservation.
AB  - Cryopreservation can be a safe and cost-effective tool for the long-term storage
      of plant germplasm. In Arabidopsis, the ability to recover from cryogenic
      treatment was lost as growth progressed. Growth could be restored in 48-h
      seedlings, whereas 72-h seedlings died after cryogenic treatment. Why seedling
      age and survival are negatively correlated is an interesting issue. A comparative
      transcriptomics was performed to screen differentially expressed genes between 48
      and 72-h seedlings after exposure to cryoprotectant. Among differentially
      expressed genes, oxidative stress response genes played important roles in
      cryoprotectant treatment, and peroxidation was a key factor related to cell
      survival. Seedlings underwent more peroxidation at 72-h than at 48-h. A
      comprehensive analysis indicated that peroxidation injured membrane systems
      leading to photophosphorylation and oxidative phosphorylation damage.
      Furthermore, the apoptosis-like events were found in cryogenic treatment of
      Arabidopsis seedlings. 48- and 72-h seedlings underwent different degrees of
      membrane lipid peroxidation during cryoprotectant treatment, and reducing the
      injury of oxidative stress was an important factor to successful
      cryopreservation. This study provided a novel insight of genetic regulatory
      mechanisms in cryopreservation, and established an excellent model to test and
      evaluate the effect of exogenous antioxidants and conventional cryoprotectants in
      plant cryopreservation. 

PMID- 24094054
TI  - Enzymatic transamination of pyridoxamine in tobacco plants.
AB  - Vitamin B6 (VB6) comprises a group of pyridine compounds that are involved in a
      surprisingly high diversity of biochemical reactions. Humans and animals depend
      largely on plants for their VB6 nutrition. Many studies have focused on
      biosynthesis of VB6 and comparatively little is known about VB6 metabolic
      conversion in plants. Recently, we have found that an efficient conversion
      pathway between pyridoxal (PL) and pyridoxamine (PM) is present in tobacco, but
      the catalytic enzyme remains an unsolved mystery. In this study, enzymes
      catalyzing the transamination of PM were purified from tobacco leaves and
      characterized. Our results suggest that a specific PM-pyruvate aminotranferase
      dominates the reversible transamination of PM in tobacco, and also show that the
      apo form of glutamic-oxaloacetic aminotranferase from tobacco, but not the
      holoenzyme, is able to catalyze the analogous transamination reaction between PM
      and either oxaloacetate or alpha-ketoglutarate. PM-pyruvate aminotranferase is
      involved in a degradation pathway for VB6 compounds in bacteria. Therefore, our
      study raises questions about whether the degradation pathway of VB6 exists in
      plants. 

PMID- 24094055
TI  - Strategies and future trends to identify the mode of action of phytotoxic
      compounds.
AB  - Small molecules affecting plant processes have been widely used as probes to
      study basic physiology. In agricultural practices some of these molecules have
      served as herbicides or plant growth regulators. Historically, most of the
      compounds were identified in large screens by the agrochemical industry, but also
      as phytoactive natural products. More recently, novel phytoactive compounds
      originated from academic research by chemical screens performed to induce
      specific phenotypes of interest. In the present review different approaches were
      evaluated for the identification of the mode of action (MoA) of phytoactive
      compounds. Based on the methodologies used for MoA identification, three
      approaches are differentiated: a phenotyping approach, an approach based on a
      genetic screen and a biochemical screening approach. Target sites of compounds
      targeting primary or secondary metabolism were identified most successfully with
      a phenotyping approach. Target sites for compounds that influence cell structure,
      such as cell wall biosynthesis or the cytoskeleton, or compounds that interact
      with the hormone system, were in most cases discovered by using a genetic
      approach. Examples showing the strengths and weaknesses of the different
      approaches are discussed in detail. Additionally, new techniques that could
      contribute to future MoA identification projects are reviewed. In particular,
      next-generation sequencing techniques may be used for the fast-forward mapping of
      mutants identified in genetic screens. Finally, a revised three-tiered approach
      for the MoA identification of phytoactive compounds is proposed. The approach
      consists of a 1st tier, which addresses compound stability, uniformity of effects
      in different species, general cytotoxicity and the effect on common processes
      such as transcription and translation. Advanced studies based on these findings
      initiate the 2nd tier MoA characterization, either with further phenotypic
      characterization, starting a genetic screen or establishing a biochemical screen.
      At the 3rd tier, enzyme assays or protein affinity studies should show the
      activity of the compound on the hypothesized target and should associate the in
      vitro effects with the in vivo profile of the compound. 

PMID- 24094056
TI  - Potential transgenic routes to increase tree biomass.
AB  - Biomass is a prime target for genetic engineering in forestry because increased
      biomass yield will benefit most downstream applications such as timber, fiber,
      pulp, paper, and bioenergy production. Transgenesis can increase biomass by
      improving resource acquisition and product utilization and by enhancing
      competitive ability for solar energy, water, and mineral nutrients. Transgenes
      that affect juvenility, winter dormancy, and flowering have been shown to
      influence biomass as well. Transgenic approaches have increased yield potential
      by mitigating the adverse effects of prevailing stress factors in the
      environment. Simultaneous introduction of multiple genes for resistance to
      various stress factors into trees may help forest trees cope with multiple or
      changing environments. We propose multi-trait engineering for tree crops,
      simultaneously deploying multiple independent genes to address a set of
      genetically uncorrelated traits that are important for crop improvement. This
      strategy increases the probability of unpredictable (synergistic or detrimental)
      interactions that may substantially affect the overall phenotype and its long
      term performance. The very limited ability to predict the physiological processes
      that may be impacted by such a strategy requires vigilance and care during
      implementation. Hence, we recommend close monitoring of the resultant transgenic
      genotypes in multi-year, multi-location field trials. 

PMID- 24094057
TI  - Review of stress specific organelles-to-nucleus metabolic signal molecules in
      plants.
AB  - Plants, as sessile organisms, have evolved an exquisitely tuned response network
      to survive environmental perturbations. Organelles-to-nucleus signaling, termed
      retrograde signaling, plays a key role in stress responses by communicating
      subcellular perturbations to the nucleus, thereby coordinating expression of
      stress specific nuclear genes essential for adaptive responses to hostile
      environment. Recently, several stress specific retrograde signals have been
      identified; most notable amongst them are reactive oxygen species, tetrapyrroles,
      2-C-methyl-d-erythritol 2,4-cyclodiphosphate (MEcPP), unsaturated fatty acids,
      nitric oxide (NO), 3'-phosphoadenosine 5'-phosphate (PAP), and beta-cyclocitral
      (beta-CC). It is expected that this trend will continue to provide fundamental
      insight into the integrative network of sensory systems central to the adaptive
      responses of plants to the prevailing environment. This review focuses on the
      recent advancements in the field. 

PMID- 24094058
TI  - Development of the gas puff charge exchange recombination spectroscopy (GP-CXRS)
      technique for ion measurements in the plasma edge.
AB  - A novel charge-exchange recombination spectroscopy (CXRS) diagnostic method is
      presented, which uses a simple thermal gas puff for its donor neutral source,
      instead of the typical high-energy neutral beam. This diagnostic, named gas puff
      CXRS (GP-CXRS), is used to measure ion density, velocity, and temperature in the
      tokamak edge/pedestal region with excellent signal-background ratios, and has a
      number of advantages to conventional beam-based CXRS systems. Here we develop the
      physics basis for GP-CXRS, including the neutral transport, the charge-exchange
      process at low energies, and effects of energy-dependent rate coefficients on the
      measurements. The GP-CXRS hardware setup is described on two separate tokamaks,
      Alcator C-Mod and ASDEX Upgrade. Measured spectra and profiles are also
      presented. Profile comparisons of GP-CXRS and a beam based CXRS system show good
      agreement. Emphasis is given throughout to describing guiding principles for
      users interested in applying the GP-CXRS diagnostic technique. 

PMID- 24094059
TI  - Unusual increase in reported cases of paratyphoid A fever among travellers
      returning from Cambodia, January to September 2013.
AB  - From January to September 2013, a marked increase in notifications of Salmonella
      Paratyphi A infections among travellers returning from Cambodia occurred in
      France. An investigation revealed 35 cases without a common source: 21 in France,
      five in Germany, three in the Netherlands, one in Norway, one in the United
      Kingdom, four in New-Zealand. Data suggest an ongoing event that should trigger
      further investigation. Travellers to Cambodia should observe preventive measures
      including good personal hygiene and food handling practices.

PMID- 24094060
TI  - Increase in Salmonella enterica serovar Paratyphi A infections in Phnom Penh,
      Cambodia, January 2011 to August 2013.
AB  - We report an increased number of Salmonella enterica Paratyphi A infections in
      adults in Cambodia. Between January 2011 and August 2013, 71 S. Paratyphi A
      isolates were recovered from blood cultures, representing a 44-fold increase
      compared to July 2007 to December 2010, while monthly numbers of cultures did not
      change. Infections with S. Typhi increased two-fold in the same period. Most
      cases came from the capital Phnom Penh. These findings warrant epidemiological
      investigation to support public health measures.

PMID- 24094061
TI  - Taking stock of the first 133 MERS coronavirus cases globally--Is the epidemic
      changing?
AB  - Since June 2012, 133 Middle East respiratory syndrome coronavirus (MERS-CoV)
      cases have been identified in nine countries. Two time periods in 2013 were
      compared to identify changes in the epidemiology. The case-fatality risk (CFR) is
      45% and is decreasing. Men have a higher CFR (52%) and are over-represented among
      cases. Thirteen out of 14 known primary cases died. The sex-ratio is more
      balanced in the latter period. Nosocomial transmission was implied in 26% of the
      cases.

PMID- 24094062
TI  - High uptake of HPV immunisation in Scotland--perspectives on maximising uptake.
AB  - In September 2008, Scotland introduced a national human papillomavirus (HPV)
      immunisation programme with bivalent HPV vaccine, to prevent cervical cancer.
      This school-based programme routinely vaccinates girls aged between 12 and 13
      years. A catch-up campaign, running over three years, also began at this time,
      offering vaccination to all girls aged 13 years to under 18 years old. The HPV
      immunisation campaign presented challenges due to this vaccine being targeted to
      girls in school and older girls who had left school. Following a long and
      comprehensive planning process, this campaign was successfully implemented across
      Scotland, delivering high vaccine uptake of 91.4% for three doses of vaccine in
      the first year (September 2008 to August 2009) for the routine cohort and 90.1%
      in the second year (September 2009 to August 2010) for the routine cohort. We
      describe the planning process, challenges and implementation strategies employed
      to achieve this high uptake.

PMID- 24094064
TI  - Uncovering the geroprotective potential of medicinal plants from the Judea region
      of Israel.
AB  - Plants growing in the Judea region are widely used in traditional medicine. This
      phytogeographic zone stands out in its climatic conditions and biodiversity.
      Consequently, both endemic and widely distributed Mediterranean plants growing in
      the area have unique chemotypes characterized by accumulation of relatively high
      levels of phytosteroids. Our comprehensive analysis revealed that many of the
      plants growing in the Judea region may hold a geroprotective potential. With this
      in mind, we undertook a wide screen of dozens of candidate herbal extracts for
      their cell protective, wound-healing, anti-inflammatory, and anti-cancer
      activities. The results obtained thus far have clearly shown that the extracts
      tested (1) protect normal human fibroblasts from genotoxic stress (prevent DNA
      double-strand beaks, increase cell survival and reduce the number of cells
      undergoing cellular senescence), (2) decrease secretion of pro-inflammatory
      cytokines, (3) promote wound healing, and (4) exert more pronounced cytotoxicity
      toward cancer cells.

PMID- 24094065
TI  - Computational study of the Fe(CN)2CO cofactor and its binding to HypC protein.
AB  - In the intricate maturation process of [NiFe]-hydrogenases, the Fe(CN)2CO
      cofactor is first assembled in a HypCD complex with iron coordinated by cysteines
      from both proteins and CO is added after ligation of cyanides. The small
      accessory protein HypC is known to play a role in delivering the cofactor needed
      for assembling the hydrogenase active site. However, the chemical nature of the
      Fe(CN)2CO moiety and the stability of the cofactor-HypC complex are open
      questions. In this work, we address geometries, properties, and the nature of
      bonding of all chemical species involved in formation and binding of the cofactor
      by means of quantum calculations. We also study the influence of environmental
      effects and binding to cysteines on vibrational frequencies of stretching modes
      of CO and CN used to detect the presence of Fe(CN)2CO. Carbon monoxide is found
      to be much more sensitive to sulfur binding and the polarity of the medium than
      cyanides. The stability of the HypC-cofactor complex is analyzed by means of
      molecular dynamics simulation of cofactor-free and cofactor-bound forms of HypC.
      The results show that HypC is stable enough to carry the cofactor, but since its
      binding cysteine is located at the N-terminal unstructured tail, it presents
      large motions in solution, which suggests the need for a guiding interaction to
      achieve delivery of the cofactor. 

PMID- 24094066
TI  - Pharmacology in China: a brief overview.

PMID- 24094067
TI  - Down-regulation of hypothalamic pro-opiomelanocortin (POMC) expression after
      weaning is associated with hyperphagia-induced obesity in JCR rats overexpressing
      neuropeptide Y.
AB  - We hypothesised that hypothalamic feeding-related neuropeptides are
      differentially expressed in obese-prone and lean-prone rats and trigger
      overeating-induced obesity. To test this hypothesis, in the present study, we
      measured energy balance and hypothalamic neuropeptide Y (NPY) and pro
      opiomelanocortin (POMC) mRNA expressions in male JCR:LA-cp rats. We compared, in
      independent cohorts, free-feeding obese-prone (Obese-FF) and lean-prone (Lean-FF)
      rats at pre-weaning (10 d old), weaning (21-25 d old) and early adulthood (8-12
      weeks). A group of Obese-pair-feeding (PF) rats pair-fed to the Lean-FF rats was
      included in the adult cohort. The body weights of 10-d-old Obese-FF and Lean-FF
      pups were not significantly different. However, when the pups were shifted from
      dams' milk to solid food (weaning), the obese-prone rats exhibited more energy
      intake over the days than the lean-prone rats and higher body and fat pad weights
      and fasting plasma glucose, leptin, insulin and lipid levels. These differences
      were consistent with higher energy consumption and lower energy expenditure. In
      the young adult cohort, the differences between the Obese-FF and Lean-FF rats
      became more pronounced, yielding significant age effects on most of the
      parameters of the metabolic syndrome, which were reduced in the Obese-PF rats.
      The obese-prone rats displayed higher NPY expression than the lean-prone rats at
      pre-weaning and weaning, and the expression levels did not differ by age. In
      contrast, POMC expression exhibited significant age-by-genotype differences. At
      pre-weaning, there was no genotype difference in POMC expression, but in the
      weanling cohort, obese-prone pups exhibited lower POMC expression than the lean
      prone rats. This genotype difference became more pronounced at adulthood.
      Overall, the development of hyperphagia-induced obesity in obese-prone JCR rats
      is related to POMC expression down-regulation in the presence of established NPY
      overexpression.

PMID- 24094068
TI  - A computational model for overcoming drug resistance using selective dual
      inhibitors for aurora kinase A and its T217D variant.
AB  - The human Aurora kinase-A (AK-A) is an essential mitotic regulator that is
      frequently overexpressed in several cancers. The recent development of several
      novel AK-A inhibitors has been driven by the well-established association of this
      target with cancer development and progression. However, resistance and cross
      reactivity with similar kinases demands an improvement in our understanding of
      key molecular interactions between the Aurora kinase-A substrate binding pocket
      and potential inhibitors. Here, we describe the implementation of state-of-the
      art virtual screening techniques to discover a novel set of Aurora kinase-A
      ligands that are predicted to strongly bind not only to the wild type protein,
      but also to the T217D mutation that exhibits resistance to existing inhibitors.
      Furthermore, a subset of these computationally screened ligands was shown to be
      more selective toward the mutant variant over the wild type protein. The
      description of these selective subsets of ligands provides a unique
      pharmacological tool for the design of new drug regimens aimed at overcoming both
      kinase cross-reactivity and drug resistance associated with the Aurora kinase-A
      T217D mutation. 

PMID- 24094069
TI  - Gene expression changes leading extreme alkaline tolerance in Amur ide (Leuciscus
      waleckii) inhabiting soda lake.
AB  - BACKGROUND: Amur ide (Leuciscus waleckii) is an economically and ecologically
      important cyprinid species in Northern Asia. The Dali Nor population living in
      the soda lake Dali Nor can adapt the extremely high alkalinity, providing us a
      valuable material to understand the adaptation mechanism against extreme
      environmental stress in teleost. RESULTS: In this study, we generated high
      throughput RNA-Seq data from three tissues gill, liver and kidney of L. waleckii
      living in the soda lake Dali Nor and the fresh water lake Ganggeng Nor, then
      performed parallel comparisons of three tissues. Our results showed that out of
      assembled 64,603 transcript contigs, 28,391 contigs had been assigned with a
      known function, corresponding to 20,371 unique protein accessions. We found 477,
      2,761 and 3,376 differentially expressed genes (DEGs) in the gill, kidney, and
      liver, respectively, of Dali Nor population compared to Ganggeng Nor population
      with FDR <= 0.01 and fold-change >= 2. Further analysis revealed that well-known
      functional categories of genes and signaling pathway, which are associated with
      stress response and extreme environment adaptation, have been significantly
      enriched, including the functional categories of "response to stimulus",
      "transferase activity", "transporter activity" and "oxidoreductase activity", and
      signaling pathways of "mTOR signaling", "EIF2 signaling", "superpathway of
      cholesterol biosynthesis". We also identified significantly DEGs encoding
      important modulators on stress adaptation and tolerance, including carbonic
      anhydrases, heat shock proteins, superoxide dismutase, glutathione S
      transferases, aminopeptidase N, and aminotransferases. CONCLUSIONS: Overall, this
      study demonstrated that transcriptome changes in L. waleckii played a role in
      adaptation to complicated environmental stress in the highly alkalized Dali Nor
      lake. The results set a foundation for further analyses on alkaline-responsive
      candidate genes, which help us understand teleost adaptation under extreme
      environmental stress and ultimately benefit future breeding for alkaline-tolerant
      fish strains.

PMID- 24094071
TI  - Facile fabrication and instant application of miniaturized antibody-decorated
      affinity columns for higher-order structure and functional characterization of
      TRIM21 epitope peptides.
AB  - Both epitope excision and epitope extraction methods, combined with mass
      spectrometry, generate precise informations on binding surfaces of full-length
      proteins, identifying sequential (linear) or assembled (conformational) epitopes,
      respectively. Here, we describe the one-step fabrication and application of
      affinity columns using reversibly immobilized antibodies with highest flexibility
      with respect to antibody sources and lowest sample amount requirements (fmol
      range). Depending on the antibody source, we made use of protein G- or protein A
      coated resins as support materials. These materials are packed in pipet tips and
      in combination with a programmable multichannel pipet form a highly efficient
      epitope mapping system. In addition to epitope identification, the influence of
      epitope structure modifications on antibody binding specificities could be
      studied in detail with synthetic peptides. Elution of epitope peptides was
      optimized such that mass spectrometric analysis was feasible after a single
      desalting step. Epitope peptides were identified by accurate molecular mass
      determinations or by partial amino acid sequence analysis. In addition, charge
      state comparison or ion mobility analysis of eluted epitope peptides enabled
      investigation of higher-order structures. The epitope peptide of the TRIM21
      (TRIM: tripartite motif) autoantigen that is recognized by a polyclonal antibody
      was determined as assembling an "L-E-Q-L" motif on an alpha-helix. Secondary
      structure determination by circular dichroism spectroscopy and structure modeling
      are in accordance with the mass spectrometric results and the antigenic behavior
      of the 17-mer epitope peptide variants from the full-length autoantigen. 

PMID- 24094072
TI  - Radiation exposure from diagnostic procedures following allogeneic stem cell
      transplantation--how much is acceptable?
AB  - BACKGROUND: Frequent diagnostic radiology procedures in allogeneic stem cell
      transplantation (SCT) recipients raise concern about the potential harm from
      incidental radiation. OBJECTIVES: To determine the cumulative radiation dose from
      diagnostic studies in allogeneic SCT and its impact on clinical outcome. PATIENTS
      AND METHODS: This retrospective cohort study was conducted to determine the
      cumulative radiation dose from diagnostic studies following SCT. Sixty-four
      consecutive patients with hematological malignancies in a single tertiary care
      institution underwent total body irradiation (TBI)-based myeloablative
      conditioning followed by six of six human leukocyte antigen (HLA)-identical
      sibling allogeneic SCT. The median follow-up was 3 years. The cumulative
      effective dose in mSv from diagnostic radiological studies in the peri-transplant
      period from day -30 to day +200 was calculated for each patient and its impact on
      overall survival and non-relapse mortality was determined. RESULTS: The median
      cumulative radiation exposure from diagnostic radiological procedures was 92 mSv
      (range 1.2-300), representing about 30* the normal annual background radiation
      for the population and 10% of the 1200 cGy TBI dose used in conditioning. Sixty
      five percent of the cumulative radiation exposure was delivered between day +1
      and day 100 and computed tomography scans contributed 88%. In multivariate
      analysis, diagnostic procedures did not significantly impact clinical outcomes.
      CONCLUSIONS: While radiation exposure from diagnostic procedures did not impact
      clinical outcomes the risk of secondary cancers in long-term survivors is likely
      to be increased. Our results indicate that patients who are acutely ill for
      prolonged periods can receive clinically significant radiation doses during their
      hospital care. Our findings should prompt attempts to limit radiation exposure
      from diagnostic procedures in post-SCT recipients.

PMID- 24094075
TI  - Rho-kinase inhibitors offer a new approach in the treatment of glaucoma.
AB  - INTRODUCTION: Primary open-angle glaucoma (POAG) is a leading cause for worldwide
      blindness and is characterized by progressive optic nerve damage. The etiology of
      POAG is unknown, but elevated intraocular pressure (IOP) and advanced age have
      been identified as risk factors. IOP reduction is the only known treatment for
      glaucoma. Recently, drugs that inhibit rho-associated protein kinase (ROCK) have
      been studied in animals and people for their ability to lower IOP and potentially
      treat POAG. ROCK inhibitors lower IOP through a trabecular mechanism and may
      represent a new therapeutic paradigm for the treatment of POAG. AREAS COVERED:
      Exploring the place that ROCK inhibitors may occupy in our treatment of POAG
      requires a thorough understanding of pathophysiology and treatment. This article
      summarizes current research on the incidence, proposed etiologies and mechanisms
      of action for this drug class. ROCK inhibitor research is presented and
      considered in light of the current standard of pharmacologic care. EXPERT
      OPINION: ROCK inhibitors alter the cell shape and extracellular matrix (ECM) of
      the trabecular meshwork. Preclinical studies demonstrate that these drugs have
      the potential to become a new therapy for glaucoma. However, ROCK inhibitors can
      affect multiple cell types, and their utility can be proven only after clinical
      studies in patients.

PMID- 24094070
TI  - Redox-modulated phenomena and radiation therapy: the central role of superoxide
      dismutases.
AB  - SIGNIFICANCE: Ionizing radiation is a vital component in the oncologist's arsenal
      for the treatment of cancer. Approximately 50% of all cancer patients will
      receive some form of radiation therapy as part of their treatment regimen. DNA is
      considered the major cellular target of ionizing radiation and can be damaged
      directly by radiation or indirectly through reactive oxygen species (ROS) formed
      from the radiolysis of water, enzyme-mediated ROS production, and ROS resulting
      from altered aerobic metabolism. RECENT ADVANCES: ROS are produced as a byproduct
      of oxygen metabolism, and superoxide dismutases (SODs) are the chief scavengers.
      ROS contribute to the radioresponsiveness of normal and tumor tissues, and SODs
      modulate the radioresponsiveness of tissues, thus affecting the efficacy of
      radiotherapy. CRITICAL ISSUES: Despite its prevalent use, radiation therapy
      suffers from certain limitations that diminish its effectiveness, including tumor
      hypoxia and normal tissue damage. Oxygen is important for the stabilization of
      radiation-induced DNA damage, and tumor hypoxia dramatically decreases radiation
      efficacy. Therefore, auxiliary therapies are needed to increase the effectiveness
      of radiation therapy against tumor tissues while minimizing normal tissue injury.
      FUTURE DIRECTIONS: Because of the importance of ROS in the response of normal and
      cancer tissues to ionizing radiation, methods that differentially modulate the
      ROS scavenging ability of cells may prove to be an important method to increase
      the radiation response in cancer tissues and simultaneously mitigate the damaging
      effects of ionizing radiation on normal tissues. Altering the expression or
      activity of SODs may prove valuable in maximizing the overall effectiveness of
      ionizing radiation.

PMID- 24094076
TI  - The usefulness of combined diagnostic CT and (99m)Tc-octreotide somatostatin
      receptor SPECT/CT imaging on pulmonary nodule characterization in patients.
AB  - The objective of this study was to evaluate the clinical value of combination of
      diagnostic computed tomography (CT) and somatostatin receptor imaging with
      (99m)Tc-octreotide acetate SPECT/CT in differentiation of benign pulmonary
      nodules from cancers. METHODS: This was a retrospective study, 29 patients with
      suspected pulmonary neoplasm underwent diagnostic CT and (99m)Tc-octreotide
      SPECT/CT scans, and the tumor-to-normal tissue tracer value (T/N) for (99m)Tc
      octreotide was measured. Diagnosis was confirmed by histological analysis.
      RESULTS: Eighteen of the 29 patients included in this study had lung cancer: 2
      with small cell lung cancer and 16 with nonsmall cell lung cancer. The other 11
      patients had benign lung lesions: 5 with tuberculosis, 4 with nontuberculosis
      infection, 1 with hematoma, and 1 with fibroma. (99m)Tc-octreotide uptake
      (expressed as mean T/N+/-SD) was significantly higher in lung cancers (2.58+/
      0.91) than benign lesions (1.38+/-0.79) (p=0.002). Specificity for pulmonary
      malignant nodule diagnosis was 63.6% for diagnostic CT, 72.7% for somatostatin
      receptor SPECT/CT imaging, and 81.8% for the combined use of diagnostic CT and
      somatostatin receptor SPECT/CT imaging. CONCLUSION: Somatostatin receptor imaging
      with (99m)Tc-octreotide SPECT/CT is useful for the differentiation of benign
      pulmonary nodules from lung cancers, the combination of diagnostic CT and (99m)Tc
      octreotide SPECT/CT further increases the specificity of malignant pulmonary
      nodule detection.

PMID- 24094077
TI  - The effect of probiotics and gut microbiota on Th17 cells.
AB  - Probiotics and gut microbiota have a significant impact on gut homeostasis in the
      host. Recent clinical studies demonstrated the ameliorative features of several
      kinds of probiotics in intestinal disorders, such as inflammatory bowel diseases
      (IBDs). Interleukin (IL)-17 is a potent inflammatory cytokine, and T-helper
      (Th)17 cells and other IL-17-producing cells are involved in the pathogenesis of
      IBD. Multiple mechanisms of action have been suggested to explain the protective
      anti-inflammatory effects of probiotics in intestinal inflammation, including the
      immunoregulation and suppression of Th17 activity and IL-17 production in part by
      signaling through pattern-recognition receptors such as Toll-like receptor
      family. However, steady-state Th17 cells have an important role in host defense
      against fungi and bacteria. Interestingly, recent studies revealed that specific
      commensal bacterial species such as segmented filamentous bacteria (SFB) induce
      the accumulation of Th17 cells in the small intestine in many species, including
      mice. It is important to determine the mechanisms by which intestinal Th17 cells
      are induced by SFB and whether these or other bacteria with similar properties
      are present in the human intestine. This brief review focuses on the interaction
      between probiotics/microbiota and Th17 cells during inflammation (war) and during
      steady-state homeostatic regulation (peace). 

PMID- 24094078
TI  - The feasibility of omitting irradiation to the contralateral lower neck in stage
      N1 nasopharyngeal carcinoma patients.
AB  - PURPOSE: This study was conducted to analyze the feasibility of omitting
      irradiation to the contralateral lower neck in stage N1 nasopharyngeal carcinoma
      (NPC) patients. MATERIALS AND METHODS: From July 2008 to January 2012, 52
      patients with stage N1 NPC were analyzed. All patients were treated with
      intensity-modulated radiation therapy (IMRT) and received bilateral upper neck
      irradiation to levels II, III and VA and ipsilateral lower neck irradiation to
      levels IV and VB. The contralateral lower neck irradiation was omitted. RESULTS:
      The median follow-up was 29 months (range, 12-52 months). The 3-year overall
      survival (OS) rate, progress-free survival (PFS), local failure-free (LFS), nodal
      recurrence-free survival (NFS) and distant metastasis-free survival (DMFS) rates
      were 92.2%, 94.1%, 94.3%, 98% and 94.1%, respectively. Only one patient developed
      a neck recurrence in the irradiation field, while no patients experienced out-of
      field nodal recurrence. Univariate analysis suggested that T classification was
      the only significant prognostic factor for overall survival, and age was
      significantly associated with PFS. Multivariate analyses indicated that age was
      also a predictor for overall survival. The elective neck irradiation procedure
      was not a significant predictor for all of the treatment results. CONCLUSION:
      Selective irradiation to bilateral levels of II, III and VA and unilateral levels
      of IV and VB, omitted the contralateral lower neck in a proportion of patients
      with N1 stage NPC was safe and practicable.

PMID- 24094080
TI  - Hospitalization for diseases attributable to human papillomavirus in the Veneto
      Region (North-East Italy).
AB  - BACKGROUND: Human papillomavirus (HPV) is one of the most common sexually
      transmitted pathogens. A number of studies in the literature have estimated the
      burden of HPV-related diseases by collecting data at primary care level, while a
      comprehensive assessment of the global burden of HPV-related diseases on hospital
      resources is still lacking. METHODS: This was a retrospective cohort study based
      on hospital discharge data collected from 2000 to 2010 in the Veneto Region
      (north-east Italy). All hospitalizations for diseases potentially associated with
      HPV were identified by searching the hospital discharge records, then the
      proportion of these hospitalizations relating to diseases attributable to the HPV
      infection was calculated. RESULTS: Overall, the annual hospitalization rate for
      HPV-related diseases was 21.3 per 100,000 individuals in the general population,
      15.8 per 100,000 males, and 27.6 per 100,000 females. Hospitalizations were due
      mainly to genital warts, and peak among 15- to 44-year-olds in both genders.
      Taking both sexes together, the hospitalizations attributable to HPV dropped from
      24.5/100,000 in 2000 to 17.5/100,000 in 2011, showing a significant decline
      during this period, with an average annual percent change (AAPC) of -1.9% (CI
      95%: -2.8, -0.9;). On the other hand, the hospitalization rate for genital warts
      tended to increase significantly (AAPC 3.0% [CI 95%: 1.4;4.7]), whilst there was
      a significantly declining trend in the hospitalization rate for anal cancer (AAPC
      - 5.0% [CI 95%: -7.7;-2.2]), genital cancer (AAPC -6.2% [CI 95%: -7.8;-4.6]) and
      oropharyngeal cancer (AAPC -4.3% [CI 95%: -4.8;-3,8]). CONCLUSION: Data derived
      from the hospital records indicate that HPV-related diseases are an important
      public health issue.

PMID- 24094079
TI  - RESEARCH (Recognized effect of Statin and ezetimibe therapy for achieving LDL-C
      Goal), a randomized, doctor-oriented, multicenter trial to compare the effects of
      higher-dose statin versus ezetimibe-plus-statin on the serum LDL-C concentration
      of Japanese type-2 diabetes patients design and rationale.
AB  - AIMS: Hypercholesterolemia coexisting with diabetes still requires clinical
      intervention to manage the high risk of cardiovascular disease it poses. No
      second-step strategy is established, however, for cases where strong statins fail
      to bring cholesterol down to target levels. In this study we seek to demonstrate
      the superior effect of ezetimibe in combination with strong statins to reduce LDL
      C in Japanese patients suffering from both T2DM and hyper LDL-cholesterolemia.
      METHODS: T2DM outpatients (109 patients from 16 institutes) who failed to achieve
      the target LDL-C value were recruited and randomly assigned to two groups, a
      double-dose-statin group and ezetimibe-plus-statin group. Follow-ups were
      scheduled at 0, 12, 26, and 52 weeks. The primary endpoint was the percentage
      change in the level of LDL-C from baseline to 12 weeks. INTERIM RESULTS: We could
      successfully create randomized (gender, age, LDL-C, HbA1c, etc.) two groups
      except for slight differences in apolipoprotein-B and sd-LDL. CONCLUSIONS:
      RESEARCH is the first prospective, parallel-group, multicenter study comparing a
      double dose of strong statin with ezetimibe plus strong statin for T2DM patients.
      The RESEARCH study will provide reliable evidence with which to establish a
      clinical strategy for diabetics who fail to achieve the target LDL-C value.

PMID- 24094081
TI  - Mental state deterioration after switching from brand-name to generic olanzapine
      in an adolescent with bipolar affective disorder, autism and intellectual
      disability: a case study.
AB  - BACKGROUND: The appropriateness of use of generic instead of brand-name
      medication remains unresolved and controversial in several areas of medicine.
      Some evidence suggestive of variations in bioavailability and clinical
      effectiveness between different formulations make policy decisions occasionally
      difficult. The use of generic olanzapine is a widely acceptable practice on the
      basis of quality, safety and efficacy data and has been adopted in several
      countries. CASE PRESENTATION: The case of a 14 year old boy with bipolar
      affective disorder, autism and intellectual disability who had brand-name to
      generic olanzapine switch associated with rapid deterioration of his mental state
      is described. This clinical change was not related to any physical illness or
      other medication adjustment and resolved as rapidly when generic olanzapine was
      switched back to the brand-name formulation. CONCLUSIONS: Caution should be
      exercised when policy for switching from brand-name to generic psychotropic
      medications are made, especially when using medications off label, in extremes of
      age and in those patients with co-morbid complicating factors such as
      intellectual disability.

PMID- 24094082
TI  - The value of usability testing for Internet-based adolescent self-management
      interventions: "Managing Hemophilia Online".
AB  - BACKGROUND: As adolescents with hemophilia approach adulthood, they are expected
      to assume responsibility for their disease management. A bilingual (English and
      French) Internet-based self-management program, "Teens Taking Charge: Managing
      Hemophilia Online," was developed to support adolescents with hemophilia in this
      transition. This study explored the usability of the website and resulted in
      refinement of the prototype. METHODS: A purposive sample (n=18; age 13-18; mean
      age 15.5 years) was recruited from two tertiary care centers to assess the
      usability of the program in English and French. Qualitative observations using a
      "think aloud" usability testing method and semi-structured interviews were
      conducted in four iterative cycles, with changes to the prototype made as
      necessary following each cycle. This study was approved by research ethics boards
      at each site. RESULTS: Teens responded positively to the content and appearance
      of the website and felt that it was easy to navigate and understand. The
      multimedia components (videos, animations, quizzes) were felt to enrich the
      experience. Changes to the presentation of content and the website user-interface
      were made after the first, second and third cycles of testing in English. Cycle
      four did not result in any further changes. CONCLUSIONS: Overall, teens found the
      website to be easy to use. Usability testing identified end-user concerns that
      informed improvements to the program. Usability testing is a crucial step in the
      development of Internet-based self-management programs to ensure information is
      delivered in a manner that is accessible and understood by users.

PMID- 24094083
TI  - Antibodies to human angiopoietin-like protein 3: a patent evaluation of
      WO2012174178.
AB  - The patent WO2012174178 claims the effect of a fully human antibody or antigen
      binding fragment of a human antibody which specifically binds and neutralizes,
      inhibits, blocks, abrogates, reduces or interferes with the activity of human
      angiopoietin-like protein 3 (hANGPTL3). The effects of human anti-hANGPTL3 mainly
      inhibit lipoprotein lipase activity and decrease triglyceride levels. In
      addition, it reduces plasma TC and high-density lipoprotein cholesterol in normal
      mice and mice with hyperlipoidemia and mimics the plasma profile of human
      familial combined hypolipidemia. The antibodies are useful in treating diseases
      or disorders associated with ANGPTL3, such as hyperlipidemia,
      hyperlipoproteinemia and other dyslipidemias. Furthermore, the anti-hANGPTL3
      antibodies can be administered to a subject to prevent or treat abnormal lipid
      metabolism which causes or enhances the induction of cardiovascular diseases. 

PMID- 24094084
TI  - A 2.8 A Fe-Fe separation in the Fe2(III/IV) intermediate, X, from Escherichia
      coli ribonucleotide reductase.
AB  - A class Ia ribonucleotide reductase (RNR) employs a MU-oxo-Fe2(III/III)/tyrosyl
      radical cofactor in its beta subunit to oxidize a cysteine residue ~35 A away in
      its alpha subunit; the resultant cysteine radical initiates substrate reduction.
      During self-assembly of the Escherichia coli RNR-beta cofactor, reaction of the
      protein's Fe2(II/II) complex with O2 results in accumulation of an Fe2(III/IV)
      cluster, termed X, which oxidizes the adjacent tyrosine (Y122) to the radical
      (Y122(*)) as the cluster is converted to the MU-oxo-Fe2(III/III) product. As the
      first high-valent non-heme-iron enzyme complex to be identified and the key
      activating intermediate of class Ia RNRs, X has been the focus of intensive
      efforts to determine its structure. Initial characterization by extended X-ray
      absorption fine structure (EXAFS) spectroscopy yielded a Fe-Fe separation (d(Fe
      Fe)) of 2.5 A, which was interpreted to imply the presence of three single-atom
      bridges (O(2-), HO(-), and/or MU-1,1-carboxylates). This short distance has been
      irreconcilable with computational and synthetic models, which all have d(Fe-Fe)
      >= 2.7 A. To resolve this conundrum, we revisited the EXAFS characterization of
      X. Assuming that samples containing increased concentrations of the intermediate
      would yield EXAFS data of improved quality, we applied our recently developed
      method of generating O2 in situ from chlorite using the enzyme chlorite dismutase
      to prepare X at ~2.0 mM, more than 2.5 times the concentration realized in the
      previous EXAFS study. The measured d(Fe-Fe) = 2.78 A is fully consistent with
      computational models containing a (MU-oxo)2-Fe2(III/IV) core. Correction of the
      d(Fe-Fe) brings the experimental data and computational models into full
      conformity and informs analysis of the mechanism by which X generates Y122(*).

PMID- 24094086
TI  - ACA standoff.

PMID- 24094085
TI  - The impact of Thai family matters on parent-adolescent sexual risk communication
      attitudes and behaviors.
AB  - This article reports on a combined family-based substance abuse and HIV
      prevention intervention targeting families with 13-14-year-old children in
      Bangkok, Thailand. Families (n = 340) were randomly and proportionally selected
      from 7 districts in Bangkok with half randomly assigned to an experimental or
      control condition. Families in the intervention condition were exposed to 5
      interactive booklets about adolescent substance use and risky sexual behavior.
      Trained health educators followed up by phone to encourage completion of each
      booklet. Primary outcomes reported in this article include whether the
      intervention increased the frequency of parent-child communication in general or
      about sexual risk taking in particular as well as whether the intervention
      reduced discomfort discussing sexual issues. The authors also tested to see
      whether booklet completion was associated with communication outcomes at the 6
      month follow-up. Multivariate findings indicate that the intervention had a
      significant impact on the frequency of general parent-child communication on the
      basis of child reports. The intervention had a marginal impact on the frequency
      of parent-child communication about sexual issues on the basis of parent reports.
      Booklet completion was associated with reduced discomfort discussing sex and was
      marginally associated with frequency of parent-child discussion of sex on the
      basis of parent reports only. These findings indicate that a family-based program
      can influence communication patterns. 

PMID- 24094087
TI  - Modulation of the insulin anabolic signalling cascade in growing chickens by n-3
      PUFA.
AB  - n-3 PUFA are crucial for health and development. Their effects as regulators of
      lipid and glucose metabolism are well documented. They also appear to affect
      protein metabolism, especially by acting on insulin sensitivity. The aim of the
      present study was to investigate the role of n-3 PUFA, i.e. the precursor alpha
      linolenic acid (ALA) 18:3n-3 or long-chain PUFA (LC-PUFA), in chickens, by
      focusing on their potential function as co-regulators of the insulin anabolic
      signalling cascade. Ross male broilers were divided into six dietary treatment
      groups. Diets were isoproteic (22 % crude protein) and isoenergetic (12.54 MJ
      metabolisable energy/kg) and contained similar lipid levels (6 %) provided by
      different proportions of various lipid sources: oleic sunflower oil rich in 18:1n
      9 as control; fish oil rich in LC-PUFA; rapeseed and linseed oils providing ALA.
      The provision of diets enriched with n-3 PUFA, i.e. rich in LC-PUFA or in the
      precursor ALA, for 3 weeks improved the growth performance of chickens, whereas
      that of only the ALA diet enhanced the development of the pectoralis major
      muscle. At 23 d of age, we studied the insulin sensitivity of the pectoralis
      major muscle and liver of chickens after an intravenous injection of insulin or
      saline. The present results indicate that the activation patterns of n-3 PUFA are
      different in the liver and muscles. An ALA-enriched diet may improve insulin
      sensitivity in muscles, with greater activation of the insulin-induced 70 kDa
      ribosomal protein S6 kinase/ribosomal protein S6 pathway involved in the
      translation of mRNA into proteins, thereby potentially increasing muscle protein
      synthesis and growth. Our findings provide a basis on which to optimise dietary
      fatty acid provision in growing animals.

PMID- 24094089
TI  - Balancing of ocean acidification by superoxide redox chemistry?

PMID- 24094090
TI  - A symptomatic Fabry disease mouse model generated by inducing
      globotriaosylceramide synthesis.
AB  - Fabry disease is a lysosomal storage disorder in which neutral
      glycosphingolipids, predominantly Gb3 (globotriaosylceramide), accumulate due to
      deficient alpha-Gal A (alpha-galactosidase A) activity. The GLAko (alpha-Gal A
      knockout) mouse has been used as a model for Fabry disease, but it does not have
      any symptomatic abnormalities. In the present study, we generated a symptomatic
      mouse model (G3Stg/GLAko) by cross-breeding GLAko mice with transgenic mice
      expressing human Gb3 synthase. G3Stg/GLAko mice had high Gb3 levels in major
      organs, and their serum Gb3 level at 5-25 weeks of age was 6-10-fold higher than
      that in GLAko mice of the same age. G3Stg/GLAko mice showed progressive renal
      impairment, with albuminuria at 3 weeks of age, decreased urine osmolality at 5
      weeks, polyuria at 10 weeks and increased blood urea nitrogen at 15 weeks. The
      urine volume and urinary albumin concentration were significantly reduced in the
      G3Stg/GLAko mice when human recombinant alpha-Gal A was administered
      intravenously. These data suggest that Gb3 accumulation is a primary pathogenic
      factor in the symptomatic phenotype of G3Stg/GLAko mice, and that this mouse line
      is suitable for studying the pathogenesis of Fabry disease and for preclinical
      studies of candidate therapies.

PMID- 24094093
TI  - Emerging tyrosine kinase inhibitors for head and neck cancer.
AB  - INTRODUCTION: Conventional treatments for head and neck squamous cell cancer
      (HNSCC) are not completely effective and present several issues in terms of
      toxicity. Treatments available consist of surgery, chemoradiotherapy and
      biological agents. AREAS COVERED: Tyrosine-kinase inhibitors (TKIs) alone or in
      combination, already tested or currently under investigation, will be evaluated
      together with their time placement along the treatment as well as the disease
      setting where they were used. EXPERT OPINION: From the results of the main trials
      on TKIs, it emerges that these agents added to chemotherapy in
      recurrent/metastatic setting do not represent the best approach because of the
      major side effects, worsened by the complex characteristics of treated patients,
      and the lack of gain in terms of efficacy. Targeted agents could better exploit
      their activity in other settings, such as either before local regional treatment
      or immediately after to modulate biological effects induced by the treatment
      itself (surgery and/or radiation) and/or concurrently with radiation. Future
      research should also focus on irreversible pan-HER inhibitors, or combination
      agents able to overcome primary and acquired resistance, and on relevant
      biomarkers that would allow for a better therapeutic index of these molecules.

PMID- 24094094
TI  - Cardiolipin and mitochondrial function in health and disease.
AB  - Cardiolipin (CL) is a unique phospholipid that is almost exclusively localized at
      the level of the inner mitochondrial membrane (IMM), where it is biosynthesized.
      This phospholipid is associated with membranes which are designed to generate an
      electrochemical gradient that is used to produce ATP. Such membranes include the
      bacterial plasma membrane and IMM. This ubiquitous and intimate association
      between CL and energy-transducing membranes suggests an important role for CL in
      mitochondrial bioenergetic processes. CL has been shown to interact with a number
      of IMM proteins, including the respiratory chain complexes and substrate
      carriers. Moreover, CL is involved in different stages of the mitochondrial
      apoptosis process as well as in mitochondrial membrane stability and dynamics.
      Alterations in CL structure, content, and acyl chain composition have been
      associated with mitochondrial dysfunction in multiple tissues in several
      physiopathological conditions and aging. In this review, we provide an overview
      of the roles of CL in mitochondrial function and bioenergetics in health and
      disease.

PMID- 24094095
TI  - The therapeutic potential of GPR120: a patent review.
AB  - INTRODUCTION: Type 2 diabetes (T2D) is a complex metabolic disorder characterized
      by persistent hyperglycemia and a wide range of underlying metabolic defects. The
      prevalence and incidence of T2D are expected to dramatically increase in the near
      future and consequently, there is a significant medical need for diabetes care.
      Many targets are under investigation to lower the plasma glucose levels or
      increase the insulin sensitivity. Despite newer drug classes emerging as viable
      long-term treatment options for the management of T2D, achieving an optimal
      glycemic control along with sufficient effectiveness over the course of the
      disease remains a challenge. In this regard, among several G-protein-coupled
      receptors (GPCRs), GPR120 and GPR40 have recently been considered as viable
      targets for diabetes and metabolic disorders. AREAS COVERED: This article reviews
      the current literature on the discovery and development of GPR120 agonists in
      diabetes and metabolic disorders and updates on the published patents in this
      field. The patent study for this review has been carried out using multiple
      electronic databases including SciFinder and Thomson Reuters Integrity. EXPERT
      OPINION: A paradigm shift in the treatment of diabetes is needed, wherein a
      single therapeutic agent could target diabetes and its associated disorders such
      as high plasma glucose level and inflammation, with excellent safety and
      tolerability profile. In this regard, agonists of GPR120 or dual-agonist GPR120
      and GPR40 are highly anticipated as therapeutic approaches for the treatment of
      diabetes on the basis of their novel glucose-dependent mechanism of action.

PMID- 24094096
TI  - Excitation BolsTORs motor neurons in ALS mice.
AB  - It is unclear why motor neurons selectively degenerate in amyotrophic lateral
      sclerosis (ALS). Saxena et al. (2013) demonstrate that excitation of motor
      neurons can prevent their demise in a mouse model of inherited ALS by a mechanism
      involving the mTOR pathway. 

PMID- 24094097
TI  - Acid indigestion in the endosome: linking signaling dysregulation to
      neurodevelopmental disorders.
AB  - The sodium-proton exchanger NHE6 contributes to proper endosomal acidification.
      NHE6 mutations are also linked to autism-related disorders. In this issue of
      Neuron, using NHE6-knockout mice, Ouyang et al. (2013) uncover how dysregulation
      of endosomal pH leads to disturbances in BDNF signaling and neuronal
      morphogenesis defects. 

PMID- 24094098
TI  - Exploiting exploration: past outcomes and future actions.
AB  - Applying past knowledge to future actions is crucial for adaptive choice
      behavior. Here, in this issue of Neuron, Donahue et al. (2013) show that reward
      enhances neural coding reliability for actions in a network of frontal and
      parietal brain areas. 

PMID- 24094099
TI  - The sacred disease: the puzzling genetics of epileptic disorders.
AB  - In the September 12, 2013 issue of Nature, the Epi4K Consortium (Allen et al.,
      2013) reported sequencing 264 patient trios with epileptic encephalopathies. The
      Consortium focused on genes exceptionally intolerant to sequence variations and
      found substantial interconnections with autism and intellectual disability gene
      networks. 

PMID- 24094100
TI  - Hox genes: choreographers in neural development, architects of circuit
      organization.
AB  - The neural circuits governing vital behaviors, such as respiration and
      locomotion, are comprised of discrete neuronal populations residing within the
      brainstem and spinal cord. Work over the past decade has provided a fairly
      comprehensive understanding of the developmental pathways that determine the
      identity of major neuronal classes within the neural tube. However, the steps
      through which neurons acquire the subtype diversities necessary for their
      incorporation into a particular circuit are still poorly defined. Studies on the
      specification of motor neurons indicate that the large family of Hox
      transcription factors has a key role in generating the subtypes required for
      selective muscle innervation. There is also emerging evidence that Hox genes
      function in multiple neuronal classes to shape synaptic specificity during
      development, suggesting a broader role in circuit assembly. This Review
      highlights the functions and mechanisms of Hox gene networks and their
      multifaceted roles during neuronal specification and connectivity. 

PMID- 24094101
TI  - The structure of cognition: attentional episodes in mind and brain.
AB  - Cognition is organized in a structured series of attentional episodes, allowing
      complex problems to be addressed through solution of simpler subproblems. A
      "multiple-demand" (MD) system of frontal and parietal cortex is active in many
      different kinds of tasks, and using data from neuroimaging, electrophysiology,
      neuropsychology, and cognitive studies of intelligence, I propose a core role for
      MD regions in assembly of the attentional episode. Monkey and human data show
      dynamic neural coding of attended information across multiple MD regions, with
      rapid communication within and between regions. Neuropsychological and imaging
      data link MD function to fluid intelligence, explaining some but not all
      "executive" deficits after frontal lobe lesions. Cognitive studies link fluid
      intelligence to goal neglect, and the problem of dividing complex task
      requirements into focused parts. Like the innate releasing mechanism of ethology,
      I suggest that construction of the attentional episode provides a core
      organizational principle for complex, adaptive cognition. 

PMID- 24094102
TI  - A theory of the transition to critical period plasticity: inhibition selectively
      suppresses spontaneous activity.
AB  - What causes critical periods (CPs) to open? For the best-studied case, ocular
      dominance plasticity in primary visual cortex in response to monocular
      deprivation (MD), the maturation of inhibition is necessary and sufficient. How
      does inhibition open the CP? We present a theory: the transition from pre-CP to
      CP plasticity arises because inhibition preferentially suppresses responses to
      spontaneous relative to visually driven input activity, switching learning cues
      from internal to external sources. This differs from previous proposals in (1)
      arguing that the CP can open without changes in plasticity mechanisms when
      activity patterns become more sensitive to sensory experience through circuit
      development, and (2) explaining not simply a transition from no plasticity to
      plasticity, but a change in outcome of MD-induced plasticity from pre-CP to CP.
      More broadly, hierarchical organization of sensory-motor pathways may develop
      through a cascade of CPs induced as circuit maturation progresses from "lower" to
      "higher" cortical areas. 

PMID- 24094103
TI  - Accelerated experience-dependent pruning of cortical synapses in ephrin-A2
      knockout mice.
AB  - Refinement of mammalian neural circuits involves substantial experience-dependent
      synapse elimination. Using in vivo two-photon imaging, we found that experience
      dependent elimination of postsynaptic dendritic spines in the cortex was
      accelerated in ephrin-A2 knockout (KO) mice, resulting in fewer adolescent spines
      integrated into adult circuits. Such increased spine removal in ephrin-A2 KOs
      depended on activation of glutamate receptors, as blockade of the N-methyl-D
      aspartate (NMDA) receptors eliminated the difference in spine loss between wild
      type and KO mice. We also showed that ephrin-A2 in the cortex colocalized with
      glial glutamate transporters, which were significantly downregulated in ephrin-A2
      KOs. Consistently, glial glutamate transport was reduced in ephrin-A2 KOs,
      resulting in an accumulation of synaptic glutamate. Finally, inhibition of glial
      glutamate uptake promoted spine elimination in wild-type mice, resembling the
      phenotype of ephrin-A2 KOs. Together, our results suggest that ephrin-A2
      regulates experience-dependent, NMDA receptor-mediated synaptic pruning through
      glial glutamate transport during maturation of the mouse cortex. 

PMID- 24094104
TI  - Experience-induced Arc/Arg3.1 primes CA1 pyramidal neurons for metabotropic
      glutamate receptor-dependent long-term synaptic depression.
AB  - A novel experience induces the Arc/Arg3.1 gene as well as plasticity of CA1
      neural networks. To understand how these are linked, we briefly exposed GFP
      reporter mice of Arc transcription to a novel environment. Excitatory synaptic
      function of CA1 neurons with recent in vivo Arc induction (ArcGFP+) was similar
      to neighboring noninduced neurons. However, in response to group 1 metabotropic
      glutamate receptor (mGluR) activation, ArcGFP+ neurons preferentially displayed
      long-term synaptic depression (mGluR-LTD) and robust increases in dendritic Arc
      protein. mGluR-LTD in ArcGFP+ neurons required rapid protein synthesis and Arc,
      suggesting that dendritic translation of Arc underlies the priming of mGluR-LTD.
      In support of this idea, novelty exposure increased Arc messenger RNA in CA1
      dendrites and promoted mGluR-induced translation of Arc in hippocampal
      synaptoneurosomes. Repeated experience suppressed synaptic transmission onto
      ArcGFP+ neurons and occluded mGluR-LTD ex vivo. mGluR-LTD priming in neurons with
      similar Arc activation history may contribute to encoding a novel environment. 

PMID- 24094105
TI  - Neuroprotection through excitability and mTOR required in ALS motoneurons to
      delay disease and extend survival.
AB  - Delaying clinical disease onset would greatly reduce neurodegenerative disease
      burden, but the mechanisms influencing early preclinical progression are poorly
      understood. Here, we show that in mouse models of familial motoneuron (MN)
      disease, SOD1 mutants specifically render vulnerable MNs dependent on endogenous
      neuroprotection signaling involving excitability and mammalian target of
      rapamycin (mTOR). The most vulnerable low-excitability FF MNs already exhibited
      evidence of pathology and endogenous neuroprotection recruitment early
      postnatally. Enhancing MN excitability promoted MN neuroprotection and reversed
      misfolded SOD1 (misfSOD1) accumulation and MN pathology, whereas reducing MN
      excitability augmented misfSOD1 accumulation and accelerated disease. Inhibiting
      metabotropic cholinergic signaling onto MNs reduced ER stress, but enhanced
      misfSOD1 accumulation and prevented mTOR activation in alpha-MNs. Modulating
      excitability and/or alpha-MN mTOR activity had comparable effects on the
      progression rates of motor dysfunction, denervation, and death. Therefore,
      excitability and mTOR are key endogenous neuroprotection mechanisms in
      motoneurons to counteract clinically important disease progression in ALS. 

PMID- 24094106
TI  - The specific alpha-neurexin interactor calsyntenin-3 promotes excitatory and
      inhibitory synapse development.
AB  - Perturbations of cell surface synapse-organizing proteins, particularly alpha
      neurexins, contribute to neurodevelopmental and psychiatric disorders. From an
      unbiased screen, we identify calsyntenin-3 (alcadein-beta) as a synapse
      organizing protein unique in binding and recruiting alpha-neurexins, but not beta
      neurexins. Calsyntenin-3 is present in many pyramidal neurons throughout cortex
      and hippocampus but is most highly expressed in interneurons. The transmembrane
      form of calsyntenin-3 can trigger excitatory and inhibitory presynapse
      differentiation in contacting axons. However, calsyntenin-3-shed ectodomain,
      which represents about half the calsyntenin-3 pool in brain, suppresses the
      ability of multiple alpha-neurexin partners including neuroligin 2 and LRRTM2 to
      induce presynapse differentiation. Clstn3-/- mice show reductions in excitatory
      and inhibitory synapse density by confocal and electron microscopy and
      corresponding deficits in synaptic transmission. These results identify
      calsyntenin-3 as an alpha-neurexin-specific binding partner required for normal
      functional GABAergic and glutamatergic synapse development.

PMID- 24094107
TI  - Cornichons control ER export of AMPA receptors to regulate synaptic excitability.
AB  - The strength of synaptic communication at central synapses depends on the number
      of ionotropic glutamate receptors, particularly the class gated by the agonist
      AMPA (AMPARs). Cornichon proteins, evolutionarily conserved endoplasmic reticulum
      cargo adaptors, modify the properties of vertebrate AMPARs when coexpressed in
      heterologous cells. However, the contribution of cornichons to behavior and in
      vivo nervous system function has yet to be determined. Here, we take a genetic
      approach to these questions by studying CNI-1--the sole cornichon homolog in C.
      elegans. cni-1 mutants hyperreverse, a phenotype associated with increased
      glutamatergic synaptic transmission. Consistent with this behavior, we find
      larger glutamate-gated currents in cni-1 mutants with a corresponding increase in
      AMPAR number. Furthermore, we observe opposite phenotypes in transgenic worms
      that overexpress CNI-1 or vertebrate homologs. In reconstitution studies, we
      provide support for an evolutionarily conserved role for cornichons in regulating
      the export of vertebrate and invertebrate AMPARs.

PMID- 24094108
TI  - Cytosolic transmitter concentration regulates vesicle cycling at hippocampal
      GABAergic terminals.
AB  - Sustained synaptic transmission requires vesicle recycling and refilling with
      transmitter, two processes considered to proceed independently. Contrary to this
      assumption, we show here that depletion of cytosolic transmitter at GABAergic
      synapses reversibly reduces the number of recycling vesicles. Using paired
      recordings in hippocampal cultures, we show that repetitive activity causes two
      phases of reduction of the postsynaptic response. The first involves the
      classical depletion of the readily releasable and recycling pools, while the
      second reflects impairment of vesicle filling as GABA is consumed, since it can
      only be reversed by uptake of GABA or its precursors, glutamate or glutamine.
      Surprisingly, this second phase is associated with reduced quantal release, a
      faster depression rate and lower FM5-95 labeling, suggesting that the size of the
      cycling vesicular pool is regulated by cytosolic transmitter availability.
      Regulation of vesicular cycling may represent a general mechanism of presynaptic
      plasticity, matching synaptic release to transmitter supply. 

PMID- 24094109
TI  - Repeated cocaine weakens GABA(B)-Girk signaling in layer 5/6 pyramidal neurons in
      the prelimbic cortex.
AB  - Repeated cocaine exposure triggers adaptations in layer 5/6 glutamatergic neurons
      in the medial prefrontal cortex (mPFC) that promote behavioral sensitization and
      drug-seeking behavior. While suppression of metabotropic inhibitory signaling has
      been implicated in these behaviors, underlying mechanisms are unknown. Here, we
      show that Girk/K(IR)3 channels mediate most of the GABA(B) receptor (GABA(B)R)
      dependent inhibition of layer 5/6 pyramidal neurons in the mPFC and that repeated
      cocaine suppresses this pathway. This adaptation was selective for GABA(B)R
      dependent Girk signaling in layer 5/6 pyramidal neurons of the prelimbic cortex
      (PrLC) and involved a D1/5 dopamine receptor- and phosphorylation-dependent
      internalization of GABA(B)R and Girk channels. Persistent suppression of Girk
      signaling in layer 5/6 of the dorsal mPFC enhanced cocaine-induced locomotor
      activity and occluded behavioral sensitization. Thus, the cocaine-induced
      suppression of GABA(B)R-Girk signaling in layer 5/6 pyramidal neurons of the
      prelimbic cortex appears to represent an early adaptation critical for promoting
      addiction-related behavior.

PMID- 24094110
TI  - Short neuropeptide F is a sleep-promoting inhibitory modulator.
AB  - To advance the understanding of sleep regulation, we screened for sleep-promoting
      cells and identified neurons expressing neuropeptide Y-like short neuropeptide F
      (sNPF). Sleep induction by sNPF meets all relevant criteria. Rebound sleep
      following sleep deprivation is reduced by activation of sNPF neurons, and flies
      experience negative sleep rebound upon cessation of sNPF neuronal stimulation,
      indicating that sNPF provides an important signal to the sleep homeostat. Only a
      subset of sNPF-expressing neurons, which includes the small ventrolateral clock
      neurons, is sleep promoting. Their release of sNPF increases sleep consolidation
      in part by suppressing the activity of wake-promoting large ventrolateral clock
      neurons, and suppression of neuronal firing may be the general response to sNPF
      receptor activation. sNPF acutely increases sleep without altering feeding
      behavior, which it affects only on a much longer time scale. The profound effect
      of sNPF on sleep indicates that it is an important sleep-promoting molecule. 

PMID- 24094111
TI  - A predictive network model of cerebral cortical connectivity based on a distance
      rule.
AB  - Recent advances in neuroscience have engendered interest in large-scale brain
      networks. Using a consistent database of cortico-cortical connectivity, generated
      from hemisphere-wide, retrograde tracing experiments in the macaque, we analyzed
      interareal weights and distances to reveal an important organizational principle
      of brain connectivity. Using appropriate graph theoretical measures, we show that
      although very dense (66%), the interareal network has strong structural
      specificity. Connection weights exhibit a heavy-tailed lognormal distribution
      spanning five orders of magnitude and conform to a distance rule reflecting
      exponential decay with interareal separation. A single-parameter random graph
      model based on this rule predicts numerous features of the cortical network: (1)
      the existence of a network core and the distribution of cliques, (2) global and
      local binary properties, (3) global and local weight-based communication
      efficiencies modeled as network conductance, and (4) overall wire-length
      minimization. These findings underscore the importance of distance and weight
      based heterogeneity in cortical architecture and processing. 

PMID- 24094112
TI  - Plasticity of recurrent l2/3 inhibition and gamma oscillations by whisker
      experience.
AB  - Local recurrent networks in neocortex are critical nodes for sensory processing,
      but their regulation by experience is much less understood than for long-distance
      (translaminar or cross-columnar) projections. We studied local L2/3 recurrent
      networks in rat somatosensory cortex during deprivation-induced whisker map
      plasticity, by expressing channelrhodopsin-2 (ChR2) in L2/3 pyramidal cells and
      measuring light-evoked synaptic currents in ex vivo S1 slices. In columns with
      intact whiskers, brief light impulses evoked recurrent excitation and supralinear
      inhibition. Deprived columns showed modestly reduced excitation and profoundly
      reduced inhibition, providing a circuit locus for disinhibition of whisker-evoked
      responses observed in L2/3 in vivo. Slower light ramps elicited sustained gamma
      frequency oscillations, which were nearly abolished in deprived columns.
      Reduction in gamma power was also observed in spontaneous LFP oscillations in
      L2/3 of deprived columns in vivo. Thus, L2/3 recurrent networks are a powerful
      site for homeostatic modulation of excitation-inhibition balance and regulation
      of gamma oscillations. 

PMID- 24094113
TI  - MiR-34a is up-regulated in response to low dose, low energy X-ray induced DNA
      damage in breast cells.
AB  - BACKGROUND: MicroRNAs are non-coding RNAs involved in the regulation of gene
      expression including DNA damage responses. Low doses of low energy X-ray
      radiation, similar to those used in mammographic exams, has been described to be
      genotoxic. In the present work we investigated the expression of miR-34a; a well
      described p53-regulated miRNA implicated in cell responses to X-ray irradiation
      at low doses. METHODS: Non-cancerous breast cell line MCF-10A and cancerous T-47D
      and MCF-7 cell lines were submitted to a low-energy X-ray irradiation (ranging
      from 28-30 Kv) using a dose of 5 Gy. The expression level of miR-34a, let-7a and
      miR-21 was assessed by qRT-PCR at 4 and 24 hours post-irradiation. DNA damage was
      then measured by comet assay and micronuclei estimation in MCF-10A and MCF-7 cell
      lines, where an increase of miR-34a levels could be observed after irradiation.
      The rate of apoptotic cells was estimated by nuclear staining and fluorescence
      microscopy. These experiments were also performed at low doses (3; 12 and 48 mGy)
      in MCF-10A and MCF-7 cell lines. RESULTS: We have observed an increase in miR-34a
      expression 4 hours post-irradiation at 5 Gy in MCF-10A and MCF-7 cell lines while
      its level did not change in T-47D, a breast cancer cell line bearing non
      functional p53. At low doses, miR-34a was up-regulated in non-tumoral MCF-10A to
      a higher extent as compared to MCF-7. MiR-34a levels decreased 24 hours post
      irradiation. We have also observed DNA damage and apoptosis at low-energy X-ray
      irradiation at low doses and the high dose in MCF-10A and MCF-7 4 and 24 hours
      post-irradiation relative to the mock control. CONCLUSION: Low energy X-ray is
      able to promote DNA strand breaks and miR-34a might be involved in cell responses
      to low energy X-ray DNA damage. MiR-34a expression correlates with X-ray dose,
      time after irradiation and cell type. The present study reinforces the need of
      investigating consequences of low dose X-ray irradiation of breast cells.

PMID- 24094115
TI  - Toward priorities for aging research.
AB  - The global population is aging, and although age remains the primary risk factor
      for all major causes of death, no priorities for aging research exist. After
      reviewing the literature on mortality modeling, we found that different chronic
      processes underlie mortality before and after reproductive age. To identify
      priorities in aging research, we propose a simple ranking method that uses the
      percentage of deaths attributable to each disease for the over 60 population on
      the basis that, rather than being the result of individual risk factors, these
      deaths are largely due to underlying senescent processes. Our ranking suggests
      that vascular aging, led by ischemic heart disease and stroke, is the most
      important focus for aging research. The availability of funding, however, is not
      currently aligned with health priorities, and we believe that rectifying this
      disconnect may improve societal health outcomes.

PMID- 24094114
TI  - "A draft Musa balbisiana genome sequence for molecular genetics in polyploid,
      inter- and intra-specific Musa hybrids".
AB  - BACKGROUND: Modern banana cultivars are primarily interspecific triploid hybrids
      of two species, Musa acuminata and Musa balbisiana, which respectively contribute
      the A- and B-genomes. The M. balbisiana genome has been associated with improved
      vigour and tolerance to biotic and abiotic stresses and is thus a target for Musa
      breeding programs. However, while a reference M. acuminata genome has recently
      been released (Nature 488:213-217, 2012), little sequence data is available for
      the corresponding B-genome.To address these problems we carried out Next
      Generation gDNA sequencing of the wild diploid M. balbisiana variety 'Pisang
      Klutuk Wulung' (PKW). Our strategy was to align PKW gDNA reads against the
      published A-genome and to extract the mapped consensus sequences for subsequent
      rounds of evaluation and gene annotation. RESULTS: The resulting B-genome is 79%
      the size of the A-genome, and contains 36,638 predicted functional gene sequences
      which is nearly identical to the 36,542 of the A-genome. There is substantial
      sequence divergence from the A-genome at a frequency of 1 homozygous SNP per 23.1
      bp, and a high degree of heterozygosity corresponding to one heterozygous SNP per
      55.9 bp. Using expressed small RNA data, a similar number of microRNA sequences
      were predicted in both A- and B-genomes, but additional novel miRNAs were
      detected, including some that are unique to each genome. The usefulness of this B
      genome sequence was evaluated by mapping RNA-seq data from a set of triploid AAA
      and AAB hybrids simultaneously to both genomes. Results for the plantains
      demonstrated the expected 2:1 distribution of reads across the A- and B-genomes,
      but for the AAA genomes, results show they contain regions of significant
      homology to the B-genome supporting proposals that there has been a history of
      interspecific recombination between homeologous A and B chromosomes in Musa
      hybrids. CONCLUSIONS: We have generated and annotated a draft reference Musa B
      genome and demonstrate that this can be used for molecular genetic mapping of
      gene transcripts and small RNA expression data from several allopolyploid banana
      cultivars. This draft therefore represents a valuable resource to support the
      study of metabolism in inter- and intraspecific triploid Musa hybrids and to help
      direct breeding programs.

PMID- 24094116
TI  - Albumin research in the 21st century.

PMID- 24094118
TI  - Schizotypy and personality profiles of Cluster A in a group of schizophrenic
      patients and their siblings.
AB  - BACKGROUND: Schizotypy, or the set of personality traits related to
      schizophrenia, is considered an endophenotypic manifestation that is more
      represented in first-degree relatives of patients with schizophrenia than in the
      general population. The assessment of schizotypy is primarily based on self
      reports, and for this reason it presents several limitations. In order to assess
      schizotypy, this study proposes a diagnostic instrument based on clinical
      reports. METHODS: A sample of 66 subjects, composed of 25 outpatients with
      schizophrenia, 18 siblings of these patients and 23 healthy controls, was
      subjected to the personality assessment test SWAP-200 by trained clinical
      interviewers. To test the hypothesis of the difference between the profiles of
      the Personality Disorders within the schizophrenia spectrum, a Multivariate
      Analysis of Variance and subsequent planned comparisons were conducted. RESULTS:
      Patients with schizophrenia scored higher than both their siblings and the
      controls on all SWAP-200 scales; their siblings, compared to the healthy
      controls, showed significant statistical differences, with higher mean scores for
      paranoid (F(1,63) = 7.02; p = 0.01), schizoid (F(1,63) = 6.56; p = 0.013) and
      schizotypal (F(1,63) = 6.47; p = 0.013) traits (PD T scores of Cluster A and Q
      factor scores for the schizoid scale [F(1,63) = 6.47; p = 0.013]). CONCLUSIONS:
      Consistent with previous data, first-degree relatives of patients with
      schizophrenia scored higher on schizophrenia-related personality traits than a
      general population comparison sample. SWAP-200, as an alternative diagnostic
      instrument to self-report measures, is able to reveal the higher prevalence of
      schizotypal traits in siblings of patients with schizophrenia, suggesting its
      possible use as a complementary instrument for the assessment of schizophrenia.

PMID- 24094119
TI  - Morphology control of nanofibril donor-acceptor heterojunction to achieve high
      photoconductivity: exploration of new molecular design rule.
AB  - Donor-acceptor nanofibril composites have been fabricated, and the dependence of
      their photocurrent response on the structure and morphology of the donor part has
      been systematically investigated. The nanofibril composites were composed of
      template nanofibers, assembled from an electron acceptor molecule, perylene
      tetracarboxylic diimide (PTCDI), onto which (through drop-casting) various
      electron donor molecules (D1-D4) were coated. The donor molecules have the same
      pi-conjugated core, but different side groups. Due to the different side groups,
      the four donor molecules showed distinctly different propensity for
      intermolecular aggregation, with D1-D3 forming segregated phases, while D4
      prefers homogeneous molecular distribution within the film. It was found that the
      nanofibril composites with D4 exhibit the highest photocurrent, whereas those
      with aggregation-prone D1-D3 exhibited much lower photocurrent under the same
      illumination condition. Solvent annealing is found to further enhance the
      aggregation of D1-D3 but facilitate more uniform molecular distribution of D4
      molecules. As a result, the photocurrent response of PTCDI fibers coated with D1
      D3 decreased after vapor annealing, whereas those coated with D4 further
      increased. The detrimental effect of the aggregation of donor molecules on the
      PTCDI fiber is likely due to the enhanced local electrical field built up by the
      high charge density around the aggregate-nanofiber interface, which hinders the
      charge separation of the photogenerated electron-hole pair. The results reported
      in this study give further insight into the molecular structural effect on
      photoconductivity of hybrid materials, particularly those based on donor-acceptor
      composites or interfaces, and provide new molecular design rules and material
      processing guidelines to achieve high photoconductivity. 

PMID- 24094121
TI  - Podcasts: personalizing publication.

PMID- 24094120
TI  - Lower extremity functional electrical stimulation cycling promotes physical and
      functional recovery in chronic spinal cord injury.
AB  - OBJECTIVE: To examine the effect of long-term lower extremity functional
      electrical stimulation (FES) cycling on the physical integrity and functional
      recovery in people with chronic spinal cord injury (SCI). DESIGN: Retrospective
      cohort, mean follow-up 29.1 months, and cross-sectional evaluation. SETTING:
      Washington University Spinal Cord Injury Neurorehabilitation Center, referral
      center. PARTICIPANTS: Twenty-five people with chronic SCI who received FES during
      cycling were matched by age, gender, injury level, and severity, and duration of
      injury to 20 people with SCI who received range of motion and stretching.
      INTERVENTION: Lower extremity FES during cycling as part of an activity-based
      restorative treatment regimen. MAIN OUTCOME MEASURE: Change in neurological
      function: motor, sensory, and combined motor-sensory scores (CMSS) assessed by
      the American Spinal Injury Association Impairment scale. Response was defined as
      >= 1 point improvement. RESULTS: FES was associated with an 80% CMSS responder
      rate compared to 40% in controls. An average 9.6 CMSS point loss among controls
      was offset by an average 20-point gain among FES subjects. Quadriceps muscle mass
      was on average 36% higher and intra/inter-muscular fat 44% lower, in the FES
      group. Hamstring and quadriceps muscle strength was 30 and 35% greater,
      respectively, in the FES group. Quality of life and daily function measures were
      significantly higher in FES group. CONCLUSION: FES during cycling in chronic SCI
      may provide substantial physical integrity benefits, including enhanced
      neurological and functional performance, increased muscle size and force
      generation potential, reduced spasticity, and improved quality of life.

PMID- 24094122
TI  - Promoting mother-infant interaction and infant mental health in low-income Korean
      families: attachment-based cognitive behavioral approach.
AB  - PURPOSE: This study evaluated the attachment-based cognitive behavioral approach
      (ACBA) to enhance mother-infant interaction and infant mental health. DESIGN AND
      METHODS: This quasi-experimental study used a pre-posttest control group design.
      Participants were 40 low-income, mother-infant (infant ages 12-36 months) dyads,
      20 dyads per group. The ACBA group received 10 weekly 90-min sessions. Dependent
      variables were changes in mother-infant interaction and infant mental health.
      Additionally, we explored changes in mothers' attachment security. RESULTS: The
      groups differed significantly in changes in mother-infant interaction, infant
      mental health problems, and mothers' attachment security. PRACTICE IMPLICATIONS:
      ACBA may enhance mother-infant interaction and infants' mental health.

PMID- 24094124
TI  - Perceptions of parents and children regarding asthma management responsibilities.
AB  - PURPOSE: The purpose of this study was to examine perceptions of children and
      parents regarding shared responsibilities for asthma management. DESIGN AND
      METHODS: The study included 72 children with asthma who were between the ages of
      7 and 12 years and their parents. Asthma management responsibilities were
      assessed by the "Asthma Responsibility Questionnaire." RESULTS: Disagreements
      occurred between parents and children on assuming responsibility. Children
      reported higher asthma management responsibility scores than reported by parents
      for them. PRACTICE IMPLICATIONS: It is important that nurses provide education
      and counseling to both children and their families to ensure that children take
      responsibility for disease management.

PMID- 24094123
TI  - Predictors of adolescents' health-promoting behaviors guided by primary
      socialization theory.
AB  - PURPOSE: The purpose of this study was to determine the influence of parents and
      peers on adolescents' health-promoting behaviors, framed by primary socialization
      theory. DESIGN AND METHOD: Longitudinal data collected annually from 1,081 rural
      youth (mean age = 17 +/- 0.7; 43.5% males; 44% Hispanic) and once from their
      parents were analyzed using generalized linear models. RESULTS: Parental
      monitoring and adolescent's religious commitment significantly predicted all
      health-promoting behaviors (nutrition, physical activity, safety, health
      practices awareness, and stress management). Other statistically significant
      predictors were parent's responsiveness and health-promoting behaviors. Peer
      influence predicted safety and stress management. PRACTICE IMPLICATIONS: Nurses
      may facilitate adolescents' development of health-promoting behaviors through
      family-focused interventions.

PMID- 24094125
TI  - Factors associated with the intention to recommend human papillomavirus
      vaccination among Korean school health teachers.
AB  - PURPOSE: The purposes were to examine Korean school health teachers' knowledge
      and attitudes toward human papillomavirus (HPV) and HPV vaccination, identify
      factors associated with their intention to recommend the HPV vaccine, and
      characterize school health teachers' communication with students or parents
      regarding the HPV vaccine. DESIGN AND METHODS: The online survey involved 119
      school health teachers in Korea. RESULTS: Factors associated with an intention to
      recommend the HPV vaccine were perceived benefits, desiring more education
      regarding HPV and the HPV vaccine, and age of school health teachers. PRACTICE
      IMPLICATIONS: Findings suggest a need for more education to promote a greater
      understanding of HPV and HPV vaccination among Korean school health teachers.

PMID- 24094126
TI  - Validation of a clinically useful measure of children's state anxiety before
      medical procedures.
AB  - PURPOSE: Assessment of children's anxiety in busy clinic settings is an important
      step in developing tailored interventions. This article describes the construct
      validation of the Children's Anxiety Meter-State (CAM-S), a brief measure of
      state anxiety. DESIGN AND METHODS: Existing data were used to investigate the
      associations between child self-reports of anxiety, parent reports of child
      anxiety, and observed child distress during an intravenous procedure. RESULTS:
      Children's (n = 421) CAM-S scores were significantly associated with all parent
      measures and observed distress ratings. PRACTICE IMPLICATIONS: Findings support
      the use of the CAM-S for assessment of child anxiety in clinical settings.

PMID- 24094127
TI  - Evaluation of child and parent outcomes after a pediatric cardiac camp
      experience.
AB  - PURPOSE: This study evaluated the effects of a cardiac camp experience on
      children with heart disease and their parents. DESIGN AND METHODS: A repeated
      measures design was used with 49 parent-child dyads. Repeated measures evaluated
      the effects of camp on anxiety, attitude toward illness, and psychosocial
      functioning of the children. Parental anxiety was also evaluated. RESULTS:
      Results demonstrated decreases in parent anxiety, decreases in child trait
      anxiety, and positive psychosocial outcomes in the areas of self-esteem, social,
      physical, and emotional functioning. PRACTICE IMPLICATIONS: Findings can be used
      to support decisions for those contemplating a camping experience for the child
      with heart disease.

PMID- 24094128
TI  - Under pressure: preventing pressure ulcers in critically ill infants.
AB  - PURPOSE: To determine whether a pressure ulcer prevention bundle was associated
      with a significant reduction in pressure ulcer development in infants in the
      pediatric intensive care unit. DESIGN AND METHODS: Quasi-experimental design
      involving 399 infants 0 to 3 months of age at a large tertiary care medical
      center. RESULTS: The implementation of the care bundle was associated with a
      significant drop in pressure ulcer incidence from 18.8 to 6.8%. PRACTICE
      IMPLICATIONS: Pressure ulcers can be prevented in the most vulnerable patients
      with the consistent implementation of evidence-based interventions and system
      supports to assist nurses with the change in practice.

PMID- 24094129
TI  - Perceptions of pediatric asthma in African American underserved families using
      metaphorical analysis.
AB  - PURPOSE: The purpose was to understand how African American children with asthma
      and their families living in underserved urban areas experience and perceive
      asthma. DESIGN AND METHODS: A narrative inquiry design with metaphorical analysis
      was used in this study with 20 African American children and their 10 families.
      RESULTS: Participants metaphorically viewed the family system as a functioning
      healthcare facility. Children didn't find their asthma abnormal but did use
      asthma symptoms to their advantage. Caregivers were viewed as first-line medical
      responders but often made errors in delivering medical treatment. Lack of
      knowledge relating to appropriate asthma interventions led to insufficient asthma
      care. PRACTICE IMPLICATIONS: Results provide evidence to improve patient-nurse
      interactions for this vulnerable patient group.

PMID- 24094130
TI  - Association between FAS and FASL genetic variants and risk of primary brain
      tumor.
AB  - The purpose of this study was to investigate whether functional polymorphisms of
      apoptosis pathway genes FAS and FASL are associated with the development of
      primary brain tumors. The study constituted 83 patients with primary brain tumor
      and 108 healthy individuals. In the present case-control study, the primary brain
      tumors were divided into two groups: gliomas and meningiomas. Evaluation of FAS 
      1377 G/A and FASL -844 T/C gene polymorphisms were performed by polymerase chain
      reaction (PCR) and restriction fragment length polymorphism (RFLP). To confirm
      the genotyping, results were examined by DNA sequencing method. Our results were
      analyzed by SPSS. The frequency of the FAS -1377 AA genotype was significantly
      lower in meningioma and glioma patients compared to controls (p = 0.023; p =
      0.001, respectively). Multivariate logistic regression analysis revealed that FAS
      -1377 AA genotype was associated with decreased risk of meningioma and glioma (OR
      = 0.092, 95% CI: 0.012-0.719, p = 0.023 for meningiomas; OR = 0.056, 95% CI:
      0.007-0.428, p = 0.006 for gliomas). However, there was no significant
      differences in FASL -844 T/C genotype frequencies between patients with primary
      brain tumors and controls (p > 0.05). In this study, combined genotypes were
      evaluated for association with primary brain tumors. Combined genotype analysis
      showed that the frequencies of AATC and AACC were significantly lower in glioma
      patients in comparison with those of controls (p = 0.023; p = 0.022,
      respectively). This study provides the first evidence that FAS -1377 AA genotype
      may have a protective effect on the developing primary brain tumor in a Turkish
      population. 

PMID- 24094131
TI  - Author's response to Maheshwari et al.

PMID- 24094132
TI  - Electron microscopy observation of TiO2 nanocrystal evolution in high-temperature
      atomic layer deposition.
AB  - Understanding the evolution of amorphous and crystalline phases during atomic
      layer deposition (ALD) is essential for creating high quality dielectrics,
      multifunctional films/coatings, and predictable surface functionalization.
      Through comprehensive atomistic electron microscopy study of ALD TiO2
      nanostructures at designed growth cycles, we revealed the transformation process
      and sequence of atom arrangement during TiO2 ALD growth. Evolution of TiO2
      nanostructures in ALD was found following a path from amorphous layers to
      amorphous particles to metastable crystallites and ultimately to stable
      crystalline forms. Such a phase evolution is a manifestation of the Ostwald
      Lussac Law, which governs the advent sequence and amount ratio of different
      phases in high-temperature TiO2 ALD nanostructures. The amorphous-crystalline
      mixture also enables a unique anisotropic crystal growth behavior at high
      temperature forming TiO2 nanorods via the principle of vapor-phase oriented
      attachment. 

PMID- 24094133
TI  - Trust in prescription drug brand websites: website trust cues, attitude toward
      the website, and behavioral intentions.
AB  - Direct-to-consumer (DTC) prescription drug brand websites, as a form of DTC
      advertising, are receiving increasing attention due to the growing number and
      importance as an ad and a consumer information source. This study examined
      consumer trust in a DTC website as an important factor influencing consumers'
      attitude toward the website and behavioral intention. Applying the conceptual
      framework of website trust, the particular focus of investigation was the effect
      of the website trust cue factor on consumers' perceived DTC website trust and
      subsequent attitudinal and behavioral responses. Results show a significant
      relation between the website trust cue factor and consumers' perceived DTC
      website trust. Perceived DTC website trust, in turn, was found to be
      significantly associated with consumers' attitude toward the DTC website and
      behavioral intention. 

PMID- 24094134
TI  - Evaluating the risk of patient re-identification from adverse drug event reports.
AB  - BACKGROUND: Our objective was to develop a model for measuring re-identification
      risk that more closely mimics the behaviour of an adversary by accounting for
      repeated attempts at matching and verification of matches, and apply it to
      evaluate the risk of re-identification for Canada's post-marketing adverse drug
      event database (ADE).Re-identification is only demonstrably plausible for deaths
      in ADE. A matching experiment between ADE records and virtual obituaries
      constructed from Statistics Canada vital statistics was simulated. A new re
      identification risk is considered, it assumes that after gathering all the
      potential matches for a patient record (all records in the obituaries that are
      potential matches for an ADE record), an adversary tries to verify these
      potential matches. Two adversary scenarios were considered: (a) a mildly
      motivated adversary who will stop after one verification attempt, and (b) a
      highly motivated adversary who will attempt to verify all the potential matches
      and is only limited by practical or financial considerations. METHODS: The mean
      percentage of records in ADE that had a high probability of being re-identified
      was computed. RESULTS: Under scenario (a), the risk of re-identification from
      disclosing the province, age at death, gender, and exact date of the report is
      quite high, but the removal of province brings down the risk significantly. By
      only generalizing the date of reporting to month and year and including all other
      variables, the risk is always low. All ADE records have a high risk of re
      identification under scenario (b), but the plausibility of that scenario is
      limited because of the financial and practical deterrent even for highly
      motivated adversaries. CONCLUSIONS: It is possible to disclose Canada's adverse
      drug event database while ensuring that plausible re-identification risks are
      acceptably low. Our new re-identification risk model is suitable for such risk
      assessments.

PMID- 24094135
TI  - Herpes zoster surveillance using electronic databases in the Valencian Community
      (Spain).
AB  - BACKGROUND: Epidemiologic data of Herpes Zoster (HZ) disease in Spain are scarce.
      The objective of this study was to assess the epidemiology of HZ in the Valencian
      Community (Spain), using outpatient and hospital electronic health databases.
      METHODS: Data from 2007 to 2010 was collected from computerized health databases
      of a population of around 5 million inhabitants. Diagnoses were recorded by
      physicians using the International Classification of Diseases, 9th Revision,
      Clinical Modification (ICD-9-CM). A sample of medical records under different
      criteria was reviewed by a general practitioner, to assess the reliability of
      codification. RESULTS: The average annual incidence of HZ was 4.60 per 1000
      persons-year (PY) for all ages (95% CI: 4.57-4.63), is more frequent in women
      [5.32/1000PY (95% CI: 5.28-5.37)] and is strongly age-related, with a peak
      incidence at 70-79 years. A total of 7.16/1000 cases of HZ required
      hospitalization. CONCLUSIONS: Electronic health database used in the Valencian
      Community is a reliable electronic surveillance tool for HZ disease and will be
      useful to define trends in disease burden before and after HZ vaccine
      introduction.

PMID- 24094136
TI  - HPV E6 oncoprotein as a potential therapeutic target in HPV related cancers.
AB  - INTRODUCTION: Human Papillomaviruses (HPVs) are the main etiological agents for
      the development of most ano-genital cancers and for a subset of head and neck
      neoplasias. The oncogenic capacity of HPV is due to the combined activity of the
      viral oncoproteins E6 and E7. A defining feature of all HPV associated cancers is
      the continued retention and expression of these two viral oncoproteins throughout
      the development of the disease, and this highlights their value as potential
      targets for therapeutic intervention, in HPV-induced malignancies. AREAS COVERED:
      In this review, the authors focus on the HPV E6 oncoprotein functions and its
      interactions with cellular targets containing either LxxLL motifs or PDZ domains.
      New approaches leading to the prevention such interactions are described, showing
      the advantage of E6 as a target for therapeutic intervention against malignant
      transformation and cancer. EXPERT OPINION: The high degree of conservation in E6
      LxxLL interactions across multiple HPV types makes this a compelling therapeutic
      target for pathologies caused by diverse HPV types. Combining this with
      therapeutics directed against E6-PDZ interactions offers great promise for the
      treatment of malignancies caused by high-risk HPV types.

PMID- 24094137
TI  - A safe anastomotic technique of using the transorally inserted anvil (OrVil) in
      Roux-en-Y reconstruction after laparoscopy-assisted total gastrectomy for
      proximal malignant tumors of the stomach.
AB  - BACKGROUND: To explore the safety and feasibility of the transorally inserted
      anvil (OrVil) in laparoscopy-assisted total gastrectomy for gastric cancer.
      METHODS: From December 2010 to June 2011, a total of 28 patients underwent
      laparoscopy-assisted total gastrectomy with a Roux-en-Y-esophagojejunostomy
      anastomosis with OrVil. Perioperative treatments, intraoperative data,
      postoperative complications and hospital length of stay were evaluated. RESULTS:
      There were no conversions to the open gastrectomy. The mean operation time was
      143 minutes and the mean blood loss was 70 ml. Patients resumed an oral liquid
      diet on postoperative days 4 to 5. Two patients (7%) who suffered postoperative
      aspiration pneumonia were cured by conservative treatment. The median hospital
      length of stay was 9.6 days (8 to 11 days), with no inhospital mortalities. The
      median follow-up time was 14.8 months (12 to 18 months), and postoperative
      endoscopic examination revealed no anastomosis stenosis in patients who had
      dysphagia. CONCLUSION: The use of the OrVil is technically feasible and
      relatively safe for Roux-en-Y reconstruction after laparoscopy-assisted total
      gastrectomy.

PMID- 24094140
TI  - Involvement of heparan sulfate in the renoprotective effects of imidapril, an
      angiotensin-converting enzyme inhibitor, in diabetic db/db mice.
AB  - We investigated the renoprotective effects of imidapril hydrochloride ((-)-(4 S)
      3-[(2 S)-2-[[(1 S)-1-ethoxycarbonyl-3-phenylpropyl] amino] propionyl]-1-methyl-2
      oxoimidazolidine-4-carboxylic acid hydrochloride, imidapril), an angiotensin
      converting enzyme inhibitor, in a diabetic animal model. We used BKS.Cg
      +Lepr(db)/+Lepr(db) (db/db) mice, a genetic animal model of obese type 2
      diabetes. Diabetic db/db mice suffered from glomerular hyperfiltration,
      albuminuria and hypoalbuminemia. Oral administration of 5 mg/kg/day of imidapril
      for 3 weeks suppressed renal hyperfiltration, reduced albuminuria and normalized
      hypoalbuminemia. Imidapril did not influence body weights, blood pressure or
      blood glucose concentrations in db/db mice. Urinary excretion of heparan sulfate
      (HS) in non-treated 11-week-old db/db mice was significantly lower than that in
      age-matched non-diabetic db/+m mice. HS is a component of HS proteoglycans, which
      are present in glomerular basement membranes and glycocalyx of cell surfaces.
      Reduced urinary HS excretion indicated glomerular HS loss in db/db mice.
      Imidapril increased urinary excretion of HS to concentrations observed in db/+m
      mice, indicating that imidapril prevented the loss of renal HS. These results
      suggest that imidapril ameliorates renal hyperfiltration and loss of renal
      contents of HS. Improvement of filtration function and maintenance of HS, which
      is an important structural component of glomeruli, may contribute to
      renoprotective effects of imidapril.

PMID- 24094141
TI  - The influence of beta-arrestin2 on cannabinoid CB1 receptor coupling to G
      proteins and subcellular localization and relative levels of beta-arrestin1 and 2
      in mouse brain.
AB  - CONTEXT: Beta-arrestins are known to couple to some G-protein-coupled receptors
      (GPCRs) to regulate receptor internalization, G-protein coupling and signal
      transduction, but have not been investigated for most receptors, and for very few
      receptors in vivo. Previous studies have shown that beta-arrestin2 deletion
      enhances the efficacy of specific cannabinoid agonists. OBJECTIVE: The present
      study hypothesized that brain cannabinoid CB1 receptors are regulated by beta
      arrestin2. METHODS: Beta-arrestin2+/+ and -/- mice were used. Western blotting
      was used to determine the relative levels of each beta-arrestin subtype in mouse
      brain. Receptor binding was measured to determine whether deletion of beta
      arrestin2 influences agonist binding to brain CB1 receptors, or the subcellular
      localization of CB1 in brain membranes subjected to differential centrifugation.
      A variety of cannabinoid agonists from different chemical classes were
      investigated for their ability to activate G-proteins in the presence and absence
      of beta-arrestin2 in cerebellum, hippocampus and cortex. RESULTS: No differences
      were found in the density of beta-arrestin1 or cannabinoid CB1 receptors in
      several brains of beta-arrestin2+/+ versus -/- mice. Differences between
      genotypes were found in the proportion of high- and low-affinity agonist binding
      sites in brain areas that naturally express higher levels of beta-arrestin2.
      Cortex from beta-arrestin2-/- mice contained less CB1 in the P1 fraction and more
      CB1 in the P2 fraction compared to beta-arrestin2+/+. Of the agonists assayed for
      activity, only Delta(9)-tetrahydrocannabinol (THC) exhibited a difference between
      genotypes, in that it was less efficacious in beta-arrestin2-/- than +/+ mouse
      membranes. CONCLUSION: Beta-arrestin2 regulates cannabinoid CB1 receptors in
      brain.

PMID- 24094142
TI  - Anorectal avulsion: an exceptional rectal trauma.
AB  - Anorectal avulsion is an exceptional rectal trauma in which the anus and
      sphincter no longer join the perineum and are pulled upward. As a result, they
      ventrally follow levator ani muscles. We present a rare case of a 29-years old
      patient who was admitted in a pelvic trauma context; presenting a complete
      complex anorectal avulsion. The treatment included a primary repair of the rectum
      and a diverting colostomy so as to prevent sepsis. Closure of the protective
      sigmoidostomy was performed seven months after the accident and the evolution was
      marked by an anal stenosis requiring iterative dilatations. 

PMID- 24094143
TI  - Trichinenlides A-T, mexicanolide-type limonoids from Trichilia sinensis.
AB  - Twenty new mexicanolide-type limonoids, namely, trichinenlides A-T (1-20), and 11
      known analogues were isolated from the leaves and twigs of Trichilia sinensis.
      Trichinenlides B (2) and C (3) and heytrijunolide D exhibited inhibition against
      lipopolysaccharide-induced nitric oxide production in RAW 264.7 macrophages with
      IC50 values of 2.85, 1.88, and 3.33 MUM, respectively. 

PMID- 24094145
TI  - Compliant eating of maternally prompted food predicts increased body mass index z
      score gain in girls: results from a population-based sample.
AB  - BACKGROUND: Poorer "division of responsibility" (DoR) feeding, characterized by
      high parental control and reduced child food choice, may promote pediatric
      obesity, although population-based prospective data are lacking. We tested
      whether poorer DoR feeding predicts childhood overweight/obesity onset and BMI z
      score gain, over 10 years in the National Longitudinal Study of Youth. METHODS:
      We studied 302 girls and 316 boys, with mean ages 52.24 and 52.35 months,
      respectively, in 1986, who were followed for 10 years. We excluded children who
      were initially overweight/obese. Mothers completed three DoR feeding questions in
      1986: (1) child eating compliance of prompted foods; (2) child eating compliance
      of initially refused foods; and (3) mother-allotted child food choice. Child BMI
      (kg/m(2)) was calculated from measured weights and heights in 1986, 1988, 1992,
      1994, and 1996. RESULTS: Daughters who complied with maternal food prompts [odds
      ratio (OR), 2.01] and those who obeyed maternal prompts to consume initially
      rejected foods (OR, 2.29) "most of the time" were significantly more likely than
      daughters who complied less frequently to become overweight/obese after 8 years.
      Also, more frequent eating compliance (p<0.001) and more frequent compliance of
      initially rejected foods (p=0.003) predicted greater BMI z-score gain in girls.
      These associations were not found for boys. Maternal obesity consistently
      predicted overweight/obesity risk in girls (ORs, 2.48-8.63) and boys (ORs, 2.27-
      4.03). CONCLUSIONS: Teaching parents to avoid coercive feeding practices, while
      encouraging child self-selection of healthier foods, may help their daughters to
      achieve better energy balance.

PMID- 24094146
TI  - The childhood obesity research demonstration project: a comprehensive community
      approach to reduce childhood obesity.

PMID- 24094144
TI  - Associations of serum insulin-like growth factor-I and insulin-like growth factor
      binding protein 3 levels with biomarker-calibrated protein, dairy product and
      milk intake in the Women's Health Initiative.
AB  - It is well established that protein-energy malnutrition decreases serum insulin
      like growth factor (IGF)-I levels, and supplementation of 30 g of whey protein
      daily has been shown to increase serum IGF-I levels by 8 % after 2 years in a
      clinical trial. Cohort studies provide the opportunity to assess associations
      between dietary protein intake and IGF axis protein levels under more typical
      eating conditions. In the present study, we assessed the associations of
      circulating IGF axis protein levels (ELISA, Diagnostic Systems Laboratories) with
      total biomarker-calibrated protein intake, as well as with dairy product and milk
      intake, among postmenopausal women enrolled in the Women's Health Initiative (n
      747). Analyses were carried out using multivariate linear regression models that
      adjusted for age, BMI, race/ethnicity, education, biomarker-calibrated energy
      intake, alcohol intake, smoking, physical activity and hormone therapy use. There
      was a positive association between milk intake and free IGF-I levels. A three
      serving increase in milk intake per d (approximately 30 g of protein) was
      associated with an estimated average 18.6 % higher increase in free IGF-I levels
      (95 % CI 0.9, 39.3 %). However, total IGF-I and insulin-like growth factor
      binding protein 3 (IGFBP-3) levels were not associated with milk consumption and
      nor were there associations between biomarker-calibrated protein intake,
      biomarker-calibrated energy intake, and free IGF-I, total IGF-I or IGFBP-3
      levels. The findings of the present study carried out in postmenopausal women are
      consistent with clinical trial data suggesting a specific relationship between
      milk consumption and serum IGF-I levels, although in the present study this
      association was only statistically significant for free, but not total, IGF-I or
      IGFBP-3 levels.

PMID- 24094147
TI  - In vivo type 2 cannabinoid receptor-targeted tumor optical imaging using a near
      infrared fluorescent probe.
AB  - The type 2 cannabinoid receptor (CB2R) plays a vital role in carcinogenesis and
      progression and is emerging as a therapeutic target for cancers. However, the
      exact role of CB2R in cancer progression and therapy remains unclear. This has
      driven the increasing efforts to study CB2R and cancers using molecular imaging
      tools. In addition, many types of cancers overexpress CB2R, and the expression
      levels of CB2R appear to be associated with tumor aggressiveness. Such
      upregulation of the receptor in cancer cells provides opportunities for CB2R
      targeted imaging with high contrast and for therapy with low side effects. In the
      present study, we report the first in vivo tumor-targeted optical imaging using a
      novel CB2R-targeted near-infrared probe. In vitro cell fluorescent imaging and a
      competitive binding assay indicated specific binding of NIR760-mbc94 to CB2R in
      CB2-mid delayed brain tumor (DBT) cells. NIR760-mbc94 also preferentially labeled
      CB2-mid DBT tumors in vivo, with a 3.7-fold tumor-to-normal contrast enhancement
      at 72 h postinjection, whereas the fluorescence signal from the tumors of the
      mice treated with NIR760 free dye was nearly at the background level at the same
      time point. SR144528, a CB2R competitor, significantly inhibited tumor uptake of
      NIR760-mbc94, indicating that NIR760-mbc94 binds to CB2R specifically. In
      summary, NIR760-mbc94 specifically binds to CB2R in vitro and in vivo and appears
      to be a promising molecular tool that may have great potential for use in
      diagnostic imaging of CB2R-positive cancers and therapeutic monitoring as well as
      in elucidating the role of CB2R in cancer progression and therapy. 

PMID- 24094148
TI  - Disulfide-containing high mobility group box-1 promotes N-methyl-D-aspartate
      receptor function and excitotoxicity by activating Toll-like receptor 4-dependent
      signaling in hippocampal neurons.
AB  - AIMS: Using primary cultures of mouse hippocampal neurons, we studied the
      molecular and functional interactions between high mobility group box-1 (HMGB1)
      and the N-methyl-d-aspartate receptor (NMDAR), two proteins playing a key role in
      neuronal hyperexcitability. By measuring NMDA-induced calcium (Ca(2+)) increase
      in neuronal somata and neurotoxicity as functional read-out parameters, we
      explored the role of the redox state of HMGB1, the receptor involved, and the
      molecular signaling underlying its interactions with postsynaptic NMDAR. We also
      investigated whether HMGB1 redox state affects its proconvulsive effects in mice.
      RESULTS: Nonoxidizable HMGB1 with a triple cysteine-to-serine replacement (3S
      HMGB1) was ineffective on NMDA response. Conversely, the disulfide-containing
      form of HMGB1 dose dependently enhanced NMDA-induced Ca(2+) increase in neuronal
      cell bodies. This effect was prevented by BoxA, a competitive HMGB1 antagonist,
      and by Rhodobacter sphaeroides lipopolysaccharide (LPS-RS), a toll-like receptor
      4 (TLR4) selective antagonist, and it was abrogated in neurons lacking TLR4 while
      persisting in the absence of receptor for advanced glycation end products (RAGE).
      TLR4 and NMDAR subunit 1 (NR1) and 2B (NR2B) were colocalized in neurons.
      Disulfide HMGB1 effect on NMDA-induced Ca(2+) influx was prevented by 3-O
      methylsphingomyelin (3-O-MS) and 4-amino-5-(4-chlorophenyl)-7-(t-butyl) pyrazolo
      [3,4-d] pyrimidine, (PP2) selective inhibitors of neutral sphingomyelinase and
      Src-family Tyr kinases, respectively. Disulfide HMGB1, but not 3S-HMGB1,
      increased Tyr(1472) phosphorylation of the NR2B subunit of the NMDAR, which is
      known to increase Ca(2+) channel permeability. Similarly, disulfide HMGB1
      increased NMDA-induced neuronal cell death in vitro and enhanced kainate-induced
      seizures in vivo. INNOVATION AND CONCLUSION: We describe a novel molecular
      neuronal pathway activated by HMGB1 that could be targeted in vivo to prevent
      neurodegeneration and seizures mediated by excessive NMDARs stimulation.

PMID- 24094149
TI  - Conformational analysis of chiral supramolecular aggregates: modeling the subtle
      difference between hydrogen and deuterium.
AB  - A detailed analysis of the conformational states of self-assembled,
      stereoselectively deuterated benzene-1,3,5-tricarboxamides ((S,S,S)-D-BTAs)
      reveals four different conformers for the supramolecular polymers. The relative
      amount of the conformers depends on the solvent structure and the temperature.
      With the help of a model, the thermodynamic parameters that characterize the
      different conformational states were quantified as well as the amount of the
      species that occur at different stages of the polymerization process. The results
      show that small changes in the stability between different types of conformers
      formed by (S,S,S)-D-BTAs-in the order of a few J mol(-1)-arise from the
      combination of interactions between the solvent/supramolecular aggregate,
      temperature, and solvent structure. While the introduction of a deuterium label
      allows to sensitively probe the solvophobic effects in the supramolecular
      aggregation, a rationalization of the observed effects on a molecular level is
      not yet straightforward but is proposed to result from subtle effects in the
      vibrational enthalpy and entropy terms of the isotope effect.

PMID- 24094150
TI  - Contrast agents for MRI.
AB  - Contrast agents are divided into two categories. The first one is paramagnetic
      compounds, including lanthanides like gadolinium, which mainly reduce the
      longitudinal (T1) relaxation property and result in a brighter signal. The second
      class consists of super-paramagnetic magnetic nanoparticles (SPMNPs) such as iron
      oxides, which have a strong effect on the transversal (T2) relaxation properties.
      SPMNPs have the potential to be utilized as excellent probes for magnetic
      resonance imaging (MRI). For instance, clinically benign iron oxide and
      engineered ferrite nanoparticles provide a good MRI probing capability for
      clinical applications. Furthermore, the limited magnetic property and inability
      to escape from the reticuloendothelial system (RES) of the used nanoparticles
      impede their further advancement. Therefore, it is necessary to develop the
      engineered magnetic nanoparticle probes for the next-generation molecular MRI.
      Considering the importance of MRI in diagnosing diseases, this paper presents an
      overview of recent scientific achievements in the development of new synthetic
      SPMNP probes whereby the sensitive and target-specific observation of biological
      events at the molecular and cellular levels is feasible. 

PMID- 24094151
TI  - Silanized polymeric nanoparticles for DNA isolation.
AB  - The aim of this study is to prepare silanized polymeric nanoparticles for DNA
      isolation. Polymeric p(HEMA)-IMEO-PBA nanoparticles around 85.7 nm diameter, was
      obtained by surfactant free emulsion polymerization for DNA isolation.
      Synthesized nanoparticles for characterization studies were realized scanning
      electron microscopy (SEM), Fourier transform infrared spectroscopy (FTIR), and
      Zeta-size. Surface area, average particle size and size distribution were also
      performed. The surface area of synthesized silanized polymeric nanoparticles was
      2460 m(2)/g. Synthesized polymeric nanoparticles were silanized with 3-(2
      imidazoline-1-yl)propyl (triethoxysilane) (IMEO). After that, phenylboronic acid
      (PBA) which is DNA specific ligand were covalently binded to silanized polymeric
      nanoparticles. The amount of DNA adsorbed onto the p(HEMA)-IMEO-PBA nanoparticles
      first increased and then reached a saturation value at around 14.0 mg/mL of DNA
      concentration. The maximum adsorption was 672.41 mg/g silanized polymeric
      nanoparticles in the optimum adsorption medium. The maximum DNA adsorption was
      achieved at 4 degrees C. The overall recovery of DNA was calculated as 95%. In
      repetitive adsorption-desorption circles, it is observed not being important
      decrease in DNA adsorption capacities. The results were shown that silanized
      polymeric nanoparticles can be a good alternative for DNA isolation.

PMID- 24094152
TI  - Modified insulator semiconductor electrode with functionalized nanoparticles for
      Proteus mirabilis bacteria biosensor development.
AB  - The development of enzymatic sensors for biological purposes such as biomedicine,
      pharmacy, food industry, and environmental toxicity requires the purification
      step of the enzyme. To prevent the loss of the enzyme activity, a new strategy is
      held in order to immobilize the bacteria. It will constitute the biological
      sensing element leading to a high operational stability and multiple adaptations
      to various conditions such as temperature, pH and ionic strength changes. In this
      work we describe the development of a urea biosensor by immobilizing Proteus
      mirabilis bacteria onto an insulator-semiconductor electrode on functionalized
      Fe3O4 nanoparticles (NPs), using cationic, Poly (allylamine hydrochloride) then
      anionic, Poly (sodium 4-styrenesulfonate) polyelectrolytes, BSA (serum bovin
      albumin), and glutaraldehyde as a cross-linking agent. The response of P.
      mirabilis to urea addition is evaluated in homogeneous and heterogeneous phases.
      Before the immobilization step, the activity of urease produced from the P.
      mirabilis bacteria was attempted using the ion ammonium selective electrodes
      (ISEs). Adhesion of the bacteria cells on IS electrodes have been studied using
      contact angle measurements. After immobilization of the bacteria, on the
      (Si/SiO2/Si3N4) and (Si/SiO2) substrates, the relationship between the evolution
      of the flat band potential ?VFB and the urea concentration is found to be linear
      for values ranging from 10(-2)M to 10(-5)M. 

PMID- 24094153
TI  - Effects of surface modification on the mechanical and structural properties of
      nanofibrous poly(epsilon-caprolactone)/forsterite scaffold for tissue engineering
      applications.
AB  - Composite scaffolds consisting of polymers reinforced with ceramic nanoparticles
      are widely applied for hard tissue engineering. However, due to the incompatible
      polarity of ceramic nanoparticles with polymers, they tend to agglomerate in the
      polymer matrix which results in undesirable effects on the integral properties of
      composites. In this research, forsterite (Mg2SiO4) nanoparticles was surface
      esterified by dodecyl alcohol and nanofibrous poly(epsilon
      caprolactone)(PCL)/modified forsterite scaffolds were developed through
      electrospinning technique. The aim of this research was to investigate the
      properties of surface modified forsterite nanopowder and PCL/modified forsterite
      scaffolds, before and after hydrolytic treatment, as well as the cellular
      attachment and proliferation. Results demonstrated that surface modification of
      nanoparticles significantly enhanced the tensile strength and toughness of
      scaffolds upon 1.5- and 4-folds compared to unmodified samples, respectively, due
      to improved compatibility between matrix and filler. Hydrolytic treatment of
      scaffolds also modified the bioactivity and cellular attachment and proliferation
      due to greatly enhanced hydrophilicity of the forsterite nanoparticles after this
      process compared to surface modified samples. Results suggested that surface
      modification of forsterite nanopowder and hydrolytic treatment of the developed
      scaffolds were effective approaches to address the issues in the formation of
      composite fibers and resulted in development of bioactive composite scaffolds
      with ideal mechanical and structural properties for bone tissue engineering
      applications. 

PMID- 24094154
TI  - Rapid screening of potential metallic glasses for biomedical applications.
AB  - This paper presents a rapid screening process to select potential titanium and
      zirconium based metallic glasses (MGs) for bio-material applications.
      Electrochemical activity of 7 MGs including 6 bulk metallic glasses and 1 thin
      film deposited MG in simulation body and human serum is first inspected. A low
      voltage potential state test is also developed to simulate the cell membrane
      potential that the implant MGs will suffer. Results show that the MGs composed of
      Ti65Si15Ta10Zr10 and Ta57Zr23Cu12Ti8 exhibit excellent electrochemical stability
      in both simulation body fluid and human serum. In addition, the copper content in
      the MGs plays an important role on the electrochemical activity. MGs with the
      copper content higher than 17.5% show significant electrochemical responses. The
      cytotoxicity of the solid MG samples and the corrosion released ions are also
      evaluated by an in-vitro MTT test utilizing the murine bone marrow stem cells.
      Results indicate that all the solid MG samples show no acute cytotoxicity yet the
      corrosion released ions show significant toxicity for murine bone marrow stem
      cells. The rapid screening process developed in the present study suggests that
      the Ti65Si15Ta10Zr10 metallic glass has high potential for biomedical
      applications due to its good electrochemical stability and very low cytotoxicity.

PMID- 24094155
TI  - Application of graphene-ionic liquid-chitosan composite-modified carbon molecular
      wire electrode for the sensitive determination of adenosine-5'-monophosphate.
AB  - In this paper, a graphene (GR) ionic liquid (IL) 1-octyl-3-methylimidazolium
      hexafluorophosphate and chitosan composite-modified carbon molecular wire
      electrode (CMWE) was fabricated by a drop-casting method and further applied to
      the sensitive electrochemical detection of adenosine-5'-monophosphate (AMP). CMWE
      was prepared with diphenylacetylene (DPA) as the modifier and the binder. The
      properties of modified electrode were examined by scanning electron microscopy,
      cyclic voltammetry and electrochemical impedance spectroscopy. Electrochemical
      behaviors of AMP was carefully investigated with enhanced responses appeared,
      which was due to the presence of GR-IL composite on the electrode surface with
      excellent electrocatalytic ability. A well-defined oxidation peak of AMP appeared
      at 1.314 V and the electrochemical parameters were calculated by electrochemical
      methods. Under the selected conditions, the oxidation peak current of AMP was
      proportional to its concentration in the range from 0.01 MUM to 80.0 MUM with the
      detection limit as 3.42 nM (3sigma) by differential pulse voltammetry. The
      proposed method exhibited good selectivity and was applied to the detection of
      vidarabine monophosphate injection samples with satisfactory results.

PMID- 24094156
TI  - Identification of diffusive transport properties of poly(vinyl alcohol) hydrogels
      from reservoir test.
AB  - In this paper the identification of diffusion coefficient, retardation factor and
      surface distribution coefficient for selected salts in poly(vinyl alcohol)
      hydrogels is performed. The identification of the transport parameters is based
      on the previously developed inverse problem technique using experimental data
      from the reservoir test and the solution of the diffusive transport equation with
      linear equilibrium sorption. The estimated values of diffusion coefficient are:
      for physiological fluid (6.30+/-0.10)*10(-10) m(2)/s, for 1 M NaCl (6.42+/
      0.39)*10(-10) m(2)/s, and for 1 M KCl (7.94+/-0.38)*10(-10) m(2)/s. The
      retardation factor for all tested materials and salts is equal or close to one.
      The average value of the effective surface distribution coefficient is equal to
      0.5.

PMID- 24094157
TI  - Preparation and characterization of nano-hydroxyapatite within chitosan matrix.
AB  - Nano-composites that show some features of natural bone both in composition and
      in microstructure have been prepared by in situ precipitation method. Apatite
      phase has been prepared from cost-effective precursors (calcite and urea
      phosphate) within chitosan (CS) matrix dissolved in aqueous acetic acid solution.
      The compositional and morphological properties of composites were studied by
      means of Fourier transform infrared (FTIR) spectroscopy, X-ray diffraction (XRD)
      thermogravimetric analysis (TGA) and transmission electron microscopy (TEM).
      Depending on the reaction conditions (temperature, reaction time, glucose
      addition and pH control) in addition to hydroxyapatite (HA) as a major phase,
      octacalcium hydrogen phosphate pentahydrate (OCP) and dicalcium phosphate
      anhydrate (DCPD) were formed as shown by XRD and FTIR. Crystallite lengths of
      precipitated HA estimated by Scherrer's equation were between 20 and 30 nm. A
      fibrous morphology (~400 nm) of HA observed by TEM indicates that HA nucleates on
      chitosan chains.

PMID- 24094158
TI  - Co-delivery of drug and DNA from cationic dual-responsive micelles derived from
      poly(DMAEMA-co-PPGMA).
AB  - The synthesis and gene transfection efficiency of a series of amphiphilic
      copolymers with poly(dimethylaminoethyl methacrylate) (PDMAEMA), and
      poly(propylene glycol methacrylate) (PPGMA) segments is reported. The hydrophobic
      PPGMA interior allows a cell-sensitizing drug such as paclitaxel to be
      incorporated while the cationic and hydrophilic PDMAEMA corona allows the
      complexation of anionic DNA to form a nano-sized polyplex. These drug
      encapsulated copolymers display excellent gene transfection efficiency as
      compared to PEI or PDMAEMA homopolymers. 

PMID- 24094159
TI  - Microstructure evolution and mechanical properties of a Ti-35Nb-3Zr-2Ta
      biomedical alloy processed by equal channel angular pressing (ECAP).
AB  - In this paper, an equal channel angular pressing method is employed to refine
      grains and enhance mechanical properties of a new beta Ti-35Nb-3Zr-2Ta biomedical
      alloy. After the 4th pass, the ultrafine equiaxed grains of approximately 300 nm
      and 600 nm are obtained at pressing temperatures of 500 and 600 degrees C
      respectively. The SEM images of billets pressed at 500 degrees C reveal the
      evolution of shear bands and finally at the 4th pass intersectant networks of
      shear bands, involving initial band propagation and new band broadening, are
      formed with the purpose of accommodating large plastic strain. Furthermore, a
      unique herringbone microstructure of twinned martensitic variants is observed in
      TEM images. The results of microhardness measurements and uniaxial tensile tests
      show a significant improvement in microhardness and tensile strength from 534 MPa
      to 765 MPa, while keeping a good level of ductility (~16%) and low elastic
      modulus (~59 GPa). The maximum superelastic strain of 1.4% and maximum recovered
      strain of 2.7% are obtained in the billets pressed at 500 degrees C via the 4th
      pass, which exhibits an excellent superelastic behavior. Meanwhile, the effects
      of different accumulative deformations and pressing temperatures on
      superelasticity of the ECAP-processed alloys are investigated.

PMID- 24094160
TI  - Rapid preparation of pH-sensitive polymeric nanoparticle with high loading
      capacity using electrospray for oral drug delivery.
AB  - Drug loading capacity is an important property for an ideal drug delivery system.
      However, the drug loading capacity of prepared pH-sensitive polymeric
      nanoparticles is usually low. To overcome this drawback, the electrospray method
      was used to prepare Eudragit L 100-55 nanoparticles with high drug loading
      capacity in one step. Omeprazole was selected as the model drug. The maximum
      loading capacity of nanoparticles was 43.21% by changing the mass ratio of drug
      to polymer, and the entrapment efficiency was nearly 100%. The prepared
      nanoparticle showed spherical or ellipsoidal morphology and the average diameter
      was about 300 nm. The pH-sensitive nanoparticle displayed pH-dependent release in
      vitro. In addition, a slight cytotoxicity was detected in the cytotoxicity study.
      The results indicated that electrospray is an easy, rapid and efficient technique
      for the preparation of high-loading pH-sensitive polymeric nanoparticles, and the
      pH-sensitive nanoparticle is a promising carrier for oral drug delivery.

PMID- 24094161
TI  - XRD and FTIR crystallinity indices in sound human tooth enamel and synthetic
      hydroxyapatite.
AB  - The crystallinity index (CI) is a measure of the percentage of crystalline
      material in a given sample and it is also correlated to the degree of order
      within the crystals. In the literature two ways are reported to measure the CI: X
      ray diffraction and infrared spectroscopy. Although the CI determined by these
      techniques has been adopted in the field of archeology as a structural order
      measure in the bone with the idea that it can help e.g. in the sequencing of the
      bones in chronological and/or stratigraphic order, some debate remains about the
      reliability of the CI values. To investigate similarities and differences between
      the two techniques, the CI of sound human tooth enamel and synthetic
      hydroxyapatite (HAP) was measured in this work by X-ray diffraction (XRD) and
      Fourier Transform Infrared spectroscopy (FTIR), at room temperature and after
      heat treatment. Although the (CI)XRD index is related to the crystal structure of
      the samples and the (CI)FTIR index is related to the vibration modes of the
      molecular bonds, both indices showed similar qualitative behavior for heat
      treated samples. At room temperature, the (CI)XRD value indicated that enamel is
      more crystalline than synthetic HAP, while (CI)FTIR indicated the opposite.
      Scanning (SEM) and transmission (TEM) images were also used to corroborate the
      measured CI values. 

PMID- 24094162
TI  - Antimycobacterial efficacy of silver nanoparticles as deposited on porous
      membrane filters.
AB  - Environmental mycobacteria pose a significant health burden. Non-tuberculous
      mycobacteria infections have been traced to water treatment networks, where
      mycobacterial biofilms are ubiquitous. Filters that remove potential pathogens
      have significant medical applications. The purpose of this study is to
      demonstrate that an antibacterial silver nanoparticle (AgNP) coating can prevent
      colonization and growth of a mycobacterial biofilm on a filter material. The
      antibacterial efficacy of commercially available AgNPs was measured against
      Mycobacterium avium, Mycobacterium smegmatis, and Mycobacterium marinum after 48
      h in liquid culture. Nanoparticles were deposited on micro-porous track etched
      polycarbonate membranes. The growth of biofilms on the membranes was observed by
      microscopy and counting colony forming units. M. smegmatis was most susceptible
      to AgNPs, with a 98.7% reduction at 100 MUM AgNP concentration. M. avium was
      reduced by 97.3% at 539 MUM AgNP after 48 h. Deposited nanoparticles inhibited
      colonization and growth for both M. smegmatis and M. avium on the membrane
      surface. Similar to the liquid culture, M. avium (84.2% survival) was more
      resistant than M. smegmatis (0.03% survival).

PMID- 24094163
TI  - The effects of loading conditions and specimen environment on the nanomechanical
      response of canine cortical bone.
AB  - Bone is a viscoelastic connective tissue composed primarily of mineral and type I
      collagen, which interacts with water, affecting its mechanical properties.
      Therefore, both the level of hydration and the loading rate are expected to
      influence the measured nanomechanical response of bone. In this study, we
      investigated the influence of three distinct hydration conditions, peak loads and
      loading/unloading rates on the elastic modulus and hardness of canine femoral
      cortical bone via nanoindentation. Sections from three canine femurs from
      multiple regions of the diaphysis were tested for a total of 670 indentations.
      All three hydration conditions (dry, moist and fully hydrated tissue) were tested
      at three different loading profiles (a triangular loading profile with peak loads
      of 600, 800 and 1000 MUN at loading/unloading rate of 60, 80 and 100 MUN/s,
      respectively; each test was 20s in duration). Significant differences were found
      for both the elastic modulus and hardness between the dry, moist and fully
      hydrated conditions (p<=0.02). For dry bone, elastic modulus and hardness values
      were not found to be significantly different between the different loading
      profiles (p>0.05). However, in both the moist and fully hydrated conditions, the
      elastic modulus and hardness were significantly different under all loading
      profiles (with the exception of the moist condition at the 600- and 800-MUN peak
      load). Given these findings, it is critical to perform nanoindentation of bone
      under fully hydrated conditions to ensure physiologically relevant results.
      Furthermore, this work found that a 20-s triangular loading/unloading profile was
      sufficient to capture the viscoelastic behavior of bone in the 600- to 1000-MUN
      peak load range. Lastly, specific peak load values and loading rates need to be
      selected based on the structural region for which the mechanical properties are
      to be measured.

PMID- 24094164
TI  - Preparation and characterization of bimodal porous poly(gamma-benzyl-L-glutamate)
      scaffolds for bone tissue engineering.
AB  - An ideal scaffold in bone tissue-engineering strategy should provide biomimetic
      extracellular matrix-like architecture and biological properties. Poly(gamma
      benzyl-L-glutamate) (PBLG) has been a popular model polypeptide for various
      potential biomedical applications due to its good biocompatibility and
      biodegradability. This study developed novel bimodal porous PBLG polypeptide
      scaffolds via a combination of biotemplating method and in situ ring-opening
      polymerization of gamma-benzyl-L-gIutamate N-carboxyanhydride (BLG-NCA). The PBLG
      scaffolds were characterized by proton nuclear magnetic resonance spectroscopy, X
      ray diffraction, differential scanning calorimetry, scanning electron microscope
      (SEM) and mechanical test. The results showed that the semi-crystalline PBLG
      scaffolds exhibited an anisotropic porous structure composed of honeycomb-like
      channels (100-200 MUm in diameter) and micropores (5-20 MUm), with a very high
      porosity of 97.4+/-1.6%. The compressive modulus and glass transition temperature
      were 402.8+/-20.6 kPa and 20.2 degrees C, respectively. The in vitro
      biocompatibility evaluation with MC3T3-E1 cells using SEM, fluorescent staining
      and MTT assay revealed that the PBLG scaffolds had good biocompatibility and
      favored cell attachment, spread and proliferation. Therefore, the bimodal porous
      polypeptide scaffolds are promising for bone tissue engineering.

PMID- 24094165
TI  - Laser surface modification of 316 L stainless steel with bioactive
      hydroxyapatite.
AB  - Laser-engineered net shaping (LENSTM), a commercial additive manufacturing
      process, was used to modify the surfaces of 316 L stainless steel with bioactive
      hydroxyapatite (HAP). The modified surfaces were characterized in terms of their
      microstructure, hardness and apatite forming ability. The results showed that
      with increase in laser energy input from 32 J/mm(2) to 59 J/mm(2) the thickness
      of the modified surface increased from 222+/-12 MUm to 355+/-6 MUm, while the
      average surface hardness decreased marginally from 403+/-18 HV0.3 to 372+/-8
      HV0.3. Microstructural studies showed that the modified surface consisted of
      austenite dendrites with HAP and some reaction products primarily occurring in
      the inter-dendritic regions. Finally, the surface-modified 316 L samples immersed
      in simulated body fluids showed significantly higher apatite precipitation
      compared to unmodified 316 L samples.

PMID- 24094166
TI  - Universal method for protein bioconjugation with nanocellulose scaffolds for
      increased cell adhesion.
AB  - Bacterial nanocellulose (BNC) is an emerging biomaterial since it is
      biocompatible, integrates well with host tissue and can be biosynthesized in
      desired architecture. However, being a hydrogel, it exhibits low affinity for
      cell attachment, which is crucial for the cellular fate process. To increase cell
      attachment, the surface of BNC scaffolds was modified with two proteins,
      fibronectin and collagen type I, using an effective bioconjugation method
      applying 1-cyano-4-dimethylaminopyridinium (CDAP) tetrafluoroborate as the
      intermediate catalytic agent. The effect of CDAP treatment on cell adhesion to
      the BNC surface is shown for human umbilical vein endothelial cells and the mouse
      mesenchymal stem cell line C3H10T1/2. In both cases, the surface modification
      increased the number of cells attached to the surfaces. In addition, the
      morphology of the cells indicated more healthy and viable cells. CDAP activation
      of bacterial nanocellulose is shown to be a convenient method to conjugate
      extracellular proteins to the scaffold surfaces. CDAP treatment can be performed
      in a short period of time in an aqueous environment under heterogeneous and mild
      conditions preserving the nanofibrillar network of cellulose. 

PMID- 24094167
TI  - Template-assisted electrohydrodynamic atomization of polycaprolactone for
      orthopedic patterning applications.
AB  - This paper presents the development of the novel deposition of biodegradable
      polycaprolactone (PCL) polymer patterns on a metallic substrate using a jet
      spraying technique, template-assisted electrohydrodynamic atomization (TAEA), at
      ambient temperature. The structure of patterns was controlled by systematically
      varying the polymer concentration (2-15 wt.%) and the flow rate (1-25 MUl min(
      1)). Polymer deposition was carried out in the stable cone-jet mode to precisely
      control the surface structure and morphology. The patterns were studied by
      optical microscopy, scanning electron microscopy and profilometry, and a high
      degree of control over the pattern geometry and thickness was achieved by varying
      the spraying time. The hardness and the effective elastic modulus of the polymer
      patterns were estimated using nanoindentation. The effect of load, loading rate
      and the holding time on the hardness and effective elastic modulus was derived.
      Optimal results were obtained with 5 wt.% PCL in DMAC solution sprayed within the
      stable cone-jet mode operating window at a flow rate of 15 MUl min(-1) for 300 s
      at 11.1 kV with a working distance of 60mm. Hexagonal patterns were well-defined
      and repeatable with thickness of ~34 MUm. The hardness is 1.6 MPa at a loading
      rate of 0.1 MUN/s and nearly halved when the load rate was increased to 1 MUN/s.
      The effective elastic modulus of ~12 MPa is obtained for a load rate of 0.1
      MUN/s.

PMID- 24094168
TI  - Boron nitride nanotubes coated with organic hydrophilic agents: stability and
      cytocompatibility studies.
AB  - In the present study, Boron Nitride Nanotubes (BNNTs) were synthesized and
      functionalized with organic hydrophilic agents constituted by glucosamine (GA),
      polyethylene glycol (PEG)1000, and chitosan (CH) forming new singular systems.
      Their size, distribution, and homogeneity were determined by photon correlation
      spectroscopy, while their surface charge was determined by laser Doppler
      anemometry. The morphology and structural organization were evaluated by
      Transmission Electron Microscopy. The functionalization was evaluated by
      Thermogravimetry analysis and Fourier Transformer Infrared Spectroscopy. The
      results showed that BNNTs were successfully obtained and functionalized, reaching
      a mean size and dispersity deemed adequate for in vitro studies. The in vitro
      stability tests also revealed a good adhesion of functionalized agents on BNNT
      surfaces. Finally, the in vitro cytocompatibility of functionalized BNNTs against
      MCR-5 cells was evaluated, and the results revealed that none of the different
      functionalization agents disturbed the propagation of normal cells up to the
      concentration of 50 MUg/mL. Furthermore, in this concentration, no significantly
      chromosomal or morphologic alterations or increase in ROS (Reactive Oxygen
      Species) could be observed. Thus, findings from the present study reveal an
      important stability and cytocompatibility of functionalized BNNTs as new
      potential drugs or radioisotope nanocarriers to be applied in therapeutic
      procedures.

PMID- 24094169
TI  - (Fe3O4)-graphene oxide as a novel magnetic nanomaterial for non-enzymatic
      determination of phenylalanine.
AB  - Fe3O4-graphene oxide (GO) modified glassy carbon (GC) electrode was used as a new
      magnetic nanosensor for determination of phenylalanine (Phe). It was found that
      Fe3O4-GO has been stably absorbed on GC electrode modified by simple technique.
      The cyclic voltammograms of the modified electrode in an aqueous solution
      displayed a pair of well-defined, stable and irreversible reductive/oxidation
      redox systems. The apparent electron transfer rate constant (k(s)) and transfer
      coefficient (alpha) were determined by cyclic voltammetry and were approximately
      9.3 s(-1) and 0.67, respectively. The modified electrode showed excellent
      catalytic activity towards the oxidation of Phe at an unusually positive
      potential in buffer solution. This nanosensor also displayed fast response time,
      high sensitivity, low detection limit and had a remarkably positive potential
      oxidation of Phe that decreased the effect of interferences in analysis.

PMID- 24094170
TI  - Injectable calcium phosphate-alginate-chitosan microencapsulated MC3T3-E1 cell
      paste for bone tissue engineering in vivo.
AB  - Osteoblasts or stem cells have been delivered into injectable calcium phosphate
      cement (CPC) to improve its effectiveness and biological function. However, the
      osteogenic potential of the new construct in vivo has been rarely reported, and
      there are no reports on alginate-chitosan microencapsulated osteoblasts mixed
      with CPC. This study aimed to develop alginate-chitosan microencapsulated mouse
      osteoblast MC3T3-E1 cells (AC-cells), evaluate the osteogenic potential of a
      calcium phosphate cement complex with these AC-cells (CPC-AC-cell), and trace the
      implanted MC3T3-E1 cells in vivo. MC3T3-E1 cells were embedded in alginate
      microcapsules, cultured in osteogenic medium for 7 days, and then covered with
      chitosan before mixing with a paste of beta-tricalcium phosphate/calcium
      phosphate cement (beta-TCP/CPC). The construct was injected into the dorsal
      subcutaneous area of nude mice. Lamellar-bone-like mineralization, newly formed
      collagen and angiogenesis were observed at 4 weeks. At 8 weeks, areas of newly
      formed collagen expanded; further absorption of beta-TCP/CPC and osteoid-like
      structures could be seen. Cell tracing in vivo showed that implanted MC3T3-E1
      cells were clearly visible at 2 weeks. These in vivo results indicate that the
      novel injectable CPC-AC-cell construct is promising for bone tissue engineering
      applications.

PMID- 24094171
TI  - Stem cell differentiation on electrospun nanofibrous substrates for vascular
      tissue engineering.
AB  - Nanotechnology has enabled the engineering of a variety of materials to meet the
      current challenges and requirements in vascular tissue regeneration. In our
      study, poly-L-lactide (PLLA) and hybrid PLLA/collagen (PLLA/Coll) nanofibers (3:1
      and 1:1) with fiber diameters of 210 to 430 nm were fabricated by
      electrospinning. Their morphological, chemical and mechanical characterizations
      were carried out using scanning electron microscopy (SEM), attenuated total
      reflectance Fourier transform infrared (ATR-FTIR), and tensile instrument,
      respectively. Bone marrow derived mesenchymal stem cells (MSCs) seeded on
      electrospun nanofibers that are capable of differentiating into vascular cells
      have great potential for repair of the vascular system. We investigated the
      potential of MSCs for vascular cell differentiation in vitro on electrospun
      PLLA/Coll nanofibrous scaffolds using endothelial differentiation media. After 20
      days of culture, MSC proliferation on PLLA/Coll(1:1) scaffolds was found 256%
      higher than the cell proliferation on PLLA scaffolds. SEM images showed that the
      MSC differentiated endothelial cells on PLLA/Coll scaffolds showed cobblestone
      morphology in comparison to the fibroblastic type of undifferentiated MSCs. The
      functionality of the cells in the presence of 'endothelial induction media', was
      further demonstrated from the immunocytochemical analysis, where the MSCs on
      PLLA/Coll (1:1) scaffolds differentiated to endothelial cells and expressed the
      endothelial cell specific proteins such as platelet endothelial cell adhesion
      molecule-1 (PECAM-1 or CD31) and Von Willebrand factor (vWF). From the results of
      the SEM analysis and protein expression studies, we concluded that the
      electrospun PLLA/Coll nanofibers could mimic the native vascular ECM environment
      and might be promising substrates for potential application towards vascular
      regeneration.

PMID- 24094172
TI  - Influence of PCL on the material properties of collagen based biocomposites and
      in vitro evaluation of drug release.
AB  - Formulation of biodegradable collagen-poly-epsilon-caprolactone (PCL) based
      biomaterials for the sustained release of insulin is the main objective of the
      present work. PCL has been employed to modulate the physico-chemical behavior of
      collagen to control the drug release. Designed formulations were employed to
      statistically optimize insulin release parameter profile at different collagen to
      PCL molar ratios. Circular dichroism, thermoporometry, FTIR, impedance and
      scanning electron microscopy techniques have been employed to investigate the
      effect of PCL on hydration dynamics of the collagen molecule, which in turn
      changes the dissolution parameters of the drug from the systems. Drug entrapment
      efficiency has been found to be maximum for collagen to PCL molar ratio of 1:2
      (>90%). In vitro dissolution test reveals that 99% of the drug was released from
      composite at collagen to PCL molar ratio of 1:3 and 1:4 within 2h, which
      indicates that hydrophobicity of the matrix results in weak interaction between
      lipophilic drug and carrier materials. The least burst release was observed for
      collagen to PCL molar ratio at 1:2 as synergistic interactions between collagen
      and PCL was maximum at that particular polymer-polymer ratios. The drug release
      data indicates super case-II transport of drug (n>1.0).

PMID- 24094173
TI  - Synthesis and characterization of PEG-iron oxide core-shell composite
      nanoparticles for thermal therapy.
AB  - In this study, core-shell nanoparticles were developed to achieve thermal therapy
      that can ablate cancer cells in a remotely controlled manner. The core-shell
      nanoparticles were prepared using atomic transfer radical polymerization (ATRP)
      to coat iron oxide (Fe3O4) nanoparticles with a poly(ethylene glycol) (PEG) based
      polymer shell. The iron oxide core allows for the remote heating of the particles
      in an alternating magnetic field (AMF). The coating of iron oxide with PEG was
      verified through Fourier transform infrared spectroscopy and thermal gravimetric
      analysis. A thermoablation (55 degrees C) study was performed on A549 lung
      carcinoma cells exposed to nanoparticles and over a 10 min AMF exposure. The
      successful thermoablation of A549 demonstrates the potential use of polymer
      coated particles for thermal therapy.

PMID- 24094174
TI  - Influence of carbides and microstructure of CoCrMo alloys on their metallic
      dissolution resistance.
AB  - CoCrMo alloys are passive and biocompatible materials widely used as joint
      replacements due to their good mechanical properties and corrosion resistance.
      Electrochemical behaviour of thermal treated CoCrMo alloys with different carbon
      content in their bulk alloy composition has been analysed. Both the amount of
      carbides in the CoCrMo alloys and the chemical composition of the simulated body
      fluid affect the electrochemical properties of these biomedical alloys, thus
      passive dissolution rate was influenced by the mentioned parameters. Lower
      percentage of carbon in the chemical composition of the bulk alloy and thermal
      treatments favour the homogenization of the surface (less amount of carbides),
      thus increasing the availability of Cr to form the oxide film and improving the
      corrosion resistance of the alloy. 

PMID- 24094175
TI  - Preparation of biomorphic porous calcium titanate and its application for
      preconcentration of nickel in water and food samples.
AB  - Biomorphic porous nanocrystalline-calcium titanate (SPCTO) was successfully
      prepared using the sol-gel method and with sorghum straw as the template.
      Characterization was conducted through XRD, SEM and FTIR. The ability of SPCTO to
      adsorb nickel ion in water was assessed. Elution and regeneration conditions, as
      well as the thermodynamics and kinetics of nickel adsorption, were also
      investigated. The result showed that the sorbent by the sol-gel template method
      was porous and has a perovskite structure with an average particle diameter of 26
      nm. The nickel ion could be quantitatively retained at a pH value range of 4-8,
      but the adsorbed nickel ion could be completely eluted using 2 mol L(-1) HNO3.
      The adsorption capacity of SPCTO for nickel was found to be 51.814 mg g(-1) and
      the adsorption behavior followed a Langmuir adsorption isotherm and a pseudo
      second-order kinetic model. The enthalpy change (DeltaH) of the adsorption
      process was 33.520 kJ mol(-1). At various temperatures, Gibbs free energy changes
      (DeltaG) were negative, and entropy changes (DeltaS) were positive. The
      activation energy (Ea) was 25.291 kJ mol(-1) for the adsorption. These results
      demonstrate that the adsorption was an endothermic and spontaneous physical
      process. This same method has been successfully applied in the preconcentration
      and determination of nickel in water and food samples with good results.

PMID- 24094176
TI  - Nanofiber density determines endothelial cell behavior on hydrogel matrix.
AB  - When cultured under static conditions, bacterial cellulose pellicles, by the
      nature of the polymer synthesis that involves molecular oxygen, are characterized
      by two distinct surface sides. The upper surface is denser in fibers (entangled)
      than the lower surface that shows greater surface porosity. Human umbilical vein
      endothelial cells (HUVECs) were used to exploit how the microarchitecture (i.e.,
      surface porosity, fiber network structure, surface topology, and fiber density)
      of bacterial cellulose pellicle surfaces influence cell-biomaterial interaction
      and therefore cell behavior. Adhesion, cell ingrowth, proliferation, viability
      and cell death mechanisms were evaluated on the two pellicle surface sides. Cell
      behavior, including secondary necrosis, is influenced only by the
      microarchitecture of the surface, since the biomaterial is extremely pure
      (constituted of cellulose and water only). Cell-cellulose fiber interaction is
      the determinant signal in the cell-biomaterial responses, isolated from other
      frequently present interferences such as protein and other chemical traces
      usually present in cell culture matrices. Our results suggest that
      microarchitecture of hydrogel materials might determine the performance of
      biomedical products, such as bacterial cellulose tissue engineering constructs
      (BCTECs). 

PMID- 24094177
TI  - Novel Ag@TiO2 nanocomposite synthesized by electrochemically active biofilm for
      nonenzymatic hydrogen peroxide sensor.
AB  - A novel nonenzymatic sensor for H2O2 was developed based on an Ag@TiO2
      nanocomposite synthesized using a simple and cost effective approach with an
      electrochemically active biofilm. The optical, structural, morphological and
      electrochemical properties of the as-prepared Ag@TiO2 nanocomposite were examined
      by UV-vis spectroscopy, X-ray diffraction, transmission electron microscopy and
      cyclic voltammetry (CV). The Ag@TiO2 nanocomposite was fabricated on a glassy
      carbon electrode (GCE) and their electrochemical performance was analyzed by CV,
      differential pulse voltammetry and electrochemical impedance spectroscopy. The
      Ag@TiO2 nanocomposite modified GCE (Ag@TiO2/GCE) displayed excellent performance
      towards H2O2 sensing at -0.73 V in the linear response range from 0.83 MUM to
      43.3 MUM, within a detection limit and sensitivity of 0.83 MUM and ~65.2328+/
      0.01 MUA MUM(-1) cm(-2), respectively. In addition, Ag@TiO2/GCE exhibited good
      operational reproducibility and long term stability.

PMID- 24094178
TI  - Stress analysis in bone tissue around single implants with different diameters
      and veneering materials: a 3-D finite element study.
AB  - The aim of this study was to evaluate the stress distribution on bone tissue with
      a single prosthesis supported by implants of large and conventional diameter and
      presenting different veneering materials using the 3-D finite element method.
      Sixteen models were fabricated to reproduce a bone block with implants, using two
      diameters (3.75*10 mm and 5.00*10 mm), four different veneering materials
      (composite resin, acrylic resin, porcelain, and NiCr crown), and two loads (axial
      (200 N) and oblique (100 N)). For data analysis, the maximum principal stress and
      von Mises criterion were used. For the axial load, the cortical bone in all
      models did not exhibit significant differences, and the trabecular bone presented
      higher tensile stress with reduced implant diameter. For the oblique load, the
      cortical bone presented a significant increase in tensile stress on the same side
      as the loading for smaller implant diameters. The trabecular bone showed a
      similar but more discreet trend. There was no difference in bone tissue with
      different veneering materials. The veneering material did not influence the
      stress distribution in the supporting tissues of single implant-supported
      prostheses. The large-diameter implants improved the transference of occlusal
      loads to bone tissue and decreased stress mainly under oblique loads. Oblique
      loading was more detrimental to distribution stresses than axial loading.

PMID- 24094179
TI  - Polydopamine as an intermediate layer for silver and hydroxyapatite
      immobilisation on metallic biomaterials surface.
AB  - Hydroxyapatite (HA) coated implant is more susceptible to bacterial infection as
      the micro-structure surface which is beneficial for osseointegration, could also
      become a reservoir for bacterial colonisation. The aim of this study was to
      introduce the antibacterial effect of silver (Ag) to the biomineralised HA by
      utilising a polydopamine film as an intermediate layer for Ag and HA
      immobilisation. Sufficient catechol groups in polydopamine were required to bind
      chemically stainless steel 316 L, Ag and HA elements. Different amounts of Ag
      nanoparticles were metallised on the polydopamine grafted stainless steel by
      varying the immersion time in silver nitrate solution from 12 to 24 h. Another
      polydopamine layer was then formed on the metallised film, followed by surface
      biomineralisation in 1.5 Simulated Body Fluid (SBF) solution for 3 days. Several
      characterisation techniques including X-Ray Photoelectron Spectroscopy, Atomic
      Force Microscopy, Scanning Electron Microscopy and Contact Angle showed that Ag
      nanoparticles and HA agglomerations were successfully immobilised on the
      polydopamine film through an element reduction process. The Ag metallisation at
      24 h has killed the viable bacteria with 97.88% of bactericidal ratio. The Ag was
      ionised up to 7 days which is crucial to prevent bacterial infection during the
      first stage of implant restoration. The aged functionalised films were considered
      stable due to less alteration of its chemical composition, surface roughness and
      wettability properties. The ability of the functionalised film to coat complex
      and micro scale metal make it suitable for dental and orthopaedic implants
      application.

PMID- 24094180
TI  - Visible light induced degradation of methylene blue using CeO2/V2O5 and CeO2/CuO
      catalysts.
AB  - In the present study, the nanocatalysts CeO2, V2O5, CuO, CeO2/V2O5 and CeO2/CuO
      were synthesized by thermal decomposition method. This method is simple, fast and
      cost effective compared with other preparation methods. The synthesized catalysts
      were characterized by different techniques. The XRD and XPS results confirmed the
      structure and the oxidization states of the nanocomposite materials. DRS results
      suggested that the prepared CeO2/V2O5 and CeO2/CuO nanocomposites can generate
      more electrons and holes under visible light irradiation. The photocatalytic
      activities of prepared catalysts were evaluated using the degradation of aqueous
      methylene blue solution as a model compound under visible light irradiation. In
      addition, the nanocomposite (CeO2/V2O5 and CeO2/CuO) materials were employed to
      degrade the textile effluent under visible light condition. 

PMID- 24094181
TI  - Preparation and characterization of sponge film made from feathers.
AB  - Feather wastes generated from poultry farms will pose a problem for disposal, but
      they are sustainable resources of keratin. Reduction is one of the commonly used
      methods to obtain soluble keratin from feather. However, the residues generated
      during feather reduction reaction were rarely investigated. In this study, the
      residues were transformed into a porous and flexible sponge film by freeze-drying
      without pretreatment or addition of cross-linking agents. Glycerol was used to
      alter the physical and chemical characteristics of the sponge film. The film was
      characterized with a fiber strong stretch instrument, a Fourier transform
      infrared spectrophotometer, scanning electron microscopy, an elemental analyzer,
      a differential scanning calorimeter and an automatic air permeability apparatus.
      Tensile strength and melting point of the sponge film with the optimum glycerol
      content were 6.2 MPa and 170 degrees C respectively. Due to air permeability of
      368 mm/s, the film can potentially be used in medicine, biology, textile,
      environmental technology, and so on. It is ecologically friendly and will produce
      additional benefits from the renewable materials. The film was utilized as
      adsorbents to remove Cr(VI) from aqueous solutions and as a filtering material
      for air pollution. Its maximum Cr(VI) uptake capacity was about 148.8 mg/g and
      the removal rate of PM10 was 98.3%.

PMID- 24094182
TI  - Enriched glucose and dextrin mannitol-based media modulates fibroblast behavior
      on bacterial cellulose membranes.
AB  - Bacterial cellulose (BC) produced by Gluconacetobacter hansenii is a suitable
      biopolymer for biomedical applications. In order to modulate the properties of BC
      and expand its use as substrate for tissue engineering mainly in the form of
      biomembranes, glucose or dextrin were added into a BC fermentation mannitol-based
      medium (BCGl and BCDe, respectively) under static culture conditions. SEM images
      showed effects on fiber density and porosity on both sides of the BC membranes.
      Both enriched media decreased the BET surface area, water holding capacity, and
      rehydration rate. Fourier transform infrared (attenuated total reflectance mode)
      spectroscopy (FTIR-ATR) analysis revealed no change in the chemical structure of
      BC. L929 fibroblast cells were seeded on all BC-based membranes and evaluated in
      aspects of cell adhesion, proliferation and morphology. BCG1 membranes showed the
      highest biological performance and hold promise for the use in tissue engineering
      applications. 

PMID- 24094183
TI  - Fabrication of Mg alloy tubes for biodegradable stent application.
AB  - Though Mg alloys are promising candidates for biodegradable stents, it is very
      difficult to fabricate stent tubes with high dimensional accuracy using Mg alloys
      because of their low deformability. This study aimed to develop thin-walled, high
      quality Mg alloy tubes with good performance in stent applications. Cold drawing
      with a fixed mandrel was carried out for extruded Mg-0.8%Ca and AZ61 alloy tubes
      using optimized drawing parameters and lubrication, and stent tubes with 1.5
      1.8mm outer diameter and 150 MUm thickness were fabricated. A dimensional
      evaluation showed that the tube dimensional errors were within 0.02-2.5%. Also,
      an immersion test of pure Mg with different crystal orientations showed that the
      crystal orientation affected the corrosion properties, results that are the same
      with other Mg alloys. The crystal orientation of the stent tube could be
      controlled by changing the deformation amount and direction in the drawing,
      showing that it is possible to further improve the biodegradability of stents by
      approaching their fabrication from a processing aspect.

PMID- 24094184
TI  - Hexadecylpyridinium surfactant modified zeolite A as an active component of a
      polymeric membrane sulfite selective electrode.
AB  - Zeolite A was synthesized from waste porcelain and modified by
      hexadecylpyridinium surfactant to change the cation exchanger property of the raw
      zeolite to anion exchanger property in the obtained surfactant modified zeolite
      (SMZ). The SMZ was used as an active ingredient component of a membrane selective
      sulfite electrode. The electrode was fully characterized in terms of composition,
      response time, thermal stability and usable pH range. The sensor showed suitable
      response to sulfite in the concentration range of 8.0*10(-7) to 1.0*10(-1) mol L(
      1), with a detection limit of 5.0*10(-7) mol L(-1) and a slope of -29.5+/-0.8 mV
      per decade of sulfite concentration.

PMID- 24094185
TI  - Wear behavior of light-cured resin composites with bimodal silica nanostructures
      as fillers.
AB  - To enhance wear behavior of resin composites, bimodal silica nanostructures
      including silica nanoparticles and silica nanoclusters were prepared and proposed
      as fillers. The silica nanoclusters, a combination of individually dispersed
      silica nanoparticles and their agglomerations, with size distribution of 0.07
      2.70 MUm, were fabricated by the coupling reaction between amino and epoxy
      functionalized silica nanoparticles, which were obtained by the surface
      modification of silica nanoparticles (~70 nm) using 3-aminopropyl triethoxysilane
      (APTES) and 3-glycidoxypropyl trimethoxysilane (GPS) as coupling agents,
      respectively. Silica nanoparticles and nanoclusters were then silanized with 3
      methacryloxypropyl trimethoxysilane (gamma-MPS) to prepare composites by mixing
      with bisphenol A glycerolate dimethacrylate (Bis-GMA) and tri (ethylene glycol)
      dimethacrylate (TEGDMA). Experimental composites with various filler compositions
      were prepared and their wear behaviors were assessed in this work. The results
      suggested that composites with increasing addition of silica nanoparticles in co
      fillers possessed lower wear volume and smoother worn surface. Particularly, the
      composite 53:17 with the optimum weight ratio of silica nanoparticles and silica
      nanoclusters presented the excellent wear behavior with respect to that of the
      commercial Esthet-X, although the smallest wear volume was achieved by Z350 XT.
      The introduction of bimodal silica nanostructures as fillers might provide a new
      sight for the design of resin composites with significantly improved wear
      resistance.

PMID- 24094186
TI  - Characterization of thermoplastic polyurethane/polylactic acid (TPU/PLA) tissue
      engineering scaffolds fabricated by microcellular injection molding.
AB  - Polylactic acid (PLA) and thermoplastic polyurethane (TPU) are two kinds of
      biocompatible and biodegradable polymers that can be used in biomedical
      applications. PLA has rigid mechanical properties while TPU possesses flexible
      mechanical properties. Blended TPU/PLA tissue engineering scaffolds at different
      ratios for tunable properties were fabricated via twin screw extrusion and
      microcellular injection molding techniques for the first time. Multiple test
      methods were used to characterize these materials. Fourier transform infrared
      spectroscopy (FTIR) confirmed the existence of the two components in the blends;
      differential scanning calorimetry (DSC) and dynamic mechanical analysis (DMA)
      confirmed the immiscibility between the TPU and PLA. Scanning electron microscopy
      (SEM) images verified that, at the composition ratios studied, PLA was dispersed
      as spheres or islands inside the TPU matrix and that this phase morphology
      further influenced the scaffold's microstructure and surface roughness. The
      blends exhibited a large range of mechanical properties that covered several
      human tissue requirements. 3T3 fibroblast cell culture showed that the scaffolds
      supported cell proliferation and migration properly. Most importantly, this study
      demonstrated the feasibility of mass producing biocompatible PLA/TPU scaffolds
      with tunable microstructures, surface roughnesses, and mechanical properties that
      have the potential to be used as artificial scaffolds in multiple tissue
      engineering applications. 

PMID- 24094187
TI  - Optimization strategies on the structural modeling of gelatin/chitosan scaffolds
      to mimic human meniscus tissue.
AB  - Meniscus lesions are frequently occurring injuries with poor ability to heal.
      Typical treatment procedure includes removal of damaged regions, which can lead
      to sub-optimal knee biomechanics and early onset of osteoarthritis. Some of the
      drawbacks of current treatment approach present an opportunity for a tissue
      engineering solution. In this study, gelatin (G)/chitosan (Cs) scaffolds were
      synthesized via gel casting method and cross-linked with naturally derived cross
      linker, genipin, through scaffold cross-linking method. Based on the
      characteristics of native meniscus tissue microstructure and function, three
      different layers were chosen to design the macroporous multilayered scaffolds.
      The multi-layered scaffolds were investigated for their ability to support human
      derived meniscus cells by evaluating their morphology and proliferation using MTT
      assay at various time points. Based on structural, mechanical and cell
      compatibility considerations, laminated scaffolds composed of G60/Cs40, G80/Cs20
      and G40/Cs60 samples, for the first, second and third layers, respectively, could
      be an appropriate combination for meniscus tissue engineering applications. 

PMID- 24094188
TI  - Enhanced mechanical properties of thermosensitive chitosan hydrogel by silk
      fibers for cartilage tissue engineering.
AB  - Articular cartilage has limited repair capability following traumatic injuries
      and current methods of treatment remain inefficient. Reconstructing cartilage
      provides a new way for cartilage repair and natural polymers are often used as
      scaffold because of their biocompatibility and biofunctionality. In this study,
      we added degummed chopped silk fibers and electrospun silk fibers to the
      thermosensitive chitosan/glycerophosphate hydrogels to reinforce two hydrogel
      constructs which were used as scaffold for hyaline cartilage regeneration. The
      gelation temperature and gelation time of hydrogel were analyzed by the rheometer
      and vial tilting method. Mechanical characterization was measured by uniaxial
      compression, indentation and dynamic mechanical analysis assay. Chondrocytes were
      then harvested from the knee joint of the New Zealand white rabbits and cultured
      in constructs. The cell proliferation, viability, production of
      glycosaminoglycans and collagen type II were assessed. The results showed that
      mechanical properties of the hydrogel were significantly enhanced when a hybrid
      with two layers of electrospun silk fibers was made. The results of GAG and
      collagen type II in cell-seeded scaffolds indicate support of the chondrogenic
      phenotype for chondrocytes with a significant increase in degummed silk fiber
      hydrogel composite for GAG content and in two-layer electrospun fiber-hydrogel
      composite for Col II. It was concluded that these two modified scaffolds could be
      employed for cartilage tissue engineering. 

PMID- 24094189
TI  - Effect of microstructure on the mechanical properties of as-cast Ti-Nb-Al-Cu-Ni
      alloys for biomedical application.
AB  - The correlation between the microstructure and mechanical behavior during tensile
      loading of Ti68.8Nb13.6Al6.5Cu6Ni5.1 and Ti71.8Nb14.1Al6.7Cu4Ni3.4 alloys was
      investigated. The present alloys were prepared by the non-equilibrium processing
      applying relatively high cooling rates. The microstructure consists of a
      dendritic bcc beta-Ti solid solution and fine intermetallic precipitates in the
      interdendritic region. The volume fraction of the intermetallic phases decreases
      significantly with slightly decreasing the Cu and Ni content. Consequently, the
      fracture mechanism in tension changes from cleavage to shear. This in turn
      strongly enhances the ductility of the alloy and as a result
      Ti71.8Nb14.1Al6.7Cu4Ni3.4 demonstrates a significant tensile ductility of about
      14% combined with the high yield strength of above 820 MPa already in the as-cast
      state. The results demonstrate that the control of precipitates can significantly
      enhance the ductility and yet maintaining the high strength and the low Young's
      modulus of these alloys. The achieved high bio performance (ratio of strength to
      Young's modulus) is comparable (or even superior) with that of the recently
      developed Ti-based biomedical alloys.

PMID- 24094190
TI  - The formulation and delivery of curcumin with solid lipid nanoparticles for the
      treatment of on non-small cell lung cancer both in vitro and in vivo.
AB  - Curcumin was determined to have anticancer potency on several kinds of carcinoma.
      However, its medical application was limited because of its poor bioavailability,
      unsatisfying dispersity and rapid metabolism in vivo. In this study, curcumin was
      delivered by solid lipid nanoparticles (SLN) for lung cancer treatment. The
      physiochemical characters of SLN-curcumin were detected by HPLC, TEM, Zeta
      potential analysis and FTIR, and the anticancer efficiency on lung cancer was
      determined both in vitro and in vivo. SLN-curcumin was synthesized by sol-gel
      method with the size ranged from 20 to 80 nm. After being loaded in SLN, the IC50
      of SLN-curcumin on A549 cells was 4 MUM, only 1/20 of plain drug. The plasmid
      concentration of curcumin was highly increased in mice via i.p. after loaded with
      SLN. Furthermore, SLN-curcumin enhanced the targeting of curcumin to lung and
      tumor, which finally increased the inhibition efficiency of curcumin from 19.5%
      to 69.3%. The Flow Cytometry (FCM) analysis and immuno staining confirmed that
      the inhibition effect mostly came from apoptosis, but not necrosis. The tumor
      targeting and profound tumor inhibition effect of SLN-curcumin indicated its
      medical application on lung cancer treatment, and also provided a novel method
      for new anticancer agents' development.

PMID- 24094191
TI  - In vivo optical detection of pH in microscopic tissue samples of Arabidopsis
      thaliana.
AB  - Minimally invasive in vivo measurement of pH in microscopic biological samples of
      MUm or MUl size, e.g. plant cells, tissues and saps, may help to explain complex
      biological processes. Consequently, techniques to achieve such measurements are a
      focus of interest for botanists. This paper describes a technique for the in vivo
      measurement of pH in the range pH5.0 to pH7.8 in microscopic plant tissue samples
      of Arabidopsis thaliana based on a ratiometric fluorescence method using low-loss
      robust tapered fiber probes. For this purpose tapered fiber probes were prepared
      and coated with a detection layer containing ion-paired fluorescent pH-transducer
      8-hydroxypyrene-1,3,6-trisulfonic acid trisodium salt (c-HPTS). A fluorescence
      ratiometric approach was employed based on excitation at 415 nm and 450 nm and on
      the comparison of the fluorescence response at 515 nm. The suitability of tapered
      fiber probes for local detection of pH between 5.0 and 7.8 was demonstrated. A pH
      sensitivity of 0.15 pH units was achieved within the pH ranges 5.0-5.9 and 7.1
      7.8, and this was improved to 0.04 pH units within the pH range 5.9-7.1. Spatial
      resolution of the probes was better than 20 MUm and a time response within 15-20s
      was achieved. Despite the minute dimensions of the tapered fiber probes the setup
      developed was relatively robust and compact in construction and performed
      reliably. It has been successfully employed for the in vivo local determination
      of pH of mechanically resistant plant tissues of A. thaliana of microscopic
      scale. The detection of momentary pH gradients across the intact plant seems to
      be a good tool for the determination of changes in pH in response to experimental
      treatments affecting for example enzyme activities, availability of mineral
      nutrients, hormonal control of plant development and plant responses to
      environmental cues.

PMID- 24094192
TI  - Influence of radiation crosslinked carboxymethyl-chitosan/gelatin hydrogel on
      cutaneous wound healing.
AB  - A series of carboxymethyl chitosan (CM-chitosan) and gelatin hydrogels were
      prepared by radiation crosslinking. A pre-clinical study was performed by
      implantation model and full-thickness cutaneous wound model in Sprague-Dawley
      rats to preliminarily evaluate the biocompatibility, biodegradability and effects
      on healing. In the implantation test, as a component of the hydrogels, CM
      chitosan showed a positive effect on promoting cell proliferation and
      neovascularization, while gelatin was efficient to stabilize the structure and
      prolong the degradation time. To evaluate the function on wound healing, the
      hydrogels were applied to the relatively large full-thickness cutaneous wounds
      (Phi3.0 cm). Compared with the control groups, the hydrogel group showed
      significantly higher percentage of wound closure on days 9, 12 and 15
      postoperatively, which was consistent with the significantly thicker granulation
      tissue on days 3 and 6. All results apparently revealed that the radiation
      crosslinked CM-chitosan/Gelatin hydrogels could induce granulation tissue
      formation and accelerate the wound healing.

PMID- 24094193
TI  - Post-processing of polymer foam tissue scaffolds with high power ultrasound: a
      route to increased pore interconnectivity, pore size and fluid transport.
AB  - The aim of this work is to demonstrate that the structural and fluidic properties
      of polymer foam tissue scaffolds, post-fabrication but prior to the introduction
      of cells, can be engineered via exposure to high power ultrasound. Our analysis
      is supported by measurements of fluid uptake during insonification and imaging of
      the scaffold microstructure via X-ray computed tomography, scanning electron
      microscopy and acoustic microscopy. The ultrasonic treatment is performed with a
      frequency of 30 kHz, average intensities up to 80,000 Wm(-2) and exposure times
      up to 20 h. The treatment is found to increase the mean pore size by over 10%.
      More striking is the improvement in fluid uptake: for scaffolds with only 40%
      water uptake via standard immersion techniques, we can routinely achieve full
      saturation of the scaffold over approximately one hour of exposure. These
      desirable modifications occur with negligible loss of scaffold integrity and
      mass, and are optimized when the ultrasound treatment is coupled to a pre-wetting
      stage with ethanol. Our findings suggest that high power ultrasound is highly
      targeted towards flow obstructions in the scaffold architecture, thereby
      providing an efficient means to promote pore interconnectivity and fluid
      transport in thick foam tissue scaffolds.

PMID- 24094194
TI  - Enhanced biocorrosion resistance and biocompatibility of degradable Mg-Nd-Zn-Zr
      alloy by brushite coating.
AB  - To further improve the corrosion resistance and biocompatibility of Mg-Nd-Zn-Zr
      alloy (JDBM), a biodegradable calcium phosphate coating (Ca-P coating) with high
      bonding strength was developed using a novel chemical deposition method. The main
      composition of the Ca-P coating was brushite (CaHPO4.2H2O). The bonding strength
      between the coating and the JDBM substrate was measured to be over 10 MPa, and
      the thickness of the coating layer was about 10-30 MUm. The in vitro corrosion
      tests indicated that the Ca-P treatment improved the corrosion resistance of JDBM
      alloy in Hank's solution. Ca-P treatment significantly reduced the hemolysis rate
      of JDBM alloy from 48% to 0.68%, and induced no toxicity to MC3T3-E1 cells. The
      in vivo implantation experiment in New Zealand's rabbit tibia showed that the
      degradation rate was reduced obviously by the Ca-P treatment and less gas was
      produced from Ca-P treated JDBM bone plates and screws in early stage of the
      implantation, and at least 10weeks degradation time can be prolonged by the
      present coating techniques. Both Ca-P treated and untreated JDBM Mg alloy induced
      bone growth. The primary results indicate that the present Ca-P treatment is a
      promising technique for the degradable Mg-based biomaterials for orthopedic
      applications.

PMID- 24094195
TI  - Purification of yeast alcohol dehydrogenase by using immobilized metal affinity
      cryogels.
AB  - In this study, poly(2-hydroxyethyl methacrylate-glycidylmethacrylate) [poly(HEMA
      GMA)] cryogels were prepared by radical cryocopolymerization of HEMA with GMA as
      a functional comonomer and N,N'-methylene-bisacrylamide (MBAAm) as a crosslinker.
      Iminodiacetic acid (IDA) functional groups were attached via ring opening of the
      epoxy group on the poly(HEMA-GMA) cryogels and then Zn(II) ions were chelated
      with these structures. Characterization of cryogels was performed by FTIR, SEM,
      EDX and swelling studies. These cryogels have interconnected pores of 30-50 MUm
      size. The equilibrium swelling degree of Zn(II) chelated poly(HEMA-GMA)-IDA
      cryogels was approximately 600%. Zn(II) chelated poly(HEMA-GMA)-IDA cryogels were
      used in the adsorption of alcohol dehydrogenase from aqueous solutions and
      adsorption was performed in continuous system. The effects of pH, alcohol
      dehydrogenase concentration, temperature, and flow rate on adsorption were
      investigated. The maximum amount of alcohol dehydrogenase adsorption was
      determined to be 9.94 mg/g cryogel at 1.0mg/mL alcohol dehydrogenase
      concentration and in acetate buffer at pH5.0 with a flow rate of 0.5 mL/min.
      Desorption of adsorbed alcohol dehydrogenase was carried out by using 1.0M NaCI
      at pH8.0 phosphate buffer and desorption yield was found to be 93.5%.
      Additionally, these cryogels were used for purification of alcohol dehydrogenase
      from yeast with a single-step. The purity of desorbed alcohol dehydrogenase was
      shown by silver-stained SDS-PAGE. This purification process can successfully be
      used for the purification of alcohol dehydrogenase from unclarified yeast
      homogenates and this work is the first report about the usage of the cryogels for
      purification of alcohol dehydrogenase.

PMID- 24094196
TI  - Fatigue behavior of porous biomaterials manufactured using selective laser
      melting.
AB  - Porous titanium alloys are considered promising bone-mimicking biomaterials.
      Additive manufacturing techniques such as selective laser melting allow for
      manufacturing of porous titanium structures with a precise design of micro
      architecture. The mechanical properties of selective laser melted porous titanium
      alloys with different designs of micro-architecture have been already studied and
      are shown to be in the range of mechanical properties of bone. However, the
      fatigue behavior of this biomaterial is not yet well understood. We studied the
      fatigue behavior of porous structures made of Ti6Al4V ELI powder using selective
      laser melting. Four different porous structures were manufactured with porosities
      between 68 and 84% and the fatigue S-N curves of these four porous structures
      were determined. The three-stage mechanism of fatigue failure of these porous
      structures is described and studied in detail. It was found that the absolute S-N
      curves of these four porous structures are very different. In general, given the
      same absolute stress level, the fatigue life is much shorter for more porous
      structures. However, the normalized fatigue S-N curves of these four structures
      were found to be very similar. A power law was fitted to all data points of the
      normalized S-N curves. It is shown that the measured data points conform to the
      fitted power law very well, R(2)=0.94. This power law may therefore help in
      estimating the fatigue life of porous structures for which no fatigue test data
      is available. It is also observed that the normalized endurance limit of all
      tested porous structures (<0.2) is lower than that of corresponding solid
      material (c.a. 0.4). 

PMID- 24094197
TI  - The production of volvox spheres and their potential application in multi-drugs
      encapsulation and release.
AB  - Volvox sphere is a bio-mimicking concept of an innovative biomaterial structure
      of a sphere that contains smaller microspheres which then encapsulate chemicals,
      drugs and/or cells. The volvox spheres were produced via a high-voltage
      electrostatic field system, using alginate as the primary material. Encapsulated
      materials tested in this study include staining dyes, nuclear fast red and trypan
      blue, and model drugs, bovine serum albumin (BSA) and cytochrome c (CytC). The
      external morphology of the volvox spheres was observed via electron microscopy
      whereas the internal structure of the volvox spheres was observed via an optical
      microscope with the aid of the staining dyes, since alginate is colorless and
      transparent. The diameter of the microspheres was about 200 to 300 MUm, whereas
      the diameter of the volvox spheres was about 1500 MUm. Volvox spheres were
      durable, retaining about 95% of their mass after 4 weeks. Factors affecting
      entrapment efficiency, such as temperature and concentration of the bivalent
      cross-linker, were compared followed by a 7-day in vitro release study. The
      encapsulation efficiency of CytC within the microspheres was higher at cold (~4
      degrees C) and warm (~50 degrees C) temperatures whereas temperature has no
      obvious effect on the BSA encapsulation. High crosslinking concentration (25%
      w/v) of calcium chloride has resulted higher entrapment efficiency for BSA but
      not for CytC. Furthermore, volvox spheres showed a different release pattern of
      BSA and CytC when compared to microspheres encapsulating BSA and CytC. Despite
      the fact that the mechanisms behind remain unclear and further investigation is
      required, this study demonstrates the potential of the volvox spheres for drug
      delivery.

PMID- 24094198
TI  - Spectrophotometric detection of histidine and lysine using combined enzymatic
      reactions.
AB  - An amino acid-sensing system with absorption spectrophotometric detection was
      developed. To ensure specific recognition of each amino acid, aminoacyl-tRNA
      synthetases were employed and the concentration of NADH produced by way of
      several enzymatic reactions was measured. Using this detection system, from 1.5
      to 55 MUM of histidine and from 15 to 95 MUM of lysine could be measured
      selectively in HEPES-KOH buffer (pH 8.0).

PMID- 24094199
TI  - Multifunctional porous titanium oxide coating with apatite forming ability and
      photocatalytic activity on a titanium substrate formed by plasma electrolytic
      oxidation.
AB  - Plasma electrolytic oxidation (PEO) was used to make a multifunctional porous
      titanium oxide (TiO2) coating on a titanium substrate. The key finding of this
      study is that a highly crystalline TiO2 coating can be made by performing the PEO
      in an ammonium acetate (CH3COONH4) solution; the PEO coating was formed by
      alternating between rapid heating by spark discharges and quenching in the
      solution. The high crystallinity of the TiO2 led to the surface having multiple
      functions, including apatite forming ability and photocatalytic activity.
      Hydroxyapatite formed on the PEO coating when it was soaked in simulated body
      fluid. The good apatite forming ability can be attributed to the high density of
      hydroxyl groups on the anatase and rutile phases in the coating. The degradation
      of methylene blue under ultraviolet radiation indicated that the coating had high
      photocatalytic activity. 

PMID- 24094200
TI  - Development of a modified electrode with amine-functionalized TiO2/multi-walled
      carbon nanotubes nanocomposite for electrochemical sensing of the atypical
      neuroleptic drug olanzapine.
AB  - In this work, using of amine-functionalized TiO2/multi-walled carbon nanotubes
      (NH2-TiO2-MWCNTs) nanocomposite for modification of glassy carbon electrode (GCE)
      was investigated. The nanocomposite was characterized by Fourier transformed
      infrared spectroscopy, transmission electron microscopy and scanning electron
      microscopy. The efficiency of modified electrode for electrocatalytic the
      oxidation of olanzapine was studied by cyclic voltammetry, square wave
      voltammetry and chronoamperometry. The electrochemical measurements were carried
      out in phosphate-buffered solution (PBS, pH 5.0). The NH2-TiO2-MWCNTs/GCE
      provided high surface area and more sensitive performance. The charge transfer
      coefficient (alpha) and the apparent charge transfer rate constant (k(s)) were
      calculated to be equal to 0.42 and 0.173 s(-1), respectively. The square wave
      voltammetry exhibited two linear dynamic ranges and a detection limit of 0.09 MUM
      of olanzapine. In addition, the modified electrode was employed for the
      determination of olanzapine in pharmaceutical and human blood serum samples in
      order to illustrate the applicability of proposed method.

PMID- 24094201
TI  - Voltammetric sensor based on carbon paste electrode modified with molecular
      imprinted polymer for determination of sulfadiazine in milk and human serum.
AB  - A new sensitive voltammetric sensor for determination of sulfadiazine is
      described. The developed sensor is based on carbon paste electrode modified with
      sulfadiazine imprinted polymer (MIP) as a recognition element. For comparison, a
      non-imprinted polymer (NIP) modified carbon paste electrode was prepared. Cyclic
      voltammetry (CV) and differential pulse voltammetry (DPV) methods were performed
      to study the binding event and electrochemical behavior of sulfadiazine at the
      modified carbon paste electrodes. The determination of sulfadiazine after its
      extraction onto the electrode surface was carried out by DPV at 0.92 V vs.
      Ag/AgCl owing to oxidation of sulfadiazine. Under the optimized operational
      conditions, the peak current obtained at the MIP modified carbon paste electrode
      was proportional to the sulfadiazine concentration within the range of 2.0*10(-7)
      1.0*10(-4) mol L(-1) with a detection limit and sensitivity of 1.4*10(-7) mol L(
      1) and 4.2*10(5) MUA L mol(-1), respectively. The reproducibility of the
      developed sensor in terms of relative standard deviation was 2.6%. The sensor was
      successfully applied for determination of sulfadiazine in spiked cow milk and
      human serum samples with recovery values in the range of 96.7-100.9%.

PMID- 24094203
TI  - Engineering polypyrrole nanotubes by 100 MeV Si9+ ion beam irradiation:
      enhancement of antioxidant activity.
AB  - In this work, the effect of 100 MeV Si(9+) ion beam with four different fluences
      on antioxidant and structural properties of polypyrrole nanotubes has been
      investigated. Polypyrrole nanotubes have been synthesized by reactive self
      degrade template method. Fragmentation of the polypyrrole nanotubes at higher
      fluence is revealed from the high resolution transmission electron micrograph
      (HRTEM) and X-ray diffraction (XRD) results. The decrease in characteristics band
      of polypyrrole in Fourier transmission of infrared spectra (FTIR) spectra
      suggests the main chain scission of polypyrrole during irradiation. The free
      radical scavenging activity of pristine and irradiated samples are evaluated by
      using alpha, alpha-diphenyl-beta-picrylhydrazyl (DPPH) assay. The decline of the
      UV-visible absorbance at 516 nm suggests the neutralization of DPPH free radicals
      through the reaction with polypyrrole. Significant increase in antioxidant
      activity of polypyrrole nanotubes is observed with increase in ion fluence.

PMID- 24094202
TI  - Subcritical CO2 sintering of microspheres of different polymeric materials to
      fabricate scaffolds for tissue engineering.
AB  - The aim of this study was to use CO2 at sub-critical pressures as a tool to
      sinter 3D, macroporous, microsphere-based scaffolds for bone and cartilage tissue
      engineering. Porous scaffolds composed of ~200 MUm microspheres of either
      poly(lactic-co-glycolic acid) (PLGA) or polycaprolactone (PCL) were prepared
      using dense phase CO2 sintering, which were seeded with rat bone marrow
      mesenchymal stromal cells (rBMSCs), and exposed to either osteogenic (PLGA, PCL)
      or chondrogenic (PLGA) conditions for 6 weeks. Under osteogenic conditions, the
      PLGA constructs produced over an order of magnitude more calcium than the PCL
      constructs, whereas the PCL constructs had far superior mechanical and structural
      integrity (125 times stiffer than PLGA constructs) at week 6, along with twice
      the cell content of the PLGA constructs. Chondrogenic cell performance was
      limited in PLGA constructs, perhaps as a result of the polymer degradation rate
      being too high. The current study represents the first long-term culture of CO2
      sintered microsphere-based scaffolds, and has established important thermodynamic
      differences in sintering between the selected formulations of PLGA and PCL, with
      the former requiring adjustment of pressure only, and the latter requiring the
      adjustment of both pressure and temperature. Based on more straightforward
      sintering conditions and more favorable cell performance, PLGA may be the
      material of choice for microspheres in a CO2 sintering application, although a
      different PLGA formulation with the encapsulation of growth factors,
      extracellular matrix-derived nanoparticles, and/or buffers in the microspheres
      may be advantageous for achieving a more superior cell performance than observed
      here.

PMID- 24094204
TI  - Electrospun composites of PHBV, silk fibroin and nano-hydroxyapatite for bone
      tissue engineering.
AB  - Electrospinning of fibrous scaffolds containing nano-hydroxyapatite (nHAp)
      embedded in a matrix of functional biomacromolecules offers an attractive route
      to mimicking the natural bone tissue architecture. Functional fibrous substrates
      will support cell attachment, proliferation and differentiation, while the role
      of HAp is to induce cells to secrete extracellular matrix (ECM) for
      mineralization to form bone. Electrospinning of biomaterials composed of
      polyhydroxybutyrate-co-(3-hydroxyvalerate) with 2% valerate fraction (PHBV), nano
      hydroxyapatite (nHAp), and Bombyx mori silk fibroin essence (SF), Mw=90KDa, has
      been achieved for nHAp and SF solution concentrations of 2 (w/vol) % each and 5
      (w/vol) % each. The structure and properties of the nanocomposite fibrous
      membranes were investigated by means of Scanning Electron Microscopy in
      combination with Energy Dispersive X-Ray Analysis (SEM/EDX), Fourier Transformed
      Infrared Spectroscopy (FT-IR), uniaxial tensile and compressive mechanical
      testing, degradation tests and in vitro bioactivity tests. SEM images showed
      smooth, uniform and continuous fibre deposition with no bead formation, and fibre
      diameters of between 10 and 15 MUm. EDX and FT-IR confirmed the presence of nHAp
      and SF. After one month in deionised water, tests showed less than 2% weight loss
      with the samples retaining their fibrous morphology, confirming that this
      material biodegrades slowly. After 28 days of immersion in Simulated Body Fluid
      (SBF) an apatite layer was visible on the surface of the fibres, proving their
      bioactivity. Preliminary in vitro biological assessment showed that after 1 and 3
      days in culture, cells were attached to the fibres, retaining their morphology
      while presenting a flattened appearance and elongated shape on the surface of
      fibres. Young's modulus was found to increase from 0.7 kPa (+/-0.33 kPa) for
      electrospun samples of PHBV only to 1.4 kPa (+/-0.54 kPa) for samples with 2
      (w/vol) % each of nHAp and SF. Samples prepared with 5 (w/vol) % each of nHAp and
      SF did not show a similar improvement.

PMID- 24094205
TI  - Improving the cellular invasion into PHEMA sponges by incorporation of the RGD
      peptide ligand: the use of copolymerization as a means to functionalize PHEMA
      sponges.
AB  - A monomer that contained the RGD ligand motif was synthesized and copolymerized
      with 2-hydroxyethyl methacrylate using polymerization-induced phase separation
      methods to form poly(2-hydroxyethyl methacrylate)-based hydrogel sponges. The
      sponges had morphologies of aggregated polymer droplets and interconnected pores,
      the pores having dimensions in the order of 10 MUm typical of PHEMA sponges. RGD
      containing moieties appeared to be evenly distributed through the polymer
      droplets. Compared to PHEMA sponges that were not functionalized with RGD, the
      new sponges containing RGD allowed greater invasion by human corneal epithelial
      cells, by advancing the attachment of cells to the surface of the polymer
      droplets.

PMID- 24094206
TI  - Curcumin containing monoolein aqueous dispersions: a preformulative study.
AB  - The present study describes the production and characterization of monoolein
      aqueous dispersions (MAD) as drug delivery systems for curcumin (CR). MAD based
      on monoolein and different emulsifiers have been produced and characterized.
      Morphology and dimensional distribution have been investigated by Cryogenic
      Transmission Electron Microscopy (cryo-TEM), X-ray and Photon Correlation
      Spectroscopy (PCS). Monoolein in different mixtures with sodium cholate, sodium
      caseinate, bentonite and poloxamer resulted in heterogeneous dispersions
      constituted of unilamellar vesicles, cubosomes and sponge type phases, depending
      on the employed components, as found by cryo-TEM and X-ray studies. CR was
      encapsulated with entrapment efficiencies depending on the MAD composition,
      particularly the highest was reached in the case of monoolein/poloxamer/sodium
      cholate mixture. The same mixture was able to maintain CR stability also after 6
      months. CR release modalities were in vitro investigated in order to mimic a
      possible subcutaneous administration of MAD. It was found that MAD constituted of
      monoolein/poloxamer and monoolein/poloxamer/sodium cholate mixtures were able to
      sustain CR release. MAD viscous vehicles were produced by xanthan gum. CR
      percutaneous absorption has been studied in vitro using excised human skin
      membranes [stratum corneum epidermis (SCE)] mounted into Franz cells. It was
      found that fluxes (Fn) of CR incorporated in MAD are influenced by the presence
      of monoolein based nanosystems. In particular xanthan gum based MAD better
      control CR diffusion from MAD.

PMID- 24094207
TI  - Fabrication of novel nanofiber scaffolds from gum tragacanth/poly(vinyl alcohol)
      for wound dressing application: in vitro evaluation and antibacterial properties.
AB  - Gum tragacanth (GT) is one of the most widely used natural gums which has found
      applications in many areas because of its attractive features such as
      biodegradability, nontoxic nature, natural availability, higher resistance to
      microbial attacks and long shelf-life properties. GT and poly(vinyl alcohol)
      (PVA) were dissolved in deionized water in different ratios i.e., 0/100, 30/70,
      60/40, 50/50, 40/60, 70/30, 0/100 mass ratio of GT/PVA. Nanofibers were produced
      from these solutions using electrospinning technique. The effect of different
      electrospinning parameters such as extrusion rate of polymer solutions, solution
      concentration, electrode spacing distance and applied voltage on the morphology
      of nanofibers was examined. The antibacterial activity of nanofibers and GT
      solution against Staphylococcus aureus and Pseudomonas aeruginosa was examined
      and these nanofibers showed good antibacterial property against Gram-negative
      bacteria. FTIR data showed that these two polymers may be having hydrogen bonding
      interactions. DSC data revealed that the exothermic peak at about 194 degrees C
      for PVA shifted to a lower temperature in GT/PVA blend. Human fibroblast cells
      adhered and proliferated well on the GT/PVA nanofiber scaffolds. MTT assay was
      carried out on the GT/PVA nanofiber to investigate the proliferation rate of
      fibroblast cells on the scaffolds. 

PMID- 24094208
TI  - Self-assembly into temperature dependent micro-/nano-aggregates of 5,10,15,20
      tetrakis(4-carboxyl phenyl)-porphyrin.
AB  - Various nanostructures of 5,10,15,20-tetrakis(4-carboxyl phenyl)-porphyrin
      (H2TCPP) can be easily synthesized by a surfactant-assisted self-assembly (SAS)
      method at different temperatures. When the DMF solution of porphyrin monomer was
      injected into cetyltimethylammonium bromide (CTAB) aqueous solution by a syringe,
      diverse H2TCPP nanostructures dependent on the different temperatures, including
      hollow nanospheres, solid nanospheres and nanospheres with holes, were
      successfully obtained. As a result, the suitable concentration of the CTAB
      aqueous solution used to form nanostructues of porphyrin ranges from 0.15 to 0.2
      mM. The various morphologies of porphyrin nanostructures were characterized by
      transmission electron microscopy (TEM), high resolution transmission electron
      microscopy (HRTEM) and scanning electron microscopy (SEM). UV-vis adsorption
      spectra showed that the micro-/nano-aggregate properties of porphyrin transformed
      from H-aggretates to J-aggregates during the process of self-assembly of
      porphyrin at different temperatures. Fluorescence spectra revealed a greater
      fluorescence quenching of various micro-/nano-aggregatess of porphyrin formed at
      different temperatures in aqueous solution, compared to the DMF solution of
      porphyrin monomer.

PMID- 24094209
TI  - Characterisation of micro-sized and nano-sized tungsten oxide-epoxy composites
      for radiation shielding of diagnostic X-rays.
AB  - Characteristics of X-ray transmissions were investigated for epoxy composites
      filled with 2-10 vol% WO3 loadings using synchrotron X-ray absorption
      spectroscopy (XAS) at 10-40 keV. The results obtained were used to determine the
      equivalent X-ray energies for the operating X-ray tube voltages of mammography
      and radiology machines. The results confirmed the superior attenuation ability of
      nano-sized WO3-epoxy composites in the energy range of 10-25 keV when compared to
      their micro-sized counterparts. However, at higher synchrotron radiation energies
      (i.e., 30-40 keV), the X-ray transmission characteristics were similar with no
      apparent size effect for both nano-sized and micro-sized WO3-epoxy composites.
      The equivalent X-ray energies for the operating X-ray tube voltages of the
      mammography unit (25-49 kV) were in the range of 15-25 keV. Similarly, for a
      radiology unit operating at 40-60 kV, the equivalent energy range was 25-40 keV,
      and for operating voltages greater than 60 kV (i.e., 70-100 kV), the equivalent
      energy was in excess of 40 keV. The mechanical properties of epoxy composites
      increased initially with an increase in the filler loading but a further increase
      in the WO3 loading resulted in deterioration of flexural strength, modulus and
      hardness.

PMID- 24094210
TI  - Kinetic characterization of the deproteinization of trabecular and cortical
      bovine femur bones.
AB  - The present study proposes an interpretation of the mechanism of bone
      deproteinization. Cortical and trabecular bovine femur bones were deproteinized
      using 6% NaOCl (37, 50, 60 degrees C). The kinetic parameters (rate constant and
      activation energy) were calculated, and the surface area of each type of bone was
      considered. A statistical analysis of the rate constants shows that cortical bone
      deproteinizes at a lower rate than trabecular. The activation energy is higher
      for trabecular than cortical bone, and no significant differences are found in
      the protein concentration values for both bones. Therefore, although trabecular
      bone deproteinizes at a higher rate than cortical, trabecular bone requires more
      energy for the deproteinization reaction to take place. Considering that both
      types of bones are constituted by mineral, protein, and water; the present work
      shows that the individual inner matrix architecture of trabecular and cortical
      bones, along with characteristics such as the mineral concentration and its
      bonding with collagen fibers, may be the responsible factors that control protein
      depletion. 

PMID- 24094211
TI  - Studies on the chemico-biological characteristics of bilirubin binding with
      collagen.
AB  - The clinical impact of bilirubin on collagen is investigated using various
      physical, chemical and biological methods. Thermo gravimetric analysis and
      differential scanning analysis of collagen-bilirubin complex matrices indicate
      that crosslinking does not alter their thermal behavior of collagen. The
      polydispersity of collagen-bilirubin complex increases in the reacting medium
      suggesting that there is an increase in the number of interacting points between
      them. Based on the zeta potential values, the rate of mobility of interacted
      complex decreases by inferring the extent of binding compared to the control
      collagen. Emission intensity begins to increase with increase in concentration of
      bilirubin which ascribes the conformational changes around the aromatic amino
      acids in collagen. Binding is indicated by an increase in resonance units and the
      responses are corrected by subtraction of those obtained for native collagen.
      Bilirubin showed a higher affinity for collagen at a concentration of about 25
      nM/mg. In this study, the association rate has been calculated which depicts the
      increased affinity of bilirubin to collagen. Affinity for bilirubin to collagen
      has been found to be 8.89*10(-3) s(-1). The greater part of binding of bilirubin
      to collagen is found to be electrostatic in nature. The investigation leads to
      comprehend the affinity of collagen-bilirubin complex during jaundice diseased
      tissues.

PMID- 24094212
TI  - A highly sensitive and selective electrochemical sensor for determination of
      Cr(VI) in the presence of Cr(III) using modified multi-walled carbon
      nanotubes/quercetin screen-printed electrode.
AB  - A novel screen-printed carbon electrode modified with quercetin/multi-walled
      carbon nanotubes was fabricated for determination of Cr(VI) in the presence of
      excess of Cr(III) without any pretreatment. The method is based on accumulation
      of the quercetin-Cr(III) complex generated in situ from Cr(VI) at the modified
      electrode surface in an open circuit followed by differential pulse voltammetry
      detection. The new method allowed selective determination of Cr(VI) in the
      presence of Cr(III). The influence of various parameters affecting the adsorptive
      stripping voltammetry performance was investigated. Under the optimum conditions,
      the calibration plot was found to be linear in the Cr(VI) concentration range
      from 1.0 to 200 MUmol(-1) with a limit of detection(S/N=3) of 0.3 MUmol L(-1).
      The relative standard deviation (RSD%) of seven replicates of the current
      measurements for a 50 MUmol(-1) of Cr(VI) solution was 3.0%. The developed
      electrode displayed a very low or no sensitivity to alkali, alkali-earth and
      transition metal cations and was successfully applied for the determination of
      Cr(VI) in drinking water samples.

PMID- 24094213
TI  - Nickel analysis in real samples by Ni2+ selective PVC membrane electrode based on
      a new Schiff base.
AB  - A newly synthesized Schiff base 3-aminoacetophenonesemicarbazone (AAS) has been
      used for the preparation of Ni(2+) selective PVC membrane electrode. The proposed
      electrode exhibits a Nernstian response over the nickel concentration range of
      1.0*10(-7) to 1.0*10(-2)mol L(-1) with a slope of 30.0+/-0.3 mV/decade of
      concentration. The limit of detection as determined from the intersection linear
      segment of the calibration plot is 5.1*10(-8) mol L(-1). The electrode shows good
      selectivity towards nickel with respect to several alkali, alkaline earth,
      transition and heavy metal ions. The response time of the electrode is very fast
      (>=10 s) and can be used for 17 weeks in the pH range of 2.0-9.8. The electrode
      can also be used in partially non-aqueous media having up to 20% (v/v) methanol,
      ethanol or acetone content with no significant change in the value of slope or
      working concentration range. To investigate the analytical applicability of the
      electrode, it was successfully applied as an indicator electrode in Ni(2+) ion
      potentiometric titration with EDTA, and in direct determination of nickel(II) in
      real samples.

PMID- 24094214
TI  - Influence of functionalized nanoparticles on conformational stability of type I
      collagen for possible biomedical applications.
AB  - Collagen-nanoparticle interactions are vital for many biomedical applications
      including drug delivery and tissue engineering applications. Iron oxide
      nanoparticles synthesized using starch template according to our earlier reported
      procedures were functionalized by treating them with Gum Arabic (GA), a
      biocompatible polysaccharide, so as to enhance the interaction between
      nanoparticle surfaces and collagen. Viscosity, circular dichroism (CD) and
      Fourier transform infrared spectroscopy (FTIR) techniques have been used to study
      the collagen-nanoparticle interactions. The relative viscosity for collagen
      nanoparticle conjugate was found to increase with increase in concentration of
      the nanoparticle within the concentration range investigated, which is due to the
      aggregation of protein onto the surface of nanoparticle. The CD spectra for the
      collagen-nanoparticle at different concentration ratios do not have much
      variation in the Rpn values (ratio of positive peak intensity over negative peak
      intensity) after functionalization with GA. The variation of molar ellipticity
      values for collagen-nanoparticle is due to the glycoprotein present in GA. The
      collagen triple helical structure is maintained after interaction with
      nanoparticles. The FTIR spectra of native collagen, Coll-Fs (nanoparticle without
      functionalization) and Coll-FsG (nanoparticle functionalized with GA) show
      clearly the amide I, II, III bands, with respect to collagen. The ability of
      polysaccharide stabilized/functionalized nanoparticles to maintain the collagen
      properties would help in its biomedical applications. 

PMID- 24094215
TI  - Influence of the microstructure on electrochemical corrosion and nickel release
      in NiTi orthodontic archwires.
AB  - The aim of this work was to determine the influence of the present phases and the
      chemical composition on the corrosion behavior and the nickel ion release of the
      NiTi orthodontic archwires. Eight Ni-Ti archwires from six commercial brands, in
      the as-received condition, were studied. The chemical composition, roughness,
      microstructure and the proportion of the phases as well as the corrosion behavior
      were analyzed for each archwire. The nickel ion release was characterized in
      artificial saliva immersion settings ranging up to 4 weeks. The results show that
      the presence of the martensitic phase improves corrosion resistance and
      significantly decreases Ni release into exterior medium in comparison with the
      austenitic specimens. In spite of the partial loss of superelasticity produced in
      the martensitic phase, it could be of great interest for biomedical applications,
      as it could minimize sensitization and allergies and improve biocompatibility and
      corrosion resistance of NiTi shape memory alloys.

PMID- 24094216
TI  - Polymer grafted hydroxyapatite whisker as a filler for dental composite resin
      with enhanced physical and mechanical properties.
AB  - The objective of this study was to investigate the effect of surface graft
      polymerization of hydroxyapatite whisker (HW) on physical and mechanical
      properties of dental composite resin. Poly bisphenol A glycidyl methacrylate
      (Poly(Bis-GMA)) was grafted onto silanized hydroxyapatite whisker (SHW) via
      solution polymerization and the amount of the Poly(Bis-GMA) on the surface was
      effectively controlled by polymerization time. The obtained poly(Bis-GMA) grafted
      hydroxyapatite whisker (PGHW) with different polymer contents was filled into a
      resin matrix respectively, meanwhile the composites with HW and with SHW served
      as controls. Monomer conversion was characterized by Fourier transform infrared
      spectroscopy (FTIR) and volume shrinkage of the composite resin was measured with
      a density tester. Mechanical properties were tested with a universal testing
      machine. The results indicated that the composite filled with PGHW-1h (graft
      ratio of poly(Bis-GMA): 8.5 wt.%) showed lower shrinkage and better mechanical
      properties, improving flexural strength by 6.5% and 11.9% compared with SHW
      filled composite and HW filled composite, respectively. However, PGHW with higher
      graft ratios aggregated seriously and formed defects in the composite, leading to
      deterioration of mechanical properties. It was revealed that the poly(Bis-GMA) on
      the surface of PGHW acted as a functional transition layer and enhanced
      interfacial compatibility and interaction between whisker and resin matrix, which
      facilitated the dispersion of PGHW in the composite and decreased the composite
      shrinkage. Thus, the graft polymerization of Bis-GMA on the surface of filler
      might be a promising modification method for the fabrication of dental materials.

PMID- 24094217
TI  - Preparation and in vitro evaluation of mesoporous hydroxyapatite coated beta-TCP
      porous scaffolds.
AB  - A mesoporous hydroxyapatite (HA) coating was prepared on a beta-tricalcium
      phosphate (beta-TCP) porous scaffold by a sol-gel dip-coating method using the
      block copolymer Pluronic F127 (EO106PO70EO106) as the template. For application
      as a bone graft, in vitro cell response and bone-related protein expression of
      mesoporous HA coated beta-TCP scaffold were investigated, using the non
      mesoporous HA coated scaffold as the control group, to evaluate the influence of
      the mesoporous structure on the biological properties of HA coating. It was found
      that the increased surface area of the mesoporous HA coating greatly affected the
      response of MC3T3-E1 osteoblasts and the expression of proteins. An enzyme-linked
      immunosorbent assay recorded a significantly higher expression of alkaline
      phosphatase (ALP) and bone sialoprotein (BSP) in the mesoporous group than those
      in the control group (*p<0.05) after different incubation periods. The
      introduction of mesopores enhanced the expression of ALP and BSP in the cells
      grown on the mesoporous HA coatings, on the premise of maintaining the protein
      expression in a sequence to ensure the correct temporo-spatial expression in
      osteogenesis. These results indicated that the mesoporous HA coating would
      provide a good environment for cell growth, suggesting that it could be used as
      the coating material for the surface modification of the tissue engineering
      scaffolds. 

PMID- 24094218
TI  - In vitro and in vivo antimicrobial properties of silver-containing hydroxyapatite
      prepared via ultrasonic spray pyrolysis route.
AB  - Hydroxyapatite (HAp), with its high biocompatibility and osteoconductivity,
      readily absorbs proteins, amino acids and other substances, which in turn favor
      the adsorption and colonization of bacteria. To prevent bacterial growth and
      biofilm formation on HAp discs, silver-containing (1-20 mol%) HAp (Ag-HAp)
      powders were synthesized using an ultrasonic spray pyrolysis (USSP) technique.
      The X-ray diffraction (XRD) peaks were very broad, indicating low crystallinity,
      and this induced the release of Ag(+) ions from Ag-HAp powders. In addition, a
      gradual increase in Ca(2+) ion release was observed. These results suggest that
      dissolution of Ca(2+) ion in Ag-HAp triggered the release of Ag(+) ions. The
      antimicrobial efficacy of Ag-HAp disc was tested against Staphylococcus aureus.
      Samples with Ag contents of more than 5 mol% were found to be highly effective
      against bacterial colonization and biofilm formation in vitro. In vivo
      antibacterial tests using bioluminescent strains also showed reductions in the
      viability of bacteria with Ag-HAp (5 mol%) discs. Biocompatibility tests using a
      modified Transwell(r) insert method showed that Ag-HAp (5 mol%) discs have
      negative effects on osteoblast proliferation. These results indicate that Ag-HAp
      (5 mol%) has effective antibacterial activity and good biocompatibility both in
      vitro and in vivo together with good biocompatibility, thus confirming its
      utility as a bactericidal material.

PMID- 24094219
TI  - In vitro metal ion release and biocompatibility of amorphous Mg67Zn28Ca5 alloy
      with/without gelatin coating.
AB  - Amorphous zinc-rich Mg-Zn-Ca alloys have exhibited good tissue compatibility and
      low hydrogen evolution in vivo. However, suboptimal cell-surface interaction on
      magnesium alloy surface observed in vitro could lead to reduced integration with
      host tissue for regenerative purpose. This study aims to improve cell-surface
      interaction of amorphous Mg67Zn28Ca5 alloy by coating a gelatin layer by
      electrospinning. Coated/uncoated alloys were immersed and extracted for 3 days
      under different CO2. The immersion results showed that pH and metal ion release
      in the alloy extracts were affected by gelatin coating and CO2, suggesting their
      roles in alloy biocorrosion and a mechanism has been proposed for the alloy-CO2
      system with/without coating. Cytotoxicity results are evident that gelatin-coated
      alloy with 2-day crosslinking not only exhibited no indirect cytotoxicity, but
      also supported attachment of L929 and MG63 cell lines around/on the alloy with
      high viability. Therefore, amorphous Mg67Zn28Ca5 alloy coated with gelatin by
      electrospinning technique provides a useful method to improve alloy
      biocompatibility.

PMID- 24094220
TI  - Electrochemical biosensing based on polypyrrole/titania nanotube hybrid.
AB  - The glucose oxidase (GOD) modified polypyrrole/titania nanotube enzyme electrode
      is fabricated for electrochemical biosensing application. The titania nanotube
      array is grown directly on a titanium substrate through an anodic oxidation
      process. A thin film of polypyrrole is coated onto titania nanotube array to form
      polypyrrole/titania nanotube hybrid through a normal pulse voltammetry process.
      GOD-polypyrrole/titania nanotube enzyme electrode is prepared by the covalent
      immobilization of GOD onto polypyrrole/titania nanotube hybrid via the cross
      linker of glutaraldehyde. The morphology and microstructure of nanotube
      electrodes are characterized by field emission scanning electron microscopy and
      Fourier transform infrared analysis. The biosensing properties of this nanotube
      enzyme electrode have been investigated by means of cyclic voltammetry and
      chronoamperometry. The hydrophilic polypyrrole/titania nanotube hybrid provides
      highly accessible nanochannels for GOD encapsulation, presenting good enzymatic
      affinity. As-formed GOD-polypyrrole/titania nanotube enzyme electrode well
      conducts bioelectrocatalytic oxidation of glucose, exhibiting a good biosensing
      performance with a high sensitivity, low detection limit and wide linear
      detection range. 

PMID- 24094221
TI  - Microstructure and mechanical properties of horns derived from three domestic
      bovines.
AB  - The microstructure and mechanical properties of horns derived from three domestic
      bovines (buffalo, cattle and sheep) were examined. The effects of water content,
      sampling position and orientation of three bovid horns on mechanical properties
      were systematically investigated by uniaxial tension and micron indentation
      tests. Meanwhile, the material composition and metal element contents were
      determined by Raman spectroscopy and elemental analysis respectively, and the
      microstructures of the horns were measured by scanning electron microscopy (SEM).
      Results show that the mechanical properties of horns have negative correlation
      with water contents and depend on sampling position and orientation. The spatial
      variations of the mechanical properties in horns are attributed to the different
      keratinization degrees in the proximal, middle and distal parts. And the
      mechanical properties of horns in the longitudinal direction are better than
      those in transverse. Among the three kinds of horns, the mechanical properties of
      buffalo horn are the best, followed by cattle horn, and those in sheep horn are
      the worst. This is due to the differences in material composition, metal element,
      and the microstructures of the horns. But the mechanical properties of buffalo
      horns are not dependent on the source of the buffalo. Therefore, regular
      engineered buffalo keratinous materials with standard mechanical properties can
      be obtained from different buffalo horns by using proper preparation methods. 

PMID- 24094222
TI  - Improving the corrosion resistance of Mg-4.0Zn-0.2Ca alloy by micro-arc
      oxidation.
AB  - In this paper, corrosion resistance of the Mg-4.0Zn-0.2Ca alloy was modified by
      micro-arc oxidation (MAO) process. The microstructure and phase constituents of
      MAO layer were characterized by SEM, XRD and X-ray photoelectron spectroscopy
      (XPS). The corrosion resistance of MAO treated Mg-4.0Zn-0.2Ca alloy in the
      simulated body fluid were characterized by potentiodynamic polarization and
      electrochemical impedance spectroscopy (EIS) techniques. The microstructure
      results indicated that a kind of ceramic film was composed by MgO and MgF2 was
      formed on the surface of Mg-4.0Zn-0.2Ca alloy after MAO treatment. The
      electrochemical test reveals that the corrosion resistance of MAO treated samples
      increase 1 order of magnitude. The mechanical intensity test showed that the MAO
      treated samples has suitable mechanical properties. 

PMID- 24094223
TI  - Preparation and characterization of keratin-based biocomposite hydrogels prepared
      by electron beam irradiation.
AB  - The biocompatible and highly porous keratin-based hydrogels were prepared using
      electron beam irradiation (EBI). The conditions for keratin-based hydrogel
      formation were investigated depending on several conditions, including the
      presence of poly(vinyl alcohol) (PVA), concentration of keratin solution, EBI
      dose, and poly(ethylene imine) (PEI) additives. The pure keratin (human hair and
      wool) aqueous solution was not gelled by EBI, while the aqueous keratin solutions
      blended with PVA were gelled at an EBI dose of more than 90 kGy. Furthermore, in
      the presence of PEI, the aqueous keratin solution blended with PVA could be
      gelled at a considerably lower EBI dose, even at 10 kGy. This finding suggests
      that the PEI additives significantly influence the rate of gelation and that PEIs
      function as an accelerator during gelation. The resulting keratin-based hydrogels
      were characterized using scanning electron microscopy (SEM), Fourier transform
      infrared spectroscopy (FT-IR), gel fraction, degree of swelling, gel strength,
      and kinetics of swelling analyses.

PMID- 24094224
TI  - Effect of raw material ratios on the compressive strength of magnesium potassium
      phosphate chemically bonded ceramics.
AB  - The compressive strength of magnesium potassium phosphate chemically bonded
      ceramics is important in biomedical field. In this work, the compressive strength
      of magnesium potassium phosphate chemically bonded ceramics was investigated with
      different liquid-to-solid and MgO-to-KH2PO4 ratios. X-ray diffractometer was
      applied to characterize its phase composition. The microstructure was imaged
      using a scanning electron microscope. The results showed that the compressive
      strength of the chemically bonded ceramics increased with the decrease of liquid
      to-solid ratio due to the change of the packing density and the crystallinity of
      hydrated product. However, with the increase of MgO-to-KH2PO4 weight ratio, its
      compressive strength increased firstly and then decreased. The low compressive
      strength in lower MgO-to-KH2PO4 ratio might be explained by the existence of the
      weak phase KH2PO4. However, the low value of compressive strength with the higher
      MgO-to-KH2PO4 ratio might be caused by lack of the joined phase in the hydrated
      product. Besides, it has been found that the microstructures were different in
      these two cases by the scanning electron microscope. Colloidal structure appeared
      for the samples with lower liquid-to-solid and higher MgO-to-KH2PO4 ratios
      possibly because of the existence of amorphous hydrated products. The
      optimization of both liquid-to-solid and MgO-to-KH2PO4 ratios was important to
      improve the compressive strength of magnesium potassium phosphate chemically
      bonded ceramics. 

PMID- 24094225
TI  - A new in vitro-in vivo correlation for bioabsorbable magnesium stents from
      mechanical behavior.
AB  - Correlating the in vitro and in vivo degradation of candidate materials for
      bioabsorbable implants is a subject of interest in the development of next
      generation metallic stents. In this study, pure magnesium wire samples were
      corroded both in the murine artery (in vivo) and in static cell culture media (in
      vitro), after which they were subjected to mechanical analysis by tensile
      testing. Wires corroded in vivo showed reductions in strength, elongation, and
      the work of fracture, with additional qualitative changes between tensile
      profiles. The in vivo degradation was 2.2+/-0.5, 3.1+/-0.8, and 2.3+/-0.3 times
      slower than corrosion in vitro in terms of effective tensile strength, strain to
      failure, and sample lifetime, respectively. Also, a combined metric, defined as
      strength multiplied by elongation, was 3.1+/-0.7 times faster in vitro than in
      vivo. Consideration of the utility and restrictions of each metric indicates that
      the lifetime-based multiplier is the best suited to general use for magnesium,
      though other metrics could be used to deduce the mechanical properties of
      degradable implants in service. 

PMID- 24094226
TI  - Mg-Al and Zn-Fe layered double hydroxides used for organic species storage and
      controlled release.
AB  - Layered double hydroxides (LDH) containing (Mg and Al) or (Zn and Fe) were
      prepared by coprecipitation at constant pH, using NaOH and urea as precipitation
      agents. The most pure LDH phase in the Zn/Fe system was obtained with urea and in
      Mg/Al system when using NaOH. The incorporation of phenyl-alanine (Phe) anions in
      the interlayer of the LDH was performed by direct coprecipitation, ionic exchange
      and structure reconstruction of the mixed oxide obtained by the calcination of
      the coprecipitated product at 400 degrees C. The reconstruction method and the
      direct coprecipitation in a medium containing Phe in the initial mixture were
      less successful in terms of high yields of organic-mineral composite than the
      ionic exchange method. A spectacular change in sample morphology and yield in
      exchanged solid was noticed for the Zn3Fe sample obtained by ionic exchange for
      6h with Phe solution. A delivery test in PBS of pH=7.4 showed the release of the
      Phe in several steps up to 25 h indicating different host-guest interactions
      between the Phe and the LDH matrix. This behavior makes the preparation useful to
      obtain late delivery drugs, by the incorporation of the anion inside the LDH
      layer.

PMID- 24094227
TI  - DNA adsorption characteristics of hollow spherule allophane nano-particles.
AB  - To understand the propensity of natural allophane to adsorb the DNA molecules,
      the adsorption characteristics were assessed against natural allophane (AK70),
      using single-stranded DNA (ss-DNA) and adenosine 5'-monophosphate (5'-AMP) as a
      reference molecule. The adsorption capacity of ss-DNA on AK70 exhibited one order
      of magnitude lower value as compared with that of 5'-AMP. The adsorption capacity
      of ss-DNA decreased with increasing pH due to the interaction generated between
      phosphate groups of ss-DNA and functional Al-OH groups on the wall perforations
      through deprotonating, associated with higher energy barrier for the adsorption
      of ss-DNA. The adsorption morphologies consisting of the individual ss-DNA with
      mono-layer coverage of the clustered allophane particle were observed
      successfully through transmission electron microscopy analysis. 

PMID- 24094228
TI  - Evidence of ammonium ion-exchange properties of natural bentonite and application
      to ammonium detection.
AB  - Ammonium exchange with hybrid PVC-bentonite (mineral montmorillonite clay) thin
      film was revealed using FTIR spectroscopy, EDX, cyclic voltammetry and
      electrochemical impedance spectroscopy. The effect of ammonium exchange on the
      charge transfer resistance of PVC-bentonite hybrid thin film was attributed to a
      modification of the intersheet distance and hydration of bentonite crystals. The
      obtained impedimetric ammonium sensor shows a linear range of detection from 10(
      4)M to 1M and a detection limit around 10(-6)M. 

PMID- 24094229
TI  - Arginine-responsive terbium luminescent hybrid sensors triggered by two crown
      ether carboxylic acids.
AB  - Crown ether carboxylic acids constitute main building blocks for the synthesis of
      terbium containing covalent cross-linked luminescent materials. Both the
      complexes and the hybrid nanomaterials could exhibit remarkable green emissions
      in pure water. More importantly, they were found to have a profound effect on the
      luminescence responses to arginine compared with glutamic acid, histidine,
      tryptophan, threonine, tyrosine and phenylalanine in aqueous environment. The
      present study provided the possibility of using a host-guest mechanism as a way
      of signal transduction based on lanthanide supramolecular hybrid materials. 

PMID- 24094230
TI  - pH-regulated release of dopamine from well-ordered self-assembled monolayers:
      electrochemical studies.
AB  - In the present work, gold electrode modified with novel aldehyde-terminated self
      assembled monolayers (SAMs) was used for controllable load and release of
      dopamine molecules by pH triggering. Electrochemical techniques including cyclic
      voltammetry (CV) and electrochemcial impedance spectroscopy (EIS) were employed
      to investigate the SAMs characteristic on the gold electrode surface. The
      electrochemical experiments indicated Faradaic behavior for the electrode surface
      after its modification with dopamine. Notably, it was observed that decreasing
      the conditioning pH, results in a decrease of peak currents, presumably due to
      the hydrolysis of the terminal imine bonds and releasing the dopamine moiety into
      the solution. Moreover, the preliminary kinetics studies were done for dopamine
      release from the SAMs surface as a model to design future drug delivery systems.
      Finally, the rate constant of dopamine release from the SAMs modified surface
      estimated to be 0.167 day(-1) at pH=3.

PMID- 24094231
TI  - Preclinical evaluation of strontium-containing bioactive bone cement.
AB  - Strontium (Sr) has become more attractive for orthopaedic applications as they
      can simultaneously stimulate bone formation and prevent bone loss. A Sr
      containing bioactive bone cement (Sr-BC) has been designed to fix osteoporotic
      bone fracture. Sr is a trace element, so the safety of containing Sr is concerned
      when Sr-BC is implanted in human body. The preclinical assessment of
      biocompatibility of Sr-BC was conducted according to ISO 10993 standards. MTT
      assay showed that this bioactive bone cement was non-toxic to mouse fibroblasts,
      and it met the basic requirement for the orthopaedic implant. The three
      independent genetic toxicity studies including Ames, chromosome aberration and
      bone marrow micronucleus assays demonstrated absence of genotoxic components in
      Sr-BC, which reassured the safety concerns of this novel bone cement. The muscle
      implantation results in present study were also encouraging. The acute
      inflammation around the cement was observed at 1 week post-implantation; however,
      no significant difference was observed between control and Sr-BC groups. These
      responses may be attributed to the presence of the foreign body, but the tissue
      healed after 12 weeks implantation. In summary, the above preclinical results
      provide additional assurance for the safety of this implant. Sr-BC can be used as
      a potential alternative to the traditional bone cement.

PMID- 24094232
TI  - In situ synthesized low modulus biomedical Zr-4Cu-xNb alloys.
AB  - In order to develop new biomaterials for hard tissue replacements, the Zr-4Cu-xNb
      (x=0, 0.3, 0.6 and 0.9) biomedical alloys with required properties were designed
      and prepared using vacuum arc melting method for the first time. Phase analysis
      and microstructure observation showed that all the as-cast Zr-4Cu-xNb samples
      consisted of alpha-Zr and Zr3Cu. In addition, the lamellar eutectoid is found
      near the grain boundary. These alloys exhibited moderate compressive strength
      (1150-1300 MPa), yield stress (750-1000 MPa), favorable plastic strain (19%-27%),
      high elastic energy (11 MJ/m(3)-16 MJ/m(3)) and low Young's modulus (25GPa
      31GPa). This good combination of mechanical properties indicates them potential
      biomedical materials for biological hard tissue replacements.

PMID- 24094233
TI  - The role of substrate morphology for the cytokine release profile of immature
      human primary macrophages.
AB  - There is increasing evidence that the physicochemical nature of any given
      material is a dominant factor for the release of cytokines by innate immune
      cells, specifically of macrophages, and thus majorly influences their interaction
      with other cell types. Recently, we could show that the 3D structure of star
      shaped polytheylene oxide-polypropylene oxide co-polymers (sP(EO-stat-PO))
      hydrogel coated substrates has a stronger influence on the release pattern of
      cytokines after 7 days of culture than surface chemistry. Here, we focused on the
      analysis of cytokine release over time and a more detailed analysis of cell
      morphology by scanning electron microscopy (SEM). Therefore, we compared
      different strategies for SEM sample preparation and found that using osmium
      tetroxide combined with aqua bidest led to best preparation results. For cytokine
      release we show significant changes from day 3 to day 7 of cell culture. After 3
      days, the sP(EO-stat-PO)-coated substrates led to an induction of pro-angiogenic
      CCL3 and CCL4, and of low amounts of the anti-inflammatory IL10, which declined
      at day 7. In contrast, pleiotropic IL6 and the pro-inflammatory TNFalpha and
      IL1beta were expressed stronger at day 7 than at day 3.

PMID- 24094234
TI  - Importance of isolated anti-hbc in detection of occult hepatitis B virus
      infection in hemodialysis patients.

PMID- 24094235
TI  - Thermal amplitude test.
AB  - The thermal amplitude test is performed to determine the reactivity of a cold
      autoantibody at varying temperatures: 4 degrees  C, 22 degrees  C, 30 degrees  C,
      and 37 degrees  C. Cold autoantibodies that are reactive at temperatures greater
      than 30 degrees  C have the potential to be clinically significant regardless of
      the antibody titer. Cold antibodies that are reactive at temperatures less than
      30 degrees  C are not considered to be clinically significant.

PMID- 24094236
TI  - Hemolytic disease of the fetus and newborn owing to anti-U, successfully treated
      with repeated intrauterine transfusions.
AB  - Hemolytic disease of the fetus and newborn (HDFN) owing to anti-U has rarely been
      reported. U is part of the MNS system.M and N glycoproteins are located on
      glycophorin A (GPA); Sand s antigens are on glycophorin B (GPB). Individuals who
      lack GPB are S- and s- and also lack U. The U- phenotype occurs almost
      exclusively in the African population and has a very low frequency (0.25%). Anti
      U is of immunoglobulin G class and can cause hemolytic transfusion reaction and
      HDFN. In this report we present the use of a noninvasive method to detect anemia
      in the fetus and the subsequent use of intrauterine transfusion(IUT) with blood
      of a very rare phenotype. For the first time, we used deglycerolized and 3-week
      old red blood cell units for IUT without signs of adverse reactions and with the
      expected effect on the hemoglobin value. We conclude that this transfusion
      strategy could be applied safely.

PMID- 24094237
TI  - Molecular analysis of patients with weak D and serologic analysis of those with
      anti-D (excluding type 1 and type 2).
AB  - Whether or not patients whose red blood cells (RBCs) carry certain weak D types
      produce anti-D, and if they do whether it is allo- or auto anti-D, remains
      controversial. The aim of this study was to determine the serologic features of
      anti-D in individuals expressing a weak D other than type 1 or type 2 and to
      assess whether the anti-D was an allo- or autoantibody. Serologic D typing and
      molecular analyses were performed on 748 individuals.Serologic characterization
      of anti-D included autologous controls,direct antiglobulin test, elution, and
      titration of anti-D before and after adsorption of serum onto autologous RBCs.
      From molecular analyses, 459 individuals exhibited a weak D type. We described
      seven novel RHD variant alleles. The most frequent types of weak D were type 1
      (30.1%), type 2 (23.7%), type 4.0 (10.2%), type 4.2.2(20.3%), type 11 (3.9%), and
      type 15 (3.7%). Anti-D was identified in the sera of 9 of 47 individuals with
      weak D type 4.0, in 14 of 93 with weak D type 4.2.2, in 1 of 18 with weak D type
      11, in 1 of 17 with weak D type 15, and in 1 weak D type 33 individual.Anti-D was
      demonstrated to be an alloantibody in weak D type 4.0, type 4.2.2, and type 15
      individuals, but an autoantibody in weak D type 11 and type 33 individuals. In
      conclusion, only a complete serologic investigation of individuals with a given
      weak D type identified by molecular analysis allows concluding on the nature of
      the antibody. Transfusing weak D type 4.2.2 and type 15 patients with D- RBC
      units and proposing anti-D immunoprophylaxis to women with these weak D types
      should be considered.

PMID- 24094238
TI  - A review of the JR blood group system.
AB  - The JR blood group system (ISBT 032) consists of one antigen,Jra, which is of
      high prevalence in all populations. The rare Jr(a-) phenotype has been found
      mostly in Japanese and other Asian populations, but also in people of northern
      European ancestry, in Bedouin Arabs, and in one Mexican. Anti-Jra has caused
      transfusion reactions and is involved in hemolytic disease of the fetus and
      newborn. The Jra antigen is located on ABCG2 transporter, a multipass membrane
      glycoprotein (also known as the breast cancer resistance protein, BCRP), which is
      encoded by the ABCG2 gene on chromosome 4q22.1. The Jr(a-) phenotype mostly
      results from recessive inheritance of ABCG2 null alleles caused by frameshift or
      nonsense changes.

PMID- 24094239
TI  - SC*994C>T causes the Sc(null) phenotype in Pacific Islanders and successful
      transfusion of Sc3+ blood to a patient with anti-Sc3.
AB  - Antigens in the SC blood group system are expressed by the human erythrocyte
      membrane-associated protein (ERMAP).Two molecular bases have been reported for
      the Sc,un phenotype:SC*307del2 and SC*994C>T. We report our investigation of the
      molecular background of five Sc,n1 individuals from the Pacific Islands and
      describe the successful transfusion of Sc3+ blood to a patient with anti-Sc3 in
      her plasma. SC (ERMAP) exons 2,3, and 12 and their flanking intronic regions were
      analyzed. TheSC*994C>T change introduces a restriction enzyme cleavage site for
      Tsp45I, and polymerase chain reaction (PCR) products from exon 12 were subjected
      to this PCR-restriction fragment length polymorphism (RFLP) assay. The five
      samples had the variant SC*994T/T. One sample, from a first cousin of one
      Marshallese proband, was heterozygous for SC*1514C/T (in the 3' untranslated
      region); the other four samples were SC*1514C/C(consensus sequence). Samples from
      white donors (n = 100) and African American donors (n = 99) were tested using the
      Tsp45IPCR-RFLP assay; all gave a banding pattern that was consistent with the
      SC*994C/C consensus sequence. In all five samples,our analyses showed
      homozygosity for the nonsense nucleotide change SC*994C>Tin an allele carrying
      the nucleotide associated with SLd. Further investigation determined that one of
      the probands reported previously with the SC*994C>T change was from the Marshall
      Islands (which form part of the Micronesian Pacific Islands) and the other was
      from an unspecified location within the large collection of Pacific Islands.
      Taken together, the five known probands with the SC*994C>T silencing nucleotide
      change were from the Pacific Islands.

PMID- 24094240
TI  - The Diego blood group system: a review.
AB  - The Diego blood group system (DI) currently encompasses 22 antigens. Three of the
      antigens are of high prevalence and the other 19 are of low prevalence. The
      antigens of the Diego blood group system are carried on the erythroid band 3
      protein anion exchanger 1 (AE1), the product of a single gene, SLC4A1 (solute
      carrier family 4, anion exchanger, member 1). AE1 is a member of a family of
      three anion exchangers or transporters expressed in a variety of tissues. This
      protein is involved in carbon dioxide transport from tissues to lungs. It is also
      found in the kidney,where it is involved in acid secretion. Antibodies to Diego
      system antigens with the exception of anti-Dia, -Dib, -Wra, -ELO and-DISK do not
      seem to be of clinical significance for transfusion or of importance in hemolytic
      disease of the fetus and newborn.

PMID- 24094241
TI  - Antipsychotic adherence patterns and health care utilization and costs among
      patients discharged after a schizophrenia-related hospitalization.
AB  - BACKGROUND: This study aimed to assess antipsychotic adherence patterns and all
      cause and schizophrenia-related health care utilization and costs sequentially
      during critical clinical periods (i.e., before and after schizophrenia-related
      hospitalization) among Medicaid-enrolled patients experiencing a schizophrenia
      related hospitalization. METHODS: All patients aged >= 18 years with a
      schizophrenia-related inpatient admission were identified from the MarketScan
      Medicaid database (2004-2008). Adherence (proportion of days covered [PDC]) to
      antipsychotics and schizophrenia-related and all-cause health care utilization
      and costs were assessed during preadmission (182- to 121-day, 120- to 61-day, and
      60- to 0-day periods; overall, 6 months) and postdischarge periods (0- to 60-day,
      61- to 120-day, 121- to 180-day, 181- to 240-day, 241- to 300-day, and 301- to
      365-day periods; overall, 12 months). Health care utilization and costs (2010 US
      dollars) were compared between each adjacent 60-day follow-up period after
      discharge using univariate and multivariable regression analyses. No adjustment
      was made for multiplicity. RESULTS: Of the 2,541 patients with schizophrenia
      (mean age: 41.2 years; 57% male; 59% black) who were identified, approximately
      89% were "discharged to home self-care." Compared with the 60- to 0-day period
      before the index inpatient admission, greater mean adherence as measured by PDC
      was observed during the 0- to 60-day period immediately following discharge (0.46
      vs. 0.78, respectively). The mean PDC during the overall 6-month preadmission
      period was lower than during the 6-month postdischarge period (0.53 vs. 0.69; P <
      0.001). Compared with the 0- to 60-day postdischarge period, schizophrenia
      related health care costs were significantly lower during the 61- to 120-day
      postdischarge period (mean: $2,708 vs. $2,102; P < 0.001); the primary cost
      drivers were rehospitalization (mean: $978 vs. $660; P < 0.001) and pharmacy
      (mean: $959 vs. $743; P < 0.001). Following the initial 60-day period, both all
      cause and schizophrenia-related costs declined and remained stable for the
      remaining postdischarge periods (days 121-365). CONCLUSIONS: Although long-term
      (e.g., 365-day) adherence measures are important, estimating adherence over
      shorter intervals may clarify the course of vulnerability to risk and enable
      clinicians to better design adherence/risk-related interventions. The greatest
      risk of rehospitalization and thus greater resource utilization were observed
      during the initial 60-day postdischarge period. Physicians should consider
      tailoring management and treatment strategies to help mitigate the economic and
      humanistic burden for patients with schizophrenia during this period.

PMID- 24094242
TI  - Genome-wide association study on serum alkaline phosphatase levels in a Chinese
      population.
AB  - BACKGROUND: Serum alkaline phosphatase (ALP) is a complex phenotype influenced by
      both genetic and environmental factors. Recent Genome-Wide Association Studies
      (GWAS) have identified several loci affecting ALP levels; however, such studies
      in Chinese populations are limited. We performed a GWAS analyzing the association
      between 658,288 autosomal SNPs and serum ALP in 1,461 subjects, and replicated
      the top SNPs in an additional 8,830 healthy Chinese Han individuals. The
      interactions between significant locus and environmental factors on serum ALP
      levels were further investigated. RESULTS: The association between ABO locus and
      serum ALP levels was replicated (P = 2.50 * 10-21, 1.12 * 10-56 and 2.82 * 10-27
      for SNP rs8176720, rs651007 and rs7025162 on ABO locus, respectively). SNP
      rs651007 accounted for 2.15% of the total variance of serum ALP levels
      independently of the other 2 SNPs. When comparing our findings with previously
      published studies, ethnic differences were observed across populations. A
      significant interaction between ABO rs651007 and overweight and obesity was
      observed (FDR for interaction was 0.036); for individuals with GG genotype, those
      with normal weight and those who were overweight or obese have similar serum ALP
      concentrations; minor allele A of rs651007 remarkably reduced serum ALP levels,
      but this effect was attenuated in overweight and obese individuals. CONCLUSIONS:
      Our findings indicate that ABO locus is a major determinant for serum ALP levels
      in Chinese Han population. Overweight and obesity modifies the effect of ABO
      locus on serum ALP concentrations.

PMID- 24094243
TI  - Hostile clinician behaviours in the nursing work environment and implications for
      patient care: a mixed-methods systematic review.
AB  - BACKGROUND: Although there is a sizeable body of evidence regarding the nature of
      hostile behaviours among clinicians in the nursing workplace, what is less clear
      is the nature of the relationship between these behaviours and patient care. To
      inform the development of appropriate intervention strategies we examine the
      level of evidence detailing the relationships between hostile clinician
      behaviours and patient care. METHODS: Published qualitative and quantitative
      studies that examined hostile clinician behaviours and patient care were
      included. Quality assessment, data extraction and analysis were undertaken on all
      included studies. The search strategy was undertaken in July and August 2011 and
      comprised eight electronic databases (CINAHL, Health Collection (Informit),
      Medline (Ovid), Ovid Nursing Full Text, Proquest Health and Medicine, PsycInfo,
      Pubmed and Cochrane library) as well as hand searching of reference lists.
      RESULTS: The search strategy yielded 30 appropriate publications. Employing
      content analysis four themes were refined: physician-nurse relations and patient
      care, nurse-nurse bullying, intimidation and patient care, reduced nurse
      performance related to exposure to hostile clinician behaviours, and nurses and
      physicians directly implicating patients in hostile clinician behaviours.
      CONCLUSIONS: Our results document evidence of various forms of hostile clinician
      behaviours which implicate nursing care and patient care. By identifying the
      place of nurse-nurse hostility in undermining patient care, we focus attention
      upon the limitations of policy and intervention strategies that have to date
      largely focused upon the disruptive behaviour of physicians. We conclude that the
      paucity of robustly designed studies indicates the problem is a comparatively
      under researched area warranting further examination.

PMID- 24094244
TI  - Isolation and characterization of neural stem cells from buffalo.
AB  - Neural stem cells (NSCs) are primordial, uncommitted cells postulated to give
      rise to the array of more specialized cells of the central nervous system (CNS).
      NSCs can self-renew and give rise to neurons, astrocytes and oligodendrocytes.
      NSCs are found in the CNS of mammalian organisms, and represent a promising
      resource for both fundamental research and CNS repair. Animal models of CNS
      damage have highlighted the potential benefit of NSC-based approaches. Present
      study described that buffalo neural stem cells (Bu-NSCs) were isolated and
      expanded rapidly from buffalo fetal brain in adherent culture. They were capable
      of multidifferentiation into neurons, astrocytes, and oligodendrocytes. Bu-NSCs
      were morphologically homogeneous and possessed high proliferation ability. The
      population doubled every 128.16 h. Normal buffalo karyotype was unchanged
      throughout the in vitro culture period. Together, we have isolated and cultured
      Bu-NSC from fetal brain that showed self-renewal, rapid proliferation and ability
      to differentiate into cells of nervous system. The availability of such cells may
      hold great interest for basic and applied neuroscience.

PMID- 24094245
TI  - PI3K/Akt pathway mediates Nrf2/ARE activation in human L02 hepatocytes exposed to
      low-concentration HBCDs.
AB  - We investigated the effects of hexabromocyclododecanes (HBCDs) at environmentally
      relevant concentrations on human L02 hepatocytes and explored possible underlying
      molecular mechanism(s), focusing on functional interactions between the
      phosphatidylinositol 3-kinase/protein kinase B (PI3K/Akt) and nuclear factor
      erythroid 2-related factor 2/antioxidant response element (Nrf2/ARE) pathways.
      The results showed that low concentrations of HBCDs could stimulate cell
      proliferation in a "DNA-dependent protein kinase catalytic subunit" (DNA-PKcs)
      dependent manner, increase protein levels and nuclear translocation of
      transcription factor Nrf2, and upregulate expression of its target gene heme
      oxygenase-1 (HO-1). Electrophoretic mobility-shift assays (EMSAs) showed that ARE
      was a prominent element for HO-1 induction after low-concentration HBCDs
      exposure. The relationship between PI3K/Akt pathway and Nrf2/HO-1 axis was
      demonstrated by the finding that pretreatment with PI3K inhibitors (wortmannin,
      LY294002) attenuated the upregulation of Nrf2 expression induced by HBCDs
      exposure. Furthermore, knock-down of DNA-PKcs through small interfering RNA
      blocked Nrf2/HO-1 axis activation in L02 cells exposed to low-concentration
      HBCDs. Moreover, DNA-PKcs and phosphorylated Akt at Ser(473) proved to be crucial
      in regulating the Nrf2-ARE pathway. Thus, the PI3K/Akt pathway is essential in
      regulating Nrf2-ARE pathway activation in L02 cells induced by low-concentration
      HBCDs. 

PMID- 24094246
TI  - Architecture, neurosurgery, urbanism, and "the city of seven billion".

PMID- 24094247
TI  - Surgery of the mind 2013: a kaleidoscopic landscape of disclosure, therapeutic
      need, and opportunity for progress.

PMID- 24094248
TI  - Functions of social support and self-verification in association with loneliness,
      depression, and stress.
AB  - This study investigated the influence of social support and self-verification on
      loneliness, depression, and stress among 477 college students. The authors
      propose and test a theoretical model using structural equation modeling. The
      results indicated empirical support for the model, with self-verification
      mediating the relation between social support and health outcomes. The results
      have implications for social support and self-verification research, which are
      discussed along with directions for future research and limitations of the study.

PMID- 24094251
TI  - Fluorescence enhancement upon G-quadruplex folding: synthesis, structure, and
      biophysical characterization of a dansyl/cyclodextrin-tagged thrombin binding
      aptamer.
AB  - A novel fluorescent thrombin binding aptamer (TBA), conjugated with the
      environmentally sensitive dansyl probe at the 3'-end and a beta-cyclodextrin
      residue at the 5'-end, has been efficiently synthesized exploiting Cu(I)
      catalyzed azide-alkyne cycloaddition procedures. Its conformation and stability
      in solution have been studied by an integrated approach, combining in-depth NMR,
      CD, fluorescence, and DSC studies. ITC measurements have allowed us to analyze in
      detail its interaction with human thrombin. All the collected data show that this
      bis-conjugated aptamer fully retains its G-quadruplex formation ability and
      thrombin recognition properties, with the terminal appendages only marginally
      interfering with the conformational behavior of TBA. Folding of this modified
      aptamer into the chairlike, antiparallel G-quadruplex structure, promoted by K(+)
      and/or thrombin binding, typical of TBA, is associated with a net fluorescence
      enhancement, due to encapsulation of dansyl, attached at the 3'-end, into the
      apolar cavity of the beta-cyclodextrin at the 5'-end. Overall, the structural
      characterization of this novel, bis-conjugated TBA fully demonstrates its
      potential as a diagnostic tool for thrombin recognition, also providing a useful
      basis for the design of suitable aptamer-based devices for theranostic
      applications, allowing simultaneously both detection and inhibition or modulation
      of the thrombin activity. 

PMID- 24094253
TI  - New dental standard required for AAHA accreditation.

PMID- 24094254
TI  - Letters to the editor: Home-prepared diets for dogs.

PMID- 24094255
TI  - What is your diagnosis? Carcinoma in a horse.

PMID- 24094256
TI  - ECG of the month. Sinus tachycardia due to albuterol-induced hypokalemia.

PMID- 24094257
TI  - Pathology in practice. Embryonal rhabdomyosarcoma in an alpaca.

PMID- 24094258
TI  - Pathology in practice. Thymoma in a parrot.

PMID- 24094259
TI  - Employment of female and male graduates of US veterinary medical colleges, 2013.

PMID- 24094260
TI  - Epidemiology of rabies in bats in Texas (2001-2010).
AB  - OBJECTIVE: To obtain epidemiological information on rabies in bats in Texas.
      DESIGN: Epidemiological study. SAMPLE: Laboratory reports of bats that had been
      submitted for rabies testing in Texas from 2001 through 2010. PROCEDURES:
      Laboratory reports were reviewed to obtain information on seasonality of rabies
      in bats; distribution, species, and rabies virus variants of rabid bats; and
      human and domestic animal exposures to rabid bats. RESULTS: The number of rabid
      bats during the first 5 years of the study period remained static until a > 2
      fold increase in 2006; during the subsequent 4 years, the annual number of rabid
      bats remained at this higher level, including a peak in 2008. The highest
      proportions of rabid bats were seen in late summer and early fall. The Brazilian
      free-tailed bat (Tadarida brasiliensis) was the most often affected species.
      Additionally, the rabies virus variant associated with the Brazilian free-tailed
      bat was the most prevalent. The percentage of rabid bats from urban areas was
      greater than that from rural areas. Dogs and cats were the domestic animals most
      frequently exposed to rabid bats. Most humans exposed to rabid bats did not
      report a known bite or scratch. The highest numbers of humans exposed to rabid
      bats were males between 11 to 15 years old. CONCLUSIONS AND CLINICAL RELEVANCE:
      Information on the epidemiology of rabies in bats and the epidemiology of
      exposures to rabid bats may be useful in planning and implementing local, state,
      and national rabies control and prevention campaigns and in encouraging rabies
      vaccination of domestic animals.

PMID- 24094261
TI  - Evaluation of risk factors associated with recurrent obstruction in cats treated
      medically for urethral obstruction.
AB  - OBJECTIVE: To determine risk factors for short-term recurrent urethral
      obstruction in cats after treatment by means of urinary catheterization and
      hospitalization. DESIGN: Prospective case series. ANIMALS: 83 client-owned cats.
      PROCEDURES: Physical examination findings, laboratory abnormalities, treatment
      decisions, and environmental changes were evaluated as risk factors for recurrent
      urethral obstruction in the 30 days following hospital discharge. RESULTS: Of the
      68 cats with completed follow-up surveys, 10 had an episode of recurrent urethral
      obstruction. Older cats were significantly more likely to have recurrent urethral
      obstruction. No specific laboratory abnormalities were associated with the risk
      of recurrent urethral obstruction. Longer duration of catheterization was
      significantly associated with a decreased risk of recurrent urethral obstruction.
      Duration of hospitalization and volume of IV fluids delivered were not
      significantly associated with recurrent urethral obstruction. Increasing water
      availability after discharge was associated with a decreased risk of recurrent
      urethral obstruction. There was no association between diet and recurrent
      urethral obstruction. CONCLUSIONS AND CLINICAL RELEVANCE: Results of this study
      suggested that longer duration of catheterization may be associated with a lower
      probability of short-term recurrent urethral obstruction in male cats. Older cats
      were at higher risk for recurrent obstruction. Owners should be encouraged to
      increase water availability after discharge in cats treated for urethral
      obstruction to decrease the likelihood of recurrence.

PMID- 24094262
TI  - Efficacy of two commercially available, low-magnesium, urine-acidifying dry foods
      for the dissolution of struvite uroliths in cats.
AB  - OBJECTIVE: To compare the efficacy and safety of using 2 commercially available,
      low-magnesium, urine-acidifying dry foods to dissolve sterile struvite uroliths
      in cats. DESIGN: Prospective, multicenter, randomized clinical trial . SAMPLE: 37
      cats with presumed struvite uroliths. PROCEDURES: Cats were randomly assigned to
      be fed 1 of 2 low-magnesium, urine-acidifying dry foods (food A or B). For each
      cat, physical examination, urinalysis, and abdominal radiography were performed
      weekly to assess treatment response. RESULTS: 32 cats had complete urolith
      dissolution. Mean +/- SD times for a 50% reduction in urolith size (0.69 +/- 0.1
      weeks) and complete urolith dissolution (13.0 +/- 2.6 days) were significantly
      shorter for cats fed food A, compared with those (1.75 +/- 0.27 weeks and 27.0 +/
      2.6 days, respectively) for cats fed food B. At study termination, mean +/- SD
      urine pH (6.083 +/- 0.105) for cats fed food A was lower than that (6.431 +/-
      0.109) for cats fed food B. In 5 cats, uroliths did not dissolve and were
      subsequently determined to be composed of 100% ammonium urate (n = 4) or 100%
      calcium oxalate (1). Adverse events associated with diet were not observed in any
      of the cats. CONCLUSIONS AND CLINICAL RELEVANCE: Results indicated that dietary
      dissolution is safe and effective for eradication of sterile struvite uroliths in
      cats. Cats fed food A had faster urolith dissolution than did cats fed food B.
      Lack of a reduction in urolith size at 2 weeks after diet initiation was
      indicative of misdiagnosis or noncompliance.

PMID- 24094263
TI  - Glargine insulin for treatment of naturally occurring diabetes mellitus in dogs.
AB  - OBJECTIVE: To evaluate the effects of twice-daily glargine insulin administration
      in dogs with diabetes mellitus. DESIGN: Open-label, prospective clinical trial.
      ANIMALS: 10 dogs with naturally occurring diabetes mellitus. PROCEDURES: Dogs
      with poorly regulated or newly diagnosed diabetes mellitus were enrolled if their
      owners agreed to return them to the hospital at 1- to 3-week intervals for 4
      follow-up visits. During each follow-up visit, blood glucose concentrations were
      measured every 2 hours for at least 10 hours after feeding a diet high in
      insoluble fiber and after administration of glargine insulin (time 0). The
      initial glargine insulin dosage was 0.5 U/kg (0.23 U/lb) SC twice daily. RESULTS:
      All dogs had well-regulated diabetes mellitus at a mean +/- SD of 38 +/- 14 days
      (median, 43 days; range, 7 to 55 days) following study enrollment. At the time
      diabetes mellitus was well regulated, mean glargine insulin dosage was 0.5 +/-
      0.15 U/kg (0.23 +/- 0.068 U/lb; median, 0.5 U/kg; range, 0.32 to 0.67 U/kg [0.15
      to 0.30 U/lb]) twice daily, and 3 dogs were receiving a dosage < 0.4 U/kg (0.18
      U/lb). In dogs with well-regulated diabetes mellitus, the mean minimum blood
      glucose concentration (163 +/- 89 mg/dL; 95% confidence interval, 100 to 227
      mg/dL) was detected 2 hours after administration of glargine insulin and the mean
      maximum blood glucose concentration (230 +/- 95 mg/dL; 95% confidence interval,
      64 to 323 mg/dL) was detected 12 hours after administration of glargine insulin.
      There was no significant difference between mean minimum and mean maximum blood
      glucose concentrations nor were there significant differences between blood
      glucose concentrations measured at other time points. Blood glucose concentration
      < 80 mg/dL was measured at least once in 7 of 10 dogs. CONCLUSIONS AND CLINICAL
      RELEVANCE: Results of the present study suggested that, in diabetic dogs fed a
      diet high in insoluble fiber, glargine insulin is a peakless insulin that does
      not induce a distinct blood glucose concentration nadir. For glargine insulin,
      0.3 U/kg (0.136 U/lb) SC twice daily is recommended as an initial dosage.

PMID- 24094264
TI  - Superficial digital flexor tendonitis in cutting horses: 19 cases (2007-2011).
AB  - OBJECTIVE: To characterize superficial digital flexor (SDF) tendon lesions in the
      forelimbs of cutting horses and determine recurrence rate and prognosis for this
      condition. DESIGN: Retrospective case series. ANIMALS: 19 cutting horses with SDF
      tendonitis. PROCEDURES: Medical records for horses evaluated for SDF tendonitis
      in 2007 through 2011 were reviewed. Data regarding age, sex, lameness grade,
      affected limb, and treatment were collected. Ultrasonographic images were
      reviewed, and lesion characteristics were recorded. Follow-up telephone
      interviews with owners or trainers were conducted to determine recurrence of SDF
      tendonitis, return of horse to its previous level of activity, and duration of
      the convalescent period. RESULTS: All 19 horses initially evaluated for SDF
      tendonitis had similar lesions in the lateral aspect of the tendon. The right
      forelimb was affected in 11 horses, and the left forelimb was affected in 7
      horses; 1 horse was affected in both forelimbs. Mean lameness grade was 1.26
      (range, 0 to 3). Of 17 horses for which follow-up information was available, 3
      had recurrence of tendon lesions and 1 developed a lesion in the contralateral
      forelimb SDF tendon; 16 horses returned to their previous level of activity.
      CONCLUSIONS AND CLINICAL RELEVANCE: The location of SDF tendonitis in cutting
      horses appeared to be unique in that no central core lesions were detected
      ultrasonographically. Lesions at the periphery of the tendon may have an
      increased ability to heal, compared with lesions at the central core. Results
      suggested that cutting horses with SDF tendonitis have a better prognosis than
      that reported for affected racehorses.

PMID- 24094265
TI  - Use of a hand-assisted laparoscopic surgical technique for closure of an
      extensive mesojejunal rent in a horse.
AB  - CASE DESCRIPTION: A 7-year-old 573-kg (1,261 -lb) Swiss Warmblood gelding was
      evaluated because of signs of acute abdominal pain. CLINICAL FINDINGS: Physical
      examination revealed a markedly distended abdomen with subjectively reduced
      borborygmi in all abdominal quadrants. A large, gas-distended viscus was present
      at the pelvic brim preventing complete palpation of the abdomen per rectum.
      Ultrasonographic evaluation could not be safely performed in the initial
      evaluation because of severe signs of abdominal pain. TREATMENT AND OUTCOME:
      Ventral midline celiotomy was performed, and right dorsal displacement of the
      ascending colon was corrected. Progressive signs of abdominal pain after surgery
      prompted repeat ventral midline celiotomy, and small intestinal incarceration in
      a large, radial mesojejunal rent was detected. The incarceration was reduced, but
      the defect was not fully accessible for repair via the celiotomy. Repair of the
      mesenteric defect was not attempted, and conservative management was planned
      after surgery; however, signs of colic returned. A standard laparoscopic approach
      was attempted from both flanks in the standing patient, but the small intestine
      could not be adequately mobilized for full evaluation of the rent. Hand-assisted
      laparoscopic surgery (HALS) allowed identification and reduction of jejunal
      incarceration and repair of the mesenteric rent. Although minor ventral midline
      incisional complications were encountered, the horse recovered fully. CLINICAL
      RELEVANCE: HALS techniques should be considered for repair of mesenteric rents in
      horses. In the horse of this report, HALS facilitated identification, evaluation,
      and repair of a large radial mesenteric rent that was not accessible from a
      ventral median celiotomy.

PMID- 24094266
TI  - Population pharmacokinetics of doxycycline in the tears and plasma of northern
      elephant seals (Mirounga angustirostris) following oral drug administration.
AB  - OBJECTIVE: To assess tear and plasma concentrations of doxycycline following oral
      administration to northern elephant seals (Mirounga angustirostris). DESIGN:
      Pharmacokinetic study. ANIMALS: 18 juvenile northern elephant seals without signs
      of ocular disease. PROCEDURES: Study seals were receiving no medications other
      than a multivitamin and were free from signs of ocular disease as assessed by an
      ophthalmic examination. Doxycycline (10 or 20 mg/kg [4.5 or 9.1 mg/lb]) was
      administered orally every 24 hours for 4 days. Tear and plasma samples were
      collected at fixed time points, and doxycycline concentration was assessed by
      means of liquid chromatography-tandem mass spectrometry. Concentration-time data
      were calculated via noncompartmental analysis. RESULTS: Following administration
      of doxycycline (10 mg/kg/d, PO), maximum plasma doxycycline concentration was 2.2
      MUg/mL at 6.1 hours on day 1 and was 1.5 MUg/mL at 4.0 hours on day 4.
      Administration of doxycycline (20 mg/kg/d, PO) produced a maximum plasma
      doxycycline concentration of 2.4 MUg/mL at 2.3 hours on day 1 and 1.9 MUg/mL at
      5.8 hours on day 4. Doxycycline elimination half-life on day 4 in animals
      receiving doxycycline at a dosage of 10 or 20 mg/kg/d was 6.7 or 5.6 hours,
      respectively. Mean plasma-to-tear doxycycline concentration ratios over all days
      were not significantly different between the low-dose (9.85) and high-dose (9.83)
      groups. For both groups, doxycycline was detectable in tears for at least 6 days
      following cessation of dosing. CONCLUSIONS AND CLINICAL RELEVANCE: Oral
      administration of doxycycline at the doses tested in the present study resulted
      in concentrations in the plasma and tears of northern elephant seals likely to be
      clinically effective for treatment of selected cases of systemic infectious
      disease, bacterial ulcerative keratitis, and ocular surface inflammation. This
      route of administration should be considered for treatment of corneal disease in
      northern elephant seals and possibly other related pinniped species.

PMID- 24094267
TI  - Clinical evaluation and biochemical analyses of thiamine deficiency in Pacific
      harbor seals (Phoca vitulina) maintained at a zoological facility.
AB  - OBJECTIVE: To determine thiamine-dependent enzyme activities in various tissue
      samples of Pacific harbor seals (Phoca vitulina) and thiaminase activities in
      dietary fish. DESIGN: Cross-sectional study. ANIMALS: 11 Pacific harbor seals
      with thiamine deficiency and 5 control seals. PROCEDURES: Seals underwent
      evaluation to rule out various diseases and exposure to toxins. For seals that
      died, measurement of thiamine-dependent enzymes in liver and brain samples and
      determination of mitochondrial DNA (mtDNA) copy number in liver, brain, and
      muscle samples were performed. Thiaminase activity in dietary fish was
      determined. RESULTS: 8 seals with thiamine deficiency died. Affected seals
      typically had acute neurologic signs with few nonspecific findings detected by
      means of clinicopathologic tests and histologic examination of tissue samples.
      Thiamine-dependent enzyme activities in liver samples of affected seals were
      significantly lower than those in control liver samples. The primary activation
      ratios and latencies for enzymes indicated that brain tissue was more affected by
      thiamine deficiency than liver tissue. Activities of pyruvate dehydrogenase were
      more affected by thiamine deficiency than those of transketolase and
      ketoglutarate dehydrogenase. For control seals, the mtDNA copy number in muscle
      samples was significantly lower than that for affected seals; conversely, the
      copy number in control liver samples was significantly greater than that of
      affected seals. Thiaminase activity was substantially higher in smelt than it was
      in other types of dietary fish. CONCLUSIONS AND CLINICAL RELEVANCE: Results of
      analyses in this study confirmed a diagnosis of thiamine deficiency for affected
      seals resulting from high thiaminase activity in dietary fish, inadequate vitamin
      administration, and increased thiamine demand caused by pregnancy and lactation.

PMID- 24094268
TI  - Effects of body position and extension of the neck and extremities on lung volume
      measured via computed tomography in red-eared slider turtles (Trachemys scripta
      elegans).
AB  - OBJECTIVE: To determine the effects of body position and extension of the neck
      and extremities on CT measurements of ventilated lung volume in red-eared slider
      turtles (Trachemys scripta elegans). DESIGN: Prospective crossover-design study.
      ANIMALS: 14 adult red-eared slider turtles. PROCEDURES: CT was performed on
      turtles in horizontal ventral recumbent and vertical left lateral recumbent,
      right lateral recumbent, and caudal recumbent body positions. In sedated turtles,
      evaluations were performed in horizontal ventral recumbent body position with and
      without extension of the neck and extremities. Lung volumes were estimated from
      helical CT images with commercial software. Effects of body position, extremity
      and neck extension, sedation, body weight, and sex on lung volume were analyzed.
      RESULTS: Mean +/- SD volume of dependent lung tissue was significantly decreased
      in vertical left lateral (18.97 +/- 14.65 mL), right lateral (24.59 +/- 19.16
      mL), and caudal (9.23 +/- 12.13 mL) recumbent positions, compared with the same
      region for turtles in horizontal ventral recumbency (48.52 +/- 20.08 mL, 50.66 +/
      18.08 mL, and 31.95 +/- 15.69 mL, respectively). Total lung volume did not
      differ among positions because of compensatory increases in nondependent lung
      tissue. Extension of the extremities and neck significantly increased total lung
      volume (127.94 +/- 35.53 mL), compared with that in turtles with the head, neck,
      and extremities withdrawn into the shell (103.24 +/- 40.13 mL). CONCLUSIONS AND
      CLINICAL RELEVANCE: Vertical positioning of red-eared sliders significantly
      affected lung volumes and could potentially affect interpretation of radiographs
      obtained in these positions. Extension of the extremities and neck resulted in
      the greatest total lung volume.

PMID- 24094269
TI  - Mitochondrial H2O2 as an enable signal for triggering autophosphorylation of
      insulin receptor in neurons.
AB  - BACKGROUND: Insulin receptors are widely distributed in the brain, where they
      play roles in synaptic function, memory formation, and neuroprotection.
      Autophosphorylation of the receptor in response to insulin stimulation is a
      critical step in receptor activation. In neurons, insulin stimulation leads to a
      rise in mitochondrial H2O2 production, which plays a role in receptor
      autophosphorylation. However, the kinetic characteristics of the H2O2 signal and
      its functional relationships with the insulin receptor during the
      autophosphorylation process in neurons remain unexplored to date. RESULTS:
      Experiments were carried out in culture of rat cerebellar granule neurons.
      Kinetic study showed that the insulin-induced H2O2 signal precedes receptor
      autophosphorylation and represents a single spike with a peak at 5-10 s and
      duration of less than 30 s. Mitochondrial complexes II and, to a lesser extent, I
      are involved in generation of the H2O2 signal. The mechanism by which insulin
      triggers the H2O2 signal involves modulation of succinate dehydrogenase activity.
      Insulin dose-response for receptor autophosphorylation is well described by
      hyperbolic function (Hill coefficient, nH, of 1.1+/-0.1; R2=0.99). N
      acetylcysteine (NAC), a scavenger of H2O2, dose-dependently inhibited receptor
      autophosphorylation. The observed dose response is highly sigmoidal (Hill
      coefficient, nH, of 8.0+/-2.3; R2=0.97), signifying that insulin receptor
      autophosphorylation is highly ultrasensitive to the H2O2 signal. These results
      suggest that autophosphorylation occurred as a gradual response to increasing
      insulin concentrations, only if the H2O2 signal exceeded a certain threshold.
      Both insulin-stimulated receptor autophosphorylation and H2O2 generation were
      inhibited by pertussis toxin, suggesting that a pertussis toxin-sensitive G
      protein may link the insulin receptor to the H2O2-generating system in neurons
      during the autophosphorylation process. CONCLUSIONS: In this study, we
      demonstrated for the first time that the receptor autophosphorylation occurs only
      if mitochondrial H2O2 signal exceeds a certain threshold. This finding provides
      novel insights into the mechanisms underlying neuronal response to insulin. The
      neuronal insulin receptor is activated if two conditions are met: 1) insulin
      binds to the receptor, and 2) the H2O2 signal surpasses a certain threshold,
      thus, enabling receptor autophosphorylation in all-or-nothing manner. Although
      the physiological rationale for this control remains to be determined, we propose
      that malfunction of mitochondrial H2O2 signaling may lead to the development of
      cerebral insulin resistance.

PMID- 24094270
TI  - Endoscopic and clinicopathological patterns of esophageal cancer in Tanzania:
      experiences from two tertiary health institutions.
AB  - BACKGROUND: Esophageal cancer is one of the most serious gastrointestinal cancer
      worldwide, owing to its rapid development and fatal prognoses in most cases.
      There is a paucity of published data regarding esophageal cancer in Tanzania and
      the study area in particular. This study was conducted to describe the endoscopic
      and clinicopathological patterns of esophageal cancer in this part of the world.
      The study provides baseline local data for future comparison. METHODS: This was a
      retrospective study of histologically confirmed cases of esophageal cancer seen
      at Bugando Medical Center and Muhimbili National Hospital between March 2008 and
      February 2013. Data were retrieved from medical record computer database and
      analyzed using SPSS computer software version 17.0. RESULTS: A total of 328
      esophageal cancer patients were enrolled in the study, representing 25.3% of all
      malignant gastrointestinal tract tumors. The male to female ratio was 2.2:1. The
      median age of patients at presentation was 47 years. The majority of patients
      (86.6%) were peasants coming from the rural areas. Smoking and alcohol
      consumption were documented in 74.7% and 61.6% of patients respectively. Family
      history of esophageal cancer was reported in 4.6% of cases. The majority of
      patients (81.7%) presented late with advanced stage of cancer. Progressive
      dysphagia and weight loss were the most common presenting symptoms occurring in
      all patients. The middle third esophagus (58.5%) was the most frequent anatomical
      site for esophageal cancer followed by lower third (27.4%) and upper third
      esophagus (10.4%). Squamous cell carcinoma (96.0%) was the most common
      histopathological type. Adenocarcinoma occurred in 13 (4.0%) patients. TNM
      staging was documented in only 104 (31.7%) patients. Of these, 102(98.1%)
      patients were diagnosed with advanced esophageal cancer (Stages III and IV).
      According to tumor grading, most of tumors were moderately differentiated
      accounting for 56.1% of cases. Distant metastasis was documented in 43.3% of
      patients. CONCLUSION: Esophageal cancer is not uncommon in this region and shows
      a trend towards a relative young age at presentation and the majority of patients
      present late with advanced stage. There is a need for screening of high-risk
      populations and detecting esophageal cancer at an early stage in order to improve
      chances for successful treatment and survival.

PMID- 24094271
TI  - Excited-state tautomerization of gas-phase cytosine.
AB  - In order to investigate experimentally observed phototautomerization of gas-phase
      cytosine, several excited-state tautomerization mechanisms were characterized at
      the EOM-CCSD and TDDFT levels. All pathways that took place exclusively on the S1
      surface were found to have significant barriers that were much higher than the
      barriers involved in radiationless decay of cytosine tautomers through conical
      intersections back to the ground state; tautomerization in this fashion cannot
      compete with radiationless relaxation. However, an alternative possibility is
      that the conical intersections that facilitate radiationless decay could also
      facilitate tautomerization. Barrierless pathways indicate that it is
      energetically possible that bifurcation at the conical intersections can lead to
      a subset of the population reaching different tautomers. This could be an
      explanation for the observed tautomerization of keto cytosine after exposure to
      low-energy UV light. 

PMID- 24094272
TI  - Child maltreatment deaths in the U.S. National Child Death Review Case Reporting
      System.
AB  - Comprehensive reviews of child death are increasingly conducted throughout the
      world, although limited information is available about how this information is
      systematically used to prevent future deaths. To address this need, we used cases
      from 2005 to 2009 in the U.S. National Child Death Review Case Reporting System
      to compare child and offender characteristics and to link that information with
      actions taken or recommended by review teams. Child, caretaker, and offender
      characteristics, and outcomes were compared to team responses, and findings were
      compared to published case series. Among 49,947 child deaths from 23 states
      entered into the Case Reporting System during the study period, there were 2,285
      cases in which child maltreatment caused or contributed to fatality. Over one
      half had neglect identified as the maltreatment, and 30% had abusive head trauma.
      Several child and offender characteristics were associated with specific
      maltreatment subtypes, and child death review teams recommended and/or planned
      several activities in their communities. Case characteristics were similar to
      those published in other reports of child maltreatment deaths. Teams implemented
      109 actions or strategies after their review, and we found that aggregating
      information from child death reviews offers important insights into understanding
      and preventing future deaths. The National Child Death Review Case Reporting
      System contains information about a large population which confirms and expands
      our knowledge about child maltreatment deaths and which can be used by
      communities for future action. 

PMID- 24094273
TI  - Clinical and laboratory characteristics of penicilliosis marneffei among patients
      with and without HIV infection in Northern Thailand: a retrospective study.
AB  - BACKGROUND: Penicilliosis marneffei is increasingly observed in individuals
      without HIV infection. This study aimed to compare the clinical and laboratory
      features among HIV infected and uninfected individuals with penicilliosis
      marneffei. METHODS: A retrospective cohort study was conducted between January 1,
      2007 and December 31, 2011 at Chiang Mai University Hospital. We included
      individuals who were >=15 years of age and presented with culture-proven P.
      marneffei infection. RESULTS: 116 HIV-infected and 34 HIV-uninfected patients
      were enrolled. Comparing to HIV-infected patients, HIV-uninfected patients were
      older; less likely to have fever, splenomegaly, and umbilicated skin lesions;
      more likely to have Sweet's syndrome and bone and joint infections; had higher
      white blood cell count, platelet count, and CD4 cell count; had lower alanine
      transaminase (ALT); and less likely to have positive fungal blood cultures. The
      mortality rates were 20.7% and 29.4% among HIV infected and uninfected patients,
      respectively. CONCLUSIONS: Clinical manifestations of penicilliosis marneffei are
      different between patients with and without HIV infection. Physician's awareness
      of this disease in HIV-uninfected patients may prompt the diagnosis and timely
      treatment, and can lead to a better outcome.

PMID- 24094275
TI  - Purification and characterization of a stable Kunitz trypsin inhibitor from
      Trigonella foenum-graecum (fenugreek) seeds.
AB  - Kunitz trypsin inhibitor was purified from the seeds of Trigonella foenum-graecum
      (TfgKTI) belonging to fabaceae family by ammonium sulphate precipitation, cation
      exchange, gel filtration and hydrophobic chromatography. Purity of the protein
      was analyzed by RP-HPLC and native-PAGE. SDS-PAGE analysis under reducing and non
      reducing conditions showed that protein consists of a single polypeptide chain
      with molecular mass of approximately 20 kDa. Mass spectroscopy analysis revealed
      that the intact mass of purified inhibitor is 19,842.154 Da. One dimensional SDS
      gel was tryptically digested, resulting peptides were subjected to MALDI-TOF-MS
      analysis, and peptide mass fingerprinting (PMF) analysis of TfgKTI shows sequence
      similarity with Kunitz trypsin inhibitor in database search. Two dimensional
      electrophoresis identified presence of four isoinhibitors (pI values of 5.1, 5.4,
      5.7 and 6.1). Kinetic studies showed that the protein is a competitive inhibitor
      and has high binding affinity with trypsin (Ki 3.01*10(-9)M) and chymotrypsin (Ki
      0.52*10(-9)M). The TfgKTI retained the inhibitory activity over a broad range of
      pH (pH 3-10), temperature (37-100 degrees C) and salt concentration (up to 3.5%).
      Far-UV circular dichroism measurements revealed that TfgKTI is predominantly
      composed of beta-sheets (39%) and unordered structures (48%) with slight helical
      content (13%). TfgKTI retained over 90% trypsin inhibition upon storage at 4
      degrees C for over a period of six months.

PMID- 24094274
TI  - Magnetic resonance imaging of a randomized controlled trial investigating
      predictors of recovery following psychological treatment in adolescents with
      moderate to severe unipolar depression: study protocol for Magnetic Resonance
      Improving Mood with Psychoanalytic and Cognitive Therapies (MR-IMPACT).
AB  - BACKGROUND: Major depressive disorders (MDD) are a debilitating and pervasive
      group of mental illnesses afflicting many millions of people resulting in the
      loss of 110 million working days and more than 2,500 suicides per annum.
      Adolescent MDD patients attending NHS clinics show high rates of recurrence into
      adult life. A meta-analysis of recent research shows that psychological
      treatments are not as efficacious as previously thought. Modest treatment
      outcomes of approximately 65% of cases responding suggest that aetiological and
      clinical heterogeneity may hamper the better use of existing therapies and
      discovery of more effective treatments. Information with respect to optimal
      treatment choice for individuals is lacking, with no validated biomarkers to aid
      therapeutic decision-making. METHODS/DESIGN: Magnetic resonance-Improving Mood
      with Psychoanalytic and Cognitive Therapies, the MR-IMPACT study, plans to
      identify brain regions implicated in the pathophysiology of depressions and
      examine whether there are specific behavioural or neural markers predicting
      remission and/or subsequent relapse in a subsample of depressed adolescents
      recruited to the IMPACT randomised controlled trial (Registration #
      ISRCTN83033550). DISCUSSION: MR-IMPACT is an investigative biomarker component of
      the IMPACT pragmatic effectiveness trial. The aim of this investigation is to
      identify neural markers and regional indicators of the pathophysiology of and
      treatment response for MDD in adolescents. We anticipate that these data may
      enable more targeted treatment delivery by identifying those patients who may be
      optimal candidates for therapeutic response. TRIAL REGISTRATION: Adjunctive study
      to IMPACT trial (Current Controlled Trials: ISRCTN83033550).

PMID- 24094276
TI  - Prevalence and determinants of obesity among primary school children in Dar es
      Salaam, Tanzania.
AB  - BACKGROUND: Childhood obesity has increased dramatically and has become a public
      health concern worldwide. Childhood obesity is likely to persist through
      adulthood and may lead to early onset of NCDs. However, there is paucity of data
      on obesity among primary school children in Tanzania. This study assessed the
      prevalence and determinants of obesity among primary school children in Dar es
      Salaam. METHODS: A cross sectional study was conducted among school age children
      in randomly selected schools in Dar es Salaam. Anthropometric and blood pressure
      measurements were taken using standard procedures. Body Mass Index (BMI) was
      calculated as weight in kilograms divided by the square of height in meters
      (kg/m2). Child obesity was defined as BMI at or above 95th percentile for age and
      sex. Socio-demographic characteristics of children were determined using a
      structured questionnaire. Logistic regression was used to determine association
      between independent variables with obesity among primary school children in Dar
      es Salaam. RESULTS: A total of 446 children were included in the analysis. The
      mean age of the participants was 11.1+/-2.0 years and 53.1% were girls. The mean
      BMI, SBP and DBP were 16.6+/-4.0 kg/m2, 103.9+/-10.3mmHg and 65.6+/-8.2mmHg
      respectively. The overall prevalence of child obesity was 5.2% and was higher
      among girls (6.3%) compared to boys (3.8%). Obese children had significantly
      higher mean values for age (p=0.042), systolic and diastolic blood pressures (all
      p<0.001). Most obese children were from households with fewer children (p=0.019)
      and residing in urban areas (p=0.002). Controlling for other variables, age above
      10 years (AOR=3.3, 95% CI=1.5-7.2), female sex (AOR=2.6, 95% CI=1.4-4.9), urban
      residence (AOR=2.5, 95% CI=1.2-5.3) and having money to spend at school (AOR=2.6,
      95% CI=1.4-4.8) were significantly associated with child obesity. CONCLUSIONS:
      The prevalence of childhood obesity in this population was found to be low.
      However, children from urban schools and girls were proportionately more obese
      compared to their counterparts. Primary preventive measures for childhood obesity
      should start early in childhood and address socioeconomic factors of parents
      contributing to childhood obesity.

PMID- 24094277
TI  - On applying cognitive psychology.
AB  - Recent attempts to assess the practical impact of scientific research prompted my
      own reflections on over 40 years worth of combining basic and applied cognitive
      psychology. Examples are drawn principally from the study of memory disorders,
      but also include applications to the assessment of attention, reading, and
      intelligence. The most striking conclusion concerns the many years it typically
      takes to go from an initial study, to the final practical outcome. Although the
      complexity and sheer timescale involved make external evaluation problematic, the
      combination of practical satisfaction and theoretical stimulation make the
      attempt to combine basic and applied research very rewarding.

PMID- 24094278
TI  - Need for closure and heuristic information processing: the moderating role of the
      ability to achieve the need for closure.
AB  - In contrast to the ample research that shows a positive relationship between the
      need for closure (NFC) and heuristic information processing, this research
      examines the hypothesis that this relationship is moderated by the ability to
      achieve closure (AAC), that is, the ability to use information-processing
      strategies consistent with the level of NFC. Three different operationalizations
      of heuristic information processing were used: recall of information consistent
      with the impression (Study 1); pre-decisional information search (Study 2); and
      stereotypic impression formation (Study 3). The results of the studies showed
      that there were positive relationships between NFC and heuristic information
      processing when participants assessed themselves as being able to use cognitive
      strategies consistent with their level of NFC (high AAC). For individuals with
      low AAC, the relationships were negative. Our data show that motivation-cognition
      interactions influence the information-processing style. 

PMID- 24094279
TI  - Agreeableness, conscientiousness, and psychoticism: distinctive influences of
      three personality dimensions in adolescence.
AB  - Researchers have suggested that the psychoticism (P) personality dimension of the
      Eysenck Personality Questionnaire may be largely redundant with the agreeableness
      (A) and conscientiousness (C) constructs of the five-factor model. Little
      research has examined the distinctiveness of these constructs. We utilized a
      multi-wave, multi-method design to examine the ability of C, A, and P to uniquely
      predict a number of important outcomes amongst high school students. A total of
      778 students (391 males, 387 females; mean age 15.41 years.) completed
      personality measures in Grade 10. Self-reported self-esteem, social support,
      health-related behaviours, religious values as well as teachers' assessments of
      students, were collected 1 and 2 years later. A, C, and P were distinctive in
      their ability to predict these outcomes, after controlling for gender and socio
      economic status as well as Grade 10 extraversion, openness, and neuroticism. The
      individual P items explained unique variance over and above that explained by A
      and C. It was concluded that P is not merely the opposite of A and C.
      Implications for interventions are raised. 

PMID- 24094280
TI  - Children's use of addition to solve two-digit subtraction problems.
AB  - Subtraction problems of the type M - S = ? can be solved with various mental
      calculation strategies. We investigated fourth- to sixth-graders' use of the
      subtraction by addition strategy, first by fitting regression models to the
      reaction times of 32 two-digit subtractions. These models represented three
      different strategy use patterns: the use of direct subtraction, subtraction by
      addition, and switching between the two strategies based on the magnitude of the
      subtrahend. Additionally, we compared performance on problems presented in two
      presentation formats, i.e., a subtraction format (81 - 37 = .) and an addition
      format (37 + . = 81). Both methods converged to the conclusion that children of
      all three grades switched between direct subtraction and subtraction by addition
      based on the combination of two features of the subtrahend: If the subtrahend was
      smaller than the difference, direct subtraction was the dominant strategy; if the
      subtrahend was larger than the difference, subtraction by addition was mainly
      used. However, this performance pattern was only observed when the numerical
      distance between subtrahend and difference was large. These findings indicate
      that theoretical models of children's strategy choices in subtraction should
      include the nature of the subtrahend as an important factor in strategy
      selection. 

PMID- 24094281
TI  - Vitalistic thinking in adults.
AB  - Vitalistic thinking has traditionally been associated with reasoning about
      biological phenomena. The current research aimed to investigate a broader range
      of vitalistic thinking than previously studied. Esoteric notions of 'energy' are
      frequently used by individuals when making causal attributions for strange
      occurrences, and previous literature has linked such thinking with paranormal,
      magical, and superstitious beliefs. Two experiments are described that aim to
      investigate whether adults are vitalistic when asked to make causal judgments,
      and whether this can be predicted by thinking styles and prior paranormal belief.
      Experiment 1 asked participants to rate three causal options (one of which was
      vitalistic) for six vignettes. Scores on one dimension of paranormal belief (New
      Age Philosophy) and analytical thinking significantly predicted vitalism, but
      scores on intuitive thinking and Traditional Paranormal Beliefs did not.
      Experiment 2 extended the findings by asking participants to generate their own
      causal responses. Again, paranormal belief was found to be the best predictor of
      vitalism, but this time Traditional Paranormal Beliefs were associated with
      vitalistic responses whilst both intuitive and analytical thinking were unable to
      significantly predict classification. Results challenge previous findings,
      suggesting that vitalistic thinking may operate differently when applied to
      everyday causal reasoning. 

PMID- 24094283
TI  - We'll never get past the glass ceiling! Meta-stereotyping, world-views and
      perceived relative group-worth.
AB  - This article examines the implications of perceived negativity from members of a
      dominant outgroup on the world views and perceived relative group worth of
      members of disadvantaged groups. We hypothesized that concerns about the negative
      opinions a dominant outgroup is perceived to hold of the ingroup (i.e., meta
      stereotypes) would undermine group members' views about societal fairness. We
      expected this trend to be mediated by recall of previous personal experiences of
      discrimination. We further hypothesized that members' views about societal
      fairness would predict their perception of the ingroup's worth relative to the
      outgroup - such that undermined views about societal fairness would be associated
      with lower perceived ingroup worth relative to the outgroup. Taken jointly,
      results from two studies using two real intergroup contexts support these
      hypotheses and are discussed in terms of their implications for the social
      mobility of members of disadvantaged groups. 

PMID- 24094282
TI  - Anxiety and chronic couple relationship stress moderate adrenocortical response
      to couple interaction in expectant parents.
AB  - The study examines whether anxiety or chronic relationship stress alter the way
      that couple conflict affects cortisol levels for women and men during the
      transition to parenthood. Saliva samples, assayed for cortisol, were collected
      before and after couple interaction from 128 heterosexual couples expecting their
      first child. Confirming prior research, expectant mothers had higher cortisol
      levels than their spouses, and gestational age was linked to women's cortisol
      level. Negativity during couple interaction was associated with greater cortisol
      reactivity for men, but not women. Tests of moderation indicated little relation
      between negativity and cortisol recovery for individuals with a low level of
      anxiety or little history of chronic arguing with the partner. However, among
      individuals with elevated levels of either of these two factors, negativity was
      linked to less cortisol recovery for men, but more cortisol recovery for women.
      Consistent results were also found for the relation between low warmth in the
      couple interaction and both reactivity and recovery for men and women high in
      anxiety. Future research should examine whether pregnancy is responsible for
      these different gender patterns, or whether the inhibition of negativity is
      stressful for women with high levels of risk. 

PMID- 24094284
TI  - The telltale face: possible mechanisms behind defector and cooperator recognition
      revealed by emotional facial expression metrics.
AB  - In this study, we investigated the role of facial cues in cooperator and defector
      recognition. First, a face image database was constructed from pairs of full face
      portraits of target subjects taken at the moment of decision-making in a
      prisoner's dilemma game (PDG) and in a preceding neutral task. Image pairs with
      no deficiencies (n = 67) were standardized for orientation and luminance. Then,
      confidence in defector and cooperator recognition was tested with image rating in
      a different group of lay judges (n = 62). Results indicate that (1) defectors
      were better recognized (58% vs. 47%), (2) they looked different from cooperators
      (p < .01), (3) males but not females evaluated the images with a relative bias
      towards the cooperator category (p < .01), and (4) females were more confident in
      detecting defectors (p < .05). According to facial microexpression analysis,
      defection was strongly linked with depressed lower lips and less opened eyes.
      Significant correlation was found between the intensity of micromimics and the
      rating of images in the cooperator-defector dimension. In summary, facial
      expressions can be considered as reliable indicators of momentary social
      dispositions in the PDG. Females may exhibit an evolutionary-based overestimation
      bias to detecting social visual cues of the defector face. 

PMID- 24094285
TI  - Sexually dimorphic preference for altruism in the opposite sex according to
      recipient.
AB  - Sexual selection may affect human altruistic behaviour. Evolutionary psychology
      predicts that human mate preference reflects sexual selection. We investigated
      sex differences in preference for opposite-sex altruism according to recipient
      because the reasons for altruistic behaviour differ according to the relationship
      between actor and recipient. We employed the Self-Report Altruism Scale
      Distinguished by the Recipient, which was newly developed to evaluate altruism
      among Japanese undergraduates. We asked participants to evaluate preferences for
      each item based on the recipient of the altruistic behaviour (family members,
      friends or acquaintances, and strangers). Preference for opposite-sex altruism
      differed according to recipient, gender of the participant, and relationship
      type, and several significant interactions were observed among these factors. We
      suggest that whereas women use a potential partner's altruism towards strangers
      as a costly signal of their resource-holding potential when choosing a mate, they
      consider altruism towards family when they are in a long-term relationship to
      ensure that resources are not allocated to non-relatives. 

PMID- 24094286
TI  - Differences in the prognostic implications of vascular invasion between lung
      adenocarcinoma and squamous cell carcinoma.
AB  - OBJECTIVES: Vascular invasion (VI) has been accepted as a universally important
      prognostic factor for patients with lung carcinoma. However, the clinical
      significance of VI in each of the histological subtypes has been unclear. The aim
      of the present study was to investigate differences in the clinicopathological
      implications of VI between adenocarcinoma and squamous cell carcinoma. METHOD: A
      total of 336 patients were evaluated, of whom 81 were diagnosed as having
      peripheral-type squamous cell carcinoma, and 255 as having adenocarcinoma.
      RESULT: Among the 336 patients, the five-year survival rates for those who were
      VI-positive and VI-negative were 38.4% and 76.3%, respectively, the difference
      being significant (p<0.0001). Multivariate analysis identified VI as an
      independent prognostic factor (hazard ratio: 1.86). Although the difference in
      cancer-free survival between VI-positive and -negative patients was statistically
      significant for adenocarcinoma (p<0.0001), it was not significant for squamous
      cell carcinoma (p=0.086). For adenocarcinoma, the difference between the survival
      curves for VI-positive and -negative patients was significant for the subtypes
      with a predominant lepidic (p<0.0001), papillary (p=0.0026), and acinar
      (p=0.0060) component, whereas that for the predominantly solid subtype was not
      significant (p=0.58). Squamous cell carcinomas were then divided into two groups
      on the basis of the diameter of vessels that had been invaded by the cancer
      cells: large-vessel invasion (LVI; 1000 MUm or more) and small-vessel invasion
      (SVI; less than 1000 MUm). Although there was no difference in the survival
      curves between the LVI and SVI groups, the LVI group showed a significantly
      higher incidence of cavity formation and distant metastasis. CONCLUSION: We
      conclude that VI is a useful prognostic indicator in lung carcinoma, although the
      clinical implications of VI differ between adenocarcinoma and squamous cell
      carcinoma.

PMID- 24094287
TI  - Strategies for improving outcomes in NSCLC: a look to the future.
AB  - Advances in the management of non-small cell lung cancer (NSCLC) over the past 30
      years have led to small increases in 5-year survival rates across Europe, though
      further improvements may require new treatment strategies. In order to improve
      efficiency and reduce the cost of development, future trials for new targeted
      agents in NSCLC should aim to recruit patients on the basis of tumour biology
      rather than clinical characteristics. However, identification of predictive
      biomarkers is required to maximise the benefits of new approaches and expedite
      the drug development process. Nevertheless, the NSCLC landscape is changing
      rapidly, and recent improvements in our understanding of the molecular biology of
      the disease will help in the identification of novel targeted agents as well as
      assisting in the development of personalised strategies for the numerous small
      subsets of defined NSCLC. Progress in imaging and treatment delivery is also
      likely to improve outcomes for patients with the disease. This article outlines
      recent progress in the treatment of NSCLC, identifies current challenges and
      describes proposals for improving the future management of the disease. It is
      hoped that implementation of some of these strategies will go some way to
      improving the outlook for patients with NSCLC. 

PMID- 24094289
TI  - Renal responses to acute volume expansion in spontaneously hypertensive rats is
      related to the baseline sodium excretion.
AB  - Essential hypertension is associated with an exaggerated natriuresis in response
      to intravenous infusion of isotonic saline. We examined proximal tubular fluid
      output and segmental tubular handling of sodium in conscious spontaneously
      hypertensive rats (SHR), their normotensive counterparts Wistar-Kyoto rats (WKY),
      and ordinary Wistar rats using servo-controlled sodium and fluid balance and Li
      clearance technique. Sodium (Na) excretion rose to 2.72 +/- 0.75 (by a factor of
      8) and 1.73 +/- 0.68 MUmol/min (by a factor of 6.3) (p < 0.05) in SHR and WKY,
      respectively, thus confirming the presence of exaggerated natriuresis in SHR.
      FE(Li) rose to 34 +/- 4 and 29 +/- 2 (p < 0.05) and C(Na)/C(Li) rose to 3.0 +/-
      0.8 and 2.0 +/- 0.6 (p < 0.05) in SHR and WKY, respectively, demonstrating that
      Na reabsorption in both the proximal and the distal nephron was involved.
      Additional experiments showed that giving the rats saline instead of water to
      drink for four days prior to the clearance measurement led to a remarkable
      increase in the natriuretic response to volume expansion. There was a close
      correlation between the peak increase in FE(Na) and the logarithmic values of the
      baseline FE(Na) values. In conclusion, the study confirms the presence of an
      exaggerated natriuresis in response to volume expansion in conscious SHR rats
      compared to WKY rats, and that the renal response to acute volume expansion is
      related to the baseline sodium excretion.

PMID- 24094288
TI  - Using a mobility assistance dog reduces upper limb effort during manual
      wheelchair ramp ascent in an individual with spinal cord injury.
AB  - OBJECTIVE: To compare the mechanical and muscular efforts generated in the non
      dominant upper limb (U/L) when ascending a ramp with and without the use of a
      mobility assistance dog (AD(Mob)) in a manual wheelchair user with a spinal cord
      injury. METHOD: The participant ascended a ramp at natural speed using his
      personal wheelchair with (three trials) and without (three trials) his AD(Mob).
      Movement parameters of the wheelchair, head, trunk, and non-dominant U/L (i.e.
      hand, forearm, and arm segments) were recorded with a motion analysis system. The
      orthogonal force components applied on the hand rims by the U/Ls were computed
      with instrumented wheels. Muscular activity data of the clavicular fibers of the
      pectoralis major, the anterior fibers of the deltoid, the long head of the biceps
      brachii, and the long head of the triceps brachii were collected at the non
      dominant U/L. RESULTS: During uphill propulsion with the AD(Mob), the total and
      tangential forces applied at the non-dominant handrim, along with the rate of
      rise of force, were reduced while mechanical efficiency was improved compared to
      uphill propulsion without the AD(Mob). Similarly, the resultant net joint
      movements (wrist, elbow, and shoulder) and the relative muscular demands (biceps,
      triceps, anterior deltoid, pectoralis major) decreased during uphill propulsion
      with an AD(Mob) versus without an AD(Mob). CONCLUSION: Propelling uphill with the
      assistance of an AD(Mob) reduces U/L efforts and improves efficiency compared to
      propelling uphill without its assistance in a manual wheelchair user with a
      spinal cord injury.

PMID- 24094290
TI  - Serum creatinine is associated with coronary disease risk even in the absence of
      metabolic disorders.
AB  - BACKGROUND: In view of recent evidence that serum creatinine and dysfunctional
      apolipoprotein (apo)A-I may serve as inflammation mediators in people with
      enhanced inflammation, we studied whether or not these molecules were
      interrelated and associated with coronary heart disease (CHD) likelihood even in
      subjects without metabolic syndrome (MetS) or type-2 diabetes. METHODS: Among
      unselected middle-aged Turkish adults with available serum apo A-I,
      lipoprotein(a) and creatinine measurements, 697 participants (designated as
      'healthy') were enrolled, after exclusion of the stated metabolic disorders. CHD
      was identified in 87 subjects, roughly half during 3.1 years' follow-up. RESULTS:
      'Healthy' individuals were overweight and had partly impaired fasting glucose but
      otherwise normal serum creatinine and other biochemical measurements. Being
      consistent with lacking anti-inflammatory activity, apoA-I was linearly and
      positively associated with apoB, in women further with creatinine. Logistic
      regression analyses showed that, beyond age, not non-HDL-cholesterol, systolic
      blood pressure and smoking status, but serum creatinine in each sex (OR in men
      1.63 [95% CI 1.14; 2.31]) and CRP in women were significantly associated with CHD
      likelihood. The combined highest and lowest creatinine quartiles in women
      displayed an OR 2.14 (1.02; 4.51) compared with the intermediate quartiles, after
      similar adjustments. CONCLUSION: Elevated creatinine levels within normal range,
      linked to apoA-I dysfunctionality, are independently associated with CHD
      likelihood even in non-diabetic subjects without MetS. In such women the lowest
      creatinine quartile is also linked to CHD risk.

PMID- 24094291
TI  - Inclusion of glycerol in forage diets increases methane production in a rumen
      simulation technique system.
AB  - We hypothesised that the inclusion of glycerol in the forage diets of ruminants
      would increase the proportion of propionate produced and thereby decrease in
      vitro CH4 production. This hypothesis was examined in the present study using a
      semi-continuous fermentation system (rumen simulation technique) fed a brome hay
      (8.5 g) and maize silage (1.5 g) diet with increasing concentrations (0, 50, 100
      and 150 g/kg DM) of glycerol substituted for maize silage. Glycerol linearly
      increased total volatile fatty acids production (P<0.001). Acetate production was
      quadratically affected (P=0.023) and propionate and butyrate production was
      linearly increased (P<0.001). Glycerol linearly increased (P=0.011) DM
      disappearance from hay and silage. Crude protein disappearance from hay was not
      affected (P=0.789), but that from silage was linearly increased (P<0.001) with
      increasing glycerol concentrations. Neutral-detergent fibre (P=0.040) and acid
      detergent fibre (P=0.031) disappearance from hay and silage was linearly
      increased by glycerol. Total gas production tended to increase linearly (P=0.061)
      and CH4 concentration in gas was linearly increased (P<0.001) by glycerol,
      resulting in a linear increase (P<0.001) in mg CH4/g DM digested. Our hypothesis
      was rejected as increasing concentrations of glycerol in a forage diet linearly
      increased CH4 production in semi-continuous fermenters, despite the increases in
      the concentrations of propionate. In conclusion, this apparent discrepancy is due
      to the more reduced state of glycerol when compared with carbohydrates, which
      implies that there is no net incorporation of electrons when glycerol is
      metabolised to propionate.

PMID- 24094293
TI  - Estimating water consumption of potential natural vegetation on global dry lands:
      building an LCA framework for green water flows.
AB  - This study aimed to provide a framework for assessing direct soil-water
      consumption, also termed green water in the literature, in life cycle assessment
      (LCA). This was an issue that LCA had not tackled before. The approach, which is
      applied during the life cycle inventory phase (LCI), consists of quantifying the
      net change in the evapo(transpi)ration of the production system compared to the
      natural reference situation. Potential natural vegetation (PNV) is used as the
      natural reference situation. In order to apply the method, we estimated PNV
      evapotranspiration adapted to local biogeographic conditions, on global dry
      lands, where soil-water consumption impacts can be critical. Values are reported
      at different spatial aggregation levels: 10-arcmin global grid, ecoregions (501
      units), biomes (14 units), countries (124 units), continents, and a global
      average, to facilitate the assessment for different spatial information detail
      levels available in the LCI. The method is intended to be used in rain-fed
      agriculture and rainwater harvesting contexts, which includes direct soil
      moisture uptake by plants and rainwater harvested and then reused in production
      systems. The paper provides the necessary LCI method and data for further
      development of impact assessment models and characterization factors to evaluate
      the environmental effects of the net change in evapo(transpi)ration. 

PMID- 24094292
TI  - DNMT1 and AIM1 Imprinting in human placenta revealed through a genome-wide screen
      for allele-specific DNA methylation.
AB  - BACKGROUND: Genomic imprinting is an epigenetically regulated process wherein
      genes are expressed in a parent-of-origin specific manner. Many imprinted genes
      were initially identified in mice; some of these were subsequently shown not to
      be imprinted in humans. Such discrepancy reflects developmental, morphological
      and physiological differences between mouse and human tissues. This is
      particularly relevant for the placenta. Study of genomic imprinting thus needs to
      be carried out in a species and developmental stage-specific manner. We describe
      here a new strategy to study allele-specific DNA methylation in the human
      placenta for the discovery of novel imprinted genes. RESULTS: Using this
      methodology, we confirmed 16 differentially methylated regions (DMRs) associated
      with known imprinted genes. We chose 28 genomic regions for further testing and
      identified two imprinted genes (DNMT1 and AIM1). Both genes showed maternal
      allele-specific methylation and paternal allele-specific transcription. Imprinted
      expression for AIM1 was conserved in the cynomolgus macaque placenta, but not in
      other macaque tissues or in the mouse. CONCLUSIONS: Our study indicates that
      while there are many genomic regions with allele-specific methylation in tissues
      like the placenta, only a small sub-set of them are associated with allele
      specific transcription, suggesting alternative functions for such genomic
      regions. Nonetheless, novel tissue-specific imprinted genes remain to be
      discovered in humans. Their identification may help us better understand
      embryonic and fetal development.

PMID- 24094294
TI  - Normal cognitive aging.
AB  - Even those who do not experience dementia or mild cognitive impairment may
      experience subtle cognitive changes associated with aging. Normal cognitive
      changes can affect an older adult's everyday function and quality of life, and a
      better understanding of this process may help clinicians distinguish normal from
      disease states. This article describes the neurocognitive changes observed in
      normal aging, followed by a description of the structural and functional
      alterations seen in aging brains. Practical implications of normal cognitive
      aging are then discussed, followed by a discussion of what is known about factors
      that may mitigate age-associated cognitive decline. 

PMID- 24094296
TI  - Cognitive and emotional dysfunction in mild cognitive impairment.
AB  - Although mild cognitive impairment (MCI) is a widely accepted construct both
      clinically and in the research literature, it remains a heterogeneous condition
      that varies in presentation and prognosis. This article first reviews the
      evolution of the diagnosis of MCI, followed by examination of pros and cons of
      cognitive assessments commonly used to assess for MCI. Emotional changes commonly
      seen in MCI are also reviewed. Finally, the relation between cognitive and
      emotional dysfunction is examined, including a discussion of specific
      psychological symptoms seen in subtypes of MCI, and how the presence of
      neuropsychiatric symptoms may affect the risk for progression to dementia. 

PMID- 24094295
TI  - Classification and epidemiology of MCI.
AB  - Mild cognitive impairment (MCI) is an intermediate stage in the trajectory from
      normal cognition to dementia. Despite controversies about the classification of
      MCI, recent published criteria for MCI allow better comparison of the prevalence,
      incidence, and outcomes of MCI. Subjects with MCI have a high rate of progression
      to dementia over a relatively short period. In this review, we present an
      overview of the classification of MCI, estimates of the incidence and prevalence
      of MCI, risk factors for MCI, and the outcomes following an MCI diagnosis. 

PMID- 24094297
TI  - Clinical evaluation of early cognitive symptoms.
AB  - The etiology of cognitive impairment in older adults is almost always a clinical
      diagnosis without definitive biomarkers. The clinical evaluation, therefore, is
      indispensable. Evaluating cognitive symptoms requires a deliberate approach to
      define the onset, course, and nature of symptoms. An informant who knows the
      patient well is essential. The physician must have a working knowledge of the
      basics of cognitive function. The neurologic examination also is fundamental to
      defining the origin of cognitive impairment. Extraocular movements, speech, and
      gait are examples of high-yield examination findings that can be observed and
      tested quickly, adding to the clinical impression. 

PMID- 24094299
TI  - Using neuroimaging to inform clinical practice for the diagnosis and treatment of
      mild cognitive impairment.
AB  - Advances in structural and functional neuroimaging techniques have unquestionably
      improved understanding of the development and progression of Alzheimer disease
      (AD), with evidence supporting regional (and network) change that underlies
      cognitive decline across the "healthy" aging/mild cognitive impairment (MCI)/AD
      spectrum. This review focuses on visual rating scales and volumetric analyses
      that could be easily integrated into clinical practice, followed by a review of
      functional neuroimaging findings suggesting that widespread cerebral dysfunction
      underlies the learning and memory deficits in MCI. Evidence of preserved
      neuroplasticity in this population and that cognitive rehabilitation techniques
      may capitalize on this plasticity to improve cognition in those with MCI is also
      discussed. 

PMID- 24094298
TI  - Emerging biomarkers in cognition.
AB  - Knowledge of aging and dementia is rapidly evolving with the aim of identifying
      individuals in the earliest stages of disease processes. Biomarkers allow
      clinicians to show the presence of a pathologic process and resultant synapse
      dysfunction and neurodegeneration, even in the earliest stages. This article
      focuses on biomarkers for mild cognitive impairment caused by Alzheimer disease,
      structural magnetic resonance imaging, fluorodeoxyglucose positron emission
      tomography (PET) or single-photon emission computed tomography, and PET with
      dopamine ligands. Although these biomarkers are useful, several limitations
      exist. Several new biomarkers are emerging and a more biological characterization
      of underlying pathophysiologic spectra may become possible. 

PMID- 24094300
TI  - Current management decisions in mild cognitive impairment.
AB  - Efforts toward early detection of Alzheimer disease (AD) have focused on
      refinement and identification of diagnostic markers, with the goal of preventing
      or delaying disease progression. Mild cognitive impairment (MCI) has emerged as a
      potential precursor to dementia. Though not without controversy, MCI has been
      associated with an increased risk for conversion to AD. In this article, with
      emphasis on meta-analyses, randomized controlled trials, and extant literature
      reviews, considerations and recommendations for optimal clinical management of
      MCI are offered. Given the substantial heterogeneity of this patient population
      and inconsistent research methodologies, the need for informed, clinical judgment
      is critical. 

PMID- 24094302
TI  - Dealing with mild cognitive impairment: help for patients and caregivers.
AB  - Mild cognitive impairment (MCI) is a unique entity in the spectrum of syndromes
      of cognitive loss. Many patients referred for evaluation of memory loss come with
      an assumption that they already have dementia. When patients are diagnosed with
      MCI, they and their caregivers have to deal with the challenge of uncertainties.
      Patient and family education must stress the uncertainty of whether the deficits
      will progress. This article aims to guide the clinician who has reached a
      diagnosis of MCI and is working with the patient and family on coping with the
      uncertainties of MCI. 

PMID- 24094303
TI  - Mild Cognitive Impairment. Preface.

PMID- 24094301
TI  - Risk factors for the progression of mild cognitive impairment to dementia.
AB  - The increasing prevalence of cognitive impairment among the older adult
      population warrants attention to the identification of practices that may
      minimize the progression of early forms of cognitive impairment, including the
      transitional stage of mild cognitive impairment (MCI), to permanent stages of
      dementia. This article identifies both markers of disease progress and risk
      factors linked to the progression of MCI to dementia. Potentially modifiable risk
      factors may offer researchers a point of intervention to modify the effect of the
      risk factor and to minimize the future burden of dementia. 

PMID- 24094304
TI  - Association of folic acid receptor alpha in maternal serum with neural tube
      defects.
AB  - OBJECTIVE: To evaluate whether serum folic receptor alpha levels are changed in
      women whose previous pregnancies were complicated with neural tube defects
      (NTDs). METHODS: This was a case-control study that included 41 women as the
      control group who had previously had at least one healthy pregnancy and 37 women
      as the study group who had a previous pregnancy complicated with NTDs. Blood
      samples were obtained from all of the participants six weeks after the
      termination of pregnancy or delivery of a baby. Serum folate receptor alpha
      concentrations were analyzed using a commercially available enzyme-linked
      immunosorbent assay (ELISA) kit. RESULTS: The mean concentrations of serum folate
      receptor alpha were significantly lower in the NTD cases compared to those in the
      control group (p = 0.02). There was no significant difference in mean serum
      folate titers between the NTD cases and the control group (p = 0.07). CONCLUSION:
      Low serum folic acid receptor alpha levels in the current study did not appear to
      be a regulatory marker of maternal folate homeostasis per se but rather a factor
      that contributed to the development of NTDs.

PMID- 24094305
TI  - Shotgun label-free quantitative proteomics of water-deficit-stressed midmature
      peanut (Arachis hypogaea L.) seed.
AB  - Legume seeds and peanuts, in particular, are an inexpensive source of plant
      proteins and edible oil. A comprehensive understanding of seed metabolism and the
      effects of water-deficit stress on the incorporation of the main storage reserves
      in seeds, such as proteins, fatty acids, starch, and secondary metabolites, will
      enhance our ability to improve seed quality and yield through molecular breeding
      programs. In the present study, we employed a label-free quantitative proteomics
      approach to study the functional proteins altered in the midmature (65-70 days
      postanthesis) peanut seed grown under water-deficit stress conditions. We created
      a pod-specific proteome database and identified 93 nonredundant, statistically
      significant, and differentially expressed proteins between well-watered and
      drought-stressed seeds. Mapping of these differential proteins revealed three
      candidate biological pathways (glycolysis, sucrose and starch metabolism, and
      fatty acid metabolism) that were significantly altered due to water-deficit
      stress. Differential accumulation of proteins from these pathways provides
      insight into the molecular mechanisms underlying the observed physiological
      changes, which include reductions in pod yield and biomass, reduced germination,
      reduced vigor, decreased seed membrane integrity, increase in storage proteins,
      and decreased total fatty acid content. Some of the proteins encoding rate
      limiting enzymes of biosynthetic pathways could be utilized by breeders to
      improve peanut seed production during water-deficit conditions in the field. The
      data have been deposited to the ProteomeXchange with identifier PXD000308. 

PMID- 24094307
TI  - Laser cataract surgery: curse of the small pupil.

PMID- 24094308
TI  - Clinical and ultrasound biomicroscopic findings in a patient with anterior
      vaulting of a customized, flexible artificial iris.

PMID- 24094309
TI  - Pentacam HR criteria for curvature change in keratoconus and postoperative LASIK
      ectasia.

PMID- 24094310
TI  - Intra-eye visual function comparison with and without a central hole contact lens
      based system: potential applications to ICL design.
AB  - PURPOSE: To evaluate the effects of a central hole contact lens-based design on
      visual performance and to compare it with the standard version of that same
      contact lens without the hole (non-hole scenario). METHODS: The visual
      performance of 10 myopic patients wearing either a central hole myopic contact
      lens or its corresponding standard version (non-hole contact lens) was assessed
      on the same eye. Monocular corrected distance visual acuity was measured under
      photopic conditions and monocular contrast sensitivity was measured under both
      photopic and mesopic conditions and higher-order ocular aberrations using
      Hartmann-Shack aberrometry. An in vitro optical analysis of both contact lenses
      was performed and a symptoms questionnaire was administered to the participants.
      RESULTS: No statistically significant differences in terms of corrected distance
      visual acuity were found: -0.091 and -0.098 logMAR for the hole and non-hole
      contact lenses, respectively (P > .05). Contrast sensitivity was comparable
      between lenses and no differences were found for specific spatial frequencies or
      a particular luminance level (P > .05). The hole contact lenses provided
      excellent outcomes, essentially equivalent to those of non-hole contact lenses,
      even in terms of subjective symptoms such as glare or halo. In vivo and in vitro
      optical quality analysis revealed no statistically significant differences
      between the hole and the non-hole contact lenses for either pupil size (P > .1).
      CONCLUSION: A contact lens having a central hole provides good visual and optical
      quality outcomes comparable to those yielded by the same lens without a hole. The
      results suggest that the impact of a central hole may be clinically negligible.

PMID- 24094311
TI  - Repeatability of Ocular Response Analyzer waveform parameters in normal eyes and
      eyes after refractive surgery.
AB  - PURPOSE: To study the repeatability of the biomechanical waveform parameters
      measured with the Ocular Response Analyzer (Reichert Ophthalmic Instruments,
      Depew, NY) device in normal eyes and eyes after refractive surgery. METHODS: This
      was a prospective, comparative non-interventional study of a case series. Two
      hundred eyes of 100 patients were divided into five groups: normal eyes of
      patients younger than 30 years, normal eyes of patients between 30 and 50 years
      old, normal eyes of patients older than 50 years, eyes of patients with a history
      of LASIK, and eyes of patients with a history of photorefractive keratectomy. The
      repeatability of the 37 waveform parameters in addition to corneal hysteresis
      (CH), corneal resistance factor (CRF), IOP measurement with Goldmann applanation
      tonometer (IOPg), and IOP evaluated with the intraclass correlation coefficient
      (ICC) (IOPcc) were examined. RESULTS: In addition to IOPg, IOPcc, CRF, and CH,
      five parameters had an ICC greater than 0.6 (substantial agreement): P1area, the
      area of peak 1 (ICC = 0.823); P2area, the area of peak 2 (ICC = 0.646); h1, the
      height of peak 1 (ICC= 0.702); P1area1, the area of peak 1 derived from the upper
      50% of the applanation peak (ICC = 0.772); and h11, the height of peak1 derived
      from the upper 50% of the applanation peak 1 (ICC = 0.697). CONCLUSIONS: This
      study shows that not all parameters derived from the corneal deformation waveform
      signal have the same repeatability. Therefore, analysis of the waveform indices
      should rely on the more repeatable ones to derive consistent conclusions.

PMID- 24094312
TI  - Structural analysis of supramolecular assemblies by hybrid methods.

PMID- 24094313
TI  - Comparison of ReaxFF, DFTB, and DFT for phenolic pyrolysis. 1. Molecular dynamics
      simulations.
AB  - A systematic comparison of atomistic modeling methods including density
      functional theory (DFT), the self-consistent charge density-functional tight
      binding (SCC-DFTB), and ReaxFF is presented for simulating the initial stages of
      phenolic polymer pyrolysis. A phenolic polymer system is simulated for several
      hundred picoseconds within a temperature range of 2500 to 3500 K. The time
      evolution of major pyrolysis products including small-molecule species and char
      is examined. Two temperature zones are observed which demark cross-linking versus
      fragmentation. The dominant chemical products for all methods are similar, but
      the yields for each product differ. At 3500 K, DFTB overestimates CO production
      (300-400%) and underestimates free H (~30%) and small C(m)H(n)O molecules (~70%)
      compared with DFT. At 3500 K, ReaxFF underestimates free H (~60%) and fused
      carbon rings (~70%) relative to DFT. Heterocyclic oxygen-containing five- and six
      membered carbon rings are observed at 2500 K. Formation mechanisms for H2O, CO,
      and char are discussed. Additional calculations using a semiclassical method for
      incorporating quantum nuclear energies of molecules were also performed. These
      results suggest that chemical equilibrium can be affected by quantum nuclear
      effects at temperatures of 2500 K and below. Pyrolysis reaction mechanisms and
      energetics are examined in detail in a companion manuscript.

PMID- 24094314
TI  - Primed to perish: heightened mitochondrial priming explains hESC apoptosis
      sensitivity.
AB  - Human embryonic stem cells (hESCs) are hypersensitive to apoptotic stimuli,
      though the underlying mechanisms are poorly characterized. In this issue of Cell
      Stem Cell, Liu et al. (2013) report that mitochondria of human ESCs exist in an
      apoptosis-prone state, ready to act as cellular executioners upon detecting DNA
      damage. 

PMID- 24094315
TI  - A foot in the door: how the chromatin modifier Brg1 and Pax6 jointly potentiate
      adult neurogenesis.
AB  - Transcription factors and chromatin modifiers are known to contribute to cell
      specification. However, whether and how they jointly act is poorly understood. In
      this issue of Cell Stem Cell, Ninkovic et al. show that Pax6 and Brg1 cooperate
      to modulate gene expression in order to direct neurogenic fate in the olfactory
      bulb. 

PMID- 24094316
TI  - Regional specificity in the Drosophila midgut: setting boundaries with stem
      cells.
AB  - Many organs consist of distinct subregions with specialized physiological roles,
      but how regional boundaries are upheld during cellular renewal is largely
      unknown. Recently, Buchon et al. (2013) and Marianes and Spradling (2013) showed
      that subregions of the Drosophila midgut are maintained by patterned
      transcription factors and compartmentalized stem cell progeny. 

PMID- 24094317
TI  - Build-a-brain.
AB  - A major barrier in understanding nervous system development is modeling the
      cellular interactions that form the human brain. Recently, in the journal Nature,
      Lancaster et al. (2013) established a protocol for culturing pluripotent stem
      cell (PSC)-derived "cerebral organoids" that mimics the developing human brain's
      cellular organization, segregates into distinct brain regions, and models
      microcephaly. 

PMID- 24094318
TI  - Removing reprogramming roadblocks: Mbd3 depletion allows deterministic iPSC
      generation.
AB  - Transcription factor-induced pluripotency is extremely inefficient and assumed to
      be stochastic. In a recent Nature publication, Rais et al. show that depletion of
      the methyl-binding protein 3 yields reprogramming efficiencies of up to 100%
      within days, suggesting that elimination of a single gene suffices to render
      reprogramming a deterministic process. 

PMID- 24094319
TI  - Toward the development of a global induced pluripotent stem cell library.
AB  - The ability to preselect the donor genotype of iPSC lines provides important
      opportunities for immune matching in cell therapy. Here we propose that an
      international assessment should be made of how immune incompatibility can best be
      managed and how a network of GMP HLA homozygous haplobanks could be operated. 

PMID- 24094320
TI  - Banking human induced pluripotent stem cells: lessons learned from embryonic stem
      cells?
AB  - The generation of human embryonic stem cell banking networks has ensured that
      well-characterized and quality controlled stem cell lines are broadly accessible
      to researchers worldwide. Here, we provide recommendations for engaging these
      established networks in efforts to build similar resources for the distribution
      and collection of induced pluripotent stem cells. 

PMID- 24094321
TI  - iPSC crowdsourcing: a model for obtaining large panels of stem cell lines for
      screening.
AB  - A key to tapping the potential of iPSCs is the establishment of readily
      accessible well-characterized panels of lines for custom screening. Here, we
      propose a crowdsourcing strategy to rapidly develop a large repository of iPSCs
      and provide a model for how the NIH could support this effort. 

PMID- 24094322
TI  - Mesenchymal stromal cells: sensors and switchers of inflammation.
AB  - In addition to their stem/progenitor properties, mesenchymal stromal cells (MSCs)
      possess broad immunoregulatory properties that are being investigated for
      potential clinical application in treating immune-based disorders. An informed
      view of the scope of this clinical potential will require a clear understanding
      of the dynamic interplay between MSCs and the innate and adaptive immune systems.
      In this Review, we outline current insights into the ways in which MSCs sense and
      control inflammation, highlighting the central role of macrophage polarization.
      We also draw attention to functional differences seen between vivo and in vitro
      contexts and between species. Finally, we discuss progress toward clinical
      application of MSCs, focusing on GvHD as a case study. 

PMID- 24094323
TI  - Mobilized adult pituitary stem cells contribute to endocrine regeneration in
      response to physiological demand.
AB  - Pituitary hormone deficiencies, with Growth Hormone deficiency being most
      frequent (1 in 3,500-10,000 births), cause significant morbidity. Regeneration of
      missing endocrine cells would be a significant improvement over hormone
      replacement therapies, which incur side effects and do not mimic physiological
      secretion patterns. Recent in vitro studies have identified a population of adult
      pituitary progenitors that express the HMG box transcription factors SOX2 and
      SOX9. Here, we apply cell-lineage tracing analysis to demonstrate that SOX2- and
      SOX9-expressing progenitors can self-renew and give rise to endocrine cells in
      vivo, suggesting that they are tissue stem cells. Moreover, we show that they can
      become mobilized and differentiate into the appropriate endocrine cell types in
      response to physiological stress. Our results highlight the pituitary as a model
      for exploring how physiological changes influence stem cell behavior and suggest
      that manipulation of endogenous pituitary stem cells is a potential therapeutic
      strategy for pituitary deficiencies.

PMID- 24094324
TI  - Sox2(+) stem/progenitor cells in the adult mouse pituitary support organ
      homeostasis and have tumor-inducing potential.
AB  - Sox2(+) adult mouse pituitary cells can self-renew and terminally differentiate
      in vitro, but their physiological role in vivo and possible contribution to
      oncogenesis remain largely unknown. Using genetic lineage tracing, we show here
      that the Sox2(+) cell compartment of both the embryonic and adult pituitary
      contains stem/progenitor cells that are able to differentiate into all hormone
      producing lineages and contribute to organ homeostasis during postnatal life. In
      addition, we show that targeted expression of oncogenic beta-catenin in Sox2(+)
      cells gives rise to pituitary tumors, but, unexpectedly, the tumor mass is not
      derived from the Sox2(+) mutation-sustaining cells, suggesting a paracrine role
      of Sox2(+) cells in pituitary oncogenesis. Our data therefore provide in vivo
      evidence of a role for Sox2(+) stem/progenitor cells in long-term physiological
      maintenance of the adult pituitary, and highlight an unexpected non-cell
      autonomous role for these cells in the induction of pituitary tumors.

PMID- 24094325
TI  - Global transcriptional and translational repression in human-embryonic-stem-cell
      derived Rett syndrome neurons.
AB  - Rett syndrome (RTT) is caused by mutations of MECP2, a methyl CpG binding protein
      thought to act as a global transcriptional repressor. Here we show, using an
      isogenic human embryonic stem cell model of RTT, that MECP2 mutant neurons
      display key molecular and cellular features of this disorder. Unbiased global
      gene expression analyses demonstrate that MECP2 functions as a global activator
      in neurons but not in neural precursors. Decreased transcription in neurons was
      coupled with a significant reduction in nascent protein synthesis and lack of
      MECP2 was manifested as a severe defect in the activity of the AKT/mTOR pathway.
      Lack of MECP2 also leads to impaired mitochondrial function in mutant neurons.
      Activation of AKT/mTOR signaling by exogenous growth factors or by depletion of
      PTEN boosted protein synthesis and ameliorated disease phenotypes in mutant
      neurons. Our findings indicate a vital function for MECP2 in maintaining active
      gene transcription in human neuronal cells. 

PMID- 24094326
TI  - Induction of multipotential hematopoietic progenitors from human pluripotent stem
      cells via respecification of lineage-restricted precursors.
AB  - Human pluripotent stem cells (hPSCs) represent a promising source of patient
      specific cells for disease modeling, drug screens, and cellular therapies.
      However, the inability to derive engraftable human hematopoietic stem and
      progenitor cells (HSPCs) has limited their characterization to in vitro assays.
      We report a strategy to respecify lineage-restricted CD34(+)CD45(+) myeloid
      precursors derived from hPSCs into multilineage progenitors that can be expanded
      in vitro and engrafted in vivo. HOXA9, ERG, and RORA conferred self-renewal and
      multilineage potential in vitro and maintained primitive CD34(+)CD38(-) cells.
      Screening cells via transplantation revealed that two additional factors, SOX4
      and MYB, conferred engraftment. Progenitors specified with all five factors gave
      rise to reproducible short-term engraftment with myeloid and erythroid lineages.
      Erythroid precursors underwent hemoglobin switching in vivo, silencing embryonic
      and activating adult globin expression. Our combinatorial screening approach
      establishes a strategy for obtaining transcription-factor-mediated engraftment of
      blood progenitors from human pluripotent cells. 

PMID- 24094330
TI  - Evaluating and improving neonatal transport services.
AB  - Interfacility transport is a necessary part of hospital care. Neonates often need
      to access specialist input at different sites necessitating a reliable transfer
      process. Services have evolved significantly over the last ten years to meet this
      need. This followed the recognition that ad hoc arrangements were unreliable and
      often unsafe. Services have significantly improved during this time. Attention
      has been paid to training, clinical governance, disseminating best practice,
      setting standards, ring fenced funding and supporting parents. Transport teams
      have become integral to neonatal network function and quality and performance of
      transport services needs to be evaluated. National audit creates useful team
      comparisons and identifies outlier status allowing closer inspection of
      variations between services. Work is needed in the form of external appraisal in
      order to maintain service standards. 

PMID- 24094331
TI  - Computational approaches to species phylogeny inference and gene tree
      reconciliation.
AB  - An intricate relation exists between gene trees and species phylogenies, due to
      evolutionary processes that act on the genes within and across the branches of
      the species phylogeny. From an analytical perspective, gene trees serve as
      character states for inferring accurate species phylogenies, and species
      phylogenies serve as a backdrop against which gene trees are contrasted for
      elucidating evolutionary processes and parameters. In a 1997 paper, Maddison
      discussed this relation, reviewed the signatures left by three major evolutionary
      processes on the gene trees, and surveyed parsimony and likelihood criteria for
      utilizing these signatures to elucidate computationally this relation. Here, I
      review progress that has been made in developing computational methods for
      analyses under these two criteria, and survey remaining challenges. 

PMID- 24094332
TI  - Is HIV short-sighted? Insights from a multistrain nested model.
AB  - An important component of pathogen evolution at the population level is evolution
      within hosts. Unless evolution within hosts is very slow compared to the duration
      of infection, the composition of pathogen genotypes within a host is likely to
      change during the course of an infection, thus altering the composition of
      genotypes available for transmission as infection progresses. We develop a nested
      modeling approach that allows us to follow the evolution of pathogens at the
      epidemiological level by explicitly considering within-host evolutionary dynamics
      of multiple competing strains and the timing of transmission. We use the
      framework to investigate the impact of short-sighted within-host evolution on the
      evolution of virulence of human immunodeficiency virus (HIV), and find that the
      topology of the within-host adaptive landscape determines how virulence evolves
      at the epidemiological level. If viral reproduction rates increase significantly
      during the course of infection, the viral population will evolve a high level of
      virulence even though this will reduce the transmission potential of the virus.
      However, if reproduction rates increase more modestly, as data suggest, our model
      predicts that HIV virulence will be only marginally higher than the level that
      maximizes the transmission potential of the virus. 

PMID- 24094333
TI  - Not everything is black and white: color and behavioral variation reveal a
      continuum between cryptic and aposematic strategies in a polymorphic poison frog.
AB  - Aposematism and crypsis are often viewed as two extremes of a continuum of visual
      conspicuousness to predators. Theory predicts that behavioral and coloration
      conspicuousness should vary in tandem along the conspicuousness spectrum for
      antipredator strategies to be effective. Here we used visual modeling of contrast
      and behavioral observations to examine the conspicuousness of four populations of
      the granular poison frog, Oophaga granulifera, which exhibits almost continuous
      variation in dorsal color. The patterns of geographic variation in color, visual
      contrast, and behavior support a gradient of overall conspicuousness along the
      distribution of O. granulifera. Red and green populations, at the extremes of the
      color distribution, differ in all elements of color, contrast, and behavior,
      strongly reflecting aposematic and cryptic strategies. However, there is no
      smooth cline in any elements of behavior or coloration between the two extremes.
      Instead populations of intermediate colors attain intermediate conspicuousness by
      displaying different combinations of aposematic and cryptic traits. We argue that
      coloration divergence among populations may be linked to the evolution of a
      gradient of strategies to balance the costs of detection by predators and the
      benefits of learned aversion. 

PMID- 24094334
TI  - Extinction space--a method for the quantification and classification of changes
      in morphospace across extinction boundaries.
AB  - Three main modes of extinction are responsible for reductions in morphological
      disparity: (1) random (caused by a nonselective extinction event); (2) marginal
      (a symmetric, selective extinction event trimming the margin of morphospace); and
      (3) lateral (an asymmetric, selective extinction event eliminating one side of
      the morphospace). These three types of extinction event can be distinguished from
      one another by comparing changes in three measures of morphospace occupation: (1)
      the sum of range along the main axes; (2) the sum of variance; and (3) the
      position of the centroid. Computer simulations of various extinction events
      demonstrate that the pre-extinction distribution of taxa (random or normal) in
      the morphospace has little influence on the quantification of disparity changes,
      whereas the modes of the extinction events play the major role. Together, the
      three disparity metrics define an "extinction-space" in which different
      extinction events can be directly compared with one another. Application of this
      method to selected extinction events (Frasnian-Famennian, Devonian-Carboniferous,
      and Permian-Triassic) of the Ammonoidea demonstrate the similarity of the
      Devonian events (selective extinctions) but the striking difference from the end
      Permian event (nonselective extinction). These events differ in their mode of
      extinction despite decreases in taxonomic diversity of similar magnitude. 

PMID- 24094336
TI  - Evolution of habitat preference and nutrition mode in a cosmopolitan fungal genus
      with evidence of interkingdom host jumps and major shifts in ecology.
AB  - Host jumps by microbial symbionts are often associated with bursts of species
      diversification driven by the exploitation of new adaptive zones. The objective
      of this study was to infer the evolution of habitat preference (decaying plants,
      soil, living fungi, and living plants), and nutrition mode (saprotrophy and
      mycoparasitism) in the fungal genus Trichoderma to elucidate possible
      interkingdom host jumps and shifts in ecology. Host and ecological role shifts
      were inferred by phylogenetic analyses and ancestral character reconstructions.
      The results support several interkingdom host jumps and also show that the
      preference for a particular habitat was gained or lost multiple times.
      Diversification analysis revealed that mycoparasitism is associated with
      accelerated speciation rates, which then suggests that this trait may be linked
      to the high number of species in Trichoderma. In this study it was also possible
      to infer the cryptic roles that endophytes or soil inhabitants play in their
      hosts by evaluating their closest relatives and determining their most recent
      ancestors. Findings from this study may have implications for understanding
      certain evolutionary processes such as species radiations in some hyperdiverse
      groups of fungi, and for more applied fields such as the discovery and
      development of novel biological control strategies. 

PMID- 24094337
TI  - Understanding promiscuity: when is seeking additional mates better than guarding
      an already found one?
AB  - Paternity protection and the acquisition of multiple mates select for different
      traits. The consensus from theoretical work is that mate-guarding intensifies
      with an increasing male bias in the adult sex ratio (ASR). A male bias can thus
      lead to male monogamy if guarding takes up the entire male time budget. Given
      that either female- or male-biased ASRs are possible, why is promiscuity clearly
      much more common than male monogamy? We address this question with two models,
      differing in whether males can assess temporal cues of female fertility. Our
      results confirm the importance of the ASR: guarding durations increase with
      decreasing female availability and increasing number of male competitors.
      However, several factors prevent the mating system from switching to male
      monogamy as soon as the ASR becomes male biased. Inefficient guarding, incomplete
      last male sperm precedence, any mechanism that allows sperm to fertilize eggs
      after the male's departure, and (in some cases) the unfeasibility of
      precopulatory guarding all help explain cases where promiscuity exists on its own
      or alongside temporally limited mate-guarding. Shortening the window of
      fertilization shifts guarding time budgets from the postcopulatory to the
      precopulatory stage. 

PMID- 24094335
TI  - Recent gene-capture on the UV sex chromosomes of the moss Ceratodon purpureus.
AB  - Sex chromosomes evolve from ordinary autosomes through the expansion and
      subsequent degeneration of a region of suppressed recombination that is inherited
      through one sex. Here we investigate the relative timing of these processes in
      the UV sex chromosomes of the moss Ceratodon purpureus using molecular population
      genetic analyses of eight newly discovered sex-linked loci. In this system,
      recombination is suppressed on both the female-transmitted (U) sex chromosome and
      the male-transmitted (V) chromosome. Genes on both chromosomes therefore should
      show the deleterious effects of suppressed recombination and sex-limited
      transmission, while purifying selection should maintain homologs of genes
      essential for both sexes on both sex chromosomes. Based on analyses of eight sex
      linked loci, we show that the nonrecombining portions of the U and V chromosomes
      expanded in at least two events (~0.6-1.3 MYA and ~2.8-3.5 MYA), after the
      divergence of C. purpureus from its dioecious sister species, Trichodon
      cylindricus and Cheilothela chloropus. Both U- and V-linked copies showed reduced
      nucleotide diversity and limited population structure, compared to autosomal
      loci, suggesting that the sex chromosomes experienced more recent selective
      sweeps that the autosomes. Collectively these results highlight the dynamic
      nature of gene composition and molecular evolution on nonrecombining portions of
      the U and V sex chromosomes.

PMID- 24094338
TI  - The condition dependency of fitness in males and females: the fitness
      consequences of juvenile diet assessed in environments differing in key adult
      resources.
AB  - Variation in environmental or genetic quality leads to phenotypic variation in
      condition, but how much variation in fitness is created by this variation in
      condition? Using Drosophila melanogaster, we manipulated condition via
      alternative larval diets and then tested several key factors predicted to
      influence how much variation in fitness results from differences in condition.
      Specifically, we were interested in whether male and female fitness are affected
      equally by condition and whether the strength of selection on condition depends
      on the abundance of key resources limiting the reproductive output of each sex.
      We measured selection on condition in alternative assay contexts that varied in
      the abundance of adult food (a key resource for females) or in the abundance of
      females (a key resource for males). Overall, selection tended to be stronger on
      males than females. However, selection on males was weakened when the abundance
      of their key resource (females) was elevated. Increasing the abundance of the key
      resource for females (live yeast) elevated their reproductive output as expected
      but did not change the strength of selection in this sex. Instead, this
      manipulation increased selection on males, suggesting that this environmental
      factor indirectly affects selection on males via their interaction with females. 

PMID- 24094339
TI  - Sex-specific inbreeding depression depends on the strength of male-male
      competition.
AB  - Inbreeding depression has become a central theme in evolutionary biology and is
      considered to be a driving force for the evolution of reproductive morphology,
      physiology, behavior, and mating systems. Despite the overwhelming body of
      empirical work on the reproductive consequences of inbreeding, relatively little
      is known on whether inbreeding depresses male and female fitness to the same
      extent. However, sex-specific inbreeding depression has been argued to affect the
      evolution of selfing rates in simultaneous hermaphrodites and provides a powerful
      approach to test whether selection is stronger in males than in females, which is
      predicted to be the consequence of sexual selection. We tested for sex-specific
      inbreeding depression in the simultaneously hermaphroditic freshwater snail Physa
      acuta by comparing the reproductive performance of both sex functions between
      selfed and outcrossed focal individuals under different levels of male-male
      competition. We found that inbreeding impaired both male and female reproductive
      success and that the magnitude of male inbreeding depression exceeded female
      inbreeding depression when the opportunity for sperm competition was highest. Our
      study provides the first evidence for sex-specific inbreeding depression in a
      hermaphroditic animal and highlights the importance of considering the level of
      male-male competition when assessing sex differences in inbreeding depression. 

PMID- 24094340
TI  - Strong inbreeding depression in two Scandinavian populations of the self
      incompatible perennial herb Arabidopsis lyrata.
AB  - Inbreeding depression is a key factor influencing mating system evolution in
      plants, but current understanding of its relationship with selfing rate is
      limited by a sampling bias with few estimates for self-incompatible species. We
      quantified inbreeding depression (delta) over two growing seasons in two
      populations of the self-incompatible perennial herb Arabidopsis lyrata ssp.
      petraea in Scandinavia. Inbreeding depression was strong and of similar magnitude
      in both populations. Inbreeding depression for overall fitness across two seasons
      (the product of number of seeds, offspring viability, and offspring biomass) was
      81% and 78% in the two populations. Chlorophyll deficiency accounted for 81% of
      seedling mortality in the selfing treatment, and was not observed among offspring
      resulting from outcrossing. The strong reduction in both early viability and late
      quantitative traits suggests that inbreeding depression is due to deleterious
      alleles of both large and small effect, and that both populations experience
      strong selection against the loss of self-incompatibility. A review of available
      estimates suggested that inbreeding depression tends to be stronger in self
      incompatible than in self-compatible highly outcrossing species, implying that
      undersampling of self-incompatible taxa may bias estimates of the relationship
      between mating system and inbreeding depression. 

PMID- 24094341
TI  - Immune evasion and the evolution of molecular mimicry in parasites.
AB  - Parasites that are molecular mimics express proteins which resemble host
      proteins. This resemblance facilitates immune evasion because the immune
      molecules with the specificity to react with the parasite also cross-react with
      the host's own proteins, and these lymphocytes are rare. Given this advantage,
      why are not most parasites molecular mimics? Here we explore potential factors
      that can select against molecular mimicry in parasites and thereby limit its
      occurrence. We consider two hypotheses: (1) molecular mimics are more likely to
      induce autoimmunity in their hosts, and hosts with autoimmunity generate fewer
      new infections (the "costly autoimmunity hypothesis"); and (2) molecular mimicry
      compromises protein functioning, lowering the within-host replication rate and
      leading to fewer new infections (the "mimicry trade-off hypothesis"). Our
      analysis shows that although both hypotheses may select against molecular mimicry
      in parasites, unique hallmarks of protein expression identify whether selection
      is due to the costly autoimmunity hypothesis or the mimicry trade-off hypothesis.
      We show that understanding the relevant selective forces is necessary to predict
      how different medical interventions will affect the proportion of hosts that
      experience the different infection types, and that if parasite evolution is
      ignored, interventions aimed at reducing infection-induced autoimmunity may
      ultimately fail. 

PMID- 24094343
TI  - Developmental instability is genetically correlated with phenotypic plasticity,
      constraining heritability, and fitness.
AB  - Although adaptive plasticity would seem always to be favored by selection, it
      occurs less often than expected. This lack of ubiquity suggests that there must
      be trade-offs, costs, or limitations associated with plasticity. Yet, few costs
      have been found. We explore one type of limitation, a correlation between
      plasticity and developmental instability, and use quantitative genetic theory to
      show why one should expect a genetic correlation. We test that hypothesis using
      the Landsberg erecta * Cape Verde Islands recombinant inbred lines (RILs) of
      Arabidopsis thaliana. RILs were grown at four different nitrogen (N) supply
      levels that span the range of N availabilities previously documented in North
      American field populations. We found a significant multivariate relationship
      between the cross-environment trait plasticity and the within-environment, within
      RIL developmental instability across 13 traits. This genetic covariation between
      plasticity and developmental instability has two costs. First, theory predicts
      diminished fitness for highly plastic lines under stabilizing selection, because
      their developmental instability and variance around the optimum phenotype will be
      greater compared to nonplastic genotypes. Second, empirically the most plastic
      traits exhibited heritabilities reduced by 57% on average compared to nonplastic
      traits. This demonstration of potential costs in inclusive fitness and
      heritability provoke a rethinking of the evolutionary role of plasticity. 

PMID- 24094342
TI  - The evolution of hybrid incompatibilities along a phylogeny.
AB  - The Dobzhansky-Muller model of speciation posits that defects in hybrids between
      species are the result of negative epistatic interactions between alleles that
      arose in independent genetic backgrounds. Tests of one important prediction from
      this model, that incompatibilities "snowball," have relied on comparisons of the
      number of incompatibilities between closely related pairs of species separated by
      different divergence times. How incompatibilities accumulate along phylogenies,
      however, remains poorly understood. We extend the Dobzhansky-Muller model to
      multispecies clades to describe the mathematical relationship between tree
      topology and the number of shared incompatibilities among related pairs of
      species. We use these results to develop a statistical test that distinguishes
      between the snowball and alternative incompatibility accumulation models,
      including nonepistatic and multilocus incompatibility models, in a phylogenetic
      context. We further demonstrate that patterns of incompatibility sharing across
      species pairs can be used to estimate the relative frequencies of different types
      of incompatibilities, including derived-derived versus derived-ancestral
      incompatibilities. Our results and statistical methods should motivate
      comparative genetic mapping of hybrid incompatibilities to evaluate competing
      models of speciation. 

PMID- 24094344
TI  - Fluctuating temperature leads to evolution of thermal generalism and
      preadaptation to novel environments.
AB  - Environmental fluctuations can select for generalism, which is also hypothesized
      to increase organisms' ability to invade novel environments. Here, we show that
      across a range of temperatures, opportunistic bacterial pathogen Serratia
      marcescens that evolved in fluctuating temperature (daily variation between 24
      degrees C and 38 degrees C, mean 31 degrees C) outperforms the strains that
      evolved in constant temperature (31 degrees C). The growth advantage was also
      evident in novel environments in the presence of parasitic viruses and predatory
      protozoans, but less clear in the presence of stressful chemicals. Adaptation to
      fluctuating temperature also led to reduced virulence in Drosophila melanogaster
      host, which suggests that generalism can still be costly in terms of reduced
      fitness in other ecological contexts. While supporting the hypothesis that
      evolution of generalism is coupled with tolerance to several novel environments,
      our results also suggest that thermal fluctuations driven by the climate change
      could affect both species' invasiveness and virulence. 

PMID- 24094345
TI  - Successive gain of insulator proteins in arthropod evolution.
AB  - Alteration of regulatory DNA elements or their binding proteins may have drastic
      consequences for morphological evolution. Chromatin insulators are one example of
      such proteins and play a fundamental role in organizing gene expression. While a
      single insulator protein, CTCF (CCCTC-binding factor), is known in vertebrates,
      Drosophila melanogaster utilizes six additional factors. We studied the evolution
      of these proteins and show here that-in contrast to the bilaterian-wide
      distribution of CTCF-all other D. melanogaster insulators are restricted to
      arthropods. The full set is present exclusively in the genus Drosophila whereas
      only two insulators, Su(Hw) and CTCF, existed at the base of the arthropod clade
      and all additional factors have been acquired successively at later stages.
      Secondary loss of factors in some lineages further led to the presence of
      different insulator subsets in arthropods. Thus, the evolution of insulator
      proteins within arthropods is an ongoing and dynamic process that reshapes and
      supplements the ancient CTCF-based system common to bilaterians. Expansion of
      insulator systems may therefore be a general strategy to increase an organism's
      gene regulatory repertoire and its potential for morphological plasticity. 

PMID- 24094347
TI  - Evolutionary reversals of antibiotic resistance in experimental populations of
      Pseudomonas aeruginosa.
AB  - Antibiotic resistance mutations are accompanied by a fitness cost, and two
      mechanisms allow bacteria to adapt to this cost once antibiotic use is halted.
      First, it is possible for resistance to revert; second, it is possible for
      bacteria to adapt to the cost of resistance by compensatory mutations.
      Unfortunately, reversion to antibiotic sensitivity is rare, but the underlying
      factors that prevent reversion remain obscure. Here, we directly study the
      evolutionary dynamics of reversion by experimentally mimicking reversion
      mutations-sensitives-in populations of rifampicin-resistant Pseudomonas
      aeruginosa. We show that, in our populations, most sensitives are lost due to
      genetic drift when they are rare. However, clonal interference from lineages
      carrying compensatory mutations causes a dramatic increase in the time to
      fixation of sensitives that escape genetic drift, and mutations surpassing the
      sensitives' fitness are capable of driving transiently common sensitive lineages
      to extinction. Crucially, we show that the constraints on reversion arising from
      clonal interference are determined by the potential for compensatory adaptation
      of the resistant population. Although the cost of resistance provides the
      incentive for reversion, our study demonstrates that both the cost of resistance
      and the intrinsic evolvability of resistant populations interact to determine the
      rate and likelihood of reversion. 

PMID- 24094346
TI  - Fisher's geometric model of adaptation meets the functional synthesis: data on
      pairwise epistasis for fitness yields insights into the shape and size of
      phenotype space.
AB  - The functional synthesis uses experimental methods from molecular biology,
      biochemistry and structural biology to decompose evolutionarily important
      mutations into their more proximal mechanistic determinants. However these
      methods are technically challenging and expensive. Noting strong formal parallels
      between R.A. Fisher's geometric model of adaptation and a recent model for the
      phenotypic basis of protein evolution, we sought to use the former to make
      inferences into the latter using data on pairwise fitness epistasis between
      mutations. We present an analytic framework for classifying pairs of mutations
      with respect to similarity of underlying mechanism on this basis, and also show
      that these data can yield an estimate of the number of mutationally labile
      phenotypes underlying fitness effects. We use computer simulations to explore the
      robustness of our approach to violations of analytic assumptions and analyze
      several recently published datasets. This work provides a theoretical complement
      to the functional synthesis as well as a novel test of Fisher's geometric model. 

PMID- 24094348
TI  - Origins, evolution, and diversification of cleptoparasitic lineages in long
      tongued bees.
AB  - The evolution of parasitic behavior may catalyze the exploitation of new
      ecological niches yet also binds the fate of a parasite to that of its host. It
      is thus not clear whether evolutionary transitions from free-living organism to
      parasite lead to increased or decreased rates of diversification. We explore the
      evolution of brood parasitism in long-tongued bees and find decreased rates of
      diversification in eight of 10 brood parasitic clades. We propose a pathway for
      the evolution of brood parasitic strategy and find that a strategy in which a
      closed host nest cell is parasitized and the host offspring is killed by the
      adult parasite represents an obligate first step in the appearance of a brood
      parasitic lineage; this ultimately evolves into a strategy in which an open host
      cell is parasitized and the host offspring is killed by a specialized larval
      instar. The transition to parasitizing open nest cells expanded the range of
      potential hosts for brood parasitic bees and played a fundamental role in the
      patterns of diversification seen in brood parasitic clades. We address the
      prevalence of brood parasitic lineages in certain families of bees and examine
      the evolution of brood parasitism in other groups of organisms. 

PMID- 24094349
TI  - More than one way to produce protein diversity: duplication and limited
      alternative splicing of an adhesion molecule gene in basal arthropods.
AB  - Exon duplication and alternative splicing evolved multiple times in metazoa and
      are of overall importance in shaping genomes and allowing organisms to produce
      many fold more proteins than there are genes in the genome. No other example is
      as striking as the one of the Down syndrome cell adhesion molecule (Dscam) of
      insects and crustaceans (pancrustaceans) involved in the nervous system
      differentiation and in the immune system. To elucidate the evolutionary history
      of this extraordinary gene, we investigated Dscam homologs in two basal
      arthropods, the myriapod Strigamia maritima and the chelicerate Ixodes
      scapularis. In both, Dscam diversified extensively by whole gene duplications
      resulting in multigene expansions. Within some of the S. maritima genes, exons
      coding for one of the immunoglobulin domains (Ig7) duplicated and are mutually
      exclusively alternatively spliced. Our results suggest that Dscam diversification
      was selected independently in chelicerates, myriapods, and pancrustaceans and
      that the usage of Dscam diversity by immune cells evolved for the first time in
      basal arthropods. We propose an evolutionary scenario for the appearance of the
      highly variable Dscam gene of pancrustaceans, adding to the understanding of how
      alternative splicing, exon, and gene duplication contribute to create molecular
      diversity associated with potentially new cellular functions. 

PMID- 24094350
TI  - Local adaptation when competition depends on phenotypic similarity.
AB  - Recent work incorporating demographic-genetic interactions indicates the
      importance of population size, gene flow, and selection in influencing local
      adaptation. This work typically assumes that density-dependent survival affects
      individuals equally, but individuals in natural population rarely compete
      equally. Among-individual differences in resource use generate stronger
      competition between more similar phenotypes (frequency-dependent competition) but
      it remains unclear how this additional form of selection changes the interactions
      between population size, gene flow, and local stabilizing selection. Here, we
      integrate migration-selection dynamics with frequency-dependent competition. We
      developed a coupled demographic-quantitative genetic model consisting of two
      patches connected by dispersal and subject to local stabilizing selection and
      competition. Our model shows that frequency-dependent competition slightly
      increases local adaptation, greatly increases genetic variance within patches,
      and reduces the amount that migration depresses population size, despite the
      increased genetic variance load. The effects of frequency-dependence depend on
      the strength of divergent selection, trait heritability, and when mortality
      occurs in the life cycle in relation to migration and reproduction. Essentially,
      frequency-dependent competition reduces the density-dependent interactions
      between migrants and residents, the extent to which depends on how different and
      common immigrants are compared to residents. Our results add new dynamics that
      illustrate how competition can alter the effects of gene flow and divergent
      selection on local adaptation and population carrying capacities. 

PMID- 24094351
TI  - Asymmetric effects of loss and gain of a floral trait on pollinator preference.
AB  - Shifts in pollination syndromes involve coordinated changes in multiple floral
      traits. This raises the question of how plants can cope with rapid changes in
      pollinator availability by the slow process of accumulation of mutations in
      multiple genes. Here we study the transition from bee to hawkmoth pollination in
      the genus Petunia. Interspecific crosses followed by single locus introgressions
      were used to recreate putative intermediate evolutionary stages in the evolution
      of moth pollination. The effect of the loss/gain of petal color was asymmetric:
      it had no influence on the established pollinator but enhanced visitation by the
      new pollinator. Therefore, shifts in pollination syndromes may proceed through
      intermediate stages of reduced specialization and consequently enhanced
      reproductive assurance. The loss of petal color in moth-pollinated Petunia
      involves null mutations in a single regulatory gene, An2. Such simple genetic
      changes may be sufficiently rapid and frequent to ensure survival during
      pollinator failure. 

PMID- 24094352
TI  - Recent ecological selection on regulatory divergence is shaping clinal variation
      in senecio on Mount Etna.
AB  - The hybrid zone on Mount Etna (Sicily) between Senecio aethnensis and Senecio
      chrysanthemifolius (two morphologically and physiologically distinct species) is
      a classic example of an altitudinal cline. Hybridization at intermediate
      altitudes and gradients in phenotypic and life-history traits occur along
      altitudinal transects of the volcano. The cline is considered to be a good
      example of ecological selection with species differences arising by divergent
      selection opposing gene flow. However, the possibility that the cline formed from
      recent secondary contact following an allopatric phase is difficult to exclude.
      We demonstrate a recent split between S. aethnensis and S. chrysanthemifolius (as
      recent as ~32,000 years ago) and sufficient gene flow (2Nm > 1) to have prevented
      divergence (implicating a role for diversifying selection in the maintenance of
      the cline). Differentially expressed genes between S. aethnensis and S.
      chrysanthemifolius exhibit significantly higher genetic divergence relative to
      "expression invariant" controls, suggesting that species differences may in part
      be mediated by divergent selection on differentially expressed genes involved
      with altitude-related adaptation. The recent split time and the absence of fixed
      differences between these two ecologically distinct species suggest the rapid
      evolution to an altitudinal cline involving selection on both sequence and
      expression variation. 

PMID- 24094353
TI  - Parental age, gametic age, and inbreeding interact to modulate offspring
      viability in Drosophila melanogaster.
AB  - In principle, parental relatedness, parental age, and the age of parental gametes
      can all influence offspring fitness through inbreeding depression and the
      parental effects of organismal and postmeiotic gametic senescence. However,
      little is known about the extent to which these factors interact and contribute
      to fitness variation. Here, we show that, in Drosophila melanogaster, offspring
      viability is strongly affected by a three-way interaction between parental
      relatedness, parental age, and gametic age at successive developmental stages.
      Overall egg-to-adult viability was lowest for offspring produced with old gametes
      of related, young parents. This overall effect was largely determined at the pupa
      adult stage, although three-way interactions between parental relatedness,
      parental age and gametic age also explained variation in egg hatchability and
      larva-pupa survival. Controlling for the influence of parental and gametic age,
      we show that inbreeding depression is negligible for egg hatchability but
      significant at the larva-pupa and pupa-adult stages. At the pupa-adult stage,
      where offspring could be sexed, parental relatedness, parental age, and gametic
      age interacted differently in male and female offspring, with daughters suffering
      higher inbreeding depression than sons. Collectively, our results demonstrate
      that the architecture of offspring fitness is strongly influenced by a complex
      interaction between parental effects, inbreeding depression and offspring sex. 

PMID- 24094354
TI  - Ejaculate quality and constraints in relation to sperm competition levels among
      eutherian mammals.
AB  - The outcome of sperm competition is influenced by the relative quantity and
      quality of sperm among competing ejaculates. Whereas it is well established that
      individual ejaculate traits evolve rapidly under postcopulatory sexual selection,
      little is known about other factors that might influence the evolution of
      ejaculates. For example, the metabolic rate is likely to affect the sperm
      production rate and the cellular activity or metabolism of sperm, and it has
      recently been suggested to constrain the evolution of sperm length in large but
      not small mammals. I thus examined in eutherian mammals how ejaculate quality
      traits vary with one another and with testis mass, body size, and metabolism. I
      found all ejaculate traits to covary positively with one another and to increase
      with relative testis mass. When controlling for testis mass, small-bodied species
      showed superior sperm quality (but not sperm number). Furthermore, sperm motility
      and viability were positively associated with the mass-corrected metabolic rate,
      but the percentage of morphologically normal and acrosome-intact sperm were not.
      These results indicate that body size and the energy budget may also influence
      the evolution of ejaculate quality, although these influences appear to vary
      among traits. 

PMID- 24094355
TI  - Strategic adjustments in sperm production within and between two island
      populations of house mice.
AB  - Sperm production is physiologically costly. Consequently, males are expected to
      be prudent in their sperm production, and tailor their expenditure according to
      prevailing social conditions. Differences in sperm production have been found
      across island populations of house mice that differ in the level of selection
      from sperm competition. Here, we determined the extent to which these differences
      represent phenotypic plasticity and/or population divergence in sperm production.
      We sourced individuals from two populations at the extreme levels of sperm
      competition, and raised them under common-garden conditions while manipulating
      the social experience of developing males. Males from the high-sperm competition
      population produced more sperm and better quality sperm than did males from the
      low-sperm competition population. In addition, males reared under a perceived
      "risk" of sperm competition produced greater numbers of sperm than males reared
      with "no risk." However, our analyses revealed that phenotypic plasticity in
      sperm production was greater for individuals from the high-sperm competition
      population. Our results are thus consistent with both population divergence and
      phenotypic plasticity in sperm production, and suggest that population level of
      sperm competition might affect the degree of adaptive plasticity in sperm
      production in response to sperm competition risk. 

PMID- 24094356
TI  - Comment on Gohli et al. (2013): "Does promiscuity explain differences in levels
      of genetic diversity across passerine birds?".
AB  - Gohli et al. (2013) report a positive relationship between genetic diversity and
      promiscuity across passerine birds, and suggest that female promiscuity acts as a
      form of balancing selection, maintaining differences in genetic variation across
      species. This is an interesting hypothesis, but the enormous variation in genetic
      diversity present within species is not taken into account in their analyses.
      This, combined with a small sample size at several levels, makes the relationship
      between genetic diversity and promiscuity very difficult to interpret.
      Demonstrating that species-level differences in genetic diversity (if they occur
      at all) are affected by promiscuity would require a far more comprehensive study
      than is presently possible. 

PMID- 24094357
TI  - Promiscuity, sexual selection, and genetic diversity: a reply to Spurgin.
AB  - We recently reported a positive association between female promiscuity and
      genetic diversity across passerine birds, and launched the hypothesis that female
      promiscuity acts as a balancing selection, pressure maintaining genetic diversity
      in populations (Gohli et al.2013). Spurgin (2013) questions both our analyses and
      interpretations. While we agree that the hypothesis needs more comprehensive
      empirical testing, we find his specific points of criticism unjustified. In a
      more general perspective, we call for a more explicit recognition of female
      mating preferences as mechanisms of selection in population genetics theory.

PMID- 24094359
TI  - Improving job satisfaction of Chinese doctors: the positive effects of perceived
      organizational support and psychological capital.
AB  - OBJECTIVES: The huge population basic and the transformational changes to
      healthcare system in China have gained wide public attention in recent years.
      Along with these issues is a growing literature about doctor's job satisfaction;
      however, more is known about its negative related factors. Thus, this study was
      an attempt to assess the level of job satisfaction among Chinese doctors and to
      explore factors that enhance their job satisfaction. STUDY DESIGN: Cross
      sectional questionnaire-based survey. METHODS: A cross-sectional study was
      conducted during the period of September/October 2010. A questionnaire containing
      job satisfaction assessed by Minnesota Satisfaction Questionnaire (MSQ),
      demographic characteristics, work conditions, psychological capital (PsyCap) and
      perceived organizational support (POS) was distributed to 1300 registered doctors
      in Liaoning province. A total of 984 respondents became our subjects (effective
      response rate 75.7%). Hierarchical regression was performed to explore the
      factors associated with satisfaction. RESULTS: The average MSQ score was 65.86
      (level ranking for MSQ, 20-100) in our study population. Hierarchical regression
      analysis showed that POS (beta = 0.412, P < 0.001), PsyCap (beta = 0.255, P <
      0.001), incentive system (beta = 0.119, P < 0.001) and educational background
      (beta = 0.056, P = 0.042) were positively associated with job satisfaction.
      CONCLUSIONS: The job satisfaction of Chinese doctors was at a moderate level. POS
      and PsyCap seemed to be the most crucial factors in relation to job satisfaction.
      Therefore, efficient measures such as building a supportive work environment and
      developing doctors' PsyCap should be considered by health administrators in order
      to promote job satisfaction among Chinese doctors.

PMID- 24094358
TI  - Of fracture thresholds and bone mineral density reference data: does one size
      really fit all?
AB  - Men who fracture have greater mean bone mineral density (BMD) than women who
      fracture, and to some this suggests that BMD fracture "thresholds" are greater in
      men than women, justifying use of a male BMD reference standard. Others disagree
      and argue that because BMD distribution in men is right-shifted (higher) compared
      with women, anything that occurs with equal probability for men and women will
      occur at a greater mean BMD in men. If the latter is true, it supports using a
      common (female) BMD reference standard. We directly tested this latter principle
      and, indirectly, the validity of using a constant BMD reference standard, in
      51,326 women (3722 major fractures) and 4691 men (276 fractures), by comparing
      mean BMD in fracture vs nonfracture groups defined by sex, age, race and body
      mass index because these 4 factors affect both mean BMD and risk of fractures.
      Among those who fractured, mean BMD for all measurement sites were significantly
      greater in men vs women, youngest vs oldest, whites vs Asian, and heaviest vs the
      lightest (all p < 0.001). However, the same BMD pattern was seen in those who did
      not fracture and the absolute difference in BMD between those who fractured and
      those who did not was essentially constant regardless of sex, age, race, or
      weight class (all p-interaction nonsignificant). This finding suggests that use
      of a common reference standard for BMD (i.e., young white women) for men, and
      indeed all subgroups defined by osteoporosis risk factors, is reasonable and
      consistent with empiric observations.

PMID- 24094360
TI  - Spinal meningioma becoming symptomatic in the third trimester of pregnancy.
AB  - We report a rare case of a spinal meningioma leading to symptoms of spinal cord
      compression starting in the third trimester of gestation in a 32-year-old woman.
      Neurological symptoms, which continued to progress after the patient had given
      birth, were assumed to be sequelae of pregnancy and delivery, leading to a 6
      month delay in diagnosis and treatment. Fortunately a gross total resection was
      achieved at surgery and the patient recovered fully, without permanent
      consequences. Associated symptoms of spinal cord compression may be falsely
      attributed to pregnancy, both by the pregnant women and her treating physician. A
      high index of suspicion and thorough history and physical examination to identify
      red flags should be performed in patients with neurological symptoms.

PMID- 24094361
TI  - Primary extranodal marginal zone lymphoma involving the skull.
AB  - Extranodal marginal zone lymphoma (EMZL) is a rare cancer of B-lymphocyte origin
      typically found in the gastrointestinal tract within the mucosa-associated
      lymphoid tissue. EMZL accounts for 5% of all non-Hodgkin's lymphomas and has been
      reported to affect the central nervous system in several select case reports.
      Here, we describe a rare case of EMZL presenting as an isolated skull mass, and
      review current management of EMZL. To our knowledge, this is the first reported
      patient of isolated EMZL of the skull. 

PMID- 24094362
TI  - Use of the CRASH study prognosis calculator in patients with severe traumatic
      brain injury.

PMID- 24094363
TI  - [Autoimmune cytopenias: diagnosis before treatment].

PMID- 24094364
TI  - [Latent autoimmune diabetes in the young].

PMID- 24094365
TI  - [Prevalence of children exposed to tobacco smoke in vehicles: should measures be
      taken?].

PMID- 24094366
TI  - [Granulosa cell tumour in a patient with multiple enchondromatosis].

PMID- 24094367
TI  - [Prevalence of children under the age of 14 years exposed to secondhand smoke in
      vehicles in the city of Barcelona].

PMID- 24094368
TI  - Physiology and proteome responses of two contrasting rice mutants and their wild
      type parent under salt stress conditions at the vegetative stage.
AB  - Salinity is one of the major environmental limiting factors that affects growth
      and productivity of rice (Oryza sativa L.) worldwide. Rice is among the most
      sensitive crops to salinity, especially at early vegetative stages. In order to
      get a better understanding of molecular pathways affected in rice mutants showing
      contrasting responses to salinity, we exploited the power of 2-DE based
      proteomics to explore the proteome changes associated with salt stress response.
      Our physiological observations showed that standard evaluation system (SES)
      scores, Na+ and K+ concentrations in shoots and Na+/K+ ratio were significantly
      different in contrasting mutants under salt stress condition. Proteomics analysis
      showed that, out of 854 protein spots which were reproducibly detected, 67
      protein spots showed significant responses to salt stress. The tandem mass
      spectrometry analysis of these significantly differentially accumulated proteins
      resulted in identification of 34 unique proteins. These proteins are involved in
      various molecular processes including defense to oxidative stresses, metabolisms,
      photosynthesis, protein synthesis and processing, signal transduction. Several of
      the identified proteins were emerged as key participants in salt stress
      tolerance. The possible implication of salt responsive proteins in plant
      adaptation to salt stress is discussed.

PMID- 24094369
TI  - Status, influences and risk assessment of hexachlorocyclohexanes in agricultural
      soils across china.
AB  - Large amounts of hexaclorocyclohexanes (HCHs) were historically applied to
      Chinese soils. However, there has been limited information on the residue
      patterns of HCHs in soils at a national scale in China. In this study, surface
      soil samples were collected from agricultural fields across China, and the
      concentrations of HCHs and enantiomeric fractions (EFs) of alpha-HCH were
      measured. The results showed that the average concentrations of alpha-HCH, beta
      HCH, gamma-HCH, and total HCHs in Chinese agricultural soils were 0.190, 1.31,
      0.236, and 1.74 ng g(-1), respectively. Residues of HCHs likely originated from
      past usage of technical HCHs. The isomers of alpha-HCH and gamma-HCH tended to
      accumulate in the sites with lower total HCH concentrations, lower temperature,
      higher elevation, and less wet precipitation when compared to beta-HCH.
      Enantiomeric analysis showed a preferential degradation of (-)-alpha-HCH. Human
      health risks via various exposure routes to HCHs in soils were further estimated.
      Overall, the mean hazard index (HI) linked to noncarcinogenic risks was below 1,
      suggesting an absence of noncarcinogenic risks of HCHs in Chinese soils. In
      addition, the cancer risk values were all below 10(-4), which indicates low or
      very low risks. 

PMID- 24094370
TI  - Added value of fused somatostatin receptor imaging/magnetic resonance imaging in
      a rare case of paraganglioma of the urinary bladder.

PMID- 24094371
TI  - Standardized uptake value for (18)F-fluorodeoxyglucose is correlated with a high
      International Prognostic Index and the presence of extranodal involvement in
      patients with diffuse large B-cell lymphoma.
AB  - The aim of this study was to evaluate whether the maximum standardized uptake
      value (SUVmax) of (18)F-fluorodeoxyglucose (FDG) correlates with the
      International Prognostic Index (IPI) and the presence of extranodal involvement
      in patients with Diffuse Large B-Cell Lymphoma (DLBCL). MATERIAL AND METHODS: 77
      patients (age: 57.2+/-18.5, 40F, 37M) with DLBCL who underwent FDG PET/CT for
      initial staging were included. SUVmax of the predominant lesions were compared to
      Ann Arbor stage, IPI scores, the presence of extranodal involvement and the
      number extranodal sites. RESULTS: PET/CT detected nodal (n:25) and extranodal
      involvement (n:52) in all the patients. In 27 patients, extranodal disease could
      only be detected by PET. SUVmax of the predominant lesion in patients with
      extranodal disease was significantly higher than that of the patients who had
      only nodal disease (25+/-12 vs. 15.3+/-10 respectively, p=0.001). SUVmax
      significantly correlated with IPI scores; the average SUVmax was significantly
      correlated with the IPI: Mean SUVmax of the predominant lesion was 13.9+/-9.5 in
      patients with low risk (IPI=0-1), 14.2+/-8.8 in low-intermediate risk group
      (IPI=2) whereas 26.6+/-9.5 in high-intermediate risk group (IPI=3) and 25+/-13.6
      in high risk group patients (IPI=4-5) (p=0.002). SUVmax was not correlated with
      clinical stage, the number of extranodal sites and serum LDH levels. CONCLUSION:
      FDG uptake correlates with IPI and the presence of extranodal involvement in
      DLBCL. PET is a powerful method to detect extranodal disease in DLBCL. The
      correlation of SUVmax with these prognostic factors may highlight the importance
      of pretreatment FDG uptake as a metabolic marker of poor prognosis for patients
      with DLBCL.

PMID- 24094372
TI  - [18F-FDG-PET-CT in soft tissue sarcomas: when to image?].

PMID- 24094373
TI  - Clinical validation of the planar radionuclide ventriculography in patients with
      right ventricular dysfunction.
AB  - OBJECTIVES: Gated radionuclide ventriculography (RNV) may be used for the
      evaluation of the right ventricular function. However, the accuracy of the method
      should be clinically validated in patients suffering from diseases with specific
      pathology of the right ventricle (RV) and with possible left ventricular (LV)
      interaction. METHODS: Three groups of 15 patients each, diagnosed with
      arrhythmogenic right ventricular dysplasia (ARVD), pulmonary artery hypertension
      (PAH) or atrial septal defect (ASD) were compared to a group of normal subjects.
      The parameters for both ventricles were evaluated separately (ejection fractions:
      LVEF and RVEF, and intraventricular synchronism quantified as phase standard
      deviation: LVPSD and RVPSD) as well as the relation or interdependence of the
      right to left ventricle (RV/LV volume ratio, LV/RV ejection fraction and stroke
      volume ratios, and interventricular synchronism). All the variables as a whole
      were analyzed to identify groups of patients according to their functional
      behaviour. RESULTS: Significant differences were found between the patients and
      control group for the RV function while the LV function remained mostly within
      normal limits. When the RV function was considered, the control group and ASD
      patient group showed differences regarding the ARVD and PAH patients. On
      evaluating the RV/LV ratios, differences were found between the control group and
      the ASD group. In the PAH patients, LV function showed differences in relation to
      the rest of the groups. CONCLUSION: RNV is a reliable clinical tool to evaluate
      RV function in patients with RV abnormality.

PMID- 24094374
TI  - A case of optic neuritis incidentally detected by somatostatin receptor
      scintigraphy.

PMID- 24094375
TI  - [Utility of single photon emission computed tomography-computed tomography in
      selective sentinel lymph node biopsy in patients with melanoma].
AB  - OBJECTIVE: To assess the contribution of SPECT-CT lymphoscintigraphy in selective
      sentinel lymph node biopsy (SLNB) in patients with newly diagnosed malignant
      melanoma. MATERIAL AND METHODS: A prospective study was made between July 2009
      and October 2010. It included 63 patients diagnosed with melanoma (32 men and 31
      women) with mean age of 55 years (range: 25-88) and inclusion criteria for SLNB.
      The melanomas were located as follows: 28 in trunk, 5 in head and neck, 16 in
      upper limbs and 17 in lower limbs. Three patients had two melanomas. Preoperative
      lymphoscintigraphy was performed after pericicatricial/perilesional injection of
      74MBq of (99m)Tc-labeled nanocolloid human serum albumin, obtaining early planar
      images, late whole body study and sectorial images and SPECT-CT in the area of
      interest. Planar scintigraphy findings were compared with SPECT-CT. RESULTS: The
      sentinel node (SN) was localized by planar imaging in 62/63 (98%) of patients.
      SPECT-CT study located the SN in all the patients with a detection rate of 100%.
      The number of SNs detected with SPECT-CT was higher than with the planar study in
      27 patients. The SPECT-CT provided additional information (change in location
      and/or in its accuracy in the localization of location uncertain SN) in 14/63
      (22.2%) patients, involving changes in the surgical approach and lymph node
      staging. CONCLUSION: SPECT-CT detects a higher number of SN than planar
      lymphoscintigraphy in patients with melanoma. Its contribution is more relevant
      in the melanomas located on the trunk, head and neck. SPECT-CT modified the SN
      location by 22% compared to planar scan findings, facilitating a correct surgical
      approach.

PMID- 24094376
TI  - Culture-based diagnostic microbiology in cystic fibrosis: can we simplify the
      complexity?
AB  - Cystic fibrosis (CF) diagnostic microbiology has evolved from a focus on
      Staphylococcus aureus as primary pathogen to identification of the contribution
      of Pseudomonas aeruginosa and other non-fermenting gram negatives; studies of the
      lung microbiome have added new complexity. This review summarizes state-of-the
      art culture methods and makes recommendations for addition of non-culture based
      methods in the diagnostic laboratory. Plating on selective media is recommended,
      with organism identification by matrix assisted laser desorption-time of flight
      mass spectroscopy and real-time polymerase chain reaction (PCR) supplanting both
      biochemical identification and other less accurate and more time-consuming
      molecular methods. Conventional antibiotic susceptibility testing, possibly at
      less frequent intervals, remains the standard but more CF-relevant methods may
      arise in the future. There is a role for direct identification of organisms in
      clinical samples using quantitative real-time PCR, next generation sequencing,
      and metagenomic studies for the re-examination of samples that do not yield
      traditional CF pathogens. 

PMID- 24094377
TI  - Necrotizing soft tissue infections.
AB  - Necrotizing soft tissue infections (NSTIs) are infrequent yet highly lethal
      infections, and a high index of suspicion is required for early diagnosis.
      Diagnosing NSTIs early can be challenging, and knowledge of the available tools
      is essential to provide appropriate treatment. The mainstay of treatment is early
      and complete surgical debridement combined with antimicrobial therapy, close
      monitoring with further debridement as needed, and physiologic support. Mortality
      continues to be high, and delayed surgical treatment is the most important risk
      factor. For the long-term recovery of patients with NSTI, providing early
      physiologic and nutritional support and physical rehabilitation is essential. 

PMID- 24094378
TI  - Life-threatening infections in medically immunocompromised patients.
AB  - Chronic medical diseases, such as diabetes, chronic obstructive pulmonary
      disease, chronic kidney disease, cirrhosis, and heart failure, are associated
      with various immune defects that make affected patients prone to specific
      infections. This review discusses the epidemiology, pathogenesis, antimicrobial
      and surgical management, supportive care, and outcome of life-threatening
      infections associated with common chronic medical diseases. 

PMID- 24094379
TI  - Overview of severe Clostridium difficile infection.
AB  - Clostridium difficile is an anaerobic, spore-forming, gram-positive bacillus that
      can produce severe colitis resulting in death. There has been an overall increase
      in the incidence of Clostridium difficile-associated disease and, particularly,
      an increase in the more virulent forms of the disease. Treatment of severe C
      difficile infection includes management of severe sepsis and shock, pathogen
      directed antibiotic therapy, and, in selected cases, surgical intervention.
      Ultimately, prevention is the key to limiting the devastating effects of this
      microorganism. 

PMID- 24094380
TI  - Vancomycin-resistant enterococci.
AB  - Vancomycin-resistant enterococci (VRE) consist mainly of Enterococcus faecalis
      and E faecium, the latter mostly hospital-acquired. In addition, E gallinarum and
      E casseliflavus are intrinsically vancomycin-resistant and are community
      acquired. VRE have become common in many hospitals throughout the world and, once
      established, are very difficult to eradicate. VRE are difficult to treat;
      therefore, infection control measures in hospitals are of prime importance in
      preventing the establishment of these pathogens. Most severe VRE infections will
      need combination therapy because many of the effective antimicrobial agents, when
      used alone, have only a bacteriostatic effect.

PMID- 24094381
TI  - Why Candida sepsis should matter to ICU physicians.
AB  - The incidence of candidemia and invasive Candida infections has increased
      substantially over the last 2 decades. These infections are associated with risk
      factors that characterize intensive care unit patients. Candidemia and invasive
      Candida are highly morbid and associated with significantly increased mortality.
      Outcomes in the intensive care setting depend on physician awareness and rapid
      intervention. The epidemiology of the disease, its diagnostic challenges, and
      management strategies, including prophylactic, preemptive, and definitive
      therapeutic approaches, are presented herein. 

PMID- 24094382
TI  - Management of severe malaria in the intensive care unit.
AB  - Severe malaria is a medical emergency requiring early intervention to prevent
      death. This article highlights key aspects of the management of severe malaria
      syndromes in the intensive care unit, with a focus on individual case management
      of imported malaria. Key differences in the presentation, management, and
      outcomes of severe malaria by endemicity and by age group are emphasized. In all
      groups with severe malaria, intravenous artesunate is the antimalarial agent of
      choice. This article discusses specific antimalarial therapies, optimal
      supportive management strategies, differences from strategies for bacterial
      sepsis, and trials of adjunctive therapy for severe malaria in humans. 

PMID- 24094383
TI  - Prevention, diagnosis, and management of surgical site infections: relevant
      considerations for critical care medicine.
AB  - Surgical site infection complicates 2% to 5% of all operative procedures. Many of
      the risk factors for the development of a surgical site infection (eg, old age,
      major comorbidity, emergency surgery) are present in patients typically requiring
      postoperative admission to the intensive care unit. This article reviews the risk
      factors and measures to prevent surgical site infection and diagnostic and
      management considerations relevant to critical care medicine. 

PMID- 24094384
TI  - Resistant gram-negative infections.
AB  - This article reviews the global crisis of resistant gram-negative bacilli in the
      intensive care unit. The authors discuss drugs used for treating these infections
      and the different strategies used to maximize the effect of antimicrobials. 

PMID- 24094385
TI  - Infective endocarditis in the intensive care unit.
AB  - Infective endocarditis has many facets and various expressions depending on the
      site of infection, microorganism, underlying heart lesion, immune status of the
      host, and remote effects such as emboli, organ dysfunction, and the condition of
      the host. Diagnosis depends on meticulous clinical examination, blood cultures
      results, and echocardiographic findings. The management of the patient with
      endocarditis in the intensive care unit is complex and needs a multidisciplinary
      team, including an intensivist, cardiologist, experienced echocardiologist,
      infectious diseases specialist, and cardiac surgeon. The medical and surgical
      management of such patients is complex, and timely decisions are important. 

PMID- 24094386
TI  - Life-threatening infection in transplant recipients.
AB  - Modern post-transplant care pathways commonly encompass periods of critical care
      support. Infectious events account for many of these interactions making critical
      care physicians integral members of multidisciplinary transplant teams. Despite
      continuing advances in clinical care and infection prophylaxis, the morbidity and
      mortality attributable to infection post-transplant remains considerable.
      Emerging entities constantly add to the breadth of potential opportunistic
      pathogens. Individualized risk assessments, rapid and thorough diagnostic
      evaluation, and prompt initiation of appropriate antimicrobial therapies are
      essential. The approach to managing transplant recipients with infection in
      critical care is discussed and common and emerging opportunistic pathogens are
      reviewed. 

PMID- 24094387
TI  - Bacterial meningitis and other nonviral infections of the nervous system.
AB  - Bacteria and fungi, owing to their intrinsic properties and the host responses
      they produce, result in relatively specific clinical syndromes when they infect
      the central nervous system. The infecting organism may produce symptoms and signs
      by interfering with the function of the nervous system tissue being invaded or
      compressed. The definitive treatment of central nervous system infection depends
      on correct identification and antimicrobial treatment of the infecting organism,
      relief of excessive pressure or mass effect that it exerts, and modulation of the
      host's immune response to allow clearance of the organism while minimizing
      excessive inflammation. 

PMID- 24094388
TI  - Catheter-related and infusion-related sepsis.
AB  - This article focuses on the pathogenesis, diagnosis, prevention, and management
      of infectious complications of intravascular cannulation and fluid infusion.
      Although continuous vascular access is one of the most essential modalities in
      modern-day medicine, there is a substantial and underappreciated potential for
      producing iatrogenic complications, the most important of which is blood-borne
      infection. Clinicians often fail to consider the diagnosis of infusion-related
      sepsis because clinical signs and symptoms are indistinguishable from bloodstream
      infections arising from other sites. Understanding and consideration of the risk
      factors predisposing patients to infusion-related infections may guide the
      development and implementation of control measures for prevention. 

PMID- 24094389
TI  - Abdominal catastrophes in the intensive care unit setting.
AB  - Patients in the setting of the intensive care unit can develop intra-abdominal
      complications that may worsen outcome. Clinical suspicion of such complications
      coupled with early diagnosis and treatment may reduce morbidity and mortality
      associated with these processes. This article addresses the diagnosis and
      management of some of the common causes of intra-abdominal catastrophes. 

PMID- 24094390
TI  - Other viral pneumonias: coronavirus, respiratory syncytial virus, adenovirus,
      hantavirus.
AB  - Severe viral pneumonia is an increasing problem among adults. The incidence and
      number of viruses known to cause pneumonia and respiratory failure have also
      expanded in recent years. This article provides an overview of severe respiratory
      disease caused by coronavirus, respiratory syncytial virus, adenovirus, and
      hantavirus. These emerging pathogens are easily overlooked and timely diagnosis
      requires a high index of suspicion and confirmation by molecular testing.
      Management of individual cases is mainly supportive and requires institution of
      appropriate infection control measures. Vaccines and effective therapeutics for
      these potentially devastating respiratory viruses are urgently required. 

PMID- 24094391
TI  - Influenza and endemic viral pneumonia.
AB  - Viruses are a common and important cause of severe community-acquired pneumonia,
      and may lead to severe respiratory disease and admission to the intensive care
      unit. Influenza is the most common virus associated with severe viral pneumonia,
      although other important causes include respiratory syncytial virus, adenovirus,
      metapneumonia virus, and coronaviruses. Viral pneumonias tend to have a seasonal
      predilection and are often preceded by a typical viral prodrome. This article
      focuses on severe influenza pneumonia, including the 2009 H1N1 pandemic, and
      briefly discusses other causes of severe respiratory disease of viral etiology. 

PMID- 24094393
TI  - Fast sampling of A-to-B protein global conformational transitions: from Galileo
      Galilei to Monte Carlo anisotropic network modeling.

PMID- 24094394
TI  - Intracellular dynamics of bacterial proteins are revealed by super-resolution
      microscopy.

PMID- 24094395
TI  - Will the real single HCN channel please stand up?

PMID- 24094396
TI  - Mechanisms of beat-to-beat regulation of cardiac pacemaker cell function by Ca2+
      cycling dynamics.
AB  - Whether intracellular Ca(2+) cycling dynamics regulate cardiac pacemaker cell
      function on a beat-to-beat basis remains unknown. Here we show that under
      physiological conditions, application of low concentrations of caffeine (2-4 mM)
      to isolated single rabbit sinoatrial node cells acutely reduces their spontaneous
      action potential cycle length (CL) and increases Ca(2+) transient amplitude for
      several cycles. Numerical simulations, using a modified Maltsev-Lakatta coupled
      clock model, faithfully reproduced these effects, and also the effects of CL
      prolongation and dysrhythmic spontaneous beating (produced by cytosolic Ca(2+)
      buffering) and an acute CL reduction (produced by flash-induced Ca(2+) release
      from a caged Ca(2+) buffer), which we had reported previously. Three contemporary
      numerical models (including the original Maltsev-Lakatta model) failed to
      reproduce the experimental results. In our proposed new model, Ca(2+) releases
      acutely change the CL via activation of the Na(+)/Ca(2+) exchanger current. Time
      dependent CL reductions after flash-induced Ca(2+) releases (the memory effect)
      are linked to changes in Ca(2+) available for pumping into sarcoplasmic reticulum
      which, in turn, changes the sarcoplasmic reticulum Ca(2+) load, diastolic Ca(2+)
      releases, and Na(+)/Ca(2+) exchanger current. These results support the idea that
      Ca(2+) regulates CL in cardiac pacemaker cells on a beat-to-beat basis, and
      suggest a more realistic numerical mechanism of this regulation.

PMID- 24094397
TI  - The role of vimentin intermediate filaments in cortical and cytoplasmic
      mechanics.
AB  - The mechanical properties of a cell determine many aspects of its behavior, and
      these mechanics are largely determined by the cytoskeleton. Although the
      contribution of actin filaments and microtubules to the mechanics of cells has
      been investigated in great detail, relatively little is known about the
      contribution of the third major cytoskeletal component, intermediate filaments
      (IFs). To determine the role of vimentin IF (VIF) in modulating intracellular and
      cortical mechanics, we carried out studies using mouse embryonic fibroblasts
      (mEFs) derived from wild-type or vimentin(-/-) mice. The VIFs contribute little
      to cortical stiffness but are critical for regulating intracellular mechanics.
      Active microrheology measurements using optical tweezers in living cells reveal
      that the presence of VIFs doubles the value of the cytoplasmic shear modulus to
      ~10 Pa. The higher levels of cytoplasmic stiffness appear to stabilize organelles
      in the cell, as measured by tracking endogenous vesicle movement. These studies
      show that VIFs both increase the mechanical integrity of cells and localize
      intracellular components.

PMID- 24094398
TI  - Molecular dynamics simulations of homo-oligomeric bundles embedded within a lipid
      bilayer.
AB  - Using molecular dynamics simulations, we studied the structure, interhelix
      interactions, and dynamics of transmembrane proteins. Specifically, we
      investigated homooligomeric helical bundle systems consisting of synthetic alpha
      helices with either the sequence Ac-(LSLLLSL)3-NH2 (LS2) or Ac-(LSSLLSL)3-NH2
      (LS3). The LS2 and LS3 helical peptides are designed to have amphipathic
      characteristics that form ion channels in membrane. We simulated bundles
      containing one to six peptides that were embedded in palmitoyl-oleoyl
      phosphatidylcholine (POPC) lipid bilayer and placed between two lamellae of
      water. We aim to provide a fundamental understanding of how amphipathic helical
      peptides interact with each other and their dynamical behaviors in different
      homooligomeric states. To understand structural properties, we examined the helix
      lengths, tilt angles of individual helices and the entire bundle, interhelix
      distances, interhelix cross-angles, helix hydrophobic-to-hydrophilic vector
      projections, and the average number of interhelix hydrophilic (serine-serine)
      contacts lining the pore of the transmembrane channel. To analyze dynamical
      properties, we calculated the rotational autocorrelation function of each helix
      and the cross-correlation of the rotational velocity between adjacent helices.
      The observed structural and dynamical characteristics show that higher order
      bundles containing four to six peptides are composed of multiple lower order
      bundles of one to three peptides. For example, the LS2 channel was found to be
      stable in a tetrameric bundle composed of a "dimer of dimers." In addition, we
      observed that there is a minimum of two strong hydrophilic contacts between a
      pair of adjacent helices in the dimer to tetramer systems and only one strong
      hydrophilic interhelix contact in helix pairs of the pentamer and hexamer
      systems. We believe these results are general and can be applied to more complex
      ion channels, providing insight into ion channel stability and assembly.

PMID- 24094399
TI  - Elementary functional properties of single HCN2 channels.
AB  - Hyperpolarization-activated cyclic-nucleotide-gated (HCN) channels are tetramers
      that evoke rhythmic electrical activity in specialized neurons and cardiac cells.
      These channels are activated by hyperpolarizing voltage, and the second messenger
      cAMP can further enhance the activation. Despite the physiological importance of
      HCN channels, their elementary functional properties are still unclear. In this
      study, we expressed homotetrameric HCN2 channels in Xenopus oocytes and performed
      single-channel experiments in patches containing either one or multiple channels.
      We show that the single-channel conductance is as low as 1.67 pS and that channel
      activation is a one-step process. We also observed that the time between the
      hyperpolarizing stimulus and the first channel opening, the first latency,
      determines the activation process alone. Notably, at maximum hyperpolarization,
      saturating cAMP drives the channel to open for unusually long periods. In
      particular, at maximum activation by hyperpolarization and saturating cAMP, the
      open probability approaches unity. In contrast to other reports, no evidence of
      interchannel cooperativity was observed. In conclusion, single HCN2 channels
      operate only with an exceptionally low conductance, and both activating stimuli,
      voltage and cAMP, exclusively control the open probability. 

PMID- 24094400
TI  - The properties of chondrocyte membrane reservoirs and their role in impact
      induced cell death.
AB  - Impact loading of articular cartilage causes extensive chondrocyte death. Cell
      membranes have a limited elastic range of 3-4% strain but are protected from
      direct stretch during physiological loading by their membrane reservoir, an
      intricate pattern of membrane folds. Using a finite-element model, we suggested
      previously that access to the membrane reservoir is strain-rate-dependent and
      that during impact loading, the accessible membrane reservoir is drastically
      decreased, so that strains applied to chondrocytes are directly transferred to
      cell membranes, which fail when strains exceed 3-4%. However, experimental
      support for this proposal is lacking. The purpose of this study was to measure
      the accessible membrane reservoir size for different membrane strain rates using
      membrane tethering techniques with atomic force microscopy. We conducted atomic
      force spectroscopy on isolated chondrocytes (n = 87). A micron-sized cantilever
      was used to extract membrane tethers from cell surfaces at constant pulling
      rates. Membrane tethers could be identified as force plateaus in the resulting
      force-displacement curves. Six pulling rates were tested (1, 5, 10, 20, 40, and
      80 MUm/s). The size of the membrane reservoir, represented by the membrane tether
      surface areas, decreased exponentially with increasing pulling rates. The current
      results support our theoretical findings that chondrocytes exposed to impact
      loading die because of membrane ruptures caused by high tensile membrane strain
      rates.

PMID- 24094401
TI  - Antibody-induced acetylcholine receptor clusters inhabit liquid-ordered and
      liquid-disordered domains.
AB  - The distribution of nicotinic acetylcholine receptor (AChR) clusters at the cell
      membrane was studied in CHO-K1/A5 cells using fluorescence microscopy. Di-4
      ANEPPDHQ, a fluorescent probe that differentiates between liquid-ordered (Lo) and
      liquid-disordered (Ld) phases in model membranes, was used in combination with
      monoclonal anti-AChR antibody labeling of live cells, which induces AChR
      clustering. The so-called generalized polarization (GP) of di-4-ANEPPDHQ was
      measured in regions of the cell-surface membrane associated with or devoid of
      antibody-induced AChR clusters, respectively. AChR clusters were almost equally
      distributed between Lo and Ld domains, independently of receptor surface levels
      and agonist (carbamoylcholine and nicotine) or antagonist (alpha-bungarotoxin)
      binding. Cholesterol depletion diminished the cell membrane mean di-4-ANEPPDHQ GP
      and the number of AChR clusters associated with Ld membrane domains increased
      concomitantly. Depolymerization of the filamentous actin cytoskeleton by
      Latrunculin A had the opposite effect, with more AChR clusters associated with Lo
      domains. AChR internalized via small vesicles having lower GP and lower
      cholesterol content than the surface membrane. Upon cholesterol depletion, only
      12% of the AChR-containing vesicles costained with the fluorescent cholesterol
      analog fPEG-cholesterol, i.e., AChR endocytosis was essentially dissociated from
      that of cholesterol. In conclusion, the distribution of AChR submicron-sized
      clusters at the cell membrane appears to be regulated by cholesterol content and
      cytoskeleton integrity.

PMID- 24094402
TI  - Interactions between fengycin and model bilayers quantified by coarse-grained
      molecular dynamics.
AB  - Bacteria, particularly of the genus Bacillus, produce a wide variety of
      antifungal compounds. They act by affecting the lipid bilayers of fungal
      membranes, causing curvature-induced strain and eventual permeabilization. One
      class of these, known as fengycins, has been commercialized for treating
      agricultural infections and shows some promise as a possible antifungal
      pharmaceutical. Understanding the mechanism by which fengycins damage lipid
      bilayers could prove useful to the future development of related antifungal
      treatments. In this work, we present multi-microsecond-long simulations of
      fengycin interacting with different lipid bilayer systems. We see fengycin
      aggregation and uncover a clear aggregation pattern that is partially influenced
      by bilayer composition. We also quantify some local bilayer perturbations caused
      by fengycin binding, including curvature of the lipid bilayer and local
      electrostatic-driven reorganization.

PMID- 24094403
TI  - Effects of ATP and actin-filament binding on the dynamics of the myosin II S1
      domain.
AB  - Actin and myosin interact with one another to perform a variety of cellular
      functions. Central to understanding the processive motion of myosin on actin is
      the characterization of the individual states along the mechanochemical cycle. We
      present an all-atom molecular dynamics simulation of the myosin II S1 domain in
      the rigor state interacting with an actin filament. We also study actin-free
      myosin in both rigor and post-rigor conformations. Using all-atom level and
      coarse-grained analysis methods, we investigate the effects of myosin binding on
      actin, and of actin binding on myosin. In particular, we determine the domains of
      actin and myosin that interact strongly with one another at the actomyosin
      interface using a highly coarse-grained level of resolution, and we identify a
      number of salt bridges and hydrogen bonds at the interface of myosin and actin.
      Applying coarse-grained analysis, we identify differences in myosin states
      dependent on actin-binding, or ATP binding. Our simulations also indicate that
      the actin propeller twist-angle and nucleotide cleft-angles are influenced by
      myosin at the actomyosin interface. The torsional rigidity of the myosin-bound
      filament is also calculated, and is found to be increased compared to previous
      simulations of the free filament.

PMID- 24094404
TI  - Single-molecule analysis of the rotation of F1-ATPase under high hydrostatic
      pressure.
AB  - F1-ATPase is the water-soluble part of ATP synthase and is an ATP-driven rotary
      molecular motor that rotates the rotary shaft against the surrounding stator
      ring, hydrolyzing ATP. Although the mechanochemical coupling mechanism of F1
      ATPase has been well studied, the molecular details of individual reaction steps
      remain unclear. In this study, we conducted a single-molecule rotation assay of
      F1 from thermophilic bacteria under various pressures from 0.1 to 140 MPa. Even
      at 140 MPa, F1 actively rotated with regular 120 degrees  steps in a
      counterclockwise direction, showing high conformational stability and retention
      of native properties. Rotational torque was also not affected. However, high
      hydrostatic pressure induced a distinct intervening pause at the ATP-binding
      angles during continuous rotation. The pause was observed under both ATP-limiting
      and ATP-saturating conditions, suggesting that F1 has two pressure-sensitive
      reactions, one of which is evidently ATP binding. The rotation assay using a
      mutant F1(betaE190D) suggested that the other pressure-sensitive reaction occurs
      at the same angle at which ATP binding occurs. The activation volumes were
      determined from the pressure dependence of the rate constants to be +100 A(3) and
      +88 A(3) for ATP binding and the other pressure-sensitive reaction, respectively.
      These results are discussed in relation to recent single-molecule studies of F1
      and pressure-induced protein unfolding.

PMID- 24094405
TI  - Global transitions of proteins explored by a multiscale hybrid methodology:
      application to adenylate kinase.
AB  - Efficient and accurate mapping of transition pathways is a challenging problem in
      allosteric proteins. We propose here a to our knowledge new methodology called
      collective molecular dynamics (coMD). coMD takes advantage of the collective
      modes of motions encoded by the fold, simultaneously evaluating the interactions
      and energetics via a full-atomic MD simulation protocol. The basic approach is to
      deform the structure collectively along the modes predicted by the anisotropic
      network model, upon selecting them via a Monte Carlo/Metropolis algorithm from
      among the complete pool of all accessible modes. Application to adenylate kinase,
      an allosteric enzyme composed of three domains, CORE, LID, and NMP, shows that
      both open-to-closed and closed-to-open transitions are readily sampled by coMD,
      with large-scale motions of the LID dominating. An energy-barrier crossing occurs
      during the NMP movements. The energy barrier originates from a switch between the
      salt bridges K136-D118 at the LID-CORE interface and K57-E170 and D33-R156 at the
      CORE-NMP and LID-NMP interfaces, respectively. Despite its simplicity and
      computing efficiency, coMD yields ensembles of transition pathways in close
      accord with detailed full atomic simulations, lending support to its utility as a
      multiscale hybrid method for efficiently exploring the allosteric transitions of
      multidomain or multimeric proteins.

PMID- 24094406
TI  - Positive and negative design for nonconsensus protein-DNA binding affinity in the
      vicinity of functional binding sites.
AB  - Recent experiments provide an unprecedented view of protein-DNA binding in yeast
      and human genomes at single-nucleotide resolution. These measurements, performed
      over large cell populations, show quite generally that sequence-specific
      transcription regulators with well-defined protein-DNA consensus motifs bind only
      a fraction among all consensus motifs present in the genome. Alternatively,
      proteins in vivo often bind DNA regions lacking known consensus sequences. The
      rules determining whether a consensus motif is functional remain incompletely
      understood. Here we predict that genomic background surrounding specific protein
      DNA binding motifs statistically modulates the binding of sequence-specific
      transcription regulators to these motifs. In particular, we show that
      nonconsensus protein-DNA binding in yeast is statistically enhanced, on average,
      around functional Reb1 motifs that are bound as compared to nonfunctional Reb1
      motifs that are unbound. The landscape of nonconsensus protein-DNA binding around
      functional CTCF motifs in human demonstrates a more complex behavior. In
      particular, human genomic regions characterized by the highest CTCF occupancy,
      show statistically reduced level of nonconsensus protein-DNA binding. Our
      findings suggest that nonconsensus protein-DNA binding is fine-tuned around
      functional binding sites using a variety of design strategies.

PMID- 24094407
TI  - Cyclic N-terminal loop of amylin forms non amyloid fibers.
AB  - We report for the first time, to our knowledge, that the N-terminal loop (N_loop)
      of amylin (islet amyloid polypeptide (IAPP) residues 1-8) forms extremely long
      and stable non-beta-sheet fibers in solution under the same conditions in which
      human amylin (hIAPP) forms amyloid fibers. This observation applies to the
      cyclic, oxidized form of the N_loop but not to the linear, reduced form, which
      does not form fibers. Our findings indicate a potential role of direct N_loop
      N_loop interactions in hIAPP aggregation, which has not been previously explored,
      with important implications for the mechanism of hIAPP amyloid fiber formation,
      the inhibitory action of IAPP variants, and the competition between ordered and
      disordered aggregation in peptides of the calcitonin peptide family.

PMID- 24094408
TI  - Dynamics of nuclear receptor Helix-12 switch of transcription activation by
      modeling time-resolved fluorescence anisotropy decays.
AB  - Nuclear hormone receptors (NRs) are major targets for pharmaceutical development.
      Many experiments demonstrate that their C-terminal Helix (H12) is more flexible
      in the ligand-binding domains (LBDs) without ligand, this increased mobility
      being correlated with transcription repression and human diseases. Crystal
      structures have been obtained in which the H12 is extended, suggesting the
      possibility of large amplitude H12 motions in solution. However, these structures
      were interpreted as possible crystallographic artifacts, and thus the microscopic
      nature of H12 movements is not well known. To bridge the gap between experiments
      and molecular models and provide a definitive picture of H12 motions in solution,
      extensive molecular dynamics simulations of the peroxisome proliferator-activated
      receptor-gamma LBD, in which the H12 was bound to a fluorescent probe, were
      performed. A direct comparison of the modeled anisotropy decays to time-resolved
      fluorescence anisotropy experiments was obtained. It is shown that the decay
      rates are dependent on the interactions of the probe with the surface of the
      protein, and display little correlation with the flexibility of the H12.
      Nevertheless, for the probe to interact with the surface of the LBD, the H12 must
      be folded over the body of the LBD. Therefore, the molecular mobility of the H12
      should preserve the globularity of the LBD, so that ligand binding and
      dissociation occur by diffusion through the surface of a compact receptor. These
      results advance the comprehension of both ligand-bound and ligand-free receptor
      structures in solution, and also guide the interpretation of time-resolved
      anisotropy decays from a molecular perspective, particularly by the use of
      simulations.

PMID- 24094409
TI  - The role of cross-chain ionic interactions for the stability of collagen model
      peptides.
AB  - The contribution of ionic interactions to the stability of the collagen triple
      helix was studied using molecular dynamics (MD) simulations and biophysical
      methods. To this end, we examined the stability of a host-guest collagen model
      peptide, Ac-GPOGPOGPYGXOGPOGPO-NH2, substituting KGE, KGD, EGK, and DGK for the
      YGX sequence. All-atom, implicit solvent MD simulations show that the fraction of
      cross-chain ionic interactions formed is different, with the most pronounced in
      the KGE and KGD sequences, and the least in the DGK sequence. To test whether the
      fraction of cross-chain ionic interactions correlates with the stability,
      experimental measurements of thermostability were done using differential
      scanning calorimetry and circular dichroism spectroscopy. It was found that the
      melting temperature is very similar for KGE and KGD peptides, whereas the EGK
      peptide has lower thermostability and the DGK peptide is the least thermostable.
      A novel, to our knowledge, computational protocol termed temperature-scan MD was
      applied to estimate the relative stabilities of the peptides from MD simulations.
      We found an excellent correlation between transition temperatures obtained from
      temperature-scan MD and those measured experimentally. These results suggest the
      importance of cross-chain ionic interactions for the stability of collagen triple
      helix and confirm the utility of MD simulations in predicting interactions and
      stability in this system.

PMID- 24094410
TI  - Quantification of excluded volume effects on the folding landscape of Pseudomonas
      aeruginosa apoazurin in vitro.
AB  - Proteins fold and function inside cells that are crowded with macromolecules.
      Here, we address the role of the resulting excluded volume effects by in vitro
      spectroscopic studies of Pseudomonas aeruginosa apoazurin stability (thermal and
      chemical perturbations) and folding kinetics (chemical perturbation) as a
      function of increasing levels of crowding agents dextran (sizes 20, 40, and 70
      kDa) and Ficoll 70. We find that excluded volume theory derived by Minton
      quantitatively captures the experimental effects when crowding agents are modeled
      as arrays of rods. This finding demonstrates that synthetic crowding agents are
      useful for studies of excluded volume effects. Moreover, thermal and chemical
      perturbations result in free energy effects by the presence of crowding agents
      that are identical, which shows that the unfolded state is energetically the same
      regardless of method of unfolding. This also underscores the two-state
      approximation for apoazurin's unfolding reaction and suggests that thermal and
      chemical unfolding experiments can be used in an interchangeable way. Finally, we
      observe increased folding speed and invariant unfolding speed for apoazurin in
      the presence of macromolecular crowding agents, a result that points to unfolded
      state perturbations. Although the absolute magnitude of excluded volume effects
      on apoazurin is only on the order of 1-3 kJ/mol, differences of this scale may be
      biologically significant.

PMID- 24094411
TI  - Mapping the interactions between the Alzheimer's Abeta-peptide and human serum
      albumin beyond domain resolution.
AB  - Human serum albumin (HSA) is a potent inhibitor of Abeta self-association and
      this novel, to our knowledge, function of HSA is of potential therapeutic
      interest for the treatment of Alzheimer's disease. It is known that HSA interacts
      with Abeta oligomers through binding sites evenly partitioned across the three
      albumin domains and with comparable affinities. However, as of this writing, no
      information is available on the HSA-Abeta interactions beyond domain resolution.
      Here, we map the HSA-Abeta interactions at subdomain and peptide resolution. We
      show that each separate subdomain of HSA domain 3 inhibits Abeta self
      association. We also show that fatty acids (FAs) compete with Abeta oligomers for
      binding to domain 3, but the determinant of the HSA/Abeta oligomer interactions
      are markedly distinct from those of FAs. Although salt bridges with the FA
      carboxylate determine the FA binding affinities, hydrophobic contacts are pivotal
      for Abeta oligomer recognition. Specifically, we identified a site of Abeta
      oligomer recognition that spans the HSA (494-515) region and aligns with the
      central hydrophobic core of Abeta. The HSA (495-515) segment includes residues
      affected by FA binding and this segment is prone to self-associate into beta
      amyloids, suggesting that sites involved in fibrilization may provide a lead to
      develop inhibitors of Abeta self-association.

PMID- 24094412
TI  - Transmembrane current imaging in the heart during pacing and fibrillation.
AB  - Recently, we described a method to quantify the time course of total
      transmembrane current (Im) and the relative role of its two components, a
      capacitive current (Ic) and a resistive current (Iion), corresponding to the
      cardiac action potential during stable propagation. That approach involved
      recording high-fidelity (200 kHz) transmembrane potential (Vm) signals with glass
      microelectrodes at one site using a spatiotemporal coordinate transformation via
      measured conduction velocity. Here we extend our method to compute these
      transmembrane currents during stable and unstable propagation from fluorescence
      signals of Vm at thousands of sites (3 kHz), thereby introducing transmembrane
      current imaging. In contrast to commonly used linear Laplacians of extracellular
      potential (Ve) to compute Im, we utilized nonlinear image processing to compute
      the required second spatial derivatives of Vm. We quantified the dynamic spatial
      patterns of current density of Im and Iion for both depolarization and
      repolarization during pacing (including nonplanar patterns) by calibrating data
      with the microelectrode signals. Compared to planar propagation, we found that
      the magnitude of Iion was significantly reduced at sites of wave collision during
      depolarization but not repolarization. Finally, we present uncalibrated dynamic
      patterns of Im during ventricular fibrillation and show that Im at singularity
      sites was monophasic and positive with a significant nonzero charge (Im
      integrated over 10 ms) in contrast with nonsingularity sites. Our approach should
      greatly enhance the understanding of the relative roles of functional (e.g., rate
      dependent membrane dynamics and propagation patterns) and static spatial
      heterogeneities (e.g., spatial differences in tissue resistance) via recordings
      during normal and compromised propagation, including arrhythmias.

PMID- 24094413
TI  - Covalent modification cycles through the spatial prism.
AB  - Covalent modification cycles are basic units and building blocks of
      posttranslational modification and cellular signal transduction. We
      systematically explore different spatial aspects of signal transduction in
      covalent modification cycles by starting with a basic temporal cycle as a
      reference and focusing on steady-state signal transduction. We consider, in turn,
      the effect of diffusion on spatial signal transduction, spatial analogs of
      ultrasensitive behavior, and the interplay between enzyme localization and
      substrate diffusion. Our analysis reveals the need to explicitly account for
      kinetics and diffusional transport (and localization) of enzymes, substrates, and
      complexes. It demonstrates a complex and subtle interplay between spatial
      heterogeneity, diffusion, and localization. Overall, examining the spatial
      dimension of covalent modification reveals that 1), there are important
      differences between spatial and temporal signal transduction even in this cycle;
      and 2), spatial aspects may play a substantial role in affecting and distorting
      information transfer in modules/networks that are usually studied in purely
      temporal terms. This has important implications for the systematic understanding
      of signaling in covalent modification cycles, pathways, and networks in multiple
      cellular contexts.

PMID- 24094414
TI  - Concentrations and speciation of heavy metals in sludge from nine textile dyeing
      plants.
AB  - The safe disposal of sludge from textile dyeing industry requires research on
      bioavailability and concentration of heavy metals. In this study, concentrations
      and chemical speciation of heavy metals (Cd, Cr, Cu, Ni, Zn, Pb) in sludge from
      nine different textile dyeing plants were examined. Some physiochemical features
      of sludge from textile dyeing industry were determined, and a sequential
      extraction procedure recommended by the Community Bureau of Reference (BCR) was
      used to study the metal speciation. Cluster analysis (CA) and principal component
      analysis (PCA) were applied to provide additional information regarding
      differences in sludge composition. The results showed that Zn and Cu contents
      were the highest, followed by Ni, Cr, Cd and Pb. The concentration of Cd and Ni
      in some sludge samples exceeded the standard suggested for acidic soils in China
      (GB18918-2002). In sludge from textile dyeing plants, Pb, Cd and Cr were
      principally distributed in the oxidizable and residual fraction, Cu in the
      oxidizable fraction, Ni in all four fractions and Zn in the acid
      soluble/exchangeable and reducible fractions. The pH and heat-drying method
      affected the fractionation of heavy metals in sludge. 

PMID- 24094415
TI  - Optimization of recovery patterns in common carp exposed to roundup using
      response surface methodology: evaluation of neurotoxicity and genotoxicity
      effects and biochemical parameters.
AB  - The present study is the first report on optimization of recovery conditions of
      fishes exposed to pesticides using response surface methodology-central composite
      rotatable design (RSM-CCRD). The sub-lethal toxicity bioassay of Roundup(r) (2
      ppm ~10 percent LC50, 96 h) in common carp (1, 4, 9, 16, 25, 35 and 40 day) was
      investigated. After exposure for 16 days to Roundup(r), some the fishes were
      introduced to herbicide-free water. The effects of four recovery parameters
      including time (5-25 d), temperature (18-26  degrees C), water exchange rate
      (WER, 10-30), and salinity (0-8 ppt) on the levels of biomarkers of genotoxicity
      (DNA damage), neurotoxicity (acetylcholinesterase activity (AChE)), and the serum
      alanine (ALT) and aspartate (AST) aminotransferase in plasma were studied. The
      polynomial equations were significantly fitted for all response variables with
      high R2 values (>0.95), which revealed no indication of lack of fit. The optimum
      conditions for the maximum AChE activity (37.14 nmol/min/mg protein) and the
      minimum levels of DNA damage (8.00 percent tail DNA), ALT (27.0 IU/L) and AST
      (91.0 IU/L) were time of 20 d, temperature of 20  degrees C, WER of 25 and water
      salinity of 6 ppt. Thus, a promising improvement for the recovery trend of fishes
      exposed to Roundup(r) stress was obtained under the optimized conditions using
      RSM-CCRD.

PMID- 24094416
TI  - Probiotic modulation of dendritic cell function is influenced by ageing.
AB  - Dendritic cells (DCs) are critical for the generation of T-cell responses. DC
      function may be modulated by probiotics, which confer health benefits in
      immunocompromised individuals, such as the elderly. This study investigated the
      effects of four probiotics, Bifidobacterium longum bv. infantis CCUG 52486, B.
      longum SP 07/3, Lactobacillus rhamnosus GG (L.GG) and L. casei Shirota (LcS), on
      DC function in an allogeneic mixed leucocyte reaction (MLR) model, using DCs and
      T-cells from young and older donors in different combinations. All four
      probiotics enhanced expression of CD40, CD80 and CCR7 on both young and older
      DCs, but enhanced cytokine production (TGF-beta, TNF-alpha) by old DCs only. LcS
      induced IL-12 and IFNgamma production by DC to a greater degree than other
      strains, while B. longum bv. infantis CCUG 52486 favoured IL-10 production.
      Stimulation of young T cells in an allogeneic MLR with DC was enhanced by
      probiotic pretreatment of old DCs, which demonstrated greater activation (CD25)
      than untreated controls. However, pretreatment of young or old DCs with LPS or
      probiotics failed to enhance the proliferation of T-cells derived from older
      donors. In conclusion, this study demonstrates that ageing increases the
      responsiveness of DCs to probiotics, but this is not sufficient to overcome the
      impact of immunosenescence in the MLR. 

PMID- 24094417
TI  - Long term human reconstitution and immune aging in NOD-Rag (-)-gamma chain (-)
      mice.
AB  - Aging of the human immune system is characterized by a gradual loss of immune
      function and a skewing of hematopoiesis toward the myeloid lineage, a reduction
      in the lymphocytic lineage, and progressive increases in senescent memory T cells
      at the expense of naive T cells. Both the innate and the adaptive branches of the
      immune system are affected, including neutrophils, macrophages, dendritic cells
      and lymphocytes. Mice, the most common research model, although inexpensive, do
      not necessarily reflect the human immune system in terms of its interaction with
      infectious agents of human origin or environmental factors. This study analyzed
      whether a human immune system contained within the NOD-Rag (-)-gamma chain (-)
      mouse model could realistically be used to evaluate the development and therapy
      of aging-related diseases. To that end lightly irradiated NOD-Rag (-)-gamma chain
      (-) mice were injected intra-hepatically on day 1 of life with purified cord
      blood-derived CD34(+) stem and progenitor cells. Multiple mice were constructed
      from each cord blood donor. Mice were analyzed quarterly for age-related changes
      in the hematopoietic and immune systems, and followed for periods up to 18-24
      months post-transplant. Flow cytometric analyses were performed for hematopoietic
      and immune reconstitution. It was observed that NOD-Rag (-)-gamma chain (-) mice
      could be "humanized" long-term using cord blood stem cells, and that some
      evidence of immune aging occurred during the life of the mice. 

PMID- 24094418
TI  - Changing trends in symptomatology, diagnostics, stage and survival of prostate
      cancer in Northern Finland during a period of 20 years.
AB  - BACKGROUND: Prostate cancer is the most common cancer among men in many
      countries. The aim of the present study was to find out how the symptoms leading
      to a diagnosis, diagnostic procedures and stages of the disease among prostate
      cancer patients have changed over a period of 20 years. METHODS: This
      retrospective chart review consisted of 421 prostate cancer patients whose
      treatment was started in the years 1982, 1987, 1992, 1997 and 2002 at the Oulu
      University Hospital. Earlier prostatic disorders, specific urological symptoms,
      diagnostic procedures, the TNM classification and histological grade were
      recorded. RESULTS: The number of symptom-free prostate cancer patients increased
      over the 20 years, as did the number of men suffering from chronic prostatitis,
      although the latter increase was not statistically significant. A drop in the
      number of clinical T4 cases and increase of clinical T1 and clinical T2 cases was
      recorded but no clear change in the histological distribution occurred. The 5
      year prostate cancer-specific survival improved significantly over the 20 years.
      The urologist was found to be the person who was contacted first most often.
      CONCLUSIONS: Our data indicate that the number of prostate cancer patients has
      increased hugely over the period from 1982 to 2002 and although the clinical T
      stage has moved towards earlier stages, the proportion of well differentiated
      cancers remains low, so that most patients have clinically significant cancer
      with the need of some form of therapy. Further, prostate cancer-specific survival
      improved significantly over the period.

PMID- 24094419
TI  - Relationships among the cervical mucus urea and acetone, accuracy of insemination
      timing, and sperm survival in Holstein cows.
AB  - The objectives of this study were to evaluate the relationships among urea and
      acetone content in cows' cervical mucus (CM), its crystallization type (CT) and
      sperm survival (SS) after timed AI. Samples of CM were collected from 192
      Holstein cows treated by Ovsynch((r)) protocol. Analysis of the urea and acetone
      content for identification of the metabolic status, the arborization test for
      evaluation of insemination timing and the short-term heat test of SS for
      assessment of its suitability as a biological matrix were performed. The data set
      was analyzed by the GLM procedure using SAS((r)). The results documented the
      existence of substantial differences in individual response to the Ovsynch((r))
      protocol causing insemination of 55.2% cows at an inappropriate time. The urea
      content was found as a possible indicator of a cow's metabolism and/or of
      insemination timing, concentrations of less than 500 mg/L corresponded (P<0.05
      0.01) to the cows' expected response to timed AI. The greater the urea content,
      the greater the proportion of cows inseminated at an inappropriate time. Effects
      (P<0.05-0.01) of CT, urea and acetone content on SS were determined. The greatest
      values of SS were detected in cows with an expected response to precisely timed
      oestrus documented by the corresponding CT. Greater values of urea (>260 mg/L)
      and acetone (>5mg/L) negatively affected SS as well (P<0.05-0.01). The results
      confirmed that the accuracy of insemination timing can be affected by the
      metabolism intensity, just as CM quality directly influences sperm survival.

PMID- 24094420
TI  - Access to fertility treatment by gays, lesbians, and unmarried persons: a
      committee opinion.
AB  - This statement explores the implications of reproduction by single individuals,
      unmarried heterosexual couples, and gay and lesbian couples, and concludes that
      ethical arguments supporting denial of access to fertility services on the basis
      of marital status or sexual orientation cannot be justified. This document
      replaces the previous version of this document by the same name, published in
      November 2006 (Fertil Steril 2009;92:1190-3).

PMID- 24094421
TI  - Effects of mifepristone on uterine leiomyoma in premenopausal women: a meta
      analysis.
AB  - OBJECTIVE: To conduct a meta-analysis of the studies assessing the effects of
      mifepristone on the uterus, uterine leiomyoma, and leiomyoma-related symptoms in
      premenopausal women. DESIGN: Meta-analysis. SETTING: Centers for reproductive
      care. PATIENT(S): Premenopausal women who suffered from leiomyoma.
      INTERVENTION(S): We identified all of the studies published before December 2012
      that compared the status of patients with leiomyoma before and after treatment
      with mifepristone. MAIN OUTCOME MEASURE(S): Leiomyoma-related symptoms, uterine
      or leiomyoma volume, changes in endometrial thickness. RESULT(S): A meta-analytic
      technique was used to study 11 randomized controlled trials involving 780 women
      with symptomatic uterine leiomyomas. The subjects received 2.5-25 mg/d of
      mifepristone for 3-6 months. Mifepristone could effectively reduce uterine and
      leiomyoma volume and alleviate leiomyoma symptoms, including hypermenorrhea, the
      mean menstrual blood loss, pelvic pain, pelvic pressure, anemia, and
      dysmenorrhea. There was no significant difference in the rate of atypical
      endometrial hyperplasia between the mifepristone treatment group and the placebo
      group. CONCLUSION(S): Mifepristone significantly reduced uterine and leiomyoma
      volume and alleviated leiomyoma-related symptoms. We recommend 2.5 mg of
      mifepristone administered daily for 3 or 6 months as the optimum clinical
      treatment for leiomyoma. There is insufficient evidence that mifepristone
      treatment led to atypical endometrial hyperplasia.

PMID- 24094422
TI  - Testosterone use in the male infertility population: prescribing patterns and
      effects on semen and hormonal parameters.
AB  - OBJECTIVE: To analyze how frequently and why men presenting with infertility take
      testosterone (T) and if negative effects of T on semen parameters are reversed
      following cessation. DESIGN: Analysis of a prospectively collected database.
      SETTING: Male Infertility clinic. PATIENT(S): Men presenting for fertility
      evaluation from 2008 to 2012. INTERVENTION(S): None. MAIN OUTCOME MEASURE(S): The
      frequency and reason for T use in the infertile male population, and semen and
      hormonal parameters while on T and following discontinuation. RESULT(S): A total
      of 59/4,400 men (1.3%) reported taking T. T was prescribed by a variety of
      physicians, including endocrinologists (24%), general practitioners (17%),
      urologists (15%), gynecologists (5%), and reproductive endocrinologists (3%).
      Only one of the men admitted that he had obtained T from an illicit source. More
      than 82% of men were prescribed T for the treatment of hypogonadism, but
      surprisingly, 12% (7/59) were prescribed T to treat their infertility. While on
      T, 88.4% of men were azoospermic, but by 6 months after T cessation, 65% of the
      men without other known causes for azoospermia recovered spermatogenesis.
      CONCLUSION(S): In Canada, T was not commonly used by men presenting for fertility
      investigation (1.3%). Close to 2/3 of infertile men using T recovered
      spermatogenesis within 6 months of T discontinuation.

PMID- 24094423
TI  - Fertility preservation and reproduction in patients facing gonadotoxic therapies:
      a committee opinion.
AB  - Chemotherapy and radiation therapy often result in reduced fertility, and
      patients receiving gonadotoxic treatment should be informed of options for
      fertility preservation and future reproduction prior to such treatment.
      Reproduction in the context of cancer also raises a number of ethical issues
      related to the welfare of both patients and offspring. This document replaces the
      document titled, "Fertility preservation and reproduction in cancer patients,"
      last published in 2005 (Fertil Steril 2005;83:1622-8). 

PMID- 24094424
TI  - Semen quality in relation to antioxidant intake in a healthy male population.
AB  - OBJECTIVE: To assess the relationship between dietary antioxidant intake and
      semen quality in young healthy males. DESIGN: Cross-sectional study. SETTING:
      University and college campuses in the Rochester, New York, area. PATIENT(S): One
      hundred eighty-nine university-aged men. INTERVENTION(S): None. MAIN OUTCOME
      MEASURE(S): Semen volume, total sperm count, concentration, motility, total
      motile count, and morphology. RESULT(S): Progressive motility was 6.5 (95%
      confidence interval [CI], 0.6, 12.3) percentage units higher among men in the
      highest quartile of beta-carotene intake compared with men in the lowest
      quartile. Similar results were observed for lutein intake. Lycopene intake was
      positively related to sperm morphology. The adjusted percentages (95% CI) of
      morphologically normal sperm in increasing quartiles of lycopene intake were 8.0
      (6.7, 9.3), 7.7 (6.4, 9.0), 9.2 (7.9, 10.5), and 9.7 (8.4, 11.0). There was a
      nonlinear relationship between vitamin C intake and sperm concentration, with men
      in the second quartile of intake having, on average, the highest sperm
      concentrations and men in the top quartile of intake having the lowest
      concentrations. CONCLUSION(S): In a population of healthy young men, carotenoid
      intake was associated with higher sperm motility and, in the case of lycopene,
      better sperm morphology. Our data suggest that dietary carotenoids may have a
      positive impact on semen quality.

PMID- 24094425
TI  - Transcultural adaptation to Spanish of the instrument "Effectiveness of Auditory
      Rehabilitation" for the assessment of quality of life in patients using hearing
      aids.
AB  - INTRODUCTION AND OBJECTIVES: It is becoming increasingly important to have
      reliable and valid questionnaires. This becomes especially important when
      evaluating hearing loss. THE AIM OF THIS WORK WAS TO VALIDATE: the "Effectiveness
      of Auditory Rehabilitation" (EAR) questionnaire for the Spanish-speaking
      population. This instrument assesses quality of life and hearing aspects in
      patients using hearing aids. MATERIAL AND METHOD: Cross-sectional validation
      study. A cultural adaptation through the use of English to Spanish translations
      and re-translations was carried out. The validity and reliability of the newly
      adapted instrument were evaluated. RESULTS: A total of 69 individuals (44 older
      adults and 25 younger adults) were examined. The pure-tone averages (PTA, 500,
      1,000 and 2,000 Hz) were 47.3 dB HL and 47.1 dB HL for the left and right ears,
      respectively. The mean maximum speech discrimination in silence for monosyllables
      were 83.3% and 82.9% for the left and right ears, respectively. Internal
      consistency presented Cronbach alpha values of 0.85 and 0.77 for the internal and
      external dimensions, respectively. The intraclass correlation coefficients were
      0.80 for the internal module and 0.85 for the external module. Construct validity
      reported a correlation coefficient of 0.71 at baseline and 0.76 at 3 months after
      the initial assessment for the internal module, and 0.62 at baseline and 0.74 at
      3 months after the initial assessment for the external module. The size effects
      were 1.3 and 1.1 for the internal and external modules, respectively. DISCUSSION:
      The Spanish version of the EAR questionnaire seems to be a reliable and valid
      instrument. The evaluation of audiological aspects, as well as aspects relating
      to aesthetics and comfort are the main strengths of this instrument. Finally, the
      EAR scale is more sensitive to change than other scales.

PMID- 24094426
TI  - Cerebellopontine angle epidermoid cyst.

PMID- 24094427
TI  - Black cervical lymphadenopathies.

PMID- 24094428
TI  - [Otorhinolaryngological manifestations in patients with Behcet disease].
AB  - INTRODUCTION AND OBJECTIVES: Behcet disease (BD) is a systemic immune-mediated
      vasculitis of unknown origin characterised by recurrent orogenital ulceration,
      ocular inflammation and skin lesions. The aim of our study was to identify ear,
      nose and throat (ENT) manifestations associated with BD. PATIENTS AND METHODS:
      Retrospective review of the medical records of all patients diagnosed with BD who
      attended a tertiary public hospital in Cantabria (Spain) over a period of 22
      years. Clinical manifestations, in particular those concerning ENT, were
      retrieved from medical records. A medical literature review of ENT manifestations
      was conducted. RESULTS: Thirty-three patients (age range: 17-64 years) were
      included in the study. Most of them presented oral ulcers (97%). Eight patients
      (24%) presented oropharyngeal ulcers and 5 patients (15%) experienced
      audiovestibular symptoms (high frequency sensorineural hearing loss, vertigo and
      bilateral vestibular hypofunction). One patient had symptoms compatible with
      vestibular neuronitis as the presentation manifestation of Neuro-Behcet. In 4
      patients (12%) the presence of odynophagia secondary to the presence of
      oropharyngeal lesions, initially interpreted as acute or recurrent tonsillitis,
      was the first manifestation of the disease, alone or associated with cutaneous or
      ocular lesions. CONCLUSIONS: In addition to the characteristic oral ulcers
      present in most patients with BD, ulcers in the oropharynx, occasionally
      interpreted as acute pharyngitis, are also common in these patients.
      Audiovestibular manifestations frequently appear during the course of the disease
      and may be the first symptom of central nervous system involvement.

PMID- 24094429
TI  - Septic arthritis of the acromioclavicular joint: an uncommon location.
AB  - Septic pyogenic arthritis of the acromioclavicular joint is a rare entity that
      occurs in immunosuppressed patients or those with discontinuity of defense
      barriers. There are only 15 cases described in the literature. The diagnosis is
      based on clinical features and the isolation of a microorganism in synovial fluid
      or blood cultures. The evidence of arthritis by imaging (MRI, ultrasound or
      scintigraphy) may be useful. Antibiotic treatment is the same as in septic
      arthritis in other locations. Staphylococcus aureus is the microorganism most
      frequently isolated. Our objective was to describe the clinical features,
      treatment and outcome of patients diagnosed with septic arthritis of the
      acromioclavicular joint at a Rheumatology Department. We developed a study with a
      retrospective design (1989-2012). The medical records of patients with septic
      arthritis were reviewed (101 patients). Those involving the acromioclavicular
      joint were selected (6 patients; 6%). 

PMID- 24094430
TI  - Central nervous system infection by Listeria monocytogenes in patients with
      systemic lupus erythematosus: analysis of 26 cases, including the report of a new
      case.
AB  - INTRODUCTION: Infections in patients with systemic lupus erythematosus cause
      significant morbidity. Infection due to Listeria monocytogenes (LM) is considered
      an opportunistic disease, and has been published on rare occasions in patients
      with SLE. OBJECTIVE: To review the presentation of listeria infections in the
      central nervous system (CNS) in SLE patients. METHODOLOGY: We conducted a
      literature review, selecting cases with central nervous system infection and
      confirmation of LM infection through culture. RESULTS: Twenty six cases are
      described. The most common presentation was meningitis, with meningoencephalitis
      and brain abscesses being less frequent. The predisposing factors are: use of
      glucocorticoids, immunosuppressants, renal replacement therapy and the activity
      flares. CONCLUSION: CNS infection by listeria is rare and sometimes fatal. The
      atypical presentation may lead to a delay in diagnosis and appropriate treatment.
      L. monocytogenes should be included in the differential diagnosis of patients
      with SLE with neurological manifestations.

PMID- 24094431
TI  - Iron deficiency in patients with idiopathic pulmonary arterial hypertension.
AB  - BACKGROUND: Iron deficiency has been reported to be highly prevalent in
      idiopathic pulmonary arterial hypertension (iPAH) patients, with the potential to
      influence cardiac performance, pulmonary artery pressures and the pulmonary
      vascular response to hypoxia. METHODS: Iron status was evaluated in 29 iPAH
      patients, and was related to haemodynamic, echocardiographic and exercise
      parameters. RESULTS: Iron deficiency was present in 44.8% of all iPAH patients,
      although anaemia was only present in 13.8%. Iron-deficient patients had similar
      exercise capacity (6MWD: 446+/-141 m), compared to iron-sufficient patients
      (421+/-193 m), however 46.2% of iron deficient patients had NYHA FC 3 or higher,
      compared to 12.5% in non-iron deficient group. Additionally iron-deficient
      patients showed increased mean pulmonary arterial pressure (63.3+/-12.2 mmHg;
      iron deficient vs. 38.8+/-16.7 mmHg; non-iron deficient) and reduced cardiac
      index (1.3+/-0.2 L/min/m(2); iron deficient vs. 2.5+/-0.4 L/min/m(2); non-iron
      deficient). CONCLUSIONS: Iron deficiency is highly prevalent in iPAH, and the
      extent of iron deficiency is related to haemodynamics and NYHA functional class.
      While the exact mechanism of iron deficiency is unknown, our study suggests that
      treatment of iron deficiency should be considered in iPAH patients.

PMID- 24094432
TI  - Discovery of 2-aryl-8-hydroxy (or methoxy)-isoquinolin-1(2H)-ones as novel EGFR
      inhibitor by scaffold hopping.
AB  - 2-Aryl-8-hydroxy (or methoxy)-isoquinolin-1(2H)-one has been proposed as a novel
      scaffold of EGFR inhibitor based on scaffold hoping. In the present study, a
      series of 2-aryl-8-hydroxy (or methoxy)-isoquinolin-1(2H)-one derivatives were
      synthesized. Their antiproliferative activities in vitro were evaluated via MTT
      assay against two human cancer cell lines, including A431 and A549. The SAR of
      the title compounds was preliminarily discussed. The compounds with ideal
      inhibition were evaluated through ELISA-based EGFR-TK assay. Compound 6c showed
      the best activity against A431 and EGFR tyrosine kinase. These findings suggest
      that title compounds are EGFR inhibitors with novel structures. 

PMID- 24094433
TI  - Design, synthesis and antiproliferative evaluation of fluorenone analogs with DNA
      topoisomerase I inhibitory properties.
AB  - A series of 2,7-diamidofluorenones were designed, synthesized, and screened by
      SRB assay. Some synthesized compounds exhibited antitumor activities in
      submicromolar range. Ten compounds (3a, 3b, 3c, 3g, 3j, 3l, 4a, 4h, 4i, and 4j)
      were also selected by NCI screening system and 3c (GI50=1.66 MUM) appeared to be
      the most active agent of this series. Furthermore, 3c attenuated topoisomerase I
      mediated DNA relaxation at low micromolar concentrations. These results indicated
      that fluorenones have potential to be further developed into anticancer drugs.

PMID- 24094434
TI  - Spectroscopic identification and anti-biofilm properties of polar metabolites
      from the medicinal plant Helichrysum italicum against Pseudomonas aeruginosa.
AB  - Two new acylated styrylpyrones, one 5-methoxy-1(3H)-isobenzofuranone glucoside
      and a hydroxymethyl-orcinol derivative, along with sixteen known aromatic
      metabolites, including lignans, quinic acid derivatives low-molecular weight
      phenol glucosides, have been isolated from the methanol extract of Helichrysum
      italicum, a medicinal plant typical of the Mediterranean vegetation. The
      structures of these compounds have been elucidated on the basis of extensive 2D
      NMR spectroscopic analyses, including COSY, TOCSY, HSQC, CIGAR-HMBC, H2BC and
      HSQC-TOCSY, along with Q-TOF HRMS(2) analysis. Selected compounds were evaluated
      for their anti-biofilm properties against Pseudomonas aeruginosa. 

PMID- 24094435
TI  - Antibody-catalyzed decarboxylation and aldol reactions using a primary amine
      molecule as a functionalized small nonprotein component.
AB  - Catalytic antibody 27C1 bears binding sites for both a substrate- and a
      functionalized small nonprotein component in the active site. We investigated the
      possibility of exploiting imine and enamine intermediates using a primary amine
      molecule into the active site of antibody 27C1. The antibody catalyzed beta-keto
      acid decarboxylation with a rate enhancement (kcat/Km/kuncat) of 140,000, as well
      as highly regioselective cross-aldol reactions of ketones and p
      nitrobenzaldehyde. These studies provide new strategies for the generation of
      catalytic antibodies possessing binding sites for functionalized components. 

PMID- 24094436
TI  - Synthesis and biological evaluation of 5-carbamoyl-2-phenylpyrimidine derivatives
      as novel and potent PDE4 inhibitors.
AB  - 5-Carbamoyl-2-phenylpyrimidine derivative 2 has been identified as a
      phosphodiesterase 4 (PDE4) inhibitor with moderate PDE4B inhibitory activity
      (IC50=200 nM). Modification of the carboxylic acid moiety of 2 gave N
      neopentylacetamide derivative 10f, which had high in vitro PDE4B inhibitory
      activity (IC50=8.3 nM) and in vivo efficacy against lipopolysaccharide (LPS)
      induced pulmonary neutrophilia in mice (ID50=16 mg/kg, ip). Furthermore, based on
      the X-ray crystallography of 10f bound to the human PDE4B catalytic domain, we
      designed 7,8-dihydro-6H-pyrido[4,3-d]pyrimidin-5-one derivative 39 which has a
      fused bicyclic lactam scaffold. Compound 39 exhibited excellent inhibitory
      activity against LPS-induced tumor necrosis factor alpha (TNF-alpha) production
      in mouse splenocytes (IC50=0.21 nM) and in vivo anti-inflammatory activity
      against LPS-induced pulmonary neutrophilia in mice (41% inhibition at a dose of
      1.0 mg/kg, i.t.).

PMID- 24094437
TI  - A PEGylated analog of the gut hormone oxyntomodulin with long-lasting
      antihyperglycemic, insulinotropic and anorexigenic activity.
AB  - Peptide agonists of the glucagon-like peptide 1 (GLP-1) receptor (GLP1R) are
      rapidly gaining favor as antidiabetic agents, since in addition to increasing
      glucose-dependent insulin secretion, they also cause weight loss. Oxyntomodulin
      (OXM), a natural peptide with sequence homology to both glucagon and GLP-1, has
      glucose-lowering activity in rodents and anorectic activity in rodents and
      humans, but its clinical utility is limited by a short circulatory half-life due
      to rapid renal clearance and degradation by dipeptidyl peptidase IV (DPP-IV).
      Here, we describe the development of a novel DPP-IV-resistant, long-acting GLP1R
      agonist, based on derivatization of a suitably chosen OXM analog with high
      molecular weight polyethylene glycol (PEG) ('PEGylation'). PEG-OXM exerts an anti
      hyperglycemic effect in diet-induced obese (DIO) mice in a glucose-dependent
      manner, with a maximally efficacious dose of 0.1mg/kg, and reduces food intake
      and body weight with a minimally efficacious dose of 1mg/kg. If this pharmacology
      is recapitulated in patients with type 2 diabetes, these results indicate PEG-OXM
      as a potential novel once-weekly GLP-1 mimetic with both glucose-lowering
      activity and weight loss efficacy. 

PMID- 24094438
TI  - How do hospitals cope with sustained slow growth in Medicare prices?
AB  - OBJECTIVE: To estimate the effects of changes in Medicare inpatient hospital
      prices on hospitals' overall revenues, operating expenses, profits, assets, and
      staffing. PRIMARY DATA SOURCE: Medicare hospital cost reports (1996-2009). STUDY
      DESIGN: For each hospital, we quantify the year-to-year price impacts from
      changes in the Medicare payment formula. We use cumulative simulated price
      impacts as instruments for Medicare inpatient revenues. We use a series of two
      stage least squares panel data regressions to estimate the effects of changes in
      Medicare revenues among all hospitals, and separately among not-for-profit versus
      for-profit hospitals, and among hospitals experiencing real price increases
      ("gainers") versus decreases ("losers"). PRINCIPAL FINDINGS: Medicare price cuts
      are associated with reductions in overall revenues even larger than the direct
      Medicare price effect, consistent with price spillovers. Among not-for-profit
      hospitals, revenue reductions are fully offset by reductions in operating
      expenses, and profits are unchanged. Among for-profit hospitals, revenue
      reductions decrease profits one-for-one. Responses of gainers and losers are
      roughly symmetrical. CONCLUSIONS: On average, hospitals do not appear to make up
      for Medicare cuts by "cost shifting," but by adjusting their operating expenses
      over the long run. The Medicare price cuts in the Affordable Care Act will "bend
      the curve," that is, significantly slow the growth in hospitals' total revenues
      and operating expenses.

PMID- 24094439
TI  - Perioperative fibrinolysis and duration of antifibrinolytic treatment.

PMID- 24094440
TI  - [Learn first, then teach].

PMID- 24094441
TI  - [Reproducibility and accuracy in the morphometric and mechanical quantification
      of trabecular bone from 3 Tesla magnetic resonance images].
AB  - OBJECTIVE: We used an animal model to analyze the reproducibility and accuracy of
      certain biomarkers of bone image quality in comparison to a gold standard of
      computed microtomography (MUCT). MATERIAL AND METHODS: We used magnetic resonance
      (MR) imaging and MUCT to study the metaphyses of 5 sheep tibiae. The MR images (3
      Teslas) were acquired with a T1-weighted gradient echo sequence and an isotropic
      spatial resolution of 180MUm. The MUCT images were acquired using a scanner with
      a spatial resolution of 7.5MUm isotropic voxels. In the preparation of the
      images, we applied equalization, interpolation, and thresholding algorithms. In
      the quantitative analysis, we calculated the percentage of bone volume (BV/TV),
      the trabecular thickness (Tb.Th), the trabecular separation (Tb.Sp), the
      trabecular index (Tb.N), the 2D fractal dimension (D(2D)), the 3D fractal
      dimension (D(3D)), and the elastic module in the three spatial directions (Ex, Ey
      and Ez). RESULTS: The morphometric and mechanical quantification of trabecular
      bone by MR was very reproducible, with percentages of variation below 9% for all
      the parameters. Its accuracy compared to the gold standard (MUCT) was high, with
      errors less than 15% for BV/TV, D(2D), D(3D), and E(app)x, E(app)y and E(app)z.
      CONCLUSIONS: Our experimental results in animals confirm that the parameters of
      BV/TV, D(2D), D(3D), and E(app)x, E(app)y and E(app)z obtained by MR have
      excellent reproducibility and accuracy and can be used as imaging biomarkers for
      the quality of trabecular bone.

PMID- 24094442
TI  - [Population-based breast cancer screening: certainties, controversies, and future
      perspectives].
AB  - Population-based breast cancer screening programs based on mammography must
      maintain a high level of quality, so the results must be constantly monitored.
      Although most authors consider that these programs have decreased the mortality
      due to breast cancer by about 30%, others claim that the mortality has decreased
      by only about 12% due to errors in the randomization of patients, because the
      rate of advanced tumors has hardly decreased and because adjuvant treatment also
      improves survival. Other criticisms focus on overdiagnosis and overtreatment. We
      believe that despite the unquestionable value of mammographic screening, we
      should be open to certain changes such as the stratification of patients by their
      level of risk and the introduction of complementary techniques like
      tomosynthesis, ultrasonography, and magnetic resonance imaging in selected cases.

PMID- 24094443
TI  - Relationship between skin prick and atopic patch test reactivity to aeroallergens
      and disease severity in children with atopic dermatitis.
AB  - BACKGROUND: The immunological mechanism in aetiology of atopic dermatitis (AD)
      shows significant differences from other allergic diseases. Allergen inhalation
      exacerbates AD lesions and AD patients' complaints decrease in house dust mite
      (HDM) low level environments, which reveals the importance of inhalant allergens.
      OBJECTIVE: We evaluated the skin prick test (SPT) and atopy patch test (APT)
      positivity rates with aeroallergens and studied the effect of test results, and
      aimed to determine the value of allergic test reactivity on the clinical
      characteristics of children with AD. METHODS: Forty-five children aged 2-15 years
      with AD were included to study between May 2006 and May 2007 in GATA Haydarpasa
      Teaching Hospital, Allergy Department. The reactivity to inhalant allergens using
      SPT and APT was evaluated. The severity of AD, which was assessed with SCORAD,
      was compared with aeroallergen hypersensitivity. RESULTS: The highest positivity
      of APT was seen against HDM (48.9%). HDM SPT positivity and subjective symptoms
      score were statistically correlated (P<0.05). Patients with strong SPT positivity
      to HDM had a higher total SCORAD score (P<0.05). Although there was no
      statistical correlation between HDM APT and SCORAD parameters, APT positive
      patients had generally higher SCORAD parameters. The statistical significance was
      only shown between the extent of the disease and strong APT positive reactions to
      Dermatophagoides pteronyssinus. CONCLUSION: HDM allergens play an important role
      in determining the clinical severity of AD and strong APT positivity could be
      more meaningful clinically.

PMID- 24094444
TI  - Factors affecting quality of life of asthma patients in Spain: the importance of
      patient education.
AB  - OBJECTIVES: Assessment of demographic and clinical factors that have an impact on
      the quality of life (QoL) of patients with asthma in Spain. PATIENTS AND METHODS:
      Multicenter, prospective, observational, cohort study, conducted in 40 Spanish
      Pneumology Units during a 12-month period. Data on sociodemographic, clinical
      variables, asthma treatment and QoL were collected in a case report form.
      RESULTS: 536 patients (64.6% women, mean age: 54) were recruited. Reported QoL
      was better for patients from Northern and Central Spain as compared with those
      from the South and the East (p<0.001), students and employed patients as compared
      with housewives and unemployed (p<0.01), for those who had received asthma
      information (p<0.01), for those with milder daytime symptoms (p<0.01) and for
      patients with higher level of education (p<0.05). CONCLUSIONS: Among the factors
      that have a significant effect on patients' QoL only symptom control and patient
      education on asthma control are modifiable. Therefore, all the strategies should
      be tailored to improve such factors when managing asthma patients.

PMID- 24094445
TI  - Assay of IL-22 and IL-25 in serum, whole blood, and peripheral blood mononuclear
      cell cultures of patients with severe asthma.
AB  - BACKGROUND: Although some studies show that IL-22 and IL-25 play critical roles
      in the pathogenesis of asthma, little is known about the systemic production of
      these cytokines. The aim of this study was to assay IL-22 and IL-25 in serum, in
      mitogen-activated whole blood (WB), and in mitogen-activated peripheral blood
      mononuclear cell (PBMC) cultures of patients with severe asthma. METHODS: In this
      cross-sectional study, a questionnaire was prepared to determine the severity of
      asthma. Through the questionnaire, information including clinical signs, clinical
      symptoms, and past medical history were acquired. Information collected allowed
      all patients who were active or ex-smokers to be excluded. A trained observer
      assessed airway reversibility, peak flowmetry, and spirometry in the remaining
      patients. Twenty-one patients and simultaneously, twenty age- and sex-matched
      healthy controls were selected. Sterile blood (10ml) was taken from each study
      participant. Sera were isolated and anticoagulant blood used for WB and PBMC
      cultures and haematological tests. Phytohaemagglutinin and lipopolysaccharide
      (LPS) were used to activate WB and PBMC. The data from these two groups were
      compared using Student's t-test. RESULTS: Although the total white blood cell
      count was elevated in the asthmatic group, other haematological indices,
      including IL-22 and IL-25 levels in the asthmatic group were not significantly
      (p>0.05) different from controls. CONCLUSIONS: The levels of IL-22 and IL-25 in
      patients with severe asthma are no higher than those of non-asthmatic
      individuals. Any major role for IL-22 and IL-25 in severe asthma is likely to be
      localised to the lungs and bronchial tissues.

PMID- 24094446
TI  - Stroke education program of act FAST for junior high school students and their
      parents.
AB  - BACKGROUND: We produced a stroke education program using the FAST (facial droop,
      arm weakness, speech disturbance, time to call an ambulance) mnemonic. AIMS: The
      aim of this study is to examine efficacy of our education program for junior high
      school students and their parents. METHODS: One hundred ninety students of 3
      junior high schools (aged 12-13 years) and their parents were enrolled. Students
      received a 45-minute lesson of stroke enlightenment using the FAST mnemonic.
      Enlightenment items, such as a magnet poster, were distributed. Parents were
      educated indirectly from their child. Surveys of stroke knowledge were examined
      at baseline, immediately after the lesson, and at 3 months after the lesson.
      RESULTS: For the students, correct answers at 3 months were significantly higher
      than those at baseline in questions of facial palsy (98% versus 33%), speech
      disturbance (98% versus 54%), numbness on one side (64% versus 42%), weakness on
      one side (80% versus 51%), calling an ambulance (88% versus 60%), alcohol
      drinking (85% versus 65%), smoking (70% versus 43%), dyslipidemia (58% versus
      46%), hyperglycemia (59% versus 48%), and obesity (47% versus 23%). At 3 months,
      the parents answered more correctly questions of facial palsy (93% versus 66%),
      calling an ambulance (95% versus 88%), and alcohol drinking (65% versus 51%) than
      at baseline. At 3 months, 96% of students and 78% of parents answered the FAST
      mnemonic correctly. CONCLUSIONS: Our stroke education program improved stroke
      knowledge, especially the FAST message, for junior high school students and their
      parents.

PMID- 24094447
TI  - [Drug-induced sleep videoendoscopy: clinical usefulness and literature review].
AB  - Fiberoptic examination of the pharynx under drug-induced sleep is a test that
      helps to detect the areas of vibration and collapse in patients with sleep
      disordered breathing. This article is a review of the available literature on the
      subject, aimed at helping otolaryngologists to understand the procedure and to
      resolve some controversies surrounding it.

PMID- 24094448
TI  - Increases in thyroid nodule fine-needle aspirations, operations, and diagnoses of
      thyroid cancer in the United States.
AB  - BACKGROUND: To provide population-based estimates of trends in thyroid nodule
      fine-needle aspirations (FNA) and operative volumes, we used multiple claims
      databases to quantify rates of these procedures and their association with the
      increasing incidence of thyroid cancer in the United States. METHOD: Private and
      public insurance claims databases were used to estimate procedure volumes from
      2006 to 2011. Rates of FNA and thyroid operations related to thyroid nodules were
      defined by CPT4 codes associated with International Classification of Diseases,
      Ninth Revision Clinical Modification codes for nontoxic uni- or multinodular
      goiter and thyroid neoplasms. RESULTS: Use of thyroid FNA more than doubled
      during the 5-year study period (16% annual growth). The number of thyroid
      operations performed for thyroid nodules increased by 31%. Total thyroidectomies
      increased by 12% per year, whereas lobectomies increased only 1% per year. In
      2011, total thyroidectomies accounted for more than half (56%) of the operations
      for thyroid neoplasms in the United States. Thyroid operations became
      increasingly (62%) outpatient procedures. CONCLUSION: Thyroid FNA and operative
      procedures have increased rapidly in the United States, with an associated
      increase in the incidence of thyroid cancer. The more substantial increase in
      number of total versus partial thyroid resections suggests that patients
      undergoing thyroid operation are perceived to have a greater risk of cancer as
      determined by preoperative assessments, but this trend could also increase
      detection of incidental microcarcinomas.

PMID- 24094450
TI  - The theory of compromised eating behavior.
AB  - The purpose of this inquiry was to develop substantive theory that describes the
      social process that influences the eating behavior of hospitalized older adults.
      Undernutrition contributes to negative health outcomes, such as increased
      morbidity and mortality in hospitalized older adults. Despite the availability of
      vast nutritional resources within the hospital environment, hospitalized older
      adults often have inadequate dietary intake. A grounded theory methodology was
      used to explore this phenomenon. The Theory of Compromised Eating Behavior
      describes the process of compromise that older adults experience related to
      eating behavior while hospitalized. The theory has four stages: self-indication,
      joint action, negotiation, and action. The meaning of hospital food and mealtimes
      differs from at-home food and mealtimes for the older adult, resulting in
      compromise. Intervention, which enhances the meaning of food and mealtimes for
      the older adult during hospitalization, may improve dietary intake and
      nutritional outcomes.

PMID- 24094449
TI  - Clinical and therapeutic implications of Sprouty2 feedback dysregulation in BRAF
      V600E-mutation-positive papillary thyroid cancer.
AB  - BACKGROUND: The BRAF V600E (BRAF+) mutation activates the mitogen-activated
      protein kinase (MAPK/ERK) pathway and may confer an aggressive phenotype in
      papillary thyroid cancer (PTC). Clinically, the behavior of BRAF+ PTC, however,
      varies from an indolent to an aggressive course. SPRY2 is a negative feedback
      regulator of the MAPK/ERK pathway. We hypothesize that the level of SPRY2
      expression contributes to MAPK/ERK pathway output and accounts for BRAF+ and
      clinical heterogeneity. METHODS: A tissue microarray with BRAF-positive PTCs
      (BRAF+ PTCs) was constructed and analyzed for SPRY2 expression and MAPK/ERK
      output. Data were studied in the context of clinicopathologic factors to develop
      a risk stratification system predictive of tumor biology. SPRY2 function was
      studied by silencing SPRY2 in BRAF+ PTC cells. These cells were treated with
      MAPK/ERK pathway inhibitors and assessed for growth effects. RESULTS: BRAF+ PTCs
      with an intact MAPK/ERK feedback pathway do not exhibit lymph node metastases.
      BRAF+ PTCs with dysregulated feedback pathways have nodal metastasis. When SPRY2
      is silenced, the BRAF+ PTC cells are significantly more sensitive to MAPK/ERK
      inhibition. CONCLUSION: PTC behavior likely is dependent on both the driver of
      the MAPK/ERK pathway and its regulatory feedback. When the feedback pathway is
      intact, the tumor phenotype seems to be less aggressive. This observation has
      direct and important clinical implications and may alter our treatment
      strategies.

PMID- 24094451
TI  - The value of thyroglobulin in washout of fine needle aspirate from 16 cervical
      lesions in patients with thyroid cancer.
AB  - BACKGROUND AND OBJECTIVE: Thyroglobulin in the needle washout (Tg-FNA) and
      cytology of fine needle aspiration (cyto-FNA) are recommended for diagnosis of
      metastatic lymphadenopathies and recurrence of differentiated thyroid cancer. The
      objective of this study was to assess the value of these procedures in 16
      cervical masses from patients with thyroid cancer of the follicular epithelium
      (TC). PATIENTS AND METHODS: The study included six patients with TC and cervical
      lymphadenopathies evaluated before initial thyroid surgery and 10 patients
      followed up after TC surgery with cervical lumps discovered. FNA was performed in
      all 16 masses. Results of cyto-FNA, Tg-FNA and of the combined tests were
      compared to the final diagnosis of each lesion. RESULTS: Among 10 lesions proven
      to be malignant at surgery, cyto-FNA, Tg-FNA and the combination of both allowed
      for adequate diagnosis in 7, 9, and 10 cases respectively. Among 6 lesions
      considered to be benign, cyto-FNA was able to confirm diagnosis in 4, was non
      diagnostic in one, and was falsely negative in the remaining case, while Tg-FNA
      was below the established cut-off value (to consider malignancy) in all cases.
      CONCLUSIONS: In patients with TC and suspect cervical masses, Tg-FNA improved the
      diagnostic yield of cyto-FNA alone, thus warranting its routine recommendation
      when FNA is performed. However, universal standardization of the technique and
      definition of valid cut-off thyroglobulin values (depending on the immunoassay
      used) above which the lesion should be considered to be malignant are still
      pending.

PMID- 24094452
TI  - Epidemiologic trends in pediatric tinea capitis: a population-based study from
      Kaiser Permanente Northern California.
AB  - BACKGROUND: Epidemic levels of tinea capitis (TC) have previously been reported
      in children. OBJECTIVE: We sought to determine new epidemiologic trends for TC
      among northern California children from 1998 through 2007. METHODS: Annual
      incidence of TC was based on diagnosis code or first-time antifungal
      prescriptions in all children up to age 15 years at Kaiser Permanente Northern
      California. RESULTS: An average of 672,373 children/y met the inclusion criteria.
      Trend analyses showed decreases in TC by diagnosis code and by prescriptions
      (73.7% and 23.7%, respectively). Girls had lower incidence rates than boys by
      diagnosis (111.9 vs 146.4, P < .001 for 1998, and 27.9 vs 39.9, P < .001 for
      2007). African Americans had the highest incidence rates by diagnosis (447.3 in
      1998 and 184.1 in 2007) compared with other ethnic groups. Trichophyton tonsurans
      was the predominant organism (89.4% of all positive fungal cultures in 1998 and
      91.8% in 2007). Prescriptions for griseofulvin declined, whereas the
      prescriptions for other antifungals increased. LIMITATIONS: This was a
      retrospective study. CONCLUSIONS: In this cohort, there was a significant
      decrease in incidence of TC over the study period. Trichophyton tonsurans
      continued to be the predominant organism. These trends may be a result of
      improved education, recognition, diagnosis, and treatment of TC and increased use
      of new oral antifungals.

PMID- 24094453
TI  - Association of 25-hydroxyvitamin D serum levels and metabolic parameters in
      psoriatic patients with and without arthritis.
AB  - BACKGROUND: Psoriasis has been related to a higher prevalence of cardiovascular
      risk factors. Vitamin-D deficiency has been associated with metabolic syndrome,
      cardiovascular disease, and psoriasis. However, there has been no comparative
      study on the effects of vitamin-D status between patients with and without
      psoriatic arthritis. OBJECTIVE: The objective was to assess the relationship of
      25-hydroxyvitamin D [25-(OH)D] levels with lipid and glucose metabolism
      parameters in psoriatic patients with and without arthritis. METHODS: We studied
      122 patients with psoriasis (61 without arthritis and 61 with arthritis) from the
      psoriasis unit (dermatology department) and rheumatology department of our
      hospital, analyzing lipid and glucose metabolism variables and serum 25-(OH)D
      concentrations. Measurements were conducted within a 2-month period to minimize
      seasonal bias in 25-(OH)D levels. RESULTS: In the psoriatic patients without
      arthritis, serum 25-(OH)D levels were inversely correlated with fasting glucose
      (r = -0.285; P = .026), total cholesterol (r = -0.440; P = .000), low-density
      lipoprotein (r = -0.415; P = .001), total cholesterol/high-density lipoprotein (r
      = -0.303; P = .01), and triglyceride (r = -0.280; P = .029) values. This
      association remained statistically significant for glucose, total cholesterol,
      and low-density lipoprotein after controlling for confounding factors in
      multivariate analysis. No association was found between serum 25-(OH)D levels and
      any metabolic parameter in the patients with psoriatic arthritis. LIMITATIONS:
      This is a cross-sectional study that supports the hypothesis of an association
      between vitamin D and metabolic parameters but does not establish a causal
      relationship. CONCLUSIONS: Serum 25-(OH)D was inversely related to lipid and
      glucose metabolism parameters in psoriatic patients without arthritis, whereas no
      such association was observed in psoriatic patients with arthritis.
      Interventional studies are warranted to assess the effects of vitamin-D
      supplements on the metabolic profile of psoriatic patients without arthritis.

PMID- 24094454
TI  - Finite element modeling of impulsive excitation and shear wave propagation in an
      incompressible, transversely isotropic medium.
AB  - Elastic properties of materials can be measured by observing shear wave
      propagation following localized, impulsive excitations and relating the
      propagation velocity to a model of the material. However, characterization of
      anisotropic materials is difficult because of the number of elasticity constants
      in the material model and the complex dependence of propagation velocity relative
      to the excitation axis, material symmetries, and propagation directions. In this
      study, we develop a model of wave propagation following impulsive excitation in
      an incompressible, transversely isotropic (TI) material such as muscle. Wave
      motion is described in terms of three propagation modes identified by their
      polarization relative to the material symmetry axis and propagation direction.
      Phase velocities for these propagation modes are expressed in terms of five
      elasticity constants needed to describe a general TI material, and also in terms
      of three constants after the application of two constraints that hold in the
      limit of an incompressible material. Group propagation velocities are derived
      from the phase velocities to describe the propagation of wave packets away from
      the excitation region following localized excitation. The theoretical model is
      compared to the results of finite element (FE) simulations performed using a
      nearly incompressible material model with the five elasticity constants chosen to
      preserve the essential properties of the material in the incompressible limit.
      Propagation velocities calculated from the FE displacement data show complex
      structure that agrees quantitatively with the theoretical model and demonstrates
      the possibility of measuring all three elasticity constants needed to
      characterize an incompressible, TI material. 

PMID- 24094456
TI  - Prospects for fetal surgery.
AB  - Until about forty years ago, the womb shielded the fetus from observation and
      therapy. The rapid changes in the diagnosis and treatment of human fetal
      anatomical abnormalities are due to improved fetal imaging studies as well as
      fetal sampling techniques (e.g. amniocentesis, chorionic villus sampling), and a
      better understanding of fetal pathophysiology derived from laboratory animals.
      Fetal therapy is the logical culmination of progress in fetal diagnosis. In other
      words, the fetus is now a patient. The fetal surgical treatment of the most
      severe form of spina bifida - myelomeningocele (MMC) - will be used as a paradigm
      to illustrate progress in and future prospects for fetal surgery. This review
      will focus on the rationale for in utero repair in the context of pathologic
      observations and animal models of MMC, outcomes from human fetal MMC repair
      including the recently completed Management of Myelomeningocele Study (MOMS
      trial), and future research directions. 

PMID- 24094457
TI  - Management of congenital femoral deficiency.
AB  - Abnormalities that affect the developing human limb range from subtle differences
      that are of no functional or cosmetic consequence, to complete absence of all
      limbs. Advances in non-invasive imaging have improved antenatal detection of
      these conditions and has broadened the options available to prospective parents.
      This paper considers congenital femoral deficiency and includes an overview of
      limb bud development and the mechanisms involved in normal growth. The use of
      ultrasound in antenatal screening and the clinical and radiological features in
      childhood will be discussed in addition to management including surgical
      reconstruction and prosthetic use. This should be one component of a
      multidisciplinary approach to provide the parents of an affected child with
      balanced information on functional prognosis, management choices and implications
      for future pregnancies. 

PMID- 24094458
TI  - Non-invasive prenatal testing for fetal sex determination: is ultrasound still
      relevant?
AB  - Early prenatal diagnosis of fetal sex is necessary to optimize pregnancy
      management in families known to be at risk of some heritable disorders. The
      demonstration of cell-free fetal DNA (cffDNA) in the mother's blood has made it
      possible to identify Y chromosome sequences in maternal blood and to determine
      fetal sex noninvasively, during the first trimester. This procedure can
      significantly reduce the number of invasive procedures for women with fetuses at
      risk of sex-linked diseases and optimize the management of these pregnancies.
      Fetal sex can be diagnosed by ultrasound with the same sensitivity and
      specificity, but later in pregnancy. We performed a review of the published
      literature evaluating the use of cffDNA and ultrasound for prenatal determination
      of fetal sex during the first trimester of pregnancy. We present the feasibility
      of the two methods and their impact on clinical practice. We applied a sensitive
      search of multiple bibliographic databases including Pubmed (MEDLINE), EMBASE,
      the Cochrane Library and Web of science between 1998 and 2013. Sixteen reports of
      the determination of fetal sex in maternal blood and 13 reports of the
      determination by ultrasound met our inclusion criteria. We found a sensitivity
      and specificity of nearly 100% from 8 weeks of gestation for cffDNA and from 13
      weeks of gestation for ultrasound respectively. Based on this review, we conclude
      that fetal sex can be determined with a high level of accuracy by analyzing
      cffDNA and at an earlier gestation than ultrasound. Ten years after the first
      feasibility study, the French National Authority for Health (HAS) released a
      technological assessment report on the determination of fetal sex in maternal
      blood, which has resulted in validating this test for reimbursement by the
      national health insurance fund for the following indications: X-linked recessive
      disease and congenital adrenal hyperplasia. 

PMID- 24094459
TI  - Characteristics, prevalence, risk factors, and underlying mechanism of
      hyponatremia in elderly patients treated with antidepressants: a cross-sectional
      study.
AB  - OBJECTIVES: The aims of this study were to describe the characteristics of
      hyponatremia in elderly users of antidepressants, to determine the prevalence and
      risk factors for hyponatremia, and to identify the underlying mechanisms. STUDY
      DESIGN: Cross-sectional study (March 2007-April 2009) with prospectively
      collected data. Patients were older than 60 years, used antidepressants, and had
      a complete geriatric assessment. MAIN OUTCOME MEASURES: Serum sodium and
      antidiuretic hormone levels, serum osmolality, urine sodium level, and urine
      osmolality were measured. The prevalence of hyponatremia (serum sodium <135 mM)
      as an adverse reaction to an antidepressant (AR-AD), defined with Naranjo's
      algorithm, was calculated. Hyponatremic patients were compared to normonatremic
      patients with regard to gender, age, weight, history of hyponatremia,
      hyponatremia-associated medications and disorders, and type and duration of
      antidepressant use. RESULTS: Of 358 eligible patients, 345 were included. The
      prevalence of hyponatremia as an AR-AD was 9.3%. Risk factors were a history of
      hyponatremia (adjusted OR 11.17, 95%CI 2.56-40.41), weight<60 kg (adjusted OR
      3.47, 95%CI 1.19-10.13), and psychosis (adjusted OR 3.62, 95%CI 1.12-11.73). Non
      suppressed ADH was found in a minority of hyponatremic patients. CONCLUSIONS: In
      elderly patients, the prevalence of hyponatremia as adverse reaction to all types
      of antidepressants was 9%. Patients with previous hyponatremia, weight <60 kg,
      and psychosis were at risk. Beside SIADH, the nephrogenic syndrome of
      inappropriate antidiuresis, in which ADH secretion was normal, is postulated as
      an underlying mechanism. This has consequences for treatment of antidepressant
      induced hyponatremia with vasopressin receptor antagonists.

PMID- 24094460
TI  - Visualization of inflammation and demyelination in 2D2 transgenic mice with
      rodent MRI.
AB  - Research tools are urgently needed to elucidate the specificities of NMO and MS
      due to their clinical similarity at the early stage of the diseases. Herein,
      using high-field-strength MRI we characterized the optic nerve and spinal cord
      lesions in 2D2(tg) mice (MOG 35-55 specific TCR). Specifically, early Blood-brain
      Barrier breakdown was observed in 86% of the 2D2(tg) mice, while the majority of
      mice showed little to no brain lesions. Further, immunohistology showed
      inflammatory infiltrates and demyelination in the brain and spinal cord that
      mirrored sites of MRI lesions, along with a decrease in AQP4 protein at lesion
      sites. Collectively, 2D2(tg) mice develop optic and spinal cord lesions that can
      be visualized by high-field rodent MRI and verified by pathological assessment.
      The similarity of these lesions with those seen in NMO patients suggests that the
      2D2(tg) mouse might serve as a model for NMO research. 

PMID- 24094462
TI  - The involvement of InMIR167 in the regulation of expression of its target gene
      InARF8, and their participation in the vegetative and generative development of
      Ipomoea nil plants.
AB  - The plant hormone auxin plays a critical role in regulating plant growth and
      development. Recent advances have been made that having improved our
      understanding of auxin response pathways, primarily by characterizing the genes
      encoding auxin response factors (ARFs) in Arabidopsis. In addition, the
      expression of some ARFs is regulated by microRNAs (miRNAs). In Arabidopsis
      thaliana, ARF6 and ARF8 are targeted by miR167, whereas ARF10, ARF16 and ARF17
      are targeted by miR160. Nevertheless, little is known about any possible
      interactions between miRNAs and the auxin signaling pathway during plant
      development. In this study, we isolated the miR167 target gene InARF8 cDNA from
      the cotyledons of the short day plant (SDP) Ipomoea nil (named also Pharbitis
      nil). Additionally, the In-miR167 precursor was identified from the I. nil EST
      database and analyses of InARF8 mRNA, In-pre-miR167 and mature miR167
      accumulation in the plant's vegetative and generative organs were performed. The
      identified cDNA of InARF8 contains a miR167 complementary sequence and shows
      significant similarity to ARF8 cDNAs of other plant species. The predicted amino
      acid sequence of InARF8 includes all of the characteristic domains for ARF family
      transcription factors (B3 DNA-binding domain, AUX/IAA-CTD and a glutamine-rich
      region). Quantitative RT-PCR reactions and in situ hybridization indicated that
      InARF8 was expressed primarily in the shoot apices, leaf primordia and hypocotyls
      of I. nil seedlings, as well as in flower pistils and petals. The InARF8
      transcript level increased consistently during the entire period of pistil
      development, whereas in the stamens, the greatest transcriptional activity
      occurred only during the intensive elongation phase. Additionally, an expression
      analysis of both the precursor In-pre-miR167 molecules identified and mature
      miRNA was performed. We observed that, in most of the organs examined, the InARF8
      expression pattern was opposite to that of MIR167, indicating that the gene's
      activity was regulated by mRNA cleavage. Our findings suggested that InARF8 and
      InMIR167 participated in the development of young tissues, especially the shoot
      apices and flower elements. The main function of MIR167 appears to be to regulate
      InARF8 organ localization.

PMID- 24094461
TI  - Transcriptome analysis of HIV-infected peripheral blood monocytes: gene
      transcripts and networks associated with neurocognitive functioning.
AB  - Immunologic dysfunction, mediated via monocyte activity, has been implicated in
      the development of HIV-associated neurocognitive disorder (HAND). We hypothesized
      that transcriptome changes in peripheral blood monocytes relate to neurocognitive
      functioning in HIV+ individuals, and that such alterations could be useful as
      biomarkers of worsening HAND. METHODS: mRNA was isolated from the monocytes of 86
      HIV+ adults and analyzed with the Illumina HT-12 v4 Expression BeadChip.
      Neurocognitive functioning, HAND diagnosis, and other clinical and virologic
      variables were determined. Data were analyzed using standard expression analysis
      and weighted gene co-expression network analysis (WGCNA). RESULTS: Neurocognitive
      functioning was correlated with multiple gene transcripts in the standard
      expression analysis. WGCNA identified two nominally significant co-expression
      modules associated with neurocognitive functioning, which were enriched with
      genes involved in mitotic processes and translational elongation. CONCLUSIONS:
      Multiple modified gene transcripts involved in inflammation, cytoprotection, and
      neurodegeneration were correlated with neurocognitive functioning. The
      associations were not strong enough to justify their use as biomarkers of HAND;
      however, the associations of two co-expression modules with neurocognitive
      functioning warrant further exploration.

PMID- 24094463
TI  - Bioequivalence of two intravenous formulations of antithrombin III: a two-way
      crossover study in healthy Korean subjects.
AB  - BACKGROUND: Treatment with antithrombin (AT)-III is indicated for patients with
      sepsis or hereditary AT deficiency. OBJECTIVE: The purpose of this study was to
      compare the pharmacokinetic and pharmacodynamic characteristics of 2 AT-III
      formulations in healthy Korean volunteers to satisfy the regulatory requirements
      for bioequivalence for marketing purposes. METHODS: A single-center, single-dose,
      open-label, randomized, 2-period, 2-sequence crossover study was conducted in
      healthy Korean volunteers. Blood samples for the drug analysis were collected for
      up to 216 hours after drug administration. Participants received either the test
      or reference formulation of AT-III 100 U/kg IV for 20 minutes in the first period
      and the alternative formulation in the second period. Both the AT-III activity
      and antigen (Ag) were measured for the analysis of pharmacokinetic properties,
      and the prothrombin time and the activated partial thromboplastin time were
      assessed for the analysis of pharmacodynamic properties. Because AT-III is an
      endogenous compound, the analysis used data corrected from baseline values. The
      tolerability of the 2 formulations was also assessed based on physical
      examinations including vital sign measurements, laboratory tests, and 12-lead
      ECG. RESULTS: Of the 20 subjects enrolled (mean [SD] age, height, and weight,
      25.3 [2.3] years, 175.3 [4.5] cm, and 67.4 [6.3] kg, respectively), 19 completed
      both treatment periods; 1 subject withdrew consent for personal reasons. The
      observed mean (SD) Cmax, AUClast, and AUC0-infinity of AT-III activity were,
      respectively, 279.24% (35.92), 14,364.10 (2325.25) %.h, and 17,526.38 (3150.81)
      %.h with the test formulation and 249.75% (31.96), 12,962.95 (1897.52) %.h, and
      15,957.67 (3189.21) %.h with the reference formulation. The observed mean (SD)
      Cmax, AUClast, and AUC0-infinity of AT-III Ag were 62.58 (5.66) mg/dL, 3051.94
      (401.87) mg/dL.h, and 3639.80 (726.01) mg/dL.h, respectively, with the test
      formulation and 58.63 (5.27) mg/dL, 2805.08 (272.38) mg/dL.h, and 3340.00
      (428.46) mg/dL.h with the reference formulation. The geometric mean ratios (90%
      CI) of the log-transformed data for AT-III activity between the 2 formulations
      were 1.11494 (1.08994-1.14053) for Cmax, 1.11305 (1.05435-1.17503) for AUClast,
      and 1.11527 (1.03754-1.19889) for AUC0-infinity; corresponding values for AT-III
      Ag were 1.08802 (1.06258-1.11405), 1.10905 (1.05804-1.16242), and 1.11460
      (1.02058-1.21726). During the study period, 8 adverse events were reported, and
      all were transient, mild, and resolved completely during the treatment period.
      CONCLUSION: The results of the present study showed that these 2 AT-III
      formulations met the regulatory criteria for pharmacokinetic bioequivalence with
      respect to AT-III activity and Ag in these healthy Korean subjects.
      ClinicalTrials.gov identifier: NCT00846274.

PMID- 24094464
TI  - Exposure-response (safety) analysis to identify linifanib dose for a Phase III
      study in patients with hepatocellular carcinoma.
AB  - BACKGROUND: Hepatocellular carcinoma (HCC) is the third most common cause of
      cancer-related deaths and the fifth most common cancer globally. Hepatocellular
      carcinoma produces highly vascular tumors that overexpress vascular endothelial
      growth factor (VEGF), thus making VEGF a promising therapeutic target. The
      competitive inhibitor linifanib (ABT-869) has selectivity for VEGF and platelet
      derived growth factor (PDGF) receptors and minimal activity against unrelated
      tyrosine and serine and threonine kinases. However, the optimal dosing regimen
      for linifanib in HCC patients is not yet known. OBJECTIVE: This study attempts to
      identify a linifanib dose or dosing regimen with an acceptable safety profile for
      a Phase III study in HCC patients. METHODS: The pharmacokinetic (PK) properties
      of linifanib were characterized from 2 Phase I and 3 Phase II clinical trials. Of
      the 266 patients evaluated, the median weight was 68 kg (range, 35-177 kg), 64%
      were male, and 87.6% of patients received an oral solution of linifanib, whereas
      12.4% received a tablet formulation. Approximately 95% of patients received drug
      based on weight, with the remaining on a fixed-dosing regimen. A population PK
      analysis was conducted to characterize the linifanib exposure for each patient.
      Linifanib Cmax and AUC derived from the population PK properties were correlated
      with the rates of adverse events (AEs). RESULTS: Linifanib PK properties are dose
      proportional for the 0.10-mg/kg to 0.25-mg/kg once daily dose range and are time
      independent after repeated oral dosing. The Tmax of linifanib is approximately 3
      hours, and the t1/2 is approximately 1 day. The most common AEs related to
      linifanib PK were hypertension (P = 0.02 for Cmax and P = 0.01 for AUC), diarrhea
      (P = 0.001 for Cmax and P = 0.0012 for AUC), proteinuria (P = 0.001 for Cmax and
      P = 0.002 for AUC), and asthenia (P = 0.03 for AUC). Weight and sex were
      identified as covariates for Cmax, and sex was identified as a covariate for AUC.
      The predicted AE range for females was slightly higher compared with males;
      however, the AE range is tighter for the weight range for fixed dosing compared
      with weight-based dosing, regardless of sex. CONCLUSIONS: The PK properties of
      linifanib support a one-compartment model with first-order absorption and
      elimination. Comparison of weight-based and fixed dosing revealed predicted AE
      rates to be similar, with a tighter AE range for fixed dosing. The safety profile
      of linifanib, therefore, supports a 17.5 mg fixed starting dose for Phase III
      clinical studies.

PMID- 24094465
TI  - Ceftazidime dosage recommendations in burn patients: from a population
      pharmacokinetic approach to clinical practice via Monte Carlo simulations.
AB  - BACKGROUND: Ceftazidime dosage regimen recommendations based on
      pharmacokinetic/pharmacodynamic approaches are not available for burn patients.
      OBJECTIVE: The goal of this study was to propose a continuous dosage regimen of
      ceftazidime in burn patients, taking into account different MICs and
      pharmacokinetic covariates. METHODS: The population pharmacokinetic analysis was
      conducted by using software dedicated to the analysis of nonlinear mixed effects
      models. The population pharmacokinetic model was first developed and validated in
      70 adult burn patients. Taking into account various MICs of pathogens, 3 Monte
      Carlo simulation trials were conducted by using target concentration intervals
      (10-100, 20-100, and 40-100 mg/L). The recommended dosages were defined as the
      minimum dose leading to the highest percentage of patients whose ceftazidime
      concentrations were included in the target interval. RESULTS: Serum creatinine
      and age were identified as covariates of ceftazidime clearance. Age was also
      involved in volume of distribution. The simulations showed that a dose of 6 g/d
      did not allow achievement of the target interval in most patients. Regardless of
      dosage regimen, age, and serum creatinine, the mean percentage of patients
      reaching the 10- to 100-mg/L and the 20- to 100-mg/L target intervals were 99.4%
      (0.3%) and 96.1% (0.8%), respectively. For the 40- to 100-mg/L target interval,
      this percentage was only 76.4% (2.1%) (range, 65%-80%). CONCLUSIONS: Age and
      serum creatinine level can be used at the bedside to determine the initial doses
      of ceftazidime. These Monte Carlo simulations highlight the need of a reappraisal
      of ceftazidime's use in burn patients. Doses between 3 and 16 g/d are proposed,
      taking into account the pathogens' MICs. However, for sepsis caused by a pathogen
      with an MIC >= 8 mg/L, an insufficient percentage of burn patients will reach the
      therapeutic target with the recommended dosages.

PMID- 24094466
TI  - Endoscopic papillectomy: risk factors for incomplete resection and recurrence
      during long-term follow-up.
AB  - BACKGROUND: Endoscopic papillectomy is increasingly used as an alternative to
      surgery for ampullary adenomas and other noninvasive ampullary lesions.
      OBJECTIVE: To measure short-term safety and efficacy of endoscopic papillectomy,
      define patient and lesion characteristics associated with incomplete endoscopic
      resection, and measure adenoma recurrence rates during long-term follow-up.
      DESIGN: Retrospective cohort study. SETTING: Tertiary-care academic medical
      center. PATIENTS: All patients who underwent endoscopic papillectomy for
      ampullary lesions between July 1995 and June 2012. INTERVENTION: Endoscopic
      papillectomy. MAIN OUTCOME MEASUREMENTS: Patient and lesion characteristics
      associated with incomplete endoscopic resection and ampullary adenoma-free
      survival analysis. RESULTS: We identified 182 patients who underwent endoscopic
      papillectomy, 134 (73.6%) having complete resection. Short-term adverse events
      occurred in 34 (18.7%). Risk factors for incomplete resection were jaundice at
      presentation (odds ratio [OR] 0.21; 95% confidence interval [CI] 0.07-0.69; P =
      .009), occult adenocarcinoma (OR 0.06; 95% CI, 0.01-0.36; P = .002), and
      intraductal involvement (OR 0.29; 95% CI, 0.11-0.75; P = .011). The en bloc
      resection technique was strongly associated with a higher rate of complete
      resection (OR 4.05; 95% CI, 1.71-9.59; P = .001). Among patients with ampullary
      adenoma who had complete resection (n = 107), 16 patients (15%) developed
      recurrence up to 65 months after resection. LIMITATIONS: Retrospective analysis.
      CONCLUSION: Jaundice at presentation, occult adenocarcinoma in the resected
      specimen, and intraductal involvement are associated with a lower rate of
      complete resection, whereas en bloc papillectomy increases the odds of complete
      endoscopic resection. Despite complete resection, recurrence was observed up to 5
      years after papillectomy, confirming the need for long-term surveillance.

PMID- 24094467
TI  - Video demonstration of the introducer-type percutaneous gastrostomy system.

PMID- 24094468
TI  - Colonoscopy quality improvement: practice to public health.

PMID- 24094469
TI  - Effect of dietary supplementation on the antimicrobial activity of blood
      leukocytes isolated from Holstein heifers.
AB  - The purpose of this investigation was to evaluate the effect of an
      immunostimulating feed supplement (OmniGen-AF(r)) on the antimicrobial properties
      of blood leukocytes in dairy heifers in an attempt to prevent mastitis. Blood
      leukocytes from supplemented and unsupplemented controls were used. Phagocytic
      activity and reactive oxygen species (ROS) production were studied on d 0 (prior
      to feed supplementation) and on days 30 and 60 after supplementation. L-selectin
      and IL-8R mRNA expressions on blood leukocytes were evaluated on d 0 (prior to
      feed supplementation) and monthly thereafter for 15 mo. On d 30 after
      supplementation, neutrophils from treated heifers exhibited greater binding and
      internalization of Escherichia coli and greater ROS production compared with
      unsupplemented controls. L-selectin mRNA expression was increased in supplemented
      heifers vs. controls; however, IL-8R mRNA expression was not different. Results
      support the continued study of dietary supplementation as an additional
      management tool to enhance udder health in dairy heifers.

PMID- 24094470
TI  - Comparative study of valved and nonvalved fully implantable catheters inserted
      via ultrasound-guided puncture for chemotherapy.
AB  - BACKGROUND: Fully implantable catheters are important for oncology treatments.
      They can be functionally categorized as valved or nonvalved. Theoretically, a
      valve prevents spontaneous blood reflux into the catheter, reducing the incidence
      of complications. We sought to compare the results from the implantation of
      valved and nonvalved fully implantable 8-French catheters inserted via ultrasound
      guided puncture in cancer patients undergoing chemotherapy treatment. METHODS: A
      retrospective analysis of 100 patients who underwent long-term catheter
      implantation guided by ultrasound was performed looking for early (<=30 days) or
      late (>=90 days) complications. They were evaluated regarding the use of valved
      or nonvalved catheter and assessed on univariate model. RESULTS: The only early
      complication (hematoma) was identified in the valved group. Twenty-two late
      complications were identified (72.72% in the valved group and 27.27% in the
      nonvalved group; P = 0.009). Blood reflux dysfunction, which occurred in 12
      patients in the valved and none in the nonvalved devices group, was the only
      complication with an incidence that was significantly different between the
      groups. CONCLUSION: Fully implantable valved catheters with Groshong (Bard
      Medical Division, Covington, GA) valves have a higher rate of blood reflux
      dysfunction compared with nonvalved catheters, but this did not interfere with
      the efficacy of the treatment.

PMID- 24094471
TI  - Eating disorders and bone.
AB  - Low bone mineral density (BMD) is a frequent and often-overlooked consequence of
      eating disorders, in particular anorexia nervosa and eating disorders associated
      with the female athlete triad. The causes of low BMD are multifactorial and
      include low peak bone mass accrual, accelerated bone resorption, and changes in
      bone microarchitecture. Early diagnosis and interventions focused on nutritional
      rehabilitation and weight gain reduce the risk of further BMD deficits and
      fractures. 

PMID- 24094472
TI  - Does a high dietary acid content cause bone loss, and can bone loss be prevented
      with an alkaline diet?
AB  - A popular concept in nutrition and lay literature is that of the role of a diet
      high in acid or protein in the pathogenesis of osteoporosis. A diet rich in fruit
      and vegetable intake is thought to enhance bone health as the result of its
      greater potassium and lower "acidic" content than a diet rich in animal protein
      and sodium. Consequently, there have been a number of studies of diet
      manipulation to enhance potassium and "alkaline" content of the diet to improve
      bone density or other parameters of bone health. Although acid loading or an
      acidic diet featuring a high protein intake may be associated with an increase in
      calciuria, the evidence supporting a role of these variables in the development
      of osteoporosis is not consistent. Similarly, intervention studies with a more
      alkaline diet or use of supplements of potassium citrate or bicarbonate have not
      consistently shown a bone health benefit. In the elderly, inadequate protein
      intake is a greater problem for bone health than protein excess. 

PMID- 24094473
TI  - Magnitude of forward trunk flexion influences upper limb muscular efforts and
      dynamic postural stability requirements during sitting pivot transfers in
      individuals with spinal cord injury.
AB  - The purpose of this study was to investigate the effects of imposing different
      degrees of forward trunk flexion during sitting pivot transfers on
      electromyographic activity at the leading and trailing upper limb muscles and on
      dynamic stability requirements. Thirty-two individuals with a spinal cord injury
      performed three types of sitting pivot transfers: natural technique, exaggerated
      forward trunk flexion and upright trunk position. Ground reaction forces, trunk
      kinematics, and bilateral electromyographic activity of eight upper limb muscles
      were recorded. Electromyographic data were analyzed using the area under the
      curve of the muscular utilization ratio. Dynamic stability requirements of
      sitting pivot transfers were assess using a dynamic equilibrium model. Compared
      to the natural strategy, significantly greater muscle activities were found for
      the forward trunk flexion condition at the anterior deltoid and both heads of the
      pectorialis major, whereas the upright trunk strategy yielded greater muscle
      activity at the latissimus dorsii and the triceps. The forward flexed condition
      was found to be more dynamically stable, with a lower stabilizing force,
      increased area of base of support and greater distance traveled. Thus,
      transferring with a more forward trunk inclination, even though it increases work
      of few muscles, may be a beneficial trade-off because increased dynamic stability
      of this technique and versatility in terms of potential distance of the transfer.

PMID- 24094476
TI  - A comparison of two open surgical cricothyroidotomy techniques by military medics
      using a cadaver model.
AB  - STUDY OBJECTIVE: The CricKey is a novel surgical cricothyroidotomy device
      combining the functions of a tracheal hook, stylet, dilator, and bougie
      incorporated with a Melker airway cannula. This study compares surgical
      cricothyroidotomy with standard open surgical versus CricKey technique. METHODS:
      This was a prospective crossover study using human cadaveric models. Participants
      included US Army combat medics credentialed at the emergency medical technician
      basic level. After a brief anatomy review and demonstration, participants
      performed in random order standard open surgical cricothyroidotomy and CricKey
      surgical cricothyroidotomy. The primary outcome was first-pass success, and the
      secondary outcome measure was procedural time. RESULTS: First-attempt success was
      100% (15/15) for CricKey surgical cricothyroidotomy and 66% (10/15) for open
      surgical cricothyroidotomy (odds ratio 16.0; 95% confidence interval 0.8 to 326).
      Surgical cricothyroidotomy insertion was faster for CricKey than open technique
      (34 versus 65 seconds; median time difference 28 seconds; 95% confidence interval
      16 to 48 seconds). CONCLUSION: Compared with the standard open surgical
      cricothyroidotomy technique, military medics demonstrated faster insertion with
      the CricKey. First-pass success was not significantly different between the
      techniques.

PMID- 24094477
TI  - 'Retouch free': The effect of labelling media images as not digitally altered on
      women's body dissatisfaction.
AB  - This study aimed to investigate the effect of 'retouch free' labels on thin ideal
      fashion images on women's body dissatisfaction. This represents an experimental
      analogue to current practice by some fashion magazines. Participants were 224
      female undergraduates who viewed a set of fashion shoots with either no label, or
      a label indicating that the image had not been digitally altered. Results
      indicated that, although body dissatisfaction increased after exposure to the
      thin ideal images, there was no significant effect of label type on mood or body
      dissatisfaction. It was concluded that labelling images as digitally unaltered
      appears neither helpful nor harmful in terms of body dissatisfaction.
      Nevertheless, more extensive research is required to guide the most effective use
      of labels. 

PMID- 24094478
TI  - Re-evaluating our perspective on retinal artery occlusion from carotid
      dissection: a report of three cases and review of the literature.
AB  - BACKGROUND AND OBJECTIVE: Retinal artery occlusion from carotid dissection is
      rare and classically considered a post-traumatic phenomenon occurring in young
      patients and associated with additional symptoms of dissection such as neck pain,
      headache, or focal neurological deficits. PATIENTS AND METHODS: The authors
      report three cases of retinal artery occlusion due to carotid artery dissection
      and briefly review the literature. RESULTS: Antecedent trauma or neck injury was
      reported in only 42% (five of 12) of previously reported cases and in none of the
      three cases presented here. All three patients in this series initially denied
      symptoms such as headache or neck pain; however, one patient's wife later
      recalled her husband experiencing minor neck soreness several days prior to
      visual loss. In 17% (two of 12) of previously reported cases, no additional
      symptoms of carotid dissection were reported. CONCLUSION: These cases highlight
      the importance of considering carotid dissection in young patients with retinal
      artery occlusion, even in the absence of a report of recent trauma or associated
      symptoms such as pain.

PMID- 24094480
TI  - Maternal fat intake during pregnancy and wheeze and eczema in Japanese infants:
      the Kyushu Okinawa Maternal and Child Health Study.
AB  - PURPOSE: This cohort study examined the relationship between maternal intake of
      individual fatty acids, meat, and fish during pregnancy and the risk of wheeze
      and eczema in children aged 23-29 months because epidemiologic evidence on this
      topic is inconclusive. METHODS: Subjects were 1354 Japanese mother-child pairs.
      Data on maternal intake during pregnancy were assessed with a validated diet
      history questionnaire. Data on symptoms of wheeze and eczema were based on
      criteria of the International Study of Asthma and Allergies in Childhood.
      RESULTS: Significant inverse exposure-response relationships were observed
      between maternal intake of eicosapentaenoic acid (EPA) and EPA plus
      docosahexaenoic acid (DHA) during pregnancy and infantile wheeze although the
      adjusted odds ratios between extreme quartiles fell just short of the
      significance level. No such inverse relationships were detected for infantile
      eczema. Maternal intake of total fat, saturated fatty acids, monounsaturated
      fatty acids, total n-3 polyunsaturated fatty acids (PUFA), alpha-linolenic acid,
      DHA, total n-6 PUFA, linoleic acid, arachidonic acid, cholesterol, fish, and meat
      and the ratio of n-3 to n-6 PUFA consumption were not significantly related to
      infantile wheeze or eczema. CONCLUSIONS: Higher maternal intake of EPA and EPA
      plus DHA during pregnancy may reduce the risk of infantile wheeze.

PMID- 24094479
TI  - [Malian first observation of disseminated African histoplasmosis with predominant
      bone localizations in an HIV-negative child in Bamako (Mali). Review of the
      literature].
AB  - Endemic deep fungal infections are still under recognised diseases in daily
      medical practice because of their rarity in sub-Saharan area. The African
      histoplasmosis Histoplasma capsulatum var. duboisii (H. capsulatum duboisii) is
      the most frequent variety described in Mali through limited studies in adult
      patients, since the first case described by Catanei and Kervran (1945). Our case
      report is a disseminated histoplasmosis in a young 6-year-old african child. He
      was male and rural. The infectious localisations were mucosae, skin, lymphnodes,
      urinary tract and bones. Evolution has been marred by an episode of worsening of
      symptoms despite initial clinical improvement with ketoconazole. After healing of
      mucocutaneous lesions, we noticed a limitation of ampliation of both wrists. The
      radiographic bone lesions were lysis of the right lower end of the right radius
      and cubitus and fragmentation of cubital epiphysis of the same arm. Lacunes were
      present on the fifth right finger in metatarsus and phalanx; lacune and blowing
      aspect of the second phalanx of the left third finger was noted. The disseminated
      form of African histoplasmosis may occur in HIV-negative subject. The prognosis
      depends on early diagnosis and administration of appropriate and well-conducted
      therapy. 

PMID- 24094482
TI  - Simultaneous detection of multiple microRNAs for expression profiles of microRNAs
      in lung cancer cell lines by capillary electrophoresis with dual laser-induced
      fluorescence.
AB  - MicroRNAs (miRNAs) are small, endogenous, single-stranded, noncoding RNAs.
      Circulating miRNAs are being considered as promising disease biomarkers. Indeed,
      single miRNAs have been associated with a wide variety of disease conditions and
      can target multiple mRNAs; therefore, several miRNAs may be simultaneously
      involved in disease progression and development. In this study, we developed a
      capillary electrophoresis with dual laser-induced fluorescence (CE with dual LIF)
      method using two color laser excitations for simultaneous determination of
      multiple miRNAs. Target miRNAs were hybridized with 6-FAM- or Cy5-labeled DNA
      probes for simultaneous determination of multiple miRNAs at excitation
      wavelengths of 488 and 635 nm. The hybridized miRNAs were separated using CE with
      dual LIF and detected within 13 min at excitation wavelengths of 488 and 635 nm
      without any interference or crosstalk. Additionally, the proposed approach was
      used successfully to detect and evaluate levels of several endogenous miRNAs from
      lung cancer cell lines. These results showed the potential of CE with dual LIF
      for fast, specific, simultaneous analysis of multiple miRNAs in cell extracts,
      biofluids, and tissues.

PMID- 24094483
TI  - Differential coulometric oxidation following post column-switching high pressure
      liquid chromatography for fluorescence measurement of unmetabolized folic acid in
      human plasma.
AB  - Although many countries have fortified their grain supplies with folic acid (FA)
      to decrease the incidence of neural tube defects, others have not due to concerns
      that this synthetic folate might have some adverse effects. Persistent
      unmetabolized FA has been found even in plasma from fasted subjects. To
      facilitate measurement of low levels of folic acid in human plasma, post-column
      coulometric oxidative cleavage was used to convert poorly fluorescent FA into a
      highly fluorescent compound determined to be 6-formyl-pterin. To minimize sample
      work-up and maximize recovery, column-switching HPLC transferred a window of
      eluate containing the FA from the first column (C8) onto a second column (phenyl
      hexyl). The pH of two mobile phases were adjusted to be above and then below a pK
      of the FA alpha-carboxyl group, thus promoting separation from compounds
      coeluting from the C8-column. This permitted sample preparation using only a
      simple high recovery protein precipitation. Definitive identification of FA in
      human plasma was accomplished by duplicate injections of sample with the
      electrochemical voltage set above and below its half-potential. The LOD (S/N=3)
      was 0.10 nM. The intra- and inter-assay CV's were 2.3% and 5%, respectively.
      Comparison of these results with those obtained by HPLC/MS/MS with stable isotope
      internal standard showed a slope of 1.00 +/- 0.019. This simple, sensitive, and
      repeatable assay facilitates a more thorough investigation of the response of
      various human populations to folic acid intake. Post-column differential
      coulometric electrochemistry can expand the variety of compounds amenable to
      fluorescence detection.

PMID- 24094484
TI  - Ultrasound-assisted surfactant-enhanced emulsification microextraction for the
      determination of carbamates in wines by ultra-high performance liquid
      chromatography-tandem mass spectrometry.
AB  - A new sensitive multiresidue method based on ultra-high performance liquid
      chromatography-tandem mass spectrometry (UHPLC-MS/MS) has been developed for the
      detection, confirmation and quantification of twenty five carbamates in wine
      samples. The separation was achieved in 5.5 min, using a Zorbax Eclipse plus RRHD
      C18 column (50 mm*2.1 mm, 1.8 MUm), with a mobile phase of water and methanol,
      both of them with 0.01% formic acid. The analytes were detected in positive mode
      with multiple reaction monitoring mode. Ultrasound-assisted surfactant-enhanced
      emulsification microextraction (UASEME), using a low-density extraction solvent
      has been optimized for the satisfactory extraction of carbamates and clean-up of
      extracts. The matrix effect was studied, showing that the proposed procedure
      provides very clean extracts. Under optimum conditions, recoveries for fortified
      wine samples ranged from 74 to 102%, with relative standard deviations lower than
      6%. Limits of quantification ranged from 0.15 to 0.92 MUgl(-1), showing the high
      sensitivity of this fast and simple method and its compliance with current
      requirements.

PMID- 24094485
TI  - Beyond genetic stability of mesenchymal stromal cells.

PMID- 24094486
TI  - Fetal mesenchymal stromal cells from cryopreserved human chorionic villi:
      cytogenetic and molecular analysis of genome stability in long-term cultures.
AB  - BACKGROUND AIMS: First-trimester chorionic villi (CV) are an attractive source of
      human mesenchymal stromal cells (hMSC) for possible applications in cellular
      therapy and regenerative medicine. Human MSC from CV were monitored for genetic
      stability in long-term cultures. METHODS: We set up a good manufacturing practice
      cryopreservation procedure for small amounts of native CV samples. After
      isolation, hMSC were in vitro cultured and analyzed for biological end points.
      Genome stability at different passages of expansion was explored by karyotype,
      genome-wide array-comparative genomic hybridization and microsatellite
      genotyping. RESULTS: Growth curve analysis revealed a high proliferative
      potential of CV-derived cells. Immunophenotyping showed expression of typical MSC
      markers and absence of hematopoietic markers. Analysis of multilineage potential
      demonstrated efficient differentiation into adipocytes, osteocytes, chondrocytes
      and induction of neuro-glial commitment. In angiogenic experiments,
      differentiation in endothelial cells was detected by in vitro Matrigel assay
      after vascular endothelial growth factor stimulation. Data obtained from
      karyotyping, array-comparative genomic hybridization and microsatellite
      genotyping comparing early with late DNA passages did not show any genomic
      variation at least up to passage 10. Aneuploid clones appeared in four of 14
      cases at latest passages, immediately before culture growth arrest. CONCLUSIONS:
      Our findings indicate that hCV-MSC are genetically stable in long-term cultures
      at least up to passage 10 and that it is possible to achieve clinically relevant
      amounts of hCV-MSC even after few stages of expansion. Genome abnormalities at
      higher passages can occasionally occur and are always associated with spontaneous
      growth arrest. Under these circumstances, hCV-MSC could be suitable for
      therapeutic purposes.

PMID- 24094487
TI  - Culture expansion induces non-tumorigenic aneuploidy in adipose tissue-derived
      mesenchymal stromal cells.
AB  - BACKGROUND AIMS: Adipose tissue-derived mesenchymal stromal cells (ASCs) are of
      interest as a cell therapeutic agent for immunologic and degenerative diseases.
      During in vitro expansion, ASCs may be at risk for genetic alterations, and
      genetic screening is a prerequisite. We examined the presence of aneuploidy in
      ASCs and its origin and development during culture and evaluated the implications
      of aneuploidy for therapeutic use of ASCs. METHODS: Adipose tissue of healthy
      individuals was used for isolation and expansion of ASCs. Chromosome copy numbers
      were studied using fluorescence in situ hybridization analysis. Aneuploidy was
      studied in freshly isolated ASCs, in ASCs cultured for 0-16 passages and in
      senescent cultures. To evaluate the plasticity of ploidy, ASCs were cloned, and
      the variation of ploidy in the clones was examined. Tumorigenicity was studied by
      subcutaneous injection of aneuploid ASCs in immunodeficient NOD/SCID mice.
      RESULTS: No aneuploidy was detected in freshly isolated ASCs. In low passages
      (passages 0-4), aneuploidy was detected in 3.4% of ASCs. Prolonged culture
      expansion of ASCs (passages 5-16) resulted in a significant increase of
      aneuploidy to 7.1%. With senescence, aneuploidy increased further to 19.8%.
      Aneuploidy was observed in clones of diploid ASCs, demonstrating the de novo
      development of aneuploidy. No transformation of ASCs was observed, and in
      contrast to cancer cell lines, aneuploid ASCs were incapable of tumor formation
      in immunodeficient mice. CONCLUSIONS: ASC cultures contain a stable percentage of
      aneuploid cells. Aneuploidy was not a predecessor of transformation or tumor
      formation. This finding indicates that aneuploidy is culture-induced but unlikely
      to compromise clinical application of ASCs.

PMID- 24094488
TI  - Genomic alterations in human umbilical cord-derived mesenchymal stromal cells
      call for stringent quality control before any possible therapeutic approach.
AB  - BACKGROUND AIMS: The umbilical cord (UC) is a promising source of mesenchymal
      stromal cells (MSCs). UC-MSCs display very similar in vitro characteristics to
      bone marrow-MSCs and could represent a valuable alternative for cell-based
      therapies. However, it is still unclear whether UC-MSCs are prone or not to the
      acquisition of genomic imbalances during in vitro expansion. METHODS: With the
      use of array-comparative genomic hybridization, we compared copy number
      variations of early (P2-P3) and late (>P5) passages of in vitro-expanded UC-MSCs.
      RESULTS: In two of 11 long-term UC-MSCs cultures, we observed the appearance of
      clones carrying genomic imbalances, which generated genetic mosaicism at
      intermediate passages. Although still able to reach the senescence phase, the
      cells carrying the genomic imbalance acquired a proliferative advantage, as
      demonstrated by the increase in frequency during long-term culture. CONCLUSIONS:
      Altogether, our results suggest that UC-MSC-based clinical protocols should be
      designed with caution; their clinical use should be preceded by array-comparative
      genomic hybridization screening for the acquisition of genomic imbalances during
      in vitro expansion.

PMID- 24094489
TI  - Co-transplantation of mesenchymal stromal cells and cord blood cells in treatment
      of diabetes.
AB  - BACKGROUND AIMS: Stem cells provide a promising source for treatment of type 1
      diabetes, but the treatment strategy and mechanism remain unclear. The aims of
      this study were to investigate whether co-transplantation of umbilical cord
      derived mesenchymal stromal cells (UC-MSCs) and cord blood mononuclear cells (CB
      MNCs) could reverse hyperglycemia in type 1 diabetic mice and to determine the
      appropriate ratio for co-transplantation. The treatment mechanism was also
      studied. METHODS: A simple and efficient isolation method was developed to
      generate qualified UC-MSCs. UC-MSCs and CB-MNCs were then transplanted into type
      1 diabetic mice at different ratios (UC-MSCs to CB-MNCs = 1:1, 1:4, 1:10) to
      observe the change in blood glucose concentration. Histology,
      immunohistochemistry, and human Alu polymerase chain reaction assay were
      performed to evaluate for the presence of donor-derived cells and the repair of
      endogenous islets. We also induced UC-MSCs into islet-like cells under specific
      culture conditions to determine their differentiate potential in vitro. RESULTS:
      Co-transplantation of UC-MSCs and CB-MNCs at a ratio of 1:4 effectively reversed
      hyperglycemia in diabetic mice. The detection of human Alu sequence indicated
      that the engraftment of donor-derived cells had homed into the recipient's
      pancreas and kidney. Although neither human insulin nor human nuclei antigen was
      detected in the regenerated pancreas, UC-MSCs could differentiate into insulin
      secreted cells in vitro. CONCLUSIONS: Co-transplantation of UC-MSCs and CB-MNCs
      at a ratio of 1:4 could efficiently reverse hyperglycemia and repair pancreatic
      tissue.

PMID- 24094490
TI  - Neuropeptides to replace serum in cryopreservation of mesenchymal stromal cells?
AB  - BACKGROUND AIMS: The therapeutic potential of human mesenchymal stromal cells
      (MSCs) has generated considerable interest in a wide variety of areas. MSC
      banking is feasible, but the optimal technique of cryopreservation remains to be
      determined. METHODS: To reduce dimethyl sulfoxide (DMSO) concentration in
      cryopreservation medium, DMSO was replaced with sucrose or trehalose. To increase
      cell survival and proliferation rates after thawing and to eliminate the need for
      fetal bovine serum (FBS), neuropeptides of the vasoactive intestinal
      peptide/glucose-dependent insulinotropic peptide/pituitary adenylate cyclase
      activating polypeptide family were added to the cryopreservation medium. Cell
      survival was analyzed by a trypan blue dye exclusion assay. Cell proliferation of
      cryopreserved MSCs was determined after 7 days of culture. RESULTS: No
      significant differences in cell survival rates were detected between
      cryopreservation solutions with 5% and 10% DMSO, independently of the addition of
      trehalose or sucrose. Cell proliferation rates tended to be highest when MSCs
      were frozen in 5% DMSO + trehalose. FBS could be replaced by human albumin (HA)
      without loss in cell survival and proliferation potential. With FBS, the addition
      of neuropeptides could increase cell survival and proliferation rates. Without
      FBS or HA, cell survival and proliferation rates in the presence of neuropeptides
      were comparable to rates achieved with FBS or HA. CONCLUSIONS: Classic
      cryopreservation with 10% DMSO could be replaced by 5% DMSO + 30 mmol/L
      trehalose. FBS could be replaced by HA or neuropeptides without loss in cell
      survival and proliferation potential. The addition of neuropeptides in the
      cryopreservation medium containing FBS could increase the cell proliferation rate
      and consequently cellular output.

PMID- 24094491
TI  - Pre-induced adult human peripheral blood mononuclear cells migrate widely into
      the degenerative retinas of rd1 mice.
AB  - BACKGROUND AIMS: Recent advances in stem cell research have raised the
      possibility of stem cells repairing or replacing retinal photoreceptor cells that
      are either dysfunctional or lost in many retinal diseases. Various types of stem
      cells have been used to replace retinal photoreceptor cells. Recently, peripheral
      blood stem cells, a small proportion of pluripotent stem cells, have been
      reported to mainly exist in the peripheral blood mononuclear cells (PBMCs).
      METHODS: In this study, the effects of pre-induced adult human PBMCs (hPBMCs) on
      the degenerative retinas of rd1 mice were investigated. Freshly isolated adult
      hPBMCs were pre-induced with the use of the conditioned medium of rat retinas for
      4 days and were then labeled with chloromethyl-benzamidodialkylcarbocyanine (CM
      DiI) and then transplanted into the subretinal space of the right eye of rd1 mice
      through a trans-scleral approach. The right eyes were collected 30 days after
      transplantation. The survival and migration of the transplanted cells in host
      retinas were investigated by whole-mount retinas, retinal frozen sections and
      immunofluorescent staining. RESULTS: After subretinal transplantation, pre
      induced hPBMCs were able to survive and widely migrate into the retinas of rd1
      mice. A few CM-DiI-labeled cells migrated into the inner nuclear layer and the
      retinal ganglion cell layer. Some transplanted cells in the subretinal space of
      rd1 host mice expressed the human photoreceptor-specific marker rhodopsin.
      CONCLUSIONS: This study suggests that pre-induced hPBMCs may be a potential cell
      source of cell replacement therapy for retinal degenerative diseases.

PMID- 24094493
TI  - Perspective on hormone therapy 10 years after the WHI.
AB  - The Women's Health Initiative (WHI) hormone trials are among the most influential
      and debated research studies in women's health in recent medical history. This
      year (2013) marked the 10th anniversary of the publication of the WHI results and
      this past decade has been nothing less than revolutionary. We have witnessed a
      transformative evolution in our understanding of, and in the practice of,
      menopause management and herein summarize the strides the field has traversed
      over the past 10 years.

PMID- 24094492
TI  - Three specific antigens to isolate endothelial progenitor cells from human
      liposuction material.
AB  - BACKGROUND AIMS: Human endothelial progenitor cells (EPC) play an important role
      in regenerative medicine and contribute to neovascularization on vessel injury.
      They are usually enriched from peripheral blood, cord blood and bone marrow. In
      human fat tissue, EPC are rare and their isolation remains a challenge. METHODS:
      Fat tissue was prepared by collagenase digestion, and the expression of specific
      marker proteins was evaluated by flow cytometry in the stromal vascular fraction
      (SVF). For enrichment, magnetic cell sorting was performed with the use of CD133
      microbeads and EPC were cultured until colonies appeared. A second purification
      was performed with CD34; additional isolation steps were performed with the use
      of a combination of CD34 and CD31 microbeads. Enriched cells were investigated by
      flow cytometry for the expression of endothelial specific markers, by Matrigel
      assay and by the uptake of acetylated low-density lipoprotein. RESULTS: The
      expression pattern confirmed the heterogeneous nature of the SVF, with rare
      numbers of CD133+ detectable. EPC gained from the SVF by magnetic enrichment
      showed cobblestone morphology of outgrowth endothelial cells and expressed the
      specific markers CD31, CD144, vascular endothelial growth factor (VEGF)R2, CD146,
      CD73 and CD105. Functional integrity was confirmed by uptake of acetylated low
      density lipoprotein and the formation of tube-like structures on Matrigel.
      CONCLUSIONS: Rare EPC can be enriched from human fat tissue by magnetic cell
      sorting with the use of a combination of microbeads directed against CD133, an
      early EPC marker, CD34, a stem cell marker, and CD31, a typical marker for
      endothelial cells. In culture, they differentiate into EC and hence could have
      the potential to contribute to neovascularization in regenerative medicine.

PMID- 24094494
TI  - Effects of a 12-wk whole-body vibration based intervention to improve type 2
      diabetes.
AB  - OBJECTIVE: To test the feasibility, safety and effectiveness of a 12-wk whole
      body vibration (WBV) intervention on glycemic control, lipid-related
      cardiovascular risk factors and functional capacity among type 2 diabetes
      mellitus (T2DM) patients in a primary care context. METHODS: Fifty non-insulin
      dependent T2DM patients were randomized 1:1 to an intervention group that, in
      addition to standard care, received a 12-wk WBV intervention, and a control group
      receiving only standard care (from February 2012 through May 2012). Outcomes,
      including glycated hemoglobin (HbA1c), fasting blood glucose, lipid-related
      cardiovascular risk factors (i.e., cholesterol, triglycerides, lipoproteins,
      LDL/HDL and atherogenic index) and functional capacity were measured at baseline
      and after the 12-wk intervention. RESULTS: After intervention, there was a
      reduction in HbA1c and fasting blood glucose when compared to the control group,
      with a mean difference in change scores between groups of -0.55% (95% CI -0.15 to
      -0.76) and -33.95 mm/dl (95% CI -51.38 to -3.47), respectively. Similarly, most
      lipid-related cardiovascular risk factors (i.e., cholesterol, triglycerides and
      atherogenic index) were also reduced (p<0.05). CONCLUSION: A 12-wk WBV
      intervention in a primary care context is feasible, safe and effective in
      improving glycemic profile, lipid-related cardiovascular risk factors and
      functional capacity among T2DM patients. TRIAL NUMBER: ACTRN12613000021774.

PMID- 24094495
TI  - Circadian variation in the pharmacokinetics of steady state continuous
      subcutaneous infusion of growth hormone in adult growth hormone deficient
      patients.
AB  - BACKGROUND: Previous studies in growth hormone (GH)-deficient (GHD) patients have
      indicated a possible diurnal variation in the pharmacokinetics (PK) of GH after
      subcutaneous (sc) GH administration. Thus, higher GH levels were observed during
      the night with continuous sc infusion, and increased GH bioavailability was
      reported following daily sc injections in the evening compared to morning.
      OBJECTIVE: The aim was to study whether diurnal variability in the PK of sc
      administered exogenous GH can be reproduced under standard conditions for all
      study participants, e.g. supine rest. DESIGN AND METHODS: Eight male GHD patients
      (59.8 +/- 8 years, body mass index 29.7 +/- 4.9 kg/m(2)) received a continuous sc
      infusion of GH (3mg/24h) for 60 h on two different occasions. Diurnal variation
      in PK of GH was studied during steady state in the last 24h of the infusion
      period. RESULTS: Median GH levels were higher at night time (23:00 h-07:00 h)
      than during the day (10:00 h-18:00 h) for visit 1 [5.1 (4.5-7.2 ng/ml/0.5h) vs.
      4.6 (3.7-5.7 ng/ml/0.5h); p<0.05], and reproducible results of diurnal GH
      variation were obtained during visit 2 [5.7 (4.6-7.4) ng/ml/0.5h vs. 4.6 (3.8
      6.0) ng/ml/0.5h, p<0.05]. Reproducible results between days 1 and 2 were also
      obtained during 08:30 h-20:30 h and 20:30 h-08:30 h, respectively. CONCLUSIONS:
      Previous findings of higher nocturnal GH levels were confirmed during steady
      state continuous sc GH infusion under standard conditions. The underlying
      mechanisms, e.g. whether GH absorption, distribution or elimination is primarily
      affected need to be further elucidated.

PMID- 24094496
TI  - Treatment of patients with advanced cancer with the natural killer cell line NK
      92.
AB  - BACKGROUND AIMS: Natural killer (NK) cells, either naive or genetically
      engineered, are increasingly considered for cellular therapy of patients with
      malignancies. When using NK cells from peripheral blood, the number of expanded
      NK cells can be highly variable and the need for NK cell enrichment can make the
      process expensive. The NK-92 cell line (CD56+/CD3-) that was isolated from a
      patient with lymphoma has predictable high cytotoxic activity and can be expanded
      under good manufacturing practice conditions in recombinant interleukin-2.
      METHODS: Fifteen patients (age, 9-71 years) with advanced, treatment-resistant
      malignancies, either solid tumors/sarcomas (n = 13) or leukemia/lymphoma (n = 2),
      received two infusions of NK-92 cells, given 48 h apart. Three cohorts of
      patients were treated with escalating doses of NK-92 cells (n = 7 at 1 * 10(9), n
      = 6 at 3 * 10(9) and n = 2 at 1 * 10(10) cells/m(2)). RESULTS: No infusion
      related or long-term side effects were observed. The dose of 10(10) cells/m(2)
      was considered the maximum expandable cell dose with the use of an established
      culture bag system. Three fourths of patients with lung cancer had some anti
      tumor response. Only one patient of seven had development of human leukocyte
      antigen antibodies. The persistence of NK-92 cells (male origin) in the
      circulation was confirmed by Y chromosome-specific polymerase chain reaction in
      two female patients. CONCLUSIONS: Infusions of NK-92 cells up to 10(10)
      cells/m(2) were well tolerated. Despite the allogeneic nature of NK-92,
      development of human leukocyte antigen antibodies in these patients with cancer
      appears to be rare. The cells can persist in the recipient's circulation for at
      least 48 h. Some encouraging responses were seen in patients with advanced lung
      cancer.

PMID- 24094497
TI  - Fucosylation with fucosyltransferase VI or fucosyltransferase VII improves cord
      blood engraftment.
AB  - BACKGROUND AIMS: Advantages associated with the use of cord blood (CB)
      transplantation include the availability of cryopreserved units, ethnic diversity
      and lower incidence of graft-versus-host disease compared with bone marrow or
      mobilized peripheral blood. However, poor engraftment remains a major obstacle.
      We and others have found that ex vivo fucosylation can enhance engraftment in
      murine models, and now ex vivo treatment of CB with fucosyltransferase (FT) VI
      before transplantation is under clinical evaluation (NCT01471067). However, FTVII
      appears to be more relevant to hematopoietic cells and may alter acceptor
      substrate diversity. The present study compared the ability of FTVI and FTVII to
      improve the rapidity, magnitude, multi-lineage and multi-tissue engraftment of
      human CB hematopoietic stem and progenitor cells (HSPCs) in vivo. METHODS: CD34
      selected CB HSPCs were treated with recombinant FTVI, FTVII or mock control and
      then injected into immunodeficient mice and monitored for multi-lineage and multi
      tissue engraftment. RESULTS: Both FTVI and FTVII fucosylated CB CD34+ cells in
      vitro, and both led to enhanced rates and magnitudes of engraftment compared with
      untreated CB CD34+ cells in vivo. Engraftment after treatment with either FT was
      robust at multiple time points and in multiple tissues with similar multi-lineage
      potential. In contrast, only FTVII was able to fucosylate T and B lymphocytes.
      CONCLUSIONS: Although FTVI and FTVII were found to be similarly able to
      fucosylate and enhance the engraftment of CB CD34+ cells, differences in their
      ability to fucosylate lymphocytes may modulate graft-versus-tumor or graft-versus
      host effects and may allow further optimization of CB transplantation.

PMID- 24094499
TI  - Immunosuppressive properties of mesenchymal stromal cell cultures derived from
      the limbus of human and rabbit corneas.
AB  - BACKGROUND AIMS: Mesenchymal stromal cells (MSCs) cultivated from the corneal
      limbus (L-MSCs) provide a potential source of cells for corneal repair. In the
      present study, we investigated the immunosuppressive properties of human L-MSCs
      and putative rabbit L-MSCs to develop an allogeneic therapy and animal model of L
      MSC transplantation. METHODS: MSC-like cultures were established from the limbal
      stroma of human and rabbit (New Zealand white) corneas using either serum
      supplemented medium or a commercial serum-free MSC medium (MesenCult-XF Culture
      Kit; Stem Cell Technologies, Melbourne, Australia). L-MSC phenotype was examined
      by flow cytometry. The immunosuppressive properties of L-MSC cultures were
      assessed using mixed leukocyte reactions. L-MSC cultures were also tested for
      their ability to support colony formation by primary limbal epithelial (LE)
      cells. RESULTS: Human L-MSC cultures were typically CD34-, CD45- and HLA-DR- and
      CD73+, CD90+, CD105+ and HLA-ABC+. High levels (>80%) of CD146 expression were
      observed for L-MSC cultures grown in serum-supplemented medium but not cultures
      grown in MesenCult-XF (approximately 1%). Rabbit L-MSCs were approximately 95%
      positive for major histocompatibility complex class I and expressed lower levels
      of major histocompatibility complex class II (approximately 10%), CD45
      (approximately 20%), CD105 (approximately 60%) and CD90 (<10%). Human L-MSCs and
      rabbit L-MSCs suppressed human T-cell proliferation by up to 75%. Conversely, L
      MSCs from either species stimulated a 2-fold to 3-fold increase in LE cell colony
      formation. CONCLUSIONS: L-MSCs display immunosuppressive qualities in addition to
      their established non-immunogenic profile and stimulate LE cell growth in vitro
      across species boundaries. These results support the potential use of allogeneic
      L-MSCs in the treatment of corneal disorders and suggest that the rabbit would
      provide a useful pre-clinical model.

PMID- 24094498
TI  - Combination of Epstein-Barr virus nuclear antigen 1, 3 and lytic antigen BZLF1
      peptide pools allows fast and efficient stimulation of Epstein-Barr virus
      specific T cells for adoptive immunotherapy.
AB  - BACKGROUND: Epstein-Barr virus (EBV) infection is a major cause of morbidity
      following hematopoietic stem cell transplantation. EBV-infected B cells may not
      respond to rituximab treatment and may lead to a life-threatening post
      transplantation lymphoproliferative disorder. Adoptive cellular immunotherapy
      using EBV-lymphoblastoid cell lines (LCL) as stimulating antigen has proved
      effective in restoring specific immunity. However, EBV presents several
      immunodominant antigens, and developing a swift and effective clinical-grade
      immunotherapy relies on the definition of a Good Manufacturing Practices (GMP)
      universal stimulating antigen. METHODS: Peripheral blood mononuclear cells
      (PBMCs) from six donors with a cellular immune response against EBV were
      immunoselected after stimulation with a new EBV antigen associated with an EBNA3
      peptide pool. RESULTS: After immunoselection, a mean of 0.53 +/- 0.25 * 106 cells
      was recovered consisting of a mean of 24.77 +/- 18.01% CD4+-secreting interferon
      (IFN)-gamma and 51.42 +/- 26.92% CD8+-secreting IFN-gamma. The T memory stem cell
      sub-population was identified. EBV-specific T cells were expanded in vitro, and
      their ability to secrete IFN-gamma and to proliferate after re-stimulation with
      EBV antigen was confirmed. A specific lysis was observed against autologous
      target cells pulsed with EBV peptide pools (57.6 +/- 11.5%) and against
      autologous EBV-LCL (18.3 +/- 7.3%). A mean decrease of 94.7 +/- 3.3% in
      alloreactivity against third-party donor mononuclear cells with EBV-specific T
      cells was observed compared with PBMCs before selection. CONCLUSIONS: Our results
      show that a combination of peptide pools including EBNA3 is needed to generate
      EBV-specific T cells with good specific cytotoxicity and devoid of
      alloreactivity, but as yet GMP grade is not fully achieved.

PMID- 24094500
TI  - Conditioned medium from amniotic membrane-derived cells prevents lung fibrosis
      and preserves blood gas exchanges in bleomycin-injured mice-specificity of the
      effects and insights into possible mechanisms.
AB  - BACKGROUND AND AIMS: We recently demonstrated that injection of conditioned
      medium (CM) generated from cells of the mesenchymal region of human amniotic
      membrane (AMTCs) reduces bleomycin-induced lung fibrosis in mice, suggesting a
      crucial role of paracrine factor(s) secreted by AMTCs in these beneficial
      effects. We further investigated this hypothesis, the mechanisms involved, the
      effects on some lung functional parameters and whether AMTC-secreted effector(s)
      are specific to these cells and not produced by other cell types, extending the
      time of analysis up to 28 days after treatment. METHODS: Bleomycin-challenged
      mice were either treated with AMTC-CM or CM generated from human skin
      fibroblasts, human peripheral blood mononuclear cells or Jurkat cells, or were
      left untreated. Mouse lungs were analyzed for content of pro-inflammatory and pro
      fibrotic molecules, presence of lymphocytes and macrophages and for fibrosis
      level (through histological semi-quantitative evaluation and quantitative
      measurement of collagen content). Arterial blood gas analysis was also performed.
      RESULTS: Up to 28 days after delivery, AMTC-CM-treated mice developed reduced
      lung fibrosis with respect to mice treated with other CM types. AMTC-CM-treated
      mice had comparatively better preservation of blood gas parameters and showed
      lower lung content of interleukin-6, tumor necrosis factor-alpha, macrophage
      inflammatory protein-1alpha, monocyte chemoattractant protein-1 and transforming
      growth factor-beta associated with reduced lung macrophage levels. CONCLUSIONS:
      AMTC-CM prevents lung fibrosis in bleomycin-challenged mice, improving survival
      and preserving lung functional parameters such as blood gas exchanges. The
      specificity of AMTC-CM action was indicated by the absence of fibrosis reduction
      when other CM types were used. Finally, we provide some insights into the
      possible mechanisms underlying AMTC-CM-mediated control of fibrosis.

PMID- 24094501
TI  - The trend of macrolide resistance and emm types of group A streptococci from
      children at a medical center in southern Taiwan.
AB  - BACKGROUND: Group A streptococcus (GAS) is a common pathogen in children.
      Macrolide resistance in GAS has been described worldwide. The aims of this study
      are to analyze macrolide resistance of GAS isolates in southern Taiwan and to
      clarify the relationship of emm typing and macrolide resistance in the past
      decade. METHODS: All GAS isolated from patients younger than 18 years at a single
      tertiary center in southern Taiwan were collected from 2000 to 2012. Antibiotics
      susceptibility to erythromycin, azithromycin, and clindamycin were determined by
      agar dilution method, and were interpreted by Clinical and Laboratory Standards
      Institute (CLSI) standards. emm typing was performed by polymerase chain reaction
      (PCR). RESULTS: A total of 301 isolates were collected during the period of 13
      years. Scarlet fever (38.5%) and acute pharyngitis (32.2%) were the most common
      diagnosis. Decreased resistance rate of erythromycin from 53.1% in 2000 to 0% in
      2010 was found, but it increased rapidly to 65% in 2011. The resistance rate of
      azithromycin was the lowest (4.2%) in 2005, but was higher than 15% after 2006.
      The involvement of the erythromycin resistance genes were mefA (53.1%), ermB
      (35.9%), and ermTR (10.9%). The resistance of clindamycin also increased since
      2011. emm12 was the most common serotype and accounted for 44.9% of all isolates.
      Compared with the non-emm12 group, resistance to erythromycin, azithromycin, and
      clindamycin were more frequently detected in the emm12 group. CONCLUSION:
      Increased resistance of GAS to macrolide and clindamycin was found in recent
      years. emm12 was the main serotype for macrolide resistance.

PMID- 24094502
TI  - Pyogenic liver abscess among children in a medical center in Central Taiwan.
AB  - BACKGROUND: Pediatric pyogenic liver abscess is uncommon. This study aimed to
      investigate the clinical characteristics, radiologic features, pathogens,
      duration of hospitalization, and management of pediatric pyogenic liver abscess.
      METHODS: Pediatric patients with pyogenic liver abscess admitted to the China
      Medical University Hospital from 1995 to 2011 were reviewed. Their clinical
      characteristics, radiological features, laboratory data, clinical management, and
      outcomes were analyzed. Those with liver abscess due to the complication of
      oncologic disease were excluded. RESULTS: Fifteen patients were diagnosed with
      pyogenic liver abscess. Their most common symptoms were fever and abdominal pain.
      Eight (53.0%) had leukocytosis (>15000/MUL) and elevated C-reactive protein (CRP)
      level (>10 mg/dL). The main imaging presentation was a single abscess in right
      lobe of the liver (13/15, 86.7%). Blood culture were mainly negative (12/15,
      80.0%). Pathogenic microorganisms cultured from pus revealed Klebsiella
      pneumoniae (6/15, 40.0%) and Streptococcus spp. (6/15, 40.0%) as the two most
      common pathogens. Percutaneous abscess drainage followed by adequate parenteral
      antibiotics were effective interventions. Hospitalization of at least 2 weeks was
      needed in most cases. There were no mortalities. CONCLUSION: Pyogenic liver
      abscess should be considered in children presenting with fever, abdominal pain,
      and leukocytosis with a high CRP level. Most cases involve a single lesion on
      right lobe of the liver. K. pneumoniae and Streptococcus spp. are the two most
      common pathogens. Drainage with adequate antibiotics has significantly good
      response.

PMID- 24094503
TI  - [A history and review of cholesterol ester transfer protein inhibitors and their
      contribution to the understanding of the physiology and pathophysiology of high
      density lipoprotein].
AB  - There is irrefutable evidence that statins reduce the risk of cardiovascular
      events in a magnitude proportional to the intensity of the decrease in
      cholesterol transport by the low density lipoproteins. Despite this great advance
      there is still a residual risk of cardiovascular events. For this reason, an
      increase in the levels of high density lipoprotein is considered in order to
      boost the main action of this lipoprotein, which is reverse cholesterol
      transport. Distinct classes of evidence (epidemiological, genetic, and
      pathophysiological) show that the inhibition and/or modulation of cholesterol
      ester transfer protein increases plasma high density lipoprotein-cholesterol
      levels. The main reason for presenting this review is to look at the physiology
      of cholesterol ester transfer protein, its interrelationship with high density
      lipoproteins, and to give an update on the development of different cholesterol
      ester transfer protein inhibitor/modulator molecules. 

PMID- 24094504
TI  - [Bitemporal hemianopia as presenting sign of severe ethambutol toxicity].
AB  - INTRODUCTION: Optic neuropathy is a severe and well-known complication of
      ethambutol treatment. If not detected early, it may lead to profound and
      irreversible vision loss. CASE REPORT: We report the case of a 83-year-old female
      patient, referred for rapidly progressive, painless, bilateral visual loss,
      unimproved after bilateral cataract surgery. Automated Humphrey 24-2 visual field
      demonstrated bitemporal hemianopia associated with bilateral central scotoma.
      Brain MRI did not demonstrate any compressive lesion in the chiasmal region.
      However, on T2-weighted sequences, an area of elevated signal intensity appeared
      within the optic chiasm, enhancing after gadolinium injection. On detailed
      history, it was noted that the patient had been on ethambutol for the last
      18months, for the treatment of a Mycobacterium avium-related pneumonitis.
      DISCUSSION: The incidence of ethambutol-related toxic optic neuropathy has
      dramatically decreased since the recommendations for regular follow-up of
      patients treated with ethambutol. This treatment is classically responsible for
      bilateral central or ceco-central scotoma due to optic neuropathy, although a few
      cases of bitemporal hemianopia have been reported in the literature, mimicking a
      compressive chiasmal lesion. However, none of these cases demonstrated a
      hypersignal in the optic chiasm on brain magnetic resonance imaging (MRI).
      CONCLUSION: Bitemporal hemianopia on visual field testing is very suggestive of a
      chiasmal lesion, which is generally due to a compressive, or more rarely
      inflammatory, lesion in the sellar region. Toxic chiasmal lesions are rare, but
      in the absence of any tumoral lesion in the sellar area, a detailed history must
      be obtained in order to rule out drug toxicity, so as to prevent irreversible
      visual loss.

PMID- 24094505
TI  - Orbital cysticercosis and third nerve palsy.

PMID- 24094506
TI  - [Clinical and microbiological features of severe infectious keratitis during
      heatwaves].
AB  - PURPOSE: To study clinical and microbiological features of patients with severe
      microbial keratitis during a heatwave. To evaluate the links between disease
      severity, causative micro-organisms and temperature variation. METHODS:
      Retrospective study of patients with microbial keratitis hospitalized in a
      referral center during the summer months (between June 1, 2009 and September 30,
      2009), separated into two groups by date of hospitalization (heatwave vs non
      heatwave). Prevalence and daytime temperatures were compared for data collected
      during the summers of 2009 (heatwave), 2008 (temperate) and 2003 (prolonged
      heatwave). RESULTS: Thirty-three patients were hospitalized during the summer of
      2009, with an average age of 51 years and an average stay of 15 days. The primary
      predisposing factor was the use of contact lenses (36%), followed by pre-existing
      corneal disease (15%) and systemic disease (15%). Prevalence of severe keratitis
      was higher in periods of heatwaves vs periods of no heatwaves (mean 9.8 patients
      vs 3.1, P<0.001). Best corrected visual acuity progressed from 1/30 at admission
      to 1/10 at 1 month after discharge (P<0.001). The most common bacteria identified
      were Gram-positive cocci (CNS 27%) and Pseudomonas (23%). Microbiological results
      were similar in the two groups. Similar variations between the prevalence of
      severe keratitis and daytime temperatures were found for the summer of 2009 as
      well as for the summers of 2008 and 2003. CONCLUSIONS: There appears to be a link
      between climatic temperature variations and the prevalence of severe microbial
      keratitis.

PMID- 24094507
TI  - A simple nonlinear PD controller for integrating processes.
AB  - Many industrial processes are found to be integrating in nature, for which widely
      used Ziegler-Nichols tuned PID controllers usually fail to provide satisfactory
      performance due to excessive overshoot with large settling time. Although, IMC
      (Internal Model Control) based PID controllers are capable to reduce the
      overshoot, but little improvement is found in the load disturbance response.
      Here, we propose an auto-tuning proportional-derivative controller (APD) where a
      nonlinear gain updating factor alpha continuously adjusts the proportional and
      derivative gains to achieve an overall improved performance during set point
      change as well as load disturbance. The value of alpha is obtained by a simple
      relation based on the instantaneous values of normalized error (eN) and change of
      error (DeltaeN) of the controlled variable. Performance of the proposed nonlinear
      PD controller (APD) is tested and compared with other PD and PID tuning rules for
      pure integrating plus delay (IPD) and first-order integrating plus delay (FOIPD)
      processes. Effectiveness of the proposed scheme is verified on a laboratory scale
      servo position control system. 

PMID- 24094508
TI  - Rare nonsynonymous exonic variants in addiction and behavioral disinhibition.
AB  - BACKGROUND: Substance use is heritable, but few common genetic variants have been
      associated with these behaviors. Rare nonsynonymous exonic variants can now be
      efficiently genotyped, allowing exome-wide association tests. We identified and
      tested 111,592 nonsynonymous exonic variants for association with behavioral
      disinhibition and the use/misuse of nicotine, alcohol, and illicit drugs.
      METHODS: Comprehensive genotyping of exonic variation combined with single
      variant and gene-based tests of association was conducted in 7181 individuals;
      172 candidate addiction genes were evaluated in greater detail. We also evaluated
      the aggregate effects of nonsynonymous variants on these phenotypes using Genome
      wide Complex Trait Analysis. RESULTS: No variant or gene was significantly
      associated with any phenotype. No association was found for any of the 172
      candidate genes, even at reduced significance thresholds. All nonsynonymous
      variants jointly accounted for 35% of the heritability in illicit drug use and,
      when combined with common variants from a genome-wide array, accounted for 84% of
      the heritability. CONCLUSIONS: Rare nonsynonymous variants may be important in
      etiology of illicit drug use, but detection of individual variants will require
      very large samples.

PMID- 24094509
TI  - The dyslexia-associated gene DCDC2 is required for spike-timing precision in
      mouse neocortex.
AB  - BACKGROUND: Variants in dyslexia-associated genes, including DCDC2, have been
      linked to altered neocortical activation, suggesting that dyslexia associated
      genes might play as yet unspecified roles in neuronal physiology. METHODS: Whole
      cell patch clamp recordings were used to compare the electrophysiological
      properties of regular spiking pyramidal neurons of neocortex in Dcdc2 knockout
      (KO) and wild-type mice. Ribonucleic acid sequencing and reverse transcriptase
      polymerase chain reaction were performed to identify and characterize changes in
      gene expression in Dcdc2 KOs. RESULTS: Neurons in KOs showed increased
      excitability and decreased temporal precision in action potential firing. The RNA
      sequencing screen revealed that the N-methyl-D-aspartate receptor (NMDAR) subunit
      Grin2B was elevated in Dcdc2 KOs, and an electrophysiological assessment
      confirmed a functional increase in spontaneous NMDAR-mediated activity.
      Remarkably, the decreased action potential temporal precision could be restored
      in mutants by treatment with either the NMDAR antagonist (2R)-amino-5
      phosphonovaleric acid or the NMDAR 2B subunit-specific antagonist Ro 25-6981.
      CONCLUSIONS: These results link the function of the dyslexia-associated gene
      Dcdc2 to spike timing through activity of NMDAR.

PMID- 24094511
TI  - Maternal-preterm skin-to-skin contact enhances child physiologic organization and
      cognitive control across the first 10 years of life.
AB  - BACKGROUND: Maternal-newborn contact enhances organization of the infant's
      physiological systems, including stress reactivity, autonomic functioning, and
      sleep patterns, and supports maturation of the prefrontal cortex and its ensuing
      effects on cognitive and behavioral control. Premature birth disrupts brain
      development and is associated with maternal separation and disturbances of
      contact-sensitive systems. However, it is unknown whether the provision of
      maternal-preterm contact can improve long-term functioning of these systems.
      METHODS: We used the Kangaroo Care (KC) intervention and provided maternal
      newborn skin-to-skin contact to 73 premature infants for 14 consecutive days
      compared with 73 case-matched control subjects receiving standard incubator care.
      Children were then followed seven times across the first decade of life and
      multiple physiologic, cognitive, parental mental health, and mother-child
      relational measures were assessed. RESULTS: KC increased autonomic functioning
      (respiratory sinus arrhythmia, RSA) and maternal attachment behavior in the
      postpartum period, reduced maternal anxiety, and enhanced child cognitive
      development and executive functions from 6 months to 10 years. By 10 years of
      age, children receiving KC showed attenuated stress response, improved RSA,
      organized sleep, and better cognitive control. RSA and maternal behavior were
      dynamically interrelated over time, leading to improved physiology, executive
      functions, and mother-child reciprocity at 10 years. CONCLUSIONS: These findings
      are the first to demonstrate long-term effects of early touch-based intervention
      on children's physiologic organization and behavioral control and have salient
      implications for the care practices of premature infants. Results demonstrate the
      dynamic cascades of child physiological regulation and parental provisions in
      shaping developmental outcome and may inform the construction of more targeted
      early interventions.

PMID- 24094510
TI  - Angiotensin type 1 receptor inhibition enhances the extinction of fear memory.
AB  - BACKGROUND: The current effective treatment options for posttraumatic stress
      disorder (PTSD) are limited, and therefore the need to explore new treatment
      strategies is critical. Pharmacological inhibition of the renin-angiotensin
      system is a common approach to treat hypertension, and emerging evidence
      highlights the importance of this pathway in stress and anxiety. A recent
      clinical study from our laboratory provides evidence supporting a role for the
      renin-angiotensin system in the regulation of the stress response in patients
      diagnosed with PTSD. METHODS: With an animal model of PTSD and the selective
      angiotensin receptor type 1 (AT1) antagonist losartan, we investigated the acute
      and long-term effects of AT1 receptor inhibition on fear memory and baseline
      anxiety. After losartan treatment, we performed classical Pavlovian fear
      conditioning pairing auditory cues with footshocks and examined extinction
      behavior, gene expression changes in the brain, as well as neuroendocrine and
      cardiovascular responses. RESULTS: After cued fear conditioning, both acute and 2
      week administration of losartan enhanced the consolidation of extinction memory
      but had no effect on fear acquisition, baseline anxiety, blood pressure, and
      neuroendocrine stress measures. Gene expression changes in the brain were also
      altered in mice treated with losartan for 2 weeks, in particular reduced amygdala
      AT1 receptor and bed nucleus of the stria terminalis c-Fos messenger RNA levels.
      CONCLUSIONS: These data suggest that AT1 receptor antagonism enhances the
      extinction of fear memory and therefore might be a beneficial therapy for PTSD
      patients who have impairments in extinction of aversive memories.

PMID- 24094512
TI  - A selective role for dopamine D4 receptors in modulating reward expectancy in a
      rodent slot machine task.
AB  - BACKGROUND: Cognitive distortions regarding gambling outcomes confer
      vulnerability to pathological gambling. Using a rat slot machine task (rSMT), we
      previously demonstrated that the nonspecific D2 agonist quinpirole enhances
      erroneous expectations of reward on near-miss trials, suggesting a pivotal role
      for the D2 receptor family in mediating the near-miss effect. Identifying which
      receptor subtype is involved could facilitate treatment development for
      compulsive slot machine play. METHODS: Thirty-two male Long Evans rats learned
      the rSMT. Three flashing lights could be set to on or off. A win was signaled if
      all three lights were set to on, whereas any other light pattern indicated a
      loss. Rats then chose between responding on the collect lever, which delivered 10
      sugar pellets on win trials but a 10-second time penalty on loss trials, or to
      start a new trial instead. Performance was assessed following systemic
      administration of selective D2, D3, and D4 receptor ligands. RESULTS: The
      selective D2 antagonist L-741,626, the D3 antagonist SB-277011-A, and the D3
      agonist PD128,907 had no effect. In contrast, the selective D4 agonist PD168077
      partially mimicked quinpirole's effects, increasing erroneous collect responses
      on nonwin trials, whereas the D4 antagonist L-745,870 improved the error rate. L
      745,870 was also the only antagonist that could attenuate the deleterious effects
      of quinpirole. CONCLUSIONS: The dopamine D4 receptor is critically involved in
      signaling reward expectancy in the rSMT. The ability of L-745,870 to reduce the
      classification of losses as wins suggests that D4 antagonists could be effective
      in treating problematic slot machine play.

PMID- 24094514
TI  - Orthosis or orthotic: which is it when?

PMID- 24094515
TI  - Biosimilars and reference biologics: decisions on biosimilar interchangeability
      require the involvement of dermatologists.

PMID- 24094513
TI  - Neuroimaging biomarkers for early drug development in schizophrenia.
AB  - Given the relative inability of currently available antipsychotic treatments to
      adequately provide sustained recovery and improve quality of life for patients
      with schizophrenia, new treatment strategies are urgently needed. One way to
      improve the therapeutic development process may be an increased use of biomarkers
      in early clinical trials. Reliable biomarkers that reflect aspects of disease
      pathophysiology can be used to determine if potential treatment strategies are
      engaging their desired biological targets. This review evaluates three potential
      neuroimaging biomarkers: hippocampal hyperactivity, gamma-band deficits, and
      default network abnormalities. These deficits have been widely replicated in the
      illness, correlate with measures of positive symptoms, are consistent with models
      of disease pathology, and have shown initial promise as biomarkers of biological
      response in early studies of potential treatment strategies. Two key features of
      these deficits, and a guiding rationale for the focus of this review, are that
      the deficits are not dependent upon patients' performance of specific cognitive
      tasks and they have analogues in animal models of schizophrenia, greatly
      increasing their appeal for use as biomarkers. Using neuroimaging biomarkers such
      as those proposed here to establish early in the therapeutic development process
      if treatment strategies are having their intended biological effect in humans may
      facilitate development of new treatments for schizophrenia. 

PMID- 24094516
TI  - Biologic therapies for moderate to severe psoriasis are not interchangeable.
AB  - Health care managers and hospital pharmacists are increasingly compelling
      prescribers to use medication substitutes. This policy becomes particularly
      evident when the agents are biologics with shared indications based on their
      assumed clinical equivalence and efficiency (cost-effectiveness), and in these
      cases the involvement of clinicians in decision making is often minimal or
      nonexistent. Lacking head-to-head clinical trials comparing various drugs, the
      prescriber can use indirect comparisons to define 2 or more agents as clinically
      equivalent therapeutic alternatives. This denomination of clinical equivalence
      does not imply that 2 such medications are truly therapeutically equivalent, or
      therapeutic equivalents, as this type of equivalence is defined by the absence of
      statistically significant differences between the drugs on all measures of effect
      in most patients, meaning that neither one is preferable to the other in
      different situations. Although real patients are not entirely comparable to those
      in clinical trials, the choice of a biologic agent to treat psoriasis is largely
      based on the findings of such trials. A recently published meta-analysis shows
      that not all the biologics currently available to treat moderate to severe
      psoriasis can be considered therapeutic equivalents, in spite of the authors'
      claim to the contrary; indeed, infliximab and etanercept can in no way be
      considered equivalent therapeutic alternatives based on the data provided.
      Biologics do display real differences with respect to efficacy at different time
      points and in the time required to onset of effect. In any case, therapeutic
      decisions should be made by an experienced clinician and tailored to each
      individual patient. 

PMID- 24094517
TI  - Medical emergencies and cardiopulmonary arrests in interventional radiology.
AB  - PURPOSE: To evaluate the circumstances and determine the outcomes of medical
      emergencies (MEs) and cardiopulmonary arrests (CPAs) in patients undergoing
      interventional radiology (IR) procedures. MATERIALS AND METHODS: Retrospective
      review of all MEs and CPAs that occurred between July 2006 and December 2011 was
      performed. Procedure type, technical outcome, complications, etiology and
      location of ME/CPA, event outcome, and postevent mortality were collected.
      RESULTS: A total of 58 events occurred during 38,927 procedures (0.15%). Complete
      records were available for 55 events (43 MEs, 12 CPAs) in 53 patients (mean age,
      63 y; 58.5% male) during 37 inpatient (27 MEs, 10 CPAs) and 18 outpatient (16
      MEs, two CPAs) encounters. Seven events (13%; six MEs, one CPA) occurred before
      the start of the procedure, and 18 (33%; 16 MEs, two CPAs) occurred in the
      periprocedural holding area. Thirty-five procedures (64%) were completed
      successfully. Forty-two patients (76%) were alive at discharge, 37 (67%) at 1
      month, 26 (47%) at 3 months, and 23 (42%) at 1 year. Procedural complications
      were attributed as the main cause of 22 MEs (51%) and one CPA (8%; P = .018). The
      relative risk (RR) of an ME or CPA occurring during a hemodialysis access case
      versus all other cases was 5.2 (95% confidence interval = 3.02-8.95; P < .0001).
      CONCLUSIONS: Although the incidence of MEs/CPAs in patients undergoing IR
      procedures is low, the 1-year mortality rate following these events is high. MEs
      are significantly more likely than CPAs to be directly attributed to a procedural
      complication. The RR of MEs/CPAs is significantly higher in hemodialysis access
      interventions.

PMID- 24094518
TI  - Video-assisted thoracic surgery for pulmonary aspergilloma: a safe and effective
      procedure.
AB  - BACKGROUND: A variety of complications occur in patients with pulmonary
      aspergilloma. The safety and feasibility of a thoracoscopic approach to
      therapeutic lung resection for pulmonary aspergilloma have not been well
      evaluated. METHODS: The medical records of patients who underwent video-assisted
      thoracic surgery (VATS) or a thoracotomy for therapeutic resection of pulmonary
      aspergilloma between January 2005 and December 2012 were retrospectively reviewed
      for age, sex, indications for surgery, approach and procedures, postoperative
      pain, operative time, blood loss, hospital stay, cost, and complications.
      RESULTS: A total of 310 patients underwent thoracotomy, 76 patients underwent
      attempted VATS lobectomy. Seventy-six patients from 310 patients for thoracotomy
      were selected and compared with the VATS group. Nine cases (11.8%) in the VATS
      group were converted to a thoracotomy for the following reasons: bleeding (n =2);
      dense fibrous adhesions (n =3); fused interlobar fissure (n =2); and hilar
      lymphadenopathy (n = 2). Lesions treated with pneumonectomy failed to be done
      using VATS. There was no difference in the blood loss and median operative time
      between the 2 groups, but the patients with VATS had shorter length of stay in
      the hospital (p = 0.035) and fewer complications (p = 0.032) than those with
      thoracotomy. CONCLUSIONS: Video-assisted thoracic surgery is an alternative to
      open procedures in the management of pulmonary aspergilloma. Simple aspergilloma
      and complex aspergilloma without infiltration of the hilum are good candidates
      for VATS resection. Aspergilloma lesions that require a pneumonectomy are still a
      major challenge for VATS.

PMID- 24094519
TI  - Osteopontin combined with CD44v6, a novel prognostic biomarker in non-small cell
      lung cancer undergoing curative resection.
AB  - BACKGROUND: Osteopontin (OPN) is identified as one of the leading genes that
      promote the metastasis of malignant tumor through binding to CD44v6 and integrin.
      The purpose of the current study was to assess the prognostic significance of OPN
      and CD44v6 in patients with non-small cell lung cancer (NSCLC). METHODS: Tissue
      microarray was used to detect the expression of OPN and CD44v6 in 159 NSCLC
      patients undergoing complete pulmonary resection in our hospital between 2003 and
      2006. The correlations among OPN, CD44v6, and clinicopathologic data were
      analyzed using chi(2) testing analysis. The prognostic values of OPN and CD44v6
      were evaluated by univariate Kaplan-Meier survival analysis and multivariate Cox
      proportional hazard model analysis. RESULTS: OPN and CD44v6 were both independent
      predictors for overall survival and disease-free survival. When OPN and CD44v6
      were considered together, the predictive range was extended and the sensitivity
      was improved, especially for those patients with stage I NSCLC. The 6-year
      overall survival and disease-free survival rates in OPN+ or CD44v6+ patients were
      49.1% and 39.6%, respectively, which were significantly lower than those of OPN
      /CD44v6- patients (64.4% and 47.7%, respectively), and were higher than those of
      OPN+/CD44v6+ patients (16.4% and 14.8%, respectively). Stratification into
      OPN+/CD44v6+, OPN+ or CD44v6+, or OPN-/CD44v6- groups, based on the expression
      OPN and CD44v6, could efficiently predicted outcomes (p < 0.001) of NSCLC
      patients. CONCLUSIONS: The combination of OPN and CD44v6 is a valuable
      independent predictor of tumor recurrence and survival in NSCLC patients.

PMID- 24094520
TI  - Prognostic factors associated with interventional bronchoscopy in lung cancer.
AB  - BACKGROUND: Interventional bronchoscopy is an effective procedure for malignant
      central airway obstruction, although its indications are poorly defined and its
      benefits difficult to predict. The purpose of the study was to identify the
      patients' or the disease's characteristics that are correlated with survival to
      enable clinicians to identify the best indications. METHODS: We retrospectively
      studied the data from 204 patients treated between 2004 and 2010. We analyzed
      survival times according to the patients' or disease's characteristics, and
      identified homogeneous risks using classification and regression trees. RESULTS:
      Reduced survival was associated with a high American Society of Anesthesiologists
      score (13, 5.9, and 2.9 months for scores of 2, 3, and 4, respectively; p =
      0.0005), nonsquamous cell histology (median survival, 6.3 months; p = 0.007),
      metastatic tumors (9.2 and 6.2 months for stage IIIA and IIIB, respectively,
      versus 3 months for stage IV; p = 0.0002), and for patients who had not received
      a specific treatment (median survival, 8.6 versus 3.2 months for untreated
      patients; p < 0.0001). Classification and regression trees segmentation
      identified five distinct groups of patients. Patients receiving a specific
      treatment for squamous cell carcinoma derived the best survival (median, 13
      months; p < 0.0001), whereas patients with an American Society of
      Anesthesiologists score of 4 treated for large cell cancer or adenocarcinoma and
      metastatic patients who did not receive any specific treatment had the worst
      survival (0.8 months and 2.7 months, respectively; p < 0.0001). CONCLUSIONS:
      Interventional bronchoscopy is a safe and effective procedure that should be
      integrated into a multimodal therapy for selected patients.

PMID- 24094521
TI  - Transfusion of 1 and 2 units of red blood cells is associated with increased
      morbidity and mortality.
AB  - BACKGROUND: This study examined the relationship between transfusion of 1 or 2
      units of red blood cells (RBCs) and the risk of morbidity and mortality after
      isolated on-pump coronary artery bypass grafting (CABG). METHODS: A total of
      22,785 consecutive patients underwent isolated on-pump CABG between January 1,
      2008, and December 31, 2011 in Michigan. We excluded 5,950 patients who received
      three or more RBC units. Twenty-one preoperative variables significantly
      associated with transfusion by univariate analysis were included in a logistic
      regression model predicting transfusion, and propensity scores were calculated.
      Transfusion and the propensity score covariate were included in additional
      logistic regression models predicting mortality and each of 11 postoperative
      outcomes. RESULTS: Operative mortality for the study cohort of 16,835 patients
      was 0.8% overall, 0.5% for the 10,884 patients with no transfusion, and 1.3% for
      the 5,951 patients who received transfusion of 1 or 2 units (odds ratio 2.44;
      confidence interval 1.74 to 3.42; p < 0.0001). The association between
      transfusion and mortality lessened after propensity adjustment but remained
      highly significant (odds ratio 1.86; confidence interval 1.21 to 2.87; p =
      0.005). Of the 11 postoperative outcomes studied, all but sternal wound infection
      and need for dialysis were also significantly associated with transfusion.
      CONCLUSIONS: Transfusion of as little as 1 or 2 units of RBCs is common and is
      significantly associated with increased morbidity and mortality after on-pump
      CABG. The relationship persists after adjustment for preoperative risk factors.
      These results suggest that aggressive attempts at blood conservation and
      avoidance of even small amounts of RBC transfusion may improve outcomes after
      CABG.

PMID- 24094522
TI  - Adenoid cystic carcinoma in the bronchus behaves more aggressively than its
      tracheal counterpart.
AB  - BACKGROUND: Primary airway adenoid cystic carcinomas (ACCs) are rare neoplasms
      and challenging to resect completely. The objective of the current study was to
      evaluate clinical and pathologic features and indicate prognostic factors based
      on different tumor locations in the airway. METHODS: From March 2001 to April
      2012, 82 consecutively operated patients were enrolled in this study with
      pathologically confirmed airway adenoid cystic carcinomas in the Shanghai Chest
      Hospital. Clinical and pathologic data were retrospectively reviewed. Survival
      analysis was performed using the Kaplan-Meier and log-rank tests. Multivariate
      analysis was performed using the Cox regression model. RESULTS: The ACCs
      originating from the bronchus were associated with older age (p = 0.021), had
      fewer positive margins (44.8% vs 84.9%, p < 0.001), and more involved lymph nodes
      (55.2% vs 14.3%, p = 0.002) than their tracheal counterparts. The overall
      survival after resection of all ACCs was 90.6% at 5 years and 56.4% at 10 years.
      Five and 10-year disease-free survival was 66.9% and 11.2%, respectively.
      Multivariate analysis indentified only dyspnea as a presenting symptom to predict
      tracheal disease-free survival (hazard ratio = 0.062, 95% confidence interval =
      0.005 to 0.785, p = 0.032). Bronchial ACCs had worse disease-free survival than
      tumors of tracheal origin (p = 0.001). CONCLUSIONS: Adenoid cystic carcinoma in
      the bronchus behaves more aggressively than its tracheal counterpart. Only
      dyspnea as a presenting symptom predicts better disease-free survival after
      resection of tracheal ACCs.

PMID- 24094523
TI  - Magnetoresistive sensor for real-time single nucleotide polymorphism genotyping.
AB  - We demonstrate a magnetoresistive sensor platform that allows for the real-time
      detection of point mutations in DNA targets. Specifically, we detect point
      mutations at two sites in the human beta globin gene. For DNA detection, the
      present sensor technology has a detection limit of about 160 pM and a dynamic
      range of about two orders of magnitude. The sensors are based on a new geometry
      for biological sensing that detects the difference between the amount of beads
      bound to a sensing pad and a local integrated negative reference pad. The
      magnetic beads are magnetised by the magnetic field arising from the sensor bias
      current such that no external magnetic fields are needed. The sensors are
      integrated in a microfluidic system with temperature control. The local negative
      reference integrated in the sensor geometry efficiently compensates for sensor
      offsets, external magnetic fields and a uniform background of magnetic beads,
      which enables real-time quantification of the specific binding of magnetic beads
      to the sensor surface under varying experimental conditions.

PMID- 24094524
TI  - Two-dimensional hybrid mesoporous Fe2O3-graphene nanostructures: a highly active
      and reusable peroxidase mimetic toward rapid, highly sensitive optical detection
      of glucose.
AB  - In this article, for the first time, two-dimensional hybrid mesoporous Fe2O3
      graphene (mFe2O3-G) nanostructures were developed as a peroxidase mimetic with
      catalytic activities superior to those of mFe2O3, G, and previously reported Fe
      based peroxidase mimetics. The high-surface-area mFe2O3 not only offers a large
      number of catalytically active sites, but also facilitates the diffusion of
      3,3,5,5-tetramethylbenzidine (TMB) and H2O2 toward G surface. On the other hand,
      G is pi-rich and thus favors the adsorption and enrichment of TMB within these
      pores. These synergistic effects lead to highly improved catalytic performances.
      Based on these findings, a simple, rapid, and highly sensitive and selective
      optical detector of glucose has been developed and demonstrated in buffer
      solution with a pretty low detection limit of 0.5 MUM. In addition, this
      nanosensor is reusable and can also be used for glucose detection in diluted
      serum.

PMID- 24094525
TI  - Acinetobacter baumannii ventilator-associated pneumonia: epidemiology, clinical
      characteristics, and prognosis factors.
AB  - OBJECTIVE: The aim of this study was to describe the epidemiological
      characteristics of Acinetobacter baumannii ventilator-associated pneumonia (VAP)
      and to identify factors predictive of a poor outcome. METHODS: A retrospective
      study was conducted over 16 months in a Tunisian intensive care unit (ICU). All
      adult patients with A. baumannii VAP were included. RESULTS: Ninety-two patients
      were included in they study; 41 (44.6%) were admitted because of multiple trauma.
      The mean age of the patients was 44.5+/-19.5 years. All patients needed
      mechanical ventilation on admission. The mean SAPS II score was 39+/-15. The mean
      delay before VAP onset was 8.1+/-4.7 days. On VAP onset, 57 patients (62%)
      developed septic shock. Only 14.2% of isolated strains were susceptible to
      imipenem; none were resistant to colistin. The mean duration of mechanical
      ventilation was 20+/-11 days. The mean duration of ICU stay was 24.3+/-18.7 days.
      ICU mortality was 60.9%. In the multivariate analysis, factors predictive of a
      poor outcome were previously known hypertension (odds ratio 5.8, 95% confidence
      interval 1.4-24.9; p=0.018) and VAP-related septic shock (odds ratio 8.5, 95%
      confidence interval 3-23.7; p<0.001). CONCLUSION: A. baumannii VAP is associated
      with a high mortality. Hemodynamic impairment is predictive of a poor outcome.

PMID- 24094526
TI  - Interleukin and neurotrophin up-regulation correlates with severity of H1N1
      infection in children: a case-control study.
AB  - OBJECTIVE: To evaluate the correlation between cytokine and neurotrophin
      expression and clinical findings, disease severity, and outcome of children with
      H1N1 influenza infection. METHODS: A prospective observational clinical study was
      performed on 15 children with H1N1 infection, 15 controls with lower respiratory
      tract infections (LRTI), and 15 non-infected children. Plasma levels of
      interleukin (IL)-1beta, IL-6, and neurotrophic factor (nerve growth factor (NGF),
      brain derived neurotrophic factor (BDNF), and glial derived neurotrophic factor
      (GDNF)) were measured using immunoenzymatic assays. RESULTS: Significantly higher
      levels of IL-1beta, IL-6, BDNF, and NGF were detected in patients with H1N1
      infection compared to LRTI controls, while there was no significant variation in
      GDNF in the two groups. IL-1beta, IL-6, BDNF, and NGF levels were significantly
      higher in H1N1 patients with more severe clinical manifestations compared to H1N1
      patients with mild clinical manifestations. Of note, IL-6 was significantly
      correlated with the severity of respiratory compromise and fever, while NGF up
      regulation was associated with the duration of cough. No correlation was found
      between interleukin and neurotrophic factor expression and outcome. CONCLUSIONS:
      H1N1 infection induces an early and significant IL-1beta, IL-6, BDNF, and NGF up
      regulation. The over-expression of these molecular markers is likely to play a
      neuroimmunomodulatory role in H1N1 infection and may contribute to airway
      inflammation and bronchial hyper-reactivity in infected children.

PMID- 24094527
TI  - Multifocal tuberculosis verrucosa cutis of 60 years duration.

PMID- 24094528
TI  - Accidental Nd:YAG laser-induced macular hole in a pediatric patient.
AB  - After being exposed to an industrial Nd:YAG laser, an 11-year-old boy developed a
      full-thickness macular hole in the right eye with resultant visual acuity of
      20/100. Five months after the initial injury, the vision was stable and the hole
      was still present. The patient underwent pars plana vitrectomy, internal limiting
      membrane peeling, and gas tamponade with prone positioning. Three months
      postoperatively, visual acuity improved to 20/25 with closure of the macular
      hole; however, there was a focal photoreceptor deficit. A review of the English
      language literature identified 15 eyes with similar macular hole injuries after
      Nd:YAG exposure. Three eyes were surgically managed. While all holes were
      successfully closed, only two experienced visual improvement.

PMID- 24094529
TI  - Adult out-of-hospital cardiac arrest based on chain of survival in Taoyuan
      County, northern Taiwan.
AB  - BACKGROUND: Most out-of-hospital cardiac arrest (OHCA) studies have been
      conducted in developed countries or metropolitan areas, and few in developing
      countries or rural areas. OBJECTIVES: The aims of this study were to determine
      the weak links in the chain of survival and to estimate the outcomes of OHCA
      patients in Taoyuan, a nonmetropolitan area in Taiwan. METHODS: A retrospective
      review and analysis of OHCA data was conducted. The three outcomes were whether a
      return of spontaneous circulation (ROSC) was achieved, whether the patient
      survived to admission, or whether the patient survived to hospital discharge.
      RESULTS: From April to December 2008, 1048 OHCA patients were resuscitated, and
      712 (67.9%) adult cardiac patients were used in this study. Among these 712
      patients, 17.8% achieved ROSC (95% confidence interval [CI] 15.2-20.8%), 16.3%
      survived to admission (95% CI 13.6-19.0%), and 1.4% survived to discharge (95% CI
      0.5-2.3%). Factors significantly associated with the three outcomes were witness
      status, response time to emergency medical services, and whether the patient had
      a shockable rhythm. Bystander cardiopulmonary resuscitation (CPR) did not add a
      notable benefit to the outcomes of OHCA. CONCLUSIONS: The survival rate of OHCA
      patients in nonmetropolitan Taiwan was very low (1.4%). Lower witnessed rate,
      lower bystander CPR rate, and longer response interval in remote areas are the
      main causes of inferior survival rate.

PMID- 24094530
TI  - [Is MRI monitoring useful in clinical practice in patients with multiple
      sclerosis? Yes].
AB  - The place of magnetic resonance imaging (MRI) in the monitoring of patients with
      multiple sclerosis (MS) is not codified except during the diagnostic phase.
      Several studies in the literature have shown that lesion load measured on an MRI
      done at the beginning of the disease or its increase during the first years had a
      predictive value, although moderate, on the occurrence of long-term disability as
      measured by the EDSS. Early worsening of brain atrophy during the early stages of
      the disease is predictive of worsening cognitive impairment in the following
      years. Perform an MRI is not required when setting up a first-line disease
      modifying therapy (DMT) such as an immunomodulatory treatment but it is useful
      because it can be used as a reference scan in case of treatment failure. The
      indications of second-line DMTs, whether prescribed in naive patients with an
      active disease or after failure of a first-line DMT, are based on combined
      criteria incorporating MRI data acquired in the previous 3 months compared with a
      recent MRI. Thus the practical criteria for failure of first-line DMTs are partly
      based on MRI. During interferon therapy, identification of disease activity on an
      MRI conducted 1 year after the start of the treatment can predict treatment
      failure in combination with clinical criteria, such as relapses occurring during
      the first year. Finally, MRI is essential to the safety monitoring of patients on
      natalizumab to detect progressive multifocal leukoencephalopathies (PML). In
      patients at high risk for PML, tested positive for JC virus antibodies and having
      received natalizumab for more than 2 years, it could be proposed to do a short
      MRI with FLAIR and diffusion weighted imaging sequences every 3 months to detect
      preclinical PML.

PMID- 24094531
TI  - Factors affecting variation of different measures of cheese yield and milk
      nutrient recovery from an individual model cheese-manufacturing process.
AB  - Cheese yield (CY) is the most important technological trait of milk, because
      cheese-making uses a very high proportion of the milk produced worldwide. Few
      studies have been carried out at the level of individual milk-producing animals
      due to a scarcity of appropriate procedures for model-cheese production, the
      complexity of cheese-making, and the frequent use of the fat and protein (or
      casein) contents of milk as a proxy for cheese yield. Here, we report a high
      throughput cheese manufacturing process that mimics all phases of cheese-making,
      uses 1.5-L samples of milk from individual animals, and allows the simultaneous
      processing of 15 samples per run. Milk samples were heated (35 degrees C for 40
      min), inoculated with starter culture (90 min), mixed with rennet (51.2
      international milk-clotting units/L of milk), and recorded for gelation time.
      Curds were cut twice (10 and 15 min after gelation), separated from the whey,
      drained (for 30 min), pressed (3 times, 20 min each, with the wheel turned each
      time), salted in brine (for 60 min), weighed, and sampled. Whey was collected,
      weighed, and sampled. Milk, curd, and whey samples were analyzed for pH, total
      solids, fat content, and protein content, and energy content was estimated. Three
      measures of percentage cheese yield (%CY) were calculated: %CY(CURD),
      %CY(SOLIDS), and %CY(WATER), representing the ratios between the weight of fresh
      curd, the total solids of the curd, and the water content of the curd,
      respectively, and the weight of the milk processed. In addition, 3 measures of
      daily cheese yield (dCY, kg/d) were defined, considering the daily milk yield.
      Three measures of nutrient recovery (REC) were computed: REC(FAT), REC(PROTEIN),
      and REC(SOLIDS), which represented the ratio between the weights of the fat,
      protein, and total solids in the curd, respectively, and the corresponding
      components in the milk. Energy recovery, REC(ENERGY), represented the energy
      content of the cheese compared with that in the milk. This procedure was used to
      process individual milk samples obtained from 1,167 Brown Swiss cows reared in 85
      herds of the province of Trento (Italy). The assessed traits exhibited almost
      normal distributions, with the exception of REC(FAT). The average values (+/- SD)
      were as follows: %CY(CURD)=14.97+/-1.86, %CY(SOLIDS)=7.18+/-0.92,
      %CY(WATER)=7.77+/-1.27, dCY(CURD)=3.63+/-1.17, dCY(SOLIDS)=1.74+/-0.57,
      dCY(WATER)=1.88+/-0.63, REC(FAT)=89.79+/-3.55, REC(PROTEIN)=78.08+/-2.43,
      REC(SOLIDS)=51.88+/-3.52, and REC(ENERGY)=67.19+/-3.29. All traits were highly
      influenced by herd-test-date and days in milk of the cow, moderately influenced
      by parity, and weakly influenced by the utilized vat. Both %CY(CURD) and
      dCY(CURD) depended not only on the fat and protein (casein) contents of the milk,
      but also on their proportions retained in the curd; the water trapped in curd
      presented an higher variability than that of %CY(SOLIDS). All REC traits were
      variable and affected by days in milk and parity of the cows. The described model
      cheese-making procedure and the results obtained provided new insight into the
      phenotypic variation of cheese yield and recovery traits at the individual level.

PMID- 24094532
TI  - Reproductive performance of dairy cows resynchronized after pregnancy diagnosis
      at 31 (+/-3 days) after artificial insemination (AI) compared with
      resynchronization at 31 (+/-3 days) after AI with pregnancy diagnosis at 38 (+/-3
      days) after AI.
AB  - An important part of reproductive management programs on dairy farms is
      identification of nonpregnant cows and early re-insemination to achieve higher
      pregnancy rates. The objective of this study was to compare the effect on
      reproductive performance and pregnancy loss of 2 pregnancy diagnosis protocols:
      (1) pregnancy diagnosis performed 31+/-3 d after artificial insemination (AI) by
      ultrasonography (ULTRA), and (2) resynchronization started 31+/-3 d after AI but
      with pregnancy diagnosis performed 38+/-3 d after AI by palpation per rectum
      (PALP). Cows were randomly allocated into 1 of the 2 management programs. For
      cows enrolled in ULTRA, the initial pregnancy diagnosis (P1) was performed by
      transrectal ultrasonography at 31+/-3 d after AI, and nonpregnant cows were
      enrolled in the Ovsynch protocol for resynchronization of ovulation to receive
      timed AI (TAI). For cows enrolled in PALP, the Ovsynch protocol for
      resynchronization of ovulation to receive TAI was initiated at 31+/-3 d after AI
      regardless of pregnancy status, with the initial pregnancy diagnosis (P1)
      performed by palpation per rectum at 38+/-3 d after AI. For both groups,
      reconfirmation of pregnancy was performed by palpation per rectum at 63+/-3 d
      after AI (P2). Cows were inseminated after detection of estrus by use of activity
      monitors at any time during the study. Two levels of activity were used as a
      reference for cows AI after detection of estrus based on activity: an activity
      level of >=2 when a cow was coded in DairyComp 305 (Valley Agricultural Software,
      Tulare, CA) as open (nonpregnant) and an activity level of >=3 when the pregnancy
      status of the cow was unknown. Our findings showed that the odds of pregnancy
      loss cows in ULTRA was 2 times higher between P1 and P2 compared with that of
      cows in PALP. Furthermore, pregnancy diagnosis method (ULTRA vs. PALP) did not
      have a significant effect on the Cox proportional hazard of pregnancy at P2. The
      occurrence of assisted parturition, metritis, or retained placenta was associated
      with a reduced hazard of pregnancy at P2. An economic analysis was performed by
      simulating a 1,000-cow commercial dairy herd using a decision support tool to
      estimate the net present value (NPV; $/cow per yr) from using the 2 different
      pregnancy diagnosis methods. The analysis revealed minor differences in NPV
      between the programs, depending on the cost to perform ULTRA or PALP. In summary,
      we observed no difference in the reproductive performance and only a minor and
      fluctuating economic difference when using either PALP or ULTRA for pregnancy
      diagnosis of dairy cows. 

PMID- 24094533
TI  - Carbohydrate supplements and their effects on pasture dry matter intake, feeding
      behavior, and blood factors associated with intake regulation.
AB  - Supplementary feeds are offered to grazing dairy cows to increase dry matter (DM)
      and metabolizable energy (ME) intakes; however, offering feed supplements reduces
      pasture DM intake, a phenomenon known as substitution. The objective of the study
      was to investigate changes in blood factors associated with intake regulation in
      monogastric species in pasture-fed dairy cows supplemented with either a starch-
      or nonforage fiber-based concentrate. Fifteen multiparous Friesian * Jersey cross
      cows were assigned to 1 of 3 treatments at calving. Measurements were undertaken
      in wk 8 of lactation. Treatments were pasture only, pasture plus a starch-based
      concentrate (3.5 kg of DM/cow per day; STA), and pasture plus a nonforage fiber
      based concentrate (4.4 kg of DM/cow per day). Pelleted concentrates were fed at
      an isoenergetic rate in 2 equal portions at a.m. and p.m. milkings. Measurements
      were undertaken to investigate differences in pasture DM intake, feeding
      behavior, and profiles of blood factors for 4h after a.m. and p.m. milkings, the
      periods of intensive feeding in grazing cows. Supplementing cows with STA
      concentrate reduced pasture DM intake to a greater extent than the fiber
      concentrate, although time spent eating did not differ between treatments. The
      blood factor response to feeding differed between the a.m. and p.m. feeding
      events. Blood factors associated with a preprandial or fasted state were elevated
      prefeeding in the a.m. and declined following feeding, whereas satiety factors
      increased. In comparison, the blood factor response to feeding in the p.m.
      differed, with responses to feeding delayed for most factors. Plasma ghrelin
      concentration increased during the p.m. feeding event, despite the consumption of
      feed and the positive energy state remaining from the previous a.m. feeding,
      indicating that environmental factors (e.g., sunset) supersede physiological cues
      in regulating feeding behavior. The greater reduction in pasture DM intake for
      the STA treatment in the p.m. may be related to the level of hunger or satiety
      before the feeding event and not solely to the consumption of supplement. Data
      indicate that neuroendocrine factors are, at least in part, responsible for the
      substitution of pasture for supplementary feeds.

PMID- 24094534
TI  - The use of Fourier-transform infrared spectroscopy to predict cheese yield and
      nutrient recovery or whey loss traits from unprocessed bovine milk samples.
AB  - Cheese yield is an important technological trait in the dairy industry in many
      countries. The aim of this study was to evaluate the effectiveness of Fourier
      transform infrared (FTIR) spectral analysis of fresh unprocessed milk samples for
      predicting cheese yield and nutrient recovery traits. A total of 1,264 model
      cheeses were obtained from 1,500-mL milk samples collected from individual Brown
      Swiss cows. Individual measurements of 7 new cheese yield-related traits were
      obtained from the laboratory cheese-making procedure, including the fresh cheese
      yield, total solid cheese yield, and the water retained in curd, all as a
      percentage of the processed milk, and nutrient recovery (fat, protein, total
      solids, and energy) in the curd as a percentage of the same nutrient contained in
      the milk. All individual milk samples were analyzed using a MilkoScan FT6000 over
      the spectral range from 5,000 to 900 wavenumber * cm(-1). Two spectral
      acquisitions were carried out for each sample and the results were averaged
      before data analysis. Different chemometric models were fitted and compared with
      the aim of improving the accuracy of the calibration equations for predicting
      these traits. The most accurate predictions were obtained for total solid cheese
      yield and fresh cheese yield, which exhibited coefficients of determination
      between the predicted and measured values in cross-validation (1-VR) of 0.95 and
      0.83, respectively. A less favorable result was obtained for water retained in
      curd (1-VR=0.65). Promising results were obtained for recovered protein (1
      VR=0.81), total solids (1-VR=0.86), and energy (1-VR=0.76), whereas recovered fat
      exhibited a low accuracy (1-VR=0.41). As FTIR spectroscopy is a rapid, cheap,
      high-throughput technique that is already used to collect standard milk recording
      data, these FTIR calibrations for cheese yield and nutrient recovery highlight
      additional potential applications of the technique in the dairy industry,
      especially for monitoring cheese-making processes and milk payment systems. In
      addition, the prediction models can be used to provide breeding organizations
      with information on new phenotypes for cheese yield and milk nutrient recovery,
      potentially allowing these traits to be enhanced through selection. 

PMID- 24094535
TI  - Pregnancy per artificial insemination in lactating dairy cows subjected to 2
      different intervals from presynchronization to initiation of Ovsynch protocol.
AB  - A protocol for presynchronization of ovarian status with 2 injections of
      PGF2alpha given 14 d apart, with the last PGF2alpha injection given 12 or 14 d
      before Ovsynch increases pregnancy per artificial insemination (P/AI) in dairy
      cows. We determined the efficacy of reducing the interval from the last PGF2alpha
      injection (500 MUg of cloprostenol) of presynchronization to initiation of
      Ovsynch on response to treatment and P/AI. Lactating dairy cows were assigned to
      an Ovsynch protocol, with the initial injection of GnRH given either 9 (PRE-9;
      n=135) or 12d (PRE-12; n=135) after the second PGF2alpha injection of
      presynchronization. The Ovsynch protocol consisted of 2 injections of 100 MUg of
      GnRH given 9 d apart and 1 injection of PGF2alpha given 7 d after the initial
      GnRH injection, and cows were subjected to timed artificial insemination (TAI;
      70+/-3.5 DIM) approximately 16 h after the second GnRH injection. Body condition
      score (1-5 scale) was recorded at TAI. Blood samples were taken for progesterone
      determination at the PGF2alpha injection of Ovsynch, at TAI, and at 11 d after
      TAI. Ultrasonographic examinations were done in all cows at the second PGF2alpha
      injection of presynchronization, initial GnRH injection, PGF2alpha injection of
      Ovsynch, at TAI, and 24 h after TAI for cyclicity status and ovarian responses to
      treatments, and at 32 and 60 d after TAI for confirmation of pregnancy. Overall,
      29 cows (10.7%) were determined acyclic or cystic and excluded from the study.
      The percentage of cows responding to initial GnRH injection (62.2 vs. 61.5%) did
      not differ between PRE-9 and PRE-12 but more cows in the PRE-9 group failed to
      respond to PGF2alpha treatment of Ovsynch compared with PRE-12 (22.7 vs. 10.7%).
      Body condition score at TAI (2.9+/-0.02) and mean ovulatory follicle diameter
      (16.4+/-0.2 mm) were not different between treatments. Overall P/AI at 32 d was
      reduced in PRE-9 (33.6%) compared with PRE-12 (44.3%) but pregnancy losses (5.0
      vs. 3.7%) did not differ between treatments. Primiparous cows in the PRE-12 group
      had higher mean progesterone concentration 11 d after TAI and greater P/AI 32
      after TAI than primiparous cows in the PRE-9 group (6.4+/-0.5 vs. 4.6+/-0.5 ng/mL
      and 55.8 vs. 30.0%, respectively). In conclusion, reducing the interval from the
      last PGF2alpha injection of the presynchronization treatment to initiation of
      Ovsynch (from 12 to 9 d) did not affect ovulatory response to initial GnRH
      injection but reduced response to PGF2alpha injection of Ovsynch and P/AI at 32
      and 60 d after TAI. The reduction in P/AI was particularly evident in primiparous
      cows of the PRE-9 group.

PMID- 24094536
TI  - Development of an automatic cow body condition scoring using body shape signature
      and Fourier descriptors.
AB  - Body condition evaluation is a common tool to assess energy reserves of dairy
      cows and to estimate their fatness or thinness. This study presents a computer
      vision tool that automatically estimates cow's body condition score. Top-view
      images of 151 cows were collected on an Israeli research dairy farm using a
      digital still camera located at the entrance to the milking parlor. The cow's
      tailhead area and its contour were segmented and extracted automatically. Two
      types of features of the tailhead contour were extracted: (1) the angles and
      distances between 5 anatomical points; and (2) the cow signature, which is a 1
      dimensional vector of the Euclidean distances from each point in the normalized
      tailhead contour to the shape center. Two methods were applied to describe the
      cow's signature and to reduce its dimension: (1) partial least squares
      regression, and (2) Fourier descriptors of the cow signature. Three prediction
      models were compared with manual scores of an expert. Results indicate that (1)
      it is possible to automatically extract and predict body condition from color
      images without any manual interference; and (2) Fourier descriptors of the cow's
      signature result in improved performance (R(2)=0.77). 

PMID- 24094537
TI  - Effects of roughage source, amount, and particle size on behavior and
      gastrointestinal health of veal calves.
AB  - The European Union 1997 Directive, stipulating that veal calves should be fed a
      minimum of 50 to 250 g of fibrous feed from 8 to 20 wk of age, is vague. A
      fibrous feed ration maximum of 250 g has been implicated in welfare issues,
      namely the occurrence of abnormal oral behaviors and poor gastrointestinal
      health. Past research suggests that this amount is insufficient to prevent the
      development of abnormal oral behaviors and enabling good rumen development.
      Different sources and particle sizes of roughage could lead to very different
      welfare outcomes. In a 3*2 * 2 factorial design, 240 group-housed calves (10+/-1
      d; 46.1+/-0.1 kg) were fed different roughage sources (straw, maize silage, or
      maize cob silage; the latter 2 were dried and provided no extra moisture compared
      with straw) in 2 amounts (250 or 500 g of dry matter per day), and 2 particle
      sizes (chopped or ground). Roughage was supplemented to milk replacer (MR) from 2
      wk after arrival. In addition, 60 calves were fed 1 of 3 additional control
      treatments: MR only (n=20), MR plus an iron supplement (n=20), or MR plus ad
      libitum hay (n=20). Oral behaviors were recorded using instantaneous scan
      sampling at 2-min intervals for 2 h in 3 periods per day, at 12 and 22 wk of age.
      Calves were slaughtered at 24 wk of age and rumen and abomasal health parameters
      were recorded. Limited provision of straw resulted in behavior comparable with
      that from unlimited provision of hay, with reduced tongue playing and oral
      manipulation of the environment, as well as increased chewing compared with diets
      with no roughage supplement. Straw prevented ruminal hairballs, but impaired
      rumen development and increased abomasal damage. A higher ration of roughage
      increased chewing (12 wk), decreased oral manipulation of the trough (12 and 22
      wk) and the pen (22 wk), and increased rumen weight. However, more roughage led
      to increased abomasal damage for certain parameters. Longer feed particles had no
      obvious benefits for behavior, but decreased hairball prevalence. Overall,
      unlimited hay had the highest benefit for both behavior and gastrointestinal
      health. Adding iron to the MR did not alter behavior or gastrointestinal health
      compared with MR without iron supplement. This study demonstrated that different
      roughage sources, amounts, and particle sizes have different effects on veal calf
      behavior and gastrointestinal health, and hence on veal calf welfare.

PMID- 24094538
TI  - Estimation of feed crude protein concentration and rumen degradability by Fourier
      transform infrared spectroscopy.
AB  - Currently, rapid methods are needed for feed analysis. This study examined the
      potential of Fourier-transform infrared (FTIR) spectroscopy to predict the
      nutritional value of a wide range of feeds for ruminants, as an alternative to
      the in situ technique. Moreover, we investigated whether universal equations
      could be developed that would allow the low-cost determination of crude protein
      (CP) concentrations and their kinetics of degradation into the rumen. Protein
      nutritional values of 663 samples comprising 80 different feed types were
      determined in terms of concentrations of CP, water-soluble CP (CP(WS)), total
      tract mobile bag CP digestibility (CP(TTD)), and in situ CP degradability,
      including the rumen soluble fraction (CP(A)), the degradable but not soluble
      fraction (CP(B)), rate of CP(B) degradation (CP(C)), effective degradability
      (CP(ED)), and potential degradability (CPPD). Infrared spectra of dry samples
      were collected by attenuated total reflectance from 4000 to 600 cm(-1). Models
      were developed by partial least squares (PLS) regression in a randomly selected
      subset of samples, and the precision of the equations was confirmed by using an
      external validation set. Analysis by FTIR spectroscopy was sufficiently sensitive
      to allow the accurate prediction of sample CP concentration (R(2)=0.92) and to
      classify feeds according to their CPWS concentrations using universal models
      (R(2)=0.78) that included all sample types. Moreover, substantial improvements in
      predictions were observed when samples were subdivided in groups. Models for
      forages led to accurate predictions of CP(WS) and fractions CP(A) and CP(B)
      (R(2)>0.83), whereas models for CP(TTD) and CP(ED) could be used for screening
      purposes (R(2)>0.67). This study showed that models for protein-rich concentrates
      alone could also be used for screening according to the feed concentrations of
      CP(WS), CP(TTD), CP(ED), CP(A), and CP(B), but models for energy-rich
      concentrates gave relatively poor predictions. The general difficulty observed in
      predicting CP(C) is because of a low correlation between FTIR spectra and the
      kinetics of CP degradation, which may be the result of large variation in the
      reference method (i.e., in situ degradation studies) and perhaps also because of
      the presence of compounds that can modify the CP degradation pattern in the
      rumen. In conclusion, FTIR spectroscopy should be considered as a low-cost
      alternative in the feed evaluation industry.

PMID- 24094539
TI  - Genetic parameters of different measures of cheese yield and milk nutrient
      recovery from an individual model cheese-manufacturing process.
AB  - Cheese yield (CY) is an important technological trait in the dairy industry, and
      the objective of this study was to estimate the genetic parameters of cheese
      yield in a dairy cattle population using an individual model-cheese production
      procedure. A total of 1,167 Brown Swiss cows belonging to 85 herds were sampled
      once (a maximum of 15 cows were sampled per herd on a single test day, 1 or 2
      herds per week). From each cow, 1,500 mL of milk was processed according to the
      following steps: milk sampling and heating, culture addition, rennet addition,
      gelation-time recording, curd cutting, whey draining and sampling, wheel
      formation, pressing, salting in brine, weighing, and cheese sampling. The
      compositions of individual milk, whey, and curd samples were determined. Three
      measures of percentage cheese yield (%CY) were calculated: %CY(CURD),
      %CY(SOLIDS), and %CY(WATER), which represented the ratios between the weight of
      fresh curd, the total solids of the curd, and the water content of the curd,
      respectively, and the weight of the milk processed. In addition, 3 measures of
      daily cheese yield (dCY, kg/d) were defined, considering the daily milk yield.
      Three measures of nutrient recovery (REC) were computed: REC(FAT), REC(PROTEIN),
      and REC(SOLIDS), which represented the ratio between the weights of the fat,
      protein, and total solids in the curd, respectively, and the corresponding
      nutrient in the milk. Energy recovery, REC(ENERGY), represented the energy
      content of the cheese versus that in the milk. For statistical analysis, a
      Bayesian animal model was implemented via Gibbs sampling. The effects of parity
      (1 to >=4), days in milk (6 classes), and laboratory vat (15 vats) were assigned
      flat priors; those of herd-test-date, animal, and residual were given Gaussian
      prior distributions. Intra-herd heritability estimates of %CY(CURD), %CY(SOLIDS),
      and %CY(WATER) ranged from 0.224 to 0.267; these were larger than the estimates
      obtained for milk yield (0.182) and milk fat content (0.122), and similar to that
      for protein content (0.275). Daily cheese yields showed heritability estimates
      similar to those of daily milk yield. The trait %CY(WATER) showed a highly
      positive genetic correlation with %CY(SOLIDS) (0.87), whereas their phenotypic
      correlation was moderate (0.37), and the fat and protein contents of milk showed
      high genetic correlations with %CY traits. The heritability estimates of
      REC(PROTEIN) and REC(FAT) were larger (0.490 and 0.208, respectively) than those
      obtained for the protein and fat contents of milk, and the genetic relationships
      between REC(PROTEIN) and REC(FAT) with milk protein and fat content were low or
      moderate; REC(PROTEIN) and REC(FAT) were moderately correlated with the %CY
      traits and highly correlated with REC(SOLIDS) and REC(ENERGY). Both REC(SOLIDS)
      and REC(ENERGY) were heritable (0.274 and 0.232), and showed high correlations
      with each other (0.96) and with the %CY traits (0.83 to 0.97). Together, these
      findings demonstrate the existence of economically important, genetically
      determined variability in cheese yield that does not depend solely upon the fat
      and protein contents of milk, but also relies on the ability of the coagulum to
      retain the highest possible proportions of the available protein, fat, and water.
      Exploitation of this interesting genetic variation does not seem to be feasible
      through direct measurement of the phenotype in cows at the population level.
      Instead, further research is warranted to examine possible means for indirect
      prediction, such as through assessing the mid-infrared spectra of milk samples.

PMID- 24094540
TI  - Frequency of melanocytic nevi in psoriatic patients is related to treatment and
      not to disease severity.
AB  - BACKGROUND: Few data exist on the relationship between psoriasis and melanocytic
      lesions. OBJECTIVES: We sought to investigate number of melanocytic nevi in
      psoriatic patients compared with control subjects and its relationship with
      disease severity and treatment. METHODS: We performed a prospective study in 189
      psoriatic patients and 189 control subjects. Sociodemographic and clinical data
      were recorded for all participants. RESULTS: As compared with control subjects,
      patients had fewer nevi overall [chi(2)(5) = 52.24, P < .001], fewer nevi less
      than 5 mm [chi(2)(4) = 60.28, P < .001], and fewer congenital nevi [chi(2)(1) =
      10.41, P = .002]; no differences in atypical nevi and family history of cancer,
      including melanoma, were observed. Among psoriatic patients, number of biologics
      used was a risk factor for a higher nevus count [odds ratio 1.35 (95% CI 1.04
      1.76), P = .02] whereas disease severity did not correlate with number of nevi.
      LIMITATIONS: Low number of psoriatic patients naive to systemic therapies was a
      limitation. CONCLUSIONS: Psoriatic patients have fewer nevi than control
      subjects. Frequency of nevi in psoriatic patients is related to treatment, not to
      disease severity.

PMID- 24094541
TI  - Simulation of plastic surgery and microvascular procedures using perfused fresh
      human cadavers.
AB  - INTRODUCTION: Surgical simulation models are often limited by their lack of
      fidelity, which hinders their essential purpose, making a better surgeon. Fresh
      cadaveric tissue is a superior model of simulation owing to its approximation of
      live tissue. One major unresolved difference between dead and live tissue is
      perfusion. Here, we propose a means of enhancing the fidelity of cadaveric
      simulation through the development of a perfused cadaveric model whereby
      simulation is further able to approach life-like surgery and teach one of the
      more technically demanding skills of plastic surgery: microsurgery. METHOD: Fresh
      tissue human cadavers were procured according to university protocol. Perfusion
      was performed via cannulation of large vessels, and arterial and venous pressure
      was maintained by centrifugal circulation. Skin perfusion was evaluated with
      incisions in the perfused regions and was evaluated using indocyanine green
      angiography. Surgical simulations were selected to broadly evaluate applicability
      to plastic surgical education. RESULT: Surgical simulation of 38 procedures
      ranging in complexity from skin excisions to microsurgical cases was performed
      with high priority given to the accurate simulation of clinical procedures. Flap
      dissections included perforator flaps, muscle flaps, and fasciocutaneous flaps.
      Effective perfusion was noted with ICG angiography and notable bleeding vessels.
      Microsurgical flap transfer was successfully performed. CONCLUSION: We report the
      establishment of a high fidelity surgical simulation using a perfused fresh
      tissue model in a realistic environment akin to the operating room. We anticipate
      utilization of this model prior to entering the operating room will enhance
      surgical ability and offer a valuable resource in plastic surgical education.

PMID- 24094542
TI  - Childhood atopic dermatitis and warts are associated with increased risk of
      infection: a US population-based study.
AB  - BACKGROUND: Previous studies suggested that atopic dermatitis (AD) is associated
      with aberrant immune responses, which might predispose toward both cutaneous and
      extracutaneous infections. The goal of this study was to determine whether
      childhood AD is associated with increased risk of warts, extracutaneous
      infections, and other atopic diseases and how these disorders cosegregate.
      METHODS: The 2007 National Health Interview Survey from a nationally
      representative sample of 9417 children age 0 to 17 years was used. RESULTS:
      Children with AD and other atopic disease had higher odds of warts. In contrast,
      children with AD with or without other atopic disease had higher odds of
      extracutaneous infections, including strep throat, other sore throat, head or
      chest cold, influenza/pneumonia, sinus infections, recurrent ear infections,
      chickenpox, and urinary tract infections (P < .0001). Children with AD and other
      atopic disease had a higher number of infections than those with either disorder
      by itself (P < .0001). Warts were also associated with increased odds of all
      extracutaneous infections (P < .0001), except recurrent ear infections. Children
      with warts and AD had a higher number of infections than those with either
      disorder alone (P < .0001). Finally, children with AD and warts had higher odds
      of ever receiving a diagnosis of asthma, current asthma, asthma exacerbation in
      the past year, hay fever, and food allergy. Children with AD with warts had even
      higher odds of asthma, hay fever, and food allergies than those with AD and no
      warts. CONCLUSIONS: The associations between childhood AD, atopic disease, warts,
      and extracutaneous infections suggest that barrier disruption, immune disruption,
      or both contribute to susceptibility to warts and extracutaneous infections in
      children.

PMID- 24094543
TI  - Eosinophilic asthma: insights into the effects of reducing IL-5 receptor-positive
      cell levels.

PMID- 24094544
TI  - Adult eczema prevalence and associations with asthma and other health and
      demographic factors: a US population-based study.
AB  - BACKGROUND: Little is known about the epidemiology of eczema in adults. The goal
      of this study was to determine the prevalence of and associations with adult
      eczema in the United States. METHODS: We used the 2010 National Health Interview
      Survey from a nationally representative sample of 27,157 adults age 18 to 85
      years. RESULTS: Overall, the 1-year prevalence of eczema was 10.2% (95% CI, 9.7%
      to 10.6%). The 1-year prevalence of eczema with asthma and/or hay fever was 3.2%
      (95% CI, 2.8% to 3.3%). Adult eczema was associated with higher prevalence of
      asthma (P < .001, Rao-Scott chi(2) test), more asthma attacks in the past year (P
      < .001), and more persistent asthma (P = .02). In multivariate models eczema
      prevalence was significantly higher in older participants; female subjects; those
      with Hispanic ethnicity, US birthplace, and higher level of household education;
      and those currently working (all P <= .02, logistic regression). CONCLUSIONS:
      This study provides US population-based estimates of eczema prevalence and asthma
      associations in adults. The results suggest multiple demographic and
      socioeconomic influences on the US prevalence of adult eczema.

PMID- 24094545
TI  - Do children really outgrow their eczema, or is there more than one eczema?

PMID- 24094546
TI  - The long road to optimal management for chronic granulomatous disease.

PMID- 24094547
TI  - Meta-analysis of air pollution exposure association with allergic sensitization
      in European birth cohorts.
AB  - BACKGROUND: Evidence on the long-term effects of air pollution exposure on
      childhood allergy is limited. OBJECTIVE: We investigated the association between
      air pollution exposure and allergic sensitization to common allergens in children
      followed prospectively during the first 10 years of life. METHODS: Five European
      birth cohorts participating in the European Study of Cohorts for Air Pollution
      Effects project were included: BAMSE (Sweden), LISAplus and GINIplus (Germany),
      MAAS (Great Britain), and PIAMA (The Netherlands). Land-use regression models
      were applied to assess the individual residential outdoor levels of particulate
      matter with an aerodynamic diameter of less than 2.5 MUm (PM2.5), the mass
      concentration of particles between 2.5 and 10 MUm in size, and levels of
      particulate matter with an aerodynamic diameter of less than 10 MUm (PM10), as
      well as measurement of the blackness of PM2.5 filters and nitrogen dioxide and
      nitrogen oxide levels. Blood samples drawn at 4 to 6 years of age, 8 to 10 years
      of age, or both from more than 6500 children were analyzed for allergen-specific
      serum IgE against common allergens. Associations were assessed by using multiple
      logistic regression and subsequent meta-analysis. RESULTS: The prevalence of
      sensitization to any common allergen within the 5 cohorts ranged between 24.1%
      and 40.4% at the age of 4 to 6 years and between 34.8% and 47.9% at the age of 8
      to 10 years. Overall, air pollution exposure was not associated with
      sensitization to any common allergen, with odds ratios ranging from 0.94 (95% CI,
      0.63-1.40) for a 1 * 10(-5) ? m(-1) increase in measurement of the blackness of
      PM2.5 filters to 1.26 (95% CI, 0.90-1.77) for a 5 MUg/m(3) increase in PM2.5
      exposure at birth address. Further analyses did not provide consistent evidence
      for a modification of the air pollution effects by sex, family history of atopy,
      or moving status. CONCLUSION: No clear associations between air pollution
      exposure and development of allergic sensitization in children up to 10 years of
      age were revealed.

PMID- 24094548
TI  - Red meat allergy in Sweden: association with tick sensitization and B-negative
      blood groups.

PMID- 24094549
TI  - A 3D anthropometric analysis of the orolabial region in Chinese young adults.
AB  - The orolabial region undergoes considerable changes after orthognathic surgery or
      orthodontic treatment. Ethnicity, age, and sex-specific norms are needed during
      the planning of interventions in this region. In 2008 the Br J Oral Maxillofac
      Surg published anthropometric measurements of the lips of Chinese children, but
      to our knowledge such reference data for young Chinese adults are not currently
      available. We therefore used digital anthropometry on 3-dimensional craniofacial
      images acquired from 103 healthy young Chinese adults with Class I skeletal
      pattern. Anthropometric landmarks were identified, which provided linear and
      angular measurements. All orolabial measurements were significantly larger in men
      than women, with the exception of the labiomental angle. In contrast, there were
      no sex differences in the anthropometric proportions. We therefore provide what
      we think are the first cross-sectional norms available for young Chinese adults.
      These norms can be used to evaluate the morphology of the lips objectively for
      preoperative diagnosis, planning of treatment, and assessment of postoperative
      outcomes. 

PMID- 24094550
TI  - Regulation of ROS-independent ERK signaling rescues replicative cellular
      senescence in ex vivo expanded human c-kit-positive cardiac progenitor cells.
AB  - BACKGROUNDS: Although the rescue of cellular senescence during ex vivo expansion
      of human-derived cardiac progenitor cells (hCPC) is critical for the application
      of autologous stem cell therapy in cardiovascular disease, the underlying
      molecular pathways during replicative senescence in hCPC have not been fully
      defined. Thus, we examined whether the regulation of mitogen-activated protein
      kinases activation could facilitate the recovery of human c-kit-positive hCPCs
      (hCPC(c-kit+)) and whether senescence is reactive oxygen species (ROS)-dependent
      or -independent. METHODS AND RESULTS: To investigate the molecular pathways of
      replicative cellular senescence, we first evaluated cellular senescence in ex
      vivo-expanded hCPC(c-kit+) by using senescence-associated beta-galactosidase (SA
      beta-gal) activity with enlarged cytoplasm and observed increased expression of
      cell senescence-related pivotal molecules, including TP53, cleavage Mdm2 (cMdm2),
      and Mdm2. Unexpectedly, we found that the extracellular signal-regulated kinase
      (ERK) was markedly activated in aged hCPC(c-kit+), with reduced proliferative
      activity. SA-beta-gal activity and cytoplasm size in senescent hCPC(c-kit+) were
      significantly reduced, with reduced TP53 and cMdm2 expression after treatment
      with a specific ERK inhibitor (U0126). We examined whether the signaling in ERK
      inhibitory rescue of hCPC(c-kit+) senescence is ROS-dependent. Interestingly, the
      increased ROS level was not changed after treatment with a specific ERK
      inhibitor. Similarly, the increased expression levels of endogenous antioxidant
      enzymes, e.g., peroxiredoxin (Prdx)-1 and 2, in senescent hCPC(c-kit+) were not
      changed after treatment with a specific ERK inhibitor. CONCLUSIONS: From the
      above results, we conclude that the specific inhibition of ERK during cellular
      senescence might rescue bioactivities of senescent hCPC(c-kit+) in a ROS
      independent manner.

PMID- 24094552
TI  - Optimal serum phenylalanine for adult patients with phenylketonuria.
AB  - High serum phenylalanine in adult patients with phenylketonuria (PKU) causes
      neuropsychological and psychosocial problems that can be resolved by
      phenylalanine-restricted diet. Therefore, PKU patients must continue to adhere to
      phenylalanine-restricted diet for life, although the optimal serum phenylalanine
      level in later life has yet to be established. The purpose of this review was to
      establish the optimal serum phenylalanine level in later life of PKU patients. We
      evaluated oxidative stress status, nitric oxide metabolism, cholesterol-derived
      oxysterols, vitamin D and bone status, and magnetic resonance imaging (MRI) in
      adult PKU patients according to serum phenylalanine level. Oxidative stress
      increased markedly at serum phenylalanine of 700-800 MUmol/L. Serum phenylalanine
      higher than 700-850 MUmol/L correlated with the disturbance of nitric oxide
      regulatory system. Adult PKU patients had poor vitamin D status and exhibited
      predominance of bone resorption over bone formation. In the brain, the levels of
      24S-hydroxycholesterol, a marker of brain cholesterol elimination, were low at
      serum phenylalanine levels exceeding 650 MUmol/L. MRI studies showed high signal
      intensity in deep white matter on T2-weighted and FLAIR images of PKU patients
      with serum phenylalanine greater than 500 MUmol/L, with decreased apparent
      diffusion coefficients. Changes in most parameters covering the entire body
      organs in adult PKU were almost acceptable below 700-800 MUmol/L of phenylalanine
      level. However, the optimal serum phenylalanine level should be 500 MUmol/L or
      less in later life for the brain to be safe.

PMID- 24094553
TI  - A new definition for an old entity: improved definition of mitral valve prolapse
      using three-dimensional echocardiography and color-coded parametric models.
AB  - BACKGROUND: Differentiating between mitral valve (MV) prolapse (MVP) and MV
      billowing (MVB) on two-dimensional echocardiography is challenging. The aim of
      this study was to test the hypothesis that color-coded models of maximal leaflet
      displacement from the annular plane into the atrium derived from three
      dimensional transesophageal echocardiography would allow discrimination between
      these lesions. METHODS: Three-dimensional transesophageal echocardiographic
      imaging of the MV was performed in 50 patients with (n = 38) and without (n = 12)
      degenerative MV disease. Definitive diagnosis of MVP versus MVB was made using
      inspection of dynamic three-dimensional renderings and multiple two-dimensional
      cut planes extracted from three-dimensional data sets. This was used as a
      reference standard to test an alternative approach, wherein the color-coded
      parametric models were inspected for integrity of the coaptation line and
      location of the maximally displaced portion of the leaflet. Diagnostic
      interpretations of these models by two independent readers were compared with the
      reference standard. RESULTS: In all cases of MVP, the color-coded models depicted
      loss of integrity of the coaptation line and maximal leaflet displacement
      extending to the coaptation line. MVB was depicted by preserved leaflet
      apposition with maximal displacement away from the coaptation line.
      Interpretation of the 50 color-coded models by novice readers took 5 to 10 min
      and resulted in good agreement with the reference technique (kappa = 0.81 and
      kappa = 0.73 for the two readers). CONCLUSIONS: Three-dimensional color-coded
      models provide a static display of MV leaflet displacement, allowing
      differentiation between MVP and MVB, without the need to inspect multiple planes
      and while taking into account the saddle shape of the mitral annulus.

PMID- 24094551
TI  - Characterization and application of a disease-cell model for a neurodegenerative
      lysosomal disease.
AB  - Disease-cell models that recapitulate specific molecular phenotypes are essential
      for the investigation of molecular pathogenesis of neurodegenerative diseases
      including lysosomal storage diseases (LSDs) with predominant neurological
      manifestations. Herein we report the development and characterization of a cell
      model for a rapid neurodegenerative LSDs, globoid-cell leukodystrophy (GLD),
      mostly known as Krabbe disease. GLD is caused by the deficiency of beta
      galactocerebrosidase (GALC), a lysosomal enzyme that hydrolyzes two
      glycosphingolipids, psychosine and galactosylceramide. Unfortunately, the
      available culture fibroblasts from GLD patients consist of a limited research
      tool as these cells fail to accumulate psychosine, the central pathogenic
      glycosphingolipid in this LSD that results in severe demyelination. Firstly, we
      obtained brain samples from the Twitcher (Twi) mice (GALC(twi/twi)), the natural
      mouse model with GALC deficiency. We immortalized the primary neuroglial cultured
      cells with SV40 large T antigen, generating the 145M-Twi and the 145C-Wt cell
      lines from the Twi and control mice, respectively. Both cell lines expressed
      specific oligodendrocyte markers including A2B5 and GalC. The 145M-Twi cells
      showed biochemical and cellular disturbances related to GLD neuropathogenesis
      including remarkable caspase-3 activation, release of cytochrome C into the
      cytosol and expansion of the lysosomal compartment. Under treatment with
      glycosphingolipids, 145M-Twi cells showed increased LC3B levels, a marker of
      autophagy. Using the LC-MS/MS method that we developed, the 145M-Twi cells showed
      significantly higher levels of psychosine. The 145M-Twi and 145C-Wt lines allowed
      the development of a robust throughput LC-MS/MS assay to measure cellular
      psychosine levels. In this throughput assay, l-cycloserine showed to
      significantly reduce the 145M-Twi cellular levels of psychosine. The established
      145M-Twi cells are powerful research tools to investigate the neurologically
      relevant pathogenic pathways as well as to develop primary screening assays for
      the identification of therapeutic agents for GLD and potentially other
      glycosphingolipid disorders. 

PMID- 24094554
TI  - Achieving high-value cardiac imaging: challenges and opportunities.
AB  - Cardiac imaging is under intense scrutiny as a contributor to health care costs,
      with multiple initiatives under way to reduce and eliminate inappropriate
      testing. Appropriate use criteria are valuable guides to selecting imaging
      studies but until recently have focused on the test rather than the patient.
      Patient-centered means are needed to define the true value of imaging for
      patients in specific clinical situations. This article provides a definition of
      high-value cardiac imaging. A paradigm to judge the efficacy of echocardiography
      in the absence of randomized controlled trials is presented. Candidate clinical
      scenarios are proposed in which echocardiography constitutes high-value imaging,
      as well as stratagems to increase the likelihood that high-value cardiac imaging
      takes place in those circumstances. 

PMID- 24094555
TI  - Comments on Mahaluxmivala et al. "Ilizarov external fixator: Acute shortening and
      lengthening versus bone transport in the management of tibial non-unions".

PMID- 24094556
TI  - Diagnosing lymphoma and leukaemia - when all cells are created equal.

PMID- 24094557
TI  - Statistics: more regression models.
AB  - In a previous article, we tackled the question "How are we related?" for the
      simple case of one explanatory variable or covariate. Now we can move onto a
      natural extension, with still only one response variable, but more than one
      explanatory variable. 

PMID- 24094558
TI  - Comment on "Biokinetics and bacterial communities of propionate oxidizing
      bacteria in phased anaerobic sludge digestion systems" by M. Zamanzadeh, W.J.
      Parker, Y. Verastegui, J.D. Neufeld [Water Res. (2013)].

PMID- 24094559
TI  - Systolic function reserve using two-dimensional strain imaging in hypertrophic
      cardiomyopathy: comparison with essential hypertension.
AB  - BACKGROUND: Although patients with hypertrophic cardiomyopathy (HCM) have normal
      ejection fractions at rest, the investigators hypothesized that these patients
      have differentially abnormal systolic function reserves, limiting their exercise
      capacity compared with patients with hypertension (HTN). METHODS: Forty patients
      with HCM (mean age, 39.1 +/- 12 years), 20 patients with HTN with LVH, and 33
      healthy individuals underwent resting and peak exercise echocardiography using
      two-dimensional strain imaging. Peak longitudinal systolic strain (epsilonsys)
      and strain rate were measured in apical views. Circumferential epsilonsys and
      left ventricular (LV) twist were analyzed from short-axis views. LV systolic
      dyssynchrony was measured from regional longitudinal strain curves as the
      standard deviation of time to peak strain (time from the beginning of the Q wave
      on electrocardiography to peak epsilonsys) between 12 segments. The differences
      between resting and peak exercise values were analyzed, and functional reserve
      was calculated as the difference divided by the resting value. RESULTS: In
      patients with HCM, resting values for longitudinal epsilonsys, systolic strain
      rate, early diastolic strain rate, and atrial diastolic strain rate were
      significantly lower, while circumferential epsilonsys and twist were higher,
      compared with patients with HTN and controls (P < .0001). Functional systolic
      reserve increased during exercise in controls (17 +/- 6%), increased to a lesser
      extent in patients with HTN (10 +/- 16%), and was markedly attenuated in patients
      with HCM (-23 +/- 28%) (P < .001). At peak exercise, even with augmented
      circumferential epsilonsys and twist in patients with HCM (P < .01) compared with
      those with HTN, both remained lower than in controls (P < .001). LV dyssynchrony
      was amplified during exercise in patients with HCM compared with those with HTN
      (P < .001). Within the entire population, exercise capacity was clearly
      correlated with systolic functional reserve. However when taken separately, it
      was mainly related to resting LV dyssynchrony and diastolic function in patients
      with HCM, whereas it was linked to age and LV wall thickness in those with HTN.
      CONCLUSIONS: Patients with HCM have significantly limited systolic function
      reserve and more dynamic dyssynchrony with exercise compared with those with HTN.
      Two-dimensional strain imaging during stress may provide a new and reliable
      method to identify patients at higher cardiovascular risk.

PMID- 24094560
TI  - Left atrial enlargement and reduced atrial compliance occurs early in Fabry
      cardiomyopathy.
AB  - BACKGROUND: Fabry disease is associated with left ventricular hypertrophy (LVH)
      and myocardial fibrosis. The aim of this study was to evaluate left atrial (LA)
      size and function using tissue Doppler-derived strain in patients with Fabry
      disease. METHODS: Echocardiography was performed in 33 Fabry patients (14 without
      LVH, 19 with LVH) before commencement of enzyme replacement therapy, and results
      were compared with those from age-matched and gender-matched controls (n=28 and
      n=38, respectively). Atrial strain and strain rate were measured from four
      segments in the apical four-chamber and two-chamber views of the LA, and global
      values were calculated. Systolic strain, systolic strain rate, early diastolic
      strain rate, and late diastolic strain rate were measured. Phasic LA volumes and
      fractions were calculated. Mitral inflow and tissue Doppler E' velocities were
      used to estimate left ventricular (LV) diastolic function. RESULTS: LA volume was
      increased in Fabry patients, even in the absence of LVH. Importantly, diastolic
      function was normal in this subgroup without LVH, with E' velocities similar to
      those in controls. LA systolic strain and early diastolic strain rate were
      selectively reduced in Fabry patients with LVH and reflect reductions in LA and
      LV relaxation, respectively, consequent to increased LV mass. However,
      independent of LVH, both Fabry groups had significant reductions in systolic
      strain rate and increased LA stiffness index. CONCLUSIONS: Fabry disease is
      associated with LA enlargement and reduced atrial compliance that occurs before
      the development of LVH. This suggests that Fabry cardiomyopathy may not only
      cause ventricular hypertrophy and fibrosis but also alters atrial myocardial
      properties early in the disease process. Consequently, measurements of LA size
      and function may be useful in the early diagnosis of Fabry disease, before the
      development of LVH.

PMID- 24094561
TI  - The biophysical properties of the aorta are altered following Kawasaki disease.
AB  - BACKGROUND: The long-term sequelae of Kawasaki disease (KD) are based on the
      coronary complications. Because KD causes generalized vasculitis, with documented
      aneurysms in the femoral, iliac, renal, axillary, and brachial arteries, the aim
      of this study was to assess the biophysical properties of the aorta (BPA) after
      KD. The BPA are biometric measurements representing vascular structural and
      dynamic changes in response to cardiac work. METHODS: Anthropometric and
      echocardiographic measurements of the aorta in a series of patients with KD were
      compared with those of healthy subjects. The BPA were calculated noninvasively by
      extrapolating previously validated equations that were conceived for invasive
      measurements. Because BPA vary with body habitus, control subjects were used to
      normalize BPA parameters for height to compute BPA Z-score equations. RESULTS:
      Between June 2007 and February 2010, BPA were recorded in 57 patients with KD >1
      year after the onset of the disease, 45 without and 12 with coronary artery
      sequelae. The mean intervals between the acute onset of KD and enrollment were
      10.0 +/- 5.0 and 5.8 +/- 4.5 years for patients with and without coronary artery
      sequelae, respectively (P = .008). Patients with KD with coronary artery sequelae
      had significantly altered Z scores of aortic diameter modulation, Peterson's
      elastic modulus, and beta stiffness index (P = .001-.016). Patients with KD
      without coronary artery sequelae also exhibited altered elasticity, stiffness,
      and pulse-wave velocity (P = .001-.026). CONCLUSIONS: Altered BPA after KD are
      detectible despite apparent resolution of acute vasculitis. Future directions
      toward determining multilevel and multilayer vascular impact, including vascular
      autonomous homeostasis, require thorough investigation.

PMID- 24094562
TI  - A clinical evaluation of the ProSeal laryngeal mask airway with a Coopdech
      bronchial blocker for one-lung ventilation in adults.
AB  - OBJECTIVE: To compare the effects of one-lung ventilation (OLV) offered by
      ProSeal laryngeal mask airway (PLMA) or endotracheal tube (ETT) with Coopdech
      bronchial blocker (BB) in adult patients undergoing thoracoscopic procedures, and
      also to evaluate the feasibility and security of application of PLMA with
      Coopdech BB for OLV. DESIGN: Prospective, randomized study. SETTING: A local
      hospital. PARTICIPANTS: One-hundred adult patients undergoing thoracoscopic
      procedures. INTERVENTIONS: PLMA with Coopdech BB (group PLMA-BB, n=50) or ETT
      with Coopdech BB (group ETT-BB, n=50) was used for OLV. MEASUREMENTS AND MAIN
      RESULTS: There were no differences between the groups in terms of time of OLV,
      time of correct placement of the BB, or cases of BB dislodgement. Forty-seven
      patients succeeded in OLV in the PLMA-BB group (94%), all patients succeeded in
      OLV in the ETT-BB group (100%), and there was no significant difference in
      success rate between groups (p>0.05). Arterial oxygen tension, end-expiration
      tidal volume, and peak airway pressure showed no statistical difference in TLV or
      30 minutes after the initiation of OLV between 2 groups (p>0.05). CONCLUSION: The
      combined use of PLMA and Coopdech BB in adult patients can achieve adequate OLV
      for brief thoracoscopic procedures.

PMID- 24094563
TI  - CASE 10--2014 Eisenmenger syndrome: close the hole?

PMID- 24094564
TI  - Predictors of postoperative atrial fibrillation in patients with coronary artery
      disease undergoing cardiopulmonary bypass: a possible role for myocardial
      ischemia and atrial inflammation.
AB  - OBJECTIVE: To evaluate the preoperative presence of C-reactive protein (CRP) and
      troponin T(hs-TnT) in patients with coronary artery disease (CAD) undergoing
      cardiopulmonary bypass (CPB) in order to better clarify the role of atrial
      inflammation and/or myocardial ischemia in the development of postoperative
      atrial fibrillation (POAF). DESIGN: Prospective, nonrandomized study. SETTING:
      University hospital. PARTICIPANTS: Thirty-eight consecutive ischemic patients
      admitted to the authors' hospital for CAD undergoing elective on-pump coronary
      artery bypass grafting (CABG). INTERVENTION: Elective on-pump CABG. MEASUREMENTS
      AND MAIN RESULTS: Peripheral blood samples were collected from all patients
      before and 24 hours after CABG to assess high sensitive (hs)-CRP and troponin T
      (hs-TnT) levels. The patients' heart rhythm was monitored by continuous ECG
      telemetry. Biopsies from the right atrial appendage were obtained at the
      beginning of the CABG procedure in order to perform immunohistochemistry for CRP
      and reverse transcription polymerase chain reaction for CRP mRNA expression.
      Fourteen patients out of 38 (36%) developed POAF. Atrial CRP was found in 31
      patients (82%), 10 with POAF and 21 with sinus rhythm (71% v 87% respectively, p
      = ns). None of the atrial samples was positive for CRP mRNA. Atrial CRP did not
      correlate with serum hs-CRP levels and with occurrence of POAF, but with the
      incidence of diabetes (p = 0.010). Postoperative hs-TnT levels, but not hs-CRP
      levels, were identified as the only predictor of POAF occurrence (p = 0.016).
      CONCLUSIONS: In patients undergoing CABG, neither peripheral nor tissue
      preoperative CRP levels, but only postoperative hs-TnT levels, correlated with
      POAF, suggesting the primary role of an ischemic trigger of atrial fibrillation.

PMID- 24094566
TI  - CASE 11--2014. Successful open repair of an extensive descending thoracic aortic
      aneurysm in a complex patient.

PMID- 24094565
TI  - Monitoring of anesthetic depth during surgical correction of acquired valvular
      disorders: single center, randomized trial.
AB  - OBJECTIVE: The authors' primary objective was to test the hypothesis that
      Cerebral State Index (CSI)-guided control of anesthetic depth might reduce the
      consumption of anesthetics and shorten the duration of ICU and hospital stays
      after surgical correction of combined valve disorders. DESIGN: Single center,
      randomized trial. SETTING: City Hospital Number 1 of Arkhangelsk, Russian
      Federation. PARTICIPANTS: Fifty adult patients with combined valve disorders
      requiring surgical correction. INTERVENTIONS: The patients were randomized into 2
      groups. In the CSI group, anesthetic depth was monitored, and the rate of
      infusion of propofol was titrated to maintain the depth of anesthesia
      corresponding to a CSI of 40-60. In the control group, the depth of anesthesia
      was monitored clinically, and the dosage of propofol was administered according
      to the recommendations of the manufacturer. MEASUREMENTS AND MAIN RESULTS: All
      patients received standard perioperative monitoring. Consumption of anesthetics
      and length of ICU and hospital stays were recorded. Preoperative patient
      characteristics did not differ significantly between the groups. In the CSI
      group, average intraoperative doses of midazolam and propofol were reduced by 41%
      and 19%, respectively (p<0.01). Maintenance of anesthesia guided by CSI shortened
      the time until fit for ICU discharge by 50% and reduced the lengths of ICU and
      postoperative hospital stays by 35% and 25%, respectively (p< 0.05). CONCLUSIONS:
      Monitoring of anesthetic depth reduces the requirements for midazolam and
      propofol, resulting in a faster recovery and a shorter postoperative ICU and
      hospital stay after surgical correction of combined valve disorders.

PMID- 24094567
TI  - A brief psychological intervention to improve adherence in type 2 diabetes.
AB  - OBJECTIVE: Diabetes perceptions, acceptance and treatment motivation are
      changeable factors of adherence. This study aimed to test the effects of brief
      psychological interventions based on diabetes threat and mastery perceptions in
      terms of adherence, acceptance and motivation. Physicians may find such
      interventions useful during a 15-minute consultation with diabetes patients.
      RESEARCH DESIGN AND METHODS: This randomized controlled study included 80
      patients with type 2 diabetes, recruited from the hospital diabetes department,
      who were randomly assigned to four intervention groups based on autobiographical
      recall. Those in the two intervention groups were asked to recall diabetic events
      based on mastery and threat perceptions, respectively, whereas those in the two
      control groups recalled non-diabetic events based on positive and negative
      emotions, respectively. Following this, all participants completed validated self
      questionnaires assessing diabetes perceptions, acceptance, treatment motivation
      and adherence. RESULTS: Patients in the threat group reported less adherence
      (P<0.01) and less avoidance (P<0.05), and perceived diabetes as less threatening
      (P<0.05) than those in the mastery group. Similar results were obtained when the
      threat group was compared with its matched negative-emotion control group
      (P<0.05, P<0.05 and P=0.087, respectively). Patients in the mastery group
      reported feeling a stronger sense of mastery (P<0.05) than those in their
      positive-emotion control group and greater treatment acceptance than those in the
      threat group (P<0.01). CONCLUSION: Contrary to conventional medical belief,
      discussing threatening personal events with patients can yield positive results.
      Health professionals should take threat and mastery perceptions of diabetes into
      account during regular consultations with a view to improving treatment
      acceptance and adherence. With this brief intervention of type 2 diabetes
      patients, it was also more effective to alleviate their emotional difficulties
      than to enhance their perception of mastery.

PMID- 24094569
TI  - Type I complex regional pain syndrome.
AB  - First described by Ambroise Pare in the mid-17th century complex, regional pain
      syndrome (CRPS) can be defined as an articular and periarticular pain syndrome
      associated with vasomotor deregulation triggered by various stresses with no
      relationship between the intensity of the initial injury and severity of the
      continuing pain. Several names have been given to Type 1 complex regional pain
      syndrome (CRPS-I): causalgia, reflex sympathetic dystrophy, shoulder-hand
      syndrome and algodystrophy. The reported incidence of CRPS-I is about 25 per
      100,000. Predisposing factors are tobacco consumption and being female (W/M
      ratio=4). Although all the limbs can be affected, the upper limb is by far the
      most affected. CRPS-I is a classic complication of distal radius fractures (4
      37%) and carpal tunnel surgery (2-4%). Early diagnosis and management are the
      most important elements of treatment because this syndrome has a long and
      disabling course. Some of the proposed treatments include NSAIDs, antidepressants
      and anticonvulsants. The latter, despite their good analgesic effects, do not
      cure CRPS-I. In select cases, a surgical procedure aiming at removing a
      nociceptive stimulus can lead to spectacular improvements.

PMID- 24094568
TI  - A meta-analysis of the relationship between antidepressant use in pregnancy and
      the risk of preterm birth and low birth weight.
AB  - OBJECTIVES: To examine the relationship between antidepressant use in pregnancy
      and low birth weight (LBW) and preterm birth (PTB). DATA SOURCES AND STUDY
      SELECTION: We searched English and non-English language articles via PubMed,
      CINAHL and PsychINFO (from their start dates through December 1st, 2012). We used
      the following keywords and their combinations: antidepressant, selective
      serotonin reuptake inhibitor (SSRI), pregnancy, antenatal, prenatal, birthweight,
      birth weight, preterm, prematurity, gestational age, fetal growth restriction,
      intrauterine growth restriction, and small-for-gestational age. Published studies
      were considered eligible if they examined exposure to antidepressant medication
      use during pregnancy and reported data on at least one birth outcome of interest:
      PTB (<37 weeks gestation) or LBW (<2500 g). Of the 222 reviewed studies, 28
      published studies met the selection criteria. DATA EXTRACTION: Two authors
      independently extracted study characteristics from eligible studies. RESULTS:
      Using random-effects models, antidepressant use in pregnancy was significantly
      associated with LBW (RR: 1.44, 95% confidence interval (CI): 1.21-1.70) and PTB
      (RR: 1.69, 95% CI: 1.52-1.88). Studies varied widely in design, populations,
      control groups and methods. There was a high level of heterogeneity as measured
      by I2 statistics for both outcomes examined. The relationship between
      antidepressant exposure in pregnancy and adverse birth outcomes did not differ
      significantly when taking into account drug type (SSRI vs. other or mixed) or
      study design (prospective vs. retrospective). There was a significant association
      between antidepressant exposure and PTB for different types of control status
      used (depressed, mixed or nondepressed). CONCLUSIONS: Antidepressant use during
      pregnancy significantly increases the risk for LBW and PTB.

PMID- 24094570
TI  - [Neurotization of the deep branch of ulnar nerve and the thenar branch of median
      nerve with the pronator quadratus branch of anterior interosseous nerve by end-to
      side transfer. An anatomic study].
AB  - Proximal or middle lesions of median or ulnar nerves are responsible for a great
      loss of hand motor function. Neurotization of either deep ulnar branch of ulnar
      nerve (DBUN) or recurrent (thenar) branch of median nerve (RBMN) with the nerve
      to quadratus pronator (NPQ) from the anterior interosseous nerve (AION) could
      reduce length of axonal growth and therefore the reinnervation lead-time of hand
      intrinsic muscles. We studied the anatomy of these three nerves, to help surgeon
      choosing his (her) technique and approach. Twenty-three cadaver forearms were
      dissected. End-to-side sutures were performed to mimic these neurotizations.
      Distances between nerve sutures and ulnar styloid process (USP) or
      trapeziometacarpal joint (TM) were measured. All the sutures but one RBMN could
      be done. On average sutures were distant from USP by 44+/-17mm (neurotization of
      DBUN), from TM by 62+/-15mm (neurotization of RBMN). Knowledge of average
      distance to perform these neurotizations should allow choosing the best reduced
      approach of RBMN and DBUN. Neurotizations of DBNU and RBMN with NPQ were feasible
      for lesions located at 6.1cm upstream USP and 7.7cm upstream TM, respectively.
      End-to-side sutures remain to be clinically evaluated. 

PMID- 24094572
TI  - On the possible benefits of a hybrid VMAT technique in the treatment of non-small
      cell lung cancer.
AB  - To assess, using clinical cases, the potential of a hybrid technique for the
      treatment of non-small cell lung cancer (NSCLC)-blending volumetric-modulated arc
      therapy (VMAT) and conformal radiation therapy (CRT) fields, and to consider
      potential issues with implementation of such a technique. Eight clinical cases
      already treated with CRT were used for a planning study comparing target coverage
      and organs at risk (OAR) sparing between CRT and hybrid VMAT (VMATh). Quality
      assurance (QA) implications of the resultant hybrid plans are discussed. The
      hybrid technique resulted in superior target conformity or improved sparing of
      OAR or both. The hybrid technique shows promise, but the QA implications of
      motion at treatment need careful consideration. 

PMID- 24094571
TI  - A technique using 99mTc-mebrofenin SPECT for radiotherapy treatment planning for
      liver cancers or metastases.
AB  - Radiotherapy or stereotactic body radiosurgery (SBRT) requires a sufficient
      functional liver volume to tolerate the treatment. The current study extended the
      work of de Graaf et al. (2010) [3] on the use of (99m)Tc-mebrofenin imaging for
      presurgery planning to radiotherapy planning for liver cancer or metastases.
      Patient was immobilized and imaged in an identical position on a single-photon
      emission computed tomography/computed tomography (SPECT-CT) system and a
      radiotherapy simulation CT system. (99m)Tc-mebrofenin SPECT was registered to the
      planning CT through image registration of noncontrast CT from SPECT-CT system to
      the radiotherapy planning CT. The voxels with higher uptake of (99m)Tc-mebrofenin
      were transferred to the planning CT as an avoidance structure in optimizing a 2
      arc RapidArc plan for SBRT delivery. Excellent dose coverage to the target and
      sparing of the healthy remnant liver volume was achieved. This report illustrated
      a procedure for the use of (99m)Tc-mebrofenin SPECT for optimizing radiotherapy
      for liver cancers and metastases. 

PMID- 24094573
TI  - Surgical management of node-positive prostate cancer: perspectives from breast
      oncology.

PMID- 24094574
TI  - No androgen withdrawal syndrome for enzalutamide: a report of disease dynamics in
      the postchemotherapy setting.

PMID- 24094575
TI  - The new promise of FACBC position emission tomography/computed tomography in the
      localization of disease relapse after radical treatment for prostate cancer: are
      we turning to the right radiotracer?

PMID- 24094576
TI  - Predicting survival of patients with node-positive prostate cancer following
      multimodal treatment.
AB  - BACKGROUND: According to the TNM staging system, patients with prostate cancer
      (PCa) with lymph node invasion (LNI) are considered a single-risk group. However,
      not all LNI patients share the same cancer control outcomes. OBJECTIVE: To
      develop and internally validate novel nomograms predicting cancer-specific
      mortality (CSM)-free rate in pN1 patients. DESIGN, SETTING, AND PARTICIPANTS: We
      evaluated 1107 patients with pN1 PCa treated with radical prostatectomy, pelvic
      lymph node dissection, and adjuvant therapy at two tertiary care centers between
      1988 and 2010. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: Univariable and
      multivariable Cox regression models tested the relationship between CSM and
      patient clinical and pathologic characteristics, which consisted of prostate
      specific antigen (PSA) value, pathologic Gleason score, pathologic tumor stage,
      status of surgical margins, number of positive lymph nodes, and status of
      adjuvant therapy. A Cox regression coefficient-based nomogram was developed and
      internally validated. RESULTS AND LIMITATIONS: All 1107 patients received
      adjuvant hormonal therapy (aHT). Additionally, 35% of patients received adjuvant
      radiotherapy (aRT). The 10-yr CSM-free rate was 84% in the entire cohort and 87%
      in patients treated with aRT plus aHT versus 82% in patients treated with aHT
      alone (p=0.08). At multivariable analyses, PSA value, pathologic Gleason score,
      pathologic tumor stage, surgical margin status, number of positive lymph nodes,
      and aRT status were statistically significant predictors of CSM (all p <= 0.04).
      Based on these predictors, nomograms were developed to predict the 10-yr CSM-free
      rate in the overall patient population and in men with biochemical recurrence.
      These models showed high discrimination accuracy (79.5-83.3%) and favorable
      calibration characteristics. These results are limited by their retrospective
      nature. CONCLUSIONS: Some patients with pN1 PCa have favorable CSM-free rates at
      10 yr. We developed and internally validated the first nomograms that allow an
      accurate prediction of the CSM-free rate in these patients at an individual
      level.

PMID- 24094577
TI  - Identification of a novel missense (C7W) mutation of SOD1 in a large familial
      amyotrophic lateral sclerosis pedigree.
AB  - Mutations of Cu-Zn superoxide dismutase (SOD1) have rarely been identified in
      Chinese patients with amyotrophic lateral sclerosis (ALS). We recently initiated
      a program to screen mutations of SOD1, TARDBP, and C9orf72 genes, the most
      commonly mutated genes in ALS patients in Western countries, in Chinese ALS
      patients. In this study, we report a novel missense SOD1 mutation with a
      substitution of tryptophan for cysteine at the seventh amino acid (p.C7W,
      traditionally named p.C6W) based on HUGO Gene Nomenclature in a familial ALS
      pedigree. We also found that the activities of SOD1 were significantly decreased
      in the C7W patient and the carriers of the family, compared with the SOD1
      activities of normal family members. Compared with reported C7G and C7S patients,
      analysis of phenotype revealed relatively mild disease phenotypes in C7W
      patients, which is correlated with less deteriorated alteration in protein
      structure. Like those of many other familial ALS families, variable clinical
      phenotypes in the C7W intrafamily suggest that potential genetic modifiers may
      contribute to this disease.

PMID- 24094578
TI  - Age-related differences in the neural correlates mediating false recollection.
AB  - The current study investigated the effects of aging on the neural basis
      underlying true and false recollection. Although older adults, compared with
      younger adults, exhibited equivalent rates of true recollection, age differences
      in true recollection showed a pattern of activity commonly found among previous
      memory studies (e.g., age-related decreases in occipital and increases in
      prefrontal cortices), suggesting reduced retrieval of perceptual details
      associated with encoding items and a greater reliance on top-down compensatory
      processing. With regard to false recollection, older adults exhibited
      significantly greater false recollection yet did not exhibit increased neural
      processing. They did exhibit decreased activity in prefrontal, parahippocampal
      gyrus, and occipitoparietal cortex, suggesting a reduced reliance on
      reconstruction processes mediating false recollection in young. An individual
      differences analysis in older adults found false recollection rates predicted
      activity in several regions. including bilateral middle/superior temporal gyrus.
      Taken together, these results indicate that increases in false recollection in
      aging may be mediated by reduced access to encoding-related details as well as
      reliance on semantic gist and familiarity-related neural activity. 

PMID- 24094579
TI  - Melanocortins protect against progression of Alzheimer's disease in triple
      transgenic mice by targeting multiple pathophysiological pathways.
AB  - Besides specific triggering causes, Alzheimer's disease (AD) involves
      pathophysiological pathways that are common to acute and chronic
      neurodegenerative disorders. Melanocortins induce neuroprotection in experimental
      acute neurodegenerative conditions, and low melanocortin levels have been found
      in occasional studies performed in AD-type dementia patients. Here we
      investigated the possible neuroprotective role of melanocortins in a chronic
      neurodegenerative disorder, AD, by using 12-week-old (at the start of the study)
      triple-transgenic (3xTg-AD) mice harboring human transgenes APPSwe, PS1M146V, and
      tauP301L. Treatment of 3xTg-AD mice, once daily until the end of the study (30
      weeks of age), with the melanocortin analog [Nle(4),D-Phe(7)]-alpha-melanocyte
      stimulating hormone (NDP-alpha-MSH) reduced cerebral cortex/hippocampus
      phosphorylation/level of all AD-related biomarkers investigated (mediators of
      amyloid/tau cascade, oxidative/nitrosative stress, inflammation, apoptosis),
      decreased neuronal loss, induced over-expression of the synaptic activity
      dependent gene Zif268, and improved cognitive functions, relative to saline
      treated 3xTg-AD mice. Pharmacological blockade of melanocortin MC4 receptors
      prevented all neuroprotective effects of NDP-alpha-MSH. Our study identifies, for
      the first time, a class of drugs, MC4 receptor-stimulating melanocortins, that
      are able to counteract the progression of experimental AD by targeting
      pathophysiological mechanisms up- and down-stream of beta-amyloid and tau. These
      data could have important clinical implications.

PMID- 24094580
TI  - beta-amyloid impairs the regulation of N-methyl-D-aspartate receptors by glycogen
      synthase kinase 3.
AB  - Accumulating evidence suggests that glycogen synthase kinase 3 (GSK-3) is a
      multifunctional kinase implicated in Alzheimer's disease (AD). However, the
      synaptic actions of GSK-3 in AD conditions are largely unknown. In this study, we
      examined the impact of GSK-3 on N-methyl-D-aspartate receptor (NMDAR) channels,
      the major mediator of synaptic plasticity. Application of GSK-3 inhibitors or
      knockdown of GSK-3 caused a significant reduction of NMDAR-mediated ionic and
      synaptic current in cortical neurons, whereas this effect of GSK-3 was impaired
      in cortical neurons treated with beta-amyloid (Abeta) or from transgenic mice
      overexpressing mutant amyloid precursor protein. GSK-3 activity was elevated by
      Abeta, and GSK-3 inhibitors failed to decrease the surface expression of NMDA
      receptor NR1 (NR1) and NR1/postsynaptic density-95 (PSD-95) interaction in
      amyloid precursor protein mice, which was associated with the diminished GSK-3
      regulation of Rab5 activity that mediates NMDAR internalization. Consequently,
      GSK-3 inhibitor lost the capability of protecting neurons against N-methyl-D
      aspartate-induced excitotoxicity in Abeta-treated neurons. These results have
      provided a novel mechanism underlying the involvement of GSK-3 in AD. 

PMID- 24094582
TI  - Age-related deterioration of the representation of space in human auditory
      cortex.
AB  - One of the principal auditory disabilities associated with older age is
      difficulty in locating and tracking sources of sound. This study investigated
      whether these difficulties are associated with deterioration in the
      representation of space in the auditory cortex. In psychophysical tests, half of
      a group of older (>60 years) adults displayed spatial acuity similar to that of
      young adults throughout the frontal horizontal plane. The remaining half had
      considerably poorer spatial acuity at the more peripheral regions of frontal
      space. Computational modeling of electroencephalographic responses to abrupt
      location shifts demonstrated marked differences in the spatial tuning of
      populations of cortical neurons between the older adults with poor spatial acuity
      on the one hand, and those with good spatial acuity, as well as young adults, on
      the other hand. In those with poor spatial acuity, cortical responses contained
      little information with which to distinguish peripheral locations. We demonstrate
      a clear link between neural responses and spatial acuity measured behaviorally,
      and provide evidence for age-related changes in the coding of horizontal space. 

PMID- 24094581
TI  - Effects of cerebrospinal fluid proteins on brain atrophy rates in cognitively
      healthy older adults.
AB  - Biomarkers associated with Alzheimer's disease (AD)-like brain atrophy in healthy
      individuals may identify mechanisms involved in early stage AD. Aside from
      cerebrospinal fluid (CSF) beta-amyloid42 (Abeta42) and tau, no studies have
      tested associations between CSF proteins and AD-like brain atrophy. We studied 90
      healthy elders, who underwent lumbar puncture at baseline, and serial magnetic
      resonance imaging scans for up to 4 years. We tested statistical effects of
      baseline CSF proteins (N = 70 proteins related to Abeta42-metabolism, microglial
      activity, and synaptic/neuronal function) on atrophy rates in 7 AD-related
      regions. Besides the effects of Abeta42 and phosphorylated tau (P-tau) that were
      seen in several regions, novel CSF proteins were found to have effects in
      inferior and middle temporal cortex (including apolipoprotein CIII,
      apolipoprotein D, and apolipoprotein H). Several proteins (including S100beta and
      matrix metalloproteinase-3) had effects that depended on the presence of brain
      Abeta pathology, as measured by CSF Abeta42. Other proteins (including P-tau and
      apolipoprotein D) had effects even after adjusting for CSF Abeta42. The
      statistical effects in this exploratory study were mild and not significant after
      correction for multiple comparisons, but some of the identified proteins may be
      associated with brain atrophy in healthy persons. Proteins interacting with CSF
      Abeta42 may be related to Abeta brain pathology, whereas proteins associated with
      atrophy even after adjusting for CSF Abeta42 may be related to Abeta-independent
      mechanisms. 

PMID- 24094583
TI  - iHammer.

PMID- 24094584
TI  - A four-year follow-up study of physical working conditions and perceived mental
      and physical strain among food industry workers.
AB  - This study hypothesized that in a longitudinal setting deteriorating physical
      working conditions increases the perceived physical and mental strain among food
      processing employees. The study was conducted in 2003 and 2007. It examined 248
      blue-collar workers, all of whom were in the same occupation throughout the
      entire follow-up period. The data were obtained through a structural
      questionnaire distributed to the employees at the workplace. Mental strain had
      increased (7%) significantly among younger employees during the follow-up. The
      changes in mental strain for the younger employees were positively associated
      with the changes in physical strain. The changes in physical strain were also
      significantly associated with the changes in physical working conditions among
      both younger and the older workers. The results of this study partly support the
      study hypothesis, namely that deteriorating physical working condition increases
      physical strain and also increases mental strain, especially among younger
      employees. 

PMID- 24094585
TI  - Human performance under two different command and control paradigms.
AB  - The paradoxical behaviour of a new command and control concept called Network
      Enabled Capability (NEC) provides the motivation for this paper. In it, a
      traditional hierarchical command and control organisation was pitted against a
      network centric alternative on a common task, played thirty times, by two teams.
      Multiple regression was used to undertake a simple form of time series analysis.
      It revealed that whilst the NEC condition ended up being slightly slower than its
      hierarchical counterpart, it was able to balance and optimise all three of the
      performance variables measured (task time, enemies neutralised and attrition).
      From this it is argued that a useful conceptual response is not to consider NEC
      as an end product comprised of networked computers and standard operating
      procedures, nor to regard the human system interaction as inherently stable, but
      rather to view it as a set of initial conditions from which the most adaptable
      component of all can be harnessed: the human. 

PMID- 24094586
TI  - Towards a comprehensive Functional Capacity Evaluation for hand function.
AB  - The aim of this study was to develop a more efficient (i.e. shortened) protocol
      for hand function capacity evaluation and to test the agreement of the protocol
      compared to the original protocol. 643 Healthy subjects performed tests for hand
      function. Agreement between two shortened protocols was compared with an existing
      protocol. The original protocol was performed once and the proposed shortened
      protocol differed in the number of trials which were reduced by statistical
      elimination. Agreement was determined with Intraclass Correlation Coefficients
      (ICC) and Limits of Agreement (LoA). Excellent ICCs (>=0.91) were observed in all
      proposed protocols except for the one trial purdue pegboard test protocol. For
      all tests of hand function, shorter protocols are valid to determine hand
      function. For Tip Pinch Strength testing, Palmar Pinch Strength testing and the
      Purdue Pegboard test, a two-trial protocol is recommended, because the LoA were
      considerable, which could affect decision-making with regards to hand capacity.
      For the Hand Grip strength test, the Key Pinch Strength test and the Complete
      Minnesota Dexterity Test, a one-trial protocol is recommended, because the LoA
      were acceptable. It was concluded that for healthy subjects, this shorter
      protocol is a reliable measure. Further testing of the short form hand FCE
      protocols should be completed on patients with disabling conditions prior to
      widespread use of these protocols among clinical samples. 

PMID- 24094587
TI  - Comments on neonatal hair-Hg and birth weight in China: mercury in rice and fish.

PMID- 24094588
TI  - Exposure assessment and health risk of poly-brominated diphenyl ether (PBDE)
      flame retardants in the indoor environment of elementary school students in
      Korea.
AB  - This study assessed the health risks of elementary school students' exposure to
      PBDEs via different possible pathways in children's facilities. After PBDE
      contamination was measured, exposure was demonstrated to occur through multiple
      routes, including inhalation of indoor dust, dermal contact with products'
      surfaces and children's hands, and incidental dust ingestion. Samples were
      collected from various children's facilities (30 elementary schools, 31 private
      academies, 12 living rooms and bedrooms in houses, 5 public libraries of
      children's literature, and 3 large hypermalls) in summer (Jul-Sep, 2008) and
      winter (Jan-Feb, 2009). The hazard index (HI) was estimated for non-carcinogens
      and PBDEs, such as TeBDE, PeBDE, HxBDE, OcBDE, and DeBDE. PBDEs were detected in
      all floor dust samples, 99% of indoor air samples, 94% of product-wipe samples,
      and 86% of hand wipe samples. The average levels of PBDEs ranged from 0.19 to
      1.06 ng/m(3) in indoor air, 4623 to 6,650 ng/g-dust in floor dust, 0.012 to 0.103
      ng/cm(2) on product surfaces, and 7.89 to 25.38 ng/hand on the surface of
      children's hands. The HI for school children via multimedia and multipathway
      exposure to PBDEs did not exceed 1.0. The exposure to PBDEs at home
      (approximately 80%) was dominant. The contribution rates of PBDE risk were 77%
      and 15% via dust ingestion at home and at elementary school, respectively; thus,
      intake of floor dust was determined to be the primary route of exposure.

PMID- 24094589
TI  - A clinically validated diagnostic second-generation sequencing assay for
      detection of hereditary BRCA1 and BRCA2 mutations.
AB  - Individuals who inherit mutations in BRCA1 or BRCA2 are predisposed to breast and
      ovarian cancers. However, identifying mutations in these large genes by
      conventional dideoxy sequencing in a clinical testing laboratory is both time
      consuming and costly, and similar challenges exist for other large genes, or sets
      of genes, with relevance in the clinical setting. Second-generation sequencing
      technologies have the potential to improve the efficiency and throughput of
      clinical diagnostic sequencing, once clinically validated methods become
      available. We have developed a method for detection of variants based on
      automated small-amplicon PCR followed by sample pooling and sequencing with a
      second-generation instrument. To demonstrate the suitability of this method for
      clinical diagnostic sequencing, we analyzed the coding exons and the intron-exon
      boundaries of BRCA1 and BRCA2 in 91 hereditary breast cancer patient samples. Our
      method generated high-quality sequence coverage across all targeted regions, with
      median coverage greater than 4000-fold for each sample in pools of 24. Sensitive
      and specific automated variant detection, without false-positive or false
      negative results, was accomplished with a standard software pipeline using bwa
      for sequence alignment and samtools for variant detection. We experimentally
      derived a minimum threshold of 100-fold sequence depth for confident variant
      detection. The results demonstrate that this method is suitable for sensitive,
      automatable, high-throughput sequence variant detection in the clinical
      laboratory. 

PMID- 24094590
TI  - Automatic segmentation of cardiac MRI cines validated for long axis views.
AB  - Segmentation of cardiac magnetic resonance imaging is considered an important
      application in clinical practice. An automatic algorithm is proposed for
      segmentation of both endocardial and epicardial boundaries, in long-axis views.
      The data consisted of 126 patients, yielding 1008 traces. Estimated clinical
      parameters were highly correlated to gold standard measurements. The error
      between the automatic tracing and the gold standard was not significantly
      different than the error between two manual observers. In conclusion, a tool for
      segmenting the myocardial boundaries in the long-axis views is proposed, which
      works well, as demonstrated by the validation performed using a clinical dataset.

PMID- 24094591
TI  - Reconstruction of coronary vessels from intravascular ultrasound image sequences
      based on compensation of the in-plane motion.
AB  - A three-dimensional vessel model is reconstructed by fusing the cross-sectional
      information of vascular lumen detected from intravascular ultrasound (IVUS)
      frames with the spatial geometry of the ultrasonic catheter recovered from a pair
      of nearly orthogonal X-ray angiograms. This model is closer to the actual
      morphology than those reconstructed from angiograms or IVUS images alone because
      of the complementarity between angiography and IVUS in imaging coronary vessels.
      This study proposes a method to reconstruct the coronary vessels from an
      electrocardiogram (ECG)-gated IVUS image sequence and simultaneously acquired
      angiograms. The spatial orientation of each cross-section of the vascular lumen
      detected from IVUS frames was determined through quantitatively compensating the
      in-plane rigid motion caused by cardiac cycles. Independent validation of the
      determination of the IVUS spatial orientation with synthetic data was performed.
      A limited validity study including the back-projection validation and morphology
      measures with in vivo image data (five datasets) was performed to evaluate
      quantitatively the reconstruction accuracy. 

PMID- 24094592
TI  - [Negative pressure therapy for the treatment of inguinal lymphatic fistula].

PMID- 24094593
TI  - [Delayed massive hemothorax due to a diaphragmatic laceration associated with
      lower rib fractures. A penetrating injury in blunt trauma].

PMID- 24094594
TI  - [Duodenal perforation associated with taenia saginata infestation].

PMID- 24094595
TI  - [Uterine ishtmique transmural hernia: results of its repair on symptoms and
      fertility].
AB  - OBJECTIVE: To study the effect of the surgical repair (isthmorraphy) of the large
      scar dehiscence after cesarean on symptoms and fertility for women who desire
      pregnancy. PATIENTS AND METHODS: In this retrospective study, 14 symptomatic
      patients, who desire a new pregnancy underwent a surgical repair by laparotomy,
      laparoscopic or vaginal technique. Five women experienced failure of Assistance
      Reproductive Technique (IVF or ICSI) for idiopathic secondary infertility. The
      dehiscent scars were evaluated by ultrasound, hysterography, hysteroscopy and
      magnetic resonance imaging. OUTCOME: Symptoms improvement was found in 92% of
      case. Ten pregnancy (71%) was obtained after surgical repair, 6 spontaneous and 4
      after Assistance Reproductive Technique. Among the 5 women initially followed in
      the reproductive unit, 4 became pregnant, 3 after IVF or ICSI and 1 spontaneous.
      No operative complication occurred. The subsequent pregnancy was unremarkable
      with no uterine rupture. DISCUSSION: Large scar defect after cesarean can take
      shape of a complete absent of the anterior wall of the uterus. No incident has
      been proved in this condition. There is a lack of data concerning these
      isthmocele. The experience of hysteroscopic repair cannot be applied to these
      real large diverticule of the scar cesarean. The results of this study suggest a
      link between the isthmocele and reversible symptoms after surgery. The first
      results concerning the subsequent fertility after surgical repair seem
      interesting CONCLUSION: When a large scare defect (isthmocele) is found in
      symptomatic woman (pelvic pain, bleeding uterine, infertility), a surgical repair
      can be proposed, especially for woman who desire a new pregnancy.

PMID- 24094596
TI  - [Fertility preservation strategies in young women in case of breast cancer or
      hematologic malignancy].
AB  - The incidence of cancer in young patients as well as survival rates is steadily
      increasing. The question of fertility capacity is therefore of great importance
      regarding the quality of life after cancer. According to the ASCO
      recommendations, every patient should be advised about the chemotherapy-induced
      ovarian damage and fertility preservation possibilities. Several options can be
      discussed: embryo and/or oocytes freezing and ovarian tissue cryopreservation.
      Fertility preservation techniques are progressing rapidly but it still remains
      difficult to establish precise flow-charts according to age, marital status,
      type, dose and timing of chemotherapy. 

PMID- 24094597
TI  - Confocal laser endomicroscopy for prediction of disease relapse in ulcerative
      colitis: a pilot study.
AB  - BACKGROUND AND AIMS: Neoangiogenesis and increased endothelial permeability are
      observed as results of chronic intestinal inflammation. However, limited data on
      microvascular and crypt architecture during remission phases is available. The
      aim of this prospective investigator blinded cohort study was to assess crypt and
      microvascular architecture and function in ulcerative colitis by probe based
      confocal laser endomicroscopy; we also evaluated whether these findings may have
      the potential to predict disease relapse. METHODS: 19 ulcerative colitis patients
      in clinical and endoscopic remission and 19 controls were studied. A computer
      based image processing technique was applied to construct 20 mosaicing image sets
      from each subject. Remitting patients were sub-grouped into either inactive or
      quiescent disease according to histology. RESULTS: Pericrypt fluorescence
      (p<0.01), crypt diameter (p<0.05) but not intercrypt distance (p=0.07) were
      significantly increased in ulcerative colitis patients compared to controls.
      Patients with inactive disease showed a significant increase in fluorescence
      leakage (median fluorescence (IQR), 3888 (3560-4240) vs. 2696 (2502-3390),
      p<0.01), crypt diameter (median diameter (IQR), 92.5 (85.5-101) vs. 73 (70-77),
      p<0.05) and intercrypt distance (median distance (IQR), 82.5 (70.5-91.2) vs. 66
      (59.5-73.5), p<0.05) compared to those with quiescent disease. A composite
      outcome score combining fluorescence leakage and crypt diameter was able to
      predict a disease flare during a 12 month follow-up period (p<0.01). CONCLUSIONS:
      In vivo intramucosal changes detected by confocal endomicroscopy in ulcerative
      colitis remittent patients can predict disease relapse. This observation may have
      further implications for disease management and medical treatment.

PMID- 24094598
TI  - A tale of two diseases: the history of inflammatory bowel disease.
AB  - 'Inflammatory bowel disease' (IBD) sounds like a straightforward term - a disease
      of inflammation in the bowel. However, the history of IBD reveals a story of a
      nefariously complex set of idiopathic conditions. IBD defies definition, in part
      because its pathophysiology is not completely understood. For the same reason and
      despite substantial advances in research, IBD also defies cure. At best, IBD can
      be defined as a disease of disruption - disrupted physiology, microbiology,
      immunology and genetics. The term 'IBD' is most often used to describe two
      separate conditions: ulcerative colitis (UC) and Crohn's disease (CD). This paper
      reviews the history of IBD, considering the ever-evolving understanding of both
      UC and CD. Beyond its intrinsic interest, the history of IBD exemplifies a
      pattern that is becoming increasingly familiar in the 21st century - the story of
      a chronic, incurable disease that defies the best efforts to treat it. 

PMID- 24094599
TI  - Cost and quality-adjusted life year differences in the treatment of active
      ulcerative colitis using once-daily 4 g or twice-daily 2g mesalazine dosing.
AB  - BACKGROUND: Improved compliance in active ulcerative colitis (UC) is likely to
      improve healthcare efficiency by reducing time spent in active mild to moderate
      UC state. To establish whether once daily (OD) mesalazine offers economic
      advantages over twice daily (BD) dosing in active UC, we evaluated the outcomes
      and costs of a recently published randomized study. METHODS: A cost-effectiveness
      model with four week Markov cycles was developed to reflect current treatment
      practices in the Netherlands with OD and BD mesalazine for active UC. The health
      service perspective of the Netherlands was reflected in the model and considered
      a 32week time horizon with 4 weekly Markov cycles. Outcomes evaluated in the
      model were time spent in active and remission UC and the corresponding health
      related quality of life associated with different clinical states. This was then
      used to derive quality adjusted life-years (QALYs) at each treatment stage.
      RESULTS: A greater proportion of subjects on 4 g OD achieved remission at weeks 4
      and 8 compared with 2g BD. After 32 weeks the average costs per patient with
      active UC were ?3097 and ?3548 for those treated with OD and BD mesalazine
      respectively, with an average saving of ?451 per patient treated with OD
      mesalazine. The average costs per QALY for OD and BD mesalazine were ?5433 and
      ?6324 for OD and BD, respectively. CONCLUSIONS: Based on the results from a
      single randomized study, OD dosing resulted in a shorter time spent in active UC
      which resulted in lower healthcare costs.

PMID- 24094600
TI  - [Construction of a questionnaire to assess the knowledge of patients on the
      waiting list for liver transplantation: a pilot study].
AB  - OBJECTIVE: To evaluate the suitability of a questionnaire designed to assess the
      knowledge of patients on the waiting list for liver transplantation, through a
      pilot study. METHOD: A descriptive study of the construction of a knowledge
      questionnaire for patients on the waiting list for liver transplantation. This
      study was developed in the liver pre-transplant clinic of the Hospital Clinic of
      Barcelona from October 2011 to April 2012. An initial questionnaire was designed.
      This draft was improved following the recommendations of experts in liver
      transplantation, and after the completion of a preliminary test. The
      questionnaire obtained was applied to 25 patients in the pilot study. The quality
      of the questions was measured using the discrimination index and the index of
      attraction. The construct was assessed by principal component analysis and factor
      analysis. RESULTS: The questionnaire consisted of 36 items (questions). Of these,
      31 are independent. The discrimination index identified only 4 questions with a
      good (desired information ai=.30) and very good (list exclusion ai=.40, list and
      time on list ai=.58) level of discrimination. The remaining questions had a poor
      or insufficient level of discrimination (ai<29). The principal component analysis
      and factor analysis indicated that the questions related to the disease (10) and
      the waiting list (4) were essential in the questionnaire, and the questions
      related to demographic data (7) and the therapeutic regimen (8) should be
      eliminated. CONCLUSIONS: The questionnaire obtained needs to be modified to
      assess the knowledge of patients on waiting list for liver transplantation.

PMID- 24094601
TI  - [Descriptive study of ambulatory blood pressure monitoring in the Primary Care
      Nursing clinic].
AB  - OBJECTIVE: To analyze the clinical characteristics and the circadian patterns of
      patients who received ambulatory blood pressure monitoring (ABPM) by a Primary
      Care Team. METHOD: A descriptive, observational, cross-sectional study at
      community level. People older than 18 years on ABPM (2007-2011). VARIABLES:
      demographic, cardiovascular disease, diabetes mellitus, cardiovascular risk
      factors, any type of arterial hypertension and circadian pattern. Intruments of
      measurement: 2 validated instruments with comparable results were used.
      PROCEDURE: The instruments for ABPM were placed during the nursing visit. The
      instruments were then removed after 24h, and the data was retrieved and recorded
      in the computerized clinical history. RESULTS: A total of 326 people were
      studied, with a mean age of 60.53+/-12.96 years, of whom 56.7% were male.
      According to ABPM the patient results showed that: 38.5% had "white coat"
      arterial hypertension, 36.2% were classified as poorly controlled arterial
      hypertension, 17.2% had masked hypertension, and 8% with isolated hypertension.
      Dipper circadian patterns were present in 39.6% of patients and non- dipper in
      60.4%. CONCLUSIONS: ABPM allows to Primary Health Care professionals to check the
      actual situation of the blood pressure over 24h and analyze the circadian
      pattern. In clinical practice this involves having a comprehensive care strategy
      on life style, as well as adherence to treatment.

PMID- 24094602
TI  - Lobectomy and postoperative thromboprophylaxis with enoxaparin improve blood
      hypercoagulability in patients with localized primary lung adenocarcinoma.
AB  - BACKGROUND: Patients with lung adenocarcinoma undergoing surgery are in high risk
      for VTE and receive routine post-operative thromboprophylaxis with LWMH. AIM: We
      investigated markers of hypercoagulability in patients with primary localized
      adenocarcinoma and the modifications induced by lobectomy and postoperative
      administration of enoxaparin. MATERIALS AND METHODS: Patients suffering from
      localised primary lung adenocarcinoma (n=15) scheduled for lobectomy were
      studied. The control group consisted of 15 healthy age and sex-matched
      individuals. Blood was collected before anaesthesia induction and after surgery,
      at several intervals until the 7th post-operative day. Samples were assessed for
      thrombin generation, phosphatidylserin expressing platelet derived microparticles
      expressing (Pd-MP/PS(+)), tissue factor activity (TFa), FVIIa and TFPI levels,
      procoagulant phospholipid dependent clotting time and anti-Xa activity. RESULTS:
      At baseline, patients showed increased thrombin generation and Pd-MP/PS(+). After
      lobectomy thrombin generation significantly decreased. Administration of
      enoxaparin attenuated thrombin generation. In about 50% of samples collected post
      operatively an increase of thrombin generation occurred despite the presence of
      the expected anti-Xa activity in plasma. At the 7th post-operative day, 3 out of
      15 patients showed a significant increase of thrombin generation. CONCLUSION: In
      patients with localized lung adenocarcinoma, hypercoagulability is characterized
      by high thrombin generation and increased concentration of Pd-MP/PS(+). Tumor
      mass resection is related with attenuation of thrombin generation, which is
      inhibited by postoperative thromboprophylaxis with enoxaparin. The response to
      enoxaparin is not predicted by the concentration of the anti-Xa activity in
      plasma. The assessment of thrombin generation during prophylaxis with enoxaparin
      allows to identify patients with high residual plasma hypercoagulability.

PMID- 24094603
TI  - The predictive value of heart-type fatty acid-binding protein is independent from
      symptom duration in normotensive patients with pulmonary embolism.
AB  - BACKGROUND: Heart-type fatty acid-binding protein (H-FABP) is a useful biomarker
      for risk stratification of patients with pulmonary embolism (PE). In patients
      with acute myocardial infarction, H-FABP plasma concentrations rise after 30
      minutes and return to normal within 20-24 hours. We tested whether the predictive
      value of H-FABP is affected by the duration of symptoms prior to diagnosis in
      patients with PE. MATERIAL AND METHODS: We prospectively studied 257 consecutive
      normotensive patients with confirmed symptomatic PE. RESULTS: Patients with acute
      (<24 hours; n=150) symptom onset presented more often with syncope (28.7% vs.
      6.5%; p<0.001) compared to patients with symptoms >= 24 hours (n=107); other
      baseline characteristics, comorbidities, and risk factors were distributed
      equally. Patients with an adverse 30-day outcome (6.6%) had higher H-FABP levels
      (11.84 [3.57-19.62] ng/ml) compared to patients with a favorable course (3.42
      [1.92-5.42] ng/ml; p<0.001). However, the proportion of patients with H-FABP
      levels >= 6 ng/ml did not differ among patients with acute symptom onset and late
      presentation (p=0.104). Only tachycardia and elevation of H-FABP were associated
      with an increased risk of an adverse 30-day outcome both in patients with acute
      symptom onset (H-FABP: OR, 5.8; 95% CI, 1.4-24.5; p=0.016; tachycardia: 7.0 [1.4
      36.0]; p=0.018) and late presentation (H-FABP: 9.3 [2.0-43.2]; p=0.004 and
      tachycardia: 12.3 [1.5-103.6]; p=0.021). The prognostic value could further be
      improved by the use of a simple H-FABP-based clinical prediction score.
      CONCLUSIONS: Our findings indicate that H-FABP is a useful biomarker for risk
      stratification of normotensive patients with PE regardless of symptom duration
      prior to diagnosis.

PMID- 24094604
TI  - Flow cytometry demonstrates differences in platelet reactivity and microparticle
      formation in subjects with thrombocytopenia or thrombocytosis due to primary
      haematological disorders.
AB  - BACKGROUND: Traditional methods for the assessment of platelet function require a
      minimum number of platelets. As flow cytometry is independent of platelet number,
      we measured platelet activation and microparticle formation in thrombocytopenia
      and thrombocytosis. MATERIALS AND METHODS: Blood was obtained from normal
      subjects or subjects with immune thrombocytopenic purpura (ITP), myelodysplasia
      (MDS) or essential thrombocythaemia (ET). Platelet activation and microparticle
      formation were assessed in resting and agonist stimulated samples. RESULTS:
      Platelet activation was significantly decreased in MDS in agonist-stimulated
      platelets when compared to normals and ITP, however increased microparticle-to
      platelet ratios were found. Absolute platelet-derived microparticle counts were
      significantly higher in ET when compared to normals, but there was no significant
      difference in microparticle-to-platelet ratios between ET and normals.
      CONCLUSIONS: Decreased platelet activation was demonstrated in MDS when compared
      to normal subjects and ITP. Platelet-derived microparticle counts are increased
      in ET, reflecting increased platelet counts rather than an increase in platelet
      reactivity. Flow cytometric analysis of platelets may aid the diagnosis and
      management of these conditions.

PMID- 24094606
TI  - Oral intradialytic nutritional supplement use and mortality in hemodialysis
      patients.
AB  - BACKGROUND: Hemodialysis patients have high mortality rates, potentially
      reflecting underlying comorbid conditions and ongoing catabolism. Intradialytic
      oral nutritional supplements may reduce this risk. STUDY DESIGN: Retrospective
      propensity-matched cohort. SETTING & PARTICIPANTS: Maintenance hemodialysis
      patients treated at Dialysis Clinic Inc facilities who were initiated on a
      nutritional supplement protocol in September to October 2010 were matched using a
      propensity score to patients at facilities at which the protocol was not used.
      PREDICTORS: Prescription of the protocol, whereby hemodialysis patients with
      serum albumin levels <=3.5g/dL would initiate oral protein supplementation during
      the dialysis procedure. Sensitivity analyses matched on actual supplement intake
      during the first 3 study months. Covariates included patient and facility
      characteristics, which were used to develop the propensity scores and adjust
      multivariable models. OUTCOMES: All-cause mortality, ascertained though March
      2012. RESULTS: Of 6,453 eligible patients in 101 eligible hemodialysis
      facilities, the protocol was prescribed to 2,700, and 1,278 of these were
      propensity matched to controls. Mean age was 61 +/- 15 (SD) years and median
      dialysis vintage was 34 months. There were 258 deaths among protocol assignees
      versus 310 among matched controls during a mean follow-up of 14 months. In
      matched analyses, protocol prescription was associated with a 29% reduction in
      the hazard of all-cause mortality (HR, 0.71; 95% CI, 0.58-0.86); adjustment had
      minimal impact on models. In time-dependent models incorporating change in
      albumin level, protocol status remained significant but was attenuated in models
      incorporating a 30-day lag. Similar results were seen in sensitivity analyses of
      439 patients receiving supplements who were propensity-matched to controls, with
      116 deaths among supplement users versus 140 among controls (HR, 0.79; 95% CI,
      0.60-1.05), achieving statistical significance in adjusted models. LIMITATIONS:
      Observational design, potential residual confounding. CONCLUSIONS: Prescription
      of an oral nutritional supplement protocol and use of oral protein nutritional
      supplements during hemodialysis are associated with reduced mortality among in
      center maintenance hemodialysis patients, an effect likely not mediated by change
      in serum albumin levels.

PMID- 24094605
TI  - Ambivalent roles of carboxypeptidase B in the lytic susceptibility of fibrin.
AB  - BACKGROUND: Removal of C-terminal lysine residues that are continuously exposed
      in lysing fibrin is an established anti-fibrinolytic mechanism dependent on the
      plasma carboxypeptidase TAFIa, which also removes arginines that are exposed at
      the time of fibrinogen clotting by thrombin. OBJECTIVE: To evaluate the impact of
      alterations in fibrin structure mediated by constitutive carboxypeptidase
      activity on the function of fibrin as a template for tissue plasminogen activator
      (tPA) induced plasminogen activation and its susceptibility to digestion by
      plasmin. METHODS AND RESULTS: We used the stable carboxypeptidase B (CPB), which
      shows the same substrate specificity as TAFIa. If 1.5 - 6MUM fibrinogen was
      clotted in the presence of 8U/mL CPB, a denser fibrin network was formed with
      thinner fibers (the median fiber diameter decreased from 138 - 144nm to 89 -
      109nm as established with scanning electron microscopy). If clotting was
      initiated in the presence of 5 - 10MUM arginine, a similar decrease in fiber
      diameter (82 -95nm) was measured. The fine structure of arginine-treated fibrin
      enhanced plasminogen activation by tPA, but slowed down lysis monitored using
      fluorescent tPA and confocal laser microscopy. However, if lysis was initiated
      with plasmin in CPB-treated fibrin, the rate of dissolution increased to a degree
      corresponding to doubling of the plasmin concentration. CONCLUSION: The present
      data evidence that CPB activity generates fine-mesh fibrin which is more
      difficult to lyse by tPA, but conversely, CPB and plasmin together can stimulate
      fibrinolysis, possibly by enhancing plasmin diffusion.

PMID- 24094607
TI  - The association between self-reported change in vote for the presidential
      election of 2012 and posttraumatic stress disorder symptoms following Hurricane
      Sandy.
AB  - The relationship between vote change for the presidential election in 2012 and
      posttraumatic stress disorder (PTSD) symptoms has not been previously explored.
      An online sample of 1000 people mainly from New York Metropolitan Area was
      surveyed during the fourth week of November 2012 after Hurricane Sandy, shortly
      after the US Presidential election. Participants completed a questionnaire
      battery which included disaster related questions and PTSD symptoms. Logistic
      regression revealed a significant association between vote change and elevated
      risk for PTSD symptoms. This result may indicate that PTSD symptoms are
      associated with behavioral actions such as vote change. 

PMID- 24094608
TI  - Scale for the Assessment of Negative Symptoms structure in first episode
      psychosis.
AB  - Previous studies in schizophrenia samples suggest negative symptoms can be
      categorized as expressivity or experiential. This study examines the structure of
      the Scale for the Assessment of Negative Symptoms (SANS) at two separate
      interviews in a first episode psychosis (FEP) sample. SANS structure was
      determined with principal components analysis in a schizophrenia spectrum (SSD,
      N=191) and non-schizophrenia spectrum (NSSD, N=246) sample at first presentation.
      Confirmatory factor analysis (CFA) was conducted in the entire FEP sample (N=197)
      at a follow-up assessment. A three factor model solution was extracted in both
      SSD and NSSD at first presentation. The three components, consisting of
      expressivity, experiential and alogia/inattention components, explained 26.1%,
      16.6% and 13.6% of the variance respectively in SSD. In NSSD the same three
      components explained 24.2%, 17.9% and 13.1% of the variance respectively. CFA at
      follow-up showed similar model fit for both the original SANS five factor and for
      a three factor model solution. The results indicate that either a three or five
      factor SANS model solution may be appropriate in a psychosis sample inclusive of
      both SSD and NSSD. The findings also provide initial support for expressivity and
      experiential domain research in NSSD. 

PMID- 24094609
TI  - Neck/shoulder and back pain in new graduate nurses: A growth mixture modeling
      analysis.
AB  - BACKGROUND: Although it is well known that musculoskeletal disorders are common
      among registered nurses, little longitudinal research has been conducted to
      examine this problem from nursing education to working life. OBJECTIVES: The aim
      was to investigate the prevalence and incidence of neck/shoulder and back pain in
      nursing students in their final semester, and one and two years after graduation.
      Furthermore, to identify common trajectories of neck/shoulder and back pain, and
      explore sociodemographic and lifestyle-related factors, contextual factors and
      health outcome that might be characteristic of individuals in the various
      trajectories. DESIGN: Longitudinal study following nursing students from their
      final year of studies, with follow-ups one and two years after graduation.
      SETTINGS AND PARTICIPANTS: Nursing students who graduated from the 26
      universities providing undergraduate nursing education in Sweden 2002 were
      invited to participate (N=1700). Of those asked, 1153 gave their informed
      consent. METHODS: The participants answered postal surveys at yearly intervals.
      Descriptive statistics were used to analyze prevalence and incidence of pain, and
      growth mixture modeling was applied to identify different homogeneous clusters of
      individuals following similar trajectories in pain development across time.
      RESULTS: The prevalence of neck/shoulder and back pain remained constant over
      time (around 50% for neck/shoulder pain and just over 40% for back pain). Six
      different development trajectories for each symptom were found, reflecting
      patterns of stable pain levels or variation in levels over time: one symptom-free
      group, two decreasing pain groups, two increasing pain groups, and one chronic
      pain group. With few exceptions, the same factors (sex, children, chronic
      disease, working overtime, work absence, sickness presence, physical load,
      depression, self-rated health, sleep quality and muscular tension) were
      associated with neck/shoulder and back pain trajectories. Different types of
      physical load characterized new nurses with neck/shoulder pain and back pain
      respectively. CONCLUSIONS: The high prevalence of pain among nursing students and
      among new graduate nurses, suggests that it would be effective to implement
      preventive strategies already during nursing education, but they should also
      preferably continue after graduation. Many factors associated with pain in the
      neck/shoulder and back seem to be modifiable, and thereby constitute targets for
      preventive strategies.

PMID- 24094610
TI  - Changes in and predictors of severity of fatigue in women with breast cancer: A
      longitudinal study.
AB  - BACKGROUND: Fatigue is the most common symptom experienced by cancer patients.
      However, longitudinal studies of changes in the severity and predictors of
      fatigue are limited. OBJECTIVES: The purposes of this study were to evaluate
      changes in fatigue severity in women with breast cancer prior to and for twelve
      months after surgery. Factors that affected the severity and the trajectory of
      fatigue were identified. DESIGN, SETTINGS, PARTICIPANTS: This observational
      prospective study approached 334 women who were scheduled for breast cancer
      surgery in a medical center located in northern Taiwan. Among the 334 women, 239
      met the inclusion/exclusion criteria. The final sample size used for the data
      analysis was 200. METHODS: Fatigue, depressive symptom, and symptom distress were
      evaluated in women prior to and at 1, 2, 3, 4, 5, 6, 8, 10, and 12 months after
      surgery for breast cancer. Hierarchical linear modeling (HLM) was applied where
      level-1 data consisted of repeated observations of study variables within each
      subject and level-2 data consisted of static characteristics of individual
      subject. RESULTS: The fatigue levels ranged from 1.92 to 3.09. Changes in fatigue
      severity demonstrated a quadratic trajectory that increased and reached the peak
      at the second month after the surgery, followed by a gradual decreased. After
      adjusting for the effect of receipt of chemotherapy, symptom distress, and
      depressive symptom, the quadratic change pattern for fatigue became
      imperceptible. Women who had a partial mastectomy (P=0.028), had a higher
      educational level (P=0.048), were married (P=0.043), and had poorer functional
      performance at diagnosis (P=0.043) had higher levels of fatigue. CONCLUSIONS:
      Patients who underwent surgery for breast cancer reported mild to moderate levels
      of fatigue over a period of 12 months. Fatigue levels fluctuated with patients'
      level of depressive symptoms, symptom distress, and receipt of chemotherapy.

PMID- 24094611
TI  - Correlations between ankle-foot impairments and dropped foot gait deviations
      among stroke survivors.
AB  - BACKGROUND: The purpose of this paper is to 1) evaluate the relationship between
      ankle kinematics during gait and standardized measures of ankle impairments among
      sub-acute stroke survivors, and 2) compare the degree of stroke-related ankle
      impairment between individuals with and without dropped foot gait deviations.
      METHODS: Fifty-five independently ambulating stroke survivors participated in
      this study. Dropped foot was defined as decreased peak dorsiflexion during the
      swing phase and reduced ankle joint motion in stance. Standardized outcome
      measures included the Chedoke-McMaster Stroke Assessment (motor impairment),
      Modified Ashworth Scale (spasticity), Medical Research Council (muscle strength),
      passive and active range of motion, and isometric muscle force. FINDINGS: Foot
      impairment was not related to peak dorsiflexion during swing (r=-0.17, P=0.247)
      and joint motion during stance (r=0.05, P=0.735). Active (r=0.45, P<0.001) and
      passive (r=0.48, P<0.001) range of motion was associated with stance phase joint
      motion. Peak dorsiflexion during swing was related to isometric dorsiflexor
      muscle force (r=-0.32, P=0.039). Individuals with dropped foot demonstrated
      greater motor impairment, plantarflexor spasticity and ankle muscle weakness
      compared to those without dropped foot. INTERPRETATION: Our investigation
      suggests that ankle-foot impairments are related to ankle deviations during gait,
      as indicated by greater impairment among individuals with dropped foot. These
      findings contribute to a better understanding of gait-specific ankle deviations,
      and may lead to the development of a more effective clinical assessment of
      dropped foot impairment.

PMID- 24094612
TI  - ST-elevation/non-ST-elevation acute myocardial infarctions, infarct size, and
      transmurality: somewhat unfair comparisons.

PMID- 24094613
TI  - The cost-effectiveness of depression treatment for co-occurring disorders: a
      clinical trial.
AB  - The authors aimed to determine the economic value of providing on-site group
      cognitive behavioral therapy (CBT) for depression to clients receiving
      residential substance use disorder (SUD) treatment. Using a quasi-experimental
      design and an intention-to-treat analysis, the incremental cost-effectiveness and
      cost-utility ratio of the intervention were estimated relative to usual care
      residential treatment. The average cost of a treatment episode was $908, compared
      to $180 for usual care. The incremental cost effectiveness ratio was $131 for
      each point improvement of the BDI-II and $49 for each additional depression-free
      day. The incremental cost-utility ratio ranged from $9,249 to $17,834 for each
      additional quality adjusted life year. Although the intervention costs
      substantially more than usual care, the cost effectiveness and cost-utility
      ratios compare favorably to other depression interventions. Health care reform
      should promote dissemination of group CBT to individuals with depression in
      residential SUD treatment. 

PMID- 24094614
TI  - Extraoral implants for orbit rehabilitation: a comparison between one-stage and
      two-stage surgeries.
AB  - The aim of the study was to compare the osseointegration success rate and time
      for delivery of the prosthesis among cases treated by two-stage or one-stage
      surgery for orbit rehabilitation between 2003 and 2011. Forty-five patients were
      included, 31 males and 14 females; 22 patients had two-stage surgery and 23
      patients had one-stage surgery. A total 138 implants were installed, 42 (30.4%)
      on previously irradiated bone. The implant survival rate was 96.4%, with a
      success rate of 99.0% among non-irradiated patients and 90.5% among irradiated
      patients. Two-stage patients received 74 implants with a survival rate of 94.6%
      (four implants lost); one-stage surgery patients received 64 implants with a
      survival rate of 98.4% (one implant lost). The median time interval between
      implant fixation and delivery of the prosthesis for the two-stage group was 9.6
      months and for the one-stage group was 4.0 months (P < 0.001). The one-stage
      technique proved to be reliable and was associated with few risks and
      complications; the rate of successful osseointegration was similar to those
      reported in the literature. The one-stage technique should be considered a viable
      procedure that shortens the time to final rehabilitation and facilitates
      appropriate patient follow-up treatment.

PMID- 24094615
TI  - In vitro resistance of titanium and resorbable (poly L-co-DL lactic acid)
      osteosynthesis in mandibular body fracture.
AB  - This study was a comparative evaluation of the bending resistance of metallic and
      resorbable plates and screws in a mandibular body fracture model. Forty
      polyurethane synthetic hemimandibles were used; a vertical linear cut was made
      between the second and first premolars. These 40 hemimandibles were divided into
      four groups of 10 and were fixed with titanium plates and screws or resorbable
      plates and screws, with monocortical screws in the upper sector and bicortical
      screws in the lower sector. Bending resistance tests were done on a universal
      testing machine with a linear displacement speed of 1mm/min, a cell load of 500
      N, and a load cell on the lower central incisor or on the lower second premolar.
      Results were analyzed using the Student's t-test, with the significance level set
      at 5%. No statistically significant differences were observed between the groups
      studied, either in the analysis of the osteosynthesis materials or related to the
      load-bearing points. The variables of displacement and peak load did not present
      any significant differences. In this in vitro model of a mandibular body
      fracture, the mechanical behaviour of a resorbable osteosynthesis was similar to
      that of a titanium osteosynthesis.

PMID- 24094616
TI  - Re: 'recovery of two-point discrimination function after digital nerve repair in
      the hand using resorbable FDA- and CE-approved nerve conduits' by M.F. Meek and
      J.H. Coert. J Plast Reconstr Aesthet Surg. 2013 Oct;66(10):1307-15.

PMID- 24094617
TI  - Power assisted liposuction to obtain adipose-derived stem cells: impact on
      viability and differentiation to adipocytes in comparison to manual aspiration.
AB  - BACKGROUND: Adipose-derived stem cells (ASCs) play a key role in tissue
      engineering approaches and are probably of major importance in the context of
      autologous fat transfer. A number of different tools for harvesting ASCs
      containing fat tissue have been established. Such devices should be easy to
      handle, time saving, low priced, safe and provide a high amount of viable ASCs in
      the aspirate. Power-assisted liposuction (PAL) has not yet been described in the
      literature as a tool for fat harvesting for lipotransfer. Aim of this study was
      to investigate ASCs' viability in fat tissue harvested using PAL versus manual
      aspiration (MA). METHODS: Fat tissue was obtained from 9 donors undergoing
      abdominoplasty. Samples were divided into two sections. Out of each section fat
      was harvested using either PAL or MA. Number of isolated ASCs was defined,
      proliferation rate was determined and cell viability was assessed by flow
      cytometry. The ability of isolated ASCs to differentiate into mature adipocytes
      was analyzed by gene marker expression. RESULTS: The number of viable ASCs and
      the proliferation rates did not significantly differ between PAL and MA but cells
      harvested using PAL showed significantly higher expression levels of
      differentiation markers adiponectin, GLUT4 and PPARg. CONCLUSION: Our results
      show that PAL is a feasible method for harvesting fat tissue containing viable
      ASCs. Quantity and quality of PAL-harvested ASC is similar or even better,
      respectively, compared to ASCs harvested by MA.

PMID- 24094618
TI  - Management of flap venous congestion: the role of heparin local subcutaneous
      injection.
AB  - OBJECTIVE: The study aimed to propose an alternative salvage technique based on
      local subcutaneous injection of low molecular-weight heparin (LMWH) for the
      management of venous congested pedicle and free flaps in which venous outflow
      could not be surgically restored. METHODS: A retrospective review of all patients
      who received the proposed protocol at a single centre was performed. RESULTS:
      Fifteen patients were treated (six free flaps and nine regional flaps). The LMWH
      protocol was applied for a mean of 11 days (10-14 days). Thirteen patients
      required transfusions with a mean number of 5 U (0-12 U) of packed red blood
      cells (PRBCs) transfused per patient. All flaps were successfully salvaged (seven
      totally and eight partially). There were two associated complications: one
      patient developed a recipient-site haematoma and another patient suffered a
      syncope episode, related to anaemia. CONCLUSIONS: Local subcutaneous injection of
      LMWH was proven to be an effective alternative in improving flap venous
      congestion. The main advantages of this procedure are availability, easy
      application and local limited action. However, the associated morbidity should be
      balanced against the risk of flap loss and a judicious application is mandatory.

PMID- 24094619
TI  - A systematic review of the use of Botulinum toxin type A with subpectoral breast
      implants.
AB  - OBJECTIVE: To determine the efficacy of Botulinum toxin A (BTX-A) injections for
      pain relief following placement of subpectoral tissue expanders and breast
      implants. METHODS: MEDLINE and EMBASE were searched from their inception to
      December 2012 to identify studies reporting the efficacy of perioperative BTX-A
      injections following breast surgery with subpectoral prostheses. Study designs
      included controlled and uncontrolled studies. RESULTS: Seven studies met the
      inclusion criteria (2 prospective controlled cohort, 3 retrospective cohort and 2
      case series). Five studies assessed the efficacy of BTX-A and three measured pain
      improvement as a primary outcome. The studies enrolled 427 women: 91.8% received
      intraoperative BTX-A injection at the time of tissue expander breast
      reconstruction and 4.7% following augmentation mammaplasty. Only 3.5% of women
      received BTX-A injections in the postoperative setting. Overall, all the studies
      demonstrated improvement in pain and favorable side effect profile without any
      major adverse effects. However, the quality of this evidence was low. CONCLUSION:
      The results of this systematic review suggest that BTX-A may alleviate
      postoperative pain associated with the placement of subpectoral tissue expanders
      and implants. The available data on outcome assessment of this practice are
      inconsistent and lack methodological rigor. With paucity of high-level evidence
      to support this practice in implant-based breast surgery, further studies are
      needed.

PMID- 24094620
TI  - Agenesis of the gallbladder: a case report.

PMID- 24094621
TI  - [Levofloxacin-induced autoimmune hepatitis. Description of a case].

PMID- 24094622
TI  - [Outcome of chronic hepatitis B and C in patients with inflammatory bowel disease
      treated with immunosuppressive drugs and anti-TNF agents].

PMID- 24094623
TI  - [Spontaneous small bowel evisceration through the vagina].

PMID- 24094624
TI  - Ulcerated Meckel's diverticulum.

PMID- 24094625
TI  - Flavonoids as drugs at the small intestinal level.
AB  - Flavonoids represent a biologically active class of secondary plant compounds.
      For selected members there is convincing evidence regarding their beneficial
      effects on human health. Accordingly these compounds are tested as supporting or
      alternative therapies for a number of diseases such as cancer or type-II
      diabetes. Subsequent to their ingestion a first site of interference are
      digestive enzymes and transporters in the small intestine. Through interactions
      with glucose transporters in the apical membranes of enterocytes flavonoid
      glycosides and also some aglycones appear to reduce postprandial hyperglycaemia
      in diabetic patients. Moreover, many flavonoids have been shown to interfere with
      ATP-dependent drug-efflux transporters which are relevant for the resistance of
      cancer cells versus various cytostatic drugs and makes them candidates to
      overcome multidrug-resistance. 

PMID- 24094626
TI  - Accelerated hypo-fractionated radiotherapy for non small cell lung cancer:
      results from 4 UK centres.
AB  - BACKGROUND AND PURPOSE: A variety of radiotherapy fractionations are used as
      potentially curative treatments for non-small cell lung cancer. In the UK, 55 Gy
      in 20 fractions over 4 weeks (55/20) is the most commonly used fractionation
      schedule, though it has not been validated in randomized phase III trials. This
      audit pooled together existing data from 4 UK centres to produce the largest
      published series for this schedule. MATERIALS AND METHODS: 4 UK centres
      contributed data (Cambridge, Cardiff, Glasgow and Sheffield). Case notes and
      radiotherapy records of radically treated patients between 1999 and 2007 were
      retrospectively reviewed. Basic patient demographics, tumour characteristics,
      radiotherapy and survival data were collected and analysed. RESULTS: 609 patients
      were identified of whom 98% received the prescribed dose of 55/20. The median age
      was 71.3 years, 62% were male. 90% had histologically confirmed NSCLC, 49% had
      stage I disease. 27% had received chemotherapy (concurrent or sequential) with
      their radiotherapy. The median overall survival from time of diagnosis was 24.0
      months and 2 year overall survival was 50%. CONCLUSION: These data show
      respectable results for patients treated with accelerated hypo-fractionated
      radiotherapy for NSCLC with outcomes comparable to those reported for similar
      schedules and represent the largest published series to date for 55/20 regime.

PMID- 24094627
TI  - Reduction in cardiac volume during chemoradiotherapy for patients with esophageal
      cancer.
AB  - We investigated the change in cardiac volume over the course of chemoradiotherapy
      in 26 patients treated for esophageal cancer, using cone beam CT imaging. The
      cardiac volume reduced significantly, with a median reduction of 8%. A
      significant relationship with planned cardiac dose was not found. 

PMID- 24094628
TI  - Simulation of realistic linac motion improves the accuracy of a Monte Carlo based
      VMAT plan QA system.
AB  - PURPOSE: To investigate the use of a software-based pre-treatment QA system for
      VMAT, which incorporates realistic linac motion during delivery. METHODS: A beam
      model was produced using the GATE platform for GEANT4 Monte Carlo dose
      calculations. Initially validated against static measurements, the model was then
      integrated with a VMAT delivery emulator, which reads plan files and generates a
      set of dynamic delivery instructions analogous to the linac control system. Monte
      Carlo simulations were compared to measurements on dosimetric phantoms for
      prostate and head and neck VMAT plans. Comparisons were made between calculations
      using fixed control points, and simulations of continuous motion utilising the
      emulator. For routine use, the model was incorporated into an automated pre
      treatment QA system. RESULTS: The model showed better agreement with measurements
      when incorporating linac motion: mean gamma pass (Gamma<1) over 5 prostate plans
      was 100.0% at 3%/3mm and 97.4% at 2%/2mm when compared to measurement. For the
      head and neck plans, delivered to the anatomical phantom, gamma passes were 99.4%
      at 4%/4mm and 94.94% at 3%/3mm. For example simulations within patient CT data,
      gamma passes were observed which are within our centre's tolerance for pre
      treatment QA. CONCLUSIONS: Through comparison to phantom measurements, it was
      found that the incorporation of a realistic linac motion improves the accuracy of
      the model compared to the simulation of fixed control points. The ability to
      accurately calculate dose as a second check of the planning system, and determine
      realistic delivery characteristics, may allow for the reduction of machine-based
      pre-treatment plan QA for VMAT.

PMID- 24094629
TI  - Independent prospective validation of a predictive test for risk of radiation
      induced fibrosis based on the gene expression pattern in fibroblasts irradiated
      in vitro.
AB  - PURPOSE: In a previously published study, we established a predictive test for
      the risk of radiation-induced fibrosis based on the gene expression pattern in
      cultured fibroblast irradiated in vitro. The present study was conducted to seek
      an independent prospective validation of the predictive test in a cohort of
      patients given curative radiotherapy for head and neck cancer. MATERIALS AND
      METHODS: The study cohort comprised 160 consecutive head and neck cancer patients
      given curative radiotherapy between 2000 and 2004. The patients were treated
      according to the DAHANCA protocols. The patients were scored for subcutaneous
      fibrosis as part of routine follow up. Fibroblast culture was established from
      skin biopsies. The fibroblasts were irradiated in vitro using a fractionation
      scheme of 3 times 3.5 Gy. The expression of 9 genes was assessed before and after
      irradiation of the cells using real time PCR. RESULTS: Based on the radiation
      induced expression of the assessed genes, the material was divided into 136
      patients having the 'sensitive expression profile' and 24 patients having the
      'resistant expression profile'. Within the subset of patients with the 'sensitive
      profile', the cumulative risk of severe fibrosis was 34% at 9 years (Kaplan
      Meier) whereas no patients with the 'resistant profile' developed severe fibrosis
      (p = 0.035). CONCLUSION: Our study provided an independent prospective validation
      of the previously established predictive test for radiation induced fibrosis. In
      agreement with our initial findings, the classifier was able to identify a
      smaller subset of patients that seems to be rather radioresistant and could
      therefore potentially be considered for dose escalation.

PMID- 24094630
TI  - Re-irradiation for painful bone metastases - a systematic review.
AB  - The purpose of this review was to determine the efficacy of re-irradiation in
      patients with bone metastases. A literature search was conducted in Ovid Medline,
      OldMedline, Embase, Embase Classic, and Cochrane Central Register of Controlled
      Trials using relevant subject headings and keywords such as bone metastases,
      radiotherapy and palliative care. The resulting articles were sorted for
      inclusion for palliative external beam radiation retreatment response rate data.
      The literature search produced 2164 references and 15 articles were included in
      the final selection. Complete, partial and overall response rates were calculated
      to be 20%, 50% and 68%, respectively. Information on treatment toxicities was
      scarce. The efficacy of re-irradiation is comparable to initial radiation
      treatment. However, aspects of re-irradiation treatment including dose
      fractionation, related adverse events and toxicities require further
      corroboration. 

PMID- 24094631
TI  - Registration accuracy and image quality of time averaged mid-position CT scans
      for liver SBRT.
AB  - PURPOSE AND BACKGROUND: The purpose was to validate the accuracy of motion models
      derived from deformable registration from four-dimensional computed tomography
      (4DCT) and breath-hold contrast enhanced computed tomography (BHCCT) scans for
      liver SBRT. Additionally, the image quality of the time averaged mid-position
      (MidP) CT constructed using the detected motion model was assessed. MATERIALS AND
      METHODS: 4DCT and BHCCT liver scans of 11 patients were acquired with 1 or 2
      fiducial markers. Using parametric sampling the markers were digitally removed.
      Phase-based optical flow was used to register the 4D frames and the BHCCT, and
      create MidP data. We compared the deformable registration of the markerless scans
      with the actual displacement of the markers to assess registration accuracy. The
      noise levels of the MidP scans were compared to those of the 4DCT and BHCCT data.
      RESULTS: We found an average misregistration of 1.8mm (+/- 0.5mm). The
      constructed MidPCT scan contained around three times less noise than the original
      4D scan. The residual error between the MidPCT and the BHCCT was 3.0mm (+/- 0.9
      mm). CONCLUSIONS: High precision deformable image registration of 4DCT and BHCCT
      liver cancer patients was achieved and used to create motion compensated MidPCT
      scans, with increased contrast-to-noise (CNR) levels. This improved visualisation
      of tumours and anatomy, facilitates radiotherapy treatment planning.

PMID- 24094632
TI  - Motion compensated digital tomosynthesis.
AB  - BACKGROUND AND PURPOSE: Digital tomosynthesis (DTS) is a limited angle image
      reconstruction method for cone beam projections that offers patient surveillance
      capabilities during VMAT based SBRT delivery. Motion compensation (MC) has the
      potential to mitigate motion artifacts caused by respiratory motion, such as
      blur. The purpose of this feasibility study was therefore to develop and evaluate
      motion-compensated DTS (MC-DTS). MATERIAL AND METHODS: MC-DTS images were
      reconstructed by back projection of X-ray projection images acquired over 30
      degrees  arcs. Back projection lines were deformed according to an a priori
      motion model derived from the 4D planning CT. MC-DTS was evaluated on a
      respiratory motion phantom and 3 lung cancer patients. Respiratory artifact
      reduction was assessed visually and quantified by fitting a cumulative Gaussian
      function to profiles along the background-GTV transition in the CC direction.
      RESULTS: MC reconstruction was fast enough to keep up with image acquisition and
      considerably reduced motion blur visually. Quantitatively, MC reduced the
      background-GTV transition distance by 49%. CONCLUSION: Motion compensation
      considerably improved the image quality of DTS images of lung cancer patients,
      giving an opportunity for more accurate DTS guidance and intra-fraction
      monitoring concurrent with VMAT delivery.

PMID- 24094633
TI  - The role of myelin and oligodendrocytes in axonal energy metabolism.
AB  - In vertebrates, the myelination of long axons by oligodendrocytes and Schwann
      cells enables rapid impulse propagation. However, myelin sheaths are not only
      passive insulators. Oligodendrocytes are also known to support axonal functions
      and long-term integrity. Some of the underlying mechanisms have now been
      identified. It could be shown that oligodendrocytes can survive in vivo by
      aerobic glycolysis. Myelinating oligodendrocytes release lactate through the
      monocarboxylate transporter MCT1. Lactate is then utilized by axons for
      mitochondrial ATP generation. Studying axo-glial signalling and energy metabolism
      will lead to a better understanding of neurodegenerative diseases, in which
      axonal energy metabolism fails. These include neurological disorders as diverse
      as multiple sclerosis, leukodystrophies, and amyotrophic lateral sclerosis. 

PMID- 24094634
TI  - Pitfalls in hormone determinations.

PMID- 24094635
TI  - Principles and pitfalls of free hormone measurements.
AB  - The free hormone hypothesis states that a hormone's physiological effects depend
      on the free hormone concentration, not the total hormone concentration. Although
      the in vivo relationship between free hormone and protein-bound hormone is
      complex, most experts have applied this view to the design of assays used to
      assess the free hormone concentration in the blood sampled for testing in vitro.
      The history of the measurement of free thyroxine, probably the most frequently
      requested free hormone determination, offers a good example of the approaches
      that have been taken. Methods that require physical separation of the free
      hormone from the protein-bound hormone must address both the potential
      disturbance in the equilibrium between the two, as well as the challenge of
      quantifying small levels of hormone accurately and precisely. The implementation
      of mass spectrometry in the clinical laboratory has helped to develop proposed
      reference measurement procedures. These must be utilized to standardize the
      variety of immunoassay approaches that currently represent options commercially
      available to the routine clinical laboratory. Practicing endocrinologists should
      discuss the details of the free hormone assays offered by the clinical laboratory
      they utilize for patient result reporting, and clinical laboratories should
      implement the recommendations of published guidelines to ensure that free hormone
      results using commercially available immunoassays are as accurate and precise as
      possible. 

PMID- 24094636
TI  - Heterophilic antibody interference in immunometric assays.
AB  - Immunometric assays are inherently vulnerable to interference from heterophilic
      antibodies, endogenous antibodies that bind assay antibodies. The consequences of
      such interference can be devastating. In this review, we discuss strategies that
      reduce the damage caused by heterophilic antibodies. Clinicians should only order
      blood tests that are indicated for the patient and clinical setting at hand, and
      have the confidence to question laboratory results discordant with the clinical
      picture. Laboratorians should familiarize themselves with the vulnerability of
      the assays they offer, and be able to perform and interpret adequate confirmatory
      measures correctly. When designing immunoassays, the immunoassay industry should
      invest the necessary resources in specific protective measures against
      heterophilic antibody interference. Examples include using antibody fragments and
      the addition of effective blockers to assay reagents. The increasing use of
      modified monoclonal mouse antibodies both in therapy and diagnostics could
      present a particular challenge in the future. 

PMID- 24094637
TI  - Novel liquid chromatography tandem mass spectrometry (LC-MS/MS) methods for
      measuring steroids.
AB  - Liquid chromatography tandem mass spectrometry (LC-MS/MS) is increasingly
      becoming the method of choice for steroid hormone measurements due to small
      sample volumes, fast analysis times and improved specificity compared to
      immunoassays. Achievement of demanding analytical targets for steroid analysis is
      now becoming possible because of improvements in sample preparation technology,
      liquid chromatography column technology and mass spectrometer design. The most
      popular sample treatment strategies comprise protein precipitation (PP), solid
      phase extraction (SLE) and liquid-liquid extraction (LLE). Modern liquid
      chromatography columns can ensure the adequate separation of isobaric compounds
      e.g. 21 Deoxycortisol, 11 Deoxycortisol and Corticosterone. The most appropriate
      method may be chosen to improve assay sensitivity by reducing matrix effects
      (LLE, SPE) or simplicity and speed (PP). Specific examples of some clinically
      important steroids including oestradiol, aldosterone, renin, serum cortisol,
      salivary cortisol and salivary testosterone will be described. 

PMID- 24094638
TI  - Determination of vitamin D and its metabolites.
AB  - The demand for analysis of 25-hydroxyvitamin D has increased dramatically
      throughout the world over the past decade. As a consequence, a number of new
      automated assays have been introduced for 25-hydroxyvitamin D measurement.
      Automated assays have shown variable ability to meet the technical challenges
      associated with 25-hydroxyvitamin D measurement. Assays are able to meet
      performance goals for precision at high concentrations but fail to do so at low
      concentrations of 25-hydroxyvitamin D. The overall accuracy of automated methods
      has improved over recent years and generally shows good overall agreement with
      reference methods; however, discrepancies persist for individual samples. Liquid
      chromatography-tandem mass spectrometry is used by some routine laboratories for
      25-hydroxyvitamin D analysis but its widespread use is hampered by limited sample
      throughput. 1,25-Dihydroxyvitamin D is an important analyte in specific clinical
      situations, which remains in the hands of specialised laboratories using manual
      analytical methods. 

PMID- 24094639
TI  - Determination of free thyroid hormones.
AB  - Timely diagnosis and treatment of thyroid dysfunction is compelling given the
      prevalence and severity of the disease. It requires reliance on adequate
      laboratory testing of serum TSH as a hallmark in combination with free
      thyroxine/triiodothyronine. Free hormone methods have to accommodate variations
      in the concentration and binding capacity of binding proteins. This is a
      challenge because none of the methodologies developed so far measures the actual
      unbound hormone in serum. The indirect methods provide an approximation while the
      direct ones estimate the free hormone concentration either in the presence of the
      protein-bound counterpart, or after physical separation of the free from bound
      fraction. The ongoing controversy on the validity and lack of comparability of
      methodologies points to their imperfectness to reflect real in-vivo free hormone
      concentrations. Therefore, laboratories and clinicians should know the window of
      validity and limitations of their methods. The recently developed reference
      measurement system is a key advance towards improved standardization and clinical
      validity of free thyroid hormone measurements. 

PMID- 24094640
TI  - Thyroglobulin antibody (TgAb) methods - Strengths, pitfalls and clinical utility
      for monitoring TgAb-positive patients with differentiated thyroid cancer.
AB  - Thyroglobulin autoantibodies (TgAb) are detected at diagnosis or during treatment
      in approximately 25% of patients with differentiated thyroid cancer (DTC). When
      present, TgAb interferes with thyroglobulin (Tg) measurement causing falsely low
      or undetectable Tg immunometric assay (IMA) values that can mask disease.
      Guidelines mandate that every Tg test have TgAb measured simultaneously and
      quantitatively by immunoassay and not a recovery test. The propensity and
      magnitude of TgAb-Tg interference relates to both Tg and TgAb concentrations and
      the class of Tg method used. Because the TgAb trend reflects changes in thyroid
      tissue mass, TgAb concentrations serve as a surrogate post-operative DTC tumor
      marker. A rising, or de novo appearance of TgAb may indicate recurrence, whereas
      a progressive decline suggests successful treatment. This review focuses on the
      technical limitations of current TgAb methods, characteristics of TgAb
      interference with different classes of Tg method, and the clinical value of
      monitoring TgAb trends as a surrogate DTC tumor marker. 

PMID- 24094641
TI  - Determination of catecholamines in plasma and urine.
AB  - For more than 20 years, measurement of catecholamines in plasma and urine in
      clinical chemistry laboratories has been the cornerstone of the diagnosis of
      neuroendocrine tumors deriving from the neural crest such as pheochromocytoma
      (PHEO) and neuroblastoma (NB), and is still used to assess sympathetic stress
      function in man and animals. Although assay of catecholamines in urine are still
      considered the biochemical standard for the diagnosis of NB, they have been
      progressively abandoned for excluding/confirming PHEOs to the advantage of
      metanephrines (MNs). Nevertheless, catecholamine determinations are still of
      interest to improve the biochemical diagnosis of PHEO in difficult cases that
      usually require a clonidine-suppression test, or to establish whether a patient
      with PHEO secretes high concentrations of catecholamines in addition to
      metanephrines. The aim of this chapter is to provide an update about the
      catecholamine assays in plasma and urine and to show the most common pre
      analytical and analytical pitfalls associated with their determination. 

PMID- 24094642
TI  - Determination of prolactin: the macroprolactin problem.
AB  - Serum prolactin is frequently measured when investigating patients with
      reproductive disorders and elevated concentrations are found in up to 17% of such
      cases. Clinical laboratories rely predominantly on automated analysers to
      quantify prolactin levels using sandwich immunometric methodologies. Though
      generally robust and reliable, such immunoassays are susceptible to interference
      from a high molecular mass prolactin/IgG autoantibody complex termed
      macroprolactin. While macroprolactin remains reactive to varying degrees in all
      prolactin immunoassays, it exhibits little if any biological activity in vivo and
      consequently its presence is considered clinically irrelevant.
      Macroprolactinaemia, defined as hyperprolactinaemia due to excess macroprolactin
      with normal concentrations of bioactive monomeric prolactin, may lead to
      misdiagnosis and mismanagement of hyperprolactinemic patients if not recognised.
      Current best practice recommends that all sera with elevated total prolactin
      concentrations are sub-fractionated using polyethylene glycol precipitation to
      provide a more meaningful clinical measurement of the bioactive monomeric
      prolactin content. Manufacturers of prolactin assays should strive to minimise
      interference from macroprolactin in their assays. Clinical laboratories should
      introduce screening procedures to exclude macroprolactinaemia in all patients
      identified as having hyperprolactinaemia. Clinicians should be aware of this
      potential diagnostic pit fall and insist on PEG screening of all
      hyperprolactinaemic sera. 

PMID- 24094643
TI  - Low radiation dose 256-MDCT angiography of the carotid arteries: effect of hybrid
      iterative reconstruction technique on noise, artifacts, and image quality.
AB  - To evaluate the effect of hybrid iterative reconstruction on qualitative and
      quantitative parameters at low dose carotid CTA. MATERIALS AND METHODS: 44
      consecutive patients were enrolled in the study. First group (n=22) was examined
      under 120 kV 250 mAs, second group (n = 22) - 100 kV 250 mAs. CT images in first
      group were reconstructed only with the filtered back projection (FBP). CT data in
      second group were reconstructed both with FBP and three levels of hybrid
      iterative reconstruction algorithm (iDose). We compared quantitative and
      qualitative parameters among the two groups and among four different
      reconstructions in second group. RESULTS: Effective dose in 120 kV and 100 kV
      group was 7.18 +/- 1.19 mSv and 4.14 +/- 1.03 mSv, respectively (p<0.0001). Mean
      arterial attenuation was about 25% higher in second group (236.5 +/- 46 HU vs.
      302.6 +/- 32.7 HU; p<0.0001). Image noise at the level of humeral belt was 32.5
      +/- 12.5 in 100 kV group and 26.3 +/- 13.3 in 120 kV (p = 0.115). Average noise
      decreased when using 3 levels of iDose up to 23.6 +/- 6.4, 17.7 +/- 5.6 and 13.7
      +/- 5.1, respectively (p = 0.00001). Mean CNR increased to 10.38 +/- 3.87, 14.5
      +/- 5.21 and 18.32 +/- 8.61, respectively (p<0.05). The presence of artifacts on
      the level of humeral belt in 120 kV group was 14%, in 100 kV - 41% (p = 0.002).
      The difference in visual scores between standard and low-dose protocol was
      significant (p = 0.008). When applying iterative reconstruction the frequency of
      streak artifacts decreased dramatically (p<0.0001). Most studies had excellent
      quality with no artifacts while using highest level of iDose. CONCLUSION:
      According to the results of our study low dose CT angiography using hybrid
      iterative reconstruction may provide sufficient image quality and allows for
      significant reduction of patient dose.

PMID- 24094644
TI  - Dynamic volume perfusion CT in patients with lung cancer: baseline perfusion
      characteristics of different histological subtypes.
AB  - OBJECTIVE: To evaluate dynamic volume perfusion CT (dVPCT) tumor baseline
      characteristics of three different subtypes of lung cancer in untreated patients.
      MATERIALS AND METHODS: 173 consecutive patients (131 men, 42 women; mean age 61
      +/- 10 years) with newly diagnosed lung cancer underwent dVPCT prior to biopsy.
      Tumor permeability, blood flow (BF), blood volume (BV) and mean transit time
      (MTT) were quantitatively assessed as well as tumor diameter and volume. Tumor
      subtypes were histologically determined and compared concerning their dVPCT
      results. dVPCT results were correlated to tumor diameter and volume. RESULTS:
      Histology revealed adenocarcinoma in 88, squamous cell carcinoma in 54 and small
      cell lung cancer (SCLC) in 31 patients. Tumor permeability was significantly
      differing between adenocarcinoma, squamous cell carcinoma and SCLC (all p<0.05).
      Tumor BF and BV were higher in adenocarcinomathan in SCLC (p = 0.001 and p=0.0002
      respectively). BV was also higher in squamous cell carcinoma compared to SCLC (p
      = 0.01). MTT was not differing between tumor subtypes. Regarding all tumors,
      tumor diameter did not correlate with any of the dVPCT parameters, whereas tumor
      volume was negatively associated with permeability, BF and BV (r = -0.22, -0.24, 
      0.24, all p<0.05). In squamous cell carcinoma, tumor diameter und volume
      correlated with BV (r = 0.53 and r = -0.40, all p<0.05). In SCLC, tumor diameter
      und volume correlated with MTT (r = 0.46 and r = 0.39, all p<0.05). In
      adenocarcinoma, no association between morphological and functional tumor
      characteristics was observed. CONCLUSIONS: dVPCT parameters are only partially
      related to tumor diameter and volume and are significantly differing between lung
      cancer subtypes.

PMID- 24094645
TI  - Acute epididymitis in ultrasound: results of a prospective study with baseline
      and follow-up investigations in 134 patients.
AB  - OBJECTIVES: To perform a comprehensive follow-up analysis of ultrasonographic
      scrotal features and associated signs in patients with acute epididymitis.
      METHODS: Between 2007 and 2012, 134 adults (median age 54 years) with acute
      epididymitis underwent scrotal ultrasonography and palpation at first
      presentation and after 2 weeks and 3 months. RESULTS: At first presentation, 61
      patients (45.5%) had hydrocele, 63 (47.0%) concomitant orchitis, and 8 (5.9%)
      epididymal abscess. Epididymitis was predominantly located in 24 cases (17.9%) in
      the head, 52 cases (38.8%) in the tail, and 58 cases (43.3%) in both. On the
      affected side, testicular volume was 16.9 +/- 6.8 ml and peak systolic velocity
      of the testicular artery was 23.7 +/- 7.5 cm/s, compared to the healthy side with
      12.3 +/- 4.4 ml and 9.5 +/- 3.6 cm/s respectively (P<0.001). Concomitant orchitis
      was associated with hydrocele, testicular enlargement and pain (P<0.01).
      Orchiectomy due to secondary testicular infarction was necessary in four cases,
      while in all other patients ultrasound parameters normalized. Only 16/90 patients
      (17.8%) showed a persistent epididymal swelling after 3 months. CONCLUSIONS:
      Common ultrasound features include hydrocele, epididymal enlargement,
      hyperperfusion, and testicular involvement. Under conservative treatment,
      ultrasound parameters normalize without evidence of testicular atrophy even in
      patients with epididymal abscess or concomitant orchitis.

PMID- 24094646
TI  - Prevalence of sarcopenia in community-dwelling Japanese older adults.
AB  - BACKGROUND: Sarcopenia, the age-dependent loss of skeletal muscle mass, is highly
      prevalent among older adults in many countries; however, the prevalence of
      sarcopenia in healthy Japanese community-dwelling older adults is not well
      characterized. OBJECTIVE: The aim of this study was to evaluate the prevalence of
      sarcopenia and to examine the association of sarcopenia with falls and fear of
      falling in community-dwelling Japanese older adults. DESIGN: This is a cross
      sectional study. SETTING AND SUBJECTS: Healthy men (568) and women (1314) aged 65
      to 89 years participated in this research. MEASUREMENTS: For all participants, 3
      measurements were taken: skeletal muscle mass measurement using bioelectrical
      impedance, 10 m at a usual walking speed, and handgrip strength. Sarcopenia was
      defined as the presence of both poor muscle function (low physical performance or
      low muscle strength) and low muscle mass. RESULTS: The prevalence of sarcopenia,
      determined using the European Working Group on Sarcopenia in Older People
      suggested algorithm, in men and women aged 65 to 89 years was 21.8% and 22.1%,
      respectively. The prevalence of sarcopenia increased age-dependently, especially
      in those older than 75 years in both genders. In the young old, the prevalence of
      sarcopenia was higher in women than in men; however, in those older than 85
      years, the prevalence of sarcopenia was lower in women than in men (P < .05). In
      addition, fall incidents and fear of falling were more prevalent in sarcopenic
      older adults than in nonsarcopenic older adults (P < .05). CONCLUSIONS: These
      results suggest that sarcopenia is highly prevalent in community-dwelling
      Japanese older adults and is related to falls and fear of falling.

PMID- 24094647
TI  - Cholesterol, statins, and longevity from age 70 to 90 years.
AB  - BACKGROUND: The importance of cholesterol as a risk factor among older people,
      particularly among the very old, is controversial. Whether or not
      hypercholesterolemia warrants medical concern, and whether statins are beneficial
      among very old people, remain unresolved common clinical dilemmas. This study
      examines whether increased total cholesterol (TC) was associated with higher
      mortality from age 70 to 90, and if statins had a protective effect. METHODS: A
      representative sample (born 1920-1921) from the Jerusalem Longitudinal Cohort
      Study (1990-2010) was assessed at ages 70, 78, and 85 for fasting serum TC, low
      density (LDL), and high-density lipoprotein (LDL); triglycerides; statin usage;
      social, functional, and medical domains; and all-cause mortality data (1990
      2010). TC was analyzed as either continuous (10 mg/dL increments) or dichotomous
      variable (high TC >200 mg/dL). Cox proportional hazards models determined
      mortality hazard ratios (HRs), adjusting for TC, statin treatment, gender, self
      rated health, smoking, hypertension, diabetes, ischemic heart disease, neoplasm,
      body mass index, albumin, and triglycerides. RESULTS: Prevalence of high TC at
      ages 70, 78, and 85 was 75% (n = 344), 65% (n = 332), and 34% (n = 237), and
      statin use was 0%, 17.9%, and 45.4%, respectively. Survival was increased (not
      significantly) among subjects with high TC >200 mg/dL versus <=200 mg/dL from
      ages 70 to 78, 78 to 85, and 85 to 90: 79.1% versus 73.3% (log rank P = .16),
      68.7% versus 61.5% (P = .10), and 73.4% versus 70.3% (P = .45), respectively.
      Survival was significantly increased among subjects treated with statins versus
      no statins at ages 78 to 85 (74.7% vs 64.3%, log rank P = .07) and 85 to 90
      (76.2% vs 67.4%, P = .01). After adjustment, TC (continuous or dichotomous) was
      not associated with mortality from 70 to 78, 78 to 85, or 85 to 90. In contrast,
      statins at age 85 were associated with decreased mortality from age 85 to 90
      (adjusted HR 0.61, 95% confidence interval 0.42-0.89). CONCLUSIONS: Among older
      people, cholesterol levels were unrelated to mortality between the ages of 70 and
      90. The protective effect of statins observed among the very old appears to be
      independent of TC.

PMID- 24094648
TI  - Characterization of nanoporous carbon fibrous materials obtained by chemical
      activation of plane tree seed under ultrasonic irradiation.
AB  - An ultrasonic irradiation was applied for the impregnation by chemical agents in
      the chemical activation process of new type of active carbon precursor. Plane
      tree seed, due to the unique fibrous structure and low cost is a promising eco
      friendly raw material for the preparation of activated carbon materials.
      Ultrasonic irradiation was used for the impregnation step allowing the chemical
      activation by different agents: potassium or sodium hydroxide, hydrogen peroxide
      and pyrogallol. The porous structures were examined by nitrogen
      adsorption/desorption isotherms at 77 K and electrochemically by cyclic
      voltammetry. The textures of these materials were observed by scanning electron
      microscopy. The application of ultrasonic irradiation in the impregnation step
      increased surface area of the final material more than two times in comparison to
      the material which impregnation in the activation process was by conventional
      stirring. Ultrasonic irradiation enhances the chemical activation process and the
      activated carbon fibrous materials with nanoporous structure were obtained by
      impregnation of seeds with alkaline hydroxides. Total surface areas of these
      samples were 976 m(2) g(-1) and 1130 m(2) g(-1). These fibers have total specific
      capacitance as high as 125 F g(-1) and 53 F g(-1) which major fraction in both
      cases originate from internal micropores structure.

PMID- 24094649
TI  - Numerical simulation of ultrasonic enhancement on mass transfer in liquid-solid
      reaction by a new computational model.
AB  - Mass transfer coefficient is an important parameter in the process of mass
      transfer. It can reflect the degree of enhancement of mass transfer process in
      liquid-solid reaction and in non-reactive systems like dissolution and leaching,
      and further verify the issues by experiments in the reaction process. In the
      present paper, a new computational model quantitatively solving ultrasonic
      enhancement on mass transfer coefficient in liquid-solid reaction is established,
      and the mass transfer coefficient on silicon surface with a transducer at
      frequencies of 40 kHz, 60 kHz, 80 kHz and 100 kHz has been numerically simulated.
      The simulation results indicate that mass transfer coefficient increases with the
      increasing of ultrasound power, and the maximum value of mass transfer
      coefficient is 1.467 * 10(-4) m/s at 60 kHz and the minimum is 1.310 * 10(-4) m/s
      at 80 kHz in the condition when ultrasound power is 50 W (the mass transfer
      coefficient is 2.384 * 10(-5) m/s without ultrasound). The extrinsic factors such
      as temperature and transducer diameter and distance between reactor and
      ultrasound source also influence the mass transfer coefficient on silicon
      surface. Mass transfer coefficient increases with the increasing temperature,
      with the decreasing distance between silicon and central position, with the
      decreasing of transducer diameter, and with the decreasing of distance between
      reactor and ultrasound source at the same ultrasonic power and frequency. The
      simulation results indicate that the computational model can quantitatively solve
      the ultrasonic enhancement on mass transfer coefficient.

PMID- 24094651
TI  - Comparison of optics and performance of a distal sensor high definition
      cystoscope, a distal sensor standard definition cystoscope, and a fiberoptic
      cystoscope.
AB  - OBJECTIVE: To evaluate performance characteristics and optics of a new generation
      high-definition distal sensor (HD-DS) flexible cystoscope, a standard-definition
      distal sensor (SD-DS) cystoscope, and a standard fiberoptic (FO) cystoscope.
      METHODS: Three new cystoscopes (HD-DS, SD-DS, and FO) were compared for active
      deflection, irrigation flow, and optical characteristics. Each cystoscope was
      evaluated with an empty working channel and with various accessories. Optical
      characteristics (resolution, grayscale imaging, color representation, depth of
      field, and image brightness) were measured using United States Air Force
      (USAF)/Edmund Optics test targets and illumination meter. We digitally recorded a
      porcine cystoscopy in both clear and blood fields, with subsequent video analysis
      by 8 surgeons via questionnaire. RESULTS: The HD-DS had a higher resolution than
      the SD-DS and the FO at both 20 mm (6.35 vs 4.00 vs 2.24 line pairs/mm) and 10 mm
      (14.3 vs 7.13 vs 4.00 line pairs/mm) evaluations, respectively (P <.001 and P
      <.001). Color representation and depth of field (P = .001 and P <.001) were
      better in the HD-DS. When compared to the FO, the HD-DS and SD-DS demonstrated
      superior deflection up and irrigant flow with and without accessory present in
      the working channel, whereas image brightness was superior in the FO (P <.001, P
      = .001, and P <.001, respectively). Observers deemed the HD-DS cystoscope
      superior in visualization in clear and bloody fields, as well as for
      illumination. CONCLUSION: The new HD-DS provided significantly improved
      visualization in a clear and a bloody field, resolution, color representation,
      and depth of field compared to SD-DS and FO. Clinical correlation of these
      findings is pending.

PMID- 24094650
TI  - The epithelial cell-derived atopic dermatitis cytokine TSLP activates neurons to
      induce itch.
AB  - Atopic dermatitis (AD) is a chronic itch and inflammatory disorder of the skin
      that affects one in ten people. Patients suffering from severe AD eventually
      progress to develop asthma and allergic rhinitis, in a process known as the
      "atopic march." Signaling between epithelial cells and innate immune cells via
      the cytokine thymic stromal lymphopoietin (TSLP) is thought to drive AD and the
      atopic march. Here, we report that epithelial cells directly communicate to
      cutaneous sensory neurons via TSLP to promote itch. We identify the ORAI1/NFAT
      calcium signaling pathway as an essential regulator of TSLP release from
      keratinocytes, the primary epithelial cells of the skin. TSLP then acts directly
      on a subset of TRPA1-positive sensory neurons to trigger robust itch behaviors.
      Our results support a model whereby calcium-dependent TSLP release by
      keratinocytes activates both primary afferent neurons and immune cells to promote
      inflammatory responses in the skin and airways. 

PMID- 24094652
TI  - Assessment of deoxyribonucleic acid fragmentation index, testicular volume, semen
      parameters, and hormone profile in gonadotropin-treated men with hypogonadotropic
      hypogonadism.
AB  - OBJECTIVE: To study the sperm deoxyribonucleic acid (DNA) fragmentation index
      (DFI), testicular volume, semen parameters, and hormone profile in human
      chorionic gonadotropin (hCG)- and human menopausal gonadotrophin (hMG)-treated
      patients with hypogonadotropic hypogonadism (HH) with and without a successful
      pregnancy. METHODS: This is a cross sectional study. The study initially included
      81 patients with HH and azoospermia at the Infertility Unit of Royan Institute
      between 2010 and 2012. Fifty-eight of 81 patients achieved >1 * 10(6) sperm/mL
      during hCG and hMG therapy. These 58 patients were divided into the following 2
      groups: 20 patients with HH who achieved pregnancy in response to hCG/hMG
      (responders, 16 naturally and 4 by intrauterine insemination) and 38 gonadotropin
      treated patients with HH with failed pregnancy (nonresponders, 29 naturally, 5 by
      intrauterine insemination, 1 by in vitro fertilization, and 3 by intracytoplasmic
      sperm injection). Sperm DNA fragmentation was visualized by terminal
      deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) assay. RESULTS:
      Average of DFI (responders: 13.45 +/- 0.64; nonresponders: 21.92 +/- 0.86), age,
      body mass index, testis volume semen parameters, and follicle-stimulating
      hormone, luteinizing hormone, and testosterone levels in the 2 groups were
      calculated. Cut-off point for DFI was determined by receiver operating curve
      analysis (17.5%). CONCLUSION: It was shown that DFI in responders is
      significantly lower than DFI in nonresponders (P <.001), and duration of hCG and
      hMG therapy in responders is significantly higher than those of nonresponders (P
      <.05). DFI could be predictive of conception (P <.001; odds ratio 0.57; 95%
      confidence interval 0.417-0.778). It can be concluded that despite low sperm
      quality, especially sperm concentration in these patients, decreasing sperm DNA
      damage may result in successful fertilization.

PMID- 24094653
TI  - Editorial comment.

PMID- 24094654
TI  - Reply: To PMID 24094653.

PMID- 24094655
TI  - Right renal vein extension with cryopreserved external iliac artery allografts in
      living-donor kidney transplantations.
AB  - INTRODUCTION: A short right renal vein remains a challenge for renal transplant
      surgery, especially in the living donor. Our objective was to report on a new
      technique to solve this problem. TECHNICAL CONSIDERATIONS: We describe our
      experience with the use of cryopreserved iliac artery grafts for right renal vein
      extension. Two renal grafts from living donors with a short right renal vein were
      subjected to an extension with a cryopreserved external iliac artery allograft.
      There were no perioperative or postoperative complications. There were also no
      changes in ischemia times. The renal implantation was performed easily and
      conveniently using our standard technique. For the first and second procedures,
      at 3 and 3.5 years after surgery, respectively, both vascular grafts maintain
      good patency, and the renal function of both recipients is optimal. CONCLUSION:
      Tissue-banked cryopreserved cadaveric vessels can be a useful tool in renal
      transplant surgery. The use of a cryopreserved iliac artery for renal vein
      extension is a simple and effective new technique that can be added to the pool
      of surgical solutions for a short renal vein in living-donor kidney
      transplantation. To our knowledge, this is the first time that the use of such
      grafts for this purpose has been described.

PMID- 24094656
TI  - Primary retroperitoneal lymph node dissection in low-stage testicular germ cell
      tumors: a detailed pathologic study with clinical outcome analysis with special
      emphasis on patients who did not receive adjuvant therapy.
AB  - OBJECTIVE: To evaluate, in detail, the histopathologic features of metastatic
      testicular germ cell tumors to retroperitoneal lymph nodes treated with primary
      retroperitoneal lymph node dissection (RPLND) and correlate the findings with
      patients' outcomes. MATERIALS AND METHODS: We studied 183 patients with
      documented pathologic stage II disease with or without elevated serum tumor
      markers, selected from 453 patients who underwent primary RPLND at our
      institution from 1989 to 2002. Tumor type(s), size and extent of disease, and
      amount of tumor necrosis were assessed and correlated with outcome. RESULTS:
      Embryonal carcinoma was the most common tumor type, present as the only component
      in 99 cases (54%) and the predominant tumor type (>50%) in 142 (78%). The number
      of positive lymph nodes ranged from 1 to 40 from a total of 2-80 lymph nodes
      examined (median, 28). Extranodal extension (ENE) was identified in 120 cases
      (66%). Among 73 patients followed up expectantly and with normal serum tumor
      markers, 19 experienced relapse, the probability of which was higher in patients
      with more positive nodes, larger metastases, and presence of ENE. However, none
      of these differences was statistically significant (all P >.2). The predominance
      of embryonal carcinoma and the presence of tumor necrosis were not significantly
      associated with outcome. CONCLUSION: In this cohort, most patients treated with
      primary RPLND and with positive lymph nodes also had ENE. We did not identify any
      variables to be significantly associated with relapse after RPLND in patients
      managed expectantly. Additional studies with more patients are needed to validate
      our findings.

PMID- 24094657
TI  - Urinary outcomes are significantly affected by nerve sparing quality during
      radical prostatectomy.
AB  - OBJECTIVE: To assess the effect of nerve sparing (NS) quality on self-reported
      patient urinary outcomes after radical prostatectomy. METHODS: A total of 102
      preoperatively potent men underwent laparoscopic or robotic radical
      prostatectomy; NS was prospectively graded at surgery using a 0-4
      scale/neurovascular bundle. Urinary functional outcomes were measured by
      validated Expanded Prostate Cancer Index Composite questionnaire at baseline and
      follow-up time points (1, 3, 6, 9, and 12 months) in 99 men who underwent various
      degrees of NS. Mixed linear regression was used to analyze the effect of NS
      quality and other clinical factors on urinary outcomes. RESULTS: Patients with at
      least 1 neurovascular bundle spared completely, along with its supportive tissues
      (NS grade 4/4), noted significantly improved Expanded Prostate Cancer Index
      Composite urinary functional and continence outcomes as early as 1 month
      postoperatively and up to 12 months. Significantly less urinary bother was also
      noted in these men by 9-12 months postoperatively. Multivariate analysis revealed
      that bilateral or unilateral excellent NS (at least 1 bundle graded 4/4),
      increasing time from surgery, young patient age, and lower body mass index
      positively and significantly affected urinary functional outcomes, including pad
      use. Men who received excellent unilateral NS recovered urinary function about as
      well as men who had both neurovascular bundles spared in similar fashion.
      CONCLUSION: The quality of NS significantly influences patient-defined urinary
      functional convalescence. Completely sparing at least 1 neurovascular bundle
      along with its supportive tissues has a dramatic effect on the recovery of
      urinary continence and quality of life in preoperatively potent men.

PMID- 24094658
TI  - Three-dimensional vs standard laparoscopy: comparative assessment using a
      validated program for laparoscopic urologic skills.
AB  - OBJECTIVE: To compare the last generation of 3-dimensional imaging (3D) vs
      standard 2-dimensional imaging (2D) laparoscopy. MATERIALS AND METHODS: A
      prospective observational study was conducted during the 4th Minimally Invasive
      Urological Surgical Week Course held in Braga (Portugal) in April 2013. The
      course participants and faculty were asked to perform standardized tasks in the
      dry laboratory setting and randomly assigned into 2 study groups; one starting
      with 3D, the other with 2D laparoscopy. The 5 tasks of the European Training in
      Basic Laparoscopic Urological Skills were performed. Time to complete each task
      and errors made were recorded and analyzed. An end-of-study questionnaire was
      filled by the participants. RESULTS: Ten laparoscopic experts and 23 laparoscopy
      naive residents were included. Overall, a significantly better performance was
      obtained using 3D in terms of time (1115 seconds, interquartile range [IQR] 596
      1469 vs 1299 seconds, IQR 620-1723; P = .027) and number of errors (2, IQR 1-3 vs
      3, IQR 2-5.5; P = .001). However, the experts were faster only in the "peg
      transfer" task when using the 3D, whereas naives improved their performance in 3
      of the 5 tasks. A linear correlation between level of experience and performance
      was found. Three-dimensional imaging was perceived as "easier" by a third of the
      laparoscopy-naive participants (P = .027). CONCLUSION: Three-dimensional imaging
      seems to facilitate surgical performance of urologic surgeons without
      laparoscopic background in the dry laboratory setting. The advantage provided by
      3D for those with previous laparoscopic experience remains to be demonstrated.
      Further studies are needed to determine the actual advantage of 3D over standard
      2D laparoscopy in the clinical setting.

PMID- 24094659
TI  - Editorial comment.

PMID- 24094660
TI  - Editorial comment.

PMID- 24094661
TI  - Reply: To PMID 24094657.

PMID- 24094662
TI  - Editorial comment.

PMID- 24094663
TI  - The correlation of biochemical and morphologic parameters in the assessment of
      sperm maturity.
AB  - OBJECTIVE: To examine the relationship between biochemical markers and
      morphologic sperm characteristics, including head, neck, and tail changes.
      METHODS: The study evaluated 154 patients who went to the Andrology Laboratory of
      the Clinic of Urology, Clinical Center of Serbia. Patients were divided into 4
      groups: normozoospermic, oligozoospermic, severe oligozoospermic, and
      asthenozoospermic, according to the sperm concentration and motility. RESULTS:
      The differences in creatine kinase (CK) and CK-M levels between normozoospermic
      and the 2 groups of oligozoospermic patients were significantly different (P
      <.01). The CK and CK-M levels correlated negatively with sperm concentration and
      sperm motility, but correlated positively with the pathologic sperm form.
      Patients with CK values >0.093 have a total number of pathologic forms higher
      than 0.40 (87.5% sensitivity, 77.3% specificity, the area under the curve was
      0.832, P <.001). Patients with CK values <0.09 U/L have normal spermatogenesis
      and pathologic disorder of the head <15%, neck <12%, and tail <10%. CONCLUSION:
      The relation between sperm morphology and biochemical markers included in the
      maturation process is established during the sperm genesis process. If the
      results of these markers are used together with the morphology of the spermatozoa
      in the interpretation of infertility, it would lead us to better insight of the
      fertility potential of the each patient.

PMID- 24094664
TI  - [Razemon's lateral digital rotation flap in severe Dupuytren contracture of the
      fifth finger].
AB  - In Dupuytren's disease, correction of severe contracture deformities and excision
      of dermal lesions are often responsible for palmar skin defects. This study aimed
      to assess the results of the lateral digital flap described by Razemon. Thirty
      seven patients were analysed retrospectively for functional and trophic results.
      Twelve months of follow-up were at least required. The lack of extension was
      appreciated through Thomine's coefficient. Subjective patient's opinion was noted
      about function of fifth finger and hand. The flap trophicity was evaluated
      through softness, coverage quality and esthetic aspect. In the preoperative
      period, the average lack of extension was 105 degrees ; 89% of the patients were
      ranked as stages 3 or 4 of Tubiana's classification. At the 12th month, the
      average Thomine's coefficient was 0.74; 70% of the patients were very satisfied.
      Two patients exhibited some lack of suppleness and seven a dyschromic scars. The
      lateral digital rotation flap is a quite simple surgical procedure. It allows
      satisfactory results corresponding to functional and trophic coverage in severe
      Dupuytren's contracture involving the fifth finger. 

PMID- 24094666
TI  - [Fatal hemorrhage in postpartum by rupture of a splenic artery aneurysm].
AB  - The maternal mortality is rare and when it arises, the family often puts the
      medical profession in guilty's position. We present the case of a 38-year-old
      woman, died in the post-partum in a context of intense back pains. The autopsy
      found an incidental hemorrhagic syndrome to a two-stage rupture of the splenic
      artery. We shall discuss the aetiology. The autopsy and the anatomopathological
      examination are practiced only in hardly more than a quarter of the cases while
      they will be important in proceedings and will allow the family to go into
      mourning. 

PMID- 24094665
TI  - Pre-gestational versus gestational diabetes: a population based study on clinical
      and demographic differences.
AB  - AIMS: To assess the clinical and demographic differences in patients with pre
      gestational diabetes mellitus (PGDM) compared to those with gestational diabetes
      (GDM). METHODS: Using the 2001-2007 California Health Discharge Database, we
      identified 22,331 cases of PGDM and 147,097 cases of GDM via ICD-9-CM codes after
      excluding cases which were missing race or age data or with extremes of age. Data
      analyzed included demographics, pre-existing medical conditions, antepartum
      complications, and intrapartum complications. Logistic regression was used to
      adjust for potential confounders. RESULTS: Both PGDM and GDM incidences increased
      during the study period. Advancing age was associated with increased prevalence
      of both diseases. Although Asians were found to have the highest prevalence of
      GDM, they, along with Caucasians, were found have the lowest prevalence of PGDM.
      Conditions with increased frequency in PGDM versus GDM included chronic
      hypertension, renal disease, thyroid dysfunction, fetal CNS malformation, fetal
      demise, pyelonephritis, and eclampsia. Subjects with PGDM were more likely than
      those with GDM to have a shoulder dystocia, failed induction of labor, or undergo
      cesarean delivery. CONCLUSIONS: We have demonstrated clinical morbidities and
      demographic factors which differ in patients with PGDM compared to patients with
      GDM. Our findings suggest PGDM to be associated with significantly higher
      morbidity when compared to GDM. Our findings also suggest that races with the
      highest tendency for GDM during pregnancy may not necessarily have the highest
      tendency for PGDM outside of pregnancy.

PMID- 24094667
TI  - [Chemotherapy in epithelial ovarian cancer].
AB  - Chemotherapy is fundamental in the management of epithelial ovarian carcinomas
      both for early and advanced stages (rarely surgical treatment alone) and in
      almost every step of the disease. The reference schema combines carboplatin and
      paclitaxel intravenously. Intraperitoneal chemotherapy also proved its efficacy
      after complete surgery for advanced disease and should be reserved to trained
      teams due to its technical constraints and toxicity issues. Modalities of
      treatment in relapsed and progressive disease depend mainly on the free interval
      between this diagnosis and the last dose of platinum. Bevacizumab has proven its
      effectiveness in prolonging progression-free survival in 1st line setting in
      association with chemotherapy followed by maintenance and in case of relapse or
      progression both fore platinum sensitive or resistant disease. Finally, a better
      understanding of ovarian cancer biology will allow us to consider new molecular
      targeted agents guided by the specific characteristics of each patient and each
      tumor. 

PMID- 24094668
TI  - Estimating stature in South African populations using various measures of the
      sacrum.
AB  - The accurate estimation of stature can meaningfully contribute to the positive
      identification of skeletal remains of unknown individuals. Regression equations
      are most commonly used to estimate stature and have been derived from numerous
      bones. Little is however known about stature estimation from the sacrum and
      therefore the aim of the current study was to evaluate whether it is possible to
      estimate stature from various sacral measurements in South African populations. A
      total of 210 sacra representing 50 black males, 51 white males, 58 black females
      and 51 white females were measured. These measurements included anterior sacral
      height, anterior sacral width, maximum transverse diameter of the base, anterior
      sacral height of individual sacral segments (S1, S2, S3, S4, S5) as well as
      combinations of anterior sacral heights of segments, (i.e. S1+S2). The
      correlation of these measures to stature was calculated using Pearson's
      correlation coefficient, followed by the calculation of linear least square and
      multiple regression equations for the estimation of stature. Statistical analyses
      indicated differences between sexes and population groups with multiple
      regressions being slightly more accurate than regression equations derived from
      single variables. Standard error of estimate values for the present study fall
      within the ranges stated by previous researchers, with smaller stature estimation
      intervals reported for black South Africans and females. This study suggests that
      regression equations derived from the sacrum of South Africans can be used to
      calculate reasonable estimates of stature, in the absence of bones that yield
      more accurate results. 

PMID- 24094669
TI  - [Conclusion. Facial reconstructive surgery].

PMID- 24094670
TI  - Re: "Treatment of low subcondylar fractures--a 5-year retrospective study".

PMID- 24094671
TI  - Progressive multifocal leukoencephalopathy of the brainstem in an immunocompetent
      patient--JC and BK polyoma-virus coinfection? A case report and review of the
      literature.

PMID- 24094672
TI  - Quantitative assessment of lipiodol deposition after chemoembolization:
      comparison between cone-beam CT and multidetector CT.
AB  - PURPOSE: To evaluate the ability of cone-beam computed tomography (CBCT)
      performed directly after transarterial chemoembolization to assess ethiodized oil
      (Lipiodol) deposition in hepatocellular carcinoma (HCC) and compare it with
      unenhanced multidetector computed tomography (CT). MATERIALS AND METHODS:
      Conventional transarterial chemoembolization was used to treat 15 patients with
      HCC, and CBCT was performed to assess Lipiodol deposition directly after
      transarterial chemoembolization. Unenhanced multidetector CT was performed 24
      hours after transarterial chemoembolization. Four patients were excluded because
      the margin of tumor or area of Lipiodol deposition was unclear. The image
      enhancement density of the entire tumor and liver parenchyma was measured by
      ImageJ software, and tumor-to-liver contrast (TLC) was calculated. In addition,
      volumetric measurement of tumor and Lipiodol was performed by semiautomatic three
      dimensional volume segmentation and compared using linear regression to evaluate
      consistency between the two imaging modalities. RESULTS: The mean value of TLC on
      CBCT was not significantly different from TLC on multidetector CT (337.7 HU +/-
      233.5 vs 283.0 HU +/- 152.1, P = .103).The average volume of the whole tumor and
      of only the regions with Lipiodol deposition and the calculated average
      percentage of Lipiodol retention on CBCT were not significantly different
      compared with multidetector CT (tumor volume, 9.6 cm(3) +/- 11.8 vs 10.8 cm(3) +/
      14.2, P = .142; Lipiodol volume, 6.3 cm(3) +/- 7.7 vs 7.0 cm(3) +/- 8.1, P =
      .214; percentage of Lipiodol retention, 68.9% +/- 24.0% vs 72.2% +/- 23.1%, P =
      .578). Additionally, there was a high correlation in the volume of tumor and
      Lipiodol between CBCT and multidetector CT (R(2) = 0.919 and 0.903). CONCLUSIONS:
      The quantitative image enhancement and volume analyses demonstrate that CBCT is
      similar to multidetector CT in assessing Lipiodol deposition in HCC after
      transarterial chemoembolization.

PMID- 24094673
TI  - Effect of real-time radiation dose feedback on pediatric interventional radiology
      staff radiation exposure.
AB  - PURPOSE: To measure and compare individual staff radiation dose levels during
      interventional radiologic (IR) procedures with and without real-time feedback to
      evaluate whether it has any impact on staff radiation dose. MATERIALS AND
      METHODS: A prospective trial was performed in which individuals filling five
      different staff roles wore radiation dosimeters during all IR procedures during
      two phases: a 12-week "closed" phase (measurements recorded but display was off,
      so no feedback was provided) and a 17-week "open" phase (display was on and
      provided real-time feedback). Radiation dose rates were recorded and compared by
      Mann-Whitney U test. RESULTS: There was no significant difference in median
      procedure time, fluoroscopy time, or patient dose (dose-area product normalized
      to fluoroscopy time) between the two phases. Overall, the median staff dose was
      lower in the open phase (0.56 uSv/min of fluoroscopy time) than in the closed
      phase (3.01 uSv/min; P < .05). The IR attending physician dose decreased
      significantly for procedures for which the physicians were close to the patient,
      but not for ones for which they were far away. CONCLUSIONS: A radiation dose
      monitoring system that provides real-time feedback to the interventional staff
      can significantly reduce radiation exposure to the primary operator, most likely
      by increasing staff compliance with use of radiation protection equipment and
      dose reduction techniques.

PMID- 24094674
TI  - Comparison of primary jejunostomy tubes versus gastrojejunostomy tubes for
      percutaneous enteral nutrition.
AB  - PURPOSE: To evaluate technical success and long-term outcomes of percutaneous
      primary jejunostomy tubes for postpyloric enteral feeding compared with
      percutaneous gastrojejunostomy (GJ) tubes. MATERIALS AND METHODS: Over a 25-month
      interval, 41 consecutive patients (26 male; mean age, 55.9 y) underwent attempted
      fluoroscopy-guided direct percutaneous jejunostomy tube insertion. Insertions at
      previous jejunostomy tube sites were excluded. The comparison group consisted of
      all primary GJ tube insertions performed over a 12-month interval concomitant
      with the jejunostomy tube interval (N = 169; 105 male; mean age, 59.4 y).
      Procedural, radiologic, and clinical data were retrospectively reviewed.
      Intervention rates were expressed as events per 100 catheter-days. RESULTS: The
      technical success rate for percutaneous jejunostomy tube insertion was 96%,
      versus 93% for GJ tubes (P = .47). Mean fluoroscopy times were similar for
      jejunostomy and GJ tubes (9.8 vs 10.0 min, respectively; P value not
      significant). Jejunostomy tubes exhibited a lower rate of catheter dysfunction
      than GJ tubes, with catheter exchange rates of 0.24 versus 0.93, respectively,
      per 100 catheter-days (P = .045). GJ tube tip retraction into the stomach
      occurred in 9.5% of cases, at a rate of 0.21 per 100 catheter-days. Intervention
      rates related to leakage were 0.19 and 0.03 for jejunostomy and GJ tubes,
      respectively (P < .01). Jejunostomy and GJ tubes exhibited similar rates of
      catheter exchange for occlusion and replacement as a result of inadvertent
      removal. No major complications were encountered in either group. CONCLUSIONS:
      Percutaneous insertion of primary jejunostomy tubes demonstrated technical
      success and complication rates similar to those of GJ tubes. Jejunostomy tubes
      exhibited a lower dysfunction rate but a higher leakage rate compared with GJ
      tubes.

PMID- 24094675
TI  - [Inappropriate prescribing of drugs in older people attending primary care health
      centres: detection using STOPP-START criteria].
AB  - OBJECTIVE: To determine the prevalence and characteristics of inappropriate
      prescribing of drugs (IP) in patients >65 years-old evaluated by a primary care
      team (PCT), using the STOPP-START criteria. MATERIAL AND METHOD: Cross-sectional
      sample of patients older than 65 years-old with active clinical history in 2010,
      and who were attended in 13 urban clinics (systematic random sampling, expected
      IP prevalence of 40%, precision: 5% confidence level: 95%). Requirement was
      reviewed clinical histories in 2010, using the STOPP-START criteria. RESULTS: A
      total of 363 patients were selected (56.7% women), mean age 75.2 years (SD:
      7.02). The most frequent diseases were cardiovascular (76.9%) and osteoarticular
      (57.6%) diseases, and the average number of prescription drugs was 4.9 (SD:
      3.32). IP was detected in 170 patients (46.8%; 95% CI: 41.7-52.0%), 42% in men
      (95% CI: 34.3-49.8%) and 46.6% in women (95% CI: 39.8-53.4%), with no differences
      between sexes (P=.386), with a higher prevalence if polypharmacy or comorbidity
      were present (P<.001). The STOPP criteria were met in 131 patients (36.1%; 95%
      CI: 31.1-41.0%), and START criteria in 73 (20.1%; 95% CI: 16-24.2%), with no
      difference between sexes (P=.623 for STOPP, and P=.678 for START). The most
      frequent STOPP criteria were observed in the musculoskeletal system (50 patients,
      38.2%; 95% CI: 29.8-46.5%) and START endocrinology indicators (38 patients,
      52.1%; 95% CI: 40.0-63.9%). CONCLUSIONS: The STOPP-START tool detected and
      systematised IP in a high percentage of elderly patients treated by a PCT, and
      can promote improvement in prescribing strategies.

PMID- 24094676
TI  - [Arteriovenous thrombosis as a first sign of antiphospholipid syndrome in an
      octogenarian patient].

PMID- 24094677
TI  - [Frailty as a predictor of adverse events in epidemiological studies: literature
      review].
AB  - Several epidemiological studies have analyzed the association between frailty
      status and adverse geriatric health outcomes, with there being a clear
      relationship being demonstrated in mortality, disability, mobility loss,
      institutionalization and falls. However, different studies have evaluated
      different number of these adverse events, with different criteria, and with
      different follow-up periods. As a result of this relationship, the objective of
      geriatric medicine must not only be the prevention, diagnosis and treatment of
      diseases based on multidisciplinary team work and use of geriatric units
      according to functional status of patients, but the detection, prevention and
      treatment of frailty. Frailty must be considered as a pre-disability state that
      can be prevented and treated to delay its progression towards disability,
      institutionalization, and death. The characterization of frailty status can also
      help other medical specialties to stratify the risk of adverse health outcomes in
      oncology treatments, surgical interventions, or diagnostic procedures. 

PMID- 24094678
TI  - Developing Research Domain Criteria (RDoC) to improve diagnosis and treatment of
      social deficits in psychiatric disorders: the Mirror Neuron System as a model.

PMID- 24094680
TI  - The attenuated psychosis syndrome in DSM-5.

PMID- 24094679
TI  - Sleep dysfunction and thalamic abnormalities in adolescents at ultra high-risk
      for psychosis.
AB  - BACKGROUND: Sleep dysfunction is a pervasive, distressing characteristic of
      psychosis, yet little is known regarding sleep quality prior to illness onset. At
      present, it is unclear whether sleep dysfunction precedes the emergence of
      psychotic symptoms, signifying a core feature of the disorder, or if it
      represents a consequence of prolonged contact with aspects of schizophrenia and
      its treatment (e.g., medication use or neurotoxicity) or co-morbid symptoms
      (e.g., depressive and manic symptomatology). The current study examined sleep
      dysfunction in adolescents at ultra high-risk (UHR) for psychosis, relationships
      between sleep disturbances and psychosis symptoms, volume of an integral sleep
      structure (thalamus), and associations between thalamic abnormalities and sleep
      impairment in UHR youth. METHOD: Thirty-three UHR youth and 33 healthy controls
      (HC) participated in a self-assessment of sleep functioning (Pittsburgh Sleep
      Quality Index; PSQI), self and parent-report clinical interviews, and structural
      magnetic resonance imaging (MRI). RESULTS: UHR adolescents displayed increased
      latency to sleep onset and greater sleep disturbances/disrupted continuity
      compared to HC youth, over and above concurrent mood symptoms. Among UHR youth,
      increased sleep dysfunction was associated with greater negative symptom severity
      but not positive symptoms. Compared to HC adolescents, UHR participants displayed
      decreased bilateral thalamus volume, which was associated with increased sleep
      dysfunction. CONCLUSIONS: Sleep dysfunction occurs during the pre-psychotic
      period, and may play a role in the etiology and pathophysiology of psychosis. In
      addition, the relationship of disrupted sleep to psychosis symptoms in UHR youth
      indicates that prevention and intervention strategies may be improved by
      targeting sleep stabilization in the pre-psychotic period.

PMID- 24094681
TI  - Lymphoscintigraphy in clinical routine practice: reproducibility and accuracy in
      melanoma patients with a long-term follow-up.
AB  - INTRODUCTION: The sentinel node status is the most important single factor
      determining overall survival for patients with localized melanoma. Preoperative
      lymphoscintigraphy (LS) is essential in locating the correct sentinel lymph node
      (SN) and the reproducibility of the method determines the accuracy of the
      sentinel node biopsy (SNB). This study aims at determining the reproducibility
      and accuracy of LS in routine clinical practice after long-term follow-up.
      PATIENTS AND METHODS: One hundred and eight melanoma patients with clinically
      unpredictable lymphatic drainage were prospectively enrolled to undergo two LS.
      The first LS was performed to determine the site and number of the lymphatic
      basins to plan SNB anesthesia and the second preoperative LS was to allow SN
      localization intra-operatively. RESULTS: Lymphatic drainage was demonstrated in
      all patients. In 84 of 108 cases, both LSs were concordant in terms of site and
      number of nodal basins visualized. After a median follow-up of 80 months, no
      nodal recurrence was observed in the five patients with a decreased number of
      lymph node basins. In the group with increased number of lymph node basins, one
      patient developed nodal metastases in the same regional lymph node basin
      visualized by both LS studies. CONCLUSION: LS is an accurate and reproducible
      method to determine the localization of the sentinel node in the day-to-day
      routine to clinical practice when primary melanoma is also located in body sites
      with variable lymphatic drainage.

PMID- 24094682
TI  - The caudal-lateral inserted transposition flap in reconstructive tumor surgery on
      the nasal ala.
AB  - The nasal region represents an important three-dimensional esthetic unit where
      minimal distortion will be obvious and disturbing. In this regard the
      reconstruction of the nasal ala in dermatologic tumor surgery may be challenging.
      We propose the reconstructive option of a caudal-lateral inserted transposition
      flap for this indication. The principle of this surgical alternative and the long
      term outcome is demonstrated in representative cases. The various indications and
      modifications of this reconstructive principle are discussed and compared to
      other remodeling alternatives. 

PMID- 24094683
TI  - Don't birth cohorts matter? A commentary and simulation exercise on Reither,
      Hauser, and Yang's (2009) age-period-cohort study of obesity.
AB  - Reither, Hauser, and Yang (2009) use a Hierarchical Age-Period-Cohort model (HAPC
      - Yang & Land, 2006) to assess changes in obesity in the USA population. Their
      results suggest that there is only a minimal effect of cohorts, and that it is
      periods which have driven the increase in obesity over time. We use simulations
      to show that this result may be incorrect. Using simulated data in which it is
      cohorts, rather than periods, that are responsible for the rise in obesity, we
      are able to replicate the period-trending results of Reither et al. In this
      instance, the HAPC model misses the true cohort trend entirely, erroneously finds
      a period trend, and underestimates the age trend. Reither et al.'s results may be
      correct, but because age, period and cohort are confounded there is no way to
      tell. This is typical of age-period-cohort models, and shows the importance of
      caution when any APC model is used. We finish with a discussion of ways forward
      for researchers wishing to model age, period and cohort in a robust and non
      arbitrary manner. 

PMID- 24094684
TI  - Young children understand and defend the entitlements of others.
AB  - Human social life is structured by social norms creating both obligations and
      entitlements. Recent research has found that young children enforce simple
      obligations against norm violators by protesting. It is not known, however,
      whether they understand entitlements in the sense that they will actively object
      to a second party attempting to interfere in something that a third party is
      entitled to do-what we call counter-protest. In two studies, we found that 3-year
      old children understand when a person is entitled to do something, and so they
      actively defend this person's entitlement against unjustified interference from
      second parties. In some cases, they even enforce second-order entitlements, for
      example, in the case of ownership where an owner is entitled to entitle others to
      use the owner's property. 

PMID- 24094685
TI  - Cow's Milk Allergy with Severe Eosinophilia.
AB  - Because the role of eosinophils in neonates is not well understood, the clinical
      significance of eosinophilia in neonates is unclear. We encountered a rare case
      of cow's milk allergy in a premature male infant with severe eosinophilia in the
      neonatal period. The peripheral blood eosinophil count in this infant was
      7,404/MUL at birth, and he produced stools with fresh blood immediately after
      birth and prior to the first feedings with regular cow's milk. Although the
      patient's eosinophil count normalized without specific treatment within 6 weeks
      after birth, it is possible that the causes of the eosinophilia in this infant
      prior to the first feedings with regular cow's milk were different from those
      after the first feedings. Cow's milk allergy was diagnosed on the basis of the
      patient's positivity for this allergy in the challenge test and subsequent
      allergen-specific lymphocyte stimulation test performed at 6 months of age. 

PMID- 24094686
TI  - A simple and inexpensive system for controlling body temperature in small animal
      experiments using MRI and the effect of body temperature on the hepatic kinetics
      of Gd-EOB-DTPA.
AB  - The purpose of this study was to develop a simple and inexpensive system for
      controlling body temperature in small animal experiments using magnetic resonance
      imaging (MRI) and to investigate the effect of body temperature on the kinetic
      behavior of gadolinium ethoxybenzyl diethylenetriamine pentaacetic acid (Gd-EOB
      DTPA) in the liver. In our temperature-control system, body temperature was
      controlled using a feedback-regulated heated or cooled air flow generated by two
      Futon dryers. The switches of the two Futon dryers were controlled using a
      digital temperature controller, in which the rectal temperature of a mouse
      measured by an optical fiber thermometer was used as the input. In experimental
      studies, male ICR mice aged 8weeks old were used and allocated into 5 groups (39
      , 36-, 33-, 30-, and 27-degree groups, n=10), in which the body temperature was
      maintained at 39  degrees C, 36  degrees C, 33  degrees C, 30  degrees C, and 27 
      degrees C, respectively, using our system. The dynamic contrast-enhanced MRI (DCE
      MRI) data were acquired with an MRI system for animal experiments equipped with a
      1.5-Tesla permanent magnet, for approximately 43min, after the injection of Gd
      EOB-DTPA into the tail vein. After correction of the image shift due to the
      temperature-dependent drift of the Larmor frequency using the gradient-based
      image registration method with robust estimation of displacement parameters, the
      kinetic behavior of Gd-EOB-DTPA was analyzed using an empirical mathematical
      model. With the use of this approach, the upper limit of the relative enhancement
      (A), the rates of contrast uptake (alpha) and washout (beta), the parameter
      related to the slope of early uptake (q), the area under the curve (AUC), the
      maximum relative enhancement (REmax), the time to REmax (Tmax), and the
      elimination half-life of the contrast agent (T1/2) were calculated. The body
      temperature of mice could be controlled well by use of our system. Although there
      were no significant differences in alpha, AUC, and q among groups, there were
      significant differences in A, REmax, beta, Tmax, and T1/2, indicating that body
      temperature significantly affects the kinetic behavior of Gd-EOB-DTPA in the
      liver. In conclusion, our system will be useful for controlling body temperature
      in small animal experiments using MRI. Because body temperature significantly
      affects the kinetic behavior of Gd-EOB-DTPA in the liver, the control of body
      temperature is essential and should be carefully considered when performing DCE
      MRI studies in small animal experiments. 

PMID- 24094687
TI  - Noncollinear wave mixing for measurement of dynamic processes in polymers:
      physical ageing in thermoplastics and epoxy cure.
AB  - Elastic wave mixing using an immersion method has shown effective monitoring and
      scanning capabilities when applied to thermoplastic ageing, epoxy curing, and non
      destructive testing. In water, excitation and reception of waves do not require
      physical contact between the tools and the specimen, making the acquisition of
      high-resolution C-scans possible. The nonlinear material parameters exhibit a
      much higher sensitivity to the specimen state compared to linear ones. Thus, the
      nonlinear data for polymethyl methacrylate (PMMA) have a 40% difference between
      zones of "young" and "aged" material, while the linear data show no difference at
      all. Methodology and logistics of the immersion wave-mixing method are discussed
      in detail. Monitoring of epoxy curing has also revealed a good sensitivity of the
      method to this complex process including several characteristic stages, such as
      the time of maximal viscosity, the gel time, and the vitrification time. These
      stages are independently verified in separate rheometry measurements. The
      presented method allows for a number of possibilities: wave-mode and frequency
      separations, elimination of surrounding medium influence, "steering" (scanning) a
      scattered wave, controlling the location of the intersection volume, single-sided
      or double-sided measurements, and operation in detector mode. 

PMID- 24094688
TI  - Investigation of the immune response to autologous, allogeneic, and xenogeneic
      mesenchymal stem cells after intra-articular injection in horses.
AB  - Mesenchymal stem cells have demonstrated immunomodulatory capabilities as well as
      modest efficacy in animal models of joint injury, warranting further study as a
      potential treatment of joint disease. The goal of the study was to investigate
      the blood and synovial immune and histologic response to intra-articular
      injection of autologous, allogeneic, and xenogeneic bone marrow-derived
      mesenchymal stem cells (MSC) in horses. The study group consisted of 6 five-year
      old Thoroughbred mares that had been injected previously with 15 million,
      genetically modified autologous, allogeneic, or xenogeneic MSC into the fetlock
      joints. One group of autologous cells was genetically modified to permit MSC
      biolocalization in the synovium. To assess response to the injection, synovial
      biopsies were obtained via arthroscopy 60 days after MSC injection for gross,
      histologic and molecular analyses. Peripheral blood mononuclear cells were
      isolated from each horse 120 days after MSC injection and co-cultured with a
      monolayer of each MSC group to permit quantification of activated CD4+
      lymphocytes and cytokine release (ELISA) upon re-exposure to MSC. Arthroscopic
      examination revealed normal synovium with no grossly detrimental effect to the
      synovium or cartilage. Intra-articular MSC produced a persistent mononuclear
      infiltrate for at least 60 days, mostly perivascular, identified as CD3+
      lymphocytes. An immune response (significant increase in CD4+ lymphocytes) was
      detected upon re-exposure to xenogeneic but not to allogeneic or autologous MSC.
      An inflammatory cytokine release from peripheral blood mononuclear cell/MSC co
      cultures was present in all MSC groups but was significantly greater in the
      xenogeneic group. In conclusion, intra-articular injection of MSC, regardless of
      cell origin, incited a persistent mononuclear synovitis demonstrating a sustained
      biologic influence of these cells. Allogeneic cells did not elicit a detectable
      immune response upon re-exposure using our methods. 

PMID- 24094689
TI  - Evaluation of immune functions in captive immature loggerhead sea turtles
      (Caretta caretta).
AB  - Sea turtles face numerous environmental challenges, such as exposure to chemical
      pollution and biotoxins, which may contribute to immune system impairment,
      resulting in increased disease susceptibility. Therefore, a more thorough
      assessment of the host's immune response and its susceptibility is needed for
      these threatened and endangered animals. In this study, the innate and acquired
      immune functions of sixty-five clinically healthy, immature, captive loggerhead
      sea turtles (Caretta caretta) were assayed using non-lethal blood sample
      collection. Functional immune assays were developed and/or optimized for this
      species, including mitogen-induced lymphocyte proliferation, natural killer (NK)
      cell activity, phagocytosis, and respiratory burst. Peripheral blood mononuclear
      cells (PBMC) and phagocytes were isolated by density gradient centrifugation on
      Ficoll-Paque and discontinuous Percoll gradients, respectively. The T lymphocyte
      mitogens ConA significantly induced lymphocyte proliferation at 1 and 2 MUg/mL
      while PHA significantly induced lymphocyte proliferation at 5 and 10 MUg/mL. The
      B lymphocyte mitogen LPS significantly induced proliferation at 1 MUg/mL.
      Monocytes demonstrated higher phagocytic activity than eosinophils. In addition,
      monocytes exhibited respiratory burst. Natural killer cell activity was higher
      against YAC-1 than K-562 target cells. These optimized assays may help to
      evaluate the integrity of loggerhead sea turtle's immune system upon exposure to
      environmental contaminants, as well as part of a comprehensive health assessment
      and monitoring program.

PMID- 24094690
TI  - Incorporation of constructivist assumptions into problem-based instruction: a
      literature review.
AB  - OBJECTIVES: The purpose of this literature review was to explore the use of
      distinct assumptions of constructivism when studying the impact of problem-based
      learning (PBL) on learners in undergraduate nursing programs. DESIGN: Content
      analysis research technique. DATA SOURCES: The literature review included
      information retrieved from sources selected via electronic databases, such as
      EBSCOhost, ProQuest, Sage Publications, SLACK Incorporation, Springhouse
      Corporation, and Digital Dissertations. REVIEW METHODS: The literature review was
      conducted utilizing key terms and phrases associated with problem-based learning
      in undergraduate nursing education. Out of the 100 reviewed abstracts, only 15
      studies met the inclusion criteria for the review. Four constructivist
      assumptions based the review process allowing for analysis and evaluation of the
      findings, followed by identification of issues and recommendations for the
      discipline and its research practice in the field of PBL. RESULTS: This
      literature review provided evidence that the nursing discipline is employing PBL
      in its programs, yet with limited data supporting conceptions of the
      constructivist perspective underlying this pedagogical approach. Three major
      issues were assessed and formed the basis for subsequent recommendations: (a)
      limited use of a theoretical framework and absence of constructivism in most of
      the studies, (b) incompatibility between research measures and research outcomes,
      and (c) brief exposure to PBL during which the change was measured. CONCLUSION:
      Educators have made the right choice in employing PBL as a pedagogical practice,
      yet the need to base implementation on constructivism is mandatory if the aim is
      a better preparation of graduates for practice. Undeniably there is limited
      convincing evidence regarding integration of constructivism in nursing education.
      Research that assesses the impact of PBL on learners' problem-solving and
      communication skills, self-direction, and motivation is paramount.

PMID- 24094691
TI  - Lesser-known myelin-related disorders: focal tumour-like demyelinating lesions.
AB  - INTRODUCTION: Focal tumour-like demyelinating lesions are defined as solitary
      demyelinating lesions with a diameter greater than 2 cm. In imaging studies,
      these lesions may mimic a neoplasm or brain abscess; as a result, invasive
      diagnostic and therapeutic measures may be performed that will in some cases
      increase morbidity. Our aim was to analyse and characterise these lesions
      according to their clinical, radiological, and pathological characteristics, and
      this data in addition to our literature review will contribute to a better
      understanding of these lesions. METHODS: This descriptive study includes 5 cases
      with pathological diagnoses. We provide subject characteristics gathered through
      reviewing their clinical, radiology, and pathology reports. RESULTS: Patients'
      ages ranged from 12 to 60 years; 3 patients were female. The time delay between
      symptom onset and hospital admission was 3 to 120 days. Clinical manifestations
      were diverse and dependent on the location of the lesion, pyramidal signs were
      found in 80% of patients, there were no clinical or radiological signs of spinal
      cord involvement, and follow-up times ranged from 1 to 15 years. CONCLUSION:
      Brain biopsy is the gold standard for the diagnosis of demyelinating tumour-like
      lesions; however, their clinical features, along with several magnetic resonance
      imaging features such as open ring enhancement, venular enhancement, the presence
      of glutamate in spectroscopy, and others, may be sufficient to differentiate
      neoplastic lesions from focal tumour-like demyelinating lesions.

PMID- 24094692
TI  - Catalytic activity of copper (II) oxide prepared via ultrasound assisted Fenton
      like reaction.
AB  - Copper (II) oxide nanoparticles were synthesized in an ultrasound assisted Fenton
      like aqueous reaction between copper (II) cations and hydrogen peroxide. The
      reactions were initiated with the degradation of hydrogen peroxide by ultrasound
      induced cavitations at 0  degrees C or 5  degrees C and subsequent generation of
      the OH radical. The radical was converted into hydroxide anion in Fenton-like
      reactions and copper hydroxides were readily converted to oxides without the need
      of post annealing or aging of the samples. The products were characterized with X
      ray diffraction (XRD), scanning electron microscopy (SEM), Fourier transform
      infrared spectroscopy (FTIR), and Brunauer-Emmett-Teller (BET) surface area
      analysis. Catalytic activity of the nanoparticles for the hydrogen peroxide
      assisted degradation of polycyclic aromatic hydrocarbons in the dark was tested
      by UV-visible spectroscopy with methylene blue as the model compound. The rate of
      the reaction was first order, however the rate constants changed after the
      initial hour. Initial rate constants as high as 0.030 min(-1) were associated
      with the high values of surface area, i.e. 70 m(2)/g. Annealing of the products
      at 150  degrees C under vacuum resulted in the decrease of the catalytic
      activity, underlying the significance of the cavitation induced surface defects
      in the catalytic process.

PMID- 24094693
TI  - Safety and tolerability of different titration rates of retigabine (ezogabine) in
      patients with partial-onset seizures.
AB  - Retigabine (RTG; international nonproprietary name)/ezogabine (EZG; US adopted
      name) is an antiepileptic drug (AED) that prolongs neuronal voltage-gated
      potassium-channel KCNQ2-5 (Kv 7.2-7.5) opening. This double-blind study evaluated
      different RTG/EZG dose-titration rates. Patients (N=73) with partial-onset
      seizures receiving concomitant AEDs were randomized to one of three titration
      groups, all of which were initiated at RTG/EZG 300mg/day divided into three equal
      doses. Fast-, medium-, and slow-titration groups received dose increments of
      150mg/day every 2, 4, and 7 days, respectively, achieving the target dose of
      1200mg/day after 13, 25, and 43 days, respectively. Safety assessments were
      performed throughout. Discontinuation rates due to treatment-emergent adverse
      events (TEAEs) were numerically higher in the fast- (10/23) and medium- (7/22)
      titration groups than in the slow-titration group (3/23) but statistical
      significance was achieved only for the high-titration group compared with the low
      titration group (p=0.024). Stratified analysis, with concomitant AEDs divided
      into enzyme inducers (carbamazepine, phenytoin, oxcarbazepine) or noninducers,
      showed that the risk of discontinuation due primarily to TEAEs was significantly
      higher in the fast- (p=0.010) but not in the medium-titration group (p=0.078)
      when compared with the slow-titration group. Overall, the slow-titration rate
      appeared to be best tolerated and was used in further efficacy and safety studies
      with RTG/EZG. 

PMID- 24094694
TI  - A blueprint of pain curriculum across prelicensure health sciences programs: one
      NIH Pain Consortium Center of Excellence in Pain Education (CoEPE) experience.
AB  - To improve U.S. pain education and promote interinstitutional and
      interprofessional collaborations, the National Institutes of Health Pain
      Consortium has funded 12 sites to develop Centers of Excellence in Pain Education
      (CoEPEs). Each site was given the tasks of development, evaluation, integration,
      and promotion of pain management curriculum resources, including case studies
      that will be shared nationally. Collaborations among schools of medicine,
      dentistry, nursing, pharmacy, and others were encouraged. The John D. Loeser
      CoEPE is unique in that it represents extensive regionalization of health science
      education, in this case in the region covering the states of Washington, Wyoming,
      Alaska, Montana, and Idaho. This paper describes a blueprint of pain content and
      teaching methods across the University of Washington's 6 health sciences schools
      and provides recommendations for improvement in pain education at the
      prelicensure level. The Schools of Dentistry and Physician Assistant provide the
      highest percentage of total required curriculum hours devoted to pain compared
      with the Schools of Medicine, Nursing, Pharmacy, and Social Work. The findings
      confirm the paucity of pain content in health sciences curricula, missing
      International Association for the Study of Pain curriculum topics, and limited
      use of innovative teaching methods such as problem-based and team-based learning.
      PERSPECTIVE: Findings confirm the paucity of pain education across the health
      sciences curriculum in a CoEPE that serves a large region in the United States.
      The data provide a pain curriculum blueprint that can be used to recommend added
      pain content in health sciences programs across the country.

PMID- 24094698
TI  - Association between growth hormone receptor AluI polymorphism and fertility of
      Holstein cows.
AB  - The aim of this work was to determine the effects of a growth hormone receptor
      (GHR) AluI polymorphism on the reproductive performance of Holstein cows. The
      cows (n = 94) were on the study from 3 weeks prepartum until 210 days in milk
      (DIM). Blood samples were collected at -21, 0, 7, 21, and 60 DIM. For GHR
      genotyping, DNA was extracted from blood and the presence of the alleles
      determined after polymerase chain reaction and digestion with the restriction
      enzyme AluI. Milk samples were collected for progesterone analysis and detection
      of ovulation until first breeding. Cows were submitted to an OvSynch-TAI protocol
      at 55 DIM that was repeated for cows diagnosed as not pregnant. Data were
      analyzed with SAS for polynomial effects of the presence of 0, 1, or 2 GHR AluI (
      ) alleles. Among the cows, 37% had the AluI(+/+) genotype, 51% had AluI(-/+), and
      12% were AluI(-/-). Interval from calving to first ovulation was not different
      among genotypes (P > 0.05). Cows carrying at least one GHR AluI(-) allele had
      fewer number of services per conception (P = 0.02). In addition, there was a
      linear reduction (P = 0.02) in the calving to conception interval among genotypes
      with fewest days for GHR AluI(-/-) cows. GHR AluI(-/-) cows also had the highest
      serum IGF-I concentrations (P = 0.03). Milk production and composition were not
      different among genotypes (P > 0.05). The presence of one or two GHR AluI(-)
      alleles in Holstein cows was associated with a linear reduction in the calving to
      conception interval and a reduction in the number of AI/conception. 

PMID- 24094695
TI  - Gabapentin alleviates facet-mediated pain in the rat through reduced neuronal
      hyperexcitability and astrocytic activation in the spinal cord.
AB  - Although joint pain is common, its mechanisms remain undefined, with little known
      about the spinal neuronal responses that contribute to this type of pain.
      Afferent activity and sustained spinal neuronal hyperexcitability correlate to
      facet joint loading and the extent of behavioral sensitivity induced after
      painful facet injury, suggesting that spinal neuronal plasticity is induced in
      association with facet-mediated pain. This study used a rat model of painful C6
      C7 facet joint stretch, together with intrathecal administration of gabapentin,
      to investigate the effects of one aspect of spinal neuronal function on joint
      pain. Gabapentin or saline vehicle was given via lumbar puncture prior to and at
      1 day after painful joint distraction. Mechanical hyperalgesia was measured in
      the forepaw for 7 days. Extracellular recordings of neuronal activity and
      astrocytic and microglial activation in the cervical spinal cord were evaluated
      at day 7. Gabapentin significantly (P = .0001) attenuated mechanical
      hyperalgesia, and the frequency of evoked neuronal firing also significantly
      decreased (P < .047) with gabapentin treatment. Gabapentin also decreased (P <
      .04) spinal glial fibrillary acidic protein expression. Although spinal Iba1
      expression was doubled over sham, gabapentin did not reduce it. Facet joint
      mediated pain appears to be sustained through spinal neuronal modifications that
      are also associated with astrocytic activation. PERSPECTIVE: Intrathecal
      gabapentin treatment was used to investigate behavioral, neuronal, and glial
      response in a rat model of painful C6-C7 facet joint stretch. Gabapentin
      attenuated mechanical hyperalgesia, reduced evoked neuronal firing, and decreased
      spinal astrocytic activation. This study supports that facet joint pain is
      sustained through spinal neuronal and astrocytic activation.

PMID- 24094700
TI  - Quantification of taurine in energy drinks using 1H NMR.
AB  - The consumption of so called energy drinks is increasing, especially among
      adolescents. These beverages commonly contain considerable amounts of the amino
      sulfonic acid taurine, which is related to a magnitude of various physiological
      effects. The customary method to control the legal limit of taurine in energy
      drinks is LC-UV/vis with postcolumn derivatization using ninhydrin. In this paper
      we describe the quantification of taurine in energy drinks by (1)H NMR as an
      alternative to existing methods of quantification. Variation of pH values
      revealed the separation of a distinct taurine signal in (1)H NMR spectra, which
      was applied for integration and quantification. Quantification was performed
      using external calibration (R(2)>0.9999; linearity verified by Mandel's fitting
      test with a 95% confidence level) and PULCON. Taurine concentrations in 20
      different energy drinks were analyzed by both using (1)H NMR and LC-UV/vis. The
      deviation between (1)H NMR and LC-UV/vis results was always below the expanded
      measurement uncertainty of 12.2% for the LC-UV/vis method (95% confidence level)
      and at worst 10.4%. Due to the high accordance to LC-UV/vis data and adequate
      recovery rates (ranging between 97.1% and 108.2%), (1)H NMR measurement presents
      a suitable method to quantify taurine in energy drinks.

PMID- 24094701
TI  - [Adult-onset Still's disease as a manifestation of malignancy: report of a
      patient with melanoma and literature review].
AB  - INTRODUCTION: A malignancy must be carefully excluded before ruling in the
      diagnosis of adult onset Still's disease (AOSD). However, an occult or poorly
      symptomatic malignancy can easily be overlooked. CASE REPORT: We report a 50-year
      old female patient who presented with features of adult onset Still's disease
      (AOSD), in fact heralding a malignant melanoma with fatal outcome since
      discovered lately, at a metastatic stage. In retrospect, the only significant
      atypical feature was cholestatic hepatitis, which soon disappeared upon
      institution of glucocorticoid treatment. The literature review identified 27
      additional cases of AOSD-like disease associated with malignancy published since
      1980 including solid cancer in 61% of the cases (especially breast and lung) and
      haematological malignancies in 39% of the cases (especially malignant lymphoma).
      The interval between OASD-like symptoms and malignancy averaged 8 months, and
      AOSD most often preceding malignancy. Although idiopathic AOSD and neoplastic
      AOSD-like disease are often indistinguishable initially, some features could
      point toward the latter: an onset of AOSD after the age of 40 years, the presence
      of atypical clinical, biological, or immunological features in less than one
      third of the cases, and a poor response to NAIDS or systemic glucocorticoids in
      61% of the cases. CONCLUSION: Making the differential diagnosis of malignancy
      associated AOSD in a timely fashion remains a primary goal, even in the most
      typical cases and those showing good initial therapeutic response.

PMID- 24094702
TI  - Is the Life Space Assessment applicable to a palliative care population? Its
      relationship to measures of performance and quality of life.
AB  - CONTEXT: The spatial environments that palliative care patients frequent for
      business and leisure constrict as their disease progresses and their physical
      functioning deteriorates. Measuring a person's movement within his or her own
      environment is a clinically relevant and patient-centered outcome because it
      measures function in a way that reflects actual and not theoretical
      participation. OBJECTIVES: This exploratory study set out to test whether the
      Life-Space Assessment (LSA) would correlate with other commonly used palliative
      care outcome measures of function and quality of life. METHODS: The baseline LSA,
      Australia-modified Karnofsky Performance Status Scale (AKPS), and the European
      Organization for Research and Treatment of Cancer Quality of Life Questionnaire
      Core 15-Palliative (EORTC QLQ-C15-PAL) scores from two large clinical trials were
      used to calculate correlation coefficients between the measures. Convergent
      validity analysis was undertaken by comparing LSA scores between participants
      with higher (>=70) and lower (<=60) AKPS scores. RESULTS: The LSA was correlated
      significantly and positively with the AKPS, with a moderate correlation
      coefficient of 0.54 (P<0.001). There was a significant weak negative correlation
      between the LSA and the EORTC QLQ-C15-PAL, with a small coefficient of -0.22
      (P=0.027), but a strong correlation between the LSA and the EORTC QLQ-C15-PAL
      item related to independent activities of daily living (r=-0.654, P<0.01). A
      significant difference in the LSA score between participants with higher (>=70)
      and lower (<=60) AKPS scores t(97)=-4.35, P<0.001) was found. CONCLUSION: The LSA
      appears applicable to palliative care populations given the convergent validity
      and capacity of this instrument to differentiate a person's ability to move
      through life-space zones by performance status. Further research is required to
      validate and apply the LSA within community palliative care populations.

PMID- 24094703
TI  - Preparedness planning before mechanical circulatory support: a "how-to" guide for
      palliative medicine clinicians.
AB  - The role of palliative medicine in the care of patients with advanced heart
      failure, including those who receive mechanical circulatory support, has grown
      dramatically in the last decade. Previous literature has suggested that
      palliative medicine providers are well poised to assist cardiologists,
      cardiothoracic surgeons, and the multidisciplinary cardiovascular team with
      promotion of informed consent and initial and iterative discussions regarding
      goals of care. Although preparedness planning has been described previously, the
      actual methods that can be used to complete a preparedness plan have not been
      well defined. Herein, we outline several key aspects of this approach and detail
      strategies for engaging patients who are receiving mechanical circulatory support
      in preparedness planning. 

PMID- 24094704
TI  - Levodopa treatment in Parkinson's disease: how does it affect dysphagia
      management?

PMID- 24094705
TI  - Response to 'Re: Paediatric percutaneous nephrolithotomy: Single-centre 10-year
      experience. J Pediatr Urol. 2013 Aug; 9(4):472-5'.

PMID- 24094706
TI  - Letter from the editors: nononcologic PET imaging.

PMID- 24094707
TI  - FDG PET imaging in sarcoidosis.
AB  - The objective of this review is to highlight the clinical utility of FDG-PET/CT
      for evaluation of patients with chronic sarcoidosis. The emphasis was on the
      potential advantages and disadvantages of this technique in these patients based
      on which recommendations were made. The advantage of FDG-PET/CT technique is that
      it can visualize FDG accumulation in activated inflammatory cells and
      simultaneously provide PET and CT images. Of particular interest is the use of
      FDG-PET/CT for the staging and identification of occult sites and sites suitable
      for biopsy and for the assessment of inflammatory active sarcoidosis in patients
      with prolonged symptoms, especially when other markers of the disease are within
      normal values. FDG-PET/CT also provides a better visualization of extrathoracic
      sites of active sarcoidosis, such as in the bones, liver, spleen, and
      retroperitoneal lymph nodes. The use of FDG-PET/CT is of special interest in
      cardiac sarcoidosis because this potentially life-threatening disease is
      sometimes present in asymptomatic patients. FDG-PET/CT also has a role in the
      clinical management of patients with chronic persistent sarcoidosis, such as for
      planning treatment, monitoring response, and long-term follow-up. The limitations
      of FDG-PET/CT in patients with sarcoidosis are discussed in the context of a
      "sarcoidosis-lymphoma syndrome" and potentially excessive radiation exposure.
      Further prospective multicentre studies are needed to refine the clinical
      applications of FDG-PET/CT in patients with sarcoidosis and drive the field
      forward. 

PMID- 24094708
TI  - FDG PET imaging in cystic fibrosis.
AB  - Cystic fibrosis (CF) is characterized by persistent neutrophilic lung
      inflammation that begins early in life and leads to an inexorable progressive
      loss of lung function over time, causing significant morbidity and mortality.
      Studies to date support the hypothesis that higher levels of lung inflammation
      lead to worsening lung dysfunction. However, measuring the extent and severity of
      lung inflammation in the CF lung is difficult as few lung-specific biomarkers of
      inflammation can quantify the regional and whole-lung inflammatory burden
      accurately and reproducibly. PET with (18)F-fluorodeoxyglucose ((18)F-FDG) has
      shown promise in measuring lung inflammation in both acute and chronic lung
      diseases. Several studies have now shown that (18)F-FDG uptake may be a useful
      measure of lung inflammation in CF. The whole-lung rate of (18)F-FDG uptake in
      stable CF, quantified by the Patlak graphical analysis, appears to correlate with
      more rapidly declining lung function. Acute exacerbation, on the contrary, leads
      to focally increased (18)F-FDG uptake, which decreases with antibiotic treatment.
      These small studies are the first attempts to characterize the patterns of (18)F
      FDG uptake in CF and suggest a potential role for (18)F-FDG as a treatment
      modifiable biomarker of lung inflammation in CF. 

PMID- 24094709
TI  - PET/CT imaging of inflammatory bowel disease.
AB  - PET/CT imaging has become an important part of the evaluation of patients with
      many types of cancer. This imaging modality can also be used to image areas of
      active inflammation, such as those occurring in patients with active inflammatory
      bowel disease (IBD) (Crohn's disease and ulcerative colitis). The standard
      methods of determining a patient's disease activity are either indirect, such as
      blood and stool tests, or invasive, such as colonoscopy. FDG-PET imaging is a
      noninvasive, direct method of evaluating bowel inflammation and represents a
      significant advancement in the care of these patients. The PET/CT technique is
      very similar to that used for oncology imaging. Minor changes can be instituted
      to improve the accuracy, as well as to reduce the radiation exposure to the
      patient. This paper reviews the literature on the use of FDG-PET imaging in IBD
      in both the adult and pediatric populations. Future improvements in the technique
      should focus on decreasing the radiation dose to the patient and on decreasing
      the cost of the examination. The FDG-PET/CT technique is an excellent method for
      the noninvasive quantification of bowel inflammation in patients with IBD. 

PMID- 24094710
TI  - Musculoskeletal imaging using fluoride PET.
AB  - The convenience of (18)F-fluoride imaging is undeniable both because of its
      favorable tracer and because of its technical characteristics, including high
      image quality and short examination times leading to increased patient comfort.
      Depending on the activity administered, the radiation dose to patients is about
      comparable to higher using (18)F-fluoride for bone imaging compared with
      conventional scintigraphy using 99mTc-methylene diphosphonate. In times of
      molybdenum shortage, (18)F-fluoride represents a good alternative to 99mTc-based
      bone tracers. Besides malignant skeletal disease(18)F-fluoride PET/CT has in the
      last decade been investigated in a variety of non-oncologic musculoskeletal
      disorders of all parts of the skeleton. Studies included imaging of the skull
      with a special focus on bisphosphonate-induced osteonecrosis of the jaw in
      patients treated with bisphosphonates due to benign or malignant bone changes.
      Further studies evaluated the appendicular skeleton with emphasis on postsurgical
      changes including patients after knee and hip surgery and patients having
      received bone grafts of their limbs. Also, therapeutic effect of (18)F-fluoride
      PET/CT on patients with unclear foot pain was investigated. Finally imaging of
      the axial skeleton was analyzed including patients with ankylosing spondylitis
      and with Paget disease as well as patients after spine surgery including
      assessment of cage incorporation after cervical and lumbar spine fusion surgery.
      Furthermore, children suspected of child abuse as well as young patients with
      back pain were investigated by either (18)F-fluoride PET or PET/CT. Regarding its
      favorable technical aspects as well as study results presented, it is imaginable
      that (18)F-fluoride PET/(CT) will be increasingly used for non-oncologic
      musculoskeletal imaging in the future either as an adjunct or alternative to so
      far established imaging modalities and seems to be promising regarding decision
      making in the therapeutic management of patients with non-oncologic
      musculoskeletal disorders.

PMID- 24094711
TI  - Cardiac PET: metabolic and functional imaging of the myocardium.
AB  - Cardiac PET has evolved over the past 30 years to gain wider acceptance as a
      valuable modality for a variety of cardiac conditions. Wider availability of
      scanners as well as changes in reimbursement policies in more recent years has
      further increased its use. Moreover, with the emergence of novel radionuclides as
      well as further advances in scanner technology, the use of cardiac PET can be
      expected to increase further in both clinical practice and the research arena.
      PET has demonstrated superior diagnostic accuracy for the diagnosis of coronary
      artery disease in comparison with single-photon emission tomography while it
      provides robust prognostic value. The addition of absolute flow quantification
      increases sensitivity for 3-vessel disease as well as providing incremental
      functional and prognostic information. Metabolic imaging using (18)F
      fluorodeoxyglucose can be used to guide revascularization in the setting of heart
      failure and also to detect active inflammation in conditions such as cardiac
      sarcoidosis and within atherosclerotic plaque, improving our understanding of the
      processes that underlie these conditions. However, although the pace of new
      developments is rapid, there remains a gap in evidence for many of these advances
      and further studies are required. 

PMID- 24094712
TI  - An overview of PET neuroimaging.
AB  - Over the past 35 years or so, PET brain imaging has allowed powerful and unique
      insights into brain function under normal conditions and in disease states.
      Initially, as PET instrumentation continued to develop, studies were focused on
      brain perfusion and glucose metabolism. This permitted refinement of brain
      imaging for important, non-oncologic clinical indications. The ability of PET to
      not only provide spatial localization of metabolic changes but also to accurately
      and consistently quantify their distribution proved valuable for applications in
      the clinical setting. Specifically, glucose metabolism brain imaging using (F-18)
      fluorodeoxyglucose continues to be invaluable for evaluating patients with
      intractable seizures for identifying seizure foci and operative planning.
      Cerebral glucose metabolism also contributes to diagnosis of neurodegenerative
      diseases that cause dementia. Alzheimer disease, dementia with Lewy bodies, and
      the several variants of frontotemporal lobar degeneration have differing typical
      patterns of hypometabolism. In Alzheimer disease, hypometabolism has furthermore
      been associated with poorer cognitive performance and ensuing cognitive and
      functional decline. As the field of radiochemistry evolved, novel radioligands
      including radiolabeled flumazenil, dopamine transporter ligands, nicotine
      receptor ligands, and others have allowed for further understanding of molecular
      changes in the brain associated with various diseases. Recently, PET brain
      imaging reached another milestone with the approval of (F-18) florbetapir imaging
      by the United States Federal Drug Administration for detection of amyloid plaque
      accumulation in brain, the major histopathologic hallmark of Alzheimer disease,
      and efforts have been made to define the clinical role of this imaging agent in
      the setting of the currently limited treatment options. Hopefully, this
      represents the first of many new radiopharmaceuticals that would allow improved
      diagnostic and prognostic information in these and other clinical applications,
      including Parkinson disease and traumatic brain injury.

PMID- 24094714
TI  - Use of vertebroplasty to prevent proximal junctional fractures in adult deformity
      surgery: a biomechanical cadaveric study.
AB  - BACKGROUND CONTEXT: Vertebral compression fractures at the proximal junction are
      common complications of long spinal fusion surgeries that can contribute to the
      development of proximal junctional kyphosis or proximal junctional failure. To
      our knowledge, no biomechanical studies have addressed the effect of vertebral
      augmentation at the proximal junction. PURPOSE: To evaluate the effectiveness of
      prophylactic vertebroplasty in reducing the incidence of vertebral compression
      fractures at the proximal junction after a long spinal fusion in a cadaveric
      spine model. STUDY DESIGN: Biomechanical cadaveric study. METHODS: We divided 18
      cadaveric spine specimens into three groups of six spines each: a control group,
      a group treated with one-level prophylactic vertebroplasty at the upper
      instrumented vertebra, and a group treated with two-level prophylactic
      vertebroplasty at the upper instrumented vertebra and the supra-adjacent
      vertebra. In all spines, the pedicles were instrumented from L5 to T10. Using
      eccentric axial loading, the specimens were then compressed until failure.
      Failure was defined as a precipitous decrease in load with increasing
      compression. The effect of augmentation on load-to-failure was checked using
      linear regression. The effect of augmentation on incidence of adjacent fractures
      was checked using logistic regression. Differences at the level of p<.05 were
      considered significant. KyphX cement introducer was donated by Kyphon, and the
      pedicle screws were donated by DePuy. RESULTS: Fractures occurred in 12 of 18
      specimens: five in the control group, six in the one-level group, and only one in
      the two-level group; these differences were statistically significant.
      CONCLUSIONS: Prophylactic vertebroplasty at the upper instrumented level and its
      supra-adjacent vertebra reduced the incidence of junctional fractures after long
      posterior spinal instrumentation in this axially loaded cadaveric model.
      Additional studies are necessary to determine if these results are translatable
      to clinical practice.

PMID- 24094713
TI  - Current and future trends in the anatomical and functional imaging of head and
      neck paragangliomas.
AB  - Head and neck paragangliomas (HNPGLs) account for approximately 3% of all
      paragangliomas (PGLs). Most often, HNPGLs are benign, nonsecreting, and slowly
      progressing. The initial physical examination and biochemical diagnosis usually
      adds very little to the proper diagnosis of these tumors, and, therefore,
      radiologists and nuclear medicine physicians play a pivotal role in providing the
      initial diagnosis, the locoregional staging, and the plan for detecting potential
      multicentric or metastatic lesions. Based on several current studies, the most
      accurate use of HNPGL-specific initial and subsequent imaging modalities must be
      guided by the knowledge of genetics and the specifically measured biochemical
      profile of these tumors for the proper management of these patients. Thus, this
      short review article presents the application of the most up-to-date anatomical
      and functional imaging approaches to HNPGLs tightly linked to the clinical
      management of these patients. Based on the most recent studies, 18F-FDOPA PET/CT
      has been shown to be a useful addition to anatomical imaging in the preoperative
      localization and molecular assessment of HNPGLs. It is estimated that the
      frequency of metabolically active PGLs on 18F-FDOPA PET/CT in this region is
      higher than 90%. For patients with hereditary PGL syndromes, (18)F-FDG-PET/CT
      should be reserved. Imaging of somatostatin receptors using Octreoscan or 68Ga
      labeled somatostatin analogues plays an important role for selecting patients for
      targeted radiation therapy. This review also concludes that it is expected that
      in the near future, these patients will indeed benefit from new diagnostic
      approaches based on the identification of new targets by molecular profiling
      studies that will result in the development of novel PGL-specific
      radiopharmaceuticals.

PMID- 24094715
TI  - Evaluation of pelvic morphology in the sagittal plane.
AB  - BACKGROUND CONTEXT: It is generally accepted that for normal subjects the angle
      of pelvic incidence (PI) increases during childhood and then remains unchanged
      throughout adolescence and adulthood. However, recent findings show that PI
      increases linearly throughout the lifespan due to morphological changes of the
      pelvis. PURPOSE: A retrospective study aiming to determine the extent of
      morphological changes of the pelvis related to the age of the subjects. STUDY
      DESIGN: Pelvic morphology was evaluated in a normal adult population by measuring
      the anatomical parameters of sagittal pelvic alignment. PATIENT SAMPLE: The final
      study cohort consisted of 330 subjects (mean age, 45.3 years; standard deviation,
      18.1 years; range, 18-87 years; 164 male and 166 female subjects). OUTCOME
      MEASURES: Physiologic measures, obtained as measurements of PI, sacral end plate
      width (S1W), and pelvic thickness (PTH). METHODS: Parameters of PI, S1W, and PTH
      were evaluated from computed tomography images of the subjects. The measured PTH
      was normalized according to S1W and age of the subjects, allowing the comparison
      among anatomies of different sizes. The normalized components of PTH in
      anteroposterior and cephalocaudal directions were computed to determine the
      configuration and extent of changes in pelvic morphology related to subject age.
      RESULTS: Statistically significant correlation with both age and PI was obtained
      for all normalized parameters (except for the anteroposterior component of PTH
      for male subjects), and no statistically significant differences were observed
      between the sexes. With increasing PI that occurs due to the aging process, a
      decrease of PTH can be observed that is manifested not only as an increase of the
      distance between the sacrum and the hip axis in the anterior direction but
      considerably more as a decrease of the distance between the sacrum and the hip
      axis in the cephalic direction. By considering these morphological changes in the
      pelvis simultaneously, the hip axis can move only within a narrow area.
      CONCLUSIONS: The changes in pelvic morphology due to the aging process occur in
      the anterior direction, which may be due to the remodeling process affecting the
      coxal bone that results in an anterior drift of the acetabulum relative to the
      sacrum. More importantly, the changes are considerably more evident in the
      cephalic direction, which may be the result of the weight-bearing loads and
      consequent wear of acetabular cartilage.

PMID- 24094716
TI  - Large completely calcified spinal meningioma.

PMID- 24094718
TI  - Testing agreement between a new method and the gold standard-how do we test?
AB  - Data analysis can be the most challenging aspect of a research study. Having been
      taught statistical techniques that tend to be based on finding significant
      differences or significant relationships, difficulties arise when trying to
      determine if a newly developed method is equally as good as the established
      method (the gold standard). Testing for significant differences is rigorous and
      it would be rare for researchers to report significant differences without using
      an appropriate statistical test. Testing for agreement is assessed with far less
      rigour. Analysis of papers in this journal suggests that testing for agreement is
      an area that could be improved by a better understanding of statistical methods
      by biomechanics researchers. This perspectives paper focusses on informing the
      reader about the assessment of agreement between two methods. 

PMID- 24094717
TI  - Minimally invasive compared with open lumbar laminotomy: no functional benefits
      at 6 or 24 months after surgery.
AB  - BACKGROUND CONTEXT: Comparative studies between open and minimally invasive
      surgical (MIS) approaches for the treatment of spinal stenosis have mainly
      investigated immediate postoperative parameters. PURPOSE: We aimed to compare the
      postoperative improvements in functional and pain scores between open versus MIS
      lumbar laminotomy and to describe the complications of each method. STUDY
      DESIGN/SETTING: We conducted as retrospective review of prospectively collected
      data. PATIENT SAMPLE: We included 113 patients. OUTCOME MEASURES: Visual analog
      scale for back and leg pain, Oswestry Disability Index (ODI), the North American
      Spine Society score on neurogenic symptoms (NS), and average Short Form Health
      Survey-36 (SF-36) score. Accidental durotomies and patients with reoperations are
      presented. METHODS: We obtained a list of patients who underwent either MIS or
      open unilateral one-level lumbar laminotomy for the treatment of neural foraminal
      or lateral recess stenosis with unilateral leg NS. Outcome measures are presented
      at 6 and 24 months postoperatively. RESULTS: From 2000 to 2008, 113 patients (30
      open, 83 MIS) underwent a one-level lumbar laminotomy and had complete
      postoperative data available for analysis. Between the approaches, there were no
      differences in baseline demographic data or functional scores. At 6 and 24 months
      after surgery, there were no differences in improvement in back or leg pain, or
      improvement in ODI, NS, or SF-36 scores. The MIS group reported greater
      satisfaction with treatment at 6 months (p=.009) but not at 24 months. Within the
      MIS group, three patients (3.6%) experienced an inadvertent durotomy and two
      patients (2.4%) underwent fusion of the operated segment within 24 months.
      CONCLUSIONS: Compared with an open approach, MIS lumbar laminotomy gave no clear
      advantages in longer term functional or pain scores. The MIS group also had
      patients with inadvertent durotomies and reoperation within 2 years. In any
      lumbar decompressive surgery, the purported advantages of an MIS approach should
      be carefully weighed against potential complications. For a relatively simple
      surgery such as laminotomy, the open approach remains a safe and straightforward
      option.

PMID- 24094719
TI  - Management of exsanguination during laser lead extraction.

PMID- 24094720
TI  - Case 6-2013: Perioperative management of an adult patient with tetralogy of
      fallot and pheochromocytoma.

PMID- 24094721
TI  - Evaluation and management of pediatric near-hanging injury.
AB  - INTRODUCTION: Children surviving a strangulation event are unique from adults in
      that they are at risk for significant airway compromise due to the smaller
      relative size of their airways. To date, no study has specifically evaluated the
      laryngeal findings and management of pediatric near-hanging patients. METHODS: A
      retrospective chart review was performed on all near-hangings presenting to the a
      tertiary care children's hospital from January 2001 until June 2010. Demographic
      information was compiled in addition to laryngeal findings. RESULTS: Sixteen
      children were identified. Four had a documented laryngeal injury, one of which
      was a major injury requiring a tracheotomy. CONCLUSION: Laryngeal examination
      should be standard of care for any child presenting after a near-hanging event.

PMID- 24094722
TI  - C-type lectin receptors mRNA expression in patients with otitis media with
      effusion.
AB  - OBJECTIVE: The role of C-type lectin receptor, a type of pattern recognition
      receptor, in otitis media with effusion (OME) is unclear. We assayed the levels
      of expression of C-type lectin receptor mRNA in children with OME and evaluated
      its relationship to the presence of bacteria, accompanying diseases, and
      characteristics of exudates. SUBJECTS AND METHODS: The study population consisted
      of 73 children with OME who had undergone ventilating tube insertion. The levels
      of expression of Dectin-1, MR1, MR2, DC-SIGN, Syk, Card-9, Bcl-10, Malt-1, Src,
      Dec-205, Galectin-1, Tim-3, Trem-1, and DAP-12 mRNA in middle ear effusion were
      determined by real-time PCR. The level of expression of each mRNA was correlated
      with the presence of bacteria, accompanying diseases, and exudates
      characteristics. RESULTS: The levels of expression of C-type lectin receptor
      mRNAs were not associated with bacterial presence or exudates characteristics
      (p>0.05 each). Levels of expression, however, were significantly higher in
      patients with sinusitis, adenoid vegetation or adenoiditis, and allergic rhinitis
      (p<0.05 each). CONCLUSIONS: Levels of expression of C-type lectin receptor mRNA
      may be associated with the pathogenesis of OME, being significantly higher in
      patients with than without accompanying sinusitis, adenoid vegetation or
      adenoiditis, and allergic rhinitis.

PMID- 24094723
TI  - Medication and suicide risk in schizophrenia: a nested case-control study.
AB  - INTRODUCTION: Patients with schizophrenia are at increased risk of suicide, but
      data from controlled studies of pharmacotherapy in relation to suicide risk is
      limited. AIM: To explore suicide risk in schizophrenia in relation to medication
      with antipsychotics, antidepressants, and lithium. METHODS: Of all patients with
      a first clinical discharge diagnosis of schizophrenia or schizoaffective disorder
      in Stockholm County between 1984 and 2000 (n=4000), patients who died by suicide
      within five years from diagnosis were defined as cases (n=84; 54% male).
      Individually matched controls were identified from the same population.
      Information on prescribed medication was retrieved from psychiatric records in a
      blinded way. Adjusted odds ratios [OR] of the association between medication and
      suicide were calculated by conditional logistic regression. RESULTS: Lower
      suicide risk was found in patients who had been prescribed a second generation
      antipsychotic (clozapine, olanzapine, risperidone, or ziprasidone; 12 cases and
      20 controls): OR 0.29 (95% confidence interval [CI], 0.09-0.97). When the 6 cases
      and 8 controls who had been prescribed clozapine were excluded, the OR was 0.23
      (95% CI 0.06-0.89). No significant association was observed between suicide and
      prescription of any antipsychotic, depot injection antipsychotics,
      antidepressants, SSRI, or lithium. CONCLUSIONS: Lower suicide risk for patients
      who had been prescribed second generation antipsychotics may be related to a
      pharmacological effect of these drugs, to differences in adherence, or to
      differences in other patient characteristics associated with lower suicide risk.

PMID- 24094725
TI  - Genetic defects in Indian Wilson disease patients and genotype-phenotype
      correlation.
AB  - Wilson disease (WD) is caused by defects in ATP7B gene due to impairment of
      normal function of the copper transporting P-type ATPase. This study describes a
      comprehensive genetic analysis of 199 Indian WD patients including mutations
      detected in our previous studies, undertakes functional assessment of the
      nucleotide variants in ATP7B promoter and correlates genotype with disease
      phenotype. The patient cohort harbors a total of 10 common and 48 rare mutations
      in the coding region of ATP7B including 21 novel changes. The common mutations
      represent 74% of characterized coding mutant alleles with p.C271X (63/260) and
      p.G1101R (7/31) being the most prevalent in eastern and western Indian patients,
      respectively. The mutation spectrum between east and west is mostly different
      with only three mutations (p.G1061E, p.N1270S and p.A1049A-fs) being shared
      between both the groups. Eight novel and 10 reported variants have been detected
      in the promoter and non-coding regions (5' and 3'UTRs) of ATP7B. Promoter
      reporter assay demonstrated that 3 novel variants and 5 reported polymorphisms
      alter the gene expression to a considerable extent; hence might play important
      role in ATP7B gene regulation. We devised the neurological involvement score to
      capture the spectrum of neurological involvement in WD patients. By utilizing the
      age at onset, neurological involvement score and ATP7B mutation background, we
      generated a genotype-phenotype matrix that could be effectively used to depict
      the phenotypic spectra of WD affected individuals and serve as a platform to
      identify prospective "outliers" to be investigated for their remarkable
      phenotypic divergence.

PMID- 24094724
TI  - Rare variants in ANO3 are not a susceptibility factor in essential tremor.

PMID- 24094726
TI  - Paraduodenal pancreatitis.
AB  - Paraduodenal pancreatitis is a distinct clinicopathological entity involving the
      duodenum and the pancreatic tissue in the vicinity of the minor papilla. Most
      afflicted patients are young alcoholic males who present clinically with upper
      abdominal pain, weight loss, nausea, and vomiting. Pancreatic tissue elements in
      the duodenal wall and impedance to exocrine pancreatic secretions at the minor
      papilla are key factors in the pathogenesis of this condition. On imaging, the
      condition may manifest as a solid fibrotic mass around the minor papilla or as
      cysts in the duodenum and the pancreaticoduodenal groove. Duodenal stenosis,
      biliary strictures, chronic calcifying pancreatitis, and pancreatic ductal
      dilatation are also often observed. 

PMID- 24094727
TI  - Spirituality aspects in patients with epilepsy.
AB  - PURPOSE: Do epilepsy and spirituality interact? This study aimed to determine
      whether an easy-to-administer scale, such as the spirituality self-rating scale
      (SSRS), could detect increased religiousness in people with epilepsy and verify
      how epilepsy influences spirituality. METHODS: A total of 196 consecutive
      patients with epilepsy (epilepsy group, EG) with a mean age and standard
      deviation of 46.5 +/- 14.8 years and 66 subjects with no history of neurological
      or other chronic disorders (control group, CG) were assessed by the SSRS and
      neurologically. RESULTS: The SSRS scores of the EG and CG did not differ
      significantly (22.8 +/- 5.1 and 22.0 +/- 5.7, respectively). Patients with mesial
      temporal lobe epilepsy with hippocampal sclerosis (MTLE-HS) had significantly
      higher SSRS scores than those with other epileptic syndromes and, than in
      individuals of the CG. Multiple regression showed that the factors significantly
      associated with greater spirituality (greater SSRS score) for the EG, were lower
      education level, abnormal background EEG activity, and MTLE-HS. Other
      relationships with the clinical features of epilepsy and with the presence of
      psychiatric co-morbidity were not found. CONCLUSION: The present findings do not
      confirm a specific role of epilepsy in spirituality or of "epileptic
      hyperreligiosity," but suggest that spirituality in people with epilepsy is
      influenced by education level, and may also stem from epilepsy-related factors
      such as abnormal background EEG activity and the presence of MTLE-HS.

PMID- 24094728
TI  - Evaluation of human adenovirus and human polyomavirus as indicators of human
      sewage contamination in the aquatic environment.
AB  - Discharge of inadequately treated human wastewater into surface waters used for
      recreation, drinking water, irrigation and shellfish cultivation may present a
      public health hazard due to the potential shedding of high concentrations of
      pathogenic viruses from the human gastrointestinal tract. Human adenovirus (HAdV)
      and human polyomavirus (HPyV) are ubiquitous in humans and have excellent
      survival characteristics in the environment, so are potential candidates for
      indicators of human sewage contamination. Using qPCR assays, the prevalence and
      quantity of HAdV and HPyV JC and BK were determined in influent and effluent
      wastewater and receiving waters (river, urban stream, estuarine), then compared
      with norovirus (NoV) presence, a significant human pathogen which is not
      necessarily ubiquitously excreted into the environment. HAdV and HPyV were
      frequently detected in high concentrations in wastewater and wastewater
      contaminated waters confirming their use as potential indicators for the presence
      of human sewage. Overall, there was a correlation between the presence of HAdV
      and HPyV with NoV but there were some notable exceptions including the higher
      frequency of NoV compared to HAdV and HPyV in estuarine waters impacted by
      wastewater overflows. We found that HAdV and HPyV detection by qPCR was a
      suitable tool for evaluating water quality and that their detection can aid in
      determining pollution sources, thus providing useful information for health risk
      assessments. 

PMID- 24094729
TI  - Filtration properties of activated sludge in municipal MBR wastewater treatment
      plants are related to microbial community structure.
AB  - In the conventional activated sludge process, a number of important parameters
      determining the efficiency of settling and dewatering are often linked to
      specific groups of bacteria in the sludge--namely floc size, residual turbidity,
      shear sensitivity and composition of extracellular polymeric substances (EPS). In
      membrane bioreactors (MBRs) the nature of solids separation at the membrane has
      much in common with sludge dewaterability but less is known about the effect of
      specific microbial groups on the sludge characteristics that affect this process.
      In this study, six full-scale MBR plants were investigated to identify
      correlations between sludge filterability, sludge characteristics, and microbial
      community structure. The microbial community structure was described by
      quantitative fluorescence in situ hybridization and sludge filterability by a low
      pressure filtration method. A strong correlation between the degree of
      flocculation (ratio between floc size and residual turbidity) and sludge
      filterability at low pressure was found. A good balance between EPS and cations
      in the sludge correlated with good flocculation, relatively large sludge flocs,
      and low amounts of small particles and single cells in the bulk phase (measured
      as residual turbidity), all leading to a good filterability. Floc properties
      could also be linked to the microbial community structure. Bacterial species
      forming strong microcolonies such as Nitrospira and Accumulibacter were present
      in plants with good flocculation and filtration properties, while few strong
      microcolonies and many filamentous bacteria in the plants correlated with poor
      flocculation and filtration problems. In conclusion this study extends the
      hitherto accepted perception that plant operation affects floc properties which
      affects fouling. Additionally, plant operation also affects species composition,
      which affects floc properties and in the end fouling propensity.

PMID- 24094730
TI  - Arsenic species in drinking water wells in the USA with high arsenic
      concentrations.
AB  - Arsenic exists in ground water as oxyanions having two oxidation states, As(III)
      and As(V), and its concentrations vary widely and regionally across the United
      States (USA). Because of the difference in toxicity and removability of As(III)
      and As(V), arsenic speciation is important in the selection and design of an
      arsenic treatment systems. Identifying the arsenic species is also helpful in
      explaining and understanding the behavior and characteristics of arsenic in the
      environment. Although laboratory methods exist for speciating arsenic in water
      samples, the lack of a universal preservation method has led to the predominant
      use of field separation methods that are somewhat complex and costly. Thus, very
      few studies have incorporated arsenic speciation. A U.S. Environmental protection
      Agency (EPA) arsenic treatment research program provided a unique opportunity to
      speciate the naturally occurring arsenic in 65 well waters scattered across the
      USA with many of them being speciated monthly for up to three years. Speciation
      test data showed that 31 wells had predominantly As(V), 29 had predominantly
      As(III) and five had a mixture of both. A general pattern was found where As(III)
      was the dominant species in midwest ground waters where anoxic conditions and
      elevated iron concentrations prevailed and the well waters in the east, west and
      farwest had either As(III) or As(V) as the dominant species. The monthly (12-36)
      speciation tests results at many of these sites also found no major changes in
      arsenic species over time.

PMID- 24094731
TI  - Derivation of guideline values for gold (III) ion toxicity limits to protect
      aquatic ecosystems.
AB  - This study focused on estimating the toxicity values of various aquatic organisms
      exposed to gold (III) ion (Au(3+)), and to propose maximum guideline values for
      Au(3+) toxicity that protect the aquatic ecosystem. A comparative assessment of
      methods developed in Australia and New Zealand versus the European Community (EC)
      was conducted. The test species used in this study included two bacteria
      (Escherichia coli and Bacillus subtilis), one alga (Pseudokirchneriella
      subcapitata), one euglena (Euglena gracilis), three cladocerans (Daphnia magna,
      Moina macrocopa, and Simocephalus mixtus), and two fish (Danio rerio and Oryzias
      latipes). Au(3+) induced growth inhibition, mortality, immobilization, and/or
      developmental malformations in all test species, with responses being
      concentration-dependent. According to the moderate reliability method of
      Australia and New Zealand, 0.006 and 0.075 mg/L of guideline values for Au(3+)
      were obtained by dividing 0.33 and 4.46 mg/L of HC5 and HC50 species sensitivity
      distributions (SSD) with an FACR (Final Acute to Chronic Ratio) of 59.09. In
      contrast, the EC method uses an assessment factor (AF), with the 0.0006 mg/L
      guideline value for Au(3+) being divided with the 48-h EC50 value for 0.60 mg/L
      (the lowest toxicity value obtained from short term results) by an AF of 1000.
      The Au(3+) guideline value derived using an AF was more stringent than the SSD.
      We recommend that more toxicity data using various bioassays are required to
      develop more accurate ecological risk assessments. More chronic/long-term
      exposure studies on sensitive endpoints using additional fish species and
      invertebrates not included in the current dataset will be needed to use other
      derivation methods (e.g., US EPA and Canadian Type A) or the "High Reliability
      Method" from Australia/New Zealand. Such research would facilitate the
      establishment of guideline values for various pollutants that reflect the
      universal effects of various pollutants in aquatic ecosystems. To the best of our
      knowledge, this is the first study to suggest guideline values for Au(3+) levels
      permitted to enter freshwater environments.

PMID- 24094732
TI  - [Sacral fracture with spino-pelvic dissociation: a literature review].
AB  - The term, sacral fracture with traumatic spino-pelvic dissociation, is applied to
      those fractures of the sacrum in which there are both transverse and sagittal
      fracture lines in the sacrum, leading to a mechanical dissociation of the spine
      and the proximal fragment of the sacrum from the remaining sacrum and the pelvis.
      It is a quite rare pathological condition, and probably underdiagnosed. As it
      usually results from a high energy multiple trauma, an early diagnosis and
      treatment are mandatory for a better functional prognosis. We present a
      literature review of this relatively unknown injury.

PMID- 24094733
TI  - [Dislocation of the hip in a patient with von Recklinghausen disease].
AB  - Neurofibromatosis type 1 (NF-1) is one of the most common autosomal dominant
      disorders affecting humans. Patients with NF-1 may present with characteristic
      orthopaedic manifestations such as scoliosis, congenital pseudoarthrosis and limb
      hyperttrophy. Dislocation of the hip associated with NF-1 is a rare occurrence.
      There is a relative paucity of reported cases of pathological hip dislocation in
      patients with NF-1, with 13 documented cases found in the published literature.
      Seven dislocations occurred following trivial trauma and 6 cases were deemed
      atraumatic. We report a case of hip dislocation in a 26 years old male with NF-1
      and scoliosis, that was treated successfully by closed reduction and skin
      traction. 

PMID- 24094734
TI  - Development and implementation of a sepsis program.

PMID- 24094735
TI  - Caring for military children in the emergency department: the essentials.
AB  - The life of a military child has several challenges that can provide
      opportunities for resilience or risk for vulnerability. Nurses in emergent/urgent
      care may encounter military children when they are in a stressful transition such
      as during a move or deployment. Understanding the unique lifestyle of military
      children and implementing some key suggestions for practice can improve outcomes
      for this population. This article highlights the exceptional context of military
      children, military transitions, and opportunities to recognize families who are
      at risk and strategies to reach out using the I CARE (identify, correlate, ask,
      ready resources, and encourage) framework. 

PMID- 24094736
TI  - ED nursing in a Baghdad detainee camp: a personal perspective.

PMID- 24094737
TI  - Adult Moyamoya disease: 320-multidetector row CT for evaluation of
      revascularization in STA-MCA bypasses surgery.
AB  - PURPOSE: To evaluate the utility of 320-multidetector row whole-brain computed
      tomography perfusion (WBCTP) and whole-head subtracted dynamic angiography
      (WHSDCTA) for assessing the revascularization of blood flow after superficial
      temporal artery (STA) to middle cerebral artery (MCA) bypass surgery in adults
      with Moyamoya disease (MD) in the short and long term. PATIENTS AND METHODS: 320
      multidetector row WBCTP and WHSDCTA were applied in 20 patients with MD before
      and after surgery (for an average of 3 days and 3 months). The bypass arteries
      were investigated using WHSDCTA and compared with DSA. The regions of interests
      (ROIs) in the surgical and mirror sides of the cerebral cortex were drawn on a
      Vitrea Workstation. Cerebral blood volume (CBV), time to peak (TTP), cerebral
      blood flow (CBF), mean transit time (MTT), and delay time were recorded.
      Preoperative and postoperative perfusion parameters in the MCA distribution were
      compared using the paired t-test. RESULTS: WHSDCTA could clearly demonstrate 24
      bypass arteries in 26 arteries for 20 patients, results which were in accordance
      with the results of digital subtraction angiography (DSA). When comparing
      preoperative values to those within 3 days after surgery, only TTP and delay time
      were significantly different (P<0.05). Values of CBV, TTP, CBF, delay time, and
      MTT 3 months after surgery were significantly different (P<0.05) from those of
      preoperative perfusion. CONCLUSION: These data suggest that 320-multidetector row
      WBCTP and WHSDCTA can be used to evaluate the revascularization of blood flow
      after STA-MCA bypass surgery in patients with MD in the short and long term.

PMID- 24094738
TI  - Evaluation of nonionic adsorbent resins for removal of inhibitory compounds from
      corncob hydrolysate for ethanol fermentation.
AB  - The aim of this study was to investigate the effect of XAD4-column treatment on
      removal of several fermentation inhibitors from corncob hydrolysate (CH). From
      analysis using a model hydrolysate, more than 99% of 5-hydroxy-methyl furfural,
      furfural and vanillin were removed by this treatment, and more than 97% of the
      total xylose, glucose and arabinose remained in the detoxified CH (DCH). The
      resulting DCH was tested as a substrate for ethanol production by Saccharomyces
      cerevisiae and Pichia stipitis. The highest ethanol levels for S. cerevisiae were
      1.40 and 4.92 g l(-1) in CH and DCH, respectively. For P. stipitis, the levels
      were 0 and 4.73 g l(-1) in the CH and DCH media, respectively. The levels of
      alcohol volumetric productivity in the DCH medium were 0.374 and 0.200 g l(-1)h(
      1) for S. cerevisiae and P. stipitis, respectively.

PMID- 24094739
TI  - Clinical optimization of antigen specific modulation of type 1 diabetes with the
      plasmid DNA platform.
AB  - Some clinical trials in humans have aimed at modulation of type 1 diabetes (T1D)
      via alteration of the immune response to putative islet cell antigens,
      particularly proinsulin and insulin, glutamic acid decarboxylase and the peptide,
      DiaPep 277, derived from heat shock protein 60. The focus here is on development
      of a specially engineered DNA plasmid encoding proinsulin to treat T1D. The
      plasmid is engineered to turn off adaptive immunity to proinsulin. This approach
      yielded exciting results in a randomized placebo controlled trial in 80 adult
      patients with T1D. The implications of this trial are explored in regards to the
      potential for sparing inflammation in islets and thus allowing the functioning
      beta cells to recover and produce more insulin. Strategies to further strengthen
      the effects seen thus far with the tolerizing DNA plasmid to proinsulin will be
      elucidated. The DNA platform affords an opportunity for easy modifications. In
      addition standard exploration of dose levels, route of administration and
      frequency of dose are practical. Optimization of the effects seen to date on C
      peptide and on depletion of proinsulin specific CD8 T cells are feasible, with
      expected concomitant improvement in other parameters like hemoglobin A1c and
      reduction in insulin usage. T1D is one of the few autoimmune conditions where
      antigen specific therapy can be achieved, provided the approach is tested
      intelligently. Tolerizing DNA vaccines to proinsulin and other islet cell
      autoantigens is a worthy pursuit to potentially treat, prevent and to perhaps
      even 'cure' or 'prevent' type 1 diabetes.

PMID- 24094740
TI  - A molecular base for cell sorting at embryonic boundaries: contact inhibition of
      cadherin adhesion by ephrin/ Eph-dependent contractility.
AB  - The mechanism responsible for subdividing the embryo into individual tissues is a
      fundamental, yet still poorly understood, question in developmental biology.
      Various general hypotheses have been proposed, involving differences in cell
      adhesion, contractility, or contact-mediated repulsion. However, the key
      parameter in tissue separation, i.e., the regulation of cadherin-based adhesion
      at the boundary, has not yet been investigated. We show that cadherin clustering
      is specifically inhibited at the vertebrate notochord-presomitic mesoderm
      boundary, preventing formation of adhesive bonds between cells of the two
      different types. This local regulation depends on differentially expressed
      ephrins and Eph receptors, which increase cell contractility and generate a
      membrane blebbing-like behavior along the boundary. Inhibiting myosin activity is
      sufficient to induce cadherin clustering and formation of stable contacts across
      the boundary, causing notochord and presomitic tissues to fuse. Local inhibition
      of cadherin adhesion explains how sharp separation can be achieved in response to
      cell-cell contact signals. 

PMID- 24094741
TI  - A role for a dioxygenase in auxin metabolism and reproductive development in
      rice.
AB  - Indole-3-acetic acid (IAA), the natural auxin in plants, regulates many aspects
      of plant growth and development. Extensive analyses have elucidated the
      components of auxin biosynthesis, transport, and signaling, but the physiological
      roles and molecular mechanisms of auxin degradation remain elusive. Here, we
      demonstrate that the dioxygenase for auxin oxidation (DAO) gene, encoding a
      putative 2-oxoglutarate-dependent-Fe (II) dioxygenase, is essential for anther
      dehiscence, pollen fertility, and seed initiation in rice. Rice mutant lines
      lacking a functional DAO display increased levels of free IAA in anthers and
      ovaries. Furthermore, exogenous application of IAA or overexpression of the auxin
      biosynthesis gene OsYUCCA1 phenocopies the dao mutants. We show that recombinant
      DAO converts the active IAA into biologically inactive 2-oxoindole-3-acetic acid
      (OxIAA) in vitro. Collectively, these data support a key role of DAO in auxin
      catabolism and maintenance of auxin homeostasis central to plant reproductive
      development. 

PMID- 24094742
TI  - Identification of small exonic CNV from whole-exome sequence data and application
      to autism spectrum disorder.
AB  - Copy number variation (CNV) is an important determinant of human diversity and
      plays important roles in susceptibility to disease. Most studies of CNV carried
      out to date have made use of chromosome microarray and have had a lower size
      limit for detection of about 30 kilobases (kb). With the emergence of whole-exome
      sequencing studies, we asked whether such data could be used to reliably call
      rare exonic CNV in the size range of 1-30 kilobases (kb), making use of the eXome
      Hidden Markov Model (XHMM) program. By using both transmission information and
      validation by molecular methods, we confirmed that small CNV encompassing as few
      as three exons can be reliably called from whole-exome data. We applied this
      approach to an autism case-control sample (n = 811, mean per-target read depth =
      161) and observed a significant increase in the burden of rare (MAF <=1%) 1-30 kb
      CNV, 1-30 kb deletions, and 1-10 kb deletions in ASD. CNV in the 1-30 kb range
      frequently hit just a single gene, and we were therefore able to carry out
      enrichment and pathway analyses, where we observed enrichment for disruption of
      genes in cytoskeletal and autophagy pathways in ASD. In summary, our results
      showed that XHMM provided an effective means to assess small exonic CNV from
      whole-exome data, indicated that rare 1-30 kb exonic deletions could contribute
      to risk in up to 7% of individuals with ASD, and implicated a candidate pathway
      in developmental delay syndromes. 

PMID- 24094743
TI  - Fine Mapping and Identification of BMI Loci in African Americans.
AB  - Genome-wide association studies (GWASs) primarily performed in European-ancestry
      (EA) populations have identified numerous loci associated with body mass index
      (BMI). However, it is still unclear whether these GWAS loci can be generalized to
      other ethnic groups, such as African Americans (AAs). Furthermore, the putative
      functional variant or variants in these loci mostly remain under investigation.
      The overall lower linkage disequilibrium in AA compared to EA populations
      provides the opportunity to narrow in or fine-map these BMI-related loci.
      Therefore, we used the Metabochip to densely genotype and evaluate 21 BMI GWAS
      loci identified in EA studies in 29,151 AAs from the Population Architecture
      using Genomics and Epidemiology (PAGE) study. Eight of the 21 loci (SEC16B,
      TMEM18, ETV5, GNPDA2, TFAP2B, BDNF, FTO, and MC4R) were found to be associated
      with BMI in AAs at 5.8 * 10(-5). Within seven out of these eight loci, we found
      that, on average, a substantially smaller number of variants was correlated (r(2)
      > 0.5) with the most significant SNP in AA than in EA populations (16 versus 55).
      Conditional analyses revealed GNPDA2 harboring a potential additional independent
      signal. Moreover, Metabochip-wide discovery analyses revealed two BMI-related
      loci, BRE (rs116612809, p = 3.6 * 10(-8)) and DHX34 (rs4802349, p = 1.2 * 10(
      7)), which were significant when adjustment was made for the total number of SNPs
      tested across the chip. These results demonstrate that fine mapping in AAs is a
      powerful approach for both narrowing in on the underlying causal variants in
      known loci and discovering BMI-related loci. 

PMID- 24094745
TI  - Haplotype estimation using sequencing reads.
AB  - High-throughput sequencing technologies produce short sequence reads that can
      contain phase information if they span two or more heterozygote genotypes. This
      information is not routinely used by current methods that infer haplotypes from
      genotype data. We have extended the SHAPEIT2 method to use phase-informative
      sequencing reads to improve phasing accuracy. Our model incorporates the read
      information in a probabilistic model through base quality scores within each
      read. The method is primarily designed for high-coverage sequence data or data
      sets that already have genotypes called. One important application is phasing of
      single samples sequenced at high coverage for use in medical sequencing and
      studies of rare diseases. Our method can also use existing panels of reference
      haplotypes. We tested the method by using a mother-father-child trio sequenced at
      high-coverage by Illumina together with the low-coverage sequence data from the
      1000 Genomes Project (1000GP). We found that use of phase-informative reads
      increases the mean distance between switch errors by 22% from 274.4 kb to 328.6
      kb. We also used male chromosome X haplotypes from the 1000GP samples to simulate
      sequencing reads with varying insert size, read length, and base error rate. When
      using short 100 bp paired-end reads, we found that using mixtures of insert sizes
      produced the best results. When using longer reads with high error rates (5-20 kb
      read with 4%-15% error per base), phasing performance was substantially improved.

PMID- 24094744
TI  - Zebrafish Ciliopathy Screen Plus Human Mutational Analysis Identifies C21orf59
      and CCDC65 Defects as Causing Primary Ciliary Dyskinesia.
AB  - Primary ciliary dyskinesia (PCD) is caused when defects of motile cilia lead to
      chronic airway infections, male infertility, and situs abnormalities. Multiple
      causative PCD mutations account for only 65% of cases, suggesting that many genes
      essential for cilia function remain to be discovered. By using zebrafish
      morpholino knockdown of PCD candidate genes as an in vivo screening platform, we
      identified c21orf59, ccdc65, and c15orf26 as critical for cilia motility.
      c21orf59 and c15orf26 knockdown in zebrafish and planaria blocked outer dynein
      arm assembly, and ccdc65 knockdown altered cilia beat pattern. Biochemical
      analysis in Chlamydomonas revealed that the C21orf59 ortholog FBB18 is a
      flagellar matrix protein that accumulates specifically when cilia motility is
      impaired. The Chlamydomonas ida6 mutant identifies CCDC65/FAP250 as an essential
      component of the nexin-dynein regulatory complex. Analysis of 295 individuals
      with PCD identified recessive truncating mutations of C21orf59 in four families
      and CCDC65 in two families. Similar to findings in zebrafish and planaria,
      mutations in C21orf59 caused loss of both outer and inner dynein arm components.
      Our results characterize two genes associated with PCD-causing mutations and
      elucidate two distinct mechanisms critical for motile cilia function: dynein arm
      assembly for C21orf59 and assembly of the nexin-dynein regulatory complex for
      CCDC65. 

PMID- 24094746
TI  - Formation of chimeric genes by copy-number variation as a mutational mechanism in
      schizophrenia.
AB  - Chimeric genes can be caused by structural genomic rearrangements that fuse
      together portions of two different genes to create a novel gene. We hypothesize
      that brain-expressed chimeras may contribute to schizophrenia. Individuals with
      schizophrenia and control individuals were screened genome wide for copy-number
      variants (CNVs) that disrupted two genes on the same DNA strand. Candidate events
      were filtered for predicted brain expression and for frequency < 0.001 in an
      independent series of 20,000 controls. Four of 124 affected individuals and zero
      of 290 control individuals harbored such events (p = 0.002); a 47 kb duplication
      disrupted MATK and ZFR2, a 58 kb duplication disrupted PLEKHD1 and SLC39A9, a 121
      kb duplication disrupted DNAJA2 and NETO2, and a 150 kb deletion disrupted MAP3K3
      and DDX42. Each fusion produced a stable protein when exogenously expressed in
      cultured cells. We examined whether these chimeras differed from their parent
      genes in localization, regulation, or function. Subcellular localizations of
      DNAJA2-NETO2 and MAP3K3-DDX42 differed from their parent genes. On the basis of
      the expression profile of the MATK promoter, MATK-ZFR2 is likely to be far more
      highly expressed in the brain during development than the ZFR2 parent gene. MATK
      ZFR2 includes a ZFR2-derived isoform that we demonstrate localizes preferentially
      to neuronal dendritic branch sites. These results suggest that the formation of
      chimeric genes is a mechanism by which CNVs contribute to schizophrenia and that,
      by interfering with parent gene function, chimeras may disrupt critical brain
      processes, including neurogenesis, neuronal differentiation, and dendritic
      arborization. 

PMID- 24094748
TI  - Psychological, cognitive, and personal variables that predict college academic
      achievement among health sciences students.
AB  - BACKGROUND: There are many factors that affect college academic achievement among
      health sciences students. AIM: The aim of this study was to examine selected
      psychological, cognitive, and personal variables that affect students' academic
      achievement among health sciences college students in Saudi Arabia. METHOD: A
      correlational descriptive cross-sectional design was employed to collect data on
      the studied variables from 510 health sciences students (Medicine, Nursing,
      Respiratory Therapy, and Pharmacy Doctor) employing self-administered
      questionnaire. RESULTS: Results showed that students experienced low level of
      self-esteem and low level of student-faculty interaction; and high level of
      achievement motivation and satisfaction with life. Also, they reported mild
      levels of depression and stress and a moderate level of anxiety. Female students
      reported higher level of achievement motivation, depression, anxiety, and stress;
      while male students reported a higher level of self-esteem. Results also showed
      that achievement motivation, mothers' educational level, working besides
      studying, gender, aptitude test score, and depression level were the best
      predictors of academic achievement and accounting for 43% of the total variance.
      CONCLUSIONS: Several psychological, cognitive, and personal variables were found
      to affect college academic achievement among health sciences students.
      Recommendations and implications to enhance students' academic achievement are
      discussed.

PMID- 24094747
TI  - Mutations in AGBL1 cause dominant late-onset Fuchs corneal dystrophy and alter
      protein-protein interaction with TCF4.
AB  - Fuchs corneal dystrophy (FCD) is a hereditary dystrophy of the corneal
      endothelium and is responsible for majority of the corneal transplantation
      performed in the United States. Here, we describe three generations of a family
      with 12 individuals affected by late-onset FCD and in which three individuals are
      unaffected. Genome-wide mapping provided suggestive linkage at two loci on
      chromosomal arms 3p and 15q. Alleles at either locus alone were not sufficient to
      explain FCD; however, considered together, both loci could explain the disorder
      in this pedigree. Subsequent next-generation sequencing identified a nonsense
      mutation in AGBL1 in the 15q locus; this mutation would result in a premature
      termination of AGBL1. Consistent with a causal role for this transcript, further
      sequencing of our cohort of late-onset-FCD-affected individuals identified two
      cases harboring the same nonsense mutation and a further three unrelated
      individuals bearing a second missense allele. AGBL1 encodes a glutamate
      decarboxylase previously identified in serial analysis of gene expression of
      corneal endothelium, a finding confirmed by immunohistochemical staining. Wild
      type AGBL1 localizes predominantly to the cytoplasm; in sharp contrast, the
      truncated protein showed distinct nuclear localization. Finally, we show that
      AGBL1 interacts biochemically with the FCD-associated protein TCF4 and that the
      mutations found in our cohort of FCD individuals diminish this interaction. Taken
      together, our data identify a locus for FCD, extend the complex genetic
      architecture of the disorder, provide direct evidence for the involvement of TCF4
      in FCD pathogenesis, and begin to explain how causal FCD mutations affect
      discrete biochemical complexes. 

PMID- 24094749
TI  - Nurses' occupational health as a driver for curriculum change emphasising health
      promotion: an historical research study.
AB  - BACKGROUND: Reasons stated for curriculum change in nursing education are usually
      shifts in knowledge, care delivery, roles, regulatory standards and population
      health needs. In New Zealand in the 1930s, a curriculum change was driven instead
      by the need to protect and promote nurses' health. Tuberculosis was an
      international occupational health risk among nurses. Mary Lambie, New Zealand's
      chief nurse, considered nursing a "hazardous profession". One remedy she
      instituted was curriculum change in the national nurse training programme to
      emphasise health promotion among nurses. Global nursing issues today also impact
      on nurses' health. Curriculum changes again address this by promoting self-care
      and resilience. OBJECTIVE: To examine how international and national concern for
      nurses' occupational health drove a curriculum change in New Zealand nurse
      training in the 1930s. DESIGN: Historical Research METHODS: International
      occupational health reports (1930s), Lambie's annual reports (1932-1950), and
      questions and examiners' comments in a new state examination (1940s-1950s), were
      analysed to identify the reasons for and direction of the curriculum change.
      Findings were interpreted within international and national concerns and measures
      related to occupational health in nursing. RESULTS: Lambie used the political
      leverage of international and national worry over tuberculosis as a nursing
      occupational health risk to protect nurses' health more generally. In 1933 she
      revised the first year of the three-year national nursing curriculum to emphasise
      personal hygiene and bacteriology related to cross-infection, and in 1938
      introduced a State Preliminary Examination at the end of the first year of
      training to test this knowledge. Analysis of examinations, 1940s-1950s, confirms
      that the curriculum change driver was a concern to make nursing a less "hazardous
      profession". CONCLUSION: Nurse educators today should be aware of the variety of
      factors that can lead to curriculum change in nursing. In addition, concern for
      nurses' health today demonstrates the continuing need for health promotion in
      nursing curricula.

PMID- 24094750
TI  - Optimized superficially porous particles for protein separations.
AB  - Continuing interest in larger therapeutic molecules by pharmaceutical and biotech
      companies provides the need for improved tools for examining these molecules both
      during the discovery phase and later during quality control. To meet this need,
      larger pore superficially porous particles with appropriate surface properties
      (Fused-Core((r)) particles) have been developed with a pore size of 400 A,
      allowing large molecules (<500 kDa) unrestricted access to the bonded phase. In
      addition, a particle size (3.4 MUm) is employed that allows high-efficiency, low
      pressure separations suitable for potentially pressure-sensitive proteins. A
      study of the shell thickness of the new fused-core particles suggests a
      compromise between a short diffusion path and high efficiency versus adequate
      retention and mass load tolerance. In addition, superior performance for the
      reversed-phase separation of proteins requires that specific design properties
      for the bonded-phase should be incorporated. As a result, columns of the new
      particles with unique bonded phases show excellent stability and high
      compatibility with mass spectrometry-suitable mobile phases. This report includes
      fast separations of intact protein mixtures, as well as examples of very high
      resolution separations of larger monoclonal antibody materials and associated
      variants. Investigations of protein recovery, sample loading and dynamic range
      for analysis are shown. The advantages of these new 400 A fused-core particles,
      specifically designed for protein analysis, over traditional particles for
      protein separations are demonstrated.

PMID- 24094751
TI  - Simultaneous determination of polycyclic aromatic hydrocarbons and their
      chlorination by-products in drinking water and the coatings of water pipes by
      automated solid-phase microextraction followed by gas chromatography-mass
      spectrometry.
AB  - In this study, an automated method for the simultaneous determination of
      polycyclic aromatic hydrocarbons (PAHs) and their chlorination by-products in
      drinking water was developed based on online solid-phase microextraction-gas
      chromatography-mass spectrometry. The main focus was the optimisation of the
      solid-phase microextraction step. The influence of the agitation rate, type of
      fibre, desorption time, extraction time, extraction temperature, desorption
      temperature, and solvent addition was examined. The method was developed and
      validated using a mixture of 17 PAHs, 11 potential chlorination by-products
      (chlorinated and oxidised PAHs) and 6 deuterated standards. The limit of
      quantification was 10 ng/L for all target compounds. The validated method was
      used to analyse drinking water samples from three different drinking water
      distribution networks and the presumably coal tar-based pipe coatings of two pipe
      sections. A number of PAHs were detected in all three networks although
      individual compositions varied. Several PAH chlorination by-products
      (anthraquinone, fluorenone, cyclopenta[d,e,f]phenanthrenone, 3
      chlorofluoranthene, and 1-chloropyrene) were also found, their presence
      correlating closely with that of their respective parent compounds. Their
      concentrations were always below 100 ng/L. In the coatings, all PAHs targeted
      were detected although concentrations varied between the two coatings (76-12,635
      mg/kg and 12-6295 mg/kg, respectively). A number of chlorination by-products
      (anthraquinone, fluorenone, cyclopenta[d,e,f]phenanthrenone, 3
      chlorofluoranthene, and 1-chloropyrene) were also detected (from 40 to 985
      mg/kg), suggesting that the reaction of PAHs with disinfectant agents takes place
      in the coatings and not in the water phase after migration.

PMID- 24094752
TI  - Evaluation of passive samplers with neutral or ion-exchange polymer coatings to
      determine freely dissolved concentrations of the basic surfactant lauryl
      diethanolamine: Measurements of acid dissociation constant and organic carbon
      water sorption coefficient.
AB  - A passive sampler tool (solid-phase microextraction, SPME) was optimized to
      measure freely dissolved concentrations (Cw,free) of lauryl diethanolamine (C12
      DEA). C12-DEA can be protonated and act as a cationic surfactant. From the pH
      dependent sorption to neutral SPME coatings (polyacrylate and PDMS), a pKa of 8.7
      was calculated, which differs more than two units from the value of 6.4 reported
      elsewhere. Polyacrylate coated SPME could not adequately sample largely
      protonated C12-DEA in humic acid solutions of pH 6. A new hydrophobic SPME
      coating with cation-exchange properties (C18/SCX) sorbed C12-DEA 100 fold
      stronger than polyacrylate, because it specifically sorbs protonated C12-DEA
      species. The C18/SCX-SPME fiber showed linear calibration isotherms in a
      concentration range of <1 nM-1 MUM (well below the CMC). Using the C18/SCX-SPME
      fibers, linear sorption isotherms to Aldrich humic acid at pH 6 (ionic strength
      0.015 M) were measured over a broad concentration range with a sorption
      coefficient of 10(5.3).

PMID- 24094753
TI  - Multi-stir bar sorptive extraction for analysis of odor compounds in aqueous
      samples.
AB  - As reproducible coating of stir bars with more polar phases was found to be very
      difficult, a supporting grid was used in the development of an ethyleneglycol
      modified Silicone (EG Silicone) coated stir bar. This new polar coating showed
      good performance for the extraction of polar solutes, but long term use also
      showed degradation of the coating due to friction while stirring. In order to
      address the lower robustness of the EG Silicone stir bar which has a much softer
      coating compared to a conventional polydimethylsiloxane (PDMS) stir bar, a novel
      SBSE procedure termed multi-SBSE ((m)SBSE) was developed. (m)SBSE consists of the
      robust PDMS stir bar stirring at the bottom of the vial and the EG Silicone stir
      bar attached on the inner side wall of the vial (a magnetic clip is used for the
      set-up). After extraction, the two stir bars are placed in a single glass
      desorption liner and are simultaneously thermally desorbed. The desorbed
      compounds were analyzed by thermal desorption-gas chromatography-mass
      spectrometry (TD-GC-MS). Compared to conventional SBSE, (m)SBSE provides more
      uniform enrichment of a wide range of odor compounds in aqueous sample since both
      stir bars can complement each other, while eliminating the damage of the EG
      Silicone phase during the extraction. The robustness of the EG Silicone stir bar
      was dramatically increased and more than 30 extraction and desorption cycles were
      possible without loss in performance. The recoveries for polar solutes such as 2
      acetyl pyrrole (logKow: 0.55), benzyl alcohol (logKow: 1.08), guaiacol (logKow:
      1.34), and indole (logKow: 2.05) were increased by a factor of about 2-7. The
      (m)SBSE-TD-GC-MS method showed good linearity (r(2)>0.9913) and high sensitivity
      (limit of detection: 0.011-0.071 ng mL(-1)) for the test compounds spiked in
      water. The feasibility and benefit of the method was demonstrated with analysis
      of odor compounds in roasted green tea. The normalized areas obtained from
      (m)SBSE showed the best enrichment for most of the selected compounds compared to
      conventional SBSE using the PDMS stir bar or the EG Silicone stir bar. Fifteen
      compounds were determined in the range of 0.15-210 ng mL(-1) (RSD<14%, n=6).

PMID- 24094754
TI  - Alcohol challenge responses predict future alcohol use disorder symptoms: a 6
      year prospective study.
AB  - BACKGROUND: Propensity for alcohol misuse may be linked to an individuals'
      response to alcohol. This study examined the role of alcohol response phenotypes
      to future drinking problems. METHODS: One hundred four young heavy social
      drinkers participated in a within-subject, double-blind, placebo-controlled
      laboratory alcohol challenge study with 6-year follow-up. Participants were
      examined for subjective responses before and after receiving an intoxicating dose
      of alcohol (.8 g/kg) or a placebo beverage, given in random order. Follow-up was
      conducted in 5 waves over 6 years after the sessions to assess drinking behaviors
      and alcohol use disorder (AUD) symptoms. Retention was high with 98% (509 of 520)
      of possible follow-ups completed. RESULTS: Greater sensitivity to alcohol, in
      terms of stimulation and rewarding effects (like, want more) and lower
      sensitivity to alcohol sedation predicted greater number of AUD symptoms through
      6 years of follow-up. Cluster analyses revealed that for half the sample,
      increasing levels of stimulation and liking were predictors of more AUD symptoms
      with the other half divided between those showing like and want more and want
      more alone as significant predictors. CONCLUSIONS: The findings extend previous
      findings and offer new empirical insights into the propensity for excessive
      drinking and alcohol problems. Heightened alcohol stimulation and reward
      sensitivity robustly predicted more alcohol use disorder symptoms over time
      associated with greater binge-drinking frequency. These drinking problems were
      maintained and progressed as these participants were entering their third decade
      of life, a developmental interval when continued alcohol misuse becomes more
      deviant.

PMID- 24094755
TI  - Psychological distress and post-abortion contraceptive method effectiveness level
      chosen at an urban clinic.
AB  - OBJECTIVE: We investigated whether more psychological distress before an abortion
      is associated with the effectiveness of contraception selected (low, moderate, or
      high effectiveness) at an abortion clinic visit. METHOD: Using data from 253
      women attending an urban abortion clinic that primarily serves low-income women,
      we tested the association between pre-abortion psychological distress and the
      effectiveness level of post-abortion contraceptive choice. Based on typical use
      failure rates, we classified effectiveness of contraceptive choice into three
      levels-low, moderate, and high effectiveness. We measured psychological distress
      with four validated measures of depressive, anxious, and stress symptoms, and
      negative affect, as well as with a global measure comprising these four measures.
      We used multivariable ordinal logistic regression to measure the association of
      each psychological distress measure with post-abortion contraceptive method
      effectiveness level, adjusting for sociodemographic factors, pregnancy history,
      trimester of abortion, and importance of avoiding pregnancy in the next year.
      RESULTS: We found that compared to women experiencing less stress symptoms,
      negative affect and global psychological distress, women experiencing more stress
      symptoms [AOR=1.028, 95% CI: 1.001-1.050], negative affect [AOR=1.05, 95% CI:
      1.01-1.09] and global psychological distress [AOR=1.46, 95% CI: 1.09-1.95] were
      more likely to choose more effective versus less effective methods, p<.05, in
      adjusted models. Using dichotomous psychological measures we found similar
      results. CONCLUSIONS: Women experiencing more psychological distress before an
      abortion selected more effective contraceptive methods after their abortion.
      Future research should examine whether this distress is associated with
      subsequent contraceptive use or continuation. IMPLICATIONS: The current study
      suggests that contraceptive providers should not assume that women experiencing
      more psychological distress prefer to use less effective contraceptive methods.

PMID- 24094757
TI  - [Evaluation of an educational program for oral anticoagulation in children with
      the INR home-monitoring CoaguChek XS((r))].
AB  - OBJECTIVE: To assesses the results of our education program relative to
      anticoagulation therapy and self-monitoring of INR. MATERIALS AND METHODS: All
      children treated with oral anticoagulation therapy and followed using INR self
      monitoring in Tours and Nantes, France, were included. A questionnaire on the
      treatment and its management was sent to the patients and their family. We
      analyzed the quality of anticoagulation using the proportion of INR within the
      target range. RESULTS: Thirty-three children were included, with a mean age of
      10.9years. Thirty-one questionnaires could be analyzed. Insufficient knowledge on
      the treatment objective and risks, the INR target range, and the interpretation
      of the INR was observed. We found 65.8% of INRs within the target range. The
      proportion of INRs within the target range was better with the INR self-testing
      than with the laboratory test (69.7% vs. 49.1%, P=0.003). There was no major
      complication observed during the study period. A moderate correlation (K=0.57)
      was noted between the INRs measured with the point-of-care monitor and the
      laboratory test on the same day. CONCLUSION: However, home-monitoring of oral
      anticoagulation therapy increases the quality of anticoagulation. Both education
      and the training program need improvement in order to provide patients and their
      families with better knowledge on anticoagulation therapy.

PMID- 24094756
TI  - Vitamin D: non-skeletal actions and rational use.
AB  - Recent years have witnessed a substantial increase in the number of seric
      determinations of vitamin D, in a worldwide basis. At Hospital das Clinicas of
      Faculdade de Medicina of Universidade de Sao Paulo that increase reached 700%
      over the last four years. Nevertheless there are many controversies on the
      literature about the role of vitamin D in conditions unrelated to the
      musculoskeletal system. In this study the metabolism, sources and actions of
      vitamin D on the body are reviewed. Observational studies, clinical trials,
      systematic reviews and metanalysis which focused on the relationship between the
      vitamin and conditions such as cancer, cardiovascular disease, diabetes and falls
      were searched on the literature, analyzed and discussed. Results are presented as
      quiz and answer, tables and a figure. The role of vitamin D on the above
      mentioned conditions is discussed, and the controversial issues stressed. 

PMID- 24094758
TI  - [Treatment of severe and uncomplicated falciparum malaria in children in France].
AB  - Quinine was the main treatment for malaria between 1630 and the beginning of the
      XXth century. In the 1940s, the synthesis of chloroquine gave rise to the hope of
      eliminating this plague. Falciparum resistance to chloroquine, first observed in
      Asia then in sub-Saharan Africa, lead researchers to discover halofantrine,
      mefloquine, atovaquone-proguanil and artemisinin combined therapies. There is no
      ideal treatment for uncomplicated imported malaria in children. Medical teams
      have to develop a protocol according to available drugs and their personal
      experience, with a special attention to follow-up at days 3-4 and day 28. From
      now on, severe malaria must be treated with intravenous artesunate, a more
      effective therapy than quinine. 

PMID- 24094759
TI  - [Congenital insensitivity to pain: clinical and neurophysiological study in three
      sisters of a Moroccan family].
AB  - Congenital insensitivity to pain is a rare hereditary sensory and autonomic
      neuropathy (HSAN). This disorder is an autosomal recessive condition: since 1996,
      mutations attributed to this entity have been found in the neurotrophin tyrosine
      kinase gene receptor on chromosome 1. The authors report 3 cases of congenital
      insensitivity to pain. In these 3 sisters of consanguineous parents, the clinical
      investigation showed total absence of pain and temperature sensations with
      preservation of all other sensory modalities, mental retardation, but in contrast
      to HSAN type IV, there was no anhidrosis. The neurophysiological investigation
      revealed an isolated axonal sensory polyneuropathy in the 3 patients. The
      clinical and neurophysiological investigations were normal in both parents and
      the brother. The physiopathology of this entity is discussed. We suggest a
      particular form of HSAN type IV with preservation of transpiration or a new
      entity of congenital insensitivity to pain, which should be analyzed genetically.

PMID- 24094760
TI  - Etiology and outcome of hydrops fetalis: report of 62 cases.
AB  - AIM: We aimed to define the etiologic and prognostic factors in live-born infants
      with hydrops fetalis (HF) in our tertiary neonatal intensive care unit over a 10
      year period. METHODS: Medical records of newborn infants with HF during 2002-2011
      were reviewed retrospectively. Demographic data, prenatal interventions, clinical
      and laboratory findings, outcomes, and the results of postmortem examinations
      were analyzed. RESULTS: During the study period, 62 newborn infants with HF were
      identified from 16,200 live-born deliveries and the incidence of HF was 3.8/1000
      live births in our hospital. Twenty-eight infants (45.2%) had immune HF, whereas
      34 (54.8%) had nonimmune HF. An etiologic factor could be identified in 24
      (70.5%) infants with nonimmune HF. Lymphatic dysplasias comprised the majority
      (23.5%) of the infants with nonimmune HF. Mortality rate was 50%. The presence of
      two or more serous cavity effusions and gestational age were independently
      associated with the risk of mortality. CONCLUSION: Despite the improvements in
      neonatal care, mortality rate in infants with HF is still high. Gestational age
      and the extent of serous cavity determine the risk of mortality. Timely and
      advanced prenatal or postnatal new therapeutic strategies may alter this fatal
      outcome in appropriate patients.

PMID- 24094761
TI  - The public disclosure of accreditation information in Australia: stakeholder
      perceptions of opportunities and challenges.
AB  - Public disclosure is increasingly a requirement of accrediting agencies and
      governments. There are few published empirical evaluations of disclosure
      interventions that inform evidence-based implementation or policy. This study
      investigated the practices associated with the public disclosure of healthcare
      accreditation information, in addition to multi-stakeholder perceptions of key
      challenges and opportunities for improvement. We conducted a mixed methods study
      comprising analysis of disclosure practices by accreditation agencies, and 47
      semi-structured individual or group interviews involving 258 people. Participants
      were diverse stakeholders associated with Australian primary, acute and
      residential aged care accreditation programmes. Four interrelated issues were
      identified. First, there was broad agreement that accreditation information
      should be publicly disclosed, although the three accreditation agencies differed
      in the information they made public. Second, two implementation issues emerged:
      the need to educate the community about accreditation information, and the
      practical question of the detail to be provided. Third, the impact, both positive
      and negative, of disclosing accreditation information was raised. Fourth, the
      lack of knowledge about the impact on consumers was discussed. Public disclosure
      of accreditation information is an idea that has widespread support. However,
      translating the idea into practice, so as to produce appropriate, meaningful
      information, is a challenge. 

PMID- 24094762
TI  - Cat scratches or flea feces?

PMID- 24094764
TI  - Primary hemostasis in neonates with thrombocytopenia.
AB  - OBJECTIVE: To evaluate the relationship between platelet counts and the platelet
      function analyzer-100 closure times (CTs) in neonates with thrombocytopenia, and
      to determine what other factors significantly affect CTs. STUDY DESIGN: In a
      single institution prospective cross-sectional study, blood samples from neonates
      with platelet counts <150 * 10(9)/L were tested on the platelet function analyzer
      100 with CT-collagen/epinephrine (CT-Epi) and CT-collagen/adenosine diphosphate
      (CT-ADP) cartridges. RESULTS: The mean platelet count was 95 +/- 28 * 10(9)/L for
      48 infants with a mean gestational age 30.9 +/- 5.3 weeks and median postnatal
      age of 5 (3-18) days. No association was evident between CT-Epi and platelet
      count. However, the CT-ADP was prolonged in many (but not all) infants with
      platelet counts <90 * 10(9)/L. Among infants <32 weeks gestational age, we found
      a moderate negative correlation between CT-ADP and platelet count (r = -0.54, P =
      .0045). The negative correlation was strongest in infants <32 weeks and <10 days
      old (r = -0.8, P = .0017). Other variables examined (hematocrit, infection, Score
      of Neonatal Acute Physiology II) did not have a significant effect on CT-ADP in a
      linear regression model. CONCLUSIONS: Platelet counts <90 * 10(9)/L are
      associated with prolonged CT-ADP times in some but not all infants. Gestational
      and postnatal age-related differences in platelet function account for some of
      this variability. The predictive value of CT-ADP on neonatal bleeding risk
      remains to be studied.

PMID- 24094765
TI  - A 2-month-old boy with desquamative skin fold dermatitis.

PMID- 24094766
TI  - Angiogenesis in gastric cancer: hitting the target?

PMID- 24094763
TI  - More physically active and leaner adolescents have higher energy intake.
AB  - OBJECTIVE: To test whether youths who engage in vigorous physical activity are
      more likely to have lean bodies while ingesting relatively large amounts of
      energy. For this purpose, we studied the associations of both physical activity
      and adiposity with energy intake in adolescents. STUDY DESIGN: The study subjects
      were adolescents who participated in 1 of 2 cross-sectional studies, the Healthy
      Lifestyle in Europe by Nutrition in Adolescence (HELENA) study (n = 1450; mean
      age, 14.6 years) or the European Youth Heart Study (EYHS; n = 321; mean age, 15.6
      years). Physical activity was measured by accelerometry, and energy intake was
      measured by 24-hour recall. In the HELENA study, body composition was assessed by
      2 or more of the following methods: skinfold thickness, bioelectrical impedance
      analysis, plus dual-energy X-ray absorptiometry or air-displacement
      plethysmography in a subsample. In the EYHS, body composition was assessed by
      skinfold thickness. RESULTS: Fat mass was inversely associated with energy intake
      in both studies and using 4 different measurement methods (P <= .006). Overall,
      fat-free mass was positively associated with energy intake in both studies, yet
      the results were not consistent across measurement methods in the HELENA study.
      Vigorous physical activity in the HELENA study (P < .05) and moderate physical
      activity in the EYHS (P < .01) were positively associated with energy intake.
      Overall, results remained unchanged after adjustment for potential confounding
      factors, after mutual adjustment among the main exposures (physical activity and
      fat mass), and after the elimination of obese subjects, who might tend to
      underreport energy intake, from the analyses. CONCLUSION: Our data are consistent
      with the hypothesis that more physically active and leaner adolescents have
      higher energy intake than less active adolescents with larger amounts of fat
      mass.

PMID- 24094769
TI  - Running interference to lower cholesterol.

PMID- 24094768
TI  - Ramucirumab monotherapy for previously treated advanced gastric or gastro
      oesophageal junction adenocarcinoma (REGARD): an international, randomised,
      multicentre, placebo-controlled, phase 3 trial.
AB  - BACKGROUND: Vascular endothelial growth factor (VEGF) and VEGF receptor-2 (VEGFR
      2)-mediated signalling and angiogenesis can contribute to the pathogenesis and
      progression of gastric cancer. We aimed to assess whether ramucirumab, a
      monoclonal antibody VEGFR-2 antagonist, prolonged survival in patients with
      advanced gastric cancer. METHODS: We did an international, randomised, double
      blind, placebo-controlled, phase 3 trial between Oct 6, 2009, and Jan 26, 2012,
      at 119 centres in 29 countries in North America, Central and South America,
      Europe, Asia, Australia, and Africa. Patients aged 24-87 years with advanced
      gastric or gastro-oesophageal junction adenocarcinoma and disease progression
      after first-line platinum-containing or fluoropyrimidine-containing chemotherapy
      were randomly assigned (2:1), via a central interactive voice-response system, to
      receive best supportive care plus either ramucirumab 8 mg/kg or placebo,
      intravenously once every 2 weeks. The study sponsor, participants, and
      investigators were masked to treatment assignment. The primary endpoint was
      overall survival. Analysis was by intention to treat. This trial is registered
      with ClinicalTrials.gov, number NCT00917384. FINDINGS: 355 patients were assigned
      to receive ramucirumab (n=238) or placebo (n=117). Median overall survival was
      5.2 months (IQR 2.3-9.9) in patients in the ramucirumab group and 3.8 months (1.7
      7.1) in those in the placebo group (hazard ratio [HR] 0.776, 95% CI 0.603-0.998;
      p=0.047). The survival benefit with ramucirumab remained unchanged after
      multivariable adjustment for other prognostic factors (multivariable HR 0.774,
      0.605-0.991; p=0.042). Rates of hypertension were higher in the ramucirumab group
      than in the placebo group (38 [16%] vs nine [8%]), whereas rates of other adverse
      events were mostly similar between groups (223 [94%] vs 101 [88%]). Five (2%)
      deaths in the ramucirumab group and two (2%) in the placebo group were considered
      to be related to study drug. INTERPRETATION: Ramucirumab is the first biological
      treatment given as a single drug that has survival benefits in patients with
      advanced gastric or gastro-oesophageal junction adenocarcinoma progressing after
      first-line chemotherapy. Our findings validate VEGFR-2 signalling as an important
      therapeutic target in advanced gastric cancer. FUNDING: ImClone Systems.

PMID- 24094767
TI  - Effect of an RNA interference drug on the synthesis of proprotein convertase
      subtilisin/kexin type 9 (PCSK9) and the concentration of serum LDL cholesterol in
      healthy volunteers: a randomised, single-blind, placebo-controlled, phase 1
      trial.
AB  - BACKGROUND: Proprotein convertase subtilisin/kexin type 9 (PCSK9) binds to LDL
      receptors, leading to their degradation. Genetics studies have shown that loss-of
      function mutations in PCSK9 result in reduced plasma LDL cholesterol and
      decreased risk of coronary heart disease. We aimed to investigate the safety and
      efficacy of ALN-PCS, a small interfering RNA that inhibits PCSK9 synthesis, in
      healthy volunteers with raised cholesterol who were not on lipid-lowering
      treatment. METHODS: We did a randomised, single-blind, placebo-controlled, phase
      1 dose-escalation study in healthy adult volunteers with serum LDL cholesterol of
      3.00 mmol/L or higher. Participants were randomly assigned in a 3:1 ratio by
      computer algorithm to receive one dose of intravenous ALN-PCS (with doses ranging
      from 0.015 to 0.400 mg/kg) or placebo. The primary endpoint was safety and
      tolerability of ALN-PCS. Secondary endpoints were the pharmacokinetic
      characteristics of ALN-PCS and its pharmacodynamic effects on PCSK9 and LDL
      cholesterol. Study participants were masked to treatment assignment. Analysis was
      per protocol and we used ANCOVA to analyse pharmacodynamic endpoint data. This
      trial is registered with ClinicalTrials.gov, number NCT01437059. FINDINGS: Of 32
      participants, 24 were randomly allocated to receive a single dose of ALN-PCS
      (0.015 mg/kg [n=3], 0.045 mg/kg [n=3], 0.090 mg/kg [n=3], 0.150 mg/kg [n=3],
      0.250 mg/kg [n=6], or 0.400 mg/kg [n=6]) and eight to placebo. The proportions of
      patients affected by treatment-emergent adverse events were similar in the ALN
      PCS and placebo groups (19 [79%] vs seven [88%]). ALN-PCS was rapidly
      distributed, with peak concentration and area under the curve (0 to last
      measurement) increasing in a roughly dose-proportional way across the dose range
      tested. In the group given 0.400 mg/kg of ALN-PCS, treatment resulted in a mean
      70% reduction in circulating PCSK9 plasma protein (p<0.0001) and a mean 40%
      reduction in LDL cholesterol from baseline relative to placebo (p<0.0001).
      INTERPRETATION: Our results suggest that inhibition of PCSK9 synthesis by RNA
      interference (RNAi) provides a potentially safe mechanism to reduce LDL
      cholesterol concentration in healthy individuals with raised cholesterol. These
      results support the further assessment of ALN-PCS in patients with
      hypercholesterolaemia, including those being treated with statins. This study is
      the first to show an RNAi drug being used to affect a clinically validated
      endpoint (ie, LDL cholesterol) in human beings. FUNDING: Alnylam Pharmaceuticals.

PMID- 24094770
TI  - Loss of cardiac resynchronization during DDD pacing: what is the mechanism?

PMID- 24094771
TI  - Field and laboratory assessments on dissolution and fractionation of Pb from
      spent and unspent shots in the rhizosphere soil.
AB  - The objective of this study was to determine the effect of plant root growth on
      Pb dissolution from shot under laboratory and field-scale conditions. For a
      laboratory study, a 100-d incubation experiment was conducted to assess Pb
      dissolution from unspent shot (new) and spent shot (>10yr in fields) in
      rhizosphere and non-rhizosphere (bulk) soils using the Toxicity Characteristic
      Leaching Procedure (TCLP) and sequential extraction methods. This study found
      that increasing the soil pH value to 7.5 by liming significantly reduced Pb
      dissolution from unspent and spent shot (<5mgL(-1)). Dissolution of Pb from shot
      was induced more in rhizosphere than bulk soils. Regardless of shot types, the
      averaged TCLP-Pb concentration in acidic and limed soils was 12.9- and 8.1-fold
      greater in rhizosphere than in bulk soils, respectively. For a field-scale
      investigation, a total of 31 individual plant samples of 6 different species and
      their rhizosphere soils were collected from a clay-target shooting range
      (<35000mgPbkg(-1)). The Pb concentration in plant aboveground tissues depended on
      species with a mean value of 72mgkg(-1) (15-254mgkg(-1)), which was far smaller
      than that reported in previous studies. Regardless of high soil Pb levels,
      aboveground tissue Pb concentrations of Solidago altissima (i.e., Canada
      goldenrod, 15mgkg(-1)) and Andropogon virginicus (i.e., broomsedge, 18mgkg(-1))
      were below the toxicity threshold, suggesting that these indigenous species could
      have phytostabilization potentials. The limited Pb accumulation by vegetation was
      attributed to the abundance of soil calcite derived from spent clay-target
      fragments. 

PMID- 24094772
TI  - Degradation of polychlorinated naphthalene by mechanochemical treatment.
AB  - Polychlorinated naphthalene (PCN) is a hazardous compound that is listed as a new
      persistent organic pollutants candidate by the United Nations Environment
      Program. The production, import and use of PCNs are prohibited by the Chemical
      Substances Control Law in Japan. PCN was milled with calcium oxide as an additive
      to investigate the feasibility of its degradation by mechanochemical treatment.
      The milling process cleaved the C-C and C-Cl bonds by the mechanically induced
      solid-state reaction. Gas chromatography/mass spectrometry analysis confirmed
      that the PCN was decomposed after 1h milling. The yield of chloride ions reached
      100% after 3h milling. This indicates that all PCN was broken down into inorganic
      compounds after milling, thereby maintaining the chlorine mass balance through
      the reaction. This experiment, for the first time, exhibited the effectiveness of
      mechanochemical treatment as a PCN degradation method. 

PMID- 24094774
TI  - Adsorption of antibiotic ciprofloxacin on carbon nanotubes: pH dependence and
      thermodynamics.
AB  - The environmental risks of antibiotics have attracted increasing research
      attention, but their environmental behaviors remain unclear. In this study,
      functionalized carbon nanotubes (CNTs), namely, hydroxylized (MH), carboxylized
      (MC), graphitized multi-walled CNTs (MG) and single-walled CNTs (SW) were used as
      adsorbents and ciprofloxacin (CIP) as an adsorbate to investigate the effect of
      pH and temperature on sorption and desorption processes. Sorption isotherms of
      CIP were fitted well by Freundlich and Dubinin-Ashtakhov models. Highly nonlinear
      isotherms of CIP were observed, indicating the highly heterogeneous site energy
      distribution on CNTs. At all pHs, SW had the highest sorption for CIP due to its
      largest surface area among all CNTs. Sorption distinction between MH and MC was
      explained by pi-pi electron donor-acceptor interactions. For SW, CIP sorption was
      thermodynamically favorable and endothermic associated with an entropy driven
      process, while the reverse process occurred for MC and MG. The rearrangement of
      CNTs bundles/aggregates and covalent bond formation may be responsible for CIP
      desorption hysteresis on CNTs. Desorption of antibiotics from CNTs may lead to
      potential exposure, particularly under changing environmental conditions such as
      temperature and pH. 

PMID- 24094773
TI  - Expression alterations of cytochromes P4501A1, 2E1, and 3A, and their receptors
      AhR and PXR caused by 1-octyl-3-methylimidazolium chloride in mouse mammary
      carcinoma cells.
AB  - Cytochrome P450s (CYPs) play a key role in the metabolism of a wide range of
      environmental xenobiotics and endogenous compounds. The expression and activity
      levels of CYPs can be elevated by a process of induction involving the activation
      of nuclear receptors. The effects of the ionic liquid 1-octyl-3-methylimidazolium
      chloride ([C(8)mim][Cl]) on the expression of cytochrome P450 members, including
      CYP1A1, CYP2E1, and CYP3A, as well as on aryl hydrocarbon receptor (AhR) and
      pregnane X receptor (PXR) in mouse mammary carcinoma cells (EMT6) were
      investigated by using quantitative real-time PCR in the present study. The
      results reveal that [C(8)mim][Cl]-exposure up-regulates the expressions of
      CYP1A1, CYP2E1, and CYP3A at mRNA level, suggesting that imidazolium-based ionic
      liquids can activate CYPs. Our results also suggest that [C(8)mim][Cl]-mediated
      CYP3A induction be PXR-dependent. This result may be beneficial to evaluating the
      environmental toxicity of imidazolium-based ionic liquids and investigating the
      metabolism of imidazolium-derivative drugs.

PMID- 24094775
TI  - Sleeping too close together: obesity and obstructive sleep apnea in childhood and
      adolescence.
AB  - To review the current available literature exploring the prevalence, severity,
      consequences and treatments for obesity related OSA in children and adolescents.
      The published literature was searched through EMBASE and Pubmed using a pre
      defined search strategy. There is evidence showing that OSA occurs more
      frequently and may be more severe in children and adolescents who are overweight
      or obese compared with lean children. Obesity and OSA are independently
      associated with adverse cardiovascular, metabolic, and neuropsychological
      consequences. The magnitude of these abnormalities when obesity and OSA co-exist
      is not well established. Treatment options for obesity related OSA includes
      adenotonsillectomy, but it does not cure OSA in over 50% of obese children.
      Positive airway pressure (PAP) therapy delivered through continuous or bi-level
      modes is successful, but limited by generally poor compliance. There is
      increasing experience with bariatric surgical techniques which are effective for
      the treatment of obesity and its related complications. As obesity related OSA is
      highly prevalent, more research is needed to understand the interaction of these
      two conditions with regards to pathophysiology, adverse consequences and optimal
      management strategies. 

PMID- 24094776
TI  - Environmental determinants of the spatial distribution of Echinococcus
      multilocularis in Hungary.
AB  - Human alveolar echinococcosis, caused by the metacestode stage of Echinococcus
      multilocularis, is one of the most pathogenic zoonoses in the temperate and
      arctic region of the Northern Hemisphere. To investigate the spatial distribution
      of E. multilocularis and the factors influencing this distribution in the
      recently identified endemic area of Hungary, 1612 red fox (Vulpes vulpes)
      carcasses were randomly collected from the whole Hungarian territory from
      November 2008 to February 2009 and from November 2012 to February 2013. The
      topographic positions of foxes were recorded in geographic information system
      database. The digitized home ranges and the vector data were used to calculate
      the altitude, mean annual temperature, annual precipitation, soil water
      retention, soil permeability, areas of land cover types and the presence and
      buffer zone of permanent water bodies within the fox territories. The intestinal
      mucosa from all the foxes was tested by sedimentation and counting technique.
      Multiple regression analysis was performed with environmental parameter values
      and E. multilocularis counts. The spatial distribution of the parasite was
      clumped. Based on statistical analysis, mean annual temperature and annual
      precipitation were the major determinants of the spatial distribution of E.
      multilocularis in Hungary. It can be attributed to the sensitivity of E.
      multilocularis eggs to high temperatures and desiccation. Although spreading and
      emergence of the parasite was observed in Hungary before 2009, the prevalence and
      intensity of infection did not change significantly between the two collection
      periods. It can be explained by the considerably lower annual precipitation
      before the second collection period. 

PMID- 24094777
TI  - Intermediate and paratenic hosts in the life cycle of Aelurostrongylus abstrusus
      in natural environment.
AB  - The cat lungworm Aelurostrongylus abstrusus affects the domestic cats and other
      felids all over the world. Feline aelurostrongylosis is of importance in clinical
      feline medicine. Snails and slugs are the intermediate hosts, but the cat is
      probably infected by eating paratenic hosts, e.g., rodents, birds, amphibians and
      reptiles. Herein we present the first finding of A. abstrusus in a naturally
      infected invasive synantropic slugs Arion lusitanicus (intermediate host) and
      wild living rodents Apodemus agrarius (paratenic host). The results confirm the
      usefulness of molecular approaches for investigating the biology, ecology and
      epidemiology of A. abstrusus, the agent of feline aelurostrongylosis.

PMID- 24094778
TI  - Adolescents' level of eating psychopathology is related to perceptions of their
      parents' current feeding practices.
AB  - PURPOSE: This study aimed to examine the relationships between adolescents'
      eating disorder attitudes and their perceptions of the feeding practices that
      their parents/caregivers currently use. METHODS: Boys and girls (N = 528) aged 13
      15 completed self-report measures of their levels of eating psychopathology and
      their parents' current feeding practices and reported their own height and
      weight. RESULTS: For girls, greater perceived pressure from parents to eat food
      and lower perceived parental responsibility for food were significantly related
      to more unhealthy eating-related attitudes. Similar to girls, lower perceived
      parental responsibility for food was significantly related to greater levels of
      eating psychopathology in boys. Greater perceived parental restriction of foods
      was also significantly related to greater eating psychopathology in boys.
      CONCLUSIONS: These results suggest that adolescents' perceptions of their
      parents' use of more controlling feeding practices are related to greater
      prevalence of unhealthy eating-related attitudes. Such findings have potentially
      important implications for the prevention of disordered eating in adolescents.

PMID- 24094779
TI  - The theory-practice gap in cognitive-behavior therapy.
AB  - This special series is devoted to understanding the theory-practice gap in
      cognitive-behavior therapy (CBT). Although CBT enjoys considerable empirical
      support, and is widely recognized as an efficacious approach to a diversity of
      psychiatric disorders and includes many different forms of treatment, it is
      unclear whether clinicians are familiar with the underlying theories of the
      treatments they are practicing. Moreover, it is unclear to what degree an
      understanding of the theory is necessary for effective practice. Gaining clarity
      on the role of understanding underlying theory and identifying potential
      disparities between theory and practice may have implications for the way
      graduate training programs are structured and current professionals approach
      continuing education. A brief exploration of these implications will be offered
      by introducing issues related to the scientist-practitioner model and
      dissemination of efficacious treatments, in addition to an outline of potential
      advantages and disadvantages of knowing underlying theory. This special series
      will then feature several major approaches to treatment wherein the role of
      theory and practice are discussed. 

PMID- 24094780
TI  - The practice of exposure therapy: relevance of cognitive-behavioral theory and
      extinction theory.
AB  - Exposure therapy is the most effective psychological intervention for people with
      anxiety disorders. While many therapists learn how to implement exposure
      techniques through clinical training programs or instructional workshops, not all
      of these educational efforts include a focus on the theory underlying this
      treatment. The availability of treatment manuals providing step-by-step
      instructions for how to implement exposure makes it easier for clinicians to use
      these techniques with less training than they might otherwise receive. This
      raises questions regarding whether it is necessary to understand the theory
      behind the use of exposure. This article argues that knowledge of the relevant
      theory is crucial to being able to implement exposure therapy in ways that
      optimize both short- and long-term outcome. Specific ways in which theory is
      relevant to using exposure techniques are discussed. 

PMID- 24094781
TI  - The theory-practice gap in cognitive behavioral therapy: reflections and a modest
      proposal to bridge the gap.
AB  - This paper examines the issues related to the gap between theory and practice in
      the area of cognitive-behavioral therapy. The article begins with a review of the
      evidence for such a gap, and having demonstrated that the gap exists, provides a
      discussion of some of the factors that are likely important in its genesis and
      maintenance. The article then focuses on potential strategies to reduce the
      theory-practice gap that go beyond the common recommendation for both efficacy
      and effectiveness research. In particular, we provide recommendations for
      protocol planning and design, training and competency maintenance, dissemination
      research, and implementation and policy change. We conclude with the proposition
      that theory and research should not only inform practice, but that practice
      should have a reciprocal benefit on theory and research. 

PMID- 24094782
TI  - What must you know and do to get good outcomes with DBT?
AB  - Because little research has been conducted on which therapist-client interactions
      lead to intermediate and end-point improvements in Dialectical Behavior Therapy
      (DBT), we have a small evidence-base from which to specify what therapists must
      know and do in order to obtain good outcomes using DBT. As with other evidence
      based practices, dissemination of DBT has defaulted to assumptions and methods
      from the "psychotherapy technology model," which emphasizes transfer of the
      validated treatment package from the research clinic to routine settings with
      high fidelity (Morgenstern & McKay, 2007). However, serious limitations of the
      psychotherapy technology model require pursuit of alternative complementary
      models to guide dissemination. One complementary approach is to use well-designed
      practice-based training research. In this approach, therapists learn modular
      competencies linked to a highly structured yet flexible clinical decision-making
      framework. Modular training of therapist competencies emphasizes the continuity
      of the component therapist strategies across evidence-based protocols rather than
      emphasizing the packages or manuals as separate and distinct. Key hypotheses
      about the change processes responsible for client change and the associated
      treatment strategies used to influence these change processes should be specified
      and measured at the level of client, therapist, and service delivery setting.
      Adopting this approach may offer advantages that apply to the dissemination and
      implementation of DBT and other evidence-based practices (EBPs). 

PMID- 24094783
TI  - The importance of theory in cognitive behavior therapy: a perspective of
      contextual behavioral science.
AB  - For the past 30 years, generations of scholars of cognitive behavior therapy
      (CBT) have expressed concern that clinical practice has abandoned the close links
      with theory that characterized the earliest days of the field. There is also a
      widespread assumption that a greater working knowledge of theory will lead to
      better clinical outcomes, although there is currently very little hard evidence
      to support this claim. We suggest that the rise of so-called "third generation"
      models of CBT over the past decade, along with the dissemination of statistical
      innovations among psychotherapy researchers, have given new life to this old
      issue. We argue that theory likely does matter to clinical outcomes, and we
      outline the future research that would be needed to address this conjecture.

PMID- 24094784
TI  - The role of theory and research in the practice of cognitive-behavioral couple
      therapy: if you build it, they will come.
AB  - Cognitive-behavioral couple therapy (CBCT), while empirically validated and
      highly efficacious, does not always have positive results for couples. One factor
      that may limit the efficacy of this intervention is the way in which therapists
      are trained to provide this type of therapy. More specifically, there is a need
      for therapists to gain a solid foundation in CBCT theory in order to maximize
      treatment results. This paper presents an argument for why an understanding of
      theory is necessary for therapists in treating couples. Then, this paper presents
      our training model and how we integrate theory into our training of both graduate
      student therapists and more experienced clinicians. We take the stance that "if
      you build it, they will come." 

PMID- 24094785
TI  - Bridging the theory-practice gap by getting even bolder with the Boulder model.
AB  - Cognitive behavioral therapy is an effective treatment for virtually all
      psychiatric disorders. However, very few patients have access to it and few
      therapists are trained in the theory and practice of cognitive behavioral
      therapy. Based on the existing evidence and the articles of this series, the
      following recommendations are made: (a) all mental health care providers
      (including Psy.D. and social workers) need to be trained in the practice and
      theories of empirically supported treatments, specifically cognitive behavioral
      therapy; (b) clinical practice also needs to be based on theory, not just
      treatment manuals; and (c) psychological treatments have to move beyond the DSM
      boundaries. 

PMID- 24094786
TI  - Reflections on the theory-practice gap in cognitive behavior therapy.
AB  - The papers in this special series, edited by Pilecki and McKay (2013--this
      issue), are devoted to examining the theory-practice gap in cognitive-behavior
      therapy (CBT). A gap between theory and practice can occur at more than one
      level. First, there exists a substantial and concerning gap between the theories
      and interventions supported by research and those being offered to patients in
      the community (i.e., research-practice gap). There is also a growing concern in
      the field that the techniques and procedures that characterize cognitive
      behavioral therapies are becoming increasingly divorced from underlying theories
      (i.e., theory-procedure gap). In the present commentary we hope to summarize and
      comment on some of the themes, issues, and future directions raised by our
      contributors. 

PMID- 24094787
TI  - Computer-assisted therapies: examination of therapist-level barriers to their
      use.
AB  - Despite enthusiasm in the field for their potential ease of dissemination, little
      work has examined whether practicing clinicians are willing and able to use
      computer-assisted therapies (i.e., computerized treatments designed to be
      administered with therapist support). For therapists to use these tools, they
      require access to computer equipment, the skills needed to use the equipment, and
      willingness to adopt the technology in treatment. This study examined these three
      factors using survey data from a national sample of mental health clinicians
      (N=1,067). Respondents reported on their access to technology and computer
      fluency, in addition to completing the Computer-Assisted Therapy Attitudes Scale
      (CATAS), a measure of therapist attitudes designed for this study. Overall, the
      majority of therapists (90.7%) reported access to at least one computer at work
      and self-reported computer fluency levels were high. On average, therapists held
      positive attitudes towards computer-assisted therapies, although expressed
      concern that these technologies might damage rapport and did not feel that these
      technologies would improve treatment outcomes. Predictors of positive attitudes
      included greater general openness toward new treatments, greater comfort with
      computers, and easier access to technology at work (all ps<.01). Results
      suggested that, on the whole, therapists may be likely to integrate computer
      assisted therapies into their clinical practice. However, therapists vary both in
      their ability and willingness to use these tools. Implications for the
      dissemination of computer-assisted therapies are discussed. 

PMID- 24094788
TI  - Descriptive study of the Socratic method: evidence for verbal shaping.
AB  - In this study we analyzed 65 fragments of session recordings in which a cognitive
      behavioral therapist employed the Socratic method with her patients. Specialized
      coding instruments were used to categorize the verbal behavior of the
      psychologist and the patients. First the fragments were classified as more or
      less successful depending on the overall degree of concordance between the
      patient's verbal behavior and the therapeutic objectives. Then the fragments were
      submitted to sequential analysis so as to discover regularities linking the
      patient's verbal behavior and the therapist's responses to it. Important
      differences between the more and the less successful fragments involved the
      therapist's approval or disapproval of verbalizations that approximated
      therapeutic goals. These approvals and disapprovals were associated with
      increases and decreases, respectively, in the patient's behavior. These results
      are consistent with the existence, in this particular case, of a process of
      shaping through which the therapist modifies the patient's verbal behavior in the
      overall direction of his or her chosen therapeutic objectives. 

PMID- 24094789
TI  - A randomized open trial assessing the feasibility of behavioral activation for
      pathological grief responding.
AB  - This study investigated the feasibility of using behavioral activation to treat
      enduring postbereavement mental health difficulties using a two-arm, multiple
      baseline design comparing an immediate start group to a delayed start group at
      baseline, 12-, 24-, and 36-weeks postrandomization. Participants received 12-14
      sessions of behavioral activation within a 12-week intervention period starting
      immediately after the first assessment or after 12weeks for the delayed start
      group. Prolonged grief, posttraumatic stress, and depression symptoms were
      assessed as outcomes. Compared with no treatment, behavioral activation was
      associated with large reductions in prolonged, complicated, or traumatic grief;
      posttraumatic stress disorder; and depression symptoms in the intent-to-treat
      analyses. Seventy percent of the completer sample at posttreatment and 75 percent
      at follow-up responded to treatment with 45 percent at posttreatment and 40
      percent at follow-up being classified as evidencing high-end state functioning at
      12-week follow-up. 

PMID- 24094790
TI  - Development of a brief version of the Social Phobia Inventory using item response
      theory: the Mini-SPIN-R.
AB  - The Social Phobia Inventory (SPIN) is a widely used measure in mental health
      settings and a 3-item version (mini-SPIN) has been developed as a screening
      instrument for social anxiety disorder. In the present study, we examined the
      psychometric properties of the SPIN and developed a brief version (mini-SPIN-R)
      designed to assess social anxiety severity using item response theory. Our sample
      included 569 individuals with social anxiety disorder who participated in 2
      clinical trials and filled out a battery of self-report measures. Using a
      nonparametric kernel smoothing method we identified the most sensitive items of
      the SPIN. These 3 items comprised the mini-SPIN-R, which was found to have
      greater internal consistency, and to capture a greater range of symptoms compared
      to the mini-SPIN. The mini-SPIN-R evidenced superior convergent validity compared
      to the mini-SPIN and both measures had similar divergent validity. Thus, the mini
      SPIN-R is a promising brief measure of social anxiety severity. 

PMID- 24094791
TI  - A randomized trial of attention training for generalized social phobia: does
      attention training change social behavior?
AB  - The use of attention training protocols for the treatment of generalized social
      anxiety disorder (SAD) is undergoing increased examination. Initial
      investigations were positive but more recent investigations have been less
      supportive of the treatment paradigm. One significant limitation of current
      investigations is overreliance on self-report. In this investigation, we expanded
      on initial investigations by using a multimodal assessment of patient functioning
      (i.e., including behavioral assessment). Patients with a primary diagnosis of SAD
      (n=31) were randomly assigned to eight sessions of attention training (n=15) or
      placebo/control (n=16). Participants were assessed at pre- and posttreatment via
      self- and clinician-report of social anxiety as well as anxious and behavioral
      response to two in vivo social interactions. Results revealed no differences
      between groups at posttreatment for all study outcome variables, suggesting a
      lack of effect for the attention training condition. The results are concordant
      with recent investigations finding a lack of support for the use of attention
      training as an efficacious treatment for patients with SAD. 

PMID- 24094792
TI  - Reducing TV watching during adult obesity treatment: two pilot randomized
      controlled trials.
AB  - The more time adults spend being sedentary, the greater the risk of obesity. The
      effect of reducing television (TV) watching, a prominent sedentary behavior, on
      weight loss has not been tested in an adult standard behavioral obesity
      intervention, and the mechanisms by which reducing TV watching influences energy
      balance behaviors are not well understood. Two, 8-week, pilot, randomized
      controlled trials were conducted examining the effect of a reduced TV watching
      prescription on energy balance behaviors and weight loss within an adult standard
      behavioral obesity intervention. In the first study, participants (n=24) were
      randomized into one of two conditions: (a) reduce energy intake and increase
      moderate to vigorous physical activity (MVPA) (INCREASE PA); or (b) reduce energy
      intake and decrease TV watching (DECREASE TV). As findings from the first pilot
      study did not show an increase in MVPA in the DECREASE TV group, the second study
      was designed to examine the effect of adding a reduced TV prescription to a
      standard intervention to optimize outcomes. In Pilot Study 2, participants (n=28)
      were randomized to INCREASE PA or to INCREASE PA+DECREASE TV. Outcomes included
      objectively measured TV watching and MVPA, self-reported light physical activity
      (LPA-Pilot Study 2 only), self-reported dietary intake while watching TV, and
      weight. Conditions with TV watching prescriptions significantly reduced TV
      watching. Both studies showed medium to large effect sizes for conditions with TV
      watching prescriptions to show greater reductions in dietary intake while
      watching TV. Pilot Study 1 found a trend for an increase in MVPA in INCREASE PA
      and Pilot Study 2 found significant increases in MVPA in both conditions. Pilot
      Study 2 found a significant increase in LPA in the INCREASE PA+DECREASE TV.
      Results indicate adding a TV watching prescription to a standard obesity
      intervention did not enhance increases in MVPA, but may assist with reducing
      dietary intake while TV watching and increasing LPA. Future research should
      examine the effect of reducing TV watching during obesity treatment over a longer
      time frame in a larger sample. 

PMID- 24094793
TI  - Couple relationship distress and observed expression of intimacy during
      reminiscence about positive relationship events.
AB  - Satisfied couples report that positive, intimate communication is central to
      their relationship. We developed the positive reminiscence task, in which couples
      discuss positive relationship moments to assess communication of positive
      intimacy. The behavior and heart rate of 28 satisfied and 25 distressed couples
      were assessed during positive reminiscence and problem solving. As predicted,
      satisfied couples demonstrated higher rates of positive affect and dyadic
      intimacy than distressed couples during positive reminiscence, and these positive
      behaviors occurred at much lower rates during problem solving than positive
      reminiscence. However, the differences between distressed and satisfied couples
      were more marked on most assessed behaviors during problem solving rather than
      positive reminiscence. Two notable exceptions were that dyadic intimacy and
      sadness differed more between distressed and satisfied couples during positive
      reminiscence than problem solving. The positive reminiscence task assesses
      intimate behaviors in a manner likely to be useful in research and practice. 

PMID- 24094794
TI  - Mental imagery and post-event processing in anticipation of a speech performance
      among socially anxious individuals.
AB  - The present study investigated whether post-event processing (PEP) involving
      mental imagery about a past speech is particularly detrimental for socially
      anxious individuals who are currently anticipating giving a speech. One hundred
      fourteen high and low socially anxious participants were told they would give a 5
      min impromptu speech at the end of the experimental session. They were randomly
      assigned to one of three manipulation conditions: post-event processing about a
      past speech incorporating imagery (PEP-Imagery), semantic post-event processing
      about a past speech (PEP-Semantic), or a control condition, (n=19 per
      experimental group, per condition [high vs low socially anxious]). After the
      condition inductions, individuals' anxiety, their predictions of performance in
      the anticipated speech, and their interpretations of other ambiguous social
      events were measured. Consistent with predictions, high socially anxious
      individuals in the PEP-Imagery condition displayed greater anxiety than
      individuals in the other conditions immediately following the induction and
      before the anticipated speech task. They also interpreted ambiguous social
      scenarios in a more socially anxious manner than socially anxious individuals in
      the control condition. High socially anxious individuals made more negative
      predictions about their upcoming speech performance than low anxious participants
      in all conditions. The impact of imagery during post-event processing in social
      anxiety and its implications are discussed.

PMID- 24094795
TI  - Treating PTSD in patients with psychosis: a within-group controlled feasibility
      study examining the efficacy and safety of evidence-based PE and EMDR protocols.
AB  - The present study uses a within-group controlled design to examine the efficacy
      and safety of two psychological approaches to posttraumatic stress disorder
      (PTSD) in 10 patients with a concurrent psychotic disorder. Patients were
      randomly assigned either to prolonged exposure (PE; N=5) or eye movement
      desensitization and reprocessing (EMDR; N=5). Before, during, and after
      treatment, a total of 20 weekly assessments of PTSD symptoms, hallucinations, and
      delusions were carried out. Twelve weekly assessments of adverse events took
      place during the treatment phase. PTSD diagnosis, level of social functioning,
      psychosis-prone thinking, and general psychopathology were assessed pretreatment,
      posttreatment, and at three-month follow-up. Throughout the treatment, adverse
      events were monitored at each session. An intention-to-treat analysis of the 10
      patients starting treatment showed that the PTSD treatment protocols of PE and
      EMDR significantly reduced PTSD symptom severity; PE and EMDR were equally
      effective and safe. Eight of the 10 patients completed the full intervention
      period. Seven of the 10 patients (70%) no longer met the diagnostic criteria for
      PTSD at follow-up. No serious adverse events occurred, nor did patients show any
      worsening of hallucinations, delusions, psychosis proneness, general
      psychopathology, or social functioning. The results of this feasibility trial
      suggest that PTSD patients with comorbid psychotic disorders benefit from trauma
      focused treatment approaches such as PE and EMDR. 

PMID- 24094796
TI  - Ripples of consciousness.
AB  - Casali et al. recently showed that the complexity of the electrophysiological
      brain response to a transcranial magnetic stimulation pulse distinguishes
      conscious from unconscious humans in a variety of conditions. In addition to its
      theoretical implications, this novel method paves the way to a quantitative
      assessment of the states of consciousness. 

PMID- 24094797
TI  - Complex relationships between structural and functional brain connectivity.
AB  - In recent work, O'Reilly and colleagues demonstrate relatively intact
      interhemispheric functional connectivity in a macaque brain in the absence of
      major commissural fibers. This work adds to a growing body of literature
      challenging the notion that structural and functional brain connectivity metrics
      are related in a straightforward manner. 

PMID- 24094798
TI  - Objective measures of laryngeal imaging: what have we learned since Dr. Paul
      Moore.
AB  - Dr. Paul Moore pioneered the use of high-speed cinematography for observation of
      normal and abnormal vocal fold vibrations during phonation. His analysis of the
      glottal area waveform, opening and closing speed index, and open quotient from
      the high-speed films were labor intensive but relevant today. With advances in
      digital image capture and automated image extraction techniques, stroboscopy and
      high-speed images of vocal fold vibration may be analyzed with objective
      measures. Digital high-speed image capture in color is now clinically practical
      at high resolution. Digital kymography now allows analysis of the vibratory
      waveform from each vocal fold. Serial capture and comparison can document changes
      in vibratory function with treatment. Quantification of vocal fold vibration
      using such techniques is now practical. This is a review of vocal fold vibration
      capture and analysis techniques since Dr. Moore. 

PMID- 24094799
TI  - Intonation and gender perception: applications for transgender speakers.
AB  - Intonation is commonly addressed in voice and communication feminization therapy,
      yet empirical evidence of gender differences for intonation is scarce and rarely
      do studies examine how it relates to gender perception of transgender speakers.
      This study examined intonation of 12 males, 12 females, six female-to-male, and
      14 male-to-female transgender speakers describing a Norman Rockwell image.
      Several intonation measures were compared between biological gender groups,
      between perceived gender groups, and between male-to-female (MTF) speakers who
      were perceived as male, female, or ambiguous gender. Speakers with a larger
      percentage of utterances with upward intonation and a larger utterance semitone
      range were perceived as female by listeners, despite no significant differences
      between the actual intonation of the four gender groups. MTF speakers who do not
      pass as female appear to use less upward and more downward intonations than
      female and passing MTF speakers. Intonation has potential for use in transgender
      communication therapy because it can influence perception to some degree. 

PMID- 24094800
TI  - Validation of the Italian Voice Handicap Index-10.
AB  - OBJECTIVE: Time consuming is an important aspect in assessing dysphonic patients.
      So, the English version of the Voice Handicap Index (VHI-30), a self-administered
      questionnaire consisting of 30 items used to evaluate patients' self-perception
      of voice problems, was reduced to 10 items (VHI-10) for clinical purposes. In
      2010, an Italian version of VHI-30 was validated, now the aims of this study were
      to analyze the psychometric properties of an Italian version of VHI-10 and to
      evaluate its validity in a cohort of patients affected by organic or functional
      dysphonia. STUDY DESIGN: Cross-sectional study. METHODS: The Italian version of
      the VHI-30 was submitted to 372 dysphonic participants and 120 healthy control
      subjects and was conducted again 2 weeks later. The 10 items constituting the VHI
      10 were extracted from the VHI-30. For 73 dysphonic patients, the questionnaire
      was also administered after treatment. RESULTS: The scores of the control group
      were significantly lower with respect to all diagnostic subgroups (P<0.001). The
      Cronbach's alpha, test-retest, and Pearson's correlation index demonstrated high
      reliability and validity of the Italian VHI-10. The ratio of the VHI-10 and VHI
      30 scores was higher than 0.333 in all subgroups. CONCLUSION: This study
      demonstrated that the Italian VHI-10 is a robust tool that can adequately
      represent and replace the VHI-30. The reported results support the use of the VHI
      10 for the Italian population in clinical settings owing to its validity and
      rapid and simple use.

PMID- 24094801
TI  - The effects of stress on singing voice accuracy.
AB  - OBJECTIVE: The quality of a music performance can be lessened or enhanced if the
      performer experiences stressful conditions. In addition, the quality of a sung
      performance requires control of the fundamental frequency of the voice, which is
      particularly sensitive to stress. The present study aimed to clarify the effects
      of stress on singing voice accuracy. METHODS: Thirty-one music students were
      recorded in a stressful condition (ie, a music examination) and a nonstressful
      condition. Two groups were defined according to the challenge level of the music
      examination (first and second music levels). Measurements were made by self
      reported state anxiety (CSAI-2R questionnaire) and by observing heart rate
      activity (electrocardiogram) during each performance. In addition, the vocal
      accuracy of the sung performances was objectively analyzed. RESULTS: As expected,
      state anxiety and heart rate were significantly higher on the day of the music
      examination than in the nonstressful condition for all the music students.
      However, the effect of stress was positive for the first-year students but
      negative for the second-year students, for whom the music examination was
      particularly challenging. In addition, highly significant correlations were found
      between the intensity of cognitive symptoms and the vocal accuracy criteria.
      DISCUSSION: This study highlights the contrasting effects of stress on singing
      voice accuracy but also the need to consider the challenge level and perception
      of the symptoms in experimental and pedagogical settings.

PMID- 24094802
TI  - Acoustic investigation of stress patterns in Parkinson's disease.
AB  - OBJECTIVES: Although reduced stress is thought to be one of the most deviant
      speech dimensions in hypokinetic dysarthria associated with Parkinson's disease
      (PD), the mechanisms of stress production in PD have not been thoroughly explored
      by objective methods. The aim of the present study was to quantify the effect of
      PD on prosodic characteristics and to describe contrastive stress patterns in
      parkinsonian speech. METHODS: The ability of 20 male speakers with early PD and
      16 age- and gender-matched healthy controls (HCs) to signal contrastive stress
      was investigated. Each participant was instructed to unnaturally emphasize five
      key words while reading a short block of text. Acoustic analyses were based on
      the measurement of pitch, intensity, and duration. In addition, an innovative
      measurement termed the stress pattern index (SPI) was designed to mirror the
      effect of all distinct acoustic cues exploited during stress production. RESULTS:
      Although PD patients demonstrated a reduced ability to convey contrastive stress,
      they could still notably increase pitch, intensity, and duration to emphasize a
      word within a sentence. No differences were revealed between PD and HC stress
      productions using the measurements of pitch, intensity, duration, and intensity
      range. However, restricted SPI and pitch range were evident in the PD group.
      CONCLUSIONS: A reduced ability to express stress seems to be the distinctive
      pattern of hypokinetic dysarthria, even in the early stages of PD. Because PD
      patients were able to consciously improve their speech performance using multiple
      acoustic cues, the introduction of speech therapy may be rewarding.

PMID- 24094803
TI  - Laryngeal chondrosarcoma of the arytenoid cartilage presenting as bilateral vocal
      fold immobility: a case report and literature review.
AB  - OBJECTIVES: To describe an atypical case of laryngeal chondrosarcoma of arytenoid
      cartilage presenting as bilateral vocal fold immobility and to avoid potential
      missed diagnosis. METHODS: Our case study included a detail history, physical and
      radiological examination, laryngeal electromyography (LEMG), and surgical
      treatment and pathology analysis. We compared it with the previously discussed
      cases of chondrosarcoma of arytenoid cartilage in the literature. RESULTS:
      Chondrosarcomas of the arytenoid cartilage is rare, and to date only
      approximately 10 cases have been reported. We reported a case of a 51-year-old
      man with 1 month of persistent dyspnea presenting with bilateral vocal fold
      immobility without neoplasms in larynx. The LEMG showed no obvious abnormality.
      The cervical-enhanced computed tomography (CT) found no significant signs of a
      mass except for localized high-density areas in arytenoid cartilage. Right
      arytenoidectomy and biopsy were performed under general anesthesia with CO2 laser
      with the pathological diagnosis of chondroma. A total laryngectomy was performed
      2 years later, and low-grade chondrosarcoma was the final diagnosis. CONCLUSIONS:
      Laryngeal chondrosarcomas of the arytenoid cartilage are rare. It is easily
      neglected, especially in those cases presenting with idiopathic vocal fold
      immobility without any obvious signs of neoplasms. The LEMG and laryngeal CT are
      necessary. Sometimes, a biopsy of the arytenoid cartilage is essential.

PMID- 24094804
TI  - Relationship between radiotherapy and gastroesophageal reflux disease in causing
      tracheoesophageal voice rehabilitation failure.
AB  - OBJECTIVE: The objective was to analyze the association of radiotherapy with
      gastroesophageal reflux as determinant of fistula related pathology, in voice
      prosthesis patients. STUDY DESIGN: Retrospective study. METHODS: Sixty-one
      laryngectomy patients were enrolled between 2005 and 2012. All patients underwent
      phonatory rehabilitation with voice prosthesis, along with evidence of
      gastroesophageal reflux disease, for which proton pump inhibitors (PPIs) were
      prescribed. We analyzed the occurrence of fistula-related problems among patients
      who received postoperative radiotherapy and those patients who did not. RESULTS:
      We observed a higher rate of failure of speech rehabilitation in laryngectomy
      patients with gastroesphageal reflux: this occurred when they had a history of
      postoperative radiotherapy (45%) compared with patients who did not (17%) (P <
      0.05), although all patients were treated with PPIs. CONCLUSION: Our results seem
      to confirm the importance of postoperative radiotherapy with gastroesophageal
      reflux for the determinism of fistula-related problems.

PMID- 24094805
TI  - An unusual cause of congestive heart failure in a young woman.
AB  - BACKGROUND: Congestive heart failure (CHF) is a common Emergency Department (ED)
      disorder that accounts for >5 million ED visits annually. Although quite rare,
      patent ductus arteriosus (PDA) is a serious cause of CHF that if left untreated
      can lead to life-threatening sequelae, such as hypertensive pulmonary vascular
      disease, endarteritis, and aneurysms of the ductus. OBJECTIVE: To discuss a case
      of PDA leading to CHF that illustrates one of the common complications of
      untreated PDA. CASE REPORT: A 35-year-old woman presented to the ED with a 2
      month history of shortness of breath, dyspnea on exertion, decreased exercise
      tolerance, and orthopnea. The physical examination revealed a 4/6 continuous
      machine-like murmur. In the presence of new CHF and an atypical murmur, a
      transthoracic echocardiogram was performed that confirmed the diagnosis of PDA.
      She underwent an uncomplicated percutaneous closure of the ductus with
      significant improvement in her symptoms. CONCLUSIONS: Persistent PDA in adulthood
      is a rare but important cause of CHF with significant morbidity and mortality if
      not appropriately diagnosed and treated.

PMID- 24094806
TI  - Primary angioplasty in patient with ST-segment elevation myocardial infarction in
      the setting of intentional carbon monoxide poisoning.
AB  - BACKGROUND: ST-segment elevation myocardial infarction (STEMI) due to coronary
      artery occlusion in the setting of acute carbon monoxide (CO) poisoning is a very
      rare presentation. OBJECTIVE: Our aim was to report on the use of primary
      angioplasty in a patient with STEMI in the setting of CO poisoning. CASE REPORT:
      A 36-year-old man with retrosternal chest pain was admitted after exposure to CO.
      The initial electrocardiogram (ECG) showed ST depression in I, aVL, and V3-V4
      with slight ST elevation in II, III, aVF leads. Toxic carboxyhemoglobin level of
      22% and troponin I of 2.19 MUg/L were confirmed. After oxygen therapy the chest
      pain diminished, but after about 15 h it returned. The repeat ECG revealed
      normalization of previous ST depression with persistent ST elevation in II, III,
      aVF leads. The troponin I concentration was 5.94 MUg/L. An echocardiogram
      demonstrated an apex hypokinesia involving the adjacent segments of the anterior
      and lateral wall. On the coronary angiogram, an acute occlusion of the distal
      left anterior descending coronary artery was confirmed. Primary percutaneous
      coronary intervention (PCI) of the infarct-related artery was performed. After
      PCI, the patient was symptom free and had partial ST-segment elevation
      resolution. The patient was discharged home after 7 days, with persistent ST-T
      changes and mild hypokinesia of the apex suggesting myocardial injury.
      CONCLUSIONS: Patients with toxic CO exposure who have symptoms of STEMI should be
      carefully evaluated with serial ECG, cardiac necrosis marker measurements, and an
      echocardiogram. When there is evidence of myocardial injury, a wider use of
      coronary angiography can identify patients who could benefit from PCI.

PMID- 24094807
TI  - Modes of cell wall growth differentiation in rod-shaped bacteria.
AB  - A bacterial cell takes on the challenge to preserve and reproduce its shape at
      every generation against a substantial internal pressure by surrounding itself
      with a mechanical support, a peptidoglycan cell wall. The enlargement of the cell
      wall via net incorporation of precursors into the pre-existing wall conditions
      bacterial growth and morphology. However, generation, reproduction and/or
      modification of a specific shape requires that the incorporation takes place at
      precise locations for a defined time period. Much has been learnt in the past few
      years about the biochemistry of the peptidoglycan synthesis process, but
      topological approaches to the understanding of shape generation have been
      hindered by a lack of appropriate techniques. Recent technological advances are
      paving the way for substantial progress in understanding the mechanisms of
      bacterial morphogenesis. Here we review the latest developments, focusing on the
      impact of new techniques on the precise mapping of cell wall growth sites. 

PMID- 24094808
TI  - Do the divisome and elongasome share a common evolutionary past?
AB  - The divisome and elongasome are bacterial protein complexes responsible for
      peptidoglycan (PG) synthesis during cell division and elongation, respectively.
      We review several lines of evidence, arguing for a shared evolutionary past of
      the divisome and elongasome. Both integrate closely related penicillin-binding
      proteins (PBPs) for PG synthesis, use proteins of the RodA/FtsW (SEDS, shape,
      elongation, division and sporulation) family for Lipid II export and interact
      with MraY/Mur proteins for Lipid II synthesis. It was recently shown that the
      actin-like protein FtsA of the divisome polymerises on membranes, adding another
      parallel, since membrane-associated filaments of the bacterial actin MreB guide
      the elongasome. Given these similarities, it seems plausible to conclude that the
      elongasome is a modified version of the divisome, without the membrane
      constricting FtsZ-ring and its associated machinery on the inside. 

PMID- 24094809
TI  - Iron uptake and virulence in Histoplasma capsulatum.
AB  - Histoplasma capsulatum (Hc) is the causative organism of a spectrum of disease
      affecting both the immunocompetent and the immunocompromised host. Hc is a
      dimporhic fungus that converts from conidia to the pathogenic yeast phase after
      entry into the mammalian host. Despite rapid ingestion by macrophages, it
      survives intracellularly within the macrophage. The intracellular survival
      strategy of Hc yeasts focuses on regulating the phagosomal compartment by
      modulating the intraphagosomal pH to 6.5. As an intracellular pathogen of MPhi,
      Hc obtains iron from Fe-transferrin, ferritin, or both, via the production of
      hydroxamate siderophores, and the production of ferric reductases. A better
      understanding of the mechanisms by which Hc yeasts acquire iron from the host may
      lead to novel therapeutics for histoplasmosis. 

PMID- 24094810
TI  - Brugada-type patterns are easily observed in high precordial lead ECGs in
      collegiate athletes.
AB  - BACKGROUND: Displacement of ECG leads can result in unwarranted findings. We
      assessed the frequency of Brugada-type patterns in athletes when precordial leads
      were purposely placed upward. METHODS: Four hundred ninety-one collegiate
      athletes underwent two ECGs: one with standard leads, one with V1 and V2 along
      the 2nd intercostal space. A positive Brugada-type pattern was defined as ST
      elevation in V1 or V2 consistent with a Type 1, 2, or 3 pattern in the high-lead
      ECG. A control group was comprised of 181 outpatients. RESULTS: No Type 1
      patterns were seen. In 58 athletes (11.8%), a Brugada-type 2 or 3 pattern was
      observed. Those with Brugada-type 2 or 3 patterns were more likely male, taller,
      and heavier. In the control group, 18 (9.9%) had Brugada-type 2 or 3 patterns and
      were more likely male. CONCLUSIONS: Proper lead positioning is essential to avoid
      unwarranted diagnosis of a Brugada-type ECG, especially in taller, heavier male
      athletes.

PMID- 24094811
TI  - Assessment of pulmonary artery pulse wave velocity in children: an MRI pilot
      study.
AB  - PURPOSE: To assess the feasibility of measuring pulmonary artery (PA) pulse wave
      velocity (PWV) in children breathing ambient air and 12% oxygen. METHODS:
      Velocity-encoded phase-contrast MR images of the PA were acquired in 15 children,
      aged 9-12years, without evidence of cardiac or pulmonary diseases. PWV was
      derived as the ratio of flow to area changes during early systole. Each child was
      scanned twice, in air and after at least 20minutes into inspiratory hypoxic
      challenge. Intra-observer and inter-observer variability and repeatability were
      also compared. RESULTS: PA PWV, which was successfully measured in all subjects,
      increased from 1.31+/-0.32m/s in air to 1.61+/-0.58m/s under hypoxic challenge
      (p=0.03). Intra- and inter-observer coefficients of variations were 9.0% and
      15.6% respectively. Good correlation within and between observers of r=0.92 and
      r=0.72 respectively was noted for PA PWV measurements. Mean (95% limit of
      agreement) intra- and inter-observer agreement on Bland-Altman analysis were 
      0.02m/s (-0.41-0.38m/s) and -0.28m/s (-1.06-0.49m/s). CONCLUSION: PA PWV
      measurement in children using velocity-encoded MRI is feasible, reproducible and
      sufficiently sensitive to detect differences in PA compliance between normoxia
      and hypoxia. This technique can be used to detect early changes of PA compliance
      and monitor PAH in children.

PMID- 24094812
TI  - Glutamine sensitivity analysis identifies the xCT antiporter as a common triple
      negative breast tumor therapeutic target.
AB  - A handful of tumor-derived cell lines form the mainstay of cancer therapeutic
      development, yielding drugs with an impact typically measured as months to
      disease progression. To develop more effective breast cancer therapeutics and
      more readily understand their clinical impact, we constructed a functional
      metabolic portrait of 46 independently derived breast cell lines. Our analysis of
      glutamine uptake and dependence identified a subset of triple-negative samples
      that are glutamine auxotrophs. Ambient glutamine indirectly supports
      environmental cystine acquisition via the xCT antiporter, which is expressed on
      one-third of triple-negative tumors in vivo. xCT inhibition with the clinically
      approved anti-inflammatory sulfasalazine decreases tumor growth, revealing a
      therapeutic target in breast tumors of poorest prognosis and a lead compound for
      rapid, effective drug development.

PMID- 24094813
TI  - Accuracy of predictive equations for the measurement of resting energy
      expenditure in older subjects.
AB  - BACKGROUND AND AIMS: The measurement of resting energy expenditure (REE) is
      important to assess individual total energy requirements in older subjects. The
      validity of REE prediction equations in this population has not been thoroughly
      evaluated and therefore the main aim of this analysis was to assess the accuracy
      of REE prediction equations in older subjects. METHODS: Weight, height and body
      mass index (BMI) were measured. REE was measured by indirect calorimetry (IC) in
      68 older subjects (age: 60-94 years, M/F: 13/55, BMI: 26.3 +/- 5.0 kg/m(2)).
      Measured REE was compared to 14 equations for the calculation of REE estimates.
      In addition, two novel approaches (Aggregate model and meta-regression equations)
      for the prediction of REE were evaluated. Paired t test and Bland-Altman method
      were used to assess the agreement of the equations. RESULTS: The average measured
      REE was 1298 +/- 264 kcal/day. The equation with the smallest bias was proposed
      by Muller (Bias +/- 2SD = +3 +/- 294 kcal/day) whereas the Mifflin equation was
      associated with the largest error (Bias +/- 2SD = -172 +/- 282 kcal/day). The
      Aggregate, Muller, Harris-Benedict and Fredrix equations were characterised by a
      prediction within +/-10% of measured REE in more than 60% of subjects. Of the
      four algorithms, only the Aggregate equation did not show a significant
      association of the measurement bias with age, BMI and gender. CONCLUSIONS: The
      Aggregate algorithm was characterised by a higher, overall accuracy for the
      prediction of REE in older subjects and its use should be advocated in older
      subjects. However, due to the large variability of the estimates, the measurement
      of REE by IC is still recommended for an accurate assessment of individual REE.

PMID- 24094815
TI  - Scientific Globish: clear enough is good enough.
AB  - Writing in English is a major problem for many scientists. One radical solution
      would be the adoption by the scientific community of a simplified, standardised
      version of English that would be easy to learn, use, and understand, and that
      would increase the clarity, precision, and accuracy of scientific texts. 

PMID- 24094814
TI  - The nutritional strategy: four questions predict morbidity, mortality and health
      care costs.
AB  - BACKGROUND: Nutritional care for hospital in-patients is potentially important
      but challenging. OBJECTIVE: To investigate the association between nutritional
      status and clinical outcomes. METHODS: Eight prevalence surveys were performed at
      Haukeland University Hospital, Norway, during 2008-2009. In total 3279 patients
      were classified as being at nutritional risk or not according to the Nutritional
      Risk Screening (NRS 2002) tool. The initial four questions of NRS 2002 assess
      dietary intake, weight loss, body mass index (BMI) and illness severity. RESULTS:
      The overall prevalence of nutritional risk was 29%. Adjusted mean days for
      hospitalisation was 8.3 days for patients at nutritional risk and 5.0 days for
      patients not at risk (p < 0.001). In adjusted models, patients at nutritional
      risk had increased one-year mortality (OR 4.07, 95% CI 2.90-5.70), morbidity (OR
      1.59, 95% CI 1.18-2.13), and were 1.24 (95% CI 1.16-1.32) times more likely to
      have had a new admission during the three previous years and the one subsequent
      year, compared to patients not at risk. A 'positive' response to the initial four
      questions was associated with increased risk of morbidity and mortality. Patients
      with a reduced dietary intake during the last weeks had OR 1.72 (95% CI 1.03
      2.85) for one-year mortality. Patients with a positive answer on all the initial
      four questions had ten times increased risk for mortality the following year, OR
      13.0 (95% CI 4.52-37.6). CONCLUSION: The four initial questions of the NRS 2002
      robustly identify nutritional risk and were strong predictors of hospitalisation,
      morbidity and most importantly mortality among hospitalised patients. Thus, these
      simpler and short questions are robust indicators for subsequent poor outcomes.

PMID- 24094816
TI  - Hit-to-lead optimization of 2-(1H-pyrazol-1-yl)-thiazole derivatives as a novel
      class of EP1 receptor antagonists.
AB  - We describe a medicinal chemistry approach to generate a series of 2-(1H-pyrazol
      1-yl)thiazole compounds that act as selective EP1 receptor antagonists. The
      obtained results suggest that compound 12 provides the best EP1 receptor
      antagonist activity and demonstrates good oral pharmacokinetics. 

PMID- 24094818
TI  - 6-(4-Pyridyl)pyrimidin-4(3H)-ones as CNS penetrant glycogen synthase kinase-3beta
      inhibitors.
AB  - The discovery of a series of 6-(4-pyridyl)pyrimidin-4(3H)-ones derived from a hit
      compound with low molecular weight and sufficient chemical space is reported.
      Transformation of substituents led to subnanomolar potent inhibitors with in vivo
      tau phoshorylation lowering activity. 

PMID- 24094819
TI  - Color naming of colored non-color words and the response-exclusion hypothesis: a
      comment on Mahon et al. and on Roelofs and Piai.

PMID- 24094817
TI  - Modular assembly of dimeric HIV fusion inhibitor peptides with enhanced antiviral
      potency.
AB  - The HIV-1 envelope gp120/gp41 glycoprotein complex plays a critical role in virus
      host cell membrane fusion and has been a focus for the development of HIV fusion
      inhibitors. In this Letter, we present the synthesis of dimers of HIV fusion
      inhibitor peptides C37H6 and CP32M, which target the trimeric gp41 in the pre
      hairpin intermediate state to inhibit membrane fusion. Reactive peptide modules
      were synthesized using native chemical ligation and then assembled into dimers
      with varying linker lengths using Cu(I)-catalyzed azide-alkyne cycloaddition
      (CuAAC) 'click' chemistry. Cell-cell fusion inhibition assays demonstrated that
      dimers with a (PEG)7 linker showed enhanced antiviral potency over the
      corresponding monomers. Moreover, the bio-orthogonal nature of the CuAAC 'click'
      reaction provides a practical way to assemble heterodimers of HIV fusion
      inhibitors. Heterodimers consisting of the T20-sensitive strain inhibitor C37H6
      and the T20-resistant strain inhibitor CP32M were produced that may have broader
      spectrum activities against both T20-sensitive and T20-resistant strains. 

PMID- 24094820
TI  - An ethnographical study on the academic experiences of Chinese male nursing
      students.
AB  - Because there have been very few recent studies focusing on the nursing studies
      of Chinese male learners in Hong Kong, this paper reports some findings on the
      educational experiences of such students from a local university, giving them a
      chance to voice out their concerns and express their feelings. In this
      qualitative ethnographical study, 18 second- to fourth-year male nursing students
      were recruited by purposive snowball sampling and invited to participate in
      individual semi-structured interviews for the collecting of data. The taped
      recordings were transcribed and translated. Following this, five themes were
      identified for content analysis. The findings of this study suggest that people
      would be more likely to accept male nurses; and male nursing students would be
      more able see their role as nurses with the acceptance of some feminine subjects
      in the nursing curriculum. This study provided male nursing students the chance
      to express their thoughts and experiences on nursing education, which will
      suggest further modifications to the curriculum design and implementation. 

PMID- 24094821
TI  - Hysterectomy in Denmark 1977-2011: changes in rate, indications, and
      hospitalization.
AB  - OBJECTIVE: To describe conditions regarding hysterectomy for benign indications
      during the past 35 years in Denmark. STUDY DESIGN: Population-based register
      study of 167,802 women who underwent hysterectomy for benign conditions in the
      period 1977-2011. Patient data regarding operative techniques, hospitalization,
      indications, patient age, and geography were extracted from the Danish National
      Patient Register. RESULTS: The overall rate of hysterectomy was around
      180/100,000 woman years during the period. A rise in laparoscopic and vaginal
      hysterectomy was seen at the expense of abdominal hysterectomy. The indication of
      pelvic organ prolapse and abnormal uterine bleeding increased while the
      indication of fibroids decreased. The average age of women at time of
      hysterectomy increased from 46 years in 1977-1981 to 50 years in 2006-2011. The
      mean number of hospitalization days was reduced by 75%. Regional differences were
      detected regarding route of hysterectomy and hospitalization. CONCLUSIONS: This
      study demonstrates a change in the pattern of indications for hysterectomy,
      increased age of the affected women, reduced length of stay in the hospital, and
      a rise in the percentage of minimal invasive surgical procedures.

PMID- 24094822
TI  - Social disparity affects the incidence of placental abruption among multiparous
      but not nulliparous women: a register-based analysis of 1,162,126 singleton
      births.
AB  - OBJECTIVES: To identify risk factors for placental abruption and to evaluate
      associations between adverse perinatal outcomes and placental abruption
      stratified by parity among women with singleton births from 1991 to 2010 in
      Finland. STUDY DESIGN: A retrospective population-based case-control study of
      singleton births in Finland from 1991 to 2010 (n=1,162,126 from the Finnish
      Medical Birth Register). We modelled the group-specific risk factors for
      placental abruption in unadjusted and adjusted models. RESULTS: In total 3.5 and
      3.7 per 1000 nulliparous and multiparous women, respectively, were affected by
      placental abruption. The recurrence rate was 8.6 per 1000 births. The adjusted
      risk for placental abruption increased in pregnancies characterised by advanced
      maternal age, low birth weight, smoking, major congenital anomaly, preeclampsia
      and male foetal sex in both parity groups. In vitro fertilisation increased the
      risk only in nulliparae whereas anaemia, a prior caesarean section and the lowest
      socioeconomic status increased the risk in multiparae. Births affected by
      placental abruption were associated with an increased admission for neonatal
      intensive care, preterm birth, low birth weight (<2500 g), small for gestational
      age infants, low Apgar scores, and low newborn umbilical vein pH (<7.15).
      Placental abruption resulted in increased risks of stillbirth and early neonatal
      death in both parity groups. CONCLUSIONS: The burden of placental abruption is
      equal in nulliparae and multiparae, but risk factors vary substantially. Social
      disparity only affects the incidence of placental abruption among multiparous
      women, indicating that factors related to lifestyle and health behaviour have
      different effects on the parity groups.

PMID- 24094823
TI  - A pH-sensitive gene delivery system based on folic acid-PEG-chitosan - PAMAM
      plasmid DNA complexes for cancer cell targeting.
AB  - In this study, pH-sensitive biomaterials coated polymer/DNA nanocomplexes
      containing a high mobility group box 1 (HMGB1) were developed as an efficient non
      viral gene delivery system. HMGB1 is a family of endogenous molecules that
      contains nuclear locating sequences (NSL). Polyethylene glycol tethered
      carboxylated chitosan modified with folic acid (FA-PEG-CCTS) was synthesized and
      its buffering capacity was determined by acid-base titration. A pH-sensitive core
      shell system FA-PEG-CCTS/PAMAM/HMGB1/pDNA nanocomplexes (FPCPHDs), was prepared
      and characterized. Electrophoresis showed that FPCPHDs were resistant to heparin
      replacement and DNase I digestion. FPCPHDs exhibited only minor toxic effects on
      HepG2 and KB cells. The results of both luciferase activity assay and RFP
      fluorescence intensity analysis showed that FPCPHDs enhanced gene transfection
      and expression in KB cells. Moreover, gene transfection and expression in KB
      cells were inhibited by free folic acid. Intracellular trafficking of FPCPHDs in
      KB cells showed that FPCPHDs could rapidly escape from endo-lysosomes and become
      exclusively located in the nucleus at 3 h post transfection. In addition, FPCPHDs
      exhibited increased red fluorescence protein (RFP) expression at the tumor site
      of S180 xenograft nude mice. All results suggest that FPCPHDs is an efficient
      approach to improve the transfection and expression efficiency in most FR
      positive cancer cells.

PMID- 24094824
TI  - Dental composite materials containing carolacton inhibit biofilm growth of
      Streptococcus mutans.
AB  - OBJECTIVE: Caries adjacent to restorations is one of the main causes for
      restoration replacement. Antimicrobial substances incorporated into dental
      materials would potentially be able to reduce secondary caries initiation and
      progression. This study investigated biofilm growth of Streptococcus mutans UA159
      on the surface of composite materials containing the biomolecule carolacton
      compared to materials containing chlorhexidine (CHX) and triclosan. METHODS:
      Biofilm inhibition was investigated by counting colony forming units (CFU),
      viability staining (Life/Dead), and real-time quantitative PCR. RESULTS: First,
      the antimicrobial substances were added to the cultivation medium at 2.5 MUg/ml
      (0.0002%) and 0.25 MUg/ml (0.00002%). CHX eliminated bacterial growth and biofilm
      formation completely. Triclosan was effective at 2.5 MUg/ml, but at 0.25 MUg/ml
      biofilm mass and viability were unchanged, yet the number of CFU increased due to
      disruption of cell chains and biofilm aggregates. Carolacton had a limited effect
      on biofilm growth and mass, but reduced viability significantly. When
      incorporated into composite materials carolacton (25 MUg/ml resp. 0.002%, w/w)
      had no adverse effect on physical/mechanical properties and retained its biofilm
      inhibiting effect. Life/Dead staining revealed a reduction of biofilm viability
      of up to 64%. CFUs were reduced by 98% and qPCR demonstrated a mean inhibition of
      87%. In contrast, materials containing CHX or triclosan showed an insignificant
      effect on biofilm formation, even at a 100 fold increased concentration (0.2%).
      The anti-biofilm activity of composite material containing carolacton was stable
      over a period of 42 days. SIGNIFICANCE: Carolacton incorporated into dental
      filling material has a strong biofilm-inhibiting effect on S. mutans and is
      therefore potentially able to prevent secondary caries formation.

PMID- 24094825
TI  - Broadband noise suppression and feature identification of ECG waveforms using
      mathematical morphology and embedding theorem.
AB  - The paper presents an adaptive morphological filter developed using multiscale
      mathematical morphology (MM) to reject broadband noise from ECG signals without
      affecting the feature waveforms. As a pre-processing procedure, the adaptive
      morphological filter cleans an ECG signal to prepare it for further analysis. The
      noiseless ECG signal is embedded within a two-dimensional phase space to form a
      binary image and the identification of the feature waveforms is carried out based
      on the information presented by the image. The classification of the feature
      waveforms is implemented by an adaptive clustering technique according to the
      geometric information represented by the image in the phase space. Simulation
      studies on ECG records from the MIT-BIH and BIDMC databases have demonstrated the
      effectiveness and accuracy of the proposed methods. 

PMID- 24094826
TI  - Endothelial nitric oxide synthase and heme oxygenase-1 act independently in liver
      ischemic preconditioning.
AB  - BACKGROUND: ischemic preconditioning (IPC) protects against liver ischemia
      reperfusion (IR) injury. The mechanism involves nitric oxide metabolism but the
      importance of endothelial nitric oxide synthase (eNOS) has not been established.
      Heme oxygenase-1 (HO-1) protects against liver IR but it is unclear if this
      depends on nitric oxide synthase. MATERIALS AND METHODS: A mouse model of IPC
      with liver IR using wild-type (WT) and eNOS transgenic knockout (eNOS-/-) mice
      was developed to study the role of eNOS and its relationship to HO-1. Serum
      alanine aminotransferase level, liver histopathologic injury scores, and liver
      microcirculatory blood flow were measured. Western blots measured liver HO-1/2,
      eNOS, phosphorylated eNOS, inducible nitric oxide synthase, and reverse
      transcription-polymerase chain reaction (HO-1). A set of 24-h recovery
      experiments was undertaken on WT mice with measurement of serum alanine
      aminotransferase level, histologic injury score, and HO-1 by Western blot.
      RESULTS: In WT animals, IPC preceding IR resulted in a reduction in
      hepatocellular and histologic injury, and improvement in parenchymal perfusion.
      In contrast, IPC in the eNOS-/- model did not protect the animals from IR injury.
      There was no difference between the eNOS and phosphorylated eNOS expression in
      all the WT groups. HO-1 protein was not detected in the nonrecovery groups but HO
      1 messenger RNA was detected in all groups. In WT recovery experiments, IPC was
      protective against IR injury. HO-1 protein was detected in the IPC + IR and IR
      only groups but not in the sham group. CONCLUSIONS: This study developed and used
      an eNOS-/- model to demonstrate that eNOS mediates protection against liver IR
      injury by IPC. The eNOS expression and activity and HO-1 expression are increased
      independently in liver IPC and IR, with HO-1 expression increased in the later
      stages of IPC and IR.

PMID- 24094828
TI  - Letter regarding "release of hand burn contracture: comparing the ALT perforator
      flap with the gracilis free flap with split skin graft": a practice pearl.

PMID- 24094827
TI  - Hyperglycemia following recovery from hypoglycemia worsens endothelial damage and
      thrombosis activation in type 1 diabetes and in healthy controls.
AB  - BACKGROUND AND AIMS: Hypoglycemia produces thrombosis activation, but little
      attention has been paid to the effects of hyperglycemia following recovery from
      hypoglycemia on thrombosis activation. METHODS AND RESULTS: In both twenty-two
      healthy subjects and twenty-one matched persons with type 1 diabetes, recovery
      from a 2-h induced hypoglycemia was obtained by reaching normo-glycemia or
      hyperglycemia for another 2 h. After this, normal glycemia was maintained for the
      following 6 h. Hyperglycemia after hypoglycemia was also repeated with the
      concomitant infusion of vitamin C. In both controls and people with diabetes, the
      recovery with normo-glycemia was accompanied by a significant improvement of Von
      Willebrand factor (vWF), prothrombin fragment 1 + 2 (F1 + 2), thrombin
      antithrombin III-complexes (TAT), P-selectin, plasminogen activator inhibitor-1
      (PAI-1), nitrotyrosine and 8-iso-prostaglandin F2alpha (8-iso-PGF2alpha) (p <
      0.01 vs hypoglycemia for all the parameters), all directly affected by
      hypoglycemia itself (p < 0.01 vs baseline for all the parameters). On the
      contrary, the recovery with hyperglycemia after hypoglycemia worsens all these
      parameters (p < 0.01 vs normoglycemia for all the parameters), an effect
      persisting even after the additional 6 h of normo-glycemia. The effect of
      hyperglycemia following hypoglycemia was partially counterbalanced when vitamin C
      was infused (p < 0.01 vs hyperglycemia alone for all the parameters), suggesting
      that hyperglycemia following hypoglycemia may activate thrombosis through the
      oxidative stress production. CONCLUSION: This study shows that, in type 1
      diabetes as well as in controls, the way in which recovery from hypoglycemia
      takes place could play an important role in favoring the activation of thrombosis
      and oxidative stress, widely recognized cardiovascular risk factors.

PMID- 24094829
TI  - Type A interrupted aortic arch accompanied by intracranial aneurysms causing
      subarachnoid hemorrhage in an adult man.
AB  - Interrupted aortic arch anomaly (IAA) characterized by complete luminal
      dissociation between the ascending and descending aorta and accounting for less
      than 1% of all cases of congenital heart disease. IAA is a rare condition in
      infants that occurs approximately three times per million births. It is usually
      diagnosed and repaired during the neonatal period and is extremely rare in
      adults. We present the case of an adult man who was diagnosed with IAA
      accompanied by intracranial aneurysms causing subarachnoid hemorrhage and
      demonstrate the imaging findings with 256-slice computed tomography angiography
      and digital subtraction angiography. 

PMID- 24094830
TI  - Lung ultrasound for the evaluation of pulmonary congestion in outpatients: a
      comparison with clinical assessment, natriuretic peptides, and echocardiography.
AB  - OBJECTIVES: The aim of this study was to define the performance of lung
      ultrasound (LUS) compared with clinical assessment, natriuretic peptides, and
      echocardiography, to evaluate decompensation in patients with systolic heart
      failure (HF) in an outpatient clinic. BACKGROUND: Evaluation of pulmonary
      congestion in chronic HF is challenging. LUS has been recently proposed as a
      reliable tool for the semiquantification of extravascular lung water through
      assessment of B-lines. METHODS: This was a cohort study of patients with moderate
      to severe systolic HF. Receiver-operating characteristic (ROC) analyses were
      performed to compare LUS with a previously validated clinical congestion score
      (CCS), amino-terminal portion of B-type natriuretic peptide (NT-proBNP), E/e'
      ratio, chest x-ray, and 6-min walk test. RESULTS: Ninety-seven patients were
      enrolled. Decompensation was present in 57.7% of patients when estimated by CCS,
      68% by LUS, 53.6% by NT-proBNP, and 65.3% by E/e' >=15. The number of B-lines was
      correlated to NT-proBNP (r = 0.72; p < 0.0001), E/e' (r = 0.68; p < 0.0001), and
      CCS (r = 0.43; p < 0.0001). In ROC analyses, considering as reference for
      decompensation a combined method (E/e' >= 15 and/or NT-proBNP >1,000 pg/ml), LUS
      yielded a C-statistic of 0.89 (95% confidence interval: 0.82 to 0.96), providing
      the best accuracy with a cutoff >= 15 B-lines (sensitivity 85%, specificity 83%).
      A systematic approach using CCS, E/e', NT-proBNP, chest x-ray, and 6-min walk
      test in different combinations as reference for decompensation also corroborated
      this cutoff and found a similar accuracy for LUS. CONCLUSIONS: In an HF
      outpatient clinic, B-lines were significantly correlated with more established
      parameters of decompensation. A B-line >=15 cutoff could be considered for a
      quick and reliable assessment of decompensation in outpatients with HF.

PMID- 24094831
TI  - Role of echocardiography in patients with intravascular hemolysis due to
      suspected continuous-flow LVAD thrombosis.
AB  - OBJECTIVES: This study sought to characterize the echocardiographic findings of
      patients presenting with intravascular hemolysis (IVH) due to suspected
      continuous-flow left ventricular assist device (LVAD) pump thrombosis.
      BACKGROUND: LVAD patients who develop pump thrombosis often present with IVH.
      Echocardiography may be able to detect device dysfunction in this setting.
      METHODS: Continuous-flow LVAD patients presenting with IVH due to suspected pump
      thrombosis were identified. Patients underwent echocardiography with cannula
      Doppler flow velocity interrogation. Findings were compared with baseline and
      follow-up studies, and with 49 stable LVAD control patients. RESULTS: Of 145
      patients, 14 (10%) had IVH due to suspected pump thrombosis. The mean age was 55
      +/- 15 years, 93% were men, and 50% received LVAD as destination therapy. Mean
      duration between implantation and IVH was 231 +/- 218 days. Eleven (79%) patients
      presented with hemoglobinuria, 9 (64%) with jaundice, and 5 (36%) with acute
      heart failure. Reduced cannula diastolic flow velocity and increased
      systolic/diastolic (S/D) flow velocity ratio were the only echocardiographic
      parameters significantly different from controls (outflow cannula 0.3 +/- 0.2 m/s
      vs. 0.8 +/- 0.3 m/s, p = 0.03, and 5.9 +/- 2.8 vs. 1.7 +/- 0.7, p < 0.01,
      respectively), and were worse for IVH patients with acute heart failure compared
      with those without (outflow cannula 0.2 +/- 0.1 m/s vs. 0.5 +/- 0.2 m/s, p =
      0.04, and 7.2 +/- 3.3 vs. 5.3 +/- 2.0, p = 0.02, respectively). Outflow cannula
      diastolic flow velocity and S/D flow velocity ratio changed significantly from
      baseline (p = 0.01 and p < 0.01, respectively) in IVH patients, whereas systolic
      flow velocity did not change (p = 0.59). Odds ratios for outflow cannula
      diastolic flow velocity and S/D flow velocity ratio for predicting IVH were 0.60
      (95% confidence interval [CI]: 0.51 to 0.73), p = 0.02, and 2.45 (95% CI: 2.37 to
      2.52) p < 0.01, respectively. Corresponding inflow cannula values were similarly
      significant. Pump thrombosis was confirmed in 7 (50%) patients after LVAD
      retrieval. CONCLUSIONS: Reduced cannula diastolic flow velocity and increased S/D
      flow velocity ratio identified continuous-flow LVAD dysfunction in patients with
      IVH due to suspected pump thrombosis better than other echocardiographic
      parameters.

PMID- 24094832
TI  - Prevalence of metallo-beta-lactamase NDM-1-producing multi-drug resistant
      bacteria at two Pakistani hospitals and implications for public health.
AB  - BACKGROUND: The rapid spread of metallo-beta-lactamase producing clinical
      pathogens is a matter of great concern and with the addition of NDM-1 it poses
      more threat for public health as NDM-1 positive isolates show resistance to most
      of the antibiotics. The current study was carried out to determine the prevalence
      of extended-spectrum beta-lactamases (ESBLs) and metallo-beta-lactamases (MBLs),
      particularly NDM-1 in clinical multi-drug resistant isolates from two tertiary
      care hospitals in Pakistan. METHODS: A total of 356 clinical isolates were
      included in the study where 301 isolates were collected from the Pakistan
      Institute of Medical Sciences (PIMS), Islamabad and 55 were collected from the
      Mayo Hospital Lahore. The isolates were screened for ESBLs and MBLs production by
      phenotypic method and PCR was performed to detect the presence of blaVIM, blaIMP
      and blaNDM-1 genes. RESULTS: Out of 356 clinical isolates, 160 showed carbapenem
      resistance. Of these 160 isolates, 131 displayed MBLs production as accessed by
      combined disk method. In MBLs producing organisms, PCR amplification confirmed 31
      (23.6%) isolates harboring blaNDM-1 gene, 33 (25.1%) isolates having blaVIM gene
      and 2 (1.5%) isolates displaying blaIMP gene. Plasmid profile analysis of NDM-1
      positive organisms showed variable number of plasmids which were stable during
      serial passages in antibiotic free media. The prevalence of ESBL producing
      organisms was recorded to be 87.5%. CONCLUSION: The results show a high level of
      NDM-1 positive organisms from variety of samples at both hospitals, implicating
      the spread of MBL genes in clinical isolates.

PMID- 24094833
TI  - Adjusting for multiple clinical observers in an unbalanced study design using
      latent class models of true within-herd lameness prevalence in Danish dairy
      herds.
AB  - The elimination of misclassification bias introduced by multiple observers was
      evaluated and discussed based on an illustrative example using lameness
      prevalence in 80 Danish dairy herds. Data from 5073 cows from loose-housed
      cubicle herds larger than 100 cows were included in the analysis. Four trained
      observers performed clinical scoring on cow level and undertook a calibration
      test with 39 video sequences. The calibration test served both the purpose of
      estimating inter-observer agreement (PABAK=0.69) in accordance with previous
      results and to estimate the sensitivity (Se) and specificity (Sp) for each
      observer. In the absence of a gold standard for the clinical observations, a
      latent class analysis (LCA) evaluating the true within-herd lameness prevalence
      was used. Sensitivity amongst observers was fairly low (0.24-0.81) inducing a
      general underestimation of the true prevalence. Comparative analyses were made to
      assess the effect of grazing on the lameness prevalence in order to demonstrate
      the consequences of using unadjusted apparent prevalences (AP) compared to the
      true prevalences (TP). Lameness prevalence was higher in grazing herds using AP
      estimates (19.0% zero-grazing, 20.2% grazing); while the TP estimates showed the
      expected higher lameness prevalence in zero-grazing herds (42.3% vs. 35.9%).
      Hence, this study emphasizes the importance of adjusting for observer Se and Sp
      to obtain true prevalence and avoid false interpretation. 

PMID- 24094834
TI  - Myocardial infection due to Fusobacterium nucleatum.
AB  - Fusobacterium nucleatum is an anaerobic gram-negative bacillus, which inhabits
      the oropharynx, gastrointestinal tract, and female genital tract. Infections
      classically affect the head and neck. We report a patient with a myocardial mass
      due to F. nucleatum, initially thought to be a neoplasm, and discuss anaerobic
      cardiac infections. 

PMID- 24094835
TI  - Isolation of bacterial cerebrospinal fluid culture contaminants at a major
      military medical center.
AB  - In recent decades, bacterial meningitis rates have decreased secondary to the
      success of routine vaccinations. Ironically, the decreased incidence may
      contribute to the challenge of establishing accurate and timely diagnoses.
      Studies have suggested that in immunocompetent patients with normal cerebrospinal
      fluid (CSF) white blood cell counts (WBC), positive CSF cultures may be
      disregarded as presumed contaminants, making the initial CSF WBC increasingly
      relevant. This single-institution retrospective study sought to integrate
      clinical data with positive cultures in an era when CSF contaminants may be more
      commonly isolated in culture than true pathogens. A total of 7715 adult and
      pediatric CSF samples from 1995 to 2009 were obtained at a major military medical
      center. Clinical and laboratory data from 121 positive bacterial cultures were
      reviewed. Our bacterial CSF contamination rate (false positives) was 0.91%
      (70/7715). True-positive (TP) CSF cultures totaled 51 (0.66%). Among TPs, 16%
      (8/51) demonstrated normal CSF cell counts. The notably low 15-year CSF
      contamination rate of 0.91%, suggests that positive cultures are likely to
      represent true infection in our institution. We believe efforts to decrease the
      contamination rate are among the most cost-effective, while targeted clinical re
      evaluation for all patients with positive CSF cultures remains vital. In light of
      this data, a targeted approach to re-evaluating positive cultures while
      incorporating the clinical context remains prudent. 

PMID- 24094836
TI  - Evaluation of iNtRON VRE vanA/vanB real-time PCR for follow-up surveillance of
      VRE-infected or colonized patients.
AB  - The iNtRON vancomycin-resistant enterococci (VRE) vanA/vanB real-time PCR assay
      was directly applied to stool surveillance (direct-PCR). direct-PCR was compared
      to 2 culture-based methods using Enterococcosel broth (enrichment-culture) and
      ChromID VRE media. The positive broth of the enrichment-culture was submitted to
      phenotypic confirmation of subcultured colonies and genotyping by Seeplex VRE
      PCR. From September 2011 to May 2012, 208 stool specimens from 188 patients
      previously positive for VRE were enrolled. Enrichment-culture and direct-PCR
      detected 178 and 158 positives, respectively. Among 129 specimens cultured with
      ChromID, direct-PCR and ChromID yielded 105 and 104 positives, respectively.
      Compared to the enrichment-culture, sensitivity, specificity, positive predictive
      value (PPV), and negative predictive value (NPV) of direct-PCR and ChromID were
      86.0%, 83.3%, 96.8%, 50.0%, and 89.5%, 86.7%, 98.1%, 52.0%, respectively.
      Considering the excellent PPV and low NPV, direct-PCR would be useful to monitor
      VRE-colonized or infected patients on the day, but enrichment-culture is required
      for direct-PCR-negative specimens. 

PMID- 24094837
TI  - Nationwide survey of Helicobacter pylori antibiotic resistance in Thailand.
AB  - The objectives of this study are to survey the antibiotic-resistant pattern of
      Helicobacter pylori infection in different geographical locations in Thailand and
      to determine factors associated with antibiotic resistance. Dyspeptic patients
      undergoing upper gastrointestinal endoscopy from the Northern, Northeastern,
      Central, and Southern regions of Thailand between January 2004 and December 2012
      were enrolled in this study. Two antral gastric biopsies were obtained for
      culture; susceptibility tests were performed using E-test. A total of 3964 were
      enrolled, and 1350 patients (34.1%) were infected with H. pylori as identified by
      rapid urease test. Cultures were positive in 619 isolates. E-test for
      amoxicillin, clarithromycin, metronidazole, and tetracycline were successful in
      400 isolates and for levofloxacin and ciprofloxacin in 208 isolates. Antibiotic
      resistance was present in 50.3% including amoxicillin 5.2%, tetracycline 1.7%,
      clarithromycin 3.7%, metronidazole 36%, ciprofloxacin 7.7%, levofloxacin 7.2%,
      and multi-drugs in 4.2%. Clarithromycin resistance was significantly more common
      in those older than 40 years (i.e., 100% versus 0%; P = 0.04). The prevalence of
      metronidazole resistant in Southern Thailand was significantly higher than in the
      Northeastern region (66.7% versus 33.3% P = 0.04). Metronidazole resistance
      remains the most common antibiotic resistant type of H. pylori in Thailand. The
      pattern of H. pylori antibiotic resistance over 9 years demonstrated a fall in
      clarithromycin resistance such that currently age >40 years is a predictor for
      clarithromycin resistance in Thailand. Quinolone resistance is a growing problem.

PMID- 24094838
TI  - An engineered monomeric Zoanthus sp. yellow fluorescent protein.
AB  - Protein engineering has created a palette of monomeric fluorescent proteins
      (FPs), but there remains an ~30 nm spectral gap between the most red-shifted
      useful Aequorea victoria green FP (GFP) variants and the most blue-shifted useful
      Discosoma sp. red FP (RFP) variants. To fill this gap, we have engineered a
      monomeric version of the yellow FP (YFP) from Zoanthus sp. coral. Our preferred
      variant, designated as mPapaya1, displays excellent fluorescent brightness, good
      photostability, and retains its monomeric character both in vitro and in living
      cells in the context of protein chimeras. We demonstrate that mPapaya1 can serve
      as a good Forster resonance energy transfer (FRET) acceptor when paired with an
      mTFP1 donor. mPapaya1 is a valuable addition to the palette of FP variants that
      are useful for multicolor imaging and FRET-based biosensing.

PMID- 24094839
TI  - Perceptions of a reproductive health self-assessment tool (RH-SAT) in an urban
      community health center.
AB  - OBJECTIVE: Physicians face barriers to incorporating recommended contraceptive
      and preconception health services, including reproductive life plans (RLPs), into
      primary care. With promising findings from early studies of RLPs, we examined the
      impact of a novel reproductive health self-assessment tool (RH-SAT) on
      reproductive health counseling. METHODS: We created the RH-SAT for an urban
      community health center population and trained providers on preconception and
      contraceptive guidelines. Semi-structured interviews were conducted to assess
      perceptions of the tool with 22 patients and with all 15 providers at the clinic.
      Transcripts were thematically analyzed using a grounded theoretical approach.
      RESULTS: Patients and providers reported the RH-SAT presented new and thought
      provoking material that promoted patient participation and facilitated
      counseling. CONCLUSION: This RH-SAT is acceptable and useful to patients and
      providers in an underserved urban health center. In accordance with Medical
      Communication Alignment Theory (MCAT), increased patient participation in
      reproductive health discussions may alert providers to patient interest in these
      topics. PRACTICE IMPLICATIONS: This study provides preliminary evidence that the
      RH-SAT can help overcome barriers to reproductive health counseling in primary
      care. Providers may wish to incorporate tools into their practice to improve
      communication with patients about their reproductive health goals.

PMID- 24094840
TI  - A global research network for non-communicable diseases.

PMID- 24094841
TI  - The importance of the experiences of initial diagnosis and treatment failure when
      switching antiepileptic drugs.
AB  - We sought to understand the issues that lead from the need to change
      antiepileptic drugs (AEDs) and how this may influence someone's feelings
      regarding swapping to another drug. We conducted semistructured interviews with
      14 people with epilepsy, four months after changing from AED monotherapy.
      Interviews were digitally recorded, transcripts were coded independently, and
      thematic analysis was undertaken through group work. There were seven major
      themes: failure, the reason behind the failure, and the experience itself;
      expectations; previous experience; personality and life events; side effects;
      impact of diagnosis; and outcome. Clinical outcome and patients' ideas of outcome
      were often discordant. Each drug change arises from a position of failure that
      elicits strong feelings of loss of control and vulnerability in participants.
      Recognizing the need for counseling of targeted individuals undergoing AED change
      is key. Unresolved emotional issues surrounding biographical disruption following
      diagnosis were potent modifiers of the change process. 

PMID- 24094842
TI  - Microperfusion of 3-MPA into the brain augments GABA.
AB  - In vivo effects of microperfusion of a GABA synthesis inhibitor (3-MPA) into the
      striatum and hippocampus on amino acid concentrations and electrical neuronal
      activity were investigated. Paradoxical elevations in GABA in the striatum (5
      fold in anesthetized and 50-fold in awake rats) and hippocampus (2-fold in
      anesthetized and 15-fold in awake rats) were documented under steady-state
      concentrations of 3-MPA along with expected increases in glutamate (a 15-fold
      increase and a 250-fold increase in the striatum of anesthetized and awake rats,
      respectively; a 7-fold increase and a 25-fold increase in the hippocampus of
      anesthetized and awake rats, respectively). There was no clear epileptiform or
      seizure activity. Explanations for the paradoxical increase in GABA are offered,
      and emphasis is placed on the dependency of disinhibition on the model in which
      its effects are studied as well as on the prevailing level of activation of the
      probed network. 

PMID- 24094843
TI  - Cultural beliefs among people with epilepsy or physical impairment in Guinea
      Bissau: Differences and similarities.
AB  - People living with a disability in sub-Saharan Africa have poorer health
      outcomes, lower educational successes, less economic participation, and higher
      levels of poverty than people without disability. Disability-inclusive
      development promotes the involvement of people with disabilities in programs that
      reduce these inequalities. This requires a good understanding of how individuals
      with disability perceive their condition. In this study, we identified cultural
      beliefs among 31 individuals with epilepsy or physical impairment, known to a
      community-based rehabilitation service in Guinea-Bissau, using face-to-face
      interviews. We related these beliefs to religious background and type of
      disability. We found poor knowledge of and attitudes towards disability among
      persons with epilepsy and physical impairment. Cultural beliefs were
      significantly shaped by religious background. Islamic respondents were more
      positive about their disability as compared to Christians and traditional
      believers. A better understanding of cultural beliefs among people with
      disabilities may help to launch and adapt disability-inclusive community-based
      rehabilitation services. 

PMID- 24094844
TI  - Epilepsy-induced behavioral changes during the ictal phase.
AB  - In epilepsy, experiential phenomena and behavioral manifestations may pose a
      number of problems in terms of differential diagnosis. From a clinical point of
      view, ictal psychiatric symptoms represent partial seizures, mainly partial ones.
      In the majority of cases, they are very brief (lasting from a few seconds to a
      few minutes), stereotyped, out of context, and frequently associated with subtle
      or overt automatisms and postictal confusion of variable duration. In some cases,
      such symptoms are followed by alteration of consciousness as the ictus evolves to
      a complex partial seizure or a generalized tonic-clonic seizure. This paper
      reviews clinically relevant behavioral patterns during seizures discussing
      clinical phenomenology and relevance in terms of lateralizing value.

PMID- 24094845
TI  - Polytherapy with stiripentol: consider more than just metabolic interactions.

PMID- 24094846
TI  - A refined examination of the facial cues contributing to vicarious effects on
      self-pain and spinal responses.
AB  - Vicarious pain has been shown to enhance observers' nociceptive reactivity and
      pain perception. We exposed healthy participants to specific parts of facial pain
      expressions in order to investigate which components are required to induce this
      modulation. We created 2 classes of stimuli: one containing the most useful
      information for identification of pain expressions (diagnostic) and one
      containing the least useful information (antidiagnostic). Twenty-eight normal
      volunteers received electrical stimulation of the sural nerve immediately after
      they viewed these stimuli. Subjective ratings (intensity and unpleasantness) as
      well as the nociceptive flexion reflex (NFR) evoked by the shock were recorded.
      Results show that diagnostic stimuli lead to higher subjective ratings of shock
      pain than the antidiagnostic stimuli, but the stimuli classes had no significant
      impact on the NFR. A control experiment showed that our facial stimuli were given
      very low valence and arousal ratings compared to stimuli previously used to
      demonstrate the effect of emotional pictures on pain. Thus, the results are
      unlikely to be explained by emotions felt by the observer and suggest a vicarious
      facilitation of supraspinal pain processing induced by key features underlying
      pain expressions recognition. Results provide further support to the perception
      action model of empathy. PERSPECTIVE: This study demonstrates that visual
      features that are efficiently used for the recognition of pain expressions are
      sufficient to induce a vicarious facilitation of self-pain. Supraspinal pain
      responses were modulated by the informativeness of the areas of the pain
      expressions that participants viewed prior to the painful stimulations.

PMID- 24094847
TI  - A risk-adapted study of cisplatin and etoposide, with or without ifosfamide, in
      patients with metastatic seminoma: results of the GETUG S99 multicenter
      prospective study.
AB  - BACKGROUND: Whether patients with good prognosis and intermediate/poor prognosis
      advanced seminoma should be treated differently has not been defined. OBJECTIVE:
      To assess a risk-adapted chemotherapy regimen in patients with advanced seminoma.
      DESIGN, SETTING, AND PARTICIPANTS: A total of 132 patients were included in this
      prospective study. Patients with a good prognosis according to the International
      Germ Cell Cancer Collaboration Group (IGGCCG) were treated with four cycles of
      cisplatin-etoposide (EP). Patients with an intermediate prognosis according to
      the IGCCCG (or a poor prognosis according to the Medical Research Council
      classification) were treated with four cycles of VIP (EP and ifosfamide) and
      granulocyte colony-stimulating factor (G-CSF). OUTCOME MEASUREMENTS AND
      STATISTICAL ANALYSIS: Survival curves were estimated using the Kaplan-Meier
      method. RESULTS AND LIMITATIONS: The median follow-up was 4.5 yr (range: 0.4-11.6
      yr). Among 108 patients (82%) with a good prognosis who received EP, grade 3-4
      toxicity included neutropenia (47%) and neutropenic fever (12%). Among the 24
      patients (18%) with an intermediate/poor prognosis who received VIP plus G-CSF,
      toxicity included grade 3-4 neutropenia (36%), neutropenic fever (23%),
      thrombocytopenia (23%), anemia (23%), and a toxicity-related death (n=1; 4%). The
      3-yr progression-free survival (PFS) rate was 93% (range: 85-97%) in the good
      prognosis group and 83% (range: 63-93%) in the intermediate/poor prognosis group
      (p=0.03 for PFS). The 3-yr overall survival (OS) rate was 99% (range: 92-100%)
      and 87% (range: 67-95%), respectively (p<0.005 for OS). Only four patients died
      of seminoma or its treatment. CONCLUSIONS: A risk-adapted chemotherapy policy for
      advanced seminoma yielded an excellent outcome with a 3-yr OS rate of 96%.

PMID- 24094848
TI  - Acidity characterization of heterogeneous catalysts by solid-state NMR
      spectroscopy using probe molecules.
AB  - Characterization of the surface acidic properties of solid acid catalysts is a
      key issue in heterogeneous catalysis. Important acid features of solid acids,
      such as their type (Bronsted vs. Lewis acid), distribution and accessibility
      (internal vs. external sites), concentration (amount), and strength of acid sites
      are crucial factors dictating their reactivity and selectivity. This short review
      provides information on different solid-state NMR techniques used for acidity
      characterization of solid acid catalysts. In particular, different approaches
      using probe molecules containing a specific nucleus of interest, such as pyridine
      d5, 2-(13)C-acetone, trimethylphosphine, and trimethylphosphine oxide, are
      compared. Incorporation of valuable information (such as the adsorption
      structure, deprotonation energy, and NMR parameters) from density functional
      theory (DFT) calculations can yield explicit correlations between the chemical
      shift of adsorbed probe molecules and the intrinsic acid strength of solid acids.
      Methods that combine experimental NMR data with DFT calculations can therefore
      provide both qualitative and quantitative information on acid sites. 

PMID- 24094849
TI  - Temporal lobe surgery in medically refractory epilepsy: a comparison between
      populations based on MRI findings.
AB  - INTRODUCTION: High resolution MRI findings suggestive of mesial temporal
      sclerosis (MRI-MTS) correlate with good outcome after surgery. However, a large
      group of patients present with normal brain MRI (N-MRI) and temporal lobe
      epilepsy (TLE). We aim to compare pre-operative ictal EEG patterns in predicting
      surgical outcomes in the population with MRI-MTS vs. N-MRI after selective
      anterior-mesial temporal lobe (AMTL) resection. METHODS: 241 patients with
      unilateral anterior ictal EEG findings underwent selective AMTL resection. 143
      MRI-MTS and 98 N-MRI patients were identified. Outcome was based on the modified
      Engel classification, ictal EEG pattern at seizure onset, demographics and MRI
      findings. RESULTS: Seizure-free outcome was seen in the MRI-MTS in 79% of
      patients, compared to 59.1% (p<.005) of the N-MRI group. No significant
      difference was identified in ictal EEG patterns at presentation between groups.
      Class I outcome was achieved in 78.9% of patients that had theta rhythm and MRI
      MTS compared to 57.9% of patients that had theta rhythm and N-MRI (p<0.05).
      DISCUSSION AND CONCLUSION: Surgical treatment for mesial TLE is effective.
      Positive MRI suggestive of mesial temporal sclerosis (MTS) predicts better
      seizure control after surgery. Theta rhythm is the most common ictal pattern and
      seems to carry the best prognosis for TLE. However, a well-selected group of
      patients with N-MRI will benefit from surgical intervention, and similar outcome
      to MRI-MTS patients can be achieved if delta ictal EEG pattern is presented at
      initial onset. Early referral to an epilepsy center cannot be emphasized enough,
      even in situations when high-resolution brain MRI is normal.

PMID- 24094850
TI  - Negative emotional outcomes attenuate sense of agency over voluntary actions.
AB  - Sense of agency (SoA) refers to the feeling that one's voluntary actions produce
      external sensory events [1, 2]. Several psychological theories hypothesized links
      between SoA and affective evaluation [3-6]. For example, people tend to attribute
      positive outcomes to their own actions, perhaps reflecting high-level narrative
      processes that enhance self-esteem [3]. Here we provide the first evidence that
      such emotional modulations also involve changes in the low-level sensorimotor
      basis of agency. The intentional binding paradigm [1] was used to quantify the
      subjective temporal compression between a voluntary action and its sensory
      consequences, providing an implicit measure of SoA. Emotional valence of action
      outcomes was manipulated by following participants' key-press actions with
      negative or positive emotional vocalizations [7], or neutral sounds. We found
      that intentional binding was reduced for negative compared to positive or neutral
      outcomes. Discriminant analyses identified a change in time perception of both
      actions and their negative outcomes, demonstrating that the experience of action
      itself is subject to affective modulation. A small binding benefit was also found
      for positive action outcomes. Emotional modulation of SoA may contribute to
      regulating social behavior. Correctly tracking the valenced effects of one's
      voluntary actions on other people could underlie successful social interactions. 

PMID- 24094851
TI  - miRNAs are required for generating a time delay critical for the circadian
      oscillator.
AB  - BACKGROUND: Circadian clocks coordinate an organism's activities and regulate
      metabolic homeostasis in relation to daily environmental changes, most notably
      light/dark cycles. As in other organisms, the timekeeping mechanism in mammals
      depends on a self-sustaining transcriptional negative feedback loop with a built
      in time delay in feedback inhibition. Although the time delay is essential for
      generating a slow, self-sustaining negative feedback loop with a period close to
      24 hr, the exact mechanisms underlying the time delay are not known. RESULTS:
      Here, we show that RNAi mediated by microRNAs (miRNAs) is an essential mechanism
      in generating the time delay. In Dicer-deficient (and thus miRNA-deficient) cells
      and mice, circadian rhythms were dramatically shortened (by ~2 hr), although the
      rhythms remained robust. The period shortening was caused by faster PER1 and PER2
      translation in the Dicer-deficient cells. We also identified three specific
      miRNAs that regulate Per expression and showed that knockdown of these miRNAs in
      wild-type cells also shortened the circadian period. CONCLUSIONS: Consistent with
      the canonical function of miRNAs as translational modulators of target genes and
      their widespread roles in cell physiology, circadian rhythms are also modulated
      by miRNA-mediated RNAi acting on posttranscriptional regulation of key clock
      genes. Our present study definitively shows that RNAi is an important modulator
      of circadian rhythms by controlling the pace of PER synthesis and presents a
      novel layer of regulation for the clock.

PMID- 24094852
TI  - Decoding the brain's algorithm for categorization from its neural implementation.
AB  - Acts of cognition can be described at different levels of analysis: what behavior
      should characterize the act, what algorithms and representations underlie the
      behavior, and how the algorithms are physically realized in neural activity [1].
      Theories that bridge levels of analysis offer more complete explanations by
      leveraging the constraints present at each level [2-4]. Despite the great
      potential for theoretical advances, few studies of cognition bridge levels of
      analysis. For example, formal cognitive models of category decisions accurately
      predict human decision making [5, 6], but whether model algorithms and
      representations supporting category decisions are consistent with underlying
      neural implementation remains unknown. This uncertainty is largely due to the
      hurdle of forging links between theory and brain [7-9]. Here, we tackle this
      critical problem by using brain response to characterize the nature of mental
      computations that support category decisions to evaluate two dominant, and
      opposing, models of categorization. We found that brain states during category
      decisions were significantly more consistent with latent model representations
      from exemplar [5] rather than prototype theory [10, 11]. Representations of
      individual experiences, not the abstraction of experiences, are critical for
      category decision making. Holding models accountable for behavior and neural
      implementation provides a means for advancing more complete descriptions of the
      algorithms of cognition. 

PMID- 24094853
TI  - Striated rootlet and nonfilamentous forms of rootletin maintain ciliary function.
AB  - Primary cilia are microtubule-based sensory organelles whose structures and
      functions must be actively maintained throughout animal lifespan to support
      signal transduction pathways essential for development and physiological
      processes such as vision and olfaction [1]. Remarkably, few cellular components
      aside from the intraflagellar transport (IFT) machinery are implicated in ciliary
      maintenance [2]. Rootletin, an evolutionarily conserved protein found as
      prominent striated rootlets or a nonfilamentous form, both of which are
      associated with cilium-anchoring basal bodies, represents a likely candidate
      given its well-known role in preventing ciliary photoreceptor degeneration in a
      mouse model [3, 4]. Whether rootletin is universally required for maintaining
      ciliary integrity, and if so, by what mechanism, remains unresolved. Here, we
      demonstrate that the gene disrupted in the previously isolated C. elegans
      chemosensory mutant che-10 encodes a rootletin ortholog that localizes proximally
      and distally to basal bodies of cilia harboring or lacking conspicuous rootlets.
      In vivo analyses reveal that CHE-10/rootletin maintains ciliary integrity partly
      by modulating the assembly, motility, and flux of IFT particles, which are
      critical for axoneme length control. Surprisingly, CHE-10/rootletin is also
      essential for stabilizing ciliary transition zones and basal bodies, roles not
      ascribed to IFT. Unifying these findings, we provide evidence that the underlying
      molecular defects in the che-10 mutant stem from disrupted organization/function
      of the periciliary membrane, affecting the efficient delivery of basal body
      associated and ciliary components and resulting in cilium degeneration. Together,
      our cloning and functional analyses of C. elegans che-10 provide the first
      mechanistic insights into how filamentous and nonfilamentous forms of rootletin
      play essential roles in maintaining ciliary function in metazoans. 

PMID- 24094854
TI  - Budding yeast escape commitment to the phosphate starvation program using gene
      expression noise.
AB  - Cells must rapidly adapt to changes in nutrient availability. In budding yeast,
      limitation of phosphate rapidly induces the expression of the Pho regulon genes
      [1-4]. This starvation program depends on the transcription factor Pho4, which
      translocates to the nucleus within minutes when cells are transferred to a low
      phosphate medium [5]. Contrasting its rapid induction, we report that the Pho
      regulon can remain induced for dozens of generations in cells transferred back to
      high phosphate levels. For example, about 40% of the cells that were starved for
      2 hr maintained PHO4-dependent expression for over eleven generations of growing
      in high phosphate. This commitment to activation of the Pho regulon depends on
      two feedback loops that reduce internal phosphate, one through induction of the
      PHM1-4 genes that increase phosphate storage in the vacuoles and the second by
      induction of SPL2, which reduces incoming flux by inhibiting low-affinity
      transporters. Noise in SPL2 expression allows stochastic repression of the Pho
      regulon in committed cells growing at high phosphate, as we demonstrate using a
      novel method, DAmP multiple copy array (DaMCA), that reduces intrinsic noise in
      gene expression while maintaining mean abundance. Commitment is an integral part
      of the dual-transporter motif that helps cells prepare for nutrient depletion. 

PMID- 24094855
TI  - Halotropism is a response of plant roots to avoid a saline environment.
AB  - Tropisms represent fascinating examples of how plants respond to environmental
      signals by adapting their growth and development. Here, a novel tropism is
      reported, halotropism, allowing plant seedlings to reduce their exposure to
      salinity by circumventing a saline environment. In response to a salt gradient,
      Arabidopsis, tomato, and sorghum roots were found to actively prioritize growth
      away from salinity above following the gravity axis. Directionality of this
      response is established by an active redistribution of the plant hormone auxin in
      the root tip, which is mediated by the PIN-FORMED 2 (PIN2) auxin efflux carrier.
      We show that salt-induced phospholipase D activity stimulates clathrin-mediated
      endocytosis of PIN2 at the side of the root facing the higher salt concentration.
      The intracellular relocalization of PIN2 allows for auxin redistribution and for
      the directional bending of the root away from the higher salt concentration. Our
      results thus identify a cellular pathway essential for the integration of
      environmental cues with auxin-regulated root growth that likely plays a key role
      in plant adaptative responses to salt stress. 

PMID- 24094856
TI  - Phylogenomics resolves evolutionary relationships among ants, bees, and wasps.
AB  - Eusocial behavior has arisen in few animal groups, most notably in the aculeate
      Hymenoptera, a clade comprising ants, bees, and stinging wasps [1-4]. Phylogeny
      is crucial to understanding the evolution of the salient features of these
      insects, including eusociality [5]. Yet the phylogenetic relationships among the
      major lineages of aculeate Hymenoptera remain contentious [6-12]. We address this
      problem here by generating and analyzing genomic data for a representative series
      of taxa. We obtain a single well-resolved and strongly supported tree, robust to
      multiple methods of phylogenetic inference. Apoidea (spheciform wasps and bees)
      and ants are sister groups, a novel finding that contradicts earlier views that
      ants are closer to ectoparasitoid wasps. Vespid wasps (paper wasps, yellow
      jackets, and relatives) are sister to all other aculeates except chrysidoids.
      Thus, all eusocial species of Hymenoptera are contained within two major groups,
      characterized by transport of larval provisions and nest construction, likely
      prerequisites for the evolution of eusociality. These two lineages are
      interpolated among three other clades of wasps whose species are predominantly
      ectoparasitoids on concealed hosts, the inferred ancestral condition for
      aculeates [2]. This phylogeny provides a new framework for exploring the
      evolution of nesting, feeding, and social behavior within the stinging
      Hymenoptera. 

PMID- 24094857
TI  - Nuclear repulsion enables division autonomy in a single cytoplasm.
AB  - BACKGROUND: Current models of cell-cycle control, based on classic studies of
      fused cells, predict that nuclei in a shared cytoplasm respond to the same CDK
      activities to undergo synchronous cycling. However, synchrony is rarely observed
      in naturally occurring syncytia, such as the multinucleate fungus Ashbya
      gossypii. In this system, nuclei divide asynchronously, raising the question of
      how nuclear timing differences are maintained despite sharing a common milieu.
      RESULTS: We observe that neighboring nuclei are highly variable in division-cycle
      duration and that neighbors repel one another to space apart and demarcate their
      own cytoplasmic territories. The size of these territories increases as a nucleus
      approaches mitosis and can influence cycling rates. This nonrandom nuclear
      spacing is regulated by microtubules and is required for nuclear asynchrony, as
      nuclei that transiently come in very close proximity will partially synchronize.
      Sister nuclei born of the same mitosis are generally not persistent neighbors
      over their lifetimes yet remarkably retain similar division cycle times. This
      indicates that nuclei carry a memory of their birth state that influences their
      division timing and supports that nuclei subdivide a common cytosol into
      functionally distinct yet mobile compartments. CONCLUSIONS: These findings
      support that nuclei use cytoplasmic microtubules to establish "cells within
      cells." Individual compartments appear to push against one another to compete for
      cytoplasmic territory and insulate the division cycle. This provides a mechanism
      by which syncytial nuclei can spatially organize cell-cycle signaling and
      suggests size control can act in a system without physical boundaries.

PMID- 24094858
TI  - Presence of paraneoplastic antibodies in non-carcinomatous patients with
      neurological involvements of unknown cause.
AB  - BACKGROUND: Paraneoplastic antibodies (PAs) play a crucial role in the diagnostic
      approach of paraneoplastic neurological syndrome (PNS). We clarified the
      frequency and the clinical profile of PA-positive non-carcinomatous patients with
      neurological involvements of unknown cause. METHODS: PAs were analyzed in sera of
      222 consecutive non-carcinomatous patients (122 men and 100 women) defined as
      acute or subacute onset of unknown-causative symptoms involving the neuromuscular
      junction, the central and/or the peripheral nervous system between 2006 and 2009.
      PAs contained antineuronal nuclear autoantibody type 1, 2, 3, Purkinje cell
      cytoplasmic autoantibody type 1, 2, anti-Tr, amphiphysin, CRMP-5, P/Q-type, N
      type voltage-gated calcium channels (VGCC), voltage-gated potassium channel
      complex (VGKCC) and neuronal acetylcholine receptor (nAChR) antibodies. PA
      seropositive patients received detailed examination of carcinoma in the whole
      body for the following 2 years. RESULTS: Nine patients were PA-positive. VGKCC
      antibodies were found in four patients, P/Q-type VGCC antibodies in two, N-type
      VGCC antibodies in two and nAChR antibodies in one. Neurological features
      revealed limbic encephalitis in four patients, sensorimotor neuropathy in three
      and Lambert-Eaton myasthenic syndrome in two. One year later, 2 patients
      developed myelodysplastic syndrome and lung adenocarcinoma (one patient each).
      CONCLUSION: We conclude that PA-seropositive frequency is 4.1% in non
      carcinomatous neurological patients at examination. VGKCC, P/Q-type and N-type
      VGCC, and nAChR antibodies have benefits for screening non-carcinomatous PNS
      patients with acute or subacute neurological deficits of unknown cause.

PMID- 24094859
TI  - The neurological effects of methyl bromide intoxication.
AB  - Used primarily as a fumigant or as a substrate in chemical processes, methyl
      bromide is a highly toxic gas. The gas is usually absorbed by inhalation and
      effects on the lungs, gastrointestinal tract, skin, and brain are seen. Numerous
      instances of acute and chronic neurologic injury have been reported: acute
      poisoning results in seizures, myoclonus, ataxia or cerebral oedema beginning as
      early as 30 min after exposure while subacute or chronic intoxication presents
      with diverse slowly progressive neurological and neurobehavioral symptoms. Serum
      bromide levels may be elevated, but often return rapidly to normal.
      Electroencephalography may show frontally-predominant slow waves or polyspikes
      with following slow wave, and MRI reveals characteristic involvement in the
      dentate nucleus of the cerebellum, the brainstem, and the splenium of the corpus
      callosum. Symmetric and selective lesions in characteristic sites are observed on
      imaging and on histopathological examination. These are likely produced by
      methylation of intracellular lipids, protein and glutathione; production of toxic
      metabolites; defective neurotransmitter function; and abnormal oxidative
      phosphorylation. This article reviews the toxic effects of this gas, the
      pathophysiology and symptoms of its effects on the nervous system, and
      characteristic findings on MRI; and presents an illustrative case of methyl
      bromide intoxication due to exposure at a factory producing the compound
      commercially.

PMID- 24094860
TI  - Increasing and persistent DWI changes in a patient with hereditary diffuse
      leukoencephalopathy with spheroids.
AB  - We report a case with genetically confirmed hereditary diffuse
      leukoencephalopathy with spheroids with distinctive MRI features. A 52-year-old
      woman with a family history of juvenile dementia presented with an 18-month
      history of progressive cognitive decline. Longitudinal magnetic resonance imaging
      studies of the brain revealed increasing and persistent white matter
      hyperintensities on diffusion-weighted images. Linear high intensity signal along
      axonal fibers arisen from the cerebral cortex was also shown. Finding of
      subcortical calcifications was noted on brain CT scan. Sequence analysis of CSF1R
      showed a novel missense mutation c.2467C>T (p.Ala823Val). Persistent and
      increasing diffusion on magnetic resonance image, presumably reflecting
      intramyelinic oedema in regions of neurodegeneration, is a distinctive feature
      observed in this case. The presence of this unique finding can be a diagnostic
      clue in the early stage of the disease. 

PMID- 24094861
TI  - A tale of two specificities: bispecific antibodies for therapeutic and diagnostic
      applications.
AB  - Artificial manipulation of antibody genes has facilitated the production of
      several unique recombinant antibody formats, which have highly important
      therapeutic and biotechnological applications. Although bispecific antibodies
      (bsAbs) are not new, they are coming to the forefront as our knowledge of the
      potential efficacy of antibody-based therapeutics expands. The next generation of
      bsAbs is developing due to significant improvements in recombinant antibody
      technologies. This review focuses on recent advances with a particular focus on
      improvements in format and design that are contributing to the resurgence of
      bsAbs, and in particular, on innovative structures applicable to next generation
      point-of-care (POC) devices with applicability to low resource environments. 

PMID- 24094862
TI  - Dissecting the assays to assess microbial tolerance to toxic chemicals in
      bioprocessing.
AB  - Microbial strains are increasingly used for the industrial production of
      chemicals and biofuels, but the toxicity of components in the feedstock and
      product streams limits process outputs. Selected or engineered microbes that
      thrive in the presence of toxic chemicals can be assessed using tolerance assays.
      Such assays must reasonably represent the conditions the cells will experience
      during the intended process and measure the appropriate physiological trait for
      the desired application. We review currently used tolerance assays, and examine
      the many parameters that affect assay outcomes. We identify and suggest the use
      of the best-suited assays for each industrial bioreactor operating condition,
      discuss next-generation assays, and propose a standardized approach for using
      assays to examine tolerance to toxic chemicals. 

PMID- 24094863
TI  - Cardiac anaphylaxis: searching for clarity.

PMID- 24094864
TI  - Electrocardiographic changes after injury in a rat model of combined crush
      injury.
AB  - BACKGROUND: Crush injury from debris, combined with hypoxia and water and food
      deprivation (combined crush injury), is common in industrial accidents and events
      such as earthquakes and terrorist attacks. Whether electrocardiographic changes
      are associated with combined crush injury is unclear. METHODS: Thirty-six rats
      underwent electrocardiography at baseline then were randomly assigned to 6 groups
      of 6. Bilateral hind limbs of all rats were compressed with custom-made clips
      (pressure 4.5 +/- 0.3 kg), and the rats were put into a hypoxic compartment
      (oxygen concentration 10% +/- 0.1%) for 72 hours without food or water. After 72
      hours, the rats were moved to a normoxic environment, where the clips were
      removed (decompression) and food and water were freely accessible.
      Electrocardiography was performed in a different group at each of days 0, 1, 3,
      7, 14, and 28 after decompression. RESULTS: One rat died at 0.6 days. Among the
      remaining 35 rats, 28 (80%) had abnormal electrocardiographic changes: ST-segment
      depression (n = 25), tall-peaked T waves (n = 16), arrhythmias (n = 4), abnormal
      Q waves (n = 2), wide QRS complexes (n = 2) and QT prolongation (n = 1). The
      abnormality rates among assessed rats were 100% on days 0, 1, and 3; 83% on day
      7; and 50% on days 14 and 28. CONCLUSIONS: The findings suggest that abnormal
      electrocardiographic changes were seen in rats after simulated combined crush
      injury and decompression and were slow to resolve.

PMID- 24094865
TI  - Outcomes of patients admitted for hanging injuries with decreased consciousness
      but without cardiac arrest.
AB  - OBJECTIVE: The objective of this study is to provide appropriate treatment of
      patients who showed decreased mentality but did not suffer cardiac arrest (CA)
      from hanging injury, from reviewing the characteristics and analyzing the
      outcomes in such patients. METHODS: A retrospective review of victims with
      decreased mentality but without CA due to hanging presenting to 2 tertiary
      general hospitals between January 2005 and August 2011 was performed. Treatments
      and examinations were evaluated, and the outcomes were assessed by cerebral
      performance category at hospital discharge. RESULTS: A total of 21 patients were
      included, and their initial Glasgow Coma Scale scores were between 3 and 11. No
      one received therapeutic hypothermia, but all regained consciousness
      spontaneously and were discharged with cerebral performance category 1. They
      received only conservative treatment such as respiratory care, fever control, and
      inotropic use. Computed tomography and magnetic resonance imaging studies
      revealed no definite abnormality if the patient did not show abnormal symptom and
      sign. CONCLUSION: Unconscious patients without CA from hanging could recover
      consciousness through conservative treatment.

PMID- 24094866
TI  - Imaging in the NEXUS-negative patient: when we break the rule.
AB  - BACKGROUND: In spite of general acceptance and validation of NEXUS (National
      Emergency X-Radiography Utilization Study) in the clearance of cervical spine (C
      spine) immobilized patients, clinicians often elect to image NEXUS-negative
      patients in clinical practice. OBJECTIVES: We sought to determine which variables
      (patient age, mechanism of injury, provider level of training, provider self
      reported motivation) contribute to the decision of emergency medicine providers
      to image NEXUS-negative patients. METHODS: This is a prospective observational
      study of patients with blunt trauma and risk for C-spine injury who did not meet
      "trauma team activation" criteria. Providers at one high-volume emergency
      department (ED) prospectively recorded NEXUS criteria, as well as rationale for
      imaging NEXUS-negative patients. Researchers then retrospectively queried the
      electronic medical record for patient age, mechanism of injury, and results of
      diagnostic imaging. Study data were analyzed with chi(2) and descriptive
      statistics. RESULTS: Three hundred patients were enrolled; 169 patients received
      C-spine imaging, of whom 53 were NEXUS-negative. There was no difference in
      imaging of NEXUS-negative patients as a factor of medical provider level of
      training (P=0.42). Of NEXUS-negative patients receiving imaging, 51 (96%) were
      older than 65 years, and 52 were being evaluated for a fall on level ground.
      Imaging revealed 7 positive findings. Two of these injuries were in NEXUS
      negative patients. CONCLUSION: Regardless of level of training, providers in our
      ED often imaged patients who met NEXUS low-risk criteria. This was mot common in
      geriatric patients who presented after falls. This digression from NEXUS led to
      the diagnosis of significant injuries in 2 patients which would otherwise have
      been missed.

PMID- 24094867
TI  - [Is the court-ordered treatment indication by the expert based on a medical
      diagnosis?].
AB  - Court-ordered treatment was created in 1998, as part of a law against sexual
      offense recidivism. The creation of court-ordered treatment is based on the
      premise that many offenders have psychiatric disorders. If the court-ordered
      treatment is appraised as an effective way to prevent recidivism by the lawmaker,
      the preeminent role of psychiatry, in the prevention of recidivism has generated
      controversy in the psychiatric community. Few studies have been conducted on
      court-ordered treatment in France, and have concerned epidemiological measures.
      Court-ordered treatment leads to an extension of the expert's mission. In order
      to prevent recidivism, the interest of a treatment is a new part of the expert's
      mission. PURPOSE: The main purpose of this study was to assess the kind of
      diagnosis reported by the forensic psychiatrist who considered the court-ordered
      treatment as appropriate. METHOD: We led a descriptive and retrospective study
      among the experts' reports of 68 subjects followed by three psychiatrists. We
      categorized each diagnosis found in the experts' reports in reference to DSM-IV
      TR axis I and axis II. As the expert has no obligation to refer to the DSM-IV-TR,
      we also considered the "no DSM-IV-TR categorized disorder" as a category. The
      primary outcome was the proportion of each diagnosis category in experts'
      reports, in which the forensic psychiatrist agreed with the indication of a court
      ordered treatment. RESULTS: We analysed 123 experts' reports in which the mission
      was to diagnose a mental disorder and to assess the need for a court-ordered
      treatment. The expert agreed with the need for a court-ordered treatment in 112
      reports. In those reports the diagnosis was "no disorder" in 27% of them, "no DSM
      IV-TR categorized disorder" in 26% of them, "axis II disorder" in 24% of them,
      "axis I disorder" in 19% of them, and "association of an axis I and an axis II
      disorder" in 4% of them. DISCUSSION: The diagnoses were heterogeneous. Their
      associations with the need for a court-ordered treatment seem to be contradictory
      when considering the association between "no mental disorder" and "need for a
      court-ordered treatment" found in 27% of the reports. These paradoxical results
      led us to question the meaning of mental disorder and treatment.

PMID- 24094868
TI  - The prevalence of overweight and obesity in a breast clinic population:
      consideration for weight loss as a therapeutic intervention.
AB  - BACKGROUND: Obesity is an important risk factor for breast cancer and weight loss
      may be associated with a decreased risk for breast cancer and its recurrence. We
      evaluated the prevalence of overweight, obesity, and obesity-related co
      morbidities in a breast health clinic population to determine the potential need
      for weight loss intervention. METHODS: A retrospective review was conducted of
      sequential patients seen at a breast health clinic from July 1 to December 31,
      2011. Body mass index (BMI), reason for visit (breast cancer diagnosis, high risk
      for breast cancer, or benign condition), and presence of obesity-related co
      morbidities were recorded. RESULTS: The 302 patients who met inclusion criteria
      had a median age of 52 years (10-91) and median BMI of 26 kg/m(2) (15.4-56.5).
      Overall, 36.8% of patients had a BMI between 18.5-24.9 kg/m(2); 32.1%, 25-29.9
      kg/m(2); 14.2%, 30-34.9 kg/m(2); 8.3%, 35-39.9 kg/m(2); and 4.3%, >= 40 kg/m(2).
      Overweight or obesity (BMI >= 25 kg/m(2)) occurred in 64.2% of breast cancer,
      65.0% of high-risk, and 57.1% of benign patients (P value not significant).
      Criteria for bariatric surgery (BMI 35-39.9 kg/m(2) with >= 1 obesity-related co
      morbidity or BMI >= 40 kg/m(2)) were met in 8.2% of breast cancer, 16.7% of high
      risk, and 11.5% of benign patients (P value not significant). CONCLUSIONS:
      Regardless of diagnosis, a significant proportion of patients visiting the breast
      health clinic meet criteria for weight loss intervention, including bariatric
      surgery. Weight management represents an underutilized therapeutic modality that
      could potentially decrease the risk of breast cancer and its recurrence, and
      improve overall prognosis.

PMID- 24094869
TI  - Outpatient laparoscopic sleeve gastrectomy in a free-standing ambulatory surgery
      center: first 250 cases.
AB  - BACKGROUND: A growing body of evidence supports the laparoscopic sleeve
      gastrectomy (LSG) as a safe and effective procedure for sustained weight loss and
      amelioration of weight-related co-morbidities. Procedures performed in ambulatory
      surgery centers (ASC) can provide several advantages over hospital-based surgery.
      We present our results of 250 consecutive patients undergoing LSG in an ASC. The
      objective of this study was to assess the safety and efficacy of outpatient LSG
      in a freestanding ASC. METHODS: Data was collected prospectively from 250
      consecutive patients who underwent LSG at a freestanding ASC. Patients were
      excluded from the ASC if they weighed>450 pounds, if anticipated operative time
      was>2 hours, if the patient had impaired mobility limiting early ambulation, or
      if there were medical problems requiring postoperative monitoring beyond 23
      hours. Revisions were not included in this study. RESULTS: Mean age was 47 years
      (range, 23-74 yr). Mean preoperative body mass index (BMI) was 43 kg/m2 (29-71
      kg/m2). Mean operative time was 60 minutes (31-161 min). Mean recovery room time
      was 131 minutes (30-385 min). Mean percent excess weight loss (%EWL) was 60% at 1
      year and 63% at 2 years. Nine patients (3.6%) were readmitted within 30 days. Two
      patients (.8%) were transferred from the ASC to a hospital. There was 1 staple
      line leak (.4%). There were no open conversions and no deaths. CONCLUSIONS: LSG
      can be performed safely in a freestanding ASC in select patients with outcomes
      comparable to the inpatient standard. Additional studies are needed to formulate
      selection criteria and guidelines to maximize patient safety and outcomes.

PMID- 24094870
TI  - Twelve-year results for revisional gastric bypass after failed restrictive
      surgery in 131 patients.
AB  - BACKGROUND: Gastric banding (GB) and vertical banded gastroplasty (VBG) may
      result in unsatisfactory weight loss or intolerable side effects. Such outcomes
      are potential indications for additional bariatric surgery, and Roux-en-Y gastric
      bypass is frequently used at such revisions (rRYGB). The present study examined
      long-term results of rRYGB. METHODS: In total, 175 patients who had undergone
      rRYGB between 1993 and 2003 at 2 university hospitals received a questionnaire
      regarding their current status. The questionnaire was returned by 131 patients
      (75% follow-up rate, 66 VBG and 65 GB patients). Blood samples were obtained and
      medical charts studied. The reason for conversion was mainly unsatisfactory
      weight loss among the VBG patients and intolerable side effects among GB
      patients. RESULTS: The 131 patients (112 women), mean age 41.8 years at rRYGB,
      were evaluated at mean 11.9 years (range 7-17) after rRYGB. Mean body mass index
      of those with prior unsatisfactory weight loss was reduced from 40.1 kg/m(2)
      (range 28.7-52.2) to 32.6 kg/m(2) (range 19.1-50.2) (P<.01). Only 2 patients (2%)
      underwent additional bariatric surgery after rRYGB. The overall result was
      satisfactory for 74% of the patients. Only 21% of the patients adhered to the
      recommendation of lifelong multivitamin supplements while 76% took vitamin B12.
      Anemia was present in 18%. CONCLUSIONS: rRYGB results in sustained weight loss
      and satisfied patients when VBG or GB have failed. Subsequent bariatric surgery
      was rare but micronutrient deficiencies were frequent.

PMID- 24094871
TI  - Comment on: Improvement in gastroesophageal reflux disease symptoms after various
      bariatric procedures: review of the Bariatric Outcomes Longitudinal Database.

PMID- 24094872
TI  - Endoscopic findings with severely symptomatic esophagitis from an overly
      restrictive laparoscopic adjustable gastric band.

PMID- 24094873
TI  - Comment on: The prevalence of overweight and obesity in a breast clinic
      population: consideration for weight loss as a therapeutic intervention.

PMID- 24094874
TI  - Long-term dysregulation of brain corticotrophin and glucocorticoid receptors and
      stress reactivity by single early-life pain experience in male and female rats.
AB  - Inflammatory pain experienced on the day of birth (postnatal day 0: PD0)
      significantly dampens behavioral responses to stress- and anxiety-provoking
      stimuli in adult rats. However, to date, the mechanisms by which early life pain
      permanently alters adult stress responses remain unknown. The present studies
      examined the impact of inflammatory pain, experienced on the day of birth, on
      adult expression of receptors or proteins implicated in the activation and
      termination of the stress response, including corticotrophin releasing factor
      receptors (CRFR1 and CRFR2) and glucocorticoid receptor (GR). Using competitive
      receptor autoradiography, we show that Sprague Dawley male and female rat pups
      administered 1% carrageenan into the intraplantar surface of the hindpaw on the
      day of birth have significantly decreased CRFR1 binding in the basolateral
      amygdala and midbrain periaqueductal gray in adulthood. In contrast, CRFR2
      binding, which is associated with stress termination, was significantly increased
      in the lateral septum and cortical amygdala. GR expression, measured with in situ
      hybridization and immunohistochemistry, was significantly increased in the
      paraventricular nucleus of the hypothalamus and significantly decreased in the
      hippocampus of neonatally injured adults. In parallel, acute stress-induced
      corticosterone release was significantly attenuated and returned to baseline more
      rapidly in adults injured on PD0 in comparison to controls. Collectively, these
      data show that early life pain alters neural circuits that regulate responses to
      and neuroendocrine recovery from stress, and suggest that pain experienced by
      infants in the Neonatal Intensive Care Unit may permanently alter future
      responses to anxiety- and stress-provoking stimuli. 

PMID- 24094875
TI  - Thalamic neuropeptide mediating the effects of nursing on lactation and maternal
      motivation.
AB  - Nursing has important physiological and psychological consequences on mothers
      during the postpartum period. Tuberoinfundibular peptide of 39 residues (TIP39)
      may contribute to its effects on prolactin release and maternal motivation. Since
      TIP39-containing fibers and the receptor for TIP39, the parathyroid hormone 2
      receptor (PTH2 receptor) are abundant in the arcuate nucleus and the medial
      preoptic area, we antagonized TIP39 action locally to reveal its actions.
      Mediobasal hypothalamic injection of a virus encoding an antagonist of the PTH2
      receptor markedly decreased basal serum prolactin levels and the suckling-induced
      prolactin release. In contrast, injecting this virus into the preoptic area had
      no effect on prolactin levels, but did dampen maternal motivation, judged by
      reduced time in a pup-associated cage during a place preference test. In support
      of an effect of TIP39 on maternal motivation, we observed that TIP39 containing
      fibers and terminals had the same distribution within the preoptic area as
      neurons expressing Fos in response to suckling. Furthermore, TIP39 terminals
      closely apposed the plasma membrane of 82% of Fos-ir neurons. Retrograde tracer
      injected into the arcuate nucleus and the medial preoptic area labeled TIP39
      neurons in the posterior intralaminar complex of the thalamus (PIL), indicating
      that these cells but not other groups of TIP39 neurons project to these
      hypothalamic regions. We also found that TIP39 mRNA levels in the PIL markedly
      increased around parturition and remained elevated throughout the lactation
      period, demonstrating the availability of the peptide in postpartum mothers.
      Furthermore, suckling, but not pup exposure without physical contact, increased
      Fos expression by PIL TIP39 neurons. These results indicate that suckling
      activates TIP39 neurons in the PIL that affect prolactin release and maternal
      motivation via projections to the arcuate nucleus and the preoptic area,
      respectively. 

PMID- 24094876
TI  - TNF-alpha and its receptors modulate complex behaviours and neurotrophins in
      transgenic mice.
AB  - Tumour necrosis factor-alpha (TNF-alpha) plays an important role not only in
      immunity but also in the normal functioning of the central nervous system (CNS).
      At physiological levels, studies have shown TNF-alpha is essential to maintain
      synaptic scaling and thus influence learning and memory formation while also
      playing a role in modulating pathological states of anxiety and depression. TNF
      alpha signals mainly through its two receptors, TNF-R1 and TNF-R2, however the
      exact role that these receptors play in TNF-alpha mediated behavioural phenotypes
      is yet to be determined. METHODS: We have assessed TNF(-/-), TNF-R1(-/-) and TNF
      R2(-/-) mice against C57BL/6 wild-type (WT) mice from 12 weeks of age in order to
      evaluate measures of spatial memory and learning in the Barnes maze (BM) and Y
      maze, as well as other behaviours such as exploration, social interaction,
      anxiety and depression-like behaviour in a battery of tests. We have also
      measured hippocampal and prefrontal cortex levels of the neurotrophins nerve
      growth factor (NGF) and brain derived neurotrophic factor (BDNF) as well as used
      immunohistochemical analyses to measure number of proliferating cells (Ki67) and
      immature neurons (DCX) within the dentate gyrus. RESULTS: We have shown that
      young adult TNF(-/-) and TNF-R1(-/-) mice displayed impairments in learning and
      memory in the BM and Y-maze, while TNF-R2(-/-) mice showed good memory but slow
      learning in these tests. TNF(-/-)and TNF-R2(-/-) mice also demonstrated a
      decrease in anxiety like behaviour compared to WT mice. ELISA analyses showed
      TNF(-/-) and TNF-R2(-/-) mice had lower levels of NGF compared to WT mice.
      CONCLUSION: These results indicate that while lack of TNF-alpha can decrease
      anxiety-like behaviour in mice, certain basal levels of TNF-alpha are required
      for the development of normal cognition. Furthermore our results suggest that
      both TNF-R1 and TNF-R2 signalling play a role in normal CNS function, with
      knockout of either receptor impairing cognition on the Barnes maze.

PMID- 24094877
TI  - Serial transverse enteroplasty allows children with short bowel to wean from
      parenteral nutrition.
AB  - OBJECTIVE: To analyze the effects of serial transverse enteroplasty (STEP) on
      parenteral and enteral calories in children with short bowel syndrome, and
      examine short- and long-term complications. STUDY DESIGN: A retrospective
      analysis of prospectively-collected data from a large single center cohort of
      patients undergoing STEP procedure was analyzed. Baseline demographic and
      clinical information, operative data, and short- and long-term complications were
      recorded. Detailed growth and nutritional data were obtained for 6 months prior
      and 12 months following STEP procedure. RESULTS: Sixty-eight procedures were
      performed in 51 patients over a 68-month period. Median bowel length at first
      STEP was 51 cm with a median length gain of 54%. Repeat STEP patients had longer
      initial length (77 cm) and reduced length gain (20%). Operative times and blood
      loss were low, with few complications. Parenteral calorie requirement was stable
      or rising for 6 months prior to STEP, but decreased to median <20 kCal/kg/d at 1
      year postop. Longer length gains were associated with higher risk of stricture
      formation. Seven children were transplanted, and 60% of nontransplanted children
      were enterally independent, with the remainder making ongoing progress; 48/51
      children are alive at a median of 39 months follow-up. CONCLUSIONS: STEP is shown
      to be safe, well tolerated, and to have definitive benefit in reducing parenteral
      calorie requirements over the first year following the procedure. It has an
      important role in achieving enteral independence in children with short bowel
      syndrome.

PMID- 24094878
TI  - Height-independent estimation of glomerular filtration rate in children: an
      alternative to the Schwartz equation.
AB  - OBJECTIVE: To compare the diagnostic performance of 2 height-independent
      equations used to calculate estimated glomerular filtration rate (eGFR), those of
      Pottel (eGFR-Pottel) and the British Columbia Children's Hospital (BCCH) (eGFR
      BCCH), with the commonly used Schwartz equation (eGFR-Schwartz). STUDY DESIGN: We
      externally validated eGFR-Pottel and eGFR-BCCH in a well-characterized pediatric
      patient population (n = 152) and compared their diagnostic performance with that
      of eGFR-Schwartz using Bland-Altman analysis. All patients underwent glomerular
      filtration rate measurement using the gold standard single-injection inulin
      clearance method (GFR-inulin). RESULTS: Median GFR-inulin was 92.0 mL/min/1.73 m2
      (IQR, 76.1-107.4 mL/min/1.73 m2). Compared with GFR-inulin, the mean bias for
      eGFR-Schwartz was -10.1 mL/min/1.73 m(2) (95% limits of agreement [LOA], -77.5 to
      57.2 mL/min/1.73 m(2)), compared with -12.3 mL/min/1.73 m2 (95% LOA, -72.6 to
      47.9 mL/min/1.73 m(2)) for eGFR-Pottel and -22.1 mL/min/1.73 m2 (95% LOA, -105.0
      to 60.8 mL/min/1.73 m(2)) for eGFR-BCCH. eGFR-Pottel showed comparable accuracy
      to eGFR-Schwartz, with 77% and 76% of estimates within 30% of GFR-inulin,
      respectively. eGFR-BCCH was less accurate than eGFR-Schwartz (66% of estimates
      within 30% of GFR-inulin; P < .01). CONCLUSION: The performance of eGFR-Pottel is
      superior to that of eGFR-BCCH and comparable with that of eGFR-Schwartz. eGFR
      Pottel is a valid alternative to eGFR-Schwartz in children and could be reported
      by the laboratory if height data are not available.

PMID- 24094880
TI  - Unintentional pediatric exposures to central alpha-2 agonists reported to the
      National Poison Data System.
AB  - OBJECTIVE: To investigate national trends in unintentional pediatric exposures to
      3 common alpha-2 agonists: clonidine, guanfacine, and tizanidine. Secondary
      objectives were to describe outcomes, symptoms, treatments, and death. STUDY
      DESIGN: Retrospective chart review from the American Association of Poison
      Control Centers National Poison Data System from January 2000 to December 2011
      for unintentional exposure to clonidine, guanfacine, and tizanidine in children
      <= 12 years of age. RESULTS: From 2000-2011, there was a significant increase
      (5.9% per year, CI 3.6, 8.2) in unintentional pediatric exposures to National
      Poison Data System for central alpha-2 agonists. There were 27,825 clonidine
      exposures (67.3% male, median age: 4 years), 6143 guanfacine exposures (69.8%
      male, median age: 6 years), and 856 tizanidine exposures (51.9% male, median age:
      2 years). Guanfacine had the greatest proportional increase among the
      medications. Clonidine was associated with the most respiratory (799, 2.9%) and
      central nervous system symptoms (12,612, 45.3%), as well as the most episodes of
      bradycardia (2847, 10.2%) and hypotension (2365, 8.5%). Seven-hundred twenty
      eight (2.0%) patients were intubated, and 141 patients (0.5%) were administered
      vasopressors. There were 7 cardiac arrests and 3 deaths from clonidine.
      CONCLUSIONS: The number of unintentional pediatric exposures to alpha-2 agonists
      increased from 2000-2011. Clonidine exposures were the most commonly reported,
      more symptomatic, and associated with 3 deaths. Despite central nervous system
      depression, bradycardia, and hypotension being common, the need for intubation
      and vasopressors was rare.

PMID- 24094879
TI  - A randomized controlled trial of two nasal continuous positive airway pressure
      levels after extubation in preterm infants.
AB  - OBJECTIVE: To compare extubation failure rate with two ranges of nasal continuous
      positive airway pressure (NCPAP) in oxygen dependent preterm infants. STUDY
      DESIGN: Preterm infants of birth weight 500-1000 g and gestational age 23-30
      weeks, extubated for the first time during the first 6 weeks while requiring
      fraction of inspired oxygen >= 0.25, were randomly assigned to a NCPAP range of 4
      6 (low NCPAP) or 7-9 (high NCPAP) cmH2O. RESULTS: Infants were randomized to low
      (n = 47) or high NCPAP (n = 46) at day 16.3 +/- 14.7 and 15.5 +/- 12.4,
      respectively. Rates of extubation failure per criteria (24% vs 43%, P = .04, OR
      and 95% CI: 0.39 [0.16-0.96]) and re-intubation (17% vs 38%, P = .023, 0.33
      [0.016-0.85]) within 96 hours were significantly lower in the high- compared with
      the low NCPAP group. This was mainly due to a strikingly lower failure rate in
      the 500-750 g birth weight strata. Duration of ventilation, bronchopulmonary
      dysplasia, or severe bronchopulmonary dysplasia did not differ significantly. No
      infant developed pneumothorax during 96 hours post-extubation. CONCLUSIONS:
      Extubation failure in preterm infants with residual lung disease was lower with
      NCPAP range of 7-9 compared with 4-6 cmH2O. These findings suggest the need for
      higher distending pressure post-extubation in the more immature infants who are
      still oxygen dependent.

PMID- 24094881
TI  - Is the ongoing use of placebo in relapse-prevention clinical trials in
      schizophrenia justified?
AB  - BACKGROUND: Placebo-controlled randomised controlled trials (RCTs) continue to be
      required or recommended by regulatory authorities for the licensing of new drugs
      for schizophrenia, despite ongoing concerns regarding the risks to trial
      participants. METHODS: In this article we consider the scientific and ethical
      pros and cons associated with use of placebo in RCTs in schizophrenia,
      systematically review the published relapse-prevention placebo-controlled RCTs
      with second generation antipsychotics (SGAs) in schizophrenia, and examine the
      risks associated with these trials. RESULTS: We identified 12 studies involving
      2842 participants of which 968 received placebo. Relapse rates were 56% for
      placebo and 17.4% for active treatment groups. There is a lack of well-designed
      longitudinal studies investigating the psychosocial and biological consequences
      of exposure to placebo, to treatment discontinuation and to relapse in
      schizophrenia. CONCLUSION: In the absence of such studies it is risky to assume
      that patients are not at risk of significant distress and long-term harm, and
      therefore it is difficult to justify the ongoing use of placebo in relapse
      prevention RCTs in schizophrenia.

PMID- 24094883
TI  - Molecular genetic gene-environment studies using candidate genes in
      schizophrenia: a systematic review.
AB  - The relatively high heritability of schizophrenia suggests that genetic factors
      play an important role in the etiology of the disorder. On the other hand, a
      number of environmental factors significantly influence its incidence. As few
      direct genetic effects have been demonstrated, and there is considerable inter
      individual heterogeneity in the response to the known environmental factors,
      interactions between genetic and environmental factors may be important in
      determining whether an individual develops the disorder. To date, a considerable
      number of studies of gene-environment interactions (G*E) in schizophrenia have
      employed a hypothesis-based molecular genetic approach using candidate genes,
      which have led to a range of different findings. This systematic review aims to
      summarize the results from molecular genetic candidate studies and to review
      challenges and opportunities of this approach in psychosis research. Finally, we
      discuss the potential of future prospects, such as new studies that combine
      hypothesis-based molecular genetic candidate approaches with agnostic genome-wide
      association studies in determining schizophrenia risk. 

PMID- 24094884
TI  - A pilot double-blind comparison of d-serine and high-dose olanzapine in treatment
      resistant patients with schizophrenia.

PMID- 24094882
TI  - State-related functional integration and functional segregation brain networks in
      schizophrenia.
AB  - Altered topological properties of brain connectivity networks have emerged as
      important features of schizophrenia. The aim of this study was to investigate how
      the state-related modulations to graph measures of functional integration and
      functional segregation brain networks are disrupted in schizophrenia. Firstly,
      resting state and auditory oddball discrimination (AOD) fMRI data of healthy
      controls (HCs) and schizophrenia patients (SZs) were decomposed into spatially
      independent components (ICs) by group independent component analysis (ICA). Then,
      weighted positive and negative functional integration (inter-component networks)
      and functional segregation (intra-component networks) brain networks were built
      in each subject. Subsequently, connectivity strength, clustering coefficient, and
      global efficiency of all brain networks were statistically compared between
      groups (HCs and SZs) in each state and between states (rest and AOD) within
      group. We found that graph measures of negative functional integration brain
      network and several positive functional segregation brain networks were altered
      in schizophrenia during AOD task. The metrics of positive functional integration
      brain network and one positive functional segregation brain network were higher
      during the resting state than during the AOD task only in HCs. These findings
      imply that state-related characteristics of both functional integration and
      functional segregation brain networks are impaired in schizophrenia which
      provides new insight into the altered brain performance in this brain disorder. 

PMID- 24094885
TI  - Remembering one's ID/E-ntity: E/ID protein regulation of T cell memory.
AB  - Upon infection, CD8(+) T cells proliferate and differentiate into armed effector
      cells capable of eliminating the assaulting pathogen. Although the majority of
      the antigen-specific T cells will die as the immune response wanes, a few will
      survive indefinitely to establish the memory population and provide long-lived
      protection against reinfection. E protein transcription factors and their
      inhibitors, ID proteins, operate to balance expression of genes that control
      CD8(+) T cell differentiation through this process. Here, we discuss the role of
      ID2 and ID3 in promoting the generation and survival of effector and memory
      populations, particularly highlighting their reciprocal roles in shaping the
      CD8(+) T cell response unique to the inflammatory milieu. We further examine this
      coordinated control of gene expression in the context of additional transcription
      factors within the transcriptional network that programs CD8(+) effector and
      memory T cell differentiation. 

PMID- 24094886
TI  - DNMT3B7 expression related to MENT expression and its promoter methylation in
      human lymphomas.
AB  - DNA methyltransferase (DNMT) 3B7 is the most expressed DNMT3B splice variant. It
      was reported that the loss of DNMT3B function led to overexpression of the
      MEthylated in Normal Thymocyes (MENT) and accelerated mouse lymphomagenesis. We
      investigated the DNMT3B7 expression and its relationship to MENT expression and
      promoter methylation in human lymphomas. DNMT3B7 and MENT expression were
      significantly (p<0.0001, p<0.01) higher in lymphomas than in non-malignant.
      Expression of DNMT3B7 and MENT were associated with MENT promoter
      hypomethylation. DNMT3B7 overexpression might interfere with the normal DNA
      methylation mechanism required for silencing the MENT proto-oncogene, and may
      accelerate human lymphomagenesis.

PMID- 24094887
TI  - Dicer is down-regulated in clear cell renal cell carcinoma and in vitro Dicer
      knockdown enhances malignant phenotype transformation.
AB  - OBJECTIVES: Although emerging evidence has shown that the deregulation of micro
      ribonucleic acid (RNA) biogenesis machinery is involved in various human
      malignancies, this role has not been investigated in clear cell renal cell
      carcinoma (ccRCC). This study aims to determine whether Dicer, a key enzyme
      responsible for biogenesis of microRNA, is deregulated in ccRCC. The biological
      roles of Dicer in vitro are also determined. MATERIALS AND METHODS: The
      expression of Dicer at messenger RNA and protein levels was detected by real-time
      quantitative polymerase chain reaction and western blot, respectively, in human
      kidney tubule epithelial cell line, nonmetastatic 786-O ccRCC cell line, and
      metastatic ACHN ccRCC cell line, as well as in 42 cases of ccRCC surgical
      specimens including 14 cases with distant metastasis and their corresponding
      adjacent normal renal tissues. Dicer expression levels in specimens were also
      measured by immunohistochemical staining. Knockdown of Dicer expression in 786-O
      and ACHN ccRCC cell lines was achieved by transfecting short interfering RNA
      against Dicer. The effects of Dicer on cell proliferation, migration, and
      invasion were detected by 3-(4,5-dimethylthiazol-2-yl)-5-(3-carboxymethoxyphenyl)
      2-(4-sulfophenyl)-2H-tetrazolium, inner salt (MTS) assay, flow cytometric
      analyses, and Boyden chamber Transwell assay, respectively. RESULTS: Compared
      with human kidney tubule epithelial cell line, Dicer expression levels were
      significantly down-regulated in 786-O and ACHN ccRCC cell lines, with the
      metastatic ACHN ccRCC cell line having even lower levels. Meanwhile, Dicer
      expression levels were significantly down-regulated in ccRCC surgical specimens
      compared with adjacent normal renal tissues, with the metastatic ones further
      reduced, and Dicer messenger RNA levels were significantly correlated with
      overall tumor-node-metastasis stage of ccRCC. In vitro, the knockdown of Dicer
      significantly promoted cell proliferation, migration, and invasion. CONCLUSIONS:
      Reduced expression of Dicer may play a role in the tumorigenesis of ccRCC and
      further decline may be associated with distant metastasis of ccRCC.

PMID- 24094888
TI  - Localized hypertrophy of the semimembranosus muscle in a young athlete: a case
      report.
AB  - Popliteal fossa and distal thigh swellings have many causes in young active
      adult. Cysts are the main cause, but they may also evolve from fatty tissue,
      lymph nodes or the popliteal artery. Semimembranosus muscle hypertrophy, found in
      athletes and young active adults, is only rarely the main or only cause of
      swelling, and only four such cases are reported in the literature. The present
      article reports our experience in the management of a case of semimembranosus
      hypertrophy as the only cause of a swelling above the popliteal fossa, and its
      favorable evolution. 

PMID- 24094889
TI  - Free vascularized fibular graft as a salvage procedure for large clavicular
      defect: a two cases report.
AB  - The gold standard technique for treating clavicle non-union is based on cortico
      cancellous bone graft harvested from the iliac crest and fixed with a plate. In
      cases of large clavicular defects, this surgical procedure becomes ineffective
      and only reconstruction using vascularized bone grafts can be considered.
      Nevertheless, there are few reports in the literature dealing with this procedure
      and surgical technique remains unclear. We expose here a technique and results of
      free vascularized fibular graft for two patients with large clavicular defects.
      LEVELS OF EVIDENCE: Level IV, technical note.

PMID- 24094890
TI  - Distal quadricepsplasty in children: 88 cases of retractile fibrosis following
      intramuscular injections treated in Benin.
AB  - INTRODUCTION: Retractile fibrosis of the quadriceps (RFQ) is a physical and
      social handicap in children, and often results from a past history of quadriceps
      intramuscular injection. The aim of this study was to evaluate the therapeutic
      results of RFQ treated by distal quadricepsplasty using a modified Thompson-Payr
      procedure (DQPMTP). HYPOTHESIS: Functional recovery will be good with DQPMTP.
      PATIENTS AND METHODS: This is a descriptive retrospective 10-year study from 2002
      to 2011, including 74 children (88 knees) less than 15 years old, admitted for
      RFQ and treated in Benin. The types of RFQ were: knee flexion loss of motion 16
      cases (18.2%), lag of extension 54 cases (61.4%) and associated genu recurvatum,
      18 cases (20.5%). Wasting of the thigh was found in all cases. An associated
      distal femoral osteotomy was performed to correct a bone deformity in 18 cases
      (20.5%). RESULTS: There were 16 cases (18.2%) of poorly looking postoperative
      scars and 2 cases (2.3%) of fracture during physical therapy. Mean flexion ROM
      after surgery was 77.7 degrees . Mean flexion increased from 77.7 degrees  to
      108.5 degrees  following postoperative rehabilitation or a mean gain of 30.7
      degrees . The quadriceps muscle testing scores were at least 3/5. Results of
      DQPMTP were good in 80.7% of cases, as shown by mean active knee flexion of 108.5
      degrees  with normal active extension. The results were satisfactory in 17 cases
      (19.3%). DISCUSSION: DQPMTP has the advantage of cutting a minimum of blood
      vessels, thus limiting the risk of hematoma. Laterally placed incisions create
      less tension reducing the risk of skin necrosis. The clinical and radiological
      results of this series confirm those in the literature. Treatment of RFQ by
      DQPMTP provides satisfactory functional rehabilitation in patients, which
      confirms our hypothesis. LEVEL OF EVIDENCE: Level IV, retrospective study without
      comparison.

PMID- 24094891
TI  - Factors controlling the temporal and spatial variations in Synechococcus
      abundance in a monsoonal estuary.
AB  - Temporal and spatial variations in Synechococcus abundance were investigated over
      an annual cycle (February'10-January'11) along a salinity gradient (0-35) in the
      tropical Zuari estuary, influenced by south-west monsoons. Synechococcus
      exhibited salinity preferences with phycoerythrin-rich cells at salinities >2
      (Synechococcus-PEI), >20 (Synechococcus-PEII) and <1 (Synechococcus-PEIII)
      whereas phycocyanin-rich (Synechococcus-PC) dominant at lower salinities.
      Downstream stratification during monsoon caused Synechococcus group segregation
      in the surface and near-bottom waters. During monsoon-break and non-monsoon
      period stabilized waters, increased salinity, temperature, solar radiation and
      low rainfall favored high Synechococcus abundance whereas unstable waters,
      increased turbidity and low solar radiation during active monsoon lowered
      abundance. SYN-PC positively co-related with nitrate and phosphate and SYN-PEI
      with phosphate. Synechococcus contribution to phytoplankton carbon biomass ranged
      from 9 to 29%. In monsoonal estuaries, rainfall intensity regulates freshwater
      runoff which modulates the estuarine environment, creating temporal-spatial niche
      segregation of Synechococcus groups thereby serving as indicator organisms of the
      estuarine hydrodynamics. 

PMID- 24094892
TI  - Adaptation of marine plankton to environmental stress by glycolipid accumulation.
AB  - A systematic investigation of non-phosphorus containing glycolipids (GL) was
      conducted in the northern Adriatic Sea during two years at two stations with
      different nutrient loads. GL concentration varied both spatially and temporally,
      with values of 1.1-21.5 MUg/L and 0.4-44.7 MUg/L in the particulate and the
      dissolved fraction, respectively. The highest concentrations were measured during
      summer in surface waters and at the more oligotrophic station, where GL yields (%
      of total lipids) were often higher than 20% and 50% in the particulate and
      dissolved fractions, respectively. To obtain more insight into factors governing
      GL accumulation autotrophic plankton community structure (pico-, nano- and
      microplankton fractions), chlorophyll a, heterotrophic bacteria and nutrient
      concentrations were measured together with hydrographic parameters and sunlight
      intensity. During the investigated period smaller autotrophic plankton cells
      (pico- and followed by nanoplankton) prevailed in abundance over larger cells
      (microplankton), which were found in large numbers in freshened surface samples.
      Several major findings resulted from the study. Firstly, during PO4 limitation,
      particularly at the oligotrophic station, enhanced glycolipid instead of
      phospholipid accumulation takes place, representing an effective phosphate
      conserving mechanism. Secondly, results suggest that at seawater temperatures >19
      degrees C autotrophic plankton considerably accumulate GL, probably to achieve
      thermal stability. Thirdly, high sunlight intensities seem to influence increased
      GL accumulation; GL possibly plays a role in cell mechanisms that
      prevent/mitigate photooxidation. And finally, substantial accumulation of GL
      detected in the dissolved fraction could be related to the fact that GL do not
      contain biologically relevant elements, like phosphorus, which makes them an
      unattractive substrate for enzyme activity. Therefore, substantial portion of CO2
      could be removed from the atmosphere in P-limited regions during summer via its
      capture by plankton and conversion to GL.

PMID- 24094893
TI  - Tumour expresion of tissue factor and tissue factor pathway inhibitor in ovarian
      cancer- relationship with venous thrombosis risk.
AB  - INTRODUCTION: Ovarian cancer is known to display a particular association with
      venous thromboembolism (VTE) with reports up to 42% of patients developing
      thromboembolic complications. Tissue Factor (TF) and its inhibitor Tissue Factor
      Pathway Inhibitor (TFPI) have been implicated in VTE risk in cancer. The aim of
      this study was to measure tumour derived TF and TFPI and to investigate their
      potential role in VTE in ovarian cancer patients. METHODS: TF and TFPI mRNA
      expression was measured using TaqMan real time PCR in 99 ovarian tumour samples.
      Nineteen cases complicated by VTE were matched to 19 cases without VTE. TF and
      TFPI protein levels were measured using ELISA and immunohistochemistry was used
      to localize TF expression. The role of TF expression on overall survival was also
      determined. RESULTS: TF mRNA and protein expression was increased in tumours from
      patients with clear cell carcinoma (p<0.001). TF protein expression was also
      increased in endometroid carcinoma (P<0.01) compared with benign tumours. TFPI
      mRNA expression was increased in clear cell carcinoma (P<0.01). TF mRNA and
      antigen level was increased in malignant tumours of patients who developed VTE
      compared with matched malignant otumours of patients who remained thrombosis free
      (P<0.01). There was no difference in TFPI expression between the two groups.
      CONCLUSION: TF expression in ovarian cancer is significantly higher in patients
      who develop VTE. TF expression was increased in clear cell ovarian cancer and
      endometroid cancer and this may explain the higher risk of VTE in these
      subgroups. TF derived from these tumours may be the trigger for VTE in ovarian
      cancer.

PMID- 24094894
TI  - Vinorelbine, paclitaxel, etoposide, cisplatin, and cytarabine (VTEPA) is an
      effective second salvage therapy for relapsed/refractory Hodgkin lymphoma.
AB  - BACKGROUND: For Hodgkin lymphoma (HL) patients with refractory or relapsed (R/R)
      disease after primary therapy, the standard of care is a salvage regimen followed
      by autologous stem cell transplant (ASCT). However, patients who fail to respond
      to a salvage regimen have limited options. Our phase I study of cytarabine
      combined with fixed doses of vinorelbine, paclitaxel, etoposide, and cisplatin
      (VTEPA) for patients with R/R lymphoma showed an overall response rate (ORR) of
      33%. PATIENTS AND METHODS: To further examine the effectiveness of VTEPA, we
      conducted a retrospective review of 30 cases of R/R HL who received a salvage
      combination of VTEPA. RESULTS: This population included 15 men (50%), 18 stage
      III/IV (60%), and 14 with an International Prognostic Score >=3 (47%). The median
      number of previous regimens was 2 (range, 1-4), 19 patients (63%) received
      previous salvage therapy with ifosfamide, carboplatin, and etoposide. Twenty
      seven patients were evaluable for response. The most common Grade 3/4 toxicities
      were pancytopenia (19 patients, 97%), nausea/vomiting (17, 57%), fatigue (14,
      47%), and infection (6, 20%). Of the 27 patients evaluable for response, the ORR
      was 70% (7 complete response and 12 partial response). Twenty patients (66%) went
      on to ASCT and 1 patient underwent allogeneic transplant. With a median follow-up
      of 32 months, the median progression-free survival (PFS) and overall survival
      (OS) in patients who received transplantation after VTEPA were 28 and 38 months,
      respectively. CONCLUSION: Treatment with VTEPA for R/R HL is feasible with
      manageable side effects. With a high ORR, the PFS and OS for this group of
      patients suggest that VTEPA is a promising regimen for HL patients in whom
      previous lines of therapy have failed.

PMID- 24094895
TI  - Osteonecrosis of the jaw related to everolimus: a case report.
AB  - Antiresorptive agent-related osteonecrosis of the jaw results in appreciable
      morbidity in affected patients. Nowadays many physicians prescribe an
      antiangiogenic agent for the management of malignant metastases. Everolimus is a
      serine-threonine kinase that acts as an inhibitor of mammalian target of
      rapamycin, which results in reduced growth of cells, angiogenesis, and survival
      of cells. We report the first case to our knowledge of osteonecrosis of the jaw
      that seemed to result from the additive effect of everolimus. 

PMID- 24094896
TI  - Should we be giving bilateral inferior alveolar and lingual nerve blocks for
      third molar surgery?
AB  - Extraction of mandibular third molars is one of the most common procedures in
      oral and maxillofacial surgery, and it is normal practice to extract both teeth
      at one visit under general anaesthesia. However, when both teeth are extracted
      under local anaesthesia, bilateral inferior alveolar and lingual nerve blocks are
      required, which is a subject of debate among clinicians. Much of the controversy
      surrounds the safety and efficacy of bilateral anaesthesia even though many
      surgeons use local anaesthetic solutions for perioperative and postoperative pain
      relief after day case general anaesthesia with no reports of unwanted effects.
      The evidence presented in this review explores published research for and against
      the use of unilateral and bilateral inferior alveolar and lingual nerve blocks.

PMID- 24094897
TI  - Resting energy expenditure and the effects of muscle wasting in patients with
      chronic heart failure: results from the Studies Investigating Comorbidities
      Aggravating Heart Failure (SICA-HF).
AB  - OBJECTIVES: Muscle wasting is common in patients with chronic heart failure (HF)
      and worsens functional status. Protein catabolism is characteristic of muscle
      wasting and contributes to resting energy expenditure (REE). Glucagonlike peptide
      1 (GLP-1) is linked to REE in healthy individuals. We aimed to evaluate (1)
      whether REE is elevated in patients with HF with muscle wasting, and (2) whether
      basal GLP-1 levels are linked to REE in HF. DESIGN: Cross-sectional study.
      SETTING: Ambulatory patients with HF were recruited at the Charite Medical
      School, Campus Virchow-Klinikum, Berlin, Germany. PARTICIPANTS: A total of 166
      patients with HF and 27 healthy controls participating in the Studies
      Investigating Co-morbidities Aggravating Heart Failure (SICA-HF) were enrolled.
      GLP-1 was measured in 55 of these patients. MEASUREMENTS: Body composition was
      measured by dual-energy X-ray absorptiometry (DEXA). Muscle wasting was defined
      as appendicular lean mass of at least 2 SDs below values of a healthy young
      reference group. REE was measured by indirect calorimetry. GLP-1 was assessed by
      ELISA. RESULTS: Thirty-four of 166 patients (mean age 67.4 +/- 10.2 years, 77.7%
      male, New York Heart Association class 2.3 +/- 0.6) presented with muscle
      wasting. REE in controls and patients with muscle wasting was significantly lower
      than in patients without muscle wasting (1579 +/- 289 and 1532 +/- 265 vs 1748 +/
      359 kcal/d, P = .018 and P = .001, respectively). REE normalized for fat-free
      mass (FFM) using the ratio method (REE/FFM) and analysis of covariance was not
      different (P = .23 and .71, respectively). GLP-1 did not significantly correlate
      with REE (P = .49), even not after controlling for FFM using multivariable
      regression (P = .15). CONCLUSIONS: Differences in REE are attributable to lower
      FFM. GLP-1 does not relate to REE in patients with HF, possibly because of HF
      related effects on REE.

PMID- 24094898
TI  - Feasibility and acceptability of a delirium prevention program for cognitively
      impaired long term care residents: a participatory approach.
AB  - In this participatory action research study, researchers conducted a total of 3
      implementation cycles to evaluate the feasibility and acceptability of a new
      delirium prevention program (DPP) for cognitively impaired residents in long term
      care (LTC) settings. Researchers interviewed 95 health care staff to obtain
      feedback on their use of the DPP and then modified the DPP and tested the changes
      in the next implementation cycle. Our results indicated that the DPP was feasible
      and that health care staff would accept it under certain conditions. We found
      there were 4 keys to successful implementation of the DPP: support for the
      program from both the administration and the users; effective clinician
      leadership to ensure proper delivery of the DPP (format, content and values) and
      its appropriate adaptation to the LTC facility's internal culture and policies; a
      sense of ownership among the DPP users; and, last, practical hands-on training as
      well as theoretical training for staff. 

PMID- 24094899
TI  - Providing long term care for sex offenders: liabilities and responsibilities.
AB  - The high risk for recidivism among sex offenders who need long term care (LTC)
      raises serious issues when they are cared for alongside frail, vulnerable adults.
      LTC providers must balance offenders' right to access care with other residents'
      right to be free from abuse and must assess and manage the risks associated with
      admitting offenders. This article identifies sources of legal liability that
      derive from sex offender management and discusses the need for the LTC community
      to develop reasonable, balanced guidance on how best to mitigate the risks
      associated with sex offenders, protect the rights of all residents, and reduce
      provider liabilities. 

PMID- 24094900
TI  - Staffing, quality, and productivity in the nursing home.

PMID- 24094901
TI  - Use and perceived benefits of mobile devices by physicians in preventing adverse
      drug events in the nursing home.
AB  - OBJECTIVE: Although mobile devices equipped with drug reference software may help
      prevent adverse drug events (ADEs) in the nursing home (NH) by providing
      medication information at the point of care, little is known about their use and
      perceived benefits. The goal of this study was to conduct a survey of a
      nationally representative sample of NH physicians to quantify the use and
      perceived benefits of mobile devices in preventing ADEs in the NH setting.
      DESIGN/SETTING/PARTICIPANTS: We surveyed physicians who attended the 2010
      American Medical Directors Association Annual Symposium about their use of mobile
      devices, and beliefs about the effectiveness of drug reference software in
      preventing ADEs. RESULTS: The overall net valid response rate was 70% (558/800)
      with 42% (236/558) using mobile devices to assist with prescribing in the NH.
      Physicians with 15 or fewer years of clinical experience were 67% more likely to
      be mobile device users, compared with those with more than 15 years of clinical
      experience (odds ratio = 1.68; 95% confidence interval = 1.17-2.41; P = .005).
      For those who used a mobile device to assist with prescribing, almost all (98%)
      reported performing an average of 1 or more drug look-ups per day, performed an
      average of 1 to 2 lookups per day for potential drug-drug interactions (DDIs),
      and most (88%) believed that drug reference software had helped to prevent at
      least 1 potential ADE in the preceding 4-week period. CONCLUSIONS: The proportion
      of NH physicians who use mobile devices with drug reference software, although
      significant, is lower than in other clinical environments. Our results suggest
      that NH physicians who use mobile devices equipped with drug reference software
      believe they are helpful for reducing ADEs. Further research is needed to better
      characterize the facilitators and barriers to adoption of the technology in the
      NH and its precise impact on NH ADEs.

PMID- 24094902
TI  - Association of c-Met phosphorylation with micropapillary pattern and small
      cluster invasion in pT1-size lung adenocarcinoma.
AB  - Lung adenocarcinomas with micropapillary pattern (MPP) are associated with
      frequent nodal metastasis. However, little is known about the mechanisms that
      underlie MPP-associated nodal metastasis. We have previously reported that pT1
      lung adenocarcinomas with MPP are significantly associated with small cluster
      invasion (SCI) and lymphatic involvement. SCI is defined as markedly resolved
      acinar-papillary tumor structures with single or small clusters of carcinoma
      cells invading stroma within fibrotic foci. In this study, we hypothesized that c
      Met activation may be involved in the MPP-SCI sequence, given that the c-Met
      tyrosine-kinase receptor and its ligand hepatocyte growth factor (HGF), play
      important roles in tumor cell motility and invasion. We analyzed 125 pT1-size
      lung adenocarcinomas for immunohistochemical expression of phosphorylated c-Met
      and its correlation with MPP, SCI, lymphatic involvement and prognosis. SCI was
      significantly more frequent in the MPP-positive group (P<0.0001) and associated
      with lymphatic involvement (P<0.0001) and nodal metastasis (P=0.021). c-Met
      protein was detected in all tumors by immunohistochemistry as membranous and
      cytoplasmic staining. Phospho-c-Met (pc-Met) was positive in 119/125 tumors (95%)
      and expressed at high levels in 27 cases (22%). A high level of pc-Met expression
      was significantly associated with MPP (P=0.01) and SCI (P=0.0059). Moreover, in
      tumors with MPP or SCI, those expressing high levels of pc-Met were significantly
      more associated with lymphatic involvement. In p-Stage IA lung adenocarcinomas
      (n=99), patients in the high pc-Met expression group showed significantly worse
      survival than patient in the low expression group (P=0.0313). These results
      suggest that activation of c-Met through phosphorylation may be involved in MPP
      and SCI. 

PMID- 24094903
TI  - Five-year results for endovascular repair of acute complicated type B aortic
      dissection.
AB  - INTRODUCTION: Despite a current lack of U.S. Food and Drug Administration
      approval for the indication, thoracic endovascular aortic repair (TEVAR) has
      replaced open surgical management for acute complicated type B aortic dissection
      due to promising short- and midterm data. However, long-term results, with a view
      toward durability and need for secondary procedures, are limited. As such, the
      objective of the present study is to report long-term outcomes of TEVAR for acute
      (<= 2 weeks from symptom onset) complicated type B dissection. METHODS: Between
      July 2005 and September 2012, 50 consecutive patients underwent TEVAR for
      management of acute complicated type B dissection at a single referral
      institution. Patient records were retrospectively reviewed from a prospectively
      maintained clinical database. RESULTS: Indications for intervention included
      rupture in 10 (20%), malperfusion in 24 (48%), and/or refractory pain/impending
      rupture in 17 (34%). One patient (2%) had both rupture and malperfusion
      indications. Ten (20%) patients required one or more adjunctive procedures, in
      addition to TEVAR, to treat malperfusion syndromes. In-hospital and 30-day rates
      of death were both 0%; 30-day/in-hospital rates of stroke, permanent
      paraplegia/paraparesis, and new-onset dialysis were 2% (n = 1), 2% (n = 1), and
      4% (n = 2), respectively. Median follow-up was 33.8 months [interquartile range,
      12.3-56.6 months]. Overall survival at 5 and 7 years was 84%, with no deaths
      attributable to aortic pathology. Thirteen (26%) patients required a total of 17
      reinterventions over the study period for type I endoleak (n = 5), metachronous
      aortic pathology (n = 5), persistent false lumen pressurization via distal
      fenestrations (n = 4), type II endoleak (n = 2), or retrograde acute type A
      aortic dissection (n = 1). Median time to first reintervention was 4.5 months
      (range, 0 days-40.3 months). Of the 17 total reinterventions, six (35%) were
      performed using open techniques and 11 (65%) with endovascular or hybrid methods;
      there was no difference in survival between patients who did or did not require
      reintervention. CONCLUSIONS: This study confirms the excellent short-term
      outcomes of TEVAR for acute complicated type B dissection and demonstrates the
      results to be durable and sustained over long-term follow-up. Although aortic
      reinterventions were required in one-quarter of patients, no aortic-related
      deaths were observed. These data support the use of TEVAR for acute complicated
      type B aortic dissection but also highlight the importance of life-long aortic
      surveillance by an experienced aortic referral center in order to identify and
      treat complications of the underlying disease process and treatment, as well as
      new aortic pathologies, as they arise.

PMID- 24094904
TI  - Miller Fisher syndrome with positivity of anti-GAD antibodies.

PMID- 24094905
TI  - Flat epithelial atypia: comparison between 9-gauge and 11-gauge devices.
AB  - BACKGROUND: This study aimed to establish if women with a diagnosis of flat
      epithelial atypia (FEA) without residual microcalcifications at stereotactic
      vacuum-assisted breast biopsy (VABB) could be managed with mammographic follow-up
      (FU) instead of surgery and to compare 9-gauge and 11-gauge devices. PATIENTS AND
      METHODS: From October 2003 to January 2011, 2382 VABB procedures were performed
      (1373 with 11-gauge and 1009 with 9-gauge). We found 121 cases of pure FEA that
      were surgically treated: 57 with a 9-gauge device (group 1) and 64 with an 11
      gauge device (group 2). The underestimation rate (UR) of malignancy for patients
      without and those with residual microcalcifications for each VABB device was
      calculated. Differences between groups were analyzed with the Fischer exact test.
      RESULTS: The overall UR of FEA was 4% (2 of 57) with the 9-gauge device and 8% (5
      of 64) with the 11-gauge device. With a 9-gauge device, the UR for patients
      without residual microcalcifications was 0% (0 of 46), and the UR for patients
      with residual microcalcifications was 18% (2 of 11). With an 11-gauge device, the
      UR for patients without residual microcalcifications was 0% (0 of 39), the UR for
      patients with residual microcalcifications at post-biopsy mammograms was 16% (5
      of 25). With a 9-gauge device, 80% (46 of 57) of patients did not have residual
      microcalcifications after VABB. With an 11-gauge device, 60% (39 of 64) of
      patients had no residual microcalcifications after VABB. Differences between the
      9-gauge and 11-gauge devices were statistically significant (P < .05).
      CONCLUSION: Women with FEA without residual microcalcifications after VABB can be
      managed conservatively. Nine-gauge VABB is associated with a lower percentage of
      residual microcalcifications compared with an 11-gauge device, but it is safe to
      follow patients with FEA if all calcifications are removed with the core biopsy.

PMID- 24094906
TI  - Clinical findings and electrodiagnostic testing in 108 consecutive cases of
      lumbosacral radiculopathy due to herniated disc.
AB  - STUDY AIM: This prospective study aim to examine whether clinical findings and
      electrodiagnostic testing (EDX) in patients with lumbosacral monoradiculopathy
      due to herniated disc (HD) differ as a function of root involvement level (L5 vs.
      S1) and HD zone (paramedian vs. intraforaminal). PATIENTS AND METHODS: All
      patients with L4, L5 or S1 monoradiculopathy were prospectively enrolled at four
      electromyography (EMG) labs over a 2-year period. The diagnosis was based on a
      congruence between patient history and MRI evidence of HD. We compared the
      sensitivities of clinical findings and EDX with respect to both root involvement
      level and HD zone. Multivariate logistic regression was performed in order to
      verify the association between abnormal EMG, clinical, and neuroradiological
      findings. RESULTS: One hundred and eight patients (mean age 47.7 years, 55% men)
      were consecutively enrolled. Sensory loss in the painful dermatome was the most
      frequent finding at physical examination (56% of cases). EMG was abnormal in at
      least one muscle supplied by femoral and sciatic nerves in 45 cases (42%).
      Inclusion of paraspinal muscles increased sensitivity to only 49% and that of
      proximal muscles was useless. Motor and sensory neurography was seldom abnormal.
      The most frequent motor neurographic abnormalities were a delay of F-wave minimum
      latency and decrease in the compound muscle action potential amplitude from
      extensor digitorum brevis and abductor hallucis in L5 and S1 radiculopathies,
      respectively. Sensory neurography was usually normal, the amplitude of sensory
      nerve action potential was seldom reduced when HD injured dorsal root ganglion or
      postganglionic root fibres. Multivariate logistic regression analysis showed that
      EMG abnormalities could be predicted by myotomal muscular weakness, abnormal deep
      reflexes, and paraesthesiae. The only clinical and electrophysiological
      differences with respect to root involvement level concerned deep reflexes and
      motor neurography of deep peroneal and tibial nerves. CONCLUSIONS: Only some EDX
      parameters are helpful for the diagnosis of lumbosacral radiculopathy. EMG was
      abnormal in less than 50% of cases and its abnormalities could be predicted by
      some clinical findings. However, neurography is useful as a tool for differential
      diagnosis between radiculopathy and more diffuse disorders of the peripheral
      nervous system (polyneuropathy, plexopathy).

PMID- 24094907
TI  - A comparison of recording modalities of P300 event-related potentials (ERP) for
      brain-computer interface (BCI) paradigm.
AB  - AIMS OF THE STUDY: A brain-computer interface aims at restoring communication and
      control in severely disabled people by identification and classification of EEG
      features such as event-related potentials (ERPs). The aim of this study is to
      compare different modalities of EEG recording for extraction of ERPs. The first
      comparison evaluates the performance of six disc electrodes with that of the
      EMOTIV headset, while the second evaluates three different electrode types (disc,
      needle, and large squared electrode). MATERIAL AND METHODS: Ten healthy
      volunteers gave informed consent and were randomized to try the traditional EEG
      system (six disc electrodes with gel and skin preparation) or the EMOTIV Headset
      first. Together with the six disc electrodes, a needle and a square electrode of
      larger surface were simultaneously recording near lead Cz. Each modality was
      evaluated over three sessions of auditory P300 separated by one hour. RESULTS: No
      statically significant effect was found for the electrode type, nor was the
      interaction between electrode type and session number. There was no statistically
      significant difference of performance between the EMOTIV and the six traditional
      EEG disc electrodes, although there was a trend showing worse performance of the
      EMOTIV headset. However, the modality-session interaction was highly significant
      (P<0.001) showing that, while the performance of the six disc electrodes stay
      constant over sessions, the performance of the EMOTIV headset drops dramatically
      between 2 and 3h of use. Finally, the evaluation of comfort by participants
      revealed an increasing discomfort with the EMOTIV headset starting with the
      second hour of use. CONCLUSION: Our study does not recommend the use of one
      modality over another based on performance but suggests the choice should be made
      on more practical considerations such as the expected length of use, the
      availability of skilled labor for system setup and above all, the patient
      comfort.

PMID- 24094908
TI  - Concomitant changes in clinical and posturographic data in elderly fallers during
      the course of an in-home anti-falling multimodal program--a preliminary
      investigation.
AB  - AIM OF THE STUDY: The objective of this preliminary study was to evaluate the
      effectiveness, in terms of fall reduction, of an in-home strategy that we have
      developed for elderly fallers. We also aimed at finding links between the
      expected changes in the data obtained in static posturography and in clinical
      balance tests through our program. PATIENTS AND METHODS: Twelve elderly patients
      living at home who were diagnosed as fallers (5 males and 7 females; 77.9+/-4.1
      years) participated in the study. Our multimodal intervention lasted 6 months.
      Before this period, and one year later, an evaluation was conducted using
      cognitive (MMSE), clinical balance tests (i.e. Berg Balance Scale, Balance One
      leg, Timed Up and Go, and Functional Reach tests) and static posturography (where
      the area of body sway, velocity and medio-lateral and antero-posterior amplitudes
      were recorded twice, first with eyes open and then with eyes closed). RESULTS:
      Among the 12 patients who were diagnosed as fallers, eight became non-fallers.
      When comparing data obtained after the intervention with those obtained
      beforehand, we found significant changes in all of the clinical balance tests and
      in the posturographic-derived variables indicating improvements in the balance
      control in our group of subjects. We also found significant correlations between
      the changes in the Berg Balance Scale scores and the changes in the area of body
      sway data, in antero-posterior amplitude both with eyes open and with eyes
      closed, and also in the medio-lateral amplitude in the eyes closed condition.
      CONCLUSIONS: We prospectively demonstrated the relevance of our anti-falling
      intervention at home and of the use of posturography for clinical follow-up.

PMID- 24094909
TI  - Achilles tendon vibration shifts the center of pressure backward in standing and
      forward in sitting in young subjects.
AB  - OBJECTIVE: An Achilles tendon (AT) vibration is known to disrupt the postural
      control in standing ("vibration-induced falling", VIF) and to backward tilt the
      postural vertical in restrained sitting position, suggesting a link between AT
      vibration and internal representations involved in postural control. A
      recalibration of some troubles in body orientation by oriented sensory
      manipulations could be of great clinical interest. In order to use the VIF
      paradigm in a procedure suitable for a rehabilitation context, AT vibration
      deserves to be more investigated in sitting, for security reasons, and first in
      young participants. METHOD: In 12 healthy participants (6 men/6 women; 23.3+/-1.9
      years), posturographic data to AT vibrations (85 Hz) were recorded over 30 s
      standing and 40 s sitting trials. RESULTS: Surprisingly, four types of
      differences were found between standing and sitting AT vibrations:
      presence/absence of VIF and kinesthetic illusion, opposite directions of the
      centre of foot pressure (CoP) displacements, different temporal profiles. In
      standing: VIF without kinesthetic illusion, rapid backward shift of CoP with a
      peak of -54.6+/-11.3 mm (with respect to baseline P<0.001) 2.8+/-0.2 s after
      vibration onset. In sitting: surprising systematic forward shift of the CoP
      throughout the duration of AT vibration with a maximum of 27.9+/-18.9 mm (P<0.05
      with respect to the baseline) 19.6+/-0.3 s after vibration onset, associated with
      a kinesthetic illusion in most subjects. CONCLUSION: The present study
      invalidates our idea to extend in sitting the VIF paradigm but the unexpected
      results open a new window about the basic mechanisms underlying muscle vibration
      effects.

PMID- 24094910
TI  - Optimal parameters of transcranial electrical stimulation for intraoperative
      monitoring of motor evoked potentials of the tibialis anterior muscle during
      pediatric scoliosis surgery.
AB  - OBJECTIVE: Transcranial electric stimulation elicited muscle motor evoked
      potentials (TESmMEPs) is one of the best methods for corticospinal tract's
      function monitoring during spine and spinal cord surgeries. A train of multipulse
      electric stimulation is required for eliciting TESmMEPs under general
      anaesthesia. Here, we investigated the best stimulation parameters for eliciting
      and recording tibialis anterior's TESmMEPs during paediatric scoliosis surgery.
      PATIENTS AND METHODS: Numbers of pulses (NOP), inter-stimulus intervals (ISI) and
      current intensities allowing the best size tibialis anterior muscle's TESmMEPs
      under general anaesthesia, were tested and collected during 77 paediatric
      scoliosis surgery monitoring procedures in our hospital. Individual pulse
      duration was kept at 0.5 ms and stimulating electrodes were positioned at C1 and
      C2 (International 10-20-EEG-System) during all the tests. RESULTS: The NOP used
      for eliciting the best tibialis anterior TESmMEPs response was 5, 6, and 7
      respectively in 21 (27%), 47 (61%) and 9 (12%) out of the 77 patients. The ISI
      was 2, 3 and 4 ms respectively in 13 (17%), 55 (71%) and 9 (12%) of them. The
      current intensity used varied from 300 to 700 V (mean: 448+/-136 V). CONCLUSION:
      Most patients had 6 as best NOP (61%) and 3 ms as best ISI (71%). These findings
      support that a NOP of 6 and an ISI of 3 ms should be preferentially used as
      optimal stimulation settings for intraoperative tibialis anterior muscle's
      TESmMEPs eliciting and recording during paediatric scoliosis surgery.

PMID- 24094911
TI  - Effects of repetitive peripheral magnetic stimulation on normal or impaired motor
      control. A review.
AB  - INTRODUCTION: Repetitive magnetic stimulation at the periphery (rPMS), i.e. over
      spinal roots, nerves or muscles, represents a new painless and noninvasive
      approach that can contribute to motor recovery. This method is based on the
      assumption that, under rPMS, neural networks involved in motor control would be
      regulated by the large recruitment of proprioceptive afferents, with little
      activation of cutaneous receptors. STUDY AIM: This literature review dealing with
      rPMS after-effects on motor control aimed at better understanding the outcome
      measures and further discussing some possible involved mechanisms. RESULTS: Our
      literature search resulted in 13 studies that used different types of outcomes
      (neurophysiological, biomechanical, clinical) to test the influence of rPMS over
      spinal roots or muscles in healthy individuals and in persons with stroke or
      spinal disorders. Dynamic changes were reported post-rPMS, such as spasticity
      reduction and improvements of movement dynamics. Studies also brought about some
      interesting insights on the cortical plasticity associated with rPMS effects,
      such as the activation of fronto-parietal loops that may explain the post-rPMS
      improvement of motor planning. CONCLUSIONS: Due to the heterogeneous and scant
      literature on the topic, no conclusion can be drawn to date. However, the results
      encourage the concurrent testing of clinical, neurophysiological and
      biomechanical outcomes to investigate more precisely the relevance of rPMS in
      neurological rehabilitation.

PMID- 24094912
TI  - Biomarker tests for the diagnosis of Alzheimer's disease: Generating evidence to
      inform insurance coverage determinations.
AB  - Outside of their uses in drug development and clinical research trials, the
      current clinical value of performing any type of formal biomarker testing for the
      diagnosis or exclusion of Alzheimer's disease (AD) is controversial, and most
      biomarker tests for AD are not covered by public or private insurers. This
      situation raises the issue of how insurers determine whether there is "adequate"
      evidence to justify a positive coverage determination in this area. This article,
      a focused condensation of a larger white paper, is the product of an initiative
      led by the Institute for Clinical and Economic Review to convene a multiple
      stakeholder AD Diagnostics Policy Development Group composed of patient
      advocates, clinicians, clinical researchers, manufacturers, and insurers. The
      larger white paper was the basis for the evidence review presented to the
      Medicare Evidence Development and Coverage Advisory Committee meeting on January
      30, 2013, as part of its deliberations on positron emission tomography-amyloid
      imaging. Herein we focus on the description of the core elements of what insurers
      will be looking for in evidence on all potential diagnostic tests for AD.
      Corresponding research recommendations are also included, framed to serve as a
      guide for future AD diagnostics research. 

PMID- 24094914
TI  - Discussion.

PMID- 24094913
TI  - Targeting of the Hedgehog signal transduction pathway suppresses survival of
      malignant pleural mesothelioma cells in vitro.
AB  - OBJECTIVE: The present study sought to determine whether the Hedgehog (Hh)
      pathway is active and regulates the cell growth of cultured malignant pleural
      mesothelioma (MPM) cells and to evaluate the efficacy of pathway blockade using
      smoothened (SMO) antagonists (SMO inhibitor GDC-0449 or the antifungal drug
      itraconazole [ITRA]) or Gli inhibitors (GANT61 or the antileukemia drug arsenic
      trioxide [ATO]) in suppressing MPM viability. METHODS: Selective knockdown of SMO
      to inhibit Hh signaling was achieved by small interfering RNA in 3 representative
      MPM cells. The growth inhibitory effect of GDC-0449, ITRA, GANT61, and ATO was
      evaluated in 8 MPM lines, with cell viability quantified using the 3-(4,5
      dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay. Cell death was
      determined by annexinV/propidium iodide staining and flow cytometry. RESULTS: SMO
      small interfering RNA mediated a two- to more than fivefold reduction of SMO and
      Gli1 gene expression as determined by real-time quantitative reverse
      transcriptase polymerase chain reaction, indicating significant Hh pathway
      blockade. This was associated with significantly reduced cell viability (34% +/-
      7% to 61% +/- 14% of nontarget small interfering RNA controls; P = .0024 to P =
      .043). Treating MPM cells with Hh inhibitors resulted in a 1.5- to 4-fold
      reduction of Gli1 expression. These 4 Hh antagonists strongly suppressed MPM cell
      viability. More importantly, ITRA, ATO, GANT61 induced significant apoptosis in
      the representative MPM cells. CONCLUSIONS: Hh signaling is active in MPM and
      regulates cell viability. ATO and ITRA were as effective as the prototypic SMO
      inhibitor GDC-0449 and the Gli inhibitor GANT61 in suppressing Hh signaling in
      MPM cells. Pharmaceutical agents Food and Drug Administration-approved for other
      indications but recently found to have anti-Hh activity, such as ATO or ITRA,
      could be repurposed to treat MPM.

PMID- 24094916
TI  - Discussion.

PMID- 24094915
TI  - Outcomes of surgical aortic valve replacement in moderate risk patients:
      implications for determination of equipoise in the transcatheter era.
AB  - OBJECTIVE: To determine the contemporary outcomes of surgical aortic valve
      replacement (SAVR) in a moderate surgical risk population. METHODS: We studied
      502 consecutive adults who had undergone isolated SAVR from January 2002 to June
      2011 for severe aortic valve stenosis with a Society of Thoracic Surgery
      predicted risk of mortality of 4% to 8%. We included concomitant coronary artery
      bypass and aortic annular enlargement but not other concomitant procedures. The
      updated Valve Academic Research Consortium definitions were used, as appropriate.
      RESULTS: The median age was 80 years (range, 49-96), 323 (64.3%) had New York
      Heart Association class III-IV symptoms, and 101 (20.1%) had undergone previous
      coronary artery bypass grafting. The mean predicted risk of mortality was 5.6%.
      Concomitant coronary artery bypass grafting was performed in 270 (53.8%). Re
      exploration for bleeding occurred in 29 (5.8%), stroke in 9 (1.8%), and vascular
      complications in 2 (0.4%). In the cohort, 14 early deaths (2.8%) occurred. During
      follow-up (1174 days), 175 patients died. Using multivariate logistic regression
      analysis, the significant independent predictors of mid-term death included
      chronic pulmonary disease (hazard ratio, 2.00, 95% confidence interval, 1.41
      2.84; P < .001), peripheral vascular disease (hazard ratio, 1.58; 95% confidence
      interval, 1.05-2.37; P = .029), and atrial fibrillation (hazard ratio, 1.75; 95%
      confidence interval, 1.16-2.65; P = .008). CONCLUSIONS: SAVR in moderate-risk
      patients is currently performed with one half of the early predicted risk (2.8%)
      and a low likelihood of complications, including a 1.8% incidence of stroke.
      Patients counseled for randomization to transcatheter aortic valve insertion
      should be informed of the excellent early to mid-term outcomes of SAVR,
      particularly those without pulmonary impairment, peripheral vascular disease, or
      atrial fibrillation.

PMID- 24094917
TI  - Caveats of smartphone applications for the cardiothoracic trainee.
AB  - BACKGROUND: The clinical environment is becoming increasingly dominated by
      information technology, most recently the smartphone with its applications (apps)
      of a multitude of uses. There are already tens of thousands of medical apps
      available for download, to educate both patients and trainees, and many more are
      being designed to facilitate delivery of care. The rapid development of this
      technology has outgrown its quality evaluation and regulation, both urgently
      required to maintain patient safety, protect sensitive data, and ensure
      dissemination of accurate information. We review medical apps themed towards
      cardiothoracic surgery in terms of medical professional involvement in their
      content and design. METHODS: iTunes and Play Store were searched for
      cardiothoracic surgery-themed medical apps, using the terms cardiothoracic,
      thoracic, cardiac, heart, lung, surgery, and variations thereof and including the
      term medical. RESULTS: A focused search yielded 379 apps, of which 6% were
      associated with a named medical professional, 15% with a publisher or
      professional society, and 63% with a user rating. CONCLUSIONS: The findings
      suggest inadequate input from the medical profession. The article discusses the
      pressing issues regarding quality evaluation, regulation, and information
      security, required for smartphones and handheld devices to become an integral and
      safe part of delivery of care.

PMID- 24094918
TI  - Synthesis of iron-based nanoparticles using oolong tea extract for the
      degradation of malachite green.
AB  - Iron-based nanoparticles (OT-FeNP) were synthesized using oolong tea extracts.
      Their morphology, structure and size were confirmed by scanning electron
      microscopy (SEM), X-ray energy-dispersive spectroscopy (EDS), X-ray diffraction
      (XRD), UV-visible (UV-vis) and Fourier Transform Infrared spectroscopy (FTIR).
      Formation of FeNP results in mostly spherical particles with diameters ranging
      from 40 to 50 nm. Degradation of malachite green (MG) using OT-FeNP demonstrated
      that kinetics fitted well to the pseudo first-order reaction by removing 75.5% of
      MG (50 mg/L). This indicated that OT-FeNP has the potential to serve as a green
      nanomaterial for environmental remediation.

PMID- 24094919
TI  - Patient-physician colorectal cancer screening discussion content and patients'
      use of colorectal cancer screening.
AB  - OBJECTIVE: The US Preventive Services Task Force recommends using the 5As (i.e.,
      Assess, Advise, Agree, Assist and Arrange) when discussing preventive services.
      We evaluate the association of the 5As discussion during primary care office
      visits with patients' subsequent colorectal cancer (CRC) screening use. METHODS:
      Audio-recordings of n=443 periodic health exams among insured patients aged 50-80
      years and due for CRC screening were joined with pre-visit patient surveys and
      screening use data from an electronic medical record. Association of the 5As with
      CRC screening was assessed using generalized estimating equations. RESULTS: 93%
      of patients received a recommendation for screening (Advise) and 53% were
      screened in the following year. The likelihood of screening increased as the
      number of 5A steps increased: compared to patients whose visit contained no 5A
      step, those whose visit contained 1-2 steps (OR=2.96 [95% CI 1.16, 7.53]) and 3
      or more steps (4.98 [95% CI 1.84, 13.44]) were significantly more likely to use
      screening. CONCLUSIONS: Physician CRC screening recommendations that include
      recommended 5A steps are associated with increased patient adherence. PRACTICE
      IMPLICATIONS: A CRC screening recommendation (Advise) that also describes patient
      eligibility (Assess) and provides help to obtain screening (Assist) may lead to
      improved adherence to CRC screening.

PMID- 24094920
TI  - Trends in use of electronic nicotine delivery systems by adolescents.
AB  - Electronic nicotine delivery systems (ENDS) have been gaining in popularity. The
      few prevalence studies in adults have found that most ENDS users are current or
      former smokers. The objectives of this study were to estimate the prevalence of
      ENDS usage in adolescents, and examine the correlates of use. Self-administered
      written surveys assessing tobacco use behaviors were conducted in multiple waves
      as part of a larger intervention study in two large suburban high schools. The
      prevalence of past-30 day ENDS use increased from 0.9% in February 2010 to 2.3%
      in June 2011 (p=0.009). Current cigarette smokers had increased odds of past-30
      day ENDS use in all study waves. When adjusted for school, grade, sex, race and
      smoking status, students in October 2010 (Adjusted OR 2.12; 95% confidence
      interval (CI): 1.12-4.02) and June 2011 (Adjusted OR 2.51; 95% CI: 1.17-4.71) had
      increased odds past-30 day ENDS use compared to February 2010. The prevalence of
      ENDS use doubled in this sample of high school students, and current cigarette
      smoking is the strongest predictor of current use. Continued monitoring of ENDS
      is needed to determine whether it increases the likelihood of cigarette smoking
      initiation and maintenance in youth.

PMID- 24094921
TI  - Integrating smoking cessation into substance use disorder treatment for military
      veterans: measurement and treatment engagement efforts.
AB  - Military personnel and veterans smoke at higher rates than the general
      population, compromising physical performance readiness and health (Committee on
      Smoking Cessation in Military and Veteran Populations & Institute of Medicine,
      2009). While efforts are being made within both the Department of Defense and the
      Veterans' Administration (VA) hospitals to prevent onset, change the smoking
      culture, and promote smoking cessation; smoking rates are increasing among combat
      deployed service members, and smoking rates are particularly high among veterans
      with mental health and other substance use disorders (McFall, 2006). Recent
      research supports making smoking cessation widely available and integrated with
      other forms of care (Gierisch et al., 2012; McFall et al., 2010). This paper
      describes the efforts of one VA substance use disorder (SUD) treatment program to
      integrate smoking cessation in routine care, including assessment of tobacco use
      and motivation and intention to quit via the proposed Nic-BAM assessment. Our
      team was 100% successful in incorporating the Nic-BAM into our regular assessment
      of treatment program participants. This suggests that staff members are amenable
      to assessing for tobacco addiction alongside other substance addictions. Although
      smoking did not decrease according to the Nic-BAM, an increase in the use of
      nicotine-replacement products suggests that participants are willing to initiate
      a quit attempt during SUD treatment. The availability of new evidence-based
      approaches for integration of tobacco cessation with mental health and SUD
      treatment may help to enhance programmatic efforts. Environmental changes are
      needed to fully incorporate tobacco recovery into SUD programming, and additional
      resources may include peer support specialists. 

PMID- 24094923
TI  - Prevalence of malignancy in patients with pure main duct intraductal papillary
      mucinous neoplasms.
AB  - BACKGROUND: Risk of malignancy in main duct intraductal papillary mucinous
      neoplasm (MD-IPMN) ranges from 36% to 100% in the literature. Although surgical
      resection is recommended for all MD-IPMNs, the risk of malignancy based on main
      pancreatic duct (MPD) size alone remains unclear. OBJECTIVE: To assess the
      prevalence of malignancy in symptomatic and asymptomatic patients with pure MD
      IPMN based on MPD size. DESIGN: Single-center retrospective study of
      prospectively collected data. SETTINGS: Tertiary referral center. PATIENTS AND
      INTERVENTIONS: Fifty-two patients with pure low-risk MD-IPMN. Clinical,
      endoscopic, radiographic, and pathologic data were reviewed. MAIN OUTCOME
      MEASUREMENTS: Prevalence of malignancy in patients with pure MD-IPMN based on
      histopathology of resected lesions. RESULTS: Sixteen asymptomatic patients had
      pure MD-IPMN on surgical pathology, 4 (25%) with malignant disease, compared with
      25 of 36 symptomatic patients (69%) with pure MD-IPMN. Logistic regression
      identified symptoms and MPD size as predictors of malignancy. Receiver operating
      characteristic curve analysis demonstrated that MPD size (optimal cutoff of 8 mm)
      produced the greatest area under the curve to discriminate between benign and
      malignant MD-IPMN (.83; 95% CI, .72-.94). MPD size greater than 8 mm has a
      relative risk of 2.8 for malignancy (95% CI, 1.6-4.9). LIMITATIONS:
      Retrospective, single-center study at a tertiary referral hospital. Study
      population included only patients who underwent surgical resection. CONCLUSION:
      Asymptomatic MD-IPMN patients with a duct size of no more than 8 mm have a lower
      prevalence of malignancy and may represent a distinct group of patients with less
      aggressive biologic behavior. Further studies are needed to confirm our
      observations.

PMID- 24094922
TI  - Drinking motives as moderators of the effect of ambivalence on drinking and
      alcohol-related problems.
AB  - The current study seeks to evaluate relationships between drinking motives and
      alcohol-related ambivalence in the prediction of problem drinking. We expected
      that: 1) main effects would emerge such that alcohol-related ambivalence would be
      positively associated with peak drinking and problems; drinking motives would be
      positively associated with drinking and problems, and 2) interactions would
      emerge between motives and ambivalence in predicting problematic drinking such
      that drinking motives would be positively associated with peak drinking and
      problems, especially among those high in ambivalence over drinking. Six hundred
      sixty-nine undergraduate students (mean age=22.95, SD=5.47, 82.22% female)
      completed study materials. Results showed that consistent with expectations,
      ambivalence was positively associated with peak drinking and problems. Further,
      consistent with expectations, drinking motives were positively associated with
      peak drinking and problems. Additionally, ambivalence was positively associated
      with drinking motives. Significant interactions emerged between drinking motives
      (social and coping) and ambivalence when predicting peak drinking and alcohol
      related problems. These findings highlight the importance of considering motives
      in the relationship between ambivalence and drinking. Clinical implications
      include the need for tailoring interventions to target individual difference
      factors that increase risk for heavy drinking and associated problems. This is
      especially important among college students who may be at risk for problematic
      behavior. 

PMID- 24094924
TI  - [Emphysematous pancreatitis].

PMID- 24094925
TI  - Is lung surgery a good option for octogenarians?
AB  - INTRODUCTION: The number of geriatric patients with lung cancer is expected to
      increase in the next few years, especially patients over 80, and therefore it is
      important to know where the therapeutic limits should be drawn. Is surgery a good
      option in patients over 80? OBJECTIVE: To show the results of lung resection in
      patients over 80 years of age to evaluate the safety and short-term results.
      MATERIAL AND METHODS: Retrospective study of 21 patients who underwent lung
      resection between October 1999 and October 2011. RESULTS: The mean age of the
      patients was 82 +/- 2; 13 lobectomies were performed,5 transegmental resections,
      2 segmentectomies, and 1 pneumonectomy. Postoperative complications (28.6%) were:
      respiratory 66.6%, cardiological 16.7% and digestive 16,7%. Perioperative
      mortality was 9,5% (2). There was a significant association between mortality and
      age (P=.023), or pneumonectomy (P=.002). We studied COPD as a risk factor for
      mortality and found a statistically significant relation with the need for ICU
      (P<.007), and the appearance of complications (P<.044). CONCLUSIONS: Resective
      lung surgery is feasible and safe in selected patients over 80 years of age. In
      our experience, squamous cell carcinoma was the most frequent tumor. The most
      common procedure was lobectomy which is a safe technique with a low complication
      rate in elderly patients. Pneumonectomy should be avoided, as we have found a
      significant association with perioperative mortality.

PMID- 24094926
TI  - Laparoscopic first stage in a two-stage hepatectomy.

PMID- 24094927
TI  - [Enterocele containing cecum and terminal ileum at labium majus level].

PMID- 24094928
TI  - Cystic duct remnant syndrome: myth or reality?

PMID- 24094929
TI  - [Mycotic aneurysm of the abdominal aorta caused by Campylobacter fetus].

PMID- 24094930
TI  - Surgical resection of a functional paraganglioma diagnosed by mediastinoscopy.

PMID- 24094931
TI  - Proteostasis and aging of stem cells.
AB  - The accumulation of misfolded or damaged proteins is an important determinant of
      the aging process. Mechanisms that promote the homeostasis of the proteome, or
      proteostasis, can slow aging and decrease the incidence of age-related diseases.
      Adult stem cell function declines during the aging process of an organism. This
      demise of somatic stem cell function could contribute to tissue degeneration and
      organismal aging. Accumulation of damaged proteins in embryonic stem cells (ESCs)
      may also have an impact on the aging process, because the passage of these
      proteins to progenitor cells during asymmetric division could compromise
      development and aging. Therefore, proteostasis maintenance in stem cells might
      have an important role in organismal aging. In this review, we discuss exciting
      new insights into stem cell aging and proteostasis and the questions raised by
      these findings. 

PMID- 24094934
TI  - When less is more: a simple predictive model for repeated prostate biopsy
      outcomes.
AB  - OBJECTIVES: To present a new predictive model for repeated prostate biopsy
      outcomes. Several practical problems are described that arise when searching for
      a proper model among those that already exist. A new model is developed with only
      two explanatory variables and a simple graphical output. METHODS: This is a
      retrospective cohort study based on data collected from December 2006 to June
      2011 at the Clinic of Urology of the University Hospital in Olomouc, Czech
      Republic. The cohort consists of 221 patients who underwent the first repeated
      biopsy after an initial biopsy with a negative outcome. All patients had prostate
      specific antigen (PSA) levels between 1.5 and 16.5 ng/mL and a prostate volume
      not greater than 100mL. A logistic regression model was fitted. RESULTS: Of the
      221 patients, 29 (13%) were diagnosed with prostate cancer on the repeated
      biopsy. The final model includes the PSA level and the transitory zone volume as
      predictors. Its accuracy is 76.4%. The cut-off point of 0.0687 in the predicted
      positive repeated biopsy outcome assures 95% sensitivity and prevents 42% of
      unnecessary biopsies. CONCLUSIONS: The accuracy of the model is comparable to
      that of more complex models (with more than two predictors) published in the
      literature. The model includes only two routinely measured variables, and hence
      it is accessible for a wide range of practitioners. The simple graphical outcome
      makes the model even more attractive.

PMID- 24094932
TI  - 53BP1: pro choice in DNA repair.
AB  - The DNA damage response factor 53BP1 functions at the intersection of two major
      double strand break (DSB) repair pathways--promoting nonhomologous end-joining
      (NHEJ) and inhibiting homology-directed repair (HDR)--and integrates cellular
      inputs to ensure their timely execution in the proper cellular contexts. Recent
      work has revealed that 53BP1 controls 5' end resection at DNA ends, mediates
      synapsis of DNA ends, promotes the mobility of damaged chromatin, improves DSB
      repair in heterochromatic regions, and contributes to lethal mis-repair of DSBs
      in BRCA1-deficient cells. Here we review these aspects of 53BP1 and discuss new
      data revealing how 53BP1 is loaded onto chromatin and uses its interacting
      factors Rif1 and PTIP to promote NHEJ and inhibit HDR.

PMID- 24094933
TI  - Cognitive decline in short and long sleepers: a prospective population-based
      study (NEDICES).
AB  - BACKGROUND: It is not clear whether cognitive decline progresses more quickly in
      long sleepers than in short sleepers or than in participants with usual sleep
      duration. We assessed cognitive decline as a function of self-reported sleep
      duration in a prospective population-based cohort (NEDICES). METHODS:
      Participants were evaluated at baseline and 3 years later. Baseline demographic
      variables were recorded and participants indicated their daily sleep usual
      duration as the sum of nighttime sleep and daytime napping. The average daily
      total usual sleep duration was grouped into three categories: <= 5 h (short
      sleepers), 6-8 h (reference category), and >= 9 h (long sleepers). At baseline
      and at follow-up, a 37-item version of the Mini-Mental State Examination (37
      MMSE) was administered. RESULTS: The final sample, 2715 participants (72.9 +/-
      6.1 years), comprised 298 (11%) short sleepers, 1086 (40%) long sleepers, and
      1331 (49%) in the reference group (6-8 h). During the three year follow-up
      period, the 37-MMSE declined by 0.5 +/- 4.0 points in short sleepers, 0.6 +/- 4.3
      points in long sleepers, and 0.2 +/- 3.8 points in the reference group (p =
      0.08). The difference between short sleepers and the reference group was not
      significant (p = 0.142); however, the difference between long sleepers and the
      reference group was significant (p = 0.040). In analyses adjusted for baseline
      age and other potential confounders, this difference remained robust.
      CONCLUSIONS: In this study, cognitive test scores among long sleepers declined
      more rapidly than observed in a reference group. Additional studies are needed to
      confirm these results.

PMID- 24094935
TI  - In vivo performance of a drug-eluting contact lens to treat glaucoma for a month.
AB  - For nearly half a century, contact lenses have been proposed as a means of ocular
      drug delivery, but achieving controlled drug release has been a significant
      challenge. We have developed a drug-eluting contact lens designed for prolonged
      delivery of latanoprost for the treatment of glaucoma, the leading cause of
      irreversible blindness worldwide. Latanoprost-eluting contact lenses were created
      by encapsulating latanoprost-poly(lactic-co-glycolic acid) films in methafilcon
      by ultraviolet light polymerization. In vitro and in vivo studies showed an early
      burst of drug release followed by sustained release for one month. Contact lenses
      containing thicker drug-polymer films demonstrated released a greater amount of
      drug after the initial burst. In vivo, single contact lenses were able to
      achieve, for at least one month, latanoprost concentrations in the aqueous humor
      that were comparable to those achieved with topical latanoprost solution, the
      current first-line treatment for glaucoma. The lenses appeared safe in cell
      culture and animal studies. This contact lens design can potentially be used as a
      treatment for glaucoma and as a platform for other ocular drug delivery
      applications.

PMID- 24094936
TI  - The role of elevated autophagy on the synaptic plasticity impairment caused by
      CdSe/ZnS quantum dots.
AB  - It is well known that autophagy, a cellular stress response to degrade damaged
      components, can be activated by many nanoparticles. We have demonstrated that
      CdSe/ZnS quantum dots (QDs), which are widely applied in vitro for diagnostics
      and cellular imaging, can impair synaptic transmission and synaptic plasticity in
      the dentate gyrus (DG) area, but the mechanism is still unclear. Here we show
      that elevated autophagy is at least partly responsible for this synaptic
      dysfunction induced by QDs in vivo. QDs elicited autophagy in the HeLa cells and
      cultured hippocampal neurons as well, accompanied with GFP-light chain protein 3
      (LC3) puncta dots and autophagosome formation, extensive conversion of LC3-I to
      LC3-II and a significant decrease of p62. Furthermore, we found that autophagy
      inhibitors (wortmannin, 3-MA or chloroquine) suppressed QDs-induced autophagic
      flux, partly blocked LTP impairment, coincident with down-regulation of synapsin
      I and synapse deficits by QDs in the hippocampal CA1 area. Our studies have
      important implications in providing a potential clinical remedy for brain damage
      caused by nanomaterials and in designing safer nanoparticles.

PMID- 24094937
TI  - A systematic in-vivo toxicity evaluation of nanophosphor particles via zebrafish
      models.
AB  - Lanthanide ion-doped nanophosphors are an emerging group of nanomaterials with
      excellent optical properties, and have been suggested as alternatives to quantum
      dots. In this letter, we determine the in-vitro and in-vivo toxicity of beta
      NaYF4:Ce,Tb nanophosphors using Capan-1 cells and embryonic zebrafish,
      respectively. In particular, we are the first to report on the in-vivo toxicity
      of beta-phase nanophosphors and examine phenotypic developmental abnormalities
      (growth retardation, heart deformity, and bent tail), apoptotic cell death, and
      changes in heart function due to the nanophosphors. This study suggests the use
      of beta-NaYF4:Ce,Tb nanophosphors as alternatives for QDs in a wide variety of
      biomedical imaging applications. 

PMID- 24094938
TI  - Directing GPCR-transfected cells and neuronal projections with nano-scale
      resolution.
AB  - Surface modification technology has made significant advances in recent years
      towards the miniaturization and organization of traditional cell culture systems.
      However, the capability of directing transfected cells and neuronal connections
      to probe small structures such as spines is still under development. In the
      current work, interactions of different micropatterned substrates with HEK 293,
      CF10 cell lines, and primary neuronal cultures are evaluated. Using conventional
      and confocal fluorescence microscopies, several morphological and behavioral
      aspects of all three cell types were investigated. The immortalized cell lines
      were able to attach to the substrate and interact with neighboring cells.
      Similarly, cortical neurons formed connections guided by the micropatterns.
      Transfection of HEK 293 or CF10 cell lines with specific members of the G protein
      coupled receptor family did not alter the behavior of these cells in the
      micropatterns. On the other hand, neuronal projections were efficiently isolated
      by the patterns, simplifying the localization of spines with nano-scale
      resolution probed by atomic force microscopy. This work presents a valuable
      approach to isolate cells or to constrain important cell structures to grow along
      a desired pattern, thus facilitating advanced biological studies. 

PMID- 24094939
TI  - PHACOS, a functionalized bacterial polyester with bactericidal activity against
      methicillin-resistant Staphylococcus aureus.
AB  - Biomaterial-associated infections represent a significant clinical problem, and
      treatment of these microbial infections is becoming troublesome due to the
      increasing number of antibiotic-resistant strains. Here, we report a naturally
      functionalized bacterial polyhydroxyalkanoate (PHACOS) with antibacterial
      properties. We demonstrate that PHACOS selectively and efficiently inhibits the
      growth of methicillin-resistant Staphylococcus aureus (MRSA) both in vitro and in
      vivo. This ability has been ascribed to the functionalized side chains containing
      thioester groups. Significantly less (3.2-fold) biofilm formation of S. aureus
      was detected on PHACOS compared to biofilms formed on control poly(3
      hydroxyoctanoate-co-hydroxyhexanoate) and poly(ethylene terephthalate), but no
      differences were observed in bacterial adhesion among these polymers. PHACOS
      elicited minimal cytotoxic and inflammatory effects on murine macrophages and
      supported normal fibroblast adhesion. In vivo fluorescence imaging demonstrated
      minimal inflammation and excellent antibacterial activity for PHACOS compared to
      controls in an in vivo model of implant-associated infection. Additionally,
      reductions in neutrophils and macrophages in the vicinity of sterile PHACOS
      compared to sterile PHO implant were observed by immunohistochemistry. Moreover,
      a similar percentage of inflammatory cells was found in the tissue surrounding
      sterile PHACOS and S. aureus pre-colonized PHACOS implants, and these levels were
      significantly lower than S. aureus pre-colonized control polymers. These findings
      support a contact active surface mode of antibacterial action for PHACOS and
      establish this functionalized polyhydroxyalkanoate as an infection-resistant
      biomaterial.

PMID- 24094940
TI  - Part one: for the motion. young patients with good risk factors should be treated
      with EVAR.

PMID- 24094941
TI  - Response to 're. doppler ultrasound examination of multiple sclerosis patients
      and control participants: inter-observer agreement and association with disease'.

PMID- 24094942
TI  - Re. 'doppler ultrasound examination of multiple sclerosis patients and control
      participants: inter-observer agreement and association with disease'.

PMID- 24094943
TI  - Biomass fuel use and the risk of asthma in Nigerian children.
AB  - BACKGROUND: Biomass fuel smoke exposure contributes to respiratory infections in
      childhood, but its association with asthma has not been established. We studied
      the relationship of biomass fuel use with asthma symptoms and lung function in
      Nigerian children. METHODS: A cross-sectional study was performed in 299 village
      children aged 5-11 years in North Central Nigeria. Data were collected regarding
      the cooking fuels used and duration of daily smoke exposure in the cooking area.
      Asthma symptoms were assessed with a modified International Study of Asthma and
      Allergies in Childhood (ISAAC) questionnaire, and lung function was assessed with
      spirometry. RESULTS: The prevalence of a lifetime history of wheeze was 9.4% (95%
      CI: 6.3%-13.2%). Fourteen children (4.7%) had airway obstruction (FEV1/FEV6
      <85%). Female subjects had lower FEV1 and FEV6 (110 % and 120% percent predicted,
      respectively) than males (121% and 130%, respectively, P <0.001 for both
      differences). Advancing age was associated with a relative decline in the
      predicted value of FEV1 of 7.8 % per year (r = -0.61; P < 0.001). Children in
      families that used firewood daily did not have a significantly increased
      likelihood of asthma-related symptoms (OR = 2.36, 95% CI: 0.66-8.44). Similarly,
      airway obstruction did not differ significantly between children in households
      that did and did not use firewood daily (mean FEV1/FEV6 of 0.95 and 0.97,
      respectively; P = 0.41). CONCLUSION: Reported smoke exposure was not associated
      with an increased risk of asthma symptoms or airway obstruction. However,
      lifetime smoke exposure may explain the reduction in spirometric values in female
      subjects and with advancing age.

PMID- 24094944
TI  - Measuring habitual physical activity in adults with cystic fibrosis.
AB  - BACKGROUND: The aim of the present study was to determine whether different
      methods of recording physical activity (PA), i.e., accelerometers vs
      questionnaires, provided similar information in adults with cystic fibrosis (CF).
      METHODS: 20 CF (age 33 +/- 8SD yrs, FEV1 68 +/- 16% predicted) and 11 age-matched
      healthy controls completed the Habitual Activity Estimation Scale (HAES)
      questionnaire and wore a biaxial accelerometer (SenseWear Pro3 Armband). Exercise
      tolerance was measured in CF. RESULTS: Patients had similar values in PA compared
      with controls. None of PA categories estimated by HAES questionnaire correlated
      with PA categories measured by the accelerometer; in CF the HAES questionnaire
      overestimated the effective levels of PA measured by the accelerometer. There
      were no differences between weekdays and weekend days PA levels provided by the
      accelerometer. In CF the questionnaire detected different time reported during
      the "somewhat inactive" and "somewhat active" categories (z = 2.651; p = 0.008; z
      = -2.651; p = 0.008), weekdays vs weekend; patients reported more time spent in
      activity (somewhat active & very active) during the weekend (z = -2.203; p =
      0.02). Peak oxygen uptake correlated with accelerometer activities of "moderate"
      (>4.8 metabolic equivalents (METS)) and "vigorous" (>7.2 METS) intensity (r =
      0.503, p = 0.02; r = 0.545, p = 0.01). CONCLUSIONS: In adults with cystic
      fibrosis PA levels are better evaluated by the accelerometer and are similar to
      the controls. PA measured by the accelerometer is similar during the week and
      correlates with exercise tolerance.

PMID- 24094945
TI  - Management of sickle cell disease from childhood through adulthood.
AB  - Sickle cell disease (SCD) is a genetic disorder characterised by anaemia and
      "sickling" of red blood cells, leading to chronic haemolytic anaemia, vascular
      injury, and organ dysfunction. Although children and adults experience many
      similar symptoms and problems, complications increase with age, leading to early
      mortality. Hydroxyurea (hydroxycarbamide), the only US Food and Drug
      Administration-approved treatment, continues to be under-utilised and other
      treatments available to children are often inaccessible for adults.
      Haematopoietic stem-cell transplantation is a curative option, but is limited by
      a lack of donors and concerns for transplant-related toxicities. Although
      comprehensive programs exist in paediatrics, affected adults may not have access
      to preventative and comprehensive healthcare because of a lack of providers or
      care coordination. They are often forced to rely on urgent care, leading to
      increased healthcare utilisation costs and inappropriate treatment. This problem
      highlights the importance of primary care during the transition from paediatrics
      to adulthood. 

PMID- 24094946
TI  - Primary cutaneous neuroendocrine carcinoma, Merkel cell carcinoma. Case series
      1991-2012.
AB  - INTRODUCTION AND OBJECTIVES: Merkel cell carcinoma was first described by Toker
      in 1972. It is an uncommon, primary neuroendocrine skin carcinoma which appears
      in the dermoepidermic area, grows fast, is very aggressive and has a poor
      prognosis. The aim of this work is to highlight the importance of this tumour,
      which develops mainly in the skin of the head and neck area, and whose prevalence
      has increased in recent years. MATERIAL AND METHOD: We gathered data on 16
      patients suffering cutaneous neuroendocrine carcinoma treated at our hospital
      between September 12, 1991 and July 13, 2012. We indicated the age and gender of
      patients. We described the area where the tumour was located, indicating the size
      in millimetres, according to the major axis of the lesion. RESULTS: Most of the
      patients studied were over 70 years old, except for one who was 55. The highest
      frequency of cases appeared among patients aged over 80 years. In the cases
      studied, when the tumour appeared in the head and neck region (10/16), its
      location could be nasal-lateronasal, cheek-malar, upper eyelid, frontal or
      mandibular. The major axis of the lesion ranged between 7 and 35 mm. Unlike with
      epidermoid or basocellular carcinomas, recurrence and ganglionar metastases were
      common. Immunohistochemical (CK20) tests are essential for a correct diagnosis.
      Treatment is usually surgical and occasionally followed by radiotherapy and
      chemotherapy. CONCLUSION: This carcinoma is not a very common skin tumour. It
      appears in old age, in the head and neck region in 50% of cases and often leads
      to exitus.

PMID- 24094948
TI  - Perinatal management of congenital oropharyngeal tumors: the ex utero intrapartum
      treatment (EXIT) approach.
AB  - PURPOSE: To present our experience in the perinatal management of fetuses with
      large oropharyngeal tumors by ex utero intrapartum treatment (EXIT). METHODS: We
      performed a retrospective chart review of all patients with congenital
      oropharyngeal tumor who underwent an EXIT procedure between May 2006 and June
      2012. RESULTS: Four patients were included in the series, three females and one
      male. The diagnoses were epignathus (n=2) and congenital epulis (n=2). Three
      EXITs were done at term and one at late preterm due to premature rupture of
      membranes. Median maternal time under anesthesia was 185 min (range: 166-281) and
      median maternal operative time was 99 min (range: 85-153). Median maternal blood
      loss was 550 ml (range: 350-2000); one mother required a blood transfusion. Mean
      maternal hospital stay was 4 days. Median hysterotomy-to-cord clamp time was 24
      min (range: 18-66). Mean fetal birth weight was 2.7 kg (range: 2.4-3). The airway
      was successfully accessed and secured under placental circulation in all cases.
      In the two patients with congenital epulis the tumors were resected at the base
      of their pedicles and the airway accessed via direct laryngoscopy before the
      umbilical cord was clamped. One patient with epignathus underwent a retrograde
      tracheal intubation under placental circulation and had the tumor resected
      thereafter. The second patient with epignathus had a tracheostomy done under
      placental circulation and then had tumor debulking immediately after the EXIT.
      The maternal morbidity was minimal and there were no mortalities. CONCLUSIONS: We
      conclude that the EXIT procedure is the ideal delivery strategy for fetuses with
      prenatally diagnosed oropharyngeal tumors and potential airway obstruction at
      birth. Patients with prenatally diagnosed oropharyngeal tumors should be promptly
      referred to a fetal treatment center with a dedicated multidisciplinary team and
      EXIT capabilities.

PMID- 24094947
TI  - Developmental outcomes of children with congenital diaphragmatic hernia: a
      multicenter prospective study.
AB  - PURPOSE: To determine developmental outcomes and associated factors in patients
      with congenital diaphragmatic hernia (CDH) at 2 years of age. METHODS: This is a
      multicenter prospective study of a CDH birth cohort. Clinical and socioeconomic
      data were collected. Bayley Scales of Infant Development (BSID-III) and Vineland
      Adaptive Behavior Scales (VABS-II) were performed at 2 years of age. RESULTS:
      BSID-III and VABS-II assessments were completed on 48 and 49 children,
      respectively. The BSID-III mean cognitive, language, and motor scores were
      significantly below the norm mean with average scores of 93 +/- 15, 95 +/- 16,
      and 95 +/- 11. Ten percent (5/47) scored more than 2 standard deviations below
      the norm on one or more domains. VABS-II scores were similar to BSID-III scores
      with mean communication, daily living skills, social, motor, adaptive behavior
      scores of 97 +/- 14, 94 +/- 16, 93 +/- 13, 97 +/- 10, and 94 +/- 14. For the BSID
      III, supplemental oxygen at 28 days, a prenatal diagnosis, need for
      extracorporeal membrane oxygenation (ECMO) and exclusive tube feeds at time of
      discharge were associated with lower scores. At 2 years of age, history of
      hospital readmission and need for tube feeds were associated with lower scores.
      Lower socioeconomic status correlated with lower developmental scores when
      adjusted for significant health factors. CONCLUSION: CDH patients on average have
      lower developmental scores at 2 years of age compared to the norm. A need for
      ECMO, oxygen at 28 days of life, ongoing health issues and lower socioeconomic
      status are factors associated with developmental delays.

PMID- 24094949
TI  - Changes in chest compression indexes with breathing underestimate surgical
      candidacy in patients with pectus excavatum: a computed tomography pilot study.
AB  - BACKGROUND: Haller Index (HI) >=3.25 by computed tomography (CT) at end
      inspiration has been used to indicate surgical correction in patients with pectus
      excavatum. However, chest wall diameters vary with breathing and may modify HI
      values and surgical indications. The aim of our study was to report the changes
      in HI with breathing and their impact in the surgical indication rates. METHODS:
      Thirty six patients with pectus excavatum underwent chest CT evaluation at both
      end-inspiration and end-expiration. HI was derived by dividing the transverse
      diameter (TD) of the chest by the anteroposterior diameter (APD). Cardiac
      compression index (CCI) was then calculated by dividing the cardiac TD by the
      APD. RESULTS: Mean patient age was 19 +/- 7 years old and 86.8% were males. From
      end-inspiration to end-expiration, large changes in APD values corresponded to
      large changes (29.6%) in HI values. CCI increased significantly during end
      expiration, primarily driven by an increase on the cardiac TD. Surgical
      indication was found in 71% and 91% of patients during end-inspiration and end
      expiration, respectively (p<0.05). CONCLUSIONS: This study showed that the
      severity indexes of the pectus excavatum were all significantly more severe at
      end-expiration than at end-inspiration, leading to an increase in surgical
      candidacy. We therefore recommend performing the CT at end-expiration.

PMID- 24094950
TI  - Validation of the pediatric surgical risk assessment scoring system.
AB  - BACKGROUND: Within the adult population, there exist numerous validated risk
      stratification tools aimed at predicting postoperative outcomes using
      preoperative and intraoperative parameters. However, similar tools for the
      pediatric population are scarce. We previously developed and reported on a
      scoring system to predict postoperative complications in children undergoing
      surgery at Boston Children's Hospital. The objective of this study was to
      validate our scoring system to determine its effectiveness in identifying
      children at risk for major complications or death within 30 days following
      surgery. STUDY DESIGN: A computer program randomly selected 2015 out of 11,734
      patients who underwent surgery at our institution in 2009. The severity of the
      complications was graded based on the Clavien classification system, with major
      complications being a grade III or higher. The Preoperative Complication Score
      (PCS) and the Overall Complication Score (OCS) were calculated for all patients,
      and Receiver Operating Characteristic (ROC) curves were generated for each
      scoring system. RESULTS: The overall incidence of major complications was 3.9%
      (79 patients). Proportionally, cardiac surgery had the highest percentage of
      major complications (20% of the performed surgeries). Both PCS and OCS
      demonstrated excellent correlation with postoperative outcomes with c-statistic
      values of 0.740 (CI 0.682-0.800, p < 0.001) and 0.767 (CI 0.712-0.822, p < 0.001)
      respectively. CONCLUSIONS: We determined that both the PCS and OCS are effective
      in identifying children at risk for major complications and death following
      surgery. Further studies will be needed to determine if these scoring systems are
      applicable to children undergoing surgery at other institutions and if the use of
      the scoring systems would result in improved clinical outcomes and reduced costs.

PMID- 24094951
TI  - Outcomes of early versus late intestinal operations in patients with
      gastroschisis and intestinal atresia: results from a prospective national
      database.
AB  - BACKGROUND: Gastroschisis may be complicated by intestinal atresia, necrosis,
      and/or perforation. In the absence of an urgent indication, intestinal procedures
      are often delayed to allow for bowel recovery. This practice has not been
      evaluated. METHODS: We queried a prospective Canadian database of all patients
      with gastroschisis born between 2005 and 2011. Patients with intestinal atresia
      who underwent an intestinal operation during the first 21 days of life (EARLY
      GROUP) were compared with those who underwent operations later (LATE GROUP).
      RESULTS: Of 629 gastroschisis patients, 78 (12.4%) had intestinal complications;
      27 patients (4.3%) had intestinal operations for atresia without necrosis or
      perforation - 14 EARLY and 13 LATE. Baseline clinical parameters were similar
      between the two groups. There was a decreased incidence of the following
      complications in the EARLY group but none reached statistical significance: post
      operative bowel obstruction (28.6% vs. 61.5%, p = 0.1); line sepsis (14.3% vs.
      30.8 %, p = 0.4); and wound infection (14.3% vs. 46.1%, p = 0.1). Earlier
      tolerance of enteral feeding in the EARLY group was manifested by younger age at
      first enteral feeding (14.8 + 2.6 vs. 44.7 + 7.4 days, p = 0.002) and higher
      tolerance of enteral feeding at 28 days of life [less patients exclusively on TPN
      (28.6% vs. 61.5%, p = 0.06), and more patients on more than 50 cc kg(-1)day(-1)
      of enteral feeding (42.9% vs. 7.7%, p = 0.08)]. CONCLUSIONS: Early intestinal
      operations in patients with gastroschisis and intestinal atresia are not
      associated with increased complications, and allow patients to receive and
      tolerate enteral feeding earlier.

PMID- 24094952
TI  - Early results of an objective feedback-directed system for the staged traction
      repair of long-gap esophageal atresia.
AB  - PURPOSE: Treatment of long-gap esophageal atresia challenges pediatric surgeons.
      Dr. Foker described utilization of external traction sutures to promote in-vivo
      growth through tension-induced lengthening, but reproducibility of this technique
      is difficult. We describe a safe and reproducible traction system using
      transduction of hydrostatic pressure as a surrogate for tension. METHODS: We
      conducted a multi-institutional review of patients treated with this system from
      2005 to 2012. All children had sutures applied to both pouches with continuous
      measurement of associated hydrostatic pressures (tension). Main outcome measures
      were days to delayed primary repair and thoracotomies prior to primary repair.
      RESULTS: Seven children were included. Median time to delayed repair was 15 days
      (range: 6-47 days). Three patients required repeat thoracotomies owing to
      mechanical entrapment of a pouch, all identified early by this system. All
      required postoperative dilations. Three had self-limited postdilation leaks, and
      there was one operation-related leak. CONCLUSIONS: This system provides
      reproducible traction application, facilitating staged primary repair by
      preventing major failures through limiting excessive traction and guides re
      exploration for trapped segments. Larger studies are needed to determine the
      optimal tension protocol, prevent postoperative leaks, while decreasing the need
      for dilations and time to enteral feeding.

PMID- 24094953
TI  - Intramural injection with botulinum toxin significantly elongates the pig
      esophagus.
AB  - BACKGROUND/PURPOSE: Surgical treatment of long-gap esophageal atresia (LGEA) is
      challenging. Methods which facilitate stretching of the esophageal pouches may
      allow primary anastomosis. Botulinum toxin type A (BTX-A) blocks acetylcholine
      release in neuromuscular junctions, thereby causing muscle relaxation. We
      hypothesized that intramural injections with BTX-A into the esophageal wall of
      piglets would significantly elongate the tissue upon stretch. METHODS: Twenty
      four piglets were randomized to receive BTX-A of placebo (saline). After one
      hour, the esophagus was removed en bloc and tested in a stretch-tension device.
      RESULTS: The mean esophageal elongation was 84% (range 83-101) in the BTX-A-group
      and 65% (50-78) in the control group. The mean difference between the two groups
      was 18%, which was significant (p < 0.001). CONCLUSION: Intramural injections
      with botulinum toxin type A elongate the esophagus significantly. Clinically,
      this could be a potential method to achieve primary anastomosis in LGEA.
      Additional clinical studies are necessary to evaluate the method before it can be
      generally recommended.

PMID- 24094954
TI  - Novel exomphalos genetic mouse model: the importance of accurate phenotypic
      classification.
AB  - BACKGROUND: Rodent models of abdominal wall defects (AWD) may provide insight
      into the pathophysiology of these conditions including gut dysfunction in
      gastroschisis, or pulmonary hypoplasia in exomphalos. Previously, a Scribble
      mutant mouse model (circletail) was reported to exhibit gastroschisis. We further
      characterise this AWD in Scribble knockout mice. METHOD: Homozygous Scrib
      knockout mice were obtained from heterozygote matings. Fetuses were collected at
      E17.5-18.5 with intact amniotic membranes. Three mutants and two control fetuses
      were imaged by in amnio micro-MRI. Remaining fetuses were dissected, photographed
      and gut length/weight measured. Ileal specimens were stained for interstitial
      cells of Cajal (ICC), imaged using confocal microscopy and ICC quantified.
      RESULTS: 127 fetuses were collected, 15 (12%) exhibited AWD. Microdissection
      revealed 3 mutants had characteristic exomphalos phenotype with membrane-covered
      gut/liver herniation into the umbilical cord. A further 12 exhibited extensive
      AWD, with eviscerated abdominal organs and thin covering membrane (intact or
      ruptured). Micro-MRI confirmed these phenotypes. Gut was shorter and heavier in
      AWD group compared to controls but morphology/number of ICC was not different.
      DISCUSSION: The Scribble knockout fetus exhibits exomphalos (intact and
      ruptured), in contrast to the original published phenotype of gastroschisis.
      Detailed dissection of fetuses is essential ensuring accurate phenotyping and
      result reporting.

PMID- 24094955
TI  - Fate of the uterus in 46XX cloacal exstrophy patients.
AB  - PURPOSE: Genetically female cloacal exstrophy (46XX CE) patients develop
      complications later in life due to their abnormal uterine anatomy, resulting in
      various invasive gynecologic procedures. Furthermore, they have difficulty
      becoming pregnant, and if they do conceive, they are unlikely to carry the
      pregnancy to term. We performed this review to determine the rate of
      gynecological complications, the fate of the uterus, and the rate of pregnancy in
      46XX cloacal exstrophy patients. METHODS: All charts for 46XX CE patients treated
      by us were reviewed following IRB approval. Patient age at last follow-up,
      surgical management of the uterus, uterine complications, and pregnancies were
      recorded. RESULTS: The charts of all 16 of our 46XX CE patients who survived past
      the neonatal period were reviewed. Two patients underwent hemi-hysterectomy (HH):
      1 for an atretic hemi-uterus at birth, another for abnormal uterine insertion at
      3 years. A third patient initially had HH for hydrometrocolpos leading to
      ureteral and colonic obstruction at 14 years but she required a completion
      hysterectomy a year later. Four patients underwent total hysterectomy (TH) at the
      outset: 2 neonates for a diminutive uterus with extreme disparity in the halves,
      another for uterine prolapse at 1 month of age, and a fourth for
      hematometrocolpos at 16 years of age. Six patients reached adulthood without
      requiring gynecologic intervention; one of these six is now being managed at
      another institution. Two patients are prepubertal and one was lost to follow-up.
      The only patient in the series who became pregnant miscarried at 11 weeks
      gestation. CONCLUSION: Out of 13 post-pubertal patients 6 have retained the
      entire uterus and another 2 had a hemi-hysterectomy. One patient who became
      pregnant miscarried at 11 weeks gestation. We believe it is appropriate to avoid
      ablative genital surgery as far as possible and for these patients to become
      pregnant after detailed discussion with physicians experienced in the care of
      46XX CE patients.

PMID- 24094956
TI  - Dysregulation of upstream and downstream transforming growth factor-beta
      transcripts in livers of children with biliary atresia and fibrogenic gene
      signatures.
AB  - INTRODUCTION: Our previous work demonstrated that the transforming-growth factor
      (TGF) beta pathway plays a central role in the liver fibrosis associated with
      experimental biliary atresia (BA). To confirm these findings in humans, we
      performed an in silico analysis of publicly available microarray data from liver
      specimens from children with BA, with the hypothesis that the TGF-beta pathway
      would be dysregulated. METHODS: We analyzed publicly available liver gene
      expression microarray data from 47 infants with BA. We re-analyzed the microarray
      image files and clinical data to compare gene expression differences between the
      fibrogenic and inflammatory cohorts identified in the initial study. Targets from
      the microarray analysis were confirmed using the animal model of BA. RESULTS:
      Analysis of variance (ANOVA) detected 6903 transcripts (2822 distinct genes)
      differentially regulated between groups (p < 0.01; fold change >1.2). We used a
      targeted approach to identified a subgroup of 24 TGF-beta-related transcripts.
      Expressions for procollagen transcripts were increased in the fibrogenic group
      (1.2-fold to 1.4-fold); expression of matrix metalloproteinase (MMP)-7 was
      similarly increased 2-fold, while MMP-9 and plasminogen activator inhibitor-1
      were decreased 2-fold and 3-fold respectively. Integrins beta5 (1.18-fold) and
      beta8 (1.84-fold) also demonstrated increased expression in the fibrogenic group.
      Increased expression of beta5 (3-fold) and beta8 (5-fold) as well as Smad-3 (4
      fold) and Smad interacting protein (SIP)-1 (3.5-fold) mRNA was confirmed in
      experimental BA. Phosphorylated Smad-3 protein in the experimental group was also
      nearly twice that of the control group, further implicating the TGF-beta pathway.
      CONCLUSION: Gene transcripts for known upstream and downstream TGF-beta mediators
      are differentially expressed in liver specimens from children with BA and a
      fibrogenic gene signature. The same integrins that were dysregulated in the human
      specimens were also found to be up-regulated in our animal BA model, as were
      other intermediaries in the TGF-beta pathway. Further investigation into whether
      these mediators may be attractive targets for future therapy in children with BA
      is warranted.

PMID- 24094957
TI  - Solid pseudopapillary neoplasm of the pancreas in children: a 15-year experience
      and the identification of a unique immunohistochemical marker.
AB  - PURPOSE: To review our 15-year experience in the management of children with
      solid pseudopapillary neoplasm (SPPN) of the pancreas at a single pediatric
      institution, to delineate a unique immunohistochemical marker for SPPN, and to
      analyze cumulative data on this rare entity in the literature. METHODS: We did a
      retrospective analysis of the demographic data, clinical presentation,
      immunohistochemical characteristics, surgical approach, and long-term outcomes of
      all patients diagnosed with SPPN between 1997 and 2012. RESULTS: There were 6
      patients in the series, 5 females and 1 male. Median age at presentation and at
      surgery was 15 years (11-18 years). Abdominal pain was the presenting symptom in
      5 cases and jaundice in 1 case. Two patients had a pancreatic head tumor and
      underwent a pylorus-preserving pancreaticoduodenectomy. Two patients had the
      tumor in the pancreatic tail and underwent a distal pancreatectomy with
      splenectomy. Two patients had the tumor in the pancreatic body and underwent a
      distal pancreatectomy with splenectomy in one case and with preservation of the
      spleen in the other. All tumors were completely resected with pathologic margins
      free of disease. The median maximum diameter was 6.8 cm (3 to 15 cm). On
      immunohistochemistry the tumors exhibited different combinations of non-specific
      markers like chromogranin, vimentin and neuron-specific enolase, but all tumors
      showed the highly SPPN-specific paranuclear dot-like immunoreactivity pattern for
      CD99 in the solid as well as in the pseudopapillary areas. No patient had
      metastasis at presentation. Median follow-up was 6.5 years (6 months to 15
      years). There were no recurrences, no long-term metastasis, and all patients are
      disease-free. CONCLUSION: Our series supports the concept that complete resection
      is necessary to achieve the best possible long-term results. Additionally, we
      demonstrate that SPPN exhibits a very unique immunostaining pattern for CD99 that
      is present in all cases.

PMID- 24094958
TI  - Surgical treatment of type IV-A choledochal cyst in a single institution:
      children vs. adults.
AB  - BACKGROUND: The treatment of type IV-A choledochal cyst is particularly difficult
      and remains a challenge because of the rareness and the various presentations of
      the disease involving not only the extrahepatic but also the intrahepatic biliary
      tract. The purpose of this study is to analyze our clinical experience for
      surgical treatment of type IV-A choledochal cyst, and compare between children
      and adults. METHODS: During a 10-year period of time (2000-2010), clinical data
      of 81 consecutive patients with type IV-A choledochal cyst were retrospectively
      analyzed. We divided these patients into two groups, the child group (age <= 18
      years) and the adult group (age >18 years). According to whether the patient
      received additional liver resection, patients were divided into a extrahepatic
      cystectomy (EHC) group and an additional liver resection (LR) group. The long
      term outcomes after surgery were evaluated in two groups. RESULTS: Of all 81
      patients, there were 17 children and 64 adults; 16 children and 35 adults
      belonged to EHC group, one child and 29 adults belonged to LR group. The
      morbidity of biliary stricture and/or lithiasis in the adults was significantly
      higher than that in the children (p = 0.041 < 0.05). In the EHC group, the
      reoperation rate of adults was significantly higher than that of children (p =
      0.019 < 0.05). For adult patients, the morbidity of biliary stricture and/or
      lithiasis and the reoperation rate in EHC group was significantly higher than
      that in LR group (p = 0.037 < 0.05 and p = 0.026 < 0.05 respectively). Five
      adults were found to have cholangiocarcinoma within a follow-up period, while no
      child was found to. However, for adult patients, no significant discrepancy was
      observed between EHC group and LR group (p = 0.366 > 0.05). CONCLUSIONS: The
      present study suggests that the children have better outcomes than adults for
      patients with type IV-A choledochal cyst after EHC, while LR brings better
      outcomes than EHC for adult patients.

PMID- 24094959
TI  - Ductus venosus closure results in transient portal hypertension--is this the
      silent trigger for necrotizing enterocolitis?
AB  - INTRODUCTION: The etiology of necrotizing enterocolitis (NEC) remains elusive and
      no definite trigger has been identified. There are no studies to date examining
      the potential role of closure of the ductus venosus (DV), its effect on
      increasing portal venous pressure (PVP) and its association to mesenteric venous
      ischemia in the development of NEC. Our aim was to develop an animal model to
      examine this physiology. METHODS: Fifteen near-term lambs were used. The DV was
      occluded in experimental animals by a balloon tip catheter, while the sham
      controls underwent catheterization without DV occlusion. Vital signs and PVP were
      monitored for 4h, followed by intestinal biopsy. RESULTS: The experimental group
      (n=5) demonstrated a significant increase in PVP following DV occlusion (11.87 mm
      Hg [95% CI: 11.40-12.34]), compared to controls (8.95 mm Hg [95% CI: 8.34-9.56])
      (F=12.16, p=0.001). Histology of the terminal ileum showed vacuolar degeneration,
      indicative of reversible cellular damage in the experimental group. CONCLUSIONS:
      We demonstrate that DV closure in the neonatal lamb leads to transient portal
      hypertension which is associated with cellular damage and inflammatory changes of
      the intestinal mucosa. Additional studies will be necessary to determine if the
      transient portal hypertension following DV closure leads to clinically apparent
      intestinal ischemia and NEC.

PMID- 24094960
TI  - The Pediatric Laparoscopic Surgery (PLS) simulator: methodology and results of
      further validation.
AB  - BACKGROUND: The Pediatric Laparoscopic Surgery (PLS) simulator is the only
      validated tool for pediatric Minimal Access Surgery. Construct validity (the
      ability to discriminate between novice, intermediate and expert) for the PLS
      simulator had previously been established on the basis of the total PLS score, as
      well as the individual performance on three of the five tasks. We describe the
      process and methods used to establish independent construct validity for a fourth
      task: pattern-cutting. METHODS: After considering various options for the
      possible modifications of the task itself, we retrospectively altered the way the
      pattern-cutting task was scored by modifying the weighting of precision versus
      time without changing the task itself. This was subsequently tested prospectively
      at the 2011 Canadian Association of Pediatric Surgeons meeting. RESULTS:
      Modification in the scoring metrics allowed differentiation within a previously
      tested cohort of 84 candidates (20 novices: score=48 +/- 16, 19 intermediates:
      score=59 +/- 18, 45 experts: score=69 +/- 12 p=0.01). This was validated
      prospectively in a cohort of 18 experts and 7 intermediates (65 +/- 8, 54 +/- 17
      p=0.03). CONCLUSIONS: Construct validity for the pattern-cutting task was
      established by modification of the scoring metrics. This was validated both
      retrospectively and prospectively.

PMID- 24094961
TI  - Heterotaxy syndrome and intestinal rotation abnormalities: a survey of
      institutional practice.
AB  - PURPOSE: Abnormalities of intestinal rotation (IRA) are commonly associated with
      heterotaxy syndrome (HS). There is controversy whether asymptomatic infants with
      HS require screening for IRA and if present, whether a prophylactic Ladd
      procedure is indicated. The objective of this study is to determine institutional
      practice across North America in the management of asymptomatic infants with HS
      and IRA. METHODS: We performed an international, multi-institutional web based
      survey to examine current practice and opinions in the management of IRA in HS
      patients. RESULTS: Overall response rate was 30%. Of physicians surveyed, 84%
      believe that HS patients should be screened for IRA in the neonatal period. 61%
      of general surgeons, 50% of cardiovascular surgeons and 45% of cardiologists feel
      that all patients with HS and an asymptomatic IRA should have a prophylactic Ladd
      procedure. 55% of physicians stated they would be comfortable with conservative
      management for patients with HS and asymptomatic IRA. CONCLUSIONS: The risk of
      midgut volvulus, morbidity and mortality from elective procedures and
      cardiovascular prognosis must be considered prior to an elective Ladd procedure
      on asymptomatic HS patients. There are practice variance among sub-specialists
      caring for these patients, a lack of expert consensus, and a paucity of evidence
      based data for IRA in this population.

PMID- 24094962
TI  - The clinical significance of pathological studies of congenital intestinal
      atresia.
AB  - OBJECTIVE: The purpose of this study was to explore the mechanisms of
      postoperative intestinal motility disorders in intestinal atresia patients by
      investigating the expression profiles of proteins, including calretinin (CR),
      glial-derived neurotrophic factor (GDNF), bone morphogenetic protein 2 (BMP-2), c
      kit, alpha-smooth muscle actin (alpha-SMA), and S-100 protein; to decipher the
      correlation between the area of the pathological segment and the alteration of
      the above 6 proteins; and thereby to provide a clinical specific reference values
      to determine the removal length for intestinal tract resection. METHODS:
      Immunohistochemistry technique was applied to detect the CR, c-kit, GDNF, BMP-2,
      alpha-SMA, and S-100 protein in specimens of atretic, proximal, and distal
      intestine from 25 cases of intestinal atresia and samples of intestinal walls
      from 10 non-atresia control specimens. The alteration of the enteric nervous
      system, nerve growth and its regulatory factors, the interstitial cells of Cajal
      (ICCs), and the enteric muscle system were examined, with particular attention
      being paid to pathological changes and the lesion area. RESULTS: The expression
      of all of the abovementioned 6 proteins in the proximal side of the atresia was
      significantly lower than in control group. The expression of the abovementioned
      proteins tended to be higher farther away from the atresia site. The expressions
      of both GDNF and BMP-2 had returned to normal level at 10 cm proximal to the
      atresia site, whereas the expressions of CR, c-kit, alpha-SMA, and S-100 protein
      only returned to normal at 15 cm proximal to the atresia site. On the distal
      side, the expression of all 6 markers at 3 cm distal to the atresia site was
      normal. CONCLUSION: Pathological deterioration of the myenteric ganglia, nerve
      growth factor, and ICCs are the causes of intestinal motility disorders after the
      surgical repair of intestinal atresia. Our data support resecting an intestinal
      segment extending from 15 cm proximal to 3 cm distal to the atretic segment. In
      proximal jejunal atresia, when it is not possible to resect 15 cm, we suggest
      resecting as much of the hypertrophic proximal intestine as possible. Based on
      our data, we believe this surgical practice could improve postoperative
      dysmotility in these patients.

PMID- 24094963
TI  - Perioperative outcome of laparoscopic Roux-en-Y gastric bypass: a children's
      hospital experience.
AB  - BACKGROUND/PURPOSE: To evaluate the perioperative safety of laparoscopic Roux-en
      Y gastric bypass (LRYGB) in a freestanding children's hospital setting. PATIENTS
      AND METHODS: Perioperative (<90 days) clinical complications of 77 consecutive
      patients (mean age 16.8 +/- 2.1 years: mean BMI 59.4 kg/m(2), 68% female), who
      underwent LRYGB at Cincinnati Children's Hospital from 2002 to 2007 were
      examined, using standardized data collection forms that were created specifically
      for use in this study. RESULTS: No mortality or conversion to open surgery was
      observed. Intraoperative complications were uncommon (3%). No anesthetic
      complications or transfusion requirements were observed. Median hospital stay was
      3 days. Twenty-two percent of subjects had a complication from discharge to 30
      days, while 13% experienced a complication between 31 and 90 days. The common
      types of postoperative complications included gastrojejunal anastomotic stricture
      (17%), leak (7%), dehydration (7%), and small bowel obstruction (SBO; 5%).
      Reoperation was required in 9 subjects. Operating time significantly decreased as
      the number of cases performed increased. CONCLUSIONS: LRYGB in this case series
      of adolescents was associated with a low rate of intraoperative complications,
      with an increased rate over the ensuing 90 days. These events can be successfully
      managed, even in super obese adolescents.

PMID- 24094964
TI  - Down-regulation of MeCP2 in Hirschsprung's disease.
AB  - BACKGROUND/PURPOSE: Hirschsprung's disease (HSCR) is a congenital disorder
      characterized by the absence of intramural ganglion cells which are highly
      associated with impaired proliferation and migration of neural crest cells.
      Whether methyl CpG binding protein 2 (MeCP2) is related with HSCR still remains
      unknown. This study investigates the involvement of MeCP2 in HSCR. METHODS:
      Quantitative real time PCR and western blot were used to detect the expression
      level of MeCP2 both in the aganglionic/diseased segment and the ganglionic/normal
      segment. In vitro assays we used siRNAs to knock-down the expression of MeCP2 in
      SH-SY5Y cell lines, and furthermore, MTT and transwell assays were used to detect
      the proliferation and migration ability, respectively. In addition, bisulfite
      sequencing (BSP) and miRNA analysis were used to examine why MeCP2 is decreased
      in HSCR samples. RESULTS: MeCP2 exhibited a lower expression level in tissues of
      HSCR patients compared with the controls. The down-regulation may also suppress
      the proliferative ability of the cells. However, there was no significant
      difference in the MeCP2 methylation level between cases and controls. Similarly,
      there was no difference between cases and controls in miRNA-34b (miR-34b) which
      is predicted to regulate MeCP2 through complementary binding to the 3'
      untranslated region of MeCP2. CONCLUSION: Our results indicated that an aberrant
      decreased level of MeCP2 may play an important role in the pathogenesis of HSCR.

PMID- 24094965
TI  - Base deficit correlates with mortality in pediatric abusive head trauma.
AB  - BACKGROUND/PURPOSE: Children suffering from abusive head trauma (AHT) have worse
      outcomes compared to non-AHT, but the reasons for this are unclear. We
      hypothesized that delayed medical care associated with AHT causes prolonged pre
      hospital hypotension and hypoxia as measured by admission base deficit (BD), and
      that this would correlate with outcome. METHODS: We performed a 10-year
      retrospective chart review of children admitted for AHT at two academic level-I
      trauma centers. Statistics were performed using Student's t test, chi-square
      analysis, and multivariate logistic regression, and considered significant at p <
      0.05. RESULTS: Four-hundred twelve children with AHT were identified, and
      admission BD was drawn for 148/412 (36%) children, including 104 survivors and 44
      non-survivors. Non-survivors had significantly higher BD compared to survivors
      (12.6 +/- 1.6 versus 5.3 +/- 0.6, p < 0.001). Non-survivors were more likely to
      be intubated pre-hospital and get cardiopulmonary resuscitation (CPR) (p <
      0.001). Mortality increased with rising BD, according to CPR status. There was no
      difference in patterns of brain injury between survivors and non-survivors (p >
      0.05). CONCLUSIONS: BD correlates with mortality in children suffering severe
      AHT. Non-survivors are also more likely to be intubated pre-hospital and require
      CPR, with no difference in pattern of brain injury, suggesting that secondary
      injury is a major determinant of outcome in severe AHT.

PMID- 24094966
TI  - Calretinin and microtubule-associated protein-2 (MAP-2) immunohistochemistry in
      the diagnosis of Hirschsprung's disease.
AB  - BACKGROUND/PURPOSE: Identifying ganglion cells by rectal suction biopsy is a
      basic diagnostic tool for the diagnosis of Hirschsprung's disease (HD). However,
      the difficult interpretation of conventionally processed slides often
      necessitates ancillary staining methods. The aim of this study was to evaluate
      the usefulness of calretinin and microtubule-associated protein-2 (MAP-2)
      immunohistochemistry in the diagnosis of HD. METHODS: We analyzed 52 rectal
      suction biopsy specimens (37 from 15 HD patients and 15 from 7 non-HD patients)
      for ganglion cells with calretinin and MAP-2 immunohistochemistry. We also
      analyzed full-thickness, frozen biopsy samples obtained from 15 HD patients who
      underwent surgery utilizing calretinin and MAP-2 immunohistochemistry. RESULTS:
      Both calretinin and MAP-2 positively stained ganglion cells in the submucosal
      plexus of the ganglionic bowel but not aganglionic bowel. Calretinin usually
      stained ganglion cell cytoplasm and nuclei more intensely than MAP-2, which only
      stained cytoplasm. No nerve fiber staining in the submucosal layer was observed
      for either antibody. In 21.1% (11/52) of samples, calretinin and MAP-2 staining
      found ganglion cells which were reported not to have ganglion cells in the
      original surgical pathology reports. Immunohistochemical staining for calretinin
      using paraffin-embedded tissue sections after cryostat sections clearly
      demonstrated decreased staining intensity compared to MAP-2. CONCLUSION:
      Calretinin and MAP-2 are useful diagnostic markers for diagnosing HD in rectal
      suction biopsies. These complementary methods could ameliorate the diagnostic
      difficulties associated with HD.

PMID- 24094967
TI  - The challenge of measuring quality of life in children with Hirschsprung's
      disease or anorectal malformation.
AB  - PURPOSE: The aim of the present study was to assess, after adaptation to French,
      the only specific quality of life (QoL) instrument for children with
      Hirschsprung's disease or anorectal malformation, the Hirschsprung's
      disease/Anorectal Malformation Quality of Life questionnaire (HAQL), in order to
      get a standardized QoL evaluation instrument that could further be used to help
      health care improvement. METHODS: The study was conducted in three teaching
      hospitals, including the French reference center for anorectal and pelvic
      malformations. After adaptation to French, QoL questionnaires were sent to the
      children and proxies. The questionnaire was mailed to 280 families. Psychometrics
      properties of the questionnaires (validity and reliability) were analysed from
      120 proxy and 96 child questionnaires. RESULTS: The HAQL with the original
      structure was not acceptable. Exploratory steps led to a clinically pertinent
      structure that had acceptable fit and good validity and reliability properties.
      The final structure pools physical symptoms (continence, discomfort) and
      psychosocial dimensions (general well-being, social and emotional functioning) of
      QoL. CONCLUSION: The final structure, despite the disadvantage of being a new
      structure, allows assessment of QoL in this population and has the advantage of
      being shorter and validated on the clinical postoperative questionnaire from the
      Krickenbeck international consensus.

PMID- 24094968
TI  - Outcome of antegrade continent enema (ACE) procedures in children and young
      adults.
AB  - OBJECTIVE: Intractable incontinence affects a large number of children and young
      adults in the US. The goal of this study is to evaluate the long-term outcomes of
      surgical access for administration of antegrade continence enemas (ACE) in
      affected children and young adults. METHODS: Patients who underwent surgical
      procedure to enable administration of ACE from 1994 to 2011 were retrospectively
      reviewed. Data collected included patient demographics, primary diagnosis,
      surgical technique, conduit used, complications, follow-up duration, and social
      continence. RESULTS: Sixty eighty patients underwent surgery to enable ACE; mean
      follow up was 61 months. Enteral conduit (EC) was performed in 19 patients, tube
      cecostomy catheters (CC) in 49. Meningomyelocele was diagnosed in 60% of
      patients. Mean age was 11 (1.67-53) years. Complications included tube
      dislodgement (43%), granulation tissue (46%), site infection (13%), leakage
      (32%), break in the tube (6%) and tract stenosis (6%). Complete social continence
      was achieved in 68%, partial continence was achieved in 29%, and no benefit was
      achieved in 3% of patients. The rate of complications and incontinence resolution
      following CC was 78% and 66%, and following EC 89% and 74%. The differences were
      not statistically significant. CC patients developed granulation tissue more
      frequently (53%) and leaks of fecal material less frequently (20%) compared to EC
      patients (26% and 53%) (p < 0.05 and < 0.01). Although children 7 years or
      younger developed more overall complications (94%) than older patients (69%; p <
      0.05), there was not a significant difference in the frequency of any one
      complication or in the rate of continence, between the two groups. Multivariate
      analysis showed that EC is three times more likely to be complicated by fecal
      leakage. CC patients are at greater risk to develop granulation tissue (p <
      0.05). CONCLUSIONS: Most patients achieved social continence and improved hygiene
      with the aid of ACE. Younger children also benefited greatly from institution of
      ACE. CC was associated with fewer major complications such as leak of fecal
      contents than EC but required regular tube changes.

PMID- 24094969
TI  - Outcomes following Malone antegrade continence enema and their surgical
      revisions.
AB  - BACKGROUND/PURPOSE: The Malone antegrade continence enema (MACE) channel is an
      effective means to manage patients with neurogenic bowel; however, complications
      may occur that may require surgical revision. Specific reports of the outcomes of
      these interventions are limited. We describe our clinical results following
      revision of MACE. METHODS: We retrospectively identified patients undergoing MACE
      revision for at our institution between 1997 and 2009. Type of MACE (in situ
      appendicocecostomy (AC = 247), ileocecostomy (IC = 25), cecal flap (CF = 10))
      performed was recorded, time from creation to revision, site of revision, and
      need for repeat surgical revision were recorded. RESULTS: Of a total of 282
      patients that underwent creation of MACE during the study period, 49 patients
      (17%) required surgical revision. Of these 49 patients, 42 had undergone AC, four
      had IC and three had CF. Mean time from MACE creation to revision was 19 months.
      Sixty-eight revision procedures were performed in the 49 patients. Skin level or
      endoscopic procedures accounted for 52/67 (78%) procedures. Sixteen patients
      (33%) required more than one revision and three patients (6%) required more than
      two procedures. CONCLUSIONS: Skin level revisions accounted for over three
      fourths of MACE revisions. In our series, two thirds of patients requiring
      revision required only a single procedure, but one third required more than one
      revision.

PMID- 24094970
TI  - The protective effect of Cold-inducible RNA-binding protein (CIRP) on testicular
      torsion/detorsion: an experimental study in mice.
AB  - PURPOSE: To evaluate the expression of Cold-inducible RNA-binding protein (CIRP)
      in torsion/detorsion of the testes in different phases and demonstrate the
      protective effect of CIRP on testicular injury after torsion/detorsion (T/D) in
      an experimental mouse model. METHODS: Twenty-four male BALB/c mice were divided
      randomly into 8 groups: normal control group (N), sham-operated group (S),
      torsion 2 h group (T2h), torsion/detorsion 12 h group (T/D12h), and T/D24h,
      T/D48h, T/D72h, and T/D96h groups. The testes were examined for the expression
      levels of CIRP. Another 32 male BALB/c mice were divided randomly in to 4 groups:
      normal control group (N), T/D group, T/D+pcDNA3.1 group, and T/D + pcDNA3.1-CIRP
      group. The plasmids were transfected into testes with in vivo-jetPEI. After 3
      days, morphological changes, mean seminiferous tubule diameter (MSTD), and the
      number of the germ cell layers were observed. Superoxide dismutase (SOD)
      activity, the levels of malondialdehyde (MDA), and Bcl-2/Bax ratios were studied
      in the different groups. RESULTS: Compared with the N and S groups, the
      expression of CIRP in the T2h group was down-regulated. In T/D groups, the levels
      of CIRP were reduced in a time dependent manner. Compared to T/D and T/D+pcDNA3.1
      group, the MSTD, number of the germ cell layers, SOD activity, and Bcl-2/Bax
      ratio increased in T/D + pcDNA3.1-CIRP group, while the level of MDA decreased.
      CONCLUSIONS: The results of our study have shown that down-regulated CIRP is
      involved in testicular injury after testicular torsion/detorsion. Up-regulation
      of the expression of CIRP may reduce the damage caused by torsion/detorsion,
      possibly by preventing germ cell oxidative stress and apoptosis.

PMID- 24094971
TI  - Current diagnosis and management of urachal remnants.
AB  - PURPOSE: The purposes of this study are to review our experience with patients
      who were found to have urachal remnants. We discuss their diagnosis and
      management and we also evaluate post-operative complications in our cohort of
      patients with this entity. METHODS: We performed a retrospective review of all
      patients diagnosed with a urachal remnant (UR) between January 2006 and December
      2010. Patient variables included age, gender, presenting symptoms and signs,
      diagnostic modality, and type of urachal remnant. Operative management, post
      operative complications, and non-operative follow-up were abstracted. RESULTS: We
      identified 103 pediatric patients with either a urachal cyst (n = 38), urachal
      diverticulum (n = 13), urachal sinus (n = 11), patent urachus (n = 21), or a non
      specific atretic urachal remnant (n = 20). Seventy-eight patients had symptomatic
      URs. Thirty-four symptomatic patients underwent surgical excision of the UR and
      44 symptomatic patients were observed. Eighteen URs were incidentally diagnosed
      in asymptomatic patients, none of whom underwent surgical excision. In 7 patients
      symptoms could not be determined from the records. No patients with non-specific
      atretic remnants were operated upon. Nineteen of the observed patients were
      reimaged subsequently. In fifteen (78.9%) of these patients, the URs had resolved
      spontaneously. None of the patients who were observed required subsequent
      excision of the UR. Post-operative complications occurred in 14.7% of patients in
      whom URs were excised. CONCLUSION: Review of our patients diagnosed with URs
      indicates there is a subset of patients in whom spontaneous resolution could be
      expected. Complications are not uncommon after surgical excision.

PMID- 24094973
TI  - Inguinal hernias containing the uterus: a case series of 7 female children.
AB  - BACKGROUND: Hernia uteri inguinale (HUI), or uterus-containing inguinal hernia,
      is an extremely rare condition in which the uterus and uterine adnexa are found
      in the inguinal hernial sac in female infants. The uterus may be free within the
      sac adherent to the wall by adhesions or a true sliding component. However, in
      true sliding-type HUI, one of the walls of the hernia sac is formed by the uterus
      itself. PATIENTS AND METHODS: The medical records for all female children with
      inguinal hernia who were operated from 1999 through 2010 were reviewed
      retrospectively (n = 3100). RESULTS: Among these patients, we identified seven
      cases of HUI in infants with a normal female karyotype. The incidence of HUI was
      0.23%. Patients were discharged on the postoperative 1st day with no
      complications. CONCLUSIONS: Surgeons should be aware of the possibility of
      presence of the uterus or another organ in the hernial sac in phenotypic female
      children, and sliding components should be replaced carefully into the abdomen to
      prevent any damage.

PMID- 24094972
TI  - Management of epididymal cysts in childhood.
AB  - BACKGROUND: A retrospective review was carried out to evaluate the clinical
      presentation of children with epididymal cysts (EC) and outcome of management at
      our institution. METHODS: There were 49 patients with EC in this series. The
      diagnosis of EC was made by physical examination and confirmed by ultrasound
      (US). RESULTS: The average age at presentation was 10.7 years (2 months-16
      years). Scrotal mass (n: 22) and pain (n: 21) were the most frequent symptoms.
      Seven patients were lost to follow-up. The cysts were solitary in 32 patients and
      multiple in 10 patients. The mean value of cysts was 6.7 mm (2-20 mm). The cyst
      localisations were 22 in left, 16 in right, and bilateral in 4 patients. Complete
      involution of cysts was detected in 14 children. The average involution time was
      11.2 months (1-37 months). In 20 cases, a decrease in cyst size was found. Cyst
      excision was performed in 8 patients with persistent scrotal pain or no cyst
      involution observed during follow-up. CONCLUSION: Conservative management of
      epididymal cysts is practical. However, surgical excision is recommended in
      patients with intractable scrotal pain or if the cyst size does not seem to
      involute.

PMID- 24094974
TI  - An electrophysiologic evaluation of whether open and laparoscopic techniques used
      in pediatric inguinal hernia repairs affect the genitofemoral nerve.
AB  - BACKGROUND: A prospective study was performed to evaluate the effect of inguinal
      hernia repairs on the genitofemoral nerve (GFN), and to compare postoperative
      electrophysiologic changes in the GFN of patients who had undergone either open
      or laparoscopic surgery. METHODS: Seventy patients with a mean age of 6.48 +/-
      3.49 were enrolled in the study. Either open or laparoscopic techniques were used
      to operate on the patients' inguinal hernias. In all cases, bilateral GFN motor
      responses were investigated electrophysiologically using surface electrodes on
      three occasions: preoperatively, in the first month, and third month
      postoperatively. t-Tests were used to compare changes in the GFN. RESULTS:
      Preoperative mean latency of the GFN in all groups was found to be significantly
      prolonged on the hernia side, compared with the non-hernia side (P = 0.01).
      Although no difference was observed in the latency levels of the GFN on the
      operated side at the preoperative and early postoperative stages, GFN latency
      levels decreased significantly in the late postoperative period in the
      laparoscopic group (P < 0.05). In the late postoperative period, amplitudes of
      GFN motor responses were significantly higher in the laparoscopic group than the
      open repair group (0.91 +/- 0.11 mV and 0.57 +/- 0.053 mV, respectively; P <
      0.05). CONCLUSION: Preoperative prolonged latency of GFN on the hernia side is
      likely to occur due to the pressure on the nerve caused by the hernia mass. By
      surgically removing the hernia mass, this buildup of pressure is prevented,
      decreasing the latency of the GFN. The significantly higher motor response
      amplitudes and decreased latency in the late postoperative stage for the
      laparoscopic group may be due to the fact that this technique is less invasive.

PMID- 24094975
TI  - Effect of P/E-selectin blockage on antisperm antibody development and
      histopathological alterations in experimental orchitis.
AB  - AIM: This study aimed to evaluate the effect of P/E-selectin blockage on
      antisperm antibody (ASA) development and histopathological alterations in
      experimental orchitis. MATERIALS AND METHODS: Thirty-six Wistar albino-type male
      rats weighing 100-150 g were included in the study. Rats were allocated into six
      groups (n = 6) including control (CG), sham (SG), orchitis (OG), antimicrobial
      treatment (AG), P/E-selectin blockage (PESG), and both antimicrobial and P/E
      selectin treatment (TG) groups. In CG, serum samples were taken from the tail
      vein prior to the procedure and followed by extraction of both testes. In SG, 1
      ml of saline solution was injected in testicular parenchyma. OG was obtained by
      injecting 0.1 ml 106 cfu/ml Escherichia coli (0:6 strain) and 1 ml saline
      solution into the right testes. AG received ciprofloxacin (50 mg/kg/day) twice a
      day through gastrogavage 24 hours after generating orchitis. In PESG, P/E
      selectin antibody (100 MUg) was administered intravenously via the tail vein 24
      hours after the induction of orchitis. Finally, both ciprofloxacin and P/E
      selectin antibody were administered in TG 24 hours after the induction of
      orchitis for 14 days. At the end of treatment, 1 ml of serum sample was obtained
      to evaluate the ASA, P-selectin and E-selectin levels. In order to evaluate
      spermatogenesis (Johnsen score) and testicular injury (Cosentino score), both
      testes were extracted at the end of the 14th day. RESULTS: In orchitis-induced
      groups (OG, ATG, PSEG, TG), ASA levels were significantly increased at the 14th
      day when compared to SG (p < 0.05). In TG, ASA levels were decreased when
      compared to AG. However, similar alteration in ASA levels was not detected in
      PSEG (p > 0.05). In OG and AG, P-selectin levels were decreased at the 14th day
      when compared to levels observed on 0 day (p < 0.05). E-selectin levels on 0 day
      showed that each group had higher levels of E-selectin when compared to CG (p >
      0.05). There was no significant difference regarding E-selectin when compared to
      CG (p > 0.05). No significant differences regarding E-selectin levels were
      detected on the 0th and 14th days between AG and CG (p > 0.05). When the
      Cosentino and Johnsen scores were compared among groups, TG and PSEG has
      decreased scores of Cosentino than OG on the right testicle (p < 0.05). In
      contrast, an increased Johnsen score was detected in TG and PSEG when compared to
      OG (p < 0/05). No significant difference was detected for both Cosentino and
      Johnsen scores on the left testicle (p > 0.05). There was no difference with
      regard to the right and left testicular injury in TG. In P/E-blocked groups,
      decreased histopathological alterations were observed in the contralateral
      testis. CONCLUSION: P/E-selectin blockage may reduce ASA production after
      orchitis when combined with antimicrobial treatment. P/E-selectin blockage not
      only has a protective effect on blood-testis barrier but also decreases the
      histopathological alterations in both the affected and contralateral testis.
      Histopathological parameters of spermatogenesis may also be prevented by P/E
      selectin blockage in experimental orchitis.

PMID- 24094976
TI  - Which surgery for drooling in patients with cerebral palsy?
AB  - BACKGROUND: Surgery for drooling in patients with cerebral palsy should not
      produce xerostomia in order not to deteriorate speech, taste, or the status of
      oral hygiene. It must be a compromise between drooling and quality of life. The
      purpose of the present report is to describe our surgical strategy that respects
      the above principles. MATERIALS AND METHODS: Patients were initially operated on
      depending on the drooling severity. The results were evaluated according to the
      frequency of residual drooling and the Thomas-Stonel and Greenberg
      classification. Quantitative assessment was proposed 6 months after surgery. The
      data have been compared using the nonparametric Wilcoxon matched-pairs test.
      RESULTS: Thirty-five patients underwent surgery between 1991 and 2012. Owing to
      incomplete data, only 31 patients could be included, aged 5 to 24 years (mean: 12
      years). All patients underwent surgery on the submandibular duct. Only 16
      patients underwent a simultaneous surgery on the parotid duct. Six patients were
      reoperated: 3 because of an insufficient result and 3 because of a surgical
      complication. Changes/Day ranged from 1 to 7 (median: 3) before surgery and 0 to
      2 (median: 1) after surgery (p < 0.01). Number of bibs/day ranged from 0 to 30
      (median: 4) before surgery and 0 to 4 (median: 1) after surgery (p < 0.01). No
      dental deterioration and no caries occurred after surgery. CONCLUSION: Good
      results for drooling can be obtained with a simple surgical procedure on the
      submandibular ducts, maintaining quality of life, avoiding deterioration of
      speech, taste, and the status of oral hygiene.

PMID- 24094977
TI  - A review of postoperative feeding regimens in infantile hypertrophic pyloric
      stenosis.
AB  - Infantile hypertrophic pyloric stenosis is a condition well known to pediatric
      surgeons. Postoperative length of hospital stay is a financial concern and
      remains a potential target for reduction in hospital costs. Ultimately, these
      costs are directly affected by the ability to effectively advance postoperative
      enteral nutrition. This review will serve to: 1) identify clinically relevant
      postoperative feeding patterns following pyloromyotomy, 2) review the relevant
      literature to determine an optimal feeding pattern, and 3) identify possible
      preoperative predictors that may determine the success of postoperative feeding
      regiments. 

PMID- 24094978
TI  - High-performance polymer solar cells with solution-processed and environmentally
      friendly CuOx anode buffer layer.
AB  - Highly efficient polymer solar cells (PSCs) are demonstrated by introducing
      environmentally friendly CuOx as hole extraction anode buffer layer. The CuOx
      buffer layer is prepared simply via spin-coating 1,2-dichlorobenzene solution of
      Copper acetylacetonate on the ITO substrate and thermal transformation (at 80 
      degrees C) in air. Remarkable improvements in the open-circuit voltage (Voc) and
      short-circuit current density (Jsc) of the PSCs could be achieved upon the
      introduction of CuOx buffer layer. The study about the effect of CuOx interfacial
      layer on the device resistances demonstrates that insertion of CuOx layer can
      decrease the whole resistance of the PSCs. For the devices based on P3HT:PCBM,
      the power conversion efficiency (PCE) was increased from 2.8% (the reference
      device without buffer layer) to 4.1% via introduction of CuOx hole extraction
      layer. The PCE of the PSC was further increased to 6.72% when ICBA used as an
      alternative acceptor to PCBM. The much higher PCE of 7.14% can be achieved by
      adopting PBDTTT-C, a low band gap conjugated polymer, as donor material. The
      results demonstrate that CuOx has great potential as a hole extraction material
      for highly efficient PSCs.

PMID- 24094981
TI  - Resistin, an adipokine, may affect the improvement of insulin sensitivity in the
      metabolic syndrome patient treated with metformin.
AB  - The metabolic syndrome (MS) is a cluster of metabolic disorders arising from
      insulin resistance, characterized by the presence of central obesity, impaired
      fasting glucose level, dyslipidemia and hypertension. As the first-line
      medication, metformin is commonly used for MS to reduce insulin resistance.
      Comparing with rosiglitazone, metformin does not increase cardiovascular
      mortality risk in patients with MS. However, metformin is not good enough in
      improving insulin sensitivity. Its molecular mechanism is still not clear. Recent
      studies have demonstrated that resistin, an adipokine, could induce IR by both
      AMPK-dependent and AMPK-independent pathways. Though there were conflicting
      findings of resistin in metabolic syndrome or type 2 diabetes mellitus in
      different studies, resistin was significant decreased in the rosiglitazone
      treated patients than in the metformin-treated patients in most of studies. Here,
      we hypothesized that resistin, an adipokine, may affect the improvement of
      insulin sensitivity in the metabolic syndrome patient treated with metformin.
      This hypothesis could explain why rosiglitazone is superior to metformin in
      enhancement of insulin sensitivity. 

PMID- 24094980
TI  - DNA quantification of exfoliated colonocytes as a novel screening tool for
      colorectal cancer.
AB  - AIMS: Colorectal cancer (CRC) sheds viable cells in the mucocelluar layer
      overlaying the colonic mucosa which travels distally alongside the faecal stream.
      These cells can be retrieved from the surface of the rectal mucosa. DNA
      quantification of these cells may be a marker of CRC, assessment of which was aim
      of this study. METHODS: A prospective double-blinded study of 467 consecutive
      patients referred with symptoms suggestive of CRC. Cells were collected from the
      surface of the rectal mucosa and total DNA quantified. DNA scores were compared
      with outcome after subjects had completed bowel investigations. Analysis of
      receiver operating characteristic (ROC) curves was performed to determine the
      optimum cut-off point for a positive result. RESULTS: 107 of the 467 patients
      were excluded due to; excessive faecal contamination of samples (n = 84);
      declined investigations (n = 17); inappropriate referral (n = 5); unfit (n = 1).
      263 patients had lower GI endoscopy; 89 CT colonography and 8 barium enema. The
      diagnosis were; CRC (n = 23), inflammatory bowel disease (IBD) (n = 7),
      adenomatous polyps (AP) (n = 20) and no significant abnormality detected (n =
      310). ROC analysis revealed that sensitivities at a specificity of 60% for
      detecting CRC were 91.3%; for CRC and IBD 86.7%; and for CRC, IBD and AP 72.0%.
      CONCLUSION: In symptomatic patients DNA quantification of cells retrieved from
      the surface of the rectal mucosa is sensitive for the detection of CRC. Although
      faecal contamination is a limitation of this technique, refinement and
      application of other molecular tests hold promise for a better non invasive
      method for the detection of CRC.

PMID- 24094979
TI  - Determinants of pain treatment response and nonresponse: identification of TMD
      patient subgroups.
AB  - The purpose of the present study was to determine if we could identify a specific
      subtype of temporomandibular disorder (TMD) pain patients that does not respond
      to treatment. Patients were 101 men and women with chronic TMD pain recruited
      from the community and randomly assigned to 1 of 2 treatment conditions: a
      standard conservative care (STD) condition or a standard care plus cognitive
      behavioral therapy condition (STD + CBT) in which patients received all elements
      of STD but also received cognitive-behavioral coping skills training. Growth
      mixture modeling, incorporating a series of treatment-related predictors, was
      used to distinguish several distinct classes of responders or nonresponders to
      treatment based on reported pain over a 1-year follow-up period. Results
      indicated that treatment nonresponders accounted for 16% of the sample and did
      not differ from treatment responders on demographics or temporomandibular joint
      pathology, but that they reported more psychiatric symptoms, poorer coping, and
      higher levels of catastrophizing. Treatment-related predictors of membership in
      treatment responder groups versus the nonresponder group included the addition of
      CBT to STD, treatment attendance, and decreasing catastrophization. It was
      concluded that CBT may be made more efficacious for TMD patients by placing
      further emphasis on decreasing catastrophization and on individualizing care.
      PERSPECTIVE: This article provides evidence that the TMD chronic pain population
      is heterogeneous and that a subsample of patients will be unresponsive to
      standard or psychosocial approaches. The addition of CBT to treatment may be
      helpful for this group, but new individualized approaches will be needed to treat
      all patients effectively.

PMID- 24094982
TI  - Role of perioperative low dose vaginal oestrogens in improving the outcomes of
      pelvic organ prolapse surgery.
AB  - Pelvic organ prolapse (POP) is the most common gynaecological disorder requiring
      surgical treatment in postmenopausal women. Surgical treatment of POP might
      include anterior or posterior vaginal repair, vaginal hysterectomy, vault
      fixation procedures like sacrocolpopexy and sacrospinous fixation. Complications
      of POP surgery include excessive bleeding, visceral injuries, postoperative wound
      infection, urinary tract infection (UTI), sexual dysfunction secondary to vaginal
      scarring and recurrence. Postmenopausal vaginal atrophy may increase the risk of
      visceral injuries due to thinning of vaginal wall and also increases the risk of
      surgical site wound infections due to alteration of vaginal flora and urinary
      tract infections (UTI). Use of vaginal low dose oestrogens to treat atrophy of
      the vagina may improve the subjective cure rates and minimise surgical site wound
      infections by altering the vaginal flora to premenopausal levels. To date there
      has not been any data on the outcomes of POP surgery when low dose vaginal
      oestrogens are used perioperatively. Hence we want to study the effectiveness of
      vaginal low dose oestrogen on the outcome of POP surgery in postmenopausal women.

PMID- 24094983
TI  - Pre-treatment with calcium prevents endothelial cell activation induced by
      multiple activators, necrotic trophoblastic debris or IL-6 or preeclamptic sera:
      possible relevance to the pathogenesis of preeclampsia.
AB  - INTRODUCTION: A hallmark of preeclampsia is endothelial cell
      dysfunction/activation in response to "toxins" from the placenta. Necrotic
      trophoblastic debris (NTD) is one possible placental toxin and others include
      inflammatory cytokines. Calcium supplementation appears to protect "at-risk"
      women from developing preeclampsia by an unknown mechanism. In this study we
      investigate whether the addition of high levels of calcium to endothelial cells
      prior to their exposure to the preeclampsia-associated activators could reduce
      the endothelial cell activation. METHODS: NTD was harvested from 1st trimester
      placental explants. Endothelial cells were treated with varied concentrations of
      calcium prior to exposure to NTD, IL-6 or preeclamptic sera or low levels of
      calcium. Activation was monitored by quantifying endothelial cell-surface ICAM-1
      by ELISA or U937 adhesion to endothelial cells. The activity of endothelial cell
      nitric oxide synthetase was blocked with L-NAME. RESULTS: Pre-treatment with
      increasing concentrations of calcium inhibited the activation of endothelial
      cells in response to NTD or IL-6 or preeclamptic sera. Inhibiting nitric oxide
      synthetase, using L-NAME, reduced the ability of high calcium levels to protect
      endothelial cell activation. Pre-treatment with calcium did not prevent
      endothelial cell activation induced by the reduction of the levels of calcium but
      additional calcium treatment did prevent endothelial cell activation induced by
      low calcium. CONCLUSION: Our results demonstrate calcium supplementation may
      prevent the activation of the endothelium in response to activators. These
      results may partially explain the benefits of calcium supplementation in the
      reduction of risk for developing preeclampsia and provide in vitro mechanistic
      support for the use of calcium supplementation in at-risk women.

PMID- 24094984
TI  - [Frequent visitors to psychiatric emergency service: Demographical and clinical
      analysis].
AB  - INTRODUCTION: Frequent visitors of psychiatric emergency wards are an important
      health care problem. Previous studies underlined that 2 % to 9 % of patients
      induce 15 % to 33 % of total clinical activity. Those patients have chronic and
      severe mental illness such as schizophrenia, associated with social and financial
      difficulties. OBJECTIVE: The aim of this study was to describe demographic and
      clinical characteristics of frequent visitors to a psychiatric emergency ward in
      a French Academic hospital over 6years in comparison to non-frequent visitors.
      METHODS: The study is based on a retrospective review of the psychiatric
      emergency wards' administrative and medical computer databases; data that
      included demographic, financial, clinical, and management information. During
      this 6-year study, the psychiatric ward recorded 16,754 care episodes for 8800
      different patients. We compared frequent visitors with other visitors using
      univariate and multivariate analyses. Frequent visitors were defined by a number
      of visits greater than 2 of the mean standard deviation. RESULTS: Two percent of
      patients (n=192) had nine or more visits during the period. These patients caused
      21 % of the total number of the visits. In the univariate analysis, the most
      significant reasons for referral in frequent visitors versus others (P<0.001)
      were: more frequent anxiety (37.6 % vs. 32.1 %), less frequent disruptive
      behavior (8.4 % vs. 12.9 %), depression (7.8 % vs. 17.2 %) and suicide attempt
      (4.5 % vs. 11.1 %). Factors associated with frequent visitors (P<0.001), after
      including all significant or confounding variables (multivariate analysis), were:
      schizophrenia and schizophrenia spectrum disorders (OR=29.5, IC: 11.4-76), DSM-IV
      cluster B personality disorders (OR=5.5, IC: 3.6-8.4), mental and behavioral
      disorders due to psychoactive substance use (OR=4.6, IC: 3.1-7), financial
      assistance through social government programs (OR range: 9.1-2.4, all
      significant) and being homeless (OR=2.7, IC: 1.8-4). Factors associated with non
      frequent visitors were mood disorders (OR=0.07, IC: 0.03-0.19) and neurotic,
      stress-related, and somatoform disorders (OR=0.14, IC: 0.05-0.4). Sex and age
      were not significant in multivariate analysis. DISCUSSION: This study identifies
      significant demographic and clinical factors associated with frequent visits in
      psychiatric emergency ward in accordance with the large majority of previous
      studies. We found that psychotic disorders or schizophrenia were the main
      diagnosis of these patients. Moreover, precariousness (homeless, financial
      assistance) is an important demographic factor associated with recurrence.
      However, contrary to numerous studies, we found no effect of sex or age. Due to
      this important economical and clinical burden, more specific care and alternative
      solutions to emergency care have to be proposed to this population of patients.

PMID- 24094985
TI  - [Recurrent voluntary ingestion of metallic objects in prison by a female
      patient].
AB  - INTRODUCTION: Recurrent and intentional ingestion of metallic objects is a rare
      but important phenomenon. It has attracted great interest among mental health
      professionals over the last decades. However, this issue is rarely reported in
      the literature. A deep exploration of its clinical and specific
      psychopathological aspects remains limited. CASE REPORT: We report the case of a
      32-year-old female patient, who was sentenced to 20 years in prison for homicide
      against her cousin, the daughter of an uncle who had raped her when she was 14.
      This affair was hushed by the patient's family and the patient was submitted to
      several acts of abuse by her family. Following her incarceration, she repeatedly
      ingested metallic objects requiring repeated admissions in a department of
      surgery for endoscopic extractions or surgical interventions. She impulsively
      ingested more than 30 times various metallic objects such as wire, razor blades,
      spoons, etc., under the pressure of impulsiveness and massive anxiety. Voluntary
      metal ingestions, associated with iterative self-mutilation behaviors, took place
      within the framework of a borderline personality disorder, the incarceration and
      the conditions of imprisonment playing a role in initiating and retaining the
      behavior. CONCLUSION: Through this case report, we examine the specific
      psychiatric aspects of intentional ingestion of metallic objects in order to
      better understand this behavior.

PMID- 24094986
TI  - [Predicting bipolar disorder: what can we learn from prospective cohort
      studies?].
AB  - INTRODUCTION: Bipolar disorder (BD) is a life course illness; and there is
      increasing awareness of the many personal, social and economic consequences of
      the illness in older adults. However, it is important to emphasize that BD
      usually begins in late adolescence or early adulthood and 75 % cases have a first
      episode in this age period. This early onset and the associated level of
      disability mean that BD is the 4th leading cause of global disease burden in
      adolescents and young adults. Internationally, mental health services are
      increasingly striving to diagnose and treat BD as early as possible to try to
      prevent poor outcomes. In addition, researchers are using methods employed
      previously in psychosis studies as these may help us to recognise the earliest
      manifestations of BD. If it is possible to identify sub-threshold and 'ultra high
      risk' syndromes for BD, this might lead to new interventions that could target
      the prevention of first episodes of mania. One approach to understanding these
      risk syndromes is to examine prospective community cohort studies and BD
      offspring studies. METHODS: This paper reviews prospective cohort studies that
      identify robust risk factors in early illness onset, which was defined as age at
      onset of BD between 15-25 years. RESULTS: We found that although > 50 % of
      individuals who developed BD had developed a putative BD prodrome prior to 14
      years of age, this usually began with non-specific symptoms that overlap with
      similar presentations for those who later develop psychosis or severe depression.
      However, there are some features that seem to better identify groups with a BD
      "at-risk" syndrome. This syndrome is frequently composed of several factors such
      as mood lability, depressive episodes, prior anxiety, sleep and/or conduct
      disorders, attention and concentration impairment, altered energy patterns, and a
      family history of mania and/or depression. The course of these early predictors
      suggests the precursor syndromes are composed of mini-clusters of symptoms many
      of which are episodic and change over time. During the early phases of BD, most
      of the affective disturbances reported were depressive in polarity and started
      during adolescence, there were few manic or mixed or psychotic episodes with an
      onset before puberty. The pathogenesis of BD demonstrates a gradual progression
      from non-specific to more specific symptoms and then to frank BD features.
      CONCLUSION: Prospective community and offspring BD cohort studies are approaches
      that together can help us understand the evolution of BD and allow us to define
      the developmental pathways. Further, identifying subjects with BD "at-risk"
      syndrome using a clinical staging model may allow benign interventions to be used
      as first-line treatment - such as neuroprotective agents like essential fatty
      acids; second line treatments, with a less benign risk to benefit ratio should be
      reserved for severe or resistant cases.

PMID- 24094987
TI  - Treatment of sandal burns of the feet in children in a moist environment.
AB  - Burns to children's feet are often due to scalds, from hot tap water, as an
      infant's skin is thinner and hence more susceptible to a full-thickness injury.
      In Central Asia, and particularly in Uzbekistan, many episodes of burns take
      place at homes because of using sandal heaters. In the case of sandal burns of
      the foot, it usually is not only skin that is injured but also underlying
      tissues: subcutaneous fat, fasciae, muscles and even bones. Many controlled
      studies have confirmed that wounds heal more readily in a moist, physiological
      environment. After performing the toilet of burn wounds of the foot, we applied
      Dermazin cream on the affected areas and then the foot was placed onto a
      polyethylene packet of large size and fixed by a bandage. Measurement of wound
      water evaporation was performed every day post-burn. Surgery was usually
      performed 15-17 days after burn by applying a perforated skin graft or a 0.2-0.3
      mm-thick non-perforated skin graft. The procedures helped to improve the general
      condition of patients, shortened their stay in hospital and also reduced expenses
      and lessened joint deformities and contracture deformities. 

PMID- 24094988
TI  - Microscopic anterior foraminal decompression combined with anterior lumbar
      interbody fusion.
AB  - BACKGROUND CONTEXT: Anterior lumbar interbody fusion (ALIF) with percutaneous
      pedicle screw fixation (PPF) provides successful surgical outcomes to isthmic
      spondylolisthesis patients with indirect decompression through foraminal volume
      expansion. However, indirect decompression through ALIF followed by PPF may not
      obtain a successful surgical outcome in patients with isthmic spondylolisthesis
      accompanied by foraminal stenosis caused by a posterior osteophyte or foraminal
      sequestrated disc herniation. Thus far, there has been no report of foraminal
      decompression through anterior direct access in the lumbar spine. PURPOSE: This
      study aims to describe the new surgical technique of microscopic anterior
      foraminal decompression and to analyze the clinical outcomes and radiologic
      results of the microscopic anterior decompression during ALIF followed by PPF.
      STUDY DESIGN/SETTING: We conducted a multisurgeon, retrospective, clinical series
      from a single institution. PATIENT SAMPLE: This study was carried out from March
      2007 to July 2010 and included 40 consecutive patients with isthmic
      spondylolisthesis accompanied by foraminal stenosis caused by posterior
      osteophyte or foraminal sequestrated disc herniation undergoing microscopic
      anterior foraminal decompression during ALIF followed by PPF. OUTCOME MEASURES:
      The visual analog scales (VAS) of back and leg pain and the Oswestry disability
      index were measured preoperatively and at the last follow-up. METHODS:
      Postoperative computed tomography and magnetic resonance imaging measured whether
      decompression of neural structure had been made and morphometric change of the
      foramen and the amount of resected bone. Moreover, segmental lordosis, whole
      lumbar lordosis, disc height, and degree of listhesis were measured through X-ray
      examination before the operation and at the last follow-up; we also verified
      whether fusion had been achieved. RESULTS: Successful decompression was confirmed
      in both patients with foraminal stenosis caused by posterior osteophyte and those
      with foraminal sequestrated disc herniation. Clinically, compared with before the
      surgery, the VAS (leg and back) and the Oswestry disability index significantly
      decreased at the last follow-up (p=.000). With regard to radiology, at the last
      follow-up all patients had bone fusion on X-ray examination, and an increase in
      disc height, a reduction in the degree of listhesis, an increase in segmental
      lordosis, and an increase in whole lumbar lordosis were significant in both
      groups (p=.000) compared with before the surgery. Foraminal volume, foraminal
      width, and foraminal height also significantly increased postoperatively compared
      with before the operation (p=.000). The height, width, and dimension of resected
      body were 4.61+/-1.05 mm, 7.92+/-1.42 mm, 17.15+/-4.96 mm(2), respectively, in
      patients with foraminal stenosis caused by a posterior osteophyte, and 3.88+/
      0.92 mm, 6.8+/-1.29 mm, and 13.12+/-2.25 mm(2), respectively, in patients with
      foraminal sequestrated disc. CONCLUSIONS: The microscopic anterior foraminal
      approach provides successful foraminal decompression. Combined with ALIF and PPF,
      this approach shows a good surgical outcome in patients with isthmic
      spondylolisthesis accompanied by foraminal stenosis caused by a posterior
      osteophyte or those with foraminal sequestrated disc herniation.

PMID- 24094990
TI  - Polyostotic fibrous dysplasia involving the thoracic spine with myelopathy: case
      report and review of the literature.
AB  - BACKGROUND CONTEXT: Polyostotic fibrous dysplasia (PFD) seldom involves the
      thoracic spine and usually presents with back pain. PURPOSE: To describe an
      extremely rare presentation of an uncommon disease. STUDY DESIGN/SETTING: We
      present a case report from a university hospital. METHODS: We report a case of
      symptomatic thoracic PFD associated with myelopathy and pathologic fracture. A
      thorough search of PubMed/MEDLINE was performed for the terms "polyostotic
      fibrous dysplasia," "spine," and "neurological deficit." RESULTS: The patient was
      treated by posterior laminectomy, vertebroplasty, and pedicle screw fixation and
      fusion. Satisfactory results were achieved, and there were no complications.
      CONCLUSIONS: In the spine, PFD may lead to pathologic fracture and myelopathy
      even after adolescence. Vertebroplasty with or without decompression and fixation
      may be the appropriate option for cases with myelopathy.

PMID- 24094989
TI  - Extracorporeal shock wave therapy relieved pain in patients with coccydynia: a
      report of two cases.
AB  - BACKGROUND CONTEXT: Extracorporeal shock wave therapy (ECSWT) has been used
      widely for musculoskeletal conditions; however, no reports are available about
      its use for coccydynia. PURPOSE: Study the effect of ECSWT in relieving pain of
      coccydynia. STUDY DESIGN: Case report. METHODS: Extracorporeal shock wave therapy
      was used for two male patients, Patients 1 and 2, who failed to respond
      completely to other conservative management of coccydynia. Numerical pain scale
      (NPS) and visual analogue scale (VAS) were used to assess the pain. Consent to
      publish the data was obtained from both the patients. RESULTS: Before starting
      ECSWT, Patient 1 reported a pain intensity of 6/10 and 5.1/10 on NPS and VAS,
      respectively, whereas the intensity of pain in Patient 2 was 7/10 and 6.9/10 on
      NPS and VAS, respectively. Four weeks after ECSWT, Patient 1 reported complete
      relief of pain on NPS and VAS, whereas Patient 2 reported a pain intensity of
      1/10 and 0.8/10 on NPS and VAS, respectively. The same intensity of pain was
      reported by both patients after 12 months of follow-up. CONCLUSIONS:
      Extracorporeal shock wave therapy relieved pain of coccydynia in our patients.

PMID- 24094991
TI  - Acute spinal subdural hematoma with hemiplegia after acupuncture: a case report
      and review of the literature.
AB  - BACKGROUND CONTEXT: Subdural spinal hematoma (SDH) is a very rare entity;
      however, it can lead to serious complications resulting from injuries to the
      spinal cord and roots. Although acupuncture has been a popular method for the
      management of pain control, we encountered the first case of SDH after
      acupuncture. PURPOSE: The purpose of this case report was to present the first
      case of subdural hematoma after acupuncture and the reasons for the risks of
      blind cervical acupuncture. STUDY DESIGN: A case report and review of the
      previous literature are presented. METHODS: A 69-year-old man complained of
      progressive weakness in the right upper and lower extremities 2 hours after
      acupuncture on the cervical spine and back. The diagnosis was delayed because of
      unilateral weakness, and the symptom was initially misinterpreted as a transient
      ischemic attack because of no sensory change and pain and normal findings of two
      brain magnetic resonance imaging (MRI). RESULTS: Cervical MRI 36 hours after
      onset revealed acute hematoma from the C3-C5 level; hematoma showed an
      isointensity on T1-weighted image (WI) with the preservation of epidural fat and
      a hypointensity on T2WI. A decompressive surgery was scheduled to perform within
      2 days after the cervical MRI scan because of a previous anticoagulation therapy,
      but the patient refused it. Finally, 9 days after the onset, surgical
      decompression and removal of hematoma were performed. Three months
      postoperatively, the patient had fully recovered demonstrating fine hand movement
      and good ability to walk up and down the stairs. CONCLUSIONS: Our study indicates
      that it is essential to perform cervical MRI when a patient does not show an
      improvement in the neurologic deficit and has a negative brain MRI after
      acupuncture. In addition, blind acupuncture if not correctly practiced may be
      harmful to the cervical structures.

PMID- 24094992
TI  - Biomechanical evaluation of a metal-on-metal cervical intervertebral disc
      prosthesis.
AB  - BACKGROUND CONTEXT: In vitro nondestructive flexibility testing of the CerviCore
      total disc replacement (TDR) was performed. It was hypothesized that TDR would
      not significantly alter biomechanics relative to intact, whereas rigid fixation
      would cause significant changes. PURPOSE: To assess the ability of a cervical
      metal-on-metal saddle-shaped TDR to replicate normal biomechanics in vitro. STUDY
      DESIGN: Human cadaveric flexibility experiment. METHODS: Nine human cadaveric C3
      T1 specimens were tested intact, after TDR and after anterior plating. Flexion,
      extension, lateral bending, and axial rotation were induced by pure moments;
      flexion-extension was then repeated using a simplified muscle force model with 70
      N follower load. Optical markers measured three-dimensional intervertebral
      motion, and eight points of laminar surface strain were recorded near the left
      and right C5-C6 facet joints. Biomechanical parameters studied included range of
      motion (ROM), lax zone (LZ), angular coupling pattern, sagittal instantaneous
      axis of rotation (IAR), and facet loads normal to the facet joint plane. Mean
      values of parameters were compared statistically using repeated measures analysis
      of variance and Holm-Sidak tests. RESULTS: Total disc replacement caused
      significant reduction in ROM during extension (p=.004) and significant reduction
      in LZ during lateral bending (p=.01). However, plating significantly reduced both
      ROM and LZ during flexion, extension, and lateral bending (p<.006). Sagittal IAR
      shifted relative to intact by 3.6 mm after TDR (p>.05) and 6.5 mm after plating
      (p>.05). Coupled axial rotation/degree lateral bending was 99% of intact after
      TDR but 76% of intact after plating (p=.15). Coupled lateral bending/degree axial
      rotation was 95% of intact after TDR but 85% of intact after plating (p=.43).
      Neither construct altered facet loads from intact. CONCLUSIONS: With regard to
      ROM, LZ, IAR, and coupling, deviations from intact biomechanics were less
      substantial after TDR than after plating. Facet load alterations were minimal
      with either construct. Our results show that this particular TDR permits ROM and
      maintains some measures of kinematics in a cadaver model.

PMID- 24094993
TI  - Spectroscopic investigation on interaction and sonodynamic damage of Riboflavin
      to DNA under ultrasonic irradiation by using Methylene Blue as fluorescent probe.
AB  - In this paper, the Riboflavin (RF) as a sonosensitizer and Methylene Blue (MB) as
      a fluorescent probe were used to study the interaction and sonodynamic damage to
      Deoxyribonucleic Acid (DNA) by fluorescence and UV-vis spectroscopy. The results
      showed that the RF could efficiently bind to DNA in aqueous solution and exchange
      with the MB through competing reaction. And then, under ultrasonic irradiation,
      the RF could obviously damage the DNA. In addition, the influencing factors such
      as ultrasonic irradiation time and RF concentration on the sonodynamic damage to
      DNA were also considered. The experimental results showed that the sonodynamic
      damage degree increase with the increase of ultrasonic irradiation time and RF
      concentration. Perhaps, this paper may offer some important subjects for
      broadening the application of RF in sonodynamic therapy (SDT) technologies for
      tumor treatment. 

PMID- 24094994
TI  - Preface to special issue on computational spectroscopy.

PMID- 24094995
TI  - Isolated glyoxylic acid-water 1:1 complexes in low temperature argon matrices.
AB  - The 1:1 hydrogen bonded complexes between glyoxylic acid (GA) and water are
      studied in low temperature argon matrices. Four different complex structures were
      found in deposited matrices. The lowest energy conformer (T1) of GA was found to
      form complex, where the water molecule was attached to the opposite side of the
      intramolecular hydrogen bond in the molecule (T1B). Interestingly, this complex
      was estimated to be+8.0 kJ mol(-1) higher in energy than the most stable
      structure (T1A), where the water is inserted into the internal hydrogen bond, and
      also found in solid argon but in smaller abundance. For the second-lowest energy
      conformer of GA (T2), the two lowest-energy complex structures were identified,
      with the most stable complex structure (T2A) also being the most abundant in the
      matrices. The difference between experiment and computational energetic order of
      the two complex structures of the same GA conformer is explained by contributions
      of deformation energy upon complexation and the effect of the environment. The
      computed BSSE-corrected interaction energies are for the two most stable
      complexes of the two GA conformers for T1A and T2A -42.11 and -45.03 kJ mol(-1),
      respectively, at the CCSD(T)/aug-cc-pVTZ//B3LYP/aug-cc-pVTZ level of theory.

PMID- 24094996
TI  - Dissipation of excess photosynthetic energy contributes to salinity tolerance: a
      comparative study of salt-tolerant Ricinus communis and salt-sensitive Jatropha
      curcas.
AB  - The relationships between salt tolerance and photosynthetic mechanisms of excess
      energy dissipation were assessed using two species that exhibit contrasting
      responses to salinity, Ricinus communis (tolerant) and Jatropha curcas
      (sensitive). The salt tolerance of R. communis was indicated by unchanged
      electrolyte leakage (cellular integrity) and dry weight in leaves, whereas these
      parameters were greatly affected in J. curcas. The leaf Na+ content was similar
      in both species. Photosynthesis was intensely decreased in both species, but the
      reduction was more pronounced in J. curcas. In this species biochemical
      limitations in photosynthesis were more prominent, as indicated by increased C(i)
      values and decreased Rubisco activity. Salinity decreased both the V(cmax) (in
      vivo Rubisco activity) and J(max) (maximum electron transport rate) more
      significantly in J. curcas. The higher tolerance in R. communis was positively
      associated with higher photorespiratory activity, nitrate assimilation and higher
      cyclic electron flow. The high activity of these alternative electron sinks in R.
      communis was closely associated with a more efficient photoprotection mechanism.
      In conclusion, salt tolerance in R. communis, compared with J. curcas, is related
      to higher electron partitioning from the photosynthetic electron transport chain
      to alternative sinks.

PMID- 24094997
TI  - Assessment of female sexual function among women with pelvic organ prolapse or
      urinary incontinence via an Arabic validated short-form sexual questionnaire.
AB  - OBJECTIVE: To assess female sexual function among women with pelvic organ
      prolapse or urinary incontinence via an Arabic, validated, short-form sexual
      questionnaire (PISQ-12). METHODS: The present study was conducted among women
      attending Suez Canal University Hospital, Ismailia, Egypt, between September 2009
      and August 2011. In the pilot study, 42 women completed the final version of the
      Arabic PISQ-12 at recruitment and then 2 weeks later, and the data were compared
      to evaluate reliability and internal consistency. The formal comparative study
      included 154 premenopausal sexually active women: 80 control women, and 74 women
      with some degree of pelvic prolapse with or without stress incontinence. All
      participants had a vaginal examination and completed the questionnaire. The main
      outcome measures were the mean questionnaire scores within its 3 domains
      (behavioral, physical, and partner-related). RESULTS: The test-retest reliability
      and internal consistency of the Arabic PISQ-12 were excellent. Validity was
      approved by an expert panel. The case group had a significantly lower mean total
      questionnaire score (31.07 +/- 4.2 vs 34.7 +/- 6.2; P<0.05) but a higher partner
      related score (9.0 +/- 2.4 vs 8.4 +/- 2.5; P<0.05). CONCLUSION: The Arabic
      version of PISQ-12 was shown to be an effective and objective method of
      evaluating sexual function among patients with pelvic organ prolapse.

PMID- 24094998
TI  - Impact of a program of physiotherapy and health education on the outcome of
      obstetric fistula surgery.
AB  - OBJECTIVE: Surgery is the only successful treatment for most obstetric fistulae.
      The present study measured the impact of a structured program of pre- and
      postoperative physiotherapy and health education on the outcome of surgery for
      obstetric fistula. METHODS: We compared the postoperative outcomes of 2
      consecutive groups of women with obstetric fistulae who were recruited and
      followed-up by 2 local nongovernmental organizations at a hospital in Tanguieta,
      Benin. The first group of women (n=99) had fistula repair using standardized
      techniques. The second group (n=112) had a standardized surgical approach plus a
      structured program of pre- and postoperative health education and physiotherapy.
      RESULTS: The program had a significant positive impact on recovery in general and
      on urinary incontinence in particular. After physiotherapy, the odds of recovery
      were 2.72 times greater for women in the physiotherapy group than for control
      patients, and the probability of postoperative stress incontinence was
      considerably higher for patients in the control group than for those in the
      physiotherapy group (P<0.001). CONCLUSION: A structured program of health
      education and physiotherapy by experienced nurses and physiotherapists improves
      the likelihood of a successful outcome after surgical repair of obstetric
      fistula.

PMID- 24094999
TI  - Testing a theory of organizational culture, climate and youth outcomes in child
      welfare systems: a United States national study.
AB  - Theories of organizational culture and climate (OCC) applied to child welfare
      systems hypothesize that strategic dimensions of organizational culture influence
      organizational climate and that OCC explains system variance in youth outcomes.
      This study provides the first structural test of the direct and indirect effects
      of culture and climate on youth outcomes in a national sample of child welfare
      systems and isolates specific culture and climate dimensions most associated with
      youth outcomes. The study applies multilevel path analysis (ML-PA) to a U.S.
      nationwide sample of 2,380 youth in 73 child welfare systems participating in the
      second National Survey of Child and Adolescent Well-being. Youths were selected
      in a national, two-stage, stratified random sample design. Youths' psychosocial
      functioning was assessed by caregivers' responses to the Child Behavior Checklist
      at intake and at 18-month follow-up. OCC was assessed by front-line caseworkers'
      (N=1,740) aggregated responses to the Organizational Social Context measure.
      Comparison of the a priori and subsequent trimmed models confirmed a reduced
      model that excluded rigid organizational culture and explained 70% of the system
      variance in youth outcomes. Controlling for youth- and system-level covariates,
      systems with more proficient and less resistant organizational cultures exhibited
      more functional, more engaged, and less stressful climates. Systems with more
      proficient cultures and more engaged, more functional, and more stressful
      climates exhibited superior youth outcomes. Findings suggest child welfare
      administrators can support service effectiveness with interventions that improve
      specific dimensions of culture and climate. 

PMID- 24095000
TI  - Cannabis for therapeutic purposes: patient characteristics, access, and reasons
      for use.
AB  - BACKGROUND: The authorized and unauthorized use of cannabis for therapeutic
      purposes (CTP) has increased dramatically in recent years, and physicians have
      called for further research to better clarify the parameters of effective and
      appropriate use. We report findings from a large cross-sectional study of the use
      of CTP in Canada and compare use across medical conditions and across authorized
      and unauthorized users. METHODS: We examined cannabis use history, medical
      conditions and symptoms, patterns of current use of CTP, modes of access and
      perceived effectiveness among 628 self-selected Canadians consumers of CTP.
      Participants were recruited from medical cannabis dispensaries and from
      organizations that assist users of CTP. RESULTS: Patients reported using cannabis
      to treat multiple symptoms, with sleep, pain, and anxiety being the most common.
      Cannabis was perceived to provide effective symptoms relief across medical
      conditions. Patterns of use were also consistent across medical conditions.
      Notable differences were observed with regard to modes of access. CONCLUSION:
      Across medical conditions respondents reported using cannabis to effectively
      address diverse symptoms. Results indicate a substantial disconnect between the
      therapeutic use of cannabis and research on the risks and benefits of such use;
      particularly with regard to the anxiolytic and sedative use of cannabis.
      Authorized and unauthorized users exhibited few meaningful differences with
      regard to medical conditions and patterns of use, but faced substantial
      differences regarding access.

PMID- 24095002
TI  - Referral for substance abuse treatment and depression improvement among patients
      with co-occurring disorders seeking behavioral health services in primary care.
AB  - This study examined the relationship between substance treatment referrals and
      depression improvement among 2,373 participants with concurrent substance use and
      depressive disorders enrolled in an integrated behavioral health program. Three
      groups of substance treatment referral status were identified: accessed treatment
      (n=780), declined treatment (n=315), and no referral for treatment (n=1278). The
      primary outcome is improvement in depressive symptoms (PHQ-9<10 or >=50%
      reduction). Using propensity score adjustments, patients accessing substance
      treatment were significantly more likely to achieve depression improvement than
      those who declined receiving treatment services (hazard ratio (HR)=1.82, 95%
      confidence interval (CI): 1.50-2.20, p<0.001) and those without a referral for
      treatment (HR=1.13, 95% CI: 1.03-1.25, p=0.014). Each 1 week delay in initiating
      a referral was associated with a decreased likelihood of depression improvement
      (HR=0.97, 95% CI: 0.96-0.98, p<0.001). Study findings highlight the need of
      enhancing early treatment contact for co-occurring substance use disorders in
      primary care.

PMID- 24095003
TI  - Autism and EMF? Plausibility of a pathophysiological link - Part I.
AB  - Although autism spectrum conditions (ASCs) are defined behaviorally, they also
      involve multileveled disturbances of underlying biology that find striking
      parallels in the physiological impacts of electromagnetic frequency and
      radiofrequency exposures (EMF/RFR). Part I of this paper will review the critical
      contributions pathophysiology may make to the etiology, pathogenesis and ongoing
      generation of core features of ASCs. We will review pathophysiological damage to
      core cellular processes that are associated both with ASCs and with biological
      effects of EMF/RFR exposures that contribute to chronically disrupted
      homeostasis. Many studies of people with ASCs have identified oxidative stress
      and evidence of free radical damage, cellular stress proteins, and deficiencies
      of antioxidants such as glutathione. Elevated intracellular calcium in ASCs may
      be due to genetics or may be downstream of inflammation or environmental
      exposures. Cell membrane lipids may be peroxidized, mitochondria may be
      dysfunctional, and various kinds of immune system disturbances are common. Brain
      oxidative stress and inflammation as well as measures consistent with blood-brain
      barrier and brain perfusion compromise have been documented. Part II of this
      paper will review how behaviors in ASCs may emerge from alterations of
      electrophysiological oscillatory synchronization, how EMF/RFR could contribute to
      these by de-tuning the organism, and policy implications of these
      vulnerabilities. Changes in brain and autonomic nervous system
      electrophysiological function and sensory processing predominate, seizures are
      common, and sleep disruption is close to universal. All of these phenomena also
      occur with EMF/RFR exposure that can add to system overload ('allostatic load')
      in ASCs by increasing risk, and worsening challenging biological problems and
      symptoms; conversely, reducing exposure might ameliorate symptoms of ASCs by
      reducing obstruction of physiological repair. Various vital but vulnerable
      mechanisms such as calcium channels may be disrupted by environmental agents,
      various genes associated with autism or the interaction of both. With dramatic
      increases in reported ASCs that are coincident in time with the deployment of
      wireless technologies, we need aggressive investigation of potential ASC -
      EMF/RFR links. The evidence is sufficient to warrant new public exposure
      standards benchmarked to low-intensity (non-thermal) exposure levels now known to
      be biologically disruptive, and strong, interim precautionary practices are
      advocated. 

PMID- 24095001
TI  - A short history of hemogenic endothelium.
AB  - Definitive hematopoietic cells are generated de novo during ontogeny from a
      specialized subset of endothelium, the so-called hemogenic endothelium. In this
      review we give a brief overview of the identification of hemogenic endothelium,
      explore its links with the HSC lineage, and summarize recent insights into the
      nature of hemogenic endothelium and the microenvironmental and intrinsic
      regulators contributing to its transition into blood. Ultimately, a better
      understanding of the processes controlling the transition of endothelium into
      blood will advance the generation and expansion of hematopoietic stem cells for
      therapeutic purposes. 

PMID- 24095004
TI  - Mandibular fractures treated with small plates and screws reduce treatment cost.
AB  - PURPOSE: The efficacy of treating mandibular fractures with open reduction and
      internal fixation (ORIF) using small titanium plates and monocortical screws is
      well established. The purpose of this study was to determine whether the use of
      semirigid (small) titanium plates results in lower treatment charges. PATIENTS
      AND METHODS: Consecutive patients with mandibular fractures were randomly
      allocated to ORIF with small or large titanium plates. The primary predictor
      variable for this secondary subset analysis was plate size. The primary outcome
      variable was total treatment charges. Other outcomes included length of stay
      (LOS), operating room charges, hardware charges, LOS charge, and charges related
      to the treatment of complications. RESULTS: A total of 127 consecutive patients
      were enrolled in the study. Fifty-two patients completed the required 6-week
      follow-up and had data available for analysis. Adjusted total treatment charges
      suggested a significant difference, with a mean total treatment charge of $15,308
      in the semirigid group and a mean total treatment charge of $16,557 in the rigid
      group (P = .04). Total treatment charges were 8% higher in the rigid group
      compared with the semirigid group. CONCLUSIONS: The findings of this study
      suggest that the overall charges associated with treating mandibular fractures
      with ORIF are significantly lower when semirigid plates are used.

PMID- 24095005
TI  - Comparison of local anesthetic efficacy of tramadol hydrochloride (with
      adrenaline) versus plain tramadol hydrochloride in the extraction of upper molar
      teeth.
AB  - PURPOSE: To evaluate the efficacy of local anesthesia using tramadol
      hydrochloride (HCl) with versus without adrenaline in the extraction of upper
      molar teeth. PATIENTS AND METHODS: This was a double-blinded study that included
      100 patients who required extraction of 1 upper molar by the conventional method
      and were allocated randomly into 1 of 2 groups: in group A (n = 50), each patient
      received an initial dose of drug A (tramadol HCl 50 mg and adrenalin 0.0225 mg
      diluted to 1.8 mL by distilled water); in group B (n = 50), each patient received
      an initial dose of drug B (tramadol HCl 50 mg diluted to 1.8 mL by distilled
      water). Degree of pain during tooth extraction, duration of surgery, and total
      number of cartridges used were recorded intraoperatively. Postoperatively,
      patients were instructed to record any adverse effects, such as nausea or
      vomiting, on the first day of the operation. RESULTS: There were significant
      differences in the number of cartridges used and the degree of intraoperative
      pain. However, there was no significant difference in duration of surgery or side
      effects. CONCLUSIONS: The results of this study suggest that tramadol HCl in
      combination with adrenaline can be used as an alternative local anesthetic in
      oral and maxillofacial surgery when, for some unusual reason, a patient cannot
      receive a conventional local anesthetic.

PMID- 24095006
TI  - Navigation-guided lateral gap arthroplasty as the treatment of temporomandibular
      joint ankylosis.
AB  - PURPOSE: This article presents a novel method of navigation-guided lateral gap
      arthroplasty (LGA) in the treatment of temporomandibular joint ankylosis (TMJA).
      MATERIALS AND METHODS: Six patients with unilateral TMJA from 2007 through 2011
      were included in this study. Presurgical planning was performed to determine the
      amount and extent of ankylosed bone to be resected using the simulation platform.
      Minimum follow-up was 6 months. Patients were monitored for complications and
      signs of recurrence. Maximum mouth opening (MO) was measured and compared intra-
      and postoperatively. RESULTS: Preoperative planning was performed at the STN or
      Accu-Navi workstation. The amount and extent of ankylosed bone to be resected was
      determined. All 6 LGAs were completed successfully using real-time instrument-
      and pointer-based navigation. Measurements performed intraoperatively showed that
      the mean for maximum MO was about 35 to 40 mm and remained the same
      postoperatively. Follow-up evaluation showed remarkable improvement in function
      and esthetics, with no signs of recurrence. CONCLUSION: Navigation-guided LGA can
      be regarded a viable option for performing this delicate and complicated surgical
      procedure.

PMID- 24095007
TI  - Extracting value from oral and maxillofacial surgery.

PMID- 24095008
TI  - Takotsubo cardiomyopathy precipitated by maxillofacial surgery and general
      anesthesia: a case report and review of literature.
AB  - PURPOSE: Takotsubo cardiomyopathy (TCM) is a syndrome characterized by a
      transient episode of heart failure. The specific etiology of this condition is
      widely speculated. The purpose of this case report and literature review was to
      investigate the incidence of TCM with regard to general anesthesia, especially
      those cases involving operative procedures within the realm of oral and
      maxillofacial surgery. It is intended that the present case serve as a guide for
      fellow surgeons to identify and manage this syndrome. MATERIALS AND METHODS: The
      present case was explained and a review of the literature was performed. PubMed
      was used to search for articles involving surgical procedures under general
      anesthesia, including oral and maxillofacial surgery. RESULTS: It was determined
      that TCM rarely occurs in conjunction with surgical procedures under general
      anesthesia, especially those of the head and neck region. CONCLUSIONS: TCM is an
      uncommon medical condition with significant morbidity and mortality when managed
      incorrectly. The occurrence of this syndrome in relation to oral and
      maxillofacial procedures is also rare, although it is imperative that surgeons be
      able to recognize and treat this condition appropriately.

PMID- 24095009
TI  - Measuring upper airway volume: accuracy and reliability of Dolphin 3D software
      compared to manual segmentation in craniosynostosis patients.
AB  - PURPOSE: To test the accuracy and reliability of Dolphin 3-dimensional (3D)
      software airway analysis compared with manual segmentation in patients who
      underwent a Le Fort III osteotomy. MATERIALS AND METHODS: Computed tomographic
      scans of 20 patients with syndromic craniosynostosis at Sophia's Children's
      Hospital (Rotterdam, The Netherlands) were used for airway volume measurements
      using Dolphin 3D. The same scans had been used for measurement using a manual
      segmentation method. The results of this previous study were reported in 2010.
      The manual segmentation measuring result was used as a gold standard. The airway
      was subdivided into the oropharynx and the nasal passage. A linear mixed effects
      statistical model was applied. RESULTS: Dolphin 3D measurements differed from
      manual segmentation by 9 to 43%, depending on the observer, the time at which the
      measured scan was acquired (pre- or postoperative), and the airway compartment
      being measured. The highest accuracy for Dolphin 3D was found for measurements
      from postoperative scans of the nasal passage. CONCLUSION: The airway analysis
      tool of Dolphin 3D is not accurate or reliable enough to use in a Le Fort III
      osteotomy evaluation. When scanning properties are conditioned and measurements
      are standardized, accuracy and reliability may increase.

PMID- 24095010
TI  - Synthesis and pharmacological evaluation of carboxycoumarins as a new antitumor
      treatment targeting lactate transport in cancer cells.
AB  - Under hypoxia, cancer cells consume glucose and release lactate at a high rate.
      Lactate was recently documented to be recaptured by oxygenated cancer cells to
      fuel the TCA cycle and thereby to support tumor growth. Monocarboxylate
      transporters (MCT) are the main lactate carriers and therefore represent
      potential therapeutic targets to limit cancer progression. In this study, we have
      developed and implemented a stepwise in vitro screening procedure on human cancer
      cells to identify new potent MCT inhibitors. Various 7-substituted
      carboxycoumarins and quinolinone derivatives were synthesized and
      pharmacologically evaluated. Most active compounds were obtained using a
      palladium-catalyzed Buchwald-Hartwig type coupling reaction, which proved to be a
      quick and efficient method to obtain aminocarboxycoumarin derivatives. Inhibition
      of lactate flux revealed that the most active compound 19 (IC50 11 nM) was three
      log orders more active than the CHC reference compound. Comparison with warfarin,
      a conventional anticoagulant coumarin, further showed that compound 19 did not
      influence the prothrombin time which, together with a good in vitro ADME profile,
      supports the potential of this new family of compounds to act as anticancer drugs
      through inhibition of lactate flux.

PMID- 24095011
TI  - Aminopropyl carbazole analogues as potent enhancers of neurogenesis.
AB  - Neural stem cells are multipotent and self-renewing cells that can differentiate
      into new neurons and hold great promise for treating various neurological
      disorders including multiple sclerosis, Parkinson's disease, and Alzheimer's
      disease. Small molecules that can trigger neurogenesis and neuroprotection are
      particularly useful not only because of their therapeutic implications but also
      because they can provide an invaluable tool to study the mechanisms of
      neurogenesis. In this report, we have developed and screened 25 aminopropyl
      carbazole derivatives that can enhance neurogenesis of cultured neural stem
      cells. Among these analogues, compound 9 demonstrated an excellent proneurogenic
      and neuroprotective activity with no apparent toxicity. We believe that compound
      9 can serve as an excellent lead to develop various analogues and to study the
      underlying mechanisms of neurogenesis. 

PMID- 24095012
TI  - Pheophytinization kinetics of chlorophyll c under weakly acidic conditions:
      effects of acrylic acid residue at the 17-position.
AB  - Pheophytinization of chlorophyll (Chl) c1, which was isolated from the diatom
      Chaetoceros gracilis, was kinetically analyzed under weakly acidic conditions,
      and was compared with that of protochlorophyllide (PChlide) a and chlorophyllide
      (Chlide) a. Chl c1 possessing a trans-acrylic acid residue at the 17-position
      exhibited slower pheophytinization kinetics than PChlide a and Chlide a, both of
      which possessed a propionic acid residue at the same position. The difference in
      pheophytinization properties between Chl c1 and (P)Chlide a was ascribable to the
      electronegativity of the 17-substituent in Chl c1 larger than that of (P)Chlide a
      due to the C17(1)-C17(2) double bond with the conjugated 17(2)-carboxy group in
      Chl c1. Demetalation kinetics of PChlide a was slower than that of Chlide a,
      which originated from the effect of the pi-macrocyclic structures. 

PMID- 24095013
TI  - Synthesis, antiproliferative and mitochondrial impairment activities of bis-alkyl
      amino transplatinum complexes.
AB  - A convenient synthetic route and the characterization of complexes trans
      [PtCl2(L)(PPh3)] (L=Et2NH (2), (PhCH2)2NH (3), (HOCH2CH2)2NH) (4) are reported.
      The antiproliferative activity was evaluated on three human tumor cell lines. The
      investigation on the mechanism of action highlighted for the most active complex
      4 the capacity to affect mitochondrial functions. In particular, both the
      induction of the mitochondrial permeability transition phenomenon and an
      aspecific membrane damage occurred, depending on concentration. 

PMID- 24095014
TI  - N-Alkyl dien- and trienamides from the roots of Otanthus maritimus with binding
      affinity for opioid and cannabinoid receptors.
AB  - Two new thienylheptatrienamides (1, 5) and one new neo-lignan (12), together with
      thirteen known compounds (2, 3, 4, 6-11, 13-16) were isolated from the roots of
      Otanthus maritimus. The structures of the new compounds were elucidated on the
      basis of extensive 1D and 2D NMR experiments as well as high resolution mass
      spectrometry. All the isolated amides (1-10), the known pontica epoxide (11) and
      the new neo-lignan (12) were evaluated for their binding affinity to the CB1 and
      CB2 as well as to the MU and delta opioid receptors. Some alkylamides showed
      moderately high binding affinity for CB2 receptors and 1-[(2E,4E,8Z)
      tetradecatrienoyl]piperidine (10) resulted the most active one with a Ki value of
      160 nM. As far as we know, this is the first example of a tertiary alkylamide
      that binds CB2 receptors with significant potency. Compounds that showed the
      highest affinity for cannabinoid receptors (6-8, 10) were much less potent
      against opioid receptors. Primary structure-activity relationship is discussed.
      Docking experiments were carried out with the aim to understand the key
      interactions of the most active compounds with CB2 receptor.

PMID- 24095015
TI  - Perindopril and ramipril phosphonate analogues as a new class of angiotensin
      converting enzyme inhibitors.
AB  - A series of phosphonate analogues related to perindopril and ramipril were
      prepared and tested to estimate their ability to inhibit angiotensin converting
      enzyme. These new synthesized compounds were active ACE inhibitors with a
      promising activity. 

PMID- 24095016
TI  - Development of novel ferulic acid derivatives as potent histone deacetylase
      inhibitors.
AB  - Histone deacetylase inhibitors (HDACIs) offer a promising strategy for cancer
      therapy. The discovery of potent ferulic acid-based HDACIs with hydroxamic acid
      or 2-aminobenzamide group as zinc binding group was reported. The halogeno
      acetanilide was introduced as novel surface recognition moiety (SRM). The
      majority of title compounds displayed potent HDAC inhibitory activity. In
      particular, FA6 and FA16 exhibited significant enzymatic inhibitory activities,
      with IC50 values of 3.94 and 2.82 MUM, respectively. Furthermore, these compounds
      showed moderate antiproliferative activity against a panel of human cancer cells.
      FA17 displayed promising profile as an antitumor candidate. The results indicated
      that these ferulic acid derivatives could serve as promising lead compounds for
      further optimization.

PMID- 24095017
TI  - The enzyme 3-hydroxykynurenine transaminase as potential target for 1,2,4
      oxadiazoles with larvicide activity against the dengue vector Aedes aegypti.
AB  - The mosquito Aedes aegypti is the vector agent responsible for the transmission
      of yellow fever and dengue fever viruses to over 80 million people in tropical
      and subtropical regions of the world. Exhaustive efforts have lead to a vaccine
      candidate with only 30% effectiveness against the dengue virus and failure to
      protect patients against the serotype 2. Hence, vector control remains the most
      viable route to dengue fever control programs. We have synthesized a class of
      1,2,4-oxadiazole derivatives whose most biologically active compounds exhibit
      potent activity against Aedes aegypti larvae (ca. of 15 ppm) and low toxicity in
      mammals. Exposure to these larvicides results in larvae pigmentation in a manner
      correlated with the LC50 measurements. Structural comparisons of the 1,2,4
      oxadiazole nucleus against known inhibitors of insect enzymes allowed the
      identification of 3-hydroxykynurenine transaminase as a potential target for
      these synthetic larvicides. Molecular docking calculations indicate that 1,2,4
      oxadiazole compounds can bind to 3-hydroxykynurenine transaminase with similar
      conformation and binding energies as its crystallographic inhibitor 4-(2
      aminophenyl)-4-oxobutanoic acid.

PMID- 24095018
TI  - The discovery and optimization of novel dual inhibitors of topoisomerase II and
      histone deacetylase.
AB  - A novel class of podophyllotoxin derivatives have been designed and synthesized
      based on the synergistic antitumor effects of topoisomerase II and histone
      deacetylase inhibitors. Their inhibitory activities towards histone deacetylases
      and Topo II and their cytotoxicities in cancer cell lines were evaluated. The
      aromatic capping group connection, linker length and zinc-binding group were
      systematically varied and preliminary conclusions regarding structure-activity
      relationships are discussed. Among all of the synthesized hybrid compounds,
      compound 24 d showed the most potent HDAC inhibitory activity at a low nanomolar
      level and exhibited powerful antiproliferative activity towards HCT116 colon
      carcinoma cells at a low micromolar level. Further exploration of this series led
      to the discovery of potent dual inhibitor 32, which exhibited the strongest in
      vitro cytotoxic activity.

PMID- 24095019
TI  - Synthesis and evaluation of the cell cycle arrest and CT DNA interaction
      properties of 4beta-amino-4'-O-demethyl-4-deoxypodophyllotoxins.
AB  - A series of 4beta-amino-4'-O-demethyl-4-deoxypodophyllotoxin derivatives were
      synthesized, and their cytotoxicities against several human cancer cell lines,
      including HepG2, A549, HeLa and HCT-8 cells, evaluated. Some of these compounds
      exhibited higher levels of cytotoxicity than the anticancer drug etoposide. 4beta
      N-(4-Nitrophenyl piperazinyl)-4'-O-demethyl-4-deoxypodophyllotoxin (11) was found
      to be the most potent synthesized compound in the current study, and induced cell
      cycle arrest in the G2/M phase in HeLa cells, which was accompanied by apoptosis.
      Furthermore, this compound activated the expression of cdc2, cyclin B1, p53 and
      caspase-3 in HeLa cells, leading to changes in the conformation of calf thymus
      DNA from the B-form to a more compact C-form. 

PMID- 24095021
TI  - Allogenous bone with collagen for repair of deep osteochondral defects.
AB  - BACKGROUND: A scaffold for treatment of deep osteochondral defects should be
      stable, integrate well, and provide a surface for chondrocytes. To meet these
      demands, a biphasic scaffold of allogenous sterilized bone with a collagen
      surface was developed. Integration was tested in the sheep model. MATERIAL AND
      METHODS: Cartilage chips were taken from the nonweight-bearing area of the left
      knee of 12 sheep and cultured. After 4 wk a second procedure followed and defects
      of 9.4-mm diameter at the weight-bearing area of the medial femoral condyle of
      the right knee were created. The sterilized scaffold was inserted and the
      cultured autologous chondrocytes were dripped onto the surface. After 6 wk, 3 mo,
      and 6 mo the animals were sacrificed; the explanted femoral condyles were
      evaluated macroscopically and using histologic, immunohistochemical, and
      electronmicroscopic methods. RESULTS: After 6 wk the level of the surface was
      well preserved, after 3 mo parts of the scaffold were sintered but after 6 mo the
      surface was continuous. Full integration of the allogenous bone could be observed
      after 6 mo. The surface of the scaffold after 6 wk consisted of bone, but after 3
      mo some chondrocytes and after 6 mo a continuous chondral layer could be
      detected. CONCLUSIONS: The biphasic scaffold of allogenous bone and collagen
      proved to be stable and sufficiently integrated in the short- and midterm
      interval. Whether the chondrocytes on the surface had been derived from implanted
      chondrocytes or the scaffold with its surface was sufficiently chondroconductive
      must be answered in further investigations.

PMID- 24095020
TI  - Benzochalcones bearing pyrazoline moieties show anti-colorectal cancer activities
      and selective inhibitory effects on aurora kinases.
AB  - Colorectal cancer is the third and fourth leading cause of cancer in males and
      females, respectively. Flavonoids, including chalcones, are secondary metabolites
      in plants that exhibit diverse biological activities, including antibacterial,
      antimalarial, and antitumor activities. In order to find potent and novel
      chemotherapy drugs for colorectal cancer, a series of benzochalcone derivatives,
      in which an alpha,beta-unsaturated carbonyl group was replaced with a pyrazoline,
      was designed and synthesized. A clonogenic survival assay was performed with each
      derivative to evaluate antitumor activity. 1-(5-(2,4-Dimethoxyphenyl)-4,5-dihydro
      1H-pyrazol-3-yl)naphthalen-2-ol (derivative 7) had the most potent inhibitory
      effect on the long-term clonogenicity of HCT116 human colorectal cancer cells
      (IC50=2.4 MUM). The results of Western blot and flow cytometric analyses
      suggested that derivative 7 could inhibit the proliferation of colorectal cancer
      cells through inhibition of cell cycle progression and induction of apoptosis. To
      elucidate its molecular mechanism, in vitro kinase binding assays were carried
      out, which demonstrated that derivative 7 inhibited aurora kinases A and B
      selectively. The binding modes between the compound and aurora kinases were
      interpreted using in silico docking experiments to explain the selective
      inhibitory effects on aurora kinases A and B. These findings will facilitate the
      design of potent novel benzochalcones as anticancer agents.

PMID- 24095022
TI  - Pure NOTES transvaginal appendectomy with gasless laparoscopy.
AB  - BACKGROUND: The vagina is the most widely used approach to natural orifice
      transluminal endoscopic surgery. However, a gas leak can significantly affect
      transvaginal operations during pneumoperitoneum laparoscopy. We tried to
      establish the proper technique for transvaginal appendectomy under gasless
      laparoscopy. MATERIALS AND METHODS: Five patients with chronic appendicitis were
      selected to receive gasless laparoscopic transvaginal appendectomy with
      concurrent vaginal hysterectomy. An abdominal wall-lifting device was applied
      after removal of the uterus, and the appendix was removed transvaginally.
      Clinical data such as operative duration, bleeding volume, morbidity, and
      hospital stay duration were analyzed. RESULTS: All procedures were performed
      successfully, without intraoperative or major postoperative complications. The
      appendectomy portion of the procedure took approximately 20-30 minutes, with
      minimal blood loss. All patients were discharged, scar-free, 3 d after surgery.
      CONCLUSIONS: Transvaginal appendectomy with gasless laparoscopy after vaginal
      hysterectomy appears to be a feasible and safe modification of established
      techniques, with acceptable outcomes.

PMID- 24095023
TI  - Triple-layer duct-to-mucosa pancreaticojejunostomy with resection of jejunal
      serosa decreased pancreatic fistula after pancreaticoduodenectomy.
AB  - BACKGROUND: Pancreatic fistula (PF) is one of the most common complications after
      pancreaticoduodenectomy (PD). We described a new method of pancreaticojejunostomy
      (PJ) developed by combining triple-layer duct-to-mucosa PJ with resection of
      jejunal serosa, which was named as modified layer-to-layer PJ (MLLPJ). The aim of
      the present study was to observe whether the new technique would effectively
      reduce the PF rate in comparison with two-layer duct-to-mucosa PJ (TLPJ).
      METHODS: Data on 184 consecutive patients who underwent the two methods of PJ
      after standard PD between January 1, 2010 and January 31, 2013 were collected
      retrospectively from a prospective database. The primary endpoint was the PF
      rate. The risk factors of PF were investigated by using univariate and
      multivariate analyses. RESULTS: A total of 88 patients received TLPJ and 96
      underwent MLLPJ. Rate of PF for the entire cohort was 8.2%. There were 11
      fistulas (12.5%) in the TLPJ group and four fistulas (4.2%) in the MLLPJ group (P
      = 0.039). Body mass index, pancreatic texture, pancreatic duct diameter, and
      methods of PJ anastomosis had significant effects on the formation of PF on
      univariate analysis. Multivariate analysis showed that pancreatic duct diameter
      <=3 mm and TLPJ were the significant risk factors of PF. CONCLUSIONS: MLLPJ
      effectively reduces the PF rate after PD in comparison with TLPJ. Results confirm
      increased PF rates in patients with pancreatic duct diameter <=3 mm compared with
      pancreatic duct diameter >3 mm.

PMID- 24095024
TI  - Adipose-derived stem cells enhance tissue regeneration of gastrotomy closure.
AB  - BACKGROUND: The aim of this study was to examine whether transplantation of
      adipose-derived stem cells (ADSCs) improves healing of a gastrotomy closure in
      rats. In digestive surgery, anastomotic leakage is a serious postoperative
      complication and anastomotic stenosis may reduce quality of life. Recent studies
      have suggested that ADSCs play material roles in intestinal healing, acceleration
      of angiogenesis, and reduction of fibrosis, and treatment with ADSCs may improve
      healing. MATERIALS AND METHODS: ADSCs were isolated from intra-abdominal white
      adipose tissue of 40 male Wistar rats (weight 300 g) in four groups (n = 10
      each). Gastrotomy closures were prepared surgically in all rats. Controls were
      treated with phosphate-buffered saline injection and sacrificed 7 d (group 1) or
      28 d (group 3) after the surgery. Other animals were treated with locally
      autotransplanted ADSCs (labeled by CM-DiI) and sacrificed 7 d (group 2) or 28 d
      (group 4) after the surgery. Histopathologic features were evaluated in the four
      groups. RESULTS: Injection of ADSCs significantly enhanced angiogenesis and
      collagen deposition after 7 d, indicating improved healing of the gastrotomy
      closure. In contrast, ADSC transplantation significantly reduced collagen
      deposition after 28 d. The bursting pressure was higher in the transplant groups
      after 7 d. CONCLUSIONS: ADSCs enhance tissue regeneration in gastrotomy closures
      by accelerating angiogenesis and fibrosis in the early healing period. In the
      late period, ADSCs prevent excessive fibrosis and assist in regeneration of
      tissues that closely resemble the native structure. These results suggest that
      therapy with transplanted ADSCs might improve postoperative complications in
      digestive surgery.

PMID- 24095026
TI  - In vitro comparative evaluation of recombinant growth factors for tissue
      engineering of bladder in patients with neurogenic bladder.
AB  - BACKGROUND: To compare the effects of various recombinant growth factors on
      bladder regeneration and angiogenesis for tissue engineering of bladder in
      patients with neurogenic bladder through in vitro cellular biological methods.
      MATERIALS AND METHODS: Human bladder smooth muscle cells (HBSMCs) and human
      bladder urothelial cells (HBUCs) were cultured from patients with neurogenic
      bladder and used for comparative evaluations of various growth factors. Human
      umbilical vein endothelial cells (HUVECs) were also used. Eight potential growth
      factors, platelet-derived growth factor BB (PDGF-BB), platelet-derived growth
      factor CC (PDGF-CC), basic fibroblast growth factor (bFGF), vascular endothelial
      growth factor (VEGF), epidermal growth factor (EGF), insulin-like growth factor 1
      (IGF-1), hepatocyte growth factor (HGF), and transforming growth factor beta 1
      (TGF-beta1), were selected and their effects on the proliferation, migration, and
      wound healing of HBSMCs, HBUCs, and HUVECs were compared. RESULTS: PDGF-BB, PDGF
      CC, bFGF, VEGF, IGF-1, or HGF enhanced the proliferation, migration, and wound
      healing of HBSMCs, whereas TGF-beta1 inhibited their proliferation.
      Proliferation, migration, and wound healing of HBUCs and HUVECs were enhanced by
      bFGF, VEGF, EGF, IGF-1, or HGF, whereas inhibited by TGF-beta1. PDGF-BB failed to
      enhance cell activity of HUVECs, whereas PDGF-CC could enhance their migration
      and wound healing. PDGF-BB, EGF, and VEGF were the most potent factors for
      stimulating the activities of HBSMCs, HBUCs, and HUVECs, respectively.
      CONCLUSIONS: Our findings suggest the potential use of a combination of PDGF-BB,
      EGF, and VEGF for bladder regeneration and angiogenesis. The synergetic effects
      of the three growth factors on cell activities in a three-dimensional scaffold
      and an animal model with neurogenic bladder need to be further evaluated.

PMID- 24095025
TI  - Lymph node involvement in immunohistochemistry-based molecular classifications of
      breast cancer.
AB  - BACKGROUND: Prognosis and treatment options differ for each molecular subtype of
      breast cancer, but risk of regional lymph node (LN) metastasis for each subtype
      has not been well studied. Since LN status is the most important predictor for
      prognosis, the aim of this study is to investigate the propensity for LN
      metastasis in each of the five breast cancer molecular subtypes. METHODS: Under
      an institutional review board-approved protocol, we retrospectively reviewed the
      charts of all pathologically confirmed breast cancer cases from January 2004 to
      June 2012. Five subtypes were defined as luminal A (hormone receptor positive, Ki
      67 low), luminal B (hormone receptor positive, Ki-67 high), luminal human
      epidermal growth factor receptor 2 (HER2), HER2-enriched (hormone receptor
      negative), and triple negative (TN). RESULTS: A total of 375 patients with
      complete data were classified by subtype: 95 (25.3%) luminal A, 120 (32%) luminal
      B, 69 (18.4%) luminal HER2, 26 (6.9%) HER2-enriched, and 65 (17.3%) TN. On
      univariate analysis, age (<50), higher tumor grade, HER2+ status, tumor size, and
      molecular subtype were significant for LN positivity. Molecular subtype
      correlated strongly with tumor size (chi(2); P = 0.0004); therefore,
      multivariable logistic regression did not identify molecular subtype as an
      independent variable to predict LN positivity. CONCLUSIONS: Luminal A tumors have
      the lowest risk of LN metastasis, whereas luminal HER2 subtype has the highest
      risk of LN metastasis. Immunohistochemical-based molecular classification can be
      readily performed and knowledge of the factors that affect LN status may help
      with treatment decisions.

PMID- 24095027
TI  - Development and evaluation of NS1 specific monoclonal antibody based antigen
      capture ELISA and its implications in clinical diagnosis of West Nile virus
      infection.
AB  - BACKGROUND: West Nile virus (WNV) is a neurotropic flavivirus that causes viral
      encephalitis. Recent epidemics of WNV around the world have been associated with
      significant rates of mortality and morbidity in humans. The early confirmatory
      diagnosis of WNV infection is important for timely clinical management and
      epidemiological control in areas where multiple flaviviruses are endemic.
      OBJECTIVE: The aim of this study is to develop an monoclonal antibody based
      antigen capture ELISA for early confirmatory diagnosis of WNV infection with high
      degree of specificity and sensitivity having no cross reactivity with any of the
      closely related members of other circulating viruses. STUDY DESIGN: The gene
      coding for the NS1 protein of WNV was cloned and expressed in pET-28a expression
      vector. Purified recombinant protein was then utilized for generation of mice
      monoclonal antibody (Mab) and hyper immune sera (HIS) in rabbit. The sandwich
      ELISA was developed using the rabbit HIS and mice Mab as capture and detector
      antibody respectively and the results were compared with real time RT-PCR by
      evaluating 105 suspected clinical samples. RESULTS: The comparative evaluation of
      the sandwich ELISA with real time RT-PCR revealed 97% concordance with
      sensitivity and specificity of 90% and 98% respectively. CONCLUSION: The WN NS1
      antigen was detectable in the blood from the first day up to day 9 after the
      onset of symptoms. The higher sensitivity and specificity of this monoclonal
      Antibody based sandwich ELISA makes it useful for early diagnosis of WN infection
      in endemic areas during outbreaks.

PMID- 24095028
TI  - Genotype impact on HCV RNA levels determined with the VERSANT HCV RNA 1.0 assay
      (kPCR).
AB  - BACKGROUND: Accurate quantitation of hepatitis C virus (HCV) RNA is mandatory for
      the management of anti-HCV therapy. OBJECTIVES: The genotype-dependent
      performance of the new commercially available VERSANT HCV RNA 1.0 Assay (kPCR)
      and the COBAS AmpliPrep/COBAS TaqMan HCV Quantitative Test, version 2.0 was
      investigated. STUDY DESIGN: The molecular assays for quantitation of HCV RNA were
      performed according to the manufacturer's package insert instructions. HCV
      genotypes/subtypes/isolates, and mutations in the 5'NCR were detected by direct
      sequencing. RESULTS: When members of a worldwide HCV performance panel including
      HCV subtypes 1a, 1b, 2a, 3b, and 4a were tested with the Siemens assay and the
      results were compared with those obtained by the Roche assay, the mean log10 unit
      differences for members containing HCV subtypes 1a, 1b, 3b, and 4a were found to
      be within +/-0.5 log(10) units. For the panel member containing HCV subtype 2a,
      the HCV RNA concentration was found to be >0.5 log(10) units lower with the
      Siemens assay. When clinical samples were tested, the HCV RNA concentration of
      all samples containing HCV subtype 2a were found to be >0.5 log(10) units lower
      with the Siemens assay while that of certain HCV subtype 3a and 4a isolates were
      found to be >1.0 log(10) units lower. CONCLUSION: The VERSANT HCV RNA 1.0 Assay
      substantially underestimates HCV RNA concentrations in HCV subtype 2a samples and
      in HCV subtype 3a and 4a samples containing certain isolates. This may be caused
      by mismatches with the target sequences due to the primer and/or probe design.

PMID- 24095029
TI  - Utility of HTLV proviral load quantification in diagnosis of HTLV-1-associated
      myelopathy requires international standardization.

PMID- 24095031
TI  - Cancer, chemotherapy and cognition.

PMID- 24095030
TI  - Relation of serum magnesium levels and postdischarge outcomes in patients
      hospitalized for heart failure (from the EVEREST Trial).
AB  - Serum magnesium levels may be impacted by neurohormonal activation, renal
      function, and diuretics. The clinical profile and prognostic significance of
      serum magnesium level concentration in patients hospitalized for heart failure
      (HF) with reduced ejection fraction is unclear. In this retrospective analysis of
      the placebo group of the Efficacy of Vasopressin Antagonism in Heart Failure
      Outcome Study with Tolvaptan trial, we evaluated 1,982 patients hospitalized for
      worsening HF with ejection fractions <=40%. Baseline magnesium levels were
      measured within 48 hours of admission and analyzed as a continuous variable and
      in quartiles. The primary end points of all-cause mortality (ACM) and
      cardiovascular mortality or HF rehospitalization were analyzed using Cox
      regression models. Mean baseline magnesium level was 2.1 +/- 0.3 mg/dl. Compared
      with the lowest quartile, patients in the highest magnesium level quartile were
      more likely to be older, men, have lower heart rates and blood pressures, have
      ischemic HF origin, and have higher creatinine and natriuretic peptide levels
      (all p <0.003). During a median follow-up of 9.9 months, every 1-mg/dl increase
      in magnesium level was associated with higher ACM (hazard ratio [HR] 1.77; 95%
      confidence interval [CI] 1.35 to 2.32; p <0.001) and the composite end point (HR
      1.44; 95% CI 1.15 to 1.81; p = 0.002). However, after adjustment for known
      baseline covariates, serum magnesium level was no longer an independent predictor
      of either ACM (HR 0.94, 95% CI 0.69 to 1.28; p = 0.7) or the composite end point
      (HR 1.01, 95% CI 0.79 to 1.30; p = 0.9). In conclusion, despite theoretical
      concerns, baseline magnesium level was not independently associated with worse
      outcomes in this cohort. Further research is needed to understand the importance
      of serum magnesium levels in specific HF patient populations. 

PMID- 24095032
TI  - Pathogenesis of virus-associated human cancers: Epstein-Barr virus and hepatitis
      B virus as two examples.
AB  - Virus-associated human cancers may exhibit two characteristic histopathologic
      features: (1) the inflammation-rich background as observed in Epstein-Barr virus
      associated Hodgkin lymphoma (HL) and nasopharyngeal carcinoma (NPC); and (2) the
      characteristic nuclear morphology such as the Reed-Sternberg cells in HL.
      Besides, the hepatocytes of chronic hepatitis B virus (HBV) infection frequently
      exhibit characteristic ground glass hepatocytes, a phenomenon associated with
      endoplasmic reticulum stress response induced by the overloaded or malfolded HBV
      surface antigens. In this review, we explore specifically the pathogenesis of
      Epstein-Barr virus-associated HL and NPC, and HBV-associated hepatocellular
      carcinoma based on the observed histopathologic features. We propose that the
      retention of viral proteins induces inflammation, endoplasmic reticulum stress,
      and genomic instability in HL, NPC, and hepatocellular carcinoma, whereby the
      viral oncoproteins may play additional transactivational roles to induce host
      genes for transformation, invasion, and metastasis. Therapeutic implications
      based on the pathogenesis of virus-associated cancers are discussed. 

PMID- 24095033
TI  - Surface modification of halloysite nanotubes with dopamine for enzyme
      immobilization.
AB  - Halloysite nanotubes (HNTs) have been proposed as a potential support to
      immobilize enzymes. Improving enzyme loading on HNTs is critical to their
      practical applications. Herein, we reported a simple method on the preparation of
      high-enzyme-loading support by modification with dopamine on the surface of HNTs.
      The modified HNTs were characterized by transmission electron microscopy, Fourier
      transform infrared spectroscopy, and X-ray photoelectron spectroscopy analyses.
      The results showed that dopamine could self-polymerize to adhere to the surface
      of HNTs and form a thin active coating. While the prepared hybrid nanotubes were
      used to immobilize enzyme of laccase, they exhibited high loading ability of
      168.8 mg/g support, which was greatly higher than that on the pristine HNTs (11.6
      mg/g support). The immobilized laccase could retain more than 90% initial
      activity after 30 days of storage and the free laccase only 32%. The immobilized
      laccase could also maintain more than 90% initial activity after five repeated
      uses. In addition, the immobilized laccase exhibited a rapid degradation rate and
      high degradation efficiency for removal of phenol compounds. These advantages
      indicated that the new hybrid material can be used as a low-cost and effective
      support to immobilize enzymes. 

PMID- 24095034
TI  - [Postoperative visual loss: A case report of a hysterical conversion after a
      spine surgery].

PMID- 24095036
TI  - Characterisation of FOGs in grease trap waste from the processing of chickens in
      Thailand.
AB  - Industrial firms that kill and process chickens generate wastewater that contains
      fat, oil, and grease (FOG). The FOGs are located in the fatty waste that is
      collected by floatation in grease traps. Chemical and physical characterisation
      of FOGs would provide useful information that would help in the development of
      methods designed to decrease the extent of pollution caused by disposal of the
      waste and to utilise commercially some of its lipid constituents. Employing these
      methods would enhance the profitability and competitive potential of these
      commercial organisations. Samples of grease trap waste from 14 firms in central
      Thailand have been examined. Due to the very different schemes of waste
      management employed by these firms, the physical appearance of their fatty wastes
      showed considerable variation. The chemical and physical properties of the FOGs
      present in these wastes showed considerable variation also. Large amounts of free
      fatty acids (10-70% as oleic acid) were detected in most of the 14 wastes and
      palmitic, cis-9-oleic, cis,cis-9,12-linoleic, stearic, and palmitoleic acids were
      the predominant species of free and esterified acids. Most of the FOGs were solid
      at temperatures below 40  degrees C. Many of them contained traces of heavy
      metals (Cu and Pb) and some contained traces of the pesticides dimethoate and
      cypermethrin. The content of these potentially hazardous substances would have to
      be considered very carefully before discarding the fatty wastes and during the
      development of methods designed to isolate their potentially profitable lipid
      constituents.

PMID- 24095035
TI  - [Preoperative cardiac-risk assessment for non-cardiac surgery: The French RICARDO
      survey].
AB  - OBJECTIVES: Professional practice evaluation of anaesthesiologist for high
      cardiac-risk patient cares in non-cardiac surgery, and assess disparities between
      results and recommendations. MATERIALS AND METHODS: Since June to September 2011,
      a self-questionnaire was sent to 5000 anesthesiologist. They were considered to
      be representative of national anesthesiology practitioner. Different items
      investigated concerned: demography, preoperative cardiac-risk assessment,
      modalities of specialized cardiologic advice, per- and postoperative care, and
      finally knowledge of current recommendations. RESULTS: We collected 1255
      questionnaire, that is to say 25% of answers. Men were 73%, 38% were employed by
      public hospital; 70% worked in a shared operating theatre with a general
      activity. With regards to preoperative assessment, 85% of anaesthetists referred
      high cardiac-risk patient to a cardiologist. In only 16% of answer, Lee's score
      appeared in anaesthesia file to assess perioperative cardiac-risk. Only 61%
      considered the six necessary items to optimal estimate of cardiac-risk. On the
      other hand, 91% measured routinely the exercise capacities by interrogation. The
      most frequently doing exam (49% of anaesthetist) was an electrocardiogram in
      elderly patient. In 96% of case, beta-blockers were given in premedication if
      they were usually thought. Clopidogrel was stopped by 62% of anesthetist before
      surgery. In this case, 38% used another medication to take over from this one.
      Only 7% considered revascularization in coronary patient who were effectively
      treated. POISE study was know by 40% of practitioner, and 18% estimated that they
      have changed their practice. Preoperatively, 21% organized multidisciplinary
      approach for high-risk patient. During surgery, 63% monitored the ST-segment. In
      postoperative period for cardiac-risk patient, only 11% prescribed systematically
      an ECG, a troponin dosage, a postoperative monitoring of ST-segment, a
      cardiologic advice. In case of moderate troponin elevation, they were 70% to
      realize at least an ECG and/or an echocardiography. CONCLUSION: This study
      highlights some difference between current recommendation concerning assessment
      of cardiac-risk patient in non-cardiac surgery and daily practice of anesthetist,
      justifying regular update of this one.

PMID- 24095037
TI  - Percutaneous wire rescue during radial sheath insertion.
AB  - Radial artery catheterization is a common procedure performed in the cardiac
      catheterization laboratory. Transradial accesssing is becoming an increasingly
      widespread choice because of its lower complications compared with the
      transfemoral approach. Although complications related to this procedure are well
      established, troubles associated with the guide wire are rare. We present the
      first reported case of a percutaneous rescue of a wire during radial sheath
      insertion using the balloon entrapment technique to retrieve it without surgery. 

PMID- 24095038
TI  - Influenza outbreaks management in a French psychiatric hospital from 2004 to
      2012.
AB  - OBJECTIVE: Influenza epidemics can have consequences in terms of morbidity and
      mortality for the patients. This work assesses influenza outbreaks in order to
      validate and optimize alert and control measures in a psychiatric hospital.
      METHOD: The prospective monitoring of influenza episodes was conducted for 8
      years in 19 units of a mental health hospital. Rapid influenza diagnostic tests
      were used. The study of the episodes with confirmed influenza cases was carried
      out. RESULTS: Influenza monitoring and alert were essential with information and
      laboratory-confirmed cases. Influenza was common with a total of 20 episodes for
      the studied period. A maximum of 25% (5/20) of the units were affected in 2008
      2009. Rapid influenza diagnostic tests allowed a quick identification with an
      average time of 1.5 days. Mainly, control measures limited the spread of the
      influenza virus in units with patient not at high risk of complications. On the
      other hand, antiviral curative treatment and chemoprophylaxis are essential in
      units with patients at high risk of complications. CONCLUSION: In a psychiatric
      hospital, influenza management has to take into account the exposed patient's
      risks for influenza complications and to adapt the strategy according to the
      risks identified.

PMID- 24095039
TI  - Outcomes of endovascular lower extremity interventions depend more on indication
      than physician specialty.
AB  - OBJECTIVE: Outcomes of endovascular lower extremity interventions (eLEIs) have
      been recently linked to provider specialty; however, the indication for
      intervention was not examined. We sought to compare outcomes between specialties
      performing eLEI for different indications, in a recent statewide inpatient
      discharge dataset. METHODS: The Florida hospital discharge data from 2005 to 2009
      were reviewed for patients with LEI during hospitalization. We assigned provider
      specialty as interventional radiology (IR), interventional cardiology (IC), or
      vascular surgery (VS) based on provider-associated procedures. Clinical
      indication was claudication or critical limb ischemia (CLI). We limited our
      analysis to patients without concomitant open surgery during hospitalization. We
      compared mortality, length of stay (LOS), major use of intensive care unit (ICU),
      discharge disposition, and total charges between specialties with regression
      models, both unadjusted and adjusted for demographic and clinical
      characteristics. RESULTS: A total of 15,398 patients (47% with CLI) had an eLEI.
      Clinical indication was significantly associated with provider type (P < .001)
      and outcomes. VS and IR were more likely than IC to treat CLI patients (VS 59%,
      IR 65%, IC 26%; P < .001). IC performed the majority of procedures on claudicants
      (VS 30%, IC 57%, IR 13%; P < .001), while VS performed the majority of procedures
      on CLI patients (VS 50%, IC 23%, IR 27%; P < .001). Adjusted analyses
      demonstrated no difference in mortality rates between the three specialties (odds
      ratio [OR] VS: reference, IR: 1.24, IC: 0.79; P = NS for both). However, compared
      with VS, IR-treated patients were less likely to be discharged home (OR, 0.74; P
      < .001), LOS was longer (beta, 1.16 days; P < .001), major ICU use was more
      common (OR, 1.49; P < .001), and total charges were higher (beta, $341; P =
      .001). CLI predicted poorer results for all outcomes: death (OR, 4.19; P < .001),
      discharge home (OR, 0.50; P < .001), increased LOS (beta, 3.26 days; P < .001),
      major ICU use (OR, 1.95; P < .001), and total charges (beta, $18,730; P < .001).
      CONCLUSIONS: The majority of eLEI done by VS are for CLI, whereas the majority of
      patients treated by IC are claudicants. Although provider specialty does
      correlate with several clinical results, the clinical indication for eLEI is a
      stronger predictor of adverse outcomes. Future analyses of eLEI should adjust for
      clinical indication.

PMID- 24095040
TI  - Oxidative stress precedes skeletal muscle mitochondrial dysfunction during
      experimental aortic cross-clamping but is not associated with early lung, heart,
      brain, liver, or kidney mitochondrial impairment.
AB  - OBJECTIVE: Lower limb ischemia-reperfusion results in skeletal muscle
      mitochondrial alterations, production of reactive oxygen species (ROS), and
      remote organ impairments that are largely involved in patient prognosis. However,
      whether ischemia without reperfusion increases ROS production and precedes
      mitochondrial alteration and whether mitochondrial dysfunction occurs early in
      remote organs is unknown. This study determined muscle mitochondrial function and
      ROS production after ischemia alone, or followed by two periods of reperfusion,
      and investigated heart, lung, liver, kidney, and brain mitochondrial functions
      after lower limb ischemia-reperfusion. METHODS: Wistar rats were randomized into
      four groups: sham (aortic exposure but no ischemia, n = 9), I3 (ischemia alone
      induced by aortic cross-clamping for 3 hours, n = 9), I3R10' and I3R2 (aortic
      cross-clamping, followed by reperfusion for 10 minutes [n = 8] or 2 hours [n =
      9]). Blood lactate, alanine aminotransferase, aspartate aminotransferase, and
      creatinine were measured. Mitochondrial respiratory chain complexes I, II, III,
      and IV activities and mitochondrial coupling (acceptor control ratio) were
      analyzed using a Clark oxygen electrode in skeletal muscle, lung, heart, brain,
      liver, and kidney. ROS production was determined using dihydroethidium staining
      in muscle, heart, liver, and kidney. Inflammation was also investigated in remote
      organs (heart, liver, and kidney) using monocyte-macrophage-2 antibody staining.
      RESULTS: Lactate level increased after ischemia in all groups. In muscle, ROS
      increased significantly after ischemia alone (+324% +/- 66%; P = .038),
      normalized after 10 minutes of reperfusion, and increased again at 2 hours of
      reperfusion (+349.2 +/- 67%; P = .024). Interestingly, mitochondrial function was
      unaffected by ischemia alone or followed by 10 minutes of reperfusion, but
      maximal mitochondrial oxidative capacity (6.10 +/- 0.51 vs. 4.24 +/- 0.36
      MUmol/min/g, -30%; P < .05) and mitochondrial coupling decreased after 2 hours of
      reperfusion (1.93 +/- 0.17 vs. 1.33 +/- 0.07, -45%; P < .01), in sham and I3R2
      rats, respectively. Despite increased serum aspartate aminotransferase (*13; P <
      .0001), alanine aminotransferase (*6; P = .0019), and creatinine (*3; P = .0004),
      remote organs did not show mitochondrial alteration, inflammation, or ROS
      production enhancement after 2 hours of reperfusion. CONCLUSIONS: Oxidative
      stress precedes skeletal muscle mitochondrial dysfunction during lower limb
      ischemia. Such a kinetic explains the efficacy of ischemic preconditioning and
      supports that therapy should be conducted even during ongoing ischemia,
      suggesting that ischemic preconditioning might be a successful approach.

PMID- 24095041
TI  - Thrombus volume is similar in patients with ruptured and intact abdominal aortic
      aneurysms.
AB  - OBJECTIVE: Most abdominal aortic aneurysms (AAAs) contain intraluminal thrombus
      (ILT), which has been demonstrated to contain proteolytic enzymes and
      proinflammatory cytokines implicated in AAA progression and rupture. In animal
      models, anticoagulants have been shown to limit AAA progression. Whether ILT
      plays a role in AAA rupture is unknown. The aim of this study was to compare the
      volume of ILT in patients with ruptured and intact AAAs. METHODS: We matched by
      maximum axial diameter alone, on a 1:2 basis, 28 patients with ruptured AAAs and
      56 patients with intact AAAs. Total infrarenal aortic volume and ILT volume were
      measured from computed tomography angiograms using a previously validated and
      reproducible semiautomated workstation protocol. Clinical risk factors were also
      recorded. The Mann-Whitney U test was used to compare ILT volumes between
      patients with ruptured and intact AAAs. RESULTS: Median (interquartile range
      [IQR]) maximum AAA diameter (84.0 [77.5-93.9] mm vs 82.6 [77.1-93.3] mm; P =
      .769) and median (IQR) total AAA volume (372.8 [277.4-486.1] cm(3) vs 358.4
      [289.1-563.4] cm(3); P = .977) were similar in patients with ruptured and intact
      AAAs. Median (IQR) AAA ILT volume was similar in patients with ruptured (152.7
      [84.8-252.4] cm(3)) and intact (180.1 [89.9-254.8] cm(3); P = .414) AAAs.
      CONCLUSIONS: This study suggests that ILT volume is not different in ruptured and
      intact AAAs.

PMID- 24095044
TI  - [Intra-articular osteoid osteoma in the left elbow].
AB  - Intra-articular osteoid osteoma (OO) is a rare and difficult diagnosis. We report
      the case of an 11-year-old boy who presented with inflammatory monoarticular
      arthritis in the left elbow. This monoarthritis was resistant to all types of
      treatment. He had an OO, diagnosed late because the first symptoms developed
      subsequent to the ablation of a wart in the same elbow and were suggestive of
      arthritis. 

PMID- 24095043
TI  - Local wall thickness in finite element models improves prediction of abdominal
      aortic aneurysm growth.
AB  - OBJECTIVE: Growing evidence suggests that peak wall stress (PWS) derived from
      finite element analysis (FEA) of abdominal aortic aneurysms (AAAs) predicts
      clinical outcomes better than diameter alone. Prior models assume uniform wall
      thickness (UWT). We hypothesize that the inclusion of locally variable wall
      thickness (VWT) into FEA of AAAs will improve its ability to predict clinical
      outcomes. METHODS: Patients with AAAs (n = 26) undergoing radiologic surveillance
      were identified. Custom MATLAB algorithms generated UWT and VWT aortic geometries
      from computed tomography angiography images, which were subsequently loaded with
      systolic blood pressure using FEA. PWS and aneurysm expansion (as a proxy for
      rupture risk and the need for repair) were examined. RESULTS: The average
      radiologic follow-up time was 22.0 +/- 13.6 months and the average aneurysm
      expansion rate was 2.8 +/- 1.7 mm/y. PWS in VWT models significantly differed
      from PWS in UWT models (238 +/- 68 vs 212 +/- 73 kPa; P = .025). In our sample,
      initial aortic diameter was not found to be correlated with aneurysm expansion (r
      = 0.26; P = .19). A stronger correlation was found between aneurysm expansion and
      PWS derived from VWT models compared with PWS from UWT models (r = 0.86 vs r =
      0.58; P = .032 by Fisher r to Z transformation). CONCLUSIONS: The inclusion of
      locally VWT significantly improved the correlation between PWS and aneurysm
      expansion. Aortic wall thickness should be incorporated into future FEA models to
      accurately predict clinical outcomes.

PMID- 24095046
TI  - Xylose induces the phyllosphere yeast Pseudozyma antarctica to produce a cutinase
      like enzyme which efficiently degrades biodegradable plastics.
AB  - There is a need to speed up the degradation of used agricultural mulch films that
      are made of biodegradable plastics (BPs) in the field. Treating them with BP
      degrading enzymes could be a solution to this problem. A cutinase-like enzyme of
      yeast Pseudozyma antarctica (PaE) has wide specificity of BPs degradation, but
      needs to be produced efficiently. Here we report that the production of PaE by P.
      antarctica can be increased by using xylose as carbon source. BP-degradation
      activity was analyzed using a polybutylene succinate-co-adipate (PBSA) emulsion
      as the substrate. Strain P. antarctica GB-4(1)W was found to be the best PaE
      producer among the tested strains. Using a 5-L jar fermentor with xylose fed
      batch cultivation, high PaE productivity could be maintained and about 21 U/ml of
      PaE was obtained in 120 h. This amount was 100 times higher than the amount that
      we obtained previously (0.21 U/ml by flask cultivation using glycerol as carbon
      source). Under repeated xylose fed-batch cultivation with 24 h intervals, the
      maximum PaE production rate (0.34 U/ml/h) was maintained and the highest PaE
      productivity (28,000 U/2 L/d) was repeatedly obtained for 7 intervals. The
      activity of filtered jar-culture (crude PaE) was stable over 12 weeks at 4
      degrees C. Commercially available BP mulch films (20 MUm thickness, cut into 1-cm
      squares) were completely degraded by submerging them in crude PaE (2 U/ml) at 30
      degrees C in 24 h. These results indicated that concentrated PaE can rapidly
      degrade the strength of BP mulch films in the field so that they do not interfere
      with plowing.

PMID- 24095048
TI  - Titanium determination by multisyringe flow injection analysis system and a
      liquid waveguide capillary cell in solid and liquid environmental samples.
AB  - A multisyringe flow injection analysis system using a liquid waveguide capillary
      cell (MSFIA-LWCC) has been used for the spectrophotometric determination of
      titanium (Ti) in marine environmental samples. Samples were previous digested
      using potassium peroxodisulfate (K2S2O8). The method showed to be linear over a
      range up to 1 MUM with a detection limit of 9.2 nM. The analysis consumes little
      reagent (250 MUL) and sample (600 MUL). It had an adequate accuracy with high
      repeatability (RSD of 1.8%) for all marine samples. The proposed method was used
      to evaluate the concentration of Ti in natural samples collected in the coastal
      area of the Majorca Island (Western Mediterranean Sea). We report average
      concentrations of Ti in coastal surface microlayer of 510.7 +/- 267.2 nM, in
      surface sediments of 2.72 +/- 1.84 MUmol/g, and in rhizomes and leaves of
      Posidonia oceanica of 310 +/- 295 nmol/g and 157 +/- 132 nmol/g, respectively.

PMID- 24095047
TI  - Alert thresholds for monitoring environmental variables: a new approach applied
      to seagrass beds diversity in New Caledonia.
AB  - Monitoring ecological variables is mandatory to detect abnormal changes in
      ecosystems. When the studied variables exceed predefined alert thresholds,
      management actions may be required. In the past, alert thresholds have been
      typically defined by expert judgments and descriptive statistics. Recently,
      approaches based on statistical power were also used. In New Caledonia, seagrass
      monitoring is a priority given their vulnerability to natural and anthropic
      disturbances. To define a suitable monitoring strategy and alert thresholds, we
      compared a Percentile Based Approach (PBA) and a sensitivity analysis of power
      (SAP). Both methods defined statistically relevant alert thresholds, but the SAP
      approach was more robust to spatial and temporal variability of seagrass cover.
      Moreover, this method characterized the sensitivity of threshold values to
      sampling efforts, a useful knowledge for managers. 

PMID- 24095042
TI  - Vein graft failure.
AB  - After the creation of an autogenous lower extremity bypass graft, the vein must
      undergo a series of dynamic structural changes to stabilize the arterial
      hemodynamic forces. These changes, which are commonly referred to as remodeling,
      include an inflammatory response, the development of a neointima, matrix
      turnover, and cellular proliferation and apoptosis. The sum total of these
      processes results in dramatic alterations in the physical and biomechanical
      attributes of the arterialized vein. The most clinically obvious and easily
      measured of these is lumen remodeling of the graft. However, although somewhat
      less precise, wall thickness, matrix composition, and endothelial changes can be
      measured in vivo within the healing vein graft. Recent translational work has
      demonstrated the clinical relevance of remodeling as it relates to vein graft
      patency and the systemic factors influencing it. By correlating histologic and
      molecular changes in the vein, insights into potential therapeutic strategies to
      prevent bypass failure and areas for future investigation are explored.

PMID- 24095049
TI  - Silicon alleviates cadmium toxicity in Avicennia marina (Forsk.) Vierh. seedlings
      in relation to root anatomy and radial oxygen loss.
AB  - The effects of Si on growth, the anatomy of the roots, radial oxygen loss (ROL)
      and Fe/Mn plaque on the root surface were investigated in Avicennia marina
      (Forsk.) Vierh. seedlings under Cd stress. Si prompted the growth of seedlings
      and reduced the Cd concentration in the root, stem and leaf of A. marina. Si
      prompted the development of the apoplastic barrier in the roots, which may be
      related to the reduction of Cd uptake. The higher amount of ROL and Mn plaque on
      the root surface due to Si were also related to the promotion of Cd tolerance in
      A. marina seedlings. Therefore, it is concluded that the alteration of the
      anatomy of the roots, the increase of ROL and Mn plaque of A. marina seedlings
      play an important role in alleviation of Cd toxicity due to Si. 

PMID- 24095051
TI  - The importance of developing military cultural competence.

PMID- 24095050
TI  - Abundance of class 1-3 integrons in South Carolina estuarine ecosystems under
      high and low levels of anthropogenic influence.
AB  - The impact of human activity on the spread of antibiotic resistant bacteria
      throughout coastal estuarine ecosystems is not well characterized. It has been
      suggested that laterally transferred genetic agents, such as integrons, play a
      role in the spread of resistant bacteria throughout ecosystems. This study
      compares the distribution of three integron classes throughout a coastal
      estuarine ecosystem. To determine integron distribution patterns, DNA was
      extracted from sediment and water collected at seven sites throughout two
      estuaries with different levels of anthropogenic input and integrons analyzed
      using quantitative PCR. The data show that while all three integron classes are
      present, the relative abundance is different, with class 2 integrons
      significantly elevated in areas of high anthropogenic input and class 1 integrons
      elevated in areas of low input. Our results provide a foundation for using
      integron gene distribution as a biomarker of urban impact on antibiotic
      resistance gene flow and ecosystem health. 

PMID- 24095052
TI  - Military experience talks.

PMID- 24095053
TI  - Ergosterol peroxide from Cordyceps cicadae ameliorates TGF-beta1-induced
      activation of kidney fibroblasts.
AB  - Chronic kidney disease is a growing public health problem with an urgent need for
      new pharmacological agents. Ergosterol peroxide (EP) is the major sterol produced
      by Cordyceps cicadae Shing (C. cicadae), a widely used traditional Chinese
      medicine. C. cicadae has been used to treat many kinds of diseases and has a
      potential benefit on renoprotection. This study aimed to investigate the anti
      fibrotic effects of EP as well as the underlying mechanisms. A normal rat kidney
      fibroblast cell line (NRK-49F) was stimulated to undergo fibroblast activation by
      transforming growth factor-beta1 (TGF-beta1) and EP treatment was applied to
      explore its potential anti-fibrotic effects. Cell proliferation was investigated
      using MTT analysis. Fibrosis-associated protein expression was analyzed using
      immunohistochemistry and/or Western blotting. EP treatment attenuated TGF-beta1
      induced renal fibroblast proliferation, expression of cytoskeleton protein and
      CTGF, as well as ECM production. Additionally, EP blocked TGF-beta1-stimulated
      phosphorylation of ERK1/2, p38 and JNK pathway. Moreover, the TGF-beta1-induced
      expression of fibronectin was attenuated by either inhibition of MAPKs or by EP
      treatment. In conclusion, our findings demonstrate that EP is able to suppress
      TGF-beta1-induced fibroblasts activation in NRK-49F. This new information
      provides a line of theoretical evidence supporting the use of C. cicadae in the
      intervention of kidney disease and suggests that EP has the potential to be
      developed as a therapeutic agent to prevent renal fibrosis. 

PMID- 24095054
TI  - Rituximab: Recommendations of the French Vasculitis Study Group (FVSG) for
      induction and maintenance treatments of adult, antineutrophil cytoplasm antibody
      associated necrotizing vasculitides.
AB  - Increasing rituximab prescription for ANCA-associated necrotizing vasculitides
      justifies the publication of recommendations for clinicians. Rituximab is
      approved in the United States to induce and maintain remission. In Europe,
      rituximab was recently approved for remission induction. However, governmental
      agencies' approvals cannot replace clinical practice guidelines. Herein, the
      French Vasculitis Study Group Recommendations Committee, comprised of physicians
      with extensive experience in the treatment of vasculitides, presents its
      consensus guidelines based on literature analysis, the results of prospective
      therapeutic trials and personal experience. 

PMID- 24095056
TI  - Does the use of tranexamic acid improve trauma mortality?

PMID- 24095055
TI  - [Vitamin D: several potential effects on health].

PMID- 24095057
TI  - Neck posture and muscle activity are different when upside down: a human
      volunteer study.
AB  - Rollover crashes are dynamic and complex events in which head impacts with the
      roof can cause catastrophic neck injuries. Ex vivo and computational models are
      valuable in understanding, and ultimately preventing, these injuries. Although
      neck posture and muscle activity influence the resulting injury, there is
      currently no in vivo data describing these parameters immediately prior to a head
      first impact. The specific objectives of this study were to determine the in vivo
      neck vertebral alignment and muscle activation levels when upside down, a
      condition that occurs during a rollover. Eleven human subjects (6F, 5M) were
      tested while seated upright and inverted in a custom-built apparatus. Vertebral
      alignment was measured using fluoroscopy and muscle activity was recorded using
      surface and indwelling electrodes in eight superficial and deep neck muscles. In
      vivo vertebral alignment and muscle activation levels differed between the
      upright and inverted conditions. When inverted and relaxed, the neck was more
      lordotic, C1 was aligned posterior to C7, the Frankfort plane was extended, and
      the activity of six muscles increased compared to upright and relaxed. When
      inverted subjects were asked to look forward to eliminate head extension, flexor
      muscle activity increased, C7 was more flexed, and C1 was aligned anterior to C7
      versus upright and relaxed. Combined with the large inter-subject variability
      observed, these findings indicate that cadaveric or computational models designed
      to study injuries and prevention devices while inverted need to consider a
      variety of postures and muscle conditions to be relevant to the in vivo
      situation. 

PMID- 24095058
TI  - Crystal structure of human Seryl-tRNA synthetase and Ser-SA complex reveals a
      molecular lever specific to higher eukaryotes.
AB  - Seryl-tRNA synthetase (SerRS), an essential enzyme for translation, also
      regulates vascular development. This "gain-of-function" has been linked to the
      UNE-S domain added to vertebrate SerRS during evolution. However, the
      significance of two insertions also specific to higher eukaryotic SerRS remains
      elusive. Here, we determined the crystal structure of human SerRS in complex with
      Ser-SA, an aminoacylation reaction intermediate analog, at 2.9 A resolution.
      Despite a 70 A distance, binding of Ser-SA in the catalytic domain dramatically
      leverages the position of Insertion I in the tRNA binding domain. Importantly,
      this leverage is specific to higher eukaryotes and not seen in bacterial,
      archaeal, and lower eukaryotic SerRSs. Deletion of Insertion I does not affect
      tRNA binding but instead reduce the catalytic efficiency of the synthetase. Thus,
      a long-range conformational and functional communication specific to higher
      eukaryotes is found in human SerRS, possibly to coordinate translation with
      vasculogenesis. 

PMID- 24095059
TI  - Structural basis for eliciting a cytotoxic effect in HER2-overexpressing cancer
      cells via binding to the extracellular domain of HER2.
AB  - Human epidermal growth factor receptor-2 (HER2) is a receptor tyrosine kinase
      directly linked to the growth of malignancies from various origins and a
      validated target for monoclonal antibodies and kinase inhibitors. Utilizing a new
      approach with designed ankyrin repeat proteins (DARPins) as alternative binders,
      we show that binding of two DARPins connected by a short linker, one targeting
      extracellular subdomain I and the other subdomain IV, causes much stronger
      cytotoxic effects on the HER2-addicted breast cancer cell line BT474, surpassing
      the therapeutic antibody trastuzumab. We determined crystal structures of these
      DARPins in complex with the respective subdomains. Detailed models of the full
      length receptor, constrained by its rigid domain structures and its membrane
      anchoring, explain how the bispecific DARPins connect two membrane-bound HER2
      molecules, distorting them such that they cannot form signaling-competent dimers
      with any EGFR family member, preventing any kinase dimerization, and thus leading
      to a complete loss of signaling. 

PMID- 24095060
TI  - EcxAB is a founding member of a new family of metalloprotease AB5 toxins with a
      hybrid cholera-like B subunit.
AB  - AB5 toxins are composed of an enzymatic A subunit that disrupts cellular function
      associated with a pentameric B subunit required for host cell invasion. EcxAB is
      an AB5 toxin isolated from clinical strains of Escherichia coli classified as
      part of the cholera family due to B subunit homology. Cholera-group toxins have
      catalytic ADP-ribosyltransferases as their A subunits, so it was surprising that
      EcxA did not. We confirmed that EcxAB self-associates as a functional toxin and
      obtained its structure. EcxAB is a prototypical member of a hybrid AB5 toxin
      family containing metzincin-type metalloproteases as their active A subunit
      paired to a cholera-like B subunit. Furthermore, EcxA is distinct from previously
      characterized proteases and thus founds an AB5-associated metzincin family that
      we term the toxilysins. EcxAB provides the first observation of conserved B
      subunit usage across different AB5 toxin families and provides evidence that the
      intersubunit interface of these toxins is far more permissive than previously
      supposed. 

PMID- 24095061
TI  - Structural determinants for geometry and information decoding of tRNA by T box
      leader RNA.
AB  - T box riboswitches are cis-acting RNA elements that bind to tRNA and sense its
      aminoacylation state to influence gene expression. Here, we present the 3.2 A
      resolution X-ray crystal structures of the T box Stem I-tRNA complex and tRNA, in
      isolation. T box Stem I forms an arched conformation with extensive
      intermolecular contacts to two key points of tRNA, the anticodon and D/T-loops.
      Free and complexed tRNA exist in significantly different conformations, with the
      contacts stabilizing flexible D/T-loops and a rearrangement of the D-loop. Using
      a designed T box RNA/tRNA system, we demonstrate that the T box riboswitch
      monitors the length and orientation of two essential contacts. Length or
      orientation mismatches engineered into the T box riboswitch and tRNA disrupt the
      complex, whereas simultaneous insertion of full helical turns realigns the
      interfaces and restores interaction between artificially elongated T box
      riboswitch and tRNA molecules. 

PMID- 24095062
TI  - Alternative bearings in total hip arthroplasty in the young patient.
AB  - Total hip arthroplasty is an effective treatment option for advanced hip
      arthritis in elderly patients. Studies in young patients have traditionally shown
      less durable results. With current implants, surgical technique, and cementless
      fixation methods, the durability of total hip arthroplasty may now be related to
      the wear performance of the bearing surfaces. To improve implant longevity, there
      are several bearing surface choices currently available for this demanding group
      of patients. Alternatives must be evaluated in terms of the risks and benefits
      associated with each articulation, and all new technologies must be carefully
      monitored over the long term. 

PMID- 24095063
TI  - Osteonecrosis of the hip: treatment options and outcomes.
AB  - This article reviews the literature regarding the outcomes of various
      nonoperative and operative treatment options for osteonecrosis of the hip. This
      article provides the orthopedic community with the latest evidence regarding the
      suitability of currently available treatment modalities in various stages of the
      disease. 

PMID- 24095064
TI  - Management of labral tears of the hip in young patients.
AB  - Our understanding of labral tears in young patients has evolved significantly in
      recent years. Successful outcome depends on addressing all bony impingement to
      improve the intra-articular environment, and prevent further damage to the labrum
      and articular cartilage. Improved clinical outcomes are associated with labral
      repair; in cases of a deficient labrum, arthroscopic reconstruction techniques
      have been developed, with promising clinical outcomes. This article reviews the
      anatomy of the acetabular labrum, and discusses the pathogenesis of labral tears
      as well as various treatment options, including arthroscopic labral repair and
      reconstruction. 

PMID- 24095065
TI  - Arthroscopy of the hip: factors affecting outcome.
AB  - Hip arthroscopy is a rapidly progressing field that has advanced in function and
      survivorship over the past decade. As increasing literature is published on
      outcomes of hip arthroscopy, a retrospective review has allowed for the
      identification of factors that affect survivorship. Within this review, the
      authors present the factors identified to date that affect survivorship after hip
      arthroscopy while raising questions about the future direction of the field. 

PMID- 24095066
TI  - The evolution of damage control orthopedics: current evidence and practical
      applications of early appropriate care.
AB  - This article summarizes the evolution of literature and practice related to
      fracture care in polytrauma patients. Particular emphasis is given to the
      management of femoral shaft fractures and the concept of damage control in these
      complex patients. The application of these guidelines in common clinical practice
      is also discussed. 

PMID- 24095067
TI  - Weight bearing after a periarticular fracture: what is the evidence?
AB  - Orthopedic surgeons frequently provide weight-bearing recommendations to guide
      patient recovery following lower extremity fractures. This article discusses the
      available literature regarding the effects of early weight bearing on fracture
      healing, patient compliance with weight bearing restrictions, and the effect of
      different weight bearing protocols following acetabular, tibial plateau, tibial
      plafond, ankle, and calcaneus fractures. 

PMID- 24095068
TI  - Surgical treatment of talus fractures.
AB  - Talus fractures result from high-energy mechanisms and usually occur at the neck.
      Functional outcome after talar neck fracture worsens with increasing Hawkins
      grade. The mainstay of treatment for talar neck fractures is anatomic reduction
      and internal fixation. Prompt reduction of dislocations should be performed.
      Patients should be taken to the operating room as soon as stabilized. Dual
      incisions and a combination of minifragment plates and screws should be used.
      Talar body fractures have a high rate of ankle and subtalar arthritis. Lateral
      process fractures are frequently missed on radiographs. Complications after talus
      fractures include osteonecrosis, malunion, post-traumatic arthritis, and
      infection. 

PMID- 24095069
TI  - Surgical management principles of gunshot-related fractures.
AB  - This article discusses contemporary management strategies for gunshot-related
      fractures with special attention paid to the initial evaluation, role of
      debridement, principles of fixation, need and duration of antibiotic therapy, and
      management of sequelae. Pertinent sequelae detailed are fractures associated with
      vascular injury, compartment syndrome, massive loss of soft tissue and bone,
      nerve injury, and lead toxicity. 

PMID- 24095070
TI  - Spectrum of shoulder injuries in skeletally immature patients.
AB  - This article evaluates the spectrum of epidemiology and treatment of children
      presenting with shoulder pain. These injuries are discussed to further understand
      the mechanism of injury, the variation of these injuries with age, treatment
      options, and outcomes and complications that may arise. A retrospective clinical
      review was performed to compliment the findings of the literature review. 

PMID- 24095072
TI  - Advances in the orthopedic management of osteogenesis imperfecta.
AB  - The long-established study of osteogenesis imperfecta (OI) has opened a realm of
      scientific research surrounding connective tissue disorders. Over the past decade
      alone there have been vast advancements in the understanding of the underlying
      genetic variations of this disease, pharmacologic treatments, and the
      technological and surgical options for fracture deformity. It is important to
      appreciate the progressive nature of the advances concerning OI. This article
      aims to synthesize the expanding evolution of the field surrounding OI over the
      past decade. 

PMID- 24095073
TI  - Femoroacetabular impingement: current concepts and controversies.
AB  - The concept of femoroacetabular impingement (FAI) emerged following the
      observation that FAI can be precipitated by acetabular reorientation and can
      produce new labral damage. Interest in the association between chondrolabral
      damage and variations in femoral and acetabular anatomy has established a causal
      relationship between mechanical aberration in the function of the hip joint and
      the development of labral and cartilage damage. The accepted definition of FAI is
      that it is characterized by abnormal mechanical contact between the rim of the
      acetabulum and the upper femur. Combinations of certain morphologies and
      movements may lead to FAI. 

PMID- 24095071
TI  - Prevention of overuse sports injuries in the young athlete.
AB  - The purpose of this article is to review the current theories regarding
      prevalence, mechanism, and prevention strategies for overuse injuries in a young
      athletic population. This information provides valuable insight into the state of
      the current evidence regarding overuse injuries in young athletes as well as the
      potential future directions in the development of overuse injury prevention
      interventions. 

PMID- 24095074
TI  - Adult brachial plexus injury: evaluation and management.
AB  - Adult traumatic brachial plexus injury involves injury of the C5-T1 spinal
      nerves. Common patterns of injury include "upper arm" and "total arm" types. The
      specific signs of preganglionic avulsion injury infer a poor prognosis for
      spontaneous recovery and surgery may be needed. Detailed preoperative evaluation
      is recommended for localization of the lesions. The treatment of upper arm type
      injury comprises restoration of elbow flexion and shoulder control. Good
      functional results may be achieved after multiple nerve transfers. The treatment
      of total arm type includes hand function reconstruction, in addition to shoulder
      and elbow treatment. Current options for hand function reconstruction include
      functioning free muscle transfers and nerve transfers. 

PMID- 24095075
TI  - Orthopedic evaluation and surgical treatment of the spastic shoulder.
AB  - The spastic shoulder can often result from brain injury that causes disruption in
      the upper motor neuron inhibitory pathways. Patients develop dyssynergic muscle
      activation, muscle weakness, and contractures and often present with fixed
      adduction and internal rotation deformity to the limb. This article reviews the
      importance of a comprehensive preoperative evaluation and discusses appropriate
      treatment strategies based on preoperative evaluation. 

PMID- 24095076
TI  - Lateral epicondylitis: review of injection therapies.
AB  - Lateral epicondylitis has several different treatment methods, with no single
      agreed upon therapy. This article summarizes the current literature on injection
      therapies for lateral epicondylitis. Glucocorticoid, botulinum toxin, autologous
      blood, platelet-rich plasma, hyaluronic acid, polidocanol, glycosaminoglycan, and
      prolotherapy injections are discussed. 

PMID- 24095077
TI  - Hand infections.
AB  - Many acute hand and upper extremity infections should be treated as surgical
      emergencies to avoid stiffness, contracture, pain, and amputation. Proper
      treatment requires understanding of anatomy and how this influences the behavior
      of certain infections, common offending organisms, antibiotic treatment,
      management of host factors, and surgical intervention. This article reviews the
      microbiology, antibiotic coverage, and surgical treatment of the most common
      infections in the hand: paronychia, felon, herpetic whitlow, flexor
      tenosynovitis, deep space infections, septic arthritis, bites from humans and
      animals, necrotizing fasciitis, mycobacterium infections, and fungal infections.
      Recommendations are based on the most recent available evidence. 

PMID- 24095078
TI  - Os acromiale: a review and an introduction of a new surgical technique for
      management.
AB  - Os acromiale is a common finding in shoulder surgery. We review the anatomy,
      prevalence, pathophysiology, and treatment options for this diagnosis. In
      addition, we report on a case series of 6 patients with a symptomatic meso os
      acromiale who were treated with a new technique involving arthroscopic
      acromioplasty in conjunction with the excision of the acromial nonunion site. We
      have demonstrated this novel treatment method to be a safe and effective
      technique in this case series. This arthroscopic partial resection of an os
      acromiale is considered to be an alternative option for treating a symptomatic
      meso os acromiale. 

PMID- 24095079
TI  - How intraoperative navigation is changing musculoskeletal tumor surgery.
AB  - Computer-assisted orthopedic surgery (CAOS) was introduced, developed, and
      implemented in musculoskeletal tumor surgery recently to enhance surgical
      precision in resecting malignant and benign tumors. The origins of computer
      assisted surgery were in other subspecialties including maxillofacial surgery,
      spine surgery, and arthroplasty. Early studies have shown that CAOS can also be
      used safely for bone tumor resection surgery. Additional technological
      improvements may allow use of CAOS in soft tissue tumor surgery. It has the
      potential to improve surgical precision and accuracy, but more study is needed to
      evaluate clinical efficacy and long term results. 

PMID- 24095080
TI  - Malignant soft tissue tumors in children.
AB  - Soft tissue masses are frequently seen in children. Although most are benign or
      reactive, soft tissue sarcomas (STS)-both rhabdomyosarcoma (most common) and non
      rhabdo STS, do occur in the extremities. Appropriate evaluation of extremity soft
      tissue tumors often includes a biopsy as the clinical and imaging features may
      not be enough to establish a definitive diagnosis. Much needs to be done for
      improving the treatment of these rare but often devastating sarcomas. Given the
      small numbers of these cases seen at various centers, collaborative efforts
      should be made to further our understanding and improve the management of these
      challenging cases. 

PMID- 24095081
TI  - Adult reconstruction.

PMID- 24095082
TI  - Preface. Upper extremity.

PMID- 24095083
TI  - Trauma section.

PMID- 24095084
TI  - Preface. SLAP IV tear.

PMID- 24095085
TI  - Preface. Oncology section.

PMID- 24095086
TI  - Clinical implication of T2* cardiac magnetic resonance imaging in cardiac
      siderosis.

PMID- 24095087
TI  - Pancytopenia in secondary hyperparathyroidism due to end-stage renal disease.

PMID- 24095088
TI  - Pharmacist consultations in general practice clinics: the Pharmacists in Practice
      Study (PIPS).
AB  - BACKGROUND: Medication-related problems (MRPs) are a concern in primary care
      settings. Pharmacists based in the community or community pharmacies are able to
      identify, resolve and prevent MRPs; however, the lack of a formal partnership
      with physicians and poor access to patients' medical records are limitations. In
      Australia, delivery of pharmacist services within general practice clinics is
      rare. OBJECTIVES: To evaluate the effectiveness of consultations by pharmacists
      based within primary care medical practices. METHODS: A prospective, before-after
      intervention study was conducted at two primary health care (general practice)
      clinics in Melbourne, Australia. Participants were clinic patients who had risk
      factors for MRPs (e.g. polypharmacy). Patients received a consultation with the
      pharmacist in a private consulting room at the clinic or in their home. The
      pharmacist reviewed the patient's medication regimen and adherence, with full
      access to their medical record, provided patient education, and produced a report
      for the general practitioner. The primary outcome was the number of MRPs
      identified by the pharmacist, and the number that remained unresolved 6 months
      after the pharmacist consultation. Secondary outcomes included medication
      adherence, health service use, and patient satisfaction. RESULTS: Eighty-two
      patients were recruited and 62 (75.6%) completed the study. The median number of
      MRPs per patient identified by the practice pharmacist was 2 (interquartile range
      [IQR] 1, 4). Six months after review, this fell to 0 (IQR 0, 1), P < 0.001. The
      proportion of patients who were adherent to their medications improved
      significantly, according to both the Morisky (44.1% versus 62.7%, P = 0.023) and
      the Tool for Adherence Behaviour Screening (TABS) (35.6% versus 57.6%, P = 0.019)
      scales. There was no significant effect on health service use. Patients were
      highly satisfied with the pharmacist consultations. CONCLUSIONS: Consultations
      undertaken by pharmacists located within primary health care clinics were
      effective in identifying and resolving MRPs. The consultations were well received
      by patients and were associated with improvements in medication adherence.

PMID- 24095089
TI  - Overcoming doxorubicin-resistance in the NCI/ADR-RES model cancer cell line by
      novel anthracene-9,10-dione derivatives.
AB  - Overcoming drug resistance with remarkable cytotoxic activity by anthracene-9,10
      dione derivatives would offer a potential therapeutic strategy. In this study, we
      report the synthesis and the cytotoxicity of a novel set of anthraquninones. (4
      (4-Aminobenzylamino)-9,10-dioxo-9,10-dihydroanthracen-1-yl-4
      methylbenzenesulfonate) (3) has excellent in vitro cytotoxicity against
      doxorubicin-resistant cancer cell line (IC50=0.8 MUM), 20-fold higher than
      doxorubicin. The cytotoxic effect via G2/M arrest does not appear to be ROS.

PMID- 24095090
TI  - Novel bis-ortho-alkoxy-para-piperazinesubstituted-2,4-dianilinopyrimidines (KRCA
      0008) as potent and selective ALK inhibitors for anticancer treatment.
AB  - The synthesis of bis-ortho-alkoxy-para-piperazinesubstituted-2,4
      dianilinopyrimidines is described and their structure-activity-relationship to
      anaplastic lymphoma kinase (ALK) is presented. KRCA-0008 is selective and potent
      to ALK and Ack1, and displays drug-like properties without hERG liability. KRCA
      0008 demonstrates in vivo efficacy comparable to Crizotinib in xenograft mice
      model. 

PMID- 24095091
TI  - Rational drug design based synthesis of novel arylquinolines as anti-tuberculosis
      agents.
AB  - A series of novel arylquinoline derivatives was designed retaining significant
      pharmacophoric features and three dimensional geometry of bedaquiline. In silico
      ADME study was performed to assess drug likeness and toxicity profiles of the
      designed molecules. The compounds were evaluated for activity against
      Mycobacterium tuberculosis H37Rv using Resazurin Microtitre Assay (REMA) plate
      method and cytotoxicity in VERO C1008 cell line. Several of the synthesized
      compounds exhibited good antituberculosis activity and selectivity, especially
      compounds, 12i (MIC: 5.18 MUM and MIC/CC50: 152.86) and 12l (MIC: 5.59 MUM and
      MIC/CC50: 160.57). The study opens up a new platform for the development of
      arylquinoline based drugs for treating tuberculosis.

PMID- 24095092
TI  - Structure-activity relationships of the aromatic site in novel anticonvulsant
      pyrrolo[1,2-a]pyrazine derivatives.
AB  - Novel, chiral derivatives of pyrrolo[1,2-a]pyrazine with aromatic substituents at
      carbon C-4 were synthesized by a short synthetic sequence involving Ugi
      multicomponent reaction. The compounds were evaluated for their in vivo efficacy
      in animal models of epilepsy within the Anticonvulsant Screening Program (ASP).
      High activity in 'classical' maximal electroshock seizure (MES) and subcutaneous
      Metrazol (scMET) tests was characteristic for meta-substituted analogs. On the
      other hand, efficacy of compounds in the 6 Hz model of pharmacoresistant limbic
      seizures was only marginally affected by the orientation of substituents in the
      phenyl moiety. The most active derivative, 5a, displayed an ED50 value of 32.24
      mg/kg and a protective index of 6.6 (PI) in the 6 Hz test. It was also active in
      a pilocarpine-induced status prevention model of pharmacoresistant status
      epilepticus.

PMID- 24095093
TI  - The application of Heck reaction in the synthesis of guaianolide sesquiterpene
      lactones derivatives selectively inhibiting resistant acute leukemic cells.
AB  - A series of guaianolide-type sesquiterpene lactones derivatives with arylation of
      alpha-methylene-gamma-lactone moiety was synthesized using Heck reactions, and
      was evaluated for their activities against acute myelogenous leukemia (AML) cell
      line HL-60 and doxorubicin-resistant cell line HL-60/A. Although all compounds
      were significantly less active against HL-60 than the parent molecules,
      surprisingly, compounds 3a, 4c-4e, 5e, and 8d exhibited high potency against
      doxorubicin-resistant cell line HL-60/A (IC50=6.2-19 MUM), and their activities
      against HL-60/A were comparable to that of their parent molecules. In view of
      their novel activities against HL-60/A, compound 5e with inhibitory activity
      against HL-60/A (IC50=6.2+/-0.5 MUM) was selected for study its preliminary
      mechanism. The result reveals that compound 5e can obviously induce apoptosis.

PMID- 24095094
TI  - Methanolysis of triterpenoid saponin from Ardisia gigantifolia stapf. and
      structure-activity relationship study against cancer cells.
AB  - Thirteen 13,28-epoxy triterpenoid saponins were isolated from Ardisia
      gigantifolia stapf. and one potential anti-tumor saponin was methanolysised by
      H2SO4 to afford four new compounds. The seventeen compounds were evaluated for
      their anti-proliferative activity on A549, HCT-8 and Bel-7402 cells. The
      structure-activity relationship analysis indicated that the incorporation of =O
      group at C-16, L-rhamnose at R(5) and acetyl group at OH-6 of the D-glucose lead
      to a significant increase of the cytotoxic activity on A549 and HCT-8 but
      significant reduction of the cytotoxic activity on Bel-7402 cells. The
      synthesized saponins losing 13,28-epoxy and CHO at C-30, losed their
      cytotoxicities on A549 and HCT-8 cells, suggesting that the two moieties play an
      essential role for activity. 3beta-O-alpha-L-rhamnopyranosyl-(1->3)-[beta-D
      xylopyranosyl-(1->2)]-beta-D-glucopyranosyl-(1->4)-[beta-D-glucopyranosyl-(1->2)]
      alpha-l-arabinopyranoside-16alpha-hydroxy-13,28-epoxy-oleanane (2) showed better
      inhibitory activity to Bel-7402 (IC50 0.86 MUM) than that of 5-FU (IC50 8.30
      MUM), which indicate that five saccharide and methyl moiety at C-30 are important
      for anti-proliferative activity. The activities of saponins 15>14, 17>16,
      suggested that the configuration of 28,30-epoxy is preferable to be 30(R) rather
      than 30(S) on Bel-7402 cells. Further molecular mechanism studies of saponins 1
      and 2 were carried out on the cell cycle distribution of Bel-7402 cells.

PMID- 24095095
TI  - Synthesis and biological evaluation of novel pyrido[2,3-b]pyrazines inhibiting
      both erlotinib-sensitive and erlotinib-resistant cell lines.
AB  - A series of novel pyrido[2,3-b]pyrazines were synthesized as potential antitumor
      agents for erlotinib-resistant tumors. Known signal inhibitor compounds from our
      Nested Chemical Library were tested in phenotypic assays on erlotinib-sensitive
      PC9 and erlotinib-resistant PC9-ER cell lines to find a compound class to be
      active on erlotinib resistant cell lines. Based on the screening data, novel
      pyrido[2,3-b]pyrazines were designed and synthesized. The effect of the
      substituent position of the heteroaromatic moiety in position 7 and the
      importance of unsubstituted position 2 of the pyridopyrazine core were explored.
      Compound 7n had an IC50 value of 0.09 MUM for the inhibition of PC9 and 0.15 MUM
      for the inhibition of PC9-ER. We found that some lead compounds of these
      structures overcome erlotinib-resistance which might become promising drug
      candidates to fight against NSCLC with EGFR T790M mutation. The signaling
      network(s) involved in the mechanism(s) of action of these novel compounds in
      overcoming erlotinib resistance remain to be elucidated.

PMID- 24095096
TI  - Synthesis and in vitro evaluation of a novel radioligand for alphavbeta3 integrin
      receptor imaging: [18F]FPPA-c(RGDfK).
AB  - The development of RGD-based antagonist of alphavbeta3 integrin receptor has
      enhanced the interest in PET probes to image this receptor for the early
      detection of cancer, to monitor the disease progression and the response to
      therapy. In this work, a novel prosthetic group (N-(4-fluorophenyl)pent-4-ynamide
      or FPPA) for the (18)F-labeling of an alphavbeta3 selective RGD-peptide was
      successfully prepared. [(18)F]FPPA was obtained in three steps with a
      radiochemical yield of 44% (decay corrected). Conjugation to c(RGDfK(N3)) by the
      Cu(II) catalyzed Huisgen azido alkyne cycloaddition provided the [(18)F]FPPA
      c(RGDfK) with a radiochemical yield of 29% (decay corrected), in an overall
      synthesis time of 140 min.

PMID- 24095097
TI  - Synthesis of eco-friendly CuInS2 quantum dot-sensitized solar cells by a combined
      ex situ/in situ growth approach.
AB  - A cadmium-free CuInS2 quantum dot (QD)-sensitized solar cell (QDSC) has been
      fabricated by taking advantage of the ex situ synthesis approach for fabricating
      highly crystalline QDs and the in situ successive ionic-layer adsorption and
      reaction (SILAR) approach for achieving high surface coverage of QDs. The ex situ
      synthesized CuInS2 QDs can be rendered water soluble through a simple and rapid
      two-step method under the assistance of ultrasonication. This approach allows a
      stepwise ligand change from the insertion of a foreign ligand to ligand
      replacement, which preserves the long-term stability of colloidal solutions for
      more than 1 month. Furthermore, the resulting QDs can be utilized as sensitizers
      in QDSCs, and such a QDSC can deliver a power conversion efficiency (PCE) of
      0.64%. Using the SILAR process, in situ CuInS2 QDs could be preferentially grown
      epitaxially on the pre-existing seeds of ex situ synthesized CuInS2 QDs. The
      results indicated that the CuInS2 QDSC fabricated by the combined ex situ/in situ
      growth process exhibited a PCE of 1.84% (short-circuit current density = 7.72 mA
      cm(-2), open-circuit voltage = 570 mV, and fill factor = 41.8%), which is higher
      than the PCEs of CuInS2 QDSCs fabricated by ex situ and in situ growth processes,
      respectively. The relative efficiencies of electrons injected by the combined ex
      situ/in situ growth approach were higher than those of ex situ synthesized CuInS2
      QDs deposited on TiO2 films, as determined by emission-decay kinetic
      measurements. The incident photon-to-current conversion efficiency has been
      determined, and electrochemical impedance spectroscopy has been carried out to
      investigate the photovoltaic behavior and charge-transfer resistance of the
      QDSCs. The results suggest that the combined synergetic effects of in situ and ex
      situ CuInS2 QD growth facilitate more electron injection from the QD sensitizers
      into TiO2. 

PMID- 24095099
TI  - Lumbar lordosis.
AB  - Lumbar lordosis is a key postural component that has interested both clinicians
      and researchers for many years. Despite its wide use in assessing postural
      abnormalities, there remain many unanswered questions regarding lumbar lordosis
      measurements. Therefore, in this article we reviewed different factors associated
      with the lordosis angle based on existing literature and determined normal values
      of lordosis. We reviewed more than 120 articles that measure and describe the
      different factors associated with the lumbar lordosis angle. Because of a variety
      of factors influencing the evaluation of lumbar lordosis such as how to position
      the patient and the number of vertebrae included in the calculation, we recommend
      establishing a uniform method of evaluating the lordosis angle. Based on our
      review, it seems that the optimal position for radiologic measurement of lordosis
      is standing with arms supported while shoulders are flexed at a 30 degrees 
      angle. There is evidence that many factors, such as age, gender, body mass index,
      ethnicity, and sport, may affect the lordosis angle, making it difficult to
      determine uniform normal values. Normal lordosis should be determined based on
      the specific characteristics of each individual; we therefore presented normal
      lordosis values for different groups/populations. There is also evidence that the
      lumbar lordosis angle is positively and significantly associated with
      spondylolysis and isthmic spondylolisthesis. However, no association has been
      found with other spinal degenerative features. Inconclusive evidence exists for
      association between lordosis and low back pain. Additional studies are needed to
      evaluate these associations. The optimal lordotic range remains unknown and may
      be related to a variety of individual factors such as weight, activity, muscular
      strength, and flexibility of the spine and lower extremities. 

PMID- 24095098
TI  - Artificial neural networks assessing adolescent idiopathic scoliosis: comparison
      with Lenke classification.
AB  - BACKGROUND CONTEXT: Variability in classifying and selecting levels of fusion in
      adolescent idiopathic scoliosis (AIS) has been repeatedly documented. Several
      computer algorithms have been used to classify AIS based on the geometrical
      features, but none have attempted to analyze its treatment patterns. PURPOSE: To
      use self-organizing maps (SOM), a kind of artificial neural networks, to reliably
      classify AIS cases from a large database. To analyze surgeon's treatment pattern
      in selecting curve regions to fuse in AIS using Lenke classification and SOM.
      STUDY DESIGN: This is a technical concept article on the possibility and benefits
      of using neural networks to classify AIS and a retrospective analysis of AIS
      curve regions selected for fusion. PATIENT SAMPLE: A total of 1,776 patients
      surgically treated for AIS were prospectively enrolled in a multicentric
      database. Cobb angles were measured on AIS patient spine radiographies, and
      patients were classified according to Lenke classification. OUTCOME MEASURES: For
      each patient in the database, surgical approach and levels of fusion selected by
      the treating surgeon were recorded. METHODS: A Kohonen SOM was generated using
      1,776 surgically treated AIS cases. The quality of the SOM was tested using
      topological error. Percentages of prediction of fusion based on Lenke
      classification for each patient in the database and for each node in the SOM were
      calculated. Lenke curve types, treatment pattern, and kappa statistics for
      agreement between fusion realized and fusion recommended by Lenke classification
      were plotted on each node of the map. RESULTS: The topographic error for the SOM
      generated was 0.02, which demonstrates high accuracy. The SOM differentiates
      clear clusters of curve type nodes on the map. The SOM also shows epicenters for
      main thoracic, double thoracic, and thoracolumbar/lumbar curve types and
      transition zones between clusters. When cases are taken individually, Lenke
      classification predicted curve regions fused by the surgeon in 46% of cases. When
      those cases are reorganized by the SOM into nodes, Lenke classification predicted
      the curve regions to fuse in 82% of the nodes. Agreement with Lenke
      classification principles was high in epicenters for curve types 1, 2, and 5,
      moderate in cluster for curve types 3, 4, and 6, and low in transition zones
      between curve types. CONCLUSIONS: An AIS SOM with high accuracy was successfully
      generated. Lenke classification principles are followed in 46% of the cases but
      in 82% of the nodes on the SOM. The SOM highlights the tendency of surgeons to
      follow Lenke classification principles for similar curves on the SOM. Self
      organizing map classification of AIS could be valuable to surgeons because it
      bypasses the limitations imposed by rigid classification such as cutoff values on
      Cobb angle to define curve types. It can extract similar cases from large
      databases to analyze and guide treatment.

PMID- 24095100
TI  - Craniocervical hyperpneumatization with concurrent pneumorrhachis,
      pneumomediastinum, and subcutaneous emphysema in a weightlifter.
AB  - BACKGROUND CONTEXT: Acquired hyperpneumatization of the skull base and upper
      cervical vertebrae is extremely rare and is thought to occur in patients who
      habitually perform the Valsalva maneuver or engage in repetitive positive
      pressure activities such as scuba diving or free diving. Craniocervical
      hyperpneumatization has been reported to cause intracranial and extracranial
      pneumatoceles but is not generally considered as a cause of pneumorrhachis (air
      in the spinal canal). Pneumorrhachis is relatively rare, and usually occurs in a
      localized form, either in the cervical spine secondary to skull base fractures or
      in the thoracic spine secondary to pneumomediastinum or pneumothorax. Here, we
      report a case of extensive pneumorrhachis extending from the skull base to the
      thoracolumbar junction in association with marked axio-atlanto-occipital
      hyperpneumatization and pneumomediastinum. This unique constellation of findings
      likely resulted from complications of the Valsalva maneuver during strenuous
      exercise. PURPOSE: To present a unique case of axio-atlanto-occipital
      hyperpneumatization with concurrent marked cervicothoracic pneumorrhachis,
      subcutaneous emphysema, and pneumomediastinum and to provide a review of the
      relevant literature, pathophysiology, and treatment strategies related to
      hyperpneumatization and pneumorrhachis. STUDY DESIGN/SETTING: A unique case
      report from an urban medical center. PATIENT SAMPLE: A single case. OUTCOME
      MEASURES: Imaging findings and clinical history. METHODS: Imaging data from a
      picture archiving and communication system and clinical data from an electronic
      medical record system were analyzed. RESULTS: A 58-year-old previously healthy
      man presented with 3 to 4 weeks of neck pain, shoulder pain, and intermittent
      hand and finger numbness that developed after weightlifting. On physical
      examination, he had mild hyperreflexia and decreased pinprick sensation within
      the T5-T8 dermatomes. Initial radiographic and computed tomography (CT) studies
      demonstrated extensive craniocervical hyperpneumatization involving the occipital
      bone, clivus, and C1 and C2 vertebral bodies. There was also pneumorrhachis
      extending throughout the entire cervical and thoracic spine, which caused
      moderate dural compression. Pneumomediastinum and subcutaneous emphysema were
      present. Maxillofacial CT showed dehiscent bone involving the dens, atlas, and
      occipital bone, with adjacent soft-tissue gas and pneumorrhachis. He was managed
      conservatively and advised to stop performing the Valsalva maneuver during
      weightlifting. His symptoms resolved, and follow-up imaging showed complete
      resolution of pneumorrhachis and partial reversal of hyperpneumatization.
      CONCLUSIONS: Craniocervical hyperpneumatization is a rare complication of the
      Valsalva maneuver. Most reported cases have involved only the skull base, or the
      skull base and C1, and many have been further complicated by microfractures
      leading to pneumocephalus or extracranial pneumatoceles. We present a unique case
      of extensive craniocervical hyperpneumatization that extended to the level of C2
      and was complicated by microfractures causing severe pneumorrhachis. Concurrent
      pneumomediastinum in this case may have been an independent complication of the
      Valsalva maneuver, which could have contributed to pneumorrhachis. Alternatively,
      pneumomediastinum may have been caused by migration of gas through the neural
      foramen from the epidural space, driven by positive pressure generated by the one
      way valve effect of the Eustachian tube during periods of exertion.

PMID- 24095101
TI  - Clinical and radiographic outcomes of cervical disc replacement with a new
      prosthesis.
AB  - BACKGROUND CONTEXT: Anterior cervical discectomy and interbody fusion was a
      classical treatment for cervical degenerative disc disease (CDDD). However, the
      rigid fusion also leads to a reduction in normal cervical spine motion and to
      increased biomechanical stress at adjacent levels, which in turn accelerates
      degenerative changes of the discs at these levels. Cervical disc replacement
      (CDR) is a new technology with the aim of addressing the limitations of fusion
      procession and preserving motion at the treated level. Discover prosthesis (DePuy
      Spine, Raynham, MA, USA) is a new type artificial disc and there are few reports
      about it. PURPOSE: The purpose of this study was to analyze the primary clinical
      and radiographic outcomes of CDR with Discover prosthesis to treat mono- or bi
      segment CDDD in a Chinese population. STUDY DESIGN: The study design was
      prospective and single-center clinical trial of the Discover prosthesis in the
      treatment of patients with mono- or bi-segment CDDD. PATIENTS SAMPLE: Seventy
      nine patients with 102 Discover prosthesis arthroplasty performed (56 mono
      segment and 23 bi-segment) were evaluated. OUTCOME MEASURES: Clinical outcomes
      based on Japanese Orthopaedic Association (JOA), visual analog scale (VAS) pain
      score, and Odom's scale and radiographic outcomes including the anterior disc
      heights (ADH), posterior disc heights (PDH), range of motion, and performance of
      heterotopic ossification (HO) of the operative segment were assessed. METHODS:
      Clinical and radiographic follow-up was performed. Preoperative and postoperative
      ADH, PDH, and range of motion were measured from lateral and flexion-extension
      radiographs. The paired t test was used to assess the difference of clinical and
      radiographic outcomes before and after operation. The performance of HO was
      observed by two independent MD. RESULTS: The mean follow-up time for all the
      patients was 31.6 months, ranging from 24 to 43 months. Mean preoperative JOA
      score was 9.5, and VAS overall pain score was 7.2. At 2-, 6-, 12-, and 24-month
      follow-up, the mean JOA score was 14.1, 14.7, 15.3, and 14.9, whereas the mean
      VAS overall pain score was 1.9, 1.7, 1.8, and 1.4, respectively. Mean JOA and VAS
      scores showed statistical improvements in the postoperative period. Seven
      patients had mild dysphagia within the first month after operation. According to
      Odom's scale, 52 patients had excellent outcomes, 25 patients had good outcomes,
      and 2 patients had fair outcomes at 2-year follow-up. The Mean preoperative ADH
      and PDH of the operative segment were 4.9 mm and 3.1 mm. Compared with
      preoperative, there were significantly increased and maintenance well at 2- (7.5
      mm, 5.1 mm), 6- (7.5 mm, 5.0 mm), 12- (7.4 mm, 4.9 mm) and 24-month (7.2 mm, 5.0
      mm) follow-up. Range of motion of the operative segment in the postoperative
      follow-up was slightly increased than the preoperative follow-up but not
      statistically significant. Heterotopic ossification was presented in six replaced
      levels at 1-year follow-up including 4 Grade I and 2 Grade II and 18 replaced
      levels at the follow-up more than 2 years including 8 grade I and 10 grade II. No
      prosthesis subsidence or excursion was identified. CONCLUSIONS: The use of
      Discover prostheses in our study resulted in satisfactory clinical and
      radiographic outcomes. The prostheses can restore and maintain interbody height,
      while preserve the motion of the treated segment. Although the results of this
      study demonstrate initial safety and effectiveness in a Chinese population, we
      need further studies to know more about the impact of CDR with Discover
      prosthesis, especially on HO and adjacent segment degeneration.

PMID- 24095102
TI  - The effects of backpack load and carrying method on the balance of adolescent
      idiopathic scoliosis subjects.
AB  - BACKGROUND CONTEXT: Concerns have been raised about the effect of backpack
      carrying on adolescent balance. For adolescent idiopathic scoliosis (AIS)
      subjects, the effect of backpack carrying method on their balance has not been
      determined. Our aim is to examine the effects of backpack load and carrying
      method on AIS subjects' balance. STUDY DESIGN/SETTING: Paired sample matched for
      age and sex. PATIENT SAMPLE: Twelve healthy adolescents matched for age and sex
      with 14 adolescents with mild AIS participated in this study. OUTCOME MEASURES: A
      test battery including clinical examination, radiological assessment, and
      stabilometric measurements of the postural sways in the upright standing posture
      were conducted. METHODS: Center of pressure excursions of our subjects were
      recorded with a stabilometric platform during the upright standing posture
      without a backpack and while carrying a backpack symmetrically and asymmetrically
      on each shoulder. For each carrying method, the backpack is loaded at 10% and 15%
      of body weight (BW). RESULTS: Our results indicated that postural sways increased
      with increasing backpack load. These postural sways were observed when normal
      adolescents carried a backpack loaded with 15% BW load, whereas, for age- and sex
      matched AIS subjects, these postural responses were observed for the 10% BW load.
      The symmetrical backpack carrying induced better balance compared with the
      asymmetrical one. Asymmetrical carrying on the convex side of the scoliotic curve
      affects AIS subjects' balance more than carrying it on the concave side.
      CONCLUSIONS: Load carriage of 10% BW seems to alter AIS subjects' balance.
      Asymmetrical carrying should be avoided especially on the convex side of the
      scoliotic curve because it causes balance impairments that may increase spinal
      pain.

PMID- 24095103
TI  - Are adults with bipolar disorder active? Objectively measured physical activity
      and sedentary behavior using accelerometry.
AB  - BACKGROUND: Little is known about physical activity and sedentary behavior of
      adults with bipolar disorder (BP). Physical activity and sedentary behaviors may
      be modifiable factors associated with elevated rates of obesity, diabetes,
      cardiovascular disease, metabolic syndrome, and mortality in adults with BP.
      METHODS: Sixty adult outpatients treated for BP (> 18 yr) wore accelerometers for
      seven consecutive days. Each minute epoch was assigned an activity level based on
      the number of counts per minute; sedentary(<100 counts), light(101-1951 counts),
      or moderate/vigorous(>1952 counts). Adults with BP were matched 1:1 to users and
      non-users of mental health services (MHS) (NHANES 2003-2004) by gender, closest
      BMI, and age. RESULTS: On average, adults with BP wore actigraphs over 17 h/day.
      The majority of monitoring time (78%) was classified as sedentary (approximately
      13.5h/day). Light physical activity accounted for 21% of the monitoring time/day
      (215 min/day). None achieved 150 min/wk of moderate/vigorous activity as
      recommended by national guidelines. Adults with BP were significantly less active
      and more sedentary than MHS users and non-users in NHANES 2003-2004 (p<0.01).
      LIMITATIONS: Majority of the participants were relatively asymptomatic with most
      (87%) having no more than mild depressive symptoms and none experiencing severe
      manic symptoms. The sedating effects of medications on physical activity were not
      investigated. CONCLUSION: From clinical perspectives, these findings justify
      physical activity interventions targeting adults with BP as a possible means to
      improve their physical and mental health and to reduce the elevated risk of
      commonly observed medical comorbidities in this high-risk population.

PMID- 24095104
TI  - Liver metastases in close contact to hepatic veins ablated under vascular
      exclusion.
AB  - BACKGROUND: Liver metastases (LM) in close contact to hepatic veins (HV) are a
      frequent cause of unresectability. Reconstruction of hepatic veins is technically
      difficult and outcomes are poor. Intra-operative radiofrequency ablation (IRFA)
      with vascular exclusion (VE) may be a useful approach. METHODS: Out of 358
      patients operated for LM, 22 with LM close to a HV treated by IRFA under VE with
      at least one year of follow-up were included in this retrospective study.
      Technical success was evaluated at four months by CT scan of the ablated lesion.
      Complications; local, hepatic and extra-hepatic recurrence rates, and overall
      survival are reported. RESULTS: The median number of metastases was 4.5 [range: 1
      12]. Seventeen patients had bilateral metastases. The median size of ablated
      lesions was 2 cm [range: 1-5.5]. Seven complications occurred (1 Grade 1, 2 Grade
      3b and 4 Grade IVa), with no mortality. No recurrence of ablated lesions was
      detected at four months or during follow-up. Seventeen patients had new or extra
      hepatic lesions. Median overall survival for colorectal patients was 40 months
      95%CI[17.5-not reached]. CONCLUSIONS: IRFA plus VE for LM in close contact to a
      HV is a novel approach, appearing to be a safe and effective technique which can
      extend the applications of liver metastases surgery.

PMID- 24095105
TI  - Recommendations for early diagnosis and intervention in autism spectrum
      disorders: an Italian-Israeli consensus conference.
AB  - On April 2013 experts in the field of autism from Italy and Israel convened in
      Jerusalem to discuss and finalize clinical recommendations for early diagnosis
      and intervention in Autism Spectrum Disorders (ASDs). In this paper, we summarize
      the results of this Italian-Israeli consensus conference. ASDs constitute a class
      of severe and heterogeneous neurodevelopmental conditions caused by atypical
      brain development beginning during early prenatal life, reflecting many genetic,
      neurobiological and environmental influences. The first clinical signs of ASDs
      begin to be evident in children between 12 and 18 months of age, often after a
      period of relatively typical postnatal development. Recent longitudinal studies
      reveal substantial diversity in developmental trajectories through childhood and
      adolescence. Some intervention approaches have been demonstrated to be effective
      in improving core symptoms of ASDs, even if the heterogeneity and developmental
      nature of the disorder make it implausible that only one specific treatment will
      be best for all children with ASDs. More randomized control trials (RCTs) on
      early intervention are needed to identify the most effective strategies and
      provide the most efficient allocation of resources during the critical early
      intervention time period. Future research should focus on linking biological
      phenotypes with specific genotypes, thus establishing a foundation for the
      development of diagnostic screening tools and individualization of treatments. 

PMID- 24095106
TI  - [Superficial ulnar artery while harvesting a radial forearm flap].
AB  - Forearm vascular anatomical variations are common and may have complications
      during flaps harvesting. This article describes the presence of an ulnar
      superficial artery, revealed while harvesting a radial forearm flap. The
      prevalence of this anatomical variation is between 0.7 and 9.4%. It may have
      important consequences while covering loss of substance with a radial forearm
      flap. Unknown, there is a risk of vascular injury which may lead to distal
      ischemia of the upper limb. Preoperative diagnosis can anticipate this risk and
      harvest a fascio-cutaneous flap centered on a perforator of this artery. 

PMID- 24095107
TI  - Vascular training profiles across Europe.
AB  - BACKGROUND: The European Vascular Surgeons in Training (EVST) were appointed by
      the European Society for Vascular Surgery to review the current status and
      developments regarding training and certification in vascular surgery (VS) across
      Europe. METHODS: An e-mail-based survey was distributed to EVST representatives
      in 33 countries. The questionnaire examined the current structure of vascular
      surgery training and certification (monospecialty, subspecialty, no specialty),
      as well as the evolving revisions of national curricula. Questionnaires were
      returned from 31 countries, two of which implement two training models. RESULTS:
      Vascular surgery (VS) as a monospecialty is the leading training model in 18 out
      of 31 countries, nine countries follow the subspecialty model, and six countries
      have no accredited vascular programs. The mean duration of dedicated VS training
      in monospecialty is significantly longer compared with subspecialty (3.8 vs. 2.9
      years, p = .036) or no specialty models (3.8 vs. 1 years, p < .001). 83% of
      countries implementing an independent certification have recently updated their
      training curriculum; the respective rates for countries implementing a
      subspecialty or no specialty model are 56% and 17%. Among countries that offer VS
      certification, the endovascular logbook is mandatory in 78%, quality control of
      training centers or trainers is implemented in 62%, and training centers are
      reported as heterogeneous in 46%. The Working Time Directive is followed by
      vascular trainees in 10/24 EU countries. CONCLUSIONS: The results of this survey
      represent the most updated detailed record of the European training profiles in
      VS and document the diversity of vascular training across Europe.

PMID- 24095109
TI  - A case of intracystic apocrine papillary tumor: diagnostic pitfalls for
      malignancy.
AB  - Intraductal/intracystic papillary carcinoma (IPC) of the breast is defined as a
      malignant non-invasive papillary tumor arising from the ductal-lobular system.
      Based on the presence of myoepithelial cells in the cystic wall, IPC is
      distinguished from encapsulated papillary carcinoma (EPC). Here, we report a case
      of an intracystic apocrine papillary tumor in the breast of a 49-year-old woman.
      Histopathologic examination revealed that the entire papillary structures and
      cyst wall were comprised of apocrine cells, some of which showed nuclear atypia
      with macronucleoli. Immunohistochemical examination revealed a lack of
      myoepithelial cells in the papillary fronds and cyst wall. Although the dense
      proliferation of apocrine cells mimicked a cribriform pattern, detailed
      examination identified a delicately intermingled interstitium in the cribriform
      like growth area in the present case. We judged the current case to be benign
      apocrine papilloma. Only a few apocrine variants of IPC or EPC have been reported
      to be malignant or potentially malignant. Since even benign apocrine lesions are
      known to lack myoepithelial cells, histopathologic evaluation regarding malignant
      potential requires caution in apocrine variants. The detection of clearly benign
      areas and knowledge of the "pseudo-cribriform" pattern should provide clues to
      distinguish between benign and malignant apocrine papillary tumors.

PMID- 24095108
TI  - Comparative evaluation of dental resin composites based on micron- and submicron
      sized monomodal glass filler particles.
AB  - OBJECTIVES: A model resin composite containing a novel monomodal inorganic filler
      system based on submicron-sized Ba-Si-Al glass particles (NanoFine NF180; Schott)
      was formulated and compared with an experimental composite containing micron
      sized particles (UltraFine UF1.0; Schott). METHODS: The filler particles were
      characterized using X-ray microanalysis and granulometry, while the composites
      were characterized in terms of filler-resin morphology, radiopacity, degree of CC
      conversion, hardness, flexural strength/modulus, work-of-fracture, surface
      roughness and gloss (before and after simulated toothbrushing abrasion), and bulk
      compressive creep. The composites were formulated from the same photoactivated
      dimethacrylate co-monomer, incorporating mass fractions of 75% micron- and 78%
      submicron-sized particles. Quantitative data were analyzed at a significance
      level of p<0.05. RESULTS: Both filler systems exhibited a narrow grain size range
      (175+/-30 and 1000+/-200 nm), with differences restricted to the size and
      specific area of the particles. The composites were similar in radiopacity,
      flexural strength, work-of-fracture, and creep. The submicron composite was
      harder but had lower flexural modulus and CC conversion. No significant
      differences in roughness were observed before brushing, although the submicron
      composite had higher gloss. Brushing increased roughness and decreased gloss on
      both materials, but the submicron composite retained higher gloss after brushing.
      SIGNIFICANCE: The monomodal submicron glass filler system demonstrated potential
      for use in restorative dental composites, particularly due to improved esthetic
      properties.

PMID- 24095110
TI  - Telomere length, c-myc and mad-1 expression could represent prognosis markers of
      myelodysplastic syndrome.
AB  - Telomere dysfunction might generate genomic instability leading to the
      progression of myelodysplastic syndromes (MDS) into acute myeloid leukemia (AML).
      We investigated telomere length (TL), telomerase activity (TA) and hTERT, c-myc,
      mad1, and p53 expression in the bone marrow of patients with MDS (n=109), AML
      (n=47) and in controls (n=24). TL was lower in MDS patients than in controls
      (p<0.001) and higher in L-MDS (low, intermediate-1 IPSS, p<0.01) respect H-MDS
      (high, intermediate-2 IPSS, p<0.01) patients. Mad-1 expression was higher in MDS
      patients than in controls (p<0.01), c-myc expression was highest in AML and in H
      MDS patients. Our results show that the telomere dynamics might be useful for
      stratifying patients according to a risk scoring system. 

PMID- 24095111
TI  - The autonomic nervous system: a balancing act.
AB  - The overarching theme of the present chapter is the importance of the interaction
      between brain and body in order to maintain homeostasis - an interaction, rather
      than a mere top-down or reflex regulation, as signals from the organs may
      influence the functioning of the brain. For example, the reflex regulation of
      blood pressure and heart rate is not only subject to modulation by ascending
      information from the body, but also by descending information from several areas
      in hypothalamus and cortex. The central nervous system (CNS) has the capacity to
      control its output via the autonomic nervous system (ANS) using an amazing
      differentiation. For example, not only do the biological clock and prefrontal
      cortex contain neurons which influence the parasympathetic or sympathetic motor
      neurons, they also contain different neurons that project to diverse body
      compartments. In the end this leads to integrated responses whereby visceral
      sensory information reaches higher centers in the CNS via vagal or spinal sensory
      pathways, causing a reaction which takes into account factors such as the time of
      day, the season, the reproductive status, mood. Based on all this information,
      the brain sets the balance of the different parts of the ANS, causing its output
      to change its emphasis according to the situation. A disturbed balance, either as
      a result of behavior or of disease of any of the organs, may lead to pathology
      affecting the functioning of the entire individual. 

PMID- 24095112
TI  - Differential responses of components of the autonomic nervous system.
AB  - This chapter conveys several concepts and points of view about the scientific and
      medical significance of differential alterations in activities of components of
      the autonomic nervous system in stress and disease. The use of terms such as "the
      autonomic nervous system," "autonomic failure," "dysautonomia," and "autonomic
      dysfunction" imply the existence of a single entity; however, the autonomic
      nervous system has functionally and neurochemically distinctive components, which
      are reflected in differential responses to stressors and differential involvement
      in pathophysiologic states. One can conceptualize the autonomic nervous system as
      having at least five components: the sympathetic noradrenergic system, the
      sympathetic cholinergic system, the parasympathetic cholinergic system, the
      sympathetic adrenergic system, and the enteric nervous system. Evidence has
      accumulated for differential noradrenergic vs. adrenergic responses in various
      situations. The largest sympathetic adrenergic system responses are seen when the
      organism encounters stressors that pose a global or metabolic threat. Sympathetic
      noradrenergic system activation dominates the responses to orthostasis, moderate
      exercise, and exposure to cold, whereas sympathetic adrenergic system activation
      dominates those to glucoprivation and emotional distress. There seems to be at
      least as good a justification for the concept of coordinated adrenocortical
      adrenomedullary responses as for coordinated adrenomedullary-sympathoneural
      responses in stress. Fainting reactions involve differential adrenomedullary
      hormonal vs. sympathetic noradrenergic activation. Parkinson disease entails
      relatively selective dysfunction of the sympathetic noradrenergic system, with
      prominent loss of noradrenergic nerves in the heart, yet normal adrenomedullary
      function. Allostatic load links stress with degenerative diseases, and Parkinson
      disease may be a disease of the elderly because of allostatic load. 

PMID- 24095113
TI  - Cotransmission in the autonomic nervous system.
AB  - After some early hints, cotransmission was proposed in 1976 and then "chemical
      coding" later established for sympathetic nerves (noradrenaline/norepinephrine,
      adenosine 5'-triphosphate (ATP), and neuropeptide Y), parasympathetic nerves
      (acetylcholine, ATP, and vasoactive intestinal polypeptide (VIP)), enteric
      nonadrenergic, noncholinergic inhibitory nerves (ATP, nitric oxide, and VIP), and
      sensory-motor nerves (calcitonin gene-related peptide, substance P, and ATP). ATP
      is a primitive signaling molecule that has been retained as a cotransmitter in
      most, if not all, nerve types in both the peripheral and central nervous systems.
      Neuropeptides coreleased with small molecule neurotransmitters in autonomic
      nerves do not usually act as cotransmitters but rather as prejunctional
      neuromodulators or trophic factors. Autonomic cotransmission offers subtle, local
      variation in physiological control mechanisms, rather than the dominance of
      inflexible central control mechanisms envisaged earlier. The variety of
      information imparted by a single neuron then greatly increases the sophistication
      and complexity of local control mechanisms. Cotransmitter composition shows
      considerable plasticity in development and aging, in pathophysiological
      conditions and following trauma or surgery. For example, ATP appears to become a
      more prominent cotransmitter in inflammatory and stress conditions. 

PMID- 24095114
TI  - Sensitization of endocrine organs to anterior pituitary hormones by the autonomic
      nervous system.
AB  - Hormone secretion from endocrine glands constitutes a primary component of
      homeostatic control systems that defend whole body tissue viability and function.
      Endocrine organ secretion is controlled by efferent mechanisms that consist of
      both hormonal and neural elements. Anatomical evidence for dual control has led
      to increased understanding of how autonomic neural activity modulates functional
      sensitivity to hormonal input. The clinical relevance of autonomic-endocrine
      interactions is illustrated by examining functional control of the adrenal cortex
      and the ovary, two tissues that require tropic support from the anterior
      pituitary and receive sympathetic neural input. Extrapituitary mechanisms of
      adrenal cortical control including sympathetic neural activity have been
      implicated in controlling the amplitude of the cortisol awakening response (CAR),
      a diagnostic index of hypothalamic-pituitary-adrenal activity in humans. In
      addition, increases in sympathetic neural tone have been implicated in polycystic
      ovary syndrome (PCOS), a leading cause of female infertility. These examples
      offer strong evidence for the capability of autonomic neural activity to alter
      the functional sensitivity of endocrine glands. This interaction has significant
      clinical relevance and needs to be incorporated into our view in assessing
      endocrine organ function and dysfunction. 

PMID- 24095115
TI  - Central control of autonomic function and involvement in neurodegenerative
      disorders.
AB  - The central autonomic network includes the insular cortex, anterior cingulate
      cortex, amygdala, hypothalamus, periaqueductal gray, parabrachial nucleus,
      nucleus of the solitary tract, ventrolateral reticular formation of the medulla,
      and medullary raphe. These areas: are reciprocally interconnected; receive
      converging visceral and somatosensory information; generate stimulus-specific
      patterns of autonomic, endocrine, and motor responses; and are regulated
      according to the behavioral state, including the sleep-wake cycle. Several
      components of the central autonomic networks are affected in neurodegenerative
      disorders characterized by the presence of intracellular inclusions containing
      alpha-synuclein. These include multiple system atrophy (MSA), characterized by
      accumulation of glial cytoplasmic inclusions, and Lewy body disorders, including
      Parkinson disease (PD), dementia with Lewy bodies, and the so-called "pure"
      autonomic failure. In MSA, involvement of the rostral ventrolateral medulla may
      be primarily responsible for orthostatic hypotension; involvement in the pontine
      micturition area, sacral preganglionic nucleus, and Onuf nucleus is responsible
      for neurogenic bladder; and involvement of the pre-Botzinger complex and
      medullary raphe may contribute to sleep-related respiratory abnormalities. In
      contrast, Lewy body disorders are characterized by early involvement of the
      enteric nervous system and cardiac sympathetic ganglia. The dorsal motor nucleus
      of the vagus is affected both in MSA and at early stages of PD. 

PMID- 24095116
TI  - Interaction between cognition, emotion, and the autonomic nervous system.
AB  - The mind and body are intrinsically and dynamically coupled. Perceptions,
      thoughts and feelings change, and respond to, the state of the body. This chapter
      describes the integration of cognitive and affective processes with the autonomic
      control of bodily arousal, focusing on reciprocal effects of autonomic responses
      on decision making, error detection, memory and emotions. Neuroimaging techniques
      are beginning to detail the neuronal substrates mediating these interactions
      between mental and physiological states, implicating cortical regions
      (specifically insular and cingulate cortices) alongside subcortical (amygdala)
      and brainstem (notably dorsal pons) in these mechanisms. The extent to which
      bodily states influence mental processes is determined in part by "interoceptive
      sensitivity," an index of individual differences in the ability to detect one's
      own bodily sensations. Moreover, the misidentification or misattribution of
      interoceptive responses is implicated in a number of pathologies such as
      depersonalization, schizophrenia, and anxiety. Increasing knowledge of the
      mechanisms of body-mind interactions has wide ranging implications, from decision
      making to empathy, and may serve elucidate potential avenues of intervention for
      stress-sensitive conditions in which psychological, cognitive, and emotional
      factors impact on the expression of physical symptoms. 

PMID- 24095117
TI  - Interoception and autonomic nervous system reflexes thermoregulation.
AB  - Important conceptual changes concerning human thermoregulation have occurred in
      the last decade. While the hypothalamus maintains its central role in sensing
      core temperature and providing connectivity to orchestrate heat loss and cold
      defense autonomic neuronal mechanisms, it is now regarded as one of multiple,
      independent thermoeffector pathways that control core body temperature. Recent
      research in primate central and peripheral thermosensitivity has emphasized the
      importance of temperature-activated transient receptor potential (TRP) channels
      and afferent neuronal pathways from peripheral thermosensors that are activated
      by unique combinations of core and shell temperature. The interoceptive aspects
      of behavioral thermoregulation have been emphasized including the primary
      importance of shell (skin) temperature, the concept of thermal discomfort and the
      important contribution of orbitofrontal, insular, somatosensory, and amygdala
      cortical regions deployed to anticipate and avoid thermal stress. Clinical
      testing of human thermoregulation requires afferent stimuli to activate the
      independent thermoeffector loops while monitoring an efferent response. Patterns
      of sweat gland activation, amount of sweat produced, and areas of anhidrosis
      demonstrated by the thermoregulatory and axon reflex sweat testing provide
      diagnostic information about neurological and medical disorders of the autonomic
      nervous system. 

PMID- 24095118
TI  - Regulation of blood pressure by the arterial baroreflex and autonomic nervous
      system.
AB  - Mean arterial pressure (MAP) is a critical hemodynamic factor. The absence of
      proper regulation of MAP can have important pathophysiological consequences. Low
      MAP can cause inadequate blood flow to organs, syncope, and shock. On the other
      hand, elevated MAP contributes to increased oxygen demand by the heart,
      ventricular remodeling, vascular injury, end organ damage, and stroke. The
      arterial baroreflex system is a key controller of MAP and is a complex system. It
      can be considered in its entirety as an integrative physiological system or in
      terms of its regulated component parts. Those component parts include MAP,
      mechanosensory transduction, afferent pathways, central neural circuits, efferent
      pathways, receptor pharmacology, integration with other key homeostatic inputs,
      molecular biology, and/or other elements. This chapter provides an overview of
      each of these individual components but stresses the importance of the
      integrative nature of this reflex. In addition, this chapter explores common
      measurement techniques for the baroreflex and explores the baroreflex in
      diseases. 

PMID- 24095119
TI  - Cooling, pain, and other feelings from the body in relation to the autonomic
      nervous system.
AB  - The main sensory input to the autonomic nervous system comes from small-diameter
      sensory fibers by way of lamina I neurons in the superficial dorsal horn. This
      pathway supports organotopic homeostatic control of the body's condition, but
      also human feelings from the body, such as temperature, pain, itch, affective
      touch, muscle ache, vascular flush, and so on. The anatomical pathways described
      in this chapter reveal that these feelings are correlates of behavioral
      homeostatic responses needed to maintain the health of the body. These findings
      suggest that bodily feelings provide important measures of the body's condition,
      support emotional well-being and awareness, and can be a significant therapeutic
      avenue. 

PMID- 24095120
TI  - The neurological organization of micturition.
AB  - The role of the lower urinary tract (LUT) is to act as a reservoir for urine at
      low pressures and to empty at appropriate times. In health the bladder becomes
      gradually filled during the storage phase, and afferent pathways convey signals
      of bladder fullness. When deemed to be a socially appropriate time and place,
      there is a switch from the storage phase to the voiding phase. Voiding, which
      involves co-ordinated activity between detrusor contraction and urethral
      sphincter relaxation occurs until the bladder is empty. The level of co-ordinated
      activity is complex, requiring both voluntary and autonomic control. In health,
      the control of LUT activity is achieved at several levels involving the
      peripheral nerves, spinal cord and cerebral cortex. The pathway becomes damaged
      following neurological disease resulting in LUT dysfunction. This chapter
      outlines the neural organization and control of micturition and the consequences
      of neurological disease. 

PMID- 24095121
TI  - The clinical importance of the anti-inflammatory vagovagal reflex.
AB  - Excessive activation of the immune system is prevented by anti-inflammatory
      mediators such as corticosteroids and anti-inflammatory cytokines. Recently, it
      became clear that the brain not only senses peripheral inflammation through vagal
      afferent nerve fibers, but also provides an integrated response dampening the
      immune system through vagal efferents. This so-called anti-inflammatory pathway
      has been introduced as a third system by which the immune system is modulated. In
      sepsis, the anti-inflammatory effect is mediated by modulation of splenic
      macrophages, whereas in the gut, vagal nerve fibers synapse with enteric
      cholinergic neurons interacting with resident intestinal macrophages. In this
      chapter, the preclinical data underscoring the importance of this pathway are
      summarized, and its clinical significance is reviewed. Finally, the current data
      supporting its relevance to human disease and its therapeutic potential will be
      discussed. Insight in the mechanisms underlying these crucial properties will
      lead to better understanding of immune-mediated diseases and ultimately to
      improved anti-inflammatory therapies. 

PMID- 24095122
TI  - The role of the autonomic nervous system in cardiac arrhythmias.
AB  - Autonomic nervous system activity exerts potent and diverse effects on cardiac
      rhythm through elaborate neurocircuitry that is integrated at multiple levels.
      Adrenergic activity such as is associated with mental or physical stress or as a
      reflex response to myocardial ischemia is capable of generating significant
      rhythm abnormalities including ventricular fibrillation, the arrhythmia
      responsible for sudden cardiac death. With respect to the ventricles, vagus nerve
      activity is generally antiarrhythmic as it inhibits the profibrillatory effects
      of sympathetic nerve activation, whereas atrial arrhythmias generally derive from
      heightened levels of both vagus and sympathetic nerve activity. Containment of
      neural influences by pharmacological and electrical targeted neuromodulation is
      being pursued as an antiarrhythmic modality. 

PMID- 24095123
TI  - Exercise and the autonomic nervous system.
AB  - The autonomic nervous system plays a crucial role in the cardiovascular response
      to acute (dynamic) exercise in animals and humans. During exercise, oxygen uptake
      is a function of the triple-product of heart rate and stroke volume (i.e.,
      cardiac output) and arterial-mixed venous oxygen difference (the Fick principle).
      The degree to which each of the variables can increase determines maximal oxygen
      uptake (VO2max). Both "central command" and "the exercise pressor reflex" are
      important in determining the cardiovascular response and the resetting of the
      arterial baroreflex during exercise to precisely match systemic oxygen delivery
      with metabolic demand. In general, patients with autonomic disorders have low
      levels of VO2max, indicating reduced physical fitness and exercise capacity.
      Moreover, the vast majority of the patients have blunted or abnormal
      cardiovascular response to exercise, especially during maximal exercise. There is
      now convincing evidence that some of the protective and therapeutic effects of
      chronic exercise training are related to the impact on the autonomic nervous
      system. Additionally, training induced improvement in vascular function, blood
      volume expansion, cardiac remodeling, insulin resistance and renal-adrenal
      function may also contribute to the protection and treatment of cardiovascular,
      metabolic and autonomic disorders. Exercise training also improves mental health,
      helps to prevent depression, and promotes or maintains positive self-esteem.
      Moderate-intensity exercise at least 30 minutes per day and at least 5 days per
      week is recommended for the vast majority of people. Supervised exercise training
      is preferable to maximize function capacity, and may be particularly important
      for patients with autonomic disorders.

PMID- 24095124
TI  - Autonomic control of bone formation: its clinical relevance.
AB  - Bone remodeling is thought to be regulated by many factors including nutritional
      status, humoral factors, and biomechanical stress. However, the involvement of
      the autonomic nervous system, mainly the sympathetic nervous system (SNS), in the
      modulation of bone remodeling is beginning to receive more attention. Neural
      innervation of bone has been demonstrated. Both experimental and clinical
      evidence has indicated the involvement of autonomic nervous system regulation in
      bone metabolism. The sympathetic neural pathway is so far the only identified
      link between the potent leptin-dependent central control and bone cells. An
      intact autonomic nervous system contributes to the maintenance of healthy bone
      tissue. Conversely, disturbance of the autonomic nervous system could induce
      abnormal bone remodeling. In this chapter, we review current knowledge about the
      role of the autonomic nervous system in abnormal bone formation and its
      association with clinical diseases such as heterotopic ossification, ossification
      of the posterior longitudinal ligament, postmenopausal osteoporosis, adolescent
      idiopathic scoliosis, complex regional pain syndrome, Charcot neuro
      osteoarthropathy, unloading-induced osteoporosis, central or peripheral nervous
      system damage, and depression-induced osteoporosis. Understanding the mechanism
      of sympathetic neural signaling in bone remodeling may shed light on a potential
      treatment avenue for the prevention or reversal of bone loss. 

PMID- 24095125
TI  - The circadian system and the balance of the autonomic nervous system.
AB  - Our biological clock, the suprachiasmatic nucleus (SCN), sets the pace of our
      life: it provides a rhythmic function to our sleep-wake cycle. In order to do so
      properly the SCN synchronizes our physiology to behavioral patterns by directing
      the autonomic and hormonal output of the hypothalamus to the different organs of
      the body that require a different setting - activity or inactivity - during
      particular phases of the day or night. In this chapter we show that this delicate
      balance requires that the SCN should not only provide an output to these organs
      but also be informed about the physiological state of the organs in order to
      adapt its output. This occurs via a hypothalamic neuronal network that provides
      the necessary input to the SCN. We argue that the feedback that the SCN receives
      from its hypothalamic target structures is essential to maintain a balance in our
      physiological functions, which fluctuate during the sleep-wake cycle. We propose
      that this crucial role of the hypothalamus in the homeostatic response is the
      reason why, e.g., in aging or depression, changes in the functioning of the
      biological clock, the SCN, lead to the development of pathology. In addition, if
      this balance is not adequately organized, for example, if the signals of the
      biological clock are violated by being active and eating during the night, as in
      shift work, one will be more susceptible to diseases such as hypertension,
      obesity, diabetes, and metabolic syndrome. 

PMID- 24095126
TI  - Autonomic nervous system control of the cerebral circulation.
AB  - The classic view of cerebrovascular physiology has been that blood flow and
      cerebral metabolism are tightly coupled under the influence of substances, such
      as H(+), adenosine, nitric oxide, and K(+), which ensure a rapid and matched
      supply of blood. In part driven by the use of cerebral blood flow measurements in
      functional brain imaging, it has become clear that astrocytes also play a role in
      modulating functionally associated changes in cerebral blood flow. The concept of
      neural control or neurogenically mediated changes in cerebral blood flow is
      relatively newer, although the presence of such nerves was probably identified
      anatomically more than 500 years ago. The autonomic innervation of the cranial
      circulation has both a sympathetic component that arises predominantly from the
      superior cervical ganglion and a cranial parasympathetic component that traverses
      the pterygopalatine (sphenopalatine) and otic ganglion. Neuropeptide transmitters
      such as neuropeptide Y (NPY), vasoactive intestinal polypeptide (VIP), and
      pituitary adenylate cyclase-activating peptide (PACAP), helodermin, and
      helospectin have each been identified in components of the system. Clinical
      problems such as migraine, cluster headache, and stroke likely involve the
      autonomic innervation of the cerebral circulation in terms of disorder expression
      and ultimately with an eye to novel therapies. 

PMID- 24095127
TI  - Autonomic regulation of kidney function.
AB  - The kidneys play a central role in cardiovascular homeostasis by ensuring a
      balance between the fluid taken in and that lost and excreted during everyday
      activities. This ensures stability of extracellular fluid volume and maintenance
      of normal levels of blood pressure. Renal fluid handling is controlled via neural
      and humoral influences, with the former determining a rapid dynamic response to
      changing intake of sodium whereas the latter cause a slower longer-term
      modulation of sodium and water handling. Activity in the renal sympathetic nerves
      arises from an integration of information from the high and low pressure
      cardiovascular baroreceptors, the somatosensory and visceral systems as well as
      the higher cortical centers. Each sensory system provides varying input to the
      autonomic centers of the hypothalamic and medullary areas of the brain at a level
      appropriate to the activity being performed. In pathophysiological states, such
      as hypertension, heart failure and chronic renal disease, there may be an
      inappropriate sympathoexcitation causing sodium retention which exacerbates the
      disease process. The contribution of the renal sympathetic nerves to these
      cardiovascular diseases is beginning to be appreciated with the demonstration
      that renal denervation of resistant hypertensive patients results in a long-term
      normalization of blood pressure. 

PMID- 24095128
TI  - Autonomic neural control of the airways.
AB  - The airways and lungs are innervated by both sympathetic and parasympathetic
      nerves. Cholinergic parasympathetic innervation is well conserved in the airways
      while the distribution of noncholinergic parasympathetic and adrenergic
      sympathetic nerves varies considerably amongst species. Autonomic nerve function
      is regulated primarily through reflexes initiated upon bronchopulmonary vagal
      afferent nerves. Central regulation of autonomic tone is poorly described but
      some key elements have been defined. 

PMID- 24095129
TI  - Multiple system atrophy.
AB  - Multiple system atrophy (MSA) is a sporadic and fatal alpha-synuclein-linked
      oligodendrogliopathy manifesting with progressive autonomic failure, poorly
      levodopa-responsive parkinsonism, and cerebellar ataxia, in any combination. Here
      we review key aspects of MSA integrating important insights from rapidly emerging
      fields such as genetics, diagnostic work-up including imaging, and translational
      therapies aimed at disease modification. 

PMID- 24095130
TI  - Pure autonomic failure.
AB  - A 1925 report by Bradbury and Eggleston first described patients with extreme
      orthostatic hypotension and a low, steady heart rate. Evidence accumulated over
      the next two decades that patients with orthostatic hypotension include those
      with pure autonomic failure (PAF), characterized by isolated peripheral autonomic
      dysfunction and decreased norepinephrine synthesis; multiple system atrophy (MSA)
      with symptoms of a central Parkinson-like syndrome and normal resting plasma
      norepinephrine; and Parkinson's disease (PD), with lesions in postganglionic
      noradrenergic neurons and signs of autonomic dysfunction. All three disorders are
      classified as alpha-synucleinopathies. Insoluble deposits of alpha-synuclein are
      found in glia in MSA, whereas they take the form of neuronal cytoplasmic
      inclusions called Lewy bodies in PAF and PD. The exact relationship between alpha
      synuclein deposits and the pathology remains undetermined. PAF occurs
      sporadically, and progresses slowly with a relatively good prognosis. However, it
      has been proposed that some cases of PAF may develop a central neurodegenerative
      disorder. Differentiation between PAF, MSA, and PD with autonomic failure can be
      facilitated by a number of biochemical and functional tests and by imaging
      studies. Cardiac sympathetic innervation is generally intact in MSA but decreased
      or absent in Parkinson's disease with autonomic failure and PAF. Treatment of PAF
      is directed at relieving symptoms with nonpharmacological interventions and with
      medications producing volume expansion and vasoconstriction. Future studies
      should focus on determining the factors that lead to central rather than solely
      peripheral neurodegeneration. 

PMID- 24095131
TI  - Autonomic dysfunction in Parkinson disease.
AB  - In Parkinson disease (PD), symptoms and signs of autonomic failure occur
      commonly, especially in cardiovascular, gastrointestinal, and genitourinary
      domains. Most patients with PD have neuroimaging evidence of cardiac sympathetic
      denervation. In PD, orthostatic hypertension (OH) can be an early finding and is
      associated with extracardiac noradrenergic denervation and reduced baroreflex
      cardiovagal and sympathoneural responses. Recognition of autonomic impairment is
      important because symptomatic treatment is frequently effective. 

PMID- 24095132
TI  - Diabetic autonomic neuropathy.
AB  - Autonomic neuropathy, once considered to be the Cinderella of diabetes
      complications, has come of age. The autonomic nervous system innervates the
      entire human body, and is involved in the regulation of every single organ in the
      body. Thus, perturbations in autonomic function account for everything from
      abnormalities in pupillary function to gastroparesis, intestinal dysmotility,
      diabetic diarrhea, genitourinary dysfunction, amongst others. "Know autonomic
      function and one knows the whole of medicine!" It is now becoming apparent that
      before the advent of severe pathological damage to the autonomic nervous system
      there may be an imbalance between the two major arms, namely the sympathetic and
      parasympathetic nerve fibers that innervate the heart and blood vessels,
      resulting in abnormalities in heart rate control and vascular dynamics. Cardiac
      autonomic neuropathy (CAN) has been linked to resting tachycardia, postural
      hypotension, orthostatic bradycardia and orthostatic tachycardia (POTTS),
      exercise intolerance, decreased hypoxia-induced respiratory drive, loss of
      baroreceptor sensitivity, enhanced intraoperative or perioperative cardiovascular
      lability, increased incidence of asymptomatic ischemia, myocardial infarction,
      and decreased rate of survival after myocardial infarction and congestive heart
      failure. Autonomic dysfunction can affect daily activities of individuals with
      diabetes and may invoke potentially life-threatening outcomes. Intensification of
      glycemic control in the presence of autonomic dysfunction (more so if combined
      with peripheral neuropathy) increases the likelihood of sudden death and is a
      caveat for aggressive glycemic control. Advances in technology, built on decades
      of research and clinical testing, now make it possible to objectively identify
      early stages of CAN with the use of careful measurement of time and frequency
      domain analyses of autonomic function. Fifteen studies using different end points
      report prevalence rates of 1% to 90%. CAN may be present at diagnosis, and
      prevalence increases with age, duration of diabetes, obesity, smoking, and poor
      glycemic control. CAN also cosegregates with distal symmetric polyneuropathy,
      microangiopathy, and macroangiopathy. It now appears that autonomic imbalance may
      precede the development of the inflammatory cascade in type 2 diabetes and there
      is a role for central loss of dopaminergic restraint on sympathetic overactivity.
      Restoration of dopaminergic tone suppresses the sympathetic dominance and reduces
      cardiovascular events and mortality by close to 50%. Cinderella's slipper can now
      be worn! 

PMID- 24095133
TI  - Hypoglycemia-associated autonomic failure in diabetes.
AB  - The concept of hypoglycemia-associated autonomic failure (HAAF) in diabetes
      posits that recent antecedent hypoglycemia, as well as sleep or prior exercise,
      causes both defective glucose counterregulation (by attenuating the
      adrenomedullary epinephrine response, in the setting of absent insulin and
      glucagon responses) and hypoglycemia unawareness (by attenuating the
      sympathoadrenal, largely the sympathetic neural, response) and thus a vicious
      cycle of recurrent hypoglycemia. Albeit with different time courses, the
      pathophysiology of defense against hypoglycemia - no decrease in therapeutic
      insulin, no increase in glucagon and an attenuated increase in sympathoadrenal
      activity - is the same in type 1 diabetes and advanced type 2 diabetes.
      Hypoglycemia unawareness is reversible by 2-3 weeks of scrupulous avoidance of
      hypoglycemia in most affected patients. The pathophysiology of HAAF in diabetes
      explains why the incidence of hypoglycemia increases as patients approach the
      absolute endogenous insulin deficient end of the disease, provides a
      comprehensive set of risk factors including those indicative of HAAF, and leads
      logically to the practice of hypoglycemia risk factor reduction. Because of the
      risk of hypoglycemic mortality, presumably from cardiac arrhythmias, glycemic
      goals in diabetes should be individualized, based in part on the risk of
      hypoglycemia. By practicing hypoglycemia risk reduction - addressing the issue,
      applying the principles of aggressive glycemic therapy and considering both the
      conventional risk factors and those indicative of HAAF - it is possible to both
      improve glycemic control and reduce the risk of hypoglycemia in many patients
      with diabetes. 

PMID- 24095134
TI  - Sensory-autonomic interactions in health and disease.
AB  - Although sensory and autonomic nerve fibres generally do not interact directly,
      both may exert influences on blood flow during inflammation. For example, the
      sympathetic neurotransmitter noradrenaline/norepinephrine evokes axon reflexes, a
      response that involves release of vasoactive neuropeptides from the peripheral
      terminals of primary nociceptive afferent fibres. As well as boosting
      inflammation, this mechanism could play a role in normal renal function and heat
      dispersal from the skin. In certain disease states, aberrant communication
      between sensory and autonomic nerves might not only aggravate symptoms but also
      contribute to clinical deterioration by altering local circulatory dynamics. For
      example, in certain forms of neuropathic pain, an aberrant expression of alpha1
      adrenoceptors on primary nociceptive afferents may provide a framework for cross
      talk between sensory and autonomic nerve fibres. In addition to evoking pain and
      other unpleasant symptoms, this cross-talk could aggravate inflammation and
      disrupt nutritive perfusion of affected tissues. Finally, in disorders such as
      cluster headache, intense bursts of trigeminal nociceptive activity may trigger
      trigeminal-parasympathetic vasodilator reflexes which, in turn, provoke secondary
      vascular disturbances that amplify pain. A clearer understanding of sensory
      autonomic interactions both in health and disease may provide a basis for new
      treatment approaches for conditions that respond poorly to conventional
      treatments. 

PMID- 24095135
TI  - Autoimmune autonomic failure.
AB  - Autoimmune autonomic ganglionopathy is a syndrome of panautonomic failure caused
      by antibodies to ganglionic acetylcholine receptors. The clinical syndrome is
      characterized by significant postural hypotension, diffuse cholinergic and
      adrenergic impairment, gastrointestinal dysmotility, urinary retention, and
      pupillary dysfunction. While acute to subacute onset of disease is commonly seen,
      chronic, slowly progressive variants have been described. Serological testing for
      ganglionic acetylcholine receptor antibodies helps confirm the diagnosis. These
      antibodies cause a similar phenotype of autonomic failure in animal models
      indicating that an antibody-mediated functional impairment of ganglionic
      transmission is the underlying etiology. Decrease in antibody levels correlates
      with clinical improvement. Patients may respond to immunomodulatory therapies
      such as prednisone, intravenous immunoglobulin, plasma exchange, and oral
      immunosuppressants. A combination treatment is often required as well as
      symptomatic therapy. 

PMID- 24095136
TI  - The central sympathetic nervous system in hypertension.
AB  - The sympathetic nervous system participates in the development and progression of
      the essential hypertensive state, as shown by increased circulating plasma levels
      of the adrenergic neurotransmitter norepinephrine, elevated norepinephrine
      spillover rate, and augmented sympathetic nerve traffic discharge detected in the
      high blood pressure state. In addition, the sympathetic overdrive participates in
      the development of the metabolic disarray as well as target organ damage
      frequently detected in this condition. The above mentioned sympathetic
      abnormalities explain why adrenergic overdrive represents an important
      therapeutic target in the treatment of hypertension. 

PMID- 24095137
TI  - Pathology of emesis: its autonomic basis.
AB  - Vagal and non-vagal pathways as well as several brainstem nuclei participate in
      vomiting in response to different emetic stimuli. Autonomic pathways involved in
      nausea are less well understood. Numerous gastrointestinal disorders with
      prominent nausea and vomiting including gastroparesis, cyclic vomiting syndrome,
      and motion sickness have associated autonomic nervous system dysfunction.
      Autonomic disturbances are also seen with non-gastrointestinal diseases with gut
      manifestations such as migraine headaches, orthostatic intolerance, and familial
      dysautonomia. Stimulation of emetic pathways involves activation of a range of
      receptor subtypes. Agents acting on these receptors form the basis for antiemetic
      therapies. Chemotherapy-induced nausea and vomiting, a prevalent and severe
      consequence of anticancer treatment, is preventable in many instances by agents
      acting on the autonomic nervous system. Likewise, non-medication therapies may
      act in part via modulation of some of these same autonomic pathways. 

PMID- 24095138
TI  - Sympathetic microneurography.
AB  - The sympathetic nervous system plays important roles in the beat-to-beat control
      of blood pressure, the control of blood flow through various organs and the
      maintenance of core temperature through thermoregulatory processes. The
      development of microneurography, in which nerve activity can be recorded directly
      from intraneural microelectrodes inserted percutaneously into a peripheral nerve
      in awake human subjects, has provided a wealth of information on the control of
      sympathetic outflow to muscle and skin. Although not intended to be diagnostic,
      recordings of muscle sympathetic nerve activity (MSNA) and skin sympathetic nerve
      activity (SSNA) in different disease states have increased our understanding of
      the operation of the sympathetic nervous system. And while quantification of
      sympathetic nerve activity is still largely limited to measures of burst
      frequency (bursts/minute) and burst incidence (bursts/100 heart beats), the
      development of single-unit recordings of MSNA and SSNA have provided more
      detailed information on how the sympathetic nervous system grades its output.
      This chapter reviews the development of sympathetic microneurography and its
      application in health and disease. 

PMID- 24095139
TI  - Sympathetic neuroimaging.
AB  - Sympathetic neuroimaging provides an important supplement to physiological,
      neurochemical, and neuropharmacological approaches in the evaluation of patients
      with clinical autonomic disorders. Almost all sympathetic neuroimaging to date
      has involved visualization of noradrenergic innervation in the left ventricular
      myocardium. Single-photon emission computed tomography (SPECT) scanning after
      injection of the sympathomimetic amine (123)I-metaiodobenzylguanidine ((123)I
      MIBG) constitutes by far the most commonly used means worldwide to assess cardiac
      sympathetic innervation. Based on heart:mediastinum ratios of (123)I-MIBG-derived
      radioactivity, decreased uptake, increased washout, or both have been reported in
      many disorders and relate to diagnosis and prognosis. Cardiac sympathetic
      neuroimaging and postmortem neuropathological findings have linked alpha
      synucleinopathy with noradrenergic denervation in Lewy body diseases. Especially
      because of the utility of cardiac sympathetic neuroimaging in distinguishing
      Parkinson disease from multiple system atrophy in patients with clinical evidence
      of central neurodegeneration and orthostatic hypotension, sympathetic
      neuroimaging seems a valuable addition to physiological, neuropharmacological,
      and neurochemical approaches in the diagnostic evaluation of selected patients
      with autonomic and neurodegenerative disorders. 

PMID- 24095140
TI  - Skin biopsies in the assessment of the autonomic nervous system.
AB  - Cutaneous punch biopsies are widely used to evaluate nociceptive C fibers in
      patients with suspected small-fiber neuropathy. Recent advances in
      immunohistochemical techniques and interest in cutaneous autonomic innervation
      has expanded the role of skin biopsy in the evaluation of the peripheral nervous
      system. The dermal layers of the skin provide a unique window into the structural
      evaluation of the autonomic nervous system. Peripheral adrenergic and cholinergic
      fibers innervate a number of cutaneous structures, such as sweat glands and
      arrector pili muscles, and can easily be seen with punch skin biopsies. Skin
      biopsies allow for both regional sampling, in diseases with patchy distribution,
      and the opportunity for repeated sampling in progressive disorders. The
      structural evaluation of cutaneous autonomic innervation is still in its
      scientific infancy, with a number of different methodologies and techniques that
      will require standardization and widespread acceptance before becoming a standard
      of care. Future studies of autonomic innervation in acquired, hereditary,
      neurodegenerative, or autoimmune disorders will be necessary to determine the
      clinical utility of skin biopsy in these disease states. 

PMID- 24095141
TI  - Heart rate variability.
AB  - Heart rate variability (HRV) provides indirect insight into autonomic nervous
      system tone, and has a well-established role as a marker of cardiovascular risk.
      Recent decades brought an increasing interest in HRV assessment as a diagnostic
      tool in detection of autonomic impairment, and prediction of prognosis in several
      neurological disorders. Both bedside analysis of simple markers of HRV, as well
      as more sophisticated HRV analyses including time, frequency domain and nonlinear
      analysis have been proven to detect early autonomic involvement in several
      neurological disorders. Furthermore, altered HRV parameters were shown to be
      related with cardiovascular risk, including sudden cardiac risk, in patients with
      neurological diseases. This chapter aims to review clinical and prognostic
      application of HRV analysis in diabetes, stroke, multiple sclerosis, muscular
      dystrophies, Parkinson's disease and epilepsy. 

PMID- 24095142
TI  - Chronic activation of the baroreflex and the promise for hypertension therapy.
AB  - Recent technical advances have renewed interest in device-based therapy for the
      treatment of drug-resistant hypertension. Findings from recent clinical trials
      regarding the efficacy of electrical stimulation of the carotid sinus for the
      treatment of resistant hypertension are reviewed here. However, a major goal of
      this article is to summarize experimental studies that have provided a conceptual
      understanding of the mechanisms that account for the long-term blood pressure
      lowering of arterial pressure with baroreflex activation. In so doing, the
      mechanistic insight from these studies may help to identify subsets of this
      heterogeneous population that stand to benefit the most. In this regard, because
      clinical, experimental, and theoretical evidence indicates that the kidneys play
      a dominant role in long-term control of arterial pressure, this article focuses
      on the mechanisms that link baroreflex-induced reductions in central sympathetic
      outflow with increases in renal excretory function that lead to sustained
      reductions in arterial pressure. Despite the encouraging findings from recent
      clinical trials, more basic research and additional clinical trials are needed to
      better define the benefit of baroreflex activation therapy in resistant
      hypertension and in other states of sympathetic activation such as heart failure
      and advanced renal disease. 

PMID- 24095143
TI  - Preface.

PMID- 24095145
TI  - Subcytolytic effects of suilysin on interaction of Streptococcus suis with
      epithelial cells.
AB  - Suilysin is a pore-forming cholesterol-dependent cytolysin secreted by
      Streptococcus suis (S. suis), an important swine and zoonotic pathogen. The role
      of suilysin in S. suis host-cell interaction is still unclear. We found a higher
      adherence and invasion rate of an unencapsulated sly-positive strain in
      comparison to its isogenic sly-negative mutant. Electron microscopy revealed that
      formation of membrane ruffles accompanying invasion of the sly-positive strain
      was abolished in the sly-negative mutant. Inhibition experiments showed that the
      actin cytoskeleton was involved in suilysin-mediated effects. Point-mutation of
      the domain putatively responsible for macropore-formation resulted in abolished
      hemolytic and cytolysin activity, but had no effect on S. suis host cell
      association. Concluding, our results indicate that subcytolytic suilysin promotes
      S. suis association with epithelial cells. 

PMID- 24095146
TI  - Genesis and genetic constellations of swine influenza viruses in Thailand.
AB  - Swine influenza virus (SIV) is one of the most important zoonotic agents and the
      origin of the most recent pandemic virus. Asia is considered to be the epicenter
      for genetic exchanging of influenza A viruses and Southeast Asia including
      Thailand serves as a reservoir to maintain the persistence of the viruses for
      seeding other regions. Therefore, searching for new reassortants in this area has
      been routinely required. Although SIVs in Thailand have been characterized,
      collective information regarding their genetic evolution and gene constellations
      is limited. In this study, whole genomes of 30 SIVs isolated during clinical
      target surveillance plus all available sequences of past and currently
      circulating Thai SIVs were genetically characterized based on their evolutionary
      relationships. All genetic pools of Thai SIVs are comprised of four lineages
      including classical swine (CS), Eurasian swine (EAs), Triple reassortants (TRIG)
      and Seasonal human (Shs). Out of 84 isolates, nine H1N1, six H3N2 and one H1N2
      strains were identified. Gene constellations of SIVs in Thailand are highly
      complex resulting from multiple reassortments among concurrently circulating SIVs
      and temporally introduced foreign genes. Most strains contain gene segments from
      both EAs and CS lineages and appeared transiently. TRIG lineage has been recently
      introduced into Thai SIV gene pools. The existence of EAs and TRIG lineages in
      this region may increase rates of genetic exchange and diversity while Southeast
      Asia is a persistent reservoir for influenza A viruses. Continual monitoring of
      SIV evolution in this region is crucial in searching for the next potential
      pandemic viruses. 

PMID- 24095147
TI  - Inverse association between circulating vitamin D and mortality--dependent on sex
      and cause of death?
AB  - BACKGROUND AND AIMS: In various populations, vitamin D deficiency is associated
      with chronic diseases and mortality. We examined the association between
      concentration of circulating 25-hydroxyvitamin D [25(OH)D], a marker of vitamin D
      status, and all-cause as well as cause-specific mortality. METHODS AND RESULTS:
      The study included 3404 participants of the general adult Swiss population, who
      were recruited between November 1988 and June 1989 and followed-up until the end
      of 2008. Circulating 25(OH)D was measured by protein-bound assay. Cox
      proportional hazards regression was used to examine the association between
      25(OH)D concentration and all-cause and cause-specific mortality adjusting for
      sex, age, season, diet, nationality, blood pressure, and smoking status. Per 10
      ng/mL increase in 25(OH)D concentration, all-cause mortality decreased by 20% (HR
      = 0.83; 95% CI 0.74-0.92). 25(OH)D concentration was inversely associated with
      cardiovascular mortality in women (HR = 0.68, 95% CI 0.46-1.00 per 10 ng/mL
      increase), but not in men (HR = 0.97; 95% CI 0.77-1.23). In contrast, 25(OH)D
      concentration was inversely associated with cancer mortality in men (HR = 0.72,
      95% CI 0.57-0.91 per 10 ng/mL increase), but not in women (HR = 1.14, 95% CI 0.93
      1.39). Multivariate adjustment only slightly modified the 25(OH)D-mortality
      association. CONCLUSION: 25(OH)D was similarly inversely related to all-cause
      mortality in men and women. However, we observed opposite effects in women and
      men with respect to cardiovascular and cancer mortality.

PMID- 24095148
TI  - Left ventricular geometry in obesity: Is it what we expect?
AB  - Obesity is characterized by the disproportionate growth of the components of body
      size, including adipose tissue and lean body mass. Left ventricular (LV)
      hypertrophy often develops, due to the coexistence of hemodynamic (cardiac
      workload) and non-hemodynamic components (including body composition and activity
      of visceral fat). While the hypertrophy of cardiomyocytes is produced by the
      hemodynamic load, through sarcomeric replication, there is a parallel growth of
      non-muscular myocardial components, including interstitial fat infiltration and
      accumulation of triglycerides in the contractile elements, which are thought to
      influence LV geometric pattern. Thus, pure intervention on hemodynamic load is
      unlikely to result in effective reduction of LV hypertrophy in obese. We review
      pathophysiology and prevalence of LV hypertrophy in obesity, with specific
      attention to LV geometric abnormalities and relations with body size. 

PMID- 24095150
TI  - Successful treatment of atelectasis with Dornase alpha in a patient with
      congenital muscular dystrophy.
AB  - A 28-year-old neuromuscular patient chronically treated with nocturnal
      noninvasive ventilation developed pulmonary lobar atelectasis and daytime
      hypoxemia. Twenty four-hour 5L/min oxygen was begun, while mechanical cough
      assist aids were applied for seven days. In the following three days, treatment
      with nebulized Dornase alpha (rhDNase) b.i.d. was tested, without any significant
      improvement. On 11 and 13th days rhDNase was instilled by flexible bronchoscopy.
      A rapid resolution of the atelectasis was observed with relief of hypoxemia,
      without significant side effects. On day 16 the patient was discharged without
      oxygen requirements. In non-intubated neuromuscular patients with atelectasis who
      do not respond successfully to non-invasive treatments intrabronchial
      instillation of rhDNase may safely help to improve airway clearance.

PMID- 24095151
TI  - Modulation of corticomotor excitability after maximal or sustainable-rate
      repetitive finger movement is impaired in Parkinson's disease and is reversed by
      levodopa.
AB  - OBJECTIVES: In healthy subjects, fatiguing exercises induce a period of post
      exercise corticomotor depression (PECD) that is absent in Parkinson's disease
      (PD). Our objective is to determine the time-course of corticomotor excitability
      changes following a 10-s repetitive index finger flexion-extension task performed
      at maximal voluntary rate (MVR) and a slower sustainable rate (MSR) in PD
      patients OFF and ON levodopa. METHODS: In 11 PD patients and 10 healthy age
      matched controls, motor evoked potentials (MEPs) were recorded from the extensor
      indicis proprius (EIP) and first dorsal interosseous (FDI) muscles of the
      dominant arm immediately after the two tasks and at 2-min intervals for 10 min.
      RESULTS: In the OFF condition the PECD was absent in the two test muscles after
      both the MVR and MSR tasks. In the ON condition finger movement kinematics
      improved and a period of PECD comparable to that in controls was present after
      both tasks. CONCLUSION: The absence of PECD in PD subjects off medication
      indicates a persisting increase in corticomotor excitability after non-fatiguing
      repetitive finger movement that is reversed by levodopa. SIGNIFICANCE: Dopamine
      depletion is associated with impaired modulation of corticomotor excitability
      after non-fatiguing repetitive finger movement.

PMID- 24095149
TI  - Correlates of muscle strength in diabetes: The study on the assessment of
      determinants of muscle and bone strength abnormalities in diabetes (SAMBA).
AB  - BACKGROUND AND AIMS: Apart from late motor nerve dysfunction, factors affecting
      muscle strength in diabetes are largely unknown. This study was aimed at
      assessing muscle strength correlates in diabetic subjects encompassing a wide
      range of peripheral nerve function and various degrees of micro and macrovascular
      complications. METHODS AND RESULTS: Four-hundred consecutive patients with type 1
      and 2 diabetes (aged 46.4 +/- 13.9 and 65.8 +/- 10.3 years, respectively) from
      the Study on the Assessment of Determinants of Muscle and Bone Strength
      Abnormalities in Diabetes (SAMBA) were examined for upper and lower body muscle
      isometric maximal voluntary contraction by dynamometry. Univariate and
      multivariate regression analyses were applied to identify strength correlates.
      Isometric force at both the upper and lower limbs was significantly lower in
      subjects with than in those without any complication. At univariate analysis, it
      was strongly associated with age, diabetes duration, physical activity (PA)
      level, cardio-respiratory fitness, anthropometric parameters, surrogate measures
      of complications, and parameters of sensory and autonomic, but not motor (except
      amplitude) neuropathy. Multivariate analysis revealed that upper and lower body
      strength correlated independently with male gender and, inversely, with age,
      autonomic neuropathy score (or individual autonomic function abnormalities), and
      vibration perception threshold, but not sensory-motor neuropathy score. Diabetes
      duration and PA level were excluded from the model. CONCLUSIONS: Both upper and
      lower body muscle strength correlate with measures of diabetic complications and
      particularly with parameters of sensory and especially autonomic nerve function,
      independently of diabetes duration and PA level, thus suggesting the involvement
      of mechanisms other than manifest motor nerve impairment.

PMID- 24095152
TI  - Fascicular thickening of the median nerve detected by sonography in an anterior
      interosseous syndrome as a brachial plexus neuritis.

PMID- 24095153
TI  - Identifying electrode bridging from electrical distance distributions: a survey
      of publicly-available EEG data using a new method.
AB  - OBJECTIVE: EEG topographies may be distorted by electrode bridges, typically
      caused by electrolyte spreading between adjacent electrodes. We therefore sought
      to determine the prevalence of electrode bridging and its potential impact on the
      EEG literature. METHODS: Five publicly-available EEG datasets were evaluated for
      evidence of bridging using a new screening method that employs the temporal
      variance of pairwise difference waveforms (electrical distance). Distinctive
      characteristics of electrical distance frequency distributions were used to
      develop an algorithm to identify electrode bridges in datasets with different
      montages (22-64 channels) and noise properties. RESULTS: The extent of bridging
      varied substantially across datasets: 54% of EEG recording sessions contained an
      electrode bridge, and the mean percentage of bridged electrodes in a montage was
      as high as 18% in one of the datasets. Furthermore, over 40% of the recording
      channels were bridged in 9 of 203 sessions. These findings were independently
      validated by visual inspection. CONCLUSIONS: The new algorithm conveniently,
      efficiently, and reliably identified electrode bridges across different datasets
      and recording conditions. Electrode bridging may constitute a substantial problem
      for some datasets. SIGNIFICANCE: Given the extent of the electrode bridging
      across datasets, this problem may be more widespread than commonly thought.
      However, when used as an automatic screening routine, the new algorithm will
      prevent pitfalls stemming from unrecognized electrode bridges.

PMID- 24095154
TI  - Prognostic value of EEG asymmetries for development of drug-resistance in drug
      naive patients with genetic generalized epilepsies.
AB  - OBJECTIVE: Previous studies based solely on visual EEG analysis reported
      equivocal results regarding an association of pharmaco-resistance with EEG
      asymmetries in genetic generalized epilepsies (GGE). We addressed this issue by
      applying both visual and quantitative methods to the pretreatment EEG of GGE
      patients. METHODS: Socio-demographic/disease characteristics and response to
      treatment/discontinuation trial for these patients were recorded at 6months and
      at last follow up. The first EEG was retrospectively, blindly, and visually
      assessed for focal slowing, focal discharges and also quantitatively analyzed for
      amplitude or latency asymmetries of generalized discharges. Association between
      these variables and development of drug-resistance was evaluated. RESULTS: Out of
      51 subjects, 40% had some type of EEG asymmetry by visual, 37% by quantitative
      and 54% by combined analysis. Drug-resistance was identified in 52% of patients
      after 6months and in 24% at the end of the follow up period (~4.2years). 27% of
      patients underwent a discontinuation trial; 43% unsuccessfully. There was no
      association between baseline EEG asymmetries of any type and refractoriness to
      medical therapy, regardless of analytical method used. CONCLUSIONS: In a
      carefully selected cohort of medication-naive GGE patients, visual and
      quantitative asymmetries in the first EEG were not associated with the
      development of pharmaco-resistance. SIGNIFICANCE: These findings do not provide
      support for utilization of EEG asymmetries as a prognostic tool in GGE.

PMID- 24095155
TI  - Combined cap disease and nemaline myopathy in the same patient caused by an
      autosomal dominant mutation in the TPM3 gene.
AB  - The slow alpha-tropomyosin gene (TPM3) has been associated with three distinct
      histological entities: nemaline myopathy (NM, NEM1), congenital fibre-type
      disproportion (CFTD), and cap disease (CD). Here we describe a patient presenting
      an early-onset congenital myopathy associated with a combination of well
      separated cap structures and nemaline bodies in his muscle biopsy. Exome
      sequencing analysis allowed us to identify a de novo missense mutation in the
      TPM3 gene. Our study confirms the extreme variability of morphological findings
      in TPM3-related myopathies, and proves that cap and nemaline bodies are two sides
      of the same 'coin'. 

PMID- 24095156
TI  - Weight gain during pregnancy in women with gestational diabetes: How little is
      too little?
AB  - We evaluated maternal weight gain in women with gestational diabetes, and
      assessed their compliance with the Institute of Medicine (IOM) weight gain
      targets. Only 28% of women achieved the IOM targets, with 40% gaining inadequate
      weight. Those who gained inadequate weight did not suffer any increase in adverse
      pregnancy outcomes.

PMID- 24095157
TI  - Glycaemic instability correlates with a hyperglucagonaemic response in patients
      with type 1 diabetes without residual beta-cell function.
AB  - We investigated the association between arginine-stimulated glucagon secretion
      (AUCIRG) and several parameters of glycaemic variability in 12 patients with type
      1 diabetes without residual beta-cell function. AUCIRG positively correlated with
      the SD and mean amplitude of glycaemic excursions, thus glucagon might contribute
      to glycaemic instability, independent of endogenous insulin. 

PMID- 24095158
TI  - Association of inflammatory factors with occurrence and recurrence of atrial
      fibrillation: a meta-analysis.
AB  - BACKGROUND: The role of circulating inflammatory factors in atrial fibrillation
      (AF) occurrence and recurrence remains inconclusive. METHODS: We conducted a meta
      analysis of observational studies evaluating the association of inflammatory
      factors with AF risk, postoperative AF (POAF) occurrence after coronary artery
      bypass grafting (CABG) surgery, and AF recurrence after electrical cardioversion
      (EC) or catheter ablation. RESULTS: Increased C-reactive protein (CRP),
      interleukin-6 (IL-6) and tumor necrosis factor-alpha were significantly
      associated with AF risk (standardized mean difference [SMD] [95% confidence
      interval (CI)]: 0.95 [0.72-1.18], 0.89 [0.64-1.15] and 2.20 [1.17-3.23],
      respectively). In subgroup analysis, CRP was significantly associated with
      persistent and permanent AF risk, but not with paroxysmal AF. Increased
      preoperative CRP and IL-6 were associated with greater risk of post-CABG AF (SMD
      [95% CI]: 0.28 [0.02-0.54] and 1.03 [0.03-2.04], respectively). Consistent
      significant associations between CRP and AF recurrence were found in both patient
      subgroups who underwent EC (SMD, 0.56; 95% CI, 0.36-0.76) and ablation (SMD,
      0.48; 95% CI, 0.11-0.86). IL-6 was significantly associated with AF recurrence
      after ablation (SMD, 0.55; 95% CI, 0.25-0.85), but not with the recurrence after
      EC (SMD, 0.85; 95% CI, -0.26-1.95). CONCLUSION: Increased circulating
      inflammatory factors, such as CRP and IL-6, are associated with greater AF risk
      in general population and patients who underwent CABG, as well as with AF
      recurrence after EC or ablation. Future research is warranted to elucidate the
      roles of other inflammatory markers, such as white blood cell, IL-8, and
      transforming growth factor-beta1, in occurrence and recurrence of well
      established different clinical subtypes of AF.

PMID- 24095159
TI  - The resting status of the coronary microcirculation is a predictor of
      microcirculatory function following elective PCI for stable angina.
AB  - BACKGROUND/OBJECTIVES: We performed a prospective study to investigate markers of
      percutaneous coronary intervention (PCI) related microvascular injury. METHODS:
      Consecutive patients undergoing PCI for stable angina were studied. The index of
      microvascular resistance (IMR) was measured using a temperature and pressure
      sensing guidewire (TPSG) before and after single vessel PCI. Basal transit-time
      (TmnBase), that reflected non-hyperemic blood flow was also measured. Fasting
      bloods were taken to measure blood sugar, HbA1c and lipids. Asymmetric
      dimethylarginine (ADMA) was also measured as a marker of systemic endothelial
      function. RESULTS: 55 patients were included in the study. Mean age was 59.9 +/-
      11.2, 74.1% male. There was no significant difference in IMR post PCI compared
      with pre PCI values (IMR pre PCI = 16.96 [11.5,25.38] vs. IMR post PCI 14.2
      [10.37,26.25] p = 0.96). IMR post PCI was higher in diabetic (DM) patients
      compared with non-diabetics [IMR post DM = 22.72 (13.35,42.91) vs. no DM = 13.9
      (10.18,21.45), p = 0.02]. Fasting blood sugar, HbA1c and IMR pre PCI were
      correlated with post PCI IMR. IMR pre PCI, HbA1C and fasting glucose were higher
      in patients who developed PCI related microvascular dysfunction. The strongest
      independent predictor of post PCI IMR was the pre PCI IMR. CONCLUSION: The
      baseline status of the microcirculation is an important determinant of post PCI
      microvascular function. Diabetics appear to have higher post PCI IMR.

PMID- 24095160
TI  - Strategies for the prevention of acute mountain sickness and treatment for large
      groups making a rapid ascent in China.
AB  - Approximately 26.8% of China's land area has an elevation of 3000 m above sea
      level or higher. Because of recent demands for economic development and new
      construction in highland areas, many people have relocated from the plains to
      high plateau regions and have to face the possibility of contracting acute
      mountain sickness. Therefore, prevention and treatment strategies are necessary
      to reduce the incidence of acute mountain sickness in people who rapidly ascend
      to plateau areas. This paper describes the Chinese experience when large numbers
      of people moved to the plateau and the steps that were taken to deal with this
      illness. These steps included implementing basic prevention measures, increasing
      medical awareness among populations ascending to high altitudes, and installing
      standardized medical management systems to prevent and treat acute mountain
      sickness before, during, and after ascent. The incidence of acute mountain
      sickness can be reduced by improving prevention and treatment and by implementing
      the recommendations described in this manuscript.

PMID- 24095161
TI  - Generation, characterization and therapeutic potential of anti-feline TNF-alpha
      MAbs for feline infectious peritonitis.
AB  - Feline infectious peritonitis (FIP) is a lethal infectious disease affecting
      domestic and wild cats. Several reports suggested that TNF-alpha is related to
      the progression of FIP. Thus, the administration of a feline TNF-alpha
      neutralizing antibody to cats with FIP may reduce the disease progression. In
      this study, we have prepared nine monoclonal antibodies (MAbs) that recognize
      feline TNF-alpha. All MAbs neutralized recombinant TNF-alpha. The 50% inhibitory
      concentrations (IC50) of the MAbs for the cytotoxicity of recombinant TNF-alpha
      were 5-684 ng/ml. MAb 2-4 exhibited high neutralizing activity against natural
      TNF-alpha derived from FIPV-infected macrophages, and was confirmed to inhibit
      the following feline TNF-alpha-induced conditions in vitro: (i) an increase in
      the survival rate of neutrophils from cats with FIP, (ii) aminopeptidase N (APN)
      mRNA expression in macrophages, and (iii) apoptosis of a feline T-lymphocyte cell
      line.

PMID- 24095163
TI  - [The smell in the diagnosis of narcolepsy].

PMID- 24095162
TI  - Emerging antigens involved in allergic responses.
AB  - New allergic diseases can 'emerge' because of exposure to a novel antigen,
      because the immune responsiveness of the subject changes, or because of a change
      in the behavior of the population. Novel antigens have entered the environment as
      new pests in the home (e.g., Asian lady beetle or stink bugs), in the diet (e.g.,
      prebiotics or wheat isolates), or because of the spread of a biting arthropod
      (e.g., ticks). Over the last few years, a significant new disease has been
      identified, which has changed the paradigm for food allergy. Bites of the tick,
      Amblyomma americanum, are capable of inducing IgE antibodies to galactose-alpha
      1,3-galactose, which is associated with two novel forms of anaphylaxis. In a
      large area of the southeastern United States, the disease of delayed anaphylaxis
      to mammalian meat is now common. This disease challenges many previous rules
      about food allergy and provides a striking model of an emerging allergic disease.

PMID- 24095164
TI  - [Depression in the elderly: prevalence and associated factors].
AB  - AIM: To determine the prevalence of depression, and to study the factors
      associated with it among community-dwelling 85-year-olds. MATERIAL AND METHODS: A
      cross-sectional study was conducted within the framework of a randomized clinical
      trial in elderly people, all born in 1924, from seven urban and rural primary
      health care centers. Sociodemographic data and geriatric assessment were
      performed. Functional status was measured with Barthel index and Lawton index,
      cognitive impairment with Mini-mental Status Examination, social risk with Gijon
      test, and comorbidity by Charlson index. The presence of exhaustion and physical
      activity were recorded along with the chronic prescription of psycothropic drugs,
      and the presence of depression in clinical registers. Depression was evaluated
      using the Yesavage Geriatric Depression Scale (GDS) of 5 items (depression >= 2).
      The statistical program used was the R project: (version 2.12.2) Foundation for
      Statistical Computing, Vienna. RESULTS: The sample was consisted of 220 subjects,
      129 women (58.6%), 76 (34.5% were depressed using the GDS, 46 (20.9%) subjects
      had depression in the clinical records, and 60 (35.5%) patients were taking
      antidepressant drugs, 66 (36,8%) benzodiazepine, and 10 (4%) antipsychotic drugs.
      Depression was associated with poorer functional status according to basic and
      instrumental activities of daily living, cognitive impairment, exhaustion, low
      physical activity, and psychotropic drugs. Finally, the factors significantly
      associated with depression were low physical activity and increased exhaustion.
      CONCLUSIONS: The present study found a high prevalence of depression in subjects
      older than 85 years. Physical activity and having a good self-perception of
      energy are associated to a lower prevalence of depression.

PMID- 24095165
TI  - [Provision of continuous health care by a unit connected to primary care centres
      coordinated by specialist physicians].
AB  - OBJECTIVE: To evaluate the efficacy and efficiency of a system set up to overcome
      the current disparity between primary and specialist health care and with the
      capacity to detect patients with significant diseases. MATERIAL AND METHODS: To
      describe the activity of the Unit for Connection with Primary Care Centres
      (UCPCC) in the Alcoy Health Area (Alicante) during its first year. RESULTS: A
      total of 450 visits were made, with 6.5 (95% CI 5.7-7.3) first visits, and 3.9
      (95% CI 3.1-4.8) successive ones per day. There were more than 50 reasons for
      consultation, and more than 60 final diagnoses (65.6% non-significant, 14%
      undefined and 12.4% significant). Digestive (31%) and functional (14.4%) diseases
      were the most frequently defined diagnoses, with neoplasic and autoimmune
      diseases among those defined as significant ones. The great majority (86.9%) of
      patients required 1-2 visits, with 40% diagnosed by just reviewing the hospital
      files. More than 20 different complementary examinations were performed, with
      38.8%, 34.4%, 21.6%, and 5.2% of patients requiring 0, 1, 2, or >= 3,
      respectively. Patients with a significant pathology were diagnosed more quickly
      (12.4 +/- 19.4 vs. 45.3 +/- 52.8 days; P = .001), with less complementary
      examinations (0,5 +/- 0,7 vs. 0,9 +/- 0,9 per patient; P = .032. 58.6% vs. 39.6%
      patients without complementary examinations; P = .052), and were more frequently
      referred to specialised medicine (58.6% vs. 18.3%, P < .0001). CONCLUSIONS: The
      demonstrated differential management of patients with potentially significant
      pathology using existing resources, make the UCPCC with internists an efficient
      model for the connection between health care levels.

PMID- 24095166
TI  - [Vaccines and preventive activities in patients with inflammatory arthritis].
AB  - Patients with inflammatory arthritis and eligible for immunosuppressive therapy
      account for more than 1% of general population, and represents a significant
      workload on family doctors. They are prone to other comorbidities, with an
      increased cardiovascular risk and a higher incidence of infections than the
      general population, especially skin infections and pneumonitis. This comorbidity
      can be considered vulnerable to a prevention program-prevention of cardiovascular
      risk, cancer screening, vaccination schedule for adults. As for prevention
      through vaccination, importance should be given to pneumococcal infection -
      significant in adults aged 50 or over, especially amongst immunosuppressed
      patients. The 13-valent conjugate vaccine, which has been recently approved for
      adults, must be considered. An attempt has been made to write a simple,
      applicable document on preventive measures that should be implemented both at
      primary and secondary care level for those adults.

PMID- 24095167
TI  - [Mucosecretor adenocarcinoma of the lung with pleural involvement presenting as a
      pneumothorax. Presentation of a clinical case].
AB  - The combination of a pneumothorax and lung cancer is rare and diagnosis is
      complex. Clinical suspicion of cancer must be based on radiological findings and
      the existence of risk factors. We discuss the mechanisms involved in the
      development of pneumothorax in patients with lung cancer, as well as the clinical
      significance, the recommended diagnostic approach, and therapeutic guidelines. 

PMID- 24095168
TI  - [Palliative care in Primary Care: presentation of a case].
AB  - We present a case of a patient diagnosed with glioblastoma multiforme refractory
      to treatment. Glioblastoma multiforme is the most common primary brain tumour and
      unfortunately the most aggressive, with an estimated mortality of about 90% in
      the first year after diagnosis. In our case the patient had reached a stage of
      life where quality of life was importsnt, with palliative care being the only
      recourse. The family is the mainstay in the provision of care of terminally ill
      patients, and without their active participation it would be difficult to achieve
      the objectives in patient care. We must also consider the family of the
      terminally ill in our care aim, as its members will experience a series of
      changes that will affect multiple areas where we should take action. 

PMID- 24095169
TI  - [Chronic low back pain and abdominal aortic aneurysm].
AB  - Abdominal aortic aneurysm has a population prevalence of 2-5% and mortality in
      case of rupture of 80%. Up to 91% of cases is accompanied with low back pain, so
      it is important to include aortic aneurysm in the differential diagnosis of
      chronic low back pain. Low back pain is one of the most frequent reasons for
      consultions in Services Emergency Hospital Emergency and Primary Care Services,
      with an estimated 80% of population having spinal pain at some point in their
      lives, with 90% of them having a benign course. 

PMID- 24095170
TI  - [Onset of myasthenia gravis in primary care. Presentation of a case].
AB  - Myasthenia gravis is an autoimmune disorder of neuromuscular transmission
      involving the production of autoantibodies directed against skeletal muscle
      receptors, in most cases of acetylcholine. Clinically it is characterized by the
      appearance of muscle weakness after prolonged activity, which tends to recover
      after a period of rest, or administration of acetylcholinesterase inhibitors. It
      is a relatively rare disease, although the prevalence has increased by improved
      diagnosis and increased longevity of the population. The diagnosis can be based
      on evidence after it is suspected using pharmacological, immunological or
      electrophysiology tests. Treatment can be divided into: symptomatic, short term
      and long term. We report the case of a patient who complained of diplopia, this
      muscle weakness being the most common initial symptom of the disease. 

PMID- 24095171
TI  - [Secondary pulmonary embolism to right atrial myxoma].
AB  - A case of pulmonary thromboembolism secondary to atrial myxoma right. The myxoma
      is a primary cardiac tumor, namely, has his origin in the cardiac tissue. Primary
      cardiac tumors are rare, including myxomas, the most common type. Have a
      predilection for females and the most useful tool for diagnosis is
      echocardiography. About 75% of myxomas occur in the left atrium of the heart and
      rest are in the right atrium. Right atrial myxomas in some sometimes associated
      with tricuspid stenosis and atrial fibrillation. The most common clinical
      manifestations include symptoms of this neoplasm constitutional, and embolic
      phenomena resulting from the obstruction to the flow intracavitary. The treatment
      of this condition is surgical. 

PMID- 24095172
TI  - [Epilepsy in the temporal lobe: deja vu in Primary Care].
AB  - Epilepsy is a common disease in the general population. 10% of the population
      will present a seizure throughout his life, although only 1% will have an
      epileptic condition. We can divide the generalized epilepsy and focal. Es in the
      latter that more diagnostic and management difficulties may arise in clinical
      practice, for its wide variety of symptoms and their identification difficult.
      These symptoms may be referred to differently by each patient, often
      dismissively. In focal epilepsy, the most prevalent epilepsy that originates in
      the temporal lobe. The identification and study of this pathology is very
      important because the patient may have episodes of disconnecting means and in one
      third of cases secondarily generalized crises. Although most patients the culprit
      lesion is mesial temporal sclerosis, one must rule out other causes such as
      tumors or infections. 

PMID- 24095173
TI  - [Eosinophilic esophagitis, a pathology on the rise].
AB  - The eosinophilic esofagitis is a pathology that consists of an inflammatory
      condition of the esophagus, which is characterized for having a high percentage
      of eosinophils. It is a problem of allergic origin and his diagnosis is
      increasing in the population, especially in children and adult young persons,
      throughout last decade. The fisiopathology is not completely established
      nowadays. The diagnosis is confirmed with endoscopia and capture of biopsies. The
      differential diagnosis is necessary to be done with the disease for reflux
      gastroesofagico, gastroenteritis eosinofilica, by Crohn's disease, pathology of
      connective fabric, syndrome hipereosinofilico, infections and response of
      hypersensitivity to medicaments. Nowadays there is no a treatment that is
      definitive. We present a clinical case, which was valued initially for the
      consultation of Primary care. 

PMID- 24095174
TI  - Design, preparation, and evaluation of a fixed-orientation antibody/gold
      nanoparticle conjugate as an immunosensing label.
AB  - Herein, we describe the development of a new, highly efficient label for
      immunosensing comprising an antibody/PEGylated gold-nanoparticle (AuNP) conjugate
      in which the antibody molecules are bound to the AuNP surface in a fixed
      orientation. Our method exploits the high density of positive charges on the
      major plane of antibodies that exists when the pH of the solution is lower than
      the isoelectric point of the antibody; the antibody molecules interact with the
      negatively charged AuNP surface through their major plane, enabling the antigen
      binding sites to move freely and therefore to reach maximum accessibility. This
      directed ionic interaction is reinforced by the formation of a peptide bond
      between the amino group of the Lys residues in the antibodies and the carboxylic
      groups of the PEGylated-AuNP surface via EDC chemistry. Electrochemical analyses
      revealed that the fixed-orientation conjugate offers a limit of detection that is
      1 order of magnitude lower than that of a randomly oriented label. The
      performance of the new conjugate as an immunosensing label was assessed for the
      quantitative detection of IgG in human serum. 

PMID- 24095175
TI  - Dietary supplements and medical foods for osteopenia and osteoporosis.
AB  - Dietary supplements, medical foods, and pharmaceutical agents are all used in the
      management of metabolic bone disease. The intended populations, governing
      regulations, safety standards scientific requirements, physician supervision, and
      distribution vary markedly between supplements, medical foods, and drugs. This
      article will review characteristics of dietary supplements and medical foods and
      their use in osteoporosis care. A study that compares the pharmacokinetics of a
      supplement and a medical food containing similar ingredients is used to contrast
      the categories of dietary supplements and medical foods. 

PMID- 24095176
TI  - Induction of cancer cell death by apoptosis and slow release of 5-fluoracil from
      metal-organic frameworks Cu-BTC.
AB  - This study aimed to evaluate the mechanism associated with cytotoxic activity
      displayed by the drug 5-fluorouracil incorporated in Cu-BTC MOF and its slow
      delivery from the Cu-BTC MOF. Structural characterization encompasses elemental
      analysis (CHNS), differential scanning calorimetry (DSC), thermogravimetric
      analysis (TG/DTG), Fournier transform infrared (FIT-IR) and X-ray diffraction
      (XRD) was performed to verify the process of association between the drug 5-FU
      and Cu-BTC MOF. Flow cytometry was done to indicate that apoptosis is the
      mechanism responsible for the cell death. The release profile of the drug 5-FU
      from Cu-BTC MOF for 48 hours was obeisant. Also, the anti-inflammatory activity
      was evaluated by the peritonitis testing and the production of nitric oxide and
      pro-inflammatory cytokines were measured. The chemical characterization of the
      material indicated the presence of drug associated with the coordination network
      in a proportion of 0.82 g 5-FU per 1.0 g of Cu-BTC MOF. The cytotoxic tests were
      carried out against four cell lines: NCI-H292, MCF-7, HT29 and HL60. The Cu-BTC
      MOF associated drug was extremely cytotoxic against the human breast cancer
      adenocarcinoma (MCF-7) cell line and against human acute promyelocytic leukemia
      cells (HL60), cancer cells were killed by apoptosis mechanisms. The drug
      demonstrated a slow release profile where 82% of the drug was released in 48
      hours. The results indicated that the drug incorporated in Cu-BTC MOF decreased
      significantly the number of leukocytes in the peritoneal cavity of rodents as
      well as reduced levels of cytokines and nitric oxide production.

PMID- 24095177
TI  - Economics: the biggest fraud ever perpetrated on the world?

PMID- 24095178
TI  - Addressing invisibility, inferiority, and powerlessness to achieve gains in
      maternal health for ultra-poor women.

PMID- 24095181
TI  - Health care in the USA hanging in the balance.

PMID- 24095180
TI  - [Indications of mesh in surgical treatment of pelvic organ prolapse by vaginal
      route: expert consensus from the French College of Gynecologists and
      Obstetricians (CNGOF)].
AB  - OBJECTIVE: To determine the indications and contraindications concerning
      prosthetic surgery by vaginal route for pelvic organ prolapse. METHODS:
      Literature review and rating of proposals using a formal consensus method.
      RESULTS: Before surgery for genital prolapse, the patient should be counselled
      about the different existing techniques (abdominal and vaginal surgery with and
      without mesh), the reasons why the surgeon offered her the placement of a
      synthetic mesh and also other nonsurgical treatments (pelvic floor rehabilitation
      and pessary). The intervention must be preceded by an assessment of bothersome
      pelvic, urinary, digestive and sexual symptoms. For the surgical treatment of
      cystocele, the use of a synthetic mesh placed by vaginal route is not recommended
      routinely. It should be discussed on a case by case considering the risk/benefit
      ratio. In patients presenting with cystocele recurrence, the placement of a
      synthetic mesh is a reasonable option, in order to reduce the risk of cystocele
      recurrence. With the exception of a few situations (rectocele recurrence), the
      placement of a synthetic mesh is not recommended as first-line therapy for the
      surgical treatment of rectocele by vaginal route. In case of uterine or vaginal
      vault prolapse, repositioning the vaginal vault or uterus using synthetic mesh
      arms is not recommended as first-line surgical therapy. CONCLUSION: Surgeons
      should implement established preventive recommendations that may reduce the risk
      of complications.

PMID- 24095182
TI  - Mental health care in the UK: time for change.

PMID- 24095179
TI  - Characterizing the sexual abuse experiences of young adolescents.
AB  - The purpose of this descriptive study was to: (a) compare the demographics of
      maltreated youth initially labeled as sexually abused by the Department of Child
      and Family Services (DCFS) to maltreated youth classified as sexually abused
      using current and past case records, (b) identify differences in sexual abuse
      experiences and types of perpetrators between boys and girls, and (c) provide a
      detailed description of the sexual abuse experiences for boys and girls.
      Participants were youth ages 9-12 years old with a recent maltreatment
      allegation. The Maltreatment Case Record Abstraction Instrument (MCRAI) was used
      to code child welfare records of 303 maltreated youth of whom 60 experienced
      sexual abuse. Perpetrators were classified by gender into four categories
      (biological parent, parental figure, relative, and unrelated) and type of abuse
      was classified into three categories (penetrative, contact without penetration,
      and non-contact). Using Chi-Square tests, perpetrator categories and sexual abuse
      types were compared by child gender for significant differences. Only 23 (38.3%)
      of the 60 sexually abused youth were labeled as sexually abused in the most
      recent DCFS report when they entered the study. About three-quarters of the
      sexually abused youth experienced non-penetrative physical contact, 40%
      experienced penetration, and 15% experienced sexual abuse without physical
      contact. Most youth (91.7%) were victimized by a male, and 21.7% were abused by a
      female. Youth experienced a large range of sexual abuse experiences, the details
      of which may be important for exploration of consequences of childhood sexual
      abuse. 

PMID- 24095183
TI  - Bringing action on climate and human development together.

PMID- 24095184
TI  - SNAP cuts will harm children in the USA.

PMID- 24095187
TI  - Jeremy Farrar: Wellcome arrival from southeast Asia.

PMID- 24095188
TI  - Micronutrient powders for young children.

PMID- 24095189
TI  - Micronutrient powders for young children.

PMID- 24095190
TI  - Micronutrient powders for young children - Authors' reply.

PMID- 24095191
TI  - Performance indicators and clinical excellence.

PMID- 24095192
TI  - Retraction of the Jikei Heart Study: misquotation of a Comment.

PMID- 24095193
TI  - Should random drugs testing be applied to the medical profession?

PMID- 24095194
TI  - Cell therapy for multiple sclerosis: an evolving concept with implications for
      other neurodegenerative diseases.
AB  - Multiple sclerosis is a major cause of neurological disability, and particularly
      occurs in young adults. It is characterised by conspicuous patches of damage
      throughout the brain and spinal cord, with loss of myelin and myelinating cells
      (oligodendrocytes), and damage to neurons and axons. Multiple sclerosis is
      incurable, but stem-cell therapy might offer valuable therapeutic potential.
      Efforts to develop stem-cell therapies for multiple sclerosis have been
      conventionally built on the principle of direct implantation of cells to replace
      oligodendrocytes, and therefore to regenerate myelin. Recent progress in
      understanding of disease processes in multiple sclerosis include observations
      that spontaneous myelin repair is far more widespread and successful than was
      previously believed, that loss of axons and neurons is more closely associated
      with progressive disability than is myelin loss, and that damage occurs diffusely
      throughout the CNS in grey and white matter, not just in discrete, isolated
      patches or lesions. These findings have introduced new and serious challenges
      that stem-cell therapy needs to overcome; the practical challenges to achieve
      cell replacement alone are difficult enough, but, to be useful, cell therapy for
      multiple sclerosis must achieve substantially more than the replacement of lost
      oligodendrocytes. However, parallel advances in understanding of the reparative
      properties of stem cells--including their distinct immunomodulatory and
      neuroprotective properties, interactions with resident or tissue-based stem
      cells, cell fusion, and neurotrophin elaboration--offer renewed hope for
      development of cell-based therapies. Additionally, these advances suggest avenues
      for translation of this approach not only for multiple sclerosis, but also for
      other common neurological and neurodegenerative diseases.

PMID- 24095196
TI  - Hair repigmentation in melanoma.

PMID- 24095197
TI  - CFTR protein repair therapy in cystic fibrosis.
AB  - Cystic fibrosis is a single gene, autosomal recessive disorder, in which more
      than 1,900 mutations grouped into 6 classes have been described. It is an example
      a disease that could be well placed to benefit from personalised medicine. There
      are currently 2 very different approaches that aim to correct the basic defect:
      gene therapy, aimed at correcting the genetic alteration, and therapy aimed at
      correcting the defect in the CFTR protein. The latter is beginning to show
      promising results, with several molecules under development. Ataluren (PTC124) is
      a molecule designed to make the ribosomes become less sensitive to the premature
      stop codons responsible for class i mutations. Lumacaftor (VX-809) is a CFTR
      corrector directed at class ii mutations, among which Phe508del is the most
      frequent, with encouraging results. Ivacaftor (VX-770) is a potentiator, the only
      one marketed to date, which has shown good efficacy for the class iii mutation
      Gly551Asp in children over the age of 6 and adults. These drugs, or a combination
      of them, are currently undergoing various clinical trials for other less common
      genetic mutations. In the last 5 years, CFTR has been designated as a therapeutic
      target. Ivacaftor is the first drug to treat the basic defect in cystic fibrosis,
      but only provides a response in a small number of patients. New drugs capable of
      restoring the CFTR protein damaged by the most common mutations are required. 

PMID- 24095195
TI  - Allogeneic blood and bone marrow cells for the treatment of severe epidermolysis
      bullosa: repair of the extracellular matrix.
AB  - Contrary to the prevailing professional opinion of the past few decades, recent
      experimental and clinical data support the fact that protein replacement therapy
      by allogeneic blood and marrow transplantation is not limited to freely
      diffusible molecules such as enzymes, but also large structural proteins such as
      collagens. A prime example is the cross-correction of type VII collagen
      deficiency in generalised severe recessive dystrophic epidermolysis bullosa, in
      which blood and marrow transplantation can attenuate the mucocutaneous
      manifestations of the disease and improve patients' quality of life. Although
      allogeneic blood and marrow transplantation can improve the integrity of the skin
      and mucous membranes, today's accomplishments are only the first steps on the
      long pathway to cure. Future strategies will be built on the lessons learned from
      these first transplant studies. 

PMID- 24095198
TI  - Pulmonary artery aneurysm.

PMID- 24095200
TI  - Polychlorinated dibenzo-p-dioxins and dibenzofurans detected in bivalve samples
      from the NOAA National Status and Trends Program.
AB  - Bivalve samples from 142 sites were analyzed to determine the concentration and
      toxicity equivalents (TEQ) of dioxins and furans (D/F) as part of the NOAA
      National Status and Trends Program. The total concentration of 17 D/F ranged from
      not detected to 203 pg/g wet weight of tissue. Octachlorinated dibenzo-p-dioxin,
      OCDD, had a concentration range from not detected to 189 pg/g and a mean
      concentration of 8.65 pg/g. OCDD was the dominant D/F compound detected and
      accounted for, on average, over 70% of the total D/F concentration. The TEQ
      (compared to 2,3,7,8-TCDD) ranged from 0.12 to 7.32 pg TEQ/g. The TEQ for 39% of
      the bivalves analyzed were below 0.238 pg TEQ/g. TEQ above human consumption
      advisory concentration of 1.2 pg TEQ/g were found in 9.3% of the samples
      analyzed. TEQ for D/F indicate very limited human health concerns from
      consumption of bivalves at most of the locations sampled.

PMID- 24095201
TI  - Perfluorinated compounds: levels, trophic web enrichments and human dietary
      intakes in transitional water ecosystems.
AB  - The results of a study on levels of perfluorooctane sulfonate (PFOS) and
      perfluorooctanoic acid (PFOA), analyzed in terms of HPLC-ESI-MS in water,
      sediment, macrophyte, bivalve, crustacean and fish samples, are reported here.
      The aim of the research is to define, for the first time, PFOA/S levels in a
      heavily human-stressed transitional water ecosystem (Orbetello lagoon, Italy) and
      evaluate trophic web enrichments and human dietary intakes. The results obtained
      show that: (i) levels significantly higher than those reported in the literature
      were found in mussels, clams and crabs; (ii) the river is a significant pollution
      source; (iii) although absolute levels are relatively low, macroalgae
      proliferation contributes to redistribute pollutants from river-affected areas
      throughout the entire lagoon basin; (iv) to the best of our current knowledge,
      water-filtering species considered in this study are the most exposed to PFOA/S
      pollution; (v) human daily dietary intakes of PFOA/S through Slow Food-endorsed
      product consumption are below maximum tolerable levels suggested by the EFSA.

PMID- 24095202
TI  - Monitoring mercury in green sea turtles using keratinized carapace fragments
      (scutes).
AB  - The green sea turtles are facing a very high risk of extinction in the wild and
      the impacts of heavy metals contamination contributes with the decline of their
      populations. It is very important to assess noninvasive and nonlethal methods for
      monitoring Hg contamination in sea turtles. Thus, Hg concentrations were measured
      in keratinized fragments (scutes) and internal tissues of green sea turtles from
      the Ceara coast to test the usefulness of scutes as a monitoring subject for sea
      turtles. A significantly positive correlation was found between Hg concentrations
      in muscle and scutes, which demonstrate that scutes can be used as a predictive
      matrix of Hg concentration in muscle tissue of green sea turtles. 

PMID- 24095203
TI  - Effects of varying estuarine conditions on the sorption of phenanthrene to
      sediment particles of Yangtze Estuary.
AB  - The sorption of phenanthrene on the Yangtze Estuary sediment was studied under
      varying conditions of particle size, sediment organic contents, salinity, and
      dissolved organic matter (DOM) concentrations. Small sediment particles showed
      higher trapping capacity for phenanthrene due to the higher organic contents
      associated. The organic carbon-based partition coefficient of phenanthrene to the
      Yangtze Estuary sediment was obtained as 7120 L/kg, lower than the values for
      other soils or sediments reported in previous studies. The magnitude and
      direction of the salt effect were complicated by the specific DOM studied. The
      sediment sorption capacity was greatly increased in saline water in the absence
      of DOM but decreased in the presence of DOM. Given the conditions in the Yangtze
      Estuary, the equilibrium sorption of phenanthrene would be decreased with
      increasing salinity. Overall, the nature and content of both sediment-bound and
      dissolved organic matter dominate the sorption of hydrophobic organic
      contaminants in the estuary.

PMID- 24095199
TI  - Erythro-myeloid progenitors: "definitive" hematopoiesis in the conceptus prior to
      the emergence of hematopoietic stem cells.
AB  - Erythro-myeloid progenitors (EMP) serve as a major source of hematopoiesis in the
      developing conceptus prior to the formation of a permanent blood system. In this
      review, we summarize the current knowledge regarding the emergence, fate, and
      potential of this hematopoietic stem cell (HSC)-independent wave of hematopoietic
      progenitors, focusing on the murine embryo as a model system. A better
      understanding of the temporal and spatial control of hematopoietic emergence in
      the embryo will ultimately improve our ability to derive hematopoietic stem and
      progenitor cells from embryonic stem cells and induced pluripotent stem cells to
      serve therapeutic purposes. 

PMID- 24095204
TI  - Methylmercury in fish from the South China Sea: geographical distribution and
      biomagnification.
AB  - We conducted a large-scale investigation of methylmercury (MeHg) in a total of
      628 marine wild fish covering 46 different species collected from the South China
      Sea between 2008 and 2009. Biological and ecological characteristics such as size
      (length and wet weight), feeding habit, habitat, and stable isotope (delta(15)N)
      were examined to explain MeHg bioaccumulation in marine fish and their
      geographical distribution. MeHg levels in the muscle tissues of the 628
      individuals ranged from 0.010 to 1.811 MUg/g dry wt. Log10MeHg concentration was
      significantly related to their length and wet weight. Feeding habit and habitat
      were the primary factors influencing MeHg bioaccumulation. Demersal fish were
      more likely to be contaminated with MeHg than the epipelagic and mesopelagic
      varieties. Linear relationships were obtained between Log10(MeHg) and delta(15)N
      only for one location, indicating that biomagnification was site-specific.
      Results from this study suggest that dietary preference and trophic structure
      were the main factors affecting MeHg bioaccumulation in marine fish from the
      South China Sea.

PMID- 24095205
TI  - New drugs and targeted treatments in Hodgkin's lymphoma.
AB  - New drugs are being developed in recent years that may change the handling of
      relapsed and refractory Hodgkin's lymphoma patients. Brentuximab vedotin
      treatment has already been approved by the FDA; and other drugs are promising,
      such as histone deacetylase inhibitors, bendamustine, lenalidomide and m-TOR
      inhibitors. 

PMID- 24095206
TI  - Neonatal transfusion.
AB  - Neonates and particularly preterm neonates are frequent recipients of large
      volumes of blood products relative to their size. Good quality evidence for
      transfusion practice in this patient group has been lacking but is now
      increasing. Triggers for red cell transfusion are now better defined, with on
      going trials of platelet transfusions likely to yield similar evidence.
      Transfusion is now extremely safe, but complications such as transfusion
      associated acute lung injury (TRALI) and transfusion associated circulatory
      overload (TACO) are likely to be under recognised, particularly in the sick
      extremely preterm neonate with respiratory symptoms. This review summarises the
      rationale and current practice with regard to blood component therapy. Background
      data on component specifications and hazards of transfusion are provided.
      Indications for transfusion of specific products including red cells, platelets,
      and plasma are discussed, and their use is illustrated by case examples. 

PMID- 24095207
TI  - Exocrine cell-derived microparticles in response to lipopolysaccharide promote
      endocrine dysfunction in cystic fibrosis.
AB  - BACKGROUND: Diabetes in cystic fibrosis (CF) is a result of exocrine pancreas
      alteration followed by endocrine dysfunction at a later stage. Microparticles
      (MPs) are plasma membrane fragments shed from stimulated or damaged cells that
      act as cellular effectors. Our aim was to identify a new form of interaction
      between exocrine and endocrine pancreatic cells mediated by exocrine MPs, in the
      context of recurrent infection in CF. METHODS: MPs from either human exocrine
      CFTRDeltaF508-mutated (CFPAC-1) cells or exocrine normal pancreatic (PANC-1)
      cells were collected after treatment by LPS from Pseudomonas aeruginosa and
      applied to rat endocrine normal insulin-secreting RIN-m5F cells. MP membrane
      integration in target cells was established by confocal microscopy and flow
      cytometry using PKH26 lipid probe. Apoptosis, lysosomal activity, insulin
      secretion were measured after 18 h. MP-mediated NF-kappaB activation was measured
      in HEK-Blue reporter cells by SEAP reporter gene system and in RIN-m5F cells by
      Western blot. In endocrine normal cells, CFTR inhibition was achieved using
      Inhibitor-172. RESULTS: Compared to PANC-1, MPs from CFPAC-1 significantly
      reduced insulin secretion and lysosomal activity in RIN-m5F. MPs induced NF
      kappaB activation by increasing the level of IkappaB phosphorylation. Moreover,
      the inhibition of NF-kappaB activation using specific inhibitors was associated
      with a restored insulin secretion. Interestingly, CFTR inhibition in normal RIN
      m5F cells promoted apoptosis and decreased insulin secretion. CONCLUSIONS: During
      recurrent infections associated with CF, exocrine MPs may contribute to endocrine
      cell dysfunction via NF-kappaB pathways. Membrane CFTR dysfunction is associated
      with decreased insulin secretion.

PMID- 24095208
TI  - Vancomycin concentration in synovial fluid: direct injection into the knee vs.
      intravenous infusion.
AB  - The purpose of this study was to measure joint and serum levels of vancomycin
      following intra-articular (IA) or intravenous (IV) administration, and to compare
      the concentrations achieved in the joint fluid. IA vancomycin was only used to
      treat revision total knee arthroplasty (TKA) due to infection, while IV
      vancomycin was used as a prophylactic agent in primary and revision TKA. Both IA
      and IV vancomycin achieved therapeutic levels in the synovial fluid of the knee,
      but IA delivery of vancomycin resulted in peak levels that were many orders of
      magnitude higher, and also resulted in therapeutic serum levels. The half-life of
      IA-delivered vancomycin was just over three hours, and trough levels remained
      therapeutic in the joint and in serum for 24hours after IA injection. 

PMID- 24095209
TI  - HRCT and MRI of the lung in children with cystic fibrosis: comparison of
      different scoring systems.
AB  - BACKGROUND: Chest imaging is essential in the assessment of respiratory disease
      in cystic fibrosis (CF). High-resolution computed tomography (HRCT) can detect
      progressive lung disease but involves significant delivered dose of ionizing
      radiation. Magnetic resonance imaging (MRI) is radiation-free but is rarely used
      in CF. Based on the limited information on the potential interest of chest MRI in
      CF pediatric patients, the aims of our study were: 1) to evaluate and compare the
      reproducibility of HRCT and MRI scores; and 2) to evaluate the agreement between
      HRCT and MRI scores using both Helbich and Eichinger scores. METHODS: In this
      prospective study, CF children who were having a HRCT for their routine
      assessment were proposed to perform a chest MRI the same day. 17 patients were
      included (median age 12.7 years). Two radiologists scored independently HRCT
      (Helbich score) and MRI (Helbich and Eichinger scores); and established a
      consensus score. Concordance was assessed using the Intraclass Correlation
      Coefficient (ICC); and the inter-observer reproducibility between methods was
      compared using Fisher's Z test for dependent observations. RESULTS: Concordance
      between readers was almost perfect for HRCT score (ICC = 96%) and MRI-Eichinger
      score (84%), and substantial for MRI-Helbich score (68%). Correlation was strong
      between HRCT and MRI (r = 0.86 and 0.91 for HRCT and respectively MRI-Eichinger
      and MRI-Helbich scores) and the concordance almost perfect and substantial (ICC =
      86% and 78% for HRCT and respectively MRI-Eichinger and MRI-Helbich scores).
      CONCLUSIONS: We showed that, in CF children, MRI could adequately visualize lung
      morphologic changes when compared with the "gold-standard" HRCT. Regarding the
      potential cancer risks from associated ionizing radiation with HRCT, these
      results lead us to propose larger intervals of time between two lung HRCTs with
      realization of lung MRI in the meantime.

PMID- 24095210
TI  - One step polymerizing technique for fabricating a hollow obturator.
AB  - PURPOSE: Although a closed hollow obturator is often applied to post maxillectomy
      patients, it has a few problems such as complexity of fabrication and water
      leakage to inside. A one step curing technique to fabricate a closed hollow
      obturator by constructing a small hollow bulb made by two thermoplastic resin
      sheets is described in the present report. METHODS: In the one step curing
      technique, after dewaxing the wax denture fabricated conventionally, one size
      smaller hollow body was fabricated with two thermoplastic resin sheets and set
      into the investment mold as a core. Then the circumferential part of obturator
      was cured by the pour type resin. This technique was used to fabricate an
      obturator prosthesis in a 60-year-old post-maxillectomy patient. The weight of
      this obturator was well controlled and the definitive prosthesis weighed 22 g. At
      a one year follow-up, the obturator fared well without any water leakage or
      breakage. CONCLUSIONS: This technique allows the fabricator to control the
      thickness and weight of the obturator by the amount of relief provided by the
      hollow bulb. It also rectifies the disadvantages of the closed hollow obturator
      such as water leakage and complexity of fabrication.

PMID- 24095211
TI  - Batch fermentative hydrogen production by enriched mixed culture: Combination
      strategy and their microbial composition.
AB  - The effect of individual and combined mixed culture on dark fermentative hydrogen
      production performance was investigated. Mixed cultures from cow dung (C1),
      sewage sludge (C2), and pig slurry (C3) were enriched under strict anaerobic
      conditions at 37 degrees C with glucose as the sole carbon source. Biochemical
      hydrogen production test in peptone-yeast-glucose (PYG) and basal medium was
      performed for individual mixed cultures (C1, C2 and C3) and their combinations
      (C1-C2, C2-C3, C1-C3 and C1-C2-C3) at a glucose concentration of 10 g/L, 37
      degrees C and initial pH 7. Maximum hydrogen yields (HY) of 2.0 and 1.86
      [Formula: see text] by C2, and 1.98 and 1.95 mol(H2)/mol(glucose) by C2-C3 were
      obtained in PYG and basal medium, respectively. Butyrate and acetate were the
      major soluble metabolites produced by all the cultures, and the ratio of butyrate
      to acetate was ~2 fold higher in basal medium than PYG medium, indicating strong
      influence of media formulation on glucose catabolism. The major hydrogen
      producing bacterial strains, observed in all mixed cultures, belonged to
      Clostridium butyricum, C. saccharobutylicum, C. tertium and C. perfringens. The
      hydrogen production performance of the combined mixed culture (C2-C3) was further
      evaluated on beverage wastewater (10 g/L) at pH 7 and 37 degrees C. The results
      showed an HY of 1.92 mol(H2)/mol(glucose-equivalent). Experimental evidence
      suggests that hydrogen fermentation by mixed culture combination could be a novel
      strategy to improve the HY from industrial wastewater.

PMID- 24095212
TI  - Visualizing microbial dechlorination processes in underground ecosystem by
      statistical correlation and network analysis approach.
AB  - Microbial ecosystems are typified by diverse microbial interactions and
      competition. Consequently, the microbial networks and metabolic dynamics of
      bioprocesses catalyzed by these ecosystems are highly complex, and their
      visualization is regarded as essential to bioengineering technology and
      innovation. Here we describe a means of visualizing the variants in a microbial
      community and their metabolic profiles. The approach enables previously
      unidentified bacterial functions in the ecosystems to be elucidated. We
      investigated the anaerobic bioremediation of chlorinated ethene in a soil column
      experiment as a case study. Microbial community and dechlorination profiles in
      the ecosystem were evaluated by denaturing gradient gel electrophoresis (DGGE)
      fingerprinting and gas chromatography, respectively. Dechlorination profiles were
      obtained from changes in dechlorination by microbial community (evaluated by data
      mining methods). Individual microbes were then associated with their
      dechlorination profiles by heterogenous correlation analysis. Our correlation
      based visualization approach enables deduction of the roles and functions of
      bacteria in the dechlorination of chlorinated ethenes. Because it estimates
      functions and relationships between unidentified microbes and metabolites in
      microbial ecosystems, this approach is proposed as a control-logic tool by which
      to understand complex microbial processes.

PMID- 24095213
TI  - Influence of adhesive techniques on fracture resistance of endodontically treated
      premolars with various residual wall thicknesses.
AB  - STATEMENT OF PROBLEM: The choice of restorative method is commonly based on the
      cavity configuration and the residual number of cavity walls. However, the
      residual wall thickness could be a valuable clinical parameter in the choice of
      restoration for endodontically treated teeth. PURPOSE: The fracture resistance of
      endodontically treated premolars was compared with different wall thicknesses
      restored with direct composite resin with and without cuspal coverage and with
      and without fiber post insertion. MATERIAL AND METHODS: This study included 104
      intact human maxillary premolars extracted for periodontal or orthodontic
      reasons. Standardized mesio-occluso-distal cavities were prepared with different
      palatal wall thicknesses (1.5, 2, and 2.5 mm) and a buccal wall thickness of 2
      mm. Teeth were restored with or without a fiber post and with or without cuspal
      coverage. Specimens were subjected to thermocycling (3000 cycles, 5 to 55 degrees
      C) and embedded in polymerized acrylic resin. Teeth were submitted to cyclic
      fatigue followed by a static fatigue test with a universal testing machine; a
      compressive force was applied 30 degrees to the long axis of the teeth until
      fracture. The results were statistically analyzed by 3-way ANOVA (alpha=.05).
      RESULTS: Residual wall thickness (P=.004), the type of adhesive restoration
      (P<.001), and fiber post insertion (P<.001) significantly influenced the fracture
      resistance of endodontically treated premolars. CONCLUSIONS: In specimens with a
      cavity wall thickness >2 mm, direct intracuspal composite resin restorations
      supported by a fiber post achieved comparable fracture resistance. With a
      residual wall thickness <2 mm, only cuspal coverage with or without a fiber post
      provided satisfactory fracture resistance.

PMID- 24095214
TI  - [Resistance to acenocoumarol revealing a missense mutation of the vitamin K
      epoxyde reductase VKORC1: a case report].
AB  - A significant proportion of the interindividual variability of the response to
      vitamin K antagonist (VKA) treatment has been associated with genetic factors.
      Genetic variations affecting the vitamin K epoxide reductase complex subunit 1
      (VKORC1) are associated with hypersensitivity or rarely with resistance to VKA.
      We report the case of a black women patient who presents a resistance to
      acenocoumarol. Despite the use of high doses of acenocoumarol (114 mg/week) for
      the treatment of recurrent pulmonary embolism, the International Normalized Ratio
      was below the therapeutic target. This resistance to acenocoumarol was confirmed
      by the identification of a missense mutation Val66Met of the vitamin K epoxide
      reductase.

PMID- 24095215
TI  - Effect on symptom control of structured information given to patients receiving
      chemotherapy.
AB  - PURPOSE: The performance of a planned education model in patients receiving
      chemotherapy can alleviate the side effects of chemotherapy and thus can increase
      the quality of the patients' lives. In accordance with this view, this study was
      conducted with the purpose of examining the effect of planned education given to
      patients receiving chemotherapy on their symptom control. METHODS: The study was
      quasi-experimental. A sample of 120 patients participated, of which 60 were in
      the experimental group (EG) and 60 were in the control group (CG). A patient data
      form and the chemotherapy symptom assessment scale (C-SAS) were used in order to
      collect the data. Median, Mann-Whitney U test and Wilcoxon signed rank test were
      used to analyze the data. RESULTS: There were statistically significant decreases
      in the frequencies of the following symptoms: nausea, vomiting, constipation,
      pain, infectious signs, problems of mouth and throat, problems of skin and nails,
      appetite changes, weight loss or weight gain, feeling distressed/anxious, feeling
      pessimistic and unhappy, unusual fatigue, difficulty sleeping. Also, there were
      statistically significant decreases in the severity of eleven symptoms and on the
      discomfort levels of nine symptoms. CONCLUSION: In the study, the planned
      education provided by the health-care providers had a positive effect on the
      symptom control of patients receiving chemotherapy.

PMID- 24095216
TI  - Use of electrophysiological monitoring in selective rhizotomy treating
      glossopharyngeal neuralgia.
AB  - The aim of this study was to evaluate the effects of electrophysiological
      monitoring on selective rhizotomy of the glossopharyngeal nerve (SRGN) in
      treatment of glossopharyngeal neuralgia (GPN). From December, 2009 to May, 2012,
      SRGN was carried out on 8 patients with GPN, through a suboccipital sigmoid sinus
      posterior approach. The electrodes were placed on the cricothyroid muscle (vagus
      nerve). Two groups of amplitudes (A1 and A2) were recorded. A1 was recorded when
      the mixed nerve root was stimulated, and A2 when the part of the vagus nerve was
      stimulated. The glossopharyngeal nerve was sectioned and the vagus nerve was
      preserved. If A1/A2 < 50%, the mixed nerve root should be sectioned, otherwise
      the mixed nerve root should be retained. As the representation of vagus nerve,
      the averages of A1 and A2 were 22 and 36 MUV respectively. The 8 patients were
      followed up for 9-39 months. Seven patients (87.5%) obtained complete pain relief
      (excellent) without complications such as hoarseness, dysphagia, and cough. One
      case (12.5%) obtained moderate relief (good), and was under control with
      carbamazepine at a dosage of 600 mg/d. Cough was occurred in this patient, but
      relieved in two months. Electrophysiological monitoring in SRGN can improve the
      efficiency of pain relief and reduce the incidence of complications. 

PMID- 24095217
TI  - Evaluation of overlapped cortical bone area after modified plate fixation with
      bent plate in sagittal split ramus osteotomy.
AB  - PURPOSE: The purpose of this study was to evaluate bony change in an overlapped
      cortical bone area at the anterior site of the proximal segment after modified
      plate fixation with a bent plate in sagittal split ramus osteotomy (SSRO).
      SUBJECTS AND METHODS: The subjects were 66 patients (132 sides) who underwent
      bilateral SSRO setback surgery. After the surgery in SSRO, an overlapped area of
      cortical bone at the anterior site of the proximal segment was not removed to
      keep the contact area between the proximal and distal segments intact, and was
      fixed with a bent plate and 4 screws in each side of the mandible. At the
      posterior site, a 3-7 mm gap was maintained between the proximal and distal
      segments to prevent inward-rotation of the condylar long axis. Ramus width,
      lateral cortex width and lateral cortex step angle were assessed in a coronal
      image immediately after the surgery, and 1-year postoperative by computed
      tomography (CT). RESULTS: Ramus width after 1-year was significantly larger than
      that before surgery and smaller than that immediately after surgery in both sides
      (P < 0.0001). Lateral cortex width after 1-year was significantly larger than the
      preoperative value and smaller than that immediately after surgery in both sides
      (P < 0.0001). Lateral cortex angle after 1-year was significantly larger than the
      preoperative value in both sides (P < 0.0001). CONCLUSION: The above findings
      suggested that the overlapped cortical bone decreased thickness and the cortical
      bone step disappeared following favourable bone remodelling after 1-year, even
      though the cortical bone was not removed at the anterior site of the proximal
      segment.

PMID- 24095218
TI  - Genetic variation in PICALM and Alzheimer's disease risk in Han Chinese.
AB  - The current study was conducted to investigate the association of
      phosphatidylinositol-binding clathrin assembly protein gene (PICALM) with late
      onset Alzheimer's disease (LOAD) risk in Han Chinese. We first sequenced PICALM
      for variants in a small sample (n = 100), and the selected variants were then
      genotyped in a larger cohort (n = 2292). Sequencing analysis identified 16
      variants within PICALM including 5 new variants with extreme low frequency in the
      northern Han Chinese population. However, in the subsequent genotyping, none
      showed a significant association with LOAD risk after Bonferroni correction.
      These findings implicate that PICALM might not play a major role in the genetic
      predisposition to LOAD in Han Chinese.

PMID- 24095219
TI  - Clinical profiles of Parkinson's disease associated with common leucine-rich
      repeat kinase 2 and glucocerebrosidase genetic variants in Chinese individuals.
AB  - Clinical profiles of Parkinson's disease (PD) related to LRRK2 (LRRK2-PD), and
      GBA (GBA-PD) genes have not been reported in Chinese individuals. In this study,
      we have investigated motor and non-motor aspects in 1638 Chinese PD patients who
      carried LRRK2 G2385R or R1628P (LRRK2-PD, n = 223), GBA L444P variant (GBA-PD, n
      = 49), or none of the variants (idiopathic PD [IPD], n = 1366). As a result, age
      at onset and motor and non-motor features of LRRK2-PD patients were similar to
      IPD patients except for milder non-motor symptoms. In contrast, GBA-PD patients
      had a significantly younger age at onset and higher Unified Parkinson's Disease
      Rating Scale scores than LRRK2-PD and IPD patients. In addition, postural
      instability and gait disorders, motor complications, cognitive decline,
      hallucination, sexual dysfunction, and constipation were more frequent in GBA-PD
      than in LRRK2-PD and IPD patients, and GBA-PD patients had a worse performance
      for social functioning and role-emotional scores. Our study represents the first
      large-scale clinical study of LRRK2-PD and GBA-PD in ethnic Chinese individuals.
      The data suggest that both LRRK2-PD and GBA-PD are similar to IPD, except for an
      earlier age at onset and relatively more common non-motor symptoms in GBA-PD
      patients. These findings strengthen our understanding of the clinical
      heterogeneity of PD, and may have implications for molecular classification of
      the disease.

PMID- 24095220
TI  - Treatment effect of capecitabine and docetaxel or docetaxel alone by oestrogen
      receptor status in patients with metastatic breast cancer: results of an
      exploratory analysis.
AB  - We investigated treatment effects by oestrogen receptor (ER) status among women
      with metastatic breast cancer (MBC) receiving capecitabine (C) plus docetaxel (D)
      or D alone in a randomised phase III trial. Data were retrospectively analysed
      from patients whose disease had recurred following (neo)adjuvant anthracyclines.
      ER status was identified in 356/506 patients. In patients with ER-positive
      tumours, median overall survival from enrolment was 17.7 months with CD versus
      12.5 months with D (hazard ratio [HR] 0.65, 95% confidence interval [CI]: 0.47
      0.89; P = 0.007) and median time to progression (TTP) was 6.8 and 5.4 months,
      respectively (HR 0.62, 95% CI: 0.46-0.84; P = 0.002). For patients with ER
      negative tumours, significantly longer TTP was seen with CD (5.2 versus 3.5
      months; HR 0.73, 95% CI: 0.53-0.98; P = 0.038). Whether there is an additional C
      to D treatment benefit in ER-positive versus ER-negative MBC requires further
      evaluation. 

PMID- 24095221
TI  - Renal involvement in a patient with cobalamin A type (cblA) methylmalonic
      aciduria: a 42-year follow-up.
AB  - Chronic renal failure is a well-known long-term complication of methylmalonic
      aciduria (MMA-uria), occurring even under apparently optimal metabolic
      management. The onset of renal dysfunction seems to be dependent on the type of
      defect and vitamin B12-responsiveness. We report on a patient with a vitamin B12
      responsive cobalamin A type (cblA) MMA-uria caused by a homozygous stop mutation
      (p.R145X) in the cobalamin A gene (MMAA). She was diagnosed with chronic kidney
      disease (CKD) stage III at the age of 12 years. Following re-evaluation, the
      patient received vitamin B12 (hydroxocobalamin) treatment, resulting in a
      significant decrease in the concentration of methylmalonic acid (MMA) in urine
      and plasma. Until age 29 years glomerular filtration rate remained stable
      probably due to hydroxocobalamin treatment slowing down progression to end-stage
      renal failure. Kidney biopsies showed non-specific manifestations of chronic
      interstitial inflammation. The patient received a renal transplant at age 35
      years. Under continuous treatment with hydroxocobalamin there is no evidence of
      kidney damage due to MMA-uria until the last follow-up 6 years after
      transplantation. This case report illustrates (i) a long-term follow-up of a
      patient with MMA-uria due to cblA deficiency, (ii) the involvement of the kidney
      as a target organ and (iii) the importance of early and adequate vitamin B12
      substitution in responsive patients. Further investigation will be necessary to
      prove the protective effect of hydroxocobalamin in the kidney in vitamin B12
      responsive patients.

PMID- 24095222
TI  - [Two different airway-management strategies in patients with Launois-Bensaude
      lipomatosis].

PMID- 24095223
TI  - Reply to letter from Stern--problem with modifying Framingham Risk Score.

PMID- 24095224
TI  - Microcontact imprinting of algae on poly(ethylene-co-vinyl alcohol) for biofuel
      cells.
AB  - Hydrogen can be produced using microorganisms (e.g., bacteria and algae); algal
      production has the additional ecological benefit of carbon dioxide fixation. The
      conversion of hydrogen to electricity via fuel cells may be more efficient
      compared to other energy sources of electricity. However, the anode of biofuel
      cells requires the immobilization of microorganisms or enzymes. In this work,
      poly(ethylene-co-vinyl alcohol) (EVAL), was coated on the electrode, and green
      algae was microcontact imprinted onto the EVAL film. The readsorption of algae
      onto algae-imprinted EVAL thin films was compared to determine the ethylene
      content that gave highest imprinting effectiveness and algal binding. Scanning
      electron microscopy and fluorescence spectrometry were employed to characterize
      the surface morphology, recognition capacity, and reusability of the algae
      imprinted cavities. The recognition of an individual algal cell by binding to the
      imprinted cavities was directly observed by video microscopy. Finally, the power
      and current density of the algal biofuel cell using the algae-imprinted EVAL
      coated electrode were measured at about 2-fold higher than electrode sputtered
      platinum on poly(ethylene terephthalate). 

PMID- 24095225
TI  - Review of the evidence: surgical management of 4th and 5th tarsometatarsal joint
      osteoarthritis.
AB  - Osteoarthritis of the lateral tarsometatarsal joints is less common than that
      which is seen in the 1st-3rd tarsometatarsal joints. Despite a suspected increase
      in incidence of tarsometatarsal arthritis and consequently the burden of
      disability and economic impact, guidelines for treatment and decision making
      remain scarce. When conservative treatment fails, lateral column osteoarthritis
      can severely limit a patient's mobility, lifestyle, and present a difficult
      management problem for the foot and ankle specialist. Evidence for the surgical
      techniques used in treatment of lateral column osteoarthritis is limited and
      sporadic within the literature. This article aims to summarise and compare the
      evidence for these surgical management options. This article looks at aetiology
      and epidemiology, with a summary of the biomechanics of the region and a
      comprehensive review of the literature regarding surgical treatment options. 

PMID- 24095226
TI  - A Surgeon's guide to advances in the pharmacological management of acute Charcot
      neuroarthropathy.
AB  - Acute Charcot neuroarthropathy is a devastating condition and, its incidence is
      increasing. Currently, treatment consists of immobilisation and off-loading of
      the involved extremity. Outcomes are frequently poor and novel treatments are
      being sought urgently. This review aims to outline advances in the
      pharmacological treatment of this, condition. PubMed and the Cochrane Database of
      systematic reviews were searched. Relevant papers were cross referenced. Eleven
      original studies were identified. The limited data available suggest pamidronate,
      alendronate and calcitonin provide some clinical and biochemical improvements
      while zoledronic acid is deleterious and, increases off-loading times. However,
      the data is not robust enough to convincingly demonstrate clinically meaningful
      effects. The studies were predominantly low quality and heterogeneous. They
      differed markedly in study type, pharmacological agent used, dosing regimen,
      disease, aetiology/stage/location, concurrent off-loading regimen, outcomes and,
      follow-up. Few were rigorous in controlling for associated confounding variables
      and none investigated long term outcomes. The routine use of pharmacological
      treatment modalities for this condition is not recommended in the United States
      by the Food and Drug Administration or in the United Kingdom by the National
      Institute for Health and Clinical Excellence. Given the evidence available this
      is justified and further higher quality research is required. 

PMID- 24095227
TI  - Comparative study of Lapidus bunionectomy using different osteosynthesis methods.
AB  - The treatment of hallux valgus in patients with pathology of the first
      tarsometatarsal (TMT I) joint by fusion is an established procedure. Multiple
      osteosynthesis methods for the fixation of the TMT I joint are available. In
      comparison to the distal procedures the Lapidus bunionectomy is associated with a
      pseudarthrosis rate of up to 12% [9-11]. We present results after TMT-I
      arthrodesis using an interfragmentary screw and a plantar plate compared with an
      interfragmentary screw and a dorsomedial locking plate. Clinical and radiological
      examinations were performed preoperatively, six weeks and one year
      postoperatively. The AOFAS (American Orthopaedic Foot and Ankle Society) score
      and Visual Analogue Pain Scale (VAS) were evaluated preoperatively and 12 months
      after surgery. We observed a significantly increased rate of undesirable effects
      in mediodorsal plate positioning. 

PMID- 24095228
TI  - Functional results and complication analysis after total ankle replacement: early
      to medium-term results from a Portuguese and Spanish prospective multicentric
      study.
AB  - BACKGROUND: Ankle arthroplasty is increasingly being used to treat end-stage
      ankle osteoarthritis. METHODS: Between January 2005 and January 2011, 159
      patients have been included in an ongoing prospective multicentric study
      analysing the results of total ankle arthroplasty in Portugal and Spain. 119
      patients (119 replacements) were available for review and were evaluated for
      range of motion (ROM), clinical status (American Orthopaedic Foot & Ankle Society
      (AOFAS) ankle-hindfoot score), complications and survivorship rate. RESULTS: Mean
      follow-up was 39 months. A total of 17 complications were reported, with 7
      leading to subsequent surgery (94.1% survivorship rate). Of these, there were two
      infections (98.3% survivorship rate), two painful subtalar arthritis, one
      instability, one malalignment and one tibial bone cyst. Complications not
      requiring further surgery were 6 intra-operative malleolar fractures and 4 cases
      of skin necrosis. CONCLUSIONS: Adequate patient selection and a thorough
      knowledge of the surgical technique are mandatory to reduce the number of
      complications and increase ankle arthroplasty survivorship.

PMID- 24095229
TI  - Total ankle replacement in patients under the age of 50. Should the indications
      be revised?
AB  - BACKGROUND: High physical demand and young age are currently considered
      contraindications for total ankle replacement. This study aimed to compare its
      results between patients under the age of 50 and those aged 50 or older. METHODS:
      103 patients derived from an ongoing prospective multicentric study with a mean
      follow-up of 41 (range, 24-72) months were included in this study. Clinical
      status (AOFAS score), range of motion (ROM), complication and survivorship rates
      were compared between <50 and >=50 patients. RESULTS: ROM and AOFAS score were
      significantly higher, as were their increases relatively to pre-operative values
      in patients <50. Complication and survivorship rates were comparable between both
      groups. CONCLUSIONS: At medium-term, ankle replacement is at least as effective
      in patients under the age of 50 as in those with aged 50 or older. Long-term
      results will allow to assess whether surgical indications for should be revised.

PMID- 24095230
TI  - A comperative study between two different surgical techniques in the treatment of
      late-stage Freiberg's disease.
AB  - BACKGROUND: The aim was to evaluate the results of two different methods in
      surgical treatment for patients with late-stage avascular necrosis of the
      metatarsal head. METHODS: Between 2007 and 2012, fourteen consecutive patients
      (13 females, 1 male; mean age 29 yrs; range, 12-58 yrs) with metatarsal head
      infarction were enrolled for this study. The main presenting symptom was pain on
      walking or daily activities. According to the Smillie classification all of
      lesions were classified as in stage IV-V. Six patients had cheilectomy and
      microfracture procedure in Group A, 8 patients had received cheilectomy and
      dorsal crescentic osteotomy in Group B. Clinical outcomes were evaluated
      according to American Orthopaedic Foot and Ankle Society (AOFAS) lesser toe
      metatarsophalangeal-interphalangeal scale and range of motion (ROM) of
      metatarsophalangeal (MTP) joint. Metatarsal shortening and osteotomy-site healing
      were evaluated with AP and oblique view X-rays. RESULTS: The mean follow-up
      period was 22 months (range, 12-53). The clinical outcomes were excellent in
      11(78%) patients and in the 3(22%) patients the results were good. The AOFAS
      scores increased from a mean of 66.3 points (range, 55-75) preoperatively to 92
      points (range, 84-100) at last follow-up in Group A. The mean AOFAS score
      increased 55.8 points (range, 45-64) to 90.6 points (range, 84-95) in Group B. In
      the patients that osteotomy have been applied there were no limitation of
      movement or fixed deformity of the toe. DISCUSSION: These results suggest that
      both surgical techniques may provide significant improvement in pain and ROM of
      the MTP joint.

PMID- 24095232
TI  - Reliability of Achilles tendon resting angle and calf circumference measurement
      techniques.
AB  - BACKGROUND: The resting angle of the ankle joint may be altered following
      apparently successful management of Achilles tendon rupture. The reliability of
      the Achilles Tendon Resting Angle and Calf Circumference measurements was
      determined. METHODS: Three test-retest measurements for reliability assessment
      were performed on 16 healthy subjects: 10 males and 6 females. RESULTS: The mean
      left Achilles Tendon Resting Angle was mean 50.1 degrees  (range [26-61]), ICC
      0.92 (CI [0.83-0.97]), SEM 2.4 degrees . The mean right Achilles tendon resting
      angle was mean 49.9 degrees  (range [26-60]), ICC 0.91 (CI [0.80-0.96]), SEM 2.6
      degrees . The mean left calf circumference was mean 38.5cm (range [33.3-44.2]),
      ICC 0.97 (CI [0.94-0.98]), SEM 0.6cm, and the mean right calf circumference was
      mean 38.4cm (range [33.3-43.6]), ICC 0.97 (CI [0.94-0.99]), SEM 0.5cm.
      CONCLUSIONS: The Achilles Tendon Resting Angle and Calf Circumference at 15cm
      from the antero-medial joint line had excellent test-retest reliability. These
      are simple, quick and inexpensive measurements, which have the potential to
      correlate with tendon elongation and functional outcome. The Achilles tendon
      resting angle may be used as a guide to tendon length during intra-operative
      repair and rehabilitation.

PMID- 24095231
TI  - Modified Lapidus arthrodesis with plantar plate and compression screw for
      treatment of hallux valgus with hypermobility of the first ray: a preliminary
      report.
AB  - BACKGROUND: TMT-1 arthrodesis is an established method in hallux valgus surgery,
      but it is technically demanding and typically calls for a period of postoperative
      immobilization. METHODS: In this cohort study, initial experience with a plantar
      plate is described. 58 patients (59 arthrodesis) were included. RESULTS: The mean
      duration of protected full weight bearing was 7 weeks. 94.12% patients were
      satisfied with the results, bony union was achieved in 98.31%. The Foot Function
      Index improved by 33 to a mean of 8 (p<.001). The postoperative Mayo Clinic
      Forefoot Score was excellent in 47.04 and good in 47.04%. The mean hallux valgus
      angle improved by 24.4-13.2 degrees  (p<.001). The mean first intermetatarsal
      angle improved by 11.2-5.2 degrees  (p<.001). CONCLUSION: Initial experience with
      this form of fixation appears to provide suitable stability, allow early
      protected weight bearing, with an acceptable level of complications.

PMID- 24095233
TI  - Home therapy pathway - safe and streamlined method of initial management of ankle
      fractures.
AB  - BACKGROUND: Ankle fractures requiring operative fixation often swell up after 24h
      and surgery during this period is not feasible as there are several associated
      risks including infection and wound breakdown. The affected limb is kept elevated
      usually in hospital and once the swelling has sufficiently subsided then the
      operation takes place. We conducted a study looking at the impact of a home
      therapy ankle pathway on the length of stay and safety of patients with ankle
      fractures requiring surgical fixation. METHODS: The length of stay of a control
      group was studied from December 2009 to March 2010. The home therapy ankle
      pathway was then introduced in August 2010. If patients could not have their
      operation within 24h then they were placed in a Plaster of Paris back slab in
      casualty with the ankle reduced, limb care advice given - elevation, cooling and
      DVT thromboprophylaxis - and the patient was discharged home on crutches after a
      slot was determined on the trauma list typically six days later. The patient was
      also given an emergency contact number in case an untoward event occurred, and
      they were called at least once during their home stay by hospital staff to ensure
      all was well. Patients who were unsafe to be discharged on home therapy were
      admitted. This cohort of patients was studied between August 2010 and December
      2011 RESULTS: In the control group, 49 ankle fractures required operative
      intervention. The mean pre-operative length of stay was 2.88 days and the mean
      post op length of stay was 5 days. Between August 2010 and December 2011, after
      implementation of the pathway, 176 ankle fractures requiring operative treatment
      presented to the orthopaedic department. Of these, 105 were eligible for home
      therapy on the ankle pathway prior to surgery. The average pre-operative length
      of stay on the pathway was 0.17 days. The average post op length of stay was 1.72
      days (P<0.001 in all modalities). Home therapy was carried out for an average of
      6.63 days. Challenges of home therapy included persistent swelling and blistering
      (11), loss of reduction (4), poor pain management whilst at home (4) and
      cancellation due to lack of availability of a theatre slot (6). CONCLUSION: With
      patients in whom it is indicated, the home therapy ankle pathway has proved to be
      a safe and resource sparing method of managing ankle fractures prior to surgery.

PMID- 24095234
TI  - The Jones dressing cast for safe aftercare of foot and ankle surgery. A
      modification of the Jones dressing bandage.
AB  - Aftercare of surgical procedures is not consensual in the community of foot and
      ankle surgeons. Although the incidence of infections following foot and ankle
      surgery is rare, soft tissue healing might be jeopardized after extensive and
      multiple approaches. We define a precise fixation technique of the foot and ankle
      in the immediate post-operative phase by what we call "the Jones dressing cast".
      This technique is a modification of the Jones dressing bandage. We compared two
      groups of patients (20 and 23 patients) who underwent similar operative
      reconstructive procedures, with and without the application of the described
      cast, respectively, for one week. At the two-month follow-up, we observed that
      the group, which was treated with the cast required less analgetics, had a
      reduced hospitalization time and achieved faster autonomy using crutches. It may
      be assumed that reduced strain to the soft tissue around the foot due to the cast
      may reduce the complications in the post-operative period. 

PMID- 24095235
TI  - A novel repair method for the treatment of acute Achilles tendon rupture with
      minimally invasive approach using button implant: a biomechanical study.
AB  - BACKGROUND: Minimally invasive Q3 repair has been proposed for acute Achilles
      tendon rupture with low rate of complications. However there are still
      controversies about optimal technique. In this study we aimed to describe
      Endobutton-assisted modified Bunnell configuration as a new Achilles tendon
      repair technique and evaluate its biomechanical properties comparing with native
      tendon and Krackow technique. METHODS: 27 ovine Achilles tendons were obtained
      and randomly placed into 3 groups with 9 specimens ineach. The Achilles tendons
      were repaired with Endobutton-assisted modified Bunnell technique in group 1,
      Krackow suture technique in group 2 and group 3 was defined as the control group
      including native tendons. Unidirectional tensile loading to failure was performed
      at 25mm/min. Biomechanicalproperties such as peak force to failure (N), stress at
      peak (MPa), elongation at failure, and Young'smodulus (GPa) was measured for each
      group. All groups were compared with each other using one-wayANOVA followed by
      the Tukey HSD multiple comparison test (a=0.05). RESULTS: The average peak force
      (N) to failure of group 1 and group 2 and control group was 415.6+/-57.6, 268.1+/
      65.2 and 704.5+/-85.8, respectively. There was no statistically significant
      difference between native tendon and group 1 for the amount elongation at failure
      (p>0.05). CONCLUSIONS: Regarding the results, we concluded that Endobutton
      assisted modified Bunnell technique provides stronger fixation than conventional
      techniques. It may allow early range of motion and can be easily applied in
      minimally invasive and percutaneous methods particularly for cases with poor
      quality tendon at the distal part of rupture. LEVEL OF EVIDENCE: Level II,
      Biomechanical research study.

PMID- 24095236
TI  - Biomechanical analysis of endobutton versus screw fixation after Lisfranc
      ligament complex sectioning.
AB  - BACKGROUND: Our goal was to compare diastasis after endobutton and screw fixation
      after Lisfranc ligament complex sectioning. METHODS: Twenty-four (12 pairs) fresh
      frozen cadaveric feet were assigned to endobutton or screw fixation and loaded to
      343N. Displacement (first-second metatarsal bases) was measured in intact feet
      and after ligament sectioning (Lisfranc, medial-intermediate cuneiform
      ligaments), fixation, and 10,000 cycles. RESULTS: The mean change in diastasis
      for endobutton and screw fixation under initial loading was 1.0mm (95% CI, 0.2
      1.9mm) and 0.0mm (95% CI, -0.4 to 0.4mm), respectively (p=0.017). After cyclic
      loading, diastasis decreased (mean, -0.7mm, 95% CI, -1.2 to -0.1mm) in the
      endobutton group but was unchanged in the screw group (p=0.035). CONCLUSIONS:
      Diastasis after endobutton fixation was significantly greater than after screw
      fixation under initial loading but did not increase further after cyclic loading.

PMID- 24095237
TI  - The role of arthroscopy in the treatment of functional instability of the ankle.
AB  - BACKGROUND: Ankle sprains are common, the majority resolving with functional
      rehabilitation. Some patients are left with symptoms of functional instability
      (FI). Ankle arthroscopy in those with symptoms of FI is not well covered in the
      literature. Our aim was to assess its role in FI of the ankle. METHODS:
      Retrospective case note analysis of patients with FI following an ankle sprain
      from 2005 to 2007. All underwent arthroscopy, provided mechanical instability was
      excluded (EUA and stress X-rays), and there were no signs of soft tissue
      impingement. These patients had exhausted all options of conservative therapy.
      RESULTS: Seventy-seven patients with a mean age of 38.1: five had true mechanical
      instability and were excluded. 72 underwent arthroscopy: 67 (93.1%) had
      significant amounts of scar tissue needing debridement, most commonly in the
      antero-lateral corner (58.3%). 52 patients improved (72.2%) at a minimum of 6
      months follow-up. CONCLUSION: Our study supports the role of ankle arthroscopy in
      the treatment of FI following trauma. It should be considered when conservative
      measures have failed.

PMID- 24095238
TI  - Proximal opening-wedge osteotomy of the first metatarsal for moderate and severe
      hallux valgus using low profile plates.
AB  - BACKGROUND: To present the results of the treatment of hallux valgus with the
      proximal metatarsal opening wedge (PMOW) osteotomy using two different screw and
      plate systems. METHODS: Forty-one patients with moderate and severe hallux valgus
      were treated with the PMOW osteotomy between 2005 and 2009. The fixation was
      obtained by the Darco((r)) BOW or by the Arthrex((r)) LPS plate. Biplanar chevron
      and/or Akin osteotomy were associated according to the magnitude of distal
      angles. Each patient was evaluated with weight-bearing radiographs and AOFAS
      score. RESULTS: The HV, IM, DMA and IP angles improved by a mean of 14 degrees ,
      8 degrees , 11 degrees , 7 degrees  respectively. The sesamoid position improved
      in 79% of the feet. AOFAS score improved from a mean of 50 to 82. CONCLUSION: The
      PMOW osteotomy is effective to correct high-level hallux valgus deformities. Both
      systems guarantee the stability and correction of the osteotomy site. The
      combination with distal procedures is advisable to correct distal angles.

PMID- 24095239
TI  - The optimal injection technique for the osteoarthritic ankle: a randomized, cross
      over trial.
AB  - BACKGROUND: To optimize the injection technique for the osteoarthritic ankle in
      order to enhance the effect of intra-articular injections and minimize adverse
      events. METHODS: Randomized cross-over trial. Comparing two injection techniques
      in patients with symptomatic ankle osteoarthritis. Patients received an injection
      with hyaluronic acid using either one of the techniques. Four weeks later the
      second injection was given using the other technique. Primary outcome was the
      failure rate of the injection. RESULTS: Seventy patients fulfilled the study. The
      failure rate for both injection techniques was 24%. Forty-one patients in the
      traction group and thirty-nine in the group without traction experienced
      treatment related local adverse events. Other secondary outcomes did not show any
      difference between injection techniques. CONCLUSIONS: There is no significant
      difference comparing the two injection methods regarding any of our formulated
      outcome measures. The use of contrast aided fluoroscopy for injecting the severe
      osteoarthritic ankle can be advised at all times.

PMID- 24095240
TI  - Spontaneous peri-talar dislocation after steroid intra-articular injections: a
      case report.
AB  - We report a case of spontaneous peri-talar dislocation after intra-articular
      steroid injections. We have reviewed the literature on spontaneous peri- and sub
      talar dislocations and the effects of intra-articular steroid injections. 

PMID- 24095241
TI  - Response to 're: ankle replacement revision'.

PMID- 24095242
TI  - Re: ankle replacement revision [Foot Ankle Surg 2013;19(2):69].

PMID- 24095243
TI  - Re: bipartite talus: a case series and algorithm for treatment [Foot Ankle Surg
      2013;19(2):96-102].

PMID- 24095244
TI  - Response to 'Bipartite talus - a probably underreported skeletal variation'.

PMID- 24095245
TI  - Tobacco, alcohol and cannabis use during pregnancy: clustering of risks.
AB  - BACKGROUND: Antenatal substance use poses significant risks to the unborn child.
      We examined use of tobacco, alcohol and cannabis among pregnant Aboriginal and
      Torres Strait Islander women; and compared characteristics of women by the number
      of substances reported. METHODS: A cross-sectional survey with 257 pregnant
      Indigenous women attending antenatal services in two states of Australia. Women
      self-reported tobacco, alcohol and cannabis use (current use, ever use, changes
      during pregnancy); age of initiation of each substance; demographic and obstetric
      characteristics. RESULTS: Nearly half the women (120; 47% (95%CI:40%, 53%)
      reported no current substance use; 119 reported current tobacco (46%; 95%CI:40%,
      53%), 53 (21%; 95%CI:16%, 26%) current alcohol and 38 (15%; 95%CI:11%, 20%)
      current cannabis use. Among 148 women smoking tobacco at the beginning of
      pregnancy, 29 (20%; 95%CI:14%, 27%) reported quitting; with 80 of 133 (60%;
      95%CI:51%, 69%) women quitting alcohol and 25 of 63 (40%; 95%CI:28%, 53%) women
      quitting cannabis. Among 137 women reporting current substance use, 77 (56%;
      95%CI:47%, 65%) reported one and 60 (44%; 95%CI:35%, 53%) reported two or three.
      Women using any one substance were significantly more likely to also use others.
      Factors independently associated with current use of multiple substances were
      years of schooling and age of initiating tobacco. CONCLUSIONS: While many women
      discontinue substance use when becoming pregnant, there is clustering of risk
      among a small group of disadvantaged women. Programmes should address risks
      holistically within the social realities of women's lives rather than focusing on
      individual tobacco smoking. Preventing uptake of substance use is critical.

PMID- 24095246
TI  - Effects of tolcapone on working memory and brain activity in abstinent smokers: a
      proof-of-concept study.
AB  - BACKGROUND: Dopamine levels in the prefrontal cortex (PFC) are thought to play an
      important role in cognitive function and nicotine dependence. The catechol-O
      methyltransferase (COMT) inhibitor tolcapone, an FDA-approved treatment for
      Parkinson's disease, increases prefrontal dopamine levels, with cognitive
      benefits that may vary by COMT genotype. We tested whether tolcapone alters
      working memory-related brain activity and performance in abstinent smokers.
      METHODS: In this double-blind crossover study, 20 smokers completed 8 days of
      treatment with tolcapone and placebo. In both medication periods, smokers
      completed blood oxygen level-dependent (BOLD) fMRI scans while performing a
      working memory N-back task after 24h of abstinence. Smokers were genotyped
      prospectively for the COMT val(158)met polymorphism for exploratory analysis.
      RESULTS: Compared to placebo, tolcapone modestly improved accuracy (p=0.017) and
      enhanced suppression of activation in the ventromedial prefrontal cortex (vmPFC)
      (p=0.002). There were no effects of medication in other a priori regions of
      interest (dorsolateral PFC, dorsal cingulate/medial prefrontal cortex, or
      posterior cingulate cortex). Exploratory analyses suggested that tolcapone led to
      a decrease in BOLD signal in several regions among smokers with val/val
      genotypes, but increased or remained unchanged among met allele carriers.
      Tolcapone did not attenuate craving, mood, or withdrawal symptoms compared to
      placebo. CONCLUSIONS: Data from this proof-of-concept study do not provide strong
      support for further evaluation of COMT inhibitors as smoking cessation aids.

PMID- 24095247
TI  - Setipiprant, a selective oral antagonist of human CRTH2: relative bioavailability
      of a capsule and a tablet formulation in healthy female and male subjects.
AB  - BACKGROUND: CRTH2 is a prostaglandin D2 receptor that plays an important role in
      allergic inflammation. Setipiprant is a potent CRTH2 antagonist under development
      for the treatment of allergic diseases. OBJECTIVE: The aim of this study was to
      evaluate the tolerability and pharmacokinetics of a single oral dose of a
      setipiprant capsule (reference) and a tablet formulation. METHODS: This was an
      open-label, 2-period, 2-way crossover, randomized study in which 20 healthy women
      and men (1:1 ratio) received either 2 250-mg capsules or a 500-mg tablet of
      setipiprant. Subjects were between 18 and 45 years old, with a body mass index of
      18.0 to 28.0 kg/m(2). Differences in pharmacokinetics of setipiprant formulations
      were explored overall and by sex. RESULTS: All subjects completed the study. Both
      formulations were well tolerated, with headache the most frequently reported
      adverse event (25% of subjects), followed by flatulence (15%) and somnolence and
      fatigue (10%). The adverse event profile in men and women and between
      formulations was similar. The ratios of geometric means for Cmax (0.94; 95% CI,
      0.79-1.12) and AUC0-infinity (1.01; 95% CI, 0.92-1.12) were mostly within the
      limits of 0.80 to 1.25. When corrected for weight, the differences observed
      between sexes, within each treatment, for Cmax (capsules: 1.01; 95% CI, 0.71
      1.44; tablet: 0.89; 95% CI, 0.62-1.26) and AUC0-infinity (capsules: 1.12; 95% CI,
      0.86-1.47; tablet: 0.96; 95% CI, 0.73-1.25) were minor. CONCLUSION: Both the
      setipiprant formulations were well tolerated. Setipiprant pharmacokinetics were
      similar between formulations, overall, and between sexes. The new tablet
      formulation may constitute a valid alternative to the capsule formulation for
      later clinical development phases. ClinicalTrials.gov identifier: NCT01877629.

PMID- 24095248
TI  - Statins and cognition: a systematic review and meta-analysis of short- and long
      term cognitive effects.
AB  - OBJECTIVE: To evaluate the effect of statins on short-term cognitive function and
      the long-term incidence of dementia. PATIENTS AND METHODS: A systematic search
      was performed of MEDLINE, EMBASE, and the Cochrane Central Register from their
      inception to April 25, 2013. Adults with no history of cognitive dysfunction
      treated with statins were included from high-quality randomized controlled trials
      and prospective cohort studies after formal bias assessment. RESULTS: Sixteen
      studies were included in qualitative synthesis and 11 in quantitative synthesis.
      Short-term trials did not show a consistent effect of statin therapy on cognitive
      end points. Digit Symbol Substitution Testing (a well-validated measure of
      cognitive function) was the most common short-term end point, with no significant
      differences in the mean change from baseline to follow-up between the statin and
      placebo groups (mean change, 1.65; 95% CI, -0.03 to 3.32; 296 total exposures in
      3 trials). Long-term cognition studies included 23,443 patients with a mean
      exposure duration of 3 to 24.9 years. Three studies found no association between
      statin use and incident dementia, and 5 found a favorable effect. Pooled results
      revealed a 29% reduction in incident dementia in statin-treated patients (hazard
      ratio, 0.71; 95% CI, 0.61-0.82). CONCLUSION: In patients without baseline
      cognitive dysfunction, short-term data are most compatible with no adverse effect
      of statins on cognition, and long-term data may support a beneficial role for
      statins in the prevention of dementia.

PMID- 24095249
TI  - A pH-responsive hybrid fluorescent nanoprober for real time cell labeling and
      endocytosis tracking.
AB  - Hydrophilic, fluorescent hybrid nanoprobes (NDI@HNPs) encapsulated with the
      hydrophobic pH-responsive fluorophore (N,N'-di-n-dodecyl-2,6-di(4-methyl
      piperazin-1-yl)naphthalene-1,4,5,8-tetracarboxylic acid diimide, NDI) for
      recognizing and mapping the route of cell phagocytosis have been fabricated based
      on the self-assembly of amphiphilic diblock copolymer PS-b-PAA and the subsequent
      shell cross-linking with 3-mercaptopropyltrimethoxy silane (MPTMS). The as
      synthesized NDI@HNPs has a typical spherical morphology of 46 nm in diameter with
      excellent monodispersity in aqueous solution. The NDI@HNPs probe exhibits
      extremely low cytotoxicity, fast real time pH response and enhanced fluorescence
      intensity under acidic environment with respect to the corresponding free dye in
      highly polar aqueous system because of the encapsulation of NDI molecules inside
      nanoparticle cores with weak polarity environment. The fluorescence intensity of
      NDI@HNPs is enhanced by 55-fold upon changing from neutral (pH = 7.4) or basic
      (pH = 8.4) to acid (pH = 3.4) in aqueous system, in contrast to the serious
      fluorescence quenching of free NDI in the same medium, which can exactly meet the
      physiological pH range in cells. The favorably long emission wavelength is
      beneficial to the low scattering and minimal interfering requirements to
      fluorescent bioimaging. Moreover, functionalization with rapid cell-penetrating
      peptides (HIV-1 TAT) allows them to overcome the physiological and biological
      barriers during the phagocytosis process. Its characteristic fluorescent response
      to pH benefits the intracellular labeling and organelle targeting, realizing the
      real time tracking of the probe entry into cancer cells, the accumulation into
      the endolysosome and the further escape.

PMID- 24095250
TI  - Thermosensitive hydrogels based on polypeptides for localized and sustained
      delivery of anticancer drugs.
AB  - Thermosensitive hydrogels based on poly(gamma-ethyl-L-glutamate)-poly(ethylene
      glycol)-poly(gamma-ethyl-L-glutamate) triblock copolymers (PELG-PEG-PELG) were
      prepared for localized and sustained delivery of anticancer drugs. The
      polypeptide-based hydrogels showed much lower critical gelation concentration
      than the traditional polyester-based hydrogels. In vivo biocompatibility studies
      revealed that the in situ formed gels in the subcutaneous layer last for ~ 21
      days, and H&E staining study suggested acceptable biocompatibility of our
      materials in vivo. Then the hydrogels were tried as injectable implants to
      encapsulate antitumor drug, paclitaxel (PTX), to assess the in situ anti-tumoral
      activity using liver cancer xenograft model. The results demonstrated that the
      PTX-incorporated hydrogels could efficiently suppress the tumor growth, and did
      not result in obvious damage to normal organs. Therefore, the polypeptide-based
      thermosensitive hydrogels designed in the present study have great potential to
      serve as an effective platform for localized anti-cancer drug delivery.

PMID- 24095251
TI  - Enhanced osteoporotic bone regeneration by strontium-substituted calcium silicate
      bioactive ceramics.
AB  - The regeneration capacity of the osteoporotic bones is generally lower than that
      of the normal bones. Current methods of bone defect treatment for osteoporosis
      are not always satisfactory. Recent studies have shown that the silicate based
      biomaterials can stimulate osteogenesis and angiogenesis due to the silicon (Si)
      ions released from the materials, and enhance bone regeneration in vivo. Other
      studies showed that strontium (Sr) plays a distinct role on inhibiting bone
      resorption. Based on the hypothesis that the combination of Si and Sr may have
      synergetic effects on osteoporotic bone regeneration, the porous Sr-substituted
      calcium silicate (SrCS) ceramic scaffolds combining the functions of Sr and Si
      elements were developed with the goals to promote osteoporotic bone defect
      repair. The effects of the ionic extract from SrCS on osteogenic differentiation
      of bone marrow mesenchymal stem cells derived from ovariectomized rats (rBMSCs
      OVX), angiogenic differentiation of human umbilical vein endothelial cells
      (HUVECs) were investigated. The in vitro results showed that Sr and Si ions
      released from SrCS enhanced cell viability, alkaline phosphatase (ALP) activity,
      and mRNA expression levels of osteoblast-related genes of rBMSCs-OVX and
      expression of vascular endothelial growth factor (VEGF) without addition of extra
      osteogenic and angiogenic reagents. The activation in extracellular signal
      related kinases (ERK) and p38 signaling pathways were observed in rBMSCs-OVX
      cultured in the extract of SrCS, and these effects could be blocked by ERK
      inhibitor PD98059, and P38 inhibitor SB203580, respectively. Furthermore, the
      ionic extract of SrCS stimulated HUVECs proliferation, differentiation and
      angiogenesis process. The in vivo experiments revealed that SrCS dramatically
      stimulated bone regeneration and angiogenesis in a critical sized OVX calvarial
      defect model, and the enhanced bone regeneration might be attributed to the
      modulation of osteogenic differentiation of endogenous mesenchymal stem cells
      (MSCs) and the inhibition of osteoclastogenesis, accompanying with the promotion
      of the angiogenic activity of endothelial cells (ECs).

PMID- 24095252
TI  - Automated procedure for biomimetic de-cellularized lung scaffold supporting
      alveolar epithelial transdifferentiation.
AB  - The optimal method for creating a de-cellularized lung scaffold that is devoid of
      cells and cell debris, immunologically inert, and retains necessary extracellular
      matrix (ECM) has yet to be identified. Herein, we compare automated detergent
      based de-cellularization approaches utilizing either constant pressure (CP) or
      constant flow (CF), to previously published protocols utilizing manual pressure
      (MP) to instill and rinse out the de-cellularization agents. De-cellularized
      lungs resulting from each method were evaluated for presence of remaining ECM
      proteins and immunostimulatory material such as nucleic acids and intracellular
      material. Our results demonstrate that the CP and MP approaches more effectively
      remove cellular materials but differentially retain ECM proteins. The CP method
      has the added benefit of being a faster, reproducible de-cellularization process.
      To assess the functional ability of the de-cellularized scaffolds to maintain
      epithelial cells, intra-tracheal inoculation with GFP expressing C10 alveolar
      epithelial cells (AEC) was performed. Notably, the CP de-cellularized lungs were
      able to support growth and spontaneous differentiation of C10-GFP cells from a
      type II-like phenotype to a type I-like phenotype.

PMID- 24095253
TI  - Polymer-based mesh as supports for multi-layered 3D cell culture and assays.
AB  - Three-dimensional (3D) culture systems can mimic certain aspects of the cellular
      microenvironment found in vivo, but generation, analysis and imaging of current
      model systems for 3D cellular constructs and tissues remain challenging. This
      work demonstrates a 3D culture system-Cells-in-Gels-in-Mesh (CiGiM)-that uses
      stacked sheets of polymer-based mesh to support cells embedded in gels to form
      tissue-like constructs; the stacked sheets can be disassembled by peeling the
      sheets apart to analyze cultured cells-layer-by-layer-within the construct. The
      mesh sheets leave openings large enough for light to pass through with minimal
      scattering, and thus allowing multiple options for analysis-(i) using
      straightforward analysis by optical light microscopy, (ii) by high-resolution
      analysis with fluorescence microscopy, or (iii) with a fluorescence gel scanner.
      The sheets can be patterned into separate zones with paraffin film-based decals,
      in order to conduct multiple experiments in parallel; the paraffin-based decal
      films also block lateral diffusion of oxygen effectively. CiGiM simplifies the
      generation and analysis of 3D culture without compromising throughput, and
      quality of the data collected: it is especially useful in experiments that
      require control of oxygen levels, and isolation of adjacent wells in a multi-zone
      format.

PMID- 24095254
TI  - The effect of the coumarin-like derivative osthole on the osteogenic properties
      of human periodontal ligament and jaw bone marrow mesenchymal stem cell sheets.
AB  - Cell sheet engineering is a scaffold-free delivery concept that has been shown to
      improve mesenchymal stem cell-mediated regeneration of injured or pathologically
      damaged periodontal tissues in preclinical studies and several clinical trials.
      However, the best strategy for cell sheet production remains to be identified.
      The aim of this study was to investigate the biological effects of osthole, a
      coumarin-like derivative extracted from Chinese herbs, on the cell sheet
      formation and osteogenic properties of human periodontal ligament stem cells
      (PDLSCs) and jaw bone marrow mesenchymal stem cells (JBMMSCs). Patient-matched
      PDLSCs and JBMMSCs were isolated, and an appropriate concentration of osthole for
      cell culture was screened for both cell types in terms of cell proliferation and
      alkaline phosphatase (ALP) activity. Next, the best mode of osthole stimulation
      for inducing the formation of sheets by each cell type was selected by evaluating
      the amount of their extracellular matrix (ECM) protein production as well as
      osteogenic-related gene expression. Furthermore, both PDLSC and JBMMSC sheets
      obtained from each optimized technique were transplanted subcutaneously into nude
      mice to evaluate their capacity for ectopic bone regeneration. The results
      revealed that 10(-5) m/L osthole significantly enhanced the proliferation of both
      PDLSCs and JBMMSCs (P < 0.05), although for JBMMSCs, there was no concentration
      related change among the four established osthole groups (P > 0.05). In addition,
      10(-5) m/L osthole was the best concentration to promote the ALP activities of
      both cells (P < 0.01). Based on both the production of ECM proteins (collagen
      type I, integrin beta1, and fibronectin) and the expression of osteogenic genes
      (ALP, Runt-related transcription factor 2 (RUNX2), and osteocalcin (OCN)), the
      provision of 10(-5) m/L osthole throughout the entire culture stage (10 days) for
      PDLSCs or at the early stage (first 3 days) for JBMMSCs was the most effective
      osthole administration mode for cell sheet formation (P < 0.05). The results of
      in vivo transplantation showed that osthole-mediated PDLSC and JBMMSC sheets
      formed more new bone than those obtained without osthole intervention (P <
      0.001). Our data suggest that a suitable concentration and mode of osthole
      stimulation may enhance ECM production and positively affect cell behavior in
      cell sheet engineering.

PMID- 24095255
TI  - The effect of synthetic oxygen carrier-enriched fibrin hydrogel on Schwann cells
      under hypoxia condition in vitro.
AB  - Schwann cell (SC), which plays a key role in peripheral nerve regeneration, is
      one of the most classic supportive cells in neural tissue engineering. However,
      the biological activity of SCs seeded in nerve scaffolds decays subsequently due
      to local hypoxia induced by ischemia. Thus, we aimed to investigate whether a
      synthetic oxygen carrier-enriched fibrin gel would provide a sustained oxygen
      release to cultured SCs in vitro for overcoming a temporary (48 h) oxygen
      deprivation. In this study, perfluorotributylamine (PFTBA)-based oxygen carrying
      fibrin gel was prepared to provide oxygen for SCs under normoxic or hypoxic
      conditions. The dissolved oxygen within the culture media was measured by a blood
      gas analyzer to quantify the time course of oxygen release from the PFTBA
      enriched fibrin gel. SCs were cultured in the presence or absence of PFTBA
      enriched fibrin gel under normoxic or hypoxic conditions. The tolerance of SCs to
      hypoxia was examined by a cell apoptosis assay. The growth of cells was
      characterized using S-100 staining and a CCK-8 assay. The migration of cells was
      examined using a Transwell chamber. The mRNA of brain-derived neurotrophic factor
      (BDNF), nerve growth factor (NGF), glial cell derived neurotrophic factor (GDNF),
      neural cell adhesion molecule (N-CAM) and vascular endothelial growth factor
      (VEGF) in SCs were assayed by RT-PCR. In addition, SCs cultured in 3D PFTBA
      enriched hydrogel were characterized by Live/Dead staining and the mRNA levels of
      BDNF, NGF, GDNF, N-CAM and VEGF were assayed by RT-PCR. The results showed that
      the PFTBA-enriched fibrin hydrogel was able to promote cell adhesion, migration,
      and proliferation under hypoxic conditions. Interestingly, PFTBA applied through
      the fibrin hydrogel dramatically enhanced the mRNA of BDNF, NGF, GDNF, N-CAM and
      VEGF under hypoxic condition. These findings highlight the possibility of
      enhancing nerve regeneration in cellular nerve grafts through PFTBA increased
      neurotropic secretion in SCs.

PMID- 24095256
TI  - Bacteria with ACC deaminase can promote plant growth and help to feed the world.
AB  - To feed all of the world's people, it is necessary to sustainably increase
      agricultural productivity. One way to do this is through the increased use of
      plant growth-promoting bacteria; recently, scientists have developed a more
      profound understanding of the mechanisms employed by these bacteria to facilitate
      plant growth. Here, it is argued that the ability of plant growth-promoting
      bacteria that produce 1-aminocyclopropane-1-carboxylate (ACC) deaminase to lower
      plant ethylene levels, often a result of various stresses, is a key component in
      the efficacious functioning of these bacteria. The optimal functioning of these
      bacteria includes the synergistic interaction between ACC deaminase and both
      plant and bacterial auxin, indole-3-acetic acid (IAA). These bacteria not only
      directly promote plant growth, they also protect plants against flooding,
      drought, salt, flower wilting, metals, organic contaminants, and both bacterial
      and fungal pathogens. While a considerable amount of both basic and applied work
      remains to be done before ACC deaminase-producing plant growth-promoting bacteria
      become a mainstay of plant agriculture, the evidence indicates that with the
      expected shift from chemicals to soil bacteria, the world is on the verge of a
      major paradigm shift in plant agriculture. 

PMID- 24095257
TI  - Transcranial direct current stimulation enhances cognitive control during emotion
      regulation.
AB  - BACKGROUND: The ability to cognitively control emotions is critical for mental
      health. Previous studies have identified the dorsolateral prefrontal cortex
      (dlPFC) as a core region in cognitive reappraisal. However, there is only scarce
      evidence whether directly modulating dlPFC activity results in improved
      capacities for cognitive reappraisal. OBJECTIVE: In this study, we used anodal
      transcranial direct current stimulation (tDCS) over the right dlPFC to
      investigate the effects of increased dlPFC excitability on cognitive reappraisal
      as indexed by subjective emotional arousal ratings and skin conductance
      responses. METHODS: The study was designed as a double-blind, between-subjects,
      sham-controlled trial. Half of the healthy participants were randomly assigned to
      receive either active tDCS (n = 21, 1.5 mA for 20 min over the right dlPFC) or
      sham stimulation (n = 21). Participants viewed negative and neutral pictures from
      the International Affective Picture System while they were instructed to either
      downregulate, upregulate or maintain their emotions. After each picture
      presentation, participants rated the intensity of emotional arousal. Skin
      conductance responses and gaze fixation were assessed. RESULTS: Our results
      revealed that anodal prefrontal tDCS during downregulation resulted in decreased
      skin conductance responses and decreased emotional arousal ratings. The opposite
      pattern was observed for the upregulation condition in which anodal tDCS resulted
      in higher arousal ratings accompanied by marginally enhanced skin conductance
      responses. CONCLUSION: Our data indicates that tDCS facilitates cognitive
      reappraisal in both directions by either increasing or decreasing emotional
      responsiveness depending on the regulatory goal. This provides further evidence
      for the potential use of tDCS as a tool to modulate cognitive reappraisal.
      However, given the limitations of the present study, our findings need to be
      replicated and complimented by further studies.

PMID- 24095258
TI  - Polymorphisms of the NOS3 gene and risk of myocardial infarction in the Tunisian
      population.
AB  - Controversial results regarding the association of eNOS gene (NOS3) polymorphisms
      with myocardial infarction (MI) have been reported. This study investigated the
      relationship of the -786T>C (rs2070744), 894G>T (rs1799983) and 4a4b
      polymorphisms of the NOS3 gene with the presence of MI in the Tunisian
      population. In addition, we also examined the association of NOS3 gene haplotypes
      with MI in Tunisian subjects. A total of 303 patients with MI and 225 controls
      were included in the study. The 894G>T and -786T>C single nucleotide
      polymorphisms were analyzed by PCR-RFLP, and 4a4b polymorphism just for PCR.
      There was significant linkage disequilibrium between the three NOS3 polymorphisms
      (p<0.0001). The genotype distribution and allele frequency of NOS3 4a4b, but not 
      786T>C and 894G>T, polymorphism was significantly different between MI patients
      and controls. The univariate logistic regression analysis showed a significant
      association of the 4a4b polymorphism and MI according to co-dominant, dominant
      and recessive models (co-dominant model OR: 4.38, 95%CI: 1.24-15.41; p=0.021,
      dominant model OR: 1.66, 95%CI: 1.14-2.42); p=0.007, and recessive model OR:
      3.85, 95%CI: 1.10-13.47; p=0.035). The multivariate analysis, adjusted for
      traditional cardiovascular risk factors, revealed that the NOS3 4a4a genotype was
      an independent predisposing factor to MI, according to the models considered. In
      addition, a haplotype 7 (C-T-4a), (OR=12.05, p=0.010) was a risk factor of MI
      after controlling for classical risk factors. These finding suggest that the 4a4b
      polymorphism of the NOS3 gene was associated with MI in Tunisian patients. 

PMID- 24095259
TI  - Efficacy of tendon stem cells in fibroblast-derived matrix for tendon tissue
      engineering.
AB  - BACKGROUND AIMS: After injury, tendons often heal with poor tissue quality and
      inferior mechanical properties. Tissue engineering using tendon stem cells (TSCs)
      is a promising approach in the repair of injured tendon. Tenogenic
      differentiation of TSCs needs an appropriate environment. More recently, the
      acellular extracellular matrix (ECM) generated from fibroblasts has been used to
      construct various engineering tissues. In this study, we successfully developed
      an engineered tendon tissue formed by seeding TSCs in de-cellularized fibroblast
      derived matrix (dFM). METHODS: Patellar TSCs and dermal fibroblast were isolated
      and cultured. Using the method of osmotic shock, dFM was obtained from dermal
      fibroblast. ECM proteins in dFM were examined. TSCs at passage 3 were seeded in
      dFM for 1 week. Proliferative capacity and characterization of TSCs cultured in
      dFM were determined by population doubling time, immunofluorescence staining and
      quantitative reverse transcriptase polymerase chain reaction. Engineered tendon
      tissue was prepared with dFM and TSCs. Its potentials for neo-tendon formation
      and promoting tendon healing were investigated. RESULTS: dFM is suitable for
      growth and tenogenic differentiation of TSCs in vitro. Neo-tendon tissue was
      formed with tendon-specific protein expression when TSCs were implanted together
      with dFM. In a patellar tendon injury model, implantation of engineered tendon
      tissue significantly improved the histologic and mechanical properties of injured
      tendon. CONCLUSIONS: The findings obtained from our study provide a basis for
      potential use of engineered tendon tissue containing dFM and TSCs in tendon
      repair and regeneration.

PMID- 24095260
TI  - Factors predictive of the perceived osteoporosis-fracture link in fragility
      fracture patients.

PMID- 24095261
TI  - Gulf War illnesses are autoimmune illnesses caused by increased activity of the
      p38/MAPK pathway in CD4+ immune system cells, which was caused by nerve agent
      prophylaxis and adrenergic load.
AB  - Sodium chloride intake might increase the risk for the development of autoimmune
      diseases by increasing the activity of the p38/MAPK pathway in CD4+ cells thereby
      producing pathogenic TH17 cells which are inflammatory. Two factors (muscarinic
      and beta adrenergic stimulation), already shown to potentiate each other's toxic
      effects in whole mice, and have combined amplified sub lethal effects on mouse T
      cells, can have the same effect on CD4+ signaling pathways as sodium chloride.
      Sick 1991 Gulf War veterans express elevated Th17 cytokine activity, and
      therefore may have autoimmune illnesses caused directly by the above mentioned
      exposures. 

PMID- 24095262
TI  - Methylphenidate and the juvenile brain: enhancement of attention at the expense
      of cortical plasticity?
AB  - Methylphenidate (Ritalin) is the most commonly prescribed psychoactive drug for
      juveniles and adolescents. Used to treat attention-deficit/hyperactivity disorder
      (ADHD) and for cognitive enhancement in healthy individuals, it has been regarded
      as a relatively safe medication for the past several decades. However, a thorough
      review of the literature reveals that the age-dependent activities of the drug,
      as well as potential developmental effects, are largely ignored. In addition, the
      diagnosis of ADHD is subjective, leaving open the possibility of misdiagnosis and
      excessive prescription of the drug. Recent studies have suggested that early life
      exposure of healthy rodent models to methylphenidate resulted in altered
      sleep/wake cycle, heightened stress reactivity, and, in fact, a dosage previously
      thought of as therapeutic depressed neuronal function in juvenile rats.
      Furthermore, juvenile rats exposed to low-dose methylphenidate displayed
      alterations in neural markers of plasticity, indicating that the drug might alter
      the basic properties of prefrontal cortical circuits. In this review of the
      current literature, we propose that juvenile exposure to methylphenidate may
      cause abnormal prefrontal function and impaired plasticity in the healthy brain,
      strengthening the case for developing a more thorough understanding of
      methylphenidate's actions on the developing, juvenile brain, as well as better
      diagnostic measures for ADHD. 

PMID- 24095263
TI  - Improvement of intensive care unit sound environment and analyses of consequences
      on sleep: an experimental study.
AB  - OBJECTIVE: Uninterrupted sleep is of vital importance for restoration and
      regaining health. In intensive care units (ICUs) where recovering and healing is
      crucial, patients' sleep often is fragmented and disturbed due to noise from
      activities from oneself, other patients, and alarms. The aim of our study was to
      explore if sleep could be improved by modifying the sound environment in a way
      that is practically feasible in ICUs. METHODS: We studied the effects of
      originally recorded ICU noise and peak reduced ICU noise on sleep in healthy male
      participants. Sleep was registered with polysomnography (PSG) during four nights:
      one adaptation night, one reference (REF) night, and the two exposed nights with
      similar equivalent sound levels (47dB LAeq) but different maximum sound levels
      (56- vs 64-dB LAFmax). The participants answered questionnaires and saliva
      cortisol was sampled in the morning. RESULTS: During ICU exposure nights, sleep
      was more fragmented with less slow-wave sleep (SWS), more arousals, and more time
      awake. The effects of reduced maximum sound level were minor. The subjective data
      supported the polysomnographic findings, though cortisol levels were not
      significantly affected by the exposure conditions. CONCLUSIONS: Noise in ICUs
      impairs sleep and the reduction of maximal A-weighted levels from 64 to 56dB is
      not enough to have a clear improved effect on sleep quality.

PMID- 24095264
TI  - Electroencephalogram slowing in rapid eye movement sleep behavior disorder is
      associated with mild cognitive impairment.
AB  - BACKGROUND: Idiopathic rapid eye movement (REM) sleep behavior disorder (iRBD) is
      a well-documented risk factor for synucleinopathies such as Parkinson disease
      (PD) and dementia with Lewy bodies (DLB). Moreover, approximately 50% of iRBD
      patients have mild cognitive impairment (MCI). The purpose of our study was to
      investigate waking electroencephalogram (EEG) abnormalities specific to iRBD
      patients with MCI. METHODS: Forty-two polysomnographically confirmed iRBD
      patients, including 23 iRBD [+]MCI patients 19 patients without MCI (iRBD [
      ]MCI), and 37 healthy subjects participated in the study. All participants
      underwent a complete neuropsychologic assessment for MCI diagnosis and a waking
      quantitative EEG recording. RESULTS: iRBD [+]MCI patients had a higher slow-to
      fast frequency ratio than iRBD [-]MCI patients and controls in the parietal,
      temporal, and occipital regions. iRBD [+]MCI patients also had higher relative
      theta power in the parietal, temporal, and occipital regions and lower relative
      alpha power in the occipital region compared to iRBD [-]MCI patients and
      controls. Moreover, iRBD [+]MCI patients had higher relative theta power in the
      frontal and central areas and lower relative beta power in the central, parietal,
      and temporal regions compared to controls. The dominant occipital frequency also
      was slower in iRBD [+]MCI patients compared to controls. No between-group
      differences were observed between iRBD [-]MCI patients and controls. CONCLUSION:
      In iRBD patients, only those with concomitant MCI showed waking EEG slowing in
      the posterior cortical regions, providing a potential marker for an increased
      risk for developing DLB or PD.

PMID- 24095265
TI  - Development of a new approach to quantifying stepping stability using ensemble
      empirical mode decomposition.
AB  - Everyday walking is often interrupted by obstacles and changes in the environment
      that make gait a highly non-stationary process. This study introduces a novel
      measure, termed the step stability index (SSI), to quantify stepping stability
      under non-stationary walking conditions among older adults. This index is based
      on the ensemble empirical mode decomposition method. We hypothesized that a
      higher SSI would indicate a more stable gait pattern and could be used to assess
      fall risk. Accelerometer-derived signals (vertical direction) were analyzed from
      39 older adults with a history of 2 or more falls in the past year (i.e.,
      fallers) and 42 older adults who reported no falls in the previous year (i.e.,
      controls) under three walking conditions: baseline walk with and without a
      harness, and obstacle course with a harness. In each condition, the subjects wore
      a small, light-weight sensor (i.e., a 3 dimensional accelerometer) on their lower
      back. The SSI was significantly higher (p <= 0.05) in the controls than in the
      fallers in all three walking conditions. The SSI was significantly (p<0.0001)
      lower for both the controls and the fallers during obstacle walking compared with
      baseline walking. This finding is consistent with a less stable step pattern
      during obstacle negotiation walking. The SSI was correlated with conventional
      clinical measures of mobility and fall risk (the correlation coefficient, r,
      ranged from 0.27 to 0.73, p<0.05). These initial findings suggest that the SSI,
      an index based on the ensemble empirical mode decomposition, may be helpful for
      quantifying gait stability and fall risk during the challenges of everyday
      walking.

PMID- 24095266
TI  - The accuracy of an external frame using ISB recommended rotation sequence to
      define shoulder joint angle.
AB  - When investigating shoulder kinematics, it may be necessary to limit shoulder
      joint angles at a specific level. Previous studies used external frames or
      external surfaces to assist the participant to reach the shoulder joint angles of
      interest. The accuracy of these methods, however, has not yet been investigated.
      In the current study, an external frame was designed to assist in maintaining
      specific shoulder postures in a wide range. The three degrees of freedom of
      rotation of the proposed frame were designed to be consistent with the
      description of shoulder joint angles recommended by the International Society of
      Biomechanics. Six participants used this frame to perform 118 different shoulder
      postures. The reference joint angles measured by a motion tracking system were
      compared with the frame-defined angles. The angle differences among all the
      participants ranged from 12.7 degrees  to 85.6 degrees , with an average of 32.2
      degrees  (SD 15.1 degrees ) across all postures. For the postures with elevation
      angles on or below horizontal, the average angle difference was 23.7 degrees  (SD
      8.5 degrees ). Findings suggest that errors exist when using an external frame to
      assist in reaching specific shoulder postures. Error is minimized at elevation
      angles close to -30 degrees , and the performance is poor for extreme shoulder
      postures.

PMID- 24095268
TI  - Can we do better preventing thromboembolic events following pelvic and acetabular
      injuries?

PMID- 24095267
TI  - Referent body weight values in over ground walking, over ground jogging,
      treadmill jogging, and elliptical exercise.
AB  - OBJECTIVES: I. To evaluate average percentage body weight (APBW) values and
      weight-bearing distribution percentages (WBDP) between four common sports
      activities in a referent adult population. II. To suggest clinical implications.
      DESIGN: Original research study. SETTING: Lerner Sports Center, Hebrew
      University, Mount Scopus, Jerusalem, Israel. PARTICIPANTS: Seventy-five
      asymptomatic volunteers, mean age=33.5 (19-72) years SD=15.1, mean weight
      (kg)=70.7 (43-113) SD=14.1. INTERVENTIONS: Four tests were conducted: 1.
      Overground walking (OGW) over a 20 m distance, 2. Overground jogging (OGJ) over a
      20 m distance, 3. Treadmill jogging (TJ) at a constant speed of 8.5 km/h for a 15
      second interval and 4. Elliptical exercise (EE) for a 20 second period at a
      resistance and incline level of 10, and a steady pace within the range of 70-95
      steps/min. MAIN OUTCOME MEASURE: The SmartstepTM weight-bearing gait analysis
      system. RESULTS: The APBW value on the entire foot in OGW was 112% (SD=15.57), in
      OGJ, 201% (SD=31.24, in TJ, 175% (SD=25.48) and in EE, 73% (SD=13.8). Regarding
      WBDP, the swing phase in OGJ and TJ was significantly longer than the stance
      phase (p<0.05). OGW resulted in significantly less swing phase compared to OGJ
      and TJ (p<0.05). CONCLUSIONS: EE significantly reduces weight-bearing as compared
      to other common functional and sporting activities. These findings may assist the
      rehabilitation team when considering returning individuals back to early activity
      following certain bony or soft tissue pathologies or lower-limb surgical
      procedures. This information is also useful from a repetitive loading standpoint
      (to prevent overuse injury) or for exercise recommendations for those at greater
      risk for exacerbating chronic joint pathology.

PMID- 24095269
TI  - The clinical features of periorbital ecchymosis in a series of trauma patients.
AB  - INTRODUCTION: Periorbital ecchymosis (PE) is caused by blood tracking along
      tissue plains into periorbital tissues, causing discoloration in the upper and
      lower eyelids. This clinical feature is most commonly associated with basal skull
      fractures. Our objective is to present the first patient series describing the
      clinical features associated with traumatically induced PE. METHODS: The authors
      retrospectively reviewed 36 consecutive cases of patients presenting to the
      emergency department with PE over a three-year period at St. Michael's Hospital
      in Toronto. Data were obtained using a standardised data acquisition template.
      RESULTS: All patients presented to the emergency department with PE. The mean age
      in our series was 39 years (range 19-88 years), 31 patients were male. PE was
      associated with a variety of injuries including: 15 basal skull fractures, 9 soft
      tissue injuries without fractures, 8 convexity fractures, and 3 facial fractures.
      The other classic signs of basal skull fracture (Battle's sign, hemotympanum,
      cerebrospinal fluid otorrhea, cerebrospinal fluid rhinorrhea) were observed in 3,
      7, 1, and 3 patients with PE, respectively. The most common clinical feature
      associated with PE was cranial nerve injury, observed in 10 patients. Surgical
      intervention was required in 8 patients. Five patients were discharged to a
      rehabilitation centre. No meningitis, cerebral abscess, encephalitis or deaths
      were observed. CONCLUSION: Periorbital ecchymosis is a useful clinic sign that
      should alert the clinician to assess for skull fractures, intracranial
      haemorrhage, and cranial nerve injury. However, this series shows that PE can be
      associated with a variety of clinical features, is rarely accompanied by other
      classic signs of basal skull fracture, and most patients with PE do not have
      injuries severe enough to require surgical intervention or post-discharge
      rehabilitation.

PMID- 24095270
TI  - Postural control, falls and fear of falling in people with multiple sclerosis
      without mobility aids.
AB  - The purpose of the study was to determine the relationship between static
      postural control parameters to fear of falling and falling history in people with
      multiple sclerosis (MS) without mobility assistive devices. One-hundred and seven
      relapsing-remitting patients diagnosed with MS, 62 women aged 42.8 (S.D.=12.0),
      participated in this investigation. Participants were divided into groups based
      on fall history; 47 had no history during the past 6 months and 60 had a history
      of at least one fall within the same period. Static postural control parameters
      were obtained from the Zebris FDM-T Treadmill (zebris(r) Medical GmbH, Germany).
      The patient's self-reported questionnaire, the Falls Efficacy Scale International
      (FES-I), was used to assess the level of concern relating to falls. People with
      MS classified as fallers exhibited increased center of pressure (CoP) path
      length, sway velocity and greater overall sway area. CoP path length performed
      with eyes open was found to explain 42% of the variance related to at least one
      fall during the past six months; R(2)=0.424, chi(2)(1)=40.727, P<0.01. The
      correlation between the FES-I and CoP path length was 0.620 (P<0.001).
      Measurement of the CoP trajectories with instrumented posturography should be
      considered in managing fall risk in the MS population.

PMID- 24095271
TI  - Effects of accelerated senescence on learning and memory, locomotion and anxiety
      like behavior in APP/PS1 mouse model of Alzheimer's disease.
AB  - Alzheimer's disease (AD) is characterized by a deficit in motor and spatial
      learning-memory and alteration of non-cognitive behavior. The generation of
      transgenic mice with presence of AD pathologies that cause learning and memory
      deficits has led to improved understanding of the behavioral and
      pathophysiological processes underlying AD. A novel APP/PS1 mouse model in the
      senescence accelerated mouse prone 8 (SAMP8) background--SAMP8 APP/PS1 was
      generated. To assess the behavioral and other AD-related changes in this SAMP8
      APP/PS1 model, the present report covers a phenotypical analysis of this model
      for working memory, spatial memory, motor performance and anxiety-like behavior.
      SAMP8 APP/PS1 mice showed motor and spatial memory impairments, together with an
      increase of locomotor activity and lower anxiety-like behavior at 9months old. In
      contrast, C57 APP/PS1 and SAMP8 wild type mice were inconspicuous in all of these
      tasks and properties except C57 APP/PS1 mice which showed motor memory impairment
      in the shuttle box task at 9 months old. Standard senescence-associated beta
      galactosidase (SA-beta-GAL) staining and amyloid beta (Abeta)
      immunohistochemistry showed more severe pathological changes in the SAMP8 APP/PS1
      mice. SAMP8 APP/PS1 mice exhibited earlier deficits in their non-cognitive and
      cognitive behaviors which are coincident in the AD patient and the results
      suggest that this new type of mice might be a better model for studying the age
      related dementia of the Alzheimer type and for assessing the potential
      therapeutic agents for AD.

PMID- 24095272
TI  - Impact of non-motor symptoms on the quality of life of patients with Parkinson's
      disease: some questions beyond research findings.

PMID- 24095273
TI  - Cardiovascular mortality in Hispanics compared to non-Hispanic whites: a
      systematic review and meta-analysis of the Hispanic paradox.
AB  - BACKGROUND: Hispanics, the largest minority in the U.S., have a higher prevalence
      of several cardiovascular (CV) risk factors than non-Hispanic whites (NHW).
      However, some studies have shown a paradoxical lower rate of CV events among
      Hispanics than NHW. OBJECTIVE: To perform a systematic review and a meta-analysis
      of cohort studies comparing CV mortality and all-cause mortality between Hispanic
      and NHW populations in the U.S. METHODS: We searched EMBASE, MEDLINE, Web of
      Science, and Scopus databases from 1950 through May 2013, using terms related to
      Hispanic ethnicity, CV diseases and cohort studies. We pooled risk estimates
      using the least and most adjusted models of each publication. RESULTS: We found
      341 publications of which 17 fulfilled the inclusion criteria; data represent
      22,340,554 Hispanics and 88,824,618 NHW, collected from 1950 to 2009. Twelve of
      the studies stratified the analysis by gender, and one study stratified people by
      place of birth (e.g. U.S.-born, Mexican-born, and Central/South American-born).
      There was a statistically significant association between Hispanic ethnicity and
      lower CV mortality (OR 0.67; 95% CI, 0.57-0.78; p<0.001), and lower all-cause
      mortality (0.72; 95% CI, 0.63-0.82; p<0.001). A subanalysis including only
      studies that reported prevalence of CV risk factors found similar results. OR for
      CV mortality among Hispanics was 0.49; 95% CI 0.30-0.80; p-value <0.01; and OR
      for all-cause mortality was 0.66; 95% CI 0.43-1.02; p-value 0.06. CONCLUSION:
      These results confirm the existence of a Hispanic paradox regarding CV mortality.
      Further studies are needed to identify the mechanisms mediating this protective
      CV effect in Hispanics.

PMID- 24095274
TI  - Five types of OECD healthcare systems: empirical results of a deductive
      classification.
AB  - This article classifies 30 OECD healthcare systems according to a deductively
      generated typology by Rothgang and Wendt [1]. This typology distinguishes three
      core dimensions of the healthcare system: regulation, financing, and service
      provision, and three types of actors: state, societal, and private actors. We
      argue that there is a hierarchical relationship between the three dimensions, led
      by regulation, followed by financing and finally service provision, where the
      superior dimension restricts the nature of the subordinate dimensions. This
      hierarchy rule limits the number of theoretically plausible types to ten. To test
      our argument, we classify 30 OECD healthcare systems, mainly using OECD Health
      Data and WHO country reports. The classification results in five system types:
      the National Health Service, the National Health Insurance, the Social Health
      Insurance, the Etatist Social Health Insurance, and the Private Health System.
      All five types belong to the group of healthcare system types considered
      theoretically plausible. Merely Slovenia does not comply with our assumption of a
      hierarchy among dimensions and typical actors due to its singular transformation
      history. 

PMID- 24095275
TI  - A theoretical framework for holistic hospital management in the Japanese
      healthcare context.
AB  - OBJECTIVE: This paper develops a conceptual framework for performance measurement
      as a pilot study on holistic hospital management in the Japanese healthcare
      context. METHODS: We primarily used two data sources as well as expert statements
      obtained through interviews: a systematic review of literature and a
      questionnaire survey to healthcare experts. The systematic survey searched PubMed
      and PubMed Central, and 24 relevant papers were elicited. The expert
      questionnaire asked respondents to rate the degree of "usefulness" for each of 66
      indicators on a three-point scale. RESULTS: Applying the theoretical framework, a
      minimum set of performance indicators was selected for holistic hospital
      management, which well fit the healthcare context in Japan. This indicator set
      comprised 35 individual indicators and several factors measured through
      questionnaire surveys. The indicators were confirmed by expert judgments from
      viewpoints of face, content and construct validities as well as their usefulness.
      CONCLUSION: A theoretical framework of performance measurement was established
      from primary healthcare stakeholders' perspectives. Performance indicators were
      largely divided into healthcare outcomes and performance shaping factors.
      Indicators in the former category may be applied for the detection of operational
      problems, while their latent causes can be effectively addressed by the latter
      category in terms of process, structure and culture/climate within the
      organization.

PMID- 24095276
TI  - Syntaxin 13, a genetic modifier of mutant CHMP2B in frontotemporal dementia, is
      required for autophagosome maturation.
AB  - Phagophore maturation is a key step in the macroautophagy pathway, which is
      critical in many important physiological and pathological processes. Here we
      identified Drosophila N-ethylmaleimide-sensitive fusion protein 2 (dNSF2) and
      soluble NSF attachment protein (Snap) as strong genetic modifiers of mutant
      CHMP2B, an ESCRT-III component that causes frontotemporal dementia and
      autophagosome accumulation. Among several SNAP receptor (SNARE) genes, Drosophila
      syntaxin 13 (syx13) exhibited a strong genetic interaction with mutant CHMP2B.
      Knockdown of syntaxin 13 (STX13) or its binding partner Vti1a in mammalian cells
      caused LC3-positive puncta to accumulate and blocks autophagic flux. STX13 was
      present on LC3-positive phagophores induced by rapamycin and was highly enriched
      on multilamellar structures induced by dysfunctional ESCRT-III. Loss of STX13
      also caused the accumulation of Atg5-positive puncta and the formation of
      multilamellar structures. These results suggest that STX13 is a genetic modifier
      of ESCRT-III dysfunction and participates in the maturation of phagophores into
      closed autophagosomes. 

PMID- 24095277
TI  - Argonaute and Triman generate dicer-independent priRNAs and mature siRNAs to
      initiate heterochromatin formation.
AB  - RNAi is a conserved mechanism in which small RNAs induce silencing of
      complementary targets. We have previously identified priRNAs, a class of Dicer
      independent small RNAs in fission yeast. The mechanism by which Dicer-independent
      small RNAs are generated is not well understood in any species. Here we
      reconstitute the final steps of priRNA and siRNA biogenesis in vitro. We identify
      the 3'-5' exonuclease Triman and demonstrate that Argonaute, loaded with longer
      RNA precursors, recruits Triman to generate mature priRNAs and siRNAs. We show
      that priRNA and siRNA trimming is required for de novo assembly of
      heterochromatin at centromeric repeats and the mat locus and for maintenance of
      heterochromatin at developmental genes. Furthermore, in rrp6Delta cells RNAi
      targets diverse genes in a Triman-dependent way, indicating that the exosome
      protects the genome from spurious RNAi. Our results suggest that Argonaute
      association with RNA degradation products generates priRNAs and triggers RNAi in
      a process of transcriptome surveillance. 

PMID- 24095278
TI  - Unusual noncanonical intron editing is important for tRNA splicing in Trypanosoma
      brucei.
AB  - In cells, tRNAs are synthesized as precursor molecules bearing extra sequences at
      their 5' and 3' ends. Some tRNAs also contain introns, which, in archaea and
      eukaryotes, are cleaved by an evolutionarily conserved endonuclease complex that
      generates fully functional mature tRNAs. In addition, tRNAs undergo numerous
      posttranscriptional nucleotide chemical modifications. In Trypanosoma brucei, the
      single intron-containing tRNA (tRNA(Tyr)GUA) is responsible for decoding all
      tyrosine codons; therefore, intron removal is essential for viability. Using
      molecular and biochemical approaches, we show the presence of several
      noncanonical editing events, within the intron of pre-tRNA(Tyr)GUA, involving
      guanosine-to-adenosine transitions (G to A) and an adenosine-to-uridine
      transversion (A to U). The RNA editing described here is required for proper
      processing of the intron, establishing the functional significance of
      noncanonical editing with implications for tRNA processing in the deeply
      divergent kinetoplastid lineage and eukaryotes in general. 

PMID- 24095279
TI  - The folliculin tumor suppressor is a GAP for the RagC/D GTPases that signal amino
      acid levels to mTORC1.
AB  - The mTORC1 kinase is a master growth regulator that senses numerous environmental
      cues, including amino acids. The Rag GTPases interact with mTORC1 and signal
      amino acid sufficiency by promoting the translocation of mTORC1 to the lysosomal
      surface, its site of activation. The Rags are unusual GTPases in that they
      function as obligate heterodimers, which consist of RagA or B bound to RagC or D.
      While the loading of RagA/B with GTP initiates amino acid signaling to mTORC1,
      the role of RagC/D is unknown. Here, we show that RagC/D is a key regulator of
      the interaction of mTORC1 with the Rag heterodimer and that, unexpectedly, RagC/D
      must be GDP bound for the interaction to occur. We identify FLCN and its binding
      partners, FNIP1/2, as Rag-interacting proteins with GAP activity for RagC/D, but
      not RagA/B. Thus, we reveal a role for RagC/D in mTORC1 activation and a
      molecular function for the FLCN tumor suppressor. 

PMID- 24095280
TI  - Phosphorylation of BRAF by AMPK impairs BRAF-KSR1 association and cell
      proliferation.
AB  - BRAF is an oncogenic protein kinase that drives cell growth and proliferation
      through the MEK-ERK signaling pathway. BRAF inhibitors have demonstrated
      antitumor efficacy in melanoma therapy but have also been found to be associated
      with the development of cutaneous squamous cell carcinomas (cSCCs) in certain
      patients. Here, we report that BRAF is phosphorylated at Ser729 by AMP-activated
      protein kinase (AMPK), a critical energy sensor. This phosphorylation promotes
      the association of BRAF with 14-3-3 proteins and disrupts its interaction with
      the KSR1 scaffolding protein, leading to attenuation of the MEK-ERK signaling. We
      also show that phosphorylation of BRAF by AMPK impairs keratinocyte cell
      proliferation and cell-cycle progression. Furthermore, AMPK activation attenuates
      BRAF inhibitor-induced ERK hyperactivation in keratinocytes and epidermal
      hyperplasia in mouse skin. Our findings reveal a mechanism for regulating BRAF
      signaling in response to energy stress and suggest a strategy for preventing the
      development of cSCCs associated with BRAF-targeted therapy. 

PMID- 24095281
TI  - Metabolic activation of CaMKII by coenzyme A.
AB  - Active metabolism regulates oocyte cell death via calcium/calmodulin-dependent
      protein kinase II (CaMKII)-mediated phosphorylation of caspase-2, but the link
      between metabolic activity and CaMKII is poorly understood. Here we identify
      coenzyme A (CoA) as the key metabolic signal that inhibits Xenopus laevis oocyte
      apoptosis by directly activating CaMKII. We found that CoA directly binds to the
      CaMKII regulatory domain in the absence of Ca(2+) to activate CaMKII in a
      calmodulin-dependent manner. Furthermore, we show that CoA inhibits apoptosis not
      only in X. laevis oocytes but also in Murine oocytes. These findings uncover a
      direct mechanism of CaMKII regulation by metabolism and further highlight the
      importance of metabolism in preserving oocyte viability.

PMID- 24095282
TI  - Molecular mechanism of bacterial persistence by HipA.
AB  - HipA of Escherichia coli is a eukaryote-like serine-threonine kinase that
      inhibits cell growth and induces persistence (multidrug tolerance). Previously,
      it was proposed that HipA inhibits cell growth by the phosphorylation of the
      essential translation factor EF-Tu. Here, we provide evidence that EF-Tu is not a
      target of HipA. Instead, a genetic screen reveals that the overexpression of
      glutamyl-tRNA synthetase (GltX) suppresses the toxicity of HipA. We show that
      HipA phosphorylates conserved Ser(239) near the active center of GltX and
      inhibits aminoacylation, a unique example of an aminoacyl-tRNA synthetase being
      inhibited by a toxin encoded by a toxin-antitoxin locus. HipA only phosphorylates
      tRNA(Glu)-bound GltX, which is consistent with the earlier finding that the
      regulatory motif containing Ser(239) changes configuration upon tRNA binding.
      These results indicate that HipA mediates persistence by the generation of
      "hungry" codons at the ribosomal A site that trigger the synthesis of (p)ppGpp, a
      hypothesis that we verify experimentally. 

PMID- 24095283
TI  - Belgian general practitioners' perspectives on the use of palliative sedation in
      end-of-life home care: a qualitative study.
AB  - CONTEXT: Palliative sedation (PS) is a far-reaching palliative measure with a
      life-shortening potential. Guidelines provide only for a restricted use of PS and
      as a last resort. OBJECTIVES: To explore PS practice in end-of-life (EoL) home
      care. METHODS: This was a qualitative analysis of semi-structured interviews with
      52 general practitioners (GPs) of Flanders, Belgium. RESULTS: Apart from GPs who
      adhere to the existing prerequisites for PS, opinions diverge among GPs on the
      indication area for PS and on possible life-shortening intentions. The key to
      GPs' broadened view on "which suffering merits PS" is the fragile context of EoL
      home care, and the key to GPs' possible life-shortening intentions is their need
      to facilitate the dying process, when trying or lengthy. When honoring a
      terminally ill patient's request for euthanasia, several GPs prefer slow
      euthanasia using PS to a lethal injection. CONCLUSION: PS home practice deviates
      from the PS guidelines' recommendations. In addition to the GPs' shortage of
      knowledge, the guidelines' recommendations do not always meet the particular
      needs of EoL home care. If one consideration of EoL home care is to respect a
      patient's wish to die at home, then the pre-emptive use of PS to avoid a futile
      transfer to the hospital in the case of an undesirable turn of events deserves
      more attention in the PS debate.

PMID- 24095284
TI  - A new focus on breakthrough cancer pain: commentary on Davies et al.

PMID- 24095285
TI  - Definition, categorization, and terminology of episodic breathlessness: consensus
      by an international Delphi survey.
AB  - CONTEXT: Episodic breathlessness is a common and distressing symptom in patients
      with advanced disease. Still, it is not yet clearly defined. OBJECTIVES: The aim
      of this work was to develop an international definition, categorization, and
      terminology of episodic breathlessness. METHODS: An online Delphi survey was
      conducted with international breathlessness experts. We used a structured
      questionnaire to identify specific aspects and reach agreement on a definition,
      categorization, and terminology (five-point Likert scale). Consensus was defined
      in advance as >=70% agreement. RESULTS: Thirty-one of 68 (45.6%), 29 of 67
      (43.3%), and 33 of 67 (49.3%) experts responded in the first, second, and third
      rounds, respectively. Participants were 20-79 years old, about 60% male, and more
      than 75% rated their own breathlessness expertise as moderate to high. After
      three rounds, consensus was reached on a definition, categorization, and
      terminology (84.4%, 96.3%, and 92.9% agreement). The final definition includes
      general and qualitative aspects of the symptom, for example, time-limited severe
      worsening of intensity or unpleasantness of breathlessness in the patient's
      perception. Categories are predictable or unpredictable, depending on whether any
      triggers can be identified. CONCLUSION: There is high agreement on clinical and
      operational aspects of episodic breathlessness in advanced disease among
      international experts. The consented definition and categorization may serve as a
      catalyst for clinical and basic research to improve symptom control and patients'
      quality of life.

PMID- 24095286
TI  - Current state of psychiatric involvement on palliative care consult services:
      results of a national survey.
AB  - CONTEXT: Palliative care consult services have emerged as an excellent resource
      for physicians seeking help with patients' symptoms. Symptoms include those of a
      psychiatric nature (e.g., depression, anxiety, delirium); however, little
      information is known about whether palliative care services include psychiatric
      input as part of multidisciplinary teams. OBJECTIVES: To explore 1) the current
      level of collaboration between psychiatrists and palliative care consult services
      across the U.S. and 2) the factors that support or restrict such involvement.
      METHODS: A national survey was developed and distributed electronically to
      program directors identified in the National Palliative Care Registry maintained
      by the Center to Advance Palliative Care. Analyses examined trends in psychiatry
      involvement with hospital-based palliative care teams. RESULTS: The survey had a
      59% response rate, with final analyses including surveys completed by 260
      palliative care program directors (67% inclusion rate from total respondents).
      Seventy-two percent of respondents reported some form of involvement with a
      psychiatrist on their palliative care service, with only 10% of those identifying
      a psychiatrist as a full- or part-time member of the team. Most respondents
      reported that they would like psychiatrists to be more involved with the
      palliative care services (71%). Secondary analyses of qualitative responses
      identified common impediments to increased psychiatry involvement, which included
      financial constraints, provider interest, and perceived disciplinary disconnect.
      CONCLUSION: There are shared objectives between psychiatry and palliative care;
      however, currently, co-involvement on treatment teams is quite limited. Future
      research is needed to identify ways to facilitate the interface of palliative
      care and psychiatry.

PMID- 24095287
TI  - [Is MRI monitoring useful in clinical practice in patients with multiple
      sclerosis? Comments].

PMID- 24095288
TI  - Thrombosis in inflammatory bowel disease: are we tailoring prophylaxis to those
      most at risk?
AB  - Inflammatory bowel disease (IBD) is a disease-specific risk factor for incident
      and recurrent venous thromboembolism (VTE). The reasons are acquired,
      multifactorial, and related to prothrombotic aberrations during active disease,
      although the mechanisms remain incompletely elucidated. VTE represents a
      potentially life-threatening extraintestinal manifestation of IBD, but the
      associated morbidity and mortality can be reduced by appropriate use of
      thromboprophylaxis. Nevertheless, despite international guidelines advocating
      thromboprophylaxis in hospitalised patients with IBD, practice is highly
      variable, since 65% of gastroenterologists may not use pharmacological VTE
      prophylaxis in hospitalised patients with acute severe colitis. Furthermore,
      there is no guidance on appropriate prophylaxis for ambulatory outpatients with
      active disease who are at an appreciable risk of VTE. Thus the question: are we
      tailoring thromboprophylaxis to those patients with IBD who are most at risk? 

PMID- 24095289
TI  - Dental pulp stem cells for in vivo bone regeneration: a systematic review of
      literature.
AB  - OBJECTIVE: This review of literature was aimed to assess in vivo experiments
      which have evaluated the efficacy of dental pulp stem cells (DPSCs) for bone
      regeneration. DESIGN: An electronic search of English-language papers was
      conducted on PubMed database. Studies that assessed the use of DPSCs in bone
      regeneration in vivo were included and experiments evaluating regeneration of
      hard tissues other than bone were excluded. The retrieved articles were
      thoroughly reviewed according to the source of stem cell, cell carrier, the in
      vivo experimental model, defect type, method of evaluating bone regeneration, and
      the obtained results. Further assessment of the results was conducted by
      classifying the studies based on the defect type. RESULTS: Seventeen papers
      formed the basis of this systematic review. Sixteen out of 17 experiments were
      performed on animal models with mouse and rat being the most frequently used
      animal models. Seven out of 17 animal studies, contained subcutaneous pockets on
      back of the animal for stem cell implantation. In only one study hard tissue
      formation was not observed. Other types of defects used in the retrieved studies,
      included cranial defects and mandibular bone defects, in all of which bone
      formation was reported. CONCLUSION: When applied in actual bone defects, DPSCs
      were capable of regenerating bone. Nevertheless, a precise conclusion regarding
      the efficiency of DPSCs for bone regeneration is yet to be made, considering the
      limited number of the in vivo experiments and the heterogeneity within their
      methods.

PMID- 24095290
TI  - Evaluation of tumor blood flow after feeder embolization in meningiomas by
      arterial spin-labeling perfusion magnetic resonance imaging.
AB  - Preoperative embolization changes the amount of blood flow and pattern of flow
      distribution in meningioma. Tumor blood flow was investigated in eight meningioma
      patients before and after embolization using arterial spin-labeling (ASL)
      perfusion imaging. Although blood flow was significantly reduced in the whole
      tumor after embolization, changes in flow distribution patterns varied from one
      case to another. The findings suggest that evaluation of post-embolization tumor
      blood flow by ASL perfusion imaging would be useful in the surgical planning of
      meningioma. 

PMID- 24095291
TI  - Computed anatomical modelling of the optic pathway and oculomotor system using
      magnetic resonance imaging.
AB  - This study presents a computer-based tool for three-dimensional (3D)
      visualization of the optic pathway and oculomotor system using 3D high-resolution
      magnetic resonance imaging (MRI) datasets from a healthy subject. The 3D models
      were built as wireframe grids co-registered with MRI sections. First, 3D
      anatomical models were generated of the visual pathway from the eyeball to the
      primary visual cortex and of the cranial oculomotor nerves from the brain stem to
      the extrinsic eye muscles. Second, a graphical user interface allowed individual
      and group visualization, translation, rotation and zooming of the 3D models in
      different spatial positions simultaneously with MRI orthogonal cut planes.
      Educational and clinical applications are also discussed. 

PMID- 24095292
TI  - A case of Terson syndrome and its mechanism of bleeding.

PMID- 24095293
TI  - [Severe punding in Parkinson's disease].
AB  - BACKGROUND: Punding is a stereotypical behavior characterized by an intense
      fascination with repetitive handling and examining of mechanical devices or
      arranging common objects. This condition, which is different from both obsessive
      compulsive disorder and mania, is still underestimated in patients with
      Parkinson's disease and may have deleterious social consequences on patients and
      their families. CASE REPORT: We report the case of severe punding in a 23-year
      old parkinsonian woman, who presented, a few days following a rise in the dose of
      pergolide up to 2,5 mg/(d), frequent and daily unusual repetitive behavior,
      characterized by ceaseless sewing, disassembly and reassembly of phones, and
      coloring of drawings. These behaviors were associated with a common peak of dose
      dyskinesia and were responsible for a considerable reduction in duration of sleep
      with negative impact on the quality of life of her parents. These symptoms
      significantly improved immediately after switching pergolide to an equivalent
      dose of ropinirole (12 mg/(d). DISCUSSION: Punding has only recently come to the
      attention of physicians through the first report in a parkinsonian patient,
      triggered by dopaminergic replacement therapy. The phenomenon was thought to be
      related to excessive dopaminergic stimulation of the limbic and associative
      pathways. The current mainstay of treatment is the reduction in the dose of
      dopaminergic medication or changing the presumed responsible drug, often a
      dopaminergic agonist. In this article, the authors review the epidemiology,
      pathophysiology and management of this curious phenomenon.

PMID- 24095294
TI  - [Experience of liaison psychiatry in Morocco: transversal study over 24 months].
AB  - INTRODUCTION: Liaison psychiatry is a discipline caring for psychiatric disorders
      in patients of general hospitals. It involves clinical, educational, and research
      aspects. The liaison psychiatry supports patients hospitalized for full-time in
      medical and surgical departments, patients admitted in day-hospital and patients
      treated in the emergency department. In this transversal study, we assessed the
      liaison psychiatry impact that is still in development stage in Morocco. This
      study lasted 24 months, and was conducted at the University Hospital in Fez,
      Morocco. OBJECTIVES: The goal of this work was to evaluate the prevalence of
      psychiatric disorders managed by liaison psychiatry, identify those requiring
      medical and surgical departments of such psychiatric support, and classify the
      motivations involved in their needs. METHODS: This transversal study was
      initiated in January 2010 and has lasted 24 months. The study recruited 180
      patients requiring psychiatric consultation from different medical and surgical
      departments at the University Hospital in Fes, Morocco. The psychiatric
      assessment was based on a psychiatric interview using the MINI. The data were
      collected by a certified psychiatrist using a questionnaire containing 24 items.
      After initial psychiatric assessment, the follow-up was proposed to the patient
      in the psychiatric department. RESULTS: During this study, 22 medical and
      surgical departments of our University Hospital had requested a psychiatric
      assessment for their patients. Most demands were respectively emitted by the
      Department of Dermatology (16%) and Nephrology (11%). The most common motivations
      for psychiatric consultations were respectively psychomotor agitation (17%) and
      an evaluation of suicide attempts (17%). Depressive and psychotic disorders were
      the most diagnosed disorders with 47% and 11% respectively. The psychiatric
      support was based on pharmacological treatment in 60% of cases. Finally, the
      outcome was favourable in 80% of followed cases. CONCLUSION: Hospitalized
      patients in different medical and surgical departments of the University Hospital
      of Fez have demonstrated a high prevalence of psychiatric disorders. This
      constitutes a very strong motivation to setup a department of liaison psychiatry.
      This would allow a better psychiatric support and follow-up of patients.

PMID- 24095295
TI  - [Relations between nicotine dependence and cannabis dependence in adolescents].

PMID- 24095297
TI  - Etirinotecan pegol: an option for late-stage breast cancer?

PMID- 24095296
TI  - A critical review of trials of first-line BCR-ABL inhibitor treatment in patients
      with newly diagnosed chronic myeloid leukemia in chronic phase.
AB  - BACKGROUND: The characteristic expression of the constitutively active
      oncoprotein, BCR-ABL tyrosine kinase, in chronic myeloid leukemia (CML) was the
      basis for the development of BCR-ABL tyrosine kinase inhibitors for treatment.
      Three BCR-ABL inhibitors, imatinib, nilotinib, and dasatinib, have been approved
      by the US Food and Drug Administration for first-line treatment of patients with
      newly diagnosed CML in chronic phase (CML-CP). METHODS: This article reviews the
      key phase III clinical trials supporting the use of first-line imatinib,
      nilotinib, and dasatinib in patients with CML-CP, as well as findings of
      supportive phase II studies. RESULTS: At the time of its approval in 2001,
      imatinib induced unprecedented response rates in patients with CML-CP; however,
      resistance and intolerance to imatinib prevent 20% to 30% of patients from
      deriving full therapeutic benefit. Nilotinib and dasatinib, both approved in 2010
      for first-line CML-CP treatment, are more potent than imatinib and less
      susceptible to imatinib resistance mechanisms. Comparative clinical trials of
      each agent with imatinib have shown that they are associated with significantly
      deeper and more rapid responses than standard-dose imatinib, without compromising
      safety. CONCLUSIONS: Given that evidence suggests achievement of an early
      response is predictive of improved long-term outcomes, earlier use of these
      compounds may lead to more rapid, deeper responses corresponding with
      improvements in patient outcome. Although future studies will benefit from more
      uniform definitions of end points and methods of analysis, data from published
      studies of first-line BCR-ABL inhibitor treatment for patients with newly
      diagnosed CML-CP support the use of dasatinib or nilotinib in place of imatinib.

PMID- 24095298
TI  - Dual HER2 targeting for early breast cancer.

PMID- 24095299
TI  - Two schedules of etirinotecan pegol (NKTR-102) in patients with previously
      treated metastatic breast cancer: a randomised phase 2 study.
AB  - BACKGROUND: New therapeutic options are needed for patients with heavily
      pretreated breast cancer. Etirinotecan pegol is a long-acting topoisomerase-I
      inhibitor designed to provide prolonged tumour-cell exposure to SN38, the active
      metabolite. We aimed to assess the efficacy and safety of two etirinotecan pegol
      dosing schedules in patients with previously treated metastatic breast cancer to
      determine an optimum dosing schedule for phase 3 trials. METHODS: In this
      randomised, two-stage, open-label phase 2 trial, we recruited patients aged 18
      years or older who had received taxane therapy and undergone two or fewer
      previous chemotherapy regimens for metastatic breast cancer, with an Eastern
      Cooperative Oncology Group performance status of 0 or 1, from 18 sites in three
      countries. Eligible patients were randomly assigned (1:1) to etirinotecan pegol
      145 mg/m(2) every 14 days or every 21 days. The primary endpoint was the
      proportion of patients with a confirmed objective response as defined by Response
      Evaluation Criteria in Solid Tumors version 1.0, analysed by intention to treat.
      Safety was assessed in all patients who received at least one dose of study drug.
      FINDINGS: 70 patients (35 in each group) were randomly assigned to treatment
      between Feb 17, 2009 and April 13, 2010. Of the 70 patients, 20 (29%; 95% CI 18.4
      40.6) achieved an objective response (two [3%] had a complete response and 18
      [26%] had a partial response). Ten patients on the 14-day schedule achieved an
      objective response (29%; 95% CI 14.6-46.3; eight partial responses, two complete
      responses) as did ten on the 21-day schedule (29%; 95% CI 14.6-46.3; all partial
      responses). The most common grade 3 or worse adverse events were delayed
      diarrhoea (seven [20%] of 35 patients on the 14-day schedule vs eight [23%] of 35
      patients on the 21-day schedule), fatigue (five [14%] vs three [9%]), neutropenia
      (four [11%] vs four [11%]), and dehydration (three [9%] vs four [11%]); 14 [20%]
      patients discontinued treatment because of drug-related toxicity. There were two
      possible drug-related deaths (acute renal failure and septic shock) in the 14-day
      group; other drug-related serious adverse events reported by more than one
      patient included ten [14%] patients with diarrhoea (six [17%] patients on the 14
      day schedule vs four [11%] on the 21-day schedule), six [9%] with dehydration
      (two [6%] vs four [11%]), two [3%] with nausea (two [6%] vs none), and two [3%]
      with vomiting (two [6%] vs none). INTERPRETATION: On the basis of the overall
      clinical data, pharmacokinetics, and tolerability profile, etirinotecan pegol 145
      mg/m(2) every 21 days has been selected for a phase 3 trial against treatment of
      physician's choice in patients with advanced breast cancer.

PMID- 24095300
TI  - Lapatinib as a component of neoadjuvant therapy for HER2-positive operable breast
      cancer (NSABP protocol B-41): an open-label, randomised phase 3 trial.
AB  - BACKGROUND: We studied the effect on tumour response to neoadjuvant therapy of
      the substitution of lapatinib for trastuzumab in combination with weekly
      paclitaxel after doxorubicin plus cyclophosphamide treatment, and of the addition
      of lapatinib and trastuzumab combined after doxorubicin plus cyclophosphamide
      treatment in patients with HER2-positive operable breast cancer to determine
      whether there would be a benefit of dual HER2 blockade in these patients.
      METHODS: For this open-label, randomised phase 3 trial we recruited women aged 18
      years or older with an ECOG performance status of 0 or 1 with operable HER2
      positive breast cancer. Each received four cycles of standard doxorubicin 60
      mg/m(2) and cyclophosphamide 600 mg/m(2) intravenously on day 1 every 3 weeks
      followed by four cycles of weekly paclitaxel (80 mg/m(2)) intravenously on days
      1, 8, and 15, every 4 weeks. Concurrently with weekly paclitaxel, patients
      received either trastuzumab (4 mg/kg load, then 2 mg/kg intravenously) weekly
      until surgery, lapatinib (1250 mg orally) daily until surgery, or weekly
      trastuzumab plus lapatinib (750 mg orally) daily until surgery. After surgery,
      all patients received trastuzumab to complete 52 weeks of HER2-targeted therapy.
      Randomisation (ratio 1:1:1) was done centrally with stratification by clinical
      tumour size, clinical nodal status, hormone-receptor status, and age. The primary
      endpoint was the pathological complete response in the breast, and analysis was
      performed on an intention-to-treat population. FINDINGS: Patient accrual started
      on July 16, 2007, and was completed on June 30, 2011; 529 women were enrolled in
      the trial. 519 patients had their pathological response determined. Breast
      pathological complete response was noted in 93 (52.5%, 95% CI 44.9-59.5) of 177
      patients in the trastuzumab group, 91 (53.2%, 45.4-60.3) of 171 patients in the
      lapatinib group (p=0.9852); and 106 (62.0%, 54.3-68.8) of 171 patients in the
      combination group (p=0.095). The most common grade 3 and 4 toxic effects were
      neutropenia (29 [16%] patients in the trastuzumab group [grade 4 in five patients
      (3%), 28 [16%] in the lapatinib group [grade 4 in eight patients (5%)], and 29
      [17%] in the combination group [grade 4 in nine patients (5%)]) and grade 3
      diarrhoea (four [2%] patients in the trastuzumab group, 35 [20%] in the lapatinib
      group, and 46 [27%] in the combination group; p<0.0001). Symptomatic congestive
      heart failure defined as New York Heart Association Class III or IV events
      occurred in seven (4%) patients in the trastuzumab group, seven (4%) in the
      lapatinib group, and one (<1%) in the combination group; p=0.185).
      INTERPRETATION: Substitution of lapatinib for trastuzumab in combination with
      chemotherapy resulted in similar high percentages of pathological complete
      response. Combined HER2-targeted therapy produced a numerically but
      insignificantly higher pathological complete response percentage than single
      agent HER2-directed therapy; these findings are consistent with results from
      other studies. Trials are being undertaken to further assess these findings in
      the adjuvant setting.

PMID- 24095301
TI  - [Diagnostic laparoscopy in gynecological cancer, prophylactic oophorectomy:
      feasibility study on 22 cases].
AB  - OBJECTIVES: The purpose of our study was to assess the feasibility of outpatient
      laparoscopy in a cohort of 22 patients admitted for bilateral oophorectomy (n=11)
      and preoperative diagnostic laparoscopy (n=11). PATIENTS AND METHODS: Between
      December 2012 and May 2013, we included 22 patients in our study. All selected
      patients received a questionnaire the day before surgery. The questionnaire
      consisted of chapters on intraoperatively, and the postoperative assessments of
      patients regarding a possible return home on the evening of surgery. The ability
      to output was measured with the score of Chung at the evening of surgery and in
      the morning before leaving. RESULTS: The mean age of patients was 60 years. The
      average length of stay was 1.2 days. Postoperative pain tends to be higher in the
      morning in the bilateral oophorectomy group (P=0.06), nausea and vomiting are the
      same in both groups. In the bilateral oophorectomy group, six patients were able
      to go out and five wished it; in the diagnostic laparoscopy group nine patients
      were able to go out and two wished it, this difference was significant (P=0.041).
      DISCUSSION: The outpatient hospital is the norm for many surgeries. In our study,
      47% of patients able to go out wishing that output. This difference is important
      when comparing the two groups. There are more patients wishing an output in the
      oophorectomy group. This reduction in length of stay must be compensated by a
      medical and paramedical supervision at home. CONCLUSION: A large number of
      surgical procedure are performed on an outpatient basis. Patients who underwent
      diagnostic laparoscopy are more fragile, they should receive active postoperative
      support to enable an outpatient hospital.

PMID- 24095302
TI  - Identifying the intergenerational effects of the 1959-1961 Chinese Great Leap
      Forward Famine on infant mortality.
AB  - Using the 1959-1961 Chinese Great Leap Forward Famine as a natural experiment,
      this study examines the relationship between mothers' prenatal exposure to acute
      malnutrition and their children's infant mortality risk. According to the
      results, the effect of mothers' prenatal famine exposure status on children's
      infant mortality risk depends on the level of famine severity. In regions of low
      famine severity, mothers' prenatal famine exposure significantly reduces
      children's infant mortality, whereas in regions of high famine severity, such
      prenatal exposure increases children's infant mortality although the effect is
      not statistically significant. Such a curvilinear relationship between mothers'
      prenatal malnutrition status and their children's infant mortality risk is more
      complicated than the linear relationship predicted by the original fetal origins
      hypothesis but is consistent with the more recent developmental origins of health
      and disease theory. 

PMID- 24095303
TI  - RNA-dependent DNA endonuclease Cas9 of the CRISPR system: Holy Grail of genome
      editing?
AB  - Tailor-made nucleases for precise genome modification, such as zinc finger or
      TALE nucleases, currently represent the state-of-the-art for genome editing.
      These nucleases combine a programmable protein module which guides the enzyme to
      the target site with a nuclease domain which cuts DNA at the addressed site.
      Reprogramming of these nucleases to cut genomes at specific locations requires
      major protein engineering efforts. RNA-guided DNA endonuclease Cas9 of the type
      II (clustered regularly interspaced short palindromic repeat) CRISPR-Cas system
      uses CRISPR RNA (crRNA) as a guide to locate the DNA target and the Cas9 protein
      to cut DNA. Easy programmability of the Cas9 endonuclease using customizable RNAs
      brings unprecedented flexibility and versatility for targeted genome
      modification. We highlight the potential of the Cas9 RNA-guided DNA endonuclease
      as a novel tool for genome surgery, and discuss possible constraints and future
      prospects. 

PMID- 24095304
TI  - Epigenetics and the evolution of virulence.
AB  - A feature of pathogenic and invasive organisms is their adaptability when
      confronted with host and environmental challenges. Recent studies have
      demonstrated that plant pathogens rely on epigenetic processes for this purpose.
      Epiallelic variation of effector genes that results in evasion of host immunity
      is one emerging phenomenon. Another is the epigenetically induced reprogramming
      and diversification of transcriptional patterns by de-repression of transposable
      elements. These observations indicate that epigenetic control of gene expression
      provides a versatile means of generating phenotypic diversity that is adaptable
      and heritable across generations. 

PMID- 24095305
TI  - HPV genotyping in adenocarcinoma of the uterine cervix in Thailand.
AB  - OBJECTIVE: To determine the distribution of human papillomavirus (HPV) genotypes
      in cervical adenocarcinoma in Thailand and to evaluate the clinicopathologic
      characteristics associated with common HPV genotypes. METHODS: Formalin-fixed,
      paraffin-embedded tissues from 150 patients with adenocarcinoma were collected
      from 4 areas of Thailand. Infection with HPV was detected by nested polymerase
      chain reaction (PCR) with primers MY09/11 and GP5+/6+. Genotyping was performed
      using a linear array assay, followed by type-specific PCR targeting the E6/E7
      regions of HPV-16, HPV-18, and HPV-52 if the linear array test was negative.
      RESULTS: Human papillomavirus DNA was detected in 145 (97%) adenocarcinomas (132
      single infections; 11 multiple infections; 2 tumors with undetermined HPV type).
      Genotype 18 was most common (66%), followed by HPV-16 (30%) and HPV-45 (3%).
      Infection with only HPV-16 and/or HPV-18 accounted for 88% of the HPV-positive
      tumors. Patients with HPV-18 infection had a younger age (P=0.009) and higher
      tumor grade (P<0.001) than patients with HPV-16 infection. CONCLUSION: The HPV
      detection rate in cervical adenocarcinomas in Thailand is high. The predominant
      genotype is HPV-18, being twice as common as HPV-16. Genotype variations are
      associated with patient age and tumor grade. Vaccination against HPV-16/HPV-18
      might prevent almost 90% of adenocarcinomas.

PMID- 24095306
TI  - Discrepancies between clinicians and rural healthcare workers regarding referral
      procedures based on blood pressure measurements.

PMID- 24095307
TI  - Promoters of and barriers to cervical cancer screening in a rural setting in
      Tanzania.
AB  - OBJECTIVE: To investigate promoters and barriers for cervical cancer screening in
      rural Tanzania. METHODS: We interviewed 300 women of reproductive age living in
      Kiwangwa village, Tanzania. The odds of attending a free, 2-day screening service
      were compared with sociodemographic variables, lifestyle factors, and knowledge
      and attitudes surrounding cervical cancer using multivariable logistic
      regression. RESULTS: Compared with women who did not attend the screening service
      (n=195), women who attended (n=105) were older (OR 4.29; 95% CI, 1.61-11.48, age
      40-49years versus 20-29years), listened regularly to the radio (OR 24.76; 95% CI,
      11.49-53.33, listened to radio 1-3 times per week versus not at all), had a
      poorer quality of life (OR 4.91; CI, 1.96-12.32, lowest versus highest score),
      had faced cost barriers to obtaining health care in the preceding year (OR 2.24;
      95% CI, 1.11-4.53, yes versus no), and held a more positive attitude toward
      cervical cancer screening (OR 4.64; 95% CI, 1.39-15.55, least versus most
      averse). CONCLUSION: Efforts aimed at improving screening rates in rural Tanzania
      need to address both structural and individual-level barriers, including
      knowledge and awareness of cervical cancer prevention, cost barriers to care, and
      access to health information.

PMID- 24095308
TI  - Prevalence, characteristics, and outcomes of HIV-positive women diagnosed with
      invasive cancer of the cervix in Kenya.
AB  - OBJECTIVE: To determine the prevalence of invasive cervical cancer (ICC) and
      assess access to, and outcomes of, treatment for ICC among HIV-infected women in
      Kisumu, Kenya. METHODS: We performed a retrospective chart review to identify
      women diagnosed with ICC between October 2007 and June 2012, and to examine the
      impact of a change in the referral protocol. Prior to June 2009, all women with
      ICC were referred to a regional hospital. After this date, women with stage IA1
      disease were offered treatment with loop electrosurgical excision procedure
      (LEEP) in-clinic. RESULTS: Of 4308 women screened, 58 (1.3%) were diagnosed with
      ICC. The mean age at diagnosis was 34years (range, 22-50years). Fifty-four
      (93.1%) women had stage IA1 disease, of whom 36 (66.7%) underwent LEEP, 7 (12.9%)
      had a total abdominal hysterectomy, and 11 (20.4%) had unknown or no treatment.
      At 6, 12, and 24months after LEEP, 8.0% (2/25), 25.0% (6/24), and 41.2% (7/17) of
      women had a recurrence of cervical intraepithelial neoplasia 2 or worse,
      respectively. CONCLUSION: Most HIV-positive women diagnosed with ICC through
      screening had early-stage disease. The introduction of LEEP in-clinic increased
      access to treatment; however, recurrence was high, indicating the need for
      continued surveillance.

PMID- 24095309
TI  - The effect of midwifery care on rates of cesarean delivery.
AB  - OBJECTIVE: To examine whether changing to a midwifery-led maternity service model
      was associated with a lower national rate of cesarean delivery. METHODS: We
      analyzed trends in the rate of cesarean delivery per 1000 live births between
      1996 and 2010 in New Zealand. Estimates of relative increases in rate were
      calculated via Poisson regression for several maternal age groups over the study
      period. RESULTS: Rates of cesarean delivery increased over the study period, from
      156.9 per 1000 live births in 1996 to 235 per 1000 in 2010: a crude increase of
      49.8%. Increasing trends were apparent in each age group, with the largest
      increases occurring before 2003 and relatively stable rates in the subsequent
      period. The smoothed estimate showed that the increase in cesarean rate across
      all age groups was 43.7% (95% confidence interval, 41.6-45.8) over the 15-year
      period. CONCLUSION: A national midwifery-led care model was not associated with a
      decreased rate of cesarean delivery but, instead, with an increase similar to
      that in other high-resource countries. This indicates that other factors may
      account for the increase. Further research is needed to examine maternity
      outcomes associated with different models of maternity care.

PMID- 24095310
TI  - Medicolegal aspects of complex behaviours arising from the sleep period: a review
      and guide for the practising sleep physician.
AB  - This review is aimed at summarizing the current state of knowledge regarding
      parasomnias, which have been implicated in medicolegal cases as well as providing
      guidance to those working within common-law jurisdictions regarding the technical
      aspects of the law. Sleepwalking and sexsomnia as a defence are being raised more
      frequently in criminal cases and there has been public debate on their validity.
      Unfortunately, expert evidence on forensic sleep disorders continues to be
      heavily opinion-based with the potential for miscarriages of justice seen in
      recent highly publicized cases. There is an apparent inertia in research into
      violent sleep disorders. We review the current state of forensic sleep science in
      the United Kingdom (UK) and abroad and discuss the need to formulate guidelines
      based on available evidence. We also highlight the pressing necessity for more
      research in this area as well as the need to reform the law, which is the subject
      of a recent Criminal Law Commission report in the United Kingdom. In time, this
      will facilitate the efficient, proportionate, and just disposal of violence
      arising from sleep, thus benefitting both society and the individual sufferer. 

PMID- 24095566
TI  - Myofibroblastic tumor of epididymis.

PMID- 24095567
TI  - [Endoscopic approach to ventricular atrium for biopsy of pineal region tumour:
      case report].
AB  - INTRODUCTION: The usual endoscopic approach in the management of pineal region
      tumours consists of inserting the scope into the frontal horn of the lateral
      ventricle and advancing it through the foramen of Monro into the third ventricle.
      We report the case of a patient with a pineal tumour on whom we used an
      endoscopic approach through the ventricular atrium to obtain a biopsy by opening
      the choroidal fissure. CLINICAL CASE: This young 25-year-old man presented with
      headache and double vision. Papilloedema and Parinaud's syndrome were found on
      physical examination. Cranial magnetic resonance revealed a pineal mass and
      hydrocephalus. We initially performed a third ventriculostomy and a tumour biopsy
      through a frontal burr hole. The tissue sample was not useful for pathological
      diagnosis and we decided to perform a second endoscopic biopsy. CONCLUSIONS: The
      endoscopic approach to pineal region masses, reaching the ventricular atrium
      through a parietal burr hole and opening the choroidal fissure, makes it possible
      to take a biopsy using a single endoscopic approach without needing to cross
      other ventricular structures.

PMID- 24095568
TI  - Stability of genotyping target sequences of Mycobacterium avium subsp.
      paratuberculosis upon cultivation on different media, in vitro- and in vivo
      passage, and natural infection.
AB  - Mycobacterium (M.) avium subsp. paratuberculosis - the causative agent of
      paratuberculosis (Johne's disease) - affects domestic and wild ruminants
      worldwide. Recently, different typing techniques have been combined to provide
      sufficient discriminatory power for the differentiation of isolates and for
      epidemiological studies. In order to challenge the reliability of this approach
      the stability of different M. avium subsp. paratuberculosis genotypes determined
      after primary isolation was investigated after sub-cultivation on six different
      media (A), twelve in vitro passages (B), or a singular in vivo passage (C). In
      addition, different isolates from a single animal or herd were investigated (D).
      Sub-cultures of type- and reference strains, re-isolated inoculation strain after
      in vivo passage, and 23 field isolates were genotyped by mycobacterial
      interspersed repetitive unit-variable-number of tandem-repeat (MIRU-VNTR)-, short
      sequence-repeat (SSR)-, and IS900-based restriction-fragment length-polymorphism
      (IS900-RFLP)-analyses and compared with initial genotypes. MIRU-VNTR-alleles (at
      loci 292, X3, 25, 47, 7, and 32) were stable after in vitro cultivations and
      after animal passage. Results of SSR analysis at Locus 1 with 7G nucleotides and
      at Loci 8 and 9 (tri-nucleotides) were also stable. At Locus 2 9G repeats changed
      into 10G after goat passage. After in vitro subculture (A+B) but not after animal
      passage (C) IS900-RFLP-typing revealed changes of BstEII-patterns for 3 of 23
      strains (including ATCC 19698). Multiple isolates from individual animals or from
      a single cattle herd with natural infection (D) which exhibited identical IS900
      RFLP- and MIRU-VNTR- genotypes, showed different G repeat numbers at SSR locus 2.
      This implies strand slippage events during chromosomal duplication of bacteria in
      the course of bacterial spreading within hosts and herds. Consequently, SSR-Locus
      2 is not suitable as genome marker for epidemiological studies. 

PMID- 24095569
TI  - Investigation of the koala (Phascolarctos cinereus) hindgut microbiome via 16S
      pyrosequencing.
AB  - As a dietary source, the foliage of Eucalyptus spp. is low in available protein
      and carbohydrate while containing polyphenolic compounds that interfere with
      enzymatic digestion. To overcome this, the koala (Phascolarctos cinereus) has
      evolved a range of anatomical and physiological adaptations to assist with
      digestion and absorption of nutrients from this food source. Microbial
      fermentation of partially digested eucalyptus leaves is thought to be critical in
      this process, however, little is known about the composition and diversity of
      microorganisms that are associated with digestive health in this native species.
      In this study, we performed 16S rRNA gene pyrosequencing of caecum, colon and
      faecal pellet samples from two wild, free ranging, Queensland koalas. Our results
      reveal a highly complex and diverse ecosystem with considerable intra-individual
      variation. Although samples were dominated by sequences from the Bacteroidetes
      and Firmicutes phyla there was considerable variation at the genus level. This
      study is the first non-culture based microbiota analysis, using 454-amplicon
      pyrosequencing, and provides preliminary data to expand our understanding of the
      koala hindgut. 

PMID- 24095570
TI  - Multistage approach for clustering and classification of ECG data.
AB  - Accurate and fast approaches for automatic ECG data classification are vital for
      clinical diagnosis of heart disease. To this end, we propose a novel multistage
      algorithm that combines various procedures for dimensionality reduction,
      consensus clustering of randomized samples and fast supervised classification
      algorithms for processing of the highly dimensional large ECG datasets. We
      carried out extensive experiments to study the effectiveness of the proposed
      multistage clustering and classification scheme using precision, recall and F
      measure metrics. We evaluated the performance of numerous combinations of various
      methods for dimensionality reduction, consensus functions and classification
      algorithms incorporated in our multistage scheme. The results of the experiments
      demonstrate that the highest precision, recall and F-measure are achieved by the
      combination of the rank correlation coefficient for dimensionality reduction,
      HBGF consensus function and the SMO classifier with the polynomial kernel. 

PMID- 24095571
TI  - MRI findings in infants with infantile spasms after neonatal hypoxic-ischemic
      encephalopathy.
AB  - BACKGROUND: To evaluate the predominant pattern of brain injury and the anatomic
      areas of injury in children with infantile spasms following neonatal hypoxic
      ischemic encephalopathy. METHODS: A nested case-control study of infantile spasms
      in children with term neonatal hypoxic-ischemic encephalopathy was performed. All
      patients had T1/T2-weighted magnetic resonance imaging with diffusion-weighted
      imaging performed on the third day of life. Using a validated scoring system, the
      magnetic resonance imaging was classified as: normal, watershed, basal
      ganglia/thalamus, total, or focal-multifocal. Two study investigators scored
      additional anatomic areas of injury (cortical extent, levels of the brainstem,
      hypothalamus) on T1/T2-weighted magnetic resonance imaging and diffusion-weighted
      imaging blinded to the outcome. The predominant pattern of brain injury and
      anatomic areas of injury were compared between patients who developed infantile
      spasms and randomly selected controls. RESULTS: Eight patients who developed
      infantile spasms were identified among a cohort of 176 term newborns with hypoxic
      ischemic encephalopathy (4.5%). There were no significant differences in the
      perinatal and neonatal course between newborns who developed infantile spasms and
      controls who did not. The development of infantile spasms after neonatal hypoxic
      ischemic encephalopathy was significantly associated with basal ganglia/thalamus
      and total brain injury (P = 0.001), extent of cortical injury greater than 50%
      (odds ratio = 11.7, 95% confidence interval = 1.1-158.5, P = 0.01), injury to the
      midbrain (odds ratio = 13, 95% confidence interval = 1.3-172, P = 0.007) and
      hypothalamic abnormalities (P = 0.01). CONCLUSIONS: The development of infantile
      spasms after hypoxic-ischemic encephalopathy is associated with injury to the
      basal ganglia and thalami on neonatal magnetic resonance imaging, particularly
      when extensive cortical injury and/or injury to the midbrain is present.

PMID- 24095572
TI  - A germ cell tumor masquerading as Bell palsy.

PMID- 24095573
TI  - Access to neuropsychologic services after pediatric brain tumor.
AB  - BACKGROUND: Increasing survival rates for children with brain tumors creates a
      greater need for neuropsychologic follow-up and intervention. The aim of this
      study was to evaluate rates of referral by medical doctors to neuropsychologic
      services and patient and treatment factors that differentiated referred and
      nonreferred patients. METHODS: Data were retrieved from medical records of all
      pediatric brain tumor patients in southern Sweden diagnosed between 1993 and 2004
      who survived more than 1 year (n = 132). Characteristics of the patients, the
      cancer, and treatment received were then compared for patients who were and were
      not referred for neuropsychologic examination during that period. RESULTS: Sixty
      four (48%) of the pediatric brain tumor patients were referred for
      neuropsychologic evaluation. These patients had significantly larger tumors, more
      recurrences of cancer, and increased intracranial pressure at diagnosis when
      compared with the nonreferred group (n = 68). However, most of the patients in
      the nonreferred group either had significant risk factors for cognitive
      impairment or were reporting impairments that would suggest a referral was
      warranted. CONCLUSIONS: Given the high rates of cognitive impairment in children
      with brain tumors, referral to neuropsychologic services should be considered in
      all survivors. In addition to improving long-term adjustment, systematic referral
      can provide data on cognitive impairments, making it possible to evaluate
      different cancer treatment protocols not only in terms of survival but also in
      terms of quality of survival. Greater efforts are needed to disseminate and raise
      awareness about published guidelines on the long-term care of pediatric brain
      tumor patients.

PMID- 24095574
TI  - Cerebellar mutism and reversible cytotoxic edema in influenza B-associated
      encephalopathy.
AB  - BACKGROUND: Influenza virus-associated neurological complications are rare,
      though well-documented, especially in children. Encephalopathy and seizures are
      the most common complications and are typically associated with influenza A
      infection. Cerebellar mutism has been rarely reported in association with
      influenza B infection. PATIENT: We describe a 3-year-old boy who presented with
      cough, fever, altered mental status, seizure, hypotonia, and mutism. He tested
      positive for influenza B virus. His brain magnetic resonance imaging showed
      reversible cytotoxic edema limited to the middle cerebellar peduncles and the
      dentate nuclei. Other viral, vascular, toxic, and metabolic causes were ruled
      out. CONCLUSION: Our patient represents a case of cerebellar mutism associated
      with influenza B encephalopathy in which the brain magnetic resonance imaging
      scan showed reversible cytotoxic edema limited to the middle cerebellar peduncles
      and the dentate nuclei. This clinicoradiological correlation supports other
      reports in which the dentate nuclei play a major rule in the pathogenesis of
      cerebellar mutism.

PMID- 24095575
TI  - Partial PLP1 deletion causing X-linked dominant spastic paraplegia type 2.
AB  - BACKGROUND: Proteolipid protein 1 gene (PLP1) mutations result in a continuum of
      neurological findings characterized by X-linked hypomyelinating leukodystrophies
      of the central nervous system, from mild spastic paraplegia type 2 to severe
      Pelizaeus-Merzbacher disease. PATIENTS: We report spastic paraplegia type 2 in
      three individuals in one family. A 29-year-old man developed progressive spastic
      quadriplegia from early childhood with dysarthria, ataxia, dysphagia, and
      intellectual delay, but he displayed no nystagmus. His mother developed adult
      onset mild spastic diplegia with dementia developing in later life, whereas his
      sister exhibited spastic diplegia from childhood, complicated by motor
      developmental delay and dysphagia. All three individuals had initially mild but
      progressive neurological phenotypes, no nystagmus, normal brainstem auditory
      evoked potentials, and demyelinating peripheral neuropathy, but with varying
      clinical severity. RESULTS: A 33-kb deletion encompassing exon 2 to 7 of PLP1 was
      identified in all three patients. Cloning of the junction fragment of the genomic
      recombination revealed a short palindromic sequence at the distal breakpoint,
      potentially facilitating a double-strand deoxyribonucleic acid break, followed by
      nonhomologous end joining. X-inactivation study and sequencing of the undeleted
      PLP1 alleles failed to explain the differences in severity between the two female
      patients. CONCLUSIONS: PLP1 partial deletion is a rare cause of spastic
      paraplegia type 2 and exhibits X-linked dominant inheritance with variable
      expressivity.

PMID- 24095576
TI  - Limbic encephalitis in a child: an atypical presentation.
AB  - BACKGROUND: Limbic encephalitis is a rare disorder with a generally subacute
      onset evolving over days to weeks. Patients present with a variable combination
      of memory loss, seizures, and psychiatric disturbance, and it is not rare for
      patients to be initially misdiagnosed. PATIENT: We describe a previously healthy
      12-year-old boy who developed his first seizures at 8 years of age. He had a
      total of eight prolonged focal seizures, each followed by a month of behavioral
      changes and short-term memory loss. There was no family history of seizures or
      other neurological disorders, and he had an otherwise unremarkable neonatal and
      medical history. RESULTS: Magnetic resonance imaging during each episode of
      seizures showed alternating unilateral brain hemispheric involvement consistent
      with limbic encephalitis that was followed by resolution for a total of six
      times. Despite a negative laboratory evaluation for a large panel of
      paraneoplastic antibodies, the clinical scenario and exclusion of other possible
      disorders made recurrent limbic encephalitis the most likely diagnosis.
      CONCLUSION: Limbic encephalitis is a rare disorder that is diagnosed primarily on
      the basis of clinical criteria and is often associated with the presence of a
      paraneoplastic antibody. However, lack of a positive paraneoplastic antibody in a
      patient with a triad of seizure, behavioral changes, and short-term memory loss
      does not exclude the diagnosis. The unique presentation in a seronegative patient
      may indicate an unrecognized antibody.

PMID- 24095577
TI  - Social behavior and comorbidity in children with tics.
AB  - OBJECTIVES: To examine the characteristics of children with coexisting tics and
      autism spectrum disorder and determine if children with tics have deficits in
      social behavior. METHODS: Descriptive study of children referred for tics over 18
      months. Parents completed the Social Responsiveness Scale and the Social
      Communications Questionnaire; children screening positive on these measures were
      evaluated for autism spectrum disorder. Characteristics of children who were
      diagnosed with both disorders are described. Subscales scores on the Social
      Responsiveness Scale for children with tics without a comorbid autism spectrum
      disorder were compared. The relationship between a comorbid diagnosis of
      attention deficit hyperactivity disorder and autism spectrum disorder symptoms
      was explored using logistic and linear regression. RESULTS: One hundred and
      fourteen children were evaluated. Children with a tic disorder and autism
      spectrum disorder had significantly higher rates of comorbid attention deficit
      hyperactivity disorder (P = 0.005), rage attacks (P = 0.006), and oppositional
      defiant disorder (P = 0.007) than children without autism spectrum disorder. Mean
      tic severity and treatment rates did not differ between groups. Mean subscale
      scores on the Social Responsiveness Scale for children without autism spectrum
      disorders fell into the clinically significant range for autistic mannerisms
      only. All Social Responsiveness Scale scores were significantly increased by an
      attention deficit hyperactivity disorder diagnosis (P < 0.0001). CONCLUSION:
      Children referred for assessment of tics should be screened for autism spectrum
      disorders. There is a subgroup of children with multiple neuropsychiatric
      comorbidities who suffer from social dysfunction and autistic mannerisms outside
      of an autism spectrum disorder diagnosis.

PMID- 24095578
TI  - White matter lesions in children and adolescents with migraine.
AB  - BACKGROUND: The etiology and clinical importance of white matter lesions in
      migraine remain poorly understood. To understand these issues more fully, we
      reviewed the brain magnetic resonance imaging scans of pediatric patients and
      assessed the relationships between white matter lesions, migraine type, patent
      foramen ovale, and right-to-left shunting. METHODS: The magnetic resonance
      imaging scans of a cohort of children (n = 89) and adolescents, ages 6 to 18
      years, who participated in a study of migraine and patent foramen ovale were
      reviewed. All children in the cohort had undergone saline contrast transthoracic
      echocardiography and transcranial Doppler studies. RESULTS: White matter lesions
      were detected in 15 of the 89 patients (17%). White matter lesions were small (<5
      mm) in the majority (10/15; 66%). We observed no relationship between the
      presence of white matter lesions and (1) migraine type (six patients with white
      matter lesions among 35 with migraine with aura [17%] vs. nine with white matter
      lesions among 54 without aura [17%]; P = 1.0); (2) patent foramen ovale (five
      with white matter lesions among 35 with patent foramen ovale [14%] vs. 10 with
      white matter lesions among 54 without patent foramen ovale [19%]; P = 0.77); or
      (3) shunt size (two large shunts in 15 with white matter lesions [13%] vs. nine
      large shunts among 72 without white matter lesions [13%]; P = 1.0). CONCLUSIONS:
      These results indicate that small white matter lesions are not infrequent in
      children and adolescents with migraine. However, no relationships between white
      matter lesions and migraine type, patent foramen ovale, or degree of right-to
      left shunting were observed.

PMID- 24095583
TI  - Recovery of natural killer cells and prognosis after cord blood transplantation.
AB  - The relationship between immune reconstitution and the prognosis after cord blood
      transplantation is unclear. We investigated the influence of natural killer (NK)
      cell recovery on transplant outcomes. The maximum number of CD56+CD3- cells or
      CD57+CD16+ cells was determined to assess NK recovery. Although the high CD56+CD3
      group and high CD57+CD16+ group showed significantly better overall survival
      (OS) than the low group on univariate analysis, the high CD57+CD16+ group was
      associated with better OS on multivariate analysis. These results suggest that
      CD57+CD16+ cell recovery is more closely related to the outcome after CBT than
      CD56+CD3- cell recovery. 

PMID- 24095584
TI  - Income and outcome in myelodysplastic syndrome: the prognostic impact of SES in a
      single-payer system.
AB  - We examined the prognostic impact of SES, estimated by census median household
      income, in 312 adult MDS patients. Age, progression to AML, use of recombinant
      erythropoietin, WHO diagnosis and IPSS risk category were independent predictors
      of survival but there was no association between SES and survival. Unexpectedly,
      progression to AML was more prevalent in the highest income quartile (HR 3.96 for
      highest vs. lowest; p=0.0032). The previously demonstrated association of low SES
      with poor outcome MDS in the United States may have been driven primarily by
      reduced access to care rather than other SES-linked factors such as co-morbidity.

PMID- 24095585
TI  - Subtrochanteric shortening in total hip arthroplasty: biomechanical comparison of
      four techniques.
AB  - Safe reduction of the femoral head into the true acetabulum requires a certain
      amount of femoral shortening in patients with high dislocation of the hip. In
      subtrochanteric shortening applications, to reduce complications it is necessary
      to maintain a stable fixation at the osteotomy line. The purpose of this study is
      to investigate frequently used methods from a biomechanical point of view. Four
      osteotomy groups were created with composite femurs to investigate
      subtrochanteric osteotomies; transverse, oblique, z-subtrochanteric and double
      Chevron. All loading tests were carried out with two implant types both with and
      without strut graft and cable fixation. No single inherent feature increasing the
      stability of the investigated osteotomy types was found. Additionally graft
      application did not have a significant contribution to stability. 

PMID- 24095586
TI  - Topical tranexamic acid reduces transfusion rates in total hip and knee
      arthroplasty.
AB  - The efficaciousness of topical tranexamic acid use at the end of knee
      arthroplasty surgery to reduce blood loss and transfusion requirements has
      previously been shown. The aim of this study was to retrospectively assess the
      effectiveness of topical tranexamic acid use, comparing 155 patients undergoing
      hip and knee arthroplasty surgery in which tranexamic acid was routinely used, to
      a group of 149 patients from a similar time frame prior to the introduction of
      tranexamic acid use. The transfusion rate fell from 19.3% to 2.3% for hip
      arthroplasty patients and from 13.1% to 0% for knee arthroplasty patients; these
      differences were significant. We also found significant reductions in haemoglobin
      loss, blood loss and length of stay of 8 g/L, 244 mL and 1.0 days respectively
      for hip arthroplasties and 15 g/L, 527 mL and 1.2 days respectively for knee
      arthroplasties following the introduction of tranexamic acid.

PMID- 24095587
TI  - Alterations of brain eicosanoid synthetic pathway in multiple sclerosis and in
      animal models of demyelination: role of cyclooxygenase-2.
AB  - Inflammation is a physiological response to exogenous and endogenous stimuli and,
      together with demyelination and immune system activation, is one of the key
      features of multiple sclerosis (MS). Arachidonic acid (AA) metabolism by
      cyclooxygenase (COX) and lipoxygenase (LO) enzymes leads to the production of
      proinflammatory eicosanoids, and stimulates cytokine production and activation of
      microglia and astrocytes, thereby contributing to MS pathology. Current therapies
      target the immune system but do not specifically target AA-related inflammatory
      pathway. Corticosteroids and non-steroidal anti-inflammatory drugs (NSAIDs) are
      frequently associated with immunomodulatory therapies to treat flu-like adverse
      effects. Few clinical and mounting preclinical data in MS show that AA metabolism
      contributes to immune system activation, demyelination and motor disabilities,
      and administration of NSAIDs reduces these symptoms. The beneficial effect of
      NSAIDs seems to be a prerogative of COX-2 selective inhibitors and suggests that
      NSAIDs selective for COX-2 may be more effective than mixed COX-1/2 inhibitors. 

PMID- 24095588
TI  - Docosahexaenoic and eicosapentaenoic acid supplementation does not exacerbate
      oxidative stress or intravascular haemolysis in homozygous sickle cell patients.
AB  - We investigated whether or not Omega-3 long-chain polyunsaturated fatty acid
      (omega-3 LCPUFA) supplementation exacerbates oxidative stress in homozygous
      sickle cell patients aged 2 to 14 years. Depending on their age, they received
      between one and three omega-3 (277.8mg DHA and 39.0mg EPA/capsule) or placebo
      (high oleic acid sunflower seed oil) capsules for one year. Supplementation
      increased significantly the levels of the two fatty acids in red cell
      phosphatidylcholine and phosphatidylethanolamine (p<0.001). The patients who
      received omega-3 LCPUFA compared with their placebo-taking counterparts had a
      higher concentration of plasma vitamin E at one year (14.3+/-2.8 versus 12.3+/
      2.8umol/l; p<0.001). The two groups had comparable concentrations of the vitamin
      at six month intervention (10.8+/-2.2 versus 10.7+/-2.9umol/l; p>0.05) and
      baseline (10.7+/-3.1 versus 10.7+/-2.8umol/l; p>0.05). After six month of
      intervention, the patients on omega 3 fatty acids had lower GPx-1 (33.5+/-13.4
      versus 46.6 +/-17.6, p<0.01) and Cu/Zn-SOD (1070+/-600 versus 1470+/-690 p<0.05)
      activities than at baseline. GPx-1 (33.5+/-17.6IU/g Hb versus 43.7+/-13.2IU/g Hb;
      p<0.01) and Cu/Zn-SOD (1070+/-600IU/g Hb versus 1360+/-920IU/g Hb; p>0.05)
      activities were reduced in the omega 3 compared with the placebo at six month
      intervention. There was no difference in the activity of either of the enzymes
      between baseline and six month intervention in the placebo group (p>0.05). This
      study demonstrates; DHA and EPA supplementation, rather than exacerbating the
      inherent oxidative stress associated with the disease, seems to provide an
      antioxidant protection. Hence, it will be safe to provide omega-3 LCPUFA to
      sickle cell patients to help ameliorate vaso-occlusive and haemolytic crises and
      membrane fatty acid abnormality. 

PMID- 24095589
TI  - Response to "MtDNA depletions and deletions may also important in pathogenesis of
      lung cancer".

PMID- 24095590
TI  - Blood lead levels in a representative sample of the Spanish adult population: the
      BIOAMBIENT.ES project.
AB  - This paper provides the first baseline information on a national scale regarding
      lead exposure in the Spanish adult population. Blood lead levels were measured in
      a representative sample of the Spanish working population (1880 subjects aged 18
      65 years) in order to help establish reference levels, follow temporal trends,
      identify high-exposure groups and to enable comparisons with other countries. All
      participants completed an epidemiological questionnaire including gender, age,
      occupational sector, geographic area, and dietary and lifestyle information. We
      found that the geometric mean of blood lead levels in the study population was
      24.0MUg/L (95% CI: 23.0-25.1MUg/L), with women having significantly lower levels
      than men, 19.5MUg/L (18.5-20.5MUg/L) compared to 28.3MUg/L (26.7-30.0MUg/L),
      respectively. Mean blood lead levels were higher in elder groups in both genders.
      Women of a childbearing age had blood levels of 18.0MUg/L (GM). Reference values
      (95%) for lead in blood in the studied population was 56.80MUg/L, with 
      64.00MUg/L, 44.80MUg/L and 36.00MUg/L for man, women and women of childbearing
      age, respectively. Workers from the service sector had lower blood lead levels
      than those from the construction, agricultural and industry sectors. Small,
      although significant, geographical differences had been found. In an European
      comparison, the Spanish population studied herein had lead levels similar to
      populations in countries such as France and Belgium, and slightly lower levels
      than Italian, Czech, German or UK populations. 

PMID- 24095591
TI  - Detection of serum AFB1-lysine adduct in Malaysia and its association with liver
      and kidney functions.
AB  - Aflatoxin is ubiquitously found in many foodstuffs and produced by Aspergillus
      species of fungi. Of many aflatoxin metabolites, AFB1 is classified by the
      International Agency for Research on Cancer (IARC) as group one carcinogen and
      linked to the development of hepatocellular carcinoma (HCC). The study on
      molecular biomarker of aflatoxin provides a better assessment on the extent of
      human exposure to aflatoxin. In Malaysia, the occurrences of aflatoxin
      contaminated foods have been documented, but there is a lack of data on human
      exposure to aflatoxin. Hence, this study investigated the occurrence of AFB1
      lysine adduct in serum samples and its association with liver and kidney
      functions. 5ml fasting blood samples were collected from seventy-one subjects
      (n=71) for the measurement of AFB1-lysine adduct, albumin, total bilirubin, AST
      (aspartate aminotransferase), ALT (alanine transaminase), ALP (alkaline
      phosphatase), GGT (gamma-glutamyl transpeptidase), creatinine and BUN (blood urea
      nitrogen). The AFB1-lysine adduct was detected in all serum samples (100%
      detection rate) with a mean of 6.85+/-3.20pg/mg albumin (range: 1.13-18.85pg/mg
      albumin). Male subjects (mean: 8.03+/-3.41pg/mg albumin) had significantly higher
      adduct levels than female subjects (mean: 5.64+/-2.46pg/mg albumin) (p<0.01). It
      was noteworthy that subjects with adduct levels greater than average (>6.85pg/mg
      albumin) had significantly elevated level of total bilirubin (p<0.01), GGT
      (p<0.05) and creatinine (p<0.01). Nevertheless, only the level of total
      bilirubin, (r=0.347, p-value=0.003) and creatinine (r=0.318, p-value=0.007)
      showed significant and positive correlation with the level of AFB1-lysine adduct.
      This study provides a valuable insight on human exposure to aflatoxin in
      Malaysia. Given that aflatoxin can pose serious problem to the health,
      intervention strategies should be implemented to limit/reduce human exposure to
      aflatoxin. Besides, a study with a big sample size should be warranted in order
      to assess aflatoxin exposure in the general population of Malaysia. 

PMID- 24095592
TI  - Quantitative assessment of infection risk from exposure to waterborne pathogens
      in urban floodwater.
AB  - Flooding and heavy rainfall have been associated with waterborne infectious
      disease outbreaks, however, it is unclear to which extent they pose a risk for
      public health. Here, risks of infection from exposure to urban floodwater were
      assessed using quantitative microbial risk assessment (QMRA). To that aim, urban
      floodwaters were sampled in the Netherlands during 23 events in 2011 and 2012.
      The water contained Campylobacter jejuni (prevalence 61%, range 14- >10(3)
      MPN/l), Giardia spp. (35%, 0.1-142 cysts/l), Cryptosporidium (30%, 0.1-9.8
      oocysts/l), noroviruses (29%, 10(2)-10(4) pdu/l) and enteroviruses (35%, 10(3)
      10(4) pdu/l). Exposure data collected by questionnaire, revealed that children
      swallowed 1.7 ml (mean, 95% Confidence Interval 0-4.6 ml) per exposure event and
      adults swallowed 0.016 ml (mean, 95% CI 0-0.068 ml) due to hand-mouth contact.
      The mean risk of infection per event for children, who were exposed to floodwater
      originating from combined sewers, storm sewers and rainfall generated surface
      runoff was 33%, 23% and 3.5%, respectively, and for adults it was 3.9%, 0.58% and
      0.039%. The annual risk of infection was calculated to compare flooding from
      different urban drainage systems. An exposure frequency of once every 10 years to
      flooding originating from combined sewers resulted in an annual risk of infection
      of 8%, which was equal to the risk of infection of flooding originating from
      rainfall generated surface runoff 2.3 times per year. However, these annual
      infection risks will increase with a higher frequency of urban flooding due to
      heavy rainfall as foreseen in climate change projections.

PMID- 24095593
TI  - Factors affecting the formation of disinfection by-products during chlorination
      and chloramination of secondary effluent for the production of high quality
      recycled water.
AB  - During the production of high quality recycled water by reverse osmosis membrane
      filtration secondary effluent must be disinfected to limit biofouling on the
      membrane surface. Advanced Water Treatment Plants in South East Queensland,
      Australia use disinfectant contact times ranging from 30 min up to 24 h.
      Disinfectants such as chlorine and chloramines react with effluent organic matter
      to generate disinfection by-products (DBPs) which could be potentially hazardous
      to human health if the water is destined for supplementing public water supplies.
      In this context, secondary effluents are of concern because of their high total
      organic carbon content which can act as DBP precursors. Also, effluent organic
      matter may form different DBPs to those formed from natural organic matter during
      conventional drinking water treatment, either in quantity, identity or simply in
      the abundance of different DBPs relative to each other. It cannot be assumed per
      se with certainty that DBP formation will be affected in the same way by
      operational changes as in drinking water production. Response surface modelling
      has been employed in this study at the bench scale to investigate the effect of
      reaction time (0-24 h), pH (5.5-8.5), temperature (23-35  degrees C),
      disinfection strategy (chlorine vs chloramines used prior to membrane treatment)
      and the interaction between these different parameters on DBP formation during
      disinfection of secondary effluent. The concentration of halogenated DBPs formed
      during the first 24 h of reaction with the different disinfectants followed the
      order chlorination >> in line-formed monochloramine > pre-formed monochloramine.
      Contact time with chlorine was the major influencing factor on DBP formation
      during chlorination, except for the bromine-containing trihalomethanes and
      dibromoacetonitrile for which pH was more significant. Chlorination at high pH
      led to an increased formation of chloral hydrate, trichloronitromethane,
      dibromoacetonitrile and the four trihalomethanes while the opposite effect was
      observed for the other targeted DBPs. Temperature was identified as the least
      influencing parameter compared to pH and reaction time for all DBPs in all the
      disinfection strategies, except for the formation of chloral hydrate where pH and
      temperature had a similar significance and bromoform that was similarly affected
      by temperature and reaction time. Chloramines employed at pH 8.5 reduced the
      concentration of all studied DBPs compared to pH 5.5. Furthermore, reaction time
      was the most significant factor for trichloronitromethane, chloroform,
      trichloroacetonitrile, dichloroacetonitrile and bromochloroacetonitrile formation
      while pH was the most influencing factor affecting the formation of the remaining
      DBPs.

PMID- 24095594
TI  - Influence of seasonal and inter-annual hydro-meteorological variability on
      surface water fecal coliform concentration under varying land-use composition.
AB  - Quantifying the influence of hydro-meteorological variability on surface source
      water fecal contamination is critical to the maintenance of safe drinking water.
      Historically, this has not been possible due to the scarcity of data on fecal
      indicator bacteria (FIB). We examined the relationship between hydro
      meteorological variability and the most commonly measured FIB, fecal coliform
      (FC), concentration for 43 surface water sites within the hydro-climatologically
      complex region of British Columbia. The strength of relationship was highly
      variable among sites, but tended to be stronger in catchments with nival
      (snowmelt-dominated) hydro-meteorological regimes and greater land-use impacts.
      We observed positive relationships between inter-annual FC concentration and
      hydro-meteorological variability for around 50% of the 19 sites examined. These
      sites are likely to experience increased fecal contamination due to the projected
      intensification of the hydrological cycle. Seasonal FC concentration variability
      appeared to be driven by snowmelt and rainfall-induced runoff for around 30% of
      the 43 sites examined. Earlier snowmelt in nival catchments may advance the
      timing of peak contamination, and the projected decrease in annual snow-to
      precipitation ratio is likely to increase fecal contamination levels during
      summer, fall, and winter among these sites. Safeguarding drinking water quality
      in the face of such impacts will require increased monitoring of FIB and
      waterborne pathogens, especially during periods of high hydro-meteorological
      variability. This data can then be used to develop predictive models, inform
      source water protection measures, and improve drinking water treatment.

PMID- 24095595
TI  - Solar photo-Fenton like using persulphate for carbamazepine removal from domestic
      wastewater.
AB  - This work aimed at decontaminating biologically treated domestic wastewater
      effluent from pharmaceutical residues by using sulphate radical based homogeneous
      photo-Fenton involving persulphate (PS) as an oxidant, ferrous iron (Fe(II)) as a
      catalyst and simulated solar irradiation as a light source. This is the first
      time that the beneficiary use of solar energy in PS/Fe(II)/UV-Vis system was
      evaluated by using carbamazepine (CBZ) as a probe compound. In wastewater, CBZ
      was fully degraded in 30 min for an initial CBZ concentration of 50 MUM and an
      optimal PS:Fe(II) molar ratio of 2:1 thanks to the high selectivity in reactivity
      of the sulphate radical limiting scavenging effects of organic matter and
      inorganic ions. Seventeen by-products were identified using liquid chromatography
      high resolution-mass spectrometry allowing for the establishment of degradation
      pathways. CBZ first underwent degradation through one electron transfer oxidation
      processes due to sulphate radical reactivity followed by hydroxylation processes
      through hydroxyl radical formed by Fe(III) photoreduction. The sequential
      generation of sulphate radical and hydroxyl radical has made PS/Fe(II)/UV-Vis a
      kinetically effective process in removing CBZ from wastewater without the
      accumulation of toxic intermediates and opens new remediation strategies for
      tertiary treatment in domestic wastewater treatment plants.

PMID- 24095596
TI  - Total elbow arthroplasty for acute distal humeral fractures in patients over 65
      years old - results of a multicenter study in 87 patients.
AB  - INTRODUCTION: Fractures of the distal humerus represent 5% of osteoporosis
      fragility fractures in subjects over the age of 60. Osteoporosis, comorbidities
      and intra-articular comminution make management of this entity difficult.
      HYPOTHESIS: The hypothesis was that total elbow arthroplasty could be a reliable
      treatment option in subjects over the age of 65 presenting with a fracture of the
      distal humerus. MATERIALS AND METHODS: Eight-seven patients (80 women and 7 men)
      mean age 79 years old (65-93) underwent total elbow arthroplasty for the
      treatment of an AO type A fracture in 9 cases, type B in 8 and type C in 70.
      RESULTS: After a mean follow-up of 37.5 months (6-106) the Mayo Elbow Performance
      Score MEPS was 86+/-14, the quick-DASH score was 24+/-19 and the Katz score was
      5+/-1.5 points. The MEPS was better in patients with a high preoperative Katz
      score and a history of inflammatory arthritis who were living at home. Fifty-five
      patients (63%) presented with a pain-free elbow, and 20 (24%) with slight pain.
      The flexion-extension range of motion was 97+/-22 degrees  and 48% presented with
      a flexion-extension arc of at least 100 degrees . Function was normal in 69
      patients. Complications were identified in 20 cases (23%) and revision surgery
      was necessary in 8 (9%). Two arthroplasties had to be changed, one for a fracture
      of the humeral stem component and the other for loosening. Only one infection
      occurred in this series. CONCLUSION: Total elbow arthroplasties provide fractured
      patients with immediate satisfactory results and a stable, painless and
      functional elbow. These results seem to be reliable and durable. The rate of
      complications is low with revision surgery in approximately 10%. LEVEL OF
      EVIDENCE: Level IV.

PMID- 24095597
TI  - Distal targeting device for long Gamma nail((r)). Monocentric observational
      study.
AB  - INTRODUCTION: Intramedullary nail distal locking screws make it possible to
      control length and rotation but include an increased risk of radiation exposure.
      A distal targeting device was recently developed for long Gamma((r)) nails
      (Stryker((r))). The aim of this practical observational study was to evaluate the
      reliability of this system. Our hypothesis was that the targeting device would be
      systematically used without conversion or complications. MATERIALS AND METHODS:
      All of the long Gamma((r)) nails implanted between November 2011 and October 2012
      were recorded: 91 nails (59W/32M, mean age 73.5years old) for 68 traumatic
      fractures, 14 preventive nailings and nine pathological fractures. A junior
      surgeon performed the procedure in 45 cases and a senior in 46 cases. The number
      of times the device was used, the difficulties and complications encountered, the
      duration of fluoroscopy and the dose of radiation were noted. Risk factors were
      looked for. RESULTS: The targeting device was used 79 times (the surgeon chose
      not to use it 11 times, and it was not available in one case). There was a
      measurement error in one case, therefore 78 nails could be evaluated. Three wrong
      positions of the distal locking screw occurred. No statistically significant risk
      factors were identified. Distal locking screw corresponded to 18% of the entire
      procedure at a radiation dose of 7.44% (this was higher with titanium nails and
      pathological fractures). Total fluoroscopy time was longer with junior than with
      senior surgeons but the dose and duration for distal locking were not different.
      DISCUSSION: The hypothesis was not confirmed. The device was not systematically
      used and the risk of complications was not null. No risk factors were identified.
      The distal locking screw is a difficult step but the use of the targeting device
      can limit the dose of radiation. This device is effective and allows young
      surgeons to perform distal locking without increasing the dose of radiation
      compared to senior surgeons. LEVEL OF EVIDENCE: Level IV, cohort study,
      observational prospective follow-up.

PMID- 24095598
TI  - Minimally invasive treatment of displaced intra-articular calcaneal fractures
      using the balloon kyphoplasty technique: preliminary study.
AB  - BACKGROUND: The balloon kyphoplasty approach to the treatment of vertebral
      fractures can be adapted to achieve the reduction and cement stabilisation of
      intra-articular compression fractures at other sites, such as the calcaneus.
      PATIENTS AND METHOD: We studied six patients with a median follow-up of 12 months
      (range, 6-30 months). Fluoroscopy guidance was used to obtain optimal balloon
      positioning under the joint depression site. Reduction was achieved by expanding
      the balloon and stabilisation by injecting the cavity with resorbable tricalcium
      phosphate cement in the younger patients and polymethyl-metacrylate cement in the
      two elderly patients with osteoporosis. No internal fixation was used. RESULTS:
      No intra-operative, postoperative, or delayed complications were recorded. Median
      hospital stay length was 4.5 days (range, 3-7 days). All the fractures healed
      within the usual timeframe, without loss of reduction. Median time to full weight
      bearing ambulation was 52.5 days (range, 15-75 days). The functional outcomes
      correlated with the good anatomic results, with a median American Orthopaedic
      Foot and Ankle Society score of 87.0 (range, 86-97). DISCUSSION: This preliminary
      study shows that balloon reduction and cement fixation of intra-articular
      calcaneal fractures is easy to perform, reproducible, and devoid of specific
      complications. Good-quality reduction and stabilisation until fracture healing
      were achieved, and time to recovery of self-sufficiency was short, even in
      elderly patients with osteoporosis. These results support the use of this
      minimally invasive technique. LEVEL OF EVIDENCE: Level IV, retrospective study.

PMID- 24095599
TI  - Factors affecting accurate drill sleeve insertion in locking compression plates.
AB  - BACKGROUND: Accurate positioning of locking screws depends on accurate insertion
      of the drill sleeve into the locking compression plate (LCP). The purpose of the
      present study was to determine factors affecting accurate drill sleeve insertion.
      HYPOTHESIS: Tilting and shallow locking screw holes and combination-type holes
      make it difficult to insert the drill sleeve in the LCP. MATERIALS AND METHODS:
      Twenty-seven 3.5mm LCP metaphyseal insertion holes were selected (Philos((r)),
      LPHP((r)), DMTP((r)), low-band DMTP((r)) [Synthes, Solothurn, Switzerland]). Two
      orthopedic surgeons checked the time taken for accurate insertion of the drill
      sleeve into the plate. Variables relating to LCP drill sleeve insertion time were
      analyzed. RESULTS: It took an average 6.6seconds to insert the drill sleeve
      accurately in the holes. Insertion time increased with the tilt of the screw hole
      but not with shallowness. Insertion time in combination-type holes was longer
      (8.8seconds) than in single locking holes (5.6seconds). DISCUSSION: Tilted screw
      holes and combination-type holes affect the insertion of the drill sleeve into
      3.5mm LCPs. LEVEL OF EVIDENCE: Level IV, experimental study.

PMID- 24095600
TI  - The establishment and validation of efficient assays for anti-IIa and anti-Xa
      activities of heparin sodium and heparin calcium.
AB  - Heparin is used as an anticoagulant drug. The anticoagulation process is mainly
      caused by the interaction of heparin with antithrombin followed by inhibition of
      anticoagulant factor IIa and factor Xa. The anti-factor IIa and anti-factor Xa
      activities of heparin are critical for its anticoagulant effect; however,
      physicochemical methods that can reflect these activities have not been
      established. Thus, the measurements of anti-IIa and anti-Xa activities by
      biological assay are critical for the quality control of heparin products.
      Currently in the Japanese Pharmacopoeia (JP), the activities of heparin sodium
      and heparin calcium are measured by an anti-Xa activity assay (anti-Xa assay),
      but anti-IIa activity is not measured. Here, we established an anti-IIa activity
      assay (anti-IIa assay) and an anti-Xa assay having good accuracy and precision.
      When samples having a relative activity of 0.8, 1.0 and 1.2 were measured by the
      established anti-IIa and anti-Xa assays in nine laboratories, good accuracy
      (100.0-102.8% and 101.6-102.8%, respectively), good intermediate precision (1.9
      2.1% and 2.4-4.2%, respectively) and good reproducibility (4.0-4.8% and 3.6-6.4%,
      respectively) were obtained. The established anti-IIa and anti-Xa assays have
      similar protocols, and could be performed by a single person without a special
      machine. The established assays would be useful for quality control of heparin. 

PMID- 24095601
TI  - Satiety and the role of MU-opioid receptors in the portal vein.
AB  - Mu-opioid receptors (MORs) are known to influence food intake at the brain level,
      through their involvement in the food reward system. MOR agonists stimulate food
      intake. On the other hand, MOR antagonists suppress food intake. MORs are also
      active in peripheral organs, especially in the small intestine where they control
      the gut motility. Recently, an indirect role in the control of food intake was
      ascribed to MORs in the extrinsic gastrointestinal neural system. MORs present in
      the neurons of the portal vein walls sense blood peptides released from the
      digestion of dietary protein. These peptides behave as MOR antagonists. Their MOR
      antagonist action initiates a gut-brain circuitry resulting in the induction of
      intestinal gluconeogenesis, a function controlling food intake. Thus, periportal
      MORs are a key mechanistic link in the satiety effect of protein-enriched diets. 

PMID- 24095602
TI  - Incretin actions beyond the pancreas: lessons from knockout mice.
AB  - Glucose-dependent insulinotropic polypeptide (GIP) and glucagon-like peptide-1
      (GLP-1) are intestinal hormones secreted in response to ingestion of various
      nutrients. These incretins stimulate insulin secretion from pancreatic beta cells
      in a glucose-dependent fashion. GIP and GLP-1 actions are mediated by specific
      receptors, the GIP receptor (GIPR) and the GLP-1 receptor (GLP-1R), which are
      expressed in pancreatic beta cells and various other tissues and organs.
      Investigations using mice deficient in GIPR and/or GLP-1R have clarified roles of
      the incretins in enhancement of glucose-dependent insulin secretion from
      betacells as well as divergent biological activities with therapeutic
      implications for diabetes-related complications, such as cardiovascular diseases,
      retinopathy, nephropathy and neuropathy, and comorbidities, such as cognitive
      impairment, bone fracture and obesity. We review here recent findings on the
      extra-pancreatic effects of GIP and GLP-1 from the perspective of diabetes
      treatment. 

PMID- 24095603
TI  - The vestibulocochlear nerve (VIII).
AB  - The vestibulocochlear nerve (8th cranial nerve) is a sensory nerve. It is made up
      of two nerves, the cochlear, which transmits sound and the vestibular which
      controls balance. It is an intracranial nerve which runs from the sensory
      receptors in the internal ear to the brain stem nuclei and finally to the
      auditory areas: the post-central gyrus and superior temporal auditory cortex. The
      most common lesions responsible for damage to VIII are vestibular Schwannomas.
      This report reviews the anatomy and various investigations of the nerve. 

PMID- 24095604
TI  - [Effectiveness of a nursing intervention on patient anxiety before transfusion of
      packed red blood cells].
AB  - OBJECTIVES: To evaluate the effectiveness of an educational intervention
      regarding anxiety and satisfaction in patients requiring a red blood cell
      transfusion. METHOD: Randomised, controlled, single-blind clinical trial in
      patients requiring a packed red blood cell transfusion. SAMPLE SIZE: alpha=.05,
      beta=.10, to detect a 10% difference, 70 subjects in each group. The sampling
      recruitment was randomised to the intervention group (IG) and the control group
      (CG). INDEPENDENT VARIABLES: an intervention protocol with oral and written
      information using a published guide on the safety, risks and benefits of
      haemotherapy for the IG, and an equivalent one on general health topics for the
      CG. DEPENDENT VARIABLES: pre- and post-anxiety state; Spielberger's validated
      questionnaire: STAI. Satisfaction, by an ad hoc questionnaire. Sociodemographic
      and clinical variables: description, reason for transfusion, prescription
      knowledge, incidents, records. RESULTS: There was a total of 144 subjects, 73
      (50.69%) in the IG, and 71 (49.31%) in the CG. The mean age was 55.80 years, with
      56.94% males, and a first transfusion in 52.08%. Comparability between the IG and
      the CG was tested and confirmed. The decrease in anxiety after the intervention
      for the IG was 19.99, compared to 25.48 in CG. The difference was greater than
      the proposed 10%, and was statistically significant. The preference for
      information was 98.60% in IG, compared to 43.70% in CG. CONCLUSIONS: The
      hypothesis was confirmed; a protocolised nursing educational intervention
      protocol increased patient satisfaction with nursing care, and decreased patient
      anxiety, thus preventing complications and providing greater safety to the users.

PMID- 24095605
TI  - Focal choroidal excavation complicated by choroidal neovascularization.
AB  - PURPOSE: To evaluate the clinical findings of focal choroidal excavation (FCE)
      complicated by choroidal neovascularization (CNV). DESIGN: Retrospective,
      observational case series. PARTICIPANTS: Twelve patients (15 eyes) with FCE and
      CNV. METHODS: The medical records of the patients were reviewed. Clinical
      findings including age, sex, refraction, color photography, fundus fluorescein
      angiography (FFA), indocyanine green angiography (ICGA), and spectral-domain
      optical coherence tomography (OCT) were analyzed. MAIN OUTCOME MEASURES: Fundus
      fluorescein angiography, ICGA, and OCT findings. RESULTS: The 12 patients
      included 6 women and 6 men. The mean age was 46.8+/-13.4 years (range, 26-64
      years). One half of the patients were emmetropic, and the others were myopic (
      0.5 to -3.0 diopters). All subjects were Chinese. Before CNV development, normal
      appearance or nonspecific pigment disturbance could be seen around the choroidal
      excavation. Corresponding to the excavation, window defects were observed by FFA,
      whereas hypofluorescence was found on ICGA images. Choroidal neovascularization
      in all eyes was classic as revealed by FFA. The OCT images showed that all eyes
      had a single choroidal excavation. In 7 of the 15 eyes, the choroidal excavation
      was located subfoveally, and in the other 8 eyes, it was eccentric. All CNV
      lesions grew from the bottom or slope of the excavation. Three patients had
      bilateral involvement. Choroidal neovascularization occurred in both conforming
      and nonconforming type FCEs, regardless of whether the excavation was shallow or
      deep, subfoveal or eccentric. All CNV lesions responded well to intravitreal
      injection of anti-vascular endothelial growth factor (VEGF) agents. After a
      single injection, CNV regressed in 13 of 15 eyes. Two eyes received an additional
      injection. Nonconforming FCE changed to the conforming type after successful
      treatment of CNV. CONCLUSIONS: Focal choroidal excavation is not always stable.
      Choroidal neovascularization commonly can be seen in patients with FCE and
      responds well to intravitreal anti-VEGF agents.

PMID- 24095606
TI  - Comparison of direct and indirect bronchoprovocation testing using ventilator
      acquired pulmonary mechanics in healthy cats and cats with experimental allergic
      asthma.
AB  - Airway hyperresponsiveness (AHR) is a key feature of asthma and can be measured
      using bronchoprovocation. Direct (methacholine, MCh) or indirect (adenosine-5
      monophosphate, AMP; or mannitol) bronchoprovocants are used in human patients,
      the latter inducing AHR only with pre-existing airway inflammation. The present
      study compared the responses to direct (MCh) and indirect (mannitol, AMP)
      bronchoprovocation in healthy and asthmatic cats (n=6/group). The order of
      bronchoprovocant was randomized using a published table of random numbers and
      there was a 1-month washout before crossover to the next treatment. Pulmonary
      mechanics were measured in anesthetized and mechanically ventilated cats using a
      critical care ventilator. Saline at baseline and increasing doses of each
      bronchoprovocant were aerosolized for 30 s, followed by 4 min of data collection
      between doses. The endpoint for each bronchoprovocant was reached when airway
      resistance exceeded 200% of baseline values (EC200Raw). There was a significant
      difference (P<0.001) in the airway response of asthmatic vs. healthy cats over
      the range of MCh concentrations, despite there being no significant difference in
      the EC200Raw between the groups. Response to MCh was significantly greater
      (P<0.05) in asthmatic than in healthy cats at MCh concentrations as low as 0.0625
      mg/mL. For AMP, a small subset of asthmatics (n=2/6) responded at low
      concentrations; four asthmatic cats and all healthy cats failed to respond even
      to the highest concentrations of AMP. One asthmatic cat but no healthy cats
      responded to mannitol. In conclusion, MCh discriminated asthmatic from healthy
      cats but neither AMP nor mannitol was an effective bronchoprovocant in this
      model.

PMID- 24095607
TI  - Contrast echocardiography to assess left ventricular volume and function in
      Beagle dogs: comparison with 3-Tesla dual source parallel cardiac magnetic
      resonance imaging.
AB  - This study was performed to evaluate the effect and feasibility of contrast
      echocardiography (CE) compared with unenhanced echocardiography (UE) and cardiac
      magnetic resonance imaging (CMRI) to assess left ventricular (LV) volume and
      function, including end-diastolic volume (EDV), end-systolic volume (ESV), stroke
      volume (SV), and ejection fraction (EF) in six healthy Beagles. When the dogs
      were conscious, LV measurements using CE were significantly higher than those
      obtained using UE, except for EF, and were similar to the values obtained using
      CMRI. Additionally, EDV, SV, and EF obtained using UE from anesthetized dogs were
      significantly lower than those obtained using CE or CMRI. Measurements of EDV, SV
      and EF using CE were not significantly different from the corresponding
      measurements obtained using CMRI (31.13+/-2.18 vs. 32.88+/-1.17 mL, 18.41+/-1.25
      vs. 17.92+/-0.96 mL, 59.29+/-2.29% vs. 53.33+/-1.69%, respectively). Inter
      observer agreements for UE (0.74+/-0.05) were lower than those for CE (0.80+/
      0.04) and CMRI (0.92+/-0.03). In conclusion, LV function was assessed
      reproducibly using CE, and the measurements obtained were consistent with
      reference standard measurements obtained using CMRI. Measurements made using CE
      agreed more closely with CMRI than those made using UE.

PMID- 24095608
TI  - Mycobacterium bovis infection in domestic pigs in Great Britain.
AB  - Mycobacterium bovis, the causative agent of bovine tuberculosis (TB), infects a
      wide range of wild and domestic mammals. Despite a control programme spanning
      decades, M. bovis infection levels in cattle in Great Britain (GB) have continued
      to rise over recent years. As the incidence of infection in cattle and wildlife
      may be linked to that in swine, data relating to infection of pigs identified at
      slaughter were examined in this study. Between 2007 and 2011, almost all M. bovis
      infected pigs originated from farms in the South-West and West-Midland regions of
      England. The data suggest that pigs raised outdoors or on holdings with poor
      biosecurity may be more vulnerable to infection with M. bovis. In the majority of
      cases, the same strains of M. bovis were found in pigs and cattle, despite that
      fact that direct contact between these species was rarely observed. Genotyping
      and geographical mapping data indicated that some strains found in pigs may
      correlate better with those present in badgers, rather than cattle. In
      consequence, it is proposed that pigs may represent a useful sentinel for M.
      bovis infection in wildlife in GB. Given the potential implications of this
      infection for the pig industry, and for the on-going effort to control bovine TB,
      the importance of understanding the epidemiology and pathogenesis of M. bovis
      infection, as well as monitoring its prevalence, in pigs should not be
      underestimated. 

PMID- 24095609
TI  - Adjuvant treatment of premenopausal women with endocrine-responsive early breast
      cancer: design of the TEXT and SOFT trials.
AB  - OBJECTIVES: In 2003 the International Breast Cancer Study Group (IBCSG) initiated
      the TEXT and SOFT randomized phase III trials to answer two questions concerning
      adjuvant treatment for premenopausal women with endocrine-responsive early breast
      cancer: 1-What is the role of aromatase inhibitors (AI) for women treated with
      ovarian function suppression (OFS)? 2-What is the role of OFS for women who
      remain premenopausal and are treated with tamoxifen? METHODS: TEXT randomized
      patients to receive exemestane or tamoxifen with OFS. SOFT randomized patients to
      receive exemestane with OFS, tamoxifen with OFS, or tamoxifen alone. Treatment
      was for 5 years from randomization. RESULTS: TEXT and SOFT successfully met their
      enrollment goals in 2011. The 5738 enrolled women had lower-risk disease and
      lower observed disease-free survival (DFS) event rates than anticipated.
      Consequently, 7 and 13 additional years of follow-up for TEXT and SOFT,
      respectively, were required to reach the targeted DFS events (median follow-up
      about 10.5 and 15 years). To provide timely answers, protocol amendments in 2011
      specified analyses based on chronological time and median follow-up. To assess
      the AI question, exemestane + OFS versus tamoxifen + OFS, a combined analysis of
      TEXT and SOFT became the primary analysis (n = 4717). The OFS question became the
      primary analysis from SOFT, assessing the unique comparison of tamoxifen + OFS
      versus tamoxifen alone (n = 2045). The first reports are anticipated in mid- and
      late-2014. CONCLUSIONS: We present the original designs of TEXT and SOFT and
      adaptations to ensure timely answers to two questions concerning optimal adjuvant
      endocrine treatment for premenopausal women with endocrine-responsive breast
      cancer. Trial Registration TEXT: Clinicaltrials.govNCT00066703 SOFT:
      Clinicaltrials.govNCT00066690.

PMID- 24095610
TI  - Challenging single- and multi-probesets gene expression signatures of
      pathological complete response to neoadjuvant chemotherapy in breast cancer:
      experience of the REMAGUS 02 phase II trial.
AB  - This study was designed to identify predictive signatures of pathological
      complete response (pCR) in breast cancer treated by taxane-based regimen, using
      clinicopathological variables and transcriptomic data (Affymetrix Hgu133 Plus 2.0
      devices). The REMAGUS 02 trial (n = 153,training set) and the publicly available
      M.D. Anderson data set (n = 133, validation set) were used. A re-sampling method
      was applied. All predictive models were defined using logistic regression and
      their classification performances were tested through Area Under the Curve (AUC)
      estimation. A stable set of 42 probesets (31 genes) differentiate pCR or no pCR
      samples. Single-or 2-probesets signatures, mainly related to ER pathway, were
      equally predictive of pCR with AUC greater then 0.80. Models including probesets
      associated with ESR1, MAPT, CA12 or PIGH presented good classification
      performances. When clinical variables were entered into the model, only CA12 and
      PIGH, remained informative (p = 0.05 and p = 0.005) showing that a combination of
      a few genes provided robust and reliable prediction of pCR. 

PMID- 24095611
TI  - Axillary ultrasound for preoperative nodal staging in breast cancer patients: is
      it of added value?
AB  - BACKGROUND: New insights show that an axillary lymph node dissection (ALND) may
      not always be indicated for metastases detected by ultrasound (pathologically
      proven). This study investigated whether axillary ultrasound accurately predicts
      pN0, pN1 and pN2-pN3 status. METHODS: Data were retrospectively collected from
      all consecutive patients with invasive breast cancer who underwent (primary)
      surgery between 2008 and 2012. False negative percentages and negative predictive
      values (NPVs) for sonographic nodal staging were calculated for all patients and
      again for cT1-2 patients treated by breast conserving therapy (BCT). RESULTS: A
      total of 577 axillary ultrasounds were included. After negative ultrasound
      findings (cN0), pathology showed pN2-pN3 disease in 4.4% of these cases, with an
      NPV of 95.5% (93.4-97.1%). When cN1 (1-3 suspicious nodes) was predicted,
      pathology showed pN2-pN3 disease in 41.2%, with an NPV of 58.5% (44.2-71.5%). In
      the subgroup of patients with cT1-2 breast cancer that were treated by BCT,
      pathology showed pN2-pN3 disease in 2.3% after negative ultrasound findings
      (cN0), with an NPV of 97.7% (94.9-99.0%). When cN1 was predicted (n = 12),
      pathology showed pN2-pN3 disease in 50.0%, with an NPV of 50.0% (22.3-77.9%). A
      direct ALND was performed in these 12 cN1 cases; pathology showed six patients
      with pN1 (three patients with one and three with two macrometastases) and six
      with pN2-pN3 disease (4, 5, 11, 13, 16 or 22 macrometastases, respectively).
      CONCLUSION: In conclusion, a negative axillary ultrasound generally excludes the
      presence of pN2-pN3 disease. An axillary ultrasound cannot accurately
      differentiate between pN1 and pN2-pN3. It could be argued that the standard
      performance of an axillary ultrasound in breast cancer patients is questionable;
      multidisciplinary discussion could guide decisions on the use of axillary
      ultrasound for the individual patient.

PMID- 24095612
TI  - Experimental investigation and modeling of dissolved organic carbon removal by
      coagulation from seawater.
AB  - Coagulation removes colloidal matters and dissolved organic carbon (DOC) which
      can cause irreversible membrane fouling. However, how DOC is removed by coagulant
      is not well-known. Jar test was used to study the removal of hydrophobic and
      hydrophilic DOC fractions at various doses (0.5-8.0 mg-Fe(+3) L(-1)) of ferric
      chloride (FeCl3) and pH (5.0-9.0). Natural organic matter (NOM) in seawater and
      treated seawater were fractionated by liquid chromatography-organic carbon
      detector (LC-OCD). Compared to surface water, the removal of DOC in seawater by
      coagulation was remarkably different. Majority of DOC could be easily removed
      with very low coagulant dose (<5.0 mg-Fe(+3) L(-1)) and the removal efficiency
      did not vary with pH, but the DOC composition in treated water had significantly
      changed. Hydrophobic fraction (HB) was better removed at high pH while
      hydrophilic fraction (HF) was better removed at low pH. A modified model of Kastl
      et al. (2004) which assumed that the removal occurred by adsorption of un
      dissociated compounds onto ferric hydroxide was formulated and successfully
      validated against the jar test data.

PMID- 24095613
TI  - In vivo genotoxicity assessment of titanium, zirconium and aluminium
      nanoparticles, and their microparticulated forms, in Drosophila.
AB  - As in vivo system, we propose Drosophila melanogaster as a useful model for study
      the genotoxic risks associated with nanoparticle exposure. In this study we have
      carried out a genotoxic evaluation of titanium dioxide (TiO2), zirconium oxide
      (ZrO2) and aluminium oxide (Al2O3) nanoparticles and their microparticulated
      forms in D. melanogaster by using the wing somatic mutation and recombination
      assay. This assay is based on the principle that loss of heterozygosis and the
      corresponding expression of the suitable recessive markers, multiple wing hairs
      and flare-3, can lead to the formation of mutant clones in treated larvae, which
      are expressed as mutant spots on the wings of adult flies. Third instar larvae
      were feed with TiO2, ZrO2 and Al2O3 nanoparticles, and their microparticulated
      forms, at concentrations ranging from 0.1 to 10mM. Although a certain level of
      aggregation/agglomeration was observed in solution, it must be noted than the
      constant digging activity of larvae ensures that treated medium pass constantly
      through the digestive tract ensuring exposure. The results showed that no
      significant increases in the frequency of all spots (e.g. small single, large
      single, twin, total mwh and total spots) were observed, indicating that these
      nanoparticles were not able to induce genotoxic activity in the wing spot assay
      of D. melanogaster. Negative data were also obtained with the microparticulated
      forms. This indicates that the nanoparticulated form of the selected
      nanomaterials does not modify the potential genotoxicity of their
      microparticulated versions. These in vivo results contribute to increase the
      genotoxicity database on the TiO2, ZrO2 and Al2O3 nanoparticles.

PMID- 24095614
TI  - Effects of chain length and pH on the uptake and distribution of perfluoroalkyl
      substances in maize (Zea mays).
AB  - Maize is the most important grain crop grown for human nutrition, animal fodder
      and biogas production worldwide. Nonetheless, no systematic studies have been
      undertaken on these plants to examine the uptake mechanisms for perfluoroalkyl
      substances (PFASs) dependent upon chain length and pH value. The aim of the
      present study was therefore to determine the influence of chain length (C4 to
      C10) and pH value (pH 5, pH 6, pH 7) on the uptake and distribution of seven
      perfluoroalkyl carboxylic acids (PFCAs) and three perfluoroalkane sulfonic acids
      (PFSAs) by maize in nutrient solution experiments under controlled conditions in
      a climate chamber. A pH-dependent uptake was observed for perfluorodecanoic acid
      (PFDA) with an uptake rate of 2.51 MUg g(-1) at pH 5 compared to 1.52 MUg g(-1)
      root dry weight (DW) per day (d) at pH 7. Perfluorobutanoic acid (PFBA) had the
      highest uptake rate within the group of PFCAs with an average of 2.46 MUg g(-1)
      root DWd(-1) and perfluorooctane sulfonic acid (PFOS) had the highest uptake rate
      (3.63 MUg g(-1) root DWd(-1)) within the group of PFSAs. The shoot:root ratio for
      shorter-chain PFCAs (<= C7) and PFBS (C4) was >2.0, which indicates that shorter
      chain PFASs are transferred predominantly and at higher concentrations to the
      shoot. In contrast, long-chain PFCAs such as perfluorooctanoic acid (PFOA),
      perfluorononanoic acid (PFNA) and perfluorodecanoic acid (PFDA) as well as the
      PFASs perfluorohexane sulfonic acid (PFHxS) and perfluorooctane sulfonic acid
      (PFOS) accumulated at higher concentrations in the roots of maize plants with a
      shoot:root ratio of <1.0.

PMID- 24095615
TI  - Stability of solid-phase selenium species in fly ash after prolonged submersion
      in a natural river system.
AB  - Selenium (Se) chemistry can be very complex in the natural environment,
      exhibiting different valence states (-2, 0, +4, +6) representing multiple
      inorganic, methylated, or complexed forms. Since redox associated shifts among
      most of known Se species can occur at environmentally relevant conditions, it is
      important to identify these species in order to assess their potential toxicity
      to organisms. In June of 2009, researchers from the US Army Engineer Research &
      Development Center (ERDC) conducted investigations of the fly ash spilled 6
      months previously into the Emory River at the TVA Kingston Fossil Plant, TN. Ash
      samples were collected on site from both the original ash pile (that did not move
      during the levee failure), from the spill zone (including the Emory River), and
      from the ash recovery ditch (ARD) containing ash removed during dredging cleanup
      operations. The purpose of this work was to determine the state of Se in the
      spilled fly ash and to assess its potential for transformation and resultant
      chemical stability from its prolonged submersion in the river and subsequent
      dredging. Sequential chemical extractions suggested that the river environment
      shifted Se distribution toward organic/sulfide species. Speciation studies by
      bulk XANES analysis on fly ash samples showed that a substantial portion of the
      Se in the original ash pile had transformed from inorganic selenite to a mixture
      of Se sulfide and reduced (organo)selenium (Se(-II)) species over the 6-month
      period. MU-XRF mapping data showed that significant trends in the co-location of
      Se domains with sulfur and ash heavy metals. Ten-d extended elutriate tests
      (EETs) that were bubbled continuously with atmospheric air to simulate worst-case
      oxidizing conditions during dredging showed no discernible change in the
      speciation of fly ash selenium. The enhanced stability of the organo- and sulfide
      selenium species coincided with the mixture of the ash material with humic
      materials in the river, corresponding with notable shifts in the ash carbon- and
      nitrogen-functionality.

PMID- 24095616
TI  - The effects of intra-arterial vasodilators on radial artery size and spasm:
      implications for contemporary use of trans-radial access for coronary angiography
      and percutaneous coronary intervention.
AB  - BACKGROUND: Transradial access (TRA) offers advantages including decreased
      vascular complications, reduced length of hospital stay, and reduced cost. The
      size of the radial artery (RA) limits the equipment that can be used via TRA.
      Intra-arterial (IA) vasodilators prevent and treat RA spasm, yet are not
      uniformly used in TRA and their effect on the absolute size of the RA remains
      unknown. METHODS AND MATERIALS: 121 patients undergoing TRA for cardiac
      catheterization were included. 78 patients underwent RA angiography prior to
      administration of IA vasodilators ('no vasodilator' group), 43 patients underwent
      radial angiography after administration of an IA verapamil and nitroglycerin
      cocktail ('vasodilator' group). Quantitative angiography was used to compare the
      RA diameters. RESULTS: Clinical characteristics were similar between the groups,
      except that patients in the 'no vasodilator' cohort were taller (1.67 +/- 0.1 m
      vs. 1.73 +/- 0.1 m, p=0.002), and heavier (84.9 +/- 18.2 kg vs. 75 +/- 17.1 kg,
      p=0.003). In the 'vasodilator' group the proximal RA diameter was larger (2.29 +/
      0.47 mm vs. 2.09 +/- 0.41 mm, p=0.02) as was the narrowest segment (1.83 +/-
      0.56 mm vs 1.39 +/- 0.43, p<0.0001) compared to the 'no vasodilator' group. At
      the RA origin, 79.4% of those in the 'vasodilator' group were larger than a 6 Fr
      guide catheter, compared to 51.4% in the 'no vasodilator' group (p=0.004). At the
      narrowest segment a higher percentage of RAs in the 'vasodilator' group were
      larger than a 5 Fr guide catheter (65.1% vs 26.9%, p<0.001) and a 6 Fr catheter
      (34.9% vs 10.3%, p=0.001). CONCLUSION: IA vasodilators increase pre-procedural RA
      diameter in patients undergoing cardiac catheterization via TRA. This increase in
      diameter has important implications for procedural planning. SUMMARY FOR TABLE OF
      CONTENTS: Boyer et al. performed a blinded controlled clinical trial
      investigating the effects of intra-arterial vasodilators on radial artery size
      and spasm during cardiac catheterization. The study demonstrates that intra
      arterial vasodilators significantly increased the radial artery size throughout
      the entire course of the vessel and significantly decreased the amount of radial
      artery spasm. The authors conclude that these findings support the use of intra
      arterial vasodilators during cardiac catheterization and have important
      implications for emerging technologies such as larger bore sheathless radial
      procedures.

PMID- 24095617
TI  - Relation between brain architecture and mathematical ability in children: a DBM
      study.
AB  - Population-based studies indicate that between 5 and 9 percent of US children
      exhibit significant deficits in mathematical reasoning, yet little is understood
      about the brain morphological features related to mathematical performances. In
      this work, deformation-based morphometry (DBM) analyses have been performed on
      magnetic resonance images of the brains of 79 third graders to investigate
      whether there is a correlation between brain morphological features and
      mathematical proficiency. Group comparison was also performed between Math
      Difficulties (MD-worst math performers) and Normal Controls (NC), where each
      subgroup consists of 20 age and gender matched subjects. DBM analysis is based on
      the analysis of the deformation fields generated by non-rigid registration
      algorithms, which warp the individual volumes to a common space. To evaluate the
      effect of registration algorithms on DBM results, five nonrigid registration
      algorithms have been used: (1) the Adaptive Bases Algorithm (ABA); (2) the Image
      Registration Toolkit (IRTK); (3) the FSL Nonlinear Image Registration Tool; (4)
      the Automatic Registration Tool (ART); and (5) the normalization algorithm
      available in SPM8. The deformation field magnitude (DFM) was used to measure the
      displacement at each voxel, and the Jacobian determinant (JAC) was used to
      quantify local volumetric changes. Results show there are no statistically
      significant volumetric differences between the NC and the MD groups using JAC.
      However, DBM analysis using DFM found statistically significant anatomical
      variations between the two groups around the left occipital-temporal cortex, left
      orbital-frontal cortex, and right insular cortex. Regions of agreement between at
      least two algorithms based on voxel-wise analysis were used to define Regions of
      Interest (ROIs) to perform an ROI-based correlation analysis on all 79 volumes.
      Correlations between average DFM values and standard mathematical scores over
      these regions were found to be significant. We also found that the choice of
      registration algorithm has an impact on DBM-based results, so we recommend using
      more than one algorithm when conducting DBM studies. To the best of our
      knowledge, this is the first study that uses DBM to investigate brain anatomical
      features related to mathematical performance in a relatively large population of
      children. 

PMID- 24095618
TI  - Pilot trial: pregabalin on colonic sensorimotor functions in irritable bowel
      syndrome.
AB  - BACKGROUND: In prior studies, pregabalin reduced rectal or colonic pain in
      patients with irritable bowel syndrome and healthy adults, suggesting reduction
      of afferent function. AIM: To assess effects of pregabalin on colonic compliance,
      sensory and motor functions in patients with constipation-predominant irritable
      bowel syndrome. METHODS: In a pilot, double-blind, placebo-controlled, parallel
      group study, we tested oral pregabalin, 200mg, in 18 patients with constipation
      predominant irritable bowel syndrome. With a barostatically controlled
      polyethylene balloon in the left colon, we assessed sensation thresholds and
      colonic compliance using ascending method of limits, sensation ratings over 4
      levels of distension, fasting and postprandial colonic tone and phasic motility.
      Analysis of covariance (adjusted for the corresponding pre-drug response) was
      used to compare placebo and pregabalin. After 45% participants completed studies,
      we conducted an interim analysis to assess the conditional power to detect pre
      specified treatment effects given the observed variation and treatment group
      differences based on the planned sample size for the trial. RESULTS: Pregabalin
      did not significantly affect colonic compliance, sensation thresholds, sensation
      ratings, fasting or postprandial tone or motility index. The study was stopped
      for futility to detect an effect on visceral pain with the planned design and
      sample size. CONCLUSION: Pregabalin, 200mg, might not reduce distension-related
      colonic pain in constipation-predominant irritable bowel syndrome patients.

PMID- 24095619
TI  - Performance of AnyplexTM II multiplex real-time PCR for the diagnosis of seven
      sexually transmitted infections: comparison with currently available methods.
AB  - OBJECTIVES: The real-time PCR assay is the most sensitive test for screening and
      diagnosing sexually transmitted infections (STIs) and has made diagnosing these
      infections easier for clinicians. The aim of this study was to investigate the
      reliability, accuracy, and usefulness of the real-time multiplex PCR assay for
      the detection of seven sexually transmitted microorganisms in clinical samples.
      METHODS: A total of 897 specimens from 365 symptomatic patients and 532
      asymptomatic volunteers were collected over a 10-month period. A total of 696
      subjects provided 50ml of first-voided urine as samples, and 201 female patients
      provided endocervical swab specimens. Chlamydia trachomatis, Neisseria
      gonorrhoeae, Trichomonas vaginalis, Mycoplasma genitalium, Mycoplasma hominis,
      Ureaplasma urealyticum, and Ureaplasma parvum were tested for using five
      diagnostic methods: multiplex real-time PCR (AnyplexTM II), multiplex PCR
      (Seeplex(r)), strand displacement amplification (SDA, BD ProbeTecTM ET), PCR
      (AmpliSens(r)), and a commercially available Mycoplasma IST 2 Kit. RESULTS:
      Multiplex real-time PCR (AnyplexTM II) showed outstanding results in all fields,
      particularly sensitivity and specificity, compared with other diagnostic tools.
      This method yielded 100% sensitivity and high specificity for the detection of C.
      trachomatis, N. gonorrhoeae, T. vaginalis, M. genitalium, and M. hominis. It was
      also useful for discriminating between U. urealyticum and U. parvum. CONCLUSIONS:
      Multiplex real-time PCR was found to be an equivalent or superior modality for
      the diagnosis of STIs. It could be a cost-effective and rapid diagnostic tool for
      the simultaneous detection of multiple STI microorganisms.

PMID- 24095620
TI  - Vegetable variety is a key to improved diet quality in low-income women in
      California.
AB  - Primary prevention education interventions, including those sponsored by the US
      Department of Agriculture for low-income families, encourage and support
      increases in vegetable intake. Promoting vegetable variety as a focal point for
      behavior change may be a useful strategy to increase vegetable consumption. A
      simple vegetable variety evaluation tool might be useful to replace the time
      intensive 24-hour dietary recall. The purpose of our study was to determine
      whether vegetable variety is associated with vegetable consumption and diet
      quality among US Department of Agriculture program participants. Variety of
      vegetable intake and measures of total vegetable intake, diet quality, and diet
      cost were evaluated. Low-income, female participants (N=112) aged 20 to 55 years
      with body mass index 17.7 to 68.5 who were the primary food purchasers/preparers
      for their households were recruited from four California counties representing
      rural, urban, and suburban areas. Energy density and Healthy Eating Index-2005
      were used to assess diet quality. Vegetable variety was based on number of
      different vegetables consumed per week using a food frequency questionnaire, and
      three groups were identified as: low variety, <=5 different vegetables per week;
      moderate variety, 6 to 9 vegetables per week; and high variety, >=10 vegetables
      per week. Compared with the low-variety group, participants in the high-variety
      group ate a greater quantity of vegetables per day (P<0.001); their diets had a
      higher Healthy Eating Index score (P<0.001) and lower energy density (P<0.001);
      and costs of their daily diet and vegetable use were higher (P<0.001). Thus,
      greater vegetable variety was related to better overall diet quality, a larger
      quantity of vegetables consumed, and increased diet cost. 

PMID- 24095621
TI  - Dietary patterns and total mortality in a Mediterranean cohort: the SUN project.
AB  - BACKGROUND: Different dietary patterns have been associated with several health
      outcomes, including morbidity and mortality. There is little evidence on the
      association between empirically derived dietary patterns and all-cause mortality
      in Southern European populations. OBJECTIVE: The aim of our study was to
      prospectively evaluate the association between an empirically derived dietary
      pattern and all-cause mortality. DESIGN: The Seguimiento Universidad de Navarra
      (SUN) Project is an ongoing, multipurpose, prospective and dynamic Spanish
      cohort. PARTICIPANTS/SETTING: Participants were a prospective cohort of 16,008
      middle-aged Spanish adults. All of them were university graduates (alumni) (59.6%
      women, mean age 38 years). Usual diet was assessed at baseline with a validated
      semiquantitative food frequency questionnaire. MAIN OUTCOME MEASURES: Deaths were
      confirmed by review of medical records and of the National Death Index.
      STATISTICAL ANALYSIS: Dietary patterns were ascertained through a factor
      (principal component) analysis based on 30 predefined food groups. Participants
      were classified according to tertiles of adherence to the three main dietary
      patterns identified with factor analysis. Cox regression models were fitted to
      estimate multivariable-adjusted hazard ratios and 95% CIs for mortality. RESULTS:
      Three major dietary patterns were identified. They were labelled Western dietary
      pattern (rich in red and processed meat, potatoes, and fast food), Mediterranean
      dietary pattern (rich in vegetables, fish and seafood, fruits, and olive oil),
      and alcoholic beverages dietary pattern. During follow-up, 148 deaths were
      reported (mean age at death 54.5 years). After adjustment for potential
      confounders, the lowest risk of all-cause mortality was found in the tertile of
      highest adherence to the Mediterranean dietary pattern (adjusted hazard ratio for
      third vs first tertile 0.53, 95% CI 0.34 to 0.84) (P for trend <0.01). The
      Western dietary pattern and alcoholic beverages dietary pattern showed no
      significant association with mortality. CONCLUSIONS: Greater adherence to an
      empirically derived dietary pattern approaching the traditional Mediterranean
      diet was associated with a reduction in the risk of all-cause mortality among
      middle-aged Mediterranean adults.

PMID- 24095622
TI  - Changes in the energy and sodium content of main entrees in US chain restaurants
      from 2010 to 2011.
AB  - BACKGROUND: The food environment shapes individual diets, and as food options
      change, energy and sodium intake may also shift. Understanding whether and how
      restaurant menus evolve in response to labeling laws and public health pressures
      could inform future efforts to improve the food environment. OBJECTIVES: To track
      changes in the energy and sodium content of US chain restaurant main entrees
      between spring 2010 (when the Affordable Care Act was passed, which included a
      federal menu labeling requirement) and spring 2011. DESIGN: Nutrition information
      was collected from top US chain restaurants' websites, comprising 213 unique
      brands. Descriptive statistics and regression analysis evaluated change across
      main entrees overall and compared entrees that were added, removed, and
      unchanged. Tests of means and proportions were conducted for individual
      restaurant brands to see how many made significant changes. Separate analyses
      were conducted for children's menus. RESULTS: Mean energy and sodium did not
      change significantly overall, although mean sodium was 70 mg lower across all
      restaurants in added vs removed menu items at the 75th percentile. Changes were
      specific to restaurant brands or service model: family-style restaurants reduced
      sodium among higher-sodium entrees at the 75th percentile, but not on average,
      and entrees still far exceeded recommended limits. Fast-food restaurants
      decreased mean energy in children's menu entrees by 40 kcal. A few individual
      restaurant brands made significant changes in energy or sodium, but the vast
      majority did not, and not all changes were in the healthier direction. Among
      those brands that did change, there were slightly more brands that reduced energy
      and sodium compared with those that increased it. CONCLUSIONS: Industry marketing
      and pledges may create a misleading perception that restaurant menus are becoming
      substantially healthier, but both healthy and unhealthy menu changes can occur
      simultaneously. Our study found no meaningful changes overall across a 1-year
      time period. Longer-term studies are needed to track changes over time,
      particularly after the federal menu labeling law is implemented.

PMID- 24095623
TI  - Vasoplegia in septic shock: do we really fight the right enemy?
AB  - Vasoplegia is a key factor for the death of patients with septic shock in
      intensive care unit owing to persistent and irreversible hypotension. Impairment
      of vascular reactivity has been attributed to a combination of endothelial
      injury, arginine-vasopressin system dysfunction, release of other vasodilatory
      inflammatory mediators, and muscle hyperpolarizaton. Nitric oxide induced by a
      Ca(+2) independent isoform of nitric oxide synthase has been suggested to play an
      important role in sepsis-induced vasoplegia. However, inhibition of nitric oxide
      synthase only partially restores the endotoxin-induced vascular hyporeactivity.
      The aim of this review is to discuss in detail the recent suggested alternative
      mechanisms of vasoplegia and to briefly outline the current therapeutic
      strategies and the novel therapeutic options based on those mechanisms. 

PMID- 24095624
TI  - Quantitative real-time PCR and phase specific serology are mutually supportive in
      Q fever diagnostics in goats.
AB  - This study presents results of quantitative pathogen detection by real-time PCR
      (qPCR) and phase-specific serology for complete Q fever diagnostics. For this,
      samples of 42 goats in total were taken during a Q fever outbreak. In the early
      phase of the Q-fever infection, 10(4)-10(8)Coxiella (C.) burnetii pathogens per
      vaginal swab and 10(2)-10(6)C. burnetii per ml milk were detected using
      quantitative real-time PCR (qPCR). Pathogen excretion decreased continuously
      within two months to less than 10(4) (vaginal swab) and 10(2) (milk) C. burnetii.
      At the end of the study there was a shift toward a 10 fold higher excretion of
      the pathogen via the genital tract and milk. At the start of the study,
      serological tests showed a dominance of the phase-2 antibody in 76% (22/29) of
      the goats in the MONA- (Multiple of Normal Activity) ELISA and 79% (23/29) in the
      IDEXX-ELISA, which was replaced by a phase-1 dominance in 85% (29/34) and 62%
      (21/34), of the animals respectively at the end of the study. Serum samples from
      13 goats before lambing that excreted C. burnetii after lambing showed antibodies
      against phase 2 of 100% using MONA-ELISA and 77% in the IDEXX-ELISA. The most
      important diagnostic instrument for Q-fever infection in goats following birth is
      testing of vaginal swabs using qPCR. Phase-specific serology allows an estimation
      of possible pathogen excretion even before birth, as well as achieving valuable
      results for determination of the infection phase. 

PMID- 24095625
TI  - Detection of a Hobi-like virus in archival samples suggests circulation of this
      emerging pestivirus species in Europe prior to 2007.
AB  - The first reported incidence of Hobi-like viruses in Europe dates to a 2010
      outbreak of respiratory disease in cattle in Italy. In this study, a Hobi-like
      virus was detected in archival samples, collected in 2007 in Italy from a cattle
      herd displaying respiratory disease, during the validation of a nested PCR
      protocol for rapid characterization of bovine pestiviruses. Phylogeny conducted
      with full-length pestivirus genomes and three informative genomic sequences,
      placed the strain detected in the samples, Italy-129/07, into the Hobi-like virus
      branch. Italy-129/07, similar to other Hobi-like viruses isolated in Italy, was
      more closely related to viruses of South American origin, than Hobi-like viruses
      of Southeast Asian origin. This suggests a possible introduction of this emerging
      group of pestiviruses into Italy as a consequence of using contaminated
      biological products such as fetal bovine serum originating in South America. This
      report of a Hobi-like virus associated with respiratory disease along with the
      full-genomic characterization of the virus detected provides new data that
      contributes to the body of knowledge regarding the epidemiology, pathobiology and
      genetic diversity of this emerging group of pestiviruses. Importantly, it dates
      the circulation of Hobi-like viruses in Italy to 2007, at least three years
      before previous reports. 

PMID- 24095626
TI  - [Health status and intimate partner violence].
AB  - OBJECTIVE: To describe the prevalence of intimate partner violence (IPV) in Spain
      in the last year and at some point during the lifetime, to determine health
      status in women according to whether they had experienced IPV or not, and to
      analyze the individual variables associated with IPV in Spain. METHODS: A cross
      sectional study was performed of the database, Macrosurvey on Gender Violence in
      Spain 2011. This database includes data on 7,898 women older than 18 years old.
      The dependent variables were IPV-last year, IPV-ever in life. Covariates
      consisted of sociodemographic characteristics, socioeconomic status, maternal
      experience of IPV, social support, and self-care. The measure of association used
      was the OR with its 95% confidence interval (95% CI). RESULTS: A total of 3.6% of
      women had experienced IPV-last year and 12.2% ever in life. Female victims of IPV
      had poorer health than women who had not experienced IPV. Immigrant women living
      in Spain for 6 years or more were more likely to experience IPV-ever in life than
      Spanish women [OR (95% CI): 1.95 (1.50, 2.53)]. An interaction was found between
      nationality and the existence of children under 18 years old. Among women with
      children under 18 years old, immigrant women were more likely to experience IPV
      last year than Spanish women [OR (95% CI): 1.99 (1.25, 3.17)]. Other variables
      associated with IPV were age, low socioeconomic status, low social support and
      having a mother who had experienced IPV. CONCLUSIONS: In Spain, some women have a
      higher probability of experiencing IPV. The variables associated with greater
      vulnerability to IPV should be taken into account when implementing measures to
      prevent or alleviate IPV.

PMID- 24095627
TI  - [Reflections on the present and future of family medicine].

PMID- 24095628
TI  - The wobbly evidence base of reproductive medicine.
AB  - In assisted reproduction, there is strong evidence for some things done, but no
      or only very weak evidence for others. There are several reasons for this. Most
      assisted reproduction procedures have small signal-to-noise ratios. This means
      that their treatment effect is sometimes only little better than the spontaneous
      conception rate, or the conception rate with traditional treatment. Hence, large
      trials are required. These demand complex multicentre logistics. The latter
      require substantial funding and funding for reproductive medicine in most
      countries is notoriously difficult to obtain (as opposed, for example, to
      oncology research or cardiovascular research). Apart from these funding issues,
      the creation of embryos specifically for research is only allowed in a limited
      number of European countries, thus tempting clinicians to skip preclinical
      studies altogether and go directly for clinical application in their patients,
      raising an ethical issue. Introducing new treatments into the clinic without
      proper evidence, however, is perhaps even more of an ethical issue. Subfertile
      couples are very vulnerable and should not be exploited.

PMID- 24095629
TI  - Use of Web-based training for quality improvement between a field
      immunohistochemistry laboratory in Nigeria and its United States-based partner
      institution.
AB  - The importance of hormone receptor status in assigning treatment and the
      potential use of human epidermal growth factor receptor 2 (HER2)-targeted therapy
      have made it beneficial for laboratories to improve detection techniques. Because
      interlaboratory variability in immunohistochemistry (IHC) tests may also affect
      studies of breast cancer subtypes in different countries, we undertook a Web
      based quality improvement training and a comparative study of accuracy of
      immunohistochemical tests of breast cancer biomarkers between a well-established
      laboratory in the United States (University of Chicago) and a field laboratory in
      Ibadan, Nigeria. Two hundred and thirty-two breast tumor blocks were evaluated
      for estrogen receptors (ERs), progesterone receptors (PRs), and HER2 status at
      both laboratories using tissue microarray technique. Initially, concordance
      analysis revealed kappa scores of 0.42 (moderate agreement) for ER, 0.41
      (moderate agreement) for PR, and 0.39 (fair agreement) for HER2 between the 2
      laboratories. Antigen retrieval techniques and scoring methods were identified as
      important reasons for discrepancy. Web-based conferences using Web conferencing
      tools such as Skype and WebEx were then held periodically to discuss IHC staining
      protocols and standard scoring systems and to resolve discrepant cases. After
      quality assurance and training, the agreement improved to 0.64 (substantial
      agreement) for ER, 0.60 (moderate agreement) for PR, and 0.75 (substantial
      agreement) for HER2. We found Web-based conferences and digital microscopy useful
      and cost-effective tools for quality assurance of IHC, consultation, and
      collaboration between distant laboratories. Quality improvement exercises in
      testing of tumor biomarkers will reduce misclassification in epidemiologic
      studies of breast cancer subtypes and provide much needed capacity building in
      resource-poor countries.

PMID- 24095630
TI  - Chromophobe renal cell carcinoma: a morphologic and immunohistochemical study of
      45 cases.
AB  - The aim of this study was to evaluate the morphological spectrum of chromophobe
      renal cell carcinoma (CRCC) and diagnostic utility of a panel of three
      immunohistochemical stains. All cases of CRCC reported between 2002 and 2012 in
      the Section of Histopathology, Aga Khan University Hospital, were retrieved. A
      total of 45 cases were identified. Slides were reviewed and immunohistochemical
      stains (CK7, CD117, and vimentin) were performed. Ages ranged from 18 to 90 years
      (mean, 48.5 years). Male-to-female ratio was 0.8:1. The tumor was located in the
      left kidney in 24 patients and the right kidney in 20 patients. The tumor size
      ranged from 3.5 to 22 cm (mean 10 cm). Histologically, 4 were classic, 22 were
      eosinophilic, 16 were mixed, and 3 were sarcomatoid type. Morphologic patterns
      included broad alveolar, solid, nested, tubular, tubulocystic, trabecular,
      papillary, and microglandular. Binucleation and perinuclear halos were seen in
      all cases. Nuclear grooves and pseudoinclusions were seen in 17 and 6 cases,
      respectively. Multinucleated cells were seen in 19 cases. Mitoses ranged from 1
      to 11/10 HPFs (mean 3/10 HPFs). Hyalinized stroma was seen in 38 cases and
      calcification in 26 cases. Necrosis was seen in 18 cases. Palisading of smaller
      cells around the broad alveolar pattern was noted in 5 cases. The Furhman's
      nuclear grade was I (11), II (26), III (5), and IV (3). Hale's colloidal iron was
      positive in all cases. Immunohistochemical stain CK7 and CD117 were positive in
      100% and 95.5% of cases respectively. Vimentin was negative in all cases, except
      in the sarcomatoid areas of 3 cases. In conclusion, chromophobe renal cell
      carcinoma has certain unique morphological features and immunohistochemical
      profile which help to distinguish it from conventional renal cell carcinoma and
      oncocytoma. We identified nuclear pseudoinclusions, microglandular pattern and
      palisading of smaller cells, which have not been reported earlier.

PMID- 24095631
TI  - Aldosterone and parathyroid hormone interactions as mediators of metabolic and
      cardiovascular disease.
AB  - Inappropriate aldosterone and parathyroid hormone (PTH) secretion is strongly
      linked with development and progression of cardiovascular (CV) disease.
      Accumulating evidence suggests a bidirectional interplay between parathyroid
      hormone and aldosterone. This interaction may lead to a disproportionally
      increased risk of CV damage, metabolic and bone diseases. This review focuses on
      mechanisms underlying the mutual interplay between aldosterone and PTH as well as
      their potential impact on CV, metabolic and bone health. PTH stimulates
      aldosterone secretion by increasing the calcium concentration in the cells of the
      adrenal zona glomerulosa as a result of binding to the PTH/PTH-rP receptor and
      indirectly by potentiating angiotensin 2 induced effects. This may explain why
      after parathyroidectomy lower aldosterone levels are seen in parallel with
      improved cardiovascular outcomes. Aldosterone mediated effects are
      inappropriately pronounced in conditions such as chronic heart failure, excess
      dietary salt intake (relative aldosterone excess) and primary aldosteronism. PTH
      is increased as a result of (1) the MR (mineralocorticoid receptor) mediated
      calciuretic and magnesiuretic effects with a trend of hypocalcemia and
      hypomagnesemia; the resulting secondary hyperparathyroidism causes myocardial
      fibrosis and disturbed bone metabolism; and (2) direct effects of aldosterone on
      parathyroid cells via binding to the MR. This adverse sequence is interrupted by
      mineralocorticoid receptor blockade and adrenalectomy. Hyperaldosteronism due to
      klotho deficiency results in vascular calcification, which can be mitigated by
      spironolactone treatment. In view of the documented reciprocal interaction
      between aldosterone and PTH as well as the potentially ensuing target organ
      damage, studies are needed to evaluate diagnostic and therapeutic strategies to
      address this increasingly recognized pathophysiological phenomenon. 

PMID- 24095632
TI  - Head-to-head comparison of fibrates versus statins for elevation of circulating
      adiponectin concentrations: a systematic review and meta-analysis.
AB  - BACKGROUND: Elevation of adiponectin levels is a potential therapeutic tool
      against cardiovascular and metabolic diseases. Clinical evidence suggests
      differences between fibrates and statins in improving circulating concentrations
      of adiponectin. AIM: To compare the efficacy of fibrates vs. statins on
      circulating concentrations of adiponectin by meta-analysis of randomized head-to
      head trials. METHODS: A systematic literature search of Medline was conducted to
      identify randomized head-to-head comparative trials investigating the efficacy of
      fibrates vs. statins on circulating levels of adiponectin. Inverse variance
      weighted mean differences (WMDs) and 95% confidence intervals (CIs) were
      calculated for net changes in adiponectin concentrations using a random-effects
      model. Random-effects meta-regression was performed to assess the effect of
      putative moderators on adiponectin levels. RESULTS: Six trials with a total of
      326 subjects (166 in the fibrate and 160 in the statin group) met the eligibility
      criteria and were selected for this meta-analysis. The estimated effect size for
      fibrate versus statin therapy was 0.42 MUg/mL (95% CI: -0.34-1.17). This effect
      size was robust in the leave-one-out sensitivity analysis and not sensitive to
      any single study. Meta-regression indicated a borderline significant association
      between duration of treatment and the effect of fibrates vs. statins on
      adiponectin concentrations (slope: -0.20; 95% CI: -0.41-0.01; p=0.06). However,
      baseline body mass index, glucose and lipid levels did not predict the effect of
      fibrate vs. statin therapy on circulating adiponectin concentrations (p>0.05).
      CONCLUSIONS: Monotherapy with either fibrates or statins has comparable effects
      on circulating concentrations of adiponectin. Thus, differential effects of
      statins and fibrates on the occurrence of cardiovascular events may not be
      attributed to the corresponding changes in adiponectin levels.

PMID- 24095636
TI  - [Target volumes in cervical lympadenopathies of unknown primary: toward a
      selective customized approach? On behalf of REFCOR].
AB  - The treatment of carcinomas of unknown primary revealed by cervical
      lymphadenopathy is based on neck dissection and nodal and pan-mucosal irradiation
      to control the neck and avoid the emergence of a metachronous primary. The aim of
      this review was to assess diagnostic and therapeutic approaches and criteria that
      may be used for a customized selective approach to avoid severe toxicities of pan
      mucosal irradiation. A literature search was performed with the following
      keywords: cervical lymphadenopathy, unknown primary, upper aerodigestive tract,
      cancer, radiotherapy, squamous cell carcinoma, variants. The diagnostic workup
      includes a head and neck scanner or MRI, ((18)F)-FDG PET CT, a panendoscopy and
      tonsillectomy. Squamous cell carcinoma represents over two thirds of cases. The
      number of metastatic cervical nodes, nodal level, and histological variant
      (associated with HPV/EBV status) may determine the primary site origin and might
      be weighted for the determination of radiation target volumes on a
      multidisciplinary basis. A selective customized approach is relevant to decrease
      radiation toxicity only if neck and mucosal control is not impaired. Although no
      recommendation can yet be made in the absence of sufficient level of evidence,
      the relevance of systematic pan-mucosal irradiation appears questionable in a
      number of clinical situations. Accordingly, a customized selective redefinition
      of target volumes may be discussed and be prospectively evaluated in relation to
      the therapeutic index obtained. 

PMID- 24095637
TI  - Revisiting the chronology of the Proto-Aurignacian and the Early Aurignacian in
      Europe: a reply to Higham et al.'s comments on Banks et al. (2013).

PMID- 24095638
TI  - Glutamine supplementation, but not combined glutamine and arginine
      supplementation, improves gut barrier function during chemotherapy-induced
      intestinal mucositis in rats.
AB  - BACKGROUND & AIMS: Increased intestinal permeability occurs during chemotherapy
      induced intestinal mucositis. Previous data suggest that glutamine and arginine
      may have additive or synergic effects to limit intestinal damage. The present
      study aimed to evaluate the effects of glutamine and arginine, each alone or in
      combination, on gut barrier function during methotrexate (MTX)-induced mucositis
      in rats. METHODS: Eighty Sprague Dawley rats received during 7 days (d) standard
      chow supplemented with protein powder (PP), glutamine (G, 2%), arginine (A, 1.2%)
      or glutamine plus arginine (GA). All diets were isonitrogenous. Rats received
      subcutaneous injections of MTX (2.5 mg/kg) from d0 to d2. The intestinal
      permeability and tight junction proteins were assessed at d4 and d9 in the
      jejunum by FITC-dextran and by western blot and immunohistochemistry,
      respectively. RESULTS: At d4, intestinal permeability was increased in MTX-PP,
      MTX-A and MTX-GA rats compared with controls but not in MTX-G rats. The
      expression of claudin-1, occludin and ZO-1 was decreased in MTX-PP group compared
      with controls but was restored in MTX-G and MTX-A rats. In MTX-GA rats, occludin
      expression remained decreased. These effects could be explained by an increase of
      erk phosphorylation and a decrease of IkappaBalpha expression in MTX-PP and MTX
      GA rats. At d9, Intestinal permeability remained higher only in MTX-GA rats. This
      was associated with a persistent decrease of occludin expression. CONCLUSIONS:
      Glutamine prevents MTX-induced gut barrier disruption by regulating occludin and
      claudin-1 probably through erk and NF-kappaB pathways. In contrast, combined
      glutamine and arginine has no protective effect in this model.

PMID- 24095639
TI  - Surrogate end points and postprogression survival in renal cell carcinoma: an
      analysis of first-line trials with targeted therapies.
AB  - Our end point was to determine the correlations between progression-free survival
      (PFS), postprogression survival (PPS), response rate (RR), and disease control
      rate (DCR) (RR + stable disease) and overall survival (OS) in first-line trials
      of renal cell carcinoma (RCC) treated with targeted therapies and to identify a
      potential surrogate for OS. Data were collected from first-line phase III
      randomized trials in RCC. Linear regression was undertaken to evaluate the
      correlations between end points and a potential surrogate end point for OS. Six
      randomized trials were identified containing a total of 7 treatment arms. The
      nonparametric Spearman rank correlation coefficients (r(s)) between PFS, PPS, and
      RR/DCR and OS are 0.869, and 1, 0.96/1 (all P < .0001), respectively. There is a
      strong relationship between differences (Delta) in DCR and DeltaOS (r(s) = 1).
      The slope of the regression line is 0.3963 +/- 0.0019, indicating that a novel
      drug producing a 10% increase for DCR will yield an estimated absolute 3.9%
      increase in OS. In first-line trials including novel targeted agents for RCC, PFS
      is a relatively flawed surrogate end point because of PPS influence. Improvement
      in DCR is strongly associated with improvement in median OS. In this population,
      DCR may be an appropriate surrogate for OS.

PMID- 24095640
TI  - Infrastructure and resources for an aging population: embracing complexity in
      translational research.
AB  - The population of the United States and most industrialized nations is undergoing
      rapid expansion of persons aged 65 years and older. This group experiences more
      illness, disability, and dependency than young adults and consumes the majority
      of heath care resources. This demographic change presents a number of challenges
      to current research infrastructure aimed at translating discoveries to improved
      human health. Key issues include the need to expand the workforce trained in
      aging research, development of specific resources and harmonization of measures
      and outcomes, and a culture change within the scientific community. In
      particular, complexity must be represented within research design and embraced as
      an important aspect of review panel critiques. 

PMID- 24095641
TI  - Blood banking and transfusion medicine in extreme or resource-limited conditions.

PMID- 24095642
TI  - Sensitive and specific detection of enteropathogenic and enterohemorrhagic
      Escherichia coli using recombinant anti-intimin antibody by immunofluorescence
      assay.
AB  - The main and common virulence factor expressed by enteropathogenic Escherichia
      coli (EPEC) and enterohemorrhagic E. coli (EHEC) is intimin, a 94-kDa outer
      membrane protein, which is a product of the eae gene, and, thus, an excellent
      target for the detection of these pathogens. Among the methods for detection of
      virulence factor expression, immunoassays can be considered the first alternative
      to either animal use or in vitro culture cells assays, for which polyclonal
      and/or monoclonal antibodies are raised. In the present work, we evaluated the
      sensitivity and specificity of an intimin recombinant antibody (scFv-intimin)
      using immunofluorescence assay. The scFv-intimin detected typical EPEC, atypical
      EPEC, and EHEC isolates (100% sensitivity) with no detection of eae- isolates
      (100% specificity). Thus, immunofluorescence is an effective and rapid method,
      and scFv-intimin, an excellent tool for the diagnosis of diarrhea caused by EPEC
      and EHEC and also can be employed in case-control epidemiological surveys. 

PMID- 24095643
TI  - Linezolid resistance in Enterococcus faecium isolated in Ontario, Canada.
AB  - Recent studies have described linezolid-resistant MRSA and vancomycin-resistant
      enterococci (VRE) occurring worldwide, including an outbreak of linezolid
      resistant MRSA. The objective of this study was to determine if linezolid
      resistant enterococci are present in clinical isolates in Ontario, Canada. From
      January 2010 to June 2012, all enterococcal isolates submitted to the Public
      Health Ontario Laboratory (PHOL) for confirmation of VRE and susceptibility
      testing were included in this study. Of 2829 enterococcal isolates tested, 12
      Enterococcus faecium were found to be resistant to linezolid. All linezolid
      resistant isolates were also resistant to ampicillin, ciprofloxacin, and
      vancomycin. In addition, 33% of isolates were non-susceptible to daptomycin,
      whereas 41% were resistant to quinupristin/dalfopristin. Molecular
      characterization of these isolates showed that 8/12 isolates (66.7%) contained
      the mutation G2576T in 23S rRNA, which has been associated with linezolid
      resistance. Amplification and sequencing of L3- and L4-coding genes did not
      reveal mutations associated with linezolid resistance. One isolate contained the
      cfr gene, which is associated with linezolid resistance, and has been found in
      staphylococcal species and E. faecalis. These data show that occurrence of
      linezolid resistance is still rare among enterococcal isolates referred to PHOL
      though detection of cfr in E. faecium is concerning as it has the potential to
      disseminate among other enterococci. 

PMID- 24095644
TI  - Effect of eugenol-containing and resin endodontic sealers on retention of
      prefabricated metal posts cemented with zinc phosphate and resin cements.
AB  - PURPOSE: The aim of this study was to compare the effects of two endodontic
      sealers on the retention of posts cemented with zinc phosphate or resin cement.
      MATERIALS AND METHODS: Crowns of 72 mandibular premolars were removed at the
      cementoenamel junction. Root canals were prepared and specimens were randomly
      divided into two groups of 36. In each group, 12 specimens were obturated with
      gutta percha only; 12 specimens with gutta percha/ZOE sealer and 12 specimens
      with gutta percha/AH26. In the first group, 10mm Post spaces were prepared with
      Peeso reamers size 4 and, size 5 stainless steel Paraposts were cemented in with
      zinc phosphate. In the second group, 10mm Post spaces were prepared with Fiber
      Lux size 5.5 drills and size 5 Paraposts were cemented with Panavia F2.0. After
      mounting in resin blocks, posts were pulled out by universal testing machine at
      1mm/min and results were analyzed by two-way ANOVA and Dunnett test. RESULTS:
      Mean forces (in Newtons) required to remove posts cemented with zinc phosphate in
      canals obturated without sealer, with ZOE, and with AH26 sealers were 270+/-83,
      281+/-128 and 266+/-67, respectively; and for posts cemented with Panavia F2.0
      were 520+/-290, 464+/-212 and 229+/-108, respectively. Statistical analysis
      showed that AH26 significantly reduced retention of posts cemented with Panavia
      F2.0 (p<0.05). CONCLUSION: Different sealers had no significant effect on
      retention of posts cemented with zinc phosphate. However posts cemented with
      Panavia F2.0 showed reduced retention in canals obturated with AH26.

PMID- 24095645
TI  - PACAP modulates GnRH signaling in gonadotropes.
AB  - Hypothalamic gonadotropin-releasing hormone is known to be critical for normal
      gonadotropin biosynthesis and secretion by the gonadotrope cells of the anterior
      pituitary gland. Additional regulation is provided by gonadal steroid feedback as
      well as by intrapituitary factors, such as activin and follistatin. Less well
      appreciated is the role of pituitary adenylate-cyclase activating polypeptide
      (PACAP) as both a hypothalamic-pituitary releasing factor as well as an autocrine
      paracrine factor within the pituitary. PACAP regulates gonadotropin expression
      alone and through modulation of GnRH responsiveness achieved by increases in GnRH
      receptor expression and interactions at the level of intracellular signaling
      pathways. In addition to direct effects on the gonadotrope, PACAP stimulates
      follistatin secretion by the folliculostellate cells and thereby contributes to
      differential expression of the gonadotropin subunits. Conversely, GnRH augments
      the ability of PACAP to regulate gonadotrope function by increasing pituitary
      PACAP and PACAP receptor expression. This review will summarize the current
      understanding of the mechanisms by which PACAP modulates gonadotrope function,
      with a focus on interactions with GnRH. 

PMID- 24095646
TI  - Clinical insights from adiponectin analysis in breast cancer patients reveal its
      anti-inflammatory properties in non-obese women.
AB  - Adiponectin is a cytokine reported as a determinant of poor prognosis in women
      with breast cancer. However, because data regarding its role in breast cancer
      have been obtained primarily from studies employing overweight or obese women,
      the adiponectin profile in non-obese women is poorly understood. In this study,
      we determined adiponectin levels in plasma from non-obese women with breast
      cancer and investigated a possible correlation with systemic inflammatory status.
      We determined the plasma adiponectin levels as well as biochemical and oxidative
      stress parameters in 80 women. Our results revealed that plasma adiponectin
      levels were affected by chemotherapy, estrogen receptor status, and disease
      progression. Adiponectin was positively correlated with antioxidant levels,
      without affecting either the metastatic behavior of disease or patient outcome.
      These findings highlight adiponectin as a novel player in the endocrine signaling
      that modulates the oxidative inflammatory response in human breast cancer, and
      contribute to the understanding of the role of adiponectin in pathological
      conditions in non-obese women. 

PMID- 24095647
TI  - Stroke by carotid artery complete occlusion in Kawasaki disease: case report and
      review of literature.
AB  - BACKGROUND: Kawasaki disease is an acute and time-limited systemic vasculitis
      primarily affecting young children. PATIENT: We describe an 18-month-old girl
      with Kawasaki disease who developed cerebral infarction following complete
      occlusion of her right internal carotid artery. RESULTS: The occlusion occurred
      10 days after the onset of fever, while she was on high-dose aspirin, and the day
      after she received intravenous immunoglobulin treatment. We present the first
      literature review on this very rare complication. CONCLUSION: Stroke is a rare
      neurological complication in Kawasaki disease. Optimal treatment should be begun
      as soon as possible after diagnosis. Intravenous immunoglobulins seem to reduce
      the cerebrovascular complications, but evaluation of hydration status is strongly
      recommended before performing such treatment.

PMID- 24095648
TI  - Morning glory optic disc anomaly.

PMID- 24095649
TI  - Functional role of the MrpA- and MrpD-homologous protein subunits in enzyme
      complexes evolutionary related to respiratory chain complex I.
AB  - NADH:quinone oxidoreductase or complex I is a large membrane bound enzyme complex
      that has evolved from the combination of smaller functional building blocks.
      Intermediate size enzyme complexes exist in nature that comprise some, but not
      all of the protein subunits in full size 14-subunit complex I. The membrane
      spanning complex I subunits NuoL, NuoM and NuoN are homologous to each other and
      to two proteins from one particular class of Na(+)/H(+) antiporters, denoted MrpA
      and MrpD. In complex I, these ion transporter protein subunits are prime
      candidates for harboring important parts of the proton pumping machinery. Using a
      model system, consisting of Bacillus subtilis MrpA and MrpD deletion strains and
      a low copy expression plasmid, it was recently demonstrated that NuoN can rescue
      the strain deleted for MrpD but not that deleted for MrpA, whereas the opposite
      tendency was seen for NuoL. This demonstrated that the MrpA-type and MrpD-type
      proteins have unique functional specializations. In this work, the corresponding
      antiporter-like protein subunits from the smaller enzymes evolutionarily related
      to complex I were tested in the same model system. The subunits from 11-subunit
      complex I from Bacillus cereus behaved essentially as those from full size
      complex I, corroborating that this enzyme should be regarded as a bona fide
      complex I. The hydrogenase-3 and hydrogenase-4 antiporter-like proteins on the
      other hand, could substitute equally well for MrpA or MrpD at pH7.4, suggesting
      that these enzymes have intermediate forms of the antiporter-like proteins, which
      seemingly lack the functional specificity. 

PMID- 24095650
TI  - Class I PI 3-kinases signaling in platelet activation and thrombosis:
      PDK1/Akt/GSK3 axis and impact of PTEN and SHIP1.
AB  - Class I phosphoinositide 3-kinases (PI3K) have been extensively studied in
      different models these last years and several isoforms are now promising drug
      targets to treat cancer and immune diseases. Blood platelets are non-nucleated
      cells critical for hemostasis and strongly involved in arterial thrombosis, a
      leading cause of death worldwide. Besides their role in hemostasis and
      thrombosis, platelets provide an interesting model to characterize the
      implication of the different isoforms of PI3K in signaling. They are specialized
      for regulated adhesion, particularly under high shear stress conditions found in
      arteries and use highly regulated signaling mechanisms to form and stabilize a
      thrombus. In this review we will highlight the role of class I PI3K in these
      processes and the pertinence of targeting them in the context of antithrombotic
      strategies but also the potential consequences on the bleeding risk of inhibiting
      the PI3K signaling in cancer therapy. The implication of upstream regulators of
      the most important isoforms of PI3K in platelets and their downstream effectors
      such as protein kinase B (PKB or Akt) and its target glycogen synthase kinase 3
      (GSK3) will be discussed as well as the impact of PTEN and SHIP phosphatases as
      modulators of this pathway. 

PMID- 24095652
TI  - A simple and convenient synthetic route to Ulipristal acetate.
AB  - We set out to describe a new and efficient route for preparing Ulipristal acetate
      with a good yield. The selected epoxidization conditions gave out 80% of
      5alpha,10alpha-epoxide 2a in the two diastereoisomers which greatly improved the
      yield of 11beta-substituted isomer 4a. And phenyl-sulfinyl compound 6 was
      synthesized from ketone 5 directly treated with phenylsulfenyl chloride in the
      presence of triethylamine. These synthetic procedures is only 8 steps, less than
      currently reported in the literature, but more suitable for industrial process. 

PMID- 24095651
TI  - Body image in social anxiety disorder, obsessive-compulsive disorder, and panic
      disorder.
AB  - Body dysmorphic disorder falls under the category of obsessive-compulsive and
      related disorders, yet research has suggested it may also be highly associated
      with social anxiety disorder. The current study examined body image variables
      among 68 outpatients with primary obsessive-compulsive disorder (OCD; n=22),
      social anxiety disorder (SAD; n=25), and panic disorder (PD; n=21). Participants
      filled out self-report measures of body image disturbance, attitudes toward one's
      appearance, and anxiety. Body image disturbance and attitudes toward appearance
      did not significantly differ between the groups. However, SAD symptoms predicted
      body image disturbance, Appearance Evaluation and Body Areas Satisfaction, and
      OCD symptoms predicted Appearance Orientation. These findings suggest that SAD
      and OCD may be associated with different facets of body image. Implications for
      the treatment of anxiety disorders and for future research are discussed. 

PMID- 24095653
TI  - Typical takotsubo cardiomyopathy in suspected ST elevation myocardial infarction
      patients admitted for primary percutaneous coronary intervention.
AB  - AIM: Takotsubo cardiomyopathy (TCM) is increasingly being recognised in patients
      admitted with suspected acute coronary syndrome, as access to angiography and
      echocardiography is much quicker than before. We aimed to analyse the prevalence
      of typical TCM in patients admitted for primary percutaneous coronary
      intervention (PPCI) with suspected ST elevation myocardial infarction (STEMI) to
      a single tertiary centre in United Kingdom. METHODS: All patients admitted to our
      unit with suspected STEMI from September 2009 to November 2011 were included for
      analysis. RESULTS: Of the 1875 patients admitted, 17 patients (all female) with
      mean age of 69+/-11.9 yrs were identified to have clinical features of typical
      TCM, thus giving an overall prevalence of 0.9% in PPCI admissions (3.2%
      prevalence in women). The admission ECG showed ST elevation in 14 patients (82%)
      and 3 had LBBB (18%). In the 16 patients who had raised hs Troponin (normal range
      <14), the mean level was 921+/-668 (median 778, range 110 to 2550) ng/L. Two
      patients survived cardiac arrest and one had apical thrombus on presentation.
      Left ventricular function was severely impaired (EF <=30%) in 2 patients, whilst
      it was moderately impaired (EF 31-50%) in others. During a mean follow-up period
      of 22+/-7 months (range 8-36 months), there was no mortality or recurrence.
      CONCLUSION: This is the first observational study to report the prevalence of
      typical TCM in patients admitted for PPCI in "real-world" practice. Though this
      condition is not benign during the acute episode, there is a good survival
      outcome if managed appropriately during the acute phase.

PMID- 24095654
TI  - Association of adiponectin with peripheral muscle status in elderly patients with
      heart failure.
AB  - BACKGROUND: Reduced peripheral muscle mass was demonstrated in patients with
      chronic heart failure (HF). Adipokines may have potent metabolic effects on
      skeletal muscle. The associations between adipokines, peripheral muscle mass, and
      muscle function have been poorly investigated in patients with HF. METHODS: We
      measured markers of fat and bone metabolism (adiponectin, leptin, 25-hydroxy
      vitamin D, parathyroid hormone, osteoprotegerin, RANKL), N-terminal pro B-type
      natriuretic peptide (NT-pro-BNP) in 73 non-cachectic, non-diabetic, male patients
      with chronic HF (age: 68 +/- 7 years, New York Heart Association class II/III:
      76/26%, left ventricular ejection fraction 29 +/- 8%) and 20 healthy controls of
      similar age. Lean mass as a measure of skeletal muscle mass was measured by dual
      energy X-ray absorptiometry (DEXA), while muscle strength was assessed by hand
      grip strength measured by Jamar dynamometer. RESULTS: Serum levels of
      adiponectin, parathyroid hormone, osteoprotegerin, RANKL, and NT-pro-BNP were
      elevated in patients with chronic HF compared to healthy controls (all p<0.0001),
      while no difference in serum levels of leptin, testosterone or SHBG was noted.
      Levels of 25-hydroxy vitamin D were reduced (p=0.002) in HF group. Peripheral
      lean mass and hand grip strength were reduced in patients with HF compared to
      healthy subjects (p=0.006 and p<0.0001, respectively). Using backward selection
      multivariable regression, serum levels of increased adiponectin remained
      significantly associated with reduced arm lean mass and muscle strength.
      CONCLUSIONS: Our findings may indicate a cross-sectional metabolic association of
      increased serum adiponectin with reduced peripheral muscle mass and muscle
      strength in non-cachectic, non-diabetic, elderly HF patients.

PMID- 24095655
TI  - Moderate lead exposure and elementary school end-of-grade examination
      performance.
AB  - PURPOSE: This study investigated the association between moderate lead poisoning
      in early childhood with performance on a comprehensive set of end-of-grade
      examinations at the elementary school level in two urban school districts.
      METHODS: Children born between 1996 and 2000 who resided in Milwaukee or Racine,
      WI, with a record of a blood lead test before the age of 3 years were considered
      for the analysis. Children were defined as exposed (blood lead level >=10 and <20
      MUg/dL) or not exposed (BLL < 5 MUg/dL). Parents of eligible children were mailed
      surveys to consent to participation and elicit information on potential
      confounders. On consent, children were matched to educational records for fourth
      grade Wisconsin Knowledge and Concepts Examinations. Seemingly unrelated
      regression was used to evaluate the relation between scaled scores on all
      sections of the examination (math, reading, language arts, science, and social
      studies) with exposure status, controlling for demographics, social status
      indicators, health indicators, and district-based poverty indicators. RESULTS: A
      total of 1133 families responded to the survey and consented to have educational
      records released; 43% of children were considered exposed. After controlling for
      demographic and socioeconomic covariates, lead exposure was associated with
      significantly lower scores in all sections of the Wisconsin Knowledge and
      Concepts Examinations (range: science, beta = -5.21, P = .01; reading, beta = 
      8.91, P = .003). Children who were black, had a parent with less than a high
      school education, and were classified by parents as having less than excellent
      health had significantly lower performance on all examination components.
      CONCLUSIONS: Children with moderate lead poisoning in early childhood performed
      significantly lower on all components of elementary school end-of-grade
      examinations compared with unexposed children. Household level social status and
      childhood health indicators partially explain decreased examination scores.

PMID- 24095656
TI  - The prevalence of obesity is increased in patients with late compared with early
      onset psoriasis.
AB  - PURPOSE: We compared the clinical and epidemiologic characteristics of early and
      late onset psoriasis with an emphasis on potential differences in the
      comorbidities associated with each subtype. METHODS: An observational,
      multicenter study was performed, and associations between the age at the time of
      diagnosis and binary comorbidity outcomes were evaluated using multiple logistic
      regression analysis adjusted for age and other relevant confounders. RESULTS: An
      increased prevalence of positive family history, psoriatic arthritis, and
      depression was observed in patients with early onset psoriasis. On the other
      hand, late onset psoriasis was more frequently associated with obesity and
      elevated waist circumference compared with early onset form. Elderly psoriatic
      patients (at the age of 75 years) with late onset psoriasis are at an especially
      high risk for obesity compared with individuals at the same age with an early
      onset disease. CONCLUSIONS: The increased frequency of psoriasis in the family of
      early onset patients may suggest that manifestation of psoriasis at younger age
      is driven by strong genetic influence. However, such a remarkable association of
      abdominal obesity with late onset psoriasis may suggest that obesity can be one
      of the acquired factors that may predispose for the development of psoriasis in
      the elderly.

PMID- 24095657
TI  - Youth and young adults with spina bifida: their utilization of physician and
      hospital services.
AB  - OBJECTIVE: To describe current patterns of health care utilization of youth and
      young adults who have spina bifida (SB) and provide evidence to guide the
      development of health care for this growing population. DESIGN: We conducted a
      secondary analysis of health services utilization data from the Canadian
      Institute for Health Information to determine the rates and patterns of health
      care utilization, because comprehensive health care has been recognized as
      critical to positive health outcomes. SETTING: Participants were identified from
      6 publicly funded children's treatment centers. PARTICIPANTS: Health records from
      youth (n=164; age range, 13.0-17.9y) and adults (n=120; age range, 23.0-32.9y)
      with SB contributed to this study. INTERVENTIONS: Not applicable. MAIN OUTCOME
      MEASURES: The rates of outpatient physician visits and hospital admissions for
      the youth and adult groups were calculated. The proportion with a "medical home"
      was also calculated. RESULTS: The annual rates of outpatient physician visits per
      1000 persons were 8031 for youth and 8524 for adults with SB. These rates were
      approximately 2.9 and 2.2 times higher, respectively, than for their age-matched
      peers. On average, 12% of youth and 24% of adults with SB had a medical home. The
      annual rates of hospital admissions per 1000 persons were 329 for youth and 285
      for adults with SB. Rates of admissions were 19.4 and 12.4 times higher,
      respectively, for these groups than for the general population. CONCLUSIONS: It
      appears that persons with SB are accessing health services more often than their
      age-matched peers, and few have a medical home. We recommend that seamless
      medical care be provided to all adults with SB, coordinated by a primary care
      provider, to facilitate comprehensive care.

PMID- 24095659
TI  - bZIP transcription factor SmJLB1 regulates autophagy-related genes Smatg8 and
      Smatg4 and is required for fruiting-body development and vegetative growth in
      Sordaria macrospora.
AB  - Autophagy is a precisely controlled degradation process in eukaryotic cells,
      during which the bulk of the cytoplasm is engulfed by a double membrane vesicle,
      the autophagosome. Fusion of the autophagosome with the vacuole leads to
      breakdown of its contents, such as proteins and organelles, and the recycling of
      nutrients. Earlier studies of autophagic genes of the core autophagic machinery
      in the filamentous ascomycete Sordaria macrospora elucidated the impact of
      autophagy on fungal viability, vegetative growth and fruiting-body development.
      To gain further knowledge about the regulation of autophagy in S. macrospora, we
      analyzed the function of the bZIP transcription factor SmJLB1, a homolog of the
      Podospora anserina basic zipper-type transcription factor induced during
      incompatibility 4 (IDI-4) and the Aspergillus nidulans transcription factor jun
      like bZIP A (JlbA). Generation of the homokaryotic deletion mutant demonstrated
      S. macrospora Smjlb1 is associated with autophagy-dependent processes. Deletion
      of Smjlb1 abolished fruiting-body formation and impaired vegetative growth.
      SmJLB1 is localized to the cytoplasm and to nuclei. Quantitative real-time PCR
      experiments revealed an upregulated expression of autophagy-related genes Smatg8
      and Smatg4 in the Smjlb1 deletion mutant, suggesting a transcriptional repression
      function of SmJLB1. 

PMID- 24095658
TI  - Validation of QuickDASH outcome measure in breast cancer survivors for upper
      extremity disability.
AB  - OBJECTIVE: To validate the QuickDASH as a patient-reported outcome measure for
      assessing upper extremity disability in breast cancer survivors. DESIGN: Large
      cross-sectional survey. SETTING: Ambulatory care center at a university hospital.
      PARTICIPANTS: Postmenopausal women (N=150) with stage I to III hormone receptor
      positive breast cancer currently taking a third-generation aromatase inhibitor.
      INTERVENTIONS: Not applicable. MAIN OUTCOME MEASURE: QuickDASH, an 11-item self
      administered questionnaire, assesses global arm function over the past 7 days.
      RESULTS: Of 150 surveys, 148 (99%) were scorable. The factor analysis
      demonstrated 1 factor with an eigenvalue of 6.7, which explains 61% of variance.
      The score was reliable with a Cronbach alpha of .93. The test-retest reliability
      was .78 over 2 weeks. The mean QuickDASH score +/- SD for all patients was 19+/
      19. Those with upper extremity arthralgias reported higher QuickDASH scores than
      controls without pain (26 vs 12, P=.001). Those with frozen shoulder pain also
      reported higher QuickDASH scores than controls without pain (37 vs 15, P=.001).
      CONCLUSIONS: The QuickDASH instrument is a convenient, reliable, and valid
      patient-reported outcome measure to assess upper extremity disability in patients
      with breast cancer.

PMID- 24095660
TI  - Fungal meningitis outbreak editorial.

PMID- 24095661
TI  - Preparation of chitooligosaccharides from cicada slough and their antibacterial
      activity.
AB  - In this study, chitooligosaccharides were prepared from cicada slough of
      Cryptotympana atrata Fabricius by hydrolysis using hydrogen peroxide (H2O2).
      Factors affecting the hydrolysis of chitosan were investigated and the optimum
      hydrolysis conditions were as follows: time, 4 h; temperature, 65  degrees C;
      amount of H2O2, 2% (v/v); and pH, 5. Under these conditions, the average degree
      of polymerisation decreased to ~4.5. The Fourier transform infrared spectra and
      product sugar composition indicate that there were no significant chemical
      changes in the backbones of the chitosan treated with H2O2.The
      chitooligosaccharides had high antibacterial activity against Bacillus subtilis,
      Staphylococcus aureus, and Escherichia coli at the concentration of 100mg/mL.

PMID- 24095662
TI  - Effects of polysaccharide from pumpkin on biochemical indicator and pancreatic
      tissue of the diabetic rabbits.
AB  - A water-soluble polysaccharide (PCE-CC) was obtained from pumpkin which belongs
      to the family Cucubitaceae by the water and ethanol extract, organic solvent
      fractional extraction and deproteinization. The present study was designed to
      investigate PCE-CC possible mechanism underlying the improvement of damaged
      pancreatic islets. Alloxan-induced diabetic rabbits were injected with PCE-CC for
      21 days to assess effects on islet tissue morphology. After 21 days, the weights
      of the alloxan-induced diabetic and non-diabetic rabbits fed with diet contained
      PCE-CC were significantly increased as compared to the negative group. The data
      of blood glucose (BG), total cholesterol (TC), total triglyceride (TG) and
      glycosylated hemoglobin (HbA1c) indicated that PCE-CC had beneficial effects on
      the improvement in the control of blood glucose, serum lipid and glycosylated
      hemoglobin levels. Observing the pancreatic tissue of the diabetic rabbits
      revealed that PCE-CC could promote the regeneration of damaged pancreatic islets
      by stimulating beta-cell proliferation, which was accompanied by a decrease in
      plasma glucose levels. PCE-CC was further separated and purified to obtain PCE
      CCH by ion exchange and gel chromatography. PCE-CCH was a heteropolysaccharide
      and consisted of glucose, galactose, arabinose, rhamnose and little amount of
      hexuronic acid, with a molecular weight of 1.15 * 10(5) Da.

PMID- 24095663
TI  - Optimization of enzyme-assisted extraction of polysaccharides from alfalfa and
      its antioxidant activity.
AB  - In this present study, an efficient complex enzyme-assisted extraction technology
      was developed and optimized to extract polysaccharides from alfalfa using four
      factors at five levels central composite rotatable response surface design
      (CCRD). The experimental data was fitted to a second order polynomial equation
      with high coefficient of determination values (R(2)>0.95). The results of
      statistical analysis showed that the linear and quadratic terms of these four
      variables had significant effects (P<0.05) on the yield of polysaccharides from
      alfalfa. The optimum conditions were as follows: enzyme concentration of 2.5%,
      2.0%, 3.0% (weight of alfalfa) of cellulase, papain and pectase, extraction
      temperature 52.7  degrees C, extraction pH 3.87, ratio of water to raw material
      78.92 mL/g and extraction time 2.73 h. Under the optimal conditions, the
      experimental extraction yield of alfalfa polysaccharides was 5.05 +/- 0.02%,
      which was well matched with the value (5.09%) predicted by the CCRD model.
      Moreover, evaluation of the antioxidant activity of polysaccharides from alfalfa
      in vitro suggested that the polysaccharides had good antioxidant effect,
      especially scavenging activity for hydroxyl radical and DPPH radical, which
      indicated that the polysaccharides from alfalfa may be explored as a novel
      natural antioxidant.

PMID- 24095664
TI  - Novel dextran from Pediococcus pentosaceus CRAG3 isolated from fermented cucumber
      with anti-cancer properties.
AB  - The porous branched dextran of molecular mass 2.93 * 10(5) Da with 50% overall
      yield (4.5mg/ml) was produced from Pediococcus pentosaceus CRAG3 (GenBank ID:
      JX679020), a novel isolate from fermented cucumber. It contained glucose monomers
      linked through 75% alpha-(1,6) linkage with 25% (alpha-1,3) branching as
      displayed by spectroscopic analysis. The peak analysis showed alpha-(1,3)
      branching after every five glucose units of main chain. In vitro cytotoxicity
      analysis of dextran displayed anti-cancer activity against cervical cancer (HeLa)
      and colon cancer (HT29) cell lines opening new horizons in its pharmaceutical
      applications. Dextran showed enhanced growth of macrophage lines revealing its
      biocompatible nature.

PMID- 24095665
TI  - Action of jasmonates in plant stress responses and development--applied aspects.
AB  - Jasmonates (JAs) are lipid-derived compounds acting as key signaling compounds in
      plant stress responses and development. The JA co-receptor complex and several
      enzymes of JA biosynthesis have been crystallized, and various JA signal
      transduction pathways including cross-talk to most of the plant hormones have
      been intensively studied. Defense to herbivores and necrotrophic pathogens are
      mediated by JA. Other environmental cues mediated by JA are light, seasonal and
      circadian rhythms, cold stress, desiccation stress, salt stress and UV stress.
      During development growth inhibition of roots, shoots and leaves occur by JA,
      whereas seed germination and flower development are partially affected by its
      precursor 12-oxo-phytodienoic acid (OPDA). Based on these numerous JA mediated
      signal transduction pathways active in plant stress responses and development,
      there is an increasing interest in horticultural and biotechnological
      applications. Intercropping, the mixed growth of two or more crops,
      mycorrhization of plants, establishment of induced resistance, priming of plants
      for enhanced insect resistance as well as pre- and post-harvest application of JA
      are few examples. Additional sources for horticultural improvement, where JAs
      might be involved, are defense against nematodes, biocontrol by plant growth
      promoting rhizobacteria, altered composition of rhizosphere bacterial community,
      sustained balance between growth and defense, and improved plant immunity in
      intercropping systems. Finally, biotechnological application for JA-induced
      production of pharmaceuticals and application of JAs as anti-cancer agents were
      intensively studied. 

PMID- 24095666
TI  - Microparticle drug sequestration provides a parallel pathway in the acquisition
      of cancer drug resistance.
AB  - Expanding on our previous findings demonstrating that microparticles (MPs) spread
      cancer multidrug resistance, we now show that MPs sequester drugs, reducing the
      free drug concentration available to cells. MPs were isolated from drug-sensitive
      and drug-resistant sub-clones of a human breast adenocarcinoma cell line and from
      human acute lymphoblastic leukemia cells. MPs were assessed for size,
      mitochondria, RNA and phospholipid content, P-glycoprotein (P-gp) expression and
      orientation and ATPase activity relative to drug sequestration capacity. Of the
      drug classes examined, MPs sequestered the anthracycline class to a significant
      degree. The degree of sequestration was likely due to the size of MPs and thus
      the amount of cargo they contain, to which the anthracyclines bind. Moreover, a
      proportion of the P-gp present on MPs was inside-out in orientation, enabling it
      to influx drugs rather than its typical efflux function. This was confirmed by
      surface immunofluorescence and by assessment of drug-stimulated ATPase activity
      following MP permeabilization. Thus we determined that breast cancer MPs carried
      a proportion of their P-gp oriented inside-out, providing active sequestration
      within the microvesicular compartment. These results demonstrate a capacity for
      MPs to sequester chemotherapeutic drugs, which has a predominantly active
      sequestration component for MPs derived from drug-resistant cells and a
      predominantly passive component for MPs derived from drug-sensitive cells. This
      reduction in available drug concentration has potential to contribute to a
      parallel pathway and complements that of the intercellular transfer of P-gp.
      These findings lend further support to the role of MPs in limiting the successful
      management of cancer. 

PMID- 24095667
TI  - The chronic treatment in vivo of salicylate or morphine alters excitatory effects
      of subsequent salicylate or morphine tests in vitro in hippocampus area CA1.
AB  - The current practical tests were designed to study in vitro interactions in the
      field potential between salicylate and morphine analgesics in the hippocampus
      area CA1 taken from morphine-(7 days) or salicylate (6 days)-treated rats. For
      this, morphine or salicylate was applied in vitro to the hippocampal slices
      derived from chronically drug-treated or saline-injected rats and drug-induced
      changes in evoked field potentials of area CA1 were evaluated. Chronic treatment
      in vivo of morphine or salicylate had no impact on baseline field EPSP and
      population spikes (PS) but a leftward shift in fEPSP/PS (E/S) curves and an
      increase in paired pulse ratio at 10 ms IPI were seen. Acute in vitro salicylate
      produced a durable PS potentiation in morphine-treated group, whereas an increase
      in PS of all groups was observed after long-term exposure to in vitro salicylate.
      Acute in vitro morphine caused a stable PS potentiation in control and salicylate
      treated groups, but not in morphine treated group. A potentiated fEPSP and a
      greater PS potentiation in salicylate treated group were observed after long-term
      exposure to in vitro morphine. It is concluded that the chronic treatment in vivo
      of salicylate or morphine incites lasting changes in the CA1 circuitry, which
      alters excitatory effects of subsequent salicylate or morphine tests in vitro in
      a way that an increase in reactivity or tolerance to the acute salicylate or
      morphine administration was observed.

PMID- 24095668
TI  - Massive diverticulosis of the small intestine.

PMID- 24095669
TI  - ECAP spread of excitation with virtual channels and physical electrodes.
AB  - The primary goal of this study was to evaluate physiological spatial excitation
      patterns for stimulation of adjacent physical electrodes and intermediate virtual
      channels. Two experiments were conducted that utilized electrically evoked
      compound action potential (ECAP) spread-of-excitation (SOE) functions obtained
      with the traditional forward-masking subtraction method. These two experiments
      examined spatial excitation patterns for virtual-channel maskers and probes,
      respectively. In Experiment 1, ECAP SOE patterns were obtained for maskers
      applied to physical electrodes and virtual channels to determine whether virtual
      channel maskers yield SOE patterns similar to those predicted from physical
      electrodes. In Experiment 2, spatial separation of SOE functions was compared for
      two adjacent physical probe electrodes and the intermediate virtual channel to
      determine the extent to which ECAP SOE patterns for virtual-channel probes are
      spatially separate from those obtained with physical electrodes. Data were
      obtained for three electrode regions (basal, middle, apical) for 35 ears
      implanted with Cochlear (N = 16) or Advanced Bionics (N = 19) devices. Results
      from Experiment 1 showed no significant difference between predicted and measured
      ECAP amplitudes for Advanced Bionics subjects. Measured ECAP amplitudes for
      virtual-channel maskers were significantly larger than the predicted amplitudes
      for Cochlear subjects; however, the difference was <2 MUV and thus is likely not
      clinically significant. Results from Experiment 2 showed that the probe set in
      the apical region demonstrated the least amount of spatial separation amongst SOE
      functions, which may be attributed to more uniform nerve survival patterns,
      closer electrode spacing, and/or the tapered geometry of the cochlea. As
      expected, adjacent physical probes demonstrated greater spatial separation than
      for comparisons between each physical probe and the intermediate virtual channel.
      Finally, the virtual-channel SOE functions were generally weighted toward the
      basal electrode in the pair.

PMID- 24095670
TI  - Germacrone inhibits early stages of influenza virus infection.
AB  - Highly pathogenic influenza viruses pose a serious public health threat to
      humans. Although vaccines are available, antivirals are needed to efficiently
      control disease progression and virus transmission due to the emergence of drug
      resistant viral strains. In this study, germacrone, which is a major component of
      the essential oils extracted from Rhizoma Curcuma, was found to inhibit influenza
      virus replication. Germacrone showed antiviral activity against the H1N1 and H3N2
      influenza A viruses and the influenza B virus in a dose-dependent manner. The
      viral protein expression, RNA synthesis and the production of infectious progeny
      viruses were decreased both in MDCK and A549 cells treated with germacrone. In a
      time-of-addition study, germacrone was found to exhibit an inhibitory effect on
      both the attachment/entry step and the early stages of the viral replication
      cycle. Germacrone also exhibited an effective protection of mice from lethal
      infection and reduced the virus titres in the lung. Furthermore, the combination
      of germacrone and oseltamivir exhibited an additive effect on the inhibition of
      influenza virus infection, both in vitro and in vivo. Our results suggest that
      germacrone may have the potential to be developed as a therapeutic agent alone or
      in combination with other agents for the treatment of influenza virus infection. 

PMID- 24095671
TI  - Cardiovascular responses to injections of angiotensin II or carbachol into the
      rostral ventrolateral medulla in rats with AV3V lesions.
AB  - Injection of l-glutamate (GLU) into the rostral ventrolateral medulla (RVLM)
      produces sympathetically-mediated pressor responses that depend on the integrity
      of the tissue surrounding the anteroventral third ventricle (AV3V region). The
      injection of angiotensin II (ANG II) or the cholinergic agonist carbachol into
      the RVLM also produces pressor responses. In the present study, we investigated
      if the lesion of the AV3V region affects the pressor responses to ANG II or
      carbachol injected into the RVLM in unanesthetized rats. Male Holtzman rats with
      sham or electrolytic AV3V lesions and a stainless steel cannula implanted into
      the RVLM were used. The pressor responses to ANG II (200ng/100nl) injected into
      the RVLM were reduced by acute (1 day) (12+/-3 vs. sham lesions: 26+/-4mmHg) or
      chronic (15 days) AV3V lesions (12+/-5 vs. sham lesions: 27+/-4mmHg), whereas
      acute or chronic AV3V lesions did not affect the pressor responses to carbachol
      (1nmol/100nl) injected into the RVLM. The present results suggest that the AV3V
      region modulates the excitability of the RVLM neurons involved with the pressor
      response produced by the activation of angiotensinergic mechanisms in this area. 

PMID- 24095673
TI  - Reactive oxygen species at phospholipid bilayers: distribution, mobility and
      permeation.
AB  - Reactive oxygen species (ROS) are involved in biochemical processes such as redox
      signaling, aging, carcinogenesis and neurodegeneration. Although biomembranes are
      targets for reactive oxygen species attack, little is known about the role of
      their specific interactions. Here, molecular dynamics simulations were employed
      to determine the distribution, mobility and residence times of various reactive
      oxygen species at the membrane-water interface. Simulations showed that molecular
      oxygen (O2) accumulated at the membrane interior. The applicability of this
      result to singlet oxygen ((1)O2) was discussed. Conversely, superoxide (O2(-))
      radicals and hydrogen peroxide (H2O2) remained at the aqueous phase. Both
      hydroxyl (HO) and hydroperoxyl (HO2) radicals were able to penetrate deep into
      the lipid headgroups region. Due to membrane fluidity and disorder, these
      radicals had access to potential peroxidation sites along the lipid hydrocarbon
      chains, without having to overcome the permeation free energy barrier.
      Strikingly, HO2 radicals were an order of magnitude more concentrated in the
      headgroups region than in water, implying a large shift in the acid-base
      equilibrium between HO2 and O2(-). In comparison with O2, both HO and HO2
      radicals had lower lateral mobility at the membrane. Simulations revealed that
      there were intermittent interruptions in the H-bond network around the HO
      radicals at the headgroups region. This effect is expected to be unfavorable for
      the H-transfer mechanism involved in HO diffusion. The implications for lipid
      peroxidation and for the effectiveness of membrane antioxidants were evaluated. 

PMID- 24095672
TI  - Preadolescent drd1-EGFP mice exhibit cocaine-induced behavioral sensitization.
AB  - In adult mice, repeated cocaine administration induces behavioral sensitization
      measured as increased horizontal locomotor activity. Cocaine-induced locomotor
      sensitization has been well characterized in adult mice. In adult animals, the D1
      dopamine receptor is important for mediating effects of cocaine. The effect of
      cocaine on D1 receptor expression and function in preadolescent animals is less
      understood. The recently described drd1-enhanced green fluorescent protein (drd1
      EGFP) reporter mouse is a useful model for performing such mechanistic studies;
      however, preadolescent drd1-EGFP mice have not been characterized previously.
      Here we studied cocaine-induced locomotor sensitization in preadolescent drd1
      EGFP reporter mice. We administered 15mg/kg cocaine three times daily at 1h
      intervals for seven consecutive days beginning on postnatal day 23 to drd1-EGFP
      reporter mice and the commonly used C57BL/6 mice. Under this regimen,
      preadolescent mice of both strains exhibited cocaine-induced locomotor
      sensitization; however, by day 7 the cocaine-induced locomotor activity in the
      drd1-EGFP mice was maintained for a longer duration compared to the C57BL/6 mice.
      The preadolescent drd1-EGFP mice also exhibited elevated basal locomotor activity
      in a novel environment and had higher D1 and D2 dopamine receptor mRNA levels in
      the caudate nucleus compared to the C57BL/6 mice. The cocaine-induced locomotor
      sensitization was not retained when the drd1-EGFP mice were maintained cocaine
      free for two weeks suggesting that in preadolescent drd1-EGFP mice the cocaine
      induced changes do not persist. 

PMID- 24095674
TI  - Budded baculoviruses as a tool for a homogeneous fluorescence anisotropy-based
      assay of ligand binding to G protein-coupled receptors: the case of melanocortin
      4 receptors.
AB  - We present here the implementation of budded baculoviruses that display G protein
      coupled receptors on their surfaces for the investigation of ligand-receptor
      interactions using fluorescence anisotropy (FA). Melanocortin 4 (MC4) receptors
      and the fluorescent ligand Cy3B-NDP-alpha-MSH were used as the model system. The
      real-time monitoring of reactions and the high assay quality allow the
      application of global data analysis with kinetic mechanistic models that take
      into account the effect of nonspecific interactions and the depletion of the
      fluorescent ligand during the reaction. The receptor concentration, affinity and
      kinetic parameters of fluorescent ligand binding as well as state anisotropies
      for different fluorescent ligand populations were determined. At low Cy3B-NDP
      alpha-MSH concentrations, a one-site receptor-ligand binding model described the
      processes, whereas divergence from this model was observed at higher ligand
      concentrations, which indicated a more complex mechanism of interactions similar
      to those mechanisms that have been found in experiments with radioactive ligands.
      The information obtained from our kinetic experiments and the inherent
      flexibility of FA assays also allowed the estimation of binding parameters for
      several MC4 receptor-specific unlabelled compounds. In summary, the FA assay that
      was developed with budded baculoviruses led the experimental data to a level that
      would solve complex models of receptor-ligand interactions also for other
      receptor systems and would become as a valuable tool for the screening of
      pharmacologically active compounds. 

PMID- 24095675
TI  - Assessment of beating parameters in human induced pluripotent stem cells enables
      quantitative in vitro screening for cardiotoxicity.
AB  - Human induced pluripotent stem cell (iPSC)-derived cardiomyocytes show promise
      for screening during early drug development. Here, we tested a hypothesis that in
      vitro assessment of multiple cardiomyocyte physiological parameters enables
      predictive and mechanistically-interpretable evaluation of cardiotoxicity in a
      high-throughput format. Human iPSC-derived cardiomyocytes were exposed for 30 min
      or 24 h to 131 drugs, positive (107) and negative (24) for in vivo
      cardiotoxicity, in up to 6 concentrations (3 nM to 30 uM) in 384-well plates.
      Fast kinetic imaging was used to monitor changes in cardiomyocyte function using
      intracellular Ca(2+) flux readouts synchronous with beating, and cell viability.
      A number of physiological parameters of cardiomyocyte beating, such as beat rate,
      peak shape (amplitude, width, raise, decay, etc.) and regularity were collected
      using automated data analysis. Concentration-response profiles were evaluated
      using logistic modeling to derive a benchmark concentration (BMC) point-of
      departure value, based on one standard deviation departure from the estimated
      baseline in vehicle (0.3% dimethyl sulfoxide)-treated cells. BMC values were used
      for cardiotoxicity classification and ranking of compounds. Beat rate and several
      peak shape parameters were found to be good predictors, while cell viability had
      poor classification accuracy. In addition, we applied the Toxicological
      Prioritization Index (ToxPi) approach to integrate and display data across many
      collected parameters, to derive "cardiosafety" ranking of tested compounds. Multi
      parameter screening of beating profiles allows for cardiotoxicity risk assessment
      and identification of specific patterns defining mechanism-specific effects.
      These data and analysis methods may be used widely for compound screening and
      early safety evaluation in drug development.

PMID- 24095676
TI  - HIF-2alpha protects human hematopoietic stem/progenitors and acute myeloid
      leukemic cells from apoptosis induced by endoplasmic reticulum stress.
AB  - Hematopoietic stem and progenitor cells (HSPCs) are exposed to low levels of
      oxygen in the bone marrow niche, and hypoxia-inducible factors (HIFs) are the
      main regulators of cellular responses to oxygen variation. Recent studies using
      conditional knockout mouse models have unveiled a major role for HIF-1alpha in
      the maintenance of murine HSCs; however, the role of HIF-2alpha is still unclear.
      Here, we show that knockdown of HIF-2alpha, and to a much lesser extent HIF
      1alpha, impedes the long-term repopulating ability of human CD34(+) umbilical
      cord blood cells. HIF-2alpha-deficient HSPCs display increased production of
      reactive oxygen species (ROS), which subsequently stimulates endoplasmic
      reticulum (ER) stress and triggers apoptosis by activation of the unfolded
      protein-response (UPR) pathway. HIF-2alpha deregulation also significantly
      decreased engraftment ability of human acute myeloid leukemia (AML) cells.
      Overall, our data demonstrate a key role for HIF-2alpha in the maintenance of
      human HSPCs and in the survival of primary AML cells. 

PMID- 24095677
TI  - Minimally invasive myomectomy using unidirectional knotless barbed suture.
AB  - STUDY OBJECTIVE: To demonstrate the technique for closure of the uterine wall
      defect during minimally invasive myomectomy using unidirectional knotless barbed
      suture. DESIGN: Step-by-step explanation of the technique using videos and
      pictures (educational video). SETTING: Women have a 70% to 80% lifetime risk of
      developing uterine leiomyomas. Myomectomy is a common procedure performed for
      conservative treatment of leiomyomas that is frequently performed using a
      minimally invasive technique. Knotless barbed sutures have recently been used
      successfully in minimally invasive myomectom procedures. Advantages of using
      barbed sutures in this setting include the ability to perform knotless suturing
      and rapid suture deployment, which may result in decreased operative time and
      blood loss. In addition, the tensile strength of the suture is maintained by the
      barbs, which facilitates the operative procedure and may potentially lead to a
      more even distribution of tension along the closure. INTERVENTIONS: Closure of
      the uterine wall defect using unidirectional knotless barbed suture during
      minimally invasive myomectomy. CONCLUSION: The use of unidirectional knotless
      barbed suture substantially facilitates closure of uterine defects during
      minimally invasive myomectomy and may offer additional advantages such as
      minimizing operative time.

PMID- 24095678
TI  - Underage drinking in the UK: changing trends, impact and interventions. A rapid
      evidence synthesis.
AB  - The UK is a high prevalence country for underage alcohol use. We conducted an
      evidence synthesis to examine (1) the changing trends in underage drinking in the
      UK compared to Europe and the USA, (2) the impact of underage drinking in terms
      of hospital admissions, (3) the association between underage drinking and violent
      youth offending, and (4) the evidence base for the effectiveness of alcohol harm
      reduction interventions aimed at children and adolescents under the age of 18
      years. The following databases were searched from November 2002 until November
      2012: Cochrane Database of Systematic Reviews, National Institute for Health and
      Clinical Excellence, The Evidence for Policy and Practice Information, DARE,
      Medline, The Campbell Collaboration, CINAHL, Criminal Justice Abstracts, Psych
      INFO and Social Care Online. Our findings revealed changes in the way children
      drink in the UK and how much they drink. Alcohol related harms are increasing in
      the UK despite overall population levels of consumption reducing in this age
      group. Girls aged 15-16 years report binge drinking and drunkenness more than
      boys. Girls are also more likely than boys to be admitted to hospital for alcohol
      related harm. The evidence suggests a strong association between heavy episodic
      binge drinking and violent youth offending. Only 7 out of 45 randomised
      controlled trials (RCTs) identified for this review included children and
      adolescents under the age of 18 years. Most were delivered in the emergency
      department (ED) and involved a brief intervention. All were characterised by a
      wide age range of participants, heterogeneous samples and high rates of refusal
      and attrition. The authors conclude that whilst the ED might be the best place to
      identify children and adolescents at risk of harm related to alcohol use it might
      not be the best place to deliver an intervention. Issues related to a lack of
      engagement with alcohol harm reduction interventions have been previously
      overlooked and warrant further investigation. 

PMID- 24095679
TI  - From political controversy to a technical problem? Fifteen years of opioid
      substitution treatment in Finland.
AB  - BACKGROUND: The aim of the article is to analyze changes in opioid substitution
      treatments (OST) in Finland. OST spread in Finland in the late 1990s and early
      2000s (Phase 1). Since then, OST has become an integrated part of Finnish drug
      policy and is provided in various substance abuse treatment units as well as in
      municipal health centers (Phase 2). METHODS: The paper analyses the policy around
      the implementation of opioid substitution treatment in Finland, focusing on
      identifying the key factors and the relations between them that have contributed
      to the implementation of OST in Finland. RESULTS: OST has become accepted in
      Finland during the past ten years as a crucial element of a harm reduction
      strategy. Present incentives behind this development are not as clearly related
      to drug-specific policies as in the late 1990s; rather, they stem from both the
      restructuring of health care services (e.g. cost-effectiveness) and the
      strengthening of the medical or technico-administrative approach to the
      development of OST. CONCLUSION: Since the early 2000s, the development of
      substitution treatment in Finland has not taken place under explicit drug
      political guidance, but largely as a result of many differing intended and
      unintended effects. One of the unintended effects is the fact that buprenorphine
      has replaced heroin as the most commonly misused opioid in Finland.

PMID- 24095680
TI  - Predicting the length of hospital stay of psychiatry patients using signal
      detection analysis.
AB  - In Japan, the length of hospital stay (LOS) at psychiatric institutions often
      exceeds a year, and factors related to such stays have been identified. However,
      we do not know how multiple patient, hospital, and physician factors interact to
      determine LOS. Patient data were collected from a psychiatric hospital in Osaka,
      Japan. We developed subgroups, which were determined by interactions related to
      LOS using signal detection theory. In acute or emergency wards, five factors
      related to LOS were identified, and subjects were categorized into six subgroups.
      The indices obtained by the five factors ranged 2.49-3.47 for odds ratio, 0.47
      0.84 for sensitivity, 0.40-0.76 for specificity, and 0.52-0.71 for positive
      predictive value. In general wards, five factors related to LOS were identified,
      and subjects were categorized into six subgroups. The indices obtained by the
      five factors ranged 3.02-5.36 for odds ratio, 0.58-0.86 for sensitivity, 0.37
      0.68 for specificity, and 0.85-0.92 for positive predictive value. Psychiatrists
      who have been practicing longer in acute or emergency wards appear to have
      significantly longer stay of patients, and older or more severe patients tend to
      be in need of longer inpatient care. Our results provide findings that may be
      helpful in decreasing LOS at psychiatric hospitals. 

PMID- 24095681
TI  - Looking for protein expression signatures in European eel peripheral blood
      mononuclear cells after in vivo exposure to perfluorooctane sulfonate and a real
      world field study.
AB  - The decline of European eel population can be attributed to many factors such as
      pollution by xenobiotics present in domestic and industrial effluents.
      Perfluorooctane sulfonate (PFOS) is a ubiquitous compound of a particular concern
      in Europe. PFOS can reach high concentrations in tissues of organisms and many
      toxic effects have been reported in fish. This study aimed at evaluating the
      toxicological effects of PFOS in European eel peripheral blood mononuclear cells
      (PBMCs) at the protein expression level. To identify proteins whose expression
      was modified by PFOS, we performed a proteomic analysis on the post-nuclear
      fraction of PBMCs after a chronic exposure (28 days) of yellow eels to zero, 1 or
      10 MUg/L PFOS. This in vivo study was completed by a proteomic field study on
      eels sampled in Belgian rivers presenting different PFOS pollution degrees.
      Proteins were separated by two-dimensional in-gel electrophoresis (2D-DIGE) to
      compare the post-nuclear fraction of PBMCs from the reference group with cells
      from fish exposed to the pollutant of interest. On the 28 spots that were
      significantly (p < 0.05; ANOVA followed by a Dunnett post-hoc test) affected by
      PFOS in the in vivo experiment, a total of 17 different proteins were identified
      using nano-LC ESI-MS/MS and the Peptide and Protein Prophet of Scaffold software.
      In the field experiment, 18 significantly (p < 0.05; ANOVA followed by Dunnett's
      test) affected spots conducted to the identification of 16 different proteins.
      Interestingly, only three proteins were found in common between in vivo and in
      situ experiments: plastin-2, alpha-enolase and glyceraldehyde 3-phosphate
      dehydrogenase. Comparing the results with a previous study, plastin-2 and alpha
      enolase were also been found to be affected after in vitro exposure of PBMCs
      during 48 h to either 10 MUg or 1 mg PFOS/L. Potential use of these proteins as
      biomarkers of PFOS exposure in European eel could indicate early warning signals.

PMID- 24095682
TI  - ApicoAMP: the first computational model for identifying apicoplast-targeted
      transmembrane proteins in Apicomplexa.
AB  - BACKGROUND: Computational identification of apicoplast-targeted proteins is
      important in drug target determination for diseases such as malaria. While there
      are established methods for identifying proteins with a bipartite signal in
      multiple species of Apicomplexa, not all apicoplast-targeted proteins possess
      this bipartite signature. The publication of recent experimental findings of
      apicoplast membrane proteins, called transmembrane proteins, that do not possess
      a bipartite signal has made it feasible to devise a machine learning approach for
      identifying this new class of apicoplast-targeted proteins computationally.
      METHODOLOGY/PRINCIPAL FINDINGS: In this work, we develop a method for predicting
      apicoplast-targeted transmembrane proteins for multiple species of Apicomplexa,
      whereby several classifiers trained on different feature sets and based on
      different algorithms are evaluated and combined in an ensemble classification
      model to obtain the best expected performance. The feature sets considered are
      the hydrophobicity and composition characteristics of amino acids over
      transmembrane domains, the existence of short sequence motifs over cytosolically
      disposed regions, and Gene Ontology (GO) terms associated with given proteins.
      Our model, ApicoAMP, is an ensemble classification model that combines decisions
      of classifiers following the majority vote principle. ApicoAMP is trained on a
      set of proteins from 11 apicomplexan species and achieves 91% overall expected
      accuracy. CONCLUSIONS/SIGNIFICANCE: ApicoAMP is the first computational model
      capable of identifying apicoplast-targeted transmembrane proteins in Apicomplexa.
      The ApicoAMP prediction software is available at
      http://code.google.com/p/apicoamp/ and http://bcb.eecs.wsu.edu.

PMID- 24095684
TI  - Influence of the Ca(2+) ion on the Mn4Ca conformation and the H-bond network
      arrangement in Photosystem II.
AB  - In the crystal structure of Photosystem II (PSII) analyzed at a resolution of
      1.9A, most of the bond lengths between Mn and O atoms in the oxygen-evolving
      Mn4Ca cluster are 1.8-2.1A. On the other hand, the Mn1O5 bond in the Mn3CaO4
      cubane region of the Mn4Ca cluster is significantly elongated to 2.6A. Using a
      quantum mechanical/molecular mechanical approach, we investigated factors that
      are responsible for distortion of the Mn3CaO4 cubane. Removal of Ca led to
      shortening the Mn1O5 bond by 0.2A; however, Mn1O5 remained significantly
      elongated, at >2.5A. Conversely, removal of Mn4 significantly shortens the Mn1O5
      distance by 0.5A to 2.2A, resulting in a more symmetric cubane shape. These
      results suggest that Mn4, not Ca, is predominantly responsible for distortion of
      the Mn3CaO4 cubane. It was not the Ca component that was responsible for the
      existence of the two S2 conformers but two different Mn oxidation states (Mn1,
      Mn2, Mn3, M4)=(III, IV, IV, IV) and (IV, IV, IV, III); they were interconvertible
      by translocation of the O5 atom along the Mn1-O5-Mn4 axis. Depletion of Ca
      resulted in rearrangement of the H-bond network near TyrZ, which proceeds via a
      chloride ion (Cl-1 pathway). This may explain why Ca depletion inhibits the S2 to
      S3 transition, the same process that can also be inhibited by Cl(-) depletion. 

PMID- 24095685
TI  - Structural changes in rod outer segments of frog and mouse after illumination.
AB  - Intact eyes of frog and mouse were studied by X-ray diffraction. Light-induced
      changes in the reflections from the rod outer segments (ROS) were recorded at a
      time resolution of 0.1 and 1 s in frog and mouse, respectively. Lamellar
      diffraction from disk membranes was observed to the 10th order. In frog, the
      intensities of seven reflections were found to change significantly on 7-s
      intense illumination and the lamellar spacing, which was 30.4 nm in darkness,
      decreased by 0.5%. Time courses of changes in the intensity and the lamellar
      spacing were similar, saturating at about 7 s. Most of the intensity changes
      could be attributable to the spacing change. Thus, the effect of light on the
      electron density distribution was smaller than previously reported. The decrease
      in the lamellar spacing is attributed to changes in the intracellular ionic
      concentrations due to the blockage of the dark current. This may be a useful
      index to study the ionic movements in the cell. Mouse ROS's had a lamellar
      spacing larger than frog (32.4 nm). The structural changes after illumination
      were similar to those in frog ROS. This X-ray diffraction technique may be
      utilized to study functions of photoreceptor cells in transgenic mice and other
      animals. 

PMID- 24095683
TI  - Neural mechanisms of pain and alcohol dependence.
AB  - An association between chronic pain conditions and alcohol dependence has been
      revealed in numerous studies with episodes of alcohol abuse antedating chronic
      pain in some people and alcohol dependence emerging after the onset of chronic
      pain in others. Alcohol dependence and chronic pain share common neural circuits
      giving rise to the possibility that chronic pain states could significantly
      affect alcohol use patterns and that alcohol dependence could influence pain
      sensitivity. The reward and emotional pathways that regulate drug/alcohol
      addiction also mediate chronic pain. For example, pain-evoked activation of brain
      learning and brain reward circuitry may modulate cortical processing of pain and
      central sensitization mediated by mesocorticolimbic circuitry. Imbalance and
      reorganization of amygdala-mPFC interactions may not only be important for
      persistent pain, but also for disorders characterized by the abnormal persistence
      of emotional-affective states such as drug and alcohol addiction. Further studies
      are necessary to understand how these neural circuits are regulated in comorbid
      conditions of alcoholism and chronic pain. In addition, long term alcohol use
      could induce pain symptoms and may exacerbate chronic pain arising from other
      sources. While prior studies have established a role of neuroendocrine stress
      axis mediators in alcohol abuse and neurotoxic effects, these studies have not
      explored the distinction between the individual impact of alcohol and stress
      hormones. Future studies should explore the mechanisms mediating the contribution
      of alcohol and stress axis hormones on pain, an important question in our
      understanding of the neurobiology of alcohol abuse and chronic pain. 

PMID- 24095686
TI  - Effect of onabotulinumtoxinA treatment on symptoms and urodynamic findings in
      pediatric neurogenic bladder.
AB  - OBJECTIVE: To evaluate clinical and urodynamic efficiency of onabotulinumtoxinA
      (Botox) treatment in pediatric patients with urinary incontinence due to
      neurogenic overactive bladder. PATIENTS AND METHODS: Seventeen patients aged from
      6 to 17 years (median 11 years) were treated with Botox injections. Clinical
      response to incontinence, duration of the response, and urodynamic results before
      and 1-3 months after treatment were evaluated. RESULTS: Mean incontinence
      frequency decreased significantly (p = 0.036); six of 17 patients had >90%
      reduction, and a further three patients had a 50-90% reduction in incontinence
      episodes. Median duration of the response was 15 months (range 3-42 months). Mean
      bladder volume changed from 380 +/- 148 ml to 453 +/- 147 (p = 0.078), maximal
      detrusor pressure decreased from 45 +/- 31 cmH2O to 32 +/- 21 cmH2O (p = 0.030),
      and the number of patients with detrusor contractions during filling decreased
      from 12 to three (p = 0.005) after the treatment. The patients with poor bladder
      compliance had either no response or a short duration of response. At follow-up
      eight patients had undergone bladder augmentation because of persistent
      incontinence. CONCLUSIONS: About one third of pediatric patients with neurogenic
      bladder had a good response to Botox treatment. In many patients, the clinical
      response was longer than expected. The patients who initially had poor bladder
      compliance had a poor response to the treatment.

PMID- 24095687
TI  - High incidence of urinary stones in Uyghur children may be related to local
      environmental factors.
AB  - OBJECTIVE: To analyze the causes of urolithiasis in Uyghur children from
      Xinjiang. PATIENTS AND METHODS: We retrospectively evaluated the clinical
      features and characteristics of urinary stone composition of 220 Uyghur pediatric
      patients with urolithiasis between March 2009 and June 2011. The data were
      compared with that of 100 Uyghur children without urolithiasis who visited the
      Child Care Clinic for regular health check-ups. The stones were collected by
      endoscopy or open surgery, and analyzed using infrared spectroscopy. RESULTS: The
      mean age of the 220 Uyghur children was 7.48 +/- 4.73 years (range, 0.8-17.0
      years). The overall sex ratio (male:female) was 2.23:1. The predominant pure
      stone was ammonium urate (58.9%), whereas the predominant mixed stone was calcium
      oxalate mixture (91.1%). Uric acid stones comprised 54% of all stones. Urinary
      tract infections were observed in 42.3% and 4.0% of the patient and control
      groups, respectively. The mean urinary pH values were 5.77 +/- 0.67 and 6.42 +/-
      0.67, respectively (p < 0.001). pH values were <5.5 in 52.7% and 6% of the
      patient and control groups, respectively. On 24-h urine analysis, we found
      metabolic disturbances in these patients: hypercalciuria in 6.8% cases,
      hyperphosphaturia in 16.8% cases, hyperuricosuria in 21.4% cases, and
      hypomagnesiuria in 34.1% cases. CONCLUSIONS: Urolithiasis in Uyghur children may
      be primarily related to local environmental factors.

PMID- 24095688
TI  - Early clean intermittent catheterization may not prevent dimercaptosuccinic acid
      renal scan abnormalities in children with spinal dysraphism.
AB  - OBJECTIVES: To determine whether early initiation of clean intermittent
      catheterization is associated with increased renal preservation in children with
      spinal dysraphism based on dimercaptosuccinic acid (DMSA) renal scans. METHODS: A
      retrospective review was performed of 100 patients from a pediatric spinal
      defects clinic from June 2007 to October 2011 who were followed with routine
      studies including DMSA scans, voiding cystourethrograms, renal/bladder
      ultrasounds, and urodynamics. DMSA scans were reviewed for evidence of renal
      cortical loss as defined by presence of scarring or difference in differential
      function greater than 15%. Multivariate analysis was performed for risk factors
      for upper tract damage. RESULTS: Renal cortical loss on DMSA scan was found in
      43/100 (43%) of patients. CIC was started at birth in 17/100 (17%) of patients
      with the rest starting at a median age of 5 years (IQR 3-9). Upon multivariate
      regression analysis, age at DMSA scan (OR 1.21; 95% CI 1.08-1.36), history of VUR
      (OR 8.64; 95% CI 2.52-29.57), history of hydronephrosis (OR 3.44; 95% CI 1.12
      10.5), and CIC from birth (OR 9.26; 95% CI 1.99-43.18) were statistically
      significant predictors of kidney damage. CONCLUSION: Early initiation of CIC may
      not reduce the incidence of DMSA abnormalities in pediatric patients with spinal
      dysraphism.

PMID- 24095689
TI  - Fine tuning the LightOn light-switchable transgene expression system.
AB  - Spatiotemporal control of transgene expression in living cells provides new
      opportunities for the characterization of gene function in complex biological
      processes. We previously reported a synthetic, light-switchable transgene
      expression system called LightOn that can be used to control gene expression
      using blue light. In the present study, we modified the different promoter
      segments of the light switchable transcription factor GAVPO and the target gene,
      and assayed their effects on protein expression under dark or light conditions.
      The results showed that the LightOn system maintained its high on/off ratio under
      most modifications, but its induction efficiency and background gene expression
      level can be fine-tuned by modifying the core promoter, the UASG sequence number,
      the length of the spacer between UASG and the core promoter of the target
      protein, and the expression level of the GAVPO transcription factor. Thus, the
      LightOn gene expression system can be adapted to a large range of applications
      according to the requirements of the background and the induced gene expression. 

PMID- 24095690
TI  - Prediction of regulation relationship between protein interactions in signaling
      networks.
AB  - The discovery of regulation relationship of protein interactions is crucial for
      the mechanism research in signaling network. Bioinformatics methods can be used
      to accelerate the discovery of regulation relationship between protein
      interactions, to distinguish the activation relations from inhibition relations.
      In this paper, we describe a novel method to predict the regulation relations of
      protein interactions in the signaling network. We detected 4,417 domain pairs
      that were significantly enriched in the activation or inhibition dataset. Three
      machine learning methods, logistic regression, support vector machines(SVMs), and
      naive bayes, were explored in the classifier models. The prediction power of
      three different models was evaluated by 5-fold cross-validation and the
      independent test dataset. The area under the receiver operating characteristic
      curve for logistic regression, SVM, and naive bayes models was 0.946, 0.905 and
      0.809, respectively. Finally, the logistic regression classifier was applied to
      the human proteome-wide interaction dataset, and 2,591 interactions were
      predicted with their regulation relations, with 2,048 in activation and 543 in
      inhibition. This model based on domains can be used to identify the regulation
      relations between protein interactions and furthermore reconstruct signaling
      pathways. 

PMID- 24095691
TI  - Laparoscopic sleeve gastrectomy for a two-and half year old morbidly obese child.
AB  - INTRODUCTION: Laparoscopic sleeve gastrectomy (LSG) is an accepted technique in
      bariatric surgery for reducing obesity. Recent reports indicate it to be
      effective even in children but it has not been tried in very young children.
      PRESENTATION OF CASE: We report here a case of a 2 and half years old child
      subjected to LSG for his morbid obesity and associated obstructive sleep apnea
      and bowing of legs. LSG was performed after investigations ruled out hereditary
      or genetic causes of obesity. The procedure was well tolerated without any
      complications and 2 months post surgery, the obstructive sleep apnea decreased
      substantially. The child was followed up for two years. At the last follow up BMI
      was drastically reduced from a pre surgical value of 41.1-24kg/m(2) at 24 months
      post surgery. DISCUSSION: Prior to our report the youngest child to undergo
      sleeve gastrectomy was 5 years old from Saudi Arabia. We observed LSG to be safe
      and effective in reducing obesity and related co morbidities in a two and half
      year's old child. CONCLUSION: The results suggest that LSG can be a safe and
      effective alternative for weight control in morbidly obese children even of less
      than 3 years of age. However more studies and long term follow up is essential
      for monitoring the growth and development of children subjected to LSG.

PMID- 24095692
TI  - Localized infusions of the partial alpha 7 nicotinic receptor agonist SSR180711
      evoke rapid and transient increases in prefrontal glutamate release.
AB  - The ability of local infusions of the alpha 7 nicotinic acetycholine receptor
      (alpha7 nAChR) partial agonist SSR180711 to evoke glutamate release in prefrontal
      cortex was determined in awake rats using a microelectrode array. Infusions of
      SSR180711 produced dose-dependent increases in glutamate levels. The lower dose
      (1.0MUg in 0.4MUL) evoked a rapid rise (~1.0s) in glutamate (1.41+/-0.30MUM above
      baseline). The higher dose (5.0MUg) produced a similarly rapid, yet larger
      increase (3.51+/-0.36MUM above baseline). After each dose, the glutamate signal
      was cleared to basal levels within 7-18s. SSR180711-evoked glutamate was mediated
      by the alpha7 nAChR as co-infusion of the selective alpha7 nAChR antagonist alpha
      bungarotoxin (10.0MUM)+SSR1808711 (5.0MUg) reduced the effect of 5.0MUg alone by
      87% (2.62 vs. 0.35MUM). Finally, the clearance of the SSR180711 (5.0MUg)-evoked
      glutamate was bidirectionally affected by drugs that inhibited (threo-beta-benzyl
      oxy-aspartate (TbetaOA), 100.0MUM) or facilitated (ceftriaxalone, 200mg/kg, i.p.)
      excitatory amino acid transporters. TbetaOA slowed both the clearance (s) and
      rate of clearance (MUM/s) by 10-fold, particularly at the mid-late stages of the
      return to baseline. Ceftriaxone reduced the magnitude of the SSR180711-evoked
      increase by 65%. These results demonstrate that pharmacological stimulation of
      alpha7 nAChRs within the prefrontal cortex is sufficient to evoke rapid yet
      transient increases in glutamate levels. Such increases may underlie the
      cognition-enhancing effects of the drug in animals; further justifying studies on
      the use of alpha7 nAChR-positive modulators in treating cognition-impairing
      disorders in humans. 

PMID- 24095694
TI  - Quercetin suppress microglial neuroinflammatory response and induce
      antidepressent-like effect in olfactory bulbectomized rats.
AB  - In rodents, olfactory bulbectomy (OBX) results in several behavioral and
      biochemical changes, useful as a screening model for antidepressants. Recent
      evidences suggest that quercetin; a bioflavonoid exhibits a variety of behavioral
      effects including anxiolytic, antidepressant, etc. Since microglia are commonly
      implicated in the neuroinflammation cascade of depression, we hypothesized that
      quercetin might involve microglial inhibition pathway in its antidepressant-like
      effects. To support such a possibility, we investigated the interaction of
      quercetin with a known microglial inhibitor (minocycline) against OBX-induced
      depression in male Wistar rats. In our study, ablation of olfactory bulbs caused
      hyperactivity in open field arena and increased immobility time in forced swim
      test (FST) which was coupled with enhanced serum corticosterone levels.
      Additionally, there were increased oxidative-nitrosative stress markers,
      inflammatory mediators (tumor necrosis factor-alpha (TNF-alpha) and interleukin-6
      (IL-6)) along with enhanced apoptotic factor (caspase-3) in both cerebral cortex
      and hippocampal brain regions of OBX animals. These results were further
      supported by reports from histopathological analysis. After a surgical recovery
      period of 2weeks, treatment with quercetin (40, 80mg/kg; per oral (p.o.) p.o.,
      14days) significantly prevented OBX-induced behavioral, biochemical, molecular
      and histopathological alterations. Further, combination of sub effective doses of
      quercetin (20, 40mg/kg; p.o.) with minocycline (25mg/kg; p.o.) significantly
      potentiated their protective effects as compared to their effects alone. Based on
      our results, we propose that microglial inhibitory pathway might be involved in
      the neuroprotective effects of quercetin and suppression of oxidative-nitrosative
      stress mediated neuroinflammation-apoptotic cascade associated with OBX rat model
      of depression. 

PMID- 24095693
TI  - The p75NTR signaling cascade mediates mechanical hyperalgesia induced by nerve
      growth factor injected into the rat hind paw.
AB  - Nerve growth factor (NGF) augments the excitability of isolated rat sensory
      neurons through activation of the p75 neurotrophin receptor (p75(NTR)) and its
      downstream sphingomyelin signaling cascade, wherein neutral sphingomyelinase(s)
      (nSMase), ceramide, and the atypical protein-kinase C (aPKC), protein-kinase M
      zeta (PKMzeta), are key mediators. Here we examined these same receptor-pathways
      in vivo for their role in mechanical hyperalgesia from exogenous NGF. Mechanical
      sensitivity was tested by the number of paw withdrawals in response to 10 stimuli
      (PWF=n/10) by a 4-g von Frey hair (VFH, testing "allodynia") and by 10 and 15g
      VFHs (testing "hyperalgesia"). NGF (500ng/10MUL) injected into the male rat's
      plantar hind paw induced long-lasting ipsilateral mechanical hypersensitivity.
      Mechano-hypersensitivity, relative to baseline responses and to those of the
      contralateral paw, developed by 0.5-1.5h and remained elevated at least for 21
      24h, Acute intraplantar pre-treatment with nSMase inhibitors, glutathione (GSH)
      or GW4869, prevented the acute hyperalgesia from NGF (at 1.5h) but not that at
      24h. A single injection of N-acetyl sphingosine (C2-ceramide), simulating the
      ceramide produced by nSMase activity, induced ipsilateral allodynia that
      persisted for 24h, and transient hyperalgesia that resolved by 2h. Intraplantar
      injection of hydrolysis-resistant mPro-NGF, selective for the p75(NTR) over the
      tyrosine kinase (TrkA) receptor, gave very similar results to NGF and was
      susceptible to the same inhibitors. Hyperalgesia from both NGF and mPro-NGF was
      prevented by paw pre-injection with blocking antibodies to rat p75(NTR) receptor.
      Finally, intraplantar (1day before NGF) injection of mPSI, the myristolated
      pseudosubstrate inhibitor of PKCzeta/PKMzeta, decreased the hyperalgesia
      resulting from NGF or C2-ceramide, although scrambled mPSI was ineffective. The
      findings indicate that mechano-hypersensitivity from peripheral NGF involves the
      sphingomyelin signaling cascade activated via p75(NTR), and that a peripheral
      aPKC is essential for this sensitization. 

PMID- 24095695
TI  - Links between L-glutamate transporters, Na+/K+-ATPase and cytoskeleton in
      astrocytes: evidence following inhibition with rottlerin.
AB  - Astrocytes are plastic cells that play key roles in brain physiology and
      pathology, including via their glutamate transporters, excitatory amino acid
      transporter (EAAT)1 and EAAT2, maintaining low extracellular glutamate
      concentrations and protecting against excitotoxic neuronal injury. Alterations in
      cell surface expression of EAATs and astrocytic cytoskeleton are important for
      regulating transporter activity. This study employed the actions of rottlerin, to
      interrogate the regulation of EAAT activity, expression and localization, and
      interfaces with Na(+)/K(+)-ATPase and astrocytic morphology. EAAT activity and
      expression were determined in primary cultures of mouse astrocytes in the
      presence of and after rottlerin removal, with or without trafficking inhibitors,
      using uptake ([(3)H]d-aspartate, (86)Rb(+)) and molecular analyses. Astrocytic
      morphology and EAAT localization were investigated using Western blotting and
      immunocytochemistry, in concert with image analysis of glial fibrillary acidic
      protein, F-actin and EAAT1/2. Rottlerin induced a time-dependent inhibition of
      glutamate transport (Vmax). Rapid changes in cytoskeletal arrangement were
      observed and immunoblotting revealed increases in EAAT2 total and cell surface
      expression, despite reduced EAAT activity. Rottlerin-induced inhibition was
      reversible and its rate was increased by monensin co-treatment. Rottlerin
      inhibited, while monensin stimulated Na(+)/K(+)-ATPase. Removal of rottlerin
      rapidly elevated Na(+)/K(+)-ATPase activity beyond control levels, while co
      treatment with monensin failed to stimulate the Na(+)/K(+)-ATPase. These data
      reveal inhibition of EAAT activity by rottlerin is not associated with loss of
      EAATs at the cell surface, but rather linked to cytoskeletal rearrangement, and
      inhibition of the Na(+)/K(+)-ATPase. Rapid recovery of Na(+)/K(+)-ATPase
      activity, and subsequent restoration of glutamate uptake indicates that
      astrocytic morphology and EAAT activity are co-regulated by a tightly coupled,
      homeostatic relationship between l-glutamate uptake, the electrochemical gradient
      and the activity of the Na(+)/K(+)-ATPase. 

PMID- 24095696
TI  - Nitric oxide, a protective molecule in the cardiovascular system.
AB  - Nitric oxide (NO) is an intra- and inter-signaling molecule that regulates vessel
      dilatation, neuronal transmission, cardiac contraction, immunomodulation, and
      stem cell differentiation and proliferation. NO plays an important protective
      role in the cardiovascular system. NO inhibits smooth muscle cells proliferation
      and migration; enhances proliferation and migration of endothelial cell and
      inhibits apoptosis; suppresses platelet aggregation; and prevents platelet,
      leukocyte and monocyte adhesion to endothelium. NO exerts an inhibitory effect on
      the development of intimal hyperplasia in mechanically or immunologically injured
      vessel. New therapeutic approaches aimed at enhancing NO bioavailability or
      assisting delivery of NO locally may help patients with cardiovascular disease. 

PMID- 24095698
TI  - An ethnobotanical survey of medicinal plants used in Rwanda for voluntary
      depigmentation.
AB  - ETHNOPHARMACOLOGICAL RELEVANCE: Voluntary depigmentation, a very common practice
      in sub-Saharan Africa, often performed with pharmaceutical products diverted from
      their pharmacological use, may cause severe dermatological and systemic side
      effects. The present work aims at investigating whether and which herbs were used
      in Rwanda for similar purposes before the advent of the current depigmentation
      craze; this may give clues at herbal treatments possibly advantageous compared to
      current products. MATERIAL AND METHODS: Sixty-one traditional healers, mostly
      representatives of their associations, were surveyed by questionnaires for
      knowledge and practice of voluntary depigmentation. Recipes or plants used, plant
      parts, harvest area, preparation methods, dosage and route of administration were
      recorded. Most of the cited herbs were harvested with the help of traditional
      healers and identified by comparison with voucher specimens; herbal vouchers of
      the five most cited herbs were deposited in official herbaria. RESULTS: All
      surveyed traditional healers have knowledge of voluntary depigmentation; the
      population currently practicing do not recourse to their services but obtain
      bleaching products directly from the market. Traditional healers disclosed
      recipes prescribed or self-used (often by women) in their youth; others cited
      recipes are used to treat skin diseases with properties of "clarification",
      "black skin stain removal", in cases of hyperpigmentation, and/or "skin
      softening". Curiously, from the 28 recipes cited by traditional healers, all are
      mono-herbal preparations; most of the plants are mixed with butter for
      application to the skin. CONCLUSION: Compared to other pathophysiological
      conditions, there is currently a very limited use of herbal preparations for
      depigmentation. Five herbs had a citation percentage equal or above to 50%,
      Brillantaisia cicatricosa Lindau (Acanthaceae), Chenopodium ugandae (Aellen)
      Aellen (Chenopodiaceae), Dolichopentas longiflora Oliv. (Rubiaceae), Protea
      madiensis Oliv. (Proteaceae) and Sesamum angolense Welw. (Pedaliaceae); in vitro
      experiments indicated a modulation of melanogenesis by these plant extracts,
      confirming the information obtained from traditional healers.

PMID- 24095697
TI  - Evaluation of cholesterol absorption and biosynthesis by decoctions of Annona
      cherimola leaves.
AB  - ETHNOPHARMACOLOGICAL RELEVANCE: Decoctions of the leaves of Annona cherimola
      Mill. are traditionally used in Azores to treat hypercholesterolemia. Although
      they are sold and consumed by people in order to improve their health, these are
      products that cannot be sold with claims for health benefits as they have never
      been studied scientifically. MATERIALS AND METHODS: The activities of decoctions
      from Annona cherimola leaves were analysed for the two therapeutic approaches
      currently used to reduce plasma cholesterol: inhibition of dietary cholesterol
      uptake and inhibition of HMG-CoA reductase activity. Furthermore, the composition
      of the decoction was elucidated by LC-MS and the permeability of the active
      components was analysed using Caco-2 cell monolayers as a model of the intestinal
      barrier (dietary cholesterol uptake). RESULTS: The chemical composition of the
      Annona cherimola leaves' extract revealed that rutin was its main component. The
      in vitro gastrointestinal digestion did not modify the chemical composition of
      the extract. This extract was able to originate a slight reduction in cholesterol
      absorption through Caco-2 cells lines and to reduce the HMG-CoA reductase
      activity in 50% when using 137.3 MUg of the extract/mL. Rutin, when used in the
      same concentration as that found in the extract, was able to reduce cholesterol
      absorption through Caco-2 cells monolayer in approximately 47%. This flavonoid
      had an IC50 of 17.85 MUM relatively to the HMG-CoA reductase activity.
      CONCLUSIONS: The traditional use of decoctions from the leaves of Annona
      cherimola may be justified, at least by the inhibition of HMG-CoA reductase
      activity.

PMID- 24095699
TI  - Traditional medicinal plants in Nigeria--remedies or risks.
AB  - ETHNO-PHARMACOLOGICAL RELEVANCE: Soil pollution due to increasing
      industrialization is a reality that is taking its toll on mankind today.
      Considering the population of people that use herbal remedies especially in
      developing countries and the discharge of industrial waste on surrounding herbal
      vegetation, it is imperative to determine the heavy metals contamination in some
      commonly used medicinal plants. MATERIALS AND METHODS: Representative samples of
      five medicinal plants Ageratum conyzoides, Aspilia africana, Alchornea
      cordifolia, Amaranthus brasiliensis and Chromolaena odorata were collected from
      Ikpoba-Okha L.G.A, Edo State Nigeria, around a paint company and another set of
      same plants were collected from a non-polluted source. Dried leaves and roots of
      collected plants were digested and analyzed using Atomic Absorption
      Spectrophotometer (AAS) for the presence of Lead (Pb), Cadmium (Cd), Chromium
      (Cr), Nickel (Ni) and Zinc (Zn). Soil samples from polluted and non-polluted
      areas were also analyzed to ascertain the levels of these heavy metals in the
      environment. RESULTS: Results show that the concentrations of these heavy metals
      in the leaves and roots of plants collected from polluted soil were significantly
      higher than those obtained from unpolluted soil. Correspondingly heavy metal
      concentrations were significantly higher in polluted than in unpolluted soil
      samples. CONCLUSION: As part of continuing effort in the standardization of
      traditional remedies, environmental contamination control and abatement is
      evident. The source of medicinal plants/herbs should also be a cause for concern
      since the toxicity of medicinal plants is sometimes associated with environmental
      sources of the plants.

PMID- 24095700
TI  - A simple high-performance liquid chromatographic method for the determination of
      brazilin and its application to a pharmacokinetic study in rats.
AB  - ETHNOPHARMACOLOGICAL RELEVANCE: Caesalpinia sappan is a medicinal plant native to
      China popularly used to treat chronic pelvic inflammation, dysmenorrhea and
      hysteromyoma. Its main bioactive component is brazilin which had presented
      antibacterial, anti-inflammatory and anti-platelet aggregation activities. To
      establish a sensitive, selective, reproducible, and accurate high performance
      liquid chromatographic (HPLC) method for the quantitative determination of
      brazilin in plasma, and study the pharmacokinetics of brazilin in rats after
      intravenous administration of brazilin. MATERIALS AND METHODS: Rats received
      intravenous injection of 25, 50 and 100mg/kg of brazilin. Concentrations of
      brazilin in plasma were determined by HPLC method at different time points and
      all pharmacokinetic parameters were estimated by non-compartmental analysis with
      WinNonLin 6.2 software. RESULTS: After single intravenous doses of 25, 50 and
      100mg/kg brazilin in rats, the main PK parameters were as follows: Cmax were 18.1
      +/- 4.1, 46.7 +/- 8.7 and 82.2 +/- 9.6 ug/mL; AUC0-24 were 20.4 +/- 4.3, 48.7 +/-
      6.8 and 90.4 +/- 10.3 ugh/mL; and t1/2 were 5.4 +/- 1.5, 5.8 +/- 0.9 and 6.2 +/-
      1.2h, respectively. CONCLUSION: It showed that the brazilin was eliminated
      moderately in rat by intravenous injection route with t1/2 of 6h and showed a
      dose-dependence profile of Cmax and AUC0-24 at the doses of 25~100mg/kg of
      brazilin for injection in rats.

PMID- 24095701
TI  - The National Birth Defects Prevention Study: how to communicate data.
AB  - The National Birth Defects Prevention Study is a population-based case-control
      study. The study has actively sought to identify children with any of 34
      specified types of malformation. The mothers of affected and unaffected children
      have been interviewed with regard to demographic information, lifestyle factors,
      and exposures. A large number of published studies have appeared and continue to
      appear on diverse exposures and outcomes. An example of such a study identified
      an increased odds ratio for ondansetron use among the mothers of children with
      cleft palate. Possible explanations for associations between exposures and
      outcomes are chance, error, and causation. The ondansetron-cleft palate
      association may have arisen by chance given the large number of comparisons made
      in the study. Error appears unlikely as an explanation of the association. The
      assessment of causation in teratology uses a systematic evaluation based on the
      Hill criteria or similar criteria of Shepard or Brent. 

PMID- 24095702
TI  - Assessing the impact of the urbanization process on net primary productivity in
      China in 1989-2000.
AB  - Urban development affects the material circulation and energy flow of ecosystems,
      thereby affecting the Net Primary Productivity (NPP). The loss of NPP due to
      urban expansion was calculated integrating GLO-PEM with remote sensing and GIS
      techniques in China during the period of 1989-2000. Using urban expansion and the
      mean NPP for the different land use types in the fourteen regions, the total loss
      of NPP was calculated as 0.95 Tg C, which accounted for 0.03% of the national NPP
      of 1989. The total loss of NPP due to the transformation from cropland to urban
      land accounted for 91.93%, followed by forest (7.17%) and grassland (0.69%).
      However, the conversion from unused land, industrial and construction land, and
      water bodies to urban land resulted in an increase in the NPP. The regions
      locating in eastern China and middle China had large reductions in the total NPP
      due to urban expansion. 

PMID- 24095703
TI  - Serum biomarkers of polyfluoroalkyl compound exposure in young girls in Greater
      Cincinnati and the San Francisco Bay Area, USA.
AB  - PFC serum concentrations were measured in 6-8 year-old girls in Greater
      Cincinnati (GC) (N = 353) and the San Francisco Bay Area (SFBA) (N = 351). PFOA
      median concentration was lower in the SFBA than GC (5.8 vs. 7.3 ng/mL). In GC,
      48/51 girls living in one area had PFOA concentrations above the NHANES 95th
      percentile for children 12-19 years (8.4 ng/mL), median 22.0 ng/mL. The duration
      of being breast fed was associated with higher serum PFOA at both sites and with
      higher PFOS, PFHxS and Me-PFOSA-AcOH concentrations in GC. Correlations of the
      PFC analytes with each other suggest that a source upriver from GC may have
      contributed to exposures through drinking water, and water treatment with
      granular activated carbon filtration resulted in less exposure for SWO girls
      compared to those in NKY. PFOA has been characterized as a drinking water
      contaminant, and water treatment systems effective in removing PFCs will reduce
      body burdens.

PMID- 24095704
TI  - Detection and differentiation of pollution in urban surface soils using magnetic
      properties in arid and semi-arid regions of northwestern China.
AB  - Increasing urbanization and industrialization over the world has caused many
      social and environmental problems, one of which drawing particular concern is the
      soil pollution and its ecological degradation. In this study, the efficiency of
      magnetic methods for detecting and discriminating contaminates in the arid and
      semi-arid regions of northwestern China was investigated. Topsoil samples from
      six typical cities (i.e. Karamay, Urumqi, Lanzhou, Yinchuan, Shizuishan and
      Wuhai) were collected and a systematic analysis of their magnetic properties was
      conducted. Results indicate that the topsoil samples from the six cities were all
      dominated by coarse low-coercivity magnetite. In addition, the average magnetite
      contents in the soils from Urumqi and Lanzhou were shown to be much higher than
      those from Karamay, Yinchuan, Shizuishan and Wuhai, and they also have relatively
      higher chilf and chifd% when compared with cities in eastern China. Moreover,
      specific and distinctive soil pollution signals were identified at each sampling
      site using the combined various magnetic data, reflecting distinct sources.
      Industrial and traffic-derived pollution was dominant in Urumqi and Lanzhou, in
      Yinchuan industrial progress was observed to be important with some places
      affected by vehicle emission, while Karamay, Shizuishan and Wuhai were relatively
      clean. The magnetic properties of these latter three cities are significantly
      affected by both anthropogenic pollution and local parent materials from the
      nearby Gobi desert. The differences in magnetic properties of topsoil samples
      affected by mixed industrial and simplex traffic emissions are not obvious, but
      significant differences exist in samples affected by simplex industrial/vehicle
      emissions and domestic pollution. The combined magnetic analyses thus provide a
      sensitive and powerful tool for classifying samples according to likely sources,
      and may even provide a valuable diagnostic tool for discriminating among
      different cities. 

PMID- 24095705
TI  - Concentrations of prioritized pharmaceuticals in effluents from 50 large
      wastewater treatment plants in the US and implications for risk estimation.
AB  - We measured concentrations of 56 active pharmaceutical ingredients (APIs) in
      effluent samples from 50 large wastewater treatment plants across the US.
      Hydrochlorothiazide was found in every sample. Metoprolol, atenolol, and
      carbamazepine were found in over 90% of the samples. Valsartan had the highest
      concentration (5300 ng/L), and also had the highest average concentration (1600
      ng/L) across all 50 samples. Estimates of potential risks to healthy human adults
      were greatest for six anti-hypertensive APIs (lisinopril, hydrochlorothiazide,
      valsartan, atenolol, enalaprilat, and metoprolol), but nevertheless suggest risks
      of exposure to individual APIs as well as their mixtures are generally very low.
      Estimates of potential risks to aquatic life were also low for most APIs, but
      suggest more detailed study of potential ecological impacts from four analytes
      (sertraline, propranolol, desmethylsertraline, and valsartan). 

PMID- 24095706
TI  - Embryonic exposure of medaka (Oryzias latipes) to propylparaben: effects on early
      development and post-hatching growth.
AB  - Here we proposed a battery of non-invasive biomarkers and a histological survey
      to examine physiological/anatomical features in embryos, eleutheroembryos (13
      days post-fertilization, dpf), and larvae (28-42 dpf) of medaka to investigate
      the effects of embryonic exposure to propylparaben (PrP). Concentrations <1000
      MUg PrP/L didn't exert early or late toxic effects. However, survivorship was
      affected at 4000 MUg/L in eleutheroembryos and at >=1000 MUg/L in larvae.
      Histological alterations were found in 37.5% of eleutheroembryos exposed to 4000
      MUg PrP/L. Morphometric analysis of the gallbladder revealed significant dilation
      at >=400 MUg/L throughout embryo development. Ethoxyresorufin-O-deethylase
      (EROD), as indicator of cytochrome P4501A activity, didn't reveal
      induction/inhibition although its combination with a P4501A agonist (i.e. beta
      naphthoflavone) resulted in a synergic EROD response. Results suggest a low
      toxicity of PrP for fish and support the use of fish embryos and eleutheroembryos
      as alternatives of in vivo biomarkers indicative of exposure/toxicity. 

PMID- 24095707
TI  - Active and passive-touch during interpersonal multisensory stimulation change
      self-other boundaries.
AB  - In the "enfacement" illusion seeing an unfamiliar face being touched at the same
      time as one's own face evokes changes in self-face recognition. We investigated
      the contribution of proprioceptive and motor signals derived from self-generated
      actions in the sensory-driven malleability of self-other boundaries during the
      "enfacement" illusion. Changes in self-face recognition during active- and
      passive-touch interpersonal visuo-tactile stimulation were quantified by means of
      psychophysical and psychometric tasks. Active- and passive-touch evoked
      comparable changes in the categorical boundaries of self-other distinction,
      changing the extent to which the other is assimilated into the mental self
      representation. Actively touching or simply feeling touch on one's own face with
      concurrent observed touch on someone else's face seems to elicit comparable
      changes in self-recognition, suggesting that afferent input might be sufficient
      for updating one's body-image, although some components of the experience of self
      identification seem to be more affected by passive- than by active-touch. 

PMID- 24095708
TI  - Experiences of activity and causality in schizophrenia: when predictive deficits
      lead to a retrospective over-binding.
AB  - In this paper I discuss an intriguing and relatively little studied symptomatic
      expression of schizophrenia known as experiences of activity in which patients
      form the delusion that they can control some external events by the sole means of
      their mind. I argue that experiences of activity result from patients being prone
      to aberrantly infer causal relations between unrelated events in a retrospective
      way owing to widespread predictive deficits. Moreover, I suggest that such
      deficits may, in addition, lead to an aberrant intentional binding effect i.e.,
      the subjective compression of the temporal interval between an intentional action
      and its external effects (Haggard, Clark, & Kalogeras, 2002). In particular, it
      might be that patient's thoughts are bound to the external events they aimed to
      control producing, arguably, a temporal contiguity between these two components.
      Such temporal contiguity would reinforce or sustain the (causal) feeling that the
      patient mind is directly causally efficient. 

PMID- 24095710
TI  - Sensorial suppression of self-generated sounds and its dependence on attention.
AB  - The auditory processing of self-generated sounds is characterized by an
      attenuated vertex N1-component of the event-related potential (ERP) compared to
      the responses elicited by externally generated sounds. Typically, a motor
      condition where sounds are actively produced by button presses is compared with a
      passive listening condition. While this effect is usually interpreted as
      reflection of an internal forward model system, the impact of attention and
      arousal on the so called self-generation effect has not been systematically
      controlled in these studies: Is the auditory stimulation more attended during the
      active task compared to passive listening, e.g., caused by a higher arousal
      level? Or is it rather attended less and attention is drawn away from the task
      irrelevant stimulation to the motor task? Accordingly, the self-generation
      effects reported in the literature can easily be over- or underestimated. In the
      present study we disentangled attention from the self-generation effect by
      introducing an active listening condition, in which attention is focused to the
      same feature as in the self-generation condition - the stimulus onset-to-onset
      interval. We observed a classical 'self-generation effect', i.e. attenuated
      amplitudes for self-generated compared to passive listened sounds at
      frontocentral electrodes. As expected this effect was overlapped by attention
      effects in space and time. However, topographical and tomographical analyses
      allowed us to clearly disentangle both effects. Our results argue for the
      existence of a genuine self-generation effect, but emphasize the problem of
      possible over- or underestimation caused by attentional confounds. 

PMID- 24095709
TI  - Lineage specifiers: new players in the induction of pluripotency.
AB  - Pluripotency-associated factors and their rivals, lineage specifiers, have long
      been considered the determining factors for the identity of pluripotent and
      differentiated cells, respectively. Therefore, factors that are employed for
      cellular reprogramming in order to induce pluripotency have been identified
      mainly from embryonic stem cell (ESC)-enriched and pluripotency-associated
      factors. Recently, lineage specifiers have been identified to play important
      roles in orchestrating the process of restoring pluripotency. In this review, we
      summarize the latest discoveries regarding cell fate conversion using
      pluripotency-associated factors and lineage specifiers. We highlight the value of
      the "seesaw" model in defining cellular identity, opening up a novel scenario to
      consider pluripotency and lineage specification. 

PMID- 24095711
TI  - Chitosan scaffolds containing chicken feather keratin nanoparticles for bone
      tissue engineering.
AB  - Chicken feathers are considered as major waste from poultry industry. They are
      mostly constituted by a protein called keratin. In this study, keratin was
      prepared from chicken feathers and from where keratin nanoparticles (nKer) were
      synthesized. Since chitosan has excellent properties like controlled
      biodegradation and biocompatibility, we used keratin nanoparticles along with
      chitosan matrix as scaffolds (CS/nKer) and they were characterized by SEM, FT-IR
      and XRD analyses. There was a porous architecture in the scaffolds in the range
      to support cell infiltration and tissue ingrowth. The keratin nanoparticles had
      interaction with chitosan matrix and did not alter the semi crystalline nature of
      chitosan scaffolds. The biodegradation and protein adsorption of the scaffolds
      were significantly increased upon addition of keratin nanoparticles. The
      scaffolds were also found to be non-cytotoxic to human osteoblastic cells. Thus,
      CS/nKer scaffolds could serve as a potential biomimetic substrate for bone tissue
      engineering applications. 

PMID- 24095712
TI  - Synergistic solubilization of porcine myosin in physiological salt solution by
      arginine.
AB  - Myosin is an important protein resource for food industries and has a bipolar
      filamentous structure that is composed of subfilaments that occur in vivo. It has
      been shown that a high ionic strength is required to prevent myosin from forming
      filamentous structures and to solubilize the protein in aqueous solution. In the
      presence of 100-200 mM NaCl, 50 mM arginine was more effective than other
      additives tested, including NaCl, in myosin solubilization. Before reaching
      equilibrium solubility, the myosin solution was initially supersaturated upon the
      dilution of a stock myosin solution in 1 M NaCl into the test solvents. Arginine
      slowed the process of equilibration and stabilized the supersaturated solution
      more effectively than other additives. No structural changes in myosin caused by
      arginine were observed, which indicated that arginine enhanced the solubility of
      myosin in a physiological salt solution without affecting the structure.

PMID- 24095713
TI  - Behavior of Plasmodium falciparum purine nucleoside phosphorylase in
      macromolecular crowded environment.
AB  - Biochemical and biophysical properties of enzymes have been studied in dilute
      buffer system, which are far from the crowded physiological condition of cell. We
      report the enzyme kinetics and refolding of Plasmodium falciparum purine
      nucleoside phosphorylase under crowded conditions. Enzyme catalytic efficiency
      was inversely affected in the presence of polyethylene glycols and Dextran
      whereas it was increased in the presence of osmolytes. We detected a non-linear
      relationship between Km and increasing macromolecular crowding agents. At low
      concentrations of PEGs and Dextran, we observed decreased substrate binding
      whereas higher concentrations of PEGs and Dextran favored substrate binding. The
      presence of sucrose decreased the Km values. We detected decrease in Kcat value
      in the presence of PEGs and Dextran, whereas osmolytes increased the Kcat values.
      Thermal resistance of enzyme was increased in the presence of crowding agents.
      Intrinsic and extrinsic fluorescence analysis indicated change around active site
      loop region having single tryptophan residue. Preferential exclusions of polyols
      favor the catalytic mechanism of the enzyme. Urea denatured enzyme showed fast
      refolding when diluted and rate of refolding was not affected by the presence of
      crowding agents. It is important to draw together significant knowledge about
      modulation of inherent properties of this enzyme in crowded environment which
      will be helpful in better understanding of this drug-target enzyme and in further
      inhibitor design. 

PMID- 24095714
TI  - Identification of a novel interacting partner of the chemosensory protein 1 from
      Plutella xylostella L.
AB  - Chemosensory proteins (CSPs) are small soluble proteins endowed with
      heterogeneous functions. The information so far available for CSPs suggested
      these well-defined and conserved proteins were involved in diverse activities,
      including chemical communication, feeding, development, mating, immune
      regulation, as well as circadian rhythms. However, the detailed mechanisms of
      these physiological functions remain elusive. To explore the underlying
      mechanisms of CSPs and their interaction partners, a cDNA library from the head
      of Plutella xylostella was screened against CSP1 to identify proteins involved in
      the PxylCSP1-related physiological activities. Protein kinase C (PKC) was
      screened out as a putative interacting protein of PxylCSP1. The full length of
      PxylPKC cDNA was obtained, and the results of semi-quantitative real-time PCR and
      quantitative real-time PCR revealed that PxylPKC showed similar expression
      pattern as PxylCSP1. In vivo and in vitro interactions between PxylCSP1 and
      PxylPKC were further confirmed by co-immunoprecipitation and GST pull-down
      assays, respectively. These findings extended our knowledge on the mechanisms of
      CSP-regulated functions, and providing new target proteins to facilitate the
      design of novel intervention strategies against the pest. 

PMID- 24095715
TI  - Method qualification and application of diffusion interaction parameter and
      virial coefficient.
AB  - This research focused on evaluation and application of two methods in studying
      weak protein-protein interactions, i.e. diffusion interaction parameter (KD) and
      second virial coefficient (B22), both of which are first-order coefficients of
      protein interactions. Although the plate-based KD method successfully
      distinguished KD values with relatively large difference in a pH ranging study,
      it failed to make a consistent statistical decision to determine close
      interactions as shown by the comprehensive ANOVA analysis. We also validated the
      DLS-based B22 method by using a model protein lysozyme. The dramatic change of
      solution appearance for lysozyme as a function of NaCl concentration highlighted
      the importance of B22 in understanding protein interactions. Moreover, B22
      measurement for a MAb fragment suggested a more repulsive protein interaction in
      histidine buffer than in citrate buffer. The coefficient of variation was <10%
      when B22 was on an order of magnitude of 10(-4) L mmol/g(2) in contrast to >30%
      when it approached 10(-5) L mmol/g(2). In this research, we also made an attempt
      to study protein-protein interactions in concentrated MAb fragment solutions
      (e.g. >50 mg/mL). Our data suggested that such interactions could be empirically
      modeled by high-order virial expansions.

PMID- 24095717
TI  - Green nanotechnology - a new hope for medical biology.
AB  - The development of eco-friendly technologies in material synthesis is of
      considerable importance to expand their biological applications. Nowadays, a
      variety of green nanoparticles with well-defined chemical composition, size, and
      morphology have been synthesized by different methods and their applications in
      many cutting-edge technological areas have been explored. This review highlights
      the classification of nanoparticles giving special emphasis on biosynthesis of
      metal nanoparticle by viable organisms. It also focuses on the applications of
      these biosynthesized nanoparticles in a wide spectrum of potential areas of
      medical biology including catalysis, targeted drug delivery, cancer treatment,
      antibacterial agents and as biosensors. 

PMID- 24095716
TI  - The relationship between DNA adduct formation by benzo[a]pyrene and expression of
      its activation enzyme cytochrome P450 1A1 in rat.
AB  - Benzo[a]pyrene (BaP) is a human carcinogen requiring metabolic activation prior
      to reaction with DNA. Cytochrome P450 (CYP) 1A1 is the most important hepatic and
      intestinal enzyme in both BaP activation and detoxification. CYP1A2 is also
      capable of oxidizing BaP, but to a lesser extent. The induction of CYP1A1/2 by
      BaP and/or beta-naphthoflavone in liver and small intestine of rats was
      investigated. Both BaP and beta-naphthoflavone induced CYP1A expression and
      increased enzyme activities in both organs. Moreover, the induction of CYP1A
      enzyme activities resulted in an increase in formation of BaP-DNA adducts
      detected by (32)P-postlabeling in rat liver and in the distal part of small
      intestine in vivo. The increases in CYP1A enzyme activity were also associated
      with bioactivation of BaP and elevated BaP-DNA adduct levels in ex vivo
      incubations of microsomes of both organs with DNA and BaP. These findings
      indicate a stimulating effect of both compounds on BaP-induced carcinogenesis. 

PMID- 24095718
TI  - Differential influences of various arsenic compounds on antioxidant defense
      system in liver and kidney of rats.
AB  - In this study, oxidative stress-related parameters and As retention were examined
      in liver and kidneys of male Wistar rats exposed to arsenic trioxide, sodium
      arsenite (iAsIII), sodium arsenate (iAsV), and dimethylarsinic acid (DMAsV) at a
      single ip dose of 3.8 mgAs/kgbw, at 24h post-exposure. In liver, lipid
      peroxidation increased in iAsIII-exposed rats, glutathione peroxidase activity
      decreased in inorganic arsenic (iAs)-exposed rats, and catalase and thioredoxin
      reductase activities decreased significantly in all As-exposed groups. Both
      As(III) and As(V) exposure elevated GSH level with no effect on glutathione
      reductase activity. In kidneys, catalase activity decreased significantly in iAs
      exposed, rats; GSH level, glutathione reductase and thioredoxin reductase
      activity decreased in DMAsV-treated, rats. The tissue As retention was higher in
      kidneys compared to liver and was also higher in As(III)-exposed compared to
      As(V)-exposed rats. The results demonstrate similar potency of inorganic As(III)
      and As(V) compounds to inhibit/induce antioxidant defense system, with liver
      being more vulnerable to acute As(III)- and As(V)-induced oxidative stress.

PMID- 24095719
TI  - [Comparative cost analysis of molecular biology methods in the diagnosis of
      sarcomas].
AB  - Sarcomas represent a complex and heterogeneous group of rare malignant tumors and
      their correct diagnosis is often difficult. Recent molecular biological
      techniques have been of great diagnostic use and there is a need to assess the
      cost of these procedures in routine clinical practice. Using prospective and
      observational data from eight molecular biology laboratories in France, we used
      "microcosting" method to assess the cost of molecular biological techniques in
      the diagnosis of five types of sarcoma. The mean cost of fluorescence in situ
      hybridization (FISH) was 318 ? (273-393) per sample; mean reverse transcription
      polymerase chain reaction (RT-PCR) cost ranged from 300 ? (229-481) per formalin
      fixed, paraffin-embedded specimen to 258 ? (213-339) per frozen specimen; mean
      quantitative polymerase chain reaction (Q-PCR) cost was 184 ? (112-229) and mean
      CGH-array cost was 332 ? (329-335). The cost of these recently implemented
      techniques varied according to the type of sarcoma; the method of tissue
      collection and local organizational factors including the level of local
      expertise and investment. The cost of molecular diagnostic techniques needs to be
      balanced against their respective performance.

PMID- 24095720
TI  - Inhibition of STIM1 phosphorylation underlies resveratrol-induced inhibition of
      store-operated calcium entry.
AB  - Resveratrol, a natural phytoalexin that shows health-promoting benefits, is an
      inhibitor of store-operated calcium entry (SOCE). Knowledge of the molecular
      mechanism underlying this inhibition is required for the proper design of
      therapies that include resveratrol or related stilbenoids, but remains largely
      unknown. To unravel this mechanism, using HEK293 cells as a model, we found that
      resveratrol inhibited the ERK1/2 activation triggered by Ca2+ store depletion. As
      a consequence, resveratrol inhibited STIM1 phosphorylation at residues Ser575,
      Ser608, and Ser621. Because this phosphorylation regulates the dissociation of
      STIM1 from the microtubule plus-end binding protein EB1 under store depletion
      conditions, resveratrol inhibited STIM1-EB1 dissociation. This inhibition had
      downstream effects such as inhibition of STIM1 multimerization in response to
      store depletion, and a significant impairment in the binding of STIM1 to ORAI1.
      Although additional targets for resveratrol in the molecular mechanism that
      governs SOCE cannot be discarded, the present results demonstrate that ERK1/2
      pathway is a major target for resveratrol, and that the impairment of its
      activation produces a significant inhibition of SOCE.

PMID- 24095721
TI  - Elimination of macrophages drives LXR-induced regression both in initial and
      advanced stages of atherosclerotic lesion development.
AB  - While numerous studies have aimed to develop strategies to inhibit the
      development and progression of atherosclerosis, recent attention has focussed on
      the regression of pre-existing atherosclerotic plaques. As important regulator of
      total body cholesterol homeostasis, the liver X receptor (LXR) could possibly be
      an important target to induce regression. Here, we describe the effect of LXR
      activation by the synthetic agonist T0901317 on lesion regression in different
      mouse models with early fatty streak lesions or advanced collagen-rich lesions.
      Although T0901317 caused a dramatic increase in plasma (V)LDL levels in low
      density lipoprotein (LDL) receptor knockout mice, no further increase in lesion
      size was observed, which points to beneficial LXR activity in the vascular wall.
      In normolipidemic C57BL/6 mice with cholate diet-induced atherosclerotic lesions,
      T0901317 treatment improved plasma lipoprotein levels and induced lesion
      regression (-43%, p<0.05). Apolipoprotein E (APOE) reconstitution in APOE
      knockout mice by means of bone marrow transplantation dramatically improved
      plasma lipoprotein profiles and resulted in a marked regression of initial (-45%,
      p<0.001) and advanced lesions (-23%, p<0.01). Atherosclerosis regression was
      associated with a decrease in the absolute macrophage content (-84%, p<0.001).
      T0901317 supplementation further decreased the size of early (-71%, p<0.001 vs
      baseline; -48%, p<0.01 vs chow diet alone) and more advanced atherosclerotic
      lesions (-36%, p<0.001 and -17%, p=0.06 respectively). In conclusion, our study
      highlights the potential of LXR agonist T0901317 to stimulate removal of
      macrophages from atherosclerotic lesions ultimately leading to a highly
      significant plaque regression of both early and advanced atherosclerotic lesions.

PMID- 24095722
TI  - Dendritic integration in pyramidal neurons during network activity and disease.
AB  - Neurons have intricate dendritic morphologies which come in an array of shapes
      and sizes. Not only do they give neurons their unique appearance, but dendrites
      also endow neurons with the ability to receive and transform synaptic inputs. We
      now have a wealth of information about the functioning of dendrites which
      suggests that the integration of synaptic inputs is highly dependent on both
      dendritic properties and neuronal input patterns. It has been shown that
      dendrites can perform non-linear processing, actively transforming synaptic input
      into Na(+) spikes, Ca(2+) plateau spikes and NMDA spikes. These membrane non
      linearities can have a large impact on the neuronal output and have been shown to
      be regulated by numerous factors including synaptic inhibition. Many
      neuropathological diseases involve changes in how dendrites receive and package
      synaptic input by altering dendritic spine characteristics, ion channel
      expression and the inhibitory control of dendrites. This review focuses on the
      role of dendrites in integrating and transforming input and what goes wrong in
      the case of neuropathological diseases.

PMID- 24095723
TI  - Does sugar content matter? Blood plasma glucose levels in an occasional and a
      specialist avian nectarivore.
AB  - Nectar composition within a plant pollinator group can be variable, and bird
      pollinated plants can be segregated into two groups based on their adaptations to
      either a specialist or an occasional bird pollination system. Specialist
      nectarivores rely primarily on nectar for their energy requirements, while
      occasional nectarivores meet their energy requirements from nectar as well as
      from seeds, fruit and insects. Avian blood plasma glucose concentration (PGlu) is
      generally high compared with mammals. It is also affected by a range of factors
      including species, gender, age, ambient temperature, feeding pattern,
      reproductive status, circadian rhythm and moult status, among others. We examined
      whether sugar content affected PGlu of two avian nectarivores, a specialist
      nectarivore the Amethyst Sunbird Chalcomitra amethystina, and an occasional
      nectarivore the Cape White-eye Zosterops virens, when fed sucrose-hexose sugar
      solution diets of varying concentrations (5%-35%). Both species regulated PGlu
      within a range which was affected by sampling time (fed or fasted) and not
      dietary sugar concentration. The range in mean PGlu was broader in Amethyst
      Sunbirds (11.52-16.51mmol/L) compared with Cape White-eyes (14.33-15.85mmol/L).
      This suggests that these birds are not constrained by dietary sugar concentration
      with regard to PGlu regulation, and consequently selective pressure on plants for
      their nectar characteristics is due to reasons other than glucose regulation. 

PMID- 24095724
TI  - Energy requirements and metabolism of the Phillip's dikdik (Madoqua saltiana
      phillipsi).
AB  - Basal metabolic rates in mammals are mainly determined by body mass, but also by
      ecological factors. Some mammalian species inhabiting hot, dry environments were
      found to have lower metabolic rates compared to temperate species. We studied
      energy metabolism in Phillip's dikdik (Madoqua saltiana phillipsi), a small
      antelope inhabiting xeric shrubland habitats in the Eastern 'horn' of Africa, and
      compared results to literature data. We measured body mass (BM) changes and
      digestibility in 12 adults kept on different food intake levels to determine, by
      extrapolation to zero BM change, maintenance energy requirements (MEm) for
      metabolizable energy (ME). The MEm averaged at 404+/-20kJMEkgBM(-0.75)d(-1). In
      addition we conducted 24h-chamber respirometry with seven fed (non-fasted)
      individuals. Their mean metabolic rate as calculated from oxygen consumption was
      403+/-51kJkgBM(-0.75)d(-1), corroborating the results of the feeding experiments.
      Selecting the 20 lowest values of the respiration measurement period to estimate
      resting metabolic rate (RMR) resulted in a mean RMR of 244+/-39kJkgBM(-0.75)d(
      1), which was not significantly lower than the expected basal metabolic rate of
      293kJkgBM(-0.75)d(-1). Therefore, resting metabolism was similar to the expected
      average basal metabolism of a mammal of this size, which suggests a comparatively
      low metabolic rate in dikdiks. Compared to literature data Phillip's dikdiks have
      a MEm similar to measurements reported for small domestic ruminants, but
      considerably lower than those reported for other wild ruminant species inhabiting
      temperate and cold climates. 

PMID- 24095725
TI  - Reactive oxygen species exacerbate autoimmune hemolytic anemia in New Zealand
      Black mice.
AB  - Elevated reactive oxygen species (ROS) and oxidative damage occur in the red
      blood cells (RBCs) of SOD1-deficient C57BL/6 mice. This leads to autoimmune
      responses against RBCs in aged mice that are similar to autoimmune hemolytic
      anemia (AIHA). We examined whether a SOD1 deficiency and/or the human SOD1
      transgene (hSOD1) would affect phenotypes of AIHA-prone New Zealand Black (NZB)
      mice by establishing three congenic strains: those lacking SOD1, those expressing
      hSOD1 under a GATA-1 promoter, and those lacking mouse SOD1 but expressing hSOD1.
      Levels of intracellular ROS and oxidative stress markers increased, and the
      severity of the AIHA phenotype was aggravated by a SOD1 deficiency. In contrast,
      the transgenic expression of hSOD1 in an erythroid cell-specific manner averted
      most of the AIHA phenotype evident in the SOD1-deficient mice and also
      ameliorated the AIHA phenotype in the mice possessing intrinsic SOD1. These data
      suggest that oxidative stress in RBCs may be an underlying mechanism for
      autoimmune responses in NZB mice. These results were consistent with the
      hypothetical role of reactive oxygen species in triggering the autoimmune
      reaction in RBCs and may provide a novel approach to mitigating the progression
      of AIHA by reducing oxidative stress. 

PMID- 24095726
TI  - A functional link between heme oxygenase-1 and tristetraprolin in the anti
      inflammatory effects of nicotine.
AB  - Nicotine stimulates the cholinergic anti-inflammatory pathway and prevents
      excessive inflammation by inhibiting the release of inflammatory cytokines from
      macrophages. We have previously reported that heme oxygenase-1 (HO-1) and
      tristetraprolin (TTP) are induced by nicotine and mediate the anti-inflammatory
      function of nicotine in macrophages. However, it was not clear whether the two
      molecules are functionally linked. In this study, we sought to determine whether
      HO-1 associates with TTP to mediate the anti-inflammatory effects of nicotine.
      Inhibition of HO-1 activity or HO-1 expression attenuated the effects of nicotine
      on STAT3 activation, TTP induction, and TNF-alpha production in LPS-treated
      macrophages. Induction of HO-1 expression increased the level of TTP in the
      absence of nicotine. In an LPS-induced endotoxemia model, HO-1 deficiency blocked
      the effects of nicotine on the STAT3 phosphorylation, TTP induction, and LPS
      induced TNF-alpha production in the liver. Downregulation of STAT3 by siRNA
      attenuated the effect of nicotine on TTP expression and TNF-alpha production but
      did not affect the nicotine-mediated induction of HO-1. In TTP knockout mice,
      nicotine treatment enhanced HO-1 expression and STAT3 activation but failed to
      inhibit LPS-induced TNF-alpha production. Our results suggest that HO-1 and TTP
      are functionally linked in mediating the anti-inflammatory effects of nicotine;
      HO-1 is necessary for the induction of TTP by nicotine. This novel nicotine-HO-1
      TTP signaling pathway provides new possibilities for the treatment of
      inflammatory diseases. 

PMID- 24095728
TI  - Screening for perinatal depression.
AB  - Perinatal depression is prevalent, under-diagnosed and can have serious long-term
      effects on the wellbeing of women, their partners and infants. In the absence of
      active identification strategies, most women with perinatal depression will
      neither seek nor receive help. To enable early detection and timely intervention,
      universal screening is coming to be seen as best practice in many settings.
      Although the strength of recommendations and the preferred methods of
      identification vary in different countries (e.g. the Edinburgh Postnatal
      Depression Scale, brief case-finding questions), appropriate training for health
      professionals in wider psychosocial assessment is essential to maximise
      usefulness while minimising potential harms. Clear pathways of systematic follow
      up of all positive screening results with a diagnostic procedure and access to
      effective treatment are centrally important both for the clinical effectiveness
      of screening and for health system costs. It is also necessary to further build
      on the emerging evidence base for the clinical effectiveness of screening. 

PMID- 24095727
TI  - Increased autophagy in peripheral nerves may protect Wistar Ottawa Karlsburg W
      rats against neuropathy.
AB  - OBJECTIVE: Wistar Ottawa Karlsburg W (RT1(u)) rats (WOKW) develop obesity,
      dyslipidemia, moderate hypertension, hyperinsulinemia and impaired glucose
      tolerance prone to induce peripheral neuropathy (PN). Autophagy has been shown to
      prevent neurodegeneration in the central and peripheral nervous system. We
      analyzed the potential protective role of autophagy in an established rat model
      in preventing PN. METHODS: We examined electrophysiology (motor-and sensory/mixed
      afferent conduction velocities and the minimal F-wave latency) and morphology,
      including ultrathin sections, myelin sheath thickness (g-ratio) and
      immunohistochemical markers of autophagy and inflammation in the sciatic nerve of
      five-month-old, male WOKW as compared to Wistar derived, congenic LEW.1W control
      rats, characterized by the same major histocompatibility complex as WOKW rats
      (RT1(u)). Moreover, the expression of axonal and synaptic proteins (NF68, GAP43,
      MP0), autophagy- (Atg5, Atg7, LC3), and apoptosis (cleaved caspase-3)-related
      markers was measured using Western blot. RESULTS: No abnormalities in nerve
      electrophysiology and morphology were found in WOKW compared to LEW.1W rats.
      However, autophagosomes were more frequently apparent in sciatic nerves of WOKW
      rats. In Western blot analyses no significant differences in expression of
      neuronal structural proteins were found, but autophagy markers were up-regulated
      in WOKW compared to LEW.1W sciatic nerves. Immunostaining revealed a greater
      infiltration of Iba1/ED-1-positive macrophages, CD-3-positive T-cells and LC3
      expression in sciatic nerves of WOKW rats. CONCLUSIONS: Our results indicate that
      WOKW rats show an up-regulated autophagy and a mild inflammatory response but do
      not develop overt neuropathy. We suggest that autophagy and inflammatory cells
      may exert a protective role in preventing neuropathy in this rat model of the
      metabolic syndrome but the mechanism of action is still unclear.

PMID- 24095729
TI  - Structural insights into RIP3-mediated necroptotic signaling.
AB  - RIP3 is an essential upstream kinase in necroptosis. The pseudokinase MLKL
      functions as a substrate of RIP3 to mediate downstream signaling. The molecular
      mechanism by which RIP3 recognizes and phosphorylates MLKL remains unknown. Here,
      we report the crystal structures of the mouse RIP3 kinase domain, the MLKL kinase
      like domain, and a binary complex between the two. Both RIP3 and MLKL adopt the
      canonical kinase fold. Free RIP3 exists in an active conformation, whereas MLKL
      bound RIP3 is stabilized by AMP-PNP to adopt an inactive conformation. The
      formation of the RIP3-MLKL complex, involving their respective N- and C-lobes, is
      accompanied by pronounced conformational changes of the alphaC helix and
      activation loop in RIP3 and the corresponding structural elements in MLKL. RIP3
      mediated MLKL phosphorylation, though important for downstream signaling, is
      dispensable for stable complex formation between RIP3 and MLKL. Our study serves
      as a framework for mechanistic understanding of RIP3-mediated necroptotic
      signaling. 

PMID- 24095730
TI  - Analysis of in vitro insulin-resistance models and their physiological relevance
      to in vivo diet-induced adipose insulin resistance.
AB  - Diet-induced obesity (DIO) predisposes individuals to insulin resistance, and
      adipose tissue has a major role in the disease. Insulin resistance can be induced
      in cultured adipocytes by a variety of treatments, but what aspects of the in
      vivo responses are captured by these models remains unknown. We use global RNA
      sequencing to investigate changes induced by TNF-alpha, hypoxia, dexamethasone,
      high insulin, and a combination of TNF-alpha and hypoxia, comparing the results
      to the changes in white adipose tissue from DIO mice. We found that different in
      vitro models capture distinct features of DIO adipose insulin resistance, and a
      combined treatment of TNF-alpha and hypoxia is most able to mimic the in vivo
      changes. Using genome-wide DNase I hypersensitivity followed by sequencing, we
      further examined the transcriptional regulation of TNF-alpha-induced insulin
      resistance, and we found that C/EPBbeta is a potential key regulator of adipose
      insulin resistance. 

PMID- 24095732
TI  - IFT88 plays a cilia- and PCP-independent role in controlling oriented cell
      divisions during vertebrate embryonic development.
AB  - The role for cilia in establishing planar cell polarity (PCP) is contentious.
      Although knockdown of genes known to function in ciliogenesis has been reported
      to cause PCP-related morphogenesis defects in zebrafish, genetic mutations
      affecting intraflagellar transport (IFT) do not show PCP phenotypes despite the
      requirement for IFT in cilia formation. This discrepancy has been attributed to
      off-target effects of antisense morpholino oligonucleotide (MO) injection,
      confounding maternal effects in zygotic mutant embryos, or an inability to
      distinguish between cilia-dependent versus cilia-independent protein functions.
      To determine the role of cilia in PCP, we generated maternal + zygotic IFT88
      (MZift88) mutant zebrafish embryos, which never form cilia. We clearly
      demonstrate that cilia are not required to establish PCP. Rather, IFT88 plays a
      cilia-independent role in controlling oriented cell divisions at gastrulation and
      neurulation. Our results have important implications for the interpretation of
      cilia gene function in normal development and in disease. 

PMID- 24095731
TI  - TRF2 interaction with Ku heterotetramerization interface gives insight into c
      NHEJ prevention at human telomeres.
AB  - Telomeres are protected from nonhomologous end-joining (NHEJ) to avoid
      deleterious chromosome fusions, yet they associate with the Ku heterodimer that
      is principal in the classical NHEJ (c-NHEJ) pathway. T-loops have been proposed
      to inhibit Ku's association with telomeric ends, thus inhibiting c-NHEJ; however,
      deficiencies in the t-loop model suggest additional mechanisms are in effect. We
      demonstrate that TRF2 interacts with Ku at telomeres and via residues in Ku70
      helix 5 (alpha5), which are vital for NHEJ. We show that Ku's interaction with a
      TRF2 mutant that induces telomeric fusions is significantly impaired.
      Additionally, we demonstrate that Ku70 alpha5 is required for Ku self-association
      in live cells, which can bridge DNA ends. Together, these findings lead us to
      propose a model in which telomeres are directly protected from c-NHEJ via TRF2
      impeding Ku's ability to synapse telomere ends. 

PMID- 24095733
TI  - Molecular basis for the regulation of the H3K4 methyltransferase activity of
      PRDM9.
AB  - PRDM9, a histone lysine methyltransferase, is a key determinant of the
      localization of meiotic recombination hot spots in humans and mice and the only
      vertebrate protein known to be involved in hybrid sterility. Here, we report the
      crystal structure of the PRDM9 methyltransferase domain in complex with a histone
      H3 peptide dimethylated on lysine 4 (H3K4me2) and S-adenosylhomocysteine
      (AdoHcy), which provides insights into the methyltransferase activity of PRDM
      proteins. We show that the genuine substrate of PRDM9 is histone H3 lysine 4
      (H3K4) and that the enzyme possesses mono-, di-, and trimethylation activities.
      We also determined the crystal structure of PRDM9 in its autoinhibited state,
      which revealed a rearrangement of the substrate and cofactor binding sites by a
      concerted action of the pre-SET and post-SET domains, providing important
      insights into the regulatory mechanisms of histone lysine methyltransferase
      activity. 

PMID- 24095734
TI  - CAST-ChIP maps cell-type-specific chromatin states in the Drosophila central
      nervous system.
AB  - Chromatin organization and gene activity are responsive to developmental and
      environmental cues. Although many genes are transcribed throughout development
      and across cell types, much of gene regulation is highly cell-type specific. To
      readily track chromatin features at the resolution of cell types within complex
      tissues, we developed and validated chromatin affinity purification from specific
      cell types by chromatin immunoprecipitation (CAST-ChIP), a broadly applicable
      biochemical procedure. RNA polymerase II (Pol II) CAST-ChIP identifies ~1,500
      neuronal and glia-specific genes in differentiated cells within the adult
      Drosophila brain. In contrast, the histone H2A.Z is distributed similarly across
      cell types and throughout development, marking cell-type-invariant Pol II-bound
      regions. Our study identifies H2A.Z as an active chromatin signature that is
      refractory to changes across cell fates. Thus, CAST-ChIP powerfully identifies
      cell-type-specific as well as cell-type-invariant chromatin states, enabling the
      systematic dissection of chromatin structure and gene regulation within complex
      tissues such as the brain.

PMID- 24095735
TI  - Expression of BCR/ABL p210 from a knockin allele enhances bone marrow engraftment
      without inducing neoplasia.
AB  - Chronic myeloid leukemia (CML) and some acute lymphoblastic leukemias are
      characterized by the t(9;22) chromosome, which encodes the BCR/ABL oncogene.
      Multiple mouse models of CML express BCR/ABL at high levels from non-Bcr
      promoters, resulting in the development of leukemias. In contrast, a significant
      fraction of healthy humans have been found to have BCR/ABL-positive hematopoietic
      cells. To bridge the gap between the information derived from current mouse
      models and nonleukemic humans with the BCR/ABL oncogene, we generated a knockin
      model with BCR/ABL p210 expressed from the Bcr locus. Unlike previous models,
      expression of BCR/ABL from the knockin allele did not induce leukemia. BCR/ABL
      mutant cells did exhibit favorable bone marrow engraftment compared to control
      cells. These data suggest that BCR/ABL expression alone is insufficient to induce
      disease. This model allows for inducible spatial and temporal control of BCR/ABL
      expression for analysis of early steps in the pathogenesis of BCR/ABL-expressing
      leukemias. 

PMID- 24095736
TI  - Lineage tracing and cell ablation identify a post-Aire-expressing thymic
      epithelial cell population.
AB  - Thymic epithelial cells in the medulla (mTECs) play a critical role in enforcing
      central tolerance through expression and presentation of tissue-specific antigens
      (TSAs) and deletion of autoreactive thymocytes. TSA expression requires
      autoimmune regulator (Aire), a transcriptional activator present in a subset of
      mTECs characterized by high CD80 and major histocompatibility complex II
      expression and a lack of potential for differentiation or proliferation. Here,
      using an Aire-DTR transgenic line, we show that short-term ablation specifically
      targets Aire(+) mTECs, which quickly undergo RANK-dependent recovery. Repeated
      ablation also affects Aire(-) mTECs, and using an inducible Aire-Cre fate-mapping
      system, we find that this results from the loss of a subset of mTECs that showed
      prior expression of Aire, maintains intermediate TSA expression, and
      preferentially migrates toward the center of the medulla. These results clearly
      identify a distinct stage of mTEC development and underscore the diversity of
      mTECs that play a key role in maintaining tolerance. 

PMID- 24095737
TI  - A role for BLM in double-strand break repair pathway choice: prevention of
      CtIP/Mre11-mediated alternative nonhomologous end-joining.
AB  - The choice of the appropriate double-strand break (DSB) repair pathway is
      essential for the maintenance of genomic stability. Here, we show that the Bloom
      syndrome gene product, BLM, counteracts CtIP/MRE11-dependent long-range deletions
      (>200 bp) generated by alternative end-joining (A-EJ). BLM represses A-EJ in an
      epistatic manner with 53BP1 and RIF1 and is required for ionizing-radiation
      induced 53BP1 focus assembly. Conversely, in the absence of 53BP1 or RIF1, BLM
      promotes formation of A-EJ long deletions, consistent with a role for BLM in DSB
      end resection. These data highlight a dual role for BLM that influences the DSB
      repair pathway choice: (1) protection against CtIP/MRE11 long-range deletions
      associated with A-EJ and (2) promotion of DNA resection. These antagonist roles
      can be regulated, according to cell-cycle stage, by interacting partners such as
      53BP1 and TopIII, to avoid unscheduled resection that might jeopardize genome
      integrity. 

PMID- 24095738
TI  - The serine hydrolase ABHD6 Is a critical regulator of the metabolic syndrome.
AB  - The serine hydrolase alpha/beta hydrolase domain 6 (ABHD6) has recently been
      implicated as a key lipase for the endocannabinoid 2-arachidonylglycerol (2-AG)
      in the brain. However, the biochemical and physiological function for ABHD6
      outside of the central nervous system has not been established. To address this,
      we utilized targeted antisense oligonucleotides (ASOs) to selectively knock down
      ABHD6 in peripheral tissues in order to identify in vivo substrates and
      understand ABHD6's role in energy metabolism. Here, we show that selective
      knockdown of ABHD6 in metabolic tissues protects mice from high-fat-diet-induced
      obesity, hepatic steatosis, and systemic insulin resistance. Using combined in
      vivo lipidomic identification and in vitro enzymology approaches, we show that
      ABHD6 can hydrolyze several lipid substrates, positioning ABHD6 at the interface
      of glycerophospholipid metabolism and lipid signal transduction. Collectively,
      these data suggest that ABHD6 inhibitors may serve as therapeutics for obesity,
      nonalcoholic fatty liver disease, and type II diabetes. 

PMID- 24095739
TI  - Protective roles for caspase-8 and cFLIP in adult homeostasis.
AB  - Caspase-8 or cellular FLICE-like inhibitor protein (cFLIP) deficiency leads to
      embryonic lethality in mice due to defects in endothelial tissues. Caspase-8(-/-)
      and receptor-interacting protein kinase-3 (RIPK3)(-/-), but not cFLIP(-/-) and
      RIPK3(-/-), double-knockout animals develop normally, indicating that caspase-8
      antagonizes the lethal effects of RIPK3 during development. Here, we show that
      the acute deletion of caspase-8 in the gut of adult mice induces enterocyte
      death, disruption of tissue homeostasis, and inflammation, resulting in sepsis
      and mortality. Likewise, acute deletion of caspase-8 in a focal region of the
      skin induces local keratinocyte death, tissue disruption, and inflammation.
      Strikingly, RIPK3 ablation rescues both phenotypes. However, acute loss of cFLIP
      in the skin produces a similar phenotype that is not rescued by RIPK3 ablation.
      TNF neutralization protects from either acute loss of caspase-8 or cFLIP. These
      results demonstrate that caspase-8-mediated suppression of RIPK3-induced death is
      required not only during development but also for adult homeostasis. Furthermore,
      RIPK3-dependent inflammation is dispensable for the skin phenotype. 

PMID- 24095740
TI  - Abeta secretion and plaque formation depend on autophagy.
AB  - Alzheimer's disease (AD) is a neurodegenerative disease biochemically
      characterized by aberrant protein aggregation, including amyloid beta (Abeta)
      peptide accumulation. Protein aggregates in the cell are cleared by autophagy, a
      mechanism impaired in AD. To investigate the role of autophagy in Abeta pathology
      in vivo, we crossed amyloid precursor protein (APP) transgenic mice with mice
      lacking autophagy in excitatory forebrain neurons obtained by conditional
      knockout of autophagy-related protein 7. Remarkably, autophagy deficiency
      drastically reduced extracellular Abeta plaque burden. This reduction of Abeta
      plaque load was due to inhibition of Abeta secretion, which led to aberrant
      intraneuronal Abeta accumulation in the perinuclear region. Moreover, autophagy
      deficiency-induced neurodegeneration was exacerbated by amyloidosis, which
      together severely impaired memory. Our results establish a function for autophagy
      in Abeta metabolism: autophagy influences secretion of Abeta to the extracellular
      space and thereby directly affects Abeta plaque formation, a pathological
      hallmark of AD. 

PMID- 24095741
TI  - From bacteria to human: a journey into the world of chitinases.
AB  - Chitinases, the enzymes responsible for the biological degradation of chitin, are
      found in a wide range of organisms from bacteria to higher plants and animals.
      They participate in numerous physiological processes such as nutrition,
      parasitism, morphogenesis and immunity. Many organisms, in addition to
      chitinases, produce inactive chitinase-like lectins that despite lacking
      enzymatic activity are involved in several regulatory functions. Most known
      chitinases belong to families 18 and 19 of glycosyl hydrolases, however a few
      chitinases that belong to families 23 and 48 have also been identified in recent
      years. In this review, different aspects of chitinases and chi-lectins from
      bacteria, fungi, insects, plants and mammals are discussed. 

PMID- 24095742
TI  - A comparison between free gracilis muscle flap and pedicled pectoralis major flap
      reconstructions following salvage laryngectomy.
AB  - INTRODUCTION: Muscle flaps are often used in the prevention and treatment of
      pharyngocutaneous fistula following total salvage laryngectomy in the setting of
      chemo-radiated neck for laryngeal carcinomas. We report our experience with the
      gracilis free muscle flap compared to the pedicled pectoralis major for the
      prophylaxis of fistula formation. METHODS: Forty-nine patients with radio
      recurrent laryngeal carcinoma over ten years who underwent salvage laryngectomy
      and either immediate free gracilis (22 patients) or pedicled pectoralis major
      muscle flap (27 patients) reconstruction were reviewed. RESULTS: There were 12
      complications in pectoralis major flap group and eight in gracilis flap group.
      Most of these occurred early in the post-operative period. These were related to
      poor wound healing with the pectoralis major flap reconstructions. Fistulation
      rates were similar in the two groups (Pectoralis major: 6/27, gracilis: 5/22).
      CONCLUSIONS: In our experience, the gracilis free muscle flap is a good
      reconstructive option in the prevention of pharyngocutaneous fistula formation
      following salvage laryngectomies. It is at least equivalent to a pectoralis
      muscle flap in the prevention of fistulae, but we prefer the gracilis for many
      reasons, including ease of harvest and preservation of the pectoralis major flap
      for future reconstructions.

PMID- 24095743
TI  - Whooping cough--still a challenge.

PMID- 24095744
TI  - New combination of pharmacophoric elements of potent sigma1 ligands: design,
      synthesis and sigma receptor affinity of aminoethyl substituted
      tetrahydrobenzothiophenes.
AB  - The aminoethyl substituted tetrahydrobenzothiophenes 4 resulted from combination
      of the pharmacophoric elements of the potent sigma1 ligands 2 and 3. The
      aminoethyl substituted tetrahydrobenzothiophenes 4 were prepared in an 8-step
      synthesis starting with thiophene. Whereas the sigma1 affinity of the N-benzyl
      derivative 4a is in the medium nanomolar range (Ki = 49 nM), the analogous N
      cyclohexylmethyl derivative 4d exhibits low nanomolar affinity (Ki = 5.0 nM). The
      reduced sigma1 affinity and sigma2/sigma1 selectivity of
      tetrahydrobenzothiophenes 4 compared to analogous spirocyclic piperidines 3 is
      attributed to the increased conformational flexibility of the aminoethyl side
      chain.

PMID- 24095745
TI  - Synthesis and antitumor activities of novel thiourea alpha-aminophosphonates from
      dehydroabietic acid.
AB  - A series of novel thiourea alpha-aminophosphonate derivatives containing DHA
      structure was designed and synthesized as antitumor agents. Their inhibitory
      activities against the NCI-H460 (lung), A549 (lung adenocarcinoma), HepG2 (liver)
      and SKOV3 (ovarian) human cancer cell lines were estimated using MTT assay in
      vitro. The screening results revealed that many compounds exhibited moderate to
      high levels of antitumor activities against the tested cancer cell lines and that
      most demonstrated more potent inhibitory activities compared with the commercial
      anticancer drug 5-fluorouracil. The mechanism of compound 5f was preliminarily
      investigated by acridine orange/ethidium bromide staining, Hoechst 33258
      staining, JC-1 mitochondrial membrane potential staining, TUNEL assay, DNA ladder
      assay and flow cytometry, which indicated that the compound can induce cell
      apoptosis in A549 cells.

PMID- 24095746
TI  - Anticancer evaluation of some newly synthesized N-nicotinonitrile derivative.
AB  - Some novel N-nicotinonitrile derivatives 3-14 have been synthesized starting with
      compound 1. The key step of this work is the coupling between compound 1 and
      activated sugars to afford the corresponding cyclic nucleosides 3-6. Moreover,
      the cytotoxicity and in vitro anticancer evaluation of the prepared compounds
      have also been assessed against breast MCF-7 cancer, liver HepG2 cancer and lung
      A549 carcinoma cell lines with investigation the effect of the synthesized
      compounds on the expression of urokinase plasminogen activator (uPA). The results
      revealed that, although all the compounds showed no anticancer activity against
      A549 cells without showing any effect on the expression of uPA, the tested
      compounds exhibited remarkable cytotoxicity activity against MCF-7 and HepG2 cell
      lines. Among the tested compounds, compounds 11 and 12 revealed promising
      anticancer activity compared to the activity of the commonly used anticancer
      drug, doxorubicin with inhibiting the expression of uPA.

PMID- 24095747
TI  - Design, synthesis and biological evaluation of 2-substituted quinolines as
      potential antileishmanial agents.
AB  - An analogous library of 2-substituted quinoline compounds was synthesized with
      the aim to identify a potential drug candidate to treat visceral leishmaniasis.
      These molecules were tested for their in vitro and in vivo biological activity
      against Leishmania donovani. Metabolic stability of these compounds was also
      improved through the introduction of halogen substituents. Compound (26g), found
      to be the most active; exhibited an IC50 value of 0.2 MUM and >180 fold
      selectivity. The hydrochloride salt of (26g) showed 84.26 +/- 4.44 percent
      inhibition at 50 mg/kg * 5 days (twice daily, oral route) dose in L.
      donovani/hamster model. The efficacy was well correlated with the PK data
      observed which indicating that the compound is well distributed.

PMID- 24095748
TI  - Synthesis and SAR study of novel 3,3-diphenyl-1,3-dihydroindol-2-one derivatives
      as potent eIF2.GTP.Met-tRNAiMet ternary complex inhibitors.
AB  - The growing recognition of inhibition of translation initiation as a new and
      promising paradigm for mechanism-based anti-cancer therapeutics is driving the
      development of potent, specific, and druggable inhibitors. The 3,3
      diaryloxindoles were recently reported as potential inhibitors of the
      eIF2.GTP.Met-tRNAi(Met) ternary complex assembly and 3-{5-tert-butyl-2
      hydroxyphenyl}-3-phenyl-1,3-dihydro-2H-indol-2-one #1181 was identified as the
      prototypic agent of this chemotype. Herein, we report our continuous effort to
      further develop this chemotype by exploring the structural latitude toward
      different polar and hydrophobic substitutions. Many of the novel compounds are
      more potent than the parent compound in the dual luciferase ternary complex
      reporter assay, activate downstream effectors of reduced ternary complex
      abundance, and inhibit cancer cell proliferation in the low MUM range. Moreover,
      some of these compounds are decorated with substituents that are known to endow
      favorable physicochemical properties and as such are good candidates for
      evaluation in animal models of human cancer. 

PMID- 24095749
TI  - The antitumor activity of zinc(II) and copper(II) complexes with 5,7-dihalo
      substituted-8-quinolinoline.
AB  - [Zn2(ClQ)4(CH3OH)2] (1), [Zn(BrQ)2(H2O)2] (2), [Zn2(ClIQ)4] (3) and [Cu(BrQ)2]
      (4) (H-ClQ = 5,7-dichloro-8-hydroxylquinoline, H-BrQ = 5,7-dibromo-8
      hydroxylquinoline, and H-ClIQ = 5-chloro-7-iodo-8-hydroxylquinoline) were
      synthesized. Compounds 1-4 showed high anti-proliferative cytotoxicities against
      BEL-7404, SK-OV-3, NCI-H460 tumor cells, and HL-7702 normal cells in vitro, with
      IC50 values in the 1.4 nM to 32.13 MUM range. Compounds 2-4 exhibited
      significantly enhanced cytotoxicity against BEL-7404 cell line, comparing with
      free 5,7-dihalo-8-quinolinol. Western blotting analysis showed that 2, 3 depleted
      mutant p53 protein in MDA-MB-231, and compound 2 decreased the ratio of Bcl-2/Bax
      in NCI-H460 significantly. The binding abilities of 1-4 to DNA were stronger than
      that of free quinolinol ligand. Intercalation is the probable binding mode for
      the complexes and free quinolinol ligands with DNA.

PMID- 24095750
TI  - 2-(2-Hydrazinyl)thiazole derivatives: design, synthesis and in vitro
      antimycobacterial studies.
AB  - In an attempt to discover new potent inhibitors for Mycobacterium tuberculosis
      (Mtb), a series of 2-(2-hydrazinyl)thiazole derivatives with a wide range of
      substitutions at 2-, 4- and 5-positions were designed by considering Lipinski
      rule. The designed compounds were synthesized, characterized and evaluated for
      their inhibitory potential against Mtb, H37Rv, by in vitro assay. The compounds,
      ethyl-4-methyl-2-[(E)-2-[1-(pyridin-2-yl)ethylidene]hydrazin-1-yl]-1,3-thiazole-5
      carboxylate, 4d, and ethyl-2-[(E)-2-[(2-hydroxyphenyl)methylidene]hydrazin-1-yl]
      4-methyl-1,3-thiazole-5-carboxylate, 2i showed noticeable inhibitory activity
      against Mtb, H37Rv with minimum inhibitory concentration (MIC) of 12.5 MUM and 25
      MUM respectively. An attempt has been made to understand the mechanism of action
      by binding interactions of these molecules with beta-ketoacyl-ACP synthase
      protein through docking studies. The inhibition constants for compounds 4d and 2i
      were found to be 1.46 MUM and 0.177 MUM respectively.

PMID- 24095751
TI  - Experimental and molecular modeling studies on the interaction of the Ru(II)
      piroxicam with DNA and BSA.
AB  - A mononuclear Ru(II) complex containing two piroxicam (Pir(-)) ligands was
      synthesized and fully characterized. Interaction studies of the Pir(-) anion and
      the Ru(II) complex with DNA and BSA were carried out using spectroscopic
      techniques. The results suggested that the Pir(-) anion binds to DNA in a
      moderately strong fashion via intercalation between the base stacks of double
      stranded DNA, while the Ru(II) complex is a groove binder and interacts with DNA
      with more affinity. Moreover, the results demonstrated that the microenvironment
      and the secondary structure of BSA were changed in the presence of Pir(?) and
      Ru(II) complex. The free Pir(?) ligand and the Ru(II) complex can lead to the
      photocleavage of DNA supercoiled pUC57. Finally, the binding of the Ru(II)
      complex to BSA and DNA was modeled by molecular docking and molecular dynamic
      simulation methods. 

PMID- 24095752
TI  - Synthesis, antimicrobial, antioxidant activities of novel 6-aryl-5-cyano
      thiouracil derivatives.
AB  - A series of 6-aryl-5-cyano thiouracil derivatives (2a-c to 11a-c) was synthesized
      from 6-aryl-4-hydrazino-2-thioxo-1,2-dihydropyrimidine-5-carbonitriles (1a-c).
      The products were characterized by analytical and spectral data (IR, (1)H NMR,
      (13)C NMR and mass spectra). All compounds were screened for their in-vitro
      antibacterial and antifungal activities. Compounds 7a, 7g and 9a-c showed
      pronounced antimicrobial activity than standards. Some of the newly synthesized
      compounds were evaluated for antioxidant activity. Compounds 1c, 5c and 8c
      displayed promising free radical scavenging activity and found to be more potent
      than standard, ascorbic acid (vitamin C). 

PMID- 24095753
TI  - PAMAM dendrimer derivatives as a potential drug for antithrombotic therapy.
AB  - Platelets are anucleated blood cells that play an important role both in the
      pathogenesis of atherosclerosis and subsequent thrombosis. Dendrimers have
      attracted great interest in biomedical applications. However, their interactions
      with cell compounds and compartments are nonselective, thus causing cytotoxicity
      and hemotoxicity. We derivatized PAMAM G4 and G5 dendrimers to evaluate their
      interactions with serum metabolites, their effects on the viability of red blood
      cells, and their antithrombotic properties. PAMAM G4 and G5 derivatives showed
      better hemocompatibility than the PAMAM G4 and G5 dendrimers without any
      derivatization (NH2). PAMAM G4-Arginine-Tos and G4-Lysine-Cbz act as potent
      inhibitors of platelet aggregation induced by ADP. PAMAM G4-Arginine-Tos also
      showed inhibition of platelet aggregation induced by collagen, TRAP-6 and
      arachidonic acid. Moreover, G4-Arginine-Tos present inhibition of platelet
      secretion and thrombus formation under flow conditions. Based on our study, the
      PAMAM G4-Arginine-Tos derivative is hemocompatible and produces desirable
      antiplatelet and antithrombotic effects. Thus, this compound has potential
      applications as an antithrombotic drug or a drug delivery vehicle.

PMID- 24095754
TI  - The development of bis(hydroxymethyl)pyrrole analogs as bifunctional DNA cross
      linking agents and their chemotherapeutic potential.
AB  - Bifunctional DNA cross-linking agents are widely used as chemotherapeutic agents
      in clinics. The advance in the development of these agents as potential antitumor
      agents has generated various types of bis(hydroxymethyl)pyrrole analogs. In order
      to develop highly effective anticancer agents, it is necessary to understand the
      chemophysical properties, structure-activity relationships, therapeutic potency,
      toxicity/safety, and pharmacokinetics of these DNA cross-linking agents. This
      review presents an overview of the recent advances in developing various types of
      bis(hydroxymethyl)pyrrole analogs with potential antitumor activity to provide
      more information for future drug design and strategies for combination
      chemotherapy. The rational drug design, chemical syntheses, antitumor activity,
      mechanism of action, and development of combined chemotherapy regimens, including
      a DNA repair inhibitor, are discussed. 

PMID- 24095755
TI  - Design, synthesis and biological activities of some 7-aminocephalosporanic acid
      derivatives.
AB  - The treatment of 7-ACA with 4-substituted benzensulfonyl chlorides afforded the
      compounds containing 4-nitro/aminophenyl sulfonylamino moiety in the
      cephalosporanic acid skeleton (2, 4). The synthesis of the cephalosporanic acid
      derivatives containing 1,3-thiazole or 5-oxo-1,3-thiazolidine nucleus and
      sulfonamide function (8a, 8b, 10) was performed starting from 7-ACA by several
      steps. The reaction of 7-ACA with [4-(2-fluoro-4-nitrophenyl)piperazin-1
      yl]acetyl chloride afforded the corresponding 7-{[4-(2-fluoro-4
      nitrophenyl)piperazin-1-yl]acetyl}amino derivative (13). The synthesized
      compounds were screened for their antimicrobial and antiurease activities. Some
      of them were found to possess good-moderate antimicrobial activity against the
      test microorganisms. Compound 5d was observed to have moderate anti-urease
      activity. 

PMID- 24095756
TI  - Multifunctional tacrine-flavonoid hybrids with cholinergic, beta-amyloid
      reducing, and metal chelating properties for the treatment of Alzheimer's
      disease.
AB  - A new series of tacrine-flavonoid hybrids (13a-u) had been designed, synthesized,
      and evaluated as multifunctional cholinesterase (ChE) inhibitors against
      Alzheimer's disease (AD). In vitro studies showed that most of the molecules
      exhibited a significant ability to inhibit ChE and self-induced amyloid-beta
      (Abeta1-42) aggregation. Kinetic and molecular modeling studies also indicated
      compounds were mixed-type inhibitors, binding simultaneously to active,
      peripheral and mid-gorge sites of AChE. Particularly, compound 13k was found to
      be highly potent and showed a balanced inhibitory profile against ChE and self
      induced Abeta1-42 aggregation. Moreover, it also showed excellent metal chelating
      property and low cell toxicity. These results suggested that 13k might be an
      excellent multifunctional agent for AD treatment.

PMID- 24095757
TI  - Design, syntheses, and characterization of pharmacophore based chemokine receptor
      CCR5 antagonists as anti prostate cancer agents.
AB  - Accumulating evidence has shown multiple roles that chemokine receptor CCR5 may
      play to promote the progression of several types of cancer. The mechanism of such
      promotion is believed to involve chronic inflammation that creates a
      microenvironment which enhances tumor survival. Therefore, blocking CCR5 function
      with an antagonist may provide a novel treatment of cancers such as prostate
      cancer. Currently, several CCR5 antagonists are available, but all have been
      optimized for their inhibitory activity on HIV-1 cellular membrane invasion
      process rather than inhibition on cytoplasmic signaling pathways. Thus, there is
      need to develop CCR5 antagonists focusing on blockage of CCR5 downstream
      signaling and inhibition of CCR5 related prostate cancer proliferation and
      progression. In this report, a pharmacophore analysis was conducted based on
      docking studies of several known CCR5 antagonists in a CCR5 homology model. A
      unique structural skeleton for CCR5 antagonist was constructed and
      functionalized, resulting in a new series of small molecules to be synthesized
      and characterized. A combination of CCR5 calcium flux inhibition, anti prostate
      cancer cell proliferation, basal cytotoxicity, and in vivo animal model studies
      were applied to screen the newly synthesized compounds. Results from this study
      provided a potential lead compound for future CCR5 antagonist development
      focusing on prostate cancer therapy.

PMID- 24095758
TI  - Isoxazole derivatives as potent transient receptor potential melastatin type 8
      (TRPM8) agonists.
AB  - Modulation of the transient receptor potential melastatin type-8 (TRPM8), the
      receptor for menthol acting as the major sensor for peripheral innocuous cool
      temperatures, has several important applications in pharmaceutical, food and
      cosmetic industries. In the present study, we designed 12 isoxazole derivatives
      and tested their pharmacological properties both in F11 sensory neurons in vitro,
      and in an in vivo model of cold allodynia. In F11 sensory neurons, single-cell
      Ca(2+)-imaging experiments revealed that, when compared to menthol, some newly
      synthesized compounds were up to 200-fold more potent, though none of them showed
      an increased efficacy. Some isoxazole derivatives potentiated allodynic responses
      elicited by acetone when administered to rats subjected to sciatic nerve
      ligation; when compared to menthol, these compounds were efficacious at earlier
      (0-2 min) but not later (7-9 or 14-16 min) time points. Docking experiments
      performed in a human TRPM8 receptor model revealed that newly-synthesized
      compounds might adopt two possible conformations, thereby allowing to distinguish
      "menthol-like" compounds (characterized by high efficacy/low potency), and
      "icillin-like" compounds (with high potency/low efficacy). Collectively, these
      data provide rationale structure-activity relationships for isoxazole derivatives
      acting as TRPM8 agonists, and suggest their potential usefulness for cold-evoked
      analgesia.

PMID- 24095759
TI  - New synthetic aliphatic sulfonamido-quaternary ammonium salts as anticancer
      chemotherapeutic agents.
AB  - RhoB is expressed during tumor cell proliferation, survival, invasion, and
      metastasis. In malignant progression, the expression levels of RhoB are commonly
      attenuated. RhoB is known to be linked to the regulation of the PI3K/Akt survival
      pathways. Based on aliphatic amido-quaternary ammonium salts that induce
      apoptosis via up-regulation of RhoB, we synthesized novel aliphatic sulfonamido
      quaternary ammonium salts. These new synthetic compounds were evaluated for their
      biological activities using an in vitro RhoB promoter assay in HeLa cells, and in
      a growth inhibition assay using human cancer cell lines including PC-3, NUGC-3,
      MDA-MB-231, ACHN, HCT-15, and NCI-H23. Compound 5b (ethyl-dimethyl-{3-[methyl
      (tetradecane-1-sulfonyl)-amino]-propyl}-ammonium; iodide) was the most promising
      anticancer agent in the series, based upon the potency of growth inhibition and
      RhoB promotion. These new aliphatic sulfonamido-quaternary ammonium salts could
      be a valuable series for development of new anticancer chemotherapeutic agents.

PMID- 24095760
TI  - Synthesis of quinoidal molecules: strategies towards bioactive compounds with an
      emphasis on lapachones.
AB  - Naphthoquinoidal compounds are of great interest in medicinal chemistry. In
      recent years, several synthetic routes have been developed to obtain bioactive
      molecules derived from lapachones. In this mini-review, we focus on the synthetic
      aspects and strategies used to design these compounds and on the biological
      activities of these substances for the development of drugs against the neglected
      diseases leishmaniasis and Chagas disease as well as malaria, tuberculosis and
      cancer. Three strategies used to develop bioactive naphthoquinoidal compounds are
      discussed: (i) C-ring modification, (ii) redox centre modification and (iii) A
      ring modification. Among these strategies, reactions such as copper-catalysed
      azide-alkyne cycloaddition (click chemistry), palladium-catalysed cross
      couplings, and heterocyclisations will be discussed for the development of
      naphthoquinoidal compounds against Trypanosoma cruzi, Leishmania and cancer. The
      aim of derivatisation is the generation of novel molecules that inhibit cellular
      organelles/processes, generate reactive oxygen species (ROS) and increase
      lipophilicity to enhance penetration through the plasma membrane. Modified
      lapachones have emerged as promising prototypes for the development of drugs
      against neglected diseases and cancer. 

PMID- 24095761
TI  - Carbonic anhydrase inhibitors. Synthesis of heterocyclic 4-substituted pyridine-3
      sulfonamide derivatives and their inhibition of the human cytosolic isozymes I
      and II and transmembrane tumor-associated isozymes IX and XII.
AB  - A series of novel heterocyclic 4-substituted pyridine-3-sulfonamides 2-13, 15-20
      have been synthesized and investigated as inhibitors of four isoforms of zinc
      enzyme carbonic anhydrase (CA.EC 4.2.1.1), that is the cytosolic CA I and II, and
      tumor-associated isozymes CA IX and XII. Against the human isozymes hCA I the new
      compounds showed K(I) values in the range 169-5400 nM, toward hCA II in range
      58.5-1238 nM, against hCA IX in range 19.5-652 nM and against hCA XII in the
      range of 16.8-768 nM. Compounds 15-19 representing 4-(1H-pyrazol-1-yl)-3
      pyridinesulfonamide derivatives showed good hCA IX inhibitory efficacy with K(I)
      = 19.5-48.6 nM comparable or more effective than clinically used sulfonamides:
      AAZ, MZA, EZA, DCP, IND (K(I) = 24-50 nM). Anticancer evaluation at a single dose
      10 MUM, against a panel of 60 human tumor cell lines, was performed at the US
      National Cancer Institute, on compounds 2, 3, 5-13, 16, 17, 19, 20. Among them 6
      bearing 4-(3,4,-dichlorophenyl)piperazine moiety showed broad spectrum of growth
      inhibition in the range 25-89% over 26 cell lines representing all tumors
      subpanels.

PMID- 24095762
TI  - Design and application of a rigid quinazolone scaffold based on two-face Bim
      alpha-helix mimicking.
AB  - Based on our previous discovery of an anthraquinone scaffold mimicking two faces
      of Bim alpha-helix, we derived a quinazolone scaffold through structure
      simplification and optimization. It was inferred that a rigid bicyclic ring was
      necessary and efficient to maintain the two-faced binding mode. A novel dual
      inhibitor 6c [6,7,8-trihydroxy-3-(2-hydroxy-5-methylbenzyl)-2-phenylquinazolin
      4(3H)-one] was obtained based on this scaffold. 6c exhibited dual binding
      activity with K(i) values of 0.123 MUM for Mcl-1 and 0.179 MUM for Bcl-2.

PMID- 24095763
TI  - cis-Dichloroplatinum(II) complexes tethered to dibenzo[c,h][1,6]naphthyridin-6
      ones: synthesis and cytotoxicity in human cancer cell lines in vitro.
AB  - A novel family of cisplatin-type complexes tethered to
      dibenzo[c,h][1,6]naphthyridin-6-one topoisomerase inhibitor via a polymethylene
      chain and their nonplatinated counterparts were prepared. Their potential
      cytotoxicity was assessed in three human colorectal cancer cell lines HCT 116,
      SW480 and HT-29 and compared to the reference molecules cisplatin and
      oxaliplatin. Platinated compounds were poorly active whilst nonplatinated
      dibenzo[c,h][1,6]naphthyridin-6-one moieties exhibited higher cytotoxic
      properties than cisplatin and oxaliplatin whatever the length of the
      polymethylene chain; molecules containing the tri- and hexamethylene chain length
      were the most cytotoxic. 

PMID- 24095764
TI  - New orally effective 3-(2-nitro)phenylpropanamide analgesic derivatives:
      synthesis and antinociceptive evaluation.
AB  - A series of substituted 6-nitrophenylpropanamide derivatives (1-20) were
      synthesized using either the TDAE strategy or classical organic reactions. All
      these compounds were characterized by fusion point, (1)H NMR, (13)C NMR,
      elemental analysis or mass spectrometry data. Because of their structural analogy
      with recently published compounds possessing antinociceptive properties, our
      derivatives were screened for peripheral analgesic activities on acetic acid
      induced writhing in mice. Compound 13 showed the best result at 100 MUmol/kg ip
      (50% inhibition vs 59% for aspirin). This antinociceptive activity was maintained
      after oral administration (40% inhibition vs 31.6% for aspirin). Both hot-plate
      and actimetry-based tests were non-significant suggesting the analgesic activity
      of 13 linked to a peripheral mechanism.

PMID- 24095765
TI  - Diagnostic utility of isoelectric focusing and high performance liquid
      chromatography in neonatal cord blood screening for thalassemia and non-sickling
      hemoglobinopathies.
AB  - BACKGROUND: Thalassemia syndromes are highly prevalent in Southeast Asia. In
      Thailand, high performance liquid chromatography (HPLC) is the most common
      technique routinely performed in diagnosis of thalassemia and hemoglobinopathies,
      while isoelectric focusing (IEF) is rarely employed. We compared the diagnostic
      utility of IEF and HPLC in neonatal screening for thalassemia and non-sickling
      hemoglobinopathies. METHODS: Two-hundred and forty-one cord blood samples were
      analyzed using IEF and HPLC, beta-thalassemia short program. The results were
      correlated with red cell indices and molecular analyses. Hemoglobin (Hb) Bart's
      was quantified only on IEF. RESULTS: Of 241 newborns, IEF and HPLC yielded 85.4%
      and 76.4% sensitivity to identify alpha-thalassemia syndrome, respectively.
      HbBart's>=2% yielded 100% sensitivity to identify 2 alpha-globin gene deletions
      and/or mutations, while MCV<=95fl and MCH<=30pg yielded 100% sensitivity to
      identify 2 alpha-globin gene deletions. DNA analysis revealed HbE mutation in all
      61 subjects with HbA2>1% on both IEF and HPLC. CONCLUSION: IEF is an effective
      method in neonatal screening for thalassemia and non-sickling hemoglobinopathies.
      The HbBart's level, MCV and MCH are helpful for identifying alpha-thalassemia.
      The presence of HbA2 higher than 1% in cord blood indicates HbE carriers in
      Southeast Asian newborns.

PMID- 24095766
TI  - Insights into the fish thioredoxin system: expression profile of thioredoxin and
      thioredoxin reductase in rainbow trout (Oncorhynchus mykiss) during infection and
      in vitro stimulation.
AB  - Production of reactive oxygen species (ROS) is the first biological response
      during a disease outbreak and after injury. ROS are highly reactive molecules
      that can either endanger cell homeostasis or mediate cell signaling in several
      physiological pathways, including the immune response. Thioredoxin (Trx) and
      thioredoxin reductase (TrxR) are the essential components of the thioredoxin
      system, one of the main intracellular redox systems and are therefore important
      regulators of ROS accumulation. Through the regulation of the intracellular redox
      milieu, the thioredoxin system plays a key role within the immune system, linking
      immunology and free radical science. In this study we have firstly identified
      TrxRs in fish and used this new sequence information to reevaluate the evolution
      of the thioredoxin system within the vertebrate lineage. We next measured the
      expression of rainbow trout (Oncorhynchus mykiss) Trx and TrxR transcripts during
      infection in vivo and in vitro after stimulation of a macrophage cell line and
      primary macrophage cultures with pathogen associated molecular patterns (PAMPs).
      Our results showed that both Trx and TrxR were induced during infection at the
      transcriptional level, confirming their likely involvement in the innate immune
      response of fish. Since TrxRs are selenium-containing proteins (selenoproteins),
      we also measured the modulation of their expression upon organic and inorganic
      selenium exposure in vitro. TrxR was found to be responsive to selenium exposure
      in vitro, suggesting that it may represent a key mediator in the selenium
      modulation of innate immunity. In conclusion, our study highlights the need to
      investigate the involvement of the cell antioxidant pathways, especially the
      thioredoxin system, within the immune system of vertebrate species.

PMID- 24095767
TI  - Transmissible gastroenteritis virus infection induces cell cycle arrest at S and
      G2/M phases via p53-dependent pathway.
AB  - p53 signaling pathway plays an important role in the regulation of cell cycle.
      Our previous studies have demonstrated that TGEV infection induces the activation
      of p53 signaling pathway. In this study we investigated the effects of TGEV
      infection on the cell cycle of host cells and the roles of p53 activation in this
      process. The results showed that TGEV infection induced cell cycle arrest at S
      and G2/M phases in both asynchronous and synchronized PK-15 and ST cells, while
      UV-inactivated TGEV lost the ability of induction of cell cycle arrest. TGEV
      infection promoted p21 accumulation, down-regulated cell cycle-regulatory
      proteins cyclins B1, cdc2, cdk2 and PCNA. Further studies showed that inhibition
      of p53 signaling could attenuate the TGEV-induced S- and G2/M-phase arrest by
      reversing the expression of p21 and corresponding cyclin/cdk. In addition, TGEV
      infection of the cells synchronized in various stages of cell cycle showed that
      viral genomic RNA and subgenomic RNA, and virus titer were higher in the cells
      released from S-phase- or G2/M phase-synchronized cells than that in the cells
      released from the G0/G1 phase-synchronized or asynchronous cells after 18h p.i.
      Taken together, our data suggested that TGEV infection induced S and G2/M phase
      arrest in host cells, which might provide a favorable condition for viral
      replication. 

PMID- 24095768
TI  - Normal coordinate analysis, molecular structure, vibrational and electronic
      spectral investigation of 7-(1,3-dioxolan-2-ylmethyl)-1,3-dimethylpurine-2,6
      dione by ab initio HF and DFT method.
AB  - In the present work, the characterization of 7-(1,3-dioxolan-2-ylmethyl)-1,3
      dimethylpurine-2,6-dione (7DDMP26D) molecule was carried out by quantum chemical
      method and vibrational spectral techniques. The FT-IR (4000-400 cm(-1)) and FT
      Raman (4000-100 cm(-1)) spectra of 7DDMP26D were recorded in solid phase. The UV
      Vis absorption spectrum of the 7DDMP26D was recorded in the range of 200-400 nm.
      The molecular geometry, harmonic vibrational frequencies and bonding features of
      7DDMP26D in the ground state have been calculated by HF and DFT methods using 6
      31G(d,p) basis set. The complete vibrational frequency assignments were made by
      normal coordinate analysis (NCA) following the scaled quantum mechanical force
      field methodology (SQMF). The molecular stability and bond strength were
      investigated by applying the natural bond orbital analysis (NBO). The electronic
      properties, such as excitation energies, absorption wavelength, HOMO and LUMO
      energies were performed by time-depended DFT (TD-DFT) approach. The other
      molecular properties like electrostatic potential (ESP), Fukui function and
      thermodynamic properties of the title compound at different temperatures have
      been calculated. Finally, the calculation results were analyzed to simulate
      infrared, FT-Raman and UV spectra of the title compound which shows better
      agreement with observed spectra.

PMID- 24095769
TI  - Novel banana peel pectin mediated green route for the synthesis of hydroxyapatite
      nanoparticles and their spectral characterization.
AB  - Hydroxyapatite [HAP, Ca10(PO4)6(OH)2] is the main inorganic component of natural
      bone and is widely used in various biomedical applications. In this paper, we
      have reported the synthesis of HAP nanoparticles by banana peel pectin mediated
      green template method. The pectin extracted from the peels of banana and its
      various concentrations were exploited in our study to achieve a controlled
      crystallinity, particle size as well as uniform morphology of HAP. The extracted
      pectin was characterized by spectral techniques like Fourier transform infrared
      spectroscopy (FTIR) for the functional group analysis, proton-1 nuclear magnetic
      resonance spectroscopy ((1)H NMR) and carbon-13 nuclear magnetic resonance
      spectroscopy ((13)C NMR) for the identification of H and C atoms in the extracted
      pectin, respectively. The HAP nanoparticles were synthesized using different
      concentrations of the as-extracted pectin. The purity, crystallinity and
      morphology of the as-synthesized HAP nanoparticles were evaluated by FTIR, X-ray
      diffraction (XRD) and scanning electron microscopy (SEM) with energy dispersive X
      ray analysis (EDAX) and transmission electron microscopy (TEM), respectively.
      Moreover the antibacterial activity of HAP nanoparticles was evaluated against
      the gram positive and negative bacteria like Staphylococcus aureus (S. aureus)
      and Escherichia coli (E. coli), respectively. The experimental results revealed
      that the HAP nanoparticles synthesized in the presence of an optimized
      concentration of pectin are pure, low crystalline, spherical and discrete
      particles with reduced size. Also, the HAP sample derived in the presence of
      pectin showed an enhanced antibacterial activity than that of the HAP synthesized
      in the absence of pectin. Hence, the HAP nanoparticles synthesized using pectin
      as a green template can act as a good biomaterial for biomedical applications. 

PMID- 24095770
TI  - An analytical Raman spectroscopic study of an important english oil painting of
      the 18th Century.
AB  - An opportunity was afforded to analyse pigment specimens from an unrestored oil
      painting in the style of the English School of the mid-18th Century prior to
      conservation being undertaken. Raman spectroscopy was adopted to characterise the
      pigments and indicated the presence of a novel red pigment which was assigned to
      the complex chromium mineral, hemihedrite, in addition to other interesting
      materials found in combination. This is the first recorded identification of
      hemihedrite spectral signals in an art context in a range of mineral pigments
      that are otherwise typical of this period and some hypotheses are presented to
      explain its presence based on its occurrence with associated mineral pigments. It
      is suggested that the presence of powdered glass identified in certain areas of
      the painting enhanced the reflectivity of the pigment matrix. 

PMID- 24095771
TI  - Influence of Li+ codoping on visible emission of Y2O3:Tb3+, Yb3+ phosphor.
AB  - Upon 980 nm diode laser excitation visible upconversion emission from the Tb(3+)
      ions has been observed in combustion synthesized Tb(3+)-Yb(3+) codoped Y2O3
      phosphor. The intensity of upconversion as well as downconversion emission bands
      has been increased by codoping of Li(+) ions into Tb(3+)-Yb(3+):Y2O3 phosphor and
      the reason behind this increment is discussed. The pump power dependence of
      upconversion emission bands has shown two-photon absorption process. The
      cooperative energy transfer from Yb(3+) to Tb(3+) ions is supposed to be
      responsible for the upconversion emission from the Tb(3+) ions on near infrared
      excitation. The calculated colour coordinates indicate the purity of intense
      green emission from present phosphor which is suitable for various photonic
      applications.

PMID- 24095772
TI  - Synthesis, characterization, electrochemical and biological studies on some
      metal(II) Schiff base complexes containing quinoxaline moiety.
AB  - Novel Co(II), Ni(II), Cu(II) and Zn(II) complexes of Schiff base derived from
      quinoxaline-2,3-(1,4H)-dione and 4-aminoantipyrine (QDAAP) were synthesized. The
      ligand and its complexes were characterized by elemental analyses, molar
      conductance, magnetic susceptibility measurements, FTIR, UV-Vis., mass and (1)H
      NMR spectral studies. The X band ESR spectrum of the Cu(II) complex at 300 and
      77K were also recorded. Thermal studies of the ligand and its complexes show the
      presence of coordinated water in the Ni(II) and Zn(II) complexes. The
      coordination behavior of QDAAP is also discussed. All the complexes are mono
      nuclear and tetrahedral geometry was found for Co(II) complex. For the Ni(II) and
      Zn(II) complexes, octahedral geometry was assigned and for the Cu(II) complex,
      square planar geometry has been suggested. The grain size of the complexes was
      estimated using powder XRD. The surface morphology of the compounds was studied
      using SEM analysis. Electrochemical behavior of the synthesized complexes in DMF
      at room temperature was investigated by cyclic voltammetry. The in vitro
      biological screening of QDAAP and its metal complexes were tested against
      bacterial species Staphylococcus aureus, Escherichia coli and Pseudomonas
      aeruginosa. The fungal species include Aspergillus niger, Aspergillus flavus and
      Candida albicans. The DNA cleavage activity of QDAAP and its complexes were also
      discussed. 

PMID- 24095773
TI  - [The announcement of the diagnosis of cancer: point of view of the general
      practitioner].
AB  - The announcement of the diagnosis of cancer is difficult for doctors and patients
      alike. The main objective is the study of announcement's techniques used by
      physicians to send their patients in cancer centers. The second objective is to
      analyze encountered difficulties and experience of the announcement of the
      diagnosis. The final objective would be to provide practical ideas for GPs for a
      better communication with their patients in this announcement. We have conducted
      a qualitative study by interviewing fifteen GPs. The fifteen semi-structured
      interviews have been recorded and transcribed verbatim. A first analysis has been
      done manually to achieve a set of nodes and then in a second time using N Vivo
      Software 9. Most of the GPs break the news of cancer with or without pathology.
      They know the basics of patient-physician communication to promote the patient's
      expression. Some doctors have a positive experience and claim their role in this
      announcement. Their negative experience is linked to representations made about
      the disease and generated feeling. The results of this study show a need of
      training for physicians in order to acquire know-how and attitude at the time of
      cancer announcement. 

PMID- 24095774
TI  - The mitochondrial genome of the Russian wheat aphid Diuraphis noxia: large
      repetitive sequences between trnE and trnF in aphids.
AB  - To characterize aphid mitochondrial genome (mitogenome) features, we sequenced
      the complete mitogenome of the Russian wheat aphid, Diuraphis noxia. The 15,784
      bp mitogenome with a high A+T content (84.76%) and strong C skew (-0.26) was
      arranged in the same gene order as that of the ancestral insect. Unlike typical
      insect mitogenomes, D. noxia possessed a large tandem repeat region (644 bp)
      located between trnE and trnF. Sequencing partial mitogenome of the cotton aphid
      (Aphis gossypii) further confirmed the presence of the large repeat region in
      aphids, but with different repeat length and copy number. Another motif (58 bp)
      tandemly repeated 2.3 times in the control region of D. noxia. All repeat units
      in D. noxia could be folded into stem-loop secondary structures, which could
      further promote an increase in copy numbers. Characterization of the D. noxia
      mitogenome revealed distinct mitogenome architectures, thus advancing our
      understanding of insect mitogenomic diversities and evolution.

PMID- 24095775
TI  - Molecular characterisation of TNF, AIF, dermatopontin and VAMP genes of the flat
      oyster Ostrea edulis and analysis of their modulation by diseases.
AB  - Bonamiosis and disseminated neoplasia (DN) are the most important diseases
      affecting cultured flat oysters (Ostrea edulis) in Galicia (NW Spain). Previous
      research of the response of O. edulis against bonamiosis by suppression
      subtractive hybridisation yielded a partial expressed sequence tag of tumour
      necrosis factor (TNF) and allograft inflammatory factor (AIF), as well as the
      whole open reading frame for dermatopontin and vesicle-associated membrane
      (VAMP). Herein, the complete open reading frames of TNF and AIF genes were
      determined by the rapid amplification of cDNA, and the deduced amino acid
      sequences of the four genes were characterised. Phylogenetic relationships for
      each gene were studied using maximum likelihood parameters. Quantitative-PCR
      assays were also performed in order to analyse the modulation of the expression
      of these genes by bonamiosis and disseminated neoplasia. Gene expression profiles
      were studied in haemolymph cells and in various organs (gill, gonad, mantle and
      digestive gland) of oysters affected by bonamiosis, DN, and both diseases with
      regard to non-affected oysters (control). TNF expression in haemolymph cells was
      up-regulated at heavy stage of bonamiosis but its expression was not affected by
      DN. AIF expression was up-regulated at heavy stage of bonamiosis in haemolymph
      cells and mantle, which is associated with heavy inflammatory response, and in
      haemolymph cells of oysters affected by DN. AIF expression was, however, down
      regulated in other organs as gills and gonads. Dermatopontin expression was down
      regulated in haemolymph cells and digestive gland of oysters affected by
      bonamiosis, but DN had no significant effect on its expression. Gills and gonads
      showed up-regulation of dermatopontin expression associated with bonamiosis.
      There were significant differences in the expression of TNF and VAMP depending on
      the bonamiosis intensity stage whereas no significant differences were detected
      between light and heavy severity degrees of DN for the studied genes. VAMP
      expression showed also differences among haemolymph cells and the organs studied.
      The occurrence of both diseases in oysters involved haemolymph cell gene
      expression patterns different from those associated to each disease separately:
      no significant effect was observed in TNF expression, dermatopontin was up
      regulated and marked up-regulation of AIF and VAMP was recorded, which suggests a
      multiplier effect of the combination of both diseases for the latter two genes.

PMID- 24095776
TI  - Siblings with opposite chromosome constitutions, dup(2q)/del(7q) and
      del(2q)/dup(7q).
AB  - Chromosome 7q36 microdeletion syndrome is a rare genomic disorder characterized
      by underdevelopment of the brain, microcephaly, anomalies of the sex organs, and
      language problems. Developmental delay, intellectual disability, autistic
      spectrum disorders, BDMR syndrome, and unusual facial morphology are the key
      features of the chromosome 2q37 microdeletion syndrome. A genetic screening for
      two brothers with global developmental delay using high-resolution chromosomal
      analysis and subtelomeric multiplex ligation-dependent probe amplification
      revealed subtelomeric rearrangements on the same sites of 2q37.2 and 7q35, with
      reversed deletion and duplication. Both of them showed dysmorphic facial
      features, severe disability of physical and intellectual development, and
      abnormal genitalia with differential abnormalities in their phenotypes. The
      family did not have abnormal genetic phenotypes. According to the genetic
      analysis of their parents, adjacent-1 segregation from their mother's was
      suggested as a mechanism of their gene mutation. By comparing the phenotypes of
      our patients with previous reports on similar patients, we tried to obtain the
      information of related genes and their chromosomal locations. 

PMID- 24095777
TI  - Molecular evolution of the HD-ZIP I gene family in legume genomes.
AB  - Homeodomain leucine zipper I (HD-ZIP I) genes were used to increase the
      plasticity of plants by mediating external signals and regulating growth in
      response to environmental conditions. The way genomic histories drove the
      evolution of the HD-ZIP I family in legume species was described; HD-ZIP I genes
      were searched in Lotus japonicus, Medicago truncatula, Cajanus cajan and
      Phaseolus vulgaris, and then divided into five clades through phylogenetic
      analysis. Microsynteny analysis was made based on genomic segments containing the
      HD-ZIP I genes. Some pairs turned out to conform with syntenic genome regions,
      while others corresponded to those that were inverted, expanded, or contracted
      after the divergence of legumes. Besides, we dated their duplications by Ks
      analysis and demonstrated that all the blocks were formed after the monocot-dicot
      split; we observed Ka/Ks ratios representing strong purifying selections in the
      four legume species which might have been followed by gene loss and
      rearrangement. 

PMID- 24095778
TI  - Characterization, expression and localization of valosin-containing protein in
      ovaries of the giant tiger shrimp Penaeus monodon.
AB  - Valosin-containing protein (VCP), a member of the ATPase-associated with diverse
      cellular activity (AAA) family, was identified from the giant tiger shrimp
      (Penaeus monodon). The full-length cDNA of the PmVCP mRNA consisted of 2,724 bp
      containing an ORF of 2,367 bp corresponding to a deduced polypeptide of 788 amino
      acids. The deduced PmVCP protein contained two putative Cdc48 domains (positions
      17-103, E-value=2.00e-36 and 120-186, E-value=3.60e-11) and two putative AAA
      domains (positions 232-368, E-value=3.67e-24 and 505-644, E-value=3.73e-25).
      PmVCP mRNA expression in ovaries was greater than that in testes in both
      juveniles and broodstock. PmVCP was significantly up-regulated in stages II and
      IV ovaries in intact wild broodstock (P<0.05) but it was not differentially
      expressed during ovarian development in eyestalk-ablated broodstock (P>0.05). The
      expression level of PmVCP mRNA in ovaries of 14-month-old shrimp was not affected
      by progesterone injection (0.1MUg/g body weight, P>0.05). In contrast, exogenous
      5-HT administration (50MUg/g body weight) resulted in an increase of PmVCP mRNA
      in ovaries of 18-month-old shrimp at 6 and 24h post-injection (hpi) (P<0.05). The
      rPmCdc48-VCP protein and its polyclonal antibody were successfully produced.
      Cellular localization revealed that PmVCP was localized in the ooplasm of
      previtellogenic oocytes. Subsequently, it was translocated into the germinal
      vesicle of vitellogenic oocytes. Interestingly, PmVCP was found in nucleo
      cytoplasmic compartments, in the cytoskeletal architecture and in the plasma
      membrane of mature oocytes in both intact and eyestalk-ablated broodstock.

PMID- 24095779
TI  - Inactivation of the integrin-linked kinase (ILK) in osteoblasts increases
      mineralization.
AB  - In osteoblasts, Integrin-Linked Kinase (ILK)-dependent phosphorylation of the
      cJUN transcriptional coactivator, alphaNAC, induces the nuclear accumulation of
      the coactivator and potentiates cJUN-dependent transcription. Mutation of the ILK
      phosphoacceptor site within the alphaNAC protein leads to cytoplasmic retention
      of the coactivator and cell-autonomous increases in osteoblastic activity. In
      order to gain further insight into the ILK-alphaNAC signaling cascade, we
      inactivated ILK using RNA knockdown in osteoblastic cells and engineered mice
      with specific ablation of ILK in osteoblasts. ILK knockdown in MC3T3-E1
      osteoblast-like cells reduced phosphorylation of its downstream target glycogen
      synthase kinase 3beta (GSK3beta), which led to cytoplasmic retention of alphaNAC
      and increased mineralization with augmented expression of the osteoblastic
      differentiation markers, pro-alpha1(I) collagen (col1A1), Bone Sialoprotein (Bsp)
      and Osteocalcin (Ocn). Cultured ILK-deficient primary osteoblasts also showed
      increased cytoplasmic alphaNAC levels, and augmented mineralization with higher
      Runx2, Col1a1 and Bsp expression. Histomorphometric analysis of bones from mutant
      mice with ILK-deficient osteoblasts (Col1-Cre;Ilk(-/fl)) revealed transient
      changes, with increased bone volume in newborn animals that was corrected by two
      weeks of age. Our data suggest that the ILK-alphaNAC cascade acts to reduce the
      pace of osteoblast maturation. We propose that in vivo, functional redundancy is
      able to compensate for the loss of ILK activity, leading to the absence of an
      obvious phenotype when osteoblast-specific Ilk-deficient mice reach puberty.

PMID- 24095780
TI  - Post-zygotic breakage of a dicentric chromosome results in mosaicism for a
      telocentric 9p marker chromosome in a boy with developmental delay.
AB  - Chromosomal rearrangements resulting in an inverted duplication and a terminal
      deletion (inv dup del) can occur due to three known mechanisms, two of them
      resulting in a normal copy region between the duplicated regions. These
      mechanisms involve the formation of a dicentric chromosome, which undergo
      breakage during cell division resulting in cells with either an inverted
      duplication and deletion or a terminal deletion. We describe a mosaic 3 year old
      patient with two cell lines carrying a chromosome 9p deletion where one of the
      cell lines contains an additional telocentric marker chromosome. Our patient is
      mosaic for the product of a double breakage of a dicentric chromosome including a
      centric fission. Mosaicism involving different rearrangements of the same
      chromosome is rare and suggests an early mitotic breakage event. Chr9p terminal
      deletions associated with duplications have previously been reported in 11
      patients. We compare the clinical features of all 12 patients including the
      patient that we report here. To the best to our knowledge this is a first case
      reported where the double breakage occurred in the dicentric derivative
      chromosome 9.

PMID- 24095781
TI  - In vitro studies on release and skin permeation of nonivamide from novel oil-in
      oil-emulsions.
AB  - The purpose of this study was to develop oil-in-oil-emulsions that facilitate
      long-term treatment for chronic pruritus with capsaicinoids. To this end, oil-in
      oil-emulsions, which comprised polydimethyl siloxanes, silicone surfactant and
      castor oil, were examined. We used nonivamide, a synthetic analogue of capsaicin
      as the active pharmaceutical ingredient. It was incorporated into castor oil that
      formed the dispersed phase of the emulsion. We evaluated the influence of
      formulation variables (nonivamide content, phase volume ratio and viscosity of
      the silicone oil) on the in vitro release and the permeation of nonivamide.
      Permeation was found to be controlled by the nonivamide concentration in the
      dispersed phase and the phase volume ratio. Oil-in-oil-emulsions were found to
      produce constant permeation rates over a period of 10h. They are thus superior to
      conventional semisolid formulations as application intervals may be extended. 

PMID- 24095782
TI  - Biocompatibility of silver nanoparticles and silver ions in primary human
      mesenchymal stem cells and osteoblasts.
AB  - The prevention of implant-related infections is an important issue in medical
      research. The aim is to exploit the strong antimicrobial effect of silver
      nanoparticles (AgNP) to develop new antibacterial coatings for implants. However,
      there is still a serious lack of information on the influence of AgNP on bone
      metabolism. In the present study we have evaluated the influence of AgNP on cell
      stress, viability, proliferation and differentiation of primary human mesenchymal
      stem cells (MSC) and osteoblasts (OB). Finally, cellular uptake of the AgNP was
      examined. After 21 days impairment of cell viability of MSC and OB occurred at a
      concentration of 10 MUg/g of AgNP. Cytotoxicity and inhibition of proliferation
      was highly time and dose dependent. No influence on cell differentiation, but an
      increase in cell stress, was observed. Uptake of AgNP into MSC and OB could be
      confirmed. In summary, these results demonstrate AgNP-mediated cytotoxicity at
      higher concentrations. Therefore, a therapeutical window for the application of
      AgNP in medical products might exist. However, the antibacterial benefits and
      potential health risks of AgNP need to be weighed in further studies.

PMID- 24095783
TI  - Enzymatic pH control for biomimetic deposition of calcium phosphate coatings.
AB  - The current study examines the enzymatic decomposition of urea into carbon
      dioxide and ammonia as a means to increase the pH during biomimetic deposition of
      calcium phosphate (CaP) onto implant surfaces. The kinetics of the enzymatically
      induced pH increase were studied by monitoring pH, calcium concentration and
      conductivity of the aqueous solutions as a function of time, urease concentration
      and initial concentrations of calcium and phosphate ions. Cryogenic transmission
      electron microscopy was used to study the process of homogeneous CaP
      precipitation in solution, whereas CaP deposition on conventional acid-etched
      titanium and micropatterned polystyrene (PS) surfaces was studied using scanning
      electron microscopy. The data presented in this study confirm that the substrate
      enzyme combination urea-urease offers strong control over the rate of pH increase
      by varying the concentrations of precursor salts and urease. Formation of
      biomimetic CaP coatings was shown to proceed via formation of ionic polymeric
      assemblies of prenucleation complexes. The process of deposition and
      corresponding coating morphology was strongly dependent on the concentration of
      calcium, phosphate and urease. Finally, it was shown that the substrate-enzyme
      combination urea-urease allowed for spatial distribution of CaP crystals along
      the grooves of micropatterned PS surfaces at low concentrations of calcium,
      phosphate and urease, stressing the sensitivity of the presented method.

PMID- 24095784
TI  - Photo-assisted recall increases estimates of energy and macronutrient intake in
      adults with intellectual and developmental disabilities.
AB  - Diet assessment of adults with intellectual and developmental disabilities is
      challenging because of their limited cognitive abilities. The objective of this
      study was to examine the feasibility and outcomes of combining photos with 24
      hour dietary recalls for the assessment of energy and macronutrient intakes in
      adults with intellectual and developmental disabilities. Participants used an
      iPad 2 tablet computer (Apple) to take photos of all food and beverages consumed
      before a standard, multiple-pass, 24-hour dietary recall. After the standard 24
      hour diet recall, the photos were reviewed with the participant for clarification
      details (eg, portion size) and differences were recorded. The standard 24-hour
      recall and photo-assisted recall were entered separately into the Nutrition Data
      System for Research for computerized dietary analysis. Sixty-four eating
      occasions were entered from 23 participants (48% female; mean age 26.4+/-9.7
      years). Participants captured photos for 66.5%+/-30.4% of all recorded eating
      occasions. Greater energy intake per eating occasion was reported with the photo
      assisted recalls than the standard recalls (625.6+/-85.7 kcal vs 497.2+/-86.6
      kcal; P=0.002) and a greater intake of grams of fat (P=0.006), protein (P=0.029),
      and carbohydrates (P=0.003). Photo-assisted 24-hour recalls provided a
      significant increase in total calories and macronutrient content compared with a
      standard 24-hour recall and may be a feasible method to enhance dietary
      assessment in adults with intellectual and developmental disabilities. 

PMID- 24095785
TI  - Therapeutic peroral pancreatoscopy: shockwave lithotripsy of pancreatic duct
      stones under direct vision.

PMID- 24095786
TI  - Increased incidence of gastrointestinal cancers among patients with pyogenic
      liver abscess: a population-based cohort study.
AB  - BACKGROUND & AIMS: The relationship between pyogenic liver abscess (PLA) and
      gastrointestinal (GI) cancer was first reported more than 20 years ago, yet
      little is known about this connection. We evaluated this association in a
      population-based, retrospective, cohort study. METHODS: Using Taiwan National
      Health Insurance claims data, we collected data on a cohort of 14,690 patients
      with PLA diagnosed from 2000 to 2007. A reference cohort of 58,760 persons
      without PLA (controls) was selected from the same database, frequency matched by
      age, sex, and index year. Both cohorts were followed up until the end of 2009,
      and incidences of GI cancer were calculated. RESULTS: The incidence of GI cancer
      was 4.30-fold higher among patients with PLA compared with controls (10.8 vs
      2.51/1000 person-years). Site-specific analysis showed that the highest incidence
      of colorectal cancer was among patients with PLA and diabetes mellitus, followed
      by patients with PLA without diabetes and controls with diabetes (9.58, 5.76, and
      1.49/10,000 person-years, respectively). The PLA cohort also had a high risk of
      small intestine cancer (adjusted hazard ratio [aHR], 12.7; 95% confidence
      interval [CI], 5.79-27.7) and biliary tract cancer (aHR, 9.56; 95% CI, 6.68
      13.7). Their risk of pancreatic cancer (aHR, 2.51; 95% CI, 1.68-3.76) was also
      significant. However, patients with PLA did not have an increased risk of gastric
      cancer compared with controls. CONCLUSIONS: In a population-based study, we found
      that the incidence of GI cancer is increased more than 4-fold among patients with
      PLA compared with controls. PLA might therefore be an indicator of GI cancer.
      Patients with PLA had the highest incidence of colorectal cancer, followed by
      cancers of the biliary tract, pancreas, and small intestine.

PMID- 24095787
TI  - Influence of agricultural wastes and a finished compost on the decomposition of
      slaughterhouse waste composts.
AB  - The objective of this study was to evaluate the efficacy of combining
      agricultural wastes or a finished compost (wheat straw, horse manure and bedding,
      sheep manure, and a wheat straw-SHW finished compost) as compost feedstocks with
      cattle slaughterhouse wastes (SHW) on a field-scale. The composts were managed in
      covered bins over 200 days and physico-chemical parameters related to organic
      matter bio-degradation were measured over time. Thermophilic temperatures were
      maintained above 55  degrees C for 12-46 days to meet the Canadian Council of
      Ministers of the Environment (CCME) guidelines for pathogen control. Final C:N
      ratios were highest in a horse manure and bedding:SHW compost at 23:1 but ranged
      from 18.5 to 20.5:1 for the remaining three treatments, representing a wheat
      straw:SHW compost and different combinations of horse manure and bedding, SHW,
      and/or sheep manure. Average reduction in mass of total carbon across all the
      composts in the current study was 54.2%. Maturity tests at the end of the study
      determined that the CO2-C evolution rate in all compost products was less than 1
      mg g(-1) organic matter day(-1) suggesting highly stable final compost products.
      Compost mass reductions all responded as exponential decay functions with R(2)
      values ranging from 0.84 to 0.99 regardless of compost feedstock composition.
      Agricultural by-products and composts are suitable feedstocks for use with SHW to
      generate a stable final product while meeting regulatory parameters to achieve
      conventional pathogen control. 

PMID- 24095788
TI  - Dairy farm impacts of fencing riparian land: pasture production and farm
      productivity.
AB  - Dairy farmers are encouraged to restrict stock access by fencing riparian zones
      to reduce stream pollution and improve biodiversity. Many farmers are reluctant
      to create fenced riparian zones because of the perceived loss of productive
      pasture. Anecdotal reports indicate that pasture production in fenced areas is
      especially valued during summer months when water stress is likely to limit
      pasture growth in other areas of the farm. We measured pasture production,
      botanical composition, soil moisture, and fertility in Riparian (within 20 m of
      the riverbank), Flat (greater than 20 but less than 50 m from the riverbank), and
      Hill (elevated) areas on three commercial dairy farms from October 2006 to
      November 2007 in south eastern Australia. Riparian and Flat areas produced
      significantly more pasture, with on average approximately 25% more dry matter per
      ha grown in these areas compared with Hill paddocks. Percentage ryegrass was 14%
      lower on Hill slopes compared with Riparian and Flat areas and was compensated
      for by only a 5% increase in other grass species. Significant seasonal effects
      were observed with the difference in pasture production between Hill, and
      Riparian and Flat areas most pronounced in summer, due to soil moisture
      limitations on Hill paddocks. To examine potential productivity impacts of this
      lost pasture, we used a questionnaire-based survey to interview the farmers
      regarding their farm and riparian management activities. The additional pasture
      that would have been available if the riverbanks were not fenced to their current
      widths ranged from 6.2 to 27.2 t DM for the 2006/2007 year and would have been
      grown on 0.4-3.4% of their milking area. If this pasture was harvested instead of
      grazed, the farmers could have saved between $2000 and $8000 of their purchased
      fodder costs in that year. By fencing their riparian areas to 20 m for
      biodiversity benefits, between 2.2% and 9.8% of their milking area would be out
      of production amounting to about $16,000 in additional purchased fodder costs. We
      discuss the additional fencing, production, and on-going management costs
      associated with fencing riparian areas, the costs to the environment and the
      enterprise of stock freely accessing waterways, as well as the policy
      implications. 

PMID- 24095789
TI  - Fast detection and quantification of Escherichia coli using the base principle of
      the microbial fuel cell.
AB  - Escherichia coli is an important microbial indicator of fecal contamination,
      making accurate quantitative detection of E. coli a key to ensuring public
      health. In this study, a microbial fuel cell (MFC) was used as a detection unit
      of an E. coli sensor, and specific enzymes expressed in E. coli, such as beta-D
      galactosidase (GAL) and beta-D-glucuronidase (GUS), were exploited as biological
      detection elements. As substrates, 4-aminophenyl-beta-D-galactopyranoside (4
      APGal) were used for GAL detection, whereas 8-hydroxyquinoline glucuronide (8
      HQG) and 4-nitrophenyl beta-D-glucuronide (PNPG) were used for GUS detection.
      Once these substrates were hydrolyzed by GAL or GUS, they became
      electrochemically active products, which were, in turn, oxidized on the anode of
      the MFC reactor. The power output of the MFC reactor increased sharply when E.
      coli in the reactor reached the critical concentration. Accordingly, the time
      required to reach the highest voltage output was recorded as a detection time
      (DT), and a negative linear relationship was established between DT and the
      logarithm of the initial concentration of E. coli in the samples studied. The DTs
      of laboratory samples were 140 min and 560 min for initial concentrations of 1.9
      * 10(7) CFU/mL and 42 CFU/mL at 44.5  degrees C. Moreover, the DTs for GUS assays
      were further shortened by induction with methyl beta-D-glucuronide sodium salt
      (MetGlu). The quantitative relationship between DTs and initial E. coli
      concentrations established from replicate laboratory sample assays allowed
      estimation of the E. coli concentration in environmental samples, but with
      approximately 100 min of lag time. The lag time was also observed with E. coli
      samples that were prepared by starving cells in a laboratory. 

PMID- 24095790
TI  - Assessing and classifying plant-related ecological risk under water management
      scenarios in China's Yellow River Delta Wetlands.
AB  - The Yellow River Delta is one of the most vigorous delta areas in the world. The
      wetlands in this delta are ecologically important due to their hydrologic
      attributes and their role as ecotones between terrestrial and aquatic ecosystems.
      In recent years, the Yellow River Delta Wetlands have gradually shrunk and
      degraded due to inadequate environmental flows. Water managers have attempted to
      balance the needs of the environment with the need to protect water supplies for
      agriculture and urban needs. Despite the need for environmental protection, a
      broad-scale, integrated way to characterize the degree of ecological stress in
      the wetlands has been lacking to date. To provide a framework for evaluating
      various potential water regimes, we developed a model that can be used to
      estimate the ecological risk for wetland plants, and used the model to determine
      the degree of ecological risk for different soil moisture conditions based on an
      ecological value at risk model that we developed and the fuzzy clustering method.
      The results revealed the spatial distribution of areas with high, medium, or low
      risks associated with water stress in the study area. These results can serve as
      a preliminary template to guide managers in their evaluation of water stress
      related risk. 

PMID- 24095791
TI  - Subjective vs. objective measures in the valuation of water quality.
AB  - Environmental valuation studies rely on accurate descriptions of the current
      environmental state and its change. Valuation scenario can be based on objective
      quality measures described to respondents, on individual subjective perceptions
      or their combination. If subjective perceptions differ systematically from
      objective measures, valuation results may be biased. We examine the factors
      underlying the divergence between perceptions of water quality among summer house
      owners and the objective water quality classification. We use bivariate probit
      and multinomial logit models to identify factors that explain both the divergence
      between perceived and objectively measured water quality and its direction,
      paying special attention to variables essential in valuation, including those
      describing the respondent, the summer house and the water body. Some 50% of the
      respondents perceive water quality differently from the objective quality
      measures. Several factors are identified behind systematic differences between
      the perceived and objectively measured quality, in particular the water body
      type, the level of the objective quality classification and the travel distance
      to the site. The results emphasize the need to take individual perceptions into
      account in addition to objective measures in valuation studies, especially if the
      environmental quality of the study area differs considerably from the average
      quality in general. 

PMID- 24095792
TI  - Characterization of Rhinodrilus alatus hemoglobin (HbRa) and its subunits:
      evidence for strong interaction with cationic surfactants DTAB and CTAC.
AB  - Rhinodrilus alatus is an annelid and its giant extracellular hemoglobin (HbRa)
      has a molecular mass (MM) of 3500kDa. In the current study, the characterization
      of MM values of the HbRa subunits, and the effects of surfactants and alkaline pH
      upon HbRa stability were monitored. Electrophoresis, MALDI-TOF-MS and AUC show
      that the MM values of HbRa subunits are very close, but not identical to the
      Glossoscolex paulistus hemoglobin (HbGp). The monomer d is found to exist in, at
      least, two isoforms: the main one, d1, displays a MM of 16,166+/-16Da, and the
      second one, d2, is less intense with MM of 16,490+/-20Da. For the trimer abc and
      tetramer abcd, single contributions around 51,470Da and 67,690Da were observed,
      respectively. Finally, the monomers a, b, and c, present MM values of 17,133,
      17,290 and 15,506Da, respectively. Both CTAC and DTAB interact strongly with
      HbRa, and up to seven surfactant molecules are bound to the protein. On the other
      hand, spectroscopic studies show that HbRa is more stable at alkaline pH, as
      compared to HbGp. Thus, our data suggest that alkaline medium, up to pH10.0,
      induces the oligomeric dissociation, without promoting the subunits unfolding and
      heme iron oxidation. Our results suggest that the MM of the annelid hemoglobin
      subunits is conserved to a great extent in the evolution process of these
      species. 

PMID- 24095793
TI  - Cloning and expression of selenoprotein W from pearl mussels Cristaria plicata.
AB  - Selenoprotein W (SelW) is a selenocysteine containing protein with redox activity
      involved in the antioxidant response. In this study, a selenoprotein W was cloned
      from pearl mussel Cristaria plicata (designated as CpSelW), and the expression
      patterns were characterized in tissues after Aeromonas hydrophila challenged. The
      full-length cDNA of cpSelW was of 858bp, containing a 5' untranslated region
      (UTR) of 145bp, a 3' UTR of 455bp with a poly (A) tail, and an open reading frame
      (ORF) of 258bp encoding a polypeptide of 85 amino acids with the predicted
      molecular mass of 9.277kDa, which shared 61% identity with SelW from Gallus
      gallus. A tertiary structure model generated for the CpSelW displayed a beta
      alpha-beta-beta-beta-alpha secondary structure pattern, which was similar to
      mouse SelW protein 3D structure. The mRNA of CpSelW was constitutively expressed
      in tested tissues of healthy mussel, including mantle, gill, hemocytes, muscle,
      and hepatopancreas, and it was highly expressed in hepatopancreas. After mussels
      were stimulated by A. hydrophila, the mRNA expression of CpSelW in hemocytes at
      6, 12 and 24h, in gill at 12h and in hepatopancreas at 24h was significantly down
      regulated. 

PMID- 24095794
TI  - Increased metalloprotease activity in the epileptogenic lesion--Lobectomy reduces
      metalloprotease activity and urokinase-type uPAR circulating levels.
AB  - Inflammation influences the pathogenesis of seizures by boosting neuronal
      degeneration of temporal lobe epilepsy with hippocampal sclerosis (TLE-HS). This
      work aimed to determine the activity of metalloproteases (MMPs) in brain tissue
      fragments of TLE-HS patients and the effect of lobectomy on circulating
      inflammatory biomarkers. Surgical fragments (n=4) from epileptogenic focus (EF) e
      perilesion area (PL), and control hippocampus from autopsy (n=5) were processed
      for glial protein (GFAP), activated microglia (IB4) immunohistochemistry, and
      metalloprotease activity (MMP-2, -9). Perilesional area showed GFAP positive
      cells with morphology of activate astrocyte and reactive gliosis nearby the
      lesion. In the lesion foci, astrocytes had altered cytoarchitecture with
      disorganized stroma suggestive of necrosis, and numerous mononuclear cells with
      few projections and morphological characteristics of activate microglia. Analysis
      of MMP-9 and MMP-2 in the sera before and after hippocampectomy confirmed the
      inflammatory pattern of TLE-HS, with high MMP-9 activity; high MMP-9/TIMP-1 and
      urokinase uPAR plasma levels before lobectomy but low after surgery. Maintenance
      of MMP-2 activity indicates persistent tissue remodeling in both groups. The
      present work shows that patients with chronic and medically intractable TLE-HS
      that undergone amigdalo-hippocampectomy for removal of epileptogenic lesion had a
      clinical enduring benefit of lack seizure recurrence for up to a year, and
      consistent reduction of proteases (MMP-9 and uPAR) activation that participate as
      important inflammatory epileptogenic inducers. 

PMID- 24095795
TI  - Effect of high-fat diet and antioxidants on hippocampal long-term potentiation in
      rats: an in vivo study.
AB  - The objective of this study was to determine the relation between the chronic
      consumption of a high-fat diet (HFD) and antioxidants on long-term potentiation
      (LTP) in dentate gyrus (DG) of the adult rat hippocampus in vivo. Forty adult
      male Wistar rats were randomly assigned into five groups (N=6-8): control group
      consumed an ordinary diet; HFD group received HFD only; ANO group received HFD
      plus antioxidants; RHFD group received a restricted HFD (30% less fat than the
      HFD group); and RANO group received restricted HFD plus antioxidants. Following 6
      months of controlled diets in each experimental group, the rats were anesthetized
      with intraperitoneal injection of ketamine and xylazin (100 and 2.5 mg/kg,
      respectively), and placed into a stereotaxic apparatus for surgery, electrode
      implantation and field potential recording. The population spike (PS) amplitude
      and slope of excitatory post synaptic potentials (EPSP) were measured in DG area
      of adult rats in response to stimulation applied to the perforant pathway (PP) by
      400 Hz tetanization. The results showed that HFD decreased EPSP slope and PS
      amplitude with respect to the control group, whereas antioxidants increased these
      parameters compared to the control group. It was suggested that chronic HFD
      consumption can impair hippocampal LTP in the granular cells of the DG, and
      antioxidant supplementation reverses the impairment of synaptic plasticity
      induced in DG.

PMID- 24095796
TI  - Regulation of embryonic neurotransmitter and tyrosine hydroxylase protein levels
      by ascorbic acid.
AB  - SCOPE: Ascorbic acid (ascorbate) is required to recycle tetrahydrobiopterin,
      which is necessary for neurotransmitter synthesis by the rate-limiting enzymes
      tyrosine and tryptophan hydroxylases. We sought to determine whether ascorbate
      might regulate embryonic brain cortex monoamine synthesis utilizing transgenic
      mouse models with varying intracellular ascorbate levels. METHODS AND RESULTS: In
      embryos lacking the sodium-dependent vitamin C transporter 2 (SVCT2), very low
      levels of brain ascorbate decreased cortex levels of norepinephrine and dopamine
      by approximately 33%, but had no effect on cortex serotonin or its metabolite, 5
      hydroxyindole acetic acid. This decrease in ascorbate also led to a decrease in
      protein levels of tyrosine hydroxylase, but not of tryptophan hydroxylase.
      Increased cortex ascorbate in embryos carrying extra copies of the SVCT2 resulted
      in increased levels of dopamine and its metabolite, 3,4-dihydroxyphenylacetic
      acid (DOPAC), as well as serotonin and 5-hydroxyindole acetic acid. CONCLUSION:
      The dependence of embryonic brain cortex neurotransmitter synthesis and tyrosine
      hydroxylase expression on intracellular ascorbate emphasizes the importance of
      receiving adequate ascorbate during development.

PMID- 24095797
TI  - Fructose-1,6-diphosphate protects against epileptogenesis by modifying cation
      chloride co-transporters in a model of amygdaloid-kindling temporal epilepticus.
AB  - Fructose-1,6-diphosphate (FDP) shifts the metabolism of glucose from glycolysis
      to the pentose phosphate pathway and has anticonvulsant activity in several acute
      seizure animal models. In the present study, we investigated the anti
      epileptogenic effects of FDP in an amygdaloid-kindling seizure model, which is an
      animal model of the most common form of human temporal lobe epilepsy. We found
      that 1.0 g/kg FDP slowed seizure progression and shortened the corresponding
      after-discharge duration (ADD). FDP increased the number of stimulations needed
      to reach seizure stages 2-5 and prolonged the cumulative ADD prior to reaching
      stages 3-5. It also shortened staying days and cumulative ADD in stages 4-5.
      However, it demonstrated no significant protective effect when administered after
      the animals were fully kindled. In hippocampal neurons, cation-chloride co
      transporters (CCCs) are suggested to play interesting roles in epilepsy by
      modulating gamma-aminobutyric acid (GABA)ergic activity through controlling GABAA
      receptor-mediated reversal potential. We examined the potential link between FDP
      and the hippocampal expression of two main members of the CCCs: the neuron
      specific K(+)-Cl(-)co-transporter 2 (KCC2) and Na(+)-K(+)-Cl(-)co-transporter 1
      (NKCC1). FDP inhibited the kindling-induced downregulation of KCC2 expression and
      decreased NKCC1 expression during the kindling session. Taken together, our data
      reveal that FDP may have protective activity against epileptogenesis, from
      partial to generalized tonic-clonic seizures. Furthermore, our findings suggest
      that the FDP-induced imbalance between KCC2 and NKCC1 expression may be involved
      in the neuroprotective effect.

PMID- 24095798
TI  - Water-use efficiency and relative growth rate mediate competitive interactions in
      Sonoran Desert winter annual plants.
AB  - PREMISE OF THE STUDY: A functional approach to investigating competitive
      interactions can provide a mechanistic understanding of processes driving
      population dynamics, community assembly, and the maintenance of biodiversity. In
      Sonoran Desert annual plants, a trade-off between relative growth rate (RGR) and
      water-use efficiency (WUE) contributes to species differences in population
      dynamics that promote long-term coexistence. Traits underlying this trade-off
      explain variation in demographic responses to precipitation as well as life
      history and phenological patterns. Here, we ask how these traits mediate
      competitive interactions. * METHODS: We conducted competition trials for three
      species occupying different positions along the RGR-WUE trade-off axis and
      compared the effects of competition at high and low soil moisture. We compared
      competitive effect (ability to suppress neighbors) and competitive response
      (ability to withstand competition from neighbors) among species. * KEY RESULTS:
      The RGR-WUE trade-off predicted shifts in competitive responses at different soil
      moistures. The high-RGR species was more resistant to competition in high water
      conditions, while the opposite was true for the high-WUE species. The
      intermediate RGR species tended to have the strongest impact on all neighbors, so
      competitive effects did not scale directly with differences in RGR and WUE among
      competitors. * CONCLUSIONS: Our results reveal mechanisms underlying long-term
      variation in fitness: high-RGR species perform better in years with large,
      frequent rain events and can better withstand competition under wetter
      conditions. The opposite is true for high-WUE species. Such resource-dependent
      responses strongly influence community dynamics and can promote coexistence in
      variable environments.

PMID- 24095799
TI  - Molecular cross talk between Notch1, Shh and Akt pathways during erythroid
      differentiation of K562 and HEL cell lines.
AB  - Erythropoiesis is a tightly regulated process dependent on extrinsic signals
      conveyed by the bone marrow niche. The signalling pathways thus activated or
      repressed do not act in isolation; rather an intricate cross talk among these
      pathways ensues homoeostasis within the erythroid compartment. In this study, we
      describe the effects of two such signalling pathways namely the Notch1 and the
      Shh pathway on erythropoiesis in immortalised K562 and HEL cell lines as well as
      the cross talk that ensues between them. We show that while activation of the
      Notch1 pathway inhibits differentiation of erythroid lineage cell lines as well
      as in in-vitro primary erythroid cultures from the human CD34(+) cells; Shh
      pathway favours erythroid differentiation. Further, the Notch1 pathway activates
      the Akt pathway and constitutively active Akt partially mimics the effect of
      Notch1 activation on erythropoiesis. Moreover, the Notch1, Akt and Shh pathways
      were found to cross talk with each other. In this process, activation of Notch1
      was found to down regulate the Shh pathway independent of Akt activation.
      Significantly, Notch1 not only down regulated the Shh pathway, but also inhibited
      recombinant Shh mediated erythropoiesis. Our study thus reveals an intricate
      crosstalk among the Notch1, Shh and Akt pathways wherein Notch1 emerges as a key
      regulator of erythropoiesis.

PMID- 24095800
TI  - Complete nucleotide sequence of the self-transmissible TOL plasmid pD2RT provides
      new insight into arrangement of toluene catabolic plasmids.
AB  - In the present study we report the complete nucleotide sequence of the toluene
      catabolic plasmid pD2RT of Pseudomonas migulae strain D2RT isolated from Baltic
      Sea water. The pD2RT is 129,894 base pairs in size with an average G+C content of
      53.75%. A total of 135 open reading frames (ORFs) were predicted to encode
      proteins, among them genes for catabolism of toluene, plasmid replication,
      maintenance and conjugative transfer. ORFs encoding proteins with putative
      functions in stress response, transposition and site-specific recombination were
      also predicted. Analysis of the organization and nucleotide sequence of pD2RT
      backbone region revealed high degree of similarity to the draft genome sequence
      data of the plant-pathogenic pseudomonad Pseudomonas syringae pv. glycinea strain
      B076, exhibiting relatedness to pPT23A plasmid family. The pD2RT backbone is also
      closely related to that of pGRT1 of Pseudomonas putida strain DOT-T1E and pBVIE04
      of Burkholderia vietnamiensis strain G4, both plasmids are associated with
      resistance to toluene. The ability of pD2RT to self-transfer by conjugation to P.
      putida recipient strain PaW340 was experimentally determined. Genetic
      organization of toluene-degrading (xyl) genes and flanking DNA segments resembles
      the structure of Tn1721-related class II transposon Tn4656 of TOL plasmid pWW53
      of P. putida strain MT53. The complete sequence of the plasmid pD2RT extends the
      known range of xyl genes carriers, being the first completely sequenced TOL
      plasmid, which is not related to well-studied IncP plasmid groups. We also
      verified the functionality of the catabolic route encoded by pD2RT by monitoring
      the expression of the xylE gene in pD2RT bearing hosts along with bacterial
      strains containing TOL plasmid of IncP-9 group. The growth kinetics of plasmid
      bearing strains was found to be affected by particular TOL plasmid. 

PMID- 24095801
TI  - Sensitive liquid chromatography/mass spectrometry methods for quantification of
      pomalidomide in mouse plasma and brain tissue.
AB  - Pomalidomide was recently approved by the United States Food and Drug
      Administration for the treatment of patients with relapsed or refractory multiple
      myeloma who have received at least two prior therapies. As pomalidomide is
      increasingly evaluated in other diseases and animal disease models, this paper
      presents development and validation of a sensitive liquid chromatography tandem
      mass spectrometry assay for quantification of pomalidomide in mouse plasma and
      brain tissue to fill a gap in published preclinical pharmacokinetic and
      analytical data with this agent. After acetonitrile protein precipitation,
      pomalidomide and internal standard, hesperitin, were separated with reverse phase
      chromatography on a C-18 column with a gradient mobile phase of water and
      acetonitrile with 0.1% fomic acid. Positive atmospheric pressure chemical
      ionization mass spectrometry with selected reaction monitoring mode was applied
      to achieve 0.3-3000nM (0.082-819.73ng/mL) linear range in mouse plasma and 0.6
      6000pmol/g in brain tissue. The within- and between-batch accuracy and precision
      were less than 15% for both plasma and brain tissue. The method was applied to
      measure pomalidomide concentrations in plasma and brain tissue in a pilot mouse
      pharmacokinetic study with an intravenous dose of 0.5mg/kg. This assay can be
      applied for thorough characterization of pomalidomide pharmacokinetics and tissue
      distribution in mice. 

PMID- 24095802
TI  - Simultaneously enantiospecific determination of (+)-trans-khellactone, (+/-)
      praeruptorin A, (+/-)-praeruptorin B, (+)-praeruptorin E, and their metabolites,
      (+/-)-cis-khellactone, in rat plasma using online solid phase extraction-chiral
      LC-MS/MS.
AB  - Many chiral drugs are used as the racemic mixtures in clinical practice. The
      occurrence of enantioselectively pharmacological activities calls for the
      development of enantiospecific analytical approaches during pharmacokinetic
      studies of enantiomers. Sample preparation plays a key role during quantitative
      analysis of biological samples. In current study, a rapid and reliable online
      solid phase extraction-chiral high performance liquid chromatography-tandem mass
      spectrometry (online SPE-chiral LC-MS/MS) method was developed for the
      simultaneously enantiospecific quantitation of (+)-trans-khellactone (dTK), (+/-)
      cis-khellactone (d/lCK), (+/-)-praeruptorin A (d/lPA), (+/-)-praeruptorin B
      (d/lPB) and (+)-praeruptorin E (dPE), the main active angular-type
      pyranocoumarins (APs) in Peucedani Radix (Chinese name: Qian-hu) or the major
      metabolites of those APs, in rat plasma. The validation assay results described
      here show good selectivity and enantiospecificity, extraction efficiency,
      accuracy and precision with quantification limits (LOQs) of 2.57, 1.28, 1.28,
      1.88, 4.16, 4.16 and 4.18ngmL(-1) for dTK, lCK, dCK, dPA, dPB, lPB and dPE,
      respectively, while lPA was not detected in rat plasma due to the
      carboxylesterase(s)-mediated hydrolysis. In addition, the validated system was
      satisfactorily applied to characterize the pharmacokinetic properties of those
      components in normal and chronic obstructive pulmonary disease (COPD) rats
      following oral administration of Qian-hu extract. dCK and lCK were observed as
      the main herb-related compounds in plasma. Enantioselectively pharmacokinetic
      profiles occurred for dCK vs lCK, dPA vs lPA, and dPB vs lPB in either normal or
      COPD rats. The proposed whole system is expected to be a preferable analytical
      tool for in vivo study of chiral drugs, in particular for the characterization of
      enantioselectively pharmacokinetic profiles. 

PMID- 24095803
TI  - Quantitative determination of phenolic compounds by UHPLC-UV-MS and use of
      partial least-square discriminant analysis to differentiate chemo-types of
      Chamomile/Chrysanthemum flower heads.
AB  - A new rapid UHPLC-UV-QTOF/MS method has been developed for the simultaneous
      analysis of nine phenolic compounds [(Z)-2-beta-d-glucopyranosyloxy-4
      methoxycinnamic acid (cis-GMCA), chlorogenic acid, (E)-2-beta-d-glucopyranosyloxy
      4-methoxycinnamic acid (trans-GMCA), quercetagetin-7-O-beta-d-glucopyranoside,
      luteolin-7-O-beta-d-glucoside, apigenin-7-O-beta-d-glucoside, chamaemeloside,
      apigenin 7-O-(6"-O-acetyl-beta-d-glucopyranoside), apigenin] and one
      polyacetylene (tonghaosu) from the flower heads of Chamomile/Chrysanthemum
      samples. The chromatographic separation was achieved using a reversed phase C18
      column with a mobile phase of water and acetonitrile, both containing 0.05%
      formic acid. The ten compounds were completely separated within 15min at a flow
      rate of 0.25mL/min with a 2MUL injection volume. The different chemo-types of
      Chamomiles/Chrysanthemum displayed variations in the presence of chemical
      constituents. German Chamomile samples confirmed the presence of cis-GMCA, trans
      GMCA, apigenin-7-O-beta-d-glucoside and tonghaosu as major constituents whereas
      Roman chamomile samples confirmed the presence of chamamaeloside and apigenin as
      major compounds. The Chrysanthemum morifolium samples showed the presence of
      luteolin-7-O-beta-d-glucose as the major compound. The method was applied for the
      analysis of various commercial products including capsules, tea bags, body and
      hair care products. LC-mass spectrometry with electrospray ionization (ESI)
      interface method is described for the evaluation of ten compounds in plant
      samples and commercial products. This method involved the detection of [M+Na](+)
      and [M+H](+) ions in the positive mode. Partial least squares discriminant
      analysis (PLS-DA) was used to visualize commercial samples quality and may be of
      value for discriminating between chamomile types and Chrysanthemum with regards
      to the relative content of individual constituents. The results indicated that
      the method is suitable as a quality control test for various
      Chamomile/Chrysanthemum samples and market products. 

PMID- 24095804
TI  - Validation of a method for the targeted analysis of 96 drugs in hair by UPLC
      MS/MS.
AB  - The method presented in this study allows the screening and quantification of 96
      drugs, from different groups: opiates, amphetamines, hallucinogens,
      benzodiazepines, antihistamines, antidepressants, antipsychotics, barbiturates
      and other sedatives, muscle relaxants, etc. in hair. Drugs are extracted from
      10mg of washed hair in 18h by a mixture of methanol:acetonitrile:ammonium formate
      (pH 5.3). Absolute recovery ranged from 70% to 106% for 75% of the analytes. The
      limits of detection in the low pg/mg range, may allow the detection of single
      dose drug exposure, with possible application in drug facilitated assaults (DFA);
      however, chronic use (compliance) can also be examined. The method has been fully
      validated for the drugs included in the study. The accuracy of the method was
      demonstrated by the analysis of certified authentic hair samples containing
      common drugs of abuse. The hair-method has broad potential as the measuring range
      is wide for the target analytes and new drugs can easily be added to the method
      due to the versatility of the extraction procedure and chromatographic system. 

PMID- 24095805
TI  - Leveraging nanochannels for universal, zero-order drug delivery in vivo.
AB  - Drug delivery is essential to achieve effective therapy. Herein we report on the
      only implantable nanochannel membrane with geometrically defined channels as
      small as 2.5 nm that achieves constant drug delivery in vivo. Nanochannels
      passively control the release of molecules by physico-electrostatic confinement,
      thereby leading to constant drug diffusion. We utilize a novel design algorithm
      to select the optimal nanochannel size for each therapeutic agent. Using
      nanochannels as small as 3.6 and 20 nm, we achieve sustained and constant plasma
      levels of leuprolide, interferon alpha-2b, letrozole, Y-27632, octreotide, and
      human growth hormone, all delivered at clinically-relevant doses. The device was
      demonstrated in dogs, rats, and mice and was capable of sustaining target doses
      for up to 70 days. To provide evidence of therapeutic efficacy, we successfully
      combined nanochannel delivery with a RhoA pathway inhibitor to prevent chronic
      rejection of cardiac allografts in a rat model. Our results provide evidence that
      the nanochannel platform has the potential to dramatically improve long-term
      therapies for chronic conditions.

PMID- 24095806
TI  - [Acute intestinal obstruction].
AB  - A 12-year-old boy is admitted for emergency surgery for acute abdominal syndrome.
      The intervention showed strangulation of the terminal ileum by the vermiform
      appendix. The pathology analysis showed bilharzial appendicitis by Schistosoma
      haematobium. The patient was treated with praziquantel. The literature is not
      plentiful on this subject. Because protozoiasis is endemic in this area, it
      should be looked for in all cases of appendicitis, as it requires medical
      treatment in addition to the appendectomy. 

PMID- 24095807
TI  - Emotional expression and heart rate in high-risk infants during the face-to
      face/still-face.
AB  - In infants, eye constriction-the Duchenne marker-and mouth opening appear to
      index the intensity of both positive and negative facial expressions. We combined
      eye constriction and mouth opening that co-occurred with smiles and cry-faces
      (respectively, the prototypic expressions of infant joy and distress) to measure
      emotional expression intensity. Expression intensity and heart rate were measured
      throughout the face-to-face/still-face (FFSF) in a sample of infants with
      prenatal cocaine exposure who were at risk for developmental difficulties. Smiles
      declined and cry-faces increased in the still-face episode, but the distribution
      of eye constriction and mouth opening in smiles and cry-faces did not differ
      across episodes of the FFSF. As time elapsed in the still face episode potential
      indices of intensity increased, cry-faces were more likely to be accompanied by
      eye constriction and mouth opening. During cry-faces there were also moderately
      stable individual differences in the quantity of eye constriction and mouth
      opening. Infant heart rate was higher during cry-faces and lower during smiles,
      but did not vary with intensity of expression or by episode. In sum, infants
      express more intense negative affect as the still-face progresses, but do not
      show clear differences in expressive intensity between episodes of the FFSF. 

PMID- 24095808
TI  - Cyclic mRNA expression of thyrotropin subunits and deiodinases in red drum,
      Sciaenops ocellatus.
AB  - The role of thyrotropin (thyroid-stimulating hormone, TSH) in driving peripheral
      thyroid function in non-mammalian species is still poorly understood. Thyroxine
      (T4), the principal hormone released from the thyroid gland in response to TSH
      stimulation, circulates with a robust daily rhythm in the teleost fish the red
      drum. Previous research suggests that the red drum T4 cycle is circadian in
      nature, driven by TSH secretion in the early photophase and inhibited by T4
      feedback in the early scotophase. To determine whether TSH is produced in a
      pattern consistent with feedback inhibition by this T4 cycle, we used
      quantitative real time PCR (qPCR) to quantify the daily cycle of expression of
      the pituitary TSH subunits GSUalpha, and TSHbeta. We found that TSH expression
      cycled inversely to, and 6-12 h out of phase with, the T4 cycle, consistent with
      the hypothesis that TSH secretion drives the T4 cycle. To examine the potential
      role of deiodinases in negative feedback regulation of this TSH cycle, we also
      utilized qPCR to assess the pituitary expression patterns of the TH activating
      enzyme outer-ring deiodinase (Dio2) and the TH deactivating enzyme inner-ring
      deiodinase (Dio3). Dio2 was not expressed with an obvious daily cycle, whereas
      Dio3 expression mirrored the expression of TSH. These results are consistent with
      circulating T4 providing the negative feedback signal controlling both TSH
      production and Dio3 expression in the pituitary, and suggest that TH inactivation
      by inner ring deiodination is an important component of TSH negative feedback
      control.

PMID- 24095809
TI  - Current perspectives on the androgen 5 alpha-dihydrotestosterone (DHT) and 5
      alpha-reductases in teleost fishes and amphibians.
AB  - The androgen 5 alpha-dihydrotestosterone (DHT) is a steroidogenic metabolite that
      has received little attention in non-mammalian species. DHT is produced by the
      reduction of the double-bond of testosterone by a group of enzymes called 5 alpha
      reductases of which there can be multiple isoforms (i.e., srd5a1, srd5a2, and
      srd5a3). Data from amphibians suggest that the expression of the srd5a genes
      occurs in early development, and continues until adulthood; however insufficient
      data exist in fish species, where DHT is thought to be relatively biologically
      inactive. Here, we demonstrate that fathead minnow (FHM; Pimephales promelas)
      developing embryos and adults express srd5a enzyme isoforms. During FHM
      embryogenesis, both srd5a1 and srd5a3 mRNA levels were significantly correlated
      in expression levels while srd5a2 showed a more unique pattern of expression. In
      adult FHMs, males had significantly higher levels of srd5a2 in the liver and
      gonad compared to females. In the male and female liver, transcript levels for
      srd5a2 were more abundant compared to srd5a1 and srd5a3, suggesting a prominent
      role for srd5a2 in this tissue. Interestingly, the ovary expressed higher mRNA
      levels of srd5a3 than the testis. Thus, data suggest that srd5a isoforms can show
      sexually dimorphic expression patterns in fish. We also conducted a literature
      review of the biological effects observed in embryonic and adult fish and
      amphibians after treatments with DHT and DHT-related compounds. Treatments with
      DHT in teleost fishes and amphibians have resulted in unexpected biological
      responses that are characteristic of both androgens and anti-androgens. For
      example, in fish DHT can induce vitellogenin in vitro from male and female
      hepatocytes and can increase 17beta-estradiol production from the teleost ovary.
      We propose, that to generate further understanding of the roles of DHT in non
      mammals, studies are needed that (1) address how DHT is synthesized within
      tissues of fish and amphibians; (2) examine the full range of biological
      responses to endogenous DHT, and its interactions with other signaling pathways;
      and (3) investigate how DHT production varies with reproductive stage. Lastly, we
      suggest that the Srd5a enzymes can be targets of endocrine disruptors in fish and
      frogs, which may result in disruptions in the estrogen:androgen balance in
      aquatic organisms. 

PMID- 24095810
TI  - Spontaneous intra-uterine growth restriction modulates the endocrine status and
      the developmental expression of genes in porcine fetal and neonatal adipose
      tissue.
AB  - Low birth weight is correlated with low adiposity at birth, a phenotype that
      influences neonatal survival and later adiposity. A better understanding of
      events affecting the fetal adipose tissue development and its functionality
      around birth is thus needed. This study was undertaken to examine the impact of
      spontaneous intra-uterine growth restriction (IUGR) on circulating concentrations
      of hormones and nutrients together with the developmental expression patterns of
      various genes in subcutaneous adipose tissue of pig fetus during the last third
      of pregnancy and just after birth. At 71 and 112 days post-conception and 2 days
      postnatal, pairs of same-sex piglets were chosen within litters to have either a
      medium (MBW) or a low (LBW) weight (n=6 pairs at each stage). The results
      indicate that IUGR counteracts the temporal fall of DLK1 gene expression in
      developing adipose tissue across gestation. It also attenuates the time-dependent
      increase in expression levels of many genes promoting adipocyte differentiation
      (PPARG, CEBPA) and lipogenesis (LPL, SREBF1, FASN, FABP4). Opposite responses to
      IUGR were observed for the IGF system, so that IGF1 mRNA levels were lower
      (P<0.001) but IGF2 mRNA levels were greater in adipose tissue of LBW piglets
      compared with MBW piglets. The plasma insulin concentration and the mRNA levels
      of insulin receptor (INSR) and insulin-responsive glucose transporter (GLUT4) in
      adipose tissue were also greater in LBW piglets at day 2 postnatal. The data
      indicate that IUGR delays the normal ontogeny of adipose tissue across gestation
      and affects the insulin and IGF axes around birth.

PMID- 24095811
TI  - Sensitivity of methanotrophic community structure, abundance, and gene expression
      to CH4 and O2 in simulated landfill biocover soil.
AB  - Pressure on mitigating CH4 emission in landfill requires better understanding of
      methanotrophs in landfill biocovers. Most previous studies focused on CH4 as the
      sole substrate. This study aims to understand the sensitivity of methanotrophs to
      both substrates CH4 and O2 concentrations in landfill biocovers. The estimated
      CH4 oxidation rates (4.66-98.7 * 10(-16) mol cell(-1) h(-1)) were evidently
      higher than the previous reports, suggesting that activity of methanotrophs was
      enhanced with both the increasing of O2 and CH4 concentrations. Denaturing
      gradient gel electrophoresis based on the amplification of pmoA genes suggested
      that methanotrophs were more sensitive to CH4 than O2. Quantification of
      methanotrophs using pmoA- and mmoX-targeted real-time polymerase chain reaction
      showed that Mbac and Mcoc as well as Mcys groups were significantly dominant.
      Mbac group with pmoA gene transcription was dominant. Results indicate that CH4
      mitigation would have higher potential by increasing O2 at appropriate CH4
      concentrations. 

PMID- 24095812
TI  - Physiological and molecular responses of springtails exposed to phenanthrene and
      drought.
AB  - Interaction between effects of hazardous chemicals in the environment and adverse
      climatic conditions is a problem that receives increased attention in the light
      of climate change. We studied interactive effects of phenanthrene and drought
      using a test system in which springtails (Folsomia candida Willem) were
      concurrently exposed to a sublethal phenanthrene level via passive dosing from
      silicone (chemical activity of 0.010), and sublethal drought from aqueous NaCl
      solutions (water activity of 0.988). Previous studies have shown that the
      combined effects of high levels of phenanthrene and drought, respectively,
      interact synergistically when using lethality as an end-point. Here, we
      hypothesized that phenanthrene interferes with physiological mechanisms involved
      in drought tolerance, and that drought influences detoxification of phenanthrene.
      However, this hypothesis was not supported by data since phenanthrene had no
      effect on drought-protective accumulation of myo-inositol, and normal water
      conserving mechanisms of F. candida were functioning despite the near-lethal
      concentrations of the toxicant. Further, detoxifying induction of cytochrome P450
      and glutathione-S-transferase was not impeded by drought. Both phenanthrene and
      drought induced transcription of heat shock protein (hsp70) and the combined
      effect of the two stressors on hsp70 transcription was additive, suggesting that
      the cellular stress and lethality imposed by these levels of phenanthrene and
      drought were also additive. 

PMID- 24095813
TI  - Assessing exposure risks for aquatic organisms posed by Tamiflu use under
      seasonal influenza and pandemic conditions.
AB  - Environmental pollution by anti-influenza drugs is increasingly recognized as a
      threat to aquatic environments. However, little is known about empirical data on
      risk effects posed by environmentally relevant concentrations of anti-influenza
      drug based on recently published ecotoxicological researches in Taiwan. Here we
      linked ecotoxicology models with an epidemiological scheme to assess exposure
      risks of aquatic organisms and environmental hazards posed by antiviral
      oseltamivir (Tamiflu) use in Taiwan. Built on published bioassays, we used
      probabilistic risk assessment model to estimate potential threats of
      environmentally relevant hazards on algae, daphnid, and zerbrafish. We found that
      Tamiflu use was unlikely to pose a significant chronic environmental risk to
      daphnia and zebrafish during seasonal influenza. However, the chronic
      environmental risk posed by Tamiflu use during pandemic was alarming. We conclude
      that no significant risk to algal growth was found during seasonal influenza and
      high pandemic Tamiflu use. 

PMID- 24095815
TI  - A novel bi-layer ascending release osmotic pump tablet: in vitro investigation
      and in vivo investigation in pharmacokinetic study and IVIVC evaluation.
AB  - This study was aimed to develop an ascending release push-pull osmotic pump
      (APOP) system with a novel mechanism and an easy manufacture process. Theoretical
      analysis showed that the key to obtain the non-zero order drug release was to
      break the balance between the drug suspension release rate in the drug layer and
      the swelling rate of the core, and an ascending drug release rate was achieved
      when the former was slower than the latter. A polymer (Polyox WSR N-12K) was
      introduced as a suspension agent in drug layer to slow down the hydration rate of
      drug layer. Influence of the composition of drug layer (PEO category, total
      amount, drug loading and fraction of NaCl), push layer (NaCl amount), and also
      the level of coating weight gain on the drug release profiles was investigated.
      Observation of hydration state was estimated by taking photos, and also was
      confirmed by the theories. Paliperidone was delivered successfully by APOP at an
      ascending release rate up to 20 h in vitro. The in vivo plasma concentration of
      paliperidone in beagle dogs increased gradually up to 19 h. The APOP with an easy
      manufacture process was a promising strategy to deliver drug at an ascending
      rate.

PMID- 24095814
TI  - Modeling healthy male white matter and myelin development: 3 through 60months of
      age.
AB  - An emerging hypothesis in developmental and behavioral disorders is that they
      arise from disorganized brain messaging or reduced connectivity. Given the
      importance of myelin to efficient brain communication, characterization of myelin
      development in infancy and childhood may provide salient information related to
      early connectivity deficits. In this work, we investigate regional and whole
      brain growth trajectories of the myelin water fraction, a quantitative magnetic
      resonance imaging measure sensitive and specific to myelin content, in data
      acquired from 122 healthy male children from 3 to 60months of age. We examine
      common growth functions to find the most representative model of myelin
      maturation and subsequently use the best of these models to develop a continuous
      population-averaged, four-dimensional model of normative myelination. Through
      comparisons with an independent sample of 63 male children across the same age
      span, we show that the developed model is representative of this population. This
      work contributes to understanding the trajectory of myelination in healthy
      infants and toddlers, furthering our knowledge of early brain development, and
      provides a model that may be useful for identifying developmental abnormalities. 

PMID- 24095816
TI  - Rheological investigation of the shear strength, durability, and recovery of
      alginate rafts formed by antacid medication in varying pH environments.
AB  - The mechanical response of alginate rafts formed by mixing liquid alginate
      antacid medication (Gaviscon Extra Strength Liquid Antacid) with acidic solutions
      was investigated by deforming isolated rafts in a shear rheometer. As rafts were
      deformed to varying magnitudes of applied strain, rheological parameters were
      identified and related to the overall strength, durability, and recoverability of
      rafts formed at different pH (1.1-1.7) and aging conditions (0.5-4 h). Rafts
      formed in the lowest acidity solutions (pH 1.4, 1.7) were elastically weak ( G'0
      = 60 , 42 Pa for un-aged raft) yet maintained their elasticity during applied
      shear deformation to large values of strain (gammac~90%, 50%, where G'~G"), and
      displayed a low-to-moderate level of elastic recovery following large-strain
      deformation. Rafts formed in the highest acidity solution had the greatest
      strength ( G'0 = 500 Pa for un-aged raft and 21.5 kPa for rafts after 0.5 h of
      aging), reduced durability (gammac~2.5%, independent of aging), and displayed the
      greatest recoverability. A trade-off existed between un-aged raft strength and
      durability while recovery was dependent on durability, solution pH, and age.
      Rheometry-based evaluations of alginate rafts could be used for the informed
      design of future gastric retention and antacid products.

PMID- 24095817
TI  - Publication of the special issue "Fourth European workshop on lipid mediators".

PMID- 24095818
TI  - Craniosynostosis, anal anomalies, and porokeratosis (CDAGS syndrome): case report
      and literature review.
AB  - CDAGS syndrome is an autosomal recessive syndrome characterized by
      craniosynostosis, large open fontanelles, hearing loss, anal anomalies,
      genitourinary malformations and porokeratosis. To our knowledge, only four
      families from different geographic regions and ethnic backgrounds have been
      reported until now and no molecular defect has been identified. Here we report
      two sisters presenting with craniosynostosis, microcephaly, short downslanting
      palpebral fissures, sparse hair, eyelashes, and eyebrows and porokeratosis that
      appeared at the age of one month. The youngest sister had an imperforate anus
      with rectoperineal fistula. Array-CGH did not reveal any pathological CNV.
      Molecular analysis of the c16orf57, RECQL4 and MCM5 genes was normal.

PMID- 24095819
TI  - A novel mutation in STXBP1 causing epileptic encephalopathy (late onset infantile
      spasms) with partial respiratory chain complex IV deficiency.
AB  - STXBP1 (MUNC18.1), encoding syntaxin binding protein 1, has been reported in
      Ohtahara syndrome, a rare epileptic encephalopathy with suppression burst pattern
      on EEG, in patients with infantile spasms and in a few patients with nonsyndromic
      mental retardation without epilepsy. We report a patient who presented late onset
      infantile spasms. Epilepsy was controlled but the patient developed severe mental
      delay. A first diagnosis of mitochondrial disease was based on clinical
      presentation and on a partial deficit of respiratory chain complex IV, but
      molecular screening for mitochondrial genes was negative. The sequencing of
      STXBP1 gene found a de novo nonsense mutation (c.585C>G/p.Tyr195X). This
      observation widens the clinical spectrum linked to STXBP1 mutations with the
      description of a patient with late onset infantile spasms. It raises the question
      of the value of epilepsy genes screening in patients with uncertain, partial or
      unconfirmed mitochondrial dysfunction.

PMID- 24095820
TI  - Novel MNX1 mutations and clinical analysis of familial and sporadic Currarino
      cases.
AB  - Currarino Syndrome (CS) is a rare congenital malformation characterized by three
      major clinical aspects: sacral anomalies, anorectal malformation and presacral
      mass. In familial settings the disorder is transmitted as autosomal dominant
      trait, with a wide phenotype variability and low penetrance. The causative gene
      of CS is the motor neuron and pancreas homeobox-1 (MNX1), mapped at 7q36, and
      coding for a transcription factor. Mutations in the MNX1 have been implicated in
      almost all familial but only in 30% of sporadic cases. In our cohort of 28 CS
      cases, 8 were familiar, 18 were sporadic and 2 were not determined cases. We
      performed mutational analysis of MNX1 in all cases by DNA sequencing as well as
      by Multiplex Ligation-dependent Probe Amplification (MLPA) in those CS cases
      where no MNX1 mutations were found, to exclude a MNX1 heterozygous loss. We
      identified 10 novel and 4 recurrent mutations. Among the novel mutations, 2 were
      frameshift variants (p.Ser4IlefsX52, p.Phe248SerfsX35), 6 were missense variants
      (p.Pro27Leu, p.Gly103Arg, p.Leu254Pro, p.Leu278Pro, p.Glu282Lys, p.Arg292Gly),
      one was a non-sense variant (p.Lys297X), and the last one was a synonymous
      variant (p.Gln290Gln). Mutated patients showed a variability of phenotypes but
      all share at least the association of sacral agenesis and presacral mass, and
      this co-occurrence can constitute a pathognomonic sign to perform MNX1 analysis.
      Genetic heterogeneity could be a possible explanation for some of the sporadic
      not mutated patients even if a mis-diagnosis could not be excluded. Finally, we
      provide an up-date of the more recent literature, reporting a total number of 82
      MNX1-CS related mutations.

PMID- 24095821
TI  - [Utility of the PET/CT in vulvar cancer management].
AB  - OBJECTIVE: To describe the clinical impact of PET/CT in the management of
      patients with vulvar cancer. MATERIAL AND METHODS: Retrospective analysis of 13
      PET/CT studies with (18)F-FDG (6 staging and 7 suspected recurrence)
      corresponding to 10 patients diagnosed with vulvar cancer by biopsy, with a mean
      age of 64.5 years. The preoperative PET/CT study was analyzed qualitatively
      according to the lesion region. Surgical excision was carried out, covering all
      the suspected areas according to the PET/CT study. This was compared with the
      histopathologic analysis. RESULTS: Abnormal vulvar PET/CT uptake was found in 9
      out of the 13 studies and invasion of adjacent structures in 5 of them (urethra,
      perineal, vagina). The inguinal-femoral lymph nodes were considered as affected
      in 3 studies and one pelvic lymph node was also affected. Four of the studies had
      extralymphatic involvement: 3 in lung and 1 in ischiorectal fossa. The PET/CT
      showed a 100% sensitivity for the detection of the vulvar lesion in squamous cell
      carcinomas and 60% in non-squamous cell ones. There was a false positive result
      for local invasion due to urine contamination. One of the studies with lung
      metastases was related to a synchronous breast tumor. All the pathological lymph
      node levels detected in the PET/CT study were confirmed in the histopathology
      study. No new lesions were identified by surgery. PET/CT changed the therapeutic
      management in 8/13 studies (61.5%). CONCLUSIONS: PET/CT is postulated as a useful
      imaging test for the management of vulvar cancer, mainly in the identification of
      nodal metastases. It may affect both surgical planning and clinical management.
      Larger series are needed to confirm our findings.

PMID- 24095822
TI  - Mangiferin attenuates MPTP induced dopaminergic neurodegeneration and improves
      motor impairment, redox balance and Bcl-2/Bax expression in experimental
      Parkinson's disease mice.
AB  - Mangiferin, a polyphenol compound of C-glucoside, is well-known for its anti
      inflammatory, antioxidant, anticancer, antidiabetic and cognitive enhancement
      properties. In this study, we investigated the neuroprotective effect of
      mangiferin against 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) mouse
      model of Parkinson's disease (PD), which is most popular and widely used to
      evaluate therapeutic implications of new protective agents. Male C57BL/6 mice
      were orally treated with mangiferin (10, 20 and 40 mg/kg body wt.) for 14 days
      and from 10th day onwards MPTP (30 mg/kg, i.p.) was injected for last 5 days.
      MPTP treatment leads to enhanced oxidative stress, induction of apoptosis
      (upregulates the expression of Bax, proapoptotic protein and downregulates the
      expression of anti-apoptotic marker Bcl-2), and loss of dopominergic neurons
      which results in motor impairments. Results of our study confirmed that
      mangiferin prevented MPTP-induced behavioral deficits, oxidative stress,
      apoptosis, dopaminergic neuronal degeneration and dopamine depletion. Taken
      together, we conclude that mangiferin attenuates the dopaminergic
      neurodegeneration mainly through its potent antioxidant and antiapoptotic
      properties.

PMID- 24095823
TI  - Diabetes-induced morphological, biomechanical, and compositional changes in
      ocular basement membranes.
AB  - The current study investigates the structural and compositional changes of ocular
      basement membranes (BMs) during long-term diabetes. By comparing retinal vascular
      BMs and the inner limiting membrane (ILM) from diabetic and non-diabetic human
      eyes by light and transmission electron microscopy (TEM), a massive, diabetes
      related increase in the thickness of these BMs was detected. The increase in ILM
      thickness was confirmed by atomic force microscopy (AFM) on native ILM flat-mount
      preparations. AFM also detected a diabetes-induced increase in ILM stiffness. The
      changes in BM morphology and biophysical properties were accompanied by partial
      changes in the biochemical composition as shown by immunocytochemistry and
      western blots: agrin, fibronectin and tenascin underwent relative increases in
      concentration in diabetic BMs as compared to non-diabetic BMs. Fibronectin and
      tenascin were particularly high in the BMs of outlining microvascular aneurisms.
      The present data showed that retinal vascular BMs and the ILM undergo
      morphological, biomechanical and compositional changes during long-term diabetes.
      The increase in BM thickness not only resulted from an up-regulation of the
      standard BM proteins, but also from the expression of diabetes-specific
      extracellular matrix proteins that are not normally found in retinal BMs. 

PMID- 24095824
TI  - [The Albert Schweitzer legacy].

PMID- 24095825
TI  - Trends in the prevalence of recorded isolated hypospadias in Hungarian newborn
      infants during the last 50 years - a population-based study.
AB  - Previously an increasing birth prevalence of hypospadias was recorded in some
      countries, including in Hungary. However, a Hungarian clinical-epidemiological
      study estimated the so-called true birth prevalence of hypospadias (2.25+0.30 per
      1000) based on the physical examination of newborns with well-defined diagnostic
      criteria. Thus the aim of this study was the critical analysis of the recorded
      annual birth prevalences of cases with isolated hypospadias (IHS) in the
      Hungarian Congenital Abnormality Registry during the last 50 years compared to
      the true birth prevalence of IHS. There was increasing trend of annual recorded
      prevalence of IHS with a further increase between 2005 and 2011 with the maximum
      of 3.42 per 1000 in 2011. However, this increase can be explained by the more
      complete reporting of IHS and a larger proportion of mild coronal subgroup. In
      conclusion, birth defect-registries are not appropriate for the estimation of
      true birth prevalence of IHS. 

PMID- 24095826
TI  - Desmosterol and DHCR24: unexpected new directions for a terminal step in
      cholesterol synthesis.
AB  - 3beta-Hydroxysterol Delta(24)-reductase (DHCR24) catalyzes the conversion of
      desmosterol to cholesterol. This ultimate step of cholesterol biosynthesis
      appears to be remarkable in its diverse functions and the number of diseases it
      is implicated in from vascular disease to Hepatitis C virus (HCV) infection to
      cancer to Alzheimer's disease. This review summarizes the present knowledge on
      the DHCR24 gene, sterol Delta(24)-reductase protein and the regulation of both.
      In addition, the functions of desmosterol, DHCR24 and their roles in human
      diseases are discussed. It is apparent that DHCR24 exerts more complex effects
      than what would be expected based on the enzymatic activity of sterol Delta(24)
      reduction alone, such as its influence in modulating oxidative stress. Increasing
      information about DHCR24 membrane association, processing, enzymatic regulation
      and interaction partners will provide further fundamental insights into DHCR24
      and its many and varied biological roles.

PMID- 24095827
TI  - Regulation effects of TZQ-F on adipocyte differentiation and insulin action.
AB  - ETHNOPHARMACOLOGICAL RELEVANCE: TZQ has been used in traditional Chineses
      medicine for treating diabetes. Based on the recipe of traditional anti-diabetic
      formula TZQ, we have developed TZQ-F which has been in phase 2 clinical trails.
      To study the mechanisms by which TZQ-F ameliorates diabetes, we examined whether
      treatment with TZQ-F improves hyperinsulinemia, hyperglycemia and obesity in type
      2 diabetic KKA(y) mice and whether this is associated with an improvement of
      adipocyte differentiation and insulin action. METHODS: TZQ-F, fenofibrate,
      rosiglitazone or distilled water was administered to 7-week-old diabetic KKA(y)
      and nondiabetic C57BL/6J mice for 8 weeks. Insulin resistance index, body weight
      and levels of serum blood glucose, leptin, insulin and adiponectin were
      evaluated. The expression of peroxisome proliferator-activated receptor gamma
      (PPARgamma) in skeletal muscle and liver tissues were determined with real-time
      PCR and western boltting. The mRNA expressions of insulin receptor (InsR),
      insulin receptor substrate-1 (IRS-1), insulin receptor substrate-2 (IRS-2),
      glucose transporter-1 (Glut-1) and Phosphoenolpyruvate 3-kinases (PI3K) in
      skeletal muscle and liver tissues were determined with real-time PCR.
      Histopathology of liver has been observed. RESULTS: Treatment of TZQ-F for 8
      weeks ameliorated hyperglycemia, hyperinsulinemia, hyperleptinemia and
      hypoadiponectinemia in KKA(y) mice. TZQ-F also up-regulated expression of
      PPARgamma in liver tissue. However, it had no effect on regulation of expression
      of PPARgamma in muscle tissue. In addition, TZQ-F upregulates InsR, IRS-1, IRS-2,
      Glut-1, and PI3K mRNA expression. Consistent with the in vivo results, histology
      study demonstrated that TZQ-F alleviated pathologic changes of the liver induced
      by high-fat diet. CONCLUSIONS: These results first indicate that TZQ-F can be
      beneficial for reducing hyperinsulinemia, hyperglycemia and obesity through its
      potency of regulating adipocyte differentiation and insulin action.

PMID- 24095828
TI  - Patterns of medicinal plant use by inhabitants of Brazilian urban and rural
      areas: a macroscale investigation based on available literature.
AB  - ETHNOPHARMACOLOGICAL RELEVANCE: Although the relationship between local people
      and plants may be idiosyncratic, some human behaviors are common to different
      communities and can be influenced by cultural and environmental factors. Thus,
      this study drew upon a systematic review and meta-analysis to evaluate if there
      are patterns of medicinal plant use in different Brazilian ethnobotanical studies
      and if these patterns are influenced by the urbanization or ecosystems where the
      studies were conducted. MATERIALS AND METHODS: The factors evaluated concerned
      the origin of the species used (native vs. exotic), plant habit (woody vs. non
      woody) and plant parts (permanent and non-permanent). Two kinds of analysis were
      performed: the integrative and the meta-analytical. RESULTS: The factors varied
      depending on the ecosystems in which the studies were conducted. In the Amazon,
      Cerrado and Caatinga, native and woody medicinal species dominated; conversely,
      this pattern was not the case for the Atlantic Forest and Pampas ecosystems.
      Permanent plant parts were predominant in the Cerrado, and considering only
      native plants, permanent parts dominated in the Amazon, Cerrado and Caatinga.
      Urbanization did not significantly affect these patterns. Additionally, the
      species relative importance (RI) did not change as a function of the ecosystem or
      the degree of urbanization. CONCLUSIONS: The phenomena observed in this study can
      be explained in light of the chemical ecology and historical and cultural aspects
      of the species, and the findings have important implications for bioprospecting
      and conservation.

PMID- 24095829
TI  - Korean red ginseng extract induces proliferation to differentiation transition of
      human acute promyelocytic leukemia cells via MYC-SKP2-CDKN1B axis.
AB  - ETHNOPHARMACOLOGICAL RELEVANCE: Korean red ginseng has been used as traditional
      medicine in East Asia. Recent scientific research revealed multiple effects of
      Korean red ginseng, including anticancer activity. To evaluate the effect of
      Korean red ginseng extract (KRGE) in acute promyelocytic leukemia (APL) and
      elucidate its molecular mechanism. MATERIALS AND METHODS: NB4 cells were treated
      with 1mg/ml KRGE for 48 h and examined for cell proliferation and
      differentiation. Cell cycle distribution of KRGE-treated cells was analyzed and
      the expression level of G1 phase regulators was determined. MYC was overexpressed
      by retroviral transduction and its effect on SKP2 and CDKN1B gene expression,
      cell proliferation, cell cycle and differentiation was evaluated in KRGE-treated
      cells. RESULTS: KRGE alone was sufficient to induce granulocytic differentiation
      accompanied with growth inhibition. KRGE treatment resulted in cell cycle arrest
      at the G1 phase with augmented Cdkn1b proteins without changes in transcript
      levels. Cycloheximide treatment revealed reduced degradation of Cdkn1b protein by
      KRGE. In addition, KRGE treatment reduced expression of MYC and SKP2 genes, both
      at mRNA and protein levels. Upon ectopic expression of MYC, the effect of KRGE
      was reversed with lesser reduction and induction of SKP2 gene and Cdkn1b protein,
      respectively. Taken together, these results suggest a sequential molecular
      mechanism from MYC reduction, SKP2 reduction, Cdkn1b protein stabilization, G1
      phase arrest to granulocytic differentiation by KRGE in human APL. CONCLUSIONS:
      KRGE induces leukemic proliferation to differentiation transition in APL through
      modulation of the MYC-SKP2-CDKN1B axis.

PMID- 24095830
TI  - Isolation of seselin from Clausena anisata (Rutaceae) leaves and its effects on
      the feeding and development of Lucilia cuprina larvae may explain its use in
      ethnoveterinary medicine.
AB  - ETHNOPHARMACOLOGICAL RELEVANCE: The leaves of Clausena anisata are used
      traditionally to expel maggots from wounds of animals in Zimbabwe. We have
      previously proved in the laboratory that the plant certainly affects the
      behaviour and growth of blowfly larvae. The objective of this study was to
      isolate and identify the active compounds responsible for this activity.
      MATERIALS AND METHODS: The acetone extract of Clausena anisata leaf powder was
      separated by solvent-solvent partition into five fractions. The n-hexane fraction
      was the most active in the larvicidal assay and therefore subjected to open
      column chromatography on silica gel. RESULTS: The isolated compound was
      identified by nuclear magnetic resonance (NMR) and mass spectroscopy (MS) as the
      pyranocoumarin, seselin, chemically known as 2',2'-dimethylpyranocoumarin. It
      inhibited feed intake in the first and second instars of blowfly larvae at the
      minimum concentration tested of 1 ppm resulting in significant lower mass pupae
      (13.5+/-0.5 mg and 22.4+/-0.4 mg for the first and second instar larvae
      respectively) compared to the solvent control group (26.19+/-0.8 mg) (p<0.05).
      CONCLUSIONS: This is the first report of the isolation of seselin from the leaves
      of Clausena anisata and the first report of the compound having an effect against
      blowfly larvae.

PMID- 24095831
TI  - Anti-hyperglycemic and hypolipidemic effects of Cistanche tubulosa in type 2
      diabetic db/db mice.
AB  - ETHNOPHARMACOLOGICAL RELEVANCE: The dried succulent stem of Cistanche tubulosa
      (Schenk) R. Wight is one component of traditional Chinese medicine prescriptions
      for diabetes. However, there have been no modern scientific reports to confirm
      this traditional claim for the Cistanche species until now. Thus, we investigated
      the effects of Cistanche tubulosa on glucose homeostasis and serum lipids in male
      BKS.Cg-Dock7(m) +/+ Lepr(db)/J (db/db) mice, a model of type 2 diabetes.
      MATERIALS AND METHODS: The verbascoside and echinacoside contents of Cistanche
      tubulosa powder were evaluated using HPLC. The total phenolic content,
      polysaccharide content and antioxidant activity of Cistanche tubulosa powder were
      also evaluated. Then, different doses of Cistanche tubulosa (equivalent to 120.9,
      72.6 or 24.2mg verbascoside/kg) were administered orally once daily for 45 days
      to male db/db mice. Age matched db/+ mice were used as normal controls. Body
      weight, fasting blood glucose, postprandial blood glucose and insulin tolerance
      test were measured during the experiment. At the time of sacrifice, blood was
      collected for measurement of insulin level, the homeostatic model assessment of
      insulin resistance (HOMA-IR), and total cholesterol, triglyceride, HDL-c, LDL-c
      and VLDL-c levels; liver and muscle were harvested for measurement of glycogen
      levels. RESULTS: Cistanche tubulosa significantly suppressed the elevated fasting
      blood glucose and postprandial blood glucose levels, improved insulin resistance
      and dyslipidemia, and suppressed body weight loss in db/db mice. However,
      Cistanche tubulosa did not significantly affect serum insulin levels or hepatic
      and muscle glycogen levels. CONCLUSION: This study provides scientific evidence
      for the traditional use of Cistanche tubulosa to treat diabetes, suggesting that
      Cistanche tubulosa has the potential for development into a functional food
      ingredient or drug to prevent hyperglycemia and treat hyperlipidemia.

PMID- 24095832
TI  - In vivo antiprostate tumor potential of Vernonia guineensis Benth. (Asteraceae)
      tuber extract (VGDE) and the cytotoxicity of its major compound pentaisovaleryl
      sucrose.
AB  - ETHNOPHARMACOLOGICAL RELEVANCE: Vernonia guineensis Benth. (Asteraceae) root
      decoction is used in folk medicine in Cameroon to treat some ailments including
      prostate cancer. The aim of this study was to validate the claimed antiprostate
      cancer activity of Vernonia guineensis Benth. in vivo and to investigate the
      cytotoxicity of a pentaisovaleryl sucrose isolated from Vernonia guineensis on
      some cancer cell lines. MATERIALS AND METHODS: A crude dichloromethane extract of
      Vernonia guineensis (VGDE) was used for this study. For in vivo antiprostate
      cancer efficacy, nude mice (n=16) were injected subcutaneously with prostate
      cancer PC-3 cells. Upon the formation of the xenograft tumors, the mice were
      divided into two equal groups with approximately the same mean tumor volume per
      group. One group was treated with VGDE orally (500 mg/kg) and the other with a
      vehicle control for 30 days. Body weight and tumor volumes were measured 2* a
      week and on the 33rd day, the mice were euthanized and tumors harvested and
      weighed. For the cytotoxicity study, the WST-1 assay was used to determine the
      activity of pentaisovaleryl sucrose previously isolated from VGDE. The cancer
      cell lines used in the cytotoxicity study included breast, colon, leukemia, lung,
      melanoma, ovarian and prostate. RESULTS: Prostate cancer (PC-3) xenograft tumors
      treated with VGDE showed a significant decrease in tumor size (P=0.0295) compared
      to control. Pentaisovaleryl sucrose also demonstrated cytotoxicity against
      various cancer cell lines with IC50 values as follows: MDA-MD-231-6.66uM; MCF-7
      7.50 uM; HCT116-14.12 uM; A549-5.76 uM; HL60-6.43 uM; A375-8.64 uM; OVCAR3-9.53
      uM; Capan1-7.13 uM; Mia-Paca 6.47 uM. CONCLUSION: VGDE does possess in vivo
      activity against prostate tumor and has potential for development into a natural
      product for the treatment of prostate cancer. This study thus provides
      preliminary validation for the folk use of Vernonia guineensis against prostate
      conditions. Further in vivo studies are however required to confirm these results
      and to understand the mechanism of action of VGDE and the in vivo efficacy of
      pentaisovaleryl sucrose.

PMID- 24095833
TI  - The herbal formula CGX ameliorates the expression of vascular endothelial growth
      factor in alcoholic liver fibrosis.
AB  - ETHNOPHARMACOLOGIC RELEVANCE: The Chunggan extract (CGX) is a traditional herbal
      formula prescribed for patients suffering from various liver diseases, including
      alcoholic liver disease, in which the mechanism of CGX action remains unclear.
      This study aimed to investigate the anti-hepatic fibrosis effects of CGX and its
      underlying mechanisms in alcohol-induced rat livers. MATERIALS AND METHODS: To
      elucidate the mechanism of action of CGX, we evaluated gene expression profiles
      in the livers of rats treated with 30% alcohol and anti-fibrotic doses of CGX of
      100 and 200 mg/kg/day at 1 day, and 2 and 4 weeks using microarrays. The mRNA and
      protein expression levels of vascular endothelial growth factor (VEGF), one of
      the candidate genes selected in this study, in alcohol-induced rat livers were
      measured by real-time PCR and enzyme-linked immunosorbent assays, respectively.
      RESULTS: We identified 4128 genes as differentially expressed by at least twofold
      between alcohol-only- and alcohol-CGX-fed rats at various doses and time points,
      compared to naive control animals. Twenty-three of these genes were associated
      with liver fibrosis and oxidative stress based on the GeneCards database,
      resulting in p<0.05 by ANOVA between the alcohol-only and alcohol-CGX groups.
      Especially, Vegf was decreased in CGX 200 mg/kg/day-fed rat livers at all time
      points evaluated, and mRNA and protein levels at the 4-week time point were
      validated. CONCLUSION: These gene expression profiles provide a better
      understanding of the mechanisms underlying the anti-fibrotic effects of CGX.
      Suppression of VEGF may play a critical role in anti-fibrotic action of CGX in
      alcoholic liver injury.

PMID- 24095834
TI  - Role of long-chain acyl-coenzyme A synthetases in the regulation of arachidonic
      acid metabolism in interleukin 1beta-stimulated rat fibroblasts.
AB  - Acyl coenzyme A synthetase long-chain family members (ACSLs) are a family of
      enzymes that convert long-chain free fatty acids into their acyl-CoAs and play an
      important role in fatty acid metabolism. Here we show the role of ACSL isozymes
      in interleukin (IL)-1beta-induced arachidonic acid (AA) metabolism in rat
      fibroblastic 3Y1 cells. Treatment of 3Y1 cells with triacsin C, an ACSL
      inhibitor, markedly enhanced the IL-1beta-induced prostaglandin (PG)
      biosynthesis. Small interfering RNA-mediated knockdown of endogenous Acsl4
      expression increased significantly the release of AA metabolites, including PGE2,
      PGD2, and PGF2alpha, compared with replicated control cells, whereas knockdown of
      Acsl1 expression reduced the IL-1beta-induced release of AA metabolites.
      Experiments with double knockdown of Acsl4 and intracellular phospholipase A2
      (PLA2) isozymes revealed that cytosolic PLA2alpha, but not calcium-independent
      PLA2s, is involved in the Acsl4 knockdown-enhanced PG biosynthesis. Electrospray
      ionization mass spectrometry of cellular phospholipids bearing AA showed that the
      levels of some, if not all, phosphatidylcholine (PC) and phosphatidylinositol
      species in Acsl4 knockdown cells were decreased after IL-1beta stimulation, while
      those in control cells were not so obviously decreased. In Acsl1 knockdown cells,
      the levels of some AA-bearing PC species were reduced even in the unstimulated
      condition. Collectively, these results suggest that Acsl isozymes play distinct
      roles in the control of AA remodeling in rat fibroblasts: Acsl4 acts as the first
      step of enzyme for AA remodeling following IL-1beta stimulation, and Acsl1 is
      involved in the maintenance of some AA-containing PC species. 

PMID- 24095835
TI  - Establishing benchmarks and metrics for utilization management.
AB  - The changing environment of healthcare reimbursement is rapidly leading to a
      renewed appreciation of the importance of utilization management in the clinical
      laboratory. The process of benchmarking of laboratory operations is well
      established for comparing organizational performance to other hospitals (peers)
      and for trending data over time through internal benchmarks. However, there are
      relatively few resources available to assist organizations in benchmarking for
      laboratory utilization management. This article will review the topic of
      laboratory benchmarking with a focus on the available literature and services to
      assist in managing physician requests for laboratory testing. 

PMID- 24095836
TI  - Cross-cultural adaptation, reliability, internal consistency and validation of
      the Arabic version of the knee injury and osteoarthritis outcome score (KOOS) for
      Egyptian people with knee injuries.
AB  - OBJECTIVE: The objective of this study was to cross-culturally adapt and validate
      the Arabic version of the Knee injury and Osteoarthritis Outcome Score (KOOS)
      among a sample from Egyptian populace. METHODS: This version was obtained with
      forward/backward translations and pre-testing. The Arabic KOOS, the RAND-36-Item
      Health Survey (RAND-36) questionnaire, visual analogue scales (VAS) of pain and a
      form for patient characteristics were used. Test-retest reliability and internal
      consistency were assessed, using Intraclass Correlation Coefficient (ICC) and
      Cronbach's alpha, respectively. The dimensionality was assessed, by factor
      analysis and construct validity by using a priori hypothesized correlations with
      the RAND-36. Ceiling/floor effects and measurement error were tested as well.
      RESULTS: No major difficulties were encountered during the translation and pre
      testing stages. Reliability was acceptable with Cronbach's alpha coefficients
      between 0.80 and 0.95, and ICCs ranging from 0.88 to 0.96 for the KOOS subscales.
      Factor analysis was performed on the whole study population and the results
      indicated that all items of the Arabic KOOS loaded on one factor, which ranged
      from 0.34 to 0.89. Construct validity was supported by the confirmation of all
      priori hypotheses by the presence of higher correlations between similar
      constructs than between dissimilar constructs of the KOOS subscales, RAND-36
      subscales and VAS. Floor/ceiling effects were considered not to be present.
      CONCLUSION: The Arabic KOOS is a reliable and valid instrument that can be self
      administered to Egyptian patients and provides a valuable basis for research and
      clinical projects focussing on patient-based assessments in anterior cruciate
      ligament (ACL), meniscus and combined injures of knee. Further studies to
      validate the Arabic version of the KOOS using females and elderly population with
      different knee problems and various educational levels in other Arabic counties
      are highly recommended.

PMID- 24095837
TI  - Total knee replacement; minimal clinically important differences and responders.
AB  - OBJECTIVE: To provide new data on minimally clinical important difference (MCID)
      and percentages of responders on pain and functional dimensions of Western
      Ontario and McMaster Osteoarthritis Index (WOMAC) in patients who have undergone
      total knee replacement (TKR). METHODS: 1-year prospective multicentre study with
      two different cohorts. Consecutive patients on the waiting list were recruited.
      There were 415 and 497 patients included. Pain and function were collected by the
      reverse scoring option of the WOMAC (0-100, worst to best). Transition items
      (five point scale) were collected at 1-year and MCID was calculated through mean
      change in patients somewhat better, Receiver Operating Characteristic (ROC) and
      two other questions about satisfaction. Analysis was performed in the whole
      sample and by tertiles of baseline severity. Likewise were calculated the
      percentages of patients who attained cut-off values. RESULTS: Global MCID for
      pain were about 30 in both cohorts and 32 for. By ROC these values were about 20
      and 24 respectively. According to the other two transitional questions these
      values were for pain 27 and 20 for function. By tertiles the worst the baseline
      score the higher the cut-off values. Percentage of responders does not change
      when comparing responders to the global MCID with their own tertile MCID and were
      about 61% for pain and 50% for function. CONCLUSION: Due to the wide variations,
      MCID estimates should be calculated and used according to the baseline severity
      score.

PMID- 24095838
TI  - Auxin distribution is differentially affected by nitrate in roots of two rice
      cultivars differing in responsiveness to nitrogen.
AB  - BACKGROUND AND AIMS: Although ammonium (NH4(+)) is the preferred form of nitrogen
      over nitrate (NO3(-)) for rice (Oryza sativa), lateral root (LR) growth in roots
      is enhanced by partial NO3(-) nutrition (PNN). The roles of auxin distribution
      and polar transport in LR formation in response to localized NO3(-) availability
      are not known. METHODS: Time-course studies in a split-root experimental system
      were used to investigate LR development patterns, auxin distribution, polar auxin
      transport and expression of auxin transporter genes in LR zones in response to
      localized PNN in 'Nanguang' and 'Elio' rice cultivars, which show high and low
      responsiveness to NO3(-), respectively. Patterns of auxin distribution and the
      effects of polar auxin transport inhibitors were also examined in DR5::GUS
      transgenic plants. KEY RESULTS: Initiation of LRs was enhanced by PNN after 7 d
      cultivation in 'Nanguang' but not in 'Elio'. Auxin concentration in the roots of
      'Nanguang' increased by approx. 24 % after 5 d cultivation with PNN compared with
      NH4(+) as the sole nitrogen source, but no difference was observed in 'Elio'.
      More auxin flux into the LR zone in 'Nanguang' roots was observed in response to
      NO3(-) compared with NH4(+) treatment. A greater number of auxin influx and
      efflux transporter genes showed increased expression in the LR zone in response
      to PNN in 'Nanguang' than in 'Elio'. CONCLUSIONS: The results indicate that
      higher NO3(-) responsiveness is associated with greater auxin accumulation in the
      LR zone and is strongly related to a higher rate of LR initiation in the cultivar
      'Nanguang'.

PMID- 24095839
TI  - The dauer hypothesis and the evolution of parasitism: 20 years on and still going
      strong.
AB  - How any complex trait has evolved is a fascinating question, yet the evolution of
      parasitism among the nematodes is arguably one of the most arresting. How did
      free-living nematodes cross that seemingly insurmountable evolutionary chasm
      between soil dwelling and survival inside another organism? Which of the many
      finely honed responses to the varied and harsh environments of free-living
      nematodes provided the material upon which natural selection could act? Although
      several complementary theories explain this phenomenon, I will focus on the dauer
      hypothesis. The dauer hypothesis posits that the arrested third-stage dauer
      larvae of free-living nematodes such as Caenorhabditis elegans are, due to their
      many physiological similarities with infective third-stage larvae of parasitic
      nematodes, a pre-adaptation to parasitism. If so, then a logical extension of
      this hypothesis is that the molecular pathways which control entry into and
      recovery from dauer formation by free-living nematodes in response to
      environmental cues have been co-opted to control the processes of infective
      larval arrest and activation in parasitic nematodes. The molecular machinery that
      controls dauer entry and exit is present in a wide range of parasitic nematodes.
      However, the developmental outputs of the different pathways are both conserved
      and divergent, not only between populations of C. elegans or between C. elegans
      and parasitic nematodes but also between different species of parasitic
      nematodes. Thus the picture that emerges is more nuanced than originally
      predicted and may provide insights into the evolution of such an interesting and
      complex trait. 

PMID- 24095840
TI  - Long-observation-window band-selective homonuclear decoupling: increased
      sensitivity and resolution in solid-state NMR spectroscopy of proteins.
AB  - Sensitivity and resolution are the two fundamental obstacles to extending solid
      state nuclear magnetic resonance to even larger protein systems. Here, a novel
      long-observation-window band-selective homonuclear decoupling (LOW BASHD) scheme
      is introduced that increases resolution up to a factor of 3 and sensitivity up to
      1.8 by decoupling backbone alpha-carbon (C(alpha)) and carbonyl (C') nuclei in U
      (13)C-labeled proteins during direct (13)C acquisition. This approach introduces
      short (<200 MUs) pulse breaks into much longer (~8 ms) sampling windows to
      efficiently refocus the J-coupling interaction during detection while avoiding
      the deleterious effects on sensitivity inherent in rapid stroboscopic band
      selective homonuclear decoupling techniques. A significant advantage of LOW-BASHD
      detection is that it can be directly incorporated into existing correlation
      methods, as illustrated here for 2D CACO, NCO, and NCA correlation spectroscopy
      applied to the beta1 immunoglobulin binding domain of protein G and 3D CBCACO
      correlation spectroscopy applied to the alpha-subunit of tryptophan synthase.

PMID- 24095841
TI  - Multi-coil magnetic field modeling.
AB  - The performance of multi-coil (MC) magnetic field modeling is compared to
      dedicated wire patterns for the generation of spherical harmonic (SH) shapes as
      these are the workhorse for spatial encoding and magnetic field homogenization in
      MR imaging and spectroscopy. To this end, an example 48 channel MC setup is
      analyzed and shown to be capable of generating all first through fourth order SH
      shapes over small and large regions-of-interest relevant for MR investigations.
      The MC efficiency for the generation of linear gradient fields shares the same
      order of magnitude with classic and state-of-the-art SH gradient coils. MC field
      modeling becomes progressively more efficient with the synthesis of more complex
      field shapes that require the combination of multiple SH terms. The possibility
      of a region-specific optimization of both magnetic field shapes and generation
      performance with the MC approach are discussed with emphasis on the possible
      trade-off between the field accuracy and generation efficiency. MC shimming has
      been shown previously to outperform current SH shimming. Along with the
      efficiency gains of MC shimming shown here, the MC concept has the potential to
      (1) replace conventional shim systems that are based on sets of dedicated SH
      coils and (2) allow optimal object-specific shim solutions similar to object
      specific RF coils. 

PMID- 24095842
TI  - Broadband excitation in solid-state NMR using interleaved DANTE pulse trains with
      N pulses per rotor period.
AB  - We analyze the direct excitation of wide one-dimensional spectra of nuclei with
      spin I=1/2 or 1 in rotating solids submitted to pulse trains in the manner of
      Delays Alternating with Nutations for Tailored Excitation (DANTE), either with
      one short rotor-synchronized pulse of duration taup in each of K rotor periods
      (D1(K)) or with N interleaved equally spaced pulses taup in each rotor period,
      globally also extending over K rotor periods (D(N)(K)). The excitation profile of
      D(N)(K) scheme is a comb of rf-spikelets with Nnu(R)=N/T(R) spacing from the
      carrier frequency, and a width of each spikelet inversely proportional to the
      length, KT(R), of D(N)(K) scheme. Since the individual pulse lengths, taup, are
      typically of a few hundreds of ns, D(N)(K) scheme can readily excite spinning
      sidebands families covering several MHz, provided the rf carrier frequency is
      close enough to the resonance frequency of one the spinning sidebands. If the
      difference of isotropic chemical shifts between distinct chemical sites is less
      than about 1.35/(KT(R)), D(N)(K) scheme can excite the spinning sidebands
      families of several sites. For nuclei with I=1/2, if the homogeneous and
      inhomogeneous decays of coherences during the DANTE sequence are neglected, the K
      pulses of a D1(K) train have a linearly cumulative effect, so that the total
      nutation angle is theta(tot)=K2pinu1taup, where nu1 is the rf-field amplitude.
      This allows obtaining nearly ideal 90 degrees  pulses for excitation or 180
      degrees  rotations for inversion and refocusing across wide MAS spectra
      comprising many spinning sidebands. If one uses interleaved DANTE trains D(N)(K)
      with N>1, only spinning sidebands separated by intervals of Nnu(R) with respect
      to the carrier frequency are observed as if the effective spinning speed was
      Nnu(R). The other sidebands have vanishing intensities because of the
      cancellation of the N contributions with opposite signs. However, the intensities
      of the remaining sidebands obey the same rules as in spectra obtained with nuR.
      With increasing N, the intensities of the non-vanishing sidebands increase, but
      the total intensity integrated over all sidebands decreases. Furthermore, the NK
      pulses in a D(N)(K) train do not have a simple cumulative effect and the optimal
      cumulated flip angle for optimal excitation, theta(tot)(opt)=NK2pinu1taup,
      exceeds 90 degrees . Such D(N)(K) pulse trains allow achieving efficient
      broadband excitation, but they are not recommended for broadband inversion or
      refocusing as they cannot provide proper 180 degrees  rotations. Since D(N)(K)
      pulse trains with N>1 are shorter than basic D1(K) sequences, they are useful for
      broadband excitation in samples with rapid homogeneous or inhomogeneous decay.
      For nuclei with I=1 (e.g., for (14)N), the response to basic D1(K) pulse train is
      moreover affected by inhomogeneous decay due to 2nd-order quadrupole
      interactions, since these are not of rank 2 and therefore cannot be eliminated by
      spinning about the magic angle. For large quadrupole interactions, the signal
      decay produced by second-order quadrupole interaction can be minimized by (i)
      reducing the length of D(N)(K) pulse trains using N>1, (ii) fast spinning, (iii)
      large rf-field, and (iv) using high magnetic fields to reduce the 2nd-order
      quadrupole interaction.

PMID- 24095843
TI  - Modeling neurodegenerative diseases in Caenorhabditis elegans.
AB  - Neurodegenerative diseases which include Alzheimer's disease (AD), Parkinson's
      disease (PD), amyotrophic lateral sclerosis (ALS), Huntington disease (HD), and
      others are becoming an increasing threat to human health worldwide. The
      degeneration and death of certain specific groups of neurons are the hallmarks of
      these diseases. Despite the research progress in identification of several
      disease-related genes, the mechanisms underlying the neurodegeneration in these
      diseases remain unclear. Given the molecular conservation in neuronal signaling
      between Caenorhabditis elegans and vertebrates, an increasing number of research
      scientists have used the nematode to study this group of diseases. This review
      paper will focus on the model system that has been established in C. elegans to
      investigate the pathogenetic roles of those reported disease-related genes in AD,
      PD, ALS, HD and others. The progress in C. elegans provides useful information of
      the genetic interactions and molecular pathways that are critical in the disease
      process, and may help better our understanding of the disease mechanisms and
      search for new therapeutics for these devastating diseases. 

PMID- 24095844
TI  - Global dot integration in typically developing children and in Williams syndrome.
AB  - Williams Syndrome (WS) is a neurodevelopmental disorder that results in deficits
      in visuospatial perception and cognition. The dorsal stream vulnerability
      hypothesis in WS predicts that visual motion processes are more susceptible to
      damage than visual form processes. We asked WS participants and typically
      developing children to detect the global structure Glass patterns, under "static"
      and "dynamic" conditions in order to evaluate this hypothesis. Sequentially
      presented Glass patterns are coined as dynamic because they induce illusory
      motion, which is modeled after the interaction between orientation (form) and
      direction (motion) mechanisms. If the dorsal stream vulnerability holds in WS
      participants, then they should process real and illusory motion atypically.
      However, results are consistent with the idea that form and motion integration
      mechanisms are functionally delayed or attenuated in WS. Form coherence
      thresholds for both static and dynamic Glass patterns in WS were similar to those
      of 4-5year old children, younger than what is predicted by mental age. Dynamic
      presentation of Glass patterns improved thresholds to the same degree as typical
      participants. Motion coherence thresholds in WS were similar to those of mental
      age matches. These data pose constraints on the dorsal vulnerability hypothesis,
      and refine our understanding of the relationship between form and motion
      processing in development. 

PMID- 24095845
TI  - Brief pitch-priming facilitates infants' discrimination of pitch-evoking noise:
      evidence from event-related potentials.
AB  - Pitch is derived by the auditory system through complex spectrotemporal
      processing. Pitch extraction is thought to depend on both spectral cues arising
      from lower harmonics that are resolved by cochlear filters in the inner ear, and
      on temporal cues arising from the pattern of action potentials contained in the
      cochlear output. Adults are capable of extracting pitch in the absence of robust
      spectral cues, taking advantage of the temporal cues that remain. However, recent
      behavioral evidence suggests that infants have difficulty discriminating between
      stimuli with different pitches when resolvable spectral cues are absent. In the
      current experiments, we used the mismatch negativity (MMN) component of the event
      related potential derived from electroencephalographic (EEG) recordings to
      examine a cortical representation of pitch discrimination for iterated rippled
      noise (IRN) stimuli in 4- and 8-month-old infants. IRN stimuli are pitch-evoking
      sounds generated by repeatedly adding a segment of white noise to itself at a
      constant delay. We created IRN stimuli (delays of 5 and 6ms creating pitch
      percepts of 200 and 167Hz) and high-pass filtered them to remove all resolvable
      spectral pitch cues. In experiment 1, we did not find EEG evidence that infants
      could detect the change in the pitch of these IRN stimuli. However, in Experiment
      2, after a brief period of pitch-priming during which we added a sine wave
      component to the IRN stimulus at its perceived pitch, infants did show
      significant MMN in response to pitch changes in the IRN stimuli with sine waves
      removed. This suggests that (1) infants can use temporal cues to process pitch,
      although such processing is not mature and (2) that a short amount of pitch
      priming experience can alter pitch representations in auditory cortex during
      infancy. 

PMID- 24095846
TI  - [Rare hemoglobins in Togo: a 15-year study at the Lome University Campus Hospital
      Center].
AB  - OBJECTIVES: To identify the rare hemoglobins (Hbs) encountered in Togo and
      characterize their geographical and ethnic distribution and hematologic
      expression. MATERIAL AND METHOD: This retrospective descriptive study covers
      27,530 hemoglobin electrophoresis tests performed in the department of Hematology
      of the Lome Campus teaching hospital from January 1996 through December 2010, the
      national reference laboratory. The anomalies identified were studied with both
      alkaline and acid electrophoresis and high performance liquid chromatography
      (HPLC), all performed in Lome. Any other specialized examinations were conducted
      mainly at the biochemistry laboratories of either Robert Debre Hospital in Paris
      or Henri Mondor Hospital in Creteil (France). RESULTS: During the study period,
      20 cases of a rare Hb were identified, i.e., 0.07% of all Hb analyses. These rare
      mutants were: HbK Woolwich (10 cases, 50% of the rare Hbs); HbD Korle-Bu (7
      cases, 35%); HbJ Lome, G Philadelphia, and Hb Lepore (1 case each, 5% for each).
      Eighteen cases were associated with Hb A. Two cases of composite rare Hb were
      found: HbS/HbK Woolwich and HbC/Hb D Korle-Bu. Carriers of Hb Lepore and of
      HbC/HbD Korle-Bu had hypochromic and microcytic anemia. HbK Woolwich was found in
      the Adja-Ewe and Tem-Kabye ethnic groups, in the Maritime and Kara regions; HbD
      Korle-Bu, HbJ Lome, and Hb Lepore were also identified among the Adja-Ewe, and
      HbG Philadelphia in the Akposso ethnic group of the Plateau zone. CONCLUSION:
      This study although limited to Lome, allowed us to identify the rare Hb forms
      observed in Togo. Other studies on a national scale will specify their real
      frequency.

PMID- 24095847
TI  - Slimming starters. Intake of a diet-congruent food reduces meal intake in active
      dieters.
AB  - Dietary restraint is known to break down in the face of tempting foods. Previous
      research suggests exposure to cues associated with slimming such as images or
      odours act as prompts to restrict intake of a tempting snack in dieters. The
      effects of consuming diet-congruent foods on subsequent intake of a meal have not
      yet been investigated. Thus, using a repeated measures design 26 female
      participants (dieters or non-dieters) consumed a diet-congruent (100 kcal salad),
      hedonic (100 kcal garlic bread) or neutral (0 kcal water) preload. A lexical
      decision task measured the salience of diet and hedonic thoughts and participants
      were then offered pizza as a main meal. Appetite sensations were measured
      throughout the study. Compared to the hedonic and neutral preload, a diet
      congruent preload reduced dieters' entire meal intake by 21%. In contrast, non
      dieters consumed 9% more in the hedonic preload condition compared to the neutral
      preload, yet showed no differences between the diet-congruent and other
      conditions. Salad lowered participants desire to eat and increased fullness
      compared to garlic bread and water preloads. Dieters were also less hungry after
      the salad compared to the garlic bread and water preloads. Consuming a diet
      congruent first course may prompt lower intake at a meal, in part due to
      facilitating resolve to refrain from overeating a tempting second course.

PMID- 24095848
TI  - The apolipoprotein B concentration in gingival crevicular fluid increases in
      patients with diabetes mellitus.
AB  - OBJECTIVE: Oral health conditions have a significant relationship with diabetes
      mellitus (DM) as well as dyslipidemia. In this study, we investigated the levels
      of apolipoprotein B (apoB) and oxidized low-density lipoprotein (oxLDL) in the
      gingival crevicular fluid (GCF) from patients with DM. METHODS: GCF and blood
      samples from 18 DM patients and 18 healthy subjects were examined. GCF was
      collected with paper points without inflicting any harm. The apoB and oxLDL
      levels were measured by sandwich ELISA assays. RESULTS: The number of teeth with
      a deep probing pocket depth and the number of teeth with bleeding on probing, two
      typical periodontal parameters, correlated with the DM parameters, such as
      hemoglobin A1c. The GCF volume and the concentrations of protein, apoB and oxLDL
      in GCF were significantly higher in the DM patients than in the healthy subjects.
      In particular, the apoB concentration in GCF was increased 6-fold in the DM
      patients. The GCF apoB concentration correlated well with the DM parameters in
      plasma. CONCLUSION: GCF could be a clinical source for examining not only the
      oral status of patients, but also certain systemic conditions.

PMID- 24095849
TI  - Reprogramming cell death: BCL2 family inhibition in hematological malignancies.
AB  - The BCL2 family members play a central role in regulating programmed cell death
      (apoptosis) and arbitrating the cellular fate through an accurate balance between
      pro-apoptotic (BAX, BAK, and BH3-only proteins) and pro-survival (BCL2 and its
      closest homologues, BCLXL, BCLW and MCL-1) factors. Deregulation of BCL2 family
      proteins contributes to programmed cell death evasion, that is a hallmark of
      human cancers and it is often related to (chemo)therapy resistance. High BCL2
      levels have been detected in most human lymphoid malignancies, not limited to
      follicular lymphoma (where the role of BCL2 overexpression is driven by the
      t[14;18] translocation) but also B-cell chronic lymphocytic leukemia (CLL) and
      multiple myeloma. For all these reasons, the opportunity to induce apoptosis by
      targeting BCL2 proteins is considered a potentially promising therapeutic
      approach in hematological malignancies. BCL2 family inhibition strategies
      currently explored in phase 1, 2 and 3 clinical trials are essentially two: (1)
      the use of antisense-based strategies to knockdown BCL2 or BCLXL expression (e.g.
      oblimersen) or (2) the use of synthetic BH3 mimetics i.e. small molecules binding
      to anti-apoptotic inhibitors thereby allowing the pro-apoptotic activity of BH3
      only molecules (e.g. obatoclax, AT-101, ABT-737 and its derivatives ABT-263 and
      ABT-199). Several of these drugs demonstrated relevant clinical activity as
      single-agent or in combination therapy, with the most significant drawbacks in
      clinical use being represented by challenging pharmacokinetic profile (e.g. iv
      administration, high-levels of plasma proteins binding) and on-target side
      effects (e.g. gastrointestinal toxicity and thrombocytopenia). Further clinical
      development of the current compounds (e.g. ABT-199), showing high efficacy but
      devoid of the most threatening drug-related toxicities, is eagerly awaited.
      Hopefully, in the next future, BCL2 inhibitors (alone or in combination with
      immuno- and/or chemo-therapeutic agents) will represent target-specific drugs
      expanding our therapeutic armamentarium in the fight against hematologic
      malignancies. 

PMID- 24095850
TI  - The associations of oxidized high-density lipoprotein lipids with risk factors
      for atherosclerosis: the Cardiovascular Risk in Young Finns Study.
AB  - Scavenging and reverse transport of atherogenic oxidized lipids by high-density
      lipoprotein (HDL) was recently suggested to contribute to atheroprotection. We
      investigated the associations of oxidized HDL lipids (oxHDLlipids) with known
      risk factors for atherosclerosis in a population-based cross-sectional study of
      1395 Finnish adults ages 24-39 years (54.9% women). Analysis of oxidized lipids
      in isolated HDL and LDL (oxLDLlipids) was based on the determination of
      conjugated dienes. Oxidized LDL was measured also with a method based on
      antibodies against oxidized Apo-B (oxLDLprot). Serum lipids and risk factors were
      measured. In multivariable models, oxHDLlipids were associated inversely with age
      (partial R(2)=2.9% in men, 0.8% in women) and directly with oxLDLlipids (partial
      R(2)=3.4% in men, 4.2% in women) after adjustment for Apo-A1 (partial R(2)=9.6%
      in men, 25.2% in women). In men, oxHDLlipids were also associated inversely with
      insulin (partial R(2)=1.1%). In women, oxHDLlipids were additionally inversely
      associated with waist circumference (partial R(2)=1.8%) and daily smoking
      (partial R(2)=0.7%) and directly with C-reactive protein (CRP; partial R(2)=0.5%)
      and alcohol use (partial R(2)=0.5%). We conclude that an elevated risk profile
      characterized primarily by advanced age is associated with lower oxHDLlipid
      levels in a population of young Finnish men and women. Higher levels of
      oxHDLlipids are additionally associated with higher oxLDLlipid levels. In men,
      higher insulin levels are also associated with lower oxHDLlipid levels. In women,
      increased waist circumference and daily smoking are also associated with lower
      oxHDLlipid levels, and higher CRP levels and alcohol use are associated with
      higher oxHDLlipid levels. 

PMID- 24095851
TI  - Visualizing and quantifying oxidized protein thiols in tissue sections: a
      comparison of dystrophic mdx and normal skeletal mouse muscles.
AB  - Reactive oxygen species (ROS) are not only a cause of oxidative stress in a range
      of disease conditions but are also important regulators of physiological pathways
      in vivo. One mechanism whereby ROS can regulate cell function is by modification
      of proteins through the reversible oxidation of their thiol groups. An
      experimental challenge has been the relative lack of techniques to probe the
      biological significance of protein thiol oxidation in complex multicellular
      tissues and organs. We have developed a sensitive and quantitative fluorescence
      labeling technique to detect and localize protein thiol oxidation in histological
      tissue sections. In our technique, reduced and oxidized protein thiols are
      visualized and quantified on two consecutive tissue sections and the extent of
      protein thiol oxidation is expressed as a percentage of total protein thiols
      (reduced plus oxidized). We tested the application of this new technique using
      muscles of dystrophic (mdx) and wild-type C57Bl/10Scsn (C57) mice. In mdx
      myofibers, protein thiols were consistently more oxidized (19 +/- 3%) compared
      with healthy myofibers (10 +/- 1%) in C57 mice. A striking observation was the
      localization of intensive protein thiol oxidation (70 +/- 9%) within myofibers
      associated with necrotic damage. Oxidative stress is an area of active
      investigation in many fields of research, and this technique provides a useful
      tool for locating and further understanding protein thiol oxidation in normal,
      damaged, and diseased tissues.

PMID- 24095852
TI  - Anthropometric indices and selenium status in British adults: the U.K. National
      Diet and Nutrition Survey.
AB  - Recent studies have raised concern over possible associations between high
      selenium (Se) status and excess adiposity, known to be linked to adverse
      cardiometabolic outcomes. Studies of Se status in relation to adiposity are
      scarce in the United Kingdom. This study examined cross-sectional associations of
      anthropometric indices with Se-status biomarkers in a nationally representative
      sample of 1045 (577 female, 468 male) British Caucasian adults ages 19-64 who
      participated in the 2000-2001 National Diet and Nutrition Survey. Median (first,
      third quartile) values for whole-blood glutathione peroxidase (GPx) activity and
      plasma and erythrocyte Se concentrations were 120.0 (103.0, 142.4) nmol mg Hb(-1)
      min(-1), 1.08 (0.98, 1.20) umol/L, and 1.62 (1.38, 1.91) umol/L, respectively.
      For males, values were 119.0 (100.0, 141.0) nmol mg Hb(-1) min(-1), 1.09 (0.99,
      1.22) umol/L, and 1.54 (1.34, 1.79) umol/L, respectively; for females 121.0
      (105.0, 145.0) nmol mg Hb(-1) min(-1), 1.07 (0.97, 1.18) umol/L, and 1.71 (1.43,
      1.99) umol/L, respectively. Multivariate adjusted mean differences (95% CI) in
      whole-blood GPx between the highest (>30 kg/m(2)) and the lowest (<25 kg/m(2))
      categories of body mass index and the highest (96.5-139.2 cm) and the lowest
      (52.2-78.1cm) quartiles of waist circumference (WC) were -7.9 (-13.2, -2.7) and 
      9.7 (-16.2, -3.2) nmol mg Hb(-1) min(-1), respectively. Difference (95% CI) in
      plasma Se between the third (87.5-96.4 cm) and the lowest quartiles of WC was 
      0.04 (-0.08, -0.03) umol/L. Difference (95% CI) in red blood cell (RBC) Se
      between the highest (0.91-1.11) and the lowest (0.53-0.76) quartiles of waist-to
      hip ratio (WHR) was 0.10 (0.00, 0.20) umol/L. Similar results were observed in
      gender and menopausal-status subgroup analyses. The inverse association between
      plasma Se and WC and the positive association between RBC Se and WHR will need
      confirmation. The findings suggest associations between low whole-blood GPx
      activity and higher measures of general and central adiposity. Further
      experimental and randomized studies are needed to deduce the mechanisms and infer
      causality.

PMID- 24095853
TI  - Grasp posture planning during multi-segment object manipulation tasks -
      interaction between cognitive and biomechanical factors.
AB  - The present study examined adaptations in the planning of initial grasp postures
      during a multi-segment object manipulation task. Participants performed a
      grasping and placing task that consisted of one, two, or three movement segments.
      The position of the targets was manipulated such that the degree of object
      rotation between the home and temporally proximal positions, and between the
      temporally proximal and distal target positions, varied. Participants selected
      initial grasp postures based on the specific requirements of the temporally
      proximal and temporally distal action segments, and adjustments in initial grasp
      posture depended on the temporal order of target location. In addition, during
      the initial stages of the experimental session initial grasp postures were
      influenced to a larger extent by the demands of the temporally proximal segment.
      However, over time, participants overcame these cognitive limitations and
      adjusted their initial grasp postures more strongly to the requirements of the
      temporally distal segment. Taken together, these results indicate that grasp
      posture planning is influenced by cognitive and biomechanical factors, and that
      participants learn to anticipate the task demands of temporally distal task
      demands, which we hypothesize, reduce the burden on the central nervous system. 

PMID- 24095854
TI  - The ultrastructure of the Aedes aegypti heart.
AB  - Comparative structural analyses of the heart and associated tissues in 4th instar
      larvae (L4), pupae and adults of Aedes aegypti were undertaken using a
      combination of microscopy techniques. The Ae. aegypti heart consists of
      cardiomyocytes arranged in a helical fashion, and it is physically associated
      with intersegmental groups of pericardial cells (PCs) and the alary muscles
      (AMs). Ramifications commonly present in AMs are more developed in adults than in
      the immature stages. Pericardial cells absorb and store extracellular components
      as shown by the uptake of carmine dye fed in larval diet. We also observed that
      carmine stained inclusions corresponding to electron-dense structures resembling
      lysosomes that were more abundant and prominent in pupae, suggestive of increase
      of waste accumulation during pupation. The results presented here expand on
      previously known aspects of the mosquito heart and describe for the first time
      comparative aspects of the morphology of the heart in different developmental
      stages. 

PMID- 24095855
TI  - Age assessment based on dental calcification in individuals with Down syndrome.
AB  - It is important to estimate both chronological age (CA) and maturational age of
      an individual, in order to perform orthopedic treatment or surgery, and in cases
      of lost documentation. Use of dental age (DA) for these purposes has been widely
      studied; however, the literature is scarce with regard to individuals with Down
      syndrome (DS), a prevalent condition worldwide. In this study the chronology of
      dental maturation was evaluated by analyzing the DA of individuals with DS based
      on the Chronological Mineralization Table proposed by Nolla (1960). Thus, second
      molars were evaluated in 57 panoramic radiographs of male and female individuals
      with DS, between 5 and 16 years-old. These data were compared with a control
      group of 191 nonsyndromic individuals of the same age group. Correlation between
      CA and DA was ascertained using Pearson's correlation coefficient (r), and the
      difference between these variables was measured using Student's t-test for paired
      samples and the method proposed by Bland and Altman. The difference between DA
      and CA was compared between the control and DS groups using Student's t-test for
      independent samples (alpha=0.05). DA was slightly lower than the CA; however,
      this difference was only significant for females. The difference between DA and
      CA was not significant between individuals with DS and control group (both
      genders, p=0.945; males, p=0.542; females, p=0.381). We concluded that dental
      maturation in individuals with DS occurs similarly to that of nonsyndromic
      individuals. 

PMID- 24095856
TI  - Use of the gait profile score for the evaluation of patients with joint
      hypermobility syndrome/Ehlers-Danlos syndrome hypermobility type.
AB  - Gait analysis (GA) is widely used for clinical evaluations in various
      pathological states, both in children and in adults, such as in patients with
      joint hypermobility syndrome/Ehlers-Danlos syndrome hypermobility type (JHS/EDS
      HT). Otherwise, GA produces a large volume of data and there is the clinical need
      to provide also a quantitative measure of the patient's overall gait. Starting
      from this aim some global indexes were proposed by literature as a summary
      measure of the patient's gait, such as the Gait Profile Score (GPS). While
      validity of the GPS was demonstrated for the evaluation of the functional
      limitation of children with Cerebral Palsy, no studies have been conducted in
      patients JHS/EDS-HT. The aim of our study was therefore to investigate the
      effectiveness of the GPS in the quantification of functional limitation of
      patients with JHS/EDS-HT. Twenty-one adult (age: 36.1 +/- 12.7 years) individuals
      with JHS/EDS-HT were evaluated using GA and from GA data the GPS was computed.
      The results evidenced that the GPS value of patients was 8.9 +/- 2.6,
      statistically different from 4.6 +/- 0.9 displayed by the control group. In
      particular, all values of Gait Variable Scores (GVS) which compose the GPS were
      higher if compared to controls, with the exception of Pelvic Tilt and Foot
      Progression. The correlations between GPS/GVS and Lower Extremity Functional
      Scale (LEFS) showed significant relationship between GPS and the item 11
      ("Walking 2 blocks") (rho=-0.56; p<0.05) and 12 ("Walking a mile") of LEFS (rho=
      0.76; p<0.05). Our results showed that GPS and GVS seem to be appropriate outcome
      measures for the evaluation of the functional limitation during gait of patients
      with JHS/EDS-HT.

PMID- 24095858
TI  - The human specialized DNA polymerases and non-B DNA: vital relationships to
      preserve genome integrity.
AB  - In addition to the canonical right-handed double helix, DNA molecule can adopt
      several other non-B DNA structures. Readily formed in the genome at specific DNA
      repetitive sequences, these secondary conformations present a distinctive
      challenge for progression of DNA replication forks. Impeding normal DNA
      synthesis, cruciforms, hairpins, H DNA, Z DNA and G4 DNA considerably impact the
      genome stability and in some instances play a causal role in disease development.
      Along with previously discovered dedicated DNA helicases, the specialized DNA
      polymerases emerge as major actors performing DNA synthesis through these
      distorted impediments. In their new role, they are facilitating DNA synthesis on
      replication stalling sites formed by non-B DNA structures and thereby helping the
      completion of DNA replication, a process otherwise crucial for preserving genome
      integrity and concluding normal cell division. This review summarizes the
      evidence gathered describing the function of specialized DNA polymerases in
      replicating DNA through non-B DNA structures. 

PMID- 24095857
TI  - The antiviral activities of ISG15.
AB  - Post-translational protein modification is an important strategy for the
      regulation of the cell proteome independent of the need for new gene expression.
      Ubiquitin and ubiquitin-like modifiers mediate the regulation of protein levels,
      signaling pathways, vesicular trafficking, and many other cellular processes
      through their covalent conjugation to proteins. Interferon stimulated gene 15
      (ISG15) is a ubiquitin-like modifier induced by type I interferon. In addition to
      conjugating to potentially hundreds of target proteins, ISG15 can be found in an
      unconjugated form both inside of the cell and released from interferon stimulated
      cells into the extracellular environment. Due to its robust expression after type
      I interferon stimulation and the broad panel of proteins that it targets, ISG15
      has drawn much attention as a potential regulator of the immune response and has
      been shown to mediate protection in a number of different viral infection models.
      Here we will review the current state of the field of ISG15, the viruses against
      which ISG15 mediates protection, and the mechanisms by which ISG15 exerts
      antiviral activity. 

PMID- 24095859
TI  - From simple bacterial and archaeal replicons to replication N/U-domains.
AB  - The Replicon Theory proposed 50 years ago has proven to apply for replicons of
      the three domains of life. Here, we review our knowledge of genome organization
      into single and multiple replicons in bacteria, archaea and eukarya. Bacterial
      and archaeal replicator/initiator systems are quite specific and efficient,
      whereas eukaryotic replicons show degenerate specificity and efficiency, allowing
      for complex regulation of origin firing time. We expand on recent evidence that
      ~50% of the human genome is organized as ~1,500 megabase-sized replication
      domains with a characteristic parabolic (U-shaped) replication timing profile and
      linear (N-shaped) gradient of replication fork polarity. These N/U-domains
      correspond to self-interacting segments of the chromatin fiber bordered by open
      chromatin zones and replicate by cascades of origin firing initiating at their
      borders and propagating to their center, possibly by fork-stimulated initiation.
      The conserved occurrence of this replication pattern in the germline of mammals
      has resulted over evolutionary times in the formation of megabase-sized domains
      with an N-shaped nucleotide compositional skew profile due to replication
      associated mutational asymmetries. Overall, these results reveal an
      evolutionarily conserved but developmentally plastic organization of replication
      that is driving mammalian genome evolution.

PMID- 24095860
TI  - Specification of DNA replication origins and genomic base composition in fission
      yeasts.
AB  - In the "Replicon Theory", Jacob, Brenner and Cuzin proposed the existence of
      replicators and initiators as the two major actors in DNA replication. Over the
      years, many protein components of initiators have been shown to be conserved in
      different organisms during evolution. By contrast, replicator DNA sequences
      (often referred to as replication origins) have diverged beyond possible
      comparison between eukaryotic genomes. Replication origins in the fission yeast
      Schizosaccharomyces pombe are made up of A+T-rich sequences that do not share any
      consensus elements. The information encoded in these replicators is interpreted
      by the Orc4 subunit of the ORC (origin recognition complex), which is unique
      among eukaryotes in that it contains a large domain harboring nine AT-hook
      subdomains that target ORC to a great variety of A+T-rich sequences along the
      chromosomes. Recently, the genomes of other Schizosaccharomyces species have been
      sequenced and the regions encompassing their replication origins have been
      identified. DNA sequence analysis and comparison of the organization of their
      Orc4 proteins have revealed species-specific differences that contribute to our
      understanding of how the specification of replication origins has evolved during
      the phylogenetic divergence of fission yeasts. 

PMID- 24095861
TI  - N-acetylcysteine protects against fluoride-induced oxidative damage in primary
      rat hepatocytes.
AB  - Fluoride induces the overproduction of free radicals, which might in turn affect
      various biochemical parameters. Therefore, the aim of this study was to elucidate
      the role of N-acetylcysteine (NAC) in decreasing fluoride-induced oxidative
      stress. The fluoride intoxicated (0.002; 0.082; 0.164mmol/l) rat hepatocytes was
      pre-treated (60min) and simultaneously treated with NAC (1mmol/l). The resulting
      levels of lactate dehydrogenase (LDH), superoxide dismutase (SOD), glutathione
      peroxidase (GPx), glutathione reductase (GR) and intracellular reduced
      glutathione (GSH) were measured along with the total antioxidant status (TAS) to
      determine whether NAC treatment reduced cell damage and/or the antioxidant state.
      These results suggest that NAC pre-treatment provides protection against fluoride
      induced oxidative stress in hepatocytes. 

PMID- 24095862
TI  - Way forward in case of a false positive in vitro genotoxicity result for a
      cosmetic substance?
AB  - The currently used regulatory in vitro mutagenicity/genotoxicity test battery has
      a high sensitivity for detecting genotoxicants, but it suffers from a large
      number of irrelevant positive results (i.e. low specificity) thereby imposing the
      need for additional follow-up by in vitro and/or in vivo genotoxicity tests. This
      could have a major impact on the cosmetic industry in Europe, seen the imposed
      animal testing and marketing bans on cosmetics and their ingredients. Afflicted,
      but safe substances could therefore be lost. Using the example of triclosan, a
      cosmetic preservative, we describe here the potential applicability of a human
      toxicogenomics-based in vitro assay as a potential mechanistically based follow
      up test for positive in vitro genotoxicity results. Triclosan shows a positive in
      vitro chromosomal aberration test, but is negative during in vivo follow-up
      tests. Toxicogenomics analysis unequivocally shows that triclosan is identified
      as a compound acting through non-DNA reactive mechanisms. This proof-of-principle
      study illustrates the potential of genome-wide transcriptomics data in
      combination with in vitro experimentation as a possible weight-of-evidence follow
      up approach for de-risking a positive outcome in a standard
      mutagenicity/genotoxicity battery. As such a substantial number of cosmetic
      compounds wrongly identified as genotoxicants could be saved for the future. 

PMID- 24095863
TI  - Nicotine increases survival in human colon cancer cells treated with
      chemotherapeutic drugs.
AB  - Cigarette smoking is implicated in the development of colon cancer. Furthermore,
      nicotine increases cell proliferation and inhibits apoptosis through alpha7
      nicotinic acetylcholine receptor (alpha7-nAChR) activation in human colon
      carcinoma cells. An open issue is whether nicotine interfere with colorectal
      cancer pharmacological treatment, by inhibiting drug-mediated apoptosis. To
      assess this hypothesis, we evaluated nicotine effect on Caco-2 and HCT-8 colon
      cancer cells, treated with 5-Fluorouracil (5-FU) and Camptothecin (CPT),
      chemotherapeutics commonly utilized as adjuvant treatment of colon cancer.
      Nicotine decreased anti-proliferative and pro-apoptotic effects exerted by
      chemotherapeutics on both cell lines. These effects partially reverted by
      exposure to alpha-bungarotoxin (alpha-BTX), an inhibitor of alpha7-nAChR.
      Nicotine addition to Caco-2 and HCT-8, treated with 5-FU or CPT, decreased the
      cleavage of substrate of caspase 3 and 7, poly-ADP-ribose polymerase (PARP).
      Moreover, P-ERK/ERK ratio was modified by nicotine addition to 5-FU and CPT
      treated cells in an opposite manner. However, when co-administrating PD98059, an
      ERK phosphorylation inhibitor, an increased apoptosis was observed. In Caco-2 and
      HCT-8 nicotine reverted 5-FU and CPT apoptotic effects through AKT
      phosphorylation, as demonstrated by apoptotic increase in presence of LY294002,
      an AKT phosphorylation inhibitor. Nicotine interfered with colorectal cancer
      pharmacological treatment in vitro by inhibiting apoptosis induced by
      chemotherapeutic drugs. Nicotine anti-apoptotic effects were exerted through ERK
      and AKT pathway activation. 

PMID- 24095864
TI  - Total gastrectomy may result in reduced drug effectiveness due to an increase in
      the expression of the drug-metabolizing enzyme Cytochrome P450, in the liver.
AB  - In patients with gastrectomy, it is possible that drug effectiveness is reduced
      compared to healthy subjects due to the increased of the drug-metabolizing
      enzyme, Cytochrome P450 (CYP). The purpose of this study is to verify this
      possibility. Gastrectomy model mice were prepared to evaluate the expression
      level of various CYPs in the liver from 2 to 24 weeks post-operation. No
      significant differences were observed in the protein expression levels of CYP3A,
      CYP1A, CYP2C, and CYP2D between the sham operation group and the gastrectomy
      group up to 4 weeks after the gastrectomy. On the other hand, significant
      increases in the protein expression levels of any CYPs were observed in the
      gastrectomy group compared to the sham operation group from 12 weeks after the
      gastrectomy onward. These increases in expression levels were maintained until 24
      weeks after the gastrectomy. The examination of metabolic activity in the liver
      in the gastrectomy group using triazolam revealed that the metabolic activity at
      12 weeks after the gastrectomy was significantly increased in the gastrectomy
      group. The administration of the anticancer drug imatinib, which is a substrate
      of CYP3A, to mice at 12weeks after gastrectomy resulted in an increase in the
      metabolic rate, suggesting a possible decrease in drug effectiveness. It has been
      revealed that drug effectiveness may be reduced after gastrectomy because the
      expression levels of various CYPs in the liver were increased over a prolonged
      period. The results of this study can serve as valuable fundamental knowledge for
      drug therapy in patients with gastrectomy.

PMID- 24095865
TI  - A dynamic system for the simulation of fasting luminal pH-gradients using
      hydrogen carbonate buffers for dissolution testing of ionisable compounds.
AB  - The hydrogen carbonate buffer is considered as the most biorelevant buffer system
      for the simulation of intestinal conditions and covers the physiological pH range
      of the luminal fluids from pH 5.5 to about pH 8.4. The pH value of a hydrogen
      carbonate buffer is the result of a complex and dynamic interplay of the
      concentration of hydrogen carbonate ions, carbonic acid, the concentration of
      dissolved and solvated carbon dioxide and its partial pressure above the
      solution. The complex equilibrium between the different ions results in a
      thermodynamic instability of hydrogen carbonate solutions. In order to use
      hydrogen carbonate buffers with pH gradients in the physiological range and with
      the dynamics observed in vivo without changing the ionic strength of the
      solution, we developed a device (pHysio-grad(r)) that provides both acidification
      of the dissolution medium by microcomputer controlled carbon dioxide influx and
      alkalisation by degassing. This enables a continuous pH control and adjustment
      during dissolution of ionisable compounds. The results of the pH adjustment
      indicate that the system can compensate even rapid pH changes after addition of a
      basic or acidic moiety in amounts corresponding up to 90% of the overall buffer
      capacity. The results of the dissolution tests performed for a model formulation
      containing ionizable compounds (Nexium 20mg mups) indicate that both the
      simulated fasting intraluminal pH-profiles and the buffer species can
      significantly affect the dissolution process by changing the lag time prior to
      initial drug release and the release rate of the model compound. A prediction of
      the in vivo release behaviour of this formulation is thus most likely strongly
      related to the test conditions such as pH and buffer species. 

PMID- 24095866
TI  - FoxP3+ regulatory T cells are not important for rotavirus clearance or the early
      antibody response to rotavirus.
AB  - Regulatory T cells produce TGF-beta that contributes to IgA induction by
      intestinal commensal bacteria but their importance in IgA responses to pathogens
      has not been determined. Immunity against the enteropathogen, rotavirus, is
      dependent on intestinal IgA, but whether FoxP3(+) regulatory T cells contribute
      to this IgA is unknown. Infection with rotavirus increased the numbers of
      intestinal FoxP3(+) regulatory T cells. Depletion of FoxP3(+) regulatory T cells
      altered leukocyte activation but did not significantly alter rotavirus clearance
      or specific antibody levels. These data suggest FoxP3(+) regulatory T cells are
      not critical for the early antibody response to rotavirus infection. 

PMID- 24095867
TI  - Induction of human defensins by intestinal Caco-2 cells after interactions with
      opportunistic Candida species.
AB  - In this study we investigated the effects of Candida albicans, Candida krusei,
      Candida tropicalis and Candida parapsilosis on human beta-defensin 2 (HBD-2)
      production in Caco-2 intestinal cell line, and the production of alpha-defensins
      (human neutrophil peptides, HNP 1-3) in peripheral blood. Opportunistic pathogen
      yeasts can modulate the host immune function by inducing defensins, the natural
      antimicrobial peptides. Here we show that Candida spp. stimulated HBD-2
      expression in and release from Caco-2 cells, with C. albicans inducing the
      highest levels of HBD-2. Similarly, HNP 1-3 secretion was significantly increased
      in whole blood after exposure to Candida yeast cells, with C. albicans producing
      the greatest effect. Our investigations underscore the important role of beta and
      alpha defensins produced by intestinal epithelial cells locally and neutrophils
      systemically in the antifungal defense against Candida. 

PMID- 24095868
TI  - cGMP-dependent protein kinase (PKG) mediates the anticontractile capacity of
      perivascular adipose tissue.
AB  - AIM: The aim of this study was to investigate the role of cGMP-dependent protein
      kinase (PKG) in mediating the anticontractile function of perivascular adipose
      tissue (PVAT) and whether its activation can rescue PVAT activity which is lost
      in an experimental model of inflammation. METHODS AND RESULTS: Contractile
      responses to norepinephrine were assessed using wire myography from small
      arterial segments obtained from PKG(-/-), PKG(+/+), adipo(-/-), and C57Bl6/J mice
      with and without PVAT during normal oxygenation and hypoxia. An anticontractile
      effect of PVAT was observed in control blood vessels. This was not present in
      arteries from PKG(-/-) or PKG(+/+) with inhibition of PKG signalling using DT
      2/ODQ. Hypoxia-induced loss of PVAT function was rescued by ANP activation of PKG
      as there was no effect in blood vessels from PKG(-/-) mice or in the presence of
      DT-2. Solution transfer studies demonstrated that PKG was necessary for the
      normal paracrine effects of PVAT on smooth muscle and endothelium. PKG activation
      by atrial natriuretic peptide (ANP) did not restore the absent PVAT
      anticontractile capacity in arteries from adiponectin(-/-) mice; however,
      inhibition of PKG did not further abrogate this effect suggesting dysregulation
      of PKG signalling pathways in this model. The absence of PKG was associated with
      reduced adipocyte adiponectin expression. CONCLUSION: PKG plays a key role in
      regulating normal PVAT function both in modulating anticontractile factor release
      from adipocytes as well as being essential for its downstream dilator function in
      arterial smooth muscle.

PMID- 24095869
TI  - Hypoxia-inducible factor 1-induced G protein-coupled receptor 35 expression is an
      early marker of progressive cardiac remodelling.
AB  - AIMS: G protein-coupled receptor 35 (GPR35) has been characterized to be one of
      the genes that are up-regulated in human heart failure. Since mechanisms
      controlling GPR35 expression are not known, we investigated the regulation of
      GPR35 gene and protein expression in cardiac myocytes and in the mouse models of
      cardiac failure. METHODS AND RESULTS: In cardiac myocytes, GPR35 gene expression
      was found to be exceptionally sensitive to hypoxia and induced by hypoxia
      inducible factor-1 (HIF-1) activation. HIF-1-dependent regulation was established
      by genetic (HIF-1/VP16, Inhibitory Per/Arnt/Sim domain protein) and chemical
      [desferrioxamine (DFO)] modulation of the HIF-1 pathway and further confirmed by
      mutation analysis of the GPR35 promoter and by demonstrating direct binding of
      endogenous HIF-1 to the gene promoter. Hypoxia increased the number and density
      of GPR35 receptors on the cardiomyocyte cell membranes. Chemical GPR35 agonist
      Zaprinast caused GPR35 activation and receptor internalization in cardiac
      myocytes. In addition, overexpressed GPR35 disrupted actin cytoskeleton
      arrangement and caused morphological changes in cultured cardiomyocytes. GPR35
      gene and protein expressions were also induced in mouse models of cardiac
      failure; the acute phase of myocardial infarction and during the compensatory and
      decompensatory phase of pressure-load induced cardiac hypertrophy. CONCLUSIONS:
      Cardiac expression of GPR35 is regulated by hypoxia through activation of HIF-1.
      The expression of GPR35 in mouse models of cardiac infarction and pressure load
      suggests that GPR35 could be used as an early marker of progressive cardiac
      failure.

PMID- 24095870
TI  - Entry of a cationic lytic-type peptide into the cytoplasm via endocytosis
      dependent and -independent pathways in human glioma U251 cells.
AB  - Cationic lytic-type peptides have been studied for clinical application in
      various infections and cancers. This study aimed to determine the functions of
      our specially designed lytic peptide. To investigate the functional mechanism at
      the cell membrane level, we used giant unilayer vesicles (GUVs) mimicking cell
      membranes. In GUVs treated with FITC-labeled lytic peptide (lytic-FITC),
      fluorescence increased in a time-dependent manner. However, no inner fluorescence
      was detected in GUVs treated with lytic peptide and calcein. Next, distribution
      of lytic-FITC peptide on the cell membrane and in the cytoplasm was examined in a
      living human glioma U251 cell line. In the immunocytochemical study, some lytic
      peptide stains colocalized with early endosome antigen protein 1 (EEA-1). In
      cells treated with lytic peptide, the immunofluorescence intensity of lytic
      peptide increased in a concentration and treatment time-dependent manner.
      Cytotoxic activity of lytic peptide decreased after pretreatment with the
      endocytosis inhibitors cytochalasin D, chlorpromazine and amiloride. These
      findings suggest that lytic peptide exerts cytotoxic activity after cellular
      uptake via an endocytosis pathway. In conclusion, the influx mechanism of lytic
      peptide was shown to include not only disintegration and pore formation at the
      cell membrane, but also cell entry via endocytosis dependent and independent
      pathways. 

PMID- 24095871
TI  - HPLC method development for determination of doxycycline in human seminal fluid.
AB  - The present paper reports the development and validation of an analytical method
      for doxycycline quantification in human seminal fluid by HPLC with UV detection.
      The separation of doxycycline was achieved at 40 degrees C on a reversed-phase
      C18 column using isocratic elution. The mobile phase consisted of acetonitrile
      (A) and water buffered at pH 2.5 with a concentrated orthophosphoric acid (B) in
      the volume ratio of 20:80 (v/v), respectively. The detection was performed at
      350nm. As an internal standard (IS), tetracycline was used. The proposed method
      involves the extraction of doxycycline from seminal fluid based on acidic
      precipitation of the proteins using perchloric acid. The method showed good intra
      and inter-day precisions (RSD<7.0%), good accuracy (recovery for
      doxycycline>80%), and high correlation coefficient (r=0.998) for standards
      subjected to the entire procedure. The detection and quantification limits were
      0.087MUg/ml and 0.264MUg/ml. The developed method was used to analyze doxycycline
      in the seminal fluids obtained from male subjects who were treated with
      doxycycline-hyclate. The mean doxycycline concentrations of 0.89+/-0.07MUg/ml and
      0.45+/-0.26MUg/ml were detected in seminal fluid after 6h and 12h, respectively.
      This is the first study reporting extraction and HPLC determination of
      doxycycline in this complex sample and can be very useful in support of clinical
      and pharmacokinetic studies on this antibiotic. 

PMID- 24095873
TI  - Simultaneous determination of homocysteine and asymmetric dimethylarginine in
      human urine by liquid chromatography-tandem mass spectrometry.
AB  - Increased circulating concentrations of homocysteine (HCY) and asymmetric
      dimethylarginine (ADMA) are associated with vascular disease and vascular risk
      factors. HCY has been shown to inhibit the activity of endothelial
      dimethylaminohydrolase (DDAH), causing the accumulation of ADMA and the
      inhibition of nitric oxide synthesis. The concentrations of HCY and ADMA in
      biological fluids are used in the clinical diagnosis of cardiovascular diseases
      and this necessitates the development of a rapid and sensitive method for
      simultaneous determination of HCY and ADMA. A rapid, simple and sensitive method
      for simultaneous determination of HCY and ADMA by liquid chromatography-tandem
      mass spectrometry (LC-MS/MS) coupled with electro spray ionization (ESI) in human
      urine was reported here. The methodology designed here was used to estimate these
      molecules in urine samples collected from patients reported to Cardiology
      Department of our hospital. Chromatographic separation was performed on Atlantis
      HILIC silica (100mm*2.1mm, 5MUm, Waters). Positive multiple reactions monitoring
      (MRM) mode was chosen for quantification of each analyte and cystamine
      dihydrochloride (CYA) was used as the internal standard (IS) for the assay. The
      intra-assay precision and accuracy were in the range of 2.4-4.8 and -1.8% to
      3.1%, respectively. The inter-assay precision and accuracy were in the range of
      3.0-4.2% and -1.2% to 3.2%, respectively. The recoveries were between 94.9% and
      101.4%. Our approach is simple, rapid and could be extended to routine urine
      assay. 

PMID- 24095872
TI  - High-sensitivity analysis of buprenorphine, norbuprenorphine, buprenorphine
      glucuronide, and norbuprenorphine glucuronide in plasma and urine by liquid
      chromatography-mass spectrometry.
AB  - A new method using ultra-fast liquid chromatography and tandem mass spectrometry
      (UFLC-MS/MS) was developed for the simultaneous determination of buprenorphine
      and the metabolites norbuprenorphine, buprenorphine-3beta-glucuronide, and
      norbuprenorphine-3beta-glucuronide in plasma and urine. Sample handling, sample
      preparation and solid-phase extraction procedures were optimized for maximum
      analyte recovery. All four analytes of interest were quantified by positive ion
      electrospray ionization tandem mass spectrometry after solid-phase
      microextraction. The lower limits of quantification in plasma were 1pg/mL for
      buprenorphine and buprenorphine glucuronide, and 10pg/mL for norbuprenorphine and
      norbuprenorphine glucuronide. The lower limits of quantitation in urine were
      10pg/mL for buprenorphine, norbuprenorphine and their glucuronides. Overall
      extraction recoveries ranged from 68-100% in both matrices. Interassay precision
      and accuracy was within 10% for all four analytes in plasma and within 15% in
      urine. The method was applicable to pharmacokinetic studies of low-dose
      buprenorphine. 

PMID- 24095874
TI  - Development and validation of an LC-ESI/MS/MS method with precolumn
      derivatization for the determination of betulin in rat plasma.
AB  - Neutral pentacyclic triterpenes with only one or two hydroxyl groups, such as
      betulin, are not easily ionized by electrospray ionization (ESI). However,
      because betulin is reactive and neutral, derivatization may improve ionization
      efficiency. In the present study, the potency of different derivatization
      reagents was evaluated and p-toluenesulfonyl isocyanate (PTSI) was proven to be
      the optimal. The derivative generated by the reaction of betulin with PTSI was
      ionizable and fragmentable in the negative mode by liquid chromatography
      electrospray ionization/tandem mass spectrometry (LC-ESI/MS/MS). Based on this
      chemical derivatization, an LC-ESI/MS/MS method was developed and validated for
      the quantification of betulin in rat plasma. The sample was extracted with ethyl
      acetate, derivatized with PTSI, separated on an ACQ UPLC BEH phenyl column, and
      analyzed in negative multiple reaction monitoring (MRM) mode. The calibration
      curve was linear over the betulin concentration range 2.5-200ng/mL. The lower
      limit of quantification was 2.5ng/mL. The inter- and intra-day accuracy and
      precision were within +/-15%. Betulin recoveries were 86.7% or higher at three
      quality control levels (5, 50, and 160ng/mL). This validated method was
      subsequently applied to a pharmacokinetic study of betulin in rat plasma after
      oral administration. 

PMID- 24095875
TI  - Binding of modulators to mouse and human multidrug resistance P-glycoprotein. A
      computational study.
AB  - The human multidrug resistance (MDR) P-glycoprotein (P-gp) mediates the extrusion
      of chemotherapeutic drugs from cancer cells. Modulators are relevant
      pharmaceutical targets since they are intended to control or to inhibit its
      pumping activity. In the present work, a common binding site for Rhodamine 123
      and modulators with different modulation activity was found by molecular docking
      over the crystal structure of the mouse P-gp. The modulators involved a family of
      compounds, including derivatives of propafenone (3-phenylpropiophenone nucleus)
      and XR9576 (tariquidar). Our results showed that the relative binding energies
      estimated by molecular docking were in good correlation with the experimental
      activities. Preliminary classical molecular dynamics results on selected P
      gp/modulator complexes were also performed in order to understand the nature of
      the prevalent molecular interactions and the possible main molecular features
      that characterize a modulator. Besides, the results obtained with a human P-gp
      homology model from the mouse structure are also presented and analyzed. Our
      observations suggest that the hydrophobicity and molecular flexibility are the
      main features related to the inhibitory activity. The latter factor would
      increase the modulator ability to fit the aromatic rings inside the transmembrane
      domain. 

PMID- 24095876
TI  - Probing the influence of solvent effect on the lithium ion binding affinity of 12
      crown-O3N derivatives with unsaturated side arms: a computational study.
AB  - Molecular structures of crown ether derivatives play a crucial role in complexing
      and transporting alkali metal ions such as lithium ion. The complexation of such
      ions take place in solution, hence it is important to examine the complexation
      behavior of host systems in solution. We have investigated employing quantum
      chemical calculations the stable conformations of 12-crown-O3N derivatives with
      unsaturated side-arms and its corresponding Li(+) ion complexation in low polar
      to high polar solvent medium. The General Gradient Approximation (GGA) using PW91
      functional with DNP basis set calculated results show that the side-arms
      contribute via cation-pi interaction in the complexation of lithium ion with the
      receptor molecules 2 and 3 quite effectively in the gas phase and in low polar
      solvent medium (CHCl3). The vinyl and acetylene groups attached to the receptor
      molecules are away from the cavity of the crown ether, however, orients toward
      the cavity while complexing with the lithium ion. The auxiliary effect of such
      side-arms to augment the binding affinity of Li(+) ion is reduced in the high
      polar solvent medium. The side-arms also orient away from the complexed Li(+) ion
      in relatively more polar solvents. These calculated results indicate that the
      complexing ability of aza-crowns toward the Li(+) ion can be enhanced with the
      unsaturated side-arms in low polar solvent medium, which however, is less
      effective in more polar mediums. 

PMID- 24095878
TI  - Gene expression in hippocampus as a function of differential trait anxiety levels
      in genetically heterogeneous NIH-HS rats.
AB  - To identify genes involved in the development/expression of anxiety/fear, we
      analyzed the gene expression profile in the hippocampus of genetically
      heterogeneous NIH-HS rats. The NIH-HS rat stock is a unique genetic resource for
      the fine mapping of quantitative trait loci (QTLs) to very small genomic regions,
      due to the high amount of genetic recombinants accumulated along more than 50
      breeding generations, and for the same reason it can be expected that those
      genetically heterogeneous rats should be especially useful for studying
      differential gene expression as a function of anxiety, fearfulness or other
      complex traits. We selected high- and low-anxious NIH-HS rats according to the
      number of avoidance responses they performed in a single 50-trial session of the
      two-way active avoidance task. Rats were also tested in unconditioned
      anxiety/fearfulness tests, i.e. the elevated zero-maze and a "novel-cage
      activity" test. Three weeks after behavioral testing, the hippocampus was
      dissected and prepared for the microarray study. There appeared 29 down-regulated
      and 37 up-regulated SNC-related genes (fold-change>|2.19|, FDR<0.05) in the "Low
      anxious" vs. the "High-anxious" group. Regression analyses (stepwise) revealed
      that differential expression of some genes could be predictive of anxiety/fear
      responses. Among those genes for which the present results suggest a link with
      individual differences in trait anxiety, nine relevant genes (Avpr1b, Accn3,
      Cd74, Ltb, Nrg2, Oprdl1, Slc10a4, Slc5a7 and RT1-EC12), tested for validation
      through qRT-PCR, have either neuroendocrinological or
      neuroinmunological/inflammation-related functions, or have been related with the
      hippocampal cholinergic system, while some of them have also been involved in the
      modulation of anxiety or stress-related (neurobiological and behavioral)
      responses (i.e. Avpr1b, Oprdl1). The present work confirms the usefulness of NIH
      HS rats as a good animal model for research on the neurogenetic basis or
      mechanisms involved in anxiety and/or fear, and suggest that some MHC
      (neuroinmunological/inflammation)-related pathways, as well as the cholinergic
      system within the hippocampus, may play a role in shaping individual differences
      in trait anxiety. 

PMID- 24095877
TI  - Angiotensin II stimulates cardiac fibroblast migration via the differential
      regulation of matrixins and RECK.
AB  - Sustained induction and activation of matrixins (matrix metalloproteinases or
      MMPs), and the destruction and deposition of extracellular matrix (ECM), are the
      hallmarks of cardiac fibrosis. The reversion-inducing-cysteine-rich protein with
      Kazal motifs (RECK) is a unique membrane-anchored endogenous MMP regulator. We
      hypothesized that elevated angiotensin II (Ang II), which is associated with
      fibrosis in the heart, differentially regulates MMPs and RECK both in vivo and in
      vitro. Continuous infusion of Ang II into male C57Bl/6 mice for 2weeks resulted
      in cardiac fibrosis, with increased expressions of MMPs 2, 7, 9 and 14, and of
      collagens Ia1 and IIIa1. The expression of RECK, however, was markedly
      suppressed. These effects were inhibited by co-treatment with the Ang II type 1
      receptor (AT1) antagonist losartan. In vitro, Ang II suppressed RECK expression
      in adult mouse cardiac fibroblasts (CF) via AT1/Nox4-dependent ERK/Sp1
      activation, but induced MMPs 2, 14 and 9 via NF-kappaB, AP-1 and/or Sp1
      activation. Further, while forced expression of RECK inhibits, its knockdown
      potentiates Ang II-induced CF migration. Notably, RECK overexpression reduced Ang
      II-induced MMPs 2, 9 and 14 activation, but enhanced collagens Ia1 and IIIa1
      expression and soluble collagen release. These results demonstrate for the first
      time that Ang II suppresses RECK, but induces MMPs both in vivo and in vitro, and
      RECK overexpression blunts Ang II-induced MMP activation and CF migration in
      vitro. Strategies that upregulate RECK expression in vivo have the potential to
      attenuate sustained MMP expression, and blunt fibrosis and adverse remodeling in
      hypertensive heart diseases. 

PMID- 24095879
TI  - Different MK-801 administration schedules induce mild to severe learning
      impairments in an operant conditioning task: role of buspirone and risperidone in
      ameliorating these cognitive deficits.
AB  - Blockade of N-methyl-d-aspartate receptor (NMDA) by the noncompetitive NMDA
      receptor (NMDAR) antagonist MK-801 produces behavioral abnormalities and
      alterations in prefrontal cortex (PFC) functioning. Due to the critical role of
      the PFC in operant conditioning task learning, we evaluated the effects of acute,
      repeated postnatal injections of MK-801 (0.1mg/kg) on learning performance. We
      injected Long-Evans rats i.p. with MK-801 (0.1mg/kg) using three different
      administration schedules: injection 40 min before beginning the task (during)
      (n=12); injection twice daily for six consecutive days prior to beginning the
      experimental procedures (prior) (n=12); or twice daily subcutaneous injections
      from postnatal day 7 to 11 (postnatal) (n=12). Next, we orally administered
      risperidone (serotonin receptor 2A and dopamine receptor 2 antagonist, 1mg/kg) or
      buspirone (serotonin receptor 1A partial agonist, 10mg/kg) to animals treated
      with the MK-801 schedule described above. The postnatal and prior administration
      schedules produced severe learning deficits, whereas injection of MK-801 just
      before training sessions had only mild effects on acquisition of an operant
      conditioning. Risperidone was able to reverse the detrimental effect of MK-801 in
      the animals that were treated with MK-801 during and prior training sessions. In
      contrast, buspirone was only effective at mitigating the cognitive deficits
      induced by MK-801 when administered during the training procedures. The data
      demonstrates that NMDA antagonism disrupts basic mechanisms of learning in a
      simple PFC-mediated operant conditioning task, and that buspirone and risperidone
      failed to attenuate the learning deficits when NMDA neurotransmission was blocked
      in the early stages of the postnatal period.

PMID- 24095880
TI  - Neuroimaging the temporal dynamics of human avoidance to sustained threat.
AB  - Many forms of human psychopathology are characterized by sustained negative
      emotional responses to threat and chronic behavioral avoidance, implicating
      avoidance as a potential transdiagnostic factor. Evidence from both nonhuman
      neurophysiological and human neuroimaging studies suggests a distributed frontal
      limbic-striatal brain network supports avoidance. However, our understanding of
      the temporal dynamics of the network to sustained threat that prompts sustained
      avoidance is limited. To address this issue, 17 adults were given extensive
      training on a modified free-operant avoidance task in which button pressing
      avoided money loss during a sustained threat period. Subsequently, subjects
      underwent functional magnetic resonance imaging while completing the avoidance
      task. In our regions of interest, we observed phasic, rather than sustained,
      activation during sustained threat in dorsolateral and inferior frontal regions,
      anterior and dorsal cingulate, ventral striatum and regions associated with
      emotion, including the amygdala, insula, substantia nigra and bed nucleus of the
      stria terminalis complex. Moreover, trait levels of experiential avoidance were
      negatively correlated with insula, hippocampal and amygdala activation. These
      findings suggest knowledge that one can consistently avoid aversive outcomes is
      not associated with decreased threat-related responses and that individuals with
      greater experiential avoidance exhibit reduced reactivity to initial threat.
      Implications for understanding brain mechanisms supporting human avoidance and
      psychological theories of avoidance are discussed. 

PMID- 24095881
TI  - Sex- and dose-dependent effects of post-trial calcium channel blockade by
      magnesium chloride on memory for inhibitory avoidance conditioning.
AB  - Calcium influx through voltage-dependent Ca(2+) channels is critical for many
      neuronal processes required for learning and memory. Persistent increases in
      cytosolic intracellular Ca(2+) concentrations in aging neurons are associated
      with learning impairments, while small transient subcellular changes in
      intracellular calcium concentrations play critical roles in neural plasticity in
      young neurons. In the present study, young male and female Fisher 344 * Brown
      Norway (FBN) hybrid rats were administered different doses of magnesium chloride
      (0.0, 100.0, or 200.0mg/kg, i.p.) following a single inhibitory avoidance
      training trial. Extracellular magnesium ions can non-specifically block voltage
      gated calcium channels, and/or reduce the calcium conductance gated via glutamate
      and serine's activation of neuronal NMDA receptors. In our study, magnesium
      chloride dose-dependently enhanced memory compared to controls (significantly
      increased latency to enter a dark compartment previously paired with an aversive
      stimulus) when tested 48 h later as compared to controls. A leftward shift in the
      dose response curve for memory enhancement by magnesium chloride was observed for
      male compared to female rats. These findings provide further insights into
      calcium-dependent modulation of aversive memory, and should be considered when
      assessing the design of effective treatment options for both male and female
      patients with dementia or other memory problems.

PMID- 24095882
TI  - Cochrane re-arranged: support for policies to vaccinate elderly people against
      influenza.
AB  - The 2010 Cochrane review on efficacy, effectiveness and safety of influenza
      vaccination in the elderly by Jefferson et al. covering dozens of clinical
      studies over a period of four decades, confirmed vaccine safety, but found no
      convincing evidence for vaccine effectiveness (VE) against disease thus
      challenging the ongoing efforts to vaccinate the elderly. However, the Cochrane
      review analyzed and presented the data in a way that may itself have hampered the
      desired separation of real vaccine benefits from inevitable 'background noise'.
      The data are arranged in more than one hundred stand-alone meta-analyses,
      according to various vaccine types, study designs, populations, and outcome case
      definitions, and then further subdivided according to virus circulation and
      antigenic match. In this way, general vaccine effects could not be separated from
      an abundance of environmental and operational, non vaccine-related variation.
      Furthermore, expected impacts of changing virus circulation and antigenic drift
      on VE could not be demonstrated. We re-arranged the very same data according to a
      biological and conceptual framework based on the basic sequence of events
      throughout the 'patient journey' (exposure, infection, clinical outcome,
      observation) and using broad outcome definitions and simple frequency
      distributions of VE values. This approach produced meaningful predictions for VE
      against influenza-related fatal and non-fatal complications (average ~30% with
      large dispersion), typical influenza-like illness (~40%), disease with confirmed
      virus infection (~50%), and biological vaccine efficacy against infection (~60%),
      under conditions of virus circulation. We could also demonstrate a VE average
      around zero in the absence of virus circulation, and decreasing VE values with
      decreasing virus circulation and increasing antigenic drift. We regard these
      findings as substantial evidence for the ability of influenza vaccine to reduce
      the risk of influenza infection and influenza-related disease and death in the
      elderly.

PMID- 24095883
TI  - Human papillomavirus (HPV), HPV-associated oropharyngeal cancer, and HPV vaccine
      in the United States--do we need a broader vaccine policy?
AB  - BACKGROUND: Human papillomavirus (HPV) is a sexually transmitted infection (STI)
      of global importance; it is the most prevalent STI in the United States, with
      strains causally linked to oropharyngeal and other cancers. Efforts to prevent
      HPV have been made to varying degrees by policies implemented by different state
      governments; however, HPV and associated oropharyngeal cancer continue to show
      increasing incidence rates in the US. DESIGN: A narrative review based on search
      on SciVerse, PubMed/Medline, Google Scholar, and EMBASE databases, as well as
      literature/documents from the World Health Organization, Centers for Disease
      Control and Prevention, American Cancer Society, National Conference of State
      legislatures, and the U.S. Department of Health and Human Services relevant to
      HPV and HPV vaccine policy in the US. RESULTS: Vaccination has proved to be a
      successful policy in the US, and an extant recommendation aimed at preventing HPV
      and associated cervical and other anogenital cancers is the routine use of HPV
      vaccines for males and females. However, HPV vaccines are presently not
      recommended for preventing oropharyngeal cancer, although they have been shown to
      be highly effective against the HPV strains that are most commonly found in the
      oropharynx. And while there is a history of successful vaccine mandate in the US
      with resulting decrease in occurrence of infectious diseases, implementing HPV
      vaccine mandate has proved to be very unpopular. CONCLUSIONS: With emerging
      evidence of the efficacy of the use of the HPV vaccine in preventing oral-HPV,
      more focus should be put on extending HPV vaccine to present oral HPV infection
      and oropharyngeal cancer. Also, implementing a broader HPV vaccine policy that
      include mandating HPV vaccines as a school-entry requirement for both sexes may
      increase vaccine use in the US for the greater good of the public.

PMID- 24095884
TI  - [Leptospirosis in Libreville (Gabon): four cases].
AB  - OBJECTIVE: Leptospirosis is an endemic disease in tropical countries, where it is
      characterized by clinical polymorphism. We report four cases of leptospirosis
      diagnosed at the military hospital of Libreville (Gabon). CASE REPORTS: Four men
      aged 16 to 31-years-old, were admitted for febrile jaundice, with impaired
      general condition and pain. All lived in disadvantaged neighborhoods in the
      capital. In each case, the laboratory workups found hepatic cytolysis, renal
      failure, hyperleukocytosis, anemia, and an inflammatory state. Serology was
      negative for hepatitis B and C and for HIV, as was testing for malaria. The
      failure to respond to presumptive antimalarial treatment suggested leptospirosis,
      and the diagnosis was confirmed in every case by positive serologies with
      significant antibody titers. The course was quickly favorable under treatment by
      an appropriate antibiotic; liver and kidney function returned to normal within a
      few days. CONCLUSION: In tropical zones, the diagnosis of leptospirosis must be
      considered in all cases of febrile jaundice, especially when liver and kidney
      function are impaired.

PMID- 24095885
TI  - Desflurane/fentanyl compared with sevoflurane/fentanyl on awakening and quality
      of recovery in outpatient surgery using a laryngeal mask airway: a randomized,
      double-blinded controlled trial.
AB  - STUDY OBJECTIVE: To compare time to awakening and upper airway morbidity between
      desflurane and sevoflurane using a Laryngeal Mask Airway (LMA) and a balanced
      anesthetic regimen inclusive of opioids. DESIGN: Randomized, double-blinded,
      placebo-controlled clinical trial. SETTING: Ambulatory surgery unit of a
      university hospital. PATIENTS: 80 subjects receiving general anesthesia for
      outpatient gynecological surgery using a LMA. INTERVENTIONS: Desflurane/fentanyl
      or sevoflurane/fentanyl were used for anesthetic maintenance. MEASUREMENTS:
      Patients were randomly assigned to receive desflurane or sevoflurane. The primary
      outcome was time to awakening as determined by an observer who was blinded to
      study group allocation. Secondary outcomes included the frequency of sore throat,
      cough, and pain perioperatively and at 2 and 24 hours postoperatively. Quality of
      recovery (QoR; via QoR-40 questionnaire) at 24 hours also was determined. MAIN
      RESULTS: The median (IQR) time to eye opening following desflurane was 6.8 (5.0 -
      9.8) minutes versus 11.8 (8.8 - 14.6) minutes following sevoflurane (P < 0.001),
      or a difference of 5.0 (99% CI 2.3 - 6.8) minutes. The median difference in
      response to verbal commands was 5.3 (99% CI 2.4 - 7.1) minutes. The frequency of
      cough, laryngospasm, sore throat, and hoarseness did not differ between groups.
      Quality of recovery at 24 hours was better in the desflurane group: difference in
      medians 6 (99% CI 0 - 12; P = 0.003). CONCLUSIONS: Desflurane retains faster
      awakening properties than does sevoflurane when used in combination with fentanyl
      as part of anesthetic maintenance in outpatient surgery with a LMA. The balanced
      anesthetic maintenance regimen seems to reduce the potential airway reactivity
      properties of desflurane.

PMID- 24095886
TI  - Predictors of desaturation in the postoperative anesthesia care unit: an
      observational study.
AB  - STUDY OBJECTIVE: To evaluate predictors of desaturation and to identify practice
      for patient transport following general anesthesia. DESIGN: Observational quality
      assurance study. SETTING: Postanesthesia Care Unit (PACU) of a university
      affiliated, tertiary-care hospital. PATIENTS: All adult postsurgical patients who
      received general anesthesia and who were admitted to the PACU. MEASUREMENTS:
      Patients were observed over a three-month study period during transfer to the
      PACU with or without oxygen supplementation. Sixteen variables related to
      patient, surgery, and anesthesia were recorded. RESULTS: The study recorded a
      total of 502 PACU admissions. The practice pattern showed that 57% of patients
      were transferred without oxygen and 19% of the entire sample had an initial
      oxygen desaturation of less than 90% on arrival to the PACU. Only 0.8% of
      patients experienced oxygen desaturation when they were transferred with oxygen
      supplementation. After logistic regression analysis, the most significant
      predictor of desaturation was transport without oxygen. CONCLUSIONS: The majority
      of anesthesiologists did not use supplemental oxygen for patient transfer. As a
      result, a higher incidence of postoperative desaturation was noted in their
      patients. Significant predictors of desaturation after general anesthesia
      included patients' sedation score, low respiratory rate, and transport without
      oxygen. The use of oxygen almost completely prevented desaturation during
      transport.

PMID- 24095887
TI  - Effects of postoperative epidural analgesia on recurrence-free and overall
      survival in patients with nonsmall cell lung cancer.
AB  - STUDY OBJECTIVE: To determine whether postoperative epidural analgesia is
      associated with better recurrence-free survival and overall survival after lung
      cancer surgery. DESIGN: Retrospective study. SETTING: Academic hospital.
      MEASUREMENTS: Data of patients with stage 1, stage 2, and stage 3 nonsmall cell
      lung cancer, who underwent tumor resection surgery, were studied. Patient data
      were grouped into three different postoperative pain management interventions:
      intravenous patient-controlled analgesia, patient-controlled epidural analgesia,
      and their combination. Univariate and multicovariate Cox proportional hazards
      models were applied to assess the effects of covariates of interest on overall
      survival and recurrence-free survival. MAIN RESULTS: The type of postoperative
      analgesia used for patients who underwent surgery for nonsmall cell lung cancer
      did not affect recurrence-free survival or overall survival. However, certain
      variables, including age >= 65 years, male gender, body mass index >= 25 kg/m(2),
      ASA physical status 4, and the need for preoperative blood transfusions,
      pneumonectomy, and postoperative radiation, were associated with decreased
      recurrence-free survival and overall survival. CONCLUSIONS: The type of
      postoperative analgesia used after surgery for nonsmall cell lung cancer is not
      associated with better 2-year or 5-year recurrence-free survival or overall
      survival rates.

PMID- 24095888
TI  - Rocuronium-sugammadex use in electroconvulsive therapy of patients with
      pseudocholinesterase enzyme deficiency.

PMID- 24095889
TI  - Effects of aging and propofol on the cardiovascular component of the autonomic
      nervous system.
AB  - STUDY OBJECTIVES: To determine the combined effects of aging and propofol on
      autonomic nervous system activity using heart rate variability (HRV) analysis.
      DESIGN: Prospective, two-parallel group, repeated-measures study. SETTING:
      Operating room of an academic hospital. PATIENTS: ASA physical status 1, 2, and 3
      patients, including 14 young (< 65 yrs) and 14 elderly (> 65 yrs) patients. All
      patients were scheduled for general surgical procedures with general anesthesia.
      INTERVENTIONS: Each patient received two successive propofol doses during
      induction (0.5 mg/kg and 1.5 mg/kg) with a time interval allowing the return of
      Bispectral Index (BIS) to awake values. MEASUREMENTS: Primary outcomes were HRV
      parameters, which included normalized power spectral density at low frequency
      (LFnorm) and high frequency (HFnorm) bands and the ratio LF/HF. Secondary
      outcomes were BIS values, blood pressure, heart rate, respiratory rate, and body
      temperature. MAIN RESULTS: The interaction of age and propofol dose level was
      significant [multivariate analysis of variance, F (3,74) = 4.72, P = 0.005],
      representing a combined effect of age and propofol dose level on the mean HRV
      parameters. Propofol induction decreased the HFnorm component and enhanced LFnorm
      and LF/HF in the younger group, but had no significant effect in the older group.
      Such an effect was not associated with a significant difference in systolic blood
      pressure (SBP) decrements between the younger and older groups. Within each
      group, propofol caused significant decreases in SBP compared with preinduction
      values. Heart rate did not change significantly during propofol administration
      between groups or within groups. CONCLUSIONS: Propofol and aging act in synergy
      to depress the activity of the cardiovascular component of the autonomic nervous
      system. However, a compensatory increase in sympathetic outflow was seen in young
      patients. Such counterbalance was not observed in the older group.

PMID- 24095890
TI  - Reply: To PMID 22301204.

PMID- 24095891
TI  - Correct use of a proper sniff position for laryngoscopy.

PMID- 24095892
TI  - Comparing the novel GlideScope Groove videolaryngoscope with conventional
      videolaryngoscopy: a randomized mannequin study of novice providers.
AB  - STUDY OBJECTIVE: To compare the GlideScope Groove (GG) with conventional
      GlideScope videolaryngoscopy (GVL) and direct laryngoscopy (DL) on intubation
      times, intubation attempts, and glottic visualization of an airway mannequin by
      medical students. DESIGN: Randomized crossover trial. SETTING: Intensive care
      unit of an academic tertiary-care hospital. PARTICIPANTS: 34 medical students
      with no airway management experience. MEASUREMENTS: Each participant received
      standardized video instruction on all three laryngoscopes and was given 10
      minutes to practice with each device. The participants had two attempts using DL,
      and then had two attempts each with either the GG or GVL in random order.
      MEASUREMENTS: Time-to-intubate the mannequin in seconds was recorded. Secondary
      outcomes were Cormack-Lehane grade and number of intubation attempts, also
      recorded. MAIN RESULTS: The median number of seconds required to successfully
      intubate the mannequin with DL, GVL, and GG were 17.4 seconds [interquartile
      range (IQR) 13.2 - 22.1)], 17.7 seconds (IQR 14.9 - 21.0), and 21.7 seconds (IQR
      15.4 - 37.0), respectively. No differences in time-to-intubate was noted among
      the three devices (P = 0.45). A Cormack-Lehane grade 1 view was obtained for 25
      of 34 participants (74%) with DL, 32 of 34 participants (94%) with GVL, and 34 of
      34 participants (100%) with GG. First-attempt intubation success was 30 of 34
      participants (88%) with DL, 34 of 34 participants (100%) with GVL, and 11 of 34
      participants (32%) with GG. Using the GG, 6 of 24 participants (18%) required
      three attempts. More attempts were required for the GG than for DL (P < 0.001) or
      GVL (P < 0.001). CONCLUSIONS: GG was not superior to DL or GVL in time-to
      intubate an airway mannequin.

PMID- 24095893
TI  - Synthesis and in vitro characterization of entirely S-protected thiolated pectin
      for drug delivery.
AB  - The study was aimed to synthesize a thiolated polymer (thiomer) that is resistant
      to oxidation in solutions above pH 5. In order to protect a pectin-cysteine
      conjugate against premature oxidation, the thiomer was S-protected by a disulfide
      connected leaving group. Therefore, 2-mercaptonicotinic acid was first coupled to
      L-cysteine by a disulfide exchange reaction and the purified product was
      subsequently attached to pectin by a carbodiimide mediated amid bond formation.
      The obtained fully S-protected thiolated pectin was in vitro characterized with
      respect to co- and mucoadhesive properties and stability toward oxidation. The
      results indicated a 1.8-fold and 2.3-fold enhanced disintegration time at pH 6.8
      of the S-protected thiolated pectin (Pec-Cys-MNA) compared to thiolated pectin
      (Pec-Cys) and unmodified pectin (Pec). Moreover, rheological measurements of
      polymer/mucus mixtures showed a 1.6-fold (compared to Pec-Cys) and 6.7-fold
      (compared to Pec) increased dynamic viscosity of Pec-Cys-MNA. On the other hand,
      in the presence of a strong oxidizing agent such as H2O2 (0.3% v/v), no increase
      in viscosity of Pec-Cys-MNA could be observed. A 6-month experiment also
      demonstrated the long-term stability of a liquid formulation based on Pec-Cys
      MNA. Further investigations proved that the first time all thiol groups on a
      thiolated polymer could be protected owing to the novel synthesis. Accordingly,
      these features may help to develop thiomer based liquid or gel formulations
      targeting mucosal surfaces such as nasal, ocular or vaginal drug delivery
      systems.

PMID- 24095895
TI  - In vitro-induced cell-mediated immune deviation to encephalitogenic antigens.
AB  - The injection of antigens into the Anterior Chamber (AC) of the eye induces
      Anterior Chamber Associated Immune Deviation (ACAID), which is a potent form of
      immune deviation that is largely attributed to the effect of TGFbeta2 in the
      aqueous humor on ocular antigen-presenting cells (APCs). ACAID antigen
      presentation via APCs and B cells leads to the generation of antigen-specific T
      regulatory cells. The encephalitogenic antigens Myelin oligodendrocyte
      glycoprotein (MOG) and Myelin basic protein (MBP) have an obvious clinical
      relevance. We hypothesized that the intravenous injection of in vitro-generated
      ACAID APCs or in vitro-generated ACAID B cells specific to the encephalitogenic
      antigens MOG35-55/MBP induces specific peripheral tolerance in recipient BALB/c
      mice. We examined the suppression of MOG35-55-specific/MBP-specific inflammatory
      responses using delayed-type hypersensitivity (DTH) assays and Local Adoptive
      Transfer (LAT) assays. Results indicated that MOG35-55-specific/MBP-specific
      tolerance was generated after the intravenous injections of MOG35-55-specific/MBP
      specific ACAID APCs, MOG35-55-specific/MBP-specific ACAID B cells, and MOG35-55
      specific/MBP-specific ACAID T regulatory cells. The specific immune deviation was
      in vitro-induced, cell-mediated, and specific to the encephalitogenic antigens
      MOG35-55/MBP. This in vitro-mediated approach for the generation of MOG35-55/MBP
      specific tolerance opens up avenues for the application of ACAID as a tool for
      the therapy of Multiple Sclerosis, Schizophrenia, and other diseases. 

PMID- 24095894
TI  - Inflammatory dietary pattern and risk of depression among women.
AB  - BACKGROUND: Inflammation is considered as a mechanism leading to depression, but
      the association between inflammatory dietary pattern and depression risk is
      unknown. METHODS: Using reduced-rank regression, we identified a dietary pattern
      that was related to plasma levels of inflammatory markers (C-reactive protein,
      interleukin-6, tumor necrosis factor alpha receptor 2), and we conducted a
      prospective analysis of the relationship of this pattern and depression risk
      among participants in the Nurses' Health Study. A total of 43,685 women (aged 50
      77) without depression at baseline (1996) were included and followed up until
      2008. Diet information was obtained from food frequency questionnaires completed
      between 1984 through 2002 and computed as cumulative average of dietary intakes
      with a 2-year latency applied. We used a strict definition of depression that
      required both self-reported physician-diagnosed depression and use of
      antidepressants, and a broader definition that included women who reported either
      clinical diagnosis or antidepressant use. RESULTS: During the 12-year follow-up,
      we documented 2594 incident cases of depression using the stricter definition and
      6446 using the broader definition. After adjustment for body mass index and other
      potential confounders, relative risks comparing extreme quintiles of the
      inflammatory dietary pattern were 1.41 (95% confidence interval [CI], 1.22, 1.63;
      P-trend<.001) for the strict definition and 1.29 (95% CI, 1.18, 1.41; P
      trend<.001) for the broader definition of depression. CONCLUSIONS: The
      inflammatory dietary pattern is associated with a higher depression risk. This
      finding suggests that chronic inflammation may underlie the association between
      diet and depression.

PMID- 24095896
TI  - Effect of acute and regular exercise on growth hormone secretagogue receptor-1a
      expression in human lymphocytes, T cell subpopulation and monocytes.
AB  - The orexigenic peptide hormone ghrelin exerts potent inhibitory effects on pro
      inflammatory cytokine release via the growth hormone secretagogue receptor-1a
      (GHS-R1a) on T cells and monocytes. As such, ghrelin is a promising therapeutic
      agent for the treatment of inflammatory conditions, but these effects depend on
      the availability of GHS-R1a. The aim of this study was to determine the effect of
      acute exercise on GHS-R1a expression on circulating CD14+ monocytes, total
      lymphocytes and CD3+ T cells. Nine male club-standard cyclists cycled for 1h at
      75% VO2peak (EX) or rested (REST) in a randomised cross-over design. Compared
      with the equivalent times in REST, the concentration of circulating GHS-R1a+
      lymphocytes and monocytes was higher in EX at immediately and 1 and 2h post
      exercise (all p<.05). The concentration of CD3+GHS-R1a+ cells was higher in EX
      than in REST immediately post-exercise only (258 (203)cellsMUl(-1) vs. 62
      (42)cellsMUl(-1), p<.05). Density of GHS-R1a receptor expression was unaffected
      by trial or time. Comparison of active participants at rest with 7 age-, sex- and
      BMI-matched sedentary controls revealed a higher concentration of GHS-R1a+
      lymphocytes in active males (p<.05). These findings suggest a preferential
      recruitment of specific cell subpopulations expressing GHS-R1a into the
      peripheral circulation with acute and regular exercise. Given that the anti
      inflammatory effects of ghrelin depend on the availability of GHS-R1a, the
      preferential recruitment of subpopulations with high anti-inflammatory potential
      found here add a novel aspect to the potential mechanisms by which exercise acts
      to reduce pro-inflammatory cytokine levels. 

PMID- 24095898
TI  - Visualizing compaction of polysomes in bacteria.
AB  - During protein synthesis, many translating ribosomes are bound together with an
      mRNA molecule to form polysomes (or polyribosomes). While the spatial
      organization of bacterial polysomes has been well studied in vitro, little is
      known about how they cluster when cellular conditions are highly constrained. To
      better understand this, we used electron tomography, template matching, and three
      dimensional modeling to analyze the supramolecular network of ribosomes after
      induction of translational pauses. In Escherichia coli, we overexpressed an mRNA
      carrying a polyproline motif known to induce pausing during translation. When
      working with a strain lacking transfer-messenger RNA, the principle actor in the
      "trans-translation" rescuing system, the cells survived the hijacking of the
      translation machinery but this resulted in a sharp modification of the ribosomal
      network. The results of our experiments demonstrate that single ribosomes are
      replaced with large amounts of compacted polysomes. These polysomes are highly
      organized, principally forming hairpins and dimers of hairpins that stack
      together. We propose that these spatial arrangements help maintain translation
      efficiency when the rescue systems are absent or overwhelmed. 

PMID- 24095899
TI  - Patient-specific FE analyses of metatarsal bones with inhomogeneous isotropic
      material properties.
AB  - The mechanical response of human metatarsal bones is of importance in both
      research and clinical practice, especially when associated with the correction of
      Hallux Valgus. Verified and validated patient-specific finite-element analysis
      (FEA) based on CT scans developed for human femurs are extended here to the first
      and second metatarsal bones. Two fresh-frozen metatarsal #1 and five metatarsal
      #2 bones from three donors were loaded in-vitro at three different angles. Holes
      typical to Hallux Valgus correction were then drilled in the bones, which were
      reloaded until fracture. In parallel, high-order FE models of the bones were
      created from CT-scans that mimic the experimental setting. We validated the FE
      results by comparison to experimental observations. Excellent agreement was
      obtained with R(2)=0.97 and slope of the regression line close to 1. We also
      compared the FE predicted fracture load and location for the second metatarsal
      bones with these measured in the experiment, demonstrating an excellent
      prediction within 10% difference. After validation of the FE predictions, they
      were used to investigate the effect of drilled hole position, dimension and the
      insertion of a metallic device on the mechanical response so to optimize the
      outcome of the Hallux Valgus correction. This study further substantiates the
      potential use of FEA in clinical practice. 

PMID- 24095900
TI  - A simple case of drowning?

PMID- 24095897
TI  - Antiviral mechanisms of human defensins.
AB  - Defensins are an effector component of the innate immune system with broad
      antimicrobial activity. Humans express two types of defensins, alpha- and beta
      defensins, which have antiviral activity against both enveloped and non-enveloped
      viruses. The diversity of defensin-sensitive viral species reflects a multitude
      of antiviral mechanisms. These include direct defensin targeting of viral
      envelopes, glycoproteins, and capsids in addition to inhibition of viral fusion
      and post-entry neutralization. Binding and modulation of host cell surface
      receptors and disruption of intracellular signaling by defensins can also inhibit
      viral replication. In addition, defensins can function as chemokines to augment
      and alter adaptive immune responses, revealing an indirect antiviral mechanism.
      Nonetheless, many questions regarding the antiviral activities of defensins
      remain. Although significant mechanistic data are known for alpha-defensins,
      molecular details for beta-defensin inhibition are mostly lacking. Importantly,
      the role of defensin antiviral activity in vivo has not been addressed due to the
      lack of a complete defensin knockout model. Overall, the antiviral activity of
      defensins is well established as are the variety of mechanisms by which defensins
      achieve this inhibition; however, additional research is needed to fully
      understand the role of defensins in viral pathogenesis. 

PMID- 24095901
TI  - Mechanisms of change in cognitive behavioral therapy for panic disorder: the
      unique effects of self-efficacy and anxiety sensitivity.
AB  - The present study examined temporal dependencies of change of panic symptoms and
      two promising mechanisms of change (self-efficacy and anxiety sensitivity) during
      an 11-session course of cognitive-behavior therapy (CBT) for Panic Disorder (PD).
      361 individuals with a principal diagnosis of PD completed measures of self
      efficacy, anxiety sensitivity, and PD symptoms at each session during treatment.
      Effect size analyses indicated that the greatest changes in anxiety sensitivity
      occurred early in treatment, whereas the greatest changes in self-efficacy
      occurred later in treatment. Results of parallel process latent growth curve
      models indicated that changes in self-efficacy and anxiety sensitivity across
      treatment uniquely predicted changes in PD symptoms. Bivariate and multivariate
      latent difference score models indicated, as expected, that changes in anxiety
      sensitivity and self-efficacy temporally preceded changes in panic symptoms, and
      that intraindividual changes in anxiety sensitivity and self-efficacy
      independently predicted subsequent intraindividual changes in panic symptoms.
      These results provide strong evidence that changes in self-efficacy and anxiety
      sensitivity during CBT influence subsequent changes in panic symptoms, and that
      self-efficacy and anxiety sensitivity may therefore be two distinct mechanisms of
      change of CBT for PD that have their greatest impact at different stages of
      treatment. 

PMID- 24095902
TI  - Maturin is a novel protein required for differentiation during primary
      neurogenesis.
AB  - Proliferation and differentiation are tightly controlled during neural
      development. In the embryonic neural plate, primary neurogenesis is driven by the
      proneural pathway. Here we report the characterization of Maturin, a novel,
      evolutionarily conserved protein that is required for normal primary
      neurogenesis. Maturin is detected throughout the early nervous system, yet it is
      most strongly expressed in differentiating neurons of the embryonic fish, frog
      and mouse nervous systems. Maturin expression can be induced by the proneural
      transcription factors Neurog2, Neurod1, and Ebf3. Maturin overexpression promotes
      neurogenesis, while loss-of-function inhibits the differentiation of neuronal
      progenitors, resulting in neural plate expansion. Maturin knockdown blocks the
      ability of Neurog2, Neurod1, and Ebf3 to drive ectopic neurogenesis. Maturin and
      Pak3, are both required for, and can synergize to promote differentiation of the
      primary neurons in vivo. Together, our results suggest that Maturin functions
      during primary neurogenesis and is required for the proneural pathway to regulate
      neural differentiation.

PMID- 24095904
TI  - Metabolic evaluation of urolithiasis and obesity in a midwestern pediatric
      population.
AB  - PURPOSE: The incidence of urolithiasis has been proved to be increasing in the
      adult population, and evidence to date suggests that the same holds true for the
      pediatric population. While adult urolithiasis is clearly linked to obesity,
      studies of pediatric patients have been less conclusive. We hypothesized that a
      population of otherwise healthy children with stones would have an increased body
      mass index compared to a control population, and that obese pediatric stone
      formers would have results on metabolic assessment that are distinct from
      nonobese stone formers. MATERIALS AND METHODS: We retrospectively reviewed the
      charts of all patients 10 to 17 years old with upper tract urolithiasis without
      comorbidities treated between 2006 and 2011. Mean body mass index of our
      population was compared to state data, and 24-hour urine collection results were
      compared between obese and nonobese patients with stones. RESULTS: The obesity
      rate in 117 patients with urolithiasis did not differ significantly from the
      obesity rate derived from the 2007 National Survey of Children's Health
      (observed/expected ratio 1.11, 95% CI 0.54-1.95). Using t-test and chi-square
      comparisons, overall 24-hour urine collection data did not show statistically
      significant differences. CONCLUSIONS: Our results do not confirm obesity as a
      risk factor for pediatric urolithiasis in otherwise healthy patients. We also
      found no substantial metabolic differences between healthy nonobese stone formers
      and obese patients. While the pediatric literature is mixed, our study supports
      the majority of published series that have failed to establish a link between
      pediatric urolithiasis and obesity.

PMID- 24095903
TI  - Scrib is required for epithelial cell identity and prevents epithelial to
      mesenchymal transition in the mouse.
AB  - The integrity and function of epithelial tissues depend on the establishment and
      maintenance of defining characteristics of epithelial cells, cell-cell adhesion
      and cell polarity. Disruption of these characteristics can lead to the loss of
      epithelial identity through a process called epithelial to mesenchymal transition
      (EMT), which can contribute to pathological conditions such as tissue fibrosis
      and invasive cancer. In invertebrates, the epithelial polarity gene scrib plays a
      critical role in establishing and maintaining cell adhesion and polarity. In this
      study we asked if the mouse homolog, Scrib, is required for establishment and/or
      maintenance of epithelial identity in vivo. To do so, we conditionally deleted
      Scrib in the head ectoderm tissue that gives rise to both the ocular lens and the
      corneal epithelium. Deletion of Scrib in the lens resulted in a change in
      epithelial cell shape from cuboidal to flattened and elongated. Early in the
      process, the cell adhesion protein, E-cadherin, and apical polarity protein, ZO
      1, were downregulated and the myofibroblast protein, alphaSMA, was upregulated,
      suggesting EMT was occurring in the Scrib deficient lenses. Correlating
      temporally with the upregulation of alphaSMA, Smad3 and Smad4, TGFbeta signaling
      intermediates, accumulated in the nucleus and Snail, a TGFbeta target and
      transcriptional repressor of the gene encoding E-cadherin, was upregulated. Pax6,
      a lens epithelial transcription factor required to maintain lens epithelial cell
      identity also was downregulated. Loss of Scrib in the corneal epithelium also led
      to molecular changes consistent with EMT, suggesting that the effect of Scrib
      deficiency was not unique to the lens. Together, these data indicate that
      mammalian Scrib is required to maintain epithelial identity and that loss of
      Scrib can culminate in EMT, mediated, at least in part, through TGFbeta
      signaling.

PMID- 24095905
TI  - Impact of folate intake on prostate cancer recurrence following definitive
      therapy: data from CaPSURETM.
AB  - PURPOSE: A randomized, placebo controlled clinical trial of folic acid
      supplementation for the chemoprevention of colorectal adenoma revealed an
      increased incidence of prostate cancer in the treatment group. Limited data exist
      on postdiagnostic folate/folic acid intake and the risk of prostate cancer
      progression. We prospectively examined the association between postdiagnostic
      folate consumption and the risk of prostate cancer recurrence after radical
      prostatectomy, external beam radiation therapy and brachytherapy. MATERIALS AND
      METHODS: This study was done in 1,153 men treated with radical prostatectomy,
      external beam radiation therapy and brachytherapy who had clinical stage T1-T2c
      prostate adenocarcinoma and participated in the CaPSURE Diet and Lifestyle
      substudy by completing the semiquantitative Food Frequency Questionnaire in 2004
      to 2005. We used Cox proportional hazards regression to analyze the association
      between folate intake and prostate cancer progression. RESULTS: Prostate cancer
      progressed in 101 men (8.76%) during a mean 34-month followup. After multivariate
      adjustment we observed no evidence of an association of the intake of total
      folate, dietary folate or dietary folate equivalents with prostate cancer
      recurrence. On secondary analysis by treatment after radical prostatectomy
      patients in the lowest decile of dietary folate intake had a 2.6-fold increase in
      the risk of recurrence (HR 2.56, 95% CI 1.23-5.29, p = 0.01). In patients treated
      with external beam radiation and brachytherapy we observed no evidence of an
      association between prostate cancer progression and increased folate intake.
      CONCLUSIONS: Results suggest that the consumption of foods and multivitamins that
      contain folate is not associated with prostate cancer progression after
      definitive treatment.

PMID- 24095906
TI  - Factors affecting complication rates of percutaneous nephrolithotomy in children:
      results of a multi-institutional retrospective analysis by the Turkish pediatric
      urology society.
AB  - PURPOSE: We assessed factors affecting complication rates of percutaneous
      nephrolithotomy in children. MATERIALS AND METHODS: We retrospectively evaluated
      data on 1,205 renal units in 1,157 children treated with percutaneous
      nephrolithotomy at 16 Turkish centers between 1991 and 2012. Of the patients
      28.3% had a history of urolithiasis. Complications were evaluated according to
      the Satava classification system and modified Clavien grading system. Univariate
      and multivariate analyses were done to determine predictive factors affecting
      complication rates. RESULTS: A total of 515 females and 642 males were studied.
      Mean +/- SD patient age was 8.8 +/- 4.7 years (range 4 months to 17 years). Mean
      +/- SD stone size, operative time and postoperative hospital stay were 4.09 +/-
      4.06 cm(2), 93.5 +/- 48.6 minutes and 5.1 +/- 3.3 days, respectively.
      Postoperative stone-free rate was 81.6%. A total of 359 complications occurred in
      334 renal units (27.7%). Complications were intraoperative in 118 cases and
      postoperative in 241. While univariate analysis revealed that stone history,
      positive urine culture, operative time, length of hospitalization, treatment
      success, punctured calyx and location of the stone significantly affected the
      complication rates (p <0.05), operative time, sheath size, mid calyceal puncture
      and partial staghorn formation were the statistically significant parameters
      affecting complication rates on multivariate logistic regression analysis.
      CONCLUSIONS: Percutaneous nephrolithotomy is the treatment of choice for most
      renal calculi in children. The technique is effective and safe in children, with
      a high success rate and a low rate of major complications. The significant
      factors identified should be considered by clinicians to decrease associated
      complication rates.

PMID- 24095907
TI  - Pediatric nephrectomy: incidence, indications and use of minimally invasive
      techniques.
AB  - PURPOSE: There is a paucity of knowledge regarding nephrectomy in contemporary
      United States pediatric populations. Usage patterns, indications and demographics
      of children undergoing nephrectomy are unknown. Given the significant increases
      in the use of minimally invasive nephrectomy in adults, we hypothesized similar
      trends may be seen in the pediatric population. MATERIALS AND METHODS: An
      estimated total of 27,615 children undergoing nephrectomy between 1998 and 2010
      was extracted from the Nationwide Inpatient Sample. Trends in use were analyzed
      with the estimated annual percent change methodology using linear regression and
      proportions by chi-square. Determinants of minimally invasive nephrectomy were
      evaluated using generalized linear models adjusted for clustering with
      generalized estimating equations. RESULTS: The annual incidence of pediatric
      nephrectomy was 2.90 per 100,000 patient-years and remained stable. Nephrectomy
      was most common in children 0 to 1 year old (36%) and least common in children 6
      to 9 years old (14%). However, nephrectomy for malignancy was most common in
      children 3 to 4 years old. Minimally invasive nephrectomy usage increased from
      1.1% to 11.6% during the study period (estimated annual percent change 72.82%, p
      = 0.007). On multivariable analysis patients with malignancy (OR 0.07, p <0.001)
      had a lower rate of minimally invasive nephrectomy. Increased use was associated
      with increasing age (OR 1.07, p <0.001), treatment at a teaching institution (OR
      1.95, p = 0.008) and increasing hospital volume (OR 1.01, p = 0.001).
      CONCLUSIONS: While the annual incidence of nephrectomy is stable, the use of
      minimally invasive nephrectomy is expanding in the pediatric population. Benign
      pathology and increasing age as well as nephrectomy at high volume teaching
      institutions are independently associated with minimally invasive nephrectomy
      use.

PMID- 24095908
TI  - Adult immunohistochemical markers fail to detect intratubular germ cell neoplasia
      in prepubertal boys with cryptorchidism.
AB  - PURPOSE: Intratubular germ cell neoplasia is a precursor to testicular germ cell
      cancer. The condition is characterized by large germ cells with large nuclei with
      a hyperchromatic, coarse chromatin pattern, large prominent nucleoli and abundant
      pale cytoplasm. In prepubertal boys these cells are located centrally and
      peripherally mixed with normal cells in the seminiferous tubules. We evaluated
      the impact of adult intratubular germ cell neoplasia marking immunohistochemistry
      in screening for intratubular germ cell neoplasia in boys with cryptorchidism.
      MATERIALS AND METHODS: Histology sections of 236 testicular biopsies were
      retrieved from 170 boys 1 month to 15 years old operated on for cryptorchidism
      (excluding disorders of sex development). Specimens were incubated with primary
      antibodies, including anti-placental-like alkaline phosphatase, anti-Oct3/4, anti
      C-kit and anti-D2-40 receptor. RESULTS: A 1-year, 1-month-old boy had
      intratubular germ cell neoplasia and all positive markers. The prevalence of
      placental-like alkaline phosphatase positive staining of germ cells in testicular
      biopsies was 98% in boys younger than 1 year, 82% in those 1 to less than 2 years
      old, 74% in those 2 to less than 3 years old and 60% in those 3 to 15 years.
      Similarly the prevalence of C-kit positive staining was 71% in boys younger than
      1 year, 49% in those 1 to less than 2 years, 16% in those 2 to less than 3 years
      and 34% in those 3 to 15 years. Placental-like alkaline phosphatase negative germ
      cells did not express any of the other described antigens. In none of the 116
      testes from boys older than 1 year and 7 months were any Oct3/4 or D2-40 positive
      germ cells identified. Up to that age 33% and 8% of biopsies were Oct3/4 and D2
      40 positive, respectively. CONCLUSIONS: Adult intratubular germ cell
      neoplasia/cancer immunohistochemical markers cannot be used alone for
      intratubular germ cell neoplasia screening in male infants with cryptorchidism
      because positive immunohistochemistry is commonly seen within this age group,
      when most orchiopexies are performed. It is generally not plausible that
      intratubular germ cell neoplasia originates during fetal development in patients
      with cryptorchidism.

PMID- 24095909
TI  - [Editor's commentary. Selenium].

PMID- 24095910
TI  - [Selenium: its antioxidant effects and issues in selenium supply].
AB  - The author first summarizes briefly the antioxidant effects attributed to
      selenium. Literature data on the selenium supply in Hungary are reviewed in
      detail, also noting some important international reports. Hungarian soils are
      selenium deficient and this is reflected partly in selenium content of the
      plants, too. Selenium supplementation has been generally applied to most
      livestock since the 1980s in Hungary in order to prevent diseases associated with
      selenium deficiency. There are little data on the selenium content of Hungarian
      foodstuffs; therefore, selenium content of important foodstuffs available in the
      European Union is reviewed in detail. Data on selenium concentrations in human
      plasma or serum are scarce, and the results depend substantially on the
      analytical methods applied. In conclusion, Hungary is a country with marginal
      selenium deficiency, and this may play a role in the pathogenesis and poor
      treatment results of several diseases.

PMID- 24095911
TI  - [Significance of selenium in the pathogenesis and therapy of cardiovascular
      diseases and those requiring intensive care].
AB  - Selenium deficiency results in profound changes in cellular defence mechanisms
      against oxidative stress, which plays an important role in the development of
      cardiovascular disease and the associated risk factors. Increased formation and
      decreased elimination of reactive oxygen radicals contribute to the complicated
      mechanisms of sepsis and related disorders. Use of selenium in prevention and
      treatment of the above mentioned conditions is not a new idea, but controversial
      data were published in relation to both fields recently. The aim of the present
      review is to summarize the most important results related to this area.

PMID- 24095912
TI  - [The role of selenium in endocrine system diseases].
AB  - Oxygen derived free radicals, generated by a number of cellular reactions,
      include superoxide anion, hydrogen peroxide and hydroxyl radicals. They exert
      their cytotoxic effects mainly via peroxidation of the cell membrane resulting in
      the loss of membrane integrity. The essential trace element, selenium exerts
      complex effects on the endocrine systems, partly due to its antioxidant capacity.
      Well-characterized selenoproteins include iodothyronine deiodinases, glutathione
      peroxidases and thioredoxin reductases involved in thyroid hormone metabolism and
      protection from oxidative damage. The value of selenium supplementation in
      autoimmune thyroid disorders has been investigated and most studies confirmed the
      beneficial effect of selenium supplementation in Hashimoto's and Graves's
      diseases. Recently, selenium proved to be effective in mild inflammatory
      orbitopathy. There are a number of reports about the effect of selenium in
      diabetes mellitus, but the data are controversial as both insulin-like and
      diabetes-inducing effects of selenium have been described. Selenium was
      successfully used in both female and male infertility of autoimmune origin.

PMID- 24095913
TI  - [The relationship between selenium and gastrointestinal inflammatory diseases].
AB  - The cell-membrane toxicity of reactive oxygen and nitrogen species (RONS) plays
      an increasing role in the pathomechanism of gastrointestinal tract diseases.
      Trace elements are important parts of antioxidant protecting system, especially
      the selenium (Se), which, in the form of glutathione peroxidase contributes to
      the immunity of the gut (GALT). Due to the absorptional disorders and consequent
      malnutrition observed in the course of inflammatory bowel diseases (IBD) an
      important role is associated with nutritional therapy, including energy-, protein
      and trace element-support. Human studies show, that IBD is mostly accompanied by
      lower serum Se concentrations, reduced antoxidant and increased proinflammatory
      activity. Adequate Se-replacement may reduce the severity of organ failure and
      infections, but not mortality. However, it is encouraging that in animal studies
      obvious preventive effect of Se has been found on IBD and chronic inflammation
      induced colon cancer .

PMID- 24095914
TI  - [Importance of selenium homeostasis in chronic and end-stage kidney diseases].
AB  - Selenium is an essential trace element for the human body with a significant
      antioxidant effect. Selenium deficiency and excess are both detrimental for
      proper functioning of the human body. The possible association between selenium
      deficiency and acute or chronic renal disease, along with their complications has
      been less intensively investigated, however, there are firm data showing that
      selenium deficiency and renal failure increase the risk of both coronary artery
      disease and total mortality. Further studies revealed that selenium deficiency
      increases the risk of death due to infection in patients treated with
      hemodialysis through dysfunction of the immune system. However, there are no data
      whether the imbalance of selenium metabolism, especially selenium deficiency,
      could cause chronic kidney disease or renal failure. As far as results of
      selenium measurements, there is convincing evidence that protein loss and renal
      replacement treatment reduce serum selenium levels. Despite some contradictory
      results obtained from various studies regarding selenium deficiency in chronic
      kidney diseases, it seems that selenium supplementation may be beneficial in many
      patients with severe or end-stage kidney disease including those treated with
      dialysis.

PMID- 24095916
TI  - The first genetically confirmed case of Dioctophyme renale (Nematoda:
      Dioctophymatida) in a patient with a subcutaneous nodule.
AB  - We describe a nematode larva in a subcutaneous nodule excised from a 44-year-old
      Chinese male who had been living in Japan for 15 years. Morphological features
      suggested that the worm was a dioctophimatid nematode. PCR amplification and
      sequencing of small subunit ribosomal DNA and mitochondrial cytochrome subunit c
      oxidase genes allowed us to identify the larva as the giant kidney worm,
      Dioctophyme renale (Goeze, 1972). This is the first molecularly confirmed human
      case of a dermal D. renale infection.

PMID- 24095918
TI  - Elucidation of signaling molecules involved in ergosterol perception in tobacco.
AB  - Ergosterol, a principal compound of the fungal plasma membrane, is regarded as a
      pathogen-associated molecular pattern. In the present study, the role of
      salicylic acid (SA), jasmonic acid (JA) and spermine signaling pathways after
      ergosterol elicitation were evaluated. SA, JA and spermine production, as well as
      accumulation of transcripts for a lipoxygenase (NaLOX3) gene, the phenylalanine
      ammonia lyase gene, selected pathogenesis-related genes (PR1, PR5), and
      peroxidase tPOXC1 were determined in tobacco (Nicotiana tabacum L. cv. Xanthi) in
      response to ergosterol elicitation. To understand the sequence of the signaling
      cascade, several representative steps involved in the synthesis of crucial
      signaling molecules were targeted using specific inhibitors. SA signaling
      pathway, together with calmodulin-dependent protein kinases and nitric oxide, was
      demonstrated to play an important role in the induction of defense-related genes
      following ergosterol treatment. The results suggested that nitric oxide
      participates in defense-related gene activation following ergosterol treatment
      but does not directly participate in activation of reactive oxygen species
      production. The induction of PR5 and tPOXC1 transcripts was found to be not fully
      dependent on calmodulin/Ca2+ and SA signaling, contrary to the PR1a transcript. A
      possible candidate for this SA-independent pathway is the spermine pathway, as
      elevated spermine levels were detected following ergosterol treatment.

PMID- 24095919
TI  - Current understanding on ethylene signaling in plants: the influence of nutrient
      availability.
AB  - The plant hormone ethylene is involved in many physiological processes, including
      plant growth, development and senescence. Ethylene also plays a pivotal role in
      plant response or adaptation under biotic and abiotic stress conditions. In
      plants, ethylene production often enhances the tolerance to sub-optimal
      environmental conditions. This role is particularly important from both
      ecological and agricultural point of views. Among the abiotic stresses, the role
      of ethylene in plants under nutrient stress conditions has not been completely
      investigated. In literature few reports are available on the interaction among
      ethylene and macro- or micro-nutrients. However, the published works clearly
      demonstrated that several mineral nutrients largely affect ethylene biosynthesis
      and perception with a strong influence on plant physiology. The aim of this
      review is to revisit the old findings and recent advances of knowledge regarding
      the sub-optimal nutrient conditions on the effect of ethylene biosynthesis and
      perception in plants. The effect of deficiency or excess of the single
      macronutrient or micronutrient on the ethylene pathway and plant responses are
      reviewed and discussed. The synergistic and antagonist effect of the different
      mineral nutrients on ethylene plant responses is critically analyzed. Moreover,
      this review highlights the status of information between nutritional stresses and
      plant response, emphasizing the topics that should be further investigated. 

PMID- 24095920
TI  - Calcium and magnesium elimination enhances accumulation of cardenolides in callus
      cultures of endemic Digitalis species of Turkey.
AB  - Elimination of calcium (Ca), magnesium (Mg) or both from the medium of callus
      cultures of Digitalis davisiana Heywood, Digitalis lamarckii Ivanina, Digitalis
      trojana Ivanina and Digitalis cariensis Boiss. ex Jaub. et Spach increased
      cardenolides production. Callus was induced from hypocotyl segments from one
      month old seedlings were cultured on MS medium containing 0.5 MUg ml(-1)
      thidiazuron (TDZ) and 0.25 MUg ml(-1) indole acetic acid (IAA). After 30 days of
      culture, callus was transferred in hormone-free MS medium (MSO) as well as Ca or
      Mg or both were completely eliminated from same medium. The amount of five
      cardenolides from D. davisiana Heywood, D. lamarckii Ivanina, D. trojana Ivanina
      and D. cariensis Boiss. ex Jaub. et Spach were compared. Higher amounts of five
      cardenolides and total cardenolides were obtained when callus of four Digitalis
      species were incubated on MS medium lacking both Ca and Mg. The mean contents of
      total cardenolides obtained were in the order of D. lamarckii (2017.97 MUg g(
      1))>D. trojana (1385.75 MUg g(-1))>D. cariensis (1038.65 MUg g(-1))>D. davisiana
      (899.86 MUg g(-1)) when both Ca and Mg were eliminated from the medium,
      respectively. This protocol is useful for development of new strategies for the
      large-scale production of cardenolides.

PMID- 24095921
TI  - Manganese-mitigation of cadmium toxicity to seedling growth of Phytolacca acinosa
      Roxb. is controlled by the manganese/cadmium molar ratio under hydroponic
      conditions.
AB  - Manganese (Mn) can interact with cadmium (Cd) in environments and influence the
      toxic effect of Cd on plants. However, few studies have investigated the
      relationship between the Mn/Cd ratio and plant Cd-toxicity along Cd
      concentrations. In this paper, we studied the effects of external Mn/Cd molar
      ratios (0, 10, 30, 50 and 60) on Cd toxicity in the Mn hyperaccumulator and Cd
      tolerant plant, Phytolacca acinosa Roxb., at three Cd levels (50, 100 and 200
      MUM) under hydroponic conditions. Our result showed that seedling growth (y)
      under Cd stress was strongly positively related to the solution Mn/Cd molar ratio
      (SMCR). The relationship between the two variables under solution Cd
      concentrations was well explained by the linear regression model y=a+b1 (SMCR)+b2
      (Solution-Cd). Increasing SMCR significantly reduced the Cd concentration and
      increased the Mn concentration in plant tissues. However, seedling growth was
      consistent with the shoot Mn/Cd molar ratio rather than with the Mn or Cd
      concentrations in plant tissues. At low levels of SMCR (e.g. 0 and 10), elevation
      of Mn distribution in shoot tissues might be a mechanism in P. acinosa seedlings
      to defend against Cd-toxicity. In comparison with low levels of SMCR, high levels
      of SMCR (e.g. 50 and 60) greatly alleviated lipid peroxidation and plant water
      loss, and enhanced photosynthesis. However, the alleviated lipid peroxidation in
      the Mn-mitigation of Cd toxicity was likely to be the secondary effect resulting
      from the antagonism between Mn and Cd in the plant.

PMID- 24095922
TI  - Myoglobin overexpression inhibits reperfusion in the ischemic mouse hindlimb
      through impaired angiogenesis but not arteriogenesis.
AB  - Adaptive vascular remodeling in response to arterial occlusion takes the form of
      capillary growth (angiogenesis) and outward remodeling of pre-existing collateral
      arteries (arteriogenesis). However, the relative contributions of angiogenesis
      and arteriogenesis toward the overall reperfusion response are both highly
      debated and poorly understood. Here, we tested the hypothesis that myoglobin
      overexpressing transgenic mice (MbTg(+)) exhibit impaired angiogenesis in the
      setting of normal arteriogenesis in response to femoral artery ligation, and
      thereby serve as a model for disconnecting these two vascular growth processes.
      After femoral artery ligation, MbTg(+) mice were characterized by delayed distal
      limb reperfusion (by laser Doppler perfusion imaging), decreased foot use, and
      impaired distal limb muscle angiogenesis in both glycolytic and oxidative muscle
      fiber regions at day 7. Substantial arteriogenesis occurred in the primary
      collaterals supplying the ischemic limb in both wild-type and MbTg(+) mice;
      however, there were no significant differences between groups, indicating that
      myoglobin overexpression does not affect arteriogenesis. Together, these results
      uniquely demonstrate that functional collateral arteriogenesis alone is not
      necessarily sufficient for adequate reperfusion after arterial occlusion.
      Angiogenesis is a key component of an effective reperfusion response, and
      clinical strategies that target both angiogenesis and arteriogenesis could yield
      the most efficacious treatments for peripheral arterial disease.

PMID- 24095923
TI  - Nature and mediators of parietal epithelial cell activation in
      glomerulonephritides of human and rat.
AB  - Bowman's capsule parietal epithelial cell activation occurs in several human
      proliferative glomerulonephritides. The cellular composition of the resulting
      hyperplastic lesions is controversial, although a population of CD133(+)CD24(+)
      progenitor cells has been proposed to be a major constituent. Mediator(s)
      involved in proliferation and migration of progenitor cells into the Bowman's
      space have been poorly explored. In a series of 36 renal biopsies of patients
      with proliferative and nonproliferative glomerulopathies, dysregulated
      CD133(+)CD24(+) progenitor cells of the Bowman's capsule invade the glomerular
      tuft exclusively in proliferative disorders. Up-regulation of the CXCR4 chemokine
      receptor on progenitor cells was accompanied by high expression of its ligand,
      SDF-1, in podocytes. Parietal epithelial cell proliferation might be sustained by
      increased expression of the angiotensin II (Ang II) type-1 (AT1) receptor.
      Similar changes of CXCR4, SDF-1, and AT1 receptor expression were found in Munich
      Wistar Fromter rats with proliferative glomerulonephritis. Moreover, an
      angiotensin-converting enzyme inhibitor normalized CXCR4 and AT1 receptor
      expression on progenitors concomitant with regression of crescentic lesions in a
      patient with crescentic glomerulonephritis. These results suggest that glomerular
      hyperplastic lesions derive from the proliferation and migration of renal
      progenitors in response to injured podocytes. The Ang II/AT1 receptor pathway may
      participate, together with SDF-1/CXCR4 axis, to the dysregulated response of
      renal precursors. Thus, targeting the Ang II/AT1 receptor/CXCR4 pathways may be
      beneficial in severe forms of glomerular proliferative disorders.

PMID- 24095924
TI  - ERK5 inhibition ameliorates pulmonary fibrosis via regulating Smad3 acetylation.
AB  - Idiopathic pulmonary fibrosis is a progressive and chronic lung disease of
      unknown cause. Pathologically, the interstitium of the lungs becomes thick and
      stiff, which eventually cause the symptom of breathlessness. It has been
      established that the transforming growth factor-beta1 (TGF-beta1)/Smad signaling
      pathway plays a critical role in the pathogenesis of lung fibrosis. TGF-beta1
      mediated activation of the mitogen-activated protein kinase family affects Smad
      signaling. Extracellular signal-regulated kinase (ERK) 5, an atypical member of
      mitogen-activated protein kinase, promotes cardiac hypertrophy characterized with
      increased expression of fibrotic and extracellular matrix genes. However, the
      role of ERK5 in pulmonary fibrosis remains unknown. Herein, we investigated
      whether ERK5 regulates the pathogenesis of pulmonary fibrosis in both in vitro
      and in vivo systems. Pharmacological inhibition of mitogen activated protein
      kinase kinase 5/ERK5 with BIX02189 and depletion of ERK5 with siRNA-ERK5
      inhibited TGF-beta1-induced extracellular matrix production in lung epithelial
      cells and fibroblasts. Inhibition of ERK5 also blocked the TGF-beta1 signal to
      Smad3 transcriptional activity. However, TGF-beta1-induced Smad3 phosphorylation
      and nuclear translocation were not affected by inhibition of ERK5. Notably, ERK5
      regulates TGF-beta1-induced fibrogenic signaling via Smad3 acetylation.
      Furthermore, ERK5 inhibitor, BIX02189, inhibited lung fibrosis and improved
      survival rate in the bleomycin-induced lung fibrosis model. Our findings indicate
      that ERK5 plays a critical role in TGF-beta1-induced pulmonary fibrosis via
      enhancing Smad3 acetylation. This study may lead to a novel therapeutic strategy
      for treating lung fibrosis.

PMID- 24095925
TI  - Frequent infection of neurons by SV40 virus in SIV-infected macaque monkeys with
      progressive multifocal leukoencephalopathy and meningoencephalitis.
AB  - Simian virus 40 (SV40), family Polyomaviridae, in immunocompromised macaques can
      cause fatal demyelinating central nervous system disease analogous to progressive
      multifocal leukoencephalopathy caused by John Cunningham (JC) virus in
      immunocompromised humans. Recently, we have demonstrated that JC virus can infect
      cerebellar granule cell neurons and cortical pyramidal neurons in
      immunosuppressed people. To examine whether SV40 neuronal infection occurs
      spontaneously in immunosuppressed macaques, we analyzed archival brain specimens
      from 20 simian immunodeficiency virus-infected rhesus with AIDS and 1 cynomolgus
      post-transplant selected with SV40 brain infection from archival records from
      1991 to 2012. In addition to white matter SV40 distribution in classic
      demyelinating progressive multifocal leukoencephalopathy, some of the 21 monkeys
      exhibited meningeal, subpial neocortical, and periventricular virus. This
      distribution pattern corresponded to broader viral tropism with neuronal
      infection in 14 (66.7%) of 21 cases. In all 14 cases, identified neurons were
      positive for early SV40 transcript large T antigen, but only 4 of the 14 cases
      exhibited late viral transcript viral protein 1-positive neurons. SV40-infected
      neurons were detected in frontal, parietal, occipital, and temporal cortices,
      hippocampus, thalamus, and brain stem. These observations confirm that
      spontaneous SV40 neuronal infection occurs in immunosuppressed macaques, which
      parallels JC virus-neuronal infection in immunosuppressed patients. Neuronal
      infection may be an important aspect of both SV40 and JC virus neuropathogenesis
      in their respective hosts.

PMID- 24095926
TI  - Epithelial wounds induce differential phosphorylation changes in response to
      purinergic and EGF receptor activation.
AB  - Protein phosphorylation is a dynamic post-translational modification. Mass
      spectrometry-based quantitation was performed to determine the phosphoproteome
      profile of epithelial cells in response to injury, nucleotide, or epidermal
      growth factor. Phosphotyrosine enrichment used immunoprecipitation and
      immobilized metal affinity chromatography. Nucleotides released after scratch
      wounding activate purinergic receptors, leading to a distinct phosphorylation
      profile on epidermal growth factor receptor (EGFR) compared with its natural
      ligand. ATP induced a 2- to 15-fold phosphorylation increase over control on EGFR
      Y974, Y1086, and Y1148, with minimal phosphorylation intensity on EGFR Y1173
      compared with the level measured in response to epidermal growth factor.
      Differential phosphorylation induced by epidermal growth factor or ATP was site
      specific on Src, Shc, phospholipase Cgamma, protein kinase C, focal adhesion
      kinase, paxillin, and mitogen-activated protein kinases 1, 12, and 13. After
      wounding, the P2Y2 receptor mRNA expression increased, and after knockdown,
      migration and Ca(2+) mobilization were impaired. To examine phosphorylation
      mediated by P2Y2, cells were cultured in media containing stable isotope-labeled
      amino acids, the receptor was knocked down, and the cells were stimulated. Mass
      spectrometry-based comparison of the phosphorylation profiles of control versus
      transfected cells revealed a 50-fold decrease in phosphorylation of EGFR Y974 and
      1086, with no decrease in Y1173 phosphorylation. A similarfold decrease in Src
      Y421 and Y446 and paxillin Y118 was detected, indicating the far-reaching
      importance of the P2Y2 receptor in mediating migration.

PMID- 24095927
TI  - Critical role of FoxO3a in alcohol-induced autophagy and hepatotoxicity.
AB  - Autophagy is a lysosomal degradation process that degrades long-lived cellular
      proteins and damaged organelles as a critical cell survival mechanism in response
      to stress. We recently reported that acute ethanol induces autophagy, which then
      reduces ethanol-induced liver injury. However, the mechanisms by which ethanol
      induces autophagy are not known. In the present study, ethanol treatment
      significantly increased both mRNA and protein levels of various essential
      autophagy-related genes in primary cultured mouse hepatocytes and in mouse liver.
      Both nuclear translocation of FoxO3a and expression of FoxO3a target genes were
      increased in ethanol-treated primary hepatocytes and mouse liver. Overexpression
      of a dominant negative form of FoxO3a inhibited ethanol-induced autophagy-related
      gene expression and enhanced ethanol-induced cell death in primary hepatocytes,
      which suggests that FoxO3a is a key factor in regulating ethanol-induced
      autophagy and cell survival. Resveratrol, a well-known SIRT1 agonist, further
      enhanced ethanol-induced expression of autophagy-related genes, likely via
      increased deacetylation of FoxO3a. Moreover, acute ethanol-treated Foxo3a(-/-)
      mice exhibited decreased autophagy-related gene expression, but enhanced
      steatosis and liver injury, compared with wild-type mice. FoxO3a thus plays a
      critical role in ethanol-induced autophagy in mouse liver. Modulating the FoxO3a
      autophagy pathway may offer novel therapeutic approaches for treating alcoholic
      liver pathogenesis.

PMID- 24095929
TI  - The effect of prenatal exposure to 900-MHz electromagnetic field on the 21-old
      day rat testicle.
AB  - The aim of this study was to investigate the effect of exposure to a 900-MHz
      electromagnetic field (EMF) in the prenatal term on the 21-old-day rat testicle.
      Pregnant rats were divided into control (CG) and EMF (EMFG) groups. EMFG was
      exposed to 900-MHz EMF during days 13-21 of pregnancy. Newborn CG rats were
      obtained from the CG and newborn EMFG (NEMFG) rats from the EMFG. Testicles were
      extracted at postnatal day 21. Lipid peroxidation and DNA oxidation levels,
      apoptotic index and histopathological damage scores were compared. NEMFG rats
      exhibited irregularities in seminiferous tubule basal membrane and epithelium,
      immature germ cells in the lumen, and a decreased diameter in seminiferous
      tubules and thickness of epithelium. Apoptotic index, lipid peroxidation and DNA
      oxidation were higher in NEMFG rats than in NCG. 21-day-old rat testicles exposed
      to 900-MHz EMF in the prenatal term may be adversely affected, and this effect
      persists after birth. 

PMID- 24095928
TI  - Regulation of autophagic flux by dynein-mediated autophagosomes trafficking in
      mouse coronary arterial myocytes.
AB  - Autophagic flux is an important process during autophagy maturation in coronary
      arterial myocytes (CAMs). Here, we defined the role and molecular mechanism of
      the motor protein dynein in the regulation of autophagic flux in CAMs. In mouse
      CAMs, dynein protein is abundantly expressed. Pharmacological or genetic
      inhibition of dynein activity dramatically enhanced 7-ketocholesterol (7-Ket)
      induced expression of the autophagic marker LC3B and increased the cellular
      levels of p62, a selective substrate for autophagy. Inhibition of dynein activity
      increased 7-Ket-induced formation of autophagosomes (APs), but reduced the number
      of autophagolysosomes (APLs) in CAMs. Furthermore, 7-Ket increased the fusion of
      APs with lysosomes and the velocity of APs movement in mouse CAMs, which was
      abolished when the dynein activity in these cells was inhibited. Interestingly, 7
      Ket increased lysosomal Ca(2+) release and stimulated dynein ATPase activity,
      both of which were abolished by NAADP antagonists, NED-19 and PPADS. Taken
      together, our data suggest that NAADP-mediated Ca(2+) release plays a crucial
      role in regulating dynein activity, which mediates APs trafficking and fusion
      with lysosomes to form APLs thus regulating autophagic flux in CAMs under
      atherogenic stimulation. 

PMID- 24095930
TI  - Vitamin D and DBP: the free hormone hypothesis revisited.
AB  - The last five years have witnessed a remarkable renaissance in vitamin D research
      and a complete re-evaluation of its benefits to human health. Two key factors
      have catalyzed these changes. First, it now seems likely that localized, tissue
      specific, conversion of 25-hydroxyvitamin D (25OHD) to 1,25-dihydroxyvitamin D
      (1,25(OH)2D) drives many of the newly recognized effects of vitamin D on human
      health. The second key factor concerns the ongoing discussion as to what
      constitutes adequate or optimal serum vitamin D (25OHD) status, with the
      possibility that vitamin D-deficiency is common to communities across the globe.
      These two concepts appear to be directly linked when low serum concentrations of
      25OHD compromise intracrine generation of 1,25(OH)2D within target tissues. But,
      is this an over-simplification? Pro-hormone 25OHD is a lipophilic molecule that
      is transported in the circulation bound primarily to vitamin D binding protein
      (DBP). While the association between 25OHD and DBP is pivotal for renal handling
      of 25OHD and endocrine synthesis of 1,25(OH)2D, what is the role of DBP for extra
      renal synthesis of 1,25(OH)2D? We hypothesize that binding to DBP impairs
      delivery of 25OHD to the vitamin D-activating enzyme 1alpha-hydroxylase in some
      target cells. Specifically, it is unbound, 'free' 25OHD that drives many of the
      non-classical actions of vitamin D. Levels of 'free' 25OHD are dependent on the
      concentration of DBP and alternative serum binding proteins such as albumin, but
      will also be influenced by variations in DBP binding affinity for specific
      vitamin D metabolites. The aim of this review will be to discuss the merits of
      'free 25OHD' as an alternative marker of vitamin D status, particularly in the
      context of non-classical responses to vitamin D. This article is part of a
      Special Issue entitled '16th Vitamin D Workshop'. 

PMID- 24095932
TI  - Rapid facilitation of ultrasound production and lordosis in female hamsters by
      horizontal cuts between the septum and preoptic area.
AB  - Horizontal cuts between the septum and preoptic area (anterior roof
      deafferentation, or ARD) dramatically affect sexual behavior, and in ways that
      could explain a variety of differences across behavioral categories
      (precopulatory, copulatory), species, and the sexes. Yet little is known about
      how these effects develop. Such information would be useful generally and could
      be pivotal in clarifying the mechanism for ultrasonic vocalization in female
      hamsters. Ultrasounds serve these animals as precopulatory signals that can
      attract males and help initiate mating. Their rates can be increased by either
      ARD or lesions of the ventromedial hypothalamus (VMN). If these effects are
      independent, they would require a mechanism that includes multiple structures and
      pathways within the forebrain and hypothalamus. However, it currently is not
      clear if they are independent: VMN lesions could affect vocalization by causing
      incidental damage to the same fibers targeted by ARD. Fortunately, past studies
      of VMN lesions have described a response with a very distinctive time course.
      This raises the possibility of assessing the independence of the two lesion
      effects by describing just the development of the response to ARD. To accomplish
      this, female hamsters were observed for levels of ultrasound production and
      lordosis before and after control surgery or ARD. As expected, both behaviors
      were facilitated by these cuts. Further, these effects began to appear by two
      days after surgery and were fully developed by six days. These results extend
      previous descriptions of the ARD effect by describing its development and time
      course. In turn, the rapid responses to ARD suggest that these cuts trigger
      disinhibitory changes in pathways that differ from those affected by VMN lesions.

PMID- 24095931
TI  - Early ethanol and water consumption: accumulating experience differentially
      regulates drinking pattern and bout parameters in male alcohol preferring (P) vs.
      Wistar and Sprague Dawley rats.
AB  - Alcohol-preferring (P) rats develop high ethanol intake over several weeks of
      water/10% ethanol (10E) choice drinking. However, it is not yet clear precisely
      what components of drinking behavior undergo modification to achieve higher
      intake. Our concurrent report compared precisely measured daily intake in P vs.
      non-selected Wistar and Sprague Dawley (SD) rats. Here we analyze their drinking
      patterns and bouts to clarify microbehavioral components that are common to rats
      of different genetic backgrounds, vs. features that are unique to each. Under
      sole-fluid conditions P, Wistar and SD rats all consumed water at a high initial
      rate followed by a slow maintenance phase, but 10E - in a distinctly different
      step-like pattern of evenly distributed bouts. During choice period, 10E vs.
      water patterns for P rat appeared as an overlap of sole-fluid patterns. The SD
      rat choice patterns resembled sole-fluid patterns but were less regular. Choice
      patterns in Wistar differed from both P and SD rats, by consisting of intermixed
      small frequent episodes of drinking both 10E and water. Wistar and SD rats
      increased choice ethanol intake by elevating the number of bouts. A key finding
      was that P rat increased choice ethanol intake through a gradual increase of the
      bout size and duration, but kept bout number constant. This supports the
      hypothesis that genetic selection modifies microbehavioral machinery controlling
      drinking bout initiation, duration, and other pattern features. Precision
      analysis of drinking patterns and bouts allows differentiation between genetic
      lines, and provides a venue for study of localized circuit and transmitter
      influences mediating mesolimbic control over ethanol consumption. 

PMID- 24095933
TI  - Early ethanol and water intake: choice mechanism and total fluid regulation
      operate in parallel in male alcohol preferring (P) and both Wistar and Sprague
      Dawley rats.
AB  - The goal of this study was to clarify similar and distinctly different parameters
      of fluid intake during early phases of ethanol and water choice drinking in
      alcohol preferring P-rat vs. non-selected Wistar and Sprague Dawley (SD) rats.
      Precision information on the drinking amounts and timing is needed to analyze
      micro-behavioral components of the acquisition of ethanol intake and to enable a
      search for its causal activity patterns within individual CNS circuits. The
      experiment followed the standard ethanol-drinking test used in P-rat selective
      breeding, with access to water, then 10% ethanol (10E) as sole fluids, and next
      to ethanol/water choice. The novelty of the present approach was to eliminate
      confounding prandial elevations of fluid intake, by time-separating daily food
      from fluid access. P-rat higher initial intakes of water and 10E as sole fluids
      suggest adaptations to ethanol-induced dehydration in P vs. Wistar and SD rats. P
      rat starting and overall ethanol intake during the choice period were the
      highest. The absolute extent of ethanol intake elevation during choice period was
      greatest in Wistar and their final intake levels approached those of P-rat,
      contrary to the hypothesis that selection would produce the strongest elevation
      of ethanol intake. The total daily fluid during ethanol/water choice period was
      strikingly similar between P, Wistar and SD rats. This supports the hypothesis
      for a universal system that gauges the overall intake volume by titrating and
      integrating ethanol and water drinking fluctuations, and indicates a stable daily
      level of total fluid as a main regulated parameter of fluid intake across the
      three lines in choice conditions. The present findings indicate that a stable
      daily level of total fluid comprises an independent physiological limit for daily
      ethanol intake. Ethanol drinking, in turn, stays under the ceiling of this limit,
      driven by a parallel mechanism of ethanol/water choice. 

PMID- 24095934
TI  - Synthesis and investigation of dihydroxychalcones as calpain and cathepsin
      inhibitors.
AB  - In order to identify potential calpain and cathepsin inhibitors we prepared 12
      dihydroxychalcone analogues and tested their ability to inhibit MU-calpain, m
      calpain, cathepsins B and L. In the calpain inhibition test, compound 10
      exhibited the most active inhibitory activity against m-calpain with an IC50
      value of 25.25+/-0.901MUM. With respect to inhibition of cathepsins B and L,
      compound 13 exhibited the most potent inhibitory activity on cathepsin L and
      moderate inhibitory activity on cathepsin B with IC50 values of 2.80+/-0.100 and
      11.47+/-0.087MUM, respectively. Our results suggest the possibility of developing
      dual calpain and cathepsin inhibitors by properly modulating structures and/or
      combining the essential aspects of the functional group effective for specific
      calpain and cathepsin inhibition. 

PMID- 24095935
TI  - Erosive osteoarthritis: a more severe form of radiographic hand osteoarthritis
      rather than a distinct entity?
AB  - OBJECTIVES: To determine whether erosive osteoarthritis shares the same pattern
      of joint involvement and risk profile as increasing grades of non-erosive hand
      osteoarthritis. METHODS: Participants were from two population-based cohorts,
      aged >=50 years, reporting hand symptoms in the previous month. Interphalangeal
      joints were assessed for erosive osteoarthritis (Verbruggen-Veys erosive or
      remodelled phase) and radiographic osteoarthritis (sliding cut-offs of K&L>=2,
      K&L>=3 and K&L=4). At the joint level, similarities in the frequency and pattern
      of erosive and non-erosive osteoarthritis were assessed by Spearman's rank
      correlation coefficients and generalised estimating equations. At the person
      level, individuals with erosive osteoarthritis were compared to those with non
      erosive osteoarthritis using logistic regression, adjusted for age and gender
      (aOR), for the following exposures: family history, previous injury, overuse and
      metabolic factors (BMI, dyslipidaemia, hypertension, diabetes). RESULTS: In 1076
      symptomatic participants the ranked frequency of involvement for erosive joints
      was comparable to joints with K&L>=3 and K&L=4 (r>0.95). Patterns of joint
      involvement in erosive osteoarthritis were strongest for symmetry (aOR=6.5; 95%
      CI 3.0 to 14.1), followed by row (2.0; 0.8 to 5.0) and ray (0.3; 0.0 to 2.5),
      which was similar to joints with K&L>=3 and K&L=4. Individuals with erosive
      osteoarthritis (n=80) had an increased risk of metabolic syndrome (2.7; 1.0 to
      7.1), notably dyslipidaemia (4.7; 2.1 to 10.6) compared with non-erosive
      osteoarthritis classed K&L>=3 (n=193). CONCLUSIONS: The similar frequency of
      radiographic joint involvement and patterning in erosive osteoarthritis and more
      severe non-erosive osteoarthritis is consistent with prevalent erosive
      osteoarthritis being a severe form of hand osteoarthritis rather than a distinct
      entity. Metabolic exposures, dyslipidaemia in particular, may be implicated in
      erosive osteoarthritis.

PMID- 24095936
TI  - The relative risk of aortic aneurysm in patients with giant cell arteritis
      compared with the general population of the UK.
AB  - OBJECTIVES: To evaluate the risk of aortic aneurysm in patients with giant cell
      arteritis (GCA) compared with age-, gender- and location-matched controls.
      METHODS: A UK General Practice Research Database (GPRD) parallel cohort study of
      6999 patients with GCA and 41 994 controls, matched on location, age and gender,
      was carried out. A competing risk model using aortic aneurysm as the primary
      outcome and non-aortic-aneurysm-related death as the competing risk was used to
      determine the relative risk (subhazard ratio) between non-GCA and GCA subjects,
      after adjustment for cardiovascular risk factors. RESULTS: Comparing the GCA
      cohort with the non-GCA cohort, the adjusted subhazard ratio (95% CI) for aortic
      aneurysm was 1.92 (1.52 to 2.41). Significant predictors of aortic aneurysm were
      being an ex-smoker (2.64 (2.03 to 3.43)) or a current smoker (3.37 (2.61 to
      4.37)), previously taking antihypertensive drugs (1.57 (1.23 to 2.01)) and a
      history of diabetes (0.32 (0.19 to 0.56)) or cardiovascular disease (1.98 (1.50
      to 2.63)). In a multivariate model of the GCA cohort, male gender (2.10 (1.38 to
      3.19)), ex-smoker (2.20 (1.22 to 3.98)), current smoker (3.79 (2.20 to 6.53)),
      previous antihypertensive drugs (1.62 (1.00 to 2.61)) and diabetes (0.19 (0.05 to
      0.77)) were significant predictors of aortic aneurysm. CONCLUSIONS: Patients with
      GCA have a twofold increased risk of aortic aneurysm, and this should be
      considered within the range of other risk factors including male gender, age and
      smoking. A separate screening programme is not indicated. The protective effect
      of diabetes in the development of aortic aneurysms in patients with GCA is also
      demonstrated.

PMID- 24095937
TI  - Responsiveness and minimally important difference for the patient-reported
      outcomes measurement information system (PROMIS) 20-item physical functioning
      short form in a prospective observational study of rheumatoid arthritis.
AB  - OBJECTIVE: To estimate responsiveness (sensitivity to change) and minimally
      important difference (MID) for the Patient-Reported Outcomes Measurement
      Information System (PROMIS) 20-item physical functioning scale (PROMIS PF-20).
      METHODS: The PROMIS PF-20, short form 36 (SF-36) physical functioning scale, and
      Health Assessment Questionnaire (HAQ) were administered at baseline, and 6 and 12
      months later to a sample of 451 persons with rheumatoid arthritis. A
      retrospective change (anchor) item was administered at the 12-month follow-up. We
      estimated responsiveness between 12 months and baseline, and between 12 months
      and 6 months using one-way analysis of variance F-statistics. We estimated the
      MID for the PROMIS PF-20 using prospective change for people reporting getting 'a
      little better' or 'a little worse' on the anchor item. RESULTS: F-statistics for
      prospective change on the PROMIS PF-20, SF-36 and HAQ by the anchor item over 12
      and 6 months (in parentheses) were 16.64 (14.98), 12.20 (7.92) and 10.36 (12.90),
      respectively. The MID for the PROMIS PF-20 was 2 points (about 0.20 of an SD).
      CONCLUSIONS: The PROMIS PF-20 is more responsive than two widely used ('legacy')
      measures. The MID is a small effect size. The measure can be useful for assessing
      physical functioning in clinical trials and observational studies.

PMID- 24095938
TI  - Identification of small molecule inhibitors of RANKL and TNF signalling as anti
      inflammatory and antiresorptive agents in mice.
AB  - INTRODUCTION: Inflammatory joint diseases such as rheumatoid arthritis are
      associated with local bone erosions and systemic bone loss, mediated by increased
      osteoclastic activity. The receptor activator of nuclear factor (NF) kappaB
      ligand (RANKL) plays a key role in mediating inflammation-induced bone loss,
      whereas tumour necrosis factor (TNF) plays a central role in the inflammatory
      process. Here we tested whether a recently identified class of small molecule
      inhibitors of RANKL signalling (ABD compounds) also affect TNF signalling and
      whether these compounds inhibit inflammation in an animal model of rheumatoid
      arthritis. METHODS: The inhibitory effects of the ABD compounds on TNF-induced
      signalling were tested in mouse macrophage cultures by western blotting and in an
      NFkappaB luciferase-reporter cell line. The anti-inflammatory effects of the
      compounds were tested in the mouse collagen-induced arthritis model of rheumatoid
      arthritis. RESULTS: The ABD compounds ABD328 and ABD345 both inhibited TNF
      induced activation of the NFkappaB pathway and the extracellular signal-regulated
      kinase (ERK) and Jun kinase (JNK) mitogen activated protein kinases (MAPKs). When
      tested in the mouse collagen-induced arthritis model of rheumatoid arthritis, the
      compounds suppressed inflammatory arthritis, inhibited joint destruction and
      prevented systemic bone loss. Furthermore, one of the compounds (ABD328) showed
      oral activity. CONCLUSIONS: Here we describe a novel class of small molecule
      compounds that inhibit both RANKL- and TNF-induced NFkappaB and MAPK signalling
      in osteoclasts and macrophages, and inflammation and bone destruction in a mouse
      model of rheumatoid arthritis. These novel compounds therefore represent a
      promising new class of treatments for inflammatory diseases, such as rheumatoid
      arthritis.

PMID- 24095939
TI  - Role of vascular channels as a novel mechanism for subchondral bone damage at
      cruciate ligament entheses in osteoarthritis and inflammatory arthritis.
AB  - OBJECTIVES: The purpose of this work was to test whether normal peri-entheseal
      vascular anatomy at anterior and posterior cruciate ligaments (ACL and PCL) was
      associated with distribution of peri-entheseal bone erosion/bone marrow lesions
      (BMLs) in inflammatory arthritis (IA) and osteoarthritis (OA). METHODS: Normal
      microanatomy was defined histologically in mice and by 3 T MRI and histology in
      21 cadaveric knees. MRI of 89 patients from the Osteoarthritis Initiative and 27
      patients with IA was evaluated for BMLs at ACL and PCL entheses. Antigen-induced
      arthritis (AIA) in mice was evaluated to ascertain whether putative peri
      entheseal vascular regions influenced osteitis and bone erosion. RESULTS:
      Vascular channels penetrating cortical bone were identified in knees of non
      arthritic mice adjacent to the cruciate ligaments. On MRI of normal cadavers,
      vascular channels adjacent to the ACL (64% of cases) and PCL (71%) entheses were
      observed. Histology of 10 macroscopically normal cadaveric specimens confirmed
      the location of vascular channels and associated subclinical changes including
      subchondral bone damage (80% of cases) and micro-cyst formation (50%). In the AIA
      model, vascular channels clearly provided a site for inflammatory tissue entry
      and osteoclast activation. MRI showed BMLs in the same topographic locations in
      both patients with early OA (41% ACL, 59% PCL) and IA (44%, 33%). CONCLUSION: The
      findings show that normal ACL and PCL entheses have immediately adjacent vascular
      channels which are common sites of subtle bone marrow pathology in non-arthritic
      joints. These channels appear to be key determinants in bone damage in
      inflammatory and degenerative arthritis.

PMID- 24095941
TI  - Zinc causes acute impairment of glutathione metabolism followed by coordinated
      antioxidant defenses amplification in gills of brown mussels Perna perna.
AB  - Zinc demonstrates protective and antioxidant properties at physiological levels,
      although these characteristics are not attributed at moderate or high
      concentrations. Zinc toxicity has been related to a number of factors, including
      interference with antioxidant defenses. In particular, the inhibition of
      glutathione reductase (GR) has been suggested as a possible mechanism for acute
      zinc toxicity in bivalves. The present work investigates the biochemical effects
      of a non-lethal zinc concentration on antioxidant-related parameters in gills of
      brown mussels Perna perna exposed for 21 days to 2.6 MUM zinc chloride. After 2
      days of exposure, zinc caused impairment of the antioxidant system, decreasing GR
      activity and glutathione levels. An increase in antioxidant defenses became
      evident at 7 and 21 days of exposure, as an increase in superoxide dismutase and
      glutathione peroxidase activity along with restoration of glutathione levels and
      GR activity. After 7 and 21 days, an increase in cellular peroxides and lipid
      peroxidation end products were also detected, which are indicative of oxidative
      damage. Changes in GR activity contrasts with protein immunoblotting data,
      suggesting that zinc produces a long lasting inhibition of GR. Contrary to the
      general trend in antioxidants, levels of peroxiredoxin 6 decreased after 21 days
      of exposure. The data presented here support the hypothesis that zinc can impair
      thiol homeostasis, causes an increase in lipid peroxidation and inhibits GR,
      imposing a pro-oxidant status, which seems to trigger homeostatic mechanisms
      leading to a subsequent increase on antioxidant-related defenses.

PMID- 24095940
TI  - Prevalence of comorbidities in rheumatoid arthritis and evaluation of their
      monitoring: results of an international, cross-sectional study (COMORA).
AB  - BACKGROUND: PATIENTS with rheumatoid arthritis (RA) are at increased risk of
      developing comorbid conditions. OBJECTIVES: To evaluate the prevalence of
      comorbidities and compare their management in RA patients from different
      countries worldwide. METHODS:  STUDY DESIGN: international, cross-sectional.
      PATIENTS: consecutive RA patients. DATA COLLECTED: demographics, disease
      characteristics (activity, severity, treatment), comorbidities (cardiovascular,
      infections, cancer, gastrointestinal, pulmonary, osteoporosis and psychiatric
      disorders). RESULTS: Of 4586 patients recruited in 17 participating countries,
      3920 were analysed (age, 56+/-13 years; disease duration, 10+/-9 years (mean+/
      SD); female gender, 82%; DAS28 (Disease Activity Score using 28 joints)
      erythrocyte sedimentation rate, 3.7+/-1.6 (mean+/-SD); Health Assessment
      Questionnaire, 1.0+/-0.7 (mean+/-SD); past or current methotrexate use, 89%; past
      or current use of biological agents, 39%. The most frequently associated diseases
      (past or current) were: depression, 15%; asthma, 6.6%; cardiovascular events
      (myocardial infarction, stroke), 6%; solid malignancies (excluding basal cell
      carcinoma), 4.5%; chronic obstructive pulmonary disease, 3.5%. High intercountry
      variability was observed for both the prevalence of comorbidities and the
      proportion of subjects complying with recommendations for preventing and managing
      comorbidities. The systematic evaluation of comorbidities in this study detected
      abnormalities in vital signs, such as elevated blood pressure in 11.2%, and
      identified conditions that manifest as laboratory test abnormalities, such as
      hyperglycaemia in 3.3% and hyperlipidaemia in 8.3%. CONCLUSIONS: Among RA
      patients, there is a high prevalence of comorbidities and their risk factors. In
      this multinational sample, variability among countries was wide, not only in
      prevalence but also in compliance with recommendations for preventing and
      managing these comorbidities. Systematic measurement of vital signs and
      laboratory testing detects otherwise unrecognised comorbid conditions.

PMID- 24095942
TI  - Bromodimethylsulfonium bromide/silver triflate-promoted glycosylations using
      glycosyl allenoates as donors.
AB  - A series of novel glycosyl allenoates were prepared by condensions of hemiacetals
      with 3,3-dimethyl-4,5-allenoic acid. Their glycosylations with various alcohols
      under the promotion of bromodimethylsulfonium bromide/silver triflate smoothly
      proceeded to produce disaccharides. Studies reveal that allenic group is crucial
      for the efficient glylcosylation of glycosyl allenoate. 

PMID- 24095943
TI  - Applications of organoboron compounds in carbohydrate chemistry and glycobiology:
      analysis, separation, protection, and activation.
AB  - The reversible covalent interactions between organoboron compounds and diols have
      been applied for many years in carbohydrate chemistry. They form the basis of
      efficient methods for the detection of carbohydrates, and applications in
      cellular imaging and glycoprotein analysis are beginning to emerge. The
      interactions are also of widespread utility in carbohydrate synthesis: depending
      upon the coordination geometry at boron, either protection or activation of a
      bound diol motif may be achieved. This review article uses recent examples to
      illustrate the breadth of applications of organoboron compounds in carbohydrate
      chemistry. 

PMID- 24095944
TI  - alpha-Bromophosphonate analogs of glucose-6-phosphate are inhibitors of glucose-6
      phosphatase.
AB  - Glucose-6-phosphatase (G6Pase) is an essential metabolic enzyme that has
      upregulated activity in Type II diabetes. Synthetic analogs of the G6Pase
      substrate, glucose-6-phosphate (G6P), may provide new tools to probe enzyme
      activity, or lead to specific inhibitors of glycosylphosphatase enzymes. Here we
      have developed synthetic routes to a panel of non-hydrolyzable G6P analogs
      containing alpha-bromo, alpha,alpha-dibromo, and alpha-bromo-alpha,beta
      unsaturated phosphonates compatible with a carbohydrate nucleus. We confirm that
      these functionalities have potency as inhibitors of G6Pase in vitro, providing a
      series of new phosphate isosteres that can be exploited for inhibitor design. 

PMID- 24095947
TI  - Variable alteration of regional tissue oxygen pressure in rat hippocampus by
      acute swimming exercise.
AB  - One of the events in the brain is an increasing cerebral blood flow during
      exercise. The tissue oxygen level may be increased because blood flow correlates
      with tissue oxygen level. However, it is little known whether the tissue oxygen
      pressure in hippocampal region (Hip-pO2) will be affected by exercise. AIMS: The
      aim of this study is to examine Hip-pO2 levels in the hippocampus and its changes
      during exercise. MAIN METHODS: We applied improved Clark-type electrodes to
      measure Hip-pO2 level in the hippocampus of rats that were subjected to three
      groups, 2h swimming without weights (low intensity, n=6), 2h swimming with a 5 g
      weight (moderate intensity, n=6), and 2h swimming with a 10 g weight (high
      intensity, n=6). KEY FINDINGS: Exercise affected the Hip-pO2 level, the responses
      varied with the exercise intensity and duration. Interestingly during and after
      the Low intensity swimming the Hip-pO2 level showed long lasting enhancement (10
      20% above resting level). But the moderate and high intensity swimming increased
      Hip-pO2 level at the start of the swimming (50%, P<0.05 and slightly above
      resting level, respectively, at 10 min of 2h swimming) and then began to decrease
      (at 120 min and 10 min of 2h swimming, respectively), and suppressed the Hip-pO2
      levels during post exercise resting period (2h) (85-95% of resting level, NS and
      60-70% of resting level P<0.05, respectively). SIGNIFICANCE: We propose that
      exercise-induced hippocampal hyper/hypo oxygen condition may participate in
      beneficial exercise effects on brain function.

PMID- 24095946
TI  - Fatty acid-induced angiogenesis in first trimester placental trophoblast cells:
      possible roles of cellular fatty acid-binding proteins.
AB  - Angiogenesis is involved in the growth of new blood vessels from the existing
      one. Consequently, angiogenesis plays an indispensable role in tissue growth and
      repair including early placentation processes. Besides angiogenic growth factors
      (vascular endothelial growth factor (VEGF), angiopoietin-like 4 (ANGPTL4),
      placental growth factor (PlGF), platelet derived growth factor (PDGF), fibroblast
      growth factors (FGF)), dietary fatty acids (c>16) also directly or indirectly
      modulate angiogenic processes in tumors and other cell systems. Usually n-3 fatty
      acids inhibit whereas n-6 fatty acids stimulate angiogenesis in tumors and other
      cells. Contrary to this, docosahexaenoic acid, 22:6n-3 (DHA) and other fatty
      acids including conjugated linoleic acid stimulate angiogenesis in placental
      first trimester cells. In addition to the stimulation of expression of major
      angiogenic factors such as VEGF and ANGPTL4, fatty acids also stimulate
      expression of intracellular fatty acid-binding proteins (FABPs) FABP-4 and FABP-3
      those are known to directly modulate angiogenesis. Emerging data indicate that
      FABPs may be involved in the angiogenesis process. This paper reviews the fatty
      acid mediated angiogenesis process and the involvement of their binding proteins
      in these processes. 

PMID- 24095945
TI  - Myosin light chain 2-based selection of human iPSC-derived early ventricular
      cardiac myocytes.
AB  - Applications of human induced pluripotent stem cell derived-cardiac myocytes
      (hiPSC-CMs) would be strengthened by the ability to generate specific cardiac
      myocyte (CM) lineages. However, purification of lineage-specific hiPSC-CMs is
      limited by the lack of cell marking techniques. Here, we have developed an iPSC
      CM marking system using recombinant adenoviral reporter constructs with atrial-
      or ventricular-specific myosin light chain-2 (MLC-2) promoters. MLC-2a and MLC-2v
      selected hiPSC-CMs were purified by fluorescence-activated cell sorting and their
      biochemical and electrophysiological phenotypes analyzed. We demonstrate that the
      phenotype of both populations remained stable in culture and they expressed the
      expected sarcomeric proteins, gap junction proteins and chamber-specific
      transcription factors. Compared to MLC-2a cells, MLC-2v selected CMs had larger
      action potential amplitudes and durations. In addition, by immunofluorescence, we
      showed that MLC-2 isoform expression can be used to enrich hiPSC-CM consistent
      with early atrial and ventricular myocyte lineages. However, only the ventricular
      myosin light chain-2 promoter was able to purify a highly homogeneous population
      of iPSC-CMs. Using this approach, it is now possible to develop ventricular
      specific disease models using iPSC-CMs while atrial-specific iPSC-CM cultures may
      require additional chamber-specific markers. 

PMID- 24095948
TI  - Saccharin enhances neurite extension by regulating organization of the
      microtubules.
AB  - AIMS: In the present study, we found that saccharin, an artificial calorie-free
      sweetener, promotes neurite extension in the cultured neuronal cells. The
      purposes of this study are to characterize the effect of saccharine on neurite
      extension and to determine how saccharin enhances neurite extension. MAIN
      METHODS: The analyses were performed using mouse neuroblastoma N1E-115 cells and
      rat pheochromocytoma PC12 cells. Neurite extension was evaluated by counting the
      cells bearing neurites and measuring the length of neurites. Formation, severing
      and transportation of the microtubules were evaluated by immunostaining and
      western blotting analysis. KEY FINDINGS: Deprivation of glucose increased the
      number of N1E-115 cells bearing long processes. And the effect was inhibited by
      addition of glucose. Saccharin increased the number of these cells bearing long
      processes in a dose-dependent manner and total neurite length and longest neurite
      length in each cell. Saccharin also had a similar effect on NGF-treated PC12
      cells. Saccharin increased the amount of the microtubules reconstructed after
      treatment with nocodazole, a disruptor of microtubules. The effect of saccharin
      on microtubule reconstruction was not influenced by dihydrocytochalasin B, an
      inhibitor of actin polymerization, indicating that saccharin enhances microtubule
      formation without requiring actin dynamics. In the cells treated with
      vinblastine, an inhibitor of microtubule polymerization, after microtubule
      reorganization, filamentous microtubules were observed more distantly from the
      centrosome in saccharin-treated cells, indicating that saccharin enhances
      microtubule severing and/or transportation. SIGNIFICANCE: These results suggest
      that saccharin enhances neurite extension by promoting microtubule organization.

PMID- 24095949
TI  - Work stress: its components and its association with self-reported health
      outcomes in a garment factory in Bangladesh-Findings from a cross-sectional
      study.
AB  - Bangladesh is one of the leading exporters of ready-made garments (RMG) worldwide
      producing at very low cost almost exclusively for Western markets. Empirical
      evidence on psychologically adverse working conditions and their association with
      health in the RMG setting remains sparse. Drawing on insights from previous
      ethnographic research, we conducted a cross-sectional epidemiological study among
      332 RMG workers in Dhaka, Bangladesh. High work-related demands and poor
      interpersonal resources represented key components of work stress and were
      important determinants of poor health. The key work stress components observed in
      this study partly differed from those identified in Western work place settings. 

PMID- 24095950
TI  - An improved method for the derivation of high quality iPSCs in the absence of c
      Myc.
AB  - Induced pluripotent stem cells (iPSCs) hold tremendous potential for the
      development of new regenerative medicine therapies and the study of molecular
      mechanisms of pluripotency and development. However, reactivation of c-Myc, which
      results in tumor formation in chimeric mice, is a major roadblock in the
      translation of iPSCs into therapies. Although ectopic expression of c-Myc is not
      absolutely required for somatic reprogramming, in the absence of c-Myc, the
      overall efficiency of reprogramming is drastically reduced and the reprogramming
      time is increased. Subtle, abnormal epigenetic modifications in iPSCs derived in
      the absence of c-Myc have also been documented. Therefore, we developed a
      reprogramming method without c-Myc to generate high-quality iPSCs, a prerequisite
      to harnessing the full potential of iPSCs. In this study, we determined that
      serum replacement (SR)-based culture conditions dramatically increased the
      transcription factor-mediated reprogramming of mouse embryonic fibroblast cells
      (MEFs). The process was shortened to approximately 8 days when Oct4/Sox2/Klf4
      (3F)-transduced MEFs were first cultured for 3 days under low serum conditions
      (LS protocol). The 3F-derived iPSCs that were generated by this method resembled
      mouse ES cells (mESCs) in morphology, gene expression, and in vitro
      differentiation. Finally, we observed that 3F-derived iPSC colonies were able to
      reach definite pluripotency in terms of molecular signatures when the catalytic
      function of c-Myc was tolerated. The 3F induction of pluripotency described here
      should facilitate the use of iPSCs and may also facilitate the mechanistic
      dissection of somatic reprogramming. 

PMID- 24095951
TI  - Assessing the internal and external validity of mobile health physical activity
      promotion interventions: a systematic literature review using the RE-AIM
      framework.
AB  - BACKGROUND: Mobile health (mHealth) interventions are effective in promoting
      physical activity (PA); however, the degree to which external validity indicators
      are reported is unclear. OBJECTIVE: The purpose of this systematic review was to
      use the RE-AIM (reach, effectiveness, adoption, implementation, and maintenance)
      framework to determine the extent to which mHealth intervention research for
      promoting PA reports on factors that inform generalizability across settings and
      populations and to provide recommendations for investigators planning to conduct
      this type of research. METHODS: Twenty articles reflecting 15 trials published
      between 2000 and 2012 were identified through a systematic review process (ie,
      queries of three online databases and reference lists of eligible articles) and
      met inclusion criteria (ie, implementation of mobile technologies, target
      physical activity, and provide original data). Two researchers coded each article
      using a validated RE-AIM data extraction tool (reach, efficacy/effectiveness,
      adoption, implementation, maintenance). Two members of the study team
      independently abstracted information from each article (inter-rater reliability
      >90%) and group meetings were used to gain consensus on discrepancies. RESULTS:
      The majority of studies were randomized controlled trials (n=14). The average
      reporting across RE-AIM indicators varied by dimension (reach=53.3%, 2.67/5;
      effectiveness/efficacy=60.0%, 2.4/4; adoption=11.1%, 0.7/6; implementation=24.4%,
      0.7/3; maintenance=0%, 0/3). While most studies described changes in the primary
      outcome (effectiveness), few addressed the representativeness of participants
      (reach) or settings (adoption) and few reported on issues related to maintenance
      and degree of implementation fidelity. CONCLUSIONS: This review suggests that
      more focus is needed on research designs that highlight and report on both
      internal and external validity indicators. Specific recommendations are provided
      to encourage future mHealth interventionists and investigators to report on
      representativeness, settings, delivery agents for planned interventions, the
      extent to which protocol is delivered as intended, and maintenance of effects at
      the individual or organizational level.

PMID- 24095952
TI  - Increased expression of heat shock protein 70 in chronic obstructive pulmonary
      disease.
AB  - BACKGROUND: Heat shock protein 70 (HSP70) plays a critical role in the process of
      inflammation and innate immunity response under environmental stress. OBJECTIVES:
      This study was to investigate HSP70 expression in the peripheral lung tissues of
      chronic obstructive pulmonary disease (COPD) patients and in human bronchial
      epithelial cells (16-HBE) exposed to cigarette smoke extract (CSE). METHODS:
      Peripheral lung tissues were collected after lung cancer resection from 26
      patients without COPD, 20 with mild COPD and 15 with advanced COPD, classified by
      lung function criteria. Among these cases, 37 were smokers and 24 non-smokers.
      Lung tissues were examined for histopathological changes and levels of HSP70 and
      IL-8. Cultured 16-HBE cells were stimulated with CSE in the absence or presence
      of HSP70 neutralizing antibody and the expressions of IL-8 and phospho-EGFR
      protein were determined. RESULTS: Compared to patients without COPD, the levels
      of HSP70 and IL-8 were significantly increased in the lung tissues of COPD
      patients and positively correlated with the severity of the disease. The HSP70
      expression was significantly higher in current smokers than that in non-smokers.
      Moreover, CSE-induced HSP70 significantly enhanced IL-8 production and EGFR
      phosphorylation in 16-HBE cells. The increases in IL-8 and phospho-EGFR were
      blocked by anti-HSP70 antibody. CONCLUSIONS: Our study clarified that increased
      expression of HSP70 is closely related to COPD disease severity and smoking
      status. Extracellular HSP70 regulated chemokine productions and EGFR
      phosphorylation and plays an important role in the CSE-induced inflammatory and
      innate immunity responses in bronchial epithelia cells.

PMID- 24095953
TI  - Maturation inside and outside bone marrow dendritic cells (BMDCs) modulated by
      interferon-alpha (IFN-alpha).
AB  - Interferons are made by cells in response to appropriate stimuli such as viruses,
      bacteria, parasites or tumor cells and are released into the surrounding medium.
      They then bind to receptors on target cells to allow for communication between
      cells to trigger the protective defenses of the immune system that eradicate
      pathogens or tumors. IFN-alpha is produced by leukocytes and is mainly involved
      in innate immune response against viral or bacterial infections and for tumor
      control. The aim of this work is to explore the detailed modulation of IFN-alpha
      on phenotypic and functional maturation inside and outside murine bone marrow
      derived dendritic cells (BMDCs). The maturity of BMDCs post treatment with IFN
      alpha was evaluated with conventional light microscope and transmission electron
      microscopy (TEM) for morphology changes; flow cytometry (FCM) for changes of
      surface molecules on BMDCs; cytochemistry, acid phosphatase activity (ACP) test,
      and FITC-dextran bio-assay for biochemistry analysis and enzyme-linked
      immunosorbent assay (ELISA) for cytokine production by BMDCs. We have shown that
      IFN-alpha 1) up-regulates the expression of MHC II, CD40, CD83, CD80 and CD86
      molecules on BMDCs; 2) down-regulates the rates of pinocytosis and phagocytosis
      by BMDCs as evidenced by the results of decreased ACP, and FITC-dextran bio
      assay; 3) enhances the ability of BMDCs to drive T cell function; and 4) induces
      higher levels of IL-12 and TNF-alpha secreted by BMDCs. Therefore, we conclude
      that IFN-alpha can efficiently promote the maturation of BMDCs through detailed
      modulation inside and outside BMDCs. Our study has provided more detailed data on
      changes of BMDCs modulated by IFN-alpha, and rationale on future application of
      IFN-alpha for enhancing host immunity and potent adjuvant administration in the
      design of DC-based vaccines.

PMID- 24095955
TI  - Fourier transform infrared for noninvasive optical diagnosis of oral,
      oropharyngeal, and laryngeal cancer.
AB  - The 5-year survival rate for advanced head and neck cancers is 50%. There is
      currently no noninvasive method or effective screening procedure available to
      diagnose head and neck cancer at the earliest stages when it is still highly
      curable. This study aims to show how Fourier transform infrared (FTIR)
      spectroscopy could be used as a sensitive, noninvasive, low cost technique to
      diagnose head and neck cancer at an earlier stage and, thus, increase the
      likelihood of survival. Sputum samples were collected from 16 cases with oral or
      oropharyngeal cancer, 8 cases with laryngeal cancer patients and 15 normal
      controls. Cell pellets were produced from each of these samples and used to
      generate FTIR spectra within the 'biochemical fingerprint' wavenumber region of
      1800 to 950 cm(-1). Discrimination between cancer and normal sputum was achieved
      using infrared wavenumbers 1650 cm(-1), 1550 cm(-1), and 1042 cm(-1) determined
      by robust feature selection. These 3 wavenumbers were used to develop potential
      models to discriminate both oropharyngeal and laryngeal cancer from normal
      control. In cancer cases, the absorbance levels for 1550 cm(-1) were increased
      relative to controls, whereas 1042 cm(-1) absorbance was decreased suggesting
      changes to protein and glycoprotein structure within sputa cells. This
      preliminary study shows potential for how FTIR could be developed into a
      simplistic diagnostic tool that could easily be implemented by a nonspecialist to
      diagnose and monitor head and neck cancer. The method could especially provide a
      means for detecting laryngeal cancer hidden from noninvasive observation. 

PMID- 24095954
TI  - Zebrafish models of dyslipidemia: relevance to atherosclerosis and angiogenesis.
AB  - Lipid and lipoprotein metabolism in zebrafish and in humans are remarkably
      similar. Zebrafish express all major nuclear receptors, lipid transporters,
      apolipoproteins and enzymes involved in lipoprotein metabolism. Unlike mice,
      zebrafish express cetp and the Cetp activity is detected in zebrafish plasma.
      Feeding zebrafish a high cholesterol diet, without any genetic intervention,
      results in significant hypercholesterolemia and robust lipoprotein oxidation,
      making zebrafish an attractive animal model to study mechanisms relevant to early
      development of human atherosclerosis. These studies are facilitated by the
      optical transparency of zebrafish larvae and the availability of transgenic
      zebrafish expressing fluorescent proteins in endothelial cells and macrophages.
      Thus, vascular processes can be monitored in live animals. In this review
      article, we discuss recent advances in using dyslipidemic zebrafish in
      atherosclerosis-related studies. We also summarize recent work connecting lipid
      metabolism with regulation of angiogenesis, the work that considerably benefited
      from using the zebrafish model. These studies uncovered the role of aibp, abca1,
      abcg1, mtp, apoB, and apoC2 in regulation of angiogenesis in zebrafish and paved
      the way for future studies in mammals, which may suggest new therapeutic
      approaches to modulation of excessive or diminished angiogenesis contributing to
      the pathogenesis of human disease. 

PMID- 24095956
TI  - Impact assessment of agricultural inputs into a Mediterranean coastal lagoon (Mar
      Menor, SE Spain) on transplanted clams (Ruditapes decussatus) by biochemical and
      physiological responses.
AB  - The Mar Menor is a coastal lagoon threatened by the development of intensive
      agriculture in the surrounding areas. Large amounts of pesticides from these
      areas are discharged into El Albujon, a permanent watercourse flowing into the
      lagoon. We have used a multi-biomarker approach to assess the biological effects
      of agricultural pollution on a bivalve species. Biomarkers indicative of
      neurotoxicity (acetylcholinesterase, AChE), oxidative stress (catalase, CAT;
      glutathione reductase, GR and lipid peroxidation, LPO), phase II
      biotransformation of xenobiotics (glutathione S-transferase, GST) and
      physiological stress (scope for growth, SFG) were measured in clams transplanted
      to four sites of the lagoon (two reference sites and two sites affected by the
      dispersion of the effluent of the El Albujon), for exposure periods of 7 and 22
      days. The hazards of this effluent were also examined by simultaneously measuring
      up to 83 contaminants (pesticides, PCBs, PAHs and others) in samples of fresh
      water from the watercourse mouth and seawater from the deployed sites, as well as
      the bioaccumulation of organochlorinated compounds and PAHs in the transplanted
      animals. Biomarker responses showed marked differences between reference and
      affected sites after 7 and 22 days. However it was only after 22 days that
      principal component analysis (PCA) of the biomarker responses distinguished
      between clams deployed in sites affected by the dispersion of the effluent of the
      watercourse and those from the reference sites. The chemical analysis of water
      showed high concentrations of pesticides close to El Albujon watercourse mouth,
      with the greatest input flux corresponding to the organophosphate chlorpyrifos,
      followed by pendimethalin and naphthalene, and at lower levels acenaphthene,
      terbuthylazine-desethyl and chlorpyrifos-methyl. In this regard, PCA analysis
      showed that the biological effects of the mixture of pesticides in caged clams
      after 22 days were reduced levels of AchE and SFG and increased levels of GR and
      phase II GST activity. An integrated biomarker response index was calculated from
      the combination of these biomarkers, proving useful for the assessment of the
      impact of agricultural pollution in caged clams. 

PMID- 24095957
TI  - Differential effect of waterborne cadmium exposure on lipid metabolism in liver
      and muscle of yellow catfish Pelteobagrus fulvidraco.
AB  - The present study was conducted to investigate the effect of waterborne cadmium
      (Cd) exposure on lipid metabolism in liver and muscle of juvenile yellow catfish
      Pelteobagrus fulvidraco. Yellow catfish were exposed to 0 (control), 0.49 and
      0.95 mg Cd/l, respectively, for 6 weeks, the lipid deposition, Cd accumulation,
      the activities and expression level of several enzymes as well as the mRNA
      expression of transcription factors involved in lipid metabolism in liver and
      muscle were determined. Waterborne Cd exposure reduced growth performance, but
      increased Cd accumulation in liver and muscle. In liver, lipid content, the
      activities and the mRNA expression of lipogenic enzymes (6-phosphogluconate
      dehydrogenase (6PGD), glucose-6-phosphate dehydrogenase (G6PD), fatty acid
      synthetase (FAS)) and lipoprotein lipase (LPL) activity increased with increasing
      waterborne Cd concentrations. However, the mRNA expressions of LPL and peroxisome
      proliferators-activated receptor (PPAR) alpha were down-regulated by Cd exposure.
      Carnitine palmitoyltransferase 1 (CPT1) activity as well as the mRNA expressions
      of CPT1 and PPARgamma showed no significant differences among the treatments. In
      muscle, lipid contents showed no significant differences among the treatments.
      The mRNA expression of 6PGD, FAS, CPT1, LPL, PPARalpha and PPARgamma were down
      regulated by Cd exposure. Thus, our study indicated that Cd triggered hepatic
      lipid accumulation through the improvement of lipogenesis, and that lipid
      homeostasis in muscle was probably conducted by the down-regulation of both
      lipogenesis and lipolysis. Different variation patterns of lipid metabolism to
      waterborne Cd exposure indicated the tissue-specific regulatory effect of lipid
      metabolism under waterborne Cd exposure. To our knowledge, the present study
      provides, for the first time, evidence that waterborne chronic Cd exposure can
      disturb the normal processes of lipid metabolism at both the enzymatic and
      molecular levels, and in two tissues (the liver and muscle).

PMID- 24095959
TI  - Focus on gastrointestinal and liver cancers.
AB  - Digestive cancers, such as colorectal cancer, gastric cancer and liver cancer,
      remain major threats to human health in coming decades and their epidemiology is
      under dynamic changes. Recent advances in genotyping and sequencing technologies
      together with other molecular and cellular biology techniques have led to a
      clearer delineation of the pathogenic mechanisms underlying genetic and
      environmental factors that contribute to digestive cancers. Such expansion of
      knowledge continues to fuel the development of novel biomarkers and therapeutics.
      In this special issue of Seminars in Cancer Biology, hot topics in basic and
      translational research of digestive cancers will be reviewed. 

PMID- 24095958
TI  - Mild oxidative stress induces S-glutathionylation of STAT3 and enhances
      chemosensitivity of tumoural cells to chemotherapeutic drugs.
AB  - STAT3 is a transcription factor constitutively activated in a variety of cancers
      that has a critical role in the inhibition of apoptosis and induction of
      chemoresistance. Inhibition of the STAT3 signaling pathway suppresses cell
      survival signals and leads to apoptosis in cancer cells, suggesting that direct
      inhibition of STAT3 function is a viable therapeutic approach. Herein, we
      identify the naturally occurring sesquiterpene lactone cynaropicrin as a potent
      inhibitor of both IL-6-inducible and constitutive STAT3 activation (IC50=12 MUM).
      Cynaropicrin, which contains an alpha-beta-unsaturated carbonyl moiety and acts
      as potent Michael reaction acceptor, induces a rapid drop in intracellular
      glutathione (GSH) concentration, thereby triggering S-glutathionylation of STAT3.
      Furthermore, glutathione ethylene ester, the cell permeable form of GSH, reverts
      the inhibitory action of cynaropicrin on STAT3 tyrosine phosphorylation. These
      findings suggest that this sesquiterpene lactone is able to induce redox
      dependent post-translational modification of cysteine residues of STAT3 protein
      to regulate its function. STAT3 inhibition led to the suppression of two anti
      apoptotic genes, Bcl-2 and survivin, in DU145 cells that constitutively express
      active STAT3. This event may be responsible for the decline in cell viability
      after cynaropicrin treatment. As revealed by PI/annexin-V staining, PARP
      cleavage, and DNA ladder formation, cynaropicrin cytotoxicity is mediated by
      apoptosis. Finally, cynaropicrin displayed a slight to strong synergism with two
      well-established chemotherapeutic drugs, cisplatin and docetaxel. Taken together
      our studies suggest that cynaropicrin suppresses the STAT3 pathway, leading to
      the down-regulation of STAT3-dependent gene expression and chemosensitization of
      tumour cells to chemotherapy.

PMID- 24095960
TI  - Apolar Laurus nobilis leaf extracts induce cytotoxicity and apoptosis towards
      three nervous system cell lines.
AB  - In the course of a bioactivity screening of Mediterranean plants, the assessment
      of neuroprotective properties of Laurus nobilis L. was of interest. Dried leaves
      were extracted by sonication using CHCl3 as solvent. The CHCl3 parental extract
      (CHCl3-pe) was fractionated to yield CHCl3 (LnC-1), EtOAc (LnC-2), MeOH (LnC-3)
      fractions. Each fraction underwent an extensive screening towards human
      neuroblastoma (SK-N-BE(2)-C, and SH-SY5Y) and rat glioma (C6) cell lines. MTT and
      SRB cytotoxicity tests were performed. The effect on the plasma membrane
      integrity was evaluated by assessment of LDH release. The caspase-3 activation
      enzyme and DNA fragmentation were also evaluated. The oxidant/antioxidant ability
      of all the extracts were evaluated using different methods. Furthermore, a
      metabolite profiling of the investigated extracts was carried out by GC-EI-MS.
      CHCl3-pe contained terpenes, allylphenols, and alpha-tocopherol. Dehydrocostus
      lactone was the main constituent. As result of the fractionation technique, the
      LnC-1 extract was mainly composed of alpha-tocopherol, whereas the LnC-2 fraction
      was enriched in guaiane and eudesmane terpenes. The most cytotoxic LnC-2 fraction
      induced apoptosis; it was ineffective in preventing in vitro free radicals
      production. Overall, the experimental results support a possible role of LnC-2
      preparation as a chemopreventive agent for neuronal cells or other cells of the
      CNS. 

PMID- 24095961
TI  - Improvement in the visual discrimination of recombinant clones by size reduction
      of non-recombinant colonies.
AB  - A flexible approach circumventing cloning problems related to incomplete vector
      double digest is described. DNA methyltransferase gene insertion into MCS of
      commonly used expression vectors facilitates identification of both: i) the
      correct linear fragment in agarose gels due to the dilator effect, and ii)
      recombinant colonies by size and opacity differences resulting from
      methyltransferase toxicity. 

PMID- 24095962
TI  - Cross-domain targeted ontology subsets for annotation: the case of SNOMED CORE
      and RxNorm.
AB  - The benefits of using ontology subsets versus full ontologies are well-documented
      for many applications. In this study, we propose an efficient subset extraction
      approach for a domain using a biomedical ontology repository with mappings, a
      cross-ontology, and a source subset from a related domain. As a case study, we
      extracted a subset of drugs from RxNorm using the UMLS Metathesaurus, the NDF-RT
      cross-ontology, and the CORE problem list subset of SNOMED CT. The extracted
      subset, which we termed RxNorm/CORE, was 4% the size of the full RxNorm (0.4%
      when considering ingredients only). For evaluation, we used CORE and RxNorm/CORE
      as thesauri for the annotation of clinical documents and compared their
      performance to that of their respective full ontologies (i.e., SNOMED CT and
      RxNorm). The wide range in recall of both CORE (29-69%) and RxNorm/CORE (21-35%)
      suggests that more quantitative research is needed to assess the benefits of
      using ontology subsets as thesauri in annotation applications. Our approach to
      subset extraction, however, opens a door to help create other types of clinically
      useful domain specific subsets and acts as an alternative in scenarios where well
      established subset extraction techniques might suffer from difficulties or cannot
      be applied. 

PMID- 24095963
TI  - A role for glutathione, independent of oxidative stress, in the developmental
      toxicity of methanol.
AB  - Oxidative stress and reactive oxygen species (ROS) have been implicated in the
      teratogenicity of methanol (MeOH) in rodents, both in vivo and in embryo culture.
      We explored the ROS hypothesis further in vivo in pregnant C57BL/6J mice.
      Following maternal treatment with a teratogenic dose of MeOH, 4 g/kg via
      intraperitoneal (ip) injection on gestational day (GD) 12, there was no increase
      6h later in embryonic ROS formation, measured by 2',7'-dichlorodihydrofluorescin
      diacetate (DCFH-DA) fluorescence, despite an increase observed with the positive
      control ethanol (EtOH), nor was there an increase in embryonic oxidatively
      damaged DNA, quantified as 8-oxo-2'-deoxyguanosine (8-oxodG) formation. MeOH
      teratogenicity (primarily ophthalmic anomalies, cleft palate) also was not
      altered by pre- and post-treatment with varying doses of the free radical spin
      trapping agent alpha-phenyl-N-tert-butylnitrone (PBN). In contrast, pretreatment
      with L-buthionine-(S,R)-sulfoximine (BSO), an inhibitor of glutathione (GSH)
      synthesis, depleted maternal hepatic and embryonic GSH, and enhanced some new
      anomalies (micrognathia, agnathia, short snout, fused digits, cleft lip, low set
      ears), but not the most common teratogenic effects of MeOH (ophthalmic anomalies,
      cleft palate) in this strain. These results suggest that ROS did not contribute
      to the teratogenic effects of MeOH in this in vivo mouse model, in contrast to
      results in embryo culture from our laboratory, and that the protective effect of
      GSH in this model may arise from its role as a cofactor for formaldehyde
      dehydrogenase in the detoxification of formaldehyde.

PMID- 24095964
TI  - Decontamination solutions for polychlorinated biphenyls (PCBs) in raw fish oils
      from environmentally contaminated sea fishes.
AB  - Fish oil has been identified as one of the most important contributors to the
      levels of polychlorinated biphenyls (PCBs) in food and feed products. In this
      study, PCB adsorption from fish oil onto activated carbon (AC), other sustainable
      adsorbents (mussel shell and wood waste ashes) and organic solvent such as
      ethanol were compared and optimized. Regarding to adsorbents, PCBs were extracted
      from fish oil by a 2.0% adsorbent material dose, during 6.0 h at 25  degrees C.
      Solvent extraction was carried out using 2 * 5.0 mL ethanol by manually stirring
      for 3.0 min, and then by Ultrasound-Assisted Solvent Extraction (UASE) for 5.0
      min. The results showed that removal rates obtained by using adsorbent materials
      ranged from 0.0 to 10% for marker PCBs, from 0.0 to 37% for mono-ortho-PCBs, from
      0.0 to 74% for PCB11 and from 0.0 to 95% for non-ortho-PCBs. Regarding to solvent
      extraction, ethanol was used by manually stirring and then by Ultrasound-Assisted
      Solvent Extraction (UASE). The samples were then centrifuged (2000 rpm/10 min)
      and the alcoholic phase was removed. With this method, removal efficiencies were
      much better (85-116%); nevertheless, high eicosapentaenoic acid (EPA) and
      docosahexaenoic acid (DHA) removal rates (70-78 and 71-79%, respectively) were
      detected. We can conclude that adsorption with adsorbents depends on the geometry
      of PCB congeners, as well as both type of adsorption material and their origin,
      and that several sorption cycles are needed. Adsorption with ethanol could be the
      most effective methodology but nutritional quality was impaired, what makes
      necessary to look for other not so polar removal solvents.

PMID- 24095965
TI  - Impact of humic/fulvic acid on the removal of heavy metals from aqueous solutions
      using nanomaterials: a review.
AB  - Nowadays nanomaterials have been widely used to remove heavy metals from
      water/wastewater due to their large surface area and high reactivity. Humic acid
      (HA) and fulvic acid (FA) exist ubiquitously in aquatic environments and have a
      variety of functional groups which allow them to complex with metal ions and
      interact with nanomaterials. These interactions can not only alter the
      environmental behavior of nanomaterials, but also influence the removal and
      transportation of heavy metals by nanomaterials. Thus, the interactions and the
      underlying mechanisms involved warrant specific investigations. This review
      outlined the effects of HA/FA on the removal of heavy metals from aqueous
      solutions by various nanomaterials, mainly including carbon-based nanomaterials,
      iron-based nanomaterials and photocatalytic nanomaterials. Moreover, mechanisms
      involved in the interactions were discussed and potential environmental
      implications of HA/FA to nanomaterials and heavy metals were evaluated. 

PMID- 24095966
TI  - Development and review of Euro 5 passenger car emission factors based on
      experimental results over various driving cycles.
AB  - The emissions of CO2 and regulated pollutants (NOx, HC, CO, PM) of thirteen Euro
      5 compliant passenger cars (seven gasoline, six Diesel) were measured on a
      chassis dynamometer. The vehicles were driven repeatedly over the European type
      approval driving cycle (NEDC) and the more dynamic WMTC and CADC driving cycles.
      Distance-specific emission factors were derived for each pollutant and sub-cycle,
      and these were subsequently compared to the corresponding emission factors
      provided by the reference European models used for vehicle emission inventory
      compilation (COPERT and HBEFA) and put in context with the applicable European
      emission limits. The measured emissions stayed below the legal emission limits
      when the type-approval cycle (NEDC) was used. Over the more dynamic cycles
      (considered more representative of real-world driving) the emissions were
      consistently higher but in most cases remained below the type-approval limit. The
      high NOx emissions of Diesel vehicles under real-world driving conditions remain
      the main cause for environmental concern regarding the emission profile of Euro 5
      passenger cars. Measured emissions of NOx exceeded the type-approval limits (up
      to 5 times in extreme cases) and presented significantly increased average values
      (0.35 g/km for urban driving and 0.56 g/km for motorway driving). The comparison
      with the reference models showed good correlation in all cases, a positive
      finding considering the importance of these tools in emission monitoring and
      policy-making processes.

PMID- 24095967
TI  - Exhaust emissions of volatile organic compounds of powered two-wheelers: effect
      of cold start and vehicle speed. Contribution to greenhouse effect and
      tropospheric ozone formation.
AB  - Powered two-wheeler (PTW) vehicles complying with recent European type approval
      standards (stages Euro 2 and Euro 3) were tested on chassis dynamometer in order
      to measure exhaust emissions of about 25 volatile organic compounds (VOCs) in the
      range C1-C7, including carcinogenic compounds as benzene and 1,3-butadiene. The
      fleet consists of a moped (engine capacity <= 50 cm(3)) and three fuel injection
      motorcycles of different engine capacities (150, 300 and 400 cm(3)). Different
      driving conditions were tested (US FPT cycle, constant speed). Due to the poor
      control of the combustion and catalyst efficiency, moped is the highest pollutant
      emitter. In fact, fuel injection strategy and three way catalyst with lambda
      sensor are able to reduce VOC motorcycles' emission of about one order of
      magnitude with respect to moped. Cold start effect, that is crucial for the
      assessment of actual emission of PTWs in urban areas, was significant: 30-51% of
      extra emission for methane. In the investigated speed range, moped showed a
      significant maximum of VOC emission factor at minimum speed (10 km/h) and a
      slightly decreasing trend from 20 to 60 km/h; motorcycles showed on the average a
      less significant peak at 10 km/h, a minimum at 30-40 km/h and then an increasing
      trend with a maximum emission factor at 90 km/h. Carcinogenic VOCs show the same
      pattern of total VOCs. Ozone Formation Potential (OFP) was estimated by using
      Maximum Incremental Reactivity scale. The greatest contribution to tropospheric
      ozone formation comes from alkenes group which account for 50-80% to the total
      OFP. VOC contribution effect on greenhouse effect is negligible with respect to
      CO2 emitted.

PMID- 24095968
TI  - Modelling the fate of nonylphenolic compounds in the Seine River--part 2:
      assessing the impact of global change on daily concentrations.
AB  - This study aims at modelling the daily concentrations of nonylphenolic compounds
      such as 4-nonylphenol (4-NP), nonylphenol monoethoxylate (NP1EO) and nonylphenoxy
      acetic acid (NP1EC) within the Seine River downstream of Paris City for over a
      year, firstly in the present state (year 2010) and for years 2050 and 2100 in
      order to assess the consequences of global change on the fate of nonylphenolic
      compounds in the Seine river. Concentrations were first simulated for the year
      2010 and compared to monthly measured values downstream of Paris. To achieve this
      goal, the hydrodynamic and biogeochemical model, ProSe, was updated to simulate
      the fate of 4-NP, NP1EO and NP1EC. The Seine upstream and Oise River (tributaries
      of the Seine River) concentrations are estimated according to concentrations-flow
      relationships. For Seine Aval wastewater treatment plant (SA-WWTP), the
      concentrations are considered constant and the median values of 11 campaigns are
      used. The biodegradation kinetics of 4-NP, NP1EO and NP1EC in the Seine River
      were deduced from the results of the companion paper. The Nash-Sutcliffe
      coefficient indicates a good efficiency to simulate the concentrations of 4-NP,
      NP1EC and NP1EO over an entire year. Eight scenarios were built to forecast the
      impacts of global warming (flow decrease), population growth (SA-WWTP flow
      increase) and optimisation of wastewater treatment (improvement of the quality of
      effluents) on annual concentrations of 4-NP, NP1EO and NP1EC at Meulan by 2050
      and 2100. As a result, global warming and population growth may increase the
      concentrations of 4-NP, NP1EC and NP1EO, especially during low-flow conditions,
      while the optimisation of wastewater treatment is an efficient solution to
      balance the global change by reducing WWTP outflows. 

PMID- 24095969
TI  - Runoff characteristics and nutrient loss mechanism from plain farmland under
      simulated rainfall conditions.
AB  - In recent years, nonpoint source (NPS) pollution has become the main contributor
      to water quality problems. Research on nitrogen (N) and phosphorus (P) losses
      from farmland and the factors that influence these losses is very meaningful both
      for increasing the crop yield and for improving environmental water quality. To
      explore the mechanism by which N and P are lost from farmland in the North China
      Plain (NCP), 16 simulated rainfalls were conducted in 14 experimental fields
      (each of which had different conditions) in the NCP from July to August in 2010.
      The results showed that the rainfall intensity, the antecedent soil moisture
      content, and the vegetation cover status were the main factors that affected the
      surface runoff in the NCP. The runoff volume increased with the increasing
      rainfall intensity and the increasing soil moisture content, and decreased with
      the increasing vegetation cover. These factors also significantly affected the
      losses of P and N. The losses of P and N were positively correlated with the
      rainfall intensity and the antecedent soil moisture content, and negatively
      correlated with the vegetation cover. A longer and more intense rainfall resulted
      in a higher loss of N and P. Dissolved nitrogen was the predominant form of N
      loss. For phosphorous, the predominant loss form was greatly influenced by the
      rainfall intensity, the vegetation cover, and the antecedent soil moisture
      content. Most of phosphorus existed as dissolved phosphorus in Baizhuang (BZ) and
      as particulate phosphorus in Tangcheng (TC) and Fentai (FT). The minimum
      requirements for runoff occurrence in experimental regions were a rainfall depth
      of 5.1mm, a rainfall intensity of 50mm/h, and an antecedent soil moisture of
      approximately 29.6%. 

PMID- 24095970
TI  - On the classification and sub-classification of aerosol key types over south
      central peninsular India: MODIS-OMI algorithm.
AB  - Long-term (8 years), simultaneous data on aerosol optical properties from MODIS
      and OMI satellite sensors are analyzed to study their temporal characteristics
      and to infer on the major aerosol types present over the study location,
      Bangalore situated in south central peninsular India. Investigations are carried
      out on Aerosol Optical Depths (AODs), Angstrom exponent (alpha) and Aerosol Index
      (AI) for the purpose. Aerosol parameters exhibited significant seasonal
      variations: AODs peaking during monsoon, alpha during post-monsoon and AI during
      summer. Seasonal air mass back trajectories are computed to infer on the
      transport component over the study region. By assigning proper thresholds
      (depending on the nature of the location and transport pathways) on AOD and alpha
      values, aerosols are discriminated into their major types viz., marine
      influenced, desert dust, urban/industrialized and mixed types. Further sub
      categorization of the aerosols has been done on an annual scale taking into
      account of their absorptance information in terms of the OMI-AI values. Mixed
      type aerosols contributed the most during all the seasons. Next to mixed type
      aerosols, marine influenced aerosols dominated during winter, desert dust during
      monsoon and summer, urban/industrialized aerosols during post-monsoon.
      Considering the urban nature of the study location,
      urban/industrialized/carbonaceous type aerosols have been significantly
      underestimated in these methodologies. Finally, discussion has been made on the
      consistency of the results obtained from the methodologies (i) based on AODs and
      alpha; (ii) based on AODs, alpha and AI.

PMID- 24095971
TI  - A mathematical model of pulse-coded hormone signal responses in pituitary
      gonadotroph cells.
AB  - Cells in the pituitary that synthesize luteinizing and follicle-stimulating
      hormones regulate the relative production of these two key reproductive hormones
      in response to signals from the hypothalamus. These signals are encoded in the
      frequency of gonadotrophin-releasing-hormone pulses. In vitro experiments with a
      murine-derived cell line have identified key elements of the processes that
      decode the signal to regulate transcription of the subunits encoding these
      hormones. The mathematical model described in this paper is based on the results
      of those experiments and advances quantitative understanding of the biochemical
      decoder. The model consists of non-linear differential equations for each of six
      processes that lead to the synthesis of follicle-stimulating hormone. Simulations
      of the model exhibit key characteristics found in the experiments, including a
      preference for follicle-stimulating hormone synthesis at low pulse frequencies
      and a loss of this characteristic when a mutation is introduced. 

PMID- 24095973
TI  - Quality measures for colonoscopy: a critical evaluation.
AB  - In a recent article in The New York Times, "The $2.7 Trillion Medical Bill,"(1)
      colonoscopy was singled out for its cost. In their response, the leading
      gastroenterology professional societies highlighted colonoscopy's effectiveness
      and cost-effectiveness for the prevention of colorectal cancer (CRC). Affirming
      colonoscopy's central role in CRC prevention, both as a frontline test and as the
      final common pathway for other CRC screening modalities, requires strategies to
      measure and improve colonoscopy quality, particularly by controlling operator
      dependent factors. Although colonoscopy is a powerful CRC screening test,(2-6)
      several recent studies have highlighted decreased protection, mainly against
      right-sided CRC,(5,7-16) an observation that has been linked to performance
      quality. 

PMID- 24095972
TI  - Detection of preclinically latent hyperperfusion due to stroke-like episodes by
      arterial spin-labeling perfusion MRI in MELAS patients.
AB  - In stroke-like episodes (SEs) of patients with mitochondrial myopathy,
      encephalopathy, lactic acidosis and stroke-like episodes (MELAS), the detection
      of preclinically latent lesions is a challenge. We report regional cerebral
      hyperperfusion observed on arterial spin labeling (ASL) perfusion magnetic
      resonance imaging (MRI) in the preclinical phase more than 3 months before the
      clinical onset of SEs in 3 MELAS patients. These hyperperfused areas were not
      detected by conventional MRI in the preclinical phase and developed into acute
      lesions at the clinical onset of SEs, suggesting that ASL imaging has the
      potential for predicting the emergence of SEs. 

PMID- 24095974
TI  - Factors that affect accuracy of alpha-fetoprotein test in detection of
      hepatocellular carcinoma in patients with cirrhosis.
AB  - BACKGROUND & AIMS: Measurements of alpha-fetoprotein (AFP) detect hepatocellular
      carcinoma (HCC) with low levels of sensitivity and specificity, and therefore are
      not recommended for use in liver cancer surveillance. However, AFP levels might
      accurately detect HCC in subgroups of patients. We performed a retrospective case
      control study to identify features of patients with cirrhosis in whom levels of
      AFP correlated with HCC. METHODS: We collected data from patients with cirrhosis,
      with (n = 452) or without (n = 676) HCC, diagnosed at Parkland Hospital in
      Dallas, Texas, from January 2005 through June 2012. We determined sensitivities
      and specificities with which different levels of AFP identified those with HCC;
      multivariate logistic regression was used to associate accurate identification of
      HCC with patient features (age, sex, race/ethnicity, alcohol intake, smoking,
      etiology of cirrhosis, presence of decompensation, and laboratory test results).
      We assessed the overall accuracy of these factors in detecting HCC using receiver
      operator characteristic curve analysis and the Delong method. We calculated
      levels of AFP that detect HCC with the highest levels of sensitivity and
      specificity in subgroups using receiver operator characteristic analysis.
      RESULTS: The most common etiologies of cirrhosis were hepatitis C virus (HCV)
      infection (60%) and alcohol induced (22%). Nearly 11% of patients were human
      immunodeficiency virus (HIV)-positive. Levels of AFP greater than 20 ng/mL
      detected HCC with 70.1% sensitivity and 89.8% specificity. This AFP level
      identified patients with HCC with a c-statistic of 0.87 (95% confidence interval,
      0.85-0.89); it was significantly more accurate in HCV-negative patients than in
      HCV-positive patients (c-statistic, 0.89 vs 0.83; P = .007). AFP levels of 59
      ng/mL or greater most accurately detected HCC in patients with HCV-associated
      cirrhosis; levels of AFP of 11 ng/mL or greater accurately identified HCC in HCV
      negative patients. The level of AFP identified early stage HCC with a c-statistic
      of 0.62 (95% confidence interval, 0.58-0.66), and had a significantly higher
      level of accuracy for HIV-positive patients than for HIV-negative patients (c
      statistic, 0.81 vs 0.59; P < .001). CONCLUSIONS: Based on a retrospective
      analysis of data from patients with cirrhosis, with or without HCC, AFP level
      most accurately detects HCC in patients without HCV infection. It detects HCC
      with a high level of accuracy in patients with cirrhosis and HIV infection.

PMID- 24095975
TI  - Breath testing for small intestinal bacterial overgrowth: maximizing test
      accuracy.
AB  - The diagnosis of small intestinal bacterial overgrowth (SIBO) has increased
      considerably owing to a growing recognition of its association with common bowel
      symptoms including chronic diarrhea, bloating, abdominal distention, and the
      irritable bowel syndrome. Ideally, an accurate and objective diagnosis of SIBO
      should be established before initiating antibiotic treatment. Unfortunately, no
      perfect test exists for the diagnosis of SIBO. The current gold standard, small
      bowel aspiration and quantitative culture, is limited by its high cost, invasive
      nature, lack of standardization, sampling error, and need for dedicated
      infrastructure. Although not without shortcomings, hydrogen breath testing
      provides the simplest noninvasive and widely available diagnostic modality for
      suspected SIBO. Carbohydrates such as lactulose and glucose are the most widely
      used substrates in hydrogen breath testing, with glucose arguably providing
      greater testing accuracy. Lactose, fructose, and sorbitol should not be used as
      substrates in the assessment of suspected SIBO. The measurement of methane in
      addition to hydrogen can increase the sensitivity of breath testing for SIBO.
      Diagnostic accuracy of hydrogen breath testing in SIBO can be maximized by
      careful patient selection for testing, proper test preparation, and
      standardization of test performance as well as test interpretation. 

PMID- 24095976
TI  - Surrogate markers of free cortisol in cirrhotic patients: another step has been
      reached.

PMID- 24095977
TI  - Decreasing mortality from acute biliary diseases that require endoscopic
      retrograde cholangiopancreatography: a nationwide cohort study.
AB  - BACKGROUND & AIMS: The management of acute biliary diseases often involves
      endoscopic retrograde cholangiopancreatography (ERCP), but it is not clear
      whether this technique reduces mortality. We investigated whether mortality from
      acute biliary diseases that require ERCP has been reduced over time and explored
      factors associated with mortality. METHODS: We conducted a cohort study using the
      Nationwide Inpatient Sample (1998-2008). We identified hospitalizations for
      choledocholithiasis, cholangitis, and acute pancreatitis that involved ERCP.
      Multivariate analyses were used to determine the effects of time period, patient
      factors, hospital characteristics, features of the ERCP procedure, and types of
      cholecystectomies on mortality, length of stay, and costs. RESULTS: From 1998 to
      2008 there were 166,438 admissions for acute biliary conditions that met the
      inclusion criteria, corresponding to more than 800,000 patients nationwide.
      During this interval, mortality decreased from 1.1% to 0.6% (adjusted odds ratio
      [aOR], 0.7; 95% confidence interval [CI], 0.6-0.8), diagnostic ERCPs decreased
      from 28.8% to 10.0%, hospitals performing fewer than 100 ERCPs per year decreased
      from 38.4% to 26.9%, open cholecystectomies decreased from 12.4% to 5.8%, and
      unsuccessful ERCPs decreased from 6.3% to 3.2% (P < .0001 for all trends).
      Unsuccessful ERCP (aOR, 1.7; 95% CI, 1.4-2.2), open cholecystectomy (aOR, 3.4;
      95% CI 2.7-4.3), cholangitis (aOR, 1.9; 95% CI, 1.5-2.3), older age, having
      Medicare health insurance, and comorbidity were associated with increased
      mortality. CONCLUSIONS: In-hospital mortality from acute biliary conditions
      requiring ERCP in the United States has decreased over time. Reductions in the
      rate of unsuccessful ERCPs and open cholecystectomies are associated with this
      trend.

PMID- 24095979
TI  - Spectral modulation of frontal EEG during motor skill acquisition: a mobile EEG
      study.
AB  - This study investigates the modulation of frontal EEG dynamics with respect to
      progress in motor skill acquisition using a wireless EEG system with a single dry
      sensor. Participants were required to complete repeated trials of a computerized
      visual-motor task similar to mirror drawing while the EEG was collected. In each
      trial, task performance of the participants was summarized with a familiarity
      index which took into account the performance accuracy, completion rate and time.
      Our findings demonstrated that certain EEG power spectra decreased with an
      increase in motor task familiarity. In particular, frontal EEG activities in
      delta and theta bands of the whole trial and in gamma band in the middle of the
      trial are having a significant negative relationship with the overall familiarity
      level of the task. The findings suggest that frontal EEG spectra are
      significantly modulated during motor skill acquisition. Results of this study
      shed light on the possibility of simultaneous monitoring of brain activity during
      an unconstrained natural task with a single dry sensor mobile EEG in an everyday
      environment. 

PMID- 24095981
TI  - Pedunculopontine nucleus evoked potentials from subthalamic nucleus stimulation
      in Parkinson's disease.
AB  - The effects of subthalamic nucleus (STN) stimulation on the pedunculopontine
      nucleus area (PPNR) evoked activities were examined in two patients with
      Parkinson's disease. The patients had previously undergone bilateral STN deep
      brain stimulation (DBS) and subsequently received unilateral DBS electrodes in
      the PPNR. Evoked potentials were recorded from the local field potentials (LFP)
      from the PPNR with STN stimulation at different frequencies and bipolar contacts.
      Ipsilateral and contralateral short latency (<2ms) PPNR responses were evoked
      from left but not from right STN stimulation. In both patients, STN stimulation
      evoked contralateral PPNR responses at medium latencies between 41 and 45ms.
      Cortical evoked potentials to single pulse STN stimulation were observed at
      latencies between 18 and 27ms. These results demonstrate a functional connection
      between the STN and the PPNR. It likely involves direct projections between the
      STN and PPNR or polysynaptic pathways with thalamic or cortical relays. 

PMID- 24095980
TI  - Deletion in the N-terminal half of olfactomedin 1 modifies its interaction with
      synaptic proteins and causes brain dystrophy and abnormal behavior in mice.
AB  - Olfactomedin 1 (Olfm1) is a secreted glycoprotein that is preferentially
      expressed in neuronal tissues. Here we show that deletion of exons 4 and 5 from
      the Olfm1 gene, which encodes a 52 amino acid long region in the N-terminal part
      of the protein, increased neonatal death and reduced body weight of surviving
      homozygous mice. Magnetic resonance imaging analyses revealed reduced brain
      volume and attenuated size of white matter tracts such as the anterior
      commissure, corpus callosum, and optic nerve. Adult Olfm1 mutant mice
      demonstrated abnormal behavior in several tests including reduced marble digging,
      elevated plus maze test, nesting activity and latency on balance beam tests as
      compared with their wild-type littermates. The olfactory system was both
      structurally and functionally disturbed by the mutation in the Olfm1 gene as
      shown by functional magnetic resonance imaging analysis and a smell test.
      Deficiencies of the olfactory system may contribute to the neonatal death and
      loss of body weight of Olfm1 mutant. Shotgun proteomics revealed 59 candidate
      proteins that co-precipitated with wild-type or mutant Olfm1 proteins in
      postnatal day 1 brain. Olfm1-binding targets included GluR2, Cav2.1, teneurin-4
      and Kidins220. Modified interaction of Olfm1 with binding targets led to an
      increase in intracellular Ca(2+) concentration and activation of ERK1/2, MEK1 and
      CaMKII in the hippocampus and olfactory bulb of Olfm1 mutant mice compared with
      their wild-type littermates. Excessive activation of the CaMKII and Ras-ERK
      pathways in the Olfm1 mutant olfactory bulb and hippocampus by elevated
      intracellular calcium may contribute to the abnormal behavior and olfactory
      activity of Olfm1 mutant mice. 

PMID- 24095982
TI  - Application of high-throughput sequencing for studying genomic variations in
      congenital heart disease.
AB  - Congenital heart diseases (CHD) represent the most common birth defect in human.
      The majority of cases are caused by a combination of complex genetic alterations
      and environmental influences. In the past, many disease-causing mutations have
      been identified; however, there is still a large proportion of cardiac
      malformations with unknown precise origin. High-throughput sequencing
      technologies established during the last years offer novel opportunities to
      further study the genetic background underlying the disease. In this review, we
      provide a roadmap for designing and analyzing high-throughput sequencing studies
      focused on CHD, but also with general applicability to other complex diseases.
      The three main next-generation sequencing (NGS) platforms including their
      particular advantages and disadvantages are presented. To identify potentially
      disease-related genomic variations and genes, different filtering steps and gene
      prioritization strategies are discussed. In addition, available control datasets
      based on NGS are summarized. Finally, we provide an overview of current studies
      already using NGS technologies and showing that these techniques will help to
      further unravel the complex genetics underlying CHD. 

PMID- 24095978
TI  - The Janus face of the heme oxygenase/biliverdin reductase system in Alzheimer
      disease: it's time for reconciliation.
AB  - Alzheimer disease (AD) is the most common form of dementia among the elderly and
      is characterized by progressive loss of memory and cognition. These clinical
      features are due in part to the increase of reactive oxygen and nitrogen species
      that mediate neurotoxic effects. The up-regulation of the heme oxygenase
      1/biliverdin reductase-A (HO-1/BVR-A) system is one of the earlier events in the
      adaptive response to stress. HO-1/BVR-A reduces the intracellular levels of pro
      oxidant heme and generates equimolar amounts of the free radical scavengers
      biliverdin-IX alpha (BV)/bilirubin-IX alpha (BR) as well as the pleiotropic
      gaseous neuromodulator carbon monoxide (CO) and ferrous iron. Two main and
      opposite hypotheses for a role of the HO-1/BVR-A system in AD propose that this
      system mediates neurotoxic and neuroprotective effects, respectively. This
      apparent controversy was mainly due to the fact that for over about 20years HO-1
      was the only player on which all the analyses were focused, excluding the other
      important and essential component of the entire system, BVR. Following studies
      from the Butterfield laboratory that reported alterations in BVR activity along
      with decreased phosphorylation and increased oxidative/nitrosative post
      translational modifications in the brain of subjects with AD and amnestic mild
      cognitive impairment (MCI) subjects, a debate was opened on the real
      pathophysiological and clinical significance of BVR-A. In this paper we provide a
      review of the main discoveries about the HO/BVR system in AD and MCI, and propose
      a mechanism that reconciles these two hypotheses noted above of neurotoxic and
      the neuroprotective aspects of this important stress responsive system. 

PMID- 24095983
TI  - The nature of the carbohydrate binding module determines the catalytic efficiency
      of xylanase Z of Clostridium thermocellum.
AB  - Xylanase Z of Clostridium thermocellum exists as a complex in the cellulosome
      with N-terminus feruloyl esterase, a carbohydrate binding module (CBM6) and a
      dockerin domain. To study the role of the binding modules on the activity of
      XynZ, different variants with the CBM6 attached to the catalytic domain at its C
      terminal (XynZ-CB) and N-terminal (XynZ-BC), and the CBM22 attached at N-terminus
      (XynZ-B'C) were expressed in Escherichia coli at levels around 30% of the total
      cell proteins. The activities of XynZ-BC, XynZ-CB and XynZ-B'C were 4200, 4180
      and 20,700U MUM(-1) against birchwood xylan, respectively. Substrate binding
      studies showed that in case of XynZ-BC and XynZ-CB the substrate birchwood xylan
      remaining unbound were 51 and 52%, respectively, whereas in the case of XynZ-B'C
      the substrate remaining unbound was 39% under the assay conditions used. The
      molecular docking studies showed that the binding site of CBM22 in XynZ-B'C is
      more exposed and thus available for substrate binding as compared to the tunnel
      shape binding pocket produced in XynZ-BC and thus hindering the substrate
      binding. The substrate binding data for the two constructs are in agreement with
      this explanation.

PMID- 24095984
TI  - Effect of fluoride varnish supplemented with sodium trimetaphosphate on enamel
      erosion and abrasion: an in situ/ex vivo study.
AB  - OBJECTIVE: To evaluate the effect of fluoride (F) varnishes supplemented or not
      with sodium trimetaphosphate (TMP) on enamel erosive wear followed or not by
      abrasion in situ. METHODS: Ten volunteers were selected and randomly divided into
      four groups, according to the varnishes tested: placebo (no F or TMP), 5% NaF
      (positive control), 2.5% NaF and 2.5% NaF/5% TMP. Enamel blocks (n=4) were
      mounted in palatal devices and received an application of each test varnish,
      following a double-blind, crossover protocol. After 6h, varnishes were completely
      removed and the blocks were subjected to erosive challenges by ex vivo immersion
      in citric acid (5 min, 4*/dia, 5 days). Following, half of the blocks were
      subjected to abrasion by brushing with a placebo dentifrice slurry for 15s.
      Enamel wear (MUm), surface hardness (SHf) and cross-sectional hardness (DeltaKHN)
      were assessed after each experimental period. Results were analyzed by ANOVA,
      Student-Newman-Keuls's test and Pearson correlation coefficient (p<0.05).
      RESULTS: The fluoride varnish supplemented with TMP promoted significantly lower
      wear and DeltaKHN when compared to the other groups after erosive challenges,
      followed or not by abrasion (p<0.05). As for (SHf) the fluoride varnish
      supplemented with TMP promoted similar results to the 5% NaF product, being
      significantly higher than the remaining groups after erosive and erosive+abrasive
      challenges (p<0.05). CONCLUSION: TMP significantly enhanced the effects of F on
      enamel wear after erosive challenges, followed or not by abrasion.

PMID- 24095985
TI  - Effect of three-year consumption of erythritol, xylitol and sorbitol candies on
      various plaque and salivary caries-related variables.
AB  - OBJECTIVE: The objective of the present paper is to report results from oral
      biologic studies carried out in connection with a caries study. METHODS: Samples
      of whole-mouth saliva and dental plaque were collected from initially 7- to 8
      year-old subjects who participated in a 3-year school-based programme
      investigating the effect of the consumption of polyol-containing candies on
      caries rates. The subjects were randomized in three cohorts, consumed erythritol,
      xylitol, or sorbitol candies. The daily polyol consumption from the candies was
      approximately 7.5 g. RESULTS: A significant reduction in dental plaque weight
      from baseline (p<0.05) occurred in the erythritol group during almost all
      intervention years while no changes were found in xylitol and sorbitol groups.
      Usage of polyol candies had no significant or consistent effect on the levels of
      plaque protein, glucose, glycerol, or calcium, determined yearly in connection
      with caries examinations. After three years, the plaque of erythritol-receiving
      subjects contained significantly (p<0.05) lower levels of acetic acid and
      propionic acid than that of subjects receiving xylitol or sorbitol. Lactic acid
      levels partly followed the same pattern. The consumption of erythritol was
      generally associated with significantly (p<0.05) lower counts of salivary and
      plaque mutans streptococci compared with the other groups. There was no change in
      salivary Lactobacillus levels. CONCLUSION: Three-year consumption of erythritol
      containing candies by initially 7- to 8-year old children was associated with
      reduced plaque growth, lower levels of plaque acetic acid and propionic acid, and
      reduced oral counts of mutans streptococci compared with the consumption of
      xylitol or sorbitol candies.

PMID- 24095986
TI  - CD4+CD25+ regulatory T cells-derived exosomes prolonged kidney allograft survival
      in a rat model.
AB  - CD4(+)CD25(+) regulatory T cells (Tregs) are negative regulators of the immune
      system that induce and maintain immune tolerance. Exosomes are natural products
      released from many sources and play a role in antigen presentation,
      immunoregulation, and signal transduction. In order to determine whether exosomes
      can be released from Tregs and participate in transplantation tolerance, we
      isolated and purified Tregs-derived exosomes and established a rat model of
      kidney transplantation. We then transferred the autologous exosomes into
      recipients to observe the effect of transplantation tolerance in vivo and in
      vitro. From in vivo study, serum analysis and histology showed that the function
      of exosomes can postpone allograft rejection and prolong the survival time of
      transplanted kidney. From in vitro study, exosomes possessed the capacity to
      suppress T cells proliferation. Taken together, these results suggest that the
      Tregs-derived exosomes have a suppressive role on acute rejection and inhibit T
      cells proliferation, especially exosomes derived from donor-type Tregs, which
      imply that the Tregs-derived exosomes are one of far-end regulation mechanisms of
      Tregs. Thus, exosomes released from Tregs could be considered as a possible
      immunosuppressive reagent for the treatment of transplant rejection. 

PMID- 24095987
TI  - Membrane surface functionalization via theophylline derivative coating and
      streptavidin immobilization.
AB  - Poly(vinylidene fluoride) (PVDF) and regenerated cellulose (RC) membranes were
      surface-modified by the adsorption of one adenosine receptor antagonist: the
      theophylline-oligo(ethylene glycol)-alkene derivative, Theo1. Surface
      modification was carried out by immersion of the membrane in a dichloromethane
      solution of Theo1 (PVDF+Theo1 and RC+Theo1 samples). Membrane surfaces with
      partial coverage by theophylline and/or its inclusion in the membrane structures
      were studied by X-ray photoelectron spectroscopy (XPS), solid-state nuclear
      magnetic resonance (SNMR), impedance spectroscopy (IS) and contact angle (CA)
      measurements. The Theo1 orientation was inferred from the data. Streptavidin (SA)
      was immobilized onto the membrane/Theo1 hybrid material. The protein-theophylline
      Theo1 interaction was visualized with bright field microscopy (BFM). 

PMID- 24095988
TI  - Conformational changes in human plasma proteins induced by metal oxide
      nanoparticles.
AB  - The interaction of nanoparticles (Nps) with body fluids may induce conformational
      changes in the proteins present in the medium. Such interactions could induce
      functional loss or important modifications in some proteins, and trigger cellular
      events induced by the Np-protein moiety. As metal oxide nanoparticles are widely
      used for various applications, the interaction of four different metal oxide Nps
      (ZnO, TiO2, CeO2 and Al2O3) with three of the main protein fractions from human
      plasma (albumin, fibrinogen and globulins) was characterized by fluorescence and
      Fourier-transform infrared (FTIR) spectroscopy. The pattern of Np-protein
      interaction was shown to vary depending on the type of Np. For ZnO Nps, a strong
      interaction was observed, which induced a decrease in the thermal stability of
      both fibrinogen and albumin at a low temperature, interfering with the clotting
      activity of fibrinogen. TiO2 and CeO2 Nps showed lower effects, while for Al2O3
      Nps only a slight or null interaction was observed at physiological pH. Moreover,
      the influence of pH was characterized for albumin, showing that the Np-protein
      interaction has an important dependence on the Np surface charge. The
      conformational changes induced by metal oxide Nps in the secondary structure of
      albumin are principally the transformation of alpha-helices into beta-sheet
      structures. The interaction, with the exception of Al2O3 nanoparticles at basic
      pH, could take place in the domain II of the protein, formed mainly by
      hydrophobic and positive residues. 

PMID- 24095989
TI  - Topographic analysis of the development of individual activation patterns during
      performance monitoring in medial frontal cortex.
AB  - Age-related improvements in human performance monitoring have been linked to
      maturation of medial frontal cortex (MFC) in healthy youth, however, imaging
      studies conflict regarding age-related changes in MFC activation patterns.
      Topographical analysis of single-subject activation enables measurement of
      variation in location of MFC activation by age, as well as other potentially
      influential factors (e.g., performance on task). In this study, 22 youth (ages 8
      17 years) and 21 adults (ages 23-51 years) underwent functional magnetic
      resonance imaging during a performance monitoring task examining interference and
      errors. Single-subject factors (extent of MFC activation, age and accuracy) were
      entered into a three-level hierarchical linear model to test the influence of
      these characteristics on location of MFC activation. Activation shifted from a
      rostral/anterior to a more dorsal/posterior location with increasing age and
      accuracy during interference. Inclusion of age and accuracy accounted for almost
      all of the unexplained variance in location of interference-related activation
      within MFC. This pattern links improvement of performance-monitoring capacity to
      age-related increases in posterior MFC and decreases in anterior MFC activation.
      Taken together, these results show the maturation of performance monitoring
      capacity to depend on more focal engagement of posterior MFC substrate for
      cognitive control. 

PMID- 24095990
TI  - [125I]AT-1012, a new high affinity radioligand for the alpha3beta4 nicotinic
      acetylcholine receptors.
AB  - Recent genetic and pharmacological studies have implicated the alpha3, beta4 and
      alpha5 subunits of the nicotinic acetylcholine receptor (nAChR) in dependence to
      nicotine and other abused drugs and nicotine withdrawal. The alpha3beta4* nAChR
      subtype has been shown to co-assemble with the alpha5 or beta3 nAChR subunits,
      and is found mainly in the autonomic ganglia and select brain regions. It has
      been difficult to study the alpha3beta4 nAChR because there have been no
      selective nonpeptidic ligands available to independently examine its
      pharmacology. We recently reported the synthesis of a [(125)I]-radiolabeled
      analog of a high affinity, selective small-molecule alpha3beta4 nAChR ligand, AT
      1012. We report here the vitro characterization of this radioligand in receptor
      binding and in vitro autoradiographic studies targeting the alpha3beta4* nAChR.
      Binding of [(125)I]AT-1012 was characterized at the rat alpha3beta4 and
      alpha4beta2 nAChR transfected into HEK cells, as well as at the human
      alpha3beta4alpha5 nAChR in HEK cells. Binding affinity of [(125)I]AT-1012 at the
      rat alpha3beta4 nAChR was 1.4 nM, with a B(max) of 10.3 pmol/mg protein, similar
      to what was determined for unlabeled AT-1012 using [(3)H]epibatidine. Saturation
      isotherms suggested that [(125)I]AT-1012 binds to a single site on the
      alpha3beta4 nAChR. Similar high binding affinity was also observed for [(125)I]AT
      1012 at the human alpha3beta4alpha5 nAChR transfected into HEK cells. [(125)I]AT
      1012 did not bind with high affinity to membranes from alpha4beta2 nAChR
      transfected HEK cells. Binding studies with [(3)H]epibatidine further confirmed
      that AT-1012 had over 100-fold binding selectivity for alpha3beta4 over
      alpha4beta2 nAChR. K(i) values determined for known nAChR compounds using
      [(125)I]AT-1012 as radioligand were comparable to those obtained with
      [(3)H]epibatidine. [(125)I]AT-1012 was also used to label alpha3beta4 nAChR in
      rat brain slices in vitro using autoradiography, which showed highly localized
      binding of the radioligand in brain regions consistent with the discreet
      localization of the alpha3beta4 nAChR. We demonstrate that [(125)I]AT-1012 is an
      excellent tool for labeling the alpha3beta4 nAChR in the presence of other nAChR
      subtypes.

PMID- 24095991
TI  - Probabilistic spill occurrence simulation for chemical spills management.
AB  - Inland chemical spills pose a great threat to water quality in worldwide area. A
      sophisticated probabilistic spill-event model that characterizes temporal and
      spatial randomness and quantifies statistical uncertainty due to limited spill
      data is a major component in spill management and associated decision making.
      This paper presents a MATLAB-based Monte Carlo simulation (MMCS) model for
      simulating the probabilistic quantifiable occurrences of inland chemical spills
      by time, magnitude, and location based on North America Industry Classification
      System codes. The model's aleatory and epistemic uncertainties were quantified
      through integrated bootstrap resampling technique. Benzene spills in the St.
      Clair River area of concern were used as a case to demonstrate the model by
      simulating spill occurrences, occurrence time, and mass expected for a 10-year
      period. Uncertainty analysis indicates that simulated spill characteristics can
      be described by lognormal distributions with positive skewness. The simulated
      spill time series will enable a quantitative risk analysis for water quality
      impairments due to the spills. The MMCS model can also help governments to
      evaluate their priority list of spilled chemicals. 

PMID- 24095992
TI  - Enhanced photocatalytic degradation of humic acids using Al and Fe co-doped TiO2
      nanotubes under UV/ozonation for drinking water purification.
AB  - O3/UV/TiO2 was used to effectively decompose humic acids (HAs) in drinking water.
      To obtain a large specific surface area and low band gap energy, Al and Fe co
      doped TiO2 nanotubes were successfully synthesized using the hydrothermal method.
      The effect of the optimal co-doped TiO2 nanotubes catalyst on the HAs removal
      efficiency through O3/UV/co-doped TiO2 process was investigated. The highest HAs
      removal efficiency (79.4%) that exhibited a pseudo-first-order rate constant of
      0.172 min(-1) was achieved, in the presence of 550  degrees C calcined 1.0% co
      doped TiO2 nanotubes with an Al:Fe ratio of 0.25:0.75. The effects of calcination
      temperature and doping concentration on anatase phase weight fractions, average
      crystallite sizes, Brunauer-Emmett-Teller surface area, catalyst band gap energy,
      and catalyst photocatalytic activity were also discussed. The inorganic anions
      also affected the catalyst photocatalytic ability. In a neutral solution, SO4(2-)
      slightly promoted HAs removal. However, HCO3(-) was found to significantly
      inhibit the catalyst activity, whereas Cl(-) had negligible effect on
      photocatalytic ability.

PMID- 24095993
TI  - Sustainable nitrate-contaminated water treatment using multi cycle ion
      exchange/bioregeneration of nitrate selective resin.
AB  - The sustainability of ion-exchange treatment processes using high capacity single
      use resins to remove nitrate from contaminated drinking water can be achieved by
      regenerating the exhausted resin and reusing it multiple times. In this study,
      multi cycle loading and bioregeneration of tributylamine strong base anion (SBA)
      exchange resin was studied. After each cycle of exhaustion, biological
      regeneration of the resin was performed using a salt-tolerant, nitrate
      perchlorate-reducing culture for 48 h. The resin was enclosed in a membrane to
      avoid direct contact of the resin with the culture. The results show that the
      culture was capable of regenerating the resin and allowing the resin to be used
      in multiple cycles. The concentrations of nitrate in the samples reached a peak
      in first 0.5-1h after placing the resin in medium because of desorption of
      nitrate from resin with desorption rate of 0.099 +/- 0.003 hr(-1). After this
      time, since microorganisms began to degrade the nitrate in the aqueous phase, the
      nitrate concentration was generally non-detectable after 10h. The average of
      calculated specific degradation rate of nitrate was -0.015 mg NO3(-)/mg VSS h.
      Applying 6 cycles of resin exhaustion/regeneration shows resin can be used for 4
      cycles without a loss of capacity, after 6 cycles only 6% of the capacity was
      lost. This is the first published research to examine the direct regeneration of
      a resin enclosed in a membrane, to allow reuse without any disinfection or
      cleaning procedures.

PMID- 24095994
TI  - An amperometric NO2 sensor based on La10Si5NbO27.5 electrolyte and nano
      structured CuO sensing electrode.
AB  - A novel amperometric-type NO2 sensor based on La10Si5NbO27.5 (LSNO) electrolyte
      and nano-structured CuO sensing electrode was fabricated and tested. A bilayer
      LSNO electrolyte including both a dense layer and a porous layer was prepared by
      conventional solid state reaction method and screen-printing technology. The nano
      structured CuO sensing electrode was in situ fabricated in LSNO porous layer by
      impregnating method. The composition and microstructure of the sample were
      characterized by XRD and SEM, respectively. The results showed that the CuO
      particles with diameters range of 200-500 nm were homogeneously dispersed on the
      LSNO backbone in porous layer. The sensor exhibited well sensing characteristics
      to NO2. The response current was almost linear to NO2 concentration in the range
      of 25-500 ppm at 600-800  degrees C. With increase of operating temperature, the
      sensitivity increased and reached 297 nA/ppm at 800  degrees C. The response
      currents toward NO2 were slightly affected by coexistent O2 (0-21 vol%) and CO2
      (0-5 vol%).

PMID- 24095995
TI  - Fungal permeable reactive barrier to remediate groundwater in an artificial
      aquifer.
AB  - Biobarriers, as permeable reactive barriers (PRBs), are a common technology that
      mainly uses bacteria to remediate groundwater in polluted aquifers. In this
      study, we propose to use Trametes versicolor, a white-rot fungus, as the reactive
      element because of its capacity to degrade a wide variety of highly recalcitrant
      and xenobiotic compounds. A laboratory-scale artificial aquifer was constructed
      to simulate groundwater flow under real conditions in shallow aquifers. Orange G
      dye was chosen as a contaminant to visually monitor the hydrodynamic behaviour of
      the system and any degradation of the dye by the fungus. Batch experiments at
      different pH values (6 and 7) and several temperatures (15  degrees C, 18 
      degrees C, 20  degrees C and 25  degrees C) were performed to select the
      appropriate residence time and glucose consumption rate required for continuous
      treatment. The maximum Orange G degradation was 97%. Continuous degradation over
      85% was achieved for more than 8 days. Experimental results indicate for the
      first time that this fungus can potentially be used as a permeable reactive
      barrier in real aquifers.

PMID- 24095996
TI  - Influence of the application of chelant EDDS on soil enzymatic activity and
      microbial community structure.
AB  - The present study evaluated the effects of a biodegradable chelant, S,S
      ethylenediaminedisuccinic acid (EDDS), on enzyme activities and microbial
      community composition in copper (Cu)-contaminated soils, planted with either corn
      or beans. Results showed that the application of EDDS did not affect urease and
      acid phosphatase activities in the soil, but greatly reduced catalase and
      saccharase activities, and increased beta-glucosidase activity on the seventh day
      after EDDS application. On the 28th day, no significant difference was observed
      in the enzyme activities (except for beta-glucosidase) of EDDS-treated soils
      compared to the controls. Analysis of phospholipid fatty acids (PLFAs) showed
      that the application of 3 mmol kg(-1) EDDS did not cause significant stress to
      soil microbial communities. However, PCR-denaturing gradient gel electrophoresis
      (PCR-DGGE) fingerprint revealed that EDDS influenced the bacterial communities in
      the soils, and the effects on bean soils were more significant than that with
      corn. In general, the enzyme activities and bacterial communities were influenced
      by the application of EDDS, but the impact became weaker or even disappeared with
      the biodegradation of EDDS.

PMID- 24095997
TI  - Novel metabolites in cyanobacterium Cylindrospermopsis raciborskii with potencies
      to inhibit gap junctional intercellular communication.
AB  - Despite intensive research into toxic bloom-forming cyanobacteria, the majority
      of their metabolites remain unknown. The present study explored in detail a novel
      bioactivity identified in cyanobacteria, i.e. inhibition of gap junctional
      intercellular communication (GJIC), a marker of tumor promotion. The
      extracellular mixture (exudate) of the cyanobacterial strain Cylindrospermopsis
      raciborskii (SAG 1.97) was fractionated by semi-preparative reversed phase HPLC,
      and the fractions assessed for their potencies to inhibit GJIC. Two non-polar
      fractions that significantly inhibited GJIC were further fractionated, tested and
      analyzed using multiple mass spectrometric methods. Investigations led to the
      identification of a putative chemical compound (molecular formula C18H34O3, m/z
      299.2581 for the [M+H](+) ion) responsible for observed bioactivities. Specific
      inhibitors of signaling pathways were used to screen for biochemical mechanisms
      beyond GJIC inhibition, and the results indicate the involvement of ERK1/2
      kinases via a mechanism related to the action of epidermal growth factor EGF but
      clearly distinct from other anthropogenic tumor promoters like polychlorinated
      biphenyls or polycyclic aromatic hydrocarbons. The chemical and in vitro
      toxicological characterizations of the newly described metabolite provide
      important insights into the still poorly understood health impacts of complex
      toxic cyanobacterial blooms and indicate that currently applied monitoring
      practices may underestimate actual risks. 

PMID- 24095998
TI  - Simultaneous decolorization of reactive Orange M2R dye and reduction of chromate
      by Lysinibacillus sp. KMK-A.
AB  - Azo dyes constitute the largest and diverse group of dyes, widely used in number
      of industries that are contributing toward organic and inorganic load of effluent
      treatment. In the present study, Lysinibacillus sp. KMK-A was able to effectively
      decolorize Orange M2R dye up to 2000 mg l(-1) (Vmax of 19.6 mg l(-1) h(-1) and Km
      of 439 mg l(-1)) and reduce Cr(VI) up to 250 mg l(-1) (Vmax of 3.6 mg l(-1) h(-1)
      and Km 28.3 mg l(-1)). It also has an ability of simultaneous decolorization of
      Orange M2R dye (200-1000 mg l(-1)) with reduction of Cr(VI) (50-200 mg l(-1)).
      Significant reduction in total organic carbon content, chemical and biological
      oxygen demand along with spectroscopic and chromatographic analysis confirmed the
      biotransformation of Orange M2R. Involvement of enzymes namely azoreductase and
      chromate reductase was observed during biotransformation. The phyto and geno
      toxicity studies demonstrated that metabolites of dye degradation were non-toxic.
      Higher tolerance with simultaneous decolorization and detoxification of azo dyes
      in presence of Cr(VI) makes Lysinibacillus sp. KMK-A, a potential candidate for
      eco-friendly remediation of metal contaminated dye effluents.

PMID- 24095999
TI  - Adsorptive removal of dibenzothiophene from model fuels over one-pot synthesized
      PTA@MIL-101(Cr) hybrid material.
AB  - Hybrid nanomaterials comprising phosphotungstic acid (PTA) and MIL-101(Cr) were
      prepared through one-pot synthesis and post-modification methods and then were
      used as adsorbents of dibenzothiophene (DBT) from simulated diesel fuels. Samples
      obtained by different ways (encapsulation and impregnation) were characterized by
      nitrogen adsorption, transmission electron microscope (TEM), X-ray diffraction
      (XRD), Fourier transform infrared spectrum (FT-IR) and series of adsorption
      experiments. The equilibrium adsorption capacities of PTA@MIL-101(Cr) illustrated
      that the direct introduction of PTA into MIL-101(Cr) during synthesis resulted in
      a 10.7% increase compared with MIL-101(Cr). However, porous hybrid adsorbent
      PTA/MIL-101(Cr) prepared via post-modification method exhibited lower adsorption
      capacity than virgin MIL-101(Cr). The theoretical maximum adsorption capacity
      (Q0) of PTA@MIL-101(Cr) is 136.5mg S/g adsorbent, 4.2 times of MIL-101(Cr). Even
      in competitive adsorption between aromatic compounds, which possess strong
      affinity with MOFs, and DBT, PTA@MIL-101(Cr) and MIL-101(Cr) remained their
      effectiveness in removal of DBT in the system. Based on these results, it can be
      presumed that MIL-101(Cr), modified properly, can be used as a promising
      adsorbent for eliminating aromatics and S-compounds in commercial fuels
      simultaneously. 

PMID- 24096000
TI  - Microbial dechlorination activity during and after chemical oxidant treatment.
AB  - Potassium permanganate (PM) and sodium persulfate (PS) are used in soil
      remediation, however, their compatibility with a coinciding or subsequent
      biotreatment is poorly understood. In this study, different concentrations of PM
      (0.005-2g/L) and PS (0.01-4.52 g/L) were applied and their effects on the
      abundance, activity, and reactivation potential of a dechlorinating enrichment
      culture were investigated. Expression of the tceA, vcrA and 16S rRNA genes of
      Dehalococcoides spp. were detected at 0.005-0.01 g/L PM and 0.01-0.02 g/L PS.
      However, with 0.5-2g/L PM and 1.13-4.52 g/L PS no gene expression was recorded,
      neither were indicator molecules for total cell activity (Adenosine triphosphate,
      ATP) detected. Dilution did not promote the reactivation of the microbial cells
      when the redox potential was above -100 mV. Similarly, inoculated cells did not
      dechlorinate trichloroethene (TCE) above -100 mV. When the redox potential was
      decreased to -300 mV and the reactors were bioaugmented for a second time,
      dechlorination activity recovered, but only in the reactors with 1.13 and 2.26
      g/L PS. In conclusion, our results show that chemical oxidants can be combined
      with a biotreatment at concentrations below 0.5 g/L PM and 1g/L PS.

PMID- 24096001
TI  - Nitrate removal from groundwater driven by electricity generation and
      heterotrophic denitrification in a bioelectrochemical system.
AB  - This research aims to develop a new approach for in situ nitrate removal from
      groundwater by using a bioelectrochemical system (BES). The BES employs
      bioelectricity generated from organic compounds to drive nitrate moving from
      groundwater into the anode and reduces nitrate to nitrogen gas by heterotrophic
      denitrification. This laboratory study of a bench-scale BES demonstrated
      effective nitrate removal from both synthetic and actual groundwater. It was
      found that applying an electrical potential improved the nitrate removal and the
      highest nitrate removal rate of 208.2 +/- 13.3g NO3(-)-Nm(-3) d(-1) was achieved
      at 0.8 V. Although the open circuit condition (no electricity generation) still
      resulted in a nitrate removal rate of 158.5 +/- 4.2 gm(-3) d(-1) due to ion
      exchange, electricity production could inhibit ion exchange and prevent
      introducing other undesired ions into groundwater. The nitrate removal rate
      exhibited a linear relationship with the initial nitrate concentration in
      groundwater. The BES produced a higher current density of 33.4 Am(-3) and a
      higher total coulomb of 244.7 +/- 9.1C from the actual groundwater than the
      synthetic groundwater, likely because other ions in the actual groundwater
      promoted ion movement to assist electricity generation. Further development of
      this BES will need to address several key challenges in anode feeding solution,
      ion competition, and long-term stability.

PMID- 24096002
TI  - Screening protein--single stranded RNA complexes by NMR spectroscopy for
      structure determination.
AB  - In the past few years, RNA molecules have been revealed to be at the center of
      numerous biological processes. Long considered as passive molecules transferring
      genetic information from DNA to proteins, it is now well established that RNA
      molecules play important regulatory roles. Associated with that, the number of
      identified RNA binding proteins (RBPs) has increased considerably and mutations
      in RNA molecules or RBP have been shown to cause various diseases, such as
      cancers. It is therefore crucial to understand at the molecular level how these
      proteins specifically recognise their RNA targets in order to design new
      generation drug therapies targeting protein-RNA complexes. Nuclear magnetic
      resonance (NMR) is a particularly well-suited technique to study such protein-RNA
      complexes at the atomic level and can provide valuable information for new drug
      discovery programs. In this article, we describe the NMR strategy that we and
      other laboratories use for screening optimal conditions necessary for structural
      studies of protein-single stranded RNA complexes, using two proteins, Sam68 and T
      STAR, as examples. 

PMID- 24096003
TI  - High-resolution profiling of protein occupancy on polyadenylated RNA transcripts.
AB  - A key prerequisite to understand how gene regulatory processes are controlled by
      the interplay of RNA-binding proteins and ribonucleoprotein complexes with RNAs
      is the generation of comprehensive high-resolution maps of protein-RNA
      interactions. Recent advances in next-generation sequencing technology
      accelerated the development of various crosslinking and immunoprecipitation
      (CLIP) approaches to broadly identify RNA regions contacted by RNA-binding
      proteins. However these methods only consider single RNA-binding proteins and
      their contact sites, irrespective of the overall cis-regulatory sequence space
      contacted by other RNA interacting factors. Here we describe the application of
      protein occupancy profiling, a novel approach that globally displays the RNA
      contact sites of the poly(A)+ RNA-bound proteome. Protein occupancy profiling
      enables the generation of transcriptome-wide maps of protein-RNA interactions on
      polyadenylated transcripts and narrows the sequence search space for transcript
      regions involved in cis-regulation of gene expression in response to internal or
      external stimuli, altered cellular programs or disease. 

PMID- 24096004
TI  - A novel KCNQ1 missense mutation identified in a patient with juvenile-onset
      atrial fibrillation causes constitutively open IKs channels.
AB  - BACKGROUND: Atrial fibrillation (AF) is one of the most common cardiac
      arrhythmias. In some patients, the disease is inheritable; however, hereditary
      aspects of AF remain not fully elucidated. OBJECTIVE: The purpose of this study
      was to identify genetic backgrounds that contribute to juvenile-onset AF and to
      define the mechanism. METHODS: In 30 consecutive juvenile-onset AF patients
      (onset age <50 years), we screened AF-related genes (KCNQ1, KCNH2, KCNE1-3,
      KCNE5, KCNJ2, SCN5A). We analyzed the function of mutant channels using whole
      cell patch-clamp techniques and computer simulations. RESULTS: Among the juvenile
      onset AF patients, we identified three mutations (10%): SCN5A-M1875T, KCNJ2
      M301K, and KCNQ1-G229D. Because KCNQ1 variant (G229D) identified in a 16-year-old
      boy was novel, we focused on the proband. The G229D-IKs was found to induce a
      large instantaneous activating component without deactivation after
      repolarization to -50 mV. In addition, wild-type (WT)/G229D-IKs (WT and mutant
      coexpression) displayed both instantaneous and time-dependent activating
      currents. Compared to WT-IKs, the tail current densities in WT/G229D-IKs were
      larger at test potentials between -130 and -40 mV but smaller at test potentials
      between 20 and 50 mV. Moreover, WT/G229D-IKs resulted in a negative voltage shift
      for current activation (-35.2 mV) and slower deactivation. WT/G229D-IKs conducted
      a large outward current induced by an atrial action potential waveform, and
      computer simulation incorporating the WT/G229D-IKs results revealed that the
      mutation shortened atrial but not ventricular action potential. CONCLUSION: A
      novel KCNQ1-G229D mutation identified in a juvenile-onset AF patient altered the
      IKs activity and kinetics, thereby increasing the arrhythmogenicity to AF.

PMID- 24096006
TI  - Histone acetyltransferase p300 promotes MKL1-mediated transactivation of catechol
      O-methyltransferase gene.
AB  - Previous studies have revealed that histone acetyltransferase p300 is recruited
      to the promoters of certain cardiac and smooth muscle specific genes to enhance
      the transactivation activity of myocardin, which is a master regulator in
      cardiovascular differentiation and development. Here, we found that the gene
      encoding catechol-O-methyltransferase (COMT), an important metabolic enzyme
      catalyzing the conversion of estrogen, is also a target gene of myocardin-related
      transcription factors (MRTFs). Megakaryoblastic leukemia 1 (MKL1, also named MRTF
      A) and p300 could synergistically augment the expression of COMT gene, increase
      the metabolic rate of estrogen, and thus reduce the proliferation of MCF-7 breast
      cancer cells stimulated by estrogen. 

PMID- 24096005
TI  - DCLK1 marks a morphologically distinct subpopulation of cells with stem cell
      properties in preinvasive pancreatic cancer.
AB  - BACKGROUND & AIMS: As in other tumor types, progression of pancreatic cancer may
      require a functionally unique population of cancer stem cells. Although such
      cells have been identified in many invasive cancers, it is not clear whether they
      emerge during early or late stages of tumorigenesis. Using mouse models and human
      pancreatic cancer cell lines, we investigated whether preinvasive pancreatic
      neoplasia contains a subpopulation of cells with distinct morphologies and cancer
      stem cell-like properties. METHODS: Pancreatic tissue samples were collected from
      the KC(Pdx1), KPC(Pdx1), and KC(iMist1) mouse models of pancreatic
      intraepithelial neoplasia (PanIN) and analyzed by confocal and electron
      microscopy, lineage tracing, and fluorescence-activated cell sorting.
      Subpopulations of human pancreatic ductal adenocarcinoma (PDAC) cells were
      similarly analyzed and also used in complementary DNA microarray analyses.
      RESULTS: The microtubule regulator DCLK1 marked a morphologically distinct and
      functionally unique population of pancreatic cancer-initiating cells. These cells
      displayed morphological and molecular features of gastrointestinal tuft cells.
      Cells that expressed DCLK1 also expressed high levels of ATAT1, HES1, HEY1,
      IGF1R, and ABL1, and manipulation of these pathways in PDAC cell lines inhibited
      their clonogenic potential. Pharmacological inhibition of gamma-secretase
      activity reduced the abundance of these cells in murine PanIN in a manner that
      correlated with inhibition of PanIN progression. CONCLUSIONS: Human PDAC cells
      and pancreatic neoplasms in mice contain morphologically and functionally
      distinct subpopulations that have cancer stem cell-like properties. These
      populations can be identified at the earliest stages of pancreatic tumorigenesis
      and provide new cellular and molecular targets for pancreatic cancer treatment
      and/or chemoprevention.

PMID- 24096007
TI  - Are hungry sheep more pessimistic? The effects of food restriction on cognitive
      bias and the involvement of ghrelin in its regulation.
AB  - Food restriction is considered to be a welfare issue in extensively reared
      animals. However, the effects of food restriction on the affective state, and its
      physiological regulation, are unknown. In Experiment 1, we aimed to assess the
      effects of increased plasma concentrations of acyl-ghrelin on judgement bias (an
      indicator of affective states) by fasting sheep for 24h or by ghrelin
      administration. In Experiment 2, we aimed to assess the effects of chronic food
      restriction on judgement bias and attention bias towards a food-related cue. For
      the judgement bias test, sheep were trained in an arena to approach a positive
      location cue associated with conspecifics and not approach a negative location
      cue associated with a dog. Three non-trained, non-reinforced ambiguous location
      cues were situated between the positive and negative locations. Attention bias
      towards a food-related cue was assessed by placing an empty food bucket against
      the wall of the arena halfway between the entry point and the positive location.
      In Experiment 1, sheep were divided into three treatments; 24h fast, ghrelin
      administration or control. Judgement bias, locomotor activity and plasma cortisol
      concentrations were assessed. The ghrelin treated group tended to express a more
      pessimistic bias compared to the control group (P<0.1), and plasma cortisol
      concentrations tended to be increased (P<0.1). In Experiment 2, sheep were
      subjected to a high feeding level (HF) or low feeding level (LF) for 7days. The
      LF group tended to show a more optimistic judgement bias (P<0.1). When the food
      related cue was presented, LF ewes took longer to reach the positive location
      (P<0.001), spent longer with their head inside the bucket (P<0.001) and more time
      interacting with the bucket (P<0.01). This study provides preliminary evidence
      that food restriction alters judgement bias and attention bias towards a food
      related cue which may indicate altered affective states of sheep. 

PMID- 24096009
TI  - Genome-wide association and sequencing studies on colorectal cancer.
AB  - Colorectal cancer is a leading cause of morbidity and mortality worldwide.
      Understanding its genetic mechanisms is key to improving risk prediction,
      prognostication and treatment. Results from genome-wide association studies have
      engendered a growing list of colorectal cancer susceptibility genes whereas the
      application of genome-wide mutational analysis has enabled the depiction of
      mutational landscape of colorectal cancer at high resolution. The development of
      novel technologies, such as metagenomic and single-cell sequencing, is expected
      to have positive impact on future genetic studies. However, challenges remain to
      address the changing epidemiology of colorectal cancer, issues on genetic
      testing, and clinical utilization of genomic data. 

PMID- 24096008
TI  - Basal ganglia morphology links the metabolic syndrome and depressive symptoms.
AB  - The metabolic syndrome (MetS) is a clustering of cardiovascular and
      cerebrovascular risk factors that are often comorbid with depressive symptoms.
      Individual components of the MetS also covary with the morphology of basal
      ganglia regions that are altered by depression. However, it remains unknown
      whether the covariation between the MetS and depressive symptomatology can be
      accounted for in part by morphological changes in the basal ganglia. Accordingly,
      we tested the hypothesis that increased depressive symptoms among individuals
      with the MetS might be statistically mediated by reduced gray matter volume in
      basal ganglia regions. The presence of the MetS was determined in 147 middle-aged
      adults using the criteria of the National Cholesterol Education Program, Adult
      Treatment Panel III. Basal ganglia volumes were determined on an a priori basis
      by automated segmentation of high-resolution magnetic resonance images.
      Depressive symptoms were assessed using the Patient Health Questionnaire. Even
      after controlling for demographic and other confounding factors, having the MetS
      and meeting more MetS criteria covaried with reduced globus pallidus volume.
      Meeting more MetS criteria and reduced pallidal volume were also related to
      depressive symptoms. Moreover, the MetS-depression association was statistically
      mediated by pallidal volume. In summary, reduced globus pallidus volume is a
      neural correlate of the MetS that may partly account for its association with
      depressive symptoms. 

PMID- 24096010
TI  - Chronic toxicity of the veterinary antibiotic florfenicol to Daphnia magna
      assessed at two temperatures.
AB  - The hypothesis that temperature variation is able to modify the chronic toxicity
      of the antibiotic florfenicol (FLO) to Daphnia magna was tested in the present
      study. Twenty-one day laboratory bioassays were carried out at 20 and 25  degrees
      C. FLO concentrations and its potential decay during the assays were checked by
      spectrophotometry. At 20  degrees C, FLO significantly reduced the D. magna
      somatic growth (>=1.6 mg/L) and impaired its reproduction (EC20=6.9 mg/L;
      EC50=7.6 mg/L), with the population growth rate becoming negative at 12.6 mg/L.
      At 25  degrees C, the EC values were lower (1.7 and 1.9 mg/L, respectively) than
      at 20  degrees C, as well as the lowest exposure concentration causing a negative
      population growth rate (3.1 mg/L). These results clearly indicate that
      temperature raise from 20 to 25  degrees C was able to modify the FLO toxicity.
      Therefore, more studies on the combined effects of temperature changes and
      environmental contaminants are needed to improve the basis for ecological risk
      assessment, environmental and human safety.

PMID- 24096011
TI  - A la carte defibrillation poised to enter the fixed price resuscitation menu.

PMID- 24096012
TI  - Pattern recognition and probabilistic measures in alignment-free sequence
      analysis.
AB  - With the massive production of genomic and proteomic data, the number of
      available biological sequences in databases has reached a level that is not
      feasible anymore for exact alignments even when just a fraction of all sequences
      is used. To overcome this inevitable time complexity, ultrafast alignment-free
      methods are studied. Within the past two decades, a broad variety of nonalignment
      methods have been proposed including dissimilarity measures on classical
      representations of sequences like k-words or Markov models. Furthermore, articles
      were published that describe distance measures on alternative representations
      such as compression complexity, spectral time series or chaos game
      representation. However, alignments are still the standard method for real world
      applications in biological sequence analysis, and the time efficient alignment
      free approaches are usually applied in cases when the accustomed algorithms turn
      out to fail or be too inconvenient. 

PMID- 24096013
TI  - Hydrogen peroxide-responsive copolyoxalate nanoparticles for detection and
      therapy of ischemia-reperfusion injury.
AB  - The main culprit in the pathogenesis of ischemia/reperfusion (I/R) injury is the
      generation of high level of hydrogen peroxide (H2O2). In this study, we report a
      novel diagnostic and therapeutic strategy for I/R injury based on H2O2
      activatable copolyoxalate nanoparticles using a murine model of hind limb I/R
      injury. The nanoparticles are composed of hydroxybenzyl alcohol (HBA)
      incorporating copolyoxalate (HPOX) that, in the presence of H2O2, degrades
      completely into three known and safe compounds, cyclohexanedimethanol, HBA and
      CO2. HPOX effectively scavenges H2O2 in a dose-dependent manner and hydrolyzes to
      release HBA which exerts intrinsic antioxidant and anti-inflammatory activities
      both in vitro and in vivo models of hind limb I/R. HPOX nanoparticles loaded with
      fluorophore effectively and robustly image H2O2 generated in hind limb I/R
      injury, demonstrating their potential for bioimaging of H2O2-associated diseases.
      Furthermore, HPOX nanoparticles loaded with anti-apoptotic drug effectively
      release the drug payload after I/R injury, exhibiting their effectiveness for a
      targeted drug delivery system for I/R injury. We anticipate that multifunctional
      HPOX nanoparticles have great potential as H2O2 imaging agents, therapeutics and
      drug delivery systems for H2O2-associated diseases. 

PMID- 24096015
TI  - In vitro targeting and imaging the translocator protein TSPO 18-kDa through G(4)
      PAMAM-FITC labeled dendrimer.
AB  - Mitochondria represent an attractive subcellular target due to its function
      particularly important for oxidative damage, calcium metabolism and apoptosis.
      However, the concept of mitochondrial targeting has been a neglected area so far.
      The translocator protein (TSPO) represents an interesting subcellular target not
      only to image disease states overexpressing this protein, but also for a
      selective mitochondrial drug targeting. Recently, we have delivered in vitro and
      in vivo small molecule imaging agents into cells overexpressing TSPO by using a
      family of high-affinity conjugable ligands characterized by 2-phenyl-imidazo[1,2
      a]pyridine acetamide structure. As an extension, in the present work we studied
      the possibility to target and image TSPO with dendrimers. These nano-platforms
      have unique features, in fact, are prepared with a level of control not reachable
      with most linear polymers, leading to nearly monodisperse, globular
      macromolecules with a large number of peripheral groups. As a consequence, they
      are an ideal delivery vehicle candidate for explicit study of the effects of
      polymer size, charge, composition, and architecture on biologically relevant
      properties such as lipid bilayer interactions, cytotoxicity, cellular
      internalization, and subcellular compartments and organelles interactions. Here,
      we present the synthesis, characterization, cellular internalization, and
      mitochondria labeling of a TSPO targeted fourth generation [G(4)-PAMAM] dendrimer
      nanoparticle labeled with the organic fluorescent dye fluorescein. We
      comprehensively studied the cellular uptake behavior of these dendrimers, into
      glioma C6 cell line, under the influence of various endocytosis inhibitors. We
      found that TSPO targeted-G(4)-PAMAM-FITC dendrimer is quickly taken up by these
      cells by endocytosis pathways, and moreover specifically targets the mitochondria
      as evidenced from subcellular fractionation experiments and co-localization
      studies performed with CAT (Confocal-AFM-TIRF) microscopy. 

PMID- 24096016
TI  - Rubik-like magnetic nanoassemblies as an efficient drug multifunctional carrier
      for cancer theranostics.
AB  - A practical and effective strategy for loading hydrophobic anticancer agents
      within the inside and outside oleic acid layer of Rubik-like magnetic
      nanoassemblies (MNAs) is established. In this strategy, four individual oleic
      acid-capped iron oxide nanocubes and dioleate-modified polyethylene glycol are
      assembled into cluster with high drug loading capability, high magnetism, as well
      as rapid and extended release behavior. After loading model drug paclitaxel
      (PTX), PTX-MNAs show greater antitumor activity both in vitro cell culture and in
      vivo animal trials compared with the same dose of free PTX (Taxol). With high
      uptake by tumor cells, MNAs exhibit in tumor imaging by magnetic resonance
      imaging. These outstanding properties are largely due to the drug delivery
      systems that take high drug-loading capability and high magnetism into
      consideration in a nano-dimension for maximizing the nanotheranostic functions
      and minimizing the toxic side effects. In summary, the Rubik-like magnetic
      nanoassemblies may have the potential to realize "all-in-one" nanotheranostic
      strategy to detect, diagnose, treat, and monitor tumors and therapeutic response
      in further pre-clinical and clinical studies. 

PMID- 24096014
TI  - Mind the gap: a survey of how cancer drug carriers are susceptible to the gap
      between research and practice.
AB  - With countless research papers using preclinical models and showing the
      superiority of nanoparticle design over current drug therapies used to treat
      cancers, it is surprising how deficient the translation of these nano-sized drug
      carriers into the clinical setting is. This review article seeks to compare the
      preclinical and clinical results for Doxil(r), PK1, Abraxane(r), Genexol-PM(r),
      XyotaxTM, NC-6004, Mylotarg(r), PK2, and CALAA-01. While not comprehensive, it
      covers nano-sized drug carriers designed to improve the efficacy of common drugs
      used in chemotherapy. While not always available or comparable, effort was made
      to compare the pharmacokinetics, toxicity, and efficacy between the animal and
      human studies. Discussion is provided to suggest what might be causing the gap.
      Finally, suggestions and encouragement are dispensed for the potential that nano
      sized drug carriers hold. 

PMID- 24096017
TI  - Controlled iodine release from polyurethane sponges for water decontamination.
AB  - Iodinated polyurethane (IPU) sponges were prepared by immersing sponges in
      aqueous/organic solutions of iodine or exposing sponges to iodine vapors. Iodine
      was readily adsorbed into the polymers up to 100% (w/w). The adsorption of iodine
      on the surface was characterized by XPS and SEM analyses. The iodine loaded IPU
      sponges were coated with ethylene vinyl acetate (EVA), in order to release iodine
      in a controlled rate for water decontamination combined with active carbon
      cartridge, which adsorbs the iodine residues after the microbial inactivation.
      The EVA coated IPU were incorporated in a water purifier and tested for iodine
      release to water and for microbial inactivation efficiency according to WQA
      certification program against P231/EPA for 250l, using 25l a day with flow rate
      of 6-8min/1l. The antimicrobial activity was also studied against Escherichia
      coli and MS2 phage. Bacterial results exceeded the minimal requirement for
      bacterial removal of 6log reduction throughout the entire lifespan. At any
      testing point, no bacteria was detected in the outlet achieving more than 7.1 to
      more than 8log reduction as calculated upon the inlet concentration. Virus
      surrogate, MS2, reduction results varied from 4.11log reduction under tap water,
      and 5.11log reduction under basic water (pH9) to 1.32 for acidic water (pH5).
      Controlled and stable iodine release was observed with the EVA coated IPU sponges
      and was effective in deactivating the bacteria and virus present in the
      contaminated water and thus, these iodinated PU systems could be used in water
      purification to provide safe drinking water. These sponges may find applications
      as disinfectants in medicine. 

PMID- 24096018
TI  - Polymer-filled microcontainers for oral delivery loaded using supercritical
      impregnation.
AB  - In the last years a large variety of drug delivery systems have been developed to
      improve bioavailability of therapeutics in oral administration. An increasing
      interest has arisen in reservoir-based microdevices designed for active
      ingredients like water insoluble compounds and fragile biomolecules. Such
      microdevices are designed to protect the active ingredient against degradation
      and deactivation, and to allow cytoadhesion and unidirectional drug release.
      There are few works which optimize the drug loading step and often therapeutics
      are dosed in the microdevices through laborious and time consuming procedures.
      This work proposes an effective loading technique for a poorly soluble model drug
      in microcontainers, by combining inkjet printing and supercritical fluid
      impregnation. Well defined quantities of poly(vinyl pyrrolidone) (PVP) solutions
      are dispensed into microcontainers by inkjet printing with a quasi-no-waste
      performance. Then ketoprofen is impregnated in the polymer matrix by using
      supercritical carbon dioxide (scCO2) as loading medium. The amount of polymer is
      controlled by the volume and the number of droplets of dispensed polymer and drug
      loading is tuned by varying the impregnation parameters. Compared to solid
      dispersions of the same drug and polymer, scCO2-impregnated microcontainers
      exhibit a more reproducible drug loading and a faster dissolution rate of the
      active compound which allows drug release to be modulated. The combination of
      these loading techniques potentially allows the high throughput fabrication of
      microdevices for oral drug delivery with a safe and solvent-free solution. 

PMID- 24096019
TI  - Targeted drug delivery with focused ultrasound-induced blood-brain barrier
      opening using acoustically-activated nanodroplets.
AB  - Focused ultrasound (FUS) in the presence of systemically administered
      microbubbles has been shown to locally, transiently and reversibly increase the
      permeability of the blood-brain barrier (BBB), thus allowing targeted delivery of
      therapeutic agents in the brain for the treatment of central nervous system
      diseases. Currently, microbubbles are the only agents that have been used to
      facilitate the FUS-induced BBB opening. However, they are constrained within the
      intravascular space due to their micron-size diameters, limiting the delivery
      effect at or near the microvessels. In the present study, acoustically-activated
      nanodroplets were used as a new class of contrast agents to mediate FUS-induced
      BBB opening in order to study the feasibility of utilizing these nanoscale phase
      shift particles for targeted drug delivery in the brain. Significant dextran
      delivery was achieved in the mouse hippocampus using nanodroplets at clinically
      relevant pressures. Passive cavitation detection was used in the attempt to
      establish a correlation between the amount of dextran delivered in the brain and
      the acoustic emission recorded during sonication. Conventional microbubbles with
      the same lipid shell composition and perfluorobutane core as the nanodroplets
      were also used to compare the efficiency of an FUS-induced dextran delivery. It
      was found that nanodroplets had a higher BBB opening pressure threshold but a
      lower stable cavitation threshold than microbubbles, suggesting that contrast
      agent-dependent acoustic emission monitoring was needed. A more homogeneous
      dextran delivery within the targeted hippocampus was achieved using nanodroplets
      without inducing inertial cavitation or compromising safety. Our results offered
      a new means of developing the FUS-induced BBB opening technology for potential
      extravascular targeted drug delivery in the brain, extending the potential drug
      delivery region beyond the cerebral vasculature. 

PMID- 24096020
TI  - ColoPulse tablets perform comparably in healthy volunteers and Crohn's patients
      and show no influence of food and time of food intake on bioavailability.
AB  - ColoPulse tablets are an innovative development in the field of oral drug
      delivery and are characterized by a colon-specific release. Until now ColoPulse
      dosage forms (only capsules) have been studied in healthy volunteers having a
      standardized breakfast three hours after administration but not in specific
      patient groups and not with a shorter interval between administration and
      breakfast. Information on bioavailability and release characteristics of
      ColoPulse tablets in Crohn's patients and the influence of food and time of food
      intake is a prerequisite to properly design future clinical studies with active
      substances in these patients. In the current cross-over study bioavailability and
      drug release characteristics of ColoPulse tablets were compared in healthy
      volunteers and in Crohn's patients in remission. Furthermore the influence of
      food and time of food intake on the in vivo drug release behavior of ColoPulse
      tablets was investigated. In this study the dual label isotope strategy was used
      which means that a ColoPulse tablet containing (13)C-urea and an uncoated,
      immediate release tablet containing (15)N2-urea were taken simultaneously. Breath
      and urine samples were collected during the test day for isotope analysis. The
      appearance of the stable isotopes in breath and/or urine provides information on
      the site of release from the dosage form, release characteristics and
      bioavailability. Both tablets were administered on two different days in a cross
      over design: the first day with a breakfast (non-standardized) one hour after
      administration and the second day with a standardized breakfast three hours after
      administration of the tablets. There was no difference in instructions for
      administration between both days. Results of 16 healthy volunteers and 14 Crohn's
      patients were evaluated. At least 86% (51 out of 59) of all ColoPulse tablets
      administered in this study released their contents at the desired intestinal
      region. There was no significant difference in bioavailability between healthy
      volunteers and Crohn's patients on both days (day 1 75.8% vs 90.2%, p=0.070 and
      day 2 83.4% vs 91.4%, p=0.265). There was also no significant influence of food
      and time of food intake on bioavailability in healthy volunteers (75.8% and
      83.4%, p=0.077) and in Crohn's patients (90.2% and 91.4%, p=0.618) when day 1 and
      day 2 were compared. Release characteristics did not significantly differ between
      healthy volunteers and Crohn's patients. However, food and time of food intake
      had some, clinically non-relevant, influence on the release characteristics
      within both groups which is in line with the fact that food affects gastro
      intestinal transit times. This study shows that ColoPulse tablets enable the site
      specific delivery of drugs or other compounds (e.g. diagnostics) deep in the ileo
      colonic region of the intestine of Crohn's patients in a comparable amount and
      rate as in healthy volunteers. Food and time of food intake had no relevant
      influence on bioavailability. In conclusion ColoPulse delivery systems are
      promising and deserve further research for local therapy with immunosuppressive
      drugs in Crohn's patients in the near future. 

PMID- 24096021
TI  - Gelatin-based nanoparticles as drug and gene delivery systems: reviewing three
      decades of research.
AB  - Gelatin is one of the most versatile natural biopolymers widely used in
      pharmaceutical industries due to its biocompatibility, biodegradability, low cost
      and numerous available active groups for attaching targeting molecules. These
      advantages led to its application in the synthesis of nanoparticles for drug and
      gene delivery during the last thirty years. The current article entails a general
      review of the different preparation techniques of gelatin nanoparticles (GNPs):
      desolvation, coacervation-phase separation, emulsification-solvent evaporation,
      reverse phase microemulsion, nanoprecipitation, self-assembly and layer-by-layer
      coating, from the point of view of the methodological and mechanistic aspects
      involved. Various crosslinkers used to improve the physicochemical properties of
      GNPs includintg aldehydes, genipin, carbodiimide/N-hydroxysuccinimide, and
      transglutaminase are reported. An analysis is given of the physicochemical
      behavior of GNPs including drug loading, release, particle size, zeta-potential,
      cytotoxicity, cellular uptake and stability. This review also attempts to provide
      an overview of the major applications of GNPs in drug delivery and gene therapy
      and their in vivo pharmacological performances, as well as site-specific drug
      targeting using various ligands modifying the surface of GNPs. Finally,
      nanocomplexes of gelatin with polymers, lipids or inorganic materials are also
      discussed. 

PMID- 24096022
TI  - The human topoisomerase 1B Arg634Ala mutation results in camptothecin resistance
      and loss of inter-domain motion correlation.
AB  - Human topoisomerase 1B, the unique target of the natural anticancer compound
      camptothecin, catalyzes the unwinding of supercoiled DNA by introducing transient
      single strand nicks and providing covalent protein-DNA adducts. The functional
      properties and the drug reactivity of the single Arg634Ala mutant have been
      investigated in comparison to the wild type enzyme. The mutant is characterized
      by an identical relaxation and cleavage rate but it displays resistance to
      camptothecin as indicated by a viability assay of the yeast cells transformed
      with the mutated protein. The mutant also displays a very fast religation rate
      that is only partially reduced by the presence of the drug, suggesting that this
      is the main reason for its resistance. A comparative analysis of the structural
      dynamical properties of the native and mutant proteins by molecular dynamics
      simulation indicates that mutation of Arg634 brings to a loss of motion
      correlation between the different domains and in particular between the linker
      and the C-terminal domain, containing the catalytic tyrosine residue. These
      results indicate that the loss of motion correlation and the drug resistance are
      two strongly correlated events. 

PMID- 24096023
TI  - Comparison of the catalytic properties of the botulinum neurotoxin subtypes A1
      and A5.
AB  - Clostridium botulinum neurotoxins (BoNTs) cause the life-threatening disease
      botulism through the inhibition of neurotransmitter release by cleaving essential
      SNARE proteins. There are seven serologically distinctive types of BoNTs and many
      subtypes within a serotype have been identified. BoNT/A5 is a recently discovered
      subtype of type A botulinum neurotoxin which possesses a very high degree of
      sequence similarity and identity to the well-studied A1 subtype. In the present
      study, we examined the endopeptidase activity of these two BoNT/A subtypes and
      our results revealed significant differences in substrate binding and cleavage
      efficiency between subtype A5 and A1. Distinctive hydrolysis efficiency was
      observed between the two toxins during cleavage of the native substrate SNAP-25
      versus a shortened peptide mimic. N-terminal truncation studies demonstrated that
      a key region of the SNAP-25, including the amino acid residues at 151 through 154
      located in the remote binding region of the substrate, contributed to the
      differential catalytic properties between A1 and A5. Elevated binding affinity of
      the peptide substrate resulted from including these important residues and
      enhanced BoNT/A5's hydrolysis efficiency. In addition, mutations of these amino
      acid residues affect the proteolytic performance of the two toxins in different
      ways. This study provides a better understanding of the biological activity of
      these toxins, their performance characteristics in the Endopep-MS assay to detect
      BoNT in clinical samples and foods, and is useful for the development of peptide
      substrates. 

PMID- 24096024
TI  - Splenic metastases from caecal carcinoma: Diagnostic considerations and
      therapeutic strategy.
AB  - INTRODUCTION: The spleen is a highly vascular organ and is in close proximity to
      many potential primary sites such as the stomach, breast, pancreas and colon. It
      is however an unusual site for metastatic disease. The reasons for this are not
      fully understood at the present time. A number of hypotheses have been
      postulated. Definitive diagnosis and subsequent treatment of metastatic disease
      to the spleen presents a number of challenges for the surgeon and the wider multi
      disciplinary team. PRESENTATION OF CASE: A 60 year old male presented with a
      three week history of lower abdominal pain, distension, nausea and a palpable
      mass in the right iliac fossa. Imaging revealed a large circumferential caecal
      mass consistent with malignancy with secondary small bowel obstruction. The
      patient underwent an emergency right hemicolectomy and was subsequently treated
      with systemic chemotherapy for lymph node positive caecal adenocarcinoma. Two
      years following initial presentation, two suspicious lesions were noted within
      the spleen during routine surveillance imaging with computerised tomography of
      the thorax, abdomen and pelvis. Of note, one month prior to this the patient had
      a normal surveillance colonoscopy performed with multiple interval
      carcinoembryonic antigen (CEA) levels recorded within the normal range. Image
      guided splenic biopsy and subsequent histology confirmed metastatic caecal
      adenocarcinoma. DISCUSSION: Splenic metastases from any source including the
      colon are a rare phenomenon. CONCLUSION: This case questions the value of routine
      post operative CEA monitoring, underlines the importance of multimodal pathways
      of surveillance and highlights recent advances in image guided splenic biopsy
      techniques.

PMID- 24096025
TI  - Reversible facial nerve palsy due to parotid abscess.
AB  - INTRODUCTION: A facial nerve palsy combined with parotid enlargement usually
      suggests malignancy. It is highly unusual for facial nerve palsy to result from a
      benign situation such as inflammation or infection of the gland. PRESENTATION OF
      CASE: We present a rare case of facial nerve palsy due to parotid abscess.
      DISCUSSION: A literature search retrieved thirty-two cases of facial nerve palsy
      due to benign parotid lesions since 1969. Only nine reported the presence of a
      parotid abscess. The etiology of paralysis remains unknown although certain
      factors such as the virulence of the offending organisms or perineuritis, have
      been suggested. Best diagnostic evaluation and management are discussed.
      CONCLUSION: In clinical practice, exclusion of malignancy is mandatory, as it
      represents the most common cause of facial palsy in the presence of a parotid
      lump.

PMID- 24096026
TI  - Co-liquefaction of micro- and macroalgae in subcritical water.
AB  - Co-liquefaction of microalgae (Spirulina platensis, SP) and macroalgae
      (Entermorpha prolifera, EP) was studied in subcritical water by using a stainless
      steel batch reactor at different temperature (250 to 370 degrees C), time (5 to
      120 min), SP/EP mass ratio (0 to 100%), and water/algae mass ratio (1:1 to 6:1).
      The results suggested that a positive synergetic effect existed during the co
      liquefaction of SP and EP, and this synergetic effect was dependent on reaction
      conditions. Co-liquefaction alleviated the severe reaction conditions compared to
      the separate liquefaction of SP and EP and also promoted the in situ
      deoxygenation of the bio-oil. The higher-heating-value of bio-oil produced from
      the co-liquefaction of SP and EP (wSP:wEP=1) is 35.3 MJ/kg. The energy recovery
      from the co-liquefaction is larger than the average value from the separate
      liquefaction of SP and EP. Co-liquefaction did not affect the molecular
      composition but affect the relative amount of each component in the bio-oil.

PMID- 24096027
TI  - Implicit emotion regulation in the presence of threat: neural and autonomic
      correlates.
AB  - Efficient emotion regulation is essential for social interaction and functioning
      in human society and often happens without direct intention and conscious
      awareness. Cognitive labeling of stimuli based on certain characteristics has
      been assumed to represent an effective strategy of implicit emotional regulation
      whereas processing based on simple perceptual characteristics (e.g., matching)
      has not. Evidence exists that the ventrolateral prefrontal cortex (VLPFC) might
      be of functional relevance during labeling by down-regulating limbic activity in
      the presence of threatening stimuli. However, it remained unclear whether this
      VLPFC activation was particularly specific to threat because previous studies
      focused exclusively on threatening stimuli. In the current study, 35 healthy
      participants labeled or matched both threatening and neutral pictures while
      undergoing 52-channel functional near-infrared spectroscopy. Results showed
      increased VLPFC activation during labeling of threatening but not neutral
      pictures. No increase in prefrontal activation was detected during matching.
      Moreover, skin conductance increased equally for both valence conditions during
      initial phases of labeling whereas during matching stronger increases were found
      for threatening stimuli. Although a general inverse relationship between VLPFC
      function and skin conductance was not confirmed, both were negatively correlated
      during matching of threatening pictures in subjects with high state anxiety. It
      was concluded that the VLPFC plays an essential role during implicit emotion
      regulation. Further, even simple perceptual processing seems to engage regulatory
      top-down activation in anxious individuals. 

PMID- 24096028
TI  - Switching auditory attention using spatial and non-spatial features recruits
      different cortical networks.
AB  - Switching attention between different stimuli of interest based on particular
      task demands is important in many everyday settings. In audition in particular,
      switching attention between different speakers of interest that are talking
      concurrently is often necessary for effective communication. Recently, it has
      been shown by multiple studies that auditory selective attention suppresses the
      representation of unwanted streams in auditory cortical areas in favor of the
      target stream of interest. However, the neural processing that guides this
      selective attention process is not well understood. Here we investigated the
      cortical mechanisms involved in switching attention based on two different types
      of auditory features. By combining magneto- and electro-encephalography (M-EEG)
      with an anatomical MRI constraint, we examined the cortical dynamics involved in
      switching auditory attention based on either spatial or pitch features. We
      designed a paradigm where listeners were cued in the beginning of each trial to
      switch or maintain attention halfway through the presentation of concurrent
      target and masker streams. By allowing listeners time to switch during a gap in
      the continuous target and masker stimuli, we were able to isolate the mechanisms
      involved in endogenous, top-down attention switching. Our results show a double
      dissociation between the involvement of right temporoparietal junction (RTPJ) and
      the left inferior parietal supramarginal part (LIPSP) in tasks requiring
      listeners to switch attention based on space and pitch features, respectively,
      suggesting that switching attention based on these features involves at least
      partially separate processes or behavioral strategies. 

PMID- 24096029
TI  - A T cell epitope-based vaccine protects against chlamydial infection in HLA-DR4
      transgenic mice.
AB  - Vaccination with recombinant chlamydial protease-like activity factor (rCPAF) has
      been shown to provide robust protection against genital Chlamydia infection.
      Adoptive transfer of IFN-gamma competent CPAF-specific CD4+ T cells was
      sufficient to induce early resolution of chlamydial infection and reduction of
      subsequent pathology in recipient IFN-gamma-deficient mice indicating the
      importance of IFN-gamma secreting CD4+ T cells in host defense against Chlamydia.
      In this study, we identify CD4+ T cell reactive CPAF epitopes and characterize
      the activation of epitope-specific CD4+ T cells following antigen immunization or
      Chlamydia challenge. Using the HLA-DR4 (HLA-DRB1*0401) transgenic mouse for
      screening overlapping peptides that induced T cell IFN-gamma production, we
      identified at least 5 CPAF T cell epitopes presented by the HLA-DR4 complex.
      Immunization of HLA-DR4 transgenic mice with a rCPAFep fusion protein containing
      these 5 epitopes induced a robust cell-mediated immune response and significantly
      accelerated the resolution of genital and pulmonary Chlamydia infection. rCPAFep
      vaccination induced CPAF-specific CD4+ T cells in the spleen were detected using
      HLA-DR4/CPAF-epitope tetramers. Additionally, CPAF-specific CD4+ clones could be
      detected in the mouse spleen following Chlamydia muridarum and a human Chlamydia
      trachomatis strain challenge using these novel tetramers. These results provide
      the first direct evidence that a novel CPAF epitope vaccine can provide
      protection and that HLA-DR4/CPAF-epitope tetramers can detect CPAF epitope
      specific CD4+ T cells in HLA-DR4 mice following C. muridarum or C. trachomatis
      infection. Such tetramers could be a useful tool for monitoring CD4+ T cells in
      immunity to Chlamydia infection and in developing epitope-based human vaccines
      using the murine model.

PMID- 24096030
TI  - Anti-leishmanial activity of the antimicrobial peptide DRS 01 observed in
      Leishmania infantum (syn. Leishmania chagasi) cells.
AB  - Leishmaniasis is one of the most serious diseases in the world and can be lethal
      if untreated. This is especially the case for visceral leishmaniasis, which is
      commonly caused by Leishmania (L.) infantum and for which available medication is
      still inadequate. A recently described antimicrobial peptide DRS 01 has been
      reported to kill L. infantum promastigotes, but nothing is known about its mode
      of action or effect on the cell. In this paper we report the visualization of the
      interaction between DRS 01 and L. infantum promastigotes using two high
      resolution microscopic techniques: atomic force microscopy and scanning electron
      microscopy. The results show considerable morphological changes at and above the
      IC50 in the treated cells. Both membrane damage and flagella alterations were
      observed. The results strongly suggest a membrane-directed action for DRS 01 on
      the Leishmania species studied. FROM THE CLINICAL EDITOR: In this paper, the
      effects of DRS 01, an antimicrobial peptide, is studied in Leishmania infantum
      using atomic force microscopy as well as standard scanning electron microscopy
      techniques, with the conclusion of a membrane-based effect by DRS 01 on the
      parasites.

PMID- 24096031
TI  - Novel thermosensitive hydrogels based on methoxy polyethylene glycol-co
      poly(lactic acid-co-aromatic anhydride) for cefazolin delivery.
AB  - Thermosensitive micelles composed of a copolymer of methoxy polyethylene glycol
      (mPEG), polylactic acid (PLA), and 1,6-bis (p-carboxyphenoxy) hexane (CPH),
      namely methoxy polyethylene glycol-co-polylactic acid-co-aromatic anhydride (mPEG
      PLCPHA), were fabricated for application as a promising hydrophilic drug carrier.
      The copolymer can self-assemble into micelles in PBS by hydrophobic interaction.
      The diameters of these micelles increased as the environmental temperature
      increased. An increase in viscosity with sol-to-gel transition occurred as
      temperature increased from room temperature to body temperature. During the in
      vitro degradation process, hydrogels demonstrated a more stable degradation rate.
      Both in vitro and in vivo cytotoxicity results showed that the materials had
      excellent biocompatibility due to less acidic products formation. In vitro
      cefazolin release profiles showed a stable release for 30 days. The hydrogel
      encapsulated cefazolin exhibited a good antibacterial effect. Based on these
      results, mPEG-PLCPHA can serve as an injectable depot gel for drug delivery. FROM
      THE CLINICAL EDITOR: In this study, thermosensitive hydrogel encapsulated
      cefazolin was found to exhibit good antibacterial effects with sustained levels
      for up to 30 days, enabling the development of an injectable depot gel for long
      term drug delivery.

PMID- 24096032
TI  - Theranostic immunoliposomes for osteoarthritis.
AB  - Although there have been substantial advancements in the treatment of
      inflammatory arthritis, treatments for osteoarthritis (OA) have lagged and
      currently are primarily palliative until joints become totally dysfunctional and
      prosthetic replacement is needed. One obstacle for developing a preventive
      therapy for OA is the lack of good tools for efficiently diagnosing the disease
      and monitoring its progression during the early stages when the effect of
      therapeutic drugs or biologics is most likely to be effective. We have developed
      near infrared immunoliposomes conjugated with type II collagen antibody for
      diagnosis and treatment of early OA. These immunoliposomes bind to damaged but
      not normal cartilage. Utilizing these reagents, we can quantitate exposure of
      type II collagen during cartilage degradation in individual joints in vivo in a
      guinea pig. Immunoliposomes could be used to determine the effectiveness of
      therapeutic interventions in small animals as well as vehicles for localized drug
      delivery to OA chondrocytes. FROM THE CLINICAL EDITOR: This team of authors have
      developed near infrared immunoliposomes conjugated with type II collagen antibody
      for diagnosis and treatment of early OA, with promising results demonstrated in a
      guinea pig model.

PMID- 24096033
TI  - Accelerated recovery of renal mitochondrial and tubule homeostasis with SIRT1/PGC
      1alpha activation following ischemia-reperfusion injury.
AB  - Kidney ischemia-reperfusion (I/R) injury elicits cellular injury in the proximal
      tubule, and mitochondrial dysfunction is a pathological consequence of I/R.
      Promoting mitochondrial biogenesis (MB) as a repair mechanism after injury may
      offer a unique strategy to restore both mitochondrial and organ function. Rats
      subjected to bilateral renal pedicle ligation for 22 min were treated once daily
      with the SIRT1 activator SRT1720 (5mg/kg) starting 24h after reperfusion until
      72h-144 h. SIRT1 expression was elevated in the renal cortex of rats after
      I/R+vehicle treatment (IRV), but was associated with less nuclear localization.
      SIRT1 expression was even further augmented and nuclear localization was restored
      in the kidneys of rats after I/R+SRT1720 treatment (IRS). PGC-1alpha was elevated
      at 72 h-144 h in IRV and IRS kidneys; however, SRT1720 treatment induced
      deacetylation of PGC-1alpha, a marker of activation. Mitochondrial proteins ATP
      synthase beta, COX I, and NDUFB8, as well as mitochondrial respiration, were
      diminished 24h-144 h in IRV rats, but were partially or fully restored in IRS
      rats. Urinary kidney injury molecule-1 (KIM-1) was persistently elevated in both
      IRV and IRS rats; however, KIM-1 tissue expression was attenuated in IRS rats.
      Additionally, sustained loss of Na(+),K(+)-ATPase expression and basolateral
      localization and elevated vimentin in IRV rats was normalized in IRS rats,
      suggesting restoration of a differentiated, polarized tubule epithelium. The
      results suggest that SRT1720 treatment expedited recovery of mitochondrial
      protein expression and function by enhancing MB, which was associated with faster
      proximal tubule repair. Targeting MB may offer unique therapeutic strategy
      following ischemic injury.

PMID- 24096034
TI  - Green tea polyphenol, (-)-epigallocatechin-3-gallate, induces toxicity in human
      skin cancer cells by targeting beta-catenin signaling.
AB  - The green tea polyphenol, (-)-epigallocatechin-3-gallate (EGCG), has been shown
      to have anti-carcinogenic effects in several skin tumor models, and efforts are
      continued to investigate the molecular targets responsible for its cytotoxic
      effects to cancer cells. Our recent observation that beta-catenin is upregulated
      in skin tumors suggested the possibility that the anti-skin carcinogenic effects
      of EGCG are mediated, at least in part, through its effects on beta-catenin
      signaling. We have found that treatment of the A431 and SCC13 human skin cancer
      cell lines with EGCG resulted in reduced cell viability and increased cell death
      and that these cytotoxic effects were associated with inactivation of beta
      catenin signaling. Evidence of EGCG-induced inactivation of beta-catenin
      included: (i) reduced accumulation of nuclear beta-catenin; (ii) enhanced levels
      of casein kinase1alpha, reduced phosphorylation of glycogen synthase kinase
      3beta, and increased phosphorylation of beta-catenin on critical serine(45,33/37)
      residues; and (iii) reduced levels of matrix metalloproteinase (MMP)-2 and MMP-9,
      which are down-stream targets of beta-catenin. Treatment of cells with
      prostaglandin E2 (PGE2) enhanced the accumulation of beta-catenin and enhanced
      beta-catenin signaling. Treatment with either EGCG or an EP2 antagonist (AH6809)
      reduced the PGE2-enhanced levels of cAMP, an upstream regulator of beta-catenin.
      Inactivation of beta-catenin by EGCG resulted in suppression of cell survival
      signaling proteins. siRNA knockdown of beta-catenin in A431 and SCC13 cells
      reduced cell viability. Collectively, these data suggest that induction of
      cytotoxicity in skin cancer cells by EGCG is mediated by targeting of beta
      catenin signaling and that the beta-catenin signaling is upregulated by
      inflammatory mediators. 

PMID- 24096035
TI  - Ascofuranone suppresses EGF-induced HIF-1alpha protein synthesis by inhibition of
      the Akt/mTOR/p70S6K pathway in MDA-MB-231 breast cancer cells.
AB  - Hypoxia-inducible factor (HIF)-1 plays an important role in tumor progression,
      angiogenesis and metastasis. In this study, we investigated the potential
      molecular mechanisms underlying the anti-angiogenic effect of ascofuranone, an
      isoprenoid antibiotic from Ascochyta viciae, in epidermal growth factor (EGF)-1
      responsive human breast cancer cells. Ascofuranone significantly and selectively
      suppressed EGF-induced HIF-1alpha protein accumulation, whereas it did not affect
      the expression of HIF-1beta. Furthermore, ascofuranone inhibited the
      transcriptional activation of vascular endothelial growth factor (VEGF) by
      reducing protein HIF-1alpha. Mechanistically, we found that the inhibitory
      effects of ascofuranone on HIF-1alpha protein expression are associated with the
      inhibition of synthesis HIF-1alpha through an EGF-dependent mechanism. In
      addition, ascofuranone suppressed EGF-induced phosphorylation of Akt/mTOR/p70S6
      kinase, but the phosphorylation of ERK/JNK/p38 kinase was not affected by
      ascofuranone. These results suggest that ascofuranone suppresses EGF-induced HIF
      1alpha protein translation through the inhibition of Akt/mTOR/p70S6 kinase
      signaling pathways and plays a novel role in the anti-angiogenic action. 

PMID- 24096037
TI  - o-p'-DDT-mediated uterotrophy and gene expression in immature C57BL/6 mice and
      Sprague-Dawley rats.
AB  - 1,1,1-Trichloro-2,2-bis(2-chlorophenyl-4-chlorophenyl)ethane (o,p'-DDT) is an
      organochlorine pesticide and endocrine disruptor known to activate the estrogen
      receptor. Comprehensive ligand- and species-comparative dose- and time-dependent
      studies were conducted to systematically assess the uterine physiological,
      morphological and gene expression responses elicited by o,p'-DDT and ethynyl
      estradiol (EE) in immature ovariectomized C57BL/6 mice and Sprague-Dawley rats.
      Custom cDNA microarrays were used to identify conserved and divergent
      differential gene expression responses. A total of 1256 genes were differentially
      expressed by both ligands in both species, 559 of which exhibited similar
      temporal expression profiles suggesting that o,p'-DDT elicits estrogenic effects
      at high doses when compared to EE. However, 51 genes exhibited species-specific
      uterine expression elicited by o,p'-DDT. For example, carbonic anhydrase 2
      exhibited species- and ligand-divergent expression as confirmed by quantitative
      real-time PCR. The identification of comparable temporal phenotypic responses
      linked to gene expression demonstrates that systematic comparative gene
      expression assessments are valuable for elucidating conserved and divergent
      estrogen signaling mechanisms in rodent uterotrophy. 

PMID- 24096036
TI  - Plasma biomarkers of liver injury and inflammation demonstrate a lack of
      apoptosis during obstructive cholestasis in mice.
AB  - Cholestasis is a pathological common component of numerous liver diseases that
      results in hepatotoxicity, inflammation, and cirrhosis when untreated. While the
      predominant hypothesis in cholestatic liver injury remains hepatocyte apoptosis
      due to direct toxicity of hydrophobic bile acid exposure, recent work suggests
      that the injury occurs through inflammatory necrosis. In order to resolve this
      controversy, we used novel plasma biomarkers to assess the mechanisms of cell
      death during early cholestatic liver injury. C57Bl/6 mice underwent bile duct
      ligation (BDL) for 6-72 h, or sham operation. Another group of mice were given d
      galactosamine and endotoxin as a positive control for apoptosis and inflammatory
      necrosis. Plasma levels of full length cytokeratin-18 (FL-K18), microRNA-122 (miR
      122) and high mobility group box-1 protein (HMGB1) increased progressively after
      BDL with peak levels observed after 48 h. These results indicate extensive cell
      necrosis after BDL, which is supported by the time course of plasma alanine
      aminotransferase activities and histology. In contrast, plasma caspase-3
      activity, cleaved caspase-3 protein and caspase-cleaved cytokeratin-18 fragments
      (cK18) were not elevated at any time during BDL suggesting the absence of
      apoptosis. In contrast, all plasma biomarkers of necrosis and apoptosis were
      elevated 6 h after Gal/End treatment. In addition, acetylated HMGB1, a marker for
      macrophage and monocyte activation, was increased as early as 12 h but mainly at
      48-72 h. However, progressive neutrophil accumulation in the area of necrosis
      started at 6h after BDL. In conclusion, these data indicate that early
      cholestatic liver injury in mice is an inflammatory event, and occurs through
      necrosis with little evidence for apoptosis.

PMID- 24096038
TI  - Physiology of reproductive senescence in Florida scrub-jays: results from a long
      term study and GnRH challenge.
AB  - In most vertebrates, production of reproductive hormones wanes with age, co
      occurring with a decline in reproductive output. Measurement of these hormones
      can serve as a key marker of the onset of reproductive senescence. Longitudinal
      studies of physiological parameters in populations of free-living animals are
      relatively uncommon; however, we have monitored baseline concentrations of
      hormones for nine years in a population of Florida scrub-jays (Aphelocoma
      coerulescens). We hypothesized that concentrations of circulating reproductive
      hormones change with age, and predicted declines in reproductive hormones in the
      oldest jays. We found that baseline levels of luteinizing hormone (LH) and
      testosterone (T) were relatively low in both young and old male breeders and
      reach their highest levels in birds aged 4-7years. Conversely, we found no age
      related patterns in baseline levels of LH or estradiol in female jays. In males
      we determined which component of the hypothalamo-pituitary-gonadal (HPG) axis is
      responsible for observed age-based differences, by challenging males of different
      ages with gonadotropin-releasing hormone (GnRH); thereby allowing assessment of
      pituitary and gonadal responsiveness by measuring plasma concentrations of
      luteinizing hormone and testosterone, respectively. The magnitude of increase in
      levels of both LH and T in response to GnRH challenge decreased with age in male
      breeders. Combined with the baseline levels, the results from the GnRH challenge
      suggest that younger birds have the capability to produce higher levels of
      reproductive hormone, whereas the old birds may be constrained by senescence in
      their ability to produce these hormones. 

PMID- 24096039
TI  - Modelling future impacts of air pollution using the multi-scale UK Integrated
      Assessment Model (UKIAM).
AB  - Integrated assessment modelling has evolved to support policy development in
      relation to air pollutants and greenhouse gases by providing integrated
      simulation tools able to produce quick and realistic representations of emission
      scenarios and their environmental impacts without the need to re-run complex
      atmospheric dispersion models. The UK Integrated Assessment Model (UKIAM) has
      been developed to investigate strategies for reducing UK emissions by bringing
      together information on projected UK emissions of SO2, NOx, NH3, PM10 and PM2.5,
      atmospheric dispersion, criteria for protection of ecosystems, urban air quality
      and human health, and data on potential abatement measures to reduce emissions,
      which may subsequently be linked to associated analyses of costs and benefits. We
      describe the multi-scale model structure ranging from continental to roadside, UK
      emission sources, atmospheric dispersion of emissions, implementation of
      abatement measures, integration with European-scale modelling, and environmental
      impacts. The model generates outputs from a national perspective which are used
      to evaluate alternative strategies in relation to emissions, deposition patterns,
      air quality metrics and ecosystem critical load exceedance. We present a
      selection of scenarios in relation to the 2020 Business-As-Usual projections and
      identify potential further reductions beyond those currently being planned. 

PMID- 24096040
TI  - Health burdens of surface ozone in the UK for a range of future scenarios.
AB  - Exposure to surface ozone (O3), which is influenced by emissions of precursor
      chemical species, meteorology and population distribution, is associated with
      excess mortality and respiratory morbidity. In this study, the EMEP-WRF
      atmospheric chemistry transport model was used to simulate surface O3
      concentrations at 5km horizontal resolution over the British Isles for a baseline
      year of 2003, for three anthropogenic emissions scenarios for 2030, and for a +5
      degrees C increase in air temperature on the 2003 baseline. Deaths brought
      forward and hospitalisation burdens for 12 UK regions were calculated from
      population-weighted daily maximum 8-hour O3. The magnitude of changes in annual
      mean surface O3 over the UK for +5 degrees C temperature (+1.0 to +1.5ppbv,
      depending on region) was comparable to those due to inter-annual meteorological
      variability (-1.5 to +1.5ppbv) but considerably less than changes due to
      precursor emissions changes by 2030 (-3.0 to +3.5ppbv, depending on scenario and
      region). Including population changes in 2030, both the 'current legislation' and
      'maximum feasible reduction' scenarios yield greater O3-attributable health
      burdens than the 'high' emission scenario: +28%, +22%, and +16%, respectively,
      above 2003 baseline deaths brought forward (11,500) and respiratory hospital
      admissions (30,700), using O3 exposure over the full year and no threshold for
      health effects. The health burdens are greatest under the 'current legislation'
      scenario because O3 concentrations increase as a result of both increases in
      background O3 concentration and decreases in UK NOx emissions. For the +5 degrees
      C scenario, and no threshold (and not including population increases), total UK
      health burden increases by 500 premature deaths (4%) relative to the 2003
      baseline. If a 35ppbv threshold for O3 effects is assumed, health burdens are
      more sensitive to the current legislation and +5 degrees C scenarios, although
      total health burdens are roughly an order of magnitude lower. In all scenarios,
      the assumption of a threshold increases the proportion of health burden in the
      south and east of the UK compared with the no threshold assumption. The study
      highlights that the total, and geographically-apportioned, O3-attributable health
      burdens in the UK are highly sensitive to the future trends of hemispheric,
      regional and local emissions of O3 precursors, and to the assumption of a
      threshold for O3 effect. 

PMID- 24096041
TI  - Potential water saving through changes in European diets.
AB  - This study quantifies the water footprint of consumption (WFcons) regarding
      agricultural products for three diets - the current diet (REF), a healthy diet
      (HEALTHY) and a vegetarian diet (VEG) - for the four EU zones WEST, NORTH, SOUTH
      and EAST. The WFcons related to the consumption of agricultural products (4265l
      per capita per day or lcd) accounts for 89% of the EU's total WFcons (4815lcd).
      The effect of diet has therefore an essential impact on the total WFcons. The
      current zonal WFcons regarding agricultural products is: 5875lcd (SOUTH), 4053lcd
      (EAST), 3761lcd (WEST) and 3197lcd (NORTH). These differences are the result of
      different consumption behaviours as well as different agricultural production
      methods and conditions. From the perspective of a healthy diet based on regional
      dietary guidelines, the intake of several product groups (sugar, crop oils,
      animal fats and meat) should be decreased and increased for others (vegetables,
      fruit). The WFcons regarding agricultural products for the alternative diets are
      the following: HEALTHY 4110lcd (-30%) and VEG 3476lcd (-41%) for SOUTH; HEALTHY
      3606lcd (-11%) and VEG 2956lcd (-27%) for EAST; HEALTHY 2766lcd (-26%) and VEG
      2208lcd (-41%) for WEST; HEALTHY 3091lcd (-3%) and VEG 2166lcd (-32%) for NORTH.
      Both the healthy and vegetarian diets thus result - consistent for all zones - in
      substantial WFcons reductions. The largest reduction takes place for the
      vegetarian diet. Indeed, a lot of water can be saved by EU citizens by a change
      in their diet. 

PMID- 24096042
TI  - Pyrethroids in house dust from the homes of farm worker families in the MICASA
      study.
AB  - Indoor pesticide exposure is a growing concern, particularly for pyrethroids, a
      commonly used class of pesticides. Pyrethroid concentrations may be especially
      high in homes of immigrant farm worker families, who often live in close
      proximity to agricultural fields and are faced with poor housing conditions,
      potentially causing high pest infestation and pesticide use. We investigate
      levels of pyrethroids in the house dust of farm worker family homes in a study of
      mothers and children living in Mendota, CA, within the population-based Mexican
      Immigration to California: Agricultural Safety and Acculturation (MICASA) Study.
      We present pesticide use data and levels of pyrethroid pesticides in indoor dust
      collected in 2009 as measured by questionnaires and a GC/MS analysis of the
      pyrethroids cis- and trans-permethrin, cypermethrin, deltamethrin, esfenvalerate
      and resmethrin in single dust samples collected from 55 households. Cis- and
      trans-permethrin had the highest detection frequencies at 67%, with median
      concentrations of 244 and 172ng/g dust, respectively. Cypermethrin was detected
      in 52% of the homes and had a median concentration of 186ng/g dust.
      Esfenvalerate, resmethrin and deltamethrin were detected in less than half the
      samples. We compared the pyrethroid concentrations found in our study to other
      studies looking at both rural and urban homes and daycares. Lower detection
      frequencies and/or lower median concentrations of cis- and trans-permethrin and
      cypermethrin were observed in our study as compared to those studies. However,
      deltamethrin, esfenvalerate and resmethrin were detected more frequently in the
      house dust from our study than in the other studies. Because households whose
      children had higher urinary pyrethroid metabolite levels were more likely to be
      analyzed in this study, a positive bias in our estimates of household pyrethroid
      levels may be expected. A positive association was observed with reported outdoor
      pesticide use and cypermethrin levels found in the indoor dust samples (rs=0.28,
      p=0.0450). There was also a positive association seen with summed pyrethroid
      levels in house dust and the results of a pesticide inventory conducted by field
      staff (rs=0.32, p=0.018), a potentially useful predictor of pesticide exposure in
      farm worker family homes. Further research is warranted to fully investigate the
      utility of such a measure. 

PMID- 24096043
TI  - Effect of increasing depth of dexmedetomidine and propofol anesthesia on upper
      airway morphology in children and adolescents with obstructive sleep apnea.
AB  - STUDY OBJECTIVE: To examine the dose-response effects of dexmedetomidine (DEX)
      and propofol (PROP) on airway morphology in children and adolescents with a
      history of obstructive sleep apnea (OSA). DESIGN: Prospective, single-blinded,
      controlled comparative study. SETTING: University-affiliated teaching hospital.
      PATIENTS: 60 patients with a history of OSA who presented for a magnetic
      resonance imaging (MRI) sleep study. INTERVENTIONS: Patients were randomized to
      two equal groups (DEX or PROP). Magnetic resonance images of the airway were
      obtained during low (1 MUg/kg/hr) and high (3 MUg/kg/hr) doses of DEX, or low
      (100 MUg/kg/m) and high (200 MUg/kg/m) doses of PROP, based on group assignment.
      MEASUREMENTS: The airway anteroposterior (AP) diameter, transverse diameter, and
      sectional areas were measured at the level of the nasopharyngeal airway and
      retroglossal airway. The influence of the two drugs and OSA severity, as
      determined by polysomnography, on airway dimensions was examined using mixed
      effects analysis of covariance models. MAIN RESULTS: Upper airway morphology was
      completed in 45 patients. Most airway measurements showed statistically
      nonsignificant associations with increasing doses of PROP and DEX. As the dosage
      increased, average airway dimensions were typically unchanged or slightly
      increased with DEX compared with airway dimensions that were unchanged or
      slightly decreased with PROP. An airway intervention was required in three
      children (11%) in the DEX group and 7 children (23%) in the PROP group (P = NS).
      CONCLUSIONS: Both agents provided an acceptable level of anesthesia for MRI sleep
      studies in patients with OSA, with statistically nonsignificant changes in airway
      dimensions.

PMID- 24096044
TI  - Estrogen associated gene polymorphisms and their interactions in the progress of
      Alzheimer's disease.
AB  - The extensive neuroprotective effects of estrogen against Alzheimer's disease
      (AD) have been proven in numerous laboratory studies. However, in clinical
      studies, the exact role of estrogen in AD is still ambiguous. Some evidences even
      suggested the high levels of estrogen or estrogen replacement treatment increased
      the risk of AD. Thus, there must be other factors affecting the neuroprotective
      effects of estrogen. Multiple enzymes and receptor proteins are involved in the
      biosynthesis, metabolism and signaling pathways of estrogen, and mediate the
      beneficial effects of estrogen on AD. Previous studies have suggested some
      polymorphisms of genes encoding these enzymes and proteins are associated with
      the risk of AD. In addition to the genes associated with estrogen biosynthesis
      and metabolism and the genes encoding estrogen receptor proteins, some other
      genes also modulate the effects of estrogen on AD, or interact with other
      estrogen-associated genes on the progress of AD. The gene-hormone and gene-gene
      interactions may be key to unraveling the conflicting results regarding the
      effect of estrogen on AD. In this paper, we will review and discuss the
      associations between polymorphisms of these genes and their interactions and the
      susceptibility to AD. A better understanding of these estrogen-associated genes
      is significant to explore the pathogenesis of AD. 

PMID- 24096045
TI  - Effect of pharmacological enhancement on cognitive and clinical psychomotor
      performance of sleep-deprived doctors.

PMID- 24096046
TI  - Advantages of the experimental animal hollow organ mechanical testing system for
      the rat colon rupture pressure test.
AB  - BACKGROUND: Many studies have been conducted on colorectal anastomotic leakage to
      reduce the incidence of anastomotic leakage. However, how to precisely determine
      if the bowel can withstand the pressure of a colorectal anastomosis experiment,
      which is called anastomotic bursting pressure, has not been determined. METHOD: A
      task force developed the experimental animal hollow organ mechanical testing
      system to provide precise measurement of the maximum pressure that an anastomotic
      colon can withstand, and to compare it with the commonly used method such as the
      mercury and air bag pressure manometer in a rat colon rupture pressure test.
      Forty-five male Sprague-Dawley rats were randomly divided into the manual ball
      manometry (H) group, the tracing machine manometry pressure gauge head (MP)
      group, and the experimental animal hollow organ mechanical testing system (ME)
      group. The rats in each group were subjected to a cut colon rupture pressure test
      after injecting anesthesia in the tail vein. Colonic end-to-end anastomosis was
      performed, and the rats were rested for 1 week before anastomotic bursting
      pressure was determined by one of the three methods. RESULTS: No differences were
      observed between the normal colon rupture pressure and colonic anastomotic
      bursting pressure, which were determined using the three manometry methods.
      However, several advantages, such as reduction in errors, were identified in the
      ME group. CONCLUSION: Different types of manometry methods can be applied to the
      normal rat colon, but the colonic anastomotic bursting pressure test using the
      experimental animal hollow organ mechanical testing system is superior to
      traditional methods.

PMID- 24096047
TI  - From the CUPIC study: great times are not coming (?).

PMID- 24096048
TI  - Liver fibrosis progression at autopsy in injecting drug users infected by
      hepatitis C: a longitudinal long-term cohort study.
AB  - BACKGROUND & AIMS: There is a paucity of unbiased data on the natural history of
      hepatitis C virus (HCV) infection in injecting drug users (IDUs). The purpose of
      this study was to assess the risk of developing advanced fibrosis associated with
      chronic hepatitis C (CHC) infection among injecting drug users (IDUs) who
      underwent an autopsy. METHODS: A longitudinal cohort design was applied, in which
      the stage of liver fibrosis in anti-HCV positive IDUs with or without chronic HCV
      infection was assessed in liver tissue from autopsies performed up to 35 years
      after HCV exposure. The cohort originated from 864 IDUs consecutively admitted
      for drug abuse treatment 1970-1984. Stored sera, mostly drawn at the time of
      admission for drug treatment, were available in 635 subjects. 220 out of 523 anti
      HCV positive subjects had died before 2009. Liver tissue from autopsies was
      available from 102/220 subjects, of which 61 were HCV RNA positive. Liver
      sections were classified according to METAVIR scores for fibrosis. Two
      pathologists, both blinded for serologic results, scored sections of liver
      tissue. RESULTS: Among HCV RNA positive subjects 16.4% (10/61) had septal
      fibrosis (F3) or cirrhosis (F4) compared to 2.4% (1/41) among anti HCV
      positive/HCV RNA negative subjects (p=0.026). Of 18 HCV RNA positive subjects
      autopsied <15 years after HCV exposure none had F3 or F4. Among subjects
      autopsied >25 years after exposure 35% (6/17) had F3-F4. CONCLUSIONS: Among IDUs
      chronically infected by HCV, 1/3 developed septal fibrosis or cirrhosis 25 years
      or more after exposure.

PMID- 24096049
TI  - High hepatitis B virus surface antigen levels and favorable interleukin 28B
      genotype predict spontaneous hepatitis C virus clearance in uremic patients.
AB  - BACKGROUND & AIMS: Host and viral factors interplay in the spontaneous clearance
      of hepatitis C virus (HCV) infection. We aimed to explore the roles of IL28B
      genotypes and hepatitis B virus (HBV) infections in spontaneous HCV
      seroclearance. METHODS: IL28B rs8099917 genotypes, HCV and HBV markers were
      determined in 290 patients who were seropositive for HCV antibodies from 1681
      total uremic patients on maintenance hemodialysis. RESULTS: Persistent HCV
      viremia was observed in 74.6% (214/287) of patients. Logistic regression revealed
      that the strongest factors associated with spontaneous HCV seroclearance were
      carriage of rs8099917 TT-type (odds ratio/95% confidence intervals [OR/CI]:
      6.22/1.41-27.35, p=0.016), followed by concurrent hepatitis B surface antigen
      (HBsAg) seropositivity (OR/CI: 2.37/1.06-5.26, p=0.035). The clearance rate was
      highest among patients with both positive HBsAg/rs8099917 TT-type (44.8%, OR/CI:
      20.88/3.5-402.5), followed by positive HBsAg/rs8099917 non-TT-type (28.6%, OR/CI:
      8.86/1.8-160.8), and negative HBsAg/rs8099917 TT-type (26.7%, OR/CI: 12.75/1.0
      319.4), compared to 4% of negative HBsAg/rs8099917 non-TT-type (trend p=0.0002).
      HBsAg levels, but not HBV DNA levels, were significantly associated with
      spontaneous HCV seroclearance. Spontaneous HCV seroclearance rate was 58.3% in
      patients with HBsAg>200IU/ml/rs8099917 TT-type (OR/CI: 42.54/5.7-908.4), 28.0% in
      patients with HBsAg<200IU/ml/rs8099917 TT-type or HBsAg>200IU/ml/rs8099917 non-TT
      type (OR/CI: 11.12/2.3-201.0), compared to only 3.3% in those with
      HBsAg<200IU/ml/rs8099917 non-TT-type (trend p=0.0004). Five of 214 (2.3%) HCV
      viremic patients at enrollment had spontaneous HCV seroclearance during one-year
      follow-up, which was associated with baseline HCV RNA and HBsAg levels.
      CONCLUSIONS: High HBsAg levels and favorable IL28B genotype were additively
      associated with spontaneous HCV seroclearance in uremic patients.

PMID- 24096050
TI  - Perforin and granzymes work in synergy to mediate cholangiocyte injury in
      experimental biliary atresia.
AB  - BACKGROUND & AIMS: Biliary atresia represents obstructive cholangiopathy in
      infants progressing rapidly to cirrhosis and end-stage liver disease. Activated
      NK cells expressing Nkg2d have been linked to bile duct injury and obstruction by
      establishing contact with cholangiocytes. To define the mechanisms used by
      cytotoxic cells, we investigated the role of perforin and granzymes in a neonatal
      mouse model of rotavirus (RRV)-induced biliary atresia. METHODS: We used
      complementary cell lysis assays, flow cytometric analyses, quantitative PCRs and
      in vivo systems to determine the mechanisms of bile duct epithelial injury and
      the control of the tissue phenotype in experimental biliary atresia. RESULTS: RRV
      infected hepatic NK and CD8 T cells increased the expression of perforin and
      injured cholangiocytes in short-term culture in a perforin-dependent fashion.
      However, the loss of perforin in vivo delayed but did not prevent the obstruction
      of bile ducts. Based on the increased expression of granzymes by perforin
      deficient cytotoxic cells in long-term cytolytic assays, we found that the
      inhibition of granzymes by nafamostat mesilate (FUT-175) blocked cholangiocyte
      lysis. Administration of FUT-175 to perforin-deficient mice after RRV infection
      decreased the development of jaundice, minimized epithelial injury, and improved
      long-term survival. However, the inhibition of granzymes alone in wild-type mice
      was not sufficient to prevent the atresia phenotype in newborn mice. In infants
      with biliary atresia, hepatic Granzymes A and B mRNA, but not Perforin, increased
      at the time of portoenterostomy. CONCLUSIONS: Perforin and granzymes have
      complementary roles mediating epithelial injury by NK and CD8 T cells. The
      prevention of experimental biliary atresia can only be achieved by inhibiting
      both granules.

PMID- 24096051
TI  - Role of Myc in hepatocellular proliferation and hepatocarcinogenesis.
AB  - BACKGROUND & AIMS: Myc is involved in cell growth, proliferation, apoptosis,
      energy metabolism, and differentiation. Whether it is essential for
      hepatocellular proliferation and carcinogenesis is unclear due to a lack of an
      efficient hepatocyte-specific Myc disruption model. This study used a novel
      genetic model to investigate the involvement of Myc in hepatocellular
      proliferation and hepatocarcinogenesis in mice. METHODS: Temporal hepatocyte
      specific Myc disruption was achieved by use of the tamoxifen-inducible Cre-ER(T2)
      recombinase system under control of the serum albumin promoter. Hepatocyte
      proliferation was assessed by administering peroxisome proliferator-activated
      receptor alpha (PPARalpha) agonist Wy-14,643. A diethylnitrosamine-induced liver
      cancer model was used to evaluate the role of Myc in hepatocarcinogenesis.
      RESULTS: Tamoxifen administration induced recombination of Myc specifically in
      hepatocytes of Myc(fl/fl,ERT2-Cre) mice. When treated with a known hepatocellular
      proliferative stimulus Wy-14,643, Myc(fl/fl,ERT2-Cre) mice showed a lower
      liver/body weight ratio and suppressed hepatocyte proliferation as compared to
      Myc(fl/fl) mice. Hepatic expression of cell cycle control genes, DNA repair
      genes, and Myc target gene miRNAs were upregulated in Wy-14,643-treated
      Myc(fl/fl) mouse livers, but not in Wy-14,643-treated Myc(fl/fl,ERT2-Cre) livers.
      However, no differences were observed in the lipid-lowering effect of Wy-14,643
      between Myc(fl/fl,ERT2-Cre) and Myc(fl/fl) mice, consistent with no differences
      in the expression of several PPARalpha target genes involved in fatty acid beta
      oxidation. Moreover, when subjected to the diethylnitrosamine liver cancer
      bioassay, Myc(fl/fl,ERT2-Cre) mice exhibited a markedly lower incidence of tumor
      formation compared with Myc(fl/fl) mice. CONCLUSIONS: Myc plays an essential role
      in hepatocellular proliferation and liver tumorigenesis.

PMID- 24096052
TI  - RIPiT-Seq: a high-throughput approach for footprinting RNA:protein complexes.
AB  - Development of high-throughput approaches to map the RNA interaction sites of
      individual RNA binding proteins (RBPs) transcriptome-wide is rapidly transforming
      our understanding of post-transcriptional gene regulatory mechanisms. Here we
      describe a ribonucleoprotein (RNP) footprinting approach we recently developed
      for identifying occupancy sites of both individual RBPs and multi-subunit RNP
      complexes. RNA:protein immunoprecipitation in tandem (RIPiT) yields highly
      specific RNA footprints of cellular RNPs isolated via two sequential
      purifications; the resulting RNA footprints can then be identified by high
      throughput sequencing (Seq). RIPiT-Seq is broadly applicable to all RBPs
      regardless of their RNA binding mode and thus provides a means to map the RNA
      binding sites of RBPs with poor inherent ultraviolet (UV) crosslinkability.
      Further, among current high-throughput approaches, RIPiT has the unique capacity
      to differentiate binding sites of RNPs with overlapping protein composition. It
      is therefore particularly suited for studying dynamic RNP assemblages whose
      composition evolves as gene expression proceeds. 

PMID- 24096053
TI  - BDNF, interleukin-6, and salivary cortisol levels in depressed patients treated
      with desvenlafaxine.
AB  - BACKGROUND: Relationships between brain-derived neurotrophic factor (BDNF),
      interleukin (IL)-6, and salivary cortisol and both depression severity and
      treatment response were assessed in patients enrolled in a double-blind, placebo
      controlled trial of desvenlafaxine 50mg/d for MDD. METHODS: Outpatients with MDD
      were randomly assigned to 12weeks of double-blind treatment with desvenlafaxine
      50mg/d or placebo (2:1). Baseline severity was assessed using the 17-item
      Hamilton Rating Scale for Depression (HAM-D17); treatment response at week 12 was
      based on HAM-D17 total score and response and remission status. Saliva (cortisol)
      and blood (BDNF, IL-6) samples for biomarker assay were collected at baseline and
      week 12. Spearman correlations were calculated between the biomarkers at
      baseline, and between biomarkers and HAM-D17 total score at baseline. Logistic
      regression analyses were used to assess whether baseline biomarker levels
      predicted treatment response at week 12, with and without adjustment for baseline
      HAM-D17 score, treatment, and geographic region. Similarly, an analysis of
      covariance was used to assess whether baseline disease severity predicted
      biomarker change at week 12. RESULTS: A total of 427 patients who received >=1
      dose of study drug and had baseline and >=1 on-therapy primary efficacy
      evaluations were included in the analysis. At baseline, there was a statistically
      significant although weak correlation between levels of IL-6 and BDNF (Spearman
      correlation coefficient [rs]=0.120; P=0.014), but no significant correlation
      between baseline biomarker levels and baseline HAM-D17 total score (absolute
      value of all rs, <=0.061). Desvenlafaxine 50mg/d treatment significantly reduced
      HAM-D17 total score from baseline at week 12 compared with placebo (P=0.006), but
      the three potential biomarkers did not predict treatment effects. No significant
      correlations were observed between the change from baseline in any biomarker
      level and change in HAM-D17 total score at week 12, either overall, or in
      desvenlafaxine or placebo groups (absolute value of all rs, 0.003-0.196).
      Baseline levels of BDNF, IL-6, and salivary cortisol did not significantly
      predict response to treatment at week 12. Although median increase in BDNF was
      not significantly different between desvenlafaxine (13.7%) and placebo (5.7%)
      groups, the increase was significantly greater (33.4% vs 4.3%; P=0.003) in
      patients with more severe depression at baseline (HAM-D17>22) vs those with less
      severe depression (HAM-D17<=22). No similar findings were observed for IL-6 or
      salivary cortisol. DISCUSSION: Weak or no relationships were observed at baseline
      between the potential biomarkers or between biomarkers and disease severity.
      While baseline biomarker level did not predict treatment response, improvement in
      BDNF was significantly greater among patients who were more severely depressed at
      baseline.

PMID- 24096054
TI  - Substantial incongruence among the morphology, taxonomy, and molecular phylogeny
      of the land snails Aegista, Landouria, Trishoplita, and Pseudobuliminus
      (Pulmonata: Bradybaenidae) occurring in East Asia.
AB  - Analyses of molecular phylogeny have revealed that phenotypically identified taxa
      do not reflect phylogenetic relationships. Such taxa often are not evolutionary
      significant and are misleading in describing and evaluating biological diversity.
      Herein, we investigated the molecular phylogeny of the East Asian bradybaenid
      land snail genera Aegista, Landouria, Trishoplita, and Pseudobuliminus to test
      whether morphology and current taxonomy reflect phylogenetic relationships. Our
      results document extensive parallel evolution and substantial incongruence
      between taxonomy and molecular phylogeny. Species with an elongated turret shell
      evolved independently five times, and hair-like ornamentation of the shell was
      independently gained or lost in a number of lineages. Although genital anatomy
      reveals phylogenetic conservatism to some extent, love dart and dart-related
      organs were lost independently at least three times in these genera. Accordingly,
      classification of these genera based on morphological traits did not reflect
      phylogenetic relationships, and, overall, these genera except for a few species
      should be tentatively assigned to a single genus as Aegista. The present findings
      suggest that radical revision is required for the taxonomy of bradybaenid land
      snails. 

PMID- 24096055
TI  - Diversification of Scrophularia (Scrophulariaceae) in the Western Mediterranean
      and Macaronesia--phylogenetic relationships, reticulate evolution and
      biogeographic patterns.
AB  - The flora of the Mediterranean region and Macaronesia is characterized by high
      levels of species diversity and endemism. We examined phylogenetic relationships
      of Scrophularia within one of its secondary centers of diversity located in the
      Iberian Peninsula and adjacent Macaronesia. In total, 65 ingroup accessions from
      45 species, representing an almost complete sampling of the region, were analyzed
      using sequences from the internal transcribed spacer region (ITS) and the plastid
      trnQ-rps16 intergenic spacer. Phylogenetic relationships were inferred using
      Bayesian inference, maximum likelihood and statistical parsimony networking.
      Incongruence between datasets was assessed with statistical tests and displayed
      by split networks. Biogeographic inferences incorporating information from both
      markers (despite low resolution in some parts of the trees) and all incongruent
      taxa were accomplished with a novel combination of methods, using trees generated
      with the taxon duplication approach as input for Bayesian binary MCMC (BBM)
      analysis as implemented in RASP. Nuclear and chloroplast markers support a clade
      which comprises the majority of Iberian and Macaronesian species and consists of
      three subclades. Analyses of the substantial incongruence observed among markers
      indicate reticulate evolution and suggest that Scrophularia species diversity in
      this region is largely attributable to hybridization; a combination of both
      polyploidy and dysploidy in the karyotypic evolution of Western Mediterranean
      Scrophularia taxa is proposed. Our results provide support for an ancient
      hybridization event between two widespread lineages, which resulted in an
      allopolyploid ancestor of the Iberian - Macaronesian group with 2n=58
      chromosomes. The ancestor then diverged into the three main lineages present in
      the Iberian Peninsula, Northern Africa and Macaronesia today. Subsequent
      interspecific hybridizations at different ploidy levels additionally generated
      new species. Presumably, hybridization and diversification within the genus in
      the Western Mediterranean have not been restricted to one particular event, but
      occurred repeatedly. It can be assumed that the topographical complexity found in
      the Iberian Peninsula has promoted diversification and hybrid speciation
      processes in Scrophularia, and that isolation in glacial refugia has preserved
      recent and ancient lineages. For the Macaronesian taxa, biogeographic analyses
      support several origins, by colonizations from at least four distinct lineages. 

PMID- 24096056
TI  - Phylogenetic relationships of North American western chubs of the genus Gila
      (Cyprinidae, Teleostei), with emphasis on southern species.
AB  - Species of Gila comprise a heterogeneous and widespread group of freshwater
      fishes inhabiting drainage systems of western North America. The classification
      of species of Gila and relatives has been complicated and sometimes compromised
      by differences in body shapes, sizes, habitats, variable taxonomic placement by
      early taxonomists, and instances of hypothesized hybridization. While most
      attention on Gila has focused on hybridization in USA, little is actually know
      about their intra and intergeneric relationships. We present a molecular
      phylogeny using 173 specimens for all 19 recognized species of Gila, covering
      their entire distributions in 31 major drainages. Using one mitochondrial and
      three nuclear genes, specimens of Gila were analyzed with 10 other North American
      genera that comprise the Revised Western Clade. All analyses identified most
      species of Gila in a lineage that always included the monotypic genera Moapa and
      Acrocheilus, and we recommend the synonymy of both genera with Gila. The
      composition of this Gila lineage varied depending on the genes analyzed. Within
      the Gila lineage, similar morphotypes (forms adapted to fast currents vs. general
      forms) were not resolved as closest relatives. Analyses of mitochondrial DNA
      resolved all species of Gila from Mexico in reciprocally monophyletic clades
      except G. modesta. Most species of Gila in the USA were nested in 3 major clades,
      potentially indicating some level of historic or contemporary interspecific
      hybridization. Herein, we redefine the ranges for all species of Gila in Mexico.
      Relevant taxonomic and conservation implications stemming from the results are
      discussed. 

PMID- 24096057
TI  - Miocene-Pliocene speciation, introgression, and migration of Patis and
      Ptilagrostis (Poaceae: Stipeae).
AB  - Genetic interchange between American and Eurasian species is fundamental to our
      understanding of the biogeographical patterns, and we make a first attempt to
      reconstruct the evolutionary events in East Asia that lead to the origin and
      dispersal of two genera, Patis and Ptilagrostis. We conducted a molecular
      phylogenetic study of 78 species in the tribe Stipeae using four plastid DNA
      sequences (ndhF, rpl32-trnL, rps16-trnK, and rps16 intron) and two nuclear DNA
      sequences (ITS and At103). We use single copy nDNA gene At103 for the first time
      in the grasses to elucidate the evolutionary history among members of the
      Stipeae. Ampelodesmos, Hesperostipa, Oryzopsis, Pappostipa, Patis, and Stipa are
      found to be of multiple origins. Our phylograms reveal conflicting positions for
      Ptilagrostis alpina and Pt. porteri that form a clade with Patis coreana, P.
      obtusa, and P. racemosa in the combined plastid tree but are aligned with other
      members of Ptilagrostis in the ITS tree. We hypothesize that Ptilagrostis still
      retains the nucleotype of an extinct genus which transited the Bering land bridge
      from American origins in the late Miocene (minimum 7.35-6.37 mya) followed by
      hybridization and two plastid capture events with a Trikeraia-like taxon (7.96
      mya) and para-Patis (between 5.32 and 3.76 mya). Ptilagrostis porteri and Patis
      racemosa then migrated to continental North America 1.7-2.9 mya and 4.3-5.3 mya,
      respectively.

PMID- 24096058
TI  - Synthesis and characterization of 1,2-bis(2-(5-bromo-2-hydroxybenzilidenamino)-4
      chlorophenoxy)ethane and its metal complexes: an experimental, theoretical,
      electrochemical, antioxidant and antibacterial study.
AB  - A new Schiff base ligand was synthesized by reaction of 5-bromosalicylaldehyde
      with 1,2-bis(4-chloro-2-aminophenoxy)ethane. Then the Schiff base complexes were
      synthesized by the reaction of metal salts and the novel Schiff base. The molar
      conductivity properties of the complexes were studied and found out that the
      complexes are nonelectrolytes. The structures of the ligand and its metal
      complexes were characterized by elemental analysis, FT-IR, UV-VIS, magnetic
      susceptibility measurements, molar conductivity measurements, and thermal
      gravimetric analysis. In addition antioxidant, theoretical NMR studies and cyclic
      voltammetry of the complexes were done. Two methods namely metal chelating
      activity and diphenylpicrylhydrazyl (DPPH) radical scavenging method were used to
      determine the antioxidant activity, and antibacterial properties of the compounds
      were also studied. 

PMID- 24096059
TI  - Infrared characterization and electrochemical study of gamma
      methacryloxypropyltrimethoxysilane grafted in to surface of copper.
AB  - The formation of a protective layer of gamma-methacryloxypropyltrimethoxysilane
      (gamma-MPS) on copper is studied by diffuse reflectance infrared spectroscopy
      (DRIFT), gravimetric chemical (weight loss) and electrochemical (cyclic
      voltammetry and potentiodynamic polarization) measurements. By simple immersion
      in the silanic bath (90/5/5 v/v ethanol/water/silane), this agent immediately
      physisorbed on copper, but the protective effects are poor. Thiolate and siloxane
      band formation improve the performances of the silanic layer on the surface of
      copper especially after heat treatment process. Chemical and electrochemical
      measurements show that the protective action of heat treatment (HT/Cu-MPS)
      process is higher than that of aged process (aged/Cu-MPS).

PMID- 24096060
TI  - Linear and nonlinear optical studies of bare and copper doped TiO2 nanoparticles
      via sol gel technique.
AB  - In general, the nanoparticles of TiO2 may exist in the phases of anatase, rutile
      and brookite. In the present work, we used titanium terta iso propoxide and 2
      propanol as a common starting material to prepare the precursors of bare and
      copper doped nanosized TiO2. Then the synthesized products were calcinated at 500
      degrees C and after calcination the pure TiO2 nanoparticles in anatase phase were
      harvested. The crystallite sizes of bare and copper doped TiO2 nanoparticles were
      calculated from X-ray diffraction analysis. The existence of functional groups of
      the samples was identified by Fourier transform infrared spectroscopy. The
      optical properties of bare and doped samples were carried out using UV-DRS and
      photoluminescence measurements. The surface morphology and the element
      constitution of the copper doped TiO2 nanoparticles were studied by scanning
      electron microscope fitted with energy dispersive X-ray spectrometer arrangement.
      The nonlinear optical properties of the products were confirmed by Kurtz second
      harmonic generation (SHG) test and the output power generated by the nanoparticle
      was compared with that of potassium di hydrogen phosphate (KDP). 

PMID- 24096061
TI  - Structure, photoluminescent properties and photocatalytic activities of a new
      Cd(II) metal-organic framework.
AB  - A new metal-organic framework, [Cd(TDC)(bix)(H2O)]n (H2TDC = thiophene-2,5
      dicarboxylic acid; bix = 1,4-bis(imidazol-1-ylmethyl)benzene), has been
      synthesized under hydrothermal conditions and structurally characterized by
      elemental analysis, infrared spectroscopy, thermogravimetric analysis, UV-vis and
      single X-ray diffraction. Cd-MOF is a 2D infinite layer framework, which is
      further interconnected by hydrogen-bond interactions leading to a 3D
      supramolecular architecture. The photoluminescent properties of the Cd-MOF were
      investigated and this compound shows intense fluorescent emissions in the solid
      state. In addition, it exhibits good photocatalytic activities for the
      degradation of methyl organic under UV light irradiation.

PMID- 24096062
TI  - Vibrational assignment of the spectral data, molecular dipole moment,
      polarizability, first hyperpolarizability, HOMO-LUMO and thermodynamic properties
      of 5-nitoindan using DFT quantum chemical calculations.
AB  - The vibrational spectra of 5-nitroindan (NI) was computed using B3LYP methodology
      with 6-31G(*) and 6-31G(**) basis sets. The FTIR and FT-Raman spectra were
      recorded in the region 4000-400 cm(-1) and 4000-50 cm(-1) respectively. A
      similarity was achieved between the observed and calculated frequencies by
      refinement of the scale factors. The (1)H and (13)CNMR chemical shifts results
      were also compared with the experimental values. The Mulliken charges, the values
      of electric dipole moment (MU) of the molecule were computed using DFT
      calculations. The first order hyperpolarizability (beta0) and related properties
      (beta, alpha0, and Deltaalpha) of both are calculated using B3LYP method on the
      finite-field approach. The electronic properties HOMO and LUMO energies are
      calculated. Thermodynamic properties (heat capacity, entropy and enthalpy) of the
      title compound were calculated.

PMID- 24096063
TI  - Experimental (XRD, FT-IR and UV-Vis) and theoretical modeling studies of Schiff
      base (E)-N'-((5-nitrothiophen-2-yl)methylene)-2-phenoxyaniline.
AB  - The Schiff base compound (E)-N'-((5-nitrothiophen-2-yl)methylene)-2
      phenoxyaniline has been synthesized and characterized by IR, UV-Vis, and X-ray
      diffraction (XRD) methods. The molecular geometry from X-ray experiment in the
      ground state has been compared using the density functional theory (DFT) with the
      6-311++G(d,p) basis set. The calculated results show that the optimized geometry
      can well reproduce the crystal structure, and the theoretical vibrational
      frequency values show good agreement with experimental values. By using TD-DFT
      method, electronic absorption spectra of the title compound have been predicted
      and a good agreement with the TD-DFT method and the experimental one is
      determined. The energetic behavior of the title compound in solvent media has
      been examined using B3LYP method with the 6-311++G(d,p) basis set by applying the
      Onsager and the integral equation formalism polarizable continuum model (IEF
      PCM). The predicted nonlinear optical properties of the title compound are
      greater than ones of urea. In addition, DFT calculations of the title compound,
      molecular electrostatic potential (MEP), natural bond orbital (NBO) and
      thermodynamic properties were performed at B3LYP/6-311++G(d,p) level of theory. 

PMID- 24096064
TI  - Molecular orbital studies (hardness, chemical potential, electronegativity and
      electrophilicity), vibrational spectroscopic investigation and normal coordinate
      analysis of 5-{1-hydroxy-2-[(propan-2-yl)amino]ethyl}benzene-1,3-diol.
AB  - FT-IR and FT-Raman spectra of 5-{1-hydroxy-2-[(propan-2-yl) amino] ethyl} benzene
      1,3-diol (abbrevi- 54 ated as HPAEBD) were recorded in the region 4000-450 cm(-1)
      and 4000-100 cm(-1) respectively. The structure of the molecule was optimized and
      the structural characteristics were determined by density functional theory
      (B3LYP) and HF method with 6-31 G(d,p) as basis set. The theoretical wave numbers
      were scaled and compared with experimental FT-IR and FT-Raman spectra. A detailed
      interpretation of the vibrational spectra of this compound has been made on the
      basis of the calculated Potential energy distribution (PED). Stability of the
      molecule arising from hyperconjugation and charge delocalization is confirmed by
      the natural bond orbital analysis (NBO). The results show that electron density
      (ED) in the sigma antibonding orbitals and E (2) energies confirm the occurrence
      of intra molecular charge transfer (ICT) within the molecule. The molecule
      orbital contributions were studied by using the total (TDOS), sum of alpha and
      beta electron (alphabetaDOS) density of States. Mulliken population analysis of
      atomic charges is also calculated. The calculated HOMO and LUMO energy gap shows
      that charge transfer occurs within the molecule. The electron density-based local
      reactivity descriptors such as Fukui functions were calculated to explain the
      chemical selectivity or reactivity site in this compound. On the basis of
      vibrational analyses, the thermodynamic properties of title compound at different
      temperatures have been calculated.

PMID- 24096065
TI  - Effect of beta-cyclodextrin on intra and intermolecular Michael addition of some
      catechol derivatives.
AB  - The oxidation reactions of catechol, dopamine and epinephrine have been studied
      in the absence and presence of N-methylaniline by UV-Vis. Spectrophotometry. A
      variety of reaction pathways (inter and intramolecular reactions) that followed
      by this oxidation have been observed depending on the nature of catechol
      derivatives. The observed homogeneous rate constants of the reactions were
      estimated by fitting the absorption time profiles for each reaction. The effect
      of beta-cyclodextrin and its inclusion complex has also been studied on the
      chosen reactions. The formation constants of the complexes of catechol, dopamine
      and epinephrine with beta-cyclodextrin as well as the rate constants of the
      reactions of free and complexed forms have been obtained by fitting the
      absorption-time spectra to a proposed kinetic-equilibrium model.

PMID- 24096066
TI  - Molecular structure, normal coordinate analysis, harmonic vibrational
      frequencies, NBO, HOMO-LUMO analysis and detonation properties of (S)-2-(2
      oxopyrrolidin-1-yl) butanamide by density functional methods.
AB  - Density functional theory (DFT) computations have become an efficient tool in the
      prediction of molecular structure, harmonic force fields, vibrational wave
      numbers as well as the IR and Raman intensities of pharmaceutically important
      molecule. In this work, we report harmonic vibrational frequencies, molecular
      structure, NBO and HOMO, LUMO analysis and detonation properties of (S)-2-(2
      oxopyrrolidin-1-yl) butanamide. The solid phase FT-IR and FT-Raman spectra of (S)
      2-(2-oxopyrrolidin-1-yl) butanamide were recorded in the region 4000-450 cm(-1)
      and 4000-50 cm(-1) respectively. Harmonic frequencies of this compound were
      determined and analyzed by DFT utilizing 6-31G(d,p), 6-31+G(d,p) basis sets. The
      assignments of the vibrational spectra have been carried out with the help of
      Normal Coordinate Analysis (NCA) following the Scaled Quantum Mechanical Force
      Field Methodology (SQMFF). The calculated infrared and Raman spectra of the title
      compounds were also stimulated utilizing the scaled force fields and the computed
      dipole derivatives for IR intensities and polarizability derivatives for Raman
      intensities. The change in electron density (ED) in the sigma(*) and pi(*)
      antibonding orbital's and stabilization energies E(2) have been calculated by
      Natural Bond Orbital (NBO) analysis to give clear evidence of stabilization
      originating in the hyperconjugation of hydrogen-bonded interaction. Heat of
      formation (HOF) and calculated density were estimated to evaluate detonation
      properties using Kamlet-Jacobs equations. The linear polarizability (alpha) and
      the first order hyperpolarizability (beta) values of the investigated molecule
      have been computed using DFT calculations. The calculated HOMO and LUMO energies
      show that charge transfer occurs within the molecule. The observed and calculated
      wave numbers are found to be in good agreement. On the basis of vibrational
      analyses, the thermodynamic properties of title compound at different
      temperatures have been calculated.

PMID- 24096067
TI  - Antioxidant activity and spectroscopic data of isoxanthohomol oxime and related
      compounds.
AB  - Oximes of isoxanthohumol (IXN), naringenin (N) and flavanone (FL) were
      synthesized with yields of 88-95% and their antioxidant activity was evaluated
      using the 1,1-diphenyl-2-picrylhydrazyl radical (DPPH) method. Although
      naringenin oxime (NOX) and flavanone oxime (FLOX) did not have any significant
      antioxidant effect (EC50=2.21 mM and 78.7 mM, respectively), isoxanthohumol oxime
      (IXNOX) showed a strong antioxidant activity (EC50=0.0411 mM), comparable to the
      activity of ascorbic acid (EC50=0.0181 mM). The structure of new compound IXNOX
      was established using (1)H NMR, (13)C NMR, IR and UV-VIS spectroscopy, by
      comparison to IXN, NOX and FLOX.

PMID- 24096068
TI  - Acute right ventricular myocarditis presenting with chest pain and syncope.
AB  - Myocarditis is assumed to involve both ventricles equally. Right ventricular
      predominant involvement is rarely described. A case of acute viral right
      ventricular myocarditis presenting with chest pain and syncope, grade 3
      atrioventricular block, right ventricular dilatation and free wall hypokinesia is
      reported. Cardiac MRI showed late enhancement of the right ventricular free wall
      without involvement of the left ventricle. Anti-Coxsackie A9 virus neutralising
      IgM-type antibodies titre was elevated. This case emphasises that manifestations
      of myocarditis can be limited to the right ventricle and should be considered in
      the differential diagnosis of right ventricular enlargement. 

PMID- 24096069
TI  - Overactive bladder after female genital mutilation/cutting (FGM/C) type III.
AB  - A 27-year-old Somali woman with type III a-b female genital mutilation/cutting,
      consulted because of slow micturition, voiding efforts, urgency and urge
      incontinence (overactive bladder). She also referred primary dysmenorrhoea and
      superficial dyspareunia making complete sexual intercourses impossible. We
      treated her by defibulation and biofeedback re-educative therapy. We also offered
      a multidisciplinary counselling. At 5 months follow-up, urgency and urge
      incontinence had resolved and she became pregnant. 

PMID- 24096071
TI  - Acalculous Phrygian cap cholecystitis.
AB  - We report a case of a 53-year-old Caucasian woman who presented with symptoms of
      cholecystitis; an ultrasound and CT scans showed a mass lesion associated with
      the gallbladder and no gallstones. Laparoscopic cholecystectomy and further
      histological analysis confirmed acalculous cholecystitis in a Phrygian cap
      gallbladder. 

PMID- 24096070
TI  - Adolescent idiopathic scoliosis in Down's syndrome.
AB  - Adolescent idiopathic scoliosis in Down's syndrome individuals has previously
      been reported in the context of institutionalised individuals and is of an
      iatrogenic nature, resulting from previous thoracotomy for congenital heart
      defects. We report the case of a male, non-institutionalised Down's syndrome
      individual, with no history of previous thoracic surgery and we follow the
      natural history of the condition, with particular reference to height velocity
      and curve progression velocity throughout puberty and successful treatment with a
      Boston thoracolumbosacral orthosis. 

PMID- 24096072
TI  - A not so simplex case of genital herpes.
AB  - We report the case of a 28-year-old, HIV-positive woman presenting with painful
      vesicular and ulcerating lesions in the ano-genital region caused by varicella
      zoster virus that appeared similar to herpes simplex infection. The case
      highlights that herpes zoster needs to be considered in the differential
      diagnosis of genital lesions, particularly in HIV-positive individuals, and the
      importance of virological diagnosis by PCR to direct appropriate management. 

PMID- 24096073
TI  - ACE-inhibitor induced angio-oedema treated with complement C1-inhibitor
      concentrate.
AB  - ACE-inhibitor is an antihypertensive drug which is increasingly used to treat a
      wide range of medical conditions. A known adverse reaction is angio-oedema of the
      head and neck, which can become fatal when the upper airway is involved, causing
      asphyxia. We present a Caucasian man, who developed severe angio-oedema of the
      tongue and floor of the mouth. He was successfully treated with complement C1
      concentrate causing the swelling to regress within 20 min. This treatment option
      can be an effective alternative to bradykinin antagonists, which might not be
      available in the emergency room, or more invasive measures like intubation or
      emergency airway puncture. 

PMID- 24096074
TI  - Cutaneous fistula due to remaining foreign bodies after penetrating neck injury.

PMID- 24096075
TI  - Acute post-traumatic endophthalmitis secondary to Propionibacterium acnes.
AB  - Propionibacterium acnes has rarely been reported as the causative organism in
      acute endophthalmitis following penetrating ocular trauma. We report a 53-year
      old man, who presented with best corrected vision of counting fingers at 2 m,
      <N36, in the right eye and clinical features suggestive of endophthalmitis
      following penetrating trauma with a tree branch 2 days earlier. Conjunctival
      swab, aqueous and vitreous tap were sent for aerobic, anaerobic and fungal
      culture. The patient was treated with intravitreal ceftazidime, vancomycin along
      with topical antibiotics and steroids. An aqueous anaerobic culture was positive
      for P acnes. At the fifth month follow-up, the best corrected vision had improved
      to 20/20, N6. Thus, a good visual outcome was achieved, following appropriate
      treatment of a rather unusual causative organism. 

PMID- 24096076
TI  - Effect of class IV laser therapy on chemotherapy-induced oral mucositis: a
      clinical and experimental study.
AB  - Oral mucositis (OM) is a serious and acute side effect in patients with cancer
      who receive chemotherapy or radiotherapy, often leading to the suspension of
      therapy and a need for opioid analgesic and enteral/parenteral nutrition, with an
      effect on patient survival. Among the various interventions proposed in OM
      management, laser therapy is becoming a recommended treatment option but has
      limitations due to its heterogeneous laser parameters. Here, we report on our
      successful clinical experience on the use of class IV laser therapy to treat OM
      induced by different chemotherapy regimens. To shed light on the mechanisms of
      action of laser therapy in improving OM resolution, we have developed an animal
      model of chemotherapy-induced OM, in which we compare the efficacy of the
      standard low-power laser therapy protocol with an innovative protocol, defined as
      high-power laser therapy. We show that high-power laser therapy is more effective
      than low-power laser therapy in improving OM lesion healing, reducing the
      inflammatory burden, and preserving tissue integrity. In addition, high-power
      laser therapy has been particularly effective in promoting the formation of new
      arterioles within the granulation tissue. Our results provide important insights
      into the mechanism of action of biostimulating laser therapy on OM in vivo and
      pave a way for clinical experimentation with the use of high-power laser therapy.

PMID- 24096077
TI  - Def-6, a novel regulator of small GTPases in podocytes, acts downstream of
      atypical protein kinase C (aPKC) lambda/iota.
AB  - The atypical protein kinase C (aPKC) isotypes PKClambda/iota and PKCzeta are both
      expressed in podocytes; however, little is known about differences in their
      function. Previous studies in mice have demonstrated that podocyte-specific loss
      of PKClambda/iota leads to a severe glomerular phenotype, whereas mice deficient
      in PKCzeta develop no renal phenotype. We analyzed various effects caused by
      PKClambda/iota and PKCzeta deficiency in cultured murine podocytes. In contrast
      to PKCzeta-deficient podocytes, PKClambda/iota-deficient podocytes exhibited a
      severe actin cytoskeletal phenotype, reduced cell size, decreased number of focal
      adhesions, and increased activation of small GTPases. Comparative microarray
      analysis revealed that the guanine nucleotide exchange factor Def-6 was
      specifically up-regulated in PKClambda/iota-deficient podocytes. In vivo Def-6
      expression is significantly increased in podocytes of PKClambda/iota-deficient
      mice. Cultured PKClambda/iota-deficient podocytes exhibited an enhanced membrane
      association of Def-6, indicating enhanced activation. Overexpression of
      aPKClambda/iota in PKClambda/iota-deficient podocytes could reduce the membrane
      associated expression of Def-6 and rescue the actin phenotype. In the present
      study, PKClambda/iota was identified as an important factor for actin
      cytoskeletal regulation in podocytes and Def-6 as a specific downstream target of
      PKClambda/iota that regulates the activity of small GTPases and subsequently the
      actin cytoskeleton of podocytes.

PMID- 24096078
TI  - Radiation induces diffusible feeder cell factor(s) that cooperate with ROCK
      inhibitor to conditionally reprogram and immortalize epithelial cells.
AB  - Both feeder cells and Rho kinase inhibition are required for the conditional
      reprogramming and immortalization of human epithelial cells. In the present
      study, we demonstrated that the Rho kinase inhibitor Y-27632, significantly
      suppresses keratinocyte differentiation and extends life span in serum-containing
      medium but does not lead to immortalization in the absence of feeder cells. Using
      Transwell culture plates, we further demonstrated that physical contact between
      the feeder cells and keratinocytes is not required for inducing immortalization
      and, more importantly, that irradiation of the feeder cells is required for this
      induction. Consistent with these experiments, conditioned medium was shown to
      induce and maintain conditionally immortalized cells, which was accompanied by
      increased telomerase expression. The activity of conditioned medium directly
      correlated with radiation-induced apoptosis of the feeder cells. Thus, the
      induction of conditionally reprogrammed cells is mediated by a combination of Y
      27632 and a diffusible factor (or factors) released by apoptotic feeder cells.

PMID- 24096080
TI  - A wavelet-based method to exploit epigenomic language in the regulatory region.
AB  - MOTIVATION: Epigenetic landscapes in the regulatory regions reflect binding
      condition of transcription factors and their co-factors. Identifying epigenetic
      condition and its variation is important in understanding condition-specific gene
      regulation. Computational approaches to explore complex multi-dimensional
      landscapes are needed. RESULTS: To study epigenomic condition for gene
      regulation, we developed a method, AWNFR, to classify epigenomic landscapes based
      on the detected epigenomic landscapes. Assuming mixture of Gaussians for a
      nucleosome, the proposed method captures the shape of histone modification and
      identifies potential regulatory regions in the wavelet domain. For accuracy
      estimation as well as enhanced computational speed, we developed a novel
      algorithm based on down-sampling operation and footprint in wavelet. We showed
      the algorithmic advantages of AWNFR using the simulated data. AWNFR identified
      regulatory regions more effectively and accurately than the previous approaches
      with the epigenome data in mouse embryonic stem cells and human lung fibroblast
      cells (IMR90). Based on the detected epigenomic landscapes, AWNFR classified
      epigenomic status and studied epigenomic codes. We studied co-occurring histone
      marks and showed that AWNFR captures the epigenomic variation across time.
      AVAILABILITY AND IMPLEMENTATION: The source code and supplemental document of
      AWNFR are available at http://wonk.med.upenn.edu/AWNFR.

PMID- 24096079
TI  - Novel interaction of ornithine decarboxylase with sepiapterin reductase regulates
      neuroblastoma cell proliferation.
AB  - Ornithine decarboxylase (ODC) is the sentinel enzyme in polyamine biosynthesis.
      Both ODC and polyamines regulate cell division, proliferation, and apoptosis.
      Sepiapterin reductase (SPR) catalyzes the last step in the biosynthesis of
      tetrahydrobiopterin (BH4), an essential cofactor of nitric oxide synthase, and
      has been implicated in neurological diseases but not yet in cancer. In this
      study, we present compelling evidence that native ODC and SPR physically
      interact, and we defined the individual amino acid residues involved in both
      enzymes using in silico protein-protein docking simulations. The resulting
      heterocomplex is a surprisingly compact structure, featuring two energetically
      and structurally equivalent binding modes both in monomer and in dimer
      conformations. The novel interaction between ODC and SPR proteins was confirmed
      under physiological conditions by co-immunoprecipitation and co-localization in
      neuroblastoma (NB) cells. Importantly, we showed that siRNA (small interfering
      RNA)-mediated knockdown of SPR expression significantly reduced endogenous ODC
      enzyme activity in NB cells, thus demonstrating the biological relevance of the
      ODC-SPR interaction. Finally, in a cohort of 88 human NB tumors, we found that
      high SPR mRNA expression correlated significantly with poor survival prognosis
      using a Kaplan-Meier analysis (log-rank test, P=5 * 10(-4)), suggesting an
      oncogenic role for SPR in NB tumorigenesis. In conclusion, we showed that ODC
      binds SPR and thus propose a new concept in which two well-characterized
      biochemical pathways converge via the interaction of two enzymes. We identified
      SPR as a novel regulator of ODC enzyme activity and, based on clinical evidence,
      present a model in which SPR drives ODC-mediated malignant progression in NB.

PMID- 24096081
TI  - Non-additive interactions between mitochondrial complex IV blockers and hypoxia
      in rat carotid body responses.
AB  - The metabolic hypothesis of carotid body chemoreceptor hypoxia transduction
      proposes an impairment of ATP production as the signal for activation. We
      hypothesized that mitochondrial complex IV blockers and hypoxia would act
      synergistically in exciting afferent nerve activity. Following a pre-treatment
      with low dosage sodium cyanide (10-20MUM), the hypoxia-induced nerve response was
      significantly reduced along with hypoxia-induced catecholamine release. However,
      in isolated glomus cells, the intracellular calcium response was enhanced as
      initially predicted. This suggests a cyanide-mediated impairment in the step
      between the glomus cell intracellular calcium rise and neurotransmitter release
      from secretory vesicles. Administration of a PKC blocker largely reversed the
      inhibitory actions of cyanide on the neural response. We conclude that the
      expected synergism between cyanide and hypoxia occurs at the level of glomus cell
      intracellular calcium but not at downstream steps due to a PKC-dependent
      inhibition of secretion. This suggests that at least one regulatory step beyond
      the glomus cell calcium response may modulate the magnitude of chemoreceptor
      responsiveness. 

PMID- 24096083
TI  - Weight stigma and narrative resistance evident in online discussions of obesity.
AB  - This study sampled 2872 obesity-relevant comments from three years of interest
      from a multi-topic online message board. An inductive thematic analysis was
      conducted and three themes were evident: reactions and responses to obesity and
      obese bodies, diminished status of overweight/obese persons, and narrative
      resistance to an overweight/obese identity. Obesity stigma was pervasive and the
      discussion of the issue revealed it to be highly acceptable. Consistent with
      previous research, dominant representations of obese persons as lazy and
      unintelligent with poor self-control were evident. The analysis provided valuable
      insight into experiences of explicit stigma, the social and psychological
      repercussions of overt stigma and norms regarding the perception of obese bodies.
      There was a prevailing notion that the opinions and insights of overweight and
      obese persons on the issue of weight were not credible and were perceived as
      biased. Furthermore, individuals sought to distance themselves from the
      undesirable labels of 'overweight' and 'obese' by enacting narrative resistance
      to negotiate the social meaning of excess weight and endeavouring to place
      themselves on the 'safe' side of this boundary. These results highlight the
      pervasive nature of weight stigma and the social acceptability of such attitudes
      and beliefs. Furthermore, it highlights the richness of data that may be obtained
      by examining social media interactions as a window into the naturally-occurring
      discourse on obesity and stigma. 

PMID- 24096082
TI  - Questionnaire and laboratory measures of eating behavior. Associations with
      energy intake and BMI in a community sample of working adults.
AB  - PURPOSE: The present research compared a self-report measure of usual eating
      behaviors with two laboratory-based behavioral measures of food reward and food
      preference. METHODS: Eating behaviors were measured among 233 working adults. A
      self-report measure was the Three Factor Eating Questionnaire (TFEQ) Restraint,
      Disinhibition and Hunger subscales. Laboratory measures were the (RVF) and
      Explicit Liking (EL) and Implicit Wanting (IW) for high fat food. Outcome
      measures were body mass index (BMI), and energy intake measured using three 24-h
      dietary recalls. RESULTS: Significant bivariate associations were observed
      between each of the eating behavior measures and energy intake, but only
      Disinhibition and Hunger were associated with BMI. Multiple regression results
      showed RVF and EL and IW predicted energy intake independent of the TFEQ scales
      but did not predict BMI. CONCLUSION: Laboratory and self-report measures capture
      unique aspects of individual differences in eating behaviors that are associated
      with energy intake.

PMID- 24096084
TI  - Taking weight-loss supplements may elicit liberation from dietary control. A
      laboratory experiment.
AB  - Given that changes in diet and exercise habits are difficult to initiate and
      maintain, the use of weight-loss supplements has become an appealing alternative
      approach to weight management for many individuals. The current research examined
      whether the use of weight-loss supplements induced overly optimistic assessments
      of progress toward weight reduction, leading to psychological abdication of
      dietary regulation. Participants were randomly assigned to take either an
      identified placebo or a purported weight-loss supplement (actually the same
      placebo). Each participant reported perceived progress toward weight reduction
      following the manipulation. Consumption of snacks in a taste test and choice of
      sugary drinks were recorded. The results showed that participants receiving a
      purported supplement ate more in a taste task and preferred larger quantities of
      sugar in their reward drinks than did controls. Mediation analysis supported that
      the perception of progress toward weight reduction contributed to the liberating
      effect. Using weight-loss supplements may increase perceived progress toward
      weight reduction but decrease dietary self-regulation. These thought-provoking
      findings can serve as a basis for educating the public about the myth that they
      are free to feel liberated from the need to regulate their eating when using
      weight-loss supplements. 

PMID- 24096085
TI  - MAVS-dependent IRF3/7 bypass of interferon beta-induction restricts the response
      to measles infection in CD150Tg mouse bone marrow-derived dendritic cells.
AB  - Measles virus (MV) infects CD150Tg/Ifnar (IFN alpha receptor)(-/-) mice but not
      CD150 (a human MV receptor)-transgenic (Tg) mice. We have shown that bone marrow
      derived dendritic cells (BMDCs) from CD150Tg/Ifnar(-/-) mice are permissive to MV
      in contrast to those from simple CD150Tg mice, which reveals a crucial role of
      type I interferon (IFN) in natural tropism against MV. Yet, the mechanism whereby
      BMDCs produce initial type I IFN has not been elucidated in MV infection. RNA
      virus infection usually allows cells to generate double-stranded RNA and induce
      activation of IFN regulatory factor (IRF) 3/7 transcription factors, leading to
      the production of type I IFN through the retinoic acid-inducible gene I (RIG
      I)/melanoma differentiation-associated gene 5 (MDA5)-mitochondrial antiviral
      signaling protein (MAVS) pathway. In mouse experimental BMDCs models, we found
      CD150Tg/Mavs(-/-)BMDCs, but not CD150Tg/Irf3(-/-)/Irf7(-/-)BMDCs, permissive to
      MV. IFN-alpha/beta were not induced in MV-infected CD150Tg/Mavs(-/-)BMDCs, while
      IFN-beta was subtly induced in CD150Tg/Irf3(-/-)/Irf7(-/-)BMDCs. In vivo systemic
      infection was therefore established by transfer of MV-infected CD150Tg/Mavs(-/-)
      BMDCs to CD150Tg/Ifnar(-/-) mice. These data indicate that MAVS-dependent, IRF3/7
      independent IFN-beta induction triggers the activation of the IFNAR pathway so as
      to restrict the spread of MV by infected BMDCs. Hence, MAVS participates in the
      initial induction of type I IFN in BMDCs and IFNAR protects against MV spreading.
      We also showed the importance of IL-10-producing CD4(+) T cells induced by MV
      infected BMDCs in vitro, which may account for immune modulation due to the
      functional aberration of DCs.

PMID- 24096086
TI  - Efficiency of RNA extraction from selected bacteria in the context of biogas
      production and metatranscriptomics.
AB  - Understanding the microbial population in anaerobic digestion is an essential
      task to increase efficient substrate use and process stability. The metabolic
      state, represented e.g. by the transcriptome, of a fermenting system can help to
      find markers for monitoring industrial biogas production to prevent failures or
      to model the whole process. Advances in next-generation sequencing make
      transcriptomes accessible for large-scale analyses. In order to analyze the
      metatranscriptome of a mixed-species sample, isolation of high-quality RNA is the
      first step. However, different extraction methods may yield different
      efficiencies in different species. Especially in mixed-species environmental
      samples, unbiased isolation of transcripts is important for meaningful
      conclusions. We applied five different RNA-extraction protocols to nine taxonomic
      diverse bacterial species. Chosen methods are based on various lysis and
      extraction principles. We found that the extraction efficiency of different
      methods depends strongly on the target organism. RNA isolation of gram-positive
      bacteria was characterized by low yield whilst from gram-negative species higher
      concentrations can be obtained. Transferring our results to mixed-species
      investigations, such as metatranscriptomics with biofilms or biogas plants, leads
      to the conclusion that particular microorganisms might be over- or
      underrepresented depending on the method applied. Special care must be taken when
      using such metatranscriptomics data for, e.g. process modeling. 

PMID- 24096087
TI  - Temperature dependence of binding and catalysis for human serum
      arylesterase/paraoxonase.
AB  - The influence of temperature upon the hydrolysis of phenyl acetate, catalysed by
      purified human serum arylesterase/paraoxonase (E. C. 3.1.8.1), was studied in the
      temperature range 10  degrees C-40  degrees C by spectrophotometry in TRIS
      buffer, pH 8.0, using both initial rate analysis and progress curve analysis. The
      kinetic parameters (catalytic constant k(cat); Michaelis constant K(m); product
      inhibition constant K(p)) were determined by nonlinear regression. All parameters
      increased with temperature, but the ratios k(cat)/K(m) and K(p)/K(m) remained
      practically constant. Binding of both substrate and reaction product (phenol) was
      exothermic. A negative entropic term accounted for about 50% of the enthalpy
      change for both the binding and catalytic steps. Thermodynamic analysis suggested
      that: (1) the rate-limiting step is the nucleophilic attack of the carbonyl group
      of the substrate by a water molecule, (2) the active site is preorganized with no
      induced fit, (3) the enzyme-bound calcium plays an important role in stabilizing
      both the substrate and the transition state. The practical implications of these
      results are discussed.

PMID- 24096088
TI  - Differences in the acuity of the Approximate Number System in adults: the effect
      of mathematical ability.
AB  - It is largely admitted that processing numerosity relies on an innate Approximate
      Number System (ANS), and recent research consistently observed a relationship
      between ANS acuity and mathematical ability in childhood. However, studies
      assessing this relationship in adults led to contradictory results. In this
      study, adults with different levels of mathematical expertise performed two tasks
      on the same pairs of dot collections, based either on numerosity comparison or on
      cumulative area comparison. Number of dots and cumulative area were congruent in
      half of the stimuli, and incongruent in the other half. The results showed that
      adults with higher mathematical ability obtained lower Weber fractions in the
      numerical condition than participants with lower mathematical ability. Further,
      adults with lower mathematical ability were more affected by the interference of
      the continuous dimension in the numerical comparison task, whereas conversely
      higher-expertise adults showed stronger interference of the numerical dimension
      in the continuous comparison task. Finally, ANS acuity correlated with arithmetic
      performance. Taken together, the data suggest that individual differences in ANS
      acuity subsist in adulthood, and that they are related to mathematical ability. 

PMID- 24096089
TI  - The PARK2 gene is involved in the maintenance of pancreatic beta-cell functions
      related to insulin production and secretion.
AB  - Several association studies have implicated the PARK2 gene that encodes parkin-
      the key molecule orchestrating the mitochondrial quality control system--as a
      candidate susceptibility gene for diabetes. A total of 7551 unrelated Korean KARE
      cohort subjects were analyzed to investigate the association between the PARK2
      single nucleotide polymorphism (SNP) and quantitative glycemic traits. Two SNPs,
      rs10455889 and rs9365294, were significantly associated with fasting plasma
      glucose level (p=~1.2*10(-4)) and insulin secretion indices (p=~7.4*10(-5)) in
      male KARE subjects. Parkin was expressed predominantly in the rat pancreatic
      islets. Downregulation of the Park2 gene in rat INS-1 beta-cells resulted in a
      significant decrease in the glucose-stimulated insulin secretion, intracellular
      insulin gene expression, and intracellular ATP level. The Park2-depleted beta
      cells also exhibited increased mitochondrial fragmentation and ROS production and
      decreased mitochondrial membrane potential. Both population-based statistical
      evaluation and experimental evidence demonstrated a fundamental role of the PARK2
      gene in the maintenance of beta-cell function.

PMID- 24096090
TI  - The identification and expression of the full-length HtrA2 gene from Penaeus
      monodon (black tiger shrimp).
AB  - HtrA2 is an apoptosis-activating protein to enhance the apoptotic process by
      preventing the formation of the IAP-caspase complex, thus freeing caspase to
      trigger the apoptosis pathway. Here, we presented the full-length sequence of
      HtrA2 from the black tiger shrimp (PmHtrA2). The full-length PmHtrA2 transcript
      was 1403 bp with a 1338 bp open reading frame encoding 445 amino acids and
      contains 5 conserved domains, namely, a mitochondrial targeting signal (MTS), a
      transmembrane (TM) domain, an IAP-binding motif (IBM), a serine protease domain,
      and a PDZ domain normally found in HtrA2 proteins of other organisms. The mature
      form of PmHtrA2 was cloned into the pET28b(+) and pET15bThio vectors, and the
      expression of the protein was compared in Escherichia coli BL21 DE3 and BL21 RIL
      (CodonPlus) strains. Greater quantities of stable and soluble PmHtrA2 were
      expressed as a thioredoxin fusion protein in E. coli BL21 RIL (CodonPlus) cells
      with the recombinant pET15bThio-PmHtrA2 vector. To investigate the expression of
      PmHtrA2 in shrimp, the crude proteins from several shrimp tissues were imaged by
      Western blot using the polyclonal antibody specific to the recombinant PmHtrA2.
      The expression of the 47-kDa immature PmHtrA2 protein could be detected in shrimp
      lysates from the gills and the muscles. This study is the first to report the
      full-length PmHtrA2 gene, which is functional in black tiger shrimp and will lead
      to more focused studies on the function of PmHtrA2 in apoptosis regulation during
      immune responses to viral infection in shrimp.

PMID- 24096091
TI  - Expression, purification and biological characterization of human vasostatin120
      180 in Pichia pastoris.
AB  - Angiogenesis is a major feature of tumor growth and metastasis. As such,
      targeting the tumor neovasculature is an attractive strategy for effective cancer
      therapy. Angiogenesis inhibitors have strong therapeutic potential as antitumor
      agents in suppressing tumor growth and metastatic progression. Vasostatin, the N
      terminal domain of calreticulin, is a potent angiogenesis inhibitor. Our
      laboratory previously reported a strategy for expression and purification of
      human vasostatin120-180 (VAS) in a GST-tagged fusion form using Escherichia coli
      expression system. However, the yield of 7.2 mg per liter of culture was
      relatively low and the protein activity was also limited. In this study, the
      biologically active and soluble VAS was cloned and expressed in Pichia pastoris.
      The yield of the active VAS was about 20 mg/L of the P. pastoris culture medium.
      The recombinant protein was purified to homogeneity, and confirmed to be
      biologically active. The recombinant VAS could efficiently inhibit angiogenesis
      and endothelial cell proliferation in vitro. Moreover, the P. pastoris-derived
      VAS showed relatively higher protein activity than E. coli-derived VAS.
      Furthermore, it can inhibit in vivo xenograft tumor growth and prolong the tumor
      doubling time significantly by inhibiting angiogenesis. Taken together, this is
      the first report on the heterologous expression of VAS in P. pastoris, and P.
      pastoris is a highly efficient and cost-effective expression system for large
      amount production of biologically active recombinant VAS for potential
      therapeutic application.

PMID- 24096092
TI  - Docetaxel-induced hypersensitivity pneumonitis mimicking lymphangitic
      carcinomatosis in a patient with metastatic adenocarcinoma of the lung.
AB  - Docetaxel belongs to the taxane family of anti-cancer drugs, which are commonly
      used in non-small cell lung cancers. They stabilize microtubules by preventing
      depolymerization, resulting in cell death. Pneumonitis is an uncommon side effect
      of docetaxel. We report a case of docetaxel induced hypersensitivity pneumonitis
      mimicking lymphangitic carcinomatosis in a patient with metastatic adenocarcinoma
      of the lung. 

PMID- 24096093
TI  - Post-saccadic oscillations in eye movement data recorded with pupil-based eye
      trackers reflect motion of the pupil inside the iris.
AB  - Current video eye trackers use information about the pupil center to estimate
      orientation and movement of the eye. While dual Purkinje eye trackers suffer from
      lens wobble and scleral search coils may be influenced by contact lens slippage
      directly after saccades, it is not known whether pupil-based eye trackers
      produces similar artifacts in the data. We recorded eye movements from
      participants making repetitive, horizontal saccades and compared the movement in
      the data with pupil- and iris movements extracted from the eye images. Results
      showed that post-saccadic instabilities clearly exist in data recorded with a
      pupil-based eye tracker. They also exhibit a high degree of reproducibility
      across saccades and within participants. While the recorded eye movement data
      correlated well with the movement of the pupil center, the iris center showed
      only little post-saccadic movement. This means that the pupil moves relative to
      the iris during post-saccadic eye movements, and that the eye movement data
      reflect pupil movement rather than eyeball rotation. Besides introducing
      inaccuracies and additional variability in the data, the pupil movement inside
      the eyeball influences the decision of when a saccade should end and the
      subsequent fixation should begin, and consequently higher order analyses based on
      fixations and saccades.

PMID- 24096094
TI  - Anti-apoptotic Bcl-2 family member Mcl-1 regulates cell viability and bone
      resorbing activity of osteoclasts.
AB  - Myeloid cell leukemia sequence 1 (Mcl-1) is an anti-apoptotic Bcl-2 family
      protein and an immediate early gene expressed during myeloid leukemia cell line
      differentiation. We analyzed the expression and function of Mcl-1 in osteoclasts.
      Mcl-1 protein exhibited a short half-life in osteoclasts caused by its
      degradation in the ubiquitin-proteasome system. Mcl-1 had no effect on osteoclast
      differentiation, but its overexpression prolonged osteoclast survival and
      suppressed the bone-resorbing activity of these cells, as determined by pit
      formation assay. Conversely, Mcl-1 depletion suppressed osteoclast survival and
      increased bone resorption. This negative role for Mcl-1 on the bone-resorptive
      activities of osteoclasts may be caused by the increase in adenosine
      triphosphate/adenosine diphosphate ratio. Finally, we showed that the local
      deletion of Mcl-1 by the injection of the Cre adenovirus into the calvaria of
      Mcl1(fl/fl) mice significantly affected GST-RANKL-induced bone resorption in
      vivo. These results demonstrated that Mcl-1 positively regulates cell viability
      and negatively regulates the bone-resorbing activity of osteoclasts both in vitro
      and in vivo. 

PMID- 24096095
TI  - 'Pucker sign' an indicator of irreducible knee dislocation.

PMID- 24096097
TI  - Reproductive value in graph-structured populations.
AB  - Evolutionary graph theory has grown to be an area of intense study. Despite the
      amount of interest in the field, it seems to have grown separate from other
      subfields of population genetics and evolution. In the current work I introduce
      the concept of Fisher's (1930) reproductive value into the study of evolution on
      graphs. Reproductive value is a measure of the expected genetic contribution of
      an individual to a distant future generation. In a heterogeneous graph-structured
      population, differences in the number of connections among individuals translate
      into differences in the expected number of offspring, even if all individuals
      have the same fecundity. These differences are accounted for by reproductive
      value. The introduction of reproductive value permits the calculation of the
      fixation probability of a mutant in a neutral evolutionary process in any graph
      structured population for either the moran birth-death or death-birth process. 

PMID- 24096096
TI  - Simplified validated prognostic model for progression-free survival after
      autologous transplantation for hodgkin lymphoma.
AB  - Hodgkin lymphoma (HL) prognostic models based on factors measured at time of
      autologous hematopoietic cell transplantation (AHCT) are limited by small sample
      sizes. Models based on information at diagnosis are often not uniformly collected
      or available at transplantation. We propose an easily implementable prognostic
      model for progression-free survival (PFS) post-AHCT based on factors available at
      transplantation in a large international cohort of HL patients. The outcomes of
      728 AHCT recipients for relapsed/refractory HL were studied. Patients were
      randomly selected for model development (n = 337) and validation (n = 391). The
      multivariate model identified 4 major adverse risk factors at the time of AHCT
      with the following relative weights: Karnofsky performance score <90 and
      chemotherapy resistance at AHCT were each assigned 1 point, whereas at least 3
      chemotherapy regimens pre-AHCT and extranodal disease at AHCT were each assigned
      2 points. Based on the total score summed for the 4 adverse risk factors, 3 risk
      groups were identified: low (score = 0), intermediate (score = 1 to 3), or high
      (score = 4 to 6). The 4-year PFS for the low- (n = 176), intermediate- (n = 261),
      and high- (n = 283) risk groups were 71% (95% confidence interval [CI], 63% to
      78%), 60% (95% CI, 53% to 66%), and 42% (95% CI, 36% to 49%), respectively. The
      prognostic model was validated in an independent cohort. The Center for
      International Blood and Marrow Transplant Research model is based on factors
      easily available at the time of AHCT and discriminates patients with favorable
      post-AHCT outcomes as well as an intermediate-risk group. This model should
      assist in the prospective evaluation of alternative treatment strategies.

PMID- 24096098
TI  - A unifying framework reveals key properties of multilevel selection.
AB  - Natural selection can act at multiple biological levels, often in opposing
      directions. Viral evolution is an important example, with selection occurring
      both within infected hosts and between hosts via transmission. A fast-replicating
      virus may outcompete a slower strain within the same host, however, if rapid
      viral replication incapacitates the host, this fast-replicating virus may not be
      transmitted as frequently as its slower counterpart. Such examples of
      antagonistic multilevel selection arise across biological taxa and scales, from
      microbial public goods production to male mating strategies. A general formalism
      for describing and analyzing these diverse systems can identify their common
      underlying properties. Here I introduce such a unifying framework, which can be
      intuitively visualized as a stochastic ball-and-urn process. This ball-and-urn
      process illustrates the dynamics of antagonistic selective forces and allows the
      systematic derivation of properties with little or no dependence on model
      parameterization. These properties are consistent with previous studies, both
      theoretical and empirical, of multilevel selection. In particular I show that
      selection at the group level is favored when group-level events occur frequently
      relative to individual-level events, when there is little or no mutation, and
      when there are many groups relative to the number of individuals in each group.
      This approach demonstrates how multilevel selection can be understood as a
      general biological phenomenon, and identifies recurring characteristics that may
      be independent of specific biological contexts. 

PMID- 24096099
TI  - Animal path integration: a model of positional uncertainty along tortuous paths.
AB  - Exact closed form mathematical solutions are reported which quantify the dynamic
      uncertainty resulting from path integration (PI) along tortuous paths. Based on a
      correlated random walk model, the derived results quantify positional estimation
      error moments with and without a compass, in discrete and continuous time.
      Consistent with earlier studies on attempted straight-line navigation, using a
      compass significantly reduces the uncertainty during PI, making purely idiothetic
      PI biologically implausible except over short distances. Examples are used to
      illustrate the contributions of angular noise, linear noise and path tortuosity,
      under different conditions. Linear noise is shown to be relatively more important
      with a compass while angular noise is more important without. It is shown that
      increasing path tortuosity decreases positional uncertainty, true for long and
      short journeys, irrespective of whether a compass is used, or the level of noise.
      In contrast, reducing angular noise also reduces uncertainty, but only below some
      critical level of noise. Using canonical equations of PI, it is shown that polar
      PI using a compass accumulates uncertainty in a manner similar to Cartesian PI
      without a compass. Issues of data sampling bias and intermittent use of a compass
      are also considered for PI along tortuous paths. 

PMID- 24096100
TI  - Evidence for dimer/tetramer equilibrium in Trypanosoma brucei 6-phosphogluconate
      dehydrogenase.
AB  - 6-Phosphogluconate dehydrogenase (6PGDH), the third enzyme of the pentose
      phosphate pathway (PPP), is essential for biosyntheses and oxidative stress
      defence. It also has the function of depleting 6PG, whose accumulation induces
      cell senescence. 6PGDH is a proposed drug target for African trypanosomiasis
      caused by Trypanosoma brucei and for other microbial infections and cancer. Gel
      filtration, density gradient sedimentation, cross-linking and dynamic light
      scattering were used to assay the oligomerization state of T. brucei 6PGDH in the
      absence and presence of several ligands. The enzyme displays a dimer-tetramer
      equilibrium and NADPH (but not NADP) reduces the rate of approach to equilibrium,
      while 6PG is able to antagonize the NADPH effect. The different behaviour of the
      two forms of coenzyme appears to be related to the differences in DeltaCp, with
      NADP binding DeltaCp closer to what is expected of crystallographic structures,
      while NADPH DeltaCp is three times larger. The estimated dimer-tetramer
      association constant is 1.5.10(6)M(-1), and the specific activity of the tetramer
      is about 3 fold higher than the specific activity of the dimer. Thus, cellular
      conditions promoting tetramer formation could allow an efficient clearing of 6PG.
      Experiments carried out on sheep liver 6PGDH indicate that tetramerization is a
      specificity of the parasite enzyme. 

PMID- 24096101
TI  - Comparative analysis of Leishmania exoproteomes: implication for host-pathogen
      interactions.
AB  - Leishmaniasis is a vector-borne disease caused by the protozoa Leishmania. We
      have analyzed and compared the sequences of three experimental exoproteomes of
      Leishmania promastigotes from different species to determine their specific
      features and to identify new candidate proteins involved in interactions of
      Leishmania with the host. The exoproteomes differ from the proteomes by a
      decrease in the average molecular weight per protein, in disordered amino acid
      residues and in basic proteins. The exoproteome of the visceral species is
      significantly enriched in sites predicted to be phosphorylated as well as in
      features frequently associated with molecular interactions (intrinsic disorder,
      number of disordered binding regions per protein, interaction and/or trafficking
      motifs) compared to the other species. The visceral species might thus have a
      larger interaction repertoire with the host than the other species. Less than 10%
      of the exoproteomes contain heparin-binding and RGD sequences, and ~30% the host
      targeting signal RXLXE/D/Q. These latter proteins might thus be exported inside
      the host cell during the intracellular stage of the infection. Furthermore we
      have identified nine protein families conserved in the three exoproteomes with
      specific combinations of Pfam domains and selected eleven proteins containing at
      least three interaction and/or trafficking motifs including two splicing factors,
      phosphomannomutase, 2,3-bisphosphoglycerate-independent phosphoglycerate mutase,
      the paraflagellar rod protein-1D and a putative helicase. Their role in host
      Leishmania interactions warrants further investigation but the putative ATP
      dependent DEAD/H RNA helicase, which contains numerous interaction motifs, a host
      targeting signal and two disordered regions, is a very promising candidate. 

PMID- 24096102
TI  - A common mechanism underlying amyloid fibrillation and protein crystallization
      revealed by the effects of ultrasonication.
AB  - Protein crystals form in supersaturated solutions via a nucleation and growth
      mechanism. The amyloid fibrils of denatured proteins also form via a nucleation
      and growth mechanism. This similarity suggests that, although protein crystals
      and amyloid fibrils are distinct in their morphologies, both processes can be
      controlled in a similar manner. It has been established that ultrasonication
      markedly accelerates the formation of amyloid fibrils and simultaneously breaks
      them down into fragmented fibrils. In this study, we investigated the effects of
      ultrasonication on the crystallization of hen egg white lysozyme and glucose
      isomerase from Streptomyces rubiginosus. Protein crystallization was monitored by
      light scattering, tryptophan fluorescence, and light transmittance. Repeated
      ultrasonic irradiations caused the crystallization of lysozyme and glucose
      isomerase after cycles of irradiations. The size of the ultrasonication-induced
      crystals was small and homogeneous, and their numbers were larger than those
      obtained under quiescent conditions. Switching off ultrasonic irradiation when
      light scattering or tryptophan fluorescence began to change resulted in the
      formation of larger crystals due to the suppression of the further nucleation and
      fractures in preformed crystals. The results indicate that protein
      crystallization and amyloid fibrillation are explained on the basis of a common
      phase diagram in which ultrasonication accelerates the formation of crystals or
      crystal-like amyloid fibrils as well as fragmentation of preformed crystals or
      fibrils. 

PMID- 24096103
TI  - Pharmacogenetic workup of perioperative serotonin syndrome.
AB  - Serotonin syndrome is gaining attention in perioperative and chronic pain
      settings due to the growing prevalence of multimodal therapies that increase
      serotonin levels and thereby heighten patient risk. A patient's genetic make-up
      may further increase the risk of serotonin syndrome. A case of serotonin syndrome
      on emergence after general anesthesia is presented. A subsequent cytochrome
      P4502D6 genetic test result suggested a potential alteration in metabolism. For
      this patient, who was taking combination antidepressant medications and receiving
      common perioperative medicines, additive pharmacodynamic effects converged with a
      pharmacogenetic predisposition, resulting in serotonin syndrome. 

PMID- 24096104
TI  - Green tea (Camellia sinensis) administration induces expression of immune
      relevant genes and biochemical parameters in rainbow trout (Oncorhynchus mykiss).
AB  - Present study elucidates the efficacy of green tea (Camellia sinensis) on growth
      performance, immune and antioxidant systems and cytokine gene expression in
      rainbow trout tissues. Green tea was supplemented at 20, 100, and 500 mg kg(-1)
      diet and fed to fish (average weight: 23.5 g) for 35 days. No remarkable changes
      in growth performance were observed among all test groups. Lower lipid
      peroxidation product and higher superoxide dismutase activity were noted in fish
      received the medium dose of green tea. Significant increase in serum bactericidal
      activity and total protein were recorded in all treatment groups. All doses of
      green tea up-regulated Interleukin-1beta transcription in the spleen, while
      Interleukin-1beta mRNA level decreased significantly in the kidney of low dose of
      green tea. Interleukin-6 mRNA level was up-regulated in the spleen of high dose
      of green tea and liver of middle and high doses of green tea. High dose and
      medium dose of green tea up-regulated the interleukin-8 transcription in the
      kidney and liver, respectively. Meanwhile, green tea inhibited the production of
      interleukin-10 in all treatment groups compared with control group. Medium dose
      of green tea up-regulated tumor necrosis factor-alpha transcription in all fish
      tissues, while high dose and low dose of green tea enhanced tumor necrosis factor
      alpha mRNA levels in the kidney and spleen, respectively. Present study suggests
      that green tea especially at 100 mg kg(-1) feed may effectively enhance the
      antioxidant system and immune system in rainbow trout.

PMID- 24096105
TI  - Quality of CPR performed by trained bystanders with optimized pre-arrival
      instructions.
AB  - OBJECTIVE: Telephone-CPR (T-CPR) can increase initiation of bystander CPR. We
      wanted to study if quality oriented continuous T-CPR would improve CPR
      performance vs. standard T-CPR. METHOD: Ninety-five trained rescuers aged 22-69
      were randomized to standard T-CPR or experimental continuous T-CPR (comprises
      continuous instructions, questions and encouragement). They were instructed to
      perform 10 min of chest compressions-only on a manikin, which recorded CPR
      performance in a small, confined kitchen. Three video-cameras captured algorithm
      time data, CPR technique and communication. Demography and training experience
      were captured during debriefing. RESULTS: Participants receiving continuous T-CPR
      delivered significantly more chest compressions (median 1000 vs. 870
      compressions, p=0.014) and compressed more frequently to a compression rate
      between 90 and 120 min(-1) (median 87% vs. 60% of compressions, p<0.001),
      compared to those receiving standard T-CPR. This also resulted in less time
      without compressions after CPR had started (median 12s vs. 64 s, p<0.001), but
      longer time interval from initiating contact with dispatcher to first chest
      compression (median 144 s vs. 84 s, p<0.001). There was no difference in chest
      compression depth (mean 47 mm vs. 48 mm, p = 0.90) or in demography, education
      and previous CPR training between the groups. CONCLUSION: In our simulated
      scenario with CPR trained lay rescuers, experimental continuous T-CPR gave better
      chest compression rate and less hands-off time during CPR, but resulted in
      delayed time to first chest compression compared to standard T-CPR instructions.

PMID- 24096106
TI  - Alterations of irisin concentrations in saliva and serum of obese and normal
      weight subjects, before and after 45 min of a Turkish bath or running.
AB  - The purpose of this study was to ascertain (1) whether human saliva contains
      irisin and whether its level correlates with serum irisin concentration, (2)
      whether salivary glands, eccrine glands and sebaceous glands in human skin
      produce irisin, (3) how the changes in saliva and serum irisin concentrations
      after the Turkish bath at 47 +/- 3 degrees C compare with the changes caused by
      moderate exercise in obese and normal weight subjects. Seven obese male subjects
      and seven normal weight subjects were enrolled for Turkish bath. Seven obese male
      subjects and seven normal weight subjects were also enrolled for moderate outdoor
      exercise, and thirteen male normal weight subjects neither exercised nor showered
      at the Turkish bath. From each participant, 1.5 ml of saliva and 5 ml blood were
      collected simultaneously before and after the moderate exercise and Turkish bath.
      Salivary glands and eccrine and sebaceous glands in the skin were screened
      immunohistochemically for irisin while serum and saliva irisin were measured with
      an ELISA. Submandibular glands, eccrine glands and sebaceous glands in the human
      skin showed strong irisin immunoreactivity. Human saliva contained irisin and its
      level was significantly higher than the serum levels in both obese and normal
      weight subjects. However, irisin concentrations were more markedly increased in
      both saliva and serum samples from subjects who had showered at a Turkish bath
      than in obese subjects who had exercised or in normal weight subjects. Human
      submandibular glands, eccrine sweat glands and sebaceous glands synthesize
      irisin.

PMID- 24096107
TI  - Antimicrobial activity of nisin against the swine pathogen Streptococcus suis and
      its synergistic interaction with antibiotics.
AB  - Streptococcus suis serotype 2 is known to cause severe infections in pigs,
      including meningitis, endocarditis and pneumonia. Furthermore, this bacterium is
      considered an emerging zoonotic agent. Recently, increased antibiotic resistance
      in S. suis has been reported worldwide. The objective of this study was to
      evaluate the potential of nisin, a bacteriocin of the lantibiotic class, as an
      antibacterial agent against the pathogen S. suis serotype 2. In addition, the
      synergistic activity of nisin in combination with conventional antibiotics was
      assessed. Using a plate assay, the nisin-producing strain Lactococcus lactis ATCC
      11454 proved to be capable of inhibiting the growth of S. suis (n=18) belonging
      to either sequence type (ST)1, ST25, or ST28. In a microdilution broth assay, the
      minimum inhibitory concentration (MIC) of purified nisin ranged between 1.25 and
      5 MUg/mL while the minimum bactericidal concentration (MBC) was between 5 and 10
      MUg/mL toward S. suis. The use of a capsule-deficient mutant of S. suis indicated
      that the presence of this polysaccharidic structure has no marked impact on
      susceptibility to nisin. Following treatment of S. suis with nisin, transmission
      electron microscopy observations revealed lysis of bacteria resulting from
      breakdown of the cell membrane. A time-killing curve showed a rapid bactericidal
      activity of nisin. Lastly, synergistic effects of nisin were observed in
      combination with several antibiotics, including penicillin, amoxicillin,
      tetracycline, streptomycin and ceftiofur. This study brought clear evidence
      supporting the potential of nisin for the prevention and treatment of S. suis
      infections in pigs.

PMID- 24096108
TI  - Step-by-step mechanism of DNA damage recognition by human 8-oxoguanine DNA
      glycosylase.
AB  - BACKGROUND: Extensive structural studies of human DNA glycosylase hOGG1 have
      revealed essential conformational changes of the enzyme. However, at present
      there is little information about the time scale of the rearrangements of the
      protein structure as well as the dynamic behavior of individual amino acids.
      METHODS: Using pre-steady-state kinetic analysis with Trp and 2-aminopurine
      fluorescence detection the conformational dynamics of hOGG1 wild-type (WT) and
      mutants Y203W, Y203A, H270W, F45W, F319W and K249Q as well as DNA-substrates was
      examined. RESULTS: The roles of catalytically important amino acids F45, Y203,
      K249, H270, and F319 in the hOGG1 enzymatic pathway and their involvement in the
      step-by-step mechanism of oxidative DNA lesion recognition and catalysis were
      elucidated. CONCLUSIONS: The results show that Tyr-203 participates in the
      initial steps of the lesion site recognition. The interaction of the His-270
      residue with the oxoG base plays a key role in the insertion of the damaged base
      into the active site. Lys-249 participates not only in the catalytic stages but
      also in the processes of local duplex distortion and flipping out of the oxoG
      residue. Non-damaged DNA does not form a stable complex with hOGG1, although a
      complex with a flipped out guanine base can be formed transiently. GENERAL
      SIGNIFICANCE: The kinetic data obtained in this study significantly improves our
      understanding of the molecular mechanism of lesion recognition by hOGG1.

PMID- 24096109
TI  - Histopathology predicts clinical outcome in advanced epithelial ovarian cancer
      patients treated with neoadjuvant chemotherapy and debulking surgery.
AB  - OBJECTIVE: To analyze the factors prognostic of survival in patients with
      advanced epithelial ovarian cancer (EOC) treated with neoadjuvant chemotherapy
      (NAC) followed by interval debulking surgery. METHODS: Outcomes were
      retrospectively in patients with advanced EOC or peritoneal cancer who received
      neoadjuvant paclitaxel and carboplatin chemotherapy every 3 weeks for three to
      four cycles, followed by interval debulking surgery and three additional cycles
      of the same regimens from January 2001 to November 2010. Therapeutic response was
      assessed histopathologically as grade 0 to 3, based on the degree of
      disappearance of cancer cells, displacement by necrotic and fibrotic tissue, and
      tumor-induced inflammation. Factors prognostic of progression-free survival (PFS)
      and overall survival (OS) were calculated. RESULTS: The 124 enrolled patients had
      a median age of 62 years (range, 35-79 years). Viable cancer cells were observed
      in specimens resected from 72 patients (58%) at interval debulking surgery after
      NAC. Multivariate analysis using the Cox proportional hazard model showed that
      advanced (stage IV) disease (hazard ratio [HR]=1.94, p=0.003), residual cancer at
      the end of surgery >=1cm (HR=3.78, p<0.001), and histological grade 0-1 (HR=1.65,
      p=0.03) were independent predictors of decreased OS. Grade 0-1 was also an
      independent predictor of increased risk of relapse within 6 months (odds
      ratio=8.42, p=0.003). CONCLUSIONS: Residual disease of >=1cm, advanced stage, and
      the presence of more viable disease in resected specimens are prognostic factors
      for survival in advanced EOC patients receiving NAC followed by interval
      debulking surgery.

PMID- 24096111
TI  - Pathological response on surgical samples is an independent prognostic variable
      for patients with Stage Ib2-IIb cervical cancer treated with neoadjuvant
      chemotherapy and radical hysterectomy: an Italian multicenter retrospective study
      (CTF Study).
AB  - OBJECTIVES: The purpose of this retrospective multicenter study was to correlate
      patterns of recurrences and clinical outcome of cervical cancer patients who
      underwent neoadjuvant chemotherapy [NACT] to surgery. METHODS: This study was
      conducted on 333 patients with FIGO stage Ib2-IIb cervical cancer who underwent
      NACT to surgery with pelvic lymphadenectomy. The median follow-up was 66.5 months
      (range, 8-212 months). Overall optimal response rate was the sum of complete and
      optimal partial response rates. RESULTS: An overall optimal response was obtained
      in 64 patients (19.2%). As for the 220 sub-optimal responders (66.1%), 127
      patients had negative nodes and negative parametria and/or surgical margins, 75
      patients had positive nodes with positive or negative parametria and/or surgical
      margins, and 18 patients had positive parametria and/or surgical margins with
      negative nodes. At the time of the present analysis, 79 (23.7%) of the 333
      patients had a recurrence after a median time of 14.9 months (range, 4.5-123
      months). Recurrent disease was pelvic in 50 (63.3%), extra-pelvic in 22 (27.9%),
      and both in 7 (8.8%). On multivariate analysis, pathological response to NACT was
      an independent prognostic variable for recurrence-free and overall survival.
      Patients who did not achieve an overall optimal response had a 2.757-fold higher
      risk of recurrence and a 5.413-fold higher risk of death than those who obtained
      an overall optimal response. CONCLUSIONS: Results appear to suggest that the
      chemo-surgical approach is an effective therapeutic option for patients with
      stage Ib2-IIb cervical cancer and that pathological response to NACT is the
      strongest prognostic factor for the outcome.

PMID- 24096110
TI  - Non-cancer life stressors contribute to impaired quality of life in ovarian
      cancer patients.
AB  - OBJECTIVES: Diagnosis and treatment for a life threatening illness such as cancer
      are known to be psychologically impactful. However, little is known about the
      influence that non-cancer life stressors have on the quality of life (QOL) of
      ovarian cancer patients. The goal of the present study was to examine
      associations between non-cancer life stressors and QOL in 123 women with invasive
      epithelial ovarian cancer who were followed prospectively and longitudinally for
      one year. METHODS: Mixed models for repeated measures were used to examine the
      relationship between life stressors and QOL pre-surgery and one year later, while
      adjusting for age, cancer stage, depressive symptoms, anxiety, and chemotherapy
      status (at one year). Prospective associations between QOL pre-surgery and one
      year QOL were also examined. RESULTS: Number and severity of life stressors were
      unrelated to QOL of participants before surgery. At one year, however,
      participants experiencing a greater number of life stressors reported poorer
      concurrent physical well-being (PWB) (p=0.015), functional well-being (FWB)
      (p<0.0001), social well-being (SWB) (p=0.0003), and total QOL (p<0.0001). Similar
      effects were found for life event severity. Finally, experiencing a greater
      number of life stressors pre-surgery predicted poorer overall QOL one year post
      diagnosis (p<0.0001). CONCLUSIONS: Non-cancer life stressors can substantially
      impact long-term QOL of ovarian cancer patients, adjusting for medical variables
      such as chemotherapy and cancer stage, thus highlighting the importance of
      evaluating the stress burden of patients in ongoing cancer care.

PMID- 24096112
TI  - Clinical risk factors of PEGylated liposomal doxorubicin induced palmar plantar
      erythrodysesthesia in recurrent ovarian cancer patients.
AB  - INTRODUCTION: Studies have shown that body composition, age, gender, changes in
      monocyte count and repeated dosing alter pharmacokinetic properties of PEGylated
      liposomal doxorubicin (PLD). However, limited information exists regarding the
      clinical risk factors of ovarian cancer patients who develop palmar plantar
      erythrodysesthesia (PPE) while receiving PLD for cancer recurrence. METHODS: We
      conducted a retrospective cohort analysis of consecutive patients with recurrent
      ovarian and primary peritoneal cancer who were treated with PLD from 2005 to
      2009. Clinical and pathologic data were abstracted from electronic medical
      records. Statistical analyses were performed using univariate and bivariate
      analyses, logistic regression, and log rank-tests. RESULTS: Twenty-three percent
      (31/133) of patients developed PPE. Age, body mass index (BMI), race, stage, and
      histology did not significantly differ between PPE and non-PPE patients. There
      was a possible trend for decreasing PPE with increasing body mass index (BMI)
      (24.5% of normal weight, 27.5% of overweight; 23.8% of obese class I; 13.3% of
      obese class II; and 0% of obese class III), though not statistically significant.
      The number of chemotherapy regimens prior to PLD, and the mean cycles of PLD
      received did not differ between patients with and without PPE. 77.4% of PPE cases
      occurred within the first 3 infusion cycles. PPE was not associated with time to
      progression. CONCLUSION: Nearly one-quarter of ovarian cancer patients receiving
      PLD will develop PPE. Further investigation of factors such as BMI associated
      with PPE may aid in patient selection for PLD, and future development of other
      nanoparticle and liposomal agents.

PMID- 24096113
TI  - Phase II study of bevacizumab and pemetrexed for recurrent or persistent
      epithelial ovarian, fallopian tube or primary peritoneal cancer.
AB  - OBJECTIVE: We aimed to evaluate the efficacy and safety of combination
      bevacizumab/pemetrexed for the treatment of recurrent epithelial ovarian cancer
      (EOC). METHODS: Platinum-sensitive or -resistant patients with recurrent or
      persistent EOC were eligible if they had received up to 2 prior chemotherapy
      regimens, including a platinum/taxane regimen without prior bevacizumab.
      Pemetrexed 500 mg/m(2) IV and bevacizumab 15 mg/kg IV were administered every 3
      weeks. The primary endpoint was 6-month progression-free survival (PFS); other
      endpoints included toxicities, PFS and overall survival (OS). RESULTS: Thirty
      four patients received a median of 7 treatment cycles (range, 2-26). Median
      follow-up was 25.7 months (range, 3.0-47.2). Six month progression-free survival
      (PFS) was 56% (95% CI: 38-71). The following response rates were documented (%;
      95% CI): 0 complete response, 14 partial responses (41%; 25-59), 18 stable
      disease (53%; 35-70) and 2 progressive disease (6%; 1-20). Median PFS was 7.9
      months (95% CI, 4.6-10.9), with a median OS of 25.7 months (95% CI, 15.4-29.8).
      Twenty-two patients (64.7%) had a platinum-free interval (PFI) of >6 months prior
      to enrollment. Grade 3-4 hematologic toxicities included neutropenia (50%),
      leukopenia (26%), thrombocytopenia (12%) and anemia (9%). Non-hematologic grade 3
      4 toxicities included metabolic (29%), constitutional (18%), pain (18%) and
      gastrointestinal (15%). Two patients developed hematologic malignancies within
      one year of treatment. CONCLUSIONS: Combination bevacizumab/pemetrexed is an
      active option for both platinum-sensitive and -resistant recurrent EOC. Further
      investigation of cost and novel toxicities associated with this regimen may be
      warranted.

PMID- 24096114
TI  - Reducing readmissions after robotic surgical management of endometrial cancer: a
      potential for improved quality care.
AB  - OBJECTIVE: To describe readmission patterns after robotic surgery for endometrial
      cancer and identify risk factors for readmission within 90 days of discharge.
      METHODS: Patients with endometrial cancer who underwent robotic surgical
      management at an academic institution from 2006 to 2010 were identified. Patient
      characteristics, intraoperative data, and postoperative complications were
      analyzed. Student's t-test and Fisher's exact test were used to compare patients
      readmitted within 90 days to those who were not. RESULTS: Three hundred ninety
      five patients were included. Thirty (7.6%) were readmitted within 90 days of
      surgical discharge. Length of stay greater than one day (40.0% vs. 23.0%, p=0.04)
      and postoperative complication (63.3% vs. 13.4%, p<0.01) were associated with
      readmission. The median interval to readmission was 9.5 days and median duration
      of subsequent hospitalization was 2.5 days. Fever (31.3%) and workup for vaginal
      drainage (25.0%) were the most common reasons for readmission. Only 2 of the 10
      patients readmitted with fever had culture-proven infection, and no patients
      readmitted for vaginal drainage had a confirmed urinary tract injury. Of the 30
      patients readmitted, 5 required a second operation - 3 for vaginal cuff
      dehiscence and 2 for port site hernia. CONCLUSIONS: Robotic surgery for
      endometrial cancer was associated with a 7.6% readmission rate. The most common
      reasons for readmission, fever and evaluation for urinary tract injury, were
      frequently not associated with severe illness. This supports additional education
      to consider raising the threshold for readmission by using more widespread
      outpatient evaluation for the potential complications of robotic endometrial
      cancer surgery.

PMID- 24096116
TI  - Six chitinases from oriental river prawn Macrobrachium nipponense: cDNA
      characterization, classification and mRNA expression during post-embryonic
      development and moulting cycle.
AB  - Chitinase plays crucial physiological roles in crustaceans, including the
      digestion of chitin-containing food, moulting and the defense of shrimp against
      viruses. However, in contrast to insect species, no genome-wide analysis has been
      carried out in crustacean species and cDNAs encoding chitinase and chitinase-like
      proteins have been characterized in relatively few species. In this study, we
      identified six chitinase genes in the oriental river prawn, Macrobrachium
      nipponense, according to the established expressed sequence tag (EST) information
      using Rapid Amplification of the cDNA Ends (RACE) technique and homology cloning.
      We assigned these genes to three different chitinase groupings, which were
      designated MnCht1A, 1B, 3A, 3B, 3C and 4. The domain organization analysis of the
      six MnCht proteins revealed that only MnCht3C and MnCht4 possessed full
      structure, while MnCht1A, 1B, 3A and 3B lacked the serine/threonine (S/T)-rich
      linker and chitin-binding domains (CBDs). Their expression in different tissues
      and different developmental stages suggested that all of them have a function in
      the digestion of chitinous foods, modification of gut peritrophic membrane and
      degradation of the chitin exoskeleton. Analysis of the stage-specific moulting
      cycle and different temperature stimulation provided further evidence that
      MnCht1A, 1B and 3B have pivotal roles in the moulting cycle, while MnCht 4 only
      assists in the moulting process. This study provides important information for
      further investigations on the functions of chitinase in M. nipponense and other
      crustaceans. 

PMID- 24096117
TI  - Population based nationwide study of hypospadias in Sweden, 1973 to 2009:
      incidence and risk factors.
AB  - PURPOSE: We studied the incidence of hypospadias in Sweden during a 40-year
      period to determine if changes were associated with known risk factors. MATERIALS
      AND METHODS: We analyzed prospective data from nationwide health care and
      demographic registers collected for all males (1,948,591 total) born in Sweden
      between 1973 and 2009. The incidence of hypospadias per 1,000 live-born boys was
      calculated as number of cases divided by total number of births yearly. The
      association between hypospadias and risk factors was estimated using logistic
      regression, expressed as odds ratios. RESULTS: The nationwide incidence of boys
      diagnosed with hypospadias was approximately 4.5 per 1,000 live-born boys until
      1990, increasing to 8 per 1,000 boys during the following decade. Mild and severe
      phenotypes comprised the increase. Boys born small for gestational age (OR 4.34),
      as a twin (OR 1.8), as a result of in vitro fertilization (OR 1.15), or with
      parents from Asia (OR 1.45) or continental Europe (OR 1.41) were at increased
      risk for hypospadias. Multivariate analyses revealed that changes in risk factors
      did not explain the increased incidence. However, a systematic change in the
      classification of the diagnosis in registers could not be ruled out. CONCLUSIONS:
      This nationwide study demonstrates an increased incidence of hypospadias
      diagnoses in Sweden from 1990 to 1999 that is not attributable to previously
      known risk factors. The increase includes mild and severe phenotypes, suggesting
      that shifts in the diagnostic criteria are not the underlying cause.

PMID- 24096118
TI  - Efficacy and safety of the coadministration of tadalafil once daily with
      finasteride for 6 months in men with lower urinary tract symptoms and prostatic
      enlargement secondary to benign prostatic hyperplasia.
AB  - PURPOSE: Medical treatment for men with lower urinary tract symptoms and
      prostatic enlargement secondary to benign prostatic hyperplasia is 5alpha
      reductase inhibitor monotherapy or coadministration with an alpha-blocker. We
      assessed the effects of tadalafil 5 mg coadministered with finasteride 5 mg
      during 26 weeks on lower urinary tract symptoms and sexual symptoms. MATERIALS
      AND METHODS: In an international, randomized, double-blind, parallel study of men
      45 years old or older who were 5alpha-reductase inhibitor naive and had an I-PSS
      (International Prostate Symptom Score) of 13 or greater and prostate volume 30 ml
      or greater, 350 were treated with placebo/finasteride and 345 received
      tadalafil/finasteride for 26 weeks. Changes in lower urinary tract symptoms
      secondary to benign prostatic hyperplasia were assessed with the I-PSS, erectile
      dysfunction improvements were assessed with the IIEF-EF (International Index of
      Erectile Function-Erectile Function) in sexually active men and safety was
      assessed by evaluating adverse events. RESULTS: Least squares mean changes from
      baseline in I-PSS after 4, 12 and 26 weeks of tadalafil/finasteride
      coadministration were -4.0, -5.2 and -5.5, respectively. Corresponding values for
      placebo/finasteride coadministration were -2.3, -3.8 and -4.5 (p <= 0.022 at all
      visits favoring tadalafil/finasteride coadministration). I-PSS subscores (storage
      and voiding) and quality of life index were also numerically improved with
      tadalafil/finasteride coadministration. Least squares mean changes from baseline
      in IIEF-EF with tadalafil/finasteride coadministration were 3.7 after 4 weeks,
      and 4.7 after 12 and 26 weeks. Corresponding values for placebo/finasteride
      coadministration were -1.1, 0.6 and -0.0 (p <0.001 at all visits favoring
      tadalafil/finasteride coadministration). Tadalafil/finasteride coadministration
      was well tolerated and most adverse events were mild/moderate. CONCLUSIONS: The
      coadministration of tadalafil/finasteride provides early improvement in lower
      urinary tract symptoms in men with benign prostatic hyperplasia and prostatic
      enlargement. Tadalafil/finasteride coadministration also improves erectile
      function in men who have comorbid erectile dysfunction.

PMID- 24096119
TI  - Economic impact of training and career decisions on urological surgery.
AB  - PURPOSE: Medical students and residents make career decisions at a relatively
      young age that have significant implications for their future income. While most
      of them attempt to estimate the impact of these decisions, there has been little
      effort to use economic principles to illustrate the impact of certain variables.
      MATERIALS AND METHODS: The economic concept of net present value was paired with
      available Medical Group Management Association and Association of American
      Medical Colleges income data to calculate the value of career earnings based on
      variations in the choice of specialty, an academic vs a private practice career
      path and fellowship choices for urology and other medical fields. RESULTS: Across
      all specialties academic careers were associated with lower career earnings than
      private practice. However, among surgical specialties the lowest difference in
      value between these 2 paths was for urologists at only $334,898. Fellowship
      analysis showed that training in pediatric urology was costly in forgone
      attending salary and it also showed a lower future income than nonfellowship
      trained counterparts. An additional year of residency training (6 vs 5 years)
      caused a $201,500 decrease in the value of career earnings. CONCLUSIONS: Choice
      of specialty has a dramatic impact on future earnings, as does the decision to
      pursue a fellowship or choose private vs academic practice. Additional years of
      training and forgone wages have a tremendous impact on monetary outcomes. There
      is also no guarantee that fellowship training will translate into a more
      financially valuable career. The differential in income between private practice
      and academics was lowest for urologists.

PMID- 24096120
TI  - Direct effects of tadalafil on lower urinary tract symptoms versus indirect
      effects mediated through erectile dysfunction symptom improvement: integrated
      data analyses from 4 placebo controlled clinical studies.
AB  - PURPOSE: Tadalafil has regulatory approval for the treatment of men with
      signs/symptoms of benign prostatic hyperplasia with and without erectile
      dysfunction. We assessed whether the effects of treatment with tadalafil for
      lower urinary tract symptoms/benign prostatic hyperplasia are independent of
      improvements in erectile dysfunction. MATERIALS AND METHODS: Four separate
      analyses used integrated data from 4 randomized, double-blind, placebo controlled
      studies in men with lower urinary tract symptoms/benign prostatic hyperplasia
      with and without erectile dysfunction to test whether total I-PSS (International
      Prostate Symptom Score) improvement was due to improvement in IIEF-EF
      (International Index of Erectile Function-Erectile Function domain score).
      Unidirectional and bidirectional path analysis models determined direct and
      indirect treatment effects mediated by improvements in lower urinary tract
      symptoms/benign prostatic hyperplasia and erectile dysfunction symptoms. RESULTS:
      A total of 1,496 men, of whom 77% had erectile dysfunction, received at least 1
      dose of tadalafil 5 mg once daily or placebo. The placebo adjusted treatment
      effect for men with erectile dysfunction was represented by a mean decrease of 
      2.3 (p <0.0001) in total I-PSS vs -2.2 (p = 0.0007) for men without erectile
      dysfunction. The correlation between change from baseline in total I-PSS and IIEF
      EF was weak (r(2) = 0.08, p <0.0001). The unidirectional path analysis model
      suggested that the total treatment effect on total I-PSS score improvement (2.25)
      was derived from a direct treatment effect of 1.57 (70%, p <0.001) and an
      indirect treatment effect of 0.67 (30% via IIEF-EF improvement, p <0.001).
      Bidirectional path analysis showed that total I-PSS improvement was largely
      attributed to direct (92.5%, p <0.001) vs indirect (7.5%, p = 0.32) treatment
      effects via IIEF-EF improvement. CONCLUSIONS: Regardless of the analytical
      approach, self-reported erectile dysfunction status did not appreciably influence
      tadalafil treatment response in men with lower urinary tract symptoms/benign
      prostatic hyperplasia, supporting the dual action of tadalafil on lower urinary
      tract symptoms/benign prostatic hyperplasia and erectile dysfunction.

PMID- 24096121
TI  - OpenArray profiling reveals no differential modulation of miRNA by positive and
      negative CD4+ T cell immunoselection.

PMID- 24096122
TI  - The orphan nuclear receptor Ear-2 (Nr2f6) is a novel negative regulator of T cell
      development.
AB  - We describe a novel role for the orphan nuclear receptor Ear-2 in regulating T
      cell development. Retrovirus-mediated overexpression of Ear-2 (EAR-2++) in a bone
      marrow (BM) transplantation assay resulted in limited T cell development and a
      greater than tenfold decrease in thymus size and cellularity relative to
      controls. Ear-2-transduced murine BM hematopoietic stem cells (HSCs) in OP9-DL1
      cultures showed a proliferation deficit during days 1-5 after induction of
      differentiation, which corresponded to increased expression of the cell cycle
      regulators p21 (cdkn1a) and p27 (cdkn1b), as well as increased expression of
      Hes1, Notch3, Egr1, and Scl (Tal1) and decreased expression of Gli1, Gfi-1,
      HoxA9, PU.1, Nrarp, and Tcf1. In addition, there was a block in differentiation
      at the DN4 to double-positive (DP) transition accompanied by an increase in
      apoptosis, similar to the deficit seen in the RORgammat null mouse. Gene
      expression profiling revealed that, like the RORgammat-deficient mouse, EAR-2++
      DP cells had decreased expression of BclXL and increased expression of the
      proapoptosis gene Bad. In addition, EAR-2++ DP cells had decreased expression of
      Bcl11b, PU.1, and HoxA9, and increased expression of Id2. Based on these
      findings, we conclude that EAR-2++ cells were able to migrate to, but not fully
      repopulate, the thymus because of a cell-intrinsic defect in the proliferation of
      DN1 cells followed by a block in differentiation from the DN4 to DP stage of T
      cell development. We conclude that Ear-2 is a novel negative regulator of T-cell
      development and that downregulation of Ear-2 is indispensable for the
      proliferation of DN1 cells and the survival of DN4-DP cells.

PMID- 24096123
TI  - Outcomes of autologous or allogeneic stem cell transplantation for non-Hodgkin
      lymphoma.
AB  - Transplant outcomes of autologous or allogeneic stem cell transplantation (SCT)
      have not been elucidated as a single cohort in non-Hodgkin lymphoma (NHL). We
      analyzed the outcomes of 270 adult recipients receiving autologous (auto) SCT (n
      = 198) or allogeneic (allo) SCT (n = 72) for NHL between the years 2000 and 2010.
      Five-year overall survival rates for B and T cell NHL were 58% and 50%,
      respectively (allo-SCT 51% vs. 54% for B and T-cell NHL, and auto-SCT 60% vs. 47%
      for B and T cell lymphoma, respectively). In multivariate analysis, the number of
      chemotherapy regimens and disease status pre-SCT were independently associated
      with long-term outcome after SCT (for both auto- and allo-SCT). We conclude that
      the type of transplantation offered to patients, based on patient selection and
      disease-related factors, can achieve long-term survival, highlighting the
      importance of further improvement in disease control and reducing procedure
      related mortality. The role of transplantation needs to be reevaluated in the era
      of targeted therapy.

PMID- 24096124
TI  - Glucocorticoids alter adrenomedullin receptor expression and secretion in
      endothelial-like cells and astrocytes.
AB  - Adrenomedullin (AM) is a novel vasodilatory peptide, which acts primarily through
      the calcitonin receptor-like receptor (CLR) in combination with either receptor
      activity-modifying-protein (RAMP) 2 or 3 (forming receptors, AM1 and AM2
      respectively). AM is also highly expressed in the brain and it has shown
      neuropeptide characteristics. Furthermore, AM plays an important role during
      inflammation. Interestingly, AM secretion and AM receptor expression had also
      proven to be glucocorticoid (GC)-dependent in a variety of cell types, suggesting
      an intriguing relationship between the two compounds that needed to be further
      characterized. Protein studies have never been carried out in endothelial cells
      and neither have astrocytes been thoroughly investigated. Hence we studied the
      effect of GC treatments on AM secretion and AM-sensitivity in ECV304 an
      endothelial-like cell line and C6 rat astrocytes, focusing on receptor protein
      expression. We demonstrated that GCs could directly up-regulate RAMP2 expression
      intracellularly in endothelial cells. On the contrary, GCs were essential to
      maintain RAMP basal levels in astrocytes, where they could alter AM secretion
      within 24h. Although RAMP2 has shown to be similarly up-regulated also by AM
      exposure, no change in AM receptor expression was noted in C6 cells. In
      conclusion, our study indicates that GCs are able to regulate AM-sensitivity and
      AM secretion differently in endothelial-like cells and astrocytes. In particular,
      GCs altered RAMP2 in ECV304 cells, while affecting AM secretion in astrocytes, an
      interaction which could have interesting therapeutic implications for the blood
      brain barrier regulation during both physiological and inflammatory conditions. 

PMID- 24096126
TI  - Comparison of functional near-infrared spectroscopy and electrodermal activity in
      assessing objective versus subjective risk during risky financial decisions.
AB  - Risk is an important factor impacting financial decisions. Risk can be processed
      objectively, e.g. as variance across possible outcomes of a choice option or
      subjectively, e.g. as value of that variance to a given individual. The aim of
      the present study was to test the potential of functional near-infrared
      spectroscopy (fNIRS) in assessing these different ways of processing risk while
      subjects decided between either high or low risk financial options or a safe
      (risk-free) option. For comparison we simultaneously measured electrodermal
      activity (EDA), a well-established method in decision-making research and a core
      measure of affective processes. FNIRS showed that lateral prefrontal cortex
      responses to high risk were enhanced relative to low risk only in risk-seeking
      individuals but reduced relative to low risk in risk-averse individuals. This is
      in-line with individual-specific risk processing reflecting the subjective value
      of risk. By contrast, EDA showed enhanced responses to high risk, independent of
      individual risk attitude, in-line with the notion of objective risk processing.
      The dissociation between the two measures arose even though they overall were
      equally sensitive to detect individual risk-related differences and even though
      there was an increased, risk attitude-independent, temporal coherence between the
      two measures during high-risk conditions. Our results suggest that hemodynamic
      responses in lateral prefrontal cortex as measured by fNIRS reflect the
      subjective value of risk, whereas EDA may index the objective amount of risk
      people are presented with. The findings suggest that fNIRS could be a useful
      method for studying risk behavior in financial decisions. 

PMID- 24096127
TI  - Test-retest reliability of structural brain networks from diffusion MRI.
AB  - Structural brain networks constructed from diffusion MRI (dMRI) and tractography
      have been demonstrated in healthy volunteers and more recently in various
      disorders affecting brain connectivity. However, few studies have addressed the
      reproducibility of the resulting networks. We measured the test-retest properties
      of such networks by varying several factors affecting network construction using
      ten healthy volunteers who underwent a dMRI protocol at 1.5T on two separate
      occasions. Each T1-weighted brain was parcellated into 84 regions-of-interest and
      network connections were identified using dMRI and two alternative tractography
      algorithms, two alternative seeding strategies, a white matter waypoint
      constraint and three alternative network weightings. In each case, four common
      graph-theoretic measures were obtained. Network properties were assessed both
      node-wise and per network in terms of the intraclass correlation coefficient
      (ICC) and by comparing within- and between-subject differences. Our findings
      suggest that test-retest performance was improved when: 1) seeding from white
      matter, rather than grey; and 2) using probabilistic tractography with a two
      fibre model and sufficient streamlines, rather than deterministic tensor
      tractography. In terms of network weighting, a measure of streamline density
      produced better test-retest performance than tract-averaged diffusion anisotropy,
      although it remains unclear which is a more accurate representation of the
      underlying connectivity. For the best performing configuration, the global within
      subject differences were between 3.2% and 11.9% with ICCs between 0.62 and 0.76.
      The mean nodal within-subject differences were between 5.2% and 24.2% with mean
      ICCs between 0.46 and 0.62. For 83.3% (70/84) of nodes, the within-subject
      differences were smaller than between-subject differences. Overall, these
      findings suggest that whilst current techniques produce networks capable of
      characterising the genuine between-subject differences in connectivity, future
      work must be undertaken to improve network reliability. 

PMID- 24096125
TI  - Sparse canonical correlation analysis relates network-level atrophy to
      multivariate cognitive measures in a neurodegenerative population.
AB  - This study establishes that sparse canonical correlation analysis (SCCAN)
      identifies generalizable, structural MRI-derived cortical networks that relate to
      five distinct categories of cognition. We obtain multivariate psychometrics from
      the domain-specific sub-scales of the Philadelphia Brief Assessment of Cognition
      (PBAC). By using a training and separate testing stage, we find that PBAC-defined
      cognitive domains of language, visuospatial functioning, episodic memory,
      executive control, and social functioning correlate with unique and distributed
      areas of gray matter (GM). In contrast, a parallel univariate framework fails to
      identify, from the training data, regions that are also significant in the left
      out test dataset. The cohort includes164 patients with Alzheimer's disease,
      behavioral-variant frontotemporal dementia, semantic variant primary progressive
      aphasia, non-fluent/agrammatic primary progressive aphasia, or corticobasal
      syndrome. The analysis is implemented with open-source software for which we
      provide examples in the text. In conclusion, we show that multivariate techniques
      identify biologically-plausible brain regions supporting specific cognitive
      domains. The findings are identified in training data and confirmed in test data.

PMID- 24096128
TI  - Mycoplasma, bacterial vaginosis-associated bacteria BVAB3, race, and risk of
      preterm birth in a high-risk cohort.
AB  - OBJECTIVE: Genital tract infection accounts for approximately 25-40% of all
      preterm births. We sought to assess the relationship between preterm birth and
      selected vaginal bacterial taxa associated with preterm birth either directly or
      through their association with bacterial vaginosis (BV). STUDY DESIGN: Vaginal
      fluid for Gram stain was collected between 17 and 22 weeks' gestation as part of
      a randomized trial of ultrasound-indicated cerclage for preterm birth prevention
      in women at high risk for recurrent spontaneous preterm birth. Bacterial
      deoxyribonucleic acid was extracted from the Gram stain slides and analyzed using
      quantitative polymerase chain reaction. RESULTS: Among the 499 participants,
      Mycoplasma was positively correlated with increased risk of preterm (risk ratio
      [RR], 1.83; 95% confidence interval [CI], 1.52-2.22) as was Mobiluncus (RR, 1.36;
      95% CI, 1.07-1.73) and Atopobium (RR, 1.44; 95% CI, 1.1-1.87). However, there
      were strong interactions between the race/ethnic group and the presence of these
      and other individual taxa on risk of preterm birth. By contrast, bacterial
      vaginosis-associated bacteria (BVAB)-3 was consistently associated with a
      reduction in the risk of preterm birth for all racial/ethnic groups (0.55; 95%
      CI, 0.39-0.78). CONCLUSION: BV is characterized by a reduction of Lactobacillus,
      and lactic acid-producing bacteria and the presence of Mobiluncus; we found these
      factors and the presence of Mycoplasma to be associated with an increased risk of
      preterm birth. By contrast, the presence of a recently identified organism
      sufficient to cause BV, BVAB3, decreased the risk of preterm birth. These
      findings give insight into why treating BV has mixed impact on risk of preterm
      birth.

PMID- 24096130
TI  - Exploring the effect of the ligand design on the interactions between [Ru(eta(5)
      C5H5)(PPh3)(N,O)][CF3SO3] complexes and human serum albumin.
AB  - Ruthenium complexes hold a great potential in chemotherapy as an alternative to
      the classical platinum based drugs. The organometallic compounds studied in the
      present work were previously found to exhibit important anticancer activities.
      Here we have investigated the binding of three ruthenium compounds, namely
      [Ru(eta(5)-C5H5)(PPh3)(bopy)][CF3SO3] 1, [Ru(eta(5)-C5H5)(PPh3)(2-ap)][CF3SO3] 2,
      and [Ru(eta(5)-C5H5)(PPh3)(isoquinpk)][CF3SO3] 3 (bopy=2-benzoylpyridine; 2-ap=2
      acetylpyridine; isoquinpk=1-isoquinolinyl phenyl ketone) to fatty acid human
      serum albumin (HSA) and fatty acid-free human serum albumin (HSA(faf)) at
      physiological pH7.4. The influence of the substituent groups on the
      heteroaromatic (N,O) coordinated ligand was also studied by fluorescence
      spectroscopy to get information about this binding. The Stern-Volmer quenching
      constants (KSV) were calculated at 293, 298 and 310K, with the corresponding
      thermodynamic parameters ?G, ?H and ?S as well. The fluorescence quenching method
      was used to determine the number of binding sites (n) and association constants
      (Ka) at the same temperatures. The binding site to HSA was confirmed by
      competitive studies of the ruthenium compounds with warfarin. 

PMID- 24096129
TI  - The functions of microRNAs and long non-coding RNAs in embryonic and induced
      pluripotent stem cells.
AB  - Embryonic stem cells (ESCs) and induced pluripotent stem cells (iPSCs) hold
      immense promise for regenerative medicine due to their abilities to self-renew
      and to differentiate into all cell types. This unique property is controlled by a
      complex interplay between transcriptional factors and epigenetic regulators.
      Recent research indicates that the epigenetic role of non-coding RNAs (ncRNAs) is
      an integral component of this regulatory network. This report will summarize
      findings that focus on two classes of regulatory ncRNAs, microRNAs (miRNAs) and
      long ncRNAs (lncRNAs), in the induction, maintenance and directed differentiation
      of ESCs and iPSCs. Manipulating these two important types of ncRNAs would be
      crucial to unlock the therapeutic and research potential of pluripotent stem
      cells. 

PMID- 24096131
TI  - Nanosilver cytotoxicity in rainbow trout (Oncorhynchus mykiss) erythrocytes and
      hepatocytes.
AB  - Silver nanoparticles (AgNPs) are present in a multitude of consumer and medical
      products; however, the toxicity of AgNPs is not fully understood. This research
      aimed to elucidate the relationship between AgNP cytotoxicity and oxidative
      stress and damage in rainbow trout (Oncorhynchus mykiss) hepatocytes and
      erythrocytes in comparison to silver ions (Ag(+)). Generally the cytotoxicity of
      AgNPs and Ag(+) was similar, such that both silver types generated reactive
      oxygen species, decreased glutathione levels, and decreased activities of
      glutathione reductase and glutathione-S-transferase. Nonetheless, the two silver
      types had different cellular targets; AgNPs increased lipid peroxidation without
      apparent uptake into the cells whereas Ag(+) increased DNA damage. Furthermore,
      the toxicity of both silver types was generally decreased in cells treated with
      cysteine while treatment with buthionine sulfoximine increased the toxicity of
      both silver types. 

PMID- 24096132
TI  - Direct and simple detection of recombinant proteins from cell lysates using
      differential scanning fluorimetry.
AB  - A simple, inexpensive, and universal method to quantify the recombinant proteins
      in Escherichia coli cell lysate using differential scanning fluorimetry (DSF) is
      reported. This method is based on the precise correlation between
      Delta(fluorescence intensity) determined by DSF and the amount of protein in
      solution. We first demonstrated the effectiveness of the DSF method using two
      commercially available enzymes, alpha-amylase and cellobiase, and then confirmed
      its utility with two recombinant proteins, amylosucrase and maltogenic amylase,
      expressed in E. coli. The Delta(fluorescence intensity) in DSF analysis
      accurately correlated with the concentration of the purified enzymes as well as
      the recombinant proteins in E. coli cell lysates. The main advantage of this
      method over other techniques such as Western blotting, enzyme-linked
      immunosorbent assay (ELISA), and green fluorescence protein (GFP) fusion proteins
      is that intact recombinant protein can be quantified without the requirement of
      additional chemicals or modifications of the recombinant protein. This DSF assay
      can be performed using widely available equipment such as a real-time polymerase
      chain reaction (RT-PCR) instrument, microplates or microtubes, and fluorescent
      dye. This simple but powerful method can be easily applied in a wide range of
      research areas that require quantification of expressed recombinant proteins. 

PMID- 24096133
TI  - Pursuing type 1 diabetes mellitus and related complications through urinary
      proteomics.
AB  - Diabetes mellitus is a chronic metabolic disease with multiple complications, and
      its successful management requires early diagnosis, to allow timely
      interventions. Here, we have comprehensively analyzed the proteome changes in
      urine of type 1 diabetic subjects with and without complications such as
      retinopathy and nephropathy. gel electrophoresis combined to liquid
      chromatography-tandem mass spectrometry (GeLC-MS/MS) analysis of midstream urine
      highlighted the mechanisms involved in disease pathogenesis as, for instance
      wound healing and blood coagulation in all diabetics or altered ganglioside
      metabolism in retinopathy, and also some urinary proteins with potential
      diagnosis value. From these, gelsolin and antithrombin-III appear as promising
      diagnosis markers for type 1 diabetes mellitus (T1DM), whereas ephrin type-B
      receptor 4 and vitamin K-dependent protein Z seem to be promising markers for
      advanced T1DM disease state presenting retinopathy and nephropathy (T1DM-R + N).
      Data also suggest urinary ganglioside GM2 activator and beta-hexosaminidase
      subunit beta as potential urinary markers of retinopathy in diabetics. Taken
      together, the present exploratory urinary proteomic analysis might be seen as an
      important starting point for studies targeting specific urinary proteins aimed at
      the implementation of new biomarkers for the early detection of T1DM-related
      microvascular complications. 

PMID- 24096134
TI  - N-Acetyl cysteine blunts proteotoxicity in a heat shock protein-dependent manner.
AB  - N-Acetyl cysteine, a glutathione precursor, has been shown to benefit patients
      with Alzheimer's disease and reduce the symptoms of traumatic brain injury in
      soldiers. Parkinson's and Alzheimer's disease are both characterized by stress
      from protein misfolding, or proteotoxicity. We have developed a high-throughput
      model of proteotoxicity by treating neuroblastoma N2a cells with the proteasome
      inhibitor MG132 and performing three independent assays for viability. Our
      previous study showed that N-acetyl cysteine protects N2a cells against two
      sequential treatments of MG132 and raises glutathione levels in a two-hit model
      of synergistic neurodegeneration. In the present study, however, N-acetyl
      cysteine was found to reduce the toxicity of a single hit of MG132 independent of
      its effect on glutathione. All three viability assays confirmed this protection.
      We measured heat shock protein 70 (Hsp70) levels because Hsp70 is a protective
      chaperone that helps refold proteins or guides ubiquitinated proteins toward
      degradation by the proteasome. Hsp70 levels were higher in MG132-treated cells
      when N-acetyl cysteine was applied. No parallel change in heat shock cognate 70
      (Hsc70) was elicited. Inhibition of Hsp70/Hsc70 activity with VER 155008
      attenuated the protection afforded by N-acetyl cysteine in a dose-responsive
      manner. MG132 induced a large rise in ubiquitinated proteins and N-acetyl
      cysteine reduced this effect. Consistent with the chaperone functions of Hsp70,
      VER 155008 also prevented the reduction in ubiquitin-conjugated proteins by N
      acetyl cysteine. These data reveal a new role for N-acetyl cysteine: this
      compound may reduce misfolded protein levels and ameliorate proteotoxicity
      through heat shock proteins. These findings broaden the potential mechanisms of
      action for this dietary supplement in neurodegenerative proteinopathies. 

PMID- 24096135
TI  - Reduction in heat shock protein 90 correlates to neuronal vulnerability in the
      rat piriform cortex following status epilepticus.
AB  - In the present study, we addressed the question of whether the distinct patterns
      of heat shock protein (HSP) 70 and HSP90 expressions in the brain region
      represents the regional specific responses to status epilepsticus (SE) in an
      effort to better understand the role of HSPs in epileptogenic insult. HSP70
      immunoreactivity was increased in CA3 pyramidal cells as well as dentate granule
      cells at 12h-1week after SE. HSP70 immunoreactivity was transiently increased in
      neurons within the piriform cortex (PC) following SE. Linear regression analysis
      showed no correlation between the intensity of NeuN and that of HSP70. In
      contrast to HSP70, HSP90 immunoreactivity was decreased in CA1-3 pyramidal cells
      at 4days-4weeks after SE. In addition, HSP90 immunoreactivity was decreased in PC
      neurons at 12h-4weeks after SE. linear regression analysis showed a direct
      proportional relationship between the intensity of NeuN and that of HSP90.
      Therefore, these findings suggest that HSP90 degradation may be closely related
      to neuronal vulnerability to SE insult. 

PMID- 24096137
TI  - Glutamate-induced epigenetic and morphological changes allow rat Muller cell
      dedifferentiation but not further acquisition of a photoreceptor phenotype.
AB  - Muller cells are not only the main glial cell type in the retina but also latent
      progenitor/stem cells, which in pathological conditions can transdifferentiate to
      a neuronal phenotype and regenerate the neurons lost in a mature retina. Several
      signal transduction pathways can induce the dedifferentiation of mature Muller
      cells to a progenitor-like state, including that stimulated by glutamate.
      However, the precise molecular mechanisms by which terminally differentiated
      cells are initially primed to acquire multipotency remain unclear. In the present
      study, we have characterized early genetic and epigenetic events that occur
      immediately after glutamate-induced dedifferentiation of fully differentiated
      Muller cells is initiated. Using Muller cell-enriched cultures from postnatal
      rats, we demonstrate that glutamate triggers a rapid dedifferentiation response
      characterized by changes in cell morphology coupled to the induction of
      progenitor cell marker gene expression (e.g., nestin, lin28 and sox2) within 1h.
      Dedifferentiation involved the activation of N-methyl-d-aspartate and type II
      metabotropic glutamate receptors, as well as global DNA demethylation (evident
      through the decrease in methyl-CpG-binding protein 2 immunoreactivity) and an
      increase in gadd45-beta gene expression; although, early progenitor gene
      expression was only partially inhibited by pharmacological impairment of DNA
      methylation. Importantly, the expression of Muller glia identity genes (i.e.,
      glutamine synthetase; cellular retinaldehyde binding protein, CRALBP) is retained
      through the process. Dedifferentiated Muller cells held an early neuronal
      differentiation potential similar to that observed in retinal progenitor-enriched
      cultures but, contrary to the latter, dedifferentiated Muller cells failed to
      further differentiate into mature photoreceptor lineages. We speculate that, in
      spite of the initial triggering of the dedifferentiation pathways, these cells
      may exhibit a certain degree of epigenetic memory that precludes them from
      further differentiation. 

PMID- 24096136
TI  - Gephyrin plays a key role in BDNF-dependent regulation of amygdala surface
      GABAARs.
AB  - Brain-derived neurotrophic factor (BDNF) is critically involved in synaptic
      plasticity and neurotransmission. Our lab has previously found that BDNF
      activation of neurotrophic tyrosine kinase, receptor, type 2 (TrkB) is required
      for fear memory formation and that GABAA receptor (GABAAR) subunits and the GABAA
      clustering protein gephyrin are dynamically regulated during fear memory
      consolidation. We hypothesize that TrkB-dependent internalization of GABAARs may
      partially underlie a transient period of amygdala hyperactivation during fear
      memory consolidation. We have previously reported that BDNF modulates GABAAR
      alpha1 subunit sequestration in cultured hippocampal and amygdala neurons by
      differential phosphorylation pathways. At present, no studies have investigated
      the regulation of gephyrin and GABAAR alpha1 subunits following BDNF activation
      in the amygdala. In this study, we confirm the association of GABAAR alpha1 and
      gamma2 subunits with gephyrin on mouse amygdala neurons by coimmunoprecipitation
      and immunocytochemistry. We then demonstrate that rapid BDNF treatment, as well
      as suppression of gephyrin protein levels on amygdala neurons, induced
      sequestration of surface alpha1 subunits. Further, we find that rapid exposure of
      BDNF to primary amygdala cultures produced decreases in gephyrin levels, whereas
      longer exposure resulted in an eventual increase. While total alpha1 subunit
      levels remained unchanged, gephyrin was downregulated in whole cell homogenates,
      but enhanced in complexes with GABAARs. Our data with anisomycin suggest that
      BDNF may rapidly induce gephyrin protein degradation, with subsequent gephyrin
      synthesis occurring. Together, these findings suggest that gephyrin may be a key
      factor in BDNF-dependent GABAAR regulation in the amygdala. This work may inform
      future studies aimed at elucidating the pathways connecting BDNF, GABAA systems,
      gephyrin, and their role in underlying amygdala-dependent learning. 

PMID- 24096138
TI  - An eight month randomized controlled exercise intervention alters resting state
      synchrony in overweight children.
AB  - Children with low aerobic fitness have altered brain function compared to higher
      fit children. This study examined the effect of an 8-month exercise intervention
      on resting state synchrony. Twenty-two sedentary, overweight (body mass index
      >=85th percentile) children 8-11 years old were randomly assigned to one of two
      after-school programs: aerobic exercise (n=13) or sedentary attention control
      (n=9). Before and after the 8-month programs, all subjects participated in
      resting state functional magnetic resonance imaging scans. Independent components
      analysis identified several networks, with four chosen for between-group
      analysis: salience, default mode, cognitive control, and motor networks. The
      default mode, cognitive control, and motor networks showed more spatial
      refinement over time in the exercise group compared to controls. The motor
      network showed increased synchrony in the exercise group with the right medial
      frontal gyrus compared to controls. Exercise behavior may enhance brain
      development in children.

PMID- 24096139
TI  - Treatment of acute schizophrenia with paliperidone ER: predictors for treatment
      response and benzodiazepine use.
AB  - The Paliperidone ER Treatment in Acute Intervention (PERTAIN) study was designed
      to explore treatment response, tolerability, and safety of flexible doses of
      paliperidone ER in patients with schizophrenia admitted for an acute
      exacerbation. This paper addresses a secondary analysis of PERTAIN data designed
      to explore predictors for treatment response, flexible dosing, and concomitant
      benzodiazepine use. This prospective, multicenter, phase 3b, open-label, single
      arm, 6-week study used flexible doses of paliperidone ER (3 to 12mg once daily)
      to treat patients hospitalized for an acute exacerbation of schizophrenia,
      reflecting more closely daily clinical practice. Predictive models were evaluated
      for paliperidone ER flexible dosing, treatment response, and concomitant
      treatment with benzodiazepines as distinct independent variables. For the
      analysis of explanatory variables, a stepwise logistic regression was used,
      taking into account patient age, gender, body mass index, diagnosis and duration
      of schizophrenia, number of prior hospitalizations, psychotic symptoms (PANSS),
      disease severity (CGI-S), and patient functioning (PSP) at baseline. Early
      response (defined as response within 2weeks of treatment initiation) was also
      used as a predictor. Clinical response (defined as >=30% decrease in PANSS total
      score and >=1 point decrease in CGI-S from baseline to endpoint) was predicted by
      early clinical response (p<0.001) and there was a trend for the diagnosis of
      paranoid schizophrenia vs. other types of schizophrenia to predict clinical
      response (p=0.0525). High response (defined as >=50% decrease in PANSS total
      score and >=2 points decrease in CGI-S from baseline to endpoint) was predicted
      by early high response, higher baseline CGI-S, or female gender. More severely
      ill patients with a higher baseline CGI-S were twice likely to be treated
      concomitantly with a benzodiazepine. 

PMID- 24096141
TI  - Steps/day and metabolic syndrome in African American adults: the Jackson Heart
      Study.
AB  - OBJECTIVE: To examine the relationship between pedometer-measured step count data
      and the Metabolic Syndrome (MetS) in African American adults. METHOD: 379 African
      American adults (mean age 60.1 years; 60% female) enrolled in the Jackson Heart
      Study (Jackson, MS) from 2000 to 2004 provided sufficient pedometer data for
      inclusion in this analysis. MetS was classified according to the International
      Diabetes Federation Task Force on Epidemiology and Prevention. RESULTS: Using
      steps/day categorized as tertiles (<3717 (referent), 3717-6238, >6238),
      participants taking 3717-6238 (Odds Ratio (OR)(95% Confidence Interval (CI))=0.34
      (0.19, 0.61)) and >6238 steps/day (OR(95% CI)=0.43 (0.23, 0.78)) had lower odds
      of having MetS compared to participants in the lowest tertile. Using previously
      suggested steps/day cut-points (<2500 (referent), 2500-4999, 5000-7499, >=7500),
      the odds of having MetS were lower for participants taking 2500-4999 (OR(95%
      CI)=0.32 (0.14, 0.72)), 5000-7499 (OR(95% CI)=0.22 (0.09, 0.53)), and >7500
      (OR(95% CI)=0.26 (0.11, 0.65)) steps/day compared to those taking <2500
      steps/day. CONCLUSION: Compared to lower levels, higher levels of steps/day are
      associated with a lower prevalence of MetS in this older African American
      population.

PMID- 24096140
TI  - Neighborhood walkable urban form and C-reactive protein.
AB  - BACKGROUND: Walkable urban form predicts physical activity and lower body mass
      index, which lower C-reactive protein (CRP). However, urban form is also related
      to pollution, noise, social and health behavior, crowding, and other stressors,
      which may complement or contravene walkability effects. PURPOSE: This paper
      assesses within-neighborhood correlation of CRP, and whether three features of
      walkable urban form (residential density, street connectivity, and land use mix)
      are associated with CRP levels. METHODS: CRP measures (n=610) and
      sociodemographic data come from the 2001-3 Chicago Community Adult Health Study,
      linked with objective built environment data. RESULTS: Within-neighborhood
      correlations of CRP are greater than those of related health measures. A one
      standard deviation increase in residential density predicts significantly higher
      log CRP (e.g. beta=0.11, p<.01) in Chicago, while a one standard deviation
      increase in land use mix predicts significantly lower CRP (e.g. beta=-0. 19,
      p<0.01). Street connectivity is unrelated to CRP in this highly walkable city.
      DISCUSSION: Results suggest that residential density may be a risk factor for
      inflammation, while greater walkability of mixed land use areas may be
      protective. It may be that negative aspects of density overcome the inflammatory
      benefits of walking.

PMID- 24096142
TI  - Treating symptomatic coronary artery disease in patients with Von Willebrand
      disease.
AB  - There is limited data on the occurrence of coronary artery disease (CAD) in
      patients with Von Willebrand disease and the literature is even scarce on their
      management. We at our institute reviewed the medical records of 198 patients with
      Von Willebrand disease over a period of 15years, of which 6 were found to have
      symptomatic CAD. Acute coronary syndrome was noted in 3 patients while the
      remaining 3 had stable angina. Cardiac catheterization showed that left main
      coronary artery was the culprit vessel in all of these patients. In terms of
      management, stents were placed in 3 patients, two of them underwent coronary
      artery bypass grafting, and the remaining one patient was medically managed.
      Aspirin, and in some patients clopidogrel, was well tolerated with minimal side
      effects. 

PMID- 24096143
TI  - Serine/threonine phosphatases regulate platelet alphaIIbbeta3 integrin receptor
      outside-in signaling mechanisms and clot retraction.
AB  - AIMS: We studied the role of serine/threonine phosphatases (PSTPs) on
      alphaIIbbeta3 signaling and the potential selectivity of the level of PSTP
      inhibition with okadaic acid (OA) on alphaIIbbeta3 signaling for regulation of
      platelet aggregation and clot retraction. MAIN METHODS: We used washed platelets
      from normal donors and OA as inhibitor of PSTPs. Clot retraction was induced by
      1U/mL of thrombin. Reorganized cytoskeleton was isolated from Triton X-100 lysed
      platelets. The presence of proteins incorporated to the cytoskeleton was assayed
      by immunoblotting with specific antibodies. KEY FINDINGS: We found that both 100
      and 500 nM OA blocked platelet mediated clot retraction. In contrast, only 500 nM
      OA inhibited thrombin-induced inside-out alphaIIbbeta3 activation, platelet
      aggregation, and cytoskeletal reorganization. Among markers of alphaIIbbeta3
      outside-in signaling, 500 nM OA inhibited the incorporation to the cytoskeleton
      of syk, src, and FAK (Focal Adhesion Kinase) tyrosine kinases and the
      incorporation and phosphorylation at Tyr(759) of the beta3 chain of
      alphaIIbbeta3, while 100 nM OA only inhibited the FAK translocation and its
      tyrosine phosphorylation. SIGNIFICANCE: The level of inhibition of PSTPs by low
      or high OA concentration (33% and 73% inhibition, respectively) in intact whole
      cells differentially regulates platelet aggregation and integrin signaling, but
      have a common effect in blocking clot retraction. The latter may be associated
      with the presence of phosphorylated FAK in the cytoskeleton. This study reveals a
      novel target for anti-platelet treatment to block clot retraction without
      affecting the platelet hemostatic function by a partial inhibition of PSTPs.

PMID- 24096144
TI  - Structural characterization and antioxidant activity of a low-molecular
      polysaccharide from Dendrobium huoshanense.
AB  - The present study aimed at investigating the structural features and antioxidant
      activities of a polysaccharide fraction (DHP1A) obtained from Dendrobium
      huoshanense, a precious herb medicine in China. DHP1A mainly consisted of mannose
      (Man), glucose (Glc) and a trace of galactose (Gal), with a molecular weight of
      6700Da. Its backbone contained (1->4)-linked alpha-D-Glcp, (1->6)-linked alpha-D
      Glcp and (1->4)-linked beta-D-Manp, with a branch of terminal beta-D-Galp. The in
      vitro antioxidant evaluation revealed that DHP1A had a remarkable inhibition
      effect on the FeCl2-induced lipid peroxidation. Furthermore, DHP1A pretreatment
      decreased the production of malondialdehyde (MDA), and restored the activities of
      superoxide dismutase (SOD), catalase (CAT) and glutathione peroxidase (GPx), as
      well as the level of glutathione (GSH) in the livers of CCl4-treated mice. These
      results suggested that DHP1A was a potential antioxidant component in D.
      huoshanense. 

PMID- 24096145
TI  - Biotransformation of 20(S)-protopanaxadiol by Aspergillus niger AS 3.1858.
AB  - The biotransformation of 20(S)-protopanaxadiol (1) by Aspergillus niger AS 3.1858
      was conducted. Seven metabolites 26-hydroxyl-20(S)-protopanaxadiol (2); 23, 24-en
      25-hydroxyl-20(S)-protopanaxadiol (3); 25, 26-en-20(S)-protopanaxadiol (4); (E)
      20, 22-en-25-hydroxyl-20(S)-protopanaxadiol (5); 25, 26-en-24(R)-hydroxyl-20(S)
      protopanaxadiol (6); 25, 26-en-24(S)-hydroxyl-20(S)-protopanaxadiol (7); and 23,
      24-en-25-ethoxyl-20(S)-protopanaxadiol (8) were afforded. Among them, 6, 7, and 8
      are new compounds. The chemical structures of these metabolites were elucidated
      based on extensive spectral data including 2D NMR and HRMS. In addition, the
      cytotoxicity of substrate and all transformed products was evaluated by MTT assay
      using a panel of seven human tumor cell lines (Du-145, Hela, K562, K562/ADR, SH
      SY5Y, HepG2, and MCF-7 cells) and one normal cell line Vero. 

PMID- 24096146
TI  - Purgative components in rhubarbs: adrenergic receptor inhibitors linked with
      glucose carriers.
AB  - Rhubarbs and their extractives have been used as cathartic for many years. There
      have been numerous breakthroughs in the pharmacological research of the drug.
      However, as the key point of the mechanism, the targets of the effective
      components still remain unclear. In this paper, with an in vitro system of
      isolated intestine, we found that both the rhubarb extractives and the
      anthraquinone derivatives can antagonize the adrenaline effectively. Furthermore,
      computer based docking provided the binding model of the anthraquinone
      derivatives and adrenergic receptor. Then, based on the results of the small
      intestinal promotion and purgative effect experiments in vivo, we built an
      "inhibitor-carrier" hypothesis to elucidate the mechanism of rhubarb. This work
      provided key massages for the pharmacological research of rhubarb, such a common
      and active medicinal plant, and might be of help for the development of new
      purgative drugs. 

PMID- 24096147
TI  - Hidden diversity in the Andes: comparison of species delimitation methods in
      montane marsupials.
AB  - Cryptic genetic diversity is a significant challenge for systematists faced with
      ever-increasing amounts of DNA sequence data. Computationally intensive
      coalescent-based analyses involving multiple unlinked loci are the only currently
      viable methods by which to assess the extent to which phenotypically similar
      populations (or metapopulations) are genetically distinct lineages. Although
      coalescent-based approaches have been tested extensively via simulations, few
      empirical studies have examined the impact of prior assumptions and dataset size
      on the ability to assess genetic isolation (evolutionary independence) using
      molecular data alone. Here, we consider the efficacy of two coalescent-based
      approaches (BPP and SpeDeSTEM) for testing the evolutionary independence of
      cryptic mtDNA haplogroups within three morphologically diagnosable species of
      Andean mouse opossums (Thylamys pallidior, T. sponsorius, and T. venustus).
      Fourteen anonymous nuclear loci, one X-linked nuclear intron, and one
      mitochondrial gene were analyzed for multiple individuals within each haplogroup
      of interest. We inferred individual gene trees for each locus and considered all
      of the nuclear loci jointly in a species-tree analysis. Using only the nuclear
      loci, we performed "species validation" tests for the cryptic mitochondrial
      lineages in SpeDeSTEM and BPP. For BPP, we also tested a wide range of prior
      assumptions, assessed performance of the rjMCMC algorithm, and examined how many
      loci were necessary to confidently delimit lineages. Results from BPP provided
      strong support for two independent evolutionary lineages each within T.
      pallidior, T. sponsorius, and T. venustus, whereas SpeDeSTEM results did not
      support splitting out mtDNA haplogroups as distinct evolutionary units. For most
      tests, BPP was robust to prior assumptions, although priors were shown to have an
      effect on both the strength of lineage recognition among T. venustus haplotypes
      and on the efficiency of the rjMCMC algorithm. Comparisons of results from
      datasets with different numbers of loci revealed that some cryptic lineages could
      be confidently delimited with as few as two loci. 

PMID- 24096149
TI  - Contribution of hydrophobic/hydrophilic modification on cationic chains of
      poly(epsilon-caprolactone)-graft-poly(dimethylamino ethylmethacrylate)
      amphiphilic co-polymer in gene delivery.
AB  - Nanoparticles (NPs) assembled from amphiphilic polycations have been certified as
      potential carriers for gene delivery. Structural modification of polycation
      moieties may be an efficient route to further enhance gene delivery efficiency.
      In this study two electroneutral monomers with different hydrophobicities, 2
      hydroxyethyl methacrylate (HEMA) and 2-hydroxyethyl acrylate (HEA), were
      incorporated into the cationic poly(dimethylamino ethyl methacrylate) (PDMAEMA)
      side-chains of amphiphilic poly(epsilon-caprolactone)-graft-poly(dimethylamino
      ethylmethacrylate) (PCD) by random co-polymerization, to obtain poly(epsilon
      caprolactone)-graft-poly(dimethylamino ethyl methacrylate-co-2-hydroxyethyl
      methacrylate) (PCD-HEMA) and poly(epsilon-caprolactone)-graft-poly(dimethylamino
      ethyl methacrylate-co-2-hydroxyethyl acrylate) (PCD-HEA). Minimal HEA or HEMA
      moieties in PDMAEMA do not lead to statistically significant changes in particle
      size, zeta potential, DNA condensation properties and buffering capacity of the
      naked NPs. However, the incorporation of HEMA and HEA lead to reductions and
      increases, respectively, in the surface hydrophilicity of the naked NPs and
      NPs/DNA complexes, which was confirmed by water contact angle assay. These simple
      modifications of PDMAEMA with HEA and HEMA moieties significantly affect the gene
      transfection efficiency on HeLa cells in vitro: PCD-HEMA NP/DNA complexes show a
      much higher transfection efficiency than PCD NPs/DNA complexes, while PCD-HEA
      NPs/DNA complexes show a lower transfection efficiency than PCD NP/DNA complexes.
      Fluorescence activated cell sorter and confocal laser scanning microscope results
      indicate that the incorporation of hydrophobic HEMA moieties facilitates an
      enhancement in both cellular uptake and endosomal/lysosomal escape, leading to a
      higher transfection efficiency. Moreover, the process of endosomal/lysosomal
      escape confirmed in our research that PCD and its derivatives do not just rely on
      the proton sponge mechanism, but also on membrane damage due to the polycation
      chains, especially hydrophobic modified ones. Hence, it is proved that
      hydrophobic modification of cationic side-chains is a crucial route to improve
      gene transfection mediated by polycation NPs.

PMID- 24096148
TI  - Review of mass spectrometry-based metabolomics in cancer research.
AB  - Metabolomics, the systematic investigation of all metabolites present within a
      biologic system, is used in biomarker development for many human diseases,
      including cancer. In this review, we investigate the current role of mass
      spectrometry-based metabolomics in cancer research. A literature review was
      carried out within the databases PubMed, Embase, and Web of Knowledge. We
      included 106 studies reporting on 21 different types of cancer in 7 different
      sample types. Metabolomics in cancer research is most often used for case-control
      comparisons. Secondary applications include translational areas, such as patient
      prognosis, therapy control and tumor classification, or grading. Metabolomics is
      at a developmental stage with respect to epidemiology, with the majority of
      studies including less than 100 patients. Standardization is required especially
      concerning sample preparation and data analysis. In the second part of this
      review, we reconstructed a metabolic network of patients with cancer by
      quantitatively extracting all reports of altered metabolites: Alterations in
      energy metabolism, membrane, and fatty acid synthesis emerged, with tryptophan
      levels changed most frequently in various cancers. Metabolomics has the potential
      to evolve into a standard tool for future applications in epidemiology and
      translational cancer research, but further, large-scale studies including
      prospective validation are needed.

PMID- 24096150
TI  - Effects of clodronate and alendronate on osteoclast and osteoblast co-cultures on
      silk-hydroxyapatite films.
AB  - The goal of this study was to explore the effects of osteoporosis-related
      therapeutics on bone remodeling in vitro. A previously established bone-tissue
      mimetic system consisting of silk protein biomaterials in combination with
      hydroxyapatite and human cells was used for the study. Silk-hydroxyapatite films
      were pre-complexed with the non-nitrogenous bisphosphonate clodronate or the
      nitrogenous bisphosphonate alendronate and cultured with THP-1 human acute
      monocytic leukemia cell line-derived osteoclasts, human mesenchymal stem cell
      derived osteoblasts or a direct co-culture of the two cell types. Metabolic
      activity, calcium deposition and alkaline phosphatase activity were assessed over
      12 weeks, and reconstructed remodeled biomaterial surfaces were also evaluated
      for quantitative morphological changes. Increased metabolic activity and
      increased roughness were found on the clodronate-complexed biomaterial substrates
      remodeled by osteoblasts and co-cultures of osteoblasts with osteoclasts, even at
      doses high enough to cause a 90% decrease in osteoclast metabolic activity. Films
      complexed with low doses of alendronate resulted in increased metabolic activity
      and calcium deposition by osteoblasts, while higher doses were similarly toxic
      among osteoclasts, osteoblasts and co-cultures. These results point to the
      utility of these well-defined bone-mimetic in vitro cultures as useful screens
      for therapeutics for bone-related diseases, particularly with the ability to
      conduct studies for extended duration (here for 12 weeks) and with pre-complexed
      drugs to mimic conditions found in vivo.

PMID- 24096151
TI  - Bioerodible system for sequential release of multiple drugs.
AB  - Because many complex physiological processes are controlled by multiple
      biomolecules, comprehensive treatment of certain disease conditions may be more
      effectively achieved by administration of more than one type of drug. Thus, the
      objective of the present research was to develop a multilayered, polymer-based
      system for sequential delivery of multiple drugs. The polymers used were
      cellulose acetate phthalate (CAP) complexed with Pluronic F-127 (P). After
      evaluating morphology of the resulting CAPP system, in vitro release of small
      molecule drugs and a model protein was studied from both single and multilayered
      devices. Drug release from single-layered CAPP films followed zero-order kinetics
      related to surface erosion of the association polymer. Release studies from
      multilayered CAPP devices showed the possibility of achieving intermittent
      release of one type of drug as well as sequential release of more than one type
      of drug. Mathematical modeling accurately predicted the release profiles for both
      single layer and multilayered devices. The present CAPP association polymer-based
      multilayer devices can be used for localized, sequential delivery of multiple
      drugs for the possible treatment of complex disease conditions, and perhaps for
      tissue engineering applications, that require delivery of more than one type of
      biomolecule. 

PMID- 24096152
TI  - Thiolated hyaluronan-based hydrogels crosslinked using oxidized glutathione: an
      injectable matrix designed for ophthalmic applications.
AB  - Future ophthalmic therapeutics will require the sustained delivery of bioactive
      proteins and nucleic acid-based macromolecules and/or provide a suitable
      microenvironment for the localization and sustenance of reparative progenitor
      cells after transplantation into or onto the eye. Water-rich hydrogels are ideal
      vehicles for such cargo, but few have all the qualities desired for novel
      ophthalmic use, namely in situ gelation speed, cytocompatibility,
      biocompatibility and capacity to functionalize. We describe here the development
      of an ophthalmic-compatible crosslinking system using oxidized glutathione
      (GSSG), a physiologically relevant molecule with a history of safe use in humans.
      When GSSG is used in conjunction with an existing hyaluronate-based, in situ
      crosslinkable hydrogel platform, gels form in less than 5 min using the thiol
      disulfide exchange reaction. This GSSG hydrogel supports the 3-D culture of
      adipose-derived stem cells in vitro and shows biocompatibility in preliminary
      intracutaneous and subconjunctival experiments in vivo. In addition, the thiol
      disulfide exchange reaction can also be used in conjunction with other thiol
      compatible chemistries to covalently link peptides for more complex formulations.
      These data suggest that this hydrogel could be well suited for local ocular
      delivery, focusing initially on front of the eye therapies. Subsequent uses of
      the hydrogel include delivery of back of the eye treatments and eventually into
      other soft, hyaluronan-rich tissues such as those from the liver and brain.

PMID- 24096153
TI  - Transcriptional profiles of Rel/NF-kappaB, inhibitor of NF-kappaB (IkappaB), and
      lipopolysaccharide-induced TNF-alpha factor (LITAF) in the lipopolysaccharide
      (LPS) and two Vibrio sp.-exposed intertidal copepod, Tigriopus japonicus.
AB  - The immune system and the role of immunity-related genes have rarely been studied
      in copepods, even though copepods have a primitive immune response system and
      also have a potential in pathogen transport higher trophic levels. In this study,
      we firstly cloned and characterized three core immune genes such as nuclear
      factor kappaB (NF-kappaB), inhibitor of NF-kappaB (IkappaB), and
      lipopolysaccharide-induced TNF-alpha factor (LITAF) genes in the intertidal
      copepod Tigriopus japonicus. Several in silico analyses based on conserved
      domains, motifs, and phylogenetic relationships were supporting their
      annotations. To investigate the immune-related role of three genes, we exposed
      lipopolysaccharide (LPS) and two Vibrio sp. to T. japonicus. After exposure of
      different concentrations of LPS and two Vibrio sp., transcripts of TJ-IkappaB and
      TJ-LITAF genes were significantly elevated during the time course in a dose
      dependent manner, while TJ-NF-kappaB transcripts were not significantly changed
      during exposure. These findings demonstrated that the copepod T. japonicus has a
      conserved immunity against infection.

PMID- 24096154
TI  - Cigarette smoke induces molecular responses in respiratory tissues of ApoE(-/-)
      mice that are progressively deactivated upon cessation.
AB  - Cigarette smoking is the primary etiology of chronic obstructive pulmonary
      disease (COPD) and a risk factor for both lung and cardiovascular (CV) diseases,
      which are rarely investigated concomitantly. Although smoking cessation shows
      clear CV risk benefit, lung-related disease risk remains higher in former smokers
      than in never smokers. We sought to determine the differential molecular
      responses of murine respiratory tissues to better understand the toxicity
      pathways involved in smoking-related disease risk and those related to the
      benefits of smoking cessation. ApoE(-/-) mice were exposed to mainstream
      cigarette smoke (CS) or a smoking cessation-mimicking protocol for up to 6 months
      and transcriptomics analysis of nasal epithelium and lung parenchyma performed.
      We supported our gene expression profiling approach with standard lung
      histopathology and bronchoalveolar lavage fluid (BALF) analysis. Many BALF
      analytes involved in functions ranging from inflammation to cell proliferation
      and tissue remodeling were found elevated in BALF. Gene expression levels of
      these molecules were also increased in lung tissue, suggesting that the
      inflammatory response was the result of local tissue activation and the
      contribution of recruited inflammatory cells. Gene set enrichment analysis (GSEA)
      of expression data from murine lungs and nasal epithelium showed distinct
      activation patterns of inflammation, complement, and xenobiotic metabolism
      pathways during CS exposure that were deactivated upon smoking cessation.
      Pathways involved in cell proliferation and tissue remodeling were activated by
      CS and progressively deactivated upon smoke exposure cessation. Differential CS
      mediated responses of pulmonary and nasal tissues reflect common mechanisms but
      also the varying degrees of epithelial functional specialization and exposure
      along the respiratory tract. 

PMID- 24096155
TI  - The DNT-EST: a predictive embryonic stem cell-based assay for developmental
      neurotoxicity testing in vitro.
AB  - As the developing brain is exquisitely vulnerable to chemical disturbances,
      testing for developmental neurotoxicity of a substance is an important aspect of
      characterizing its tissue specific toxicity. Mouse embryonic stem cells (mESCs)
      can be differentiated toward a neural phenotype, and this can be used as a model
      for early brain development. We developed a new in vitro assay using mESCs to
      predict adverse effects of chemicals and other compounds on neural development -
      the so-called DNT-EST. After treatment of differentiating stem cells for 48h or
      72h, at two key developmental stages endpoint for neural differentiation,
      viability, and proliferation were assessed. As a reference, we similarly treated
      undifferentiated stem cells 2 days after plating for 48h or 72h in parallel to
      the differentiating stem cells. Here, we show that chemical testing of a training
      set comprising nine substances (six substances of known developmental toxicity
      and three without specific developmental neurotoxicity) enabled a mathematical
      prediction model to be formulated that provided 100% predictivity and accuracy
      for the given substances, including in leave-one-out cross-validation. The
      described test method can be performed within two weeks, including data analysis,
      and provides a prediction of the developmental neurotoxicity potency of a
      substance. 

PMID- 24096156
TI  - Phosphoproteomic analysis of the striatum from pleiotrophin knockout and midkine
      knockout mice treated with cocaine reveals regulation of oxidative stress-related
      proteins potentially underlying cocaine-induced neurotoxicity and
      neurodegeneration.
AB  - The neurotrophic factors pleiotrophin (PTN) and midkine (MK) are highly
      upregulated in different brain areas relevant to drug addiction after
      administrations of different drugs of abuse, including psychostimulants. We have
      previously demonstrated that PTN and MK modulate amphetamine-induced
      neurotoxicity and that PTN prevents cocaine-induced cytotoxicity in NG108-15 and
      PC12 cells. In an effort to dissect the different mechanisms of action triggered
      by PTN and MK to exert their protective roles against psychostimulant
      neurotoxicity, we have now used a proteomic approach to study protein
      phosphorylation, in which we combined phosphoprotein enrichment, by immobilized
      metal affinity chromatography (IMAC), with two-dimensional gel electrophoresis
      and mass spectrometry, in order to identify the phosphoproteins regulated in the
      striatum of PTN knockout, MK knockout and wild type mice treated with a single
      dose of cocaine (15mg/kg, i.p.). We identified 7 differentially expressed
      phosphoproteins: 5'(3')-deoxyribonucleotidase, endoplasmic reticulum resident
      protein 60 (ERP60), peroxiredoxin-6 (PRDX6), glutamate dehydrogenase 1 (GLUD1),
      aconitase and two subunits of hemoglobin. Most of these proteins are related to
      neurodegeneration processes and oxidative stress and their variations specially
      affect the PTN knockout mice, suggesting a protective role of endogenous PTN
      against cocaine-induced neural alterations. Further studies are needed to
      validate these proteins as possible targets against neural alterations induced by
      cocaine. 

PMID- 24096157
TI  - Fish scale collagen sponge incorporated with Macrotyloma uniflorum plant extract
      as a possible wound/burn dressing material.
AB  - Application of plant extracts for the burn/wound treatment is followed over the
      decades as a common practice and it is an important aspect in clinical
      management. In this study porous collagen sponges (CS) were prepared using fish
      scales and were incorporated with mupirocin (CSM) and extracts of Macrotyloma
      uniflorum (CSPE) separately to impart antimicrobial activity to the sponges. The
      results showed that the addition of plant extract increased the tensile strength
      of CSPE and stability against collagenase enzyme. FTIR studies have shown the
      incorporation of plant extract in CSPE, SEM studies have revealed the porous
      nature of the sponges and XRD patterns have shown the retention of collagen
      triple helical structure even after the addition of plant extract. CSPE and CSM
      have exhibited antimicrobial properties. The sponges prepared were analysed for
      their in vitro biocompatibility studies using fibroblasts and keratinocyte cell
      lines and the results have shown their biocompatible nature. Based on the results
      obtained, CS, CSM and CSPE may be tried as a burn/wound dressing materials,
      initially, in small animals in vivo. 

PMID- 24096158
TI  - Controlled release of anticancer drug using graphene oxide as a drug-binding
      effector in konjac glucomannan/sodium alginate hydrogels.
AB  - In order to find new composite materials for the controlled release of drugs, a
      series of novel pH sensitive konjac glucomannan/sodium alginate (KGM/SA) and
      KGM/SA/graphene oxide (KGM/SA/GO) hydrogels were prepared, using GO as a drug
      binding effector for anticancer drug loading and release. The hydrogels were
      characterized using Fourier transform infrared spectroscopy (FTIR), and scanning
      electron microscopy (SEM). The effects of component ratio and pH on the swelling
      properties of hydrogels were studied. The release amount of 5-fluorouracil (5-FU)
      incorporated into KGM/SA/GO-3 hydrogels was about 38.02% at pH 1.2 and 84.19% at
      pH 6.8 after 6 h and 12 h, respectively. Therefore, the release rate of 5-FU from
      the functionalized KGM/SA using GO could be effectively controlled, Go has a
      great potential to be a promising drug-binding effector for hydrogel
      functionalization in drug delivery.

PMID- 24096159
TI  - CPT loaded nanoparticles based on beta-cyclodextrin-grafted poly(ethylene
      glycol)/poly (L-glutamic acid) diblock copolymer and their inclusion complexes
      with CPT.
AB  - This research is aimed to develop a nanoparticle delivery system based on beta
      cyclodextrin-grafted diblock copolymer and camptothecin (CPT) inclusion complexes
      with the purpose of enhancing the stability of CPT in aqueous media. Firstly,
      mPEG-PBLG diblock copolymer was synthesized by the ring-opening polymerization of
      gamma-benzyl-L-glutamate-N-carboxyanhydride (BLG-NCA) initiated with amine
      terminated poly (ethylene glycol) monomethyl ether (mPEG-NH2). After removal of
      benzyl groups, mono-6-amine-beta-cyclodextrin (EDA-beta-CD) units were coupled to
      the carboxyl groups of the copolymer as side groups to produce the host
      macromolecule mPEG-PLG(CD). The highly hydrophobic anticancer drug CPT was
      employed as the guest component which could be included into the host
      macromolecule to form supramolecular inclusion-complex mPEG-PLG(CPT@CD).
      Interestingly, the supramolecular complexes were able to form spherical
      nanoparticles with an average size of 98 nm in aqueous media confirmed by dynamic
      light scattering (DLS) and transmission electron microscopy (TEM), suggesting
      their passive targeting potential to tumor tissue. Due to the protection effect
      from a dual lock system (the environment of nanoparticles and the exterior
      surface of beta-CD), the active lactone ring of CPT showed remarkably enhanced
      stability against hydrolysis under physiological condition. The release profile
      of the mPEG-PLG(CPT@CD) nanoparticles in PBS buffer was found to be gradual and
      sustaining. It was worthy to note that the release could be accelerated by
      addition of adamantane carboxylate (ADC) as competitive guest compound,
      demonstrating the chemically stimulated release behavior of the nanoparticles.
      Compared with free CPT, the mPEG-PLG(CPT@CD) nanoparticles displayed essentially
      decreased cytotoxicity against MCF-7 cell line in 24 h because of a sustained
      release profile of CPT from the nanoparticles, moreover, the carrier mPEG-PLG(CD)
      itself showed almost no cytotoxicity, indicating its great potential as tumor
      tissue targeted drug delivery system.

PMID- 24096160
TI  - Elevated atherogenic index following oral administration of quaternized polyamine
      nanogels.
AB  - Quaternized polyamine nanogels possessing poly(ethylene glycol) (PEG)-tethered
      chains as the surface layer were prepared by redox-initiated emulsion
      polymerization of 2-(N,N-diethylamino)ethyl methacrylate (EAMA) in the presence
      of vinylbenzyl-ended poly(ethylene glycol) (PEG-CH2PhCHCH2), followed by
      quaternization with methyl iodide (QNG-I). QNG-I absorbed taurocholic acid
      regardless of environmental pH, because of the fixed positive charge of QNG-I.
      Oral administration of polyamine nanogels into mice tended to cause intestinal
      retention, with accumulation of up to 70% of the initial dose. Levels of low
      density lipoprotein cholesterol (LDL-C) in hyperlipidemic mice effectively
      decreased following oral administration of QNG-I. Interestingly, oral
      administration of QNG-I increased the levels of high-density lipoprotein
      cholesterol (HDL-C), resulting in an extremely high atherogenic index. Iodide
      counter-anions in QNG-I played an important role in the increase in HDL-C levels.

PMID- 24096161
TI  - Flavonoids from the leaves of Carya cathayensis Sarg. inhibit vascular
      endothelial growth factor-induced angiogenesis.
AB  - The total flavonoids (TFs) were isolated from the leaves of Carya cathayensis
      Sarg. (LCC), a well-known Chinese medicinal herb commercially cultivated in
      Tianmu Mountain district, a cross area of Zhejiang and Anhui provinces in China.
      Five flavonoids, i.e. cardamonin, pinostrobin chalcone (PC), wogonin, chrysin,
      and pinocembrin were the main components of the TFs. The TFs and these pure
      compounds suppressed vascular endothelial growth factor (VEGF)-induced
      angiogenesis as detected in the mouse aortic ring assay, and cardamonin showed
      the best effect among them. To further elucidate the mechanisms for suppressing
      angiogenesis of these flavonoids, assays of VEGF-induced proliferation and
      migration in human umbilical vein endothelial cells (HUVECs) were performed. The
      TFs, cardamonin, pinocembrin, and chrysin obviously suppressed both VEGF-induced
      HUVEC proliferation and migration. However, PC and wogonin not only slightly
      inhibited VEGF-induced proliferation but also remarkably suppressed those of
      migration in HUVECs. Our further study showed that cardamonin decreased the
      phosphorylation of ERK and AKT induced by VEGF with a dose-dependent manner in
      HUVECs. Our findings indicate that the TFs and these pure flavonoids may become
      potential preventive and/or therapeutic agents against angiogenesis-related
      diseases. 

PMID- 24096162
TI  - Assessment of diversity among populations of Rauvolfia serpentina Benth. Ex.
      Kurtz. from Southern Western Ghats of India, based on chemical profiling,
      horticultural traits and RAPD analysis.
AB  - Genetic, morphological and chemical variations of ten natural populations of
      Rauvolfia serpentina Benth. Ex. Kurtz. from Southern Western Ghats of India were
      assessed using RAPD markers reserpine content and morphological traits. An
      estimate of genetic diversity and differentiation between genotypes of breeding
      germplasm is of key importance for its improvement. Populations were collected
      from different geographical regions. Data obtained through three different
      methods were compared and the correlation among them was estimated. Statistical
      analysis showed significant differences for all horticultural characteristics
      among the accessions suggesting that selection for relevant characteristics could
      be possible. Variation in the content of Reserpine ranges from 0.192 g/100 g
      (population from Tusharagiri) to 1.312 g/100 g (population from Aryankavu). A
      high diversity within population and high genetic differentiation among them
      based on RAPDs were revealed caused both by habitat fragmentation of the low size
      of most populations and the low level of gene flow among them. The UPGMA
      dendrogram and PCA analysis based on reserpine content yielded higher separation
      among populations indicated specific adaptation of populations into clusters each
      of them including populations closed to their geographical origin. Genetic,
      chemical and morphological data were correlated based on Mantel test. Given the
      high differentiation among populations conservation strategies should take into
      account genetic diversity and chemical variation levels in relation to
      bioclimatic and geographic location of populations. Our results also indicate
      that RAPD approach along with horticultural analysis seemed to be best suited for
      assessing with high accuracy the genetic relationships among distinct R.
      serpentina accessions.

PMID- 24096163
TI  - Explaining the inconsistent associations of PR interval with mortality: the role
      of P-duration contribution to the length of PR interval.
AB  - BACKGROUND: There is a strong interest in PR interval as a predictor for adverse
      outcomes. However, inconsistent reports have emerged. OBJECTIVE: The purpose of
      this study was to test the hypothesis that the significance of PR interval as a
      predictor depends on the level of contribution of P duration to its length, a
      contribution that varies across populations. METHODS: We tested our hypothesis in
      7501 participants from the Third National Health and Nutrition Examination Survey
      (NHANES III). Participants were divided into two subgroups based on the median P
      duration contribution to PR interval (P duration/PR interval * 100). The risk of
      mortality associated with prolonged (>200 ms) and short (<120 ms) PR interval
      compared with normal PR interval was examined in all participants and each
      subgroup. RESULTS: P-duration contribution to the length of PR interval ranged
      from 30% to 90% (median 70%). During median follow-up of 13.8 years, 2541 deaths
      occurred. In a multivariable adjusted model, short but not prolonged PR interval
      was associated with mortality (hazard ratio [HR], (95% confidence interval [CI]):
      1.54 (1.18, 2.00) and 1.02 (0.90, 1.16), respectively). However, in a stratified
      analysis by P-duration contribution to PR interval, both short and prolonged PR
      interval were associated with mortality in participants with high P-duration
      contribution (HR (95% CI):1.46 (1.10, 1.94) and 2.00 (1.34, 2.99), respectively)
      but not in participants with low P-duration contribution (HR (95% CI):1.53 (0.68,
      3.41) and 0.99 (0.87, 1.13), respectively); interaction P = .008. CONCLUSION: PR
      interval associations with outcomes are dictated by the level of contribution of
      P duration to its length, a contribution that has a wide range and is expected to
      vary across populations. These findings could explain the inconsistent reports of
      PR-interval associations in different studies and call for caution when using PR
      interval in risk prediction models.

PMID- 24096164
TI  - Safe magnetic resonance imaging scanning of patients with cardiac rhythm devices:
      a role for computer modeling.
AB  - BACKGROUND: Although there are several hazards for patients with implanted
      pacemakers and defibrillators in the magnetic resonance imaging (MRI)
      environment, evaluation of lead electrode heating is the most complex because of
      the many influencing variables: patient size, anatomy, body composition, patient
      position in the bore, scan sequence (radiofrequency power level), lead routing,
      and lead design. Although clinical studies are an important step in demonstrating
      efficacy, demonstrating safety through clinical trials alone is not practical
      because of this complexity. OBJECTIVE: The purpose of this study was to develop a
      comprehensive modeling framework to predict the probability of pacing capture
      threshold (PCT) change due to lead electrode heating in the MRI environment and
      thus provide a robust safety evaluation. METHODS: The lead heating risk was
      assessed via PCT change because this parameter is the most clinically relevant
      measure of lead heating. The probability for PCT change was obtained by combining
      the prediction for power at the electrode-tissue interface obtained via
      simulations with a prediction for PCT change as a function of radiofrequency
      power obtained via an in vivo canine study. RESULTS: The human modeling framework
      predicted that the probability of a 0.5-V PCT change due to an MRI scan for the
      Medtronic CapSureFix MRI SureScan model 5086 MRI leads is <1/70,000 for chest
      scans and <1/10,000,000 for either head scans or lower torso scans. CONCLUSION:
      The framework efficiently models millions of combinations, delivering a robust
      evaluation of the lead electrode heating hazard. This modeling approach provides
      a comprehensive safety evaluation that is impossible to achieve using phantom
      testing, animal studies, or clinical trials alone.

PMID- 24096165
TI  - Multifocal Purkinje-like hamartoma and junctional ectopic tachycardia with a
      rapidly fatal outcome in a newborn.

PMID- 24096166
TI  - Magnetic resonance image intensity ratio, a normalized measure to enable
      interpatient comparability of left atrial fibrosis.
AB  - BACKGROUND: The measurement of late gadolinium-enhanced magnetic resonance
      imaging (LGE-MRI) intensity in arbitrary units limits the objectivity of
      thresholds for focal scar detection and interpatient comparisons of scar burden.
      OBJECTIVE: To develop and validate a normalized measure, the image intensity
      ratio (IIR), for the assessment of left atrial (LA) scar on LGE-MRI. METHODS:
      Electrocardiogram- and respiratory-gated 1.5 Tesla LGE-MRI was performed in 75
      patients (75% men; 62 +/- 8 years) before atrial fibrillation ablation. The local
      IIR was defined as LA myocardial signal intensity for each of the 20 sectors on
      contiguous axial image planes divided by the mean LA blood pool image intensity.
      Intracardiac point-by-point sampled electroanatomic map points were coregistered
      with the corresponding image sectors. RESULTS: The average bipolar voltage for
      all 8153 electroanatomic map points was 0.9 +/- 1.1 mV. In a mixed effects model
      accounting for within patient clustering, and adjusting for age, LA volume, mass,
      body mass index, sex, CHA2DS2-VASc score, atrial fibrillation type, history of
      previous ablations, and contrast delay time, each unit increase in local IIR was
      associated with 91.3% decrease in bipolar LA voltage (P < .001). Local IIR
      thresholds of >0.97 and >1.61 corresponded to bipolar voltage <0.5 and <0.1 mV,
      respectively. CONCLUSIONS: Normalization of LGE-MRI intensity by the mean blood
      pool intensity results in a metric that is closely associated with intracardiac
      voltage as a surrogate of atrial fibrosis.

PMID- 24096167
TI  - Successful ablation of macroreentrant left atrial tachycardia after pulmonary
      vein isolation in a patient with cor triatriatum.

PMID- 24096168
TI  - Mechanistic basis of excitation-contraction coupling in human pluripotent stem
      cell-derived ventricular cardiomyocytes revealed by Ca2+ spark characteristics:
      direct evidence of functional Ca2+-induced Ca2+ release.
AB  - BACKGROUND: Human embryonic stem cells (hESCs) serve as a potential unlimited ex
      vivo source of cardiomyocytes for disease modeling, cardiotoxicity screening,
      drug discovery, and cell-based therapies. Despite the fundamental importance of
      Ca(2+)-induced Ca(2+) release in excitation-contraction coupling, the mechanistic
      basis of Ca(2+) handling of hESC-derived ventricular cardiomyocytes (VCMs)
      remains elusive. OBJECTIVES: To study Ca(2+) sparks as unitary events of Ca(2+)
      handling for mechanistic insights. METHODS: To avoid ambiguities owing to the
      heterogeneous nature, we experimented with hESC-VCMs, purified on the basis of
      zeocin resistance and signature ventricular action potential after LV-MLC2v
      tdTomato-T2A-Zeo transduction. RESULTS: Ca(2+) sparks that were sensitive to
      inhibitors of sarco/endoplasmic reticulum Ca(2+)-ATPase (thapsigargin and
      cyclopiazonic acid) and ryanodine receptor (RyR; ryanodine, tetracaine) but not
      inositol trisphosphate receptors (xestospongin C and 2-aminoethyl
      diphenylborinate) could be recorded. In a permeabilization model, we further
      showed that RyRs could be sensitized by Ca(2+). Increasing external Ca(2+)
      dramatically escalated the basal Ca(2+) and spark frequency. Furthermore, RyR
      mediated Ca(2+) release sensitized nearby RyRs, leading to compound Ca(2+)
      sparks. Depolarization or L-type Ca(2+) channel agonist (FPL 64176 and Bay K8644)
      pretreatment induced an extracellular Ca(2+)-dependent cytosolic Ca(2+) increase
      and reduced the sarcoplasmic reticulum content. By contrast, removal of external
      Na(+) or the addition of the Na(+)-Ca(2+) exchanger inhibitor (KB-R7943 and SN-6)
      had no effect, suggesting that the Na(+)-Ca(2+) exchanger is not involved in
      triggering sparks. Inhibition of mitochondrial Ca(2+) uptake by carbonyl cyanide
      m-chlorophenyl hydrazone promoted Ca(2+) waves. CONCLUSION: Taken collectively,
      our findings provide the first lines of direct evidence that hESC-VCMs have
      functional Ca(2+)-induced Ca(2+) release. However, the sarcoplasmic reticulum is
      leaky and without a mature terminating mechanism in early development.

PMID- 24096169
TI  - Single nucleotide polymorphisms in arrhythmia genes modify the risk of cardiac
      events and sudden death in long QT syndrome.
AB  - BACKGROUND: Disease-modifying single nucleotide polymorphisms (SNPs) can help
      explain incomplete penetrance and variable expressivity in congenital long QT
      syndrome (LQTS) by altering susceptibility to arrhythmias. OBJECTIVE: The purpose
      of this study was to assess multiple arrhythmia SNPs (in 16 genes) in a distinct
      cohort of LQTS patients to identify modifier SNPs influencing the risk of sudden
      death. METHODS: This study included 273 patients with LQTS from the New Zealand
      Cardiac Inherited Disease Registry (154 long QT type 1, 96 long QT type 2, and 23
      long QT type 3), including 31 patients who had experienced death or resuscitated
      sudden cardiac death (RSCD). Patients were genotyped for 29 SNPs and tested for
      associations with clinical events and QTc length. Caucasian (n = 220) and Pacific
      Islander/New Zealand Maori (n = 53) ethnic groups were analyzed separately. This
      subgroup of Polynesian ancestry has not been previously studied for LQTS in
      either presentation or outcome. RESULTS: In Caucasians, four SNPs at two risk
      loci (NOS1AP: rs12143842 and rs16847548; and KCNQ1: rs10798 and rs8234) were
      significantly associated with clinical events after correction for multiple
      testing. Patients homozygous for the risk allele of rs12143842 had an increased
      risk of death/RSCD [hazard ratio 10.15, 95% confidence interval (2.38, 43.34), q
      = 0.045). Several other SNPs showed trends toward association with QTc length and
      clinical events. CONCLUSION: This study demonstrates that SNPs in NOS1AP and
      KCNQ1 are associated with an increased risk of cardiac events in LQTS patients,
      with the hazard ratio suggesting they have significant potential in clinical risk
      stratification.

PMID- 24096170
TI  - Novel utility of cryoablation for ventricular arrhythmias arising from the left
      aortic cusp near the left main coronary artery: a case series.
AB  - BACKGROUND: Ablation of ventricular tachycardia and premature ventricular
      contraction arising at the aortic root has been described. The use of
      radiofrequency ablation energy has been associated with life-threatening
      collateral damage. The use of cryoablation as a safer alternative energy source
      at the aortic root has not been previously described. OBJECTIVE: To demonstrate
      that cautious cryoablation near the ostia of the left main coronary artery is
      technically feasible and is a safe, effective alternative energy source for
      ablation at the aortic root. METHODS: Six patients (mean age 36 years; 4 women)
      with refractory frequent premature ventricular contractions or ventricular
      tachycardia underwent electrophysiological study and ablation. Two patients had
      associated nonischemic cardiomyopathy. Patients' ventricular arrhythmias were
      localized by using 3D mapping, with arrhythmia foci being mapped to the left
      aortic cusp near the left main coronary artery. The proximity to the ostium of
      the left main coronary artery was confirmed by using intracardiac ultrasound and
      coronary angiogram. Focal ablation, up to 240 seconds with freeze-thaw-freeze
      cycles, was performed by using an 8-mm cryoablation catheter via a retrograde
      aortic approach. RESULTS: Termination of ventricular arrhythmia during ablation
      was observed in all 6 patients. All patients were followed for greater than 6
      month postablation. One patient had acute ST-segment elevation during ablation
      below the left main ostium that resolved within 30 seconds of termination of
      ablation. There were no postprocedure complications and no significant arrhythmia
      recurrences. CONCLUSIONS: Aortic root ventricular arrhythmia ablation carries an
      increased risk for collateral damages. This case series demonstrates that
      cautious cryoablation near the ostia of the left main coronary artery can be
      performed and is a safe, effective alternative energy source for ablation at the
      aortic root.

PMID- 24096171
TI  - FGF12 is a candidate Brugada syndrome locus.
AB  - BACKGROUND: Less than 30% of the cases of Brugada syndrome (BrS) have an
      identified genetic cause. Of the known BrS-susceptibility genes, loss-of-function
      mutations in SCN5A or CACNA1C and their auxiliary subunits are most common. On
      the basis of the recent demonstration that fibroblast growth factor (FGF)
      homologous factors (FHFs; FGF11-FGF14) regulate cardiac Na(+) and Ca(2+) channel
      currents, we hypothesized that FHFs are candidate BrS loci. OBJECTIVE: The goal
      of this study was to test whether FGF12 is a candidate BrS locus. METHODS: We
      used quantitative polymerase chain reaction to identify the major FHF expressed
      in the human ventricle and then queried a phenotype-positive, genotype-negative
      BrS biorepository for FHF mutations associated with BrS. We queried the effects
      of an identified mutant with biochemical analyses combined with
      electrophysiological assessment. We designed a novel rat ventricular
      cardiomyocyte system in which we swapped the endogenous FHF with the identified
      mutant and defined its effects on multiple ionic currents in their native milieu
      and on the cardiac action potential. RESULTS: We identified FGF12 as the major
      FHF expressed in the human ventricle. In 102 individuals in the biorepository, we
      identified a single missense mutation in FGF12-B (Q7R-FGF12). The mutant reduced
      binding to the NaV1.5 C terminus, but not to junctophilin-2. In adult rat cardiac
      myocytes, Q7R-FGF12, but not wild-type FGF12, reduced Na(+) channel current
      density and availability without affecting Ca(2+) channel function. Furthermore,
      the mutant, but not wild-type FGF12, reduced action potential amplitude, which is
      consistent with a mutant-induced loss of Na(+) channel function. CONCLUSIONS:
      These multilevel investigations strongly suggest that Q7R-FGF12 is a disease
      associated BrS mutation. Moreover, these data suggest for the first time that FHF
      effects on Na(+) and Ca(2+) channels are separable. Most significantly, this
      study establishes a new method to analyze effects of human arrhythmogenic
      mutations on cardiac ionic currents.

PMID- 24096173
TI  - Ursodeoxycholic and deoxycholic acids: A good and a bad bile acid for intestinal
      calcium absorption.
AB  - The aim of this study was to investigate the effect of ursodeoxycholic acid
      (UDCA) on intestinal Ca(2+) absorption and to find out whether the inhibition of
      this process caused by NaDOC could be prevented by UDCA. Chicks were employed and
      divided into four groups: (a) controls, (b) treated with 10mM NaDOC, (c) treated
      with 60 MUg UDCA/100g of b.w., and (d) treated with 10mM NaDOC and 60 MUg
      UDCA/100g of b.w. UDCA enhanced intestinal Ca(2+) absorption, which was time and
      dose-dependent. UDCA avoided the inhibition of intestinal Ca(2+) absorption
      caused by NaDOC. Both bile acids altered protein and gene expression of molecules
      involved in the transcellular pathway of intestinal Ca(2+) absorption, but in the
      opposite way. UDCA aborted the oxidative stress produced by NaDOC in the
      intestine. UDCA and UDCA plus NaDOC increased vitamin D receptor protein
      expression. In conclusion, UDCA is a beneficial bile acid for intestinal Ca(2+)
      absorption. Contrarily, NaDOC inhibits the intestinal cation absorption through
      triggering oxidative stress. The use of UDCA in patients with cholestasis would
      be benefited because of the protective effect on the intestinal Ca(2+)
      absorption, avoiding the inhibition caused by hydrophobic bile acids and
      neutralizing the oxidative stress.

PMID- 24096172
TI  - Structure, mechanism, and dynamics of UDP-galactopyranose mutase.
AB  - The flavoenzyme UDP-galactopyranose mutase (UGM) is a key enzyme in
      galactofuranose biosynthesis. The enzyme catalyzes the 6-to-5 ring contraction of
      UDP-galactopyranose to UDP-galactofuranose. Galactofuranose is absent in humans
      yet is an essential component of bacterial and fungal cell walls and a cell
      surface virulence factor in protozoan parasites. Thus, inhibition of
      galactofuranose biosynthesis is a valid strategy for developing new
      antimicrobials. UGM is an excellent target in this effort because the product of
      the UGM reaction represents the first appearance of galactofuranose in the
      biosynthetic pathway. The UGM reaction is redox neutral, which is atypical for
      flavoenzymes, motivating intense examination of the chemical mechanism and
      structural features that tune the flavin for its unique role in catalysis. These
      studies show that the flavin functions as nucleophile, forming a flavin-sugar
      adduct that facilitates galactose-ring opening and contraction. The 3-dimensional
      fold is novel and conserved among all UGMs, however the larger eukaryotic enzymes
      have additional secondary structure elements that lead to significant differences
      in quaternary structure, substrate conformation, and conformational flexibility.
      Here we present a comprehensive review of UGM three-dimensional structure,
      provide an update on recent developments in understanding the mechanism of the
      enzyme, and summarize computational studies of active site flexibility. 

PMID- 24096174
TI  - Agency in the sensorimotor system and its relation to explicit action awareness.
AB  - People generally have a strong and immediate intuition whether they are the
      author of an action or not. Nevertheless, recent psychological studies focused on
      situations of ambiguous agency. These studies concluded that agency is an
      inference rather than a direct perception, and is, at least sometimes, illusory.
      Moreover, shared representations of executed and merely observed actions within
      the sensorimotor system pose a challenge to the idea that a sense of agency can
      be grounded within that system. Here, we sought to investigate whether the human
      motor system is indeed sensitive to whether observed actions are linked to agency
      or not. In addition, we investigated whether the mere observation of an action
      has comparable effects on low-level, sensorimotor measures of agency, and on high
      level, explicit representations of agency. To this end, we instructed
      participants to make simple manual movements, and manipulated the temporal
      correspondence between the movement that they made and the movement that they
      observed. Motor-evoked potentials to single-pulse TMS were taken as a low-level,
      sensorimotor measure of agency. To assess explicit representations of agency,
      participants verbally judged whether or not the observed movement temporally
      corresponded to the movement they executed. The results showed that corticospinal
      excitability varied with the degree of temporal correspondence of the executed
      and observed movements. Moreover, explicit agency judgments could be predicted
      from corticospinal excitability. This suggests that explicit judgments of agency
      could be directly based on information within the sensorimotor system. 

PMID- 24096175
TI  - Learning to detect but not to grasp suppressed visual stimuli.
AB  - A central implication of the two-visual-systems hypothesis (TVSH) is that the
      dorsal visuomotor system (vision-for-action) can make use of invisible
      information, whereas the ventral system (vision-for-perception) cannot (Milner &
      Goodale, 1995). Therefore, actions such as grasping movements should be
      influenced by invisible information while conscious reports remain unaffected. To
      test this assumption, we used a dichoptic stimulation technique--continuous flash
      suppression (CFS)--which has the potency to render stimuli invisible for up to
      seconds (Tsuchiya & Koch, 2005). In two experiments using CFS, participants were
      asked to grasp for invisible bars of different sizes (Experiment 1) or
      orientations (Experiment 2), or to report both measures verbally. Target
      visibility was measured trial-by-trial using the perceptual awareness scale
      (PAS). We found no evidence for the use of invisible information by the
      visuomotor system despite extensive training (600 trials) and the availability of
      haptic feedback. Participants neither learned to scale their maximum grip
      aperture to the size of the invisible stimulus, nor to align their hand to its
      orientation. Careful control of stimulus visibility across training sessions,
      however, revealed a robust tendency towards decreasing perceptual thresholds
      under CFS. We discuss our results within the framework of the TVSH and with
      respect to alternative models which emphasize the close functional interaction
      between the dorsal and ventral visual systems.

PMID- 24096177
TI  - Contribution of genetic and epigenetic mechanisms to Wnt pathway activity in
      prevalent skeletal disorders.
AB  - We reported previously that the expression of Wnt-related genes is lower in
      osteoporotic hip fractures than in osteoarthritis. We aimed to confirm those
      results by analyzing beta-catenin levels and explored potential genetic and
      epigenetic mechanisms involved. beta-Catenin gene expression and nuclear levels
      were analyzed by real time PCR and confocal immunofluorescence. Increased nuclear
      beta-catenin was found in osteoblasts isolated from patients with osteoarthritis
      (99 +/- 4 units vs. 76 +/- 12, p=0.01, n=10), without differences in gene
      transcription, which is consistent with a post-translational down-regulation of
      beta-catenin and decreased Wnt pathway activity. Twenty four single nucleotide
      polymorphisms (SNPs) of genes showing differential expression between fractures
      and osteoarthritis (WNT4, WNT10A, WNT16 and SFRP1) were analyzed in DNA isolated
      from blood of 853 patients. The genotypic frequencies were similar in both groups
      of patients, with no significant differences. Methylation of Wnt pathway genes
      was analyzed in bone tissue samples (15 with fractures and 15 with
      osteoarthritis) by interrogating a CpG-based methylation array. Six genes showed
      significant methylation differences between both groups of patients: FZD10,
      TBL1X, CSNK1E, WNT8A, CSNK1A1L and SFRP4. The DNA demethylating agent 5
      deoxycytidine up-regulated 8 genes, including FZD10, in an osteoblast-like cell
      line, whereas it down-regulated other 16 genes. In conclusion, Wnt activity is
      reduced in patients with hip fractures, in comparison with those with
      osteoarthritis. It does not appear to be related to differences in the allele
      frequencies of the Wnt genes studied. On the other hand, methylation differences
      between both groups could contribute to explain the differences in Wnt activity.

PMID- 24096176
TI  - A common nonsense mutation of the BLM gene and prostate cancer risk and survival.
AB  - BACKGROUND: Germline mutations of BRCA2 and NBS1 genes cause inherited recessive
      chromosomal instability syndromes and predispose to prostate cancer of poor
      prognosis. Mutations of the BLM gene cause another chromosomal instability
      clinical syndrome, called Bloom syndrome. Recently, a recurrent truncating
      mutation of BLM (Q548X) has been associated with a 6-fold increased risk of
      breast cancer in Russia, Belarus and Ukraine, but its role in prostate cancer
      etiology and survival has not been investigated yet. METHODS: To establish
      whether the Q548X allele of the BLM gene is present in Poland, and whether this
      allele predisposes to poor prognosis prostate cancer, we genotyped 3337 men with
      prostate cancer and 2604 controls. RESULTS: Q548X was detected in 13 of 3337
      (0.4%) men with prostate cancer compared to 15 of 2604 (0.6%) controls (OR=0.7;
      95% CI 0.3-1.4). A positive family history of any cancer in a first- or second
      degree relative was seen only in 4 of the 13 (30%) mutation positive families,
      compared to 49% (1485/3001) of the non-carrier families (p=0.3). The mean follow
      up was 49months. Survival was similar among carriers of Q548X and non-carriers
      (HR=1.1; p=0.9). The 5-year survival for men with a BLM mutation was 83%,
      compared to 72% for mutation-negative cases. CONCLUSIONS: BLM Q548X is a common
      founder mutation in Poland. We found no evidence that this mutation predisposes
      one to prostate cancer or affect prostate cancer survival. However, based on the
      observed 0.6% population frequency of the Q548X allele, we estimate that one in
      100,000 children should be affected by Bloom syndrome in Poland.

PMID- 24096178
TI  - Scaffold-assisted cartilage tissue engineering using infant chondrocytes from
      human hip cartilage.
AB  - OBJECTIVE: Studies about cartilage repair in the hip and infant chondrocytes are
      rare. The aim of our study was to evaluate the use of infant articular hip
      chondrocytes for tissue engineering of scaffold-assisted cartilage grafts.
      METHOD: Hip cartilage was obtained from five human donors (age 1-10 years).
      Expanded chondrocytes were cultured in polyglycolic acid (PGA)-fibrin scaffolds.
      De- and re-differentiation of chondrocytes were assessed by histological staining
      and gene expression analysis of typical chondrocytic marker genes. In vivo,
      cartilage matrix formation was assessed by histology after subcutaneous
      transplantation of chondrocyte-seeded PGA-fibrin scaffolds in immunocompromised
      mice. RESULTS: The donor tissue was heterogenous showing differentiated articular
      cartilage and non-differentiated tissue and considerable expression of type I and
      II collagens. Gene expression analysis showed repression of typical chondrocyte
      and/or mesenchymal marker genes during cell expansion, while markers were re
      induced when expanded cells were cultured in PGA-fibrin scaffolds. Cartilage
      formation after subcutaneous transplantation of chondrocyte loaded PGA-fibrin
      scaffolds in nude mice was variable, with grafts showing resorption and host cell
      infiltration or formation of hyaline cartilage rich in type II collagen. Addition
      of human platelet rich plasma (PRP) to cartilage grafts resulted robustly in
      formation of hyaline-like cartilage that showed type II collagen and regions with
      type X collagen. CONCLUSION: These results suggest that culture of expanded
      and/or de-differentiated infant hip cartilage cells in PGA-fibrin scaffolds
      initiates chondrocyte re-differentiation. The heterogenous donor tissue
      containing immature chondrocytes bears the risk of cartilage repair failure in
      vivo, which may be possibly overcome by the addition of PRP.

PMID- 24096179
TI  - The "anathema" of arbitrary categorization of continuous predictors.
AB  - In medicine in general, and in obstetrics in particular, it is common practice to
      use arbitrary cutoffs in expressing continuous variables. However, the dichotomy
      of continuous data is associated with loss of statistical power, which may result
      in inaccurate estimates in clinical prognosis or prediction of outcomes and,
      consequently, may lead to incorrect inferences. If the predictor is a continuous
      variable, arbitrary percentile-based categorizations without clinical
      justification is an anathema (Greek word meaning "curse") and should be
      discouraged. Instead, the clinical outcome of interest should be defined first
      and then a receiver operating characteristic curve analysis or other appropriate
      statistical techniques should be employed to determine the most optimal cutoff of
      the predictor. The next step should be to validate the cutoff in a different
      population before introducing it to clinical use or interventional trials. 

PMID- 24096180
TI  - Effectiveness of hospital-based postpartum procedures on pertussis vaccination
      among postpartum women.
AB  - OBJECTIVE: Pertussis causes significant morbidity among adults, children, and
      especially infants. Since 2006, pertussis vaccination has been recommended for
      women after delivery. We conducted a prospective, controlled evaluation of in
      hospital postpartum pertussis vaccination of birth mothers from October 2009
      through July 2010 to evaluate the effectiveness of hospital-based procedures in
      increasing postpartum vaccination. STUDY DESIGN: The intervention and comparison
      hospitals are private community facilities, each with 2000-6000 births/year. At
      the intervention hospital, physician opt-in orders for tetanus toxoid, reduced
      diphtheria toxoid and acellular pertussis vaccine (Tdap) before discharge were
      implemented in November 2009, followed by standing orders in February 2010. The
      comparison hospital maintained standard practice. Randomly selected hospital
      charts of women after delivery were reviewed for receipt of Tdap and demographic
      data. We evaluated postpartum Tdap vaccination rates and conducted multivariate
      analyses to evaluate characteristics that are associated with vaccination. We
      reviewed 1264 charts (658 intervention hospital; 606 comparison hospital) from
      women with completed deliveries. RESULTS: Tdap postpartum vaccination was 0% at
      both hospitals at baseline. In the intervention hospital, the introduction of the
      opt-in order was followed by an increase in postpartum vaccination to 18%. The
      introduction of the standing order approach was followed by a further increase to
      69% (P < .0001). No postpartum Tdap vaccinations were documented in the
      comparison hospital. Postpartum Tdap vaccination in the intervention hospital did
      not differ by demographic characteristics. CONCLUSION: In-hospital ordering
      procedures substantially increased Tdap vaccination coverage in women after
      delivery. Opt-in orders increased coverage that increased substantially with
      standing orders.

PMID- 24096181
TI  - Risk factors for unscheduled delivery in patients with placenta accreta.
AB  - OBJECTIVE: Patients with suspected placenta accreta have improved outcomes with
      scheduled delivery. Our objective was to identify risk factors for unscheduled
      delivery in patients with suspected placenta accreta. STUDY DESIGN: This was a
      cohort study of women with antenatally suspected placenta accreta. Women who
      delivered prior to a planned delivery date were compared with women who had a
      scheduled delivery. Data were analyzed using a Student t test, chi(2), logistic
      regression, and survival analyses. Variables included in the analyses were
      episodes of antenatal vaginal bleeding, preterm premature rupture of membranes
      (PPROM), uterine contractions, prior cesarean deliveries, interpregnancy
      interval, parity, and patient demographic factors. A value of P < .05 was
      considered significant. RESULTS: Seventy-seven women with antenatal suspicion for
      placenta accreta were identified. Thirty-eight (49.4%) had an unscheduled
      delivery. Demographics were similar between groups. Unscheduled patients
      delivered earlier (mean 32.3 vs 35.7 weeks, P < .001) and were significantly more
      likely to have had vaginal bleeding (86.8% vs 35.9%, P < .001) and uterine
      activity (47.4% vs 2.6%, P < .001). Each episode of antenatal vaginal bleeding
      was associated with an increased risk of unscheduled delivery (adjusted odds
      ratio, 3.8; 95% confidence interval, 1.8-7.8). Risk of earlier delivery was even
      greater when associated with PPROM (P < .001). CONCLUSION: Among women with
      suspected placenta accreta, those with antenatal vaginal bleeding were more
      likely to require unscheduled delivery. This risk increases further in the
      setting of PPROM and/or uterine contractions. These clinical factors should be
      considered when determining the optimal delivery gestational age for women with
      placental accreta.

PMID- 24096182
TI  - High risk human papillomavirus at entry to prenatal care and risk of
      preeclampsia.
AB  - OBJECTIVE: To determine the association between high-risk human papillomavirus
      (HR-HPV) and preeclampsia. METHODS: Retrospective cohort study of women with HR
      HPV at entry to prenatal care compared with those with at least 2 normal pap
      smears. Preeclampsia was defined by clinical guidelines. Unadjusted and adjusted
      analyses were performed. RESULTS: Three hundred fourteen women with HR-HPV
      matched with 628 women with normal pap smears. Exposed HR-HPV patients were
      younger, had lower body mass index, systolic and diastolic blood pressure at
      entry to care, and more likely to be nulliparous and smokers. Exposed HR-HPV
      patients were more likely to develop preeclampsia (10.19% vs 4.94%; P = .004;
      adjusted odds ratio, 2.18; 95% confidence interval, 1.31-3.65). Women with HR-HPV
      were also more likely to deliver prematurely at less than 37 and less than 35
      weeks. CONCLUSION: HR-HPV is associated with an almost 2-fold increased risk of
      developing preeclampsia. This warrants a larger study, particularly when HPV
      infection can be prevented with vaccination.

PMID- 24096183
TI  - Plasma cotinine indicates an increased risk of preeclampsia in previous and
      passive smokers.
AB  - OBJECTIVE: Self-reported tobacco smoking in pregnancy has been consistently
      associated with a decreased risk of developing preeclampsia, but the evidence has
      been limited and inconsistent for previous and passive smokers.
      Misclassifications and inaccuracies of self-reported tobacco exposure may
      disguise the true relationship. This study aimed to assess the association of
      gestational hypertension and preeclampsia with maternal smoking status as
      ascertained by plasma cotinine. STUDY DESIGN: This was a prospective study of 605
      pregnant women without chronic hypertension. Maternal smoking status at 24-26
      weeks' gestation was defined by plasma cotinine: >3.0 ng/mL "current smokers,"
      0.20-3.00 ng/mL "previous and passive smokers," and <0.20 ng/mL "nonsmokers."
      RESULTS: Compared to nonsmokers, the risk of developing preeclampsia did not
      change significantly for current smokers, but increased significantly (adjusted
      odds ratio, 6.06; 95% confidence interval, 2.32-15.85; P < .001) for previous and
      passive smokers. There were no significant differences in the risk of developing
      gestational hypertension only. CONCLUSION: Previous and passive smoking may
      increase the risk of preeclampsia. Avoidance of exposure to environmental tobacco
      smoke in pregnancy may decrease the risk of preeclampsia.

PMID- 24096184
TI  - Editor's perspectives--October 2013.

PMID- 24096185
TI  - Possible tool use in a mountain gorilla.
AB  - Here we report a description of putative tool use in wild mountain gorillas. At
      the Dian Fossey Gorilla Fund's Karisoke Research Center in Volcanoes National
      Park (Rwanda), an adult female was observed using a bamboo culm as a ladder for
      her offspring. This is one of only a few documented cases of possible tool use in
      wild gorillas, although tool use behavior is commonly observed in captive
      gorillas. Although the behavior observed may have been incidental, the present
      report in combination with previous evidence (Breuer et al., 2005) suggests that
      tool use in gorillas occurs outside the context of food acquisition and may be
      directed at overcoming physical obstacles in complex rugged microhabitats such as
      bamboo forest and swamps. 

PMID- 24096186
TI  - Electrochemical immunosensor based on ensemble of nanoelectrodes for
      immunoglobulin IgY detection: application to identify hen's egg yolk in tempera
      paintings.
AB  - A nanostructured electrochemical biosensor for detecting proteins of interest in
      work of art, in particular in tempera paintings, is presented. To determine egg
      yolk we focus here on the determination of immunoglobulin IgY. The transducers
      are nanoelectrode ensembles (NEEs), prepared via membrane templated electroless
      deposition of gold. Because of their geometrical and diffusion characteristics,
      NEEs are characterized by significantly low detection limits, moreover they
      display the capability of capturing proteins by interaction with the
      polycarbonate membrane of the NEE. At first, the proteic component of the paint
      is extracted by ultrasonication in an aqueous buffer, then IgY is captured by
      incubation on the NEE. The immunoglobulin is detected by treatment with anti-IgY
      labeled with horse radish peroxidase (Anti-IgY-HRP). The binding of the Anti-IgY
      HRP is detected by recording the electrocatalytic signal caused by addition of
      H2O2 and methylene blue. The sensor detection capabilities are tested by
      analyzing both paint models, prepared in the lab, and real samples, from
      paintings of the XVIII-XX century. Multivariate exploratory analysis is applied
      to classify the voltammetric patterns, confirming the capability to differentiate
      egg-yolk tempera from other kind of tempera binders as well as from acrylic or
      oil paints.

PMID- 24096187
TI  - Neuropsychological, balance, and mobility risk factors for falls in people with
      multiple sclerosis: a prospective cohort study.
AB  - OBJECTIVES: To determine whether impaired performance in a range of vision,
      proprioception, neuropsychological, balance, and mobility tests and pain and
      fatigue are associated with falls in people with multiple sclerosis (PwMS).
      DESIGN: Prospective cohort study with 6-month follow-up. SETTING: A multiple
      sclerosis (MS) physiotherapy clinic. PARTICIPANTS: Community-dwelling people
      (N=210; age range, 21-74y) with MS (Disease Steps 0-5). INTERVENTIONS: Not
      applicable. MAIN OUTCOME MEASURES: Incidence of falls during 6 months' follow-up.
      RESULTS: In the 6-month follow-up period, 83 participants (39.7%) experienced no
      falls, 57 (27.3%) fell once or twice, and 69 (33.0%) fell 3 or more times.
      Frequent falling (>=3) was associated with increased postural sway (eyes open and
      closed), poor leaning balance (as assessed with the coordinated stability task),
      slow choice stepping reaction time, reduced walking speed, reduced executive
      functioning (as assessed with the difference between Trail Making Test Part B and
      Trail Making Test Part A), reduced fine motor control (performance on the 9-Hole
      Peg Test [9-HPT]), and reported leg pain. Increased sway with the eyes closed,
      poor coordinated stability, and reduced performance in the 9-HPT were identified
      as variables that significantly and independently discriminated between frequent
      fallers and nonfrequent fallers (model chi(2)3=30.1, P<.001). The area under the
      receiver operating characteristic curve for this model was .712 (95% confidence
      interval, .638-.785). CONCLUSIONS: The study reveals important balance,
      coordination, and cognitive determinants of falls in PwMS. These should assist
      the development of effective strategies for prevention of falls in this high-risk
      group.

PMID- 24096188
TI  - Adapted physical activity and diet (APAD) during adjuvant breast cancer therapy:
      design and implementation of a prospective randomized controlled trial.
AB  - Exercise practice and appropriate nutrition have been advanced as non
      pharmacological supportive care to reduce side effects related to cancer and its
      treatment, but large sample-sized randomized controlled trials are needed to
      confirm such results. The Adapted Physical Activity and Diet counseling (APAD)
      study is a prospective randomized controlled trial designed to evaluate the
      effectiveness of a 26-week hospital- and home-based lifestyle intervention on
      cancer-related fatigue in women receiving breast cancer adjuvant treatment
      (chemotherapy and radiotherapy). The aim of this paper is to describe the APAD
      study protocol. Study recruitment goal is 264 adult breast cancer women with
      newly, histologically proven, incident and non metastatic breast cancer scheduled
      for 6 cycles of adjuvant chemotherapy followed by radiotherapy. Patients are
      randomized either in the experimental arm with tailored exercise training and
      diet counseling program or in the control arm without any lifestyle intervention
      (usual care). Outcome measures are collected at baseline, and at 15 weeks (i.e.,
      mid-intervention), 26 weeks (i.e., immediately post-intervention), and at 12
      month and 18-month of follow-up. Intervention effect is assessed on fatigue
      (emotional, cognitive, physical), quality-of-life, anxiety, depression, body
      weight and composition. In addition, levels of physical activity, dietary intakes
      and adjuvant therapy observance are measured and a cost-utility analysis will be
      performed. If improvements in fatigue, quality-of-life and a better weight
      control are observed, the APAD study could demonstrate the feasibility and the
      effectiveness of such exercise and nutrition supportive care with limited
      additional cost in patients receiving adjuvant breast cancer therapy.

PMID- 24096189
TI  - Do sleep abnormalities and misaligned sleep/circadian rhythm patterns represent
      early clinical characteristics for developing psychosis in high risk populations?
AB  - Sleep architecture changes, such as slow-wave sleep (SWS) percentage variations
      and reductions in latency and density of rapid eye movement (REM), are found in
      most patients with schizophrenia and are considered to be an important part of
      the pathophysiology of the disorder. In addition to these sleep parameters
      changes, disruptions in sleep homeostasis and the sleep/circadian rhythm also
      occur in these patients. Sleep/circadian rhythm abnormalities negatively affect
      neocortical plasticity and cognition and often precede the diagnosis of the
      illness. Thus, it has been suggested that the sleep/circadian rhythm might be
      involved in the pathophysiology of psychosis. Recent advances in the
      identification of individuals at a high risk for developing schizophrenia allow
      us to investigate several neurobiological processes involved in the development
      of psychosis. In this article, we review the current evidence of the effects of
      sleep parameter abnormalities, disruptions in sleep homeostasis and misalignments
      of sleep circadian rhythm on the early stages of schizophrenia. In addition, we
      discuss the preliminary evidence of sleep and circadian rhythm abnormalities
      during the prodromal stages of psychosis and propose that these abnormalities can
      be explored as potential predictors, as an adjunct to clinical diagnosis, of
      developing a psychotic disorder in at risk populations. 

PMID- 24096192
TI  - A new stress model, a scream sound, alters learning and monoamine levels in rat
      brain.
AB  - Most existing animal models for stress involve the simultaneous application of
      physical and psychological stress factors. In the current study, we described and
      used a novel psychological stress model (scream sound stress). To study the
      validity of it, we carried out acute and chronic scream sound stress. First,
      adult Sprague-Dawley (SD) rats were randomly divided into white noise, stress and
      background groups. The white noise group and stress group were treated with white
      noise and scream sound for 4h in the morning respectively. Compared with white
      noise and background groups, exposure to acute scream sound increased
      corticosterone (CORT) level and decreased latency in Morris water maze (MWM)
      test. The levels of noradrenaline (NE), dopamine (DA), 5-hydroxytryptamine (5
      HT), 3,4-dihydroxyphenylacetic acid (DOPAC), homovanillic acid (HVA) and 5
      hydroxyindoleacetic acid (5-HIAA) were altered in the striatum, hypothalamus and
      hippocampus of stress rats. Second, adult SD rats were randomly divided into
      background and stress groups, which were treated with scream sound for three
      weeks. Exposure to chronic scream sound suppressed body weight gain, increased
      corticosterone (CORT) level, influenced the morphology of adrenal gland, improved
      spleen and thymus indices, and decreased latency in MWM test. NE, DA, DOPAC, HVA
      and 5-HIAA levels were also altered in the brain of stress rats. Our results
      suggested that scream sound, as a novel stressor, facilitated learning ability,
      as well as altered monoamine levels in the rat brain. Moreover, scream sound is
      easy to apply and can be applied in more animals at the same time. 

PMID- 24096191
TI  - Female rats exposed to stress and alcohol show impaired memory and increased
      depressive-like behaviors.
AB  - Exposure to daily life stressors is associated with increases in anxiety,
      depression, and overall negative affect. Alcohol or other psychoactive drugs are
      often used to alleviate stress effects. While females are more than twice as
      likely to develop mood disorders and are more susceptible to dependency than
      males, they are infrequently examined. In this study, female rats received no
      stress/no alcohol control (CON), alcohol alone (ALC), stress alone (STR), or
      stress plus alcohol (STR+ALC). Stress consisted of restraint for 6h/day/7days,
      and alcohol was administered immediately following restraint via gastric gavage
      at a dose of 2.0g/kg. Dependent measures included tests utilizing object
      recognition (OR), Y-maze, elevated plus maze (EPM), forced swim (FST), blood
      alcohol content, corticosterone levels, and body weights. ALC, STR+ALC, but not
      stress alone, impaired memory on OR. All treatments impaired spatial memory on
      the Y-maze. Anxiety was not affected on the EPM, but rats treated with alcohol or
      in combination with stress showed increased immobility on the FST, suggestive of
      alcohol-induced depression. Previously, we found alcohol reversed deleterious
      effects of stress on memory and mood in males, but current results show that
      females reacted negatively when the two treatments were combined. Thus, responses
      to alcohol, stress and their combination suggest that sex specific treatments are
      needed for stress-induced behavioral changes and that self-medicating with
      alcohol to cope with stress maybe deleterious in females. 

PMID- 24096193
TI  - The growth of glioblastoma orthotopic xenografts in nude mice is directly
      correlated with impaired object recognition memory.
AB  - Cognitive dysfunction is found in patients with brain tumors and there is a need
      to determine whether it can be replicated in an experimental model. In the
      present study, the object recognition (OR) paradigm was used to investigate
      cognitive performance in nude mice, which represent one of the most important
      animal models available to study human tumors in vivo. Mice with orthotopic
      xenografts of the human U87MG glioblastoma cell line were trained at 9, 14, and
      18days (D9, D14, and D18, respectively) after implantation of 5*10(5) cells. At
      D9, the mice showed normal behavior when tested 90min or 24h after training and
      compared to control nude mice. Animals at D14 were still able to discriminate
      between familiar and novel objects, but exhibited a lower performance than
      animals at D9. Total impairment in the OR memory was observed when animals were
      evaluated on D18. These alterations were detected earlier than any other clinical
      symptoms, which were observed only 22-24days after tumor implantation. There was
      a significant correlation between the discrimination index (d2) and time after
      tumor implantation as well as between d2 and tumor volume. These data indicate
      that the OR task is a robust test to identify early behavior alterations caused
      by glioblastoma in nude mice. In addition, these results suggest that OR task can
      be a reliable tool to test the efficacy of new therapies against these tumors. 

PMID- 24096194
TI  - Osteochondromas around the ankle: Report of a case and literature review.
AB  - INTRODUCTION: An osteochondroma or exostosis is a benign bone tumour consisting
      of a bony outgrowth covered by a cartilage cap that occurs commonly in the
      metaphysis of long bones, mainly the distal femur, proximal tibia and proximal
      humerus. PRESENTATION OF CASE: We describe an unusual case of a distal tibia
      osteochondroma affecting the lateral malleolus of a young girl. DISCUSSION: Most
      osteochondromas are asymptomatic and seen incidentally during radiographic
      examination. Osteochondromas are rarely localized in the foot and ankle.
      CONCLUSION: Although most of the osteochondromas in children should be treated
      conservatively until skeletal maturity, those affecting the distal tibia or
      fibula should be treated with surgical excision in order to prevent ankle
      deformity, syndesmotic lesions or even fracture due to the expanding nature of
      this benign tumour.

PMID- 24096190
TI  - Age, plasticity, and homeostasis in childhood brain disorders.
AB  - It has been widely accepted that the younger the age and/or immaturity of the
      organism, the greater the brain plasticity, the young age plasticity privilege.
      This paper examines the relation of a young age to plasticity, reviewing human
      pediatric brain disorders, as well as selected animal models, human developmental
      and adult brain disorder studies. As well, we review developmental and childhood
      acquired disorders that involve a failure of regulatory homeostasis. Our core
      arguments are as follows: 

PMID- 24096195
TI  - Evaluation of quantitative performance of sequential immobilized metal affinity
      chromatographic enrichment for phosphopeptides.
AB  - We evaluated a sequential elution protocol from immobilized metal affinity
      chromatography (SIMAC) employing gallium-based immobilized metal affinity
      chromatography (IMAC) in conjunction with titanium dioxide-based metal oxide
      affinity chromatography (MOAC). The quantitative performance of this SIMAC
      enrichment approach, assessed in terms of repeatability, dynamic range, and
      linearity, was evaluated using a mixture composed of tryptic peptides from
      caseins, bovine serum albumin, and phosphopeptide standards. Although our data
      demonstrate the overall consistent performance of the SIMAC approach under
      various loading conditions, the results also revealed that the method had limited
      repeatability and linearity for most phosphopeptides tested, and different
      phosphopeptides were found to have different linear ranges. These data suggest
      that, unless additional strategies are used, SIMAC should be regarded as a
      semiquantitative method when used in large-scale phosphoproteomics studies in
      complex backgrounds. 

PMID- 24096197
TI  - Oligonucleotides labeled with single fluorophores as sensors for deoxynucleotide
      triphosphate binding by DNA polymerases.
AB  - Oligonucleotides labeled with a single fluorophore (fluorescein or
      tetramethylrhodamine) have been used previously as fluorogenic substrates for a
      number of DNA modifying enzymes. Here, it is shown that such molecules can be
      used as fluorogenic probes to detect the template-dependent binding of
      deoxynucleotide triphosphates by DNA polymerases. Two polymerases were used in
      this work: the Klenow fragment of the Escherichia coli DNA polymerase I and the
      Bacillus stearothermophilus polymerase, Bst. When complexes of these polymerases
      with dye-labeled hairpin-type oligonucleotides were mixed with various
      deoxynucleotide triphosphates in the presence of Sr2+ as the divalent metal
      cation, the formation of ternary DNA-polymerase-dNTP complexes was detected by
      concentration-dependent changes in the fluorescence intensities of the dyes.
      Fluorescein- and tetramethylrhodamine-labeled probes of identical sequences
      responded differently to the two polymerases. With Bst polymerase, the
      fluorescence intensities of all probes increased with the next correct dNTP; with
      Klenow polymerase, tetramethylrhodamine-labeled probes increased their
      fluorescence, but the intensity of fluorescein-labeled probes decreased on
      formation of ternary complexes with the correct incoming nucleotides. The use of
      Sr2+ as the divalent metal ion allowed the formation of catalytically inactive
      ternary complexes and obviated the need for using 2',3'-dideoxy-terminated
      oligonucleotides as would have been needed in the case of Mg2+ as the metal ion.

PMID- 24096196
TI  - Cleavage of pro-tumor necrosis factor alpha by ADAM metallopeptidase domain 17: a
      fluorescence-based protease assay cleaves its natural protein substrate.
AB  - A fluorescence-based Adam 17 activity assay that cleaves pro-tumor necrosis
      factor alpha (pro-TNFalpha) protein substrate has been developed. The key to the
      assay was site-specific labeling of a fluorescence dye to the N-terminal end of
      the substrate protein, which was achieved by the protein ligation method. The
      protease cleavage reaction was monitored by fluorescence polarization. This
      homogeneous assay allows reaction progress to be recorded kinetically in real
      time. The results were validated by gel electrophoresis and high-performance
      liquid chromatography. As expected, the reaction could be inhibited by an ADAM
      metallopeptidase domain 17 (Adam 17) active site inhibitor. Interestingly, the
      reaction rate of pro-TNFalpha cleavage by Adam 17 was also reduced by a small
      molecule binding to pro-TNFalpha protein, the substrate of the reaction. This
      small molecule, however, did not affect the activity of Adam 17 to its peptide
      substrate. These results demonstrate that this natural protein substrate-based
      fluorescent assay was able to identify the inhibitor binding to substrate protein
      in addition to that binding to the protease itself. Comparing this protein
      substrate with a short peptide substrate, the activity of Adam 17 showed
      different pH profiles. With pro-TNFalpha the optimal pH was approximately 7.4,
      whereas with the peptide substrate the optimal pH was higher than 9.0. 

PMID- 24096198
TI  - Health-related quality of life improves during the first six months after cardiac
      arrest and hypothermia treatment.
AB  - AIM OF THE STUDY: To investigate whether there were any changes in and
      correlations between anxiety, depression and health-related quality of life
      (HRQoL) over time, between hospital discharge and one and six months after
      cardiac arrest (CA), in patients treated with therapeutic hypothermia (TH).
      METHOD: During a 4-year period at three hospitals in Sweden, 26 patients were
      prospectively included after CA treated with TH. All patients completed the
      questionnaires Hospital Anxiety and Depression Scale (HADS), Euroqol (EQ5D),
      Euroqol visual analogue scale (EQ-VAS) and Short Form 12 (SF12) at three
      occasions, at hospital discharge, and at one and 6 months after CA. RESULT: There
      was improvement over time in HRQoL, the EQ5D index (p=0.002) and the SF12
      physical component score (PCS) (p=0.005). Changes over time in anxiety and
      depression were not found. Seventy-three percent of patients had an EQ-VAS score
      below 70 (scale 0-100) on overall health status at discharge from hospital; at 6
      months the corresponding figure was 41%. Physical problems were the most common
      complaint affecting HRQoL. A correlation was found between depression and HRQoL,
      and this was strongest at six months (rs=-0.44 to -0.71, p<=0.001). CONCLUSION:
      HRQoL improves over the first 6 months after a CA. Patients reported lower levels
      of HRQoL on the physical as compared to mental component. The results indicate
      that the less anxiety and depression patients perceive, the better HRQoL they
      have and that time can be an important factor in recovery after CA.

PMID- 24096199
TI  - Removal of arsenic from groundwater by using a native isolated arsenite-oxidizing
      bacterium.
AB  - Arsenic (As) contamination of groundwater is a significant public health concern.
      In this study, the removal of arsenic from groundwater using biological processes
      was investigated. The efficiency of arsenite (As(III)) bacterial oxidation and
      subsequent arsenate (As(V)) removal from contaminated groundwater using bacterial
      biomass was examined. A novel As(III)-oxidizing bacterium (As7325) was isolated
      from the aquifer in the blackfoot disease (BFD) endemic area in Taiwan. As7325
      oxidized 2300MUg/l As(III) using in situ As(III)-contaminated groundwater under
      aerobic conditions within 1d. After the oxidation of As(III) to As(V), As(V)
      removal was further examined using As7325 cell pellets. The results showed that
      As(V) could be adsorbed efficiently by lyophilized As7325 cell pellets, the
      efficiency of which was related to lyophilized cell pellet concentration. Our
      study conducted the examination of an alternative technology for the removal of
      As(III) and As(V) from groundwater, indicating that the oxidation of As(III)
      contaminated groundwater by native isolated bacterium, followed by As(V) removal
      using bacterial biomass is a potentially effective technology for the treatment
      of As(III)-contaminated groundwater. 

PMID- 24096200
TI  - Formulation design for target delivery of iron nanoparticles to TCE zones.
AB  - Nanoparticles of zero-valent iron (NZVI) are effective reducing agents for some
      dense non-aqueous phase liquid (DNAPL) contaminants such as trichloroethylene
      (TCE). However, target delivery of iron nanoparticles to DNAPL zones in the
      aquifer remains an elusive feature for NZVI technologies. This work discusses
      three strategies to deliver iron nanoparticles to DNAPL zones. To this end, iron
      oxide nanoparticles coated with oleate (OL) ions were used as stable analogs for
      NZVI. The OL-coated iron oxide nanoparticles are rendered lipophilic via (a) the
      addition of CaCl2, (b) acidification, or (c) the addition of a cationic
      surfactant, benzethonium chloride (BC). Mixtures of OL and BC show promise as a
      target delivery strategy due to the high stability of the nanoparticles in water,
      and their preferential partition into TCE in batch experiments. Column tests show
      that while the OL-BC coated iron oxide nanoparticles remain largely mobile in TCE
      free columns, a large fraction of these particles are retained in TCE
      contaminated columns, confirming the effectiveness of this target delivery
      strategy. 

PMID- 24096201
TI  - The origin of magnetism in transition metal-doped ZrO2 thin films: experiment and
      theory.
AB  - We have investigated the magnetic properties of Fe/Co/Ni-doped ZrO2 laser ablated
      thin films in comparison with the known results of Mn-doped ZrO2, which is
      thought to be a promising material for spintronics applications. It is found that
      doping with a transition metal can induce room temperature ferromagnetism in
      'fake' diamond. Theoretical analysis based on density functional theory confirms
      the experimental measurements, by revealing that the magnetic moments of Mn- and
      Ni-doped ZrO2 thin films are much larger than that of Fe- or Co-doped ZrO2 thin
      films. Most importantly, our calculations confirm that Mn- and Ni-doped ZrO2 show
      a ferromagnetic ground state in comparison to Co- and Fe-doped ZrO2, which favor
      an antiferromagnetic ground state.

PMID- 24096203
TI  - Local knowledge, use pattern and geographical distribution of Moringa oleifera
      Lam. (Moringaceae) in Nigeria.
AB  - ETHNO-PHARMACOLOGICAL RELEVANCE: All parts of Moringa oleifera are medicinally
      valuable with overlapping uses in treating myriads of ailments and diseases
      including body pains and weakness, fever, asthma, cough, blood pressure,
      arthritis, diabetes, epilepsy, wound, and skin infection. Moringa also has robust
      ability to challenge terminal diseases such as HIV/AIDs infections, chronic
      anemia, cancer, malaria and hemorrhage. The present study was to obtain
      ethnobotanical information on the use and local knowledge variation, geographical
      distribution, and to collect different landraces of Moringa oleifera from the
      different agro-ecological regions in Nigeria, for further studies. MATERIALS AND
      METHODS: Ethnobotanical data were collected through face to face interviews, semi
      structured questionnaires and discussions with selected people who had knowledge
      about the plant. The fidelity level (FL %) and use value for different use
      categories of Moringa oleifera and its parts were estimated. The variation in
      ethnobotanical knowledge was evaluated by comparing the mean use value among
      ethnic, gender and age groups using sample T test. Garmi GPS was used to
      determine the locations (latitude and longitude) and height in different areas to
      assess the geographical spread of the species. RESULTS: Seven (7) categories of
      use (Food, medicine, fodder, fencing, firewood, gum and coagulant) were recorded
      for Moringa oleifera. Food and medicinal uses showed highest fidelity level while
      the leaves and the seeds were the plant parts most utilized for the same
      purposes. There were significant differences among the ethnic, gender and age
      groups regarding the ethno-botanical use value. The geographical distribution
      pattern shows that the Moringa oleifera is well distributed in all ecological
      zones of Nigeria, well adapted to the varied climatic conditions and gaining
      unprecedented awareness among the people. CONCLUSION: Though considered an
      introduced species, Moringa oleifera has found wide acceptance, recognition and
      usefulness among the various ethnicities in the studied areas. The sources of
      introduction, domestication and ethnic differentiation influenced the
      distribution pattern across the geographical areas.

PMID- 24096202
TI  - Shenyuan, an extract of American Ginseng and Corydalis Tuber formula, attenuates
      cardiomyocyte apoptosis via inhibition of endoplasmic reticulum stress and
      oxidative stress in a porcine model of acute myocardial infarction.
AB  - ETHNOPHARMACOLOGICAL RELEVANCE: The decoction of American Ginseng and Corydalis
      Tuber has been widely used for treatment of cardiovascular diseases due to their
      anti-ischemic and anti-arrhythmic effects. The aim of this study is to evaluate
      the anti-apoptotic effect of Shenyuan, which is composed of the bioactive
      components extracted from the mixture of American Ginseng and Corydalis Tuber,
      and to explore potential mechanisms involved in the regulation of apoptosis.
      MATERIALS AND METHODS: A porcine model of acute myocardial infarction (AMI) was
      established by ligation of the left anterior descending coronary artery. Thirty
      eight pigs were randomized into six groups: Group S, sham (n=6); Group C, AMI
      controls (n=8); Group L, AMI+low-dose Shenyuan (240 mg/kg.d, n=6); Group M,
      AMI+moderate-dose Shenyuan (320 mg/kg.d, n=6); Group H, AMI+high-dose Shenyuan
      (400 mg/kg.d, n=6); Group B, AMI+Metoprolol Tartrate (1 mg/kg.d, n=6). The
      treatment of Shenyuan or Metoprolol started one week before AMI and continued for
      another two weeks after AMI. RESULTS: Treatment with all doses of Shenyuan as
      well as Metoprolol produced a significant decrease of apoptotic index (P < 0.05),
      which was confirmed by TUNEL staining method. This anti-apoptotic effect was
      accompanied by less release of cardiac enzymes and limit of infarct size. In
      Group H, levels of MDA, 8-iso-prostaglandin F2alpha, GRP78/bip, calregulin,
      CHOP/GADD153, Bax, caspase-3, cleaved caspase-3 and activity of caspase-3 were
      reduced, while GSH, SOD, Bcl-2 and the Bcl-2/Bax ratio were significantly
      increased (P < 0.05). In groups M and L, some results did not show statistical
      difference. There was no statistical difference in cardiac function between
      treatment groups and Group C. CONCLUSION: Shenyuan treatment significantly
      inhibited ERS and oxidative stress, balanced the Bcl-2/Bax ratio, suppressed
      activation of caspase-3, and finally exerted an anti-apoptotic effect in pigs
      with a large anterior wall AMI. This was accompanied by less release of cardiac
      enzymes and limit of infarct size. Shenyuan treatment inhibited apoptosis and may
      have a therapeutic role in improving the natural process of AMI.

PMID- 24096204
TI  - Associations and propositions: the case for a dual-process account of learning in
      humans.
AB  - We review evidence that supports the conclusion that people can and do learn in
      two distinct ways - one associative, the other propositional. No one disputes
      that we solve problems by testing hypotheses and inducing underlying rules, so
      the issue amounts to deciding whether there is evidence that we (and other
      animals) also rely on a simpler, associative system, that detects the frequency
      of occurrence of different events in our environment and the contingencies
      between them. There is neuroscientific evidence that associative learning occurs
      in at least some animals (e.g., Aplysia californica), so it must be the case that
      associative learning has evolved. Since both associative and propositional
      theories can in principle account for many instances of successful learning, the
      problem is then to show that there are at least some cases where the two classes
      of theory predict different outcomes. We offer a demonstration of cue competition
      effects in humans under incidental conditions as evidence against the argument
      that all such effects are based on cognitive inference. The latter supposition
      would imply that if the necessary information is unavailable to inference then no
      cue competition should occur. We then discuss the case of unblocking by
      reinforcer omission, where associative theory predicts an irrational solution to
      the problem, and consider the phenomenon of the Perruchet effect, in which
      conscious expectancy and conditioned response dissociate. Further discussion
      makes use of evidence that people will sometimes provide one solution to a
      problem when it is presented to them in summary form, and another when they are
      presented in rapid succession with trial-by trial information. We also
      demonstrate that people trained on a discrimination may show a peak shift
      (predicted by associative theory), but given the time and opportunity to detect
      the relationships between S+ and S-, show rule-based behavior instead. Finally,
      we conclude by presenting evidence that research on individual differences
      suggests that variation in intelligence and explicit problem solving ability are
      quite unrelated to variation in implicit (associative) learning, and briefly
      consider the computational implications of our argument, by asking how both
      associative and propositional processes can be accommodated within a single
      framework for cognition. 

PMID- 24096205
TI  - Development of a liquid chromatography-tandem mass spectrometry with ultrasound
      assisted extraction method for the simultaneous determination of sudan dyes and
      their metabolites in the edible tissues and eggs of food-producing animals.
AB  - A liquid chromatography-tandem mass spectrometry (LC-MS/MS) was developed for the
      simultaneous determination of sudan I, sudan II, sudan III, sudan IV, and their
      metabolites such as 4-aminoazobenzene and ortho-aminoazotoluole in 12 animal
      derived foods (including the muscle and liver of swine, muscle, liver and skin of
      chicken and duck, muscle and skin of fish, as well as the eggs of hen and duck).
      Sample preparation procedure included ultrasound-assisted extraction with
      acetonitrile, defatting with n-hexane and final clean-up with solid phase
      extraction (SPE) on Aluminum B cartridges. The detection and quantification of
      the 6 sudan dyes and their metabolites were performed by a reversed-phase liquid
      chromatography coupled with electrospray ionization triple quadrupole mass
      spectrometry (LC/ESI-MS/MS). The CCalphas and the CCbetas of various samples
      varied from 0.03MUg/kg to 0.12MUg/kg, 0.09MUg/kg to 0.19MUg/kg, respectively. The
      recoveries of spiked sample from 0.2MUg/kg to 0.8MUg/kg ranged from 61.9% to
      87.4% with the relative standard deviations of less than 19.1%. Performances of
      the whole analytical procedure meet the criteria established by the European
      Commission for mass spectrometric detection. 

PMID- 24096206
TI  - Metabolite profiling and identification of triptolide in rats.
AB  - The purpose of the current study was to investigate the metabolite profile of
      [(3)H]triptolide in rats. The separation and characterisation techniques used to
      identify the major metabolites were high-performance liquid chromatography-online
      radiodetector, ultra-performance liquid chromatography-quadrupole time-of-flight
      mass spectrometry, and nuclear magnetic resonance. In all, 33 major metabolites
      were detected. The major components found in the rat plasma included the parent
      drug and its monohydroxy- and dihydroxy-metabolites. Reference standards for the
      monohydroxy-metabolites were obtained either by the incubation of the parent drug
      with rat liver microsomes or by microbial transformation with Cunninghamella
      blakesleana. The metabolites' structures were identified as 17-hydroxytriptolide,
      16-hydroxytriptolide, tripdiolide, and 15-hydroxytriptolide. The major
      metabolites found in male rat urine included the monohydroxy-, dihydroxy-, and
      trihydroxy-metabolites. The major metabolites in female rat urine were the
      monohydroxy- and dihydroxy-metabolites, as well as sulphates of the monohydroxy
      metabolites. A glutathione adduct, multiple hydroxy-metabolites, and a number of
      unidentified metabolites were detected in the bile and faeces of male rats.
      Sulphates of monohydroxy-metabolites were detected in the bile and faeces of
      female rats. 

PMID- 24096207
TI  - Transcription regulation and chromatin structure in the pluripotent ground state.
AB  - The use of mouse embryonic stem cells (ESCs) has provided invaluable insights
      into transcription and epigenetic regulation of pluripotency and self-renewal.
      Many of these insights were gained in mouse ESCs that are derived and maintained
      using serum, either on feeder cells or supplemented with the cytokine leukemia
      inhibitory factor (LIF). These 'serum' ESCs are in a metastable state
      characterized by the expression of many lineage-specifying genes. The use of two
      small-molecule kinase inhibitors (2i), targeting mitogen-activated protein kinase
      (MEK) and glycogen synthase kinase-3 (GSK3), has enabled derivation of mouse ESCs
      in defined serum-free conditions. These '2i' ESCs are more homogeneous in
      morphology and gene expression than serum ESCs, and are postulated to represent
      the ground state of pluripotency. Recent studies have shown that the epigenome
      and transcriptome of 2i and serum ESCs are markedly different, suggesting that
      these ESCs represent two distinct states of pluripotency regulated by different
      factors and pathways. There is growing evidence that the 2i ESCs closely parallel
      the early blastocyst cells of the inner cell mass (ICM) or even earlier stages,
      while serum cells possibly reflect later stages. In this review, we will focus on
      the difference in chromatin structure, transcription regulation and cell cycle
      regulation between ground state pluripotent 2i ESCs and serum ESCs, and compare
      to corresponding data in embryos if available. This article is part of a Special
      Issue entitled: Chromatin and epigenetic regulation of animal development. 

PMID- 24096208
TI  - The nature of mind wandering during reading varies with the cognitive control
      demands of the reading strategy.
AB  - Prior studies of mind wandering find the default network active during mind
      wandering, but these studies have yielded mixed results concerning the role of
      cognitive control brain regions during mind wandering. Mind wandering often
      interferes with reading comprehension, and prior neuroimaging studies of
      discourse comprehension and strategic reading comprehension have shown that there
      are at least two networks of brain regions that support strategic discourse
      comprehension: a domain-general control network and a network of regions
      supporting coherence-building comprehension processes. The present study was
      designed to further examine the neural correlates of mind wandering by examining
      mind wandering during strategic reading comprehension. Participants provided
      ratings of mind wandering frequency that were used to investigate interactions
      between the strategy being performed and brain regions whose activation was
      modulated by wind wandering. The results support prior findings showing that
      cognitive control regions are at times more active during mind wandering than
      during a task with low control demands, such as rereading. This result provides
      an initial examination of the neural correlates of mind wandering during
      discourse comprehension and shows that the processes being engaged by the primary
      task need to be considered when studying mind wandering. The results also
      replicate, in a different learning domain, prior findings of key brain areas
      associated with different reading strategies. 

PMID- 24096209
TI  - Ethanol- and acetaldehyde-induced cholinergic imbalance in the hippocampus of
      Aldh2-knockout mice does not affect nerve growth factor or brain-derived
      neurotrophic factor.
AB  - Neurotrophins, including nerve growth factor (NGF) and brain-derived neurotrophic
      factor (BDNF), play an important role in the maintenance of cholinergic-neuron
      function. The objective of this study was to investigate whether ethanol (EtOH)-
      and acetaldehyde (AcH)- induced cholinergic effects would cause neurotrophic
      alterations in the hippocampus of mice. We used Aldh2 knockout (Aldh2-KO) mice, a
      model of aldehyde dehydrogenase 2 (ALDH2)-deficiency in humans, to examine the
      effects of acute administration of EtOH and the role of AcH. Hippocampal slices
      were collected and the mRNA and protein levels of choline acetyltransferase
      (ChAT), acetylcholinesterase (AChE), NGF and BDNF were analyzed 30 min after the
      i.p. administration of EtOH (0.5, 1.0, or 2.0 g/kg). We show that treatment with
      2.0 g/kg of EtOH decreased ChAT mRNA and protein levels in Aldh2-KO mice but not
      in wild-type (WT) mice, which suggests a role for AcH in the mechanism of action
      of EtOH. The administration of 2.0 g/kg of EtOH increased AChE mRNA in both
      strains of mice. EtOH failed to change the levels of NGF or BDNF at any dose.
      Aldh2-KO mice exhibited a distinctly lower expression of ChAT and a higher
      expression of NGF both at mRNA and protein levels in the hippocampus compared
      with WT mice. Our observations suggest that administration of EtOH and elevated
      AcH can alter cholinergic markers in the hippocampus of mice, and this effect did
      not change the levels of NGF or BDNF.

PMID- 24096210
TI  - A low-density culture method of cerebellar granule neurons with paracrine support
      applicable for the study of neuronal morphogenesis.
AB  - Cerebellar granule neuronal cultures have been used to study the molecular
      mechanisms underlying neuronal functions, including neuronal morphogenesis.
      However, a limitation of this system is the difficulty to analyze isolated
      neurons because these are required to be maintained at a high density. Therefore,
      in the present study, we aimed to develop a simple and cost-effective method for
      culturing low-density cerebellar granule neurons. Cerebellar granule cells at two
      different densities (low- and high-density) were co-cultivated in order for the
      low-density culture to be supported by the paracrine signals from the high
      density culture. This method enabled morphology analysis of isolated cerebellar
      granule neurons without astrocytic feeder cultures or supplements such as B27.
      Using this method, we investigated the function of a polarity factor. Studies
      using hippocampal neurons suggested that glycogen synthase kinase-3 (GSK-3) is an
      essential regulator of neuronal polarity, and inhibition of GSK-3 results in the
      formation of multiple axons. Pharmacological inhibitors for GSK-3 (6
      bromoindirubin-3'-oxime and lithium chloride) did not cause the formation of
      multiple axons of cerebellar granule neurons but significantly reduced their
      length. Consistent results were obtained by introducing kinase-dead form of GSK-3
      beta (K85A). These results indicated that GSK-3 is not directly involved in the
      control of neuronal polarity in cerebellar granule neurons. Overall, this study
      provides a simple method for culturing low-density cerebellar granule neurons and
      insights in to the neuronal-type dependent function of GSK-3 in neuronal
      morphogenesis. 

PMID- 24096211
TI  - Sodium hydrosulfide prevents hypoxia-induced behavioral impairment in neonatal
      mice.
AB  - Hypoxic encephalopathy is a common cause of neonatal seizures and long-term
      neurological abnormalities. Endogenous hydrogen sulfide (H2S) may have multiple
      functions in brain. The aim of this study is to investigate whether sodium
      hydrosulfide (NaHS), a H2S donor, provides protection against neonatal hypoxia
      induced neurobehavioral deficits. Neonatal mice were subjected to hypoxia (5%
      oxygen for 120min) at postnatal day 1 and received NaHS (5.6mg/kg) once daily for
      3d. Neurobehavioral toxicity was examined at 3-30d after hypoxia. Treatment with
      NaHS significantly attenuated the delayed development of sensory and motor
      reflexes induced by hypoxia up to two weeks after the insult. Moreover, NaHS
      improved the learning and memory performance of hypoxic animals as indicated in
      Morris water maze test at 30d after hypoxia. In mice exposed to hypoxia,
      treatment with NaHS enhanced expression of brain derived neurotrophic factor
      (BDNF) in the hippocampus. Furthermore, the protective effects of NaHS were
      associated with its ability to repress the hypoxia-induced nitric oxide synthase
      (NOS) activity and nitric oxide production in the hippocampus of mice brain.
      Taken together, these results suggest that the long-lasting beneficial effects of
      NaHS on hypoxia-induced neurobehavioral deficits are mediated, at least in part,
      by inducing BDNF expression and suppressing NOS activity in the brain of mice. 

PMID- 24096212
TI  - Morphine could increase apoptotic factors in the nucleus accumbens and prefrontal
      cortex of rat brain's reward circuitry.
AB  - The nucleus accumbens (NAc) and prefrontal cortex (PFC) are two parts of neuronal
      reward circuit involved in motivated and goal-directed behaviors. Some data
      suggest that morphine is toxic to neurons and induces apoptosis, while other
      evidence shows that morphine could have beneficial effects against cell death.
      This study was designed to evaluate the effect of morphine on apoptosis by
      measuring the expression of apoptotic proteins in two important regions, the NAc
      and PFC, in the rat brain's reward circuitry. Morphine subchronic administration
      in different doses (0.5, 5 and 10mg/kg) in conditioned place preference (CPP)
      paradigm (3 times in 3 days, for each dose in each group of rats) was used to
      induce its rewarding effect. Then, the expression of four apoptotic factors; Bax,
      Bcl2, caspase3 and PARP, in the NAc and PFC were assessed using the Western blot
      technique. All of morphine-treated groups showed increase of apoptotic factors in
      these regions. In the NAc, morphine significantly increased the Bax/Bcl-2 ratio,
      caspase3 and PARP in the lowest dose (0.5mg/kg) but in the PFC considerable
      increase was seen in dose of 5mg/kg. Elevation of apoptotic factors in the NAc
      and PFC implies that morphine can affect the molecular mechanisms which interfere
      with apoptosis through different receptors. Our findings suggest that the NAc and
      PFC may have a different distribution of receptors which become active in
      different doses of morphine. 

PMID- 24096213
TI  - MicroRNAs dysregulation in epilepsy.
AB  - Epilepsy is a syndrome characterized by recurrent spontaneous seizures due to
      neuronal hyperactivity in the brain. MicroRNAs (miRNAs) are small, non-coding
      RNAs that regulate post-transcriptional expression of protein-coding mRNAs, which
      may have key roles in the pathogenesis of neurological disorders. Evidence
      indicates that miRNAs are emerging as a critical new layer of gene expression
      regulation with implications for the cause and treatment of epilepsy.
      Accumulating studies in epilepsy suggest that numerous specific miRNAs are
      dysregulated. Recent studies have explored several target genes and pathways of
      miRNAs in order to find out therapeutic approaches to epilepsy. Here, we review
      current findings regarding miRNA research in humans and animal models to provide
      a solid foundation for further research aiming at understanding the potential
      contribution of miRNAs to epilepsy pathophysiology.

PMID- 24096215
TI  - Aesthetic practice in Nepal.

PMID- 24096216
TI  - Clinical and electroencephalographic profile of children.
AB  - BACKGROUND: Reports on pediatric electroencephalogram of Nepalese patients are
      rare. OBJECTIVE: We aimed to study the relationship between provisional clinical
      and electrophysiological diagnoses of pediatric patients with documentation of
      demographic profiles, and type and frequency of the disorders/diseases. METHODS:
      Electroencephalographic reports of 634 children from 2006 to 2009 were analyzed
      at neurophysiology laboratory, department of Basic and Clinical Physiology, B. P.
      Koirala Institute of Health Sciences, Dharan, Nepal, retrospectively. Chi-Square
      test was applied after detail descriptive statistics. RESULTS: Male and female
      were 72.2 % (n=458/634) and 27.76 % (n=176/634) respectively. Most frequent EEG
      abnormality was seizure disorder (n=370, 59.39%), then febrile seizure (n= 94,
      15.08%) and birth asphyxia with hypoxic-induced encephalopathy (n=68, 10.91%).
      Electroencephalogram showed significant epileptiform discharges in seizure
      disorder (p=0.001, OR= 2.26, 95 % CI= 1.61 to 3.18) and in cerebral palsy
      (p=0.049, OR=6.88, 95 % CI=0.89 to 145.95), specifically in 6 to 12 (p=0.001,
      OR=2.94, 95 % CI=1.43 to 6.06) and one to five (p=0.019) years, respectively.
      Electroencephalogram detected significantly less epileptiform discharges
      (p=0.001, OR=0.25, 95 % CI= 0.15 to 0.42) in febrile seizure specifically in 1 to
      5 years (p=0.003, OR=0.16, 95 % CI= 0.04 to 0.63). CONCLUSION: Predominant
      Electroencephalographic abnormality was seizure disorder, followed by febrile
      seizure and birth asphyxia with hypoxic-induced encephalopathy respectively.
      Electroencephalographic abnormality was highly associated with seizure disorder
      and cerebral palsy but was not associated with febrile seizure.

PMID- 24096214
TI  - Depression, anxiety-like behavior and memory impairment are associated with
      increased oxidative stress and inflammation in a rat model of social stress.
AB  - In the present study, we have examined the behavioral and biochemical effect of
      induction of psychological stress using a modified version of the resident
      intruder model for social stress (social defeat). At the end of the social defeat
      protocol, body weights, food and water intake were recorded, depression and
      anxiety-like behaviors as well as memory function was examined. Biochemical
      analysis including oxidative stress measurement, inflammatory markers and other
      molecular parameters, critical to behavioral effects were examined. We observed a
      significant decrease in the body weight in the socially defeated rats as compared
      to the controls. Furthermore, social defeat increased anxiety-like behavior and
      caused memory impairment in rats (P<0.05). Socially defeated rats made
      significantly more errors in long term memory tests (P<0.05) as compared to
      control rats. Furthermore, brain extracellular signal-regulated kinase-1/2
      (ERK1/2), and an inflammatory marker, interleukin (IL)-6 were activated (P<0.05),
      while the protein levels of glyoxalase (GLO)-1, glutathione reductase (GSR)-1,
      calcium/calmodulin-dependent protein kinase type (CAMK)-IV, cAMP-response-element
      binding protein (CREB) and brain-derived neurotrophic factor (BDNF) were
      significantly less (P<0.05) in the hippocampus, but not in the prefrontal cortex
      and amygdala of socially defeated rats, when compared to control rats. We suggest
      that social defeat stress alters ERK1/2, IL-6, GLO1, GSR1, CAMKIV, CREB, and BDNF
      levels in specific brain areas, leading to oxidative stress-induced anxiety
      depression-like behaviors and as well as memory impairment in rats. 

PMID- 24096217
TI  - Fluoride concentration in community water and bottled drinking water: a dilemma
      today.
AB  - BACKGROUND: Because of the potential for contamination of municipal water
      supplies, people appear to be turning to alternative sources for their pure
      drinking water. OBJECTIVES: The present study analyzed the fluoride concentration
      in community water and bottled drinking water sold in Faridabad city. METHODS: A
      comparative evaluation of fluoride content in community water supply and bottled
      drinking water was done using ion-selective electrode method. The community water
      samples were collected from six different areas (i.e. north zone, south zone,
      east zone, west zone and central zone) in the city from public health water
      supply taps while bottled drinking water samples were randomly picked from
      grocery shops or supermarkets. RESULTS: The fluoride concentration in the
      community water supply in this study ranges from 0.11 to 0.26 mg/L with mean
      fluoride concentration of 0.17 mg/L. The mean concentration of fluoride in
      bottled drinking water was 0.06 mg/L. The differences observed between mean of
      two water samples was statistically significant. CONCLUSION: The results obtained
      from the present study clearly state that the fluoride concentration was
      insufficient in community water supply from all the areas and also was deficient
      in bottled drinking water sold in Faridabad city. So, Alternative sources of
      fluorides should be supplemented for optimal dental benefits from the use of
      fluoride.

PMID- 24096218
TI  - A comparative study of sexual dysfunction in schizophrenia patients taking
      aripiprazole versus risperidone.
AB  - BACKGROUND: Sexual dysfunction due to antipsychotics is a significant problem
      encountered with first-generation antipsychotics. Even the second-generation
      antipsychotics like risperidone are not free of sexual dysfunction due to its D2
      blocking properties leading to hyperprolactinaemia. Newer antipsychotic
      aripiprazole, partial dopamine agonist, with neutral effect on prolactin level or
      even decreasing it, is associated with avoidance of sexual dysfunction.
      OBJECTIVES: To assess the effect of risperidone and aripiprazole on sexual
      function of schizophrenic patients. METHODS: This was an open-label, cross
      sectional, observational study conducted at College of Medical Sciences,
      Bharatpur. Schizophrenic patients attending OPD and inpatient, taking risperidone
      or aripiprazole for at least two months were included in this study. Forty one
      patients, without chronic medical illness and sexual dysfunction before starting
      drugs, with informed consent were studied during Jan 2012 and Aug 2012. RESULTS:
      Changes in sexual activity was found in 11(55%) of those taking risperidone
      while, only 3(14.3%) had any kind of sexual difficulty. This was statistically
      significant (p=0.006). Majority, 92.7% of the patients did not report about
      changes in sexual activity spontaneously. CONCLUSION: Sexual dysfunction was
      statistically significantly higher in those taking risperidone. Prevalence of
      sexual dysfunction was low with aripiprazole. Except those having poor sexual
      functions due to the drugs, the majority had to be specifically inquired about
      the effects of drug on sex life.

PMID- 24096219
TI  - Cervical epidural anaesthesia with ropivacaine for modified radical mastectomy.
AB  - BACKGROUND: Cervical epidural anaesthesia (CEA) using local anesthetics (LA) is a
      well established technique for the surgeries in the neck, chest and upper arms.
      Recently ropivacaine is introduced with better safety profile. OBJECTIVES: The
      aim was to observe the safety of Cervical epidural anaesthesia as an anaesthetic
      technique and to compare the efficacy of epidural 0.25% bupivacaine with 0.375%
      ropivacaine for radical mastectomies. METHODS: A double blind study was conducted
      on 40 ASA grade I / II females who received CEA with 10 ml of 0.25% of
      bupivacaine +25MUg of fentanyl in group B (n=20) and 10 ml of 0.375% of
      ropivacaine +25MUg of fentanyl in group R (n=20) epidurally. Assessment of the
      block, vital monitoring and complications noted. RESULTS: No significant
      differences observed in the onset of sensory block (5.05 min and 5.4 min in group
      B and R respectively, P>0.05).The mean motor blockade score, time to achieve
      complete blockade and time to grade I motor recovery was significantly longer in
      group B (2.3, 22.5 and 79.5 minutes respectively) as compared to group R (1.5,
      18.3 and 66.3 minutes respectively, P<0.05). Respiratory distress developed in
      two patients of group B that required general anaesthesia (GA) with intubation.
      CONCLUSION: Use of 0.37% ropivacaine is safer than 0.25% bupivacaine for CEA for
      radical mastectomy. It provides good surgical anaesthesia with lesser degree of
      motor blockade and the respiratory effects.

PMID- 24096220
TI  - Lymphocytes protect cortical neurons against excitotoxicity mediated by kainic
      acid, an in vitro model for neurodegeneration.
AB  - BACKGROUND: Neurodegenerative disease is a progressive loss of neurons from the
      central nervous system (CNS). Various conditions have been implicated for such
      conditions including ageing, inflammation, stress and genetic predisposition.
      Recently, studies have linked neurodegeneration with inflammation. Some studies
      have suggested the harmful effect of immune response while others have argued its
      neuroprotective role in neurodegeneration of the CNS. However, the precise role
      of inflammation and immune cells in such condition is still not clear. OBJECTIVE:
      To investigate the role of lymphocytes in neurodegeneration of the CNS and
      determine the underlying mechanism. METHOD: We have used 4-7 days old mouse pups
      (C57Bl6) to prepare organotypic slice cultures which were cultured for 13-15 days
      prior to experiment. To induced cell death kainic acid was used and considered as
      an in vitro model for neurodegeneration. Lymphocytes were obtained from
      peripheral lymph nodes of 5-10 weeks old adult mouse which were used in the
      current study. Propidium iodide was used as a fluorescent dye to determine cell
      death in brain slice cultures. RESULT: Lymphocytes do not induce cell death in
      slice cultures in the absence of any toxic insult whereas, after applying toxic
      insult to the slice cultures using kainic acid, lymphocytes show neuroprotection
      against such insult. Similarly, purified nonactivated and purified activated T
      cells along with T cells depleted lymphocyte preparation also exhibit
      neuroprotection against kainic acid-induced cell death. We further, have
      demonstrated that the observed neuroprotection is contact-independent and soluble
      mediators released from lymphocytes are responsible for the observed
      neuroprotection. Moreover, our study has revealed that soluble mediators
      exhibiting neuroprotection act via astrocytes. CONCLUSION: Lymphocyte
      preparations are neuroprotective and the observed neuroprotection is contact
      independent. Soluble mediators released from lymphocytes are responsible for the
      observed neuroprotection.

PMID- 24096221
TI  - Epidemiological and outcome analysis of orthopedic implants removal in Kathmandu
      University Hospital.
AB  - BACKGROUND: Orthopedic Implant removal is one of the commonly performed elective
      orthopedic surgeries. Implants are generally removed after the purpose of keeping
      implant is solved by healing of the fracture, but there is no consensus whether
      routine implant removal should be a policy for all fractures that were fixed.
      OBJECTIVE: This study aims to analyze the epidemiology and outcome of implant
      removal surgery carried out in the past three years in Kathmandu University
      Hospital. METHODS: Patients who underwent implant removal between 2010 January to
      2012 December constituted the study cohort. Demographic data, indications, types
      of hardware and location of fractures were recorded. Similarly, duration of
      surgery, type of anesthesia and duration of hospital stay were recorded. All the
      patients who had undergone implant removal in this three years period were called
      for follow up examination but those who were not able to come were interviewed on
      telephone. RESULTS: There were 275 implant removals constituting 7.8% of total
      orthopedic operations and 26.3% of fracture fixations. Male to Female ratio was
      189: 86. Pediatric age group (34.5%) had the highest incidence of implant
      removal. Moderate sized implants were the commonest hardwares removed (63.2%).
      Femur (27.3%) followed by radius (26.9%) were the commonest bone for implant
      removal. Average operative time was 47.3 minutes with average hospital inpatient
      stay of 2.6 days. Commonest indication for the implant removal procedure was pain
      (45%). CONCLUSION: Implant removal procedures are one of the most commonly
      performed elective orthopedic surgeries. Though, after orthopedic implants
      removal, pain relief can be expected but it is not so predictive and hence
      patient should be well counseled before and the indications for implant removal
      has to be evaluated for better patient satisfaction and safety.

PMID- 24096222
TI  - Post-operative drop in hemoglobin and need of blood transfusion in cesarean
      section at Dhulikhel Hospital, Kathmandu University Hospital.
AB  - BACKGROUND: Cesarean section has been identified as one of the commonest
      indication for blood transfusion in obstetric practice because it involves risk
      of major intra-operative blood loss. Different figures varying from less than 500
      ml to more than 1000 ml have been quoted as estimated blood loss associated with
      caesarean section. There is also a wide variation in blood ordering practices for
      this surgery. OBJECTIVE: The objective of this study is to evaluate the blood
      ordering practice and transfusion for cesarean sections at our institute, to see
      post-operative drop in hemoglobin and hematocrit and to correlate those
      parameters with the duration between uterine incision and repair. METHODS: In
      this prospective observational study, non-randomised purposive sample was taken
      from 121 ladies who underwent elective and emergency cesarean section at the
      department of obstetrics of Dhulikhel Hospital-Kathmandu University Hospital.
      Post-cesarean drop in hemoglobin and hematocrit and their relation with duration
      of uterine manipulation was calculated. Cross-match to transfusion (C/T ratio)
      ratio, transfusion probability (%T) and transfusion index (Ti) were also
      calculated. RESULTS: Most frequent blood group was found to be O positive (38%)
      among those ladies. Average post-cesarean drop in hemoglobin was 1.52+/-1.27
      gm/dl and drop in haematocrit was 5.49+/-4.1%. Post-operative drop in hemoglobin
      and haematocrit had weak and positive linear relation with duration between
      uterine incision and repair. Cross-match to transfusion ratio was 1, transfusion
      probability 100% and transfusion index was 2. CONCLUSION: There is no need of
      routine cross-matching of blood for cesarean section. Only grouping with
      confirmation of availability should be done for emergency situation.

PMID- 24096223
TI  - A convenient way to do valgus osteotomy for neglected fracture neck of femur.
AB  - BACKGROUND: Neglected fracture of neck of femur in young adults is a major
      problem in developing countries. Existing treatment options varies from osteotomy
      to various graft techniques (muscle pedicle, vascularized and nonvascularized
      fibula etc.). There is paucity of literature regarding the use of double angle
      barrel plate and hip screw in such cases. We conducted a prospective longitudinal
      observational study with displaced, neglected fracture neck of femur in young
      adults and compared the results with literature. OBJECTIVES: The aim of this
      study was to determine feasibility and effectiveness of 120 degrees  double angle
      barrel plate and hip screw fixation in neglected fracture neck of femur.
      Effectiveness of fixed 30 degree closed wedge osteotomy in neglected fracture
      neck of femur. METHODS: Thirty cases of neglected (more than three weeks) femoral
      neck fracture (Pauwel II and III) of age 20-60 years were included in the study
      conducted at Postgraduate Institute Of Medical Education and Research, Dr. Ram
      Manohar Lohia Hospital, New Delhi, India in year 2004-06. Average age of the
      patient was 35.4 years (range, 22yrs-55yrs). In all cases internal fixation was
      done by 120 degrees  double angle barrel plate and hip Screw. At the end of
      follow-up, results were evaluated according to Askin Bryan Criteria and Harris
      hip score. RESULTS: Union was achieved in 28 of 30 patients. Two patients that
      went into nonunion were later treated with hemireplacement arthroplasty.
      According to Askin Bryan Criteria at the end of study, 35% patients had excellent
      results, 50% patients had good results. Minimum follow-up in our study was 12
      months and maximum was five years. CONCLUSION: This study validates the use of
      double angled screw plate configuration for successful outcome in patients with
      neglected fracture neck of femur. Valgus osteotomy is also technically easy
      operation in hands of average trauma surgeon with the use of a fixed angle plate
      and hip screw.

PMID- 24096224
TI  - A cross-sectional comparison of drinking patterns, alcohol use and related
      medical morbidities in a secondary versus tertiary setting.
AB  - BACKGROUND: Alcohol Dependence exists in different spectrums at different
      settings and associated with various medical morbidities, disability and health
      care utilization costs. OBJECTIVES: To study the drinking patterns, alcohol use
      disorders and alcohol related medical morbidities in patients diagnosed with
      Alcohol Dependence Syndrome (ADS) and attending out / in-patient psychiatry
      services at secondary and tertiary care centre. METHODS: A cross-sectional
      comparative study was done among the patients diagnosed with ADS attending
      psychiatry services at District hospital, Udupi and Kasturba Hospital, Manipal.
      Serial sampling was done. Patients having any other psychiatric illnesses were
      excluded. The two groups were compared in relation to socio-demographic
      variables, drinking related variables, patterns of drinking and alcohol related
      medical morbidities identified. RESULTS: Significant differences in some socio
      demographic parameters among the patients from the two different treatment
      centers were found with secondary level hospital (N=50) having more illiterate,
      laborers and below the poverty line population in comparison to the tertiary
      level hospital (N=75). Maximum frequency of gastrointestinal morbidities was seen
      in both the hospital population, irrespective of the patterns of drinking.
      CONCLUSION: Alcohol use disorders and alcohol related medical morbidities show
      some variations in their presentations in the different treatment centers.

PMID- 24096225
TI  - Education: the key to curb HIV and AIDS epidemic.
AB  - Overwhelming impact has been established among different aspects and burden of
      incurable HIV and AIDS is increasing day-by-day globally. The aim of this article
      is to discuss the potential benefits and strengths of an education system in the
      absence of remedy and help to develop future strategies. Education has great
      impact on HIV and AIDS and vice-versa. An education plays a vital role to curb
      the transmission of HIV and AIDS thorough capacity building, provides
      information, reduces vulnerability, empowerment, improve life skill, maintain
      equity, reduce dependence, stigma, and discrimination, where are abundance
      foundations for HIV infection. HIV and AIDS has role for devastation of education
      system and level which has great impact on productivity, economic growth, demand,
      supply and daily life of human being. Low and middle income countries needs to be
      improve recording and reporting systems related to impact of HIV and AIDS on
      education. By analyzing preceding evidences, policy makers or governance feels to
      reformulate policies relating to education and health. Evidence based policy and
      program will be more useful to address distressing squall of epidemic. 

PMID- 24096226
TI  - Fenestration of axillary vein by a variant axillary artery.
AB  - Variations of venous pattern in the arm are common. In this case report, we
      present a variation of axillary artery and vein. During routine educational
      dissections of axillary region, it was observed that a fenestrated axillary vein
      was perforated by a variant axillary artery in right arm of an old male cadaver.
      The axillary artery which was fenestrated through axillary vein had only two
      branches arising from its second part and no branches from its remaining distal
      parts. The branches are thoraco-acromial (usual) and another large collateral
      (unusual) branch. This collateral branch is the origin of several important
      arteries as the subscapular, circumflex scapular, posterior circumflex humeral
      and lateral thoracic arteries. We propose to name this artery as collateral
      axillary arterial trunk. The course of this collateral axillary arterial trunk
      and its branches and also clinical significance of this variation are discussed
      in the paper.

PMID- 24096227
TI  - Return of visual acuity to normal in old age.
AB  - Changes occur in our body through out life. Decreased visual acuity is probably
      the most common effect of age-related anatomical and neurological changes in the
      eyes and the visual pathway. However, this case is an exception as at the age of
      75 years, his power of accommodation has returned to normal. The improvement in
      accommodation and visual acuity is hard to explain. Likely explanations given
      need to be further investigated. 

PMID- 24096228
TI  - Terminal bifurcation of the right testicular vein and left testicular arterio
      venous anastomosis.
AB  - The testis is the organ upon which the survival of the human species depends.
      Abnormalities of testicular vessels may lead to loss of gametogenesis and hormone
      production. Reported here is a case of bilateral variations of the testicular
      vessels observed in a male cadaver during the first year MBBS dissection classes.
      The right testicular vein bifurcated into two veins just before its termination
      and both the branches terminated into the inferior vena cava. The left testicular
      artery arose from the abdominal aorta just above the level of origin of the
      inferior mesenteric artery. There was an arterio-venous anastomosis between the
      left testicular vein and the left testicular artery. The arterio-venous
      anastomosis might be functionally important as it can change the quality of the
      blood entering the testis. 

PMID- 24096229
TI  - A multidisciplinary approach in treating a patient with unilateral cleft
      alveolus.
AB  - Any type of aesthetic correction in dental practice is always a challenging task,
      especially when it is complicated with cleft lip and alveolus. Careful
      examination and correct decision making at early stage of treatment and multi
      disciplinary approach is always necessary for long term success. This paper
      described a multidisciplinary approach in managing a 19-year-old female patient
      with unilateral cleft alveolus impacted maxillary canine , missing lateral
      incisor and hypoplastic central incisor by surgical , orthodontic and
      prosthodontic means. The impacted canine was surgically exposed and orthodontic
      traction given to bring it into the normal alignment. The missing lateral incisor
      was replaced by a fixed bridge with a ceramic gingival fixed prosthesis to manage
      alveolar cleft. At the same time the hypoplastic defect of central incisor was
      hidden by the full coverage retainer used for the bridge abutment on the tooth.

PMID- 24096230
TI  - Burning mouth syndrome: an enigmatic disorder.
AB  - Burning mouth syndrome (BMS) is a chronic oral pain or burning sensation
      affecting the oral mucosa, often unaccompanied by mucosal lesions or other
      evident clinical signs. It is observed principally in middle-aged patients and
      postmenopausal women and may be accompanied by xerostomia and altered taste.
      Burning mouth syndrome is characterized by an intense burning or stinging
      sensation, preferably on the tongue or in other areas of mouth. This disorder is
      one of the most common, encountered in the clinical practice. This condition is
      probably of multifactorial origin; however the exact underlying etiology remains
      uncertain. This article discusses several aspects of BMS, updates current
      knowledge about the etiopathogenesis and describes the clinical features as well
      as the diagnosis and management of BMS patients. 

PMID- 24096231
TI  - Gender-based violence: a crucial challenge for public health.
AB  - This article attempts to summarize the situations of gender-based violence, a
      major public health issue. Due to the unequal power relations between men and
      women, women are violated either in family, in the community or in the State.
      Gender-based violence takes different forms like physical, sexual or
      psychological/ emotional violence. The causes of gender-based violence are
      multidimensional including social, economic, cultural, political and religious.
      The literatures written in relation to the gender-based violence are accessed
      using electronic databases as PubMed, Medline and Google scholar, Google and
      other Internet Websites between 1994 and first quarter of 2013 using an internet
      search from the keywords such as gender-based violence, women violence, domestic
      violence, wife abuse, violence during pregnancy, women sexual abuse, political
      gender based violence, cultural gender-based violence, economical gender-based
      violence, child sexual abuse and special forms of gender-based violence in Nepal.
      As GBVs remain one of the most rigorous challenges of women's health and well
      being, it is one of the indispensable issues of equity and social justice. To
      create a gender-based violence free environment, a lot works has to be done.
      Hence, it is suggested to provide assistance to the victims of violence
      developing the mechanism to support them. 

PMID- 24096232
TI  - How I do it? Endoscopic modified inlay butterfly cartilage perichondrium
      myringoplasty.
AB  - Though the microscope has helped a lot in otological surgical procedure but it
      has same optical properties for the last three decades.1 Thus, it has its own
      limitation as it provides a magnified image along a straight line (Fig 1).2
      Meanwhile, the introduction of endoscope in other area of medical field also
      finds its role in ear surgery. Since, the endoscopes have better optics and
      magnification with wide angle of view (Fig 2) due to angled lenses and provide
      the excellent resolution of image. This advantageous factor increases its role in
      surgeries having many difficult anatomic nooks and corners.3 The diagnostic and
      teaching role of endoscope in otological practice has already been proved. Apart
      from that, there are lots of other advantages of endoscope in otological
      surgeries like; antero-inferior recess of external auditory canal, middle ear
      cavity and difficult areas to visualize under microspore like sinus tympani can
      be well visualized.4,5. 

PMID- 24096233
TI  - SLC45A2 mutation frequency in Oculocutaneous Albinism Italian patients doesn't
      differ from other European studies.
AB  - BACKGROUND: Oculocutaneous Albinism (OCA) is a heterogeneous group of inherited
      diseases involving hair, skin and eyes. To date, six forms are recognized on the
      effects of different melanogenesis genes. OCA4 is caused by mutations in SLC45A2
      showing a heterogeneous phenotype ranging from white hair, blue irides and
      nystagmus to brown/black hair, brown irides and no nystagmus. The high clinic
      variety often leads to misdiagnosis. Our aim is to contribute to OCA4 diagnosis
      defining SLC45A2 genetic variants in Italian patients with OCA without any TYR,
      OCA2 and TYRP1 gene defects. MATERIALS AND METHODS: After the clinical diagnosis
      of OCA, all patients received genetic counseling and genetic test. Automatic
      sequencing of TYR, OCA2, and TYRP1 genes was performed on DNA of 117 albino
      patients. Multiplex Ligation-dependent Probe Amplification (MLPA) was carried out
      on TYR and OCA2 genes to increase the mutation rate. SLC45A2 gene sequencing was
      then executed in the patients with a single mutation in one of the TYR, OCA2,
      TYRP1 genes and in the patients, which resulted negative at the screening of
      these genes. RESULTS: SLC45A2 gene analysis was performed in 41 patients and gene
      alterations were found in 5 patients. Four previously reported SLC45A2 mutations
      were found: p.G100S, p.W202C, p.A511E and c.986delC, and three novel variants
      were identified: p.M265L, p.H94D, and c.1156+1G>A. All the alterations have been
      detected in the group of patients without mutations in the other OCA genes.
      CONCLUSIONS: Three new variants were identified in OCA4 gene; the analysis
      allowed the classification of a patient previously misdiagnosed as OA1 because of
      skin and hair pigmentation presence. The molecular defects in SLC45A2 gene
      represent the 3.4% in this cohort of Italian patients, similar to other Caucasian
      populations; our data differ from those previously published by an Italian
      researcher group, obtained on a smaller cohort of patients.

PMID- 24096234
TI  - Association of IL-17A and IL-17F single nucleotide polymorphisms with
      susceptibility to osteoarthritis in a Korean population.
AB  - The damage incurred in osteoarthritis (OA) is mediated by a variety of cytokines,
      growth factors and inflammatory mediators. The importance of the interleukin-17
      (IL-17) family in inflammatory and autoimmune disease is becoming increasingly
      apparent. Microsatellite association mapping reveals a primary osteoarthritis
      susceptibility locus on chromosome 6p12.3-q13. IL-17A and IL-17F genes that
      resided on chromosome 6p12.3-q13 are believed to play an important role in the
      primary OA susceptibility. We investigated the allele and genotype of IL-17A G
      197A and IL-17F T7488C in 302 OA patients and 300 healthy subjects as controls.
      We employed a PCR-SSCP assay to identify the genotypes IL-17A G-197A and IL-17F
      T7488C. For IL-17A G-197A, there were significant differences in frequencies of
      genotype and allele of IL-17A G-197A between OA patients and controls (both
      p<0.0001). For IL-17F T7488C, there were no significant differences in the allele
      frequency and genotype distribution for IL-17F T7488C between OA patients and
      controls (p=0.938 and p=0.1735, respectively). In conclusion, current study
      showed that polymorphism of IL-17A G-197A may be closely associated with
      susceptibility to the development of OA in the Korean population. However, there
      was no relationship between IL-17F T7488C polymorphism and OA susceptibility.

PMID- 24096235
TI  - Effects of Cd & Ni toxicity to Ceratophyllum demersum under environmentally
      relevant conditions in soft & hard water including a German lake.
AB  - Even essential trace elements are phytotoxic over a certain threshold. In this
      study, we investigated whether heavy metal concentrations were responsible for
      the nearly complete lack of submerged macrophytes in an oligotrophic lake in
      Germany. We cultivated the rootless aquatic model plant Ceratophyllum demersum
      under environmentally relevant conditions like sinusoidal light and temperature
      cycles and a low plant biomass to water volume ratio. Experiments lasted for six
      weeks and were analysed by detailed measurements of photosynthetic biophysics,
      pigment content and hydrogen peroxide production. We established that
      individually non-toxic cadmium (3 nM) and slightly toxic nickel (300 nM)
      concentrations became highly toxic when applied together in soft water, severely
      inhibiting photosynthetic light reactions. Toxicity was further enhanced by
      phosphate limitation (75 nM) in soft water as present in many freshwater
      habitats. In the investigated lake, however, high water hardness limited the
      toxicity of these metal concentrations, thus the inhibition of macrophytic growth
      in the lake must have additional reasons. The results showed that synergistic
      heavy metal toxicity may change ecosystems in many more cases than estimated so
      far.

PMID- 24096236
TI  - Cloning and characterization of the retinoic acid receptor-like protein in the
      rock shell, Thais clavigera.
AB  - The organotin compounds have a high affinity for the retinoid X receptor (RXR),
      which is a transcriptional factor activated by retinoids that induce imposex in
      gastropods. However, the molecular mechanisms underlying the regulation of RXR
      and its related genes in gastropods remain unclear. We isolated a retinoic acid
      receptor (RAR)-like cDNA (TcRAR) in the rock shell, Thais clavigera, and examined
      the transcriptional activity of the TcRAR protein by using all-trans retinoic
      acid (ATRA). However, we did not observe any ligand-dependent transactivation by
      this protein. We also examined the transcriptional activity of the TcRAR-ligand
      binding domain fused with the GAL4-DNA binding domain by using retinoic acids,
      retinol, and organotins and again saw no noteworthy transcriptional induction by
      these chemicals. Use of a mammalian two-hybrid assay to assess the interaction of
      the TcRAR protein with the TcRXR isoforms suggested that TcRAR might form a
      heterodimer with the RXR isoforms. The transcriptional activity of domain-swapped
      TcRAR chimeric proteins (the A/B domain of TcRAR combined with the D-F domain of
      human RARalpha) was also examined and found to be ATRA-dependent. These results
      suggest that TcRAR is not activated by retinoic acids, but can form a heterodimer
      with TcRXR isoforms. These data contribute to our understanding of the mechanism
      by which RXR functions in gastropods. 

PMID- 24096237
TI  - Endocrine disruption and oxidative stress in larvae of Chironomus dilutus
      following short-term exposure to fresh or aged oil sands process-affected water.
AB  - Understanding the toxicity of oil sands process-affected water (OSPW) is a
      significant issue associated with the production of oil from the Alberta oil
      sands. OSPW is acutely and chronically toxic to organisms, including larvae of
      Chironomus dilutus. In this study, fresh OSPW ('WIP-OSPW') was collected from the
      West In-Pit settling pond and aged OSPW ('FE5-OSPW') was collected from the FE5
      experimental reclamation pond, both of which are located on the Syncrude Canada
      Ltd. lease site near Fort McMurray, Alberta, Canada. Larvae of C. dilutus were
      exposed to a freshwater control, WIP-OSPW, or FE5-OSPW for 4 or 7 days and
      survival, growth, and markers of oxidative stress and endocrine disruption were
      assessed. Survival was not significantly different among treatment groups.
      Compared to masses of larvae exposed to freshwater, masses of larvae exposed to
      WIP-OSPW were 49% lesser on day 4 and 62% lesser on day 7. However, organisms
      exposed to FE5-OSPW did not have significantly lesser masses than controls.
      Abundances of transcripts of glutathione-s-transferase (gst), catalase (cat), and
      glutathione peroxidase (gpx), which are important for the response to oxidative
      stress, were significantly altered in larvae exposed to WIP-OSPW, but not FE5
      OSPW, relative to controls. Peroxidation of lipids was greater in larvae exposed
      to WIP-OSPW, but not FE5-OSPW. Exposure to fresh OSPW might have caused endocrine
      disruption because abundances of transcripts of the steroid hormone receptors,
      ultraspiricle protein (usp), ecysteroid receptor (esr), and estrogen related
      receptor (err) were greater in larvae exposed to WIP-OSPW for 7 days, but not FE5
      OSPW. These results suggest that lesser growth of larvae of C. dilutus exposed to
      fresh OSPW might be due to oxidative stress and disruption of endocrine
      processes, and that aging of OSPW attenuates these adverse effects. 

PMID- 24096238
TI  - A nanosensor based on quantum-dot haptens for rapid, on-site immunoassay of
      cyanotoxin in environmental water.
AB  - A nanoprobe based on quantum-dot (QD) haptens was synthesized by conjugating
      carboxyl quantum dots with aminoethyl-microcystin (MC)-leucine-arginine (LR). A
      two-alkyl group was introduced to supply a spacer between the QD nanoprobe and
      anti-MC-LR antibody to reduce the steric hindrances of immunoreaction. The sensor
      system based on a portable optofluidic platform exhibited a liner range of 0.10
      4.0 ug/L for MC-LR with a detection limit of 0.03 ug/L. The proposed sensor has
      potential application in the rapid, on-site detection of MC-LR in real water
      samples.

PMID- 24096239
TI  - Broad-spectrum antivirals for the emerging Middle East respiratory syndrome
      coronavirus.
AB  - OBJECTIVES: Middle East respiratory syndrome coronavirus (MERS-CoV) has emerged
      to cause fatal infections in patients in the Middle East and traveler-associated
      secondary cases in Europe and Africa. Person-to-person transmission is evident in
      outbreaks involving household and hospital contacts. Effective antivirals are
      urgently needed. METHODS: We used small compound-based forward chemical genetics
      to screen a chemical library of 1280 known drugs against influenza A virus in
      Biosafety Level-2 laboratory. We then assessed the anti-MERS-CoV activities of
      the identified compounds and of interferons, nelfinavir, and lopinavir because of
      their reported anti-coronavirus activities in terms of cytopathic effect
      inhibition, viral yield reduction, and plaque reduction assays in Biosafety Level
      3 laboratory. RESULTS: Ten compounds were identified as primary hits in high
      throughput screening. Only mycophenolic acid exhibited low EC50 and high
      selectivity index. Additionally, ribavirin and interferons also exhibited in
      vitro anti-MERS-CoV activity. The serum concentrations achievable at therapeutic
      doses of mycophenolic acid and interferon-beta1b were 60-300 and 3-4 times higher
      than the concentrations at which in-vitro anti-MERS-CoV activities were
      demonstrated, whereas that of ribavirin was ~2 times lower. Combination of
      mycophenolic acid and interferon-beta1b lowered the EC50 of each drug by 1-3
      times. CONCLUSIONS: Interferon-beta1b with mycophenolic acid should be considered
      in treatment trials of MERS.

PMID- 24096240
TI  - Influenza vaccination in Korea.

PMID- 24096241
TI  - Men perceive their female partners, and themselves, as more attractive around
      ovulation.
AB  - The purpose of this study was to test whether men perceive changes in their
      female partner's attractiveness as a function of her fertility status. We further
      tested how both male and female self-perception varies in relation to female
      fertility status. This study benefits from the use of transvaginal
      ultrasonography to detect fertility during the regular cycle and the use of a
      within-subjects design in which romantic couples were followed both across the
      cycle and during hormonal contraceptive use. We find that men rated their female
      partner as more attractive near to ovulation (when fertile) as compared to during
      the luteal cycle phase or during hormonal contraceptive use. Moreover, our
      results point to a presently unrecognized negative consequence of hormonal
      contraceptive use on male self-perception, with men rating themselves lower in
      attractiveness when their partner was using hormonal contraceptives than when she
      was regularly cycling. In contrast, there was no difference across measures in
      female self-reported attractiveness. Results are discussed in terms of their
      potential impact on within-couple social dynamics. 

PMID- 24096243
TI  - Kinetic framework of spindle assembly checkpoint signalling.
AB  - The mitotic spindle assembly checkpoint (SAC) delays anaphase onset until all
      chromosomes have attached to both spindle poles. Here, we investigated SAC
      signalling kinetics in response to acute detachment of individual chromosomes
      using laser microsurgery. Most detached chromosomes delayed anaphase until they
      had realigned to the metaphase plate. A substantial fraction of cells, however,
      entered anaphase in the presence of unaligned chromosomes. We identify two
      mechanisms by which cells can bypass the SAC: first, single unattached
      chromosomes inhibit the anaphase-promoting complex/cyclosome (APC/C) less
      efficiently than a full complement of unattached chromosomes; second, because of
      the relatively slow kinetics of re-imposing APC/C inhibition during metaphase,
      cells were unresponsive to chromosome detachment up to several minutes before
      anaphase onset. Our study defines when cells irreversibly commit to enter
      anaphase and shows that the SAC signal strength correlates with the number of
      unattached chromosomes. Detailed knowledge about SAC signalling kinetics is
      important for understanding the emergence of aneuploidy and the response of
      cancer cells to chemotherapeutics targeting the mitotic spindle. 

PMID- 24096244
TI  - Transcatheter aortic valve implantation: patient selection.
AB  - Transcatheter aortic valve implantation (TAVI) is a disruptive technology as it
      satisfies a previously unmet need which is associated with a profound therapeutic
      benefit. In randomized clinical trials, TAVI has been shown to improve survival
      compared with medical treatment among patients considered not suitable candidates
      for surgical aortic valve replacement (SAVR), and to provide similar outcomes as
      SAVR in selected high-risk patients. Currently, TAVI is limited to selected
      elderly patients with symptomatic severe aortic stenosis. As this patient
      population frequently suffers from comorbid conditions, which may influence
      outcomes, the selection of patients to undergo TAVI underlies a complex decision
      process. Several clinical risk score algorithms are routinely used, although they
      fall short to fully appreciate the true risk among patients currently referred
      for TAVI. Beyond traditional risk scores, the clinical assessment by an
      interdisciplinary Heart Team as well as detailed imaging of the aortic valve,
      aortic root, descending and abdominal aorta as well as peripheral vasculature are
      important prerequisites to plan a successful procedure. This review will
      familiarize the reader with the concepts of the interdisciplinary Heart team,
      risk scores as well as the most important imaging algorithms suited to select
      appropriate TAVI patients. 

PMID- 24096242
TI  - The spindle assembly checkpoint works like a rheostat rather than a toggle
      switch.
AB  - The spindle assembly checkpoint (SAC) is essential in mammalian mitosis to ensure
      the equal segregation of sister chromatids. The SAC generates a mitotic
      checkpoint complex (MCC) to prevent the anaphase-promoting complex/cyclosome
      (APC/C) from targeting key mitotic regulators for destruction until all of the
      chromosomes have attached to the mitotic apparatus. A single unattached
      kinetochore can delay anaphase for several hours, but how it is able to block the
      APC/C throughout the cell is not understood. Present concepts of the SAC posit
      that either it exhibits an all-or-nothing response or there is a minimum
      threshold sufficient to block the APC/C (ref. 7). Here, we have used gene
      targeting to measure SAC activity, and find that it does not have an all-or
      nothing response. Instead, the strength of the SAC depends on the amount of MAD2
      recruited to kinetochores and on the amount of MCC formed. Furthermore, we show
      that different drugs activate the SAC to different extents, which may be relevant
      to their efficacy in chemotherapy.

PMID- 24096245
TI  - Role of balloon postdilation following trancatheter aortic valve implantation.
AB  - Paravalvular aortic regurgitation (AR) is a frequent complication following
      transcatheter aortic valve implantation (TAVI) with an incidence of mild to
      moderate AR almost systematically higher than 30%. Moreover, several studies have
      shown that AR has a negative impact on short and mid-term mortality. Balloon
      postdilation has been proposed as an initial periprocedural option for patients
      with paravalvular AR to obtain a better expansion of the stent valve frame and
      potentially reduce the severity of the leak. The aim of this review is to discuss
      the current available literature on balloon postdilation as a treatment of
      paravalvular AR after TAVI, its impact on clinical events and future
      perspectives. 

PMID- 24096246
TI  - Evolution of definitions and understanding of vascular complications related to
      transcatheter aortic valve replacement.
AB  - Vascular complications have emerged as a major clinical challenge during
      transcatheter aortic valve replacement (TAVR). Recent reports demonstrate that
      major vascular complications not only predict major bleeding, transfusions, and
      renal failure, but are also associated with increased mortality. During the early
      development of TAVR, heterogeneous definitions of vascular complications were
      used in the literature. However, the Valve Academic Research Consortium has made
      significant progress in standardizing outcomes definitions in the study of this
      emerging technology. This has resulted in a rapidly expanding body of high
      quality clinical research exploring important outcomes of TAVR, including
      vascular complications. This review seeks to summarize the literature and to
      explore the current state of knowledge with respect to the incidence, predictors,
      clinical impact, and management of vascular complications associated with TAVR. 

PMID- 24096247
TI  - Paravalvular leak after transcatheter aortic valve replacement.
AB  - Paravalvular leak (PVL) is a frequent complication of transcatheter aortic valve
      replacement (TAVR) that occurs at a much higher rate after TAVR than after
      conventional surgical aortic valve replacement. Recent reports indicating that
      PVL may be associated with increased late mortality have raised significant
      concern. However, the heterogeneity of methods for assessing and quantifying PVL,
      in addition to lack of consistency in the timing of this assessment, complicate
      the understanding of its true prevalence, severity, and clinical implications.
      The following review is an effort to consolidate current knowledge in this area
      in order to better understand the incidence, progression, and clinical impact of
      post-TAVR PVL, as well as to focus future research efforts on the assessment,
      prevention, and treatment of this important complication. 

PMID- 24096248
TI  - Mechanical circulatory support with the Impella 5.0 device for postcardiotomy
      cardiogenic shock: a three-center experience.
AB  - AIM: Postcardiotomy cardiogenic shock (PCCS) is associated with high mortality
      rates, despite full conventional treatment. Although the results of treatment
      with surgically implantable ventricular assist devices have been encouraging, the
      invasiveness of this treatment limits its applicability. Several less invasive
      devices have been developed, including the Impella system. The objective of this
      study was to describe our three-center experience with the Impella 5.0 device in
      the setting of PCCS. METHODS: From January 2004 through December 2010, a total of
      46 patients were diagnosed with treatment-refractory PCCS and treated with the
      Impella 5.0 percutaneous left ventricular assist device at three european heart
      centers. Baseline and follow-up characteristics were collected retrospectively
      and entered into a dedicated database. RESULTS: Within the study cohort of 46
      patients, mean logistic and additive EuroSCORES were 24 +/- 19 and 10 +/- 4. The
      majority of patients underwent coronary artery bypass grafting (48%) or combined
      surgery (33%). Half of all patients had been treated with an intra-aortic balloon
      pump before 5.0-implantation, 1 patient had been treated with an Impella 2.5
      device. All patients were on mechanical ventilation and intravenous inotropes.
      The Kaplan-Meier estimate of overall 30-day survival was 39.5%. CONCLUSION:
      Thirty-day survival rates for patients with PCCS, refractory to aggressive
      conventional treatment and treated with the Impella 5.0 device, are comparable to
      those reported in studies evaluating surgically implantable VADs, whereas the
      Impella system is much less invasive. Therefore, mechanical circulatory support
      with the Impella 5.0 device is a suitable treatment modality for patients with
      severe PCCS.

PMID- 24096249
TI  - Self-expanding intracoronary stents in the treatment of coronary artery disease:
      new developments and future directions.
AB  - The first stent implanted in the human coronary circulation was a self-expandable
      (SE) stent and was introduced almost simultaneously with the first balloon
      expandable (BE) stents in the late 1980s. Nowadays, the majority of the available
      stents are delivered by balloon expansion. While BE stents reach their final size
      at the time of implantation, the SE stent continues to enlarge days to weeks
      after implantation. Potential advantages of the self-expandable and self-apposing
      properties of nitinol stents, a super-elastic metallic alloy of nickel and
      titanium, could be reduction of acute and late acquired stent malapposition with
      a subsequently decreased risk of target vessel restenosis. Several nitinol stents
      have been developed and clinically evaluated and are now in use in daily clinical
      practice. However, it is important to further improve and optimize the SE stent
      design and apply newer strategies to the development of next generation SE
      stents. The present review will provide an overview of the development of these
      devices and the currently available clinical evidence of the contemporary SE
      stents. 

PMID- 24096250
TI  - Biodegradable-polymer-based drug-eluting stent for left main coronary artery
      disease.
AB  - Percutaneous coronary interventions (PCI) have gained widespread acceptation
      among cardiologists and among the general population for a variety of clinical
      indications, comprising from stable angina to ST-elevation acute myocardial
      infarction, due to the undisputed clinical benefit they provide and to their
      large availability and accessibility. Nonetheless PCI in the left main coronary
      artery (LMCA) is still controversial. Traditionally the revascularization of the
      LMCA has been one of those exceptions in which surgery was preferred to PCI,
      although PCI still found a slot in non-surgically-suitable cases or as bailout
      intervention. Some evidence has been recently generated, that challenges this
      traditional approach, and also about the clinical advantages of new-generation
      intracoronary devices, among them the drug-eluting stents with biodegradable
      polymers in abluminal coating. This scenario opens new horizons for the treatment
      of LMCA disease, in which a more prominent role of PCI can be anticipated. 

PMID- 24096251
TI  - How to optimize the percutaneous treatment of bifurcated lesions: dedicated
      stents vs. provisional stenting.
AB  - Although provisional T-stenting with stenting of the main branch and optional
      side branch stenting is nowadays the default strategy generally preferred for
      simple bifurcation lesions, percutaneous coronary intervention (PCI) of complex
      true bifurcation lesions remains a difficult task to achieve also with modern
      second generation drug eluting stents. Treatment of complex bifurcational lesions
      is not only more time consuming but can lead to significantly higher rate of
      periprocedural myocardial infarction and late estenosis, stent thrombosis and
      target lesion revascularization. These clinical complications may be at least in
      part be due to the fact that current bifurcation techniques often fail to ensure
      continuous stent coverage of the SB ostium and the bifurcation branches and often
      leave a significant number of malapposed struts. Struts left unapposed in the
      lumen are not efficient for drug delivery to the vessel wall, disturb blood flow
      and may increase the risk of restenosis and stent thrombosis. This article
      summarises the various techniques of bifurcation stenting, highlighting their
      relative merits and disadvantages. In addition, the role of newer dedicated
      bifurcation stent devices, as well as the role of imaging in guiding optimal
      stent deployment will be discussed.

PMID- 24096252
TI  - Prediction of incident hypertension. Health implications of data mining in the
      'Big Data' era.

PMID- 24096253
TI  - Ambulatory blood pressure in children: confidence and wisdom.

PMID- 24096254
TI  - Genetic mechanisms of vascular and renal damage.

PMID- 24096255
TI  - Salt and obesity revisited.

PMID- 24096256
TI  - The 'renaissance era' of sympathomodulatory interventions in the treatment of
      hypertension-related congestive heart failure.

PMID- 24096257
TI  - Prevalence of arterial hypertension in Serbia: PAHIS study.
AB  - BACKGROUND: Arterial hypertension (AH) is the most common cardiovascular disease
      risk factor, affecting between 30 and 50% of the adult population in developed
      countries. A steady increase of the prevalence of AH by about 60% is expected by
      year 2025. METHODS: Serbian Society of Hypertension conducted a prevalence study
      from February to May 2012 on a sample of 3878 adult respondents. The study
      included 2066 women (53.3%) and 1812 men (46.7%). Average age was 48.89 +/- 17.48
      years. Most participants resided in urban areas (2956 people, 76.2%), whereas 922
      resided in rural areas (23.8%). RESULTS: The prevalence of AH in Serbia is 42.7%.
      Hypertension is more frequently diagnosed among women (53.3%), than among men
      (46.7%). One thousand, four hundred and twelve respondents were previously
      diagnosed and treated for hypertension. The estimated awareness of the presence
      of AH was 42.99% (i.e. 40.00% among male and 45.41% among female participants).
      Out of all diagnosed cases of hypertension, 390 persons (27.7%) have well
      regulated blood pressure values, whereas 1022 persons (72.3%) do not have their
      blood pressure under control. CONCLUSION: Serbia belongs to countries with a high
      prevalence of AH. A poor control of AH may be explained in view of socioeconomic
      problems. High prevalence of AH may indicate a remarkably high cardiovascular
      disease mortality in Serbia.

PMID- 24096258
TI  - Acute effects of red wine on cytochrome P450 eicosanoids and blood pressure in
      men.
AB  - OBJECTIVE: The vasodilation accompanying acute alcohol ingestion is hard to
      reconcile with the strong evidence linking chronic alcohol consumption with
      hypertension. Cytochrome P450 (CYP450) eicosanoids derived from arachidonic acid
      include vasodilator epoxyeicosatrienoic acids (EETs) and the vasoconstrictor 20
      hydroxyeicosatrienoic acid (20-HETE). This study aimed to examine the
      relationship between CYP450 eicosanoids and blood pressure (BP), and compared the
      effect of single session of drinking red wine with de-alcoholized red wine (DRW)
      or water over 24 h. METHODS: Twenty-five normotensive men were randomly assigned
      to drink either 375 ml of red wine (41 g of alcohol) or the equivalent volume of
      DRW or water, with a light meal on 3 separate days. Ambulatory BP and heart rate
      were measured over 24 h. Blood samples were obtained before and 2, 4 and 24 h
      after beverage consumption. RESULTS: Blood pressure fell in the first 4 h after
      red wine consumption (P = 0.001), but was significantly higher after 20 h (P =
      0.037). Plasma 20-HETE fell in the 2 h after consumption of all beverages, but
      over the 24-h period was relatively higher after red wine consumption (P =
      0.025). The largest difference in 20-HETE was 2 h after consuming red wine and
      coincided with the highest blood alcohol level. There were no significant effects
      of red wine on plasma EETs. CONCLUSION: Acute consumption of alcohol as red wine
      results in a relative increase in plasma levels of the vasoconstrictor 20-HETE
      over 24 h without affecting EETs, and may contribute to the BP elevation that
      associates with a binge drinking pattern or be a homeostatic response to the
      acute fall in BP induced by alcohol.

PMID- 24096259
TI  - Prevalence and factors related to urinary albumin excretion in obese youths.
AB  - OBJECTIVES: The aim of the present study is to assess whether obesity is
      associated with urinary albumin excretion and what the main determinants are.
      METHODS: One hundred and thirty-four obese white children and adolescents of both
      sexes, ranging from 9 to 18 years of age (mean age 12.6 +/- 2.0), were included
      in the study. Obesity was defined on the basis of a threshold BMI z-score of more
      than 2 (Cole's LMS method) and overweight with a BMI from the 85th to 95th
      percentile. Office blood pressure was measured using a mercury sphygmomanometer.
      Urinary albumin excretion was measured in the first voiding urine of the morning
      and expressed in albumin/creatinine ratio in mg/g. Reproducibility of the urinary
      albumin excretion was studied by the Bland and Altman technique in a subgroup.
      Triglycerides, uric acid, fasting glucose and insulin were measured and the
      homeostatic model assessment (HOMA) index was calculated. RESULTS: The prevalence
      of microalbuminuria was 2.4%. No differences in the prevalence of
      microalbuminuria were observed when the different groups of obesity degree were
      compared (0, 2.2 and 0% in overweight, moderate and severe obese, respectively).
      A significant relationship emerged between the Log urinary albumin excretion and
      BMI z-score, waist circumference, Log triglycerides, fasting insulin and HOMA
      index, adjusted by age and sex. In a multiple regression analysis, the main
      determinants of Log urinary albumin excretion were sex, waist circumference and
      Log triglycerides. In 17% of the individuals who fulfil criteria for metabolic
      syndrome, urinary albumin excretion was significantly higher than those without.
      CONCLUSION: The prevalence of elevated urinary albumin excretion is not prominent
      in obese children, and when it is increased, it depends mainly on metabolic
      factors.

PMID- 24096260
TI  - Moxonidine-induced central sympathoinhibition improves prognosis in rats with
      hypertensive heart failure.
AB  - OBJECTIVES: Enhanced central sympathetic outflow is an indicator of the prognosis
      of heart failure. Although the central sympatholytic drug moxonidine is an
      established therapeutic strategy for hypertension, its benefits for hypertensive
      heart failure are poorly understood. In the present study, we investigated the
      effects of central sympathoinhibition by intracerebral infusion of moxonidine on
      survival in a rat model of hypertensive heart failure and the possible mechanisms
      involved. METHODS AND RESULTS: As a model of hypertensive heart failure, we fed
      Dahl salt-sensitive rats an 8% NaCl diet from 7 weeks of age.
      Intracerebroventricular (ICV) infusion of moxonidine (moxonidine-ICV-treated
      group [Mox-ICV]) or vehicle (vehicle-ICV-treated group [Veh-ICV]) was performed
      at 14-20 weeks of age, during the increased heart failure phase. Survival rates
      were examined, and sympathetic activity, left ventricular function and
      remodelling, and brain oxidative stress were measured. Hypertension and left
      ventricular hypertrophy were established by 13 weeks of age. At around 20 weeks
      of age, Veh-ICV rats exhibited overt heart failure concomitant with increased
      urinary norepinephrine (uNE) excretion as an index of sympathetic activity,
      dilated left ventricle, decreased percentage fractional shortening, and
      myocardial fibrosis. Survival rates at 21 weeks of age (n = 28) were only 23% in
      Veh-ICV rats, and 76% (n = 17) in Mox-ICV rats with concomitant decreases in uNE,
      myocardial fibrosis, collagen type I/III ratio, brain oxidative stress, and
      suppressed left ventricular dysfunction. CONCLUSION: Moxonidine-induced central
      sympathoinhibition attenuated brain oxidative stress, prevented cardiac
      dysfunction and remodelling, and improved the prognosis in rats with hypertensive
      heart failure. Central sympathoinhibition can be effective for the treatment of
      hypertensive heart failure.

PMID- 24096261
TI  - Opinions on the new blood pressure target in chronic kidney disease recommended
      by 2013 ESH/ESC guidelines for the management of arterial hypertension.

PMID- 24096262
TI  - Reply to blood pressure target in chronic kidney disease.

PMID- 24096263
TI  - Sex differences in effects of valsartan administration on cardiovascular outcomes
      in hypertensive patients: findings from the Jikei Heart Study: Retraction.

PMID- 24096265
TI  - MicroRNA-29a ameliorates glucocorticoid-induced suppression of osteoblast
      differentiation by regulating beta-catenin acetylation.
AB  - Excess glucocorticoid treatment induces loss of osteoblast differentiation. Post
      translational modification of beta-catenin reportedly regulates osteogenic
      activities in bone cells. This study was undertaken to test whether miR-29a
      signaling regulates the acetylation status of beta-catenin in the glucocorticoid
      mediated osteoblast dysfunction. Murine osteoblast cultures were incubated under
      osteogenic conditions with or without supraphysiological glucocorticoid, miR-29a
      precursor, antisense oligonucleotides or histone deacetylase 4 (HDAC4) RNA
      interferences. Osteoblast differentiation was determined by alkaline phosphatase
      activity, calcium deposition, and von Kossa stain. beta-Catenin acetylation and
      miR-29a transcription were detected by immunoblotting, chromatin
      immunoprecipitation and quantitative PCR. Protein interaction was detected by
      fluorescence protein ligation assay. Supraphysiological glucocorticoid treatment
      repressed osteoblast differentiation and induced loss of miR-29a expression and
      acetylated beta-catenin levels in osteoblast cultures. Gain of miR-29a function
      attenuated the deleterious effects of glucocorticoid on osteogenic gene
      expression and mineralized nodule formation, whereas knockdown of miR-29a
      signaling accelerated loss of osteoblast differentiation capacity. miR-29a
      reduced HDAC4 signaling and attenuated the glucocorticoid-mediated beta-catenin
      deacetylation and ubiquitination and restored nuclear beta-catenin levels.
      Glucocorticoid-induced loss of miR-29a signaling occurred through transcriptional
      and translational regulation. Interruption of HDAC4 signaling attenuated the
      glucocorticoid-induced hypoacetylation of histone H3 at lysine 9 (H3K9Ac) and
      restored the enrichment of H3K9Ac in miR-29a proximal promoter region and miR-29a
      transcription in cell cultures. Taken together, excess glucocorticoid-induced
      loss of miR-29a signaling accelerates beta-catenin deacetylation and
      ubiquitination that impairs osteogenic activities of osteoblast cultures. miR-29a
      and HDAC4 reciprocal regulation of H3K9 acetylation contributes to the
      acetylation status of beta-catenin and miR-29a expression. Enhancement of miR-29a
      signaling is an alternative strategy for protecting against the adverse actions
      of excess glucocorticoid on differentiation capacity of osteogenic cells. 

PMID- 24096266
TI  - Early enteral nutrition in patients with hemodynamic failure following cardiac
      surgery.
AB  - BACKGROUND: Enteral nutrition (EN) is controversial in patients with circulatory
      compromise. This study assesses the feasibility and safety of EN given early
      after cardiac surgery in patients with hemodynamic failure. METHODS: Prospective
      observational study conducted in a surgical intensive care unit (ICU) of a
      tertiary hospital over 17 months. INCLUSION CRITERIA: Cardiac surgery patients
      with hemodynamic failure (dependence on 2 or more vasoactive drugs and/or
      mechanical circulatory support) requiring more than 24 hours of mechanical
      ventilation. Variables Examined: Descriptive data, daily hemodynamic data, and
      variables related to the efficacy and safety of EN. EN was performed according to
      our EN protocol. RESULTS: Of 642 patients admitted to the ICU, 37 (5.8%) met the
      inclusion criteria. Of these, 11 (29.7%) required mechanical circulatory support,
      and 25 (68.0%) met the criteria for early multiorgan dysfunction. Mortality was
      13.5%. Mean EN duration was 12.3 days (95% confidence interval [CI], 9.6-15.0).
      The mean EN diet volume delivered/patient/d was 1199 mL (95% CI, 1118.7-1278.8),
      and mean EN energy delivered/patient/d was 1228.4 kcal (95% CI, 1145.8-1311). The
      set energy target was achieved in 15 patients (40.4%). The most common EN-related
      complication was constipation. No case of mesenteric ischemia was detected.
      CONCLUSIONS: Our findings indicate that early EN is feasible in this type of
      patients and not associated with serious complications. However, it is difficult
      to attain an appropriate energy target by EN alone. These observations point to a
      need for monitoring of daily energy delivery and balance, as well as careful
      monitoring of warning signs of intestinal ischemia.

PMID- 24096267
TI  - Two cases of recurrent ovarian clear cell carcinoma treated with sorafenib.
AB  - Sorafenib is an oral multikinase inhibitor targeting Raf and other kinases. The
      anti-tumor effect of sorafenib is thought to be mediated through its inhibition
      of the RAS-Raf-Erk pathway, as well as its inhibition of VEGFR and PDGFR.
      Sorafenib has been effective at treating patients with renal cell carcinoma
      (RCC). Ovarian clear cell carcinoma (OCCC) is a chemoresistant subtype of ovarian
      cancer. OCCC is represented by cells with clear cytoplasm that resemble those
      observed in RCC. Using a microarray database, the gene expression profile of OCCC
      was similar to that of RCC. The effects of sorafenib against human OCCC are
      unknown. Therefore, we used sorafenib to treat two patients with recurrent
      chemoresistant OCCC, and observed good effect in both of them without severe side
      effects. We believe that sorafenib is an effective agent against OCCC. Given the
      chemoresistant nature of this tumor, this drug appears to be very valuable. 

PMID- 24096268
TI  - Response to comment on: Dysregulated expression of T cell immunoglobulin and
      mucin domain 3 is associated with the disease severity and the outcome of
      patients with spontaneous intracerebral hemorrhage.

PMID- 24096269
TI  - Rapid sequencing of influenza A virus vRNA, cRNA and mRNA non-coding regions.
AB  - Characterizing the genomic sequences of influenza A viruses is important for
      pathophysiological and evolutionary studies. Noncoding regions (NCR) of influenza
      A virus have been shown to play critical roles in replication and transcription
      but their sequences are infrequently determined. In this study, a method
      employing poly(A) addition and SMART (switching mechanism at 5' end of RNA
      transcript) technology is described for directly determining and discriminating
      both NCR ends of viral RNA (vRNA), complementary RNA (cRNA), or NCR and cap
      sequences from viral mRNA. This modified method may also be used to characterize
      the NCRs of influenza A virus samples in which the RNA has been degraded. 

PMID- 24096270
TI  - Rapid molecular detection of Lujo virus RNA.
AB  - Lujo virus is an emerging arenavirus circulating in Southern Africa. Although to
      date there has only been a single outbreak of the novel haemorrhagic disease
      resulting from human infection with this virus, the case-fatality rate of exposed
      individuals, including nosocomial transmission, was 80%. The ability to identify
      viral haemorrhagic fevers accurately, especially those capable of nosocomial
      transmission, is of critical importance. Timely identification of these diseases
      allow medical professionals to isolate patients and implement barrier nursing
      techniques in order to prevent onward transmission of the virus. While rapid
      diagnostic methods are published for most viral haemorrhagic fevers, at present
      there are no such virus specific protocols for Lujo haemorrhagic fever. This
      report details the first set of diagnostic molecular assays designed to identify
      Lujo viral RNA rapidly, and demonstrates the potential functionality of these
      assays for use in the clinical setting. Although these assays have been designed
      and validated against a solitary isolate of Lujo virus, this represents the
      entirety of strains detected to date, and offer quick, cheap and easy methods for
      use in diagnostic laboratories. 

PMID- 24096271
TI  - Immunochromatographic test for detection of adenovirus from respiratory samples:
      is it a real solution for pediatric emergency department?
AB  - Rapid diagnosis of adenoviral respiratory infections is required in order to
      decide optimal treatment strategies. The adenovirus antigen immunochromatography
      Adeno Respiratory Card Letitest (Leti diagnostics, Barcelona, Spain), was
      evaluated versus the shell-vial culture and multiplex PCR (Clart Pneumovir
      Version 3.0, Genomica, Madrid, Spain), in nasopharyngeal washes and oropharyngeal
      swabs specimens from subjects with respiratory tract infections. Between April
      2011 and November 2012, 224 patients were included. The IC Adeno Respiratory Card
      Letitest was positive for 77.9% (74 of 95) of patients diagnosed at bedside.
      Using multiplex-PCR as the reference standard, the overall sensitivity was 77.9%
      and the specificity was 73.6%. Taking shell-viral culture as the reference
      method, the Adeno Respiratory Card Letitest (Leti diagnostics, Barcelona, Spain)
      sensitivity and specificity values were 80.0% and 60.9%, respectively. Using RT
      PCR (Clart Pneumovir Version 3.0, Genomica, Madrid, Spain) as the reference
      standard, the viral culture sensitivity was 53.2% and the specificity was 100%.
      The Adeno Respiratory Card Letitest (Leti diagnostics, Barcelona, Spain) assay
      could be a simple and rapid method for antigenic detection of adenovirus in
      pediatric respiratory samples although it would be necessary to improve the
      specificity and sensitivity of the test. 

PMID- 24096272
TI  - Effect of magnetic dipolar interactions on nanoparticle heating efficiency:
      implications for cancer hyperthermia.
AB  - Nanostructured magnetic systems have many applications, including potential use
      in cancer therapy deriving from their ability to heat in alternating magnetic
      fields. In this work we explore the influence of particle chain formation on the
      normalized heating properties, or specific loss power (SLP) of both low-
      (spherical) and high- (parallelepiped) anisotropy ferrite-based magnetic fluids.
      Analysis of ferromagnetic resonance (FMR) data shows that high particle
      concentrations correlate with increasing chain length producing decreasing SLP.
      Monte Carlo simulations corroborate the FMR results. We propose a theoretical
      model describing dipole interactions valid for the linear response regime to
      explain the observed trends. This model predicts optimum particle sizes for
      hyperthermia to about 30% smaller than those previously predicted, depending on
      the nanoparticle parameters and chain size. Also, optimum chain lengths depended
      on nanoparticle surface-to-surface distance. Our results might have important
      implications to cancer treatment and could motivate new strategies to optimize
      magnetic hyperthermia. 

PMID- 24096273
TI  - Importance of IdoA and IdoA(2S) ring conformations in computational studies of
      glycosaminoglycan-protein interactions.
AB  - Glycosaminoglycans (GAGs) interact with chemokines and growth factors in the
      extracellular matrix and, therefore, mediate cell communication processes.
      Heparin is one of the most studied GAGs, for which many experimental structures
      of its complexes with proteins are available. One of the monosaccharide
      components of heparin, sulfated iduronic acid (IdoA(2S)), is observed to adopt
      both (1)C4 and (2)S0 ring conformations. Despite the biological relevance of the
      sugar ring conformations for heparin-protein interactions, it is very challenging
      to take into account the conformational space of IdoA(2S) sugar ring for
      computational studies. Therefore, instead of systematically analyzing several
      ring conformations, which represents a combinatorial problem for a periodic
      heparin molecule, often only one ring conformation is taken into account. Here,
      we use docking and molecular dynamics (MD) to estimate how crucial this
      assumption could be for the conclusions being made in computational studies of
      heparin-protein interactions. We show that both docking solutions and free energy
      calculations from MD simulations are significantly affected by the conformations
      adopted by IdoA and IdoA(2S) rings. Therefore, in the application of
      computational approaches to heparin-protein systems the ring conformations should
      be treated properly to avoid misleading conclusions. 

PMID- 24096274
TI  - Structure of the O-polysaccharide of Pseudomonas mandelii CYar1 containing 3,6
      dideoxy-4-C-[(S)-1-hydroxyethyl]-D-xylo-hexose (yersiniose A).
AB  - The O-polysaccharide isolated by mild acid hydrolysis of the lipopolysaccharide
      of Pseudomonas mandelii CYar1 was studied by sugar analysis and 1D and 2D (1)H
      and (13)C NMR spectroscopies. The following structure of the O-polysaccharide was
      established: 

PMID- 24096275
TI  - Clostridium perfringens sepsis following a molar pregnancy.
AB  - Clostridium perfringens sepsis is rare since the legalization of abortion in
      1973. This is a 49 year old female who developed clostridial sepsis after suction
      dilation and curettage for a molar pregnancy. A hysterectomy was performed after
      prompt recognition, and the patient survived. 

PMID- 24096276
TI  - The contribution of genetic and environmental factors to the duration of
      pregnancy.
AB  - This review describes how improvements in biometric-genetic studies of twin
      kinships, half-sibships, and cousinships have now demonstrated a sizeable fetal
      genetic and maternal genetic contribution to the spontaneous onset of labor. This
      is an important development because previous literature for the most part reports
      only an influence of the maternal genome. Current estimates of the percent of
      variation that is attributable to fetal genetic factors range from 11-35%; the
      range for the maternal genetic contribution is 13-20%. These same studies
      demonstrate an even larger influence of environmental sources over and above the
      influence of genetic sources and previously identified environmental risk
      factors. With these estimates in hand, a major goal for research on pregnancy
      duration is to identify specific allelic variation and environmental risk to
      account for this estimated genetic and environmental variation. A review of the
      current literature can serve as a guide for future research efforts.

PMID- 24096278
TI  - Immobilization of horseradish peroxidase on electrospun microfibrous membranes
      for biodegradation and adsorption of bisphenol A.
AB  - Horseradish peroxidase (HRP) from roots of horseradish (Amoracia rusticana) was
      successfully immobilized on novel enzyme carriers, poly(methyl methacrylate-co
      ethyl acrylate) (PMMA CEA) microfibrous membranes, and used for removal of
      bisphenol A from water. PMMA CEA fibrous membranes (PFM) with fiber diameters of
      300-500 nm, were fabricated by electrospinning. HRP was covalently immobilized on
      the surface of microfibers previously activated by polyethylenimine and
      glutaraldehyde. HRP loading reached 285 mg/g, and enzyme activity was 70% of free
      HRP after immobilization. Both stabilities and reusability of HRP were greatly
      improved after immobilization. After six repeated runs, immobilized HRP retained
      about 50% of its initial activity. Immobilized HRP exhibited significantly higher
      removal efficiency for bisphenol A (BPA) in 3h (93%) compared with free HRP (61%)
      and PFM alone (42%). The high BPA removal can be resulted by improvement of
      catalytic activity of immobilized HPR with adsorption on modified PMMA CEA
      support.

PMID- 24096277
TI  - Efficient succinic acid production from lignocellulosic biomass by simultaneous
      utilization of glucose and xylose in engineered Escherichia coli.
AB  - To enhance succinic acid formation during xylose fermentation in Escherichia
      coli, overexpression of ATP-forming phosphoenolpyruvate carboxykinase (PEPCK)
      from Bacillus subtilis 168 in an ldhA, pflB, and ppc deletion strain resulted in
      a significant increase in cell mass and succinic acid production. However, BA204
      displays a low yield of glucose fermentation and sequential glucose-xylose
      utilization under regulation by the phosphotransferase system (PTS). To improve
      the capability of glucose fermentation and simultaneously consume sugar mixture
      for succinic acid production, a pflB, ldhA, ppc, and ptsG deletion strain
      overexpressing ATP-forming PEPCK, named E. coli BA305, was constructed. As a
      result, after 120 h fed-batch fermentation of sugarcane bagasse hydrolysate, the
      dry cell weight and succinic acid concentration in BA305 were 4.58 g L(-1) and
      39.3 g L(-1), respectively.

PMID- 24096279
TI  - Experimental and theoretical characterization of microbial bioanodes formed in
      pulp and paper mill effluent in electrochemically controlled conditions.
AB  - Microbial bioanodes were formed in pulp and paper effluent on graphite plate
      electrodes under constant polarization at -0.3 V/SCE, without any addition of
      nutriment or substrate. The bioanodes were characterized in 3-electrode set-ups,
      in continuous mode, with hydraulic retention times from 6 to 48 h and inlet COD
      from 500 to 5200 mg/L. Current densities around 4A/m(2) were obtained and
      voltammetry curves indicated that 6A/m(2) could be reached at +0.1 V/SCE. A
      theoretical model was designed, which allowed the effects of HRT and COD to be
      distinguished in the complex experimental data obtained with concomitant
      variations of the two parameters. COD removal due to the electrochemical process
      was proportional to the hydraulic retention time and obeyed a Michaelis-Menten
      law with respect to the COD of the outlet flow, with a Michaelis constant KCOD of
      400mg/L. An inhibition effect occurred above inlet COD of around 3000 mg/L.

PMID- 24096280
TI  - Enhancing methane production of Chlorella vulgaris via thermochemical
      pretreatments.
AB  - To enhance the anaerobic digestion of Chlorella vulgaris, thermochemical
      pretreatments were conducted. All pretreatments markedly improved solubilisation
      of carbohydrates. Thermal treatments and thermal treatments combined with alkali
      resulted in 5-fold increase of soluble carbohydrates while thermal treatment with
      acid addition enhanced by 7-fold. On the other hand, proteins were only
      solubilized with thermo-alkaline conditions applied. Likewise, all the
      pretreatments tested improved methane production. Highest anaerobic digestion was
      accomplished by thermal treatment at 120 degrees C for 40 min without any
      chemical addition. As a matter of fact, hydrolysis constant rate was doubled
      under this condition. According to the energetic analysis, energy input was
      higher than the extra energy gain at the solid concentration employed.
      Nevertheless, higher biomass organic load pretreatment may be an option to
      achieve positive energetic balances.

PMID- 24096281
TI  - Removal and fate of endocrine disruptors chemicals under lab-scale postreatment
      stage. Removal assessment using light, oxygen and microalgae.
AB  - The aim of this study was to assess the effect of light, oxygen and microalgae on
      micropollutants removal. The studied micropollutants were 4-(1,1,3,3
      tetramethylbutyl)phenol (OP), technical-nonylphenol (t-NP), 4-n-nonylphenol (4
      NP), Bisphenol-A (BPA). In order to study the effect of the three variables on
      the micropollutants removal, a factorial design was developed. The experiments
      were carried out in four batch reactors which treated the effluent of an
      anaerobic membrane bioreactor. The gas chromatography mass spectrometry was used
      for the measurement of the micropollutants. The results showed that light, oxygen
      and microalgae affected differently to the degradation ratios of each
      micropollutant. The results showed that under aerated conditions removal ratios
      higher than 91% were achieved, whereas for non-aerated conditions the removal
      ratios were between 50% and 80%, except for 4-NP which achieved removal ratios
      close to 100%. Besides, mass balance showed that the degradation processes were
      more important than the sorption processes. 

PMID- 24096282
TI  - Monomeric carbohydrates production from olive tree pruning biomass: modeling of
      dilute acid hydrolysis.
AB  - Statistical modeling and optimization of dilute sulfuric acid hydrolysis of olive
      tree pruning biomass has been performed using response surface methodology.
      Central composite rotatable design was applied to assess the effect of acid
      concentration, reaction time and temperature on efficiency and selectivity of
      hemicellulosic monomeric carbohydrates to d-xylose. Second-order polynomial model
      was fitted to experimental data to find the optimum reaction conditions by
      multiple regression analysis. The monomeric d-xylose recovery 85% (as predicted
      by the model) was achieved under optimized hydrolysis conditions (1.27% acid
      concentration, 96.5 degrees C and 138 min), confirming the high validity of the
      developed model. The content of d-glucose (8.3%) and monosaccharide degradation
      products (0.1% furfural and 0.04% 5-hydroxymethylfurfural) provided a high
      quality subtract, ready for subsequent biochemical conversion to value-added
      products.

PMID- 24096283
TI  - Bacillus sp. strain P38: an efficient producer of L-lactate from cellulosic
      hydrolysate, with high tolerance for 2-furfural.
AB  - In this study, efficient polymer-grade L-lactic acid production was achieved with
      the strain Bacillus sp. P38 by using cellulosic hydrolysate as the sole carbon
      source. In fed-batch fermentation, 180 g L(-1)L-lactic acid was obtained with a
      volumetric productivity of 2.4 g L(-1)h(-1) and a yield of 0.96 g g(-1) total
      reducing sugars. No D-isomer of lactic acid was detected in the broth. Strain P38
      tolerated up to 10 g L(-1) 2-furfural, and lactate production was sharply
      inhibited only when the 2-furfural concentration was higher than 6 g L(-1).
      Moreover, strain P38 also tolerated high concentrations (>6 g L(-1)) of other
      fermentation inhibitors in cellulosic hydrolysate, such as vanillin and acetic
      acid, although it was slightly sensitive to formic acid. The efficient L-lactic
      acid production, combined with high inhibitor tolerance and efficient pentose
      utilization, indicate that Bacillus sp. P38 is a promising producer of polymer
      grade L-lactic acid from cellulosic biomass.

PMID- 24096284
TI  - Comparative performance of mesophilic and thermophilic anaerobic digestion for
      high-solid sewage sludge.
AB  - In local cities, many small sewage and waste treatment facilities are operated
      independently. To encourage processing by anaerobic digestion at a centralized
      sewage treatment plant (STP), high-solid sewage sludge is helpful because it
      reduces the energy and cost required for transporting the sludge from other STPs.
      Mesophilic and thermophilic anaerobic digestion of sewage sludge at total solids
      concentrations (TS) of 7.5% and 10% were evaluated using laboratory-scale
      continuous reactors. Under the mesophilic condition, sewage sludge of 10% TS was
      successfully treated. Under the thermophilic condition, sewage sludge of 7.5% TS
      was not successfully treated when the total ammonia concentration was over 2000
      mg N/L. Batch experiments showed that it takes a few weeks for the methane
      fermentation activity to recover after being inhibited. The effectiveness of
      adding easily biodegradable organic matter was confirmed. These results show that
      high-solid sewage sludge is suitable for small facilities by controlling the
      operating conditions.

PMID- 24096285
TI  - Carborane enhanced two-photon absorption of tribranched fluorophores for
      fluorescence microscopy imaging.
AB  - Carborane-incorporated (at both carbon and boron sites) tribranched fluorophores
      were efficiently prepared. significantly improves the fluorescence quantum yield.
      exhibits the largest two-photon absorption among the known carborane-based
      derivatives and has been successfully applied in two-photon fluorescence 2D & 3D
      bioimaging. 

PMID- 24096286
TI  - Effects of advanced selection methods on sperm quality and ART outcome.
AB  - In assisted reproductive technology (ART), the role of spermatozoa has evolved
      over the years. In the past, early methods of selecting sperm for ART only
      focused on selecting motile and morphologically normal appearing sperm. It has
      become evident that these methods are inefficient in identifying the most
      suitable sperm for fertilization. Novel methods have thus been created to
      identify highly motile, morphologically normal, viable non-apoptotic spermatozoa
      with intact membranes and high DNA integrity for use in ART. These advanced
      methods of selection utilize our knowledge of unique characteristics of sperm,
      such as sperm surface charge, the presence of hyaluronic acid binding sites on
      sperm, sperm ultramorphology, markers of apoptosis and zona pellucida binding on
      sperm. These methods have shown potential promise in improving ART outcomes.
      Future developments may include Raman spectroscopy, confocal light absorption and
      scattering spectroscopic microscopy, and polarization microscopy. While these
      novel techniques have potential, they come with a cost burden and further studies
      are required to demonstrate their impact on ART outcomes. Furthermore, clinicians
      and human reproductive scientists need to continue to gather knowledge about
      human fertilization and determine the most physiological methods of sperm
      selection. 

PMID- 24096287
TI  - Androgen supplementation in IVF.
AB  - The desired objective of controlled ovarian stimulation (COS) is to allow the
      growth of a cohort of follicles and to facilitate the recovery of a large number
      of fertilizable oocytes. However, poor responders with diminished ovarian reserve
      often fail to respond adequately despite the maximal dose of gonadotropins
      administered, with the results that the number as well as quality of oocytes
      harvested may be very low, thereby decreasing the pregnancy rate in IVF cycles.
      Therefore, successful COS for poor responders remains to be a major challenge in
      IVF program. One of promising strategies for augmenting follicular recruitment in
      poor responders is androgen supplementation. However, there are limited data on
      androgen treatment for poor responders undergoing IVF. Therefore, well-designed
      larger studies with standardized methods are required. 

PMID- 24096288
TI  - Assisted reproductive technologies and uterine factors influencing their success.
AB  - Congenital and acquired uterine factors are known to influence the success of
      assisted reproductive technologies (ARTs). Several studies analyzed the role of
      uterine septa, adenomyosis, myomas, endometrial polyps and intrauterine adhesions
      in female infertility. All of them might cause defective endometrial receptivity
      and consequently decreased embryo implantation and pregnancy rate. In particular,
      septate uterus represents the most frequent Mullerian anomaly leading to an
      increased risk of abortion. Many studies evaluated the role of hysteroscopic
      metroplasty on fertility outcomes, but this topic remains controversial. The role
      of adenomyosis in infertility is still debated and, even if different mechanisms
      have been described to explain implantation failure, there are still conflicting
      findings on the impact of adenomyosis on ART. The effects of myomas on fertility
      mainly depend on their type, so that submucous have a detrimental impact on
      fertility, subserous seem to have no effect, while there is no clear consensus
      regarding the effect of intramural. Consequently, the potential influence of
      myomectomy on fertility outcomes depends on the type, being mandatory only the
      hysteroscopic treatment of submucous myomas. The effect of endometrial polyps on
      endometrial receptivity and fertility is not clear, even if some studies
      identified improvement in pregnancy rates after hysteroscopic polipectomy. In
      presence of intrauterine adhesions, infertility represents the most common
      manifestation and the restoring of normal uterine cavity should be always pursued
      when possible.

PMID- 24096289
TI  - [Phenomenon of induced abortion carried out by adolescents in Europe and Italy
      between 1980 and 2010].
AB  - AIM: We have performed an examination of databases and websites of statistical
      documentation available on the Internet to identify sources of information
      related to the phenomenon of induced abortion carried out by adolescents, to its
      trend over time and in different geographical areas, in order to verify changes
      versus analogies. METHODS: The study was a collection of statistical data,
      describing the trend of induced abortions carried by teenagers, published by the
      open access resources on the Internet. The phenomenon was observed on two
      different units of analysis, women under the age of 20 versus 18 years, placed in
      space-time dimensions consisted of geographical areas of different sizes, Europe,
      Italy, Northern Italy, and Lombardy on the period 1980-2010. Sources showing
      information on the collection and processing of disseminated data were preferred.
      RESULTS: During the examined period the data show the increase of voluntary
      terminations of pregnancy among adolescents in several European countries. In
      Northern Italy and Lombardy abortion rates were higher than in the national area.
      Changes in the characteristics presented by the samples emerged, consisting in
      the decrease of women in their late teens versus the increase of those in mean
      adolescence and the growth of women with foreign citizenship. CONCLUSION: The use
      of statistical resources through the Internet has offered information to assist
      in identification of target populations on which to address intervention
      strategies for prevention. Useful to services in the choice of actions to combat
      the phenomenon of abortion and for the development of the skills required to
      teenagers from current demographic trends. In particular from abasement of age of
      first sexual intercourse, postponement of marriage and of first child to always
      higher age, the increase in migration flows.

PMID- 24096290
TI  - Gastroesophageal reflux in pregnancy: a systematic review on the benefit of raft
      forming agents.
AB  - The prevalence of gastroesophageal reflux disease (GERD) symptoms in pregnancy is
      very high, up to 80%, with a maximum peak during the third trimester. Together
      with lifestyle modifications, antacids and antisecretive agents, such as proton
      pump inhibitors (PPIs) and histamine H2 receptor antagonists (H2RAs), are
      commonly prescribed in non-pregnant, adult population. In certain Countries these
      drugs are not allowed in or are allowed only during the late stages of pregnancy.
      Alginate-based formulations have been used for the symptomatic treatment of
      heartburn for decades, as they usually contain sodium or potassium bicarbonate.
      In the presence of gastric acid, a foamy raft is created above the gastric
      contents. The alginate raft moves into the esophagus in place or ahead of acidic
      gastric contents during reflux episodes physically preventing reflux of gastric
      contents into the esophagus. Alginate-based formulations are allowed with no
      restrictions also in pregnancy: their safety profile make them a very valid
      option taking into account the risk/benefit ratio for both parturient and unborn
      baby. This systematic review paper aims to explore the use of medications for
      treating GERD in pregnancy, including alginate raft-forming-agents, highlighting
      the benefits for both the mother and the fetus. Electronic search in databases
      was conducted on databases such as Medline, PubMed, Ovid retrieving data
      concerning the reflux treatments in pregnancy, with a special focus on alginate
      raft forming antireflux agents. From the literature on alginate use in pregnancy,
      no particular risks have been shown to date for both parturient and unborn baby
      when alginate had been administered during all the pregnancy trimesters. The
      physical mode of action ensures the maximum esophageal protection by the neutral
      foam floating in the stomach, maintaining physiological pH values at stomach
      level, without interfering with the digestive processes. The symptoms' healing
      has been markedly improved during the weeks of observation; the symptoms
      monitored in all studies were: heartburn, regurgitation, pain (chest). After four
      weeks of treatment little or no change was observed in maternal mean sodium or
      potassium concentrations. No sodium restriction diet has been adopted. No edema
      of lower limbs or weight gain occurred. No adverse reactions related to the
      testing drug had been reported and all the authors concluded that alginate was
      safe for the unborn baby. Nowadays pharmacological treatments for GER are
      available as OTC drugs, including antacids, antisecretive agents, PPIs and H2RAs,
      and as medical devices, such as alginate raft forming antireflux agents (i.e.:
      ReflublocTM, Novartis NCH Italy). On this last product, considering the specific
      indication in pregnancy and the safety profile, without restrictions of
      administration during the whole pregnancy period, furthermore the physical mode
      of action, it gives the gynecologists a very important option in treating GER in
      pregnancy, taking care of both pregnant and fetus. Raft-forming-antireflux agents
      are safe and effective in GER treatment during pregnancy.

PMID- 24096291
TI  - Sonographic evaluation of the lower uterine segment thickness in women with a
      single previous Cesarean section.
AB  - AIM: The aim of this paper was to evaluate the lower uterine segment (LUS)
      thickness through transvaginal sonography in late preterm and full term
      pregnancies with a single previous Cesarean section, to correlate the obtained
      LUS measurements with intraoperative observations, and to identify a predictive
      cut-off value in order to select the best candidates for a vaginal birth after
      Cesarean delivery (VBAC). METHODS: Two hundred and fourteen women with a single
      previous Cesarean section who had an ultrasound measurement of the LUS thickness
      (stratified in S1, S2 and S3) in pregnancy were enrolled. The outcome of interest
      was the visual finding of a thin uterine scar at the time of the iterative
      Cesarean section. Linear regression was used to correlate the LUS thickness with
      gestational age (GA). A ROC curve has been used to determine the detection rate
      (DR) and the risk of each actual value of LUS thickness versus a thin uterine
      scar (outcome of interest). RESULTS: The LUS thickness was correlated with the
      gestational age (R2=0.034, P-value =0.005). The DR as estimated by ROC curves to
      detect a translucent lower uterine segment (S3) was 94.1% at a false positive
      rate (FPR) of 20%. The correspondent cut-off value was 1.8 mm. Finally a
      likelihood ratio (LR) of observing S3 was estimated. At the quoted cut-off of 1.8
      mm the LR was 3. As demonstrated, for a segment of 1 mm the LR was instead about
      13. CONCLUSION: The obtained values lead us to the conclusion that a thickness
      less than 1.8 mm can be reasonably considered a valid cut-off value to identify
      patients with a higher risk of thin uterine scar.

PMID- 24096292
TI  - All-cause infant mortality and the risk for subsequent preterm birth.
AB  - AIM: The aim of this paper was to assess the association between all-cause infant
      mortality (death<365 days) in the first pregnancy and the risk of preterm birth
      (<37 weeks of gestation) in the second pregnancy. METHODS: Using the Missouri
      maternally linked dataset from 1989 to 2005 (N.=639134 singleton live births), we
      conducted a population-based retrospective cohort analysis with women who had two
      singleton births between 1989 and 2005. We employed Cox Proportional Hazards
      Regression to generate adjusted hazard ratios (AHR) and 95% confidence intervals
      (CI) to approximate relative risks. RESULTS: Prior infant mortality was
      associated with an increased risk for preterm birth in the second pregnancy
      (AHR=1.96, 95% CI=1.80-2.13). For black women, the risk of preterm birth
      following infant mortality was more than three-fold (AHR=3.37, 95% CI=2.92-3.89),
      while the risk for white women was twice as high (AHR=2.04, 95% CI=1.86-2.26)
      (referent=white women without infant death in the first pregnancy). CONCLUSION:
      Women with a history of infant mortality are at risk for preterm birth in
      subsequent pregnancies. This risk was significantly elevated for black women.
      These findings provide further evidence that previous childbearing experiences
      play a critical role in the occurrence of adverse feto-infant outcomes.

PMID- 24096293
TI  - Vaginal delivery rate in post-term pregnancies with one versus more than one
      dinoprostone gel administrations: an observational study.
AB  - AIM: The study aims to calculate the probability of a successful vaginal delivery
      in post-term low-risk women by using a set of predictors (maternal, fetal, and
      ultrasonographic) according to the number of dinoprostone gel applications.
      METHODS: This was an observational study of a cohort of 174 low-risk post-term
      singleton pregnancies. Parity, cervical status and length, and amniotic fluid
      volume (AFI) were evaluated immediately before prostaglandin gel induction at the
      Department of Obstetrics and Gynecology, University of Bologna, Bologna, Italy
      between January 2010 and October 2011. RESULTS: A consistent difference in
      vaginal delivery rates was observed for women who had one gel administration
      (Group 1) versus those who received either two or three gel administrations
      (Group 2): 77.5% at 24 hours and 97.4% at 48 hours vs. 27% at 24 hours and 54% at
      48 hours (P <0.001 for both the comparisons) respectively. The predictors of a
      vaginal delivery were cervix dilatation and short cervix for Group 1, lower AFI
      for Group 2, and parity for both groups. CONCLUSION: Women who require more than
      one gel administration have a lower rate of vaginal delivery at 24 and 48 hours.
      Maternal, fetal, and ultrasonographic parameters can predict a successful vaginal
      delivery.

PMID- 24096294
TI  - A new surveillance gynecological network to assess the incidence and prevalence
      of genital warts in the Italian female population: lessons learned.
AB  - Human papillomavirus (HPV) is the etiologic agent of genital warts. Genital warts
      are transmitted through sexual contacts and caused in about 90% of the cases by
      HPV types 6 and 11. Worldwide, several million cases of genital warts occur each
      year both in females and males. In Italy, genital warts are not subject to
      mandatory notification; the only available data come from the sentinel
      surveillance system for sexually transmitted infections (STI), which show that
      external genital warts represent the most frequent STI in Italy. However, these
      data are not suitable for estimates of incidence and prevalence of single STI in
      the general population. To obtain more reliable data on the epidemiology of
      genital warts in the female population at large, we implemented a network of
      local gynecologists reporting essential data on all women visited throughout one
      year and detailed data on women who were diagnosed with genital warts. In order
      to organize and create this network, a partnership between the Italian National
      Institute of Health and the Italian Society of Gynecology and Obstetrics was
      constituted to implement the start-up and management of this pilot and unique
      project in Europe. The present paper intends to present the methods used to build
      and implement this surveillance network of local gynecologists. 

PMID- 24096295
TI  - Acetylcholine elevation relieves cognitive rigidity and social deficiency in a
      mouse model of autism.
AB  - Autism spectrum disorders (ASD) are defined by behavioral deficits in social
      interaction and communication, repetitive stereotyped behaviors, and restricted
      interests/cognitive rigidity. Recent studies in humans and animal-models suggest
      that dysfunction of the cholinergic system may underlie autism-related behavioral
      symptoms. Here we tested the hypothesis that augmentation of acetylcholine (ACh)
      in the synaptic cleft by inhibiting acetylcholinesterase may ameliorate autistic
      phenotypes. We first administered the acetylcholinesterase inhibitor (AChEI)
      Donepezil systemically by intraperitoneal (i.p.) injections. Second, the drug was
      injected directly into the rodent homolog of the caudate nucleus, the dorsomedial
      striatum (DMS), of the inbred mouse strain BTBR T+tf/J (BTBR), a commonly-used
      model presenting all core autism-related phenotypes and expressing low brain ACh
      levels. We found that i.p. injection of AChEI to BTBR mice significantly relieved
      autism-relevant phenotypes, including decreasing cognitive rigidity, improving
      social preference, and enhancing social interaction, in a dose-dependent manner.
      Microinjection of the drug directly into the DMS, but not into the ventromedial
      striatum, led to significant amelioration of the cognitive-rigidity and social
      deficiency phenotypes. Taken together, these findings provide evidence of the key
      role of the cholinergic system and the DMS in the etiology of ASD, and suggest
      that elevated cognitive flexibility may result in enhanced social attention. The
      potential therapeutic effect of AChEIs in ASD patients is discussed. 

PMID- 24096296
TI  - Prenatal tobacco exposure and brain morphology: a prospective study in young
      children.
AB  - It is well known that smoking during pregnancy can affect offspring health.
      Prenatal tobacco exposure has been associated with negative behavioral and
      cognitive outcomes in childhood, adolescence, and young adulthood. These
      associations between prenatal tobacco exposure and psychopathology in offspring
      could possibly be explained by the influence of prenatal tobacco exposure on
      brain development. In this prospective study, we investigated the association
      between prenatal tobacco exposure, behavioral and emotional functioning and brain
      morphology in young children. On the basis of age and gender, we matched 113
      children prenatally exposed to tobacco with 113 unexposed controls. These
      children were part of a population-based study in the Netherlands, the Generation
      R Study, and were followed from pregnancy onward. Behavioral and emotional
      functioning was assessed at age 6 with the Child Behavior Checklist. We assessed
      brain morphology using magnetic resonance imaging techniques in children aged 6-8
      years. Children exposed to tobacco throughout pregnancy have smaller total brain
      volumes and smaller cortical gray matter volumes. Continued prenatal tobacco
      exposure was associated with cortical thinning, primarily in the superior
      frontal, superior parietal, and precentral cortices. These children also
      demonstrated increased scores of affective problems. In addition, thickness of
      the precentral and superior frontal cortices was associated with affective
      problems. Importantly, brain development in offspring of mothers who quit smoking
      during pregnancy resembled that of nonexposed controls (no smaller brain volumes
      and no thinning of the cortex). Our findings suggest an association between
      continued prenatal tobacco exposure and brain structure and function in school
      aged children. 

PMID- 24096297
TI  - Towards the 13-valent pneumococcal conjugate universal vaccination: effectiveness
      in the transition era between PCV7 and PCV13 in Italy, 2010-2013.
AB  - Pneumococcal disease epidemiology has changed after introduction of pneumococcal
      conjugate vaccines. Seven-valent vaccine (PCV7) has been effective in reducing
      invasive pneumococcal disease (IPD). In Europe, PCV13 effectiveness was estimated
      at 78% (95% CI: -18-96%) for 2-priming doses. In Italy, PCV7 was introduced in
      2006 in the childhood immunization schedule and replaced with PCV13 in 2010. In
      Apulia, vaccination coverage has reached 95.1% (birth-cohort 2010). We estimated
      PCV program effectiveness and its impact on S. pneumoniae diseases. PCV
      EFFECTIVENESS: We used the screening method. We calculated the Proportion of
      Population Vaccinated from immunization registries and detected cases through a
      laboratory-confirmed surveillance among hospitalized children<=60 months. A
      confirmed IPD case was a child with PCR positive for S. pneumoniae. Differences
      among children were assessed with the Chi-square or the Fisher exact test (P
      value<0.05). PCV IMPACT: We constructed time series using outcome-specific
      Poisson regression models: hospitalization rate in pre-PCV era and
      hospitalization risk ratios (RRs) with 95% CIs for both PCV7 and PCV7/PCV13
      shifting era. We calculated hospitalization RR with 95% CIs comparing pre-PCV
      years with vaccination period. The PCV effectiveness was 84.3% (95% CI: 84.0
      84.6%). In May 2010-January 2013, we enrolled 159 suspected IPD of whom 4 were
      confirmed. Two (fully vaccinated) were caused by serotype 9V, 1 (not vaccinated)
      by serotype 3, 1 (vaccinated with 2 PCV13 doses) by 15B/C. The most important
      reduction was for pneumococcal pneumonia (RR: 0.43, 95% CI: 0.21-0.90). The PCV
      program show promising results in terms of both PCV13 effectiveness and its
      impact in reducing IPD in children<5 years.

PMID- 24096299
TI  - High-resolution optoacoustic mesoscopy with a 24 MHz multidetector translate
      rotate scanner.
AB  - Optoacoustic (photoacoustic) mesoscopy aims at high-resolution optical imaging of
      anatomical, functional, and cellular parameters at depths that go well beyond
      those of optical-resolution optical or optoacoustic microscopy i.e., reaching
      several millimeters in depth. The approach utilizes tomography to achieve
      ultrasonic-diffraction resolution and operates at high-ultrasound frequencies (20
      to 200 MHz) induced by few-nanosecond laser pulse excitation of tissues. We
      investigated here the performance of optoacoustic mesoscopy implemented at 24 MHz
      center frequency and its ability to resolve optical absorption contrast in the
      mouse kidney ex vivo. The developed system achieved better than 30 MUm in-plane
      resolution and 110 MUm elevation resolution over a cylindrical volume of 9-mm
      diameter and 9-mm height. This unprecedented combination of resolution and depth
      was achieved by implementing a translate-rotate detection geometry and by
      tomographic reconstruction. The approach yielded images of optically absorbing
      structures with a level of detail never-before visualized in an intact mouse
      kidney and allows insights into their unperturbed architecture. We discuss the
      ability to offer multispectral acquisitions and enable in vivo imaging.

PMID- 24096300
TI  - Sponges carrying self-microemulsifying drug delivery systems.
AB  - Self-microemulsifying drug delivery systems (SMEDDS) increase the solubility of
      lipophilic drugs. One barrier to their wide application is their liquid nature.
      We report on a new method to solidify SMEDDS-their incorporation in sponges made
      from a hydrophilic natural polymer. Using different freeze-drying schemes,
      sponges were prepared from alginate gels containing microemulsions. The sponges'
      structures were studied with scanning electron microscopy and small angle X-ray
      scattering. The oil droplets survived the drying process, and SMEDDS were present
      as 9 nm-sized objects in the dried sponges. The sponges were rehydrated in water,
      and evidence of the presence of SMEDDS in the rehydrated sponges was found. A
      model hydrophobic molecule, Nile red, was soluble in all dry and rehydrated
      sponges. SMEDDS containing Nile red were gradually released from the sponges, at
      a rate that depended on the drying method. The equilibrium water uptake of the
      sponges was also found to be influenced by the drying scheme. The combination of
      SMEDDS and sponges may be a way to overcome the disadvantages of each component
      separately, provide a solid dosage form for SMEDDS that can sustain the release
      of drugs and also enable utilization of hydrophilic sponges for the delivery of
      hydrophobic drugs.

PMID- 24096298
TI  - Noninvasive evaluation of electrical stimulation impacts on muscle hemodynamics
      via integrating diffuse optical spectroscopies with muscle stimulator.
AB  - Technologies currently available for the monitoring of electrical stimulation
      (ES) in promoting blood circulation and tissue oxygenation are limited. This
      study integrated a muscle stimulator with a diffuse correlation spectroscopy
      (DCS) flow-oximeter to noninvasively quantify muscle blood flow and oxygenation
      responses during ES. Ten healthy subjects were tested using the integrated
      system. The muscle stimulator delivered biphasic electrical current to right leg
      quadriceps muscle, and a custom-made DCS flow-oximeter was used for simultaneous
      measurements of muscle blood flow and oxygenation in both legs. To minimize
      motion artifact of muscle fibers during ES, a novel gating algorithm was
      developed for data acquisition at the time when the muscle was relaxed. ES at 2,
      10, and 50 Hz were applied for 20 min on each subject in three days sequentially.
      Results demonstrate that the 20-min ES at all frequencies promoted muscle blood
      flow significantly. However, only the ES at 10 Hz resulted in significant and
      persistent increases in oxy-hemoglobin concentration during and post ES. This
      pilot study supports the application of the integrated system to quantify tissue
      hemodynamic improvements for the optimization of ES treatment in patients
      suffering from diseases caused by poor blood circulation and low tissue
      oxygenation (e.g., pressure ulcer).

PMID- 24096301
TI  - Laser receptive polyelectrolyte thin films doped with biosynthesized silver
      nanoparticles for antibacterial coatings and drug delivery applications.
AB  - We report a simple method to fabricate multifunctional polyelectrolyte thin films
      to load and deliver the therapeutic drugs. The multilayer thin films were
      assembled by the electrostatic adsorption of poly (allylamine hydrochloride)
      (PAH) and dextran sulfate (DS). The silver nanoparticles (Ag NPs) biosynthesized
      from novel Hybanthus enneaspermus leaf extract as the reducing agent were
      successfully incorporated into the film. The biosynthesized Ag NPs showed
      excellent antimicrobial activity against the range of enteropathogens, which
      could be significantly enhanced when used with commercial antibiotics. The
      assembled silver nano composite multilayer films showed rupture and deformation
      when they are exposed to laser. The Ag NPs act as an energy absorption center,
      locally heat up the film and rupture it under laser treatment. The antibacterial
      drug, moxifloxacin hydrochloride (MH) was successfully loaded into the multilayer
      films. The total amount of MH release observed was about 63% which increased to
      85% when subjected to laser light exposure. Thus, the polyelectrolyte thin film
      reported in our study has significant potential in the field of remote activated
      drug delivery, antibacterial coatings and wound dressings. 

PMID- 24096302
TI  - Development of small-molecule inhibitors targeting adipose triglyceride lipase.
AB  - Adipose triglyceride lipase (ATGL) is rate limiting in the mobilization of fatty
      acids from cellular triglyceride stores. This central role in lipolysis marks
      ATGL as an interesting pharmacological target as deregulated fatty acid
      metabolism is closely linked to dyslipidemic and metabolic disorders. Here we
      report on the development and characterization of a small-molecule inhibitor of
      ATGL. Atglistatin is selective for ATGL and reduces fatty acid mobilization in
      vitro and in vivo. 

PMID- 24096303
TI  - An in vitro evolved glmS ribozyme has the wild-type fold but loses coenzyme
      dependence.
AB  - Uniquely among known ribozymes, the glmS ribozyme-riboswitch requires a small
      molecule coenzyme, glucosamine-6-phosphate (GlcN6P). Although consistent with its
      gene-regulatory function, the use of GlcN6P is unexpected because all of the
      other characterized self-cleaving ribozymes use RNA functional groups or divalent
      cations for catalysis. To determine what active site features make this ribozyme
      reliant on GlcN6P and to evaluate whether it might have evolved from a coenzyme
      independent ancestor, we isolated a GlcN6P-independent variant through in vitro
      selection. Three active site mutations suffice to generate a highly reactive RNA
      that adopts the wild-type fold but uses divalent cations for catalysis and is
      insensitive to GlcN6P. Biochemical and crystallographic comparisons of wild-type
      and mutant ribozymes show that a handful of functional groups fine-tune the RNA
      to be either coenzyme or cation dependent. These results indicate that a few
      mutations can confer new biochemical activities on structured RNAs. Thus,
      families of structurally related ribozymes with divergent function may exist. 

PMID- 24096305
TI  - Metal-organic frameworks built from achiral 3-(5-(pyridin-4-yl)-4H-1,2,4-triazol
      3-yl)benzoic acid: syntheses and structures of metal(II) complexes.
AB  - Using a novel flexible achiral ligand, 3-(5-(pyridin-4-yl)-4H-1,2,4-triazol-3
      yl)benzoic acid (HL), four metal(II)-complexes formulated as ZnL2.2H2O (1),
      CdL2(H2O)2.8H2O (2) and ML2(H2O).H2O (M = Co 3 and Ni 4) have been hydrothermally
      synthesized and structurally characterized by single-crystal X-ray diffraction.
      Complexes 1, 3 and 4 all feature a uninodal 2D layer with a 4(4)-sql topology,
      and two such (4,4) nets interpenetrate in a parallel manner. Complex 2 exhibits a
      similar 4(4)-sql topology, but no interpenetration is observed in complex 2.
      Among the four complexes, only complex 1 is a homochiral network, which is
      evidenced by the CD spectrum. In complex 1, packing of the 2D layers generates a
      41 screw axis along the c direction, and two-fold axes along the a and b
      directions, respectively. In complex 2, the Zn(II) center lies about an inversion
      center, giving rise to the centrosymmetric structure of complex 2. In complexes 3
      and 4, packing of the 2D units generates a 21 screw axis along the c direction in
      the two complexes, and an inversion center is found between two neighboring 2
      fold interpenetrated layers. The work indicates that the chirality of the space
      group for the homochiral complex 1 comes from the supramolecular packing of the
      2D layers.

PMID- 24096304
TI  - Inhibition of weak-affinity epitope-IgE interactions prevents mast cell
      degranulation.
AB  - Development of specific inhibitors of allergy has had limited success, in part,
      owing to a lack of experimental models that reflect the complexity of allergen
      IgE interactions. We designed a heterotetravalent allergen (HtTA) system, which
      reflects epitope heterogeneity, polyclonal response and number of immunodominant
      epitopes observed in natural allergens, thereby providing a physiologically
      relevant experimental model to study mast cell degranulation. The HtTA design
      revealed the importance of weak-affinity epitopes in allergy, particularly when
      presented with high-affinity epitopes. The effect of selective inhibition of weak
      affinity epitope-IgE interactions was investigated with heterobivalent inhibitors
      (HBIs) designed to simultaneously target the antigen- and nucleotide-binding
      sites on the IgE Fab. HBI demonstrated enhanced avidity for the target IgE and
      was a potent inhibitor of degranulation in vitro and in vivo. These results
      demonstrate that partial inhibition of allergen-IgE interactions was sufficient
      to prevent mast cell degranulation, thus establishing the therapeutic potential
      of the HBI design. 

PMID- 24096306
TI  - Construction of the basic skeleton of ophiobolin A and variecolin.
AB  - Ophiobolin and variecolin type sesterterpenoids belong to cyclooctane-containing
      natural products. Both sesterterpenoids have challenging structures and appealing
      biological activities. We envisioned that a key tandem ring closing metathesis of
      dienynes could provide the basic skeleton of ophiobolin A and variecolin. We
      report herein the detailed reactivities of the dienynes which furnished the 5-8-5
      and 5-8-6-5 rings efficiently. 

PMID- 24096307
TI  - Fracture morphology of high shear angle "vertical" femoral neck fractures in
      young adult patients.
AB  - OBJECTIVE: Management of vertical femoral neck fractures in young adults has been
      a challenging clinical problem, resulting in mixed clinical outcomes. A thorough
      understanding of the fracture morphology for this injury pattern is lacking,
      which may contribute to frequent failures of treatment. This study is designed to
      produce a detailed description of the pathoanatomy of these fractures, which may
      ultimately be helpful in developing more informed reduction and fixation
      strategies. DESIGN: Retrospective study of patient records, plain radiographs,
      and computed tomography scans to determine the morphology the Pauwels III femoral
      neck fractures (coronal angle >50 degrees) in young adults. SETTING: Two level I
      and 1 level II regional trauma centers. PATIENTS: All patients 18-49 years of age
      with a surgically repaired, high-energy high shear angle (>50 degrees) femoral
      neck fracture from January 1, 2007, to December 31, 2010. METHODS: One hundred
      thirty-six adult patients younger than 50 years were identified with a femoral
      neck fracture in the study period, of whom 33 met all study criteria. We
      evaluated plain radiography and computed tomography data including fracture
      orientation, comminution, deformity, characteristics of the inferomedial fracture
      spike, and the associated inferomedial calcar's cortical buttress. RESULTS: The
      vertical (coronal) fracture averaged 60 degrees and axial fracture obliquity
      averaged 24 degrees with relative deficiency of the posterior neck on the head
      neck fragment. Major femoral neck comminution (>1.5 cm in any dimension) was
      identified in 96% of cases, mostly located in the inferior (94%) and posterior
      (82%) quadrants. The apical fracture spike of the head segment was found to be in
      line (within 10 degrees) of the neck-shaft axis on the proximal femur 63% of the
      time. Deformity in external rotation averaged 44 degrees (range, 10-68 degrees)
      and shortening of the femur averaged 1.8 cm (range, 0.9-4.4 cm). CONCLUSIONS:
      This study investigated the fracture morphology of isolated, high shear angle
      femoral neck fractures in young adults, which may ultimately lead to improved
      operative reduction and fixation tactics. Given this injury's characteristic
      findings, including fracture orientation, deformity, and comminution, surgeons
      should be cognizant of this pattern's innate instability and potential for
      treatment failure with typical implant constructs.

PMID- 24096308
TI  - Acetabular fractures in the elderly treated with a primary Burch-Schneider
      reinforcement ring, autologous bone graft, and a total hip arthroplasty: a
      prospective study with a 4-year follow-up.
AB  - OBJECTIVES: To investigate the clinical and radiologic outcomes in elderly
      patients suffering from an acetabular fracture operated with an acute primary
      acetabular reinforcement ring, autologous bone graft, and a total hip
      arthroplasty (THA). DESIGN: Prospective cohort study. SETTING: Tertiary care
      university hospital. PATIENTS: Fifteen elderly patients (7 women) with a mean age
      of 76 years and a displaced acetabular fracture after a low-energy trauma were
      included. The fractures involved the anterior column, but no patients with
      associated both column fractures were included. All the patients were able to
      walk independently before the fracture occurred. INTERVENTION: Primary operation
      with a Burch-Schneider reinforcement ring, autologous bone graft, and a THA. MAIN
      OUTCOME MEASUREMENTS: The patients were reviewed at 4, 12, 24, and 48 months
      after the fracture occurred. The outcome assessments included complications,
      reoperations, activity of daily living function, functional scores (Harris hip
      score and short musculoskeletal function assessment), health-related quality of
      life [EuroQol (EQ-5D) index score], and radiologic evaluation. RESULTS: There
      were no prosthetic dislocations, periprosthetic fractures, deep infections, or
      other adverse events. There were no radiologic signs of loosening of the
      reinforcement ring or the prosthesis components at any of the follow up sessions,
      and the autologous bone graft was well incorporated in all the patients at the
      final follow-up. At 48 months, the mean Harris hip score was 88, the mean short
      musculoskeletal function assessment dysfunction score was 30, the bother score
      was 25, and the mean EQ-5D index score was 0.65. All the patients were able to
      walk independently at the final follow-up. CONCLUSIONS: Treatment of displaced
      anterior column, anterior column posterior hemitransverse and transverse
      acetabular fractures in elderly patients using a primary reinforcement ring,
      autologous bone graft, and a THA seems to be a safe option with good functional
      and radiologic outcomes. LEVEL OF EVIDENCE: Therapeutic Level IV. See
      Instructions for Authors for a complete description of levels of evidence.

PMID- 24096309
TI  - Complications associated with retained implants after plate fixation of the
      pediatric forearm.
AB  - OBJECTIVE: Our present study examines the complications of pediatric patients
      treated with plate fixation for forearm fractures. DESIGN: Case series of
      pediatric patients after their forearm fracture was fixed using a plate, with the
      majority of patients retaining their implants. SETTING: Level 1 Trauma Center.
      METHODS: From 1999 to 2009, 58 patients between the ages of 6 and 15 years had
      fixation of their forearm fracture with plates. Thirty-three of these patients
      were available for a long-term follow-up with an average of 6.4 years. The
      patients were interviewed over the phone, and a physician filled out a
      questionnaire with regard to their clinical course. Records and x-ray data were
      reviewed for each patient. Factors such as implant complications, functional
      activity level, pain score, and clinical symptoms were studied. RESULTS:
      Fractures occurred in 7.1% (2/28) of the patients who chose to retain their
      implants. Of the 28 patients who initially chose to leave the implants in place,
      17.9% (5/28) had a partial or complete removal of the implants because of
      irritation. These patients reported the following symptoms: mild pain 42.3%
      (11/26), clicking 34.6% (9/26), ability to feel the plates 73.1% (19/26), and
      mild weakness 26.9% (7/26). The number of patients who reported return to the
      preinjury level of activity was 88.5% (23/26), and 96.2% (25/26) reported being
      satisfied with their clinical outcome when implants were retained. Females had a
      significantly greater subjective weakness of 60.0% (6/10) compared with that of
      males, which was 14.3% (3/21; P = 0.009) after a forearm fracture. The inability
      to return to the preinjury level of activity was significantly greater for
      females, which was 30.0% (3/10) versus 0.0% (0/21) for males (P = 0.008).
      CONCLUSIONS: We concluded that retaining the plates in pediatric forearm
      fractures does not increase the refracture rate compared with the removal from
      the historical rates in the literature. Patients should be warned of possible
      symptoms and complications that may be present with retained plates. Also, a more
      aggressive physical therapy may be considered for females because they were
      observed to have more subjective weakness and dysfunction at long-term follow-up.
      LEVEL OF EVIDENCE: Therapeutic Level IV. See Instructions for Authors for a
      complete description of levels of evidence.

PMID- 24096310
TI  - Treatment of Gartland type III pediatric supracondylar humerus fractures with the
      Kapandji technique in the prone position.
AB  - OBJECTIVE: The purpose of this study was to report the efficacy of the Kapandji
      technique performed in the prone position for humeral supracondylar fractures in
      children. DESIGN: Retrospective. SETTING: Level I trauma center.
      PATIENTS/PARTICIPANTS: We retrospectively reviewed 34 children with Gartland type
      III supracondylar humerus fractures. There were 22 boys and 12 girls with a mean
      age of 5.2 years (range, 1-12.7 years). INTERVENTION: Closed reduction and the
      Kapandji technique were performed in the prone position for all patients. The
      mean follow-up was 17.4 months (range, 13.2-24.8 months). MAIN OUTCOME
      MEASUREMENTS: We assessed preoperative and postoperative radiographs to evaluate
      the quality of the reduction. The clinical outcome was assessed according to the
      criteria of Flynn. RESULTS: All operations were performed in a closed manner, no
      cases required open reduction. Loss of reduction after K-wire fixation was
      identified in 2 patients. There were no pin-related nerve injuries. The mean
      range of elbow motion was 139.6 degrees. The clinical outcome was excellent in 31
      patients, good in 2 patients (97% excellent or good), and fair in 1 patient.
      CONCLUSIONS: This technique is an effective and safe option to treat type III
      supracondylar humerus fractures in children. In patients with severe soft tissue
      swelling, unstable fracture reduction, or unable to achieve acceptable reduction,
      this technique could facilitate fracture reduction and avoid unnecessary open
      reduction. The disadvantage of this technique is that the prone position is less
      desirable for airway management. LEVEL OF EVIDENCE: Therapeutic Level IV. See
      Instructions for Authors for a complete description of levels of evidence.

PMID- 24096311
TI  - Repair effects of exogenous SOD on Bacillus subtilis against gamma radiation
      exposure.
AB  - Superoxide dismutase (SOD) is an enzyme that removes free radicals from cells in
      many organisms. In order to further characterize these repair effects and their
      mechanism when subjected to radiation, Bacillus subtilis cells were exposed to
      gamma radiation and the cell survival rate, intracellular SOD activity, and DNA
      double-strand breakage were investigated. Vegetative cells of B. subtilis were
      irradiated by (60)Co gamma radiation at varying doses and subsequently exposed to
      varying levels of exogenous SOD. Standard plate-count, xanthine oxidase, and
      pulsed-field gel electrophoresis (PFGE) methods were employed to investigate the
      repair effects. The results showed that the exogenous SOD could significantly
      improve cell survival rate and intracellular SOD activity after gamma radiation.
      The cell survival rate was elevated 30-87 times above levels observed in control
      samples. Adding exogenous SOD into gamma irradiated cells may dramatically
      increase intracellular SOD activity (p < 0.01), while percentage of DNA release
      (PR) values may decrease significantly when cells are treated with SOD. The
      repair effects were observed to vary with the gamma radiation dose and SOD
      concentration. These findings suggest that exogenous SOD may have the ability to
      repair vegetative B. subtilis cell damage after irradiated by gamma radiation.
      DNA strand scission may also be prevented by addition of SOD. This research
      contributes to better understanding of protection from the effects of free
      radicals and their mechanisms, an ongoing process in many organisms that involves
      the cellular response to gamma radiation, which occurs naturally in soil and
      water, as well as in unusual cases of high-dosage exposure.

PMID- 24096312
TI  - Academic abilities in children and adolescents with a history of autism spectrum
      disorders who have achieved optimal outcomes.
AB  - This study examines the academic abilities of children and adolescents who were
      once diagnosed with an autism spectrum disorder, but who no longer meet
      diagnostic criteria for this disorder. These individuals have achieved social and
      language skills within the average range for their ages, receive little or no
      school support, and are referred to as having achieved "optimal outcomes."
      Performance of 32 individuals who achieved optimal outcomes, 41 high-functioning
      individuals with a current autism spectrum disorder diagnosis (high-functioning
      autism), and 34 typically developing peers was compared on measures of decoding,
      reading comprehension, mathematical problem solving, and written expression.
      Groups were matched on age, sex, and nonverbal IQ; however, the high-functioning
      autism group scored significantly lower than the optimal outcome and typically
      developing groups on verbal IQ. All three groups performed in the average range
      on all subtests measured, and no significant differences were found in
      performance of the optimal outcome and typically developing groups. The high
      functioning autism group scored significantly lower on subtests of reading
      comprehension and mathematical problem solving than the optimal outcome group.
      These findings suggest that the academic abilities of individuals who achieved
      optimal outcomes are similar to those of their typically developing peers, even
      in areas where individuals who have retained their autism spectrum disorder
      diagnoses exhibit some ongoing difficulty. 

PMID- 24096313
TI  - Abstracts of the ESICM 26th Annual Congress, 5-9 October, 2013, Paris, France.

PMID- 24096315
TI  - Influence of auditory and audiovisual stimuli on the right-left prevalence
      effect.
AB  - When auditory stimuli are used in two-dimensional spatial compatibility tasks,
      where the stimulus and response configurations vary along the horizontal and
      vertical dimensions simultaneously, a right-left prevalence effect occurs in
      which horizontal compatibility dominates over vertical compatibility. The right
      left prevalence effects obtained with auditory stimuli are typically larger than
      that obtained with visual stimuli even though less attention should be demanded
      from the horizontal dimension in auditory processing. In the present study, we
      examined whether auditory or visual dominance occurs when the two-dimensional
      stimuli are audiovisual, as well as whether there will be cross-modal
      facilitation of response selection for the horizontal and vertical dimensions. We
      also examined whether there is an additional benefit of adding a pitch dimension
      to the auditory stimulus to facilitate vertical coding through use of the spatial
      musical association of response codes (SMARC) effect, where pitch is coded in
      terms of height in space. In Experiment 1, we found a larger right-left
      prevalence effect for unimodal auditory than visual stimuli. Neutral, non-pitch
      coded, audiovisual stimuli did not result in cross-modal facilitation, but did
      show evidence of visual dominance. The right-left prevalence effect was
      eliminated in the presence of SMARC audiovisual stimuli, but the effect
      influenced horizontal rather than vertical coding. Experiment 2 showed that the
      influence of the pitch dimension was not in terms of influencing response
      selection on a trial-to-trial basis, but in terms of altering the salience of the
      task environment. Taken together, these findings indicate that in the absence of
      salient vertical cues, auditory and audiovisual stimuli tend to be coded along
      the horizontal dimension and vision tends to dominate audition in this two
      dimensional spatial stimulus-response task. 

PMID- 24096316
TI  - High-dimensional analysis of human CD8(+) T cell phenotype, function, and antigen
      specificity.
AB  - Antigen-specific T cells are critical initiators and orchestrators of the
      adaptive immune response. Categorizing antigen-specific T cell subsets is not a
      simple task given the diversity of these cells and the large number of parameters
      that can be considered. Here, we focus on human CD8(+) T cells and discuss the
      utility of high-dimensional mass cytometric analysis techniques for the
      concurrent identification and characterization of antigen-specific T cells
      involved in immunological homeostasis and disease. We first provide an overview
      of previously identified T cell subsets. We then discuss the segregation of
      antigen-specific T cells based on protein expression through surface and/or
      intracellular staining, on functional capacity through measurement expression of
      cytokines or other inducible markers, and on the antigen-specificity of the cell
      assessed using peptide-major histocompatibility complex multimers. High
      dimensional mass cytometry enables a deeper and more integrated view of all three
      aspects of antigen-specific T cell diversity than do traditional techniques. Use
      of mass cytometry for precise measurement of the status of antigen-specific
      immune responses should result in better prediction of vaccine efficacy and
      disease outcomes. 

PMID- 24096317
TI  - Repetitive MR measurements of lung volume in fetuses with congenital
      diaphragmatic hernia: individual development of pulmonary hypoplasia during
      pregnancy and calculation of weekly lung growth rates.
AB  - OBJECTIVE: To investigate individual changes in fetal lung volume (FLV) in
      fetuses with isolated congenital diaphragmatic hernia (CDH) and to calculate
      weekly growth rates of the FLV using serial MR examinations during pregnancy.
      METHODS: MR-FLV was measured in 89 fetuses with CDH. All fetuses received two
      MRIs. A mean weekly growth rate of the FLV was determined for each fetus and
      compared with the growth rate of healthy fetuses. RESULTS: Mean observed-to
      expected MR-FLV (o/e MR-FLV) measured at the first MRI was 33.3 +/- 12.2% and
      29.5 +/- 10.9% at the second MRI. In 61% of all fetuses (54/89) the o/e MR-FLV
      decreased during pregnancy, 26% (23/89) showed an increase in the o/e MR-FLV and
      13 % (12/89) had stable values. First and last o/e MR-FLV values were
      significantly associated with mortality and neonatal extracorporeal membrane
      oxygenation (ECMO) requirement with a higher prognostic accuracy of MR-FLV
      measurements near delivery. Patients with CDH had lower weekly lung growth rates
      than healthy fetuses. There was a significant difference in the mean weekly
      growth rate between survivors and non-survivors and patients with and without
      ECMO requirement. CONCLUSION: Individual development of FLV in patients with CDH
      during pregnancy is extremely variable. Follow-up MR-FLV measurements are
      advisable before deciding upon pre- and postnatal therapeutic options. KEY
      POINTS: * Lung development in congenital diaphragmatic hernia (CDH) during
      pregnancy is extremely variable. * MRI demonstrates that lung growth rate is
      reduced in fetuses with CDH. * The final observed-to-expected fetal lung volume
      provides the best prognostic information. * Follow-up measurements are advisable
      before deciding upon therapeutic options.

PMID- 24096318
TI  - Characterization of the Sandfly fever Naples species complex and description of a
      new Karimabad species complex (genus Phlebovirus, family Bunyaviridae).
AB  - Genomic and antigenic characterization of members of the Sandfly fever Naples
      virus (SFNV) complex reveals the presence of five clades that differ in their
      geographical distribution. Saint Floris and Gordil viruses, both found in Africa,
      form one clade; Punique, Granada and Massilia viruses, all isolated in the
      western Mediterranean, constitute a second; Toscana virus, a third; SFNV isolates
      from Italy, Cyprus, Egypt and India form a fourth; while Tehran virus and a
      Serbian isolate Yu 8/76, represent a fifth. Interestingly, this last clade
      appears not to express the second non-structural protein ORF. Karimabad virus,
      previously classified as a member of the SFNV complex, and Gabek Forest virus are
      distinct and form a new species complex (named Karimabad) in the Phlebovirus
      genus. In contrast with the high reassortment frequency observed in some South
      American phleboviruses, the only virus of the SFNV complex with evidence of
      reassortment was Granada virus. 

PMID- 24096319
TI  - Production of single-round infectious chimeric flaviviruses with DNA-based
      Japanese encephalitis virus replicon.
AB  - A method for rapid production of single-round infectious particles (SRIPs) of
      flavivirus would be useful for viral mutagenesis studies. Here, we established a
      DNA-based production system for SRIPs of flavivirus. We constructed a Japanese
      encephalitis virus (JEV) subgenomic replicon plasmid, which lacked the C-prM-E
      (capsid-pre-membrane-envelope) coding region, under the control of the
      cytomegalovirus promoter. When the JEV replicon plasmid was transiently co
      transfected with a JEV C-prM-E expression plasmid into 293T cells, SRIPs were
      produced, indicating successful trans-complementation with JEV structural
      proteins. Equivalent production levels were observed when C and prM-E proteins
      were provided separately. Furthermore, dengue types 1-4, West Nile, yellow fever
      or tick-borne encephalitis virus prM-E proteins could be utilized for production
      of chimaeric flavivirus SRIPs, although the production was less efficient for
      dengue and yellow fever viruses. These results indicated that our plasmid-based
      system is suitable for investigating the life cycles of flaviviruses, diagnostic
      applications and development of safer vaccine candidates. 

PMID- 24096320
TI  - Enhancement of enteric adenovirus cultivation in a novel Ras-overexpressing cell
      line.
AB  - Enteric human adenoviruses (HAdVs; serotypes 40 and 41) have been identified as
      an emerging cause of drinking water contamination. Due to their fastidious
      characteristics, HAdVs are difficult to cultivate and therefore not detected
      easily by standard mammalian cell cultivation methods. Here we found that human
      embryonic kidney 293 cells, transformed transiently with Ras, enhanced HAdV
      replication by more than threefold. We also constructed a stable cell line
      overexpressing the Ras protein, 293-Ras, in which the replication of three HAdV
      strains of serotypes 40 and 41 was increased markedly. However, only HAdV
      replication was enhanced; infection of 293 and 293-Ras cells with human
      rhinivorus-6 showed no significant differences in replication rate. Infected 293
      Ras cells exhibited an increased level and phosphorylation of extracellular
      regulated kinase (ERK). In addition, the Ras-mediated increase in HAdV
      replication was impaired by the mitogen-activated protein kinase/ERK kinase
      (MEK1) inhibitor U0126, suggesting direct involvement of the MEK1/ERK pathway in
      enhanced HAdV replication. Based on these results, we suggest that the 293-Ras
      cell line be used for the efficient detection and cultivation of HAdV strains in
      both clinical and environmental specimens. 

PMID- 24096321
TI  - Effects of breast and colorectal cancer on labour market outcomes-average effects
      and educational gradients.
AB  - We estimate causal effects of breast and colorectal cancer on labour market
      outcomes 1-3 years after the diagnosis. Based on Danish administrative data we
      estimate average treatment effects on the treated by propensity score weighting
      methods using persons with no cancer diagnosis as control group. We conduct
      robustness checks using matching, difference-in-differences methods and an
      alternative control group of later cancer patients. The different methods give
      approximately the same results. Cancer increases the risks of leaving the labour
      force and receiving disability pension, and the effects are larger for the less
      educated. Effects on income are small and mostly insignificant. We investigate
      some of the mechanisms which may be important in explaining the educational
      gradient in effects of cancer on labour market attachment. 

PMID- 24096323
TI  - Assessment of myocardial matrix expansion with cardiac magnetic resonance:
      entering a new area of cardiac risk stratification in type 2 diabetes mellitus?

PMID- 24096322
TI  - CAR regulates epithelial cell junction stability through control of E-cadherin
      trafficking.
AB  - CAR (Coxsackie and Adenovirus Receptor) is the primary docking receptor for typeB
      coxsackie viruses and subgroup C adenoviruses. CAR is a member of the JAM family
      of adhesion receptors and is located to both tight and adherens junctions between
      epithelial cells where it can assemble adhesive contacts through homodimerisation
      in trans. However, the role of CAR in controlling epithelial junction dynamics
      remains poorly understood. Here we demonstrate that levels of CAR in human
      epithelial cells play a key role in determining epithelial cell adhesion through
      control of E-cadherin stability at cell-cell junctions. Mechanistically, we show
      that CAR is phosphorylated within the C-terminus by PKCdelta and that this in
      turn controls Src-dependent endocytosis of E-cadherin at cell junctions. This
      data demonstrates a novel role for CAR in regulating epithelial homeostasis. 

PMID- 24096324
TI  - Clinical outcomes of patients with low-flow, low-gradient, severe aortic stenosis
      and either preserved or reduced ejection fraction undergoing transcatheter aortic
      valve implantation.
AB  - AIMS: Our aim was to evaluate the invasive haemodynamic indices of high-risk
      symptomatic patients presenting with 'paradoxical' low-flow, low-gradient, severe
      aortic stenosis (AS) (PLF-LG) and low-flow, low-gradient severe AS (LEF-LG) and
      to compare clinical outcomes following transcatheter aortic valve implantation
      (TAVI) among these challenging AS subgroups. METHODS AND RESULTS: Of 534
      symptomatic patients undergoing TAVI, 385 had a full pre-procedural right and
      left heart catheterization. A total of 208 patients had high-gradient severe AS
      [HGAS; mean gradient (MG) >=40 mmHg], 85 had PLF-LG [MG <= 40 mmHg, indexed
      aortic valve area [iAVA] <=0.6 cm(2) m(-2), stroke volume index <=35 mL/m(2),
      ejection fraction (EF) >=50%], and 61 had LEF-LG (MG <= 40 mmHg, iAVA <=0.6 cm(2)
      m(-2), EF <=40%). Compared with HGAS, PLF-LG and LEF-LG had higher systemic
      vascular resistances (HGAS: 1912 +/- 654 vs. PLF-LG: 2006 +/- 586 vs. LEF-LG:
      2216 +/- 765 dyne s m(-5), P = 0.007) but lower valvulo-arterial impedances
      (HGAS: 7.8 +/- 2.7 vs. PLF-LG: 6.9 +/- 1.9 vs. LEF-LG: 7.7 +/- 2.5 mmHg mL(-1) m(
      2), P = 0.027). At 30 days, no differences in cardiac death (6.5 vs. 4.9 vs.
      6.6%, P = 0.90) or death (8.4 vs. 6.1 vs. 6.6%, P = 0.88) were observed among
      HGAS, PLF-LG, and LEF-LG groups, respectively. At 1 year, New York Heart
      Association functional improvement occurred in most surviving patients (HGAS:
      69.2% vs. PLF-LG: 71.7% vs. LEF-LG: 89.3%, P = 0.09) and no significant
      differences in overall mortality were observed (17.6 vs. 20.5 vs. 24.5%, P =
      0.67). Compared with HGAS, LEF-LG had a higher 1 year cardiac mortality (adjusted
      hazard ratio 2.45, 95% confidence interval 1.04-5.75, P = 0.04). CONCLUSION: TAVI
      in PLF-LG or LEF-LG patients is associated with overall mortality rates
      comparable with HGAS patients and all groups profit symptomatically to a similar
      extent.

PMID- 24096326
TI  - TAVI in a low left main coronary artery ostium and wide aortic sinus of Valsava.

PMID- 24096325
TI  - Reperfusion therapy of acute ischaemic stroke and acute myocardial infarction:
      similarities and differences.
AB  - The evolution of reperfusion therapy in acute myocardial infarction and acute
      ischaemic stroke has many similarities: thrombolysis is superior to placebo,
      intra-arterial thrombolysis is not superior to intravenous (i.v.), facilitated
      intervention is of questionable value, and direct mechanical recanalization
      without thrombolysis is proven (myocardial infarction) or promising (stroke) to
      be superior to thrombolysis-but only when started with no or minimal delay.
      However, there are also substantial differences. Direct catheter-based
      thrombectomy in acute ischaemic stroke is more difficult than primary angioplasty
      (in ST-elevation myocardial infarction [STEMI]) in many ways: complex pre
      intervention diagnostic workup, shorter time window for clinically effective
      reperfusion, need for an emergent multidisciplinary approach from the first
      medical contact, vessel tortuosity, vessel fragility, no evidence available about
      dosage and combination of peri-procedural antithrombotic drugs, risk of
      intracranial bleeding, unclear respective roles of thrombolysis and mechanical
      intervention, lower number of suitable patients, and thus longer learning curves
      of the staff. Thus, starting acute stroke interventional programme requires a lot
      of learning, discipline, and humility. Randomized trials comparing different
      reperfusion strategies provided similar results in acute ischaemic stroke as in
      STEMI. Thus, it might be expected that also a future randomized trial comparing
      direct (primary) catheter-based thrombectomy vs. i.v. thrombolysis could show
      superiority of the mechanical intervention if it would be initiated without
      delay. Such randomized trial is needed to define the role of mechanical
      intervention alone in acute stroke treatment.

PMID- 24096327
TI  - Acute myocardial infarction caused by coronary tumour embolism.

PMID- 24096328
TI  - Unruptured sinus valsalva aneurysm in bicuspid aortic valve as an unusual cause
      of seasonal dyspnoea.

PMID- 24096329
TI  - Right atrial and ventricular angiosarcoma.

PMID- 24096330
TI  - Exercise-related out-of-hospital cardiac arrest in the general population:
      incidence and prognosis.
AB  - AIMS: Although regular physical activity has beneficial cardiovascular effects,
      exercise can trigger an acute cardiac event. We aimed to determine the incidence
      and prognosis of exercise-related out-of-hospital cardiac arrest (OHCA) in the
      general population. METHODS AND RESULTS: We prospectively collected all OHCAs in
      persons aged 10-90 years from January 2006 to January 2009 in the Dutch province
      North Holland. The relation between exercise during or within 1 h before OHCA and
      outcome was analysed using multivariable logistic regression, adjusted for age,
      gender, location, bystander witness, bystander cardiopulmonary resuscitation
      (CPR), automated external defibrillator (AED) use, initial rhythm, and Emergency
      Medical System response time. Of 2524 OHCAs, 143 (5.7%) were exercise related (7
      <=35 years, 93% men). Exercise-related OHCA incidence was 2.1 per 100 000 person
      years overall and 0.3 per 100 000 person-years in those <=35 years. Survival
      after exercise-related OHCA was distinctly better than after non-exercise related
      OHCA (46.2 vs. 17.2%) [unadjusted odds ratio (OR) 4.12; 95%CI 2.92-5.82; P <
      0.001], even after adjustment for abovementioned variables (OR 2.63; 95%CI, 1.23
      5.54; P = 0.01). In the 69 victims aged <=35 years, exercise was not associated
      with better survival: 14.3 vs. 17.7% in non-exercise-related OHCA (OR 0.77; 95%CI
      0.08-7.08; P = 0.82). CONCLUSION: Exercise-related OHCA has a low incidence,
      particularly in the young. Cardiac arrests occurring during or shortly after
      exercise carry a markedly better prognosis than non-exercise-related arrests in
      persons >35 years. This study establishes the favourable outcome of exercise
      related OHCA and should have direct implications for public health programs to
      prevent exercise-related sudden death.

PMID- 24096331
TI  - Rare cause of myocardial infarction, stroke, and lung tumour.

PMID- 24096332
TI  - Transcriptional activation of heat shock protein 90 mediated via a proximal
      promoter region as trigger of caspofungin resistance in Aspergillus fumigatus.
AB  - Invasive aspergillosis is a deadly infection for which new antifungal therapies
      are needed. Heat shock protein 90 (Hsp90) is an essential chaperone in
      Aspergillus fumigatus representing an attractive antifungal target. Using a
      thiamine-repressible promoter (pthiA), we showed that genetic repression of Hsp90
      significantly reduced virulence in a murine model of invasive aspergillosis.
      Moreover, substituting the A. fumigatus hsp90 promoter with 2 artificial
      promoters (potef, pthiA) and the Candida albicans hsp90 promoter resulted in
      hypersensitivity to caspofungin and abolition of the paradoxical effect
      (resistance at high caspofungin concentrations). By inducing truncations in the
      hsp90 promoter, we identified a 100-base pair proximal sequence that triggers a
      significant increase of hsp90 expression (>=1.5-fold) and is essential for the
      paradoxical effect. Preventing this increase of hsp90 expression was sufficient
      to abolish the paradoxical effect and therefore optimize the antifungal activity
      of caspofungin. 

PMID- 24096334
TI  - Keeping eosinophils on time--ILC2 it!

PMID- 24096333
TI  - Exacerbation of invasive Candida albicans infection by commensal bacteria or a
      glycolipid through IFN-gamma produced in part by iNKT cells.
AB  - BACKGROUND: The commensal yeast Candida albicans is a major cause of invasive
      fungal infections. Despite treatment with antifungal agents, the mortality rate
      attributed to these types of infection is high. Although numerous cases have been
      reported regarding a poor outcome for patients with bacterial and C. albicans
      coinfection, the mechanisms by which the coinfecting bacteria exacerbate the C.
      albicans infection remain elusive. METHODS AND RESULTS: We evaluated how
      glycolipid-mediated activation of invariant natural killer T (iNKT) cells affects
      the clearance of C. albicans. Surprisingly, C. albicans-infected, glycolipid
      treated mice exhibited significantly lower survival rates, increased fungal
      burden, and higher interleukin (IL)-6 production in the kidneys compared with
      control mice. Glycolipid-induced exacerbation of C. albicans infection was not
      observed in interferon-gamma knockout (IFN-gammaKO) mice. In the C. albicans
      infected, glycolipid-treated mice, the number of neutrophils in the blood and
      bone marrow dramatically decreased in an IFN-gamma-dependent manner. Furthermore,
      mice that were coinfected with C. albicans and nonfermentative gram-negative
      commensal bacteria exhibited increased fungal burden and inflammatory cytokine
      production in the kidneys that were dependent on IFN-gamma and iNKT cells.
      CONCLUSIONS: Our results indicate that coinfecting commensal bacteria exacerbate
      C. albicans infection through IFN-gamma produced, in part, by iNKT cells.

PMID- 24096335
TI  - Two versions of the Ikaros tale.

PMID- 24096336
TI  - SNPing at FOXO3 to limit inflammation.

PMID- 24096338
TI  - A midwifery-led in-hospital birth center within an academic medical center:
      successes and challenges.
AB  - The University of California San Diego Community Women's Health Program (CWHP)
      has emerged as a successful and sustainable coexistence model of women's
      healthcare. The cornerstone of this midwifery practice is California's only in
      hospital birth center. Located within the medical center, this unique and
      physically separate birth center has been the site for more than 4000 births.
      With 10% cesarean delivery and 98% breast-feeding rates, it is an exceptional
      example of low-intervention care. Integrating this previously freestanding birth
      center into an academic center has brought trials of mistrust and ineffectual
      communication. Education, consistent leadership, and development of
      multidisciplinary guidelines aided in overcoming these challenges. This
      collaborative model provides a structure in which residents learn to be
      respectful consultants and appreciate differences in medical practice. The CWHP
      and its Birth Center illustrates that through persistence and flexibility a
      collaborative model of maternity services can flourish and not only positively
      influence new families but also future generations of providers. 

PMID- 24096339
TI  - Visual and near IR (NIR) fluorescence detection of Cr3+ in aqueous media via
      spirobenzopyran ring opening with application in logic gate and bio-imaging.
AB  - A new spirobenzopyran derivative (SPNH) was designed and synthesized which was
      applied in simultaneous colorimetric and NIR fluorescence detections for Cr(3+).
      This spirobenzopyran receptor is normally colorless in aqueous organic media but
      the formation of merocyanine occurs by Cr(3+) showing a yellow color. Here the
      formation of yellow color in UV-vis spectra and strong NIR fluorescence emission
      at 675 nm makes SPNH a good sensor for Cr(3+) ion. It is also found to be useful
      in cell imaging and in construction of logic gate. It shows INHIBIT gate in
      fluorescence and OR gate in absorption. To the best of our knowledge, this is the
      first report of NIR fluorescence emission of a spirobenzopyran derivative by
      Cr(3+) and its application to cell-biology and also in the logic gate.

PMID- 24096337
TI  - Microbiota-mediated colonization resistance against intestinal pathogens.
AB  - Commensal bacteria inhabit mucosal and epidermal surfaces in mice and humans, and
      have effects on metabolic and immune pathways in their hosts. Recent studies
      indicate that the commensal microbiota can be manipulated to prevent and even to
      cure infections that are caused by pathogenic bacteria, particularly pathogens
      that are broadly resistant to antibiotics, such as vancomycin-resistant
      Enterococcus faecium, Gram-negative Enterobacteriaceae and Clostridium difficile.
      In this Review, we discuss how immune- mediated colonization resistance against
      antibiotic-resistant intestinal pathogens is influenced by the composition of the
      commensal microbiota. We also review recent advances characterizing the ability
      of different commensal bacterial families, genera and species to restore
      colonization resistance to intestinal pathogens in antibiotic-treated hosts. 

PMID- 24096341
TI  - Neighboring parenchyma cells contribute to Arabidopsis xylem lignification, while
      lignification of interfascicular fibers is cell autonomous.
AB  - Lignin is a critical structural component of plants, providing vascular integrity
      and mechanical strength. Lignin precursors (monolignols) must be exported to the
      extracellular matrix where random oxidative coupling produces a complex lignin
      polymer. The objectives of this study were twofold: to determine the timing of
      lignification with respect to programmed cell death and to test if nonlignifying
      xylary parenchyma cells can contribute to the lignification of tracheary elements
      and fibers. This study demonstrates that lignin deposition is not exclusively a
      postmortem event, but also occurs prior to programmed cell death. Radiolabeled
      monolignols were not detected in the cytoplasm or vacuoles of tracheary elements
      or neighbors. To experimentally define which cells in lignifying tissues
      contribute to lignification in intact plants, a microRNA against cinnamoyl CoA
      reductase1 driven by the promoter from cellulose synthase7 (ProCESA7:miRNA CCR1)
      was used to silence monolignol biosynthesis specifically in cells developing
      lignified secondary cell walls. When monolignol biosynthesis in ProCESA7:miRNA
      CCR1 lines was silenced in the lignifying cells themselves, but not in the
      neighboring cells, lignin was still deposited in the xylem secondary cell walls.
      Surprisingly, a dramatic reduction in cell wall lignification of extraxylary
      fiber cells demonstrates that extraxylary fibers undergo cell autonomous
      lignification.

PMID- 24096342
TI  - The photosynthesis affected mutant68-like protein evolved from a PSII assembly
      factor to mediate assembly of the chloroplast NAD(P)H dehydrogenase complex in
      Arabidopsis.
AB  - In vascular plants, the chloroplast NAD(P)H dehydrogenase complex (NDH-C) is
      assembled from five distinct subcomplexes, the membrane-spanning (subM) and the
      luminal (subL) subcomplexes, as well as subA, subB, and subE. The assembly
      process itself is poorly understood. Vascular plant genomes code for two related
      intrinsic thylakoid proteins, photosynthesis-affected mutant68 (PAM68), a
      photosystem II assembly factor, and photosynthesis-affected mutant68-like
      (PAM68L). As we show here, inactivation of Arabidopsis thaliana PAM68L in the
      pam68l-1 mutant identifies PAM68L as an NDH-C assembly factor. The mutant lacks
      functional NDH holocomplexes and accumulates three distinct NDH-C assembly
      intermediates (subB, subM, and subA+L), which are also found in mutants defective
      in subB assembly (ndf5) or subM expression (chlororespiratory reduction4-3
      mutant). NDH-C assembly in the cyanobacterium Synechocystis sp PCC 6803 and the
      moss Physcomitrella patens does not require PAM68 proteins, as demonstrated by
      the analysis of knockout lines for the single-copy PAM68 genes in these species.
      We conclude that PAM68L mediates the attachment of subB- and subM-containing
      intermediates to a complex that contains subA and subL. The evolutionary
      appearance of subL and PAM68L during the transition from mosses like P. patens to
      flowering plants suggests that the associated increase in the complexity of the
      NDH-C might have been facilitated by the recruitment of evolutionarily novel
      assembly factors like PAM68L.

PMID- 24096343
TI  - Nighttime sugar starvation orchestrates gibberellin biosynthesis and plant growth
      in Arabidopsis.
AB  - A plant's eventual size depends on the integration of its genetic program with
      environmental cues, which vary on a daily basis. Both efficient carbon metabolism
      and the plant hormone gibberellin are required to guarantee optimal plant growth.
      Yet, little is known about the interplay between carbon metabolism and
      gibberellins that modulates plant growth. Here, we show that sugar starvation in
      Arabidopsis thaliana arising from inefficient starch metabolism at night strongly
      reduces the expression of ent-kaurene synthase, a key regulatory enzyme for
      gibberellin synthesis, the following day. Our results demonstrate that plants
      integrate the efficiency of photosynthesis over a period of days, which is
      transduced into a daily rate of gibberellin biosynthesis. This enables a plant to
      grow to a size that is compatible with its environment. 

PMID- 24096345
TI  - Transition metal-free one-pot cascade synthesis of 7-oxa-2
      azatricyclo[7.4.0.0(2,6)]trideca-1(9),10,12-trien-3-ones from biomass-derived
      levulinic acid under mild conditions.
AB  - An efficient, environmentally benign, transition-metal free, tandem C-N, C-O bond
      formation reaction is developed for the synthesis of tricyclic 7-oxa-2
      azatricyclo[7.4.0.0(2,6)]trideca-1(9),10,12-trien-3-ones and their homologs from
      easily available starting materials, including renewable levulinic acid, a keto
      acid. The reaction of keto acids with methyl chloroformate and variously
      substituted o-aminobenzyl alcohols using triethylamine as a base in toluene at
      room temperature gave good to excellent yields. This newly developed protocol was
      successfully utilized for the synthesis of a variety of polycyclic 7-oxa-2
      azatricyclo[7.4.0.0(2,6)]trideca-1(9),10,12-trien-3-ones and related compounds. 

PMID- 24096344
TI  - A rice cis-natural antisense RNA acts as a translational enhancer for its cognate
      mRNA and contributes to phosphate homeostasis and plant fitness.
AB  - cis-natural antisense transcripts (cis-NATs) are widespread in plants and are
      often associated with downregulation of their associated sense genes. We found
      that a cis-NAT positively regulates the level of a protein critical for phosphate
      homeostasis in rice (Oryza sativa). PHOSPHATE1;2 (PHO1;2), a gene involved in
      phosphate loading into the xylem in rice, and its associated cis-NATPHO1;2 are
      both controlled by promoters active in the vascular cylinder of roots and leaves.
      While the PHO1;2 promoter is unresponsive to the plant phosphate status, the cis
      NATPHO1;2 promoter is strongly upregulated under phosphate deficiency. Expression
      of both cis-NATPHO1;2 and the PHO1;2 protein increased in phosphate-deficient
      plants, while the PHO1;2 mRNA level remained stable. Downregulation of cis
      NATPHO1;2 expression by RNA interference resulted in a decrease in PHO1;2
      protein, impaired the transfer of phosphate from root to shoot, and decreased
      seed yield. Constitutive overexpression of NATPHO1;2 in trans led to a strong
      increase of PHO1;2, even under phosphate-sufficient conditions. Under all
      conditions, no changes occurred in the level of expression, sequence, or nuclear
      export of PHO1;2 mRNA. However, expression of cis-NATPHO1;2 was associated with a
      shift of both PHO1;2 and cis-NATPHO1;2 toward the polysomes. These findings
      reveal an unexpected role for cis-NATPHO1;2 in promoting PHO1;2 translation and
      affecting phosphate homeostasis and plant fitness. 

PMID- 24096346
TI  - Pancreatic mucinous cystic tumor in Turner syndrome: How a tumor bends to a
      genetic disease.
AB  - INTRODUCTION: Mucinous cystic neoplasms (MCN) are uncommon tumors of the
      pancreatic corpus/tail occurring mostly in middle-aged women, with a variable
      clinico-biological behavior. On histology, MCNs concurrently show an epithelial
      mucosecreting component with ovarian-type stromal cells. PRESENTATION OF CASE:
      This report describes the first case of a pancreatic MCN with no ovarian-type
      stroma in a patient with Turner syndrome (TS). DISCUSSION: The mesenchymal
      component of MCN presumably results from the intra-pancreatic entrapment of
      ovarian stroma during embryogenesis. In our case, the absence of such stromal
      component may relate to the "dysgenetic" changes in the ovary involved in TS.
      CONCLUSION: The present case of primary pancreatic MCN arising in a TS-patient
      triggers some original speculation on the morphogenesis of pancreatic MCN, also
      expanding the current clinico-pathological knowledge of this extremely rare
      entity.

PMID- 24096347
TI  - Dengue fever mimicking acute appendicitis: A case report.
AB  - INTRODUCTION: Dengue fever is an acute viral disease, which usually presents as a
      mild febrile illness. Patients with severe disease present with dengue
      haemorrhagic fever or dengue toxic shock syndrome. Rarely, it presents with
      abdominal symptoms mimicking acute appendicitis. We present a case of a male
      patient presenting with right iliac fossa pain and suspected acute appendicitis
      that was later diagnosed with dengue fever following a negative appendicectomy.
      PRESENTATION OF CASE: A 13-year old male patient presented with fever, localized
      right-sided abdominal pain and vomiting. Abdominal ultrasound was not helpful and
      appendicectomy was performed due to worsening abdominal signs and an elevated
      temperature. A normal appendix with enlarged mesenteric nodes was found at
      surgery. Complete blood count showed thrombocytopenia with leucopenia. Dengue
      fever was now suspected and confirmed by IgM enzyme-linked immunosorbent assay
      against dengue virus. DISCUSSION: This unusual presentation of dengue fever
      mimicking acute appendicitis should be suspected during viral outbreaks and in
      patients with atypical symptoms and cytopenias on blood evaluation in order to
      prevent unnecessary surgery. CONCLUSION: This case highlights the occurrence of
      abdominal symptoms and complications that may accompany dengue fever. Early
      recognition of dengue fever mimicking acute appendicitis will avoid non
      therapeutic operation and the diagnosis may be aided by blood investigations
      indicating a leucopenia, which is uncommon in patients with suppurative acute
      appendicitis.

PMID- 24096349
TI  - Lactobacillus apis sp. nov., from the stomach of honeybees (Apis mellifera),
      having an in vitro inhibitory effect on the causative agents of American and
      European foulbrood.
AB  - A taxonomic study was performed on Gram-stain-positive, catalase-negative and
      regular rod-shaped bacterial strains R4B(T) and R4C, isolated from the stomachs
      of honeybees. 16S rRNA gene sequence analysis revealed that the phylogenetic
      position of the novel strains was within the genus Lactobacillus; the highest
      sequence similarity to R4B(T) was shown by Lactobacillus acidophilus BCRC
      10695(T) (93.6 %). Lower sequence similarities were found to other obligately
      homofermentative lactobacilli. A PCR-DGGE method could detect the sequence of the
      16S rRNA gene of strain R4B(T) at different developmental stages of honeybees
      occurring in two different locations in the Czech Republic. The distinctiveness
      of the strains from other lactobacilli was also confirmed by analysis of
      sequences of other phylogenetic markers applicable to the taxonomy of the genus
      Lactobacillus, ribotyping and rep-PCR analysis. The DNA G+C content of strain
      R4B(T) was 41.3 mol%. The predominant cellular fatty acids of strain R4B(T) were
      C18 : 1omega9c, summed C19 : 1omega6c/C19 : 0 cyclo omega10c, C16 : 0, summed C18
      : 1omega7c/C18 : 1omega6c and summed C16 : 1omega7c/C16 : 1omega6c. The major
      polar lipids of strain R4B(T) were glycolipids, lipids and phospholipids.
      Phenotypic and phylogenetic characteristics also confirmed the independent status
      of the strains at the species level. Interestingly, strain R4B(T) was able to
      inhibit growth in vitro of Paenibacillus larvae subsp. larvae (causal agent of
      American foulbrood in honeybees) and Melissococcus plutonius (causal agent of
      European foulbrood). The name Lactobacillus apis sp. nov. is proposed for this
      novel taxon; the type strain is R4B(T) ( = CCM 8403(T) = LMG 26964(T)). 

PMID- 24096348
TI  - Minireview: applied structural bioinformatics in proteomics.
AB  - The limited sequence similarity of protein sequences with known structures has
      led to an indispensable need for computational technology to predict their
      structures. Structural bioinformatics (SB) has become integral in elucidating the
      sequence-structure-function relationship of a protein. This report focuses on the
      applications of SB within the context of protein engineering including its
      limitation and future challenges. 

PMID- 24096350
TI  - Flavobacterium spartansii sp. nov., a pathogen of fishes, and emended
      descriptions of Flavobacterium aquidurense and Flavobacterium araucananum.
AB  - Two strains (T16(T) and S12) of a Gram-reaction-negative, rod-shaped, yellow
      pigmented bacterium were recovered from kidneys of feral spawning adult Chinook
      salmon (Oncorhynchus tshawytscha) and the gills of captive-reared Chinook salmon
      fingerlings suffering a mortality episode, respectively. Polyphasic
      characterization revealed that these strains possessed gliding motility,
      contained a flexirubin-type pigment, proteolysed multiple substrates (i.e.
      gelatin, casein and elastin), and had a mean DNA G+C content of 35.6 mol%.
      Sequencing of the 16S rRNA gene demonstrated that strains T16(T) and S12 were
      nearly identical to one another (>99% similarity) and were placed within the
      genus Flavobacterium, with Flavobacterium aquidurense CCUG 59847(T) (98.3%),
      Flavobaterium araucananum CCUG 61031(T) (98.2%) and Flavobacterium frigidimaris
      (AB183888, 98.1%) being their closest relatives. Subsequent phylogenetic analyses
      using neighbour-joining, maximum-parsimony and Bayesian methodologies
      demonstrated that strains T16(T) and S12 formed a well-supported clade within the
      genus Flavobacterium that was distinct from other Flavobacterium species. The
      major fatty acid constituents of strains T16(T) and S12 were iso-C15 : 0, C16 :
      1omega6c and/or C16 : 1omega7c, iso-C17 : 0 3-OH, and iso-C15 : 0 3-OH according
      to fatty acid methyl ester analysis. The mean level of DNA-DNA relatedness
      between strain T16(T) and F. aquidurense CCUG 59847(T) and F. araucananum CCUG
      61031(T) was 23 and 29%, respectively. Thus, the data accumulated in this study
      support the suggestion that strains T16(T) and S12 represent a novel species of
      the genus Flavobacterium, for which the name Flavobacterium spartansii sp. nov.
      is proposed. The type strain is T16(T) ( = LMG 27337(T) = ATCC BAA-2541(T)).
      Emended descriptions of F. aquidurense and F. araucananum are also proposed.

PMID- 24096351
TI  - Chitinophaga taiwanensis sp. nov., isolated from the rhizosphere of Arabidopsis
      thaliana.
AB  - An aerobic, Gram-stain-negative, rod-shaped bacterium (strain CC-ALB-1(T)) was
      isolated from the rhizosphere of Arabidopsis thaliana. Strain CC-ALB-1(T) was
      able to grow at 20-30  degrees C, pH 5.0-8.0 and with up to 1.0% (w/v) NaCl. 16S
      rRNA gene sequence analysis showed that strain CC-ALB-1(T) had the highest
      sequence similarity to Chitinophaga ginsengisegetis Gsoil 040(T) (96.9%) and
      Chitinophaga niastensis JS16-4(T) (96.7%); lower levels of similarity (<97.0%)
      were observed to strains of all other species of the genus Chitinophaga. The
      fatty acid profile consisted of iso-C(15 : 0), iso-C(17 : 0) 3-OH, C(15 :
      1)omega5c, C(16 : 1)omega5c and summed feature 3 (C(16 : 1)omega7c and/or C(16 :
      1)omega6c). The polar lipid profile contained phosphatidylethanolamine, two
      unidentified aminolipids and five unidentified lipids. The predominant quinone
      system was menaquinone 7 (MK-7). The DNA G+C content was 53.4 +/- 0.4 mol%. Based
      on its phylogenetic, phenotypic and chemotaxonomic features, strain CC-ALB-1(T)
      is proposed to represent a novel species within the genus Chitinophaga, for which
      the name Chitinophaga taiwanensis sp. nov. is proposed. The type strain is CC-ALB
      1(T) ( = BCRC 80570(T) = JCM 18895(T)).

PMID- 24096352
TI  - Taxonomy, morphology and phylogeny of three new oligotrich ciliates (Protozoa,
      Ciliophora, Oligotrichia) from southern China.
AB  - Oligotrich ciliates are common members of marine microplankton. However, their
      biodiversity is not well documented. In this study, the morphology and
      phylogenetic positions of three new oligotrich species, Spirostrombidium
      apourceolare spec. nov., Spirostrombidium subtropicum spec. nov. and
      Parallelostrombidium conicum spec. nov., collected from coastal habitats of
      southern China, were investigated. Spirostrombidium apourceolare is characterized
      by the girdle kinety which encircles the cell twice as two dextrally oriented
      whorls with some undulations and by the presence of several macronuclear nodules.
      Spirostrombidium subtropicum is recognized by the girdle kinety encircling the
      cell as two dextrally oriented whorls and extrusomes arranged in a stripe along
      the girdle kinety. Parallelostrombidium conicum differs from its congeners by the
      obconic body shape and the posterior portion of the girdle kinety extending
      downwards on the left ventral side to reach the posterior pole. In small-subunit
      rRNA gene trees, S. subtropicum clusters with Omegastrombidium elegans and
      Varistrombidium kielum, and Parallelostrombidium conicum is sister to the clade
      containing Novistrombidium sinicum, Novistrombidium orientale and
      Parallelostrombidium sp. 

PMID- 24096353
TI  - Terriglobus tenax sp. nov., an exopolysaccharide-producing acidobacterium
      isolated from rhizosphere soil of a medicinal plant.
AB  - An exopolysaccharide-producing bacterium, designated strain DRP 35(T), was
      isolated from the rhizosphere soil of a medicinal herb, Angelica sinensis, at
      Geumsan in Korea. Cells were Gram-staining-negative, non-motile, catalase
      positive and oxidase-negative short rods. The isolate grew aerobically from 15 to
      45  degrees C (optimum 30  degrees C), pH 3.5-7.0 (optimum pH 5.0) and in the
      presence of 0-1.0% (w/v) NaCl. Phylogenetic analyses based on 16S rRNA gene
      sequences indicated that strain DRP 35(T) belongs to the genus Terriglobus in the
      phylum Acidobacteria with a sequence similarity of 97.2% and 97.0% to Terriglobus
      saanensis SP1PR4(T) and Terriglobus roseus KBS63(T), respectively. The genomic
      DNA G+C content was 62.1 mol%. DNA-DNA relatedness between strain DRP 35(T) and
      the type strains of the other species of the genus Terriglobus, T. saanensis
      SP1PR4(T) and T. roseus KBS63(T), were 24.6 and 17.2%, respectively. The
      predominant menaquinone was MK-8. Major fatty acids were iso-C(15 : 0), C(16 :
      1)omega7c and C(16 : 0). The polar lipids were phosphatidylethanolamine,
      unidentified aminophospholipid and unknown phospholipids. On the basis of
      polyphasic analysis from this study, strain DRP 35(T) represents a novel species
      of the genus Terriglobus for which the name Terriglobus tenax sp. nov. is
      proposed. The type strain is DRP 35(T) ( = KACC 16474(T) = NBRC 109677(T)).

PMID- 24096354
TI  - Sulfitobacter porphyrae sp. nov., isolated from the red alga Porphyra yezoensis.
AB  - Gram-stain-negative, aerobic, halophilic bacteria, designated SCM-1(T), LCM10-1
      and CTBL-B-147, were isolated from modified half-strength SWM-III medium, PES
      medium and thalli after laboratory cultivation of a red alga, Porphyra yezoensis.
      Phylogenetic analysis of 16S rRNA gene sequences indicated that the new isolates
      were affiliated to the genus Sulfitobacter of the class Alphaproteobacteria, and
      the 16S rRNA gene sequence similarity of the new isolates with the closest
      related species, Sulfitobacter mediterraneus CH-B427(T), was 98.8%. The DNA G+C
      contents of the new isolates were in the range of 61.4-62.3 mol%. DNA-DNA
      relatedness values of strain SCM-1(T) with other type strains of the genus
      Sulfitobacter were less than 15.9%. The new isolates contained Q-10 as the
      predominant ubiquinone, phosphatidylcholine, phosphatidylglycerol, an
      unidentified amino lipid and an unidentified lipid as the main polar lipids, and
      C(18 : 1)omega7c, C(19 : 1)omega7c and C(16 : 0) as the major fatty acids (>10%
      of the total). Strain SCM-1(T) could be differentiated from Sulfitobacter
      mediterraneus JCM 21792(T) by 35 morphological and phenotypic characteristics. On
      the basis of the phylogenetic, genetic and phenotypic properties of the new
      isolates, the name Sulfitobacter porphyrae sp. nov. is proposed, with strain SCM
      1(T) ( = LMG 27110(T) = NBRC 109054(T)) as the type strain.

PMID- 24096355
TI  - Actinomyces haliotis sp. nov., a bacterium isolated from the gut of an abalone,
      Haliotis discus hannai.
AB  - A novel, Gram-staining-positive, facultatively anaerobic, non-motile and coccus
      shaped bacterium, strain WL80(T), was isolated from the gut of an abalone,
      Haliotis discus hannai, collected from the northern coast of Jeju in Korea.
      Optimal growth occurred at 30  degrees C, pH 7-8 and with 1% (w/v) NaCl.
      Phylogenetic analyses based on the 16S rRNA gene sequence revealed that strain
      WL80(T) fell within the cluster of the genus Actinomyces, with highest sequence
      similarity to the type strains of Actinomyces radicidentis (98.8% similarity) and
      Actinomyces urogenitalis (97.0% similarity). The major cellular fatty acids were
      C18 : 1omega9c and C16 : 0. Menaquinone-10 (H4) was the major respiratory
      quinone. The genomic DNA G+C content of the isolate was 70.4 mol%. DNA-DNA
      hybridization values with closely related strains indicated less than 7.6%
      genomic relatedness. The results of physiological, biochemical, chemotaxonomic
      and genotypic analyses indicated that strain WL80(T) represents a novel species
      of the genus Actinomyces, for which the name Actinomyces haliotis sp. nov. is
      proposed. The type strain is WL80(T) ( = KACC 17211(T) = JCM 18848(T)).

PMID- 24096356
TI  - Pseudoalteromonas xiamenensis sp. nov., a marine bacterium isolated from coastal
      surface seawater.
AB  - A Gram-negative, oxidase- and catalase-positive, rod-shaped, non-spore-forming,
      motile, aerobic bacterium, designated Y2(T), was isolated from surface seawater
      of Yundang Lake, Xiamen, China. The strain was able to grow in the presence of
      0.5-6.0% NaCl (optimum 1.0-1.5%), at pH 5-10 (optimum pH 8) and at 10-40  degrees
      C (optimum 25  degrees C). Phylogenetic analysis based on 16S rRNA gene sequences
      indicated that strain Y2(T) belongs to the genus Pseudoalteromonas, with the
      highest sequence similarity of 94.9% to Pseudoalteromonas tunicata D2(T); within
      the genus Pseudoalteromonas, it showed the lowest similarity of 92.8% to
      Pseudoalteromonas denitrificans ATCC 43337(T). The G+C content of the chromosomal
      DNA of strain Y2(T) was 45.1 mol%. The predominant fatty acids were summed
      feature 3 (C(16 : 1)omega6c and/or C(16 : 1)omega7c), C(16 : 0), C(12 : 0) 3-OH
      and summed feature 8 (C(18 : 1)omega6c and/or C(18 : 1)omega7c). The only
      respiratory quinone detected was Q-8. Based on the phylogenetic and phenotypic
      characteristics, strain Y2(T) represents a novel species of the genus
      Pseudoalteromonas, for which the name Pseudoalteromonas xiamenensis sp. nov. is
      proposed; the type strain is Y2(T) ( = CGMCC 1.12157(T) = JCM 18779(T)).

PMID- 24096357
TI  - Methyloceanibacter caenitepidi gen. nov., sp. nov., a facultatively
      methylotrophic bacterium isolated from marine sediments near a hydrothermal vent.
AB  - A moderately thermophilic, methanol-oxidizing bacterium (strain Gela4(T)) was
      isolated from methane-utilizing mixed-culture originating from marine sediment
      near a hydrothermal vent. Phylogenetic analysis of 16S rRNA gene sequences
      indicated that strain Gela4(T) was closely related to members of the genus
      'Methyloligella' (94.7% similarity) within the class Alphaproteobacteria. Strain
      Gela4(T) was a Gram-staining-negative and aerobic organism. Cells were rod-shaped
      and non-motile. The temperature range for growth of strain Gela4(T) was 19-43 
      degrees C (optimal growth at 35  degrees C). Strain Gela4(T) tolerated up to 9%
      NaCl with an optimum at 1%. The organism was a facultative methylotroph that
      could utilize methanol, methylamine, trimethylamine and a variety of multi-carbon
      compounds. The major cellular fatty acid and major respiratory quinone were C18 :
      1omega7c and ubiquinone-10, respectively. The predominant phospholipids were
      phosphatidylcholine, phosphatidylglycerol and phosphatidylethanolamine. The DNA
      G+C content was 63.9 mol%. On the basis of the morphological, physiological,
      biochemical and genetic information, a novel genus and species,
      Methyloceanibacter caenitepidi is proposed, with Gela4(T) ( = NBRC 109540(T) =
      DSM 27242(T)) as the type strain.

PMID- 24096358
TI  - Wenyingzhuangia marina gen. nov., sp. nov., a member of the family
      Flavobacteriaceae isolated from a recirculating mariculture system.
AB  - A Gram-stain-negative, strictly aerobic and heterotrophic bacterial strain,
      designed strain D1(T), was isolated from a recirculating mariculture system in
      Tianjin, China. Its taxonomic position was determined using a polyphasic
      approach. Cells of strain D1(T) were non-flagellated short rods, 0.3-0.5 um wide
      and 0.5-1.0 um long. Growth was observed at 15-30  degrees C (optimum, 25 
      degrees C), at pH 5.5-9.0 (optimum, pH 6.5-7.0) and in the presence of 1-8% (w/v)
      NaCl (optimum, 2-3 %). Cells contained carotenoid pigments but not flexirubin
      type pigments. Strain D1(T) contained MK-6 as the sole menaquinone and
      phosphatidylethanolamine (PE) as the sole phospholipid and four unidentified
      lipids. The major cellular fatty acids (>10%) were iso-C15 : 0 (23.2 %), iso-C17
      : 0 3-OH (15.2%), C(16 : 1)omega7c/C(16 : 1)omega6c (14.3%), iso-C(15 : 0) 3-OH
      (13.5%) and iso-C15 : 1 G (10.8%). 16S rRNA gene sequence analyses indicated that
      strain D1(T) belonged to the family Flavobacteriaceae and showed closest
      phylogenetic relationship to the genus Lutibacter, with highest sequence
      similarity to Lutibacter aestuarii MA-My1(T) (92.2%). The DNA G+C content of
      strain D1(T) was 35.9 mol%. On the basis of phenotypic, chemotaxonomic and
      phylogenetic data, strain D1(T) was considered to represent a novel species in a
      new genus of the family Flavobacteriaceae, for which the name Wenyingzhuangia
      marina gen. nov., sp. nov. is proposed. The type strain of the type species is
      D1(T) ( = CGMCC 1.12162(T) = JCM 18494(T)).

PMID- 24096359
TI  - Photobacterium aquae sp. nov., isolated from a recirculating mariculture system.
AB  - A Gram-staining-negative, heterotrophic, facultatively anaerobic bacterium,
      designated AE6(T), was isolated from a grouper (Epinephelus malabaricas) culture
      tank in a recirculating mariculture system located in Tianjin, China. Strain
      AE6(T) was able to grow at 15-40  degrees C (optimum, 30-35  degrees C), at pH
      5.5-10.0 (optimum, pH 7.0-7.5) and in the presence of 0.5-7% (w/v) NaCl (optimum,
      2-3%). It contained Q-8 as the predominant respiratory quinone,
      phosphatidylethanolamine (PE) and phosphatidylglycerol (PG) as the major polar
      lipids and C(16 : 1)omega7c/C(16 : 1)omega6c (40.4%), C(18 : 1)omega7c (15.5%)
      and C(16 : 0) (13.5%) as the predominant cellular fatty acids. The genomic DNA
      G+C content was 47.1 mol%. Phylogenetic analysis based on 16S rRNA gene sequences
      revealed that strain AE6(T) belonged to the genus Photobacterium (94.2-96.8% of
      16S rRNA gene sequence similarity) and formed a distinct phylogenetic lineage
      within the genus and exhibited the highest sequence similarity to Photobacterium
      aphoticum CECT 7614(T) (96.8%). Multilocus sequence analysis (MLSA) using four
      loci (gyrB, rpoA, pyrH and recA) also revealed that strain AE6(T) was
      phylogenetically related to the genus Photobacterium. Based on the phylogenetic,
      chemotaxonomic and phenotypic evidence, strain AE6(T) is considered to represent
      a novel species of the genus Photobacterium, for which the name Photobacterium
      aquae sp. nov. is proposed. The type strain is AE6(T) ( = CGMCC 1.12159(T) = JCM
      18480(T)).

PMID- 24096360
TI  - Mortality and health services utilisation among older people with advanced
      cognitive impairment living in residential care homes.
AB  - OBJECTIVES: To study the demography, clinical characteristics, service
      utilisation, mortality, and predictors of mortality in older residential care
      home residents with advanced cognitive impairment. DESIGN: Cohort longitudinal
      study. SETTING: Residential care homes for the elderly in Hong Kong West.
      PARTICIPANTS: Residents of such homes aged 65 years or more with advanced
      cognitive impairment. RESULTS: In all, 312 such residential care home residents
      (71 men and 241 women) were studied. Their mean age was 88 (standard deviation,
      8) years and their mean Barthel Index 20 score was 1.5 (standard deviation, 2.0).
      In all, 164 (53%) were receiving enteral feeding. Nearly all of them had urinary
      and bowel incontinence. Apart from Community Geriatric Assessment Team clinics,
      119 (38%) of the residents attended other clinics outside their residential care
      homes. In all, 107 (34%) died within 1 year; those who died within 1 year used
      significantly more emergency and hospital services (P<0.001), and utilised more
      services from community care nurses for wound care (P=0.001), enteral feeding
      tube care (P=0.018), and urinary catheter care (P<0.001). Independent risk
      factors for 1-year mortality were active pressure sores (P=0.0037), enteral
      feeding (P=0.008), having a urinary catheter (P=0.0036), and suffering from
      chronic obstructive pulmonary disease (P=0.011). A history of pneumococcal
      vaccination was protective with respect to 1-year mortality (P=0.004).
      CONCLUSION: Residents of residential care homes for the elderly with advanced
      cognitive impairment were frail, exhibited multiple co-morbidities and high
      mortality. They were frequent users of out-patient, emergency, and in-patient
      services. The development of end-of-life care services in residential care homes
      for the elderly is an important need for this group of elderly.

PMID- 24096361
TI  - Patients' perceptions of day surgery: a survey study in China surgery.
AB  - OBJECTIVE: To investigate patients' perceptions of day surgery, specifically
      their convenience; social, functional and economic values; risk perceptions; and
      patient satisfaction. DESIGN: Cross-sectional questionnaire survey. SETTING: West
      China Hospital in Chengdu City, China. PARTICIPANTS: All the day-surgery patients
      admitted to the Centre for Day Surgery in December 2011. MAIN OUTCOME MEASURES:
      Demographic profiles, each patient's value and risk perceptions about day
      surgery, as well as overall satisfaction with day surgery. RESULTS: Convenience
      value and social value were emphasised by 87% and 60% of the 153 valid
      respondents, respectively. Comparatively speaking, functional and economic value
      were respectively chosen by 50% and 43% of the respondents, while 75% worried
      about postoperative complications and adverse events, only 53% and 27% worried
      about rehabilitation knowledge and psychological risks, respectively. More than
      95% of the respondents were satisfied with the clinic service and staff
      attitudes, hospital surgery environment, operating skills and results, but fewer
      (84%) were satisfied with the communication processes surrounding day surgery.
      CONCLUSION: Patients exhibited high acceptance and satisfaction regarding day
      surgery. The convenience experienced by patients and their families is the main
      perceived value of day surgery. Nevertheless, during the recovery process
      patients are concerned about possible adverse events, treatment of postoperative
      complications, and lack of information. These aspects of care delivery warrant
      improvement through redesign of the day surgery service.

PMID- 24096362
TI  - Lymphoscintigraphy in the evaluation of lower extremity lymphedema: local
      experience.
AB  - OBJECTIVE: To review our local experience in the use of lymphoscintigraphy to
      evaluate lymphedema of the lower extremities. DESIGN: Retrospective case series.
      SETTING: A local regional hospital in Hong Kong. PATIENTS: Images and records of
      all patients presenting to our hospital with suspected lower limb lymphedema from
      1998 to 2011 for whom lymphoscintigraphy was performed were reviewed. MAIN
      OUTCOME MEASURES: Lymphoscintigraphy findings and clinical outcomes. RESULTS: In
      all, 24 patients (13 males and 11 females; age range, 14-83 years) had undergone
      lymphoscintigraphy for suspected lower limb lymphedema. Eight cases were
      confirmed positive, including one with lymphangiectasia, five with lymphatic
      obstruction, and two with lymphatic leakage. No complication was encountered.
      CONCLUSION: Lymphoscintigraphy is safe and effective for the evaluation of
      lymphedema in lower extremities.

PMID- 24096363
TI  - Live visualization of chromatin dynamics with fluorescent TALEs.
AB  - The spatiotemporal organization of genomes in the nucleus is an emerging key
      player to regulate genome function. Live imaging of nuclear organization dynamics
      would be a breakthrough toward uncovering the functional relevance and mechanisms
      regulating genome architecture. Here, we used transcription activator-like
      effector (TALE) technology to visualize endogenous repetitive genomic sequences.
      We established TALE-mediated genome visualization (TGV) to label genomic
      sequences and follow nuclear positioning and chromatin dynamics in cultured mouse
      cells and in the living organism. TGV is highly specific, thus allowing
      differential labeling of parental chromosomes by distinguishing between single
      nucleotide polymorphisms (SNPs). Our findings provide a framework to address the
      function of genome architecture through visualization of nuclear dynamics in
      vivo. 

PMID- 24096364
TI  - Analysis of microRNA-target interactions across diverse cancer types.
AB  - Little is known about the extent to which individual microRNAs (miRNAs) regulate
      common processes of tumor biology across diverse cancer types. Using molecular
      profiles of >3,000 tumors from 11 human cancer types in The Cancer Genome Atlas,
      we systematically analyzed expression of miRNAs and mRNAs across cancer types to
      infer recurrent cancer-associated miRNA-target relationships. As we expected, the
      inferred relationships were consistent with sequence-based predictions and
      published data from miRNA perturbation experiments. Notably, miRNAs with
      recurrent target relationships were frequently regulated by genetic and
      epigenetic alterations across the studied cancer types. We also identify new
      examples of miRNAs that coordinately regulate cancer pathways, including the miR
      29 family, which recurrently regulates active DNA demethylation pathway members
      TET1 and TDG. The online resource http://cancerminer.org allows exploration and
      prioritization of miRNA-target interactions that potentially regulate
      tumorigenesis. 

PMID- 24096365
TI  - Structure of human mitochondrial RNA polymerase elongation complex.
AB  - Here we report the crystal structure of the human mitochondrial RNA polymerase
      (mtRNAP) transcription elongation complex, determined at 2.65-A resolution. The
      structure reveals a 9-bp hybrid formed between the DNA template and the RNA
      transcript and one turn of DNA both upstream and downstream of the hybrid.
      Comparisons with the distantly related RNA polymerase (RNAP) from bacteriophage
      T7 indicates conserved mechanisms for substrate binding and nucleotide
      incorporation but also strong mechanistic differences. Whereas T7 RNAP refolds
      during the transition from initiation to elongation, mtRNAP adopts an
      intermediary conformation that is capable of elongation without refolding. The
      intercalating hairpin that melts DNA during T7 RNAP initiation separates RNA from
      DNA during mtRNAP elongation. Newly synthesized RNA exits toward the
      pentatricopeptide repeat (PPR) domain, a unique feature of mtRNAP with conserved
      RNA-recognition motifs. 

PMID- 24096367
TI  - Secondary health conditions in persons with spinal cord injury: a longitudinal
      study from one to five years post-discharge.
AB  - OBJECTIVE: To assess the occurrence of secondary health conditions and their
      potential risk factors in persons with spinal cord injury from 1 to 5 years after
      discharge from initial inpatient rehabilitation. DESIGN: Multicentre longitudinal
      study. SUBJECTS: A total of 139 wheelchair-dependent persons with spinal cord
      injury. METHODS: The occurrence of secondary health conditions and their
      potential risk factors were assessed in a clinical interview with a
      rehabilitation physician at 1 and 5 years after discharge from inpatient
      rehabilitation and by a telephone interview 2 years after discharge. Self-report
      questionnaires were used for the assessment of musculoskeletal and neuropathic
      pain. RESULTS: Neuropathic pain (83.7-92.1%), musculoskeletal pain (62.3-87.1%)
      and urinary tract infection (56.5-58.9%) were the most frequently reported
      secondary health conditions. The occurrence of several secondary health
      conditions was higher among women and individuals with a complete lesion,
      tetraplegia, and with a higher body mass index. CONCLUSION: Secondary health
      conditions are common in the first years post-discharge following spinal cord
      injury, and their course seems to be relatively stable. These results emphasize
      the number of health issues that must be considered during post-injury care of
      persons with spinal cord injury living in the community, and the importance of a
      well-coordinated interdisciplinary approach from specialized rehabilitation
      centres.

PMID- 24096368
TI  - Family cognitive remediation therapy for anorexia nervosa.
AB  - Anorexia nervosa (AN) in childhood and adolescence has a poor prognosis. It is
      possible that this may in part be due to the fact that cognitive weaknesses that
      appear to be risk factors for its development and maintenance are not being
      targeted in treatment. Through its focus on these deficits, cognitive remediation
      therapy (CRT) has been shown to be a promising intervention for AN. Furthermore,
      family interventions are widely recommended for this patient population, but to
      date no studies have reported the use of CRT in a family setting. This paper
      presents a case series in which family-based CRT was a significant component of
      the management. It was well received by patients and their families and
      previously treatment resistant patients became more engaged with the entire
      treatment process. In addition, all patients receiving family-based CRT went on
      to make progress towards recovery. These initial clinical observations suggest
      family-based CRT is likely to be a useful addition to treatment for child and
      adolescent AN and justifies formal evaluation. 

PMID- 24096366
TI  - Age and psychological influences on immune responses to trivalent inactivated
      influenza vaccine in the meditation or exercise for preventing acute respiratory
      infection (MEPARI) trial.
AB  - BACKGROUND: Strategies to improve influenza vaccine protection among elderly
      individuals are an important research priority. Mindfulness-based stress
      reduction (MBSR) and exercise have been shown to affect aspects of immune
      function in some populations. We hypothesized that influenza vaccine responses
      may be enhanced with meditation or exercise training as compared with controls.
      RESULTS: No differences in vaccine responses were found comparing control to MBSR
      or exercise. Individuals achieving seroprotective levels of influenza antibody
      >=160 units had higher optimism, less anxiety, and lower perceived stress than
      the nonresponders. Age correlated with influenza antibody responses, but not with
      IFNgamma or IL-10 production. CONCLUSION: The MBSR and exercise training
      evaluated in this study failed to enhance immune responses to influenza vaccine.
      However, optimism, perceived stress, and anxiety were correlated in the expected
      directions with antibody responses to influenza vaccine. METHODS: Healthy
      individuals>=50 y were randomly assigned to exercise (n=47) or MBSR (n=51)
      training or a waitlist control condition (n=51). Each participant received
      trivalent inactivated influenza vaccine after 6 weeks, and had blood draws prior
      to and 3 and 12 weeks after immunization. Serum influenza antibody, nasal
      immunoglobulin A, and peripheral blood mononuclear cell interferon-gamma
      (IFNgamma) and interleukin-10 (IL-10) concentrations were measured. Measures of
      optimism, perceived stress, and anxiety were obtained over the course of the
      study. Seroprotection was defined as an influenza antibody concentration>=160
      units. Vaccine responses were compared using ANOVA, t tests, and Kruskal-Wallis
      tests. The correlation between vaccine responses and age was examined with the
      Pearson test.

PMID- 24096369
TI  - Characteristics of suicide notes of children and young adolescents: an
      examination of the notes from suicide victims 15 years and younger.
AB  - OBJECTIVE: By analysing the suicide notes from suicide victims 15 years and
      younger, we attempt to gain insight into the process leading to youth suicide and
      explore the characteristics of the note writers. METHOD: During a psychological
      autopsy on 42 youths, we were entrusted with 23 suicide notes in which we
      explored the themes and compared the note writers to the non-note writers.
      RESULTS: The key messages were as follows: explain the reason for suicide,
      declare love and give instructions. The note writers had showed suicidal
      behaviour more frequently than non-note writers. CONCLUSION: In the notes from
      youth suicide victims they present themselves as fully responsible and without
      confusion or overwhelming despair. The notes are likely equally informative as
      the notes of older victims.

PMID- 24096370
TI  - Second malignancies in long-term testicular cancer survivors.
AB  - PURPOSE: The objective of the present study is to analyze long-term testicular
      cancer (TC) survivors focusing on the correlation of therapeutic modalities used,
      the age of patients and second malignancy (SM) occurrence. PATIENTS AND METHODS:
      A total of 1,367 patients with TC and different subsequent therapeutic procedures
      were followed up between 1970 and 2012. The occurrence of SM was analyzed by
      standard incidence ratios (SIR). SM occurred in 96 (7.0 %) patients with primary
      TC. RESULTS: The most frequent SM was TC (SIR 27.4, n = 64); a significantly
      higher occurrence was observed after primary testicular seminoma. Prostate cancer
      appeared in 10 patients (SIR 5.2), with a mean age 54.9 years, while the typical
      age of patients in Slovakia was 71.4 years. Kidney cancer developed in 6
      patients, a significant higher SIR was registered only after primary non
      seminomas. The mean patient's age was 48.5 years, while the typical age of all
      male patients in Slovakia was 62.4 years. Other SM had no significantly higher
      SIR. Colorectal cancer appeared in 8 patients with primary TC, with a mean age
      56.0 years, while the typical age of male patients with primary colorectal cancer
      in Slovakia was 67.1 years. Other non-testicular tumors appeared in 8 patients.
      SM occurs in 1.5 % of patients following orchiectomy alone, in 4.3 % following
      radiotherapy, 5.0 % following chemotherapy and in 4.4 % following combined chemo
      radiotherapy. CONCLUSIONS: Preliminary analyses indicate increased SM occurrence
      in patients with primary TC in comparison with the general population, and it
      also occurs in younger age at the time of SM diagnosis.

PMID- 24096371
TI  - Sodium gradient, xerostomia, thirst and inter-dialytic excessive weight gain: a
      possible relationship with hyposalivation in patients on maintenance
      hemodialysis.
AB  - PURPOSE: The aim of the study was to assess whether hyposalivation is linked with
      increased thirst sensation and weight gain in hemodialysis (HD) patients and
      whether there is any connection between hyposalivation and sodium balance.
      METHODS: One hundred and eleven participants (64 males and 47 females) receiving
      maintenance hemodialysis, mean age 59.1 +/- 13.6 years old, were involved in the
      study. All participants completed a survey evaluating thirst intensity (DTI) and
      xerostomia inventory (XI). In addition, pre-dialysis sodium concentration and
      inter-dialytic weight gain (IWG) were assessed. The division into no
      hyposalivation and hyposalivation groups was based on an unstimulated whole
      saliva (UWS) flow rate. RESULTS: Hyposalivation, UWS below 0.1 mL/min, was
      reported in 28.8% of HD patients. In these participants, IWG was higher than in
      patients with UWS > 0.1 mL/min (3.65 +/- 1.78 vs 3.0 +/- 1.4; p = 0.042), as well
      as the pre-dialysis sodium gradient (3.22 +/- 2.1 vs 1.6 +/- 2.8; p = 0.031). The
      mean XI and DTI scores did not differ between study groups. In the hyposalivation
      group, pre-dialysis sodium serum gradient negatively correlated with saliva
      outflow (rho = -0.61, p = 0.019) and positively with IWG (rho = 0.49, p = 0.022).
      IWG correlated with XI (rho = 0.622, p = 0.016) in hyposalivation group and with
      DTI in no-hyposalivation group (rho = 0.386, p = 0.033). CONCLUSIONS:
      Hyposalivation significantly correlates with IWG; however, its influence on
      thirst and self-reported mouth dryness seems to be weaker than expected.
      Additionally, hyposalivation was found to be associated with an elevated pre
      dialysis sodium gradient.

PMID- 24096372
TI  - Mechanical processing of hyperviscous semen specimens can negatively affect sperm
      DNA fragmentation.
AB  - INTRODUCTION: The present study compared the DNA fragmentation in human sperm
      samples with reduced, physiological, and increased viscosity in order to evaluate
      whether the process used to reduce viscosity (expulsion of semen through a needle
      and syringe) alters significantly sperm DNA fragmentation. METHODS: The seminal
      parameters of semen samples from 123 patients were evaluated and classified
      according to their viscosity. Samples with increased viscosity were submitted to
      a process of expulsion of semen through a 10-mL syringe and an 18-gauge (18G)
      needle to reduce the seminal viscosity. The DNA fragmentation of all samples was
      analysed using TUNEL assay (Terminal deoxynucleotidyl transferase mediated dUTP
      Nick-end labelling assay); in samples with increased viscosity, the fragmentation
      was assessed before and after the process of expulsion with syringe and needle.
      RESULTS: There was no difference in DNA fragmentation between groups with
      different viscosity (P = 0.857). A significantly increase in sperm DNA
      fragmentation after expulsion of hyperviscous semen through the syringe was
      observed (P = 0.035). CONCLUSION: There was no difference in DNA fragmentation
      rate between samples with reduced, increased and physiological viscosities;
      however, the physical process of expulsion of semen through a syringe and needle
      increased sperm DNA fragmentation.

PMID- 24096373
TI  - The value of the 2005 International Society of Urological Pathology (ISUP)
      modified Gleason grading system as a predictor of biochemical recurrence after
      radical prostatectomy.
AB  - PURPOSE: To compare time and risk to biochemical recurrence (BR) after radical
      prostatectomy of two chronologically different groups of patients using the
      standard and the modified Gleason system (MGS). METHODS: Cohort 1 comprised
      biopsies of 197 patients graded according to the standard Gleason system (SGS) in
      the period 1997/2004, and cohort 2, 176 biopsies graded according to the modified
      system in the period 2005/2011. Time to BR was analyzed with the Kaplan-Meier
      product-limit analysis and prediction of shorter time to recurrence using
      univariate and multivariate Cox proportional hazards model. RESULTS: Patients in
      cohort 2 reflected time-related changes: striking increase in clinical stage T1c,
      systematic use of extended biopsies, and lower percentage of total length of
      cancer in millimeter in all cores. The MGS used in cohort 2 showed fewer biopsies
      with Gleason score <= 6 and more biopsies of the intermediate Gleason score 7.
      Time to BR using the Kaplan-Meier curves showed statistical significance using
      the MGS in cohort 2, but not the SGS in cohort 1. Only the MGS predicted shorter
      time to BR on univariate analysis and on multivariate analysis was an independent
      predictor. CONCLUSIONS: The results favor that the 2005 International Society of
      Urological Pathology modified system is a refinement of the Gleason grading and
      valuable for contemporary clinical practice.

PMID- 24096374
TI  - Long-term experiment to study the development, interaction, and influencing
      factors of DEXA parameters.
AB  - Dual-energy X-ray absorption (DEXA) is commonly used to measure bone mineral
      density (BMD), bone mineral content (BMC), and body composition data (fat mass
      and lean mass) for phenotype assessment in mice. We were interested in the long
      term development of BMD, BMC, lean mass, and fat mass of mice, also taking into
      account sex and genetic background. The dataset was used to analyze correlations
      among the different parameters. We analyzed males and females from inbred strains
      C3HeB/FeJ and C57BL/6J, starting from 42 until 528 days of age. To evaluate the
      effect of husbandry systems, we repeated a part of the study in a second facility
      with a different caging system. We also assessed different DEXA settings and
      repeatability of the scans. The results of this study were used to draw
      conclusions for the use of DEXA analysis in mouse phenotyping approaches. 

PMID- 24096376
TI  - Dispersant-free conducting pastes for flexible and printed nanocarbon electrodes.
AB  - The dispersant-free fabrication of highly conducting pastes based on organic
      solvents with nanocarbon materials such as carbon nanotubes and graphene
      nanoplatelets has been hindered by severe agglomeration. Here we report a
      straightforward method for fabricating nanocarbon suspensions with >10% weight
      concentrations in absence of organic dispersants. The method involves introducing
      supramolecular quadruple hydrogen-bonding motifs into the nanocarbon materials
      without sacrificing the electrical conductivity. Printed films of these materials
      show high electrical conductivity of ~500,000 S m(-1) by hybridization with 5
      vol% silver nanowires. In addition, the printed nanocarbon electrodes provide
      high-performance alternatives to the platinum catalytic electrodes commonly used
      in dye-sensitized solar cells and electrochemical electrodes in supercapacitors.
      The judicious use of supramolecular interactions allows fabrication of printable,
      spinnable and chemically compatible conducting pastes with high-quality
      nanocarbon materials, useful in flexible electronics and textile electronics.

PMID- 24096375
TI  - Crybb2 coding for betaB2-crystallin affects sensorimotor gating and hippocampal
      function.
AB  - betaB2-crystallin (gene symbol: Crybb2/CRYBB2) was first described as a
      structural protein of the ocular lens. This gene, however, is also expressed in
      several regions of the mammalian brain, although its function in this organ
      remains entirely unknown. To unravel some aspects of its function in the brain,
      we combined behavioral, neuroanatomical, and physiological analyses in a novel
      Crybb2 mouse mutant, O377. Behavioral tests with male O377 mutants revealed
      altered sensorimotor gating, suggesting modified neuronal functions. Since these
      mouse mutants also displayed reduced hippocampal size, we concentrated further
      investigations on the hippocampus. Free intracellular Ca(2+) levels were
      increased and apoptosis was enhanced in the hippocampus of O377 mutants.
      Moreover, the expression of the gene encoding calpain 3 (gene symbol Capn3) was
      elevated and the expression of genes coding for the NMDA receptor subunits was
      downregulated. Additionally, the number of parvalbumin-positive interneurons was
      decreased in the hippocampus but not in the cortex of the mutants. High-speed
      voltage-sensitive dye imaging demonstrated an increased translation of input-to
      output neuronal activity in the dentate gyrus of this Crybb2 mutant. These
      results point to an important function of betaB2-crystallin in the hippocampal
      network. They indicate pleiotropic effects of mutations in the Crybb2 gene, which
      previously had been considered to be specific to the ocular lens. Moreover, our
      results are the first to demonstrate that betaB2-crystallin has a role in
      hippocampal function and behavioral phenotypes. This model can now be further
      explored by future experiments. 

PMID- 24096377
TI  - Accuracy and reliability of determining the isometric point of the knee for
      multiligament knee reconstruction.
AB  - PURPOSE: To compare the accuracy and reliability of the anatomic and radiographic
      techniques for identifying the isometric point of the knee. METHODS: Only four
      specimens were used; however, eight experienced multiligament knee injury
      surgeons were recruited to address this limitation. Surgeons estimated the
      isometric point (EIP) on the medial and lateral sides using an anatomic and
      radiographic method. The x and y coordinates of the EIP were compared to the true
      isometric point (TIP). T-tests and interclass correlation coefficients (ICC) were
      performed to determine the accuracy and reliability between the methods. RESULTS:
      There was no difference in placement of the EIP on the medial side of the knee in
      the anterior/posterior (x; p = n.s.) and superior/inferior direction (y; p =
      n.s). The EIP was anterior (p = 0.001) to the TIP with the radiographic method on
      the lateral side and approached significance (p = 0.05) in the superior/inferior
      direction. The ICC (95% CI) for identifying the EIP on the medial side in the
      anterior/posterior direction using the anatomic method was 0.64 (0.28-0.96) and
      0.11 (-0.06 to 0.77) in the superior/inferior direction. Using the radiographic
      method, the ICC in the anterior/posterior and superior/inferior direction was
      0.49 (0.14-0.94) and 0.15 (-0.47 to 0.81), respectively. On the lateral side, the
      ICC for the anatomic method was 0.84 (0.56-0.99) in the anterior/posterior
      direction and 0.36 (0.05-0.90) in the superior/inferior direction. Using the
      radiographic method, the ICC in the anterior/posterior and superior/inferior
      direction was 0.61 (0.26-0.96) and 0.89 (0.67-0.99), respectively. CONCLUSIONS:
      There was no difference in accuracy on the medial side of the knee. On the
      lateral side, the anatomic method was more accurate in the anterior/posterior
      direction. Reliability was greater in the anterior/posterior direction on both
      sides of the knee. Surgeons were most likely to place the isometric point
      anterior and superior to the TIP on both the medial and lateral sides of the knee
      with either method which has the potential to cause graft lengthening. This
      should be taken into consideration during reconstruction/repair of the MCL/PMC
      and LCL/PLC.

PMID- 24096378
TI  - A rare type of secondary cancer in a child with acute lymphoblastic leukemia:
      malignant fibrous histiocytoma.
AB  - Secondary cancers which are related with treatment of childhood acute
      lymphoblastic leukemia (ALL) is a significant problem with longer term. For
      development of secondary cancer after treatment, the latency period varies
      between 5 and 10 years. In this case, a 13 year-old-boy diagnosed as high-risk
      ALL was treated with chemotherapy and prophylactic cranial radiotherapy at a dose
      of 1800 cGy. Six years after the end of treatment he developed a 5 * 5 * 4 cm
      mass at the right temporal region of the cranium. The mass was excised totally
      with clear surgical margin. Pathology of mass has been diagnosed as malignant
      fibrous histiocytoma (MFH), recently referred to as an undifferentiated
      pleomorphic sarcoma (UPS). After treatment of childhood ALL, reported cases of
      secondary MFH is extremely rare in the literature. Herein we present a case of
      MFH/UPS that developed as a secondary cancer 6 years after the end of ALL
      treatment.

PMID- 24096379
TI  - Feeling superior is a bipartisan issue: extremity (not direction) of political
      views predicts perceived belief superiority.
AB  - Accusations of entrenched political partisanship have been launched against both
      conservatives and liberals. But is feeling superior about one's beliefs a
      partisan issue? Two competing hypotheses exist: the rigidity-of-the-right
      hypothesis (i.e., conservatives are dogmatic) and the ideological-extremism
      hypothesis (i.e., extreme views on both sides predict dogmatism). We measured 527
      Americans' attitudes about nine contentious political issues, the degree to which
      they thought their beliefs were superior to other people's, and their level of
      dogmatism. Dogmatism was higher for people endorsing conservative views than for
      people endorsing liberal views, which replicates the rigidity-of-the-right
      hypothesis. However, curvilinear effects of ideological attitude on belief
      superiority (i.e., belief that one's position is more correct than another's)
      supported the ideological-extremism hypothesis. Furthermore, responses reflecting
      the greatest belief superiority were obtained on conservative attitudes for three
      issues and liberal attitudes for another three issues. These findings capture
      nuances in the relationship between political beliefs and attitude entrenchment
      that have not been revealed previously. 

PMID- 24096380
TI  - At the Bedside: Innate immunity as an immunotherapy tool for hematological
      malignancies.
AB  - The identification of an anti-tumor effect displayed by cells of innate immunity
      has opened new scenarios, not only in the field of allo-HSCT but also for
      nontransplanted patients with hematological malignancies or solid tumors. Donor
      derived NK cells have been shown to contribute to the eradication of malignant
      cells after allo-HSCT, when recipients lack ligands for their inhibitory
      receptors. These alloreactive donor NK cells can also kill recipient APCs and
      CTLs, thus preventing the occurrence of GvHD and graft rejection. The role of
      activating receptors on the capacity of NK cells to kill leukemia targets has
      become evident in the last years. The adoptive infusion of ex vivo-activated NK
      cells has been investigated recently in Phase I/II trials on patients with
      hematological malignancies and solid tumors, with promising results. gammadelta T
      lymphocytes are also able to display anti-tumor activity-this providing the
      biological rationale for Phase I/II trials in lymphoproliferative disorders and
      solid tumors. Aminobisphosphonates are clinically available compounds able to
      boost gammadelta T cell function. As gammadelta T cells do not cause GvHD, they
      could also be transduced with tumor-associated chimeric antigen receptors and
      safely infused in allo-HSCT recipients. Basic aspects of innate immunity relevant
      to the field will be covered by a companion review article. 

PMID- 24096381
TI  - Loss of hippocampal interneurons and epileptogenesis: a comparison of two animal
      models of acquired epilepsy.
AB  - Reduced hippocampal GABAergic inhibition is acknowledged to be associated with
      epilepsy. However, there are no studies that had quantitatively compared the loss
      of various interneuron populations in different models of epilepsy. We tested a
      hypothesis that the more severe the loss of hippocampal interneurons, the more
      severe was the epilepsy. Epileptogenesis was triggered in adult rats by status
      epilepticus (SE) (56 SE, 24 controls) or by traumatic brain injury (TBI) (45 TBI,
      23 controls). The total number of hippocampal parvalbumin (PARV), cholecystokinin
      (CCK), calretinin (CR), somatostatin (SOM), or neuropeptide Y (NPY) positive
      neurons was estimated using unbiased stereology at 1 or 6 months post-insult. The
      rats with TBI had no spontaneous seizures but showed increased seizure
      susceptibility. Eleven of the 28 rats (39 %) in the SE group had spontaneous
      seizures. The most affected hippocampal area after TBI was the ipsilateral
      dentate gyrus, where 62 % of PARV-immunoreactive (ir) (p < 0.001 compared to
      controls), 77 % of CR-ir (p < 0.05), 46 % of SOM-ir (p < 0.001), and 59 % of NPY
      ir (p < 0.001) cells remained at 1 month after TBI. At 6 months post-TBI, only 35
      % of PARV-ir (p < 0.001 compared to controls), 63 % of CCK-ir (p < 0.01), 74 % of
      CR-ir (p < 0.001), 55 % of SOM-ir (p < 0.001), and 51 % of NPY-ir (p < 0.001)
      cells were remaining. Moreover, the reduction in PARV-ir, CCK-ir, and CR-ir
      neurons was bilateral (all p < 0.05). Substantial reductions in different
      neuronal populations were also found in subfields of the CA3 and CA1. In rats
      with epilepsy after SE, the number of PARV-ir neurons was reduced in the
      ipsilateral CA1 (80 % remaining, p < 0.05) and the number of NPY-ir neurons
      bilaterally in the dentate gyrus (33-37 %, p < 0.01) and the CA3 (54-57 %, p <
      0.05). Taken together, interneuron loss was substantially more severe,
      widespread, progressive, and included more interneuron subclasses after TBI than
      after SE. Interneurons responsible for perisomatic inhibition were more
      vulnerable to TBI than those providing dendritic inhibition. Unlike expected, we
      could not demonstrate any etiology-independent link between the severity of
      hippocampal interneuron loss and the overall risk of spontaneous seizures.

PMID- 24096382
TI  - The impact of breast cancer knowledge and attitudes on screening and early
      detection among an immigrant Iranian population in southern California.
AB  - Few studies explored factors influencing breast cancer screening and early
      detection behaviors among immigrant Iranian women residing in the USA. Using a
      cross-sectional survey, a convenience sample of 319 Iranian American women was
      selected to investigate the impact of breast cancer knowledge and attitude on
      screening. A self-administered questionnaire assessed breast cancer screening
      knowledge, attitude, and mammography use (ever, previous year, and future
      intention). 79 % of the women in the study reported ever receiving at least one
      mammogram and 74 % received a mammogram in the past year. Personal attitude had
      an independent significant effect on: mammography use in the last year, ever use
      of mammography, and future intention to screen. Knowledge and morality-induced
      attitude influenced screening behavior but not significantly. Interventions
      targeting breast cancer screening among immigrant Iranian women in the USA should
      focus on enhancing personal attitudes in order to influence actual screening
      behavior. 

PMID- 24096383
TI  - Babies born dying: just bad karma? A discussion paper.
AB  - The paper examines the notion of being born dying and karma. Karma is a belief
      upheld by Buddhists and non-Buddhists: That is, karma follows people from their
      previous lives into their current lives. This raises a difficult question: Does
      karma mean that a baby's death is its own fault? While great peace can be found
      from a belief in karma, the notion of a baby's karma returning in some sort of
      retributive, universal justice can be de-emphasized and is considered "un
      Buddhist." Having an understanding of karma is intrinsic to the spiritual care
      for the dying baby, not only from the perspective of parents and families who
      have these beliefs, but also for reconciling one's own beliefs as a healthcare
      practitioner. 

PMID- 24096384
TI  - Spiritual energy of Islamic prayers as a catalyst for psychotherapy.
AB  - Islamic prayers can produce spiritual energy that may yield many psychological
      benefits, such as amelioration of stress and improvement in subjective well
      being, interpersonal sensitivity, and mastery. Islamic prayers can also be
      integrated into mainstream therapeutic interventions with religious Muslim
      clients, and this integration can mobilize, transform, and invigorate the process
      of psychotherapy. This paper provides methods that can be used for the explicit
      integration of Islamic prayers into traditional psychotherapy. Further, the paper
      offers strategies for avoiding potential pitfalls that may hamper this process.
      Finally, a case study illustrating this therapeutic integration and its
      psychological benefits will be presented. 

PMID- 24096386
TI  - Hydrogen-bond-supported dimeric boron complexes of potentially tetradentate beta
      diketiminate ligands.
AB  - Two dimeric boron complexes of potentially tetradentate and trianionic beta
      diketiminate ligands bearing phenol substituents were prepared and characterized.
      The synthetic routes employed were designed to circumvent the undesirable
      formation of beta-ketimines and 2-methylbenzoxazoles observed when traditional
      synthetic routes toward the target beta-diketiminate ligands were attempted. The
      title complexes were isolated via demethylation of beta-diketimine ligands and
      boron difluoride complexes bearing 2-anisole N-aryl substituents using boron
      tribromide. The resulting complexes were found to contain a unique hydrogen-bond
      supported boron-oxygen-boron bridge, as confirmed by X-ray crystallography. The
      stability of the resulting dimeric structures relative to the corresponding
      monomeric, tetradentate boron complexes was studied computationally, and theory
      confirmed that the dimeric structures were strongly favored. The absorption
      spectra of the dimers were red-shifted relative to the parent beta-diketimine
      ligands. The complexes were irreversibly oxidized and reduced electrochemically
      and were weakly emissive at low concentrations (Stokes shifts between 23 and 31
      nm), showing little solvent dependence. 

PMID- 24096385
TI  - The role of volunteer services at cancer centers.
AB  - Volunteer services can be effectively used to provide valuable supportive
      services to patients with cancer and their family. Providing companionship, a
      sense of self-worth, information, and respite care are among the important
      services typically provided by volunteers through outpatient, inpatient, and
      hospice services. Supportive benefits have been linked with reduced symptoms and
      may even enhance survival. Offering inpatient and outpatient respite services
      provides needed relief for family caregivers. Complementary therapies may also be
      provided through volunteer services, with research studies consistently showing
      benefits from Reiki and animal-assisted therapy offered through volunteer care. 

PMID- 24096387
TI  - A conditional predictive p-value to compare a multinomial with an overdispersed
      multinomial in the analysis of T-cell populations.
AB  - Immunological experiments that record primary molecular sequences of T-cell
      receptors produce moderate to high-dimensional categorical data, some of which
      may be subject to extra-multinomial variation caused by technical constraints of
      cell-based assays. Motivated by such experiments in melanoma research, we develop
      a statistical procedure for testing the equality of two discrete populations,
      where one population delivers multinomial data and the other is subject to a
      specific form of overdispersion. The procedure computes a conditional-predictive
      p-value by splitting the data set into two, obtaining a predictive distribution
      for one piece given the other, and using the observed predictive ordinate to
      generate a p-value. The procedure has a simple interpretation, requires fewer
      modeling assumptions than would be required of a fully Bayesian analysis, and has
      reasonable operating characteristics as evidenced empirically and by asymptotic
      analysis. 

PMID- 24096388
TI  - High-dimensional, massive sample-size Cox proportional hazards regression for
      survival analysis.
AB  - Survival analysis endures as an old, yet active research field with applications
      that spread across many domains. Continuing improvements in data acquisition
      techniques pose constant challenges in applying existing survival analysis
      methods to these emerging data sets. In this paper, we present tools for fitting
      regularized Cox survival analysis models on high-dimensional, massive sample-size
      (HDMSS) data using a variant of the cyclic coordinate descent optimization
      technique tailored for the sparsity that HDMSS data often present. Experiments on
      two real data examples demonstrate that efficient analyses of HDMSS data using
      these tools result in improved predictive performance and calibration. 

PMID- 24096389
TI  - Usefulness of Corsair microcatheter to cross stent struts in bifurcation lesions.
AB  - Side branch compromise after stenting in bifurcation lesions is a matter of
      concern. It may happen that even low-profile balloon catheters do not cross stent
      struts after rewiring. The Corsair catheter is a hybrid catheter that has
      features of a microcatheter and a support catheter. The present study evaluated
      usefulness of the Corsair catheter to facilitate advancing a low-profile balloon
      catheter through stent struts in bifurcation lesions. After rewiring, low-profile
      balloon catheters failed to cross stent struts of 29 bifurcation lesions. The
      Corsair microcatheter successfully crossed stent struts in all lesions except one
      (97 %) where a stent was implanted to treat in-stent restenosis (stent-in-stent).
      Low-profile balloon catheters were able to advance into the side branch of all
      bifurcation lesions where the Corsair microcatheter crossed stent struts. In
      conclusion, the Corsair microcatheter may be utilized if low-profile balloon
      catheters are unable to cross stent struts in bifurcation lesions. 

PMID- 24096390
TI  - An ultrafast surface-bound photo-active molecular motor.
AB  - We report the synthesis and surface attachment of an ultrafast light-driven
      rotary molecular motor. Transient absorption spectroscopy revealed that the half
      life of the rate determining thermal step of the rotary cycle in solution is 38
      +/- 1 ns, the shortest yet observed, making this the fastest molecular motor
      reported. Incorporation of acetylene legs into the structure allowed the motors
      to be grafted to azide-modified quartz and silicon substrates using the "click"
      1,3-dipolar cycloaddition reaction. 

PMID- 24096391
TI  - Remission and functioning in major depressive disorder.
AB  - Evidence from numerous clinical studies has shown that the optimal goal for the
      treatment of depression is remission. Remission implies that the signs and
      symptoms of the disease are absent or virtually absent, which is typically
      associated with a return to the patient s previous daily functioning. Functioning
      in depression is a broad concept that covers different domains. There are many
      validated instruments for its assessment, these being reviewed in this article.
      Furthermore, recovering the pre-morbid level of functioning level is increasingly
      being identified as a significant target in addition to symptomatic remission. In
      this sense, functional recovery has been associated with better prognosis of
      depression and is also a clinical goal expressed by the patient. Several factors,
      like complete remission of symptoms, with no residual symptoms, maintenance of
      remission, quality of remission, early remission, have been identified as
      contributors to functional recovery. In order to facilitate the clinical
      outcomes, evaluation of and search for symptomatic remission as well as
      functional recovery need to be integrated into the clinical practice. 

PMID- 24096392
TI  - Comorbidity between bipolar disorder and cluster B personality disorders as
      indicator of affective dysregulation and clinical severity.
AB  - INTRODUCTION: Several lines of evidence have well established a relationship
      between Bipolar Disorder and Cluster B Personality Disorders. The study compares
      mood spectrum and temperamental symptoms, personality traits and clinical
      characteristics among outpatients (n = 63) diagnosed with major depression (MD),
      bipolar disorder (BD), cluster B personality disorders (PD-B) and comorbidity of
      BD + PD-B. METHOD: The diagnosis was determined with structured interviews (MINI
      and SCID II) and symptom assessments with evaluation and diagnostic instruments
      (MOODS-SR, BI, TEMPS-A and IPDE). Differences between groups were explored with
      post hoc analysis and analysis of variance. RESULTS: Patients with BD+PD-B
      comorbidity presented an earlier onset and more severity in suicide attempts,
      hospitalizations and self-harm behaviors. They showed more characteristics of
      cyclothymic and irritable temperament and more cluster A and B personality
      traits, than patients with BD only. PD-B patients obtained intermediate scores in
      manic like symptoms: higher than patients with depression and lower than patients
      with bipolar disorder. However, the Bipolarity Index clearly distinguished
      patients with BD or with comorbidity (BD+PD-B) from the other diagnostic groups
      (PD-B and MD). CONCLUSIONS: BD+PD-B comorbidity presents a more severe type of
      emotional dysregulation compared to the other diagnostic groups, including BD and
      PD-B alone. Assessing temperament, personality traits, emotional dysregulation in
      mania and depression, self-harm and hospitalizations severity and age onset could
      facilitate differential diagnosis and enhance effectiveness of treatments for BD,
      PD-B and their comorbidity.

PMID- 24096393
TI  - Evaluation of an intensive intervention program in suicidal behaviour.
AB  - INTRODUCTION: Suicide is a public health problem. Consumed suicides reach 1
      million cases per year worldwide and it is estimated that the number of suicide
      attempts is 10 to 20 times higher. The aim of this study was to evaluate the
      effectiveness in reducing repeat suicide attempts in a program for the prevention
      of suicidal behavior: Intensive Intervention Program (IIP). METHODS: We performed
      a study that compared a cohort of patients exposed to IIP intervention with
      another cohort of patients exposed to conventional therapy. The sample was made
      up of 191 patients, 89 in the treatment group and 102 patients in conventional
      treatment group, with a 12-month follow-up. RESULTS: Relapse occurred in 20.6% of
      patients receiving conventional treatment relapse compared with 10% in the
      treatment group (p=0.047). Patients treated in the program had a 2.88 times lower
      risk of relapse (p=0.015), this being independent of the number of previous
      attempts, age, gender, need for admission after the index attempt and aggregated
      diagnosis. CONCLUSIONS: The results show that subjects who are treated in the IIP
      relapse less, need fewer admissions and the time elapsed between the treatment
      and the first repeat suicide attempt is greater.

PMID- 24096394
TI  - Adaptation into Spanish of the Clinically Useful Depression Outcome Scale (CUDOS)
      for assessing major depressive disorder from the patient's perspective.
AB  - OBJECTIVE: To adapt the CUDOS scale (Clinically Useful Depression Outcome Scale)
      into Spanish and to test its psychometrical properties in a sample of patients
      with major depressive disorder (MDD). METHODS: A two-step cross-sectional,
      multicenter validation study was conducted (linguistic adaptation into Spanish
      and psychometric validation). The study evaluated patients attended in Primary
      Care with a MDD diagnosis within the last 3 months (DSM-IV TR criteria). The
      following scales were administered: CUDOS, PRIME-MD (Primary Care Evaluation of
      Mental Disorders), HAMD-17 (Hamilton Depression Rating Scale), SOFAS (Social and
      Occupational Functioning Assessment Scale), SF-36 (Physical -PCS- and Mental -MCS
      Component Summaries), and the CGI-S & PGI-S (Clinical Global Impression for
      Severity of Illness scales for clinicians and patients, respectively).
      Feasibility, reliability, and validity of the Spanish version were assessed.
      RESULTS: In the validation study, 305 MDD patients (69.5% female) with a mean age
      (standard deviation-SD-) of 51.75(15.53) were included. Mean completion time was
      4.47(2.4) minutes. Floor or ceiling effects were found in less than 1% of the
      case scores. Internal consistency was adequate (Cronbach's alpha= 0.88). Pearson
      correlation coefficients with CUDOS were: -0.42 (SOFAS), 0.45 (HAMD-17), -0.22
      (PCS), -0.65 (MCS); all p<0.001. The CUDOS properly discriminated among clinical
      severity levels (p<0.03). CONCLUSIONS: The adapted Spanish version of the CUDOS
      shows adequate psychometric properties as an evaluation instrument of major
      depression from the patient's perspective.

PMID- 24096395
TI  - The problem of psychopathology and phenomenology. What is viable and not viable
      in phenomenological psychiatry.
AB  - The epistemological underpinnings of psychiatric theory and practice have always
      been unstable. This reflects the essential contradiction existing between the
      task (the description and individuation of speech and behavior as
      psychopathological symptoms) and tools (semiotics). As a result of this
      contradiction, the history of psychiatry is one of permanent crisis in which
      there are moments of temporary stability as approaches that aim at organizing
      this mismatch between tasks and tools gain prevalence. However, these approaches
      can only offer a false sense of unity, consistency and progress. In this sense, a
      narrow perspective on a particular period may lead us to believe that psychiatry
      is just another medical specialty with its own specific theoretical framework
      like others. However, any such perspective overlooks the coexistence of different
      schools, disagreements, contradictions, global alternatives, etc. For a certain
      period of time, phenomenology was assumed to be as the solution for
      psychiatry&#8217;s internal contradiction. As we see it, phenomenology was only
      partially understood. Despite the great influence it exerted upon psychiatry
      worldwide, it finally fell into disuse as a mere empiricism. Husserl&#8217;s
      phenomenology was more thoroughly understood and better assimilated by other
      psychiatrists, and its influence has persisted to the present day. If we view
      phenomenology in its proper (Husserlian) sense, it is possible to understand
      psychopathology as a means of creating intelligibility and clarifying the
      uniqueness of psychiatry. On the other hand, if phenomenology is understood as a
      representational theory, it will eventually lead to an unavoidable relapse into
      psychologism, which has been the main path of psychiatry until now. 

PMID- 24096396
TI  - Controversies regarding bipolar disorder in preschool age: case report.
AB  - There is some discussion concerning the phenomenology of pediatric bipolar
      disorder. This condition is marked by irritability and sudden mood swings, and
      has no specific diagnostic criteria. Disagreement is even greater for bipolar
      disorder in preschool age. We report the case of a child of four years and nine
      months with diagnosis of bipolar disorder not otherwise specified. Predominant
      symptom presents as irritability with outbursts of anger, verbal aggression and
      strange and grandiose utterances, all of them with a very fluctuating temporal
      pattern. We found similar cases and discrepancies in previous publications. It
      has been suggested that patients with non-episodic irritability may receive a
      diagnosis of severe mood dysregulation disorder. Further studies on mood
      disorders in preschool children are required.

PMID- 24096397
TI  - Recurrence of neuroleptic malignant syndrome.
AB  - Neuroleptic malignant syndrome (NMS) is a rare idiosyncratic reaction associated
      with the use of neuroleptics that has an incidence of 0.02 to 3% among patients
      taking these drugs. This is a very serious complication with a mortality rate
      that reaches 10-20%. It is therefore very important to have high clinical
      suspicion and use appropriate criteria to objectify this clinical picture early,
      stopping the medication causing the picture and to avoid the subsequent
      complications as much as possible that would be responsible for both its
      mortality and sequels. We present that case of an 81-year old woman who was
      admitted to the Psychiatric Hospitalization Unit (PHU) for a depressive episode
      with psychotic symptoms who developed a neuroleptic malignant syndrome (NMS) when
      Haloperidol was introduced. After its suspension and subsequent clinical
      recovery, antipsychotic treatment with Risperidone was reintroduced and she
      suffered a recurrence of NMS. Finally, significant improvement was achieved with
      several sessions of electroshock therapy (EST).

PMID- 24096398
TI  - Zooming in on eukaryotic translation initiation.
AB  - Translation initiation in eukaryotes is a complex and highly regulated process
      during which several initiation factors cooperate to recruit an initiator tRNA to
      the small ribosomal subunit, where the mRNA is scanned for an AUG start codon.
      Two recent reports provide new structural insights into this process and reveal
      key functions of initiation factors 1 (eIF1) and 1A (eIF1A) in start-codon
      selection in atomic detail.

PMID- 24096399
TI  - Substrate-induced rearrangements in glutamate-transporter homologs.
AB  - Sodium-coupled glutamate transporters regulate excitatory signaling in the brain.
      A new crystal structure shows how the substrate induces changes in the binding
      pocket of an archaeal transporter homolog, providing new insights into the
      mechanism of transport.

PMID- 24096400
TI  - An express elevator for Na+/H+.

PMID- 24096404
TI  - Tony Pawson 1952-2013.

PMID- 24096410
TI  - Gloveport hernioscopy.
AB  - It can be difficult to exclude occult, necrotic bowel in incarcerated herniae
      that reduce prior to emergent surgical exploration without resorting to further
      abdominal wall incisions. This case illustrates the Gloveport hernioscopy
      technique to identify necrotic small intestine that had spontaneously reduced in
      a man with a strangulated umbilical hernia. This minimally invasive technique
      allowed a multichannel examination of the peritoneal cavity without any further
      insult to the abdominal wall.

PMID- 24096405
TI  - Transcriptional regulation by Polycomb group proteins.
AB  - Polycomb group (PcG) proteins are epigenetic regulators of transcription that
      have key roles in stem-cell identity, differentiation and disease.
      Mechanistically, they function within multiprotein complexes, called Polycomb
      repressive complexes (PRCs), which modify histones (and other proteins) and
      silence target genes. The dynamics of PRC1 and PRC2 components has been the focus
      of recent research. Here we discuss our current knowledge of the PRC complexes,
      how they are targeted to chromatin and how the high diversity of the PcG proteins
      allows these complexes to influence cell identity. 

PMID- 24096411
TI  - Discordant cardiac xenotransplantation: broadening the horizons.

PMID- 24096412
TI  - Flow sorting and sequencing meadow fescue chromosome 4F.
AB  - The analysis of large genomes is hampered by a high proportion of repetitive DNA,
      which makes the assembly of short sequence reads difficult. This is also the case
      in meadow fescue (Festuca pratensis), which is known for good abiotic stress
      resistance and has been used in intergeneric hybridization with ryegrasses
      (Lolium spp.) to produce Festulolium cultivars. In this work, we describe a new
      approach to analyze the large genome of meadow fescue, which involves the
      reduction of sample complexity without compromising information content. This is
      achieved by dissecting the genome to smaller parts: individual chromosomes and
      groups of chromosomes. As the first step, we flow sorted chromosome 4F and
      sequenced it by Illumina with approximately 50* coverage. This provided, to our
      knowledge, the first insight into the composition of the fescue genome, enabled
      the construction of the virtual gene order of the chromosome, and facilitated
      detailed comparative analysis with the sequenced genomes of rice (Oryza sativa),
      Brachypodium distachyon, sorghum (Sorghum bicolor), and barley (Hordeum vulgare).
      Using GenomeZipper, we were able to confirm the collinearity of chromosome 4F
      with barley chromosome 4H and the long arm of chromosome 5H. Several new tandem
      repeats were identified and physically mapped using fluorescence in situ
      hybridization. They were found as robust cytogenetic markers for karyotyping of
      meadow fescue and ryegrass species and their hybrids. The ability to purify
      chromosome 4F opens the way for more efficient analysis of genomic loci on this
      chromosome underlying important traits, including freezing tolerance. Our results
      confirm that next-generation sequencing of flow-sorted chromosomes enables an
      overview of chromosome structure and evolution at a resolution never achieved
      before. 

PMID- 24096413
TI  - Abundant type III lipid transfer proteins in Arabidopsis tapetum are secreted to
      the locule and become a constituent of the pollen exine.
AB  - Lipid transfer proteins (LTPs) are small secretory proteins in plants with
      defined lipid-binding structures for possible lipid exocytosis. Special groups of
      LTPs unique to the anther tapetum are abundant, but their functions are unclear.
      We studied a special group of LTPs, type III LTPs, in Arabidopsis (Arabidopsis
      thaliana). Their transcripts were restricted to the anther tapetum, with levels
      peaking at the developmental stage of maximal pollen-wall exine synthesis. We
      constructed an LTP-Green Fluorescent Protein (LTP-GFP) plasmid, transformed it
      into wild-type plants, and monitored LTP-GFP in developing anthers with confocal
      laser scanning microscopy. LTP-GFP appeared in the tapetum and was secreted via
      the endoplasmic reticulum-trans-Golgi network machinery into the locule. It then
      moved to the microspore surface and remained as a component of exine. Immuno
      transmission electron microscopy of native LTP in anthers confirmed the LTP-GFP
      observations. The in vivo association of LTP-GFP and exine in anthers was not
      observed with non-type III or structurally modified type III LTPs or in
      transformed exine-defective mutant plants. RNA interference knockdown of
      individual type III LTPs produced no observable mutant phenotypes. RNA
      interference knockdown of two type III LTPs produced microscopy-observable
      morphologic changes in the intine underneath the exine (presumably as a
      consequence of changes in the exine not observed by transmission electron
      microscopy) and pollen susceptible to dehydration damage. Overall, we reveal a
      novel transfer pathway of LTPs in which LTPs bound or nonbound to exine
      precursors are secreted from the tapetum to become microspore exine constituents;
      this pathway explains the need for plentiful LTPs to incorporate into the
      abundant exine. 

PMID- 24096414
TI  - Oxidation of the cyclic ethers 1,4-dioxane and tetrahydrofuran by a monooxygenase
      in two Pseudonocardia species.
AB  - The bacterium Pseudonocardia dioxanivorans CB1190 grows on the cyclic ethers 1,4
      dioxane (dioxane) and tetrahydrofuran (THF) as sole carbon and energy sources.
      Prior transcriptional studies indicated that an annotated THF monooxygenase (THF
      MO) gene cluster, thmADBC, located on a plasmid in CB1190 is upregulated during
      growth on dioxane. In this work, transcriptional analysis demonstrates that
      upregulation of thmADBC occurs during growth on the dioxane metabolite beta
      hydroxyethoxyacetic acid (HEAA) and on THF. Comparison of the transcriptomes of
      CB1190 grown on THF and succinate (an intermediate of THF degradation) permitted
      the identification of other genes involved in THF metabolism. Dioxane and THF
      oxidation activity of the THF MO was verified in Rhodococcus jostii RHA1 cells
      heterologously expressing the CB1190 thmADBC gene cluster. Interestingly, these
      thmADBC expression clones accumulated HEAA as a dead-end product of dioxane
      transformation, indicating that despite its genes being transcriptionally
      upregulated during growth on HEAA, the THF MO enzyme is not responsible for
      degradation of HEAA in CB1190. Similar activities were also observed in RHA1
      cells heterologously expressing the thmADBC gene cluster from Pseudonocardia
      tetrahydrofuranoxydans K1. 

PMID- 24096415
TI  - GET_HOMOLOGUES, a versatile software package for scalable and robust microbial
      pangenome analysis.
AB  - GET_HOMOLOGUES is an open-source software package that builds on popular
      orthology-calling approaches making highly customizable and detailed pangenome
      analyses of microorganisms accessible to nonbioinformaticians. It can cluster
      homologous gene families using the bidirectional best-hit, COGtriangles, or
      OrthoMCL clustering algorithms. Clustering stringency can be adjusted by scanning
      the domain composition of proteins using the HMMER3 package, by imposing desired
      pairwise alignment coverage cutoffs, or by selecting only syntenic genes. The
      resulting homologous gene families can be made even more robust by computing
      consensus clusters from those generated by any combination of the clustering
      algorithms and filtering criteria. Auxiliary scripts make the construction,
      interrogation, and graphical display of core genome and pangenome sets easy to
      perform. Exponential and binomial mixture models can be fitted to the data to
      estimate theoretical core genome and pangenome sizes, and high-quality graphics
      can be generated. Furthermore, pangenome trees can be easily computed and basic
      comparative genomics performed to identify lineage-specific genes or gene family
      expansions. The software is designed to take advantage of modern multiprocessor
      personal computers as well as computer clusters to parallelize time-consuming
      tasks. To demonstrate some of these capabilities, we survey a set of 50
      Streptococcus genomes annotated in the Orthologous Matrix (OMA) browser as a
      benchmark case. The package can be downloaded at
      http://www.eead.csic.es/compbio/soft/gethoms.php and
      http://maya.ccg.unam.mx/soft/gethoms.php. 

PMID- 24096416
TI  - Isolation and characterization of Burkholderia rinojensis sp. nov., a non
      Burkholderia cepacia complex soil bacterium with insecticidal and miticidal
      activities.
AB  - Isolate A396, a bacterium isolated from a Japanese soil sample demonstrated
      strong insecticidal and miticidal activities in laboratory bioassays. The isolate
      was characterized through biochemical methods, fatty acid methyl ester (FAME)
      analysis, sequencing of 16S rRNA, multilocus sequence typing and analysis, and
      DNA-DNA hybridization. FAME analysis matched A396 to Burkholderia cenocepacia,
      but this result was not confirmed by 16S rRNA or DNA-DNA hybridization. 16S rRNA
      sequencing indicated closest matches with B. glumae and B. plantarii. DNA-DNA
      hybridization experiments with B. plantarii, B. glumae, B. multivorans, and B.
      cenocepacia confirmed the low genetic similarity (11.5 to 37.4%) with known
      members of the genus. PCR-based screening showed that A396 lacks markers
      associated with members of the B. cepacia complex. Bioassay results indicated two
      mechanisms of action: through ingestion and contact. The isolate effectively
      controlled beet armyworms (Spodoptera exigua; BAW) and two-spotted spider mites
      (Tetranychus urticae; TSSM). In diet overlay bioassays with BAW, 1% to 4%
      (vol/vol) dilution of the whole-cell broth caused 97% to 100% mortality 4 days
      postexposure, and leaf disc treatment bioassays attained 75% +/- 22% mortality 3
      days postexposure. Contact bioassays led to 50% larval mortality, as well as
      discoloration, stunting, and failure to molt. TSSM mortality reached 93% in
      treated leaf discs. Activity was maintained in cell-free supernatants and after
      heat treatment (60 degrees C for 2 h), indicating that a secondary metabolite or
      excreted thermostable enzyme might be responsible for the activity. Based on
      these results, we describe the novel species Burkholderia rinojensis, a good
      candidate for the development of a biocontrol product against insect and mite
      pests. 

PMID- 24096418
TI  - Prevalence of nonpolio enteroviruses in the sewage of Guangzhou city, China, from
      2009 to 2012.
AB  - The human-pathogenic viruses in urban sewage have been extensively monitored to
      obtain information on circulating viruses in human communities. Enteroviruses
      (EVs) excreted by patients who present with diverse clinical syndromes can remain
      infectious in the environment for several weeks, and limited data on circulating
      environmental EVs are available. A 4-year (2009 to 2012) surveillance study was
      conducted to detect nonpolio enteroviruses (NPEVs) in the urban sewage of
      Guangzhou city, China. After the viruses in the sewage samples were concentrated
      and isolated, molecular identification was used to detect and type the NPEVs.
      During the 4-year study, 17 different NPEV serotypes were identified in the
      sewage of Guangzhou city. The most common serotypes were echovirus 11 (ECHO11),
      ECHO6, ECHO7, and ECHO12 and coxsackie group B viruses 5 (CVB5) and CVB3. The
      predominant serotypes were influenced by spatial and temporal factors and
      differed each year. CVB5 was commonly detected in 2009 and 2010 but was rarely
      isolated in 2011 and 2012. In contrast, CVB3 was not observed in 2009 and 2010
      but was increasingly detected in 2011 and 2012. Our study provides an overview of
      the serotype distribution and circulation patterns of NPEVs in the sewage of
      Guangzhou, China. In the absence of a systematic EV disease surveillance system,
      the detection and characterization of sewage-borne NPEVs will help us better
      understand the changes in EV disease trends and the epidemic background of
      circulating EVs, which could help interpret the EV trends and warn of future
      outbreaks in this area. 

PMID- 24096417
TI  - Diverse broad-host-range plasmids from freshwater carry few accessory genes.
AB  - Broad-host-range self-transferable plasmids are known to facilitate bacterial
      adaptation by spreading genes between phylogenetically distinct hosts. These
      plasmids typically have a conserved backbone region and a variable accessory
      region that encodes host-beneficial traits. We do not know, however, how well
      plasmids that do not encode accessory functions can survive in nature. The goal
      of this study was to characterize the backbone and accessory gene content of
      plasmids that were captured from freshwater sources without selecting for a
      particular phenotype or cultivating their host. To do this, triparental matings
      were used such that the only required phenotype was the plasmid's ability to
      mobilize a nonconjugative plasmid. Based on complete genome sequences of 10
      plasmids, only 5 carried identifiable accessory gene regions, and none carried
      antibiotic resistance genes. The plasmids belong to four known incompatibility
      groups (IncN, IncP-1, IncU, and IncW) and two potentially new groups. Eight of
      the plasmids were shown to have a broad host range, being able to transfer into
      alpha-, beta-, and gammaproteobacteria. Because of the absence of antibiotic
      resistance genes, we resampled one of the sites and compared the proportion of
      captured plasmids that conferred antibiotic resistance to their hosts with the
      proportion of such plasmids captured from the effluent of a local wastewater
      treatment plant. Few of the captured plasmids from either site encoded antibiotic
      resistance. A high diversity of plasmids that encode no or unknown accessory
      functions is thus readily found in freshwater habitats. The question remains how
      the plasmids persist in these microbial communities. 

PMID- 24096419
TI  - A Chrysodeixis chalcites single-nucleocapsid nucleopolyhedrovirus population from
      the Canary Islands is genotypically structured to maximize survival.
AB  - A Chrysodeixis chalcites single-nucleocapsid nucleopolyhedrovirus wild-type
      isolate from the Canary Islands, Spain, named ChchSNPV-TF1 (ChchTF1-wt), appears
      to have great potential as the basis for a biological insecticide for control of
      the pest. An improved understanding of the genotypic structure of this wild-type
      strain population should facilitate the selection of genotypes for inclusion in a
      bioinsecticidal product. Eight genetically distinct genotypes were cloned in
      vitro: ChchTF1-A to ChchTF1-H. Quantitative real-time PCR (qPCR) analysis
      confirmed that ChchTF1-A accounted for 36% of the genotypes in the wild-type
      population. In bioassays, ChchTF1-wt occlusion bodies (OBs) were significantly
      more pathogenic than any of the component single-genotype OBs, indicating that
      genotype interactions were likely responsible for the pathogenicity phenotype of
      wild-type OBs. However, the wild-type population was slower killing and produced
      higher OB yields than any of the single genotypes alone. These results strongly
      suggested that the ChchTF1-wt population is structured to maximize its
      transmission efficiency. Experimental OB mixtures and cooccluded genotype
      mixtures containing the most abundant and the rarest genotypes, at frequencies
      similar to those at which they were isolated, revealed a mutualistic interaction
      that restored the pathogenicity of OBs. In OB and cooccluded mixtures containing
      only the most abundant genotypes, ChchTF1-ABC, OB pathogenicity was even greater
      than that of wild-type OBs. The ChchTF1-ABC cooccluded mixture killed larvae 33 h
      faster than the wild-type population and remained genotypically and biologically
      stable throughout five successive passages in vivo. In conclusion, the ChchTF1
      ABC mixture shows great potential as the active ingredient of a bioinsecticide to
      control C. chalcites in the Canary Islands. 

PMID- 24096420
TI  - Two histone deacetylases, FfHda1 and FfHda2, are important for Fusarium fujikuroi
      secondary metabolism and virulence.
AB  - Histone modifications are crucial for the regulation of secondary metabolism in
      various filamentous fungi. Here we studied the involvement of histone
      deacetylases (HDACs) in secondary metabolism in the phytopathogenic fungus
      Fusarium fujikuroi, a known producer of several secondary metabolites, including
      phytohormones, pigments, and mycotoxins. Deletion of three Zn(2+)-dependent HDAC
      encoding genes, ffhda1, ffhda2, and ffhda4, indicated that FfHda1 and FfHda2
      regulate secondary metabolism, whereas FfHda4 is involved in developmental
      processes but is dispensable for secondary-metabolite production in F. fujikuroi.
      Single deletions of ffhda1 and ffhda2 resulted not only in an increase or
      decrease but also in derepression of metabolite biosynthesis under normally
      repressing conditions. Moreover, double deletion of both the ffhda1 and ffhda2
      genes showed additive but also distinct phenotypes with regard to secondary
      metabolite biosynthesis, and both genes are required for gibberellic acid (GA)
      induced bakanae disease on the preferred host plant rice, as Deltaffhda1
      Deltaffhda2 mutants resemble the uninfected control plant. Microarray analysis
      with a Deltaffhda1 mutant that has lost the major HDAC revealed differential
      expression of secondary-metabolite gene clusters, which was subsequently verified
      by a combination of chemical and biological approaches. These results indicate
      that HDACs are involved not only in gene silencing but also in the activation of
      some genes. Chromatin immunoprecipitation with the Deltaffhda1 mutant revealed
      significant alterations in the acetylation state of secondary-metabolite gene
      clusters compared to the wild type, thereby providing insights into the
      regulatory mechanism at the chromatin level. Altogether, manipulation of HDAC
      encoding genes constitutes a powerful tool to control secondary metabolism in
      filamentous fungi. 

PMID- 24096421
TI  - Sequence-based analysis of the intestinal Microbiota of sows and their offspring
      fed genetically modified maize expressing a truncated form of Bacillus
      thuringiensis Cry1Ab protein (Bt Maize).
AB  - The aim was to investigate transgenerational effects of feeding genetically
      modified (GM) maize expressing a truncated form of Bacillus thuringiensis Cry1Ab
      protein (Bt maize) to sows and their offspring on maternal and offspring
      intestinal microbiota. Sows were assigned to either non-GM or GM maize dietary
      treatments during gestation and lactation. At weaning, offspring were assigned
      within sow treatment to non-GM or GM maize diets for 115 days, as follows: (i)
      non-GM maize-fed sow/non-GM maize-fed offspring (non-GM/non-GM), (ii) non-GM
      maize-fed sow/GM maize-fed offspring (non-GM/GM), (iii) GM maize-fed sow/non-GM
      maize-fed offspring (GM/non-GM), and (iv) GM maize-fed sow/GM maize-fed offspring
      (GM/GM). Offspring of GM maize-fed sows had higher counts of fecal total
      anaerobes and Enterobacteriaceae at days 70 and 100 postweaning, respectively. At
      day 115 postweaning, GM/non-GM offspring had lower ileal Enterobacteriaceae
      counts than non-GM/non-GM or GM/GM offspring and lower ileal total anaerobes than
      pigs on the other treatments. GM maize-fed offspring also had higher ileal total
      anaerobe counts than non-GM maize-fed offspring, and cecal total anaerobes were
      lower in non-GM/GM and GM/non-GM offspring than in those from the non-GM/non-GM
      treatment. The only differences observed for major bacterial phyla using 16S rRNA
      gene sequencing were that fecal Proteobacteria were less abundant in GM maize-fed
      sows prior to farrowing and in offspring at weaning, with fecal Firmicutes more
      abundant in offspring. While other differences occurred, they were not observed
      consistently in offspring, were mostly encountered for low-abundance, low
      frequency bacterial taxa, and were not associated with pathology. Therefore,
      their biological relevance is questionable. This confirms the lack of adverse
      effects of GM maize on the intestinal microbiota of pigs, even following
      transgenerational consumption. 

PMID- 24096422
TI  - Differential induction of antimicrobial REGIII by the intestinal microbiota and
      Bifidobacterium breve NCC2950.
AB  - The intestinal microbiota is a key determinant of gut homeostasis, which is
      achieved, in part, through regulation of antimicrobial peptide secretion. The aim
      of this study was to determine the efficiency by which members of the intestinal
      microbiota induce the antimicrobial peptide REGIII and to elucidate the
      underlying pathways. We showed that germfree mice have low levels of REGIII-gamma
      in their ileum and colon compared to mice with different intestinal microbiota
      backgrounds. Colonization with a microbiota of low diversity (altered Schaedler
      flora) did not induce the expression of REGIII-gamma as effectively as a complex
      community (specific pathogen free). Monocolonization with the probiotic
      Bifidobacterium breve, but not with the nonprobiotic commensal Escherichia coli
      JM83, upregulated REGIII-gamma expression. Induction of REGIII-gamma by B. breve
      was abrogated in mice lacking MyD88 and Ticam1 signaling. Both live and heat
      inactivated B. breve but not spent culture medium from B. breve induced the
      expression of REGIII-alpha, the human ortholog and homolog of REGIII-gamma, in
      human colonic epithelial cells (Caco-2). Taken together, the results suggest that
      REGIII-gamma expression in the intestine correlates with the richness of
      microbiota composition. Also, specific bacteria such as Bifidobacterium breve
      NCC2950 effectively induce REGIII production in the intestine via the MyD88
      Ticam1 pathway. Treatment with this probiotic may enhance the mucosal barrier and
      protect the host from infection and inflammation. 

PMID- 24096423
TI  - Meta-analysis of quantification methods shows that archaea and bacteria have
      similar abundances in the subseafloor.
AB  - There is no universally accepted method to quantify bacteria and archaea in
      seawater and marine sediments, and different methods have produced conflicting
      results with the same samples. To identify best practices, we compiled data from
      65 studies, plus our own measurements, in which bacteria and archaea were
      quantified with fluorescent in situ hybridization (FISH), catalyzed reporter
      deposition FISH (CARD-FISH), polyribonucleotide FISH, or quantitative PCR (qPCR).
      To estimate efficiency, we defined "yield" to be the sum of bacteria and archaea
      counted by these techniques divided by the total number of cells. In seawater,
      the yield was high (median, 71%) and was similar for FISH, CARD-FISH, and
      polyribonucleotide FISH. In sediments, only measurements by CARD-FISH in which
      archaeal cells were permeabilized with proteinase K showed high yields (median,
      84%). Therefore, the majority of cells in both environments appear to be alive,
      since they contain intact ribosomes. In sediments, the sum of bacterial and
      archaeal 16S rRNA gene qPCR counts was not closely related to cell counts, even
      after accounting for variations in copy numbers per genome. However, qPCR
      measurements were precise relative to other qPCR measurements made on the same
      samples. qPCR is therefore a reliable relative quantification method.
      Inconsistent results for the relative abundance of bacteria versus archaea in
      deep subsurface sediments were resolved by the removal of CARD-FISH measurements
      in which lysozyme was used to permeabilize archaeal cells and qPCR measurements
      which used ARCH516 as an archaeal primer or TaqMan probe. Data from best-practice
      methods showed that archaea and bacteria decreased as the depth in seawater and
      marine sediments increased, although archaea decreased more slowly. 

PMID- 24096424
TI  - Lysozyme and penicillin inhibit the growth of anaerobic ammonium-oxidizing
      planctomycetes.
AB  - Anaerobic ammonium-oxidizing (anammox) planctomycetes oxidize ammonium in the
      absence of molecular oxygen with nitrite as the electron acceptor. Although
      planctomycetes are generally assumed to lack peptidoglycan in their cell walls,
      recent genome data imply that the anammox bacteria have the genes necessary to
      synthesize peptidoglycan-like cell wall structures. In this study, we
      investigated the effects of two antibacterial agents that target the integrity
      and synthesis of peptidoglycan (lysozyme and penicillin G) on the anammox
      bacterium Kuenenia stuttgartiensis. The effects of these compounds were
      determined in both short-term batch incubations and long-term (continuous
      cultivation) growth experiments in membrane bioreactors. Lysozyme at 1 g/liter
      (20 mM EDTA) lysed anammox cells in less than 60 min, whereas penicillin G did
      not have any observable short-term effects on anammox activity. Penicillin G
      (0.5, 1, and 5 g/liter) reversibly inhibited the growth of anammox bacteria in
      continuous-culture experiments. Furthermore, transcriptome analyses of the
      penicillin G-treated reactor and the control reactor revealed that penicillin G
      treatment resulted in a 10-fold decrease in the ribosome levels of the cells. One
      of the cell division proteins (Kustd1438) was downregulated 25-fold. Our results
      suggested that anammox bacteria contain peptidoglycan-like components in their
      cell wall that can be targeted by lysozyme and penicillin G-sensitive proteins
      were involved in their synthesis. Finally, we showed that a continuous membrane
      reactor system with free-living planktonic cells was a very powerful tool to
      study the physiology of slow-growing microorganisms under physiological
      conditions. 

PMID- 24096425
TI  - Induction of the Cpx envelope stress pathway contributes to Escherichia coli
      tolerance to antimicrobial peptides.
AB  - Antimicrobial peptides produced by multicellular organisms as part of their
      innate system of defense against microorganisms are currently considered
      potential alternatives to conventional antibiotics in case of infection by
      multiresistant bacteria. However, while the mode of action of antimicrobial
      peptides is relatively well described, resistance mechanisms potentially induced
      or selected by these peptides are still poorly understood. In this work, we
      studied the mechanisms of action and resistance potentially induced by ApoEdpL-W,
      a new antimicrobial peptide derived from human apolipoprotein E. Investigation of
      the genetic response of Escherichia coli upon exposure to sublethal
      concentrations of ApoEdpL-W revealed that this antimicrobial peptide triggers
      activation of RcsCDB, CpxAR, and sigma(E) envelope stress pathways. This genetic
      response is not restricted to ApoEdpL-W, since several other antimicrobial
      peptides, including polymyxin B, melittin, LL-37, and modified S4 dermaseptin,
      also activate several E. coli envelope stress pathways. Finally, we demonstrate
      that induction of the CpxAR two-component system directly contributes to E. coli
      tolerance toward ApoEdpL-W, polymyxin B, and melittin. These results therefore
      show that E. coli senses and responds to different antimicrobial peptides by
      activation of the CpxAR pathway. While this study further extends the
      understanding of the array of peptide-induced stress signaling systems, it also
      provides insight into the contribution of Cpx envelope stress pathway to E. coli
      tolerance to antimicrobial peptides. 

PMID- 24096426
TI  - Release of free DNA by membrane-impaired bacterial aerosols due to aerosolization
      and air sampling.
AB  - We report here that stress experienced by bacteria due to aerosolization and air
      sampling can result in severe membrane impairment, leading to the release of DNA
      as free molecules. Escherichia coli and Bacillus atrophaeus bacteria were
      aerosolized and then either collected directly into liquid or collected using
      other collection media and then transferred into liquid. The amount of DNA
      released was quantified as the cell membrane damage index (ID), i.e., the number
      of 16S rRNA gene copies in the supernatant liquid relative to the total number in
      the bioaerosol sample. During aerosolization by a Collison nebulizer, the ID of
      E. coli and B. atrophaeus in the nebulizer suspension gradually increased during
      60 min of continuous aerosolization. We found that the ID of bacteria during
      aerosolization was statistically significantly affected by the material of the
      Collison jar (glass > polycarbonate; P < 0.001) and by the bacterial species (E.
      coli > B. atrophaeus; P < 0.001). When E. coli was collected for 5 min by
      filtration, impaction, and impingement, its ID values were within the following
      ranges: 0.051 to 0.085, 0.16 to 0.37, and 0.068 to 0.23, respectively; when it
      was collected by electrostatic precipitation, the ID values (0.011 to 0.034) were
      significantly lower (P < 0.05) than those with other sampling methods. Air
      samples collected inside an equine facility for 2 h by filtration and impingement
      exhibited ID values in the range of 0.30 to 0.54. The data indicate that the
      amount of cell damage during bioaerosol sampling and the resulting release of DNA
      can be substantial and that this should be taken into account when analyzing
      bioaerosol samples. 

PMID- 24096427
TI  - Microbial ecology dynamics during rye and wheat sourdough preparation.
AB  - The bacterial ecology during rye and wheat sourdough preparation was described by
      16S rRNA gene pyrosequencing. Viable plate counts of presumptive lactic acid
      bacteria, the ratio between lactic acid bacteria and yeasts, the rate of
      acidification, a permutation analysis based on biochemical and microbial
      features, the number of operational taxonomic units (OTUs), and diversity indices
      all together demonstrated the maturity of the sourdoughs during 5 to 7 days of
      propagation. Flours were mainly contaminated by metabolically active genera
      (Acinetobacter, Pantoea, Pseudomonas, Comamonas, Enterobacter, Erwinia, and
      Sphingomonas) belonging to the phylum Proteobacteria or Bacteroidetes (genus
      Chryseobacterium). Their relative abundances varied with the flour. Soon after 1
      day of propagation, this population was almost completely inhibited except for
      the Enterobacteriaceae. Although members of the phylum Firmicutes were present at
      very low or intermediate relative abundances in the flours, they became dominant
      soon after 1 day of propagation. Lactic acid bacteria were almost exclusively
      representative of the Firmicutes by this time. Weissella spp. were already
      dominant in rye flour and stably persisted, though they were later flanked by the
      Lactobacillus sakei group. There was a succession of species during 10 days of
      propagation of wheat sourdoughs. The fluctuation between dominating and
      subdominating populations of L. sakei group, Leuconostoc spp., Weissella spp.,
      and Lactococcus lactis was demonstrated. Other subdominant species such as
      Lactobacillus plantarum were detectable throughout propagation. As shown by PCR
      denaturing gradient gel electrophoresis (PCR-DGGE) analysis, Saccharomyces
      cerevisiae dominated throughout the sourdough propagation. Notwithstanding
      variations due to environmental and technology determinants, the results of this
      study represent a clear example of how the microbial ecology evolves during
      sourdough preparation. 

PMID- 24096428
TI  - Regulation of dual glycolytic pathways for fructose metabolism in
      heterofermentative Lactobacillus panis PM1.
AB  - Lactobacillus panis PM1 belongs to the group III heterofermentative lactobacilli
      that use the 6-phosphogluconate/phosphoketolase (6-PG/PK) pathway as their
      central metabolic pathway and are reportedly unable to grow on fructose as a sole
      carbon source. We isolated a variant PM1 strain capable of sporadic growth on
      fructose medium and observed its distinctive characteristics of fructose
      metabolism. The end product pattern was different from what is expected in
      typical group III lactobacilli using the 6-PG/PK pathway (i.e., more lactate,
      less acetate, and no mannitol). In addition, in silico analysis revealed the
      presence of genes encoding most of critical enzymes in the Embden-Meyerhof (EM)
      pathway. These observations indicated that fructose was metabolized via two
      pathways. Fructose metabolism in the PM1 strain was influenced by the activities
      of two enzymes, triosephosphate isomerase (TPI) and glucose 6-phosphate isomerase
      (PGI). A lack of TPI resulted in the intracellular accumulation of
      dihydroxyacetone phosphate (DHAP) in PM1, the toxicity of which caused early
      growth cessation during fructose fermentation. The activity of PGI was enhanced
      by the presence of glyceraldehyde 3-phosphate (GAP), which allowed additional
      fructose to enter into the 6-PG/PK pathway to avoid toxicity by DHAP. Exogenous
      TPI gene expression shifted fructose metabolism from heterolactic to homolactic
      fermentation, indicating that TPI enabled the PM1 strain to mainly use the EM
      pathway for fructose fermentation. These findings clearly demonstrate that the
      balance in the accumulation of GAP and DHAP determines the fate of fructose
      metabolism and the activity of TPI plays a critical role during fructose
      fermentation via the EM pathway in L. panis PM1. 

PMID- 24096429
TI  - Analysis of magnetosome chains in magnetotactic bacteria by magnetic measurements
      and automated image analysis of electron micrographs.
AB  - Magnetotactic bacteria (MTB) align along the Earth's magnetic field by the
      activity of intracellular magnetosomes, which are membrane-enveloped magnetite or
      greigite particles that are assembled into well-ordered chains. Formation of
      magnetosome chains was found to be controlled by a set of specific proteins in
      Magnetospirillum gryphiswaldense and other MTB. However, the contribution of
      abiotic factors on magnetosome chain assembly has not been fully explored. Here,
      we first analyzed the effect of growth conditions on magnetosome chain formation
      in M. gryphiswaldense by electron microscopy. Whereas higher temperatures (30 to
      35 degrees C) and high oxygen concentrations caused increasingly disordered
      chains and smaller magnetite crystals, growth at 20 degrees C and anoxic
      conditions resulted in long chains with mature cuboctahedron-shaped crystals. In
      order to analyze the magnetosome chain in electron microscopy data sets in a more
      quantitative and unbiased manner, we developed a computerized image analysis
      algorithm. The collected data comprised the cell dimensions and particle size and
      number as well as the intracellular position and extension of the magnetosome
      chain. The chain analysis program (CHAP) was used to evaluate the effects of the
      genetic and growth conditions on magnetosome chain formation. This was compared
      and correlated to data obtained from bulk magnetic measurements of wild-type (WT)
      and mutant cells displaying different chain configurations. These techniques were
      used to differentiate mutants due to magnetosome chain defects on a bulk scale. 

PMID- 24096430
TI  - Anaerobic benzene oxidation via phenol in Geobacter metallireducens.
AB  - Anaerobic activation of benzene is expected to represent a novel biochemistry of
      environmental significance. Therefore, benzene metabolism was investigated in
      Geobacter metallireducens, the only genetically tractable organism known to
      anaerobically degrade benzene. Trace amounts (<0.5 MUM) of phenol accumulated in
      cultures of Geobacter metallireducens anaerobically oxidizing benzene to carbon
      dioxide with the reduction of Fe(III). Phenol was not detected in cell-free
      controls or in Fe(II)- and benzene-containing cultures of Geobacter
      sulfurreducens, a Geobacter species that cannot metabolize benzene. The phenol
      produced in G. metallireducens cultures was labeled with (18)O during growth in
      H2(18)O, as expected for anaerobic conversion of benzene to phenol. Analysis of
      whole-genome gene expression patterns indicated that genes for phenol metabolism
      were upregulated during growth on benzene but that genes for benzoate or toluene
      metabolism were not, further suggesting that phenol was an intermediate in
      benzene metabolism. Deletion of the genes for PpsA or PpcB, subunits of two
      enzymes specifically required for the metabolism of phenol, removed the capacity
      for benzene metabolism. These results demonstrate that benzene hydroxylation to
      phenol is an alternative to carboxylation for anaerobic benzene activation and
      suggest that this may be an important metabolic route for benzene removal in
      petroleum-contaminated groundwaters, in which Geobacter species are considered to
      play an important role in anaerobic benzene degradation. 

PMID- 24096431
TI  - Exploring the mechanism of biocatalyst inhibition in microbial desulfurization.
AB  - Microbial desulfurization, or biodesulfurization (BDS), of fuels is a promising
      technology because it can desulfurize compounds that are recalcitrant to the
      current standard technology in the oil industry. One of the obstacles to the
      commercialization of BDS is the reduction in biocatalyst activity concomitant
      with the accumulation of the end product, 2-hydroxybiphenyl (HBP), during the
      process. BDS experiments were performed by incubating Rhodococcus erythropolis
      IGTS8 resting-cell suspensions with hexadecane at 0.50 (vol/vol) containing 10 mM
      dibenzothiophene. The resin Dowex Optipore SD-2 was added to the BDS experiments
      at resin concentrations of 0, 10, or 50 g resin/liter total volume. The HBP
      concentration within the cytoplasm was estimated to decrease from 1,100 to 260
      MUM with increasing resin concentration. Despite this finding, productivity did
      not increase with the resin concentration. This led us to focus on the
      susceptibility of the desulfurization enzymes toward HBP. Dose-response
      experiments were performed to identify major inhibitory interactions in the most
      common BDS pathway, the 4S pathway. HBP was responsible for three of the four
      major inhibitory interactions identified. The concentrations of HBP that led to a
      50% reduction in the enzymes' activities (IC50s) for DszA, DszB, and DszC were
      measured to be 60 +/- 5 MUM, 110 +/- 10 MUM, and 50 +/- 5 MUM, respectively. The
      fact that the IC50s for HBP are all significantly lower than the cytoplasmic HBP
      concentration suggests that the inhibition of the desulfurization enzymes by HBP
      is responsible for the observed reduction in biocatalyst activity concomitant
      with HBP generation. 

PMID- 24096432
TI  - Do robotic prostatectomy positive surgical margins occur in the same location as
      extraprostatic extension?
AB  - PURPOSE: Positive surgical margins (PSMs) may reflect incomplete surgical
      resection, while extraprostatic extension (EPE) could suggest that complete tumor
      resection is more difficult. This study evaluated cases with both EPE and PSMs in
      robotic-assisted radical prostatectomy (RARP) specimens to determine the
      respective locations of each. METHODS: A single institutional retrospective
      review of RARP performed between 2007 and 2009 was conducted to identify cases
      with both EPE and PSM. Prostates were entirely submitted and processed in whole
      mount format. All locations of EPE and PSM were recorded as was the size of the
      largest focus of EPE and PSM. RESULTS: About 8.5 % (112/1,315) of RARP had both
      EPE and PSM. Analysis of cases with concurrent EPE and PSM revealed that EPE
      occurred most commonly in the mid-gland, particularly in the posterolateral mid
      prostate. In contrast, PSM was most frequent at the base (bladder neck),
      specifically the anterior base. 51.8 % of the cases had EPE and PSM in discordant
      locations, 19.6 % had EPE and PSM in the same location, and 28.6 % had areas of
      EPE and PSM both in the same location as well as in different locations. Cases
      with both concordant and discordant locations of EPE and PSM had significantly
      more high-risk features including higher tumor volume, more frequent positive
      nodes, and more frequent Gleason score >= 8 compared to concordant or discordant
      subgroups. CONCLUSION: PSMs frequently did not occur in the same location as EPE.
      A better understanding of where EPE and PSMs occur may help guide surgical
      technique to decrease residual tumor.

PMID- 24096433
TI  - Chest X-ray in the follow-up of renal cell carcinoma.
AB  - PURPOSE: To evaluate the value of chest X-ray in the follow-up of surgically
      treated T1-3N0M0 renal cell carcinoma. METHODS: We performed retrospective
      analysis of patients that underwent surgical treatment of a localized renal cell
      carcinoma (T1-3N0M0) between January 1993 and July 2010. Data on frequency and
      results of performed chest X-rays were collected from patients' records. RESULTS:
      In 17.5 years, 249 patients with a T1-3N0M0 renal cell carcinoma underwent a
      radical or partial nephrectomy. In 221 patients, 823 chest X-rays were performed
      during a median follow-up of 3.3 years (range 0.5-17 years). In 19 patients, a
      pulmonary recurrence occurred, of which 10 were not detected by the regular
      follow-up. Of the 9 patients that were diagnosed with a pulmonary recurrence with
      a chest X-ray during follow-up, 7 were asymptomatic at the time of diagnosis, and
      the chest X-ray has led to the detection; 0.85 % of the performed chest X-rays
      (7/823) have led to the detection of asymptomatic lung metastases. CONCLUSIONS:
      Due to the low yield of chest X-ray for detection of asymptomatic pulmonary
      recurrences, it has very low clinical value in the follow-up after nephrectomy
      for T1-3N0M0 renal cell carcinoma.

PMID- 24096435
TI  - Length measurement of the eye using a swept-source interferometer.
AB  - In this article, a swept-source setup based on a semiconductor optical amplifier
      at the central wavelength of 1050 nm for measurements of the axial length inside
      the eye is presented. The large coherence length is achieved using a tunable
      optical filter, consisting of a reflective diffraction grating, two Littrow
      prisms, and a scanner. It was possible to achieve a coherence length of 40 mm,
      which allowed interference measurements in this range to be made. Measurements of
      the biomedical data of a human model eye are presented. To realize faster
      measurements, the data acquisition must be increased to more than 2 MS/s. In
      further studies, the usage of a field-programmable gate array, to achieve faster
      measurements, will be considered.

PMID- 24096436
TI  - Peripartum anesthetic management of patients with Factor XI deficiency.
AB  - INTRODUCTION: Factor XI deficiency is predominantly found in the Ashkenazi Jewish
      population with a prevalence of 9%, but also seen in other ethnicities. Little
      information is available on obstetric anesthesia management in women with Factor
      XI deficiency. Therefore, we undertook a study to evaluate obstetric, anesthetic
      and perinatal outcomes in parturients with Factor XI deficiency. METHODS: A
      retrospective study was conducted with chart reviews from 1996 to 2011 resulted
      in 74 women with Factor XI level deficiency. We compared anesthetic and obstetric
      management in parturients with low (<=30%) level of Factor XI to those with
      higher levels. RESULTS: Ninety-one pregnancy outcomes were reviewed in these 74
      women with Factor XI deficiency. Forty-three women had levels <=30% in 46 labors
      while 31 women had levels >30% in 45 labors. Women with low levels of Factor XI
      were significantly more likely to receive FFP and less likely to receive
      neuroaxial anesthesia. There were no anesthetic complications and no difference
      in mode of delivery or neonatal outcomes. DISCUSSION: This study is the first
      step in building a national database for anesthetic cases and outcomes of
      parturients with Factor XI deficiency. Further efforts must be made to provide
      safe analgesia for these women.

PMID- 24096434
TI  - Prohibitin (PHB) inhibits apoptosis in rat granulosa cells (GCs) through the
      extracellular signal-regulated kinase 1/2 (ERK1/2) and the Bcl family of
      proteins.
AB  - Mammalian ovarian follicular development is tightly regulated by crosstalk
      between cell death and survival signals, which include both endocrine and intra
      ovarian regulators. Whether the follicle ultimately ovulates or undergoes atresia
      is dependent on the expression and actions of factors promoting follicular cell
      proliferation, differentiation or apoptosis. Prohibitin (PHB) is a highly
      conserved, ubiquitous protein that is abundantly expressed in granulosa cells
      (GCs) and associated with GC differentiation and apoptosis. The current study was
      designed to characterize the regulation of anti-apoptotic and pro-apoptotic
      factors in undifferentiated rat GCs (gonadotropin independent phase) governed by
      PHB. Microarray technology was initially employed to identify potential apoptosis
      related genes, whose expression levels within GCs were altered by either
      staurosporine (STS) alone or STS in presence of ectopically over-expressed PHB.
      Next, immunoblot studies were performed to examine the expression patterns of
      selective Bcl-2 family members identified by the microarray analysis, which are
      commonly regulated in the intrinsic-apoptotic pathway. These studies were
      designed to measure protein levels of Bcl2 family in relation to expression of
      the acidic isoform (phosphorylated) PHB and the components of MEK-Erk1/2 pathway.
      These studies indicated that over-expression of PHB in undifferentiated GCs
      inhibit apoptosis which concomitantly results in an increased level of the anti
      apoptotic proteins Bcl2 and Bclxl, reduced release of cytochrome c from
      mitochondria and inhibition of caspase-3 activity. In contrast, silencing of PHB
      expression resulted in change of mitochondrial morphology from the regular
      reticular network to a fragmented form, which enhanced sensitization of these GCs
      to the induction of apoptosis. Collectively, these studies have provided new
      insights on the PHB-mediated anti-apoptotic mechanism, which occurs in
      undifferentiated GCs through a PHB -> Mek-Erk1/2 -> Bcl/Bcl-xL pathway and may
      have important clinical implications.

PMID- 24096437
TI  - Practical application of kangaroo mother care in preterm infants: clinical
      characteristics and safety of kangaroo mother care.
AB  - AIM: To determine the clinical characteristics and safety of kangaroo mother care
      (KMC) according to the gestational age (GA) or postmenstrual age (PMA). METHODS:
      We conducted a prospective clinical study in 31 infants between 25 and 32 weeks'
      GA. The subjects were categorized into two groups (25-28 weeks' and 29-32 weeks'
      GA groups) to compare the clinical characteristics associated with KMC. Heart
      rate, respiratory rate, oxygen saturation, blood pressure and body temperature
      (BT) were longitudinally assessed for 60 min with respect to the PMA group (29-32
      weeks' and 33-36 weeks' PMA groups). RESULTS: The authors analyzed 70 sessions
      with 31 infants (25-32 weeks' GA, birth weight 760-1740 g, 29-36 weeks' PMA). All
      infants had statistically significant higher temperatures during KMC than before
      KMC within clinically acceptable limits (P<0.001). We found a significantly lower
      variation of BT in the 25-28 weeks' GA group compared with the 29-32 weeks' GA
      group at 33-36 weeks' PMA, suggesting accelerated skin maturation in more
      premature infants (P<0.001). CONCLUSION: Our intermittent KMC was a safe and
      feasible method for preterm infants. Notably, at the same PMA, preterm infants in
      the lower at-birth GA group showed an advanced maturation of thermoregulation
      compared with those in the higher GA group.

PMID- 24096438
TI  - Labor induction in nulliparous women with an unfavorable cervix: double balloon
      catheter versus dinoprostone.
AB  - OBJECTIVE: We sought to compare the efficacy of the double-balloon catheter and
      dinoprostone for induction of labor among nulliparous women with an unfavorable
      cervix. STUDY DESIGN: Nulliparous women with a Bishop score <6 were randomized to
      receive a 10-mg intra-vaginal dinoprostone insert or a double-balloon catheter.
      Primary outcome was time to delivery. Statistical analyses were performed by
      intention to treat using the chi-square, Fisher's exact, and Student's t-test, as
      appropriate. RESULTS: The mean induction-to-delivery time was shorter in the
      double-balloon group as compared to the dinoprostone group (17.9+/-5.8 vs. 26.3+/
      9.7 h) as was the time from induction to vaginal delivery (19.13+/-5 vs. 24.45+/
      8.7 h, respectively). More women in the catheter group were delivered within 24 h
      compared to the dinoprostone group (87.1% vs. 47.4%). Approximately 50% of women
      in both groups delivered by cesarean section. CONCLUSION: Induction of labor with
      the double-balloon catheter in nulliparous women with an unfavorable cervix is
      associated with a shorter time to delivery compared to dinoprostone.

PMID- 24096439
TI  - School-based intervention to promote healthy nutrition in Sousse, Tunisia.
AB  - INTRODUCTION: Obesity among children is a major risk factor for chronic diseases.
      School interventions programs can represent a mean to implement healthy nutrition
      attitudes at early ages. Our objective was to evaluate the effects of a school
      intervention program to promote healthy nutrition among adolescents, in terms of
      knowledge, behaviors and intention. METHODS: Quasi experimental study among urban
      students in Sousse, Tunisia with 2 groups, intervention and control. The
      intervention group had an interactive program integrated with school courses that
      promoted healthy nutrition habits. Both groups had a pre post evaluation.
      RESULTS: 2200 students aged from 12 to 16 participated to the pre post
      evaluation. In the intervention group, there were significant changes form pre to
      post test in knowledge, intentions, and behaviors. In the control group, almost
      no significant changes were observed. CONCLUSION: School intervention programs
      can represent an interesting approach to promote healthy nutrition habits among
      adolescents.

PMID- 24096440
TI  - Iranian university students' perceived reproductive health needs.
AB  - AIM: One proposed strategy to improve youth health is needs assessment, a process
      for determining and addressing the needs of individual groups. The aim of this
      study was to explore the attitudes and perceptions of Iranian university students
      toward reproductive health needs, in order to promote the provision of
      reproductive health services. METHODS: Using an anonymous self-administered
      questionnaire, a cross-sectional survey was conducted among 548 students who were
      randomly selected from eight universities in Sari City, Iran. Topics covered the
      participants' attitudes towards reproductive health needs as well as their
      opinion about proper sources of information in this area, as measured using a 5
      point Likert scale. RESULTS: The mean age of participants was 21.57 years, and
      57.82% were female. The maximum score of perceived reproductive health needs was
      related to "Be informed about appropriate behavior with my spouse", and the
      majority of students (82.82%) supported family-based reproductive health
      education with emphasis on the mothers' role. Although 65.14% of the participants
      agreed that "When a young has been raped, it's better that she/he counsel with
      her/his family", 11.67% of them stated that she/he must hide the problem.
      Finally, we found that 60.40% of the students preferred someone in a health care
      center as the one to explain how to use any contraception that may be provided
      for them. CONCLUSION: Taken as a whole, these findings support the critical
      importance of programming for university students as part of a comprehensive
      strategy to improve the health and development of young adults.

PMID- 24096442
TI  - A new and effective way for preventing pre-analytical laboratory errors.

PMID- 24096441
TI  - Immunological screening for tumor cells in serous body fluids has added value
      with the CELL-DYN Sapphire.
AB  - BACKGROUND: Conventional cytological examination has limited sensitivity for
      detecting tumor cells in serous body cavity effusions and therefore, adjuvant
      techniques are necessary for a reliable diagnosis. Flow cytometry has proven
      benefit in these circumstances. The aim of our study was to explore the
      feasibility of CELL-DYN Sapphire, an advanced hematology analyzer with flow
      cytometric capabilities, for detecting tumor cells in serous body fluids, using
      CD326 monoclonal antibodies, which are directed against the epithelial marker
      EpCAM. METHODS: One hundred and five serous fluids (39 peritoneal and 66 pleural
      effusions) were analyzed by the CELL-DYN Sapphire using monoclonal antibody
      combinations CD3/CD19 and CD45/CD326. Of all samples a cytospin preparation was
      made and microscopically examined; the pathology findings served as a reference.
      RESULTS: Using a threshold of 1% CD326+ cells, CELL-DYN Sapphire identified nine
      out of 12 cases with tumor cells in the serous effusions (sensitivity 75%),
      whereas routine cytology found eight cases (sensitivity 67%). The combination of
      immunophenotyping and cytology identified all 12 cases with tumor cells in the
      effusion fluid (sensitivity 100%). The specificities were 92% and 100%,
      respectively. CONCLUSIONS: We demonstrated that it is feasible to run an
      immunophenotypic assay on CELL-DYN Sapphire for detecting tumor cells in serous
      body fluids. In addition, this study confirmed that a combination of conventional
      cytology and flow cytometry had a very high diagnostic yield in cases of
      carcinomatous effusions.

PMID- 24096443
TI  - Assessment of femoral physeal activity after transitory hemiepiphysiodesis using
      screws and nonabsorbable filament.
AB  - BACKGROUND: Different techniques for gradual correction of angular deformities of
      lower limbs exist. Long-term behavior of the growth plate after
      hemiepiphysiodesis is not yet well understood. We assessed the restoration of
      normal physeal activity in New Zealand rabbits, after transitory
      hemiepiphysiodesis, using screws and nonabsorbable filament. METHODS: We
      performed a lateral distal femoral epiphysiodesis using nonabsorbable filament
      and screws, in the right knees of 14 New Zealand male rabbits, aged 11 weeks. Two
      groups were created: in group 1, the suture was cut after 1 month, and in group 2
      it was left uncut. Simple plain radiographs were taken at the beginning and at 4,
      8, and 12 weeks of follow-up to evaluate lower limb deformity rate and femoral
      length. The left knee of each rabbit served as controls. Angular deformity and
      femoral length were compared between the groups. RESULTS: Eleven rabbits
      completed the protocol. The control group had no modification in lower limb
      mechanical axis. On the fourth week, all operated limbs had a significant valgus
      tibiofemoral angle variation (mean 24 degrees, P<0.05). When the filament was
      cut, there was complete restoration of the mechanical axis. When the filament was
      kept, tibiofemoral angle increased its valgus deformity until the eighth week
      (mean 32 degrees) without changes thereafter. The final femoral length was
      shorter in group 2 compared with the other 2 groups (P<0.05), whereas group 1 was
      slightly longer than the control group (P>0.05). CONCLUSIONS: Lateral distal
      femoral hemiepiphysiodesis with nonabsorbable filament resulted in a valgus
      deformity on the femur. Once the filament is cut, the femur can restore its
      normal alignment, while maintaining longitudinal growth. Keeping the physeal
      tether increases the valgus achieved during the first 8 weeks, and remained
      stable throughout the study, shortening the bone. CLINICAL RELEVANCE: This is an
      effective alternative for the correction of angular limb deformities that
      maintains physeal function and may be useful for orthopedic surgeons. It could
      also represent an adequate model for the study of rebound effect.

PMID- 24096444
TI  - Cervicothoracic myelopathy in children with Morquio syndrome A: a report of 4
      cases.
AB  - BACKGROUND: Craniovertebral junction anomalies and C1-C2 instability resulting in
      myelopathy have been well described in the literature on mucopolysaccharidosis IV
      (MPS-IV). Spinal involvement in MPS-IV patients, with neurological impairment,
      other than atlanto-axial instability and thoracolumbar kyphosis, has been
      scarcely mentioned in the literature. METHODS: Retrospective clinical and
      radiologic review of the medical records and imaging studies of 4 individuals
      with Morquio A syndrome, who had undergone decompression and fusion of the
      cervicothoracic spine for myelopathy secondary to cervicothoracic stenosis
      between 1990 and 2009. Data regarding the presence of kyphosis at the
      cervicothoracic and upper thoracic spine, and neurological symptoms and signs
      were obtained. RESULTS: There were 3 girls and 1 boy with an average age of 5
      years and 11 months at presentation with neurological symptoms. Half of the
      patients had previously undergone occipitocervical fusion for atlanto-axial
      instability, whereas the other half were noted to have spinal cord compression at
      both the upper cervical and cervicothoracic regions, and underwent decompression
      and fusion at both levels concomitantly. All patients showed postoperative
      neurological improvement. All patients presented with the classical Morquio
      syndrome vertebral morphology. Cervicothoracic kyphosis was found in all of our
      patients in a varying severity (10 to 35 degrees). Levels of stenosis were
      similar in 3 patients, C7-T2; and occurred at a lower spinal level, T1-T4, in the
      remaining patient. Posterior disk bulging and thecal sac indentation were found
      in all 4 patients. CONCLUSIONS: Neurological problems secondary to progressive
      kyphosis and stenosis at the cervicothoracic and upper thoracic spine are seen in
      children with Morquio syndrome. Early detection with a careful neurological
      assessment, whole spine MR imaging, and appropriate surgical treatment can
      prevent permanent neurological sequelae.

PMID- 24096445
TI  - Trends in pediatric sports-related and recreation-related Injuries in the United
      States in the last decade.
AB  - BACKGROUND: There is an apparent increase in pediatric sports and recreation (SR)
      related injuries in the United States in the last decade. The aim of this study
      was to compare injuries in 2000 to injuries sustained in 2005 and 2010 to
      determine the trend in 8 most common pediatric SR-related injuries in the United
      States in the last decade. METHODS: The National Electronic Injury Surveillance
      System was queried for injuries sustained in the 5- to 14-year age group for the
      8 most common SR-related activities for years 2000, 2005, and 2010. RESULTS:
      Compared with 2000, the musculoskeletal injuries decreased by 10.8% in 2005 and
      12.4% in 2010 for the top 8 SR-related activities in children of 5 to 14 years.
      This corresponded with 13.2% (2005) and 1.1% (2010) decreases in all injuries.
      Controlling for total United States population of children of 5 to 14 years, the
      musculoskeletal injury incidence rate for all 8 SR-related activities decreased
      from 16.4/1000 person-year in 2000 to 14.4/1000 person-year in 2010. Sports
      specific injuries decreased in 6 of 8 SR-related activities from 2000 to 2010.
      The maximal decrease was seen in bicycling (38.1%), roller sports (20.8%), and
      trampolines (17.5%). Football and soccer injuries increased by 22.8% and 10.8%,
      respectively. Compared with children aged 5 to 9 years, children aged 10 to 14
      sustained a greater proportion of total injuries. CONCLUSIONS: The perception
      that pediatric SR injuries in the United States have increased in the last decade
      appears to not be true. The apparent misconception of an increased rate of injury
      may in fact be due to increased severity of injuries, overuse injuries, or
      increased diagnosis, but is not due to increase in the total number of acute
      injuries. Understanding the trend of pediatric SR-related injuries can help
      future injury-prevention efforts. LEVEL OF EVIDENCE: Level IV-prognostic study.

PMID- 24096446
TI  - Treatment of posttraumatic cubitus varus with corrective supracondylar humeral
      osteotomies using the methyl methacrylate external fixator.
AB  - BACKGROUND: In upper and lower extremity fractures and osteotomy fixation, the
      use of methyl methacrylate (MM) as an external fixator presents an alternative
      method. The primary aim of this retrospective study was to evaluate the midterm
      outcome of pediatric patients who underwent corrective humeral supracondylar
      lateral closing-wedge osteotomy, with the external fixation system composed of MM
      and multiplane K-wires. METHODS: Fourteen consecutive cases with cubitus varus,
      who underwent corrective osteotomy with a limited lateral approach stabilized
      with MM and the multiplane K-wires external fixator system between January 2006
      and May 2010, were retrospectively evaluated. Time of union, preoperative and
      postoperative elbow range of motion, and humeroulnar angle were measured. Results
      were rated as excellent, good, or poor, according to Bellemore criteria. RESULTS:
      There were a total of 6 female patients and 8 male patients with a mean age of
      5.7 years (range, 3 to 9 y). The mean follow-up period was 28.2 months (range, 24
      to 48 mo). The mean humeroulnar angle was (-) 18.6 degrees preoperatively, and
      (+) 16.3 degrees at the final follow-up. Thirteen patients were evaluated as
      excellent and 1 patient as good, according to Bellemore criteria. Union was seen
      in all patients at mean 7 weeks (range, 6 to 8 wk). Pin tract infection was
      observed in 1 patient and treated with oral antibiotics. Loss of correction was
      not observed in any patient during follow-up. CONCLUSIONS: External fixation of
      corrective supracondylar humeral osteotomy with MM and multiplane K-wires is a
      practical, effective, reliable, and cheap alternative method that can be applied.
      LEVEL OF EVIDENCE: Level IV. Retrospective study.

PMID- 24096447
TI  - A pediatric case of single-level idiopathic cervical intervertebral disk
      calcification with symptom relapse 1 year after initial onset.
AB  - BACKGROUND: To date there has been only 1 reported case of the symptom relapse of
      pediatric idiopathic intervertebral disk calcification (PIIDC), as described by
      Yoon and colleagues in 1987, who reported symptom relapse in a patient with
      multilevel PIIDC. Thus, symptom relapse in patients with single-level PIIDC have
      not been reported. METHODS: We report here a case of single-level PIIDC with
      symptom relapse 1 year after the initial onset. RESULTS: The patient was a 7-year
      old girl who developed cervical pain and fever up to 38 degrees C without an
      obvious cause. Computed tomography (CT) revealed calcification in the C4/5
      intervertebral disk space and in the epidural space at the C3-5 vertebral levels.
      The patient was diagnosed with PIIDC and treatment with oral nonsteroidal anti
      inflammatory drugs was begun. Both cervical pain and fever gradually improved and
      resolved in approximately 1 week. CT obtained 6 months after the initial onset
      showed calcifications localized in the posterior area of the C4/5 intervertebral
      disk space and reduced epidural calcifications, which had nearly resolved. One
      year after the initial onset, the patient developed similar symptoms. CT revealed
      an enlarged calcified lesion in the epidural space. Thus, the patient was
      diagnosed with symptom relapse of PIIDC. Although there was enlargement of
      calcifications in the epidural space, there were no calcifications involving the
      intervertebral disk at the time of relapse. The patient was treated
      conservatively. Follow-up CT revealed that the lesion resolved with time.
      CONCLUSIONS: This report described a patient with single-level PIIDC and symptom
      relapse 1 year after the initial onset. In the case presented herein,
      calcifications of the intervertebral space had extruded into the epidural space,
      thus causing a symptom relapse. The patient was treated conservatively at the
      initial onset and at the time of relapse. The symptoms improved both times.
      Although patients with single-level PIIDC usually have an uneventful clinical
      course, it is necessary to be mindful of potential symptom relapse.

PMID- 24096448
TI  - Three-dimensional magnetic resonance imaging of physeal injury: reliability and
      clinical utility.
AB  - BACKGROUND: Injuries to the physis are common in children with a subset resulting
      in an osseous bar and potential growth disturbance. Magnetic resonance imaging
      allows for detailed assessment of the physis with the ability to generate 3
      dimensional physeal models from volumetric data. The purpose of this study was to
      assess the interrater reliability of physeal bar area measurements generated
      using a validated semiautomated segmentation technique and to highlight the
      clinical utility of quantitative 3-dimensional (3D) physeal mapping in pediatric
      orthopaedic practice. METHODS: The Radiology Information System/Picture Archiving
      Communication System (PACS) at our institution was searched to find consecutive
      patients who were imaged for the purpose of assessing a physeal bar or growth
      disturbance between December 2006 and October 2011. Physeal segmentation was
      retrospectively performed by 2 independent operators using semiautomated software
      to generate physeal maps and bar area measurements from 3-dimensional spoiled
      gradient recalled echo sequences. Inter-reliability was statistically analyzed.
      Subsequent surgical management for each patient was recorded from the patient
      notes and surgical records. RESULTS: We analyzed 24 patients (12M/12F) with a
      mean age of 11.4 years (range, 5-year to 15-year olds) and 25 physeal bars. Of
      the physeal bars: 9 (36%) were located in the distal tibia; 8 (32%) in the
      proximal tibia; 5 (20%) in the distal femur; 1 (4%) in the proximal femur; 1 (4%)
      in the proximal humerus; and 1 (4%) in the distal radius. The independent
      operator measurements of physeal bar area were highly correlated with a Pearson
      correlation coefficient (r) of 0.96 and an intraclass correlation coefficient for
      average measures of 0.99 (95% confidence interval, 0.97-0.99). Four patients
      underwent resection of the identified physeal bars, 9 patients were treated with
      epiphysiodesis, and 1 patient underwent bilateral tibial osteotomies.
      CONCLUSIONS: Semiautomated segmentation of the physis is a reproducible technique
      for generating physeal maps and accurately measuring physeal bars, providing
      quantitative and anatomic information that may inform surgical management and
      prognosis in patients with physeal injury. LEVEL OF EVIDENCE: Level IV.

PMID- 24096449
TI  - Persisting growth after prophylactic single-screw epiphysiodesis in upper femoral
      epiphysis.
AB  - BACKGROUND: Prophylactic fixation of the contralateral hip in cases of slipped
      upper femoral epiphysis is controversial. Therefore, using a single-cannulated
      screw has been widely accepted. However, differing reports exist on the
      occurrence of persisting growth after prophylactic epiphysiodesis. The aim of
      this retrospective study was to evaluate the presence of persisting growth of the
      upper femoral epiphysis after prophylactic fixation. METHODS: From 2006 until
      2009, 11 children underwent prophylactic pinning using a single-cannulated 6.5-mm
      cancellous screw. Time to fusion, persisting growth, and overgrowing of the screw
      were measured on plain radiographs taken postoperatively and at least after the
      growth plate was fused. RESULTS: All patients except 1 (91%) showed a persisting
      growth of the epiphysis, and in 2 cases a hardware replacement was necessary. The
      mean increase of the femoral neck length was 8.2% (SEM 1.46%). Mean follow-up was
      37 months (range, 12 to 49 mo). All patients had a Risser sign grade 0 at the
      time of surgery, and equal or less than grade 3, when the growth plate was fused.
      CONCLUSIONS: Despite previous reports that a prophylactic fixation using a single
      cannulated cancellous screw is unproblematic and safe, we showed that in our
      series growth persistence was the rule and in some cases the physeal overgrowth
      necessitates a hardware replacement. Careful follow-up until fusion of the growth
      plate should be recommended.

PMID- 24096450
TI  - Space mutagenesis of genetically engineered bacteria expressing recombinant human
      interferon alpha1b and screening of higher yielding strains.
AB  - The aim of this study was to investigate the space mutagenesis of genetically
      engineered bacteria expressing recombinant human interferon alpha1b. The
      genetically engineered bacteria expressing the recombinant interferon alpha1b
      were sent into outer space on the Chinese Shenzhou VIII spacecraft. After the 17
      day space flight, mutant strains that highly expressed the target gene were
      identified. After a series of screening of spaceflight-treated bacteria and the
      quantitative comparison of the mutant strains and original strain, we found five
      strains that showed a significantly higher production of target proteins,
      compared with the original strain. Our results support the notion that the outer
      space environment has unique effects on the mutation breeding of microorganisms,
      including genetically engineered strains. Mutant strains that highly express the
      target protein could be obtained through spaceflight-induced mutagenesis.

PMID- 24096451
TI  - Actual and ideal services in acute care and rehabilitation for relatives post
      stroke from three perspectives: Relatives, stroke clients and health
      professionals.
AB  - OBJECTIVE: To document the gap between actual and desired ideal services for
      relatives post-stroke from three perspectives: relatives, stroke clients and
      health professionals. METHODS: A two-phase qualitative design and consisting of
      in-depth interviews (Phase 1) and 3 focus groups (Phase 2). The interview sample
      consisted of 25 relatives (mean age 53.4 (standard deviation 12.7); women =
      21/25) and 16 individuals with a first stroke (mean age = 55.7 (standard
      deviation 11.2); women = 7/16). The focus group sample size varied from 5 to 7
      participants. An interview guide validated by experts was used. Audio content was
      transcribed verbatim and rigorously analyzed by two team members. RESULTS:
      Services received by relatives are diversified, and relatives' perceptions range
      from receiving no services to being satisfied with services received. Even when
      participants were satisfied, ideal services were still desired: they would have
      liked to receive services earlier and without having to seek. Four main factors
      emerged as influencing the amount and quality of services received, including the
      individual's ability to seek. CONCLUSIONS: A gap remains between actual and ideal
      services for relatives post-stroke. It is crucial to legitimized relatives' role
      as clients and to systematically assess the patient's social environment in order
      to provide services in accordance with needs.

PMID- 24096452
TI  - The 2012 Elliott Youth Development Lecture.

PMID- 24096453
TI  - 'PET' vs. 'push-pull' induced ICT: a remarkable coumarinyl-appended pyrimidine
      based naked eye colorimetric and fluorimetric sensor for the detection of Hg2+
      ions in aqueous media with test trips.
AB  - A novel colorimetric and fluorescent chemosensor based on 7-(diethylamino)-3
      (pyrimidin-4-yl)-2H-chromen-2-one (PYC) has been designed and synthesized for the
      detection of Hg(2+) in the presence of other competing metals in mixed aqueous
      media. The PYC exhibits naked eye color change from green to red, and the
      fluorescence color changes from yellowish green to light orange with Hg(2+). It
      also shows a red shift in wavelength of about 80 nm in absorption spectra. Test
      strips based on PYC were fabricated, which could act as convenient and efficient
      Hg(2+) test kits.

PMID- 24096454
TI  - Phenylalanine catabolism in Archaeoglobus fulgidus VC-16.
AB  - Evidence is presented for a pathway of phenylalanine catabolism in the
      hyperthermophilic archaeon Archaeoglobus fulgidus involving the following enzymes
      phenylalanine:2-oxoglutarate aminotransferase, phenyllactate dehydrogenase,
      radical iron-sulphur 3-phenyllactyl-CoA dehydratase, phenylpropionyl-CoA
      dehydrogenase, aryl pyruvate ferredoxin oxidoreductase, ADP-forming acetyl-CoA
      synthetase and family III CoA-transferase. Hitherto amino acid degradation
      pathways involving radical iron-sulphur dehydratases have been characterised only
      in mesophilic clostridia and related bacteria. The difference here is that the
      pathway is not fermentative but coupled to sulphate reduction. Initial
      experiments also show the utilisation of tryptophan as a growth substrate and the
      decarboxylation of caffeate by cell extracts, suggesting the potential to
      catabolise different classes of aromatic compounds. 

PMID- 24096456
TI  - CORR Insights (r): Cerebral desaturation during shoulder arthroscopy: a
      prospective observational study.

PMID- 24096455
TI  - Is intraarticular pathology common in patients with hip dysplasia undergoing
      periacetabular osteotomy?
AB  - BACKGROUND: Periacetabular osteotomy (PAO) enables correction of bony acetabular
      deficiency in the setting of hip dysplasia. Patients with insufficient acetabular
      coverage often have intraarticular pathology, but the degree of this pathology
      has been incompletely characterized. We have used arthroscopy as an adjunct to
      PAO to further delineate intraarticular pathology in patients with hip dysplasia
      with mechanical symptoms. QUESTIONS/PURPOSES: We documented the arthroscopic
      incidence of (1) femoral and acetabular chondral pathology, (2) femoral neck cam
      lesions, and (3) internal snapping or ligamentum teres pathology among patients
      having arthroscopy before PAO. METHODS: We reviewed all 16 patients (17 hips;
      mean age at surgery, 21 years; range, 12-33 years) with hip dysplasia who
      underwent PAOs and concomitant hip arthroscopy at our institutions from October
      2010 to March 2012. During this period, 80 patients underwent PAOs, making the
      arthroscopic cohort 21% of the total cohort. Indications for concomitant hip
      arthroscopy were mechanical symptoms consistent with labral pathology identified
      on MRI. We documented pathology involving the labrum, chondral surface,
      ligamentum teres, cam deformity, and psoas tendon. RESULTS: Arthroscopy revealed
      significant intraarticular pathology in all patients. Fourteen hips had
      anterosuperior labral tears, and three hips had preoperative findings of internal
      snapping hip. Eleven hips had femoral cam-type lesions in addition to dysplasia,
      and 16 hips had articular chondral injury. Two hips had full-thickness ligamentum
      tears, and 13 hips had partial-thickness tears. CONCLUSIONS: Intraarticular
      pathology at the time of PAO is common. Future studies are needed to rigorously
      address the use of arthroscopic intervention during PAO and the impact on
      clinical outcome compared to PAO alone.

PMID- 24096457
TI  - Association of obesity with inflammation and pain after total hip arthroplasty.
AB  - BACKGROUND: The prevalence of obesity is increasing, and obesity often leads to
      degenerative joint disease requiring total hip arthroplasty (THA). Obesity is a
      proinflammatory state associated with an increase in chronic, low-grade
      inflammatory response. As such, it may augment the postoperative inflammatory
      response, which has been associated with postoperative pain and complications.
      QUESTIONS/PURPOSES: We determined whether severity of obesity was associated with
      (1) severity of inflammatory response, as measured by the in vivo circulating
      levels of cytokines and ex vivo functional reactivity of mononuclear blood cells,
      and (2) severity of pain, as measured by verbal pain scores and analgesic
      consumption, in the first 24 hours after THA. METHODS: We studied 60 patients (20
      normal weight, 20 overweight, 20 obese) undergoing elective primary unilateral
      THA in this prospective cross-sectional study. Blood samples were collected for C
      reactive protein and cytokine levels, including IL-1beta, IL-2, IL-6, IL-8, and
      tumor necrosis factor alpha (TNF-alpha), from patients before and 24 hours after
      surgery. Cytokine response of whole blood was evaluated ex vivo with or without
      two standard activators, phorbol-12-myristate-13-acetate and lipopolysaccharide,
      using standardized blood sample from patients at 24 hours. These standard immune
      activators are implicated in the inflammatory response to gram-negative
      infection, translocation of microbial products, pathophysiology of septic shock
      syndrome in human, and tumor promotion. Pain response was gauged using verbal
      pain scores (on a 0- to 10-point scale, where 0 = no pain and 10 = worst pain) at
      rest and with activity at 24 hours after surgery and analgesic consumption of
      volume of epidural analgesic solution for the first 24 hours after surgery.
      RESULTS: No correlation was found between BMI and postoperative spontaneous
      circulating cytokine levels. However, after activation of blood leukocytes with
      lipopolysaccharide, there was a significant positive correlation between the BMI
      and IL-1beta, IL-6, and TNF-alpha levels (r = 0.26-0.32; p = 0.03, p = 0.03, and
      p = 0.01, respectively), suggesting priming of the innate immune system in
      obesity and potential for excessive postoperative inflammatory response. Obesity
      was not associated with increased pain or analgesic consumption in the first 24
      hours after surgery. CONCLUSIONS: Obesity is associated with a proinflammatory
      state after THA as demonstrated by enhanced cytokine reactivity. Larger studies
      exploring the specific impact of obesity and inflammation on surgical outcomes,
      including pain, are warranted. LEVEL OF EVIDENCE: Level II, therapeutic study.
      See the Instructions for Authors for a complete description of levels of
      evidence.

PMID- 24096459
TI  - [The philosophical foundations of evidence-based nursing].
AB  - As a branch of evidence-based practice, evidence-based nursing emphasizes the
      integration of patient needs, the evidence for practical problem solving, and the
      application of nursing expertise. The criteria of evidence and the application of
      evidence in practice are the central theoretical foundations of evidence-based
      practice and evidence-based nursing. Therefore, the main philosophical
      considerations of evidence-based nursing shall focus on the criteria by which
      evidence supports propositions and how evidence should be applied in practice. In
      this paper, we explain the criteria of evidence from an epistemological
      perspective and explain the application of evidence in practice from the
      perspective of rational decision-making. Finally, we use these philosophical
      considerations to propose practical guidelines for evidence-based nursing and
      explain the philosophical significance of nursing practice. 

PMID- 24096458
TI  - Comparison of acetabular anterior coverage after Salter osteotomy and Pemberton
      acetabuloplasty: a long-term followup.
AB  - BACKGROUND: The Salter osteotomy and Pemberton acetabuloplasty are common
      procedures for a deficient acetabulum in patients with developmental dysplasia of
      the hip. However, the degree of increasing retroversion and anterior acetabular
      coverage of these two procedures remains unanswered. QUESTIONS/PURPOSES: The
      purpose of this study is to show the change in anterior coverage and relevant
      parameters in measuring pain and function among patients who have undergone
      either a Salter osteotomy or Pemberton acetabuloplasty. METHODS: Forty-two
      patients who underwent either a Salter or Pemberton procedure at one institution
      between January 1981 and December 2000 and were available for followup at least
      10 years later (mean, 18 years; range, 12-28 years) were evaluated
      retrospectively. This represented 12% of the Salter and Pemberton procedures
      performed in patients between 12 and 36 months old at our institution during the
      study period. We measured vertical-center-anterior margin angle, anterior
      acetabular head index, and weightbearing zone acetabular index, and we made
      comparisons using the radiographic parameter ratio (the division of each
      radiographic measurement of the operative side by that of the nonoperated side).
      All patients completed SF-36 and Harris hip score questionnaires at followup.
      RESULTS: In the Salter group, there were no differences in vertical-center
      anterior margin angle, anterior acetabular head index, or weightbearing zone
      acetabular index. In the Pemberton group, there was no difference in vertical
      center-anterior margin angle or anterior acetabular head index, but the
      weightbearing zone acetabular index decreased, suggesting increased anterior
      acetabular coverage (surgically treated side, 6 [95% CI, 4.84, 7.16]; nonoperated
      side, 12 [95% CI, 10.07, 13.39]; p < 0.001). Compared with that in the Salter
      group, the weightbearing zone acetabular index ratio was smaller in the Pemberton
      group, which means more acquired anterior coverage after a Pemberton
      acetabuloplasty (Salter procedure, 0.94 [95% CI, 0.70, 1.17], Pemberton
      procedure, 0.53 [95% CI, 0.40, 0.65]; p < 0.001). Three patients in the Pemberton
      group had an anterior impingement sign at followup, whereas none in the Salter
      group did. The SF-36 and Harris hip scores were good and showed no differences
      between the two groups. CONCLUSIONS: Our study suggests the weightbearing zone
      acetabular index on false profile radiographs of the hip, a parameter focusing on
      morphologic features of the anterior acetabulum, decreased after Pemberton
      acetabuloplasty compared with the nonoperated side and after the Salter
      acetabuloplasty. This suggests that by modifying the shape of the acetabulum with
      a hinge in the triradiate cartilage, a Pemberton acetabuloplasty may result in
      increasing acetabular anterior coverage and the risk of hip impingement. However,
      the functional results with at least 10 years followup were good and similar for
      both procedures. LEVEL OF EVIDENCE: Level III, therapeutic study. See the
      Instructions for Authors for a complete description of levels of evidence.

PMID- 24096460
TI  - [The new era of evidence-based nursing: comprehensive mobilization and
      development of the nursing sciences].
AB  - Science is subject to inevitable evolutionary change. Philosopher of science
      Thomas Kuhn defined a scientific revolution as a period in time during which a
      particular field of scientific knowledge is set to transition to a new paradigm
      that will propel it toward a new milestone. Because person-centered care embraces
      the universal values of trans-disciplinary healthcare teams, evidence-based
      healthcare represents a paradigm shift toward evidence-based nursing. The rapid
      development of evidence-based practice is an evolutionary process of
      revolutionary importance to science. The resulting era of evidence-based nursing
      will help fully realize the development potential of the nursing sciences. This
      article introduces the process of knowledge construction in evidence-based
      nursing, reviews the literature to identify the general model used to promote
      evidence-based nursing internationally, and proposes practical strategies to
      promote evidence-based nursing in Taiwan. We hope this article will help further
      promote the clinical application of evidence-based nursing and the development of
      nursing science. 

PMID- 24096461
TI  - [Qualitative translational science in clinical practice].
AB  - Qualitative translational research refers to the "bench-to-bedside" enterprise of
      harnessing knowledge from the basic sciences to produce new treatment options or
      nursing interventions for patients. Three evidence-based translational problems
      related to qualitative translational research discussed this year address the
      interfaces among the nursing paradigm, the basic sciences, and clinical nursing
      work. This article illustrates the definition of translational science and
      translational blocks of evidence-based practice; discusses the qualitative
      research perspective in evidence synthesis, evidence translation and evidence
      utilization; and discusses the research questions that must be answered to solve
      the problems of the three translational gaps from the qualitative research
      perspective. Qualitative inquiry has an essential role to play in efforts to
      improve current healthcare-provider nursing interventions, experiences, and
      contexts. Thus, it is vital to introduce qualitative perspectives into evidence
      based practice from the knowledge discovery through to the knowledge
      implementation process. 

PMID- 24096462
TI  - [Strategy for promoting evidence-based nursing practice in hospital].
AB  - Evidence-based practice has been demonstrated to improve quality of care,
      increase patients' satisfaction, and reduce the costs of medical care. Therefore,
      evidence-based practice is now central to the clinical decision-making process
      and to achieving better quality of care. Today, it is one of the important
      indicators of core competences for healthcare providers and accreditation for
      healthcare and educational systems. Further, evidence-based practice encourages
      in-school and continuous education programs to integrate evidence-based elements
      and concepts into curricula. Healthcare facilities and professional organizations
      proactively host campaigns and encourage healthcare providers to participate in
      evidence-based related training courses. However, the clinical evidence-based
      practice progress is slow. The general lack of a model for organizational follow
      up may be a key factor associated with the slow adoption phenomenon. The authors
      provide a brief introduction to the evidence-based practice model, then described
      how it may be successfully translated through a staged process into the evidence
      based practices of organizational cultures. This article may be used as a
      reference by healthcare facilities to promote evidence-based nursing practice. 

PMID- 24096463
TI  - [The relationship between medication adherence and rehospitalization: a
      prospective study of schizophrenia patients discharged from psychiatric acute
      wards].
AB  - BACKGROUND: Antipsychotics have been regarded as the most effective therapy for
      schizophrenia; however, Taiwan's non-adherence rate for prescribed antipsychotics
      of 50-80% is an important issue that relates directly and significantly to
      schizophrenia patient relapse rates. PURPOSE: This study examines the
      correlational and predictive relationships between medication adherence and
      rehospitalization in schizophrenia patients discharged from an acute ward.
      METHODS: This study used a prospective research design. Schizophrenia patients
      discharged from a psychiatric acute ward who stated their plan to live in the
      community were recruited as participants. Participant medication adherence was
      assessed via home visits during the 6-month follow-up period using scales
      including the Medication Adherence Questionnaire (MAQ), drug attitudes, and
      regimen knowledge. Rehospitalization data were retrieved from electronic medical
      records. Relationships between medication adherence and rehospitalization were
      analyzed using t-tests and regression analysis. RESULTS: Seventy-seven patients
      with schizophrenia discharged from the acute ward were recruited in accordance
      with sampling criteria. The majority were male, young, unmarried, had poorer
      global function, had 12 years of education, and were not rehospitalized during
      the past 6-month period. Using binomial regression analysis, we found the
      relative risk for number of rehospitalizations during the 6-month period to be
      significantly less and the average scores for the total scale, attitude subscale,
      and knowledge subscale of medication adherence to have increased (0.194-0.79
      times). CONCLUSIONS/IMPLICATIONS FOR PRACTICE: Our findings support that better
      medication adherence in people with schizophrenia decreases rehospitalization
      risk. We urge clinicians to develop sensitive interventions to promote
      antipsychotics adherence in this population.

PMID- 24096464
TI  - [The health-related quality of life and bio-psycho-social adaptation effects in
      patients with head and neck cancer: a longitudinal study].
AB  - BACKGROUND: Because of the therapies and methods involved in its treatment, head
      and neck cancer patients often face unpredictable changes in both quality of life
      (QoL) and psychological status over the long course of their disease. Most
      studies have used fixed-term measurements that do not consider time variance and
      its effects. To facilitate medical communication and rehabilitation
      interventions, we investigated changes in HNC (head and neck cancer) patients'
      bio-psycho-social status and QoL over time. PURPOSE: This study examines QoL
      growth patterns and the bio-psycho-social adaptation effect in HNC patients as
      well as how various variables affect within-individual and between-individual
      level factors during the 4 stages of HNC. METHODS: A total of 109 HNC patients
      participated in this study. Two hundred and fifty-seven valid questionnaires were
      gathered. Questionnaires were given to each patient at 4 times: initial disease
      diagnosis; during the therapy period; 3 months after therapy; and 6 months after
      therapy. Descriptive statistics and hierarchical linear models were used in data
      analysis. RESULTS: The main results revealed that: (1) degree of mood disturbance
      decreased linearly as illness stage progressed. Age, gender, religion, and job
      impacted patients' initial status, while gender, cancer stage, and education
      degree were significant moderators of the rate at which a participant's
      adaptation effect grew; (2) patient QoL showed no significant difference over
      time. Age and job were significant impact factors affecting patients' initial
      status. Cancer stage, educational degree, and marital status had a significant
      moderating effect on the growth rate of participants' adaptation effect score.
      CONCLUSIONS AND IMPLICATIONS FOR PRACTICE: Our results indicate that participants
      in this study had a higher level of anxiety and depression than the average
      population and that their QoL was negatively influenced by the side effects of
      their therapy. Therefore, study findings recommend that timely psycho-social
      intervention and side-effect education should be reinforced to enhance patients'
      quality of life.

PMID- 24096465
TI  - [Effects of a walking program on fatigue and exercise capacity in post-surgery
      breast cancer women].
AB  - BACKGROUND: The majority of women with breast cancer experience treatment-related
      fatigue. Fatigue makes patients more inclined to terminate their treatment, which
      influences patient prognosis and survivorship. PURPOSE: This study explores the
      effects of a walking program on fatigue and exercise capacity in women who have
      undergone breast cancer surgery. METHODS: This was a randomized control trial
      study with measures taken 3 times over 5 weeks. Sixty-six women with breast
      cancer were recruited from a medical center in central Taiwan. The intervention
      was a moderate-intensity, home-based walking program. The Functional Assessment
      for Chronic Illness Treatment-Fatigue and distance walked in a 6-minute period,
      respectively, were used to score the main outcome measures of fatigue and
      exercise capacity. RESULTS: For those who accepted chemotherapy, fatigue was
      significantly higher during chemotherapy than after surgery. Although
      participants in the walking program achieved gradually reduced fatigue and
      increased exercise capacity, there was no significant difference in fatigue and
      exercise capacity between the exercise and control groups at any of the three
      measured times. CONCLUSIONS/IMPLICATIONS FOR PRACTICE: Nurse collaboration with
      healthcare providers to promote exercise in the breast cancer population may not
      only improve the health of post-surgery breast cancer women but also enhance the
      independent functioning of nurses and advance the nursing profession.

PMID- 24096467
TI  - [A project to improve psychiatric nursing station air quality].
AB  - BACKGROUND: Ambient air at the psychiatric nursing station in our hospital had
      been notably poor for an extensive period of time. CO2 levels at the station
      averaged 1211 ppm during August, 2009 and a specialist team estimated a CO2
      abnormality ratio of 32%. Analysis identified key issues in three problem areas,
      including (1) ENVIRONMENT: air at the station was not refreshed and electronic
      equipment was in constant operation; (2) Staff: the station had a high staff-to
      space ratio and staffs lacked practical knowledge on indoor air quality
      maintenance; and (3) Policy: the hospital had no guidelines addressing indoor air
      quality maintenance. PURPOSE: The purpose of this project was to reduce ambient
      CO2 levels at the hospital's acute psychiatric ward in order to create a high
      quality working environment for all staff. The short-term goal was to reduce the
      CO2 abnormality ratio from 32% to 10%. Long-term goals were to maintain an
      ambient CO2 level in the ward below 1000ppm and further reduce the abnormality
      ratio to 0%. METHODS: To address environment-related issues, we increased the
      number of indoor plants and turned certain computers off at night. To address
      staff-related issues, we rearranged staff activity space and educated staff on
      how to maintain indoor air quality. To address the policy-related issue, we
      drafted proposed hospital guidelines on indoor air quality maintenance. RESULTS:
      Post-intervention measurements made in October, 2011 found significantly improved
      ambient air quality, with CO2 levels at 997ppm and a CO2 abnormality ratio of 0%.
      CONCLUSIONS: Results demonstrate that improvement measures implemented can
      effectively improve the quality of ambient air at psychiatric nursing stations. A
      post-intervention survey further found that staffs were both more satisfied with
      ward air quality and perceived a friendlier ward work environment.

PMID- 24096466
TI  - [Exploring the lived experiences of middle-aged males diagnosed with chronic
      kidney disease].
AB  - BACKGROUND: The majority of studies addressing chronic kidney disease (CKD) have
      been quantitative. The lived experiences of patients with early stage CKD have
      not been explored in the literature. Due to the lack of symptoms during the early
      stages of CKD, the progress of this disease is often ignored. PURPOSE: This study
      explores the lived experiences of middle-aged males diagnosed with CKD. Research
      focuses on the work experiences, interpersonal relationships, and dietary habits
      of this group. METHODS: This qualitative study used a narrative research method
      with purposive sampling. Ten middle-aged male patients were interviewed. We
      employed the 3 strategies of member checks, peer review, and debriefing in order
      to enhance the trustworthiness of the data analysis. RESULTS: Four major themes
      were identified: (1) keeping the same life pace as usual with concerns of
      deterioration; (2) continuing to support their family and play the role of
      father; (3) hoping to participate in family and friend relationships despite the
      illness; and (4) being challenged to maintain a healthy diet.
      CONCLUSIONS/IMPLICATIONS FOR PRACTICE: Although the physical status of
      participants was similar to the general middle-aged adult population,
      participants were concerned regarding disease deterioration. The results of this
      study suggest that health professionals: (1) provide appropriate information
      based on patients' personality, particularly at the first onset or apparent
      deterioration of the disease; (2) offer specialized healthcare information to
      patients relevant to their career choices; and (3) understand CKD-patient
      difficulties in daily life such as eating out habits and challenges faced in
      maintaining a healthy diet. Results may provide important information to
      healthcare providers in education planning and implementation and support
      programs for patients and families.

PMID- 24096468
TI  - [A project to reduce accidental falls among mentally ill residents in a long-term
      care facility].
AB  - BACKGROUND: Individuals with mental illness are highly vulnerable to personal
      health and safety threats. In recent years, the increasing incidence of
      accidental falls among residents of long-term care facilities has been attributed
      to aging, disease symptoms, and sedative drug effects. PURPOSE: This project
      aimed to reduce the fall incidence rate for mentally ill residents in our
      hospital from 0.0015% to 0.0012% in order to reduce patient injuries and avoid
      the long-term health consequences of these injuries. RESOLUTION: This project was
      conducted between January 1st, 2011 and December 31st, 2011. Our approach
      included direct observation, literature review, meeting discussions, and data
      compilation. The intervention composed four facets: (1) Staff: providing
      education and training skills to prevent patient falls; (2) residents: enhancing
      patient motivation to keep physically fit and assess medication side effects; (3)
      environment: increasing living condition safety; (4) policy: replacing defective
      equipment, performing equipment checks on schedule, and managing a fall
      prevention program. RESULTS: The post-intervention fall incidence rate for
      mentally ill residents was 0.0007%, which was significantly better than our
      target. CONCLUSIONS: We reviewed plans and improved the fall-prevention strategy
      for mentally ill residents of long-term care facilities. This project provides a
      reference for care program planners and administrators.

PMID- 24096469
TI  - [Evidence-based clinical decision making: dietary protein intake recommendations
      for hepatic encephalopathy patients].

PMID- 24096470
TI  - [Psychosocial and caring issues with a bipolar disorder senior inpatient during a
      manic episode].
AB  - This case analysis focuses on a male elderly inpatient with bipolar disorder
      during an acute manic episode. During the case's 3-week hospitalization, we used
      a participant observation approach to provide individualized nursing care. Our
      nursing assessment focused on linking this case's manic symptoms and psychosocial
      issues. Based on a content analysis of our nursing process record and the five
      psychosocial issues of elderly bipolar disorder reported by Reiser et al (2008),
      five major themes were presented. These themes included indulging the memory of
      youth-hood (cohort beliefs); presenting his old but still strong physical
      function (physical health); making an attempt to learn and showing the ability
      (socio-cultural context); providing working expert service and ability
      (transition in role investments); and playing a positive role as a warm
      heartedness senior person (intergenerational relationship). This case's manic
      symptoms and psychosocial issues showed that he wished to perform as a young man
      to compensate for his ageing physical state and psychological loss, which
      revealed he want to maintain his social value. In view of the nursing
      intervention for this case during the acute manic state, we needed to pay
      attention to preventing the patient from physical overexertion and falls. We
      further needed to remind him to drink sufficient water, eat food, and take
      adequate rest. When the acute symptoms were in remission, we tried to empathize
      with and understand his psychosocial issues and self-concept and to help him
      integrate his illness and life experience to accomplish the elderly development
      task. 

PMID- 24096471
TI  - [Improving physiological and psychological status in a hemodialysis patient: a
      nursing experience using an exercise training program].
AB  - Exercise training during hemodialysis has been found to improve functional
      capacity, nutritional status, cardiovascular risk factors, depression, and well
      being in hemodialysis patients. This report describes a nursing experience that
      applied exercise training to improve activity intolerance, powerlessness, and
      ineffective health maintenance in a hemodialysis patient. The care period was
      from May 11 to July 27, 2012. The author collected information using observation,
      interview, physical examination, and medical record review and identified patient
      care problems including activity intolerance, powerlessness, and ineffective
      health maintenance. In addition to providing individual nursing interventions,
      the author designed a stationary bicycle installed at the end of the bed. The
      patient was asked use the bicycle to exercise 30 mins per time, three times per
      week for a period of 12 weeks during the patient's hemodialysis period. Before
      and after a 12-week of exercise training, collected the 6-minute walk test
      (6MWT), self-perceived improvement, and self-reported depression scales were
      performed prior to and after completion of the intervention. Hematological
      triglyceride, albumin, and hemoglobin data were collected each week. Heart rate,
      blood pressure, and oxygen saturation were examined prior to and after the
      intervention to ensure patient safety. After the 12-week intervention, the
      average heart rate achieved 40-60% of the maximum heart rate and the heart rate
      peaked between 85 and 121 bpm. Moreover, the 6MWT distance increased from 210 m
      to 255 m, triglyceride decreased from 622 mg/dL to 173 mg/dL, and self-perceived
      fatigue and depression markedly improved. This nursing experience is shared with
      nurses caring for patients with similar conditions. 

PMID- 24096472
TI  - Clinical spectrum in three families with familial hemiplegic migraine type 2
      including a novel mutation in the ATP1A2 gene.
AB  - INTRODUCTION: Familial hemiplegic migraine (FHM) is a rare subtype of migraine
      with transient hemiplegic aura. PATIENTS AND METHODS: We describe three unrelated
      families with familial hemiplegic migraine type II (FHM2). Retrospectively,
      information on 47 family members could be obtained, 15 by personal examination
      and 32 by indirect anamnesis from relatives. Genetic analyses were performed in
      13 patients. RESULTS: One family had a novel missense mutation in the ATP1A2 gene
      (c.659C>T, p.Ser220Leu) that segregated with the phenotype in three generations.
      Two further unrelated families with different ethnic backgrounds (one from
      Germany and one from Russia) had a missense mutation that has not been described
      as yet in FHM, but occurred in only a single patient with sporadic hemiplegic
      migraine (c.2723G>A, p.Arg908Gln). Clinically the patients had severe attacks
      lasting up to several weeks as well as epileptic seizures. Three patients with a
      proven mutation in the ATP1A2 gene clinically presented without hemiparesis.
      Furthermore, there was a possible relation of FHM2 to mental retardation in
      another two patients. CONCLUSION: Clinical symptoms may last for several weeks in
      some patients. Patients with FHM2 may also present without hemiplegia. Therefore,
      the full family history has to be taken into account to establish the diagnosis
      of FHM.

PMID- 24096473
TI  - Prostate cancer survivors as community health educators: implications for
      informed decision making and cancer communication.
AB  - Recent evidence questioning the effectiveness of prostate-specific antigen
      testing leave community-based prostate cancer (CaP) outreach programs with a
      dilemma between promoting screening and highlighting screening risks. CaP
      survivors are uniquely positioned to address this problem by drawing upon real
      life experiences to share nuanced information and perspectives. While CaP
      survivors have historically been incorporated into outreach programs, little is
      known about their impact on psychosocial outcomes and their effectiveness
      compared to professional health educators. This study addressed these gaps
      through a quasi-experimental design where African American men attended a CaP
      screening session conducted by a health educator (HE) or survivor educator (SV).
      The presentation included prostate cancer statistics, CaP information, and
      descriptions of CaP screening tests. SV were encouraged to bolster their
      presentations with personal stories whereas HE maintained fidelity to the
      curriculum content. All participants completed pre- and post-test questionnaires.
      Our sample comprised a total of 63 participants (HE group = 32; SV group = 31)
      with an age range of 40-70 years. Decision self-efficacy increased significantly
      in the SV group (p = 0.01) whereas perceived screening risks reduced
      significantly in the HE group (p < 0.001). No significant changes were found in
      knowledge, subjective norms, outcome expectancies, and screening benefits.
      Survivor educators were found to have significantly greater appeal (p = 0.03),
      identification with audience (p = 0.01), and liking (p = 0.03). Training CaP
      survivors as health educators might be a viable strategy for community-based
      cancer communication efforts confronted by the CaP screening controversy. We
      discuss conceptual and programmatic implications of our findings and present
      directions for future research.

PMID- 24096475
TI  - Photoinduced processes in a dyad made of a linear and an angular perylene
      bisimide.
AB  - A dyad (PI0-PIa) made of a linear (PI0) and an angular (PIa) perylene
      biscarboximide is synthesized and its spectroscopic, electrochemical and
      photophysical properties investigated in solvents of various polarity. PIa is
      characterized by a high intersystem crossing. The spectroscopy and
      electrochemistry data point to a modest electronic coupling. LUMO-LUMO electron
      transfer from the singlet excited state PI0-1PIa is thermodynamically feasible in
      polar solvents but its occurrence is precluded by a very fast energy transfer to
      yield 1PI0-PIa, k(en) >= 10(11) s(-1). A HOMO-HOMO electron transfer in the
      latter state in polar solvents is precluded by the poor driving force, the
      reaction being unable to compete with the radiative deactivation of the excited
      state. The efficient energy transfer process is quantitatively examined in the
      frame of current theories and ascribed to a dipole-dipole (Forster) mechanism.

PMID- 24096474
TI  - Bio-inspired voltage-dependent calcium channel blockers.
AB  - Ca(2+) influx via voltage-dependent CaV1/CaV2 channels couples electrical signals
      to biological responses in excitable cells. CaV1/CaV2 channel blockers have broad
      biotechnological and therapeutic applications. Here we report a general method
      for developing novel genetically encoded calcium channel blockers inspired by
      Rem, a small G-protein that constitutively inhibits CaV1/CaV2 channels. We show
      that diverse cytosolic proteins (CaVbeta, 14-3-3, calmodulin and CaMKII) that
      bind pore-forming alpha1-subunits can be converted into calcium channel blockers
      with tunable selectivity, kinetics and potency, simply by anchoring them to the
      plasma membrane. We term this method 'channel inactivation induced by membrane
      tethering of an associated protein' (ChIMP). ChIMP is potentially extendable to
      small-molecule drug discovery, as engineering FK506-binding protein into
      intracellular sites within CaV1.2-alpha1C permits heterodimerization-initiated
      channel inhibition with rapamycin. The results reveal a universal method for
      developing novel calcium channel blockers that may be extended to develop probes
      for a broad cohort of unrelated ion channels.

PMID- 24096476
TI  - Phosphorylation of paxillin confers cisplatin resistance in non-small cell lung
      cancer via activating ERK-mediated Bcl-2 expression.
AB  - Paxillin (PXN) is required for receptor tyrosine kinase-mediated ERK activation,
      and the activation of the Raf/MEK/ERK cascade has been linked with Bcl-2
      expression. We hypothesized that phosphorylation of PXN by the EGFR/Src pathway
      might contribute to cisplatin resistance via increased Bcl-2 expression. We show
      that cisplatin resistance was dependent on PXN expression, as evidenced by PXN
      overexpression in TL-13 and TL-10 cells and PXN knockdown in H23 and CL1-5 cells.
      Specific inhibitors of signaling pathways indicated that the phosphorylation of
      PXN at Y118 and Y31 via the Src pathway was responsible for cisplatin resistance.
      We further demonstrated that ERK activation was also dependent on this PXN
      phosphorylation. Bcl-2 transcription was upregulated by phosphorylated PXN
      mediated ERK activation via increased binding of phosphorylated CREB to the Bcl-2
      promoter. A subsequent increase in Bcl-2 levels by a PXN/ERK axis was responsible
      for the resistance to cisplatin. Animal models further confirmed the findings of
      in vitro cells indicating that xenograft tumors induced by TL-13-overexpressing
      cells were successfully suppressed by cisplatin combined with Src or ERK
      inhibitor compared with treatment of cisplatin, Src inhibitor or ERK inhibitor
      alone. A positive correlation of phosphorylated PXN with phosphorylated ERK and
      Bcl-2 was observed in lung tumors from NSCLC patients. Patients with tumors
      positive for PXN, phosphorylated PXN, phosphorylated ERK and Bcl-2 more commonly
      showed a poorer response to cisplatin-based chemotherapy than did patients with
      negative tumors. Collectively, PXN phosphorylation might contribute to cisplatin
      resistance via activating ERK-mediated Bcl-2 transcription. Therefore, we suggest
      that Src or ERK inhibitor might be helpful to improve the sensitivity for
      cisplatin-based chemotherapy in NSCLC patients with PXN-positive tumors. 

PMID- 24096477
TI  - MDM2's social network.
AB  - MDM2 is considered a hub protein due to its capacity to interact with a large
      number of different partners of which p53 is most well described. MDM2 is an E3
      ubiquitin ligase, and many, but not all, of its interactions relate directly to
      this activity, such as substrates, adaptors or bridges, promoters, inhibitors or
      complementary factors. Some interactions serve regulatory functions that in
      response to cellular stresses control the localisation and functions of MDM2
      including protein kinases, ribosomal proteins and proteases. Moreover,
      interactions with nucleotides serve other functions such as mRNA to regulate
      protein synthesis and DNA to control transcription. To perform such a pleiotropic
      panorama of different functions, MDM2 is subjected to a multitude of post
      translational modifications and is expressed in different isoforms. The large and
      diverse interactome is made possible due to the plasticity of MDM2 and in this
      review we have listed the MDM2 interactions until now and we will discuss how
      this multifaceted protein can interact with such a variety of substrates to
      provide a key intermediary role in different signalling pathways. 

PMID- 24096478
TI  - HOXB13 downregulates intracellular zinc and increases NF-kappaB signaling to
      promote prostate cancer metastasis.
AB  - Characteristically, prostate cancer (PCa) cells exhibit marked decrease in
      intracellular zinc; however, the mechanism responsible is not clearly understood.
      HOXB13 is involved in PCa progression and is overexpressed in castration
      resistant PCa. DNA microarray analysis of LNCaP Pca cells showed that ZnT zinc
      output transporters were strikingly upregulated among androgen-independent HOXB13
      target genes. Furthermore, exogenous HOXB13 caused intracellular zinc
      concentrations to fall in PCa cells, stimulated NF-kappaB-mediated signaling by
      reducing inhibitor of NF-kappaB alpha (IkappaBalpha) and enhanced the nuclear
      translocation of RelA/p65. Human prostate tumors also exhibited strong inverse
      correlation between the protein expressions of HOXB13 and IkappaBalpha.
      Consequently, HOXB13 stimulated PCa cell invasion, and this was inhibited by the
      suppression of ZnT4. In addition, studies in a PC3 orthotopic mouse model of PCa
      metastasis showed that HOXB13 is a strong metastatic stimulator. Taken together,
      these results show that HOXB13 promotes PCa invasion and metastasis by decreasing
      intracellular zinc levels, thus stimulating NF-kappaB signals, and suggest that
      HOXB13 acts as a modulator of intracellular zinc levels that promotes the
      malignant characteristics of PCa. 

PMID- 24096479
TI  - Helicobacter pylori generates cells with cancer stem cell properties via
      epithelial-mesenchymal transition-like changes.
AB  - Helicobacter pylori infection is the major risk factor for gastric
      adenocarcinoma. The link with gastric adenocarcinoma is partly due to the H.
      pylori CagA oncoprotein. CagA is responsible for a particular cell phenotype in
      vitro, the 'hummingbird' phenotype, that corresponds to an elongation of the
      cells, mimicking an epithelial-mesenchymal transition (EMT). EMT participates in
      the carcinogenesis process, and is involved in the generation of cancer stem
      cells (CSCs). However, its involvement in gastric carcinogenesis has yet not been
      studied. Therefore, the aim of this study was to determine the role of H. pylori
      in EMT and in the emergence of gastric CSCs. For this purpose, gastric epithelial
      cells were cocultured with a cagA-positive H. pylori strain or its isogenic
      deleted mutants or were transfected with CagA expression vectors. Study of the
      expression of epithelial and mesenchymal markers showed that H. pylori, via CagA,
      is responsible for an EMT phenotype associated with an increase in mesenchymal
      markers as well as CD44 expression, a known gastric CSC marker. Moreover,
      infection led to an increased ability to migrate, to invade and to form
      tumorspheres. Cell sorting experiments showed that only the CD44(high) cells
      induced by H. pylori infection displayed the mesenchymal phenotype and CSC
      properties in vitro, and had higher tumorigenic properties than CD44(low) cells
      in xenografted mice. Immunohistochemistry analyses on human and mouse gastric
      mucosa tissue samples confirmed a high expression of CD44 and mesenchymal markers
      in H. pylori-infected cases, and in gastric dysplasia and carcinoma. All of these
      data suggest that H. pylori, via CagA, unveils CSC-like properties by induction
      of EMT-like changes in gastric epithelial cells. 

PMID- 24096480
TI  - Identification of epithelial stromal interaction 1 as a novel effector downstream
      of Kruppel-like factor 8 in breast cancer invasion and metastasis.
AB  - Kruppel-like factor 8 (KLF8) is a transcriptional factor critical for metastatic
      progression of breast cancer. Epithelial stromal interaction 1 (EPSTI1), a
      recently identified stromal fibroblast-induced gene in non-invasive breast cancer
      cells is highly overexpressed in invasive breast carcinomas. The function and
      regulation of EPSTI1, however, remain largely unknown. In this paper, we report a
      novel KLF8 to EPSTI1 signaling pathway in breast cancer. Using various expression
      analyses, we revealed a high co-overexpression of KLF8 and EPSTI1 in invasive
      human breast cancer cells and patient tumors. Ectopic overexpression of KLF8 in
      the non-invasive MCF-10A cells induced the EPSTI1 expression, whereas KLF8
      knockdown from the invasive, MDA-MB-231 cells decreased the EPSTI1 expression.
      Promoter activation and binding analyses indicated that KLF8 promoted the EPSTI1
      expression by directly acting on the EPSTI1 gene promoter. EPSTI1 knockdown
      dramatically reduced the KLF8-promoted MCF-10A cell invasion, and ectopic
      expression of EPSTI1 in the non-invasive MCF-7 cells is sufficient to induce the
      cell invasion. Experiments using nude mice demonstrated that the ectopic EPSTI1
      granted the MCF-7 cells capability of both invasive growth in the breasts and
      metastasis to the lungs. Using co-immunoprecipitation coupled with mass
      spectrometry, we discovered that EPSTI1 interacts with the valosin-containing
      protein (VCP), resulting in the degradation of IkappaBalpha and subsequent
      activation of NF-kappaB in the nucleus. These findings suggest a novel KLF8 to
      EPSTI1 to VCP to NF-kappaB signaling mechanism potentially critical for breast
      cancer invasion and metastasis.

PMID- 24096482
TI  - mTORC1/2 targeted by n-3 polyunsaturated fatty acids in the prevention of mammary
      tumorigenesis and tumor progression.
AB  - Although epidemiological and preclinical studies have shown the preventative
      effects of n-3 polyunsaturated fatty acids (PUFAs) on breast cancer,
      inconsistencies still remain in the data and the underlying mechanisms remain
      unclear. In this study, we identified mammalian target of rapamycin (mTOR)
      signaling, which plays an essential role in cell proliferation and breast
      tumorigenesis, as a target of n-3 PUFAs. In breast cancer cell lines, n-3 PUFAs
      rapidly and efficiently suppress both mTOR complex 1 (mTORC1) and mTORC2 and
      their downstream signaling, and subsequently inhibit cell proliferation and
      angiogenesis while promoting apoptosis. Further study indicates that
      stabilization of the mTOR-raptor complex by n-3 PUFAs may contribute to their
      inhibitory effect on mTORC1. Importantly, four complementary and well-controlled
      animal models were utilized to identify the role and molecular target of n-3
      PUFAs in the prevention of breast carcinogenesis and progression, namely: (1)
      chemically induced mammary tumor rats with a high dietary intake of n-3 PUFAs;
      (2) nude mice implanted with mammary tumor cell lines stably expressing fat-1, a
      desaturase that catalyzes the conversion of n-6 to n-3 PUFAs and produces n-3
      PUFAs endogenously; (3) fat-1 transgenic severe combined immune deficiency mice
      implanted with breast tumor cells; and (4) the fat-1 transgenic mouse mammary
      tumor virus-polyoma virus middle T oncogene double-hybrid mice, a model of
      aggressive breast cancer. In summary, dietary and endogenous n-3 PUFAs abrogate
      the activity of mTORC1/2 pathways in vitro and in vivo and prevent breast
      carcinogenesis, tumor growth and metastasis. Taken together, our findings
      convincingly clarify the causal relationship between n-3 PUFAs and breast cancer
      prevention and establish mTORC1/2 as a target of n-3 PUFAs. 

PMID- 24096481
TI  - p53-dependent gene repression through p21 is mediated by recruitment of E2F4
      repression complexes.
AB  - The p53 tumor suppressor protein is a major sensor of cellular stresses, and upon
      stabilization, activates or represses many genes that control cell fate
      decisions. While the mechanism of p53-mediated transactivation is well
      established, several mechanisms have been proposed for p53-mediated repression.
      Here, we demonstrate that the cyclin-dependent kinase inhibitor p21 is both
      necessary and sufficient for the downregulation of known p53-repression targets,
      including survivin, CDC25C, and CDC25B in response to p53 induction. These same
      targets are similarly repressed in response to p16 overexpression, implicating
      the involvement of the shared downstream retinoblastoma (RB)-E2F pathway. We
      further show that in response to either p53 or p21 induction, E2F4 complexes are
      specifically recruited onto the promoters of these p53-repression targets.
      Moreover, abrogation of E2F4 recruitment via the inactivation of RB pocket
      proteins, but not by RB loss of function alone, prevents the repression of these
      genes. Finally, our results indicate that E2F4 promoter occupancy is globally
      associated with p53-repression targets, but not with p53 activation targets,
      implicating E2F4 complexes as effectors of p21-dependent p53-mediated repression.

PMID- 24096483
TI  - Post-translational modifications and the Warburg effect.
AB  - Post-translational modification (PTM) is an important step of signal transduction
      that transfers chemical groups such as phosphate, acetyl and glycosyl groups from
      one protein to another protein. As most of the PTMs are reversible, normal cells
      use PTMs as a 'switch' to determine the resting and proliferating state of cells
      that enables rapid and tight regulation of cell proliferation. In cancer cells,
      activation of oncogenes and/or inactivation of tumor suppressor genes provide
      continuous proliferative signals in part by adjusting the state of diverse PTMs
      of effector proteins that are involved in regulation of cell survival, cell cycle
      and proliferation, leading to abnormally fast proliferation of cancer cells. In
      addition to dysregulated proliferation, 'altered tumor metabolism' has recently
      been recognized as an emerging cancer hallmark. The most common metabolic
      phenotype of cancer is known as the Warburg effect or aerobic glycolysis that
      consists of increased glycolysis and enhanced lactate production even in the
      presence of oxygen. Although Otto Warburg observed aerobic glycolysis nearly 90
      years ago, the detailed molecular mechanisms how increased glycolysis is
      regulated by oncogenic and/or tumor suppressive signaling pathways remain
      unclear. In this review, we summarize recent advances revealing how these
      signaling pathways reprogram metabolism through diverse PTMs to provide a
      metabolic advantage to cancer cells, thereby promoting tumor cell proliferation,
      tumorigenesis and tumor growth. 

PMID- 24096484
TI  - c-Abl and Arg induce cathepsin-mediated lysosomal degradation of the NM23-H1
      metastasis suppressor in invasive cancer.
AB  - Metastasis suppressors comprise a growing class of genes whose downregulation
      triggers metastatic progression. In contrast to tumor suppressors, metastasis
      suppressors are rarely mutated or deleted, and little is known regarding the
      mechanisms by which their expression is downregulated. Here, we demonstrate that
      the metastasis suppressor, NM23-H1, is degraded by lysosomal cysteine cathepsins
      (L,B), which directly cleave NM23-H1. In addition, activation of c-Abl and Arg
      oncoproteins induces NM23-H1 degradation in invasive cancer cells by increasing
      cysteine cathepsin transcription and activation. Moreover, c-Abl activates
      cathepsins by promoting endosome maturation, which facilitates trafficking of
      NM23-H1 to the lysosome where it is degraded. Importantly, the invasion- and
      metastasis-promoting activity of c-Abl/Arg is dependent on their ability to
      induce NM23-H1 degradation, and the pathway is clinically relevant as c-Abl/Arg
      activity and NM23-H1 expression are inversely correlated in primary breast
      cancers and melanomas. Thus, we demonstrate a novel mechanism by which cathepsin
      expression is upregulated in cancer cells (via Abl kinases). We also identify a
      novel role for intracellular cathepsins in invasion and metastasis (degradation
      of a metastasis suppressor). Finally, we identify novel crosstalk between
      oncogenic and metastasis suppressor pathways, thereby providing mechanistic
      insight into the process of NM23-H1 loss, which may pave the way for new
      strategies to restore NM23-H1 expression and block metastatic progression. 

PMID- 24096485
TI  - Targeting cancer stem cells to suppress acquired chemotherapy resistance.
AB  - Acquired resistance has curtailed cancer survival since the dawn of the
      chemotherapy age more than half a century ago. Although the application of stem
      cell (SC) concepts to cancer captured the imagination of scientists for many
      years, only the last decade has yielded substantial evidence that cancer SCs
      (CSCs) contribute to chemotherapy resistance. Recent studies suggest that the
      functional and molecular properties of CSCs constitute therapeutic opportunities
      to improve the efficacy of chemotherapy. Here we review how these properties have
      stimulated combination strategies that suppress acquired resistance across a
      spectrum of malignancies. The clinical implementation of these strategies
      promises to rejuvenate the effort against an enduring challenge. 

PMID- 24096487
TI  - Cell competition may function either as tumour-suppressing or as tumour
      stimulating factor in Drosophila.
AB  - Drosophila endocytosis-defective cells develop tumour overgrowths in the imaginal
      discs. We have analysed the tumorigenic potential of cells mutant for Rab5, a
      gene involved in endocytosis. We found that while a compartment entirely made by
      Rab5 mutant cells can grow indefinitely, clones of Rab5 cells surrounded by
      normal cells are eliminated by cell competition. However, when a group of about
      400 cells are simultaneously made mutant for Rab5, they form an overgrowing
      tumour: mutant cells in the periphery are eliminated, but those inside survive
      and continue proliferating because they are beyond the range of cell competition.
      These results identify group protection as a mechanism to evade the tumour
      suppressing function of cell competition in Drosophila. Furthermore, we find that
      the growth of the tumour depends to a large extent on the presence of apoptosis
      inside the tumour: cells doubly mutant for Rab5 and the proapoptotic gene dronc
      do not form overgrowing tumours. These results suggest that the apoptosis caused
      by cell competition acts as a tumour-stimulating factor, bringing about high
      levels of Jun N-terminal kinase and subsequently Wg/Dpp signalling and high
      proliferation levels in the growing tumour. We conclude that under these
      circumstances cell competition facilitates the progression of the tumour, thus
      reversing its normal antitumour role. 

PMID- 24096486
TI  - microRNA-10b enhances pancreatic cancer cell invasion by suppressing TIP30
      expression and promoting EGF and TGF-beta actions.
AB  - Increased microRNA-10b (miR-10b) expression in the cancer cells in pancreatic
      ductal adenocarcinoma (PDAC) is a marker of disease aggressiveness. In the
      present study, we determined that plasma miR-10b levels are significantly
      increased in PDAC patients by comparison with normal controls. By gene profiling,
      we identified potential targets downregulated by miR-10b, including Tat
      interacting protein 30 (TIP30). Immunoblotting and luciferase reporter assays
      confirmed that TIP30 was a direct miR-10b target. Downregulation of TIP30 by miR
      10b or siRNA-mediated silencing of TIP30 enhanced epidermal growth factor (EGF)
      dependent invasion. The actions of miR-10b were abrogated by expressing a
      modified TIP30 cDNA resistant to miR-10b. EGF-induced EGF receptor (EGFR)
      tyrosine phosphorylation and extracellular signal-regulated kinase
      phosphorylation were enhanced by miR-10b, and these effects were mimicked by
      TIP30 silencing. The actions of EGF in the presence of miR-10b were blocked by
      EGFR kinase inhibition with erlotinib and by dual inhibition of PI3K
      (phosphatidylinositol 3'-kinase) and MEK. Moreover, miR-10b, EGF and transforming
      growth factor-beta (TGF-beta) combined to markedly increase cell invasion, and
      this effect was blocked by the combination of erlotinib and SB505124, a type I
      TGF-beta receptor inhibitor. miR-10b also enhanced the stimulatory effects of EGF
      and TGF-beta on cell migration and epithelial-mesenchymal transition (EMT) and
      decreased the expression of RAP2A, EPHB2, KLF4 and NF1. Moreover, miR-10b
      overexpression accelerated pancreatic cancer cell (PCC) proliferation and tumor
      growth in an orthotopic model. Thus, plasma miR-10b levels may serve as a
      diagnostic marker in PDAC, whereas intra-tumoral miR-10b promotes PCC
      proliferation and invasion by suppressing TIP30, which enhances EGFR signaling,
      facilitates EGF-TGF-beta cross-talk and enhances the expression of EMT-promoting
      genes, whereas decreasing the expression of several metastasis-suppressing genes.
      Therefore, therapeutic targeting of miR-10b in PDAC may interrupt growth
      promoting deleterious EGF-TGF-beta interactions and antagonize the metastatic
      process at various levels. 

PMID- 24096490
TI  - Cs2.91Na1.34Fe(3+)0.25[Fe3O(SO4)6(H2O)3].5H2O, a member of the Maus's salt
      family.
AB  - The title compound, tricaesium sodium iron(III) MU3-oxido-hexa-MU2-sulfato
      tris[aquairon(III)] pentahydrate, Cs2.91Na1.34Fe(3+)0.25[Fe3O(SO4)6(H2O)3].5H2O,
      belongs to the family of Maus's salts, K5[Fe3O(SO4)6(H2O)3].6H2O, which is based
      on the triaqua-MU3-oxido-hexa-MU-sulfato-triferrate(III) anion,
      [Fe3O(SO4)6(H2O)3](5-), with Fe in a characteristically distorted octahedral
      coordination environment, sharing a common corner via an oxide O atom. Cs in four
      different cation sites, Na in three different cation sites and five water
      molecules link the anions in three dimensions and set up a crystal structure in
      which those parts parallel to (001) and within 0.05 < z < 0.95 have a distinct
      trigonal pseudosymmetry, whereas the cation arrangement and bonding near z ~ 0
      generate a clear-cut noncentrosymmetric polar edifice with the monoclinic space
      group C2. The structure shows some cation disorder in the region near z ~ 1/2
      where one Na atom in octahedral coordination is partly substituted by Fe(3+), and
      a Cs atom is substituted by small amounts of Na on a separate nearby site. One Na
      atom, located on a twofold axis at z = 0 and tetrahedrally coordinated by four
      sulfate O atoms of two [Fe3O(SO4)6(H2O)3](5-) units, plays a key role in
      generating the noncentrosymmetric structure. Three of the seven different cation
      sites are on twofold axes (one Na(+) site and two Cs(+) sites), and all other
      atoms of the structure are in general positions.

PMID- 24096491
TI  - The polar phase of Li2Ge4O9 at 298, 150 and 90 K.
AB  - Dilithium tetragermanate is orthorhombic, space group P2(1)ca, at 298 K, and is
      thus in a polar and probably a ferroelectric state. The structure contains two
      independent Li, four Ge and nine O atoms, all on general positions with site
      symmetry 1. Three tetrahedrally coordinated Ge positions form crumpled crankshaft
      like chains, forming sheets within the ac plane, and these are interconnected by
      the fourth, octahedrally coordinated, Ge sites along the b direction. The GeO4
      tetrahedra and GeO6 octahedra form a three-dimensional framework containing two
      different cavities, hosting the two 4+1-coordinated Li sites. Cooling to 90 K
      does not alter the space-group symmetry; the tetrahedral chains behave as a rigid
      unit and changes occur mainly within the Li coordination spheres.

PMID- 24096492
TI  - Electrochemical properties of a cobalt(II) complex with sulfadiazine and 1,3
      bis(pyridin-4-yl)propane.
AB  - catena-Poly[[bis{4-[(pyrimidin-2-ylazanidyl)sulfonyl]aniline}cobalt(II)]-bis[MU
      1,3-bis(pyridin-4-yl)propane]], [Co(C10H8N4O4S2)2(C13H14N2)]n or [Co(L)2(bpp)]n,
      crystallizes as a one-dimensional polymeric structure which is further stabilized
      by intermolecular hydrogen bonding. The refined Flack parameter, -0.001 (10),
      indicates that the model represents the correct absolute structure. Investigation
      of the thermal stability shows that the complex is stable up to 543 K. The
      structure is of interest with respect to its electrochemical properties in the
      reduction reaction of H2O2 to H2O. 

PMID- 24096489
TI  - EYA4 is inactivated biallelically at a high frequency in sporadic lung cancer and
      is associated with familial lung cancer risk.
AB  - In an effort to identify novel biallelically inactivated tumor suppressor genes
      (TSGs) in sporadic invasive and preinvasive non-small-cell lung cancer (NSCLC)
      genomes, we applied a comprehensive integrated multiple 'omics' approach to
      investigate patient-matched, paired NSCLC tumor and non-malignant parenchymal
      tissues. By surveying lung tumor genomes for genes concomitantly inactivated
      within individual tumors by multiple mechanisms, and by the frequency of
      disruption in tumors across multiple cohorts, we have identified a putative lung
      cancer TSG, Eyes Absent 4 (EYA4). EYA4 is frequently and concomitantly deleted,
      hypermethylated and underexpressed in multiple independent lung tumor data sets,
      in both major NSCLC subtypes and in the earliest stages of lung cancer. We found
      that decreased EYA4 expression is not only associated with poor survival in
      sporadic lung cancers but also that EYA4 single-nucleotide polymorphisms are
      associated with increased familial cancer risk, consistent with EYA4s proximity
      to the previously reported lung cancer susceptibility locus on 6q. Functionally,
      we found that EYA4 displays TSG-like properties with a role in modulating
      apoptosis and DNA repair. Cross-examination of EYA4 expression across multiple
      tumor types suggests a cell-type-specific tumorigenic role for EYA4, consistent
      with a tumor suppressor function in cancers of epithelial origin. This work shows
      a clear role for EYA4 as a putative TSG in NSCLC. 

PMID- 24096488
TI  - Impaired DICER1 function promotes stemness and metastasis in colon cancer.
AB  - Disruption of microRNA (miRNA) expression patterns is now being recognized as a
      hallmark of human cancer. The causes of these altered profiles are diverse, and,
      among them, we found the existence of defects in the miRNA processing machinery.
      However, little is known about how these alterations affect the biology of the
      underlying tumors. Herein, we show that colorectal cancer cells with an
      impairment in DICER1, a major miRNA biogenesis gene, undergo enrichment of tumor
      stemness features and an epithelial-to-mesenchymal transition. These phenotypes
      are associated with the downregulation of miRNAs, such as miR-34a, miR-126 and
      those of the miR-200 family, that target critical coding genes in these pathways.
      Most importantly, DICER1 impairment also induces the acquisition of a greater
      capacity for tumor initiation and metastasis, two properties associated with
      cancer stem cells.

PMID- 24096493
TI  - The double-stranded ladder-like structure of poly[[bis(MU2-acetato
      kappa(2)O:O')bis(acetato-kappaO)bis(MU-4,4'-bipyridine-kappa(2)N:N')dicopper(II)]
      4-nitrophenol disolvate tetrahydrate].
AB  - The reaction of 4,4'-bipyridine with copper acetate in the presence of 4
      nitrophenol led to the formation of the title compound,
      {[Cu(CH3COO)2(C10H8N2)].C6H5NO3.2H2O}n. The complex forms a double-stranded
      ladder-like coordination polymer extending along the b axis. The double-stranded
      polymers are separated by 4-nitrophenol and water solvent molecules. The two
      Cu(II) centres of the centrosymmetric Cu2O2 ladder rungs have square-pyramidal
      coordination environments, which are formed by two acetate O atoms and two 4,4'
      bipyridine N atoms in the basal plane and another acetate O atom at the apex. The
      ladder-like double strands are separated from each other by one unit-cell length
      along the c axis, and are connected by the water and 4-nitrophenol molecules
      through a series of O-H...O and C-H...O hydrogen-bonding interactions and two
      unique intermolecular pi-pi interactions.

PMID- 24096494
TI  - Chloridobis[2-(diphenylphosphanyl)ethanamine-kappa(2)P,N](triphenylphosphane
      kappaP)ruthenium(II) chloride toluene monosolvate.
AB  - The aminophosphane ligand 1-amino-2-(diphenylphosphanyl)ethane [Ph2P(CH2)2NH2]
      reacts with dichloridotris(triphenylphosphane)ruthenium(II), [RuCl2(PPh3)3], to
      form chloridobis[2-(diphenylphosphanyl)ethanamine-kappa(2)P,N](triphenylphosphane
      kappaP)ruthenium(II) chloride toluene monosolvate,
      [RuCl(C18H15P)(C14H16NP)2]Cl.C7H8 or [RuCl(PPh3){Ph2P(CH2)2NH2}2]Cl.C7H8. The
      asymmetric unit of the monoclinic unit cell contains two molecules of the Ru(II)
      cation, two chloride anions and two toluene molecules. The Ru(II) cation is
      octahedrally coordinated by two chelating Ph2P(CH2)2NH2 ligands, a
      triphenylphosphane (PPh3) ligand and a chloride ligand. The three P atoms are
      meridionally coordinated, with the Ph2P- groups from the ligands being trans. The
      two -NH2 groups are cis, as are the chloride and PPh3 ligands. This chiral
      stereochemistry of the [RuCl(PPh3){Ph2P(CH2)2NH2}2](+) cation is unique in
      ruthenium-aminophosphane chemistry. 

PMID- 24096495
TI  - 2,5-Bis[4-methyl-3-(pyridin-3-yl)phenyl]-1,3,4-oxadiazole and its one-dimensional
      polymeric complex with ZnCl2.
AB  - 2,5-Bis[4-methyl-3-(pyridin-3-yl)phenyl]-1,3,4-oxadiazole (L), C26H20N4O, forms
      one-dimensional chains via two types of intermolecular pi-pi interactions. In
      catena-poly[[dichloridozinc(II)]-MU-2,5-bis[4-methyl-3-(pyridin-3-yl)phenyl]
      1,3,4-oxadiazole], [ZnCl2(C26H20N4O)]n, synthesized by the combination of L with
      ZnCl2, the Zn(II) centres are coordinated by two Cl atoms and two N atoms from
      two L ligands. [ZnCl2L]n forms one-dimensional P (plus) and M (minus) helical
      chains, where the L ligand has different directions of twist. The helical chains
      stack together via interchain pi-pi and C-H...pi interactions.

PMID- 24096496
TI  - (Hexafluorosilicato-kappa(2)F,F')bis(1,10-phenanthroline-kappa(2)N,N')zinc(II)
      methanol monosolvate.
AB  - The title compound, [Zn(SiF6)(C12H8N2)2].CH3OH, contains a neutral heteroleptic
      tris-chelate Zn(II) complex, viz. [Zn(SiF6)(phen)2] (phen is 1,10
      phenanthroline), exhibiting approximate molecular C2 point-group symmetry. The
      Zn(II) cation adopts a severely distorted octahedral coordination. As far as can
      be ascertained, the title complex represents the first structurally characterized
      example of a Zn(II) complex bearing a bidentate-bound hexafluorosilicate ligand.
      A density functional theory study of the isolated [Zn(SiF6)(phen)2] complex was
      undertaken to reveal the influence of crystal packing on the molecular structure
      of the complex. In the crystal structure, the methanol solvent molecule forms a
      hydrogen bond to one F atom of the hexafluorosilicate ligand. The hydrogen-bonded
      assemblies so formed are tightly packed in the crystal, as indicated by a high
      packing coefficient (74.1%). 

PMID- 24096497
TI  - Bis{MU-2,2'-[(butane-2,3
      diylidene)bis(azanylylidene)]dibenzenethiolato}dizinc(II)-dimethyl sulfoxide
      methanol (2/0.18/0.82).
AB  - The asymmetric unit in the crystal structure of the title compound,
      [Zn2(C16H14N2S2)2]2.0.18C2H6OS.0.82CH3OH, consists of two ordered bis{MU-2,2'
      [(butane-2,3-diylidene)bis(azanylylidene)]dibenzenethiolato}dizinc(II) molecules
      and a disordered solvent combination at the same location which refined to 18.1
      (7)% dimethyl sulfoxide and 81.9 (7)% methanol. The compound has a metallic
      cluster structure formed by the joining together of two zinc(II) complex
      molecules, forming a rhomboidal Zn2S2 arrangement. This complex was previously
      suggested on the basis of nonstructural evidence to be a monomer [Jadamus,
      Fernando & Freiser (1964). J. Am. Chem. Soc. 86, 3056-3059]. Each Zn(II) atom is
      five-coordinated and exhibits distorted trigonal bipyramidal geometry. The
      structure may be of interest with respect to zinc-thiolate bonds, the
      coordination chemistry of Schiff bases and the folding of proteins. The structure
      displays weak intermolecular C-H...S, C-H...O and C-H...N interactions, and
      contains a unique bonding arrangement of the ligands around the Zn2S2 rhomboid.

PMID- 24096498
TI  - Aluminium(III) amidinates formed from reactions of 'AlCl' with lithium
      amidinates.
AB  - The disproportionation of AlCl(THF)n (THF is tetrahydrofuran) in the presence of
      lithium amidinate species gives aluminium(III) amidinate complexes with partial
      or full chloride substitution. Three aluminium amidinate complexes formed during
      the reaction between aluminium monochloride and lithium amidinates are presented.
      The homoleptic complex tris(N,N'-diisopropylbenzimidamido)aluminium(III),
      [Al(C13H19N2)3] or Al{PhC[N(i-Pr)]2}3, (I), crystallizes from the same solution
      as the heteroleptic complex chloridobis(N,N'
      diisopropylbenzimidamido)aluminium(III), [Al(C13H19N2)2Cl] or Al{PhC[N(i
      Pr)]2}2Cl, (II). Both have two crystallographically independent molecules per
      asymmetric unit (Z' = 2) and (I) shows disorder in four of its N(i-Pr) groups.
      Changing the ligand substituent to the bulkier cyclohexyl allows the isolation of
      the partial THF solvate chloridobis(N,N'-dicyclohexylbenzimidamido)aluminium(III)
      tetrahydrofuran 0.675-solvate, [Al(C19H27N2)2Cl].0.675C4H8O or
      Al[PhC(NCy)2]2Cl.0.675THF, (III). Despite having a twofold rotation axis running
      through its Al and Cl atoms, (III) has a similar molecular structure to that of
      (II). 

PMID- 24096499
TI  - Poly[diaqua[MU4-4-(isonicotinamido)phthalato]nickel(II)] displaying an sra
      topology.
AB  - In the title compound, [Ni(C14H8N2O5)(H2O)2]n, the Ni(II) cation is six
      coordinate with a slightly distorted octahedral coordination geometry and the 4
      (isonicotinamido)phthalate ligand links the Ni(II) centres into a three
      dimensional structure with sra topology. The structure is also stabilized by N
      H...O hydrogen bonding between the uncoordinated amide groups of the ligand and
      extensive O-H...O hydrogen bonding between the two coordinated water molecules.
      The magnetic and thermal stability properties of the title compound are also
      discussed.

PMID- 24096500
TI  - A trimethylsulfonium salt with a novel polymeric cadmate anion.
AB  - The title salt, catena-poly[trimethylsulfonium [MU2-chlorido-di-MU2-thiocyanato
      cadmate(II)]] {(C3H9S)[CdCl(NCS)2]}n, consists of trimethylsulfonium cations
      sandwiched between layers of a two-dimensional polyanion. The Cd(II) centre
      displays a distorted octahedral environment coordinated by two bridging Cl atoms,
      two thiocyanate N atoms and two thiocyanate S atoms. The thiocyanate groups adopt
      the MU-1,3-coordination mode and bridge the Cd(II) centres into a one-dimensional
      zigzag chain extended along the [110] direction. The Cd(II) centres of the zigzag
      chains are crosslinked by bridging Cl atoms, forming a two-dimensional polyanion.
      The two-dimensional anions are linked to layers of trimethylsulfonium cations by
      weak intermolecular C-H...Cl hydrogen bonds, forming the three-dimensional
      structure.

PMID- 24096501
TI  - A three-dimensional polymeric potassium complex of 5-sulfonobenzene-1,2,4
      tricarboxylic acid: poly[MU-aqua-aqua-MU9-(2,4-dicarboxy-5-sulfonatobenzoato)
      dipotassium(I)].
AB  - The asymmetric unit in the structure of the title compound, [K2(C9H4O9S)(H2O)2]n,
      consists of two eight-coordinated K(I) cations, one 2,4-dicarboxy-5
      sulfonatobenzoate dianion (H2SBTC(2-)), one bridging water molecule and one
      terminal coordinated water molecule. One K(I) cation is coordinated by three
      carboxylate O atoms and three sulfonate O atoms from four H2SBTC(2-) ligands and
      by two bridging water molecules. The second K(I) cation is coordinated by four
      sulfonate O atoms and three carboxylate O atoms from five H2SBTC(2-) ligands and
      by one terminal coordinated water molecule. The K(I) cations are linked by
      sulfonate groups to give a one-dimensional inorganic chain with cage-like
      K4(SO3)2 repeat units. These one-dimensional chains are bridged by one of the
      carboxylic acid groups of the H2SBTC(2-) ligand to form a two-dimensional layer,
      and these layers are further linked by the remaining carboxylate groups and the
      benzene rings of the H2SBTC(2-) ligands to generate a three-dimensional
      framework. The compound displays a photoluminescent emission at 460 nm upon
      excitation at 358 nm. In addition, the thermal stability of the title compound
      has been studied. 

PMID- 24096502
TI  - The heterometallic cadmium-silver complex cis-bis[dicyanidoargentato(I)
      kappaN]bis(5,5'-dimethyl-2,2'-bipyridyl-kappa(2)N,N')cadmium(II) monohydrate.
AB  - In the title complex, [Ag2Cd(CN)4(C12H12N2)2].H2O or cis-[Cd{Ag(CN)2}2(5,5'
      dmbpy)2].H2O, where 5,5'-dmbpy is 5,5'-dimethyl-2,2'-bipyridyl, the asymmetric
      unit consists of a discrete neutral [Cd{Ag(CN)2}2(5,5'-dmbpy)2] unit and a
      solvent water molecule. The Cd(II) cation is coordinated by two bidentate chelate
      5,5'-dmbpy ligands and two monodentate [Ag(I)(CN)2](-) anions, which are in a cis
      arrangement around the Cd(II) cation, leading to an octahedral CdN6 geometry. The
      overall structure is stabilized by a combination of intermolecular hydrogen
      bonding, and Ag(I)...Ag(I) and pi-pi interactions, forming a three-dimensional
      supramolecular network.

PMID- 24096503
TI  - catena-Poly[[di-MU2-aqua-hexaaquabis(MU3-4-oxidopyridine-2,6
      dicarboxylato)trimanganese(II)] trihydrate]: a new one-dimensional coordination
      polymer based on a trinuclear Mn(II) complex of chelidamic acid.
AB  - 4-Hydroxypyridine-2,6-dicarboxylic acid (chelidamic acid, hypydc[H]H2) reacts
      with MnCl2.2H2O in the presence of piperazine in water to afford the title
      complex, {[Mn3(C7H2NO5)2(H2O)8].3H2O}n or {[Mn3(hypydc)2(H2O)8].3H2O}n. This
      compound is a one-dimensional coordination polymer, with the twofold symmetric
      repeat unit containing three metal centres. Two different coordination geometries
      are observed for the two independent Mn(II) metal centres, viz. a distorted
      pentagonal bipyramid and a distorted octahedron. The 4-oxidopyridine-2,6
      dicarboxylate anions and two of the water molecules act as bridging ligands. The
      zigzag-like geometry of the coordination polymer is stabilized by hydrogen bonds.
      O-H...O and C-H...O hydrogen bonds and water clusters consolidate the three
      dimensional network structure.

PMID- 24096504
TI  - Zigzag polymer chains in catena-poly[[[triaqua(isobutyrato-kappaO)magnesium(II)]
      MU-isobutyrato-kappa(2)O:O'] monohydrate].
AB  - The structure of the title compound, {[Mg(C4H7O2)2(H2O)3].H2O}n, features one
      dimensional ...(MU2-ib)Mg(MU2-ib)Mg... zigzag chains (ib is isobutyrate) parallel
      to the c axis. The octahedral Mg environment is completed by three fac-oriented
      terminal water ligands, as well as one further monodentate end-on coordinated ib
      ligand. In the crystal structure, the hydrophobic ib groups are all oriented
      within one half of the coordination perimeter of each chain, whereas the water
      ligands, together with hydrogen-bonded noncoordinated solvent water molecules,
      define the other half. Along the a axis, neighbouring strands are oriented so
      that both the hydrophilic and hydrophobic sides are adjacent to each other. This
      results in an extensive hydrogen-bonding network within the hydrophilic areas,
      also involving an additional solvent water molecule per formula unit. There are
      van der Waals contacts between the aliphatic isopropyl groups of the hydrophobic
      areas.

PMID- 24096505
TI  - A one-dimensional cadmium metal-organic chain based on a [Cd4(COO)4] secondary
      building unit and a flexible dicarboxylic acid ligand.
AB  - An infinite one-dimensional cadmium metal-organic chain, namely catena
      poly[aquabis(MU3-2,2'-{[1,2
      phenylenebis(methylene)]bis(sulfanediyl)}dibenzoato)dicadmium(II)],
      [Cd2(C22H16O4S2)2(H2O)]n, was synthesized by solvothermal reaction of
      Cd(NO3)2.4H2O and 2,2'-{[1,2-phenylenebis(methylene)]bis(sulfanediyl)}dibenzoic
      acid (H2L). The Cd(II) centres have six-coordinate CdS2O4 and CdSO5 geometries.
      Due to the flexible -CH2-S- arms, the L(2-) ligand adopts both syn and anti
      conformations. Four Cd(II) cations are linked by two syn L(2-) ligands to form a
      centrosymmetric planar tetranuclear Cd(II) core, which is further extended
      through bonding to the anti L(2-) ligands to form a one-dimensional metal-organic
      chain. Adjacent one-dimensional chains are connected by C-H...pi interactions and
      nonclassical C-H...O hydrogen bonds to form the resultant three-dimensional
      supramolecular framework.

PMID- 24096506
TI  - 2-Amino-5-iodopyridinium bromide hemihydrate and 2-amino-5-iodopyridinium
      chloride monohydrate.
AB  - The hydrobromide and hydrochloride salts of 2-amino-5-iodopyridine were prepared
      from aqueous solutions. The hydrobromide salt, C5H6IN2(+).Br(-).0.5H2O,
      crystallizes as a hemihydrate, and exhibits hydrogen bonding and pi-stacking
      which stabilize the crystal structure. The hydrochloride salt, C5H6IN2(+).Cl(
      ).H2O.0.375HCl, crystallized as the hydrate and exhibits similar hydrogen bonding
      and pi-stacking in the lattice. The most interesting feature of the hydrochloride
      salt is the presence of an additional fractional HCl molecule which introduces
      disorder in the location of the water molecule. The additional proton from the
      fractional HCl molecule is accounted for by the presence of a partial hydronium
      ion on one of the water sites. 

PMID- 24096507
TI  - Four related diethyl [(arylamino)(4-ethynylphenyl)methyl]phosphonates.
AB  - Crystal structures are reported for four related diethyl [(arylamino)(4
      ethynylphenyl)lmethyl]phosphonate derivatives, namely diethyl [(4-bromoanilino)(4
      ethynylphenyl)methyl]phosphonate, C19H21BrNO3P, (I), diethyl ((4-chloro-2
      methylanilino){4-[2-(trimethylsilyl)ethynyl]phenyl}methyl)phosphonate,
      C23H31ClNO3PSi, (II), diethyl ((4-fluoroanilino){4-[2
      (trimethylsilyl)ethynyl]phenyl}methyl)phosphonate, C22H29FNO3PSi, (III), and
      diethyl [(4-ethynylphenyl)(naphthalen-2-ylamino)methyl]phosphonate, C23H24NO3P,
      (IV). The conformation of the anilinobenzyl group is very similar in all four
      compounds. The P-C bond has an approximately staggered conformation, with the
      aniline and ethynylphenyl groups in gauche positions with respect to the P=O
      double bond. The two six-membered rings are almost perpendicular. The sums of the
      valence angles about the N atoms vary from 344 (2) to 351 (2) degrees . In the
      crystal structures, molecules of (I), (III) and (IV) are arranged as
      centrosymmetric or pseudocentrosymmetric dimers connected by two N-H...O=P
      hydrogen bonds. The molecules of (II) are arranged as centrosymmetric dimers
      connected by C(methyl)-H...O=P hydrogen bonds. The N-H bond of (II) is not
      involved in hydrogen bonding.

PMID- 24096509
TI  - C5 and C7 intramolecular hydrogen bonds stabilize the structure of N-pyrazinoyl
      gabapentin (Pyr-Gpn-OH).
AB  - 2-{1-[(Pyrazin-2-ylformamido)methyl]cyclohexyl}acetic acid (Pyr-Gpn-OH),
      C14H19N3O3, is an N-protected derivative of gabapentin (Gpn). The compound
      crystallizes in the triclinic space group P1 and the molecular conformation is
      stabilized by intramolecular five- (C5) and seven-membered (C7) hydrogen-bonded
      rings. The packing of the molecules reveals intermolecular O-H...O and C-H...N
      hydrogen bonds, together with pi-pi interactions.

PMID- 24096508
TI  - Solvent-mediated pseudo-quadruple hydrogen-bond motifs in three lamotrigine
      carboxylic acid complexes.
AB  - Lamotrigine, an antiepileptic drug, has been complexed with three aromatic
      carboxylic acids. All three compounds crystallize with the inclusion of N,N
      dimethylformamide (DMF) solvent, viz. lamotriginium [3,5-diamino-6-(2,3
      dichlorophenyl)-1,2,4-triazin-2-ium] 4-iodobenzoate N,N-dimethylformamide
      monosolvate, C9H8Cl2N5(+).C7H4IO2(-).C3H7NO, (I), lamotriginium 4-methylbenzoate
      N,N-dimethylformamide monosolvate, C9H7Cl2N5(+).C8H8O2(-).C3H7NO, (II), and
      lamotriginium 3,5-dinitro-2-hydroxybenzoate N,N-dimethylformamide monosolvate,
      C9H8Cl2N5(+).C7H3N2O7(-).C3H7NO, (III). In all three structures, proton transfer
      takes place from the acid to the lamotrigine molecule. However, in (I) and (II),
      the acidic H atom is disordered over two sites and there is only partial transfer
      of the H atom from O to N. In (III), the corresponding H atom is ordered and
      complete proton transfer has occurred. Lamotrigine-lamotrigine, lamotrigine-acid
      and lamotrigine-solvent interactions are observed in all three structures and
      they thereby exhibit isostructurality. The DMF solvent extends the lamotrigine
      lamotrigine dimers into a pseudo-quadruple hydrogen-bonding motif. 

PMID- 24096510
TI  - 1-Carboxymethyl-3-methyl-1H-imidazol-3-ium chloride 2-(3-methyl-1H-imidazol-3-ium
      1-yl)acetate monohydrate: a crystal stabilized by imidazolium zwitterions.
AB  - The title compound, C6H9N2O2(+).Cl(-).C6H8N2O2.H2O, contains one 2-(3-methyl-1H
      imidazol-3-ium-1-yl)acetate inner salt molecule, one 1-carboxymethyl-3-methyl-1H
      imidazol-3-ium cation, one chloride ion and one water molecule. In the extended
      structure, chloride anions and water molecules are linked via O-H...Cl hydrogen
      bonds, forming an infinite one-dimensional chain. The chloride anions are also
      linked by two weak C-H...Cl interactions to neighbouring methylene groups and
      imidazole rings. Two imidazolium moieties form a homoconjugated cation through a
      strong and asymmetric O-H...O hydrogen bond of 2.472 (2) A. The IR spectrum shows
      a continuous D-type absorption in the region below 1300 cm(-1) and is different
      to that of 1-carboxymethyl-3-methylimidazolium chloride [Xuan, Wang & Xue (2012).
      Spectrochim. Acta Part A, 96, 436-443].

PMID- 24096511
TI  - Two seven-membered heterocycles with 1,2-diaza ring N atoms: 3,5,7-triphenyl-1,2
      diazacyclohepta-1(7),2-diene and 3,7-bis(2-hydroxyphenyl)-5-phenyl-1,2
      diazacyclohepta-1(7),2-diene.
AB  - The title compounds, 3,5,7-triphenyl-1,2-diazacyclohepta-1(7),2-diene, C23H20N2,
      (I), and 3,7-bis(2-hydroxyphenyl)-5-phenyl-1,2-diazacyclohepta-1(7),2-diene,
      C23H20N2O2, (II), constitute the first structurally characterized examples of
      seven-membered heterocycles with 1,2-diaza ring N atoms. Compound (I)
      crystallizes in the space group P1, with two independent molecules in the
      asymmetric unit that differ in the conformation of one of the phenyl rings, while
      (II) crystallizes in the space group C2/c. The C5N2 ring in each of (I) and (II)
      adopts a twist-boat conformation. Compound (I) exhibits neither C-H...pi
      interactions nor pi-pi stacking interactions, whereas (II) shows both
      intramolecular O-H...N hydrogen bonds and a C-H...pi interaction that joins the
      molecules into an infinite chain in the [010] direction.

PMID- 24096512
TI  - New rac-XP(O)(OC6H5)(NHC6H4-p-CH3) [X = N(CH3)(cyclo-C6H11) and NH(C3H5)] and rac
      (C6H5CH2NH)P(O)(OC6H5)(NH-cyclo-C6H11) mixed-amide phosphinates.
AB  - The mixed-amide phosphinates, rac-phenyl (N-methylcyclohexylamido)(p
      tolylamido)phosphinate, C20H27N2O2P, (I), and rac-phenyl (allylamido)(p
      tolylamido)phosphinate, C16H19N2O2P, (II), were synthesized from the racemic
      phosphorus-chlorine compound (R,S)-(Cl)P(O)(OC6H5)(NHC6H4-p-CH3). Furthermore,
      the phosphorus-chlorine compound ClP(O)(OC6H5)(NH-cyclo-C6H11) was synthesized
      for the first time and used for the synthesis of rac-phenyl
      (benzylamido)(cyclohexylamido)phosphinate, C19H25N2O2P, (III). The strategies for
      the synthesis of racemic mixed-amide phosphinates are discussed. The P atom in
      each compound is in a distorted tetrahedral (N(1))P(=O)(O)(N(2)) environment. In
      (I) and (II), the p-tolylamido substituent makes a longer P-N bond than those
      involving the N-methylcyclohexylamido and allylamido substituents. In (III), the
      differences between the P-N bond lengths involving the cyclohexylamido and
      benzylamido substituents are not significant. In all three structures, the
      phosphoryl O atom takes part with the N-H unit in hydrogen-bonding interactions,
      viz. an N-H...O=P hydrogen bond for (I) and (N-H)(N-H)...O=P hydrogen bonds for
      (II) and (III), building linear arrangements along [001] for (I) and along [010]
      for (III), and a ladder arrangement along [100] for (II).

PMID- 24096513
TI  - Zolmitriptan oxalate and zolmitriptan camphorsulfonate: the first structural
      study of salt complexes of the antimigraine drug zolmitriptan.
AB  - Zolmitriptan hydrogen oxalate [(S)-dimethyl(2-{5-[(2-oxo-1,3-oxazolidin-4
      yl)methyl]-1H-indol-3-yl}ethyl)azanium hydrogen oxalate], C16H22N3O2(+).C2HO4(-),
      (I), and zolmitriptan camphorsulfonate [(S)-dimethyl(2-{5-[(2-oxo-1,3-oxazolidin
      4-yl)methyl]-1H-indol-3-yl}ethyl)azanium (S,R)-{2-hydroxy-7,7
      dimethylbicyclo[2.2.1]heptan-1-yl}methanesulfonate], C16H22N3O2(+).C10H15O4S(-),
      (II), are the first reported salt complexes of the antimigraine drug
      zolmitriptan. Compound (I) crystallizes in the space group P2(1) with two
      molecules of protonated zolmitriptan and two oxalate monoanions in the asymmetric
      unit, while compound (II) crystallizes in the space group P2(1)2(1)2(1) with one
      protonated zolmitriptan molecule and one camphorsulfonate anion in the asymmetric
      unit. The orientations of the ethylamine side chain and the oxazolidinone ring
      with respect to the indole ring of the zolmitriptan cation are different for (I)
      and (II). In (I), they are oriented in opposite directions and the molecule
      adopts a step-like appearance, while in (II) the corresponding side chains are
      folded in the same direction, giving the molecule a cup-like appearance. The
      zolmitriptan molecules of (I) form an R2(2)(8) dimer, while in (II) they form a
      helical chain with a C(11) motif. The oxalate monoanions of (I) interact with the
      zolmitriptan cations and extend the dimer into a three-dimensional hydrogen
      bonded network. In (II), the camphorsulfonate anion forms an R2(2)(15) ring motif
      with the zolmitriptan cation.

PMID- 24096514
TI  - Three-dimensional hydrogen-bonded structures in the hydrated proton-transfer
      salts of isonipecotamide with the dicarboxylic oxalic and adipic acid homologues.
AB  - The structures of the 1:1 hydrated proton-transfer compounds of isonipecotamide
      (piperidine-4-carboxamide) with oxalic acid, 4-carbamoylpiperidinium hydrogen
      oxalate dihydrate, C6H13N2O(+).C2HO4(-).2H2O, (I), and with adipic acid, bis(4
      carbamoylpiperidinium) adipate dihydrate, 2C6H13N2O(+).C6H8O4(2-).2H2O, (II), are
      three-dimensional hydrogen-bonded constructs involving several different types of
      enlarged water-bridged cyclic associations. In the structure of (I), the oxalate
      monoanions give head-to-tail carboxylic acid O-H...O(carboxyl) hydrogen-bonding
      interactions, forming C(5) chain substructures which extend along a. The
      isonipecotamide cations also give parallel chain substructures through amide N
      H...O hydrogen bonds, the chains being linked across b and down c by alternating
      water bridges involving both carboxyl and amide O-atom acceptors and amide and
      piperidinium N-H...O(carboxyl) hydrogen bonds, generating cyclic R4(3)(10) and
      R3(2)(11) motifs. In the structure of (II), the asymmetric unit comprises a
      piperidinium cation, half an adipate dianion, which lies across a
      crystallographic inversion centre, and a solvent water molecule. In the crystal
      structure, the two inversion-related cations are interlinked through the two
      water molecules, which act as acceptors in dual amide N-H...O(water) hydrogen
      bonds, to give a cyclic R4(2)(8) association which is conjoined with an R4(4)(12)
      motif. Further N-H...O(water), water O-H...O(amide) and piperidinium N
      H...O(carboxyl) hydrogen bonds give the overall three-dimensional structure. The
      structures reported here further demonstrate the utility of the isonipecotamide
      cation as a synthon for the generation of stable hydrogen-bonded structures. The
      presence of solvent water molecules in these structures is largely responsible
      for the non-occurrence of the common hydrogen-bonded amide-amide dimer, promoting
      instead various expanded cyclic hydrogen-bonding motifs.

PMID- 24096515
TI  - The six-membered-ring azomethine N-((E)-{5-[(E)-(pyridin-3
      ylimino)methyl]thiophen-2-yl}methylidene)pyridin-3-amine.
AB  - The title compound, C16H12N4S, forms a three-dimensional layered network
      structure via intermolecular hydrogen bonding and pi-stacking. The azomethine
      molecule adopts the thermodynamically stable E regioisomer and the pyridine
      substituents are antiperiplanar. The mean planes of the pyridine rings and the
      azomethine group to which they are connected are twisted by 27.27 (5) and 33.60
      (5) degrees . The electrochemical energy gap of 2.3 eV based on the HOMO-LUMO
      energy difference is in agreement with the spectroscopically derived value. 

PMID- 24096516
TI  - Dimers linked by type-I C-F...F-C contacts in (Z)-3-methyl-4-[2-(4
      methylphenyl)hydrazinylidene]-1-(pentafluorophenyl)-1H-pyrazol-5(4H)-one.
AB  - The title compound, C17H11F5N4O, is described and compared with two closely
      related analogues in the literature. There are two independent molecules in the
      asymmetric unit, linked by N-H...O hydrogen bonds and pi-pi interactions into
      dimeric entities, presenting a noticeable noncrystallographic C2 symmetry. These
      dimers are in turn linked by a medium-strength type-I C-F...F-C interaction into
      elongated tetramers. Much weaker C-H...F contacts link the tetramers into broad
      two-dimensional substructures parallel to (101).

PMID- 24096518
TI  - Gender identity in informal care: impact on health in Spanish caregivers.
AB  - We examined the influence of gender identity on men's and women's perceptions of
      assuming the caregiver role to identify different coping strategies and the
      effects on caregiver health and quality of life. The study, performed in
      Andalusia, Spain, was based on a sociological analysis of the narratives produced
      during semistructured interviews with primary informal caregivers (16 men and 16
      women) of different profiles. We observed a cultural assumption that women should
      assume the caregiver role and found that women shouldered the bulk of caregiving
      responsibilities and did not usually seek support. This might explain the high
      prevalence of chronic health disorders, stress, anxiety, depression, neglect of
      health, and social isolation we observed among women caregivers. Because the
      caregiver role was not socially imposed on men in our setting, men caregivers
      adopted a flexible attitude and tended to seek external support before their
      health and quality of life were seriously affected. 

PMID- 24096519
TI  - Body composition phenotypes and carotid intima-media thickness in 11-13-year-old
      children.
AB  - Early detection of impairment in vascular structure is an important clinical
      pursuit. However, it is unknown which measure of body composition best predicts
      vascular wall changes. We assess the differences in body composition among intima
      media thickness (IMT) tertiles and determined which measures of body composition
      are associated with IMT in 385 children aged 11-13 years (196 girls). In this
      cross-sectional study, body mass index (BMI), waist circumference (WC), body fat
      mass (BFM), and trunk fat mass (TFM) from dual-energy radiographic absorptiometry
      and IMT through high-resolution ultrasonography were collected. Differences in
      body composition measures among IMT tertiles [low IMT (LIMT), <= 0.46 mm; middle
      IMT, 0.46-0.53 mm; higher IMT (HIMT), >=0.53 mm] were assessed with ANOVA/ANCOVA
      after categorization. Regression analysis was used to assess the relationships
      between body composition and IMT. The groups were similar for sex, age, and
      maturity (p > 0.05). As compared with LIMT group, subjects with HIMT had higher
      mean values of BMI, BFM, TFM, and WC (p < 0.05). Significant differences were
      found for WC even when controlling for BMI (p < 0.05). Combining all subjects,
      IMT was significantly correlated to BMI, BFM, TFM, and WC (p < 0.05). In multiple
      regression, WC was the only predictor of IMT (beta = 0.22, p < 0.001).
      CONCLUSION: Differences exist in body composition variables among IMT tertiles.
      In the overall model, WC was the only obesity-related predictor of increased IMT
      in 11-13-year-old children.

PMID- 24096520
TI  - Demographic characteristics and metabolic risk factors in Croatian children with
      urolithiasis.
AB  - The aim of this study was to assess demographic data, clinical presentation,
      metabolic features, and treatment in 76 children with urolithiasis presented from
      2002 to 2011. Urolithiasis is responsible for 2.5/1,000 pediatric
      hospitalizations, with new cases diagnosed in 1.1/1,000 admissions. From the
      observed period, two-fold rise of incidence rate was observed. Compiling the data
      from other pediatric institutions in our country, we estimated present overall
      incidence rate in Croatia as 6.5/100,000 children under 18 years. There were 41
      boys and 35 girls (ratio 1.17:1). The mean age at diagnosis was 9.7 (range 0.8
      16) years and follow-up duration was 5.3 (range 1.8-10) years. Renal colic (75.0
      %) and hematuria (57.89 %) were the main symptoms. In 65.78 % of children, stones
      were unilateral. Stones were located in kidney in 52.63 %, in the ureter in 26.32
      %, and in bladder in 6.58 % cases. Stone analysis showed calcium oxalate in 75.0
      % of the cases. Associated urinary tract abnormalities were found in 19.73 %
      children. Most common metabolic disturbances were hypercalciuria (47.37 %) and
      idiopathic or mild hyperoxaluria (18.42 %). Urine saturation (EQUIL2) was
      elevated in 61.84 % cases. Spontaneous stone evacuation occurred in 51.21 %
      children. Extracorporeal shock wave lithotripsy, surgical evacuation, and
      endoscopic removal of calculi were performed in 21.0, 6.58, and 5.26 % of cases,
      respectively. Follow-up conservative therapy, consisting of fluid/diet
      recommendations and additional potassium citrate and/or chlorothiazide in
      children with increased risk, was sufficient for stone recurrence prevention in
      92.1 % of children. In conclusion, the study gave insight in epidemiology and
      metabolic disturbances of urinary stone disease in Croatian children.

PMID- 24096521
TI  - Neurological involvement in incontinentia pigmenti.

PMID- 24096522
TI  - Corneal microcysts.

PMID- 24096523
TI  - Non-pheochromocytoma (PCC)/paraganglioma (PGL) tumors in patients with succinate
      dehydrogenase-related PCC-PGL syndromes: a clinicopathological and molecular
      analysis.
AB  - OBJECTIVE: Although the succinate dehydrogenase (SDH)-related tumor spectrum has
      been recently expanded, there are only rare reports of non
      pheochromocytoma/paraganglioma tumors in SDHx-mutated patients. Therefore,
      questions still remain unresolved concerning the aforementioned tumors with
      regard to their pathogenesis, clinicopathological phenotype, and even causal
      relatedness to SDHx mutations. Absence of SDHB expression in tumors derived from
      tissues susceptible to SDH deficiency is not fully elucidated. DESIGN AND
      METHODS: Three unrelated SDHD patients, two with pituitary adenoma (PA) and one
      with papillary thyroid carcinoma (PTC), and three SDHB patients affected by renal
      cell carcinomas (RCCs) were identified from four European centers. SDHA/SDHB
      immunohistochemistry (IHC), SDHx mutation analysis, and loss of heterozygosity
      analysis of the involved SDHx gene were performed on all tumors. A cohort of 348
      tumors of unknown SDHx mutational status, including renal tumors, PTCs, PAs,
      neuroblastic tumors, seminomas, and adenomatoid tumors, was investigated by SDHB
      IHC. RESULTS: Of the six index patients, all RCCs and one PA displayed SDHB
      immunonegativity in contrast to the other PA and PTC. All immunonegative tumors
      demonstrated loss of the WT allele, indicating bi-allelic inactivation of the
      germline mutated gene. Of 348 tumors, one clear cell RCC exhibited partial loss
      of SDHB expression. CONCLUSIONS: These findings strengthen the etiological
      association of SDHx genes with pituitary neoplasia and provide evidence against a
      link between PTC and SDHx mutations. Somatic deletions seem to constitute the
      second hit in SDHB-related renal neoplasia, while SDHx alterations do not appear
      to be primary drivers in sporadic tumorigenesis from tissues affected by SDH
      deficiency.

PMID- 24096524
TI  - Calciphylaxis is a cutaneous process without involvement of internal organs in a
      retrospective study of postmortem findings in three patients.
AB  - Calciphylaxis causes calcification, thrombosis, cutaneous ischemia, and necrosis
      in the skin and subcutaneous tissue. It is unclear to what extent it involves
      other organs. To identify whether other organs are affected we reviewed pathology
      reports of patients with calciphylaxis who underwent autopsy at Mayo Clinic,
      Rochester, Minnesota, between January 1, 1970, and December 31, 2011. Three
      patients were identified: two patients had a diagnosis of end-stage renal disease
      secondary to diabetes mellitus before the diagnosis of calciphylaxis; the third
      patient had calciphylaxis associated with metastatic cholangiocarcinoma without
      end-stage renal disease. Autopsy reports showed that despite evidence of vessel
      calcification elsewhere, there was no evidence of calciphylaxis in other organs.
      All patients had histopathologic evidence of cardiovascular calcification, and
      atherosclerosis of coronary arteries and aorta. Calcification of pancreatic
      vessels and renal vessels was also noted. In this study population, calciphylaxis
      was a cutaneous process alone. 

PMID- 24096517
TI  - The orphan nuclear receptors at their 25-year reunion.
AB  - The nuclear receptor superfamily includes many receptors, identified based on
      their similarity to steroid hormone receptors but without a known ligand. The
      study of how these receptors are diversely regulated to interact with genomic
      regions to control a plethora of biological processes has provided critical
      insight into development, physiology, and the molecular pathology of disease.
      Here we provide a compendium of these so-called orphan receptors and focus on
      what has been learned about their modes of action, physiological functions, and
      therapeutic promise. 

PMID- 24096525
TI  - Preventive cardiovascular care for older people: fundamental for healthy ageing?

PMID- 24096527
TI  - Cold-active xylanase produced by fungi associated with Antarctic marine sponges.
AB  - Despite their potential biotechnological applications, cold-active xylanolytic
      enzymes have been poorly studied. In this work, 38 fungi isolated from marine
      sponges collected in King George Island, Antarctica, were screened as new sources
      of cold-active xylanases. All of them showed xylanase activity at 15 and 23 
      degrees C in semiquantitative plate assays. One of these isolates, Cladosporium
      sp., showed the highest activity and was characterized in detail. Cladosporium
      sp. showed higher xylanolytic activity when grown on beechwood or birchwood xylan
      and wheat bran, but wheat straw and oat bran were not so good inducers of this
      activity. The optimal pH for xylanase activity was 6.0, although pH stability was
      slightly wider (pH 5-7). On the other hand, Cladosporium sp. showed high xylanase
      activity at low temperatures and very low thermal stability. Interestingly,
      thermal stability was even lower after culture media were removed and replaced by
      buffer, suggesting that low molecular component(s) of the culture media could be
      important in the stabilization of cold-active xylanase activity. To the best of
      our knowledge, this study is the first report on extracellular xylanase
      production by fungi associated with Antarctic marine sponges.

PMID- 24096526
TI  - Geochemical behavior of metals and metalloids in an estuary affected by acid mine
      drainage (AMD).
AB  - The Tinto and Odiel rivers in southwest Spain drain the world's largest sulfide
      mineral formation: the Iberian Pyrite Belt which has been worked since 2,500 BC.
      The Tinto and Odiel estuarine zones include both an extensive area of salt marsh
      and an intensively industrialized urban area. As a consequence of pyrite
      oxidation, the Tinto and Odiel rivers are strongly acidic (pH < 3) with unusually
      high and quite variable metal concentrations. In this study, seasonally varying
      concentrations of dissolved major and trace elements were determined in the acid
      mine drainage affected estuary of the Ria de Huelva. During estuarine mixing, ore
      derived metal concentrations exhibit excellent correlations with pH as the main
      controlling parameter. As pH increases, concentrations of dissolved ore
      associated elements are attenuated, and this process is enhanced during the
      summer months. The decrease in Fe and Al concentrations ranged from 80 to 100 %
      as these elements are converted from dissolved to sediment-associated forms in
      the estuary. Coprecipitation/adsorption processes also removed between 60 and 90
      % of the originally dissolved Co, Cu, Mn, Pb, Zn, and Th; however, Cd and Ni
      exhibited a greater propensity to remain in solution, with an average removal of
      approximately 60 %. On the other hand, As and U exhibited a different behavior;
      it is likely that these elements remain in dissolved forms because of the
      formation of U carbonates and soluble As species. Concentrations of As remain at
      elevated levels in the outer estuary (average = 48 MUg L(-1)) which exceeds
      concentrations present in the Tinto River. Nevertheless, the estuary has recently
      witnessed improvements in water quality, as compared to results of several
      previous studies reported in the 1990s.

PMID- 24096528
TI  - Minimal invasive extrathoracic presternal compression using a metal bar for
      correction of pectus carinatum.
AB  - BACKGROUND: This report presents early results of surgical experience of minimal
      invasive extrathoracic presternal compression using a metal bar for correction of
      the pectus carinatum. METHODS: From February 2008 to February 2012, 15 patients
      with combined pectus carinatum and pectus excavatum underwent minimal invasive
      extrathoracic presternal compression using a metal bar for correction of pectus
      carinatum and Nuss operation for pectus excavatum. After 2 years, bar removal was
      done in all patients. In this paper, we focused on pectus carinatum repair. The
      effects and complications of the minimally invasive extrathoracic presternal
      compression using a metal bar for correction of pectus carinatum were reviewed.
      RESULTS: The median age was 15.7 years. The mean operation time for pectus
      carinatum with pectus excavatum was 122 min. The median length of hospitalization
      was 6 days. The Haller pectus index of pectus carinatum was 2.93 +/- 0.36 pre
      operatively and this was increased to 3.33 +/- 0.61 post-operatively. There were
      no special complications. The degree of satisfaction of pectus carinatum
      correction was 3.75 +/- 0.46 (range 1-4). CONCLUSION: Our results were favorable
      in spite of the small number of cases and short follow-up, and our modified
      technique of pectus carinatum was easy and simple. However, long-term follow-up
      is needed to accurately evaluate the effects of this surgery in many cases.

PMID- 24096529
TI  - Invited commentary: Fostering resilience among Native American youth through
      therapeutic intervention.
AB  - This article offers a comprehensive overview and understanding of the needs of
      Native American Youth for researchers, educators, and practitioners based on
      current research and practice. Strengths and protective factors are discussed in
      terms of Native strengths in context, the strengths and resilience of Native
      ways, Indigenous ways of knowing, the relationship between cultural identity and
      the tribal nation, the importance of family, the roles of the wisdom keepers,
      spiritual ways, and communication styles. Contextual influences are explored in
      terms of the relationship between history and healing from intergenerational
      grief and trauma, the influence of acculturation, as well as current social,
      economic, and political issues that affect Native youth. Implications for
      research and therapeutic intervention are explored in terms of healing from
      historical trauma and oppression. The authors offer an overview of common
      presenting issues and recommendations, practical tribally-specific interventions,
      and reflections on what it means to work from a social justice and
      client/community advocacy perspective with a focus on providing effective
      therapeutic, culturally-based interventions with Native children and adolescents
      that promote resilience and foster positive development with this population. 

PMID- 24096530
TI  - Friend affiliations and school adjustment among Mexican-American adolescents: the
      moderating role of peer and parent support.
AB  - Studies examining friendships among Mexican-American adolescents have largely
      focused on their potentially negative influence. The current study examined the
      extent to which deviant and achievement-oriented friend affiliations are
      associated with Mexican-American adolescents' school adjustment and also tested
      whether support from friends and parents moderates these associations. High
      school students (N = 412; 49 % male) completed questionnaires and daily diaries;
      primary caregivers also completed a questionnaire. Although results revealed few
      direct associations between friend affiliations and school adjustment, several
      moderations emerged. In general, the influence of friends' affiliation was
      strongest when support from friends was high and parental support was low. The
      findings suggest that only examining links between friend affiliations and school
      outcomes does not fully capture how friends promote or hinder school adjustment. 

PMID- 24096531
TI  - Development of an attached-growth process for the on-site bioremediation of an
      aquifer polluted by chlorinated solvents.
AB  - A procedure for the design of an aerobic cometabolic process for the on-site
      degradation of chlorinated solvents in a packed bed reactor was developed using
      groundwater from an aquifer contaminated by trichloroethylene (TCE) and 1,1,2,2
      tetrachloroethane (TeCA). The work led to the selection of butane among five
      tested growth substrates, and to the development and characterization from the
      site's indigenous biomass of a suspended-cell consortium capable to degrade TCE
      (first order constant: 96 L gprotein(-1) day(-1) at 30  degrees C and 4.3 L
      gprotein(-1) day(-1) at 15  degrees C) with a 90 % mineralization of the organic
      chlorine. The consortium immobilization had strong effects on the butane and TCE
      degradation rates. The microbial community structure was slightly changed by a
      temperature shift from 30 to 15  degrees C, but remarkably affected by biomass
      adhesion. Given the higher TCE normalized degradation rate (0.59 day(-1) at 15 
      degrees C) and attached biomass concentration (0.13 gprotein Lbioreactor(-1) at
      15  degrees C) attained, the porous ceramic carrier Biomax was selected as the
      best option for the packed bed reactor process. The low TeCA degradation rate
      exhibited by the developed consortium suggested the inclusion of a chemical pre
      treatment based on the TeCA to TCE conversion via beta-elimination, a very fast
      reaction at alkaline pH. To the best of the authors' knowledge, this represents
      the first attempt to develop a procedure for the development of a packed bed
      reactor process for the aerobic cometabolism of chlorinated solvents.

PMID- 24096532
TI  - Soybean fermentation with Bacillus licheniformis increases insulin sensitizing
      and insulinotropic activity.
AB  - Traditionally fermented soybeans (chungkookjang; TFC) may have potent anti
      diabetic activity, depending on the ambient microorganisms and conditions. We
      hypothesized that one of the major Bacillus species in TFC contributes to the
      anti-diabetic activity and could be used to standardize a highly functional TFC.
      We tested the hypothesis by using cell-based studies to evaluate insulin
      sensitizing and insulinotropic action of chungkookjangs fermented with various
      Bacillus spp. and fermentation periods. The 70% methanol and water extracts of
      chungkookjang fermented with Bacillus licheniformis (BL) for 48 h contained
      similar profiles of isoflavonoids and peptides to methanol and water extracts of
      TFC with potent anti-diabetic activity. Water extracts (mainly containing
      peptides) of TFC and BL fermented for 48 h and 72 h had a better insulin
      sensitizing action via activating peroxisome proliferator-activated receptor
      gamma (PPAR-gamma) and increased the expression of PPAR-gamma in 3T3-L1
      adipocytes better than unfermented cooked soybeans (CSB). The 70% methanol
      extracts (predominantly isoflavone aglycones) of BL fermented for 48 h and 72 h
      improved glucose-stimulated insulin secretion and protected beta-cell viability
      better than CSB in insulinoma cells, and the improvement by BL was similar to
      TFC. In conclusion, the BL water extract fermented for 48 h exhibited equal
      insulin sensitization as TFC and BL methanol extract exerted similar
      insulinotropic actions to those of TFC. B. licheniformis may be one of the major
      microorganisms responsible for anti-diabetic actions of chungkookjang. It is
      important to make chungkookjang that retains the anti-diabetic properties of the
      most efficacious traditional chungkookjang using a standardized method. 

PMID- 24096534
TI  - Effects of acute withdrawal on ethanol-induced conditioned place preference in
      DBA/2J mice.
AB  - RATIONALE: Reexposure to ethanol during acute withdrawal might facilitate the
      transition to alcoholism by enhancing the rewarding effect of ethanol. OBJECTIVE:
      The conditioned place preference (CPP) procedure was used to test whether ethanol
      reward is enhanced during acute withdrawal. METHODS: DBA/2J mice were exposed to
      an unbiased one-compartment CPP procedure. Ethanol (0.75, 1.0, or 1.5 g/kg IP)
      was paired with a distinctive floor cue (CS+), whereas saline was paired with a
      different floor cue (CS-). The withdrawal (W) group received CS+ trials during
      acute withdrawal produced by a large dose of ethanol (4 g/kg) given 8 h before
      each trial. The no-withdrawal (NW) group did not experience acute withdrawal
      during conditioning trials but was matched for acute withdrawal experience. Floor
      preference was tested in the absence of ethanol or acute withdrawal. RESULTS: All
      groups eventually showed a dose-dependent preference for the ethanol-paired cue,
      but development of CPP was generally more rapid and stable in the W groups than
      in the NW groups. Acute withdrawal suppressed the normal activating effect of
      ethanol during CS+ trials, but there were no group differences in test activity.
      CONCLUSIONS: Acute withdrawal enhanced ethanol's rewarding effect as indexed by
      CPP. Since this effect depended on ethanol exposure during acute withdrawal, the
      enhancement of ethanol reward was likely mediated by the alleviation of acute
      withdrawal, i.e., negative reinforcement. Enhancement of ethanol reward during
      acute withdrawal may be a key component in the shift from episodic to chronic
      ethanol consumption that characterizes alcoholism.

PMID- 24096533
TI  - Biomarkers in autism spectrum disorder: the old and the new.
AB  - RATIONALE: Autism spectrum disorder (ASD) is a complex heterogeneous
      neurodevelopmental disorder with onset during early childhood and typically a
      life-long course. The majority of ASD cases stems from complex, 'multiple-hit',
      oligogenic/polygenic underpinnings involving several loci and possibly gene
      environment interactions. These multiple layers of complexity spur interest into
      the identification of biomarkers able to define biologically homogeneous
      subgroups, predict autism risk prior to the onset of behavioural abnormalities,
      aid early diagnoses, predict the developmental trajectory of ASD children,
      predict response to treatment and identify children at risk for severe adverse
      reactions to psychoactive drugs. OBJECTIVES: The present paper reviews (a)
      similarities and differences between the concepts of 'biomarker' and
      'endophenotype', (b) established biomarkers and endophenotypes in autism research
      (biochemical, morphological, hormonal, immunological, neurophysiological and
      neuroanatomical, neuropsychological, behavioural), (c) -omics approaches towards
      the discovery of novel biomarker panels for ASD, (d) bioresource infrastructures
      and (e) data management for biomarker research in autism. RESULTS: Known
      biomarkers, such as abnormal blood levels of serotonin, oxytocin, melatonin,
      immune cytokines and lymphocyte subtypes, multiple neuropsychological,
      electrophysiological and brain imaging parameters, will eventually merge with
      novel biomarkers identified using unbiased genomic, epigenomic, transcriptomic,
      proteomic and metabolomic methods, to generate multimarker panels. Bioresource
      infrastructures, data management and data analysis using artificial intelligence
      networks will be instrumental in supporting efforts to identify these biomarker
      panels. CONCLUSIONS: Biomarker research has great heuristic potential in
      targeting autism diagnosis and treatment.

PMID- 24096535
TI  - Vendor differences in alcohol consumption and the contribution of dopamine
      receptors to Pavlovian-conditioned alcohol-seeking in Long-Evans rats.
AB  - RATIONALE: Drug-associated environmental stimuli elicit craving in humans and
      drug-seeking in animals. OBJECTIVES: We tested the hypothesis that Pavlovian
      conditioned alcohol-seeking is mediated by dopamine, using rats from two vendors.
      METHODS: Male, Long-Evans rats (220-240 g) from Charles River (St-Constant, QC,
      Canada) and Harlan Laboratories (Indianapolis, IN, USA) received 21 sessions of
      intermittent, 24-h access to ethanol (15 %, v/v) and water in the home-cage.
      Subsequently, rats were trained to discriminate between one conditioned stimulus
      (CS+) that was paired with ethanol (0.2 ml per CS+) and a second stimulus (CS-)
      that was not. Entries into a fluid port where ethanol was delivered were
      recorded. Next, rats were exposed to a different context where cues and ethanol
      were withheld. At test, responding to the CS+ and CS- without ethanol was
      assessed in the second, non-alcohol context. Injections (1 ml/kg; s.c.) of the
      dopamine D1-receptor antagonist SCH 23390 (0, 3.33, and 10 MUg/kg) or dopamine D2
      receptor antagonist eticlopride (0, 5, and 10 MUg/kg) were administered before
      test. RESULTS: Home-cage alcohol consumption was higher in Harlan rats than
      Charles River rats. At test, saline-treated rats responded more to the alcohol
      predictive CS+ than the CS-. While SCH 23390 attenuated CS+ responding in rats
      from both vendors, eticlopride reduced CS+ responding in Harlan rats only.
      Subsequently, SCH 23390 but not eticlopride attenuated CS+ responding when the
      CS+ was again paired with ethanol. CONCLUSIONS: These results indicate important
      differences in alcohol consumption in Long-Evans rats from different suppliers,
      and highlight a novel role for dopamine in Pavlovian-conditioned alcohol-seeking.

PMID- 24096536
TI  - Crocins, the active constituents of Crocus Sativus L., counteracted ketamine
      induced behavioural deficits in rats.
AB  - RATIONALE: Experimental evidence indicates that the non-competitive N-methyl-D
      aspartate (NMDA) receptor antagonist ketamine impairs cognition and can mimic
      certain aspects of positive and negative symptoms of schizophrenia in rodents.
      Crocins are among the active components of the plant Crocus sativus L. and were
      found to be effective in different models of psychiatric disorders including
      anxiety and depression. OBJECTIVES: The present study was designed to investigate
      the ability of crocins to counteract schizophrenia-like behavioural deficits
      produced by ketamine in rats. METHODS: Crocin's ability to counteract
      hypermotility, stereotypies and ataxia induced by ketamine was evaluated in a
      motor activity cage. The ability of crocins to reverse ketamine-induced memory
      deficits was assessed using the novel object recognition task (NORT). The social
      interaction test was used in order to examine the effects of crocins on ketamine
      induced social withdrawal. RESULTS: Crocins (50 but not 30 mg/kg, i.p.)
      attenuated ketamine (25 mg/kg, i.p.)-induced hypermotility, stereotypies and
      ataxia. In a subsequent study, post-training administration of crocins (15 and 30
      mg/kg, i.p.) reversed ketamine (3 mg/kg, i.p.)-induced performance deficits in
      the NORT. Finally, crocins (50 but not 30 mg/kg, i.p.) counteracted the ketamine
      (8 mg/kg, i.p.)-induced social isolation in the social interaction test.
      CONCLUSIONS: Our findings show that crocins attenuated schizophrenia-like
      behavioural deficits induced by the non-competitive NMDA receptor antagonist
      ketamine in rats.

PMID- 24096537
TI  - Specifying the non-specific factors underlying opioid analgesia: expectancy,
      attention, and affect.
AB  - RATIONALE: Psychological processes such as expectancy, attention, and affect
      directly influence clinical outcomes. These factors are grouped together as
      "nonspecific" factors, or placebo effects, in the medical literature, and their
      individual contributions are rarely considered. The pain-reducing effects of
      analgesic treatments may reflect changes in these psychological factors, rather
      than pure drug effects on pain. Furthermore, drug effects may not be isolated by
      drug vs. placebo comparisons if drugs interact with relevant psychological
      processes. OBJECTIVES: We sought to determine whether the analgesic effects of
      opioid and placebo treatment are mediated by changes in attention, expectancy, or
      affect. METHODS: We crossed intravenous administration of a potent opioid
      analgesic, remifentanil, with information about drug delivery (treatment
      expectancy or placebo) using a balanced placebo design. We measured drug and
      treatment expectancy effects on pain, attention, and responses to emotional
      images. We also examined interactions with cue-based expectations about noxious
      stimulation or stimulus expectancy. RESULTS: Pain was additively influenced by
      treatment expectancy, stimulus expectancy, and drug concentration. Attention
      performance showed a small but significant interaction between drug and treatment
      expectancy. Finally, remifentanil enhanced responses to both positive and
      negative emotional images. CONCLUSIONS: The pain-relieving effects of opioid
      drugs are unlikely to be mediated by changes in threat or affective processing.
      Standard open-label opioid administration influences multiple clinically relevant
      cognitive and emotional processes. Psychological factors can combine with drug
      effects to influence multiple outcomes in distinct ways. The influence of
      specific psychological factors should be considered when developing and testing
      pharmacological treatments.

PMID- 24096538
TI  - Effects of repeated exposure to morphine in adolescent and adult male C57BL/6J
      mice: age-dependent differences in locomotor stimulation, sensitization, and body
      weight loss.
AB  - RATIONALE: Given evidence for age-related differences in the effects of drugs of
      abuse, surprisingly few preclinical studies have explored effects of opioids in
      adolescents (versus adults). OBJECTIVES: This study compared the motor
      stimulating and ataxic effects of repeatedly administered morphine in adolescent,
      late adolescent, and adult mice. METHODS: Mice were treated with saline or
      morphine (10-100 mg/kg, i.p.) once per day for 4 days, and morphine (3.2-56
      mg/kg)-induced locomotion was assessed 3 days or 5 weeks later. Different mice
      were treated repeatedly with morphine and ataxia was measured. RESULTS: Acute
      administration of morphine increased locomotion more in adolescents than in
      adults. Repeated morphine enhanced morphine-induced locomotion, assessed 3 days
      later, to a similar extent in each age group (minimum effective dose 17.8 mg/kg).
      This sensitization was still evident 5 weeks later when the adolescents had
      become adult, but was smaller and occurred at a higher dose (56 mg/kg). In
      animals treated repeatedly with morphine as adults, sensitization was no longer
      apparent 5 weeks later. Intermittent morphine was at least 10-fold less potent to
      produce body weight loss in adolescents than in adults. Repeated morphine did not
      alter morphine-induced ataxia at any age. CONCLUSIONS: Compared with adults,
      adolescents were more sensitive to the acute locomotor stimulating effects of
      morphine and to its long-lasting locomotor sensitizing effects, consistent with
      overactivity of dopamine systems during adolescence. In contrast, adolescents
      were less sensitive than adults to body weight loss induced by intermittent
      morphine, an effect indicative of morphine withdrawal in adult rodents.

PMID- 24096539
TI  - Nanoplatforms for highly sensitive fluorescence detection of cancer-related
      proteases.
AB  - Numerous proteases are known to be necessary for cancer development and
      progression including matrix metalloproteinases (MMPs), tissue serine proteases,
      and cathepsins. The goal of this research is to develop an Fe/Fe3O4 nanoparticle
      based system for clinical diagnostics, which has the potential to measure the
      activity of cancer-associated proteases in biospecimens. Nanoparticle-based
      "light switches" for measuring protease activity consist of fluorescent cyanine
      dyes and porphyrins that are attached to Fe/Fe3O4 nanoparticles via consensus
      sequences. These consensus sequences can be cleaved in the presence of the
      correct protease, thus releasing a fluorescent dye from the Fe/Fe3O4
      nanoparticle, resulting in highly sensitive (down to 1 * 10(-16) mol l(-1) for 12
      proteases), selective, and fast nanoplatforms (required time: 60 min). 

PMID- 24096540
TI  - RhoA and RhoC differentially modulate estrogen receptor alpha recruitment,
      transcriptional activities, and expression in breast cancer cells (MCF-7).
AB  - PURPOSE: RhoA and RhoC are closely related, small GTPases that are clearly
      involved in breast cancer tumorigenesis. Nonetheless, their specific roles in the
      control of estrogen receptor alpha (ERalpha) activities have not been elucidated.
      METHODS: We used siRNA sequences to specifically down-regulate RhoA and RhoC
      expression in ERalpha-positive breast adenocarcinoma MCF-7 cells. We then
      analyzed the consequences of down-regulation on ERalpha expression, ERalpha
      recruitment to the promoters of four target genes, and the mRNA levels of those
      genes. RESULTS: We demonstrated that RhoA and RhoC clearly and similarly
      modulated ERalpha recruitment to the vitellogenin estrogen responsive element
      (ERE) present in a luciferase reporter gene and to the promoters of progesterone
      receptor (PR), cathepsin D, and pS2 genes. Besides, RhoA up-regulated the ERE
      luciferase reporter gene activity and PR mRNA expression and tended to down
      regulate cathepsin D and pS2 mRNA expression. Conversely, RhoC inhibition had no
      significant effect at the mRNA level. Furthermore, RhoA inhibition, and to a
      lesser extent RhoC inhibition, increased ERalpha expression. No alteration in
      ERalpha mRNA levels was observed, suggesting potential post-translational
      control. CONCLUSIONS: Taken together, our results strongly suggest that RhoA and
      RhoC play different, but clear, roles in ERalpha signaling. These GTPases are
      definitely involved, along with RhoB, in ERalpha recruitment and, to some extent,
      ERalpha cofactor balance. We hypothesize a differential role of RhoA in breast
      cancer tumors that depend on hormone status.

PMID- 24096541
TI  - Imaging energy status in live cells with a fluorescent biosensor of the
      intracellular ATP-to-ADP ratio.
AB  - The ATP:ADP ratio is a critical parameter of cellular energy status that
      regulates many metabolic activities. Here we report an optimized genetically
      encoded fluorescent biosensor, PercevalHR, that senses the ATP:ADP ratio.
      PercevalHR is tuned to the range of intracellular ATP:ADP expected in mammalian
      cells, and it can be used with one- or two-photon microscopy in live samples. We
      use PercevalHR to visualize activity-dependent changes in ATP:ADP when neurons
      are exposed to multiple stimuli, demonstrating that it is a sensitive reporter of
      physiological changes in energy consumption and production. We also use
      PercevalHR to visualize intracellular ATP:ADP while simultaneously recording
      currents from ATP-sensitive potassium (KATP) channels in single cells, showing
      that PercevalHR enables the study of coordinated variation in ATP:ADP and KATP
      channel open probability in intact cells. With its ability to monitor changes in
      cellular energetics within seconds, PercevalHR should be a versatile tool for
      metabolic research.

PMID- 24096542
TI  - Tissue-engineered skin substitutes: an overview.
AB  - Extensive skin loss and chronic wounds are still a significant challenge to
      clinicians: even if injured epidermis is normally able to self-renew, deep
      injuries can cause negative regulation of the wound healing cascade, leading to
      chronic wound formation. Skin-autografting surgical procedures are often limited
      by the poor availability of healthy tissue, whereas the use of non-self-tissues
      for allografts presents some severe risks. Tissue-engineered skin substitutes
      have recently become viable as a suitable alternative to auto- and allografts.
      However, biologists, biochemists, and technical engineers are still struggling to
      produce complex skin substitutes that can readily be transplanted in large
      quantities. The ambitious goal is now to construct a dermoepidermal substitute
      that rapidly vascularizes and optimally supports a stratifying epidermal graft on
      a biodegradable matrix. This review analyzes these aspects in light of the
      available literature and the authors' experience. 

PMID- 24096543
TI  - Incidence of skeletal fractures after traumatic spinal cord injury: a 10-year
      follow-up study.
AB  - OBJECTIVE: To analyse the incidence and factors related to the development and
      clinical evolution of fractures in patients with traumatic spinal cord injury.
      DESIGN: A retrospective 10-year follow-up study. SETTING: Neurorehabilitation
      centre. SUBJECTS: Sixty-three patients (50M/13F) with a mean age of 36 +/- 20
      years with recent traumatic spinal cord injury attended over a one-year period
      (January to December 2000). MAIN MEASURES: Medical reports were reviewed,
      evaluating risk factors for osteoporosis, fracture incidence during the 10 years
      following spinal cord injury, severity (ASIA score) and level of spinal cord
      injury (paraplegia/tetraplegia), type of lesion (spastic/flaccid), weight-bearing
      standing activity, and the cause, location and evolution of the fracture.
      RESULTS: Of the 129 patients attending during the study period, 75 had traumatic
      spinal cord injury (7 died and 5 had no follow-up). Finally, 63 patients were
      included. Fifty-four per cent had complete motor injury (ASIA A). Twenty-five per
      cent of these patients developed fractures, with 2.9 fractures per 100 patient
      years. The femur was the most frequent location of the fractures. Fractures were
      observed 6.4 +/- 2.4 years after spinal cord injury (range 2-10 years), all in
      males. Most fractures (70%) were related to low-impact injuries. Fifty per cent
      presented with associated clinical complications and only 20% of the patients had
      received anti-osteoporotic treatment. Spinal cord injury severity was the only
      risk factor for the development of fractures (complete spinal cord injury (ASIA
      A)) (RR 4.043; 95% confidence interval (CI) 1.081-23.846, P = 0.037). CONCLUSION:
      The incidence of fractures after spinal cord injury is high, with severity and
      time since spinal cord injury being the main determinants for their development.
      Fractures were frequently associated with clinical complications. However, the
      use of anti-osteoporotic treatment was uncommon.

PMID- 24096544
TI  - Survivin rs9904341 (G>C) polymorphism contributes to cancer risk: an updated meta
      analysis of 26 studies.
AB  - Survivin, a member of the inhibitor of apoptosis protein family, encoded by
      BIRC5, is involved in the regulation of apoptosis and in cell cycle control.
      Emerging evidences indicate that polymorphism in BIRC5 promoter (rs9904341) is
      associated with cancer risk, but the results of individually published studies
      are inconclusive. Thus, an updated meta-analysis was performed. PubMed was
      searched for all eligible studies. Pooled odds ratios (ORs) and 95 % confidence
      intervals (CIs) were calculated to assess the association strength. Stratified
      analysis was performed by cancer type, source of control, genotyping method, and
      ethnicity. A number of 26 studies, including 6,041 cases and 7,567 controls were
      analyzed in this meta-analysis. Overall, significantly increased cancer risk was
      associated with survivin rs9904341 polymorphism when all studies were pooled (CC
      vs. GG: OR = 1.36, 95 % CI = 1.09-1.69; P heterogeneity < 0.001; CC vs GC/GG: OR
      = 1.32, 95 % CI = 1.11-1.57; P heterogeneity < 0.001). Stratified analysis by
      cancer type revealed that the survivin rs9904341 polymorphism may increase the
      risk of colorectal cancer, renal cell cancer, gastric cancer, and bladder cancer.
      Further subgroup analysis by ethnicity indicated that there was a statistically
      increased cancer risk in Asians but not Caucasians. In this updated meta-analysis
      of 26 studies, we conclude that the survivin rs9904341 polymorphism might
      contribute to risk of various cancers, especially in Asian populations.

PMID- 24096545
TI  - QM-FISH analysis of the genes involved in the G1/S checkpoint signaling pathway
      in triple-negative breast cancer.
AB  - This study was conducted to analyze copy number alterations (CNAs) of the genes
      involved in the G1/S checkpoint signaling pathway of triple-negative breast
      cancer (TNBC) and to evaluate their clinical value in the prognosis of TNBC.
      Quantitative multi-gene fluorescence in situ hybridization was used to study CNAs
      of the genes involved in the G1/S checkpoint signaling pathway, including cyclin
      d1 (CCND1), c-Myc, p21, cell-cycle-checkpoint kinase 2 gene, p16, retinoblastoma
      (Rb1), murine double minute 2 (Mdm2) and p53, in 60 TNBC samples and 60 non-TNBC
      samples. In comparison with the non-TNBC samples, CNAs of the genes involved in
      the G1/S checkpoint signaling pathway were more frequently observed in the TNBC
      samples (p = 0.000). Out of a total of eight genes, six (CCND1, c-Myc, p16, Rb1,
      Mdm2, and p53) exhibited significantly different CNAs between the TNBC group and
      the non-TNBC group. Univariate survival analysis revealed that the gene
      amplification of c-Myc (p = 0.008), Mdm2 (p = 0.020) and the gene deletion of p21
      (p = 0.004), p16 (p = 0.015), and Rb1 (p = 0.028) were the independent predictive
      factor of 5-year OS for patients with TNBC. Cox multivariate analysis revealed
      that the gene amplification of c-Myc (p = 0.026) and the gene deletion of p21 (p
      = 0.019) and p16 (p = 0.034) were independent prognostic factors affecting the 5
      year OS for TNBC. CNAs of the genes involved in the G1/S checkpoint signaling
      pathway presented a higher rate of incidence in TNBC than in non-TNBC, which
      could indicate one of the molecular mechanisms for the specific biological
      characteristics of TNBC. The genes c-Myc, p21, and p16 were correlated with the
      prognosis of TNBC and therefore may have potential clinical application values in
      the prognostic prediction of TNBC. 

PMID- 24096547
TI  - New trichoscopy findings in trichotillomania: flame hairs, V-sign, hook hairs,
      hair powder, tulip hairs.
AB  - Differential diagnosis of trichotillomania is often difficult in clinical
      practice. Trichoscopy (hair and scalp dermoscopy) effectively supports
      differential diagnosis of various hair and scalp diseases. The aim of this study
      was to assess the usefulness of trichoscopy in diagnosing trichotillomania. The
      study included 370 patients (44 with trichotillomania, 314 with alopecia areata
      and 12 with tinea capitis). Statistical analysis revealed that the main and most
      characteristic trichoscopic findings of trichotillomania are: irregularly broken
      hairs (44/44; 100% of patients), v-sign (24/44; 57%), flame hairs (11/44; 25%),
      hair powder (7/44; 16%) and coiled hairs (17/44; 39%). Flame hairs, v-sign, tulip
      hairs, and hair powder were newly identified in this study. In conclusion, we
      describe here specific trichoscopy features, which may be applied in quick, non
      invasive, in-office differential diagnosis of trichotillomania.

PMID- 24096546
TI  - Clinical pathological characteristics and prognostic analysis of diabetic women
      with luminal subtype breast cancer.
AB  - This study selected luminal-type breast cancer patients as the study subjects.
      The patients were divided into groups according to the presence of diabetes and
      the types of medication used, and the patients' clinicopathological
      characteristics and prognostic indicators were explored. A total of 5,785
      patients with luminal-type breast cancer admitted to Tianjin Medical University
      Cancer Institute and Hospital between January 2002 and December 2006 were
      selected as the study subjects. The subjects included 680 breast cancer patients
      with diabetes and 5,105 breast cancer patients without diabetes. The patients
      were divided into Luminal A, Luminal B (high ki67), and Luminal B (her-2/neu+)
      subtypes. Each subtype was further divided into a metformin group, a non
      metformin group, and a nondiabetic group. The research indicators included breast
      cancer mortality, age, body mass index (BMI), amenorrhea, the presence of
      cardiovascular and cerebrovascular disease, pathological stage, pathological
      type, lymph node involvement, vessel carcinoma embolus, and the chemotherapy and
      endocrine regimen. A Kaplan-Meier analysis was conducted to analyze the
      differences in breast cancer mortality rates among the groups. The Cox
      proportional hazard model was adopted to detect independent factors related to
      prognosis. Kaplan-Meier univariate analysis showed that for the Luminal A,
      Luminal B (high ki67), and Luminal B (her-2/neu+) subtypes, the cancer-specific
      mortality rates differed significantly among the metformin, non-metformin, and
      nondiabetic groups. The 5-year survival rates were 94%, 82%, and 91% (P = 0.002);
      93.5%, 81%, and 89% (P < 0.001); and 84%, 77%, and 83% (P = 0.035) for the
      subtypes within each group, respectively. Cox regression multivariate analysis
      showed that compared with the metformin group, all three subtypes of the, the non
      metformin group showed poorer prognosis (hazard ratio [HR], 3.579; 95% confidence
      interval [CI], 1.506-8.506 [P = 0.004]; HR, 3.232; 95% CI, 1.839-5.678 [P <
      0.001]; HR, 2.034; 95% CI,1.019-4.059 [P = 0.044] for Luminal A, Luminal B (high
      ki67), and Luminal B (her-2/neu+, respectively). Compared with the metformin
      group, the diabetic group showed poorer prognosis only for the Luminal B (high
      ki67) subtype (HR, 1.762; 95% CI, 1.033-3.005 [P = 0.038]). In addition, for the
      Luminal A, Luminal B (high ki67), and Luminal B (her-2/neu+) subgroups, there was
      a higher proportion of elderly patients (P < 0.001) and postmenopausal patients
      (P < 0.001) in the metformin and non-metformin groups than in the nondiabetic
      group. Moreover, the probability of having cardiovascular and cerebrovascular
      disease was also higher (P < 0.001) in the metformin and non-metformin groups.
      For the Luminal B (high ki67) and Luminal B (her-2/neu +) subgroups, there was a
      higher proportion of obese patients in the metformin and non-metformin groups (P
      < 0.001). In terms of clinical characteristics, for the Luminal B (high ki67)
      subtype, the proportion of patients with invasive ductal carcinoma was lower in
      the non-metformin group than in the other two groups (P = 0.001). In both the
      metformin and non-metformin groups, the proportion of T3/4 patients was higher (P
      < 0.001), the proportion of patients with lymph node metastasis was higher (P =
      0.001), and the proportion of patients with vessel carcinoma embolus was higher
      (P = 0.001) compared with the nondiabetic group. In conclusion, compared with the
      metformin group, the non-metformin group had a poorer prognosis for all subtypes
      of luminal breast cancer. In the diabetic group, only patients with the Luminal B
      (high ki67) subtype exhibited a poorer prognosis. Therefore, different diabetes
      medication may have a different impact on the prognosis of different subtypes of
      luminal breast cancer.

PMID- 24096548
TI  - Honoring nurses who serve.

PMID- 24096549
TI  - What nurse practitioners should know about gene therapy.
AB  - The application of gene therapy to human patients has grown tremendously in
      recent years. Study findings have allowed scientists to develop newer genomic
      approaches to managing patients with chronic diseases. Nurse practitioners must
      be prepared to collaborate with the medical community to provide patients support
      and essential education about gene therapy treatment.

PMID- 24096550
TI  - Preventing stroke in patients with atrial fibrillation.
AB  - Adults with atrial fibrillation are at an increased risk for stroke. New oral
      antithrombotic agents are now available to help prevent stroke and other
      thromboembolic events. This article provides an update on factors to consider
      when determining various treatment options for these high-risk patients in hopes
      of improving outcomes.

PMID- 24096552
TI  - Copper supplementation at 8 mg neither affects circulating lipids nor liver
      function in apparently healthy Chilean men.
AB  - Copper (Cu) deficiency has been reported to influence lipid metabolism, but the
      effects in humans are controversial. To evaluate the effects of 8 mg Cu/day
      supplementation (as copper sulfate) for 6 months on the lipid profile and hepatic
      function of apparently healthy men. The design was randomized double-blind
      placebo-controlled clinical trial. SUBJECTS AND METHODS: 60 apparently healthy
      males aged 18-51 years were randomly assigned to Cu supplementation (n = 30) or
      placebo (n = 30). There was a nonsignificant reduction of 17 % in total
      cholesterol in both groups after supplementation. A 23 % nonsignificant reduction
      was observed in LDL cholesterol levels in the supplemented group. There was a
      nonsignificant increase of HDL cholesterol of 47 and 66 % in the control and
      supplemented groups, respectively. Triglyceride levels over 150 mg/dl were found
      in 17 subjects supplemented and 13 controls at baseline and decreased after
      supplementation to seven and eight subjects, respectively. There were no effects
      on serum Cu concentration or ceruloplasmin (protein) and hepatic transaminases.
      Supplementation of 8 mg Cu for 6 months had no effect on lipid profile of
      apparently healthy Chilean men with adequate Cu status.

PMID- 24096551
TI  - Preservation of bone structure and function by Lithothamnion sp. derived
      minerals.
AB  - Progressive bone mineral loss and increasing bone fragility are hallmarks of
      osteoporosis. A combination of minerals isolated from the red marine algae,
      Lithothamnion sp. was examined for ability to inhibit bone mineral loss in female
      mice maintained on either a standard rodent chow (control) diet or a high-fat
      western diet (HFWD) for 5, 12, and 18 months. At each time point, femora were
      subjected to MU-CT analysis and biomechanical testing. A subset of caudal
      vertebrae was also analyzed. Following this, individual elements were assessed in
      bones. Serum levels of the 5b isoform of tartrate-resistant acid phosphatase
      (TRAP) and procollagen type I propeptide (P1NP) were also measured. Trabecular
      bone loss occurred in both diets (evident as early as 5 months). Cortical bone
      increased through month 5 and then declined. Cortical bone loss was primarily in
      mice on the HFWD. Inclusion of the minerals in the diet reduced bone mineral loss
      in both diets and improved bone strength. Bone mineral density was also enhanced
      by these minerals. Of several cationic minerals known to be important to bone
      health, only strontium was significantly increased in bone tissue from animals
      fed the mineral diets, but the increase was large (5-10 fold). Serum levels of
      TRAP were consistently higher in mice receiving the minerals, but levels of P1NP
      were not. These data suggest that trace minerals derived from marine red algae
      may be used to prevent progressive bone mineral loss in conjunction with calcium.
      Mineral supplementation could find use as part of an osteoporosis-prevention
      strategy.

PMID- 24096553
TI  - Protein tyrosine phosphatase 1B inhibitory activities of ursane- and lupane-type
      triterpenes from Sorbus pohuashanensis.
AB  - Protein tyrosine phosphatase 1B (PTP1B) is a non-transmembrane protein tyrosine
      phosphatase, and has received much attention as a molecular target for the
      treatment of insulin resistance diseases because of its critical roles in
      negatively regulating insulin- and leptin-signaling cascades. Six ursane-type
      triterpenes, 3beta-acetoxy-urs-12-ene-28-oic acid (1), pomolic acid-3beta-acetate
      (2), pomolic acid (3), ursolaldehyde (4), euscaphic acid (5) and 3beta-acetoxy
      urs-11-en-28,13-olide (6), and a lupane-type triterpene, betulinic acid (7), from
      the fruits of Sorbus pohuashanensis, exhibited significant PTP1B inhibitory
      activity, with IC50 values ranging from 3.5 to 54.8 MUM. Kinetics analyses
      revealed that compounds 2, 3, and 7 are non-competitive PTP1B inhibitors, and
      compounds 1 and 6 are mixed-type PTP1B inhibitors.

PMID- 24096554
TI  - Preserved prognostic value of preinterventional troponin T levels despite
      successful TAVI in patients with severe aortic stenosis.
AB  - BACKGROUND: Elevated concentrations of troponin T have prognostic impact in
      patients with various cardiovascular diseases including those with severe aortic
      stenosis. Transcatheter aortic valve implantation (TAVI) has improved prognosis
      for patients without a surgical option. Whether this affects the prognostic value
      of preinterventional troponin T remains unclear. METHODS: We therefore conducted
      a prospective study in 198 consecutive patients with subsequent, successful
      transfemoral TAVI and analyzed cardiac troponin T (cTnT) levels with a new
      generation, high-sensitive troponin T assay before and after TAVI, as well as
      their prognostic value after 12 months. RESULTS: Patients with severe aortic
      stenosis (AS) showed significant elevation of preinterventional cTnT levels.
      Postinterventional cTnT levels significantly rose further about sevenfold after
      transfemoral TAVI and peaked at day three until they steadily declined
      thereafter. Baseline renal function (P = 0.011), the duration of intraprocedural
      rapid pacing (P = 0.0012), and baseline cTnT (P = 0.0001) values predicted the
      magnitude of postinterventional cTnT elevations. Interestingly, Kaplan-Meier
      curve analysis revealed, that although cTnT levels were not predictive for short
      term mortality, preinterventional as well as postinterventional peak cTnT showed
      prognostic value for 1-year mortality, regardless of successful TAVI.
      CONCLUSIONS: Pre- and postinterventional hscTnT levels signal adverse 1-year
      mortality in patients with severe AS independent of successful aortic valve
      replacement.

PMID- 24096555
TI  - Impact of real-time contact force and impedance measurement in pulmonary vein
      isolation procedures for treatment of atrial fibrillation.
AB  - BACKGROUND: Pulmonary vein isolation (PVI) is an established procedure to treat
      atrial fibrillation (AF). New techniques are necessary to improve procedural
      parameters like shortening of procedure duration. Real-time contact force (CF)
      catheters are new tools aiming to improve PVI by optimizing electrode-tissue
      contact and generating more effective lesions. Objective of this study was to
      investigate the influence on procedural parameters and clinical outcome by using
      a CF catheter for PVI. METHODS: PVI was performed on 67 consecutive patients
      using a CF catheter (n = 32) or a standard ablation catheter (SAC, n = 35). Study
      endpoints included number of energy applications, impedance drop, fluoroscopy
      time, and left atrial (LA) procedure time and freedom from AF after 6 and 12
      months. RESULTS: Procedural endpoint was reached in all patients with a similar
      clinical outcome (freedom from AF) in both groups 6 months (62.9 vs. 62.5%) and
      12 months post PVI (59.4 vs. 62.9% in CF vs. SAC group, respectively). However,
      CF-guided ablation resulted in a greater fall of impedance (6.58 +/- 0.33 vs.
      9.09 +/- 0.53 Omega, *** p < 0.001), lower number of energy applications (44.20
      +/- 3.67 vs. 34.06 +/- 3.11, * p < 0.05), reduction of LA procedure time (95.52
      +/- 7.35 vs. 78.08 +/- 7.23* min) and a significant reduction of fluoroscopy time
      (51.4 +/- 3.3 vs. 33.0 +/- 2.7*** min). In addition, a detailed analysis showed a
      significant correlation between quantitative impedance drop and amount of CF
      applied, suggesting more efficient lesion creation by CF-guided ablation.
      CONCLUSION: Use of CF catheters in PVI has a beneficial effect on procedural
      parameters, probably by improving efficacy of transmural lesion formation.

PMID- 24096557
TI  - The learned physician as a charismatic healer: Urso of Salerno (flourished end of
      twelfth century) on incantations in medicine, magic, and religion.
AB  - Urso, the last of the great Salernitan physicians, was both an ardent defender of
      a theoretical, scientific medicine and the first in the medieval West to propose,
      in his aphorisms, a rational and naturalistic explanation of the healing power of
      incantations. The article explores this paradox and provides an in-depth analysis
      of Urso's highly original and hitherto ignored argument, as well as its
      intellectual and social background. According to Urso, the efficacy of
      incantations relies not on the power of words, but on the charismatic physician's
      "aura"-spirits emanating from his body-and the patient's confidence in and
      conformity with the physician. Urso compares medical incantations to teaching,
      fascination, demonic magic, sacraments, and prayer. It is argued that Urso's
      incursions into theology are both a tactic to defend his bold naturalism against
      accusations of unorthodoxy and a reflection of his ambition to create a
      comprehensive "science of everything." Urso's text and an English translation are
      provided in an appendix.

PMID- 24096556
TI  - Estrogen oversees the maintenance of the female genetic program in terminally
      differentiated gonochorists.
AB  - The sexual plasticity of the gonads is not retained after the completion of sex
      differentiation in vertebrates, except in some hermaphroditic species. Here, we
      report that the depletion of estradiol-17beta (E2) by aromatase inhibitors (AI)
      for up to six months resulted in a functional female-to-male sex reversal in
      sexually-mature adults of two gonochoristic fish species, Nile tilapia and
      medaka. The sex-reversed fish showed a typical male pattern of E2 and androgen
      levels, secondary sexual characteristics, and male-like sex behavior, producing
      fertile sperm. Conversely, co-treatment of E2 inhibited AI-induced sex reversal.
      In situ hybridization of medaka gonads during AI-induced sex reversal indicated
      that cysts on the dorsal side of the adult ovaries are the origin of germ cells
      and Sertoli cells in the newly formed testicular tissue. Gonochoristic fish
      maintain their sexual plasticity until adulthood and E2 plays a critical role in
      maintaining the female phenotype. 

PMID- 24096558
TI  - Curtis's cephaloscope: deafness and the making of surgical authority in London,
      1816-1845.
AB  - Aural surgery is a branch of nineteenth-century medicine and surgery providing
      specialized treatment for ear diseases. During the 1830s, faced with a "popular
      prejudice" against the curability of deafness as well as intraprofessional
      rivalries and continuous accusations of quackery, aurists found their surgical
      authority questioned and their field's value threatened. In an attempt to bolster
      aural surgery's reputation, in 1841, the aurist John Harrison Curtis (1778-1856)
      introduced his new diagnostic instrument, the cephaloscope, which could not only
      improve diagnosis but also provide approaches for regulating aural knowledge,
      thus strengthening aural surgery's authority. This article examines the motives
      underlying Curtis's introduction of the cephaloscope and the meanings it held for
      the occupational group at large.

PMID- 24096559
TI  - "Children with half-starved bodies" and the assessment of malnutrition in the
      United States, 1890-1950.
AB  - Malnutrition was one of the most significant children's health issues of the
      early twentieth century, but it also engendered considerable controversy. Just
      how many children were truly malnourished, and how could they be reliably
      identified? Despite the failures of numerous diagnostic methods-even the
      definition of malnutrition defied consensus-health authorities remained convinced
      that malnutrition was a serious and widespread problem. Indeed, the imprecision
      that surrounded the condition allowed it to be used metaphorically to advance a
      broad range of professional, social, and public health agendas. By the 1940s, due
      in part to the lack of reliable diagnostic methods, public health nutrition
      policy shifted abruptly from one of assessment, based on mass surveillance and
      individualized care, to one of management, based on a universal program of
      nutrition education, fortification of foods, and food security that treated all
      children as in need of nutritional assistance.

PMID- 24096560
TI  - A mother's responsibility: women, medicine, and the rise of contemporary vaccine
      skepticism in the United States.
AB  - Federal efforts to expand childhood immunization coverage in the United States in
      the 1970s relied heavily on the cooperation of mothers and were concurrent with a
      major social movement of the past century: the women's movement. This article
      examines popular and scientific immunization rhetoric of the 1970s and 1980s
      through a feminist lens, to demonstrate how changing ideas about the social and
      economic roles of women in this period shaped, on the one hand, official
      vaccination recommendations and, on the other, women's acceptance of vaccines
      recommended for their children. Notably, the feminist and women's health
      movements changed the way women related to and perceived doctors, medical advice,
      and scientific expertise, with important implications for how some women
      perceived vaccines and their attendant risks. The influence of feminist ideas on
      the vaccine doubts that took shape in this period reveal the complexity of the
      ideologies informing the rise of contemporary vaccine skepticism.

PMID- 24096561
TI  - American Association for the History of Medicine: report of the eighty-sixth
      annual meeting.

PMID- 24096564
TI  - Retraction. Human T-cell lymphotropic virus type 1 infection of CD34+
      hematopoietic progenitor cells induces cell cycle arrest by modulation of
      p21(cip1/waf1) and survivin.

PMID- 24096565
TI  - Determination and pharmacokinetic study of the diacid metabolite of
      norcantharidin in beagle plasma by use of liquid chromatography-tandem mass
      spectrometry.
AB  - Because norcantharidin (NCTD) is unstable and subject to ring opening and
      hydrolysis, the diacid metabolite of norcantharidin (DM-NCTD) is the stable form
      of NCTD found in normal saline solution. Conversion of NCTD to DM-NCTD is almost
      100%, making it possible to determine and investigate the pharmacokinetics of DM
      NCTD converted from NCTD. In this paper, a sensitive, simple and selective liquid
      chromatographic-tandem mass spectrometric method was developed and validated for
      determination of DM-NCTD in beagle plasma. DM-NCTD was detected in multiple
      reaction monitoring (MRM) mode by using the dehydrated ion 169.3 as precursor ion
      and its product ion 123.1 as the detected ion. Ribavirin was used as internal
      standard and detected in MRM mode by use of precursor ions, resulting in a
      product ion transition of m/z 267.1 -> 135.1. This method was successfully used
      for a pharmacokinetic study of DM-NCTD in beagles after intravenous
      administration of DM-NCTD in normal saline solution at doses of 0.39, 0.78, and
      1.6 mg kg(-1). DM-NCTD had dose-dependent kinetics across the dosage range
      investigated, with enhanced T(1/2alpha) and AUC(0-12) and apparently decreasing
      V(d) and CL with increasing dosage. After single-dose administration, T(1/2alpha)
      ranged from 0.20 to 0.55 h, AUC(0-12) from 1.81 to 43.6 MUg mL(-1) h(-1), V(d)
      from 228 to 55.9 mL kg(-1), and CL from 220 to 36.5 mL kg(-1) h(-1) (P < 0.01).
      The results indicated nonlinear pharmacokinetic behavior of DM-NCTD in beagles,
      suggesting that the risk of DM-NCTD in normal saline solution intoxication may be
      non-proportionally increased at higher doses.

PMID- 24096566
TI  - Application of dried spot cards as a rapid sample treatment method for
      determining hydroxytyrosol metabolites in human urine samples. Comparison with
      microelution solid-phase extraction.
AB  - Two different rapid sample pretreatment strategies, dried spot cards, and
      microelution solid-phase extraction plates (MUSPE), with ultra-high performance
      liquid chromatography coupled to tandem mass spectrometry (UPLC-MS/MS) have been
      developed and validated for the determination of hydroxytyrosol and its
      metabolites in spiked human urine samples. Hydroxytyrosol, hydroxytyrosol-3'-O
      glucuronide, hydroxytyrosol-4'-O-glucuronide, hydroxytyrosol-3-O-sulphate, and
      homovanillic alcohol-4'-O-glucuronide were used as the target compounds. Using
      the FTA DMPK-A dried urine spot card under optimum conditions, with 5 MUL of
      preconcentrated urine volume and 100 MUL of methanol/water (50/50, v/v) as the
      elution solvent, the extraction recovery (%R) of the compounds studied was higher
      than 80%, and the matrix effect (%ME) was less than 8%. The stability of these
      cards and punching at the centre or side of the card were also studied, obtaining
      an excellent stability after 7 days of storage and complete homogeneity across
      the surface of the dried drop. The different MUSPE parameters that affect the
      efficiency were also studied, and under optimum conditions, the %R and the %ME
      were higher than 70% and lower than 17%, respectively. The linearity range in
      dried urine spot cards was 2.5-20 MUM for all the metabolites, with the exception
      of hydroxytyrosol-3-O-sulphate and hydroxytyrosol, which were 0.3-70 MUM and 2.5
      50 MUM respectively. With regards to MUSPE, the linearity range was 0.5-5 MUM for
      all the studied compounds, except for hydroxytyrosol-3-O-sulphate, which was 0.08
      5 MUM. The quantification limits (LOQs) were 0.3-2.5 MUM and 0.08-0.5 MUM in
      dried spot cards and in MUSPE, respectively. The two developed methods were then
      applied and compared for determining hydroxytyrosol and its metabolites in human
      24 h-urine samples after a sustained consumption (21 days) of a phenol-enriched
      virgin olive oil. The metabolites identified were hydroxytyrosol in its
      glucuronide and sulphate forms, homovanillic alcohol in its glucuronide and
      sulphate forms, homovanillic acid sulphate and hydroxytyrosol acetate sulphate.

PMID- 24096567
TI  - Simultaneous development of both competitive and noncompetitive immunoassays for
      2,2',4,4'-tetrabromodiphenyl ether using phage-displayed peptides.
AB  - Twenty-five phages that selectively bind to a monoclonal antibody (Mab) 1H2
      specific to 2,2',4,4'-tetrabromodiphenyl ether (BDE47) in the absence or presence
      of BDE47 have been selected from phage-display libraries containing cyclic 7-mer,
      linear 7-mer, and linear 12-mer randomized peptides. Competitive and
      noncompetitive enzyme-linked immunosorbent assays (ELISA) for BDE47 were
      developed by using a clone C7-1 specific to the BDE47-free Mab 1H2 and a clone
      XC7-8 specific to the BDE47-bound Mab 1H2, respectively. The half-maximum signal
      inhibition concentration (IC50) of the competitive phage ELISA and the half
      maximum signal enhancement concentration (EC50) of the noncompetitive phage ELISA
      for BDE47 were 6.8 ng mL(-1) and 4.2 ng mL(-1), respectively. The noncompetitive
      phage ELISA showed higher cross-reactivity with BDE28, BDE99, and BDE100 than the
      competitive one, ranging between 1.3 and 6.5 % versus 0.3 and 0.8 %. Recoveries
      of the competitive and the noncompetitive phage ELISAs for BDE47 in sewage sludge
      and fillet samples were 96-124 % and 97-120 %, respectively. The results of the
      two types of phage ELISAs for BDE47 in the real-world samples agreed well with a
      gas chromatography/electron capture detector-ion trap mass spectrometer method.

PMID- 24096569
TI  - Molecular disassembly of starch granules during gelatinization and its effect on
      starch digestibility: a review.
AB  - Starch is the most important glycemic carbohydrate in foods. The relationship
      between the rate and extent of starch digestion to produce glucose for absorption
      into the bloodstream and risk factors for diet-related diseases is of
      considerable nutritional interest. Native starch is attacked slowly by enzymes,
      but after hydrothermal processing its susceptibility to enzymatic breakdown is
      greatly increased. Most starch consumed by humans has undergone some form of
      processing or cooking, which causes native starch granules to gelatinize,
      followed by retrogradation on cooling. The extent of gelatinization and
      retrogradation are major determinants of the susceptibility of starch to
      enzymatic digestion and its functional properties for food processing. The type
      and extent of changes that occur in starch as a result of gelatinization, pasting
      and retrogradation are determined by the type of the starch, processing and
      storage conditions. A mechanistic understanding of the molecular disassembly of
      starch granules during gelatinization is critical to explaining the effects of
      processing or cooking on starch digestibility. This review focuses on the
      molecular disassembly of starch granules during starch gelatinization over a wide
      range of water levels, and its consequential effect on in vitro starch
      digestibility and in vivo glycemic index. 

PMID- 24096568
TI  - The molecular diversity of Luminal A breast tumors.
AB  - Breast cancer is a collection of diseases with distinct molecular traits,
      prognosis, and therapeutic options. Luminal A breast cancer is the most
      heterogeneous, both molecularly and clinically. Using genomic data from over
      1,000 Luminal A tumors from multiple studies, we analyzed the copy number and
      mutational landscape of this tumor subtype. This integrated analysis revealed
      four major subtypes defined by distinct copy-number and mutation profiles. We
      identified an atypical Luminal A subtype characterized by high genomic
      instability, TP53 mutations, and increased Aurora kinase signaling; these genomic
      alterations lead to a worse clinical prognosis. Aberrations of chromosomes 1, 8,
      and 16, together with PIK3CA, GATA3, AKT1, and MAP3K1 mutations drive the other
      subtypes. Finally, an unbiased pathway analysis revealed multiple rare, but
      mutually exclusive, alterations linked to loss of activity of co-repressor
      complexes N-Cor and SMRT. These rare alterations were the most prevalent in
      Luminal A tumors and may predict resistance to endocrine therapy. Our work
      provides for a further molecular stratification of Luminal A breast tumors, with
      potential direct clinical implications. 

PMID- 24096571
TI  - High-molecular-weight kininogen and the intrinsic coagulation pathway in patients
      with de novo acute myocardial infarction.
AB  - After an acute ischaemic event serum proteins may change reflecting the ischaemic
      damage. Proteomic studies could provide new insights into potential biomarkers in
      the evolution of ischaemic syndromes. In this study we have investigated the
      coordinated changes in coagulation-related proteins in the evolution after an
      acute myocardial infarction (AMI). Serum proteome (2D-electrophoresis and MALDI
      TOF/TOF) of AMI-patients within the first 6 hours after event onset (admission
      time) and 3 days after were compared to controls. Systems biology and
      bioinformatic analysis were performed to identify the differentially expressed
      canonical pathways. In silico analysis of differential proteins revealed changes
      in the intrinsic coagulation pathway in the early phase post-AMI. The two
      identified high-molecular weight kininogen (HMWK) clusters were inversely
      correlated in AMI patients at admission, being the intensity of the low-molecular
      weight form inversely related to myocardial necrosis (p<0.05). Factor XI (FXI)
      levels were decreased in AMI patients at admission and normalised 3 days after
      (p<0.05). There was an early increase in fibrinogen gamma and D-dimer at
      admission, followed by a decrease in fibrinogen turnover 3 days after (p<0.05).
      The influence of elapsed time of ischaemia on fibrinogen distribution changes was
      validated in coronary thrombi retrieved by thromboaspiration. In conclusion, our
      results demonstrate an active exchange between HMWK forms and a decrease in FXI
      indicative of intrinsic pathway activation, together with an increase in
      fibrinogen gamma turnover and D-dimer formation in the early phase post-AMI.
      Moreover, coronary thrombi showed a dynamic evolution in fibrinogen composition
      depending on the duration of ischaemia influencing serum fibrinogen-related
      products content. 

PMID- 24096570
TI  - Alterations of dystrophin-associated glycoproteins in the heart lacking
      dystrophin or dystrophin and utrophin.
AB  - Heart disease is a leading cause of death in patients with Duchenne muscular
      dystrophy (DMD). Patients with DMD lack the protein dystrophin, which is widely
      expressed in striated muscle. In skeletal muscle, the loss of dystrophin results
      in dramatically decreased expression of the dystrophin associated glycoprotein
      complex (DGC). Interestingly, in the heart the DGC is normally expressed without
      dystrophin; this has been attributed to presence of the dystrophin homologue
      utrophin. We demonstrate here that neither utrophin nor dystrophin are required
      for the expression of the cardiac DGC. However, alpha-dystroglycan (alpha-DG), a
      major component of the DGC, is differentially glycosylated in dystrophin-(mdx)
      and dystrophin-/utrophin-(dko) deficient mouse hearts. In both models the altered
      alpha-DG retains laminin binding activity, but has an altered localization at the
      sarcolemma. In hearts lacking both dystrophin and utrophin, the alterations in
      alpha-DG glycosylation are even more dramatic with changes in gel migration
      equivalent to 24 +/- 3 kDa. These data show that the absence of dystrophin and
      utrophin alters the processing of alpha-DG; however it is not clear if these
      alterations are a consequence of the loss of a direct interaction with
      dystrophin/utrophin or results from an indirect response to the presence of
      severe pathology. Recently there have been great advances in our understanding of
      the glycosylation of alpha-DG regarding its role as a laminin receptor. Here we
      present data that alterations in glycosylation occur in the hearts of animal
      models of DMD, but these changes do not affect laminin binding. The physiological
      consequences of these alterations remain unknown, but may have significant
      implications for the development of therapies for DMD.

PMID- 24096572
TI  - A controllable approach to development of multi-spectral conjugated polymer
      nanoparticles with increased emission for cell imaging.
AB  - The authors demonstrate a smart and versatile approach for preparing multi
      spectral conjugated polymers from a commercial precursor MEH-PPV without tedious
      synthetic modification. Multi-color CPNs with small size have also been
      successfully prepared using a modified-reprecipitation procedure for live cell
      imaging. 

PMID- 24096573
TI  - Toxoplasma gondii: immune response and protective efficacy induced by ROP16/GRA7
      multicomponent DNA vaccine with a genetic adjuvant B7-2.
AB  - Toxoplasma gondii infection occurs commonly in humans and other warm-blooded
      animals. Its serious impact on public health and livestock sectors makes the
      development of an effective vaccine particularly important. In the current study,
      we constructed a multiantigenic DNA vaccine expressing ROP16 and GRA7 of T.
      gondii and evaluated the protective efficacy of these two fragments with or
      without a plasmid encoding murine costimulatory molecule B7-2. These recombinant
      eukaryotic expression plasmids were termed pROP16, pGRA7, pROP16-GRA7 and pB7-2,
      respectively. After intramuscular immunization in Kunming mice, we assessed the
      immune response using cytokine and antibody determinations, T lymphocyte subsets
      analysis, and the survival times of mice post acute T. gondii challenge. The
      results showed that mice immunized with the multiantigenic DNA vaccine pROP16
      GRA7 gained higher levels of IgG titers and IgG2a subclass titers, production of
      IFN-gamma, percentage of CD8+ T cells and median survival times against the acute
      infection of T. gondii compared with those of mice administered with pROP16 or
      pGRA7 and those in control groups. Moreover, the adjuvant pB7-2 formulated with
      DNA vaccine boosted these humoral and cellular (Th1, CD8+ T cell) immune
      responses. Therefore, it might be a promising genetic adjuvant to DNA vaccine
      against T. gondii for further investigation.

PMID- 24096574
TI  - Macrophage migration inhibitory factor for the early prediction of infarct size.
AB  - BACKGROUND: Early diagnosis and knowledge of infarct size is critical for the
      management of acute myocardial infarction (MI). We evaluated whether early
      elevated plasma level of macrophage migration inhibitory factor (MIF) is useful
      for these purposes in patients with ST-elevation MI (STEMI). METHODS AND RESULTS:
      We first studied MIF level in plasma and the myocardium in mice and determined
      infarct size. MI for 15 or 60 minutes resulted in 2.5-fold increase over control
      values in plasma MIF levels while MIF content in the ischemic myocardium reduced
      by 50% and plasma MIF levels correlated with myocardium-at-risk and infarct size
      at both time-points (P < 0.01). In patients with STEMI, we obtained admission
      plasma samples and measured MIF, conventional troponins (TnI, TnT), high
      sensitive TnI (hsTnI), creatine kinase (CK), CK-MB, and myoglobin. Infarct size
      was assessed by cardiac magnetic resonance (CMR) imaging. Patients with chronic
      stable angina and healthy volunteers were studied as controls. Of 374 STEMI
      patients, 68% had elevated admission MIF levels above the highest value in
      healthy controls (> 41.6 ng/mL), a proportion similar to hsTnI (75%) and TnI
      (50%), but greater than other biomarkers studied (20% to 31%, all P < 0.05 versus
      MIF). Only admission MIF levels correlated with CMR-derived infarct size,
      ventricular volumes and ejection fraction (n = 42, r = 0.46 to 0.77, all P <
      0.01) at 3 day and 3 months post-MI. CONCLUSION: Plasma MIF levels are elevated
      in a high proportion of STEMI patients at the first obtainable sample and these
      levels are predictive of final infarct size and the extent of cardiac remodeling.

PMID- 24096575
TI  - Physician accuracy in interpreting potential ST-segment elevation myocardial
      infarction electrocardiograms.
AB  - BACKGROUND: With adoption of telemedicine, physicians are increasingly asked to
      diagnose ST-segment elevation myocardial infarctions (STEMIs) based on
      electrocardiograms (ECGs) with minimal associated clinical information. We sought
      to determine physicians' diagnostic agreement and accuracy when interpreting
      potential STEMI ECGs. METHODS AND RESULTS: A cross-sectional survey was performed
      consisting of 36 deidentified ECGs that had previously resulted in putative STEMI
      diagnoses. Emergency physicians, cardiologists, and interventional cardiologists
      participated in the survey. For each ECG, physicians were asked, "based on the
      ECG above, is there a blocked coronary artery present causing a STEMI?" The
      reference standard for ascertaining the STEMI diagnosis was subsequent emergent
      coronary arteriography. Responses were analyzed with generalized estimating
      equations to account for nested and repeated measures. One hundred twenty-four
      physicians interpreted a total of 4392 ECGs. Among all physicians, interreader
      agreement (kappa) for ECG interpretation was 0.33, reflecting poor agreement. The
      sensitivity to identify "true" STEMIs was 65% (95% CI: 63 to 67) and the
      specificity was 79% (95% CI: 77 to 81). There was a 6% increase in the odds of
      accurate ECG interpretation for every 5 years of experience since medical school
      graduation (OR 1.06, 95% CI: 1.02 to 1.10, P = 0.01). After adjusting for
      experience, there was no significant difference in the odds of accurate
      interpretation by specialty-Emergency Medicine (reference), General Cardiology
      (AOR 0.97, 95% CI: 0.79 to 1.2, P = 0.80), or Interventional Cardiology
      physicians (AOR 1.24, 95% CI: 0.93 to 1.7, P = 0.15). CONCLUSIONS: There is
      significant physician disagreement in interpreting ECGs with features concerning
      for STEMI. Such ECGs lack the necessary sensitivity and specificity to act as a
      suitable "stand-alone" diagnostic test.

PMID- 24096576
TI  - Human ovarian tissue cortex surrounding benign and malignant lesions.
AB  - OBJECTIVE: To quantify the number of follicles in patients with ovarian
      pathologies, benign and malignant, in pregnant and nonpregnant states and to
      determine how the presence of ovarian masses and BRCA status affects follicular
      counts. MATERIALS AND METHODS: Slides from 134 reproductive-aged women undergoing
      oophorectomy were examined using light microscopy by 3 independent counters
      blinded to the diagnosis. In all, 20 patients had cancer, 69 had benign
      conditions, and 35 patients were BRCA+ or had a strong family history of breast
      and/or ovarian cancer. In all, 10 women were either pregnant or immediately
      postpartum. RESULTS: Patients undergoing risk-reducing surgery had significantly
      decreased follicle count compared to physiologic control. Patients with cancer
      had significantly decreased counts compared to all other groups. There were no
      differences within the benign cohort. CONCLUSIONS: When compared to benign
      masses, the cortex surrounding an ovarian malignancy has decreased follicle
      density. The stretch impact may minimize any impact on total follicle numbers.
      Furthermore, there may be a proliferation of ovarian stroma, with the same number
      of follicles spread over a larger surface area. This information is important
      when counseling women with ovarian masses regarding the use of ovarian tissue
      cryopreservation.

PMID- 24096577
TI  - Watching DNA breath one molecule at a time.

PMID- 24096578
TI  - Neural tuning of human face processing.

PMID- 24096579
TI  - Revealing what gets buried first in protein folding.

PMID- 24096580
TI  - Using molecular dynamics to elucidate the structural basis for function in
      pLGICs.

PMID- 24096581
TI  - The association between the Arg280His polymorphism in the XRCC1 gene and the risk
      of hematological malignancies.
AB  - The associations between the Arg280His polymorphism in X-ray repair cross
      complementing gene 1 (XRCC1 gene) and hematological malignancies have been
      extensively investigated. However, the results were inconsistent. The objective
      of the current study was to investigate the associations between the Arg280His
      polymorphism in XRCC1 gene and the risk of hematological malignancies by meta
      analysis. We searched PubMed, Embase, CNKI, Wanfang, and Weipu databases,
      covering all studies until 07 Aug 2013. Statistical analysis was performed by
      using the Revman4.2 software and the Stata10.0 software. A total of 2,650 cases
      and 3,856 controls in 12 case-control studies concerning the Arg280His
      polymorphism were included. The results suggested that the Arg280His polymorphism
      might not be associated with risk of hematological malignancies (OR = 1.08, 95%CI
      = 0.86-1.35, P = 0.50). In the subgroup analyses by cancer types and ethnicity,
      no significant associations were found among different cancers or different
      ethnicities. The current meta-analysis indicated that the Arg280His polymorphism
      in the XRCC1 gene might not be a risk factor for hematological malignancies. In
      future, more large-scale case-control studies are needed to validate these
      results.

PMID- 24096582
TI  - Silencing of GLS and overexpression of GLS2 genes cooperate in decreasing the
      proliferation and viability of glioblastoma cells.
AB  - Glutamine (Gln) metabolism, initiated by its degradation by glutaminases (GA), is
      elevated in neoplastic cells and tissues. In malignant glia-derived tumors, GA
      isoforms, KGA and GAC, coded by the GLS gene, are overexpressed, whereas the GLS2
      coded GAB and LGA isoforms, are hardly detectable in there. Our previous study
      revealed that transfection of T98G glioblastoma cells with GAB reduced cell
      proliferation and migration, by a yet unknown mechanism not related to Gln
      degradation. The question arose how simultaneous overexpression of GAB and
      inhibition of KGA would affect glioblastoma cell growth. Here, we used siRNA to
      silence the expression of Gls in T98G cells which were or were not stably
      transfected with GAB (TGAB cells). In both T98G and TGAB cell lines, silencing of
      Gls with siRNAs targeted at different sequences decreased cell viability and
      proliferation in a different, sequence-dependent degree, and the observed
      decreases were in either cell line highly correlated with increase of
      intracellular Gln (r > 0.9), a parameter manifesting decreased Gln degradation.
      The results show that combination of negative modulation of GA isoforms arising
      from GLS gene with the introduction of the GLS2 gene product, GAB, may in the
      future provide a useful means to curb glioblastoma growth in situ. At the same
      time, the results underscore the critical role of Gln degradation mediated by KGA
      in the manifestations of aggressive glial tumor phenotype. 

PMID- 24096583
TI  - Letter regarding Li et al. entitled "Quantitative assessment of the association
      between CYP1A1 A4889G polymorphism and endometrial cancer risk".

PMID- 24096584
TI  - Mutation and protein expression analysis of CYP1A1 gene-a study on female breast
      cancer cases from India.
AB  - Increased risk may be associated with exposure to genotoxic agents during breast
      development because the undifferentiated ductal elements of breast are more
      susceptible to the action of genotoxic early in life and thus an impairment in
      Cytochrome P 4501A1 (CYP1A1) may contribute to the development of breast cancer.
      Therefore, we carried out the population-based study in a total of 105 Indian
      female breast cancer cases with equal normal adjacent controls. A total of 20
      samples (20/105, 19.04 %) showed final mutations in the exon 7 of the CYP1A1 gene
      where 5 cases harbored frame shift mutation (deletion of G nucleotide), and the
      remaining were missense mutation observed in 15 cases of breast cancer with
      significant association to histological grade (chi square -7.20, p = 0.02), tumor
      stage (chi square -6.36, p = 0.01), menopausal stage (chi square -9.76, p =
      0.001), and ER status (chi square -4.22, p = 0.03). We further did protein
      expression analysis of CYP1A1 through immunohistochemistry where 66 cases showed
      down or no expression (+) (66/105, 62.85 %), 28 cases with moderate expression
      (++) (28/105, 26.66 %), and 11 cases with high expression (+++) (11/105, 10.47
      %). Highly significant associations were observed between protein expression and
      clinico-pathological variables like Her 2 category (chi square = 31.73, p <
      0.0001) and tumor stage (chi square = 10.27, p = 0.005). Importantly, mutation(s)
      of the type like deletion of A nucleotide and missense mutation (Gly > Val)
      exclusively showed low (+) or no expression for the CYP1A1 protein when studied
      in relation to each other. In summary, CYP1A1 may be associated with breast
      cancer and its down regulation may serve as an important tool in the field of
      biomarker study. 

PMID- 24096585
TI  - Anti-anaemia efficacy of beta-lactoglobulin hydrolysate-iron complex on iron
      deficient anaemic rats.
AB  - PURPOSE: The effects of orally administered beta-lactoglobulin hydrolysate-iron
      complex (beta-LGH-Fe) on haematological and biochemical parameters in anaemic
      rats were evaluated. Female weaning Sprague-Dawley rats were fed with iron
      deficient diet to induce iron deficiency anaemia. After 6 weeks, the obtained
      anaemic rats were divided into five groups: iron deficiency control group (iron
      deficient diet without beta-LGH-Fe complex supplementation, IDC); three groups
      supplemented with different dosages of beta-LGH-Fe complex (0.5 mg Fe/kg BW, iron
      deficient diet with low beta-LGH-Fe, IDLFe; 2.0 mg Fe/kg BW, iron-deficient diet
      with medium beta-LGH-Fe, IDMF; 4.0 mg Fe/kg BW, iron-deficient diet with high
      beta-LGH-Fe, IDHFe); and ferrous sulphate-supplemented group at a dosage of 2.0
      mg Fe/kg BW. RESULTS: beta-LGH-Fe complex could significantly improve hematocrit
      and haemoglobin decrease, and normalise the serum iron level, total iron-binding
      capacity and transferrin saturation of anaemic rats in a dose-dependent manner.
      Serum ferritin content and hepatic nonheme iron level were also increased. In
      addition, the antioxidant enzyme activities of superoxidase dismutase, catalase
      and glutathione peroxidase in both plasma and liver homogenate were improved. The
      production of malondialdehyde and pro-inflammatory cytokines (TNF-alpha and IL-6)
      decreased. CONCLUSIONS: It suggests that beta-LGH-Fe complex can ameliorate iron
      deficiency anaemia, which might make it a potential ingredient with anti-anaemia
      activity.

PMID- 24096587
TI  - Rational syntheses of core-shell Fex@Pt nanoparticles for the study of
      electrocatalytic oxygen reduction reaction.
AB  - We report on the syntheses of core-shell Fex@Pt (x=0.4-1.2) nanoparticles (NPs)
      with Pt-shell thickness systematically controlled while the overall particle size
      is constant. The syntheses were achieved via one-pot ultrasound-assisted polyol
      synthesis (UPS) reactions. Fe1.2@Pt showed a record-breaking high core-element
      content (55 at%) of core-shell NPs. Based on observations from a series of
      control experiments, we propose a mechanism of the NPs' formation that enables
      control of shell thickness in UPS reactions. Fex@Pt NPs showed drastic
      enhancements in mass and specific activity for oxygen reduction reaction (ORR)
      and significantly enhanced durability compared to commercial Pt NPs. Fex@Pt with
      a 1 (monolayer) ML Pt shell showed the highest activity. The ab initio density
      functional theory calculations on the binding energies of oxygen species on the
      surfaces of Fex@Pt NPs showed that the 1 ML case is most favourable for the ORR,
      and in good agreement with the experimental results.

PMID- 24096586
TI  - Diet-induced obese rats have higher iron requirements and are more vulnerable to
      iron deficiency.
AB  - PURPOSE: Since obesity is associated with poorer iron status, the effects of diet
      induced obesity on iron status and iron-regulatory pathways were examined.
      METHODS: Weanling male diet-induced obese sensitive (n = 12/diet group) and
      resistant (n = 12/diet group) rats were fed one of four high-fat, high-energy
      diets supplemented with 5 (5Fe, low), 15 (15Fe, marginal), 35 (35Fe, normal) or
      70 (70Fe, high) mg iron/kg diet for 12 weeks. At the end of the study, rats in
      each diet group were categorised as obese (>19 %) or lean (<17 %) based on
      percentage body fat. RESULTS: Obese rats gained more weight, had larger total
      lean mass, consumed more food and showed greater feed efficiency compared with
      lean rats. Obese rats fed the 5Fe and 15Fe diets had poorer iron status than lean
      rats fed the same diet. Obese 5Fe rats had lower serum iron and more severe iron
      deficiency anaemia. Obese 15Fe rats had lower mean corpuscular haemoglobin and
      liver iron concentrations. Hepcidin mRNA expression in liver and adipose tissue
      was similar for obese and lean rats. Iron concentration and content of the iron
      transporters divalent metal transporter 1 and ferroportin 1 in duodenal mucosa
      were also similar. CONCLUSIONS: Obese rats that were larger, regardless of
      adiposity, had higher iron requirements compared with lean rats that appeared
      independent of hepcidin, inflammation and intestinal iron absorption. Higher iron
      requirements may have resulted from larger accretion of body mass and blood
      volume. Greater food consumption did not compensate for the higher iron needs,
      indicating increased susceptibility to iron deficiency.

PMID- 24096588
TI  - The role of anticipatory postural adjustments in interlimb coordination of
      coupled arm movements in the parasagittal plane: III. difference in the energy
      cost of postural actions during cyclic flexion-extension arm movements, ISO- and
      ANTI-directionally coupled.
AB  - When oscillating the upper limbs together in the parasagittal plane, movements
      coordination is lower (i.e., variability of the interlimb relative phase is
      higher) in antidirectional (ANTI) than in isodirectional (ISO) coupling. In
      contrast, we previously observed that for arm movements in the horizontal plane,
      the coordination was worse in ISO than ANTI and the energetic cost of postural
      activities was higher in ISO. Having hypothesised that the higher postural cost
      was one factor responsible for the coordination deficit in horizontal ISO, we
      measured the oxygen uptake ([Formula: see text]) in parasagittal movements,
      expecting that in this case too, the postural cost is higher in the less
      coordinated mode (ANTI). Breath-by-breath metabolic ([Formula: see text],
      [Formula: see text]) and cardiorespiratory (HR, [Formula: see text]) parameters
      were measured in seven participants, who performed cyclic flexions-extensions in
      the parasagittal plane with either one arm or both arms, in ISO or ANTI coupling
      and at 1.4, 2.2 and 2.6 Hz. In each condition, the intermittent exercise (12 s
      movement, 12 s rest) lasted 264 s. A force platform recorded the mechanical
      actions to the ground. The exercise metabolic cost ([Formula: see text]) was
      found to be significantly higher in parasagittal ANTI than ISO. The movement
      amplitude being equal in the two modes, the ANTI-ISO difference should be
      ascribed to postural activities. This would confirm that the less-coordinated
      coupling mode requires the higher postural effort in parasagittal movements too.
      When rising the movement frequency, [Formula: see text] increased and linearly
      correlated with the coordination loss. Comparison of parasagittal with horizontal
      movements showed that [Formula: see text] was lower in parasagittal ANTI than in
      horizontal ISO (the less-coordinated modes), while it was not different between
      parasagittal ISO and horizontal ANTI (the more-coordinated modes). 

PMID- 24096591
TI  - The European Union physical agents (electromagnetic fields) directive: an update
      for the MRI community.

PMID- 24096590
TI  - SPECT-CT: applications in musculoskeletal radiology.
AB  - This article reviews the technique, basic science principles and applications of
      integrated single photon emission CT (SPECT)-CT in musculoskeletal radiology. A
      review of the current evidence on the topic was undertaken, and selected clinical
      cases from the authors' institution have been used for illustration. SPECT-CT is
      a technology with emerging applications that offers technical advantages to image
      fusion of separately acquired SPECT and CT studies. The prevailing evidence
      indicates that there may be benefit in adding SPECT-CT to conventional imaging
      algorithms during the evaluation of some malignant and benign musculoskeletal
      conditions. SPECT-CT can improve both sensitivity and specificity by reducing
      equivocal interpretation in comparison to planar scintigraphy or SPECT alone. The
      evidence base for SPECT-CT in musculoskeletal radiology is still evolving. There
      is a lack of evidence comparing SPECT-CT with MRI in many key indications, and
      further research is required in these areas. 

PMID- 24096593
TI  - An electrostatic model for the determination of magnetic anisotropy in dysprosium
      complexes.
AB  - Understanding the anisotropic electronic structure of lanthanide complexes is
      important in areas as diverse as magnetic resonance imaging, luminescent cell
      labelling and quantum computing. Here we present an intuitive strategy based on a
      simple electrostatic method, capable of predicting the magnetic anisotropy of
      dysprosium(III) complexes, even in low symmetry. The strategy relies only on
      knowing the X-ray structure of the complex and the well-established observation
      that, in the absence of high symmetry, the ground state of dysprosium(III) is a
      doublet quantized along the anisotropy axis with an angular momentum quantum
      number mJ=+/-(15)/2. The magnetic anisotropy axis of 14 low-symmetry monometallic
      dysprosium(III) complexes computed via high-level ab initio calculations are very
      well reproduced by our electrostatic model. Furthermore, we show that the
      magnetic anisotropy is equally well predicted in a selection of low-symmetry
      polymetallic complexes.

PMID- 24096592
TI  - Detection of ischaemic myocardial lesions with coronary CT angiography and
      adenosine-stress dynamic perfusion imaging using a 128-slice dual-source CT:
      diagnostic performance in comparison with cardiac MRI.
AB  - OBJECTIVE: We assessed the diagnostic performance of adenosine-stress dynamic CT
      perfusion (ASDCTP) imaging and coronary CT angiography (CCTA) for the detection
      of ischaemic myocardial lesions using 128-slice dual-source CT compared with that
      of 1.5 T cardiac MRI. METHODS: This prospective study included 33 patients (61+/
      8 years, 82% male) with suspected coronary artery diseases who underwent ASDCTP
      imaging and adenosine-stress cardiac MRI. Two investigators independently
      evaluated ASDCTP images in correlation with significant coronary stenosis on CCTA
      using two different thresholds of 50% and 70% diameter stenosis. Hypoattenuated
      myocardial lesions on ASDCTP associated with significant coronary stenoses on
      CCTA were regarded as true perfusion defects. All estimates of diagnostic
      performance were calculated and compared with those of cardiac MRI. RESULTS: With
      use of a threshold of 50% diameter stenosis on CCTA, the diagnostic estimates per
      myocardial segment were as follows: sensitivity, 81% [95% confidence interval
      (CI): 70-92%]; specificity, 94% (95% CI: 92-96%); and accuracy 93% (95% CI: 91
      95%). With use of a threshold of 70%, the diagnostic estimates were as follows:
      sensitivity, 48% (95% CI: 34-62%); specificity, 99% (95% CI: 98-100%); and
      accuracy, 94% (95% CI: 92-96%). CONCLUSION: Dynamic CTP using 128-slice dual
      source CT enables the assessment of the physiological significance of coronary
      artery lesions with high diagnostic accuracy in patients with clinically
      suspected coronary artery disease. ADVANCES IN KNOWLEDGE: Combined CCTA and
      ASDCTP yielded high accuracy in the detection of perfusion defects regardless of
      the threshold of significant coronary stenosis.

PMID- 24096594
TI  - Confidence bands for the difference between two median survival times as a
      function of covariates.
AB  - In this paper, the estimation of the difference between two median survival times
      is considered when two treatment groups of right-censored data and the associated
      covariates are available. To identify the possible range of covariates over which
      the two treatments would produce different median survival times, two confidence
      bands for the difference as a function of the covariates are proposed under the
      stratified and treatment-specific Cox models, respectively. The results of a
      simulation study indicate that the latter generally maintains its confidence
      level and the former holds its confidence level and preserves a narrower width
      when the two treatments satisfy the stratified Cox model. An application of the
      proposed confidence bands is finally illustrated with a data set in a two-arm
      lung cancer study. 

PMID- 24096595
TI  - Cardiovascular control and stabilization via inclination and mobilization during
      bed rest.
AB  - Cardiovascular deconditioning has long been recognized as a characteristic of the
      physiological adaptation to long-term bed rest in patients. The process is
      thought to contribute to orthostatic intolerance and enhance secondary
      complications in a significant way. Mobilization is a cost-effective and simple
      method to maintain the cardiovascular parameters (i.e., blood pressure, heart
      rate) stable, counter orthostatic intolerance and reduce the risk of secondary
      problems in patients during long-term immobilization. The aim of this project is
      to control the cardiovascular parameters such as heart rate and blood pressure of
      bed rest patients via automated leg mobilization and body tilting. In a first
      step, a nonlinear model predictive control strategy was designed and evaluated on
      five healthy subjects and 11 bed rest patients. In a next step, a clinically
      feasible study was conducted on two patients. The mean values differed on average
      less than 1 bpm from the predetermined heart rate and less than 2.5 mmHg from the
      desired blood pressure values. These results of the feasibility study are
      promising, although heterogeneous disease etiologies and individual medication
      strongly influence the mechanically induced reactions. The long-term goal is an
      automation of the control of physiological signals and the mobilization of bed
      rest patients in an early phase of the rehabilitation process. Therefore, this
      new approach could help to strengthen the cardiovascular system and prevent
      secondary health problems arising from long-term bed rest.

PMID- 24096596
TI  - Syphilis diagnosis: three cases with increasing treponemal test result after
      therapy.

PMID- 24096597
TI  - Paracorporeal ventricular assist device as a bridge to transplant candidacy in
      the era of implantable continuous-flow ventricular assist device.
AB  - Ventricular assist devices (VADs) have long been used as bridge to transplant
      therapy (BTT). Nipro-Toyobo paracorporeal pulsatile-flow VAD (nt-VAD) was the
      only device available until April 2011, when implantable continuous-flow VADs (cf
      VADs) became available. Although cf-VADs are central to BTT, nt-VAD remains a
      necessary option. We aimed to clarify the role of nt-VAD in an era of increasing
      cf-VAD use. We retrospectively reviewed patients who underwent VAD implantation
      at the National Cerebral and Cardiovascular Center from May 2011 to March 2013.
      Characteristics were compared between the nt-VAD and cf-VAD groups. Twenty-nine
      patients (mean age 37.7 +/- 11.1 years, 23 males) underwent VAD implantation.
      Fifteen patients initially received nt-VADs, although 4 were converted to cf
      VADs. Of these 15 patients, 3 were too small for cf-VADs and 2 needed bilateral
      ventricular support. The remaining 10 patients received nt-VADs (7 patients at
      INTERMACS level 1 and 3 at level 2). The nt-VAD group patients had significantly
      more preoperative mechanical circulatory support and were in a more critical
      condition before VAD implantation than the cf-VAD group. The 2-year survival rate
      was not significantly different. Despite the critical conditions of nt-VAD
      patients, their overall survival is not statistically inferior to that of cf-VAD
      patients. nt-VAD is a good option as a BTC for the patient with urgent and
      critical condition.

PMID- 24096598
TI  - Assessment of pulmonary toxicity of MgO nanoparticles in rats.
AB  - In this study, we have evaluated the pulmonary toxicity of MgO nanoparticles (MgO
      NPs) in rats following their exposure. NPs in phosphate buffered saline + 1%
      Tween 80 were exposed via intratracheal instillation at a doses of 1 mg/kg or 5
      mg/kg into rat lungs and evaluated for various tissue damage markers like
      alkaline phosphatase (ALP) and lactate dehydrogenase (LDH) in bronchoalveolar
      lavage (BAL) fluid and histopathology of lungs at 1, 7, and 30 days of post
      exposure intervals. A dose-dependant increase in ALP and LDH activity was
      observed in BAL fluids of rat lungs than sham control at all post-exposure
      periods (P <0.05), and a dose-dependant infiltration of interstitial lymphocytes,
      peribronchiolar lymphocytic infiltration, and dilated and/or congested vessels at
      1 day post-exposure period, worsened at 1 week period, and were reduced at 1
      month at histology, indicating the pulmonary toxicity of MgO NPs. In conclusion,
      MgO NPs exposure produced a dose-dependent pulmonary toxicity in rats and was
      comparable with that of Quartz particles.

PMID- 24096599
TI  - Bridging communication gaps with the deaf.

PMID- 24096600
TI  - Hepatitis goes viral.

PMID- 24096601
TI  - Pharmacokinetic-pharmacodynamic modeling of the anticancer effect of erlotinib in
      a human non-small cell lung cancer xenograft mouse model.
AB  - AIM: Erlotinib is used to treat non-small-cell lung cancer (NSCLC), which targets
      epidermal growth factor receptor (EGFR) tyrosine kinase. The aim of this study
      was to investigate the relationship between erlotinib plasma concentrations and
      phosphorylated EGFR (pEGFR) levels, as well as the relationship between pEGFR
      levels and tumor growth inhibition in a human non-small-cell lung cancer
      xenograft mouse model. METHODS: Female BALB/c nude mice were implanted with the
      human NSCLC cell line SPC-A-1. The animals were given via gavage a single dose of
      erlotinib (4, 12.5, or 50 mg/kg). Pharmacokinetics of erlotinib was determined
      using LC-MS/MS. Tumor volume and pEGFR levels in tumor tissues were measured at
      different time points after erlotinib administration. The levels of pEGFR in
      tumor tissues was detected using Western blotting and ELISA assays. RESULTS: The
      pharmacokinetics of erlotinib was described by a two-compartment model with first
      order extravascular absorption kinetics. There was a time delay of approximately
      2 h between erlotinib plasma concentrations and pEGFR degradation. The time
      course of pEGFR degradation was reasonably fit by the indirect response model
      with a calculated IC50 value of 1.80 MUg/mL. The relationship between pEGFR
      levels and tumor volume was characterized by the integrated model with a Kbio
      value of 0.507 cm(3)/week, which described the impact of pEGFR degradation on
      tumor growth. CONCLUSION: The pharmacokinetic/pharmacodynamic properties of
      erlotinib in a human tumor xenograft model were described by the indirect
      response model and integrated model, which will be helpful in understanding the
      detailed processes of erlotinib activity and determining an appropriate dosing
      regimen in clinical studies.

PMID- 24096602
TI  - Claulansine F promotes neuritogenesis in PC12 cells via the ERK signaling
      pathway.
AB  - AIM: To study the effects of Claulansine F (Clau F), a carbazole alkaloid
      isolated from the stem of Clausena lansium (Lour) Skeels, on neuritogenesis of
      PC12 cells, and to elucidate the mechanism of action. METHODS: Neuritogenesis of
      PC12 cells was quantified under an inverted microscope. Expression of the neurite
      outgrowth marker GAP-43 was detected using immunofluorescence. GAP-43
      transcription was measured using RT-PCR. Cell viability was evaluated with MTT
      assay. The levels of phosphor-ERK1/2, phosphor-CREB, phosphor-AKT and acetylate
      p53 in the cells were examined using Western blotting analyses. RESULTS: Clau F
      (10-100 MUmol/L) significantly increased the percentage of PC12 cells bearing
      neurites. Clau F markedly increased the expression of GAP-43 in the cells. The
      efficiency of Clau F (10 MUmol/L) in increasing neuritogenesis and GAP-43
      expression was comparable to that of nerve growth factor (50 ng/mL). In addition,
      Clau F completely blocked the proliferation of PC12 cells within 7 d of
      incubation, whereas it did not cause cell death in cultured rat cortical neurons.
      Treatment of PC12 cells with Clau F activated both ERK and AKT signaling
      pathways. Co-treatment of PC12 cells with the specific ERK inhibitor PD98059, but
      not the specific PI3K inhibitor LY294002, blocked Clau F-induced neuritogenesis
      and GAP-43 upregulation. CONCLUSION: Clau F promotes neuritogenesis in PC12 cells
      specifically via activation of the ERK signaling pathway.

PMID- 24096603
TI  - Endovenous thermal ablation for healing venous ulcers and preventing recurrence.
AB  - BACKGROUND: Venous leg ulcers represent the worst extreme within the spectrum of
      chronic venous disease. Affecting up to 3% of the adult population, this
      typically chronic, recurring condition significantly impairs quality of life, and
      its treatment places a heavy financial burden upon healthcare systems. The
      current mainstay of treatment for venous leg ulcers is compression therapy, which
      has been shown to enhance ulcer healing rates. Open surgery on the veins in the
      leg has been shown to reduce ulcer recurrence rates, but it is an unpopular
      option and many patients are unsuitable. The efficacy of the newer, minimally
      invasive endovenous thermal techniques has been established in uncomplicated
      superficial venous disease, and these techniques are now beginning to be used in
      the management of venous ulceration, though the evidence for this treatment is
      currently unclear. It is hypothesised that, when used with compression, ablation
      may further reduce pressures in the leg veins, resulting in improved rates of
      healing. Furthermore, since long-term patient concordance with compression is
      relatively poor, it may prove more popular, effective and cost-effective to
      provide a single intervention to reduce recurrence, rather than life-long
      treatment with compression. OBJECTIVES: To determine the effects of superficial
      endovenous thermal ablation on the healing, recurrence and quality of life of
      people with active or healed venous ulcers. SEARCH METHODS: In August 2013 we
      searched Cochrane Wounds Group Specialised Register; The Cochrane Central
      Register of Controlled Trials (CENTRAL) (The Cochrane Library); Ovid MEDLINE;
      Ovid MEDLINE (In-Process & Other Non-Indexed Citations); Ovid EMBASE; and EBSCO
      CINAHL. There were no restrictions on the language of publication but there was a
      date restriction based on the fact that superficial endovenous thermal ablation
      is a comparatively new medical technology. SELECTION CRITERIA: Randomised
      clinical trials comparing endovenous thermal ablative techniques with compression
      therapy alone for venous leg ulcers were eligible for inclusion. Trials had to
      report on at least one objective measure of ulcer healing (primary outcome) such
      as proportion of ulcers healed at a given time point, time to complete healing,
      change in ulcer size, proportion of ulcers recurring over a given time period, or
      at a specific point, and ulcer-free days. Secondary outcomes sought included
      patient-reported quality of life, economic data and adverse events. DATA
      COLLECTION AND ANALYSIS: Details of potentially eligible studies were extracted
      and summarised using a data extraction table. Data extraction and validity
      assessment were performed independently by two review authors, and any
      disagreements resolved by consensus or by arbitration of a third review author.
      MAIN RESULTS: No eligible randomised controlled trials were identified. There is
      an absence of evidence regarding the effects of superficial endovenous thermal
      ablation on ulcer healing, recurrence or quality of life of people with venous
      leg ulcer disease. AUTHORS' CONCLUSIONS: The review identified no randomised
      controlled trials on the effects on ulcer healing, recurrence or quality of life,
      of superficial endovenous thermal ablation in people with active or healed venous
      leg ulcers. Adequately-powered, high quality randomised controlled trials
      comparing endovenous thermal ablative interventions with compression therapy are
      urgently required to explore this new treatment strategy. These should measure
      and report outcomes that include time to ulcer healing, ulcer recurrence, quality
      of life and cost-effectiveness.

PMID- 24096604
TI  - Comments on potential efficacy of monthly administrations of spot-on moxidectin
      2.5%/imidacloprid 10% in the simultaneous prevention of major canine filarioses.
AB  - Information on the efficacy of pharmaceutical protocols for the prevention of the
      major canine filarioses (i.e., Dirofilaria immitis, Dirofilaria repens, and
      Acanthocheilonema reconditum) under natural conditions is scant. Chemoprophylaxis
      for canine filarioses under field conditions deserves to be studied more fully
      and information about vector biology, ecology, and seasonality has to be well
      appreciated to correctly set control protocols. It is advisable that researchers
      planning field trials to assess the efficacy of any product for the prevention of
      canine vector-borne diseases should consider different eco-epidemiological
      aspects of diseases, including their dynamics of transmission, which are driven
      by complex interactions between animals, pathogens, and vectors. 

PMID- 24096605
TI  - Effects of dextran sulfates on the acute infection and growth stages of
      Toxoplasma gondii.
AB  - Toxoplasma gondii is one of the most prevalent parasites, causing toxoplasmosis
      in various warm-blooded animals, including humans. Because of the broad range of
      hosts susceptible to T. gondii, it had been postulated that a universal component
      of the host cell surface, such as glycosaminoglycans (GAGs), may act as a
      receptor for T. gondii infection. Carruthers et al. (Infect Immun 68:4005-4011,
      2000) showed that soluble GAGs have also been shown to disrupt parasite binding
      to human fibroblasts. Therefore, we investigated the inhibitory effect of GAGs
      and their analogue dextran sulfate (DS) on T. gondii infection. For up to 24 h of
      incubation after inoculation of T. gondii, the inhibitory effect of GAGs on T.
      gondii infection and growth inside the host cell was weak. In contrast, DS
      markedly inhibited T. gondii infection. Moreover, low molecular weight DS
      particularly slowed the growth of T. gondii inside host cells. DS10 (dextran
      sulfate MW 10 kDa) was the most effective agent in these in vitro experiments and
      was therefore tested for its inhibitory effects in animal experiments; infection
      inhibition by DS10 was confirmed under these in vivo conditions. In this report,
      we showed that DSs, especially DS10, have the potential of a new type of drug for
      toxoplasmosis. 

PMID- 24096606
TI  - Effect of a novel benzimidazole derivative in experimental Schistosoma mansoni
      infection.
AB  - Currently, praziquantel is the only drug of choice for treatment of
      schistosomiasis. Reports of praziquantel resistance raise concerns about future
      control of the disease. Therefore, the search for new schistosomicidal drugs is
      eminent. In this study, the effect of a novel benzimidazole-derived compound
      (compound BTP-Iso) was assessed in mice harboring adult Schistosoma mansoni
      (Egyptian strain). Mice were treated 42 days p.i. with compound BTP-Iso using two
      treatment regimens (200 or 300 mg/kg). In both regimens, there were significant
      reductions in the number of recovered S. mansoni worms especially females and in
      immature ova, in addition to a significant reduction in the number and size of
      hepatic granulomata. A dose of 300 mg/kg resulted in a significant decrease in
      intestinal and hepatic tissue egg loads. Effect on schistosomes was confirmed by
      scanning electron microscopy, where adult worms recovered from mice treated with
      200 mg/kg of compound BTP-Iso revealed tegumental alternations, characterised by
      swelling of tegumental ridges, bleb formation, and mild erosion in male worms;
      however in females, there were extensive erosion and destruction of the
      tegumental surface. These promising results may encourage future use of compound
      BTP-Iso in the treatment of schistosomiasis. However, more research is needed to
      detect the effect of compound BTP-Iso on early developmental stages of S. mansoni
      and on other species of human schistosomes. 

PMID- 24096607
TI  - Utility of divergent domains of 28S ribosomal RNA in species discrimination of
      paramphistomes (Trematoda: Digenea: Paramphistomoidea).
AB  - Among the digenetic trematodes, paramphistomes are known to be the causative
      agent of "amphistomiasis" or the stomach fluke disease of domestic and wild
      animals, mainly ruminants. The use of 28S (divergent domains) and 18S rRNA for
      phylogenetic inference is significantly warranted for these flukes since it is as
      yet limited to merely the exploration of the second internal transcribed spacer
      (ITS2) region. The present study intended to explore the divergent domains (D1
      D3) of 28S rRNA and simultaneously equate the phylogenetic information with 18S
      rRNA in paramphistomes. Divergence of the 28S rRNA domains was evident amongst
      the divergent (D) domains, where D1 domain emerged as the most variable and D2,
      the most robust domain, since the latter could provide a higher resolution of the
      species. D2 was the only domain that comprised compensatory mutations in the
      helices of its structural constraints; this domain is thus well suited for
      species distinction and may be considered a potential DNA barcode complementary
      to mitochondrial DNA. 28S (D1 + D2 + D3) rRNA provided a significant resolution
      of the taxa corroborating with the taxonomy of these flukes and thus proved to be
      more robust as a phylogenetic marker for lower levels than 18S rRNA. Phylogenetic
      inferences of paramphitomes are still scarcely explored; additional data from
      other taxa belonging to this family may estimate better the biodiversity of these
      flukes. 

PMID- 24096608
TI  - Parasites of wild rabbits (Oryctolagus cuniculus) from an urban area in Germany,
      in relation to worldwide results.
AB  - The European rabbit (Oryctolagus cuniculus) belongs to the most invasive and
      successful mammalian species, which is distributed nearly worldwide. In Europe,
      they inhabit broad parts of the mainland and subsequently reached several
      European islands via anthropogenic diversion. Rabbits can also serve as hosts for
      numerous parasite species. The parasite and pathogen fauna of O. cuniculus have
      been well documented in various European countries, although studies in Germany
      are scarce. Until now, a comprehensive survey combining recent international
      studies over parasite fauna of wild rabbits had not been conducted. We examined
      50 wild rabbits from an urban area near Aachen (Germany) to identify their
      metazoan parasite fauna, and then compared our findings to previous international
      investigations. A total of nine parasite species were isolated consisting of four
      endoparasite species (Cittotaenia denticulata, Graphidium strigosum, Passalurus
      ambiguus, and Trichostrongylus retortaeformis) and five ectoparasite species
      (Cheyletiella parasitivorax, Ixodes ricinus, Leporacarus gibbus, Haemodipsus
      ventricosus, and Spilopsyllus cuniculi). Among the ectoparasites were two
      verifiable human pathogenic species and two potentially pathogenic species. In
      comparison to previous studies, a high number of similarities in composition of
      helminth species fauna were revealed. Furthermore, our results showed partial
      agreement with international surveys in prevalence and mean intensity of the
      parasites C. denticulata, G. strigosum, P. ambiguus, and T. retortaeformis. 

PMID- 24096609
TI  - Distribution of lethal giant larvae (Lgl) protein in the tegument and negative
      impact of siRNA-based gene silencing on worm surface structure and egg hatching
      in Schistosoma japonicum.
AB  - Lethal giant larvae (Lgl) are an evolutionarily conserved tumor suppressor
      present in fungi and animals. It plays an essential role in establishing apical
      basal cell polarity, cell proliferation, differentiation, and tissue
      organization. Here, we report the presence of Lgl gene in the blood fluke
      Schistosoma japonicum (SjLgl) (GenBank: KF246684). SjLgl protein was mainly
      distributed in the unique surface tegument structure by immunofluorescence
      microscopic staining. Using a simple soaking method, a short interfering RNA
      (siRNA)-based RNA interference approach knocked down the expression of SjLgl in
      schistosomula in vitro by up to 89.0%. Moreover, tail vein injection of SjLgl
      siRNA into the infected mice reduced SjLgl mRNA levels in vivo by 48.6-85.3%,
      depending on the duration of treatments. SjLgl-specific siRNA treatment during
      the infection in mice significantly altered the surface structure of adult worm,
      featured by the disappearance or significant reduction of sharp spines on the
      inner all of oral and ventral suckers. The siRNA also reduced the hatching rates
      in eggs produced by treated mice by up to 85.3%. These observations implied that
      Lgl plays an important role in the development of tegument in schistosomes, and
      may be explored as a novel target for developing immuno- and/or small molecule
      based therapeutics to control and treat the infections caused by schistosome and
      other flatworms.

PMID- 24096610
TI  - Fatty acid profiles in Leishmania spp. isolates with natural resistance to nitric
      oxide and trivalent antimony.
AB  - Fatty acids, especially those from phospholipids (PLFA), are essential membrane
      components that are present in relatively constant proportions in biological
      membranes under natural conditions. However, under harmful growth conditions,
      such as diseases, environmental changes, and chemical exposure, the fatty acid
      proportions might vary. If such changes could be identified and revealed to be
      specific for adverse situations, they could be used as biomarkers. Such
      biomarkers could facilitate the identification of virulence and resistance
      mechanisms to particular chemotherapeutic agents. Therefore, specific biomarkers
      could lead to better therapeutic decisions that would, in turn, enhance treatment
      effectiveness. The objective of this study was to compare the fatty acid profiles
      of trivalent antimony and nitric oxide (NO)-resistant and -sensitive Leishmania
      chagasi and Leishmania amazonensis isolates. Fatty acid methyl esters (FAMEs)
      were obtained from total lipids (MIDI), ester-linked lipids (ELFA), and ester
      linked phospholipids (PLFA). FAMEs were analyzed by chromatography and mass
      spectrometry. Species- or resistance-associated differences in FAME profiles were
      assessed by nonmetric multidimensional scaling, multiresponse permutation
      procedures, and indicator species analyses. The isolate groups had different MIDI
      FAME profiles. However, neither the ELFA nor PLFA profiles differed between the
      sensitive and resistant isolates. Levels of the fatty acid 18:1 Delta9c were
      increased in sensitive isolates (p < 0,001), whereas the fatty acid 20:4
      Delta5,8,11,14 showed the opposite trend (p < 0.01). We conclude that these two
      fatty acids are potential biomarkers for NO and antimony resistance in L. chagasi
      and L. amazonensis and that they could be helpful in therapeutic diagnoses.

PMID- 24096611
TI  - Myxobolus ophiocarae sp. n. (Myxozoa: Myxosporea: Bivalvulida) infecting the gill
      of wild goby, Ophiocara porocephala (Perciformes: Gobioidei) in Malaysia.
AB  - The authors studied the myxosporean infection of wild gobiid fishes (Perciformes:
      Gobioidei) in the Merang Estuary of Terengganu, Malaysia, and described Myxobolus
      ophiocarae sp. n. in Ophiocara porocephala. Several myxosporean plasmodia were
      found intralamellarly within the gill filaments. The spores differed from those
      of other Myxobolus species previously recorded on gobiid fishes. They were round
      in valvular view and lens-shaped in sutural view, and had two equal-sized,
      pyriform polar capsules with polar filaments having six to seven turns. The
      spores measured 10.34 * 8.79 * 4.53 MUm. The 18S rDNA sequence of M. ophiocarae
      sp. n., based on a contiguous sequence of 1,789 base pairs, differed from any
      other Myxobolus spp. in GenBank. Phylogenetic analysis of the 18S rDNA gene
      revealed that this species showed the closest similarity to Myxobolus
      nagaraensis, Myxobolus lentisuturalis, and Myxobolus cultus.

PMID- 24096612
TI  - A novel system for studying mechanical strain waveform-dependent responses in
      vascular smooth muscle cells.
AB  - While many studies have examined the effects mechanical forces on vSMCs, there is
      a limited understanding of how the different arterial strain waveforms that occur
      in disease and different vascular beds alter vSMC mechanotransduction and
      phenotype. Here, we present a novel system for applying complex, time-varying
      strain waveforms to cultured cells and use this system to understand how these
      waveforms can alter vSMC phenotype and signaling. We have developed a highly
      adaptable cell culture system that allows the application of mechanical strain to
      cells in culture and can reproduce the complex dynamic mechanical environment
      experienced by arterial cells in the body. Using this system, we examined whether
      the type of applied strain waveform altered phenotypic modulation of vSMCs by
      mechanical forces. Cells exposed to the brachial waveform had increased
      phosphorylation of AKT, EGR-1, c-Fos expression and cytoskeletal remodeling in
      comparison to cells treated with the aortic waveform. In addition, vSMCs exposed
      to physiological waveforms had adopted a more differentiated phenotype in
      comparison to those treated with static or sinusoidal cyclic strain, with
      increased expression of vSMC markers desmin, calponin and SM-22 as well as
      increased expression of regulatory miRNAs including miR-143, -145 and -221. Taken
      together, our studies demonstrate the development of a novel system for applying
      complex, time-varying mechanical forces to cells in culture. In addition, we have
      shown that physiological strain waveforms have powerful effects on vSMC
      phenotype. 

PMID- 24096613
TI  - Purified culture systems for bovine oviductal stromal cells.
AB  - Isolated stromal cells from the ampullary and isthmic parts of bovine oviductal
      tissues were cultured in monolayer and spheroid (cell aggregate) systems.
      Prostaglandin F2alpha (PGF) plays a crucial role in oviductal contraction and is
      produced by oviductal epithelial cells in cattle. Since stromal cells of many
      organs produce PGF, PGF production by bovine oviductal stromal cells was
      investigated. After PGF synthesis was confirmed, the utility of isolation and
      culture methods for oviductal stromal cells was evaluated by PGF production in
      the present study. The homogeneity of the cells was > 99%. PGF production of the
      cells was increased by tumor necrosis factor-alpha. The stromal cells aggregated
      and formed a spheroid by the treatments with several reagents. PGF production was
      higher in the spheroid culture than in the monolayer culture. The isolation and
      culture methods described here will facilitate studies of the physiological
      function of bovine oviductal stromal cells. 

PMID- 24096614
TI  - The first one-pot synthesis of a chiral pentakis-adduct of C60 utilising an
      opened-structure malonate tether.
AB  - A pentakis-adduct of C60 with an incomplete octahedral addition pattern was
      synthesised via a one-pot procedure using a tether equipped with five malonate
      moieties. The five-fold Bingel cyclopropanation of C60 was completely
      regioselective and afforded a chiral, C2-symmetric pentakis-adduct which was
      easily separated by column chromatography on SiO2. 

PMID- 24096615
TI  - Cessation of oral anticoagulation in relation to mortality and the risk of
      thrombotic events in patients with atrial fibrillation.
AB  - Bleeding risk (often perceived, rather than actual) is a common reason for
      cessation of oral anticoagulation with Vitamin K antagonists (VKA). We
      investigate clinical outcomes in a consecutive population of VKA naive atrial
      fibrillation (AF) patients, who initiated VKA therapy in our clinic. We included
      consecutive VKA-naive patients with non valvular AF, initiated on VKA therapy in
      our anticoagulation outpatient clinic in 2009. During follow-up, adverse events
      [thrombotic/vascular events (stroke, acute coronary syndrome, acute heart failure
      and cardiac death), major bleeding and death], and VKA cessation were recorded.
      At the end of the follow-up, we determined time within therapeutic range (TTR),
      using a linear approximation (Rosendaal method). We studied 529 patients (49%
      male, median age 76), median follow-up 835 days (IQR 719-954). During this period
      114 patients stopped VKA treatment. 63 patients suffered a
      thrombotic/cardiovascular event (5.17%/year, 27 thrombotic/ischaemic strokes), 51
      major bleeding (4.19%/year) and 48 died (3.94%/year). Median TTR was 54% (34-57).
      On multivariate analysis (adjusted by CHA2DS2-VASc score), VKA cessation was
      associated with death [Hazard Ratio (HR) 3.43; p<0.001], stroke [4.21; p=0.001]
      and thrombotic/cardiovascular events [2.72; p<0.001]. Independent risk factors
      for major bleeding were age [1.08; p<0.001], previous stroke [1.85; p=0.049], and
      TTR [0.97; p=0.001], but not VKA cessation. In conclusion, in AF patients AF, VKA
      cessation is independently associated with mortality stroke and cardiovascular
      events. Specifically, VKA cessation independently increased the risk of stroke,
      even after adjusting for CHA2DS2-VASc score. TTR was an independent risk factor
      for major bleeding following initiation of VKA therapy.

PMID- 24096616
TI  - Echocardiographic changes and treatment goal rates after a 6-month combined
      treatment with amlodipine and losartan: a validation study in Andean countries
      (METAL study).
AB  - BACKGROUND: The extent to which treatment with amlodipine/losartan may help
      patients and their doctors from Andean countries to reach their treatment goals
      remains unknown. METHODS: We conducted a quasi-experimental, validation study in
      which patients with primary, uncomplicated hypertension received open-label,
      fixed combination therapy with amlodipine/losartan 5/50 mg or 5/100 mg according
      to their baseline blood pressure (BP). The primary outcome was echocardiographic
      reduction of left ventricular mass (LMV) after 6 months of treatment. Secondary
      outcomes were changes in BP, uricemia and albuminuria from baseline. We defined
      patients with adequately controlled hypertension as those with decreases in at
      least three out of these four variables. RESULTS: From 109 eligible patients with
      hypertension, 99 started the protocol (70 under the low-dose combination).
      Echocardiography indices had mutual correlation and contributed independently to
      the primary outcome (Cronbach's alpha index = 0.66). Intention-to-treat analysis
      showed that 60 patients [60.6%, 95% confidence interval (CI) 50.3-70.3] had
      reduced LVM. Echocardiographic changes were not associated with dose levels.
      Favorable changes in BP, uricemia and microabuminuria were seen in 77, 64 and 76
      patients respectively. After 6 months there were 64 (95% CI 54-74%) patients with
      adequately controlled hypertension. CONCLUSION: Every two of three patients of
      this sample of Andean countries reached adequate control after 6 months of
      combined antihypertensive treatment with amlodipine/losartan.

PMID- 24096617
TI  - Dipeptide repeat protein pathology in C9ORF72 mutation cases: clinico
      pathological correlations.
AB  - Hexanucleotide repeat expansion in C9ORF72 is the most common genetic cause of
      frontotemporal dementia and motor neuron disease. Recently, unconventional non
      ATG translation of the expanded hexanucleotide repeat, resulting in the
      production and aggregation of dipeptide repeat (DPR) proteins (poly-GA, -GR and
      GP), was identified as a potential pathomechanism of C9ORF72 mutations. Besides
      accumulation of DPR proteins, the second neuropathological hallmark lesion in
      C9ORF72 mutation cases is the accumulation of TDP-43. In this study, we
      characterized novel monoclonal antibodies against poly-GA and performed a
      detailed analysis of the neuroanatomical distribution of DPR and TDP-43 pathology
      in a cohort of 35 cases with the C9ORF72 mutation that included a broad spectrum
      of clinical phenotypes. We found the pattern of DPR pathology to be highly
      consistent among cases regardless of the phenotype with high DPR load in the
      cerebellum, all neocortical regions (frontal, motor cortex and occipital) and
      hippocampus, moderate pathology in subcortical areas and minimal pathology in
      lower motor neurons. No correlation between DPR pathology and the degree of
      neurodegeneration was observed, while a good association between TDP-43 pathology
      with clinical phenotype and degeneration in key anatomical regions was present.
      Our data confirm that the presence of DPR pathology is intimately related to
      C9ORF72 mutations. The observed dissociation between DPR inclusion body load and
      neurodegeneration might suggest inclusion body formation as a potentially
      protective response to cope with soluble toxic DPR species. Moreover, our data
      imply that alterations due to the C9ORF72 mutation resulting in TDP-43
      accumulation and dysmetabolism as secondary downstream effects likely play a
      central role in the neurodegenerative process in C9ORF72 pathogenesis.

PMID- 24096618
TI  - AKT1E17K mutations cluster with meningothelial and transitional meningiomas and
      can be detected by SFRP1 immunohistochemistry.
AB  - The activating E17K mutation in the AKT1 gene has been detected in several tumor
      entities. Currently several clinical studies with specific AKT1 inhibitors are
      under way. To determine whether AKT1 mutations are involved in human tumors of
      the nervous system, we examined a series of 1,437 tumors including 391 primary
      intracranial brain tumors and 1,046 tumors of the coverings of the central and
      peripheral nervous system. AKT1E17K mutations were exclusively seen in
      meningiomas and occurred in 65 of 958 of these tumors. A strong preponderance was
      seen in the variant of meningothelial meningioma WHO grade I of basal and spinal
      localization. In contrast, AKT1E17K mutations were rare in WHO grade II and
      absent in WHO grade III meningiomas. In order to more effectively detect this
      mutation, we tested for immunohistochemical markers associated with this
      alteration. We observed strong up-regulation of SFRP1 expression in all
      meningiomas with AKT1E17K mutation and in HEK293 cells after transfection with
      mutant AKT1E17K, but not in meningiomas and HEK293 cells lacking this mutation. 

PMID- 24096621
TI  - Use of survivorship care plans in the United States: associations with
      survivorship care.
AB  - BACKGROUND: Survivorship care plans (SCPs), including a treatment summary and
      follow-up plan, intend to promote coordination of posttreatment cancer care; yet,
      little is known about the provision of these documents by oncologists to primary
      care physicians (PCPs). This study compared self-reported oncologist provision
      and PCP receipt of treatment summaries and follow-up plans, characterized
      oncologists who reported consistent provision of these documents to PCPs, and
      examined associations between PCP receipt of these documents and survivorship
      care. METHODS: A nationally representative sample of medical oncologists (n =
      1130) and PCPs (n = 1020) were surveyed regarding follow-up care for breast and
      colon cancer survivors. All statistical tests were two-sided. Multivariable
      regression models identified factors associated with oncologist provision of
      treatment summaries and SCPs to PCPs (always/almost always vs less frequent).
      RESULTS: Nearly half of oncologists reported always/almost always providing
      treatment summaries, whereas 20.2% reported always/almost always providing SCPs
      (treatment summary + follow-up plan). Approximately one-third of PCPs indicated
      always/almost always receiving treatment summaries; 13.4% reported always/almost
      always receiving SCPs. Oncologists who reported training in late- and long-term
      effects of cancer and use of electronic medical records were more likely to
      report SCP provision (P < .05). PCP receipt of SCPs was associated with better
      PCP-reported care coordination, physician-physician communication, and confidence
      in survivorship care knowledge compared to receipt of neither treatment summaries
      nor SCPs (P < .05). CONCLUSIONS: Providing SCPs to PCPs may enhance survivorship
      care coordination, physician-physician communication, and PCP confidence.
      However, considerable progress will be necessary to achieve implementation of
      sharing SCPs among oncologists and PCPs.

PMID- 24096622
TI  - From Papanicolaou to papillomaviruses: evolving challenges in cervical cancer
      screening in the era of human papillomavirus vaccination.

PMID- 24096620
TI  - Screening for cervical cancer precursors with p16/Ki-67 dual-stained cytology:
      results of the PALMS study.
AB  - BACKGROUND: Pap cytology is known to be more specific but less sensitive than
      testing for human papillomavirus (HPV) for the detection of high-grade cervical
      intraepithelial neoplasia (CIN2+). We assessed whether p16/Ki-67 dual-stained
      cytology, a biomarker combination indicative of transforming HPV infections, can
      provide high sensitivity for CIN2+ in screening while maintaining high
      specificity. Results were compared with Pap cytology and HPV testing. METHODS: A
      total of 27,349 women 18 years or older attending routine cervical cancer
      screening were prospectively enrolled in five European countries. Pap cytology,
      p16/Ki-67 immunostaining, and HPV testing were performed on all women. Positive
      test results triggered colposcopy referral, except for women younger than 30
      years with only positive HPV test results. Presence of CIN2+ on adjudicated
      histology was used as the reference standard. Two-sided bias-corrected McNemar P
      values were determined. RESULTS: The p16/Ki-67 dual-stained cytology positivity
      rates were comparable with the prevalence of abnormal Pap cytology results and
      less than 50% of the positivity rates observed for HPV testing. In women of all
      ages, dual-stained cytology was more sensitive than Pap cytology (86.7% vs 68.5%;
      P < .001) for detecting CIN2+, with comparable specificity (95.2% vs 95.4%; P =
      .15). The relative performance of the tests was similar in both groups of women:
      younger than age 30 and 30 years or older. HPV testing in women 30 years or older
      was more sensitive than dual-stained cytology (93.3% vs 84.7%; P = .03) but less
      specific (93.0% vs 96.2%; P < .001). CONCLUSIONS: The p16/Ki-67 dual-stained
      cytology combines superior sensitivity and noninferior specificity over Pap
      cytology for detecting CIN2+. It suggests a potential role of dual-stained
      cytology in screening, especially in younger women where HPV testing has its
      limitations.

PMID- 24096623
TI  - Re: Height as an explanatory factor for sex differences in human cancer.

PMID- 24096619
TI  - The neuropathology of obesity: insights from human disease.
AB  - Obesity, a pathologic state defined by excess adipose tissue, is a significant
      public health problem as it affects a large proportion of individuals and is
      linked with increased risk for numerous chronic diseases. Obesity is the result
      of fundamental changes associated with modern society including overnutrition and
      sedentary lifestyles. Proper energy homeostasis is dependent on normal brain
      function as the master metabolic regulator, which integrates peripheral signals,
      modulates autonomic outflow and controls feeding behavior. Therefore, many human
      brain diseases are associated with obesity. This review explores the
      neuropathology of obesity by examining brain diseases which either cause or are
      influenced by obesity. First, several genetic and acquired brain diseases are
      discussed as a means to understand the central regulation of peripheral
      metabolism. These diseases range from monogenetic causes of obesity (leptin
      deficiency, MC4R deficiency, Bardet-Biedl syndrome and others) to complex
      neurodevelopmental disorders (Prader-Willi syndrome and Sim1 deficiency) and
      neurodegenerative conditions (frontotemporal dementia and Gourmand's syndrome)
      and serve to highlight the central regulatory mechanisms which have evolved to
      maintain energy homeostasis. Next, to examine the effect of obesity on the brain,
      chronic neuropathologic conditions (epilepsy, multiple sclerosis and Alzheimer's
      disease) are discussed as examples of obesity leading to maladaptive processes
      which exacerbate chronic disease. Thus, obesity is associated with multiple
      pathways including abnormal metabolism, altered hormonal signaling and increased
      inflammation which act in concert to promote downstream neuropathology. Finally,
      the effect of anti-obesity interventions is discussed in terms of brain structure
      and function. Together, understanding human diseases and anti-obesity
      interventions leads to insights into the bidirectional interaction between
      peripheral metabolism and central brain function, highlighting the need for
      continued clinicopathologic and mechanistic studies of the neuropathology of
      obesity. 

PMID- 24096624
TI  - Run-in phase III trial design with pharmacodynamics predictive biomarkers.
AB  - BACKGROUND: Developments in biotechnology have stimulated the use of predictive
      biomarkers to identify patients who are likely to benefit from a targeted
      therapy. Several randomized phase III designs have been introduced for
      development of a targeted therapy using a diagnostic test. Most such designs
      require biomarkers measured before treatment. In many cases, it has been very
      difficult to identify such biomarkers. Promising candidate biomarkers can
      sometimes be effectively measured after a short run-in period on the new
      treatment. METHODS: We introduce a new design for phase III trials with a
      candidate predictive pharmacodynamic biomarker measured after a short run-in
      period. Depending on the therapy and the biomarker performance, the trial would
      either randomize all patients but perform a separate analysis on the biomarker
      positive patients or only randomize marker-positive patients after the run-in
      period. We evaluate the proposed design compared with the conventional phase III
      design and discuss how to design a run-in trial based on phase II studies.
      RESULTS: The proposed design achieves a major sample size reduction compared with
      the conventional randomized phase III design in many cases when the biomarker has
      good sensitivity (>=0.7) and specificity (>=0.7). This requires that the
      biomarker be measured accurately and be indicative of drug activity. However, the
      proposed design loses some of its advantage when the proportion of potential
      responders is large (>50%) or the effect on survival from run-in period is
      substantial. CONCLUSIONS: Incorporating a pharmacodynamic biomarker requires
      careful consideration but can expand the capacity of clinical trials to
      personalize treatment decisions and enhance therapeutics development.

PMID- 24096625
TI  - Built environment and physical activity for transportation in adults from
      Curitiba, Brazil.
AB  - The goal of this study was to assess the association between features of the
      built environment and levels of walking and cycling as forms of transportation in
      the city of Curitiba, Brazil. Data collection was conducted through a telephone
      survey in 2008. The International Physical Activity Questionnaire was used to
      identify walking or cycling as forms of transportation. The built environment
      characteristics were obtained through the Geographic Information System for 1,206
      adults. Density indicators were computed, considering a radius of 500 m around
      each individual's household. For the accessibility measures, the shortest
      distance to selected built environment features (e.g., bus stop, bike path) was
      used. The association between characteristics of the environment and the practice
      of walking or cycling was assessed through logistic regressions. After
      considering individual characteristics, higher-income areas (OR = 0.56, 95 % CI =
      0.41-0.76), higher density of Bus Rapid Transit stations (OR = 1.50, 95 % CI =
      1.22-1.84), and the proportion of residential (OR = 1.25, 95 % CI = 1.02-1.53)
      and commercial (OR = 1.47, 95 % CI = 1.13-1.91) areas were associated with any
      walking prevalence (>= 10 min/week). Higher access to bike paths (OR = 0.80, 95 %
      CI = 0.64-1.00) was inversely associated with walking at recommended levels (>=
      150 min/week). Higher-income areas (OR = 0.26, 95 % CI = 0.08-0.81), greater
      number of traffic lights (OR = 0.27, 95 % CI = 0.09-0.88), and higher land use
      mix (OR = 0.52, 95 % CI = 0.31-0.88) were inversely associated with cycling. The
      neighborhood built environment may affect active commuting among adults living in
      urban centers in middle-income countries.

PMID- 24096626
TI  - Mitochondrial cumulative damage induced by mitoxantrone: late onset cardiac
      energetic impairment.
AB  - Mitoxantrone (MTX) is a chemotherapeutic agent, which presents late irreversible
      cardiotoxicity. This work aims to highlight the mechanisms involved in the MTX
      induced cardiotoxicity, namely the effects toward mitochondria using in vivo and
      in vitro studies. Male Wistar rats were treated with 3 cycles of 2.5 mg/kg MTX at
      day 0, 10, and 20. One treated group was euthanized on day 22 (MTX22) to evaluate
      the early MTX cardiac toxic effects, while the other was euthanized on day 48
      (MTX48), to allow the evaluation of MTX late cardiac effects. Cardiac
      mitochondria isolated from 4 adult untreated rats were also used to evaluate in
      vitro the MTX (10 nM, 100 nM, and 1 MUM) direct effects upon mitochondria
      functionality. Two rats of MTX48 died on day 35, and MTX treatment caused a
      reduction in relative body weight gain in both treated groups with no significant
      changes in water and food intake. Decreased levels of plasma total creatine
      kinase and CK-MB were detected in the MTX22 group, and increased plasma levels of
      lactate were seen in MTX48. Increased cardiac relative mass and microscopic
      changes were evident in both treated groups. Considering mitochondrial effects,
      for the first time, it was evidenced that MTX induced an increase in the complex
      IV and complex V activities in MTX22 group, while a decrease in the complex V
      activity was accompanied by the reduction in ATP content in the MTX48 rats. No
      alterations in mitochondria transmembrane potential were found in isolated
      mitochondria from MTX48 rats or in isolated mitochondria directly incubated with
      MTX. This study highlights the relevance of the cumulative MTX-induced in vivo
      mitochondriopathy to the MTX cardiotoxicity. 

PMID- 24096627
TI  - Functional characterization of protein 4.1 homolog in amphioxus: defining a
      cryptic spectrin-actin-binding site.
AB  - Vertebrate 4.1 proteins have a spectrin-actin-binding (SAB) domain, which is
      lacking in all the invertebrate 4.1 proteins indentified so far, and it was
      therefore proposed that the SAB domain emerged with the advent of vertebrates
      during evolution. Here we demonstrated for the first time that amphioxus (an
      invertebrate chordate) protein 4.1, though lacking a recognizable SAB, was able
      to bind both spectrin and actin, with a binding capacity comparable to that of
      human protein 4.1. Detailed structure-activity analyses revealed that the unique
      domain U2/3 was a newly identified SAB-like domain capable of interacting with
      spectrin and actin, suggesting the presence of a "cryptic" SAB domain in
      amphioxus 4.1 protein. We also showed that amphioxus 4.1 protein gene was the
      common ancestor of vertebrate 4.1 protein genes, from which 4.1R, 4.1N, 4.1G, and
      4.1B genes originated. This work will encourage further study on the structure
      activity of invertebrate 4.1 protein and its interacting proteins. 

PMID- 24096628
TI  - Anisotropic breakdown of Fermi liquid quasiparticle excitations in overdoped La2
      xSrxCuO4.
AB  - High-temperature superconductivity emerges from an un-conventional metallic
      state. This has stimulated strong efforts to understand exactly how Fermi liquids
      breakdown and evolve into an un-conventional metal. A fundamental question is how
      Fermi liquid quasiparticle excitations break down in momentum space. Here we
      show, using angle-resolved photoemission spectroscopy, that the Fermi liquid
      quasiparticle excitations of the overdoped superconducting cuprate
      La1.77Sr0.23CuO4 is highly anisotropic in momentum space. The quasiparticle
      scattering and residue behave differently along the Fermi surface and hence the
      Kadowaki-Wood's relation is not obeyed. This kind of Fermi liquid breakdown may
      apply to a wide range of strongly correlated metal systems where spin
      fluctuations are present. 

PMID- 24096629
TI  - Congenital linear streaks on the face and neck and microphthalmia in an infant
      girl.

PMID- 24096630
TI  - HIV-1 infection induces strong production of IP-10 through TLR7/9-dependent
      pathways.
AB  - OBJECTIVE: To study the cytokine/chemokine profiles in response to HIV-1 viremia,
      and elucidate the pathways leading to HIV-1-induced inflammation. DESIGN/METHODS:
      Plasma levels of 19 cytokines in individuals with early HIV-1 infection and
      individuals undergoing treatment interruptions were evaluated via multiplex
      assay. To investigate the cellular sources of relevant cytokines, sorted cells
      from HIV-1 infected individuals were assessed for mRNA expression. Relevant
      signaling pathways were assessed by comparing cytokine production patterns of
      peripheral blood mononuclear cells stimulated with intact HIV-1 or specific Toll
      like receptor (TLR) stimulants with and without a TLR7/9 antagonist. RESULTS: IP
      10 plasma concentration was most significantly associated with HIV-1 viral load
      and was the most significant contributor in a multivariate model. IP-10 mRNA was
      highly expressed in monocytes and mDCs and these cells were the dominant
      producers after in-vitro stimulation with TLR7/8 ligands (CL097 and
      ssRNAGag1166), AT-2 HIV-1, and HIV-1NL43 virus. Partial least square discriminant
      analysis of culture supernatants revealed distinct cytokine/chemokine secretion
      profiles associated with intact viruses compared with TLR7/8 ligands alone, with
      IP-10 production linked to the former. A TLR7/9 antagonist blocked IP-10
      production following whole virus stimulation, suggesting the involvement of
      TLR7/9 in the recognition of HIV-1 by these cells. CONCLUSION: Monocytes and mDCs
      produce significant amounts of IP-10 in response to HIV-1 viremia and after in
      vitro stimulation with HIV-1. Stimulation with HIV-1-derived TLR7/8-ligands
      versus HIV-1 resulted in distinct cytokine/chemokine profiles, indicating
      additional pathways other than TLR7/8 that lead to the activation of innate
      immune cells by HIV-1.

PMID- 24096631
TI  - Paradoxical tuberculosis-associated immune reconstitution inflammatory syndrome
      after early initiation of antiretroviral therapy in a randomized clinical trial.
AB  - OBJECTIVE: To analyze cases of paradoxical tuberculosis-associated immune
      reconstitution inflammatory syndrome (TB-IRIS) in the CAMbodian Early versus Late
      Introduction of Antiretrovirals (CAMELIA) randomized trial designed to compare
      early (2 weeks) versus late (8 weeks) antiretroviral therapy (ART) initiation
      after tuberculosis treatment onset in Cambodia (NCT00226434). METHODS: ART-naive
      adults with CD4 cell count of 200 cells/MUl or less, newly diagnosed
      tuberculosis, and at least one follow-up visit after ART initiation were included
      in this analysis. Each case of suspected TB-IRIS was systematically validated by
      two physicians not involved in patients' management. Factors associated with
      occurrence of TB-IRIS were identified using the Cox proportional hazard model.
      RESULTS: Among 597 patients, 26% experienced TB-IRIS with an incidence rate of
      37.9 cases per 100 person-years [95% confidence interval (CI) 32.4-44.4]. Main
      clinical manifestations included new or worsening lymphadenopathy (77.4%) and
      fever (68.4%). Chest radiograph revealed new or worsening abnormalities in 53.4%.
      Symptoms resolved in 95.5% of patients. Six deaths were directly related to TB
      IRIS. Initiating ART early increased the risk of TB-IRIS by 2.61 (95% CI 1.84
      3.70). Extrapulmonary or disseminated tuberculosis, CD4 cell count of 100
      cells/MUl or less, and HIV RNA concentration more than 6 log10 copies/ml were
      also significantly associated with higher risk of TB-IRIS. CONCLUSION: Shortening
      the delay between tuberculosis treatment onset and ART initiation to 2 weeks was
      associated with an increased risk of developing TB-IRIS. However, TB-IRIS was
      generally easily manageable. Given the marked reported survival advantage of
      early ART initiation after tuberculosis treatment onset, these data indicate that
      fear of TB-IRIS should not be an impediment to early ART in adults with advanced
      immunodeficiency in resource-limited, high burden settings.

PMID- 24096632
TI  - Glucose tolerance in HIV-1 treated patients who switched from boosted-protease
      inhibitors to etravirine.

PMID- 24096633
TI  - The nomenclature of a new HIV circulating recombinant form should be cautious.

PMID- 24096634
TI  - Clinician-trialist rounds: 19. Faux pas or fraud? Identifying centers that have
      fabricated their data in your multi-center trial.

PMID- 24096635
TI  - Network meta-analysis of randomized clinical trials: reporting the proper
      summaries.
AB  - BACKGROUND: In the absence of sufficient data directly comparing multiple
      treatments, indirect comparisons using network meta-analyses (NMAs) can provide
      useful information. Under current contrast-based (CB) methods for binary
      outcomes, the patient-centered measures including the treatment-specific event
      rates and risk differences (RDs) are not provided, which may create some
      unnecessary obstacles for patients to comprehensively trade-off efficacy and
      safety measures. PURPOSE: We aim to develop NMA to accurately estimate the
      treatment-specific event rates. METHODS: A Bayesian hierarchical model is
      developed to illustrate how treatment-specific event rates, RDs, and risk ratios
      (RRs) can be estimated. We first compare our approach to alternative methods
      using two hypothetical NMAs assuming a fixed RR or RD, and then use two published
      NMAs to illustrate the improved reporting. RESULTS: In the hypothetical NMAs, our
      approach outperforms current CB NMA methods in terms of bias. In the two
      published NMAs, noticeable differences are observed in the magnitude of relative
      treatment effects and several pairwise statistical significance tests from
      previous report. LIMITATIONS: First, to facilitate the estimation, each study is
      assumed to hypothetically compare all treatments, with unstudied arms being
      missing at random. It is plausible that investigators may have selected treatment
      arms on purpose based on the results of previous trials, which may lead to
      'nonignorable missingness' and potentially bias our estimates. Second, we have
      not considered methods to identify and account for potential inconsistency
      between direct and indirect comparisons. CONCLUSIONS: The proposed NMA method can
      accurately estimate treatment-specific event rates, RDs, and RRs and is
      recommended.

PMID- 24096636
TI  - Beyond intention to treat: what is the right question?
AB  - BACKGROUND: Most methodologists recommend intention-to-treat (ITT) analysis in
      order to minimize bias. Although ITT analysis provides an unbiased estimate for
      the effect of treatment assignment on the outcome, the estimate is biased for the
      actual effect of receiving treatment (active treatment) compared to some
      comparison group (control). Other common analyses include measuring effects in
      (1) participants who follow their assigned treatment (Per Protocol), (2)
      participants according to treatment received (As Treated), and (3) those who
      would comply with recommended treatment (Complier Average Causal Effect (CACE) as
      estimated by Principal Stratification or Instrumental Variable Analyses). As each
      of these analyses compares different study subpopulations, they address different
      research questions. PURPOSE: For each type of analysis, we review and explain (1)
      the terminology being used, (2) the main underlying concepts, (3) the questions
      that are answered and whether the method provides valid causal estimates, and (4)
      the situations when the analysis should be conducted. METHODS: We first review
      the major concepts in relation to four nuances of the clinical question, 'Does
      treatment improve health?' After reviewing these concepts, we compare the results
      of the different analyses using data from two published randomized controlled
      trials (RCTs). Each analysis has particular underlying assumptions and all
      require dichotomizing adherence into Yes or No. We apply sensitivity analyses so
      that intermediate adherence is considered (1) as adherence and (2) as non
      adherence. RESULTS: The ITT approach provides an unbiased estimate for how active
      treatment will improve (1) health in the population if a policy or program is
      enacted or (2) health of patients if a clinician changes treatment practice. The
      CACE approach generally provides an unbiased estimate of the effect of active
      treatment on health of patients who would follow the clinician's advice to take
      active treatment. Unfortunately, there is no current analysis for clinicians and
      patients who want to know whether active treatment will improve the patient's
      health if taken, which is different from the effect in patients who would follow
      the clinician's advice to take active treatment. Sensitivity analysis for the
      CACE using two published data sets suggests that the underlying assumptions
      appeared to be violated. LIMITATIONS: There are several methods within each
      analytical approach we describe. Our analyses are based on a subset of these
      approaches. CONCLUSIONS: Although adherence-based analyses may provide meaningful
      information, the analytical method should match the clinical question, and
      investigators should clearly outline why they believe assumptions hold and should
      provide empirical tests of the assumptions where possible.

PMID- 24096638
TI  - Health-related internet use by lupus patients in southern Spain.
AB  - Internet has become a widely used tool by patients seeking information on
      different diseases. The information regarding lupus patients' Internet use is
      scarce. This study aims to explore the attitudes and practices of lupus patients
      in southern Spain, regarding Internet use to find health-related information. A
      survey was carried out including 150 patients from six Andalusian Hospitals. To
      search for information, 67.3 % of the patients used Internet. The proportion of
      female Internet users was higher (69.3 vs 46.2 %), particularly those belonging
      to a patients' association (81.8 vs 32.7 %), and are regular users of Internet
      (80.2 vs 44.4 %); 37.5 % thought the information found in the Internet was of
      little use or not useful at all, and 58 % of the respondents stated that the
      information found caused them concern while for 27 %, it was a relief. Most
      patients preferred the information given by their physicians (63.6 %); 33.9 %
      considered that the information from both sources was complementary, and 2.5 %
      preferred the information obtained from the Internet. A percentage of 85.3 of the
      patients would like their physicians to provide them with information on high
      quality sites regarding their illness. Lupus patients make frequent use of the
      Internet to look for information on their disease. Considering this, and because
      better-informed patients follow more precisely the indications given by the
      physician, medical staff should collaborate in the development of high-quality
      sites for the patient to have additional sources of information. 

PMID- 24096639
TI  - Central nervous system angiitis: a series of 31 patients.
AB  - Central nervous system (CNS) angiitis is a rare inflammatory disorder. To date,
      clinical data are lacking and treatment remains a matter of debate. The aim of
      this study is to analyse the main characteristics, response to therapy and
      outcome of 32 patients with CNS angiitis. Single-centre retrospective study in a
      tertiary centre was made. Diagnosis of CNS angiitis was made by cerebral
      angiography and/or magnetic resonance angiography and/or CNS biopsy. The main
      features and outcomes of primary and secondary CNS angiitis were compared and
      predictive factors of a favourable outcome were searched. Thirty-one patients
      (median age 45 Q1-Q3 37-54) sex ratio F/M 2.1) were included. Main clinical
      features were hemiparesis (35.5 %) and headache (29 %). The median CSF protein
      level was 0.64(0.52-0.81) g/L and was superior to 1 g/L in six cases. CNS
      magnetic resonance (MR) imaging findings were most frequently ischemic (96.8 %),
      bilateral (83.9 %), multiple (87.1 %) and supratentorial (96.8 %). The MR
      angiography was abnormal in all cases. Among the 31 patients in the study, 19
      (61.3 %) were diagnosed with primary CNS angiitis. Systemic lupus erythematosus
      (n = 6) and vasculitis (n = 4) were the most frequent aetiologies of secondary
      CNS angiitis. No difference was evidenced between primary and secondary CNS
      angiitis. Steroids were administered in 79.2 % of treated patients and combined
      with immunosuppressants in 79.2 % of cases. Eight cases of CNS angiitis relapse
      were noted. CNS angiitis remains a severe illness. Treatment often associated
      steroids and immunosuppressants, and diagnosis delay is significantly associated
      with a poorer prognosis. 

PMID- 24096640
TI  - Predictors of exclusive breastfeeding at least 8 weeks among Asian and Native
      Hawaiian or other Pacific Islander race subgroups in Hawaii, 2004-2008.
AB  - Breastfeeding is nurturing, cost-effective, and beneficial for the health of
      mother and child. Babies receiving formula are sick more often and are at higher
      risk for childhood obesity, diabetes, asthma, and other conditions compared with
      breastfed children. National and international organizations recommend exclusive
      breastfeeding for 6 months. Exclusive breastfeeding in Asian and Native Hawaiian
      or Other Pacific Islander (NHOPI) subgroups is not well characterized. Data from
      the 2004-2008 Hawaii Pregnancy Risk Assessment Monitoring System, a population
      based surveillance system on maternal behaviors and experiences before, during,
      and after pregnancy, were analyzed for 8,508 mothers with a recent live birth. We
      examined exclusive breastfeeding status for at least 8 weeks. We calculated
      prevalence risk ratios across maternal race groups accounting for maternal and
      socio-demographic characteristics. The overall estimate of exclusive
      breastfeeding for at least 8 weeks was 36.3%. After adjusting for maternal age,
      pre-pregnancy weight, cesarean delivery, return to work/school, and self-reported
      postpartum depressive symptoms, the racial differences in prevalence ratios for
      exclusive breastfeeding for each ethnic group compared to Whites were: Samoan
      (aPR = 0.54; 95% CI 0.43-0.69), Filipino (aPR = 0.58; 95% CI 0.53-0.63), Japanese
      (aPR = 0.58; 95% CI 0.52-0.65), Chinese (aPR = 0.64; 95% CI 0.58-0.70), Native
      Hawaiian (aPR = 0.67; 95% CI 0.61-0.72), Korean (aPR = 0.72; 95% CI 0.64-0.82),
      and Black (aPR = 0.79; 95% CI 0.65-0.96) compared to white mothers. Providers and
      community groups should be aware that just over one-third of mothers breastfeed
      exclusively at least 8 weeks with lower rates among Asian, NHOPI, and Black
      mothers. Culturally appropriate efforts to promote exclusive breastfeeding are
      recommended particularly among Asian subgroups that have high breastfeeding
      initiation rates that do not translate into high exclusivity rates.

PMID- 24096641
TI  - Effects of non-dipper blood pressure pattern on left ventricular rotational
      mechanics in hypertensive patients with type 2 diabetes mellitus: a speckle
      tracking study.
AB  - We aimed to evaluate the effects of non-dipper BP pattern on left ventricular
      (LV) rotational mechanics in hypertensive patients with type 2 diabetes mellitus
      (T2DM) with the utility of two-dimensional speckle tracking echocardiography (2D
      STE). Eighty-six hypertensive patients with T2DM were enrolled. All patients
      underwent 2D-echocardiography and 24-h-ambulatory blood pressure monitoring.
      Fifty-nine (59.3%) patients had non-dipper BP pattern and all subjects had normal
      LV function. Patients with non-dipper BP pattern had decreased systolic tissue
      velocity (p: 0.006), increased peak systolic apical rotation and rotation rate
      (p: 0.008 and p: 0.014, respectively), and peak LV twist and twist rate (p: 0.005
      and p: 0.012, respectively). Analysis of LV diastolic parameters showed that,
      early diastolic tissue velocity (Em) was decreased and E/Em ratio and LV mass
      (LVM) index were increased in non-dipper group while the time to LV untwisting
      rate was delayed. In multivariate analysis, peak LV twist (beta = 0.459, p: <
      0.001) and twist rate (beta = 0.388, p: 0.001) were independently associated with
      the difference between mean arterial pressure (MAP)-asleep and MAP-awake. In
      correlation analysis adjusted for age, sex and LVM index, the time to LV
      untwisting rate was positively correlated with the difference between MAP-asleep
      and MAP-awake (r: 0.290 vs. p: 0.008) and E/Em ratio (r: 0.280 vs. p: 0.010). LV
      rotational mechanics are impaired in T2DM non-dipper hypertensive patients,
      indicating LV systolic and diastolic dysfunction. 2D-STE may permit better
      understanding of the underlying pathophysiology and development of preventive
      strategies.

PMID- 24096643
TI  - Hydrogen sulfide and translational medicine.
AB  - Hydrogen sulfide (H2S) along with carbon monoxide and nitric oxide is an
      important signaling molecule that has undergone large numbers of fundamental
      investigations. H2S is involved in various physiological activities associated
      with the regulation of homeostasis, vascular contractility, pro- and anti
      inflammatory activities, as well as pro- and anti-apoptotic activities etc.
      However, the actions of H2S are influenced by its concentration, reaction time,
      and cell/disease types. Therefore, H2S is a signaling molecule without definite
      effect. The use of existing H2S donors is limited because of the instant release
      and short lifetime of H2S. Thus, translational medicine involving the sustained
      and controlled release of H2S is of great value for both scientific and clinical
      uses. H2S donation can be manipulated by different ways, including where H2S is
      given, how H2S is donated, or the specific structures of H2S-releasing drugs and
      H2S donor molecules. This review briefly summarizes recent progress in research
      on the physiological and pathological functions of H2S and H2S-releasing drugs,
      and suggests hope for future investigations. 

PMID- 24096644
TI  - Transdermal fentanyl for cancer pain.
AB  - BACKGROUND: Opioid drugs have been used for many years to relieve pain.
      Transdermal fentanyl offers one option for delivering and maintaining pain relief
      in patients with moderate or severe cancer pain. OBJECTIVES: To determine the
      analgesic efficacy of transdermal fentanyl for relief of cancer pain, and to
      assess the adverse events associated with the use of transdermal fentanyl for
      relief of cancer pain. SEARCH METHODS: The following databases were searched:
      Cochrane Central Register of Controlled Trials (CENTRAL) (The Cochrane Library
      2013, Issue 4 of 12); MEDLINE (1966 to May 2013); EMBASE (1974 to May 2013;
      CANCERLIT (PubMED) (November 2012); and ClinicalTrials.gov (May 2013). SELECTION
      CRITERIA: Published randomised controlled trials (RCTs) using placebo or active
      comparators reporting on the analgesic effect of transdermal fentanyl in adults
      and children with cancer pain. Studies with fewer than 10 participants were
      excluded. DATA COLLECTION AND ANALYSIS: Data were extracted independently by two
      review authors. We extracted any available data on the number or proportion of
      patients with 'no worse than mild pain' or treatment success (very satisfied, or
      very good or excellent on patient global impression scales), together with
      information about adverse events and withdrawals. MAIN RESULTS: We identified
      nine studies meeting the inclusion criteria, including a Turkish study that is
      awaiting formal translation. There were 1244 participants randomised in
      classically designed RCTs, of whom 1197 had evaluable data, and 138 patients
      enrolled in an enriched enrolment, randomised withdrawal (EERW) trial. Overall,
      600 participants were treated with transdermal fentanyl patches, 382 with various
      formulations of morphine, 36 with methadone, and 221 with paracetamol plus
      codeine. There were major sources of potential bias, including lack of blinding,
      small size, high levels of attrition, and inconsistent reporting.We could not
      compare data in a meaningful analysis regarding adverse events such as nausea,
      abdominal pain, gastrointestinal bleeding, and confusion. These events may have
      been attributable to the underlying disease process.There were insufficient
      comparable data for meta-analysis to be undertaken or to produce numbers needed
      to treat (NNT) for the analgesic effect. In seven studies with 461 participants
      reporting pain intensity results after about two weeks, the mean or median pain
      scores were on the borderline of mild and moderate pain. Most participants would
      have had no worse than mild pain on treatment. Another reported that 77% of
      participants using transdermal fentanyl had an undefined successful outcome.
      Fewer participants experienced constipation with transdermal fentanyl (28%) than
      with oral morphine (46%), giving a risk ratio of 0.61 (95% CI 0.47 to 0.78); the
      NNT to prevent constipation was 5.5 (95% CI 3.8 to 10). AUTHORS' CONCLUSIONS: The
      randomised trial literature for effectiveness of transdermal fentanyl is limited,
      but it is an important medicine. Most studies recruited fewer than 100
      participants and did not provide data appropriate for meta-analysis. Only a few
      reported how many patients had good pain relief but, where data were reported, a
      majority had no worse than mild pain within a reasonably short time period. The
      evidence pointed to a useful and significant reduction in complaints about
      constipation for transdermal fentanyl compared with oral morphine.

PMID- 24096642
TI  - Characteristics of human infection with avian influenza viruses and development
      of new antiviral agents.
AB  - Since 1997, several epizootic avian influenza viruses (AIVs) have been
      transmitted to humans, causing diseases and even deaths. The recent emergence of
      severe human infections with AIV (H7N9) in China has raised concerns about
      efficient interpersonal viral transmission, polygenic traits in viral
      pathogenicity and the management of newly emerging strains. The symptoms
      associated with viral infection are different in various AI strains: H5N1 and
      newly emerged H7N9 induce severe pneumonia and related complications in patients,
      while some H7 and H9 subtypes cause only conjunctivitis or mild respiratory
      symptoms. The virulence and tissue tropism of viruses as well as the host
      responses contribute to the pathogenesis of human AIV infection. Several
      preventive and therapeutic approaches have been proposed to combat AIV infection,
      including antiviral drugs such as M2 inhibitors, neuraminidase inhibitors, RNA
      polymerase inhibitors, attachment inhibitors and signal-transduction inhibitors
      etc. In this article, we summarize the recent progress in researches on the
      epidemiology, clinical features, pathogenicity determinants, and available or
      potential antivirals of AIV.

PMID- 24096645
TI  - Exploring mechanisms of human disease through structurally resolved protein
      interactome networks.
AB  - The study of the molecular basis of human disease has gained increasing attention
      over the past decade. With significant improvements in sequencing efficiency and
      throughput, a wealth of genotypic data has become available. However the
      translation of this information into concrete advances in diagnostic and clinical
      setups has proved far more challenging. Two major reasons for this are the lack
      of functional annotation for genomic variants and the complex nature of genotype
      to-phenotype relationships. One fundamental approach to bypass these issues is to
      examine the effects of genetic variation at the level of proteins as they are
      directly involved in carrying out biological functions. Within the cell, proteins
      function by interacting with other proteins as a part of an underlying
      interactome network. This network can be determined using interactome mapping - a
      combination of high-throughput experimental toolkits and curation from small
      scale studies. Integrating structural information from co-crystals with the
      network allows generation of a structurally resolved network. Within the context
      of this network, the structural principles of disease mutations can be examined
      and used to generate reliable mechanistic hypotheses regarding disease
      pathogenesis. 

PMID- 24096646
TI  - Diterpene para-hydroquinone compounds derived from cryptoquinone inhibit
      adipocyte differentiation of mouse 3T3-L1 cells and activate the Nrf2/ARE
      pathway.
AB  - Cryptoquinone, an abietane-type diterpene para-quinone from the bark of
      Cryptomeria japonica has antifungal and cytotoxic activities, but its biological
      actions are largely unknown. In this study, we found that para-hydroquinone
      derivatives inhibited adipocyte differentiation. The actions might have been
      mediated, at least in part, by activation of the antioxidant-response element
      induction of phase 2 enzymes and increases in total glutathione. 

PMID- 24096647
TI  - Anti-diabetic potential of the essential oil of Pinus koraiensis leaves toward
      streptozotocin-treated mice and HIT-T15 pancreatic beta cells.
AB  - The metabolic syndrome creates risk factors for coronary heart disease, diabetes,
      fatty liver, obesity and several cancers. Our group has already reported that the
      essential oil from leaves of Pinus koraiensis SIEB (EOPK) exerted
      antihyperlipidemic effects by upregulating the low-density lipoprotein receptor
      and inhibiting acyl-coenzyme A, cholesterol acyltransferases. We evaluated in the
      current study the anti-diabetic effects of EOPK on mice with streptozotocin (STZ)
      induced type I diabetes and on HIT-T15 pancreatic beta cells. EOPK significantly
      protected HIT-T15 cells from STZ-induced cytotoxicity and reduced the blood
      glucose level in STZ-induced diabetic mice when compared with the untreated
      control. EOPK consistently and significantly suppressed the alpha-amylase
      activity in a dose-dependent manner and enhanced the expression of insulin at the
      mRNA level in STZ-treated HIT-T15 cells, while the expression of insulin was
      attenuated. EOPK also significantly abrogated the population of reactive oxygen
      species when compared to the untreated control in STZ-treated HIT-T15 cells.
      Furthermore, EOPK significantly reduce nitric oxide production, suppressed the
      phosphorylation of endothelial nitric oxide (NO) synthase and suppressed the
      production of vascular endothelial growth factor (VEGF) in STZ-treated HIT-T15
      cells, implying its potential application to diabetic retinopathy. Overall, our
      findings suggest that EOPK had hypoglycemic potential by inhibiting reactive
      oxygene species (ROS), endothelial NO synthase (eNOS) and VEGF in STZ-treated
      mice and HIT-T15 pancreatic beta cells as a potent anti-diabetic agent. 

PMID- 24096648
TI  - Inhibited apoptosis of C(2)C(1)2 myoblasts by a Eupatorium chinense var.
      simplicifolium root extract.
AB  - We investigated the effects of a Eupatorium chinense var. simplicifolium (EUC)
      root extract on muscle disorders and explored the underlying mechanism for
      oxidative stress-induced C(2)C(12) myoblast damage. An EUC pre-treatment reduced
      the decreased cell viability after an H2O2 treatment. The heat shock protein
      (HSP) 70 level increased, and the phosphorylation of Jun amino-terminal kinases
      (JNKs) decreased in the EUC-pre-treated C(2)C(12) myoblasts. The results of the
      present study demonstrate the potential benefit of a herbal medicine in treating
      oxidative stress-related muscle disorders.

PMID- 24096649
TI  - The relationship between the fracture properties and the tissue structure of
      roasted sesame seeds.
AB  - Using seven varieties of roasted sesame seeds, we examined the relationship
      between the fracture properties and the internal structure of roasted seeds.
      Analysis of fracture properties revealed significant differences across the
      samples in terms of fracture force and fracture strain at the biggest fracture
      point, and in the number of small fractures (p<0.05). Analysis of the cross
      sectional structure revealed significant differences across the samples in the
      size of the void at the center of the sesame seed and in the overall thickness of
      the seed (p<0.05). Strong negative correlations were found for the center-void-to
      seed thickness ratio against fracture force and fracture strain at the biggest
      fracture point. Moreover, fracture properties and cross-sectional structure were
      strongly correlated with sensory evaluations of crispness. Hence we concluded
      that the presence of a void in the central area of a seed decreases the necessary
      fracture force, resulting in a crispy texture. 

PMID- 24096650
TI  - Simple method for refining arabinan polysaccharides by alcohol extraction of the
      prune, Prunus domestica L.
AB  - L-Arabinose is a useful sugar in the food industry. We demonstrate here simple
      methods for refining arabinan polysaccharides by alcohol extraction from prune,
      Prunus domestica L., as a source of L-arabinose. Alcohol-soluble polysaccharides
      were purified from a solution of prune extracted by 80% ethanol. After
      fractionating the polysaccharides by ion-exchange chromatography, arabinans were
      identified as mainly constituted by (1->5)-linked arabinofuranosyl units.

PMID- 24096651
TI  - Overproduction of hyperthermostable beta-1,4-endoglucanase from the archaeon
      Pyrococcus horikoshii by tobacco chloroplast engineering.
AB  - One of the most cost-effective methods of producing industrial enzymes is by the
      use of transgenic plants. We demonstrated successful high-level expression of a
      hyperthermostable archaeal beta-1,4-endoglucanase in mature tobacco leaves by
      transformation of chloroplasts by homologous recombination. The active
      recombinant enzyme was readily recovered not only from fresh but also from dried
      leaves. 

PMID- 24096652
TI  - Modulation of oxidative stress by proanthocyanidin in H2O2-exposed human diploid
      fibroblast cells.
AB  - Proanthocyanidin (a persimmon-peel extract) is known to have potent antioxidative
      effects, but its protective action specifically against cellular damage has not
      been fully explored. In this work, we investigated the protective property of
      proanthocyanidin against cellular oxidative stress with an experimental model,
      H2O2-exposed human diploid fibroblasts (HDFs). To investigate the proposed
      underlying beneficial actions of proanthocyanidin as to cellular injury induced
      by H2O2, several major biochemical parameters were determined, including
      estimation of total reactive species (RS) generation, antioxidant enzyme
      activities, reduced glutathione (GSH)/oxidized glulathione (GSSG) ratio, and
      mitochondrial membrane potential. The results indicate that proanthocyanidin
      reduced total RS generation while enhancing the activities of catalase and
      glutathione reductase and the GSH/GSSG ratio. Additionally, proanthocyanidin was
      found to protect against mitochondrial membrane damage in HDFs treated H2O2.
      Based on these results, we conclude that proanthocyanidin has strong protective
      effects against cellular damage to several key cellular functions by suppressing
      oxidative stress in H2O2-treated HDFs. 

PMID- 24096653
TI  - Alleviation of weight-gain in mice by an ethanolic extract from Rubus coreanus
      under conditions of a high-fat diet and exercise.
AB  - The administration of an ethanolic extract (RCE) from Rubus coreanus
      significantly reduced the body weight and epididymal fat tissue of mice under
      conditions of a high-fat diet (HFD) and exercise. The mice also displayed
      enhanced muscular carnitine palmitoyltransferase 1 (CPT1) expression and
      increased superoxide dismutase and glutathione levels. These results suggest that
      RCE exerted an anti-obesity effect by up-regulating CPT1 and elevating the level
      of antioxidants. 

PMID- 24096654
TI  - Calcitonin gene-related peptide upregulates serum amyloid A synthesis through
      activation of interleukin-6.
AB  - We found that calcitonin gene-related peptide (CGRP) enhanced the expression of
      levels of serum amyloid A (SAA) and interleukin-6 (IL-6) in HepG2. In addition,
      CGRP-induced SAA1/2 mRNA expression was blocked by an anti-IL-6 neutralizing
      antibody in HepG2. These results suggest that CGRP promotes SAA synthesis through
      activation of IL-6 in human hepatocytes. 

PMID- 24096655
TI  - Antioxidant activity potential of Virginia (flue-cured) tobacco flower
      polysaccharide fractions obtained by ultrasound-assisted extraction.
AB  - Ultrasound-assisted extraction was employed to extract polysaccharide from
      Virginia (flue-cured) tobacco flowers. The orthogonal matrix method (L9(3)(4))
      was used to determine the optimal extraction conditions as to ultrasound power,
      extraction time, ratio of solvent to solid, and extraction temperature at 300 W,
      4 min, 35 (mL/g), and 70  degrees C respectively. The crude extract was
      successively purified by chromatography, yielding two major polysaccharide
      fractions, termed Fr-I and Fr-II. Both fractions are heteropolysaccharides,
      mainly containing glucose, mannose, and allose with an a-configuration. Thermo
      gravimetric analysis (TGA) indicated that the degradation temperatures (Td) of Fr
      I and Fr-II were 185  degrees C and 190  degrees C respectively. The preliminary
      antioxidant activity test in vitro showed both fractions could potentialize the
      scavenging effect on hydroxyl and DPPH radicals in a dose-dependent manner. In
      conclusion, the two polysaccharides may be useful as naturally potential
      antioxidant agents for application in food and medicinal fields. 

PMID- 24096656
TI  - Mechanical wounding of yeast-like conidium cells of Tremella fuciformis makes
      them susceptible to Agrobacterium-mediated transformation.
AB  - We developed an efficient protocol that makes possible the practical use of
      Agrobacterium to transform the yeast-like conidia of Tremella fuciformis.
      Mechanical wounding of fungal cells prior to co-cultivation with Agrobacterium
      cells greatly improved transformation efficiency. 

PMID- 24096657
TI  - Polishing properties of sake rice Koshitanrei for high-quality sake brewing.
AB  - The Japanese high-quality sake Daiginjo-shu is made from highly polished rice
      (polishing ratio, less than 50%). Here we showed that the sake rice Koshitanrei
      (KOS) has an excellent polishing property. Rice grains of KOS had the same lined
      white-core region as the sake rice Yamadanishiki (YAM). The grain
      rigidity/hardness of KOS was higher than that of the sake rice Gohyakumangoku
      (GOM). The loss ratio of KOS after high polishing by an industrial polishing
      machine was lower than that of GOM. Further, a clear taste of sake produced from
      KOS was confirmed by sensory evaluation. 

PMID- 24096658
TI  - Improvement of reticuline productivity from dopamine by using engineered
      Escherichia coli.
AB  - Benzylisoquinoline alkaloids (BIAs) are pharmaceutically important compounds. We
      have previously devised a reticuline (BIA) production method from dopamine by
      using Escherichia coli; however, its productivity was relatively low (33 uM, 11
      mg/L). We report here, by fine-tuning the method, higher reticuline productivity
      of 165 uM (54 mg/L), increasing the conversion efficiency by 8-fold. These
      results are important for developing an efficient route to fermentative
      reticuline production. 

PMID- 24096659
TI  - Evidence of antagonistic regulation of restart from G(1) delay in response to
      osmotic stress by the Hog1 and Whi3 in budding yeast.
AB  - Hog1 of Saccharomyces cerevisiae is activated by hyperosmotic stress, and this
      leads to cell-cycle delay in G1, but the mechanism by which cells restart from G1
      delay remains elusive. We found that Whi3, a negative regulator of G1 cyclin,
      counteracted Hog1 in the restart from G1 delay caused by osmotic stress. We have
      found that phosphorylation of Ser-568 in Whi3 by RAS/cAMP-dependent protein
      kinase (PKA) plays an inhibitory role in Whi3 function. In this study we found
      that the phosphomimetic Whi3 S568D mutant, like the Deltawhi3 strain, slightly
      suppressed G1 delay of Deltahog1 cells under osmotic stress conditions, whereas
      the non-phosphorylatable S568A mutation of Whi3 caused prolonged G1 arrest of
      Deltahog1 cells. These results indicate that Hog1 activity is required for
      restart from G1 arrest under osmotic stress conditions, whereas Whi3 acts as a
      negative regulator for this restart mechanism. 

PMID- 24096660
TI  - Genetic organization of two types of flounder warm-temperature acclimation
      associated 65-kDa protein and their gene expression profiles.
AB  - We isolated and characterized two cDNA clone encoding warm-temperature
      acclimation-associated 65-kDa proteins (PoWap65-1 and PoWap65-2) from the olive
      flounder, Paralichthys olivaceus. The deduced amino acid sequences of PoWap65s
      showed overall identities of 33-73% with other fish Wap65 and mammalian hemopexin
      like proteins. The 5'-flanking regions of both PoWap65-encoding genes contained
      various putative transcriptional elements. While PoWap65-1 and PoWap65-2 were
      structurally similar, they exhibited highly differential patterns of expression.
      PoWap65-1 was expressed only in the liver, whereas PoWap65-2 transcripts were
      detected in a wide range of tissues. The accumulation of PoWap65s mRNA was
      expressed differentially during development. Expression of them in warm
      temperatures also differed in flounder embryonic cells. PoWap65-1 was upregulated
      by temperature stimulation whereas PoWap65-2 was not detected. PoWap65s were
      highly regulated by Edwardsiella tarda infection and hypoxia. Pathogen challenge
      induced PoWap65-2 expression in the liver whereas PoWap65-1 was downregulated.
      Hypoxia induced the expression of both PoWap65s in the liver of juvenile fish. 

PMID- 24096661
TI  - Steely enzymes are involved in prestalk and prespore pattern formation.
AB  - 4-Methyl-5-pentylbenzene-1,3-diol (MPBD), a product of SteelyA enzyme, controls
      Dictyostelium spore maturation. Since the expression of stlA split the in early
      and terminal stages, we cannot exclude the possibility that MPBD regulates spore
      differentiation from the early stage by creating a bias between the cells. 1-(3,5
      Dichloro-2,6-dihydroxy-4-methoxyphenyl) hexan-1-on (DIF-1), a product of SteelyB,
      was identified as the major stalk cell inducer by in vitro assay, but in vivo
      assay revealed that DIF-1 induces only prestalkB (pstB) and prestalkO (pstO)
      cells and, that the major prestalkA (pstA) cells differentiated without DIF-1. In
      order to determine mechanism of polyketide regulated pattern formation, we
      examined the spatial expression patterns of prestalk and prespore markers in stlA
      and stlB knockout mutants. We found that MPBD regulates spore maturation at the
      culmination stage. We also found that the stlA and stlB double-knockout mutant
      lost pstA marker gene expression. 

PMID- 24096662
TI  - Possible involvement of Mycoplasma hominis in inhibiting the formation of
      biofilms by uropathogenic Escherichia coli (UPEC).
AB  - Here we examined the involvement of Mycoplasma hominis in the formation of
      biofilms by uropathogenic Escherichia coli (UPEC) strain CFT073. Initially, we
      thought that M. hominis does not affect the fitness of UPEC, including the growth
      and production of signaling molecules, such as autoinducer-2 and indole. We
      found, however, that the presence of M. hominis significantly decreased the
      degree of biofilm formation by UPEC CFT073 (approximately a 60% reduction for
      10(5) ccu/mL of M. hominis as compared with UPEC alone). We also found that it
      had a slight effect in inhibiting the attachment and cytotoxicity of UPEC CFT073.
      These findings are specific to these UPEC strains rather than to
      enterohemorrhagic E. coli (EHEC) strains, found in normal intestinal flora. In
      addition, we performed whole-transcriptome profiling and quantitative real-time
      polymerase chain reaction (qRT-PCR) analysis. This indicated that the PhoPQ
      system and the anti-termination protein (encoded by ybcQ) were involved in the
      reduction of biofilm formation by M. hominis (corroborated by qRT-PCR).
      Furthermore, our results indicate that M. hominis raises the degree of
      transcription of toxin genes, including hha and pasT. Hence, we suggest a
      possible role of M. hominis in affecting the formation of biofilms by UPEC in the
      urinary tract. 

PMID- 24096663
TI  - Novel exopolysaccharides produced by Lactococcus lactis subsp. lactis, and the
      diversity of epsE genes in the exopolysaccharide biosynthesis gene clusters.
AB  - To characterize novel variations of exopolysaccharides (EPSs) produced by dairy
      strains of Lactococcus lactis subsp. lactis and subsp. cremoris, the EPSs of five
      dairy strains of L. lactis were purified. Sugar composition analysis showed two
      novel EPSs produced by strains of L. lactis subsp. lactis. One strain produced
      EPS lacking galactose, and the other produced EPS containing fucose. Among the
      eps gene clusters of these strains, the highly conserved epsD and its neighboring
      epsE were sequenced. Sequence and PCR analysis revealed that epsE genes were
      strain-specific. By Southern blot analysis using epsD, the eps gene cluster in
      each strain was found to locate to the chromosome or a very large plasmid. This
      is the first report on the identification of two novel EPSs in L. lactis subsp.
      lactis. The strains can be detected among other strains by using epsE genes
      specific to them. 

PMID- 24096664
TI  - Tumor suppressor candidate TUSC3 expression during rat testis maturation.
AB  - Analysis of microarray data obtained by comparing gene expression between 2-week
      old infant and 7-week-old mature SD rat testes revealed novel targets involved in
      tumor suppression. Reverse-transcription polymerase chain reaction and Northern
      blotting indicated that Tusc3 gene expression was upregulated in the normal
      maturing testis and prostate and other organs such as the cerebrum and ovary.
      Tumor suppressor candidate 3 protein expression was detected in these same organs
      at a size of about 40 kDa, in accord with the predicted molecular size. In situ
      hybridization and immunohistochemistry showed that mRNA and protein localization
      were prevalent in the testis spermatocytes and interstitial cells such as the
      Leydig cells, as well as prostate epithelial cells. These data suggest that TUSC3
      is deeply involved in spermatogenesis in the testis, inducing sperm
      differentiation and maturation, and plays a role in normal prostate development
      and tumor suppression. 

PMID- 24096665
TI  - Strategies to decolorize high concentrations of methyl orange using growing cells
      of Lactobacillus casei TISTR 1500.
AB  - Batch, fed-batch, and continuous fermentation was used in the processing of
      methyl orange decolorization using growing cells of Lactobacillus casei TISTR
      1500. This report presents the optimal conditions for methyl orange
      decolorization by the strain TISTR 1500 in modified MRS via a central composite
      design (CCD) experiment. In particular, the highest decolorization efficiencies
      were obtained with 13.41 g/L of meat extract, and with 10.89 g/L of yeast extract
      at pH 6.88 at 35  degrees C. Under the optimal conditions, the rate of
      decolorization increased to 322% of that obtained for un-optimized MRS medium.
      The high concentration of methyl orange (5 g/L) was completely degraded within 9
      h in batch fermentation. The total methyl orange load with 8.075 g/L was also
      decolorized in fed-batch fermentation within 13 h, and the biomass of the strain
      dramatically decreased after an incubation time of 8 h due to a shortage of
      sucrose. In the continuous system with a dye-loading rate of 600 mg/L/h and a
      total of loaded azo dye of 7.2 g/L, high efficiency of methyl orange removal was
      significantly high, at 98%. 

PMID- 24096666
TI  - Functional analysis of the AKR4C subfamily of Arabidopsis thaliana: model
      structures, substrate specificity, acrolein toxicity, and responses to light and
      [CO(2)].
AB  - In Arabidopsis thaliana, the aldo-keto reductase (AKR) family includes four
      enzymes (The AKR4C subfamily: AKR4C8, AKR4C9, AKR4C10, and AKR4C11). AKR4C8 and
      AKR4C9 might detoxify sugar-derived reactive carbonyls (RCs). We analyzed AKR4C10
      and AKR4C11, and compared the enzymatic functions of the four enzymes. Modeling
      of protein structures based on the known structure of AKR4C9 found an
      (alpha/beta)8-barrel motif in all four enzymes. Loop structures (A, B, and C)
      which determine substrate specificity, differed among the four. Both AKR4C10 and
      AKR4C11 reduced methylglyoxal. AKR4C10 reduced triose phosphates,
      dihydroxyacetone phosphate (DHAP), and glyceraldehydes 3-phosphate (GAP), the
      most efficiently of all the AKR4Cs. Acrolein, a lipid-derived RC, inactivated the
      four enzymes to different degrees. Expression of the AKR4C genes was induced
      under high-[CO2] and high light, when photosynthesis was enhanced and
      photosynthates accumulated in the cells. These results suggest that the AKR4C
      subfamily contributes to the detoxification of sugar-derived RCs in plants. 

PMID- 24096667
TI  - Nucleosome distribution near the 3' ends of genes in the human genome.
AB  - By systematic analysis of high-throughput sequencing datasets from the human
      genome, we found that protein-coding genes have a specific chromatin structure
      near transcription termination sites relative to non-coding genes, one related to
      polyadenylation. Nucleosome was depleted near the site of
      cleavage/polyadenylation (polyA site) regardless of its relative position in the
      gene. DNA sequence plays an improtant role in nucleosome distribution, and
      conservative sequence elements and the protein binding to them are major
      determinants in causing nucleosome depletion near polyA sites. Furthermore,
      nucleosome occupancy was regulated by gene transcription and RNA polymerase II
      (RNAPII) occupancy. Our results reveal influences on nucleosome occupancy near
      polyadenylation sites and constitute evidence indicating that nucleosome
      distribution regulates 3' end processing of protein-coding genes. 

PMID- 24096668
TI  - Molecular cloning and characterization of cystatin, a cysteine protease
      inhibitor, from bufo melanostictus.
AB  - Cystatins are efficient inhibitors of papain-like cysteine proteinases, and they
      serve various important physiological functions. In this study, a novel cystatin,
      Cystatin-X, was cloned from a cDNA library of the skin of Bufo melanostictus. The
      single nonglycosylated polypeptide chain of Cystatin-X consisted of 102 amino
      acid residues, including seven cysteines. Evolutionary analysis indicated that
      Cystatin-X can be grouped with family 1 cystatins. It contains cystatin-conserved
      motifs known to interact with the active site of cysteine proteinases.
      Recombinant Cystatin-X expressed and purified from Escherichia coli exhibited
      obvious inhibitory activity against cathepsin B. rCystatin-X at a concentration
      of 8 uM inhibited nearly 80% of cathepsin B activity within 15 s, and about 90%
      of cathepsin B activity within 15 min. The Cystatin-X identified in this study
      can play an important role in host immunity and in the medical effect of B.
      melanostictus. 

PMID- 24096669
TI  - Immobilization of an esterase inhibitor on a porous hollow-fiber membrane by
      radiation-induced graft polymerization for developing a diagnostic tool for
      feline kidney diseases.
AB  - Removal of the major urinary protein, cauxin, a carboxylesterase, from cat urine
      is essential for distinguishing between physiological and abnormal proteinuria by
      a urine dipstick. We have previously developed a material for removing cauxin by
      using lens culinaris agglutinin (LCA) lectin which targets the N-linked
      oligosaccharides present in cauxin. To improve the affinity and specificity
      toward cauxin, we immobilized 1,1,1-trifluoro-3-(2-sulfanylethylsulfanyl) propane
      2-one, an inhibitor of esterases, to a polymer chain grafted on to a porous
      hollow-fiber membrane by applying radiation-induced graft polymerization. Normal
      male urine was forced to permeate through the pores rimmed by the ligand
      immobilized polymer chain. Cauxin could not be detected in the effluent from the
      membrane. The residence time of the urine across a membrane thickness of 1 mm was
      set at 7 s. The respective dynamic and equilibrium binding capacities of the
      membrane for cauxin were 2 and 3 mg/g. The developed cauxin-affinity membrane
      material was more effective for diagnosing cat kidney diseases than the LCA
      lectin tip. 

PMID- 24096670
TI  - Identification of laboratory-specific variations of Bacillus subtilis strains
      used in Japan.
AB  - The strain of Bacillus subtilis 168 used in laboratories in Japan was distributed
      in the 1990s when the sequencing consortium commenced operations. After 20 years
      of use of B. subtilis 168 in many laboratories, observations of variations in
      growth phenotypes have been reported. In this study, to uncover laboratory
      specific variations of B. subtilis 168 strains in Japan, we re-sequenced 11 B.
      subtilis 168 strains from nine laboratories and analyzed how their genomes
      differed. We found that the 168 strains from different laboratories differed by 1
      7 variations. These variations might have been caused by differences in storage
      conditions in the laboratories or differences among colonies of the original
      stock. Based on our results, researchers ought to understand the genetic
      differences among wild-type (parental) strains in different laboratories and the
      reference strain by re-sequencing analysis, and ought to pay more attention to
      the management of laboratory strains. 

PMID- 24096671
TI  - Degradation of beta-conglycinin beta-homotrimer by papain: independent occurrence
      of limited and extensive proteolysis.
AB  - Limited and extensive proteolysis occur when beta-conglycinin beta homo-trimer
      (beta(3)-conglycinin) from soybeans is attacked by papain. Slow limited
      proteolysis is restricted to cleavage of beta(3)-conglycinin polypeptides into
      subunit halves (N- and C-terminal domains) that are further slightly truncated.
      The kinetics of limited and extensive proteolyses analyzed separately indicates
      that the two processes occur independently from the very beginning of the
      reaction. In contrast, limited proteolysis of phaseolin from common beans has
      been found to be prerequisite for the onset of its extensive proteolysis. The
      dramatic distinction between the degradation patterns of beta(3)-conglycinin and
      phaseolin, homologous storage 7S globulins, suggests the existence of intrinsic
      differences in their structures. This hypothesis is supported by comparative
      analysis of the accessibilities to the solvent of amino acid residues in
      phaseolin and beta(3)-conglycinin structures, which indicated the relatively low
      packing density of the latter, resulting in enhanced susceptibility of it to
      extensive proteolysis.

PMID- 24096672
TI  - Biosynthetic mechanism for L-Gulose in main polar lipids of Thermoplasma
      acidophilum and possible resemblance to plant ascorbic acid biosynthesis.
AB  - L-Gulose is a very rare sugar, but appears as a sugar component of the main polar
      lipids characteristic in such a thermophilic archaeon as Thermoplasma acidophilum
      that lives without cell walls in a highly acidic environment. The biosynthesis of
      L-gulose in this thermophilic organism was investigated with deuterium-labeling
      experiments. L-Gulose was found to be biosynthesized from D-glucose via stepwise
      stereochemical inversion at C-2 and C-5. The involvement of an epimerase related
      to GDP-mannose 3,5-epimerase, the key enzyme of plant ascorbate biosynthesis, was
      also suggested in this C-5 inversion. The resemblance of L-gulose biosynthesis in
      archaea and plants might be suggested from these results. 

PMID- 24096673
TI  - Lignan glucosides from Sinomenium acutum rhizomes.
AB  - The new lignan glucoside, acutumoside (1), was isolated from Sinomenium acutum
      rhizomes together with nine known compounds (2-10). The structure of 1 was
      elucidated on the basis of extensive spectroscopic analyses, including two
      dimensional nuclear magnetic resonance and chemical reactions. Compounds 2, 7, 8,
      and 10 displayed potential antiproliferative activity against A549, SK-OV-3, SK
      MEL-2, and HCT-15 cell lines, while compound 1 showed weak activity against these
      human tumor cells. 

PMID- 24096674
TI  - Improved detection of di-peptides by liquid chromatography-tandem mass
      spectrometry with 2,4,6-trinitrobenzene sulfonate conversion.
AB  - Highly sensitive detection of small peptides at the pM level was achieved by
      liquid chromatography-multiple reaction monitoring-tandem mass spectrometry (LC
      MRM-MS/MS) in combination with the 2,4,6-trinitrobenzene sulfonate (TNBS)
      conversion technique. Six di-peptides having Tyr at the C-terminal (i.e., Gly
      Tyr, Val-Tyr, Met-Tyr, Glu-Tyr, Lys-Tyr and His-Tyr) were subjected to the TNBS
      MRM analysis in this study. The TNBS conversion conditions of pH 8.0, 30  degrees
      C and 60-min incubation enabled the di-peptides to be successfully converted to a
      trinitrophenyl (TNP) form with the mass increment of +212 Da. The proposed TNBS
      MRM method enabled di-peptide detection that was highly improved by a factor of 3
      55 in signal-to-noise ratio due to increased hydrophobicity by the induced TNP
      moiety. The method also permitted highly sensitive detection of di-peptides with
      a detection limit of >54 pM (>1.35 fmol/injection), achieving high
      reproducibility (<5% coefficient of variation) and rapidity (<30 min) by LC-MRM
      MS/MS. 

PMID- 24096675
TI  - Pou2f3/Skn-1a is necessary for the generation or differentiation of solitary
      chemosensory cells in the anterior nasal cavity.
AB  - Solitary chemosensory cells in the non-neuronal epithelium of the anterior nasal
      cavity have bitter taste cell-like molecular characteristics and are involved in
      the detection of noxious substances. Here, we demonstrate that Pou2f3/Skn-1a,
      which is necessary for generation of sweet, umami, and bitter taste cells, is
      also necessary for the generation or differentiation of solitary chemosensory
      cells. 

PMID- 24096676
TI  - The molecular mechanism of calcification in aquatic organisms.
AB  - Biomineralization is a process of mineral deposition by organisms. Calcium salts
      are the major component of various biominerals, calcium carbonate being the
      predominant type in aquatic organisms. The mechanism of biomineralization has
      been conventionally analyzed by microscopic observation. The findings obtained
      suggest that minute amounts of organic matrices in biominerals play a key role in
      biomineralization. We first introduced the methodology of bioactive compound
      chemistry into this research field. Using various biominerals, such as the
      exoskeleton and gastroliths of the crayfish, the otoliths and scales of fish, the
      coccoliths of coccolithophores, bivalve shells, and coral skeleton, a range of
      organic matrices were purified by simple functional assays, and their chemical
      structures were determined. The function of each matrix component was estimated
      by its ability to interact with calcium carbonate and by in vitro
      crystallization, immunological localization, and site-specific and temporal
      expression of the encoding genes in the case of proteins and peptides, among
      other compounds. It was found that there was almost no similarity in chemical
      structure among organic matrices from various biominerals, but similarity in
      function was observed, and that made possible the functional classification of
      organic matrices. 

PMID- 24096677
TI  - Enzymes that control the conversion of L-tryptophan-nicotinamide and the urinary
      excretion ratio (N(1)-methyl-2-pyridone-5-carboxamide + N(1)-methyl-4-pyridone-3
      carboxamide)/N(1)-methylnicotinamide in mice.
AB  - There is little information on L-tryptophan->nicotinamide metabolism in mice. In
      the present study, we investigated the two important nutritional factors involved
      in metabolism L-tryptophan->nicotinamide; one is the amount of nicotinamide
      synthesized from L-tryptophan, and the other is the urine ratio (N(1)-methyl-2
      pyridone-5-carboxamide + N(1)-methyl-4-pyridone-3-carboxamide)/N(1)
      methylnicotinamide. The order of the percentages of nicotinamide synthesized from
      L-tryptophan was as follows: CBA strain mice (conversion percentage 0.41%) < BALB
      strain mice (0.82%) < C57BL/6 strain mice (1.13%) < ICR strain mice (1.70%).
      Urinary excretion of quinolinic acid was correlated with urinary excretion of the
      sum of nicotinamide and its catabolites (p<0.0001). The urine sum, which reflects
      the conversion of L-tryptophan->nicotinamide, correlated well with the activity
      of 3-hydroxyanthranilic acid dioxygenase (p=0.040). A nutritional indicator, the
      urine ratio (N(1)-methyl-2-pyridone-5-carboxamide + N(1)-methyl-4-pyridone-3
      carboxamide)/N(1)-methylnicotinamide, was controlled by the activity of N(1)
      methyl-2-pyridone-5-carboxamide-forming N(1)-methylnicotinamide oxidase.

PMID- 24096678
TI  - Properties of rice stem extracts obtained by using subcritical fluids.
AB  - Rice stems were subjected to a subcritical fluid treatment at 230  degrees C,
      using ethanol or acetone at a dilution of 0-100% in water. The obtained extracts
      were determined for their yield, carbohydrate content, phenolic content, DPPH
      radical scavenging ability, and color. The highest yield and carbohydrate content
      were achieved with the subcritical 20% (v/v) organic solvent, while the highest
      phenolic content was obtained with subcritical 80% (v/v) acetone. The highest
      radical scavenging ability was achieved with subcritical 60% (v/v) ethanol and
      80% (v/v) acetone. The lightness of the extracts obtained with subcritical
      ethanol and acetone was negatively correlation with their radical scavenging
      ability (R=-0.85). The relationship between the lightness and phenolic content of
      the extracts was not significant, suggesting that other substances in the extract
      could also possess radical scavenging ability. 

PMID- 24096679
TI  - Characterization of a glycoside hydrolase family 31 alpha-glucosidase involved in
      starch utilization in Podospora anserina.
AB  - For Podospora anserina, several studies of cellulolytic enzymes have been
      established, but characteristics of amylolytic enzymes are not well understood.
      When P. anserina grew in starch as carbon source, it accumulated glucose,
      nigerose, and maltose in the culture supernatant. At the same time, the fungus
      secreted alpha-glucosidase (PAG). PAG was purified from the culture supernatant,
      and was found to convert soluble starch to nigerose and maltose. The recombinant
      enzyme with C-terminal His-tag (rPAG) was produced with Pichia pastoris. Most
      rPAG produced under standard conditions lost its affinity for nickel-chelating
      resin, but the affinity was improved by the use of a buffered medium (pH 8.0)
      supplemented with casamino acid and a reduction of the cultivation time. rPAG
      suffered limited proteolysis at the same site as the original PAG. A site
      directed mutagenesis study indicated that proteolysis had no effect on enzyme
      characteristics. A kinetic study indicated that the PAG possessed significant
      transglycosylation activity. 

PMID- 24096680
TI  - Pyrosequencing analysis of microbiota in Kaburazushi, a traditional medieval
      sushi in Japan.
AB  - The processing of archetypal Japanese sushi involves microbial fermentation. The
      traditional sushi kaburazushi, introduced in the middle ages, is made by
      fermenting salted yellow tail, salted turnip, and malted rice, and is
      distinguished from the ancient sushi narezushi, made from fish and boiled rice.
      In this study, we examined changes in the microbial population during kaburazushi
      fermentation by pyrosequencing the 16S ribosomal RNA genes (rDNA) of the
      organisms in the fermentation medium. Ribosomal Database Project Classifier
      analysis identified 31 genera, among which Lactobacillus drastically increased
      during fermentation (150-fold increment over 8 d), while the relative populations
      of the other gram-positive bacteria (Staphylococcus and Bacillus) decreased.
      Basic Local Alignment Search Tool analysis revealed the dominant species to be L.
      sakei. This organism constituted approximately 90% of Lactobacillus and 79% of
      total microbiota. The taxonomic diversity and species richness (assayed by
      Shannon-Weiner Index and Chao 1, respectively) were not significantly different
      between middle-ages kaburazushi and ancient narezushi. Both types were
      characterized by the preferential growth of Lactobacillales. 

PMID- 24096681
TI  - Enhanced reactivity of graphene wrinkles and their function as nanosized gas
      inlets for reactions under graphene.
AB  - Formation of wrinkles at graphene/Pt(111) surface was investigated by low energy
      electron microscopy (LEEM). Reversible wrinkling and unwrinkling of graphene
      sheets were observed upon cycled heating and cooling treatments, exhibiting a
      hysteresis effect with the temperature. In situ LEEM studies of graphene
      oxidation show preferential oxidation of the wrinkles than flat graphene sheets
      and graphene edges. The function of the wrinkles as one-dimensional (1D)
      nanosized gas inlets for oxygen and the strain at the distorted sp(2)-hybridized
      carbon atoms of the wrinkle sites can be attributed to the enhanced reactivity of
      wrinkles to the oxidation. Meanwhile, wrinkles also served as nanosized gas
      inlets for oxidation of CO intercalated between graphene and Pt(111). Considering
      that wrinkles are frequently present in graphene structures, the role of wrinkles
      as 1D reaction channels and their enhanced reactivity to reactions may have an
      important effect on graphene chemistry. 

PMID- 24096682
TI  - Thyrotroph hyperplasia.

PMID- 24096683
TI  - Pharmacokinetics of dolutegravir in HIV-seronegative subjects with severe renal
      impairment.
AB  - PURPOSE: Dolutegravir (DTG), an unboosted HIV integrase inhibitor (INI), is
      metabolized by UGT1A1 and to a minor extent by CYP3A. Renal elimination of
      unchanged DTG is very low (< 1 %). As renal impairment may affect
      pharmacokinetics (PK), even for drugs primarily metabolized or secreted in bile,
      this study investigated the effect of renal impairment on the PK of DTG. METHODS:
      This was an open-label, single-dose study of oral DTG 50 mg administered to
      subjects with severe renal impairment (creatinine clearance [CLcr] <30 mL/min;
      not on dialysis) and to healthy controls (CLcr >90 mL/min) matched for gender,
      age and body mass index (8 subjects per group). Serial PK samples were collected
      up to 72 h post-dose for determination of DTG and DTG-glucuronide (DTG-Gluc)
      concentrations in plasma. DTG unbound fraction in plasma was determined at 3 and
      24 h. PK parameters were determined by non-compartmental methods and compared
      between groups by analysis of covariance. RESULTS: DTG was well tolerated with a
      low incidence of Grade 1 adverse events. DTG PK parameters showed significant
      overlap between groups. DTG mean exposure was lower in subjects with severe renal
      impairment compared to healthy, matched subjects: AUC(0-infinity) and Cmax were
      40 % and 23 % lower, while mean DTG-Gluc was increased. Renal impairment did not
      affect DTG fraction unbound in plasma. CONCLUSIONS: The modest reductions in mean
      PK exposures for DTG and increases for DTG-Gluc in the severe renal impairment
      group are not considered clinically significant. DTG does not require dose
      adjustment in patients with renal impairment.

PMID- 24096684
TI  - Sex differences in spontaneous reports on adverse bleeding events of
      antithrombotic treatment.
AB  - PURPOSE: To explore if sex differences are found in spontaneously reported
      adverse events for clopidogrel, low-dose aspirin and warfarin treatment in
      routine care. METHODS: A cross-sectional analysis combining data on bleeding
      events from the Swedish Spontaneous Adverse Drug Event Reporting System (SWEDIS)
      with data from the National Prescribed Drug register. Bleeding event reports from
      1999 to 2010 and 2005 to 2010 were adjusted to the number of prescriptions and
      the number of exposed patients respectively among women and men. Co-medication
      and co-prescription were analysed. RESULTS: More men were dispensed clopidogrel
      although the reported bleeding event risk after adjustment for number of patients
      exposed was higher in women (RR 1.40; 95 % CI, 1.00-1.96). The difference
      disappeared when adjusting for the number of prescriptions (RR 0.99; 95 % CI,
      0.71-1.39). The reported bleeding event risk with low-dose aspirin was lower in
      women, adjusted for patients exposed (RR 0.80; 95 % CI, 0.66-0.97). For warfarin,
      no sex difference in bleeding event reports could be found (RR 1.01; 95 % CI,
      0.87-1.17). CONCLUSIONS: This ecological comparison of bleeding reports and
      dispensed prescriptions showed a signal towards a higher prevalence of bleeding
      reports in women on clopidogrel treatment while the opposite was found for low
      dose aspirin. For warfarin, no significant sex difference was seen regarding
      bleeding event reports, suggesting individualised dosing being an important
      factor. Men were more commonly prescribed antithrombotic combinations, and this
      was reflected by a larger proportion of bleeding reports including more than one
      antithrombotic agent.

PMID- 24096685
TI  - Management of type 2 diabetes mellitus in older patients: current and emerging
      treatment options.
AB  - Elderly patients with type 2 diabetes mellitus (T2DM) are a rapidly emerging
      population that presents unique clinical challenges. This diverse patient group
      can differ widely in terms of physical and mental status, which can increase
      their risk of complications including hypoglycemia, falls, and depression. These
      factors can negatively impact their glycemic control, safety, and quality of
      life. The risk of hypoglycemic events is elevated among elderly patients with
      diabetes. In many cases, these events are related to antidiabetic therapy and the
      pursuit of strict glycemic control. Fear of a hypoglycemic episode, on the part
      of the patient and/or healthcare provider, is another major barrier to achieving
      glycemic control. Hypoglycemic events, even in the absence of awareness of the
      event (asymptomatic), can have negative consequences. To help manage these risks,
      several national and international organizations have proposed guidelines to
      address individualized treatment goals for older adults with diabetes. This
      article reviews current treatment guidelines for setting glycemic targets in
      elderly patients with T2DM, and discusses the role of emerging treatment options
      in this patient population. 

PMID- 24096686
TI  - Loss mitigation in plasmonic solar cells: aluminium nanoparticles for broadband
      photocurrent enhancements in GaAs photodiodes.
AB  - We illustrate the important trade-off between far-field scattering effects, which
      have the potential to provide increased optical path length over broad bands, and
      parasitic absorption due to the excitation of localized surface plasmon
      resonances in metal nanoparticle arrays. Via detailed comparison of photocurrent
      enhancements given by Au, Ag and Al nanostructures on thin-film GaAs devices we
      reveal that parasitic losses can be mitigated through a careful choice of
      scattering medium. Absorption at the plasmon resonance in Au and Ag structures
      occurs in the visible spectrum, impairing device performance. In contrast,
      exploiting Al nanoparticle arrays results in a blue shift of the resonance,
      enabling the first demonstration of truly broadband plasmon enhanced photocurrent
      and a 22% integrated efficiency enhancement. 

PMID- 24096687
TI  - Progress amidst some anticipated growing pains for PCCM.

PMID- 24096688
TI  - Engineering a control system for hypoglycemia prevention, detection, and
      intervention in critical care*.

PMID- 24096689
TI  - Pediatric out-of-hospital cardiac arrest-are we behind the times?*.

PMID- 24096690
TI  - Chilled to the marrow: neonatal brain injury, hypothermia, and the immune
      system*.

PMID- 24096691
TI  - Human beta 2 defensin-is it about prediction or is it about the science? A tale
      of innate immunity*.

PMID- 24096692
TI  - Validity of family satisfaction measures: an ongoing process*.

PMID- 24096693
TI  - Quality of care leads to quality of life after trauma in children*.

PMID- 24096694
TI  - Is the shock index useful in children?*.

PMID- 24096695
TI  - The sicker the patient the higher the lactate: a well-known relationship*.

PMID- 24096696
TI  - Neonatal endotracheal intubation: what is the midtracheal position?

PMID- 24096697
TI  - Selective anticancer agents suppress aging in Drosophila.
AB  - Mutations of the PI3K, TOR, iNOS, and NF-kappaB genes increase lifespan of model
      organisms and reduce the risk of some aging-associated diseases. We studied the
      effects of inhibitors of PI3K (wortmannin), TOR (rapamycin), iNOS (1400W), NF
      kappaB (pyrrolidin dithiocarbamate and QNZ), and the combined effects of
      inhibitors: PI3K (wortmannin) and TOR (rapamycin), NF-kappaB (pyrrolidin
      dithiocarbamates) and PI3K (wortmannin), NF-kappaB (pyrrolidine dithiocarbamates)
      and TOR (rapamycin) on Drosophila melanogaster lifespan and quality of life
      (locomotor activity and fertility). Our data demonstrate that pharmacological
      inhibition of PI3K, TOR, NF-kappaB, and iNOS increases lifespan of Drosophila
      without decreasing quality of life. The greatest lifespan expanding effect was
      achieved by a combination of rapamycin (5 MUM) and wortmannin (5 MUM) (by 23.4%).
      The bioinformatic analysis (KEGG, REACTOME.PATH, DOLite, and GO.BP) showed the
      greatest aging-suppressor activity of rapamycin, consistent with experimental
      data. 

PMID- 24096699
TI  - Therapeutic exploration of betulinic acid in chemically induced hypothyroidism.
AB  - Hypothyroidism is a chronic condition characterized by abnormally low thyroid
      hormone production. The decreased serum level (>5.1 mIU/l) of thyroid-stimulating
      hormone (TSH) in blood indicates hypothyroidism. The study was an attempt to
      access the effect of betulinic acid on chemically induced hypothyroidism in
      female albino rats. Betulinic acid is a naturally occurring pentacyclic
      triterpenoid, which has antiretroviral, antimalarial, and anti-inflammatory
      properties, as well as anticancer potential, by inhibiting topoisomerase.
      Hypothyroidism was induced in female albino rats using propylthiouracil (PTU) at
      a dose of 60 MUg/kg body weight orally for 1 month. Induction of hypothyroidism
      was confirmed by increased TSH level. At the end of second month, blood was
      collected, centrifuged and serum was analyzed for TSH, T3, and T4 level and
      protocol was terminated by killing of animals. The animals exposed to PTU were
      treated with pure standard drug thyroxine at a dose of 10 MUg/kg of body weight
      by oral route and the test drug betulinic acid 20 mg/kg by oral route through
      force feeding in their respective groups. Treatment was carried out for a period
      of 2 months. Group with PTU-induced hypothyroidism showed an elevation in serum
      TSH and reduction level, which was restored by the betulinic acid in treated
      female albino rats. Betulinic acid also reduced the damage caused in the thyroid
      tissues by PTU, thus minimizing the symptoms of hypothyroidism. Histopathological
      examinations of the thyroid tissue showed changes in the thyrocytes of PTU
      treated group while thyroxine group showed normal thyroid follicles cell
      architecture and the group treated with betulinic acid also showed marked
      improvement in the follicles integrity which shows that betulinic acid has some
      protective activity. This study shows that the betulinic acid has thyroid
      enhancing potential by lowering down the TSH levels and reducing the damage
      caused in the thyroid tissues, thus minimizing the symptoms of hypothyroidism
      when used anaphylactically in rats. 

PMID- 24096698
TI  - Genome-wide association study of endometrial cancer in E2C2.
AB  - Endometrial cancer (EC), a neoplasm of the uterine epithelial lining, is the most
      common gynecological malignancy in developed countries and the fourth most common
      cancer among US women. Women with a family history of EC have an increased risk
      for the disease, suggesting that inherited genetic factors play a role. We
      conducted a two-stage genome-wide association study of Type I EC. Stage 1
      included 5,472 women (2,695 cases and 2,777 controls) of European ancestry from
      seven studies. We selected independent single-nucleotide polymorphisms (SNPs)
      that displayed the most significant associations with EC in Stage 1 for
      replication among 17,948 women (4,382 cases and 13,566 controls) in a multiethnic
      population (African America, Asian, Latina, Hawaiian and European ancestry), from
      nine studies. Although no novel variants reached genome-wide significance, we
      replicated previously identified associations with genetic markers near the HNF1B
      locus. Our findings suggest that larger studies with specific tumor
      classification are necessary to identify novel genetic polymorphisms associated
      with EC susceptibility. 

PMID- 24096701
TI  - Viewpoint on handling anti-TNF failure in psoriasis.
AB  - An association among the occurrence of antidrug antibodies (ADAs), diminished
      trough serum drug levels (TSDLs) and non-response or loss of response has been
      described for several tumor necrosis factor alpha (TNF) blocking agents in a
      variety of diseases, including psoriasis. In a series of ten psoriasis patients
      with primary or secondary failure, or adverse reactions during anti-TNF therapy,
      we measured ADAs and TSDLs in patient serum using radioimmunoassay and ELISA,
      respectively. By proposing a treatment algorithm derived from research in this
      field, we show that measuring ADAs and TSDLs in psoriasis patients provides a
      more structured approach to clinical decision making for psoriasis patients who
      fail anti-TNF therapy. 

PMID- 24096702
TI  - Extensive postzygotic mosaicism for a novel keratin 10 mutation in epidermolytic
      ichthyosis.

PMID- 24096700
TI  - Association of heat-shock proteins in various neurodegenerative disorders: is it
      a master key to open the therapeutic door?
AB  - A number of acute and chronic neurodegenerative disorders are caused due to
      misfolding and aggregation of many intra- and extracellular proteins. Protein
      misfolding and aggregation processes in cells are strongly regulated by cellular
      molecular chaperones known as heat-shock proteins (Hsps) that include Hsp60,
      Hsp70, Hsp40, and Hsp90. Recent studies have shown the evidences that Hsps are
      colocalized in protein aggregates in Alzheimer's disease (AD), Parkinson's
      disease (PD), Polyglutamine disease (PGD), Prion disease, and other
      neurodegenerative disorders. This fact indicates that Hsps might have attempted
      to prevent aggregate formation in cells and thus to suppress disease conditions.
      Experimental findings have already established in many cases that selective
      overexpression of Hsps like Hsp70 and Hsp40 prevented the disease progression in
      various animal models and cellular models. However, recently, various Hsp
      modulators like geldanamycin, 17-(dimethylaminoethylamino)-17
      demethoxygeldanamycin, and celastrol have shown to up-regulate the expression
      level of Hsp70 and Hsp40, which in turn triggers the solubilization of diseased
      protein aggregates. Hsps are, therefore, if appropriately selected, an attractive
      choice for therapeutic targeting in various kinds of neurodegeneration and hence
      are expected to have strong potential as therapeutic agents in suppressing or
      curing AD, PD, PGD, and other devastative neurodegenerative disorders. In the
      present review, we report the experimental findings that describe the implication
      of Hsps in the development of neurodegeneration and explore the possibility of
      how Hsps can be used directly or as a target by other agents to prevent various
      neurodegeneration through preventing aggregation process and thus reducing the
      toxicity of the oligomers based on the previous reports. 

PMID- 24096703
TI  - Positive affect and learning: exploring the "Eureka Effect" in dogs.
AB  - Animals may experience positive affective states in response to their own
      achievements. We investigated emotional responses to problem-solving in dogs,
      separating these from reactions to rewards per se using a yoked control design.
      We also questioned whether the intensity of reaction would vary with reward type.
      We examined the response (behavior and heart rate) of dogs as they learned to
      gain access to different rewards: (1) food (2) human contact, and (3) dog
      contact. Twelve beagles were assigned to matched pairs, and each dog served as
      both an experimental and a control animal during different stages of the
      experiment. We trained all dogs to perform distinct operant tasks and exposed
      them to additional devices to which they were not trained. Later, dogs were
      tested in a new context. When acting as an experimental dog, access to the reward
      was granted immediately upon completion of trained operant tasks. When acting as
      a control, access to the reward was independent of the dog's actions and was
      instead granted after a delay equal to their matched partner's latency to
      complete their task. Thus, differences between the two situations could be
      attributed to experimental dogs having the opportunity to learn to control access
      to the reward. Experimental dogs showed signs of excitement (e.g., increased tail
      wagging and activity) in response to their achievements, whereas controls showed
      signs of frustration (e.g., chewing of the operant device) in response to the
      unpredictability of the situation. The intensity of emotional response in
      experimental dogs was influenced by the reward type, i.e., greatest response to
      food and least to another dog. Our results suggest that dogs react emotionally to
      problem-solving opportunities and that tail wagging may be a useful indicator of
      positive affective states in dogs.

PMID- 24096704
TI  - Triggering social interactions: chimpanzees respond to imitation by a humanoid
      robot and request responses from it.
AB  - Even the most rudimentary social cues may evoke affiliative responses in humans
      and promote social communication and cohesion. The present work tested whether
      such cues of an agent may also promote communicative interactions in a nonhuman
      primate species, by examining interaction-promoting behaviours in chimpanzees.
      Here, chimpanzees were tested during interactions with an interactive humanoid
      robot, which showed simple bodily movements and sent out calls. The results
      revealed that chimpanzees exhibited two types of interaction-promoting behaviours
      during relaxed or playful contexts. First, the chimpanzees showed prolonged
      active interest when they were imitated by the robot. Second, the subjects
      requested 'social' responses from the robot, i.e. by showing play invitations and
      offering toys or other objects. This study thus provides evidence that even
      rudimentary cues of a robotic agent may promote social interactions in
      chimpanzees, like in humans. Such simple and frequent social interactions most
      likely provided a foundation for sophisticated forms of affiliative communication
      to emerge.

PMID- 24096705
TI  - Socio-spatial cognition in vervet monkeys.
AB  - Safety in numbers is thought to be the principal advantage of living in groups
      for many species. The group can only provide protection against predators,
      however, when group cohesion is maintained. Vocalisations are used to monitor
      inter-individual distances, especially under conditions of poor visibility, but
      should be avoided in the presence of predators. Mentally tracking the movements
      of silent and invisible group members would allow animals foraging in dense
      vegetation to stay close to their group members while reducing the use of vocal
      contact. We tested the socio-spatial cognitive abilities of wild vervet monkeys
      (Chlorocebus pygerythrus) by comparing their reactions to plausible and
      implausible displacements of group members simulated by sound playbacks. Our
      methods are comparable to those used in studies of 'object permanence' and
      'invisible displacements' of inanimate objects. Our results show that vervets can
      track the whereabouts of invisibly and silently moving group members, at least
      over short periods of time.

PMID- 24096706
TI  - Life-threatening diphenhydramine toxicity presenting with seizures and a wide
      complex tachycardia improved with intravenous fat emulsion.
AB  - Diphenhydramine toxicity manifests with signs of anticholinergic toxicity;
      therapy is generally supportive. In rare cases, patients can also present with a
      wide complex tachycardia due to sodium channel blockade. Treatment involves
      sodium bicarbonate. Lidocaine and hypertonic saline are used for arrhythmias
      refractory to sodium bicarbonate. Although intravenous fat emulsion (IFE) therapy
      is proposed as an adjunctive therapy due to the lipophilicity of diphenhydramine
      (octanol/water partition coefficient of 3.3), successful use of IFE after a
      confirmed sole ingestion of diphenhydramine is not previously reported. We
      present the case of a 30-year-old woman presenting with seizures, a wide complex
      tachycardia, and cardiovascular collapse after an ingestion of diphenhydramine
      refractory to other therapies with rapid improvement after IFE administration. 

PMID- 24096707
TI  - Inhibitory effect of gallic acid on CCl4-mediated liver fibrosis in mice.
AB  - The aim of this study was to investigate the effect of gallic acid (GA) on liver
      fibrosis induced by carbon tetrachloride (CCl4). Male BALB/c mice were randomly
      divided into four groups: normal control group (group A), CCl4-induced liver
      injury control group (group B), and CCl4 induction with GA of low dose (5 mg/kg)
      and high dose (15 mg/kg) treatment group (group C and group D). GA was intra
      gastric given for mice once a day after 2 weeks of CCl4 induction. Animals were
      killed at the eighth week. Degrees of fibrosis and collagen percentage were
      measured. Hyaluronic acid (HA), type IV collagen (cIV), malondialdehyde (MDA),
      alanine aminotransferase (ALT), aspartate aminotransferase (AST), and gamma
      glutamyl transferase (gamma-GT) were determined. Expression of matrix
      metalloproteinases-2 (MMP-2) and tissue inhibitor of matrix metalloproteinases-1
      (TIMP-1) mRNA levels were examined by RT-PCR. Western blotting was carried out to
      evaluate the changes of MMP-2 protein. HE and VG stainings showed GA in a dose
      dependent manner improved significantly the fibrosis condition in CCl4-injured
      mice (P < 0.05 or P < 0.01). Also, the concentrations of HA, cIV, and MDA, as
      well as the serum levels of ALT, AST, and gamma-GT were markedly reduced by GA (P
      < 0.05 or P < 0.01), and decreases in MMP-2, TIMP-1 mRNA, and MMP-2 protein were
      observed as well (P < 0.05 or P < 0.01). GA could exert protective effect on
      liver injury and reduce liver fibrosis induced by CCl4 in mice, which might be
      through the inhibition of hepatic stellate cell activity.

PMID- 24096708
TI  - Human amnion mesenchymal cells negative co-stimulatory molecules PD-L1 expression
      and its capacity of modulating microglial activation of CNS.
AB  - The objective of this study is to investigate the negative immunomodulatory
      capacity of human amniotic mesenchymal cells (AMSCs) and their possible intrinsic
      mechanism, by which we can confirm that they modulate microglial activation of
      central nervous system from multiple perspectives at the molecular level. The
      identification of the immune phenotype of AMSCs and microglial cells was executed
      by immunohistochemical methods and flow cytometry. Meanwhile, the influence and
      mechanism of amniotic mesenchymal cells in vitro on proliferation, cell cycle,
      and cytokine release of activated microglia (MI) would be detected by ELISA, beta
      liquid scintillation counting method, and flow cytometry. Human amnion
      mesenchymal cells highly expressed negative co-stimulatory molecules PD-L1, while
      its ligand PD1 was expressed with high level by activated MI. When adding the PD
      L1mAb to the mixed culture system composed of AMSCs and activated MI, the
      proliferation inhibitory effect and the cycle-blocking effect produced by the
      former on the latter would be partially reversed; at the same time, the impact of
      the latter cytokine secretion would be adjusted. As a conclusion, AMSCs play
      inhibitory effects on microglial activation, proliferation, and immune effects
      partially through the PD-L1-PD1 signaling pathways. 

PMID- 24096709
TI  - Broadband asymmetric waveguiding of light without polarization limitations.
AB  - Optical diodes are fundamental elements for optical computing and information
      processing. Attempts to realize such non-reciprocal propagation of light by
      breaking the time-reversal symmetry include using indirect interband photonic
      transitions, the magneto-optical effect, optical nonlinearity or photonic
      crystals. Alternatively, asymmetric reciprocal transmission of light has been
      proposed in photonic metamaterial structures for either circularly or linearly
      polarized waves. Here we employ the recent concept of gradient index
      metamaterials to demonstrate a waveguide with asymmetric propagation of light,
      independent of polarization. The device blocks both transverse electric and
      magnetic polarized modes in one direction but transmits them in the other for a
      broadband spectrum. Unlike previous works using chiral properties of
      metamaterials, our device is based on the principle of momentum symmetry breaking
      at interfaces with phase discontinuities. Experiments in the microwave region
      verify our findings, which may pave the way to feasible passive optical diodes. 

PMID- 24096710
TI  - Estradiol increases ER-negative breast cancer metastasis in an experimental
      model.
AB  - Breast cancer (BC) is the most common cancer affecting women in the United States
      and metastatic breast cancer is the leading cause of death. The role estradiol
      plays in ER-positive BC is well-documented, but the way it contributes to ER
      negative BC remains unclear. In the present study, we utilized an experimental
      model of BC metastasis into lung by injecting ER-negative murine 4T1 cells into
      mice via the lateral tail vein. A 56 % metastasis occurrence rate following the
      injection of 5 * 10(3) cells was observed, thus this cell number was selected to
      study the potential stimulatory effect of estradiol on ER-negative BC metastasis.
      Female ovariectomized mice were randomized into estradiol and control groups with
      16 mice per group, and estradiol pellets were implanted subcutaneously in the
      estradiol group. Results demonstrated that estradiol accelerated BC metastasis as
      indicated by bioluminescent imaging. In addition, estradiol enhanced metastatic
      tumor colony formation and increased the size of tumor nodules in the lungs,
      which were due, in part, to the increase in proliferative cells in the metastatic
      tumors. In vitro, estradiol increased the motility and invasion of 4T1 cells, and
      the stimulatory effect on cell motility was not blocked by ICI 182, 780,
      confirming that ER was not involved in the process. Results from the present
      study suggest that estradiol plays a role in ER-negative BC metastasis in whole
      animals.

PMID- 24096712
TI  - Ascending aorta diameters measured by echocardiography using both leading edge-to
      leading edge and inner edge-to-inner edge conventions in healthy volunteers.
AB  - AIMS: Reference ranges of ascending aorta diameters (AAoD) for two-dimensional
      echocardiography (2DE) using inner edge (IE) convention are lacking, preventing
      the comparison of AAoD measurements by 2DE with those obtained by other imaging
      modalities. METHODS AND RESULTS: We used harmonic imaging 2DE to prospectively
      study 218 healthy volunteers (56% women, 42 +/- 15 years, 18-80 years).
      Measurements were performed at the level of aortic root (AoR), sinotubular
      junction (STJ), and proximal tubular portion (TAo, 1 cm from the STJ) using both
      leading edge (LE) and IE conventions at end-diastole and end-systole. Feasibility
      of AAoD measurements between end-diastole and end-systole was similar at AoR and
      STJ levels, but it was significantly different at TAo level (82 vs. 96%,
      respectively, P < 0.0001). Ascending aorta diameters indexed to height were
      larger in men than in women (P < 0.0001). After adjusting for the effect of
      gender, only age and body surface area (BSA) were independent predictors of AAoD
      at multivariable analysis. Average end-diastolic AoR, STJ, and TAo diameters
      measured using IE convention were similar between genders (17 +/- 2, 15 +/- 2,
      and 15 +/- 2 mm/m(2), respectively). Corresponding AAoD measured using the LE
      convention were 18 +/- 2, 16 +/- 2, and 17 +/- 4 mm/m(2), respectively. On
      average, the end-systolic AAoD measured using LE were 2 mm larger than those
      performed using IE or at end-diastole. Mean aortic wall thickness was 2.4 +/- 0.8
      mm. CONCLUSION: End-diastolic AAoD measured using IE were significantly smaller
      than those obtained either using LE convention or at end-systole. Gender-specific
      reference values for AAoD indexed for BSA should be used to identify ascending
      aorta pathology.

PMID- 24096711
TI  - Underactivation of the adiponectin-adiponectin receptor 1 axis in clear cell
      renal cell carcinoma: implications for progression.
AB  - Energy-sensing pathways, normally coordinated by 5' AMP-activated protein kinase
      (AMPK), are dysregulated in renal cell carcinoma (RCC). Obesity can accentuate
      the pre-existing pro-tumorigenic metabolic machinery in RCC cells through its
      associated obesogenic hormonal milieu, characterized by lower circulating levels
      of adiponectin. In RCC patients, low adiponectin levels associate clinically with
      more aggressive disease. We investigated the adiponectin signaling pathway in
      RCC, focusing on adiponectin receptor 1 (AdipoR1) and associated activation of
      AMPK. AdipoR1 protein in RCC and normal surrounding renal tissues was determined
      by Western blot analysis and immunohistochemistry. Anti-tumorigenic effects of
      adiponectin in RCC cells in vitro were investigated via VEGF and MMP ELISA and
      invasion assays. Using in vivo models of RCC, the effect of AdipoR1-knockdown
      (shRNA) on tumor latency, growth and dissemination were determined. AdipoR1
      protein was significantly reduced in clear cell RCC specimens. Adiponectin
      treatment inhibited VEGF, MMP-2 and MMP-9 secretion and activity and invasive and
      migratory capacities of RCC cells. AMPKalpha1-knockdown (shRNA) attenuated
      adiponectin's effects. In cells stably expressing AdipoR1-specific shRNA, AMPK
      activation by adiponectin was significantly reduced compared to cells expressing
      control shRNA. In vivo, AdipoR1 knockdown increased the growth, dissemination and
      angiogenesis of RCC. These findings suggest that deficiencies in the entire
      adiponectin hormonal axis (the hormone and its receptor) result in
      underactivation of AMPK leading to increased angiogenic and invasive capacities
      of RCC. The established link between obesity and RCC can therefore be further
      explained by the adiponectin deficiency in obese individuals together with
      reduced AdipoR1 protein in RCC. 

PMID- 24096713
TI  - The safety and efficacy of thalamic deep brain stimulation in essential tremor:
      10 years and beyond.
AB  - BACKGROUND: Deep brain stimulation (DBS) has proven to be a safe and effective
      therapy for refractory essential tremor, but information regarding long-term
      outcomes is lacking. OBJECTIVES: We aimed to assess the long-term safety and
      efficacy of DBS in patients with essential tremor. METHODS: Patients treated with
      DBS for essential tremor for at least 8 years were evaluated in the 'on' and
      'off' state using the Fahn-Tolosa-Marin tremor rating scale, and their medical
      records were reviewed to assess complications related to this therapy. RESULTS:
      We studied 13 patients (7 men): median age at evaluation 79 years (range 47-88),
      median age at electrode implantation 68 years (range 37-78) and mean time since
      electrode implantation 132.54+/-15.3 months (range 114-164). The difference
      between the 'off' and 'on' state on the motor items of the tremor rating scale
      was 41.9% (58.62 vs. 34.08, p<0.001) in the non-blinded and 37.2% (56.07 vs.
      35.23, p<0.001) in the blinded rating. DBS provided a functional improvement of
      31.7% in the 'on' state (15.07 vs. 22.07, p<0.001). A total non-blinded
      improvement in the tremor rating scale of 39% was observed in the 'on' state
      (49.15 vs. 80.69, p<0.001). Dysarthria and disequilibrium were common in patients
      with bilateral stimulation. A DBS-related surgery (electrode revision or internal
      pulse generator exchange) was necessary on average every 47.9 months to continue
      with the DBS therapy. CONCLUSIONS: Thalamic DBS is a safe and effective therapy
      in patients with essential tremor followed for up to 13 years.

PMID- 24096714
TI  - Phytohemagglutinin-induced IL2 mRNA in whole blood can predict bortezomib-induced
      peripheral neuropathy for multiple myeloma patients.
AB  - The proteasome inhibitor bortezomib has revolutionized the treatment of multiple
      myeloma. However, bortezomib-induced peripheral neuropathy (BiPN) is a serious
      complication that compromises clinical outcome. If patients with a risk of
      developing BiPN could be predicted, physicians might prefer weekly, reduced-dose,
      or subcutaneous approaches. To seek biomarkers for BiPN, we conducted a
      multicenter prospective study using a simple and unique system. Multiple myeloma
      patients received twice-weekly or weekly 1.3 mg/m(2) bortezomib intravenously,
      and a 2-ml sample of whole blood was obtained before treatment and 2-3 days and 1
      3 weeks after the first dose. Induction of gene expression was then quantified by
      real-time PCR. Of a total of 64 enrolled patients, 53 patient samples qualified
      for mRNA analysis. The BiPN grade was associated with phytohemagglutinin-induced
      IL2, IFNG and TNFSF2, as well as with lipopolysaccharide-induced IL6 levels. More
      importantly, of the 19 patients showing a ?3-fold increase in phytohemagglutinin
      induced IL2, 14 did not suffer from BiPN (73.7% prediction), whereas of the 34
      patients with a <3-fold increase, 23 experienced BiPN (67.6% prediction).
      Therefore, we concluded that pretreatment of phytohemagglutinin-induced IL2 mRNA
      levels in whole blood serve as a promising biomarker for predicting BiPN, and
      this finding warrants validation in a larger study. 

PMID- 24096715
TI  - User-held personalised information for routine care of people with severe mental
      illness.
AB  - BACKGROUND: It is important to seek cost-effective methods of improving the care
      and outcome of those with serious mental illnesses. User-held records, where the
      person with the illness holds all or some personal information relating to the
      course and care of their illness, are now the norm in some clinical settings.
      Their value for those with severe mental illnesses is unknown. OBJECTIVES: To
      evaluate the effects of personalised, accessible, user-held clinical information
      for people with a severe mental illness (defined as psychotic illnesses). SEARCH
      METHODS: We updated previous searches by searching the Cochrane Schizophrenia
      Group Trials Register in August 2011. This register is compiled by systematic
      searches of major databases, and handsearches of journals and conference
      proceedings. SELECTION CRITERIA: We included all relevant randomised controlled
      trials (RCTs) that:i. have recruited adult participants with a diagnosis of a
      severe mental illness (specifically psychotic illnesses and severe mood disorders
      such as bipolar and depression with psychotic features); andii. compared any
      personalised and accessible clinical information held by the user beyond standard
      care to standard information routinely held such as appointment cards and generic
      information on diagnosis, treatment or services available. DATA COLLECTION AND
      ANALYSIS: Study selection and data extraction were undertaken independently by
      two authors and confirmed and checked by a third. We contacted authors of trials
      for additional and missing data. Where possible, we calculated risk ratios (RR)
      and 95% confidence intervals (CI). We used a random-effects model. We assessed
      risk of bias for included studies and created a 'Summary of findings' table using
      GRADE. MAIN RESULTS: Four RCTs (n = 607) of user-held records versus treatment as
      usual met the inclusion criteria. When the effect of user-held records on
      psychiatric hospital admissions was compared with treatment as usual in four
      studies, the pooled treatment effect showed no significant impact of the
      intervention and was of very low magnitude (n = 597, 4 RCTs, RR 0.99 CI 0.71 to
      1.38, moderate quality evidence). Similarly, there was no significant effect of
      the intervention in three studies which investigated compulsory psychiatric
      hospital admissions (n = 507, 4 RCTs, RR 0.64 CI 0.37 to 1.10, moderate quality
      evidence). Other outcomes including satisfaction and mental state were
      investigated but pooled estimates were not obtainable due to skewed or poorly
      reported data, or only being investigated by one study. Two outcomes (violence
      and death) were not investigated by the included studies. Two important
      randomised studies are ongoing. AUTHORS' CONCLUSIONS: The evidence gap remains
      regarding user-held, personalised, accessible clinical information for people
      with psychotic illnesses for many of the outcomes of interest. However, based on
      moderate quality evidence, this review suggests that there is no effect of the
      intervention on hospital or outpatient appointment use for individuals with
      psychotic disorders. The number of studies is low, however, and further evidence
      is required to ascertain whether these results are mediated by the type of
      intervention, such as involvement of a clinical team or the type of information
      included.

PMID- 24096716
TI  - Associations of cardiac structure with obesity, blood pressure, inflammation, and
      insulin resistance in African-American adolescents.
AB  - To determine if obesity, blood pressure (BP), markers of inflammation, and
      insulin resistance are associated with cardiac structure in African-American
      adolescents, a cross-sectional study was performed on a cohort oversampled for
      high BP and obesity. Measurements included the following: anthropometrics, BP,
      homeostasis model assessment (HOMA) to assess insulin resistance, high
      sensitivity C-reactive protein, and plasma adipokines (adiponectin, interleukin
      6, plasminogen activator inhibitor-1). Echocardiogram measurements were left
      ventricular mass index (LVMI) (g/m(2.7)), LV relative wall thickness (LVRWT),
      left-atrial diameter index [LADI (mm/m)], and LV diastolic time intervals. LADI
      (r (2) = 0.25) was associated with body mass index (BMI) systolic BP (SBP) and
      female sex. LVMI (r (2) = 0.35) variation was associated with BMI SBP, heart
      rate, age, and male sex. LVRWT (r (2) = 0.05) was associated with HOMA. Tissue
      diastolic intervals were not associated with any risk factor. Inflammatory
      markers and adipokines were associated with BMI but were not independently
      associated with any echocardiographic measures. In African-American adolescents,
      BMI and SBP, but not inflammatory markers or adipokines, are important correlates
      of LA size and LVM. 

PMID- 24096717
TI  - Single-center outcome analysis comparing reintervention rates of surgical
      arterioplasty with stenting for branch pulmonary artery stenosis in a pediatric
      population.
AB  - Although catheter-based intervention is generally accepted as the treatment of
      choice for branch pulmonary artery (PA) stenosis, there are no data directly
      comparing both the need for reintervention and time to reintervention in patients
      undergoing transcatheter stenting versus surgical arterioplasty. We compared
      children who underwent surgical branch pulmonary arterioplasty and branch PA
      stent placement between January 2008 and May 2012 at a single tertiary center.
      Need for reintervention and mean time to reintervention were assessed using chi
      square and independent sample Student t test. Thirty-seven patients were included
      (surgery n = 18, stent n = 19). Mean weight at initial intervention was 11.3 +/-
      8.8 kg for surgical and 20.1 +/- 15.5 kg for stent (p = 0.041). Intervention was
      performed on the left PA in 17 patients, the right PA in 12 patients, and both
      PAs in 8 patients. Five patients had undergone previous intervention. On mean
      follow-up of 807 +/- 415 days, 50% (9 of 18) of the surgery cohort and 5.3% (1 of
      19) of the stent cohort required reintervention (p = 0.002). In all but one case
      reintervention was catheter-based. Mean time to reintervention for the surgery
      cohort was 272 +/- 162 days and for the single stent cohort it was 150 days. When
      comparable age and weight groups were analyzed, reintervention was still more
      common in the surgery cohort (p = 0.007). Children undergoing surgical branch
      pulmonary arterioplasty are more likely to require reintervention than those
      undergoing stent placement.

PMID- 24096718
TI  - Stenting of the right ventricular outflow tract in the high-risk infant with
      cyanotic teratology of Fallot.
AB  - Neonatal tetralogy of Fallot (TOF) repair carries an increased risk of low
      birthweight or premature infants. Studies are investigating stents in the right
      ventricular outflow tract (RVOT) as an alternative to aortopulmonary shunts. The
      authors review their institutional experience with RVOT stenting in the high-risk
      infant with TOF. Data on sequential patients who received RVOT stents were
      reviewed, with collection of their surgical, echocardiographic, and
      catheterization data. Size-matched control subjects were identified and outcomes
      compared. Six infants went to the catheterization lab for RVOT stenting from 2008
      to 2010. Five of these patients had placement of an RVOT stent after balloon
      dilation. The median saturations were 71% on 48% fraction of inspired oxygen
      (FiO2), with improvement to 94% (p < 0.001) on 39% FiO2 24 h after stent
      placement. As shown by echocardiography, the diameter of the median right
      pulmonary artery (RPA) was 2.6 mm (z-score, -3.3), and the diameter of the left
      pulmonary artery (LPA) was 2.0 mm (z-score, -4.5). Repeat echocardiography before
      surgery showed a statistically significant increase in RPA and LPA size as well
      as a modified McGoon ratio (p < 0.05). Four of the five patients subsequently
      underwent TOF repair. No stent fractures occurred. One patient had repair 10 days
      after stent placement secondary to stent malposition and tricuspid valve injury.
      The authors' experience with stents in the RVOT of TOF patients has yielded good
      results, with significant improvement in oxygen saturations. Patients had
      successful elective surgical repair and stent removal without longer
      cardiopulmonary bypass times or recognizable complications compared with shunted
      patients.

PMID- 24096719
TI  - Single coronary artery anomaly: classification and evaluation using multidetector
      computed tomography and magnetic resonance angiography.
AB  - The aim of this study was to use multidetector computed tomography (MDCT) and
      magnetic resonance (MRA) angiography to illustrate the classification and
      clinical characteristics of single coronary artery anomaly (SCAA). Retrospective
      evaluation of 22 adult and pediatric patients with SCAA by way of a medical
      archiving system was performed between June 2001 and August 2012. Imaging
      modalities used for coronary artery evaluation included MRA and MDCT angiography.
      Of the 22 patients, the majority (n = 8; 36%) showed an interarterial course, the
      subtype having the worst prognosis. The retroaortic course (n = 3; 14%) and
      course anterior to the pulmonary trunk (n = 3; 14%) were the next most frequent
      patterns. Additional types (n = 8; 36%) included the following: L-I, R-III,
      septal, and combined. Four patients (18%) showed atherosclerotic involvement.
      SCAA anomaly was diagnosed as an incidental finding in the majority of patients
      evaluated initially for cardiovascular diseases (n = 19; 86%). Two patients (9%)
      required surgical interventions solely for their anomaly. Nine patients (41%)
      were found to have coexisting congenital heart disease. Although conventional
      catheter angiography is responsible for the current classification of SCAA,
      advanced imaging modalities are useful in the evaluation of morphological and
      clinical characteristics of single coronary arteries.

PMID- 24096720
TI  - Great vessel root and artery dimensions in transposition of the great arteries
      repaired with atrial switch operation.
AB  - To describe great-vessel dimensions in patients with D-loop transposition of the
      great arteries (TGA) who have undergone atrial switch operation (ATSO). Patients
      who have undergone arterial switch operation for TGA have a high incidence of
      dilation of the neoaortic root. The incidence and degree of great artery dilation
      in patients who have undergone ATSO for TGA has not previously been described. A
      retrospective database review identified patients with TGA and intact ventricular
      septum who underwent ATSO at <1 year of age with cardiac magnetic resonance (CMR)
      within the previous 5 years (n = 39). A control group of patients referred for
      CMR with normal findings was identified for comparison (n = 40). Measurements of
      the annulus, root, sinotubular junction, and great vessels were performed, and
      interobserver/intraobserver variability was assessed. Median age of subjects at
      ATSO was 3 months (range 1-12) with median age at CMR of 29 years (range 18-40).
      For aortic measurements, mean z scores (+/- SDs) for patients relative to body
      surface area (BSA)-adjusted normal controls were as follows: annulus 1.41 (0.80),
      root 2.04 (1.48), sinotubular junction 2.16 (1.26), and great vessel 1.86 (1.53).
      For pulmonary measurements, similar values were as follows: annulus 1.82 (1.42),
      root 3.25 (2.01), sinotubular junction 2.47 (1.79), and great vessel 3.96 (3.08).
      In all cases, the p value was <0.001, and no confidence interval included the
      value 0. Adult patients with TGA repaired with ATSO in infancy have a greater
      incidence of dilation of both great vessels, particularly the pulmonary artery.
      These results may indicate abnormalities in the vascular structure of both great
      arteries in TGA that may predispose to progressive arterial dilation.

PMID- 24096721
TI  - Fertility, pregnancy outcomes and deliveries following myomectomy: experience of
      a French Caribbean University Hospital.
AB  - BACKGROUND: Myoma is the most common benign tumor in women of childbearing age,
      with a high frequency in Afro-Caribbean than in other women. Depending on their
      number, size and location, myomas are suspected to be a cause of infertility.
      Conservative treatment by myomectomy is possible for symptomatic patients wishing
      to preserve their fertility. PURPOSE: The aim of this study was to evaluate the
      fertility of patients undergoing myomectomy in the University Hospital of Pointe
      a-Pitre, Guadeloupe. METHODS: We conducted a retrospective study including all
      patients under age 42 who had conservative surgery from January 1st, 2005 to
      December 31st, 2009. The main judgment criteria were the occurrence of
      postoperative pregnancy and its outcome. RESULTS: Of 297 operated patients, 220
      were interviewed by phone (74.1%), 124 (56.3%) had tried to obtain a pregnancy
      and 54 patients (43.5%) had 66 pregnancies (59.1% being live births and 25.8%
      miscarriages). For fertility after surgery, univariate analysis identified the
      number (more than 6, P = 0.0027) and an intramural location (P = 0.027) of myomas
      as negative factors and multivariate analysis identified age (over 35 years, RR =
      2.45) and the association of other causes of infertility (RR = 2.21) as negative
      factors for pregnancy. CONCLUSION: The modest conception rate (43.5%) after
      myomectomy among those women trying to obtain a pregnancy may be linked to the
      specificities of our population, and in particular its relatively high age and
      the frequent association of multiple causes of infertility.

PMID- 24096722
TI  - Cervical cancer screening: the big step from morphology to molecular biology.

PMID- 24096723
TI  - The influence of community and individual health literacy on self-reported health
      status.
AB  - BACKGROUND: Individual health literacy is an established predictor of individual
      health outcomes. Community-level health literacy may also impact individual
      health, yet limited research has simultaneously considered the influence of
      individual and community health literacy on individual health. OBJECTIVE: The
      study goal was to determine if community health literacy had an independent
      relationship with individual self-reported health beyond individual health
      literacy. DESIGN: We used data from the 2008 and 2010 Hawai'i Health Survey, a
      representative statewide telephone survey. Multilevel models predicted individual
      self-reported health by both individual and community health literacy,
      controlling for relevant individual-level (education, race/ethnicity, gender,
      poverty, insurance status, age, and marital status) and community-level variables
      (community poverty and community education). PARTICIPANTS: The sample included
      11,779 individuals within 37 communities. MAIN MEASURES: Individual health
      literacy was defined by validated self-reported measurement. Communities were
      defined by zip code combinations. Community health literacy was defined as the
      percentage of individuals within a community reporting low health literacy.
      Census data by ZIP Code Tabulation Areas provided community-level variables. KEY
      RESULTS: In descriptive results, 18.2 % self-reported low health literacy, and
      14.7 % reported self-reported poor health. Community-level low health literacy
      ranged from 5.37 % to 35.99 %. In final, multilevel models, both individual (OR:
      2.00; 95 % CI: 1.63-2.44) and community low health literacy (OR: 1.02; 95 % CI:
      1.00-1.03) were significantly positively associated with self-reported poor
      health status. Each percentage increase of average low health literacy within a
      community was associated with an approximately 2 % increase in poor self-reported
      health for individuals in that community. Also associated with poorer health were
      lower educational attainment, older age, poverty, and non-White race.
      CONCLUSIONS: Both individual and community health literacy are significant,
      distinct correlates of individual general health status. Primary care providers
      and facilities should consider and address health literacy at both community and
      individual levels.

PMID- 24096724
TI  - Connecting connectomes.

PMID- 24096725
TI  - A material combination principle for highly efficient polymer solar cells
      investigated by mesoscopic phase heterogeneity.
AB  - Organic solar cells have become a promising energy conversion candidate because
      of their unique advantages. Novel fullerene derivatives, as a common acceptor,
      can increase power conversion efficiency (PCE) by increasing the open-circuit
      voltage. As a representative acceptor, Indene-C60 bisadduct (ICBA) can reach high
      efficiency with poly(3-hexylthiophene) (P3HT). On the other hand, the novel
      synthesized polymers mainly aimed to broaden the optical absorption range have
      steadily promoted efficiency to higher than 9%. However, it is challenging to
      obtain the desired result by simply combining ICBA with other high-efficiency
      donors. Thus, P3HT or a high-efficiency polymer PBDTTT-C-T (copolymer of thienyl
      substituted BDT with substituted TT) is used as donor and PCBM or ICBA as
      acceptor in this article to clarify the mechanism behind these materials. The
      optical and photovoltaic properties of the materials are studied for pair-wise
      combination. Among these four material groups, the highest PCE of 6.2% is
      obtained for the PBDTTT-C-T/PCBM combination while the lowest PCE of 3.5% is
      obtained for the PBDTTT-C-T/ICBA combination. The impact of the mesoscopic
      heterogeneity on the local mesoscopic photoelectric properties is identified by
      photo-conductive AFM (pc-AFM), and the consistence between the mesoscopic
      properties and the macroscopic device performances is also observed. Based on
      these results, an interface combined model is proposed based on the mesoscopic
      phase heterogeneity. This study provides a new view on the rational selection of
      photovoltaic materials, where, aside from the traditional energy level and
      absorption spectrum matching, the matching of mesoscopic heterogeneity must also
      be considered. 

PMID- 24096726
TI  - Proton-bound dimers of 1-methylcytosine and its derivatives: vibrational and NMR
      spectroscopy.
AB  - Vibrational spectroscopy and NMR demonstrate that the proton-bound dimer of 1
      methylcytosine, 1, has an unsymmetrical structure at room temperature. In the gas
      phase, investigation of isolated homodimer 1 reveals five fundamental NH
      vibrations by IR Multiple Photon Dissociation (IRMPD) action spectroscopy. The
      NH...N stretching vibration between the two ring nitrogens exhibits a frequency
      of 1570 cm(-1), as confirmed by examination of the proton-bound homodimers of 5
      fluoro-1-methycytosine, 2, and of 1,5-dimethylcytosine, 3, which display
      absorptions in the same region that disappear upon deuterium substitution. (13)C,
      and (15)N NMR of the solid iodide salt of 1 confirm the nonequivalence of the two
      rings in the anhydrous proton-bound homodimer at room temperature. IRMPD spectra
      of the three possible heterodimers also show NH...N stretches in the same domain,
      and at least one of the heterodimers, the proton-bound dimer of 1,5
      dimethylcytosine with 1-methylcytosine, exhibits two bands suggestive of the
      presence of two tautomers close in energy.

PMID- 24096727
TI  - Traumatic tricuspid valve detachment from annulus diagnosed on 3-D
      transesophageal echocardiography.

PMID- 24096728
TI  - Sawtooth electrocardiographic pattern with blocked cavotricuspid isthmus.

PMID- 24096729
TI  - Melanoma on tattoos: two Finnish cases.

PMID- 24096730
TI  - Effectiveness of a multifactorial handwashing program to reduce school
      absenteeism due to acute gastroenteritis.
AB  - BACKGROUND: Acute gastroenteritis (AGE) is one of the most common diseases among
      children and an important cause of school absenteeism. The aim of this study was
      to assess the effectiveness of a handwashing program using hand sanitizers for
      the prevention of school absenteeism due to AGE. METHODS: A randomized,
      controlled and open study of a sample of 1341 children between 4 and 12 years of
      age, attending 5 state schools in Almeria (Spain), with an 8-month follow up
      (academic year). The experimental group (EG) washed their hands with soap and
      water, complementing this with the use of a hand sanitizer, and the control group
      (CG) followed the usual handwashing procedure. Absenteeism rates due GI were
      compared between the 2 groups through the multivariate Poisson regression
      analysis. Percent days absent in both groups were compared with a Z-test.
      RESULTS: 446 cases of school absenteeism due to AGE were registered. The school
      children from the EG had a 36% lower risk of absenteeism due to AGE (IRR: 0.64,
      95% confidence interval: 0.52-0.78) and a decrease in absenteeism of 0.13
      episodes/child/academic year (0.27 of EG vs 0.40 CG/episodes/child/academic year,
      P < 0.001). Pupils missed 725 school days due to AGE and absent days was
      significantly lower in the EG (EG: 0.31%, 95% confidence interval: 0.28-0.35 vs.
      CG: 0.44%, 95% confidence interval: 0.40-0.48, P < 0.001). CONCLUSIONS: The use
      of hand sanitizer as a complement to handwashing with soap is an efficient
      measure to reduce absent days and the number of school absenteeism cases due to
      AGE.

PMID- 24096731
TI  - A prospective study of intrafamilial oropharyngeal transmission of Kingella
      kingae.
AB  - To evaluate the intrafamilial oropharyngeal transmission of Kingella kingae, we
      conducted a prospective study among pairs of siblings. We found that 55% of
      children who suffered from osteoarticular infections due to K. kingae, and 40% of
      asymptomatic carriers of K. kingae had siblings with positive oropharyngeal
      carriage. 

PMID- 24096732
TI  - Identification of QTLs conferring resistance to downy mildew in legacy cultivars
      of lettuce.
AB  - Many cultivars of lettuce (Lactuca sativa L.), the most popular leafy vegetable,
      are susceptible to downy mildew disease caused by Bremia lactucae. Cultivars
      Iceberg and Grand Rapids that were released in the 18th and 19th centuries,
      respectively, have high levels of quantitative resistance to downy mildew. We
      developed a population of recombinant inbred lines (RILs) originating from a
      cross between these two legacy cultivars, constructed a linkage map, and
      identified two QTLs for resistance on linkage groups 2 (qDM2.1) and 5 (qDM5.1)
      that determined resistance under field conditions in California and the
      Netherlands. The same QTLs determined delayed sporulation at the seedling stage
      in laboratory experiments. Alleles conferring elevated resistance at both QTLs
      originate from cultivar Iceberg. An additional QTL on linkage group 9 (qDM9.1)
      was detected through simultaneous analysis of all experiments with mixed-model
      approach. Alleles for elevated resistance at this locus originate from cultivar
      Grand Rapids.

PMID- 24096733
TI  - TAB2, an important upstream adaptor of interleukin-1 signaling pathway, is
      subject to SUMOylation.
AB  - SUMOylation has been considered as an important mechanism to regulate multiple
      cellular processes, including inflammation. TAB2 (TAK1-binding protein 2) is an
      upstream adaptor protein in the IL-1 signaling pathway. Covalent modifications of
      TAB2 have not been well studied. In this study, we demonstrated that TAB2 could
      be modified by SUMO. Using Ubc9 (SUMO-conjugating enzyme) fusion and mutation
      analysis, we identified evolutionarily conserved lysine 329 as the major
      SUMOylation site of TAB2. PIAS3, a SUMO E3 ligase, preferentially interacted with
      and promoted its SUMOylation. Interestingly, block of SUMOylation by mutation of
      lysine 329 enhanced the activity of TAB2, as reflected by AP-1 luciferase
      reporter assays. Taken together, these results suggest that SUMOylation may serve
      as a novel mechanism for the regulation of TAB2.

PMID- 24096734
TI  - Prevention of RhoA activation and cofilin-mediated actin polymerization mediates
      the antihypertrophic effect of adenosine receptor agonists in angiotensin II- and
      endothelin-1-treated cardiomyocytes.
AB  - Adenosine receptor activation has been shown to be associated with diminution of
      cardiac hypertrophy and it has been suggested that endogenously produced
      adenosine may serve to blunt pro-hypertrophic processes. In the present study, we
      determined the effects of two pro-hypertrophic stimuli, angiotensin II (Ang II,
      100 nM) and endothelin-1 (ET-1, 10 nM) on Ras homolog gene family, member A
      (RhoA)/Rho-associated, coiled-coil containing protein kinase (ROCK) activation in
      cultured neonatal rat ventricular myocytes and whether the latter serves as a
      target for the anti-hypertrophic effect of adenosine receptor activation. Both
      hypertrophic stimuli potently increased RhoA activity with peak activation
      occurring 15-30 min following agonist addition. These effects were associated
      with significantly increased phosphorylation (inactivation) of cofilin, a
      downstream mediator of RhoA, an increase in actin polymerization, and increased
      activation and nuclear import of p38 mitogen activated protein kinase. The
      ability of both Ang II and ET-1 to activate the RhoA pathway was completely
      prevented by the adenosine A1 receptor agonist N (6)-cyclopentyladenosine, the
      A2a receptor agonist 2-p-(2-carboxyethyl)-phenethylamino-5'-N
      ethylcarboxamidoadenosine, the A3 receptor agonist N (6)-(3-iodobenzyl)adenosine
      5'-methyluronamide as well as the nonspecific adenosine analog 2-chloro
      adenosine. All effects of specific receptor agonists were prevented by their
      respective receptor antagonists. Moreover, all adenosine agonists prevented
      either Ang II- or ET-1-induced hypertrophy, a property shared by the RhoA
      inhibitor Clostridium botulinum C3 exoenzyme, the ROCK inhibitor Y-27632 or the
      actin depolymerizing agent latrunculin B. Our study therefore demonstrates that
      both Ang II and ET-1 can activate the RhoA pathway and that prevention of the
      hypertrophic response to both agonists by adenosine receptor activation is
      mediated by prevention of RhoA stimulation and actin polymerization.

PMID- 24096735
TI  - Influence of monoclonal anti-Lewis b, anti-H type 1, and anti-sialyl Lewis x
      antibodies on binding of Helicobacter pylori to MUC1 mucin.
AB  - To assess the influence of monoclonal anti-Lewis b, anti-H type 1, and anti
      sialyl Lewis x addition on interactions of sugar structures of MUC1 mucin with
      Helicobacter pylori. The investigations were carried out on gastric juices of 11
      patients and 12 H. pylori strains. The levels of Lewis b and sialyl Lewis x
      antigens on MUC1 were assessed by sandwich ELISA tests. Anti-Lewis b, anti-H type
      1 or anti-sialyl Lewis x monoclonal antibodies were added to MUC1 to determine
      whether the adhesion activities of H. pylori isolates to examined mucin would be
      affected. Binding of bacteria to MUC1 was assessed by ELISA test. Clear
      inhibitory effect of examined antibodies was revealed in 6 of 12 examined H.
      pylori isolates independently on babA2 status. In the rest of strains this effect
      was negligible. We confirmed participation of Lewis b, H type 1 and also sialyl
      Lewis x of MUC1 mucin in interactions with H. pylori independently on babA
      genopositivity. Not full inhibition and a lack of this effect in some strains
      suggest an existence of other mechanisms of H. pylori adherence to mucin.

PMID- 24096736
TI  - Metformin reverses multidrug resistance and epithelial-mesenchymal transition
      (EMT) via activating AMP-activated protein kinase (AMPK) in human breast cancer
      cells.
AB  - Breast cancer is the most frequently diagnosed tumor type and the primary leading
      cause of cancer deaths in women worldwide and multidrug resistance is the major
      obstacle for breast cancer treatment improvement. Emerging evidence suggests that
      metformin, the most widely used antidiabetic drug, resensitizes and cooperates
      with some anticancer drugs to exert anticancer effect. However, there are no data
      regarding the reversal effect of metformin on chemoresistance in breast cancer.
      In the present study, we investigated the resistance reversal effect of metformin
      on acquired multidrug-resistant breast cancer cells MCF-7/5-Fu derived from MCF-7
      breast cancer cells and innate multidrug-resistant MDA-MB-231 breast cancer
      cells, and we found that metformin resensitized MCF7/5-FU and MDA-MB-231 to 5
      fluorouracil (5-FU), adriamycin, and paclitaxel. We also observed that metformin
      reversed epithelial-mesenchymal transition (EMT) phenotype and decreased the
      invasive capacity of MCF7/5-FU and MDA-MB-231 cells. However, there were no
      significant changes upon metformin-treated MCF7 cells. Moreover, we found
      metformin treatment activated AMPK signal pathway in MCF7/5-FU and MDA-MB-231
      cells and compound C, the AMPK inhibitor, could partly abolish the
      resensitization and EMT reversal effect of metformin. To the best of our
      knowledge, we are the first to report that metformin can resensitize multidrug
      resistant breast cancer cells due to activating AMPK signal pathway. Our study
      will help elucidate the mechanism of chemoresistance and establish new strategies
      of chemotherapy for human breast cancer. 

PMID- 24096737
TI  - Primary 4T1 tumor resection provides critical "window of opportunity" for
      immunotherapy.
AB  - It is believed that primary tumor resection modulates host-tumor immune
      interaction, but this has not been characterized in a stringent breast cancer
      tumor model. This report, using the 4T1 murine mammary tumor model, characterizes
      for the first time the dynamic longitudinal changes in immunosuppressive and
      effector components of the immune system after resection of an established
      orthotopic primary tumor with a defined natural history of developing lung
      metastases. More specifically, we analyzed changes of absolute numbers and
      frequencies of MDSC, regulatory T cells (Treg), as well as activated CD4 and CD8
      positive T cells in spleens and, in some studies, lungs of 4T1 tumor-bearing mice
      and mice after primary tumor resection. Importantly, using mathematical analyses
      we established that primary resection of an orthotopic tumor had created a
      "window of opportunity" with decreased tumor-associated immune suppression that
      existed for approximately 10 days. Although tumor resection did slightly prolong
      survival, it did not affect the ultimate development of metastatic disease since
      animals with resected tumors or intact primary tumors eventually died by day 47
      and 43, respectively. This window of opportunity likely occurs in humans
      providing a rationale and parameters for integration and testing of
      immunotherapeutic strategies in this critical "window of opportunity" to combat
      the development of metastatic disease.

PMID- 24096738
TI  - Plant functional traits reveal the relative contribution of habitat and food
      preferences to the diet of grasshoppers.
AB  - Food preferences and food availability are two major determinants of the diet of
      generalist herbivores and of their spatial distribution. How do these factors
      interact and eventually lead to diet differentiation in co-occurring herbivores?
      We quantified the diet of four grasshopper species co-occurring in subalpine
      grasslands using DNA barcoding of the plants contained in the faeces of
      individuals sampled in the field. The food preferences of each grasshopper
      species were assessed by a choice (cafeteria) experiment from among 24 plant
      species common in five grassland plots, in which the four grasshoppers were
      collected, while the habitat was described by the relative abundance of plant
      species in the grassland plots. Plant species were characterised by their leaf
      economics spectrum (LES), quantifying their nutrient vs. structural tissue
      content. The grasshoppers' diet, described by the mean LES of the plants eaten,
      could be explained by their plant preferences but not by the available plants in
      their habitat. The diet differed significantly across four grasshopper species
      pairs out of six, which validates food preferences assessed in standardised
      conditions as indicators for diet partitioning in nature. In contrast, variation
      of the functional diversity (FD) for LES in the diet was mostly correlated to the
      FD of the available plants in the habitat, suggesting that diet mixing depends on
      the environment and is not an intrinsic property of the grasshopper species. This
      study sheds light on the mechanisms determining the feeding niche of herbivores,
      showing that food preferences influence niche position whereas habitat diversity
      affects niche breadth. 

PMID- 24096739
TI  - Genetic variation in plant volatile emission does not result in differential
      attraction of natural enemies in the field.
AB  - Volatile organic chemical (VOC) emission by plants may serve as an adaptive plant
      defense by attracting the natural enemies of herbivores. For plant VOC emission
      to evolve as an adaptive defense, plants must show genetic variability for the
      trait. To date, such variability has been investigated primarily in agricultural
      systems, yet relatively little is known about genetic variation in VOCs emitted
      by natural populations of native plants. Here, we investigate intraspecific
      variation in constitutive and herbivore-induced plant VOC emission using the
      native common milkweed plant (Asclepias syriaca) and its monarch caterpillar
      herbivore (Danaus plexippus) in complementary field and common garden greenhouse
      experiments. In addition, we used a common garden field experiment to gauge
      natural enemy attraction to milkweed VOCs induced by monarch damage. We found
      evidence of genetic variation in the total constitutive and induced
      concentrations of VOCs and the composition of VOC blends emitted by milkweed
      plants. However, all milkweed genotypes responded similarly to induction by
      monarchs in terms of their relative change in VOC concentration and blend.
      Natural enemies attacked decoy caterpillars more frequently on damaged than on
      undamaged milkweed, and natural enemy visitation was associated with higher total
      VOC concentrations and with VOC blend. Thus, we present evidence that induced
      VOCs emitted by milkweed may function as a defense against herbivores. However,
      plant genotypes were equally attractive to natural enemies. Although milkweed
      genotypes diverge phenotypically in their VOC concentrations and blends, they
      converge into similar phenotypes with regard to magnitude of induction and enemy
      attraction. 

PMID- 24096740
TI  - Tree diversity promotes functional dissimilarity and maintains functional
      richness despite species loss in predator assemblages.
AB  - The effects of species loss on ecosystems depend on the community's functional
      diversity (FD). However, how FD responds to environmental changes is poorly
      understood. This applies particularly to higher trophic levels, which regulate
      many ecosystem processes and are strongly affected by human-induced environmental
      changes. We analyzed how functional richness (FRic), evenness (FEve), and
      divergence (FDiv) of important generalist predators-epigeic spiders-are affected
      by changes in woody plant species richness, plant phylogenetic diversity, and
      stand age in highly diverse subtropical forests in China. FEve and FDiv of
      spiders increased with plant richness and stand age. FRic remained on a constant
      level despite decreasing spider species richness with increasing plant species
      richness. Plant phylogenetic diversity had no consistent effect on spider FD. The
      results contrast with the negative effect of diversity on spider species richness
      and suggest that functional redundancy among spiders decreased with increasing
      plant richness through non-random species loss. Moreover, increasing functional
      dissimilarity within spider assemblages with increasing plant richness indicates
      that the abundance distribution of predators in functional trait space affects
      ecological functions independent of predator species richness or the available
      trait space. While plant diversity is generally hypothesized to positively affect
      predators, our results only support this hypothesis for FD-and here particularly
      for trait distributions within the overall functional trait space-and not for
      patterns in species richness. Understanding the way predator assemblages affect
      ecosystem functions in such highly diverse, natural ecosystems thus requires
      explicit consideration of FD and its relationship with species richness. 

PMID- 24096741
TI  - Long-term dissemination of acquired AmpC beta-lactamases among Klebsiella spp.
      and Escherichia coli in Portuguese clinical settings.
AB  - We investigated the occurrence, diversity and molecular epidemiology of genes
      coding for acquired AmpC beta-lactamases (qAmpC) among clinical isolates of
      Enterobacteriaceae lacking inducible chromosomal AmpCs in Portugal. A total of
      675 isolates non-susceptible to broad-spectrum cephalosporins obtained from four
      hospitals and three community laboratories during a 7-year period (2002-2008)
      were analysed. The presence of genes coding for qAmpC was investigated by
      phenotypic criteria, polymerase chain reaction (PCR) and sequencing. Bacterial
      identification, antibiotic susceptibility testing, conjugation assays and clonal
      analysis were performed by standard procedures. The presence of bla(qAmpC) genes
      was detected in 50 % (50/100; 41 Klebsiella pneumoniae, 5 Escherichia coli, 4
      Klebsiella oxytoca) of the presumptive qAmpC producers. DHA-1, detected in those
      species, was the most prevalent qAmpC (94 %, 47/50), being identified since 2003
      and throughout the studied period in different institutions. Despite the high
      clonal diversity observed, three DHA-1-producing Klebsiella spp. clones were more
      frequently identified. CMY-2 (6 %, 3/50) was observed in B1-E. coli clones.
      Conjugative transfer was only observed in one (2 %) CMY-2-producing isolate. Most
      qAmpC producers (94 %, 47/50) co-expressed SHV-type and/or OXA-1 or CTX-M-32
      extended-spectrum beta-lactamases (ESBLs). To the authors' knowledge, this is the
      first description of the molecular epidemiology and the long-term dissemination
      of qAmpC-producing Enterobacteriaceae in Portuguese clinical settings,
      highlighting an evolution towards a more complex epidemiological situation
      regarding cephalosporin resistance in Portugal.

PMID- 24096742
TI  - Smad6 inhibits non-canonical TGF-beta1 signalling by recruiting the
      deubiquitinase A20 to TRAF6.
AB  - Transforming growth factor (TGF)-beta, a pivotal cytokine involved in a variety
      of cellular functions, transmits signals through Smad-dependent canonical and
      Smad-independent noncanonical pathways. In contrast to the canonical TGF-beta
      pathway, it is unknown how noncanonical TGF-beta pathways are negatively
      regulated. Here we demonstrate that the inhibitory Smad Smad6, but not Smad7,
      negatively regulates TGF-beta1-induced activation of the TRAF6-TAK1-p38 MAPK/JNK
      pathway, a noncanonical TGF-beta pathway. TGF-beta1-induced Smad6 abolishes K63
      linked polyubiquitination of TRAF6 by recruiting the A20 deubiquitinating enzyme
      in AML-12 mouse liver cells and primary hepatocytes. In addition, the knockdown
      of Smad6 or A20 in an animal model or cell culture system maintains TAK1 and p38
      MAPK/JNK phosphorylation and increases apoptosis, emphasizing the crucial role of
      the Smad6-A20 axis in negative regulation of the TGF-beta1-TRAF6-TAK1-p38
      MAPK/JNK pathway. Therefore, our findings provide insight into the molecular
      mechanisms underlying negative regulation of noncanonical TGF-beta pathways.

PMID- 24096743
TI  - Chinese herbal medicine for diabetic peripheral neuropathy.
AB  - BACKGROUND: Chinese herbal medicine is frequently used for treating diabetic
      peripheral neuropathy in China. Many controlled trials have been undertaken to
      investigate its efficacy.This is an update of a Cochrane review that was first
      published in the year 2011. OBJECTIVES: To assess the beneficial effects and
      harms of Chinese herbal medicine for people with diabetic peripheral neuropathy.
      SEARCH METHODS: On 14 May 2012, we searched the Cochrane Neuromuscular Disease
      Group Specialized Register CENTRAL (2012, Issue 4 in The Cochrane Library),
      MEDLINE (January 1966 to May 2012), EMBASE (January 1980 to May 2012), AMED
      (January 1985 to May 2012) and in October 2012, the Chinese Biomedical Database
      (CBM) (1979 to October 2012), Chinese National Knowledge Infrastructure Database
      (CNKI) (1979 to October 2012), and VIP Chinese Science and Technique Journals
      Database (1989 to October 2012). We searched for unpublished literature in the
      Chinese Conference Papers Database, and Chinese Dissertation Database (from
      inception to October 2012). There were no language or publication restrictions.
      SELECTION CRITERIA: We included randomised controlled trials of Chinese herbal
      medicine (with a minimum of four weeks treatment duration) for people with
      diabetic peripheral neuropathy compared with placebo, no intervention, or
      conventional interventions. Trials of herbal medicine plus a conventional drug
      versus the drug alone were also included. DATA COLLECTION AND ANALYSIS: Two
      authors independently extracted data and evaluated trial quality. We contacted
      study authors for additional information. MAIN RESULTS: Forty-nine randomised
      trials involving 3639 participants were included. All trials were conducted and
      published in China. Thirty-eight different herbal medicines were tested in these
      trials, including four single herbs (extracts from a single herb), eight
      traditional Chinese patent medicines, and 26 self concocted Chinese herbal
      compound prescriptions. The trials reported on global symptom improvement
      (including improvement in numbness or pain) and changes in nerve conduction
      velocity. The positive results described from the 49 studies of low quality are
      of questionable significance. There was inadequate reporting on adverse events in
      the included trials. Eighteen trials found no adverse events. Two trials reported
      adverse events: adverse events occurred in the control group in one trial, and in
      the other it was unclear in which group the adverse events occurred. 29 trials
      did not mention whether they monitored adverse events. Conclusions cannot be
      drawn from this review about the safety of herbal medicines, due to inadequate
      reporting. Most of the trials were of very low methodological quality and
      therefore the interpretation of any positive findings for the efficacy of the
      included Chinese herbal medicines for treating diabetic peripheral neuropathy
      should be made with caution. AUTHORS' CONCLUSIONS: Based on this systematic
      review, there is no evidence to support the objective effectiveness and safety of
      Chinese herbal medicines for diabetic peripheral neuropathy. No well-designed,
      randomised, placebo controlled trial with objective outcome measures has been
      conducted.

PMID- 24096744
TI  - Breed-specific legislation is not the answer.

PMID- 24096745
TI  - Novel perioperative models make a difference in outcomes of elderly surgical
      patients.

PMID- 24096746
TI  - Tumor regression after neoadjuvant chemotherapy in gastric carcinoma: are there
      really so few responders?

PMID- 24096747
TI  - Prehospital intravenous fluid administration is associated with higher mortality
      in trauma patients: a National Trauma Data Bank analysis.

PMID- 24096748
TI  - A title that may not be appropriate.

PMID- 24096749
TI  - Reply to letter: "A title that may not be appropriate".

PMID- 24096750
TI  - Surgery for small and asymptomatic branch-duct IPMNs.

PMID- 24096751
TI  - Improving ATLS performance in simulated pediatric trauma resuscitation using a
      checklist.
AB  - OBJECTIVE: To develop a checklist for use during pediatric trauma resuscitation
      and test its effectiveness during simulated resuscitations. BACKGROUND:
      Checklists have been used to support a wide range of complex medical activities
      and have effectively reduced errors and improved outcomes in different medical
      settings. Checklists have not been evaluated in the domain of trauma
      resuscitation. METHODS: A focus group of trauma specialists was organized to
      develop a checklist for pediatric trauma resuscitation. This checklist was then
      tested in simulated trauma resuscitations to evaluate its impact on team
      performance. Resuscitations conducted with and without the checklist were
      compared using the Advanced Trauma Life Support (ATLS) performance score,
      designed to measure adherence to ATLS protocol, and surveys of team members'
      subjective workload. RESULTS: The focus group generated a checklist with 56 items
      divided into 5 sections corresponding to different phases of trauma
      resuscitation. In simulation testing, the total ATLS performance score was 4.9
      points higher with a checklist than without (P < 0.001), with most of this
      difference related to improvement in performance of the secondary survey (+3.3
      points, P < 0.001). Overall, workload scores were not affected by the addition of
      the checklist. CONCLUSIONS: Implementing a checklist during simulated pediatric
      trauma resuscitation improves adherence to the ATLS protocol without increasing
      the workload of trauma team members.

PMID- 24096752
TI  - Predictors for anastomotic leak after colon and rectal resection.

PMID- 24096753
TI  - Vitamin B(12) deficiency after gastrectomy for gastric cancer: an analysis of
      clinical patterns and risk factors.
AB  - OBJECTIVE: To identify risk factors for postgastrectomy vitamin B12 deficiency
      and the time course of its development. BACKGROUND: Postgastrectomy vitamin B12
      deficiency worsens the quality of life of gastric cancer survivors, and vitamin
      B12-related neuropathy is irreversible if recognized late. However, the clinical
      pattern of vitamin B12 deficiency development after gastrectomy remains unclear.
      METHODS: We reviewed 645 patients with gastric cancer who underwent distal
      subtotal gastrectomy (DG; n = 469) or total gastrectomy (TG, n = 176) between
      2003 and 2010. Univariate and multivariate analyses were performed to identify
      risk factors for vitamin B12 deficiency and time to deficiency. RESULTS:
      Cumulative vitamin B12 deficiency rates were 100% for TG and 15.7% for DG 4 years
      after surgery (P < 0.001). The median time to vitamin B12 deficiency was 15
      months after TG, whereas the median time was not reached after DG. Preoperative
      vitamin B12 level was the only risk factor for vitamin B12 deficiency after TG,
      whereas both preoperative vitamin B12 level and age were risk factors after DG.
      There was positive linear correlation between preoperative vitamin B12 levels and
      the time to vitamin B12 deficiency after either TG (P < 0.001) or DG (P = 0.017).
      CONCLUSIONS: Vitamin B12 deficiency is an inevitable and rather early metabolic
      sequela after TG. Elderly patients with low preoperative vitamin B12 levels are
      more likely to experience vitamin B12 deficiency after DG. Thus, preoperative
      measurement and regular postoperative monitoring of vitamin B12 levels are
      necessary for early detection and treatment of postgastrectomy vitamin B12
      deficiency.

PMID- 24096754
TI  - Prognostic risk factors of early esophageal adenocarcinomas.
AB  - OBJECTIVE: To define prognostic risk factors in patients with early
      adenocarcinomas of the esophagus (eACEs) who were treated by esophagectomy.
      BACKGROUND: Although endoscopic resection (ER) is more accepted for eACEs limited
      to the mucosa, the reported prevalence of lymph node metastases once the tumor
      infiltrates the submucosa seems to necessitate surgery in these cases. METHODS:
      We analyzed the results of 168 patients who had an esophageal resection because
      of an eACE. On the basis of specimen histologies and clinical follow-up (median,
      64 months), we investigated the influence of lymph node metastases (N+), tumor
      infiltration depth, tumor differentiation (G1-3), and lymphatic or venous
      infiltration (L+ or V+) on overall and tumor-specific survival and recurrence
      rates. RESULTS: The 5-year survival rate was 79%. Lymph node infiltration was the
      only prognostic factor for the overall survival [hazard ratio (HR), 2.856; 1.314
      6.207; P = 0.008], tumor-specific survival (HR, 8.336; 2.734-25.418; P < 0.001),
      and tumor recurrence (HR, 8.031; 3.041-21.206; P < 0.001) that was consistently
      present in all multivariate hazard Cox regression analyses. A total of 47% of the
      patients who had an N+ status developed tumor recurrences compared with 5.2% of
      those who had no lymph node involvement (P = <0.001). We found a significant
      correlation between N+ status and increasing depth of tumor infiltration (P =
      0.004), lymphatic vessel infiltration (P = 0.002), tumor differentiation (G1 + G2
      vs G3; P = 0.014) and vascular infiltration (P = 0.01). CONCLUSIONS: Lymph node
      status is the only independent risk factor for survival and recurrence rates.
      Tumor infiltration depth correlates with the rate of the lymph node metastases,
      but a clear watershed between deep mucosal and submucosal infiltration does not
      exist. As a consequence, careful staging procedures, including diagnostic ER, are
      mandatory to determine which patients can be treated by ER and which require an
      esophagectomy.

PMID- 24096755
TI  - Is there a role for surgery for patients with a complete clinical response after
      chemoradiation for esophageal cancer? An intention-to-treat case-control study.
AB  - OBJECTIVE: To compare the outcomes of a strategy of surveillance versus surgical
      resection in patients with esophageal cancer (EC) experiencing complete clinical
      response (cCR) after chemoradiation (CRT). BACKGROUND: In EC, it remains unclear
      whether a strategy of surveillance or esophagectomy is appropriate after cCR to
      CRT. METHODS: From 1995 to 2009, 222 operable patients had a cCR based on the
      results of a computed tomographic scan, endoscopy with biopsies and, when
      performed, a positron emission tomographic scan. Through an intention-to-treat
      case-control study, 59 patients treated with CRT and surveillance (group Surv)
      were matched 1:2 with 118 patients treated by CRT followed by surgery (group
      Surg), according to age, gender, tumor location and stage, histology, American
      Society of Anesthesiologists score, and nutritional status. RESULTS: The 2 groups
      were comparable according to the matched variables (P > 0.276). In group Surg,
      the postoperative mortality rate was 4.2% with evidence of residual tumor in
      34.6% of specimens. In group Surv, 2 salvage esophagectomies were performed.
      Despite the higher dose of radiotherapy received in group Surv (50 vs 45 Gys, P =
      0.003), median survival was lower (31 vs 83 months, P = 0.001), with disease
      recurrence that was more frequent (50.8% vs 32.7%, P = 0.021), occurred earlier
      (7.8 vs 19.0 months, P = 0.002) and more often locoregional (46.7% vs 16.2%, P =
      0.007) in nature. Surgical resection was independently associated with less
      recurrence [odds ratio = 0.4, 95% confidence interval (CI): 0.2-0.8, P = 0.006]
      and better survival (hazard ratio = 0.5, 95% CI: 0.3-0.8, P = 0.006).
      CONCLUSIONS: Survival of EC patients with a cCR after CRT is better after surgery
      compared to simply surveillance. In patients of low operative risk and operable
      disease, surgery should be considered to improve control of locoregional disease
      and to overcome the inherent limitations of clinical response assessment.

PMID- 24096756
TI  - Differences in circumferential resection margin involvement after
      abdominoperineal excision and low anterior resection no longer significant.
AB  - OBJECTIVE: The aim of this study was to evaluate whether the abdominoperineal
      excision (APE) is associated with an increased risk of circumferential resection
      margin (CRM) involvement after rectal cancer surgery in comparison with low
      anterior resection (LAR). BACKGROUND: The oncologic inferiority of the APE
      technique in comparison with LAR has been widely reported in literature. However,
      because of large evolvement in rectal cancer care, outcomes after APE may have
      improved since then. METHODS: The population-based dataset of the Dutch Surgical
      Colorectal Audit was used selecting 5017 patients with primary rectal cancer
      undergoing surgery in 2010 to 2011. Propensity scores were calculated for the
      likelihood of performing an APE given relevant patient and tumor characteristics,
      and used in the multivariate analysis of CRM involvement. RESULTS: The APE was
      associated with a slight, nonsignificant, increased risk of CRM involvement [odds
      ratio (OR) = 1.33; confidence interval (CI) = 0.93-1.90]. Absolute percentages of
      CRM involvement were 8% and 12% after LAR and APE, respectively.In the subgroup
      analysis, advanced rectal tumors (cT3-4) were associated to a higher risk of CRM
      involvement after APE (OR = 1.61; CI = 1.05-1.90), whereas smaller tumors (cT1-2)
      were not (OR = 0.62; CI = 0.27-1.40). CONCLUSIONS: The results suggest that on a
      national level the APE procedure itself is not a strong predictor anymore for CRM
      involvement after rectal cancer surgery. However, in advanced tumors, results
      after APE are inferior to LAR.

PMID- 24096757
TI  - Geriatric assessment improves prediction of surgical outcomes in older adults
      undergoing pancreaticoduodenectomy: a prospective cohort study.
AB  - OBJECTIVE: To prospectively evaluate the additional value of geriatric assessment
      (GA) for predicting surgical outcomes in a cohort of older patients undergoing a
      pancreaticoduodenectomy (PD) for pancreatic tumors. BACKGROUND: Older patients
      are less often referred for possible PD. Standard preoperative assessments may
      underestimate the likelihood of significant adverse outcomes. The prospective
      utility of validated GA has not been studied in this group. METHODS: PD-eligible
      patients were enrolled in a prospective outcome study. Standard preoperative
      assessments were recorded. Elements of validated GA were also measured, including
      components of Fried's model of frailty, the Vulnerable Elders Survey (VES-13),
      and the Short Physical Performance Battery (SPPB). All postoperative adverse
      events were recorded, systematically reviewed, and graded using the Clavien-Dindo
      system by a surgeon blinded to the GA results. Multivariate regression analyses
      were conducted. RESULTS: Seventy-six older patients underwent a PD. Significant
      unrecognized vulnerability was identified at the baseline: Fried's "exhaustion"
      (37.3%), SPPB <10 (28.5%), and VES-13 >3 (15.4%). Within 30 days of PD, 46%
      experienced a severe complication (Clavien-Dindo grade >=III). In regression
      analyses controlling for age, the body mass index, the American Society of
      Anesthesiologists score, and comorbidity burden, Fried's "exhaustion" predicted
      major complications [odds ratio (OR) = 4.06; P = 0.01], longer hospital stays
      (beta = 0.27; P = 0.02), and surgical intensive care unit admissions (OR = 4.30;
      P = 0.01). Both SPPB (OR = 0.61; P = 0.04) and older age predicted discharge to a
      rehabilitation facility (OR = 1.1; P < 0.05) and age correlated with a lower
      likelihood of hospital readmission (OR = 0.94; P = 0.02). CONCLUSIONS:
      Controlling for standard preoperative assessments, worse scores on GA
      prospectively and independently predicted important adverse outcomes. Geriatric
      assessment may help identify older patients at high risk for complications from
      PD.

PMID- 24096758
TI  - Comparison of treatment effect estimates from prospective nonrandomized studies
      with propensity score analysis and randomized controlled trials of surgical
      procedures.
AB  - OBJECTIVE: We aimed to compare treatment effect estimates from NRSs with PS
      analysis and RCTs of surgery. BACKGROUND: Evaluating a surgical procedure in
      randomized controlled trials (RCTs) is challenging. Nonrandomized studies (NRSs)
      involving use of propensity score (PS) analysis to limit bias are of increasing
      interest. DESIGN: Meta-epidemiological study. METHODS: We systematically searched
      MEDLINE via PubMed for all prospective NRSs with PS analysis evaluating a
      surgical procedure. Related RCTs, addressing the same clinical questions, were
      systematically retrieved. Our primary outcome of interest was all-cause
      mortality. We also selected 1 subjective outcome. We calculated the summary odds
      ratios (OR) for each study design, the ratio of OR (ROR) between the designs and
      the summary ROR across clinical questions. An ROR<1 indicated that the
      experimental intervention is more favorable in NRSs with PS analysis than RCTs.
      RESULTS: We retrieved 70 reports of NRSs with PS analysis and 94 related RCTs
      evaluating 31 clinical questions, of which 22 assessed all-cause mortality and 26
      a subjective outcome. The combined ROR for all-cause mortality was 0.83 (95%
      confidence interval: 0.65-1.04). For subjective outcomes, the combined ROR was
      1.07 (0.87-1.33). CONCLUSIONS: There was no statistically significant difference
      in treatment effect between NRSs with PS analysis and RCTs. Prospective NRSs with
      suitable and careful PS analysis can be relied upon as evidence when RCTs are not
      possible.

PMID- 24096759
TI  - Is surveillance imaging effective for detecting surgically treatable recurrences
      in patients with melanoma? A comparative analysis of stage-specific surveillance
      strategies.
AB  - OBJECTIVE: To guide resource utilization, we aimed to determine the impact of
      routine surveillance imaging for the detection of melanoma recurrences amenable
      to surgical resection with curative intent. BACKGROUND: The National
      Comprehensive Cancer Network guidelines for melanoma surveillance are largely
      consensus based. METHODS: Using single-institution, patient-level data (n =
      1600), transition probabilities were calculated for a Markov model simulating the
      natural history of patients with stage I-III melanoma. As a base estimate,
      imaging was assumed to detect regional and distant recurrences of which 80% and
      20% could be surgically treated with curative intent, respectively. Sensitivity
      analyses were conducted for all point estimates. For each disease stage, we
      calculated the number of surgically treatable regional or distant recurrence
      detected during 5 years per 10,000 patients undergoing computed tomography (CT)
      or positron emission tomography (PET)/CT scans at 6- or 12-month intervals. The
      associated positive and negative predictive values and life expectancy were also
      calculated and compared with clinical examination alone. RESULTS: At 5-year
      follow-up, CT or PET/CT at 6-month intervals detected surgically treatable
      regional or distant recurrence in 6.4% of patients with stage I, 18.5% of stage
      II, and 33.1% of stage III disease; 12-month intervals decreased the rates to
      3.0%, 7.9%, and 13.0%, respectively. The high false-positive rates of CT (20%)
      and PET/CT (9%) resulted in overall low positive predictive values. However, both
      CT and PET/CT effectively predicted absence of disease. Life-expectancy gains
      were minimal (<= 2 months) for all groups. CONCLUSIONS: The effectiveness of
      routine surveillance imaging for detecting treatable melanoma recurrences is
      limited. Even in patients with stage III disease, only minimal gains in life
      expectancy were achieved.

PMID- 24096760
TI  - Microwave ablation for hepatic malignancies: a multiinstitutional analysis.
AB  - OBJECTIVE: This study hypothesized that tumor size, number of tumors, surgical
      approach, and tumor histology significantly affected microwave ablation (MWA)
      success and recurrence-free survival. BACKGROUND: Although many hepatobiliary
      centers have adopted MWA, the factors that influence local control are not well
      described. METHODS: Consecutive patients with hepatic malignancy treated by MWA
      were included from 4 high-volume institutions (2003-2011) and grouped by
      histology: hepatocellular carcinoma (HCC), colorectal liver metastases,
      neuroendocrine liver metastases, and other cancers. Independent significance of
      outcome variables was established with logistic regression and Cox proportional
      hazards models. RESULTS: Four hundred fifty patients were treated with 473
      procedures (139 HCC, 198 colorectal liver metastases, 61 neuroendocrine liver
      metastases, and 75 other) for a total of 875 tumors. Median follow-up was 18
      months. Concurrent hepatectomy was performed in 178 patients (38%), and when
      performed was associated with greater morbidity. Complete ablation was confirmed
      for 839 of 865 tumors (97.0%) on follow-up cross-sectional imaging (10 were
      unevaluable). A surgical approach (open, laparoscopic, or percutaneous) had no
      significant impact on complication rates, recurrence, or survival. The local
      recurrence rate was 6.0% overall and was highest for HCC (10.1%, P = 0.045) and
      percutaneously treated lesions (14.1%, P = 0.014). In adjusted models, tumor size
      3 cm or more predicted poorer recurrence-free survival (hazard ratio: 1.60, 95%
      CI: 1.02-2.50, P = 0.039). CONCLUSIONS: In this large data set, patients with 3
      cm or more tumors showed a propensity for early recurrence, regardless of
      histology. Higher rates of local recurrence were noted in HCC patients, which may
      reflect underlying liver disease. There were no significant differences in
      morbidity or survival based on the surgical approach; however, local recurrence
      rates were highest for percutaneously ablated tumors.

PMID- 24096761
TI  - Chronic subdural hematoma management: a systematic review and meta-analysis of
      34,829 patients.
AB  - OBJECTIVE: To compare the efficacy and safety of multiple treatment modalities
      for the management of chronic subdural hematoma (CSDH) patients. BACKGROUND:
      Current management strategies of CSDHs remain widely controversial. Treatment
      options vary from medical therapy and bedside procedures to major operative
      techniques. METHODS: We searched MEDLINE (PubMed and Ovid), EMBASE, CINAHL,
      Google scholar, and the Cochrane library from January 1970 through February 2013
      for randomized and observational studies reporting one or more outcome following
      the management of symptomatic patients with CSDH. Independent reviewers evaluated
      the quality of studies and abstracted the data on the safety and efficacy of
      percutaneous bedside twist-drill drainage, single or multiple operating room burr
      holes, craniotomy, corticosteroids as a main or adjuvant therapy, use of drains,
      irrigation of the hematoma cavity, bed rest, and treatment of recurrences
      following CSDH management. Mortality, morbidity, cure, and recurrence rates were
      examined for each management option. Randomized, prospective, retrospective, and
      overall observational studies were analyzed separately. Pooled estimates,
      confidence intervals (CIs), and relative risks (RRs) were calculated for all
      outcomes using a random-effects model. RESULTS: A total of 34,829 patients from
      250 studies met our eligibility criteria. Sixteen trials were randomized, and the
      remaining 234 were observational. We included our unpublished single center
      series of 834 patients. When comparing percutaneous bedside drainage to operating
      room burr hole evacuation, there was no significant difference in mortality (RR,
      0.69; 95% CI, 0.46-1.05; P = 0.09), morbidity (RR, 0.45; 95% CI, 0.2-1.01; P =
      0.05), cure (RR, 1.05; 95% CI, 0.98-1.11; P = 0.15), and recurrence rates (RR, 1;
      95% CI, 0.66-1.52; P = 0.99). Higher morbidity was associated with the adjuvant
      use of corticosteroids (RR, 1.97; 95% CI, 1.54-2.45; P = 0.005), with no
      significant improvement in recurrence and cure rates. The use of drains following
      CSDH drainage resulted in a significant decrease in recurrences (RR, 0.46; 95%
      CI, 0.27-0.76; P = 0.002). Craniotomy was associated with higher complication
      rates if considered initially (RR, 1.39; 95% CI, 1.04-1.74; P = 0.01); however,
      craniotomy was superior to minimally invasive procedures in the management of
      recurrences (RR, 0.22; 95% CI, 0.05-0.85; P = 0.003). CONCLUSIONS: Percutaneous
      bedside twist-drill drainage is a relatively safe and effective first-line
      management option. These findings may result in potential health cost savings and
      eliminate perioperative risks related to general anesthetic.

PMID- 24096762
TI  - Impact of epidural analgesia on mortality and morbidity after surgery: systematic
      review and meta-analysis of randomized controlled trials.
AB  - OBJECTIVE: To quantify benefit and harm of epidural analgesia, compared with
      systemic opioid analgesia, in adults having surgery under general anesthesia.
      BACKGROUND: It remains controversial whether adding epidural analgesia to general
      anesthesia decreases postoperative morbidity and mortality. METHODS: We searched
      CENTRAL, EMBASE, PubMed, CINAHL, and BIOSIS till July 2012. We included
      randomized controlled trials comparing epidural analgesia (with local
      anesthetics, lasting for >= 24 hours postoperatively) with systemic analgesia in
      adults having surgery under general anesthesia, and reporting on mortality or any
      morbidity endpoint. RESULTS: A total of 125 trials (9044 patients, 4525 received
      epidural analgesia) were eligible. In 10 trials (2201 patients; 87 deaths),
      reporting on mortality as a primary or secondary endpoint, the risk of death was
      decreased with epidural analgesia (3.1% vs 4.9%; odds ratio, 0.60; 95% confidence
      interval, 0.39-0.93). Epidural analgesia significantly decreased the risk of
      atrial fibrillation, supraventricular tachycardia, deep vein thrombosis,
      respiratory depression, atelectasis, pneumonia, ileus, and postoperative nausea
      and vomiting, and also improved recovery of bowel function, but significantly
      increased the risk of arterial hypotension, pruritus, urinary retention, and
      motor blockade. Technical failures occurred in 6.1% of patients. CONCLUSIONS: In
      adults having surgery under general anesthesia, concomitant epidural analgesia
      reduces postoperative mortality and improves a multitude of cardiovascular,
      respiratory, and gastrointestinal morbidity endpoints compared with patients
      receiving systemic analgesia. Because adverse effects and technical failures
      cannot be ruled out, individual risk-benefit analyses and professional care are
      recommended.

PMID- 24096763
TI  - Hepatic resection associated with good survival for selected patients with
      intermediate and advanced-stage hepatocellular carcinoma.
AB  - OBJECTIVE: The efficacy and safety of hepatic resection (HR) to treat patients
      with Barcelona Clinic Liver Cancer (BCLC) stage B and C hepatocellular carcinoma
      (HCC) was retrospectively assessed. BACKGROUND: Although guidelines from the
      European Association for the Study of Liver Disease and the American Association
      for the Study of Liver Disease do not recommend HR for treating BCLC stage B/C
      HCC, several Asian and European studies have come to the opposite conclusions.
      METHODS: A consecutive sample of 1259 patients with BCLC stage B/C HCC who
      underwent HR (n = 908) or transarterial chemoembolization (TACE, n = 351) were
      included. Moreover, propensity score-matched patients were analyzed to adjust for
      any baseline differences. In parallel with this retrospective clinical study, the
      MEDLINE database was searched for studies evaluating the efficacy and safety of
      HR for BCLC stage B/C HCC. RESULTS: Among our patient sample, the 90-day
      mortality rate in the HR group was 3.1%. HR provided a survival benefit over TACE
      at 1, 3, and 5 years (88% vs 81%, 62% vs 33%, and 39% vs 16%, respectively; all P
      < 0.001). Propensity scoring and subgroup analyses based on tumor size, tumor
      number, presence or absence of macrovascular invasion, and portal hypertension
      (PHT) also showed that HR was associated with better long-term survival than
      TACE. All 36 studies identified in our literature search reported that HR is
      associated with good long-term survival and low morbidity. Multivariate analyses
      revealed that alpha-fetoprotein more than or equal to 400 ng/mL, diabetes
      mellitus, macrovascular invasion, and PHT are independent predictors of poor
      prognosis in patients with BCLC stage B/C HCC. CONCLUSIONS: Our clinical and
      literature analyses suggest that in patients with HCC with preserved liver
      function, the presence of large, solitary tumors, multinodular tumors,
      macrovascular invasion, or PHT are not contraindications for HR.

PMID- 24096764
TI  - A preoperative neutrophil to lymphocyte ratio of 3 predicts disease-free survival
      after curative elective colorectal cancer surgery.
AB  - OBJECTIVE: This study aims to determine the role of the neutrophil to lymphocyte
      ratio (NLR) as a prognostic marker for patients with nonmetastatic colorectal
      cancer undergoing curative resection. BACKGROUND: An NLR reflects a systematic
      inflammatory response, with some evidence suggesting that an elevated
      preoperative NLR of more than 5.0 is associated with poorer survival in patients
      with colorectal cancer. METHODS: Data from 506 consecutive patients with a
      diagnosis of nonmetastatic colorectal adenocarcinoma undergoing surgical
      resection between 2006 and 2011 were included. Receiver operating characteristic
      curve analysis was used to identify the optimal value for NLR in relation to
      disease-free and overall survival. Univariate and multivariate Cox regression
      models were used to determine the role of NLR after stratification by several
      clinicopathological factors. Patients were followed by a standardized protocol
      until February 2013. RESULTS: Median follow-up was 45 months [interquartile
      range, 21-65]. Multivariate Cox regression analysis identified an NLR of more
      than 3 as an independent prognostic factor for disease-free survival (odds ratio
      = 2.41; 95% confidence interval = 1.12-5.15; P = 0.024) but not for overall
      survival (odds ratio = 1.23; 95% confidence interval = 0.80-1.90; P = 0.347). A
      high NLR was significantly associated with older age, higher T and N stages, the
      presence of microvascular invasion, low preoperative albumin levels, and higher
      ASA (American Society of Anesthesiologists) status of the patient. CONCLUSIONS:
      For patients with colorectal cancer, a preoperative NLR of more than 3.0 may be
      an independent prognostic factor for disease-free survival. Considering this in
      addition to well-established prognostic variables may improve the processes of
      identifying patients at higher risk of recurrence who would benefit from adjuvant
      therapies or more frequent surveillance, thereby providing more personalized
      cancer care.

PMID- 24096765
TI  - Reply to letter: "Fibrin sealants do not prevent resection surface-related
      complications after liver resection".

PMID- 24096766
TI  - Residual esophageal cancer after neoadjuvant chemoradiotherapy frequently
      involves the mucosa and submucosa.
AB  - OBJECTIVES: To gain insight into the exact location of residual esophageal cancer
      in the esophageal wall and regional lymph nodes after neoadjuvant
      chemoradiotherapy (nCRT) and to determine the pattern of regression. BACKGROUND:
      Data from the recently published chemoradiotherapy for oesophageal cancer
      followed by surgery study trial showed that 49% of squamous cell carcinomas and
      23% of adenocarcinomas had a pathologically complete response (pCR) in the
      resection specimen after nCRT. These results impose the ethical imperative to
      reconsider the necessity of esophagectomy with its substantial morbidity and
      mortality in patients with pCR. However, it remains challenging to accurately
      identify these patients before resection. METHODS: Between January 2003 and July
      2011, all patients with esophageal cancer in a tertiary referral center, who
      underwent nCRT (5 weekly courses of carboplatin and paclitaxel plus 41.4 Gy
      concurrent radiotherapy) and surgical resection, were analyzed. The resection
      specimens were carefully re-evaluated by an experienced gastrointestinal
      pathologist. Tumor regression grade (TRG) was meticulously scored for each
      specific layer of the esophageal wall and for all removed lymph nodes. RESULTS:
      One hundred two consecutive patients were included. Seventy-one (70%) of 102
      patients were noncomplete responders (>=TRG2) and in 63 of these patients (89%),
      residual tumor cells were seen in the mucosa and/or submucosa. Five of 8 patients
      without involvement of the mucosa and the submucosa had isolated remnants in the
      muscle layer (5/102 = 5%); the other 3 patients had tumor cells only in a single
      lymph node (3/102 = 3%). The surrounding stroma showed the highest percentage of
      TRG1 ( = pCR: 47%). In patients with pretreatment lymph node positivity, the
      percentage of TRG1 in all lymph nodes was also favorable (52%). Overall
      regression showed a nonrandom mixed pattern of both concentric regression and
      regression toward the lumen. CONCLUSIONS: After nCRT for esophageal cancer, both
      the mucosa and the submucosa show frequent residual malignant involvement. The
      surrounding stroma and the regional lymph nodes show the highest percentage of
      pCR and the overall regression pattern is most frequently a mixed pattern of both
      concentric regression and regression toward the lumen. This overall regression
      pattern lends support to careful testing of a wait-and-see approach in a subgroup
      of patients with esophageal cancer after nCRT.

PMID- 24096767
TI  - Is the Whipple procedure harmful for long-term outcome in treatment of chronic
      pancreatitis? 15-years follow-up comparing the outcome after pylorus-preserving
      pancreatoduodenectomy and Frey procedure in chronic pancreatitis.
AB  - OBJECTIVE: The aim of this study was to report on 15-year long-term results of a
      randomized controlled trial comparing extended drainage procedure (Frey) and
      classical resectional procedure [pylorus-preserving pancreatoduodenectomy (PD)]
      in patients with chronic pancreatitis. BACKGROUND: Chronic pancreatitis is a
      common inflammatory disease with a prevalence of 10 to 30 cases per 100,000
      inhabitants. It is characterized by the progressive conversion of pancreatic
      parenchyma to fibrous tissue. Different surgical procedures are used in treatment
      of persistent pain. METHODS: Sixty-four patients suffering from chronic
      pancreatitis with inflammatory mass in the pancreatic head were randomly assigned
      in 2 treatment groups (PD, n = 32) and (Frey, n = 32). The perioperative course
      of the randomized controlled trial and the 7 years follow-up have been previously
      published. All participating patients were contacted with a standardized,
      validated questionnaire (EORTC QLQ C30) to evaluate the long-term survival,
      quality-of-life pain, and exocrine and endocrine function. RESULTS: In the 15
      year long-term follow-up, the pain control was good and comparable between both
      groups, but the quality of life was better after Frey procedure in regard of the
      physical status [PD: 100 (0-100) vs PD: 60 (0-100) (P = 0.011)]. No significant
      differences in terms of the Pain Score were detected between both groups [PD: 7
      (0-100) vs Frey 4 (0-100) P = 0.258]. Seven patients after Frey OP and 6 patients
      after PD were free of pain. Analyzing the postoperative overall survival, a
      higher long-term mortality was found after PD (53%) than that found after Frey
      procedure (30%) resulting in a longer mean survival (14.5 +/- 0.8 vs 11.3 +/- 0.8
      years; P = 0.037). No correlation between endocrine or exocrine pancreatic
      function and pain was found, whereas continuous alcohol consumption was
      associated with poorer outcome regarding quality of life (P < 0.001) and pain
      score (P < 0.001). CONCLUSIONS: PD and Frey procedure provide good and permanent
      pain relief and improvement of the quality of life in long-term follow-up. In
      addition, a longer survival was found after the organ sparing resection. Together
      with better short-term results, the organ-sparing procedure seems to be favorable
      in treatment of chronic pancreatitis.

PMID- 24096769
TI  - Antecolic versus retrocolic route of the gastroenteric anastomosis after
      pancreatoduodenectomy: a randomized controlled trial.
AB  - OBJECTIVE: To investigate the relationship between the route of gastroenteric
      (GE) reconstruction after pancreatoduodenectomy (PD) and the postoperative
      incidence of delayed gastric emptying (DGE). BACKGROUND: DGE is one of the most
      common complications after PD. Recent studies suggest that an antecolic route of
      the GE reconstruction leads to a lower incidence of DGE, compared to a retrocolic
      route. In a nonrandomized comparison within our trial center, we found no
      difference in DGE after antecolic or retrocolic GE reconstruction. METHODS: Ten
      middle- to high-volume centers participated in the patient inclusion. Patients
      scheduled for PD who gave written informed consent were included and randomized
      during surgery after resection. Standard operation was a pylorus-preserving PD.
      Primary endpoint was DGE. Secondary endpoints included other complications and
      length of hospital stay. RESULTS: There were 125 patients in the retrocolic
      group, and 121 patients in the antecolic group. Baseline and treatment
      characteristics did not differ between the study groups. In the retrocolic group,
      45 patients (36%) developed clinically relevant DGE compared with 41 (34%) in the
      antecolic group (absolute risk difference: 2.1%; 95% confidence interval: -9.8%
      to 14.0%). There were no differences in need for postoperative (par)enteral
      nutritional support, other complications, hospital mortality, and median length
      of hospital stay. CONCLUSIONS: The route of GE reconstruction after PD does not
      influence the postoperative incidence of DGE or other complications. The etiology
      and treatment of DGE, which occurs frequently after both procedures, need further
      investigation. The GE reconstruction after PD should be routed according to the
      surgeon's preference.

PMID- 24096770
TI  - Variation in practice and resource utilization associated with the diagnosis and
      management of appendicitis at freestanding children's hospitals: implications for
      value-based comparative analysis.
AB  - OBJECTIVE: To characterize the scope and magnitude of practice variation
      associated with the diagnosis and treatment of appendicitis at freestanding
      children's hospitals. BACKGROUND: Variation in care has been associated with poor
      outcomes and is believed to be a key driver of excess health care spending.
      METHODS: Retrospective cohort study of 13,328 patients treated with appendicitis
      at 34 children's hospitals (9/2010-9/2011). Patients were divided into
      complicated and uncomplicated cohorts and examined for interhospital variation in
      the use of diagnostic imaging (computed tomography or ultrasonography),
      laboratory tests, parenteral nutrition (PN), peripherally inserted central
      catheters (PICC), and hospital cost. The number and distribution of statistical
      outliers were calculated for all measures. RESULTS: Significant variation was
      found for all measures, including a 3.5-fold difference in preoperative imaging
      (aggregate rate: 49.0%, range across hospitals: 21.2%-73.5%, P < 0.001) and a 5
      fold difference in preoperative laboratory utilization (aggregate median: 2
      tests/encounter, range: 1-5 tests/encounter, P < 0.001). For patients with
      complicated appendicitis, we characterized a 12-fold difference in postoperative
      imaging (aggregate rate: 19.4%, range: 4.9%-61.6%, P < 0.001), a 48-fold
      difference in PICC lines (aggregate rate: 18.9%, range: 1.7%-81.8%, P < 0.001),
      and a 100-fold difference in PN utilization (aggregate rate: 9.3%, range: 0.4%
      42.0%, P < 0.001). Median hospital cost differed 4-fold for patients with
      uncomplicated disease (aggregate median: $6804, range: $4200-$16,796, P < 0.001)
      and 4.6-fold for patients with complicated disease (aggregate median: $13,138,
      range: $5419-$24,779, P < 0.001). Statistical outliers on the basis of high and
      low utilization were identified for all measures. CONCLUSIONS: Significant
      variation exists in practice, resource utilization, and treatment-related cost
      associated with the management of appendicitis at freestanding children's
      hospitals. Value-based measures are needed for benchmarking and to prioritize
      collaborative quality improvement efforts.

PMID- 24096768
TI  - Waist circumference and waist/hip ratio are better predictive risk factors for
      mortality and morbidity after colorectal surgery than body mass index and body
      surface area.
AB  - OBJECTIVES: To determine whether body fat distribution, measured by waist
      circumference (WC) and waist/hip ratio (WHR), is a better predictor of mortality
      and morbidity after colorectal surgery than body mass index (BMI) or body surface
      area (BSA). BACKGROUND: Obesity measured by BMI is not a consistent risk factor
      for postoperative mortality and morbidity after abdominal surgery. Studies in
      metabolic and cardiovascular diseases have shown WC and WHR to be better outcome
      predictors than BMI. METHODS: A prospective multicenter international study was
      conducted among patients undergoing elective colorectal surgery. The WHR, BMI,
      and BSA were derived from body weight, height, and waist and hip circumferences
      measured preoperatively. Uni- and multivariate analyses were performed to
      identify risk factors for postoperative outcomes. RESULTS: A total of 1349
      patients (754 men) from 38 centers in 11 countries were included. Increasing WHR
      significantly increased the risk of conversion [odds ratio (OR) = 15.7, relative
      risk (RR) = 4.1], intraoperative complications (OR = 11.0, RR = 3.2),
      postoperative surgical complications (OR = 7.7, RR = 2.0), medical complications
      (OR = 13.2, RR = 2.5), anastomotic leak (OR = 13.7, RR = 3.3), reoperations (OR =
      13.3, RR = 2.9), and death (OR = 653.1, RR = 21.8). Both BMI (OR = 39.5, RR =
      1.1) and BSA (OR = 4.9, RR = 3.1) were associated with an increased risk of
      abdominal wound complication. In multivariate analysis, the WHR predicted
      intraoperative complications, conversion, medical complications, and
      reinterventions, whereas BMI was a risk factor only for abdominal wall
      complications; BSA did not reach significance for any outcome. CONCLUSIONS: The
      WHR is predictive of adverse events after elective colorectal surgery. It should
      be used in routine clinical practice and in future risk-estimating systems.

PMID- 24096771
TI  - The 14q32 microRNA-487b targets the antiapoptotic insulin receptor substrate 1 in
      hypertension-induced remodeling of the aorta.
AB  - OBJECTIVES: To study the role of microRNAs in hypertension-induced vascular
      pathology before the onset of symptoms of severe cardiovascular disease.
      BACKGROUND: MicroRNAs play a crucial role in cardiovascular disease. However,
      microRNAs are often studied in full-blown cardiovascular disease models, not
      during development of cardiovascular pathology. METHODS: Angiotensin II was
      infused into healthy adult rats, inducing chronic hypertension, and microRNA
      expression profiles were obtained. The most prominently regulated microRNA, miR
      487b, was further investigated, using primary cultures of rat aortic and human
      umbilical cord arterial cells. RESULTS: MiR-487b is predicted to target insulin
      receptor substrate 1 (IRS1). IRS1 plays an important role in both insulin
      signaling and cell proliferation and survival. IRS1 mRNA and protein levels were
      downregulated in aortae of hypertensive rats. MiR-487b binds directly to both rat
      and human IRS1 3'UTR and inhibits reporter gene expression in vitro. In primary
      rat and human arterial adventitial fibroblasts, inhibition of miR-487b leads to
      upregulation of IRS1 expression. Upregulation of miR-487b had the opposite
      effect, confirming direct targeting of IRS1 by miR-487b.Immunohistochemistry of
      aortic cross sections and rt/qPCR analyses of the separate aortic wall layers
      showed that both IRS1 and miR-487b were present mainly in the adventitia and less
      or not at all in the intima and tunica media. IRS1 expression in adventitial
      fibroblasts was predominantly nuclear and nuclear IRS1 is known to have
      antiapoptotic effects. Indeed, inhibition of miR-487b protected adventitial
      fibroblasts, and also medial smooth muscle cells, against serum starvation
      induced apoptosis and increased cell survival. CONCLUSIONS: Angiotensin II
      induced hypertension leads to upregulation of miR-487b, which targets IRS1. Via
      downregulation of IRS1, miR-487b can contribute to cell death and loss of
      adventitial and medial integrity during hypertension-induced vascular pathology.

PMID- 24096772
TI  - Prevalence and topography of lymph node metastases in early esophageal and
      gastric cancer.
AB  - OBJECTIVE: To determine the prevalence and localization of lymph node metastases
      in patients with pT1 carcinoma of the esophagus, esophagogastric junction, and
      stomach. BACKGROUND: Retrospective analysis and topographic description. METHODS:
      We included 793 consecutive patients with pT1 carcinomas who underwent primary
      surgery for squamous cell carcinoma (SCC) of the esophagus, adenocarcinomas of
      the esophagogastric junction (AEG), or gastric cancer (GC). Clinical records and
      pathology reports were reviewed, and the prevalence and topography of lymph node
      metastases were identified. RESULTS: The prevalence of lymph node metastases in
      SCC, AEG, and GC was 7%, 0%, and 5% for pT1a tumors and 24%, 18%, and 14% for
      pT1b tumors, respectively. Positive lymph node status was associated with worse
      overall survival (P<0.001). Not only infiltration of the submucosa (P=0.002) but
      also lymphatic vessel invasion (P<0.001), multifocal tumor growth (P=0.001),
      lower patient age (P=0.001), and poor tumor differentiation (P=0.05) were
      associated with nodal disease. These 5 parameters allowed the compilation of a
      nomogram to estimate the individual risk of lymph node metastases. In SCC, lymph
      node metastases were found from the neck to the celiac axis. In AEG, nodal
      disease was limited to the lower mediastinum and the D1 compartment. In GC,
      lymphatic spread exceeded the D1 compartment in 7% of node positive patients.
      CONCLUSIONS: Risk estimation for lymph node metastases should not be based on
      depth of tumor infiltration alone but additional clinicopathological parameters
      should also be considered. The extent of lymphadenectomy in surgical procedures
      should respect the presented topography of lymph node metastases.

PMID- 24096773
TI  - Treating anxiety in the presence of medical comorbidity: calmly moving forward.
AB  - Patients with chronic medical conditions (CMCs) and a comorbid anxiety or mood
      disorder tend to report more symptoms and experience poorer treatment outcomes
      compared with those without mental health comorbidity. Although the benefits to
      be derived from treating depression in patients with CMCs have begun to be
      quantified, particularly among those with cardiovascular disease, our
      understanding of the benefits of treating anxiety in patients with CMCs is far
      less developed. Improving care for patients with CMCs is one of the major
      challenges facing medicine today because patients with multiple chronic diseases
      account for most health care costs. Emerging evidence indicates that integrated
      or "blended" collaborative care strategies that treat both the psychiatric and
      physical conditions together tend to produce greater improvements in mood
      symptoms and control of CMCs compared with programs that target the psychiatric
      condition alone. We review a new report, published in this issue of Psychosomatic
      Medicine, from the National Institutes of Mental Health-funded multisite
      Coordinated Anxiety Learning and Management trial, that shines new attention on
      anxiety disorders and medical comorbidity. We place their findings in context
      with these new blended care models that are potentially more powerful, scalable,
      cost-effective, and readily delivered through existing CMC programs. 

PMID- 24096774
TI  - Adherence to psychiatric treatments and the public image of psychiatry.

PMID- 24096777
TI  - Neurobiological advances identify novel antidepressant targets.

PMID- 24096776
TI  - Diagnosis and classification of disorders specifically associated with stress:
      proposals for ICD-11.
AB  - The diagnostic concepts of post-traumatic stress disorder (PTSD) and other
      disorders specifically associated with stress have been intensively discussed
      among neuro- and social scientists, clinicians, epidemiologists, public health
      planners and humanitarian aid workers around the world. PTSD and adjustment
      disorder are among the most widely used diagnoses in mental health care
      worldwide. This paper describes proposals that aim to maximize clinical utility
      for the classification and grouping of disorders specifically associated with
      stress in the forthcoming 11th revision of the International Classification of
      Diseases (ICD-11). Proposals include a narrower concept for PTSD that does not
      allow the diagnosis to be made based entirely on non-specific symptoms; a new
      complex PTSD category that comprises three clusters of intra- and interpersonal
      symptoms in addition to core PTSD symptoms; a new diagnosis of prolonged grief
      disorder, used to describe patients that undergo an intensely painful, disabling,
      and abnormally persistent response to bereavement; a major revision of
      "adjustment disorder" involving increased specification of symptoms; and a
      conceptualization of "acute stress reaction" as a normal phenomenon that still
      may require clinical intervention. These proposals were developed with specific
      considerations given to clinical utility and global applicability in both low-
      and high-income countries. 

PMID- 24096775
TI  - Urbanicity, social adversity and psychosis.
AB  - In recent years, there has been increasing interest in research on geographical
      variation in the incidence of schizophrenia and other psychoses. In this paper,
      we review the evidence on variation in incidence of schizophrenia and other
      psychoses in terms of place, as well as the individual- and area-level factors
      that account for this variation. We further review findings on potential
      mechanisms that link adverse urban environment and psychosis. There is evidence
      from earlier and more recent studies that urbanicity is associated with an
      increased incidence of schizophrenia and non-affective psychosis. In addition,
      considerable variation in incidence across neighbourhoods has been observed for
      these disorders. Findings suggest it is unlikely that social drift alone can
      fully account for geographical variation in incidence. Evidence further suggests
      that the impact of adverse social contexts - indexed by area-level exposures such
      as population density, social fragmentation and deprivation - on risk of
      psychosis is explained (confounding) or modified (interaction) by environmental
      exposures at the individual level (i.e., cannabis use, social adversity,
      exclusion and discrimination). On a neurobiological level, several studies
      suggest a close link between social adversity, isolation and stress on the one
      hand, and monoamine dysfunction on the other, which resembles findings in
      schizophrenia patients. However, studies directly assessing correlations between
      urban stress or discrimination and neurobiological alterations in schizophrenia
      are lacking to date. 

PMID- 24096778
TI  - Taking disease seriously in DSM.

PMID- 24096779
TI  - The next stage for diagnosis: validity through utility.

PMID- 24096780
TI  - Non-adherence to medication in patients with psychotic disorders: epidemiology,
      contributing factors and management strategies.
AB  - Although non-adherence is common across all branches of medicine, psychotic
      disorders pose additional challenges that increase its risk. Despite the
      importance of non-adherence, clinicians generally spend too little time on
      assessing and addressing adherence attitudes and behaviors. Importantly, how
      adherence is measured significantly impacts the findings, and the most frequently
      employed methods of asking patients or judging adherence indirectly based on
      efficacy or tolerability information have poor validity. Novel technologies are
      being developed that directly assess adherence and that can also be used to both
      provide real-time feedback to clinicians and serve as an intervention with
      patients. Several treatments are available that can positively impact adherence.
      Among psychosocial interventions, those combining multiple approaches and
      involving multiple domains seem to be most effective. Although long-acting
      injectable antipsychotics are theoretically a very powerful tool to assure
      adherence and signal non-adherence, recent results from randomized controlled
      trials failed to show superiority compared to oral antipsychotics. These data are
      in contrast to nationwide cohort studies and mirror-image studies, which arguably
      include more representative patients receiving long-acting antipsychotics in
      clinical practice. This disconnect suggests that traditional randomized
      controlled trials are not necessarily the best way to study interventions that
      are thought to work via reducing non-adherence. Clearly, non-adherence is likely
      to remain a major public health problem despite treatment advances. However,
      increasing knowledge about factors affecting adherence and leveraging novel
      technologies can enhance its early assessment and adequate management,
      particularly in patients with psychotic disorders. 

PMID- 24096781
TI  - Progress in compliance research and intervention: a commentary.

PMID- 24096782
TI  - Managing non-adherence and the 3 Cs: collaboration, cash and coercion.

PMID- 24096783
TI  - Talking about adherence.

PMID- 24096784
TI  - Adherence/compliance: a multifaceted challenge.

PMID- 24096785
TI  - Practical strategies for improving adherence to medication and outcomes.

PMID- 24096786
TI  - Non-adherence and its consequences: understanding the nature of relapse.

PMID- 24096787
TI  - The enduring challenge of antipsychotic non-adherence.

PMID- 24096788
TI  - Should we listen and talk more to our patients?

PMID- 24096789
TI  - Public health and physician focused strategies to improve medication adherence in
      psychotic disorders.

PMID- 24096792
TI  - Parenting and child mental health: a cross-cultural perspective.
AB  - In its most general instrumental sense, parenting consists of care of the young
      in preparing them to manage the tasks of life. Parents provide childhood
      experiences and populate the environments that guide children's development and
      so contribute to child mental health. Parenting is expressed in cognitions and
      practices. However, parents do not parent, and children do not grow up, in
      isolation, but in multiple contexts, and one notable context of parenting and
      child mental health is culture. Every culture is characterized, and distinguished
      from other cultures, by deep-rooted and widely acknowledged ideas about how one
      needs to feel, think, and act as an adequately functioning member of the culture.
      Insofar as parents subscribe to particular conventions of a culture, they likely
      follow prevailing "cultural scripts" in childrearing. Broadening our definition,
      it is therefore the continuing task of parents also to enculturate children by
      preparing them for the physical, psychosocial, and educational situations that
      are characteristic of their specific culture. Cross-cultural comparisons show
      that virtually all aspects of parenting children are informed by culture: culture
      influences when and how parents care for children, what parents expect of
      children, and which behaviors parents appreciate, emphasize and reward or
      discourage and punish. Thus, cultural norms become manifest in the mental health
      of children through parenting. Furthermore, variations in what is normative in
      different cultures challenge our assumptions about what is universal and inform
      our understanding of how parent-child relationships unfold in ways both
      culturally universal and specific. This essay concerns the contributions of
      culture to parenting and child mental health. No study of a single society can
      address this broad issue. It is possible, however, to learn lessons about
      parenting and child mental health from the study of different societies. 

PMID- 24096791
TI  - Psychotic symptoms are associated with physical health problems independently of
      a mental disorder diagnosis: results from the WHO World Health Survey.
AB  - This study explored whether physical health problems are related to psychotic
      symptoms independently of a mental disorder diagnosis. A total of 224,254
      subjects recruited for the World Health Organization World Health Survey were
      subdivided into those with both a lifetime diagnosis of psychosis and at least
      one psychotic symptom in the 12 months prior to the evaluation, those with at
      least one psychotic symptom in the past 12 months but no lifetime diagnosis of
      psychosis, and those without psychotic symptoms in the past 12 months and without
      a lifetime diagnosis of psychosis. The three groups were compared for the
      presence of medical conditions, health problems, and access to health care.
      Medical conditions and health problems (angina, asthma, arthritis, tuberculosis,
      vision or hearing problems, mouth/teeth problems, alcohol consumption, smoking,
      and accidents), medication consumption, and hospital admissions (but not regular
      health care visits) were more frequent in individuals with psychotic symptoms but
      no psychosis diagnosis, compared to those with no symptoms and no diagnosis. The
      number of medical conditions increased with the number of psychotic symptoms.
      Given the sample analyzed, this trend seems to be independent from the socio
      economic development of the country or the specific health care system. 

PMID- 24096790
TI  - A meta-analysis of cardio-metabolic abnormalities in drug naive, first-episode
      and multi-episode patients with schizophrenia versus general population controls.
AB  - A meta-analysis was conducted to explore the risk for cardio-metabolic
      abnormalities in drug naive, first-episode and multi-episode patients with
      schizophrenia and age- and gender- or cohort-matched general population controls.
      Our literature search generated 203 relevant studies, of which 136 were included.
      The final dataset comprised 185,606 unique patients with schizophrenia, and 28
      studies provided data for age- and gender-matched or cohort-matched general
      population controls (n=3,898,739). We found that multi-episode patients with
      schizophrenia were at increased risk for abdominal obesity (OR=4.43; CI=2.52
      7.82; p<0.001), hypertension (OR=1.36; CI=1.21-1.53; p<0.001), low high-density
      lipoprotein cholesterol (OR=2.35; CI=1.78-3.10; p<0.001), hypertriglyceridemia
      (OR=2.73; CI=1.95-3.83; p<0.001), metabolic syndrome (OR=2.35; CI=1.68-3.29;
      p<0.001), and diabetes (OR=1.99; CI=1.55-2.54; p<0.001), compared to controls.
      Multi-episode patients with schizophrenia were also at increased risk, compared
      to first-episode (p<0.001) and drug-naive (p<0.001) patients, for the above
      abnormalities, with the exception of hypertension and diabetes. Our data provide
      further evidence supporting WPA recommendations on screening, follow-up, health
      education and lifestyle changes in people with schizophrenia. 

PMID- 24096793
TI  - How to convince politicians that mental health is a priority.

PMID- 24096794
TI  - Beyond dichotomies: confronting the complexity of how and why individuals come or
      do not come to mental health care.

PMID- 24096795
TI  - Teenage depression: some navigational points for parents and professionals.

PMID- 24096796
TI  - Priority issues in women's mental health.

PMID- 24096797
TI  - My Voice, My Life: a measure based on the consumer model of recovery.

PMID- 24096798
TI  - WPA Scientific Sections.

PMID- 24096799
TI  - WPA publications: opportunities to improve psychiatric research and inform
      clinical care and education.

PMID- 24096800
TI  - The new impact factor of World Psychiatry.

PMID- 24096801
TI  - Greater saphenous venous access as an alternative in children.
AB  - BACKGROUND: In the pediatric population, obtaining venous access in high-risk
      neonates, severely ill children with cardiac anomalies or very young children
      (<10 kg) can be very challenging. In the literature to date, the greater
      saphenous vein has not been primarily used by interventional radiologists as an
      entry site for venous access in children. OBJECTIVE: To demonstrate the utility
      and effectiveness of using the greater saphenous vein as a venous access site for
      the placement of peripherally inserted central catheters in children. MATERIALS
      AND METHODS: This is a retrospective study from a large tertiary care children's
      hospital from November 2010 to August 2012. Peripheral insertion of central
      venous catheters (PICC) using the greater saphenous vein was attempted in 86
      children ranging in age from 3 days to 17 years (mean: 1.8 years). Indications
      included congenital heart disease, urinary tract infection, intravenous access,
      pneumonia, meningitis, total parenteral nutrition, sepsis and other infections.
      All procedures were performed by interventional radiologists. No insertion
      related complications were identified. There was no follow-up planning, but no
      mechanical or infectious complications were brought to our attention. RESULTS: Of
      the 86 patients in whom PICC placement was attempted, placement was successful in
      67 (78%). Forty-two PICCs were placed in the greater saphenous vein at the thigh
      level using US guidance and 25 at the ankle level using anatomical landmarks. The
      mean weight of the 67 patients who underwent successful placement was 9.98 kg,
      with 51 (76%) weighing <10 kg. The mean vessel diameter in placement failures was
      1.35 mm compared to 1.83 mm in successful placement. Inability to obtain venous
      access was the cause of failure in all thigh access sites while inability to
      advance the catheter centrally was the cause of failure for all ankle access
      sites. A total of 1,060 catheter days (with a maximum dwell time of 97 days in
      one patient) were reviewed without complication. CONCLUSION: In children, the
      greater saphenous vein provides a safe, suitable alternative for venous access,
      particularly in very young children (<10 kg) and in a select group of older
      children who are not mobile. In the lower extremities, greater saphenous venous
      puncture and access may be a preferred initial access site in small children to
      preserve future venous access.

PMID- 24096803
TI  - Fetal MRI of hereditary multiple intestinal atresia with postnatal correlation.
AB  - Hereditary multiple intestinal atresia (HMIA) is an extremely uncommon cause of
      congenital bowel obstruction. The morbidity and mortality of this disease differ
      significantly from those of isolated intestinal atresias and non-hereditary forms
      of multiple intestinal atresia. Most notably, despite successful operative
      repairs of the atresias found in this disease, HMIA maintains a 100% lethality
      rate from continued post-operative intestinal failure and an associated severe
      immunodeficiency. We present a case of HMIA evaluated with fetal MRI and
      subsequently diagnosed by a combination of corroborative postnatal imaging with
      surgical exploration and pathological examination. 

PMID- 24096802
TI  - High success rates of sedation-free brain MRI scanning in young children using
      simple subject preparation protocols with and without a commercial mock scanner-
      the Diabetes Research in Children Network (DirecNet) experience.
AB  - BACKGROUND: The ability to lie still in an MRI scanner is essential for obtaining
      usable image data. To reduce motion, young children are often sedated, adding
      significant cost and risk. OBJECTIVE: We assessed the feasibility of using a
      simple and affordable behavioral desensitization program to yield high-quality
      brain MRI scans in sedation-free children. MATERIALS AND METHODS: 222 children (4
      9.9 years), 147 with type 1 diabetes and 75 age-matched non-diabetic controls,
      participated in a multi-site study focused on effects of type 1 diabetes on the
      developing brain. T1-weighted and diffusion-weighted imaging (DWI) MRI scans were
      performed. All children underwent behavioral training and practice MRI sessions
      using either a commercial MRI simulator or an inexpensive mock scanner consisting
      of a toy tunnel, vibrating mat, and video player to simulate the sounds and feel
      of the MRI scanner. RESULTS: 205 children (92.3%), mean age 7 +/- 1.7 years had
      high-quality T1-W scans and 174 (78.4%) had high-quality diffusion-weighted scans
      after the first scan session. With a second scan session, success rates were 100%
      and 92.5% for T1-and diffusion-weighted scans, respectively. Success rates did
      not differ between children with type 1 diabetes and children without diabetes,
      or between centers using a commercial MRI scan simulator and those using the
      inexpensive mock scanner. CONCLUSION: Behavioral training can lead to a high
      success rate for obtaining high-quality T1-and diffusion-weighted brain images
      from a young population without sedation.

PMID- 24096804
TI  - Bodily aesthetic ideals among Latinas with type 2 diabetes: implications for
      treatment adherence, access, and outcomes.
AB  - PURPOSE: The purpose of this study was to examine how attitudes and practices
      related to bodily aesthetic ideals and self-care might inform the engagement of
      Latinas with type 2 diabetes (T2DM). METHODS: Focus groups were used to collect
      qualitative data concerning bodily aesthetic ideals and diabetes management,
      including help-seeking experiences, from Latina women with T2DM (n = 29)
      receiving care through Latino Diabetes Initiative at the Joslin Diabetes Center.
      Focus groups were conducted in Spanish, audiotaped, transcribed, and content
      analyzed. RESULTS: Four main themes emerged: (1) a preference among participants
      for a larger than average body size, although perceptions of attractiveness were
      more closely linked to grooming than body size; bodily dissatisfaction centered
      on diabetes-induced skin changes, virilization, and fatigue rather than weight;
      (2) diabetic complications, especially foot pain, as a major obstacle to
      exercise; (3) fatalistic attitudes regarding the inevitability of diabetes and
      reversal of its complications; and (4) social burdens, isolation, and financial
      stressors as contributing to disease exacerbation. CONCLUSIONS: Interventions
      that emphasize reduced body size may be less effective with Latinas who have T2DM
      than those that emphasize the benefits of exercise and weight loss for skin
      health, energy levels, and reduced virilization.

PMID- 24096805
TI  - The relationship between coping styles in response to unfair treatment and
      understanding of diabetes self-care.
AB  - PURPOSE: This study examined the relationship between coping style and
      understanding of diabetes self-care among African American and white elders in a
      southern Medicare-managed care plan. METHODS: Participants were identified
      through a diabetes-related pharmacy claim or ICD-9 code and completed a computer
      assisted telephone survey in 2006-2007. Understanding of diabetes self-care was
      assessed using the Diabetes Care Profile Understanding (DCP-U) scale. Coping
      styles were classified as active (talk about it/take action) or passive (keep it
      to yourself). Linear regression was used to estimate the associations between
      coping style with the DCP-U, adjusting for age, sex, education, and
      comorbidities. Based on the conceptual model, 4 separate categories were
      established for African American and white participants who displayed active and
      passive coping styles. RESULTS: Of 1420 participants, the mean age was 73 years,
      46% were African American, and 63% were female. Most respondents (77%) exhibited
      active coping in response to unfair treatment. For African American participants
      in the study, active coping was associated with higher adjusted mean DCP-U scores
      when compared to participants with a passive coping style. No difference in DCP-U
      score was noted among white participants on the basis of coping style.
      CONCLUSIONS: Active coping was more strongly associated with understanding of
      diabetes self-care among older African Americans than whites. Future research on
      coping styles may give new insights into reducing diabetes disparities among
      racial/ethnic minorities.

PMID- 24096806
TI  - Primary mucoepidermoid carcinoma of the thyroid gland: a report of three cases
      and review of the literature.
AB  - Mucoepidermoid carcinoma is the most common salivary gland malignancy and it may
      arise anywhere that salivary tissue is present. Mucoepidermoid carcinoma has been
      reported to arise de novo within the thyroid gland, and here, we describe three
      cases of primary mucoepidermoid carcinoma of the thyroid, including clinical
      presentation, diagnostic evaluation, and clinical follow-up, along with a
      discussion of tumor origin and a review of the literature. 

PMID- 24096807
TI  - Usefulness of negative and weak-diffuse pattern of SDHB immunostaining in
      assessment of SDH mutations in paragangliomas and pheochromocytomas.
AB  - This is a confirmatory study about usefulness of SDHB and SDHA immunostaining in
      assessment of SDH mutations in paragangliomas and pheochromocytomas.
      Paraganglioma/pheochromocytoma syndrome (PGL/PCC syndrome) consists of different
      entities, associated with germline mutations in five different genes: SDHD,
      SDHAF2, SDHC, SDHA and SDHB. It has been suggested that negative immunostaining
      of SDHB can be taken as an indicator of the presence of a mutation in one of the
      five SDH genes. We have performed SDHB and SDHA immunohistochemical staining in a
      series of paragangliomas and pheochromocytomas from 64 patients. The patients had
      been previously checked for mutations in SDHD, SDHC and SDHB, but also for
      mutation in RET and VHL. All 14 patients with SDH mutations (9 with SDHB and 5
      with SDHD mutations) exhibited negative or weak-diffuse SDHB staining pattern in
      tumour tissue, whereas cells of the 23 RET mutated and 8 VHL mutated tumours
      showed a positive SDHB immunostaining. Sixteen of the patients that did not
      exhibit a mutation in any gene showed positive SDHB immunostaining in tumour
      tissue, while only three of the patients without mutation exhibited negative
      staining. All patients exhibited positive pattern of SDHA immunostaining. The
      results confirm the value of SDHB immunohistochemical status in assessment of
      germline mutations in PGL/PCC syndrome. 

PMID- 24096808
TI  - Facile synthesis of hydrogenated carbon nanospheres with a graphite-like ordered
      carbon structure.
AB  - We report a synthesis of hydrogenated carbon nanospheres (HCNSs) via a facile
      solvothermal route at low temperatures (60-100  degrees C), using CHCl3 as the
      carbon source and potassium (K) as the reductant. Selective cleavage of the
      relatively lower stable C-Cl bonds (compared to C-H bonds) of the carbon
      precursor (CHCl3) by K metal results in the growth of HCNSs. The diameter of
      HCNSs ranges from 40 to 90 nm. The HCNSs have a graphite-like ordered carbon
      structure in spite of their high degree of hydrogenation. The HCNSs exhibit an
      average Brunauer-Emmett-Teller (BET) surface area of 43 m(2) g(-1), containing a
      small amount of mesopores and macropores in the structure. The nanospheres'
      sample as an anode material for lithium ion batteries (LIBs) has been studied. It
      exhibits a high discharge capacity (3539 mA h g(-1) in the first cycle, 978 mA h
      g(-1) after 50 cycles) and good cycling stability, demonstrating advantages as a
      promising candidate for anode materials in LIBs. The high capacity of the HCNSs
      is due to their unique nanostructures and high percentage hydrogenation, as well
      as hydrogenation induced structural defects. 

PMID- 24096809
TI  - The effects of rise/fall time and plateau time on ocular vestibular evoked
      myogenic potentials.
AB  - Ocular vestibular evoked myogenic potentials (oVEMP) are strongly influenced by
      recording conditions and stimulus parameters. Throughout the published
      literature, a large variety of stimuli is used for eliciting oVEMP. Our objective
      was to determine the effects of different rise/fall times and plateau times on
      oVEMP amplitudes and latencies. 32 healthy subjects were enrolled in the study.
      500 Hz air-conducted tone bursts with the parameters rise-plateau-fall time 0-4
      0, 4-0-4, 2-2-2 and 2-4-2 ms were used for eliciting oVEMP. For all stimuli,
      response prevalences were 100 %. The 4-0-4 ms stimulus generated the smallest
      amplitudes, whereas the 2-2-2 and 0-4-0 ms stimuli achieved the largest
      amplitudes. n1 and p1 latencies were significantly shorter for the 0-4-0 ms than
      for the other stimuli, whereas latencies in response to the 4-0-4 ms stimulus
      were prolonged. Hence, a variety of stimuli is suitable for evoking oVEMP in
      healthy subjects. We recommend a 2-2-2 ms stimulus for clinical testing of oVEMP
      elicited by air conducted sound, because it reproducibly generates oVEMP without
      exposing the ear to unnecessary amounts of acoustic energy.

PMID- 24096810
TI  - Transcervical extirpation of the submandibular gland: the University of Marburg
      experience.
AB  - Surgical excision of the submandibular gland is the treatment of choice for
      lesions affecting this gland. The data of 87 patients, who underwent a
      transcervical extirpation of the submandibular gland as a single operation over
      the past 10 years at a single institution in Germany, were available for
      analysis. Sialolithiasis (73.5%) was the most common reason leading to excision,
      followed by benign (18.5%) and malignant tumors (8%). Complications included
      temporary palsies of the marginal mandibular branch of the facial nerve (5.7%),
      the lingual nerve (5.7%), and the hypoglossal nerve (1.1%), and wound infections
      in the form of hematoma (3.4%) and seroma (1.1%).

PMID- 24096811
TI  - Relation of video-head-impulse test and caloric irrigation: a study on the
      recovery in unilateral vestibular neuritis.
AB  - The head-impulse test (HIT) is an important test for examining unilateral
      vestibular hypofunction. The new video-head-impulse test (vHIT) is more sensitive
      and specific than the clinical bedside-head-impulse test. Alternatively, one can
      test for vestibular hypofunction with the caloric irrigation test. Various
      studies have shown that both tests may not always identify vestibular
      hypofunction; instead, the results of the tests might be contradictory. To
      further explore the question, of whether vHIT and caloric irrigation test the
      same part of the angular horizontal vestibulo-ocular reflex (VOR), we examined
      patients with unilateral vestibular neuritis at different points in time. The
      tonic vestibular imbalance (e.g., subjective-visual-vertical, ocular torsion and
      spontaneous nystagmus) and dynamic dysfunction of VOR (vHIT and bithermal caloric
      irrigation) were measured and quantified. While parameters of the tonic
      vestibular imbalance were well described by single exponential decay functions,
      dynamic parameters were less well defined. Therefore, to better compare the time
      course of pairs of two different parameters, we used a linear regression
      analysis. No linear correlation was found in the group and individually for the
      gain asymmetry and the ipsilesional gain of the vHIT with the unilateral weakness
      of the bithermal caloric irrigation tests. Linear correlation was found for most
      parameters of tonic vestibular imbalance. These findings are further evidence
      that vHIT and caloric irrigation test different parts of the angular VOR. 

PMID- 24096812
TI  - Are computed tomography and densitometric measurements useful in otosclerosis
      with mixed hearing loss? A retrospective clinical study.
AB  - The objective of the study was to investigate the relationship between extent of
      otosclerotic foci and audiological findings in otosclerotic patients with mixed
      hearing loss using high-resolution computed tomography (HRCT) and also to measure
      the density of bony labyrinth in otosclerotic patients and compared with control
      group. This was a retrospective study. Twenty-five patients with clinical
      otosclerosis and mixed hearing loss were included in the study. The average
      threshold of air-bone conductions (AC, BC) within the 0.5-4 kHz frequency range,
      and average air bone gap (ABG) were calculated. Eleven patients with normal HRCT
      who received cochlear implant were included in the study as the control group.
      The lesions in HRCT were staged according to their extension. Eight different
      points of the otic capsule in each patient were measured using HRCT. Fifty ears
      total, from 25 patients, had bilateral otosclerosis. The mean AC of all the ears
      was 63 dB, mean BC was 35.2 dB, and mean ABG was 27.8 dB. HRCT staging indicated
      22 ears had Grade 1, 21 ears had Grade 2, and 7 ears had Grade 3 lesions. There
      was a statistically significant difference between the mean AC, BC of ears with
      Grade 1 and Grade 2 when compared with the mean AC, BC of ears with Grade 3. When
      comparing the densitometric measurements of fissula ante fenestram localizations,
      a statistically significant difference was observed. HRCT examination and
      densitometric measurements in otosclerotic patients with mixed hearing loss
      presented significant results. We were unable to show a significant relationship
      between early stage and hearing thresholds, but there was a significant
      relationship in advanced stage. Densitometric measurements may provide
      significant results for otosclerosis, particularly for the FAF region when
      comparing with control group.

PMID- 24096813
TI  - Relationship between behavioral hearing thresholds and estimated auditory steady
      state response thresholds in children with a history of neonatal
      hyperbilirubinemia.
AB  - Increased serum bilirubin levels during infancy increase the risk of hearing loss
      in infants. This study aimed to investigate the relationship between pure-tone
      audiometry hearing thresholds and thresholds estimated using auditory steady
      state responses (ASSRs) in children with a history of neonatal
      hyperbilirubinemia, and to evaluate the usefulness of 90-Hz ASSR in estimating
      hearing thresholds in children. This study was conducted on 26 children (13 girls
      and 13 boys) who were aged 2.4-11 years and had a history of neonatal
      hyperbilirubinemia (bilirubin level >17 mg/dL). ASSR thresholds were compared
      with behavioral thresholds and were interpreted after considering the amount and
      type of hearing loss. Of the 26 children, 12 had normal hearing thresholds, and
      14 had varying degrees of sensorineural hearing loss. In general, a high
      correlation (r >= 0.81, p < 0.01) was found between the ASSR and behavioral
      thresholds. The highest correlation was observed at 2,000 Hz (r = 0.88, p <
      0.01). No significant difference was observed (p > 0.13) between mean behavioral
      and ASSR thresholds at 52 studied ears. The results of this study showed that 90
      Hz ASSR assessments provide reliable estimates of behavioral hearing thresholds
      in children who have a history of neonatal hyperbilirubinemia and sensorineural
      hearing loss or normal hearing.

PMID- 24096814
TI  - Management of major post-cochlear implant wound infections.
AB  - In post-cochlear implant (CI) wound infections, a commonly asked question is
      whether the device could be salvaged and if so, what the challenges were. The aim
      of this article is to study patients with major post-CI wound infections,
      identify the risk factors and discuss the management. The case records all CI
      recipients who developed post-CI wound infections that required parenteral
      antibiotics treatment or any form of surgery between Jan 1997 and Dec 2011 were
      retrospectively reviewed. Among the 432 CI surgeries performed by the senior
      author, 7 developed major post-CI wound infection (1.62 %). In children, the
      commonest etiology was from stitch abscesses. In four out of the five children
      who developed stitch abscesses, four were due to the use of non-absorbable
      polypropylene sutures, a technique which had since been discontinued. In adults,
      the cause was due to the late effects of prior radiotherapy for head and neck
      tumors. The commonest organism isolated from wound cultures was Staphylococcus
      aureus. Salvage surgery (complemented by antibiotics) was attempted in six out of
      eight patients managed. All were successfully salvaged with surgery entailing
      either skin flap reconstruction (2 patients), transposition of the CI body to new
      location (1 patient) or both (3 patients). Skin flap reconstruction surgery alone
      failed to control the infection in patients with a negative culture result and
      needed a subsequent transposition surgery of the device. Device transposition
      surgery was a consistently effective therapeutic approach, but carried a higher
      risk of iatrogenic damage to the electrode array as it might be embedded in new
      bone.

PMID- 24096815
TI  - Evaluation of functional results of CWD surgery with ossicular replacement
      prosthesis due to cholesteatoma using computed tomography.
AB  - With the use of high-resolution computed tomography, this retrospective clinical
      study evaluated the factors affecting hearing in patients who were operated on
      due to chronic otitis media with cholesteatoma and underwent ossiculoplasty with
      titanium total ossicular replacement prosthesis (TORP). Fifteen patients with
      postoperative hearing results of 20 dB or less air-bone gap, and thirteen
      patients with postoperative hearing results of 21 dB or more air-bone gap were
      the subjects of this study. All patients were operated on due to chronic otitis
      media and underwent ossiculoplasty with titanium TORP. High-Resolution Computed
      Tomography (HRCT) and pure-tone audiometry were performed on each patient after
      an average of 17 months, postoperatively. Three-dimensional oblique CT cross
      sections were analyzed with Vitrea 2((r)) software. The presence of soft tissue
      in the middle ear and contact between the prosthesis head plate and the bone had
      an adverse effect on hearing (p < 0.05). The angle between the TORP and the oval
      window did not seem to affect the hearing results (p > 0.05). The study results
      indicate that an examination of the patients with poor postoperative hearing with
      HRCT may help find the possible cause and allow for the determination of the
      prosthesis location.

PMID- 24096816
TI  - The impact of ankylosing spondylitis on audiovestibular functions.
AB  - In this study, we aimed to evaluate the audiovestibular functions in the patients
      with ankylosing spondylitis (AS). This prospective study was performed in
      collaboration by the Otolaryngology and Rheumatology Departments of Bozok
      University School of Medicine between May 1, 2012, and January 1, 2013. We
      studied 80 subjects consisting of 40 AS patients (37 men and 3 women) in whom the
      diagnosis confirmed by the criteria of New York and 40 healthy controls (35 men
      and 5 women). All participants were evaluated by routine audiologic (including
      tympanometric evaluation, pure-tone audiograms, speech tests) and vestibular
      studies (including spontaneous nystagmus, gaze, optokinetic, saccadic movements,
      smooth pursuit, caloric test and Dix-Hallpike tests). The tympanometric values
      did not show a statistically significant difference between the AS group and the
      healthy subjects (p > 0.05). At low frequencies (250, 500, 1,000, and 2,000 Hz)
      pure-tone audiologic evaluations also proved statistically non-significant
      results at mean air conduction thresholds (ACT) and bone conduction thresholds
      (BCT) between the AS and control groups (p > 0.05). At high frequencies (4,000,
      6,000, and 8,000 Hz), the ACTs and BCTs in AS group were lower than control group
      which was statistically significant (p < 0.05). The results of spontaneous
      nystagmus, gaze, optokinetic, canal paresis and saccadic movement tests between
      the two groups were statistically insignificant (p > 0.05). The comparison of
      smooth pursuit and Dix-Hallpike tests reached statistical significance (p <
      0.05). Videonystagmographic test (VNG) revealed central abnormalities in 7
      patients (17.5 %), peripheral abnormalities in 16 patients (40 %), and mixed
      abnormalities in 3 patients (7.5 %). Our findings suggest a possible association
      between AS and audiovestibular system dysfunction. We assume that the hearing and
      vestibular disturbances in AS are more prevalent than previously recognized.

PMID- 24096817
TI  - Chlamydophila pneumoniae and Mycoplasma pneumoniae were not identified in sinus
      mucosa of patients with chronic rhinosinusitis.
AB  - Chronic rhinosinusitis is a symptomatic inflammation of the mucosa of the nose
      and paranasal sinuses lasting for at least 12 weeks. Atypical bacteria
      Chlamydophila pneumoniae and Mycoplasma pneumoniae are important causes of human
      respiratory tract infection. Also, they were identified in bronchial respiratory
      epithelium of patients with chronic obstructive pulmonary disease or asthma.
      Having in mind the unified airway concept, it is also possible that these
      bacteria can cause persistent infection of sinus mucosa in patients with chronic
      rhinosinusitis. Sixty consecutive patients with chronic rhinosinusitis who
      underwent the functional endoscopic sinus surgery due to medical therapy failure
      were included in the study. During the operation, sinuses were irrigated with
      sterile 0.9% NaCl solution and this lavage was immediately aspirated. Aspirates
      were used for the detection of C. pneumoniae and M. pneumoniae DNA using real
      time PCR. C. pneumoniae and M. pneumoniae DNA were not detected in samples
      analysed. Atypical bacteria C. pneumoniae and M. pneumoniae did not cause
      persistent infection of sinus mucosa in patients with chronic rhinosinusitis.

PMID- 24096818
TI  - Cochlear implantation for single-sided deafness: the outcomes. An evidence-based
      approach.
AB  - The aim of the present paper is to critically review the current evidence on the
      efficacy of cochlear implantation as a treatment modality for single-sided
      deafness (SSD), and/or unilateral tinnitus. Systematic literature review in
      Medline and other database sources was conducted along with critical analysis of
      pooled data. The study selection includes prospective and retrospective
      comparative studies, case series and case reports. The total number of analyzed
      studies was 17. A total of 108 patients with SSD have been implanted; 66 patients
      due to problems associated with SSD, and 42 primarily because of debilitating
      tinnitus. Cochlear implantation in SSD leads to improved sound localization
      performance and speech perception in noise from the ipsilateral side with an
      angle of coverage up to (but not including) 90( degrees ) to the front, when
      noise is present in the contralateral quartile (Strength of recommendation B).
      Speech and spatial hearing also subjectively improve following the insertion of a
      cochlear implant (Strength of recommendation B); this was not the case regarding
      the quality of hearing. Tinnitus improvement was also reported following implant
      placement (Strength of recommendation B); however, patients need to be advised
      that the suppression is mainly successful when the implant is activated. The
      overall quality of the available evidence supports a wider use of cochlear
      implantation in SSD following appropriate selection and counseling (overall
      strength of recommendation B). It remains to be seen if the long-term follow-up
      of large number of patients in well conducted high quality studies will confirm
      the above mentioned results.

PMID- 24096819
TI  - Olfactory training for patients with olfactory loss after upper respiratory tract
      infections.
AB  - Olfactory training consisting of daily suprathreshold odor exposure over 12 weeks
      seems to improve olfactory function. It is unknown if a longer period of training
      might be more effective. A prospective non-randomized clinical study was
      performed including 39 patients with olfactory loss after an upper respiratory
      tract infection (URTI) of less than 24 months duration. Patients exposed
      themselves with suprathreshold concentrations of four odors (rose, eucalyptus,
      lemon, cloves) applied in ''Sniffin' Sticks'' felt-tip pens over 32 weeks.
      Olfactory function was performed before (T1), after 16 weeks (T2), and 32 weeks
      of training (T3) using the 'the Sniffin' Sticks test kit calculating the TDI
      score (Threshold, Discrimination, Identification). The mean TDI score showed a
      non-significant trend of improvement at T2, and was significantly increased at T3
      (p = 0.021). Overall, 31 patients (79%) showed an increased TDI score at T3. The
      increase of TDI from T1 to T3 was 4.6 +/- 5.1. Age, gender, duration and initial
      severity of olfactory loss had no influence on the improvement (all p > 0.05).
      Only patients with a D score lower than the median value of 8 showed a
      significantly higher increase of the D score at T3 (p = 0.004). The present study
      confirmed that olfactory training improves olfactory function in patients with
      olfactory loss after URTI. A longer duration of training over 32 weeks seems to
      increase the effectiveness in comparison to a 12-week period. This was tested in
      a completed German multicenter trial to be published soon containing a control
      group to include the effect of a spontaneous recovery after URTI.

PMID- 24096820
TI  - In vitro-in vivo evaluation of in situ gelling and thermosensitive ketoprofen
      liquid suppositories.
AB  - The main objective of this study was to investigate the release and
      pharmacokinetic profiles of ketoprofen (KP) from developed thermosensitive and
      mucoadhesive liquid suppositories. Thermosensitive liquid suppositories were
      prepared using KP, poloxamer 407 (P 407), poloxamer 188 (P 188) and various
      amounts of different mucoadhesive polymers. In vitro release studies was
      monitored by the USP XXVI paddle method. The results thus obtained were evaluated
      kinetically and mechanism of release was analyzed. Identification of poloxamer
      gel localization in vivo was conducted using white male rabbits by adding 1 %
      methylene blue. For in vivo studies, twenty-four white male rabbits were randomly
      divided into three groups. The rabbits in each group were administered with
      liquid suppository F1 [P407/P188/KP (4/20/2.5 %)], F5 [P407/P188/KP/C
      (4/20/2.5/0.8 %)] or conventional suppository (F-C) into the rectum. The plasma
      concentration of KP was analyzed by high performance liquid chromatography
      (HPLC). C max, AUC, MRT and T max were evaluated. The release of KP was variously
      affected by the mucoadhesive polymers. In vitro release studies showed that
      Carbopol 934 P(C) has significant effect on release rate among the mucoadhesive
      polymers. When the formulations were evaluated kinetically, different kinetic
      models were obtained. Formulation F6 [P407/P188/KP/C (4/20/2.5/1.6 %)] which
      contains the highest C concentration and very high viscosity, shows a
      significantly better fit with Higuchi kinetic model. n value of this formulation
      was also found approximately 0.5. n exponent results of the other formulations
      showed that KP might be released from the suppositories by non-Fickian diffusion.
      Identification of poloxamer gel localization in vivo showed that the
      suppositories remain in the rectum without leakage after administration. With
      regard to the results of in vivo studies, the AUC6->14 values of KP in liquid
      suppository containing C are significantly higher than those in liquid
      suppository without C. MRT0->24 and MRT0->infinity values of liquid suppository
      containing C are significantly higher than those in liquid suppository without C
      and conventional suppository. Conventional suppository and liquid suppository
      without C significantly gave faster time to reach the maximum plasma
      concentrations of KP. With regard to the in vitro and in vivo experiments, liquid
      suppository formulation F5 might be a promising formulation for the development
      of an effective rectal dosage form. 

PMID- 24096821
TI  - Tomato yellow leaf curl virus alters the host preferences of its vector Bemisia
      tabaci.
AB  - Bemisia tabaci, the whitefly vector of Tomato yellow leaf curl virus (TYLCV),
      seriously reduces tomato production and quality. Here, we report the first
      evidence that infection by TYLCV alters the host preferences of invasive B.
      tabaci B (Middle East-Minor Asia 1) and Q (Mediterranean genetic group), in which
      TYLCV-free B. tabaci Q preferred to settle on TYLCV-infected tomato plants over
      healthy ones. TYLCV-free B. tabaci B, however, preferred healthy tomato plants to
      TYLCV-infected plants. In contrast, TYLCV-infected B. tabaci, either B or Q, did
      not exhibit a preference between TYLCV-infected and TYLCV-free tomato plants.
      Based on gas chromatography-mass spectrometry (GCMS)analysis of plant terpene
      volatiles, significantly more beta-myrcene, thymene, beta-phellandrene,
      caryophyllene, (+)-4-carene, and alpha-humulene were released from the TYLCV-free
      tomato plants than from the TYLCV-infected ones. The results indicate TYLCV can
      alter the host preferences of its vector Bemisia tabaci B and Q. 

PMID- 24096822
TI  - Efficacy of deferred dosing of granulocyte colony-stimulating factor in
      autologous hematopoietic transplantation for multiple myeloma.
AB  - Routine administration of G-CSF following autologous hematopoietic SCT (ASCT)
      expedites ANC recovery and reduces hospitalization by 1-2 days; it has no impact
      on febrile neutropenia, infections, morbidity, mortality, event-free survival or
      OS. To determine whether delayed G-CSF dosage could result in equivalent ANC
      recovery and thereby improve cost effectiveness, we deferred the administration
      of G-CSF until WBC recovery had begun. A total of 117 patients with multiple
      myeloma received ASCT from January 2005 to September 2012. Of these, 52 were in
      the conventional dosing group (CGD) and received G-CSF from Day +7 for a median
      of five doses. In the deferred dosing group (DGD), 65 patients received G-CSF
      from median day 14 post transplant for a median of zero doses. There was no
      difference between groups in the incidence or duration of febrile neutropenia,
      duration of ?grade III mucositis, weight gain, rash, engraftment syndrome or
      early death (100 days). The DGD group had a significantly longer time to
      neutrophil engraftment than the CGD group (15 days vs 12 days; P<0.0001), a
      longer period of severe neutropenia (<100/MUL; 8 days vs 6 days; P<0.0001),
      longer treatment with intravenous antibiotics (7 days vs 5 days; P=0.016) and
      longer hospital stay (19 days vs 17 days; P=<0.0001). Although the cost of G-CSF
      was lower in the DGD group (mean $308 vs $2467), the additional hospitalization
      raised the median total cost of ASCT in this group by 17%. There was, however, no
      adverse effect of deferred dosing on the rate of febrile neuropenic episodes or
      Day 100 survival, so that deferred dosing of G-CSF may be suitable for patients
      receiving ASCT as outpatients, for whom longer hospital stay would not be an
      offsetting cost. 

PMID- 24096823
TI  - Application of machine learning algorithms for clinical predictive modeling: a
      data-mining approach in SCT.
AB  - Data collected from hematopoietic SCT (HSCT) centers are becoming more abundant
      and complex owing to the formation of organized registries and incorporation of
      biological data. Typically, conventional statistical methods are used for the
      development of outcome prediction models and risk scores. However, these analyses
      carry inherent properties limiting their ability to cope with large data sets
      with multiple variables and samples. Machine learning (ML), a field stemming from
      artificial intelligence, is part of a wider approach for data analysis termed
      data mining (DM). It enables prediction in complex data scenarios, familiar to
      practitioners and researchers. Technological and commercial applications are all
      around us, gradually entering clinical research. In the following review, we
      would like to expose hematologists and stem cell transplanters to the concepts,
      clinical applications, strengths and limitations of such methods and discuss
      current research in HSCT. The aim of this review is to encourage utilization of
      the ML and DM techniques in the field of HSCT, including prediction of
      transplantation outcome and donor selection. 

PMID- 24096824
TI  - Six-month freedom from treatment failure is an important end point for acute GVHD
      clinical trials.
AB  - We studied the American Society for Blood and Marrow Transplantation (ASBMT) 6
      month (m) freedom from treatment failure (FFTF) as a predictor of survival for
      patients with acute GVHD (aGVHD) requiring treatment. Adult patients undergoing
      allogeneic hematopoietic cell transplant (HCT) from February 2007 to March 2009
      who were enrolled in a prospective biomarker clinical trial and developed aGVHD
      requiring systemic corticosteroids by day +100 were included (N=44). Six-month
      FFTF was defined as per the ASBMT guidelines (absence of death, malignancy
      relapse/progression or systemic immunosuppression change within 6 months of
      starting steroids and before chronic GVHD development). aGVHD was treated with
      systemic corticosteroids in 44 patients. Day 28 response after steroid initiation
      (complete response+very good partial response+partial response) occurred in 38
      (87%) patients, but only 28 (64%) HCT recipients met the 6-m FFTF end point. Day
      28 response predicted 6-m FFTF. Achieving 6-m FFTF was associated with improved 2
      year (y) OS (81% vs 48%; P=0.03) and decreased 2-y non-relapse mortality (8% vs
      49%; P=0.01). In multivariate analysis, 6-m FFTF continued to predict improved OS
      (hazard ratio, 0.27; P=0.03). The 6-m FFTF end point measures fixed outcomes,
      predicts long-term therapeutic success and could be less prone to measurement
      error than aGVHD clinical response at day 28. 

PMID- 24096825
TI  - Distress, problems and supportive care needs of patients treated with auto- or
      allo-SCT.
AB  - Hematological malignancies and treatment with hematopoietic SCT are known to
      affect patients' quality of life. The problem profile and care needs of this
      patient group need clarification, however. This study aimed to assess distress,
      problems and care needs after allo- or auto-SCT, and to identify risk factors for
      distress, problems or care needs. In this cross-sectional study, patients treated
      with allo-SCT or auto-SCT for hematological malignancies completed the Distress
      Thermometer and Problem List. Three patient groups were created: 0-1, 1-2.5 and
      2.5-5.5 years after transplantation. After allo-SCT, distress and the number of
      problems tended to be lower with longer follow-up. After auto-SCT, distress was
      highest at 1-2.5 year(s). Patients mainly reported physical problems, followed by
      cognitive-emotional and practical problems. A minority reported care needs. Risk
      factors for distress as well as problems after allo-SCT included younger age,
      shorter time after transplantation and GVHD. A risk factor for distress as well
      as problems after auto-SCT was the presence of comorbid diseases. Up to 5 years
      after auto-SCT or allo-SCT, patients continue to experience distress and
      problems. Judged by prevalence, physical problems are first priority in
      supportive care, followed by cognitive-emotional and practical problems. 

PMID- 24096826
TI  - Activated protein C inhibits proliferation and tumor necrosis factor alpha
      stimulated activation of p38, c-Jun NH2-terminal kinase (JNK) and Akt in
      rheumatoid synovial fibroblasts.
AB  - Synovial fibroblast proliferation is a hallmark of the invasive pannus in the
      rheumatoid joint. Activated protein C (APC) is a natural anticoagulant that
      exerts antiinflammatory and cyto-protective effects in various diseases via
      endothelial protein C receptor (EPCR) and proteinase-activated receptor (PAR)
      mediated pathways. In this study, we investigated the effect and the underlying
      cellular signaling mechanisms of APC on proliferation of human rheumatoid
      synovial fibroblasts (RSFs). We found that APC stimulated proliferation of mouse
      dermal fibroblasts (MDFs) and normal human dermal fibroblasts (HDFs) by up to
      60%, but robustly downregulated proliferation of RSFs. APC induced the
      phosphorylation of extracellular signal-regulated protein kinase (ERK) and
      enhanced expression of p21 and p27 in a dose-dependent manner in RSFs. The latter
      effect was inhibited by pre-treatment with the ERK inhibitors PD98059 and U0126
      but not by p38 inhibitor SB203580. In addition, APC significantly downregulated
      tumor necrosis factor (TNF)alpha-stimulated cell proliferation and activation of
      p38, c-Jun NH2-terminal kinase (JNK) and Akt in RSFs. These results provide the
      first evidence that APC selectively inhibits proliferation and the inflammatory
      signaling pathways of RSFs. Thus, APC may reduce synovial hyperplasia and pannus
      invasion in rheumatoid arthritis. 

PMID- 24096827
TI  - Connexin40 regulates platelet function.
AB  - The presence of multiple connexins was recently demonstrated in platelets, with
      notable expression of Cx37. Studies with Cx37-deficient mice and connexin
      inhibitors established roles for hemichannels and gap junctions in platelet
      function. It was uncertain, however, whether Cx37 functions alone or in
      collaboration with other family members through heteromeric interactions in
      regulation of platelet function. Here we report the presence and functions of an
      additional platelet connexin, Cx40. Inhibition of Cx40 in human platelets or its
      deletion in mice reduces platelet aggregation, fibrinogen binding, granule
      secretion and clot retraction. The effects of the Cx37 inhibitor (37,43)Gap27 on
      Cx40(-/-) mouse platelets and of the Cx40 inhibitor (40)Gap27 on Cx37(-/-) mouse
      platelets revealed that each connexin is able to function independently.
      Inhibition or deletion of Cx40 reduces haemostatic responses in mice, indicating
      the physiological importance of this protein in platelets. We conclude that
      multiple connexins are involved in regulating platelet function, thereby
      contributing to haemostasis and thrombosis.

PMID- 24096828
TI  - Intraperitoneal germ cell transplantation in the Nile tilapia Oreochromis
      niloticus.
AB  - Germ cell transplantation offers promising applications in finfish aquaculture
      and the preservation of endangered species. Here, we describe an intraperitoneal
      spermatogonia transplantation procedure in the Nile tilapia Oreochromis
      niloticus. Through histological analysis of early gonad development, we first
      determined the best suitable stage at which exogenous germ cells should be
      transplanted into the recipients. For the transplantation procedure, donor testes
      from a transgenic Nile tilapia strain carrying the medaka beta-actin/enhanced
      green fluorescent protein (EGFP) gene were subjected to enzymatic dissociation.
      These testicular cells were then stained with PKH26 and microinjected into the
      peritoneal cavity of the recipient fish. To confirm colonization of the donor
      derived germ cells, the recipient gonads were examined by fluorescent and
      confocal microscopy. PKH26-labeled cells exhibiting typical spermatogonial
      morphology were incorporated into the recipient gonads and were not rejected
      within 22 days posttransplantation. Long-term survival of transgenic donor
      derived germ cells was then verified in the gonads of 5-month-old recipients and
      in the milt and vitelogenic oocytes of 1-year-old recipients, by means of PCR
      using EGFP-specific primers. EGFP-positive milt from adult male recipients was
      used to fertilize non-transgenic oocytes and produced transgenic offspring
      expressing the donor-derived phenotype. These results imply that long-term
      survival, proliferation, and differentiation of the donor-derived spermatogonia
      into vitelogenic oocytes and functional spermatozoa are all possible. Upon
      further improvements in the transplantation efficiency, this intraperitoneal
      transplantation system could become a valuable tool in the conservation of
      genetic resources for cichlid species. 

PMID- 24096829
TI  - Anticonvulsant effects of Fuzi total alkaloid on pentylenetetrazole-induced
      seizure in mice.
AB  - We investigated the anticonvulsant effect of acute Fuzi total alkaloid (FTA) in
      seizure induced by the GABAA-receptor antagonist pentylenetetrazole (PTZ). FTA
      significantly increased the seizure latency and decreased the mortality in PTZ
      treated mice. Administration of PTZ increased c-Fos expression in the
      hippocampus, medial prefrontal cortex, and piriform cortex; and this PTZ-induced
      effect was inhibited by FTA in a dose-dependent manner. Furthermore, the effects
      of FTA on PTZ-induced seizure and c-Fos expression were reversed by the
      GABAA/benzodiazepine receptor-selective antagonist flumazenil. These findings
      suggest that the anticonvulsant effects of FTA may be related to modulation of
      GABAA-benzodiazepine receptor complex. 

PMID- 24096830
TI  - Effect of lamotrigine on Na(v)1.4 voltage-gated sodium channels.
AB  - Lamotrigine (LTG) is an anticonvulsant drug used in the treatment of epilepsy and
      bipolar disorder and it has been known that LTG targets voltage-dependent sodium
      channels (VGSCs). In this study, we investigated the effect of LTG on the Nav1.4
      Na(+) current using HEK293 cells expressing mouse Nav1.4 VGSCs. By the treatment
      of LTG, Nav1.4 Na(+) current was inhibited in a dose-dependent manner. Moreover,
      100 MUM LTG decreased Nav1.4 Na(+) current around 40% and shifted the V1/2 of the
      inactivation curve to the hyperpolarization side by 20.96 mV. These findings
      suggest that LTG inhibits Nav1.4 Na(+) current and modifies the kinetics of the
      inactivated state. 

PMID- 24096831
TI  - Significance of matrix metalloproteinase-9 inhibition by imidapril for prevention
      of abdominal aortic aneurysms in angiotensin II type 1 receptor-knockout mice.
AB  - To clarify the matrix metalloproteinase (MMP)-9 inhibitory effect of an
      angiotensin-converting enzyme (ACE) inhibitor in vivo, we evaluated the effect of
      an ACE inhibitor against elastase-induced abdominal aortic aneurysm (AAA)
      progression in mice. Molecular models showed that imidapril bound directly to the
      mouse MMP-9 active center. An active form of imidapril, imidaprilat, dose
      dependently inhibited MMP-9 activity in the extract from elastase-induced AAA in
      wild-type mice. Imidapril (10 mg/kg per day) was administered to wild-type or
      angiotensin II type 1 (AT1) receptor knockout mice. Blood pressure was
      significantly lower in AT1 receptor-knockout mice than in wild-type mice, but
      imidapril did not affect blood pressure in AT1 receptor-knockout mice. The aortic
      diameter was significantly expanded after elastase application, but the expansion
      was significantly lower in AT1 receptor-knockout mice than in wild-type mice. In
      AT1 receptor-knockout mice, the aortic expansion was further attenuated by
      imidapril. MMP-9 activity in aorta was significantly augmented after elastase
      application. The MMP-9 activity was significantly lower in AT1 receptor-knockout
      mice than in wild-type mice, and it was further attenuated by imidapril. In
      conclusion, MMP-9 inhibition by imidapril might contribute to the attenuation of
      AAA progression in AT1 receptor-knockout mice. 

PMID- 24096832
TI  - New screening system for selective blockers of voltage-gated K(+) channels using
      recombinant cell lines dying upon single action potential.
AB  - To develop a simple screening system for blockers of voltage-gated Kv1.3 and
      Kv1.5 channels, new cell lines co-expressing mutated Nav1.5 (IFM/Q3), Kir2.1
      (Kir), and Kv1.3 or Kv1.5 were introduced as IFM/Q3+Kir+Kv1.3 and
      IFM/Q3+Kir+Kv1.5, respectively. Electrical stimulation (ES) of a cell line,
      IFM/Q3+Kir, induced prolonged action potentials due to the slow inactivation of
      IFM/Q3 and subsequent cell death. Additional co-expression of Kv1.3 or Kv1.5 to
      IFM/Q3+Kir shortened the evoked action potentials and prevented cell death. In
      the presence of margatoxin, a selective Kv1.3-blocker, ES induced cell death in
      IFM/Q3+Kir+Kv1.3, but not in IFM/Q3+Kir+Kv1.5. In the presence of 4
      aminopyridine, a non-selective Kv-channel blocker, ES application elicited cell
      death in both cell lines. The IC50s of acacetin, a Kv1.5-blocker, was 10.2 MUM in
      IFM/Q3+Kir+Kv1.3 and almost identical to that in IFM/Q3+Kir+Kv1.5 (7.6 MUM). The
      IC50s of citalopram, a 5-HT uptake-inhibitor, were 1.8 MUM in IFM/Q3+Kir+Kv1.3
      and 1.5 MUM in IFM/Q3+Kir+Kv1.5, respectively. These IC50s were comparable to
      those determined electrophysiologically. In conclusion, acacetin and citalopram
      block both Kv1.3 and Kv1.5 without selectivity. The Kv1.3 or Kv1.5 channel
      inhibition assay using these new cell lines may be applicable to high-throughput
      screening because of its simplicity, accuracy, and high cost-performance. 

PMID- 24096833
TI  - Novel mouse model of combined hyperlipidemia associated with steatosis and liver
      injury by a single-dose intragastric administration of schisandrin
      B/cholesterol/bile salts mixture.
AB  - Hyperlipidemia is referred to as hypercholesterolemia, hypertriglyceridemia, or
      both in combined hyperlipidemia. Here, a novel mouse model of combined
      hyperlipidemia is described. Mice were orally given a single dose of a modeling
      agent (MA) made of a mixture of schisandrin B/cholesterol/bile salts (1/2/0.5
      g/kg) suspended in olive oil. MA treatment increased serum triglycerides (TG) and
      total cholesterol (TC) (up to 422% and 100% at 12 - 96 h post-treatment,
      respectively) and hepatic TG and TC (up to 220% and 26%, respectively) in a time-
      and dose-dependent manner, associated with elevation of high-density lipoprotein
      and low-density lipoprotein levels. Serum alanine/aspartate aminotransferase
      activities, indicators of liver cell damage, were also elevated (up to 198%) at
      48 and 72 h post-MA treatment. Fenofibrate blocks MA-induced hyperlipidemia,
      lipid accumulation in the liver, as well as liver injury. Oral administration of
      a mixture of schisandrin B, cholesterol, and bile salt could generate an
      interesting mouse model of combined hyperlipidemia associated with hepatic
      steatosis and steatohepatitis. 

PMID- 24096834
TI  - Serotonergic modulation of neuronal activity in the nucleus accumbens following
      repeated methamphetamine administration in rats.
AB  - Electrophysiological studies were performed to determine whether serotonergic
      modulation in the nucleus accumbens (NAcc) was affected after repeated
      methamphetamine (MAP) administration. NAcc slices (400 MUm) from Wistar rats
      administered MAP (5 mg/kg) or saline once daily for 5 days were prepared 1, 5, or
      10 days after the final injection. Population spikes (PS) induced by local
      stimulation of NAcc were recorded. PS inhibition by serotonin was significantly
      attenuated in the MAP group at 5 days but did not differ at 1 or 10 days. We next
      analyzed the effects of serotonin receptor subtype (5-HT1A,2,3,4,6,7)-selective
      agonists of PS. Differences between saline and MAP groups in 5-HT1A,2,3,4,6
      receptor agonist-induced changes of PS were small or not significant.
      Interestingly, 5-HT7 receptor agonists significantly enhanced PS in the MAP
      group. Changes in the secondary messenger system related to 5-HT7 receptors were
      also investigated. Adenylate cyclase activator-induced PS enhancements were
      significantly larger in the MAP group. However, dibutyryl-cAMP-induced PS
      enhancement was not significantly different. In conclusion, 5-HT-induced
      inhibition of PS in NAcc was attenuated 5 days after repeated MAP treatment: the
      change in the effect of 5-HT was probably due to enhancement of the excitatory
      modulation via the 5-HT7 receptor with adenylate cyclase signal transduction
      systems. 

PMID- 24096835
TI  - The (13)C-butyrate breath test: a new non-invasive method for assessing colitis
      in a murine model.
AB  - The conventional method for the real-time assessment of murine colitis requires a
      large number of animals. The (13)C-butyrate breath test could be useful for
      evaluating disease activity and the amelioration of human ulcerative colitis non
      invasively. The purpose of this study was to investigate whether this test can be
      used to assess the phase of inflammation in murine colitis. We investigated the
      excretion of (13)CO2 measured by the (13)C-butyrate breath test after rectal
      instillation of butyrate in the DSS colitis model. The colon length, MPO
      activity, and histological damage were analyzed as parameters. The efficacy of
      salicylazosulfa-pyridine (SASP) on (13)CO2 excretion was also studied. The
      (13)CO2 excretion curves in the 0.5% DSS- and 0.75% DSS-treated groups were
      significantly lower than those in the normal group (P < 0.01, P < 0.01). Good
      correlation between the results of the breath test and the inflammation
      parameters was observed. The (13)CO2 excretion curve in DSS murine colitis after
      the administration of SASP was significantly higher than in the normal group (P <
      0.01). The (13)C-butyrate breath test can be used to evaluate the inflammatory
      phase of DSS murine colitis, and it may be a new non-invasive method for
      assessing murine colitis. 

PMID- 24096836
TI  - Milnacipran inhibits itch-related responses in mice through the enhancement of
      noradrenergic transmission in the spinal cord.
AB  - We investigated whether milnacipran, a serotonin-noradrenaline reuptake
      inhibitor, exhibits an antipruritic effect through the spinal action in mice.
      Intrathecal injections of milnacipran (0.1 - 10 MUg/site) significantly
      suppressed serotonin-induced biting, which is an itch-related response. However,
      such an effect was not observed with fluvoxamine (10 MUg/site), which is a
      selective serotonin reuptake inhibitor. Furthermore, an intraperitoneal injection
      of milnacipran (10 mg/kg) inhibited serotonin-induced biting. When phentolamine
      (1.0 MUg/site), a non-selective alpha-adrenoceptor antagonist, was intrathecally
      injected, it inhibited the above response of milnacipran. These results suggest
      that milnacipran suppresses itching through the inhibition of noradrenaline
      reuptake in the spinal cord. 

PMID- 24096837
TI  - Ameliorative effects of thyme and calendula extracts alone or in combination
      against aflatoxins-induced oxidative stress and genotoxicity in rat liver.
AB  - The aims of the current work were to evaluate the hepatoprotective effect of
      calendula flowers and/or thyme leave extracts on aflatoxins (AFs)-induced
      oxidative stress, genotoxicity and alteration of p53 bax and bcl2 gene
      expressions. Eighty male Sprague-Dawley rats were divided into eight equal groups
      including: the control group, the group fed AFs-contaminated diet (2.5 mg/kg
      diet) for 5 weeks, the groups treated orally with thyme and/or calendula extract
      (0.5 g/kg b.w) for 6 weeks and the groups pretreated orally with thyme and/or
      calendula extract 1 week before and during AFs treatment for further 5 weeks.
      Blood, liver and bone marrow samples were collected for biochemical analysis,
      gene expression, DNA fragmentation and micronucleus assay. The results showed
      that AFs induced significant alterations in oxidative stress markers, increased
      serum AFP and inflammatory cytokine, percentage of DNA fragmentation, the
      expression of pro-apoptotic gene p53 and bax accompanied with a decrease in the
      expression of bcl2. Animals treated with the extracts 1 week before AFs treatment
      showed a significant decrease in oxidative damage markers, micronucleated cells,
      DNA fragmentation and modulation of the expression of pro-apoptotic genes. These
      results suggested that both calendula and thyme extracts had anti-genotoxic
      effects due to their higher content of total phenolic compounds. 

PMID- 24096839
TI  - Mission Kishore Uday, getting IAP ready to meet the challenge of adolescent
      health.

PMID- 24096838
TI  - Effect of strain on human dermal fibroblasts in a three-dimensional collagen
      sponge.
AB  - Our aim was to design a simple compression system and investigate the influence
      of mechanical stress on skin-like structures. Many mechanical compression studies
      have employed intricate culture systems, so the relationship between
      extracellular matrix material and the response of skin cells to mechanical stress
      remains unknown. Our approach uses only glass vials, 6-well plates and standard
      laboratory equipment. We examined the influence of mechanical stress on human
      skin fibroblasts embedded within a collagen sponge. The results show that
      mechanical compression increases MMP-1 and MMP-2 release by the cells into the
      the cell culture. Our results suggest that pressure on the skin may affect
      extracellular matrix degradation through some as yet unidentified pathways and
      that IL-6 mRNA expression may be involved in this effect. Using our approach, the
      effects of static mechanical stress on protein expression by cells in the culture
      medium and in sponges can be easily examined, and therefore this system will be
      useful for further analyses of skin responses to mechanical stress. 

PMID- 24096840
TI  - Genetic testing in children.
AB  - Increasing availability of DNA based tests in clinical practice has lead to
      widespread debate on the ethical issues involved. The wider usage of these tests
      in children has raised many questions regarding the ethics, validity of the
      request and its effects on childs psychosocial well-being. Though there have been
      much discussion with many studies attempting to address the issue, there is no
      consensus. Formulation of guidelines has been hampered by the diversity of tests
      available for varied indications and lack of research studying the effects of
      testing in children over a time. Some tests have valid indications with proven
      benefits over harms while others have less clear justification. We attempt to
      address this issue with the intent to sensitize the caregivers regarding various
      aspects to be considered before offering any genetic tests in children. 

PMID- 24096841
TI  - How cost-effective is facility-based newborn care in India?

PMID- 24096842
TI  - Follow-up studies - beyond survival.

PMID- 24096843
TI  - Relevance of measuring body fat in children.

PMID- 24096844
TI  - Reaching the heights: the journal during the editorship of Dr R K Puri (March
      1990-1994).

PMID- 24096845
TI  - Influenza vaccination in India: position paper of Indian Academy of Pediatrics,
      2013.
AB  - Burden of Influenza is significantly higher in developing countries as compared
      to developed countries, but the data on the disease burden is less well defined
      in most of the developing countries including India, and consequently,
      constraints evolving strategies for prioritization of measures to prevent and
      control it. The swine flu or A(H1N1) pandemic is on the wane but the virus
      continues to circulate causing sporadic outbreaks even in 2013. The A(H1N1)pdm09
      has replaced the previous circulating seasonal A (H1N1) virus and acquired the
      status of a seasonal virus. Limited influenza activity is usually seen throughout
      the year in India with a clear peaking during the rainy season. The rainy season
      in the country lasts from June to August in all the regions except Tamil Nadu
      where it occurs from October to December. IAP recommends the ideal time for
      offering influenza vaccines is just before the onset of rainy season. The
      efficacy/effectiveness data of trivalent inactivated influenza vaccines are also
      presented in different age groups and different categories of individuals. The
      IAP maintains its earlier recommendations of using the current trivalent
      inactivated influenza vaccine in all children with risk factors but not as a
      universal measure. IAP has now prioritized different target groups for influenza
      vaccination based on contribution of the group to the overall influenza burden,
      disease severity, and vaccine effectiveness in different age groups and
      categories. The current trivalent inactivated influenza vaccines incorporate the
      2009 pandemic strain also, hence avert the need of a separate A (H1N1) vaccine.
      IAP stresses the need of more refined surveillance; large scale studies on
      effectiveness of seasonal influenza vaccines in Indian children, and more
      effective, properly matched, higher-valent influenza vaccines. 

PMID- 24096846
TI  - Iodine deficiency disorders in school age children in Kullu District, Himachal
      Pradesh.
AB  - Iodine deficiency disorder is a major public health problem in Himachal Pradesh.
      A study was conducted in district Kullu to assess the prevalence of IDD in school
      age children. Clinical examination of the thyroid of 1986 children was conducted.
      On the spot urine and salt samples were collected. The Total Goiter Rate was
      found to be 23.4% and median urinary iodine excretion was 175 ug/L. The
      population is possibly in transition phase from iodine deficient to iodine
      sufficient nutrition.

PMID- 24096847
TI  - Treatable cause of ventricular dysfunction in DiGeorge syndrome.

PMID- 24096848
TI  - Splenic infarction in P.vivax malaria.

PMID- 24096849
TI  - Systemic lupus erythematosus in children: the Indian story.

PMID- 24096850
TI  - authors reply: Primary neonatal psoas abscess.

PMID- 24096851
TI  - Disulfiram poisoning causing acute encephalopathy.

PMID- 24096852
TI  - Waist circumference: diagnostic tool for health risk in children.

PMID- 24096853
TI  - Fulminant Epstein Barr virus encephalitis - can it be due to X linked
      lymphoproliferative disease.

PMID- 24096854
TI  - "Illuminating" - early diagnosis of intestinal perforation in a neonate.

PMID- 24096855
TI  - Bullous dermatitis artefacta.

PMID- 24096856
TI  - Immunoglobulin G4-related disease associated with cutaneous vasculitis.

PMID- 24096857
TI  - Extracellular biosynthesis of silver nanoparticles: effects of shape-directing
      cetyltrimethylammonium bromide, pH, sunlight and additives.
AB  - The work reported in this paper describes the preparation, morphology, stability
      and sensitivity of Ag-nanoparticles towards sunlight using Allium sativum, garlic
      extract for the first time. The synthesized silver particles show an intense
      surface plasmon resonance band in the visible region at 410 nm. The position of
      the wavelength maxima, blue and red shift, strongly depends on the sunlight and
      pH. TEM analysis revealed the presence of spherical, different size (from 5.0 to
      30 nm) and garlic constituents bio-conjugated, stabilized and/or layered silver
      nanoparticles. The concentrations of garlic extract, cetyltrimethylammonium
      bromide, Ag(+) ions and reaction time play vital roles for nucleus formation and
      the growth processes. Sulfur-containing biomolecules of extract, especially
      cysteine, are responsible for the reduction of Ag(+) ions into metallic Ag(0).
      The agglomeration number of the silver nanoparticles (N Ag) and the average
      number of free electrons per particle (n fe) are calculated and discussed. 

PMID- 24096858
TI  - Haemocompatibility assessment of synthesised platinum nanoparticles and its
      implication in biology.
AB  - The growing need for advanced treatment of evolving diseases has become a
      motivation for this study. Among the noble metals, platinum nanoparticles are of
      importance because of their catalytic property, antioxidant potential, minimal
      toxicity and diverse applications. Biological process of synthesis has retained
      its significance, because it is a simple one-step process yielding stable
      nanoparticles. Herein, we have synthesised platinum nanoparticles through a green
      process using the unexplored seaweed Padina gymnospora, a brown alga. The course
      of synthesis was monitored and the nanoparticles were characterised using UV
      visible spectroscopy. The synthesised nanoparticles were studied using TEM, XRD
      and FTIR. The TEM and XRD studies reveal the size of the nanoparticle to be <35
      nm. The catalytic nanoparticles were capable of oxidising NADH to NAD(+). The
      biocompatibility was tested by haemolytic assay for the furtherance of the
      application of platinum nanoparticles in medicine. This is the first report on
      the biogenic synthesis of platinum nanoparticles using seaweed.

PMID- 24096859
TI  - Duplication of radiology imaging studies in the emergency department: what is the
      cost?
AB  - OBJECTIVE: To quantify the rate of preventable duplication of imaging studies in
      the Emergency Department. Previously, to estimate potential savings from the
      Health Information Exchange, figures used to be based on expert opinion, as the
      actual rate of redundant imaging is unknown. MATERIALS AND METHODS: We
      prospectively quantified the frequency of duplicate CT scans in tertiary care and
      community hospital emergency departments (ED) through a short questionnaire at
      the time the studies were ordered. RESULTS: During the study period, 9246 CT
      scans were performed with a preventable duplicate rate of 0.42%. Both sites had
      equivalent rates of preventable duplicates. DISCUSSION AND CONCLUSIONS: We used
      two EDs to quantify the rate of preventable duplicate CT scans ordered. Our
      results demonstrate that only 0.4% of CT scans performed in our EDs are
      preventable duplicates. Our rate of preventable duplicate studies was much lower
      than what experts and emergency practitioners suspected, which suggests that
      potential cost savings from elimination of preventable duplicates may also be
      much lower than currently estimated.

PMID- 24096860
TI  - What is important to patients in wound management.
AB  - Traumatic wounds are a common reason for patients to attend emergency
      departments. There are many ways of managing these wounds from glue to suturing.
      The authors conducted a patient survey to identify the outcome measures most
      important to patients after closure of traumatic wounds. The results showed that
      having the least chance of infection was the most important outcome, followed by
      being looked after by caring staff and a quick recovery. These finding were
      consistent regardless of the anatomical location of the wound or age of the
      patient. This information is being used to guide the authors in the most
      appropriate outcome measures for further research. 

PMID- 24096861
TI  - Sequence dependent lipid-mediated effects modulate the dimerization of ErbB2 and
      its associative mutants.
AB  - The association of transmembrane helices is an important event in several
      biological processes, but the factors governing association, especially the non
      specific environmental effects, have still not been elucidated. Here, we use
      coarse-grain molecular dynamics simulations to study the association of ErbB2
      transmembrane helices and three "oncogenic mutants." Self-assembly simulations
      and the dimerization free-energy profiles confirm an energetically-favorable
      dimerized state for both the wildtype and the mutants. The dissociation free
      energy of all three mutants is calculated to be larger than the wildtype peptide.
      Along with favourable protein-protein interactions, non-specific environmental
      effects are observed to contribute to the association. In particular, local
      bilayer thinning along with membrane perturbations are seen around the mutants.
      The membrane perturbations are reduced upon helix association, suggesting that
      lipid chain packing is an important driving force for helix dimerization. Our
      results highlight the importance of both specific as well as non-specific driving
      forces in the association of transmembrane helices. 

PMID- 24096862
TI  - Better together: reduced compliance after sequential versus simultaneous
      bilateral hearing aids fitting.
AB  - PURPOSE: The purpose of this study was to determine the effects of sequential
      versus simultaneous bilateral hearing aids fitting on patient compliance. METHOD:
      Thirty-six older adults with hearing impairment participated in this study.
      Twelve were fitted with bilateral hearing aids simultaneously. The remaining
      participants were fitted sequentially: One hearing aid (to the left or to the
      right ear) was used initially; 1 month later, the other ear was also fitted with
      a hearing aid for bilateral use. Self-reports on usefulness and compliance were
      elicited after the first and second months of hearing aid use. In addition, the
      number of hours the hearing aids were used was extracted from the data loggings
      of each device. RESULTS: Simultaneous fitting resulted in high levels of
      compliance and consistent usage throughout the study period. Sequential fitting
      resulted in abrupt reduction in compliance and hours of use once the second
      hearing aid was added, both in the clinical scoring and in the data loggings.
      CONCLUSIONS: Simultaneous fitting of bilateral hearing aids results in better
      compliance compared with sequential fitting. The addition of a second hearing aid
      after a relatively short period of monaural use may lead to inconsistent use of
      both hearing aids.

PMID- 24096863
TI  - Noise levels among spectators at an intercollegiate sporting event.
AB  - PURPOSE: The intensity of noise levels in a basketball arena during games, as
      well as the hearing sensitivity of attendees, was measured for the purpose of
      assessing the impact of the noise on hearing thresholds. METHOD: Noise levels at
      10 intercollegiate basketball games were measured with a dosimeter affixed on the
      shoulders of attendees. Hearing thresholds and distortion product otoacoustic
      emissions were measured for 20 participants just before attending a basketball
      game and within an hour of the end of the game to determine whether changes in
      hearing thresholds resulted from exposure to the sound levels within the arena
      during the games. RESULTS: Participants demonstrated temporary shifts in pure
      tone thresholds and reductions in the intensity of their otoacoustic emissions
      after attendance at 1 of the basketball games. Dosimeter measurements showed that
      noise at 6 of the 10 basketball games exceeded acceptable intensity levels when
      compared with a national workplace noise exposure standard. CONCLUSION: Although
      noise intensities, on average, did not exceed workplace exposure standards,
      universities would be wise to be proactive in warning spectators about the
      potential dangers of noise exposure at sporting events, make earplugs available
      to interested spectators, and implement a hearing conservation program for
      employees working in noise.

PMID- 24096864
TI  - The creation of a comprehensive and a brief core set for hearing loss using the
      international classification of functioning, disability and health.
AB  - PURPOSE: In May 2001, to integrate biological, psychological, and social aspects
      of human functioning, the World Health Assembly endorsed the International
      Classification of Functioning, Disability and Health (ICF). The aim of this
      article is to describe the creation of Comprehensive and Brief ICF Core Sets for
      Hearing Loss. The core sets consist of the most relevant ICF categories for
      hearing loss. METHOD AND RESULTS: Four preparatory studies were carried out and
      presented at a consensus conference, resulting in a Comprehensive ICF Core Set
      for Hearing Loss, consisting of 117 ICF categories, and a Brief ICF Core Set for
      Hearing Loss, consisting of 27 categories (of the 117). CONCLUSION: The
      Comprehensive ICF Core Set for Hearing Loss can be a user-friendly tool for
      conducting comprehensive, multidisciplinary assessments. The Brief ICF Core Set
      can be used for many purposes, such as research and population studies. However,
      its most common use is by individuals seeking to provide a brief description and
      assessment of functioning of a person with hearing loss.

PMID- 24096865
TI  - Semi-structured listening experience (listening training) in hearing aid fitting:
      influence on dichotic listening.
AB  - PURPOSE: In this study, the authors tested whether training with amplified, clear
      speech in regular room acoustics would result in larger perceptual gains of
      auditory processing in elderly hearing aid users. METHOD: Elderly participants
      with hearing impairment (N = 36, ages 64-88) were fitted with bilateral hearing
      aids and were randomly assigned to 2 unequal groups. Study group participants
      were provided with 7 sessions (1 month) of individual listening training during
      which a free conversation was conducted, with the aim of stimulating the
      amplified ears with verbal auditory input. The control group participants were
      fitted with hearing aids without training. Auditory processing changes were
      assessed through the use of dichotic listening tasks. RESULTS: During hearing aid
      use, dichotic listening scores-tested without the hearing aids-improved in both
      groups, mainly in the non-dominant ears. The overall dichotic performance was
      significantly higher in the study group, and the main effect of auditory training
      was manifested in the scores of the dominant ear. CONCLUSIONS: Hearing aid use
      may improve auditory processing performance as tested in unaided conditions.
      Listening training has an additional beneficial effect on the dominant ear-that
      is, the ear with the lesser potential for improvement. Listening training in
      elderly adults presumably enhanced the acclimatization process by better
      recruiting the potential for auditory plasticity and improving attention
      recruitment.

PMID- 24096866
TI  - X-linked deafness-2 (DFNX2) phenotype associated with a paracentric inversion
      upstream of POU3F4.
AB  - PURPOSE: The authors report on a 7-year-old male, designated FR, who has severe
      sensorineural hearing loss. Features include a round face, hypertelorism,
      epicanthal folds, and flat nasal root. Although there were early developmental
      concerns regarding FR, all but his speech delay resolved when he was placed in an
      educational program that accommodated his hearing loss. Genetic studies were
      performed to investigate genetic causes for his hearing loss. METHOD: History,
      physical examination, audiologic assessment, and imaging were performed according
      to usual practice. FMR1,GJB2,GJB6, and POU3F4 genes were sequenced. Chromosomal
      studies consisted of karyotyping and breakpoint analysis by fluorescence in situ
      hybridization (FISH). RESULTS: Results from FMR1,GJB2,GJB6, and POU3F4 sequencing
      and echocardiography, electrocardiogram, and abdominal ultrasound were normal. A
      computed tomography (CT) scan revealed a large fundus of the internal auditory
      canals and absence of the bony partition between the fundus and the adjacent
      cochlear turns, with a widened modiolus bilaterally. FR's CT findings were
      consistent with those described in persons with X-linked deafness-2 (DFNX2)
      hereditary deafness. FR's karyotype was 46,inv(X)(q13q24),Y.ish inv(X)(XIST+)mat.
      FISH refined the breakpoints to inv(X)(q21.1q22.3). The Xq21.1 breakpoint was
      narrowed to a 25-kb region 450 kb centromeric to the DFNX2 gene, POU3F4. There
      are rare case reports of DFNX2 patients with chromosomal rearrangements
      positioned centromeric to POU3F4 and no mutations within the gene. CONCLUSION:
      Authors hypothesized that FR's hearing loss was caused by dysregulation of POU3F4
      due to separation from regulatory elements affected by the inversion.

PMID- 24096867
TI  - Low-mass-ion discriminant equation: a new concept for colorectal cancer
      screening.
AB  - Blood metabolites can be detected as low-mass ions (LMIs) by mass spectrometry
      (MS). These LMIs may reflect the pathological changes in metabolism that occur as
      part of a disease state, such as cancer. We constructed a LMI discriminant
      equation (LOME) to investigate whether systematic LMI profiling might be applied
      to cancer screening. LMI information including m/z and mass peak intensity was
      obtained by five independent MALDI-MS analyses, using 1,127 sera collected from
      healthy individuals and cancer patients with colorectal cancer (CRC), breast
      cancer (BRC), gastric cancer (GC) and other types of cancer. Using a two-stage
      principal component analysis to determine weighting factors for individual LMIs
      and a two-stage LMI selection procedure, we selected a total of 104 and 23 major
      LMIs by the LOME algorithms for separating CRC from control and rest of cancer
      samples, respectively. CRC LOME demonstrated excellent discriminating power in a
      validation set (sensitivity/specificity: 93.21%/96.47%). Furthermore, in a fecal
      occult blood test (FOBT) of available validation samples, the discriminating
      power of CRC LOME was much stronger (sensitivity/specificity: 94.79%/97.96%) than
      that of the FOBT (sensitivity/specificity: 50.00%/100.0%), which is the standard
      CRC screening tool. The robust discriminating power of the LOME scheme was
      reconfirmed in screens for BRC (sensitivity/specificity: 92.45%/96.57%) and GC
      (sensitivity/specificity: 93.18%/98.85%). Our study demonstrates that LOMEs might
      be powerful noninvasive diagnostic tools with high sensitivity/specificity in
      cancer screening. The use of LOMEs could potentially enable screening for
      multiple diseases (including different types of cancer) from a single sampling of
      LMI information. 

PMID- 24096868
TI  - Low expression of sodium iodide symporter expression in aggressive variants of
      papillary thyroid carcinoma.
AB  - BACKGROUND: A decreased radioiodine uptake is associated with high recurrence
      rate and reduced survival in papillary thyroid carcinoma (PTC). Sodium iodide
      symporter (NIS) expression status in aggressive PTC variants is unknown. METHODS:
      NIS expression in conventional PTC and aggressive PTC variants such as tall cell
      variant (TCV) and diffuse sclerosing variant (DSPTC) was investigated using
      immunohistochemical detection. RESULTS: Patients having TCV and DSPTC were
      significantly more likely to have extrathyroidal extension and lymph nodes
      metastases (P < 0.05). Positive NIS staining was identified in 228 of 312 (73.1
      %) patients with conventional PTC, 9 of 28 (32.1 %) patients with TCV and 12 of
      30 (40.0 %) patients with DSPTC. NIS expression distinguished conventional PTC
      from TCV and DSPTC significantly (P < 0.01). CONCLUSION: Due to their low NIS
      expression, TCV and DSPTC need higher cumulative doses of radioactive iodine
      therapy to improve their prognosis.

PMID- 24096869
TI  - Hsp90 chaperones PPARgamma and regulates differentiation and survival of 3T3-L1
      adipocytes.
AB  - Adipose tissue dysregulation has a major role in various human diseases. The
      peroxisome proliferator-activated receptor-gamma (PPARgamma) is a key regulator
      of adipocyte differentiation and function, as well as a target of insulin
      sensitizing drugs. The Hsp90 chaperone stabilizes a diverse set of signaling
      'client' proteins, thereby regulates various biological processes. Here we report
      a novel role for Hsp90 in controlling PPARgamma stability and cellular
      differentiation. Specifically, we show that the Hsp90 inhibitors geldanamycin and
      novobiocin efficiently impede the differentiation of murine 3T3-L1 preadipocytes.
      Geldanamycin at higher concentrations also inhibits the survival of both
      developing and mature adipocytes, respectively. Further, Hsp90 inhibition
      disrupts an Hsp90-PPARgamma complex, leads to the destabilization and proteasomal
      degradation of PPARgamma, and inhibits the expression of PPARgamma target genes,
      identifying PPARgamma as an Hsp90 client. A similar destabilization of PPARgamma
      and a halt of adipogenesis also occur in response to protein denaturing stresses
      caused by a single transient heat-shock or proteasome inhibition. Recovery from
      stress restores PPARgamma stability and adipocyte differentiation. Thus, our
      findings reveal Hsp90 as a critical stress-responsive regulator of adipocyte
      biology and offer a potential therapeutic target in obesity and the metabolic
      syndrome. 

PMID- 24096870
TI  - Metabolic regulation of cancer cell side population by glucose through activation
      of the Akt pathway.
AB  - Side population (SP) cells within tumors are a small fraction of cancer cells
      with stem-like properties that can be identified by flow cytometry analysis based
      on their high ability to export certain compounds such as Hoechst 33342 and
      chemotherapeutic agents. The existence of stem-like SP cells in tumors is
      considered as a key factor contributing to drug resistance, and presents a major
      challenge in cancer treatment. Although it has been recognized for some time that
      tumor tissue niches may significantly affect cancer stem cells (CSCs), the role
      of key nutrients such as glucose in the microenvironment in affecting stem-like
      cancer cells and their metabolism largely remains elusive. Here we report that SP
      cells isolated from human cancer cells exhibit higher glycolytic activity
      compared to non-SP cells. Glucose in the culture environment exerts a profound
      effect on SP cells as evidenced by its ability to induce a significant increase
      in the percentage of SP cells in the overall cancer cell population, and glucose
      starvation causes a rapid depletion of SP cells. Mechanistically, glucose
      upregulates the SP fraction through ATP-mediated suppression of AMPK and
      activation of the Akt pathway, leading to elevated expression of the ATP
      dependent efflux pump ABCG2. Importantly, inhibition of glycolysis by 3-BrOP
      significantly reduces SP cells in vitro and impairs their ability to form tumors
      in vivo. Our data suggest that glucose is an essential regulator of SP cells
      mediated by the Akt pathway, and targeting glycolysis may eliminate the drug
      resistant SP cells with potentially significant benefits in cancer treatment. 

PMID- 24096872
TI  - Proline oxidase-adipose triglyceride lipase pathway restrains adipose cell death
      and tissue inflammation.
AB  - The nutrient-sensing lipolytic enzyme adipose triglyceride lipase (ATGL) has a
      key role in adipose tissue function, and alterations in its activity have been
      implicated in many age-related metabolic disorders. In adipose tissue reduced
      blood vessel density is related to hypoxia state, cell death and inflammation.
      Here we demonstrate that adipocytes of poorly vascularized enlarged visceral
      adipose tissue (i.e. adipose tissue of old mice) suffer from limited nutrient
      delivery. In particular, nutrient starvation elicits increased activity of
      mitochondrial proline oxidase/dehydrogenase (POX/PRODH) that is causal in
      triggering a ROS-dependent induction of ATGL. We demonstrate that ATGL promotes
      the expression of genes related to mitochondrial oxidative metabolism (peroxisome
      proliferator-activated receptor-alpha, peroxisome proliferator-activated receptor
      gamma coactivator-1alpha), thus setting a metabolic switch towards fat
      utilization that supplies energy to starved adipocytes and prevents cell death,
      as well as adipose tissue inflammation. Taken together, these results identify
      ATGL as a stress resistance mediator in adipocytes, restraining visceral adipose
      tissue dysfunction typical of age-related metabolic disorders. 

PMID- 24096871
TI  - Cell death and diseases related to oxidative stress: 4-hydroxynonenal (HNE) in
      the balance.
AB  - During the last three decades, 4-hydroxy-2-nonenal (HNE), a major alpha,beta
      unsaturated aldehyde product of n-6 fatty acid oxidation, has been shown to be
      involved in a great number of pathologies such as metabolic diseases,
      neurodegenerative diseases and cancers. These multiple pathologies can be
      explained by the fact that HNE is a potent modulator of numerous cell processes
      such as oxidative stress signaling, cell proliferation, transformation or cell
      death. The main objective of this review is to focus on the different aspects of
      HNE-induced cell death, with a particular emphasis on apoptosis. HNE is a special
      apoptotic inducer because of its abilities to form protein adducts and to
      propagate oxidative stress. It can stimulate intrinsic and extrinsic apoptotic
      pathways and interact with typical actors such as tumor protein 53, JNK, Fas or
      mitochondrial regulators. At the same time, due to its oxidant status, it can
      also induce some cellular defense mechanisms against oxidative stress, thus being
      involved in its own detoxification. These processes in turn limit the apoptotic
      potential of HNE. These dualities can imbalance cell fate, either toward cell
      death or toward survival, depending on the cell type, the metabolic state and the
      ability to detoxify. 

PMID- 24096874
TI  - Skepticism, empathy, and animal suffering.
AB  - The suffering of nonhuman animals has become a noted factor in deciding public
      policy and legislative change. Yet, despite this growing concern, skepticism
      toward such suffering is still surprisingly common. This paper analyzes the
      merits of the skeptical approach, both in its moderate and extreme forms. In the
      first part it is claimed that the type of criterion for verification concerning
      the mental states of other animals posed by skepticism is overly (and, in the
      case of extreme skepticism, illogically) demanding. Resting on Wittgenstein and
      Husserl, it is argued that skepticism relies on a misguided epistemology and,
      thus, that key questions posed by it face the risk of absurdity. In the second
      part of the paper it is suggested that, instead of skepticism, empathy together
      with intersubjectivity be adopted. Edith Stein's take on empathy, along with
      contemporary findings, are explored, and the claim is made that it is only via
      these two methods of understanding that the suffering of nonhuman animals can be
      perceived. 

PMID- 24096873
TI  - Connexin36 contributes to INS-1E cells survival through modulation of cytokine
      induced oxidative stress, ER stress and AMPK activity.
AB  - Cell-to-cell communication mediated by gap junctions made of Connexin36 (Cx36)
      contributes to pancreatic beta-cell function. We have recently demonstrated that
      Cx36 also supports beta-cell survival by a still unclear mechanism. Using
      specific Cx36 siRNAs or adenoviral vectors, we now show that Cx36 downregulation
      promotes apoptosis in INS-1E cells exposed to the pro-inflammatory cytokines (IL
      1beta, TNF-alpha and IFN-gamma) involved at the onset of type 1 diabetes, whereas
      Cx36 overexpression protects against this effect. Cx36 overexpression also
      protects INS-1E cells against endoplasmic reticulum (ER) stress-mediated
      apoptosis, and alleviates the cytokine-induced production of reactive oxygen
      species, the depletion of the ER Ca(2+) stores, the CHOP overexpression and the
      degradation of the anti-apoptotic protein Bcl-2 and Mcl-1. We further show that
      cytokines activate the AMP-dependent protein kinase (AMPK) in a NO-dependent and
      ER-stress-dependent manner and that AMPK inhibits Cx36 expression. Altogether,
      the data suggest that Cx36 is involved in Ca(2+) homeostasis within the ER and
      that Cx36 expression is downregulated following ER stress and subsequent AMPK
      activation. As a result, cytokine-induced Cx36 downregulation elicits a positive
      feedback loop that amplifies ER stress and AMPK activation, leading to further
      Cx36 downregulation. The data reveal that Cx36 plays a central role in the
      oxidative stress and ER stress induced by cytokines and the subsequent regulation
      of AMPK activity, which in turn controls Cx36 expression and mitochondria
      dependent apoptosis of insulin-producing cells. 

PMID- 24096875
TI  - p53's choice of myocardial death or survival: Oxygen protects infarct myocardium
      by recruiting p53 on NOS3 promoter through regulation of p53-Lys(118)
      acetylation.
AB  - Myocardial infarction, an irreversible cardiac tissue damage, involves
      progressive loss of cardiomyocytes due to p53-mediated apoptosis. Oxygenation is
      known to promote cardiac survival through activation of NOS3 gene. We
      hypothesized a dual role for p53, which, depending on oxygenation, can elicit
      apoptotic death signals or NOS3-mediated survival signals in the infarct heart.
      p53 exhibited a differential DNA-binding, namely, BAX-p53RE in the infarct heart
      or NOS3-p53RE in the oxygenated heart, which was regulated by oxygen-induced,
      post-translational modification of p53. In the infarct heart, p53 was heavily
      acetylated at Lys(118) residue, which was exclusively reversed in the oxygenated
      heart, apparently regulated by oxygen-dependent expression of TIP60. The
      inhibition of Lys(118) acetylation promoted the generation of NOS3-promoting
      prosurvival form of p53. Thus, oxygenation switches p53-DNA interaction by
      regulating p53 core-domain acetylation, promoting a prosurvival transcription
      activity of p53. Understanding this novel oxygen-p53 survival pathway will open
      new avenues in cardioprotection molecular therapy.

PMID- 24096877
TI  - Application of phase correction to improve the interpretation of crude oil
      spectra obtained using 7 T Fourier transform ion cyclotron resonance mass
      spectrometry.
AB  - In this study, a phase-correction technique was applied to the study of crude oil
      spectra obtained using a 7 T Fourier transform ion cyclotron resonance mass
      spectrometry (FT-ICR MS). 7 T FT-ICR MS had not been widely used for oil analysis
      due to the lower resolving power compared with high field FT-ICR MS. For low
      field instruments, usage of data that has not been phase-corrected results in an
      inability to resolve critical mass splits of C3 and SH4 (3.4 mDa), and (13)C and
      CH (4.5 mDa). This results in incorrect assignments of molecular formulae, and
      discontinuous double bond equivalents (DBE) and carbon number distributions of
      S1, S2, and hydrocarbon classes are obtained. Application of phase correction to
      the same data, however, improves the reliability of assignments and produces
      continuous DBE and carbon number distributions. Therefore, this study clearly
      demonstrates that phase correction improves data analysis and the reliability of
      assignments of molecular formulae in crude oil anlayses. 

PMID- 24096876
TI  - Adiponectin modulates DCA-induced inflammation via the ROS/NF-kappa B signaling
      pathway in esophageal adenocarcinoma cells.
AB  - BACKGROUND: Deoxycholic acid (DCA) promotes the development and progression of
      esophageal adenocarcinoma (EAC) by inducing inflammation. Adiponectin is reported
      to have anti-inflammatory and anti-tumor effects. PURPOSE: This study
      investigated the effects of two types of adiponectin, full-length adiponectin (f
      Ad) and globular adiponectin (g-Ad), on DCA-induced inflammation, and
      investigated the involvement of the reactive oxygen species (ROS)/NF-kappaB
      signaling pathway in inflammation in EAC. METHODS: OE19 cells were treated with
      DCA (50-300 MUM) and/or f-Ad/g-Ad (10.0 MUg/ml) or N-acetylcysteine (NAC). The
      viability of cells exposed to DCA was measured by use of the MTT assay. mRNA and
      protein levels of the inflammatory factors were examined by real-time PCR and
      ELISA. Intra-cellular ROS levels were determined by use of flow cytometry.
      Protein levels of total and p-NF-kappaB p65 were measured by western blot.
      RESULTS: DCA induced dose and time-dependent cytotoxicity. mRNA and protein
      expression of TNF-alpha, IL-8, and IL-6 in cells treated with DCA alone were up
      regulated, and intra-cellular ROS and p-NF-kappaB p65 protein levels were also
      increased. g-Ad promoted inflammatory factor production, ROS levels, and p-NF
      kappaB p65 protein expression whereas f-Ad had a suppressive effect. When
      combined with DCA, g-Ad enhanced the pro-inflammatory effect of DCA whereas f-Ad,
      similar to NAC, suppressed the effect. CONCLUSION: DCA has a pro-inflammatory
      effect in EAC. f-Ad has an anti-inflammatory effect whereas g-Ad seems to have a
      pro-inflammatory effect in an ROS/NF-kappaB p65-dependent manner. This indicates
      that f-Ad could be a potential anti-inflammatory reagent for cancer therapy.

PMID- 24096879
TI  - Exceptional fossil preservation demonstrates a new mode of axial skeleton
      elongation in early ray-finned fishes.
AB  - Elongate body plans have evolved independently multiple times in vertebrates, and
      involve either an increase in the number or in the length of the vertebrae. Here,
      we describe a new mechanism of body elongation in saurichthyids, an extinct group
      of elongate early ray-finned fishes. The rare preservation of soft tissue in a
      specimen of Saurichthys curionii from the Middle Triassic (Ladinian) of
      Switzerland provides significant new information on the relationship between the
      musculature and the skeleton. This new fossil material shows that elongation in
      these fishes results from doubling the number of neural arch-like elements per
      myomeric segment. This unique way of generating an elongate body plan
      demonstrates the evolutionary lability of the vertebral column in non-teleostean
      fishes. The shape and arrangement of preserved myosepta suggest that S. curionii
      was not a highly flexible fish, in spite of the increase in the number of neural
      arch-like elements.

PMID- 24096878
TI  - Identifying carbohydrate ligands of a norovirus P particle using a catch and
      release electrospray ionization mass spectrometry assay.
AB  - Noroviruses (NoVs), the major cause of epidemic acute gastroenteritis, recognize
      human histo-blood group antigens (HBGAs), which are present as free
      oligosaccharides in bodily fluid or glycolipids and glycoproteins on the surfaces
      of cells. The subviral P particle formed by the protruding (P) domain of the NoV
      capsid protein serves as a useful model for the study NoV-HBGA interactions.
      Here, we demonstrate the application of a catch-and-release electrospray
      ionization mass spectrometry (CaR-ESI-MS) assay for screening carbohydrate
      libraries against the P particle to rapidly identify NoV ligands and potential
      inhibitors. Carbohydrate libraries of 50 and 146 compounds, which included 18 and
      24 analogs of HBGA receptors, respectively, were screened against the P particle
      of VA387, a member of the predominant GII.4 NoVs. Deprotonated ions corresponding
      to the P particle bound to carbohydrates were isolated and subjected to collision
      induced dissociation to release the ligands in their deprotonated forms. The
      released ligands were identified by ion mobility separation followed by mass
      analysis. All 13 and 16 HBGA ligands with intrinsic affinities >500 M(-1) were
      identified in the 50 and the 146 compound libraries, respectively. Furthermore,
      screening revealed interactions with a series of oligosaccharides with structures
      found in the cell wall of mycobacteria and human milk. The affinities of these
      newly discovered ligands are comparable to those of the HBGA receptors, as
      estimated from the relative abundance of released ligand ions. 

PMID- 24096880
TI  - Abstracts of the10th Joint Meeting of the European Neuropeptide Club and Summer
      Neuropeptide Conference. May 29-June 1, 2013. Gdynia, Poland.

PMID- 24096881
TI  - Developmental changes in excitation-contraction mechanisms of the mouse
      ventricular myocardium as revealed by functional and confocal imaging analyses.
AB  - Developmental changes in excitation-contraction mechanisms were examined in the
      ventricular myocardium from fetal, neonatal, and 1-, 2-, and 4-week-old mice. In
      isolated tissue, the negative inotropic effect of nifedipine decreased, while
      that of ryanodine increased with age. Action potential duration decreased with
      age, especially during the late fetal period. In ventricular cardiomyocytes,
      fluorescence imaging revealed that the sarcoplasmic reticulum increases
      progressively during pre- and postnatal development. t-Tubules were absent in the
      fetus and neonate, were observed only in the subsarcolemmal region at 1 week
      after birth, and were present throughout the cytoplasm at 2 and 4 weeks after
      birth. The amplitude of Ca(2+) transients, as well as its ryanodine-sensitive
      component, increased with age. In the neonate and 1-week-old mice, Ca(2+) at the
      cell center showed slower rise than the subsarcolemmal region, but in 2- and 4
      week-old mice, Ca(2+) increased simultaneously across the entire width of the
      cell. These results suggest that in the mouse ventricular myocardium, the
      shortening of the action potential during the late fetal period and the
      development of t-tubule-sarcoplasmic reticulum coupling during the second
      postnatal week largely contribute to the developmental increase in the dependence
      of contraction on sarcoplasmic reticulum function. 

PMID- 24096882
TI  - Drusen measurements comparison by fundus photograph manual delineation versus
      optical coherence tomography retinal pigment epithelial segmentation automated
      analysis.
AB  - PURPOSE: To compare drusen measurements obtained from color fundus and infrared
      retromode photographs with those derived from spectral-domain optical coherence
      tomography. METHODS: Drusen lesions identified on the planar (color and infrared)
      imaging modalities were manually segmented by two independent graders using
      previously described reading center software to produce quantitative measurements
      of drusen area and number. The corresponding volume Cirrus OCT datasets were
      analyzed using commercial retinal pigment epithelium analysis algorithms to
      segment the retinal pigment epithelium band and estimated the drusen area. Drusen
      numbers were extracted from retinal pigment epithelium elevation maps. Intraclass
      correlation coefficients assessed agreement between graders; graders' average
      measurements were compared with optical coherence tomography (OCT) using paired T
      tests. RESULTS: Excellent agreement between graders was observed (r = 0.951
      0.974). No statistical difference was found in the area values obtained by color
      (0.85 +/- 0.26 mm(2), P = 0.43) or retromode (1.15 +/- 0.32 mm(2), P = 0.35)
      compared with those obtained by OCT (0.98 +/- 0.28 mm). The number of drusen
      identified by OCT (13.15 +/- 3.19) was significantly lower than that determined
      by manual segmentation of color (53.7 +/- 13.18) and retromode (100.13 +/- 16.18)
      images. CONCLUSION: Although the number of drusen individualized by commercial
      OCT algorithms is significantly lower than by planar fundus imaging modalities,
      the OCT-measured drusen area is not affected, suggesting that the algorithm
      counts confluent drusen as a single drusen.

PMID- 24096883
TI  - Hemorrhagic unilateral retinopathy.
AB  - PURPOSE: To evaluate the possible etiologies of a hemorrhagic unilateral
      retinopathy in healthy patients. METHODS: Retrospective case series and review of
      the literature. All patients underwent a detailed ophthalmologic evaluation and
      analyses of their medical histories. RESULTS: Eleven eyes of 10 patients with
      unexplained unilateral, predominantly deep, intraretinal hemorrhages were
      identified. All patients were women. Mean age of the subjects was 48.4 years
      (range, 25-83 years). The main complaint at presentation was sudden visual loss,
      with visual acuity ranging from 20/20 to hand motion. The mean follow-up was 17
      months, and the 9 eyes with follow-up showed spontaneous resolution of the
      hemorrhages and marked improvement of vision. There was no history of Valsalva
      maneuver or strenuous exercise. The patients were healthy at presentation and
      during follow-ups as long as 84 months. CONCLUSION: This series depicts the
      characteristics of a possible new entity with a review of the differential
      diagnosis. The visual outcome was excellent.

PMID- 24096884
TI  - Reply: To PMID 23518900.

PMID- 24096886
TI  - Influence of the Changjiang River flood on Synechococcus ecology in the surface
      waters of the East China Sea.
AB  - Synechococcus spp. have been suggested as the primary component of
      picophytoplankton in the East China Sea (ECS). However, the influences of sudden
      environmental changes on Synechococcus assemblage composition have not yet been
      investigated. In the summer of 2010, a disastrous flood occurred in the
      Changjiang River basin. To improve our understanding of how this flood affected
      the Synechococcus ecology on the ECS surface, their assemblages and distributions
      have been described using two-laser flow cytometry and phylogenetic analysis of
      the phycocyanin operon. During the nonflooding summer of 2009, phycoerythrin-rich
      (PE-rich) Synechococcus thrived near the outer boundary of the Changjiang River
      diluted water (CDW) coverage, while phycocyanin-rich (PC-rich) Synechococcus
      predominated inside the turbid CDW with a transparency of <80%. During the 2010
      summer, flooding expanded the CDW coverage area to over half of the ECS. PE-rich
      cells showed a homogeneous distribution and a decline in abundance, while the
      spatial pattern of the PC-rich Synechococcus resembled the pattern from 2009.
      Based on the phycocyanin operon phylogeny, the Synechococcus in the ECS were
      categorized into five groups, ECS-1 to ECS-4 and ECS-PE, comprising a total of 19
      operational taxonomic units. In the summer of 2009, ECS-2 dominated in the coast,
      and the ECS-3 and ECS-PE clades prevailed in the offshore waters. However, during
      the summer of 2010, ECS-4 and ECS-PE became the dominant strains. The injection
      of abundant anthropogenic pollutants and the enhancement of transparency within
      the CDW expansion area appear to be the factors needed to transiently alter the
      ecology of Synechococcus after flooding.

PMID- 24096887
TI  - Modifying the size and uniformity of upconversion Yb/Er:NaGdF4 nanocrystals
      through alkaline-earth doping.
AB  - NaGdF4 is regarded as an ideal upconversion (UC) host material for lanthanide
      (Ln(3+)) activators because of its unique crystal structure, high Ln(3+)
      solubility, low phonon energy and high photochemical stability, and Ln(3+)-doped
      NaGdF4 UC nanocrystals (NCs) have been widely investigated as bio-imaging and
      magnetic resonance imaging agents recently. To realize their practical
      applications, controlling the size and uniformity of the monodisperse Ln(3+)
      doped NaGdF4 UC NCs is highly desired. Unlike the routine routes by finely
      adjusting the multiple experimental parameters, herein we provide a facile and
      straightforward strategy to modify the size and uniformity of NaGdF4 NCs via
      alkaline-earth doping for the first time. With the increase of alkaline-earth
      doping content, the size of NaGdF4 NCs increases gradually, while the size
      uniformity is still retained. We attribute this "focusing" of size distribution
      to the diffusion controlled growth of NaGdF4 NCs induced by alkaline-earth
      doping. Importantly, adopting the Ca(2+)-doped Yb/Er:NaGdF4 NCs as cores, the
      complete Ca/Yb/Er:NaGdF4@NaYF4 core-shell particles with excellent size
      uniformity can be easily achieved. However, when taking the Yb/Er:NaGdF4 NCs
      without Ca(2+) doping as cores, they could not be perfectly covered by NaYF4
      shells, and the obtained products are non-uniform in size. As a result, the UC
      emission intensity of the complete core-shell NCs increases by about 30 times in
      comparison with that of the cores, owing to the effective surface passivation of
      the Ca(2+)-doped cores and therefore protection of Er(3+) in the cores from the
      non-radiative decay caused by surface defects, whereas the UC intensity of the
      incomplete core-shell NCs is enhanced by only 3 times. 

PMID- 24096888
TI  - The alligator gut microbiome and implications for archosaur symbioses.
AB  - Among vertebrate gastrointestinal microbiome studies, complete representation of
      taxa is limited, particularly among reptiles. Here, we provide evidence for
      previously unrecognized host-microbiome associations along the gastrointestinal
      tract from the American alligator, a crown archosaur with shared ancestry to
      extinct taxa, including dinosaurs. Microbiome compositional variations reveal
      that the digestive system consists of multiple, longitudinally heterogeneous
      microbiomes that strongly correlate to specific gastrointestinal tract organs,
      regardless of rearing histories or feeding status. A core alligator gut
      microbiome comprised of Fusobacteria, but depleted in Bacteroidetes and
      Proteobacteria common to mammalians, is compositionally unique from other
      vertebrate gut microbiomes, including other reptiles, fish, and herbivorous and
      carnivorous mammals. As such, modern alligator gut microbiomes advance our
      understanding of archosaur gut microbiome evolution, particularly if conserved
      host ecology has retained archosaur-specific symbioses over geologic time. 

PMID- 24096885
TI  - Pseudomonas aeruginosa biofilms in disease.
AB  - Pseudomonas aeruginosa is a ubiquitous organism that is the focus of intense
      research because of its prominent role in disease. Due to its relatively large
      genome and flexible metabolic capabilities, this organism exploits numerous
      environmental niches. It is an opportunistic pathogen that sets upon the human
      host when the normal immune defenses are disabled. Its deadliness is most
      apparent in cystic fibrosis patients, but it also is a major problem in burn
      wounds, chronic wounds, chronic obstructive pulmonary disorder, surface growth on
      implanted biomaterials, and within hospital surface and water supplies, where it
      poses a host of threats to vulnerable patients (Peleg and Hooper, N Engl J Med
      362:1804-1813, 2010; Breathnach et al., J Hosp Infect 82:19-24, 2012). Once
      established in the patient, P. aeruginosa can be especially difficult to treat.
      The genome encodes a host of resistance genes, including multidrug efflux pumps
      (Poole, J Mol Microbiol Biotechnol 3:255-264, 2001) and enzymes conferring
      resistance to beta-lactam and aminoglycoside antibotics (Vahdani et al., Annal
      Burns Fire Disast 25:78-81, 2012), making therapy against this gram-negative
      pathogen particularly challenging due to the lack of novel antimicrobial
      therapeutics (Lewis, Nature 485: 439-440, 2012). This challenge is compounded by
      the ability of P. aeruginosa to grow in a biofilm, which may enhance its ability
      to cause infections by protecting bacteria from host defenses and chemotherapy.
      Here, we review recent studies of P. aeruginosa biofilms with a focus on how this
      unique mode of growth contributes to its ability to cause recalcitrant
      infections. 

PMID- 24096889
TI  - Identification of a drought-induced rice gene, OsSAP, that suppresses Bax-induced
      cell death in yeast.
AB  - We identified rice genes that might be involved in drought stress tolerance by
      virtue of their anti-apoptotic activity. Potential anti-apoptosis related genes
      were identified by screening an Oryza sativa cDNA library derived from drought
      stressed tissues in a yeast functional assay. About 28 O. sativa cDNAs promoted
      yeast survival following engagement of Bax-induced apoptosis. An O. sativa cDNA
      encoding R12H780 was a highly conserved putative senescence-associated-protein
      (OsSAP). OsSAP was both highly and rapidly expressed in response to drought
      stress. Additionally, OsSAP was found to be localized to the mitochondria.
      Overall, OsSAP represents a new type of Bax suppressor related gene and endows
      multiple stress tolerance in yeast. 

PMID- 24096890
TI  - Development of SSR markers by next-generation sequencing of Korean landraces of
      chamoe (Cucumis melo var. makuwa).
AB  - The oriental melon (Cucumis melo var. makuwa), called 'chamoe' in Korean, is a
      popular fruit crop cultivated mainly in Asia and a high-market value crop in
      Korea. To provide molecular breeding resources for chamoe, we developed and
      characterized genomic SSR markers from the preliminary Illumina read assemblies
      of Gotgam chamoe (one of the major landraces; KM) and SW3 (the breeding parent).
      Mononucleotide motifs were the most abundant type of markers, followed by di-,
      tri-, tetra-, and pentanucleotide motifs. The most abundant dinucleotide was AT,
      followed by AG and AC, and AAT was the most abundant trinucleotide motif in both
      assemblies. Following our SSR-marker development strategy, we designed a total of
      370 primer sets. Of these, 236 primer sets were tested, exhibiting 93 %
      polymorphism between KM and SW3. Those polymorphic SSRs were successfully
      amplified in the netted and Kirkagac melons, which respectively exhibited 81 and
      76 % polymorphism relative to KM, and 32 and 38 % polymorphism relative to SW3.
      Seven selected SSR markers with a total of 17 alleles (2-3 alleles per locus)
      were used to distinguish between KM, SW3, and four chamoe cultivars. Our results
      represent the first attempt to provide genomic resources for Korean landraces for
      the purposes of chamoe breeding, as well as to discover a set of SSR markers
      capable of discriminating chamoe varieties from Korea and the rest of Asia, which
      possess little genetic diversity. This study establishes a highly efficient
      strategy for developing SSR markers from preliminary Illumina assemblies of AT
      rich genomes. 

PMID- 24096892
TI  - Aharonov-Bohm oscillations, quantum decoherence and amplitude modulation in
      mesoscopic InGaAs/InAlAs rings.
AB  - Low-temperature Aharonov-Bohm oscillations in the magnetoresistance of mesoscopic
      interferometric rings patterned on an InGaAs/InAlAs heterostructure are
      investigated for their dependence on excitation current and temperature. The
      rings have an average radius of 650 nm, and a lithographic arm width of 300 nm,
      yielding pronounced interference oscillations over a wide range of magnetic
      fields. Apart from a current and temperature dependence, the oscillation
      amplitude also shows a quasi-periodic modulation with applied magnetic field. The
      phase coherence length is extracted by analysis of the fundamental and higher
      Fourier components of the oscillations, and by direct analysis of the amplitude
      and its dependence on parameters. It is concluded that the Thouless energy forms
      the measure of excitation energies for quantum decoherence. The amplitude
      modulation finds an explanation in the effect of the magnetic flux threading the
      finite width of the interferometer arms.

PMID- 24096891
TI  - The anti-adipogenic effect of PGRN on porcine preadipocytes involves ERK1,2
      mediated PPARgamma phosphorylation.
AB  - Recent researches indicate that PGRN is closely related to diabetes and is
      regarded as a novel adipokine associated with obesity development, affecting
      adipocyte biology. In the present study, we investigated the effects and
      mechanisms of PGRN on porcine preadipocytes differentiation. Porcine
      preadipocytes were induced to differentiation with the addition of lentivirius
      expressed PGRN shRNA at the early or late stage of induction period, and in the
      presence or absence of recombinant PGRN protein. The effects of PGRN on
      adipogenic genes expression and ERK activation were investigated. At the early
      stage of induction, knockdown of PGRN promoted differentiation, evidenced by
      enhanced lipid accumulation, upregulation of adipocyte markers, as well as master
      adipogenic transcription factors, PPARgamma and C/EBPalpha. While, decreasing
      PGRN expression at the late stage of induction (day 3) had no effect on
      differentiation. These results suggested that PGRN functions in the early
      adipogenic events. Conversely, porcine preadipocytes differentiation was impaired
      by MDI and recombinant PGRN protein induction, the expressions of adipocyte
      markers were decreased. Further studies revealed that PGRN can specifically
      facilitate ERK1,2 activation, and this activation can be abolished by U0126.
      Moreover, PPARgamma phosphorylation at serine 112 site was increased by PGRN
      treatment, which could reduce the transcriptional activity of PPARgamma. We
      conclude that PGRN inhibits adipogenesis in porcine preadipocytes partially
      through ERK activation mediated PPARgamma phosphorylation. 

PMID- 24096893
TI  - Prevalence of human papillomavirus in anal and oral sites among patients with
      genital warts.
AB  - Genital warts are caused by human papillomavirus (HPV). HPV is a leading cause of
      anogenital malignancies and a role of HPV in the aetiology of oro-pharyngeal
      cancers has been demonstrated. The frequency of oral HPV infection in patients
      with genital warts and the association between concomitant genital, anal and oral
      infection is unclear. A total of 201 men and women with genital wart-like lesions
      were recruited. Swab samples were obtained from the genital warts and the anal
      canal and an oral rinse was collected. Anal HPV was found in 46.2% and oral HPV
      in 10.4% of the participants. Concordance between anal and genital wart HPV types
      was 78.1%, while concordance between oral and genital wart types was 60.9%. A
      lower concordance of 21.7% was observed between anal and oral HPV types.
      Significantly more women than men had multiple HPV types and anal HPV. In
      conclusion, extra genital HPV is common in patients with genital warts. A gender
      inequality seems to exist. 

PMID- 24096894
TI  - Applying ethnography to the study of context in healthcare quality and safety.
AB  - BACKGROUND: Translating and scaling healthcare quality improvement (QI) and
      patient safety interventions remains a significant challenge. Context has been
      identified as a major factor in this. QI and patient safety research have begun
      to focus on context, with ethnography seen as a promising methodology for
      understanding the professional, organisational and cultural aspects of context.
      While ethnography is used to investigate the context of a variety of QI and
      safety interventions, the challenges inherent in effectively importing a
      qualitative methodology and its social science practitioners into this work have
      been largely unexamined. METHOD AND RESULTS: We explain ethnography as a research
      practice grounded in theory and dependent on observations gathered and
      interpreted in particular ways. We then review the approach of health services
      literature to evaluating this sort of qualitative research. Although the study of
      context is an interest shared by both social scientists and healthcare QI and
      safety researchers, we identify three key points at which those 'exporting'
      ethnography as a methodology and those 'importing' it to deal with QI and safety
      challenges may diverge. We describe perspectival divergences on the methodology's
      mission, form and scale. At the level of mission we demonstrate how ethnography
      has been adapted to a 'describe and feed back' role in the service of QI. At the
      level of form, we show how the long-term embedded observation at the heart of
      ethnography can be adapted only so far to accommodate QI interests if both data
      quality and ethical standards are to be upheld. Finally, at the level of scale,
      we demonstrate one ethnographic study design that balances breadth of exposure
      with depth of experience in its observations and so generates a particular type
      of scalable findings. SUMMARY: The effective export of ethnography into QI and
      safety research requires discussion and negotiation between social scientific and
      health services research perspectives, as well as creative approaches to
      producing self-reflexive data that will allow clinicians to understand their own
      context and so improve their own processes.

PMID- 24096895
TI  - Leisure-time aerobic physical activity, muscle-strengthening activity and
      mortality risks among US adults: the NHANES linked mortality study.
AB  - BACKGROUND: Regular physical activity elicits multiple health benefits in the
      prevention and management of chronic diseases. We examined the mortality risks
      associated with levels of leisure-time aerobic physical activity and muscle
      strengthening activity based on the 2008 Physical Activity Guidelines for
      Americans among US adults. METHODS: We analysed data from the 1999 to 2004
      National Health and Nutrition Examination Survey with linked mortality data
      obtained through 2006. Cox proportional HRs with 95% CIs were estimated to assess
      risks for all-causes and cardiovascular disease (CVD) mortality associated with
      aerobic physical activity and muscle-strengthening activity. RESULTS: Of 10 535
      participants, 665 died (233 deaths from CVD) during an average of 4.8-year follow
      up. Compared with participants who were physically inactive, the adjusted HR for
      all-cause mortality was 0.64 (95% CI 0.52 to 0.79) among those who were
      physically active (engaging in >=150 min/week of the equivalent moderate
      intensity physical activity) and 0.72 (95% CI 0.54 to 0.97) among those who were
      insufficiently active (engaging in >0 to <150 min/week of the equivalent moderate
      intensity physical activity). The adjusted HR for CVD mortality was 0.57 (95% CI
      0.34 to 0.97) among participants who were insufficiently active and 0.69 (95% CI
      0.43 to 1.12) among those who were physically active. Among adults who were
      insufficiently active, the adjusted HR for all-cause mortality was 44% lower by
      engaging in muscle-strengthening activity >=2 times/week. CONCLUSIONS: Engaging
      in aerobic physical activity ranging from insufficient activity to meeting the
      2008 Guidelines reduces the risk of premature mortality among US adults. Engaging
      in muscle-strengthening activity >=2 times/week may provide additional benefits
      among insufficiently active adults.

PMID- 24096896
TI  - Injury rate and injury pattern among elite World Cup snowboarders: a 6-year
      cohort study.
AB  - BACKGROUND: There is limited knowledge on the injury rate and injury pattern in
      the different disciplines among elite snowboarders. OBJECTIVE: The aim of this
      study was to describe and compare the injury rate and injury pattern among the
      different International Ski Federation (Federation Internationale de Ski, FIS)
      World Cup (WC) snowboard disciplines. METHODS: We conducted retrospective
      interviews with FIS WC snowboard athletes at the end of each season in the period
      2007-2012, to register all acute injuries sustained during training or
      competition during the competitive season requiring attention by medical
      personnel. To calculate the exposure, we obtained information from result lists
      from the FIS competition database for all WC competitions for each of the
      interviewed athletes. RESULTS: We registered a total of 574 injuries among 1432
      athletes, accounting for an overall injury rate of 40.1 injuries/100
      athlete/season. A total of 171 injuries occurred during the FIS WC competitions,
      corresponding to 6.4 injuries/1000 runs. During competition, injury risk was
      highest in snowboard cross with 11.9/1000 runs, followed by 6.3 in halfpipe, 3.6
      in big air and 2.8 in parallel giant slalom/parallel slalom (PGS/PSL). Snowboard
      cross also had the highest risk of severe injuries (>28 days absence). No
      differences in injury risk were detected between male and female snowboarders.
      The most commonly injured body part was the knee (17.8%), followed by the
      shoulder/clavicle (13.4%) and head/face (13.2%). The risk of knee injury (the
      most common injury type) and head injury was significantly higher in snowboard
      cross and halfpipe compared to PGS/PSL. CONCLUSIONS: The risk of injuries was
      higher in snowboard cross than in halfpipe, big air and PGS/PSL. The most
      commonly injured body part was the knee. Prevention of snowboard injuries among
      elite snowboarders should focus on knee injuries, severe injuries and snowboard
      cross athletes.

PMID- 24096898
TI  - When can a professional athlete return to play following scapholunate ligament
      delayed reconstruction?
AB  - BACKGROUND: The aim of this study was to determine the outcomes in relation to
      return-to-play in professional athletes who had undergone a delayed scapholunate
      ligament reconstruction. METHODS: We searched our prospectively managed database
      and identified 15 professional athletes who had undergone the modified Brunelli
      procedure for scapholunate instability. They were contacted to complete a
      telephone interview. We established the duration between the operation and return
      to-play, the level of competition before and after the procedure and if
      applicable, reasons for reduction in the level of competition. RESULTS: Between
      2008 and 2011, 15 professional male athletes underwent the modified Brunelli
      procedure. One was lost to follow-up and 14 athletes (11 rugby, 2 boxing and 1
      golf) were contactable. The mean age of the patients was 30 years (range 18-42).
      The mean follow-up period was 25 months (range 3-43). Eleven of the 14 (79%)
      athletes returned to play within 4 months of surgery. By the final review, 9 of
      the 14 (64%) athletes had returned to play at their preinjury level of
      competition. CONCLUSIONS: A majority (approximately 80%) of professional athletes
      return to competitive playing within 4 months of undergoing a scapholunate
      ligament reconstruction. Approximately two-thirds return to play at their
      preinjury level of competition.

PMID- 24096899
TI  - Concussion and chronic traumatic encephalopathy: International Rugby Board's
      response.

PMID- 24096897
TI  - Sports-related extensor carpi ulnaris pathology: a review of functional anatomy,
      sports injury and management.
AB  - The extensor carpi ulnaris (ECU) muscle plays a key role not only in the active
      movements of wrist extension and ulnar deviation but also in providing stability
      to the ulnar side of the wrist. Its position relative to the other structures in
      the wrist changes with forearm pronation and supination. As such, it must be
      mobile yet stable. The ECU tendon relies on specific stabilising structures to
      hold it in the correct positions to perform its different functions. These
      structures can be injured in a variety of different athletic activities such as
      tennis, golf and rugby league, yet their injury and disruption is predictable
      when the mechanics of the ECU and the techniques of the sport are understood. The
      ECU tendon is also vulnerable to tendon pathologies other than instability. It
      lies subcutaneously and is easily palpated and visualised with diagnostic
      ultrasound, allowing early diagnosis and management of its specific conditions.
      Treatment includes rest, splintage and surgery with each modality having specific
      indications and recognised outcomes. This review described the functional anatomy
      in relevant sporting situations and explained how problems occur as well as when
      and how to intervene. 

PMID- 24096900
TI  - Association between renal vasculature changes and generalized atherosclerosis: an
      autopsy survey.
AB  - AIM: To examine the association between renal vasculature changes and generalized
      atherosclerosis using autopsy cases. METHODS: We histologically examined 107
      autopsy patients(mean age, 68.4 years; 64% men; 81% non-CVD) to investigate the
      association between renal vasculature changes and generalized atherosclerosis. We
      measured the intima/media(I/M) ratio for the renal, intrarenal and systemic
      arteries(coronary, cerebral, common carotid and common iliac), calculated the
      rates of arteriolar hyalinization and global glomerulosclerosis and evaluated the
      frequency of advanced lesions(AHA classification >=IV) in the systemic arteries.
      RESULTS: The I/M ratios of the renal and intrarenal arteries and the rate of
      global glomerulosclerosis increased with age, while the rates of arteriolar
      hyalinization and global glomerulosclerosis were associated with diabetes and
      hypertension(all p<0.05). The I/M ratio of the coronary artery was independently
      associated with the rate of global glomerulosclerosis(p<0.05). The frequency of
      advanced atherosclerotic lesions in the coronary and cerebral arteries was also
      correlated with the I/M ratio of the renal artery and rates of arteriolar
      hyalinization and global glomerulosclerosis(all p<0.05). The frequency of
      advanced lesions in the cerebral and common carotid arteries was independently
      associated with the I/M ratio of the renal artery and the rate of renal
      arteriolar hyalinization(odds ratio(OR) with [95% confidence interval]; 5.09
      [1.15-27.9] and 4.11 [1.38-13.9], respectively). CONCLUSIONS: The results of this
      study demonstrated that pathological changes in four portions of the renal
      vasculature differ. Renal vasculature changes except the intrarenal arteries were
      significantly associated with those observed in the cerebral, common carotid and
      coronary arteries.

PMID- 24096901
TI  - Control of the conformations of ion Coulomb crystals in a Penning trap.
AB  - Laser-cooled atomic ions form ordered structures in radiofrequency ion traps and
      in Penning traps. Here we demonstrate in a Penning trap the creation and
      manipulation of a wide variety of ion Coulomb crystals formed from small numbers
      of ions. The configuration can be changed from a linear string, through
      intermediate geometries, to a planar structure. The transition from a linear
      string to a zigzag geometry is observed for the first time in a Penning trap. The
      conformations of the crystals are set by the applied trap potential and the laser
      parameters, and agree with simulations. These simulations indicate that the
      rotation frequency of a small crystal is mainly determined by the laser
      parameters, independent of the number of ions and the axial confinement strength.
      This system has potential applications for quantum simulation, quantum
      information processing and tests of fundamental physics models from quantum field
      theory to cosmology. 

PMID- 24096902
TI  - Cost-effectiveness of primary prevention of paediatric asthma: a decision
      analytic model.
AB  - BACKGROUND: Many children stand to benefit from being asthma-free for life with
      primary (i.e., prenatally started) prevention addressing one environmental
      exposure in a unifaceted (UF) approach or at least two in a multifaceted (MF)
      approach. We assessed the cost-effectiveness of primary prevention programmes for
      Dutch children in a decision-analytic framework. METHODS: A decision-analytic
      tree model analysing healthcare costs and asthma cases prevented was developed to
      compare usual care (UC) with two UF and three MF programmes on the primary
      prevention of asthma amongst children. Programmes were evaluated through
      incremental cost-effectiveness ratios and net monetary benefits. Decision and
      parameter uncertainty were subjected to value-of-information analyses. RESULTS:
      The current UC and one of three MF programmes dominated the other alternatives.
      The MF programme was more costly but also more effective than UC at an
      incremental cost-effectiveness ratio of <euro>8,209.20/additional asthma case
      prevented. The value of perfect information to reduce uncertainty was
      <euro>291.6M at its lowest. Most of the uncertainty in the cost-effectiveness
      threshold was attributable to the probability and cost estimates for low-risk
      children. CONCLUSION: This study supports the feasibility of a structured
      programme that simultaneously addresses exposure to house dust mites, pet dander,
      environmental tobacco, and breast-feeding as a cost-effective alternative to UC
      in the primary prevention of asthma amongst children.

PMID- 24096903
TI  - Buckle-driven delamination of hydrophobic micro-, nano-, and heterostructured
      membranes without a sacrificial layer.
AB  - A fabrication method, based on thin film buckling, is demonstrated to form unique
      membranes that can be used for applications in optics and biosensing. This method
      should be applicable to a variety of material systems, which, along with its
      simplicity and compatibility with different film architectures, allows for
      widespread implementation. 

PMID- 24096905
TI  - Molecular dynamics simulations of longer n-alkanes in silicalite: a comparison of
      framework and hydrocarbon models.
AB  - The diffusion of n-alkanes ranging from length n-C8 to n-C20 in the zeolite
      silicalite is studied using classical molecular dynamics simulations. Different
      simulations were performed using a united-atom hydrocarbon model with a rigid
      zeolite framework, an all-atom hydrocarbon model with a rigid zeolite framework,
      and an all-atom hydrocarbon model with a flexible zeolite framework, all at 300
      K. The latter two models have never previously been used to simulate longer
      alkanes in silicalite. Diffusion coefficients measured using a rigid zeolite
      framework exhibited a periodic dependence on chain length in the [010] direction
      in line with the previously observed phenomenon of resonant diffusion, regardless
      of the hydrocarbon model used. Explanations are considered in terms of the
      location of low energy traps within the silicalite structure, presenting a
      diffusion barrier. A monotonic dependence on diffusivity with chain length was
      observed however, on using an all-atom hydrocarbon model and a flexible
      framework, which was attributed to the occurrence of pore 'breathing' assisting
      diffusion. It was also noted that the calculated diffusion coefficients were up
      to an order of magnitude lower, and experimental diffusion coefficients are in
      much closer agreement when the latter model is used. 

PMID- 24096904
TI  - The use of feathers of birds of prey as indicators of metal pollution.
AB  - Published results concerning metal levels in feathers of birds of prey were
      listed and evaluated. Mercury concentrations have been studied most and the
      background values normally vary between 0.1 and 5 mg/kg dry weight the highest
      concentrations being in birds from aquatic food chains. Pollution causes elevated
      levels of mercury in feathers. The concentrations of cadmium, copper, lead and
      zinc show reasonable variation between species, areas and time periods. Feathers
      of birds of prey have proved to be good indicators of the status of environmental
      heavy metal pollution. Special attention should be paid to clean sampling and
      preparation of samples. Interpretation of the results requires knowledge on food
      habit, molting and migration patterns of the species. Several species
      representing different food chains should be included in comprehensive monitoring
      surveys. Chick feathers reflect most reliably local conditions.

PMID- 24096906
TI  - Involvement of Botrytis cinerea small GTPases BcRAS1 and BcRAC in
      differentiation, virulence, and the cell cycle.
AB  - Small GTPases of the Ras superfamily are highly conserved proteins that are
      involved in various cellular processes, in particular morphogenesis,
      differentiation, and polar growth. Here we report on the analysis of RAS1 and RAC
      homologues from the gray mold fungus Botrytis cinerea. We show that these small
      GTPases are individually necessary for polar growth, reproduction, and
      pathogenicity, required for cell cycle progression through mitosis (BcRAC), and
      may lie upstream of the stress-related mitogen-activated protein kinase (MAPK)
      signaling pathway. bcras1 and bcrac deletion strains had reduced growth rates,
      and their hyphae were hyperbranched and deformed. In addition, both strains were
      vegetatively sterile and nonpathogenic. A strain expressing a constitutively
      active (CA) allele of the BcRAC protein had partially similar but milder
      phenotypes. Similar to the deletion strains, the CA-BcRAC strain did not produce
      any conidia and had swollen hyphae. In contrast to the two deletion strains,
      however, the growth rate of the CA-BcRAC strain was normal, and it caused delayed
      but well-developed disease symptoms. Microscopic examination revealed an
      increased number of nuclei and disturbance of actin localization in the CA-BcRAC
      strain. Further work with cell cycle- and RAC-specific inhibitory compounds
      associated the BcRAC protein with progression of the cell cycle through mitosis,
      possibly via an effect on microtubules. Together, these results show that the
      multinucleate phenotype of the CA-BcRAC strain could result from at least two
      defects: disruption of polar growth through disturbed actin localization and
      uncontrolled nuclear division due to constitutive activity of BcRAC. 

PMID- 24096908
TI  - Pulmonary cryptococcosis presenting as wandering multiple bilateral shadows and
      hilar and mediastinal lymph node enlargement in the lungs.
AB  - We present a case of pulmonary cryptococcosis presenting as wandering multiple
      bilateral shadows and hilar and mediastinal lymph node enlargement in which the
      fluconazole treatment suppressed the symptoms. This case illustrates the complex
      nature of immunological responses in the lungs and highlights the need to
      consider the existence of cryptococcal allergies. 

PMID- 24096907
TI  - Strategies to discover the structural components of cyst and oocyst walls.
AB  - Cysts of Giardia lamblia and Entamoeba histolytica and oocysts of Toxoplasma
      gondii and Cryptosporidium parvum are the infectious and sometimes diagnostic
      forms of these parasites. To discover the structural components of cyst and
      oocyst walls, we have developed strategies based upon a few simple assumptions.
      Briefly, the most abundant wall proteins are identified by monoclonal antibodies
      or mass spectrometry. Structural components include a sugar polysaccharide
      (chitin for Entamoeba, beta-1,3-linked glucose for Toxoplasma, and beta-1,3
      linked GalNAc for Giardia) and/or acid-fast lipids (Toxoplasma and
      Cryptosporidium). Because Entamoeba cysts and Toxoplasma oocysts are difficult to
      obtain, studies of walls of nonhuman pathogens (E. invadens and Eimeria,
      respectively) accelerate discovery. Biochemical methods to dissect fungal walls
      work well for cyst and oocyst walls, although the results are often unexpected.
      For example, echinocandins, which inhibit glucan synthases and kill fungi, arrest
      the development of oocyst walls and block their release into the intestinal
      lumen. Candida walls are coated with mannans, while Entamoeba cysts are coated in
      a dextran-like glucose polymer. Models for cyst and oocyst walls derive from
      their structural components and organization within the wall. Cyst walls are
      composed of chitin fibrils and lectins that bind chitin (Entamoeba) or fibrils of
      the beta-1,3-GalNAc polymer and lectins that bind the polymer (Giardia). Oocyst
      walls of Toxoplasma have two distinct layers that resemble those of fungi (beta
      1,3-glucan in the inner layer) or mycobacteria (acid-fast lipids in the outer
      layer). Oocyst walls of Cryptosporidium have a rigid bilayer of acid-fast lipids
      and inner layer of oocyst wall proteins. 

PMID- 24096909
TI  - Initial combination of injectable and oral anti-tuberculosis agents for the
      treatment of severe disseminated tuberculosis.
AB  - There is a need for intravenous therapy for severe forms of tuberculosis in those
      who are HIV-positive, diabetic, have cystic fibrosis, extensive gastrointestinal
      involvement, haemodynamic instability with difficulty to take and absorb oral
      medications, which results in a lack of appropriate therapeutic effect during
      treatment, such as not creating the optimal blood concentration of the substance.
      We report an HIV-infected patient presenting with severe disseminated
      tuberculosis with extensive intestinal involvement which was successfully treated
      with an initial combination regimen of injectable and oral anti-tuberculosis
      agents. We discuss and emphasize the importance of an initial regimen with
      injectable and oral agents for treating severe forms of tuberculosis. 

PMID- 24096911
TI  - Molecular genetic diversity of Satureja bachtiarica.
AB  - Fifty-seven genotypes from eight population of Satureja bachtiarica was evaluated
      using fifteen ISSR and eleven RAPD markers. DNA profiling using RAPD primers
      amplified 84 loci, among which 81 were polymorphic with an average of 7.36
      polymorphic fragments per locus. Also, using RAPD markers maximum and minimum
      polymorphic bands observed for Semyrom (77.38 %) and Farsan (40.48 %)
      populations, respectively. Semyrom population recorded the highest unbiased
      expected heterozygosity (0.259) and Shannon's Indices (0.38). While, the lowest
      values of unbiased expected heterozygosity (0.172) and Shannon's Index (0.245)
      were recorded for Eghlid and Farsan populations, respectively. On the other hand,
      ISSR primers produced 136 bands, from which 134 were polymorphic with an average
      of 9.06 polymorphic fragments per primer (98.52 %). The ISSR markers evaluation
      revealed that maximum and minimum polymorphic bands observed for Semyrom (66.18
      %) and Farsan (31.62 %), respectively. Shahrekorud population recorded the
      highest unbiased expected heterozygosity (0.211) and Shannon's Indices (0.301).
      While, the lowest value of unbiased expected heterozygosity (0.175) observed for
      Farsan and Yazd populations and the lowest Shannon's Index (0.191) recorded by
      Farsan population. The overall results of the study revealed that both ISSR and
      RAPD markers were effective for evaluation of genetic variation of S.
      bachtiarica.

PMID- 24096910
TI  - Developmental mapping of small-conductance calcium-activated potassium channel
      expression in the rat nervous system.
AB  - Early electrical activity and calcium influx regulate crucial aspects of neuronal
      development. Small-conductance calcium-activated potassium (SK) channels regulate
      action potential firing and shape calcium influx through feedback regulation in
      mature neurons. These functions, observed in the adult nervous system, make them
      ideal candidates to regulate activity- and calcium-dependent processes in
      neurodevelopment. However, to date little is known about the onset of expression
      and regions expressing SK channel subunits in the embryonic and postnatal
      development of the central nervous system (CNS). To allow studies on the
      contribution of SK channels to different phases of development of single neurons
      and networks, we have performed a detailed in situ hybridization mapping study,
      providing comprehensive distribution profiles of all three SK subunits (SK1, SK2,
      and SK3) in the rat CNS during embryonic and postnatal development. SK channel
      transcripts are expressed at early stages of prenatal CNS development. The three
      SK channel subunits display different developmental expression gradients in
      distinct CNS regions, with time points of expression and up- or downregulation
      that can be associated with a range of diverse developmental events. Their early
      expression in embryonic development suggests an involvement of SK channels in the
      regulation of developmental processes. Additionally, this study shows how the
      postnatal ontogenetic patterns lead to the adult expression map for each SK
      channel subunit and how their coexpression in the same regions or neurons varies
      throughout development.

PMID- 24096912
TI  - Comparison of the development of performance skills in ultrasound-guided regional
      anesthesia simulations with different phantom models.
AB  - BACKGROUND: Ultrasound-guided regional anesthesia (UGRA) skills are traditionally
      obtained by supervised performance on patients, but practice on phantom models
      improves success. Currently available models are expensive or use perishable
      products, for example, olive-in-chicken breasts (OCB). We constructed 2
      inexpensive phantom (transparent and opaque) models with readily available
      nonperishable products and compared the process of learning UGRA skills by novice
      practitioners on these models with the OCB model. METHODS: Three experts first
      established criteria for a satisfactory completion of the simulated UGRA task in
      the 3 models. Thirty-six novice trainees (<20 previous UGRA experience) were
      randomly assigned to perform a UGRA task on 1 of 3 models-the transparent,
      opaque, and OCB models, where the hyperechoic target was identified, a needle was
      advanced to it under ultrasound guidance, fluid was injected, and images were
      saved. We recorded the errors during task completion, number of attempts and
      needle passes, and the time for target identification and needle placement until
      the predetermined benchmark of 3 consecutive successful UGRA simulations was
      accomplished. RESULTS: The number of errors, needle passes, and time for task
      completion per attempt progressively decreased in all 3 groups. However, failure
      to identify the target and to visualize the needle on the ultrasound image
      occurred more frequently with the OCB model. The time to complete simulator
      training was shortest with the transparent model, owing to shorter target
      identification times. However, trainees were less likely to agree strongly that
      this model was realistic for teaching UGRA skills. CONCLUSIONS: Training on
      inexpensive synthetic simulation models with no perishable products permits
      learning of UGRA skills by novices. The OCB model has disadvantages of containing
      potentially infective material, requires refrigeration, cannot be used after
      multiple needle punctures, and is associated with more failures during simulated
      UGRA. Direct visualization of the target in the transparent model allows the
      trainee to focus on needle insertion skills, but the opaque model may be more
      realistic for learning target identification skills required when UGRA is
      performed on real patients in the operating room.

PMID- 24096913
TI  - Adaptation of the US Army's After-Action Review for simulation debriefing in
      healthcare.
AB  - SUMMARY STATEMENT: Postsimulation debriefing is a critical component of effective
      learning in simulation-based health care education. Numerous formats in which to
      conduct the debriefing have been proposed. In this report, we describe the
      adaptation the US Army's After-Action Review (AAR) debriefing format for
      postsimulation debriefing in health care. The Army's AAR format is based on sound
      educational theory and has been used with great success in the US Army and
      civilian organizations for decades. Debriefing using the health care simulation
      AAR process requires planning, preparation, and follow-up. Conducting a
      postsimulation debriefing using the health care simulation AAR debriefing format
      includes 7 sequential steps as follows: (1) define the rules of the debriefing,
      (2) explain the learning objectives of the simulation, (3) benchmark performance,
      (4) review what was supposed to happen during the simulation, (5) identify what
      actually happened, (6) examine why events occurred the way they did, and (7)
      formalize learning by reviewing with the group what went well, what did not go
      well and what they would do differently if faced with a similar situation in real
      life. We feel that the use of the health care simulation AAR debriefing format
      provides a structured and supported method to conduct an effective postsimulation
      debriefing, with a focus on the learning objectives and reliance on preidentified
      performance standards.

PMID- 24096914
TI  - Simulation in the early management of gastroschisis.
AB  - AIM: Our aim was to design, create, and validate a simulator model and simulation
      scenario for the early management of gastroschisis. METHODS: Candidates of
      varying surgical experience had 1 attempt on an abdominal wall defect simulator
      and were scored for 4 different aspects: resuscitation of the neonate,
      application of a silo by both a global rating scale and a procedure-specific
      checklist, and nontechnical skills (scored by Non-Technical Skills scale).
      Surgical trainees subsequently received a focused teaching module on the
      resuscitative management and the surgical decision-making process, including
      bowel protection methods. Trainees then had a second attempt, which was
      objectively analyzed for improvement. RESULTS: Candidates attempted the
      simulation and were assessed, looking for construct validity. There was a
      statistically significant difference between candidate experience levels for all
      aspects of the simulation (resuscitation, global rating scale, procedure-specific
      checklist, and nontechnical skills) calculated using analysis of variance.
      Feedback forms gave us face validity, with a mean adjusted score of 8.3/10 for
      realism. After teaching the module, there was a statistically significant
      improvement (P < 0.05) of 20% for technical skills and 10% for nontechnical
      skills, which is comparable with similar controlled studies. CONCLUSIONS: We
      showed that creating and running a simulation scenario for the early management
      of gastroschisis is a feasible and useful tool for training and assessment. The
      simulation may also be able to discriminate between experience levels and could
      be used as a teaching aid to improve a surgeon's technical and nontechnical
      skills.

PMID- 24096915
TI  - Adolescent health care and the trainee: roles of self-efficacy, standardized
      patients, and an adolescent medicine rotation.
AB  - PURPOSE: Pediatric residents often cite a lack of confidence with adolescents
      owing to minimal exposure during training. Self-efficacy has been evaluated in a
      general context but not in relation to perception of knowledge and communication
      skill. Study objectives were to evaluate resident self-efficacy during a month
      long adolescent rotation and to assess knowledge and communication skills in
      their relationship to self-efficacy. METHODS: Data were collected as part of the
      adolescent medicine rotation for pediatric residents at a local children's
      hospital. Residents completed 2 standardized patient cases at the beginning of
      the rotation and a self-efficacy instrument before/after the cases and at the end
      of the rotation. The study assessed trends in self-efficacy using repeated
      measures analysis of variance and chi tests to examine relationships between self
      efficacy and knowledge as well as communication in preventative and sexually
      transmitted infection adolescent health. RESULTS: Resident (n = 44) self-efficacy
      levels significantly changed over all time points and were significantly related
      to knowledge and communication levels. Although self-efficacy levels decreased
      immediately after the standardized patient cases, all self-efficacy items were
      significantly higher at the end of the rotation. Residents confident or very
      confident in general health topics were deficient in asking basic history items
      and residents confident or very confident in high-risk topics often did not
      actually assess these areas with patients. CONCLUSIONS: Residents' personal
      assessments on paper may differ from actual clinical interactions. Standardized
      patient cases expose resident strengths and weaknesses with adolescents, and a
      month-long adolescent rotation allows for repetitive experiences with special
      adolescent health care topics with associated increase in self-efficacy,
      knowledge application, and communication skill.

PMID- 24096916
TI  - Training of different endoscopic skills on ex-vivo animal model.
AB  - INTRODUCTION: Virtual reality simulator and ex vivo animal models are used for
      training of both basic and advanced endoscopic techniques. The aim of this study
      was to assess whether hands-on training on ex vivo animal model improves
      endoscopic skills. Four different endoscopic techniques were practiced:
      endoscopic resection, endoscopic stenting, application of the over-the-scope
      (OVESCO) clip, and endoscopic submucosal dissection (ESD). METHODS: Except for 2
      participants, all trainees participated in a 1-day course. Two remaining
      participants took part in 7 ESD courses. All training courses consisted of
      theoretical introduction and a 6-hour training on Erlangen Active Training
      Simulator. The endoscopic skills were assessed before and after the training
      session by 2 independent assessors. Each assessor evaluated the skills by using a
      score on a scale of 1 to 5, where 1 stands for excellent and 5 for insufficient.
      Each assessor also assessed whether the procedure was successfully completed. The
      main outcome measurement was the percentage of participants who successfully
      completed the procedure during the test. RESULTS: For endoscopic resection,
      endoscopists (n = 15) improved their skills (median [10th and 90th percentiles]
      score before training, 3.5 [2.7-4.2]; after training 1.5 [1-2.3], P < 0.001).
      Seven procedures were assessed as successful before the course (47%); after the
      training, 13 procedures were assessed as successful (87%) (P = 0.02). For
      stenting, participants (n = 15) significantly improved their abilities to place
      both self-expandible metallic and plastic stents. For OVESCO clip (n = 10),
      participants (n = 10) improved their skills to prepare and apply the clip (given
      the score of 4.5 [3.9-5] before and 2.0 [1.2-2.8] after, P < 0.01). Before the
      training, only 1 clip application had been successful (10%), whereas the number
      rose to 9 after the course (90%). For endoscopic submucosal dissection (n = 10),
      eight participants of the 1-day course did not improve their competences (with
      scores of 4.2 [3.8-5] before and 4.0 [3.1-4.8] after, nonsignificant). Two
      participants who had undertaken 7 ESD courses improved their skills (with scores
      of 4 before and 1.6 after); given the small number of participants, this finding
      is statistically insignificant. LIMITATION: The effect of training on clinical
      outcome was not investigated. There was a lack of pretraining versus posttraining
      tests blinding. CONCLUSIONS: A 1-day training course on ex vivo animal model
      improves general endoscopic competence on simulator in endoscopic resection,
      insertion of stents, and application of OVESCO clips. In contrast, 1-day course
      does not improve skills for ESD that requires a higher number of training
      courses.

PMID- 24096917
TI  - In situ simulation to assess workplace attitudes and effectiveness in a new
      facility.
AB  - INTRODUCTION: In situ simulation within new facilities holds the promise of
      identifying latent safety threats. The aim of this study was to identify if in
      situ simulation can also impact important employee perceptions and attitudes.
      METHODS: In the current study, health care professionals of an adult, urban,
      community teaching hospital level 1 trauma center participated in simulated
      scenarios in a new emergency department. Before and after the simulated
      scenarios, participants provided responses to the variables regarding their
      ability to work in the new facility and other work-related variables. RESULTS:
      Significant increases in communication (P = 0.05), facility clinical readiness (P
      < 0.05), self-efficacy (P < 0.01), trauma readiness (P < 0.01), and work space
      satisfaction (P < 0.05) were found from presimulation to postsimulation. The
      results also demonstrated a significant decrease from presimulation to
      postsimulation with performance beliefs (P < 0.001). Finally, cardiac readiness
      did not reveal a significant change from presimulation to postsimulation.
      DISCUSSION: In situ simulation exercises before practicing clinically in a new
      facility can both increase familiarity with new clinical environments and impact
      important organizational outcomes. Thus, simulation in a new work space can
      influence factors important to employees, organizations, and patients.

PMID- 24096918
TI  - Integrating actors into a simulation program: a primer.
AB  - We describe our more than 10 years' experience working with actors and provide a
      "how-to" guide to recruiting, auditioning, hiring, training, and mentoring actors
      for work as simulated patients in simulation programs. We contend that trained
      actors add great realism, richness, and depth to simulation-based training
      programs. The actors experience satisfaction from their contributions, and their
      skill and improvisational talent allow programs to offer ethical and relational
      training, customized to a wide range of practitioners and adapted across a
      variety of health care conversations. Such learning opportunities can directly
      address Accreditation Council for Graduate Medical Education core competencies in
      preparing capable, confident, and empathic health care practitioners.

PMID- 24096919
TI  - A randomized controlled trial on 2 simulation-based training methods in
      radiology: effects on radiologic technology student skill in assessing image
      quality.
AB  - INTRODUCTION: A simulator for virtual radiographic examinations was developed. In
      the virtual environment, the user can perform and analyze radiographic
      examinations of patient models without the use of ionizing radiation. We
      investigated if this simulation technique could improve education of radiology
      technology students. We compared student performance in the assessment of
      radiographic image quality after training with a conventional manikin or with the
      virtual radiography simulator. METHODS: A randomized controlled experimental
      study involving 31 first-year radiology technology students was performed. It was
      organized in 4 phases as follows: (I) randomization to control or experimental
      group based on the results of an anatomy examination; (II) proficiency testing
      before training; (III) intervention (control group, exposure and analysis of
      radiographic images of the cervical spine of a manikin; experimental group,
      exposure and analysis of the cervical spine images in the virtual radiography
      simulator); and (IV) proficiency testing after training. RESULTS: The
      experimental group showed significantly higher scores after training compared
      with those before training (P < 0.01). A linear mixed-effect analysis revealed a
      significant difference between the control and experimental groups regarding
      proficiency change (P = 0.01). CONCLUSIONS: Virtual radiographic simulation is an
      effective tool for learning image quality assessment. Simulation can therefore be
      a valuable adjunct to traditional educational methods and reduce exposure to x
      rays and tutoring time.

PMID- 24096920
TI  - Does the sequence of instruction matter during simulation?
AB  - INTRODUCTION: Instructional strategies must be balanced when subjecting students
      to full-immersion simulation so as not to discourage learning and increase
      cognitive overload. The purpose of this study was to determine if participating
      in a simulation exercise before lecture yielded better performance outcomes among
      novice learners. METHODS: Twenty-nine participants were divided into 2 groups as
      follows: group 1 participated in simulation exercises followed by a didactic
      lecture and group 2 participated in the same learning activities presented in the
      opposite order. Participants were administered a multiple-choice cognitive
      assessment upon completion of a workshop. RESULTS: Learners who participated in
      the simulated exercises followed by the didactic lecture performed better on
      postassessments as compared with those who participated in the simulation after
      the lecture. A repeated-measures or nested analysis of variance generated
      statistically significant results in terms of model fit F (alpha=0.05;
      4.54)=176.07 with a P<0.0001. Despite their higher levels of increased
      performance, 76% of those who participated in simulation activities first
      indicated that they would have preferred to participate in a lecture first.
      CONCLUSIONS: The findings of this study suggest that differences occur among
      learners when the sequencing of instructional components is altered. Learners who
      participated in simulation before lecture demonstrated increased knowledge
      compared with learners who participated in simulation after a lecture.

PMID- 24096921
TI  - Role of simulation in arthroscopy training.
AB  - Arthroscopy uses a completely different skill set compared with open orthopedic
      surgery. Hitherto, arthroscopy had not been given enough emphasis in the core
      orthopedic curricula. Simulation has been seen as an excellent way to teach the
      skills required in arthroscopy. The simulators used for arthroscopy training can
      be broadly classified into physical simulators such as cadavers, animals, models
      and box trainers, virtual-reality simulators, and hybrid simulators that combine
      virtual-reality simulation with physical components that allow real tactile
      feedback. The advantages and disadvantages of each of these types have been
      described in this article. The factors that determine skill acquisition using
      these simulators have been highlighted. In conclusion, simulation seems to be a
      valuable tool for arthroscopy training, although further studies are needed to
      state whether this translates into better operative skill on real patients.

PMID- 24096922
TI  - Evaluation of a simulation-based pediatric clinical skills curriculum for medical
      students.
AB  - INTRODUCTION: Simulation-based education is expensive and requires greater
      resources than traditional methods, yet there is limited evidence to justify such
      expenditures for medical student education. METHODS: We describe the
      implementation and evaluation of a simulation-based curriculum delivered to
      medical students during a pediatric clerkship. This prospective mixed-methods
      study evaluated a 5-day long simulation-based clinical skills curriculum (PRE
      Clerkship EDucational Exercises [PRECEDE]) at the Johns Hopkins University School
      of Medicine. Two hundred medical students participated in PRECEDE during a 2-year
      period and were compared with 236 students who had not. Outcomes were assessed
      across 3 levels of Kirkpatrick's framework for evaluation. The 4-level model
      consists of reaction, learning, behavior, and results criteria. Secondary
      outcomes measured changes in assessment scores across 16 student performance
      domains during clerkship, changes in performance on the National Board of Medical
      Examiners subject examination in pediatrics, and student assessments of the
      curriculum. RESULTS: Improvements were noted across 3 levels of the Kirkpatrick's
      model. Student performance evaluations were significantly higher across all 16
      evaluation components, with effect sizes ranging from small to medium (Cohen's d,
      0.23-0.44). Students scored significantly higher on the National Board of Medical
      Examiners pediatric shelf examination (80 vs. 77, P<0.001). Ninety-seven percent
      of the medical students agreed that their skills increased and that the time lost
      to real clinical experiences was a worthwhile trade-off for this curriculum
      CONCLUSIONS: The implementation of a simulation-based curriculum within a
      pediatrics clerkship resulted in higher knowledge scores and led to improvements
      in medical student clinical performance during the clerkship.

PMID- 24096923
TI  - Teaching and the life history of cultural transmission in Fijian villages.
AB  - Much existing literature in anthropology suggests that teaching is rare in non
      Western societies, and that cultural transmission is mostly vertical (parent-to
      offspring). However, applications of evolutionary theory to humans predict both
      teaching and non-vertical transmission of culturally learned skills, behaviors,
      and knowledge should be common cross-culturally. Here, we review this body of
      theory to derive predictions about when teaching and non-vertical transmission
      should be adaptive, and thus more likely to be observed empirically. Using three
      interviews conducted with rural Fijian populations, we find that parents are more
      likely to teach than are other kin types, high-skill and highly valued domains
      are more likely to be taught, and oblique transmission is associated with high
      skill domains, which are learned later in life. Finally, we conclude that the
      apparent conflict between theory and empirical evidence is due to a mismatch of
      theoretical hypotheses and empirical claims across disciplines, and we reconcile
      theory with the existing literature in light of our results. 

PMID- 24096924
TI  - Serum cholesterol by morbidly obese patients after laparoscopic sleeve
      gastrectomy and additional physical activity.
AB  - BACKGROUND: Laparoscopic sleeve gastrectomy (LSG) has shown to be effective in
      serum triglycerides reduction and HDL cholesterol increase, but with little
      effect on total cholesterol and LDL cholesterol. Physical activity is recognized
      as an effective non-pharmacological intervention to reduce body fat mass and
      hypercholesterolemia. METHODS: A prospective observational study of all the
      patients undergoing LSG as bariatric technique between 2007 and 2012 was
      performed. All patients completed the Spanish Version of the Modifiable Physical
      Activity Questionnaire at two time points: baseline (pre-intervention) and 1 year
      after surgery, both in face-to-face interviews. Lipid profiles were monitored at
      the same time points. RESULTS: A total of 50 patients were included in the study,
      44 females (88 %) and six males (12 %) with a mean age of 42.7 +/- 10.3 years.
      Comorbidities included dyslipidemia in 50 % (40 % hypercholesterolemia and 10 %
      hypertriglyceridemia). Preoperatively, four patients (8 %) reported moderately
      active physical activity and one patient (2 %) active physical exercise. The rest
      of the patients were sedentary. One year after surgery, 30 patients (60 %)
      performed any kind of active physical activity, while the rest were sedentary.
      Lipid profile 12 months after surgery showed significantly lower total
      cholesterol levels in the active group (182.8 mg/dl vs 220 mg/dl in the sedentary
      group; p = 0.003). LDL cholesterol levels were also lower in the active group
      (103.2 vs 133 mg/dl in the sedentary group; p = 0.015). CONCLUSION: The
      performance of routine moderate physical activity in addition to LSG achieves a
      significant improvement in all parameters of the lipid profile.

PMID- 24096925
TI  - A growing problem: implications of obesity on the provision of trauma care.
AB  - The incidences of both trauma and obesity are rapidly on the rise. Whilst
      dedicated trauma centres exist, these may not be equipped to manage obese and
      super-obese patients' unique medical and surgical demands. This review assesses
      the impact of trauma on the obese patient and the specialist considerations
      required in their management throughout pre-hospital, acute and inpatient phases
      of trauma care. Specific recommendations for the necessary infrastructure and
      equipment are made to ensure optimal care of the obese trauma patient. We also
      review evidence-based best practice in the assessment, diagnosis and treatment of
      this patient group. Only by addressing the unique needs of obese trauma patients
      with specialist education, equipment and infrastructure can optimal patient
      outcomes be assured. 

PMID- 24096926
TI  - Telmisartan reduces mortality and left ventricular hypertrophy with
      sympathoinhibition in rats with hypertension and heart failure.
AB  - BACKGROUND: Angiotensin II type 1 receptor (AT1R) blockers have various benefits
      on hypertension and/or heart failure. We demonstrated that telmisartan (TLM), an
      AT1R blocker, causes sympathoinhibition by reduction of reactive oxygen species
      (ROS) in the rostral ventrolateral medulla (RVLM) of stroke-prone spontaneously
      hypertensive rats (SHRSPs). The aim of this study was to determine whether TLM
      improves survival in rats with hypertension and heart failure. METHODS:
      Angiotensin II-infused and salt-loaded SHRSPs were divided into TLM-treated,
      candesartan cilexetil (CAN)-treated, and control groups. We determined the dose
      of TLM or CAN with similar depressor effects. We examined survival, urinary
      norepinephrine excretion (uNE) as a parameter of sympathoexcitation, ROS in the
      RVLM, and left ventricular (LV) end-diastolic pressure (LVEDP). LV hypertrophy
      (LVH) was assessed by echocardiography and heart/body weight. RESULTS: Compared
      with the control group, TLM improved survival to a greater extent than CAN. At 4
      weeks after treatment, ROS in the RVLM and uNE were significantly lower in the
      TLM-treated group than in the CAN-treated group, despite the similar depressor
      effects. At 8 weeks after the treatments, LVH and LVEDP were attenuated in the
      TLM-treated group compared with the CAN-treated group. CONCLUSIONS: Our results
      suggest that TLM has the potential to reduce mortality, LVH, and LVEDP and that
      enhanced sympathoinhibition by reduction of ROS in the RVLM might be one of the
      mechanisms contributing to the beneficial actions of TLM in a model of rats with
      severe hypertension and heart failure.

PMID- 24096927
TI  - Uranium distribution in broiler organs and possibilities for protection.
AB  - The aim of the present study was to investigate the distribution of uranium
      (uranyl nitrate hexahydrate, UN) in muscle and organs (kidney, liver, and brain)
      of broilers, after a 7-day contamination with UN and administration of two
      different adsorbents (organobentonite and organozeolite). The birds were
      contaminated during 7 days with 25 mg/UN per day. Adsorbents were given via
      gastric tube, immediately after contamination with UN. In group 1 that did not
      receive any adsorbents, histopathological changes in the contaminated broilers
      were observed in small intestine, liver, and kidney in the form of necrosis of
      intestinal villi, oedema and cytoplasmic vacuolation of hepatocytes, and
      dystrophic changes in the kidney tubules epithelium. Organobentonite administered
      via gastric tube (group 2) reduced uranium distribution by 66 % in kidney, 81 %
      in liver, and 34 % in brain. In group 3, administration of organozeolite reduced
      uranium distribution by 67 % in kidney, 68 % in liver, and 49 % in brain. In
      groups 2 and 3, where the broilers received adsorbents immediately after the UN
      contamination, no histopathological lesions were observed.

PMID- 24096928
TI  - Integrated solid/nanoporous copper/oxide hybrid bulk electrodes for high
      performance lithium-ion batteries.
AB  - Nanoarchitectured electroactive materials can boost rates of Li
      insertion/extraction, showing genuine potential to increase power output of Li
      ion batteries. However, electrodes assembled with low-dimensional nanostructured
      transition metal oxides by conventional approach suffer from dramatic reductions
      in energy capacities owing to sluggish ion and electron transport kinetics. Here
      we report that flexible bulk electrodes, made of three-dimensional bicontinuous
      nanoporous Cu/MnO2 hybrid and seamlessly integrated with Cu solid current
      collector, substantially optimizes Li storage behavior of the constituent MnO2.
      As a result of the unique integration of solid/nanoporous hybrid architecture
      that simultaneously enhances the electron transport of MnO2, facilitates fast ion
      diffusion and accommodates large volume changes on Li insertion/extraction of
      MnO2, the supported MnO2 exhibits a stable capacity of as high as ~1100 mA h g(
      1) for 1000 cycles, and ultrahigh charge/discharge rates. It makes the
      environmentally friendly and low-cost electrode as a promising anode for high
      performance Li-ion battery applications. 

PMID- 24096929
TI  - Treatment options for patients with poor clopidogrel response.
AB  - A significant percentage of patients demonstrate a poor antiplatelet response to
      clopidogrel. With the emergence of testing for genetic variations in drug
      metabolizing enzyme function and testing for platelet function, it is becoming
      more common to identify patients as poor responders to clopidogrel. This leaves
      the clinician in a difficult situation when confronted with a patient deemed to
      be a poor clopidogrel responder as there is no clear therapeutic strategy for
      treating these patients. In this situation, a number of alternatives to
      conventional dosing of clopidogrel have been investigated, including increasing
      the dosage of clopidogrel, switching from clopidogrel to either prasugrel or
      ticagrelor, or adding cilostazol to clopidogrel therapy. All of these options
      have demonstrated pharmacologic benefit in terms of greater antiplatelet effects
      compared with standard clopidogrel dosing in patients with high on-treatment
      platelet reactivity or a genetic loss-of-function variant of CYP2C19, the main
      enzyme responsible for clopidogrel activation. However, the impact of each of
      these alternative therapies on clinical outcomes is poorly understood. Early
      studies have not shown a clinical benefit by increasing the clopidogrel dosage or
      switching to prasugrel although there is still much to be discovered in this
      area. Of the alternatives to standard dosing of clopidogrel, switching to either
      prasugrel or ticagrelor has the most potential benefit, but again, there is
      limited evidence to support this practice in patients who demonstrate high on
      treatment platelet reactivity while on clopidogrel although the evidence is
      somewhat more supportive in patients who have a CYP2C19 loss-of-function variant
      allele. The evidence for increasing the dosage of clopidogrel or adding
      cilostazol is the least supportive, making these alternatives difficult to
      justify. Given the limited evidence to support switching treatments, some
      providers may simply opt to continue standard dosing of clopidogrel pending the
      results of ongoing trials. Much research is needed and is currently underway in
      this area, which will be helpful in establishing future treatment protocols for
      patients with poor clopidogrel response. 

PMID- 24096930
TI  - The nucleolus fine-tunes the orchestration of an early neuroprotection response
      in neurodegeneration.

PMID- 24096931
TI  - p53 talks to PARP: the increasing complexity of p53-induced cell death.

PMID- 24096932
TI  - Seeking a MCL-1 inhibitor.

PMID- 24096933
TI  - In the race for protection, ARF comes second.

PMID- 24096934
TI  - Interaction of a synthetic antimicrobial peptide with model membrane by
      fluorescence spectroscopy.
AB  - Static and time-resolved fluorescence of tryptophan and ortho-aminobenzoic acid
      was used to investigate the interaction of the synthetic antimicrobial peptide
      L1A (IDGLKAIWKKVADLLKNT-NH2) with POPC and POPC:POPG. N-acetylated (Ac-L1A) and N
      terminus covalently bonded ortho-aminobenzoic acid (Abz-L1A-W8V) were also used.
      Static fluorescence and quenching by acrylamide showed that the peptides
      adsorption to the lipid bilayers was accompanied by spectral blue shift and by a
      decrease in fluorescence quenching, indicating that the peptides moved to a less
      polar environment probably buried in the lipidic phase of the vesicles. These
      results also suggest that the loss of the N-terminus charge allowed deeper
      fluorophore insertion in the bilayer. Despite the local character of
      spectroscopic information, conclusions can be drawn about the peptides as a
      whole. The dynamic behaviors of the peptides are such that the mean intensity
      lifetimes, the long correlation time and the residual anisotropy at long times
      increased when the peptides adsorb in lipid vesicles, being larger in anionic
      vesicles. From the steady-state increase in fluorescence intensity and
      anisotropy, we observed that the partition coefficient of peptides L1A and its
      Abz analog in both types of vesicles are higher than the acetylated analog;
      moreover, the affinity to the anionic vesicle is higher than to the zwitterionic.

PMID- 24096935
TI  - Paeoniflorin inhibits inflammatory responses in mice with allergic contact
      dermatitis by regulating the balance between inflammatory and anti-inflammatory
      cytokines.
AB  - OBJECTIVE: Paeoniflorin (Pae) was previously reported to inhibit inflammation in
      the skin of mice with allergic contact dermatitis (ACD); however, the mechanism
      remains unclear. The primary purpose of this study was to investigate the effect
      of Pae on the regulation of cytokine production in a murine model of ACD.
      METHODS: ACD was induced in the mice by repeated application of
      dinitrochlorobenzene (DNCB) to their skin. Cutaneous inflammation was evaluated
      by measuring ear swelling and by histological examination. The cytokine levels
      were measured by enzyme-linked immunosorbent assays. RESULTS: The results showed
      that topical application of DNCB caused obvious swelling and inflammatory cell
      infiltration. Treatment with Pae (70 or 140 mg/kg/d) significantly inhibited the
      cutaneous inflammation and decreased thymocyte proliferation in the mice with
      ACD. Additional data indicated that Pae increased interleukin-4 (IL-4) and IL-10
      production but reduced IL-2 and IL-17 levels in the serum as well as in thymocyte
      and splenocyte culture supernatants. As expected, IL-2 and IL-17 levels in the
      serum displayed a significant positive correlation with the severity of skin
      inflammation. In contrast, IL-4 and IL-10 levels were negatively correlated with
      the inflammation. CONCLUSIONS: The anti-inflammatory action of Pae in the murine
      model of ACD may be related to its regulation of an imbalanced cytokine
      production.

PMID- 24096936
TI  - High-density lipoprotein levels have markedly increased over the past twenty
      years in Japan.
AB  - AIM: The high-density lipoprotein cholesterol(HDL-C) level is a major negative
      risk factor for atherosclerotic diseases dependent on various lifestyle
      parameters. Changes in the lifestyle of Japanese individuals over the past
      several decades is believed to have increased their total cholesterol levels and
      the incidence of cardiovascular disease in Japan. It is therefore important to
      assess the long-term trends in the HDL-C levels with respect to public health in
      the community. METHODS: In this study, accumulated data for the serum/plasma HDL
      C levels published in cohort studies and obtained during health checkup programs
      in Japan were analyzed with respect to timedependent changes. RESULTS: The levels
      of HDL-C have continuously and significantly increased over the past 20 years by
      12-15% according to the National Health and Nutrition Study, other cohort studies
      and commercially available data. On the other hand, the non-HDL-cholesterol
      levels demonstrated no changes or only a slight decrease during the same period.
      This finding is consistent with several sets of data obtained from health checkup
      programs. The commercially measured levels of serum apoA-I, an independent
      parameter of serum HDL, also showed a similar long-term increase, supporting the
      above findings. CONCLUSION: We concluded that the serum/plasma HDL concentrations
      in Japanese individuals, selectively, have increased continuously and
      significantly over the past 20 years or more. The reasons for this phenomenon and
      the consequent public health outcomes have yet to be investigated.

PMID- 24096937
TI  - Network modularity reveals critical scales for connectivity in ecology and
      evolution.
AB  - For nearly a century, biologists have emphasized the profound importance of
      spatial scale for ecology, evolution and conservation. Nonetheless, objectively
      identifying critical scales has proven incredibly challenging. Here we extend new
      techniques from physics and social sciences that estimate modularity on networks
      to identify critical scales for movement and gene flow in animals. Using four
      species that vary widely in dispersal ability and include both mark-recapture and
      population genetic data, we identify significant modularity in three species, two
      of which cannot be explained by geographic distance alone. Importantly, the
      inclusion of modularity in connectivity and population viability assessments
      alters conclusions regarding patch importance to connectivity and suggests higher
      metapopulation viability than when ignoring this hidden spatial scale. We argue
      that network modularity reveals critical meso-scales that are probably common in
      populations, providing a powerful means of identifying fundamental scales for
      biology and for conservation strategies aimed at recovering imperilled species. 

PMID- 24096938
TI  - Theoretical investigation of the electronic structure and quantum transport in
      the graphene-C(111) diamond surface system.
AB  - We investigate the interaction of a graphene monolayer with the C(111) diamond
      surface using ab initio density functional theory. To accommodate the lattice
      mismatch between graphene and diamond, the overlayer deforms into a wavy
      structure that binds strongly to the diamond substrate. The detached ridges of
      the wavy graphene overlayer behave electronically as free-standing polyacetylene
      chains with delocalized pi electrons, separated by regions containing only sp(3)
      carbon atoms covalently bonded to the (111) diamond surface. We performed quantum
      transport calculations for different geometries of the system to study how the
      buckling of the graphene layer and the associated bonding to the diamond
      substrate affect the transport properties. The system displays high carrier
      mobility along the ridges and a wide transport gap in the direction normal to the
      ridges. These intriguing, strongly anisotropic transport properties qualify the
      hybrid graphene-diamond system as a viable candidate for electronic nanodevices. 

PMID- 24096940
TI  - Controlled fabrication and photocatalytic properties of a three-dimensional ZnO
      nanowire/reduced graphene oxide/CdS heterostructure on carbon cloth.
AB  - A novel ZnO/reduced graphene oxide (RGO)/CdS heterostructure was successfully
      synthesized via a facile three-step solution method. RGO serves as an interlayer
      between ZnO nanowires and CdS quantum dots (QDs), which provides a high speed
      charge transfer channel, leading to an enhanced charge separation efficiency.
      Under UV light irradiation, the photocatalytic activity of the ZnO/RGO/CdS
      heterostructure is 4.0 times and 1.9 times as high as those of pure ZnO and
      ZnO/RGO, respectively. Under visible light irradiation, the ZnO/RGO/CdS
      heterostructure shows a dramatic visible light photocatalytic activity which is
      2.3 times higher than that of the ZnO/CdS photocatalyst. The photocurrent of the
      ZnO/RGO/CdS heterostructure under UV light irradiation was greatly enhanced and a
      photocurrent under visible light irradiation was observed. The enhanced
      photocatalytic activity and the extended light adsorption spectrum originate from
      the type-II ZnO/CdS band alignment and the introduction of RGO as a charge
      mediator. Our results might open up a promising way to develop novel and highly
      efficient RGO-based heterostructure photocatalysts. 

PMID- 24096939
TI  - Effects of dietary chromium picolinate and peppermint essential oil on growth
      performance and blood biochemical parameters of broiler chicks reared under heat
      stress conditions.
AB  - A study was conducted using 240 female day-old broiler chicks to evaluate the
      effects of dietary chromium picolinate (CrPic), peppermint essential oil
      (P.mint), or their combination on growth performance and blood biochemical
      parameters of female broiler chicks raised under heat stress conditions (HS, 23.9
      to 38  degrees C cycling). Average daily gain (ADG), average daily feed intake
      (ADFI), and feed conversion ratio (FCR) were obtained from 1 to 42 days of age.
      Furthermore, at the end of the experiment (day 42), birds were bled to determine
      some blood biochemical parameters and weighed for final body weight (BW). ADFI,
      ADG, and BW were not influenced significantly by dietary CrPic and P.mint
      (P>0.05). A significant interaction between dietary CrPic and P.mint on FCR
      (P=0.012) was detected. FCR significantly decreased in chicks fed the diet
      including both CrPic and P.mint compared with the CrPic group. Significant
      interaction between dietary P.mint and CrPic on serum concentrations of
      triglycerides, glucose, and albumin were observed (P<0.05), but the other
      measured blood biochemical parameters were not statistically affected by dietary
      treatments (P>0.05). The serum concentrations of glucose, triglycerides were
      decreased (P<0.05) in broilers fed the diet including both CrPic and P.mint.
      Plasma chromium (Cr) content increased significantly (P<0.05) in birds fed the
      CrPic-included diet compared with the control group (P<0.05). From the results of
      the present experiment it can be concluded that dietary supplementation with
      combined P.mint and CrPic could have beneficial effects on some blood biochemical
      parameters of female chicks reared under heat stress conditions.

PMID- 24096941
TI  - Forage and rangeland plants from uranium mine soils: long-term hazard to
      herbivores and livestock?
AB  - Metalliferous uranium mine overburden soils integrated into arable land or
      stabilized by perennial rangeland plants evoke concern about the quality of crops
      and the exposure of grazing and thereby soil-ingesting (wildlife) herbivores to
      heavy metals (HM) and radionuclides. In a 2-year trial, thirteen annual and
      perennial forage and rangeland plants were thus potted on, or taken from,
      cultivated field soil of a metalliferous hot spot near Ronneburg (Germany). The
      content of soil and shoot tissues in 20 minerals was determined by ICP-MS to
      estimate HM (and uranium) toxicities to grazing animals and the plants
      themselves, and to calculate the long-term persistence of the metal toxicants
      (soil clean-up times) from the annual uptake rates of the plants. On Ronneburg
      soil elevated in As, Cd, Cu, Mn, Pb, U, and Zn, the shoot mineral content of all
      test plants remained preferentially in the range of "normal plant concentrations"
      but reached up to the fourfold to sixfold in Mn, Ni, and Zn, the 1.45- to 21.5
      fold of the forage legislative limit in Cd, and the 10- to 180-fold of common
      herb concentrations in U. Shoot and the calculated root concentrations in Cd, Cu,
      Ni, and Zn accounted for phytotoxic effects at least to grasses and cereals.
      Based on WHO PTWI values for the tolerable weekly human Cd and Pb intake, the
      expanded Cd and Pb limits for forage, and reported rates of hay, roots, and
      adhering-soil ingestion, the tolerable daily intake rates of 0.65/11.6 mg in
      Cd/Pb by a 65 kg herbivore would be surpassed by the 11- to 27/0.7- to 4.7-fold
      across the year, with drastic consequences for winter-grazing and thereby high
      rates of roots and soil-ingesting animals. The daily intake of 5.3-31.5 mg of the
      alpha radiation emitter, U, may be less disastrous to short-lived herbivores. The
      annual phytoextraction rates of critical HM by the tested excluder crops indicate
      that hundreds to thousands of years are necessary to halve the HM and (long
      lived) radionuclide load of Ronneburg soil, provided the herbage is harvested at
      all. It is concluded that the content in Cd/As, Cd, and Cu exclude
      herbage/Ronneburg soil from the commercial use as forage or pasture land soil for
      incalculable time spans. Caution is required, too, with the consumption of game.

PMID- 24096942
TI  - Understanding the salinity issue of coal mine spoils in the context of salt
      cycle.
AB  - Coal mine spoils (CMSs), the solid wastes originated from the rock formations and
      soil cover overlying or interbedded with coal seams, are a worldwide
      environmental management challenge. Previous studies have shown that salinity is
      of most concern among the CMSs' environmental impacts, especially in Australia.
      With increasing concerns from both the governments and communities, there is a
      real need for the coal mining industry to understand the source, dynamics and
      management options of CMS salinity. We reviewed the general properties of CMSs
      from coal mine sites worldwide and the current understanding of the CMS salinity,
      which are in a limited number of available published reports. Properties (e.g.,
      pH, electrical conductivity and hydraulic conductivity) of studied CMSs varied
      largely due to its complex lithological origination. A conceptual model was
      proposed to illustrate the origin, dispersion paths and transformations dynamics
      of salts in spoils, taking the scenario of a coal mine in Australia as an
      example. The major factors governing the salt dynamics in CMSs are summarized as
      mineral weatherability and salt leachability of the spoils. Management of CMS
      salinity is still a vague area awaiting more extensive studies. Three topics
      related to the management were explored in the review, which are pre-mining
      planning, spatial variability of spoil properties and remediation including
      electrokinetics and phytoremediation. Particularly, based on the geological
      classification of CMSs and the leachate chemistry of spoils of various sources, a
      clear relationship between salinity and geounits was established. This
      association has a potential application in pre-mining planning for the management
      of salinity from coal mine spoils. 

PMID- 24096943
TI  - Polarized linewidth-controllable double-trapping electromagnetically induced
      transparency spectra in a resonant plasmon nanocavity.
AB  - Surface plasmons with ultrasmall optical mode volume and strong near field
      enhancement can be used to realize nanoscale light-matter interaction. Combining
      surface plasmons with the quantum system provides the possibility of nanoscale
      realization of important quantum optical phenomena, including the
      electromagnetically induced transparency (EIT), which has many applications in
      nonlinear quantum optics and quantum information processing. Here, using a custom
      designed resonant plasmon nanocavity, we demonstrate polarized position-dependent
      linewidth-controllable EIT spectra at the nanoscale. We analytically obtain the
      double coherent population trapping conditions in a double-Lambda quantum system
      with crossing damping, which give two transparent points in the EIT spectra. The
      linewidths of the three peaks are extremely sensitive to the level spacing of the
      excited states, the Rabi frequencies and detunings of pump fields, and the
      Purcell factors. In particular the linewidth of the central peak is exceptionally
      narrow. The hybrid system may have potential applications in ultra-compact
      plasmon-quantum devices. 

PMID- 24096945
TI  - Research frontiers in the chemistry of Criegee intermediates and tropospheric
      ozonolysis.
AB  - The chemistry of carbonyl oxides, known as Criegee intermediates, is central to
      many aspects of tropospheric chemistry. For decades it has been known that these
      reactive species, whose electronic structure contains zwitterionic and biradical
      character, are formed in the ozonolysis of alkenes. However it is only recently
      that direct measurements of their reaction kinetics have become possible. In this
      perspective we describe the most recent progress in understanding the reactivity
      of these historically elusive molecules, explore the atmospheric chemistry
      implications of new experimental discoveries, and propose important new areas for
      investigation. 

PMID- 24096944
TI  - Background diet and fat type alters plasma lipoprotein response but not aortic
      cholesterol accumulation in F1B Golden Syrian hamsters.
AB  - Dietary modification alters plasma lipoprotein profiles and atherosclerotic
      lesion progression in humans and some animal models. Variability in response to
      diet induced atherosclerosis has been reported in hamsters. Assessed was the
      interaction between background diet composition and dietary fat type on aortic
      cholesterol accumulation, lipoprotein profiles, hepatic lipids and selected
      genes. F1B Golden Syrian hamsters (20/group) were fed (12 weeks) semi-purified or
      non-purified diets containing either 10 % (w/w) coconut oil or safflower oil and
      0.15 % (w/w) cholesterol. The non-purified diets relative to semi-purified diets
      resulted in significantly higher TC (72 % [percent difference] and 38 %, coconut
      oil and safflower oil, respectively) and nHDL-C (84 and 61 %, coconut oil and
      safflower oil, respectively), and lower HDL-C (-47 and -45 %, coconut oil and
      safflower oil, respectively) concentrations. Plasma triacylglycerol
      concentrations in the hamsters fed the non-purified coconut oil-supplemented
      diets were three- to fourfold higher than non-purified safflower oil
      supplemented, and both semi-purified diets. With the exception of HDL-C, a
      significant effect of fat type was observed in TC, nHDL-C and triacylglycerol
      (all P < 0.05) concentrations. Regardless of diet induced differences in
      lipoprotein profiles, there was no significant effect on aortic cholesterol
      accumulation. There was an inverse relationship between plasma nHDL-C and
      triacylglycerol, and hepatic cholesteryl ester content (P < 0.001). Diet induced
      differences in hepatic gene transcription (LDL receptor, apoB-100, microsomal
      transfer protein) were not reflected in protein concentrations. Although hamsters
      fed non-purified and/or saturated fatty acid-supplemented diets had more
      atherogenic lipoprotein profiles compared to hamsters fed semi-purified and/or
      polyunsaturated fatty acid-supplemented diets these differences were not
      reflected in aortic cholesterol accumulation.

PMID- 24096946
TI  - Mediastinoscopy: trends and practice patterns in the United States.
AB  - OBJECTIVES: Historically, mediastinoscopy has been the gold standard for the
      staging of lung cancer. A practice gap exists as the result of a variation in
      knowledge concerning current trends and practice patterns of mediastinoscopy
      usage. In addition, there are regional variations in practice-based learning and
      patient care. Lessons learned during surgeries performed on patients with lung
      cancer and other advances such as positron emission tomography and endobronchial
      ultrasound could be universally applied to improve surgeons' management of
      patient care. The purpose of this study was to assess contemporary practices in
      the staging of lung cancer. METHODS: We queried the Society of Thoracic Surgeons
      National Database for data regarding mediastinoscopy usage, yield, and variation,
      both by year and region. RESULTS: Cases with mediastinoscopy, as a percentage of
      all cases performed in the database, have significantly decreased from 14.6% in
      2006 to 11.4% in 2010 (P < 0.001). The 5-year median rate of mediastinoscopy in
      lung cancer patients at 163 centers was 15.3% (interquartile range 5.2%-31.7%),
      indicating significant variation among centers. The overall median center rate
      also decreased over time from 21.4% (2006) to 10.0% (2010). CONCLUSIONS: With
      advances in minimally invasive procedures and imaging, mediastinoscopy usage has
      declined significantly. Our findings are likely to be relevant to both clinical
      practice and practice guidelines.

PMID- 24096947
TI  - Endoscopy after acute myocardial infarction: an evaluation of safety.
AB  - OBJECTIVES: Upper gastrointestinal bleeding in the setting of acute myocardial
      infarction (MI) has substantial morbidity and mortality. Several studies have
      been performed on the safety of esophagogastroduodenoscopy (EGD) after MI;
      however, these studies vary in definitions and results. We evaluated the safety
      and effect of EGD in patients with acute MI in a tertiary center. METHODS: A
      retrospective, single tertiary-care center study was undertaken of 87 patients
      who underwent EGD within 30 days of an acute MI between January 2001 and March
      2012. Type of MI (ST segment elevation MI [STEMI] and non-ST segment elevation MI
      [NSTEMI]), peak troponin I, time from MI to EGD, Acute Physiology and Chronic
      Health Evaluation (APACHE) II score at EGD, cardiac catheterization before EGD,
      and medical complications within 24 hours of EGD were noted. Medical
      complications were defined as major complications (death, life-threatening
      arrhythmias) and minor complications (chest pain, abnormal vital signs, or minor
      arrhythmias). RESULTS: Eighty-seven patients underwent EGD within 30 days of
      having an MI. No major complications were observed. Minor complications occurred
      in 27 of 87 patients (31.0%), including mild hypotension, mild bradycardia, or
      increased chest pain. Patients with STEMI demonstrated statistically significant
      quicker endoscopy (P = 0.01) and were more likely to undergo cardiac
      catheterization in advance of EGD (P < 0.01) than those with NSTEMI. No
      statistically significant differences were noted for peak troponin I (P = 0.21),
      APACHE II score at EGD (P = 0.55), or minor complications (P = 0.08) among
      patients with STEMI versus NSTEMI. Cardiac catheterization before EGD did not
      seem to affect results. Patients with APACHE II scores >16 experienced more minor
      complications (P = 0.02). CONCLUSIONS: EGD appears relatively safe for the
      diagnosis and management of upper gastrointestinal bleeding in patients with
      acute MI.

PMID- 24096948
TI  - Home food environment, dietary intake, and weight among overweight and obese
      children in Southern Appalachia.
AB  - OBJECTIVES: This study examined the relation of multiple aspects of the home food
      environment to dietary intake and body weight among overweight and obese children
      in southern Appalachia. METHODS: The study used baseline data from a cluster
      randomized controlled trial, Parent-Led Activity and Nutrition for Healthy
      Living, evaluating a parent-mediated approach to treating child overweight and
      obesity in the primary care setting in southern Appalachia. Sixty-seven children
      ages 5 to 11 years were recruited from four primary care clinics. Multiple linear
      regression was used to estimate the relation between multiple aspects of the home
      food environment to dietary intake (fruit and vegetable intake, fat and sweets
      intake), and standardized body mass index (zBMI), adjusted for baseline family
      characteristics (education, smoking status during the past month, BMI) and child
      characteristics (sex, age, Medicaid/TennCare). RESULTS: Findings showed greater
      parental restriction and pressure in feeding were associated with greater fruit
      and vegetable intake in children (beta = 0.33, beta = 0.30, respectively; both P
      < 0.05). The availability of chips and sweets in a child's home and parental
      inappropriate modeling of eating were associated with an increased risk for
      consumption of fats and sweets by children (beta = 0.47, beta = 0.54,
      respectively; both P < 0.01). Parental monitoring of the child's eating was
      associated with a reduced risk for fat and sweets intake (beta = -0.24; P <
      0.01). Finally, parental responsibility for feeding the child was associated with
      lower zBMI (beta = -0.20; P < 0.05). CONCLUSIONS: The home food environment,
      including food availability and parenting behaviors, was associated with
      overweight and obese children's dietary intake and weight. This study adds to
      evidence suggesting that programs aimed at improving overweight and obese
      children's eating patterns may target both aspects of the physical home
      environment and parental behaviors surrounding eating.

PMID- 24096949
TI  - Perceptions and attitudes about preexposure prophylaxis among seronegative
      partners and the potential of sexual disinhibition.
AB  - OBJECTIVES: Preexposure prophylaxis (PrEP) is a promising strategy to prevent
      human immunodeficiency virus (HIV) infection, especially among high-risk
      individuals such as seronegative partners; however, many caveats such as the
      potential risk of sexual disinhibition and noncompliance need to be considered.
      We explored the sociodemographic and behavioral factors associated with the
      adoption of PrEP among HIV seronegative men who have sex with men and
      heterosexual partners. METHODS: A prepiloted self-administered survey was
      conducted among seronegative partners in a Ryan White HIV/AIDS Clinic in South
      Carolina from 2010 to 2011. Bivariate and multivariable analyses were used to
      explore the data. RESULTS: The survey was completed by 89 seronegative partners.
      The median age was 42 years (interquartile range 32-50) and a majority was men
      (56%), black (70%), and heterosexual (74%). A majority (94%) was willing to use
      PrEP if available; however, 26% of subjects suggested that they would be more
      likely to have unprotected sex with an HIV-positive partner while using PrEP, and
      27% suggested that it would be difficult to take a daily dose of PrEP and
      consistently use condoms. The multivariable results suggest that the belief that
      a condom is no longer needed while taking PrEP was more likely among those who
      did not use a condom during their last sexual intercourse (adjusted odds ratio
      7.45; 95% confidence interval 1.57-35.45) and among those with a higher HIV
      knowledge score (adjusted odds ratio 0.43; 95% confidence interval 0.23-0.78).
      CONCLUSIONS: Overall, these results suggest high acceptability of PrEP among
      seronegative partners to lower the risk of HIV transmission; however, there is a
      substantial risk of sexual disinhibition and noncompliance while using PrEP that
      may be reduced by ongoing education.

PMID- 24096950
TI  - Sharpening the tandem walking test for screening peripheral neuropathy.
AB  - OBJECTIVE: Few tests of functional motor behavior are useful for rapidly
      screening people for lower extremity peripheral neuropathy. The goal of this
      study was to improve the widely used tandem walking (TW) test. METHODS: We tested
      "normal" (control) adult and ambulatory patients with peripheral neuropathy (PN)
      with their eyes open and eyes closed while they performed TW on industrial
      carpeting in sock-covered feet. Each subject wore a torso-mounted inertial motion
      unit to measure kinematic data. The data of subjects with PN also were compared
      with historical data on patients with vestibular impairments. RESULTS: The normal
      and PN groups differed significantly on TW and on the number of steps completed.
      PN and vestibular impairments data also differed significantly on both visual
      conditions. Kinematic data showed that patients with PN were more unstable than
      normal patients in the group. For the number of steps taken during the eyes open
      condition, receiver operating characteristic (ROC) values were only 0.81 and for
      the number of steps taken during the eyes closed condition, ROC values were 0.88.
      Although not optimal, this ROC value is better. Sensitivity and specificity at a
      cutoff of two steps were 0.81 and 0.92, respectively, and at a cutoff of three
      steps were 0.86 and 0.75, respectively. ROC values for kinematic data were <0.8,
      and when combined with the ROC value for the number of steps, the total ROC value
      did not improve appreciably. CONCLUSIONS: Although not ideal for screening
      patients who may have PN, counting the number of steps during TW is a quick and
      useful clinical test. TW is most sensitive to patients with PN when they are
      tested with eyes closed.

PMID- 24096951
TI  - Polycystic ovary syndrome in adolescents: (women's health series).
AB  - Polycystic ovary syndrome is the single most common endocrine abnormality of
      women of reproductive age and is a leading cause of female infertility. Common
      clinical features include hirsutism, various ovarian abnormalities, obesity, and
      insulin resistance. Expert consensus recommendations on diagnostic criteria vary,
      but the most recent focus on the presence of clinical features of
      hyperandrogenism, hyperandrogenemia, polycystic ovaries, and ovulatory and
      menstrual dysfunction to the exclusion of alternative diagnoses. In adolescence,
      diagnosis is more difficult because of the frequent presence of individual
      clinical findings in otherwise "normal" individuals. Laboratory tests and pelvic
      ultrasound are necessary to confirm polycystic ovary syndrome and exclude other
      disorders that may mimic this syndrome. Treatment is centered on the clinical
      manifestations and should be initiated early to prevent/limit long-term
      complications, including the metabolic syndrome, diabetes, endometrial carcinoma,
      and infertility. 

PMID- 24096952
TI  - Acute sinusitis.
AB  - Sinusitis is a common patient complaint that carries with it a large economic
      burden. It is one of the most common reasons patients visit their primary care
      physician. Acute bacterial rhinosinusitis (ABRS) can be distinguished from other
      forms of rhinosinusitis based on symptom duration of <4 weeks in a patient with
      purulent rhinorrhea associated with facial pain or pressure. Native upper
      aerodigestive tract bacteria are the most common etiologic agents. Treatment of
      ABRS is targeted primarily at symptom improvement. Amoxicillin can be used based
      on the clinical scenario and patient comorbidities. Computed tomographic scans
      are reserved for complicated presentations or when there is concern for
      intracranial extension or other complications. A systematic approach to ABRS will
      allow for improved patient quality of life and a decreased overall economic
      burden of this common entity. 

PMID- 24096953
TI  - Lung cancer in women.
AB  - Lung cancer is the deadliest cancer in women. In the last decade, the first
      measurable decline in disease-related mortality has occurred and in the last 5
      years, the first decline in lung cancer incidence in women in the United States
      has been reported. Five-year survival rates are much higher in early-stage
      disease, making effective screening a priority. Data on screening with low-dose
      computed tomography are controversial; existing guidelines are not sex specific
      and recommend testing only for patients at high risk for the disease. Although
      cigarette smoking remains the predisposing factor that is most often associated
      with tumor development, the advent of molecularly targeted therapy and the
      growing evidence that susceptible targets are more prevalent in never-smoking
      women have brought more attention to this particular subpopulation. Studies of
      both surgery and systemic therapy suggest that not only never-smoking women but
      also women overall experience better outcomes than men. Identifying all of the
      factors contributing to these sex differences presents us with an opportunity to
      identify potentially a distinct tumor biology in women who would warrant a
      distinct personalized treatment approach. 

PMID- 24096954
TI  - Acute fatty liver of pregnancy.
AB  - Acute fatty liver of pregnancy is a rare but serious and potentially fatal
      complication of pregnancy. It typically presents in the third trimester with
      microvesicular fatty infiltration of the liver and can lead to multiorgan failure
      and death. Differentiation from hemolysis-elevated liver enzymes-low platelets
      syndrome can guide management. A high index of suspicion is necessary in the
      appropriate clinical setting to identify clinical manifestations and
      complications and manage them appropriately. In severe cases, prompt delivery can
      be lifesaving for the mother and fetus. Liver transplantation remains
      controversial and must be considered individually. Defects in fatty acid
      oxidation secondary to various enzymatic deficiencies have been associated with
      acute fatty liver of pregnancy. Women or couples with known defects in fatty acid
      oxidation and women with a history of previous liver disease during pregnancy or
      sudden death of a child within the first 2 years of life should be assessed for a
      defect in fatty acid oxidation and monitored carefully. Our review summarizes the
      current knowledge in pathophysiology, diagnostic approach and management of this
      disorder. 

PMID- 24096955
TI  - Considerations in women with hypertension.

PMID- 24096956
TI  - Authors' response.

PMID- 24096957
TI  - Behavioral medicine in the 21st century: transforming "the Road Less Traveled"
      into the "American Way of Life".
AB  - INTRODUCTION: A key objective of this paper is to describe some major challenges
      and opportunities facing the behavioral medicine field in the current decade.
      Amidst current US statistics that present a sobering image of the nation's
      health, there have been a number of notable achievements in the behavioral
      medicine field that span the scientific/health continuum. However, many of these
      achievements have received little notice by the public and decision makers.
      METHODS: A case is presented for the potential of scientific narrative for
      presenting behavioral medicine evidence in ways that engage attention and compel
      action. Additional areas for behavioral medicine engagement include expanding
      interdisciplinary connections into new arenas, continuing the growth of
      activities involving emerging technologies, building international connections,
      and engaging with policy. CONCLUSION: Finally, the fundamental importance of an
      integrated behavioral medicine field that plays an active role in supporting and
      advancing its members and the field as a whole is discussed.

PMID- 24096958
TI  - Heterologous expression of natural product biosynthetic gene clusters in
      Streptomyces coelicolor: from genome mining to manipulation of biosynthetic
      pathways.
AB  - Heterologous gene expression is one of the main strategies used to access the
      full biosynthetic potential of actinomycetes, as well as to study the metabolic
      pathways of natural product biosynthesis and to create unnatural pathways.
      Streptomyces coelicolor A3(2) is the most studied member of the actinomycetes,
      bacteria renowned for their prolific capacity to synthesize a wide range of
      biologically active specialized metabolites. We review here the use of strains of
      this species for the heterologous production of structurally diverse actinomycete
      natural products. 

PMID- 24096959
TI  - Modeling one complete versus triplicate analyses in low template DNA typing.
AB  - There are generally two strategies for low template DNA typing: the complete
      strategy, which uses all available DNA in a single PCR and subsequent typing, and
      the consensus strategy, in which the biological sample is divided into two or
      more aliquots and the genotype profile is determined by consensus from these
      "replicates." In this study, the consensus and complete strategies are compared
      by a statistical approach in terms of the accuracy of obtaining the correct
      genotype at a single locus for single source samples. Logistic models were
      employed to describe the allele drop-out and drop-in events. The parameters of
      the models were estimated with empirical or hypothetical data. The probabilities
      of obtaining the true genotype and the chances to observe drop-out and drop-in
      alleles were estimated and compared for both strategies. Consistent with a
      previous experimental study, this study found that, with relatively high input
      DNA (e.g., >= 100 pg), the complete strategy performs better than the consensus
      strategy to obtain the true genotype and the complete strategy will display less
      dropped out alleles. The consensus strategy had less drop-in alleles for <= 100
      pg DNA samples. Moreover, the limitations of the logistic models were discussed.
      Ideal models with better fit of empirical data approximating casework conditions
      were proposed for future studies.

PMID- 24096960
TI  - Role of electrical storm as a mortality and morbidity risk factor and its
      clinical predictors: a meta-analysis.
AB  - AIMS: Electrical storm (ES) is a devastating and life-threatening event in
      clinical practice, but its real weight as a risk factor and its clinical
      predictors remain unclear. Our objective was to evaluate ES as a mortality and
      morbidity risk factor and to define the clinical variables associated with ES.
      METHODS AND RESULTS: The meta-analysis was performed according to the PRISMA
      guidelines. At the end of the selection process, 13 studies were collected and
      included in the quantitative analysis. Mortality and morbidity due to ES were
      assessed. The most acknowledged ES predictors were taken into account in separate
      sub-analyses. The whole cohort included 5912 patients (857 with ES). Risk of
      death was increased in the ES group [risk ratio (RR) 3.15; 95% confidence
      interval (CI) 2.22-4.48]. Electrical storm was also associated with increased
      composite risk of all-cause death, cardiac transplantation, and hospitalization
      for acute heart failure (RR 3.39; 95% CI 2.31-4.97). These results were confirmed
      by comparing the ES group with patients with or without previous unclustered
      episodes of ventricular arrhythmias. Moreover, implantable cardioverter
      defibrillator (ICD) for secondary prevention, lower ejection fraction,
      monomorphic ventricular tachycardia as triggering arrhythmia, and class I anti
      arrhythmic drugs therapy were all associated with ES. CONCLUSION: Electrical
      storm is a strong mortality risk factor and it is associated with an increased
      combined risk of death, heart transplantation, and hospitalization for heart
      failure. Implantable cardioverter-defibrillator for secondary prevention,
      monomorphic ventricular tachycardia as triggering arrhythmia, lower ejection
      fraction, and class I anti-arrhythmic drugs therapy are all associated with ES
      and could be used to define specific populations with higher risk to develop ES.

PMID- 24096961
TI  - Radiographic findings of a persistent left-sided superior vena cava.

PMID- 24096962
TI  - Evidence for a role of sterol 27-hydroxylase in glucocorticoid metabolism in
      vivo.
AB  - The intracellular availability of glucocorticoids is regulated by the enzymes
      11beta-hydroxysteroid dehydrogenase 1 (HSD11B1) and 11beta-hydroxysteroid
      dehydrogenase 2 (HSD11B2). The activity of HSD11B1 is measured in the urine based
      on the (tetrahydrocortisol+5alpha-tetrahydrocortisol)/tetrahydrocortisone
      ((THF+5alpha-THF)/THE) ratio in humans and the (tetrahydrocorticosterone+5alpha
      tetrahydrocorticosterone)/tetrahydrodehydrocorticosterone ((THB+5alpha-THB)/THA)
      ratio in mice. The cortisol/cortisone (F/E) ratio in humans and the
      corticosterone/11-dehydrocorticosterone (B/A) ratio in mice are markers of the
      activity of HSD11B2. In vitro agonist treatment of liver X receptor (LXR) down
      regulates the activity of HSD11B1. Sterol 27-hydroxylase (CYP27A1) catalyses the
      first step in the alternative pathway of bile acid synthesis by hydroxylating
      cholesterol to 27-hydroxycholesterol (27-OHC). Since 27-OHC is a natural ligand
      for LXR, we hypothesised that CYP27A1 deficiency may up-regulate the activity of
      HSD11B1. In a patient with cerebrotendinous xanthomatosis carrying a loss-of
      function mutation in CYP27A1, the plasma concentrations of 27-OHC were
      dramatically reduced (3.8 vs 90-140 ng/ml in healthy controls) and the urinary
      ratios of (THF+5alpha-THF)/THE and F/E were increased, demonstrating enhanced
      HSD11B1 and diminished HSD11B2 activities. Similarly, in Cyp27a1 knockout (KO)
      mice, the plasma concentrations of 27-OHC were undetectable (<1 vs 25-120 ng/ml
      in Cyp27a1 WT mice). The urinary ratio of (THB+5alpha-THB)/THA was fourfold and
      that of B/A was twofold higher in KO mice than in their WT littermates. The
      (THB+5alpha-THB)/THA ratio was also significantly increased in the plasma, liver
      and kidney of KO mice. In the liver of these mice, the increase in the
      concentrations of active glucocorticoids was due to increased liver weight as a
      consequence of Cyp27a1 deficiency. In vitro, 27-OHC acts as an inhibitor of the
      activity of HSD11B1. Our studies suggest that the expression of CYP27A1 modulates
      the concentrations of active glucocorticoids in both humans and mice and in
      vitro. 

PMID- 24096963
TI  - Alendronate promotes bone formation by inhibiting protein prenylation in
      osteoblasts in rat tooth replantation model.
AB  - Bisphosphonates (BPs) are a major class of antiresorptive drug, and their
      molecular mechanisms of antiresorptive action have been extensively studied.
      Recent studies have suggested that BPs target bone-forming cells as well as bone
      resorbing cells. We previously demonstrated that local application of a nitrogen
      containing BP (N-BP), alendronate (ALN), for a short period of time increased
      bone tissue in a rat tooth replantation model. Here, we investigated cellular
      mechanisms of bone formation by ALN. Bone histomorphometry confirmed that bone
      formation was increased by local application of ALN. ALN increased proliferation
      of bone-forming cells residing on the bone surface, whereas it suppressed the
      number of tartrate-resistant acid phosphatase (TRAP)-positive osteoclasts in
      vivo. Moreover, ALN treatment induced more alkaline phosphatase-positive and
      osteocalcin-positive cells on the bone surface than PBS treatment. In vitro
      studies revealed that pulse treatment with ALN promoted osteocalcin expression.
      To track the target cells of N-BPs, we applied fluorescence-labeled ALN (F-ALN)
      in vivo and in vitro. F-ALN was taken into bone-forming cells both in vivo and in
      vitro. This intracellular uptake was inhibited by endocytosis inhibitors.
      Furthermore, the endocytosis inhibitor dansylcadaverine (DC) suppressed ALN
      stimulated osteoblastic differentiation in vitro and it suppressed the increase
      in alkaline phosphatase-positive bone-forming cells and subsequent bone formation
      in vivo. DC also blocked the inhibition of Rap1A prenylation by ALN in the
      osteoblastic cells. These data suggest that local application of ALN promotes
      bone formation by stimulating proliferation and differentiation of bone-forming
      cells as well as inhibiting osteoclast function. These effects may occur through
      endocytic incorporation of ALN and subsequent inhibition of protein prenylation. 

PMID- 24096964
TI  - Pre- and postnatal nutrition in sheep affects beta-cell secretion and
      hypothalamic control.
AB  - Maternal undernutrition increases the risk of type 2 diabetes and metabolic
      syndrome later in life, particularly upon postnatal exposure to a high-energy
      diet. However, dysfunctions of, for example, the glucose-insulin axis are not
      readily detectable by conventional tests early in life, making it difficult to
      identify individuals at risk. Thus, other methods are required. We hypothesised
      that prenatally undernourished individuals (but not postnatally overnourished
      ones) are adapted to a life with limited food availability, which would be
      evident under conditions reflecting starvation, stress and short-term abundance
      of food. In this study, twin-pregnant sheep were fed diets meeting 100% (NORM) or
      50% (LOW) of energy and protein requirements during the last trimester. Twin
      offspring were fed either a normal moderate (CONV) diet or a high-carbohydrate
      high-fat (HCHF) diet from 3 days to 6 months of age (approximately puberty) and
      the same moderate diet thereafter until 2 years of age (young adulthood; only
      females), resulting in four groups: NORM-CONV, LOW-CONV, NORM-HCHF and LOW-HCHF.
      At the age of 6 months and 2 years respectively, they were subjected to fasting
      and propionate (nutrient abundance) and adrenalin challenges. At 6 months of age,
      postnatal HCHF diet exposure caused metabolic alterations, reflecting
      hypertriglyceridaemia and altered pancreatic beta-cell secretion. Irrespective of
      postnatal diet, prenatal undernutrition was found to be associated with
      unexpected endocrine responses of leptin, IGF1 and cortisol during fasting (lack
      of or the opposite response compared with the controls) in 2-year-old adults. In
      conclusion, a HCHF diet interfered with beta-cell function, whereas maternal
      undernutrition did not lead to any changes in the LOW offspring, except to
      abnormal hormone responses, suggesting that fetal programming interferes with
      hypothalamic integration of important endocrine axis. 

PMID- 24096965
TI  - Growth hormone and Klotho.
AB  - Acromegaly is characterized by excessively high GH and IGF1 levels. Recent data
      suggest that soluble Klotho (sKlotho) is also elevated in patients with active
      acromegaly. sKlotho decreases towards normal following removal of the GH
      producing pituitary adenoma. The Klotho gene was identified in mice following its
      accidental disruption by ectopic DNA. It is an ageing suppressor gene of
      restricted expression (mainly in kidneys, brain, and parathyroid and pituitary
      glands) encoding a transmembrane protein, mKlotho. mKlotho serves as a co
      receptor in fibroblast growth factor 23 (FGF23) signalling. FGF23 promotes
      urinary phosphate excretion and inhibits the synthesis of calcitriol. The
      ectodomain of mKlotho is enzymatically released to result in a humoral factor,
      sKlotho, which exerts systemic effects (on ion channels and signalling pathways),
      possibly by working as an enzyme that modifies glycans of cell surface
      glycoproteins. GH enhances renal phosphate reabsorption and calcitriol
      production, i.e. exerts effects in the proximal tubule opposing those attributed
      to mKlotho, and attenuates calciuria in the distal tubule similar to sKlotho.
      sKlotho can be measured in extracellular fluids (serum, urine and cerebrospinal
      fluid (CSF)) by an ELISA. In line with predominant expression of Klotho in
      kidneys and choroid plexus, concentrations of sKlotho are particularly high in
      urine and CSF. Determination of sKlotho in serum and urine (both presumably
      reflecting GH action on the kidneys) could be used as a supplementary tool in the
      diagnosis and follow-up of patients with acromegaly. The question arises whether
      GH exerts selected actions via modifying activities of Klotho. 

PMID- 24096966
TI  - Spoof research paper is accepted by 157 journals.

PMID- 24096967
TI  - Semi-mechanistic modelling of the analgesic effect of gabapentin in the formalin
      induced rat model of experimental pain.
AB  - PURPOSE: The formalin-induced rat model of nociception involves moderate
      continuous pain. Formalin-induced pain results in a typical repetitive flinching
      behaviour, which displays a biphasic pattern characterised by peaks of pain. Here
      we described the time course of pain response and the analgesic effect of
      gabapentin using a semi-mechanistic modelling approach. METHODS: Male Sprague
      Dawley rats received gabapentin (10-100 mg/kg) or placebo 1 h prior to the
      formalin injection, as per standard protocol. A reduction in the frequency of the
      second peak of flinching was used as a behavioural measure of gabapentin-mediated
      anti-nociception. The flinching response was modelled using a mono-exponential
      function to characterise the first peak and an indirect response model with a
      time variant synthesis rate for the second. PKPD modelling was performed using a
      population approach in NONMEM v.7.1.2. RESULTS: The time course of the biphasic
      response was adequately described by the proposed model, which included separate
      expressions for each phase. Gabapentin was found to reversibly decrease, but not
      suppress the flinching frequency of the second response peak only. The mean IC50
      estimate was 7,510 ng/ml, with relative standard error (RSE%) of 40%.
      CONCLUSIONS: A compartmental, semi-mechanistic model provides the basis for
      further understanding of the formalin-induced flinching response and consequently
      to better characterisation of the properties of gabapentin, such as the potency
      in individual animals. Moreover, despite high exposure levels, model predictions
      show that gabapentin does not completely suppress behavioural response in the
      formalin-induced pain model.

PMID- 24096968
TI  - Clinical Pharmacogenetics Implementation Consortium (CPIC) guidelines for IFNL3
      (IL28B) genotype and PEG interferon-alpha-based regimens.
AB  - Pegylated interferon-alpha (PEG-IFN-alpha or PEG-IFN 2a and 2b)- and ribavirin
      (RBV)-based regimens are the mainstay for treatment of hepatitis C virus (HCV)
      genotype 1. IFNL3 (IL28B) genotype is the strongest baseline predictor of
      response to PEG-IFN-alpha and RBV therapy in previously untreated patients and
      can be used by patients and clinicians as part of the shared decision-making
      process for initiating treatment for HCV infection. We provide information
      regarding the clinical use of PEG-IFN-alpha- and RBV-containing regimens based on
      IFNL3 genotype. 

PMID- 24096970
TI  - Diversity of the human LILRB3/A6 locus encoding a myeloid inhibitory and
      activating receptor pair.
AB  - Leukocyte immunoglobulin-like receptor (LILR)B3 and LILRA6 represent a pair of
      inhibitory/activating receptors with identical extracellular domains and unknown
      ligands. LILRB3 can mediate inhibitory signaling via immunoreceptor tyrosine
      based inhibition motifs in its cytoplasmic tail whereas LILRA6 can signal through
      association with an activating adaptor molecule, FcRgamma, which bears a
      cytoplasmic tail with an immunoreceptor tyrosine-based activation motif. The
      receptors are encoded by two highly polymorphic neighboring genes within the
      leukocyte receptor complex on human chromosome 19. Here, we report that the two
      genes display similar levels of single nucleotide polymorphisms with the majority
      of polymorphic sites being identical. In addition, the LILRA6 gene exhibits copy
      number variation (CNV) whereas LILRB3 does not. A screen of healthy Caucasians
      indicated that 32 % of the subjects possessed more than two copies of LILRA6,
      whereas 4 % have only one copy of the gene per diploid genome. Analysis of mRNA
      expression in the major fractions of PBMCs showed that LILRA6 is primarily
      expressed in monocytes, similarly to LILRB3, and its expression level correlates
      with copy number of the gene. We suggest that the LILRA6 CNV may influence the
      level of the activating receptor on the cell surface, potentially affecting
      signaling upon LILRB3/A6 ligation. 

PMID- 24096971
TI  - Gender differences and a school-based obesity prevention program in Argentina: a
      randomized trial.
AB  - OBJECTIVE: To evaluate the impact of a school-based obesity prevention program
      that seeks to change food intake among students at schools in Rosario, Argentina.
      METHODS: This was a prospective study involving 405 children 9-11 years of age at
      six schools in the poor areas of Rosario, Argentina, in May-October 2008. After
      matching for socioeconomic status, schools were selected by simple randomization;
      participants were assessed at baseline (T1) and again 6 months later, after
      completion of the intervention (T2). The program focused on increasing the
      children's knowledge of healthy nutrition and exercise through four workshops;
      educating the parents/caregivers; and offering healthy options at the school
      snack bar. The main outcome measures were the children's intake of healthy and
      unhealthy foods (assessed with a weekly food frequency questionnaire) and their
      body mass index (BMI). RESULTS: Of the 387 children assessed at T1, 369 were
      reassessed at T2 (205 intervention; 164 control). Girls at the schools where the
      intervention occurred increased their intake of three of the five healthy food
      items promoted by the program (fruits, vegetables, low-sugar cereals).
      Statistical significance was reached for skim milk (P = 0.03) and for pure orange
      juice (P = 0.05). Boys of both the intervention and control groups failed to
      improve their intake of healthy foods, but those of the intervention arm
      significantly reduced their intake of hamburgers and hot dogs (P = 0.001).
      CONCLUSIONS: Girls were more amenable to improving their dietary intake. Overall,
      the program was more likely to increase consumption of healthy food than to
      decrease intake of unhealthy foods. Gender differences should be taken into
      account when designing preventive interventions.

PMID- 24096969
TI  - Characterization of statin dose response in electronic medical records.
AB  - Efforts to define the genetic architecture underlying variable statin response
      have met with limited success, possibly because previous studies were limited to
      effect based on a single dose. We leveraged electronic medical records (EMRs) to
      extract potency (ED50) and efficacy (Emax) of statin dose-response curves and
      tested them for association with 144 preselected variants. Two large biobanks
      were used to construct dose-response curves for 2,026 and 2,252 subjects on
      simvastatin and atorvastatin, respectively. Atorvastatin was more efficacious,
      was more potent, and demonstrated less interindividual variability than
      simvastatin. A pharmacodynamic variant emerging from randomized trials (PRDM16)
      was associated with Emax for both. For atorvastatin, Emax was 51.7 mg/dl in
      subjects homozygous for the minor allele vs. 75.0 mg/dl for those homozygous for
      the major allele. We also identified several loci associated with ED50. The
      extraction of rigorously defined traits from EMRs for pharmacogenetic studies
      represents a promising approach to further understand the genetic factors
      contributing to drug response. 

PMID- 24096972
TI  - A common error in the ecological regression of cancer incidence on the
      deprivation index.
AB  - OBJECTIVE: To determine if introducing age as another explanatory variable in an
      ecological regression model relating crude rates of cancer incidence and a
      deprivation index provides better results than the usual practice of using the
      standard incidence ratio (SIR) as the response variable, introducing the non
      standardized index, and not including age in the model. METHODS: Relative risks
      associated with the deprivation index for some locations of cancer in Spain's
      Girona Health Region were estimated using two different models. Model 1 estimated
      relative risks with the indirect method, using the SIR as the response variable.
      Model 2 estimated relative risks using age as an explanatory variable and crude
      cancer rates as the response variable. Two scenarios and two sub-scenarios were
      simulated to test the properties of the estimators and the goodness of fit of the
      two models. RESULTS: The results obtained from Model 2's estimates were slightly
      better (less biased) than those from Model 1. The results of the simulation
      showed that in all cases (two scenarios and two sub-scenarios) Model 2 had a
      better fit than Model 1. The probability density for the parameter of interest
      provided evidence that Model 1 leads to biased estimates. CONCLUSIONS: When
      attempting to explain the relative risk of incidence of cancer using ecological
      models that control geographic variability, introducing age as another
      explanatory variable and crude rates as a response variable provides less biased
      results.

PMID- 24096973
TI  - Recruitment of Caribbean female commercial sex workers at high risk of HIV
      infection.
AB  - OBJECTIVE: To evaluate novel eligibility criteria and outreach methods to
      identify and recruit women at high risk of HIV-1 infection in the Caribbean.
      METHODS: A prospective cohort study was conducted in 2009-2012 among 799 female
      commercial sex workers in the Dominican Republic, Haiti, and Puerto Rico. Minimum
      eligibility criteria included exchange of sex for goods, services, or money in
      the previous 6 months and unprotected vaginal or anal sex with a man during the
      same period. Sites used local epidemiology to develop more stringent eligibility
      criteria and recruitment strategies. Participants were asked questions about
      HIV/AIDS and their level of concern about participating in an HIV vaccine trial.
      Logistic regression modeling was used to assess predictors of prevalent HIV
      infection and willingness to participate in a future HIV vaccine study. RESULTS:
      HIV prevalence at screening was 4.6%. Crack cocaine use [odds ratio (OR) = 4.2,
      95% confidence interval (CI) (1.8-9.0)] was associated with and having sex with
      clients in a hotel or motel [OR = 0.5, CI (0.3-1.0)] was inversely associated
      with HIV infection. A total of 88.9% of enrolled women were definitely or
      probably willing to participate in a future HIV vaccine trial. CONCLUSIONS: This
      study indicated that local eligibility criteria and recruitment methods can be
      developed to identify and recruit commercial sex workers with higher HIV
      prevalence than the general population who express willingness to join an HIV
      vaccine trial.

PMID- 24096974
TI  - [Administration of folic acid and other micronutrients to pregnant women in
      Colombia].
AB  - OBJECTIVE: To characterize the intake of folic acid (FA) and other micronutrients
      in medicinal form in a group of pregnant women in Colombia. METHODS: Descriptive
      observational study. Information was obtained from interviews of pregnant women
      and from the clinical records of their prenatal check-ups and/or delivery in four
      cities in Colombia. The sample consisted of 1 637 women seen in 15 institutions.
      RESULTS: A total of 1 315 pregnant women (80.3%) were advised to take FA, and 84%
      received a prescription, 90.3% of whom adhered to the treatment. FA was provided
      to 85.6% of them by their health insurance company and 10.7% purchased it
      themselves. The prescription was appropriate for 0.2% of the women; its use was
      entirely appropriate for 0.2% of the pregnant women and totally inappropriate for
      41.9%. Other micronutrients were recommended to 1 192 women (72.8%), 77.6% of
      whom received the advice from their physician, with 88.7% adhering to the
      treatment. CONCLUSIONS: FA and other micronutrients are inappropriately
      recommended to pregnant women and taken without assessing their individual needs.
      The usefulness of programs that promote mass consumption of micronutrients in
      medicinal form during pregnancy should be reexamined. These programs seem not to
      recognize the fundamental causes of the population's nutritional problems.

PMID- 24096975
TI  - [Determinants of cellular atypia detection in the cervical screening program in
      Rio de Janeiro, Brazil].
AB  - OBJECTIVE: To identify the main determinants of cellular atypia detection in the
      cervical screening program in the state of Rio de Janeiro, Brazil, using data
      from the Cervical Cancer Information System SISCOLO. METHODS: A random sample of
      65 535 Pap smears performed in 2007 was obtained from SISCOLO. This sample was
      used to produce a logistic regression model to identify variables that impact the
      process of detecting cellular atypia. A ROC curve was used to define the most
      suitable cutoff point to classify the presence or absence of atypia. A
      sensitivity analysis was performed to assess the impact on the model of factors
      related to the organization of the service model. RESULTS: The variables of
      impact were "reference laboratory," which reflects laboratory production scale;
      "presence of cellular elements representative of the transformation zone," which
      reflects the quality of the sampling; "immature squamous metaplasia," "presence
      of other benign cellular changes," and "absence of typical vaginal
      microorganisms." Each increase of 1 year in age was associated with a 1.7%
      reduction in the chance of detecting atypia. The ROC curve defined a cutoff of
      4.5%, which allowed the maximization of the model's sensitivity (73.0%) and
      specificity (66.8%). Sensitivity analysis indicated an increase of 46.4% in the
      frequency of atypia following a simulated increase in the number of samples
      analyzed in the excellence (42.9%) and in the presence of cellular elements
      representative of the transformation zone (43.0%). CONCLUSIONS: The model
      revealed that the detection of atypical cells is strongly influenced by
      organizational factors such as adequate sample collection and laboratory size.
      Because these factors can be changed by adequate management practices, the
      proposed model may be an important tool to improve cervical screening programs.

PMID- 24096976
TI  - Diabetes mortality in Panama and related biological and socioeconomic risk
      factors.
AB  - OBJECTIVE: To estimate mortality from diabetes mellitus (DM) for the period 2001
      2011 in the Republic of Panama, by province/indigenous territory, and determine
      its relationship with biological and socioeconomic risk factors. METHODS: Cases
      for the years 2001-2011 with DM listed as the principal cause of death were
      selected from Panama's National Mortality Registry. Crude and adjusted mortality
      rates were generated by sex, age, and geographic area. Linear regression analyses
      were performed to determine the relationship between DM mortality and biological
      and socioeconomic risk factors. A composite health index (CHI) calculated from
      biological and socioeconomic risk factors was estimated for each
      province/indigenous territory in Panama. RESULTS: DM mortality rates did not
      increase for men or women during 2001-2011. Of the biological risk factors, being
      overweight had the strongest association with DM mortality. Of the socioeconomic
      risk factors, earning less than US$ 100 per month had the strongest association
      with DM mortality. The highest socioeconomic CHI scores were found in a province
      that is predominantly rural and in areas with indigenous populations. The highest
      biological CHI scores were found in urban-rural provinces and those with the
      highest percentage of elderly people. CONCLUSIONS: Regional disparities in the
      association between DM mortality and DM risk factors reaffirm the heterogeneous
      composition of the Panamanian population and the uneven distribution of
      biological and social determinant risk factors in the country and point to the
      need to vary management strategies by geographic area for this important cause of
      disability and death in Panama.

PMID- 24096977
TI  - Perceptions regarding oral rehydration solutions for the management of diarrhea
      in Guatemalan children: implications for diarrheal management in the Americas.
AB  - OBJECTIVE: To describe knowledge and perceptions regarding the use of oral
      rehydration solution (ORS) for the management of diarrheal diseases among formal
      and informal health care providers and community caregivers in the Guatemalan
      department of Santa Rosa, and to recommend strategies to increase ORS use for
      management of diarrhea in children. METHODS: From July to September 2008, in
      depth, semi-structured interviews were conducted with formal health care
      providers; open-ended interviews were conducted with informal health care
      providers; and focus group discussions and pile sorting were carried out with
      community caregivers. RESULT: The study participants attributed episodes of
      diarrhea in children to culturally recognized or folk ailments (empacho, cuajo,
      and varillas) that are primarily treated by traditional healers. There were
      knowledge deficits about 1) dehydration as a manifestation of diarrhea, and 2)
      management of dehydration, including the use of ORS and the need to continue
      feedings during diarrheal episodes. Caregivers perceived bottled/ready-made ORS
      products and the more expensive over-the-counter antidiarrheal medications as
      superior to ORS packets in the treatment of diarrhea. CONCLUSIONS: In Guatemala,
      folk etiologies of disease differ from those of the biomedical establishment and
      influence the decisions made by caregivers when treating ill children, including
      those related to the use of ORS. Public health campaigns addressing the treatment
      and management of diarrheal diseases in Santa Rosa should recognize the ailments
      known as empacho, cuajo, and varillas and target them for ORS use by community
      caregivers as well as health care providers in both the formal and informal
      health sectors.

PMID- 24096978
TI  - [Family practices related to breast-feeding maintenance: literature review and
      meta-synthesis].
AB  - OBJECTIVE: To identify and summarize family practices related to the maintenance
      of breast-feeding. METHODS: We conducted a literature review and meta-synthesis
      of the findings of selected articles. Fourteen articles published in English,
      Portuguese, and Spanish between 1989 and 2009 were selected. RESULTS: The
      synthesis revealed five categories concerning family practices related to the
      maintenance of breast-feeding: 1) emotional support, which involves welcoming the
      mother and the baby, valuing and encouraging breast-feeding, and emphasizing the
      value of breast-feeding; 2) instrumental support, which covers attending prenatal
      consultations and home visits, participating in baby care, and providing help in
      everyday tasks beyond the first few weeks postpartum; 3) informational support,
      which involves stating the wish to be involved in breast-feeding and encouraging
      the mother, but not forcing her to share experiences; 4) presence support, which
      involves being close to the mother and taking the time to listen to her; and 5)
      self-support, which involves maintaining positive expectations about breast
      feeding. CONCLUSIONS: The results show that practices defined as support
      contribute to the maintenance of breast-feeding for longer periods. These
      findings underscore the need for expansion of the care provided to women,
      children, and families to include issues related to interpersonal interactions.

PMID- 24096979
TI  - Spatial epidemiology of bat-borne rabies in Colombia.

PMID- 24096980
TI  - [Immigrant generation and diabetes risk among Mexican Americans: the Sacramento
      Area Latino Study on Aging].
AB  - OBJECTIVE: We examined whether acculturation and immigrant generation, a marker
      for assimilation, are associated with diabetes risk in an aging Mexican origin
      population. METHODS: We analyzed data on 1789 adults aged 60 to 101 years from
      the Sacramento Area Latino Study on Aging. We ascertained type 2 diabetes on the
      basis of diabetic medication use, self-report of physician diagnosis, or a
      fasting glucose of 126 milligrams/deciliter or greater. Logistic regression
      modeled prevalent diabetes. RESULTS: Adjusting for age and gender, we observed
      significant but divergent associations between immigrant generation,
      acculturation, and diabetes risk. Relative to first-generation adults, second
      generation adults had an odds ratio (OR) of 1.8 (95% confidence interval [CI] =
      1.4, 2.4) and third-generation adults had an OR of 2.1 (95% CI = 1.4, 3.1) of
      having diabetes. Greater US acculturation, however, was associated with a
      slightly decreased diabetes rate. In the full model adjusting for socioeconomic
      and lifestyle factors, the association between generation (but not acculturation)
      and diabetes remained significant. CONCLUSIONS: Our study lends support to the
      previously contested notion that assimilation is associated with an increased
      diabetes risk in Mexican immigrants. Researchers should examine the presence of a
      causal link between assimilation and health more closely.

PMID- 24096981
TI  - Right ventricular thrombus in a patient with nephrotic syndrome.
AB  - We treated a 21-year-old man with right ventricular thrombus caused by nephrotic
      syndrome. The right ventricular thrombus was safely removed and his postoperative
      course was uneventful. Peri- and postoperative management after surgery for the
      worsened nephrotic syndrome was relatively unique and difficult, and critical
      care was essential for saving the patient's life and protecting renal function. 

PMID- 24096982
TI  - Chest tube insertion is one important factor leading to intercostal nerve
      impairment in thoracic surgery.
AB  - OBJECTIVES: Chest tube insertion seems to be one important factor leading to
      intercostal nerve impairment. The purpose of this prospective study was to
      objectively evaluate intercostal nerve damage using current perception threshold
      testing in association with chest tube insertion. METHODS: Sixteen patients were
      enrolled in this study. Intercostal nerve function was assessed with a series of
      2000-Hz (Abeta fiber), 250-Hz (Adelta fiber), and 5-Hz (C fiber) stimuli using
      current perception threshold testing (Neurometer CPT/C((r))). Current perception
      threshold values at chest tube insertion were measured before surgery, during
      chest tube insertion and after removal of the chest tube. Intensities of ongoing
      pain were also assessed using a numeric rating scale (0-10). RESULTS: Current
      perception thresholds at each frequency after surgery were significantly higher
      than before surgery. Numeric rating scale scores for pain were significantly
      reduced from 3.3 to 1.9 after removal of the chest tube (p = 0.004). The
      correlation between current perception threshold value at 2000 Hz and intensity
      of ongoing pain was marginally significant (p = 0.058). CONCLUSIONS: This is the
      first study to objectively evaluate intercostal nerve damage at chest tube
      insertion. The results confirmed that chest tube insertion has clearly
      deleterious effects on intercostal nerve function.

PMID- 24096984
TI  - Anisotropic surface strain in single crystalline cobalt nanowires and its impact
      on the diameter-dependent Young's modulus.
AB  - Understanding and measuring the size-dependent surface strain of nanowires are
      essential to their applications in various emerging devices. Here, we report on
      the diameter-dependent surface strain and Young's modulus of single-crystalline
      Co nanowires investigated by in situ X-ray diffraction measurements. Diameter
      dependent initial longitudinal elongation of the nanowires is observed and
      ascribed to the anisotropic surface stress due to the Poisson effect, which
      serves as the basis for mechanical measurements. As the nanowire diameter
      decreases, a transition from the "smaller is softer" regime to the "smaller is
      tougher" regime is observed in the Young's modulus of the nanowires, which is
      attributed to the competition between the elongation softening and the surface
      stiffening effects. Our work demonstrates a new nondestructive method capable of
      measuring the initial surface strain and estimating the Young's modulus of single
      crystalline nanowires, and provides new insights on the size effect. 

PMID- 24096983
TI  - Occlusion of portosystemic shunts improves hyperinsulinemia due to insulin
      resistance in cirrhotic patients with portal hypertension.
AB  - BACKGROUND: Liver cirrhosis (LC) is often complicated by hyperinsulinemia due to
      insulin resistance (IR), which is considered to be closely related to shunt
      formation and impaired liver function. This study evaluates whether balloon
      occluded retrograde transvenous obliteration (B-RTO) can affect glucose and
      insulin metabolism in patients with LC. METHODS: Twenty-five cirrhotic patients
      (mean age = 69.6 years; female/male = 12/13; hepatitis C
      virus/alcohol/nonalcoholic steatohepatitis = 14/6/5; Child-Pugh's class A/B =
      10/15) with gastric varices and/or hepatic encephalopathy caused by portosystemic
      shunts (PSS) due to portal hypertension (PH) underwent B-RTO at our hospital.
      Testing was performed before and at 1 month after the procedure. RESULTS: Shunt
      occlusion resulted in a decrease in extrahepatic collateral blood flow and an
      increase in portal venous flow, as well as a dramatic improvement in hepatic
      function markers. In addition, B-RTO significantly decreased homeostasis model
      assessment (HOMA) of IR without a statistical decline of HOMA of beta-cell
      function. The 75-g oral glucose tolerance test (75-OGTT) revealed that occlusion
      of PSS reduced both fasting immunoreactive insulin (IRI) levels and the area
      under the curve for IRI. However, no significant change in preprandial or
      postprandial plasma glucose levels was observed. Furthermore, according to the
      criteria of the American Diabetes Association, B-RTO led to an improved 75-OGTT
      profile in 58.3 % of patients who had impaired glucose tolerance or diabetes
      mellitus before the procedure. CONCLUSIONS: Shunt occlusion improves IR-related
      hyperinsulinemia through increased portal venous flow, ameliorated liver
      function, and consequent augmented hepatic insulin clearance in cirrhotic
      patients with PH.

PMID- 24096985
TI  - Tip-enhanced nano-Raman analytical imaging of locally induced strain distribution
      in carbon nanotubes.
AB  - Tip-enhanced Raman scattering microscopy is a powerful technique for analysing
      nanomaterials at high spatial resolution far beyond the diffraction limit of
      light. However, imaging of intrinsic properties of materials such as individual
      molecules or local structures has not yet been achieved even with a tip-enhanced
      Raman scattering microscope. Here we demonstrate colour-coded tip-enhanced Raman
      scattering imaging of strain distribution along the length of a carbon nanotube.
      The strain is induced by dragging the nanotube with an atomic force microscope
      tip. A silver-coated nanotip is employed to enhance and detect Raman scattering
      from specific locations of the nanotube directly under the tip apex, representing
      deformation of its molecular alignment because of the existence of local strain.
      Our technique remarkably provides an insight into localized variations of
      structural properties in nanomaterials, which could prove useful for a variety of
      applications of carbon nanotubes and other nanomaterials as functional devices
      and materials. 

PMID- 24096988
TI  - Temperature-dependent appearance of forensically useful flies on carcasses.
AB  - Flies are frequently used for postmortem interval (PMI) estimations. These
      estimates are usually based on the age of larval or pupal specimens. However, the
      age defines only the minimum PMI. In order to move forensic entomology further, a
      method useful for the estimation of an interval preceding insect appearance on a
      corpse called the pre-appearance interval (PAI) is needed. Recently, it was
      demonstrated that the PAI of several carrion beetles is closely related to the
      temperature prevailing throughout this interval. Hence, it was postulated to
      estimate PAI from temperature. In order to check premises for using this approach
      with flies, a test of the relationship between adult or oviposition PAI and
      temperature was made for nine species of European flies. Data on PAI originated
      from pig carcasses decomposing under various temperatures. Adult PAI of Hydrotaea
      dentipes, Hydrotaea ignava, Hydrotaea similis, Phormia regina, and Stearibia
      nigriceps and oviposition PAI of S. nigriceps were exponentially related to
      temperature. Only S. nigriceps revealed a close relationship, demonstrating solid
      premises for PAI estimation from temperature alone. Adult and oviposition PAI of
      Calliphora vomitoria and adult PAI of Hydrotaea pilipes were not related to
      temperature. Adult and oviposition PAI of Lucilia sericata and Lucilia caesar
      responded similarly, with an abrupt and large increase in a narrow range of low
      temperatures and no response in a broad range of high temperatures. Probably,
      different mechanisms form the basis for the response of PAI to temperature in
      flies colonizing carcasses shortly after death and flies colonizing carcasses
      later in the decomposition process. 

PMID- 24096986
TI  - Revisiting the evidence on health and health care disparities among the Roma: a
      systematic review 2003-2012.
AB  - OBJECTIVES: To conduct a systematic review of the epidemiological and health
      service utilization literature related to the Roma population between 2003 and
      2012. METHODS: Systematic review of empirical research related to Roma health and
      health care utilization published between 2003 and 2012 identified through
      electronic databases (PsycInfo, Medline, Google Scholar). Methodological rigor
      was evaluated using a six-point set of design criteria. RESULTS: We found
      evidence for lower self-reported health and significantly higher mortality risk
      for Roma compared to non-Roma, and greater prevalence of health risk factors for
      Roma children, including environmental risks, low birth weight, and lower
      vaccination coverage. Studies of non-communicable and infectious disease remain
      insufficient to make firm conclusions on disparities. Barriers to care include
      lack of documentation and affordability of care, though more studies on health
      care utilization are needed. CONCLUSIONS: Roma youth and adults are in need of
      programs that reduce health disparities and their increased mortality risk.
      Reducing exposure to risk factors such as smoking, obesity, and poor living
      conditions may be a target for interventions. More intervention studies and
      rigorous evaluations are needed.

PMID- 24096987
TI  - Mechanism of amyloid beta-protein dimerization determined using single-molecule
      AFM force spectroscopy.
AB  - Abeta42 and Abeta40 are the two primary alloforms of human amyloid beta-protein
      (Abeta). The two additional C-terminal residues of Abeta42 result in elevated
      neurotoxicity compared with Abeta40, but the molecular mechanism underlying this
      effect remains unclear. Here, we used single-molecule force microscopy to
      characterize interpeptide interactions for Abeta42 and Abeta40 and corresponding
      mutants. We discovered a dramatic difference in the interaction patterns of
      Abeta42 and Abeta40 monomers within dimers. Although the sequence difference
      between the two peptides is at the C-termini, the N-terminal segment plays a key
      role in the peptide interaction in the dimers. This is an unexpected finding as N
      terminal was considered as disordered segment with no effect on the Abeta peptide
      aggregation. These novel properties of Abeta proteins suggests that the
      stabilization of N-terminal interactions is a switch in redirecting of amyloids
      form the neurotoxic aggregation pathway, opening a novel avenue for the disease
      preventions and treatments. 

PMID- 24096989
TI  - Detection of acquired hemoglobinopathy in children with hematological
      malignancies at disease onset: results form a national referral centre.
AB  - Abnormal hemoglobin synthesis is usually inherited but may also arise as a
      secondary manifestation of a hematological neoplasia. The objective of this study
      is to identify the presence of acquired hemoglobinopathy in children diagnosed
      with hematological malignancies and compare these against healthy controls.
      Prospective matched case-control study held from 2010 to 2012. For each patient
      with hematological malignancy two healthy controls matched on gender, age and
      race were recruited. Patients with other co-morbidities were excluded. All
      samples underwent supravital staining and high-performance liquid chromatography
      (HPLC) electrophoresis. Following identification of abnormal results, molecular
      genetic testing for all alpha- and beta-thalassemia mutations prevalent in the
      Greek population was performed. Other causes of anemia were ruled out based on
      specific testing. A total of 44 (32 males) patients with a mean age of 7.1 years
      were enrolled in the study. Hematological disorders included acute lymphocytic
      leukemia (24), acute myeloid leukemia (8), non-Hodgkin lymphoma (8), Hodgkin
      disease (3), and Langerhans cell histiocytosis (1). Following exclusion of
      congenital hemoglobinopathies, atypical HPLC electrophoretic findings persisted
      in 18.1 % of the patient group, compared to 0 % in the control group (p < 0.001).
      The patient group showed marked microcytic anemia (p < 0.01) and detection of
      small inclusions (p = 0.034) on supravital staining. Comparison of the HPLC
      findings between the groups demonstrated significantly lower percentages of HbA
      (p = 0.02), normal HbA2 and higher percentage of fast moving Hb bands (p = 0.04)
      in the patient group. Interestingly, the majority of these patients belonged to
      the high-risk group. Acquired hemoglobinopathy is recognized in adult patients.
      This is a novel study describing evidence of abnormal erythropoiesis in children
      with hematological malignancies and in particular those classified as high-risk
      cancer patients according to international criteria.

PMID- 24096990
TI  - Size tunable fluorescent nano-graphite oxides: preparation and cell imaging
      applications.
AB  - Fluorescent nano-graphite oxides (NGO) with different size distribution were
      prepared via a one-pot hydrothermal route using ultrasmall graphite powder as
      starting material and subsequently separated using dialysis tubes with different
      molecular weight cutoff. The biomedical applications of these NGO for cell
      imaging were further investigated. Fourier transform infrared spectra
      demonstrated that many functional groups including the hydroxyl group, carboxyl
      group and epoxy group were present on NGO, which endowed them with good water
      solubility. These NGO showed size-dependent photoluminescence and excellent
      biocompatibility with A549 cells. As evidenced by laser scanning confocal
      microscopy images, NGO could be internalized by A549 cells and located in the
      cytoplasm. Given their good water solubility, size tunable photoluminescence and
      excellent biocompatibility, these NGO should be promising for bioimaging and
      various biomedical applications. 

PMID- 24096991
TI  - Influence of guest loading on thermal properties of NaxSi136 clathrates.
AB  - Thermal properties of a series of type II clathrates of the formula NaxSi136 with
      0 < x < 24 and Na guests occupying the Si cages have been investigated over the
      temperature range from 2 to 300 K. Heat capacity and thermal conductivity results
      show that the structure is remarkably responsive to the loading of Na guests. The
      response is phononic: the host lattice expands in a non-monotonic way, and first
      stiffens, then relaxes at low loading into the larger Si28 cages (x < 9), then
      stiffens again as the Na concentration increases further. The response is also
      electronic, through changes in electronic properties as additional Na is loaded
      into the smaller Si20 cages at high loading (x > 9). In total, the influence of
      the guest loading illustrates the complexities of structure-property relations in
      a guest-host system.

PMID- 24096992
TI  - Report about the 35th Annual Meeting of the Cognitive Science Society.

PMID- 24096993
TI  - The influence of intentional versus incidental retrieval practices on the role of
      recollection in test-enhanced learning.
AB  - A testing effect occurs when taking a test leads to more durable memory for
      tested materials, relative to restudying them during the same period of time. In
      the current study, we examined whether incidental and intentional restudy/testing
      practice modes during a practice phase would modulate the contribution of
      recollection-based and familiarity-based retrieval in a final recognition test.
      Both practice strategy (restudy versus testing) and practice mode (incidental vs.
      intentional) were manipulated between participants (N = 160). The restudy and
      testing groups performed a semantic rating task and a word fragment completion
      task, respectively, in the incidental condition or in the intentional condition.
      Only those participants in the intentional condition were instructed to recall or
      restudy the targets. All participants went through two study-practice cycles that
      involved two different sets of targets. After the second cycle, participants
      performed a list-discrimination recognition test that could assess the
      contributions of recollection-based and familiarity-based retrieval on test
      enhanced learning. The testing effect occurred in the intentional condition, but
      not in the incidental condition. Relative to intentional restudy, intentional
      testing boosted recollection, but not familiarity, demonstrating the role of
      recollection in test-enhanced learning. 

PMID- 24096994
TI  - GH secretion reserve in subclinical hypercortisolism.
AB  - PURPOSE: In overt hypercortisolism, growth hormone (GH) secretion is decreased
      and normalizes after surgery. In subclinical hypercortisolism (SH), GH secretion
      has been scarcely investigated. We assessed GH reserve in patients with and
      without SH and, in the former, also after recovery. METHODS: We enrolled 24
      patients with adrenal adenomas, 12 with SH (SH+, 8 females, 58.3 +/- 6.5 years)
      and 12 without SH (SH-; 11 females, 61.8 +/- 10.6 years). SH was diagnosed in the
      presence of >= 2 out of: 1 mg overnight dexamethasone suppression test >83
      nmol/L, urinary free cortisol (UFC) >193 nmol/day and ACTH levels <2.2 pmol/L. GH
      secretion was assessed by GHRH + Arginine test (GHRH-ARG) and age-adjusted serum
      IGF-I levels, expressed as SDS (IGF-I SDS). Eight SH+ patients were re-evaluated
      after the recovery from SH. RESULTS: Age, gender, body mass index (BMI) and IGF-I
      SDS were comparable between SH+ and SH- patients. After GHRH-ARG the mean GH peak
      levels (GH-P) and GH response (as Area Under Curve, GH-AUC) were lower in SH+
      than in SH- patients (15.2 +/- 8.1 vs 44.5 +/- 30.9 MUg/L, P = 0.004 and 1,418 +/
      803 vs 4,028 +/- 2,476 MUg/L/120 min, P = 0.002, respectively), after adjusting
      for age and BMI. The GH-AUC and GH-P levels were negatively associated with UFC
      after adjusting for age and BMI (beta = -0.39, P = 0.02 and beta = -0.4, P =
      0.020 respectively). After recovery, GH-P levels and GH-AUC increased as compared
      to baseline (23.7 +/- 16.3 vs 15.8 +/- 10.2 MUg/L, P = 0.036 and 2,549 +/- 1,982
      vs 1,618 +/- 911 MUg/L/120 min, P = 0.012, respectively). CONCLUSIONS: GH
      secretion reserve is decreased in SH patients and increases after the recovery.

PMID- 24096995
TI  - A semi-automated region of interest detection method in the scintigraphic
      glomerular filtration rate determination for patients with abnormal low renal
      function.
AB  - PURPOSE: This work presents a novel semi-automated renal region-of-interest (ROI)
      determination method that is user friendly, time saving, and yet provides a
      robust glomerular filtration rate (GFR) estimation highly consistent with the
      reference method. SUBJECTS AND METHODS: We reviewed data from 57 patients who
      underwent (99m)Tc-diethylenetriaminepentaacetic acid renal scintigraphy and were
      diagnosed with abnormal renal function. The renal and background ROIs were
      delineated by the proposed multi-step, semi-automated method, which integrates
      temporal/morphologic information via visual inspection and computer-aided
      calculations. The total GFR was estimated using the proposed method (sGFR)
      performed by 2 junior clinicians (A and B) with 1 and 3 years of experience,
      respectively (sGFR_a, sGFR_b), and compared with the reference total GFR (rGFR)
      estimated by a senior clinician with 20 years of experience who manually
      delineated the kidney and background ROIs. All GFR calculations herein were
      conducted using the Gates method. RESULTS: Data from 10 patients with unilateral
      or non-functioning kidneys were excluded from the analysis. For the remaining
      patients, sGFR correlated well with rGFR (r(s/rGFR_a) = 0.957, P < 0.001 and
      r(s/rGFR_b) = 0.951, P < 0.001) and sGFR_a correlated well with sGFR_b (r(a/b) =
      0.997, P < 0.001). Moreover, the Bland-Altman plots for sGFR_a and sGFR_b confirm
      the high reproducibility of the proposed method between different operators.
      Finally, the proposed procedure is almost 3 times faster than the routinely used
      procedure in clinical practice. CONCLUSION: The results suggest that this method
      is easy to use, highly reproducible, and accurate in measuring the GFR of
      patients with low renal function. The method is being further extended to a fully
      automated procedure.

PMID- 24096996
TI  - Solitary breast metastasis from recurrent gallbladder carcinoma simulating a
      second primary on 18F-FDG PET/CT.
AB  - Gallbladder carcinoma is characterized by poor prognosis. It spreads by direct,
      lymphatic, vascular, neural, intraperitoneal, and intraductal routes. The most
      commonly involved organ is the liver followed by regional lymph nodes. Extra
      abdominal metastases are comparatively rare. We present a case of solitary breast
      metastasis from recurrent gallbladder carcinoma mimicking a primary breast cancer
      in (18)F-FDG PET/CT.

PMID- 24096997
TI  - Glucose transporter 3 and 1 may facilitate high uptake of 18F-FDG in gastric
      schwannoma.
AB  - Recently, some gastric schwannomas have been reported to have high uptake of FDG.
      However, Glut-1 was reported to be negative in gastric schwannomas tested. A 64
      year-old female patient received a laparoscopic partial gastrectomy for a FDG PET
      positive submucosal tumor (SUVmax 6.61). The resected tumor was diagnosed as a
      benign gastric schwannoma. Glut family immunohistochemical examination revealed
      diffuse positive expression of Glut-3 and partial positive expression of Glut-1.
      On the other hand, Glut-2 and Glut-4 expression in the tumor were negative. This
      case suggested that Glut-3 and Glut-1 expression were facilitators of high FDG
      uptake in the benign gastric schwannoma. 

PMID- 24096998
TI  - Incidental finding of anterior cranial fossa meningioma on 18F-fluoride PET/CT.
AB  - The association of breast carcinoma and meningioma has been described. We report
      a case of anterior cranial fossa meningioma in a woman with breast cancer
      detected by (18)F-fluoride PET/CT. The whole-body (18)F-fluoride PET images
      demonstrate an intense intracranial focal radiotracer accumulation in the skull
      base. Simultaneous CT showed a corresponding calcified space-occupying lesion
      consistent with meningioma. Follow-up CT image obtained 8 months later
      demonstrated the persistence and stable appearance of the lesion.

PMID- 24096999
TI  - Comparison of whole-body versus limited whole-body 18F-FDG PET/CT scan in
      malignant cutaneous melanoma.
AB  - OBJECTIVES: The objectives of this study were to estimate retrospectively the
      incidence of clinically significant findings in the lower extremities in patients
      with malignant cutaneous melanoma scanned from the skull vertex to the bottom of
      the feet and whether these add additional diagnostic and prognostic information
      and to demonstrate a confidence interval that would support exclusion of lower
      extremity scans in these patients. METHODS: This is a retrospective study of 200
      patients who underwent (18)F-FDG PET/CT for staging melanoma. Whole-body PET/CT
      scans including the lower extremities were reviewed. PET/CT findings in the lower
      extremities were tabulated by location, pathology, and clinical progress notes
      with documented clinical history and physical examination correlation. RESULTS:
      Among the 200 PET/CT scans, 3 scans had positive findings in the lower
      extremities. A biopsy was performed on 1 lesion, which was found to be an
      incidental squamous cell carcinoma. One lesion was considered a benign finding
      from inflammation demonstrated by clinical follow-up. One scan had a metastasis
      to the proximal femur, which is included in the standard FOV (eyes to midthighs).
      In this case series, the lower extremities' true-positive findings never impacted
      or changed clinical management. CONCLUSIONS: Our study confirms with a high
      degree of confidence that in patients with malignant cutaneous melanoma,
      additional lower-extremity scan results in little additional useful information
      and could be discontinued in patients whose melanoma did not arise in the lower
      extremities. PET/CT acquisition of the lower extremities results in increased
      scan time and unnecessary extra radiation dose from CT to melanoma patients.

PMID- 24097000
TI  - Findings of 123I-iomazenil SPECT during and after stroke-like episodes in a
      patient with MELAS.
AB  - Reduced cortical benzodiazepine receptor binding potential in late images of I
      iomazenil SPECT indicates neuronal damage in the cortex. We present the case of a
      31-year-old woman with mitochondrial myopathy, encephalopathy, lactic acidosis,
      and stroke-like episodes (MELAS) who had focal seizures in the right hand. FLAIR
      imaging in the ictal state revealed a high-intensity lesion in the left post
      central gyrus, while I-iomazenil SPECT showed decreased tracer uptake in this
      lesion. The lesion completely disappeared on FLAIR imaging performed 1 month
      after the focal seizures; in contrast, I-iomazenil SPECT still revealed a
      significant decrease in tracer uptake in this lesion. 

PMID- 24097001
TI  - Synchronous ileocecal neuroendocrine tumor and carotid chemodectoma: diagnosis by
      111In pentetreotide SPECT/CT.
AB  - We report a case of carotid chemodectoma diagnosed by In pentetreotide SPECT/CT.
      A 72-year-old woman with an ileocecal neuroendocrine tumor underwent whole-body
      In pentetreotide scintigraphy for exclusion of distant metastases. Planar
      scintigraphy demonstrated marked tracer uptake in the ileocecal region and
      intense focal tracer accumulation within the neck. SPECT/CT demonstrated a space
      occupying lesion at the carotid bifurcation. Histopathological evaluation
      revealed carotid chemodectoma. SPECT/CT is a valuable tool for the evaluation and
      precise anatomical localization of tracer uptake. In addition, other benign or
      malignant pathologies accumulating In pentetreotide may mimic neuroendocrine
      tumor metastases and should be considered particularly in unusual localizations. 

PMID- 24097002
TI  - A case of colon cancer incidentally detected by 18F-choline PET/CT.
AB  - A 65-year-old man had restaging of prostate cancer with an 18F-choline PET/CT,
      which revealed focal uptake in a thickened posterior wall of sigmoid colon.
      Biopsy demonstrated colon cancer. Incidental colorectal 18F-choline uptake should
      be further investigated with histological analysis.

PMID- 24097003
TI  - Iris metastasis in a patient with small cell lung cancer: incidental detection
      with 18F-FDG PET/CT.
AB  - Iris metastasis is one of the rare forms of ocular metastasis. Lung and breast
      cancers represent more than two thirds of the primary tumor sites in such
      patients. We here present the F-FDG PET/CT findings in a 60-year-old male patient
      with small cell lung cancer where metastasis to iris was incidentally discovered
      on PET/CT. 

PMID- 24097004
TI  - Pulmonary amyloidosis in a patient with Langerhans cell histiocytosis: diagnostic
      dilemma on 18F-FDG PET/CT.
AB  - Amyloidosis associated with Langerhans cell histiocytosis (LCH) is extremely
      rare. We here present the 18F-FDG PET/CT images of a 48-year-old male patient
      with multifocal skeletal involvement of LCH. In addition, he had a left lung
      upper lobe 18F-FDG avid mass that was misinterpreted as pulmonary involvement of
      LCH on PET/CT. Biopsy from the mass showed amyloidosis. Therefore, amyloidosis
      should be kept as a differential for 18F-FDG pulmonary avid nodule.

PMID- 24097005
TI  - Large thigh and buttock muscle metastases as the initial manifestation of
      follicular thyroid cancer.
AB  - Follicular thyroid carcinoma (FTC) is the second most common thyroid malignancy
      after papillary thyroid carcinoma (PTC). It has a greater tendency than PTC to
      metastasize to distant organs such as the lung and bone. FTC metastasis to
      skeletal muscle is extremely rare. Here, we report a 65-year-old woman with large
      thigh and buttock muscle metastases as the first manifestation of FTC. 

PMID- 24097006
TI  - Lymphoscintigraphy in oral squamous cell carcinoma sentinel node biopsy and its
      role in the surgical planning.
AB  - AIM: The purpose of this study was to analyze the influence of different
      lymphatic pathways on surgical planning and the reliability of sentinel lymph
      node (SLN) biopsy to predict regional recurrence in patients with clinically N0
      oral squamous cell carcinoma (OSCC). METHODS: Twenty-five patients with cT1/T2 N0
      OSCC underwent a lymphoscintigraphy and an SLN biopsy. Elective neck dissection
      was performed at the validation stage and in patients with metastatic SLN.
      Scintigraphic and surgical SLN detection, pathologic status of SLN and of
      elective neck dissection, and regional recurrence in patients with negative SLN
      (pN0(sn)) were all analyzed. RESULTS: Scintigraphic and surgical detection were
      96% and 100%, respectively, with 68% of negative SLN. Lymphoscintigraphy modified
      surgery in 32% of patients. In pN0(sn) patients, the free-of-disease survival
      rate was 88%. CONCLUSIONS: These results support the reliability of sentinel node
      biopsy in OSCC. Presurgical lymphoscintigraphy is essential, because it can
      modify the surgical procedure.

PMID- 24097007
TI  - 68Ga-dotatate avid medullary thyroid cancer with occult liver metastases.
AB  - A 50-year-old male patient with a history of medullary thyroid cancer and
      extensive previous investigation including FDG PET 18 months earlier presented
      for a Ga-dotatate scan. A single area of abnormal uptake was identified in the
      right ninth rib. An MRI scan and bone scan confirmed the bony metastasis;
      however, the MRI of the liver demonstrated multiple liver metastases not apparent
      on the PET study. These remained occult despite coregistration of the MRI and PET
      data. The occult nature of these lesions may have been due to a similar degree of
      uptake in the liver and metastases. 

PMID- 24097008
TI  - Usefulness of 64Cu-ATSM in head and neck cancer: a preliminary prospective study.
AB  - AIMS: Cu-diacetyl-bis(N4-methylthiosemicarbazone) (Cu-ATSM) is a hypoxia-avid,
      positron emitter radiotracer. The primary aim of this study is to assess the
      efficacy of pretherapy Cu-ATSM PET/CT as a prognostic factor of response to
      therapy. The secondary aims are to investigate if there is a difference between
      early and late PET/CT scans and if there is a difference between the biologic
      tumor volume (BTV) in radiotherapy treatment planning calculated between Cu-ATSM
      and F-FDG, and to assess if Cu-ATSM is a prognostic marker of disease
      progression. METHODS: Eleven patients with head and neck cancer treated with
      chemoradiotherapy were enrolled prospectively; both Cu-ATSM and F-FDG PET/CT
      scans before and after treatment were obtained. The Cu-ATSM scans were performed
      after 1 hour (early) and 16 hours (late). RESULTS: All patients had stage III or
      IV squamous cell head and neck cancer; 7 of 11 patients had nodal metastasis, and
      22 cancer foci were detected with Cu-ATSM. SUVmax was 16.2 +/- 7.9, and there was
      no significant SUVmax difference between early and late imaging. F-FDG SUVmax
      before therapy was 15.6 +/- 9.4, whereas F-FDG SUVmax after therapy was 1.5 +/-
      1.2. Sensitivity and specificity values of Cu-ATSM calculated with receiver
      operating characteristic curves were 100% and 50% considering the SUVmax and 100%
      and 33% considering the volume, respectively. No difference has been found
      between the BTV contoured with Cu-ATSM and F-FDG. CONCLUSIONS: The Cu-ATSM scans
      showed high sensitivity but low specificity in predicting neoadjuvant
      chemoradiotherapy response. No difference was noted between early and late scans.
      F-FDG and Cu-ATSM provided similar results about delineation of BTV.

PMID- 24097009
TI  - Splenule disguised as pancreatic mass: elucidated with SPECT liver-spleen
      scintigraphy.
AB  - Splenules are congenital foci of healthy splenic tissue that are separate from
      the main body but are structurally identical to the spleen, derived from
      mesenchymal buds on the left side of the mesogastrium and commonly seen in or
      near the tail of the pancreas. We report a case of a 58-year-old male who was
      found to have a pancreatic tail mass on contrast-enhanced abdominal CT, which was
      similarly disguised as a pancreatic tail mass on both magnetic resonance
      cholangiopancreatography and abdominal MRI. A liver spleen scintigraph with Tc
      sulfur colloid later proved the mass to be a splenule. 

PMID- 24097010
TI  - The secretion of organic acids is also regulated by factors other than aluminum.
AB  - As a result of natural processes and human activities, aluminum (Al) toxicity is
      recognized as a major limiting factor for plant productivity, and the secretion
      of organic acids facilitated by channel proteins is one of the most important Al
      resistance mechanisms in plants. The objective of this study was to evaluate the
      effects of several types of stress, including herbicide (imazethapyr (IM) and
      diclofop-methyl (DM)), heavy metal (Al and Cu), salt stress (NaCl), and proton
      stress (HCl), on the release of organic acids in rice. The results showed that
      0.05 mg/L IM, 0.1 mg/L DM, 4680 mg/L NaCl, 0.5 mg/L CuSO4, and 18 mg/L AlCl3
      significantly inhibited rice root elongation and the root fresh weight. In
      contrast, no significant inhibitory effects on rice growth were found with HCl
      (pH = 4.5). Similar to the effect of AlCl3 on organic acid induction, treatment
      with IM, DM, NaCl, and CuSO4 also induced the synthesis of endogenous citric acid
      and oxalic acid but decreased endogenous malic acid synthesis in the seedlings,
      though only citric acid was released into the environment after these treatments.
      We also analyzed the transcripts of three citrate channel proteins and found they
      were up-regulated by NaCl, CuSO4, and AlCl3 but not by IM or DM. This study
      clarified that organic acid secretion in plants might be a common phenomenon when
      plants are exposed to environmental stress other than Al toxicity. 

PMID- 24097011
TI  - Antibiotic-resistant E. coli in surface water and groundwater in dairy operations
      in Northern California.
AB  - Generic Escherichia coli was isolated from surface water and groundwater samples
      from two dairies in Northern California and tested for susceptibility to
      antibiotics. Surface samples were collected from flush water, lagoon water, and
      manure solids, and groundwater samples were collected from monitoring wells.
      Although E. coli was ubiquitous in surface samples with concentrations ranging
      from several hundred thousand to over a million colony-forming units per 100 mL
      of surface water or per gram of surface solids, groundwater under the influence
      of these high surface microbial loadings had substantially fewer bacteria (3- to
      7-log10 reduction). Among 80 isolates of E. coli tested, 34 (42.5%) were
      resistant to one or more antibiotics and 22 (27.5%) were multi-antibiotic
      resistant (resistant to >=3 antibiotics), with resistance to tetracycline,
      cefoxitin, amoxicillin/clavulanic acid, and ampicillin being the most common. E.
      coli isolates from the calf hutch area exhibited the highest levels of multi
      antibiotic resistance, much higher than isolates in surface soil solids from
      heifer and cow pens, flush alleys, manure storage lagoons, and irrigated fields.
      Among E. coli isolates from four groundwater samples, only one sample exhibited
      resistance to ceftriaxone, chloramphenicol, and tetracycline, indicating the
      potential of groundwater contamination with antibiotic-resistant bacteria from
      dairy operations.

PMID- 24097012
TI  - Seasonal characteristics of SO2, NO2, and CO emissions in and around the Indo
      Gangetic Plain.
AB  - Anthropogenic emissions of sulfur dioxide (SO2), nitrogen dioxide (NO2), and
      carbon monoxide (CO) exert significant influence on local and regional
      atmospheric chemistry. Temporal and spatial variability of these gases are
      investigated using surface measurements by the Central Pollution Control Board
      (India) during 2005-2009 over six urban locations in and around the Indo-Gangetic
      Plain (IGP) and supported using the satellite measurements of these gases. The
      stations chosen are Jodhpur (west of IGP), Delhi (central IGP), Kolkata and
      Durgapur (eastern IGP), Guwahati (east of IGP), and Nagpur (south of IGP). Among
      the stations studied, SO2 concentrations are found to be the highest over Kolkata
      megacity. Elevated levels of NO2 occur over the IGP stations of Durgapur,
      Kolkata, and Delhi. Columnar NO2 values are also found to be elevated over these
      regions during winter due to high surface concentrations while columnar SO2
      values show a monsoon maximum. Elevated columnar CO over Guwahati during pre
      monsoon are attributed to biomass burning. Statistically significant correlations
      between columnar NO2 and surface NO2 obtained for Delhi, Kolkata, and Durgapur
      along with very low SO2 to NO2 ratios (<=0.2) indicate fossil fuel combustion
      from mobile sources as major contributors to the ambient air over these regions.

PMID- 24097013
TI  - Quantitation of metformin in human plasma and urine by hydrophilic interaction
      liquid chromatography and application to a pharmacokinetic study.
AB  - We describe an analytical method for the quantification of the widely used
      antihyperglycemic agent, metformin, in human plasma and urine. The separation was
      performed using isocratic hydrophilic interaction liquid chromatography on a Luna
      hydrophilic interaction liquid chromatography column (125 * 4.6 mm, 3 MUm). The
      sample preparation was accomplished by solid-phase extraction. Validation of the
      method was performed in the range 10-2000 ng/mL for plasma and 5-30 mcg/mL for
      urine. The methods were linear within the investigated range (r(2) > 0.988).
      Within-day repeatability ranged from 3.1% to 7.5% in plasma and 1.6% to 6.2% in
      urine. Between-day reproducibility ranged from 2.9% to 5.3% in plasma and 0.6% to
      1.8% in urine. The inaccuracy expressed as bias ranged from -3.1% to 1.9% in
      plasma and from -7.2% to 0.7% in urine. The lower limit of quantification for
      metformin in plasma was 5 ng/mL and in urine was 40 ng/mL. The method was
      therefore considered to be precise, accurate, reproducible, and sensitive enough
      to be appropriate for pharmacokinetic studies of metformin. The applicability of
      the method for human pharmacokinetic studies was demonstrated by dosing a healthy
      male volunteer with 500-mg metformin hydrochloride as a single oral dose; plasma
      and urine concentrations were measured for 24 hours.

PMID- 24097014
TI  - Alteration of the exopolysaccharide production and the transcriptional profile of
      free-living Frankia strain CcI3 under nitrogen-fixing conditions.
AB  - We investigated the effect of different nitrogen (N) sources on exopolysaccharide
      (EPS) production and composition by Frankia strain CcI3, a N2-fixing actinomycete
      that forms root nodules with Casuarina species. Frankia cells grown in the
      absence of NH4Cl (i.e., under N2-fixing conditions) produced 1.7-fold more EPS,
      with lower galactose (45.1 vs. 54.7 mol%) and higher mannose (17.3 vs. 9.7 mol%)
      contents than those grown in the presence of NH4Cl as a combined N-source. In the
      absence of the combined N-source, terminally linked and branched residue contents
      were nearly twice as high with 32.8 vs. 15.1 mol% and 15.1 vs. 8.7 mol%,
      respectively, than in its presence, while the content of linearly linked residues
      was lower with 52.1 mol% compared to 76.2 mol%. To find out clues for the altered
      EPS production at the transcriptional level, we performed whole-gene expression
      profiling using quantitative reverse transcription PCR and microarray technology.
      The transcription profiles of Frankia strain CcI3 grown in the absence of NH4Cl
      revealed up to 2 orders of magnitude higher transcription of nitrogen fixation
      related genes compared to those of CcI3 cells grown in the presence of NH4Cl.
      Unexpectedly, microarray data did not provide evidence for transcriptional
      regulation as a mechanism for differences in EPS production. These findings
      indicate effects of nitrogen fixation on the production and composition of EPS in
      Frankia strain CcI3 and suggest posttranscriptional regulation of enhanced EPS
      production in the absence of the combined N-source.

PMID- 24097015
TI  - Sensory memory of illusory depth in structure-from-motion.
AB  - When multistable displays (stimuli consistent with two or more equally plausible
      perceptual interpretations) are presented intermittently, their perceptions are
      stabilized by sensory memory. Independent memory traces are generated not only
      for different types of multistable displays (Maier, Wilke, Logothetis, & Leopold,
      Current Biology 13:1076-1085, 2003), but also for different ambiguous features of
      binocular rivalry (Pearson & Clifford, Journal of Vision 4:196-202, 2004). In the
      present study, we examined whether a similar independence of sensory memories is
      observed in structure-from-motion (SFM), a multistable display with two ambiguous
      properties. In SFM, a 2-D planar motion creates a vivid impression of a rotating
      3-D volume. Both the illusory rotation and illusory depth (i.e., how close parts
      of an object appear to the observer) of an SFM object are ambiguous. We
      dissociated the sensory memories of these two ambiguous properties by using an
      intermittent presentation in combination with a forced-ambiguous-switch paradigm
      (Pastukhov, Vonau, & Braun, PLoS ONE 7:e37734, 2012). We demonstrated that the
      illusory depth of SFM generates a sensory memory trace that is independent from
      that of illusory rotation. Despite this independence, the specificities levels of
      the sensory memories were identical for illusory depth and illusory rotation. The
      history effect was weakened by a change in the volumetric property of a shape
      (whether it was a hollow band or a filled drum volume), but not by changes in
      color or size. We discuss how these new results constrain models of sensory
      memory and SFM processing. 

PMID- 24097016
TI  - Blood trace minerals concentrations and oxidative stress in patients with
      obstructive sleep apnea.
AB  - BACKGROUND: Obstructive sleep apnea (OSA) is associated with increased oxidative
      stress. Certain essential trace minerals have shown to play an important role in
      the maintenance of redox homeostasis. We determined the concentrations of trace
      minerals in OSA patients and assessed their relationships to OSA severity as
      indicated by the apnea/ hypopnea index (AHI). METHODS: We enrolled 44 patients
      with newly diagnosed mild to moderate OSA and 20 without OSA. The following
      parameters were measured: polysomnographic values of nocturnal sleep; plasma
      trace minerals zinc (Zn), copper (Cu), iron (Fe), and erythrocyte selenium (Se);
      oxidative stress status; and plasma high-sensitivity C-reactive protein (hs-CRP)
      and tumor necrosis factor-alpha (TNF-alpha). RESULTS: Compared to controls
      matched for age, gender, and body mass index, OSA patients had lower
      concentrations of plasma Zn and erythrocyte Se and higher plasma concentrations
      of Cu and Fe. OSA patients had significantly higher plasma concentrations of hs
      CRP, TNF-alpha, and malondialdehyde (MDA), and lower erythrocyte antioxidant
      enzyme glutathione peroxidase (GPx) and superoxide dismutase activities.
      Significant differences in all the above parameters were also found in patients
      with moderate OSA compared to those with mild OSA. Furthermore, AHI values
      correlated significantly with neck circumference, GPx activity, and MDA, hs-CRP,
      and TNF-alpha concentrations in OSA patients. AHI values were also negatively
      associated with concentrations of plasma Zn and erythrocyte Se, but were
      positively linked to plasma concentrations of Fe and Cu. CONCLUSIONS: Abnormal
      concentrations of these trace minerals may reflect oxidative damage and
      inflammatory response, thus increasing the severity of OSA.

PMID- 24097017
TI  - Are informal carers and community care workers effective in managing malnutrition
      in the older adult community? A systematic review of current evidence.
AB  - BACKGROUND: Enhancing the effectiveness of the community and aged care workforce
      to prevent malnutrition and functional decline is important in reducing hospital
      and aged care facility demand. OBJECTIVE: To investigate the impact of nutrition
      related interventions delivered to or by informal carers and non-clinical
      community care workers on malnutrition-related health outcomes of community
      dwelling older adults (>=65 years). METHODS: Intervention studies were searched
      for using six electronic databases for English-language publications from January
      1980 to 30 May 2012. RESULTS: Nine studies were eligible for inclusion. The
      strength and quality of the evidence was moderate (six studies with level II
      intervention evidence, five with positive quality). Types of interventions used
      were highly varied. The majority of interventions were delivered to informal
      carers (6 studies), with three of these studies also involving older adult care
      recipients. Five interventions were targeted at identifying, preventing and/or
      treating malnutrition specifically (two positive quality, three neutral quality,
      n=2368). As a result of these interventions, nutritional status improved or
      stabilized (two positive quality, two neutral quality, n=2333). No study reported
      an improvement in functional status but two successfully prevented further
      decline in their participants (two neutral quality, n=1097). CONCLUSION:
      Interventions targeted at identifying, preventing and/or treating malnutrition
      were able to improve or prevent decline in nutritional and functional status,
      without increasing informal carer burden. The findings of this review support the
      involvement of non-clinical community care workers and informal carers as part of
      the nutritional care team for community-dwelling older adults.

PMID- 24097018
TI  - Recommendations for ICT use in Alzheimer's disease assessment: Monaco CTAD Expert
      Meeting.
AB  - Alzheimer disease (AD) and other related dementia represent a major challenge for
      health care systems within the aging population. It is therefore important to
      develop better instruments for assessing disease severity and disease progression
      to optimize patient's care and support to care providers, and also provide better
      tools for clinical research. In this area, Information and Communication
      Technologies (ICT) are of particular interest. Such techniques enable accurate
      and standardized assessments of patients' performance and actions in real time
      and real life situations. The aim of this article is to provide basic
      recommendation concerning the development and the use of ICT for Alzheimer's
      disease and related disorders. During he ICT and Mental Health workshop (CTAD
      meeting held in Monaco on the 30th October 2012) an expert panel was set up to
      prepare the first recommendations for the use of ICT in dementia research. The
      expert panel included geriatrician, epidemiologist, neurologist, psychiatrist,
      psychologist, ICT engineers, representatives from the industry and patient
      association. The recommendations are divided into three sections corresponding to
      1/ the clinical targets of interest for the use of ICT, 2/ the conditions, the
      type of sensors and the outputs (scores) that could be used and obtained, 3/
      finally the last section concerns specifically the use of ICT within clinical
      trials. 

PMID- 24097019
TI  - Association of executive function impairment, history of falls and physical
      performance in older adults: a cross-sectional population-based study in eastern
      France.
AB  - OBJECTIVE: To estimate: (1) the association between executive function (EF)
      impairment and falls; and (2) the association of EF impairment on tests of
      physical function used in the evaluation of fall risk. DESIGN: Cross-sectional
      study. SETTING: Thirteen health examination centres in Eastern France.
      PARTICIPANTS: Four thousand four hundred and eighty one community-dwelling older
      adults without dementia aged 65 to 97 years (mean age 71.8+/-5.4, women 47.6%).
      MEASUREMENTS: Participants underwent a comprehensive medical assessment that
      included evaluations of EF using the Clock Drawing Test and of physical
      performance using the Timed Up and Go Test (TUG). Analysis used multivariable
      modified Poisson regression to evaluate the association between impaired EF and
      each of the fall outcomes (any fall, recurrent falls, fall-related injuries).
      Multivariable linear regression was used to evaluate the association between EF
      impairment and performance on the TUG and grip strength. RESULTS: EF impairment,
      assessed using the clock drawing test, was present in 24.9% of participants. EF
      impairment was independently associated with an increased risk of any fall
      (RR=1.13, 95% CI (1.03, 1.25)) and major soft tissue fall-related injury (RR=
      2.42, 95% CI (1.47, 4.00)). Additionally, EF impairment was associated with worse
      performance on the TUG (p<0.0001). CONCLUSIONS: EF impairment among older adults
      without dementia was highly prevalent and was independently associated with an
      increased risk for falls, fall-related injuries and with decreased physical
      function. The use of the Clock Drawing Test is an easy to administer measure of
      EF that can be used routinely in comprehensive fall risk evaluations.

PMID- 24097020
TI  - Direct effects of leisure-time physical activity on walking speed.
AB  - OBJECTIVE: This study quantifies the effects of leisure-time physical activity
      (LTPA) on walking speed independently of body composition in an elderly cohort,
      and in those elderly with metabolic derangements due to age, diabetes, and
      cardiovascular disease (CVD). METHODS: 1655 community-dwelling women and men >55
      years were measured for body composition (lean mass : fat mass ratio, LNFAT) ,
      based on estimated bioelectric impedance by using population-specific prediction
      equations derived from dual-energy x-ray absorptiometry. In addition to LNFAT,
      LTPA, diabetes, CVD, walking speed, and other covariates were measured biannually
      over an 8-year period. LTPA was categorized as <22.5 Mets/week, >= 22.5
      Mets/week, based on public-health recommended guidelines, and LNFAT was
      dichotomized based on its sex-specific median. Direct effects of high vs. low
      LTPA on walking speed were estimated for fixed levels of LNFAT, which represented
      an intermediary variable in the analysis. Stratified estimates of effects were
      obtained using subject status (e.g., age>=75 years, diabetes, CVD) at each visit.
      RESULTS: Walking speed was significantly greater (0.74, 0.75 m/s in women and
      men, respectively) if subjects experienced LTPA >=22.5 Mets/week and > median
      LNFAT, compared with <22.5 Mets/week and <= median LNFAT (0.68, 0.69 m/s). While
      direct effects of LTPA contributed to higher walking speed, none were significant
      in the overall, nor the stratified groups of subjects, of either sex.
      CONCLUSIONS: Walking speed increases with greater LTPA and LNFAT in the elderly,
      but there was no evidence to indicate that walking speed increases from LTPA
      independently of body composition and the metabolic processes it represents.

PMID- 24097021
TI  - Efficacy of fasting and calorie restriction (FCR) on mood and depression among
      ageing men.
AB  - OBJECTIVE: An intervention study on the FCR (Fasting and Calorie Restriction)
      dietary regime was carried out to determine its efficacy in improving mood states
      and depression status among ageing men. SUBJECTS: A total of 32 healthy males
      (Mean+/-SD), aged 59.7+/-6.3 years, with a BMI of 26.7+/-2.2 kg/m2 were recruited
      to the study. METHOD: Participants were randomized to either the FCR group (and
      were instructed to follow a calorie restricted dietary regime with intermittent
      fasting) or to the control group (in which individuals were asked to maintain
      their current lifestyle), for a 3 month period. Mood was assessed using the
      Profile of Mood States and depression was assessed using Beck Depression
      Inventory-II and Geriatric Depression Scale-15 at baseline, week 6 and week 12 of
      the intervention. RESULTS: A total of 31 subjects completed the study (n=16, FCR
      and n=15, control). Significant decreases in tension, anger, confusion and total
      mood disturbance and improvements in vigor were observed in participants in the
      FCR group compared to the control group (p<0.05). No significant changes in mean
      depression scores were observed. Weight, BMI and percent body fat were reduced by
      3.8%, 3.7% and 5.7% respectively in the FCR group. CONCLUSIONS: Our findings show
      that a FCR dietary regime is effective in improving mood states and nutritional
      status among ageing men.

PMID- 24097022
TI  - The therapeutic management of chronic pain in ambulatory care patients aged 65
      and over in France: the S.AGES Cohort. Baseline data.
AB  - OBJECTIVE: The main objective of the S.AGES (Elderly Subjects) cohort study is to
      describe the current therapeutic strategy for chronic pain in non
      institutionalised elderly patients in France. METHODS: In this prospective cohort
      study, non-institutionalised patients aged 65 years and over with chronic pain
      were recruited by general practitioners (GP) across France. All medicinal and non
      medicinal prescriptions were recorded at inclusion and will be followed up over
      3 years via an eCRF. Data recorded at baseline are presented in this paper.
      RESULTS: Two hundred and sixty GPs enrolled 1379 evaluable patients between June
      3rd, 2009 and June 3rd, 2011. Pain was mainly of a mechanical nature, due to
      osteoarthritis or common back pain. 80% of the patients had moderate or severe
      pain. More than a third of patients were treated with a step 1 analgesic (mainly
      paracetamol), and approximately 30% received a step 2 analgesic (23%
      dextropropoxyphene and 40.3% tramadol/paracetamol combination). Only 3% received
      step 3 analgesics; this rate remained low even in patients with severe pain. The
      proportion of patients treated with an antiepileptic was higher in case of
      neuropathic pain. More than 25% of patients did not receive any analgesic
      medication. CONCLUSION: The baseline S.AGES study results exhibit a well-balanced
      therapeutic management of chronic pain by GPs for ambulatory elderly patients.
      Clinicaltrials.org NCT01065909.

PMID- 24097023
TI  - Promoting access to innovation for frail old persons. IAGG (International
      Association of Gerontology and Geriatrics), WHO (World Health Organization) and
      SFGG (Societe Francaise de Geriatrie et de Gerontologie) Workshop--Athens January
      20-21, 2012.
AB  - Frailty tends to be considered as a major risk for adverse outcomes in older
      persons, but some important aspects remain matter of debate. OBJECTIVES: The
      purpose of this paper is to present expert's positions on the main aspects of the
      frailty syndrome in the older persons. PARTICIPANTS: Workshop organized by
      International Association of Gerontology and Geriatrics (IAGG), World Health
      Organization (WHO) and Societe Francaise de Geriatrie et de Gerontologie (SFGG).
      RESULTS: Frailty is widely recognized as an important risk factor for adverse
      health outcomes in older persons. This can be of particular value in evaluating
      non-disabled older persons with chronic diseases but today no operational
      definition has been established. Nutritional status, mobility, activity,
      strength, endurance, cognition, and mood have been proposed as markers of
      frailty. Another approach calculates a multidimensional score ranging from "very
      fit" to "severely frail", but it is difficult to apply into the medical practice.
      Frailty appears to be secondary to multiple conditions using multiple pathways
      leading to a vulnerability to a stressor. Biological (inflammation, loss of
      hormones), clinical (sarcopenia, osteoporosis etc.), as well as social factors
      (isolation, financial situation) are involved in the vulnerability process. In
      clinical practice, detection of frailty is of major interest in oncology because
      of the high prevalence of cancer in older persons and the bad tolerance of the
      drug therapies. Presence of frailty should also be taken into account in the
      definition of the cardiovascular risks in the older population. The experts of
      the workshop have listed the points reached an agreement and those must to be a
      priority for improving understanding and use of frailty syndrome in practice.
      CONCLUSION: Frailty in older adults is a syndrome corresponding to a
      vulnerability to a stressor. Diagnostic tools have been developed but none can
      integrate at the same time the large spectrum of factors and the simplicity asked
      by the clinical practice. An agreement with an international common definition is
      necessary to develop screening and to reduce the morbidity in older persons.

PMID- 24097024
TI  - Who is at risk of long hospital stay among patients admitted to geriatric acute
      care unit? Results from a prospective cohort study.
AB  - OBJECTIVE: (1) To confirm that vitamin D deficiency, defined as serum 25
      hydroxyvitamin D (25OHD) concentration < 25 nmol/L, was associated with long
      length-of-stay (LOS) among older inpatients admitted to geriatric acute care
      unit; and (2) to examine which combination of risk factors of longer LOS
      including vitamin D deficiency best predicted longer LOS. STUDY DESIGN AND
      SETTING: Based on a prospective cohort study with a 25-day follow-up on average,
      531 consecutive older inpatients (mean age 85.0+/-7.2 years, 59.1% women)
      admitted to the geriatric acute care unit of Angers University Hospital, France,
      were included. RESULTS: Linear regression models showed that male gender
      (P<0.025), delirium (P<0.015) and vitamin D deficiency (P<0.001) were
      independently associated with a longer LOS. The highest risk of a longer LOS was
      shown while combining vitamin D deficiency with male gender (Odds ratio (OR)=3.70
      with P< 0.001). The risk increased significantly while delirium was associated
      with these two baseline characteristics (OR=4.76 with P=0.001). Kaplan-Meier
      distributions of discharge differed significantly between participants who had or
      not the combination of the 3 criteria (P<0.007). CONCLUSIONS: Vitamin D
      deficiency, delirium and male gender were significant risk factors for a longer
      LOS in the studied sample of older inpatients.

PMID- 24097025
TI  - Inter-rater reliability of the assessment of adverse drug reactions in the
      hospitalised elderly.
AB  - BACKGROUND: The identification and assessment of adverse drug reactions (ADRs) is
      very challenging especially among the older person. Inter observer reliability of
      an ADR classification system by different healthcare providers is vital to
      establish the validity of the reaction. OBJECTIVE: To assess the inter-rater
      reliability of an ADR classification system in hospitalised elderly patients and
      to investigate the differences in reliability by different professions. METHODS:
      From a cohort of 330 elderly patients, patients who experienced a suspected
      medication related incident (n=87) were selected. The data were analysed by four
      healthcare professionals (2 pharmacists and 2 physicians) who independently
      classified the events into event type, types of adverse drug reactions, severity
      and preventability after a standardised induction based on previously published
      criteria. Fleiss' kappa was used to assess the level of agreement between the
      four raters. The difference in level of agreement between the professions was
      assessed using the weighted least-squares approach for comparing correlated kappa
      of Barnhart et al. RESULTS: Pharmacists and physicians showed high agreement in
      the identification and on the type and causality of ADRs. However there was lower
      (moderate) agreement for the severity (kappa = 0.61) and preventability of ADR
      (kappa = 0.48). Statistically significant differences were also noted between the
      professions; pharmacists have higher agreement in the classification of
      preventability (p=0.03) whereas the physicians pairs showed stronger agreement
      for classifying severity (p<0.001). CONCLUSION: Despite the high agreement in the
      identification, type and causality of ADRs, physicians and pharmacists have
      difficulties in classifying preventability and severity in a reliable way. A
      multi-disciplinary approach would enable each profession to share their expert
      knowledge in order to facilitate better or safer patient care.

PMID- 24097026
TI  - Nutrition and the biology of human ageing: proceedings of the Ninth Nestle
      International Nutrition Symposium.

PMID- 24097027
TI  - Nutrition and the biology of human ageing: ageing in the human population.

PMID- 24097028
TI  - Nutrition and the biology of human ageing: molecular mechanisms underlying
      ageing.

PMID- 24097029
TI  - Nutrition and the biology of human ageing: bone health and osteoporosis /
      sarcopenia / immune deficiency.

PMID- 24097030
TI  - Nutrition and the biology of human ageing: cognitive decline/food intake and
      caloric restriction.

PMID- 24097031
TI  - Are European countries prepared for the next big heat-wave?
AB  - BACKGROUND: Heat-waves present severe dangers to populations' health. Due to
      climate change, an increase in the frequency and intensity of heat-waves is to be
      expected. Public health measures to prevent negative health effects have been
      developed in several member states of the World Health Organization (WHO)
      European Region over the past decade. METHODS: This study presents the first
      comprehensive assessment of the development of heat preparedness planning in WHO
      European Region member states, using a unique methodology based on criteria
      developed and pre-tested by the WHO. This indicator-based approach is based on
      eight core elements that are crucial components of heat-health action plans.
      RESULTS: Of 53 member states of the WHO European Region, 51 countries were
      included in the evaluation. Results show that 18 countries have developed heat
      health action plans, whereas 33 others have not. The plans developed so far vary
      in the degree of comprehensiveness with regard to the core elements. Gaps in
      terms of plan coverage have predominantly been identified in the areas of
      (intersectorial) long-term measures, surveillance and plan evaluation.
      CONCLUSIONS: For better preparedness, it can be advocated for further improving,
      developing and implementing heat-wave preparedness planning and response in
      European countries. A focus should be placed on developing all elements and
      strong intersectorial coordination and cooperation as well as the successful
      implementation of surveillance and evaluation measures.

PMID- 24097032
TI  - Epigenetic histone methylation regulates transforming growth factor beta-1
      expression following bile duct ligation in rats.
AB  - BACKGROUND: Multiple mechanisms contribute to the liver fibrosis following
      cholestasis. Recent research has focused on the role of transforming growth
      factor beta-1 (TGF-beta1) in the progression of fibrosis. The aim of our study is
      to examine the role of epigenetic chromatin marks, such as histone H3 lysine
      methylation (H3Kme), in bile duct ligation (BDL)-induced TGF-beta1 gene
      expression in rat liver. METHODS: Time course of methylated-histone H3 and SET7/9
      recruitment were determined by chromatin immunoprecipitation in livers from BDL
      rats on days 1, 4, 9 and 14. Levels of TGF-beta1 and SET7/9 were determined by
      western blots. The effect of SET7/9 knockdown on BDL-induced expression of TGF
      beta1, serum enzymes and liver collagen content was studied in vivo. RESULTS:
      Results showed that BDL increased the expression of the TGF beta-1. Increased
      levels of active chromatin marks (H3K4me1, H3K4me2, and H3K4me3) and decreased
      levels of repressive marks (H3K9me2 and H3K9me3) in TGF-beta1 promoter
      accompanied the changes in expression of the TGF beta-1. BDL also increased
      expression of the H3K4 methyltransferase SET7/9 and recruitment to the promoter.
      SET7/9 gene knockdown with siRNAs significantly attenuated BDL-induced TGF-beta1
      gene expression, serum enzymes and liver collagen content. CONCLUSIONS: Taken
      together, these results show the functional role of epigenetic chromatin histone
      H3Kme in BDL-induced TGF-beta1 expression. Pharmacologic and other therapies that
      reverse these modifications could have potential hepatoprotective effects for BDL
      induced cirrhosis.

PMID- 24097033
TI  - CD36: linking lipids to the NLRP3 inflammasome, atherogenesis and
      atherothrombosis.

PMID- 24097034
TI  - Critical role of butyrophilin 3A1 in presenting prenyl pyrophosphate antigens to
      human gammadelta T cells.

PMID- 24097035
TI  - rFliC prolongs allograft survival in association with the activation of recipient
      Tregs in a TLR5-dependent manner.
AB  - Allorejection remains an obstacle for successful organ transplantation. Although
      different types of immunosuppressive agents are effective for controlling
      rejection and prolonging graft survival, drug treatment is limited because of
      side effects and toxicity. Therefore, it is necessary and urgent to identify new
      candidate drugs for inducing allotolerance. Recently, it has been reported that
      bacterial flagellin induces the immunosuppressive activity of regulatory T cells
      (Tregs) in humans in vitro. In the present study, we analyzed the effects of
      recombinant flagellin (rFliC) on allograft survival and explored the underlying
      mechanisms associated with the activation of recipient Tregs in a murine skin
      allotransplantation model. The results showed that rFliC administration (3 mg/kg,
      once per day for 3 days, i.p.) prolonged allograft survival (mean survival time:
      18.4+/-1.1 days) compared to the control group (10+/-0.7 days, P<0.01).
      Additionally, higher positive expression of Toll-like receptor 5 (TLR5) was
      detected within the allograft administered with rFliC. The frequency of
      CD4(+)CD25(+)Foxp3(+) Tregs; the expression of Treg-related factors TLR5, Foxp3,
      TGF-beta1 and IL-10; and the proliferation and suppression of Tregs were
      increased following rFliC administration compared to the control. Moreover, the
      increased expression of tolerance-related molecules and the proliferation of
      Tregs induced by rFliC were attenuated by an anti-TLR5 blocking antibody both in
      vivo and in vitro. In conclusion, rFliC administration prolongs the survival of
      allografts, which is associated with the activation of recipient Tregs in a TLR5
      dependent manner. rFliC may be a new candidate for anti-allorejection therapy. 

PMID- 24097036
TI  - A fat story-antigen presentation by butyrophilin 3A1 to gammadelta T cells.

PMID- 24097037
TI  - Ultrafast demagnetization enhancement in CoFeB/MgO/CoFeB magnetic tunneling
      junction driven by spin tunneling current.
AB  - The laser-induced ultrafast demagnetization of CoFeB/MgO/CoFeB magnetic tunneling
      junction is exploited by time-resolved magneto-optical Kerr effect (TRMOKE) for
      both the parallel state (P state) and the antiparallel state (AP state) of the
      magnetizations between two magnetic layers. It was observed that the
      demagnetization time is shorter and the magnitude of demagnetization is larger in
      the AP state than those in the P state. These behaviors are attributed to the
      ultrafast spin transfer between two CoFeB layers via the tunneling of hot
      electrons through the MgO barrier. Our observation indicates that ultrafast
      demagnetization can be engineered by the hot electrons tunneling current. It
      opens the door to manipulate the ultrafast spin current in magnetic tunneling
      junctions. 

PMID- 24097038
TI  - Membrane potential correlates of sensory perception in mouse barrel cortex.
AB  - Neocortical activity can evoke sensory percepts, but the cellular mechanisms
      remain poorly understood. We trained mice to detect single brief whisker stimuli
      and report perceived stimuli by licking to obtain a reward. Pharmacological
      inactivation and optogenetic stimulation demonstrated a causal role for the
      primary somatosensory barrel cortex. Whole-cell recordings from barrel cortex
      neurons revealed membrane potential correlates of sensory perception. Sensory
      responses depended strongly on prestimulus cortical state, but both slow-wave and
      desynchronized cortical states were compatible with task performance. Whisker
      deflection evoked an early (<50 ms) reliable sensory response that was encoded
      through cell-specific reversal potentials. A secondary late (50-400 ms)
      depolarization was enhanced on hit trials compared to misses. Optogenetic
      inactivation revealed a causal role for late excitation. Our data reveal dynamic
      processing in the sensory cortex during task performance, with an early sensory
      response reliably encoding the stimulus and later secondary activity contributing
      to driving the subjective percept. 

PMID- 24097039
TI  - Non-epithelial stem cells and cortical interneuron production in the human
      ganglionic eminences.
AB  - GABAergic cortical interneurons underlie the complexity of neural circuits and
      are particularly numerous and diverse in humans. In rodents, cortical
      interneurons originate in the subpallial ganglionic eminences, but their
      developmental origins in humans are controversial. We characterized the
      developing human ganglionic eminences and found that the subventricular zone
      (SVZ) expanded massively during the early second trimester, becoming densely
      populated with neural stem cells and intermediate progenitor cells. In contrast
      with the cortex, most stem cells in the ganglionic eminence SVZ did not maintain
      radial fibers or orientation. The medial ganglionic eminence exhibited unique
      patterns of progenitor cell organization and clustering, and markers revealed
      that the caudal ganglionic eminence generated a greater proportion of cortical
      interneurons in humans than in rodents. On the basis of labeling of newborn
      neurons in slice culture and mapping of proliferating interneuron progenitors, we
      conclude that the vast majority of human cortical interneurons are produced in
      the ganglionic eminences, including an enormous contribution from non-epithelial
      SVZ stem cells. 

PMID- 24097040
TI  - Transcriptional repression of Bmp2 by p21(Waf1/Cip1) links quiescence to neural
      stem cell maintenance.
AB  - Relative quiescence and self renewal are defining features of adult stem cells,
      but their potential coordination remains unclear. Subependymal neural stem cells
      (NSCs) lacking cyclin-dependent kinase (CDK) inhibitor (CKI) 1a (p21) exhibit
      rapid expansion that is followed by their permanent loss later in life. Here we
      demonstrate that transcription of the gene encoding bone morphogenetic protein 2
      (Bmp2) in NSCs is under the direct negative control of p21 through actions that
      are independent of CDK. Loss of p21 in NSCs results in increased levels of
      secreted BMP2, which induce premature terminal differentiation of multipotent
      NSCs into mature non-neurogenic astrocytes in an autocrine and/or paracrine
      manner. We also show that the cell-nonautonomous p21-null phenotype is modulated
      by the Noggin-rich environment of the subependymal niche. The dual function that
      we describe here provides a physiological example of combined cell-autonomous and
      cell-nonautonomous functions of p21 with implications in self renewal, linking
      the relative quiescence of adult stem cells to their longevity and potentiality. 

PMID- 24097041
TI  - Subcortical origins of human and monkey neocortical interneurons.
AB  - Cortical GABAergic inhibitory interneurons have crucial roles in the development
      and function of the cerebral cortex. In rodents, nearly all neocortical
      interneurons are generated from the subcortical ganglionic eminences. In humans
      and nonhuman primates, however, the developmental origin of neocortical GABAergic
      interneurons remains unclear. Here we show that the expression patterns of
      several key transcription factors in the developing primate telencephalon are
      very similar to those in rodents, delineating the three main subcortical
      progenitor domains (the medial, lateral and caudal ganglionic eminences) and the
      interneurons tangentially migrating from them. On the basis of the continuity of
      Sox6, COUP-TFII and Sp8 transcription factor expression and evidence from cell
      migration and cell fate analyses, we propose that the majority of primate
      neocortical GABAergic interneurons originate from ganglionic eminences of the
      ventral telencephalon. Our findings reveal that the mammalian neocortex shares
      basic rules for interneuron development, substantially reshaping our
      understanding of the origin and classification of primate neocortical
      interneurons. 

PMID- 24097042
TI  - Origin and effect of phototransduction noise in primate cone photoreceptors.
AB  - Noise in the responses of cone photoreceptors sets a fundamental limit on visual
      sensitivity, yet the origin of noise in mammalian cones and its relation to
      behavioral sensitivity are poorly understood. Our work here on primate cones
      improves understanding of these issues in three ways. First, we found that cone
      noise was not dominated by spontaneous photopigment activation or by quantal
      fluctuations in photon absorption, but was instead dominated by other sources,
      namely channel noise and fluctuations in cyclic GMP. Second, adaptation in cones,
      unlike that in rods, affected signal and noise differently. This difference helps
      to explain why thresholds for rod- and cone-mediated signals have different
      dependencies on background light level. Third, past estimates of noise in
      mammalian cones are too high to explain behavioral sensitivity. Our measurements
      indicate a lower level of cone noise and therefore help to reconcile
      physiological and behavioral estimates of cone noise and sensitivity. 

PMID- 24097043
TI  - Dual origins of functionally distinct O-LM interneurons revealed by differential
      5-HT(3A)R expression.
AB  - Forebrain circuits rely upon a relatively small but remarkably diverse population
      of GABAergic interneurons to bind and entrain large principal cell assemblies for
      network synchronization and rhythmogenesis. Despite the high degree of
      heterogeneity across cortical interneurons, members of a given subtype typically
      exhibit homogeneous developmental origins, neuromodulatory response profiles,
      morphological characteristics, neurochemical signatures and electrical features.
      Here we report a surprising divergence among hippocampal oriens-lacunosum
      moleculare (O-LM) projecting interneurons that have hitherto been considered a
      homogeneous cell population. Combined immunocytochemical, anatomical and
      electrophysiological interrogation of Htr3a-GFP and Nkx2-1-cre:RCE mice revealed
      that O-LM cells parse into a caudal ganglionic eminence-derived subpopulation
      expressing 5-HT(3A) receptors (5-HT(3A)Rs) and a medial ganglionic eminence
      derived subpopulation lacking 5-HT(3A)Rs. These two cohorts differentially
      participate in network oscillations, with 5-HT(3A)R-containing O-LM cell
      recruitment dictated by serotonergic tone. Thus, members of a seemingly uniform
      interneuron population can exhibit unique circuit functions and neuromodulatory
      properties dictated by disparate developmental origins.

PMID- 24097045
TI  - Neon color spreading in dynamic displays: temporal factors.
AB  - When a red star is placed in the middle of an Ehrenstein figure so as to be
      collinear with the surrounding black rays, a reddish veil is perceived to fill
      the white center. This is called neon color spreading. To better understand the
      processes that give rise to this phenomenon, we studied the temporal properties
      of the effect. Specifically, we presented a "sustained" black Ehrenstein figure
      (rays) for 600 ms and a "transient" red star for 48 ms, or the converse pattern,
      at various stimulus onset asynchronies (-100-700 ms) and asked subjects to
      compare the strength of the neon color in the test stimulus to that of a
      reference pattern in which the transient star had an onset asynchrony of 300 ms.
      Additional exposure durations of 24 and 96 ms were used for each transient
      stimulus in order to study the effect of temporal integration. Simultaneity of
      the on- and off-transients of the star and the Ehrenstein rays were found to
      optimize neon color spreading, especially when both stimuli terminated together.
      Longer exposure durations of the transient stimulus up to 96 ms further improved
      the effect. Neon color spreading was much reduced when the transient stimulus was
      presented soon after the beginning of the sustained stimulus, with a gradual
      build-up towards the end. These results emphasize the importance of stimulus
      onset asynchrony (SOA) and stimulus termination asynchrony (STA) for the
      perception of neon color spreading. 

PMID- 24097044
TI  - A disinhibitory circuit mediates motor integration in the somatosensory cortex.
AB  - The influence of motor activity on sensory processing is crucial for perception
      and motor execution. However, the underlying circuits are not known. To unravel
      the circuit by which activity in the primary vibrissal motor cortex (vM1)
      modulates sensory processing in the primary somatosensory barrel cortex (S1), we
      used optogenetics to examine the long-range inputs from vM1 to the various
      neuronal elements in S1. We found that S1-projecting vM1 pyramidal neurons
      strongly recruited vasointestinal peptide (VIP)-expressing GABAergic
      interneurons, a subset of serotonin receptor-expressing interneurons. These VIP
      interneurons preferentially inhibited somatostatin-expressing interneurons,
      neurons that target the distal dendrites of pyramidal cells. Consistent with this
      vM1-mediated disinhibitory circuit, the activity of VIP interneurons in vivo
      increased and that of somatostatin interneurons decreased during whisking. These
      changes in firing rates during whisking depended on vM1 activity. Our results
      suggest previously unknown circuitry by which inputs from motor cortex influence
      sensory processing in sensory cortex. 

PMID- 24097046
TI  - Depth compression based on mis-scaling of binocular disparity may contribute to
      angular expansion in perceived optical slant.
AB  - Three studies, involving a total of 145 observers examined quantitative theories
      of the overestimation of perceived optical slant. The first two studies
      investigated the depth/width anisotropies on positive and negative slant in both
      pitch and yaw at 2 and 8 m using calibrated immersive virtual environments.
      Observers made judgments of the relative lengths of extents that were frontal
      with those that were in depth. The physical aspect ratio that was perceived as
      1:1 was determined for each slant. The observed anisotropies can be modeled by
      assuming overestimation in perceived slant. Three one-parameter slant perception
      models (angular expansion, affine depth compression caused by mis-scaling of
      binocular disparity, and intrinsic bias) were compared. The angular expansion and
      the affine depth compression models provided significantly better fits to the
      aspect ratio data than the intrinsic bias model did. The affine model required
      depth compression at the 2 m distance; however, that was much more than the depth
      compression measured directly in the third study using the same apparatus. The
      present results suggest that depth compression based on mis-scaling of binocular
      disparity may contribute to slant overestimation, especially as viewing distance
      increases, but also suggest that a functional rather than mechanistic account may
      be more appropriate for explaining biases in perceived slant in near space. 

PMID- 24097047
TI  - Precise chronology of differentiation of developing human primary dentition.
AB  - While correlation of developmental stage with embryonic age of the human primary
      dentition has been well documented, the available information regarding the
      differentiation timing of the primary teeth was largely based on the observation
      of initial mineralization and varies significantly. In this study, we aimed to
      document precise differentiation timing of the developing human primary
      dentition. We systematically examined the expression of odontogenic
      differentiation markers along with the formation of mineralized tissue in each
      developing maxillary and mandibular teeth from human embryos with well-defined
      embryonic age. We show that, despite that all primary teeth initiate development
      at the same time, odontogenic differentiation begins in the maxillary incisors at
      the 15th week and in the mandibular incisors at the 16th week of gestation,
      followed by the canine, the first primary premolar, and the second primary
      premolar at a week interval sequentially. Despite that the mandibular primary
      incisors erupt earlier than the maxillary incisors, this distal to proximal
      sequential differentiation of the human primary dentition coincides in general
      with the sequence of tooth eruption. Our results provide an accurate chronology
      of odontogenic differentiation of the developing human primary dentition, which
      could be used as reference for future studies of human tooth development. 

PMID- 24097048
TI  - Reaction pathways and free energy profiles for spontaneous hydrolysis of urea and
      tetramethylurea: unexpected substituent effects.
AB  - It has been difficult to directly measure the spontaneous hydrolysis rate of urea
      and, thus, 1,1,3,3-tetramethylurea (Me4U) was used as a model to determine the
      "experimental" rate constant for urea hydrolysis. The use of Me4U was based on an
      assumption that the rate of urea hydrolysis should be 2.8 times that of Me4U
      hydrolysis because the rate of acetamide hydrolysis is 2.8 times that of N,N
      dimethyl-acetamide hydrolysis. The present first-principles electronic-structure
      calculations on the competing non-enzymatic hydrolysis pathways have demonstrated
      that the dominant pathway is the neutral hydrolysis via the CN addition for both
      urea (when pH < ~11.6) and Me4U (regardless of pH), unlike the non-enzymatic
      hydrolysis of amides where alkaline hydrolysis is dominant. Based on the
      computational data, the substituent shift of the free energy barrier calculated
      for the neutral hydrolysis is remarkably different from that for the alkaline
      hydrolysis, and the rate constant for the urea hydrolysis should be ~1.3 * 10(9)
      fold lower than that (4.2 * 10(-12) s(-1)) measured for the Me4U hydrolysis. As a
      result, the rate enhancement and catalytic proficiency of urease should be 1.2 *
      10(25) and 3 * 10(27) M(-1), respectively, suggesting that urease surpasses
      proteases and all other enzymes in its power to enhance the rate of reaction. All
      of the computational results are consistent with available experimental data for
      Me4U, suggesting that the computational prediction for urea is reliable.

PMID- 24097049
TI  - Agrobacterium-mediated transformation of promising oil-bearing marine algae
      Parachlorella kessleri.
AB  - Parachlorella kessleri is a unicellular alga which grows in fresh as well as
      marine water and is commercially important as biomass/lipid feedstock and in
      bioremediation. The present study describes the successful transformation of
      marine P. kessleri with the help of Agrobacterium tumefaciens. Transformed marine
      P. kessleri was able to tolerate more than 10 mg l(-1) hygromycin concentration.
      Co-cultivation conditions were modulated to allow the simultaneous growth of both
      marine P. kessleri and A. tumefaciens. For co-cultivation, P. kessleri was
      shifted from Walne's to tris acetate phosphate medium to reduce the antibiotic
      requirement during selection. In the present study, the transfer of T-DNA was
      successful without using acetosyringone. Biochemical and genetic analyses were
      performed for expression of transgenes by GUS assay and PCR in transformants.
      Establishment of this protocol would be useful in further genetic modification of
      oil-bearing Parachlorella species. 

PMID- 24097050
TI  - Effect of unilateral posterior crossbite and unilateral cleft lip and palate on
      vertical mandibular asymmetry.
AB  - OBJECTIVE: Evaluate condylar, ramal, and condylar plus ramal vertical mandibular
      asymmetry in patients with unilateral posterior crossbite (UPCB) and in patients
      with unilateral cleft lip and palate (UCLP) compared with subjects having normal
      occlusion. DESIGN: This cross-sectional study evaluated panoramic radiographs of
      three groups of subjects: UPCB, 20 patients; UCLP, 20 patients; and normal
      occlusion sample, 20 subjects. All subjects were picked at random from Rey Juan
      Carlos University, Madrid, and all films were traced and measured manually by the
      same author. RESULTS: Kruskal-Wallis test revealed no statistically significant
      differences (P < 0.05) in condylar asymmetry index (CAI), ramal asymmetry index
      (RAI), and condylar plus ramal asymmetry index (C + RAI) among the three groups.
      The average CAI for group UPCB was 9.03 +/- 7.65; 8.03 +/- 6.89 for group UCLP;
      6.93 +/- 9.87 for normal group. Mean RAI for group UPCB was 2.53 +/- 2.52; 2.61
      +/- 1.22 for group UCLP; 2.65 +/- 1.90 for normal group. CONCLUSIONS: Condylar
      asymmetry was observed in all three groups (UPCB, UCLP and normal occlusion)
      because condylar asymmetry indexes were higher in each group at the 3 %
      threshold. No statistically significant differences were found among the three
      study groups for any of the asymmetry indexes.

PMID- 24097051
TI  - Impact of familial risk and mammography screening on prognostic indicators of
      breast disease among women from the Ontario site of the Breast Cancer Family
      Registry.
AB  - Although several studies have found screen-detected cancers in women with
      familial breast cancer risk have favorable prognostic features compared with
      symptomatic cancers, the impact of level of familial risk is unknown. A cohort of
      899 first-degree female relatives of cases of breast cancer from the Ontario site
      of the Breast Cancer Family Registry was followed for 2 years. Logistic
      regression analyses compared diagnoses of breast cancer or benign breast disease
      (BBD) between women at high (n = 258, 28.7 %) versus low/moderate (n = 641, 71.3
      %) familial risk. Similar analyses compared prognostic features of invasive
      cancers and BBD by level of familial risk and mammography screening status. Among
      899 women, 44 (4.9 %) were diagnosed with invasive breast cancer and/or ductal
      carcinoma in situ, and 56 (6.2 %) with BBD. Women with high familial risk were
      significantly more likely to be diagnosed with breast cancer [odds ratio (OR) =
      2.84, 95 % confidence interval (CI) 1.50-5.38] than low/moderate risk women,
      particularly if diagnosed at age >=50 (OR = 2.99, 95 % CI 1.37-6.56) or screened
      with mammography (OR = 3.33, 95 % CI 1.54-7.18). High risk women were more likely
      to be diagnosed with BBD (OR = 1.94, 95 % CI 1.03-3.66). Level of familial risk
      was not associated with prognostic features. Cancers among unscreened women were
      larger (OR = 9.72, 95 % CI 1.01-93.61) and diagnosed at stage II or above (OR =
      7.80, 95 % CI 1.18-51.50) compared with screen-detected cancers. Screening
      mammography may be effective for women with a first-degree family history of
      breast cancer, irrespective of level of familial risk.

PMID- 24097052
TI  - Cyclo(L-Pro-D-Arg): a new antibacterial and antitumour diketopiperazine from
      Bacillus cereus associated with a rhabditid entomopathogenic.
AB  - In continuation of our search for new antimicrobial secondary metabolites from
      Bacillus cereus associated with rhabditid entomopathogenic nematode, a new
      microbial diketopiperazine, cyclo(L-Pro-D-Arg), was isolated from the ethyl
      acetate extract of fermented modified nutrient broth. The chemical structures of
      the isolated compounds were identified based on their 1D, 2D NMR and high
      resolution electrospray ionisation-mass spectroscopy data. Antibacterial activity
      of the compound was determined by minimum inhibitory concentration and disc
      diffusion method against medically important bacteria, and the compound was
      recorded to have significant antibacterial activity against test bacteria. The
      highest activity was recorded against Klebsiella pneumoniae (1 MUg/mL). Cyclo(L
      Pro-D-Arg) was recorded to have significant antitumor activity against HeLa cells
      (IC50 value 50 MUg/mL), and this compound was recorded to have no cytotoxicity
      against normal monkey kidney cells (VERO) up to 100 MUg/mL). To the best of our
      knowledge, this is the first time that cyclo(L-Pro-D-Arg) has been isolated from
      a microbial natural source.

PMID- 24097053
TI  - An easy, rapid and inexpensive method to monitor tributyltin (TBT) toxicity in
      the laboratory.
AB  - Tributyltin (TBT) contamination remains a major problem worldwide. Many
      laboratories are committed to the development of remediation methodologies that
      could help reduce the negative impact of this compound in the environment.
      Furthermore, it is important to have at hand simple methodologies for evaluating
      TBT toxicity in the laboratory, besides the use of complex and costly analytical
      instrumentation. With that purpose, a method was adapted that is based on the
      inhibition of growth of an indicator strain, Micrococcus luteus ATCC 9341, under
      TBT. Different types of matrices, of TBT concentrations and sample treatments
      were tested. The results herein reported show that the bioassay method can be
      applied for both aqueous and soil samples and also for a high range of TBT
      concentrations (at least up to 500 MUmol/L). Besides being cheap and easy to
      perform, it can be performed in any laboratory. Additionally, one possible
      application of the method to monitor TBT degradation is presented as an example.

PMID- 24097054
TI  - Near-field spatial mapping of strongly interacting multiple plasmonic infrared
      antennas.
AB  - Near-field dipolar plasmon interactions of multiple infrared antenna structures
      in the strong coupling limit are studied using scattering-type scanning near
      field optical microscope (s-SNOM) and theoretical finite-difference time-domain
      (FDTD) calculations. We monitor in real-space the evolution of plasmon dipolar
      mode of a stationary antenna structure as multiple resonantly matched dipolar
      plasmon particles are closely approaching it. Interparticle separation, length
      and polarization dependent studies show that the cross geometry structure favors
      strong interparticle charge-charge, dipole-dipole and charge-dipole Coulomb
      interactions in the nanometer scale gap region, which results in strong field
      enhancement in cross-bowties and further allows these structures to be used as
      polarization filters. The nanoscale local field amplitude and phase maps show
      that due to strong interparticle Coulomb coupling, cross-bowtie structures
      redistribute and highly enhance the out-of-plane (perpendicular to the plane of
      the sample) plasmon near-field component at the gap region relative to ordinary
      bowties. 

PMID- 24097058
TI  - Hepatitis and liver disease knowledge and preventive practices among health
      workers in Mexico: a cross-sectional study.
AB  - OBJECTIVES: To assess the knowledge and preventive practices regarding hepatitis
      and liver disease among a sample of participants in the Mexican Health Worker
      Cohort Study. METHODS: The study population consisted of 892 participants from
      Cuernavaca, Mexico. Demographic characteristics, knowledge about hepatitis B,
      hepatitis C, and liver disease in general, as well as information about
      prevention practices were obtained from self-reported questionnaires.
      Participants were grouped into categories that were created using information
      about their professional background and patient contact status. Knowledge and
      prevention practices were compared within these categories. RESULTS: Inadequate
      levels of knowledge and preventive practices were found, even within the more
      highly educated group. Nearly 57 % of the participants had inadequate knowledge
      about liver disease in general, while 76 and 79 % had inadequate knowledge about
      Hepatitis B virus (HBV) and Hepatitis C virus (HCV), respectively. For general
      liver disease, the mean knowledge score increased significantly with education,
      history of HCV screening, and low alcohol consumption. CONCLUSIONS: Health
      workers should be better educated about hepatitis and liver disease so they can
      reduce their own risk and share their knowledge of how to prevent liver disease
      with patients.

PMID- 24097059
TI  - Individual differences in the anterior insula are associated with the likelihood
      of financially helping versus harming others.
AB  - The neural basis of individual differences in positive and negative social
      decisions and behaviors in healthy populations is yet undetermined. Recent work
      has focused on the potential role of the anterior insula in guiding social and
      nonsocial decision making, but the specific nature of its activation during such
      decision making remains unclear. To identify the neural regions mediating
      individual differences in helpful and harmful decisions and to assess the nature
      of insula activation during such decisions, in the present study we used a novel
      fMRI task featuring intentional and unintentional decisions to financially harm
      or help persons in need. Based on a whole-brain, unbiased approach, our findings
      indicate that individual differences in dorsal anterior insula, anterior
      cingulate cortex (ACC), and right temporo-parietal junction activation are
      associated with behavioral tendencies to financially harm or help another.
      Furthermore, activity in the dorsal anterior insula and ACC was greatest during
      unintended outcomes, whether these were gains or losses for a charity or for
      oneself, supporting models of the role of these regions in salience prediction
      error signaling. Together, the results suggest that individual differences in
      risk anticipation, as reflected in the dorsal anterior insula and dorsal ACC,
      guide social decisions to refrain from harming others. 

PMID- 24097060
TI  - Structural basis for the MukB-topoisomerase IV interaction and its functional
      implications in vivo.
AB  - Chromosome partitioning in Escherichia coli is assisted by two interacting
      proteins, topoisomerase (topo) IV and MukB. MukB stimulates the relaxation of
      negative supercoils by topo IV; to understand the mechanism of their action and
      to define this functional interplay, we determined the crystal structure of a
      minimal MukB-topo IV complex to 2.3 A resolution. The structure shows that the so
      called 'hinge' region of MukB forms a heterotetrameric assembly with a C-terminal
      DNA binding domain (CTD) on topo IV's ParC subunit. Biochemical studies show that
      the hinge stimulates topo IV by competing for a site on the CTD that normally
      represses activity on negatively supercoiled DNA, while complementation tests
      using mutants implicated in the interaction reveal that the cellular dependency
      on topo IV derives from a joint need for both strand passage and MukB binding.
      Interestingly, the configuration of the MukB.topo IV complex sterically
      disfavours intradimeric interactions, indicating that the proteins may form
      oligomeric arrays with one another, and suggesting a framework by which MukB and
      topo IV may collaborate during daughter chromosome disentanglement. 

PMID- 24097062
TI  - The force and effect of cell proliferation.

PMID- 24097061
TI  - A novel non-coding RNA lncRNA-JADE connects DNA damage signalling to histone H4
      acetylation.
AB  - A prompt and efficient DNA damage response (DDR) eliminates the detrimental
      effects of DNA lesions in eukaryotic cells. Basic and preclinical studies suggest
      that the DDR is one of the primary anti-cancer barriers during tumorigenesis. The
      DDR involves a complex network of processes that detect and repair DNA damage, in
      which long non-coding RNAs (lncRNAs), a new class of regulatory RNAs, may play an
      important role. In the current study, we identified a novel lncRNA, lncRNA-JADE,
      that is induced after DNA damage in an ataxia-telangiectasia mutated (ATM)
      dependent manner. LncRNA-JADE transcriptionally activates Jade1, a key component
      in the HBO1 (human acetylase binding to ORC1) histone acetylation complex.
      Consequently, lncRNA-JADE induces histone H4 acetylation in the DDR. Markedly
      higher levels of lncRNA-JADE were observed in human breast tumours in comparison
      with normal breast tissues. Knockdown of lncRNA-JADE significantly inhibited
      breast tumour growth in vivo. On the basis of these results, we propose that
      lncRNA-JADE is a key functional link that connects the DDR to histone H4
      acetylation, and that dysregulation of lncRNA-JADE may contribute to breast
      tumorigenesis. 

PMID- 24097063
TI  - Neonatal hearing screening of high-risk infants using automated auditory
      brainstem response: a retrospective analysis of referral rates.
AB  - OBJECTIVE: The past decade has seen the widespread introduction of universal
      neonatal hearing screening (UNHS) programmes worldwide. Regrettably, such a
      programme is only now in the process of nationwide implementation in the Republic
      of Ireland and has been largely restricted to one screening modality for initial
      testing; namely transient evoked otoacoustic emissions (TEOAE). The aim of this
      study is to analyse the effects of employing a different screening protocol which
      utilises an alternative initial test, automated auditory brainstem response
      (AABR), on referral rates to specialist audiology services. METHODS: A
      retrospective analysis was performed of all neonatal hearing screening in
      Letterkenny General Hospital over 5 years, from January 2008 to December 2012,
      which was confined to infants possessing one or more known risk factors for
      permanent childhood hearing impairment. 1,163 infants were screened using AABR
      during this period and subsequent re-test and referral rates to specialist
      audiology services were examined. RESULTS: Of the infants screened, 50 (4.3 %)
      failed the initial AABR. A further 16 of these (32 %) failed the repeat AABR,
      resulting in an overall referral rate to specialist audiology services of 1.38 %.
      CONCLUSION: Our results demonstrate strikingly low overall referral rates in this
      cohort, falling well below both the international benchmark and the initial
      results of the Irish UNHS programme. This provides a convincing argument for
      examining AABR as a potential alternative to TEOAE in the nationwide UNHS.

PMID- 24097064
TI  - Common variants associated with plasma triglycerides and risk for coronary artery
      disease.
AB  - Triglycerides are transported in plasma by specific triglyceride-rich
      lipoproteins; in epidemiological studies, increased triglyceride levels correlate
      with higher risk for coronary artery disease (CAD). However, it is unclear
      whether this association reflects causal processes. We used 185 common variants
      recently mapped for plasma lipids (P < 5 * 10(-8) for each) to examine the role
      of triglycerides in risk for CAD. First, we highlight loci associated with both
      low-density lipoprotein cholesterol (LDL-C) and triglyceride levels, and we show
      that the direction and magnitude of the associations with both traits are factors
      in determining CAD risk. Second, we consider loci with only a strong association
      with triglycerides and show that these loci are also associated with CAD.
      Finally, in a model accounting for effects on LDL-C and/or high-density
      lipoprotein cholesterol (HDL-C) levels, the strength of a polymorphism's effect
      on triglyceride levels is correlated with the magnitude of its effect on CAD
      risk. These results suggest that triglyceride-rich lipoproteins causally
      influence risk for CAD. 

PMID- 24097066
TI  - A genome-wide association study in Han Chinese identifies a susceptibility locus
      for primary Sjogren's syndrome at 7q11.23.
AB  - Primary Sjogren's syndrome is one of the most common autoimmune diseases. So far,
      genetic studies of Sjogren's syndrome have relied mostly on candidate gene
      approaches. To identify new genetic susceptibility loci for primary Sjogren's
      syndrome, we performed a three-stage genome-wide association study in Han
      Chinese. In the discovery stage, we analyzed 556,134 autosomal SNPs in 542 cases
      and 1,050 controls. We then validated promising associations in 2 replication
      stages comprising 1,303 cases and 2,727 controls. The combined analysis
      identified GTF2I at 7q11.23 (rs117026326: Pcombined = 1.31 * 10(-53), combined
      odds ratio (ORcombined) = 2.20) as a new susceptibility locus for primary
      Sjogren's syndrome. Our analysis also confirmed previously reported associations
      in Europeans in the regions of STAT4, TNFAIP3 and the major histocompatibility
      complex (MHC). Fine mapping of the region around GTF2I showed that rs117026326 in
      GTF2I had the most significant association, with associated SNPs extending from
      GTF2I to GTF2IRD1-GTF2I.

PMID- 24097065
TI  - Assessing the phenotypic effects in the general population of rare variants in
      genes for a dominant Mendelian form of diabetes.
AB  - Genome sequencing can identify individuals in the general population who harbor
      rare coding variants in genes for Mendelian disorders and who may consequently
      have increased disease risk. Previous studies of rare variants in phenotypically
      extreme individuals display ascertainment bias and may demonstrate inflated
      effect-size estimates. We sequenced seven genes for maturity-onset diabetes of
      the young (MODY) in well-phenotyped population samples (n = 4,003). We filtered
      rare variants according to two prediction criteria for disease-causing mutations:
      reported previously in MODY or satisfying stringent de novo thresholds (rare,
      conserved and protein damaging). Approximately 1.5% and 0.5% of randomly selected
      individuals from the Framingham and Jackson Heart Studies, respectively, carry
      variants from these two classes. However, the vast majority of carriers remain
      euglycemic through middle age. Accurate estimates of variant effect sizes from
      population-based sequencing are needed to avoid falsely predicting a substantial
      fraction of individuals as being at risk for MODY or other Mendelian diseases.

PMID- 24097069
TI  - Prevalence of skin tears in a long-term care facility.
AB  - PURPOSE: The purpose of this study was to collect baseline data of the prevalence
      of skin tears in a Canadian long-term care (LTC) facility. SUBJECTS AND SETTING:
      The research setting was a 114-bed long-term care facility located in Eastern
      Ontario, Canada. The sample population comprised 113 residents from the facility.
      DESIGN: A cross-sectional, quantitative study design was used to gather baseline
      data on the prevalence of skin tears in the Canadian population living in LTC.
      METHODS: Residents were assessed for presence of skin tears, the number of skin
      tears, and location. Skin tears were categorized according to the validated Payne
      Martin Classification system. Data were collected using a predetermined data
      collection sheet developed for this study. A certified enterostomal therapy nurse
      with previous experience with the assessment of skin tears collected the data
      along with 1 nurse employed by the facility. Data were collected on a single day
      over a 6-hour period. RESULTS: Twenty-five of the 113 participating residents in
      the LTC facility had skin tears, yielding a prevalence of 22%. Category I
      accounted for 51% of skin tears, 16% were category II, and 33% were category III.
      Individuals who were found to have more than 1 skin tear had at least 1 category
      III skin tear. The most common anatomical locations were arms (48%), lower legs
      (40%), and hands (12%). Possible etiologic factors included blunt trauma such as
      banging into objects (44%), trauma associated with activities of daily living
      (20%), and falls (12%); 24% were categorized as idiopathic. CONCLUSION: Study
      findings highlight gaps in our knowledge of skin tears and the need for
      additional studies to more clearly define their epidemiology.

PMID- 24097067
TI  - Variants at multiple loci implicated in both innate and adaptive immune responses
      are associated with Sjogren's syndrome.
AB  - Sjogren's syndrome is a common autoimmune disease (affecting ~0.7% of European
      Americans) that typically presents as keratoconjunctivitis sicca and xerostomia.
      Here we report results of a large-scale association study of Sjogren's syndrome.
      In addition to strong association within the human leukocyte antigen (HLA) region
      at 6p21 (Pmeta = 7.65 * 10(-114)), we establish associations with IRF5-TNPO3
      (Pmeta = 2.73 * 10(-19)), STAT4 (Pmeta = 6.80 * 10(-15)), IL12A (Pmeta = 1.17 *
      10(-10)), FAM167A-BLK (Pmeta = 4.97 * 10(-10)), DDX6-CXCR5 (Pmeta = 1.10 * 10(
      8)) and TNIP1 (Pmeta = 3.30 * 10(-8)). We also observed suggestive associations
      (Pmeta < 5 * 10(-5)) with variants in 29 other regions, including TNFAIP3, PTTG1,
      PRDM1, DGKQ, FCGR2A, IRAK1BP1, ITSN2 and PHIP, among others. These results
      highlight the importance of genes that are involved in both innate and adaptive
      immunity in Sjogren's syndrome.

PMID- 24097070
TI  - In situ visualization and detection of protein sulfenylation responses in living
      cells through a dimedone-based fluorescent probe.
AB  - Sulfenylation is one of the reversible post-translational modifications, playing
      significant roles in cellular redox homeostasis and signaling systems. Herein,
      small fluorescent probe (CPD and CPDDM) based live-cell labelling technology for
      the visualization of protein sulfenylation responses in living cells has been
      developed. This approach enables the detection of protein sulfenylation without
      the need for cell lysis, fixation or purification, and permits the noninvasive
      study of protein sulfenylation in live cells through the direct fluorescent
      readout. This technology also can realize dynamic tracking of protein
      sulfenylation in situ with minimal perturbation to sulfenylated proteins and less
      interference with cellular function. Information on the global distribution and
      dynamic changes of endogenous protein sulfenylation has been obtained.

PMID- 24097072
TI  - Developing a sustainable health and care system: lessons for research and policy.

PMID- 24097074
TI  - Myth: High patient satisfaction means high-quality care.

PMID- 24097071
TI  - Functions and regulation of MUC13 mucin in colon cancer cells.
AB  - BACKGROUND: MUC13 is overexpressed and aberrantly localized in colon cancer
      tissue; however, the specific functions and regulation of MUC13 expression are
      unknown. METHODS: Stable cell lines with either overexpressed or suppressed MUC13
      levels were analyzed to determine cell growth, colony formation, cell migration,
      and cell invasion assays. The molecular mechanisms involved in MUC13 regulation
      were elucidated via chromatin immunoprecipitation (ChIP) and analysis of
      interleukin 6 (IL6) treatments. Colon cancer tissues were analyzed by
      immunohistochemistry (IHC) for the protein levels of MUC13 and P-STAT5 in colon
      cancer cells. RESULTS: Overexpression of MUC13 increased cell growth, colony
      formation, cell migration, and invasion. In concordance, MUC13 silencing
      decreased these tumorigenic features. Overexpression of MUC13 also modulated
      various cancer-associated proteins, including telomerase reverse transcriptase,
      sonic hedgehog, B cell lymphoma murine like site 1, and GATA like transcription
      factor 1. Additionally, MUC13-overexpressing cells showed increased HER2 and P
      ERK expression. ChIP analysis revealed binding of STAT5 to the predicted MUC13
      promoter. IL6 treatment of colon cancer cells increased the expression of MUC13
      via activation of the JAK2/STAT5 signaling pathway. Suppression of JAK2 and STAT5
      signaling by chemical inhibitors abolished IL6-induced MUC13 expression. IHC
      analysis showed increased expression of both P-STAT5 and MUC13 in colon cancer as
      compared to adjacent normal tissue. CONCLUSIONS: The results of this study, for
      the first time, suggest functional roles of MUC13 in colon cancer progression and
      provide information regarding the regulation of MUC13 expression via JAK2/STAT5
      which may reveal promising therapeutic approaches for colon cancer treatment.

PMID- 24097075
TI  - Trapping of interstitial defects: filling the gap between the experimental
      measurements and DFT calculations.
AB  - We show that any impurity will slow the diffusion of oxygen in Nb. Using a first
      principles plane-wave pseudopotential method and the supercell model, we
      calculated the interaction energies between substitutional atoms (SA) (X = Ti, V,
      Ta, Zr, and Hf) and interstitial oxygen in a Nb matrix. All impurities act as
      traps for oxygen: undersized SA (Ti and V) have strongest binding at the nearest
      octahedral interstice, while for oversized SA (Zr and Hf), the strongest trapping
      site is the second-nearest octahedral interstice. We evaluated the diffusion
      coefficients of O in the Nb-X alloys using kinetic Monte Carlo (KMC) modeling
      based in the transition state theory, using our calculated oxygen migration
      energies. From this, the effective (average) X-O interaction energies were
      extracted using the Oriani model (Oriani 1970 Acta Metall. 18 147-57). The
      effective X-O interaction energies are close to the strongest interaction
      energies between X and O obtained from the direct supercell calculations. The
      phenomenological effective diffusion barrier obtained from the KMC modeling is
      close to the energy difference between the most stable configuration and the
      highest saddle point along the diffusion path. Both results demonstrate that the
      weaker trapping site has negligible influence on the diffusion of O.

PMID- 24097076
TI  - Re: Siegrist J, Dragano N, Nyberg ST et al. validating abbreviated measures of
      effort-reward imbalance at work in European cohort studies: the IPD-Work
      consortium.

PMID- 24097077
TI  - Response: letter to the editor of IAOEH by BonKyoo Choi et al. (10.1007/s00420
      013-0908-3).

PMID- 24097078
TI  - A new computer-based Farnsworth Munsell 100-hue test for evaluation of color
      vision.
AB  - To evaluate a computer-based Farnsworth-Munsell (FM) 100-hue test and compare it
      with a manual FM 100-hue test in normal and congenital color-deficient
      individuals. Fifty color defective subjects and 200 normal subjects with a best
      corrected visual acuity >= 6/12 were compared using a standard manual FM 100-hue
      test and a computer-based FM 100-hue test under standard operating conditions as
      recommended by the manufacturer after initial trial testing. Parameters evaluated
      were total error scores (TES), type of defect and testing time. Pearson's
      correlation coefficient was used to determine the relationship between the test
      scores. Cohen's kappa was used to assess agreement of color defect classification
      between the two tests. A receiver operating characteristic curve was used to
      determine the optimal cut-off score for the computer-based FM 100-hue test. The
      mean time was 16 +/- 1.5 (range 6-20) min for the manual FM 100-hue test and 7.4
      +/- 1.4 (range 5-13) min for the computer-based FM 100-hue test, thus reducing
      testing time to <50 % (p < 0.05). For grading color discrimination, Pearson's
      correlation coefficient for TES between the two tests was 0.91 (p < 0.001). For
      color defect classification, Cohen's agreement coefficient was 0.98 (p < 0.01).
      The computer-based FM 100-hue is an effective and rapid method for detecting,
      classifying and grading color vision anomalies.

PMID- 24097079
TI  - Macrophages lift off surface-bound bacteria using a filopodium-lamellipodium hook
      and-shovel mechanism.
AB  - To clear pathogens from host tissues or biomaterial surfaces, phagocytes have to
      break the adhesive bacteria-substrate interactions. Here we analysed the
      mechanobiological process that enables macrophages to lift-off and phagocytose
      surface-bound Escherichia coli (E. coli). In this opsonin-independent process,
      macrophage filopodia hold on to the E. coli fimbriae long enough to induce a
      local protrusion of a lamellipodium. Specific contacts between the macrophage and
      E. coli are formed via the glycoprotein CD48 on filopodia and the adhesin FimH on
      type 1 fimbriae (hook). We show that bacterial detachment from surfaces occurrs
      after a lamellipodium has protruded underneath the bacterium (shovel), thereby
      breaking the multiple bacterium-surface interactions. After lift-off, the
      bacterium is engulfed by a phagocytic cup. Force activated catch bonds enable the
      long-term survival of the filopodium-fimbrium interactions while soluble mannose
      inhibitors and CD48 antibodies suppress the contact formation and thereby inhibit
      subsequent E. coli phagocytosis. 

PMID- 24097080
TI  - Reporting of health-related quality of life (HRQOL) data in oncology trials: a
      comparison of the European Organization for Research and Treatment of Cancer
      Quality of Life (EORTC QLQ-C30) and the Functional Assessment of Cancer Therapy
      General (FACT-G).
AB  - PURPOSE: The inclusion of patient-reported outcome (PRO) instruments to record
      patient health-related quality of life (HRQOL) data has virtually become the norm
      in oncology randomised controlled trials (RCTs). Despite this fact, recent
      concerns have focused on the quality of reporting of HRQOL. The primary aim of
      this study was to evaluate the quality of reporting of HRQOL data from two common
      instruments in oncology RCTs. DESIGN: A meta-review was undertaken of systematic
      reviews reporting HRQOL data collected using PRO instruments in oncology
      randomised controlled trials (RCTs). English language articles published between
      2000 and 2012 were included and evaluated against a methodology checklist.
      RESULTS: Four hundred and thirty-five potential articles were identified. Six
      systematic reviews were included in the analysis. A total of 70,403 patients had
      completed PROs. The European Organization for Research and Treatment of Cancer
      QLQ-C30 and Functional Assessment of Cancer Therapy-General questionnaire
      accounted for 55 % of RCTs. Eighty per cent of RCTs had used psychometrically
      validated instruments; 70 % reported culturally valid instruments and almost all
      reported the assessment timing (96 %). Thirty per cent of RCTS reported clinical
      significance and missing data. In terms of methodological design, only 25 % of
      RCTs could be categorised as probably robust. CONCLUSION: The majority of
      oncology RCTs has shortcomings in terms of reporting HRQOL data when assessed
      against regulatory and methodology guidelines. These limitations will need to be
      addressed if HRQOL data are to be used to successfully support clinical decision
      making, treatment options and labelling claims in oncology.

PMID- 24097068
TI  - Discovery and refinement of loci associated with lipid levels.
AB  - Levels of low-density lipoprotein (LDL) cholesterol, high-density lipoprotein
      (HDL) cholesterol, triglycerides and total cholesterol are heritable, modifiable
      risk factors for coronary artery disease. To identify new loci and refine known
      loci influencing these lipids, we examined 188,577 individuals using genome-wide
      and custom genotyping arrays. We identify and annotate 157 loci associated with
      lipid levels at P < 5 * 10(-8), including 62 loci not previously associated with
      lipid levels in humans. Using dense genotyping in individuals of European, East
      Asian, South Asian and African ancestry, we narrow association signals in 12
      loci. We find that loci associated with blood lipid levels are often associated
      with cardiovascular and metabolic traits, including coronary artery disease, type
      2 diabetes, blood pressure, waist-hip ratio and body mass index. Our results
      demonstrate the value of using genetic data from individuals of diverse ancestry
      and provide insights into the biological mechanisms regulating blood lipids to
      guide future genetic, biological and therapeutic research.

PMID- 24097081
TI  - Thirty years of portraying oral health through models: what have we accomplished
      in oral health-related quality of life research?
AB  - OBJECTIVES: This paper critically examines the different models of oral health
      aimed at representing oral health-related quality of life (OHRQoL) and explores
      the extent to which such models changed conceptually to accommodate current
      theories and empirical knowledge of oral function, impairment and disability.
      METHODS: A critical synthesis of the existing literature based on a comprehensive
      yet non-systematic review using Ovid-MEDLINE was performed. Full text of
      manuscripts available on models of oral health and OHRQoL published in English
      between 1 January 1950 and 30 June 2013 were identified. RESULTS: Nineteen
      manuscripts were identified presenting and discussing various models of oral
      health and OHRQoL that are predominantly negative and linear. These models are
      mostly based on sick role-related theories and do not readily accommodate the
      biopsychosocial theories of oral health. Alternative portrayals have emerged to
      include positive behaviours and adaptive strategies dynamically, but have yet to
      influence patient care and the development of subjective OHRQoL indicators.
      CONCLUSION: Despite the multitude of graphical representations of concepts,
      dental research has remained somewhat 'linear' in portraying the consequences of
      oral diseases as a one-way street. Although the conceptualization of oral health
      has evolved in the past 30 years, dental research still refers to it as the
      absence of disease in more than half a dozen models of OHRQoL focused mostly on
      dysfunction and disability.

PMID- 24097082
TI  - Single center experience with total body irradiation and melphalan (TBI-MEL)
      myeloablative conditioning regimen for allogeneic stem cell transplantation (SCT)
      in patients with refractory hematologic malignancies.
AB  - We retrospectively evaluated the tolerability and efficacy of fractionated total
      body irradiation (TBI) (1,200 cGy) and melphalan (MEL) (100-110 mg/m(2))
      myeloablative conditioning in 48 patients with nonremission AML (n = 14), ALL (n
      = 10), NHL (n = 18), and other refractory hematologic malignancies (n = 6) who
      received allogeneic stem cell transplantation (SCT) between 2002 and 2011. Median
      age was 48 years (22 to 68); 14 out of 26 leukemia patients (54 %) had
      circulating blasts at transplant, 20 (50 %) evaluable patients had poor-risk
      cytogenetics, 12 (25 %) had prior SCT, and 10 (21 %) received stem cells from a
      mismatch donor. All patients received tacrolimus with or without methotrexate for
      GVHD prophylaxis. At the time of analysis, 13 patients (27 %) were alive and
      disease free. Engraftment was complete in all patients. The median time to ANC
      recovery (>500) was 12 days (range, 6-28). The most common grade III and IV
      toxicities were mucositis and infections. Eighteen patients (43 %) developed
      grade II-IV acute GVHD, and eight (26 %) had extensive chronic GVHD. Of 44
      evaluable patients for response, 28 (64 %) achieved a complete remission (CR),
      and seven (15 %) had a partial remission after the transplant. With a median
      follow-up of 30 months (4 to 124 months) for surviving patients, the cumulative
      incidence of relapse was 45 % at 1 year, and the probability of overall survival
      (OS) at 5 years was 22.5 %. Multivariate analysis showed that platelet count
      (<80,000/mL) and lactic dehydrogenase (>500 IU/L) at SCT were associated with
      relapse. Age less than 53 years and CR after SCT were associated with better OS.
      Our data suggest that TBI-MEL can result in CR in two thirds, durable remission
      in one third, and 5-year survival in about one quarter of patients with
      nonremission hematologic malignancies. Further studies with TBI-MEL in standard
      risk transplant patients are warranted.

PMID- 24097083
TI  - High cut-off dialysis as a salvage therapy option in high-dose methotrexate
      chemotherapy?

PMID- 24097084
TI  - Epidemiology of viral respiratory tract infections in an outpatient haematology
      facility.
AB  - Viral respiratory tract infections (VRTI) are an important cause of morbidity and
      mortality in haematology patients, particularly after haematopoietic stem cell
      transplantation (HSCT). The incidence, clinical presentation and outcome of
      symptomatic and asymptomatic VRTI in HSCT outpatient unit were prospectively
      evaluated during a single influenza season (January-March 2011). Pharyngeal swabs
      were performed at the first visit and if new symptoms were present. Molecular
      multiplex assay for 12 respiratory viruses was performed by the regional
      reference laboratory. Among 264 swabs from 193 outpatients, 58 (22 %) resulted
      positive for 61 viruses (influenza, n = 20; respiratory syncytial virus [RSV], n
      = 21; rhinovirus, n = 12; coronavirus, n = 4; adenovirus, n = 3; parainfluenza, n
      = 1). VRTI were detected more frequently in the presence of symptoms than in
      asymptomatic patients: 49 out of 162 (30 %) vs. 9 out of 102 (9 %), p < 0.001.
      Influenza-like illness syndrome (ILI) was significantly associated with a VRTI if
      compared to other presentations (42 %), while the European Centre for Disease
      Prevention and Control definition was not (30 %). Positive predictive value (PPV)
      of ILI for influenza was 17 %. Influenza and RSV peak periods were contemporary.
      Influenza prophylaxis was given to 25 patients following exposure. Low rate of
      progression from upper to lower respiratory tract infection (approximately 5 %
      for influenza and RSV), no nosocomial epidemics and no VRTI-related deaths were
      observed. VRTI are very frequent in high-risk haematology outpatients, but
      symptoms are aspecific and PPV of ILI is low. Symptoms of influenza and RSV
      overlap. Thus, microbiological diagnosis and contact preventive measures are
      crucial. Rather than universal influenza prophylaxis, prompt diagnosis and
      treatment of only documented infections could be pursued.

PMID- 24097085
TI  - Impact of the duration of antiviral prophylaxis on rates of varicella-zoster
      virus reactivation disease in autologous hematopoietic cell transplantation
      recipients.
AB  - Varicella-zoster virus (VZV) reactivation is a relatively common cause of
      morbidity following autologous hematopoietic cell transplant (auto-HCT). The
      Centers for Disease Control in 2009 recommended extending VZV prophylaxis for 1
      year post-transplantation. We retrospectively analyzed rates of VZV reactivation
      following auto-HCT at our transplant center prior to and after the implementation
      of extended antiviral prophylaxis in June 2008. The study population was divided
      into three different cohorts according to the length of VZV prophylaxis as
      following: (1) prophylaxis until neutrophil recovery to >=500/MUL (n = 77), (2)
      prophylaxis for 6 months (n = 12), or (3) 12 months (n = 40) post-auto-HCT. All
      patients received acyclovir 400 mg oral or intravenously twice daily or
      valacyclovir 500 mg oral daily. For patients in whom VZV reactivation occurred,
      data was collected on severity of infection, time of onset, treatment, and any
      associated complications. One hundred twenty-nine patients undergoing auto-HCT
      between January 1, 2004 and January 31, 2010 were included in the study. There
      was a significant difference in the rates of VZV reactivation between the
      neutrophil recovery and 12 months prophylaxis cohorts at 14 % (n = 11) and 2 % (n
      = 1) (P = 0.04), respectively. VZV reactivation rate in the 6-month prophylaxis
      group was 17 % (n = 2), but did not reach statistical significance due to small
      numbers. In the subset of auto-HCT patients treated with bortezomib, 13 % (n = 2)
      developed VZV reactivation in the neutrophil recovery group, while no events
      occurred in the other two cohorts. Complications of VZV reactivation include post
      herpetic neuralgia (n = 5), severe pain (n = 3), scarring (n = 1), and motor
      weakness (n = 1); two patients required hospitalization and three patients
      developed disseminated zoster. Our limited retrospective analysis suggests a
      significant reduction in rates of post-auto-HCT rates of VZV reactivation with
      extended 12 months antiviral prophylaxis. VZV reactivation is a significant
      complication post-auto-HCT, and extended prophylaxis appears to be safe and
      effective in this setting.

PMID- 24097086
TI  - Intracranial pial arteriovenous fistula caused by dural tenting: case report.
AB  - We describe a rare case where a patient developed intracranial pial arteriovenous
      (AV) fistula due to dural tenting. The patient was a 63-year-old woman who had
      undergone neck clipping for an unruptured middle cerebral artery (MCA) aneurysm.
      The surgery was performed without any problems and her postoperative course was
      uneventful. Two weeks after cerebral angiography operation revealed a pial AV
      fistula fed by the right MCA and drained into the vein of Trolard through the
      Sylvian vein which had not existed before surgery. Being diagnosed as de novo
      pial AV fistula, surgical repair was performed. The AV fistula was located just
      beneath the dural tenting. The fistulous point was confirmed with fluorescein
      video angiography and obliterated using a clip. Although rare, we should pay
      attention to the AV fistula due to dural tenting as the complications of cranial
      surgery. 

PMID- 24097087
TI  - Spinal epidural arteriovenous fistulas with unusual manifestation of sudden onset
      of severe neurological deficits: case report.
AB  - Spinal epidural arteriovenous fistulas with perimedullary venous drainage cause
      venous hypertension, and usually manifest as slowly progressive myelopathy. We
      treated two patients presenting with sudden onset of severe neurological
      deficits. Moreover, in Case 1, the venous drainage was exclusively epidural and
      no perimedullary venous drainage was present. Angiographic findings of this
      patient were characterized by a slow-flow fistula with marked retention of the
      epidural venous drainage. Rapidly progressing thrombosis of the epidural venous
      plexus may have caused the sudden onset of the symptoms. In Case 2, hematomyelia
      may also be possibly associated with the sudden onset of the symptoms. Early
      diagnosis and treatment are essential to achieve favorable outcome in such cases
      because venous congestion results in irreversible venous infarction within a
      short period. 

PMID- 24097088
TI  - Simple transposition technique for microvascular decompression using an expanded
      polytetrafluoroethylene "belt": technical note.
AB  - Microvascular decompression (MVD) is a standard surgical procedure for treating
      vascular compression syndromes. There are two basic ways to perform MVD:
      interposition using a prosthesis and transposition. With the transposition
      technique, adhesions and granuloma around the decompression site are avoided, but
      the required operation is more complex than that for the interposition method. We
      describe a simple, quick MVD transposition procedure that uses a small "belt" cut
      from a sheet of 0.3-mm-thick expanded polytetrafluoroethylene membrane. The belt
      has a hole at the wide end and the other end tapered to a point. The belt is
      encircled around offending vessels by inserting the pointed end into the hole.
      The pointed end is then passed through a dural tunnel over the posterior wall of
      the petrous bone and is tied two or three times. This method avoids the risks
      involved in handling a surgical needle close to the cranial nerves and vessels. 

PMID- 24097089
TI  - Posterior fixation for atlantoaxial subluxation in a case with complex anomaly of
      persistent first intersegmental artery and assimilation in the C1 vertebra.
AB  - We report a very rare case of atlantoaxial subluxation (AAS) with persistent
      first intersegmental artery (PFIA) and assimilation in the atlas (C1) vertebra.
      This case demonstrates the difficulty of deciding on a surgical strategy for
      complex anomalies. A 63-year-old man presented with gait disturbance, neck pain,
      and severe dysesthesia in his left arm. Past history included a whiplash injury.
      Dynamic X-ray studies demonstrated an irreducible AAS and assimilation of C1.
      This subluxation was slightly deteriorated in an extended position. A three
      dimensional computed tomography angiography (3DCTA) indicated that the PFIA was
      located on the left side. We performed a C1 posterior arch resection and C1
      lateral mass-axis pedicle screw (C1LM-C2PS) fixation using the modified technique
      of skewering the occipital condyle and C1 lateral mass. The patient had no
      postoperative morbidity and his symptoms disappeared immediately after operation.
      Complex anomalies cause difficulty in determining surgical strategy although
      several surgical methods for simple craniovertebral junction anomaly have been
      reported. To avoid significant morbidities associated with vertebral artery
      injury, surgical strategies for these complex conditions are discussed. The
      modified technique of a C1 lateral mass screw penetrating the occipital condyle
      is a viable treatment option. 

PMID- 24097090
TI  - Isolated superficial sylvian vein thrombosis with long cord sign: case report and
      review of the literature.
AB  - Isolated cortical vein thrombosis (ICVT) is extremely rare. Only single case or
      small series of ICVT have been reported; clinical details are still uncertain. We
      report a case of isolated superficial sylvian vein thrombosis with exceedingly
      long cord sign. A 14-year-old female with severe sudden onset headache visited
      our hospital. Fluid attenuated inversion recovery and echo-planar T2(*)
      susceptibility-weighted imaging (T2(*)SW) showed a long cord sign on the surface
      of the sylvian fissure. The patency of dural sinuses and deep cerebral veins were
      confirmed by magnetic resonance venography (MRV), and diagnosis of ICVT was made.
      She recovered completely without anticoagulant agents. To clarify the clinical
      characteristics of ICVT, we reviewed 51 ICVT cases in the literature. In many
      cases, T2(*)SW was the most useful examination to diagnose ICVT. In contrast with
      general cerebral venous thrombosis, MRV and conventional angiography were either
      supporting or useless. Anastomotic cortical veins were involved frequently;
      symptoms of gyri around the veins were common. It also suggested that ICVTs of
      the silent area might have been overlooked because of nonspecific symptoms, and
      more patients with ICVT may exist. In cases involving patients with nonspecific
      symptoms, the possibility of ICVT should be considered. 

PMID- 24097091
TI  - Unusual traumatic midthoracic spondyloptosis and its surgical management: case
      report.
AB  - Posttraumatic spondyloptosis develops as a result of complete subluxation of the
      vertebral bodies and causes complete transection of the spinal cord. Severe
      trauma-related spondyloptosis of the upper-mid thoracic region is a rare form of
      spinal trauma. Traumatic midthoracic spondyloptosis is quite rare, and radiology
      plays an important role in the diagnosis and treatment of this condition.
      Surgical reconstruction and stabilization are required for early mobilization and
      rehabilitation of patients with this injury. Here, we report the clinical
      features, radiographic findings, and management of an unusual case of traumatic
      midthoracic spondyloptosis that showed complete spinal cord transection and was
      operated. 

PMID- 24097092
TI  - Advantage of microscope integrated for both indocyanine green and fluorescein
      videoangiography on aneurysmal surgery: case report.
AB  - Neck clipping of a large middle cerebral artery aneurysm was performed using a
      newly developed surgical microscope integrated with modules for both indocyanine
      green (ICG) and fluorescein videoangiography. During surgery, ICG and fluorescein
      videoangiography by intra-arterial or intravenous injection were safely carried
      out without interrupting the surgical procedure. Based on the findings obtained
      from the case, we evaluated the differences between the dyes and the injection
      routes. With intra-arterial injection, fluorescein offered sharper contrast
      images and was better at depicting fine arteries than ICG. Patchy staining of
      vessel walls was observed in intravenous fluorescein videoangiography, while it
      was not evident in ICG. Intra-arterial injection method had a great advantage in
      the rapid clearance of the dyes, which allowed us to perform repeated
      videoangiography within a short period, and was useful in detecting incomplete
      clipping in this case; however, catheter insertion requires additional work and
      carries a potential risk. Use of a microscope integrated for both ICG and
      fluorescein videoangiography would be another method for repeated evaluation.
      Namely, alternate use of the dyes enables us to perform videoangiography in a
      short time even via intravenous injection. 

PMID- 24097093
TI  - Intracranial stenting using a drug-eluting stent for moyamoya disease involving
      supraclinoid ICA: a case report.
AB  - A 43-year-old woman was diagnosed with moyamoya disease (MMD) and underwent right
      side bypass surgery. After surgery, previous symptoms disappeared. One month
      later, transient right hemiparetic attacks and motor dysphasia developed.
      Angiography revealed progressive severe stenosis of left supraclinoid segment of
      internal carotid artery. Angioplasty using a drug-eluting stent (DES) was
      performed. For 18 months, she presented no ischemic symptom and no instent
      stenosis was observed in follow-up angiography. This is the first case report
      about effect of DES use for MMD. Considering that intimal hyperplasia is a
      pathophysiology of stenosis, DES may have a role in reducing progression of
      stenosis in selected moyamoya patients. 

PMID- 24097094
TI  - Cauda equina intradural extramedullary cavernous haemangioma: case report and
      review of the literature.
AB  - Cavernous haemangioma (cavernoma) is a benign vascular lesion, exceptionally
      located in cauda equina. We report a case, diagnosed and operated in the
      Department of Neurosurgery from Pitesti County Emergency Hospital, of a 60-year
      old woman with history of lumbar region distress, who presented with low back
      pain, paravertebral muscle contracture, and bilateral lumbar radiculopathy, with
      sudden onset after lifting effort. The preoperative diagnosis was done using
      computed tomography (CT) and magnetic resonance imaging (MRI), and the patient
      underwent surgery-two level laminectomy, dural incision, and tumor dissection
      from the cauda equina nerve roots under operatory microscope. Histopathological
      examination confirmed the positive diagnosis of cavernoma of cauda equina. The
      patient's outcome was favorable, without postoperative neurological deficits. 

PMID- 24097095
TI  - Novel method for analyzing locomotor ability after spinal cord injury in rats:
      technical note.
AB  - In the research for the treatment of spinal cord injury (SCI), the evaluation of
      motor function in model rats must be as objective, noninvasive, and ethical as
      possible. The maximum speed and acceleration of a mouse measured using a SCANET
      system were previously reported to vary significantly according to severity of
      SCI. In the present study, the motor performance of SCI model rats was examined
      with SCANET and assessed for Basso-Beattie-Bresnahan (BBB) score to determine the
      usefulness of the SCANET system in evaluating functional recovery after SCI.
      Maximum speed and acceleration within the measurement period correlated
      significantly with BBB scores. Furthermore, among several phased kinematic
      factors used in BBB scores, the capability of "plantar stepping" was associated
      with a drastic increase in maximum speed and acceleration after SCI. Therefore,
      evaluation of maximum speed and acceleration using a SCANET system is a useful
      method for rat models of SCI and can complement open field scoring scales. 

PMID- 24097096
TI  - C2 nerve root resection to achieve safe and wide exposure of lateral atlantoaxial
      joints in posterior C1-2 instrumented fixation: technical note.
AB  - Posterior atlantoaxial (C1-2) fixation with individual screw placement in C1 and
      C2 has been one of the technical options to treat C1-2 subluxation or
      instability. In the present study, we demonstrate the surgical technique of C2
      nerve root resection to avoid the troublesome bleeding from the perivertebral
      venous plexus and achieve full exposure of the lateral C1-2 joints. The present
      study includes a series of 16 consecutive patients who underwent posterior C1-2
      instrumented fixation with individual screw placement in C1 and C2. All patients
      underwent unilateral or bilateral C2 nerve root resection at the sensory
      ganglion. Screw malposition resulting in vascular or neural injury was not
      encountered. Sensory pain scale analysis indicated that the mean score before
      surgery was 2.4, which significantly improved to 1.4 after surgery. No patients
      reported allodynia or C2 distribution neuropathic pain during the follow-up. C2
      nerve root resection resulted in early postoperative dysesthesia in all 16
      patients; however, neurological examination during the follow-up revealed that
      only 12.5% of all analyzed patients did not demonstrate satisfactory recovery of
      C2 sensory disturbance. Postoperative radiologic analysis revealed solid osseous
      or partial fusion at the lateral C1-2 joints in all cases during the follow-up.
      No case demonstrated non-union with pseudoarthrosis. Although C2 nerve root
      resection is still under debate and not fully justified, the present study
      suggests that C2 nerve root resection does not always result in significant
      morbidity and can be an option for surgical resolution to achieve safe and wide
      exposure of lateral C1-2 joints. 

PMID- 24097097
TI  - An operating microscope with higher magnification and higher resolution for
      cerebral aneurysm surgery: preliminary experience-technical note.
AB  - We describe a higher magnifying power operating microscope system to improve one
      method of high-quality microsurgical clipping for cerebral aneurysm in some
      cases. This higher magnification is achieved by a new lens design in the optical
      system, which makes the image of the object very clear at high magnifications
      (distinctiveness of 7 MUm). This higher-resolution operating microscope system
      provides the surgeon with higher-magnified images (at the maximum of more than
      30* magnifications as each working distance) in the operating field. The
      magnifications can be changed from low power (2.9*) to high power (62.0*)
      depending on the circumstances in a given procedure. We have used this operating
      microscope system on 11 patients with microsurgical clipping for cerebral
      aneurysms. Microsurgical treatment could be performed safely and precisely. All
      aneurysms were treated without any technical complications. We think that the use
      of this microscope would have potential benefits for microsurgical treatment for
      cerebral aneurysms because of better visualization. 

PMID- 24097098
TI  - Effect of medical education on students' attitudes toward psychiatry and
      individuals with mental disorders.
AB  - OBJECTIVE: This study aimed to explore the effect of medical education on
      students' attitudes toward psychiatry and psychiatric patients, and examined the
      usefulness of a new evaluation tool: the 6-item Psychiatric Experience,
      Attitudes, and Knowledge (PEAK-6). METHOD: Authors studied the attitudes of 116
      medical students toward psychiatry and individuals with mental disorders, using
      two questionnaires before and after a 12-week module of "psychosocial medicine."
      Results of the 30-item questionnaire Attitudes Toward Psychiatry (ATP-30) were
      compared with the results of PEAK-6. RESULTS: With the ATP-30, no change in
      attitudes toward psychiatry was observed at the end of the module. With the PEAK
      6, the item "attitude toward psychiatry" significantly improved. Knowledge of and
      experience with psychiatry as well as knowledge of and experience with
      individuals with mental disorders improved significantly; however, attitudes
      toward individuals with mental disorders did not improve. CONCLUSION: PEAK-6
      seems to be a promising tool with regard to nuanced information about psychiatric
      learning experiences. Participation in a psychiatric module may be associated
      with a positive effect on students' knowledge about, experience with, and
      attitudes toward psychiatry, but not attitudes toward psychiatric patients.

PMID- 24097100
TI  - Enhanced electrochemical performance of MWNT@MnO2 composites in polymerized ionic
      liquids.
AB  - In this article, we report a newly devised composite electrode for
      electrochemical capacitors, by depositing manganese dioxide (MnO2) on the surface
      of carbon nanotubes via a spontaneous redox reaction. X-ray diffraction and
      transmission electron microscopic studies demonstrated a homogeneous coating of
      layered MnO2 on the surface of the carbon nanotubes. The MWNT@MnO2 composite
      electrode displayed enhanced capacity performance and rate capability as compared
      to the MnO2 electrode. Introduction of a thin layer of polymerized ionic liquid
      on the surface of the composite electrode enhanced the utilization rate of MnO2
      and improved the conductivity of the resultant electrode. Electrochemical tests
      confirmed the augmented capacity performance and rate capabilities of the polyion
      coated composite electrode. 

PMID- 24097099
TI  - Discrepancy between optic disc and nerve fiber layer assessment and optical
      coherence tomography in detecting glaucomatous progression.
AB  - PURPOSE: To compare the outcomes of Cirrus spectral-domain optical coherence
      tomography (OCT) and optic disc/retinal nerve fiber layer (RNFL) photographic
      assessment in detecting glaucomatous progression. METHODS: Two-hundred twenty-six
      eyes of 130 glaucoma patients (mean follow-up: 2.5 years) with at least 5 OCT
      examinations were included. Eyes were classified into one of four groups (diffuse
      RNFL defect; localized RNFL defect; no RNFL defect; unidentifiable RNFL status)
      based on baseline RNFL photographs. After performing the entire series of optic
      disc/RNFL photographic assessments, the eyes were classified into one of three
      groups: stable, progressed, and undetermined. Progression was divided into one of
      four categories (optic disc rim thinning; widening RNFL defect; deepening RNFL
      defect; new disc hemorrhage). OCT progression was determined using guided
      progression analysis (GPA) software. RESULTS: One-hundred thirty-nine eyes had
      diffuse RNFL defects, 34 eyes had localized RNFL defects, 42 eyes had no RNFL
      defects, and 11 eyes had unidentifiable RNFL at baseline. Forty-six eyes showed
      at least one category of progression upon expert assessment of optic disc/RNFL
      photographs, while OCT GPA detected progression in 35 eyes. Among the 34 eyes in
      which progression was observed in photographs only, 15 showed a new disc
      hemorrhage, 12 presented deepening of an RNFL defect, 10 showed optic disc rim
      change, and 6 had widening of an RNFL defect. Among the 23 eyes processed only by
      OCT GPA, 18 had a diffuse RNFL defect at baseline. CONCLUSION: OCT GPA was more
      sensitive in eyes with a diffuse RNFL defect whereas photographic assessment was
      better for detecting optic disc hemorrhage and deepening of an RNFL defect when
      evaluating structural progression.

PMID- 24097101
TI  - The signal transducers Stat1 and Stat3 and their novel target Jmjd3 drive the
      expression of inflammatory genes in microglia.
AB  - Most neurological diseases are associated with chronic inflammation initiated by
      the activation of microglia, which produce cytotoxic and inflammatory factors.
      Signal transducers and activators of transcription (STATs) are potent regulators
      of gene expression but contribution of particular STAT to inflammatory gene
      expression and STAT-dependent transcriptional networks underlying brain
      inflammation need to be identified. In the present study, we investigated the
      genomic distribution of Stat binding sites and the role of Stats in the gene
      expression in lipopolysaccharide (LPS)-activated primary microglial cultures.
      Integration of chromatin immunoprecipitation-promoter microarray data and
      transcriptome data revealed novel Stat-target genes including Jmjd3, Ccl5, Ezr,
      Ifih1, Irf7, Uba7, and Pim1. While knockdown of individual Stat had little effect
      on the expression of tested genes, knockdown of both Stat1 and Stat3 inhibited
      the expression of Jmjd3 and inflammatory genes. Transcriptional regulation of
      Jmjd3 by Stat1 and Stat3 is a novel mechanism crucial for launching inflammatory
      responses in microglia. The effects of Jmjd3 on inflammatory gene expression were
      independent of its H3K27me3 demethylase activity. Forced expression of
      constitutively activated Stat1 and Stat3 induced the expression of Jmjd3,
      inflammation-related genes, and the production of pro-inflammatory cytokines as
      potently as lipopolysacharide. Gene set enrichment and gene function analysis
      revealed categories linked to the inflammatory response in LPS and Stat1C +
      Stat3C groups. We defined upstream pathways that activate STATs in response to
      LPS and demonstrated contribution of Tlr4 and Il-6 and interferon-gamma
      signaling. Our findings define novel direct transcriptional targets of Stat1 and
      Stat3 and highlight their contribution to inflammatory gene expression. KEY
      MESSAGE: Combined analysis of genomic Stat occupancy and transcriptome revealed
      novel Stat target genes in LPS-induced microglia. Jmjd3 transcription factor is a
      novel transcriptional target of Stat1 and Stat3. Stat1 and Stat3 cooperate with
      Jmjd3 to induce the expression of pro-inflammatory genes. Constitutively active
      Stat1 and Stat3 fully mimic the LPS-induced upregulation of inflammatory genes
      and secretion of cytokines.

PMID- 24097102
TI  - Cytomegalovirus and brain tumor: epidemiology, biology and therapeutic aspects.
AB  - PURPOSE OF REVIEW: First described in 2002, the presence and role of human
      cytomegalovirus (HCMV) infection in glioblastoma (GBM) has remained a
      controversial topic. New research indicates HCMV gene products likely promote GBM
      pathogenesis and that therapies aimed at HCMV might influence disease
      progression. RECENT FINDINGS: Recently, investigators have begun to analyze HCMV
      genome and proteins present in GBM cells in vivo. Furthermore, the research has
      demonstrated that several HCMV gene products that have oncomodulatory properties
      are expressed in GBM and may be impacting tumor pathogenesis in vivo. These HCMV
      gene products modulate GBM proliferation, apoptosis, angiogenesis, invasion and
      immune evasion. A recent mouse model provides mechanistic information as to how
      CMV may promote gliomagenesis in the setting of tumor suppressor dysfunction and
      STAT3 signaling. In addition, clinical outcomes of GBM patients are associated
      with the degree of HCMV infection. Novel therapies aimed at direct antiviral and
      immunotherapy approaches to HCMV suggest that these modalities may impact the
      future treatment of this disease. SUMMARY: A more precise understanding of the
      role of HCMV infection in gliomagenesis and GBM pathogenesis could reveal novel
      therapeutic and preventive strategies.

PMID- 24097103
TI  - Personalized medicine for metastatic breast cancer.
AB  - PURPOSE OF REVIEW: With recent advances in DNA sequencing technology, recurrent
      genomic alterations can be identified in tumor samples from patients with
      metastatic breast cancer (MBC) to enrich clinical trials testing targeted
      therapies. This review provides an overview of clinically relevant genomic
      alterations in MBC and summarizes the recent clinical data from early phase
      trials of novel targeted treatments. RECENT FINDINGS: The clinical development of
      personalized treatment includes targeted agents directed against PI3K/mTOR,
      fibroblast growth factor receptor (FGFR), human epidermal growth factor receptor
      2 (HER2), DNA repair, and cell cycle pathways. PI3K/mTOR pathway drugs are active
      in endocrine and trastuzumab-resistant disease. Drugs targeted at PI3K/mTOR,
      FGFR, and poly(ADP-ribose) polymerase show early signs of efficacy in MBC
      subpopulations enriched with relevant pathway aberrancies. Regimens combining
      targeted agents with either endocrine, anti-HER2, or chemotherapy treatments are
      also being studied in hormone receptor-defined and HER2-defined or pathway
      enriched subgroups. SUMMARY: A new approach to personalized medicine for MBC that
      involves molecular screening for clinically relevant genomic alterations and
      genotype-targeted treatments is emerging. Clinical trials are needed to determine
      whether rare subpopulations of MBC benefit from genotype-targeted treatments.

PMID- 24097104
TI  - Putting poly (ADP-ribose) polymerase and other DNA repair inhibitors into
      clinical practice.
AB  - PURPOSE OF REVIEW: Poly (ADP-ribose) polymerase (PARP) and other DNA repair
      inhibitors are currently tested in numerous clinical trials, with variable
      success. Inhibitors are used in monotherapy, for example, PARP inhibitors in BRCA
      mutated cancers, or more widely in combination treatments. DNA repair inhibitors
      have, as chemotherapy, great potential for long-term disease control, or
      potentially even cures. However, the design of clinical trials using DNA repair
      inhibitors is intricate, as these inhibitors may also potentiate normal tissue
      toxicity without improving overall disease control. RECENT FINDINGS: Recent
      findings of mechanism of action of PARP inhibitors and other DNA repair
      inhibitors are presented, and how the underlying genetic background and interplay
      between DNA repair pathways influence the choice of tumour location and
      combination strategies. The hallmark of individualized cancer therapy is to be
      able to genetically distinguish the responding subclass of cancer patients, and
      it is widely used when targeting oncogenes. The PARP inhibitors in BRCA mutated
      cancers also demonstrate that this approach is possible in a synthetic lethal
      context. SUMMARY: There is strong proof-of-concept for DNA repair inhibitors
      being a useful anticancer strategy in well designed clinical trials.

PMID- 24097105
TI  - Targeted therapy with monoclonal antibodies in acute lymphoblastic leukemia.
AB  - PURPOSE OF REVIEW: To describe the current new targeted therapy with monoclonal
      and bispecific antibodies in adult acute lymphoblastic leukemia (ALL), to improve
      response rates and outcome. RECENT FINDINGS: Blast cells in ALL express a variety
      of specific antigens, such as CD19, CD20, CD22, CD33 and CD52, and recently
      monoclonal antibodies (MoAbs) became available to target these antigens. The anti
      CD20 MoAb rituximab has substantially improved the outcome in Burkitt
      lymphoma/leukemia, and is currently applied in de-novo B-precursor ALL. The MoAbs
      directed against CD22, linked to cytotoxic agents, either to calicheamicin
      (inotuzomab ozogamicin) or to plant or bacterial toxins (epratuzumab) are
      explored in refractory/relapsed childhood and adult ALL. Targeting CD19 is of
      great interest, as it is expressed in all B-lineage cells, including early
      precursors. The new bispecific antibody blinatumomab combines single chain
      antibodies to CD19 and CD3, and thereby T cells lyse the CD19 bearing B cells and
      is effective in patients with positive minimal residual disease (MRD) or
      refractory/relapsed ALL. SUMMARY: Antibody therapy in ALL is very promising, with
      high rate of complete remission and MRD-negativity in advanced ALL. It is
      currently explored in de-novo ALL to establish the best setting in combination
      with chemotherapy or even as a monotherapy.

PMID- 24097106
TI  - Molecular biomarkers in pediatric glial tumors: a needed wind of change.
AB  - PURPOSE OF REVIEW: Glial tumors of the central nervous system (CNS) are the
      leading cause of cancer-related death and morbidity in children. Their
      diagnosis/prognosis relies mainly on clinical and histopathological factors.
      However, pathological grading is particularly challenging as there is substantial
      molecular heterogeneity in pediatric CNS tumors, which results in variable
      biological behavior in tumors with potentially identical histological diagnoses
      or limited reliable measures of classification for given subgroups. Novel
      molecular markers/pathways identified by integrated
      genomic/transcriptomic/epigenomic studies of cohorts of pediatric gliomas are
      revolutionizing this field and are summarized herein. RECENT FINDINGS: Studies of
      pediatric gliomas have identified unexpected oncogenic pathways implicated in
      gliomagenesis. These range from a single pathway/molecule defect such as
      abnormalities of the mitogen-activated-protein-kinase pathway considered to be a
      hallmark of pilocytic astrocytomas, to alterations in epigenomic modulators in
      higher-grade tumors. Importantly, the type, timing, and spatial clustering of
      these molecular alterations provide a better understanding of the pathogenesis of
      gliomas and critical markers for therapy that will help refine pathological
      grading. SUMMARY: Reappraisal of glioma classification using these novel
      biomarkers will likely change practice toward molecular pathology and their
      integration into clinical trials will enable personalized therapies based on the
      molecular fingerprint of individual tumors.

PMID- 24097107
TI  - Update on current and potential nanoparticle cancer therapies.
AB  - PURPOSE OF REVIEW: To summarize the most recent preclinical and clinical
      advancements in therapeutic nano-oncology. RECENT FINDINGS: First-generation
      nanotherapies are well tolerated in humans and evidence shows that they are
      efficacious, while at the same time reducing the burden of side-effects. Most of
      these therapies are not specifically targeted, but take advantage of enhanced
      passive accumulation within tumors to preferentially deliver chemotherapies that
      demonstrate off-target toxicities when administered as free drugs. Also, actively
      targeted nanotherapies are entering the clinical arena and preliminary data are
      encouraging. Finally, a number of exciting preclinical developments in
      nanotechnology provide clear evidence that nanotherapies will continue to enter
      the clinic and will have a significant impact in oncology. SUMMARY: A number of
      intriguing nanoparticle therapies are being tested in preclinical and clinical
      trials. Nanoparticles with increasing molecular sophistication, specific
      targeting properties, and unique mechanisms of action will find their way to the
      clinic. Certainly, nanoparticle-based therapies will be increasingly represented
      in drug development pipelines, and will continue to provide efficacious and well
      tolerated drug options for patients with cancer.

PMID- 24097108
TI  - New strategies to overcome resistance to mammalian target of rapamycin inhibitors
      in breast cancer.
AB  - PURPOSE OF REVIEW: To review the studies addressing mammalian target of rapamycin
      (mTOR) inhibitors in breast cancer and resistance to rapalogs. Preclinical and
      clinical studies have suggested mTOR inhibitors may help overcome the resistance
      to endocrine therapy and trastuzumab. Despite much interest, knowledge of the
      mechanism and molecular response to mTOR inhibitors is incomplete. RECENT
      FINDINGS: Resistance to mTOR inhibitors has been explored in preclinical studies
      and can be defined as primary, associated with amplifications or mutations of
      different kinases, or secondary, in which rapalog activates the feedback loops
      involving the insulin-like growth factor I receptor (IGF-IR), platelet-derived
      growth factor receptor and mitogen-activated protein kinase (MAPK) pathway.
      Current clinical trials are testing the combinations of rapamycin with other
      kinase inhibitors including IGF-IR, phosphoinositide 3-kinase and MAPK
      extracellular signal-regulated kinase inhibitors. SUMMARY: Recent findings on the
      resistance to rapalogs have stimulated the assessment of combinations of
      inhibitors in clinical trials. This review summarizes the current knowledge of
      primary and secondary rapalog resistance, and the current efforts to overcome
      this resistance.

PMID- 24097109
TI  - Issues in clinical research for metastatic breast cancer.
AB  - PURPOSE OF REVIEW: Technical advances and progresses in tumor biology hold
      promise for the advent of new anticancer agents. These changes are impacting the
      conduct and design of clinical trials. This review describes the changing
      landscape of clinical research in metastatic breast cancer (MBC). RECENT
      FINDINGS: Clinical trials in breast cancer that started between 2007 and 2011
      were analyzed. In the metastatic setting, 72% (n = 479) of these studies
      evaluated targeted therapies and 21% (n = 139) conventional treatments. During
      this period, the number of phase II trials decreased over time, whereas biology
      driven studies, although small in terms of absolute number, now represent 15% of
      the total. Nevertheless, genomic segments are too rare to allow conventional drug
      development and require changes in the way clinical trials are being done.
      Several options are being explored to address this challenge: develop large
      consortium, perform molecular screening in larger populations, develop clinical
      trials testing algorithm for treatment decision, and no longer drugs. SUMMARY:
      The landscape of clinical research in MBC is changing with the development of
      molecular medicine. Research institutions and cooperative groups will need to
      adapt to this changing landscape in clinical research.

PMID- 24097110
TI  - Steady-state production of IL-4 modulates immunity in mouse strains and is
      determined by lineage diversity of iNKT cells.
AB  - Invariant natural killer T cells (iNKT cells) can produce copious amounts of
      interleukin 4 (IL-4) early during infection. However, indirect evidence suggests
      they may produce this immunomodulatory cytokine in the steady state. Through
      intracellular staining for transcription factors, we have defined three subsets
      of iNKT cells (NKT1, NKT2 and NKT17) that produced distinct cytokines; these
      represented diverse lineages and not developmental stages, as previously thought.
      These subsets exhibited substantial interstrain variation in numbers. In several
      mouse strains, including BALB/c, NKT2 cells were abundant and were stimulated by
      self ligands to produce IL-4. In those strains, steady-state IL-4 conditioned
      CD8(+) T cells to become 'memory-like', increased serum concentrations of
      immunoglobulin E (IgE) and caused dendritic cells to produce chemokines. Thus,
      iNKT cell-derived IL-4 altered immunological properties under normal steady-state
      conditions. 

PMID- 24097111
TI  - A DNA break- and phosphorylation-dependent positive feedback loop promotes
      immunoglobulin class-switch recombination.
AB  - The ability of activation-induced cytidine deaminase (AID) to efficiently mediate
      class-switch recombination (CSR) is dependent on its phosphorylation at Ser38;
      however, the trigger that induces AID phosphorylation and the mechanism by which
      phosphorylated AID drives CSR have not been elucidated. Here we found that
      phosphorylation of AID at Ser38 was induced by DNA breaks. Conversely, in the
      absence of AID phosphorylation, DNA breaks were not efficiently generated at
      switch (S) regions in the immunoglobulin heavy-chain locus (Igh), consistent with
      a failure of AID to interact with the endonuclease APE1. Additionally, deficiency
      in the DNA-damage sensor ATM impaired the phosphorylation of AID at Ser38 and the
      interaction of AID with APE1. Our results identify a positive feedback loop for
      the amplification of DNA breaks at S regions through the phosphorylation- and ATM
      dependent interaction of AID with APE1. 

PMID- 24097112
TI  - Epidemiology and importance of renal dysfunction in heart failure patients.
AB  - Renal dysfunction (RD) is a frequent comorbid condition and a major determinant
      of outcomes in patients with heart failure (HF). It is likely that the etiology
      of RD in patients with HF is much more complex than we first thought and
      represents a matrix of independent, albeit interacting, pathophysiological
      pathways with effects on both the kidney and the heart that share a common
      denominator: aging and inflammation. Renal dysfunction in HF has been attributed,
      among others, to biochemical, hormonal, and hemodynamic factors, coupled with
      pharmacological interventions. Regardless of the cause, the development of RD or
      worsening renal function is common in patients with HF, and is associated with
      increased morbidity and mortality. There is increasing evidence, however, that
      transient increases in creatinine in the setting of acute HF are not
      prognostically important, whereas persistent deterioration does portend a higher
      mortality in this patient population. In addition, congestion seems to play an
      important role in the course of renal deterioration, and the combination of
      congestion and worsening renal function is the most significant clinical
      prognosticator in HF patients. This review aims to provide an update on the
      epidemiology and prognostic significance of RD in HF patients, in both the acute
      and the chronic setting. 

PMID- 24097113
TI  - Ventricular remodeling in heart failure with preserved ejection fraction.
AB  - Heart failure with preserved ejection fraction (HFpEF) is common, increasing in
      prevalence, and causes substantial morbidity and mortality. HFpEF has commonly
      been viewed as an expression of advanced hypertensive heart disease, with a
      cardiac phenotype characterized by an increase in wall thickness-to-chamber
      radius ratio (concentric hypertrophy). However, marked clinical heterogeneity
      within this syndrome is now well appreciated, and is mirrored in the variability
      in left ventricular (LV) structure. A review of larger imaging studies from
      epidemiology and clinical trial cohorts demonstrate that while concentric LV
      remodeling is common, it is by no means universal and many patients demonstrate
      normal LV geometry or even an eccentric pattern. More detailed assessment of
      cardiac structure and function in broader HFpEF populations will be necessary to
      better define the prevalence, determinants, and prognostic relevance of these
      measures, which may in turn serve as a foundation to identify
      pathophysiologically relevant sub-phenotypes within this diverse syndrome. 

PMID- 24097115
TI  - Superacid synthesized tertiary benzenesulfonamides and benzofuzed sultams act as
      selective hCA IX inhibitors: toward understanding a new mode of inhibition by
      tertiary sulfonamides.
AB  - A series of tertiary (fluorinated) benzenesulfonamides was synthesized in
      superacid HF-SbF5. To circumvent the problem of the in situ iminium ion
      formation, proved by low temperature NMR experiments, a tandem superacid
      catalysed cross-coupling reaction was employed to synthesize the benzofuzed
      sultams analogues. These tertiary benzenesulfonamides were tested as inhibitors
      of human carbonic anhydrases (hCAs, EC 4.2.1.1). These compounds did not inhibit
      the widespread off target hCA II isoform and showed strong selectivity toward
      tumor-associated carbonic anhydrase isoform IX. A dramatic effect of the
      electronic and structural shape of the inhibitors on selectivity was
      demonstrated, confirming the non-zinc-bonding mode of inhibition of this class of
      sulfonamides. This work allowed identifying a highly selective hCA IX inhibitor
      lead in this series. 

PMID- 24097114
TI  - Sleep apnea, heart failure, and pulmonary hypertension.
AB  - Despite the emergence of sleep apnea (SA) as a significant risk factor for heart
      failure (HF) mortality, data indicate that SA remains under-diagnosed and under
      treated. Less well established, though perhaps more emphasized, is the role of
      sleep apnea in pulmonary hypertension (PH). SA occurs in approximately 50 % of HF
      patients, and its consequences include intermittent hypoxemia, arousal, and intra
      thoracic pressure swings leading to neurohormonal stimulation, oxidative stress
      and inflammation. While SA is also considered a cause of PH, severe PH due solely
      to SA is rare. Combining the results of several studies using Swan-Ganz catheters
      for diagnosis of PH, approximately 10 % of patients with OSA have PH. Effective
      treatment of SA in HF is associated with improved survival, while treatment of SA
      in PH is typically associated with modest hemodynamic improvement.

PMID- 24097116
TI  - Spontaneous bilateral corneal perforation in a patient with ichthyosis.
AB  - We present an 8-month-old female patient with bilateral spontaneous corneal
      perforation and lamellar ichthyosis. On examination, the skin of the body and
      face of the patient was completely dry and scaly. Cicatricial ectropion and
      descemetocele with small perforations were seen. Double-layered amniotic membrane
      transplantation on the cornea with eyelid construction was performed on both
      eyes. At the 6-month follow-up, lower eyelid minimal ectropion formation and
      inferior corneal leukoma were seen bilaterally. In ichthyosis patients, the
      cornea should be monitored closely due to the risk of severe visual loss and
      corneal perforation. 

PMID- 24097117
TI  - Reply: 'Central retinal artery occlusion and cerebral stroke'.

PMID- 24097118
TI  - Central retinal artery occlusion and cerebral stroke.

PMID- 24097119
TI  - Scleral fixation of Ahmed glaucoma valve tube tip for adjustment of cornea
      touching malposition.
AB  - PURPOSE: Tube-corneal touch occurring after Ahmed glaucoma valve (AGV)
      implantation is conventionally treated by tube cutting or tube transposition from
      the original pathway. However, in some cases, tube cutting is insufficient, and
      rearranging the pathway of the tube through a new sclera tunnel, ciliary sulcus,
      or pars plana is not feasible, as the conjunctiva and sclera covering the tube
      are difficult to be redissected. So, we propose a novel technique that
      repositions malpositioned AGV tube using scleral fixation and its successful
      applications in two patients with tube-corneal touch. METHODS: (A) A scleral flap
      is made at the point for scleral fixation. (B) The anterior chamber is maintained
      using an anterior chamber maintainer. The incision is made immediately above the
      tube entering the anterior chamber and the tube end is flipped out using a
      Sinskey. (C) A double-armed 10/0 prolene straight needle is penetrated through
      the tube end. The leading needle enters the anterior chamber through the
      previously made incision and is pulled through the scleral flap. (D) The tube tip
      and the second needle of the double-armed 10/0 prolene straight needle also enter
      the anterior chamber through the previously made incision and the second needle
      is pulled through the scleral flap. The tube end is extended to be parallel to
      the cornea surface. RESULTS: Patients maintained good tube positioning without
      any serious complications during average of 15 months of follow-up after
      operation. CONCLUSION: We believe that our method is a simple and minimally
      invasive surgical method for treating AGV tube touching of the corneal
      endothelium. However, considering the limited number of cases studied and the
      short follow-up period, a larger group with a longer follow-up period is
      necessary.

PMID- 24097120
TI  - The incidence of serious eye injury in Scotland: a prospective study.
AB  - PURPOSE: Ocular trauma remains an important cause of visual morbidity worldwide.
      A previous population-based study in Scotland reported a 1-year cumulative
      incidence of 8.14 per 100 000 population. The purpose of this study was to
      identify any change in the incidence and pattern of serious ocular trauma in
      Scotland. METHODS: This study was a 1-year prospective observational study using
      the British Ophthalmological Surveillance Unit reporting scheme among Scottish
      ophthalmologists. Serious ocular trauma was defined as requiring hospital
      admission. Data were collected using two questionnaires for each patient 1 year
      apart. RESULTS: The response rate from ophthalmologists was 77.1%. There were 102
      patients reported with complete data giving an incidence of 1.96 per 100 000
      population, four times less than in 1992. In patients younger than 65 years, the
      age-adjusted incidence ratio (males/females) indicated a ninefold higher risk of
      trauma in males. In 25 patients (27.2%), the injured eye was blind (final visual
      acuities (FVA) <6/60), 24 being attributable to the eye injury. Standardised
      morbidity ratios suggested a threefold decrease in risk of poor visual outcome in
      2009 compared with 1992. CONCLUSIONS: The incidence of serious ocular trauma has
      fallen; this study has shown hospital admission for serious eye injury in
      Scotland has decreased fourfold in 17 years. Young adult males continue to be at
      highest risk, which needs to be specifically addressed in future health
      prevention strategies. This study also observed a reduction in visual loss from
      serious ocular injuries, although the reasons for this require further
      exploration.

PMID- 24097121
TI  - Influence of cataract maturity on aqueous humor lipid peroxidation markers and
      antioxidant enzymes.
AB  - PURPOSE: The impact of cataract maturity on the aqueous humor (AH)
      oxidant/antioxidant balance is largely controversial. This study was aimed at
      assessing the relationships between cataract maturity and AH lipid peroxidation
      markers and enzymatic antioxidants. PATIENTS AND METHODS: The concentrations of
      conjugated dienes (CD), lipofuscin-like fluorescent end-products (LLF), soluble
      proteins, as well as the activities of superoxide dismutase (SOD) and catalase
      (CAT) were measured in AH samples from nondiabetic patients with either immature
      (n=15) or mature (n=15) cataract. RESULTS: In the overall AH sample, the mean
      values of CD, LLF, SOD, and CAT were 0.160 +/- 0.024 (OD234), 166 +/- 27 RFU,
      24.5 +/- 7.1 U/ml, and 31.9 +/- 3.9 pmol/ml, respectively. CD was positively
      correlated with SOD (r=0.647; P<0.001), CAT (r=-0.394; P=0.031), and LLF (r=
      0.399; P=0.029). The LLF was negatively correlated with SOD (r=-0.461; P=0.010).
      In samples adjusted for confounding factors, differences between immature and
      mature cataract groups regarding SOD, CD, LLF, and total proteins were
      significant (P<0.05; for all variables). The multiple logistic regression
      analysis identified LLF (OR=4.08; P=0.038) and SOD (OR=4.99; P=0.031) as
      independent predictors of cataract maturity. CONCLUSIONS: These results suggest
      that AH lipid peroxidation markers and antioxidants may significantly depend on
      the cataract maturity stage.

PMID- 24097123
TI  - Spin-triplet paired state induced by Hund's rule coupling and correlations: a
      fully statistically consistent Gutzwiller approach.
AB  - The intrasite and intersite spin-triplet pairing gaps induced by interband Hund's
      rule coupling and their correlations are analyzed in the doubly degenerate
      Hubbard Hamiltonian. To include the effect of correlations, the statistically
      consistent Gutzwiller approximation is used. In this approach the consistency
      means that the averages calculated from the self-consistent equations and those
      determined variationally coincide with each other. Emphasis is put on the
      solution for which the average particle number is conserved when carrying out the
      Gutzwiller projection. This method leads to a stable equal-spin paired state in
      the so-called repulsive interactions limit (U > 3J) in the regime of moderate
      correlations. The interband hybridization introduces an inequivalence of the
      bands which, above a critical magnitude, suppresses the paired state due to both
      the Fermi-wavevector mismatch for the Cooper pair and the interband hopping
      allowed by the Pauli principle.

PMID- 24097122
TI  - Primary school teachers in China: associations of organizational justice and
      effort-reward imbalance with burnout and intentions to leave the profession in a
      cross-sectional sample.
AB  - OBJECTIVE: We examined associations of organizational justice (OJ) and effort
      reward imbalance (ERI) with burnout and intentions to leave the teaching
      profession (ILTP) among primary school teachers in China. METHODS: Six primary
      schools located in Wuhan, China, were randomly selected from three different
      socioeconomic areas in 2010. In total, these schools employed 533 teachers, and
      436 of these (82 %) participated in a cross-sectional survey. OJ and ERI were
      assessed by 13-item and 10-item questionnaires, respectively. Burnout was
      measured using the emotional exhaustion subscale of the Chinese Maslach Burnout
      Inventory. ILTP were operationalized based on the frequency of thoughts about
      turnover during the past year. Logistic regression-based odds ratios (ORs) with
      95 % confidence intervals (CIs) were estimated separately for OJ and ERI. In a
      second step, these work stress scales were entered into the same regression
      model. RESULTS: Separate regression models suggested moderate to strong
      associations of OJ and ERI with burnout and ILTP. After simultaneous adjustment,
      the overall OJ score remained associated with burnout and ILTP, but ERI appeared
      to be the stronger and more consistent determinant of both outcomes. For
      instance, an increase of 1 standard deviation of the ERI score was associated
      with an OR of 2.60 (95 % CI 1.97-3.43) for burnout and with an OR of 2.26 (95 %
      CI 1.66-3.08) for ILTP. CONCLUSIONS: Organizational justice and in particular ERI
      appeared to be determinants of burnout and ILTP among primary school teachers in
      China.

PMID- 24097124
TI  - Effects of morphine and fentanyl on 5-fluorouracil sensitivity in human colon
      cancer HCT116 cells.
AB  - Opioids are widely used for perioperative pain management in cancer surgery
      patients. It has been reported that opioids may alter cancer recurrence or
      progression; however, there are no published reports regarding the effects of
      opioids on chemotherapy after cancer surgery. Here we investigated the effects of
      opioids (morphine or fentanyl) on cell proliferation and 5-fluorouracil
      sensitivity in the human colon cancer cell line, HCT116. First, we exposed cancer
      cells to the opioid at various concentrations for 6 or 24 h and evaluated cell
      proliferation using a MTT assay. Next, to simulate the potential postoperative
      situation in which anticancer drugs are administered after cancer surgery, cancer
      cells were incubated with the opioid for 6 or 24 h, followed by treatment with 5
      fluorouracil for 48 h. Although fentanyl did not affect cell proliferation,
      morphine exposure for 6 h enhanced the proliferation. However, sensitivity of
      HCT116 cells to 5-fluorouracil was not altered in all treatment groups. The
      current study demonstrated that the opioids commonly used during postoperative
      periods do not affect 5-fluorouracil sensitivity in human colon cancer HCT116
      cells. 

PMID- 24097126
TI  - Ultrafast optical control using the Kerr nonlinearity in hydrogenated amorphous
      silicon microcylindrical resonators.
AB  - Microresonators are ideal systems for probing nonlinear phenomena at low
      thresholds due to their small mode volumes and high quality (Q) factors. As such,
      they have found use both for fundamental studies of light-matter interactions as
      well as for applications in areas ranging from telecommunications to medicine. In
      particular, semiconductor-based resonators with large Kerr nonlinearities have
      great potential for high speed, low power all-optical processing. Here we present
      experiments to characterize the size of the Kerr induced resonance wavelength
      shifting in a hydrogenated amorphous silicon resonator and demonstrate its
      potential for ultrafast all-optical modulation and switching. Large wavelength
      shifts are observed for low pump powers due to the high nonlinearity of the
      amorphous silicon material and the strong mode confinement in the
      microcylindrical resonator. The threshold energy for switching is less than a
      picojoule, representing a significant step towards advantageous low power silicon
      based photonic technologies. 

PMID- 24097125
TI  - The physiological roles of apolipoprotein J/clusterin in metabolic and
      cardiovascular diseases.
AB  - Several isoforms of apolipoprotein J/clusterin (CLU) are encoded from a single
      gene located on chromosome 8 in humans. These isoforms are ubiquitously expressed
      in the tissues, and have been implicated in aging, neurodegenerative disorders,
      cancer progression, and metabolic/cardiovascular diseases including dyslipidemia,
      diabetes, atherosclerosis and myocardial infarction. The conventional secreted
      form of CLU (sCLU) is thought to be a component of high density lipoprotein
      cholesterol. sCLU functions as a chaperone for misfolded proteins and it is
      thought to promote survival by reducing oxidative stress. Nuclear CLU, a
      truncated CLU formed by alternative splicing, is responsible for promoting
      apoptosis via a Bax-dependent pathway. There are putative regulatory sites in the
      promoter regions of CLU, which are occupied by transcription factors such as
      transforming growth factor (TGF)-beta inhibitory element, activator protein-1,
      CLU-specific elements, and carbohydrate response element. However, the molecular
      mechanisms underlying the distinct roles of CLU in a variety of conditions remain
      unclear. Although the function of CLU in cancer or neurological disease has been
      studied intensively for three decades, physiological roles of CLU seem unexplored
      in the cardiovascular system and metabolic diseases. In this review, we will
      discuss general characteristics and regulations of CLU based on previous
      literature and assess the recent findings associated with its physiological roles
      in different tissues including the vasculature, heart, liver, kidney, adipose
      tissue, and brain. 

PMID- 24097127
TI  - Nonclinical toxicology assessments support the chronic safety of dapagliflozin, a
      first-in-class sodium-glucose cotransporter 2 inhibitor.
AB  - Dapagliflozin, a first-in-class, selective inhibitor of sodium-glucose
      cotransporter 2 (SGLT2), promotes urinary glucose excretion to reduce
      hyperglycemia for the treatment of type 2 diabetes. A series of nonclinical
      studies were undertaken to evaluate dapagliflozin in species where it was shown
      to have pharmacologic activity comparable with that in humans at doses that
      resulted in supratherapeutic exposures. In vitro screening (>300 targets; 10
      MUmol/L) indicated no significant off-target activities for dapagliflozin or its
      primary human metabolite. Once daily, orally administered dapagliflozin was
      evaluated in Sprague-Dawley rats (<=6 months) and in beagle dogs (<=1 year) at
      exposures >5000-fold those observed at the maximum recommended human clinical
      dose (MRHD; 10 mg). Anticipated, pharmacologically mediated effects of
      glucosuria, osmotic diuresis, and mild electrolyte loss were observed, but there
      were no adverse effects at clinically relevant exposures, including in the
      kidneys or urogenital tract. The SGLT2-/- mice, which show chronic glucosuria,
      and dapagliflozin-treated, wild-type mice exhibited similar safety profiles. In
      rats but not dogs, dapagliflozin at >2000-fold MRHD exposures resulted in tissue
      mineralization and trabecular bone accretion. Investigative studies suggested
      that the effect was not relevant to human safety, since it was partially related
      to off-target inhibition of SGLT1, which was observed only at high doses of
      dapagliflozin and resulted in intestinal glucose malabsorption and increased
      intestinal calcium absorption. The rigorous assessment of supra- and off-target
      dapagliflozin pharmacology in nonclinical species allowed for a thorough
      evaluation of potential toxicity, providing us with confidence in its safety in
      patients with diabetes. 

PMID- 24097129
TI  - Whiplash after motor vehicle crashes.

PMID- 24097130
TI  - Indian Supreme Court halts approval of new clinical trials until regulatory
      framework is set up.

PMID- 24097128
TI  - Efficacy of anti-inflammatory or antibiotic treatment in patients with non
      complicated acute bronchitis and discoloured sputum: randomised placebo
      controlled trial.
AB  - OBJECTIVE: To evaluate the efficacy of oral anti-inflammatory or antibiotic
      treatment compared with placebo in the resolution of cough in patients with
      uncomplicated acute bronchitis and discoloured sputum. DESIGN: Multicentre,
      parallel, single blinded placebo controlled, randomised clinical trial. SETTING:
      Nine primary care centres in Spain. PARTICIPANTS: Adults aged 18 to 70 presenting
      symptoms associated with respiratory tract infection of less than one week's
      duration, with cough as the predominant symptom, the presence of discoloured
      sputum, and at least one other symptom of lower respiratory tract infection
      (dyspnoea, wheezing, chest discomfort, or chest pain). INTERVENTIONS: Patients
      were randomised to receive either ibuprofen 600 mg three times daily, amoxicillin
      clavulanic acid 500 mg/125 mg three times daily, or placebo three times daily for
      10 days. The duration of symptoms was measured with a diary card. MAIN OUTCOME
      MEASURE: Number of days with frequent cough after the randomisation visit.
      RESULTS: 416 participants were randomised (136 to ibuprofen, 137 to antibiotic,
      and 143 to placebo) and 390 returned their symptom diaries fully completed. The
      median number of days with frequent cough was slightly lower among patients
      assigned to ibuprofen (9 days, 95% confidence interval 8 to 10 days) compared
      with those receiving amoxicillin-clavulanic acid (11 days, 10 to 12 days) or
      placebo (11 days, 8 to 14 days), albeit without statistically significant
      differences. Neither amoxicillin-clavulanic acid nor ibuprofen increased the
      probability of cough resolution (hazard ratio 1.03, 95% confidence interval 0.78
      to 1.35 and 1.23, 0.93 to 1.61, respectively) compared with placebo. Adverse
      events were observed in 27 patients, and were more common in the antibiotic arm
      (12%) than ibuprofen or placebo arms (5% and 3%, respectively; P<0.01).
      CONCLUSION: No significant differences were observed in the number of days with
      cough between patients with uncomplicated acute bronchitis and discoloured sputum
      treated with ibuprofen, amoxicillin-clavulanic acid, or placebo. TRIAL
      REGISTRATION: Current Controlled Trials ISRCTN07852892.

PMID- 24097131
TI  - Are new technologies in infertility treatment always good news?

PMID- 24097132
TI  - Radiologist is struck off after failing to spot pathology that "should have been
      obvious to even a trainee".

PMID- 24097133
TI  - Isolation and functional characterization of a delta 6-desaturase gene from the
      pike eel (Muraenesox cinereus).
AB  - Stearidonic acid (STA; 18:4n-3) and gamma-linolenic acid (GLA; 18:3n-6) are
      significant intermediates in the biosynthetic pathway for the very-long-chain
      polyunsaturated fatty acids of eicosapentaenoic acid (EPA; 20:5n-3) and
      arachidonic acid (ARA; 20:4n-6), respectively. To develop a sustainable system
      for the production of dietary polyunsaturated fatty acids, we focused on the
      action of the enzyme delta 6-desaturase (D6DES) on the essential acids, linoleic
      acid (LA; 18:2n-6) and alpha-linolenic acid (ALA; 18:3n-3). A 1,335-bp full
      length cDNA encoding D6DES (McD6DES) was cloned from Muraenesox cinereus using
      degenerate PCR and RACE-PCR methods. To investigate the enzymatic activity of
      McD6DES in the production of n-6 and n-3 fatty acids, a recombinant plasmid
      expressing McD6DES (pYES-McD6DES) was transformed into and expressed in
      Saccharomyces cerevisiae. The exogenously expressed McD6DES produced GLA and STA
      at conversion rates of 14.2% and 45.9%, respectively, from the exogenous LA and
      ALA substrates. These results indicate that McD6DES is essentially a delta 6
      desaturase involved in very-long-chain polyunsaturated fatty acid synthesis. 

PMID- 24097134
TI  - Vigna angularis inhibits IL-6-induced cellular signalling and ameliorates
      collagen-induced arthritis.
AB  - OBJECTIVES: The present study was conducted in order to assess whether extracts
      or isolated compounds from Vigna angularis were able to suppress IL-6 signalling
      and to show the therapeutic effect on collagen-induced arthritis (CIA) in mice.
      METHODS: The effect of V. angularis on IL-6 signalling was studied by measuring
      Stat3-dependent luciferase activity, expression of inflammation-related genes,
      and phosphorylation of Janus kinase 2 (JAK2), signal transducer and activator of
      transcription 3 (STAT3) and extracellular signal-regulated kinase (ERK) induced
      by IL-6. CIA was induced by immunizing with bovine type II collagen. V. angularis
      extract (VAE) was administrated orally at 50 and 100 mg/kg from day 1 to day 28.
      Induction of arthritis was evaluated with a visual scoring system and
      histological analysis. RESULTS: Extracts or two triterpenoid compounds from V.
      angularis showed potent inhibitory effects on pSTAT3-inducible luciferase
      activity, STAT3 tyrosine phosphorylation and the expression of inflammation
      related genes induced by IL-6. Administration of VAE significantly suppressed the
      progression of CIA, accompanied by a reduced antibody response to type II
      collagen and protection from tissue damage in knee joints. CONCLUSION:
      Administration of VAE has a therapeutic effect on CIA and this effect is
      associated with the inhibitory activity on IL-6/STAT3 signalling. These results
      suggest that extracts or compounds from V. angularis could be a useful treatment
      for diseases related to IL-6, including RA.

PMID- 24097135
TI  - Kinematic, kinetic and electromyographic response to customized foot orthoses in
      patients with tibialis posterior tenosynovitis, pes plano valgus and rheumatoid
      arthritis.
AB  - OBJECTIVE: To describe the effect of customized foot orthoses (FOs) on the
      kinematic, kinetic and EMG features in patients with RA, tibialis posterior (TP)
      tenosynovitis and associated pes plano valgus. METHODS: Patients with RA and US
      confirmed tenosynovitis of TP underwent gait analysis, including three
      dimensional (3D) kinematics, kinetics, intramuscular EMG of TP and surface EMG of
      tibialis anterior, peroneus longus, soleus and medial gastrocnemius. Findings
      were compared between barefoot and shod with customized FO conditions. RESULTS:
      Ten patients with RA with a median (range) disease duration of 3 (1-18) years
      were recruited. Moderate levels of foot pain and foot-related impairment and
      disability were present with moderately active disease states. Altered timing of
      the soleus (P = 0.05) and medial gastrocnemius (P = 0.02) and increased magnitude
      of tibialis anterior (P = 0.03) were noted when barefoot was compared with shod
      with FO. Trends were noted for reduced TP activity in the contact period (P =
      0.09), but this did not achieve statistical significance. Differences in foot
      motion characteristics were recorded for peak rearfoot eversion (P = 0.01), peak
      rearfoot plantarflexion (P < 0.001) and peak forefoot abduction (P = 0.02) in the
      shod with FOs compared with barefoot conditions. No differences in kinetic
      variables were recorded. CONCLUSION: This study has demonstrated, for the first
      time, alterations in muscle activation profiles and foot motion characteristics
      in patients with RA, pes plano valgus and US-confirmed TP tenosynovitis in
      response to customized FOs. Complex adaptations were evident in this cohort and
      further work is required to determine whether these functional alterations lead
      to improvements in patient symptoms.

PMID- 24097136
TI  - Prolonged QTc interval predicts all-cause mortality in patients with rheumatoid
      arthritis: an association driven by high inflammatory burden.
AB  - OBJECTIVE: RA associates with an increased rate of sudden cardiac death (SCD). A
      prolonged QTc interval has been associated with arrhythmogenic and SCD in
      patients with long QT syndrome. Despite the previously reported contemporary
      association of CRP with SCD, thus far no studies have examined the association of
      QTc with mortality in RA, a condition characterized by high inflammatory burden.
      The aim of this study was to examine the role of electrocardiography (QT
      corrected interval) in predicting all-cause mortality in patients with RA who
      have an increased rate of SCD and a high inflammatory burden. METHODS: Three
      hundred and fifty-seven RA patients with detailed baseline clinical
      characterization and 12-lead ECGs were followed up for a mean of 73.0 (S.D. 18.3)
      months. Linear and Cox regression analyses were used to identify variables that
      associate with QTc and examine its association with all-cause mortality. RESULTS:
      The patients' mean age was 60.6 (S.D. 12.0) years, 267 (74.8%) were females and
      54 (15.1%) died during the follow-up period. Age (beta = 0.231, P < 0.001),
      gender (beta = 0.137, P = 0.008) and CRP (beta = 0.144, P = 0.006) associated
      independently with QTc in RA patients. The crude hazard ratio (HR) for total
      mortality per 50-ms increase in QTc was 2.17 (95% CI 1.21, 3.90). This
      association remained significant [HR = 2.18 (95% CI 1.09, 4.35)] after adjustment
      for identified confounders (cardiovascular and RA specific), but was lost [HR =
      1.73 (95% CI 0.83, 3.62)] when CRP was included in the model. CONCLUSION: A 50-ms
      increase in QTc interval associates with a doubling of the hazard for all-cause
      mortality in patients with RA. The observed contemporary association of QTc with
      CRP levels indicates a potentially hazardous interplay between inflammation and
      arrhythmogenesis. Future studies are needed to confirm the above findings and
      explore underlying mechanisms.

PMID- 24097137
TI  - The detection of inherent homologous recombination between repeat sequences in H.
      pylori 26695 by the PCR-based method.
AB  - Helicobacter pylori infects more than half of the world's population, making it
      the most widespread infection of bacteria. It has high genetic diversity and has
      been considered as one of the most variable bacterial species. In the present
      study, a PCR-based method was used to detect the presence and the relative
      frequency of homologous recombination between repeat sequences (>500 bp) in H.
      pylori 26695. All the recombinant structures have been confirmed by sequencing.
      The inversion generated between inverted repeats showed distinct features from
      the recombination for duplication or deletion between direct repeats. Meanwhile,
      we gave the mathematic reasoning of a general formula for the calculation of
      relative recombination frequency and indicated the conditions for its
      application. This formula could be extensively applied to detect the frequency of
      homologous recombination, site-specific recombination, and other types of
      predictable recombination. Our results should be helpful for better understanding
      the genome evolution and adaptation of bacteria. 

PMID- 24097138
TI  - Does access to role models influence future career choice? Impact of psychiatry
      teaching on recently graduated doctors in the United Kingdom.
AB  - OBJECTIVE: The authors determined who provides formal psychiatry teaching to
      newly-qualified doctors and whether the amount of such teaching correlates to a
      later career preference for psychiatry. METHODS: Data were collected on the
      cohort starting work in 2010 until applying to a specialty training program 16
      months later. Total hours of psychiatry teaching was compared with the number
      choosing a residency in the same specialty. RESULTS: A total of 19 hospitals in
      northwest England provided teaching programs for their interns and first-year
      residents (U.K. foundation doctors); 15 provided information on doctors' later
      specialty choice. Only 2.3% of teaching was dedicated to psychiatry. Doctors led
      a higher proportion of medicine or surgery sessions (63%) than those on
      psychiatry (48%). Provision of psychiatry teaching was associated with entering
      psychiatry residency. CONCLUSIONS: Hospitals providing the most formal psychiatry
      training have the highest proportions matriculating into a psychiatry residency.

PMID- 24097139
TI  - Room-temperature silver-containing liquid metal salts with nitrate anions.
AB  - The synthesis, structural, thermal and electrochemical properties of fluorine
      free silver-containing ionic liquids are presented. The ionic liquid cations are
      formed by a silver(i) ion surrounded by two 1-alkylimidazole ligands, with the
      counter anions being nitrate ions. Depending on the alkyl chain length, the
      complexes were found to be liquids at room temperature or melting slightly above
      this. For the solid compounds it was possible to elucidate the structure by
      single crystal X-ray analysis. The ionic liquids are electroactive, have good
      mass transport properties and can be used for the electrodeposition of silver at
      high current densities. The thermal properties and stability of these compounds
      were tested by differential scanning calorimetry and thermogravimetric analysis.
      The viscosity of the ionic liquids follows a Vogel-Tamman-Fulcher relationship as
      a function of temperature. The electrochemical properties of the complexes were
      tested by cyclic voltammetry and the resulting electrodeposits were examined
      using scanning electron microscopy and atomic force microscopy. 

PMID- 24097140
TI  - A scoping analysis of peer-reviewed literature about linkages between aquaculture
      and determinants of human health.
AB  - For many of the world's poor, aquatic products are critical for food security and
      health. Because the global population is increasing as wild aquatic stocks are
      declining, aquaculture is an increasingly important source of aquatic products.
      We undertook a scoping review of the English-language peer-reviewed literature to
      evaluate how the research community has examined the impacts of aquaculture on
      four key determinants of human health: poverty, food security, food production
      sustainability, and gender equality. The review returned 156 primary research
      articles. Most research (75%) was focused in Asia, with limited research from
      Africa (10%) and South America (2%). Most research (80%) focused on freshwater
      finfish and shrimp production. We used qualitative content analysis of records
      which revealed 11 themes: famer income; the common environment; shared resources;
      integrated farming/ polyculture; employment; extensive vs. intensive production;
      local vs. distant ownership; food security; income equity; gender equality; and
      input costs. We used quantitative content analysis of records and full-text
      publications about freshwater finfish and shrimp aquaculture to record the
      frequency with which themes were represented and the positive or negative impacts
      of aquaculture associated with each theme. Scatter plots showed that no theme was
      identified in more than half of all articles and publications for both production
      types. Farmer income was a theme that was identified commonly and was positively
      impacted by both shrimp and fresh water finfish aquaculture. Polyculture,
      employment, and local ownership were identified less often as themes, but were
      also associated with positive impacts. The common environment and shared
      resources were more common themes in shrimp aquaculture than freshwater finfish
      aquaculture research, while polyculture and local ownership were more common
      themes in freshwater finfish aquaculture than shrimp aquaculture. Gender
      equality, employment, and food security were themes found in a lower percentage
      of records than full-text publications for both production types. 

PMID- 24097141
TI  - National survey of sensory features in children with ASD: factor structure of the
      sensory experience questionnaire (3.0).
AB  - This national online survey study characterized sensory features in 1,307
      children with autism spectrum disorder (ASD) ages 2-12 years using the Sensory
      Experiences Questionnaire Version 3.0 (SEQ-3.0). Using the SEQ-3.0, a
      confirmatory factor analytic model with four substantive factors of hypothesized
      sensory response patterns (i.e., hyporesponsiveness; hyperresponsiveness; sensory
      interests, repetitions and seeking behaviors; enhanced perception), five method
      factors of sensory modalities (i.e., auditory, visual, tactile,
      gustatory/olfactory, vestibular/proprioceptive), and one of social context were
      tested with good model fit. Child and family characteristics associated with the
      sensory response patterns were explored. The effect of sensory response patterns
      on autism severity was tested, controlling for key child and family
      characteristics. The SEQ-3.0 demonstrates an empirically valid factor structure
      specific to ASD that considers sensory response patterns, modalities, and social
      context. 

PMID- 24097142
TI  - Reduced interhemispheric connectivity in childhood autism detected by
      electroencephalographic photic driving coherence.
AB  - The EEG coherence among 14 scalp points during intermittent photic stimulation at
      11 fixed frequencies of 3-24 Hz was studied in 14 boys with autism, aged 6-14
      years, with relatively intact verbal and intellectual functions, and 19 normally
      developing boys. The number of interhemispheric coherent connections pertaining
      to the 20 highest connections of each individual was significantly lower in
      autistic patients than in the control group at all the EEG beta frequencies
      corresponding to those of stimulation. The coefficient of coherence values
      between homologous occipital, parietal and central areas at the same frequencies
      were also lower in the autistic group in both mono- and bipolar montages due to a
      deficit in reactive photic driving increase. No differences between the groups
      were observed in the spontaneous EEG.

PMID- 24097143
TI  - [Endoscopic diagnosis of superficial esophageal squamous cell carcinoma].

PMID- 24097144
TI  - [Up to date of ESD for esophageal cancer].

PMID- 24097145
TI  - [Histopathological diagnosis and problem of intraepithelial neoplasia of the
      esophagus].

PMID- 24097146
TI  - [High risk groups for esophageal squamous cell carcinoma in Japanese].

PMID- 24097147
TI  - [The cutting edge in diagnosis and treatment of superficial esophageal squamous
      cell carcinoma. Discussion].

PMID- 24097148
TI  - [The impact of guidelines for the management of acute cholecystitis in a rural
      area of Japan].
AB  - We monitored the management of acute cholecystitis in a rural area of Japan to
      determine the effectiveness of new guidelines for the management of acute
      cholecystitis and cholangitis. Between January 2000 and September 2011, 366
      patients were treated for acute cholecystitis. Of these, 59 had common bile duct
      stones (CBDS) and 307 did not. Patients in both groups were further subdivided
      into two groups: a before guidelines group (BGG; n=153) and an after guideline
      group (AGG; n=154). Among the patients without CBDS, early cholecystectomy was
      more common in the AGG group (n=53) than in the BGG group. Furthermore, the
      length of hospital stay was four days shorter in the AGG group than in the BGG
      group (n=23). Among the patients with CBDS, the timing of cholecystectomy after
      endoscopic retrograde cholangiography was seven days earlier in the AGG group
      than in the BGG group. Even in a rural area of Japan, early cholecystectomy
      appears safe and can decrease the length of hospital stay. 

PMID- 24097149
TI  - [A case of calcineurin-inhibitor induced pain syndrome associated with tacrolimus
      therapy for ulcerative colitis].
AB  - A 23-year-old woman was admitted with a relapse of ulcerative colitis. Tacrolimus
      therapy was initiated following inadequate response to corticosteroid therapy.
      Although the symptoms partially improved, she suddenly developed severe pain
      localized to the lower limbs on day 16 of tacrolimus therapy. By day 17, she was
      unable to move. Magnetic resonance imaging revealed born marrow edema in the
      lower limbs. We suspected calcineurin-inhibitor induced pain syndrome (CIPS) due
      to tacrolimus therapy. The pain improved within approximately four weeks of
      tacrolimus cessation. CIPS that is not associated with organ transplantation is a
      rare occurrence. Here we report a rare case of CIPS that was caused by tacrolimus
      therapy in a patient with ulcerative colitis. 

PMID- 24097150
TI  - [A case of primary gastric malignant lymphoma with chylous ascites].
AB  - An 87-year-old man presented with appetite loss and abdominal distension. Routine
      blood tests revealed hypoproteinemia. Abdominal computed tomography revealed
      ascites, which was subsequently drained. Biochemical analysis of the ascitic
      fluid detected chyle. Esophagogastroduodenoscopy revealed nodular swelling of the
      mucosa, swelling folds, and widespread erosions in the stomach. Stage I diffuse
      large B-cell gastric malignant lymphoma was diagnosed on the basis of the Lugano
      International Conference classification system. Six courses of R-CHOP [rituximab,
      cyclophosphamide, hydroxydaunorubicin (doxorubicin), vincristine (Oncovin((r))),
      and prednisolone] therapy were administered, following which complete remission
      was achieved and the chylous ascites mostly disappeared. 

PMID- 24097151
TI  - [A case of gastric cancer associated with systemic lupus erythematosus and
      nephrotic syndrome].
AB  - A 72-year-old man with a complaint of lower limb edema was admitted to our
      hospital. Investigations revealed anemia, a decreased serum albumin level
      (1.7g/dl), and an increased urinary protein volume (7.4g/day), leading to a
      diagnosis of nephrotic syndrome. He also tested positive for anti-nuclear
      antibody and anti-DNA antibody, fulfilling the criteria for systemic lupus
      erythematosus (SLE). Endoscopy revealed type 2 advanced gastric cancer at the
      greater curvature of the antrum of the stomach. We performed distal gastrectomy
      and an open right renal biopsy without preoperative treatment. Histopathological
      examination of the resected stomach specimens revealed adenocarcinoma.
      Immunohistochemistry of the kidney specimen suggested membranous lupus nephritis.
      After surgery, his urinary protein volume gradually decreased and lower limb
      edema improved in the absence of any specific treatment for nephrotic syndrome or
      SLE. 

PMID- 24097152
TI  - [Small bowel obstruction and gastric ulceration resulting from rice cake
      ingestion -computed tomography diagnosis in eight patients-].
AB  - Here we report the cases of eight patients who developed small bowel obstruction
      and/or gastric ulcers after ingesting rice cake, the traditional Asian food, and
      were managed conservatively. This report adds to the existing literature on
      gastrointestinal disorders induced by rice cake ingestion, which are
      characterized by gastrointestinal obstruction, perforation, and ulceration and
      are occasionally accompanied by peritonism. These conditions tend to occur in 50
      60-year-old males who wear dentures or eat rapidly. Therapeutically, hard rice
      cake remnants in the upper gastrointestinal tract can be broken up by endoscopic
      snaring and can be detected by computed tomography as homogeneous high-density
      material at approximately 145 (range:120-206) Hounsfield units. 

PMID- 24097153
TI  - [A case of acute autoimmune hepatitis associated with autoimmune hemolytic
      anemia].
AB  - A 61-year-old female was admitted to our hospital with severe jaundice and
      anemia. She was diagnosed with severe acute hepatitis secondary to autoimmune
      hepatitis (AIH) on the basis of positive anti-nuclear antibody titers, high serum
      IgG levels, and liver biopsy. Autoimmune hemolytic anemia (AIHA) was diagnosed
      because of the presence of reticulocytosis, decreased haptoglobin, positive
      direct Coombs test, and erythroid hyperplasia in the bone marrow. Although AIH
      occurs in association with various immunological disorders, an association with
      AIHA is rarely reported. We report a rare case of severe AIH associated with
      AIHA. 

PMID- 24097154
TI  - [Two cases of lymphoepithelial cyst of the pancreas confirmed by contrast
      enhanced endoscopic ultrasound].
AB  - We report our experience with two cases of lymphoepithelial cysts (LECs) of the
      pancreas. Both patients were in their sixties. Contrast-enhanced computed
      tomography revealed masses in the pancreas with multilocular cystic lesions.
      Endoscopic ultrasound (EUS) findings presented highly echo-dense structures in
      the cystic masses; however, contrast-enhanced EUS revealed only the septum inside
      each mass without enhancing the dense structures. Contrast-enhanced EUS was
      useful for defining the contents in the cystic lesions; therefore, it may be
      useful for the diagnosis of LEC. 

PMID- 24097155
TI  - [Conservative management of a ruptured inferior pancreaticoduodenal artery
      aneurysm associated with celiac artery occlusion].
AB  - A 45-year-old female presented at our hospital with a one-day history of upper
      abdominal pain. Abdominal computed tomography (CT) revealed that the root of the
      celiac artery was obstructed and that a large hematoma was present in the
      retroperitoneum. The patient was diagnosed with retroperitoneal hemorrhage
      associated with the rupture of an inferior pancreaticoduodenal artery aneurysm,
      which was caused by increased blood flow in the pancreaticoduodenal arterial
      arcade. Because the patient's general condition was stable, she was managed
      conservatively and discharged on achieving remission after a month. Follow-up CT
      revealed spontaneous resolution of the celiac artery obstruction and aneurysm.
      The celiac artery obstruction in this case was assumed to be caused by segmental
      arterial mediolysis. 

PMID- 24097156
TI  - The Cope rearrangement of gem-dimethyl substituted divinylcyclopropanes.
AB  - The reactivity of a range of substituted divinylcyclopropanes towards the thermal
      Cope rearrangement has been examined. The effects of gem-dimethyl substitution on
      the cyclopropane, the alkene geometry, the relative stereochemistry of the
      cyclopropane and the steric and electronic effects of a range of functional
      groups were all examined, and the methods developed were used to synthesise a
      range of functionalised 1,4-cycloheptadienes in high yields. 

PMID- 24097157
TI  - Structure and function of voltage-gated sodium channels at atomic resolution.
AB  - Voltage-gated sodium channels initiate action potentials in nerve, muscle and
      other excitable cells. Early physiological studies described sodium selectivity,
      voltage-dependent activation and fast inactivation, and developed conceptual
      models for sodium channel function. This review article follows the topics of my
      2013 Sharpey-Schafer Prize Lecture and gives an overview of research using a
      combination of biochemical, molecular biological, physiological and structural
      biological approaches that have elucidated the structure and function of sodium
      channels at the atomic level. Structural models for voltage-dependent activation,
      sodium selectivity and conductance, drug block and both fast and slow
      inactivation are discussed. A perspective for the future envisions new advances
      in understanding the structural basis for sodium channel function and the
      opportunity for structure-based discovery of novel therapeutics.

PMID- 24097158
TI  - Integrative physiological and computational approaches to understand autonomic
      control of cerebral autoregulation.
AB  - The brain requires steady delivery of oxygen and glucose, without which
      neurodegeneration occurs within minutes. Thus, the ability of the cerebral
      vasculature to maintain relatively steady blood flow in the face of changing
      systemic pressure, i.e. cerebral autoregulation, is critical to
      neurophysiological health. Although the study of autoregulation dates to the
      early 20th century, only the recent availability of cerebral blood flow measures
      with high temporal resolution has allowed rapid, beat-by-beat measurements to
      explore the characteristics and mechanisms of autoregulation. These explorations
      have been further enhanced by the ability to apply sophisticated computational
      approaches that exploit the large amounts of data that can be acquired. These
      advances have led to unique insights. For example, recent studies have revealed
      characteristic time scales wherein cerebral autoregulation is most active, as
      well as specific regions wherein autonomic mechanisms are prepotent. However,
      given that effective cerebral autoregulation against pressure fluctuations
      results in relatively unchanging flow despite changing pressure, estimating the
      pressure-flow relationship can be limited by the error inherent in computational
      models of autoregulatory function. This review focuses on the autonomic neural
      control of the cerebral vasculature in health and disease from an integrative
      physiological perspective. It also provides a critical overview of the current
      analytical approaches to understand cerebral autoregulation. 

PMID- 24097159
TI  - The possible mechanisms by which maternal hypothyroidism impairs insulin
      secretion in adult male offspring in rats.
AB  - Previous studies have recently shown that maternal hypothyroidism leads to
      impaired glucose metabolism and reduced insulin secretion in adult offspring in
      rats. The aim of this study was to locate the defect in the insulin secretion
      pathway induced by maternal hypothyroidism. Pregnant Wistar rats were divided
      into two groups; the control group consumed water, while the hypothyroid (FH)
      group received water containing 0.025% 6-propyl-2-thiouracil during gestation. An
      intravenous glucose tolerance test was carried out on 5-month-old male offspring.
      In in vitro studies, the effects of various secretagogues and inhibitors acting
      at different levels of the insulin secretion cascade were investigated, and
      insulin content, insulin secretion and glucokinase activity of the islets were
      compared. Although insulin content of the FH islets did not differ from that of
      control islets, insulin secretion from FH islets was reduced when it was
      challenged by glucose or arginine. Compared with control islets, activities of
      both hexokinase and glucokinase were also significantly decreased in the FH
      islets. Although, in both groups, increasing glibenclamide and nifedipine
      concentrations in the presence of 16.7 mmol l(-1) glucose increased and decreased
      insulin secretion, respectively, the percentage of changes in secretion of FH
      islets was significantly lower compared with control islets. The response of FH
      islets to high extracellular potassium concentration and diazoxide was also
      significantly lower than that of the control islets. These findings demonstrate
      that impaired insulin secretion in the FH group is probably related to
      alterations in different steps of the insulin secretion pathway and not in the
      insulin pool of beta-cells. 

PMID- 24097160
TI  - Potential roles of ATP and local neurons in the monitoring of blood O2 content by
      rat aortic bodies.
AB  - Aortic bodies are arterial chemoreceptors presumed to monitor blood O2 content by
      unknown mechanisms, in contrast to their well-studied carotid body counterparts,
      which monitor PO2 and /pH. We recently showed that rat aortic body chemoreceptors
      (type I cells), located at the left vagus-recurrent laryngeal nerve bifurcation,
      responded to PO2 and PCO2 /pH in a manner similar to carotid body type I cells.
      These aortic bodies are uniquely associated with a group of local neurons, which
      are also sensitive to these stimuli. Here, we hypothesized that these local
      neurons may contribute to monitoring blood O2 content. During perforated patch
      recordings, ATP, known to be released from (carotid body) type I cells and red
      blood cells during hypoxia, induced inward currents and excited ~ 45% of local
      neurons (EC50 ~ 1 MUm), mainly via heteromeric P2X2/3 purinoceptors. While ATP
      also induced a rise in intracellular [Ca(2+)] in a subpopulation of these
      neurons, almost all of them responded to nicotinic cholinergic agonists. During
      paired recordings, several juxtaposed neurons showed strong bidirectional
      electrical coupling, suggesting a local co-ordination of electrical activity.
      Perfusion with Evans Blue dye resulted in labelling of aortic body paraganglia,
      suggesting they have ready access to circulatory factors, e.g. ATP released from
      red blood cells during hypoxia. When combined with confocal immunofluorescence,
      the dye-labelled regions coincided with areas containing tyrosine hydroxylase
      positive type I cell clusters and P2X2-positive nerve endings. We propose a
      working model whereby local neurons, red blood cells, ATP signalling and low
      blood flow contribute to the unique ability of the aortic body to monitor blood
      O2 content.

PMID- 24097168
TI  - External defibrillation on an implantable defibrillator.

PMID- 24097169
TI  - Implications of dedicated tracheostomy care nurse program on outcomes.
AB  - PURPOSE: Tracheostomy is a common occurrence in intensive care units (ICU), and a
      greater number of tracheostomized patients are shifted from ICU to non-critical
      areas. Tracheostomy care needs a multidisciplinary approach, particularly
      involving the nurses, and complications such as tube blockage, infection, and
      bleeding can be prevented by good bedside nursing. The aim was to study the
      impact of dedicated tracheostomy care nurse program on outcomes of
      tracheostomized patients. METHODS: A tracheostomy care nurse program was
      improvised by the critical care physicians, with the objective of improving care
      of tracheostomized patients, wherein nursing staff from noncritical areas were
      selected for training purposes. The training included evidence-based knowledge
      and hands-on training. After a written assessment and a skill test, they were
      certified as 'Tracheostomy Care Nurse.' At least one of the tracheostomy care
      nurses was supposed to be responsible for tracheostomy care in specific wards.
      Comparative data of two periods, a pre-intervention period from January 2011 to
      November 2011 and a post-intervention period from December 2011 to October 2012,
      were analyzed. RESULTS: During the pre-intervention period, of 82 tracheostomized
      patients, 28 (34.15 %) had complications including 20 (24.39 %) readmissions to
      the ICU. During the post-intervention period, 107 patients had a tracheostomy, of
      which 7 (6.54 %) had complications with only 2 (1.87 %) readmissions, which was
      significant (p < 0.05). Decannulations nonsignificantly increased during the post
      intervention period (25 vs. 16 %, p > 0.05). The average length of hospital stay
      (ALOS) decreased from 36 to 27 days (p < 0.05). CONCLUSION: The support of a
      specialist tracheostomy nurse can decrease complication rates and readmissions to
      the ICU and reduce ALOS.

PMID- 24097170
TI  - Recruitment order of quadriceps motor units: femoral nerve vs. direct quadriceps
      stimulation.
AB  - INTRODUCTION: To investigate potential differences in the recruitment order of
      motor units (MUs) in the quadriceps femoris when electrical stimulation is
      applied over the quadriceps belly versus the femoral nerve. METHODS: M-waves and
      mechanical twitches were evoked using femoral nerve stimulation and direct
      quadriceps stimulation of gradually increasing intensity from 20 young, healthy
      subjects. Recruitment order was investigated by analysing the time-to-peak twitch
      and the time interval from the stimulus artefact to the M-wave positive peak (M
      wave latency) for the vastus medialis (VM) and vastus lateralis (VL) muscles.
      RESULTS: During femoral nerve stimulation, time-to-peak twitch and M-wave latency
      decreased consistently (P < 0.05) with increasing stimulus intensity, whereas,
      during graded direct quadriceps stimulation, time-to-peak twitch and VL M-wave
      latency did not show a clear trend (P > 0.05). For the VM muscle, M-wave latency
      decreased with increasing stimulation level for both femoral nerve and direct
      quadriceps stimulation, whereas, for the VL muscle, the variation of M-wave
      latency with stimulus intensity was different for the two stimulation geometries
      (P < 0.05). CONCLUSIONS: Femoral nerve stimulation activated MUs according to the
      size principle, whereas the recruitment order during direct quadriceps
      stimulation was more complex, depending ultimately on the architecture of the
      peripheral nerve and its terminal branches below the stimulating electrodes for
      each muscle. For the VM, MUs were orderly recruited for both stimulation
      geometries, whereas, for the VL muscle, MUs were orderly recruited for femoral
      nerve stimulation, but followed no particular order for direct quadriceps
      stimulation.

PMID- 24097171
TI  - Cycling time to failure is better maintained by cold than contrast or
      thermoneutral lower-body water immersion in normothermia.
AB  - PURPOSE: To examine the effects of four commonly used recovery treatments applied
      between two bouts of intense endurance cycling on the performance of the second
      bout in normothermia (~21  degrees C). METHODS: Nine trained men completed two
      submaximal exhaustive cycling bouts (Ex1 and Ex2: 5 min at ~50 % [Formula: see
      text] peak, followed by 5 min at ~60 % [Formula: see text] peak and then ~80 %
      [Formula: see text] peak to failure) separated by 30 min of (a) cold water
      immersion at 15  degrees C (C15), (b) contrast water therapy alternating 2.5 min
      at 8  degrees C and 2.5 min at 40  degrees C (CT), (c) thermoneutral water
      immersion at 34  degrees C (T34) and (d) cycling at ~40 % [Formula: see text]
      peak (AR). RESULTS: Exercise performance, cardiovascular and metabolic responses
      during Ex1 were similar among all trials. However, time to failure (~80 %
      [Formula: see text] peak bout) during Ex2 was significantly (P < 0.05) longer in
      C15 (18.0 +/- 1.6) than in CT (14.5 +/- 1.5), T34 (12.4 +/- 1.4) and AR (10.6 +/-
      1.0); and it was also longer (P < 0.05) in CT than AR. Core temperature and heart
      rate were significantly (P < 0.05) lower during the initial ~15 min of Ex2 during
      C15 compared with all other conditions but they reached similar levels at the end
      of Ex2. CONCLUSIONS: A 30 min period of C15 was more beneficial in maintaining
      intense submaximal cycling performance than CT, T34 and AR; and CT was also more
      beneficial than T34 and AR. These effects were not mediated by the effect of
      water immersion per se, but by the continuous (C15) or intermittent (CT)
      temperature stimulus (cold) applied throughout the recovery.

PMID- 24097172
TI  - Effect of chronic activity-based therapy on bone mineral density and bone
      turnover in persons with spinal cord injury.
AB  - PURPOSE: Osteoporosis is a severe complication of spinal cord injury (SCI). Many
      exercise modalities are used to slow bone loss, yet their efficacy is equivocal.
      This study examined the effect of activity-based therapy (ABT) targeting the
      lower extremities on bone health in individuals with SCI. METHODS: Thirteen men
      and women with SCI (age and injury duration = 29.7 +/- 7.8 and 1.9 +/- 2.7 years)
      underwent 6 months of ABT. At baseline and after 3 and 6 months of training,
      blood samples were obtained to assess bone formation (serum procollagen type 1 N
      propeptide (PINP) and bone resorption (serum C-terminal telopeptide of type I
      collagen (CTX), and participants underwent dual-energy X-ray absorptiometry scans
      to obtain total body and regional estimates of bone mineral density (BMD).
      RESULTS: Results demonstrated significant increases (p < 0.05) in spine BMD (+4.8
      %; 1.27 +/- 0.22-1.33 +/- 0.24 g/cm(2)) and decreases (p < 0.01) in total hip BMD
      (-6.1 %; 0.98 +/- 0.18-0.91 +/- 0.16 g/cm(2)) from 0 to 6 months of training. BMD
      at the bilateral distal femur (-7.5 to -11.0 %) and proximal tibia (- 8.0 to 
      11.2 %) declined but was not different (p > 0.05) versus baseline. Neither PINP
      nor CTX was altered (p > 0.05) with training. CONCLUSIONS: Chronic activity-based
      therapy did not reverse bone loss typically observed soon after injury, yet
      reductions in BMD were less than the expected magnitude of decline in lower
      extremity BMD in persons with recent SCI.

PMID- 24097173
TI  - Small effects of neck torsion on healthy human voluntary eye movements.
AB  - PURPOSE: Although several lines of research suggest that the head and eye
      movement systems interact, previous studies have reported that applying static
      neck torsion does not affect smooth pursuit eye movements in healthy controls.
      This might be due to several methodological issues. Here we systematically
      investigated the effect of static neck torsion on smooth pursuit and saccadic eye
      movement behavior in healthy subjects. METHODS: In twenty healthy controls, we
      recorded eye movements with video-oculography while their trunk was in static
      rotation relative to the head (7 positions from 45 degrees  to the left to 45
      degrees  to right). The subject looked at a moving dot on the screen. In two
      separate paradigms, we evoked saccadic and smooth pursuit eye movements, using
      both predictable and unpredictable target motions. RESULTS: Smooth pursuit gain
      and saccade peak velocity decreased slightly with increasing neck torsion. Smooth
      pursuit gains were higher for predictable target movements than for unpredictable
      target movements. Saccades to predictable targets had lower latencies, but
      reduced gains compared to saccades to unpredictable targets. No interactions
      between neck torsion and target predictability were observed. CONCLUSION:
      Applying static neck torsion has small effects on voluntary eye movements in
      healthy subjects. These effects are not modulated by target predictability.

PMID- 24097174
TI  - The impact of high-intensity intermittent exercise on resting metabolic rate in
      healthy males.
AB  - INTRODUCTION: High-intensity intermittent exercise training (HIT) may favourably
      alter body composition despite low training volumes and predicted energy
      expenditure (EE). PURPOSE: To characterise the acute impact of two common HIT
      protocols on EE and post-exercise oxygen consumption (11 h EPOC). METHODS: Oxygen
      consumption (l min(-1)), respiratory exchange ratio (RER) and EE were measured in
      nine healthy, lean males over 12 h under three conditions: control (CON), HIT1
      (10 * 1 min high-intensity cycling bouts followed by 1 min rest) and HIT2 (10 * 4
      min high-intensity cycling bouts followed by 2 min rest). RESULTS: Total exercise
      period EE during HIT1 (1,151 +/- 205 kJ) (mean +/- SD) was significantly lower
      than HIT2 (2,788 +/- 322 kJ; p < 0.001). EE within the 60 min after exercise was
      significantly albeit marginally higher after HIT1 (388 +/- 44 kJ; p = 0.02) and
      HIT2 (389 +/- 39 kJ; p = 0.01) compared with CON (329 +/- 39 kJ), with no
      difference between exercise conditions (p = 0.778). RER during this period was
      significantly lower in HIT1 (0.78 +/- 0.06; p = 0.011) and HIT2 (0.76 +/- 0.04; p
      = 0.004) compared with CON (0.87 +/- 0.06). During the 'slow phase' of EPOC (1.25
      9.75 h), there were no significant differences in EE (p = 0.07) or RER (p =
      0.173) between trials. CONCLUSIONS: Single HIT sessions notably increases EE
      during exertion; however, the influence on metabolic rate post-exercise is
      transient and relatively minor.

PMID- 24097175
TI  - Facet-dependent electrochemical properties of Co3O4 nanocrystals toward heavy
      metal ions.
AB  - We revealed an interesting facet-dependent electrochemical behavior toward heavy
      metal ions (HMIs) based on their adsorption behaviors. The (111) facet of Co3O4
      nanoplates has better electrochemical sensing performance than that of the (001)
      facet of Co3O4 nanocubes. Adsorption measurements and density-functional theory
      (DFT) calculations reveals that adsorption of HMIs is responsible for the
      difference of electrochemical properties. Our combined experimental and
      theoretical studies provide a solid hint to explain the mechanism of
      electrochemical detection of HMIs using nanoscale metal oxides. Furthermore, this
      study not only suggests a promising new strategy for designing high performance
      electrochemical sensing interface through the selective synthesis of nanoscale
      materials exposed with different well-defined facets, but also provides a deep
      understanding for a more sensitive and selective electroanalysis at nanomaterials
      modified electrodes. 

PMID- 24097178
TI  - Integration of genomics into the electronic health record: mapping terra
      incognita.

PMID- 24097182
TI  - Non-Descemet stripping Descemet membrane endothelial keratoplasty.
AB  - PURPOSE: To report a case of non-Descemet stripping Descemet membrane endothelial
      keratoplasty (nDMEK) in a patient with pseudophakic bullous keratopathy. METHODS:
      A 70-year-old man underwent an nDMEK in his right eye, which suffered from
      pseudophakic bullous keratopathy after a complicated cataract surgery was
      performed. Under local anesthesia, an 8-mm sized round Descemet membrane and
      endothelial cell graft (DMEK graft), harvested from an 85-year-old male donor
      cornea, were transplanted without stripping the recipient's Descemet membrane.
      The patient was examined at 1 week, 2 weeks, 3 weeks, 4 weeks, 2 months, 4
      months, and 6 months after the surgery took place. Optical coherence tomography,
      Scheimpflug imaging (Pentacam, Oculus), and specular microscopy were performed.
      RESULTS: Graft detachment was observed at 1 and 2 weeks after the surgery, but
      this was successfully resolved with C3F8 gas tamponade in the anterior chamber.
      Thereafter, no graft detachment was observed, and the cornea remained clear 6
      months after the surgery. The best-spectacle corrected visual acuity was improved
      from 20/100 to 20/25, and central corneal pachymetry was improved from 713 to 570
      um. No ocular complication was detected at the final visit. CONCLUSIONS: An nDMEK
      was successfully performed in a patient with pseudophakic bullous keratopathy and
      resulted in a good visual outcome.

PMID- 24097183
TI  - A comparison of anchored conjunctival rotation flap and conjunctival autograft
      techniques in pterygium surgery.
AB  - PURPOSE: To compare conjunctival autograft and anchored conjunctival rotation
      flap techniques, in terms of recurrence and complication rates, after performing
      a primary pterygium surgery. METHODS: Sixty patients who underwent pterygium
      surgery, which was performed on 1 eye (M:F = 25:35), either using conjunctival
      autograft (25 eyes) or anchored conjunctival rotation flap (35 eyes) techniques,
      were followed up postoperatively for a minimum period of 18 months. The anchored
      conjunctival rotation flap surgery was conducted by designing a conjunctival flap
      with a similar shape as that of the autograft, but with the preservation of the
      inferior limbal anchoring point (1 mm) by the incomplete cutting of the limbal
      area. After rotation of the flap around the anchoring point, the flap was
      tightened with sutures to cover the bare scleral area. Early postoperative
      complications, such as flap or graft edema and granuloma formation, were
      assessed. The recurrence rate of pterygium was evaluated, and a comparison was
      made between the 2 surgical techniques. RESULTS: The recurrence rate was 8.0% in
      the conjunctival autograft group and 8.6% in the anchored conjunctival rotational
      flap group (P = 0.659). However, the occurrence of flap or graft edema was lower
      for anchored conjunctival rotational flap surgery (14.3% vs. 72.0%, P < 0.001).
      No granuloma formation was observed in either group. CONCLUSIONS: The anchored
      conjunctival rotational flap surgery showed similar pterygium recurrence rates
      and a lower incidence of flap edema, while enabling simple recognition of flap
      orientation, compared with the conjunctival autograft technique.

PMID- 24097184
TI  - Using cyanoacrylate glue for corneal perforations: caution with use of a needle
      and syringe.

PMID- 24097185
TI  - Evaluation of lipid layer thickness measurement of the tear film as a diagnostic
      tool for Meibomian gland dysfunction.
AB  - PURPOSE: The LipiView interferometer (TearScience Inc, Morrisville, NC) is
      capable of delivering quantitative values of the tear-film lipid layer thickness
      (LLT). The purpose of this study was to investigate whether there is a
      correlation between the LLT and other diagnostic criteria for Meibomian gland
      dysfunction (MGD). METHODS: We performed a retrospective analysis of 110 patients
      (199 eyes) from our dry eye clinic. Subjective symptoms, break-up time (BUT),
      expressible Meibomian glands, and LLT were measured. RESULTS: There was a
      significant correlation between expressible Meibomian glands and LLT (r = 0.36, P
      < 0.0001). Also, a possible trend of inverse correlation between subjective
      symptoms (standard patient evaluation of eye dryness) and the LLT was observed;
      however, this was not significant (r = -0.13, P < 0.08). Analysis of the whole
      study collective revealed no correlation between the BUT and the LLT (r = 0.003,
      P = 0.97). A subgroup analysis of the patients with an LLT <= 60 showed a better
      correlation between the LLT and the BUT, which was marginally not significant (r
      = 0.21; P = 0.059). For a cut-off value of <= 75-nm LLT, we found a sensitivity
      of 65.8% and a specificity of 63.4% for the detection of an MGD. For a cut-off
      value of <= 60, the sensitivity was 47.9%, and the specificity was 90.2%.
      CONCLUSIONS: The positive correlation between the LLT and expressible meibomian
      glands found in this study suggests a higher probability of MGD in patients with
      a low LLT. This automated assessment of the LLT might be a suitable screening
      test for detecting MGD. However, further prospective studies are needed to
      confirm these results and to identify potential confounders.

PMID- 24097186
TI  - Wound anatomy after type 1 Boston KPro using oversized back plates.
AB  - PURPOSE: To compare the anatomy of the graft-host junction and anterior chamber
      angle after Boston Keratoprosthesis (KPro) placement using oversized (9.5-mm) and
      standard (8.5-mm) back plates. METHODS: Six patients with 9.5-mm titanium back
      plates and 10 patients with 8.5-mm titanium back plates were imaged by anterior
      segment optical coherence tomography 6 to 12 months after KPro placement. The
      location of the graft-host junction in relation to the back plate, the corneal
      thickness at the graft-host junction, and the anterior chamber angle were
      assessed. The clinical outcomes and incidence of retroprosthetic membrane (RPM)
      formation in this cohort were retrospectively evaluated. RESULTS: The oversized
      back plates completely covered the graft-host junction in all quadrants, allowing
      the complete apposition of the posterior surface of the carrier graft with the
      host cornea, with decreased graft-host junction wound thickness. The standard
      back plates covered the posterior aspect of the carrier graft but not the graft
      host junction or the host cornea, resulting in a significantly thicker graft-host
      junction. None of the patients with larger back plates developed a significant
      RPM during a 12-month follow-up period. One patient with a larger back plate
      developed a corneal melt at the KPro stem as a result of chronic exposure.
      CONCLUSIONS: Oversized KPro back plates effectively cover the graft-host junction
      without any adverse effects on angle anatomy or wound healing. This may be a
      strategy to provide better wound apposition, reduce RPM formation, and reduce
      angle closure from iris synechiae to the wound.

PMID- 24097187
TI  - Physiology of the pulmonary circulation and the right heart.
AB  - The pulmonary circulation is a high-flow and low-pressure circuit. The functional
      state of the pulmonary circulation is defined by pulmonary vascular pressure-flow
      relationships conforming to distensible vessel models with a correction for
      hematocrit. The product of pulmonary arterial compliance and resistance is
      constant, but with a slight decrease as a result of increased pulsatile hydraulic
      load in the presence of increased venous pressure or proximal pulmonary arterial
      obstruction. An increase in left atrial pressure is transmitted upstream with a
      ratio >=1 for mean pulmonary artery pressure and <=1 the diastolic pulmonary
      pressure. Therefore, the diastolic pressure gradient is more appropriate than the
      transpulmonary pressure gradient to identify pulmonary vascular disease in left
      heart conditions. Exercise is associated with a decrease in pulmonary vascular
      resistance and an increase in pulmonary arterial compliance. Right ventricular
      function is coupled to the pulmonary circulation with an optimal ratio of end
      systolic to arterial elastances of 1.5-2. 

PMID- 24097188
TI  - Chloride extrusion enhancers as novel therapeutics for neurological diseases.
AB  - The K(+)-Cl(-) cotransporter KCC2 is responsible for maintaining low Cl(-)
      concentration in neurons of the central nervous system (CNS), which is essential
      for postsynaptic inhibition through GABA(A) and glycine receptors. Although no
      CNS disorders have been associated with KCC2 mutations, loss of activity of this
      transporter has emerged as a key mechanism underlying several neurological and
      psychiatric disorders, including epilepsy, motor spasticity, stress, anxiety,
      schizophrenia, morphine-induced hyperalgesia and chronic pain. Recent reports
      indicate that enhancing KCC2 activity may be the favored therapeutic strategy to
      restore inhibition and normal function in pathological conditions involving
      impaired Cl(-) transport. We designed an assay for high-throughput screening that
      led to the identification of KCC2 activators that reduce intracellular chloride
      concentration ([Cl(-)]i). Optimization of a first-in-class arylmethylidine family
      of compounds resulted in a KCC2-selective analog (CLP257) that lowers [Cl(-)]i.
      CLP257 restored impaired Cl(-) transport in neurons with diminished KCC2
      activity. The compound rescued KCC2 plasma membrane expression, renormalized
      stimulus-evoked responses in spinal nociceptive pathways sensitized after nerve
      injury and alleviated hypersensitivity in a rat model of neuropathic pain. Oral
      efficacy for analgesia equivalent to that of pregabalin but without motor
      impairment was achievable with a CLP257 prodrug. These results validate KCC2 as a
      druggable target for CNS diseases.

PMID- 24097190
TI  - Collective memories of three wars in United States history in younger and older
      adults.
AB  - A collective memory is a representation of the past that is shared by members of
      a group. We investigated similarities and differences in the collective memories
      of younger and older adults for three major wars in U.S. history (the Civil War,
      World War II, and the Iraq War). Both groups were alive during the recent Iraq
      War, but only the older subjects were alive during World War II, and both groups
      learned about the Civil War from historical sources. Subjects recalled the 10
      most important events that occurred during each war and then evaluated the
      emotional valence, the relative importance, and their level of knowledge for each
      event. They also estimated the percentage of people that would share their memory
      of each event within their age group and the other age group. Although most
      historical events were recalled by fewer than 25 % of subjects, younger and older
      adults commonly recalled a core set of events for each war that conform to a
      narrative structure that may be fundamental to collective remembering. Younger
      adults showed greater consensus in the events that they recalled for all three
      wars, relative to older adults, but there was less consensus in both groups for
      the Iraq War. Whereas younger adults recalled more specific events of short
      duration, older adults recalled more extended and summarized events of long
      duration. Our study shows that collective memories can be studied empirically and
      can differ depending on whether the events are experienced personally or learned
      from historical sources. 

PMID- 24097189
TI  - Cold-inducible RNA-binding protein (CIRP) triggers inflammatory responses in
      hemorrhagic shock and sepsis.
AB  - A systemic inflammatory response is observed in patients undergoing hemorrhagic
      shock and sepsis. Here we report increased levels of cold-inducible RNA-binding
      protein (CIRP) in the blood of individuals admitted to the surgical intensive
      care unit with hemorrhagic shock. In animal models of hemorrhage and sepsis, CIRP
      is upregulated in the heart and liver and released into the circulation. In
      macrophages under hypoxic stress, CIRP translocates from the nucleus to the
      cytosol and is released. Recombinant CIRP stimulates the release of tumor
      necrosis factor-alpha (TNF-alpha) and HMGB1 from macrophages and induces
      inflammatory responses and causes tissue injury when injected in vivo. Hemorrhage
      induced TNF-alpha and HMGB1 release and lethality were reduced in CIRP-deficient
      mice. Blockade of CIRP using antisera to CIRP attenuated inflammatory cytokine
      release and mortality after hemorrhage and sepsis. The activity of extracellular
      CIRP is mediated through the Toll-like receptor 4 (TLR4)-myeloid differentiation
      factor 2 (MD2) complex. Surface plasmon resonance analysis indicated that CIRP
      binds to the TLR4-MD2 complex, as well as to TLR4 and MD2 individually. In
      particular, human CIRP amino acid residues 106-125 bind to MD2 with high
      affinity. Thus, CIRP is a damage-associated molecular pattern molecule that
      promotes inflammatory responses in shock and sepsis. 

PMID- 24097191
TI  - Estimating the health-care usage associated with osteoarthritis and rheumatoid
      arthritis in an older adult population in Ireland.
AB  - BACKGROUND: An ageing population leads to increasing prevalence of age-related
      chronic conditions that present challenges to the health-care services. Despite
      this, in countries including Ireland, little is known about the health-care
      impact of conditions such as osteoarthritis or rheumatoid arthritis amongst older
      adults. METHODS: A series of count models are developed to investigate the
      incremental health-care usage of individuals with either osteoarthritis or
      rheumatoid arthritis on the use of general practitioners (GP) services,
      outpatients' services, accident and emergency visits and inpatient nights.
      RESULTS: Both types of arthritic conditions lead to increased usage of GP and
      outpatients' services but not other hospital services. Differences in
      entitlements to care, as captured by the presence of a medical card in Ireland,
      lead to different health-care usage among arthritis sufferers. Translating the
      additional utilization into cost suggests a combined incremental annual cost of
      both types of arthritis of ?13.6 million. CONCLUSIONS: Osteoarthritis and
      rheumatoid arthritis present challenges to health-care services in the context of
      an ageing population. In the case of Ireland the burden falls predominantly on
      primary health-care and outpatient services. Within the context of changing
      health-care service provision in Ireland, the results of this study have
      implications for future planning of service delivery.

PMID- 24097192
TI  - Preventing infections in the ICU: one size does not fit all.

PMID- 24097193
TI  - Low-temperature structure anomalies in CuNCN. Manifestations of RVB phase
      transitions?
AB  - We propose a new frustrated Heisenberg antiferromagnetic model with spatially
      anisotropic exchange parameters Jc, Ja, and Jac, extending along the c, a, and a
      +/- c (c-a-ca model) lattice directions, and apply it to describe the fascinating
      physics of copper carbodiimide, CuNCN, assuming the resonating valence bond (RVB)
      type of its phases. This explains within a unified picture the intriguing absence
      of magnetic order in CuNCN. We further present a parameters-temperature phase
      diagram of the c-a-ca-RVB model in the high-temperature approximation. Eight
      different phases including Curie and Pauli paramagnets (respectively, in
      disordered and 1D- or Q1D-RVB phases) and (pseudo)gapped (quasi-Arrhenius)
      paramagnets (2D-RVB phases) are possible. By adding magnetostriction and elastic
      terms to the model, we derive possible structural manifestations of RVB phase
      transitions. Assuming a sequence of RVB phase transitions to occur in CuNCN with
      decreasing temperature, several anomalies observed in the temperature course of
      the lattice constants are explained.

PMID- 24097195
TI  - Rural residence and cancer outcomes in the United States: issues and challenges.
AB  - "Neighborhoods and health" research has shown that area social factors are
      associated with the health outcomes that patients with cancer experience across
      the cancer control continuum. To date, most of this research has been focused on
      the attributes of urban areas that are associated with residents' poor cancer
      outcomes with less focused on attributes of rural areas that may be associated
      with the same. Perhaps because there is not yet a consensus in the United States
      regarding how to define "rural," there is not yet an accepted analytic convention
      for studying issues of how patients' cancer outcomes may vary according to
      "rural" as a contextual attribute. The research that exists reports disparate
      findings and generally treats rural residence as a patient attribute rather than
      a contextual factor, making it difficult to understand what factors (e.g.,
      unmeasured individual poverty, area social deprivation, area health care
      scarcity) may be mediating the poor outcomes associated with rural (or non-rural)
      residence. Here, we review literature regarding the potential importance of rural
      residence on cancer patients' outcomes in the United States with an eye towards
      identifying research conventions (i.e., spatial and analytic) that may be useful
      for future research in this important area.

PMID- 24097196
TI  - Impact of rural residence on forgoing healthcare after cancer because of cost.
AB  - BACKGROUND: Routine follow-up care is recommended to promote the well-being of
      cancer survivors, but financial difficulties may interfere. Rural-urban
      disparities in forgoing healthcare due to cost have been observed in the general
      population; however, it is unknown whether this disparity persists among
      survivors. The purpose of this study was to examine rural-urban disparities in
      forgoing healthcare after cancer due to cost. METHODS: We analyzed data from
      7,804 cancer survivors in the 2006 to 2010 National Health Interview Survey.
      Logistic regression models, adjusting for sociodemographic and clinical
      characteristics, were used to assess rural-urban disparities in forgoing medical
      care, prescription medications, and dental care due to cost, stratified by age
      (younger: 18-64, older: 65+). RESULTS: Compared with urban survivors, younger
      rural survivors were more likely to forgo medical care (P < 0.001) and
      prescription medications (P < 0.001) due to cost; older rural survivors were more
      likely to forgo medical (P < 0.001) and dental care (P = 0.05). Rural-urban
      disparities did not persist among younger survivors in adjusted analyses;
      however, older rural survivors remained more likely to forgo medical [OR = 1.66,
      95% confidence interval (CI) = 1.11-2.48] and dental care (OR = 1.54, 95%CI =
      1.08-2.20). CONCLUSIONS: Adjustment for health insurance and other
      sociodemographic characteristics attenuates rural-urban disparities in forgoing
      healthcare among younger survivors, but not older survivors. Financial factors
      relating to healthcare use among rural survivors should be a topic of continued
      investigation. IMPACT: Addressing out-of-pocket costs may be an important step in
      reducing rural-urban disparities in healthcare, especially for older survivors.
      It will be important to monitor how healthcare reform efforts impact disparities
      observed in this vulnerable population.

PMID- 24097197
TI  - Seroepidemiology of high-risk HPV in HIV-negative and HIV-infected MSM: the H2M
      study.
AB  - BACKGROUND: Men who have sex with men (MSM), in particular HIV-infected MSM, are
      at increased risk for diseases related to human papilloma virus (HPV). Our goal
      was to assess the effect of HIV status on the presence of type-specific
      antibodies against seven high-risk HPV types in HPV-unvaccinated MSM. Moreover,
      we compared determinants of HPV seropositivity between HIV-negative and HIV
      infected MSM. METHODS: MSM >=18 years of age were recruited from the Amsterdam
      Cohort Studies, a sexually transmitted infection clinic, and an HIV-treatment
      center in Amsterdam, the Netherlands. Participants completed a risk-factor
      questionnaire; serum samples were analyzed using a fluorescent bead-based
      multiplex assay. RESULTS: MSM (n = 795) were recruited in 2010 to 2011; 758 MSM
      were included in this analysis. Median age was 40.1 years (interquartile range
      34.8-47.5) and 308 MSM (40.6%) were HIV-infected. Seroprevalence of HPV-16 was
      37.1% in HIV-negative and 62.7% in HIV-infected MSM (P < 0.001); seroprevalence
      of HPV-18 was 29.1% in HIV-negative MSM and 42.5% in HIV-infected MSM (P <
      0.001). Similar patterns of seroprevalence were observed for HPV types 31, 33,
      45, 52, and 58. In multivariable analyses, HPV seropositivity was associated with
      HIV infection [adjusted OR = 2.1; 95% confidence interval, 1.6-2.6]. In
      multivariable analyses stratified by HIV status, increasing age and number of
      lifetime male sex partners were significantly associated with HPV seropositivity
      in HIV-negative, but not HIV-infected MSM. CONCLUSIONS: Seroprevalence of high
      risk HPV types is high among unvaccinated MSM. IMPACT: HIV infection is a strong
      and independent determinant for HPV seropositivity, which we hypothesize is
      because of increased persistence of HPV infection in HIV-infected MSM.

PMID- 24097198
TI  - Plasma C-peptide, mammographic breast density, and risk of invasive breast
      cancer.
AB  - BACKGROUND: Insulin may promote breast cancer directly by stimulating the insulin
      receptor or indirectly by increasing the plasma concentration of active sex
      hormones. The association between insulin and breast density, a strong breast
      cancer risk factor, has not been thoroughly studied. We measured associations
      between c-peptide (a molar marker of insulin secretion), breast cancer risk, and
      breast density measurements in case-control studies nested within the Nurses'
      Health Study and Nurses' Health Study II cohorts. METHODS: Breast cancer
      associations were estimated with multivariate logistic regression models and then
      pooled across cohorts (total n = 1,084 cases and 1,785 controls). Mammographic
      density associations (percent dense area, dense area, and nondense area) were
      estimated as the difference in least-square means of the density parameters
      between quartiles of c-peptide concentration in all breast cancer controls with
      available screening mammography films (n = 1,469). RESULTS: After adjustment for
      adiposity, c-peptide was not associated with any measure of breast density.
      However, c-peptide was associated with an approximately 50% increased risk of
      invasive breast cancer [top vs. bottom quartile, adjusted OR = 1.5, 95%
      confidence interval (CI), 1.1-2.0] that was robust to adjustment for plasma-free
      estradiol and sex hormone-binding globulin. The association was stronger for ER
      negative disease (adjusted OR = 2.0; 95% CI, 1.2-3.6). CONCLUSIONS: Our data
      suggest a positive association between hyperinsulinemia and breast cancer risk
      that occurs through nonestrogenic mechanisms, and that is not mediated by breast
      density. IMPACT: Primary prevention of breast cancer in women with
      hyperinsulinemia may be possible by targeting insulin signaling pathways.

PMID- 24097200
TI  - Recreational physical activity and leisure-time sitting in relation to
      postmenopausal breast cancer risk.
AB  - Epidemiologic evidence supports an inverse association between physical activity
      and postmenopausal breast cancer. Whether associations exist for moderate
      activities, such as walking, and whether associations differ by estrogen receptor
      (ER) status, body mass index (BMI, kg/m(2)), adult weight gain, or use of
      postmenopausal hormones (PMH) is unclear. The relation between time spent sitting
      and breast cancer also is unclear. Among 73,615 postmenopausal women in the
      American Cancer Society Cancer Prevention Study II Nutrition Cohort, 4,760 women
      were diagnosed with breast cancer between 1992 and 2009. Extended Cox regression
      was used to estimate multivariable-adjusted relative risks (RR) of breast cancer
      in relation to total recreational physical activity, walking, and leisure-time
      sitting. Differences in associations by ER status, BMI, weight gain, and PMH use
      were also evaluated. The most active women (those reporting >42 MET-hours/week
      physical activity) experienced 25% lower risk of breast cancer than the least
      active [0-<7 MET-hours/week; 95% confidence interval (CI), 0.63-0.89; Ptrend =
      0.01]. Forty-seven percent of women reported walking as their only recreational
      activity; among these women, a 14% lower risk was observed for >=7 hours/week
      relative to <=3 hours/week of walking (95% CI, 0.75-0.98). Associations did not
      differ by ER status, BMI, weight gain, or PMH use. Sitting time was not
      associated with risk. These results support an inverse association between
      physical activity and postmenopausal breast cancer that does not differ by ER
      status, BMI, weight gain, or PMH use. The finding of a lower risk associated with
      >=7 hours/week of walking may be of public health interest.

PMID- 24097199
TI  - Randomized controlled trial of a sun protection intervention for children of
      melanoma survivors.
AB  - BACKGROUND: We studied whether a melanoma survivor-centered intervention was more
      effective than materials available to the general public in increasing children's
      sun protection. METHODS: In a randomized controlled trial, melanoma survivors (n
      = 340) who had a child <= 12 years received a targeted sun protection
      intervention (DVD and booklets) or standard education. Primary outcomes were
      children's sunburns, children's sun protection, and survivors' psychosocial
      factors at baseline and postintervention (1 and 4 months). RESULTS: The
      intervention increased children's sunscreen reapplication at 1 month (P = 0.002)
      and use of wide-brimmed hats at 4 months (P = 0.045). There were no effects on
      other behaviors or sunburns. The intervention improved survivors' hats/clothing
      self-efficacy at both follow-up assessments (P = 0.026, 0.009). At 4 months, the
      intervention improved survivors' clothing intentions (P = 0.029), knowledge (P =
      0.010), and outcome expectations for hats (P = 0.002) and clothing (P = 0.037).
      Children's sun protection increased with survivors' intervention use. The
      intervention was less effective in survivors who were female or who had a family
      history, older children, or children with higher baseline sun protection scores.
      CONCLUSIONS: A melanoma survivor-centered sun protection intervention can improve
      some child and survivor outcomes. The intervention may be more effective in
      survivors who have younger children or less experience with sun protection.
      Intervention delivery must be enhanced to maximize use. IMPACT: This is the first
      study to examine a sun protection intervention for children of melanoma
      survivors. Findings will guide interventions for this important population at
      increased melanoma risk.

PMID- 24097201
TI  - Serum metabolomic analysis of pancreatic cancer--letter.

PMID- 24097202
TI  - Serum metabolomic analysis of pancreatic cancer--response.

PMID- 24097203
TI  - Long-term statin use and risk of breast cancer--letter.

PMID- 24097204
TI  - Optical systems for point-of-care diagnostic instrumentation: analysis of imaging
      performance and cost.
AB  - One of the key elements in point-of-care (POC) diagnostic test instrumentation is
      the optical system required for signal detection and/or imaging. Many tests which
      use fluorescence, absorbance, or colorimetric optical signals are under
      development for management of infectious diseases in resource limited settings,
      where the overall size and cost of the device is of critical importance. At
      present, high-performance lenses are expensive to fabricate and difficult to
      obtain commercially, presenting barriers for developers of in vitro POC tests or
      microscopic image-based diagnostics. We recently described a compact "hybrid"
      objective lens incorporating both glass and plastic optical elements, with a
      numerical aperture of 1.0 and field-of-view of 250 MUm. This design concept may
      potentially enable mass-production of high-performance, low-cost optical systems
      which can be easily incorporated in the readout path of existing and emerging POC
      diagnostic assays. In this paper, we evaluate the biological imaging performance
      of these lens systems in three broad POC diagnostic application areas; (1) bright
      field microscopy of histopathology slides, (2) cytologic examination of blood
      smears, and (3) immunofluorescence imaging. We also break down the fabrication
      costs and draw comparisons with other miniature optical systems. The hybrid
      lenses provided images with quality comparable to conventional microscopy,
      enabling examination of neoplastic pathology and infectious parasites including
      malaria and cryptosporidium. We describe how these components can be produced at
      below $10 per unit in full-scale production quantities, making these systems well
      suited for use within POC diagnostic instrumentation.

PMID- 24097205
TI  - Recessive spinocerebellar ataxia with paroxysmal cough attacks: a report of five
      cases.
AB  - Hereditary ataxias are a heterogeneous group of neurological diseases
      characterized by progressive cerebellar syndrome and numerous other features,
      which result in great diversity of ataxia subtypes. Despite the characterization
      of a number of both autosomal dominant and autosomal recessive ataxias, it is
      thought that a large group of these conditions remains to be identified. In this
      study, we report the characterization of five patients (three Mexicans and two
      Italians) who exhibit a peculiar form of recessive ataxia associated with
      coughing. The main clinical and neurophysiological features of these patients
      include cerebellar ataxia, paroxysmal cough, restless legs syndrome (RLS),
      choreic movements, atrophy of distal muscles, and oculomotor disorders. Brain
      magnetic resonance imaging (MRI) revealed cerebellar atrophy, while video
      polysomnography (VPSG) studies showed a severe pattern of breathing-related sleep
      disorder, including sleep apnea, snoring, and significant oxygen saturation in
      the absence of risk factors. All patients share clinical features in the
      peripheral nervous system, including reduction of amplitude and prolonged latency
      of sensory potentials in median and sural nerves. Altogether, clinical criteria
      as well as molecular genetic testing that was negative for different autosomal
      dominant and autosomal recessive ataxias suggest the presence of a new form of
      recessive ataxia. This ataxia, in which cerebellar signs are preceded by
      paroxysmal cough, affects not only the cerebellum and its fiber connections, but
      also the sensory peripheral nervous system and extracerebellar central pathways. 

PMID- 24097206
TI  - Platelet-derived microparticle count and surface molecule expression differ
      between subjects with and without type 2 diabetes, independently of obesity
      status.
AB  - This study investigated the impact of either type 2 diabetes or obesity,
      separately or in combination, on the absolute amounts of microparticles (MP) and
      the pathways by which these are associated with either condition. The
      concentrations of circulating MP derived from platelets (PMP), leukocytes (LMP)
      and monocytes (MMP), together with their specific activation markers, were
      compared in 30 subjects who were characterised across 4 cohorts as obese or type
      2 diabetes. The subjects with type 2 diabetes had elevated concentrations of
      total PMP (P = 0.003), and PMP that were fibrinogen-positive (P = 0.04), tissue
      factor-positive (P < 0.001), P-selectin-positive (P = 0.03). Type 2 diabetes did
      not alter either total or activated LMP or MMP. Obesity per se did not impact on
      any MP measurement. Elevated concentrations of plasma PMP occurred in subjects
      with type 2 diabetes, whether they were obese or non-obese. In contrast, obesity
      in the absence of type 2 diabetes had no effect. The increased concentrations of
      specific marker-positive PMP in the subjects with diabetes might reflect
      potential pathways by which PMP may contribute to the pathogenesis of
      atherosclerosis and type 2 diabetes. 

PMID- 24097207
TI  - Vitamin D in "early" primary Sjogren's syndrome: does it play a role in
      influencing disease phenotypes?
AB  - Beyond its well-established role in the maintenance of mineral homeostasis, 25-OH
      vitamin D deficiency seems to be involved in the development and severity of
      several autoimmune diseases. To date, contrasting data have been reported
      regarding the presence of hypovitaminosis D in primary Sjogren's syndrome (pSS).
      To assess the prevalence of hypovitaminosis D in pSS at an early stage of the
      disease and to evaluate its impact on pSS clinical manifestations and disease
      activity, unselected consecutive subjects with recent onset dry mouth and/or dry
      eyes who underwent a comprehensive diagnostic algorithm for pSS (AECG criteria)
      were prospectively included in the study. The levels of 25[OH]-D3 were measured
      by monoclonal antibody immunoradiometric assay. Conditions of 25[OH]-D3 severe
      deficiency, deficiency, and insufficiency were defined as levels <10, <20, and 20
      30 ng/ml, respectively, and their frequencies were investigated in pSS patients
      and controls. The levels of 25[OH]-D3 were also correlated with patients'
      demographic, clinical, and serologic features. Seventy-six consecutive females
      were included: 30/76 patients fulfilled the AECG criteria for pSS. The remaining
      46/76 patients represented the control group. No statistical differences were
      found in the serum levels of 25[OH]-D3 between pSS patients [median levels = 20
      ng/ml (IQR 9.3-26)] and controls [median levels = 22.5 ng/ml (IQR 15.6-33)]. In
      particular, the frequency of 25[OH]-D3 severe deficiency was not significantly
      different in patients with pSS when compared to controls (23 vs. 17.4 %, p value
      = 0.24). We found a significant correlation between serum 25[OH]-D3 levels and
      white blood cells count (r = 0.29, p = 0.01). More specifically, leukocytopenia
      was significantly associated with 25[OH]-D3 severe deficiency, being documented
      in 40 % of the subjects with a 25[OH]-D3 severe deficiency and in 11 % of the
      subjects without a severe vitamin D deficiency (p = 0.02). We did not observe any
      further association or correlation between hypovitaminosis D and pSS glandular
      and extra-glandular features. Although the role of hypovitaminosis D in pSS
      pathogenesis remains controversial, the results of this study encourage the
      assessment of vitamin D in specific pSS subsets that could mostly benefit from a
      supplementation.

PMID- 24097208
TI  - Validation and psychometric properties of the Spanish version of the Quality of
      Life Scale (QOLS) in patients with fibromyalgia.
AB  - Fibromyalgia (FM) is a chronic disease associated with high disability levels,
      which in turn lead to low quality of life (QOL). The objectives of this study
      were to translate the Quality of Life Scale (QOLS) into Spanish and to assess its
      reliability and validity for its use in patients with FM. A total of 140 women
      are suffering from FM (52.87 +/- 9.35 years old). All belonged to an association
      of FM patients (AFIXA, Jaen, Spain). The Spanish versions of the FM impact
      questionnaire (FIQ), the SF-36, and Beck's Depression Inventory were used to
      assess them. The construct's validity was checked by means of exploratory
      factorial analysis (varimax with Kaiser normalization). Test-retest reliability
      was assessed through intraclass correlation coefficient (ICC), and convergent
      validity through Spearman's correlation. Results show that Cronbach's alpha was
      0.887, which revealed high internal consistency. The value of ICC for the QOLS
      total was 0.765 (95 % CI 0.649-0.843, p < 0.001). QOLS presented a significant
      Spearman's correlation (p < 0.01) with Beck's Inventory, with the physical and
      mental subtotals of SF-36 and with FIQ. The main component analysis and the
      varimax rotation revealed the convergence on three factors that account for 54.05
      % of variance. Taking into account the severity of the disorder, significant
      differences (p < 0.05) appeared in QOLS, with moderately afflicted patients
      getting higher scores than the most severe cases. In conclusion, our study shows
      that the Spanish version of the QOLS is a reliable instrument, with a good
      convergent and discriminant construct validity, for measuring the QOL of Spanish
      FM patients.

PMID- 24097209
TI  - Graphene quantum dots as the hole transport layer material for high-performance
      organic solar cells.
AB  - We present an investigation of organic photovoltaic (OPV) cells with solution
      processable graphene quantum dots (GQDs) as hole transport layers (HTLs). GQDs,
      with uniform sizes and good conductivity, are demonstrated to be excellent HTLs
      in both polymer solar cells (PSCs) and small-molecule solar cells (SMSCs) with
      the blend of poly(3-hexylthiophene):[6,6]-phenyl-C61-butyric acid methyl ester
      (P3HT:PC61BM) and small molecule DR3TBDT:[6,6]-phenyl-C71-butyric acid methyl
      ester (DR3TBDT:PC71M) as the active layer, respectively. The PSCs and SMSCs based
      on GQDs yield power conversion efficiencies of 3.51% and 6.82%, respectively,
      both comparable to those of solar cells with PEDOT:PSS as the HTLs. In addition,
      the cells with GQDs as HTLs exhibit much more reproducible performance and longer
      lifetime. In light of the high stability, low cost and easy processing, these
      results indicate that GQDs can be potentially used to replace PEDOT:PSS for
      producing high-performance and stable organic photovoltaic cells. 

PMID- 24097210
TI  - Collective synthesis of several 2,7'-cyclolignans and their correlation by
      chemical transformations.
AB  - Collective synthesis of anti-malarial 2,7'-cyclolignans has been
      stereoselectively achieved employing (+/-)-cyclogalgravin (2) as a linchpin
      through a series of functional group conversions, including redox reactions.
      Interestingly, 2 can be correlated with the neolignan (+/-)-kadangustin J (1)
      isolated from a different plant source, through a highly efficient dehydrative
      cyclization reaction with excellent diastereotopic differentiation of the
      veratryl group and concomitant construction of the C1-C7 bond. It is noteworthy
      that the first total synthesis of stereodivergent (+/-)-8,8'-epi-aristoligone
      (5), (+/-)-8'-epi-aristoligone (7), (+/-)-8'-epi-8-OH-aristoligone (8) and (+/-)
      8'-epi-aristoligol (9) was demonstrated.

PMID- 24097211
TI  - Occurrence of cardiovascular events after the 2011 Great East Japan Earthquake
      and tsunami disaster.
AB  - There are conflicting reports regarding the occurrence of cardiovascular events
      after a major earthquake. To understand the impact of the Great East Japan
      Earthquake on cardiovascular events, we retrospectively examined the clinical
      records prepared by emergency room physicians between 2009 and 2011 (n = 66,244),
      and compared the occurrence of these events between 2011 and 2009, and 2011 and
      2010. There was a significant increase in the number of patients with
      cardiovascular events during the 3 week period after the earthquake in 2011 (n =
      106) compared with that during the same period in 2009 (n = 72) or 2010 (n = 65)
      (P = 0.002). The number of patients with acute coronary syndrome or congestive
      heart failure in March 2011 was significantly increased compared with 2009 or
      2010, however, there were no significant increases in 2011 in other
      cardiovascular events including stroke, aortic dissection, pulmonary
      thromboembolism, or out-of-hospital cardiac arrest compared with 2009 or 2010.
      These findings suggest that the incidence of cardiovascular events may have been
      heterogeneous after the disaster. 

PMID- 24097212
TI  - Effects of ezetimibe on serum polyunsaturated fatty acids in patients with
      coronary artery disease.
AB  - Residual risk of cardiovascular disease might stem, at least partially, from low
      serum concentrations of n-3 polyunsaturated fatty acid (PUFA). The purpose of
      this study was to evaluate the effects of ezetimibe on serum lipids and PU-FAs in
      patients with coronary artery disease who were intolerant of new or high-dose
      statin therapy. The study population consisted of 13 patients who were intolerant
      of new statin therapy and 10 patients who were intolerant of high-dose statin
      therapy for the treatment of low-density lipoprotein (LDL) cholesterol. Patients
      who were intolerant of high-dose statin therapy continued taking a statin, but at
      a lower dose during the study period. Blood samples were collected before and 12
      weeks after ezetimibe (10 mg). We measured serum lipids and PUFAs including
      dihomo-gamma-linolenic acid, arachidonic acid (AA), eicosapentaenoic acid (EPA),
      and docosahexaenoic acid. Ezetimibe significantly decreased LDL cholesterol (138
      +/- 19 mg/dL to 97 +/- 34 mg/dL, P < 0.01), but did not significantly affect high
      density lipoprotein cholesterol, triglyceride, or any of the PUFAs measured
      during the follow-up period. Consequently, it did not affect the ratio of EPA to
      AA (0.40 +/- 0.17 to 0.43 +/- 0.18, P = ns) or the ratio of n-3 PUFA to n-6 PUFA
      (1.10 +/- 0.39 to 1.09 +/- 0.36, P = ns) during the follow-up period. Ezetimibe
      in combination with a low-dose statin, or as monotherapy in statin-intolerant
      patients, decreased LDL cholesterol, but did not significantly affect serum PUFA
      concentrations in patients with coronary artery disease.

PMID- 24097213
TI  - Clinical correlates of insomnia in patients with acute coronary syndrome.
AB  - This study sought to examine the prevalence of insomnia and its association with
      depression, anxiety, and medical comorbidities in patients after an acute
      coronary syndrome (ACS). Insomnia increases risk of recurrent cardiac events in
      ACS patients, but little is known about the prevalence and clinical correlates of
      insomnia in this setting. Patients (n = 102, 58.3 +/- 10.6 years-old) admitted
      for ACS to a cardiology service at an urban academic medical center completed the
      Insomnia Severity Index, Epworth Sleepiness Scale, and measures of depression and
      anxiety. A subset (n = 20) completed ambulatory polysomnography (PSG) in their
      homes several weeks after discharge. Moderate or severe insomnia was reported by
      37% of patients during hospitalization and was associated with 76 minutes more
      wake after sleep onset measured by home PSG. Although depression and insomnia
      were strongly associated, about 1 in 4 patients with insomnia did not report
      significant depressive symptoms. Sleep apnea was documented in 80% of patients on
      PSG, but insomnia was not associated with sleep apnea, periodic limb movements,
      demographic factors, or medical conditions other than liver disease. Insomnia is
      present in over one-third of ACS patients during hospitalization, but at-risk
      patients could not be readily identified by demographic or medical factors or by
      depression symptoms.

PMID- 24097214
TI  - Prediction of coronary artery stenosis at rest in patients with normal left
      ventricular wall motion. Segmental analyses using strain imaging diastolic index.
AB  - Noninvasive detection of coronary artery stenosis usually requires a stress test
      in patients without left ventricular (LV) regional wall motion abnormalities
      (RWMA). In contrast, abnormal regional LV relaxation caused by ischemia may
      persist beyond recovery from transient ischemia. The aim of the present study was
      to determine whether segmental analysis of abnormal regional LV relaxation using
      the strain imaging diastolic index (SI-DI) at rest could predict coronary artery
      stenosis in the three major vessels in patients without LV dysfunction or RWMA.
      We performed 2D speckle tracking echocardiography and coronary angiography in 85
      patients without RWMA with suspected coronary artery disease. Patients with LV
      dysfunction or acute coronary syndrome were excluded. Echocardiographic images of
      the LV were obtained in the apical 2-, 3-, and 4-chamber views and divided into 6
      segments. In each segment, SI-DI derived from transverse strain imaging was
      determined. Forty-eight patients had significant coronary artery stenosis (>=
      70%). The optimal cutoff values of SI-DI were 60.5% in the mid anteroseptal
      segment for detecting left anterior descending artery stenosis (sensitivity,
      83.3%; specificity, 81.1%), 60.5% in the basal anterolateral segment for
      detecting left circumflex artery stenosis (sensitivity, 80.9%; specificity,
      90.3%), and 61.5% in the basal inferior segment for detecting right coronary
      artery stenosis (sensitivity, 74.1%; specificity, 77.8%). A segmental analysis of
      SI-DI at rest predicted coronary artery stenosis in the three major vessels in
      patients without RWMA. This noninvasive method may be useful for detecting
      coronary artery stenosis without a stress test.

PMID- 24097215
TI  - Is visceral fat really a coronary risk factor? A multi-detector computed
      tomography study.
AB  - Metabolic syndrome (MS) is currently considered to be a risk factor for
      arteriosclerotic disease. The accumulation of visceral fat leads to
      arteriosclerotic disease after other risk factors have developed and either
      direct or mutual effects occur. The aim of this study was to verify whether
      visceral fat serves as an independent coronary risk factor. A total of 3157
      patients who had undergone multi-detector computed tomography (MDCT) were
      analyzed via computed tomographic angiography and the measurement of their
      visceral fat area. Coronary arteries with > 70% stenosis were considered to be
      significant. The visceral fat area was measured at the umbilical level, and an
      area of 100 cm2 or more was defined as visceral obesity. Coronary risk factors
      (ie, hypertension, dyslipidemia, diabetes mellitus, family history, and smoking)
      were obtained from the patient medical records. The patients were divided into
      two groups: a visceral obesity group, 1130 patients (137.0 +/- 31.1 cm2) and a
      nonvisceral obesity group, 2027 patients (57.3 +/- 25.8 cm2). A significant
      difference in the incidence of coronary stenosis between the two groups was
      observed. According to multivariable analysis, the factors affecting coronary
      stenosis were age, gender, dyslipidemia, diabetes mellitus, and the ratio of
      visceral to subcutaneous fat. Visceral obesity was not found to be an independent
      coronary risk factor. Visceral obesity demonstrated the predominant presence of
      coronary risk factors.

PMID- 24097216
TI  - Rate-dependent electrophysiologic effects of the class III antiarrhythmic drugs
      nifekalant, amiodarone, and ibutilide on the atrium in patients with persistent
      atrial fibrillation.
AB  - Persistent atrial fibrillation (AF) is characterized by electrical remodeling,
      ie, marked decreases in the atrial effective refractory period (ERP), ERP rate
      adaptation, and atrial conduction velocity. Little information is available on
      the effects of class III antiarrhythmic drugs on the remodeled atrium. We studied
      the effects of the class III antiarrhythmic drugs nifekalant, ibutilide, and
      amiodarone on rate-dependent changes in atrial action potential duration in
      patients with persistent AF. Right atrial (RA) monophasic action potential
      duration (MAPD) and intra-atrial conduction time (IACT) were measured at pacing
      cycle lengths (CLs) of 800, 700, 600, 500, 400, 350, 300, and 250 ms before and
      after administration of nifekalant (0.4 mg/kg + 0.3 mg/kg/hr, iv), amiodarone (5
      mg/kg, iv), or ibutilide (0.01 mg/kg, iv) in 31 patients after successful
      internal cardioversion of chronic AF of > 2 months duration. Nifekalant and
      ibutilide significantly increased RA MAPD and the ERP at each CL in a reverse
      rate-dependent manner. Amiodarone did not affect RA MAPD. Nifekalant did not
      affect IACT, whereas amiodarone increased IACT at each CL in a rate-dependent
      manner, and ibutilide increased IACT at CLs <= 350 ms. The atrial
      electrophysiologic effects of the class III antiarrhythmic drugs nifekalant,
      amiodarone, and ibutilide differ, depending on the degree of electrical and
      structural remodeling and the effects of the drugs on the depolarizing and
      repolarizing currents.

PMID- 24097217
TI  - Three-dimensional high-density bipolar contact mapping of left atrial endocardial
      activation during sinus rhythm in patients with atrial fibrillation.
AB  - Non-contact array mapping studies have demonstrated the existence of a line of
      conduction block along the septopulmonary bundle area and the posterior left
      atrial (LA) roof during sinus rhythm (SR). However, little is known of the global
      LA activation pattern during SR using a high-density contact bipolar mapping
      system. High-density contact bipolar isochronal mapping (bipolar mapping sites:
      292 [IQR 250-348] points) of the LA was performed during SR with the NavX mapping
      system in 20 patients with paroxysmal atrial fibrillation (AF) and 11 patients
      with non-paroxysmal AF. The earliest endocardial breakthrough in the the LA from
      the right atrium (RA) during SR occurred in the anterosuperior LA (77%) or
      anterior to the right pulmonary veins (23%), and the breakthrough site did not
      differ between patients with paroxysmal and non-paroxysmal AF. Regardless of the
      site of breakthrough, the LA activation pattern was homogeneous, and no line of
      functional block was observed in any patient. Total LA activation time was
      significantly longer in non-paroxysmal AF patients than in paroxysmal AF patients
      (95.1 +/- 4.3 ms versus 78.3 +/- 3.2 ms, P = 0.0040). Contact-based bipolar LA
      endocardial activation mapping revealed a homogeneous LA activation pattern
      during SR, regardless of the between-group difference in activation time and the
      between-patient difference in sites of earliest LA endocardial breakthrough from
      the RA.

PMID- 24097218
TI  - Subclinical tonic-clonic epileptic seizure detected by an implantable loop
      recorder.
AB  - A 73-year old man received an implantable loop recorder (ILR) for the evaluation
      of transient loss of consciousness (TLOC) spells. His medical history was without
      any epileptic convulsions or automatism. ILR recording during a spontaneous
      episode revealed the presence of a regular, narrow QRS complex tachycardia
      associated with low-amplitude, high-frequency, continuous or discontinuous
      artifacts, consistent with myopotentials. During the event, the regular, low
      amplitude continuous signals gradually became discontinuous, with a prolongation
      of the inter-signal cycle length, until their disappearance after manual
      activation of the ILR. The patient was diagnosed as experiencing subclinical
      tonic-clonic epileptic seizures. Antiepileptic drug treatment was initiated, and
      the patient has remained free of TLOC symptoms during 13 months follow-up.

PMID- 24097219
TI  - Delayed-onset systolic anterior motion of the mitral valve after aortic valve
      replacement for severe aortic stenosis.
AB  - Systolic anterior motion (SAM) of the mitral valve after aortic valve replacement
      (AVR) for severe aortic stenosis (AS) is one of the causes of perioperative left
      ventricular outflow tract (LVOT) obstruction in older patients. A 90-year-old
      woman underwent AVR with a 19-mm bioprosthesis for symptomatic aortic valve
      stenosis. Preoperative transthoracic echocardiography (TTE) showed left
      ventricular hypertrophy, with LVOT obstruction and mild mitral regurgitation
      (MR). Intraoperative transesophageal echocardiography and postoperative TTE
      showed that the degree of MR was unchanged after surgery. The patient's
      postoperative course was uneventful. However, she developed shortness of breath 6
      months after discharge. A subsequent TTE showed significant LVOT obstruction and
      SAM, which resulted in moderate to severe MR. Because of the patient's advanced
      age, cibenzoline was administered to decrease the left ventricular pressure
      gradient (LVPG) and improve the left ventricular diastolic function. Two months
      after administration of cibenzoline, a TTE showed decreased LVPG, trivial MR, and
      the absence of SAM. This case clearly demonstrated that cibenzoline improved the
      SAM of the mitral valve that arose after AVR for AS in a remote postoperative
      period.

PMID- 24097220
TI  - Epicardial adipose tissue is associated with prevalent atrial fibrillation in
      patients with hypertrophic cardiomyopathy.
AB  - Prevalent atrial fibrillation (AF) in patients with hypertrophic cardiomyopathy
      (HCM) represents an important issue with regard to stroke events caused by
      embolization and is associated with high mortality. Increased epicardial adipose
      tissue (EAT), which shows high metabolic activity, can locally influence the
      activity of the autonomic ganglia, enhancing autonomic dysregulation and
      increasing the likelihood of AF. We tested the hypothesis that EAT is associated
      with prevalent AF in HCM patients. Sixty-two patients with idiopathic HCM
      diagnosed on the basis of ultrasound cardiography findings and histopathological
      evaluation of myocardium obtained by right ventricular biopsy underwent cardiac
      magnetic resonance imaging to estimate the extent of EAT. EAT area was
      significantly higher in the group with AF episodes than in the group without. An
      increased incidence of AF was found to be significantly related to an increase in
      EAT, and this association persisted after adjustment for body mass index, sex,
      and age. Time domain measures of heart rate variability measured by Holter
      electrocardiography, standard deviation of normal to normal, and standard
      deviation of the average of normal to normal were negatively related to EAT area.
      EAT was positively correlated with intraventricular septal thickness and cystatin
      C level and negatively correlated with the 24-hour creatinine clearance rate.
      Increased EAT area in HCM patients is significantly related to the presence of
      AF, which is associated with changes in baseline autonomic nervous tone, left
      ventricular mass, and chronic kidney disease.

PMID- 24097222
TI  - Distinct prognostic factors in patients with chronic heart failure and chronic
      kidney disease.
AB  - Impaired renal function is a strong predictor of mortality in chronic heart
      failure (CHF). However, the impact of chronic kidney disease (CKD) on prognostic
      factors has not been rigorously examined in CHF. The purpose of this study was to
      compare prognostic factors between CHF patients with and without CKD. Consecutive
      505 patients with CHF, who performed cardiopulmonary exercise testing before
      discharge, were enrolled. Patients were divided into two groups: CKD group (eGFR
      < 60 mL/minute/1.73 m2, n = 213) and non-CKD group (eGFR >= 60 mL/minute/1.73 m2,
      n = 292). The patients were followed up to register cardiac events including
      cardiac death and re-hospitalization due to worsening heart failure. There were
      115 events during the follow-up period (746 +/- 238 days), and the cardiac event
      rate was higher in the CKD group than in the non-CKD group (34% versus 14%, P <
      0.001). Multivariate Cox hazard analysis demonstrated that body mass index (P <
      0.001), log BNP (P < 0.001), peak VO2 (P < 0.05), and left atrial dimension (P <
      0.05) were independent parameters to predict cardiac events after discharge in
      the non-CKD group. In contrast, peak VO2 (P < 0.01), log BNP (P < 0.01), and the
      concentrations of hemoglobin (P < 0.05) and uric acid (P < 0.05) were independent
      prognostic factors in the CKD group. Prognostic factors were different between
      CHF patients with and without CKD, and this should be considered when managing
      CHF patients with CKD.

PMID- 24097221
TI  - Influence of renal dysfunction on clinical outcomes in patients with congestive
      heart failure complicating acute myocardial infarction.
AB  - The clinical course and medical treatment of patients with congestive heart
      failure (CHF) complicating acute myocardial infarction (AMI) are not well
      established, especially in patients with concomitant renal dysfunction. We
      performed a retrospective analysis of the prospective Korean Acute Myocardial
      Infarction Registry to assess the medical treatments and clinical outcomes of
      patients with CHF (Killip classes II or III) complicated by AMI, in the presence
      or absence of renal dysfunction. Of 13,498 patients with AMI, 2769 (20.5%) had
      CHF on admission. Compared to CHF patients with preserved renal function, in
      hospital mortality and major adverse cardiac events were increased both at 1
      month and at 1 year after discharge in patients with renal dysfunction (1154;
      41.7%). Postdischarge use of aspirin, betablockers, calcium channel blockers,
      angiotensin-converting enzyme inhibitors, or angiotensin II receptor blockers and
      statins significantly reduced the 1-year mortality rate for CHF patients with
      renal dysfunction; such reduction was not observed for those without renal
      dysfunction, except in the case of aspirin. Patients with CHF complicating AMI,
      which is accompanied by renal dysfunction, are at higher risk for adverse
      cardiovascular outcomes than patients without renal dysfunction. However, they
      receive fewer medications proven to reduce mortality rates. 

PMID- 24097223
TI  - Ejection Fraction and ESPVR. A study from a theoretical perspective.
AB  - A formula derived by using large elastic deformation for the contraction of the
      myocardium is used to describe the pressure-volume relation (PVR) in the heart
      left ventricle, it is also used to calculate a mathematical expression for the
      non-linear end-systolic pressure-volume relation (ESPVR) in the left ventricle.
      An important feature of the mathematical formalism used is the inclusion of the
      isovolumic pressure Piso (equal active pressure generated by the myocardium) in
      the formalism describing the PVR. Relations between the ejection fraction (EF)
      and parameters describing the non-linear ESPVR are presented. It is shown that
      the non-linear ESPVR offers a rich collection of parameters that can be used to
      study the performance of the ventricles, like the areas under the ESPVR (units of
      energy) or the ordinates of the ESPVR (units of pressure), slopes and intercepts
      of the curves involved. The mathematical procedure can be easily implemented in a
      non-invasive way in routine clinical work when ratios of variables are
      calculated, it necessitates only the non-invasive measurement of the dimensions
      of the ventricles. Applications to clinical data published in the literature are
      presented, and they give results that show the consistency of the mathematical
      formalism used. The implications of the results of this research work on the
      study of the problem of heart failure with normal or preserved ejection fraction
      (HFpEF) are discussed.

PMID- 24097224
TI  - Successful treatment of hemodynamic compromise caused by antibody-mediated and
      cellular rejection in a recipient 12 years after heart transplantation.
AB  - Heart transplantation (HTx) is an established therapy for stage D heart failure
      due to recent advances in immunosuppressive regimens. However, antibody-mediated
      rejection remains an unsolved problem because of its refractoriness to standard
      immunosuppressive therapy with high mortality and graft loss. We experienced a 16
      year old patient with hemodynamic compromise caused by both cellular and antibody
      mediated rejection 12 years after HTx. The rejection was refractory to repeated
      steroid pulse treatment, intravenous immunoglobulin administration, and
      intensifying immunosuppression including addition of everolimus. Eventually, she
      was successfully treated with repeated plasma exchange accompanied by a single
      administration of the anti-CD20 monoclonal antibody rituximab.

PMID- 24097225
TI  - Optical coherence tomographic and angioscopic assessments of arterial healing in
      coronary artery perforation after implantation of zotarolimus-eluting stent.
AB  - We report the case of a 69-year-old male whose left circumflex coronary artery
      was perforated immediately after implantation of an Endeavor zotarolimus-eluting
      stent (E-ZES). Despite successful hemostasis by long balloon inflation, a
      coronary pseudoaneurysm remained at the E-ZES-implanted segment. Coronary
      angiography performed one year after the coronary perforation showed the
      pseudoaneurysm had disappeared. Simultaneous optical coherence tomography and
      coronary angioscopy revealed that stent struts of the E-ZES were fully covered
      with thick neointima. This is the first case report of a relatively rapid healing
      process for an E-ZES-related coronary pseudoaneurysm.

PMID- 24097226
TI  - Femoral vein thrombosis after right-sided electrophysiological procedures.
AB  - PURPOSE: Electrophysiological studies and radiofrequency catheter ablations
      require single or multiple sheath placements through femoral vein cannulation.
      The objective of this study was to determine the incidence, predictors, and
      outcomes of deep vein thrombosis (DVT) following such procedures. METHODS AND
      RESULTS: We prospectively enrolled 220 consecutive patients with a median age of
      70 [60-79] years. The median duration of the procedures from insertion to removal
      of sheaths was 45 [30-75] min. At least two sheaths were inserted in 158 (72%) of
      the cases. Duplex ultrasonography evaluation of the lower leg veins was performed
      6 h after the procedure and revealed common femoral vein thrombosis in 11 (5%)
      patients. All thrombi were partial and none was complete. Thrombi were mobile in
      four patients and extended to the external iliac vein in three patients. None of
      the patients presented with clinical signs of DVT or pulmonary embolism.
      Anticoagulation was prescribed for 2-4 weeks and a follow-up duplex
      ultrasonography obtained in the first seven patients revealed complete resolution
      of thrombi in all cases. On multivariate analysis, two predictors of thrombosis
      occurrence were identified: a greater sum of sheath diameters (odds ratio, 1.41
      [95% confidence interval, 1.25-1.60] per 1-French increase; p < 0.001) and a
      longer procedural duration (odds ratio, 1.02 [95% confidence interval, 1.00-1.04]
      per 1-min increase; p = 0.04). CONCLUSIONS: Asymptomatic femoral DVT occur in 5%
      of electrophysiological studies and right-heart radiofrequency catheter
      ablations, particularly when large sheaths are inserted for a longer period. The
      role of anticoagulation in this clinical setting warrants further evaluation.

PMID- 24097227
TI  - Increased prevalence of circulating novel IL-17 secreting Foxp3 expressing CD4+ T
      cells and defective suppressive function of circulating Foxp3+ regulatory cells
      support plasticity between Th17 and regulatory T cells in inflammatory bowel
      disease patients.
AB  - BACKGROUND: IL-17 and Foxp3 double-expressing (DE) CD4(+) T lymphocytes are novel
      crossover immune cell population, but the presence and role of these cells in
      human intestinal inflammation is unclear. The aim of this study was to
      investigate the circulating IL-17 and Foxp3 DE CD4(+) T lymphocytes in patients
      with inflammatory bowel disease (IBD). METHODS: The entire cohort consisted of 79
      subjects: 31 patients with Crohn's disease, 28 patients with ulcerative colitis,
      and 20 healthy control subjects (HC). IBD patients with evidence of active
      disease at endoscopy were entered into the study. Peripheral blood mononuclear
      cells were used for ex vivo and in vitro studies to assess the characteristics
      and generation of these novel cells and the function of circulating Foxp3 CD4(+)
      regulatory T lymphocytes (Treg) in patients with IBD compared with HC. RESULTS:
      Patients with IBD had significantly higher prevalence of IL-17 and Foxp3 DE
      CD4(+) T lymphocytes compared with age- and gender-matched HC. These cells
      expressed RORgammat. The ability of Treg cells to suppress autologous T-cell
      proliferation was reduced by approximately 60% in patients with IBD compared with
      HC. Increased generation of these DE cells was demonstrated by the modulation of
      cytokine environment of CD4(+) lymphocytes in vitro in patients with Crohn's
      disease. CONCLUSIONS: Prevalence of circulating IL-17 and Foxp3 DE CD4(+) T cells
      is increased in patients with IBD. Coexpression of RORgammat and Foxp3 in these
      cells implies conversion from Treg cells to Th17 cells. This is associated with a
      decreased suppressive function of Foxp3 CD4(+) T lymphocytes in patients with
      IBD.

PMID- 24097228
TI  - Clonal expansions and short telomeres are associated with neoplasia in early
      onset, but not late-onset, ulcerative colitis.
AB  - BACKGROUND: Patients with ulcerative colitis (UC) are at risk of developing
      colorectal cancer. We have previously reported that cancer progression is
      associated with the presence of clonal expansions and shorter telomeres in
      nondysplastic mucosa. We sought to validate these findings in an independent case
      control study. METHODS: This study included 33 patients with UC: 14 progressors
      (patients with high-grade dysplasia or cancer) and 19 nonprogressors. For each
      patient, a mean of 5 nondysplastic biopsies from proximal, mid, and distal colon
      were assessed for clonal expansions, as determined by clonal length altering
      mutations in polyguanine tracts, and telomere length, as measured by quantitative
      PCR. Both parameters were compared with individual clinicopathological
      characteristics. RESULTS: Clonal expansions and shorter telomeres were more
      frequent in nondysplastic biopsies from UC progressors than nonprogressors, but
      only for patients with early-onset of UC (diagnosis at younger than 50 years of
      age). Late-onset progressor patients had very few or no clonal expansions and
      longer telomeres. A few nonprogressors exhibited clonal expansions, which were
      associated with older age and shorter telomeres. In progressors, clonal
      expansions were associated with proximity to dysplasia. The mean percentage of
      clonally expanded mutations distinguished early-onset progressors from
      nonprogressors with 100% sensitivity and 80% specificity. CONCLUSIONS: Early
      onset progressors develop cancer in a field of clonally expanded epithelium with
      shorter telomeres. The detection of these clones in a few random nondysplastic
      colon biopsies is a promising cancer biomarker in early-onset UC. Curiously,
      patients with late-onset UC seem to develop cancer without the involvement of
      such fields.

PMID- 24097230
TI  - Anterior corpectomy versus posterior laminoplasty for multilevel cervical
      myelopathy: a systematic review and meta-analysis.
AB  - BACKGROUND: Surgical strategy for multilevel cervical myelopathy resulting from
      cervical spondylotic myelopathy (CSM) or ossification of posterior longitudinal
      ligament (OPLL) still remains controversial. There are still questions about the
      relative benefit and safety of direct decompression by anterior corpectomy (CORP)
      versus indirect decompression by posterior laminoplasty (LAMP). OBJECTIVE: To
      perform a systematic review and meta-analysis evaluating the results of anterior
      CORP compared with posterior LAMP for patients with multilevel cervical
      myelopathy. METHODS: Systematic review and meta-analysis of cohort studies
      comparing anterior CORP with posterior LAMP for the treatment of multilevel
      cervical myelopathy due to CSM or OPLL from 1990 to December 2012. An extensive
      search of literature was performed in Pubmed, Embase, and the Cochrane library.
      The quality of the studies was assessed according to GRADE. The following outcome
      measures were extracted: pre- and postoperative Japanese orthopedic association
      (JOA) score, neurological recovery rate (RR), surgical complications, reoperation
      rate, operation time and blood loss. Two reviewers independently assessed each
      study for quality and extracted data. Subgroup analysis was conducted according
      to the mean number of surgical segments. RESULTS: A total of 12 studies were
      included in this review, all of which were prospective or retrospective cohort
      studies with relatively low quality. The results indicated that the mean JOA
      score system for cervical myelopathy and the neurological RR in the CORP group
      were superior to those in the LAMP group when the mean surgical segments were <3,
      but were similar between the two groups in the case of the mean surgical segments
      equal to 3 or more. There was no statistical difference in the surgical
      complication rate between the two groups when the mean surgical segments <3, but
      were significantly higher incidences of surgical complications and complication
      related reoperation in the CORP group compared with the LAMP group in the case of
      the mean surgical segments equal to 3 or more. Besides, the operation time in the
      CORP group was longer than that in the LAMP group, and the average blood loss was
      significantly more in the CORP group compared with the LAMP group. CONCLUSION:
      Based on the results above, anterior CORP and fusion is recommended for the
      treatment of multilevel cervical myelopathy when the involved surgical segments
      were <3. Given the higher rates of surgical complications and complication
      related reoperation and the higher surgical trauma associated with multilevel
      CORP, however, it is suggested that posterior LAMP may be the preferred method of
      treatment for multilevel cervical myelopathy when the involved surgical segments
      were equal to 3 or more. In addition, taking the limitations of this study into
      consideration, it was still not appropriate to draw a strong conclusion claiming
      superiority for CORP or LAMP. A well-designed, prospective, randomized controlled
      trial is necessary to provide objective data on the clinical results of both
      procedures.

PMID- 24097231
TI  - Circumspinal decompression and fusion through a posterior midline incision to
      treat central calcified thoracolumbar disc herniation: a minimal 2-year follow-up
      study with reconstruction CT.
AB  - PURPOSE: There have been several surgical approaches used in the treatment of
      thoracolumbar disc herniation (TLDH) from T10/11 to L1/2. However, central
      calcified TLDH cases are still challenging to spine surgeons. The anterior
      transthoracic approaches and lateral/posterolateral approaches are all
      essentially performed from one side; thus, the compressive lesion and the dura
      matter on the other side of the spinal canal are not clearly visualized,
      predisposing the procedure to incomplete decompression or inadvertent cord
      manipulation. Moreover, a number of these approaches are technically demanding
      and require entry into the chest. The purpose of this study was to introduce a
      new surgical procedure-circumspinal decompression and fusion through a posterior
      midline incision-for the treatment of central calcified TLDH and to evaluate its
      surgical outcome. METHODS: In this study, 22 patients (15 males and 7 females;
      mean age 49 years) with central calcified TLDH underwent this procedure between
      April 2008 and April 2011. Altogether, 26 discs were excised, with two discs at
      T10/11, eight discs at T11/12, nine discs at T12/L1 and seven discs at L1/2. Of
      these patients, 16 returned for final follow-up, with a mean follow-up period of
      41 months (range 24-57 months). Clinical outcomes, including operative time,
      blood loss, perioperative complications, post-operative time of hospitalization,
      neurological status improvement, extent of decompression, back pain, local spinal
      curvature and fusion, were investigated. The patients' neurological status was
      evaluated by a modified Japanese Orthopedic Association scoring system of 11
      points. Fusion and the extent of decompression were evaluated by reconstruction
      CT at final follow-up. RESULTS: The mean operative time was 185 min, the mean
      blood loss was 896 ml and the mean post-operative hospitalization time was 8
      days. Four patients suffered perioperative complications, but only two were
      related to dura violation and none involved the respiratory system. All of the 16
      patients who returned for the final follow-up showed improvement, and evidence of
      improvement was found in five of the other six patients who did not return for
      final follow-up through telephone interview or earlier follow-up evaluations.
      Complete decompression was achieved in 12 of the 16 patients who returned for
      final follow-up. In the 16 patients who returned for final follow-up, back pain
      was significantly reduced and local spinal curvature remained unaltered. In
      addition, based on reconstruction CT images, solid fusion was observed in 15 of
      the 16 patients who returned for final follow-up. CONCLUSIONS: The circumspinal
      decompression and fusion through a posterior midline incision procedure can be
      used to treat central calcified TLDH patients with neurological deficits. This
      method's greatest advantage is that it is a highly effective and safe procedure
      for decompression. Although it is a major and destructive procedure, spinal
      stability was well maintained in most of the cases. In this era when minimally
      invasive spine surgeries like thoracoscopy have been in an upward trajectory,
      spine surgeons still should be made aware of this procedure.

PMID- 24097229
TI  - Physiology and pathophysiology of SLC12A1/2 transporters.
AB  - The electroneutral Na(+)-K(+)-Cl(-) cotransporters NKCC1 (encoded by the SLC12A2
      gene) and NKCC2 (SLC12A1 gene) belong to the Na(+)-dependent subgroup of solute
      carrier 12 (SLC12) family of transporters. They mediate the electroneutral
      movement of Na(+) and K(+), tightly coupled to the movement of Cl(-) across cell
      membranes. As they use the energy of the ion gradients generated by the
      Na(+)/K(+)-ATPase to transport Na(+), K(+), and Cl(-) from the outside to the
      inside of a cell, they are considered secondary active transport mechanisms. NKCC
      mediated transport occurs in a 1Na(+), 1K(+), and 2Cl(-) ratio, although NKCC1
      has been shown to sometimes mediate partial reactions. Both transporters are
      blocked by bumetanide and furosemide, drugs which are commonly used in clinical
      medicine. NKCC2 is the molecular target of loop diuretics as it is expressed on
      the apical membrane of thick ascending limb of Henle epithelial cells, where it
      mediates NaCl reabsorption. NKCC1, in contrast, is found on the basolateral
      membrane of Cl(-) secretory epithelial cells, as well as in a variety of non
      epithelial cells, where it mediates cell volume regulation and participates in
      Cl(-) homeostasis. Following their molecular identification two decades ago, much
      has been learned about their biophysical properties, their mode of operation,
      their regulation by kinases and phosphatases, and their physiological relevance.
      However, despite this tremendous amount of new information, there are still so
      many gaps in our knowledge. This review summarizes information that constitutes
      consensus in the field, but it also discusses current points of controversy and
      highlights many unanswered questions. 

PMID- 24097232
TI  - Reconstruction using a frozen tumor-bearing vertebra in total en bloc
      spondylectomy can enhance antitumor immunity.
AB  - PURPOSE: Distant metastases from thyroid carcinoma are successfully cured if they
      take up radioiodine ((131)I), are of small size, and located in the lungs. Bone
      metastases have the worst prognosis because (131)I therapy and external beam
      radiotherapy are less effective. Our propose here is to report a patient with
      solitary spinal metastasis and multiple lung metastases from thyroid carcinoma,
      whose spinal metastasis was treated by total en bloc spondylectomy (TES)
      enhancing antitumor immunity using frozen tumor-bearing bone for spinal
      reconstruction. METHODS: The patient was a 37-year-old male who had solitary
      spinal metastasis at T4 and multiple lung metastases from thyroid carcinoma.
      (131)I therapy for the multiple lung metastases resulted in no effect because the
      apparent (131)I uptake was observed only in T4 metastasis. We performed a TES of
      T4 with cryotreatment. After en bloc excision of T4, the excised tumor-bearing
      vertebra was frozen by liquid nitrogen. In spinal reconstruction, the frozen
      vertebra was used in a mesh cage inserted into the anterior defect. RESULTS:
      After surgery, the thyroglobulin level decreased without any other adjuvant
      therapy and the serum levels of INF-gamma and IL-12 increased. This indicates
      antitumor immunity was activated. Then, (131)I therapy became effective to the
      lung metastases causing the tumors to decrease in size and number. Three years
      after surgery, progression in the lung metastases, other metastasis, and local
      recurrence have not been observed. CONCLUSIONS: TES with cryotreatment as
      presented is a novel surgery which can enhance antitumor immunity against other
      visible or non-visible metastases.

PMID- 24097233
TI  - Development of a multiplex sandwich aptamer microarray for the detection of
      VEGF165 and thrombin.
AB  - In this work we have developed a multiplex microarray system capable of detecting
      VEGF165 and thrombin. We recently described a Sandwich Aptamer Microarray (SAM)
      for thrombin detection feasible for use in multiplex microarrays; here we
      describe a new aptasensor for VEGF165 detection employing Vap7 and VEa5, two DNA
      aptamers recognizing different sites of the protein. The aptamers were modified
      to be adapted to the solid phase platform of SAM and their capability to
      simultaneously recognize VEGF165 by forming a ternary complex was analyzed in
      solution. Having so defined the best tandem arrangement of modified aptamers, we
      set up the aptasensor for VEGF165, and finally analyzed the multiplex system with
      the two aptasensors for the simultaneous detection of VEGF165 and thrombin. The
      results indicate that each sandwich is specific, even when the two proteins are
      mixed. The system performance is consistent with the behavior evidenced by the
      biochemical analysis, which proves to be valuable to drive the evaluation and
      refinement of aptamers prior to or along the development of a detection platform.
      Since thrombin upregulates VEGF expression, the simultaneous recognition of these
      two proteins could be useful in the analysis of biomarkers in pathologies
      characterized by neo-angiogenesis. 

PMID- 24097235
TI  - Snapshots of non-equilibrium Dirac carrier distributions in graphene.
AB  - The optical properties of graphene are made unique by the linear band structure
      and the vanishing density of states at the Dirac point. It has been proposed that
      even in the absence of a bandgap, a relaxation bottleneck at the Dirac point may
      allow for population inversion and lasing at arbitrarily long wavelengths.
      Furthermore, efficient carrier multiplication by impact ionization has been
      discussed in the context of light harvesting applications. However, all of these
      effects are difficult to test quantitatively by measuring the transient optical
      properties alone, as these only indirectly reflect the energy- and momentum
      dependent carrier distributions. Here, we use time- and angle-resolved
      photoemission spectroscopy with femtosecond extreme-ultraviolet pulses to
      directly probe the non-equilibrium response of Dirac electrons near the K-point
      of the Brillouin zone. In lightly hole-doped epitaxial graphene samples, we
      explore excitation in the mid- and near-infrared, both below and above the
      minimum photon energy for direct interband transitions. Whereas excitation in the
      mid-infrared results only in heating of the equilibrium carrier distribution,
      interband excitations give rise to population inversion, suggesting that
      terahertz lasing may be possible. However, in neither excitation regime do we
      find any indication of carrier multiplication, questioning the applicability of
      graphene for light harvesting. 

PMID- 24097236
TI  - [Hand surgery. Surgery in rhizarthrosis: prospective comparison].

PMID- 24097237
TI  - [How can we improve patient safety?].

PMID- 24097234
TI  - Universal glove and gown use and acquisition of antibiotic-resistant bacteria in
      the ICU: a randomized trial.
AB  - IMPORTANCE: Antibiotic-resistant bacteria are associated with increased patient
      morbidity and mortality. It is unknown whether wearing gloves and gowns for all
      patient contact in the intensive care unit (ICU) decreases acquisition of
      antibiotic-resistant bacteria. OBJECTIVE: To assess whether wearing gloves and
      gowns for all patient contact in the ICU decreases acquisition of methicillin
      resistant Staphylococcus aureus (MRSA) or vancomycin-resistant Enterococcus (VRE)
      compared with usual care. DESIGN, SETTING, AND PARTICIPANTS: Cluster-randomized
      trial in 20 medical and surgical ICUs in 20 US hospitals from January 4, 2012, to
      October 4, 2012. INTERVENTIONS: In the intervention ICUs, all health care workers
      were required to wear gloves and gowns for all patient contact and when entering
      any patient room. MAIN OUTCOMES AND MEASURES: The primary outcome was acquisition
      of MRSA or VRE based on surveillance cultures collected on admission and
      discharge from the ICU. Secondary outcomes included individual VRE acquisition,
      MRSA acquisition, frequency of health care worker visits, hand hygiene
      compliance, health care-associated infections, and adverse events. RESULTS: From
      the 26,180 patients included, 92,241 swabs were collected for the primary
      outcome. Intervention ICUs had a decrease in the primary outcome of MRSA or VRE
      from 21.35 acquisitions per 1000 patient-days (95% CI, 17.57 to 25.94) in the
      baseline period to 16.91 acquisitions per 1000 patient-days (95% CI, 14.09 to
      20.28) in the study period, whereas control ICUs had a decrease in MRSA or VRE
      from 19.02 acquisitions per 1000 patient-days (95% CI, 14.20 to 25.49) in the
      baseline period to 16.29 acquisitions per 1000 patient-days (95% CI, 13.48 to
      19.68) in the study period, a difference in changes that was not statistically
      significant (difference, -1.71 acquisitions per 1000 person-days, 95% CI, -6.15
      to 2.73; P = .57). For key secondary outcomes, there was no difference in VRE
      acquisition with the intervention (difference,  0.89 acquisitions per 1000 person
      days; 95% CI, -4.27 to 6.04, P = .70), whereas for MRSA, there were fewer
      acquisitions with the intervention (difference, -2.98 acquisitions per 1000
      person-days; 95% CI, -5.58 to -0.38; P = .046). Universal glove and gown use also
      decreased health care worker room entry (4.28 vs 5.24 entries per hour,
      difference, -0.96; 95% CI, -1.71 to -0.21, P = .02), increased room-exit hand
      hygiene compliance (78.3% vs 62.9%, difference, 15.4%; 95% CI, 8.99% to 21.8%; P
      = .02) and had no statistically significant effect on rates of adverse events
      (58.7 events per 1000 patient days vs 74.4 events per 1000 patient days;
      difference, -15.7; 95% CI, -40.7 to 9.2, P = .24). CONCLUSIONS AND RELEVANCE: The
      use of gloves and gowns for all patient contact compared with usual care among
      patients in medical and surgical ICUs did not result in a difference in the
      primary outcome of acquisition of MRSA or VRE. Although there was a lower risk of
      MRSA acquisition alone and no difference in adverse events, these secondary
      outcomes require replication before reaching definitive conclusions. TRIAL
      REGISTRATION: clinicaltrials.gov Identifier: NCT0131821.

PMID- 24097238
TI  - [Patient safety in health service research].
AB  - Patient safety is an essential quality criterion for good medical care. A main
      aim of patient safety interventions is the prevention and/or reduction of adverse
      events. Various approaches are available for this. The multidisciplinarity in
      health services research as well as the wide range of methods and topics leads to
      the fact that health services research is predestined to deal with many of the
      resulting research questions and with respect to the complexity. 

PMID- 24097239
TI  - [What is the meaning of safety in hospitals?].
AB  - Patient safety in hospitals is difficult to define and is not measurable by
      operational safety parameters as in other fields. So-called adverse events (AE)
      are a collective of complications, failures, mistakes, errors and violations.
      Estimations of at least 9.2 % AEs in surgery with 0.1 % fatalities are given
      worldwide but there are no correlations between objective quantification of AEs
      and subjective or public perception of safety during the perioperative period.
      Patient safety during this period is mostly endangered by wound infections
      (safety 98 %) and nosocomial infections (safety 97 %). In spite of these facts,
      safety parameters for problems in anesthesia, blood transfusion, in retaining
      surgical instruments and so-called index events, such as patient and side
      identification errors are much higher. Patient safety is maintained in hospitals
      by objective means (surgical). Checklists have been proven to improve safety and
      critical incidence reporting, training and changing of attitudes could have
      further advantages but they are difficult to measure. 

PMID- 24097240
TI  - [Human factors and crisis resource management: improving patient safety].
AB  - A continuing high number of patients suffer harm from medical treatment. In 60
      70% of the cases the sources of harm can be attributed to the field of human
      factors (HFs) and teamwork; nevertheless, those topics are still neither part of
      medical education nor of basic and advanced training even though it has been
      known for many years and it has meanwhile also been demonstrated for surgical
      specialties that training in human factors and teamwork considerably reduces
      surgical mortality.Besides the medical field, the concept of crisis resource
      management (CRM) has already proven its worth in many other industries by
      improving teamwork and reducing errors in the domain of human factors. One of the
      best ways to learn about CRM and HFs is realistic simulation team training with
      well-trained instructors in CRM and HF. The educational concept of the HOTT (hand
      over team training) courses for trauma room training offered by the DGU
      integrates these elements based on the current state of science. It is time to
      establish such training for all medical teams in emergency medicine and operative
      care. Accompanying safety measures, such as the development of a positive culture
      of safety in every department and the use of effective critical incident
      reporting systems (CIRs) should be pursued. 

PMID- 24097241
TI  - [Does simulator-based team training improve patient safety?].
AB  - Patient safety became paramount in medicine as well as in emergency medicine
      after it was recognized that preventable, adverse events significantly
      contributed to morbidity and mortality during hospital stay. The underlying
      errors cannot usually be explained by medical technical inadequacies only but are
      more due to difficulties in the transition of theoretical knowledge into tasks
      under the conditions of clinical reality. Crew Resource Management and Human
      Factors which determine safety and efficiency of humans in complex situations are
      suitable to control such sources of error. Simulation significantly improved
      safety in high reliability organizations, such as the aerospace industry.Thus,
      simulator-based team training has also been proposed for medical areas. As such
      training is consuming in cost, time and human resources, the question of the cost
      benefit ratio obviously arises. This review outlines the effects of simulator
      based team training on patient safety. Such course formats are not only capable
      of creating awareness and improvements in safety culture but also improve
      technical team performance and emphasize team performance as a clinical
      competence. A few studies even indicated improvement of patient-centered outcome,
      such as a reduced rate of adverse events but further studies are required in this
      respect. In summary, simulator-based team training should be accepted as a
      suitable strategy to improve patient safety. 

PMID- 24097242
TI  - [Pain therapy options in trauma and emergency surgery].
AB  - Sufficient acute pain therapy has been scientifically proven to be one of the
      therapeutic pillars for rapid patient convalescence, a low rate of pain
      chronification, and a high grade of patient satisfaction. This includes not only
      systemic pharmacological pain therapy, but also nonpharmaceutical measures, e.g.,
      physical, psychological, locoregional, and adequate patient information. This
      requires a specific infrastructure, exact clinical control mechanisms, and
      fundamental knowledge about pain avoidance. The surgeon can responsibly
      contribute to this. The goal of the following article is to demonstrate and
      deepen this knowledge and to describe the newest scientific developments. 

PMID- 24097245
TI  - Structural, Electronic and Charge Transfer Studies of Highly Sensitive
      Fluorescent Probe 2-((E)-2-(1-phenyl-1H-phenanthro[9,10-d]imidazol-2
      yl)vinyl)phenol: Quantum Chemical Investigations.
AB  - This article presents a facile synthesis of novel class of bluish-green
      fluorescent 2-((E)-2-(1-phenyl-1H-phenanthro[9,10-d]imidazol-2-yl)vinyl)phenol
      [PPIVP] and their optical, electrochemical and thermal properties. Detailed
      photophysical and quantum chemical studies have been performed to elucidate the
      origin of the dual emission shifts. PPIVP undergo excited state intramolecular
      proton transfer (ESIPT) reaction leading a large Stoke's shifted fluorescence
      emission from the phototautomer. The results of quantum chemical investigations
      not only confirmed the intramolecular charge transfer characteristics of the
      ESIPT tautomers but also provided a rational for the observed high fluorescence
      quantum efficiency in the solid state. The high photoluminescence quantum yield
      in the solid state is ascribed to twisted chromophores due to phenyl substituents
      at 1,2-position of the phenanthroimidazole ring which restricted intramolecular
      motion, leading to an optically allowed lowest optical transition without self
      quenching. 

PMID- 24097244
TI  - The CBL-CIPK network mediates different signaling pathways in plants.
AB  - The calcineurin B-like protein-CBL-interacting protein kinase (CBL-CIPK)
      signaling pathway in plants is a Ca2+-related pathway that responds strongly to
      both abiotic and biotic environmental stimuli. The CBL-CIPK system shows variety,
      specificity, and complexity in response to different stresses, and the CBL-CIPK
      signaling pathway is regulated by complex mechanisms in plant cells. As a plant
      specific Ca2+ sensor relaying pathway, the CBL-CIPK pathway has some crosstalk
      with other signaling pathways. In addition, research has shown that there is
      crosstalk between the CBL-CIPK pathway and the low-K+ response pathway, the ABA
      signaling pathway, the nitrate sensing and signaling pathway, and others. In this
      paper, we summarize and review research discoveries on the CBL-CIPK network. We
      focus on the different modification and regulation mechanisms (phosphorylation
      and dephosphorylation, dual lipid modification) of the CBL-CIPK network, the
      expression patterns and functions of CBL-CIPK network genes, the responses of
      this network to abiotic stresses, and its crosstalk with other signaling
      pathways. We also discuss the technical research methods used to analyze the CBL
      CIPK network and some of its newly discovered functions in plants.

PMID- 24097246
TI  - Contribution of family labour to the profitability and competitiveness of small
      scale dairy production systems in central Mexico.
AB  - The objective of this work was to determine the effect of family labour on the
      profitability and competitiveness of small-scale dairy farms in the highlands of
      Central Mexico. Economic data from 37 farms were analysed from a stratified
      statistical sampling with a Neyman assignment. Three strata were defined taking
      herd size as criterion. Stratum 1: herds from 3 to 9 cows plus replacements,
      Stratum 2: herds from 10 to 19 cows and Stratum 3: herds from 20 to 30 cows. The
      policy analysis matrix was used as the method to determine profitability and
      competitiveness. The coefficient of private profitability (CPP) when the economic
      cost of family labour is included in the cost structure was 8.0 %, 31.0 % and
      46.0 %. When the economic cost of family labour is not included, CPP increase to
      47.0 %, 57.0 % and 66.0 % for each strata, respectively. The private cost ratio
      (PCR) when family labour is included was 0.79, 0.51 and 0.42 for strata 1, 2 and
      3, respectively. When family labour is not included, the PCR was 0.07, 0.25 and
      0.26. Net profit per litre of milk including family labour was US$0.03 l(-1) for
      Stratum 1, US$0.09 for Stratum 2 and US$0.12 l(-1) for Stratum 3; but increased
      to $0.12, 0.14 and 0.15, respectively, when the economic cost of family labour is
      not included. It is concluded that family labour is a crucial factor in the
      profitability and competitiveness of small-scale dairy production. 

PMID- 24097247
TI  - Lumpy skin disease of cattle: an emerging problem in the Sultanate of Oman.
AB  - Lumpy skin disease (LSD) is a highly infectious disease of cattle caused by a
      virus belonging to the Capripoxvirus genus of the family Poxviridae. The purpose
      of this study is to place on record the first confirmation of LSD in the
      Sultanate. The disease was diagnosed and confirmed using polymerase chain
      reaction, histopathology, transmission electron microscopy and serum
      neutralization testing. The epizootic occurred in 2009 involving a large number
      of animals and covering a wide area including Nezwa, Alqabel, Sohar, Saham and
      Burimi. Morbidity and mortality rates of 29.7 and 26.3 %, and 13.6 and 15.4 %
      were observed at Nezwa and Sohar, respectively. The clinical signs were much more
      severe in Holstein-Friesian cattle compared to indigenous breeds and were
      characterized by multiple skin nodules covering the neck, back, perineum, tail,
      limbs and genital organs. Affected animals also exhibited lameness, emaciation
      and cessation of milk production. Oedema of limbs and brisket, and superficial
      lymph node enlargement were highly prominent. It is not known from where the
      virus originated, or how it spread to the Sultanate. The disease has become
      endemic in the country and is liable to extend to other Gulf Cooperation Council
      Countries and cause a pandemic. It is of major concern to the Omani dairy
      industry. Due to the widespread presence of screw worm, serious economic losses
      can follow outbreaks. 

PMID- 24097249
TI  - Challenges in measuring antibiotic consumption.
AB  - The measurement of antibacterial consumption is important for tracking use over
      time, for assessing correlations between use and antibacterial resistance, and
      for serving as an outcome measure for antimicrobial stewardship programs.
      Accurate and consistent measures of use are important for meaningful inter- and
      intrainstitutional comparisons. The defined daily dose (DDD) and days of therapy
      methods are commonly used measures in the adult population; however, there is no
      one ideal measure of consumption that covers the breadth and depth of
      antibacterial prescribing. The use of the DDD and the prescribed daily dose
      methods, with further stratification of use by weight and age groups, aids in the
      evaluation of antimicrobial use in pediatric patients. Increasing availability of
      computerized pharmacy data should enhance the collection and analysis of data
      from hospitals. 

PMID- 24097250
TI  - On the Markovian approach for modeling the dynamics of nosocomial infections.
AB  - We analyze the dynamics of nosocomial infections in intensive care units (ICUs)
      by using a Markov chain model. Since population size in the ICU is small, in
      contrast to previous studies, we concentrate on the analytical solution rather
      than using simulation. We investigate how changes in the system parameters affect
      to some important behavioral indicators of the spread of the pathogen. We also
      present an exact measure of the number of secondary cases of infection produced
      by one colonized patient. 

PMID- 24097248
TI  - Association of serum carotenoid levels with urinary albumin excretion in a
      general Japanese population: the Yakumo study.
AB  - BACKGROUND: Albuminuria is a risk factor for not only nephropathy progression but
      also cardiovascular disease. Oxidative stress may have a role in the positive
      association between albuminuria and cardiovascular disease. METHODS: This cross
      sectional study investigated the associations of serum levels of carotenoids,
      which are dietary antioxidants, with albuminuria among 501 Japanese adults (198
      men, mean age +/- SD: 66.4 +/- 10.0 years; 303 women, mean age +/- SD: 65.4 +/-
      9.8 years) who attended a health examination. Serum levels of carotenoids were
      determined by high-performance liquid chromatography. Logistic regression
      analysis was used to estimate odds ratios (ORs) with 95% CIs for albuminuria
      after adjustment for age, body mass index, smoking habits, drinking habits,
      hypertension, diabetes mellitus, and dyslipidemia. RESULTS: Prevalence of
      albuminuria was 15.4% among men and 18.1% among women. Among women with
      albuminuria, geometric mean serum levels of canthaxanthin, lycopene, beta
      carotene, total carotenes, and provitamin A were significantly lower than those
      of normoalbuminuric women. Adjusted ORs for albuminuria among women in the
      highest tertiles of serum beta-carotene (OR, 0.45; 95% CI, 0.20-0.98) and
      provitamin A (OR, 0.45; 95% CI, 0.20-0.97) were significantly lower as compared
      with those for women in the lowest tertile. There were no associations between
      serum carotenoids and albuminuria in men. CONCLUSIONS: An increased level of
      serum provitamin A, especially serum beta-carotene, was independently associated
      with lower risk of albuminuria among Japanese women.

PMID- 24097251
TI  - Author of race discrimination report claims he was pressured to modify covering
      letter.

PMID- 24097252
TI  - High Court quashes tribunal's judgment on police doctor.

PMID- 24097253
TI  - Hunt wants to be "most pro-GP health secretary in a generation".

PMID- 24097254
TI  - Role of preferential weak hybridization between the surface-state of a metal and
      the oxygen atom in the chemical adsorption mechanism.
AB  - We report on the chemical adsorption mechanism of atomic oxygen on the Pt(111)
      surface using angle-resolved-photoemission spectroscopy (ARPES) and density
      functional calculations. The detailed band structure of Pt(111) from ARPES
      reveals that most of the bands near the Fermi level are surface-states. By
      comparing band maps of Pt and O/Pt, we identify that dxz (dyz) and dz(2) orbitals
      are strongly correlated in the surface-states around the symmetry point M and K,
      respectively. Additionally, we demonstrate that the s- or p-orbital of oxygen
      atoms hybridizes preferentially with the dxz (dyz) orbital near the M symmetry
      point. This weak hybridization occurs with minimal charge transfer. 

PMID- 24097256
TI  - Topical negative pressure to treat surgical site infections, with a focus on post
      sternotomy infections: a systematic review and meta-analysis.
AB  - PURPOSE: Topical negative pressure (TNP) has become a common treatment of
      infected wounds. A systematic review and meta-analysis was performed to
      investigate TNP efficacy compared to conventional therapy in the treatment of
      deep surgical site infections (SSIs), particularly post-sternotomy infections.
      METHODS: MEDLINE, EMBASE, and Cochrane Central Register of Controlled Trials were
      searched for randomized clinical trials (RCTs) and observational studies
      comparing TNP to conventional treatment in deep SSIs published up to February
      2012. Study quality was evaluated through the GRADE system and bias risk through
      the Newcastle-Ottawa scale (NOS). Primary outcome was infection cure/wound
      resolution rate. Secondary outcomes were adverse events, length of stay,
      mortality, and costs. The results are presented with 95 % confidence intervals
      (95 % CIs) and report estimates as odds ratios (ORs). Heterogeneity was
      determined through the I (2) test, with >50 % being considered significant.
      RESULTS: Among 83 studies retrieved, 12 cohort studies including 873 patients
      were considered. All the studies were of low quality, 11/12 had a medium risk of
      bias, and none were RCTs. Wound resolution was obtained more frequently in TNP
      treated patients as compared with continuous and closed drainage (OR 6.45, 95 %
      CI 3.46-12.00). TNP use was associated with significant reduction of length of
      stay compared with standard of care (mean difference: 8.21, 95 % CI -12.19, 
      4.23). High heterogeneity was detected between studies, explained by the TNP
      comparator type. CONCLUSIONS: The systematic review and meta-analysis suggest
      that TNP might be more effective than standard therapy in the cure of deep SSIs.
      However, multicenter RCTs are needed to confirm the potential value of this
      treatment.

PMID- 24097258
TI  - Anisotropic magnetic properties and crystal electric field studies on CePd2Ge2
      single crystal.
AB  - The anisotropic magnetic properties of the antiferromagnetic compound CePd2Ge2,
      crystallizing in the tetragonal crystal structure have been investigated in
      detail on a single crystal grown by the Czochralski method. From the electrical
      transport, magnetization and heat capacity data, the Neel temperature is
      confirmed to be 5.1 K. Anisotropic behaviour of the magnetization and resistivity
      is observed along the two principal crystallographic directions-namely, [100] and
      [001]. The isothermal magnetization measured in the magnetically ordered state at
      2 K exhibits a spin reorientation at 13.5 T for the field applied along the [100]
      direction, whereas the magnetization is linear along the [001] direction
      attaining a value of 0.94 MU(B)/Ce at 14 T. The reduced value of the
      magnetization is attributed to the crystalline electric field (CEF) effects. A
      sharp jump in the specific heat at the magnetic ordering temperature is observed.
      After subtracting the phononic contribution, the jump in the heat capacity
      amounts to 12.5 J K(-1)mol(-1) which is the expected value for a spin 1/2 system.
      From the CEF analysis of the magnetization data the excited crystal field split
      energy levels were estimated to be at 120 K and 230 K respectively, which
      quantitatively explains the observed Schottky anomaly in the heat capacity. A
      magnetic phase diagram has been constructed based on the field dependence of
      magnetic susceptibility and the heat capacity data.

PMID- 24097257
TI  - Archaeal ubiquitin-like SAMP3 is isopeptide-linked to proteins via a UbaA
      dependent mechanism.
AB  - SAMP1 and SAMP2 are ubiquitin-like proteins that function as protein modifiers
      and are required for the production of sulfur-containing biomolecules in the
      archaeon Haloferax volcanii. Here we report a novel small archaeal modifier
      protein (named SAMP3) with a beta-grasp fold and C-terminal diglycine motif
      characteristic of ubiquitin that is functional in protein conjugation in Hfx.
      volcanii. SAMP3 conjugates were dependent on the ubiquitin-activating E1 enzyme
      homolog of archaea (UbaA) for synthesis and were cleaved by the JAMM/MPN+ domain
      metalloprotease HvJAMM1. Twenty-three proteins (28 lysine residues) were found to
      be isopeptide-linked to the C-terminal carboxylate of SAMP3, and 331 proteins
      were reproducibly found associated with SAMP3 in a UbaA-dependent manner based on
      tandem mass spectrometry (MS/MS) analysis. The molybdopterin (MPT) synthase large
      subunit homolog MoaE, found samp3ylated at conserved active site lysine residues
      in MS/MS analysis, was also shown to be covalently bound to SAMP3 by
      immunoprecipitation and tandem affinity purifications. HvJAMM1 was demonstrated
      to catalyze the cleavage of SAMP3 from MoaE, suggesting a mechanism of
      controlling MPT synthase activity. The levels of samp3ylated proteins and samp3
      transcripts were found to be increased by the addition of dimethyl sulfoxide to
      aerobically growing cells. Thus, we propose a model in which samp3ylation is
      covalent and reversible and controls the activity of enzymes such as MPT
      synthase. Sampylation of MPT synthase may govern the levels of molybdenum
      cofactor available and thus facilitate the scavenging of oxygen prior to the
      transition to respiration with molybdenum-cofactor-containing terminal reductases
      that use alternative electron acceptors such as dimethyl sulfoxide. Overall, our
      study of SAMP3 provides new insight into the diversity of functional ubiquitin
      like protein modifiers and the network of ubiquitin-like protein targets in
      Archaea. 

PMID- 24097259
TI  - Clinical and radiological presentation of spinal epidural haemangiomas: clinical
      series in a tertiary care centre during a 10-year period.
AB  - PURPOSE: Haemangiomas are very frequent benign spinal tumours. However, pure
      epidural location is extremely rare. At present, only 52 cases have been reported
      in the literature during the last 10 years. We proposed to analyse clinical and
      radiological features of this rare entity treated in a tertiary care centre over
      the last 10 years. METHODS: A study of a retrospective surgical series (2002
      2012) was conducted. The clinic's electronic database was searched for "spinal"
      and/or "vertebral haemangiomas", which were treated by surgery and/or
      vertebroplasty. Clinical, radiological and histopathological data were analysed.
      RESULTS: In total, the series comprised 30 spinal haemangiomas. There were 6
      epidural (20 %), 17 vertebral (57 %) and 7 intradural lesions (23 %). There were
      four men and two women, mean age 28.3 years, with epidural lesions. One patient
      presented with localised back pain only, two with radiculopathy and focal
      neurological deficit, two with radiculopathy only and one with isolated focal
      neurological deficit, respectively. The onset of symptoms was progressive in four
      cases over weeks to months and sudden in two cases. Preoperative MRI imaging
      revealed features of meningioma, neurinoma or metastasis. CONCLUSION: Epidural
      haemangiomas are extremely rare spinal lesions. They may mimic more common spinal
      tumours clinically and radiologically. The usual treatment is gross total
      resection confirming the diagnosis histologically.

PMID- 24097260
TI  - Factors associated with the development of self-harm amongst a socio-economically
      deprived cohort of adolescents in Santiago, Chile.
AB  - PURPOSE: Studies carried out in the West indicate that the incidence of self-harm
      (SH) is particularly high amongst adolescents, but few studies have investigated
      its incidence and aetiology in low-income countries. The purpose of this study
      was to investigate risk factors associated with new onset episodes of SH, amongst
      Chilean adolescents from low socio-economic backgrounds. METHODS: Prospective
      cohort study nested within a cluster randomised controlled trial. A 6-month
      follow-up for 2,042 adolescents, median age 14 years, from socio-economically
      deprived areas of Santiago, Chile. RESULTS: The lifetime prevalence of SH was
      23%. The incidence rate of SH at 6 months was 14% amongst those reporting no SH
      at baseline. In multivariable analyses, risk factors for incident SH include
      depressive symptoms, suicidal thoughts, poor problem-solving skills and cannabis
      misuse. CONCLUSIONS: The prevalence and incidence of SH in this socio
      economically deprived sample differed highly according to gender. Poor problem
      solving skills, suicidal thoughts, and cannabis misuse were associated with onset
      of SH.

PMID- 24097261
TI  - Current status of percutaneous vertebroplasty and percutaneous kyphoplasty--a
      review.
AB  - Percutaneous vertebroplasty (PV) and kyphoplasty (PK) are the 2vertebral
      augmentation procedures that have emerged as minimally invasive surgical options
      to treat painful vertebral compression fractures (VCF) during the last 2 decades.
      VCF may either be osteoporotic or tumor-associated. Two hundred million women are
      affected by osteoporosis globally. Vertebral fracture may result in acute pain
      around the fracture site, loss of vertebral height due to vertebral collapse,
      spinal instability, and kyphotic deformity. The main goal of the PV and PK
      procedures is to give immediate pain relief to patients and restore the vertebral
      height lost due to fracture. In percutaneous vertebroplasty, bone cement is
      injected through a minimal incision into the fractured site. Kyphoplasty involves
      insertion of a balloon into the fractured site, followed by inflation-deflation
      to create a cavity into which the filler material is injected, and the balloon is
      taken out prior to cement injection. This literature review presents a
      qualitative overview on the current status of vertebral augmentation
      procedures,especially PV and PK, and compares the efficacy and safety of these 2
      procedures. The review consists of a brief history of the development of these 2
      techniques, a discussion on the current research on the bone cement, clinical
      outcome of the 2 procedures, and it also sheds light on ongoing and future
      research to maximize the efficacy and safety of vertebral augmentation
      procedures. 

PMID- 24097262
TI  - Identification and characterization of NF-Y transcription factor families in
      Canola (Brassica napus L.).
AB  - NF-Y (NUCLEAR FACTOR-Y), a heterotrimeric transcription factor, is composed of NF
      YA, NF-YB, and NF-YC proteins in yeast, animal, and plant systems. In plants,
      each of the NF-YA/B/C subunit forms a multi-member family. NF-Ys are key
      regulators with important roles in many physiological processes, such as drought
      tolerance, flowering time, and seed development. In this study, we identified,
      annotated, and further characterized 14 NF-YA, 14 NF-YB, and 5 NF-YC proteins in
      Brassica napus (canola). Phylogenetic analysis revealed that the NF-YA/B/C
      subunits were more closely clustered with the Arabidopsis thaliana (Arabidopsis)
      homologs than with rice OsHAP2/3/5 subunits. Analyses of the conserved domain
      indicated that the BnNF-YA/B/C subfamilies, respectively, shared the same
      conserved domains with those in other organisms, including Homo sapiens,
      Saccharomyces cerevisiae, Arabidopsis, and Oryza sativa (rice). An examination of
      exon/intron structures revealed that most gene structures of BnNF-Y were similar
      to their homologs in Arabidopsis, a model dicot plant, but different from those
      in the model monocot plant rice, suggesting that plant NF-Ys diverged before
      monocot and dicot plants differentiated. Spatial-tempo expression patterns, as
      determined by qRT-PCR, showed that most BnNF-Ys were widely expressed in
      different tissues throughout the canola life cycle and that several closely
      related BnNF-Y subunits had similar expression profiles. Based on these findings,
      we predict that BnNF-Y proteins have functions that are conserved in the
      homologous proteins in other plants. This study provides the first extensive
      evaluation of the BnNF-Y family, and provides a useful foundation for dissecting
      the functions of BnNF-Y. 

PMID- 24097263
TI  - Genome-wide study of NAGNAG alternative splicing in Arabidopsis.
AB  - NAGNAG alternative splicing is one type of alternative splicing in mammals and
      plants. There are two opposite arguments regarding the mechanism of this NAGNAG
      event, i.e. whether splice variation is controllable by the cell or is just
      biological noise. In this paper, we systematically investigated NAGNAG acceptors
      in Arabidopsis thaliana using both cDNA/EST and RNA-Seq data. We identified 9,473
      NAGNAG motifs, including 529 cDNA/EST-confirmed NAGNAG acceptors. A nomenclature
      tree for this type of alternative splicing was defined based on the cDNA/EST
      validation, location in the exon, sequence and expression level. Low expression
      of some NAGNAG motifs was observed in various tissues or pathogen-infected
      samples, indicating the existence of background splicing. Tissue-specific or
      treatment-specific differences in the dynamic profiles suggest that some NAGNAG
      acceptors are highly regulated. 

PMID- 24097264
TI  - Plastidic protein Cdf1 is essential in Arabidopsis embryogenesis.
AB  - Arabidopsis cell growth defect factor-1 (Cdf1 in yeast, At5g23040) was originally
      isolated as a cell growth suppressor of yeast from genetic screening. To
      investigate the in vivo role of Cdf1 in plants, a T-DNA insertion line was
      analyzed. A homozygous T-DNA insertion mutant (cdf1/cdf1) was embryo lethal and
      showed arrested embryogenesis at the globular stage. The Cdf1 protein, when fused
      with green fluorescent protein, was localized to the plastid in stomatal guard
      cells and mesophyll cells. A promoter-beta-glucuronidase assay found expression
      of Cdf1 in the early heart stage of embryogenesis, suggesting that Cdf1 was
      essential for Arabidopsis embryogenesis during the transition of the embryo from
      the globular to heart stage. 

PMID- 24097265
TI  - Summaries for patients. Screening for high blood pressure in children and
      adolescents: U.S. Preventive Services Task Force recommendation statement.

PMID- 24097266
TI  - Nonoccupational environmental exposure to manganese is linked to deficits in
      peripheral and central olfactory function.
AB  - Manganese is of growing concern as a toxic air pollutant. It is readily
      transported from the olfactory epithelium to the olfactory bulb, and unlike other
      metals, it is transported transynaptically to structures deep within the brain.
      However, little is known regarding the possible effect of nonoccupational
      exposure to manganese on olfactory function. Using the Sniffin' Sticks test
      battery, we compared the olfactory performance of subjects from a manganese
      mining district living <1 km from a manganese processing plant, with nonexposed
      subjects living 50 km from the closest source of exposure (N = 30/group). Groups
      were matched for age, sex, and schooling, and none had ever worked in mining
      related activities. Concentrations of manganese in hair were measured as a
      biomarker of exposure; exposed subjects had significantly higher concentrations
      than nonexposed subjects. They were also significantly outperformed by the
      nonexposed subjects on all olfactory measures (threshold, discrimination, and
      identification), indicating adverse effects of manganese exposure on a range of
      olfactory functions, including those involving higher order cognitive processes.
      This contrasts with previous findings showing adverse peripheral but not central
      effects on olfactory function of big city air pollution, which mostly consists of
      toxicants known to affect the olfactory epithelium but with lower transynaptic
      transport capacity compared with manganese. We conclude that nonoccupational
      exposure to airborne manganese is associated with decrements in both peripheral
      and central olfactory function. 

PMID- 24097267
TI  - Transposition of native chromatin for fast and sensitive epigenomic profiling of
      open chromatin, DNA-binding proteins and nucleosome position.
AB  - We describe an assay for transposase-accessible chromatin using sequencing (ATAC
      seq), based on direct in vitro transposition of sequencing adaptors into native
      chromatin, as a rapid and sensitive method for integrative epigenomic analysis.
      ATAC-seq captures open chromatin sites using a simple two-step protocol with 500
      50,000 cells and reveals the interplay between genomic locations of open
      chromatin, DNA-binding proteins, individual nucleosomes and chromatin compaction
      at nucleotide resolution. We discovered classes of DNA-binding factors that
      strictly avoided, could tolerate or tended to overlap with nucleosomes. Using
      ATAC-seq maps of human CD4(+) T cells from a proband obtained on consecutive
      days, we demonstrated the feasibility of analyzing an individual's epigenome on a
      timescale compatible with clinical decision-making. 

PMID- 24097268
TI  - Predicting functional gene interactions with the hierarchical interaction score.
AB  - Systems biology aims to unravel the vast network of functional interactions that
      govern biological systems. To date, the inference of gene interactions from large
      scale 'omics data is typically achieved using correlations. We present the
      hierarchical interaction score (HIS) and show that the HIS outperforms commonly
      used methods in the inference of functional interactions between genes measured
      in large-scale experiments, making it a valuable statistic for systems biology. 

PMID- 24097269
TI  - Image-based transcriptomics in thousands of single human cells at single-molecule
      resolution.
AB  - Fluorescence in situ hybridization (FISH) is widely used to obtain information
      about transcript copy number and subcellular localization in single cells.
      However, current approaches do not readily scale to the analysis of whole
      transcriptomes. Here we show that branched DNA technology combined with automated
      liquid handling, high-content imaging and quantitative image analysis allows
      highly reproducible quantification of transcript abundance in thousands of single
      cells at single-molecule resolution. In addition, it allows extraction of a
      multivariate feature set quantifying subcellular patterning and spatial
      properties of transcripts and their cell-to-cell variability. This has multiple
      implications for the functional interpretation of cell-to-cell variability in
      gene expression and enables the unbiased identification of functionally relevant
      in situ signatures of the transcriptome without the need for perturbations.
      Because this method can be incorporated in a wide variety of high-throughput
      image-based approaches, we expect it to be broadly applicable. 

PMID- 24097270
TI  - pLogo: a probabilistic approach to visualizing sequence motifs.
AB  - Methods for visualizing protein or nucleic acid motifs have traditionally relied
      upon residue frequencies to graphically scale character heights. We describe the
      pLogo, a motif visualization in which residue heights are scaled relative to
      their statistical significance. A pLogo generation tool is publicly available at
      http://plogo.uconn.edu/ and supports real-time conditional probability
      calculations and visualizations. 

PMID- 24097271
TI  - Instant super-resolution imaging in live cells and embryos via analog image
      processing.
AB  - Existing super-resolution fluorescence microscopes compromise acquisition speed
      to provide subdiffractive sample information. We report an analog implementation
      of structured illumination microscopy that enables three-dimensional (3D) super
      resolution imaging with a lateral resolution of 145 nm and an axial resolution of
      350 nm at acquisition speeds up to 100 Hz. By using optical instead of digital
      image-processing operations, we removed the need to capture, store and combine
      multiple camera exposures, increasing data acquisition rates 10- to 100-fold over
      other super-resolution microscopes and acquiring and displaying super-resolution
      images in real time. Low excitation intensities allow imaging over hundreds of 2D
      sections, and combined physical and computational sectioning allow similar depth
      penetration to spinning-disk confocal microscopy. We demonstrate the capability
      of our system by imaging fine, rapidly moving structures including motor-driven
      organelles in human lung fibroblasts and the cytoskeleton of flowing blood cells
      within developing zebrafish embryos. 

PMID- 24097272
TI  - VEGFA rSNPs, transcriptional factor binding sites and human disease.
AB  - Three regulatory SNPs (rSNPs) in the promoter region of the vascular endothelial
      growth factor-A (VEGFA) gene have been significantly associated with several
      human diseases or conditions. The rSNP alleles alter the DNA landscape for
      potential transcriptional factors to attach, resulting in changes in
      transcriptional factor binding sites (TFBS). These TFBS changes are examined with
      respect to the human diseases which have been found to be significantly
      associated with the rSNPs. 

PMID- 24097273
TI  - Effects of initial combined tamsulosin and solifenacin therapy for overactive
      bladder and bladder outlet obstruction secondary to benign prostatic hyperplasia:
      a prospective, randomized, multicenter study.
AB  - PURPOSE: The purpose of the study is to evaluate the clinical efficacy of initial
      combined therapy of an alpha-blocker and anticholinergic agent compared with the
      alpha-blocker alone in patients with benign prostatic hyperplasia (BPH) with
      overactive bladder (OAB). METHODS: Hundred and fifty-six BPH patients with
      International Prostate Symptom Score (IPSS) of over 14 (voiding sub-score >= 8
      and storage sub-score >= 6) were prospectively included in Korea. Group 1 (n =
      69) was the patients who were treated with Tamsulosin 0.2 mg daily alone for 4
      weeks and after 8 weeks they were treated with tamsulosin 0.2 mg and solifenacin
      5.0 mg daily combination. Group 2 (n = 70) was the patients who were treated
      initially with tamsulosin 0.2 mg and solifenacin 5.0 mg combination for 12 weeks.
      Detailed questionnaires were used to assess treatment satisfaction at 4th week
      and at 12th week of treatment in 2 groups. RESULTS: Baseline characteristics were
      not different between the 2 groups. In the 4th week, there was no difference
      between the 2 groups with regard to IPSS total score and voiding symptom score,
      although the IPSS storage symptom score was significantly lower in the Group 2 [
      2.0 (0.2) ?23.8 vs. -3.0 (0.2) ?35.7] (P < 0.001). In the 12th week, there was
      improvement in storage indices such as IPSS storage symptom score, OABSS, and
      urgency symptoms compared with baseline in each group (P < 0.001). No statistical
      differences in storage indices observed between the two groups at 12 week.
      CONCLUSIONS: Earlier treatment with alpha-blocker and anticholinergic agent
      helped to improve storage symptoms and quality-of-life scores earlier for
      patients with lower urinary tract symptoms related to BPH and OAB symptoms.

PMID- 24097274
TI  - Causes of death in peritoneal dialysis patients with different kidney diseases
      and comorbidities: a retrospective clinical analysis in a Chinese center.
AB  - OBJECTIVES: The objective of the study is to identify and compare the different
      causes of death among peritoneal dialysis (PD) patients varying in baseline
      characteristics, including gender, age, primary diseases, and comorbidities and
      to assess risk factors for first-year death. METHODS: The clinical data of 179 PD
      patients who were regularly followed up in our hospital and died between January
      2006 and February 2011 were retrospectively reviewed. RESULTS: Median age at PD
      catheter implantation was 73 years. The most common primary diseases leading to
      ESRD were diabetic nephropathy (DN; 26.3 %), chronic glomerulonephritis (CGN;
      24.6 %), and hypertensive nephropathy (HN; 21.8 %). The main causes of death in
      the DN and CGN groups were infections (42.6 %) and cardiocerebrovascular
      accidents (34.1 %), respectively. Patients with systemic vasculitis (SV) had the
      highest mortality rate from infection (71.4 %). Cox regression model showed that,
      compared with patients with CGN, those who had primary disease of DN, renal
      amyloidosis, multiple myeloma, or vasculitis were at higher risk of first-year
      death. Cerebrovascular disease, chronic heart failure, and/or lower serum albumin
      at baseline were also risk factors for first-year death. CONCLUSIONS: The main
      causes of death in PD patients with DN and CGN were infections and
      cardiocerebrovascular accidents, respectively. Risk factors for first-year death
      included the primary diseases, cerebrovascular diseases, chronic heart failure,
      and lower serum albumin at baseline.

PMID- 24097275
TI  - Comparison of erythropoietin and sildenafil protective role against
      ischemia/reperfusion injury of the testis in adult rats.
AB  - PURPOSE: Tissue damage in testicular torsion/detorsion is caused not only by the
      ischemia, but also by the ischemia/reperfusion injury after detorsion.
      Erythropoietin and sildenafil are considered to protect against
      ischemia/reperfusion injury. Here, we studied and compared their actions in
      testicular torsion/detorsion in adult rats. METHODS: Twenty-two adult male Wistar
      Albino rats were divided into four groups. Rats in group A (n = 5) were sham
      operated. Rats in group B (n = 5), group C (n = 6) and group D (n = 6) underwent
      torsion of the right testis and detorsion after 90 min. No pharmaceutical
      intervention was performed in group B. Erythropoietin (1,000 IU/kg) and
      sildenafil (0.7 mg/kg) were injected intraperitoneally in groups C and D,
      respectively, after 60 min of torsion. All animals were killed 24 h after
      detorsion, and their right testis was extracted, placed into 10 % formalin
      solution and sent for histopathological examination. The histological changes in
      the testes were scored according to the four-point grading system proposed by
      Cosentino et al. RESULTS: All rats in group A had normal testicular architecture
      (grade 1). The untreated group B had a mean grade of 3.81 (range 3.65-4). The
      treated groups C (mean grade 3.24; range 3.05-3.45) and D (2.69, range 2.4-2.9)
      presented statistically significant better results (lower grades) compared with
      the untreated group B. Group D had significantly better results (lower grades)
      than group C. CONCLUSIONS: The intraperitoneal injection of erythropoietin and
      sildenafil protects against ischemia/reperfusion injury after testicular torsion
      and detorsion. Sildenafil may have a stronger action than erythropoietin at the
      doses used in this study.

PMID- 24097276
TI  - Bioengineered kidneys: new sights on a distant horizon.
AB  - The need for renal replacement therapy is currently rising at an annually
      increasing rate. Current treatment options for patients with end-stage kidney
      disease include dialysis or organ transplantation. Yet, even though transplant
      survival has increased due to refined immunosuppressive therapy, morbidity
      remains high because of organ shortage. Here we discuss a recent publication that
      describes the transplantation of a bioengineered biocompatible kidney from a
      decellularized organ scaffold, thus possibly providing a solution to both
      transplant organ shortage and morbidity associated with long-term
      immunosuppression. 

PMID- 24097277
TI  - The efficacy and safety of simultaneous transurethral GreenLight photoselective
      vaporization of bladder tumor and prostate in patients with bladder tumor and
      lower urinary tract symptoms.
AB  - PURPOSE: We compared the safety and efficacy of simultaneous transurethral
      GreenLight photoselective vaporization of bladder tumor and prostate (PVBT/PVP)
      in patients with bladder tumor and bladder outlet obstruction caused by benign
      prostate hyperplasia (BPH). METHODS: Sixty-two patients with bladder tumor were
      enrolled in our prospective and randomized trial. A total of 37 men underwent
      simultaneous transurethral PVBT/PVP, and 25 patients underwent PVBT alone. The
      clinicopathological parameters and the recurrence of bladder tumor on the bladder
      neck/prostatic fossa were evaluated in all patients. RESULTS: Clinicopathological
      parameters of both groups were similar. The rates of recurrence, progression and
      tumor recurrence of bladder neck/prostatic fossa were 16.0, 4.0 and 4.0 % in the
      simultaneous resection group, and 18.9, 5.4 and 8.1 % in the group PVBT,
      respectively. No statistically significant differences were found between the two
      groups (P > 0.05). CONCLUSIONS: Simultaneous PVBT/PVP may help decrease the
      overall recurrence rate and tumor recurrence in bladder neck/prostatic fossa.
      PVBT/PVP can be performed effectively and safely in patients with bladder tumor
      and BPH.

PMID- 24097278
TI  - Pediatric metanephric adenoma: case report and review of the literature.
AB  - Metanephric adenomas are rare benign renal neoplasms, uncommonly seen in the
      pediatric population. They are typically detected incidentally on imaging studies
      performed for unrelated clinical presentations. Preoperatively, the imaging
      appearance of this tumor overlaps with the appearance of more common and more
      aggressive renal neoplasms such as Wilms' tumor or renal cell carcinoma. We
      present a case of a pathologically proven metanephric adenoma, monitored
      preoperatively for approximately 5 years, prior to definitive nephrectomy. As the
      majority of solid renal masses are resected soon after they are detected, to the
      best of our knowledge, this case is the first to demonstrate the natural in vivo
      progression of a pathologically proven metanephric adenoma.

PMID- 24097279
TI  - A systematic theoretical study of the electronic structures of porphyrin dimers:
      DFT and TD-DFT calculations on diporphyrins linked by ethane, ethene, ethyne,
      imine, and azo bridges.
AB  - Theoretical calculations of the geometries, electronic structures and electronic
      absorption spectra of a series of covalently-linked porphyrin dimers are
      reported. The diporphyrins comprise 5,10,15-triphenylporphyrinatozinc(II)
      (ZnTriPP) units linked through the meso carbons by two-atom bridges, namely 1,2
      ethanediyl (1), trans-1,2-ethenediyl (2), ethynediyl (3), 1,2-iminomethenediyl
      (4), and transdiazenediyl (5). The structures were optimised in toluene solvent
      by Density Functional Theory (DFT), using the integral equation formalism variant
      of the polarizable continuum model. The calculations were performed using the
      B3LYP functional and the 6-31G(d,p) basis set. The complete molecules were
      modelled, with no substitution of smaller groups on the periphery. In parallel,
      the compounds 2-5 were prepared by known or novel synthetic routes, to enable
      comparisons of experimental electronic absorption spectra with those calculated
      using time dependent-DFT at the same level of theory. As the ethane dimer 1 is
      not yet synthetically accessible, the model monomer meso-2-phenylethylZnTriPP was
      used for comparisons with the theoretical predictions. The results form a self
      consistent set, enabling for the first time legitimate comparisons of the
      electronic structures of the series, especially regarding the degree to which the
      porphyrin p-systems interact by conjugation across the bridges. The theoretical
      calculations of the electronic transitions match the observed spectra in toluene
      to a remarkable degree, especially with respect to the peak maximum of the Q
      band, which represents to a large degree the energy of the HOMO-LUMO transition.
      The imine 4 is intrinsically polar due to the asymmetric bridge, and the HOMO is
      located almost exclusively on the ZnTriPP unit attached to the nitrogen of the
      imine, and the LUMO on the C-attached ring. Thus the Q-band transition is mapped
      as a comprehensive charge-transfer from the former ring to the latter. This may
      have consequences for the non-linear optical properties of the system. The
      azoporphyrin 5 exhibits the largest splittings between the interacting MOs via
      the conjugated bridge, vindicating a prediction by Anderson and co-workers in
      2002, and confirmed experimentally by our synthesis of 5. The collected results
      also indicate that this level of theory is more thanadequate as a model with
      which to handle these large delocalised molecules.

PMID- 24097280
TI  - Task-related training combined with transcutaneous electrical nerve stimulation
      promotes upper limb functions in patients with chronic stroke.
AB  - Severe upper limb paresis is a major contributor to disability after stroke. This
      study investigated the efficacy of task-related training (TRT) with
      transcutaneous electrical nerve stimulation (TENS) on recovery of upper limb
      motor function in chronic-stroke survivors. Thirty patients with chronic stroke
      were randomly allocated two groups: the TRT+TENS group (n = 15) and the
      TRT+placebo (TRT+PLBO) group (n = 15). Patients in the TRT+TENS group received
      TENS stimulation (two to three times the sensory threshold), while subjects in
      the TRT+PLBO group received TENS without real electrical stimulation. TENS was
      applied to muscle belly of triceps and wrist extensors, while placebo (PLBO)
      stimulation was administrated without real electrical stimulation. Both
      interventions were given for 30 minutes per day, 5 days per week, for a period of
      4 weeks. The primary outcomes were assessed with Fugl-Meyer assessment scores
      (FMA), Manual function test (MFT), Box and block test (BBT), and Modified
      Ashworth scale (MAS), each of which was performed one day before and one day
      after intervention. Both groups showed significant improvements in FMA, MFT, and
      BBT after intervention. When compared with the TRT+PLBO group, the TRT+TENS group
      showed significantly greater improvements in FMA (p = 0.034), MFT (p = 0.037),
      and BBT (p = 0.042). In MAS score, significant improvement was observed only in
      the TRT+TENS group (p = 0.011). Our findings indicate that TRT with TENS can
      reduce motor impairment and improve motor activity in stroke survivors with
      chronic upper limb paresis, highlighting the benefits of somatosensory
      stimulation from TENS. 

PMID- 24097281
TI  - Development of a tightly regulated and highly responsive copper-inducible gene
      expression system and its application to control of flowering time.
AB  - KEY MESSAGE: A newly developed copper-inducible gene expression system overcame
      the mixed results reported earlier, worked well both in cultured cells and a
      whole plant, and enabled to control flowering timing. Copper is one of the
      essential microelements and is readily taken up by plants. However, to date, it
      has rarely been used to control the expression of genes of interest, probably due
      to the inefficiency of the gene expression systems. In this study, we
      successfully developed a copper-inducible gene expression system that is based on
      the regulation of the yeast metallothionein gene. This system can be applied in
      the field and regulated at approximately one-hundredth of the rate used for
      registered copper-based fungicides. In the presence of copper, a translational
      fusion of the ACE1 transcription factor with the VP16 activation domain (VP16AD)
      of herpes simplex virus strongly activated transcription of the GFP gene in
      transgenic Arabidopsis. Interestingly, insertion of the To71 sequence, a 5'
      untranslated region of the 130k/180k gene of tomato mosaic virus, upstream of the
      GFP gene reduced the basal expression of GFP in the absence of copper to almost
      negligible levels, even in soil-grown plants that were supplemented with ordinary
      liquid nutrients. Exposure of plants to 100 MUM copper resulted in an over 1,000
      fold induction ratio at the transcriptional level of GFP. This induction was
      copper-specific and dose-dependent with rapid and reversible responses. Using
      this expression system, we also succeeded in regulating floral transition by
      copper treatment. These results indicate that our newly developed copper
      inducible system can accelerate gene functional analysis in model plants and can
      be used to generate novel agronomic traits in crop species.

PMID- 24097282
TI  - Hormonal treatment in recurrent and metastatic gynaecological cancers: a review
      of the current literature.
AB  - For many years hormonal treatment has played a role in the treatment of a
      selected group of patients with a variety of recurrent or metastatic
      gynaecological cancers, including ovarian and endometrial carcinomas, endometrial
      stromal sarcomas and granulosa cell tumours. Hormonal agents that are typically
      used include luteinizing-hormone-releasing hormone analogues, progestogens,
      selective oestrogen-receptor-modulating drugs such as tamoxifen, and more
      recently aromatase inhibitors. The rates of response to these drugs differ
      considerably depending on the tumour type, disease grade and stage as well as the
      type of drug used. Patients with granulosa cell tumours and endometrial stromal
      sarcomas have the highest response rates; owing to the rarity of these tumour
      types, the documented response rates are based on case reports and small series.
      Response rates in patients with recurrent and metastatic endometrial and ovarian
      carcinoma have been lower. It has been suggested that patients with well
      differentiated and hormone-receptor-positive carcinomas are more likely to
      benefit from hormonal treatment. However, the data to support this are limited,
      and at times conflicting, with very few prospective studies to date. This review
      updates the evidence for the use of hormonal treatment in patients with
      potentially hormone responsive recurrent and metastatic gynaecological cancers. 

PMID- 24097283
TI  - Electronic medical records and quality of cancer care.
AB  - The implementation of electronic medical records (EMR) systems was mandated by
      the U.S. federal government in large part due to research indicating that
      difficulty accessing clinical data was one of the most common causes of
      preventable deaths. Several assumptions were implicit in this mandate, including
      the assumption that the implementation of EMR would indeed improve clinicians'
      access to clinical data, that implementation of EMR would pose little to no risk
      to patients, and that the clinical benefit of improved access to clinical data
      would outweigh any risks that might arise. As detailed in this review, both
      formal research and extensive experiential observation have called all three
      assumptions into question. Specifically, as detailed below, there is clear
      evidence that EMR systems are associated with multiple specific risks to
      patients, whereas few, if any, scientifically rigorous outcomes-based studies
      have demonstrated that the potential benefits of EMR outweigh the known risks. In
      addition, there is currently little to no scientifically rigorous evidence that
      EMR systems constitute a cost-effective methodology for improving patient
      outcomes. 

PMID- 24097284
TI  - Organochlorine compound residues in muscle of wild boar (Sus scrofa L.) and red
      deer (Cervus elaphus L.): effects of age and sex.
AB  - Twenty-six organochlorine pesticides and 7 polychlorinated biphenyls were
      measured in muscle of wild boar and red deer from the Czech Republic. The
      concentration of DDT and its metabolites was higher (p < 0.01) in wild boar than
      in red deer, while PCBs and HCH were higher (p < 0.01) in red deer than in wild
      boar. The concentrations of DDT and its metabolites, hexachlorobenzene and
      hexachlorocyclohexane isomers were higher (p < 0.05) in juvenile wild boar than
      in adults. PCB 153 and p,p'-DDE were the most prominent pollutants in both red
      deer and wild boar. 

PMID- 24097285
TI  - Screening for primary hypertension in children and adolescents: U.S. Preventive
      Services Task Force recommendation statement.
AB  - DESCRIPTION: Update of the 2003 U.S. Preventive Services Task Force (USPSTF)
      recommendation on screening for high blood pressure in children and adolescents.
      METHODS: The USPSTF reviewed the evidence on screening and diagnostic accuracy of
      screening tests for blood pressure in children and adolescents, the effectiveness
      and harms of treatment of screen-detected primary childhood hypertension, and the
      association of hypertension with markers of cardiovascular disease in childhood
      and adulthood. POPULATION: This recommendation applies to children and
      adolescents who do not have symptoms of hypertension. RECOMMENDATION: The USPSTF
      concludes that the current evidence is insufficient to assess the balance of
      benefits and harms of screening for primary hypertension in asymptomatic children
      and adolescents to prevent subsequent cardiovascular disease in childhood or
      adulthood.

PMID- 24097286
TI  - Laser-controlled exciton Fano resonance in semiconductor superlattices.
AB  - Quantum control of excitonic Floquet states in semiconductor superlattices driven
      by an intense monochromatic laser is examined from a theoretical point of view.
      High-resolution optical absorption spectra, calculated using multichannel
      scattering theory with the R-matrix propagation method, clarified that the
      excitonic Fano resonance structure is induced by the laser field. Each of the
      physical quantities related to this resonance-such as the spectral intensity, an
      asymmetry parameter (q-parameter), a resonance width, and so on-shows a
      characteristic extremum as a function of laser strength (F(ac)) in the vicinity
      of a critical value of F(ac) where dynamic localization is realized. It has also
      been shown that this F(ac)-dependence is caused by an ac-Zener coupling between
      two photon sidebands. Further, we have shown that these quantities are also
      controlled by changing the laser frequency (omega), as well as F(ac), and the
      underlying physics is explained on the basis of anticrossing behavior of the two
      photon sidebands.

PMID- 24097287
TI  - Evaluating patient acceptability of a culturally focused psychiatric consultation
      intervention for Latino Americans with depression.
AB  - Significant disparities exist in both access to and quality of mental health care
      for Latino Americans with depression compared to Caucasians, resulting in a
      greater burden of disability in this underserved population. Our aim is to
      evaluate participant acceptability of a Culturally Focused Psychiatric (CFP)
      consultation program for depressed Latino Americans. Latino American adult
      primary care patients endorsing depressive symptoms on a screening questionnaire
      were targeted in their primary care clinic. The intervention addressed
      participants' depressive symptoms using culturally adapted clinical assessments
      and toolkits. Acceptability was evaluated using a treatment satisfaction scale
      and in-depth semi-structured interviews. Overall, 85% of participants responded
      positively to all questions of the satisfaction scale. In in-depth interviews,
      the vast majority of participants reported the program met expectations, all
      stated providers were culturally sensitive, and most stated recommendations were
      culturally sensitive. The CFP program was found to be acceptable to a group of
      depressed Latino American primary care patients. Further research is needed to
      evaluate if the CFP intervention can improve depressive symptoms and outcomes.

PMID- 24097288
TI  - Low-dose aspirin vs low-dose aspirin plus low-intensity warfarin in
      thromboprophylaxis: a prospective, multicentre, randomized, open, controlled
      trial in patients positive for antiphospholipid antibodies (ALIWAPAS).
AB  - OBJECTIVES: The objectives of this study are to examine the efficacy and safety
      of low-dose aspirin (LDA) vs LDA plus low-intensity warfarin (LDA + W) in the
      primary thrombosis prevention of aPL-positive patients with SLE and/or obstetric
      morbidity and the role of clinical and serological markers in the development of
      thrombosis. METHODS: In this 5-year prospective, randomized, open, controlled
      trial, 166 patients with aPL were randomly assigned using a minimization protocol
      to receive treatment with LDA (n = 82) or LDA + W [international normalized ratio
      (INR) = 1.5] (n = 84). Sixty-six patients who declined randomization were
      followed up in an observational arm. Clinical and laboratory characteristics and
      medication side effects were recorded. RESULTS: There were no differences in the
      number of thromboses between patients treated with LDA (4/82) or LDA + W (4/84)
      [hazard ratio (HR) 1.07, 95% CI 0.27, 4.3]. The incidence of thrombosis in the
      randomized patients was 8/166 (1.8 events/100 person-years) (HR 1.07, 95% CI
      0.27, 4.3) and in the observational arm was 7/66 (4.9 events/100 person-years)
      (HR 2.43, 95% CI 0.87, 6.79). Sixty-five of 66 patients included in the
      observational arm received LDA. None of the examined clinical or serological
      factors appeared to predict thrombosis. Medication side effects included mild
      gastrointestinal symptoms in the LDA group (n = 2) and bleeding in the LDA + W
      group (n = 11; 1 nasal and 10 menorrhagia). The risk difference for bleeding was
      13% (CI 6, 20). CONCLUSION: No differences in the number of thromboses were
      observed between patients treated with LDA vs those treated with LDA + W. More
      episodes of bleeding were detected in the LDA + W group. The LDA + W regime was
      significantly less safe and not as acceptable as LDA alone. TRIAL REGISTRATION:
      ISRCTN81818945; http://isrctn.org/.

PMID- 24097289
TI  - A cost-utility analysis of alternative drug regimens for newly diagnosed severe
      lupus nephritis patients in Thailand.
AB  - OBJECTIVE: The aim of this study was to assess the value of four drug regimens
      for newly diagnosed severe LN from a societal perspective. METHODS: A model-based
      cost-utility analysis was devised to measure lifetime costs and health outcomes.
      Current treatment options consisting of different combinations of i.v. CYC, AZA
      and MMF were compared with a baseline regimen of i.v. CYC in both the induction
      and maintenance phases. Resource use and costs were derived from medical records
      reviews and databases. Event rates were elicited from randomized controlled
      trials. Relative treatment effects were obtained from meta-analyses. Health
      utilities were obtained from a real cohort of patients to estimate the outcome of
      quality-adjusted life years. RESULTS: It was found that a treatment regimen that
      combined i.v. CYC in the induction phase with AZA in the maintenance phase was
      cost saving compared with the baseline regimen. Treatment with i.v. CYC in the
      induction phase and MMF in the maintenance phase and treatment with MMF in the
      induction phase and a reduced dose of the same in the maintenance phase turned
      out to be a negatively dominated regimen. CONCLUSION: In the Thai context, the
      combination of i.v. CYC for the induction phase followed by AZA for the
      maintenance phase should be considered as the first-line therapy for newly
      diagnosed severe LN, as it seems to be the most cost-saving regimen.

PMID- 24097290
TI  - Management of Takayasu arteritis: a systematic review.
AB  - Assessment of the pattern and extent of arterial involvement and measurement of
      current disease activity are essential for the management of Takayasu arteritis
      (TA). Since there is no completed, placebo-controlled, randomized clinical trial,
      the level of evidence for management of TA is low, generally reflecting the
      results of open studies, case series and expert opinion. The most commonly used
      agents include corticosteroids and conventional immunosuppressive agents such as
      MTX, AZA, MMF and LEF. In patients who remain resistant and/or intolerant to
      these agents, biologic drugs including TNF inhibitors, rituximab and tocilizumab
      seem to be promising. Antiplatelet treatment may also lower the frequency of
      ischaemic events in TA. In the presence of short-segment, critical arterial
      stenosis, balloon angioplasty or stent graft replacement may be useful. On the
      other hand, long-segment stenosis with extensive periarterial fibrosis or
      occlusion requires surgical bypass of the affected segment, which is clearly
      associated with superior results compared with endovascular intervention. As a
      general rule, both endovascular intervention and surgical procedures should be
      avoided during the active phase of the disease. Earlier diagnosis, better
      assessment of disease activity and future clinical trials will obviously improve
      the management of TA. 

PMID- 24097291
TI  - Upregulated expression of PERK in spinal ligament fibroblasts from the patients
      with ossification of the posterior longitudinal ligament.
AB  - PURPOSE: Molecular mechanism of ossification of the posterior longitudinal
      ligament (OPLL) remains unclear. This study was to investigate different
      expressions of PERK between the spinal ligament fibroblasts from OPLL patients
      and non-OPLL patients, and demonstrate knockdown of PERK protein expression by
      RNA interference inhibiting expression of osteocalcin (OCN), alkaline phosphatase
      (ALP), and type I collagen (COL I) in the cells from OPLL patients. METHODS:
      Spinal ligament cells were cultured using tissue fragment cell culture and
      identified by immunocytochemistry and immunofluorescence. The mRNA expression of
      osteoblast-specific genes of OCN, ALP and COL I was detected in the cells from
      OPLL and non-OPLL patients by semiquantitative reverse transcription-polymerase
      chain reaction. The protein expression of PERK was detected by Western blotting.
      And then, after 72 h, when RNA interference against PERK was performed on the
      cells from OPLL patients, expression of the osteoblast-specific genes was
      compared again between the transfection group and non-transfection group.
      RESULTS: Spinal ligament fibroblasts were observed 7-10 days after cell culture.
      Immunocytochemistry and immunofluorescence exhibited positive results of vimentin
      staining. The mRNA expressions of OCN, ALP and COL I and protein expression of
      PERK in the cells from OPLL patients were significantly greater than those from
      non-OPLL patients. In addition, knockdown of PERK protein expression inhibited
      the mRNA expressions of OCN, ALP and COL I remarkably in the transfection group
      compared with the non-transfection group, at 72 h after RNA interference
      targeting PERK was performed on the cells from OPLL patients. CONCLUSIONS: The
      cultured fibroblasts from OPLL patients exhibited osteogenic characteristics, and
      PERK-mediated ER stress might be involved in development of OPLL.

PMID- 24097292
TI  - Posture class prediction of pre-peak height velocity subjects according to gross
      body segment orientations using linear discriminant analysis.
AB  - BACKGROUND/PURPOSE: Measurement and classification of standing posture in the
      sagittal plane has important clinical implications for adolescent spinal
      disorders. Previous work using cluster analysis on three gross body segment
      orientation parameters (lower limbs, trunk, and entire body inclination) has
      identified three distinct postural groups of healthy subjects before pubertal
      peak growth: "neutral", "sway-back", and "leaning-forward". Although accurate
      postural subgrouping may be proposed to be crucial in understanding biomechanical
      challenges posed by usual standing, there is currently no objective method
      available for class assignment. Hence, this paper introduces a novel approach to
      subclassify new cases objectively according to their overall sagittal balance.
      METHODS: Postural data previously acquired from 1,196 pre-peak height velocity
      (pre-PHV) subjects were used in this study. To derive a classification rule for
      assigning a class label ("neutral", "sway-back", or "leaning-forward") to any new
      pre-PHV subjects, linear discriminant analysis was applied. Predictor variables
      were pelvic displacement, trunk lean and body lean angle. The performance of the
      newly developed classification algorithm was verified by adopting a cross
      validation procedure. RESULTS: The statistical model correctly classified over
      96.2% of original grouped subjects. In the cross-validation procedure used, over
      95.9% of subjects were correctly assigned. CONCLUSIONS: Based on three angular
      measures describing gross body segment orientation, our triage method is capable
      of reliably classifying pre-PHV subjects as either "neutral", "sway-back", or
      "leaning-forward". The discriminant prediction equations presented here enable a
      highly accurate posture class allocation of new cases with a prediction
      capability higher than 95.9%, thereby removing subjectivity from sagittal plane
      posture classification.

PMID- 24097293
TI  - Linear, non-linear optical susceptibilities and the hyperpolarizability of the
      mixed crystals Ag(0.5)Pb(1.75)Ge(S(1-x)Se(x))4: experiment and theory.
AB  - As the starting point for a comprehensive theoretical investigation of the linear
      and nonlinear optical susceptibilities, we have used our experimental
      crystallographic data for Ag0.5Pb1.75GeS3Se (Ag2Pb7Ge4S12Se4) reported. The
      experimental crystallographic positions were optimized by minimizing the forces
      acting on each atom to get meaningful theoretical predictions of the optical
      properties. The linear optical susceptibilities are calculated. We find that the
      optical band gap shows very good agreement with our measured gap. The second
      order nonlinear optical (NLO) susceptibilities dispersion namely the optical
      second harmonic generation (SHG) is calculated and compared with our experimental
      measurements. The microscopic first order hyperpolarizability, beta123, vector
      component along the principal dipole moment directions for the
      chi((2))(123)(omega) component was obtained theoretically and compared with our
      measured values at different temperatures. The dependence of the two-photon
      absorption (TPA) for the pump-probing at SHG of the microsecond CO2 laser was
      measured. In addition we explored the linear electro-optical effect in these
      crystals. This effect is described by the third rank polar tensors similarly to
      the SHG. However, for the Pockels effect besides the electronic contribution, the
      phonon subsystem also begins to play a principal role. As a consequence we study
      the dispersion of the linear electro-optical effects in the mentioned crystals.

PMID- 24097294
TI  - High-dose erythropoietin in acute ST-segment elevation myocardial infarction: a
      meta-analysis of randomized controlled trials.
AB  - OBJECTIVE: We sought to perform a meta-analysis to evaluate the potential
      influence of high-dose erythropoietin (EPO) on cardiac function parameters in
      patients with acute ST-segment elevation myocardial infarction (STEMI). METHODS
      AND RESULTS: By searching PubMed, EMBASE, and the Cochrane Library (up to
      December 2012), seven randomized controlled trials (RCTs) reporting cardiac
      functional parameters with a total of 1,250 acute STEMI patients were identified.
      When applied to patients with acute STEMI, high-dose EPO was relatively safe and
      no increase in all-caused death and severe adverse effects were indicated.
      Estimates were pooled from fixed or random effects models. Compared with
      controls, high-dose EPO resulted in a slight but significant improvement in left
      ventricular ejection fraction of 1.02 % [95 % confidence interval (CI) 0.17-1.88,
      P = 0.019, I (2) = 0 %] and an improvement in left ventricular end-systolic
      volume of -4.61 ml (95 % CI -7.64 to -1.58, P = 0.003, I (2) = 27.7 %).
      CONCLUSIONS: Available evidence suggested that high-dose EPO has limited cardio
      protective effects in patients with STEMI. However, considering the relatively
      short follow-up durations and small patient populations in the current RCTs, the
      effects of high-dose EPO on clinical outcomes in patients with STEMI need to be
      evaluated in larger prospective RCTs of longer duration.

PMID- 24097295
TI  - [Work environment measurements of nanoparticles in the nanoparticle-handling
      process using portable type particle sizer spectrometers].

PMID- 24097297
TI  - Mutation screen of the SIM1 gene in pediatric patients with early-onset obesity.
AB  - BACKGROUND: The transcription factor SIM1 (Single-minded 1) is involved in the
      control of food intake and in the pathogenesis of obesity. In mice, Sim1 is
      involved in the development of the paraventricular nucleus, and Sim1 deficiency
      leads to severe obesity and hyperphagia. In humans, chromosomal abnormalities in
      the SIM1 gene region have been reported in obese individuals. Furthermore, recent
      data also suggest that loss-of-function point mutations in SIM1 are responsible
      for SIM1 haplo-insufficiency that is involved in causing human obesity. In this
      study, we therefore wanted to expand the evidence regarding the involvement of
      SIM1 mutations in the pathogenesis of severe early-onset obesity. METHODS: We
      screened 561 severely overweight and obese children and adolescents and 453 lean
      adults for mutations in the coding region of the SIM1 gene. Mutation screening in
      all patients and lean individuals was performed by high-resolution melting curve
      analysis combined with direct sequencing. To evaluate the effect of the mutations
      on SIM1 transcriptional activity, luciferase reporter assays were performed.
      RESULTS: Mutation analysis identified four novel nonsynonymous coding variants in
      SIM1 in four unrelated obese individuals: p.L242V, p.T481K, p.A517V and p.D590E.
      Five synonymous variants, p.P57P, p.F93F, p.I183I, p.V208V and p.T653T, were also
      identified. Screening of the lean control population revealed the occurrence of
      four other rare SIM1 variants: p.G408R, p.R471P, p.S492P and p.S622F. For
      variants p.T481K and p.A517V, which were found in obese individuals, a decrease
      in SIM1 transcriptional activity was observed, whereas the transcriptional
      activity of all variants found in lean individuals resembled wild type.
      CONCLUSIONS: In this study, we have demonstrated the presence of rare SIM1
      variants in both an obese pediatric population and a population of lean adult
      controls. Further, we have shown that functional in vitro analysis of SIM1
      variants may help in distinguishing benign variants of no pathogenic significance
      from variants which contribute to the obesity phenotype.

PMID- 24097299
TI  - TRAIL negatively regulates VEGF-induced angiogenesis via caspase-8-mediated
      enzymatic and non-enzymatic functions.
AB  - Solid tumors supply oxygen and nutrients required for angiogenesis by producing
      vascular endothelial growth factor (VEGF). Thus, inhibitors of VEGF signaling
      abrogate tumor angiogenesis, resulting in the suppression of tumor growth and
      metastasis. We here investigated the effects of tumor necrosis factor-related
      apoptosis-inducing ligand (TRAIL) on VEGF-induced angiogenesis. TRAIL inhibited
      VEGF-induced in vitro angiogenesis of human umbilical vein endothelial cells
      (HUVECs) and in vivo neovascularization in chicken embryos and mice. TRAIL
      blocked VEGF-induced angiogenic signaling by inhibiting ERK, Src, FAK, paxillin,
      Akt, and eNOS. Further, TRAIL blocked intracellular Ca(2+) elevation and actin
      reorganization in HUVECs stimulated with VEGF, without inhibiting VEGF receptor-2
      tyrosine phosphorylation. TRAIL increased caspase-8 activity, without inducing
      caspase-9/-3 activation and apoptosis. Moreover, TRAIL resulted in cleavage of
      FAK into FAK-related non-kinase-like fragments in VEGF-stimulated HUVECs, which
      was blocked by a caspase-8 inhibitor and cellular caspase-8-like inhibitory
      protein. Biochemical and pharmacological inhibition of caspase-8 and FAK blocked
      the inhibitory effects of TRAIL on VEGF-stimulated anti-angiogenic signaling and
      events. In addition, caspase-8 knockdown also suppressed VEGF-mediated signaling
      and angiogenesis, suggesting that procaspase-8 plays a role of a non-apoptotic
      modulator in VEGF-induced angiogenic signaling. These results suggest that TRAIL
      inhibits VEGF-induced angiogenesis by increasing caspase-8 activity and
      subsequently decreasing non-apoptotic signaling functions of procaspase-8,
      without inducing caspase-3 activation and endothelial cell cytotoxicity. These
      data indicate that caspase-8 may be used as an anti-angiogenic drug for solid
      tumors resistant to TRAIL and anti-tumor drugs. 

PMID- 24097300
TI  - Tracheal extubation with a laryngeal mask airway and exchange catheter in a
      patient with a difficult airway.

PMID- 24097298
TI  - The association of birth order with later body mass index and blood pressure: a
      comparison between prospective cohort studies from the United Kingdom and Brazil.
AB  - BACKGROUND: Previous studies have found greater adiposity and cardiovascular risk
      in first born children. The causality of this association is not clear. Examining
      the association in diverse populations may lead to improved insight. METHODS: We
      examine the association between birth order and body mass index (BMI), systolic
      and diastolic blood pressure (SBP/DBP) in the 2004 Pelotas cohort from southern
      Brazil and the Avon Longitudinal Study of Parents and Children (ALSPAC) from
      Bristol, south-west England, restricting analysis to families with two children
      in order to remove confounding by family size. RESULTS: No consistent differences
      in BMI, SBP or DBP were observed comparing first and second born children. Within
      the Pelotas 2004 cohort, first born females were thinner, with lower SBP and DBP;
      for example, mean difference in SBP comparing first with second born was -0.979
      (95% confidence interval -2.901 to 0.943). In ALSPAC, first born females had
      higher BMI, SBP and DBP. In both cohorts, associations tended to be in the
      opposite direction in males, although no statistical evidence for gender
      interactions was found. CONCLUSIONS: The findings do not support an association
      between birth order and BMI or blood pressure. Differences to previous studies
      may be explained by differences in populations and/or confounding by family size
      in previous studies.

PMID- 24097301
TI  - New supraglottic airway with built-in pressure indicator decreases postoperative
      pharyngolaryngeal symptoms: a randomized controlled trial.
AB  - PURPOSE: Excessive supraglottic airway cuff pressure increases postoperative
      pharyngolaryngeal symptoms such as sore throat, dysphonia, and dysphagia. A new
      supraglottic airway, AES Ultra CPVTM (CPV), has a built-in intracuff pressure
      indicator. We hypothesized that using the CPV would reduce postoperative symptoms
      when compared with the LMA ClassicTM (LMA) without intracuff pressure guidance.
      METHODS: Ambulatory patients undergoing general anesthesia were randomized to
      either CPV or LMA. A size 3/4/5 was inserted according to manufacturer
      guidelines. Nitrous oxide was not used. In the LMA Group, the cuff was inflated
      according to manufacturer's guidelines. In the CPV Group, a CPV was inserted and
      the cuff inflated until the indicator was in the green zone (30-44 mmHg).
      Intracuff pressures were measured at five minutes and 20 min post-insertion in
      both groups. The primary outcome was the incidence of pharyngolaryngeal symptoms,
      defined as sore throat, dysphonia, and/or dysphagia at one, two, and/or 24 hr
      postoperatively. Continuous data were compared using Student's t test and
      categorical data were analyzed using Chi square analysis. RESULTS: The study
      included 170 patients, 85 per group. The mean (SD) intracuff pressure in the CPV
      group was significantly lower [44 (4) mmHg] than in the LMA Group [87 (37) mmHg];
      P < 0.001. The incidence of pharyngolaryngeal symptoms was significantly lower in
      the CPV Group than in the LMA Group (26% vs 49%; P = 0.002). The absolute risk
      reduction was 24%, and the number-needed-to-treat was 4.3. CONCLUSION: The
      incidence of postoperative pharyngolaryngeal symptoms in the CPV Group with a
      cuff pressure-guided strategy was significantly lower than in the LMA Group with
      standard practice. ( CLINICAL TRIAL REGISTRATION NUMBER: NCT01800344).

PMID- 24097302
TI  - 18F-FDG PET/CT for detection of malignant peripheral nerve sheath tumours in
      neurofibromatosis type 1: tumour-to-liver ratio is superior to an SUVmax cut-off.
AB  - OBJECTIVES: To evaluate the usefulness of normalising intra-tumour tracer
      accumulation on (18)F-fluorodeoxyglucose (FDG) positron emission
      tomography/computed tomography (PET/CT) to reference tissue uptake for
      characterisation of peripheral nerve sheath tumours (PNSTs) in neurofibromatosis
      type 1 (NF1) compared with the established maximum standardised uptake value
      (SUVmax) cut-off of >3.5. METHODS: Forty-nine patients underwent FDG PET/CT.
      Intra-tumour tracer uptake (SUVmax) was normalised to three different reference
      tissues (tumour-to-liver, tumour-to-muscle and tumour-to-fat ratios). Receiver
      operating characteristic (ROC) analyses were used out to assess the diagnostic
      performance. Histopathology and follow-up served as the reference standard.
      RESULTS: Intra-tumour tracer uptake correlated significantly with liver uptake
      (rs= 0.58, P = 0.016). On ROC analysis, the optimum threshold for tumour-to-liver
      ratio was >2.6 (AUC = 0.9735). Both the SUVmax cut-off value of >3.5 and a tumour
      to-liver ratio >2.6 provided a sensitivity of 100 %, but specificity was
      significantly higher for the latter (90.3% vs 79.8%; P = 0.013). CONCLUSIONS: In
      patients with NF1, quantitative (18)F-FDG PET imaging may identify malignant
      change in neurofibromas with high accuracy. Specificity could be significantly
      increased by using the tumour-to-liver ratio. The authors recommend further
      evaluation of a tumour-to-liver ratio cut-off value of >2.6 for diagnostic
      intervention planning. KEY POINTS: * (18)F-FDG PET/CT is used for detecting
      malignancy in PNSTs in NF1 patients * An SUV max cut-off value may give false
      positive results for benign plexiform neurofibromas * Specificity can be
      significantly increased using a tumour-to-liver ratio.

PMID- 24097303
TI  - 18F-FDG uptake in breast cancer correlates with immunohistochemically defined
      subtypes.
AB  - OBJECTIVES: To determine whether a correlation exists between maximum
      standardized uptake value (SUVmax) on (18)F-fluorodeoxyglucose positron emission
      tomography (FDG-PET) and the subtypes of breast cancer. METHODS: This
      retrospective study involved 548 patients (mean age 51.6 years, range 21-81
      years) with 552 index breast cancers (mean size 2.57 cm, range 1.0-14.5 cm). The
      correlation between (18)F-FDG uptake in PET/CT, expressed as SUVmax, and
      immunohistochemically defined subtypes (luminal A, luminal B, human epidermal
      growth factor receptor 2 (HER2) positive and triple negative) was analyzed.
      RESULTS: The mean SUVmax value of the 552 tumours was 6.07 +/- 4.63 (range 0.9
      32.8). The subtypes of the 552 tumours were 334 (60%) luminal A, 66 (12%) luminal
      B, 60 (11%) HER2 positive and 92 (17%) triple negative, for which the mean SUVmax
      values were 4.69 +/- 3.45, 6.51 +/- 4.18, 7.44 +/- 4.73 and 9.83 +/- 6.03,
      respectively. In a multivariate regression analysis, triple-negative and HER2
      positive tumours had 1.67-fold (P < 0.001) and 1.27-fold (P = 0.009) higher
      SUVmax values, respectively, than luminal A tumours after adjustment for invasive
      tumour size, lymph node involvement status and histologic grade. CONCLUSION: FDG
      uptake was independently associated with subtypes of invasive breast cancer.
      Triple-negative and HER2-positive breast cancers showed higher SUVmax values than
      luminal A tumours. KEY POINTS: * (18) F-FDG PET demonstrates increased tissue
      glucose metabolism, a hallmark of cancers. * Immunohistochemically defined
      subtypes appear significantly associated with FDG uptake (expressed as SUV max ).
      * Triple-negative tumours had 1.67-fold higher SUV max values than luminal A
      tumours. * HER2-positive tumours had 1.27-fold higher SUV max values than luminal
      A tumours.

PMID- 24097304
TI  - Prevention and treatment of bone changes associated with exposure to
      glucocorticoids.
AB  - Rheumatologic diseases are associated with a proinflammatory state, which is
      thought to lead to many of the bone changes seen in treatment-naive patients.
      However, glucocorticoids remain a common treatment option for rheumatologic
      diseases and are known to have a negative impact on bone through direct effects
      on bone cells and indirect effects on calcium absorption. Despite the anti
      inflammatory effect of glucocorticoids, fracture risk rises within the first 3
      months of treatment. As such, osteoporosis prevention and treatment needs to be
      considered in all patients started on chronic glucocorticoids (>=3 months of
      treatment). For very low risk patients, conservative management with non
      pharmacologic strategies may be appropriate. For the moderate to high fracture
      risk patients treated with glucocorticoids, pharmacologic treatment with 1 of the
      4 approved medications should be considered. The challenge of educating
      physicians and patients of the risks of glucocorticoid induced osteoporosis
      remain. 

PMID- 24097305
TI  - A 3-year survey quantifying the risk of dose escalation of benzodiazepines and
      congeners to identify risk factors to aid doctors to more rationale prescribing.
AB  - OBJECTIVES: This study investigated and quantified risk factors of dose
      escalation, as an indication of drug misuse and dependency of benzodiazepines and
      congeners, among presumably drug naive patients in the Norwegian drug
      prescription database, observed over 3 years. DESIGN: Observational study.
      SETTING: Prescription database study. PARTICIPANTS: We defined an excessive user
      as one redeeming more than two defined daily doses per day in 3 months. PRIMARY
      AND SECONDARY OUTCOME MEASURES: We examined the risk of excessive use over time
      and the effect of risk factors through multistate logistic regression and
      scenarios. RESULTS: Most of the 81 945 patients had zopiclone or zolpidem as the
      initial drug (63.8%), followed by diazepam (25.3%), oxazepam (6.1%),
      nitrazepam/flunitrazepam (2.9%), hydroxyzine/buspirone (1.6%) and alprazolam
      (0.3%). At any time 23% redeemed prescriptions, about 34% did not redeem any
      prescriptions beyond any 3-month period and 0.9% ended up as excessive users.
      Patients previously using drugs, such as opioids, antialcohol or smoke cessation
      treatment, had a higher risk to become excessive users compared to patients who
      had not. Patients whose first prescription was for oxazepam or
      nitrazepam/flunitrazepam had a higher risk of becoming an excessive user compared
      to those who started with diazepam. A specialist in general practice as the first
      time prescriber was associated with a lower risk compared to doctors without
      specialty. CONCLUSIONS: Most benzodiazepine use occurred according to guidelines.
      Still, some experienced dose escalation over time, and risk factors were previous
      use of other psychotropic drugs, long time use, choice of first-time drug and
      prescriber's specialty. This could incite doctors to have a cessation plan when
      issuing first-time prescriptions.

PMID- 24097306
TI  - Simulations of enhancer evolution provide mechanistic insights into gene
      regulation.
AB  - There is growing interest in models of regulatory sequence evolution. However,
      existing models specifically designed for regulatory sequences consider the
      independent evolution of individual transcription factor (TF)-binding sites,
      ignoring that the function and evolution of a binding site depends on its
      context, typically the cis-regulatory module (CRM) in which the site is located.
      Moreover, existing models do not account for the gene-specific roles of TF
      binding sites, primarily because their roles often are not well understood. We
      introduce two models of regulatory sequence evolution that address some of the
      shortcomings of existing models and implement simulation frameworks based on
      them. One model simulates the evolution of an individual binding site in the
      context of a CRM, while the other evolves an entire CRM. Both models use a state
      of-the art sequence-to-expression model to predict the effects of mutations on
      the regulatory output of the CRM and determine the strength of selection. We use
      the new framework to simulate the evolution of TF-binding sites in 37 well
      studied CRMs belonging to the anterior-posterior patterning system in Drosophila
      embryos. We show that these simulations provide accurate fits to evolutionary
      data from 12 Drosophila genomes, which includes statistics of binding site
      conservation on relatively short evolutionary scales and site loss across larger
      divergence times. The new framework allows us, for the first time, to test
      hypotheses regarding the underlying cis-regulatory code by directly comparing the
      evolutionary implications of the hypothesis with the observed evolutionary
      dynamics of binding sites. Using this capability, we find that explicitly
      modeling self-cooperative DNA binding by the TF Caudal (CAD) provides
      significantly better fits than an otherwise identical evolutionary simulation
      that lacks this mechanistic aspect. This hypothesis is further supported by a
      statistical analysis of the distribution of intersite spacing between adjacent
      CAD sites. Experimental tests confirm direct homodimeric interaction between CAD
      molecules as well as self-cooperative DNA binding by CAD. We note that
      computational modeling of the D. melanogaster CRMs alone did not yield
      significant evidence to support CAD self-cooperativity. We thus demonstrate how
      specific mechanistic details encoded in CRMs can be revealed by modeling their
      evolution and fitting such models to multispecies data. 

PMID- 24097307
TI  - A mechanistic pharmacodynamic model of IRAK-4 drug inhibition in the Toll-like
      receptor pathway.
AB  - The TLR pathway has been implicated in the pathogenesis of numerous diseases.
      IRAK-4 is integral to this pathway, making it a viable target for therapeutic
      intervention. This paper describes the application of a mechanistic
      pharmacodynamic model to assess the impact of IRAK-4 inhibition on the TLR-4
      pathway. The model uses a minimal number of rate equations, molecular species,
      and parameters to characterize TLR signal transduction biology, including ligand
      receptor interaction, protein complex formation, protein phosphorylation,
      negative regulation, and cytokine production. The model successfully reproduces
      the dynamic responses of TNFalpha to LPS stimulation, the tolerance to sequential
      LPS bolus dosing, the burst following a LPS bolus or infusion, and the modulation
      of pathway biomarkers following administration of an IRAK-4 inhibitor. Drug
      dosing schemes are evaluated for simulated disease states. The results emphasize
      the significance of LPS kinetics on response dynamics and the utility of a
      mechanistic model to help translate drug efficacy. 

PMID- 24097308
TI  - Tunable resistivity in magnetic glass phase of Gd(1-x)Ca(x)BaCo2O5.5.
AB  - We present magnetization and resistance measurements carried out on pristine and
      Ca-doped Gd(1-x)Ca(x)BaCo2O5.5 (x = 0.02) samples using the cooling and heating
      in unequal field (CHUF) protocol. The measurements reveal that the high
      temperature ferromagnetic phase is kinetically arrested at low temperature when
      the sample is cooled in a magnetic field. The volume fraction of this arrested
      phase increases upon Ca substitution and also by increasing the field in which
      the sample is cooled. Since the ferromagnetic phase is less resistive when
      compared to the low temperature antiferromagnetic phase, a tunable resistance is
      achieved in the sample by cooling in different magnetic fields. By cooling in
      magnetic fields of 9 T a reduction in resistivity by an order of magnitude is
      achieved. These results are consistent with the coexistence of the low
      temperature equilibrium antiferromagnetic phase with kinetically arrested high
      temperature ferromagnetic phase in the system.

PMID- 24097309
TI  - Pump up the volume - a central role for the plasma membrane H(+) pump in pollen
      germination and tube growth.
AB  - The plasma membrane H(+) ATPase is a member of the P-ATPase family transporting
      H(+) from the cytosol to the extracellular space and thus energizing the plasma
      membrane for the uptake of ions and nutrients. As a housekeeping gene, this
      protein can be detected in almost every plant cell including the exclusive
      expression of specific isoforms in pollen grains and tubes where its activity is
      a prerequisite for successful germination and growth of pollen tubes. This review
      summarizes the current knowledge on pollen PM H(+) ATPases and hypothesizes a
      central role for pollen-specific isoforms of this protein in tube growth.
      External as well as cytosolic signals from signal transduction and metabolic
      pathways are integrated by the PM H(+) ATPase and directly translated to tube
      growth rates, allocating the PM H(+) ATPase to an essential node in the
      signalling network of pollen tubes in their race to the ovule. 

PMID- 24097310
TI  - Filamin A protects cells against force-induced apoptosis by stabilizing talin-
      and vinculin-containing cell adhesions.
AB  - In mechanically loaded tissues such as weight-bearing joints, myocardium, and
      periodontal ligament, pathophysiological forces can disrupt cell-matrix contacts,
      which can induce cell death, leading to tissue and organ dysfunction. Protection
      against force-induced cell death may be mediated by filamin A (FLNa), an actin
      binding protein that regulates beta1 integrin-mediated cell adhesion. We examined
      the affect of filamin expression on collagen distribution and cell death in the
      periodontal ligament, a force-loaded tissue. Conditional deletion of FLNa in
      fibroblasts was associated with 2-fold increase of acellular areas in periodontal
      ligament and 7-fold higher proportions of apoptotic cells. In cultured
      fibroblasts with FLNa knockdown, we examined the affect of supraphysiological
      forces (1 pN/MUm(2) cell area; applied through the beta1 integrin) on recruitment
      of talin and vinculin to focal adhesions and on apoptosis. Compared with the wild
      type, FLNa-knockdown cells exhibited 3-fold increases in floating cells after
      overnight force application and a 2-fold increase in cell detachment. Force
      induced time-dependent reductions (P<0.05) in the numbers of activated beta1
      integrin-, talin-, and vinculin-stained adhesions in FLNa-knockdown compared with
      those in wild-type cells. We conclude that FLNa protects against apoptosis in
      force-loaded cells, and this protection is mediated by enhanced formation and
      maturation of matrix adhesions.

PMID- 24097311
TI  - Primary cilia respond to fluid shear stress and mediate flow-induced calcium
      deposition in osteoblasts.
AB  - Bone turnover in vivo is regulated by mechanical forces such as shear stress
      originating from interstitial oscillatory fluid flow (OFF), and bone cells in
      vitro respond to mechanical loading. However, the mechanisms by which bone cells
      sense mechanical forces, resulting in increased mineral deposition, are not well
      understood. The aim of this study was to investigate the role of the primary
      cilium in mechanosensing by osteoblasts. MLO-A5 murine osteoblasts were cultured
      in monolayer and subjected to two different OFF regimens: 5 short (2 h daily)
      bouts of OFF followed by morphological analysis of primary cilia; or exposure to
      chloral hydrate to damage or remove primary cilia and 2 short bouts (2 h on
      consecutive days) of OFF. Primary cilia were shorter and there were fewer cilia
      per cell after exposure to periods of OFF compared with static controls. Damage
      or removal of primary cilia inhibited OFF-induced PGE2 release into the medium
      and mineral deposition, assayed by Alizarin red staining. We conclude that
      primary cilia are important mediators of OFF-induced mineral deposition, which
      has relevance for the design of bone tissue engineering strategies and may inform
      clinical treatments of bone disorders causes by load-deficiency.

PMID- 24097312
TI  - Activation of virus uptake through induction of macropinocytosis with a novel
      polymerizing peptide.
AB  - A 27-aa peptide (P27) was previously shown to decrease the accumulation of human
      immunodeficiency virus type 1 (HIV-1) in the supernatant of chronically infected
      cells; however, the mechanism was not understood. Here, we show that P27 prevents
      virus accumulation by inducing macropinocytosis (MPC). Treatment of HIV-1- and
      human T-cell lymphotropic virus type 1 (HTLV-1)-infected cells with 2-10 MUM P27
      caused cell membrane ruffling and uptake of virus and polymerized forms of the
      peptide into large vacuoles. As demonstrated by electron microscopy, activation
      of MPC did not require virus or cells infected with virus, as P27 initiated its
      own uptake in the absence of virus. Inhibitors of MPC, Cytochalasin D and
      amiloride, decreased P27-mediated uptake of soluble dextran and inhibited P27
      induced virus uptake by >60%, which provides further evidence that P27 induces
      MPC. In CD4(+) HeLa cells, HIV-1 infection was enhanced by P27 up to 4-fold, and
      P27 increased infection at concentrations as low as 20 nM. The 5-aa C-terminal
      domain of P27 was necessary for virus uptake and may be responsible for the
      polymerization of P27 into fibrils. These forms of P27 may play a key role in
      triggering MPC, making this peptide a useful tool for studying virus uptake and
      infection, as well as MPC of other macromolecules.

PMID- 24097313
TI  - Cellular nanotechnology: making biological interfaces smarter.
AB  - Recently, there has been an outburst of research on engineered cell-material
      interfaces driven by nanotechnology and its tools and techniques. This tutorial
      review begins by providing a brief introduction to nanostructured materials,
      followed by an overview of the wealth of nanoscale fabrication and analysis tools
      available for their development. This background serves as the basis for a
      discussion of early breakthroughs and recent key developments in the endeavour to
      develop nanostructured materials as smart interfaces for fundamental cellular
      studies, tissue engineering and regenerative medicine. The review covers three
      major aspects of nanostructured interfaces - nanotopographical control, dynamic
      behaviour and intracellular manipulation and sensing - where efforts are
      continuously being made to further understand cell function and provide new ways
      to control cell behaviour. A critical reflection of the current status and future
      challenges are discussed as a conclusion to the review. 

PMID- 24097314
TI  - Comparison of different PADC materials for neutron dosimetry.
AB  - Investigations on track density and track size distributions of different PADC
      (poly allyl diglycol carbonate) materials have been performed. The PADC used for
      the tests has been produced by Thermo Electron (USA), Track Analysis System
      Limited (UK), Chiyoda Technol Corporation (Japan) and Intercast srl (Italy). For
      each PADC material 120 detectors were randomly selected out of 2 sheets: 60
      detectors from one sheet have been irradiated with a personal dose equivalent of
      3 mSv in the field of a (241)Am-Be source at the calibration laboratory of PSI,
      whilst the other 60 detectors from the other sheet have been used as background
      samples. All detectors have been processed according to an identical etching
      procedure and have been analysed with TASLImage scanning system. For each set of
      detectors the value of the average background signal, the average neutron
      sensitivity and the detection limit with respect to a personal dose equivalent
      measured with a dosemeter based on PADC have been determined. The results of the
      investigations allowed a comparison of the neutron sensitivity and background
      signal behaviours of PADC materials from different manufacturers and the
      assessment of the variation of neutron sensitivity and background signal over a
      single sheet. 

PMID- 24097315
TI  - [Mechanism of action for deep brain stimulation and electrical neuro-network
      modulation (ENM)].
AB  - Deep brain stimulation (DBS) has become an important treatment option for
      carefully screened medication resistant neurological and neuropsychiatric
      disorders. DBS therapy is not always applied deep to the brain; does not have to
      be applied exclusively to the brain; and the mechanism for DBS is not simply
      stimulation of structures. The applications and target locations for DBS devices
      are rapidly expanding, with many new regions of the brain, spinal cord,
      peripheral nerves, and muscles now possibly accessed through this technology. We
      will review the idea of "electrical neuro-network modulation (ENM)"; discuss the
      importance of the complex neural networks underpinning the effects of DBS;
      discuss the expansion of brain targets; discuss the use of fiber based targets;
      and discuss the importance of tailoring DBS therapy to the symptom, rather than
      the disease. 

PMID- 24097316
TI  - [A case of neuromyelitis optica spectrum disorder associated with a limited
      cutaneous systemic sclerosis and Sjogren syndrome].
AB  - A 51-year-old woman was referred to our department for a precise examination of
      her neuromyelitis optica spectrum disorder (NMOSD) symptoms. She had recurrent
      attacks of consciousness disturbance, cerebellar ataxia and diplopia (10 years
      ago), paraparesis and dysesthesia in four limbs (7 years ago), and consciousness
      disturbance and paraparesis (4 years ago). Neurological examination disclosed
      bilateral temporal pallor of the optic disc, atrophy and fasciculation of the
      right side of the tongue, dysesthesia in four limbs, mild motor weakness of both
      lower limbs, hyperreflexia in the right leg, pathological reflexes in bilateral
      lower limbs, and spastic bladder. T2-weighted cranial MRI showed lesions in the
      bilateral hypothalami and the dorsal portion of the medulla oblongata on the
      right side. T2-weighted spinal MRI revealed longitudinally extensive spinal cord
      lesions at T2-T8. A visual-evoked potential study disclosed prolonged latency of
      P100 bilaterally. During the examination, slight skin changes on the lower
      extremities indicative of scleroderma were observed, with no evidence of organ
      involvement. Skin biopsy showed increased numbers and swelling of collagen
      fibers. Thus, the patient was diagnosed with limited cutaneous systemic sclerosis
      (lcSSc). She also clinically manifested Sjogren syndrome. Her serum was positive
      for anti-nuclear, anti-centromere, and anti-aquaporin-4 antibodies. Following the
      administration of corticosteroids (25 mg/alternative day) the patient became
      stable. A variety of collagen diseases or autoimmune disorders have been reported
      to be major complications of NMOSD; however, the coexistence of lcSSc and NMOSD
      is extremely rare. To the best of our knowledge, this is the first description of
      a case with the coexistence of both conditions. Physicians should be aware of
      scleroderma in patients with NMOSD, even if patients do not complain of skin
      symptoms. 

PMID- 24097317
TI  - [Cerebral infarction and intracranial aneurysm related to the reactivation of
      varicella zoster virus in a Japanese acquired immunodeficiency syndrome (AIDS)
      patient].
AB  - A 35-years-old right-handed man admitted to our hospital with a worsening of
      dysarthria, left facial palsy and left hemiparesis for 2 days. Acquired
      immunodeficiency syndrome (AIDS) was diagnosed when he was 28 years old. At that
      time, he also was treated for syphilis. After highly active antiretroviral
      treatment (HAART) was introduced at the age of 35 years old, serum level of human
      immunodeficiency virus (HIV) was not detected, but the number of CD4+ T cells was
      still less than 200/MUl. He had no risk factors of atherosclerosis including
      hypertension, diabetes and hyperlipidemia. He had neither coagulation abnormality
      nor autoimmune disease. Magnetic resonance imaging (MRI) showed acute ischemic
      infarction spreading from the right corona radiate to the right internal capsule
      without contrast enhancement. Stenosis and occlusion of intracranial arteries
      were not detected by MR angiography. Although argatroban and edaravone were
      administered, his neurological deficits were worsened to be difficult to walk
      independently. Cerebrospinal fluid (CSF) examination showed a mild mononuclear
      pleocytosis (16/MUl). Oligoclonal band was positive. The titer of anti-varicella
      zoster virus (VZV) IgG antibodies was increased, that indicated VZV reactivation
      in the central nervous system (CNS), although VZV DNA PCR was not detected.
      Therefore, acyclovir (750 mg/day for 2 weeks) and valaciclovir (3,000 mg/day for
      1 month) were administered in addition to stroke therapy. He recovered to be able
      to walk independently 2 month after the admission.Angiography uncovered a
      saccular aneurysm of 3 mm at the end of branch artery of right anterior cerebral
      artery, Heubner artery, 28 days after the admission. We speculated that VZV
      vasculopathy caused by VZV reactivation in CNS was involved in the pathomechanism
      of cerebral infarction rather than HIV vasculopathy in the case.

PMID- 24097318
TI  - [A case of smoldering anti-leucine-rich glioma-inactivated 1 (LGI1) antibody
      associated limbic encephalitis with faciobrachial dystonic seizure].
AB  - We report a 59-year-old right-handed woman with smoldering leucine-rich glioma
      inactivated 1 (LGI1) antibody-associated limbic encephalitis (LE) following
      faciobrachial dystonic seizures. During 8 months before her admission, she
      developed partial seizures manifesting very brief and very frequent dystonia in
      her right hand sometimes with oral automatism and loss of awareness. In addition,
      she showed psychiatric disturbances such as emotionally labile condition and
      personality changes. On admission, neuropsychological examination revealed short
      term memory impairment. During electroencephalography (EEG) monitoring, ictal EEG
      showed rhythmic delta waves and interictal EEG showed intermittent irregular slow
      waves at the bilateral frontotemporal area. Brain MRI demonstrated high T2/FLAIR
      signal changes in the left amygdala expanding into the left hippocampus. FDG-PET
      showed hypermetabolism in the left amygdala, hippocampus and the bilateral basal
      ganglia. Cerebrospinal fluid analysis was unremarkable. There were no signs of
      malignant tumor detected on systemic examination. LGI1 antibody was positive in
      the serum and the cerebrospinal fluid and the clinical diagnosis of LGI1 antibody
      associated LE was confirmed. Her symptoms and the abnormalities in the brain
      MRI/FDG-PET showed immediate improvement after anti-epileptic and steroid
      therapy. 

PMID- 24097319
TI  - [Glioblastoma with ovarian teratoma having N-methyl-D-aspartate receptor (NMDAR)
      antibody in CSF--a case report].
AB  - A 54-year-old woman presented with complex partial seizure with impaired
      consciousness. Brain MRI revealed a high intensity lesion on T2-weighted and
      FLAIR images in the left temporal lobe, indicating limbic encephalitis. CT and
      MRI of the pelvis showed right ovarian teratoma. The cerebrospinal fluid (CSF)
      were positive for antibodies against the GluRepsilon2, GluRdelta2, and antibodies
      against NR1 + NR2B heteromers. On the basis of these data, anti-N-methyl-D
      aspartate receptor (NMDAR) encephalitis associated with ovarian teratoma was
      suspected, and the right ovariectomy was performed. Six months after onset, brain
      biopsy from the right temporal lobe led to a diagnosed of glioblastoma. This is
      the first glioblastoma case with ovarian teratoma having autoantibodies against
      GluR and NR1 + NR2B heteromers in CSF. We suggest that patients with NMDAR
      antibodies should be carefully diagnosed with anti-NMDAR encephalitis. 

PMID- 24097320
TI  - [Hashimoto's encephalopathy presenting periodic synchronous discharge, as a
      differential diagnosis for Creutzfeldt-Jakob disease].
AB  - Here, we report a case of Hashimoto's encephalopathy (HE) mimicking Creutzfeldt
      Jakob disease (CJD). A 57-year-old man was admitted to our hospital for status
      epilepticus. He had gradually presented personality change over the last two
      years. On admission, he was in state of akinetic mutism. He exhibited seizures on
      the left side of his body, including the face, and intermittent myoclonic
      movement. Routine laboratory tests showed no abnormalities, including thyroid
      functions. An EEG study showed typical periodic synchronous discharge (PSD).
      Brain MRI showed high-intensity areas in the bilateral frontal cortex, thalamus,
      and right insula on diffusion-weighted imaging (DWI). So, initially, sporadic CJD
      was suspected. However, there were no abnormalities in the caudate or putamen on
      MRI. Anti-TG and anti-TPO antibodies, as well as anti-NAE antibody were all
      positive. He was administered methylpredonisolone pulse therapy. Subsequently,
      his consciousness levels and EEG and MRI findings markedly improved. So, he was
      finally diagnosed with HE. HE should be considered in patients with PSD on EEG,
      even if the patients have typical MRI abnormalities of CJD. Anti-thyroid
      antibodies should be examined in such patients.

PMID- 24097321
TI  - [Reversible cerebral vasoconstriction syndrome (RCVS) triggered by nicotine
      patches].
AB  - We present a case of a patient with reversible cerebral vasoconstriction syndrome
      (RCVS) triggered by nicotine patches. A-50-year-old woman had no medical history
      and no regular medication. She smoked 20 cigarettes a day for 30 years. Six days
      after using nicotine patches, she had recurrent severe headaches of sudden onset
      (thunderclap headaches). On examination, the blood pressure was 142/88 mmHg. Her
      neurological and general examination, laboratory serum investigations, and
      cerebrospinal fluid examination were normal. Magnetic resonance imaging (MRI)
      including magnetic resonance angiography (MRA) on admission, day 10 after the
      first episode showed severe multifocal segmental narrowing of the bilateral
      posterior cerebral artery (PCA). Cessation of nicotine patches and administration
      of calcium-channel antagonist amlodipine 5 mg daily ameliorated her headache.
      Follow-up MRA, 37 days after the first episode, showed improvement of PCA
      stenosis. We diagnosed her as reversible cerebral vasoconstriction syndrome
      (RCVS) due to nicotine patches. It is important to recognize nicotine patches as
      a trigger of RCVS. 

PMID- 24097322
TI  - [A case of hypoglycemic coma with good outcome despite sustained unconsciousness
      and widespread leukoencephalopathy].
AB  - We described a 28-year-old woman with insulinoma-induced hypoglycemic coma. Her
      initial diffusion-weighted MRI revealed diffuse hyperintense lesions involving
      bilateral hemispheric white matter. She did not respond to the initial treatment
      with glucose. However, after surgical removal of insulinoma, she began to recover
      gradually, and 1 year later, returned to her previous work. In general, the
      outcome of hypoglycemic coma with widespread leukoencephalopathy on MRI is
      thought to be poor. However, we should be aware that some of such cases could
      recover in the long term. 

PMID- 24097323
TI  - [A Japanese SUNA patient with migraine without aura and medication overuse
      headache responsive to topiramate].
AB  - A 34-year-old woman presented with new intermittent short lasing headache around
      the left eye accompanied with lacrimation. She suffered from anemia and visual
      disturbance due to thalassaemia beta heterotype and retinitis pigmentosa. She
      also had continual cephalalgia from about 9 years old, and was taking
      nonsteroidal anti-inflammatory drug almost every day. After the medical
      treatment, we diagnosed her headache as migraine without aura, medication overuse
      headache (MOH) and short lasting unilateral neuralgiform headache attacks with
      cranial autonomic symptoms (SUNA). Triptan was effective for a migraine headache,
      but it was ineffective for attacks of SUNA, while topiramate dramatically reduced
      the SUNA attacks. A headache diary was effective to evaluate the clinical course
      and the effect of treatment for two different types of headaches by devising the
      approach to description. A migraine and MOH may coexist with SUNA, and our
      attention should be paid to the diagnosis and medical treatment in such cases. 

PMID- 24097324
TI  - [Bilateral sensorineural hearing impairment due to Streptococcus suis meningitis
      20 days after swine bite].
AB  - Streptococcus suis (S. suis) is a zoonotic pathogen in pigs, which can be
      transmitted to humans by close contact. Meningitis is the most common clinical
      manifestations of S. suis infection and hearing impairment is a frequent
      complication. The risk of S. suis meningitis is higher in people who work in the
      swine industry. The patient was a 53-year-old woman working in the swine
      industry, who developed headache and fever 20 days after a swine bite. She was
      diagnosed as meningitis and S. suis was detected in the cerebrospinal fluid. We
      treated her with ceftriaxone, vancomycin, and dexamethasone, and signs of
      meningeal irritation diminished three days after admission. However, bilateral
      sensorineural hearing impairment occurred on the ninth day after admission. We
      added methylprednisolone (500 mg, 2 days) but moderate hearing impairment
      remained on the left. Antibiotic therapy should be considered for wounds of
      people involved in the swine industry for preventing S. suis infection.When S.
      suis meningitis occurs, symptoms of hearing impairment must be monitored
      carefully. 

PMID- 24097331
TI  - Locally advanced prostate cancer: optimal therapy in older patients.
AB  - There is no standard treatment for locally advanced prostate cancer. Even the
      definition is still unclear. Locally advanced disease may refer to over-staged
      well-curable tumors as well as to advanced and probably incurable cancers.
      Similar uncertainties are present regarding the definition of 'old' in this
      context. Conservatively treated locally advanced prostate cancer is associated
      with poor survival outcome. With the increasing life expectancy, in the absence
      of curative treatment, even patients in their ninth decade of life may later
      suffer from symptoms of aggressive prostate cancer and are at a high risk of
      death from prostate cancer that might be prevented at least in part by early
      intervention. On the other hand, functional results after prostate cancer
      treatment are worse in elderly patients. In this article we discuss aspects of
      the management of locally advanced prostate cancer in the elderly with special
      focus on the recommendation of current clinical guidelines. 

PMID- 24097332
TI  - Targeted therapy for advanced hepatocellular cancer in the elderly: focus on
      sorafenib.
AB  - Hepatocellular carcinoma (HCC) is the third most common cause of cancer-related
      deaths worldwide. Worldwide progressive population aging demands consensus
      development for decision making when treating elderly patients. Age itself might
      not be a critical determinant for the selection of a therapeutic option. In the
      past few years, the mechanisms of hepato-carcinogenesis have been elucidated, and
      the involvement of a number of pathways, including angiogenesis, aberrant signal
      transduction, and dysregulated cell cycle control, have been demonstrated,
      leading to evaluation of the activity and toxicity of some of the new molecularly
      targeted agents. Sorafenib was demonstrated to significantly increase the
      survival of patients with advanced HCC in two prospective, randomized, placebo
      controlled trials. Subsequently, a number of retrospective or prospective studies
      have indicated that the effectiveness of sorafenib therapy in the treatment of
      HCC is similar in elderly and non-elderly patients. The aim of this review is to
      describe the impact of age on the effects of sorafenib-targeted therapy in
      patients with HCC, and the next treatment options with new targeted agents
      (everolimus, tivantinib, linifanib, etc.). 

PMID- 24097333
TI  - Lanthanide-IMAC enrichment of carbohydrates and polyols.
AB  - In this study a new type of immobilized metal ion affinity chromatography resin
      for the enrichment of carbohydrates and polyols was synthesized by radical
      polymerization reaction of vinyl phosphonic acid and 1,4-butandiole
      dimethacrylate using azo-bis-isobutyronitrile as radical initiator. Interaction
      between the chelated trivalent lanthanide ions and negatively charged hydroxyl
      groups of carbohydrates and polyols was observed by applying high pH values. The
      new method was evaluated by single standard solutions, mixtures of standards,
      honey and a more complex extract of Cynara scolymus. The washing step was
      accomplished by acetonitrile in excess volumes. Elution of enriched carbohydrates
      was successfully performed with deionized water. The subsequent analysis was
      carried out with matrix-free laser desorption/ionization-time of flight mass
      spectrometry involving a TiO2 -coated steel target, especially suitable for the
      measurement of low-molecular-weight substances. Quantitative analysis of the
      sugar alcohol xylitol as well as the determination of the maximal loading
      capacity was performed by gas chromatography in conjunction with mass
      spectrometric detection after chemical derivatization. In a parallel approach
      quantum mechanical geometry optimizations were performed in order to compare the
      coordination behavior of various trivalent lanthanide ions.

PMID- 24097334
TI  - Neuroprotective effects of rosmarinic acid on ciguatoxin in primary human
      neurons.
AB  - Ciguatoxin (CTX), is a toxic compound produced by microalgae (dinoflagellate)
      Gambierdiscus spp., and is bio-accumulated and bio-transformed through the marine
      food chain causing neurological deficits. To determine the mechanism of CTX
      mediated cytotoxicity in human neurons, we measured extracellular lactate
      dehydrogenase (LDH) activity, intracellular levels of nicotinamide adenine
      dinucleotide (NAD(+)) and H2AX phosphorylation at serine 139 as a measure for DNA
      damage in primary cultures of human neurons treated with Pacific (P)-CTX-1B and P
      CTX-3C. We found these marine toxins can induce a time and dose-dependent
      increase in extracellular LDH activity, with a concomitant decline in
      intracellular NAD(+) levels and increased DNA damage at the concentration range
      of 5-200 nM. We also showed that pre- and post-treatment with rosmarinic acid
      (RA), the active constituent of the Heliotropium foertherianum (Boraginaceae) can
      attenuate CTX-mediated neurotoxicity. These results further highlight the
      potential of RA in the treatment of CTX-induced neurological deficits. 

PMID- 24097336
TI  - U2AF1 mutations in primary myelofibrosis are strongly associated with anemia and
      thrombocytopenia despite clustering with JAK2V617F and normal karyotype.

PMID- 24097335
TI  - Food insecurity, socioeconomic status, and HIV-related risk behavior among women
      in farming households in Tanzania.
AB  - Food insecurity (FI) is associated with higher-risk sexual behavior in some
      studies. However, the overlap between FI and socioeconomic status (SES) has been
      poorly described. The study objectives were to: (1) determine the relationship
      between household FI and four dimensions of SES among sexually active Tanzanian
      women in farming households: expenditures, assets, flooring material of the home,
      and land ownership; and (2) determine whether FI is associated with higher-risk
      sexual behavior and relationship power. In male-headed households, FI was
      associated with assets, flooring material, and land ownership but not
      expenditures. There was no association between FI and the four dimensions of SES
      in female-headed households. Among women in male-headed households, but not
      female household heads themselves, severe FI was associated with a non
      significant increase in the likelihood of being in a relationship because of
      material goods [adjusted prevalence ratio (PRa) = 1.76, 95 % confidence interval
      (CI) 0.81, 3.81] and was inversely associated with being able to ask partners to
      use condoms (PRa = 0.47, 95 % CI 0.25, 0.88). There was not a strong association
      between food security and relationship power. Our findings suggest that the
      association between FI and HIV risk behavior may differ depending on the type of
      household.

PMID- 24097337
TI  - Delineating MEIS1 cis-regulatory elements active in hematopoietic cells.

PMID- 24097338
TI  - EZH2 in normal and malignant hematopoiesis.
AB  - The histone methyltransferase Enhancer of Zeste Homologue 2 (EZH2), a component
      of the polycomb group complex, is vital for stem cell development, including
      hematopoiesis. Its primary function, to deposit the histone mark H3K27me3,
      promotes transcriptional repression. The activity of EZH2 influences cell fate
      regulation, namely the balance between self-renewal and differentiation. The
      contribution of aberrant EZH2 expression to tumorigenesis by directing cells
      toward a cancer stem cell (CSC) state is increasingly recognized. However, its
      role in hematological malignancies is complex. Point mutations, resulting in gain
      of-function, and inactivating mutations, reported in lymphoma and leukemia,
      respectively, suggest that EZH2 may serve a dual purpose as an oncogene and tumor
      suppressor gene. The reduction of CSC self-renewal via EZH2 inhibition offers a
      potentially attractive therapeutic approach to counter the aberrant activation
      found in lymphoma and leukemia. The discovery of small molecules that
      specifically inhibit EZH2 raises the exciting possibility of exploiting the
      oncogenic addiction of tumor cells toward this protein. However, interference
      with the tumor-suppressor role of wild-type EZH2 must be avoided. This review
      examines the role of EZH2 in normal and malignant hematopoiesis and recent
      developments in harnessing the therapeutic potential of EZH2 inhibition. 

PMID- 24097340
TI  - Levobupivacaine vs. bupivacaine for third molar surgery: quality of anaesthesia,
      postoperative analgesia and local vascular effects.
AB  - OBJECTIVES: The main purpose of this prospective, double-blind, randomized study
      was to evaluate anaesthetic parameters, postoperative analgesia and vasoactive
      properties of levobupivacaine and bupivacaine for lower third molar surgery.
      MATERIAL AND METHODS: Sixty patients (ASA I) were scheduled for lower third molar
      surgery under inferior alveolar nerve block, lingual nerve block and buccal nerve
      block (mandibular nerve blocks) obtained with 3 ml of 0.5 % levobupivacaine and 3
      ml of 0.5 % bupivacaine. Success rate, onset and duration of three nerve bocks
      were evaluated by electrical pulp testing, pinprick testing and signs of soft
      tissue anaesthesia (patient-reported numbness). Intensity of intraoperative
      anaesthesia and postoperative analgesia were measured with visual analogue scale
      (VAS) and numeric rating scale (NRS). The time of first postoperative pain
      reported and analgesic consumption were also recorded. The laser Doppler
      flowmetry was used for the measurement of the first premolar pulpal blood flow.
      RESULTS: There were no differences between levobupivacaine and bupivacaine
      regarding the success rate, onset and duration of mandibular nerve blocks as well
      as intensity of postoperative analgesia and analgesic consumption. Intensity of
      intraoperative anaesthesia and duration of postoperative analgesia were
      significantly higher in the levobupivacaine than in the bupivacaine group. Both
      anaesthetics showed similar biphasic vasoactive effect. CONCLUSIONS:
      Levobupivacaine 0.5 % achieved superiority over bupivacaine 0.5 % in the
      intensity of intraoperative anaesthesia and duration of postoperative analgesia
      for lower third molar surgery under the mandibular nerve blocks. CLINICAL
      RELEVANCE: It seems that the plain levobupivacaine (0.5 %) could be an effective
      alternative to plain bupivacaine (0.5 %) in those dental procedures which require
      profound bone and soft tissue anaesthesia.

PMID- 24097339
TI  - Midbrain dopamine function in schizophrenia and depression: a post-mortem and
      positron emission tomographic imaging study.
AB  - Elevated in vivo markers of presynaptic striatal dopamine activity have been a
      consistent finding in schizophrenia, and include a large effect size elevation in
      dopamine synthesis capacity. However, it is not known if the dopaminergic
      dysfunction is limited to the striatal terminals of dopamine neurons, or is also
      evident in the dopamine neuron cell bodies, which mostly originate in the
      substantia nigra. The aim of our studies was therefore to determine whether
      dopamine synthesis capacity is altered in the substantia nigra of people with
      schizophrenia, and how this relates to symptoms. In a post-mortem study, a semi
      quantitative analysis of tyrosine hydroxylase staining was conducted in nigral
      dopaminergic cells from post-mortem tissue from patients with schizophrenia (n =
      12), major depressive disorder (n = 13) and matched control subjects (n = 13). In
      an in vivo imaging study, nigral and striatal dopaminergic function was measured
      in patients with schizophrenia (n = 29) and matched healthy control subjects (n =
      29) using (18)F-dihydroxyphenyl-L-alanine ((18)F-DOPA) positron emission
      tomography. In the post-mortem study we found that tyrosine hydroxylase staining
      was significantly increased in nigral dopaminergic neurons in schizophrenia
      compared with both control subjects (P < 0.001) and major depressive disorder (P
      < 0.001). There was no significant difference in tyrosine hydroxylase staining
      between control subjects and patients with major depressive disorder, indicating
      that the elevation in schizophrenia is not a non-specific indicator of
      psychiatric illness. In the in vivo imaging study we found that (18)F
      dihydroxyphenyl-L-alanine uptake was elevated in both the substantia nigra and in
      the striatum of patients with schizophrenia (effect sizes = 0.85, P = 0.003 and
      1.14, P < 0.0001, respectively) and, in the voxel-based analysis, was elevated in
      the right nigra (P < 0.05 corrected for family wise-error). Furthermore, nigral
      (18)F-dihydroxyphenyl-L-alanine uptake was positively related with the severity
      of symptoms (r = 0.39, P = 0.035) in patients. However, whereas nigral and
      striatal (18)F-dihydroxyphenyl-L-alanine uptake were positively related in
      control subjects (r = 0.63, P < 0.001), this was not the case in patients (r =
      0.30, P = 0.11). These findings indicate that elevated dopamine synthesis
      capacity is seen in the nigral origin of dopamine neurons as well as their
      striatal terminals in schizophrenia, and is linked to symptom severity in
      patients.

PMID- 24097341
TI  - The necessity of a test reading after 1 week to detect late positive patch test
      reactions in patients with oral lichen lesions.
AB  - OBJECTIVES: Establishing the clinical relevance of contact allergy to dental
      materials in patients with oral lichen lesions (OLL) may be difficult, and tests
      are often read only on day 3 or day 4; also, concentration of the tested
      allergens may vary. Several studies on dermatitis patients have shown that
      additional positive patch test reactions can be found after day 4. Therefore, the
      aim of the present study was to analyse the frequency of late positive reactions
      to potential allergens in patients with OLL. MATERIAL AND METHODS: Eighty-three
      of 96 consecutive patients with biopsy-verified OLL were patch-tested with a
      recently developed lichen series. The patches were removed after 48 h and
      reactions read 3 and 7 days after application. RESULTS: A total of 129 contact
      allergies were found, and 26 (20.2 %) of the allergic reactions in 23 patients
      were seen on day 7 only. The 25.2 % increase in positive test reactions with an
      additional reading on day 7 in addition to day 3 was statistically significant.
      Metals were the substances with the highest frequency of late positive reactions.
      CONCLUSIONS: Patients with OLL cannot be considered properly investigated with
      regard to contact allergy, unless the testing has been performed with mandatory
      readings on day 3 (or day 4) and day 7. CLINICAL RELEVANCE: Late patch test
      readings are crucial in order to elucidate the role of contact allergy to dental
      materials in the aetiology of OLL.

PMID- 24097342
TI  - Electronic structure and the magneto-caloric effect.
AB  - We present a theoretical investigation of the entropy changes upon the
      application of an external field leading to the magneto-caloric effect (MCE). The
      case of localized magnetic moments is treated within the Weiss molecular field
      model, but special emphasis is given to cases of itinerant electron magnetism.
      These are described within the Landau theory of phase transitions and the
      temperature dependence is included via spin fluctuations. Since the parameters of
      the Landau expansion can be calculated from first-principles calculations of the
      electronic and magnetic structure, an immediate connection to the electronic band
      structure and its properties becomes possible. We study ordinary ferromagnets,
      including magneto-volume coupling and itinerant electron metamagnets, where in a
      small external field range large changes of the magnetic moments occur. We find
      that such metamagnetic systems are the most promising candidates for a large MCE
      in itinerant electron systems. We apply our expressions to several transition
      metals and their alloys, as well as to the metamagnets YCo2 and Fe2P, and find
      reasonable agreement with available experimental data. 

PMID- 24097343
TI  - Chemically grown vertically aligned 1D ZnO nanorods with CdS coating for
      efficient quantum dot sensitized solar cells (QDSSC): a controlled synthesis
      route.
AB  - In the present article, vertically aligned ZnO nanorod arrays were synthesized by
      an aqueous chemical growth (ACG) route on a fluoride doped tin oxide (FTO) coated
      glass substrate. These nanorods were further sensitized with cadmium sulfide
      (CdS) quantum dots (QDs) by a successive ionic layer adsorption and reaction
      (SILAR) technique. The synthesized CdS coated ZnO nanorods were characterized for
      their structural and morphological properties with X-ray diffraction (XRD), high
      resolution transmission electron microscopy (HRTEM), X-ray photoelectron
      spectroscopy (XPS) and field emission scanning electron microscopy (FESEM).
      Finally, prepared CdS coated 1D ZnO photoelectrodes were tested for their
      photoelectrochemical performance. Our results show that the sample deposited
      after 40 SILAR cycles shows 5.61 mA cm(-2) short current density (JSC) with eta =
      1.61% power conversion efficiency. 

PMID- 24097344
TI  - Experience of an eating disorders out-patient program in an internal medicine
      hospital.
AB  - PURPOSE: The aim of this study was to develop a successful low budget out-patient
      program, in an internal medicine hospital, for patients presenting eating
      disorders in an emerging nation. METHODS: A total of 144 patients were included
      in a 6 month intervention centered in medical support, with fortnightly medical
      consultations, monthly counseling by a nutritionist and by a psychiatrist and
      three psycho-educational courses. The Three Factor Eating Questionnaire and the
      Eating Disorders Inventory-2 were performed at the beginning and at the end of
      the study. RESULTS: After 6 months, more than half of the patients who completed
      the intervention were on remission. Substantial improvement was observed
      regarding the scores of both instruments after completion of the program.
      CONCLUSIONS: The outcome of this study compares favorably to previous published
      data of more intensive programs. These results were obtained having little
      infrastructure, a low budget and limited human resources, making this a suitable
      eating disorders program for emerging nations.

PMID- 24097345
TI  - Tracking of weight status and body fatness in Italian children.
AB  - The prevalence of weight disorders among school-aged children is an increasing
      phenomenon and it is of great importance to identify the characteristics of
      individuals at risk of gaining or retaining weight. This study aimed to examine
      the prevalence of weight disorders and their tracking over a 3-year period in a
      sample of Italian children. Body mass, body height and selected skinfold
      thicknesses were assessed in 355 children at the age of 7 and 10 years. Tracking
      of body mass index (BMI), inverted BMI (iBMI) and skinfold-based body fat were
      analyzed and the relationships between changes in BMI and body fat were examined.
      Children presenting with overweight or obesity at 7 years old showed a trend
      toward lower weight categories at 10 years old. Conversely, a trend to become
      overweight was observed among normal weight boys, and a trend to become
      underweight was observed among normal weight girls. BMI, iBMI and body fat showed
      good levels of tracking, with high correlations between measurements performed at
      7 and 10 years of age. Furthermore, BMI and iBMI changes were correlated to body
      fatness changes. The present study shows the importance of carefully following
      children's development over time because weight disorders may appear even in
      previously normal weight children. 

PMID- 24097346
TI  - Critical comments concerning shape and weight: associations with eating
      psychopathology among full-time dance students.

PMID- 24097347
TI  - Interface superconductor with gap behaviour like a high-temperature
      superconductor.
AB  - The physics of the superconducting state in two-dimensional (2D) electron systems
      is relevant to understanding the high-transition-temperature copper oxide
      superconductors and for the development of future superconductors based on
      interface electron systems. But it is not yet understood how fundamental
      superconducting parameters, such as the spectral density of states, change when
      these superconducting electron systems are depleted of charge carriers. Here we
      use tunnel spectroscopy with planar junctions to measure the behaviour of the
      electronic spectral density of states as a function of carrier density,
      clarifying this issue experimentally. We chose the conducting LaAlO3-SrTiO3
      interface as the 2D superconductor, because this electron system can be tuned
      continuously with an electric gate field. We observed an energy gap of the order
      of 40 microelectronvolts in the density of states, whose shape is well described
      by the Bardeen-Cooper-Schrieffer superconducting gap function. In contrast to the
      dome-shaped dependence of the critical temperature, the gap increases with charge
      carrier depletion in both the underdoped region and the overdoped region. These
      results are analogous to the pseudogap behaviour of the high-transition
      temperature copper oxide superconductors and imply that the smooth continuation
      of the superconducting gap into pseudogap-like behaviour could be a general
      property of 2D superconductivity. 

PMID- 24097348
TI  - alphaTAT1 catalyses microtubule acetylation at clathrin-coated pits.
AB  - In most eukaryotic cells microtubules undergo post-translational modifications
      such as acetylation of alpha-tubulin on lysine 40, a widespread modification
      restricted to a subset of microtubules that turns over slowly. This subset of
      stable microtubules accumulates in cell protrusions and regulates cell
      polarization, migration and invasion. However, mechanisms restricting acetylation
      to these microtubules are unknown. Here we report that clathrin-coated pits
      (CCPs) control microtubule acetylation through a direct interaction of the alpha
      tubulin acetyltransferase alphaTAT1 (refs 8, 9) with the clathrin adaptor AP2. We
      observe that about one-third of growing microtubule ends contact and pause at
      CCPs and that loss of CCPs decreases lysine 40 acetylation levels. We show that
      alphaTAT1 localizes to CCPs through a direct interaction with AP2 that is
      required for microtubule acetylation. In migrating cells, the polarized
      orientation of acetylated microtubules correlates with CCP accumulation at the
      leading edge, and interaction of alphaTAT1 with AP2 is required for directional
      migration. We conclude that microtubules contacting CCPs become acetylated by
      alphaTAT1. In migrating cells, this mechanism ensures the acetylation of
      microtubules oriented towards the leading edge, thus promoting directional cell
      locomotion and chemotaxis. 

PMID- 24097349
TI  - Structural insight into magnetochrome-mediated magnetite biomineralization.
AB  - Magnetotactic bacteria align along the Earth's magnetic field using an organelle
      called the magnetosome, a biomineralized magnetite (Fe(II)Fe(III)2O4) or greigite
      (Fe(II)Fe(III)2S4) crystal embedded in a lipid vesicle. Although the need for
      both iron(II) and iron(III) is clear, little is known about the biological
      mechanisms controlling their ratio. Here we present the structure of the
      magnetosome-associated protein MamP and find that it is built on a unique
      arrangement of a self-plugged PDZ domain fused to two magnetochrome domains,
      defining a new class of c-type cytochrome exclusively found in magnetotactic
      bacteria. Mutational analysis, enzyme kinetics, co-crystallization with iron(II)
      and an in vitro MamP-assisted magnetite production assay establish MamP as an
      iron oxidase that contributes to the formation of iron(III) ferrihydrite
      eventually required for magnetite crystal growth in vivo. These results
      demonstrate the molecular mechanisms of iron management taking place inside the
      magnetosome and highlight the role of magnetochrome in iron biomineralization.

PMID- 24097350
TI  - Molecular understanding of sulphuric acid-amine particle nucleation in the
      atmosphere.
AB  - Nucleation of aerosol particles from trace atmospheric vapours is thought to
      provide up to half of global cloud condensation nuclei. Aerosols can cause a net
      cooling of climate by scattering sunlight and by leading to smaller but more
      numerous cloud droplets, which makes clouds brighter and extends their lifetimes.
      Atmospheric aerosols derived from human activities are thought to have
      compensated for a large fraction of the warming caused by greenhouse gases.
      However, despite its importance for climate, atmospheric nucleation is poorly
      understood. Recently, it has been shown that sulphuric acid and ammonia cannot
      explain particle formation rates observed in the lower atmosphere. It is thought
      that amines may enhance nucleation, but until now there has been no direct
      evidence for amine ternary nucleation under atmospheric conditions. Here we use
      the CLOUD (Cosmics Leaving OUtdoor Droplets) chamber at CERN and find that
      dimethylamine above three parts per trillion by volume can enhance particle
      formation rates more than 1,000-fold compared with ammonia, sufficient to account
      for the particle formation rates observed in the atmosphere. Molecular analysis
      of the clusters reveals that the faster nucleation is explained by a base
      stabilization mechanism involving acid-amine pairs, which strongly decrease
      evaporation. The ion-induced contribution is generally small, reflecting the high
      stability of sulphuric acid-dimethylamine clusters and indicating that galactic
      cosmic rays exert only a small influence on their formation, except at low
      overall formation rates. Our experimental measurements are well reproduced by a
      dynamical model based on quantum chemical calculations of binding energies of
      molecular clusters, without any fitted parameters. These results show that, in
      regions of the atmosphere near amine sources, both amines and sulphur dioxide
      should be considered when assessing the impact of anthropogenic activities on
      particle formation. 

PMID- 24097351
TI  - Spatial organization within a niche as a determinant of stem-cell fate.
AB  - Stem-cell niches in mammalian tissues are often heterogeneous and
      compartmentalized; however, whether distinct niche locations determine different
      stem-cell fates remains unclear. To test this hypothesis, here we use the mouse
      hair follicle niche and combine intravital microscopy with genetic lineage
      tracing to re-visit the same stem-cell lineages, from their exact place of
      origin, throughout regeneration in live mice. Using this method, we show directly
      that the position of a stem cell within the hair follicle niche can predict
      whether it is likely to remain uncommitted, generate precursors or commit to a
      differentiated fate. Furthermore, using laser ablation we demonstrate that hair
      follicle stem cells are dispensable for regeneration, and that epithelial cells,
      which do not normally participate in hair growth, re-populate the lost stem-cell
      compartment and sustain hair regeneration. This study provides a general model
      for niche-induced fate determination in adult tissues. 

PMID- 24097353
TI  - Synthesis and characterization of phosphine-(thio)phenolate-based half
      zirconocenes and their application in ethylene (co-)polymerization.
AB  - A series of novel half-zirconocenes containing phosphine-(thio)phenolate
      chelating ligands of the type Cp'Zr(thf)Cl2[X-2-R(1)-4-R(2)-6-(PPh2)C6H2] (Cp' =
      C5Me5, 2a: X = O, R(1) = Ph, R(2) = H; 2b: X = O, R(1) = (t)Bu, R(2) = H; 2c: X =
      O, R(1) = R(2) = (t)Bu; 2d: X = O, R(1) = SiMe3, R(2) = H; 2e: X = S, R(1) =
      SiMe3, R(2) = H; Cp' = C5H5, 3b: X = O, R(1) = (t)Bu, R(2) = H; 3c: X = O, R(1) =
      R(2) = (t)Bu; 3d: X = O, R(1) = SiMe3, R(2) = H; 3e: X = S, R(1) = SiMe3, R(2) =
      H) have been synthesized in high yields (74-85%). These complexes were identified
      by (1)H, (13)C and (31)P NMR as well as elemental analyses. Structural analysis
      for 2a-b and 2d revealed that these complexes adopt six-coordinate, distorted
      octahedral geometry around the zirconium center. These novel half-zirconocenes
      possessed high catalytic performance for ethylene polymerization at high
      temperature in the presence of MMAO. The phosphine-phenolate-based Cp* complexes
      produced high molecular weight polymers (M(W) > 400,000), while the Cp analogues
      displayed much higher activities at high temperature. Complex 3c with MMAO showed
      a maximum ethylene polymerization activity of 17,580 kg mol(Zr)(-1) h(-1) at 75 
      degrees C. In addition, the Cp based complexes 3b-e could promote ethylene and 1
      hexene copolymerization with high activities.

PMID- 24097352
TI  - Cortical interneurons that specialize in disinhibitory control.
AB  - In the mammalian cerebral cortex the diversity of interneuronal subtypes
      underlies a division of labour subserving distinct modes of inhibitory control. A
      unique mode of inhibitory control may be provided by inhibitory neurons that
      specifically suppress the firing of other inhibitory neurons. Such disinhibition
      could lead to the selective amplification of local processing and serve the
      important computational functions of gating and gain modulation. Although several
      interneuron populations are known to target other interneurons to varying
      degrees, little is known about interneurons specializing in disinhibition and
      their in vivo function. Here we show that a class of interneurons that express
      vasoactive intestinal polypeptide (VIP) mediates disinhibitory control in
      multiple areas of neocortex and is recruited by reinforcement signals. By
      combining optogenetic activation with single-cell recordings, we examined the
      functional role of VIP interneurons in awake mice, and investigated the
      underlying circuit mechanisms in vitro in auditory and medial prefrontal
      cortices. We identified a basic disinhibitory circuit module in which activation
      of VIP interneurons transiently suppresses primarily somatostatin- and a fraction
      of parvalbumin-expressing inhibitory interneurons that specialize in the control
      of the input and output of principal cells, respectively. During the performance
      of an auditory discrimination task, reinforcement signals (reward and punishment)
      strongly and uniformly activated VIP neurons in auditory cortex, and in turn VIP
      recruitment increased the gain of a functional subpopulation of principal
      neurons. These results reveal a specific cell type and microcircuit underlying
      disinhibitory control in cortex and demonstrate that it is activated under
      specific behavioural conditions. 

PMID- 24097354
TI  - Hepatoprotective role of Nicotiana plumbaginifolia Linn. against carbon
      tetrachloride-induced injuries.
AB  - Nicotiana plumbignifolia (Linn) is used as folk medicine in the treatment of
      liver dysfunction in Pakistan. The present study was designed to investigate the
      hepatoprotective role of N. plumbignifolia methanolice extract (NPME) against
      carbon tetrachloride (CCl4)-induced oxidative damage in liver of chicks.
      Methanolic extract of N. plumbignifolia was obtained and was further evaluated as
      a hepatoprotective agent against CCl4-induced oxidative damage in liver of
      chicks. For this study, 60-day-old 50 male chicks were divided into five groups.
      Chicks of group 1 (control) had free access to food and water. Group II received
      1 mL/kg of CCl4 (30% in olive oil v/v) via the intraperitoneal route thrice a
      week for 4 weeks. Group III received 100 mg/kg body weight (b.w.) of silymarin
      via gavage after 48 h of CCl4 treatment, whereas group IV were given 200 mg/kg
      b.w. NPME after 48 h of CCl4 treatment. Hepatoprotective activity was assessed by
      measuring the activities of the antioxidant enzymes: catalase, peroxidase,
      superoxide dismutase, glutathione peroxidase, glutathione reductase, and lipid
      peroxidation (thiobarbituric acid reactive substances (TBARS)). Serum was
      analyzed for various biochemical parameters. The results revealed that CCl4
      induced oxidative stress as evidenced by the significant decrease in the activity
      levels of antioxidant enzymes, while an increase in the levels of TBARS in liver
      samples is compared with the control group. Serum levels lactate dehydrogenase,
      triglycerides, total cholesterol, and low-density lipoprotein was elevated while
      reducing high-density lipoprotein compared to controls. Cotreatment of NPME
      treatment reversed these alterations, which seems likely that NPME can protect
      the liver tissues against CCl4-mediated oxidative damage.

PMID- 24097355
TI  - Antioxidant status in oral subchronic toxicity of fipronil and fluoride co
      exposure in buffalo calves.
AB  - The effects of fipronil and fluoride co-exposure were investigated on antioxidant
      status of buffalo calves. A total of 24 healthy male buffalo calves divided into
      4 groups were treated for 98 consecutive days. Group I, receiving no treatment,
      served as the control. Animals of groups II and III were orally administered with
      fipronil at the dosage of 0.5 mg/kg/day and sodium fluoride (NaF) at the dosage
      of 6.67 mg/kg/day, respectively, for 98 days. Group IV was coadministered with
      fipronil and NaF at the same dosages as groups II and III. Administration of
      fipronil alone produced significant elevation in lipid peroxidation (LPO) and
      decrease in the levels of nonenzymatic antioxidant glutathione (GSH). However, it
      did not produce any significant effect on the activities of enzymatic
      antioxidants including glutathione peroxidase (GPx), catalase (CAT), and
      superoxide dismutase (SOD). NaF exposure led to enhanced oxidative stress as
      shown by significant increase in the LPO and SOD activities while GPx and CAT
      activities and GSH levels were significantly decreased. Co-exposure to fipronil
      and NaF showed additive effects on LPO, GPx activity, and GSH levels.

PMID- 24097356
TI  - Histopathological alterations after a growth promoter boldenone injection in
      rabbits.
AB  - Boldenone (BOL) is a derivative of the testosterone that has dual effects on
      humans, both directly and indirectly; directly as injection to build muscles and
      indirectly as through consuming meat of animals that where treated with BOL.
      However, the action of these steroids on different body organs structures is
      still unclear; therefore, the aim of the present study was to investigate the
      effect of the intramuscular injection of BOL undecylenate on the different organ
      structures. A total of 10 adult New Zealand rabbits were divided into two main
      groups, the first group was the control group, which includes animals that were
      injected intramuscularly with olive oil and the second group included animals
      that received two intramuscular injections of 5 mg/kg body weight BOL dissected
      after 6 weeks. Our results showed that intramuscular injection of rabbits with
      BOL showed hypertrophy in both skeletal and cardiac muscles, disturbances of the
      hepatocytes radially arranged cords with multifocal hepatocellular vacuolations
      in the liver, glomerulus mass reduction with multifocal glomerular injury in the
      kidney, disturbances of the cycle of spermatogenesis in the testes. In
      conclusion, using BOL, while preparing for a young bodybuilding contest, may
      cause an alteration in the histological structure of most of the body organs;
      these findings suggested that especially young people who misuse anablic
      androgenic steroids should be careful if they want to use such steroids to
      enhance their strength and endurance.

PMID- 24097357
TI  - The potential chemoprotective effects of melatonin against genotoxicity induced
      by diazinon in human peripheral blood lymphocytes.
AB  - The protection afforded by melatonin (MLT) against diazinon (DZN)-induced
      micronucleus formation, an index of DNA damage, in human blood lymphocytes was
      investigated. Whole blood samples were collected from five volunteers and were
      incubated with MLT at different concentrations (100, 200, 300, and 400 uM final
      concentration) for 1 h. The samples were then incubated with 750 uM DZN for 1 h.
      Subsequently, the lymphocytes were cultured with a mitogenic stimulant to
      evaluate micronucleus formation in cytokinesis-blocked binucleated cells. The
      incubation of lymphocytes with DZN induces additional genotoxicity. Pretreatment
      with MLT at these doses significantly reduced the micronucleus frequency in
      cultured lymphocytes (p < 0.05-p < 0.0001). The maximum decrease in the frequency
      of micronuclei was observed at 400 uM of MLT, which caused a reduction of 87%.
      MLT also exhibited an excellent and dose-dependent radical-scavenging activity
      against 1,1-diphenyl-2-picrylhydrazyl free radicals. Our study revealed that MLT
      has a potent antigenotoxic effect against DZN-induced DNA damage, which may be
      due to the scavenging of free radicals and increased antioxidant status. Because
      MLT is a natural compound and is considered safe, it can be used as a supplement
      to protect people exposed to chemical or environmental hazards.

PMID- 24097358
TI  - Antitumor characterization of various fractions of Launaea procumbens.
AB  - The antitumor activity of various six fractions of Launaea procumbens were
      studied using the potato disk bioassay technique. Three concentrations (10, 100,
      and 1000 ppm) of all these six fractions were used for characterization of
      antitumor activity. Among these fractions, methanolic fraction exhibited
      significant inhibition of crown gall tumors caused by Agrobacterium tumefaciens
      followed by butanolic fraction. These results revealed that methanolic and
      butanolic fractions contain bioactive constituents responsible for inhibition of
      tumor. Further purification and characterization are in progress in our
      laboratory. 

PMID- 24097359
TI  - Vanadium inhalation induces actin changes in mice testicular cells.
AB  - Infertility is becoming a health problem, which has increased mainly in
      megacities, and several studies have shown its association with environmental
      pollution. Air pollution has been linked to alterations in sperm parameters, both
      in humans and animal models. In male humans, it has been associated with reduced
      semen quality and DNA alterations. Vanadium is a transition element that has
      increased in recent decades as a component of air suspended matter and has been
      associated with reprotoxic effects in animal models. Few are the mechanisms
      described by which the vanadium produces these effects, and cytoskeleton
      interaction is a possibility. We reported immunohistochemical changes in actin
      testicular cytoskeleton in a vanadium inhalation experimental mice model. Our
      findings show that exposure to vanadium pentoxide (0.02 M) results in actin
      decrease in testicular cells from 3-12 weeks exposure time; this effect was
      statistically significant and exposure time dependent. Actin cytoskeleton damage
      is a mechanism that could explain vanadium reprotoxic effects and its association
      with impaired fertility.

PMID- 24097360
TI  - Studies on fate and toxicity of nanoalumina in male albino rats: Lethality,
      bioaccumulation and genotoxicity.
AB  - The purpose of this study is to follow-up the distribution, lethality percentile
      doses (LDs) and bioaccumulation of aluminium oxide nanoparticles (Al2O3-NPs,
      average diameter 9.83 +/- 1.61 nm) in some tissues of male albino rats, and to
      evaluate its genotoxicity to the brain tissues, during acute and sublethal
      experiments. The LDs of Al2O3-NPs, including median lethal dose (LD50), were
      estimated after intraperitoneal injection. The computed LD50 at 24 and 48 h were
      15.10 and 12.88 g/kg body weight (b.w.), respectively. For acute experiments, the
      bioaccumulation of aluminium (Al) in the brain, liver, kidneys, intestine and
      spleen was estimated after 48 h of injection with a single acute dose (3.9, 6.4
      and 8.5 g/kg b.w.), while for sublethal experiments it was after 1, 3, 7, 14 and
      28 days of injection with 1.3 g/kg b.w. once in 2 days. Multi-way analysis of
      variance affirmed that Al uptake, in acute experiments, was significantly
      affected by the injected doses, organs (brain, liver, kidneys, intestine and
      spleen) and their interactions, while for sublethal experiments an altogether
      effect based on time (1, 3, 7, 14, 28 days), doses (0 and 1.3 g), organs and
      their interactions was reported. In addition, Al accumulated in the brain, liver,
      kidney, intestine and spleen of rats administered with Al2O3-NPs were
      significantly higher than the corresponding controls, during acute and sublethal
      experiments. The uptake of Al by the spleen of rats injected with acute doses was
      greater than that accumulated by kidney>brain>intestine>liver, whereas the brain
      of rats injected with sublethal dose accumulated lesser amount of Al followed by
      the kidney<intestine<spleen<liver. Bioaccumulation of Al, in all studied tissues,
      was positively correlated with the injected doses (in acute term) and the
      experimental periods (in sublethal term). In the acute and sublethal experiments,
      comet assay parameters such as the tail intensity (i.e. DNA percentage), tail
      extent moment and olive tail moment were estimated using a single cell gel
      electrophoresis/comet assay. The results showed significant increase in DNA
      percentage damage in the brain cells. The obtained results indicate that
      bioaccumulation of Al was associated with significantly increased levels of comet
      parameters that depended on the doses and the experimental periods. In
      conclusion, Al has a high affinity to get accumulated in tissues to a level that
      is able to induce genotoxicity. Therefore, bioaccumulation is time, dose and
      organ dependant.

PMID- 24097361
TI  - Antibacterial effects of curcumin: An in vitro minimum inhibitory concentration
      study.
AB  - AIM: To evaluate the antibacterial effect of curcumin with the minimum inhibitory
      concentration (MIC) method in standard bacterial strains. METHODS: The in vitro
      antibacterial activity of curcumin was evaluated against methicillin-sensitive
      Staphylococcus aureus (MSSA) (ATCC 29213), methicillin-resistant Staphylococcus
      aureus (MRSA) (ATCC 43300), Enterococcus faecalis (ATCC 29212), Bacillus subtilis
      (ATCC 6633), Pseudomonas aeruginosa (ATCC 27853), Escherichia coli (ATCC 25922)
      and Klebsiella pneumoniae (ATCC 700603) using the macrodilution broth
      susceptibility test method. After incubation in tubes, the antibacterial activity
      of curcumin was detected by a lack of turbidity, which indicated the inhibition
      of bacterial growth. The concentration in the tube with the highest dilution
      showing no turbidity was defined as the MIC. RESULTS: The curcumin MIC values
      were 175 ug/ml, 129 ug/ml, 219 ug/ml, 217 ug/ml, 163 ug/ml, 293 ug/ml and 216
      ug/ml against P. aeruginosa, B. subtilis, MSSA, MRSA, E. coli, E. faecalis and K.
      Pneumonia, respectively. CONCLUSION: This study revealed antibacterial effects of
      curcumin against standard bacterial strains in high concentrations. Animal
      experiments have demonstrated that curcumin applied at high doses has strong
      antibacterial activity. There is a need for further in vivo studies to shed light
      on antibacterial effects of curcumin with high concentrations.

PMID- 24097362
TI  - Intervention of ginger or propolis ameliorates methotrexate-induced ileum
      toxicity.
AB  - The long-term clinical use of methotrexate (MTX) is restricted due to its severe
      intestinal toxicity. The protective effect of ginger or propolis on the toxicity
      induced by MTX is relatively less understood, so the possible protective effect
      of ginger or propolis, used separately, was investigated. A total of 60 male
      albino rats were divided into six groups as follows: (1) control group; (2)
      ginger group; (3) propolis group; (4) MTX group; (5) ginger + MTX group; and (6)
      propolis + MTX group. The present results show that MTX caused ileum injury,
      including shortening and fusion of the villi, inflammatory cell infiltration and
      goblet cell depletion. Administration of ginger or propolis ameliorated the MTX
      induced ileum injury as shown by histological, immunohistochemical and
      ultrastructural investigations and statistical analysis. This is revealed by
      intact villi, which shows marked increase in brown colouration of proliferating
      cell nuclear antigen positive nuclei in the crypts region, improvement in the
      number of goblet cells and brush border length of ileum. The current results
      conclude the efficacy and safety of ginger and propolis, which may be due to
      their antioxidant properties.

PMID- 24097363
TI  - Mobile phone radiation during pubertal development has no effect on testicular
      histology in rats.
AB  - Mobile phones are extensively used throughout the world. There is a growing
      concern about the possible public health hazards posed by electromagnetic
      radiation emitted from mobile phones. Potential health risk applies particularly
      to the most intensive mobile phone users-typically, young people. The aim of this
      study was to investigate the effects of mobile phone exposure to the testes, by
      assessing the histopathological and biochemical changes in the testicular germ
      cells of rats during pubertal development. A total of 12 male Sprague Dawley rats
      were used. The study group (n = 6) was exposed to a mobile phone for 1 h a day
      for 45 days, while the control group (n = 6) remained unexposed. The testes were
      processed with routine paraffin histology and sectioned. They were stained with
      hematoxylin-eosin, caspase 3, and Ki-67 and then photographed. No changes were
      observed between the groups (p > 0.05). The interstitial connective tissue and
      cells of the exposed group were of normal morphology. No abnormalities in the
      histological appearance of the seminiferous tubules, including the spermatogenic
      cycle stage, were observed. Our study demonstrated that mobile phones with a low
      specific absorption rate have no harmful effects on pubertal rat testicles.

PMID- 24097364
TI  - Effects of aflatoxin B1 on oxidative stress markers and apoptosis of spleens in
      broilers.
AB  - The purpose of the present study was to investigate the oxidative damage and
      apoptosis induced by aflatoxin B1 (AFB1) in spleen of broilers. A total of 200
      one-day-old avian male broilers were randomly divided into 4 equal groups of 50
      each and were fed for 21 days as follows: a control diet and three AFB1 diets
      containing 0.15, 0.3, and 0.6 mg AFB1/kg diet. Consumption of AFB1 diets induced
      oxidative stress in the spleen of chicken as evidenced by reduced glutathione
      peroxidase, glutathione reductase, and catalase activities, decreased glutathione
      contents, and increased malondialdehyde contents in explaining the pathogenesis.
      Flow cytometer method and terminal deoxynucleotidyl transferase-mediated
      deoxyuridine triphosphate nick end-labeling assay revealed that the apoptotic
      splenocytes were increased in AFB1 groups. The results suggest that AFB1 induced
      excessive apoptosis of splenic lymphocytes, which is correlated with increased
      oxidative stress. The present results may be helpful for explaining the
      pathogenesis of AFB1-induced immunosuppression.

PMID- 24097365
TI  - Investigation of cadmium pollution in the spruce saplings near the metal
      production factory.
AB  - Toxic metals such as lead and cadmium are among the pollutants that are created
      by the metal production factories and disseminated in the nature. In order to
      study the quantity of cadmium pollution in the environment of the metal
      production factories, 50 saplings of the spruce species at the peripheries of the
      metal production factories were examined and the samples of the leaves, roots,
      and stems of saplings planted around the factory and the soil of the environment
      of the factory were studied to investigate pollution with cadmium. They were
      compared to the soil and saplings of the spruce trees planted outside the factory
      as observer region. The results showed that the quantity of pollution in the
      leaves, stems, and roots of the trees planted inside the factory environment were
      estimated at 1.1, 1.5, and 2.5 mg/kg, respectively, and this indicated a
      significant difference with the observer region (p < 0.05). The quantity of
      cadmium in the soil of the peripheries of the metal production factory was
      estimated at 6.8 mg/kg in the depth of 0-10 cm beneath the level of the soil. The
      length of roots in the saplings planted around the factory of metal production
      stood at 11 and 14.5 cm in the observer region which had a significant difference
      with the observer region (p < 0.05). The quantity of soil resources and spruce
      species' pollution with cadmium in the region has been influenced by the
      production processes in the factory.

PMID- 24097366
TI  - Evaluation of teratogenic effects of crocin and safranal, active ingredients of
      saffron, in mice.
AB  - Saffron (Crocus sativus) is a widely used food additive for its color and taste.
      Crocin and safranal are two main components of this plant. Numerous studies are
      underway to introduce saffron and its active ingredients as pharmacological
      agents. Safety assessments of these compounds are important parts of this
      endeavor. In this study, the effects of crocin and safranal administrations
      during embryogenesis have been investigated in mice. A total of 75 BALB/c
      pregnant mice were divided into six experimental and control groups. Four
      experimental groups received intraperitoneal injection of crocin (200 mg/kg or
      600 mg/kg) daily or safranal (0.075 ml/kg or 0.225 ml/kg) on gestational days
      (GDs) 6 to 15. Control groups received normal saline or paraffin as solvents of
      crocin and safranal. Dams were dissected on GD18 and embryos were collected.
      Routine maternal and fetal parameters were recorded. Macroscopic observation of
      external malformations was also performed. Fetuses were then selected for double
      skeletal staining with alizarin red and alcian blue. All experimental groups
      caused significant decrease in length and weight of fetuses when compared with
      the control groups and revealed malformations such as minor skeletal
      malformations, mandible and calvaria malformations, and growth retardation. Minor
      skeletal malformations were the most commonly observed abnormality, which were
      statistically significant when compared with the control groups (p < 0.05). The
      severities of malformations were comparable in the crocin- and safranal-treated
      groups. This study suggests that crocin or safranal can induce embryonic
      malformations when administered in pregnant mice. Due to the wide use of saffron,
      further elaborate studies to understand the malformation mechanisms of these
      ingredients are recommended.

PMID- 24097367
TI  - Bioinoculants: A sustainable approach to maximize the yield of Ethiopian mustard
      (Brassica carinata L.) under low input of chemical fertilizers.
AB  - This study aimed to find out the effect of plant growth-promoting rhizobacteria
      (PGPR; Azospirillum brasilense and Azotobacter vinelandii) either alone or in
      combination with different doses of nitrogen and phosphate fertilizers on growth,
      seed yield, and oil quality of Brassica carinata (L.) cv. Peela Raya. PGPR were
      applied as seed inoculation at 10(6) cells/mL(-1) so that the number of bacterial
      cells per seed was 2.6 * 10(5) cells/seed. The chemical fertilizers, namely, urea
      and diammonium phosphate (DAP) were applied in different doses (full dose (urea
      160 kg ha(-1) + DAP 180 kg ha(-1)), half dose (urea 80 kg ha(-1) + DAP 90 kg ha(
      1)), and quarter dose (urea 40 kg ha(-1) + DAP 45 kg ha(-1)). The chemical
      fertilizers at full and half dose significantly increased the chlorophyll,
      carotenoids, and protein content of leaves and the seed yield (in kilogram per
      hectare) but had no effect on the oil content of seed. The erucic acid (C22:1)
      content present in the seed was increased. Azospirillum performed better than
      Azotobacter and its effect was at par with full dose of chemical fertilizers
      (CFF) for pigments and protein content of leaves when inoculated in the presence
      of half dose of chemical fertilizers (SPH). The seed yield and seed size were
      greater. Supplementing Azospirillum with SPH assisted Azospirillum to augment the
      growth and yield, reduced the erucic acid (C22:1) and glucosinolates contents,
      and increased the unsaturation in seed oil. It is inferred that A. brasilense
      could be applied as an efficient bioinoculant for enhancing the growth, seed
      yield, and oil quality of Ethiopian mustard at low fertilizer costs and
      sustainable ways.

PMID- 24097368
TI  - Impact of caffeic acid phenethyl ester treatment on vancomycin-induced pancreatic
      damage in rats.
AB  - This study investigates the preventive effect of caffeic acid phenethyl ester
      (CAPE) on pancreatic damage induced by vancomycin (VCM) in rats. Rats were
      equally divided into three groups: group I (control), group II (only VCM-treated
      group) and group III (VCM + CAPE-treated groups). VCM was intraperitoneally
      administered at a dose of 200 mg kg(-1)twice daily for 7 days. CAPE was
      administered orally at 10 uM mL(-1) kg(-1) dose once daily for 7 days. The first
      dose of CAPE administration was performed 24 h prior to VCM injection. Blood and
      pancreas tissue samples were removed and collected after the study. Serum
      alkaline phosphatase (ALP), amylase, gamma-glutamyl transferase (GGT) and lipase
      activities were determined. Pancreas tissue samples were evaluated with the light
      microscope. Group II significantly increased serum ALP, amylase, GGT and lipase
      activities when compared with the control group. Group III significantly
      decreased serum ALP, amylase, GGT and lipase activities when compared with group
      II. In histopathological examination, it has been observed that there was a
      significant pancreatic damage in group II. CAPE exerted prominent structural
      protection against VCM-induced pancreatic damage and this effect was
      statistically significant. CAPE caused a marked reduction in the extent of
      pancreatic damage. We have concluded that it may play an important role in the
      VCM-induced pancreatic damage and reduce the pancreatic damage both at the
      biochemical and histopathological aspects.

PMID- 24097369
TI  - Protective effects of caffeic acid phenethyl ester on ifosfamide-induced central
      neurotoxicity in rats.
AB  - BACKGROUND: The aim of this study was to establish the protective effect of
      caffeic acid phenethyl ester (CAPE) against the ifosfamide (IFOS)-induced central
      neurotoxicity in rats and to determine the changes in oxidant-antioxidant status
      of brain tissue. METHOD: A total of 35 Wistar rats (aged 7-12 days) were used in
      the experiments. The study comprised of five groups. Control untreated rats (n =
      7) belonged to group 1; group 2 was given intraperitoneal (IP) injection of CAPE
      alone (10 umol/kg; n = 7); group 3 was treated with single IP injection of IFOS
      (500 mg/kg; n = 7); group 4 was treated for 2 days with IP administration of CAPE
      (10 umol/kg) beginning from one day before single IP injection of IFOS (n = 7);
      and group 5 was treated with saline and 10% ethanol. At the 24th hour of IFOS
      treatment, brain tissues were removed for analysis. RESULTS: The brain catalase
      activity was lower in IFOS group than the other groups (p < 0.05). The levels of
      malondialdehyde (MDA) and protein carbonyl content in brain tissue were higher in
      IFOS group than the control, CAPE, ethanol, and IFOS + CAPE groups (p < 0.05).
      There was no significant difference between MDA and protein carbonyl content of
      control, CAPE, ethanol, and IFOS + CAPE groups. Immunohistochemistry showed
      marked activation of caspase 3 in the IFOS group at 24 h after treatment.
      CONCLUSION: This study revealed that pretreatment with CAPE might protect brain
      tissue against IFOS-induced central neurotoxicity. CAPE could be an effective
      course of therapy to enhance therapeutic efficacy and to lessen IFOS toxicity in
      clinical chemotherapy.

PMID- 24097370
TI  - Assessment of metal contents in spices and herbs from Saudi Arabia.
AB  - In the recent years, there has been a growing interest in monitoring heavy metal
      contamination of spices/herbs. Spices and herbs are sources of many bioactive
      compounds that can improve the tastes of food as well as influence digestion and
      metabolism processes. In the present study, the levels of some essential and
      toxic elements such as iron (Fe), zinc (Zn), copper (Cu), chromium (Cr),
      manganese (Mn), cobalt (Co), nickel (Ni), lead (Pb), and cadmium (Cd), present in
      common spices/herbs that were purchased from the local market in Saudi Arabia,
      were analyzed by atomic absorption spectroscopy after digestion with nitric
      acid/hydrogen peroxide mixture. Samples from the following spices/herbs were
      used: turmeric, cloves, black pepper, red pepper, cumin, legume, cinnamon,
      abazir, white pepper, ginger, and coriander. The concentration ranges for the
      studied elements were found as 48.8-231, 4.7-19.4, 2.5-10.5, below detection
      level (BDL)-1.0, 8.8-490, 1.0-2.6, and BDL-3.7 ug g(-1) for Fe, Zn, Cu, Cr, Mn,
      Ni, and Pb, respectively, while Cd and Co levels were below the detection limit.
      Consumers of these spices/herbs would not be exposed to any risk associated with
      the daily intake of 10 g of spices per day as far as metals Fe, Zn, Cu, Cr, Mn,
      Ni, and Pb are concerned.

PMID- 24097371
TI  - Unipolar signal modification as a guide for lesion creation during radiofrequency
      application in the left atrium: prospective study in humans in the setting of
      paroxysmal atrial fibrillation catheter ablation.
AB  - BACKGROUND: In patients treated for paroxysmal atrial fibrillation, the pulmonary
      vein (PV) reconnection rate is substantial and may be related to the lack of
      transmurality achievement while performing PV isolation (PVI). It has been
      experimentally demonstrated that positive unipolar atrial electrogram completion,
      when applying radiofrequency energy, was associated with transmural lesions. In
      this regard, we seek to determine whether the unipolar signal modification may be
      an appropriate end point for point-by-point radiofrequency application and find
      out whether it could improve the paroxysmal atrial fibrillation ablation results
      in humans. METHODS AND RESULTS: Fifty consecutive patients (61+/-8 years old, 41
      men) with paroxysmal atrial fibrillation underwent PVI using Carto and Lasso.
      Each radiofrequency application lasted until development of a completely positive
      unipolar electrogram. Fifty patients (63+/-9 years old, 40 men), who previously
      underwent PVI following the standard approach of our institution, corresponded to
      the control group. All PVs were isolated in all patients of both groups. However,
      the procedural and ablation times were significantly lower in the unipolar group
      compared with those of the control group, whereas the PV reconnection rate, after
      30 minutes of waiting time, was not significantly different. Overall, 21+/-4
      months after 1 PVI session, the sinus rhythm maintenance rate without
      antiarrhythmic drugs was significantly higher (P=0.027) in the unipolar group
      (88%) compared with that of the control group (70%). CONCLUSIONS: Unipolar signal
      modification is a useful end point for radiofrequency energy delivery in patients
      with paroxysmal atrial fibrillation who undergo PVI and leads to a substantial
      midterm sinus rhythm maintenance rate.

PMID- 24097372
TI  - Pulmonary vein isolation using a pace-capture-guided versus an adenosine-guided
      approach: effect on dormant conduction and long-term freedom from recurrent
      atrial fibrillation--a prospective study.
AB  - BACKGROUND: Atrial fibrillation recurrence after pulmonary vein (PV) isolation is
      associated with PV to left atrium reconduction. We prospectively studied the use
      of 2 procedural techniques designed to facilitate identification of residual gaps
      within the index ablation line. METHODS AND RESULTS: After wide circumferential
      PV isolation, 40 patients received additional ablation targeted at locations of
      left atrial capture during high-output pacing (pace-capture group), while 40
      patients underwent adenosine testing with targeted ablation at sites of dormant
      conduction (adenosine group). Patients were followed up at 3, 6, and 12 months.
      After PV isolation, high-output pace-capture was documented in 39 PVs (25%; 50%
      of patients) in the pace-capture group. Dormant conduction was unmasked in 34 PVs
      (22%; 53% of patients) in the adenosine group. A subset of 25 patients in the
      pace-capture group underwent adenosine testing without targeted ablation of
      dormant conduction. In these patients, only 10 out of 86 PVs (11.6%; 24% of
      patients) demonstrated dormant conduction after the elimination of local pace
      capture. At a follow-up of 329+/-124 days, the single procedure off
      antiarrhythmic drug freedom from recurrent atrial fibrillation was 67.5% in the
      adenosine group and 65.0% in the pace-capture group (P=0.814). Procedure duration
      and fluoroscopy time were significantly longer in the pace-capture group (P=0.002
      and P<0.001), whereas radiofrequency ablation time was comparable (P=0.192).
      CONCLUSIONS: The use of high-output pacing post-PV isolation results in a
      significant reduction in the incidence of dormant conduction with a comparable
      long-term freedom from recurrent atrial fibrillation (versus adenosine-guided
      ablation). The use of these approaches requires evaluation in a long-term
      prospective randomized study. [corrected].

PMID- 24097373
TI  - Clinical, electrocardiographic, echocardiographic characteristics and long-term
      follow-up of elite soccer players with J-point elevation.
AB  - BACKGROUND: J-point elevation is common in athletes; nevertheless, the influence
      of structural changes associated with the athlete's heart and its prognostic
      impact are still debated. Our aim was to investigate the prevalence of J-point
      elevation, the associated clinical, electrocardiographic, and echocardiographic
      characteristics and its impact on long-term outcome in elite soccer players.
      METHODS AND RESULTS: Clinical, electrocardiographic, and cardiopulmonary exercise
      test data from 332 male professional soccer players were retrospectively
      analyzed. For 235 (70.7%) athletes echocardiographic data were also available. J
      point elevation was defined as an elevation >=1 mm in >=2 contiguous leads. Long
      term follow-up data were obtained for all athletes, whereas univariate and
      multivariable analyses were performed to assess the associated characteristics.
      Overall, 118 (35.6%) athletes showed a J-point elevation >=1 mm. At multivariable
      analysis a significant direct association of interventricular septum thickness
      (odds ratio for 1 SD increase, 1.361; 95% confidence interval, 1.019-1.817;
      P=0.036) and Sokolow-Lyon index (odds ratio for 1 SD increase, 1.367; 95%
      confidence interval, 1.026-1.822; P=0.033) and an inverse association of baseline
      heart rate (odds ratio for 1 SD increase, 0.686; 95% confidence interval, 0.508
      0.927; P=0.011) with J-point elevation were observed. During a long-term follow
      up (median, 13.3 years; first and third quartiles, 10.1-17.0 years), a low
      mortality rate was observed, not related to cardiovascular causes. CONCLUSIONS:
      The correlation between J-point elevation and interventricular septum thickness
      suggests a possible mechanistic role of exercise-induced left ventricular
      hypertrophy as the basis for J-point elevation. After a long-term follow-up, no
      cardiac death was observed.

PMID- 24097374
TI  - MDMA enhances emotional empathy and prosocial behavior.
AB  - 3,4-Methylenedioxymethamphetamine (MDMA, 'ecstasy') releases serotonin and
      norepinephrine. MDMA is reported to produce empathogenic and prosocial feelings.
      It is unknown whether MDMA in fact alters empathic concern and prosocial
      behavior. We investigated the acute effects of MDMA using the Multifaceted
      Empathy Test (MET), dynamic Face Emotion Recognition Task (FERT) and Social Value
      Orientation (SVO) test. We also assessed effects of MDMA on plasma levels of
      hormones involved in social behavior using a placebo-controlled, double-blind,
      random-order, cross-over design in 32 healthy volunteers (16 women). MDMA
      enhanced explicit and implicit emotional empathy in the MET and increased
      prosocial behavior in the SVO test in men. MDMA did not alter cognitive empathy
      in the MET but impaired the identification of negative emotions, including
      fearful, angry and sad faces, in the FERT, particularly in women. MDMA increased
      plasma levels of cortisol and prolactin, which are markers of serotonergic and
      noradrenergic activity, and of oxytocin, which has been associated with prosocial
      behavior. In summary, MDMA sex-specifically altered the recognition of emotions,
      emotional empathy and prosociality. These effects likely enhance sociability when
      MDMA is used recreationally and may be useful when MDMA is administered in
      conjunction with psychotherapy in patients with social dysfunction or post
      traumatic stress disorder. 

PMID- 24097375
TI  - Rough primes and rough conversations: evidence for a modality-specific basis to
      mental metaphors.
AB  - How does our brain organize knowledge? Traditional theories assume that our
      knowledge is represented abstractly in an amodal conceptual network of formal
      logic symbols. The theory of embodied cognition challenges this view and argues
      that conceptual representations that constitute our knowledge are grounded in
      sensory and motor experiences. We tested this hypothesis by examining how the
      concept of social coordination is grounded metaphorically in the tactile
      sensation of roughness. Participants experienced rough or smooth touch before
      being asked to judge an ambiguous social interaction. Results revealed that rough
      touch made social interactions appear more difficult and adversarial, consistent
      with the rough metaphor. This impact of tactile cues on social impressions was
      accompanied by a network including primary and secondary somatosensory cortices,
      amygdala, hippocampus and inferior prefrontal cortex. Thus, the roughness of
      tactile stimulation affected metaphor-relevant (but not metaphor-irrelevant)
      behavioral and neural responses. Receiving touch from a rough object seems to
      trigger the application of associated ontological concepts (or scaffolds) even
      for unrelated people and situations (but not to unrelated or more general
      feelings). Since this priming was based on somatosensory brain areas, our results
      provide support for the theory that sensorimotor grounding is intrinsic to
      cognitive processes. 

PMID- 24097377
TI  - The importance of oocyte biology for the future of fertility preservation.

PMID- 24097376
TI  - Neural responses to facial expressions support the role of the amygdala in
      processing threat.
AB  - The amygdala is known to play an important role in the response to facial
      expressions that convey fear. However, it remains unclear whether the amygdala's
      response to fear reflects its role in the interpretation of danger and threat, or
      whether it is to some extent activated by all facial expressions of emotion.
      Previous attempts to address this issue using neuroimaging have been confounded
      by differences in the use of control stimuli across studies. Here, we address
      this issue using a block design functional magnetic resonance imaging paradigm,
      in which we compared the response to face images posing expressions of fear,
      anger, happiness, disgust and sadness with a range of control conditions. The
      responses in the amygdala to different facial expressions were compared with the
      responses to a non-face condition (buildings), to mildly happy faces and to
      neutral faces. Results showed that only fear and anger elicited significantly
      greater responses compared with the control conditions involving faces. Overall,
      these findings are consistent with the role of the amygdala in processing threat,
      rather than in the processing of all facial expressions of emotion, and
      demonstrate the critical importance of the choice of comparison condition to the
      pattern of results. 

PMID- 24097378
TI  - The control of oocyte survival by intrinsic and extrinsic factors.
AB  - CAPSULE: Mechanisms that control the survival of oocytes and, by extension, the
      duration of ovarian function have been identified. However, it is still not clear
      whether oocyte "quality" is related to survival, nor is the role of the granulosa
      cells of follicles in follicle survival entirely understood. Here, we consider
      oocyte-intrinsic and oocyte-extrinsic mechanisms of oocyte loss and argue that
      developing a better understanding of such physiological events is needed to
      protect fertility, fecundity, and ovarian function in women.The duration that
      ovaries function is, as is intuitive, controlled by the number of remaining
      oocytes within follicles. Once the number of follicles drops beneath a threshold
      number, ovarian function ceases. Thus, understanding mechanisms that control
      oocyte survival is paramount as we consider strategies to protect or prolong
      ovarian function in women. It is often assumed that physiological oocyte survival
      is entirely controlled by "oocyte- intrinsic" factors, such as poor genetic
      quality or accumulated damage to the oocyte itself. Oocytes that have poor
      genetic quality due to development or accumulated damage would then die sooner
      than those of higher "quality." Indeed, new data suggest that oocyte-intrinsic
      genetic quality as determined by the ability to repair double-stranded DNA breaks
      is a significant contributor to oocyte survival and the duration of ovarian
      function. However, the nature of the follicle, where the oocyte and surrounding
      granulosa cells exist in intimate contact and rely upon each other for survival
      signals and metabolic function, makes it unlikely that oocyte-intrinsic factors
      entirely control oocyte survival. We and others are assessing the role of
      adjacent somatic (granulosa) cells in follicle survival, determining the relative
      importance of "oocyte-extrinsic" factors.

PMID- 24097379
TI  - Effects of fertility preservation on oocyte genomic integrity.
AB  - An important adjunct to the field of fertility preservation is cryobiology. At
      present, the long-term storage of oocytes, embryos or ovarian tissues relies upon
      cryopreservation technologies that fall into roughly two different modalities:
      traditional slow freeze (SF) or rapid cooling, often invoking the process of
      vitrification. Unlike most cells in the body, female germ cells or oocytes
      present unique biophysical constraints as either isolated entities or within the
      context of ovarian follicles. Especially relevant is the fact that the oocyte
      nucleus, often referred to as the germinal vesicle, is highly hydrated and
      presents a voluminous non-chromatin occupied space that undergoes significant
      alterations in chromatin organization during its development. While the impact of
      cryopreservation on the integrity of the oocyte plasma membrane, organelles, and
      spindle cytoskeleton have been the focus of most studies to date, the short-term
      and long-term consequences of chilling and cryoprotectants on the chromosomal and
      genomic integrity has received much less attention. This chapter reviews the
      topic of genomic integrity at the level of the oocyte and provides guidelines for
      the design and implementation of strategies that will permit objective assessment
      of current and future protocols applied in the field of fertility preservation. 

PMID- 24097380
TI  - In vitro activation of dormant follicles for fertility preservation.
AB  - Recent advances in radiotherapy and chemotherapy have led to higher cure rates
      for female children and adolescents with cancer. However, these treatments
      adversely affect germ cell survival, and ovarian failure is thus a probable side
      effect of these anticancer therapies. Moreover, an increasing number of women are
      choosing to postpone childbearing until later in life, but their primordial
      follicle reserves degenerate with advancing age. Thus there is a pressing need
      for the development of fertility preservation methods for these individuals.
      Ovarian tissue cryopreservation prior to loss of the primordial follicle
      population either due to cancer treatments or normal aging is a promising option
      for safeguarding fertility. A complete in vitro maturation (IVM) system could
      help generate mature eggs for later use without the patient having to undergo the
      cumbersome process involved in current assisted reproduction methods to generate
      mature eggs. Cryopreserved ovarian cortical tissues have attracted the attention
      of reproductive biologists and clinicians because of the large number of safely
      frozen primordial follicles in them, and it is theoretically possible to use
      these follicles for in vitro activation (IVA) and subsequent IVM. Ovarian tissue
      collection is independent of patient age and social or personal conditions.
      Despite being widely accepted potential techniques for fertility preservation,
      IVA and IVM of human primordial follicles to obtain fertilizable eggs remains far
      from reality. This chapter highlights the current achievements and obstacles in
      obtaining growing follicles through activation of dormant follicles. 

PMID- 24097382
TI  - Vitrification of oocytes: from basic science to clinical application.
AB  - Vitrification is a physical process by which a liquid is transformed into a solid
      of amorphous glass form. It was only at the end of the nineteenth century (1898)
      that Gustav Heinrich Johann Apollon Tammann pointed out that a large number of
      substances can be obtained as glasses and suggested that this property might be
      universal (Tammann, Zeitschrift for Physikalische Chemie; 25: 441-479, 1898).
      Basically, vitrification is the supercooling of a liquid to a temperature at
      which the viscosity is so high that it can be defined as being at a solid state.
      The understanding of the vitrification process has been deepened over the years
      and has been applied for cryopreservation and currently is the method of choice
      for preserving oocytes and embryos. 

PMID- 24097383
TI  - Memoir of fertility preservation.
AB  - Fertility preservation has been practiced for at least 50 years using semen
      banking, pelvic surgery, and radiation shields, but in the past 20 years it has
      emerged as a rapidly growing subspecialty of reproductive medicine. A dramatic
      rise in survivorship of young cancer patients and the widespread postponement of
      family building to the later years of the female reproductive lifespan have been
      major driving forces. Throughout the history of fertility preservation, low
      temperature banking has played a pivotal role, first for gametes and later for
      embryos and immature germ cells, while ovarian transplantation recently began to
      contribute and spermatogonial stem cell transfer holds future promise for men and
      prepubertal boys. But there are significant risks with some diseases from
      reimplanting residual disease, which hopefully can be eliminated by new methods
      for purging the tissue and germ cell culture. Since all technologies are interim,
      cryopreservation as a mainstay in this field will likely be swept aside
      eventually by a stream of progress aimed at managing fertility preservation in
      vivo. 

PMID- 24097381
TI  - Primate follicular development and oocyte maturation in vitro.
AB  - The factors and processes involved in primate follicular development are complex
      and not fully understood. An encapsulated three-dimensional (3D) follicle culture
      system could be a valuable in vitro model to study the dynamics and regulation of
      folliculogenesis in intact individual follicles in primates. Besides the research
      relevance, in vitro follicle maturation (IFM) is emerging as a promising approach
      to offer options for fertility preservation in female patients with cancer. This
      review summarizes the current published data on in vitro follicular development
      from the preantral to small antral stage in nonhuman primates, including follicle
      survival and growth, endocrine (ovarian steroid hormone) and paracrine/autocrine
      (local factor) function, as well as oocyte maturation and fertilization. Future
      directions include major challenges and strategies to further improve follicular
      growth and differentiation with oocytes competent for in vitro fertilization and
      subsequent embryonic development, as well as opportunities to investigate primate
      folliculogenesis by utilizing this 3D culture system. The information may be
      valuable in identifying optimal conditions for human follicle culture, with the
      ultimate goal of translating the experimental results and products to patients,
      thereby facilitating diagnostic and therapeutic approaches for female fertility. 

PMID- 24097384
TI  - Fragmentations of [M-H]- anions of peptides containing Ser sulfate. A joint
      experimental and theoretical study.
AB  - RATIONALE: To determine the negative-ion cleavages from [M-H](-) ions of Ser
      sulfate-containing peptides using experiment and theory in concert. METHODS:
      Fragmentations were explored using a Waters QTOF2 mass spectrometer in negative
      ion electrospray mode, together with calculations at the CAM-B3LYP/6-311++g(d,p)
      level of theory. Peptides used in this study were: GS(SO3H)(OH) 1 GS(SO3H)(OCH3)
      1a GAVS(SO3H)(OH) 2 GAVS(SO3H)(OCH3) 2a GLS(SO3H)(GVA(OH) 3 GLS(SO3H)GDA(OH) 4
      GLS(SO3H)GS(SO3H)A(OH) 5. RESULTS: Previously, it has been shown that a peptide
      containing a Tyr sulfate group shows [(M-H)(-) -SO3] as the base peak. Only a
      small peak was observed corresponding to HOSO3(-) (formed following rearrangement
      of the sulfate). A Ser sulfate-containing peptide, in contrast, shows pronounced
      peaks due to cleavage product anions [(M-H)(-)-SO3] and HOSO3(-). Theoretical
      calculations at the CAM-B3LYP/6-311++g(d,p) level of theory suggest that
      rearrangement of a Ser sulfate to give C-terminal CO2SO3H is energetically
      unfavourable in comparison with fragmentation of the intact Ser sulfate to yield
      [(M-H)(-)-SO3] and HOSO3(-). [(M-H)(-)-H2SO4] anions are not observed in the
      spectra of peptides containing Ser sulfate, presumably because HOSO3(-) is a
      relatively weak gas-phase base (DeltaGacid = 1265 kJ mol(-1)). CONCLUSIONS:
      Experimental and theoretical data suggest that [(M-H)(-)-SO3] and HOSO3(-)
      product anions (from a peptide with a C-terminal Ser sulfate) are formed from the
      serine sulfate anion accompanied by specific proton transfer. CID MS/MS/MS data
      for an [(M-H)(-)-SO3] ion of an underivatised sulfate-containing peptide will
      normally allow the determination of the amino acid sequence of that peptide. The
      one case we have studied where that is not the case is GLS(SO3H)GDA(OH), where
      the peptide contains Ser sulfate and Asp, where the diagnostic Asp cleavages are
      competitive with the Ser sulfate cleavages.

PMID- 24097385
TI  - An integrated exact mass spectrometric strategy for comprehensive and rapid
      characterization of phenolic compounds in licorice.
AB  - RATIONALE: Licorice (Gancao) is derived from the dried roots and rhizomes of
      Glycyrrhiza species (Leguminosae) and appears as a component herb in about 60% of
      traditional Chinese medicine (TCM) prescriptions. Modern pharmacological studies
      have shown that flavonoids are one class of the major components responsible for
      the bioactivities of licorice. Ultra-performance liquid chromatography coupled
      with quadrupole time-of-flight mass spectrometry (UPLC/QTOF MS) has proven to be
      a powerful tool for rapid profiling and identification of natural products in
      complex herbal medicines. METHODS: A UPLC/QTOF MS method was established for the
      first time for profiling and structural characterization of the phenolic
      compounds (most of them flavonoids) in licorice. The combined use of data
      independent acquisition (MS(E) ) and data-dependent acquisition (DDA) was
      illustrated. RESULTS: Fifteen flavonoid reference compounds were used to explore
      the fragmentation pathways. Compound identification was based upon the exact
      mass, general fragmentation behaviors, retention times, UV absorption, and the
      related botanical biogenesis. As a result, a total of 51 compounds were
      characterized, three of which were reported for the first time. CONCLUSIONS: The
      LC/MS analysis for each injection took less than 9 min. The developed method is
      fast, accurate and reliable due to its high resolution and high efficiency
      characteristics as a result of combining both UPLC separation and QTOF exact mass
      measurement.

PMID- 24097386
TI  - Electrostatic-spray ionization mass spectrometry sniffing for perfume
      fingerprinting.
AB  - RATIONALE: The perfume market is growing significantly, and it is easy to find
      imitative fragrances of probably all types of perfume. Such imitative fragrances
      are usually of lower quality than the authentic ones, creating a possible threat
      for perfume companies. Therefore, it is important to develop efficient chemical
      analysis techniques to screen rapidly perfume samples. METHODS: Electrostatic
      spray ionization (ESTASI) was used to analyze directly samples sprayed or
      deposited on different types of paper. A linear ion trap mass spectrometer was
      used to detect the ions produced by ESTASI with a modified extended transfer
      capillary for 'sniffing' ions from the paper. RESULTS: Several commercial
      perfumes and a model perfume were analyzed by ESTASI-sniffing. The results
      obtained by paper ESTASI-MS of commercial fragrances were compared with those
      obtained from ESI-MS. In addition, a commercial fragrance was first nebulized on
      the hand and then soaked up by blotting paper, which was afterwards placed on an
      insulating plate for ESTASI-MS analysis. Analysis of peptides and proteins was
      also performed to show that the paper ESTASI-MS could be used for samples with
      very different molecular masses. CONCLUSIONS: Paper ESTASI-MS yields a rapid
      fingerprinting characterization of perfume fragrances, avoiding time-consuming
      sample-preparation steps, and thereby performing a rapid screening in a few
      seconds.

PMID- 24097387
TI  - Ozonation degrades all detectable organic compound classes in oil sands process
      affected water; an application of high-performance liquid chromatography/obitrap
      mass spectrometry.
AB  - RATIONALE: Surface mining of bitumen in Northern Alberta, Canada, results in
      large volumes of toxic oil sands process-affected water (OSPW) that must be
      contained in tailings ponds. Ozonation has shown great promise as an OSPW
      treatment process, by decreasing its toxicity and increasing its
      biodegradability, but the effect of ozonation on the thousands of dissolved
      organic chemical groups has not yet been examined. METHODS: Reversed-phase liquid
      chromatography with ultrahigh-resolution linear ion trap-orbitrap mass
      spectrometry was applied to the characterization of treated (utilized ozone doses
      of 20 and 50 mg O3/L) and untreated OSPW. The analysis was performed in positive
      and negative electrospray ionization modes for each sample (ESI(+)/ESI(-)).
      RESULTS: Semi-quantitative analysis of ozonated and unozonated samples allowed
      degradation to be monitored for naphthenic acids (i.e. O2 species in ESI(-) mode)
      and >2000 other organic species belonging to various heteroatom-containing
      classes: Ox (where x = 1 to 6), NOx (where x = 1 to 4), SOx (where x = 1 to 4),
      NO2 S, N, and S. No chlorinated byproducts were detected in any treated sample,
      but at the low dose (20 mg O3/L) some compound classes increased in abundance
      (e.g. the O5 class), indicating that they were formed as byproducts at faster
      rates than they were degraded. Nevertheless, all organic compound classes
      subsequently diminished at the higher dose (50 mg O3/L). For several Ox and SOx
      classes, species observed in ESI(+) mode (e.g. O2(+) species) were often more
      recalcitrant to ozonation than the corresponding species detected in ESI(-) mode
      (e.g. O2(-) species; naphthenic acids). CONCLUSIONS: Ozonation appears to be a
      very suitable treatment option for OSPW, but the more recalcitrant groups of
      compounds may help to explain the residual toxicity of ozonated OSPW. Analysis of
      OSPW constituents in both ionization modes is warranted in all future OSPW fate
      studies.

PMID- 24097388
TI  - High-precision measurement of phenylalanine delta15N values for environmental
      samples: a new approach coupling high-pressure liquid chromatography purification
      and elemental analyzer isotope ratio mass spectrometry.
AB  - RATIONALE: Compound-specific isotope analysis of individual amino acids (CSI-AA)
      is a powerful new tool for tracing nitrogen (N) source and transformation in
      biogeochemical cycles. Specifically, the delta(15)N value of phenylalanine
      (delta(15)N(Phe)) represents an increasingly used proxy for source delta(15)N
      signatures, with particular promise for paleoceanographic applications. However,
      current derivatization/gas chromatography methods require expensive and
      relatively uncommon instrumentation, and have relatively low precision, making
      many potential applications impractical. METHODS: A new offline approach has been
      developed for high-precision delta(15)N measurements of amino acids
      (delta(15)N(AA)), optimized for delta(15)N(Phe) values. Amino acids (AAs) are
      first purified via high-pressure liquid chromatography (HPLC), using a mixed
      phase column and automated fraction collection. The delta(15)N values are
      determined via offline elemental analyzer-isotope ratio mass spectrometry (EA
      IRMS). RESULTS: The combined HPLC/EA-IRMS method separated most protein AAs with
      sufficient resolution to obtain accurate delta(15)N values, despite significant
      intra-peak isotopic fractionation. For delta(15)N(Phe) values, the precision was
      +/-0.160/00 for standards, 4* better than gas chromatography/combustion/isotope
      ratio mass spectrometry (GC/C/IRMS; +/-0.640/00). We also compared a
      delta(15)N(Phe) paleo-record from a deep-sea bamboo coral from Monterey Bay, CA,
      USA, using our method versus GC/C/IRMS. The two methods produced equivalent
      delta(15)N(Phe) values within error; however, the delta(15)N(Phe) values from
      HPLC/EA-IRMS had approximately twice the precision of GC/C/IRMS (average stdev of
      0.270/00 +/- 0.140/00 vs 0.600/00 +/- 0.200/00, respectively). CONCLUSIONS: These
      results demonstrate that offline HPLC represents a viable alternative to
      traditional GC/C/IMRS for delta(15)N(AA) measurement. HPLC/EA-IRMS is more
      precise and widely available, and therefore useful in applications requiring
      increased precision for data interpretation (e.g. delta(15)N paleoproxies).

PMID- 24097389
TI  - High-temperature mass spectrometric determinations of relative ionization cross
      sections of gaseous TiO, TiO2, VO, VO2, YO, HfO and GeO molecules.
AB  - RATIONALE: Accurate values of electron ionization cross-sections of high
      temperature vapor species are of importance in mass spectrometric investigations
      as well as in a variety of other fields. However, the present experimental
      techniques are subject to many inherent difficulties or are limited in
      applicability and so far have yielded relatively few reliable values. Theoretical
      calculations are not sufficiently accurate. So the need for experimental
      ionization cross-section data for these species is very important. METHODS:
      Measurements were performed by high-temperature Knudsen effusion mass
      spectrometry with a MS-1301 mass spectrometer. Vaporization was carried out using
      molybdenum effusion cells containing samples of pure Au, V2O3, Ti3O5, GeO2 and
      Y2O3-HfO2 systems. RESULTS: The VO, VO2, TiO, TiO2, YO, HfO and GeO vapor species
      were identified over the samples studied. The partial pressures of Au and the
      oxides were measured by a complete isothermal vaporization method. The relative
      ionization cross-sections sigma(Au)/sigma(i) were determined for the gaseous
      oxides studied. The results were compared with the literature data. CONCLUSIONS:
      The inapplicability of the 'additivity rule' is shown. This finding is in good
      agreement with a tendency to changing ionization cross-sections in the Periodic
      Table row of gaseous M, MO and MO2 species.

PMID- 24097390
TI  - Complementary mass spectrometric approaches and scanning electron microscopy to
      study the structural stability of polyurethane tunneled dialysis catheters after
      exposure to ethanol solutions.
AB  - RATIONALE: Ethanol lock is an emerging therapeutic option for preventing and/or
      controlling catheter-associated infection. A previous study of silicone catheters
      showed they underwent no polymer degradation when kept in 60% ethanol for 15 days
      at 37  degrees C. The stability of the more widely used polyurethane catheters
      was studied here in the same way. METHODS: A qualitative and quantitative study
      of the stability of Carbothane(r) catheters was performed following their
      immersion at 37  degrees C in different solvents (0.9% sodium chloride as control
      medium and 40%, 60%, 95% ethanol solutions) for different periods of time (from 5
      min to 15 days) using scanning electron microscopy and complementary mass
      spectrometry techniques. RESULTS: Electron ionization analysis of the 95% ethanol
      storage solutions revealed the release of about 45 products (8 of which were
      major) subdivided into two groups according to their fragmentation patterns.
      Combining all the mass spectrometric data made it possible to propose structures.
      Group I (major) originated from the polycarbonate diol component (soft segment)
      and group II (minor) from the dicyclohexylmethane-4,4'-diisocyanate component
      (rigid segment). Semi-quantitative gas chromatography/mass spectrometry (GC/MS)
      analysis showed that no significantly higher release was observed after immersion
      for 30 min at 37  degrees C in 40% ethanol (mean ratio = 0.677 +/- 0.068) than
      after immersion in reference 0.9% sodium chloride solution for 15 days (0.837 +/-
      0.127). CONCLUSIONS: A 30 min-40% (v/v) ethanol solution can be considered as
      safe for preventing the infectious complications of Carbothane(r) dialysis
      catheters, and a 30 min-60% (v/v) ethanol treatment can be occasionally used to
      eradicate established biofilm.

PMID- 24097391
TI  - Recombinant " IMS TAG" proteins--a new method for validating bottom-up matrix
      assisted laser desorption/ionisation ion mobility separation mass spectrometry
      imaging.
AB  - RATIONALE: Matrix-assisted laser desorption/ionisation mass spectrometry imaging
      (MALDI-MSI) provides a methodology to map the distribution of peptides generated
      by in situ tryptic digestion of biological tissue. It is challenging to correlate
      these peptides to the proteins from which they arise because of the many
      potentially overlapping and hence interfering peptide signals generated. METHODS:
      A recombinant protein has been synthesised that when cleaved with trypsin yields
      a range of peptide standards for use as identification and quantification markers
      for multiple proteins in one MALDI-IMS-MSI experiment. Mass spectrometry images
      of the distribution of proteins in fresh frozen and formalin-fixed paraffin
      embedded tissue samples following in situ tryptic digestion were generated by
      isolating signals on the basis of their m/z value and ion mobility drift time,
      which were correlated to matching peptides in the recombinant standard. RESULTS:
      Tryptic digestion of the IMS-TAG protein and MALDI-MS analysis yielded m/z values
      and ion mobility drift time for the signature peptides included in it. MALDI-IMS
      MSI images for the distribution of the proteins HSP90 and vimentin, in FFPE EMT6
      mouse tumours, and HSP90 and plectin in a fresh frozen mouse fibrosarcoma, were
      generated by extracting ion images at the corresponding m/z value and drift time
      from the tissue samples. CONCLUSIONS: The IMS-TAG approach provides a new means
      to confirm the identity of peptides generated by in situ digestion of biological
      tissue.

PMID- 24097392
TI  - Soil denitrification potential and its influence on N2O reduction and N2O
      isotopomer ratios.
AB  - RATIONALE: N2O isotopomer ratios may provide a useful tool for studying N2O
      source processes in soils and may also help estimating N2O reduction to N2.
      However, remaining uncertainties about different processes and their
      characteristic isotope effects still hamper its application. We conducted two
      laboratory incubation experiments (i) to compare the denitrification potential
      and N2O/(N2O+N2) product ratio of denitrification of various soil types from
      Northern Germany, and (ii) to investigate the effect of N2O reduction on the
      intramolecular (15)N distribution of emitted N2O. METHODS: Three contrasting
      soils (clay, loamy, and sandy soil) were amended with nitrate solution and
      incubated under N2 -free He atmosphere in a fully automated incubation system
      over 9 or 28 days in two experiments. N2O, N2, and CO2 release was quantified by
      online gas chromatography. In addition, the N2O isotopomer ratios were determined
      by isotope-ratio mass spectrometry (IRMS) and the net enrichment factors of the
      (15)N site preference (SP) of the N2O-to-N2 reduction step (eta(SP)) were
      estimated using a Rayleigh model. RESULTS: The total denitrification rate was
      highest in clay soil and lowest in sandy soil. Surprisingly, the N2O/(N2O+N2)
      product ratio in clay and loam soil was identical; however, it was significantly
      lower in sandy soil. The IRMS measurements revealed highest N2O SP values in clay
      soil and lowest SP values in sandy soil. The eta(SP) values of N2O reduction were
      between -8.2 and -6.10/00, and a significant relationship between delta(18)O and
      SP values was found. CONCLUSIONS: Both experiments showed that the N2O/(N2O+N2)
      product ratio of denitrification is not solely controlled by the available carbon
      content of the soil or by the denitrification rate. Differences in N2O SP values
      could not be explained by variations in N2O reduction between soils, but rather
      originate from other processes involved in denitrification. The linear delta(18)O
      vs SP relationship may be indicative for N2O reduction; however, it deviates
      significantly from the findings of previous studies.

PMID- 24097393
TI  - Development and optimization of a gas chromatography/mass spectrometry method for
      the analysis of thermochemolytic degradation products of phthiocerol
      dimycocerosate waxes found in Mycobacterium tuberculosis.
AB  - RATIONALE: The phthiocerol dimycocerosates (PDIMs) are certain stable and
      hydrophobic waxes found in the cell membrane of Mycobacterium tuberculosis,
      bacteria that cause an infectious disease of growing concern worldwide. Previous
      studies report the analysis of derivatives of the hydrolysed PDIMs from
      biological samples, following complex extraction and offline derivatization of
      PDIMs biomarkers, prior to their analysis by gas chromatography/mass spectrometry
      (GC/MS). METHODS: We developed and optimized a GC/MS method based on selected ion
      monitoring (SIM) to detect the derivatives produced via the thermally assisted
      hydrolysis and methylation (THM) of the PDIMs from the cell membrane of M.
      tuberculosis. The extraction of PDIMs from culture is simple, and their
      thermochemolysis is carried out automatically online, thus avoiding the time
      consuming derivatization steps of hydrolysis and esterification, usually
      performed offline. RESULTS: For standard PDIMs in petroleum ether, our optimized
      method gave an excellent linearity (R(2) = 0.99) at concentrations between 0.172
      and 27.5 ng/mL, a good precision (RSD = 11.42%), and a limit of detection (LOD)
      of 100 pg/mL. For the PDIMs extracted from dilutions of M. tuberculosis culture,
      the method gave good linearity (R(2) = 0.9685) and an estimated LOD of 400 CFU/mL
      (CFU = colony forming units) in sterile distilled water. CONCLUSIONS: A
      GC/MS(SIM) method is presented for the rapid and quantitative detection of M.
      tuberculosis, based on the online thermochemolysis of lipidic biomarkers
      extracted from the bacterial culture. The method has the potential to be applied
      in human and veterinary clinical laboratories for the rapid diagnosis of
      tuberculosis in infected biological samples.

PMID- 24097394
TI  - Characterisation of glycoproteins using a quadrupole time-of-flight mass
      spectrometer configured for electron transfer dissociation.
AB  - RATIONALE: Electron transfer dissociation (ETD) within ion trapping mass
      spectrometers has proven to be a useful tool for the characterisation of post
      translational modifications. In this study, we describe the implementation of ETD
      upon a modified quadrupole time-of-flight (Q-ToF) system and methods for the
      analysis of glycoproteins. METHODS: Liquid chromatography electrospray ionisation
      mass spectrometry (LC/ESI-MS) was performed using a hybrid quadrupole/ion
      mobility/oa-ToF mass spectrometer equipped with ETD functionality. 1,4
      Dicyanobenzene reagent anions necessary for the ETD reaction were generated from
      a glow discharge region located within the ESI source block. ETD reactions
      occurred in the stacked ring travelling wave ion guide (located after the
      quadrupole mass filter and prior to the oa-ToF mass analyser). LC/ETD was
      performed upon 'super-charged' tryptic glycopeptide ions produced from the
      recombinant monoclonal antibody trastuzumab. LC/ETD was also performed on ions
      from the smaller glycopeptides obtained from erythropoietin. RESULTS: ETD
      performed upon the quadruply 'super-charged' N-linked glycopeptide ions of
      trastuzumab and the triply charged O-linked glycopeptide ions of erythropoietin
      provided both glycosylation site assignments and full sequence information,
      respectively. Tandem mass (MS/MS) spectra employing collision-induced
      dissociation (CID) were dominated by oxonium product ions hampering full peptide
      sequence characterisation. CONCLUSIONS: LC/ETD on the Q-ToF system proved
      effective at characterising a number of different N-linked glyco-forms of the
      tryptic peptide, EEQYNSTYR, from trastuzumab as well as glyco-forms from the O
      linked tryptic peptide, EASIPPDAASAAPLR, from erythropoietin. The data
      demonstrates that the glycopeptide site heterogeneity of trastuzumab and
      erythropoietin can be accurately characterised. In addition, the post-column
      mixing of the super-charging reagent, m-NBA, is an effective method to increase
      the precursor ion charge state and to improve ETD reaction efficiency.

PMID- 24097395
TI  - On-line triple oxygen isotope analysis of nitrous oxide using decomposition by
      microwave discharge.
AB  - RATIONALE: The oxygen isotope anomaly, Delta(17)O, of N2O and nitrate is useful
      to elucidate nitrogen oxide dynamics. The previously developed method for
      Delta(17)O measurement presents difficulty in maintaining optimal conditions of
      the gold tube for thermal decomposition of N2O to O2 and the Delta(17)O value is
      also sample size dependent. METHODS: Trace amounts (5-40 nmol) of N2O were
      decomposed quantitatively to O2 in a quartz tube by microwave discharge. The O2
      was purified using gas chromatography. Triple oxygen isotopes were measured using
      isotope ratio mass spectrometry. Each step was connected online and was applied
      to the analysis of nitrate in precipitation samples collected in Yokohama, Japan.
      RESULTS: Precision (1sigma) of Delta(17)O analysis was better than 0.260/00 when
      more than 20 nmol of N2O with a small Delta(17)O value (approx. 10/00) was
      measured. It was better than 0.760/00 when more than 60 nmol of nitrate was
      converted into N2O using the denitrifier method and then measured on the
      developed system. The obtained Delta(17)O values in precipitation samples (14.5
      26.40/00) agreed with findings from previous studies. CONCLUSIONS: A novel on
      line analytical method was developed to measure the triple oxygen isotopes of N2O
      using microwave discharge to decompose N2O. This easy-to-use method is free from
      conditioning of reaction devices, and is applicable to molecules other than N2O
      such as NO and NO2.

PMID- 24097396
TI  - Can ion mobility mass spectrometry and density functional theory help elucidate
      protonation sites in 'small' molecules?
AB  - RATIONALE: Ion mobility spectrometry-mass spectrometry (IMS-MS) offers an
      opportunity to combine measurements and/or calculations of the collision cross
      sections and subsequent mass spectra with computational modelling in order to
      derive the three-dimensional structure of ions. IMS-MS has previously been
      reported to separate two components for the compound norfloxacin, explained by
      protonation on two different sites, enabling the separation of protonated isomers
      (protomers) using ion mobility with distinguishable tandem mass spectrometric
      (MS/MS) data. This study reveals further insights into the specific example of
      norfloxacin and wider implications for ion mobility mass spectrometry. METHODS:
      Using a quadrupole ion mobility time-of-flight mass spectrometer, the IMS and
      MS/MS spectra of norfloxacin were recorded and compared with theoretical
      calculations using molecular modelling (density functional theory), and
      subsequent collision cross-section calculations using projection approximation.
      RESULTS: A third significant component in the ion mobilogram of norfloxacin was
      observed under similar experimental conditions to those previously reported. The
      presence of the new component is convoluted by co-elution with another previously
      observed component. CONCLUSIONS: This case demonstrates the potential of combined
      IMS-MS/MS with molecular modelling information for increased understanding of
      'small-molecule' fragmentation pathways.

PMID- 24097397
TI  - Analysis of oxygen-17 excess of nitrate and sulfate at sub-micromole levels using
      the pyrolysis method.
AB  - RATIONALE: The oxygen-17 excess (Delta(17)O) of nitrate and sulfate contains
      valuable information regarding their atmospheric formation pathways. However, the
      current pyrolysis method to measure Delta(17)O requires large sample amounts (>4
      umol for nitrate and >1 umol for sulfate). We present a new approach employing a
      Gas Bench interface which cryofocuses O2 produced from sample pyrolysis, enabling
      the analysis of sub-micromole size samples. METHODS: Silver nitrate or sulfate at
      sub-micromole levels in a sample container was thermally decomposed to O2 and
      byproducts in a modified Temperature Conversion/Elemental Analyzer (TC/EA).
      Byproducts (mainly NO2 for silver nitrate and SO2 for silver sulfate) were
      removed in a liquid nitrogen trap and the sample O2 was carried by ultra-pure
      helium (He) gas to a Gas Bench II interface where it was cryofocused prior to
      entering an isotope ratio mass spectrometer. RESULTS: Analysis of the
      international nitrate reference material USGS35 (Delta(17)O = 21.60/00) within
      the size range of 300-1000 nmol O2 gave a mean Delta(17)O value of (21.6 +/-
      0.69) 0/00 (mean +/-1sigma). Three inter-laboratory calibrated sulfate reference
      materials, Sulf-alpha, Sulf-beta and Sulf-epsilon, each within the size range of
      180-1000 nmol O2, were analyzed and shown to possess mean Delta(17)O values of
      (0.9 +/- 0.10)0/00, (2.1 +/- 0.25)0/00 and (7.0 +/- 0.63)0/00, respectively.
      CONCLUSIONS: The analyses of nitrate and sulfate reference materials at sub
      micromole levels gave Delta(17)O values consistent with their accepted values.
      This new approach of employing the Gas Bench to cryofocus O2 after the pyrolysis
      of AgNO3 and Ag2SO4 particularly benefits the effort of measuring Delta(17)O in
      sample types with a low abundance of nitrate and sulfate such as ice cores.

PMID- 24097398
TI  - The quantitative surface analysis of an antioxidant additive in a lubricant oil
      matrix by desorption electrospray ionization mass spectrometry.
AB  - RATIONALE: Chemical additives are incorporated into commercial lubricant oils to
      modify the physical and chemical properties of the lubricant. The quantitative
      analysis of additives in oil-based lubricants deposited on a surface without
      extraction of the sample from the surface presents a challenge. The potential of
      desorption electrospray ionization mass spectrometry (DESI-MS) for the
      quantitative surface analysis of an oil additive in a complex oil lubricant
      matrix without sample extraction has been evaluated. METHODS: The quantitative
      surface analysis of the antioxidant additive octyl (4-hydroxy-3,5-di-tert
      butylphenyl)propionate in an oil lubricant matrix was carried out by DESI-MS in
      the presence of 2-(pentyloxy)ethyl 3-(3,5-di-tert-butyl-4
      hydroxyphenyl)propionate as an internal standard. A quadrupole/time-of-flight
      mass spectrometer fitted with an in-house modified ion source enabling non
      proximal DESI-MS was used for the analyses. RESULTS: An eight-point calibration
      curve ranging from 1 to 80 ug/spot of octyl (4-hydroxy-3,5-di-tert
      butylphenyl)propionate in an oil lubricant matrix and in the presence of the
      internal standard was used to determine the quantitative response of the DESI-MS
      method. The sensitivity and repeatability of the technique were assessed by
      conducting replicate analyses at each concentration. The limit of detection was
      determined to be 11 ng/mm(2) additive on spot with relative standard deviations
      in the range 3-14%. CONCLUSIONS: The application of DESI-MS to the direct,
      quantitative surface analysis of a commercial lubricant additive in a native oil
      lubricant matrix is demonstrated.

PMID- 24097399
TI  - Constructing a mass measurement error surface to improve automatic annotations in
      liquid chromatography/mass spectrometry based metabolomics.
AB  - RATIONALE: Estimation of mass measurement accuracy is an elementary step in the
      application of mass spectroscopy (MS) data towards metabolite annotations and has
      been addressed several times in the past. However, the reproducibility of mass
      measurements over a diverse set of analytes and in variable operating conditions,
      which are common in high-throughput metabolomics studies, has, to the best of our
      knowledge, not been addressed so far. METHODS: A method to automatically extract
      mass measurement errors from a large data set of measurements made on a
      quadrupole time-of-flight (QTOF) MS instrument has been developed. The size of
      the data processed in this study has enabled us to use a statistical data driven
      approach to build a model which reliably predicts the confidence interval of the
      absolute mass measurement error based on individual ion peak conditions in a
      fast, high-throughput manner. RESULTS: We show that our model predictions are
      reproducible in external datasets generated in similar, but not identical
      conditions, and have demonstrated the advantage of our approach over the common
      practice of fixed mass measurement error limits. CONCLUSIONS: Outlined is an
      approach which can promote a more rational use of MS technology by automatically
      evaluating the absolute mass measurement error based on the individual peak
      conditions. The immediate application of our method is integration in high
      throughput peak annotation pipelines for database searches.

PMID- 24097400
TI  - Atmospheric pressure chemical ionization Fourier transform ion cyclotron
      resonance mass spectrometry for complex thiophenic mixture analysis.
AB  - RATIONALE: Polycyclic aromatic sulfur heterocycles (PASHs) are detrimental
      species for refining processes in petroleum industry. Current mass spectrometric
      methods that determine their composition are often preceded by derivatization and
      dopant addition approaches. Different ionization methods have different impact on
      the molecular assignment of complex PASHs. The analysis of such species under
      atmospheric pressure chemical ionization (APCI) is still considered limited due
      to uncontrolled ion generation with low- and high-mass PASHs. METHODS: The
      ionization behavior of a model mixture of five selected PASH standards was
      investigated using an APCI source with nitrogen as the reagent gas. A complex
      thiophenic fraction was separated from a vacuum gas oil (VGO) and injected using
      the same method. The samples were analyzed using Fourier transform ion cyclotron
      resonance mass spectrometry (FTICR MS). RESULTS: PASH model analytes were
      successfully ionized and mainly [M + H](+) ions were produced. The same
      ionization pattern was observed for the real thiophenic sample. It was found that
      S1 class species were the major sulfur-containing species found in the VGO
      sample. These species indicated the presence of alkylated benzothiophenic (BT),
      dibenzothiophenic (DBT) and benzonaphthothiophenic (BNT) series that were
      detected by APCI-FTICR MS. CONCLUSIONS: This study provides an established APCI
      FTICR MS method for the analysis of complex PASHs. PASHs were detected without
      using any derivatization and without fragmentation. The method can be used for
      the analysis of S-containing crude oil samples.

PMID- 24097401
TI  - Comprehensive analysis of neurotransmitters from regenerating planarian extract
      using an ultrahigh-performance liquid chromatography/mass spectrometry/selected
      reaction monitoring method.
AB  - RATIONALE: Absolute quantification of neurotransmitters (NTs) from biological
      systems is imperative to track how changes in concentration of active
      neurochemicals may affect biological behavior. A sensitive method for the
      absolute quantification of multiple NTs in a single method is highly needed.
      METHODS: A stable-isotope dilution ultrahigh-performance liquid
      chromatography/mass spectrometry/selected reaction monitoring (UHPLC/MS/SRM)
      assay has been developed for a sensitive and quantitative assessment of NTs in
      planaria. We used this method for the simultaneous quantification of 16 NTs. All
      analytes showed a linear relationship between concentrations (0.78-50 ng/mL),
      regression coefficients higher than 0.97, accuracy (91-109%) and low coefficients
      of variation (CVs). The inter-day CVs for the lowest quality controls (1.56
      ng/mL) were in the range between 2-11%. RESULTS: The levels of most of the NTs
      were similar in both sexual and asexual planarians except for glutamic acid,
      which was about two-fold higher in asexual compared to sexual planarians. We
      identified high levels of serotonin and failed to detect tryptamine suggesting
      that the pathway essential for the conversion of tryptophan into tryptamine is
      absent in planarians. Interestingly, we also found high levels of dopamine and L
      DOPA in regenerating planarians suggesting their possible role in regeneration.
      CONCLUSIONS: For the first time, we developed novel methodology based on
      UHPLC/MS/SRM and quantified 16 NTs with high sensitivity and specificity from
      sexual and asexual strains of planarian Schmidtea mediterranea. This method will
      also have great application in quantifying various NTs with great precision in
      different model systems.

PMID- 24097403
TI  - Structural analysis of 2-arylidene-1-indanone derivatives by electrospray
      ionization tandem mass spectrometry.
AB  - RATIONALE: 2-arylidene-4-methoxy (or hydroxy)-7-methyl-1-indanone derivatives
      inspired from donepezil, the current drug used for the treatment of Alzheimer's
      disease as inhibitor of acetylcholinesterase (AChE), were studied for the first
      time by electrospray ionization mass spectrometry (ESI-MS) and tandem mass
      spectrometry (MS/MS). Structurally, these arylidene-indanone compounds are
      considered as cyclic analogues of chalcones. METHODS: ESI-MS and tandem mass
      spectra were acquired using a Q-TOF 2 instrument. Fragmentation patterns were
      analyzed by CID-MS(2-3) spectra acquired in a Q-TOF and in LXQ linear ion trap
      mass spectrometers using standard isolation and excitation procedures. RESULTS:
      All the 2-arylidene indanones have shown a common fragmentation pathway leading
      to a (2(1), 1')A(+) product ion at m/z 187 and the retro-aldol product ion [(2,
      2(1))B(+)] that allow to establish the substitution in the B ring. The effect of
      electron-donating and -withdrawing substituents on these fragmentation pathways
      was noticed. The presence of the OCH3, OH, NO2 and Br substituents gave typical
      fragmentation processes that allowed their unequivocal fingerprinting. The
      combined loss of the ortho substituent in the B-ring plus hydrogen (H, OCH3, Br
      and F) is proposed to form a stable cyclic ring product. CONCLUSIONS: Arylidene
      indanones with different substituents on the B ring are associated with a
      specific fragmentation pattern. In addition, differentiation between isomers with
      substituents in B ring at ortho and para positions were achieved using ESI-MS/MS.
      These fragmentation pathways can be used to further identify and determine the
      fate of these molecules in all stages of drug discovery.

PMID- 24097402
TI  - A novel Cookson-type reagent for enhancing sensitivity and specificity in
      assessment of infant vitamin D status using liquid chromatography/tandem mass
      spectrometry.
AB  - RATIONALE: 25-Hydroxyvitamin D3 [25(OH)D3] is the best-established indicator of
      vitamin D status. 4-Phenyl-1,2,4-triazoline-3,5-dione (PTAD), a representative
      Cookson-type reagent, has often been employed for enhancing the sensitivity in
      the trace determination of 25(OH)D3 in a neonatal dried blood spot (DBS), which
      contains only 2.65 MUL of whole blood, using liquid chromatography/electrospray
      ionization tandem mass spectrometry (LC/ESI-MS/MS). The objective of this study
      was the development of a novel Cookson-type reagent surpassing PTAD in terms of
      sensitivity and specificity in the LC/ESI-MS/MS assay of 25(OH)D3. METHODS: A
      novel Cookson-type reagent, 4-(4'-dimethylaminophenyl)-1,2,4-triazoline-3,5-dione
      (DAPTAD), was synthesized from 4-dimethylaminobenzoyl chloride. The DAPTAD
      derivative of 25(OH)D3 was prepared and its LC/ESI-MS/MS behavior was examined.
      The applicability of the DAPTAD-derivatization in the determination of 25(OH)D3
      in neonatal DBSs was also examined. RESULTS: The derivatization was completed at
      room temperature within 1 h. The DAPTAD-derivative of 25(OH)D3 provided a
      characteristic product ion derived from the cleavage of the vitamin D skeleton
      during MS/MS. The limit of detection of the DAPTAD-derivative during selected
      reaction monitoring was 0.25 fmol on the column, which was 30 and 2 times lower
      than those of the intact 25(OH)D3 and the PTAD-derivative, respectively. The
      DAPTAD-derivatization followed by LC/ESI-MS/MS enabled the detection of a trace
      amount (in the low-ng/mL range) of 25(OH)D3 in DBSs with a simple pretreatment
      (only methanol extraction) and short chromatographic run time (10 min). The
      DAPTAD-derivatization was also useful for the separation of 25(OH)D3 from a
      potent interfering metabolite, 3-epi-25-hydroxyvitamin D3 [3-epi-25(OH)D3]. On
      the contrary, the assay using the PTAD-derivatization might lead to
      overestimation of the true 25(OH)D3 levels due to the co-elution of 25(OH)D3 and
      3-epi-25(OH)D3. CONCLUSIONS: We developed DAPTAD for enhancing the sensitivity
      and specificity of the LC/ESI-MS/MS assay of 25(OH)D3. Our new method using
      DAPTAD can reduce the overestimation of the 25(OH)D3 levels, and will prove
      helpful in the diagnosis of vitamin D deficiency in infants.

PMID- 24097404
TI  - A membrane inlet mass spectrometry system for noble gases at natural abundances
      in gas and water samples.
AB  - RATIONALE: Noble gases dissolved in groundwater can reveal paleotemperatures,
      recharge conditions, and precise travel times. The collection and analysis of
      noble gas samples are cumbersome, involving noble gas purification, cryogenic
      separation and static mass spectrometry. A quicker and more efficient sample
      analysis method is required for introduced tracer studies and laboratory
      experiments. METHODS: A Noble Gas Membrane Inlet Mass Spectrometry (NG-MIMS)
      system was developed to measure noble gases at natural abundances in gas and
      water samples. The NG-MIMS system consists of a membrane inlet, a dry-ice water
      trap, a carbon-dioxide trap, two getters, a gate valve, a turbomolecular pump and
      a quadrupole mass spectrometer equipped with an electron multiplier. Noble gases
      isotopes (4)He, (22)Ne, (38)Ar, (84)Kr and (132)Xe are measured every 10 s.
      RESULTS: The NG-MIMS system can reproduce measurements made on a traditional
      noble gas mass spectrometer system with precisions of 2%, 8%, 1%, 1% and 3% for
      He, Ne, Ar, Kr and Xe, respectively. Noble gas concentrations measured in an
      artificial recharge pond were used to monitor an introduced xenon tracer and to
      reconstruct temperature variations to within 2  degrees C. Additional experiments
      demonstrated the capability to measure noble gases in gas and in water samples,
      in real time. CONCLUSIONS: The NG-MIMS system is capable of providing analyses
      sufficiently accurate and precise for introduced noble gas tracers at managed
      aquifer recharge facilities, groundwater fingerprinting based on excess air and
      noble gas recharge temperature, and field and laboratory studies investigating
      ebullition and diffusive exchange.

PMID- 24097405
TI  - Characterization of metabolites of GLS4 in humans using ultrahigh-performance
      liquid chromatography/quadrupole time-of-flight mass spectrometry.
AB  - RATIONALE: GLS4 is a heteroaryldihydropyrimidine compound that inhibits hepatitis
      B virus (HBV) replication by drug-induced depletion of nucleocapsids. It is
      currently undergoing clinical trials in China to treat HBV infection. The aim of
      this study was to identify the metabolites of GLS4 in humans. METHODS: A rapid
      and sensitive method based on ultrahigh-performance liquid
      chromatography/quadrupole time-of-flight tandem mass spectrometry was used to
      identify GLS4 metabolites in human plasma, urine, and feces after an oral dose of
      120 mg GLS4. RESULTS: A total of 27 metabolites were detected and identified by
      comparing the accurate molecular masses, retention times and spectral patterns of
      the analytes with those of the parent drug. Nine metabolites were confirmed by
      comparison with reference substances. All of the metabolites had a bromine atom
      and displayed the isotope ion of [M + H](+)/[M + H + 2](+) at a ratio of 1:1.
      Fragmentation of the dihydropyrimidine structure was characterized by the loss of
      the m-bromofluorobenzene group to generate an ion at m/z 220.0175. The morpholine
      ring was characterized by an ion at m/z 100.0757. CONCLUSIONS: The metabolites of
      GLS4 in humans were identified by the diagnostic ions of dihydropyrimidine and
      morpholine rings. GLS4 underwent extensive dealkylation, hydrolysis,
      dehydrogenation, oxidation, and glucuronidation reactions in humans.

PMID- 24097406
TI  - Development of a liquid chromatography/tandem mass spectrometry method to
      investigate the presence of biomarkers of DNA damage in urine related to red meat
      consumption and risk of colorectal cancer.
AB  - RATIONALE: The consumption of red meat is known to enhance the endogenous
      formation of N-nitroso compounds (NOCs), which are potent carcinogens. DNA damage
      related to NOCs, and hence red meat, has been detected in colorectal cells and in
      blood. We proposed to extend previous studies to a non-invasive approach for the
      detection of O(6)-carboxymethylguanine (O(6)CMG) and O(6)-carboxymethyl-2'
      deoxyguanosine (O(6)CMdG) in urine in relation to red meat intake using liquid
      chromatography/tandem mass spectrometry (LC/MS/MS). The presence of the adduct in
      urine samples either as the free base or as 2'-deoxynucleoside could help in
      determining the repair mechanism involved when such lesions are produced. A non
      invasive assessment of DNA adducts could also allow for large-scale analyses in
      the population and cancer prevention dietary strategies. METHODS: An LC/MS/MS
      method for the quantitation of O(6)CMG and O(6)CMdG was developed. Urine samples
      collected from healthy volunteers on red meat and vegetarian diets were analysed
      either by direct injection or after purification by solid-phase extraction (SPE).
      A separate LC/MS/MS method for O(6)-methylguanine (O(6)MeG) and O(6)-methyl-2'
      deoxyguanosine (O(6)MedG), which are possible hydrolysis products forming during
      the sample pre-treatment, was also developed. RESULTS: The developed LC/MS/MS
      method allowed the simultaneous measurement of O(6)CMG and O(6)CMdG. The limits
      of detection (LODs) were 0.38 ng/mL for O(6)CMG and 0.18 ng/mL for O(6)CMdG. The
      direct injection analysis of the clinical samples showed low sensitivity due to
      high background signal that was improved by SPE purification. However, the
      concentrations of the adducts in clinical samples were still found to be below
      the LOD. CONCLUSIONS: Novel, reproducible, and accurate LC/MS/MS methods were
      developed for the determination of the urinary content of O(6)CMG and O(6)CMdG,
      and of the possible formation of O(6)MeG and O(6)MedG by decarboxylation.
      Clinical samples from volunteers on different diets were analysed. Further
      studies are required to discover a link between the presence of these biomarkers
      in urine and red meat consumption.

PMID- 24097407
TI  - Deiodination of iodinated aromatic compounds with electrospray ionization mass
      spectrometry.
AB  - RATIONALE: Dehalogenation of iodinated X-ray contrast media (ICM) has been
      reported using electrochemical and bioelectrochemical systems. Correspondingly,
      dehalogenation of aromatic halogens has also been reported in mass spectrometry
      (MS) using different ionization techniques like chemical ionization (CI),
      thermospray, fast-atom bombardment (FAB) and FAB-liquid secondary ionization mass
      spectrometry (LSIMS). The aim of the present work was to study deiodination of
      iodinated aromatic compounds in MS with electrospray ionization (ESI). METHODS:
      The iodinated aromatic compounds were characterized by liquid
      chromatography/tandem mass spectrometry (LC/MS/MS) using a quadrupole time-of
      flight (QTof)-micro MS instrument and ESI in both positive and negative ion mode.
      The effect of mobile phase additives like formic acid, acetic acid,
      trifluoroacetic acid, ammonium formate and ammonium acetate on the negative and
      positive ESI mass spectra of the iodinated aromatic compounds was studied.
      RESULTS: Formic acid and ammonium formate induced deiodination of the iodinated
      aromatic compounds with ESI-MS. Neither acetic acid, trifluoroacetic acid nor
      ammonium acetate induced the deiodination reaction. The effect was most
      pronounced with negative ESI where the HI product of the deiodination reaction
      easily adhered to the aromatic compounds giving rise to HI adducts in the mass
      spectra. The deiodination reaction was shown to take place in the ESI capillary,
      since the extent of the reaction was largely dependent on the capillary voltage.
      The calculated heat of reaction for deiodination of the iodinated aromatic
      compounds was significantly exothermic for formic acid. This was not the case for
      acetic acid and trifluoroacetic acid. CONCLUSIONS: Care should be taken when
      using formic acid as a mobile phase additive in LC/MS analyses of iodinated
      aromatic compounds, since the interpretation of the mass spectra might be
      influenced by potential dehalogenation reactions taking place in the ESI
      capillary.

PMID- 24097408
TI  - Highly sensitive MC-LR detection by matrix-assisted laser desorption/ionization
      time-of-flight mass spectrometry with magnetic mesoporous silica for fast
      extraction.

PMID- 24097409
TI  - Tissue differences in BER-related incision activity and non-specific nuclease
      activity as measured by the comet assay.
AB  - DNA repair mechanisms are important for genome stability and to prevent
      accumulation of DNA damage, which contributes to cellular ageing and cancer
      development. Study of these physiological processes requires robust and practical
      assays to quantify DNA repair capacity. The in vitro comet-based assay is a
      simple, yet reliable, assay for measurement of DNA repair and has been modified
      recently to quantify DNA incision activity in mouse brain and liver. In this
      study, we applied this assay to assess DNA incision activity in other mouse
      tissues, i.e. lung and colon, and found that high, non-specific nuclease activity
      was a problem when measuring DNA incision activity, especially in the colon. We
      tested the utility of multiple optimisation steps including addition of
      aphidicolin, ATP and polyAT and used multiple wash steps, which resulted in
      modest improvements in performance of the assay. Washing the tissues before
      protein extraction and decreasing the protein concentration in the assay were the
      most effective steps in reducing non-specific nuclease activity. Using the comet
      based assay with these further modifications, we found that base excision repair
      incision activity changed with age differently in each tissue. This study shows
      that non-specific nuclease activity in the comet-based assay for DNA repair is
      more pronounced in some tissues than others so care should be taken to optimise
      the protocol when applying the assay to a new tissue. Our data suggest the
      importance of using control cells (noRo cells incubated with extract) in the
      assay to assess for non-specific nuclease activity. In conclusion, the comet
      based DNA repair assay can be easily adapted to study a range of mammalian
      tissues. 

PMID- 24097410
TI  - Resection activity of the Sgs1 helicase alters the affinity of DNA ends for
      homologous recombination proteins in Saccharomyces cerevisiae.
AB  - The RecQ helicase family is critical during DNA damage repair, and mutations in
      these proteins are associated with Bloom, Werner, or Rothmund-Thompson syndromes
      in humans, leading to cancer predisposition and/or premature aging. In the
      budding yeast Saccharomyces cerevisiae, mutations in the RecQ homolog, SGS1,
      phenocopy many of the defects observed in the human syndromes. One challenge to
      studying RecQ helicases is that their disruption leads to a pleiotropic
      phenotype. Using yeast, we show that the separation-of-function allele of SGS1,
      sgs1-D664Delta, has impaired activity at DNA ends, resulting in a resection
      processivity defect. Compromising Sgs1 resection function in the absence of the
      Sae2 nuclease causes slow growth, which is alleviated by making the DNA ends
      accessible to Exo1 nuclease. Furthermore, fluorescent microscopy studies reveal
      that, when Sgs1 resection activity is compromised in sae2Delta cells, Mre11
      repair foci persist. We suggest a model where the role of Sgs1 in end resection
      along with Sae2 is important for removing Mre11 from DNA ends during repair. 

PMID- 24097411
TI  - Sex-specific effects of cis-regulatory variants in Drosophila melanogaster.
AB  - Sexual dimorphism at the level of gene expression is common and well documented,
      but much less is known about how different cis-regulatory alleles interact with
      the different trans-regulatory environments present in males and females. Here we
      show that sex-specific effects of cis-regulatory variants are common in
      Drosophila. 

PMID- 24097412
TI  - APOE modulates the correlation between triglycerides, cholesterol, and CHD
      through pleiotropy, and gene-by-gene interactions.
AB  - Relationship loci (rQTL) exist when the correlation between multiple traits
      varies by genotype. rQTL often occur due to gene-by-gene (G * G) or gene-by
      environmental interactions, making them a powerful tool for detecting G * G. Here
      we present an empirical analysis of apolipoprotein E (APOE) with respect to lipid
      traits and incident CHD leading to the discovery of loci that interact with APOE
      to affect these traits. We found that the relationship between total cholesterol
      (TC) and triglycerides (ln TG) varies by APOE isoform genotype in African
      American (AA) and European-American (EA) populations. The e2 allele is associated
      with strong correlation between ln TG and TC while the e4 allele leads to little
      or no correlation. This led to a priori hypotheses that APOE genotypes affect the
      relationship of TC and/or ln TG with incident CHD. We found that APOE*TC was
      significant (P = 0.016) for AA but not EA while APOE*ln TG was significant for EA
      (P = 0.027) but not AA. In both cases, e2e2 and e2e3 had strong relationships
      between TC and ln TG with CHD while e2e4 and e4e4 results in little or no
      relationship between TC and ln TG with CHD. Using ARIC GWAS data, scans for loci
      that significantly interact with APOE produced four loci for African Americans
      (one CHD, one TC, and two HDL). These interactions contribute to the rQTL
      pattern. rQTL are a powerful tool to identify loci that modify the relationship
      between risk factors and disease and substantially increase statistical power for
      detecting G * G. 

PMID- 24097413
TI  - Strategic addition of an N-linked glycan to a monoclonal antibody improves its
      HIV-1-neutralizing activity.
AB  - Ibalizumab is a humanized monoclonal antibody that binds human CD4--a key
      receptor for HIV--and blocks HIV-1 infection. However, HIV-1 strains with
      mutations resulting in loss of an N-linked glycan from the V5 loop of the
      envelope glycoprotein gp120 are resistant to ibalizumab. Previous structural
      analysis suggests that this glycan fills a void between the gp120 V5 loop and the
      ibalizumab light chain, perhaps causing steric hindrance that disrupts viral
      entry. If this void contributes to HIV-1 resistance to ibalizumab, we reasoned
      that 'refilling' it by engineering an N-linked glycan into the ibalizumab light
      chain at a position spatially proximal to gp120 V5 may restore susceptibility to
      ibalizumab. Indeed, one such ibalizumab variant neutralized 100% of 118 diverse
      HIV-1 strains tested in vitro, including 10 strains resistant to parental
      ibalizumab. These findings demonstrate that the strategic placement of a glycan
      in the variable region of a monoclonal antibody can substantially enhance its
      activity.

PMID- 24097414
TI  - "Rebuilding our community": hearing silenced voices on Aboriginal youth suicide.
AB  - This paper brings forth the voices of adult Aboriginal First Nations community
      members who gathered in focus groups to discuss the problem of youth suicide on
      their reserves. Our approach emphasizes multilevel (e.g., individual, family, and
      broader ecological systems) factors viewed by participants as relevant to youth
      suicide. Wheaton's conceptualization of stressors and Evans-Campbell's multilevel
      classification of the impacts of historical trauma are used as theoretical and
      analytic guides. Thematic analysis of qualitative data transcripts revealed a
      highly complex intersection of stressors, traumas, and social problems seen by
      community members as underlying mechanisms influencing heightened levels of
      Aboriginal youth suicidality. Our multilevel coding approach revealed that
      suicidal behaviors were described by community members largely as a problem with
      deep historical and contemporary structural roots, as opposed to being viewed as
      individualized pathology. 

PMID- 24097415
TI  - Novel association of early onset hepatocellular carcinoma with transaldolase
      deficiency.
AB  - We evaluated a family with a 16-month-old boy with cirrhosis and hepatocellular
      carcinoma and his 30-month-old brother with cirrhosis. After failing to identify
      a diagnosis after routine metabolic evaluation, we utilized a combination of RNA
      Seq and whole exome sequencing to identify a novel homozygous p.Ser171Phe
      Transaldolase (TALDO1) variant in the proband, his brother with cirrhosis, as
      well as a clinically asymptomatic older 8-year-old brother. Metabolite analysis
      and enzymatic testing of TALDO1 demonstrated elevated ribitol, sedoheptitol, and
      sedoheptulose-7P, and lack of activity of TALDO1 in the three children homozygous
      for the p.Ser171Phe mutation. Our findings expand the phenotype of transaldolase
      deficiency to include early onset hepatocellular carcinoma in humans and
      demonstrate that, even within the same family, individuals with the same
      homozygous mutation demonstrate a wide range of phenotypes. 

PMID- 24097416
TI  - Cystinosis with sclerotic bone lesions.
AB  - A 26-year-old male with nephropathic cystinosis treated with cysteamine and renal
      transplantation presented for evaluation of multiple sclerotic bone lesions,
      which were an incidental finding on chest computerized tomography. These lesions
      were in a pattern consistent with osteoblastic metastases. He did not have a
      history of clinically significant hyperparathyroidism or cytopenias either
      preceding or following his transplant. Bone and tumor markers (including alkaline
      phosphatase and calcium) were all normal. A percutaneous bone biopsy of the
      lesions showed changes compatible with cystine deposition. Our case demonstrates
      that sclerotic bone lesions can be a feature of cystinosis in patients with
      normal parathyroid function and that significant bone marrow infiltration with
      cystine can be present even in the absence of cytopenias. 

PMID- 24097417
TI  - Endovascular management of acute limb ischemia.
AB  - Acute limb ischemia (ALI) is defined as a sudden decrease (<14 days) in limb
      perfusion causing a potential threat to limb viability. Endovascular treatment of
      ALI is an effective and appropriate primary treatment strategy in patients with a
      viable acutely ischemic limb due to a recent arterial occlusion. We present a
      case of acute limb ischemia and discuss percutaneous interventional treatment
      strategies including catheter-directed thrombolysis, rheolytic thrombectomy, and
      utilization of distal protection devices. 

PMID- 24097418
TI  - Accuracy of conventional oximetry for flow estimation in patients with superior
      cavopulmonary connection: a comparison with phase-contrast cardiac MRI.
AB  - BACKGROUND: Cardiac catheterization is routinely used as a diagnostic tool in
      single ventricle patients with superior cavopulmonary connection. This physiology
      presents inherent challenges in applying the Fick principle to estimate flow. We
      sought to quantitatively define the error in oximetry-derived flow parameters
      using phase-contrast cardiac MRI (CMR) as a reference. METHODS AND RESULTS:
      Thirty patients with superior cavopulmonary connection who underwent combined CMR
      and catheterization between July 2008 and June 2012 were retrospectively
      analyzed. Estimates of flow and resistance calculated using the Fick equation
      were compared with CMR measurements. Oximetry underestimated CMR-measured
      pulmonary blood flow (Qp) by an average of 1.1 L/min per m(2) or 32% of the CMR
      value (P<0.0001). Oximetry overestimated systemic blood flow (Qs) by an average
      of 0.5 L/min per m(2) or 15% of the CMR value (P=0.009). There was no correlation
      between the Qp:Qs ratio derived by Fick and that measured by CMR (rho(c)=0.01).
      The error in the Fick Qp correlated moderately with the measured systemic-to
      pulmonary arterial collateral flow (r=0.39). The median total oxygen consumption
      calculated using combined CMR and oximetry data was 173 mL/min per m(2), higher
      than the assumed values used to calculate flows by the Fick equation. The upper
      body circulation received on average 51% of systemic blood flow while conducting
      only 39% of total body metabolism. CONCLUSIONS: Fick-derived estimates of flow
      are inherently unreliable in patients with superior cavopulmonary connections.
      Integrating flows measured by CMR and pressures measured by catheter will provide
      the best characterization of superior cavopulmonary connection physiology.

PMID- 24097419
TI  - Impact of net atrioventricular compliance on clinical outcome in mitral stenosis.
AB  - BACKGROUND: Net atrioventricular compliance (Cn) has been reported to be an
      important determinant of pulmonary hypertension in mitral stenosis (MS). We
      hypothesized that it may be useful in assessing prognosis because Cn reflects
      hemodynamic consequences of MS. To date, limited data with an assumed Cn cutoff
      have indicated the need for larger prospective studies. This prospective study
      was designed to determine the impact of Cn on clinical outcome and its
      contribution to pulmonary pressure in MS. In addition, we aimed to identify a
      cutoff value of Cn for outcome prediction in this setting. METHODS AND RESULTS: A
      total of 128 patients with rheumatic MS without other significant valve disease
      were prospectively enrolled. Comprehensive echocardiography was performed and
      Doppler-derived Cn estimated using a previously validated equation. The end point
      was either mitral valve intervention or death. Cn was an important predictor of
      pulmonary pressure, regardless of classic measures of MS severity. During a
      median follow-up of 22 months, the end point was reached in 45 patients (35%).
      Baseline Cn predicted outcome, adding prognostic information beyond that provided
      by mitral valve area and functional status. Cn <=4 mL/mm Hg best predicted
      unfavorable outcome in derivation and validation sets. A subgroup analysis
      including only initially asymptomatic patients with moderate to severe MS without
      initial indication for intervention (40.6% of total) demonstrated that baseline
      Cn predicted subsequent adverse outcome even after adjustment for classic
      measures of hemodynamic MS severity (hazard ratio, 0.33; 95% confidence interval,
      0.14-0.79; P=0.013). CONCLUSIONS: Cn contributes to pulmonary hypertension beyond
      stenosis severity itself. In a wide spectrum of MS severity, Cn is a powerful
      predictor of adverse outcome, adding prognostic value to clinical data and mitral
      valve area. Importantly, baseline Cn predicts a progressive course with
      subsequent need for intervention in initially asymptomatic patients. Cn
      assessment therefore has potential value for clinical risk stratification and
      monitoring in MS patients.

PMID- 24097420
TI  - Occult cardiotoxicity in childhood cancer survivors exposed to anthracycline
      therapy.
AB  - BACKGROUND: More than 50% of >270 000 childhood cancer survivors in the United
      States have been treated with anthracyclines and are therefore at risk of
      developing cardiotoxicity. Cardiac magnetic resonance (CMR) has demonstrated
      utility to detect diffuse interstitial fibrosis and changes in regional
      myocardial function. We hypothesized that CMR would identify occult
      cardiotoxicity characterized by structural and functional myocardial
      abnormalities in a cohort of asymptomatic pediatric cancer survivors with normal
      global systolic function. METHODS AND RESULTS: Forty-six long-term childhood
      cancer survivors with a cumulative anthracycline dose >=200 mg/m(2) and normal
      systolic function were studied 2.5 to 26.9 years after anthracycline exposure.
      Subjects underwent transthoracic echocardiography, CMR with routine cine
      acquisition, tissue characterization, and left ventricular strain analysis using
      a modified 16-segment model. Extracellular volume was measured in 27 subjects,
      all of whom were late gadolinium enhancement negative. End-systolic fiber stress
      was elevated in 45 of 46 subjects. Low average circumferential strain magnitude
      (epsiloncc) -14.9+/-1.4; P<0.001, longitudinal strain magnitude (epsilonll) 
      13.5+/-1.9; P<0.001, and regional peak circumferential strain were seen in
      multiple myocardial segments, despite normal global systolic function by
      transthoracic echocardiography and CMR. The mean T1 values of the myocardium were
      significantly lower than that of control subjects at 20 minutes (458+/-69 versus
      487+/-44 milliseconds; P=0.01). Higher mean extracellular volume was observed in
      female subjects (0.34 versus 0.22; P=0.01). CONCLUSIONS: Asymptomatic
      postchemotherapy pediatric patients have abnormal myocardial characteristics and
      strain parameters by CMR despite normal global cardiac function by standard
      transthoracic echocardiography and CMR measures.

PMID- 24097421
TI  - Magnetic resonance imaging investigation of macrophages in acute cardiac
      allograft rejection after heart transplantation.
AB  - BACKGROUND: Current immunosuppressive therapy after heart transplantation either
      generally suppresses the recipient's entire immune system or is mainly targeting
      T-lymphocytes. Monocytes/macrophages are recognized as a hallmark of acute
      allograft rejection, but the roles that they play are not well characterized in
      vivo, because the tools for accessing in situ macrophage infiltration are
      lacking. In this study, we used MRI to investigate the role of macrophages in
      acute heart allograft rejection by cellular and functional MRI with selectively
      depleted systemic macrophages without affecting other leukocyte population, as
      well as to explore the possibility that macrophages could be an alternative
      therapeutic target. METHODS AND RESULTS: A rodent heterotopic working heart-lung
      transplantation model was used for studying acute allograft rejection. Systemic
      macrophages were selectively depleted by treating recipient animals with
      clodronate-liposomes. Macrophage infiltration in the graft hearts was monitored
      by cellular MRI with in vivo ultrasmall superparamagnetic iron oxide particles
      labeling. Graft heart function was evaluated by tagging MRI followed by strain
      analysis. Clodronate-liposome treatment depletes circulating
      monocytes/macrophages in transplant recipients, and both cellular MRI and
      pathological examinations indicate a significant reduction in macrophage
      accumulation in the rejecting allograft hearts. In clodronate-liposome-treated
      group, allograft hearts exhibited preserved tissue integrity, partially reversed
      functional deterioration, and prolonged graft survival, compared with untreated
      controls. CONCLUSIONS: Cardiac cellular and functional MRI is a powerful tool to
      explore the roles of targeted immune cells in vivo. Our results indicate that
      macrophages are essential in acute cardiac allograft rejection, and selective
      depletion of macrophages with clodronate-liposomes protects hearts against
      allograft rejection, suggesting a potential therapeutic avenue. Our findings show
      that there is a finite risk of forming an intraventricular mass, presumably from
      the cellular debris or lipid material. Further optimization of the dosing
      protocol is necessary before clinical applications.

PMID- 24097422
TI  - Multicenter study comparing shunt type in the norwood procedure for single
      ventricle lesions: three-dimensional echocardiographic analysis.
AB  - BACKGROUND: The Pediatric Heart Network's Single Ventricle Reconstruction (SVR)
      trial randomized infants with single right ventricles (RVs) undergoing a Norwood
      procedure to a modified Blalock-Taussig or RV-to-pulmonary artery shunt. This
      report compares RV parameters in the 2 groups using 3-dimensional
      echocardiography. METHODS AND RESULTS: Three-dimensional echocardiography studies
      were obtained at 10 of 15 SVR centers. Of the 549 subjects, 314 underwent 3
      dimensional echocardiography studies at 1 to 4 time points (pre-Norwood, post
      Norwood, pre-stage II, and 14 months) for a total of 757 3-dimensional
      echocardiography studies. Of these, 565 (75%) were acceptable for analysis. RV
      volume, mass, mass:volume ratio, ejection fraction, and severity of tricuspid
      regurgitation did not differ by shunt type. RV volumes and mass did not change
      after the Norwood, but increased from pre-Norwood to pre-stage II (end-diastolic
      volume [milliliters]/body surface area [BSA](1.3), end-systolic volume
      [milliliters]/BSA(1.3), and mass [grams]/BSA(1.3) mean difference [95% confidence
      interval]=25.0 [8.7-41.3], 19.3 [8.3-30.4], and 17.9 [7.3-28.5], then decreased
      by 14 months (end-diastolic volume/BSA(1.3), end-systolic volume/BSA(1.3), and
      mass/BSA(1.3) mean difference [95% confidence interval]=-24.4 [-35.0 to -13.7], 
      9.8 [-17.9 to -1.7], and -15.3 [-22.0 to -8.6]. Ejection fraction decreased from
      pre-Norwood to pre-stage II (mean difference [95% confidence interval]=-3.7 [-6.9
      to -0.5]), but did not decrease further by 14 months. CONCLUSIONS: We found no
      statistically significant differences between study groups in 3-dimensional
      echocardiography measures of RV size and function, or magnitude of tricuspid
      regurgitation. Volume unloading was seen after stage II, as expected, but
      ejection fraction did not improve. This study provides insights into the
      remodeling of the operated univentricular RV in infancy.

PMID- 24097423
TI  - Long-term cumulative depressive symptom burden and risk of cognitive decline and
      dementia among very old women.
AB  - BACKGROUND: Depressive symptoms and cognitive outcomes are strongly interrelated.
      Despite that rates of depressive symptoms fluctuate during late life, little is
      known about the impact of long-term cumulative depressive symptom burden on
      cognitive decline and dementia in older adults. This study examines the
      association of nearly 20 years of cumulative depressive symptoms with cognitive
      outcomes in a cohort of older women. METHODS: We assessed depressive symptoms in
      7,240 women using the Geriatric Depression scale (GDS) at serial visits. We used
      a Poisson model with random slopes to estimate GDS trajectories for each
      participant from baseline to death or end of follow-up, and then characterized
      depressive symptom burden by quartile of the area under the curve. We assessed
      cognitive outcomes using repeated measures of the Mini-Mental State Examination
      (MMSE) and Trails B score over 20 years, Year-20 neuropsychological test battery,
      and adjudicated dementia and mild cognitive impairment (MCI). RESULTS: Adjusting
      for potential confounders, compared with women in the lowest quartile of
      cumulative depressive symptoms burden, women in the highest quartile had 21% more
      MMSE errors over time (95% CI = 17%, 26%), 20% worse Trails B score over time
      (95% CI = 17%, 23%), worse scores on most of the Year-20 cognitive tests, and a
      twofold greater likelihood of developing dementia or MCI (95% CI = 1.48, 3.11).
      CONCLUSIONS: Long-term cumulative depressive symptom burden was associated with
      cognitive decline and risk of dementia or MCI. Older adults with a history of
      depression should be closely monitored for recurrent episodes or unresolved
      depressive symptoms as well as any cognitive deficits.

PMID- 24097424
TI  - Lipid-lowering drugs associated with slower motor decline in the elderly adults.
AB  - BACKGROUND: Vascular risk factors contribute to motor decline in the elderly
      persons. We investigated the relationship between lipid-lowering drugs (LLDs) use
      and decline in walking speed (WS) in older adults. METHODS: Data on 4,009
      community-dwelling men and women, aged >=65 years at baseline, are drawn from the
      Dijon (France) center of the Three-City study. "Fast" WS was assessed over 6 m at
      baseline and at 4, 6, 8, and 10 years of follow-up. Mixed linear models were used
      to determine the relationship between LLDs and change in WS over the follow-up.
      RESULTS: At baseline, 1,295 (32%) participants used LLDs (statins, n = 643;
      fibrates, n = 652); mean fast WS was 152.9cm/s and not significantly different
      between LLDs users and nonusers. In models adjusted for age, sex, cholesterol
      level, and other covariates, WS decline was 25% slower in LLDs users (difference
      with nonusers: 0.58cm/s/y, 95% CI: 0.30, 0.86; p < .001). Both fibrates and
      statins were associated with slower decline, but only the effect of statins was
      robust in analyses that took missing values into account. The beneficial effect
      was more pronounced in those on LLDs continuously over the follow-up. CONCLUSION:
      Fast WS declined less in those on LLDs, suggesting that the effect of LLDs,
      statins in particular, extend beyond that on cardiovascular disease in the
      elderly persons. However, these effects were modest and their clinical relevance
      is unclear.

PMID- 24097426
TI  - Insulin resistance protects the heart from fuel overload in dysregulated
      metabolic states.
AB  - Reversing impaired insulin sensitivity has been suggested as treatment for heart
      failure. However, recent clinical evidence suggests the opposite. Here we present
      a line of reasoning in support of the hypothesis that insulin resistance protects
      the heart from the consequences of fuel overload in the dysregulated metabolic
      state of obesity and diabetes. We discuss pathways of myocardial fuel toxicity,
      as well as several layers of defense against fuel overload. Our reassessment of
      the literature suggests that in the heart, insulin-sensitizing agents result in
      an elimination of some of the defenses, leading to cytotoxic damage. In contrast,
      a normalization of fuel supply should either prevent or reverse the process.
      Taken together, we offer a new perspective on insulin resistance of the heart. 

PMID- 24097427
TI  - Intrauterine growth restriction is associated with cardiac ultrastructural and
      gene expression changes related to the energetic metabolism in a rabbit model.
AB  - Intrauterine growth restriction (IUGR) affects 7-10% of pregnancies and is
      associated with cardiovascular remodeling and dysfunction, which persists into
      adulthood. The underlying subcellular remodeling and cardiovascular programming
      events are still poorly documented. Cardiac muscle is central in the fetal
      adaptive mechanism to IUGR given its high energetic demands. The energetic
      homeostasis depends on the correct interaction of several molecular pathways and
      the adequate arrangement of intracellular energetic units (ICEUs), where
      mitochondria interact with the contractile machinery and the main cardiac ATPases
      to enable a quick and efficient energy transfer. We studied subcellular cardiac
      adaptations to IUGR in an experimental rabbit model. We evaluated the
      ultrastructure of ICEUs with transmission electron microscopy and observed an
      altered spatial arrangement in IUGR, with significant increases in cytosolic
      space between mitochondria and myofilaments. A global decrease of mitochondrial
      density was also observed. In addition, we conducted a global gene expression
      profile by advanced bioinformatics tools to assess the expression of genes
      involved in the cardiomyocyte energetic metabolism and identified four gene
      modules with a coordinated over-representation in IUGR: oxygen homeostasis (GO:
      0032364), mitochondrial respiratory chain complex I (GO:0005747), oxidative
      phosphorylation (GO: 0006119), and NADH dehydrogenase activity (GO:0003954).
      These findings might contribute to changes in energetic homeostasis in IUGR. The
      potential persistence and role of these changes in long-term cardiovascular
      programming deserves further investigation. 

PMID- 24097425
TI  - Role of 20-HETE, TRPC channels, and BKCa in dysregulation of pressure-induced
      Ca2+ signaling and myogenic constriction of cerebral arteries in aged
      hypertensive mice.
AB  - Hypertension in the elderly substantially increases the risk of stroke and
      vascular cognitive impairment in part due to an impaired functional adaptation of
      aged cerebral arteries to high blood pressure. To elucidate the mechanisms
      underlying impaired autoregulatory protection in aging, hypertension was induced
      in young (3 mo) and aged (24 mo) C57BL/6 mice by chronic infusion of angiotensin
      II and pressure-induced changes in smooth muscle cell (SMC) intracellular Ca(2+)
      concentration ([Ca(2+)]i) and myogenic constriction of middle cerebral arteries
      (MCA) were assessed. In MCAs from young hypertensive mice, pressure-induced
      increases in vascular SMC [Ca(2+)]i and myogenic tone were increased, and these
      adaptive responses were inhibited by the cytochrome P-450 omega-hydroxylase
      inhibitor HET0016 and the transient receptor potential (TRP) channel blocker
      SKF96365. Administration of 20- hydroxyeicosatetraenoic acid (HETE) increased SMC
      [Ca(2+)]i and constricted MCAs, and these responses were inhibited by SKF96365.
      MCAs from aged hypertensive mice did not show adaptive increases in pressure
      induced calcium signal and myogenic tone and responses to HET0016 and SKF96365
      were blunted. Inhibition of large-conductance Ca(2+)-activated K(+) (BK) channels
      by iberiotoxin enhanced SMC [Ca(2+)]i and myogenic constriction in MCAs of young
      normotensive animals, whereas it was without effect in MCAs of young hypertensive
      mice. Iberiotoxin did not restore myogenic adaptation in MCAs of aged
      hypertensive mice. Thus functional maladaptation of aged cerebral arteries to
      hypertension is due to the dysregulation of pressure-induced 20-HETE and TRP
      channel-mediated SMC calcium signaling, whereas overactivation of BK channels is
      unlikely to play a role in this phenomenon. 

PMID- 24097428
TI  - Inhibition of NF-kappaB activation by a novel IKK inhibitor reduces the severity
      of experimental autoimmune myocarditis via suppression of T-cell activation.
AB  - NF-kappaB, which is activated by the inhibitor of NF-kappaB kinase (IKK), is
      involved in the progression of inflammatory disease. However, the effect of IKK
      inhibition on the progression of myocarditis is unknown. We examined the effect
      of IKK inhibition on the progression of myocarditis. Lewis rats were immunized
      with porcine cardiac myosin to induce experimental autoimmune myocarditis (EAM).
      We administered the IKK inhibitor (IMD-0354; 15 mg.kg(-1).day(-1)) or vehicle to
      EAM rats daily. Hearts were harvested 21 days after immunization. Although the
      untreated EAM group showed increased heart weight-to-body weight ratio, and
      severe myocardial damage, these changes were attenuated in the IKK inhibitor
      treated group. Moreover, IKK inhibitor administration significantly reduced NF
      kappaB activation and mRNA expression of IFN-gamma, IL-2, and monocyte
      chemoattractant protein-1 in myocardium compared with vehicle administration. In
      vitro study showed that the IKK inhibitor treatment inhibited T-cell
      proliferation and Th1 cytokines production induced by myosin stimulation. The IKK
      inhibitor ameliorated EAM by suppressing inflammatory reactions via suppression
      of T-cell activation. 

PMID- 24097429
TI  - The mouse aortocaval fistula recapitulates human arteriovenous fistula
      maturation.
AB  - Several models of arteriovenous fistula (AVF) have excellent patency and help in
      understanding the mechanisms of venous adaptation to the arterial environment.
      However, these models fail to exhibit either maturation failure or fail to
      develop stenoses, both of which are critical modes of AVF failure in human
      patients. We used high-resolution Doppler ultrasound to serially follow mice with
      AVFs created by direct 25-gauge needle puncture. By day 21, 75% of AVFs dilate,
      thicken, and increase flow, i.e., mature, and 25% fail due to immediate
      thrombosis or maturation failure. Mature AVF thicken due to increased amounts of
      smooth muscle cells. By day 42, 67% of mature AVFs remain patent, but 33% of AVFs
      fail due to perianastomotic thickening. These results show that the mouse
      aortocaval model has an easily detectable maturation phase in the first 21 days
      followed by a potential failure phase in the subsequent 21 days. This model is
      the first animal model of AVF to show a course that recapitulates aspects of
      human AVF maturation. 

PMID- 24097430
TI  - Central control of cardiovascular function during sleep.
AB  - There is increasing evidence that cardiovascular control during sleep is relevant
      for cardiovascular risk. This evidence warrants increased experimental efforts to
      understand the physiological mechanisms of such control. This review summarizes
      current knowledge on autonomic features of sleep states [non-rapid-eye-movement
      sleep (NREMS) and rapid-eye-movement sleep (REMS)] and proposes some testable
      hypotheses concerning the underlying neural circuits. The physiological reduction
      of blood pressure (BP) during the night (BP dipping phenomenon) is mainly caused
      by generalized cardiovascular deactivation and baroreflex resetting during NREMS,
      which, in turn, are primarily a consequence of central autonomic commands.
      Central commands during NREMS may involve the hypothalamic ventrolateral preoptic
      area, central thermoregulatory and central baroreflex pathways, and command
      neurons in the pons and midbrain. During REMS, opposing changes in vascular
      resistance in different regional beds have the net effect of increasing BP
      compared with that of NREMS. In addition, there are transient increases in BP and
      baroreflex suppression associated with bursts of brain and skeletal muscle
      activity during REMS. These effects are also primarily a consequence of central
      autonomic commands, which may involve the midbrain periaqueductal gray, the
      sublaterodorsal and peduncular pontine nuclei, and the vestibular and raphe
      obscurus medullary nuclei. A key role in permitting physiological changes in BP
      during sleep may be played by orexin peptides released by hypothalamic neurons,
      which target the postulated neural pathways of central autonomic commands during
      NREMS and REMS. Experimental verification of these hypotheses may help reveal
      which central neural pathways and mechanisms are most essential for sleep-related
      changes in cardiovascular function. 

PMID- 24097431
TI  - Protein nitration impairs the myogenic tone of rat middle cerebral arteries in
      both ischemic and nonischemic hemispheres after ischemic stroke.
AB  - The myogenic response is crucial for maintaining vascular resistance to achieve
      constant perfusion during pressure fluctuations. Reduced cerebral blood flow has
      been reported in ischemic and nonischemic hemispheres after stroke. Ischemia
      reperfusion injury and the resulting oxidative stress impair myogenic responses
      in the ischemic hemisphere. Yet, the mechanism by which ischemia-reperfusion
      affects the nonischemic side is still undetermined. The goal of the present study
      was to determine the effect of ischemia-reperfusion injury on the myogenic
      reactivity of cerebral vessels from both hemispheres and whether protein
      nitration due to excess peroxynitrite production is the underlying mechanism of
      loss of tone. Male Wistar rats were subjected to sham operation or 30-min middle
      cerebral artery occlusion/45-min reperfusion. Rats were administered saline, the
      peroxynitrite decomposition catalyst 5,10,15,20-tetrakis(4
      sulfonatophenyl)prophyrinato iron (III), or the nitration inhibitor epicatechin
      at reperfusion. Middle cerebral arteries isolated from another set of control
      rats were exposed to ex vivo oxygen-glucose deprivation with and without
      glycoprotein 91 tat (NADPH oxidase inhibitor) or N(omega)-nitro-l-arginine methyl
      ester. Myogenic tone and nitrotyrosine levels were determined. Ischemia
      reperfusion injury impaired the myogenic tone of vessels in both hemispheres
      compared with the sham group (P < 0.001). Vessels exposed to ex vivo oxygen
      glucose deprivation experienced a similar loss of myogenic tone. Inhibition of
      peroxynitrite parent radicals significantly improved the myogenic tone.
      Peroxynitrite scavenging or inhibition of nitration improved the myogenic tone of
      vessels from ischemic (P < 0.001 and P < 0.05, respectively) and nonischemic (P <
      0.01 and P < 0.05, respectively) hemispheres. Nitration was significantly
      increased in both hemispheres versus the sham group and was normalized with
      epicatechin treatment. In conclusion, ischemia-reperfusion injury impairs vessel
      reactivity in both hemispheres via nitration. We suggest that sham operation
      rather than the nonischemic side should be used as a control in preclinical
      stroke studies. 

PMID- 24097432
TI  - Chronic intermittent hypoxia increases sympathetic control of blood pressure:
      role of neuronal activity in the hypothalamic paraventricular nucleus.
AB  - Like humans with sleep apnea, rats exposed to chronic intermittent hypoxia (CIH)
      experience arterial hypoxemias and develop hypertension characterized by
      exaggerated sympathetic nerve activity (SNA). To gain insights into the poorly
      understood mechanisms that initiate sleep apnea/CIH-associated hypertension,
      experiments were performed in rats exposed to CIH for only 7 days. Compared with
      sham-treated normoxic control rats, CIH-exposed rats (n = 8 rats/group) had
      significantly increased hematocrit (P < 0.001) and mean arterial pressure (MAP; P
      < 0.05). Blockade of ganglionic transmission caused a significantly (P < 0.05)
      greater reduction of MAP in rats exposed to CIH than control rats (n = 8
      rats/group), indicating a greater contribution of SNA in the support of MAP even
      at this early stage of CIH hypertension. Chemical inhibition of neuronal
      discharge in the hypothalamic paraventricular nucleus (PVN) (100 pmol muscimol)
      had no effect on renal SNA but reduced lumbar SNA (P < 0.005) and MAP (P < 0.05)
      more in CIH-exposed rats (n = 8) than control rats (n = 7), indicating that CIH
      increased the contribution of PVN neuronal activity in the support of lumbar SNA
      and MAP. Because CIH activates brain regions controlling body fluid homeostasis,
      the effects of internal carotid artery injection of hypertonic saline were tested
      and determined to increase lumbar SNA more (P < 0.05) in CIH-exposed rats than in
      control rats (n = 9 rats/group). We conclude that neurogenic mechanisms are
      activated early in the development of CIH hypertension such that elevated MAP
      relies on increased sympathetic tonus and ongoing PVN neuronal activity. The
      increased sensitivity of Na(+)/osmosensitive circuitry in CIH-exposed rats
      suggests that early neuroadaptive responses among body fluid regulatory neurons
      could contribute to the initiation of CIH hypertension. 

PMID- 24097433
TI  - De novo prediction of DNA-binding specificities for Cys2His2 zinc finger
      proteins.
AB  - Proteins with sequence-specific DNA binding function are important for a wide
      range of biological activities. De novo prediction of their DNA-binding
      specificities from sequence alone would be a great aid in inferring cellular
      networks. Here we introduce a method for predicting DNA-binding specificities for
      Cys2His2 zinc fingers (C2H2-ZFs), the largest family of DNA-binding proteins in
      metazoans. We develop a general approach, based on empirical calculations of
      pairwise amino acid-nucleotide interaction energies, for predicting position
      weight matrices (PWMs) representing DNA-binding specificities for C2H2-ZF
      proteins. We predict DNA-binding specificities on a per-finger basis and merge
      predictions for C2H2-ZF domains that are arrayed within sequences. We test our
      approach on a diverse set of natural C2H2-ZF proteins with known binding
      specificities and demonstrate that for >85% of the proteins, their predicted PWMs
      are accurate in 50% of their nucleotide positions. For proteins with several zinc
      finger isoforms, we show via case studies that this level of accuracy enables us
      to match isoforms with their known DNA-binding specificities. A web server for
      predicting a PWM given a protein containing C2H2-ZF domains is available online
      at http://zf.princeton.edu and can be used to aid in protein engineering
      applications and in genome-wide searches for transcription factor targets. 

PMID- 24097434
TI  - Transition-state stabilization in Escherichia coli ribonuclease P RNA-mediated
      cleavage of model substrates.
AB  - We have used model substrates carrying modified nucleotides at the site
      immediately 5' of the canonical RNase P cleavage site, the -1 position, to study
      Escherichia coli RNase P RNA-mediated cleavage. We show that the nucleobase at -1
      is not essential but its presence and identity contribute to efficiency, fidelity
      of cleavage and stabilization of the transition state. When U or C is present at 
      1, the carbonyl oxygen at C2 on the nucleobase contributes to transition-state
      stabilization, and thus acts as a positive determinant. For substrates with
      purines at -1, an exocyclic amine at C2 on the nucleobase promotes cleavage at an
      alternative site and it has a negative impact on cleavage at the canonical site.
      We also provide new insights into the interaction between E. coli RNase P RNA and
      the -1 residue in the substrate. Our findings will be discussed using a model
      where bacterial RNase P cleavage proceeds through a conformational-assisted
      mechanism that positions the metal(II)-activated H2O for an in-line attack on the
      phosphorous atom that leads to breakage of the phosphodiester bond. 

PMID- 24097435
TI  - PRMT5-mediated histone H4 arginine-3 symmetrical dimethylation marks chromatin at
      G + C-rich regions of the mouse genome.
AB  - Symmetrical dimethylation on arginine-3 of histone H4 (H4R3me2s) has been
      reported to occur at several repressed genes, but its specific regulation and
      genomic distribution remained unclear. Here, we show that the type-II protein
      arginine methyltransferase PRMT5 controls H4R3me2s in mouse embryonic fibroblasts
      (MEFs). In these differentiated cells, we find that the genome-wide pattern of
      H4R3me2s is highly similar to that in embryonic stem cells. In both the cell
      types, H4R3me2s peaks are detected predominantly at G + C-rich regions. Promoters
      are consistently marked by H4R3me2s, independently of transcriptional activity.
      Remarkably, H4R3me2s is mono-allelic at imprinting control regions (ICRs), at
      which it marks the same parental allele as H3K9me3, H4K20me3 and DNA methylation.
      These repressive chromatin modifications are regulated independently, however,
      since PRMT5-depletion in MEFs resulted in loss of H4R3me2s, without affecting
      H3K9me3, H4K20me3 or DNA methylation. Conversely, depletion of ESET (KMT1E) or
      SUV420H1/H2 (KMT5B/C) affected H3K9me3 and H4K20me3, respectively, without
      altering H4R3me2s at ICRs. Combined, our data indicate that PRMT5-mediated
      H4R3me2s uniquely marks the mammalian genome, mostly at G + C-rich regions, and
      independently from transcriptional activity or chromatin repression. Furthermore,
      comparative bioinformatics analyses suggest a putative role of PRMT5-mediated
      H4R3me2s in chromatin configuration in the nucleus. 

PMID- 24097436
TI  - Cotranscriptional recruitment of yeast TRAMP complex to intronic sequences
      promotes optimal pre-mRNA splicing.
AB  - Most unwanted RNA transcripts in the nucleus of eukaryotic cells, such as
      splicing-defective pre-mRNAs and spliced-out introns, are rapidly degraded by the
      nuclear exosome. In budding yeast, a number of these unwanted RNA transcripts,
      including spliced-out introns, are first recognized by the nuclear exosome
      cofactor Trf4/5p-Air1/2p-Mtr4p polyadenylation (TRAMP) complex before subsequent
      nuclear-exosome-mediated degradation. However, it remains unclear when spliced
      out introns are recognized by TRAMP, and whether TRAMP may have any potential
      roles in pre-mRNA splicing. Here, we demonstrated that TRAMP is
      cotranscriptionally recruited to nascent RNA transcripts, with particular
      enrichment at intronic sequences. Deletion of TRAMP components led to further
      accumulation of unspliced pre-mRNAs even in a yeast strain defective in nuclear
      exosome activity, suggesting a novel stimulatory role of TRAMP in splicing. We
      also uncovered new genetic and physical interactions between TRAMP and several
      splicing factors, and further showed that TRAMP is required for optimal
      recruitment of the splicing factor Msl5p. Our study provided the first evidence
      that TRAMP facilitates pre-mRNA splicing, and we interpreted this as a fail-safe
      mechanism to ensure the cotranscriptional recruitment of TRAMP before or during
      splicing to prepare for the subsequent targeting of spliced-out introns to rapid
      degradation by the nuclear exosome. 

PMID- 24097437
TI  - A highly sensitive in vivo footprinting technique for condition-dependent
      identification of cis elements.
AB  - Knowing which regions of a gene are targeted by transcription factors during
      induction or repression is essential for understanding the mechanisms responsible
      for regulation. Therefore, we re-designed the traditional in vivo footprinting
      method to obtain a highly sensitive technique, which allows identification of the
      cis elements involved in condition-dependent gene regulation. Data obtained
      through DMS methylation, HCl DNA cleavage and optimized ligation-mediated PCR
      using fluorescent labelling followed by capillary gel electrophoresis are
      analysed by ivFAST. In this work we have developed this command line-based
      program, which is designed to ensure automated and fast data processing and
      visualization. The new method facilitates a quantitative, high-throughput
      approach because it enables the comparison of any number of in vivo footprinting
      results from different conditions (e.g. inducing, repressing, de-repressing) to
      one another by employing an internal standard. For validation of the method the
      well-studied upstream regulatory region of the Trichoderma reesei xyn1
      (endoxylanase 1) gene was used. Applying the new method we could identify the
      motives involved in condition-dependent regulation of the cbh2 (cellobiohydrolase
      2) and xyn2 (endoxylanase 2) genes. 

PMID- 24097438
TI  - Epstein-Barr virus-mediated transformation of B cells induces global chromatin
      changes independent to the acquisition of proliferation.
AB  - Epstein-Barr virus (EBV) infects and transforms human primary B cells inducing
      indefinite proliferation. To investigate the potential participation of chromatin
      mechanisms during the EBV-mediated transformation of resting B cells we performed
      an analysis of global changes in histone modifications. We observed a remarkable
      decrease and redistribution of heterochromatin marks including H4K20me3, H3K27me3
      and H3K9me3. Loss of H4K20me3 and H3K9me3 occurred at constitutive
      heterochromatin repeats. For H3K27me3 and H3K9me3, comparison of ChIP-seq data
      revealed a decrease in these marks in thousands of genes, including clusters of
      HOX and ZNF genes, respectively. Moreover, DNase-seq data comparison between
      resting and EBV-transformed B cells revealed increased endonuclease accessibility
      in thousands of genomic sites. We observed that both loss of H3K27me3 and
      increased accessibility are associated with transcriptional activation. These
      changes only occurred in B cells transformed with EBV and not in those stimulated
      to proliferate with CD40L/IL-4, despite their similarities in the cell pathways
      involved and proliferation rates. In fact, B cells infected with EBNA-2 deficient
      EBV, which have much lower proliferation rates, displayed similar decreases for
      heterochromatic histone marks. Our study describes a novel phenomenon related to
      transformation of B cells, and highlights its independence of the pure
      acquisition of proliferation. 

PMID- 24097439
TI  - Optimal duration of dual antiplatelet therapy after drug-eluting stent
      implantation: a randomized, controlled trial.
AB  - BACKGROUND: The risks and benefits of long-term dual antiplatelet therapy remain
      unclear. METHODS AND RESULTS: This prospective, multicenter, open-label,
      randomized comparison trial was conducted in 24 clinical centers in Korea. In
      total, 5045 patients who received drug-eluting stents and were free of major
      adverse cardiovascular events and major bleeding for at least 12 months after
      stent placement were enrolled between July 2007 and July 2011. Patients were
      randomized to receive aspirin alone (n=2514) or clopidogrel plus aspirin
      (n=2531). The primary end point was a composite of death resulting from cardiac
      causes, myocardial infarction, or stroke 24 months after randomization. At 24
      months, the primary end point occurred in 57 aspirin-alone group patients (2.4%)
      and 61 dual-therapy group patients (2.6%; hazard ratio, 0.94; 95% confidence
      interval, 0.66-1.35; P=0.75). The 2 groups did not differ significantly in terms
      of the individual risks of death resulting from any cause, myocardial infarction,
      stent thrombosis, or stroke. Major bleeding occurred in 24 (1.1%) and 34 (1.4%)
      of the aspirin-alone group and dual-therapy group patients, respectively (hazard
      ratio, 0.71; 95% confidence interval, 0.42-1.20; P=0.20). CONCLUSIONS: Among
      patients who were on 12-month dual antiplatelet therapy without complications, an
      additional 24 months of dual antiplatelet therapy versus aspirin alone did not
      reduce the risk of the composite end point of death from cardiac causes,
      myocardial infarction, or stroke. CLINICAL TRIAL REGISTRATION URL:
      http://www.clinicaltrials.gov. Unique identifier: NCT01186146.

PMID- 24097440
TI  - Does Social Support Buffer the Effect of Financial Strain on the Trajectory of
      Smoking in Older Japanese? A 19-Year Longitudinal Study.
AB  - OBJECTIVES: Although there is extensive research on the stress-buffering effects
      of social support on health, there is little understanding of this effect on
      health behaviors such as smoking, particularly during old age. This study aimed
      to estimate the effect of financial strain and the stress-buffering effect of
      social support, on the trajectory of smoking over an extended period of time
      among older Japanese. METHOD: Data came from a national sample of more than 4,800
      adults, aged 60 and older in Japan, with up to 7 repeated observations between
      1987 and 2006 (16,669 observations). Hierarchical linear modeling was used to
      analyze the intrapersonal and interpersonal differences in smoking. RESULTS:
      Higher financial strain at baseline was associated with greater amount of
      smoking, and a slower rate of decline, after adjusting for sociodemographic
      attributes. Greater instrumental support partially offset the deleterious effect
      of financial strain on the rate of decline in smoking. DISCUSSION: Our findings
      add a dynamic dimension to understanding the relationship among financial strain,
      social support, and smoking in old age. This knowledge is significant when
      designing health policies and interventions regarding health behaviors in late
      life.

PMID- 24097441
TI  - Pathways to late-life problematic gambling in seniors: a grounded theory
      approach.
AB  - PURPOSE OF THE STUDY: To develop a grounded theory on how older adults, who may
      not have previously experienced gambling issues, come to develop gambling
      problems in later life. DESIGN AND METHODS: Through semistructured in-depth
      interviews with 31 adults aged 56-85, routes that led the current sample of older
      adults to develop late-life gambling problems were identified and mapped into
      coherent pathways using a constructivist grounded theory methodology. RESULTS:
      Three main pathways to late-life problematic gambling were identified, all linked
      with a common theme of isolation: a grief pathway associated with unresolved
      losses; a habit pathway associated with habituation to gambling; and a dormant
      pathway marked by preexisting behavioral excess or impulsivity. Overall,
      unresolved losses and/or mismanagement of life's stresses were found to be the
      most significant predictors of late-life problematic gambling. IMPLICATIONS: As
      late-life problem gambling appears to predominantly signify late-life emotional
      distress and an attempt to deal with this distress using gambling as an escape,
      it is crucial for problem gambling prevention programs to raise awareness about
      the processes of loss and grief and provide ideas about constructive loss
      management. In addition, community-level recreational and social opportunities to
      combat isolation are identified.

PMID- 24097442
TI  - UV light-induced DNA lesions cause dissociation of yeast RNA polymerases-I and
      establishment of a specialized chromatin structure at rRNA genes.
AB  - The cytotoxicity of UV light-induced DNA lesions results from their interference
      with transcription and replication. DNA lesions arrest elongating RNA
      polymerases, an event that triggers transcription-coupled nucleotide excision
      repair. Since arrested RNA polymerases reduce the accessibility of repair factors
      to DNA lesions, they might be displaced. The fate of arrested RNA polymerases-II
      at DNA lesions has been extensively studied, yielding partially contradictory
      results. Considerably less is known about RNA polymerases-I that transcribe
      nucleosomes-depleted rRNA genes at very high rate. To investigate the fate of
      arrested RNA polymerases-I at DNA lesions, chromatin-immunoprecipitation,
      electron microscopy, transcription run-on, psoralen-cross-linking and chromatin
      endogenous cleavage were employed. We found that RNA polymerases-I density
      increased at the 5'-end of the gene, likely due to continued transcription
      initiation followed by elongation and pausing/release at the first DNA lesion.
      Most RNA polymerases-I dissociated downstream of the first DNA lesion,
      concomitant with chromatin closing that resulted from deposition of nucleosomes.
      Although nucleosomes were deposited, the high mobility group-box Hmo1 (component
      of actively transcribed rRNA genes) remained associated. After repair of DNA
      lesions, Hmo1 containing chromatin might help to restore transcription elongation
      and reopening of rRNA genes chromatin. 

PMID- 24097443
TI  - Handling the 3-methylcytosine lesion by six human DNA polymerases members of the
      B-, X- and Y-families.
AB  - Alkylating agents often generate 3-methylcytosine (3meC) lesions that are
      efficiently repaired by AlkB homologues. If AlkB homologue proteins are not
      functional, or the number of 3meC lesions exceeds the cellular repair capacity,
      the damage will persist in the genome and become substrate of DNA polymerases
      (Pols). Though alkylating agents are present in our environment and used in the
      clinics, currently nothing is known about the impact of 3meC on the accuracy and
      efficiency of human Pols. Here we compared the 3meC bypass properties of six
      human Pols belonging to the three families: B (Pol delta), X (Pols beta and
      lambda) and Y (Pols kappa, iota and eta). We show that under replicative
      conditions 3meC impairs B-family, blocks X-family, but not Y-family Pols, in
      particular Pols eta and iota. These Pols successfully synthesize opposite 3meC;
      Pol iota preferentially misincorporates dTTP and Pol eta dATP. The most efficient
      extenders from 3meC base-paired primers are Pols kappa and eta. Finally, using
      xeroderma pigmentosum variant patient cell extracts, we provide evidence that the
      presence of functional Pol eta is mandatory to efficiently overcome 3meC by
      mediating complete bypass or extension. Our data suggest that Pol eta is crucial
      for efficient 3meC bypass. 

PMID- 24097444
TI  - Human snRNA genes use polyadenylation factors to promote efficient transcription
      termination.
AB  - RNA polymerase II transcribes both protein coding and non-coding RNA genes and,
      in yeast, different mechanisms terminate transcription of the two gene types.
      Transcription termination of mRNA genes is intricately coupled to cleavage and
      polyadenylation, whereas transcription of small nucleolar (sno)/small nuclear
      (sn)RNA genes is terminated by the RNA-binding proteins Nrd1, Nab3 and Sen1. The
      existence of an Nrd1-like pathway in humans has not yet been demonstrated. Using
      the U1 and U2 genes as models, we show that human snRNA genes are more similar to
      mRNA genes than yeast snRNA genes with respect to termination. The Integrator
      complex substitutes for the mRNA cleavage and polyadenylation specificity factor
      complex to promote cleavage and couple snRNA 3'-end processing with termination.
      Moreover, members of the associated with Pta1 (APT) and cleavage factor I/II
      complexes function as transcription terminators for human snRNA genes with
      little, if any, role in snRNA 3'-end processing. The gene-specific factor,
      proximal sequence element-binding transcription factor (PTF), helps clear the U1
      and U2 genes of nucleosomes, which provides an easy passage for pol II, and the
      negative elongation factor facilitates termination at the end of the genes where
      nucleosome levels increase. Thus, human snRNA genes may use chromatin structure
      as an additional mechanism to promote efficient transcription termination in
      vivo. 

PMID- 24097557
TI  - Hyperglycemia impedes lung bacterial clearance in a murine model of cystic
      fibrosis-related diabetes.
AB  - Cystic fibrosis-related diabetes (CFRD) is the most common comorbidity associated
      with cystic fibrosis (CF), impacting more than half of patients over age 30. CFRD
      is clinically significant, portending accelerated decline in lung function, more
      frequent pulmonary exacerbations, and increased mortality. Despite the profound
      morbidity associated with CFRD, little is known about the underlying CFRD-related
      pulmonary pathology. Our aim was to develop a murine model of CFRD to explore the
      hypothesis that elevated glucose in CFRD is associated with reduced lung
      bacterial clearance. A diabetic phenotype was induced in gut-corrected CF
      transmembrane conductance regulator (CFTR) knockout mice (CFKO) and their CFTR
      expressing wild-type littermates (WT) utilizing streptozotocin. Mice were
      subsequently challenged with an intratracheal inoculation of Pseudomonas
      aeruginosa (PAO1) (75 MUl of 1-5 * 10(6) cfu/ml) for 18 h. Bronchoalveolar lavage
      fluid was collected for glucose concentration and cell counts. A portion of the
      lung was homogenized and cultured as a measure of the remaining viable PAO1
      inoculum. Diabetic mice had increased airway glucose compared with nondiabetic
      mice. The ability to clear bacteria from the lung was significantly reduced in
      diabetic WT mice and control CFKO mice. Critically, bacterial clearance by
      diabetic CFKO mice was significantly more diminished compared with nondiabetic
      CFKO mice, despite an even more robust recruitment of neutrophils to the airways.
      This finding that CFRD mice boast an exaggerated, but less effective,
      inflammatory cell response to intratracheal PAO1 challenge presents a novel and
      useful murine model to help identify therapeutic strategies that promote
      bacterial clearance in CFRD. 

PMID- 24097559
TI  - The collaboration of Antoine and Marie-Anne Lavoisier and the first measurements
      of human oxygen consumption.
AB  - Antoine Lavoisier (1743-1794) was one of the most eminent scientists of the late
      18th century. He is often referred to as the father of chemistry, in part because
      of his book Elementary Treatise on Chemistry. In addition he was a major figure
      in respiratory physiology, being the first person to recognize the true nature of
      oxygen, elucidating the similarities between respiration and combustion, and
      making the first measurements of human oxygen consumption under various
      conditions. Less well known are the contributions made by his wife, Marie-Anne
      Lavoisier. However, she was responsible for drawings of the experiments on oxygen
      consumption when the French revolution was imminent. These are of great interest
      because written descriptions are not available. Possible interpretations of the
      experiments are given here. In addition, her translations from English to French
      of papers by Priestley and others were critical in Lavoisier's demolition of the
      erroneous phlogiston theory. She also provided the engravings for her husband's
      textbook, thus documenting the extensive new equipment that he developed. In
      addition she undertook editorial work, for example in preparing his posthumous
      memoirs. The scientific collaboration of this husband-wife team is perhaps unique
      among the giants of respiratory physiology. 

PMID- 24097558
TI  - Estradiol activates epithelial sodium channels in rat alveolar cells through the
      G protein-coupled estrogen receptor.
AB  - Female sex predisposes individuals to poorer outcomes during respiratory
      disorders like cystic fibrosis and influenza-associated pneumonia. A common link
      between these disorders is dysregulation of alveolar fluid clearance via
      disruption of epithelial sodium channel (ENaC) activity. Recent evidence suggests
      that female sex hormones directly regulate expression and activity of alveolar
      ENaC. In our study, we identified the mechanism by which estradiol (E2) or
      progesterone (P4) independently regulates alveolar ENaC. Using cell-attached
      patch clamp, we measured ENaC single-channel activity in a rat alveolar cell line
      (L2) in response to overnight exposure to either E2 or P4. In contrast to P4, E2
      increased ENaC channel activity (NPo) through an increase in channel open
      probability (Po) and an increased number of patches with observable channel
      activity. Apical plasma membrane abundance of the ENaC alpha-subunit (alphaENaC)
      more than doubled in response to E2 as determined by cell surface biotinylation.
      alphaENaC membrane abundance was approximately threefold greater in lungs from
      female rats in proestrus, when serum E2 is greatest, compared with diestrus, when
      it is lowest. Our results also revealed a significant role for the G protein
      coupled estrogen receptor (Gper) to mediate E2's effects on ENaC. Overall, our
      results demonstrate that E2 signaling through Gper selectively activates alveolar
      ENaC through an effect on channel gating and channel density, the latter via
      greater trafficking of channels to the plasma membrane. The results presented
      herein implicate E2-mediated regulation of alveolar sodium channels in the sex
      differences observed in the pathogenesis of several pulmonary diseases. 

PMID- 24097560
TI  - Genetic deletion of IL-17A reduces cigarette smoke-induced inflammation and
      alveolar type II cell apoptosis.
AB  - Chronic obstructive pulmonary disease (COPD) is an inflammatory disorder marked
      by relative resistance to steroids. Inflammation and apoptosis have been
      suggested to be important mechanisms for COPD. Interleukin (IL)-17 superfamily
      has been associated with chronic inflammation and diminished responses to
      steroids. It is reasonable to consider that IL-17 may play a role in the
      pathogenesis of COPD. In this study, we examined IL-17 expression in mice exposed
      to cigarette smoke (CS) and investigated the contribution of IL-17 to CS-induced
      inflammation and alveolar cell apoptosis in IL-17(-/-) mice. After exposing wild
      type and IL-17(-/-) mice to mainstream CS for 4 wk, IL-17A, but not IL-17F,
      expression was increased in mice upon CS exposure. Neutrophil infiltration in the
      lungs of IL-17(-/-) mice was significantly decreased. In IL-17(-/-) mice, there
      is reduced expression of IL-6, macrophage inflammatory protein-2, and matrix
      metalloproteinase-12 compared with wild-type mice after CS exposure. The number
      of apoptotic type II alveolar cells was significantly increased in CS-exposed
      wild-type mice but not in IL-17(-/-) mice. The effect of IL-17A on type II
      alveolar cell apoptosis was confirmed in vitro through either addition of IL-17A
      or transient knockdown of IL-17A by small-interfering RNA transfection in type II
      alveolar cells. These findings suggest that IL-17A plays an important role in the
      inflammatory response to CS exposure through increased multiple inflammatory
      mediators. Moreover, IL-17 may also contribute to type II alveolar cell
      apoptosis. This study opens a new option in targeting IL-17A to modulate
      inflammatory response to CS and may be the bases for new therapy for COPD. 

PMID- 24097561
TI  - NF-kappaB pathway is involved in CRP-induced effects on pulmonary arterial
      endothelial cells in chronic thromboembolic pulmonary hypertension.
AB  - Chronic thromboembolic pulmonary hypertension (CTEPH) is characterized by
      thrombofibrotic obstruction of proximal pulmonary arteries. The cellular and
      molecular mechanisms underlying the pathogenesis remain incompletely understood,
      although we recently evidenced the potential involvement of the inflammatory
      marker C-reactive protein (CRP). We aimed to investigate the intracellular
      mechanisms induced by CRP in proximal pulmonary arterial endothelial cells
      (PAEC). PAEC were isolated from vascular material obtained during pulmonary
      endarterectomy. RNA was extracted from CRP-stimulated PAEC, and first-stand cDNA
      was generated. A RT(2) profiler PCR Array was used to evaluate the expression of
      84 key genes related to NF-kappaB-mediated signal transduction. CRP-induced NF
      kappaB activation was studied. The effects of pyrrolidine-dithio-carbamate
      ammonium (PDTC), an inhibitor of the NF-kappaB pathway, were investigated on CRP
      induced adhesion of monocytes to PAEC, adhesion molecule expression, endothelin-1
      (ET-1), interleukin-6 (IL-6), and von Willebrand factor (vWF) secretion. Compared
      with nonstimulated PAEC, serotonin receptor 2B was downregulated by 25%,
      inhibitor of NF-kappaB kinase subunit epsilon (IKBKE) by 30%, and toll-like
      receptor-4 and -6 by 18 and 39%, respectively, in CRP-stimulated PAEC. The
      transcription factor FOS was threefold upregulated. CRP induced RelA/NF-kappaBp65
      phosphorylation. PDTC dose dependently inhibited the adhesion of monocytes to CRP
      stimulated PAEC. PDTC also inhibited the CRP-induced expression of ICAM-1 at the
      surface of PAEC. PDTC impaired the secretion of ET-1 by 18% and tended to inhibit
      the secretion of IL-6 by CRP-stimulated PAEC by 46%. PDTC did not inhibit the CRP
      induced secretion of vWF. These results suggest an involvement of the NF-kappaB
      pathway in mediating different effects of CRP on proximal CTEPH-PAEC. 

PMID- 24097563
TI  - Flagellin/TLR5 signaling potentiates airway serous secretion from swine tracheal
      submucosal glands.
AB  - Airway serous secretion is essential for the maintenance of mucociliary transport
      in airway mucosa, which is responsible for the upregulation of mucosal immunity.
      Although there are many articles concerning the importance of Toll-like receptors
      (TLRs) in airway immune systems, the direct relationship between TLRs and airway
      serous secretion has not been well investigated. Here, we focused on whether TLR5
      ligand flagellin, which is one of the components of Pseudomonas aeruginosa, is
      involved in the upregulation of airway serous secretion. Freshly isolated swine
      tracheal submucosal gland cells were prepared, and the standard patch-clamp
      technique was applied for measurements of the whole cell ionic responses of these
      cells. Flagellin showed potentiating effects on these oscillatory currents
      induced by physiologically relevant low doses of acetylcholine (ACh) in a dose
      dependent manner. These potentiating effects were TLR5 dependent but TLR4
      independent. Both nitric oxide (NO) synthase inhibitors and cGMP-dependent
      protein kinase (cGK) inhibitors abolished these flagellin-induced potentiating
      effects. Furthermore, TLR5 was abundantly expressed on tracheal submucosal
      glands. Flagellin/TLR5 signaling further accelerated the intracellular NO
      synthesis induced by ACh. These findings suggest that TLR5 takes part in the
      airway mucosal defense systems as a unique endogenous potentiator of airway
      serous secretions and that NO/cGMP/cGK signaling is involved in this rapid
      potentiation by TLR5 signaling. 

PMID- 24097562
TI  - Metformin-stimulated AMPK-alpha1 promotes microvascular repair in acute lung
      injury.
AB  - Acute lung injury secondary to sepsis is a leading cause of mortality in sepsis
      related death. Present therapies are not effective in reversing endothelial cell
      dysfunction, which plays a key role in increased vascular permeability and
      compromised lung function. AMP-activated protein kinase (AMPK) is a molecular
      sensor important for detection and mediation of cellular adaptations to vascular
      disruptive stimuli. In this study, we sought to determine the role of AMPK in
      resolving increased endothelial permeability in the sepsis-injured lung. AMPK
      function was determined in vivo using a rat model of endotoxin-induced lung
      injury, ex vivo using the isolated lung, and in vitro using cultured rat
      pulmonary microvascular endothelial cells (PMVECs). AMPK stimulation using N1
      (alpha-d-ribofuranosyl)-5-aminoimidizole-4-carboxamide or metformin decreased the
      LPS-induced increase in permeability, as determined by filtration coefficient
      (Kf) measurements, and resolved edema as indicated by decreased wet-to-dry
      ratios. The role of AMPK in the endothelial response to LPS was determined by
      shRNA designed to decrease expression of the AMPK-alpha1 isoform in capillary
      endothelial cells. Permeability, wounding, and barrier resistance assays using
      PMVECs identified AMPK-alpha1 as the molecule responsible for the beneficial
      effects of AMPK in the lung. Our findings provide novel evidence for AMPK-alpha1
      as a vascular repair mechanism important in the pulmonary response to sepsis and
      identify a role for metformin treatment in the management of capillary injury. 

PMID- 24097630
TI  - Development of a coordinated allo T cell and auto B cell response against
      autosomal PTK2B after allogeneic hematopoietic stem cell transplantation.
AB  - It is well known that allo-reactive T cells play a crucial role in graft-versus
      leukemia and graft-versus-host disease after allogeneic hematopoietic stem cell
      transplantation (alloSCT). Allo-reactive CD4(+) T cells can mediate direct
      cytolysis, but may also stimulate production of IgG antibodies as helper cells.
      Immune complexes may subsequently be processed and presented by professional
      antigen presenting cells and stimulate induction of specific CD8(+) T cells. As
      such, proteins targeted in coordinated T- and B-cell responses may represent a
      class of immunodominant antigens in clinical responses after alloSCT. We
      previously identified LB-PTK2B-1T as HLA class II restricted polymorphic antigen
      in a patient treated with donor lymphocyte infusion for relapsed chronic myeloid
      leukemia after HLA-matched alloSCT. Since PTK2B has also been described as
      antibody target, we here investigated whether a coordinated T- and B-cell
      response against PTK2B was induced. Patient serum before and after alloSCT and
      donor lymphocyte infusion (DLI) was screened for antibodies, and we indeed
      observed development of a humoral immune response against PTK2B. Antibodies
      against PTK2B were only found after DLI and, in contrast to the CD4(+) T cells,
      recognized a monomorphic region of the protein. To our knowledge, this is the
      first description of a coordinated allo-reactive CD4(+) T-cell and auto-reactive
      antibody response against an autosomal antigen. 

PMID- 24097632
TI  - Osteoclasts are not crucial for hematopoietic stem cell maintenance in adult
      mice.
AB  - The osteoclast is vital for establishment of normal hematopoiesis in the
      developing animal. However, its role for maintenance of hematopoiesis in
      adulthood is more controversial. To shed more light on this process, we
      transplanted hematopoietic stem cells from two osteopetrotic mouse models, with
      lack of osteoclasts or defective osteoclast function, to normal adult mice and
      examined the bone phenotype and hematopoiesis in the recipients. B6SJL mice were
      lethally irradiated and subsequently transplanted with oc/oc, Receptor Activator
      of Nuclear Factor Kappa B knockout or control fetal liver cells. Osteoclasts
      derived from the recipient animals were tested in vitro for osteoclastogenesis
      and resorptive function. Bone remodeling changes were assessed using biomarkers
      of bone turnover and micro-CT. Hematopoiesis was assessed by flow cytometry and
      colony formation, and hematopoietic stem cell function by secondary competitive
      transplantations and cell cycle analysis. After transplantation, a donor
      chimerism of 97-98% was obtained, and by 15 weeks mild osteopetrosis had
      developed in recipients of cells from osteopetrotic mice. There were no
      alterations in the number of bone marrow cells. Colony formation was slightly
      reduced in Receptor Activator of Nuclear Factor Kappa B knockout recipients but
      unchanged in oc/oc recipients. Phenotypically, stem cells were marginally reduced
      in recipients of cells from osteopetrotic mice, but no significant difference was
      seen in cell cycle status and in competitive secondary transplantations all three
      groups performed equally well. Our results indicate that osteoclast function is
      not crucial for hematopoietic stem cell maintenance in adult mice. 

PMID- 24097631
TI  - Intensive induction is effective in selected octogenarian acute myeloid leukemia
      patients: prognostic significance of karyotype and selected molecular markers
      used in the European LeukemiaNet classification.
AB  - We investigated whether octogenarian patients with acute myeloid leukemia
      enrolled onto Cooperative Group clinical trials and treated with intensive
      induction therapy could be cured, and whether karyotype and selected molecular
      markers had any prognostic significance in these patients. Among 138 patients
      with cytogenetic information, normal karyotype was the most common (47.1%)
      followed by complex karyotype (14.5%) and sole +8 (9.4%). Among these patients,
      the relapse-free survival rate at 1 year was 37% and 13% at 3 years, and the
      respective overall survival rates were 24% and 8%. Whereas the 90 patients who
      survived beyond 30 days had the same relapse-free survival rates, their 1-year
      and 3-year overall survival rates were 36% and 11%, respectively. Of the 66
      patients surviving beyond 30 days who could be classified into European
      LeukemiaNet genetic groups, those in the intermediate-I group had better overall
      survival than patients in the adverse group (P=0.01). Among patients with
      cytogenetically normal acute myeloid leukemia who were tested for the European
      LeukemiaNet-associated molecular alterations, FLT3-internal tandem duplication
      and NPM1 mutations, it was found that FLT3-internal tandem duplication (detected
      in 29% of patients) did not associate with overall survival (P=0.31), whereas
      NPM1 mutations (30%) were associated with a significantly longer overall survival
      (P=0.002). We conclude that intensive induction is effective and indicated in
      selected octogenarians with acute myeloid leukemia, that their overall survival
      varies among the European LeukemiaNet genetic groups and that NPM1 mutations may
      be of prognostic significance among octogenarian patients with cytogenetically
      normal acute myeloid leukemia. 

PMID- 24097633
TI  - Umbilical cord blood transplantation from unrelated donors in patients with
      Philadelphia chromosome-positive acute lymphoblastic leukemia.
AB  - There are very few disease-specific studies focusing on outcomes of umbilical
      cord blood transplantation for Philadelphia chromosome-positive acute
      lymphoblastic leukemia. We report the outcome of 45 patients with Philadelphia
      chromosome-positive acute lymphoblastic leukemia who underwent myeloablative
      single unit cord blood transplantation from unrelated donors within the
      GETH/GITMO cooperative group. Conditioning regimens were based on combinations of
      thiotepa, busulfan, cyclophospamide or fludarabine, and antithymocyte globulin.
      At the time of transplantation, 35 patients (78%) were in first complete
      remission, four (8%) in second complete remission and six (14%) in third or
      subsequent response. The cumulative incidence of myeloid engraftment was 96% at a
      median time of 20 days and significantly better for patients receiving higher
      doses of CD34(+) cells. The incidence of acute grade II-IV graft-versus-host
      disease was 31%, while that of overall chronic graft-versus-host disease was 53%.
      Treatment-related mortality was 17% at day +100 and 31% at 5 years. The 5-year
      relapse, event-free survival and overall survival rates were 31%, 36% and 44%,
      respectively. Although the event-free and overall survival rates in patients
      without BCR/ABL transcripts detectable at time of transplant were better than
      those in whom BCR/ABL transcripts were detected (46% versus 24% and 60% versus
      30%, respectively) these differences were not statistically significant in the
      univariate analysis (P=0.07). These results demonstrate that umbilical cord blood
      transplantation from unrelated donors can be a curative treatment for a
      substantial number of patients with Philadelphia chromosome-positive acute
      lymphoblastic leukemia. 

PMID- 24097666
TI  - The adaptive endoplasmic reticulum stress response to lipotoxicity in progressive
      human nonalcoholic fatty liver disease.
AB  - Nonalcoholic fatty liver disease (NAFLD) may progress from simple steatosis to
      severe, nonalcoholic steatohepatitis (NASH) in 7%-14% of the U.S. population
      through a second "hit" in the form of increased oxidative stress and
      inflammation. Endoplasmic reticulum (ER) stress signaling and the unfolded
      protein response (UPR) are triggered when high levels of lipids and misfolded
      proteins alter ER homeostasis creating a lipotoxic environment within NAFLD
      livers. The objective of this study was to determine the coordinate regulation of
      ER stress-associated genes in the progressive stages of human NAFLD. Human liver
      samples categorized as normal, steatosis, NASH (Fatty), and NASH (Not Fatty) were
      analyzed by individual Affymetrix GeneChip Human 1.0 ST microarrays, immunoblots,
      and immunohistochemistry. A gene set enrichment analysis was performed on
      autophagy, apoptosis, lipogenesis, and ER stress/UPR gene categories. An
      enrichment of downregulated genes in the ER stress-associated lipogenesis and ER
      stress/UPR gene categories was observed in NASH. Conversely, an enrichment of
      upregulated ER stress-associated genes for autophagy and apoptosis gene
      categories was observed in NASH. Protein expression of the adaptive liver
      response protein STC2 and the transcription factor X-box binding protein 1
      spliced (XBP-1s) were significantly elevated among NASH samples, whereas other
      downstream ER stress proteins including CHOP, ATF4, and phosphorylated JNK and
      eIF2alpha were not significantly changed in disease progression. Increased
      nuclear accumulation of total XBP-1 protein was observed in steatosis and NASH
      livers. The findings reveal the presence of a coordinated, adaptive
      transcriptional response to hepatic ER stress in human NAFLD. 

PMID- 24097667
TI  - Characterization of intracellular inclusions in the urothelium of mice exposed to
      inorganic arsenic.
AB  - Inorganic arsenic (iAs) is a known human carcinogen at high exposures, increasing
      the incidences of urinary bladder, skin, and lung cancers. In most mammalian
      species, ingested iAs is excreted mainly through urine primarily as
      dimethylarsinic acid (DMA(V)). In wild-type (WT) mice, iAs, DMA(V), and
      dimethylarsinous acid (DMA(III)) exposures induce formation of intramitochondrial
      urothelial inclusions. Arsenite (iAs(III)) also induced intranuclear inclusions
      in arsenic (+3 oxidation state) methyltransferase knockout (As3mt KO) mice. The
      arsenic-induced formation of inclusions in the mouse urothelium was dose and time
      dependent. The inclusions do not occur in iAs-treated rats and do not appear to
      be related to arsenic-induced urothelial cytotoxicity. Similar inclusions in
      exfoliated urothelial cells from humans exposed to iAs have been incorrectly
      identified as micronuclei. We have characterized the urothelial inclusions using
      transmission electron microscopy (TEM), DNA-specific 4',6-diamidino-2
      phenylindole (DAPI), and non-DNA-specific Giemsa staining and determined the
      arsenical content. The mouse inclusions stained with Giemsa but not with the DAPI
      stain. Analysis of urothelial mitochondrial- and nuclear-enriched fractions
      isolated from WT (C57BL/6) and As3mt KO mice exposed to arsenate (iAs(V)) for 4
      weeks showed higher levels of iAs(V) in the treated groups. iAs(III) was the
      major arsenical present in the enriched nuclear fraction from iAs(V)-treated
      As3mt KO mice. In conclusion, the urothelial cell inclusions induced by
      arsenicals appear to serve as a detoxifying sequestration mechanism similar to
      other metals, and they do not represent micronuclei. 

PMID- 24097668
TI  - Molecular mechanisms of hepatocellular apoptosis induced by trovafloxacin-tumor
      necrosis factor-alpha interaction.
AB  - Idiosyncratic drug-induced liver injury (IDILI) continues to be a significant
      human health problem. IDILI is characterized as occurring in a minority of
      individuals exposed to a drug, yet it accounts for as much as 17% of all cases of
      acute liver failure. Despite these concerns, the mechanisms underlying IDILI
      remain unknown. Trovafloxacin (TVX), which causes IDILI in humans, also causes
      hepatocellular death in vitro when combined with tumor necrosis factor-alpha
      (TNF) treatment. However, the molecular mechanisms involved in this toxicity are
      not fully characterized. The purpose of this study was to identify mechanisms by
      which TVX and TNF interact to cause hepatocellular death, with a focus on a human
      hepatocyte cell line. TVX and TNF interacted to cause cytotoxicity in HepG2 cells
      at drug concentrations similar to those in people undergoing TVX therapy. TVX/TNF
      treatment caused apoptosis and DNA damage in HepG2 cells that depended on caspase
      activation. Prolonged activation of JNK occurred in TVX/TNF-induced cytotoxicity,
      and treatment with the JNK selective inhibitor SP600125 attenuated cytotoxicity.
      TVX/TNF cotreatment also caused cytotoxicity in isolated primary murine
      hepatocytes that was dependent on caspase activation. These results increase
      understanding of molecular signaling pathways involved in hepatocellular death
      caused by a drug with idiosyncratic liability in the presence of TNF. 

PMID- 24097669
TI  - Pulmonary toxicity of perfluorinated silane-based nanofilm spray products:
      solvent dependency.
AB  - A number of cases of pulmonary injury by use of aerosolized surface coating
      products have been reported worldwide. The aerosol from a commercial alcohol
      based nanofilm product (NFP) for coating of nonabsorbing surfaces was found to
      induce severe lung damage in a recent mouse bioassay. The NFP contained a
      1H,1H,2H,2H-perfluorooctyl trialkoxysilane (POTS) and the effects were associated
      with the hydrolyzed forms of the silane; increase in hydrolyzation resulted in
      faster induction of compromised breathing and induction of lung damage. In this
      study, the impact of the solvent on the toxicity of POTS has been investigated.
      BALB/cA mice were exposed to aerosolized water-based NFPs containing POTS, and
      solutions of hydrolyzed POTS in methanol, ethanol, and 2-propanol, respectively.
      No acute respiratory effect was observed at exposure concentrations up to 110
      mg/m3 with an aqueous solution of POTS. However, exposure to POTS in methanol
      resulted in a decrease of the tidal volume--an effect that did not resolve within
      the recovery period. After 27 min of exposure, the tidal volume had decreased by
      25%, indicating partial alveolar collapse. For POTS in ethanol and 2-propanol, a
      25% reduction of the tidal volume was observed after 13 and 9 min, respectively;
      thus, the tidal volume was affected by increase of the chain length. This was
      confirmed in vitro by investigating lung surfactant function after addition of
      POTS in different solvents. The addition of vaporized methanol, 2-propanol, or
      acetone to aerosolized POTS in methanol further exacerbated the tidal volume
      reduction, demonstrating that the concentration of vaporized solvent participated
      in the toxicity of POTS.

PMID- 24097670
TI  - Hepatic clearance of 6 polycyclic aromatic hydrocarbons by isolated perfused
      trout livers: prediction from in vitro clearance by liver S9 fractions.
AB  - Isolated perfused trout livers were used to evaluate in vitro-in vivo metabolism
      extrapolation procedures for fish. In vitro depletion rates for 6 polycyclic
      aromatic hydrocarbons (PAHs) were measured using liver S9 fractions and
      extrapolated to the intact tissue. Predicted hepatic clearance (CLH) values were
      then compared with values exhibited by intact livers. Binding in liver perfusates
      was manipulated using bovine serum albumin (BSA) and was characterized by solid
      phase microextraction. Additional studies were conducted to develop binding terms
      (f U; calculated as the ratio of unbound fractions in liver perfusate [f U,PERF]
      and the S9 system [f U,S9]) used as inputs to a well-stirred liver model. Hepatic
      clearance values for pyrene and benzo[a]pyrene, predicted by extrapolating in
      vitro data to the intact tissue, were in good agreement with measured values (< 2
      fold difference). This can be partly attributed to the rapid rate at which both
      compounds were metabolized by S9 fractions, resulting in perfusion-limited
      clearance. Predicted levels of CLH for the other PAHs underestimated observed
      values although these differences were generally small (< 3-fold, except for
      naphthalene). Setting f U = 1.0 improved clearance predictions at the highest
      tested BSA concentration (10mg/ml), suggesting that trout S9 fractions exhibit
      lower levels of intrinsic activity than the intact tissue or that the full
      binding assumption (ie, f U = f U,PERF/f U,S9) underestimates the availability of
      hydrophobic substrates to hepatic metabolizing enzymes. These findings provide
      qualified support for procedures currently being used to predict metabolism
      impacts on chemical accumulation by fish based on measured rates of in vitro
      activity. 

PMID- 24097795
TI  - Development and content validation of the Pediatric Eating Assessment Tool (Pedi
      EAT).
AB  - PURPOSE: In this article, the authors describe the development and content
      validation of a parent-report measure of problematic eating behaviors: the
      Pediatric Eating Assessment Tool (Pedi-EAT). METHOD: In Phase I, items were
      generated from parents' descriptions of problematic feeding behaviors of
      children, review of literature, and review of existing eating-related
      instruments. In Phase II, interdisciplinary experts on pediatric eating behaviors
      rated the items for clarity and relevance using content validity indices (CVI)
      and provided feedback on the comprehensiveness of the instrument. In Phases III
      and IV, 2 groups of parents of children with and without feeding difficulties
      participated in cognitive interviews to gain respondent feedback on content,
      format, and item interpretation. The authors analyzed interviews using matrix
      display strategies. RESULTS: Experts rated the total scale CVI > .90 for both
      relevance and clarity; item CVI ranged from .67 to 1.0 for relevance and .5 to
      1.0 for clarity. Analysis of each item with low scores, along with experts' and
      parents' feedback, resulted in refinement of the items, scoring options, and
      directions. Experts and parents added additional items. Readability after
      refinements was acceptable at less than a 5th-grade level. CONCLUSION: The Pedi
      EAT was systematically developed and content validated with input from
      researchers, clinicians, and parents.

PMID- 24097794
TI  - The cost of injury and trauma care in low- and middle-income countries: a review
      of economic evidence.
AB  - INTRODUCTION: Injuries are a significant cause of mortality and morbidity, of
      which more than 90% occur in low- and middle-income countries (LMICs). Given the
      extent of this burden being confronted by LMICs, there is need to place injury
      prevention at the forefront of public health initiatives and to understand the
      costs associated with injury. The aim of this article is to describe the extent
      to which injury-related costing studies have been conducted in LMICs. METHODS: A
      review of literature was performed to explore costing data available for injury
      and/or trauma care in LMICs. Study quality was described using recommendations
      from the Community Guide's quality assessment tool for economic evaluations.
      RESULTS: The review identified 68 studies, of which 13 were full economic
      evaluations. Cost of injury varied widely with mean costs ranging from US$14 to
      US$17 400. In terms of injury-prevention interventions, cost per disability
      adjusted life year averted for injury-prevention interventions ranged from
      US$10.90 for speed bump installation to US$17 000 for drunk driving and breath
      testing campaigns in Africa. The studies varied in quality, ranging from very
      good to unsatisfactory. DISCUSSION: There is a lack of injury-related economic
      evidence from LMICs. Current costing research has considerable variability in the
      costs and cost descriptions of injury and associated prevention interventions.
      The generalizability of these studies is limited. Yet the economic burden of
      injury is high, suggesting significant potential for cost savings through injury
      prevention. A standardized approach to economic evaluation of injury in LMICs is
      needed to further prioritize investing in injury prevention.

PMID- 24097796
TI  - Volumes of discrete sips from straws of varying internal diameters.
AB  - PURPOSE: In this study, the authors examined mean volumes of discrete sips
      performed by healthy adults from straws varying in internal diameter. METHOD:
      Forty healthy adults sipped water from each of 7 straws varying in internal
      diameter (0.65-5.00 mm). Bolus volumes associated with 3 discrete sips were
      recorded under each sip condition. RESULTS: Straw diameter had a significant
      effect on bolus size, with the smallest diameter straws eliciting the smallest
      bolus volumes. Bolus volumes did not vary according to age or sex. Considerable
      intersubject variation was observed, particularly for the straws with the largest
      diameters. Intrasubject variability across 3 trials was minimal. CONCLUSIONS: The
      findings support the hypothesis that narrower straw diameters are associated with
      smaller bolus volumes in healthy adults. Additional study is needed to determine
      whether individuals with dysphagia demonstrate similar patterns of bolus size
      associated with straws varying in internal diameter and whether such variations
      have clinical benefit.

PMID- 24097798
TI  - Rare transformation in repeat renal biopsies suggests a different pathogenesis of
      segmental and global lesions in proliferative lupus nephritis.

PMID- 24097797
TI  - Increased ERK signalling promotes inflammatory signalling in primary airway
      epithelial cells expressing Z alpha1-antitrypsin.
AB  - Overexpression of Z alpha1-antitrypsin is known to induce polymer formation,
      prime the cells for endoplasmic reticulum stress and initiate nuclear factor
      kappa B (NF-kappaB) signalling. However, whether endogenous expression in primary
      bronchial epithelial cells has similar consequences remains unclear. Moreover,
      the mechanism of NF-kappaB activation has not yet been elucidated. Here, we
      report excessive NF-kappaB signalling in resting primary bronchial epithelial
      cells from ZZ patients compared with wild-type (MM) controls, and this appears to
      be mediated by mitogen-activated protein/extracellular signal-regulated kinase,
      EGF receptor and ADAM17 activity. Moreover, we show that rather than being a
      response to protein polymers, NF-kappaB signalling in airway-derived cells
      represents a loss of anti-inflammatory signalling by M alpha1-antitrypsin.
      Treatment of ZZ primary bronchial epithelial cells with purified plasma M alpha1
      antitrypsin attenuates this inflammatory response, opening up new therapeutic
      options to modulate airway inflammation in the lung. 

PMID- 24097800
TI  - Aortic valve calcification in chronic kidney disease.
AB  - Several clinical studies reported an increased prevalence and accelerated
      progression of aortic valve calcification among patients with end-stage renal
      disease when compared with subjects with normal kidney function. Recently,
      mechanisms of calcific valve degeneration have been further elucidated and many
      of the pathways involved could be amplified in patients with decreased renal
      function. In particular, calcium-phosphate balance, MGP metabolism,
      OPG/RANK/RANKL triad, fetuin-A mineral complexes and FGF-23/Klotho axis have been
      shown to be impaired among patients with advanced chronic kidney disease and
      could play a role during vascular/valve calcification. The scope of the present
      review is to summarize the clinical data and the pathophysiological mechanisms
      potentially involved in the link between renal function decline and the
      progression of aortic valve disease. 

PMID- 24097799
TI  - Renal vein cytokine release as an index of renal parenchymal inflammation in
      chronic experimental renal artery stenosis.
AB  - BACKGROUND: Renal parenchymal inflammation is a critical determinant of kidney
      injury in renal artery stenosis (RAS) but is difficult to assess in the single
      kidney without tissue samples. Whether renal vein (RV) levels of inflammatory
      markers reflect active parenchymal inflammation remains unknown. We evaluated the
      relationship between net RV cytokine release and tissue inflammation in the post
      stenotic kidney. METHODS: Pigs were studied after 10 weeks of RAS treated 4 weeks
      earlier with intra-renal vehicle or anti-inflammatory mesenchymal stem cells
      (MSCs) or normal control. Single-kidney renal blood flow was measured by fast
      computerized tomography. RV and inferior vena cava levels of tumor necrosis
      factor (TNF)-alpha, interferon (IF)-gamma, monocyte chemoattractant protein (MCP
      1) and interleukin (IL)-10 were measured by enzyme-linked immunosorbent assay,
      and their net release calculated. Renal expression of the same cytokines was
      correlated with their net release. RESULTS: Net release of TNF-alpha, IF-gamma
      and MCP-1 was higher in RAS compared with normal and to the contralateral kidney
      (all P<0.05), decreased in MSC-treated pigs as was their tissue expression.
      Contrarily, the release of the anti-inflammatory IL-10 was lower in RAS and
      normalized in RAS+MSC. The net release of TNF-alpha, MCP-1 and IL-10 directly
      correlated with their tissue expression. The ratio of inflammatory-to-reparative
      macrophages directly correlated with the release of MCP-1, but inversely with the
      release of IL-10. In vitro cultured MSCs also induced a shift in the macrophage
      phenotype from inflammatory (M1) to reparative (M2). CONCLUSIONS: Our findings
      demonstrate that the release of inflammatory markers from the affected kidney
      provides an index of renal tissue inflammation in experimental RAS.

PMID- 24097801
TI  - Determination of uromodulin in human urine: influence of storage and processing.
AB  - BACKGROUND: Uromodulin (Tamm-Horsfall protein) is the most abundant protein
      excreted in the urine under physiological conditions. It is exclusively produced
      in the kidney and secreted into the urine via proteolytic cleavage. The
      involvement of UMOD, the gene that encodes uromodulin, in rare autosomal dominant
      diseases, and its robust genome-wide association with the risk of chronic kidney
      disease suggest that the level of uromodulin in urine could represent a critical
      biomarker for kidney function. The structure of uromodulin is complex, with
      multiple disulfide bonds and typical domains of extracellular proteins. METHODS:
      Thus far, the conditions influencing stability and measurement of uromodulin in
      human urine have not been systematically investigated, giving inconsistent
      results. In this study, we used a robust, in-house ELISA to characterize the
      conditions of sampling and storage necessary to provide a faithful dosage of
      uromodulin in the urine. RESULTS: The levels of uromodulin in human urine were
      significantly affected by centrifugation and vortexing, as well as by the
      conditions and duration of storage. CONCLUSIONS: These results validate a simple,
      low-cost ELISA and document the optimal conditions of processing and storage for
      measuring uromodulin in human urine.

PMID- 24097802
TI  - Quality and consistency of clinical practice guidelines for the management of
      children on chronic dialysis.
AB  - BACKGROUND: Clinical practice guidelines aim to improve the quality of care, yet
      for users of guidelines it is often not clear how these guidelines were developed
      and whether the recommendations are robust. We aimed to identify all current
      published guidelines for the management of children on chronic dialysis, assess
      the quality of their development and evaluate consistency among their
      recommendations. METHODS: We searched Medline (1948 to January 2012), and
      relevant websites of guideline development programmes. Three reviewers appraised
      all 17 identified guidelines with the Appraisal of Guidelines for Research and
      Evaluation (AGREE) II instrument. RESULTS: The guidelines were developed by five
      different professional associations. The overall mean AGREE II score from seven
      Kidney Disease Outcomes Quality Initiatives (KDOQI) guidelines was considered
      sufficient (mean scores 64-75%), and from all other 10 guidelines poor (29-44%).
      Five out of seven KDOQI guidelines scored weak on applicability. We found
      important inconsistencies between recommendations concerning initiation of renal
      replacement therapy, management of haemoglobin level and the use of mupirocin to
      prevent exit-site infections. CONCLUSIONS: While the recently developed KDOQI
      guidelines meet the modern quality standards, advice for implementation of these
      recommendations is lacking. There is an urgent need for international
      collaboration and coordination to ensure that the management of children on
      chronic dialysis is informed by relevant and high-quality evidence.

PMID- 24097803
TI  - The concept of substance use disorders. A commentary on 'Defining substance use
      disorders: do we really need more than heavy use' by Rehm et al.
AB  - Substance use disorders reflect more than just substance use. At one level they
      are patterns of behaviour, at another level they are clusters of experiences and
      physiological features. Substance use disorders are strongly correlated with the
      level of substance use, but the importance of defining them as disorders is
      because this determines the need for treatment (including detoxification, agonist
      maintenance treatment and other pharmacotherapies). The severity of a substance
      disorder also strongly influences the individual's prognosis. Quantification of
      substance use is valuable for both clinical and epidemiological purposes, but it
      should be as precise as possible and notions such as "heavy use over time" are
      not fit for purpose. 

PMID- 24097804
TI  - Blood and lymphatic vasculature in the ovary: development, function and disease.
AB  - BACKGROUND: The remodelling of the blood vasculature has been the subject of much
      research while rapid progress in the understanding of the factors controlling
      lymphangiogenesis in the ovary has only been reported more recently. The ovary
      undergoes cyclic remodelling throughout each menstrual/estrous cycle. This
      process requires significant vascular remodelling to supply each new cohort of
      growing follicles. METHODS: Literature searches were performed to review studies
      on the ovarian lymphatic vasculature that described spatial, temporal and
      functional data in human or animal species. The role of ovarian blood and
      lymphatic vasculature in the pathogenesis of ovarian disease and dysfunction was
      also explored. RESULTS: Research in a number of species including zebrafish,
      rodents and primates has described the lymphatic vasculature within the
      remodelling ovary, while recent research in mouse has confirmed hormonal
      regulation of lymphangiogenic growth factors, their receptors and also a role for
      the protease, ADAMTS1 in the development of the lymphatic vasculature. With a
      critical role in the maintenence of fluid homeostasis, the ovarian lymphatic
      vasculature is important for normal ovarian function and has been linked to
      syndromes involving ovarian fluid imbalance, including ovarian hyperstimulation
      syndrome and massive ovarian edema. The lymphatic vasculature has also been
      heavily implicated in the metastatic cancer process. CONCLUSION: The spatial and
      temporal regulation of the ovarian lymphatic vasculature has now been reported in
      a number of species and the data also implicate the ovarian lymphatic vasculature
      in ovarian pathologies, including cancer and those linked with use of artificial
      reproduction technologies.

PMID- 24097805
TI  - Short report: premastication in rural Gabon--a cross-sectional survey.
AB  - Premastication-defined as pre-chewing of food for infants by their caregiver-is a
      common feeding practice in various societies. To date the impact of
      premastication on children's health including the potential for transmission of
      infectious diseases is not well understood. Since there are no epidemiologic data
      on premastication from resource poor regions in Central Africa, we investigated
      the epidemiology and demographic variables associated with premastication in
      Central Africa. Between 2011 and 2012, mothers were interviewed about child
      feeding behaviors in three rural communities in Gabon. A quarter (n = 20, 24%) of
      82 participants stated to perform premastication regularly. Despite the small
      sample size, our study provides first baseline data for the epidemiology of
      premastication in Central Africa, indicating that this feeding practice is common
      in rural communities. 

PMID- 24097806
TI  - Susceptibility of tick cell lines to infection with Alkhumra haemorrhagic fever
      virus.
AB  - BACKGROUND: Although Alkhumra haemorrhagic fever virus (AHFV) has been isolated
      from ticks, epidemiological data suggest that it is transmitted from livestock to
      humans by direct contact with animals or by mosquito bites, but not by ticks.
      This study was carried out to assess the ability of the virus to replicate in
      tick cells in vitro. METHODS: AHFV was inoculated into cell lines derived from
      the hard ticks Hyalomma anatolicum (HAE/CTVM9) and Rhipicephalus appendiculatus
      (RAE/CTVM1) and the soft tick Ornithodoros moubata (OME/CTVM24). Inoculated cells
      were directly examined every week for 4 weeks by real-time reverse transcription
      PCR and by IFAT using polyclonal antibodies. RESULTS: AHFV RNA was detected in
      all three inoculated tick cell lines throughout the 4-week observation period at
      levels up to almost twice that of the inoculum, but none of them exhibited a
      cytopathic effect. AHFV antigen could be detected in all three cell lines by
      IFAT. Titration of tick cell culture suspension in LLC-MK2 cells yielded AHFV
      titres of 10(6.6) 50% tissue culture infective dose (TCID50)/ml for OME/CTVM24
      and 10(5.5) TCID50/ml for RAE/CTVM1 cells after 4 weeks of culturing; no viable
      virus was detected in HAE/CTVM9 cells. CONCLUSION: This is the first description
      of propagation of AHFV in tick cells.

PMID- 24097807
TI  - Using electronic health record data to develop inpatient mortality predictive
      model: Acute Laboratory Risk of Mortality Score (ALaRMS).
AB  - OBJECTIVE: Using numeric laboratory data and administrative data from hospital
      electronic health record (EHR) systems, to develop an inpatient mortality
      predictive model. METHODS: Using EHR data of 1,428,824 adult discharges from 70
      hospitals in 2006-2007, we developed the Acute Laboratory Risk of Mortality Score
      (ALaRMS) using age, gender, and initial laboratory values on admission as
      candidate variables. We then added administrative variables using the Agency for
      Healthcare Research and Quality (AHRQ)'s clinical classification software (CCS)
      and comorbidity software (CS) as disease classification tools. We validated the
      model using 770,523 discharges in 2008. RESULTS: Mortality predictors with ORs
      >2.00 included age, deranged albumin, arterial pH, bands, blood urea nitrogen,
      oxygen partial pressure, platelets, pro-brain natriuretic peptide, troponin I,
      and white blood cell counts. The ALaRMS model c-statistic was 0.87. Adding the
      CCS and CS variables increased the c-statistic to 0.91. The relative
      contributions were 69% (ALaRMS), 25% (CCS), and 6% (CS). Furthermore, the
      integrated discrimination improvement statistic demonstrated a 127% (95% CI 122%
      to 133%) overall improvement when ALaRMS was added to CCS and CS variables. In
      contrast, only a 22% (CI 19% to 25%) improvement was seen when CCS and CS
      variables were added to ALaRMS. CONCLUSIONS: EHR data can generate clinically
      plausible mortality predictive models with excellent discrimination. ALaRMS uses
      automated laboratory data widely available on admission, providing opportunities
      to aid real-time decision support. Models that incorporate laboratory and AHRQ's
      CCS and CS variables have utility for risk adjustment in retrospective outcome
      studies.

PMID- 24097808
TI  - Delayed diagnosis of phenylketonuria - a case report of two siblings.
AB  - Phenylketonuria (PKU), is an autosomal recessive condition affecting the amino
      acid metabolism. The UK National newborn screening programme was commenced in
      1969 and PKU is one among the five conditions included in the screening
      programme. We present the case history of two siblings of a family with a delayed
      diagnosis of PKU. This case history highlights such an occurrence. PKU should be
      considered as an important differential in the diagnosis of adult patients with
      learning difficulties, seizures and behavioural problems. It would be prudent to
      instigate plasma and urine amino/organic acid analyses in adult patients with
      unexplained neuropsychological manifestations. 

PMID- 24097809
TI  - A review of pancreatic cyst fluid analysis in the differential diagnosis of
      pancreatic cyst lesions.
AB  - Diagnosis and management of pancreatic cyst lesions is challenging as there is
      currently no investigation that offers both high diagnostic sensitivity and high
      specificity for the identification of potentially malignant lesions. Accurate
      classification of these lesions is vital in order to avoid unnecessary treatment
      of benign lesions and missed opportunities for early treatment of lesions that
      are malignant/pre-malignant. Pancreatic cyst fluid analysis has an important role
      in diagnosis, although all currently available investigations based on fluid
      analysis have significant limitations. Cytological analysis can reveal features
      that are specific for a certain class of cyst, but offers limited sensitivity in
      detecting malignant/pre-malignant cysts. Measurement of tumour markers,
      particularly carcinoembryonic antigen can also be informative. Concentrations of
      cyst fluid carcinoembryonic antigen tend to be higher in malignant/pre-malignant
      cysts, although there is a wide overlap between the various classes of cyst. A
      number of studies have suggested that diagnostic carcinoembryonic antigen cut
      offs can be chosen that provide a high degree of specificity but limited
      sensitivity. Studies of the analytical validity of tumour marker assays in
      pancreatic cyst fluid analysis have highlighted discrepancies in some fluid
      specimens, which require further investigation. DNA analysis also has a role. In
      particular, K-Ras-2 mutational analysis appears to provide high specificity for
      detection of malignant/pre-malignant lesions. A number of diagnostic algorithms
      have been published, integrating use of available investigations in order to
      achieve the optimum discrimination of benign and potentially malignant cysts.
      Research into new biochemical markers and optimal use of available pancreatic
      cyst fluid analyses is ongoing. 

PMID- 24097810
TI  - Neurovascular decoupling is associated with severity of cerebral amyloid
      angiopathy.
AB  - OBJECTIVES: We used functional MRI (fMRI), transcranial Doppler ultrasound, and
      visual evoked potentials (VEPs) to determine the nature of blood flow responses
      to functional brain activity and carbon dioxide (CO2) inhalation in patients with
      cerebral amyloid angiopathy (CAA), and their association with markers of CAA
      severity. METHODS: In a cross-sectional prospective cohort study, fMRI,
      transcranial Doppler ultrasound CO2 reactivity, and VEP data were compared
      between 18 patients with probable CAA (by Boston criteria) and 18 healthy
      controls, matched by sex and age. Functional MRI consisted of a visual task
      (viewing an alternating checkerboard pattern) and a motor task (tapping the
      fingers of the dominant hand). RESULTS: Patients with CAA had lower amplitude of
      the fMRI response in visual cortex compared with controls (p = 0.01), but not in
      motor cortex (p = 0.22). In patients with CAA, lower visual cortex fMRI amplitude
      correlated with higher white matter lesion volume (r = -0.66, p = 0.003) and more
      microbleeds (r = -0.78, p < 0.001). VEP P100 amplitudes, however, did not differ
      between CAA and controls (p = 0.45). There were trends toward reduced CO2
      reactivity in the middle cerebral artery (p = 0.10) and posterior cerebral artery
      (p = 0.08). CONCLUSIONS: Impaired blood flow responses in CAA are more evident
      using a task to activate the occipital lobe than the frontal lobe, consistent
      with the gradient of increasing vascular amyloid severity from frontal to
      occipital lobe seen in pathologic studies. Reduced fMRI responses in CAA are
      caused, at least partly, by impaired vascular reactivity, and are strongly
      correlated with other neuroimaging markers of CAA severity.

PMID- 24097811
TI  - A physiologic biomarker for cerebral amyloid angiopathy.
AB  - Cerebral amyloid angiopathy (CAA), a common small-vessel disease of older adults
      characterized by accumulation of amyloid-beta in leptomeningeal and cortical
      blood vessels, is a well-established cause of intracerebral hemorrhage.(1) Recent
      years have seen the emergence of clinical research reports establishing
      associations between CAA, ischemic brain injury, and vascular cognitive
      impairment (VCI). CAA patients had a higher load of chronic microvascular white
      matter hyperintensities (WMH), small infarcts, as well as a high degree of WMH
      progression.(2,3) A more recent report showed that vascular amyloid load strongly
      correlated with ischemic WMH in CAA.(4.) 

PMID- 24097812
TI  - Tumefactive multiple sclerosis and fingolimod: Immunotherapies and unintended
      consequences.
AB  - Our knowledge of the substantial complexities of the immune system and
      understanding of the immunopathogenesis of autoimmune diseases are increasing at
      such a rapid pace that it is impossible for the non-immunologist to stay abreast
      of the field. However, there are 2 general principles that are important for
      clinicians to keep in mind. One is that the immune system regulates itself. The
      effector arm of the adaptive immune system consists of subsets of lymphocytes
      that recognize and respond to non-self antigens expressed by infectious agents
      and malignant cells. Other subsets of lymphocytes regulate the effector arm of
      the immune system, thereby fine-tuning and limiting responses. A second principle
      is that autoimmune diseases, such as multiple sclerosis (MS), result from a
      failure of regulation of lymphocytes capable of reacting to self-antigens. Thus
      autoimmunity is conceived of as a loss of active tolerance to self-antigens
      related to activation of effector autoreactive lymphocytes and reduction in
      activity of regulatory lymphocytes. Much is known about the cellular subsets and
      molecules involved in autoimmune diseases, allowing rational development of
      immunotherapies. No better example of this exists than in the expanding
      armamentarium of immunotherapies for the treatment of MS. 

PMID- 24097813
TI  - Tumefactive MS lesions under fingolimod: a case report and literature review.
AB  - OBJECTIVE: To report about a possible association between fingolimod treatment
      and tumefactive demyelinating lesions (TDL) as seen in a patient developing
      repeated TDL on continued fingolimod therapy. METHODS: We performed serial
      clinical and radiologic assessments and immunophenotyping of blood and CSF immune
      cells. We also present a literature review about recent similar cases. RESULTS:
      Clinical course and radiologic findings were consistent with diagnosis of TDL.
      Immune cell phenotyping showed pronounced shifts in the immune cell composition
      related to fingolimod treatment. In addition, we observed a subset of highly
      differentiated effector cells (CD45R0negCCR7neg) within the CD8+ T-cell
      population, which was about 2-fold enriched in the CSF compared to the peripheral
      blood. CONCLUSION: Our observations add further evidence for the development of
      atypical demyelinating lesions in some patients receiving fingolimod. These might
      be related to a treatment-associated shift in the immunopathology of specifically
      susceptible individuals.

PMID- 24097814
TI  - Safety of IV thrombolysis in acute ischemic stroke related to Chagas disease.
AB  - OBJECTIVE: To determine the rate of symptomatic intracranial hemorrhage (SIH) and
      in-hospital mortality among patients with acute ischemic stroke related to Chagas
      disease (CD) treated with IV tissue plasminogen activator (TPA). METHODS: In this
      retrospective cohort study, consecutive stroke patients treated with IV TPA and
      routinely tested for CD were retrospectively selected from a single-center,
      hospital-based, prospective registry of acute stroke patients from 2001 to 2012.
      Demographic and clinical data were obtained from the registry as well as in
      hospital mortality. CT scans were blindly reviewed to assess the occurrence of
      hemorrhagic transformation. Among acute stroke patients who received IV TPA, we
      compared those with and without a positive serology for CD. RESULTS: Among 240
      patients treated with IV TPA, 174 had serologic testing for CD available. Of
      those, 24 patients (13.8%) had positive serology for CD. Patients with CD more
      frequently had heart failure (45.8% vs 14.7%; p < 0.01) and higher admission NIH
      Stroke Scale scores (19 [15-21] vs 13 [8-19]; p < 0.01) than patients with
      negative serology. The rates of SIH (4.2% vs 5.3%; odds ratio: 0.77; 95%
      confidence interval: 0.09-6.46; p = 0.99) and in-hospital death (16.7% vs 11.3%;
      odds ratio: 1.57; 95% confidence interval: 0.48-5.12; p = 0.50) were not higher
      among patients with CD. CONCLUSION: In the largest published series of patients
      with CD-related stroke treated with IV TPA, we have observed that IV thrombolysis
      was safely performed and showed no increase of SIH. The diagnosis of CD should
      not preclude IV thrombolysis in these patients.

PMID- 24097815
TI  - Negative-balance isolated pelvic perfusion in patients with incurable symptomatic
      rectal cancer: results and drug dose correlation to adverse events.
AB  - BACKGROUND: Drug leakage and lack of a drug-removal system have prevented
      clinical application of isolated pelvic perfusion (IPP). These barriers were
      overcome with negative-balance IPP (NIPP) in experimental pig models. Here, a
      phase 1 clinical study of NIPP was performed in patients with incurable
      symptomatic rectal cancer. PURPOSE: To establish a safe regimen of high-dose
      regional chemotherapy with NIPP using cisplatin in patients with incurable rectal
      cancer. MATERIAL AND METHODS: Between June 2004 and January 2007, NIPP therapy
      was performed for 23 patients (11 women, 12 men; mean age, 58 years). NIPP was
      routinely performed twice over a 4-week interval. Dose-limiting toxicities (DLTs)
      were defined using a 5 + 3 design, and cisplatin doses were escalated from 170
      mg/m(2), with a fixed 5-fluorouracil dose of 1000 mg/m(2). The grade of adverse
      events (AEs) at the first and second sessions of NIPP therapy, pharmacokinetics,
      and antitumor response were evaluated. RESULTS: No DLTs were observed during the
      first session of NIPP. However, at the second session, two patients experienced
      the DLT of neuropathy after administration of 200 mg/m(2) cisplatin. Therefore,
      190 mg/m(2) cisplatin was indicated as the maximum tolerated dose (MTD). The
      plasma pelvic-to-systemic exposure ratio was 18.4 based on the maximum
      concentration and 19.0 based on the concentration-time curve. Solid tumor
      responses included complete response in two patients, partial response in five
      patients, stable disease in 15 patients, and progressive disease in one patient.
      CONCLUSION: NIPP may offer the safe delivery of high-dose regional chemotherapy
      (MTD of 190 mg/m(2) cisplatin) with negligible AEs and effective control of tumor
      growth in patients with incurable rectal cancer.

PMID- 24097816
TI  - Factors predicting compliance to ecological momentary assessment among adolescent
      smokers.
AB  - INTRODUCTION: Ecological momentary assessments (EMAs) are increasingly used in
      smoking research to understand contextual and individual differences related to
      smoking and changes in smoking. To date, there has been little detailed research
      into the predictors of EMA compliance. However, patterns or predictors of
      compliance may affect key relationships under investigation and introduce sources
      of bias in results. The purpose of this study was to investigate predictors of
      compliance to random prompts among a sample of adolescents who had ever smoked.
      METHODS: Data for this study were drawn from a sample of 461 adolescents (9th and
      10th graders at baseline) participating in a longitudinal study of smoking
      escalation. We examined 2 outcomes: subject-level EMA compliance (overall rate of
      compliance over a week-long EMA wave), and in-the-moment prompt-level compliance
      to the most proximal random prompt. We investigated several covariates including
      gender, race, smoking rate, alcohol use, psychological symptomatology, home
      composition, mood, social context, time in study, inter-prompt interval, and
      location. RESULTS: At the overall subject level, higher mean negative affect,
      smoking rate, alcohol use, and male gender predicted lower compliance with random
      EMA prompts. At the prompt level, after controlling for significant subject-level
      predictors of compliance, increased positive affect, being outside of the home,
      and longer inter-prompt interval predicted lower momentary compliance.
      CONCLUSIONS: This study identifies several factors associated with overall and
      momentary EMA compliance among a sample of adolescents participating in a
      longitudinal study of smoking. We also propose a conceptual framework for
      investigating the contextual and momentary predictors of compliance within EMA
      studies.

PMID- 24097817
TI  - Staphylococcal dermatitis/pododermatitis and septicaemia in neonatal puppies.

PMID- 24097818
TI  - The association of middle ear effusion with trigeminal nerve mass lesions in
      dogs.
AB  - The trigeminal nerve is involved in the opening of the pharyngeal orifice of the
      Eustachian tube by operating the tensor veli palatini muscle. The hypothesis was
      investigated that middle ear effusion occurs in a more severe disease phenotype
      of canine trigeminal nerve mass lesions compared with dogs without middle ear
      effusion. Three observers reviewed canine MRIs with an MRI-diagnosis of
      trigeminal nerve mass lesion from three institutions. Various parameters
      describing the musculature innervated by the trigeminal nerve were scored and
      compared between dogs with and without middle ear effusion. Nineteen dogs met the
      inclusion criteria. Ipsilateral middle ear effusion was observed in 63 per cent
      (95% CI 48.4 per cent to 77.6 per cent) of the dogs. The size of the trigeminal
      nerve mass lesions was positively correlated with the severity of masticatory
      muscle mass loss (Spearman r=0.5, P=0.03). Dogs with middle ear effusion had a
      significantly increased generalised masticatory muscle mass loss (P=0.02) or
      tensor veli palatini muscle loss score (P=0.03) compared with those without.
      Larger trigeminal nerve mass lesions were associated with a greater degree of
      masticatory muscle mass loss. Masticatory muscle mass and, importantly, tensor
      veli palatini muscle mass was more severely affected in dogs with middle ear
      effusion suggesting an associated Eustachian tube dysfunction.

PMID- 24097819
TI  - Risk factors for antimicrobial resistance in Escherichia coli found in GB turkey
      flocks.
AB  - Four models are presented investigating risks present on Great Britain (GB)
      turkey farms in breeding and fattening flocks for ciprofloxacin and cephalosporin
      resistance. Risk factors for ciprofloxacin resistance in fattening flocks were
      sourcing of feed from national compounders, antimicrobial use in the flock and
      evidence of mice. Disinfection of floors and walls at depopulation, older flocks
      and division of the flock with partitions reduced the risk. In breeding farms
      holding over 10,000 birds, administration of fluoroquinolones within the last
      year and horses on the neighbouring farm all increased the risk, whereas
      replenishing foot dips more than once a week reduced the risk. For cephalosporin
      resistant Escherichia coli on fattening farms, being an independent farm, having
      a watercourse near the poultry houses, dividing the flock with partitions and
      providing staff with gloves reduced the risk. Factors that increased the risk
      included if staff worked with other livestock and if there were pigs on
      neighbouring farms. This work suggests that good hygiene and biosecurity, rodent
      control and responsible use of antimicrobials on turkey farms might help minimise
      the prevalence of fluoroquinolone and cephalosporin resistance in E coli, and
      restrict the spread of resistance genes to other organisms. 

PMID- 24097820
TI  - Interleukin-6 is required for pancreatic cancer progression by promoting MAPK
      signaling activation and oxidative stress resistance.
AB  - Pancreatic cancer, one of the deadliest human malignancies, is almost invariably
      associated with the presence of an oncogenic form of Kras. Mice expressing
      oncogenic Kras in the pancreas recapitulate the stepwise progression of the human
      disease. The inflammatory cytokine interleukin (IL)-6 is often expressed by
      multiple cell types within the tumor microenvironment. Here, we show that IL-6 is
      required for the maintenance and progression of pancreatic cancer precursor
      lesions. In fact, the lack of IL-6 completely ablates cancer progression even in
      presence of oncogenic Kras. Mechanistically, we show that IL-6 synergizes with
      oncogenic Kras to activate the reactive oxygen species detoxification program
      downstream of the mitogen-activated protein kinase/extracellular signal-regulated
      kinase (MAPK/ERK) signaling cascade. In addition, IL-6 regulates the inflammatory
      microenvironment of pancreatic cancer throughout its progression, providing
      several signals that are essential for carcinogenesis. Thus, IL-6 emerges as a
      key player at all stages of pancreatic carcinogenesis and a potential therapeutic
      target.

PMID- 24097822
TI  - The evolution of melanoma resistance reveals therapeutic opportunities.
AB  - The RAS-RAF-MEK-ERK pathway is a key driver of proliferation and survival signals
      in tumor cells and has been the focus of intense drug development efforts over
      the past 20 years. The recent regulatory approval of RAF inhibitors and a MAP-ERK
      kinase (MEK) inhibitor for metastatic melanoma provides clinical validation of
      tumor dependency on this pathway. Unfortunately, the therapeutic benefit of these
      agents is often short lived and resistance develops within a matter of months.
      Preclinical models of resistance to vemurafenib have provided critical insights
      into predicting, validating, and characterizing potential mechanisms. A key
      observation has been that vemurafenib-resistant tumor cells suffer a fitness
      deficit in the absence of drug treatment and this led to the predication that
      modulating the selective pressure of drug treatment through intermittent dosing
      could delay or prevent the emergence of resistant tumors. Most importantly, the
      preclinical data are supported by observations in vemurafenib-treated patients
      with melanoma providing a strong rationale for clinical testing of alternative
      dosing regimens.

PMID- 24097824
TI  - Twenty-fifth annual Pezcoller Symposium: Metabolism and tumorigenesis.
AB  - Choking cancer via inhibition of metabolic enzymes essential for tumor but
      dispensable in normal tissues was discussed as was the altered metabolism in
      cancer cells related to: tumor suppressor protein (pVHL) function, the histone
      acetylation dependence upon glucose, the epigenomic reprogramming of acetyl CoA
      synthesis, the plasticity of aging mechanisms, and the metabolism orchestration
      in macrophage polarization. The p53 and p73 pathways role in metabolic
      adaptation, the effects on growth of AMP-dependent kinase, the growth regulation
      by the mTOR pathways, and the bioenergetics requirements of cancer cells were
      also discussed. A novel computational model of personalized metabolic changes in
      cancer was outlined with applications in patients with breast cancer. Imaging
      metabolic characteristics of tumors by MRI and (13)C-nuclear magnetic resonance
      was described. The cancer metabolism regulation related to O-linked beta-N
      acetylglucosame was described. DNA hypermethylation and impaired hematopoietic
      differentiation in AML after isocitrate dehydrogenase 1/2 mutation and 2
      hydroxyglutarate increases were outlined.

PMID- 24097821
TI  - Novel modeling of cancer cell signaling pathways enables systematic drug
      repositioning for distinct breast cancer metastases.
AB  - A new type of signaling network element, called cancer signaling bridges (CSB),
      has been shown to have the potential for systematic and fast-tracked drug
      repositioning. On the basis of CSBs, we developed a computational model to derive
      specific downstream signaling pathways that reveal previously unknown target
      disease connections and new mechanisms for specific cancer subtypes. The model
      enables us to reposition drugs based on available patient gene expression data.
      We applied this model to repurpose known or shelved drugs for brain, lung, and
      bone metastases of breast cancer with the hypothesis that cancer subtypes have
      their own specific signaling mechanisms. To test the hypothesis, we addressed
      specific CSBs for each metastasis that satisfy (i) CSB proteins are activated by
      the maximal number of enriched signaling pathways specific to a given metastasis,
      and (ii) CSB proteins are involved in the most differential expressed coding
      genes specific to each breast cancer metastasis. The identified signaling
      networks for the three types of breast cancer metastases contain 31, 15, and 18
      proteins and are used to reposition 15, 9, and 2 drug candidates for the brain,
      lung, and bone metastases. We conducted both in vitro and in vivo preclinical
      experiments as well as analysis on patient tumor specimens to evaluate the
      targets and repositioned drugs. Of special note, we found that the Food and Drug
      Administration-approved drugs, sunitinib and dasatinib, prohibit brain metastases
      derived from breast cancer, addressing one particularly challenging aspect of
      this disease.

PMID- 24097825
TI  - Contribution of Bcl-2 phosphorylation to Bak binding and drug resistance.
AB  - Bcl-2 is phosphorylated on Ser(70) after treatment of cells with spindle poisons.
      On the basis of effects observed in cells overexpressing Bcl-2 S70E or S70A
      mutants, various studies have concluded that Ser(70) phosphorylation either
      enhances or diminishes Bcl-2 function. In the present study, the ability of
      phosphorylated Bcl-2, as well as the S70E and S70A mutants, to bind and
      neutralize proapoptotic Bcl-2 family members under cell-free conditions and in
      intact cells was examined in an attempt to resolve this controversy. Surface
      plasmon resonance indicated that phosphorylated Bcl-2, Bcl-2 S70E, and Bcl-2 S70A
      exhibit enhanced binding to Bim and Bak compared with unmodified Bcl-2. This
      enhanced binding reflected a readily detectable conformation change in the loop
      domain of Bcl-2. Furthermore, Bcl-2 S70E and S70A bound more Bak and Bim than
      wild-type Bcl-2 in pull-downs and afforded greater protection against several
      chemotherapeutic agents. Importantly, binding of endogenous Bcl-2 to Bim also
      increased during mitosis, when Bcl-2 is endogenously phosphorylated, and
      disruption of this mitotic Bcl-2/Bim binding with navitoclax or ABT-199, like Bcl
      2 downregulation, enhanced the cytotoxicity of paclitaxel. Collectively, these
      results provide not only a mechanistic basis for the enhanced antiapoptotic
      activity of phosphorylated Bcl-2, but also an explanation for the ability of BH3
      mimetics to enhance taxane sensitivity.

PMID- 24097826
TI  - RSK isoforms in cancer cell invasion and metastasis.
AB  - Metastasis, the spreading of cancer cells from a primary tumor to secondary sites
      throughout the body, is the primary cause of death for patients with cancer. New
      therapies that prevent invasion and metastasis in combination with current
      treatments could therefore significantly reduce cancer recurrence and morbidity.
      Metastasis is driven by altered signaling pathways that induce changes in cell
      cell adhesion, the cytoskeleton, integrin function, protease expression,
      epithelial-to-mesenchymal transition and cell survival. The ribosomal S6 kinase
      (RSK) family of kinases is a group of extracellular signal-regulated
      kinase/mitogen-activated protein kinase (ERK/MAPK) effectors that can regulate
      these steps of metastasis by phosphorylating both nuclear and cytoplasmic
      targets. However, our understanding of RSK function in metastasis remains
      incomplete and is complicated by the fact that the four RSK isoforms perform
      nonredundant, sometimes opposing functions. Although some isoforms promote cell
      motility and invasion by altering transcription and integrin activity, others
      impair cell motility and invasion through effects on the actin cytoskeleton. The
      mechanism of RSK action depends both on the isoform and the cancer type. However,
      despite the variance in RSK-mediated outcomes, chemical inhibition of this group
      of kinases has proven effective in blocking invasion and metastasis of several
      solid tumors in preclinical models. RSKs are therefore a promising drug target
      for antimetastatic cancer treatments that could supplement and improve current
      therapeutic approaches. This review highlights contradiction and agreement in the
      current data on the function of RSK isoforms in metastasis and suggests ways
      forward in developing RSK inhibitors as new antimetastasis drugs.

PMID- 24097827
TI  - Time-dependent diffusion tensor changes of optic nerve in patients with indirect
      traumatic optic neuropathy.
AB  - BACKGROUND: Indirect traumatic optic neuropathy (ITON) is a devastating cause of
      permanent visual loss. Axonal degeneration, the characteristic pathological
      change of ITON, cannot be assessed by conventional imaging. Diffusion tensor
      imaging (DTI) has been widely used as a sensitive non-invasive imaging technique
      to obtain information on axonal integrity. PURPOSE: To study time-dependent
      changes in ITON patients with DTI and to provide imaging evidence for clinical
      diagnosis and therapy. MATERIAL AND METHODS: We enrolled 28 subjects with
      unilateral ITON who underwent detailed ocular examinations and magnetic resonance
      imaging (MRI) examinations. The differences between injured optic nerve (ON) and
      contralateral ON were tested. The patients were divided into three groups based
      on time (from injury to examination). Groups 1, 2, and 3 corresponded to the time
      taken from injury to examination: <7 days, 7-30 days, and >30 days, respectively.
      DT magnetic resonance imaging (MRI) differences among the groups were compared,
      including the relationship between diffusion parameters and mean thicknesses of
      the peripapillary retinal nerve fiber layer (RNFL) and ganglion cell complex
      (GCC) in the macular area. RESULTS: Compared with contralateral ON, we observed
      reduced fractional anisotropy (FA) of injured nerves in group 2. Reduced FA and
      decreased axial diffusivity (lambda//) and increased radial diffusivity (lambda?)
      and mean diffusivity (MD) of injured nerves were observed in group 3. The mean FA
      value of injured nerves showed a progressive decreasing trend, and mean lambda?
      value exhibited a progressive increasing trend. For injured eyes, the MD and
      lambda? increases strongly correlated with the decreased mean thicknesses of RNFL
      and GCC. Conversely, FA was significantly associated with mean RNFL thickness.
      CONCLUSION: DT-MRI parameters could be useful biomarkers in detecting ON changes
      in ITON patients.

PMID- 24097828
TI  - Genetically-engineered mesenchymal stem cells transfected with human HCN1 gene to
      create cardiac pacemaker cells.
AB  - OBJECTIVE: To test the proof-of-principle that genetically-engineered mesenchymal
      stem cells (MSCs) transfected with the human hyperpolarization-activated cyclic
      nucleotide-gated channel 1 (hHCN1) gene can be modified to become cardiac
      pacemaker cells. METHODS: MSCs were transfected with the hHCN1 gene using
      lentiviral-based transfection. The expressed pacemaker current (I(f)) in hHCN1
      transfected MSCs was recorded using whole-cell patch-clamp analysis. The effect
      of the hHCN1-transfected MSCs on cardiomyocyte excitability was determined by
      coculturing the MSCs with neonatal rabbit ventricular myocytes (NRVM). The
      spontaneous action potentials of the NRVM were recorded by whole-cell current
      clamp analysis. RESULTS: A high level time- and voltage-dependent inward
      hyperpolarization current that was inhibited by 4 mM caesium chloride was
      detected in hHCN1-transfected MSCs, suggesting that the HCN1 proteins acted as
      I(f) channels in MSCs. The mean +/- SE beating frequency in NRVMs cocultured with
      control MSCs transfected with the pcDNA3 plasmid control was 82 +/- 8 beats/min
      (n = 5) compared with 129 +/- 11 beats/min (n = 5) in NRVMs cocultured with hHCN1
      transfected MSCs. CONCLUSIONS: Genetically-engineered MSCs transfected with the
      hHCN1 gene can be modified to become cardiac pacemaker cells.

PMID- 24097829
TI  - Inhibition of proliferation and invasiveness of ovarian cancer C13* cells by a
      poly(ADP-ribose) polymerase inhibitor and the role of nuclear factor-kappaB.
AB  - OBJECTIVE: To investigate the effect of the poly(ADP-ribose) polymerase-1 (PARP
      1) inhibitor PJ34 on the proliferation and invasiveness of ovarian cancer C13*
      cells and the role of nuclear factor-kappaB (NF-kappaB). METHODS: Proliferation
      of C13* cells was measured using a 3 -(4,5-dimethylthazol-2-yl)-2,5-diphenyl
      tetrazolium bromide assay after incubation with PJ34 at different concentrations
      and for different treatment durations. In addition, expression of PARP-1 and the
      NF-kappaB p65 subunit after treatment with PJ34 was measured using Western blot
      and immunocytochemistry. The effect of PJ34 on cell invasiveness was examined
      using a transwell invasion assay. RESULTS: PJ34 inhibited proliferation of C13*
      cells in a time- and dose-dependent manner. PJ34 treatment was also associated
      with a dose-dependent decrease in PARP-1 and NF-kappaB p65 expression and
      attenuated invasiveness of C13* cells. PARP-1 expression was positively
      correlated with NF-kappaB p65 expression. CONCLUSION: The PARP-1 inhibitor PJ34
      can markedly inhibit the proliferation and invasiveness of C13* cells, possibly
      due to PARP-1-mediated attenuation of NF-kappaB activity.

PMID- 24097830
TI  - Effects of Ureaplasma urealyticum lipid-associated membrane proteins on
      rheumatoid arthritis synovial fibroblasts.
AB  - OBJECTIVES: As an infectious agent might play a role in rheumatoid arthritis (RA)
      development, this study investigated effects of Ureaplasma urealyticum lipid
      associated membrane proteins (UuLAMPs) on RA synovial fibroblast (RASF)
      proliferation, and tumour necrosis factor (TNF)-alpha and interleukin (IL)-1beta
      production by THP-1 macrophages. Possible immunogenic proteins in UuLAMPs were
      identified. METHODS: RASFs were cultured from synovial tissue from donors with
      RA. Serum samples from donors with/without RA and with/without U. urealyticum
      infection were used for immunogenicity analyses. THP-1 macrophages served as a
      model for synovial macrophages. TNF-alpha and IL-1beta mRNA levels were assessed
      using reverse transcription-polymerase chain reaction; protein levels were
      estimated using enzyme-linked immunosorbent assay. UuLAMPs underwent separation
      and Western blot analyses. RESULTS: UuLAMPs (0.025-0.4 ug/ml) stimulated RASF
      proliferation in a dose- and time-dependent manner, and increased TNF-alpha and
      IL-1beta levels in THP-1 macrophages. Several immunogenic UuLAMPs were
      identified, but antibodies to a 25 kDa protein were only found in RA patients
      with U. urealyticum infection. CONCLUSIONS: UuLAMPs might induce RASF
      proliferation and proinflammatory cytokine secretion in synovium from RA
      patients. A 25 kDa U. urealyticum protein might act as a cross-reactive antigen.

PMID- 24097832
TI  - Evaluation of the DNA-dependent RNA polymerase beta-subunit gene (rpoB) for
      phytoplasma classification and phylogeny.
AB  - Phytoplasmas are classified into 16Sr groups and subgroups and 'Candidatus
      Phytoplasma' species, largely or entirely based on analysis of 16S rRNA gene
      sequences. Yet, distinctions among closely related 'Ca. Phytoplasma' species and
      strains based on 16S rRNA genes alone have limitations imposed by the high degree
      of rRNA nucleotide sequence conservation across diverse phytoplasma lineages and
      by the presence in a phytoplasma genome of two, sometimes sequence-heterogeneous,
      copies of the 16S rRNA gene. Since the DNA-dependent RNA polymerase (DpRp) beta
      subunit gene (rpoB) exists as a single copy in the phytoplasma genome, we
      explored the use of rpoB for phytoplasma classification and phylogenetic
      analysis. We sequenced a clover phyllody (CPh) phytoplasma genetic locus
      containing ribosomal protein genes, a complete rpoB gene and a partial rpoC gene
      encoding the beta'-subunit of DpRp. Primers and reaction conditions were designed
      for PCR-mediated amplification of rpoB gene fragments from diverse phytoplasmas.
      The rpoB gene sequences from phytoplasmas classified in groups 16SrI, 16SrII,
      16SrIII, 16SrX and 16SrXII were subjected to sequence similarity and phylogenetic
      analyses. The rpoB gene sequences were more variable than 16S rRNA gene
      sequences, more clearly distinguishing among phytoplasma lineages. Phylogenetic
      trees based on 16S rRNA and rpoB gene sequences had similar topologies, and
      branch lengths in the rpoB tree facilitated distinctions among closely related
      phytoplasmas. Virtual RFLP analysis of rpoB gene sequences also improved
      distinctions among closely related lineages. The results indicate that the rpoB
      gene provides a useful additional marker for phytoplasma classification that
      should facilitate studies of disease aetiology and epidemiology. 

PMID- 24097833
TI  - Taxonomic study of the genera Halogeometricum and Halosarcina: transfer of
      Halosarcina limi and Halosarcina pallida to the genus Halogeometricum as
      Halogeometricum limi comb. nov. and Halogeometricum pallidum comb. nov.,
      respectively.
AB  - Members of the haloarchaeal genera Halosarcina and Halogeometricum (family
      Halobacteriaceae) are closely related to each other and show 96.6-98 % 16S rRNA
      gene sequence similarity. This is higher than the accepted threshold value (95 %)
      to separate two genera, and a taxonomic study using a polyphasic approach of all
      four members of the two genera was conducted to clarify their relationships.
      Polar lipid profiles indicated that Halogeometricum rufum RO1-4(T), Halosarcina
      pallida BZ256(T) and Halosarcina limi RO1-6(T) are related more to each other
      than to Halogeometricum borinquense CGMCC 1.6168(T). Phylogenetic analyses using
      the sequences of three different genes (16S rRNA gene, rpoB' and EF-2) strongly
      supported the monophyly of these four species, showing that they formed a
      distinct clade, separate from the related genera Halopelagius, Halobellus,
      Haloquadratum, Haloferax and Halogranum. The results indicate that the four
      species should be assigned to the same genus, and it is proposed that Halosarcina
      pallida and Halosarcina limi be transferred to the genus Halogeometricum as
      Halogeometricum pallidum comb. nov. (type strain, BZ256(T) = KCTC 4017(T) = JCM
      14848(T)) and Halogeometricum limi comb. nov. (type strain, RO1-6(T) = CGMCC
      1.8711(T) = JCM 16054(T)). 

PMID- 24097834
TI  - Genome sequence analyses show that Neisseria oralis is the same species as
      'Neisseria mucosa var. heidelbergensis'.
AB  - Phylogenies generated from whole genome sequence (WGS) data provide definitive
      means of bacterial isolate characterization for typing and taxonomy. The species
      status of strains recently defined with conventional taxonomic approaches as
      representing Neisseria oralis was examined by the analysis of sequences derived
      from WGS data, specifically: (i) 53 Neisseria ribosomal protein subunit (rps)
      genes (ribosomal multi-locus sequence typing, rMLST); and (ii) 246 Neisseria core
      genes (core genome MLST, cgMLST). These data were compared with phylogenies
      derived from 16S and 23S rRNA gene sequences, demonstrating that the N. oralis
      strains were monophyletic with strains described previously as representing
      'Neisseria mucosa var. heidelbergensis' and that this group was of equivalent
      taxonomic status to other well-described species of the genus Neisseria.
      Phylogenetic analyses also indicated that Neisseria sicca and Neisseria macacae
      should be considered the same species as Neisseria mucosa and that Neisseria
      flavescens should be considered the same species as Neisseria subflava. Analyses
      using rMLST showed that some strains currently defined as belonging to the genus
      Neisseria were more closely related to species belonging to other genera within
      the family; however, whole genome analysis of a more comprehensive selection of
      strains from within the family Neisseriaceae would be necessary to confirm this.
      We suggest that strains previously identified as representing 'N. mucosa var.
      heidelbergensis' and deposited in culture collections should be renamed N.
      oralis. Finally, one of the strains of N. oralis was able to ferment lactose, due
      to the presence of beta-galactosidase and lactose permease genes, a
      characteristic previously thought to be unique to Neisseria lactamica, which
      therefore cannot be thought of as diagnostic for this species; however, the rMLST
      and cgMLST analyses confirm that N. oralis is most closely related to N. mucosa. 

PMID- 24097837
TI  - The allegedly abusive surrogate.

PMID- 24097838
TI  - Barriers to end-of-life care for African Americans from the providers'
      perspective: opportunity for intervention development.
AB  - Research has shown that African Americans (AAs) are less likely to complete
      advance directives and enroll in hospice. We examined barriers to use of these
      end-of-life (EOL) care options by conducting semi-structured interviews with
      hospice and palliative medicine providers and leaders of a national health care
      organization. Barriers identified included: lack of knowledge about prognosis,
      desires for aggressive treatment, family members resistance to accepting hospice,
      and lack of insurance. Providers believed that acceptance of EOL care options
      among AAs could be improved by increasing cultural sensitivity though education
      and training initiatives, and increasing staff diversity. Respondents did not
      have programs currently in place to increase awareness of EOL care options for
      underrepresented minorities, but felt that there was a need to develop these
      types of programs. These data can be used in future research endeavors to create
      interventions designed to increase awareness of EOL care options for AAs and
      other underrepresented minorities. 

PMID- 24097839
TI  - End-of-life care policies and practices in pediatric skilled nursing facilities.
AB  - Although most children with intellectual and developmental disabilities reside in
      the community, a subset of children with severe intellectual disability and
      complex medical needs reside in pediatric skilled nursing facilities. These
      children have elevated mortality with end-of-life care (EOLC) routinely provided.
      The present study explored policies and practice in such settings by surveying
      administrators, nursing directors, and medical directors in facilities across the
      United States. In addition to EOLC policies and practices, staff reported on
      their understanding of definitions of do-not-resuscitate orders, family
      involvement in EOLC planning, and the availability of in-service training. The
      presence of an official EOLC policy was associated with higher ratings of
      perception of effectiveness among staff. Staff felt more prepared and comfortable
      providing EOLC when in-service training was provided. 

PMID- 24097840
TI  - Examining the effect of the case management model on patient results in the
      palliative care of patients with cancer.
AB  - PURPOSE: We aimed to investigate the improvement in symptoms, quality of life,
      patient and family satisfaction with care, and direct costs resulting from a
      palliative care program based case management model. METHODS: The research was
      implemented at the Medical Oncology Clinic hospital of a University between
      September 2009 and September 2011. The research sample consisted of a total of 44
      patients (22 control and 22 intervention group). The research tools were the
      Edmonton Symptom Diagnosis System, the Karnofsky Performance Scale, the EORTCQLQ
      C30 Quality of Life Scale, a patient and family satisfaction form, and a patient
      cost record form. RESULTS: The difference between total symptom mean scores and
      the sub-dimension symptoms of pain, fatigue, nausea, depression, anxiety, lack of
      appetite, lethargy, well-being, dyspnea, and constipation post-hospitalization
      and post-discharge of patients in the control and experimental groups were found
      to be statistically significant (p < 0.05). The level of decrease in symptom
      severity in the experimental group patients was more than in the control group (p
      < 0.000). The satisfaction level of patients and family in the palliative care
      based case management service was higher than that for conventional service in
      the control group (p < 0.05). No statistical difference was detected between the
      experimental and control groups regarding health costs and duration of
      hospitalization (p > 0.05). CONCLUSION: We provided a better symptom control,
      improved the patient s quality of life (excluding physical and congnitive
      functions), and patient and family satisfaction levels were higher in the
      palliative care based case management intervention group, but direct health costs
      were not affected.

PMID- 24097841
TI  - Beliefs, stigma and discrimination associated with mental health problems in
      Uganda: implications for theory and practice.
AB  - BACKGROUND: There are major gaps in knowledge about beliefs, stigma and
      discrimination in Uganda, including the relationship between different cultural
      beliefs and stigmatising responses, how stigma and beliefs result in
      discrimination and the impact of social factors such as gender, poverty and
      ethnic conflict. AIM: This exploratory study aims to understand beliefs, stigma
      and discrimination associated with mental health in Uganda in more depth from the
      perspectives of different stakeholders. METHODS: Focus groups and interviews were
      undertaken with mental health activists, policymakers, practitioners, non
      governmental and human rights organisations, journalists and academics. RESULTS:
      Stigma was reported by individuals, families, communities and institutions,
      including health services. The study also found stigmatising beliefs linked to
      traditional, religious and medical explanatory frameworks, high levels of
      'associated stigma', common mental health problems rarely medicalised and
      discrimination linked to poverty, gender and conflict. CONCLUSIONS: The findings
      suggest the need to address stigma in their cultural and social context,
      alongside other human rights initiatives.

PMID- 24097842
TI  - Predictors of insight in first-episode schizophrenia: a 5-year cohort study from
      India.
AB  - BACKGROUND AND AIMS: There is a dearth of data on the predictors of insight in
      schizophrenia. This study attempted to assess the predictors of insight in a
      cohort of first-episode schizophrenia followed up over 5 years. METHODS: Patients
      diagnosed to have Diagnostic and statistical manual of mental disorders (4th ed.;
      DSM-IV) schizophrenia (n = 131) were assessed prospectively for insight,
      psychopathology and explanatory models of illness over a 5-year period using
      standard instruments. Multiple linear regression and generalized estimating
      equations (GEE) were employed to assess predictors of insight. RESULTS: We could
      follow up 95 (72.5%) patients, 5 years after recruitment. A total of 65 of these
      patients interviewed at 60 months (68.4%) achieved remission. Cross-sectional
      evaluations suggest a relationship between insight, psychosis rating and
      explanatory models of illness with good insight and medical models associated
      with good outcome. However, baseline and early illness data do not predict
      insight scores at 5 years. Serial longitudinal assessment of insight is
      negatively associated with Brief Psychiatric Rating Scale (BPRS) scores and
      positively associated with the number of nonmedical explanatory models of illness
      held by patients. CONCLUSION: These findings argue that insight and explanatory
      models of illness are secondary to psychopathology, course and outcome. They are
      dependent on the trajectory of the person's illness, are not independent of the
      condition and call for multifaceted understanding of the issues.

PMID- 24097843
TI  - Raltegravir pharmacokinetics in HIV/HCV-coinfected patients with advanced liver
      cirrhosis (Child-Pugh C).
AB  - OBJECTIVES: To describe raltegravir pharmacokinetics at steady-state in
      HIV/hepatitis C virus (HCV)-coinfected patients under antiretroviral (ARV)
      treatment with (n = 5) and without (n = 5) advanced liver cirrhosis (Child-Pugh
      C). METHODS: This was a non-randomized, Phase I, parallel-assignment, open-label
      pharmacokinetic study in HIV/HCV-coinfected patients with Child-Pugh grade C
      hepatic cirrhosis. We recruited clinically stable HIV/HCV-coinfected adult
      patients with controlled HIV viraemia (<50 copies/mL) for at least 6 months.
      Raltegravir (400 mg twice daily) was added under fasting conditions for 5 days to
      the successful ritonavir-boosted protease inhibitor-based ARV regimen. The trial
      was registered in the ClinicalTrials.gov database (NCT01289951) (LIVERAL).
      RESULTS: Raltegravir AUC0-12 and C12 were increased 1.72-fold (90% CI, 1.02 to
      2.92) and 6.58-fold (90% CI, 2.92 to14.85), respectively, in patients with
      advanced liver cirrhosis. No safety issues were identified and raltegravir was
      well tolerated by all patients. CONCLUSIONS: Raltegravir plasma levels are
      increased in HIV/HCV-coinfected patients with advanced liver cirrhosis (Child
      Pugh C). Despite the higher exposure, raltegravir was safe and well tolerated.

PMID- 24097844
TI  - Costs of psychosis in 2010: findings from the second Australian National Survey
      of Psychosis.
AB  - OBJECTIVES: To estimate the annual costs of psychosis in Australia from societal
      and government perspectives and assess whether average costs per person differ by
      principal service provider at time of census. METHODS: Costs of psychosis
      encompassing health sector costs, other sector costs, and productivity losses
      were assessed for 2010 using a prevalence-based, bottom-up approach. Resource use
      data were obtained from the second Australian National Survey of Psychosis and
      unit costs were from government and non-government organization (NGO) sources.
      Costs to society were assessed by principal service provider at census: public
      specialized mental health services (PSMHS) and NGOs during the census month
      (current clients), and PSMHS in the 11 months preceding census (recent clients),
      and any differences were ascertained. RESULTS: The average annual costs of
      psychosis to society are estimated at $77,297 per affected individual, comprising
      $40,941 in lost productivity, $21,714 in health sector costs, and $14,642 in
      other sector costs. Health sector costs are 3.9-times higher than those for the
      average Australian. Psychosis costs Australian society $4.91 billion per annum,
      and the Australian government almost $3.52 billion per annum. There are
      significant differences between principal service providers for each cost
      category. Current PSMHS clients had the highest health sector costs overall, and
      the highest mental health ambulatory, inpatient, and antipsychotic medication
      costs specifically. NGO clients had the highest other sector costs overall and
      the highest NGO assistance, supported employment, and supported accommodation
      costs. Recent PSMHS clients had the lowest productivity losses for reduced
      participation and the highest costs for absenteeism and presenteeism.
      CONCLUSIONS: The costs of psychosis are broad ranging and very high. Development
      and implementation of cost-effective prevention, treatment, and support
      strategies is critical to maximizing the efficiency of service delivery. A needs
      based framework based on principal service provider and recency of contact may
      facilitate this process.

PMID- 24097845
TI  - The subcortical connectome: hubs, spokes and the space between - a vision for
      further research in neurodegenerative disease.

PMID- 24097846
TI  - Evaluating Parental Disagreement in ADHD Diagnosis: Can We Rely on a Single
      Report From Home?
AB  - OBJECTIVE: Few studies assessed factors associated with the
      agreement/disagreement between fathers and mothers when rating ADHD symptoms of
      their offspring. METHOD: Teachers and both parents assessed a referred sample of
      98 children and adolescents aged 6 to 16 years ( M age = 9.79, SD = 2.59) using
      the Swanson, Nolan, and Pelham (SNAP-IV) rating scale. The agreement was assessed
      for each of the items of the scale and correlated with variables measuring
      children's features, socioeconomic adversity, family functioning, and parental
      psychopathology. RESULTS: Mean agreement between parents was moderate for the
      inattentive and good for the hyperactive-impulsive construct. Mothers tended to
      report more symptoms than fathers. The agreement was lower in those families
      where parents had discrepant educational levels. CONCLUSION: Our findings suggest
      a significant cross-informant disagreement between parents on symptoms of ADHD.
      Discrepant parental education has a relevant role in explaining parental
      disagreement in reporting ADHD symptoms.

PMID- 24097847
TI  - Neurobiology of ADHD From Childhood to Adulthood: Findings of Imaging Methods.
AB  - OBJECTIVE: To review the pattern of morphological and functional brain changes in
      both children and adults with ADHD that emerges from the recent literature. In
      addition, the task of the present review is to explore how to understand the
      nature of the brain changes. METHODS: Literature review. RESULTS: Neuroimaging
      studies provide a multitude of information that currently allows us to expand the
      notions of ADHD neurobiology beyond its traditional understanding as a
      manifestation of frontostriatal dysfunction. They point to disorders of several
      other areas of the brain, particularly the anterior cingulum, the dorsolateral as
      well as ventrolateral prefrontal cortex, the orbitofrontal cortex, the superior
      parietal regions, the caudate nucleus, the thalamus, the amygdala and the
      cerebellum. Imaging studies point to the persistence of changes in both brain
      structure and function into adulthood, although there might be a tendency for
      improvement of caudate nucleus pathology. Changes in neuronal (dendritic)
      plasticity, which are under the modulatory influence of the dopaminergic system,
      may be in the background of disorders of brain morphology and anatomical
      connectivity with subsequent brain dysfunction. Growing evidence suggest that
      methylphenidate treatment can lead to improvement of brain changes seen in
      neuroimaging by its positive effect on neuroplasticity. CONCLUSION: Changes in
      neuronal plasticity may be behind persisting brain changes in ADHD. Current
      treatment approaches seem to improve these neuroplastic processes, and,
      therefore, may have a positive effect on the neuropathology of ADHD.

PMID- 24097848
TI  - A wide clinical phenotype spectrum in patients with ATP1A2 mutations.
AB  - The clinical spectrum associated with ATP1A2 mutations is expanding and includes
      familial hemiplegic migraine, alternating hemiplegia of childhood, and epilepsy.
      We have identified a novel c.1766T>C. (Ile589Thr) heterozygous mutation in the
      ATP1A2 gene in a Saudi kindred with hemiplegic attacks and seizures. Our findings
      broaden the phenotypic spectrum of patients with ATP1A2 mutations. 

PMID- 24097850
TI  - Pediatric anti-N-methyl-D-aspartate (NMDA) receptor encephalitis: experience of a
      tertiary care teaching center from north India.
AB  - Anti-N-methyl-D-aspartate (NMDA) receptor encephalitis is characterized by acute-
      or subacute-onset encephalopathy with extrapyramidal, psychiatric, and epileptic
      manifestations. Diagnosis is confirmed by positive antibodies to NMDA receptor in
      cerebrospinal fluid and serum. Eleven pediatric cases presented over a 2-year
      period at a tertiary care teaching hospital in North India. The average age at
      presentation was 9 years (range: 2.5 to 18 years, median: 10 years) with a slight
      female predominance (1.2:1). The common modes of presentation were progressive
      extrapyramidal syndrome with global neuroregression in 45% (5 of 11),
      epileptiform encephalopathy in 27% (3 of 11), and an overlap between the 2 in 27%
      (3 of 11). Fifty-eight percent showed significant response to steroids and
      intravenous immunoglobulin. This entity should be considered in an acute- or
      subacute-onset encephalopathy if common infectious etiologies are ruled out and
      there are specific clinical pointers. Early diagnosis and treatment significantly
      improves the outcome.

PMID- 24097849
TI  - Nutritional practices at a glance: spinal muscular atrophy type I nutrition
      survey findings.
AB  - Proactive nutritional management for children with spinal muscular atrophy type I
      can provide insight into improved spinal muscular atrophy care. This
      observational study consisted of a nutritional and medical history survey of
      children with spinal muscular atrophy type I collected in 2009-2011. Forty-four
      caregiver survey responses were evaluated using descriptive statistics. Average
      age of spinal muscular atrophy type I subjects was 5 years (5 mo-16 y). The
      subject cohort was composed of 22 males, 21 females, and 1 unreported. Nutrition
      support via feeding tube was utilized by 43 of 44 subjects. A majority of
      respondents reported using elemental or semi-elemental formula for subjects'
      essential caloric intake (34 of 44). Formula intolerance issues were reported by
      many caregivers (27 of 44). Half of caregivers implemented dietary changes on
      their own or with guidance from other families; 15 caregivers consulted a
      registered dietitian. Survey responses and comments indicate need for evidence
      based nutritional guidelines for spinal muscular atrophy. 

PMID- 24097851
TI  - Peripheral facial palsy in children.
AB  - The aim of this study is to evaluate the types and clinical characteristics of
      peripheral facial palsy in children. The hospital charts of children diagnosed
      with peripheral facial palsy were reviewed retrospectively. A total of 81
      children (42 female and 39 male) with a mean age of 9.2 +/- 4.3 years were
      included in the study. Causes of facial palsy were 65 (80.2%) idiopathic (Bell
      palsy) facial palsy, 9 (11.1%) otitis media/mastoiditis, and tumor, trauma,
      congenital facial palsy, chickenpox, Melkersson-Rosenthal syndrome, enlarged
      lymph nodes, and familial Mediterranean fever (each 1; 1.2%). Five (6.1%)
      patients had recurrent attacks. In patients with Bell palsy, female/male and
      right/left ratios were 36/29 and 35/30, respectively. Of them, 31 (47.7%) had a
      history of preceding infection. The overall rate of complete recovery was 98.4%.
      A wide variety of disorders can present with peripheral facial palsy in children.
      Therefore, careful investigation and differential diagnosis is essential. 

PMID- 24097852
TI  - Food selectivity in autism spectrum disorders: a systematic review.
AB  - Autism spectrum disorders are characterized by difficulties with reciprocal
      social interactions and restricted patterns of behavior and interest; one of
      these characteristic behaviors is food selectivity. The objective of this study
      was to perform a systematic review of the literature published between 1970 and
      2013 concerning this eating behavior. The articles identified were analyzed in
      terms of sample size, study design, and criteria for assessment and intervention,
      as well as the results, level of evidence and grade of recommendation. The main
      search was conducted in Medline, Cochrane Library, Scielo, ScienceDirect, and
      Embase). There is empirical evidence and an overall scientific consensus
      supporting an association between food selectivity and autism spectrum disorders.

PMID- 24097853
TI  - Comparison of the use of adipose tissue-derived and bone marrow-derived stem
      cells for rapid bone regeneration.
AB  - Stem cell-based bone tissue engineering has been recognized as a new strategy for
      maxillary sinus floor elevation. More rapid bone formation may enhance this
      technique when simultaneous dental implant placement is desired. Adipose tissue
      derived stem cells (ADSCs) and bone marrow stem cells (BMSCs) are the most well
      characterized cell sources for bone regeneration, but comparative studies on the
      osteogenic potential of these cells have yielded conflicting conclusions. This
      study aimed to compare the rapid bone formation capacity of ADSCs and BMSCs in a
      canine sinus floor augmentation model. In in vitro studies, BMSCs had a higher
      proliferative ability and greater osteogenic differentiation potential at both
      the mRNA and protein levels. When GFP-labeled cells on calcium phosphate cement
      (CPC) scaffolds were implanted subcutaneously into nude mice, both ADSCs and
      BMSCs survived for 4 wks, but only BMSCs formed new bone. Furthermore, according
      to sequential fluorescence labeling results for the canine sinus, BMSCs promoted
      rapid and greater bone regeneration during the entire observation period. In
      contrast, obvious mineralization was detected starting from 3 wks after
      implantation in the ADSC group. These results suggest that BMSCs might be more
      useful than ADSCs for rapid bone regeneration for sinus augmentation with
      simultaneous implant placement. 

PMID- 24097854
TI  - Translational genetics: advancing fronts for craniofacial health.
AB  - Scientific opportunities have never been better than today! The completion of the
      Human Genome project has sparked hope and optimism that cures for debilitating
      conditions can be achieved and tailored to individuals and communities. The
      availability of reference genome sequences and genetic variations as well as more
      precise correlations between genotype and phenotype have facilitated the progress
      made in finding solutions to clinical problems. While certain craniofacial and
      oral diseases previously deemed too difficult to tackle have benefited from basic
      science and technological advances over the past decade, there remains a critical
      need to translate the fruits of several decades' worth of basic and clinical
      research into tangible therapies that can benefit patients. The fifth Annual Fall
      Focused Symposium, "Translational Genetics - Advancing Fronts for Craniofacial
      Health", was created by the American Association for Dental Research (AADR) to
      foster its mission to advance interdisciplinary research that is directed toward
      improving oral health. The symposium showcased progress made in identifying
      molecular targets that are potential therapeutics for common and rare dental
      diseases and craniofacial disorders. Speakers focused on translational and
      clinical applications of their research and, where applicable, on strategies for
      new technologies and therapeutics. The critical needs to transfer new knowledge
      to the classroom and for further investment in the field were also emphasized.
      The symposium underscored the importance of basic research, chairside clinical
      observations, and population-based studies in driving the new translational
      connections needed for the development of cures for the most common and
      devastating diseases involving the craniofacial complex. 

PMID- 24097855
TI  - Micronutrients and oral clefts: a case-control study.
AB  - Little is known about oral clefts in developing countries. We aimed to identify
      micronutrient-related and environmental risk factors for oral clefts in Thailand.
      We tested hypotheses that maternal exposure during the periconceptional period to
      multivitamins or liver consumption would decrease cleft lip with or without cleft
      palate (CL +/- P) risk and that menstrual regulation supplements would increase
      CL +/- P risk. We conducted a multisite hospital-based case-control study in
      Thailand. We enrolled cases with CL +/- P and 2 live births as controls at birth
      from the same hospital. Mothers completed a questionnaire. Conditional logistic
      regression was used to estimate odds ratios (ORs) and 95% confidence intervals
      (CIs). Eighty-six cases and 172 controls were enrolled. Mothers who took a
      vitamin (adjusted OR, 0.39; 95% CI: 0.16, 0.94) or ate liver (adjusted OR, 0.26;
      95% CI: 0.12, 0.57) were less likely than those who did not to have an affected
      child. Mothers who took a menstrual regulation supplement were more likely than
      mothers who did not to have an affected child. Findings did not differ for
      infants with a family history of other anomalies or with isolated CL +/- P. If
      replicated, our finding that liver decreases CL +/- P risk could offer a low-cost
      primary prevention strategy. 

PMID- 24097857
TI  - Harnessing immune responses in the tumor microenvironment: all signals needed.
AB  - An agonist CD40 monoclonal antibody (CP-870,893), in combination with
      gemcitabine, is well tolerated in patients with advanced pancreatic
      adenocarcinoma. The combination results in induction of cytokines, B cell
      activation, and clinical responses. These findings support testing of
      immunotherapies in combination with other established and targeted therapies.

PMID- 24097856
TI  - Neutrophil homeostasis and periodontal health in children and adults.
AB  - This review summarizes the current state of knowledge on neutrophil basic biology
      and discusses how the breakdown of neutrophil homeostasis affects periodontal
      health. The homeostasis of neutrophils is tightly regulated through coordinated
      bone marrow production, release into the circulation, transmigration to and
      activation in peripheral tissues, and clearance of senescent neutrophils.
      Dysregulation of any of these homeostatic mechanisms at any age can cause severe
      periodontitis in humans and animal models. Accordingly, both impaired and
      excessive neutrophil activity (in terms of numbers or immune function) can
      precipitate periodontitis. Neutrophil defects of congenital origin (e.g.,
      congenital neutropenia, leukocyte adhesion deficiency, and Chediak-Higashi
      syndrome) are associated with cutaneous and systemic infections and early-onset
      forms of periodontitis affecting both the primary and permanent dentitions of
      children. However, the strong association between congenital neutrophil disorders
      and early-onset periodontitis is not currently adequately explained
      mechanistically. This suggests the operation of as-yet-unknown molecular
      mechanisms, although the available body of evidence leaves no doubt that
      neutrophils are integral to periodontal tissue homeostasis and health. 

PMID- 24097858
TI  - Test-firing ammunition for spliceosome inhibition in cancer.
AB  - E7107 is a derivative of the pladienolide family of natural product spliceosome
      inhibitors, which targets the U2 small nuclear ribonucleoprotein (snRNP) subunit
      SF3b. The results of a first-in-human trial with E7107 have been reported,
      representing an important translational step toward the goal of modulating RNA
      splicing for cancer therapy. Clin Cancer Res; 19(22); 6064-6. (c)2013 AACR. 

PMID- 24097859
TI  - It takes two to tango: Dual inhibition of PI3K and MAPK in rhabdomyosarcoma.
AB  - The PI3K/AKT/mTOR and RAS/RAF/MAPK pathways play essential roles in
      rhabdomyosarcoma. Singular targeting of each pathway is ineffective due to
      extensive cross-talk and compensatory feedback between these two pathways. Dual
      blockade with inhibitors of PI3K and MAPK in combination synergistically inhibits
      growth of rhabdomyosarcoma both in vitro and in vivo.

PMID- 24097860
TI  - Bendamustine and rituximab in relapsed and refractory hairy cell leukemia.
AB  - PURPOSE: To determine tolerability and for the first time explore efficacy of
      bendamustine-rituximab (BR) in multiply relapsed/refractory hairy cell leukemia
      (HCL), using two different dose levels of bendamustine. EXPERIMENTAL DESIGN:
      Patients with HCL with >=2 prior therapies requiring treatment received rituximab
      375 mg/m(2) days 1 and 15 plus bendamustine 70 (n = 6) or 90 (n = 6) mg/m(2),
      days 1 and 2, for six cycles at 4-week intervals. RESULTS: At 70 and 90
      mg/m(2)/dose of bendamustine, overall response rate was 100%, with three (50%)
      and four (67%) complete remissions (CR) in each respective group. Minimal
      residual disease (MRD) was absent in 67% and 100% of CRs, respectively. All six
      without MRD remain in CR at 30 to 35 (median, 31) months of follow-up. Soluble
      CD22 and CD25 levels decreased with all responses, with median values decreasing
      from 17.7 and 42 ng/mL at baseline to undetectable and 2 ng/mL after CR,
      respectively (P < 0.001). Of 12 patients receiving 72 cycles of BR, the most
      common toxicities were hematologic, including thrombocytopenia (83%), lymphopenia
      (75%), leukopenia (58%), and neutropenia (42%). Grade III and IV hematologic
      toxicity included lymphopenia and thrombocytopenia (each 75%), leukopenia (58%),
      and neutropenia (25%). No significant dose-related differences were detected in
      response or toxicity. CONCLUSION: BR has significant activity in HCL.
      Bendamustine at either 70 or 90 mg/m(2)/dose was highly effective in multiply
      relapsed/refractory HCL and could be considered for achieving durable CRs without
      MRD in patients after failure of standard therapies. As it was not dose-limiting,
      90 mg/m(2)/dose was chosen for future testing.

PMID- 24097861
TI  - Cabozantinib inhibits prostate cancer growth and prevents tumor-induced bone
      lesions.
AB  - PURPOSE: Cabozantinib, an orally available multityrosine kinase inhibitor with
      activity against mesenchymal epithelial transition factor (MET) and VEGF receptor
      2 (VEGFR2), induces resolution of bone scan lesions in men with castration
      resistant prostate cancer bone metastases. The purpose of this study was to
      determine whether cabozantinib elicited a direct antitumor effect, an indirect
      effect through modulating bone, or both. EXPERIMENTAL DESIGN: Using human
      prostate cancer xenograft studies in mice, we determined the impact of
      cabozantinib on tumor growth in soft tissue and bone. In vitro studies with
      cabozantinib were performed using (i) prostate cancer cell lines to evaluate its
      impact on cell growth, invasive ability, and MET and (ii) osteoblast cell lines
      to evaluate its impact on viability and differentiation and VEGFR2. RESULTS:
      Cabozantinib inhibited progression of multiple prostate cancer cell lines (Ace-1,
      C4-2B, and LuCaP 35) in bone metastatic and soft tissue murine models of prostate
      cancer, except for PC-3 prostate cancer cells in which it inhibited only
      subcutaneous growth. Cabozantinib directly inhibited prostate cancer cell
      viability and induced apoptosis in vitro and in vivo and inhibited cell invasion
      in vitro. Cabozantinib had a dose-dependent biphasic effect on osteoblast
      activity and inhibitory effect on osteoclast production in vitro that was
      reflected in vivo. It blocked MET and VEGFR2 phosphorylation in prostate cancer
      cells and osteoblast-like cells, respectively. CONCLUSION: These data indicate
      that cabozantinib has direct antitumor activity, and that its ability to modulate
      osteoblast activity may contribute to its antitumor efficacy.

PMID- 24097862
TI  - Semaphorin 4F as a critical regulator of neuroepithelial interactions and a
      biomarker of aggressive prostate cancer.
AB  - BACKGROUND: Semaphorin 4F (S4F) has roles in embryologic axon guidance and is
      expressed in adults. S4F is involved in cancer-induced neurogenesis. METHODS:
      Prostate cells were transfected with S4F retrovirus. Cells and controls were used
      for a bromodeoxyuridine (BrdUrd) incorporation assay (proliferation) and in vitro
      scratch and Matrigel Transwell chamber invasion assay (migration). Monoclonal
      antibodies were developed using baculovirus-expressed recombinant GST-S4F and
      used to immunostain tissue microarrays. Slides were imaged using deconvolution
      and analyzed using tissue segmentation. Data were correlated with
      clinicopathologic parameters, other biomarkers and survival analysis conducted.
      Heterogeneity of S4F expression was analyzed with unsupervised clustering
      algorithms. RESULTS: Proliferation rates measured by BrdUrd incorporation were
      higher in all S4F-transfected cells. S4F overexpression was associated with
      increased motility of the cancer cells. S4F expression was overexpressed in high
      grade prostatic intraepithelial neoplasia/prostate cancer than normal epithelium.
      S4F expression correlated with seminal vesicle invasion. Patients with high
      values of S4F in prostate cancer cytoplasm are at significantly higher risk of
      biochemical recurrence, by univariate and multivariate analyses. S4F cytoplasmic
      expression in prostate cancer cells also correlates with nerve density in
      prostate cancer and perineural invasion diameter. Correlations were identified
      with NF-kappaB and inversely with apoptosis in perineural invasion. CONCLUSION:
      These data show that S4F is significantly involved in human prostate cancer
      progression. S4F is a key regulator of the interactions between nerves in the
      tumor microenvironment and cancer cells. Because of the importance of cancer
      nerve interaction in the biology of cancer and its clinical implication, S4F can
      be considered a major therapeutic target. Clin Cancer Res; 19(22); 6101-11.
      (c)2013 AACR.

PMID- 24097863
TI  - A phase 1, dose-escalation, pharmacokinetic and pharmacodynamic study of BIIB021
      administered orally in patients with advanced solid tumors.
AB  - PURPOSE: BIIB021 is the first oral, synthetic, non-geldanamycin-based HSP90
      inhibitor that showed activity in preclinical models at low nanomolar
      concentrations. We performed a phase 1 trial of BIIB021 administered to subjects
      with advanced solid tumors. EXPERIMENTAL DESIGN: Sixty patients received BIIB021
      capsules orally on days 1, 4, 8, 11, 15, and 18 of each course in schedule 1, and
      on days 1, 4, 8, 11, 15, 18, 22, and 25 of each course in schedule 2. The
      treatment schedules were repeated every 28 days. In addition to determining the
      MTD, we evaluated pharmacokinetics of BIIB021 and pharmacodynamic effects of
      BIIB021 [Hsp70, HER2 extracellular domain (HER2-ECD)]. RESULTS: The MTD was 700
      mg twice weekly when BIIB021 was dosed for 3 weeks out of each 4-week course. The
      MTD for continuous dosing regimen was established at 600 mg twice weekly.
      Gastrointestinal (nausea, vomiting), hot flashes, and neurologic (dizziness)
      events characterize the safety profile of BIIB021 dosed twice weekly, with events
      mostly mild or moderate. Plasma exposure to BIIB021 was dose-dependent. Cmax
      occurred at approximately 90 minutes and t1/2 was approximately 1 hour across
      dosing cohorts of 25 to 800 mg BIIB021 twice weekly. The biologic activity of
      BIIB021 was demonstrated in serum, PBMCs, and tumor tissue. Hsp70 levels were
      increased (>150% from baseline) and serum HER2-ECD was significantly decreased
      (>15% inhibition from baseline). CONCLUSIONS: BIIB021 twice weekly, given with or
      without the 1 of 4-week rest period was tolerated in subjects with advanced solid
      tumors at doses that are pharmacodynamically active.

PMID- 24097864
TI  - Dual targeting of HER2-positive cancer with trastuzumab emtansine and pertuzumab:
      critical role for neuregulin blockade in antitumor response to combination
      therapy.
AB  - PURPOSE: Targeting HER2 with multiple HER2-directed therapies represents a
      promising area of treatment for HER2-positive cancers. We investigated combining
      the HER2-directed antibody-drug conjugate trastuzumab emtansine (T-DM1) with the
      HER2 dimerization inhibitor pertuzumab (Perjeta). EXPERIMENTAL DESIGN: Drug
      combination studies with T-DM1 and pertuzumab were performed on cultured tumor
      cells and in mouse xenograft models of HER2-amplified cancer. In patients with
      HER2-positive locally advanced or metastatic breast cancer (mBC), T-DM1 was dose
      escalated with a fixed standard pertuzumab dose in a 3+3 phase Ib/II study
      design. RESULTS: Treatment of HER2-overexpressing tumor cells in vitro with T-DM1
      plus pertuzumab resulted in synergistic inhibition of cell proliferation and
      induction of apoptotic cell death. The presence of the HER3 ligand, heregulin
      (NRG-1beta), reduced the cytotoxic activity of T-DM1 in a subset of breast cancer
      lines; this effect was reversed by the addition of pertuzumab. Results from mouse
      xenograft models showed enhanced antitumor efficacy with T-DM1 and pertuzumab
      resulting from the unique antitumor activities of each agent. In patients with
      mBC previously treated with trastuzumab, lapatinib, and chemotherapy, T-DM1 could
      be dosed at the maximum tolerated dose (MTD; 3.6 mg/kg every 3 weeks) with
      standard dose pertuzumab. Adverse events were mostly grade 1 and 2, with
      indications of clinical activity. CONCLUSIONS: Dual targeting of HER2 with the
      combination of T-DM1 and pertuzumab in cell culture and mouse xenograft models
      resulted in enhanced antitumor activity. In patients, this combination showed an
      encouraging safety and tolerability profile with preliminary evidence of
      efficacy.

PMID- 24097865
TI  - Effects of adjuvant chemoradiotherapy on the frequency and function of regulatory
      T cells in patients with head and neck cancer.
AB  - PURPOSE: Regulatory T cells (Treg) accumulate in tumor tissues and the peripheral
      blood of cancer patients and may persist after therapies. This cross-sectional
      study examines effects of adjuvant chemoradiotherapy (CRT) on Treg numbers and
      function in head and neck squamous cell carcinoma (HNSCC) patients. EXPERIMENTAL
      DESIGN: The frequency and absolute numbers of CD4(+), ATP-hydrolyzing
      CD4(+)CD39(+) and CD8(+) T cells, and expression levels of CD39, CD25, TGF-beta
      associated LAP and GARP on Treg were measured by flow cytometry in 40 healthy
      donors (NC) and 71 HNSCC patients [29 untreated with active disease (AD); 22
      treated with surgery; 20 treated with CRT]. All treated subjects had no evident
      disease (NED) at the time of phlebotomy. In an additional cohort of 40 subjects
      with AD (n = 15), NED (n = 10), and NC (n = 15), in vitro sensitivity of CD4(+) T
      cell subsets to cisplatin and activation-induced cell death (AICD) was tested in
      Annexin V-binding assays. RESULTS: CRT decreased the frequency of circulating
      CD4(+) T cells (P < 0.002) but increased that of CD4(+)CD39(+) Treg (P <= 0.001)
      compared with untreated or surgery-only patients. Treg frequency remained
      elevated for >3 years. CRT increased surface expression of LAP, GARP, and CD39 on
      Treg. In vitro Treg were resistant to AICD or cisplatin but conventional CD4(+) T
      cells (Tconv) were not. CRT-induced Treg from AD or NC subjects upregulated
      prosurvival proteins whereas Tconv upregulated proapoptotic Bax. CONCLUSIONS:
      Highly suppressive, cisplatin-resistant Treg increase in frequency and persist
      after CRT and could be responsible for suppression of antitumor immune responses
      and recurrence in HNSCC.

PMID- 24097866
TI  - A phase I trial of imetelstat in children with refractory or recurrent solid
      tumors: a Children's Oncology Group Phase I Consortium Study (ADVL1112).
AB  - PURPOSE: Imetelstat is a covalently-lipidated 13-mer thiophosphoramidate
      oligonucleotide that acts as a potent specific inhibitor of telomerase. It binds
      with high affinity to the template region of the RNA component of human
      telomerase (hTERC) and is a competitive inhibitor of telomerase enzymatic
      activity. The purpose of this study was to determine the recommended phase II
      dose of imetelstat in children with recurrent or refractory solid tumors.
      EXPERIMENTAL DESIGN: Imetelstat was administered intravenously more than two
      hours on days 1 and 8, every 21 days. Dose levels of 225, 285, and 360 mg/m(2)
      were evaluated, using the rolling-six design. Imetelstat pharmacokinetic and
      correlative biology studies were also performed during the first cycle. RESULTS:
      Twenty subjects were enrolled (median age, 14 years; range, 3-21). Seventeen were
      evaluable for toxicity. The most common toxicities were neutropenia,
      thrombocytopenia, and lymphopenia, with dose-limiting myelosuppression in 2 of 6
      patients at 360 mg/m(2). Pharmacokinetics is dose dependent with a lower
      clearance at the highest dose level. Telomerase inhibition was observed in
      peripheral blood mononuclear cells at 285 and 360 mg/m(2). Two confirmed partial
      responses, osteosarcoma (n = 1) and Ewing sarcoma (n = 1), were observed.
      CONCLUSIONS: The recommended phase II dose of imetelstat given on days 1 and 8 of
      a 21-day cycle is 285 mg/m(2).

PMID- 24097868
TI  - Ang-2-VEGF-A CrossMab, a novel bispecific human IgG1 antibody blocking VEGF-A and
      Ang-2 functions simultaneously, mediates potent antitumor, antiangiogenic, and
      antimetastatic efficacy.
AB  - PURPOSE: VEGF-A blockade has been clinically validated as a treatment for human
      cancers. Angiopoietin-2 (Ang-2) expression has been shown to function as a key
      regulator of tumor angiogenesis and metastasis. EXPERIMENTAL DESIGN: We have
      applied the recently developed CrossMab technology for the generation of a
      bispecific antibody recognizing VEGF-A with one arm based on bevacizumab
      (Avastin), and the other arm recognizing Ang-2 based on LC06, an Ang-2 selective
      human IgG1 antibody. The potency of Ang-2-VEGF CrossMab was evaluated alone and
      in combination with chemotherapy using orthotopic and subcutaneous
      xenotransplantations, along with metastasis analysis by quantitative real-time
      Alu-PCR and ex vivo evaluation of vessels, hypoxia, proliferation, and apoptosis.
      The mechanism of action was further elucidated using Western blotting and ELISA
      assays. RESULTS: Ang-2-VEGF-A CrossMab showed potent tumor growth inhibition in a
      panel of orthotopic and subcutaneous syngeneic mouse tumors and patient or cell
      line-derived human tumor xenografts, especially at later stages of tumor
      development. Ang-2-VEGF-A CrossMab treatment led to a strong inhibition of
      angiogenesis and an enhanced vessel maturation phenotype. Neoadjuvant combination
      with chemotherapy resulted in complete tumor regression in primary tumor-bearing
      Ang-2-VEGF-A CrossMab-treated mice. In contrast to Ang-1 inhibition, anti-Ang-2
      VEGF-A treatment did not aggravate the adverse effect of anti-VEGF treatment on
      physiologic vessels. Moreover, treatment with Ang-2-VEGF-A CrossMab resulted in
      inhibition of hematogenous spread of tumor cells to other organs and reduced
      micrometastatic growth in the adjuvant setting. CONCLUSION: These data establish
      Ang-2-VEGF-A CrossMab as a promising antitumor, antiangiogenic, and
      antimetastatic agent for the treatment of cancer.

PMID- 24097867
TI  - Phase I study of panobinostat plus everolimus in patients with relapsed or
      refractory lymphoma.
AB  - PURPOSE: To evaluate the safety and efficacy of panobinostat plus everolimus in
      patients with relapsed Hodgkin and non-Hodgkin lymphoma. The concept was
      supported by the single-agent clinical activity of histone deacetylase inhibitors
      and mTOR inhibitors, and on the in vitro mechanism-based synergistic
      antiproliferative activity. EXPERIMENTAL DESIGN: This was a phase I study in
      patients with relapsed or refractory Hodgkin and non-Hodgkin lymphoma using
      panobinostat orally on Monday/Wednesday/Friday and everolimus orally daily.
      Toxicity and responses were assessed in dose-escalation cohort followed by
      expansion cohort at maximum-tolerated dose. Exploratory analysis of serum
      cytokine levels was performed. RESULTS: Thirty patients were enrolled onto four
      dose levels. The dose-limiting toxicity was thrombocytopenia. The maximal
      tolerated dose was panobinostat 20 mg and everolimus 10 mg. Grade 3/4 toxicity
      included thrombocytopenia (64%), neutropenia (47%), anemia (20%), infection
      (10%), fatigue (7%), and dyspnea (7%). A total of 10 patients (33%; indolent
      lymphoma, T-cell lymphoma, mantle cell lymphoma, and Hodgkin lymphoma) achieved
      objective responses. In patients with Hodgkin lymphoma (n = 14), the overall
      response rate was 43% with complete response rate of 15%. In patients with
      Hodgkin lymphoma, multiple serum cytokine levels decreased significantly after
      treatment with this combination therapy. Of note, clinical responses were
      associated with a decrease in serum interleukin-5 levels (day 8, P = 0.013, and
      day 15, P = 0.021). CONCLUSIONS: Our data suggest that the combination therapy is
      active but with significant thrombocytopenia. Future studies should explore
      alternate scheduling and different compounds that target the same pathways to
      improve the tolerability of this novel combination.

PMID- 24097869
TI  - Loss of NAPRT1 expression by tumor-specific promoter methylation provides a novel
      predictive biomarker for NAMPT inhibitors.
AB  - PURPOSE: We sought to identify predictive biomarkers for a novel nicotinamide
      phosphoribosyltransferase (NAMPT) inhibitor. EXPERIMENTAL DESIGN: We use a NAMPT
      inhibitor, GNE-617, to evaluate nicotinic acid rescue status in a panel of more
      than 400 cancer cell lines. Using correlative analysis and RNA interference
      (RNAi), we identify a specific biomarker for nicotinic acid rescue status. We
      next determine the mechanism of regulation of expression of the biomarker.
      Finally, we develop immunohistochemical (IHC) and DNA methylation assays and
      evaluate cancer tissue for prevalence of the biomarker across indications.
      RESULTS: Nicotinate phosphoribosyltransferase (NAPRT1) is necessary for nicotinic
      acid rescue and its expression is the major determinant of rescue status. We
      demonstrate that NAPRT1 promoter methylation accounts for NAPRT1 deficiency in
      cancer cells, and NAPRT1 methylation is predictive of rescue status in cancer
      cell lines. Bisulfite next-generation sequencing mapping of the NAPRT1 promoter
      identified tumor-specific sites of NAPRT1 DNA methylation and enabled the
      development of a quantitative methylation-specific PCR (QMSP) assay suitable for
      use on archival formalin-fixed paraffin-embedded tumor tissue. CONCLUSIONS: Tumor
      specific promoter hypermethylation of NAPRT1 inactivates one of two NAD salvage
      pathways, resulting in synthetic lethality with the coadministration of a NAMPT
      inhibitor. NAPRT1 expression is lost due to promoter hypermethylation in most
      cancer types evaluated at frequencies ranging from 5% to 65%. NAPRT1-specific
      immunohistochemical or DNA methylation assays can be used on archival formalin
      paraffin-embedded cancer tissue to identify patients likely to benefit from
      coadministration of a Nampt inhibitor and nicotinic acid.

PMID- 24097870
TI  - EZH2 protein expression associates with the early pathogenesis, tumor
      progression, and prognosis of non-small cell lung carcinoma.
AB  - PURPOSE: Enhancer of zeste homolog 2 (EZH2) promotes carcinogenesis by
      epigenetically silencing tumor suppressor genes. We studied EZH2 expression by
      immunohistochemistry in a large series of non-small cell lung carcinomas (NSCLC)
      in association with tumor characteristics and patient outcomes. EXPERIMENTAL
      DESIGN: EZH2 immunohistochemistry expression was analyzed in 265 normal and
      premalignant bronchial epithelia, 541 primary NSCLCs [221 squamous cell
      carcinomas (SCC) and 320 adenocarcinomas] and 36 NSCLCs with paired brain
      metastases. An independent set of 91 adenocarcinomas was also examined. EZH2
      expression was statistically correlated with clinico-pathological information,
      and EGFR/KRAS mutation status. RESULTS: EZH2 expression was significantly (P <
      0.0001) higher in SCCs compared with adenocarcinomas and in brain metastasis
      relative to matched primary tumors (P = 0.0013). EZH2 expression was
      significantly (P < 0.0001) elevated in bronchial preneoplastic lesions with
      increasing severity. In adenocarcinomas, higher EZH2 expression significantly
      correlated with younger age, cigarette smoking, and higher TNM stage (P = 0.02 to
      P < 0.0001). Higher EZH2 expression in adenocarcinoma was associated with worse
      recurrence-free survival (RFS; P = 0.025; HR = 1.54) and overall survival (OS; P
      = 0.0002; HR = 1.96). Furthermore, lung adenocarcinomas with low EZH2 levels and
      high expression of the lineage-specific transcription factor, TTF-1, exhibited
      significantly improved RFS (P = 0.009; HR = 0.51) and OS (P = 0.0011; HR = 0.45),
      which was confirmed in the independent set of 91 adenocarcinomas. CONCLUSION: In
      lung, EZH2 expression is involved in early pathogenesis of SCC and correlates
      with a more aggressive tumor behavior of adenocarcinoma. When EZH2 and TTF-1
      expressions are considered together, they serve as a prognostic marker in
      patients with surgically resected lung adenocarcinomas.

PMID- 24097871
TI  - Contrasting expression patterns of histone mRNA and microRNA 760 in patients with
      gastric cancer.
AB  - PURPOSE: Recent studies revealed that both disseminated tumor cells and
      noncancerous cells contributed to cancer progression cooperatively in the bone
      marrow. Here, RNA-seq analysis of bone marrow from gastric cancer patients was
      performed to identify prognostic markers for gastric cancer. EXPERIMENTAL DESIGN:
      Bone marrow samples from eight gastric cancer patients (stages I and IV: n = 4
      each) were used for RNA-seq analysis. Results were validated through quantitative
      real-time PCR (qRT-PCR) analysis of HIST1H3D expression in 175 bone marrow, 92
      peripheral blood, and 115 primary tumor samples from gastric cancer patients. miR
      760 expression was assayed using qRT-PCR in 105 bone marrow and 96 primary tumor
      samples. Luciferase reporter assays were performed to confirm whether histone
      mRNAs were direct targets of miR-760. miR-760 expression was also evaluated in
      noncancerous cells from gastric cancer patients. RESULTS: RNA-seq analysis of
      bone marrow samples from gastric cancer patients revealed higher expression of
      multiple histone mRNAs in stage IV patients. HIST1H3D expression in the bone
      marrow, peripheral blood, and primary tumor of stage IV patients was higher than
      that in stage I patients (P = 0.0284, 0.0243, and 0.0006, respectively). In
      contrast, miR-760 was downregulated in the bone marrow and primary tumor of stage
      IV patients compared with stage I patients (P = 0.0094 and 0.0018, respectively).
      Histone mRNA and miR-760 interacted directly. Furthermore, miR-760 was
      downregulated in noncancerous mucosa in stage IV gastric cancer patients.
      CONCLUSION: Histone mRNA was upregulated, whereas miR-760 was downregulated in
      the bone marrow and primary tumor of advanced gastric cancer patients, suggesting
      that the histone mRNA/miR-760 axis had a crucial role in the development of
      gastric cancer.

PMID- 24097872
TI  - A novel engineered anti-CD20 tracer enables early time PET imaging in a humanized
      transgenic mouse model of B-cell non-Hodgkins lymphoma.
AB  - PURPOSE: The aim of this article was to evaluate the use of a novel engineered
      anti-CD20 protein based on the 10 kDa human fibronectin type 3 domain (FN3) and
      subsequently compare with (64)Cu-rituximab for positron emission tomography (PET)
      imaging of CD20. EXPERIMENTAL DESIGN: The engineered FN3(CD20) and FN3(WT) were
      produced in Escherichia coli cells at 2 to 5 mg/L, conjugated to DOTA, labeled
      with (64)Cu, and used for PET imaging of huCD20 expression in B cells. Humanized
      transgenic mice and subcutaneously xenografted mice each received intravenous
      (64)Cu-FN3(CD20) or FN3(WT) (3.7 MBq/4 MUg Do-FN3 in 200 MUL PBS). Control group
      received a blocking dose (50-fold excess) of unconjugated FN3(CD20) two hours
      before radiotracer injection. PET imaging was carried out at 1 to 24 hours
      postinjections. RESULTS: In vitro assay demonstrated FN3 binds CD20 with 20
      nmol/L affinity on CD20-expressing cells. (64)Cu-FN3(CD20) showed clear, high
      contrast visualization of huCD20-expressing B cells in the spleen of transgenic
      mice as early as 1 hour postinjection [38 +/- 3% injected dose (ID)/g] and
      exhibited a spleen-to-blood ratio of 13 by 4 hours. This is higher uptake (P =
      0.04) and 10-fold greater signal-to-background (P = 0.04) than the (64)Cu
      rituximab antibody radiotracer. Tumor uptake (16.8 +/- 1.6 vs. 5.6 +/- 1.4%ID/g)
      and tumor:background ratios were superior for FN3CD20 relative to rituximab in
      xenograft studies as well. CONCLUSIONS: The (64)Cu-Do-FN3(CD20) radiotracer
      represents a novel small, high-affinity binder for imaging human CD20, which may
      be well suited for B-cell non-Hodgkin's lymphoma imaging in patients at early
      time points.

PMID- 24097875
TI  - BVA President highlights concerns about OV tendering.

PMID- 24097873
TI  - Prognostic and predictive blood-based biomarkers in patients with advanced
      pancreatic cancer: results from CALGB80303 (Alliance).
AB  - PURPOSE: CALGB80303 was a phase III trial of 602 patients with locally advanced
      or metastatic pancreatic cancer comparing gemcitabine/bevacizumab versus
      gemcitabine/placebo. The study found no benefit in any outcome from the addition
      of bevacizumab to gemcitabine. Blood samples were collected and multiple
      angiogenic factors were evaluated and then correlated with clinical outcome in
      general (prognostic markers) and with benefit specifically from bevacizumab
      treatment (predictive markers). EXPERIMENTAL DESIGN: Plasma samples were analyzed
      via a novel multiplex ELISA platform for 31 factors related to tumor growth,
      angiogenesis, and inflammation. Baseline values for these factors were correlated
      with overall survival (OS) using univariate Cox proportional hazard regression
      models and multivariable Cox regression models with leave-one-out cross
      validation. Predictive markers were identified using a treatment by marker
      interaction term in the Cox model. RESULTS: Baseline plasma was available from
      328 patients. Univariate prognostic markers for OS were identified including:
      Ang2, CRP, ICAM-1, IGFBP-1, TSP-2 (all P < 0.001). These prognostic factors were
      found to be highly significant, even after adjustment for known clinical factors.
      Additional modeling approaches yielded prognostic signatures from multivariable
      Cox regression. The gemcitabine/bevacizumab signature consisted of IGFBP-1,
      interleukin-6, PDGF-AA, PDGF-BB, TSP-2; whereas the gemcitabine/placebo signature
      consisted of CRP, IGFBP-1, PAI-1, PDGF-AA, P-selectin (both P < 0.0001). Finally,
      three potential predictive markers of bevacizumab efficacy were identified: VEGF
      D (P < 0.01), SDF1 (P < 0.05), and Ang2 (P < 0.05). CONCLUSION: This study
      identified strong prognostic markers for pancreatic cancer patients. Predictive
      marker analysis indicated that plasma levels of VEGF-D, Ang2, and SDF1
      significantly predicted for benefit or lack of benefit from bevacizumab in this
      population.

PMID- 24097876
TI  - Veterinary input vital, says secretary of state.

PMID- 24097881
TI  - Veterinary medicines: product update.
AB  - The following information has been produced for Veterinary Record by the
      Veterinary Medicines Directorate (VMD) to provide an update for veterinary
      surgeons on recent changes to marketing authorisations for veterinary medicines
      in the UK and on other relevant issues.

PMID- 24097874
TI  - Interleukin-7 mediates selective expansion of tumor-redirected cytotoxic T
      lymphocytes (CTLs) without enhancement of regulatory T-cell inhibition.
AB  - PURPOSE: The antitumor activity of chimeric antigen receptor (CAR)-redirected
      CTLs should be enhanced if it were possible to increase their proliferation and
      function after adoptive transfer without concomitantly increasing the
      proliferation and function of regulatory T cells (Treg). Here, we explored
      whether the lack of IL-7Ralpha in Treg can be exploited by the targeted
      manipulation of the interleukin-7 (IL-7) cytokine-cytokine receptor axis in CAR
      engrafted Epstein-Barr Virus-specific CTLs (EBV-CTLs) to selectively augment
      their growth and antitumor activity even in the presence of Treg. EXPERIMENTAL
      DESIGN: We generated a bicistronic retroviral vector encoding a GD2-specific CAR
      and the IL-7Ralpha subunit, expressed the genes in EBV-CTLs, and assessed their
      capacity to control tumor growth in the presence of Treg in vitro and in vivo
      when exposed to either interleukin-2 (IL-2) or IL-7 in a neuroblastoma xenograft.
      RESULTS: We found that IL-7, in sharp contrast with IL-2, supports the
      proliferation and antitumor activity of IL-7Ralpha.CAR-GD2(+) EBV-CTLs both in
      vitro and in vivo even in the presence of fully functional Treg. CONCLUSIONS: IL
      7 selectively favors the survival, proliferation, and effector function of IL
      7Ralpha-transgenic/CAR-redirected EBV-CTLs in the presence of Treg both in vitro
      and in vivo. Thus, IL-7 can have a significant impact in sustaining expansion and
      persistence of adoptively CAR-redirected CTLs.

PMID- 24097882
TI  - Ostertagiosis causes illthrift and death in older cattle.
AB  - Ostertagiosis diagnosed in a six-year-old suckler cow. Congenital ear deformities
      seen in several Ayrshire-cross calves. Border disease virus infection associated
      with numerous neonatal lamb deaths. Coccidiosis, PCV-2 and hepatosis dietetica
      implicated in piglet deaths. Spinal aspergillosis suspected in pheasant poults
      with lameness and paralysis. These are among matters discussed in the disease
      surveillance report for July from SAC Consulting: Veterinary Services (SAC C VS).

PMID- 24097883
TI  - Dairy production: maintaining the focus on mastitis prevention.

PMID- 24097884
TI  - Switching between medications for the management of epilepsy in dogs.

PMID- 24097885
TI  - Support for poultry disease research.

PMID- 24097894
TI  - False biomarker discovery due to reactivity of a commercial ELISA for CUZD1 with
      cancer antigen CA125.
AB  - BACKGROUND: By using proteomics and bioinformatics, we have previously identified
      a group of highly pancreas-specific proteins as candidate pancreatic ductal
      adenocarcinoma (PDAC) biomarkers. With the use of commercially available ELISAs,
      the performance of some of these candidates was initially evaluated in a
      relatively small serum cohort (n = 100 samples). This phase revealed that CUB and
      zona pellucida-like domains protein 1 (CUZD1) may represent a new, promising PDAC
      biomarker. METHODS: We performed detailed experiments to investigate the
      specificity of the commercial CUZD1 ELISA assay. CUZD1 was expressed in house in
      both bacteria and yeast expression systems. Recombinant CUZD1 and biological
      samples containing CUZD1, as well as commercial CUZD1 ELISA standards, were
      analyzed by Western blot, size exclusion HPLC, and mass spectrometry (LC-MS
      Orbitrap). RESULTS: We confirmed that instead of CUZD1, the commercial assay is
      recognizing a nonhomologous, known cancer antigen [cancer antigen 125 (CA125)].
      CONCLUSIONS: We conclude that poor characterization of commercial ELISA assays is
      a factor that could lead to false biomarker discovery. To our knowledge, this is
      the first report documenting that a commercial ELISA marketed for one analyte
      (CUZD1) may, in fact, recognize a different, nonhomologous antigen (CA125).

PMID- 24097899
TI  - DNA damage responses in prokaryotes: regulating gene expression, modulating
      growth patterns, and manipulating replication forks.
AB  - Recent advances in the area of bacterial DNA damage responses are reviewed here.
      The SOS pathway is still the major paradigm of bacterial DNA damage response, and
      recent studies have clarified the mechanisms of SOS induction and key
      physiological roles of SOS including a very major role in genetic exchange and
      variation. When considering diverse bacteria, it is clear that SOS is not a
      uniform pathway with one purpose, but rather a platform that has evolved for
      differing functions in different bacteria. Relating in part to the SOS response,
      the field has uncovered multiple apparent cell-cycle checkpoints that assist cell
      survival after DNA damage and remarkable pathways that induce programmed cell
      death in bacteria. Bacterial DNA damage responses are also much broader than SOS,
      and several important examples of LexA-independent regulation will be reviewed.
      Finally, some recent advances that relate to the replication and repair of
      damaged DNA will be summarized. 

PMID- 24097901
TI  - Echoes of a distant past: The cag pathogenicity island of Helicobacter pylori.
AB  - This review discusses the multiple roles of the CagA protein encoded by the cag
      pathogenicity island of Helicobacter pylori and highlights the CagA degradation
      activities on p53. By subverting the p53 tumor suppressor pathway CagA induces a
      strong antiapoptotic effect. Helicobacter pylori infection has been always
      associated with an increased risk of gastric cancer. The pro-oncogenic functions
      of CagA also target the tumor suppressor ASPP2. In the absence of tumor
      suppressor genes, cells survive and proliferate at times and in places where
      their survival and proliferation are inappropriate.

PMID- 24097902
TI  - Metabolism and disposition of oral dabrafenib in cancer patients: proposed
      participation of aryl nitrogen in carbon-carbon bond cleavage via decarboxylation
      following enzymatic oxidation.
AB  - A phase I study was conducted to assess the metabolism and excretion of
      [(14)C]dabrafenib (GSK2118436; N-{3-[5-(2-amino-4-pyrimidinyl)-2-(1,1
      dimethylethyl)-1,3-thiazol-4-yl]-2-fluorophenyl}-2,6-difluorobenzene sulfonamide,
      methanesulfonate salt), a BRAF inhibitor, in four patients with BRAF V600
      mutation-positive tumors after a single oral dose of 95 mg (80 uCi). Assessments
      included the following: 1) plasma concentrations of dabrafenib and metabolites
      using validated ultra-high-performance liquid chromatography--tandem mass
      spectrometry methods, 2) plasma and blood radioactivity, 3) urinary and fecal
      radioactivity, and 4) metabolite profiling. Results showed the mean total
      recovery of radioactivity was 93.8%, with the majority recovered in feces (71.1%
      of administered dose). Urinary excretion accounted for 22.7% of the dose, with no
      detection of parent drug in urine. Dabrafenib is metabolized primarily via
      oxidation of the t-butyl group to form hydroxy-dabrafenib. Hydroxy-dabrafenib
      undergoes further oxidation to carboxy-dabrafenib, which subsequently converts to
      desmethyl-dabrafenib via a pH-dependent decarboxylation. The half-lives for
      carboxy- and desmethyl-dabrafenib were longer than for parent and hydroxy
      dabrafenib (18-20 vs. 5-6 hours). Based on area under the plasma concentration
      time curve, dabrafenib, hydroxy-, carboxy-, and desmethyl-dabrafenib accounted
      for 11%, 8%, 54%, and 3% of the plasma radioactivity, respectively. These results
      demonstrate that the major route of elimination of dabrafenib is via oxidative
      metabolism (48% of the dose) and biliary excretion. Based on our understanding of
      the decarboxylation of carboxy-dabrafenib, a low pH-driven, nonenzymatic
      mechanism involving participation of the aryl nitrogen is proposed to allow
      prediction of metabolic oxidation and decarboxylation of drugs containing an aryl
      nitrogen positioned alpha to an alkyl (ethyl or t-butyl) side chain.

PMID- 24097903
TI  - Commentary on Canadian child maltreatment data.
AB  - The issue of how to best collect child maltreatment data is a key concern within
      the Public Health Agency of Canada (PHAC). We argue that maltreatment data can be
      collected from children, adolescents, and parents with approaches that are
      accurate, methodologically robust, legal, and ethical. It has been done in other
      countries. First, we clarify ongoing child maltreatment data collection by the
      Canadian government and address PHAC initiatives to include child maltreatment
      questions in national contemporaneous surveys. Second, we identify examples of
      population-based studies with child, adolescent, and parent respondents. Third,
      we highlight some measurement considerations. Fourth, we address ethical
      considerations in conducting this type of research. 

PMID- 24097900
TI  - Repair of strand breaks by homologous recombination.
AB  - In this review, we discuss the repair of DNA double-strand breaks (DSBs) using a
      homologous DNA sequence (i.e., homologous recombination [HR]), focusing mainly on
      yeast and mammals. We provide a historical context for the current view of HR and
      describe how DSBs are processed during HR as well as interactions with other DSB
      repair pathways. We discuss the enzymology of the process, followed by studies on
      DSB repair in living cells. Whenever possible, we cite both original articles and
      reviews to aid the reader for further studies. 

PMID- 24097904
TI  - Police reporting practices for sexual assault cases in which "the victim does not
      wish to pursue charges".
AB  - Prior research examining sexual assault case attrition has focused on the
      processing of cases across the justice system. Studies have examined arrest
      decision making and prosecutorial decision making in an attempt to better
      understand where and when cases drop out of the system. Less explored are police
      reporting practices during the initial stage of processing for cases in which the
      officer stated that the victim chose to drop her case. We addressed this gap in
      the literature by reviewing law enforcement incident reports at their onset,
      specifically; we examine reports of cases in which the officer reported the
      victim chose to drop the case. Results indicated that of the 125 cases of sexual
      assault reported to the police, 41 reports (32.8%) stated that the victim decided
      to no longer pursue charges. However, few police reports (30.2%) provided a clear
      rationale for why the victim decided to no longer pursue charges. Results of this
      study call for more standardized police reporting practices and point to the need
      for future research into the initial stage of law enforcement involvement in
      adult sexual assault cases. 

PMID- 24097905
TI  - Why are crime victims at risk of being victimized again? Substance use,
      depression, and offending as mediators of the victimization-revictimization link.
AB  - Using three waves of data from 5,165 male and 5,924 female teenagers surveyed in
      the National Longitudinal Study of Adolescent Health, this study tested whether
      drug use, alcohol use, depression, and offending mediate the link between a
      serious violent criminal victimization and a subsequent serious violent
      revictimization. Results indicated that victimization at Wave 1 significantly
      predicted changes in violent offending, delinquency, and drug use at Wave 2, even
      controlling for all other lagged mediators. Violent offending emerged as a robust
      and consistent mediator of the victimization-revictimization link for males. For
      females, all the mediators together produced a significant and large indirect
      effect that reduced the direct effect of prior victimization to nonsignificance,
      but no one single mediator was significant. This study demonstrates that
      revictimization is partially the result of behavioral changes following
      victimization. The fact that mediation between victimization and revictimization
      occurred through a cluster of changed behaviors and moods suggests that the
      impact of victimization is greater for females than males. This evidence that
      victimization changes behavior and increases risks and that these risks differ by
      gender has implications for both mental health care and law enforcement. 

PMID- 24097906
TI  - Predicting sexual assault kit submission among adolescent rape cases treated in
      forensic nurse examiner programs.
AB  - Following a sexual assault, victims are usually advised to have a medical
      forensic exam and sexual assault forensic exam kit (SAK). Once completed, the SAK
      is to be transported by law enforcement to the crime lab for analysis. However,
      many kits are never transported to the crime lab, thereby preventing forensic
      evidence obtained in the kit to be used during the prosecutorial process. The
      current study examined rates of SAK submission for 393 adolescent sexual assault
      cases in two Midwestern communities and explored what factors predicted law
      enforcement officers' submission of SAKs to the crime lab for analysis. Findings
      reveal that more than 40% of the adolescent cases did not have their SAK
      submitted, and several factors, including the age and race of the victim, the
      number of perpetrators in the assault, and the number of assaultive acts,
      predicted SAK submission. Implications for SAK community protocols are discussed.

PMID- 24097908
TI  - Non-fatal gunshot trauma among a sample of adolescents in Djibouti: prevalence
      and sociodemographic associations.
AB  - Firearm trauma is the second most common cause of serious injury among
      adolescents in the Republic of Djibouti. The aim of this study was to explore the
      sociodemographic correlates of serious injury and non-fatal gunshot trauma among
      adolescents in Djibouti. Using multinomial logistic regression, we compared a
      sample of adolescents (N = 1,711) who self-reported a non-firearm-related serious
      injury (n = 587) and those who reported a firearm-related injury (n = 101) with
      non-injured participants (n = 1,023) during a 12-month recall period. Analyses
      targeted demographic, behavioral, social, mental health, and family factors.
      After adjusting for covariates, participants reporting a non-firearm-related
      serious injury were more likely to report having been involved in physical fights
      (relative risk ratio [RRR] = 145; confidence interval [CI] = [1.04, 2.02), being
      bullied (RRR = 2.83; CI = [2.24, 3.56]), feeling lonely (RRR = 1.48; CI = [1.11,
      1.96]), having signs of depression (RRR = 1.27; CI = [1.02, 1.58]), and be truant
      from school (RRR = 1.68; CI = [1.25, 2.28]). Those who reported a gunshot injury
      recorded being bullied (RRR = 2.83; CI = [1.77, 4.53]) and physically attacked at
      higher rates (RRR = 1.78; CI = [1.09, 2.89]). Serious injuries, whether firearm
      related or not, are important threats to adolescent health in Djibouti with
      potentially serious health-related correlates. More research, particularly
      multilevel designs, are needed to explain context-relevant factors associated
      with serious trauma in Djibouti. 

PMID- 24097907
TI  - Exposure to family violence and attachment styles as predictors of dating
      violence perpetration among men and women: a mediational model.
AB  - This study examined a multiple mediator model explaining how sibling perpetration
      and one's attachment style mediate the relation between parent-to-child
      victimization and dating violence perpetration. A sample of undergraduate
      students (n = 392 women, n = 89 men) completed measures of the aforementioned
      variables on an Internet survey. For men, path analyses found no mediation;
      parent-to-child victimization had a direct association with dating violence
      perpetration, no association was found between sibling perpetration and dating
      violence perpetration, and attachment anxiety, but not attachment avoidance, was
      positively associated with dating violence perpetration for men. For women, the
      hypothesized mediation model was supported; parent-to-child victimization had a
      direct association with dating violence perpetration, and sibling perpetration
      and attachment anxiety served as mediating variables. Attachment avoidance was
      not associated with dating violence perpetration for women. Implications for
      future research and clinical practice are discussed. 

PMID- 24097909
TI  - To act or not to act, that is the question? Barriers and facilitators of
      bystander intervention.
AB  - A promising line of inquiry in sexual violence prevention involves training
      potential bystanders to intervene in situations where there is risk for violence.
      Theories of bystander intervention often discuss barriers to helping behavior,
      but there has been little empirical inquiry into this question. We will present
      findings of a study of both barriers and facilitators of helping behavior in the
      context of sexual violence among first-semester college students. Two hundred and
      forty-two first year college students completed surveys during their first year
      of college. Measures included assessment of bystander behavior, perceived
      barriers to helping, as well as a variety of other variables identified in the
      literature as key correlates of helping. Quantitative and qualitative analyses
      were used to (a) describe barriers and facilitators of helping, (b) examine the
      relationship between barriers and self-reports of helping, and (c) model
      individual differences in helping behavior. In quantitative analyses, barriers,
      as assessed in this study, were better predictors of helping behavior directed at
      strangers than helping of friends. Results suggested that open-ended responses
      about the facilitators and barriers to helping for sexual violence map well onto
      social-psychological models of bystander behavior, and that greater prosocial
      tendencies, an intrapersonal variable, increase actual helping behavior. A more
      specific understanding of what promotes and hinders helping can be used to
      enhance prevention education efforts focused on increasing helpful bystander
      actions. 

PMID- 24097910
TI  - Motivational attributions about intimate partner violence among male and female
      perpetrators.
AB  - Given the widely acknowledged negative impact and pervasiveness of intimate
      partner violence (IPV), many have sought to discover why people perpetrate IPV.
      To this end, IPV risk factors have been extensively studied and attributions have
      recently received more attention. Evidence suggests males and females have
      similar attributions and both engage in IPV. Yet, IPV tactics and attribution
      rates appear to differ by perpetrator sex. This study explores whether males and
      females tend to attribute different reasons to their IPV, and whether these
      attributions help to distinguish among physical and psychological IPV tactics.
      The study tests three hypotheses: that IPV tactics and attributions will differ
      between females and males, that females and males will have similar latent
      constructs associated with types of attributions made about IPV, and that males
      and females will have different relationships among attribution factors and IPV
      tactics. This study is based on a cross-sectional survey of 5,035 18- to 25-year
      old undergraduate university students in the Southeastern United States. Analyses
      used SPSS 20 to conduct basic and bivariate analyses, multiway frequency
      analysis, reliability analysis, and logistic regression, and MPlus 6.12 to
      conduct exploratory and confirmatory factor analysis. Overall, the results
      provide support for the three study hypotheses, although there was inconsistency
      in findings for the second hypothesis. The results suggest important practice and
      research implications, which are discussed. The study fills a gap in the limited
      literature on IPV perpetrator motivational attributions by presenting a nuanced
      analysis of an early measure of IPV attributions. 

PMID- 24097911
TI  - Women's autonomy and experience of physical violence within marriage in rural
      India: evidence from a prospective study.
AB  - Evidence regarding the relationship between married women's autonomy and risk of
      marital violence remains mixed. Moreover, studies examining the contribution of
      specific aspects of women's autonomy in influencing the risk of marital violence
      using measures of autonomy that incorporate its dynamic nature are rare. We
      investigated the relationship between women's autonomy and their experience of
      marital violence in rural India using prospective data. We used data on 4,904
      rural women drawn from two linked studies: the NFHS-2, conducted during 1998-1999
      and a follow-up study for a subgroup of women carried out during 2002-2003. Three
      dimensions of autonomy were used: financial autonomy, freedom of movement, and
      household decision-making. Marital violence was measured as experience of
      physical violence in the year prior to the follow-up survey. Findings indicate
      the protective effects of financial autonomy and freedom of movement in reducing
      the risk of marital violence in the overall model. Furthermore, region-wise
      analysis revealed that in the more gender equitable settings of south India,
      financial autonomy exerted a protective influence on risk of marital violence.
      However, in the more gender-stratified settings of north India, none of the
      dimensions of autonomy were found to have any protective effect on women's risk
      of marital violence. Results argue for an increased focus on strategies aimed at
      improving women's financial status through livelihood skill-building
      opportunities, development of a strong savings orientation, and asset-building
      options. 

PMID- 24097912
TI  - Prothrombin complex concentrate safely reverses warfarin-related bleeding.

PMID- 24097913
TI  - Combination of inhaled corticosteroid and bronchodilator-induced delirium in an
      elderly patient with lung disease.
AB  - Steroid psychosis has been well described with oral glucocorticoids, however, our
      search of the literature did not identify an association between delirium and the
      combination of inhaled glucocorticoids and long-acting beta-agonists. We describe
      the occurrence of delirium with the combination of an inhaled glucocorticoid and
      bronchodilator. An elderly male described confusion and hallucinations within 1
      week after initiation of budesonide/formoterol for chronic obstructive pulmonary
      disease. The combination inhaler was discontinued with resolution of symptoms.
      Several weeks later, the patient was hospitalized and restarted on the
      combination inhaler. The patient was alert and oriented on admission, however,
      confusion and hallucinations progressed throughout his hospital stay. The
      combination inhaler was discontinued and his confusion and hallucinations
      resolved by discharge. The temporal relationship of these events and a probable
      Naranjo association allows for reasonable assumption that the use of the
      budesonide/formoterol combination inhaler caused or contributed to the
      occurrences of delirium in this elderly patient. The onset of delirium was likely
      due to the systemic absorption of the glucocorticoid from lung deposition,
      complicated in an individual with several predisposing risk factors for delirium.
      Health care providers should be aware of this potential adverse drug reaction
      when prescribing inhaled medications to older patients at risk for delirium. 

PMID- 24097914
TI  - MHRA recommendations on the use of intravenous acetylcysteine in paracetamol
      overdose.

PMID- 24097915
TI  - Looking beyond supply: a systematic literature review of demand-side barriers to
      health service utilization in the mountains of Nepal.
AB  - Significant disparities in reproductive, maternal, newborn, and child health
      (RMNCH) outcomes and intervention coverage exist between the Mountains and other
      ecoregions of Nepal. Delivery of essential health services to remote mountainous
      areas is challenging and access is a known barrier to utilization. However, the
      contribution of demand-side barriers is poorly understood. Consequently, policies
      and programs cannot strategically target constraints to increase coverage. This
      systematic review identifies demand-side barriers to utilization of RMNCH
      services in the Mountain districts of Nepal. Research was drawn from MEDLINE, Web
      of Science, Scopus, Google Scholar, Eldis, and unpublished literature. Beyond
      inaccessibility, utilization is undermined by costs of care-seeking, traditional
      attitudes and practices, low status of women, limited health knowledge,
      dissatisfaction with service quality, and low and inequitable care by community
      health workers. The intensity and repercussions of these barriers are of greater
      magnitude in the Mountains where delayed care-seeking combines with long
      distances for critical health consequences. 

PMID- 24097916
TI  - Determinants of metabolic syndrome in Chinese schoolchildren.
AB  - The objective of this study was to identify the potential risk factors of
      metabolic syndrome (MetS) among Chinese schoolchildren. A cross-sectional study
      among 624 children (357 boys and 267 girls, aged 9.6 +/- 0.7 years) was conducted
      in Wuhan, China, from May to June 2010. MetS was defined according to the
      criteria proposed by De Ferranti and the International Diabetes Federation (IDF)
      criteria. Data on cardiorespiratory fitness (CRF), household income, parental
      hypertension, and children's personal information, including birth weight,
      preterm birth, and breast-feeding, reported by their parents were obtained.
      Multiple logistic regression showed that CRF (odds ratio [OR] = 0.68; 95%
      confidence interval [CI] = 0.60-0.77), breast-feeding (OR = 0.32; 95% CI = 0.10
      0.97), and paternal hypertension (OR = 5.06; 95% CI = 1.20-21.37) were all
      independently associated with MetS. In conclusion, low CRF and paternal
      hypertension significantly increase the risk, whereas breast-feeding may reduce
      the risk of MetS among Chinese schoolchildren. 

PMID- 24097917
TI  - Intention to engage in preventive behaviors in response to the A/H1N1 pandemic
      among university entrants in four Chinese cities.
AB  - This study examined the factors influencing the uptake of A/H1N1-related
      preventive behaviors among Chinese university students. During the 2009 A/H1N1
      pandemic, a survey was administered to 2882 university students across 4 Chinese
      cities. We found greater self-efficacy and a stronger belief in the benefits of
      preventive behaviors to be associated with the intended adoption of preventive
      behaviors. However, knowledge about the transmission of A/H1N1 was not associated
      with the intent to engage in preventive behaviors. These results may be used to
      inform pandemic prevention campaigns for university students in the region. 

PMID- 24097918
TI  - Gaps in health-related quality of life among survivors of cancer and
      cardiovascular disease: the Korean National Health and Nutrition Examination
      Survey, 2005 (KNHANES III).
AB  - Few studies performed so far have weighed the health-related quality of life
      (HRQoL) of cancer survivors against that of cardiovascular disease (CVD)
      survivors. This study was based on data obtained from the Third Korean National
      Health and Nutrition Examination Survey. Of adults with available EuroQoL (EQ)
      information, a total 23 370 individuals (658 CVD survivors, 389 cancer survivors,
      and 22 323 controls) remained in the final analysis. Cancer survivors have the
      lowest HRQoL scales among the 3 groups, independent of age. The HRQoL of young
      cancer survivors was as impaired as that of older cancer survivors, whereas the
      HRQoL of CVD survivors and controls decreased with increasing age. Cancer
      survivors also have more problems in all domains of EQ-5D, especially domains of
      pain/discomfort and anxiety/depression. The study suggests that cancer survivors
      should receive more intensive attention to develop means of identifying them and
      to improve their quality of life. 

PMID- 24097919
TI  - Effect of low income on health-related quality of life: a cross-sectional study
      in northeast China.
AB  - Following the dramatic socioeconomic transition since the 1980s in China, some
      people became unemployed and experienced a significant drop in income. The aim of
      this study was to assess the effects of low income on health-related quality of
      life (HRQOL) among the population in northeast China. A total of 5100 individuals
      in northeast China were randomly sampled and investigated using the 36-item Short
      Form Health Survey (SF-36) from November 2005 to October 2006. According to the
      monthly per capita income level, the population was divided into different groups
      for analysis. Multiple linear regressions showed that low income, older age,
      disease, and unemployment were the important factors that could lead to worse
      HRQOL. Covariance analysis showed that there were significant differences in
      HRQOL scores among the subgroups of the low-income population. When the income
      level increased, HRQOL scores improved. This study could provide valuable
      information for planning integrated economic and public health policies to
      improve the health of people living in poverty. 

PMID- 24097920
TI  - Effect of the September 2009 Sumatra earthquake on reproductive health services
      and MDG 5 in the city of Padang, Indonesia.
AB  - Indonesia has been making good progress in reproductive health (RH) outcome. This
      study aimed to examine the effect of the September 2009 Sumatra earthquake on
      availability and accessibility of RH services and its possible impact on local
      Millennium Development Goals (MDGs). Twenty-six health facilities in Padang City
      were reviewed and 667 clients directly interviewed. Water supply shortage was
      most widespread and slowest to recover, taking more than 1 year to normalize.
      Antenatal and emergency obstetric care was minimally disrupted, and family
      planning practice of the study couples was not changed by the earthquake. The
      previous rate of improvement in maternal and child mortality was slowed down,
      whereas stillbirths increased after the earthquake. Thus, there is a need to
      speed up the recovery to achieve the local MDGs. 

PMID- 24097921
TI  - Trends in electric bike-related injury in China, 2004-2010.
AB  - This study describes electric bike-related injuries from 2004 to 2010, and
      suggests injury prevention strategies to reduce electric bike-related injuries in
      China and other countries. Electric bike-related injuries data were obtained from
      the Bureau of Traffic Management at the Ministry of Public Security. Linear
      regression was used to identify statistically significant trends in electric bike
      related injuries over the period. The results showed electric bike-related
      nonfatal injury rate had increased almost 4-fold and mortality rate increased 6
      fold from 2004 to 2010. Linear regression showed a significant increase of 0.23
      per 100 000 population per year (95% confidence interval = 0.18-0.29, P < .001)
      in the casualty rate from electric bike-related road traffic injuries. China will
      face new challenges arising from electric bike-related injuries. Programs need to
      be developed to prevent nonfatal injuries and fatalities caused by electric bike
      related crashes in this country. 

PMID- 24097922
TI  - Predictors of poor response after primary immunization of hepatitis B vaccines
      for infants and antibody seroprotection of booster in a metropolis of China.
AB  - To evaluate proportion and predictors of poor response in infants and appraise
      booster seroprotection, we surveyed 2047 infants in Shanghai and detected
      antibody to hepatitis B (HB) surface antigen (anti-HBs). Poor responders were
      randomized into 2 groups, given booster with 5 ug and 10 ug hepatitis B vaccine
      (HepB), respectively. Proportion of infants with titer <10 mIU/mL and 10 to 99
      mIU/mL was 1.86% and 15.14%, respectively. Multivariate logistic regression
      suggested infants of male, aged 13 to 18 months, premature, administered with 5
      ug HepB or mother positive for HB surface antigen (HBsAg) and HBe antigen (HBeAg)
      would more likely develop worse response. Difference of geometric mean
      concentration between the first and full booster was not statistically
      significant both for 5 ug and for 10 ug HepB groups. The seroprotective rate were
      higher for infants with 10 ug HepB than those with 5 ug HepB (P > .05).
      Therefore, it is concluded that booster for poor vaccinees with 10 ug HepB could
      achieve satisfactory seroprotection. 

PMID- 24097923
TI  - Work-related musculoskeletal pain among dentists in Madhya Pradesh, India:
      prevalence, associated risk factors, and preventive measures.
AB  - Dentists are at risk for developing musculoskeletal problems. This provided the
      impetus for a study of prevalence, distribution, and the associated risk factors
      of these problems in the dentist population of Madhya Pradesh, India. The data
      were analyzed from 213 dentists of Madhya Pradesh, India, who fulfilled the
      inclusion criteria and gave their consent for this cross-sectional study.
      Subjects were assessed by a special questionnaire using demographic details with
      working conditions. Chi-square test was used for the statistical analysis of the
      data. Of total 213 participants, 83.10% had at least one musculoskeletal pain in
      the past 12 months. Low back pain was most frequent (57.75%) followed by neck
      pain (31.17%) and wrist pain (17.84%). The pain was significantly prevalent among
      the group who worked in direct vision, without assistant, in standing position or
      following none of the fitness regimen. 

PMID- 24097924
TI  - Validation of an oral health-related quality of life measure for Cambodian
      children.
AB  - This study aimed to determine the impact of dental caries in terms of Oral Health
      Related Quality of Life (OHRQoL) for Cambodian children. The Child Perceptions
      Questionnaires (CPQ) were cross-culturally adapted and validated for the
      Cambodian population using a sample of 430 Cambodian children. The participants
      had a high caries burden, with a mean number of decayed-missing-and-filled
      deciduous tooth surfaces (dmfs) of 8.8 (SD = 11.1) and a mean DMFS of 3.7 (SD =
      5.5) for the permanent dentition. Two in 5 children had at least one pulpally
      involved tooth. There was a significant difference in mean CPQ8-10 and CPQ11-14
      scores by caries experience and by global item response for the respective age
      groups, with those in the more severe caries categories scoring higher. Similar
      gradients were apparent with the CPQ11-14 in the 8- to 10-year age-group. The
      differences in OHRQoL scores by caries experience demonstrate the construct
      validity of the CPQ11-14 for the 8- to 14-year age-group. 

PMID- 24097925
TI  - Factors associated with the timing of antenatal care seeking in Bangladesh.
AB  - This study investigates the factors affecting the timing of antenatal care (ANC)
      seeking among Bangladeshi women using the 2007 Bangladesh Demographic and Health
      Survey data. Overall, 52% of the most recently pregnant women sought skilled ANC.
      The most pronounced reason for not receiving the services was that it was "not
      needed." Of the women who sought ANC, 57% entered for ANC at the fourth month or
      later. The multivariate regression analysis revealed that maternal age, women's
      education, residence, wealth index, pregnancy intention status, child's birth
      order, and wanting more children were the important determinants of ANC services
      utilization. Wanting more children and contraception use were no longer
      independent contributors to late ANC entry. These barriers should also be
      addressed as part of health interventions through information education and
      communication programs to early entry to ANC. The need to reduce financial
      barriers to care is a major implication of this study. 

PMID- 24097926
TI  - Social capital and depression: does household context matter?
AB  - The purpose of this study is 2-fold: (1) to examine how much variance of
      depression is attributed to the household level and (2) to examine the
      relationships between individual- and household-level social capital and
      depression using multilevel analysis from the Korean Welfare Panel Study data.
      Results show that more than 30% of variance in depression is derived from
      household-level differences. Results also show that individual level of trust and
      satisfaction with relationships in the family and household level of satisfaction
      with relationships among family members was related to depression. The results
      imply that forming and increasing household or family-level social capital along
      with individual-level social capital may contribute to preventing depression. 

PMID- 24097927
TI  - Comparison between peer-led and teacher-led education in tuberculosis prevention
      in rural middle schools in Chongqing, China.
AB  - The aim of this study was to investigate the efficacy of tuberculosis (TB)
      education through a comparison of peer-led and teacher-led methods of education
      about TB prevention among middle school students in rural Chongqing, China. A
      preintervention and postintervention questionnaire survey was conducted in 2
      different middle school student groups to measure changes in knowledge, attitude,
      and practice (KAP) status of those students before and after each TB education
      program. Of 1265 students participating in the preintervention survey, 1176
      completed the postintervention survey. KAP scores of both peer-led and teacher
      led groups after intervention improved by as much as 2 times compared with before
      the intervention and those of the control group (P < .01). KAP scores of
      immediate evaluation were higher than those of long-term evaluation in the
      teacher-led education group (P < .01). The teacher-led group had a larger
      improvement than the peer-led group in practice scores (P < .01) in immediate
      effect evaluation. 

PMID- 24097928
TI  - Risk factors for leptospirosis infection in humans and implications for public
      health intervention in Indonesia and the Asia-Pacific region.
AB  - Prevention and control of leptospirosis require an understanding of risk factors.
      This review identifies risk factors associated with leptospirosis infection from
      countries in the Asia-Pacific region, and compares and contrasts these data with
      those available from Indonesia. MEDLINE, PubMed, and Scopus databases were used
      to search for relevant articles. Indonesian gray literature was searched for
      leptospirosis risk factor studies in Indonesia. A total of 34 articles were
      included in this review. The contrast between peer-reviewed publications and
      Indonesian gray literature revealed that the variety of risk factors associated
      with leptospirosis infection is region or area specific. The presence of skin
      wounds, the existence of rodents, especially rats, and activities related to
      contact with contaminated surface water are factors frequently reported to have
      significant association with leptospirosis infection in human in Indonesia and in
      other Asia-Pacific countries. 

PMID- 24097929
TI  - Stakeholder perceptions of a pharmacy-initiated tuberculosis referral program in
      Cambodia, 2005-2012.
AB  - Intensifying detection of tuberculosis (TB) symptomatic patients is a priority
      for Cambodia's National Tuberculosis Program, in a country where two-thirds of
      the population has latent TB infection. In 2005, the National Tuberculosis
      Program initiated a public-private mix (PPM) collaborative program with external
      and local stakeholders to identify and refer persons with TB symptoms from
      private sector pharmacies to public sector clinics for diagnosis and treatment.
      This qualitative study conducted in-depth interviews with organizational
      stakeholders to assess their perceptions of PPM program collaboration and its
      sustainability in the long term. Results showed that stakeholders perceived that
      collaboration and efficient management had contributed to positive program
      performance. However, stakeholders expressed anxiety over program sustainability
      should external resources be reduced. Recent developments in pharmacy
      undergraduate education and recognition of pharmacy providers' contribution to
      public health interventions may challenge PPM stakeholders to shift the paradigm
      from dependence on external agencies to confidence in local expertise and
      infrastructure. 

PMID- 24097930
TI  - Trauma-related symptoms in Sri Lankan adult survivors after the tsunami:
      pretraumatic and peritraumatic factors.
AB  - Limited research has addressed factors associated with psychological distress
      following disasters among non-Western populations. The 2004 tsunami affected 1.7
      million people across South Asia and Africa, with considerable variations in
      trauma-related outcomes. Pretraumatic and peritraumatic conditions associated
      with trauma-related symptoms in 305 Sri Lankan adult survivors (28% male, aged 18
      83 years; mean = 39.9 years; standard deviation = 15.3), clinically assessed 1
      month posttsunami, were evaluated retrospectively. Outcome measures were total
      scores on 11 trauma-related symptoms. Multivariate linear regression analyses
      tested for associations between pretraumatic and peritraumatic conditions and
      symptom scores, with peritraumatic conditions adjusted for pretraumatic
      variables. Pretraumatic conditions of female gender, employment, prior health and
      social issues, and substance use and peritraumatic conditions of loss of family,
      witnessing the tsunami, or suffering an injury were associated with trauma
      related symptoms. The findings facilitate understanding cultural contexts that
      define risk factors associated with trauma-related symptoms in Sri Lankans, which
      are critical for developing culturally appropriate interventions. 

PMID- 24097931
TI  - Adverse consequences of unintended pregnancy for maternal and child health in
      Nepal.
AB  - In Nepal, 26%-38% of recent births are estimated to be from unintended
      pregnancies, but little is known whether these pregnancies have adverse
      consequences for the health of the mother and child. Data from the 2011 Nepal
      Demographic and Health Survey are used to examine the hypothesis that unintended
      pregnancies are associated with negative health outcomes for both mothers and
      children. When the pregnancy was unintended (compared with when it was intended)
      mothers were more likely to receive inadequate prenatal care (odds ratio OR =
      1.50; 95% confidence interval [CI] = 1.28-1.77). They were also more likely to
      opt for home births (OR = 1.30; 95% CI = 1.11-1.52). Likewise, the resultant
      newborns of unintended pregnancies were more likely to receive inadequate
      immunization (OR = 1.18; 95% CI = 1.00-1.40) and to remain stunted (OR = 1.25;
      95% CI = 1.00-1.56). Findings suggest significant associations between unintended
      pregnancy and negative health outcomes for both mothers and children in Nepal. 

PMID- 24097932
TI  - Physical activity research in Hong Kong from 1987 to 2012: evidence on children
      and adolescents.
AB  - A comprehensive understanding of research on the physical activity (PA) of Hong
      Kong youth is necessary to develop specific and effective intervention
      strategies. This review summarizes existing evidence in studies on PA among the
      Hong Kong youth. An electronic literature search was conducted using MEDLINE,
      SPORTDiscus, ERIC, and HighWire database. Forty-five studies published from 1987
      to 2012 were included in this review. The findings are presented in five
      categories, namely, health benefits of PA, participation in PA, assessment of PA,
      correlates of PA, and interventions to promote PA. The results indicate that PA
      among the youth in Hong Kong has attracted concern in the past decade.
      Specifically, extensive studies focused on the areas of health benefits of PA,
      participation in PA, and correlates of PA. Research into context-specific
      correlates of PA and tailored PA promotion programs for the Hong Kong youth is
      warranted in the future.

PMID- 24097933
TI  - Prevalence of and associations with excessive daytime sleepiness in an Australian
      older population.
AB  - The aim of this research is to estimate the prevalence of excessive daytime
      sleepiness in an older population and associations with sociodemographic, health,
      and lifestyle factors using a cross-sectional, population-based study.
      Participants were men (1560) and women (1759), aged 55 to 85 years, enrolled in
      the Hunter Community Study, a longitudinal study of aging. Measurements were self
      reported questionnaires, biochemical measures, and clinical measures. Of the 3319
      participants, 3053 participants completed the Epworth Sleepiness Scale
      questionnaire. The prevalence of excessive daytime sleepiness was 15.3% overall
      and this was higher in males. In adjusted multivariate analysis, gender, working
      full time, body mass index, high-density and low-density lipoprotein cholesterol,
      Center for Epidemiologic Studies-Depression scale score, and Kessler
      psychological distress score were associated with excessive daytime sleepiness.
      Given the high prevalence of excessive daytime sleepiness observed in this study,
      further investigation and/or interventions to reduce adverse health outcomes,
      especially in males is warranted. 

PMID- 24097934
TI  - Predictors of health-promoting behavior associated with cardiovascular diseases
      among Korean blue-collar workers.
AB  - The aim of this study was to investigate the contribution of actual
      cardiovascular disease (CVD) risks, psychosocial and work-related factors as
      predictors of health behavior. A sample of 234 Korean blue-collar workers, who
      worked in small companies, was included in this cross-sectional study. Data
      collection included a survey; anthropometric and blood pressure measures; and
      blood sampling. Multiple regression analyses showed that the model explained 30%
      of the variance in health behavior of blue-collar workers. The significant
      predictors for health behavior included education level, perceived general
      health, greater family function, higher social support, decision latitude, and
      non-shift work. Future research should focus on incorporating these significant
      predictors into effective behavioral interventions designed to promote
      cardiovascular health in this population. 

PMID- 24097935
TI  - Factors causing delay of access to tuberculosis diagnosis among new, active
      tuberculosis patients: a prospective cohort study.
AB  - Few studies have examined, in a prospective cohort study, factors causing delay
      of access to tuberculosis (TB) diagnosis among new, active TB patients. A
      prospective cohort study (2009-2011) was carried out among 408 889 Chinese. Data
      on known/potential influencing factors were obtained from baseline
      questionnaires. We used stepwise logistic regression models to analyze the
      association between several known/potential influencing factors and diagnosis
      delay, assessed the current situation, and explored determinants of diagnosis
      delay. During follow-up and final visits, 202 new, active TB patients were found.
      Median patient delay was 5.4 (quartile 2.7-26) weeks, health system delay was 0
      (quartile 0-1.6) weeks, and diagnosis delay was 9.9 (quartile 3.1-28.1) weeks.
      The influencing factors on patient delay were age and duration of symptoms.
      Smoking and sputum smear status were influencing factors for health system delay,
      and duration of symptoms was one of the factors for diagnosis delay. These
      findings provide information on the current situation of diagnosis delay and
      evidence for specific strategy development for TB control in China. 

PMID- 24097936
TI  - Health systems and noncommunicable diseases in the Asia-Pacific region: a review
      of the published literature.
AB  - Addressing the growing burden of noncommunicable diseases (NCDs) in countries of
      the Asia-Pacific region requires well-functioning health systems. In low- and
      middle-income countries (LMICs), however, health systems are generally
      characterized by inadequate financial and human resources, unsuitable service
      delivery models, and weak information systems. The aims of this review were to
      identify (a) health systems interventions being implemented to deliver NCD
      programs and services and their outcomes and (b) the health systems bottlenecks
      impeding access to or delivery of these programs and services in LMICs of the
      Asia-Pacific region. A search of 4 databases for literature published between
      1990 and 2010 retrieved 36 relevant studies. For each study, information on basic
      characteristics, type of health systems bottleneck/intervention, and outcome was
      extracted, and methodological quality appraised. Health systems interventions and
      bottlenecks were classified as per the World Health Organization health systems
      building blocks framework. The review identified interventions and bottlenecks in
      the building blocks of service delivery, health workforce, financing, health
      information systems, and medical products, vaccines, and technologies. Studies,
      however, were heterogeneous in methodologies used, and the overall quality was
      generally low. There are several gaps in the evidence base around NCDs in the
      Asia-Pacific region that require further investigation. 

PMID- 24097938
TI  - Child marriage and its association with adverse reproductive outcomes for women
      in Bangladesh.
AB  - This study examines the prevalence of child marriage and its effect on
      reproductive outcomes among women in Bangladesh using the most recent 2011
      Bangladesh Demographic and Health Survey data. Both bivariate and multivariate
      statistical techniques used in the study yielded quantitatively important and
      reliable estimates of child marriage and its impact on adverse reproductive and
      health outcomes. Overall, 77% of the marriages among women aged 20 to 49 years
      old took place before the age of 18 years. Women's education is the most single
      significant determinant of child marriage. Findings revealed that after being
      adjusted for sociodemographic factors, child marriage significantly (P < .001)
      increases the likelihood of stillbirth/miscarriage (odds ratio [OR] = 1.80; 95%
      confidence interval [CI] = 1.45-2.24) and pregnancy termination (OR = 1.24; 95%
      CI = 1.12-1.38). Programs should aim to retain girls in school for longer periods
      not only to raise the age at first marriage but also for sound reproductive
      health and overall social development of Bangladesh. 

PMID- 24097937
TI  - Effectiveness of acupuncture for smoking cessation in a Chinese population.
AB  - An observational study was conducted to evaluate the effectiveness of acupuncture
      for smoking cessation, and determine predictors for successful quitters. Smokers
      received at least 6 sessions of body acupuncture provided by Chinese medicine
      practitioners and initiated self-administered auricular acupuncture. We
      determined self-report 26-week and 52-week quit rates by intention-to-treat
      analysis and examined predictors for successful quitting by univariate and
      multivariate analyses. A total of 1002 smokers were recruited; 26-week and 52
      week quit rates were 16.8% and 15.8%, respectively. Male sex, older age, lower
      nicotine dependence level, and number of body acupuncture and counseling sessions
      received were associated with successful quitting. A multiple logistic regression
      model showed that sex, nicotine dependence level, and number of body acupuncture
      sessions received were predictors for successful quitting. Body and auricular
      acupuncture is effective in smoking cessation and should be considered as an
      alternative to help smokers in quitting, especially for those whose past attempts
      using conventional methods were in vain. 

PMID- 24097939
TI  - Strengthening primary health care in low- and middle-income countries: generating
      evidence through evaluation.
AB  - Since the publication of the World Health Report 2008, there has been renewed
      interest in the potential of primary health care (PHC) to deliver global health
      policy agendas. The WHO Western Pacific Regional Strategy 2010 states that health
      systems in low- and middle-income countries (LMICs) can be strengthened using PHC
      values as core principles. This review article explores the development of an
      evidence-based approach for assessing the effectiveness of PHC programs and
      interventions in LMICs. A realist review method was used to investigate whether
      there is any internationally consistent approach to evaluating PHC. Studies from
      LMICs using an explicit methodology or framework for measuring PHC effectiveness
      were collated. Databases of published articles were searched, and a review of
      gray literature was undertaken to identify relevant reports. The review found no
      consistent approach for assessing the effectiveness of PHC interventions in
      LMICs. An innovative approach used in China, which developed a set of core
      community health facility indicators based on stakeholder input, does show some
      potential for use in other LMIC contexts. 

PMID- 24097941
TI  - D-amino acids indirectly inhibit biofilm formation in Bacillus subtilis by
      interfering with protein synthesis.
AB  - The soil bacterium Bacillus subtilis forms biofilms on surfaces and at air-liquid
      interfaces. It was previously reported that these biofilms disassemble late in
      their life cycle and that conditioned medium from late-stage biofilms inhibits
      biofilm formation. Such medium contained a mixture of D-leucine, D-methionine, D
      tryptophan, and D-tyrosine and was reported to inhibit biofilm formation via the
      incorporation of these D-amino acids into the cell wall. Here, we show that L
      amino acids were able to specifically reverse the inhibitory effects of their
      cognate D-amino acids. We also show that D-amino acids inhibited growth and the
      expression of biofilm matrix genes at concentrations that inhibit biofilm
      formation. Finally, we report that the strain routinely used to study biofilm
      formation has a mutation in the gene (dtd) encoding D-tyrosyl-tRNA deacylase, an
      enzyme that prevents the misincorporation of D-amino acids into protein in B.
      subtilis. When we repaired the dtd gene, B. subtilis became resistant to the
      biofilm-inhibitory effects of D-amino acids without losing the ability to
      incorporate at least one noncanonical D-amino acid, D-tryptophan, into the
      peptidoglycan peptide side chain. We conclude that the susceptibility of B.
      subtilis to the biofilm-inhibitory effects of D-amino acids is largely, if not
      entirely, due to their toxic effects on protein synthesis.

PMID- 24097942
TI  - The syp enhancer sequence plays a key role in transcriptional activation by the
      sigma54-dependent response regulator SypG and in biofilm formation and host
      colonization by Vibrio fischeri.
AB  - Biofilm formation by Vibrio fischeri is a complex process that requires multiple
      regulators. One such regulator, the NtrC-like response regulator SypG, controls
      biofilm formation and host colonization by V. fischeri via its impact on
      transcription of the symbiosis polysaccharide (syp) locus. SypG is predicted to
      activate syp transcription by binding to the syp enhancer (SE), a conserved
      sequence located upstream of four syp promoters. In this study, we performed an
      in-depth analysis of the sequences necessary for SypG to promote syp
      transcription and biofilm formation. We found that the SE sequence is necessary
      for SypG-mediated syp transcription, identified individual bases necessary for
      efficient activation, and determined that SypG is able to bind to syp promoter
      regions. We also identified SE sequences outside the syp locus and established
      that SypG recognizes these sequences as well. Finally, deletion of the SE
      sequence upstream of sypA led to defects in both biofilm formation and host
      colonization that could be restored by reintroducing the SE sequence into its
      native location in the chromosome. This work thus fills in critical gaps in
      knowledge of the Syp regulatory circuit by demonstrating a role for the SE
      sequence in SypG-dependent control of biofilm formation and host colonization and
      by identifying new putative regulon members. It may also provide useful insights
      into other bacteria, such as Vibrio vulnificus and Vibrio parahaemolyticus, that
      have syp-like loci and conserved SE sequences. 

PMID- 24097943
TI  - Alkyl hydroperoxide reductase repair by Helicobacter pylori methionine sulfoxide
      reductase.
AB  - Protein exposure to oxidants such as HOCl leads to formation of methionine
      sulfoxide (MetSO) residues, which can be repaired by methionine sulfoxide
      reductase (Msr). A Helicobacter pylori msr strain was more sensitive to HOCl
      mediated killing than the parent. Because of its abundance in H. pylori and its
      high methionine content, alkyl hydroperoxide reductase C (AhpC) was hypothesized
      to be prone to methionine oxidation. AhpC was expressed as a recombinant protein
      in Escherichia coli. AhpC activity was abolished by HOCl, while all six
      methionine residues of the enzyme were fully to partially oxidized. Upon
      incubation with a Msr repair mixture, AhpC activity was restored to nonoxidized
      levels and the MetSO residues were repaired to methionine, albeit to different
      degrees. The two most highly oxidized and then Msr-repaired methionine residues
      in AhpC, Met101 and Met133, were replaced with isoleucine residues by site
      directed mutagenesis, either individually or together. E. coli cells expressing
      variant versions were more sensitive to t-butyl hydroperoxide than cells
      expressing native protein, and purified AhpC variant proteins had 5% to 39% of
      the native enzyme activity. Variant proteins were still able to oligomerize like
      the native version, and circular dichroism (CD) spectra of variant proteins
      revealed no significant change in AhpC conformation, indicating that the loss of
      activity in these variants was not related to major structural alterations. Our
      results suggest that both Met101 and Met133 residues are important for AhpC
      catalytic activity and that their integrity relies on the presence of a
      functional Msr. 

PMID- 24097944
TI  - Structural and functional studies of gpX of Escherichia coli phage P2 reveal a
      widespread role for LysM domains in the baseplates of contractile-tailed phages.
AB  - A variety of bacterial pathogenicity determinants, including the type VI
      secretion system and the virulence cassettes from Photorhabdus and Serratia,
      share an evolutionary origin with contractile-tailed myophages. The well
      characterized Escherichia coli phage P2 provides an excellent system for studies
      related to these systems, as its protein composition appears to represent the
      "minimal" myophage tail. In this study, we used nuclear magnetic resonance (NMR)
      spectroscopy to determine the solution structure of gpX, a 68-residue tail
      baseplate protein. Although the sequence and structure of gpX are similar to
      those of LysM domains, which are a large family associated with peptidoglycan
      binding, we did not detect a peptidoglycan-binding activity for gpX. However,
      bioinformatic analysis revealed that half of all myophages, including all that
      possess phage T4-like baseplates, encode a tail protein with a LysM-like domain,
      emphasizing a widespread role for this domain in baseplate function. While phage
      P2 gpX comprises only a single LysM domain, many myophages display LysM domain
      fusions with other tail proteins, such as the DNA circulation protein found in Mu
      like phages and gp53 of T4-like phages. Electron microscopy of P2 phage particles
      with an incorporated gpX-maltose binding protein fusion revealed that gpX is
      located at the top of the baseplate, near the junction of the baseplate and tail
      tube. gpW, the orthologue of phage T4 gp25, was also found to localize to this
      region. A general colocalization of LysM-like domains and gpW homologues in
      diverse phages is supported by our bioinformatic analysis. 

PMID- 24097946
TI  - Description of a riboflavin biosynthetic gene variant prevalent in the phylum
      Proteobacteria.
AB  - Riboflavin (vitamin B2) is the precursor of flavin mononucleotide and flavin
      adenine dinucleotide, which are cofactors essential for a host of intracellular
      redox reactions. Microorganisms synthesize flavins de novo to fulfill nutritional
      requirements, but it is becoming increasingly clear that flavins play a wider
      role in cellular physiology than was previously appreciated. Flavins mediate
      diverse processes beyond the cytoplasmic membrane, including iron acquisition,
      extracellular respiration, and interspecies interactions. While investigating the
      regulation of flavin electron shuttle biosynthesis in the Gram-negative
      gammaproteobacterium Shewanella oneidensis, we discovered that a riboflavin
      biosynthetic gene (ribBA) annotated as encoding a bifunctional 3,4-dihydroxy-2
      butanone 4-phosphate (DHBP) synthase/GTP cyclohydrolase II does not possess both
      functions. The novel gene, renamed ribBX here, encodes an amino-terminal DHBP
      synthase domain. The carboxy-terminal end of RibBX not only lacks GTP
      cyclohydrolase II activity but also has evolved a different function altogether
      in S. oneidensis, regulating the activity of the DHBP synthase domain.
      Phylogenetic analysis revealed that the misannotation of ribBX as ribBA is
      rampant throughout the phylum Proteobacteria (40% of 2,173 annotated ribBA genes)
      and that ribBX emerged early in the evolution of this group of microorganisms. We
      examined the functionality of representative ribBX genes from Beta-, Gamma-, and
      Epsilonproteobacteria and found that, consistent with sequence-based predictions,
      the encoded GTP cyclohydrolase II domains lack catalytic activity. The
      persistence of ribBX in the genomes of so many phylogenetically divergent
      bacterial species lends weight to the argument that ribBX has evolved a function
      which lends a selective advantage to the host. 

PMID- 24097945
TI  - Pseudomonas aeruginosa AlgR phosphorylation modulates rhamnolipid production and
      motility.
AB  - AlgR is a key Pseudomonas aeruginosa transcriptional response regulator required
      for virulence. AlgR activates alginate production and twitching motility but
      represses the Rhl quorum-sensing (QS) system, including rhamnolipid production.
      The role of AlgR phosphorylation is enigmatic, since phosphorylated AlgR (AlgR-P)
      is required for twitching motility through the fimU promoter but is not required
      for the activation of alginate production. In order to examine the role of AlgR
      phosphorylation in vivo, a PAO1 algRD54E strain (with algR encoding a D-to-E
      change at position 54), which constitutively activates fimU transcription and
      exhibits twitching motility, was created. A corresponding PAO1 algRD54N strain
      (with algR encoding a D-to-N change at position 54) that does not activate fimU
      or twitching motility was compared to PAO1, PAO1 algRD54E, PAO1 DeltaalgZ
      (deletion of the algZ [fimS] gene, encoding a putative histidine kinase), and
      PAO1 DeltaalgR for swarming motility, rhamnolipid production, and rhlA
      transcription. PAO1 and PAO1 algRD54E produced approximately 2-fold-higher levels
      of rhamnolipids than PAO1 algRD54N and PAO1 DeltaalgZ, thereby indicating that
      phosphorylated AlgR is required for normal rhamnolipid production. Examination of
      purified AlgR, AlgR-P, AlgR D54N, and AlgR D54E showed that AlgR-P and AlgR D54E
      bound preferentially to the fimU and rhlA promoters. Additionally, AlgR-P bound
      specifically to two sites within the rhlA promoter that were not bound by
      unphosphorylated AlgR. Taken together, these results indicate that phosphorylated
      AlgR-P has increased affinity for the rhlA promoter and is required for the
      coordinate activation of twitching motility, rhamnolipid production, and swarming
      motility in P. aeruginosa. 

PMID- 24097947
TI  - The conserved DNA-binding protein WhiA is involved in cell division in Bacillus
      subtilis.
AB  - Bacterial cell division is a highly coordinated process that begins with the
      polymerization of the tubulin-like protein FtsZ at midcell. FtsZ polymerization
      is regulated by a set of conserved cell division proteins, including ZapA.
      However, a zapA mutation does not result in a clear phenotype in Bacillus
      subtilis. In this study, we used a synthetic-lethal screen to find genes that
      become essential when ZapA is mutated. Three transposon insertions were found in
      yvcL. The deletion of yvcL in a wild-type background had only a mild effect on
      growth, but a yvcL zapA double mutant is very filamentous and sick. This
      filamentation is caused by a strong reduction in FtsZ-ring assembly, suggesting
      that YvcL is involved in an early stage of cell division. YvcL is 25% identical
      and 50% similar to the Streptomyces coelicolor transcription factor WhiA, which
      induces ftsZ and is required for septation of aerial hyphae during sporulation.
      Using green fluorescent protein fusions, we show that YvcL localizes at the
      nucleoid. Surprisingly, transcriptome analyses in combination with a ChIP-on-chip
      assay gave no indication that YvcL functions as a transcription factor. To gain
      more insight into the function of YvcL, we searched for suppressors of the
      filamentous phenotype of a yvcL zapA double mutant. Transposon insertions in gtaB
      and pgcA restored normal cell division of the double mutant. The corresponding
      proteins have been implicated in the metabolic sensing of cell division. We
      conclude that YvcL (WhiA) is involved in cell division in B. subtilis through an
      as-yet-unknown mechanism. 

PMID- 24097948
TI  - Interactions of NBU1 IntN1 and Orf2x proteins with attachment site DNA.
AB  - NBU1 is a mobilizable transposon found in Bacteroides spp. Mobilizable
      transposons require gene products from coresident conjugative transposons for
      excision and transfer to recipient cells. The integration of NBU1 requires IntN1,
      which has been identified as a tyrosine recombinase, as well as Bacteroides host
      factor BHFa. Excision of NBU1 is a more complicated process, involving five
      element-encoded proteins (IntN1, Orf2, Orf2x, Orf3, and PrmN1) as well as a
      Bacteroides host factor and a cis-acting DNA sequence. Little has been known
      about what role the proteins play in excision, although IntN1 and Orf2x have been
      shown to be the only proteins absolutely required for detectable excision. To
      determine where IntN1 and Orf2x bind during the excision of NBU1, both proteins
      were partially purified and tested in DNase I footprinting experiments with the
      excisive attachment sites attL and attR. The results demonstrate that IntN1 binds
      to four core-type sites that flank the region of cleavage and strand exchange, as
      well as six arm-type sites. A unique feature of the system is the location of
      DR2a and DR2b arm-type sites immediately downstream of the attL core. The DR1a,
      DR1b, DR3a, and DR3b arm-type sites were shown to be required for in vitro
      integration of NBU1. In addition, we have identified one Orf2x binding site (O1)
      on attL as well as a dA+dT-rich upstream element that is required for Orf2x
      interactions with O1. 

PMID- 24097949
TI  - Conserved pyridoxal protein that regulates Ile and Val metabolism.
AB  - Escherichia coli YggS is a member of the highly conserved uncharacterized protein
      family that binds pyridoxal 5'-phosphate (PLP). To assist with the functional
      assignment of the YggS family, in vivo and in vitro analyses were performed using
      a yggS-deficient E. coli strain (DeltayggS) and a purified form of YggS,
      respectively. In the stationary phase, the DeltayggS strain exhibited a
      completely different intracellular pool of amino acids and produced a significant
      amount of l-Val in the culture medium. The log-phase DeltayggS strain accumulated
      2-ketobutyrate, its aminated compound 2-aminobutyrate, and, to a lesser extent, l
      Val. It also exhibited a 1.3- to 2.6-fold increase in the levels of Ile and Val
      metabolic enzymes. The fact that similar phenotypes were induced in wild-type E.
      coli by the exogenous addition of 2-ketobutyrate and 2-aminobutyrate indicates
      that the 2 compounds contribute to the DeltayggS phenotypes. We showed that the
      initial cause of the keto acid imbalance was the reduced availability of coenzyme
      A (CoA); supplementation with pantothenate, which is a CoA precursor, fully
      reversed phenotypes conferred by the yggS mutation. The plasmid-borne expression
      of YggS and orthologs from Bacillus subtilis, Saccharomyces cerevisiae, and
      humans fully rescued the DeltayggS phenotypes. Expression of a mutant YggS
      lacking PLP-binding ability, however, did not reverse the DeltayggS phenotypes.
      These results demonstrate for the first time that YggS controls Ile and Val
      metabolism by modulating 2-ketobutyrate and CoA availability. Its function
      depends on PLP, and it is highly conserved in a wide range species, from bacteria
      to humans. 

PMID- 24097950
TI  - Evolutionary analysis of Burkholderia pseudomallei identifies putative novel
      virulence genes, including a microbial regulator of host cell autophagy.
AB  - Burkholderia pseudomallei, the causative agent of melioidosis, contains a large
      pathogen genome (7.2 Mb) with ~2,000 genes of putative or unknown function.
      Interactions with potential hosts and environmental factors may induce rapid
      adaptations in these B. pseudomallei genes, which can be discerned through
      evolutionary analysis of multiple B. pseudomallei genomes. Here we show that
      several previously uncharacterized B. pseudomallei genes bearing genetic
      signatures of rapid adaptation (positive selection) can induce diverse cellular
      phenotypes when expressed in mammalian cells. Notably, several of these
      phenotypes are plausibly related to virulence, including multinuclear giant cell
      formation, apoptosis, and autophagy induction. Specifically, we show that
      BPSS0180, a type VI cluster-associated gene, is capable of inducing autophagy in
      both phagocytic and nonphagocytic mammalian cells. Following infection of
      macrophages, a B. pseudomallei mutant disrupted in BPSS0180 exhibited
      significantly decreased colocalization with LC3 and impaired intracellular
      survival; these phenotypes were rescued by introduction of an intact BPSS0180
      gene. The results suggest that BPSS0180 may be a novel inducer of host cell
      autophagy that contributes to B. pseudomallei intracellular growth. More
      generally, our study highlights the utility of applying evolutionary principles
      to microbial genomes to identify novel virulence genes. 

PMID- 24097951
TI  - Identification and characterization of novel Helicobacter pylori apo-fur
      regulated target genes.
AB  - In Helicobacter pylori, the ferric uptake regulator (Fur) has evolved additional
      regulatory functions not seen in other bacteria; it can repress and activate
      different groups of genes in both its iron-bound and apo forms. Because little is
      understood about the process of apo-Fur repression and because only two apo-Fur
      repressed genes (pfr and sodB) have previously been identified, we sought to
      expand our understanding of this type of regulation. Utilizing published genomic
      studies, we selected three potential new apo-Fur-regulated gene targets: serB,
      hydA, and the cytochrome c553 gene. Transcriptional analyses confirmed Fur
      dependent repression of these genes in the absence of iron, as well as
      derepression in the absence of Fur. Binding studies showed that apo-Fur directly
      interacted with the suspected hydA and cytochrome c553 promoters but not that of
      serB, which was subsequently shown to be cotranscribed with pfr; apo-Fur
      dependent regulation occurred at the pfr promoter. Alignments of apo-regulated
      promoter regions revealed a conserved, 6-bp consensus sequence (AAATGA). DNase I
      footprinting showed that this sequence lies within the protected regions of the
      pfr and hydA promoters. Moreover, mutation of the sequence in the pfr promoter
      abrogated Fur binding and DNase protection. Likewise, fluorescence anisotropy
      studies and binding studies with mutated consensus sequences showed that the
      sequence was important for apo-Fur binding to the pfr promoter. Together these
      studies expand the known apo-Fur regulon in H. pylori and characterize the first
      reported apo-Fur box sequence. 

PMID- 24097952
TI  - Biochemical activities of Streptococcus pneumoniae serotype 2 capsular
      glycosyltransferases and significance of suppressor mutations affecting the
      initiating glycosyltransferase Cps2E.
AB  - The capsular polysaccharide (CPS) is essential for Streptococcus pneumoniae
      virulence. Its synthesis requires multiple enzymes, and defects that block
      completion of the pathway can be lethal in the absence of secondary suppressor
      mutations. In this study, we examined the functions of three capsular
      glycosyltransferases (Cps2F, Cps2G, and Cps2I) involved in serotype 2 CPS
      synthesis, whose deletions select for secondary mutations. We demonstrate that
      Cps2F is a rhamnosyltransferase that catalyzes addition of the third and fourth
      sugars in the capsule repeat unit, while Cps2G adds the fifth sugar (glucose).
      Addition of the terminal residue (glucuronic acid) could not be detected;
      however, activities of the other glycosyltransferases together with bioinformatic
      analyses suggest that this step is mediated by Cps2I. Most of the secondary
      suppressor mutations resulting from loss of these enzymes occur in cps2E, the
      gene encoding the initiating glycosyltransferase. Examination of the 69 S.
      pneumoniae serotypes containing Cps2E homologues yielded a consensus amino acid
      sequence for this protein and demonstrated that there is a highly significant
      association between the residues that are 100% conserved and those altered by
      suppressor mutations. Cps2E contains an extracytoplasmic loop whose function is
      unknown. Among our collection of mutants, six contained missense mutations
      affecting amino acids in the extracytoplasmic loop. These residues are highly
      conserved among S. pneumoniae Cps2E homologues, and mutations therein severely
      reduced CPS synthesis and Cps2E activity. The critical functions of these amino
      acids suggest a role for the Cps2E extracytoplasmic loop in initiation, and
      possibly regulation, of capsule synthesis. 

PMID- 24097953
TI  - Characterization of the GbdR regulon in Pseudomonas aeruginosa.
AB  - Pseudomonas aeruginosa displays tremendous metabolic diversity, controlled in
      part by the abundance of transcription regulators in the genome. We have been
      investigating P. aeruginosa's response to the host, particularly changes
      regulated by the host-derived quaternary amines choline and glycine betaine (GB).
      We previously identified GbdR as an AraC family transcription factor that
      directly regulates choline acquisition from host phospholipids (via binding to
      plcH and pchP promoters), is required for catabolism of the choline metabolite
      GB, and is an activator that induces transcription in response to GB or
      dimethylglycine. Our goal was to characterize the GbdR regulon in P. aeruginosa
      by using genetics and chemical biology in combination with transcriptomics and in
      vitro DNA-binding assays. Here we show that GbdR activation regulates
      transcription of 26 genes from 12 promoters, 11 of which have measureable binding
      to GbdR in vitro. The GbdR regulon includes the genes encoding GB,
      dimethylglycine, sarcosine, glycine, and serine catabolic enzymes and the BetX
      and CbcXWV quaternary amine transport proteins. We characterized the GbdR
      consensus binding site and used it to identify that the recently characterized
      acetylcholine esterase gene, choE (PA4921), is also regulated by GbdR. The
      regulon member not directly controlled by GbdR is the secreted lipase gene lipA,
      which was also the only regulon member repressed under GbdR-activating
      conditions. Determination of the GbdR regulon provides deeper understanding of
      how GbdR links bacterial metabolism and virulence. Additionally, identification
      of two uncharacterized regulon members suggests roles for these proteins in
      response to choline metabolites. 

PMID- 24097955
TI  - In this issue of Occupational Medicine.

PMID- 24097954
TI  - Cellulose as an architectural element in spatially structured Escherichia coli
      biofilms.
AB  - Morphological form in multicellular aggregates emerges from the interplay of
      genetic constitution and environmental signals. Bacterial macrocolony biofilms,
      which form intricate three-dimensional structures, such as large and often
      radially oriented ridges, concentric rings, and elaborate wrinkles, provide a
      unique opportunity to understand this interplay of "nature and nurture" in
      morphogenesis at the molecular level. Macrocolony morphology depends on self
      produced extracellular matrix components. In Escherichia coli, these are
      stationary phase-induced amyloid curli fibers and cellulose. While the widely
      used "domesticated" E. coli K-12 laboratory strains are unable to generate
      cellulose, we could restore cellulose production and macrocolony morphology of E.
      coli K-12 strain W3110 by "repairing" a single chromosomal SNP in the bcs operon.
      Using scanning electron and fluorescence microscopy, cellulose filaments, sheets
      and nanocomposites with curli fibers were localized in situ at cellular
      resolution within the physiologically two-layered macrocolony biofilms of this
      "de-domesticated" strain. As an architectural element, cellulose confers cohesion
      and elasticity, i.e., tissue-like properties that-together with the cell-encasing
      curli fiber network and geometrical constraints in a growing colony-explain the
      formation of long and high ridges and elaborate wrinkles of wild-type
      macrocolonies. In contrast, a biofilm matrix consisting of the curli fiber
      network only is brittle and breaks into a pattern of concentric dome-shaped rings
      separated by deep crevices. These studies now set the stage for clarifying how
      regulatory networks and in particular c-di-GMP signaling operate in the three
      dimensional space of highly structured and "tissue-like" bacterial biofilms. 

PMID- 24097956
TI  - Occupational screening of health care workers for tuberculosis infection:
      tuberculin skin testing or interferon-gamma release assays?

PMID- 24097957
TI  - James Ensor, the bad doctors 1892.

PMID- 24097958
TI  - The rewards of rural training in the Scottish Highlands.

PMID- 24097959
TI  - Time to ditch Occupational Health.

PMID- 24097960
TI  - Radical reform follows normalised deviance.

PMID- 24097961
TI  - General practice in the United Kingdom: meeting the challenges of the early 21st
      century.

PMID- 24097962
TI  - Prevention of influenza at Hajj: applications for mass gatherings.

PMID- 24097963
TI  - Clinical sensemaking: a systematic approach to reduce the impact of normalised
      deviance in the medical profession.

PMID- 24097964
TI  - The origins of vaccination: no inoculation, no vaccination.

PMID- 24097965
TI  - The interaction of scientific evidence and politics in debates about preventing
      malaria in 1925.

PMID- 24097969
TI  - Process and outcomes of school nurse case management for students with asthma.
AB  - There have been many studies that have examined the impact of school-based asthma
      programs on students with asthma. However, most studies do not provide adequate
      elaboration on the components of the program. Therefore, replication of these
      programs is difficult. This study examines the process of school nurse case
      management, which includes the development of individualized goals and the
      provision of specific interventions. The process is then linked to several
      outcomes (parent perception, quality of life, and academic success). The study
      demonstrates the complexity of case management provided by school nurses and how
      goal attainment is related to the outcomes. The study supports policy
      recommendations that advocate for the importance of professional school nurses in
      improving the health and well-being of students with asthma. 

PMID- 24097970
TI  - Interstitial inflammation and long-term renal outcomes in lupus nephritis.
AB  - INTRODUCTION: The International Society of Nephrology/Renal Pathology Society
      (ISN/RPS) pathological classification criteria of lupus nephritis are limited to
      glomerular injury. Although the tubulointerstitium is commonly involved, the
      importance of such involvement is not well defined. The major objective of this
      study was to evaluate the association of interstitial inflammation with the long
      term outcomes of patients with lupus nephritis. PATIENTS AND METHODS: A total of
      73 patients who were diagnosed with lupus nephritis between 1996 and 2012 were
      analyzed. The follow-up data were obtained, and the analysis was conducted to
      determine the effect of interstitial inflammation on the rate of the doubling of
      serum creatinine or end-stage renal disease (ESRD) in patients with lupus
      nephritis. Of the patients included in the cohort, 63 underwent a second biopsy.
      RESULTS: The degree of interstitial inflammation was positively correlated with
      the serum creatinine level at the time of biopsy (p = 0.005) but not at the end
      of the follow-up period (p = 0.9). The complements level, anti-dsDNA, ANA, and
      proteinuria were not related to the degree of interstitial inflammation. There
      was no relationship between the probability of remission and the severity of
      interstitial infiltrate. The rate of no remission was 40% among those without
      interstitial infiltrate, 34.6% in those with mild infiltrate and 23.5% among
      those with moderate-to-severe infiltrate (p = 0.6). There was no relationship
      between interstitial inflammation at the baseline biopsy and worsening of renal
      function (p = 0.17). There was a strong relationship between interstitial
      inflammation at the repeat biopsy and renal survival (p = 0.005). The recovery of
      interstitial inflammation in lupus nephritis correlated with a favorable outcome
      in the patients with interstitial inflammation at baseline that had resolved at
      the repeated biopsy (p = 0.047). CONCLUSION: The persistence of interstitial
      inflammation is associated with poor renal outcome among patients with lupus
      nephritis. A comprehensive histological assessment of inflammation in lupus
      nephritis including interstitial inflammation may provide better prognostic
      information.

PMID- 24097971
TI  - Search for proteins required for accurate gene expression under oxidative stress:
      roles of guanylate kinase and RNA polymerase.
AB  - In aerobically growing cells, in which reactive oxygen species are produced, the
      guanine base is oxidized to 8-oxo-7,8-dihydroguanine, which can pair with adenine
      as well as cytosine. This mispairing causes alterations in gene expression, and
      cells possess mechanisms to prevent such outcomes. In Escherichia coli, 8-oxo-7,8
      dihydroguanine-related phenotypic suppression of lacZ amber is enhanced by
      mutations in genes related to the prevention of abnormal protein synthesis under
      oxidative stress. A genome-wide search for the genes responsible, followed by DNA
      sequence determination, revealed that specific amino acid changes in guanylate
      kinase and in the beta and beta' subunits of RNA polymerase cause elevated levels
      of phenotypic suppression, specifically under aerobic conditions. The involvement
      of the DnaB, DnaN, and MsbA proteins, which are involved in DNA replication and
      in preserving the membrane structure, was also noted. Interactions of these
      proteins with each other and also with other molecules may be important for
      preventing errors in gene expression. 

PMID- 24097972
TI  - During state 1 to state 2 transition in Arabidopsis thaliana, the photosystem II
      supercomplex gets phosphorylated but does not disassemble.
AB  - Plants are exposed to continuous changes in light quality and quantity that
      challenge the performance of the photosynthetic apparatus and have evolved a
      series of mechanisms to face this challenge. In this work, we have studied state
      transitions, the process that redistributes the excitation pressure between
      photosystems I and II (PSI/PSII) by the reversible association of LHCII, the
      major antenna complex of higher plants, with either one of them upon
      phosphorylation/dephosphorylation. By combining biochemical analysis and electron
      microscopy, we have studied the effect of state transitions on the composition
      and organization of photosystem II in Arabidopsis thaliana. Two LHCII trimers
      (called trimers M and S) are part of the PSII supercomplex, whereas up to two
      more are loosely associated with PSII in state 1 in higher plants (called "extra"
      trimers). Here, we show that the LHCII from the extra pool migrates to PSI in
      state 2, thus leaving the PSII supercomplex and the semicrystalline PSII arrays
      intact. In state 2, not only is the mobile LHCII phosphorylated, but also the
      LHCII in the PSII supercomplexes. This demonstrates that PSII phosphorylation is
      not sufficient for disconnecting LHCII trimers S and M from PSII and for their
      migration to PSI. 

PMID- 24097973
TI  - Heme oxygenase-1 exerts a protective role in ovalbumin-induced neutrophilic
      airway inflammation by inhibiting Th17 cell-mediated immune response.
AB  - Allergic asthma is conventionally considered as a Th2 immune response
      characterized by eosinophilic inflammation. Recent investigations revealed that
      Th17 cells play an important role in the pathogenesis of non-eosinophilic asthma
      (NEA), resulting in steroid-resistant neutrophilic airway inflammation. Heme
      oxygenase-1 (HO-1) has anti-inflammation, anti-oxidation, and anti-apoptosis
      functions. However, its role in NEA is still unclear. Here, we explore the role
      of HO-1 in a mouse model of NEA. HO-1 inducer hemin or HO-1 inhibitor tin
      protoporphyrin IX was injected intraperitoneally into ovalbumin-challenged
      DO11.10 mice. Small interfering RNA (siRNA) was delivered into mice to knock down
      HO-1 expression. The results show that induction of HO-1 by hemin attenuated
      airway inflammation and decreased neutrophil infiltration in bronchial alveolar
      lavage fluid and was accompanied by a lower proportion of Th17 cells in
      mediastinal lymph nodes and spleen. More importantly, induction of HO-1 down
      regulated Th17-related transcription factor retinoic acid-related orphan receptor
      gammat (RORgammat) expression and decreased IL-17A levels, all of which
      correlated with a decrease in phosphorylated STAT3 (p-STAT3) level and inhibition
      of Th17 cell differentiation. Consistently, the above events could be reversed by
      tin protoporphyrin IX. Also, HO-1 siRNA transfection abolished the effect of
      hemin induced HO-1 in vivo. Meanwhile, the hemin treatment promoted the level of
      Foxp3 expression and enhanced the proportion of regulatory T cells (Tregs).
      Collectively, our findings indicate that HO-1 exhibits anti-inflammatory activity
      in the mouse model of NEA via inhibition of the p-STAT3-RORgammat pathway,
      regulating kinetics of RORgammat and Foxp3 expression, thus providing a possible
      novel therapeutic target in asthmatic patients. 

PMID- 24097974
TI  - Human ovarian cancer stroma contains luteinized theca cells harboring tumor
      suppressor gene GT198 mutations.
AB  - Ovarian cancer is a highly lethal gynecological cancer, and its causes remain to
      be understood. Using a recently identified tumor suppressor gene, GT198
      (PSMC3IP), as a unique marker, we searched for the identity of GT198 mutant cells
      in ovarian cancer. GT198 has germ line mutations in familial and early onset
      breast and ovarian cancers and recurrent somatic mutations in sporadic fallopian
      tube cancers. GT198 protein has been shown as a steroid hormone receptor
      coregulator and also as a crucial factor in DNA repair. In this study, using
      GT198 as a marker for microdissection, we find that ovarian tumor stromal cells
      harboring GT198 mutations are present in various types of ovarian cancer
      including high and low grade serous, endometrioid, mucinous, clear cell, and
      granulosa cell carcinomas and in precursor lesions such as inclusion cysts. The
      mutant stromal cells consist of a luteinized theca cell lineage at various
      differentiation stages including CD133(+), CD44(+), and CD34(+) cells, although
      the vast majority of them are differentiated overexpressing steroidogenic enzyme
      CYP17, a theca cell-specific marker. In addition, wild type GT198 suppresses
      whereas mutant GT198 protein stimulates CYP17 expression. The chromatin-bound
      GT198 on the human CYP17 promoter is decreased by overexpressing mutant GT198
      protein, implicating the loss of wild type suppression in mutant cells. Together,
      our results suggest that GT198 mutant luteinized theca cells overexpressing CYP17
      are common in ovarian cancer stroma. Because first hit cancer gene mutations
      would specifically mark cancer-inducing cells, the identification of mutant
      luteinized theca cells may add crucial evidence in understanding the cause of
      human ovarian cancer. 

PMID- 24097975
TI  - Distinct specificity and single-molecule kinetics characterize the interaction of
      pathogenic and non-pathogenic antibodies against platelet factor 4-heparin
      complexes with platelet factor 4.
AB  - Heparin-induced thrombocytopenia (HIT) is a thrombotic complication of heparin
      therapy mediated by antibodies to complexes between platelet factor 4 (PF4) and
      heparin or cellular glycosaminoglycans. However, only a fraction of patients with
      anti-PF4-heparin antibodies develop HIT, implying that only a subset of these
      antibodies is pathogenic. The basis for the pathogenic potential of anti-PF4
      heparin antibodies remains unclear. To elucidate the intrinsic PF4-binding
      properties of HIT-like monoclonal antibody (KKO) versus non-pathogenic antibody
      (RTO) at the single-molecule level, we utilized optical trap-based force
      spectroscopy to measure the strength and probability of binding of surface
      attached antibodies with oligomeric PF4 to simulate interactions on cells. To
      mimic the effect of heparin in bringing PF4 complexes into proximity, we
      chemically cross-linked PF4 tetramers using glutaraldehyde. Analysis of the force
      histograms revealed that KKO-PF4 interactions had ~10-fold faster on-rates than
      RTO-PF4, and apparent equilibrium dissociation constants differed ~10-fold with
      similar force-free off-rates (k(off) = 0.0031 and 0.0029 s(-1)). Qualitatively
      similar results were obtained for KKO and RTO interacting with PF4-heparin
      complexes. In contrast to WT PF4, KKO and RTO showed lower and similar binding
      probabilities to cross-linked PF4(K50E), which forms few if any oligomers. Thus,
      formation of stable PF4 polymers results in much stronger interactions with the
      pathogenic antibody without a significant effect on the binding of the non
      pathogenic antibody. These results suggest a fundamental difference in the
      antigen-binding mechanisms between model pathogenic and non-pathogenic anti-PF4
      antibodies that might underlie their distinct pathophysiological behaviors.

PMID- 24097976
TI  - Protease-activated receptor 1 (PAR1) and PAR4 heterodimers are required for PAR1
      enhanced cleavage of PAR4 by alpha-thrombin.
AB  - Thrombin is a potent platelet agonist that activates platelets and other cells of
      the cardiovascular system by cleaving its G-protein-coupled receptors, protease
      activated receptor 1 (PAR1), PAR4, or both. We now show that cleaving PAR1 and
      PAR4 with alpha-thrombin induces heterodimer formation. PAR1-PAR4 heterodimers
      were not detected when unstimulated; however, when the cells were stimulated with
      10 nm alpha-thrombin, we were able to detect a strong interaction between PAR1
      and PAR4 by bioluminescence resonance energy transfer. In contrast, activating
      the receptors without cleavage using PAR1 and PAR4 agonist peptides (TFLLRN and
      AYPGKF, respectively) did not enhance heterodimer formation. Preventing PAR1 or
      PAR4 cleavage with point mutations or hirugen also prevented the induction of
      heterodimers. To further characterize the PAR1-PAR4 interactions, we mapped the
      heterodimer interface by introducing point mutations in transmembrane helix 4 of
      PAR1 or PAR4 that prevented heterodimer formation. Finally, we show that
      mutations in PAR1 or PAR4 at the heterodimer interface prevented PAR1-assisted
      cleavage of PAR4. These data demonstrate that PAR1 and PAR4 require allosteric
      changes induced via receptor cleavage by alpha-thrombin to mediate heterodimer
      formation, and we have determined the PAR1-PAR4 heterodimer interface. Our
      findings show that PAR1 and PAR4 have dynamic interactions on the cell surface
      that should be taken into account when developing and characterizing PAR
      antagonists. 

PMID- 24097977
TI  - Interaction of Shiga toxin with the A-domains and multimers of von Willebrand
      Factor.
AB  - Shiga toxin (Stx) produced by enterohemorrhagic Escherichia coli causes diarrhea
      associated hemolytic-uremic syndrome (DHUS), a severe renal thrombotic
      microangiopathy. We investigated the interaction between Stx and von Willebrand
      Factor (VWF), a multimeric plasma glycoprotein that mediates platelet adhesion,
      activation, and aggregation. Stx bound to ultra-large VWF (ULVWF) secreted from
      and anchored to stimulated human umbilical vein endothelial cells, as well as to
      immobilized VWF-rich human umbilical vein endothelial cell supernatant. This Stx
      binding was localized to the A1 and A2 domain of VWF monomeric subunits and
      reduced the rate of ADAMTS-13-mediated cleavage of the Tyr(1605)-Met(1606)
      peptide bond in the A2 domain. Stx-VWF interaction and the associated delay in
      ADAMTS-13-mediated cleavage of VWF may contribute to the pathophysiology of DHUS.

PMID- 24097978
TI  - Crystal and solution studies of the "Plus-C" odorant-binding protein 48 from
      Anopheles gambiae: control of binding specificity through three-dimensional
      domain swapping.
AB  - Much physiological and behavioral evidence has been provided suggesting that
      insect odorant-binding proteins (OBPs) are indispensable for odorant recognition
      and thus are appealing targets for structure-based discovery and design of novel
      host-seeking disruptors. Despite the fact that more than 60 putative OBP-encoding
      genes have been identified in the malaria vector Anopheles gambiae, the crystal
      structures of only six of them are known. It is therefore clear that OBP
      structure determination constitutes the bottleneck for structure-based approaches
      to mosquito repellent/attractant discovery. Here, we describe the three
      dimensional structure of an A. gambiae "Plus-C" group OBP (AgamOBP48), which
      exhibits the second highest expression levels in female antennae. This structure
      represents the first example of a three-dimensional domain-swapped dimer in
      dipteran species. A combined binding site is formed at the dimer interface by
      equal contribution of each monomer. Structural comparisons with the monomeric
      AgamOBP47 revealed that the major structural difference between the two Plus-C
      proteins localizes in their N- and C-terminal regions, and their concerted
      conformational change may account for monomer-swapped dimer conversion and
      furthermore the formation of novel binding pockets. Using a combination of gel
      filtration chromatography, differential scanning calorimetry, and analytical
      ultracentrifugation, we demonstrate the AgamOBP48 dimerization in solution.
      Eventually, molecular modeling calculations were used to predict the binding mode
      of the most potent synthetic ligand of AgamOBP48 known so far, discovered by
      ligand- and structure-based virtual screening. The structure-aided identification
      of multiple OBP binders represents a powerful tool to be employed in the effort
      to control transmission of the vector-borne diseases. 

PMID- 24097979
TI  - Inositol 1,4,5-trisphosphate (IP3) receptor up-regulation in hypertension is
      associated with sensitization of Ca2+ release and vascular smooth muscle
      contractility.
AB  - Resistance arteries show accentuated responsiveness to vasoconstrictor agonists
      in hypertension, and this abnormality relies partly on enhanced Ca(2+) signaling
      in vascular smooth muscle (VSM). Although inositol 1,4,5-triphosphate receptors
      (IP3Rs) are abundant in VSM, their role in the molecular remodeling of the Ca(2+)
      signaling machinery during hypertension has not been addressed. Therefore, we
      compared IP3R expression and function between mesenteric arteries of normotensive
      and hypertensive animals. Levels of IP3R transcript and protein were
      significantly increased in mesenteric arteries of hypertensive animals, and
      pharmacological inhibition of the IP3R revealed a higher contribution of IP3
      dependent Ca(2+) release to vascular contraction in these arteries. Subsequently,
      we established cultured aortic VSM A7r5 cells as a cellular model that replicates
      IP3R up-regulation during hypertension by depolarizing the VSM cell membrane.
      IP3R up-regulation requires Ca(2+) influx through L-type Ca(2+) channels,
      followed by activation of the calcineurin-NFAT axis, resulting in IP3R
      transcription. Functionally, IP3R up-regulation in VSM is associated with
      enhancement and sensitization of IP3-dependent Ca(2+) release, resulting in
      increased VSM contraction in response to agonist stimulation. 

PMID- 24097980
TI  - Analysis of hyperekplexia mutations identifies transmembrane domain
      rearrangements that mediate glycine receptor activation.
AB  - Pentameric ligand-gated ion channels (pLGICs) mediate numerous physiological
      processes and are therapeutic targets for a wide range of clinical indications.
      Elucidating the structural differences between their closed and open states may
      help in designing improved drugs that bias receptors toward the desired
      conformational state. We recently showed that two new hyperekplexia mutations,
      Q226E and V280M, induced spontaneous activity in alpha1 glycine receptors. Gln
      226, located near the top of transmembrane (TM) 1, is closely apposed to Arg-271
      at the top of TM2 in the neighboring subunit. Using mutant cycle analysis, we
      inferred that Q226E induces activation via an enhanced electrostatic attraction
      to Arg-271. This would tilt the top of TM2 toward TM1 and hence away from the
      pore axis to open the channel. We also concluded that the increased side chain
      volume of V280M, in the TM2-TM3 loop, exerts a steric repulsion against Ile-225
      at the top of TM1 in the neighboring subunit. We infer that this steric repulsion
      would tilt the top of TM3 radially outwards against the stationary TM1 and thus
      provide space for TM2 to relax away from the pore axis to create an open channel.
      Because the transmembrane domain movements inferred from this functional analysis
      are consistent with the structural differences evident in the x-ray atomic
      structures of closed and open state bacterial pLGICs, we propyose that the model
      of pLGIC activation as outlined here may be broadly applicable across the
      eukaryotic pLGIC receptor family. 

PMID- 24097981
TI  - Differential phospholipid substrates and directional transport by ATP-binding
      cassette proteins ABCA1, ABCA7, and ABCA4 and disease-causing mutants.
AB  - ABCA1, ABCA7, and ABCA4 are members of the ABCA subfamily of ATP-binding cassette
      transporters that share extensive sequence and structural similarity. Mutations
      in ABCA1 cause Tangier disease characterized by defective cholesterol homeostasis
      and high density lipoprotein (HDL) deficiency. Mutations in ABCA4 are responsible
      for Stargardt disease, a degenerative disorder associated with severe loss in
      central vision. Although cell-based studies have implicated ABCA proteins in
      lipid transport, the substrates and direction of transport have not been firmly
      established. We have purified and reconstituted ABCA1, ABCA7, and ABCA4 into
      liposomes for fluorescent-lipid transport studies. ABCA1 actively exported or
      flipped phosphatidylcholine, phosphatidylserine, and sphingomyelin from the
      cytoplasmic to the exocytoplasmic leaflet of membranes, whereas ABCA7
      preferentially exported phosphatidylserine. In contrast, ABCA4 transported
      phosphatidylethanolamine in the reverse direction. The same phospholipids
      stimulated the ATPase activity of these ABCA transporters. The transport and
      ATPase activities of ABCA1 and ABCA4 were reduced by 25% in the presence of 20%
      cholesterol. Nine ABCA1 Tangier mutants and the corresponding ABCA4 Stargardt
      mutants showed significantly reduced phospholipid transport activity and
      subcellular mislocalization. These studies provide the first direct evidence for
      ABCA1 and ABCA7 functioning as phospholipid transporters and suggest that this
      activity is an essential step in the loading of apoA-1 with phospholipids for HDL
      formation. 

PMID- 24097982
TI  - Structural insights into functional overlapping and differentiation among myosin
      V motors.
AB  - Myosin V (MyoV) motors have been implicated in the intracellular transport of
      diverse cargoes including vesicles, organelles, RNA-protein complexes, and
      regulatory proteins. Here, we have solved the cargo-binding domain (CBD)
      structures of the three human MyoV paralogs (Va, Vb, and Vc), revealing subtle
      structural changes that drive functional differentiation and a novel redox
      mechanism controlling the CBD dimerization process, which is unique for the MyoVc
      subclass. Moreover, the cargo- and motor-binding sites were structurally
      assigned, indicating the conservation of residues involved in the recognition of
      adaptors for peroxisome transport and providing high resolution insights into
      motor domain inhibition by CBD. These results contribute to understanding the
      structural requirements for cargo transport, autoinhibition, and regulatory
      mechanisms in myosin V motors. 

PMID- 24097983
TI  - The structure of NtdA, a sugar aminotransferase involved in the kanosamine
      biosynthetic pathway in Bacillus subtilis, reveals a new subclass of
      aminotransferases.
AB  - NtdA from Bacillus subtilis is a sugar aminotransferase that catalyzes the
      pyridoxal phosphate-dependent equatorial transamination of 3-oxo-alpha-D-glucose
      6-phosphate to form alpha-D-kanosamine 6-phosphate. The crystal structure of NtdA
      shows that NtdA shares the common aspartate aminotransferase fold (Type 1) with
      residues from both monomers forming the active site. The crystal structures of
      NtdA alone, co-crystallized with the product alpha-D-kanosamine 6-phosphate, and
      incubated with the amine donor glutamate reveal three key structures in the
      mechanistic pathway of NtdA. The structure of NtdA alone reveals the internal
      aldimine form of NtdA with the cofactor pyridoxal phosphate covalently attached
      to Lys-247. The addition of glutamate results in formation of pyridoxamine
      phosphate. Co-crystallization with kanosamine 6-phosphate results in the
      formation of the external aldimine. Only alpha-D-kanosamine 6-phosphate is
      observed in the active site of NtdA, not the beta-anomer. A comparison of the
      structure and sequence of NtdA with other sugar aminotransferases enables us to
      propose that the VIbeta family of aminotransferases should be divided into
      subfamilies based on the catalytic lysine motif.

PMID- 24097984
TI  - Suppression of heregulin beta signaling by the single N-glycan deletion mutant of
      soluble ErbB3 protein.
AB  - Heregulin signaling is involved in various tumor proliferations and invasions;
      thus, receptors of heregulin are targets for the cancer therapy. In this study we
      examined the suppressing effects of extracellular domains of ErbB2, ErbB3, and
      ErbB4 (soluble ErbB (sErbB)) on heregulin beta signaling in human breast cancer
      cell line MCF7. It was found that sErbB3 suppresses ligand-induced activation of
      ErbB receptors, PI3K/Akt and Ras/Erk pathways most effectively; sErbB2 scarcely
      suppresses ligand-induced signaling, and sErbB4 suppresses receptor activation at
      ~10% efficiency of sErbB3. It was revealed that sErbB3 does not decrease the
      effective ligands but decreases the effective receptors. By using small
      interfering RNA (siRNA) for ErbB receptors, we determined that sErbB3 suppresses
      the heregulin beta signaling by interfering ErbB3-containing heterodimers
      including ErbB2/ErbB3. By introducing the mutation of N418Q to sErbB3, the
      signaling-inhibitory effects were increased by 2-3-fold. Moreover, the sErbB3
      N418Q mutant enhanced anticancer effects of lapatinib more effectively than the
      wild type. We also determined the structures of N-glycan on Asn-418. Results
      suggested that the N-glycan-deleted mutant of sErbB3 suppresses heregulin
      signaling via ErbB3-containing heterodimers more effectively than the wild type.
      Thus, we demonstrated that the sErbB3 N418Q mutant is a potent inhibitor for
      heregulin beta signaling. 

PMID- 24097985
TI  - Polyamines are critical for the induction of the glutamate decarboxylase
      dependent acid resistance system in Escherichia coli.
AB  - As part of our studies on the biological functions of polyamines, we have used a
      mutant of Escherichia coli that lacks all the genes for polyamine biosynthesis
      for a global transcriptional analysis on the effect of added polyamines. The most
      striking early response to the polyamine addition is the increased expression of
      the genes for the glutamate-dependent acid resistance system (GDAR) that is
      important for the survival of the bacteria when passing through the acid
      environment of the stomach. Not only were the two genes for glutamate
      decarboxylases (gadA and gadB) and the gene for glutamate-gamma-aminobutyrate
      antiporter (gadC) induced by the polyamine addition, but the various genes
      involved in the regulation of this system were also induced. We confirmed the
      importance of polyamines for the induction of the GDAR system by direct
      measurement of glutamate decarboxylase activity and acid survival. The effect of
      deletions of the regulatory genes on the GDAR system and the effects of
      overproduction of two of these genes were also studied. Strikingly,
      overproduction of the alternative sigma factor rpoS and of the regulatory gene
      gadE resulted in very high levels of glutamate decarboxylase and almost complete
      protection against acid stress even in the absence of any polyamines. Thus, these
      data show that a major function of polyamines in E. coli is protection against
      acid stress by increasing the synthesis of glutamate decarboxylase, presumably by
      increasing the levels of the rpoS and gadE regulators. 

PMID- 24097986
TI  - Restricted 5'-end gap repair of HIV-1 integration due to limited cellular dNTP
      concentrations in human primary macrophages.
AB  - HIV-1 proviral DNA integration into host chromosomal DNA is only partially
      completed by the viral integrase, leaving two single-stranded DNA gaps with 5'
      end mismatched viral DNA flaps. It has been inferred that these gaps are repaired
      by the cellular DNA repair machinery. Here, we investigated the efficiency of gap
      repair at integration sites in different HIV-1 target cell types. First, we found
      that the general gap repair machinery in macrophages was attenuated compared with
      that in dividing CD4(+) T cells. In fact, the repair in macrophages was heavily
      reliant upon host DNA polymerase beta (Pol beta). Second, we tested whether the
      poor dNTP availability found in macrophages is responsible for the delayed HIV-1
      proviral DNA integration in this cell type because the Km value of Pol beta is
      much higher than the dNTP concentrations found in macrophages. Indeed, with the
      use of a modified quantitative AluI PCR assay, we demonstrated that the elevation
      of cellular dNTP concentrations accelerated DNA gap repair in macrophages at HIV
      1 proviral DNA integration sites. Finally, we found that human monocytes, which
      are resistant to HIV-1 infection, exhibited severely restricted gap repair
      capacity due not only to the very low levels of dNTPs detected but also to the
      significantly reduced expression of Pol beta. Taken together, these results
      suggest that the low dNTP concentrations found in macrophages and monocytes can
      restrict the repair steps necessary for HIV-1 integration. 

PMID- 24097987
TI  - Inhibition of telomerase recruitment and cancer cell death.
AB  - Continued proliferation of human cells requires maintenance of telomere length,
      usually accomplished by telomerase. Telomerase is recruited to chromosome ends by
      interaction with a patch of amino acids (the TEL patch, for TPP1 glutamate (E)
      and leucine (L)-rich patch) on the surface of telomere protein TPP1. In previous
      studies, interruption of this interaction by mutation prevented telomere
      extension in HeLa cells, but the cell culture continued to grow. We now show that
      the telomerase inhibitor BIBR1532 acts together with TEL patch mutations to
      inhibit the growth of HeLa cell lines and that apoptosis is a prominent mechanism
      of death of these cells. Survivor cells take over the population beginning around
      40 days in culture. These cells no longer express the TEL patch mutant TPP1,
      apparently because of silencing of the expression cassette, a survival mechanism
      that would not be available to cancer cells. These results provide hope that
      inhibiting the binding of telomerase to the TEL patch of TPP1, perhaps together
      with a modest inhibition of the telomerase enzyme, could comprise an effective
      anticancer therapy for the ~90% of human tumors that are telomerase-positive. 

PMID- 24097988
TI  - Collaborative regulation of development but independent control of metabolism by
      two epidermis-specific transcription factors in Caenorhabditis elegans.
AB  - Cell fate specification is typically initiated by a master regulator, which is
      relayed by tissue-specific regulatory proteins (usually transcription factors)
      for further enforcement of cell identities, but how the factors are coordinated
      among each other to "finish up" the specification remains poorly understood.
      Caenorhabditis elegans epidermis specification is initiated by a master
      regulator, ELT-1, that activates its targets, NHR-25 and ELT-3, two epidermis
      specific transcription factors that are important for development but not for
      initial specification of epidermis, thus providing a unique paradigm for
      illustrating how the tissue-specific regulatory proteins work together to enforce
      cell fate specification. Here we addressed the question through contrasting
      genome-wide in vivo binding targets between NHR-25 and ELT-3. We demonstrate that
      the two factors bind discrete but conserved DNA motifs, most of which remain in
      proximity, suggesting formation of a complex between the two. In agreement with
      this, gene ontology analysis of putative target genes suggested differential
      regulation of metabolism but coordinated control of epidermal development between
      the two factors, which is supported by quantitative analysis of expression of
      their specific or common targets in the presence or absence of either protein.
      Functional validation of a subset of the target genes showed both activating and
      inhibitory roles of NHR-25 and ELT-3 in regulating their targets. We further
      demonstrated differential control of specification of AB and C lineage-derived
      epidermis. The results allow us to assemble a comprehensive gene network
      underlying C. elegans epidermis development that is likely to be widely used
      across species and provides insights into how tissue-specific transcription
      factors coordinate with one another to enforce cell fate specification initiated
      by its master regulator. 

PMID- 24097991
TI  - Lupus: the new diabetes. SLE and chronic disease management.

PMID- 24097989
TI  - A conserved protein motif is required for full modulatory activity of negative
      elongation factor subunits NELF-A and NELF-B in modifying glucocorticoid receptor
      regulated gene induction properties.
AB  - NELF-B is a BRCA1-interacting protein and subunit (with NELF-A, -C/D, and -E) of
      the human negative elongation factor (NELF) complex, which participates in RNA
      polymerase II pausing shortly after transcription initiation, especially for
      synchronized gene expression. We now report new activities of NELF-B and other
      NELF complex subunits, which are to attenuate glucocorticoid receptor (GR)
      mediated gene induction, reduce the partial agonist activity of an antagonist,
      and increase the EC50 of an agonist during nonsynchronized expression of
      exogenous and endogenous reporters. Stable knockdown of endogenous NELF-B has the
      opposite effects on an exogenous gene. The GR ligand-binding domain suffices for
      these biological responses. ChIP assays reveal that NELF-B diminishes GR
      recruitment to promoter regions of two endogenous genes. Using a new competition
      assay, NELF-A and NELF-B are each shown to act independently as competitive
      decelerators at two steps after the site of GR action and before or at the site
      of reporter gene activity. A common motif in each NELF was identified that is
      required for full activity of both NELF-A and NELF-B. These studies allow us to
      position the actions of two new modulators of GR-regulated transactivation, NELF
      A and NELF-B, relative to other factors in the overall gene induction sequence. 

PMID- 24097992
TI  - The development of genome-wide association studies and their application to
      complex diseases, including lupus.
AB  - In this review, we explain the motivation for carrying out genome-wide
      association studies (GWAS), contrasting the achievements of linkage-based
      experiments for Mendelian traits with the difficulties found when applying that
      type of experiment to complex diseases. We explain the technical and
      organizational developments that were required to make GWAS feasible, as well as
      some of the theoretical concerns that were raised during the design of these
      studies. We describe the impressive achievements of GWAS in lupus, and compare
      them with the experiences in three other genetically complex disorders:
      rheumatoid arthritis, type 1 diabetes and coronary heart disease. GWAS have been
      successful in identifying many new susceptibility loci for these four diseases,
      and have provided the motivation for novel immunological work. We conclude by
      describing preliminary steps that have been taken towards translating the results
      of GWAS into improvements in patient care, explaining some of the difficulties
      involved, as well as successes that have already been achieved. 

PMID- 24097993
TI  - Ethnicity in systemic lupus erythematosus (SLE): its influence on susceptibility
      and outcomes.
AB  - Ethnicity is a biological and a social construct which encompasses ancestral
      genes, cultural, geographic and socioeconomic characteristics shared within a
      population. It is clear that no homogeneous racial groups exist within the human
      race as demonstrated when examining ancestry informative markers. Both the
      genetic and non-genetic components of ethnicity exert influence in the expression
      and outcome of systemic lupus erythematosus (SLE), including disease activity,
      damage accrual, work disability and mortality. Although it is difficult to
      determine the extent to which the differences observed in these parameters are
      caused by genetic or non-genetic factors, early in the disease genetic factors
      seem to play a more important role as determinants of the differences observed
      between SLE patients from various ethnic groups. Over the course of the disease,
      non-genetic factors seem to play a more important role. By and large, SLE is more
      frequent and more severe with higher disease activity and more damage accrual in
      non-Caucasian populations (Hispanics, African descendants and Asians) than in
      Caucasians. To overcome these differences it is necessary to optimize health care
      access to disadvantaged populations and use innovative tools to increase disease
      awareness and improve treatment adherence. 

PMID- 24097990
TI  - A structural analysis of DNA binding by myelin transcription factor 1 double zinc
      fingers.
AB  - Myelin transcription factor 1 (MyT1/NZF2), a member of the neural zinc-finger
      (NZF) protein family, is a transcription factor that plays a central role in the
      developing central nervous system. It has also recently been shown that, in
      combination with two other transcription factors, the highly similar paralog
      MyT1L is able to direct the differentiation of murine and human stem cells into
      functional neurons. MyT1 contains seven zinc fingers (ZFs) that are highly
      conserved throughout the protein and throughout the NZF family. We recently
      presented a model for the interaction of the fifth ZF of MyT1 with a DNA sequence
      derived from the promoter of the retinoic acid receptor (RARE) gene. Here, we
      have used NMR spectroscopy, in combination with surface plasmon resonance and
      data-driven molecular docking, to delineate the mechanism of DNA binding for
      double ZF polypeptides derived from MyT1. Our data indicate that a two-ZF unit
      interacts with the major groove of the entire RARE motif and that both fingers
      bind in an identical manner and with overall two-fold rotational symmetry,
      consistent with the palindromic nature of the target DNA. Several key residues
      located in one of the irregular loops of the ZFs are utilized to achieve specific
      binding. Analysis of the human and mouse genomes based on our structural data
      reveals three putative MyT1 target genes involved in neuronal development. 

PMID- 24097994
TI  - Damage in lupus patients--what have we learned so far?
AB  - With the improvement of survival of systemic lupus erythematosus (SLE) patients,
      prevention of organ damage has become a major goal in the management of these
      patients. The need for a reliable tool for assessment of cumulative damage over
      time led to the development of the Systemic Lupus International Collaborating
      Clinics/American College of Rheumatology (SLICC/ACR) damage index (SDI) that
      allowed a standardized measurement of damage and facilitated research in the
      field. Damage accumulates over the course of the disease; however, some patients
      do not accrue any damage even after many years. Damage accrues at a higher rate
      among patients with more active disease, highlighting the importance of prompt
      control of disease manifestations. However, medications administered to control
      disease activity, particularly corticosteroids, can also result in organ damage,
      emphasizing the need for adjustment of these agents as soon as disease is under
      control. 

PMID- 24097995
TI  - Premature coronary heart disease in SLE: can we prevent progression?
AB  - Patients with systemic lupus erythematosus (SLE) have a higher prevalence of
      clinical and subclinical atherosclerosis compared with age- and sex-matched
      controls. Atherosclerosis progression is also accelerated in SLE, and coronary
      heart disease (CHD) is a major cause of morbidity and mortality. Traditional
      cardiovascular (CV) risk factors, including hypertension, diabetes mellitus or
      dyslipidemia, are more prevalent in SLE patients than in the general population,
      but they cannot fully account for accelerated atherosclerosis in SLE. In fact, a
      number of nontraditional risk factors have been identified, including disease
      activity, damage and various treatments. Preventive strategies for CHD are
      mandatory in SLE patients and should include giving up smoking; performing
      regular physical activity; managing metabolic abnormalities such as dyslipidemia,
      insulin resistance, and diabetes; treating persistent disease activity; and
      minimizing chronic exposure to corticosteroids. Low-dose aspirin, angiotensin
      converting enzyme (ACE) inhibitors, vitamin D supplementation, antimalarials and,
      when indicated, some immunosuppressants such as mycophenolate mofetil should also
      be considered. 

PMID- 24097996
TI  - Premature coronary heart disease in systemic lupus erythematosus: what risk
      factors do we understand?
AB  - Coronary heart disease (CHD) is a major cause of mortality in systemic lupus
      erythematosus (SLE). This 'accelerated atherosclerosis' is due to a combination
      of traditional risk factors such as hypertension and hyperlipidemia, and also
      disease-related factors such as chronic inflammation. Recent work has provided
      valuable insights into the relative contribution of various risk factors and also
      identified novel risk factors. An understanding of risk factors is fundamental to
      the prevention of CHD in SLE. In this review, we will discuss the role of risk
      factors for CHD in SLE and offer some strategies for their assessment and
      management. 

PMID- 24097997
TI  - Transient ischemic attack and stroke in systemic lupus erythematosus.
AB  - Ischemic stroke is increased in systemic lupus erythematosus (SLE) patients. The
      differential diagnosis of stroke in SLE is complex. Transient ischemic attack and
      ischemic stroke share pathophysiologic mechanisms, but prognosis may vary
      depending on severity and cause, and definitions are dependent on the timing and
      extent of the diagnostic evaluation. In SLE patients with a history of transient
      ischemic attacks, stroke occurred in 57%. Cerebrovascular events account for 20%
      to 30% of deaths in patients with SLE. In SLE, both disease-specific and
      traditional stroke risk factors are important. 

PMID- 24097998
TI  - SLE and metabolic syndrome.
AB  - Metabolic syndrome (MetS) is a recently defined clustering of cardiovascular risk
      factors associated with insulin resistance and an increased risk of future type
      II diabetes mellitus and cardiovascular disease (CVD). Systemic lupus
      erythematosus (SLE) patients have an increased prevalence of MetS and an
      increased prevalence of insulin resistance. Chronic inflammation may predispose
      to these complications in SLE and there is also evidence that corticosteroid
      therapy also contributes, although this finding has not been as consistent as
      would be predicted from the known metabolic effects of corticosteroids. MetS may
      represent a good model in which to begin to understand how SLE drives an
      increased risk of CVD. For now, the utility of identifying MetS in patients is to
      identify a subset in which more focused lifestyle interventions should be
      targeted and in whom medication review and adjustment (especially corticosteroid
      doses) should be considered to help modify future CVD risk. 

PMID- 24097999
TI  - Renoprotective strategies in lupus nephritis: beyond immunosuppression.
AB  - Lupus nephritis needs to be diagnosed promptly and treated specifically with
      appropriate immunosuppression. However, all patients with lupus nephritis have by
      definition chronic kidney disease (CKD) as they will have proteinuria with
      varying degrees of renal impairment. CKD requires careful additional management,
      not only to reduce the risk of progression to end-stage renal disease but also
      because it is probably the strongest risk for cardiovascular morbidity and
      mortality. This review focuses on the evidence underscoring strategies to prevent
      progression of CKD beyond the "simple" treatment of the lupus nephritis. The
      strategies include immaculate control of blood pressure, inhibition of the renin
      angiotensin system to reduce blood pressure and proteinuria, and the benefits of
      lifestyle modifications such as tackling smoking, obesity and exercise. We also
      review the literature on control of dyslipidaemias which, although clearly of
      cardiovascular benefit, provide less compelling data for offering renoprotection.
      We touch on the emerging area of the importance of controlling urate levels in
      protecting against progressive renal impairment. Finally, there is a reminder
      about the importance of considering the nephrotoxicity of all medications
      prescribed for patients with lupus nephritis - above all the need to avoid the
      use of non-steroidal anti-inflammatory drugs. Overall, the theme is that there is
      much more to the management of patients with lupus nephritis than "just" the
      nephritis - a multidisciplinary approach involving nephrologists as well as
      rheumatologists is more likely to provide the appropriate wider care required for
      all patients with lupus nephritis. 

PMID- 24098000
TI  - Pulmonary arterial hypertension in SLE: what do we know?
AB  - Pulmonary hypertension (PH) can occur at any time during the course of systemic
      lupus erythematosus (SLE), and can be independent of lupus disease activity in
      other systems. The pathogenesis of PH in SLE can be multifactorial, but pulmonary
      arterial hypertension (PAH) is the commonest cause of PH in SLE. The
      international PH registries have published that approximately 15% of connective
      tissue disease-associated PH is lupus related in their cohorts. As the symptoms
      of PH in SLE can be mild and non-specific in early stages, an increasing
      awareness of this devastating complication is essential for early diagnosis.
      Echocardiographic evaluation of several right heart variables in addition to
      systolic pulmonary artery pressure estimation reduces false positive rates for PH
      detection. Antiphospholipid antibodies may predict SLE-PAH. Prompt treatment of
      PAH with newer PAH therapy as well as immunosuppression can reduce morbidity and
      prolong survival. The survival in SLE-associated PAH is better compared with
      systemic sclerosis-associated PH but worse than idiopathic PAH. Pregnancy in SLE
      PAH can result in a fatal outcome, especially in severe and poorly controlled PH
      at onset. 

PMID- 24098001
TI  - Infection risk in systemic lupus erythematosus patients: susceptibility factors
      and preventive strategies.
AB  - Infection is one of the leading causes of morbidity and mortality in systemic
      lupus erythematosus (SLE). Bacterial infections are most frequent, followed by
      viral and fungal infections. The impaired cellular and humoral immune functions
      seen in patients with SLE are predisposing conditions, whilst disease activity,
      prednisone doses over 7.5-10 mg/day, high doses of methylprednisolone or
      cyclophosphamide are well-recognised risk factors for infection. The first six
      months after rituximab treatment and the use of more than three courses are also
      associated with an increased susceptibility for infection. It has not been
      established whether belimumab, azathioprine and mycophenolate mofetil increase
      the risk of serious infections. Most vaccines are effective and safe in SLE
      patients, although vaccination should be avoided during periods of active
      disease. Live virus vaccines are contraindicated for immunosuppressed patients.
      Influenza and pneumococcal vaccines are universally recommended. Tuberculosis
      prophylaxis should be considered in selected cases. Therefore, it is advisable
      not to exceed doses of 5 mg/day of prednisone in chronic treatment.
      Methylprednisolone and cyclophosphamide should be used in low-dose regimens.
      Antimalarials have a well-known protective role against infection, in addition to
      other beneficial properties, thus, hydroxychloroquine is recommended for all SLE
      patients where no contraindication exists. 

PMID- 24098002
TI  - The challenge of pregnancy for patients with SLE.
AB  - Pregnancy poses an important challenge for doctors looking after women with
      systemic lupus erythematosus. Knowledge about safety of medications, the effect
      of pregnancy on such disease, and vice versa, together with multidisciplinary
      team care, are basic cornerstones needed to provide the best obstetric and
      medical care to these women. Pre-conceptional counselling constitutes the ideal
      scenario where a patient's previous obstetric history, organ damage, disease
      activity, serological profile and additional medical history can be summarized.
      Important issues regarding medication adjustment, planned scans and visits, and
      main risks discussion should also be raised at this stage. Planned pregnancies
      lead to better outcomes for both mothers and babies. Close surveillance
      throughout pregnancy and the puerperium, and tailored management approach
      guarantee the highest rates of successful pregnancies in these women. 

PMID- 24098003
TI  - Children and adolescents with SLE: not just little adults.
AB  - Juvenile-onset systemic lupus erythematosus (JSLE) represents 15-20% of all SLE
      cases. Whilst features of this chronic complex multisystem autoimmune disorder
      are highly variable, children and adolescents generally present with a more
      severe illness than adults and accrue greater disease damage over time. JSLE has
      a less striking female preponderance and differs from the adult form in pattern
      of major organ manifestations. Corticosteroids are used in almost all children
      with JSLE along with the majority requiring additional immunosuppressive
      medications. Making the diagnosis early and optimizing disease control are
      essential to ensure that normal childhood and adolescent development is not
      impeded. In this young population, special consideration must be given to the
      long-term sequelae of the disease and treatment-related toxicity. There is a
      current lack of paediatric-specific controlled trials and treatment strategies
      are generally guided by adult data. The enormous psychological and social impact
      of the disease and its treatments upon the child or young person and their family
      necessitates a comprehensive, holistic, specialized multidisciplinary approach to
      managing JSLE. 

PMID- 24098004
TI  - Coping with SLE: just in case vs. just in time: nurse's perspective.
AB  - This paper considers the experiences of people with lupus in comparison with
      those with diabetes, and discusses the impact of lupus specialist nurses in
      information-giving and education under the guise of 'just in case' vs. 'just in
      time'. Now recognized as a difficult condition to diagnose, lupus can lead to
      significant worry and distress especially during delays to diagnosis and times of
      high disease activity. Providing appropriate, individualized information to
      people with lupus is embedded in specialist nursing practice and enables
      individuals to use the tools of self-management approaches in gaining control
      over everyday symptoms. 

PMID- 24098005
TI  - Practical guide to understanding Comparative Effectiveness Research (CER).
AB  - "Comparative effectiveness research" (CER) is not a new concept; however,
      recently it has been popularized as a method to develop scientifically sound
      actionable data by which patients, physicians, payers, and policymakers may make
      informed health care decisions. Fundamental to CER is that the comparative data
      are derived from large diverse populations of patients assembled from point-of
      care general primary care practices and that measured outcomes include patient
      value judgments. The challenge is to obtain scientifically valid data to be acted
      upon by decision-making stakeholders with potentially quite diversely different
      agenda. The process requires very thoughtful research designs modulated by
      complex statistical and analytic methods. This article is composed of a guiding
      narrative with an extensive set of tables outlining many of the details required
      in performing and understanding CER. It ends with short discussions of three
      example papers, limitations of the method, and how a practicing physician may
      view such reports. 

PMID- 24098011
TI  - Trehalose biosynthesis in Myxococcus xanthus under osmotic stress and during
      spore formation.
AB  - In Myxococcus xanthus, trehalose is synthesized in response to osmotic stress and
      during spore formation. Genome data analysis indicated that M. xanthus has five
      related enzymes involved in four trehalose synthesis pathways (OtsAB, TreYZ, TreT
      and TreS). Under osmotic conditions, the amount of trehalose in wild-type cells
      was increased quickly by the OtsAB pathway, and the otsAB mutant began to
      synthesize trehalose using the TreYZ pathway. Also, in comparison with the wild
      type strain, the otsAB and treZ mutants showed ~65% and 40% reductions in the
      levels of intracellular trehalose accumulation, respectively, after 42 h of
      treatment with NaCl. In starvation-induced development of the wild-type strain,
      OtsAB activity was detected at middle and late stages of fruiting body
      development, and TreYZ activity was also detected at a late stage of development.
      Accumulation levels of trehalose in otsAB and treZ mutants were ~30% and 65% of
      that of the wild-type strain after 7 days of development, respectively. Wild-type
      and mutant strains did not show TreT and TreS activities under osmotic stress and
      development conditions. These results suggested that the OtsAB pathway may play a
      major role in trehalose biosynthesis in M. xanthus cells, with the TreYZ pathway
      playing an auxiliary role. 

PMID- 24098006
TI  - Analysis of radiation-induced cell death in head and neck squamous cell carcinoma
      and rat liver maintained in microfluidic devices.
AB  - OBJECTIVE: The aim of this study was to investigate how head and neck squamous
      cell carcinoma (HNSCC) tissue biopsies maintained in a pseudo in vivo environment
      within a bespoke microfluidic device respond to radiation treatment. STUDY
      DESIGN: Feasibility study. SETTING: Tertiary referral center. SUBJECTS AND
      METHODS: Thirty-five patients with HNSCC were recruited, and liver tissue from 5
      Wistar rats was obtained. A microfluidic device was used to maintain the tissue
      biopsy samples in a viable state. Rat liver was used to optimize the methodology.
      HNSCC was obtained from patients with T1-T3 laryngeal or oropharyngeal SCC; N1-N2
      metastatic cervical lymph nodes were also obtained. Irradiation consisted of
      single doses of between 2 Gy and 40 Gy and a fractionated course of 5*2 Gy. Cell
      death was assessed in the tissue effluent using the soluble markers lactate
      dehydrogenase (LDH) and cytochrome c and in the tissue by immunohistochemical
      detection of cleaved cytokeratin18 (M30 antibody). RESULTS: A significant surge
      in LDH release was demonstrated in the rat liver after a single dose of 20 Gy; in
      HNSCC, it was seen after 40 Gy compared with the control. There was no
      significant difference in cytochrome c release after 5 Gy or 10 Gy. M30
      demonstrated a dose-dependent increase in apoptotic index for a given increase in
      single-dose radiotherapy. There was a significant increase in apoptotic index
      between 1*2 Gy and 5*2 Gy. CONCLUSION: M30 is a superior method compared with
      soluble markers in detecting low-dose radiation-induced cell death. This
      microfluidic technique can be used to assess radiation-induced cell death in
      HNSCC and therefore has the potential to be used to predict radiation response.

PMID- 24098012
TI  - Expression and structural characterization of anti-T-antigen single-chain
      antibodies (scFvs) and analysis of their binding to T-antigen by surface plasmon
      resonance and NMR spectroscopy.
AB  - T-antigen (Galbeta1-3GalNAcalpha-1-Ser/Thr), also known as Thomsen-Friedenreich
      antigen (TF antigen), is an oncofetal antigen commonly found in cancerous
      tissues. Availability of anti-T-antigen human antibodies could lead to the
      development of cancer diagnostics and therapeutics. Four groups of single-chain
      variable fragment (scFv) genes were previously isolated from a phage library
      (Matsumoto-Takasaki et al. (2009) Isolation and characterization of anti-T
      antigen single chain antibodies from a phage library. BioSci Trends 3:87-95.).
      Here, four anti-T-antigen scFv genes belonging to Group 1-4 were expressed and
      produced in a Drosophila S2 cell expression system. ELISA and surface plasmon
      resonance (SPR) analyses confirmed the binding activity of 1E8 scFv protein to
      various T-antigen presenting conjugates. NMR experiments provided evidence of the
      folded nature of the 1E8 scFv protein. ScFv-ligand contact was identified by STD
      NMR, indicating that the galactose unit of T-antigen at the non-reducing end was
      primarily recognized by 1E8 scFv. This thus provides direct evidence of T-antigen
      specificity. 

PMID- 24098014
TI  - Approach to the patient: role of dosimetric RAI Rx in children with DTC.
AB  - CONTEXT: Pediatric differentiated thyroid cancer (DTC) patients frequently
      present with lymph node and/or distant (lung) metastases. Such patients warrant
      an aggressive treatment consisting of surgical removal of all surgically
      accessible local metastases as well as further treatment with one or more courses
      of radioiodine therapy (RAI). It is still a subject of debate in literature how
      much I-131 should be administered to pediatric patients. Patients can either be
      given a fixed (possibly body weight adjusted) activity or a dosimetry based
      activity, which is often considerably higher. OBJECTIVE: Here, we will present a
      typical case of a pediatric patient who was treated using a dosimetric approach.
      Then we will discuss the basis of dosimetry and the procedures involved, followed
      by a discussion of when to use dosimetric RAI as well as the pros and cons of the
      various approaches in pediatric patients. RESULTS: In general, two opposite
      approaches to dosimetry exist: either the activity that is as high as safely
      administrable (AHASA) is determined based on the radiation exposure to the
      critical organs at risk (in pediatric patients these are the bone marrow and, in
      patients with lung metastases, the lungs), or a lesion-based approach in which
      the activity that is required to deliver a certain radiation dose to the
      metastatic lesion(s) is determined. CONCLUSION: Because the latter approach
      requires an accurate volumetry of the target lesion(s), which is not possible in
      children with disseminated pulmonary metastases, which are often not visible with
      morphologic imaging techniques, we advocate using the AHASA approach in children
      with extensive metastatic DTC.

PMID- 24098015
TI  - Requirement for mass spectrometry sex steroid assays in the Journal of Clinical
      Endocrinology and Metabolism.

PMID- 24098016
TI  - Unraveling the genetic predisposition to differentiated thyroid carcinoma.

PMID- 24098017
TI  - How understanding thyroid cancer in Belgium can help us mitigate the problem of
      increasing incidence.

PMID- 24098022
TI  - Non-diabetic hypoglycemia.

PMID- 24098023
TI  - External quality assessment of BRAF molecular analysis in melanoma.
AB  - The availability of BRAF inhibitors has given metastatic melanoma patients an
      effective new treatment choice and molecular testing to determine the presence or
      absence of a BRAF codon 600 mutation is pivotal in the clinical management of
      these patients. This molecular test must be performed accurately and
      appropriately to ensure that the patient receives the most suitable treatment in
      a timely manner. Laboratories have introduced such testing; however, some
      experience low sample throughput making it critical that an external quality
      assurance programme is available to help promote a high standard of testing,
      reporting and provide an educational aspect for BRAF molecular testing.
      Laboratories took part in three rounds of external quality assessment (EQA)
      during a 12-month period giving participants a measure of the accuracy of
      genotyping, clinical interpretation of the result and experience in testing a
      range of different samples. Formalin fixed paraffin embedded tissue sections from
      malignant melanoma patients were distributed to participants for BRAF molecular
      testing. The standard of testing was generally high but distribution of a
      mutation other than the most common, p.(Val600Glu), highlighted concerns with
      detection or reporting of the presence of rarer mutations. The main issues raised
      in the interpretation of the results were the importance of clear unambiguous
      interpretation of the result tailored to the patient and the understanding that
      the treatment is different from that given to other stratified medicine
      programmes. The variability in reporting and wide range of methodologies used
      indicate a continuing need for EQA in this field. 

PMID- 24098024
TI  - miR-181a is associated with poor clinical outcome in patients with colorectal
      cancer treated with EGFR inhibitor.
AB  - AIMS: miR-181a expression is frequently altered in different types of cancer.
      Members of the Wnt/beta-catenin signalling pathway, which is commonly altered in
      colorectal cancer (CRC), have been reported as molecular interaction partners of
      miR-181. However, the role of miR-181a expression in CRC and its ability to
      predict survival and response to agents targeting the epidermal growth factor
      receptor (EGFR) have not been explored yet. METHODS: In this study, we analysed
      80 patients with wild type KRAS CRC undergoing treatment with the EGFR-targeting
      monoclonal antibodies cetuximab and panitumumab for metastatic CRC. The KRAS
      mutational status was determined by pyrosequencing and miR-181a expression was
      measured by quantitative RT-PCR in CRC tumour tissue and corresponding non
      neoplastic colon tissue. The microRNA expression levels were correlated with
      clinicopathological characteristics. Cancer-specific survival was calculated by
      univariate and multivariate analyses, and progression-free survival (PFS) during
      treatment with EGFR-targeting agents was also evaluated. RESULTS: A low miR-181a
      expression level was associated with poor differentiation of CRC (p=0.04). A
      Kaplan-Meier curve showed a decreased survival time for patients with low miR
      181a expression (p=0.019). Low miR-181a expression was furthermore associated
      with poor PFS (p=0.015). CONCLUSIONS: In conclusion, our data suggest that the
      miR-181a expression level is associated with poor survival in patients with CRC.
      Furthermore, miR-181a expression might predict PFS in EGFR-targeted therapy.

PMID- 24098025
TI  - Thymosin beta4 was upregulated in recurred colorectal cancers.

PMID- 24098027
TI  - Global health and dental education: a tipping point?

PMID- 24098028
TI  - Results from a new global oral health course: a case study at one dental school.
AB  - To channel students' interest in global oral health and prepare them to respond
      adequately to the health effects of globalization as future practitioners, new
      courses in dental curricula may be needed. This article documents the results of
      Harvard School of Dental Medicine (HSDM)'s new course, Global Oral Health:
      Interdisciplinary Approaches. To the authors' knowledge, this is the first course
      of its kind in dental education. HSDM developed learning objectives for the
      course based on the literature, the training and experience of HSDM global health
      faculty, and the mission of the HSDM Global Health Initiative. Dental residents
      and public health students enrolled, and some dental students audited. The
      discussion-based critical thinking course examined the extensive relationship
      between oral health and global health, and concept development was determined by
      in-class participation. After taking the course, students' assessments of their
      global oral health knowledge increased on average 100 percent. Nearly all
      students reported that they were very likely to use the concepts of global oral
      health in their careers and that they would definitely recommend the course to
      others. This course model seems to have met the expectations of students and
      faculty, and its fundamentals appear to be readily transferrable to other dental
      schools. 

PMID- 24098029
TI  - Voluntourism and global health: preparing dental students for responsible
      engagement in international programs.
AB  - Harvard School of Dental Medicine (HSDM) estimates that nearly 25 percent of its
      predoctoral dental students have expressed an interest in global health,
      including traveling abroad to conduct research or to volunteer in a project. This
      article addresses the important differences between "voluntourism" (combined
      volunteering and tourism) and responsible engagement in global health, reports on
      a pilot workshop at HSDM to promote responsible volunteering, and provides a
      recommendation on how to address these issues in the context of a dental
      curriculum. The pilot Workshop for Ethical Volunteering in Global Health was
      designed as a discussion-based, interactive program that included lectures, small
      group activities, and personal reflection. The aim of the workshop was to provide
      students with a systematic approach to ethical volunteering, critically
      reflecting on their motivation and attitudes related to conventional models of
      volunteering and facilitating alignment with principles of global health.
      Students participated in an anonymous written survey at the start and the close
      of the workshop. After the workshop, survey results demonstrated a significant
      increase in understanding the value of applying principles of global health when
      volunteering in order to avoid negative and unintended impacts on communities.
      All of the students reported that the workshop influenced the way they view
      volunteering in dentistry. 

PMID- 24098030
TI  - Student perceptions about the mission of dental schools to advance global
      dentistry and philanthropy.
AB  - In this study, 491 dental students at one dental school in the United States and
      one in Bulgaria were surveyed to assess their perceptions about the mission of
      dental schools to advance global dentistry and philanthropy. The study included
      questions about prior involvement in charitable dental missions. Many respondents
      felt that their dental school does not advance global dentistry nor adequately
      teaches students the virtues of philanthropy and volunteerism. The majority
      agreed, however, that dental schools have a moral obligation to raise the level
      of oral health care worldwide and help underserved communities access basic
      dental care. They reported that an opportunity to spend a semester at a foreign
      dental school would enhance their dental education in ways that are not presently
      fulfilled; help them better understand cultural diversity; and teach them about
      philanthropy and volunteerism. In their opinion, international exchange programs
      that provide clinical rotations and field experiences in economically challenged
      and underserved areas of the world would a) foster the global advancement of
      dentistry; b) promote an appreciation for cultural diversity and socioeconomic
      disparity in the communities that graduates will be serving; and c) teach
      students the virtues of philanthropy and volunteerism. This study may contribute
      to understanding factors affecting student involvement in programs to advance
      global dentistry. 

PMID- 24098031
TI  - Geriatrics education in U.S. dental schools: where do we stand, and what
      improvements should be made?
AB  - The number of adults above sixty-five years of age in the United States will
      expand considerably over the next thirty years. However, many dentists believe
      that their dental education did not adequately prepare them to treat an older
      adult population. Consequently, it is important to review dental curricula to
      determine where these gaps in education may occur and what can be done to address
      them in order to improve access to care. In this study, information was gathered
      from the websites of sixty-two U.S. dental schools in order to understand the
      types of geriatric courses offered. This review revealed that while most schools
      (89 percent) provide their predoctoral students with some education in
      geriatrics, only fourteen (22.6 percent) offer clinical training specifically for
      older adult care. In addition, forty-three schools (69 percent) include a
      geriatric component in either their General Practice Residency or Advanced
      Education in General Dentistry programs or have a certificate program in
      geriatric dentistry. Only about 23 percent of the schools offer a continuing
      education course in geriatrics at any one time. Previous studies have shown that
      clinical training is the most effective method of increasing students' confidence
      in treating older patients. Consequently, dental schools should work to
      incorporate clinical experience into geriatric education to prevent widening an
      existing gap in older adult oral health care. 

PMID- 24098032
TI  - Evidence-based dentistry and clinical implementation by third-year dental
      students.
AB  - Over the last two decades, the concept of evidence-based medicine (EBM) has
      become the standard of medical care. Defined by Sackett et al. as "the
      conscientious, explicit, and judicious use of current best evidence in making
      decisions about the care of individual patients," EBM recognizes that the
      practitioner should combine individual clinical expertise with the best available
      external evidence for optimal care. Consideration of the patient's needs and
      preferences is also an integral component of the clinical application. Dental
      educators have to account for the fact that not all dental treatment outcomes
      have been researched with randomized clinical trials. Dogmas in dentistry still
      exist regarding restorative treatments and methods taught to next generations of
      practitioners, while limited evidence is available. The purpose of this study was
      to determine how third-year dental students at one U.S. dental school select
      articles to provide supportive evidence related to treatment planning. The
      results show that knowledge provided in a three-week course in evidence-based
      dentistry (EBD) for first-year dental students was not efficiently applied when
      the students reached their third year. A significant percentage of the students
      perceived the use of literature as not beneficial for sustaining clinical aspects
      of a treatment plan, and they did not use appropriate tools to access best
      available resources. As a result of these findings, the article proposes
      incorporation of specific learning objectives related to EBD principles
      throughout the curriculum and a simplified method to search for best available
      evidence that has the advantage of not requiring knowledge and training in
      rigorous formulation of clinical questions. 

PMID- 24098033
TI  - An overview of case-based and problem-based learning methodologies for dental
      education.
AB  - Dental education has undergone significant curriculum reform in response to the
      1995 Institute of Medicine report Dental Education at the Crossroads and the
      series of white papers from the American Dental Education Association Commission
      on Change and Innovation in Dental Education (ADEA CCI) first published in the
      Journal of Dental Education and subsequently collected in a volume titled Beyond
      the Crossroads: Change and Innovation in Dental Education. An important element
      of this reform has been the introduction into academic dentistry of active
      learning strategies such as problem-based and case-based learning. As an aide to
      broadening understanding of these approaches in order to support their expansion
      in dental education, this article reviews the major characteristics of each
      approach, situates each in adult learning theory, and discusses the advantages of
      case-based learning in the development of a multidisciplinary, integrated
      predoctoral dental curriculum. 

PMID- 24098034
TI  - Teaching atraumatic restorative treatment in U.S. dental schools: a survey of
      predoctoral pediatric dentistry program directors.
AB  - The International Dental Federation and World Health Organization have promoted
      the use of Atraumatic Restorative Treatment (ART) in modern clinical settings
      worldwide. In the United States, the practice of ART is not believed to be widely
      used, which may be a result of little attention given to ART training in
      predoctoral pediatric dentistry curricula in U.S. dental schools. This study
      investigated the extent of clinical and didactic instruction on ART provided in
      U.S. dental schools by surveying the predoctoral pediatric dentistry programs in
      2010. Of the fifty-seven directors asked to complete the survey, forty-four
      responded for a response rate of 77 percent. Of these forty-four programs, 66
      percent reported providing clinical training on ART, though only 14 percent
      provide this training often or very often. The types of ART training provided
      often or very often included interim treatment (18 percent) and single-surface
      cavities (14 percent) in primary teeth. However, ART was said to be rarely taught
      as a definitive treatment in permanent teeth (2 percent). Attitude was a major
      predictor, for clinical training provided and using professional guidelines in
      treatment decisions were associated with a positive attitude towards ART. These
      predoctoral pediatric dentistry programs used ART mainly in primary, anterior,
      and single-surface cavities and as interim treatment. As ART increases access of
      children to dental care, the incorporation of the ART approach into the curricula
      of U.S. dental schools should be facilitated by professional organizations. 

PMID- 24098035
TI  - Triple jump examinations for dental student assessment.
AB  - The triple jump examination (TJE) attempts to assess a higher level of learning
      with demand for analysis, critical thinking, and resolution of problems presented
      by written scenarios based on patient care situations. The purpose of this study
      was to examine the internal consistency, scale reliability, and interrater
      reliability of the TJE used at the Ostrow School of Dentistry, University of
      Southern California. On the sample of 2,227 examinations administered by seventy
      seven raters across a three-year time period, the Cronbach's coefficient alpha
      for internal consistency of the overall TJE was found to be good (a=0.869). The
      internal consistency of the three subscales was found to be acceptable (a=0.731),
      good (a=0.820), and good (a=0.820). Average and single measures intraclass
      correlation coefficients (ICC) for scale reliability were significant at p<0.001,
      indicating strong interrater reliability. There were no statistically significant
      differences (p<=0.05) in the mean scores assigned on the TJE between rater groups
      defined by rater experience level with the TJE. A very high level of agreement
      among rater pairs was also observed. Across the entire three-year study period,
      with over 19,152 ratings, the seventy-seven raters were in general agreement 99.5
      percent of the time and in exact agreement 77.2 percent of the time. 

PMID- 24098036
TI  - Student evaluation of clickers in a combined dental and dental hygiene
      periodontology course.
AB  - The purpose of this report is to describe the general use of clickers as an
      active learning tool and how they were used in teaching a combined periodontology
      course for second-year dental and junior dental hygiene students. A survey was
      used to capture student perceptions following completion of the course. Specific
      domains were active learning, improved performance, and expectations. The survey
      response rate was 94.5 percent (121/128). Descriptive analyses showed that, in
      the domain of active learning, 102 (84.3 percent) agreed/strongly agreed that the
      use of clickers made the lectures more interactive; sixty-six (54.5 percent)
      agreed/strongly agreed that the clickers made them focus; and ninety-two (76
      percent) agreed/strongly agreed that the clickers encouraged active
      participation. In the domain regarding improved performance, sixty-three (52
      percent) agreed/ strongly agreed that the review sessions utilizing clickers
      helped them prepare for tests. In the domain of expectations, ninety-three (76.9
      percent) had a better idea of what to expect on the examination due to the use of
      clickers, and seventy-three (60.3 percent) thought that the clickers should be
      used in future semesters for this class. In addition, faculty members appreciated
      the greater participation afforded through the use of clickers to obtain a better
      understanding of the students' grasp of course content. Learning theory suggests
      that students must actively engage in the learning process in order for
      meaningful learning in the form of critical thinking and problem-solving to take
      place. In this study, students confirmed that the use of clicker technology
      encouraged their active participation in a periodontology course. 

PMID- 24098037
TI  - Current cariology education in dental schools in Spanish-speaking Latin American
      countries.
AB  - This study sought to provide an overview of current cariology education in
      Spanish-speaking Latin American dental schools. Data collection was via an
      eighteen-item survey with questions about curriculum, methods of diagnosis and
      treatment, and instructors' perceptions about cariology teaching. The response
      rate was 62.1 percent (n=54), and distribution of participating schools by
      country was as follows: Bolivia (four), Chile (four), Colombia (twenty-four),
      Costa Rica (one), Cuba (one), Dominican Republic (two), El Salvador (two), Mexico
      (six), Panama (two), Peru (four), Puerto Rico (one), Uruguay (two), and Venezuela
      (one). Forty percent of the responding schools considered cariology the key axis
      of a course, with a cariology department in 16.7 percent. All schools reported
      teaching cariology, but with varying hours and at varying times in the
      curriculum, and 77.8 percent reported having preclinical practices. The majority
      reported teaching most main teaching topics, except for behavioral sciences,
      microbiology, saliva and systemic diseases, caries-risk factors, root caries,
      erosion, and early caries management strategies. The most frequently taught
      caries detection methods were visual-tactile (96.3 percent), radiographic (92.6
      percent), and the International Caries Detection and Assessment System (ICDAS)
      (61.1 percent). Respondents said their schools' clinics make an operative
      treatment decision when radiolucency is in the inner half of enamel (42.3
      percent) for radiographic criteria and when the lesion is visually non-cavitated
      (5.8 percent). All respondents reported that their schools teach preventive
      strategies, but only 43.4 percent said they tie it to risk assessment and 40.7
      percent said they implement nonsurgical management regularly. 

PMID- 24098038
TI  - Sense of humor and its association with psychological disturbances among dental
      students in India.
AB  - Although the health benefits of humor and the potential advantages of having a
      good Sense of Humor (SoH) have been long recognized, they have not been
      investigated in dental students. The aim of this study was to assess the extent
      and demographic correlates of SoH in dental students and its association with
      their self-reported level of psychological disturbances. Six hundred and five
      students (age 20.3+/-1.83 years, 250 males, 355 females) from two dental schools
      in India anonymously completed the Multidimensional Sense of Humor Scale (MSHS)
      and the Depression Anxiety Stress Scales-21. Independent samples t-test and one
      way ANOVA were used to analyze the intergroup differences based on gender and
      year of study, respectively. The association between SoH and each of the three
      negative affective states was evaluated with multiple linear regressions. The
      mean MSHS score of the sample was 59.65+/-11.77. Male students showed a
      marginally higher SoH than females (60.78 vs. 58.86, p<0.05). The level of SoH
      steadily improved along the course duration, with statistically significant
      increases in the third and fifth years of study. SoH was negatively associated
      with all three negative affective states and explained nearly 3 to 5 percent of
      their variance. These results warrant further inquiry on the correlates of SoH in
      dental students, the psychosocial roles of humor, and their application in
      improving the psychological climate in dental schools. 

PMID- 24098039
TI  - Psychological well-being, health, and stress sources in Turkish dental students.
AB  - This study investigated the psychological well-being and overall health of a
      group of Turkish dental students and their sources of stress. Two hundred and
      seventy-seven students (57 percent female) from Gazi University Dental Faculty
      completed the Dental Environment Stress (DES) questionnaire, the Psychological
      General Well-Being (PGWB) index, and the SF-36 Health Survey. The results showed
      that the DES scores increased over the five-year period. Pressure to perform,
      faculty and administration, workload, and students' perceptions of their self
      efficacy were the most stress-provoking factors. Students whose first choice was
      dentistry experienced less stress and fewer health problems (p<0.05) than
      students whose first choice had not been dentistry. Psychological well-being and
      overall health were significantly associated with year of study. Statistically
      significant gender differences were observed on depressed mood and anxiety
      dimension scores of PGWB. Female students experienced greater stress than males,
      while male students had better overall health than females (p<0.01). Students who
      lived with their parents had lower PGWB scores (p<0.05). Age was significantly
      related with the DES and PGWB scores. These results found that stress among these
      Turkish dental students was influenced by gender, year of study, social
      background, and lifestyle. Based on the results of this study, recommendations
      can be made for changes in the dental education system in order to reduce stress
      among dental students especially during the last two years of study. 

PMID- 24098040
TI  - Knowledge of oral cancer among recently graduated medical and dental
      professionals in Amman, Jordan.
AB  - Oral cancer is a devastating disease, and despite advances in treatment, the
      survival rate remains low. Early diagnosis can improve survival and outcomes.
      Delayed referrals are often due to the inadequate knowledge of general health
      professionals. The aim of this study was to assess the knowledge of oral cancer
      among recently graduated dental and medical professionals interested in working
      in a cancer center in Amman, Jordan. The study was conducted using a
      questionnaire to assess the knowledge of risk factors and the ability to
      correctly identify the oral lesions most commonly associated with oral cancer. A
      total of 112 individuals completed the questionnaire. The results revealed an
      inadequate level of knowledge of oral cancer among the study population, with
      significant differences between the dental and medical professionals. This study
      suggests there is a need for improvement of the undergraduate curriculum in oral
      cancer in both medical and dental schools in Jordan and for the provision of
      postgraduate and continuing education on this topic. 

PMID- 24098041
TI  - Knowledge and attitudes of dental interns in Karnataka state, India, regarding
      implants.
AB  - Implant treatment today is highly reliable as a valid restorative option for
      missing teeth. As more patients worldwide opt for implant treatment, it is now
      imperative for dental practitioners to have sound information about dental
      implants so they can help patients make informed decisions. This study sought to
      define the knowledge and attitudes regarding dental implants of dental interns in
      the state of Karnataka, India, and to evaluate the dental implant curriculum
      structure at the undergraduate level. A survey was conducted of dental interns
      (students in their fifth, clinical year of undergraduate study) in seven of the
      forty-five academic dental institutions in this state. The questionnaire
      consisted of fifteen questions that assessed the respondents' level of knowledge
      and source of information regarding implants. A total of 500 questionnaires were
      distributed, and 417 interns responded for a response rate of 83.4 percent. In
      the results, 73.3 percent reported they were not provided sufficient information
      about implants in their undergraduate curriculum, and 95.7 percent of them wanted
      more. Also, 63.5 percent of the respondents believed that high costs could limit
      the use of dental implants as a tooth replacement modality in India. This study
      concludes that revision in the undergraduate dental curricula at these schools is
      needed to better prepare students for practicing implant dentistry. 

PMID- 24098042
TI  - Learning style preferences of first-year dental students at King Saud University
      in Riyadh, Saudi Arabia: influence of gender and GPA.
AB  - The aim of this study was to investigate the learning style preferences of a
      group of first-year dental students and their relation to gender and past
      academic performance. A total of 113 first-year dental students (forty-two
      female, seventy-one male) at King Saud University in Riyadh, Saudi Arabia,
      participated. The Visual, Aural, Read-write, and Kinesthetic (VARK) questionnaire
      was used to determine the students' preferred mode of learning. This sixteen-item
      questionnaire defines preference of learning based on the sensory modalities:
      visual, aural, reading/writing, and kinesthetic. More than half (59 percent) of
      the students were found to have multimodal learning preferences. The most common
      single learning preferences were aural (20 percent) followed by kinesthetic (15.2
      percent). Gender differences were not statistically significant. However, a
      statistically significant difference was found in the mean values of GPA in
      relation to the students' learning style preferences (p=0.019). Students with a
      single learning style preference had a lower mean GPA than those with multiple
      (quad-modal) learning style preferences. For effective instruction, dental
      educators need to broaden their range of presentation styles to help create more
      positive and effective learning environments for all students. 

PMID- 24098043
TI  - Attitudes of students and teachers on cheating behaviors: descriptive cross
      sectional study at six dental colleges in India.
AB  - Cheating behavior has been a serious problem in dental institutions across the
      globe. Attitudes of dental students have an impact on the quality of health care
      provided to their patients. This descriptive cross-sectional study had the
      following objectives: to assess and compare the attitudes of dental students and
      teachers about cheating behaviors, to assess students' opinions of various
      justifications for their cheating, and to assess teachers' attitudes towards
      various punishment options for cheating behaviors. The study sample consisted of
      1,261 undergraduate students and 131 teachers from six randomly chosen dental
      colleges in Tamil Nadu State, India. A closed-ended questionnaire was used for
      respondents to rate the seriousness of cheating behaviors. The students were
      asked to justify their cheating behavior, and the teachers were asked to assign
      punishments for the cheating behaviors. The attitudes of students and teachers on
      the cheating behaviors were analyzed and compared using a Pearson chisquare test,
      with a confidence interval of 95 percent and significance level of p<=0.05. The
      attitudes of the teachers and students were statistically different in two
      cheating behaviors: copying during exams and helping other students copy in
      exams. The two main justifying reasons students gave for cheating behavior were
      to pass the exam (59.3 percent) and to obtain a better grade (31.3 percent).
      Warning and counseling to help the students reassess their moral values were
      preferred to penalizing punishments by the teachers. 

PMID- 24098044
TI  - Nationwide survey of fifth-year dental students' perceptions about tobacco
      prevention, control, and curriculum in India.
AB  - The objective of this study was to assess the tobacco cessation knowledge,
      attitudes, practices, and perceived barriers of dental interns (students in their
      last year of the five-year dental curriculum) in India as well as to assess the
      adequacy of training in tobacco use cessation (TUC) counselling. This was a cross
      sectional questionnaire study conducted with 1,521 interns at fiftyone dental
      colleges of India selected by multistage random sampling. The survey instrument
      was a fifty-nine-item, self-structured, and self-administered questionnaire.
      Fifteen questions were about knowledge and attitudes, with twenty-two about
      practices, fifteen about barriers, and seven about curriculum adequacy;
      demographic data were also collected. The response rate was 99.7 percent. The
      results showed that 38.8 percent had knowledge, 30.8 percent had positive
      attitudes, 19.2 percent practiced TUC, 43 percent experienced barriers, and 85.2
      percent agreed on receiving extensive curriculum on tobacco cessation. Only 1
      percent were aware of the 5As, the 5Rs protocol, and the motivational
      interviewing technique of TUC. These respondents' knowledge, attitudes, and
      practices were below normative level, and they took a superficial approach to
      TUC. The perceived barriers were very high and included curriculum inadequacy.
      The results of this study help show there is an urgent need to revise the tobacco
      curriculum in dental schools in India to make students more confident to practice
      this aspect of dentistry independently. 

PMID- 24098045
TI  - Socioeconomic determinants of haemoglobin levels of African women are less
      important in areas with more health facilities: a multilevel analysis.
AB  - BACKGROUND: The prevalence of anaemia in Africa is the highest in the world.
      Especially women are at risk because of blood loss during menstruation and
      increased iron requirements during pregnancy. This study examined determinants of
      the haemoglobin (Hb) level of African women at individual/household, cluster,
      district, and national level. Special attention was paid to socioeconomic factors
      and the presence of health facilities. METHODS: Data were derived from
      Demographic and Health Surveys conducted between 2003 and 2010 in 21 African
      countries. We included all women aged 15-49 who participated in a women's survey
      and had a Hb measurement. Multilevel models were used to examine the influence of
      various factors at different hierarchical levels simultaneously. RESULTS: 104 899
      women were included in the study, of which 23.1% were anaemic (Hb<110 g/L).
      Socioeconomic factors were strongly related to the Hb level of women. Wealth,
      education, having a job, occupation of the partner, presence of a toilet
      facility, context educational level and preventive health measures were
      positively associated with the Hb level. Interaction analysis indicated that
      socioeconomic differences in the Hb level of women were reduced by the presence
      of health facilities. CONCLUSIONS: Interventions aimed at improving the Hb level
      of African women should take socioeconomic and contextual aspects into account.
      Increasing availability of health facilities might be a tool for reducing
      socioeconomic differences.

PMID- 24098046
TI  - Exploring the social determinants of mental health service use using
      intersectionality theory and CART analysis.
AB  - BACKGROUND: Fewer than half of individuals with a mental disorder seek formal
      care in a given year. Much research has been conducted on the factors that
      influence service use in this population, but the methods generally used cannot
      easily identify the complex interactions that are thought to exist. In this
      paper, we examine predictors of subsequent service use among respondents to a
      population health survey who met criteria for a past-year mood, anxiety or
      substance-related disorder. METHODS: To determine service use, we use an
      administrative database including all physician consultations in the period of
      interest. To identify predictors, we use classification tree (CART) analysis, a
      data mining technique with the ability to identify unsuspected interactions. We
      compare results to those from logistic regression models. RESULTS: We identify
      1213 individuals with past-year disorder. In the year after the survey, 24%
      (n=312) of these had a mental health-related physician consultation. Logistic
      regression revealed that age, sex and marital status predicted service use. CART
      analysis yielded a set of rules based on age, sex, marital status and income
      adequacy, with marital status playing a role among men and by income adequacy
      important among women. CART analysis proved moderately effective overall, with
      agreement of 60%, sensitivity of 82% and specificity of 53%. CONCLUSION: Results
      highlight the potential of data-mining techniques to uncover complex
      interactions, and offer support to the view that the intersection of multiple
      statuses influence health and behaviour in ways that are difficult to identify
      with conventional statistics. The disadvantages of these methods are also
      discussed.

PMID- 24098047
TI  - Ethylene is involved in strawberry fruit ripening in an organ-specific manner.
AB  - The fruit of the strawberry Fragaria*ananassa has traditionally been classified
      as non-climacteric because its ripening process is not governed by ethylene.
      However, previous studies have reported the timely endogenous production of minor
      amounts of ethylene by the fruit as well as the differential expression of genes
      of the ethylene synthesis, reception, and signalling pathways during fruit
      development. Mining of the Fragaria vesca genome allowed for the identification
      of the two main ethylene biosynthetic genes, 1-aminocyclopropane-1-carboxylic
      acid (ACC) synthase and ACC oxidase. Their expression pattern during fruit
      ripening was found to be stage and organ (achene or receptacle) specific.
      Strawberry plants with altered sensitivity to ethylene could be employed to
      unravel the role of ethylene in the ripening process of the strawberry fruit. To
      this end, independent lines of transgenic strawberry plants were generated that
      overexpress the Arabidopsis etr1-1 mutant ethylene receptor, which is a dominant
      negative allele, causing diminished sensitivity to ethylene. Genes involved in
      ethylene perception as well as in its related downstream processes, such as
      flavonoid biosynthesis, pectin metabolism, and volatile biosynthesis, were
      differently expressed in two transgenic tissues, the achene and the receptacle.
      The different transcriptional responsiveness of the achene and the receptacle to
      ethylene was also revealed by the metabolic profiling of the primary metabolites
      in these two organs. The free amino acid content was higher in the transgenic
      lines compared with the control in the mature achene, while glucose and fructose,
      and citric and malic acids were at lower levels. In the receptacle, the most
      conspicuous change in the transgenic lines was the depletion of the tricarboxylic
      acid cycle intermediates at the white stage of development, most probably as a
      consequence of diminished respiration. The results are discussed in the context
      of the importance of ethylene during strawberry fruit ripening. 

PMID- 24098048
TI  - Mercury-sensitive water channels as possible sensors of water potentials in
      pollen.
AB  - The growing pollen tube is central to plant reproduction and is a long-standing
      model for cellular tip growth in biology. Rapid osmotically driven growth is
      maintained under variable conditions, which requires osmosensing and regulation.
      This study explores the mechanism of water entry and the potential role of
      osmosensory regulation in maintaining pollen growth. The osmotic permeability of
      the plasmalemma of Lilium pollen tubes was measured from plasmolysis rates to be
      1.32+/-0.31*10(-3) cm s(-1). Mercuric ions reduce this permeability by 65%.
      Simulations using an osmotic model of pollen tube growth predict that an
      osmosensor at the cell membrane controls pectin deposition at the cell tip;
      inhibiting the sensor is predicted to cause tip bursting due to cell wall
      thinning. It was found that adding mercury to growing pollen tubes caused such a
      bursting of the tips. The model indicates that lowering the osmotic permeability
      per se does not lead to bursting but rather to thickening of the tip. The time
      course of induced bursting showed no time lag and was independent of mercury
      concentration, compatible with a surface site of action. The submaximal bursting
      response to intermediate mercuric ion concentration was independent of the
      concentration of calcium ions, showing that bursting is not due to a competitive
      inhibition of calcium binding or entry. Bursting with the same time course was
      also shown by cells growing on potassium-free media, indicating that potassium
      channels (implicated in mechanosensing) are not involved in the bursting
      response. The possible involvement of mercury-sensitive water channels as
      osmosensors and current knowledge of these in pollen cells are discussed. 

PMID- 24098049
TI  - Transcription factors, sucrose, and sucrose metabolic genes interact to regulate
      potato phenylpropanoid metabolism.
AB  - Much remains unknown about how transcription factors and sugars regulate
      phenylpropanoid metabolism in tuber crops like potato (Solanum tuberosum). Based
      on phylogeny and protein similarity to known regulators of phenylpropanoid
      metabolism, 15 transcription factors were selected and their expression was
      compared in white, yellow, red, and purple genotypes with contrasting phenolic
      and anthocyanin profiles. Red and purple genotypes had increased phenylalanine
      ammonia lyase (PAL) enzyme activity, markedly higher levels of phenylpropanoids,
      and elevated expression of most phenylpropanoid structural genes, including a
      novel anthocyanin O-methyltransferase. The transcription factors Anthocyanin1
      (StAN1), basic Helix Loop Helix1 (StbHLH1), and StWD40 were more strongly
      expressed in red and purple potatoes. Expression of 12 other transcription
      factors was not associated with phenylpropanoid content, except for StMYB12B,
      which showed a negative relationship. Increased expression of AN1, bHLH1, and
      WD40 was also associated with environmentally mediated increases in tuber
      phenylpropanoids. Treatment of potato plantlets with sucrose induced
      hydroxycinnamic acids, flavonols, anthocyanins, structural genes, AN1, bHLH1,
      WD40, and genes encoding the sucrose-hydrolysing enzymes SUSY1, SUSY4, and INV2.
      Transient expression of StAN1 in tobacco leaves induced bHLH1, structural genes,
      SUSY1, SUSY4, and INV1, and increased phenylpropanoid amounts. StAN1 infiltration
      into tobacco leaves decreased sucrose and glucose concentrations. In silico
      promoter analysis revealed the presence of MYB and bHLH regulatory elements on
      sucrolytic gene promoters and sucrose-responsive elements on the AN1 promoter.
      These findings reveal an interesting dynamic between AN1, sucrose, and sucrose
      metabolic genes in modulating potato phenylpropanoids. 

PMID- 24098051
TI  - Novel regulatory action of ribosomal inactivation on epithelial Nod2-linked
      proinflammatory signals in two convergent ATF3-associated pathways.
AB  - In response to excessive nucleotide-binding oligomerization domain-containing
      protein 2 (Nod2) stimulation caused by mucosal bacterial components, gut
      epithelia need to activate regulatory machinery to maintain epithelial
      homeostasis. Activating transcription factor 3 (ATF3) is a representative
      regulator in the negative feedback loop that modulates TLR-associated
      inflammatory responses. In the current study, the regulatory effects of ribosomal
      stress-induced ATF3 on Nod2-stimulated proinflammatory signals were assessed.
      Ribosomal inactivation caused persistent ATF3 expression that in turn suppressed
      proinflammatory chemokine production facilitated by Nod2. Decreased chemokine
      production was due to attenuation of Nod2-activated NF-kappaB and early growth
      response protein 1 (EGR-1) signals by ATF3. However, the underlying molecular
      mechanisms involve two convergent regulatory pathways. Although ATF3 induced by
      ribosomal inactivation regulated Nod2-induced EGR-1 expression epigenetically
      through the recruitment of histone deacetylase 1, NF-kappaB regulation was
      associated with posttranscriptional regulation by ATF3 rather than epigenetic
      modification. ATF3 induced by ribosomal inactivation led to the destabilization
      of p65 mRNA caused by nuclear entrapment of transcript-stabilizing human Ag R
      protein via direct interaction with ATF3. These findings demonstrate that
      ribosomal stress-induced ATF3 is a critical regulator in the convergent pathways
      between EGR-1 and NF-kappaB, which contributes to the suppression of Nod2
      activated proinflammatory gene expression. 

PMID- 24098050
TI  - The Arabidopsis adaptor protein AP-3MU interacts with the G-protein beta subunit
      AGB1 and is involved in abscisic acid regulation of germination and post
      germination development.
AB  - Heterotrimeric G-proteins (G-proteins) have been implicated in ubiquitous
      signalling mechanisms in eukaryotes. In plants, G-proteins modulate hormonal and
      stress responses and regulate diverse developmental processes. However, the
      molecular mechanisms of their functions are largely unknown. A yeast two-hybrid
      screen was performed to identify interacting partners of the Arabidopsis G
      protein beta subunit AGB1. One of the identified AGB1-interacting proteins is the
      Arabidopsis adaptor protein AP-3u. The interaction between AGB1 and AP-3u was
      confirmed by an in vitro pull-down assay and bimolecular fluorescence
      complementation assay. Two ap-3u T-DNA insertional mutants were found to be
      hyposensitive to abscisic acid (ABA) during germination and post-germination
      growth, whereas agb1 mutants were hypersensitive to ABA. During seed germination,
      agb1/ap-3u double mutants were more sensitive to ABA than the wild type but less
      sensitive than agb1 mutants. However, in post-germination growth, the double
      mutants were as sensitive to ABA as agb1 mutants. These data suggest that AP-3u
      positively regulates the ABA responses independently of AGB1 in seed germination,
      while AP-3u does require AGB1 to regulate ABA responses during post-germination
      growth. 

PMID- 24098052
TI  - Education of murine NK cells requires both cis and trans recognition of MHC class
      I molecules.
AB  - Although NK cells use invariant receptors to identify diseased cells, they
      nevertheless adapt to their environment, including the presence of certain MHC
      class I (MHC-I) molecules. This NK cell education, which is mediated by
      inhibitory receptors specific for MHC-I molecules, changes the responsiveness of
      activating NK cell receptors (licensing) and modifies the repertoire of MHC-I
      receptors used by NK cells. The fact that certain MHC-I receptors have the
      unusual capacity to recognize MHC-I molecules expressed by other cells (trans)
      and by the NK cell itself (cis) has raised the question regarding possible
      contributions of the two types of interactions to NK cell education. Although the
      analysis of an MHC-I receptor variant suggested a role for cis interaction for NK
      cell licensing, adoptive NK cell transfer experiments supported a key role for
      trans recognition. To reconcile some of these findings, we have analyzed the
      impact of cell type-specific deletion of an MHC-I molecule and of a novel MHC-I
      receptor variant on the education of murine NK cells when these mature under
      steady-state conditions in vivo. We find that MHC-I expression by NK cells (cis)
      and by T cells (trans), and MHC-I recognition in cis and in trans, are both
      needed for NK cell licensing. Unexpectedly, modifications of the MHC-I receptor
      repertoire are chiefly dependent on cis binding, which provides additional
      support for an essential role for this unconventional type of interaction for NK
      cell education. These data suggest that two separate functions of MHC-I receptors
      are needed to adapt NK cells to self-MHC-I. 

PMID- 24098053
TI  - Reduced effectiveness of CD4+Foxp3+ regulatory T cells in CD28-deficient NOD.H
      2h4 mice leads to increased severity of spontaneous autoimmune thyroiditis.
AB  - NOD.H-2h4 mice given NaI in their drinking water develop iodine-accelerated
      spontaneous autoimmune thyroiditis (ISAT) with chronic inflammation of the
      thyroid by T and B cells and production of anti-mouse thyroglobulin (MTg)
      autoantibody. CD28(-/-) NOD.H-2h4 mice, which have reduced numbers of
      CD4(+)Foxp3(+) regulatory T cells (Tregs), were developed to examine the role of
      Tregs in ISAT development. CD28(-/-) NOD.H2-h4 mice develop more severe ISAT than
      do wild-type (WT) mice, with collagen deposition (fibrosis) and low serum T4.
      CD28(-/-) mice have increased expression of proinflammatory cytokines IFN-gamma
      and IL-6, consistent with increased mononuclear cell infiltration and tissue
      destruction in thyroids. Importantly, transferring purified CD4(+)Foxp3(+) Tregs
      from WT mice reduces ISAT severity in CD28(-/-) mice without increasing the total
      number of Tregs, suggesting that endogenous Tregs in CD28(-/-) mice are
      functionally ineffective. Endogenous CD28(-/-) Tregs have reduced surface
      expression of CD27, TNFR2 p75, and glucocorticoid-induced TNFR-related protein
      compared with transferred CD28(+/+) Tregs. Although anti-MTg autoantibody levels
      generally correlate with ISAT severity scores in WT mice, CD28(-/-) mice have
      lower anti-MTg autoantibody responses than do WT mice. The percentages of
      follicular B cells are decreased and those of marginal zone B cells are increased
      in spleens of CD28(-/-) mice, and they have fewer thyroid-infiltrating B cells
      than do WT mice. This suggests that CD28 deficiency has direct and indirect
      effects on the B cell compartment. B cell-deficient (B(-/-)) NOD.H-2h4 mice are
      resistant to ISAT, but CD28(-/-)B(-/-) mice develop ISAT comparable to WT mice
      and have reduced numbers of Tregs compared with WT B(-/-) mice. 

PMID- 24098054
TI  - Selective activation of antigen-experienced T cells by anti-CD3 constrained on
      nanoparticles.
AB  - Activation of T cells through the TCR is mediated by the TCR-CD3 signaling
      complex. Cross linking of this complex with Abs directed against CD3 leads to
      potent activation of T cells. However, such activation is not Ag-specific. We
      exploited the observation that the TCR-CD3 complex is clustered on T cells that
      have been activated by Ag by using anti-CD3 nanoparticles to selectively activate
      Ag-experienced mouse T cells. We find that constraining anti-CD3 on the surface
      of a nanoparticle markedly and selectively enhances proliferation and cytokine
      production of Ag-experienced T cells but does not activate naive T cells. This
      effect was recapitulated in heterogeneous cultures containing mixtures of Ag
      specific CD4(+) or CD8(+) T cells and bystander T cells. Furthermore, in vivo
      anti-CD3-coated nanoparticles increased the expansion of Ag-specific T cells
      following vaccination. Overall, these findings indicate that anti-CD3-coated
      nanoparticles could be use to enhance the efficacy of vaccines and immunotherapy.
      The results also suggest constraining a ligand on the surface of a nanoparticle
      might as general strategy for selectively targeting clustered receptors. 

PMID- 24098056
TI  - Climate Change Denial Books and Conservative Think Tanks: Exploring the
      Connection.
AB  - The conservative movement and especially its think tanks play a critical role in
      denying the reality and significance of anthropogenic global warming (AGW),
      especially by manufacturing uncertainty over climate science. Books denying AGW
      are a crucial means of attacking climate science and scientists, and we examine
      the links between conservative think tanks (CTTs) and 108 climate change denial
      books published through 2010. We find a strong link, albeit noticeably weaker for
      the growing number of self-published denial books. We also examine the national
      origins of the books and the academic backgrounds of their authors or editors,
      finding that with the help of American CTTs climate change denial has spread to
      several other nations and that an increasing portion of denial books are produced
      by individuals with no scientific training. It appears that at least 90% of
      denial books do not undergo peer review, allowing authors or editors to recycle
      scientifically unfounded claims that are then amplified by the conservative
      movement, media, and political elites.

PMID- 24098055
TI  - TGF-beta: guardian of T cell function.
AB  - A fundamental aspect of the adaptive immune system is the generation and
      maintenance of a diverse and self-tolerant T cell repertoire. Through its
      regulation of T cell development, homeostasis, tolerance, and differentiation,
      the highly evolutionarily conserved cytokine TGF-beta critically supports a
      functional T cell pool. The pleiotropic nature of this regulation is likely due
      to the elaborate control of TGF-beta production and activation in the immune
      system, and the intricacy of TGF-beta signaling pathways. In this review we
      discuss the current understanding of TGF-beta regulation of T cells. 

PMID- 24098057
TI  - Characterization and Benzo[a]pyrene Content Analysis of Camellia Seed Oil
      Extracted by a Novel Subcritical Fluid Extraction.
AB  - A novel continuous subcritical n-butane extraction technique for Camellia seed
      oil was explored. The fatty acid composition, physicochemical properties, and
      benzo[a]pyrene content of Camellia seed oil extracted using this subcritical
      technique were analyzed. Orthogonal experiment design (L9(34)) was adopted to
      optimize extraction conditions. At a temperature of 45  degrees C, a pressure of
      0.5 MPa, a time of 50 min and a bulk density of 0.7 kg/L, an extraction yield of
      99.12 +/- 0.20 % was obtained. The major components of Camellia seed oil are
      oleic acid (73.12 +/- 0.40 %), palmitic acid (10.38 +/- 0.05 %), and linoleic
      acid (9.15 +/- 0.03 %). Unsaturated fatty acids represent 83.78 +/- 0.03 % of the
      total fatty acids present. Eight physicochemical indexes were assayed, namely,
      iodine value (83.00 +/- 0.21 g I/100 g), saponification value (154.81 +/- 2.00 mg
      KOH/g), freezing-point (-8.00 +/- 0.10  degrees C), unsaponifiable matter (5.00
      +/- 0.40 g/kg), smoke point (215.00 +/- 1.00  degrees C), acid value (1.24 +/-
      0.03 mg KOH/g), refrigeration test (transparent, at 0  degrees C for 5.5 h), and
      refractive index (1.46 +/- 0.06, at 25  degrees C). Benzo[a]pyrene was not
      detected in Camellia seed oil extracted by continuous subcritical n-butane
      extraction. In comparison, the benzo[a]pyrene levels of crude Camellia seed oil
      extracted by hot press extraction and refined Camellia seed oil were measured at
      26.55 +/- 0.70 and 5.69 +/- 0.04 MUg/kg respectively.

PMID- 24098059
TI  - Controlling the femtosecond laser-driven transformation of dicyclopentadiene into
      cyclopentadiene.
AB  - Dynamics of the chemical transformation of dicyclopentadiene into cyclopentadiene
      in a supersonic molecular beam is elucidated using femtosecond time-resolved
      degenerate pump-probe mass spectrometry. Control of this ultrafast chemical
      reaction is achieved by using linearly chirped frequency modulated pulses. We
      show that negatively chirped femtosecond laser pulses enhance the cyclopentadiene
      photo-product yield by an order of magnitude as compared to that of the
      unmodulated or the positively chirped pulses. This demonstrates that the phase
      structure of femtosecond laser pulse plays an important role in determining the
      outcome of a chemical reaction.

PMID- 24098058
TI  - Genotypic differences in behavioural entropy: unpredictable genotypes are
      composed of unpredictable individuals.
AB  - Intra-genotypic variability (IGV) occurs when individuals with the same genotype,
      raised in the same environment and then tested under the same conditions, express
      different trait values. Game theoretical and bet-hedging models have suggested
      two ways that a single genotype might generate variable behaviour when
      behavioural variation is discrete rather than continuous: behavioural polyphenism
      (a genotype produces different types of individuals, each of which consistently
      expresses a different type of behaviour) or stochastic variability (a genotype
      produces one type of individual who randomly expresses different types of
      behaviour over time). We first demonstrated significant differences across 14
      natural genotypes of male Drosophila melanogaster in the variability (as measured
      by entropy) of their microhabitat choice, in an experiment in which each fly was
      allowed free access to four different types of habitat. We then tested four
      hypotheses about ways that within-individual variability might contribute to
      differences across genotypes in the variability of microhabitat choice. There was
      no empirical support for three hypotheses (behavioural polymorphism, consistent
      choice, or time-based choice), nor could our results be attributed to genotypic
      differences in activity levels. The stochastic variability hypothesis accurately
      predicted the slope and the intercept of the relationship across genotypes
      between entropy at the individual level and entropy at the genotype level.
      However, our initial version of the stochastic model slightly but significantly
      overestimated the values of individual entropy for each genotype, pointing to
      specific assumptions of this model that might need to be adjusted in future
      studies of the IGV of microhabitat choice. This is among a handful of recent
      studies to document genotypic differences in behavioural IGV, and the first to
      explore ways that genotypic differences in within-individual variability might
      contribute to differences among genotypes in the predictability of their
      behaviour.

PMID- 24098060
TI  - Anti-proliferative withanolides from the Solanaceae: a structure-activity study.
AB  - As part of our search for bioactive compounds from plant biodiversity, 29
      withanolides (1, 3-6, 9, 12-18, and 20-35) were recently isolated from three
      members of the Solanaceae: Physalis longifolia, Vassobia breviflora, and Withania
      somnifera. Six derivatives (2, 7, 8, 10, 11, and 19) were prepared from these
      naturally occurring withanolides. All compounds (1-35) were evaluated for in
      vitro anti-proliferative activity against an array of cell lines [melanoma cell
      lines (B16F10, SKMEL28); human head and neck squamous cell carcinomas (HNSCC)
      cell lines (JMAR, MDA1986, DR081-1); breast cancer cell line (Hs578T), and non
      malignant human cell line (MRC5)]. This led to the discovery of 15 withanolides,
      with IC50 values in the range of 0.067-17.4 uM, including withaferin A 1,
      withaferin A 4,27-diacetate 2, 27-O-glucopyranosylwithaferin A 3, withalongolide
      H 4, withalongolide C 5, withalongolide A 6, withalongolide A 4,27-diacetate 7,
      withalongolide A 4,19,27-triacetate 8, withalongolide B 9, withalongolide B 4
      acetate 10, withalongolide B 4,19-diacetate 11, withalongolide D 16,
      withalongolide E 17, withalongolide G 21, and 2,3-dihydrowithaferin A 3-O-sulfate
      22). In order to update the growing literature on withanolides and their
      activities, we summarized the distribution, structural types and anti
      proliferative activities for all published withanolides to date. The structure
      activity relationship analysis (SARA) confirmed the importance of the presence of
      a Delta2-1-oxo- functionality in ring A, a 5beta,6beta-epoxy or 5alpha-chloro
      6beta-hydroxy groupings in ring B, and nine carbon side chain with a lactone
      moiety for cytotoxic activity. Conversely, the SARA indicated that the -OH or -OR
      groups at C-4, 7, 11, 12, 14, 15, 16, 17, 18, 19, 20, 23, 24, 27, 28 were not
      contributors to the observed anti-proliferative activity within the systems
      analyzed.

PMID- 24098061
TI  - Simultaneous grouping pursuit and feature selection over an undirected graph.
AB  - In high-dimensional regression, grouping pursuit and feature selection have their
      own merits while complementing each other in battling the curse of
      dimensionality. To seek a parsimonious model, we perform simultaneous grouping
      pursuit and feature selection over an arbitrary undirected graph with each node
      corresponding to one predictor. When the corresponding nodes are reachable from
      each other over the graph, regression coefficients can be grouped, whose absolute
      values are the same or close. This is motivated from gene network analysis, where
      genes tend to work in groups according to their biological functionalities.
      Through a nonconvex penalty, we develop a computational strategy and analyze the
      proposed method. Theoretical analysis indicates that the proposed method
      reconstructs the oracle estimator, that is, the unbiased least squares estimator
      given the true grouping, leading to consistent reconstruction of grouping
      structures and informative features, as well as to optimal parameter estimation.
      Simulation studies suggest that the method combines the benefit of grouping
      pursuit with that of feature selection, and compares favorably against its
      competitors in selection accuracy and predictive performance. An application to
      eQTL data is used to illustrate the methodology, where a network is incorporated
      into analysis through an undirected graph.

PMID- 24098062
TI  - Whose Rights Count? Negotiating Practice, Policy, and Legal Dilemmas Regarding
      Infant-Parent Contact When Infants are in Out-of-Home Care.
AB  - This article takes a human rights perspective with a view to articulating the
      infant's perspective when the infant has been subjected to abuse, neglect, or
      both and is reliant on the state to ensure his or her health and well-being. When
      a young child is removed from parental care, important and often difficult
      decisions have to be made about subsequent contact between child and parent. We
      consider a number of dilemmas which may arise for practitioners when they are
      assisting child welfare decision makers in relation to contact, and acknowledge
      the limited empirical follow-up studies of the impact of child welfare practice
      and legal decisions on infant outcomes. We draw on the significant and
      substantive evidence base about infant emotional and cognitive development and
      infant-parent attachment relationships as well as infant mental health to
      illuminate the infant's subjective experience in these practice dilemmas. We
      describe innovations in practice from various countries, which seek to shed light
      on the challenges often associated with contact.

PMID- 24098063
TI  - Aging and Sexual Orientation: A 25-Year Review of the Literature.
AB  - In a review of 58 articles published between 1984 and 2008, this article
      synthesizes the recent state of social research on older lesbian, gay male, and
      bisexual adults in order to summarize existing knowledge about these groups, to
      guide future research on aging, and to identify the substantive issues affecting
      their lives. Based on a life-course perspective, the primary research domains
      identified include the interplay of lives and historical times and linked and
      interdependent lives. After reviewing the literature in each of these areas, the
      article presents an examination of the strengths and limitations of the body of
      knowledge and an outline of a blueprint for future research.

PMID- 24098064
TI  - Methodological Considerations in the Analysis of Fecal Glucocorticoid Metabolites
      in Tufted Capuchins (Cebus apella).
AB  - Analysis of fecal glucocorticoid (GC) metabolites has recently become the
      standard method to monitor adrenocortical activity in primates noninvasively.
      However, given variation in the production, metabolism, and excretion of GCs
      across species and even between sexes, there are no standard methods that are
      universally applicable. In particular, it is important to validate assays
      intended to measure GC production, test extraction and storage procedures, and
      consider the time course of GC metabolite excretion relative to the production
      and circulation of the native hormones. This study examines these four
      methodological aspects of fecal GC metabolite analysis in tufted capuchins (Cebus
      apella). Specifically, we conducted an adrenocorticotrophic hormone (ACTH)
      challenge on one male and one female capuchin to test the validity of four GC
      enzyme immunoassays (EIAs) and document the time course characterizing GC
      metabolite excretion in this species. In addition, we compare a common field
      friendly technique for extracting fecal GC metabolites to an established
      laboratory extraction methodology and test for effects of storing "field
      extracts" for up to 1 yr. Results suggest that a corticosterone EIA is most
      sensitive to changes in GC production, provides reliable measures when extracted
      according to the field method, and measures GC metabolites which remain highly
      stable after even 12 mo of storage. Further, the time course of GC metabolite
      excretion is shorter than that described yet for any primate taxa. These results
      provide guidelines for studies of GCs in tufted capuchins, and underscore the
      importance of validating methods for fecal hormone analysis for each species of
      interest.

PMID- 24098065
TI  - Discordance Between Spatial Distributions of Y-Chromosomal and Mitochondrial
      Haplotypes in African Green Monkeys ( Chlorocebus spp.): A Result of
      Introgressive Hybridization or Cryptic Diversity?
AB  - Introgressive hybridization may cause substantial discordances among phylogenies
      based on different genetic markers. Such discordances have been found in diverse
      mammal species including primates. A recent study of mitochondrial DNA (mtDNA)
      revealed several poly- and paraphyletic relationships in African green monkeys
      (Chlorocebus), suggesting contemporary and/or ancient introgressive hybridization
      among almost all parapatric species of the genus. However, mtDNA analyses alone
      do not allow us to draw conclusions concerning introgression events. In this
      study we analyzed two Y chromosomal (Y-chr) markers for 30 African green monkey
      samples and compared the resulting genetic relationships to those based on
      published mtDNA data. In line with the results for mtDNA, we found no Y-chr
      evidence of hypothesized hybridization among Chlorocebus sabaeus and C. tantalus
      in the northern part of the contact zone in West Africa, and we found two
      distinct and distantly related Y-chr haplotypes within the range of C. tantalus,
      suggesting possible cryptic genetic diversity rather than ancient introgressive
      hybridization in this species. In contrast, Y-chr data revealed monophyletic
      relationships within Chlorocebus pygerythrus from East Africa, suggesting that
      mtDNA paraphylies found in this species are most likely to be the result of
      ancient introgressive hybridization and subsequent cytonuclear extinction of an
      earlier taxon. Our results accentuate the importance of analyzing sex chromosomal
      data in addition to mtDNA to obtain more information on the potential outcomes of
      hybridization with respect to genetic and species diversity. Analysis of more
      diverse nuclear marker sets is needed to obtain a more complete picture of the
      African green monkey evolution.

PMID- 24098066
TI  - Bioaerosols of subterraneotherapy chambers at salt mine health resort.
AB  - Nowadays, an inhalation of naturally generated aerosols has again become a widely
      practiced method of balneological treatment of various respiratory diseases. The
      aim of this study was to characterize the microbial aerosol of subterraneotherapy
      chambers at the Bochnia Salt Mine Health Resort in southern Poland. The
      measurements were carried out using a 6-stage Andersen impactor over a period of
      1 year in both indoor (i.e., two subterranean chambers, where curative treatments
      took place) and outdoor air. The maximum bacterial aerosol concentrations in the
      chambers reached 11,688 cfu/m3. In such interiors, a high-performance method of
      microbial contaminant reduction need be introduced, especially when large groups
      of young patients are medically cured. Respecting fungal aerosol, its average
      indoor concentration (88 cfu/m3) was significantly lower than outdoor level (538
      cfu/m3). It confirms that ventilation system provides efficient barrier against
      this type of biologically active propagules. Among identified micro-organisms,
      the most prevalent indoors were Gram-positive cocci, which constituted up to 80 %
      of airborne microflora. As highly adapted to the diverse environments of its
      human host (skin, respiratory tract), they can be easily released in high
      quantities into the air. The number of people introduced into such subterranean
      chambers should be in some way limited. The analysis of microclimate parameters
      revealed that temperature and relative humidity influenced significantly the
      level of bacterial aerosol only. Hence, a constant control of these parameters
      should be scrupulously superintended at this type of subterranean premises.

PMID- 24098067
TI  - The patterns of Corylus and Alnus pollen seasons and pollination periods in two
      Polish cities located in different climatic regions.
AB  - This study compares phenological observations of Corylus (hazel) and Alnus
      (alder) flowering with airborne pollen counts of these taxa recorded using
      volumetric spore traps (2009-2011). The work was carried out in the Polish cities
      of Szczecin and Rzeszow that are located in different climatic regions.
      Correlations between pollen concentrations and meteorological data were
      investigated using Spearman's rank correlation analysis. The timings of hazel and
      alder pollination and the occurrence of airborne pollen varied greatly and were
      significantly influenced by meteorological conditions (p < 0.05). The flowering
      synchronization of hazel and alder pollination in Szczecin and Rzeszow varied
      over the study period. Hazel and alder trees flowered notably earlier in stands
      located in places that were exposed to sunlight (insolated) and sheltered from
      the wind. On the other hand, a delay in the timing of pollination was observed in
      quite sunny but very windy sites. In Rzeszow, maximum hazel pollen concentrations
      did not coincide with the period of full pollination (defined as between 25 %
      hazel and alder and 75 % of flowers open). Conversely, in Szczecin, the highest
      hazel pollen concentrations were recorded during phenophases of the full
      pollination period. The period when the highest alder pollen concentrations were
      recorded varied between sites, with Rzeszow recording the highest concentrations
      at the beginning of pollination and Szczecin recording alder pollen throughout
      the full pollination period. Substantial amounts of hazel and alder pollen grains
      were recorded in the air of Rzeszow (but not Szczecin) before the onset of the
      respective pollen seasons.

PMID- 24098068
TI  - Exploring control parameters of two photon processes in solutions.
AB  - Two-photon microscopy depends extensively on the two-photon absorption cross
      sections of biologically relevant chromophores. High repetition rate (HRR) lasers
      are essential in multiphoton microscopy for generating satisfactory signal to
      noise at low average powers. However, HRR lasers generate thermal distortions in
      samples even with the slightest single photon absorption. We use an optical
      chopper with HRR lasers to intermittently 'blank' irradiation and effectively
      minimize thermal effects to result in a femtosecond z-scan setup that precisely
      measures the two-photon absorption (TPA) cross-sections of chromophores. Though
      several experimental factors impact such TPA measurements, a systematic effort to
      modulate and influence TPA characteristics is yet to evolve. Here, we present the
      effect of several control parameters on the TPA process that are independent of
      chromophore characteristics for femtosecond laser pulse based measurements; and
      demonstrate how the femtosecond laser pulse repetition rate, chromophore
      environment and incident laser polarization can become effective control
      parameters for such nonlinear optical properties.

PMID- 24098069
TI  - A quantitative structure-activity relationship study of anti-HIV activity of
      substituted HEPT using nonlinear models.
AB  - We performed studies on extended series of 79 HEPT ligands (1-[(2
      hydroxyethoxy)methyl]-6-(phenylthio)thymine), inhibitors of HIV reverse
      transcriptase with anti-HIV biological activity, using quantitative structure
      activity relationship (QSAR) methods that imply analysis of correlations and
      representation of models. A suitable set of molecular descriptors was calculated,
      and the genetic algorithm was employed to select those descriptors which resulted
      in the best-fit models. The kernel partial least square and Levenberg-Marquardt
      artificial neural network were utilized to construct the nonlinear QSAR models.
      The proposed methods will be of great significance in this research, and would be
      expected to apply to other similar research fields.

PMID- 24098070
TI  - Health Behavior Theories and Research: Implications for Suicidal Individuals'
      Treatment Linkage and Adherence.
AB  - Treatment linkage and adherence to psychotherapeutic interventions can be
      challenging with suicidal individuals. Health behavior theories, specifically the
      Health Belief Model, Stages of Change, and Theory of Planned Behavior, focus on
      individuals' beliefs, their readiness to change, their perceptions of illness
      severity and "threat," their perceptions of significant others' attitudes toward
      illness and treatment, and their behavioral intentions to change. These
      constructs have relevance both for understanding suicidal individuals' behaviors
      related to treatment utilization and for understanding cultural variations in
      these behaviors. Furthermore, these theories have implications for clinical
      practices aimed at facilitating improved treatment follow-through and adherence.
      After describing the theories and their constructs, clinical examples are
      provided to illustrate applications to practice with suicidal individuals.

PMID- 24098071
TI  - Quality indicators for colorectal cancer screening for colonoscopy.
AB  - The growing importance of colonoscopy in the prevention of colorectal cancer has
      stimulated an effort to identify and track quality indicators for this procedure.
      Several factors have been identified so far which are readily measurable and in
      many cases have been associated with improved patient outcomes. There is also
      ample evidence of variations in performance of this procedure. As a result,
      gathering data about quality indicators may play a vital role in the process of
      continuous quality improvement. Quality indicators for colonoscopy in colorectal
      cancer prevention are described along with the evidence that supports their use
      in benchmarking, quality reporting, and continuous quality improvement.

PMID- 24098072
TI  - Effects of krill oil containing n-3 polyunsaturated fatty acids in phospholipid
      form on human brain function: a randomized controlled trial in healthy elderly
      volunteers.
AB  - BACKGROUND: Krill oil, rich in n-3 (omega-3) polyunsaturated fatty acids (PUFAs)
      incorporated in phosphatidylcholine, has been reported to have many effects on
      physiological function. However, there are few studies using psychophysiological
      methods published that describe the effects of krill oil on brain function. We
      investigated the influence of ingestion of krill oil on cognitive function in
      elderly subjects by using near-infrared spectroscopy and electroencephalography.
      METHODS: A randomized, double-blind, parallel-group comparative study design was
      adopted. Forty-five healthy elderly males aged 61-72 years were assigned to
      receive 12 weeks of treatment with: medium-chain triglycerides as placebo; krill
      oil, which is rich in n-3 PUFAs incorporated in phosphatidylcholine; or sardine
      oil, which is abundant in n-3 PUFAs incorporated in triglycerides. Changes in
      oxyhemoglobin concentrations in the cerebral cortex during memory and calculation
      tasks were measured. The P300 component of event-related potentials was also
      measured during a working memory task. RESULTS: During the working memory task,
      changes in oxyhemoglobin concentrations in the krill oil and sardine oil groups
      were significantly greater than those in the medium-chain triglyceride group at
      week 12. The differential value for P300 latency in the krill oil group was
      significantly lower than that in the medium-chain triglyceride group at week 12.
      With regard to the calculation task, changes in oxyhemoglobin concentrations in
      the krill oil group were significantly greater than those in the medium-chain
      triglyceride group at week 12. CONCLUSION: This study provides evidence that n-3
      PUFAs activate cognitive function in the elderly. This is especially the case
      with krill oil, in which the majority of n-3 PUFAs are incorporated into
      phosphatidylcholine, causing it to be more effective than sardine oil, in which n
      3 PUFAs are present as triglycerides.

PMID- 24098074
TI  - Carotid intima-media thickness and plaque occurrence in predicting stable
      angiographic coronary artery disease.
AB  - BACKGROUND: Carotid intima-media thickness (CIMT) and plaque formation have been
      used as surrogate end-points for evaluating the regression and/or progression of
      atherosclerotic cardiovascular disease, but their predictive value for stable
      coronary artery disease (CAD) is inconclusive. METHODS: Carotid ultrasonography
      was performed in patients who underwent noninvasive multislice computed
      tomography (MSCT) angiography for CAD suspected, due to chest pain. CIMT and
      plaque formation on the left and right common carotid arteries (CCAs), carotid
      bulb (CB), and proximal internal carotid arteries (ICAs) were evaluated, and the
      relationship between angiographic CAD, CIMT, and plaque formation was determined.
      RESULTS: 120 patients (95 male; 25 female), with a mean age +/- standard
      deviation of 61 +/- 11 years (range: 35-89 years) were recruited. Because age had
      a significant impact on CAD (r = 0.191; P = 0.036), CCA plaques (r = 0.368; P =
      0.001), ICA plaques (r = 0.334; P = 0.004), and mean CIMT (r = 0.436; P = 0.001),
      patients were divided into two groups aged <60 years and >=60 years. In the <60
      years group, CIMT-CB was significantly higher in patients with CAD (P = 0.041),
      while in the >=60 years group, mean CIMT, CIMT-CCA, and CIMT-CB were
      significantly higher in patients with CAD (P < 0.05, for each). In both groups,
      the occurrence of carotid plaques was significantly higher in patients with CAD
      than in those without CAD (P < 0.007, for each). After controlling for other risk
      factors, carotid plaques were an independent predictor of CAD in both groups (P <
      0.05, for each), while CIMT-CB could independently predict CAD only in patients
      >=60 years old (P = 0.031). CONCLUSION: Our findings suggest that carotid plaques
      are a strong predictor of stable CAD. However, CIMT-CB could predict stable CAD
      only in patients over 60 years of age.

PMID- 24098075
TI  - The Nanomaterial Registry: facilitating the sharing and analysis of data in the
      diverse nanomaterial community.
AB  - The amount of data being generated in the nanotechnology research space is
      significant, and the coordination, sharing, and downstream analysis of the data
      is complex and consistently deliberated. The complexities of the data are due in
      large part to the inherently complicated characteristics of nanomaterials. Also,
      testing protocols and assays used for nanomaterials are diverse and lacking
      standardization. The Nanomaterial Registry has been developed to address such
      challenges as the need for standard methods, data formatting, and controlled
      vocabularies for data sharing. The Registry is an authoritative, web-based tool
      whose purpose is to simplify the community's level of effort in assessing
      nanomaterial data from environmental and biological interaction studies. Because
      the Registry is meant to be an authoritative resource, all data-driven content is
      systematically archived and reviewed by subject-matter experts. To support and
      advance nanomaterial research, a set of minimal information about nanomaterials
      (MIAN) has been developed and is foundational to the Registry data model. The
      MIAN has been used to create evaluation and similarity criteria for nanomaterials
      that are curated into the Registry. The Registry is a publicly available resource
      that is being built through collaborations with many stakeholder groups in the
      nanotechnology community, including industry, regulatory, government, and
      academia. Features of the Registry website (http://www.nanomaterialregistry.org)
      currently include search, browse, side-by-side comparison of nanomaterials,
      compliance ratings based on the quality and quantity of data, and the ability to
      search for similar nanomaterials within the Registry. This paper is a
      modification and extension of a proceedings paper for the Institute of Electrical
      and Electronics Engineers. 

PMID- 24098073
TI  - Upregulation of genes related to bone formation by gamma-amino butyric acid and
      gamma-oryzanol in germinated brown rice is via the activation of GABAB-receptors
      and reduction of serum IL-6 in rats.
AB  - BACKGROUND: Osteoporosis and other bone degenerative diseases are among the most
      challenging non-communicable diseases to treat. Previous works relate bone loss
      due to osteoporosis with oxidative stress generated by free radicals and
      inflammatory cytokines. Alternative therapy to hormone replacement has been an
      area of interest to researchers for almost three decades due to hormone therapy
      associated side effects. METHODS: In this study, we investigated the effects of
      gamma-amino butyric acid (GABA), gamma-oryzanol (ORZ), acylated steryl glucosides
      (ASG), and phenolic extracts from germinated brown rice (GBR) on the expression
      of genes related to bone metabolism, such as bone morphogenic protein-2 (BMP-2),
      secreted protein acidic and rich in cysteine (SPARC), runt-related transcription
      factor 2 (RUNX-2), osteoblast-specific transcription factor osterix (Osx),
      periostin, osteoblast specific factor (Postn), collagen 1&2 (Col1&2), calcitonin
      receptor gene (CGRP); body weight measurement and also serum interleukin-6 (IL-6)
      and osteocalcin, in serum and bone. Rats were treated with GBR, ORZ, GABA, and
      ASG at (100 and 200 mg/kg); estrogen (0.2 mg/kg), or remifemin (10 and 20 mg/kg),
      compared to ovariectomized non-treated group as well as non-ovariectomized non
      treated (sham) group. Enzyme-linked immunosorbent assay was used to measure the
      IL-6 and osteocalcin levels at week 2, 4, and 8, while the gene expression in the
      bone tissue was determined using the Genetic Analysis System (Beckman Coulter
      Inc., Brea, CA, USA). RESULTS: The results indicate that groups treated with GABA
      (100 and 200 mg/kg) showed significant upregulation of SPARC, calcitonin
      receptor, and BMP-2 genes (P < 0.05), while the ORZ-treated group (100 and 200
      mg/kg) revealed significant (P < 0.05) upregulation of Osx, Postn, RUNX-2, and
      Col1&2. Similarly, IL-6 concentration decreased, while osteocalcin levels
      increased significantly (P < 0.05) in the treated groups as compared to
      ovariectomized non-treated groups. CONCLUSION: GABA and ORZ from GBR stimulates
      osteoblastogenesis by upregulation of bone formation genes, possibly via the
      activation of GABAB receptors and by inhibiting the activity of inflammatory
      cytokines and reactive oxygen species. Therefore, it could be used effectively in
      the management of osteoporosis.

PMID- 24098076
TI  - NEIMiner: nanomaterial environmental impact data miner.
AB  - As more engineered nanomaterials (eNM) are developed for a wide range of
      applications, it is crucial to minimize any unintended environmental impacts
      resulting from the application of eNM. To realize this vision, industry and
      policymakers must base risk management decisions on sound scientific information
      about the environmental fate of eNM, their availability to receptor organisms
      (eg, uptake), and any resultant biological effects (eg, toxicity). To address
      this critical need, we developed a model-driven, data mining system called
      NEIMiner, to study nanomaterial environmental impact (NEI). NEIMiner consists of
      four components: NEI modeling framework, data integration, data management and
      access, and model building. The NEI modeling framework defines the scope of NEI
      modeling and the strategy of integrating NEI models to form a layered,
      comprehensive predictability. The data integration layer brings together
      heterogeneous data sources related to NEI via automatic web services and web
      scraping technologies. The data management and access layer reuses and extends a
      popular content management system (CMS), Drupal, and consists of modules that
      model the complex data structure for NEI-related bibliography and
      characterization data. The model building layer provides an advanced analysis
      capability for NEI data. Together, these components provide significant value to
      the process of aggregating and analyzing large-scale distributed NEI data. A
      prototype of the NEIMiner system is available at http://neiminer.i-a-i.com/. 

PMID- 24098077
TI  - Predictive modeling of nanomaterial exposure effects in biological systems.
AB  - BACKGROUND: Predictive modeling of the biological effects of nanomaterials is
      critical for industry and policymakers to assess the potential hazards resulting
      from the application of engineered nanomaterials. METHODS: We generated an
      experimental dataset on the toxic effects experienced by embryonic zebrafish due
      to exposure to nanomaterials. Several nanomaterials were studied, such as metal
      nanoparticles, dendrimer, metal oxide, and polymeric materials. The embryonic
      zebrafish metric (EZ Metric) was used as a screening-level measurement
      representative of adverse effects. Using the dataset, we developed a data mining
      approach to model the toxic endpoints and the overall biological impact of
      nanomaterials. Data mining techniques, such as numerical prediction, can assist
      analysts in developing risk assessment models for nanomaterials. RESULTS: We
      found several important attributes that contribute to the 24 hours post
      fertilization (hpf) mortality, such as dosage concentration, shell composition,
      and surface charge. These findings concur with previous studies on nanomaterial
      toxicity using embryonic zebrafish. We conducted case studies on modeling the
      overall effect/impact of nanomaterials and the specific toxic endpoints such as
      mortality, delayed development, and morphological malformations. The results show
      that we can achieve high prediction accuracy for certain biological effects, such
      as 24 hpf mortality, 120 hpf mortality, and 120 hpf heart malformation. The
      results also show that the weighting scheme for individual biological effects has
      a significant influence on modeling the overall impact of nanomaterials. Sample
      prediction models can be found at http://neiminer.i-a-i.com/nei_models.
      CONCLUSION: The EZ Metric-based data mining approach has been shown to have
      predictive power. The results provide valuable insights into the modeling and
      understanding of nanomaterial exposure effects.

PMID- 24098078
TI  - A framework for grouping nanoparticles based on their measurable characteristics.
AB  - BACKGROUND: There is a need to take a broader look at nanotoxicological studies.
      Eventually, the field will demand that some generalizations be made. To begin to
      address this issue, we posed a question: are metal colloids on the nanometer-size
      scale a homogeneous group? In general, most people can agree that the
      physicochemical properties of nanomaterials can be linked and related to their
      induced toxicological responses. METHODS: The focus of this study was to
      determine how a set of selected physicochemical properties of five specific metal
      based colloidal materials on the nanometer-size scale - silver, copper, nickel,
      iron, and zinc - could be used as nanodescriptors that facilitate the grouping of
      these metal-based colloids. RESULTS: The example of the framework pipeline
      processing provided in this paper shows the utility of specific statistical and
      pattern recognition techniques in grouping nanoparticles based on experimental
      data about their physicochemical properties. Interestingly, the results of the
      analyses suggest that a seemingly homogeneous group of nanoparticles could be
      separated into sub-groups depending on interdependencies observed in their
      nanodescriptors. CONCLUSION: These particles represent an important category of
      nanomaterials that are currently mass produced. Each has been reputed to induce
      toxicological and/or cytotoxicological effects. Here, we propose an experimental
      methodology coupled with mathematical and statistical modeling that can serve as
      a prototype for a rigorous framework that aids in the ability to group
      nanomaterials together and to facilitate the subsequent analysis of trends in
      data based on quantitative modeling of nanoparticle-specific structure-activity
      relationships. The computational part of the proposed framework is rather general
      and can be applied to other groups of nanomaterials as well.

PMID- 24098079
TI  - Feature selection and survival modeling in The Cancer Genome Atlas.
AB  - PURPOSE: Personalized medicine is predicated on the concept of identifying
      subgroups of a common disease for better treatment. Identifying biomarkers that
      predict disease subtypes has been a major focus of biomedical science. In the era
      of genome-wide profiling, there is controversy as to the optimal number of genes
      as an input of a feature selection algorithm for survival modeling. PATIENTS AND
      METHODS: The expression profiles and outcomes of 544 patients were retrieved from
      The Cancer Genome Atlas. We compared four different survival prediction methods:
      (1) 1-nearest neighbor (1-NN) survival prediction method; (2) random patient
      selection method and a Cox-based regression method with nested cross-validation;
      (3) least absolute shrinkage and selection operator (LASSO) optimization using
      whole-genome gene expression profiles; or (4) gene expression profiles of cancer
      pathway genes. RESULTS: The 1-NN method performed better than the random patient
      selection method in terms of survival predictions, although it does not include a
      feature selection step. The Cox-based regression method with LASSO optimization
      using whole-genome gene expression data demonstrated higher survival prediction
      power than the 1-NN method, but was outperformed by the same method when using
      gene expression profiles of cancer pathway genes alone. CONCLUSION: The 1-NN
      survival prediction method may require more patients for better performance, even
      when omitting censored data. Using preexisting biological knowledge for survival
      prediction is reasonable as a means to understand the biological system of a
      cancer, unless the analysis goal is to identify completely unknown genes relevant
      to cancer biology.

PMID- 24098080
TI  - Rough sets for in silico identification of differentially expressed miRNAs.
AB  - The microRNAs, also known as miRNAs, are the class of small noncoding RNAs. They
      repress the expression of a gene posttranscriptionally. In effect, they regulate
      expression of a gene or protein. It has been observed that they play an important
      role in various cellular processes and thus help in carrying out normal
      functioning of a cell. However, dysregulation of miRNAs is found to be a major
      cause of a disease. Various studies have also shown the role of miRNAs in cancer
      and the utility of miRNAs for the diagnosis of cancer and other diseases. Unlike
      with mRNAs, a modest number of miRNAs might be sufficient to classify human
      cancers. However, the absence of a robust method to identify differentially
      expressed miRNAs makes this an open problem. In this regard, this paper presents
      a novel approach for in silico identification of differentially expressed miRNAs
      from microarray expression data sets. It integrates judiciously the theory of
      rough sets and merit of the so-called B.632+ bootstrap error estimate. While
      rough sets select relevant and significant miRNAs from expression data, the
      B.632+ error rate minimizes the variability and bias of the derived results. The
      effectiveness of the proposed approach, along with a comparison with other
      related approaches, is demonstrated on several miRNA microarray expression data
      sets, using the support vector machine. 

PMID- 24098081
TI  - Using mathematical models to understand the effect of nanoscale roughness on
      protein adsorption for improving medical devices.
AB  - Surface roughness and energy significantly influence protein adsorption on to
      biomaterials, which, in turn, controls select cellular adhesion to determine the
      success and longevity of an implant. To understand these relationships at a
      fundamental level, a model was originally proposed by Khang et al to correlate
      nanoscale surface properties (specifically, nanoscale roughness and energy) to
      protein adsorption, which explained the greater cellular responses on
      nanostructured surfaces commonly reported in the literature today. To test this
      model for different surfaces from what was previously used to develop that model,
      in this study we synthesized highly ordered poly(lactic-co-glycolic acid)
      surfaces of identical chemistry but altered nanoscale surface roughness and
      energy using poly(dimethylsiloxane) molds of polystyrene beads. Fibronectin and
      collagen type IV adsorption studies showed a linear adsorption behavior as the
      surface nanoroughness increased. This supported the general trends observed by
      Khang et al. However, when fitting such data to the mathematical model
      established by Khang et al, a strong correlation did not result. Thus, this study
      demonstrated that the equation proposed by Khang et al to predict protein
      adsorption should be modified to accommodate for additional nanoscale surface
      property contributions (ie, surface charge) to make the model more accurate. In
      summary, results from this study provided an important step in developing future
      mathematical models that can correlate surface properties (such as nanoscale
      roughness and surface energy) to initial protein adsorption events important to
      promote select cellular adhesion. These criteria are critical for the fundamental
      understanding of the now well-documented increased tissue growth on nanoscale
      materials. 

PMID- 24098082
TI  - Estimation of the displacement of cardiac substructures and the motion of the
      coronary arteries using electrocardiographic gating.
AB  - PURPOSE: The aim of this study was to quantify the displacement of cardiac
      substructures, including the anterior myocardial territory (AMT), left ventricle,
      and coronary arteries during a normal cardiac cycle. MATERIALS AND METHODS:
      Computed tomography (CT) images with retrospective electrocardiographic gating of
      17 eligible patients were obtained. All images were reconstructed automatically
      for the end-diastolic and end-systolic phases. CT scanning without contrast at a
      random phase and a selected vertebral body were used as references to measure
      three-dimensionaldisplacements of the cardiac substructures. RESULTS: The
      displacement between the end-diastolic and end-systolic phases (Dd-s) was greater
      than that between the end-systolic and random phases and between the end
      diastolic and random cardiac phases. The largest displacements for the heart were
      in the left, posterior, and inferior directions with an average Dd-s of
      approximately 4-6 mm. The average Dd-s for the AMT and left ventricle was 1.2-2.7
      mm in the anterior and right directions, 4.3-7.8 mm in left and posterior
      directions, and 4.9-6.3 mm in superior and inferior directions. For the coronary
      arteries, the average Dd-s was 2.8-5.9 mm in the anterior-posterior direction,
      3.5-6.6 mm in left-right direction, and 3.8-5.3 mm in the superior-inferior
      direction. Inter-observer agreement was excellent for the heart, AMT, and left
      ventricle (kappa coefficient, >0.75 for all) and good for most coronary arteries
      in three dimensions (kappa coefficient, 0.511-0.687). The Dd-s did not differ
      significantly between men and women. CONCLUSION: Most average displacements of
      the cardiac substructures and coronary arteries were 3-8 mm in three dimensions.
      These findings will be useful to accurately estimate the radiation dose to
      cardiac substructures during thoracic radiation and to evaluate the risk of
      radiation-related heart disease.

PMID- 24098083
TI  - Double siRNA-targeting of cIAP2 and LIVIN results in synergetic sensitization of
      HCT-116 cells to oxaliplatin treatment.
AB  - PURPOSE: Most colon cancers show low sensitivity to treatment with oxaliplatin
      and a specific strategy is needed to overcome this problem. Our approach uses RNA
      interference to silence the expression of target genes responsible for the
      development of oxaliplatin resistance. Profile analysis of genes related to the
      regulation of apoptosis allowed identification of target genes showing the
      greatest degree of upregulation in response to oxaliplatin exposure. METHODS: We
      designed a panel of genes with functions closely related to inactivation of the
      caspase cascade, endoplasmic reticulum stress reduction, and drug metabolism. The
      candidate genes were silenced by means of specific small interfering RNA (siRNA)
      oligonucleotides. RESULTS: The caspase 3 and 9 inhibitors of apoptosis 2 (cIAP2)
      and LIVIN were found to be the most dose-responsive genes during the period of
      oxaliplatin treatment. Two-fold sensitization of cells to oxaliplatin was
      observed with independent knockdown of either cIAP2 or LIVIN expression. siRNA
      silencing of both targets produced a five-fold increase in oxaliplatin
      sensitivity of HCT-116 cells. CONCLUSION: A dose-dependent approach revealed
      reliable targets for siRNA-silencing under low doses of oxaliplatin. Targeting
      the key proapoptotic chain with several specific siRNAs resulted in synergetic
      sensitization of HCT-116 cells to oxaliplatin treatment.

PMID- 24098084
TI  - The relationship between Lin28 and the chemotherapy response of gastric cancer.
AB  - OBJECTIVE: The aim of the study reported here was to identify whether a stem cell
      biomarker, Lin28, may predict the pathologic tumor response to neoadjuvant
      chemotherapy for patients with locally advanced gastric cancer. METHODS: The
      study enrolled 47 patients with gastric cancer who underwent neoadjuvant
      chemotherapy followed by surgery between July 2004 and March 2012. Cancer tissue
      was biopsied by gastroscopy and Lin28 expression in the tissue was measured by
      immunohistochemistry. Statistical analyses were performed to identify the
      relationship between Lin28 expression and tumor regression grade. RESULTS: Of the
      47 cases, pathologic nonresponse was observed in 29 (61.7%) and pathologic
      response in 18 (38.3%). Receiver-operating characteristic curve analysis showed
      that the histoscore of Lin28 expression with 0.325 as a cutoff value could
      differentiate between pathologic response and nonresponse. Multivariable analysis
      showed that Lin28 expression was an independent predictive factor for pathologic
      response to neoadjuvant chemotherapy (P = 0.006). CONCLUSION: Lin28 expression
      was associated with pathologic tumor response in locally advanced gastric cancer
      patients undergoing neoadjuvant chemotherapy. This may suggest that Lin28 can
      serve as a predictive biomarker for neoadjuvant chemotherapy in patients with
      gastric cancer.

PMID- 24098085
TI  - Using observational data to inform the design of a prospective effectiveness
      study for a novel insulin delivery device.
AB  - OBJECTIVE: To inform the design and assess the feasibility of a prospective
      effectiveness study evaluating an insulin delivery device for patients with
      diabetes mellitus to be conducted within the membership of a large US commercial
      insurer. METHODS: Providers who issued >=1 insulin prescription between January
      1, 2011 and September 30, 2011 were selected from administrative claims contained
      in the HealthCore Integrated Research Database(SM). Adult diabetes patients with
      visits to these providers were identified. Providers were dichotomized into high-
      (HVPs) and low-volume providers (LVPs) based on median number of diabetes
      patients per provider. RESULTS: We identified 15,349 HVPs and 15,313 LVPs (median
      number of patients = 14). Most HVPs were located in the Midwest (6,291 [41.0%])
      and South (5,092 [33.2%]), while LVPs were evenly distributed across regions.
      Over 80% (12,769) of HVPs practiced family or internal medicine; 6.4% (989) were
      endocrinologists. HVPs prescribed insulin to an average of 25% of patients.
      Patients of HVPs (522,527) had similar characteristics as patients of LVPs
      (80,669), except for geographical dispersion, which followed that of providers.
      Approximately 65% of patients were aged 21-64 years and 97% had type 2 diabetes.
      Among patients with >=1 available HbA1C result during 2011 (103,992), 48.3%
      (50,193) had an average HbA1C >=7.0%. Among patients initiating insulin, 79.6%
      (22,205) had an average HbA1C >=7.0%. CONCLUSION: The observed provider and
      patient populations support the feasibility of the prospective study. Sampling of
      patients from HVPs is efficient while minimizing bias as patient characteristics
      are similar to those from LVPs. The study also highlights unmet needs for
      improved glycemic control since approximately half of patients with diabetes are
      not on goal.

PMID- 24098086
TI  - Cost of noninfectious comorbidities in patients with HIV.
AB  - OBJECTIVES: We hypothesized that the increased prevalence of noninfectious
      comorbidities (NICMs) observed among HIV-infected patients may result in
      increased direct costs of medical care compared to the general population. Our
      objective was to provide estimates of and describe factors contributing to direct
      costs for medical care among HIV-infected patients, focusing on NICM care
      expenditure. METHODS: A case-control study analyzing direct medical care costs in
      2009. Antiretroviral therapy (ART)-experienced HIV-infected patients (cases) were
      compared to age, sex, and race-matched adults from the general population,
      included in the CINECA ARNO database (controls). NICMs evaluated included
      cardiovascular disease, hypertension, diabetes mellitus, bone fractures, and
      renal failure. Medical care cost information evaluated included pharmacy,
      outpatient, and inpatient hospital expenditures. Linear regression models were
      constructed to evaluate predictors of total care cost for the controls and cases.
      RESULTS: There were 2854 cases and 8562 controls. Mean age was 46 years and 37%
      were women. We analyzed data from 29,275 drug prescription records. Positive
      predictors of health care cost in the overall population: HIV infection (beta =
      2878; confidence interval (CI) = 2001-3755); polypathology (beta = 8911; CI =
      8356-9466); age (beta = 62; CI = 45-79); and ART exposure (beta = 18,773; CI =
      17,873-19,672). Predictors of health care cost among cases: Center for Disease
      Control group C (beta = 1548; CI = 330-2766); polypathology (beta = 11,081; CI =
      9447-12,716); age < 50 years (beta = 1903; CI = 542-3264); protease inhibitor
      exposure (per month of use; beta = 69; CI = 53-85); CD4 count < 200 cells/mm(3)
      (beta = 5438; CI = 3082-7795); and ART drug change (per change; beta = 911; CI =
      716-1106). CONCLUSION: Total cost of medical care is higher in cases than
      controls. Lower medical costs associated with higher CD4 strata are offset by
      increases in the care costs needed for advancing age, particularly for NICMs.

PMID- 24098087
TI  - Onset and duration of effect of incobotulinumtoxinA, onabotulinumtoxinA, and
      abobotulinumtoxinA in the treatment of glabellar frown lines: a randomized,
      double-blind study.
AB  - BACKGROUND: Three botulinum neurotoxin type A preparations (incobotulinumtoxinA,
      onabotulinumtoxinA, and abobotulinumtoxinA) are widely approved in Europe and in
      the US for the treatment of glabellar frown lines. The purpose of this study was
      to determine and compare the time to onset and duration of treatment effect of
      incobotulinumtoxinA, onabotulinumtoxinA, and abobotulinumtoxinA for the treatment
      of glabellar frown lines. SUBJECTS AND METHODS: Subjects aged 20-60 years with
      moderate to severe glabellar frown lines received one treatment of either 21
      units (U) incobotulinumtoxinA, 21 U onabotulinumtoxinA, or 63 U
      abobotulinumtoxinA. Assessments were made over a period of 180 days. Onset of
      treatment effect was defined as the day that the observer noted a decrease in
      glabellar muscle activity compared with baseline photographs and videos. Duration
      of treatment effect was defined as the time until glabellar muscle action
      returned to the baseline level. Analyses were performed using a Weibull log(T)
      regression model. RESULTS: The study enrolled 180 subjects; 60 per group. For all
      three products, onset of treatment effect occurred earlier in female subjects
      compared to male subjects. For both sexes, a significantly earlier time to onset
      of treatment effect was seen for incobotulinumtoxinA compared to
      onabotulinumtoxinA and abobotulinumtoxinA; in female subjects these times were
      3.02 days, 5.29 days, and 5.32 days, respectively. The duration of treatment
      effect was longer for incobotulinumtoxinA compared to onabotulinumtoxinA and
      abobotulinumtoxinA; for all products, treatment effect duration was longer in
      females than in males. Time to onset was not a predictor of treatment duration.
      CONCLUSION: IncobotulinumtoxinA demonstrated a more rapid onset and a longer
      duration of treatment effect than onabotulinumtoxinA (1:1 dose ratio) and
      abobotulinumtoxinA (1:3 dose ratio). Onset of effect was faster and duration of
      effect was longer in female subjects compared to male subjects.

PMID- 24098088
TI  - Erratum: Burden of comorbidities among Japanese patients with atrial
      fibrillation: a case study of dyspepsia [Corrigendum].
AB  - [This corrects the article on p. 51 in vol. 6, PMID: 23717048.].

PMID- 24098089
TI  - A sensitivity analysis of the Children's Treatment Network trial: a randomized
      controlled trial of integrated services versus usual care for children with
      special health care needs.
AB  - BACKGROUND: The value of integrated care through comprehensive, coordinated, and
      family-centered services has been increasingly recognized for improving health
      outcomes of children with special health care needs (CSHCN). In a randomized
      controlled trial (RCT), the integrated care provided through the Children's
      Treatment Network (CTN) was compared with usual care in improving the
      psychosocial health of target CSHCN. In this paper, we aimed to estimate the
      effect of CTN care by conducting multiple analyses to handle noncompliance in the
      trial. METHODS: The trial recruited target children in Simcoe County and York
      Region, ON, Canada. Children were randomized to receive CTN or usual care and
      were followed for 2 years. The CTN group received integrated services through
      multiple providers to address their specific needs while the usual care group
      continued to receive care directed by their parents. The outcome was change in
      psychosocial quality of life at 2 years. We conducted intention-to-treat, as
      treated, per-protocol, and instrumental variable analyses to analyze the outcome.
      RESULTS: The trial randomized 445 children, with 229 in the intervention group
      and 216 in the control group. During follow-up, 52% of children in the
      intervention group did not receive complete CTN care for various reasons. At 2
      years, we did not find a significant improvement in psychosocial quality of life
      among the children receiving CTN care compared with usual care (intention-to
      treat mean difference 1.50, 95% confidence interval -1.49 to 4.50; P = 0.32).
      Other methods of analysis yielded similar results. CONCLUSION: Although the
      effect of CTN care was not significant, there was evidence showing benefits of
      integrated care for CSHCN. More RCTs are needed to demonstrate the magnitude of
      such an effect. The CTN study highlights the key challenges in RCTs when
      assessing interventions involving integrated care, and informs further RCTs
      including similar evaluations.

PMID- 24098090
TI  - The Acoela: on their kind and kinships, especially with nemertodermatids and
      xenoturbellids (Bilateria incertae sedis).
AB  - Acoels are among the simplest worms and therefore have often been pivotal in
      discussions of the origin of the Bilateria. Initially thought primitive because
      of their "planula-like" morphology, including their lumenless digestive system,
      they were subsequently dismissed by many morphologists as a specialized clade of
      the Platyhelminthes. However, since molecular phylogenies placed them outside the
      Platyhelminthes and outside all other phyla at the base of the Bilateria, they
      became the focus of renewed debate and research. We review what is currently
      known of acoels, including information regarding their morphology, development,
      systematics, and phylogenetic relationships, and put some of these topics in a
      historical perspective to show how the application of new methods contributed to
      the progress in understanding these animals. Taking all available data into
      consideration, clear-cut conclusions cannot be made; however, in our view it
      becomes successively clearer that acoelomorphs are a "basal" but "divergent"
      branch of the Bilateria.

PMID- 24098091
TI  - Comparisons of short-term efficacy between individual and group cognitive
      behavioral therapy for primary insomnia.
AB  - The purpose of this study was to compare the efficacy of individual and group
      cognitive behavioral therapy for insomnia (CBT-I) in outpatients with primary
      insomnia diagnosed by DSM-IV-TR. The participants were 20 individually treated (I
      CBT-I) and 25 treated in a group therapy format (three to five patients per
      group) (G-CBT-I), which showed no significant difference regarding demographic
      variables between groups. The same components of CBT-I stimulus control therapy,
      sleep restriction therapy, cognitive therapy, and sleep hygiene education were
      applied on both groups. The short-term outcome (4 weeks after treatment) was
      measured by sleep logs, actigraphy, the Pittsburgh Sleep Quality Index (PSQI),
      and the Dysfunctional Beliefs and Attitudes about Sleep Scale (DBAS), and was
      compared between I-CBT-I and G-CBT-I. The results indicated that CBT-I was
      effective in improving subjective and objective sleep parameters and subjective
      sleep evaluations for both individual and group treatment. However, I-CBT-I
      resulted in significantly better improvements over G-CBT-I, in (i) objective and
      subjective sleep onset latency time, (ii) objective sleep efficacy and moving
      time during sleeping, (iii) overall sleep quality and duration of actual sleep
      time in PSQI, (iv) consequences of insomnia, control and predictability of sleep,
      sleep requirement expectation, and sleep-promoting practices in DBAS. The present
      study suggested the superiority of I-CBT-I over G-CBT-I in clinical settings, and
      further evaluations are necessary.

PMID- 24098092
TI  - ROBUSTNESS OF SIGNALING GRADIENT IN DROSOPHILA WING IMAGINAL DISC.
AB  - Quasi-stable gradients of signaling protein molecules (known as morphogens or
      ligands) bound to cell receptors are known to be responsible for differential
      cell signaling and gene expressions. From these follow different stable cell
      fates and visually patterned tissues in biological development. Recent studies
      have shown that the relevant basic biological processes yield gradients that are
      sensitive to small changes in system characteristics (such as expression level of
      morphogens or receptors) or environmental conditions (such as temperature
      changes). Additional biological activities must play an important role in the
      high level of robustness observed in embryonic patterning for example. It is
      natural to attribute observed robustness to various type of feedback control
      mechanisms. However, our own simulation studies have shown that feedback control
      is neither necessary nor sufficient for robustness of the morphogen
      decapentaplegic (Dpp) gradient in wing imaginal disc of Drosophilas. Furthermore,
      robustness can be achieved by substantial binding of the signaling morphogen Dpp
      with nonsignaling cell surface bound molecules (such as heparan sulfate
      proteoglygans) and degrading the resulting complexes at a sufficiently rapid
      rate. The present work provides a theoretical basis for the results of our
      numerical simulation studies.

PMID- 24098093
TI  - Old Issues in New Jacket: Power and Validation in the Context of Mixture
      Modeling.

PMID- 24098094
TI  - The accuracy of quantum chemical methods for large noncovalent complexes.
AB  - We evaluate the performance of the most widely used wavefunction, density
      functional theory, and semiempirical methods for the description of noncovalent
      interactions in a set of larger, mostly dispersion-stabilized noncovalent
      complexes (the L7 data set). The methods tested include MP2, MP3, SCS-MP2,
      SCS(MI)-MP2, MP2.5, MP2.X, MP2C, DFT-D, DFT-D3 (B3-LYP-D3, B-LYP-D3, TPSS-D3,
      PW6B95-D3, M06-2X-D3) and M06-2X, and semiempirical methods augmented with
      dispersion and hydrogen bonding corrections: SCC-DFTB-D, PM6-D, PM6-DH2 and PM6
      D3H4. The test complexes are the octadecane dimer, the guanine trimer, the
      circumcoronene...adenine dimer, the coronene dimer, the guanine-cytosine dimer,
      the circumcoronene...guanine-cytosine dimer, and an amyloid fragment trimer
      containing phenylalanine residues. The best performing method is MP2.5 with
      relative root mean square deviation (rRMSD) of 4 %. It can thus be recommended as
      an alternative to the CCSD(T)/CBS (alternatively QCISD(T)/CBS) benchmark for
      molecular systems which exceed current computational capacity. The second best
      non-DFT method is MP2C with rRMSD of 8 %. A method with the most favorable
      "accuracy/cost" ratio belongs to the DFT family: BLYP-D3, with an rRMSD of 8 %.
      Semiempirical methods deliver less accurate results (the rRMSD exceeds 25 %).
      Nevertheless, their absolute errors are close to some much more expensive methods
      such as M06-2X, MP2 or SCS(MI)-MP2, and thus their price/performance ratio is
      excellent.

PMID- 24098095
TI  - Thermal adaptation of conformational dynamics in ribonuclease H.
AB  - The relationship between inherent internal conformational processes and enzymatic
      activity or thermodynamic stability of proteins has proven difficult to
      characterize. The study of homologous proteins with differing thermostabilities
      offers an especially useful approach for understanding the functional aspects of
      conformational dynamics. In particular, ribonuclease HI (RNase H), an 18 kD
      globular protein that hydrolyzes the RNA strand of RNA:DNA hybrid substrates, has
      been extensively studied by NMR spectroscopy to characterize the differences in
      dynamics between homologs from the mesophilic organism E. coli and the
      thermophilic organism T. thermophilus. Herein, molecular dynamics simulations are
      reported for five homologous RNase H proteins of varying thermostabilities and
      enzymatic activities from organisms of markedly different preferred growth
      temperatures. For the E. coli and T. thermophilus proteins, strong agreement is
      obtained between simulated and experimental values for NMR order parameters and
      for dynamically averaged chemical shifts, suggesting that these simulations can
      be a productive platform for predicting the effects of individual amino acid
      residues on dynamic behavior. Analyses of the simulations reveal that a single
      residue differentiates between two different and otherwise conserved dynamic
      processes in a region of the protein known to form part of the substrate-binding
      interface. Additional key residues within these two categories are identified
      through the temperature-dependence of these conformational processes. 

PMID- 24098096
TI  - Swimming in light: a large-scale computational analysis of the metabolism of
      Dinoroseobacter shibae.
AB  - The Roseobacter clade is a ubiquitous group of marine alpha-proteobacteria. To
      gain insight into the versatile metabolism of this clade, we took a constraint
      based approach and created a genome-scale metabolic model (iDsh827) of
      Dinoroseobacter shibae DFL12T. Our model is the first accounting for the energy
      demand of motility, the light-driven ATP generation and experimentally determined
      specific biomass composition. To cover a large variety of environmental
      conditions, as well as plasmid and single gene knock-out mutants, we simulated
      391,560 different physiological states using flux balance analysis. We analyzed
      our results with regard to energy metabolism, validated them experimentally, and
      revealed a pronounced metabolic response to the availability of light.
      Furthermore, we introduced the energy demand of motility as an important
      parameter in genome-scale metabolic models. The results of our simulations also
      gave insight into the changing usage of the two degradation routes for
      dimethylsulfoniopropionate, an abundant compound in the ocean. A side product of
      dimethylsulfoniopropionate degradation is dimethyl sulfide, which seeds cloud
      formation and thus enhances the reflection of sunlight. By our exhaustive
      simulations, we were able to identify single-gene knock-out mutants, which show
      an increased production of dimethyl sulfide. In addition to the single-gene knock
      out simulations we studied the effect of plasmid loss on the metabolism.
      Moreover, we explored the possible use of a functioning phosphofructokinase for
      D. shibae. 

PMID- 24098098
TI  - ToPS: a framework to manipulate probabilistic models of sequence data.
AB  - Discrete Markovian models can be used to characterize patterns in sequences of
      values and have many applications in biological sequence analysis, including gene
      prediction, CpG island detection, alignment, and protein profiling. We present
      ToPS, a computational framework that can be used to implement different
      applications in bioinformatics analysis by combining eight kinds of models: (i)
      independent and identically distributed process; (ii) variable-length Markov
      chain; (iii) inhomogeneous Markov chain; (iv) hidden Markov model; (v) profile
      hidden Markov model; (vi) pair hidden Markov model; (vii) generalized hidden
      Markov model; and (viii) similarity based sequence weighting. The framework
      includes functionality for training, simulation and decoding of the models.
      Additionally, it provides two methods to help parameter setting: Akaike and
      Bayesian information criteria (AIC and BIC). The models can be used stand-alone,
      combined in Bayesian classifiers, or included in more complex, multi-model,
      probabilistic architectures using GHMMs. In particular the framework provides a
      novel, flexible, implementation of decoding in GHMMs that detects when the
      architecture can be traversed efficiently. 

PMID- 24098097
TI  - Sensitive detection of viral transcripts in human tumor transcriptomes.
AB  - In excess of 12% of human cancer incidents have a viral cofactor. Epidemiological
      studies of idiopathic human cancers indicate that additional tumor viruses remain
      to be discovered. Recent advances in sequencing technology have enabled
      systematic screenings of human tumor transcriptomes for viral transcripts.
      However, technical problems such as low abundances of viral transcripts in large
      volumes of sequencing data, viral sequence divergence, and homology between viral
      and human factors significantly confound identification of tumor viruses. We have
      developed a novel computational approach for detecting viral transcripts in human
      cancers that takes the aforementioned confounding factors into account and is
      applicable to a wide variety of viruses and tumors. We apply the approach to
      conducting the first systematic search for viruses in neuroblastoma, the most
      common cancer in infancy. The diverse clinical progression of this disease as
      well as related epidemiological and virological findings are highly suggestive of
      a pathogenic cofactor. However, a viral etiology of neuroblastoma is currently
      contested. We mapped 14 transcriptomes of neuroblastoma as well as positive and
      negative controls to the human and all known viral genomes in order to detect
      both known and unknown viruses. Analysis of controls, comparisons with related
      methods, and statistical estimates demonstrate the high sensitivity of our
      approach. Detailed investigation of putative viral transcripts within
      neuroblastoma samples did not provide evidence for the existence of any known
      human viruses. Likewise, de-novo assembly and analysis of chimeric transcripts
      did not result in expression signatures associated with novel human pathogens.
      While confounding factors such as sample dilution or viral clearance in
      progressed tumors may mask viral cofactors in the data, in principle, this is
      rendered less likely by the high sensitivity of our approach and the number of
      biological replicates analyzed. Therefore, our results suggest that frequent
      viral cofactors of metastatic neuroblastoma are unlikely.

PMID- 24098099
TI  - Ligand clouds around protein clouds: a scenario of ligand binding with
      intrinsically disordered proteins.
AB  - Intrinsically disordered proteins (IDPs) were found to be widely associated with
      human diseases and may serve as potential drug design targets. However, drug
      design targeting IDPs is still in the very early stages. Progress in drug design
      is usually achieved using experimental screening; however, the structural
      disorder of IDPs makes it difficult to characterize their interaction with
      ligands using experiments alone. To better understand the structure of IDPs and
      their interactions with small molecule ligands, we performed extensive
      simulations on the c-Myc370-409 peptide and its binding to a reported small
      molecule inhibitor, ligand 10074-A4. We found that the conformational space of
      the apo c-Myc370-409 peptide was rather dispersed and that the conformations of
      the peptide were stabilized mainly by charge interactions and hydrogen bonds.
      Under the binding of the ligand, c-Myc370-409 remained disordered. The ligand was
      found to bind to c-Myc370-409 at different sites along the chain and behaved like
      a 'ligand cloud'. In contrast to ligand binding to more rigid target proteins
      that usually results in a dominant bound structure, ligand binding to IDPs may
      better be described as ligand clouds around protein clouds. Nevertheless, the
      binding of the ligand and a non-ligand to the c-Myc370-409 target could be
      clearly distinguished. The present study provides insights that will help improve
      rational drug design that targets IDPs.

PMID- 24098100
TI  - The lazy visual word form area: computational insights into location-sensitivity.
AB  - In a recent study, Rauschecker et al. convincingly demonstrate that visual words
      evoke neural activation signals in the Visual Word Form Area that can be
      classified based on where they were presented in the visual fields. This result
      goes against the prevailing consensus, and begs an explanation. We show that one
      of the simplest possible models for word recognition, a multilayer feedforward
      network, will exhibit precisely the same behavior when trained to recognize words
      at different locations. The model suggests that the VWFA initially starts with
      information about location, which is not being suppressed during reading
      acquisition more than is needed to meet the requirements of location-invariant
      word recognition. Some new interpretations of Rauschecker et al.'s results are
      proposed, and three specific predictions are derived to be tested in further
      studies. 

PMID- 24098101
TI  - Cellular adaptation facilitates sparse and reliable coding in sensory pathways.
AB  - Most neurons in peripheral sensory pathways initially respond vigorously when a
      preferred stimulus is presented, but adapt as stimulation continues. It is
      unclear how this phenomenon affects stimulus coding in the later stages of
      sensory processing. Here, we show that a temporally sparse and reliable stimulus
      representation develops naturally in sequential stages of a sensory network with
      adapting neurons. As a modeling framework we employ a mean-field approach
      together with an adaptive population density treatment, accompanied by numerical
      simulations of spiking neural networks. We find that cellular adaptation plays a
      critical role in the dynamic reduction of the trial-by-trial variability of
      cortical spike responses by transiently suppressing self-generated fast
      fluctuations in the cortical balanced network. This provides an explanation for a
      widespread cortical phenomenon by a simple mechanism. We further show that in the
      insect olfactory system cellular adaptation is sufficient to explain the
      emergence of the temporally sparse and reliable stimulus representation in the
      mushroom body. Our results reveal a generic, biophysically plausible mechanism
      that can explain the emergence of a temporally sparse and reliable stimulus
      representation within a sequential processing architecture. 

PMID- 24098102
TI  - Target prediction for an open access set of compounds active against
      Mycobacterium tuberculosis.
AB  - Mycobacterium tuberculosis, the causative agent of tuberculosis (TB), infects an
      estimated two billion people worldwide and is the leading cause of mortality due
      to infectious disease. The development of new anti-TB therapeutics is required,
      because of the emergence of multi-drug resistance strains as well as co-infection
      with other pathogens, especially HIV. Recently, the pharmaceutical company
      GlaxoSmithKline published the results of a high-throughput screen (HTS) of their
      two million compound library for anti-mycobacterial phenotypes. The screen
      revealed 776 compounds with significant activity against the M. tuberculosis
      H37Rv strain, including a subset of 177 prioritized compounds with high potency
      and low in vitro cytotoxicity. The next major challenge is the identification of
      the target proteins. Here, we use a computational approach that integrates
      historical bioassay data, chemical properties and structural comparisons of
      selected compounds to propose their potential targets in M. tuberculosis. We
      predicted 139 target--compound links, providing a necessary basis for further
      studies to characterize the mode of action of these compounds. The results from
      our analysis, including the predicted structural models, are available to the
      wider scientific community in the open source mode, to encourage further
      development of novel TB therapeutics.

PMID- 24098103
TI  - Lipid receptor S1P1 activation scheme concluded from microsecond all-atom
      molecular dynamics simulations.
AB  - Sphingosine 1-phosphate (S1P) is a lysophospholipid mediator which activates G
      protein-coupled sphingosine 1-phosphate receptors and thus evokes a variety of
      cell and tissue responses including lymphocyte trafficking, endothelial
      development, integrity, and maturation. We performed five all-atom 700 ns
      molecular dynamics simulations of the sphingosine 1-phosphate receptor 1 (S1P1)
      based on recently released crystal structure of that receptor with an antagonist.
      We found that the initial movements of amino acid residues occurred in the area
      of highly conserved W2696.48 in TM6 which is close to the ligand binding
      location. Those residues located in the central part of the receptor and adjacent
      to kinks of TM helices comprise of a transmission switch. Side chains movements
      of those residues were coupled to the movements of water molecules inside the
      receptor which helped in the gradual opening of intracellular part of the
      receptor. The most stable parts of the protein were helices TM1 and TM2, while
      the largest movement was observed for TM7, possibly due to the short
      intracellular part starting with a helix kink at P7.50, which might be the first
      helix to move at the intracellular side. We show for the first time the detailed
      view of the concerted action of the transmission switch and Trp (W6.48) rotamer
      toggle switch leading to redirection of water molecules flow in the central part
      of the receptor. That event is a prerequisite for subsequent changes in
      intracellular part of the receptor involving water influx and opening of the
      receptor structure.

PMID- 24098104
TI  - How Can PLoS Computational Biology help the biological sciences?

PMID- 24098107
TI  - The regional student group program of the ISCB student council: stories from the
      road.
AB  - The International Society for Computational Biology (ISCB) Student Council was
      launched in 2004 to facilitate interaction between young scientists in the fields
      of bioinformatics and computational biology. Since then, the Student Council has
      successfully run events and programs to promote the development of the next
      generation of computational biologists. However, in its early years, the Student
      Council faced a major challenge, in that students from different geographical
      regions had different needs; no single activity or event could address the needs
      of all students. To overcome this challenge, the Student Council created the
      Regional Student Group (RSG) program. The program consists of locally organised
      and run student groups that address the specific needs of students in their
      region. These groups usually encompass a given country, and, via affiliation with
      the international Student Council, are provided with financial support,
      organisational support, and the ability to share information with other RSGs. In
      the last five years, RSGs have been created all over the world and organised
      activities that have helped develop dynamic bioinformatics student communities.
      In this article series, we present common themes emerging from RSG initiatives,
      explain their goals, and highlight the challenges and rewards through specific
      examples. This article, the first in the series, introduces the Student Council
      and provides a high-level overview of RSG activities. Our hope is that the
      article series will be a valuable source of information and inspiration for
      initiating similar activities in other regions and scientific communities. 

PMID- 24098108
TI  - Dengue vaccines: strongly sought but not a reality just yet.

PMID- 24098105
TI  - Balanced excitatory and inhibitory synaptic currents promote efficient coding and
      metabolic efficiency.
AB  - A balance between excitatory and inhibitory synaptic currents is thought to be
      important for several aspects of information processing in cortical neurons in
      vivo, including gain control, bandwidth and receptive field structure. These
      factors will affect the firing rate of cortical neurons and their reliability,
      with consequences for their information coding and energy consumption. Yet how
      balanced synaptic currents contribute to the coding efficiency and energy
      efficiency of cortical neurons remains unclear. We used single compartment
      computational models with stochastic voltage-gated ion channels to determine
      whether synaptic regimes that produce balanced excitatory and inhibitory currents
      have specific advantages over other input regimes. Specifically, we compared
      models with only excitatory synaptic inputs to those with equal excitatory and
      inhibitory conductances, and stronger inhibitory than excitatory conductances
      (i.e. approximately balanced synaptic currents). Using these models, we show that
      balanced synaptic currents evoke fewer spikes per second than excitatory inputs
      alone or equal excitatory and inhibitory conductances. However, spikes evoked by
      balanced synaptic inputs are more informative (bits/spike), so that spike trains
      evoked by all three regimes have similar information rates (bits/s).
      Consequently, because spikes dominate the energy consumption of our computational
      models, approximately balanced synaptic currents are also more energy efficient
      than other synaptic regimes. Thus, by producing fewer, more informative spikes
      approximately balanced synaptic currents in cortical neurons can promote both
      coding efficiency and energy efficiency. 

PMID- 24098109
TI  - Feeding uninvited guests: mTOR and AMPK set the table for intracellular
      pathogens.

PMID- 24098111
TI  - Chemicals, climate, and control: increasing the effectiveness of malaria vector
      control tools by considering relevant temperatures.

PMID- 24098112
TI  - Glycogen metabolic genes are involved in trehalose-6-phosphate synthase-mediated
      regulation of pathogenicity by the rice blast fungus Magnaporthe oryzae.
AB  - The filamentous fungus Magnaporthe oryzae is the causal agent of rice blast
      disease. Here we show that glycogen metabolic genes play an important role in
      plant infection by M. oryzae. Targeted deletion of AGL1 and GPH1, which encode
      amyloglucosidase and glycogen phosphorylase, respectively, prevented mobilisation
      of glycogen stores during appressorium development and caused a significant
      reduction in the ability of M. oryzae to cause rice blast disease. By contrast,
      targeted mutation of GSN1, which encodes glycogen synthase, significantly reduced
      the synthesis of intracellular glycogen, but had no effect on fungal
      pathogenicity. We found that loss of AGL1 and GPH1 led to a reduction in
      expression of TPS1 and TPS3, which encode components of the trehalose-6-phosphate
      synthase complex, that acts as a genetic switch in M. oryzae. Tps1 responds to
      glucose-6-phosphate levels and the balance of NADP/NADPH to regulate virulence
      associated gene expression, in association with Nmr transcriptional inhibitors.
      We show that deletion of the NMR3 transcriptional inhibitor gene partially
      restores virulence to a Deltaagl1Deltagph1 mutant, suggesting that glycogen
      metabolic genes are necessary for operation of the NADPH-dependent genetic switch
      in M. oryzae. 

PMID- 24098110
TI  - Kinetics of myeloid dendritic cell trafficking and activation: impact on
      progressive, nonprogressive and controlled SIV infections.
AB  - We assessed the role of myeloid dendritic cells (mDCs) in the outcome of SIV
      infection by comparing and contrasting their frequency, mobilization, phenotype,
      cytokine production and apoptosis in pathogenic (pigtailed macaques, PTMs),
      nonpathogenic (African green monkeys, AGMs) and controlled (rhesus macaques, RMs)
      SIVagmSab infection. Through the identification of recently replicating cells, we
      demonstrated that mDC mobilization from the bone marrow occurred in all species
      postinfection, being most prominent in RMs. Circulating mDCs were depleted with
      disease progression in PTMs, recovered to baseline values after the viral peak in
      AGMs, and significantly increased at the time of virus control in RMs. Rapid
      disease progression in PTMs was associated with low baseline levels and
      incomplete recovery of circulating mDCs during chronic infection. mDC recruitment
      to the intestine occurred in all pathogenic scenarios, but loss of mucosal mDCs
      was associated only with progressive infection. Sustained mDC immune activation
      occurred throughout infection in PTMs and was associated with increased bystander
      apoptosis in blood and intestine. Conversely, mDC activation occurred only during
      acute infection in nonprogressive and controlled infections. Postinfection,
      circulating mDCs rapidly became unresponsive to TLR7/8 stimulation in all
      species. Yet, stimulation with LPS, a bacterial product translocated in
      circulation only in SIV-infected PTMs, induced mDC hyperactivation, apoptosis and
      excessive production of proinflammatory cytokines. After infection, spontaneous
      production of proinflammatory cytokines by mucosal mDCs increased only in
      progressor PTMs. We thus propose that mDCs promote tolerance to SIV in the
      biological systems that lack intestinal dysfunction. In progressive infections,
      mDC loss and excessive activation of residual mDCs by SIV and additional stimuli,
      such as translocated microbial products, enhance generalized immune activation
      and inflammation. Our results thus provide a mechanistic basis for the role of
      mDCs in the pathogenesis of AIDS and elucidate the causes of mDC loss during
      progressive HIV/SIV infections. 

PMID- 24098113
TI  - Role of the Vibrio cholerae matrix protein Bap1 in cross-resistance to
      antimicrobial peptides.
AB  - Outer membrane vesicles (OMVs) that are released from Gram-negative pathogenic
      bacteria can serve as vehicles for the translocation of effectors involved in
      infectious processes. In this study we have investigated the role of OMVs of the
      Vibrio cholerae O1 El Tor A1552 strain in resistance to antimicrobial peptides
      (AMPs). To assess this potential role, we grew V. cholerae with sub-lethal
      concentrations of Polymyxin B (PmB) or the AMP LL-37 and analyzed the OMVs
      produced and their effects on AMP resistance. Our results show that growing V.
      cholerae in the presence of AMPs modifies the protein content of the OMVs. In the
      presence of PmB, bacteria release OMVs that are larger in size and contain a
      biofilm-associated extracellular matrix protein (Bap1). We demonstrated that Bap1
      binds to the OmpT porin on the OMVs through the LDV domain of OmpT. In addition,
      OMVs from cultures incubated in presence of PmB also provide better protection
      for V. cholerae against LL-37 compared to OMVs from V. cholerae cultures grown
      without AMPs or in presence of LL-37. Using a bap1 mutant we showed that cross
      resistance between PmB and LL-37 involved the Bap1 protein, whereby Bap1 on OMVs
      traps LL-37 with no subsequent degradation of the AMP. 

PMID- 24098115
TI  - APOBEC3G polymorphism as a selective barrier to cross-species transmission and
      emergence of pathogenic SIV and AIDS in a primate host.
AB  - Cellular restriction factors, which render cells intrinsically resistant to
      viruses, potentially impose genetic barriers to cross-species transmission and
      emergence of viral pathogens in nature. One such factor is APOBEC3G. To overcome
      APOBEC3G-mediated restriction, many lentiviruses encode Vif, a protein that
      targets APOBEC3G for degradation. As with many restriction factor genes, primate
      APOBEC3G displays strong signatures of positive selection. This is interpreted as
      evidence that the primate APOBEC3G locus reflects a long-term evolutionary "arms
      race" between retroviruses and their primate hosts. Here, we provide direct
      evidence that APOBEC3G has functioned as a barrier to cross-species transmission,
      selecting for viral resistance during emergence of the AIDS-causing pathogen
      SIVmac in captive colonies of Asian macaques in the 1970s. Specifically, we found
      that rhesus macaques have multiple, functionally distinct APOBEC3G alleles, and
      that emergence of SIVmac and simian AIDS required adaptation of the virus to
      evade APOBEC3G-mediated restriction. Our evidence includes the first comparative
      analysis of APOBEC3G polymorphism and function in both a reservoir and recipient
      host species (sooty mangabeys and rhesus macaques, respectively), and
      identification of adaptations unique to Vif proteins of the SIVmac lineage that
      specifically antagonize rhesus APOBEC3G alleles. By demonstrating that
      interspecies variation in a known restriction factor selected for viral counter
      adaptations in the context of a documented case of cross-species transmission,
      our results lend strong support to the evolutionary "arms-race" hypothesis.
      Importantly, our study confirms that APOBEC3G divergence can be a critical
      determinant of interspecies transmission and emergence of primate lentiviruses,
      including viruses with the potential to infect and spread in human populations. 

PMID- 24098114
TI  - NADPH oxidase-driven phagocyte recruitment controls Candida albicans filamentous
      growth and prevents mortality.
AB  - Candida albicans is a human commensal and clinically important fungal pathogen
      that grows as both yeast and hyphal forms during human, mouse and zebrafish
      infection. Reactive oxygen species (ROS) produced by NADPH oxidases play diverse
      roles in immunity, including their long-appreciated function as microbicidal
      oxidants. Here we demonstrate a non-traditional mechanistic role of NADPH oxidase
      in promoting phagocyte chemotaxis and intracellular containment of fungi to limit
      filamentous growth. We exploit the transparent zebrafish model to show that
      failed NADPH oxidase-dependent phagocyte recruitment to C. albicans in the first
      four hours post-infection permits fungi to germinate extracellularly and kill the
      host. We combine chemical and genetic tools with high-resolution time-lapse
      microscopy to implicate both phagocyte oxidase and dual-specific oxidase in
      recruitment, suggesting that both myeloid and non-myeloid cells promote
      chemotaxis. We show that early non-invasive imaging provides a robust tool for
      prognosis, strongly connecting effective early immune response with survival.
      Finally, we demonstrate a new role of a key regulator of the yeast-to-hyphal
      switching program in phagocyte-mediated containment, suggesting that there are
      species-specific methods for modulation of NADPH oxidase-independent immune
      responses. These novel links between ROS-driven chemotaxis and fungal dimorphism
      expand our view of a key host defense mechanism and have important implications
      for pathogenesis. 

PMID- 24098116
TI  - The role of TcdB and TccC subunits in secretion of the Photorhabdus Tcd toxin
      complex.
AB  - The Toxin Complex (TC) is a large multi-subunit toxin encoded by a range of
      bacterial pathogens. The best-characterized examples are from the insect
      pathogens Photorhabdus, Xenorhabdus and Yersinia. They consist of three large
      protein subunits, designated A, B and C that assemble in a 5?1?1 stoichiometry.
      Oral toxicity to a range of insects means that some have the potential to be
      developed as pest control technology. The three subunit proteins do not encode
      any recognisable export sequences and as such little progress has been made in
      understanding their secretion. We have developed heterologous TC production and
      secretion models in E. coli and used them to ascribe functions to different
      domains of the crucial B+C sub-complex. We have determined that the B and C
      subunits use a secretion mechanism that is either encoded by the proteins
      themselves or employ an as yet undefined system common to laboratory strains of
      E. coli. We demonstrate that both the N-terminal domains of the B and C subunits
      are required for secretion of the whole complex. We propose a model whereby the N
      terminus of the C-subunit toxin exports the B+C sub-complex across the inner
      membrane while that of the B-subunit allows passage across the outer membrane. We
      also demonstrate that even in the absence of the B-subunit, that the C-subunit
      can also facilitate secretion of the larger A-subunit. The recognition of this
      novel export system is likely to be of importance to future protein secretion
      studies. Finally, the identification of homologues of B and C subunits in diverse
      bacterial pathogens, including Burkholderia and Pseudomonas, suggests that these
      toxins are likely to be important in a range of different hosts, including man. 

PMID- 24098117
TI  - TXNIP deficiency exacerbates endotoxic shock via the induction of excessive
      nitric oxide synthesis.
AB  - Thioredoxin-interacting protein (TXNIP) has multiple functions, including tumor
      suppression and involvement in cell proliferation and apoptosis. However, its
      role in the inflammatory process remains unclear. In this report, we demonstrate
      that Txnip-/- mice are significantly more susceptible to lipopolysaccharide (LPS)
      induced endotoxic shock. In response to LPS, Txnip-/- macrophages produced
      significantly higher levels of nitric oxide (NO) and inducible nitric oxide
      synthase (iNOS), and an iNOS inhibitor rescued Txnip-/- mice from endotoxic shock
      induced death, demonstrating that NO is a major factor in TXNIP-mediated
      endotoxic shock. This susceptibility phenotype of Txnip-/- mice occurred despite
      reduced IL-1beta secretion due to increased S-nitrosylation of NLRP3 compared to
      wild-type controls. Taken together, these data demonstrate that TXNIP is a novel
      molecule that links NO synthesis and NLRP3 inflammasome activation during
      endotoxic shock.

PMID- 24098118
TI  - A mechanism for the inhibition of DNA-PK-mediated DNA sensing by a virus.
AB  - The innate immune system is critical in the response to infection by pathogens
      and it is activated by pattern recognition receptors (PRRs) binding to pathogen
      associated molecular patterns (PAMPs). During viral infection, the direct
      recognition of the viral nucleic acids, such as the genomes of DNA viruses, is
      very important for activation of innate immunity. Recently, DNA-dependent protein
      kinase (DNA-PK), a heterotrimeric complex consisting of the Ku70/Ku80 heterodimer
      and the catalytic subunit DNA-PKcs was identified as a cytoplasmic PRR for DNA
      that is important for the innate immune response to intracellular DNA and DNA
      virus infection. Here we show that vaccinia virus (VACV) has evolved to inhibit
      this function of DNA-PK by expression of a highly conserved protein called C16,
      which was known to contribute to virulence but by an unknown mechanism. Data
      presented show that C16 binds directly to the Ku heterodimer and thereby inhibits
      the innate immune response to DNA in fibroblasts, characterised by the decreased
      production of cytokines and chemokines. Mechanistically, C16 acts by blocking DNA
      PK binding to DNA, which correlates with reduced DNA-PK-dependent DNA sensing.
      The C-terminal region of C16 is sufficient for binding Ku and this activity is
      conserved in the variola virus (VARV) orthologue of C16. In contrast, deletion of
      5 amino acids in this domain is enough to knockout this function from the
      attenuated vaccine strain modified vaccinia virus Ankara (MVA). In vivo a VACV
      mutant lacking C16 induced higher levels of cytokines and chemokines early after
      infection compared to control viruses, confirming the role of this virulence
      factor in attenuating the innate immune response. Overall this study describes
      the inhibition of DNA-PK-dependent DNA sensing by a poxvirus protein, adding to
      the evidence that DNA-PK is a critical component of innate immunity to DNA
      viruses. 

PMID- 24098119
TI  - Herpes simplex virus type 1 single strand DNA binding protein and
      helicase/primase complex disable cellular ATR signaling.
AB  - Herpes Simplex Virus type 1 (HSV-1) has evolved to disable the cellular DNA
      damage response kinase, ATR. We have previously shown that HSV-1-infected cells
      are unable to phosphorylate the ATR substrate Chk1, even under conditions in
      which replication forks are stalled. Here we report that the HSV-1 single
      stranded DNA binding protein (ICP8), and the helicase/primase complex
      (UL8/UL5/UL52) form a nuclear complex in transfected cells that is necessary and
      sufficient to disable ATR signaling. This complex localizes to sites of DNA
      damage and colocalizes with ATR/ATRIP and RPA, but under these conditions, the
      Rad9-Rad1-Hus1 checkpoint clamp (9-1-1) do not. ATR is generally activated by
      substrates that contain ssDNA adjacent to dsDNA, and previous work from our
      laboratory has shown that ICP8 and helicase/primase also recognize this
      substrate. We suggest that these four viral proteins prevent ATR activation by
      binding to the DNA substrate and obstructing loading of the 9-1-1 checkpoint
      clamp. Exclusion of 9-1-1 prevents recruitment of TopBP1, the ATR kinase
      activator, and thus effectively disables ATR signaling. These data provide the
      first example of viral DNA replication proteins obscuring access to a DNA
      substrate that would normally trigger a DNA damage response and checkpoint
      signaling. This unusual mechanism used by HSV suggests that it may be possible to
      inhibit ATR signaling by preventing recruitment of the 9-1-1 clamp and TopBP1. 

PMID- 24098120
TI  - Type I J-domain NbMIP1 proteins are required for both Tobacco mosaic virus
      infection and plant innate immunity.
AB  - Tm-22 is a coiled coil-nucleotide binding-leucine rich repeat resistance protein
      that confers durable extreme resistance against Tomato mosaic virus (ToMV) and
      Tobacco mosaic virus (TMV) by recognizing the viral movement protein (MP). Here
      we report that the Nicotiana benthamiana J-domain MIP1 proteins (NbMIP1s)
      associate with tobamovirus MP, Tm-22 and SGT1. Silencing of NbMIP1s reduced TMV
      movement and compromised Tm-22-mediated resistance against TMV and ToMV.
      Furthermore, silencing of NbMIP1s reduced the steady-state protein levels of ToMV
      MP and Tm-22. Moreover, NbMIP1s are required for plant resistance induced by
      other R genes and the nonhost pathogen Pseudomonas syringae pv. tomato (Pst)
      DC3000. In addition, we found that SGT1 associates with Tm-22 and is required for
      Tm-22-mediated resistance against TMV. These results suggest that NbMIP1s
      function as co-chaperones during virus infection and plant immunity.

PMID- 24098121
TI  - Sequestration by IFIT1 impairs translation of 2'O-unmethylated capped RNA.
AB  - Viruses that generate capped RNA lacking 2'O methylation on the first ribose are
      severely affected by the antiviral activity of Type I interferons. We used
      proteome-wide affinity purification coupled to mass spectrometry to identify
      human and mouse proteins specifically binding to capped RNA with different
      methylation states. This analysis, complemented with functional validation
      experiments, revealed that IFIT1 is the sole interferon-induced protein
      displaying higher affinity for unmethylated than for methylated capped RNA. IFIT1
      tethers a species-specific protein complex consisting of other IFITs to RNA.
      Pulsed stable isotope labelling with amino acids in cell culture coupled to mass
      spectrometry as well as in vitro competition assays indicate that IFIT1
      sequesters 2'O-unmethylated capped RNA and thereby impairs binding of eukaryotic
      translation initiation factors to 2'O-unmethylated RNA template, which results in
      inhibition of translation. The specificity of IFIT1 for 2'O-unmethylated RNA
      serves as potent antiviral mechanism against viruses lacking 2'O
      methyltransferase activity and at the same time allows unperturbed progression of
      the antiviral program in infected cells. 

PMID- 24098122
TI  - Ehrlichia chaffeensis uses its surface protein EtpE to bind GPI-anchored protein
      DNase X and trigger entry into mammalian cells.
AB  - Ehrlichia chaffeensis, an obligatory intracellular rickettsial pathogen, enters
      and replicates in monocytes/macrophages and several non-phagocytic cells. E.
      chaffeensis entry into mammalian cells is essential not only for causing the
      emerging zoonosis, human monocytic ehrlichiosis, but also for its survival. It
      remains unclear if E. chaffeensis has evolved a specific surface protein that
      functions as an 'invasin' to mediate its entry. We report a novel entry
      triggering protein of Ehrlichia, EtpE that functions as an invasin. EtpE is an
      outer membrane protein and an antibody against EtpE (the C-terminal fragment,
      EtpE-C) greatly inhibited E. chaffeensis binding, entry and infection of both
      phagocytes and non-phagocytes. EtpE-C-immunization of mice significantly
      inhibited E. chaffeensis infection. EtpE-C-coated latex beads, used to
      investigate whether EtpE-C can mediate cell invasion, entered both phagocytes and
      non-phagocytes and the entry was blocked by compounds that block E. chaffeensis
      entry. None of these compounds blocked uptake of non-coated beads by phagocytes.
      Yeast two-hybrid screening revealed that DNase X, a glycosylphosphatidyl inositol
      anchored mammalian cell-surface protein binds EtpE-C. This was confirmed by far
      Western blotting, affinity pull-down, co-immunoprecipitation, immunofluorescence
      labeling, and live-cell image analysis. EtpE-C-coated beads entered bone marrow
      derived macrophages (BMDMs) from wild-type mice, whereas they neither bound nor
      entered BMDMs from DNase X(-/-) mice. Antibody against DNase X or DNase X knock
      down by small interfering RNA impaired E. chaffeensis binding, entry, and
      infection. E. chaffeensis entry and infection rates of BMDMs from DNase X(-/-)
      mice and bacterial load in the peripheral blood in experimentally infected DNase
      X(-/-) mice, were significantly lower than those from wild-type mice. Thus this
      obligatory intracellular pathogen evolved a unique protein EtpE that binds DNase
      X to enter and infect eukaryotic cells. This study is the first to demonstrate
      the invasin and its mammalian receptor, and their in vivo relevance in any
      ehrlichial species. 

PMID- 24098123
TI  - Salmonella modulation of host cell gene expression promotes its intracellular
      growth.
AB  - Salmonella Typhimurium has evolved a complex functional interface with its host
      cell largely determined by two type III secretion systems (T3SS), which through
      the delivery of bacterial effector proteins modulate a variety of cellular
      processes. We show here that Salmonella Typhimurium infection of epithelial cells
      results in a profound transcriptional reprogramming that changes over time. This
      response is triggered by Salmonella T3SS effector proteins, which stimulate
      unique signal transduction pathways leading to STAT3 activation. We found that
      the Salmonella-stimulated changes in host cell gene expression are required for
      the formation of its specialized vesicular compartment that is permissive for its
      intracellular replication. This study uncovers a cell-autonomous process required
      for Salmonella pathogenesis potentially opening up new avenues for the
      development of anti-infective strategies that target relevant host pathways. 

PMID- 24098124
TI  - Loss of the TGFbeta-activating integrin alphavbeta8 on dendritic cells protects
      mice from chronic intestinal parasitic infection via control of type 2 immunity.
AB  - Chronic intestinal parasite infection is a major global health problem, but
      mechanisms that promote chronicity are poorly understood. Here we describe a
      novel cellular and molecular pathway involved in the development of chronic
      intestinal parasite infection. We show that, early during development of chronic
      infection with the murine intestinal parasite Trichuris muris, TGFbeta signalling
      in CD4+ T-cells is induced and that antibody-mediated inhibition of TGFbeta
      function results in protection from infection. Mechanistically, we find that
      enhanced TGFbeta signalling in CD4+ T-cells during infection involves expression
      of the TGFbeta-activating integrin alphavbeta8 by dendritic cells (DCs), which we
      have previously shown is highly expressed by a subset of DCs in the intestine.
      Importantly, mice lacking integrin alphavbeta8 on DCs were completely resistant
      to chronic infection with T. muris, indicating an important functional role for
      integrin alphavbeta8-mediated TGFbeta activation in promoting chronic infection.
      Protection from infection was dependent on CD4+ T-cells, but appeared independent
      of Foxp3+ Tregs. Instead, mice lacking integrin alphavbeta8 expression on DCs
      displayed an early increase in production of the protective type 2 cytokine IL-13
      by CD4+ T-cells, and inhibition of this increase by crossing mice to IL-4
      knockout mice restored parasite infection. Our results therefore provide novel
      insights into how type 2 immunity is controlled in the intestine, and may help
      contribute to development of new therapies aimed at promoting expulsion of gut
      helminths. 

PMID- 24098125
TI  - Inhibition of pyrimidine biosynthesis pathway suppresses viral growth through
      innate immunity.
AB  - Searching for stimulators of the innate antiviral response is an appealing
      approach to develop novel therapeutics against viral infections. Here, we
      established a cell-based reporter assay to identify compounds stimulating
      expression of interferon-inducible antiviral genes. DD264 was selected out of
      41,353 compounds for both its immuno-stimulatory and antiviral properties. While
      searching for its mode of action, we identified DD264 as an inhibitor of
      pyrimidine biosynthesis pathway. This metabolic pathway was recently identified
      as a prime target of broad-spectrum antiviral molecules, but our data unraveled a
      yet unsuspected link with innate immunity. Indeed, we showed that DD264 or
      brequinar, a well-known inhibitor of pyrimidine biosynthesis pathway, both
      enhanced the expression of antiviral genes in human cells. Furthermore, antiviral
      activity of DD264 or brequinar was found strictly dependent on cellular gene
      transcription, nuclear export machinery, and required IRF1 transcription factor.
      In conclusion, the antiviral property of pyrimidine biosynthesis inhibitors is
      not a direct consequence of pyrimidine deprivation on the virus machinery, but
      rather involves the induction of cellular immune response. 

PMID- 24098126
TI  - Early host cell targets of Yersinia pestis during primary pneumonic plague.
AB  - Inhalation of Yersinia pestis causes primary pneumonic plague, a highly lethal
      syndrome with mortality rates approaching 100%. Pneumonic plague progression is
      biphasic, with an initial pre-inflammatory phase facilitating bacterial growth in
      the absence of host inflammation, followed by a pro-inflammatory phase marked by
      extensive neutrophil influx, an inflammatory cytokine storm, and severe tissue
      destruction. Using a FRET-based probe to quantitate injection of effector
      proteins by the Y. pestis type III secretion system, we show that these bacteria
      target alveolar macrophages early during infection of mice, followed by a switch
      in host cell preference to neutrophils. We also demonstrate that neutrophil
      influx is unable to limit bacterial growth in the lung and is ultimately
      responsible for the severe inflammation during the lethal pro-inflammatory phase.

PMID- 24098127
TI  - Bacterial pathogens activate a common inflammatory pathway through IFNlambda
      regulation of PDCD4.
AB  - The type III interferon (IFNlambda) receptor IL-28R is abundantly expressed in
      the respiratory tract and has been shown essential for host defense against some
      viral pathogens, however no data are available concerning its role in the innate
      immune response to bacterial pathogens. Staphylococcus aureus and Pseudomonas
      aeruginosa induced significant production of IFNlambda in the lung, and clearance
      of these bacteria from the lung was significantly increased in IL-28R null mice
      compared to controls. Improved bacterial clearance correlated with reduced lung
      pathology and a reduced ratio of pro- vs anti-inflammatory cytokines in the
      airway. In human epithelial cells IFNlambda inhibited miR-21 via STAT3 resulting
      in upregulation of PDCD4, a protein known to promote inflammatory signaling. In
      vivo 18 hours following infection with either pathogen, miR-21 was significantly
      reduced and PDCD4 increased in the lungs of wild type compared to IL-28R null
      mice. Infection of PDCD4 null mice with USA300 resulted in improved clearance,
      reduced pathology, and reduced inflammatory cytokine production. These data
      suggest that during bacterial pneumonia IFNlambda promotes inflammation by
      inhibiting miR-21 regulation of PDCD4. 

PMID- 24098128
TI  - Contribution of host intracellular transport machineries to intercellular
      movement of turnip mosaic virus.
AB  - The contribution of different host cell transport systems in the intercellular
      movement of turnip mosaic virus (TuMV) was investigated. To discriminate between
      primary infections and secondary infections associated with the virus
      intercellular movement, a gene cassette expressing GFP-HDEL was inserted adjacent
      to a TuMV infectious cassette expressing 6K2:mCherry, both within the T-DNA
      borders of the binary vector pCambia. In this system, both gene cassettes were
      delivered to the same cell by a single binary vector and primary infection foci
      emitted green and red fluorescence while secondarily infected cells emitted only
      red fluorescence. Intercellular movement was measured at 72 hours post
      infiltration and was estimated to proceed at an average rate of one cell being
      infected every three hours over an observation period of 17 hours. To determine
      if the secretory pathway were important for TuMV intercellular movement, chemical
      and protein inhibitors that blocked both early and late secretory pathways were
      used. Treatment with Brefeldin A or Concanamycin A or expression of ARF1 or RAB
      E1d dominant negative mutants, all of which inhibit pre- or post-Golgi transport,
      reduced intercellular movement by the virus. These treatments, however, did not
      inhibit virus replication in primary infected cells. Pharmacological interference
      assays using Tyrphostin A23 or Wortmannin showed that endocytosis was not
      important for TuMV intercellular movement. Lack of co-localization by endocytosed
      FM4-64 and Ara7 (AtRabF2b) with TuMV-induced 6K2-tagged vesicles further
      supported this conclusion. Microfilament depolymerizing drugs and silencing
      expression of myosin XI-2 gene, but not myosin VIII genes, also inhibited TuMV
      intercellular movement. Expression of dominant negative myosin mutants confirmed
      the role played by myosin XI-2 as well as by myosin XI-K in TuMV intercellular
      movement. Using this dual gene cassette expression system and transport
      inhibitors, components of the secretory and actomyosin machinery were shown to be
      important for TuMV intercellular spread.

PMID- 24098129
TI  - The TgsGP gene is essential for resistance to human serum in Trypanosoma brucei
      gambiense.
AB  - Trypanosoma brucei gambiense causes 97% of all cases of African sleeping
      sickness, a fatal disease of sub-Saharan Africa. Most species of trypanosome,
      such as T. b. brucei, are unable to infect humans due to the trypanolytic serum
      protein apolipoprotein-L1 (APOL1) delivered via two trypanosome lytic factors
      (TLF-1 and TLF-2). Understanding how T. b. gambiense overcomes these factors and
      infects humans is of major importance in the fight against this disease. Previous
      work indicated that a failure to take up TLF-1 in T. b. gambiense contributes to
      resistance to TLF-1, although another mechanism is required to overcome TLF-2.
      Here, we have examined a T. b. gambiense specific gene, TgsGP, which had
      previously been suggested, but not shown, to be involved in serum resistance. We
      show that TgsGP is essential for resistance to lysis as deletion of TgsGP in T.
      b. gambiense renders the parasites sensitive to human serum and recombinant
      APOL1. Deletion of TgsGP in T. b. gambiense modified to uptake TLF-1 showed
      sensitivity to TLF-1, APOL1 and human serum. Reintroducing TgsGP into knockout
      parasite lines restored resistance. We conclude that TgsGP is essential for human
      serum resistance in T. b. gambiense. 

PMID- 24098130
TI  - Massive depletion of bovine leukemia virus proviral clones located in genomic
      transcriptionally active sites during primary infection.
AB  - Deltaretroviruses such as human T-lymphotropic virus type 1 (HTLV-1) and bovine
      leukemia virus (BLV) induce a persistent infection that remains generally
      asymptomatic but can also lead to leukemia or lymphoma. These viruses replicate
      by infecting new lymphocytes (i.e. the infectious cycle) or via clonal expansion
      of the infected cells (mitotic cycle). The relative importance of these two
      cycles in viral replication varies during infection. The majority of infected
      clones are created early before the onset of an efficient immune response. Later
      on, the main replication route is mitotic expansion of pre-existing infected
      clones. Due to the paucity of available samples and for ethical reasons, only
      scarce data is available on early infection by HTLV-1. Therefore, we addressed
      this question in a comparative BLV model. We used high-throughput sequencing to
      map and quantify the insertion sites of the provirus in order to monitor the
      clonality of the BLV-infected cells population (i.e. the number of distinct
      clones and abundance of each clone). We found that BLV propagation shifts from
      cell neoinfection to clonal proliferation in about 2 months from inoculation.
      Initially, BLV proviral integration significantly favors transcribed regions of
      the genome. Negative selection then eliminates 97% of the clones detected at
      seroconversion and disfavors BLV-infected cells carrying a provirus located close
      to a promoter or a gene. Nevertheless, among the surviving proviruses, clone
      abundance positively correlates with proximity of the provirus to a transcribed
      region. Two opposite forces thus operate during primary infection and dictate the
      fate of long term clonal composition: (1) initial integration inside genes or
      promoters and (2) host negative selection disfavoring proviruses located next to
      transcribed regions. The result of this initial response will contribute to the
      proviral load set point value as clonal abundance will benefit from carrying a
      provirus in transcribed regions. 

PMID- 24098134
TI  - A new class of quorum quenching molecules from Staphylococcus species affects
      communication and growth of gram-negative bacteria.
AB  - The knowledge that many pathogens rely on cell-to-cell communication mechanisms
      known as quorum sensing, opens a new disease control strategy: quorum quenching.
      Here we report on one of the rare examples where Gram-positive bacteria, the
      'Staphylococcus intermedius group' of zoonotic pathogens, excrete two compounds
      in millimolar concentrations that suppress the quorum sensing signaling and
      inhibit the growth of a broad spectrum of Gram-negative beta- and gamma
      proteobacteria. These compounds were isolated from Staphylococcus delphini. They
      represent a new class of quorum quenchers with the chemical formula N-[2-(1H
      indol-3-yl)ethyl]-urea and N-(2-phenethyl)-urea, which we named yayurea A and B,
      respectively. In vitro studies with the N-acyl homoserine lactone (AHL)
      responding receptor LuxN of V. harveyi indicated that both compounds caused
      opposite effects on phosphorylation to those caused by AHL. This explains the
      quorum quenching activity. Staphylococcal strains producing yayurea A and B
      clearly benefit from an increased competitiveness in a mixed community. 

PMID- 24098135
TI  - Conserved translatome remodeling in nematode species executing a shared
      developmental transition.
AB  - Nematodes of the genus Caenorhabditis enter a developmental diapause state after
      hatching in the absence of food. To better understand the relative contributions
      of distinct regulatory modalities to gene expression changes associated with this
      developmental transition, we characterized genome-wide changes in mRNA abundance
      and translational efficiency associated with L1 diapause exit in four species
      using ribosome profiling and mRNA-seq. We found a strong tendency for
      translational regulation and mRNA abundance processes to act synergistically,
      together effecting a dramatic remodeling of the gene expression program. While
      gene-specific differences were observed between species, overall translational
      dynamics were broadly and functionally conserved. A striking, conserved feature
      of the response was strong translational suppression of ribosomal protein
      production during L1 diapause, followed by activation upon resumed development.
      On a global scale, ribosome footprint abundance changes showed greater similarity
      between species than changes in mRNA abundance, illustrating a substantial and
      genome-wide contribution of translational regulation to evolutionary maintenance
      of stable gene expression. 

PMID- 24098136
TI  - A novel actin mRNA splice variant regulates ACTG1 expression.
AB  - Cytoplasmic actins are abundant, ubiquitous proteins in nucleated cells. However,
      actin expression is regulated in a tissue- and development-specific manner. We
      identified a novel cytoplasmic-gamma-actin (Actg1) transcript that includes a
      previously unidentified exon (3a). Inclusion of this exon introduces an in-frame
      termination codon. We hypothesized this alternatively-spliced transcript down
      regulates gamma-actin production by targeting these transcripts for nonsense
      mediated decay (NMD). To address this, we investigated conservation between
      mammals, tissue-specificity in mice, and developmental regulation using C2C12
      cell culture. Exon 3a is 80% similar among mammals and varies in length from 41
      nucleotides in humans to 45 in mice. Though the predicted amino acid sequences
      are not similar between all species, inclusion of exon 3a consistently results in
      the in the introduction of a premature termination codon within the alternative
      Actg1 transcript. Of twelve tissues examined, exon 3a is predominantly expressed
      in skeletal muscle, cardiac muscle, and diaphragm. Splicing to include exon 3a is
      concomitant with previously described down-regulation of Actg1 in differentiating
      C2C12 cells. Treatment of differentiated C2C12 cells with an inhibitor of NMD
      results in a 7-fold increase in exon 3a-containing transcripts. Therefore,
      splicing to generate exon 3a-containing transcripts may be one component of Actg1
      regulation. We propose that this post-transcriptional regulation occurs via NMD,
      in a process previously described as "regulated unproductive splicing and
      translation" (RUST). 

PMID- 24098137
TI  - Genome-wide analysis of cell type-specific gene transcription during spore
      formation in Clostridium difficile.
AB  - Clostridium difficile, a Gram positive, anaerobic, spore-forming bacterium is an
      emergent pathogen and the most common cause of nosocomial diarrhea. Although
      transmission of C. difficile is mediated by contamination of the gut by spores,
      the regulatory cascade controlling spore formation remains poorly characterized.
      During Bacillus subtilis sporulation, a cascade of four sigma factors, sigma(F)
      and sigma(G) in the forespore and sigma(E) and sigma(K) in the mother cell
      governs compartment-specific gene expression. In this work, we combined genome
      wide transcriptional analyses and promoter mapping to define the C. difficile
      sigma(F), sigma(E), sigma(G) and sigma(K) regulons. We identified about 225 genes
      under the control of these sigma factors: 25 in the sigma(F) regulon, 97 sigma(E)
      dependent genes, 50 sigma(G)-governed genes and 56 genes under sigma(K) control.
      A significant fraction of genes in each regulon is of unknown function but new
      candidates for spore coat proteins could be proposed as being synthesized under
      sigma(E) or sigma(K) control and detected in a previously published spore
      proteome. SpoIIID of C. difficile also plays a pivotal role in the mother cell
      line of expression repressing the transcription of many members of the sigma(E)
      regulon and activating sigK expression. Global analysis of developmental gene
      expression under the control of these sigma factors revealed deviations from the
      B. subtilis model regarding the communication between mother cell and forespore
      in C. difficile. We showed that the expression of the sigma(E) regulon in the
      mother cell was not strictly under the control of sigma(F) despite the fact that
      the forespore product SpoIIR was required for the processing of pro-sigma(E). In
      addition, the sigma(K) regulon was not controlled by sigma(G) in C. difficile in
      agreement with the lack of pro-sigma(K) processing. This work is one key step to
      obtain new insights about the diversity and evolution of the sporulation process
      among Firmicutes. 

PMID- 24098138
TI  - Integrated enrichment analysis of variants and pathways in genome-wide
      association studies indicates central role for IL-2 signaling genes in type 1
      diabetes, and cytokine signaling genes in Crohn's disease.
AB  - Pathway analyses of genome-wide association studies aggregate information over
      sets of related genes, such as genes in common pathways, to identify gene sets
      that are enriched for variants associated with disease. We develop a model-based
      approach to pathway analysis, and apply this approach to data from the Wellcome
      Trust Case Control Consortium (WTCCC) studies. Our method offers several benefits
      over existing approaches. First, our method not only interrogates pathways for
      enrichment of disease associations, but also estimates the level of enrichment,
      which yields a coherent way to promote variants in enriched pathways, enhancing
      discovery of genes underlying disease. Second, our approach allows for multiple
      enriched pathways, a feature that leads to novel findings in two diseases where
      the major histocompatibility complex (MHC) is a major determinant of disease
      susceptibility. Third, by modeling disease as the combined effect of multiple
      markers, our method automatically accounts for linkage disequilibrium among
      variants. Interrogation of pathways from eight pathway databases yields strong
      support for enriched pathways, indicating links between Crohn's disease (CD) and
      cytokine-driven networks that modulate immune responses; between rheumatoid
      arthritis (RA) and "Measles" pathway genes involved in immune responses triggered
      by measles infection; and between type 1 diabetes (T1D) and IL2-mediated
      signaling genes. Prioritizing variants in these enriched pathways yields many
      additional putative disease associations compared to analyses without enrichment.
      For CD and RA, 7 of 8 additional non-MHC associations are corroborated by other
      studies, providing validation for our approach. For T1D, prioritization of IL-2
      signaling genes yields strong evidence for 7 additional non-MHC candidate disease
      loci, as well as suggestive evidence for several more. Of the 7 strongest
      associations, 4 are validated by other studies, and 3 (near IL-2 signaling genes
      RAF1, MAPK14, and FYN) constitute novel putative T1D loci for further study. 

PMID- 24098139
TI  - The spore differentiation pathway in the enteric pathogen Clostridium difficile.
AB  - Endosporulation is an ancient bacterial developmental program that culminates
      with the differentiation of a highly resistant endospore. In the model organism
      Bacillus subtilis, gene expression in the forespore and in the mother cell, the
      two cells that participate in endospore development, is governed by cell type
      specific RNA polymerase sigma subunits. sigma(F) in the forespore, and sigma(E)
      in the mother cell control early stages of development and are replaced, at later
      stages, by sigma(G) and sigma(K), respectively. Starting with sigma(F), the
      activation of the sigma factors is sequential, requires the preceding factor, and
      involves cell-cell signaling pathways that operate at key morphological stages.
      Here, we have studied the function and regulation of the sporulation sigma
      factors in the intestinal pathogen Clostridium difficile, an obligate anaerobe in
      which the endospores are central to the infectious cycle. The morphological
      characterization of mutants for the sporulation sigma factors, in parallel with
      use of a fluorescence reporter for single cell analysis of gene expression,
      unraveled important deviations from the B. subtilis paradigm. While the main
      periods of activity of the sigma factors are conserved, we show that the activity
      of sigma(E) is partially independent of sigma(F), that sigma(G) activity is not
      dependent on sigma(E), and that the activity of sigma(K) does not require
      sigma(G). We also show that sigma(K) is not strictly required for heat resistant
      spore formation. In all, our results indicate reduced temporal segregation
      between the activities of the early and late sigma factors, and reduced
      requirement for the sigma(F)-to-sigma(E), sigma(E)-to-sigma(G), and sigma(G)-to
      sigma(K) cell-cell signaling pathways. Nevertheless, our results support the view
      that the top level of the endosporulation network is conserved in evolution, with
      the sigma factors acting as the key regulators of the pathway, established some
      2.5 billion years ago upon its emergence at the base of the Firmicutes Phylum. 

PMID- 24098140
TI  - Identification of 526 conserved metazoan genetic innovations exposes a new role
      for cofactor E-like in neuronal microtubule homeostasis.
AB  - The evolution of metazoans from their choanoflagellate-like unicellular ancestor
      coincided with the acquisition of novel biological functions to support a
      multicellular lifestyle, and eventually, the unique cellular and physiological
      demands of differentiated cell types such as those forming the nervous, muscle
      and immune systems. In an effort to understand the molecular underpinnings of
      such metazoan innovations, we carried out a comparative genomics analysis for
      genes found exclusively in, and widely conserved across, metazoans. Using this
      approach, we identified a set of 526 core metazoan-specific genes (the
      'metazoanome'), approximately 10% of which are largely uncharacterized, 16% of
      which are associated with known human disease, and 66% of which are conserved in
      Trichoplax adhaerens, a basal metazoan lacking neurons and other specialized cell
      types. Global analyses of previously-characterized core metazoan genes suggest a
      prevalent property, namely that they act as partially redundant modifiers of
      ancient eukaryotic pathways. Our data also highlights the importance of
      exaptation of pre-existing genetic tools during metazoan evolution. Expression
      studies in C. elegans revealed that many metazoan-specific genes, including
      tubulin folding cofactor E-like (TBCEL/coel-1), are expressed in neurons. We used
      C. elegans COEL-1 as a representative to experimentally validate the metazoan
      specific character of our dataset. We show that coel-1 disruption results in
      developmental hypersensitivity to the microtubule drug paclitaxel/taxol, and that
      overexpression of coel-1 has broad effects during embryonic development and
      perturbs specialized microtubules in the touch receptor neurons (TRNs). In
      addition, coel-1 influences the migration, neurite outgrowth and mechanosensory
      function of the TRNs, and functionally interacts with components of the tubulin
      acetylation/deacetylation pathway. Together, our findings unveil a conserved
      molecular toolbox fundamental to metazoan biology that contains a number of
      neuronally expressed and disease-related genes, and reveal a key role for
      TBCEL/coel-1 in regulating microtubule function during metazoan development and
      neuronal differentiation. 

PMID- 24098141
TI  - Distinct regulatory mechanisms act to establish and maintain Pax3 expression in
      the developing neural tube.
AB  - Pattern formation in developing tissues is driven by the interaction of extrinsic
      signals with intrinsic transcriptional networks that together establish spatially
      and temporally restricted profiles of gene expression. How this process is
      orchestrated at the molecular level by genomic cis-regulatory modules is one of
      the central questions in developmental biology. Here we have addressed this by
      analysing the regulation of Pax3 expression in the context of the developing
      spinal cord. Pax3 is induced early during neural development in progenitors of
      the dorsal spinal cord and is maintained as pattern is subsequently elaborated,
      resulting in the segregation of the tissue into dorsal and ventral subdivisions.
      We used a combination of comparative genomics and transgenic assays to define and
      dissect several functional cis-regulatory modules associated with the Pax3 locus.
      We provide evidence that the coordinated activity of two modules establishes and
      refines Pax3 expression during neural tube development. Mutational analyses of
      the initiating element revealed that in addition to Wnt signaling, Nkx family
      homeodomain repressors restrict Pax3 transcription to the presumptive dorsal
      neural tube. Subsequently, a second module mediates direct positive
      autoregulation and feedback to maintain Pax3 expression. Together, these data
      indicate a mechanism by which transient external signals are converted into a
      sustained expression domain by the activities of distinct regulatory elements.
      This transcriptional logic differs from the cross-repression that is responsible
      for the spatiotemporal patterns of gene expression in the ventral neural tube,
      suggesting that a variety of circuits are deployed within the neural tube
      regulatory network to establish and elaborate pattern formation. 

PMID- 24098142
TI  - Multiple signaling pathways coordinate to induce a threshold response in a
      chordate embryo.
AB  - In animal development, secreted signaling molecules evoke all-or-none threshold
      responses of target gene transcription to specify cell fates. In the chordate
      Ciona intestinalis, the neural markers Otx and Nodal are induced at early
      embryonic stages by Fgf9/16/20 signaling. Here we show that three additional
      signaling molecules act negatively to generate a sharp expression boundary for
      neural genes. EphrinA signaling antagonizes FGF signaling by inhibiting ERK
      phosphorylation more strongly in epidermal cells than in neural cells, which
      accentuates differences in the strength of ERK activation. However, even weakly
      activated ERK activates Otx and Nodal transcription occasionally, probably
      because of the inherently stochastic nature of signal transduction processes and
      binding of transcription factors to target sequences. This occasional and
      undesirable activation of neural genes by weak residual ERK activity is directly
      repressed by Smad transcription factors activated by Admp and Gdf1/3-like
      signaling, further sharpening the differential responses of cells to FGF
      signaling. Thus, these signaling pathways coordinate to evoke a threshold
      response that delineates a sharp expression boundary. 

PMID- 24098143
TI  - Both rare and de novo copy number variants are prevalent in agenesis of the
      corpus callosum but not in cerebellar hypoplasia or polymicrogyria.
AB  - Agenesis of the corpus callosum (ACC), cerebellar hypoplasia (CBLH), and
      polymicrogyria (PMG) are severe congenital brain malformations with largely
      undiscovered causes. We conducted a large-scale chromosomal copy number variation
      (CNV) discovery effort in 255 ACC, 220 CBLH, and 147 PMG patients, and 2,349
      controls. Compared to controls, significantly more ACC, but unexpectedly not CBLH
      or PMG patients, had rare genic CNVs over one megabase (p = 1.48*10-3; odds ratio
      [OR] = 3.19; 95% confidence interval [CI] = 1.89-5.39). Rare genic CNVs were
      those that impacted at least one gene in less than 1% of the combined population
      of patients and controls. Compared to controls, significantly more ACC but not
      CBLH or PMG patients had rare CNVs impacting over 20 genes (p = 0.01; OR = 2.95;
      95% CI = 1.69-5.18). Independent qPCR confirmation showed that 9.4% of ACC
      patients had de novo CNVs. These, in comparison to inherited CNVs, preferentially
      overlapped de novo CNVs previously observed in patients with autism spectrum
      disorders (p = 3.06*10-4; OR = 7.55; 95% CI = 2.40-23.72). Interestingly,
      numerous reports have shown a reduced corpus callosum area in autistic patients,
      and diminished social and executive function in many ACC patients. We also
      confirmed and refined previously known CNVs, including significantly narrowing
      the 8p23.1-p11.1 duplication present in 2% of our current ACC cohort. We found
      six novel CNVs, each in a single patient, that are likely deleterious: deletions
      of 1p31.3-p31.1, 1q31.2-q31.3, 5q23.1, and 15q11.2-q13.1; and duplications of
      2q11.2-q13 and 11p14.3-p14.2. One ACC patient with microcephaly had a paternally
      inherited deletion of 16p13.11 that included NDE1. Exome sequencing identified a
      recessive maternally inherited nonsense mutation in the non-deleted allele of
      NDE1, revealing the complexity of ACC genetics. This is the first systematic
      study of CNVs in congenital brain malformations, and shows a much higher
      prevalence of large gene-rich CNVs in ACC than in CBLH and PMG.

PMID- 24098144
TI  - Direct monitoring of the strand passage reaction of DNA topoisomerase II triggers
      checkpoint activation.
AB  - By necessity, the ancient activity of type II topoisomerases co-evolved with the
      double-helical structure of DNA, at least in organisms with circular genomes. In
      humans, the strand passage reaction of DNA topoisomerase II (Topo II) is the
      target of several major classes of cancer drugs which both poison Topo II and
      activate cell cycle checkpoint controls. It is important to know the cellular
      effects of molecules that target Topo II, but the mechanisms of checkpoint
      activation that respond to Topo II dysfunction are not well understood. Here, we
      provide evidence that a checkpoint mechanism monitors the strand passage reaction
      of Topo II. In contrast, cells do not become checkpoint arrested in the presence
      of the aberrant DNA topologies, such as hyper-catenation, that arise in the
      absence of Topo II activity. An overall reduction in Topo II activity (i.e. slow
      strand passage cycles) does not activate the checkpoint, but specific defects in
      the T-segment transit step of the strand passage reaction do induce a cell cycle
      delay. Furthermore, the cell cycle delay depends on the divergent and
      catalytically inert C-terminal region of Topo II, indicating that transmission of
      a checkpoint signal may occur via the C-terminus. Other, well characterized,
      mitotic checkpoints detect DNA lesions or monitor unattached kinetochores; these
      defects arise via failures in a variety of cell processes. In contrast, we have
      described the first example of a distinct category of checkpoint mechanism that
      monitors the catalytic cycle of a single specific enzyme in order to determine
      when chromosome segregation can proceed faithfully. 

PMID- 24098145
TI  - The serum resistome of a globally disseminated multidrug resistant uropathogenic
      Escherichia coli clone.
AB  - Escherichia coli ST131 is a globally disseminated, multidrug resistant clone
      responsible for a high proportion of urinary tract and bloodstream infections.
      The rapid emergence and successful spread of E. coli ST131 is strongly associated
      with antibiotic resistance; however, this phenotype alone is unlikely to explain
      its dominance amongst multidrug resistant uropathogens circulating worldwide in
      hospitals and the community. Thus, a greater understanding of the molecular
      mechanisms that underpin the fitness of E. coli ST131 is required. In this study,
      we employed hyper-saturated transposon mutagenesis in combination with
      multiplexed transposon directed insertion-site sequencing to define the essential
      genes required for in vitro growth and the serum resistome (i.e. genes required
      for resistance to human serum) of E. coli EC958, a representative of the
      predominant E. coli ST131 clonal lineage. We identified 315 essential genes in E.
      coli EC958, 231 (73%) of which were also essential in E. coli K-12. The serum
      resistome comprised 56 genes, the majority of which encode membrane proteins or
      factors involved in lipopolysaccharide (LPS) biosynthesis. Targeted mutagenesis
      confirmed a role in serum resistance for 46 (82%) of these genes. The murein
      lipoprotein Lpp, along with two lipid A-core biosynthesis enzymes WaaP and WaaG,
      were most strongly associated with serum resistance. While LPS was the main
      resistance mechanism defined for E. coli EC958 in serum, the enterobacterial
      common antigen and colanic acid also impacted on this phenotype. Our analysis
      also identified a novel function for two genes, hyxA and hyxR, as minor
      regulators of O-antigen chain length. This study offers novel insight into the
      genetic make-up of E. coli ST131, and provides a framework for future research on
      E. coli and other Gram-negative pathogens to define their essential gene
      repertoire and to dissect the molecular mechanisms that enable them to survive in
      the bloodstream and cause disease. 

PMID- 24098146
TI  - SUMO localizes to the central element of synaptonemal complex and is required for
      the full synapsis of meiotic chromosomes in budding yeast.
AB  - The synaptonemal complex (SC) is a widely conserved structure that mediates the
      intimate alignment of homologous chromosomes during meiotic prophase and is
      required for proper homolog segregation at meiosis I. However, fundamental
      details of SC architecture and assembly remain poorly understood. The coiled-coil
      protein, Zip1, is the only component whose arrangement within the mature SC of
      budding yeast has been extensively characterized. It has been proposed that the
      Small Ubiquitin-like MOdifier, SUMO, plays a role in SC assembly by linking
      chromosome axes with Zip1's C termini. The role of SUMO in SC structure has not
      been directly tested, however, because cells lacking SUMO are inviable. Here, we
      provide direct evidence for SUMO's function in SC assembly. A meiotic smt3
      reduction-of-function strain displays reduced sporulation, abnormal levels of
      crossover recombination, and diminished SC assembly. SC structures are nearly
      absent when induced at later meiotic time points in the smt3 reduction-of
      function background. Using Structured Illumination Microscopy we furthermore
      determine the position of SUMO within budding yeast SC structure. In contrast to
      previous models that positioned SUMO near Zip1's C termini, we demonstrate that
      SUMO lies at the midline of SC central region proximal to Zip1's N termini,
      within a subdomain called the "central element". The recently identified
      SUMOylated SC component, Ecm11, also localizes to the SC central element.
      Finally, we show that SUMO, Ecm11, and even unSUMOylatable Ecm11 exhibit Zip1
      like ongoing incorporation into previously established SCs during meiotic
      prophase and that the relative abundance of SUMO and Ecm11 correlates with Zip1's
      abundance within SCs of varying Zip1 content. We discuss a model in which central
      element proteins are core building blocks that stabilize the architecture of SC
      near Zip1's N termini, and where SUMOylation may occur subsequent to the
      incorporation of components like Ecm11 into an SC precursor structure. 

PMID- 24098147
TI  - Incorporating motif analysis into gene co-expression networks reveals novel
      modular expression pattern and new signaling pathways.
AB  - Understanding of gene regulatory networks requires discovery of expression
      modules within gene co-expression networks and identification of promoter motifs
      and corresponding transcription factors that regulate their expression. A
      commonly used method for this purpose is a top-down approach based on clustering
      the network into a range of densely connected segments, treating these segments
      as expression modules, and extracting promoter motifs from these modules. Here,
      we describe a novel bottom-up approach to identify gene expression modules driven
      by known cis-regulatory motifs in the gene promoters. For a specific motif, genes
      in the co-expression network are ranked according to their probability of
      belonging to an expression module regulated by that motif. The ranking is
      conducted via motif enrichment or motif position bias analysis. Our results
      indicate that motif position bias analysis is an effective tool for genome-wide
      motif analysis. Sub-networks containing the top ranked genes are extracted and
      analyzed for inherent gene expression modules. This approach identified novel
      expression modules for the G-box, W-box, site II, and MYB motifs from an
      Arabidopsis thaliana gene co-expression network based on the graphical Gaussian
      model. The novel expression modules include those involved in house-keeping
      functions, primary and secondary metabolism, and abiotic and biotic stress
      responses. In addition to confirmation of previously described modules, we
      identified modules that include new signaling pathways. To associate
      transcription factors that regulate genes in these co-expression modules, we
      developed a novel reporter system. Using this approach, we evaluated MYB
      transcription factor-promoter interactions within MYB motif modules. 

PMID- 24098148
TI  - Coordinate regulation of mature dopaminergic axon morphology by macroautophagy
      and the PTEN signaling pathway.
AB  - Macroautophagy is a conserved mechanism for the bulk degradation of proteins and
      organelles. Pathological studies have implicated defective macroautophagy in
      neurodegeneration, but physiological functions of macroautophagy in adult neurons
      remain unclear. Here we show that Atg7, an essential macroautophagy component,
      regulates dopaminergic axon terminal morphology. Mature Atg7-deficient midbrain
      dopamine (DA) neurons harbored selectively enlarged axonal terminals. This
      contrasted with the phenotype of DA neurons deficient in Pten - a key negative
      regulator of the mTOR kinase signaling pathway and neuron size - that displayed
      enlarged soma but unaltered axon terminals. Surprisingly, concomitant deficiency
      of both Atg7 and Pten led to a dramatic enhancement of axon terminal enlargement
      relative to Atg7 deletion alone. Similar genetic interactions between Atg7 and
      Pten were observed in the context of DA turnover and DA-dependent locomotor
      behaviors. These data suggest a model for morphological regulation of mature
      dopaminergic axon terminals whereby the impact of mTOR pathway is suppressed by
      macroautophagy. 

PMID- 24098150
TI  - A mutation in the SUV39H2 gene in Labrador Retrievers with hereditary nasal
      parakeratosis (HNPK) provides insights into the epigenetics of keratinocyte
      differentiation.
AB  - Hereditary nasal parakeratosis (HNPK), an inherited monogenic autosomal recessive
      skin disorder, leads to crusts and fissures on the nasal planum of Labrador
      Retrievers. We performed a genome-wide association study (GWAS) using 13 HNPK
      cases and 23 controls. We obtained a single strong association signal on
      chromosome 2 (p(raw) = 4.4*10-14). The analysis of shared haplotypes among the 13
      cases defined a critical interval of 1.6 Mb with 25 predicted genes. We re
      sequenced the genome of one case at 38* coverage and detected 3 non-synonymous
      variants in the critical interval with respect to the reference genome assembly.
      We genotyped these variants in larger cohorts of dogs and only one was perfectly
      associated with the HNPK phenotype in a cohort of more than 500 dogs. This
      candidate causative variant is a missense variant in the SUV39H2 gene encoding a
      histone 3 lysine 9 (H3K9) methyltransferase, which mediates chromatin silencing.
      The variant c.972T>G is predicted to change an evolutionary conserved asparagine
      into a lysine in the catalytically active domain of the enzyme (p.N324K). We
      further studied the histopathological alterations in the epidermis in vivo. Our
      data suggest that the HNPK phenotype is not caused by hyperproliferation, but
      rather delayed terminal differentiation of keratinocytes. Thus, our data provide
      evidence that SUV39H2 is involved in the epigenetic regulation of keratinocyte
      differentiation ensuring proper stratification and tight sealing of the mammalian
      epidermis.

PMID- 24098149
TI  - A GDF5 point mutation strikes twice--causing BDA1 and SYNS2.
AB  - Growth and Differentiation Factor 5 (GDF5) is a secreted growth factor that
      belongs to the Bone Morphogenetic Protein (BMP) family and plays a pivotal role
      during limb development. GDF5 is a susceptibility gene for osteoarthritis (OA)
      and mutations in GDF5 are associated with a wide variety of skeletal
      malformations ranging from complex syndromes such as acromesomelic
      chondrodysplasias to isolated forms of brachydactylies or multiple synostoses
      syndrome 2 (SYNS2). Here, we report on a family with an autosomal dominant
      inherited combination of SYNS2 and additional brachydactyly type A1 (BDA1) caused
      by a single point mutation in GDF5 (p.W414R). Functional studies, including
      chondrogenesis assays with primary mesenchymal cells, luciferase reporter gene
      assays and Surface Plasmon Resonance analysis, of the GDF5(W414R) variant in
      comparison to other GDF5 mutations associated with isolated BDA1 (p.R399C) or
      SYNS2 (p.E491K) revealed a dual pathomechanism characterized by a gain- and loss
      of-function at the same time. On the one hand insensitivity to the main GDF5
      antagonist NOGGIN (NOG) leads to a GDF5 gain of function and subsequent SYNS2
      phenotype. Whereas on the other hand, a reduced signaling activity, specifically
      via the BMP receptor type IA (BMPR1A), is likely responsible for the BDA1
      phenotype. These results demonstrate that one mutation in the overlapping
      interface of antagonist and receptor binding site in GDF5 can lead to a GDF5
      variant with pathophysiological relevance for both, BDA1 and SYNS2 development.
      Consequently, our study assembles another part of the molecular puzzle of how
      loss and gain of function mutations in GDF5 affect bone development in hands and
      feet resulting in specific types of brachydactyly and SYNS2. These novel insights
      into the biology of GDF5 might also provide further clues on the pathophysiology
      of OA.

PMID- 24098151
TI  - A genetic RNAi screen for IP3/Ca2+ coupled GPCRs in Drosophila identifies the
      PdfR as a regulator of insect flight.
AB  - Insect flight is regulated by various sensory inputs and neuromodulatory circuits
      which function in synchrony to control and fine-tune the final behavioral
      outcome. The cellular and molecular bases of flight neuromodulatory circuits are
      not well defined. In Drosophila melanogaster, it is known that neuronal IP3
      receptor mediated Ca2+ signaling and store-operated Ca2+ entry (SOCE) are
      required for air-puff stimulated adult flight. However, G-protein coupled
      receptors (GPCRs) that activate intracellular Ca2+ signaling in the context of
      flight are unknown in Drosophila. We performed a genetic RNAi screen to identify
      GPCRs that regulate flight by activating the IPIP3 receptor. Among the 108 GPCRs
      screened, we discovered 5 IPIP3/Ca2+ linked GPCRs that are necessary for
      maintenance of air-puff stimulated flight. Analysis of their temporal requirement
      established that while some GPCRs are required only during flight circuit
      development, others are required both in pupal development as well as during
      adult flight. Interestingly, our study identified the Pigment Dispersing Factor
      Receptor (PdfR) as a regulator of flight circuit development and as a modulator
      of acute flight. From the analysis of PdfR expressing neurons relevant for flight
      and its well-defined roles in other behavioral paradigms, we propose that PdfR
      signaling functions systemically to integrate multiple sensory inputs and
      modulate downstream motor behavior.

PMID- 24098152
TI  - Evolutionary change within a bipotential switch shaped the sperm/oocyte decision
      in hermaphroditic nematodes.
AB  - A subset of transcription factors like Gli2 and Oct1 are bipotential--they can
      activate or repress the same target, in response to changing signals from
      upstream genes. Some previous studies implied that the sex-determination protein
      TRA-1 might also be bipotential; here we confirm this hypothesis by identifying a
      co-factor, and use it to explore how the structure of a bipotential switch
      changes during evolution. First, null mutants reveal that C. briggsae TRR-1 is
      required for spermatogenesis, RNA interference implies that it works as part of
      the Tip60 Histone Acetyl Transferase complex, and RT-PCR data show that it
      promotes the expression of Cbr-fog-3, a gene needed for spermatogenesis. Second,
      epistasis tests reveal that TRR-1 works through TRA-1, both to activate Cbr-fog-3
      and to control the sperm/oocyte decision. Since previous studies showed that TRA
      1 can repress fog-3 as well, these observations demonstrate that it is
      bipotential. Third, TRR-1 also regulates the development of the male tail. Since
      Cbr-tra-2 Cbr-trr-1 double mutants resemble Cbr-tra-1 null mutants, these two
      regulatory branches control all tra-1 activity. Fourth, striking differences in
      the relationship between these two branches of the switch have arisen during
      recent evolution. C. briggsae trr-1 null mutants prevent hermaphrodite
      spermatogenesis, but not Cbr-fem null mutants, which disrupt the other half of
      the switch. On the other hand, C. elegans fem null mutants prevent
      spermatogenesis, but not Cel-trr-1 mutants. However, synthetic interactions
      confirm that both halves of the switch exist in each species. Thus, the
      relationship between the two halves of a bipotential switch can shift rapidly
      during evolution, so that the same phenotype is produce by alternative,
      complementary mechanisms.

PMID- 24098153
TI  - Genetic architecture of skewed X inactivation in the laboratory mouse.
AB  - X chromosome inactivation (XCI) is the mammalian mechanism of dosage compensation
      that balances X-linked gene expression between the sexes. Early during female
      development, each cell of the embryo proper independently inactivates one of its
      two parental X-chromosomes. In mice, the choice of which X chromosome is
      inactivated is affected by the genotype of a cis-acting locus, the X-chromosome
      controlling element (Xce). Xce has been localized to a 1.9 Mb interval within the
      X-inactivation center (Xic), yet its molecular identity and mechanism of action
      remain unknown. We combined genotype and sequence data for mouse stocks with
      detailed phenotyping of ten inbred strains and with the development of a
      statistical model that incorporates phenotyping data from multiple sources to
      disentangle sources of XCI phenotypic variance in natural female populations on X
      inactivation. We have reduced the Xce candidate 10-fold to a 176 kb region
      located approximately 500 kb proximal to Xist. We propose that structural
      variation in this interval explains the presence of multiple functional Xce
      alleles in the genus Mus. We have identified a new allele, Xce(e) present in Mus
      musculus and a possible sixth functional allele in Mus spicilegus. We have also
      confirmed a parent-of-origin effect on X inactivation choice and provide evidence
      that maternal inheritance magnifies the skewing associated with strong Xce
      alleles. Based on the phylogenetic analysis of 155 laboratory strains and wild
      mice we conclude that Xce(a) is either a derived allele that arose concurrently
      with the domestication of fancy mice but prior the derivation of most classical
      inbred strains or a rare allele in the wild. Furthermore, we have found that
      despite the presence of multiple haplotypes in the wild Mus musculus domesticus
      has only one functional Xce allele, Xce(b). Lastly, we conclude that each mouse
      taxa examined has a different functional Xce allele.

PMID- 24098156
TI  - Redetermination of tamarugite, NaAl(SO4)2.6H2O.
AB  - The crystal structure of tamarugite [sodium aluminium bis-(sulfate) hexa-hydrate]
      was redetermined from a single crystal from Mina Alcaparossa, near Cerritos
      Bayos, southwest of Calama, Chile. In contrast to the previous work [Robinson &
      Fang (1969 ?). Am. Mineral. 54, 19-30], all non-H atoms were refined with
      anisotropic displacement parameters and H-atoms were located by difference
      Fourier methods and refined from X-ray diffraction data. The structure is built
      up from nearly regular [Al(H2O)6](3+) octa-hedra and infinite double-stranded
      chains [Na(SO4)2](3-) that extend parallel to [001]. The Na(+) cation has a
      strongly distorted octa-hedral coordination by sulfate O atoms [Na-O = 2.2709
      (11) - 2.5117 (12) A], of which five are furnished by the chain-building sulfate
      group S2O4 and one by the non-bridging sulfate group S1O4. The [Na(SO4)2](3-)
      chain features an unusual centrosymmetric group formed by two NaO6 octa-hedra and
      two S2O4 tetra-hedra sharing five adjacent edges, one between two NaO6 octa-hedra
      and two each between the resulting double octa-hedron and two S2O4 tetra-hedra.
      These groups are then linked into a double-stranded chain via corner-sharing
      between NaO6 octa-hedra and S2O4 tetra-hedra. The S1O4 group, attached to Na in
      the terminal position, completes the chains. The [Al(H2O)6](3+) octa-hedron (<Al
      O> = 1.885 (11) A) donates 12 comparatively strong hydrogen bonds (O?O = 2.6665
      (14) - 2.7971 (15) A) to the sulfate O atoms of three neighbouring [Na(SO4)2](3-)
      chains, helping to connect them in three dimensions, but with a prevalence
      parallel to (010), the cleavage plane of the mineral. Compared with the previous
      work on tamarugite, the bond precision of Al-O bond lengths as an example
      improved from 0.024 to 0.001 A. 

PMID- 24098155
TI  - Sugammadex as a reversal agent for neuromuscular block: an evidence-based review.
AB  - Sugammadex is the first clinical representative of a new class of drugs called
      selective relaxant binding agents. It has revolutionized the way
      anesthesiologists think about drug reversal. Sugammadex selectively binds
      rocuronium or vecuronium, thereby reversing their neuromuscular blocking action.
      Due to its 1:1 binding of rocuronium or vecuronium, it is able to reverse any
      depth of neuromuscular block. So far, it has been approved for use in adult
      patients and for pediatric patients over 2 years. Since its approval in Europe,
      Japan, and Australia, further insight on its use in special patient populations
      and specific diseases have become available. Due to its pharmacodynamic profile,
      sugammadex, in combination with rocuronium, may have the potential to displace
      succinylcholine as the "gold standard" muscle relaxant for rapid sequence
      induction. The use of rocuronium or vecuronium, with the potential of reverse of
      their action with sugammadex, seems to be safe in patients with impaired
      neuromuscular transmission, ie, neuromuscular diseases, including myasthenia
      gravis. Data from long-term use of sugammadex is not yet available. Evidence
      suggesting an economic advantage of using sugammadex and justifying its
      relatively high cost for an anesthesia-related drug, is missing. 

PMID- 24098157
TI  - beta-Xenophyllite-type Na4Li0.62Co5.67Al0.71(AsO4)6.
AB  - The title compound, tetrasodium lithium cobalt aluminium hexa-(orthoarsenate),
      was synthesized by a solid state reaction route. In the crystal structure, Co(2+)
      ions are partially substituted by Al(3+) in an octa-hedral environment [M1 with
      site symmetry 2/m; occupancy ratio Co:Al = 0.286 (10):0.714 (10)]. The charge
      compensation is ensured by Li(+) cations sharing a tetra-hedral site with Co(2+)
      ions [M2 with site symmetry 2; occupancy ratio Co:Li = 0.690 (5):0.310 (5)]. The
      anionic unit is formed by two octa-hedra and three tetra-hedra linked only by
      corners. The CoM1M2As2O19 units associate to an open three-dimensional framework
      containing tunnels propagating along the a-axis direction. One Na(+) cation is
      located in the periphery of the tunnels while the other two are situated in the
      centres: all Na(+) cations exhibit half-occupancy. The structure of the studied
      material is compared with those of various related minerals reported in the
      literature. 

PMID- 24098154
TI  - Stimulation of mTORC1 with L-leucine rescues defects associated with Roberts
      syndrome.
AB  - Roberts syndrome (RBS) is a human disease characterized by defects in limb and
      craniofacial development and growth and mental retardation. RBS is caused by
      mutations in ESCO2, a gene which encodes an acetyltransferase for the cohesin
      complex. While the essential role of the cohesin complex in chromosome
      segregation has been well characterized, it plays additional roles in DNA damage
      repair, chromosome condensation, and gene expression. The developmental
      phenotypes of Roberts syndrome and other cohesinopathies suggest that gene
      expression is impaired during embryogenesis. It was previously reported that
      ribosomal RNA production and protein translation were impaired in immortalized
      RBS cells. It was speculated that cohesin binding at the rDNA was important for
      nucleolar form and function. We have explored the hypothesis that reduced
      ribosome function contributes to RBS in zebrafish models and human cells. Two key
      pathways that sense cellular stress are the p53 and mTOR pathways. We report that
      mTOR signaling is inhibited in human RBS cells based on the reduced
      phosphorylation of the downstream effectors S6K1, S6 and 4EBP1, and this
      correlates with p53 activation. Nucleoli, the sites of ribosome production, are
      highly fragmented in RBS cells. We tested the effect of inhibiting p53 or
      stimulating mTOR in RBS cells. The rescue provided by mTOR activation was more
      significant, with activation rescuing both cell division and cell death. To study
      this cohesinopathy in a whole animal model we used ESCO2-mutant and morphant
      zebrafish embryos, which have developmental defects mimicking RBS. Consistent
      with RBS patient cells, the ESCO2 mutant embryos show p53 activation and
      inhibition of the TOR pathway. Stimulation of the TOR pathway with L-leucine
      rescued many developmental defects of ESCO2-mutant embryos. Our data support the
      idea that RBS can be attributed in part to defects in ribosome biogenesis, and
      stimulation of the TOR pathway has therapeutic potential. 

PMID- 24098158
TI  - Na3.88Mo15Se19: a novel ternary reduced molybdenum selenide containing Mo6 and
      Mo9 clusters.
AB  - The structure of tetrasodium penta-deca-molybdenum nona-deca-selenide,
      Na3.88Mo15Se19, is isotypic with the In3+x Mo15Se19 compounds [Gruttner et al.
      (1979 ?). Acta Cryst. B35, 285-292]. It is characterized by two cluster units,
      Mo6Se (i) 8Se (a) 6 and Mo9Se (i) 11Se (a) 6 (where i represents inner and a
      apical atoms), that are present in a 1:1 ratio. The cluster units are centered at
      Wyckoff positions 2b and 2c and have point-group symmetry -3 and -6,
      respectively. The clusters are inter-connected through additional Mo-Se bonds. In
      the title compound, the Na(+) cations replace the trivalent as well as the
      monovalent indium atoms present in In3.9Mo15Se19. One Mo, one Se and one Na atom
      are situated on mirror planes, and two other Se atoms and one Na atom [occupancy
      0.628 (14)] are situated on threefold rotation axes. The crystal studied was
      twinned by merohedry with refined components of 0.4216 (12) and 0.5784 (12). 

PMID- 24098160
TI  - Tetra-yttrium difluoride disilicate orthosilicate, Y4F2[Si2O7][SiO4].
AB  - In the crystal structure of Y4F2[Si2O7][SiO4], three fundamental building blocks
      are present, viz. anionic disilicate and orthosilicate units ([Si2O7](6-) and
      [SiO4](4-)) and cationic [F2Y4](10+) entities. The latter are built up by two
      [FY3](8+) triangles sharing a common edge. The four crystallographically
      independent Y(3+) cations display coordination numbers of eight for one and of
      seven for the other three cations, provided by oxide and fluoride anions. The
      overall arrangement of the building blocks can be considered as layer-like
      parallel to the ac plane. 

PMID- 24098159
TI  - SBN60, strontium-barium niobate at 100 K.
AB  - The title compound, Sr0.6Ba0.4Nb2O6 (strontium barium niobium oxide), belongs to
      the group of strontium-barium niobates with varying composition of Sr and Ba.
      Their general formula can be written as Sr x Ba1 - x Nb2O6. Below the Curie
      temperature, T c , these materials indicate ferroelectric properties. The Curie
      temperature for SBN60 is equal to 346+/-0.5 K so the structure is in the
      ferroelectric phase at the measurement temperature of 100 K. Characteristic for
      this family of compounds is the packing along the z-axis. The NbO6 corner-sharing
      octa-hedra surround three types of vacancy tunnels with penta-gonal, square and
      triangular shapes. The Sr(2+) ions partially occupy two unique sites, the first
      one located inside the penta-gon and the second one in the square tunnels.
      Consequently, they are situated on the mirror plane and the inter-section of two
      glide planes, respectively. The site inside the penta-gonal tunnel is
      additionally disordered so that the same position is shared by Ba(2+) and Sr(2+)
      ions whereas another part of the Ba(2+) ion occupies a different position
      (relative occupancies 0.43:0.41:0.16). One of the Nb(V) atoms and three of the
      O(2-) ions occupy general positions. The second Nb(V) atom is located on the
      inter-section of the mirror planes. Two remaining O(2-) ions are located on the
      same mirror plane. Only the Nb(V) atom and one of the O(2-) ions which is located
      on the mirror plane are not disordered. Each of the remaining O(2-) ions is split
      between two sites, with relative occupancies of 0.52:0.48 (O(2-) ions in general
      positions) and 0.64:0.36 (O(2-) ion on the mirror plane). 

PMID- 24098161
TI  - The monoclinic form of trilithium dichromium(III) tris-(orthophosphate).
AB  - The monoclinic form of trilithium dichromium(III) tris-(ortho-phosphate),
      Li3Cr2(PO4)3, was prepared by the reactive halide flux method. The structure of
      the title compound is composed of a three-dimensional anionic framework with
      composition infinity (3)[Cr2(PO4)3](3-) and Li(+) ions situated in the empty
      channels. The rigid framework built up from CrO6 octa-hedra and PO4 tetra-hedra
      is the same as that found in other monoclinic Li3 M 2(PO4)3 (M = Fe, Sc, V)
      phases. The three Li(+) cations of Li3Cr2(PO4)3 are unequally disordered over six
      crystallographically different sites. The classical charge balance of the title
      compound can be represented as [Li(+)]3[Cr(3+)]2[P(5+)]3[O(2-)]12. Solid-state
      UV/Vis spectra indicate that the crystal filed splitting (Delta0) of the Cr(3+)
      ion is around 2.22 eV. 

PMID- 24098162
TI  - Bis[MU-1-(3,5-di-chloro-pyridin-2-yl)-2-(pyridin-3-yl-methyl-idene)hydrazine]bis
      [(nitrato-kappaO)silver(I)] aceto-nitrile disolvate.
AB  - In the centrosymmetric binuclear title complex, [Ag2(NO3)2(C11H8Cl2N4)2].2CH3CN,
      the Ag(I) atom is four-coordinated and exhibits a highly distorted tetrahedral
      coordination sphere defined by three N atoms from two 1-(3,5-di-chloro-pyridin-2
      yl)-2-(pyridin-3-yl-methyl-idene)hy-drazine ligands and one O atom from a nitrate
      anion. Inter-molecular N-H?O hydrogen bonds link the complex mol-ecules,
      resulting in a two-dimensional supra-molecular structure parallel to (001). 

PMID- 24098163
TI  - Tri-carbonyl-chlorido-(6',7'-di-hydro-5'H-spiro-[cyclo-pentane-1,6'-dipyrido[3,2
      d:2',3'-f][1,3]diazepine]-kappa(2) N (1),N (11))rhenium(I).
AB  - In the title compound, [ReCl(C15H16N4)(CO)3], the Re(I) ion is coordinated in a
      distorted octa-hedral geometry by one Cl atom, two N atoms of the bidentate
      ligand and three carbonyl groups. The cyclo-pentane group is orientated in a
      transoid fashion with respect to the chloride ligand. The dihedral angle between
      the pryridine rings is 10.91 (12) degrees . In the crystal, N-H?Cl hydrogen bonds
      link complex mol-ecules, forming a two-dimensional network parallel to (001). 

PMID- 24098164
TI  - Tri-carbonyl-chlorido-(6',7'-di-hydro-5'H-spiro-[cyclo-hexane-1,6'-dipyrido[3,2
      d:2',3'-f][1,3]diazepine]-kappa(2) N (1),N (11))rhenium(I).
AB  - In the title compound, [ReCl(C16H18N4)(CO)3], the Re(I) ion is coordinated in a
      distorted octa-hedral geometry by one Cl atom, two N atoms of the bidentate
      ligand and three carbonyl groups. The cyclo-hexane group is orientated in a
      transoid fashion with respect to the chloride ligand. In the crystal, N-H?Cl
      hydrogen bonds link complex mol-ecules, forming a two-dimensional network
      parallel to (100). 

PMID- 24098165
TI  - {2-[1-(2-Meth-oxy-6-oxidophenyl-kappaO (6))ethyl-idene]-N-methyl-hydrazinecarbo
      thio-amidato-kappa(2) N (2),S}(tri-phenyl-phosphane-kappaP)palladium(II) ethanol
      monosolvate.
AB  - In the title compound, [Pd(C11H13N3O2S)(C18H15P)].C2H5OH, the Pd(II) atom is
      tetra-coordinated in a slightly distorted square-planar environment by three
      donor atoms (NOS) from a thio-semicarbazonate ligand, forming five- and six
      membered chelate rings, and a P atom from a neutral tri-phenyl-phosphane group.
      The five-membered ring adopts a distorted envelope conformation with Pd(II) as
      the flap atom, while the six-membered ring forms a slightly twisted screw-boat
      conformation. A slightly distorted screw-boat form of a meth-oxy-phenyl group is
      fused to the six-membered ring. Weak C-H?O inter-actions form dimers in the
      asymmetric unit and along [001] which help to stabilize the crystal packing. 

PMID- 24098166
TI  - (2,3,5,6-Tetra-fluoro-phenolato)[5,10,15,20-tetra-kis-(4-meth-oxy-phen
      yl)porphyrinato]iron(III) cyclo-hexane monosolvate.
AB  - The title compound, [Fe(C6HF4O)(C48H36N4O4)].C6H12, represents a five-coordinate
      iron(III) porphyrin complex in a square-pyramidal geometry with a tetra-fluoro
      phenolate anion as the axial ligand. The Fe(III) atom is displaced by 0.364 (2) A
      from the 24-atom mean plane of the porphyrinate ring towards the tetra-fluoro
      phenolate anion. The average Fe-N distance is 2.053 (2) A and the Fe-O distance
      is 1.883 (2) A. A porphyrin aryl H atom points in the general direction of the
      phenoxide ring. The mean plane separation between the 24-atom porphyrin planes of
      two adjacent porphyrin rings is ~3.7 A, and the lateral shift is ~3.5 A resu,
      ting in an Fe?Fe separation of 5.6167 (14) A. 

PMID- 24098167
TI  - Bis[1-meth-oxy-2,2,2-tris-(pyrazol-1-yl-kappaN (2))ethane]-nickel(II) bis-(tri
      fluoro-methane-sulfonate) dihydrate.
AB  - In the title salt, [Ni(C12H14N6O)2](CF3SO3)2.2H2O, the Ni(II) cation is located
      on an inversion centre and is coordinated by six N atoms from two tridentate 1
      meth-oxy-2,2,2-tris-(pyrazol-1-yl)ethane ligands in a distorted octa-hedral
      geometry. The Ni-N distances range from 2.0594 (12) to 2.0664 (12) A, intra
      ligand N-Ni-N angles range from 84.59 (5) to 86.06 (5) degrees , and adjacent
      inter-ligand N-Ni-N angles range between 93.94 (5) and 95.41 (5) degrees . In the
      crystal, inversion-related pyrazole rings are pi-pi stacked, with an inter-planar
      spacing of 3.4494 (18) A, forming chains that propagate parallel to the a-axis
      direction. Inter-molecular O-H?O hydrogen bonds are present between water mol
      ecules and tri-fluoro-methane-sulfonate anions. 

PMID- 24098168
TI  - [MU-3,3'-Bis(tri-hydro-bor-yl)[3]ferroceno-phane]bis-(chlorido-zirconocene).
AB  - The title compound, [FeZr2(C5H5)4Cl2(C13H18B2)], is a heteronuclear complex that
      consists of a [3]ferrocenophane moiety substituted at each cyclo-penta-dienyl
      (Cp) ring by a BH3 group; the BH3 group is bonded via two H atoms to the Zr atom
      of the zirconocene chloride moiety in a bidentate fashion. The two Cp rings of
      the [3]ferrocenophane moiety are aligned at a dihedral angle of 8.9 (4) degrees 
      arising from the strain of the propane-1,3-diyl bridge linking the two Cp rings.
      [One methyl-ene group is disordered over two positions with a site-occupation
      factor of 0.552 (18) for the major occupied site.] The dihedral angles between
      the Cp rings at the two Zr atoms are 50.0 (3) and 51.7 (3) degrees . The bonding
      Zr?H distances are in the range 1.89 (7)-2.14 (7) A. As the two Cp rings of the
      ferrocene unit are connected by an ansa bridge, the two Zr atoms approach each
      other at 6.485 (1) A. The crystal packing features C-H?Cl inter-actions. 

PMID- 24098169
TI  - Di-bromido-bis-(2-methyl-1H-benzimidazole-kappaN (3))cadmium.
AB  - In the title compound, [CdBr2(C8H8N2)2], the Cd(II) atom has a distorted tetra
      hedral coordination formed by the two imino N atoms of two 2-methyl-benzimidazole
      ligands and two terminal bromide ligands. The Cd(II) atom is slightly out of the
      benzimidazole planes by 0.320 (3) and 0.210 (3) A. The dihedral angle between the
      benzimidazole planes is 71.6 (2) degrees . In the crystal, mol-ecules are linked
      by N-H?Br hydrogen bonds into puckered layers parallel to (001). 

PMID- 24098170
TI  - Bis[1-meth-oxy-2,2,2-tris-(pyrazol-1-yl-kappaN (2))ethane]-nickel(II) bis-(tri
      fluoro-methane-sulfonate) methanol disolvate.
AB  - In the title salt, [Ni(C12H14N6O)2](CF3SO3)2.2CH3OH, the Ni(II) ion is
      coordinated by six N atoms from two tridentate 1-meth-oxy-2,2,2-tris-(pyrazol-1
      yl)ethane ligands in a distorted octa-hedral geometry. The Ni(II) ion is situated
      on an inversion centre. The Ni-N distances range from 2.0589 (19) to 2.0757 (19)
      A, intra-ligand N-Ni-N angles range from 84.50 (8) to 85.15 (8) degrees , and
      adjacent inter-ligand N-Ni-N angles range between 94.85 (8) and 95.50 (8) degrees
      . In the crystal, O-H?O hydrogen bonds between methanol solvent mol-ecules and
      tri-fluoro-methane-sulfonate anions are observed. 

PMID- 24098171
TI  - catena-Poly[[tri-aqua-copper(II)]-MU-5-carb-oxy-benzene-1,3-di-carboxyl-ato
      kappa(2) O (1):O (3)].
AB  - In the title complex, [Cu(C9H4O6)(H2O)3] n , the Cu(II) cation exhibits a
      distorted square-pyramidal coordination geometry involving five O atoms from two
      monodentate 5-carb-oxy-benzene-1,3-di-carboxyl-ate anions and three water mol
      ecules. The 5-carb-oxy-benzene-1,3-di-carboxyl-ate anions bridge Cu(II) cations
      into zigzag polymeric chains running along the b-axis direction. These chains are
      further linked by O-H?O hydrogen bonds between coordinating water mol-ecules or
      carboxyl groups and carboxylate groups into a three-dimensional supra-molecular
      architecture. In the crystal, pi-pi stacking is observed between parallel benzene
      rings of adjacent chains, the centroid-centroid distances being 3.584 (3) and
      3.684 (3) A. 

PMID- 24098172
TI  - Di-chlorido-diphenyl-bis-(thio-urea-kappaS)tin(IV).
AB  - The title compound, [Sn(C6H5)2Cl2(CH4N2S)2], has been obtained from the reaction
      between Sn(C6H5)2Cl2 and SC(NH2)2. The asymmetric unit consists of one half of
      the mol-ecular unit, the remainder generated by a twofold rotation axis located
      along the Cl-Sn-Cl bonds. The Sn(IV) atom is coordinated by two phenyl groups,
      two Cl atoms and two thio-urea ligands in an all trans octa-hedral C2Cl2S2
      environment. Individual mol-ecules are connected through N-H?Cl hydrogen bonds,
      leading to a three-dimensional network structure. Intra-molecular N-H?Cl hydrogen
      bonds are also present. 

PMID- 24098173
TI  - Poly[tetra-methyl-ammonium [tri-MU2-formato-kappa(6) O:O'-manganate(II)]].
AB  - In the title compound, {(C4H12N)[Mn(HCO2)3]} n , the Mn(II) atom lies on an
      inversion centre and is coordinated by O-atom donors from the three double
      bridging formate ligands, one of which lies across a crystallographic mirror
      plane, giving a slightly distorted octahedral coordination sphere. A three
      dimensional NaCl-type framework is generated in which the tetra-methyl-ammonium
      cations, which lie across mirror planes and occupy the cavities in the polymer
      structure, form weak C-H?O hydrogen bonds with the formate ligands. 

PMID- 24098174
TI  - MU-(2,6-Bis{[3-(di-methyl-amino)-prop-yl]imino-meth-yl}-4-methyl-phenolato)-MU
      hydroxido-bis-[(thio-cyanato-kappaN)copper(II)].
AB  - In the title compound, [Cu2(C19H31N4O)(OH)(NCS)2], the mol-ecular structure of
      the dinuclear complex reveals two penta-coordinated Cu(II) ions, which are
      bridged by the phenolate O atom of the ligand and by an exogenous hydroxide ion.
      The bridging atoms occupy equatorial positions in the coordination sphere of the
      metal atoms and complete the equatorial coordination planes with two ligand N
      atoms, the apical positions being occupied by thio-cyanate N atoms. The crystal
      structure also features pi-pi stacking inter-actions involving the benzene rings
      with a centroid-centroid distance of 3.764 (4)A. The crystal studied was a non
      merohedral twin, with a refined BASF value of 0.203 (2). 

PMID- 24098175
TI  - Tetra-kis(aceto-nitrile)copper(I) hydrogen oxalate-oxalic acid-aceto-nitrile
      (1/0.5/0.5).
AB  - In the title compound, [Cu(CH3CN)4](C2HO4).0.5C2H2O4.0.5CH3CN, the Cu(I) ion is
      coordinated by the N atoms of four aceto-nitrile ligands in a slightly distorted
      tetra-hedral environment. The oxalic acid mol-ecule lies across an inversion
      center. The aceto-nitrile solvent mol-ecule is disordered across an inversion
      center and was refined with half occupancy. In the crystal, the hydrogen oxalate
      anions and oxalic acid mol-ecules are linked via O-H?O hydrogen bonds, forming
      chains along [010]. 

PMID- 24098176
TI  - m-Xylylenediaminium di-aqua-bis-[di-hydrogen diphosphato(2-)]cobaltate(II)
      dihydrate.
AB  - In the title complex, (C8H14N2)[Co(H2P2O7)2(H2O)2].2H2O, the Co(II) ion lies on
      an inversion center and is coordinated by two bidentate diphosphate ligands and
      two water mol-ecules in a slightly distorted octa-hedral coordination geometry.
      The m-xylylenediaminium cation is located on a twofold rotation axis. In the
      crystal, a three-dimensional supra-molecular assembly is constructed by O-H?O and
      N-H?O hydrogen bonds between the organic cations, complex anions and uncoordin
      ated water mol-ecules. 

PMID- 24098177
TI  - Bis-(eta(2)-ethyl-ene)(eta(5)-inden-yl)iridium(I).
AB  - The asymmetric unit of the title compound, [Ir(C9H7)(C2H4)2], consists of two
      independent mol-ecules. The bonding between iridium and the five-membered ring of
      the indenyl ligand shows the usual asymmetry associated with the typical ring
      slippage responsible for the enhanced activity of indenyl metal compounds when
      compared with the analogous cyclo-penta-dienyl metal compound. There are three
      short Ir-C bonds of 2.210 (3), 2.190 (4) and 2.220 (3) A and two long Ir-C bonds
      to the C atoms that are part of the fused six-membered ring of 2.349 (4) and
      2.366 (3) A for one of the independent mol-ecules [2.208 (4), 2.222 (3), 2.197
      (4) A for the short distances and 2.371 (3) and 2.358 (3) A for the long
      distances in the second mol-ecule]. This results in both indenyl ligands being
      slightly kinked, with dihedral angles of 6.8 (4) degrees  and 6.5 (4) degrees . 

PMID- 24098178
TI  - Bis((E)-2-{3-[4-(1H-imidazol-1-yl-kappaN (3))styr-yl]-5,5-di-methyl-cyclo-hex-2
      enyl-idene}malono-nitrile)-diiodido-mercury(II).
AB  - In the title compound, [HgI2(C22H20N4)2], the Hg(II) cation is situated on a
      twofold rotation axis and is coordinated by two iodide anions and two imidazolyl
      N atoms in a distorted tetra-hedral geometry. In the crystal, C-H?I inter-actions
      link the mol-ecules into chains extending in [010], which are further linked into
      sheets parallel to (100) through C-H?N hydrogen bonding inter-actions. 

PMID- 24098179
TI  - Tris-[4-(di-methyl-amino)-pyridine][tris(pyra-zol-1-yl)methane]--ruthenium(II)
      bis-(hexa-fluorido-phosphate) diethyl ether monosolvate.
AB  - In the title compound, [Ru(C10H10N6)(C7H10N2)3](PF6)2.C4H10O, the Ru(II) cation
      is coordinated by one tris-(1-pyrazol-yl)methane (Tpm) and three
      dimethylaminopyridine (dmap) ligands in a slightly distorted octa-hedral
      geometry. The asymmetric unit consists of one complex cation, two hexa-fluorido
      phosphate anions and one diethyl ether solvent mol-ecule in general positions.
      Although quite a large number of ruthenium complexes of the facially coordinating
      tridentate Tpm ligand have been structurally characterized, this is only the
      second one containing three pyridyl co-ligands. The average Ru-N(Tpm) distance is
      2.059 (12) A, while the average Ru-N(dmap) [dmap = 4-(di-methyl-amino)-pyridine]
      distance is somewhat longer at 2.108 (13) A. The orientation of the dmap ligands
      varies greatly, with dihedral angles between the pyridyl and opposite pyrazolyl
      rings of 14.3 (2), 23.2 (2) and 61.2 (2) degrees . 

PMID- 24098180
TI  - Bis{MU-2-meth-oxy-6-[(methyl-imino)-meth-yl]phenolato}bis-({2-meth-oxy-6-[(methyl
      imino)-meth-yl]phenolato}copper(II)).
AB  - The title compound, [Cu2(C9H10NO2)4], is built of discrete centrosymmetric
      dimers. The Cu(II) atoms are each five coordinated by two deprotonated Schiff
      base ligands that are bonded differently to the metal atoms. Of the two phenolate
      O atoms, one is coordinated to one Cu(II) atom, whereas another bridges the two
      metal atoms. The basal plane of the square pyramid around Cu(II) atoms is formed
      by the imino N and phenolate O atoms of the bidentate and the
      monodentate/bidentate Schiff base ligands. The bridging phenolate oxygen occupies
      the apical position of the coordination sphere with a considerably longer Cu-O
      bond length. In the crystal, the dimeric mol-ecules pack relative to each other
      in such a way that the Cu2O2 planes of adjacent dimers are orthogonal. 

PMID- 24098181
TI  - {9-Hexyl-2-[2-phenyl-6-(pyridin-2-yl)pyridin-4-yl]-9H-carbazole}di-iodido-zinc.
AB  - In the title compound, [ZnI2(C34H31N3)], the Zn(II) atom is four-coordinated by
      two I atoms and the pyridine N atoms from the bidentate 6'-phenyl-2,2'-bi
      pyridine ligand in a distorted tetra-hedral geometry. 

PMID- 24098182
TI  - Di-MU-methanolato-bis[(2-tert-butyl-6-methylphenolato-kappaO)methyl
      titanium(IV)].
AB  - The molecule of the title compound, [Ti2(CH3)2(CH3O)2(C11H15O)4] or {[Ti(Me)(MU
      OCH3)(OC6H3CMe3-2-Me-6)]2}, has a centrosymmetric, dimeric structure with a
      distorted square pyramidal array about each titanium atom. The methoxide ligands
      form an asymmetric bridge between the two Ti(IV) atoms [Ti-O bond lengths of
      1.9794 (12) and 2.0603 (12) A] with the two phenolato ligands occupying the
      remaining basal sites [Ti-O 1.8218 (11) and 1.8135 (11) A]. The Ti-O-C phenolato
      bond angles are similar at 161.24 (10) and 160.66 (11) degrees . The methyl
      ligand attached to the metal atom has a Ti-C bond length of 2.0878 (17) A. 

PMID- 24098183
TI  - Bis((E)-2-{5,5-di-methyl-3-[4-(1H-1,2,4-triazol-1-yl-kappaN (4))styr-yl]cyclo-hex
      2-enyl-idene}malono-nitrile)-diiodido-mercury(II).
AB  - In the title complex, [HgI2(C21H19N5)2], the Hg(II) ion is located on a twofold
      rotation axis and is coordinated by two I atoms and two N atoms from two (E)-2
      {5,5-di-methyl-3-[4-(1H-1,2,4-triazol-1-yl)styr-yl]cyclo-hex-2-enyl-idene}malono
      nitrile ligands in a distorted tetra-hedral geometry. In the crystal, the mol
      ecules are linked by inter-molecular pi-pi inter-actions between the triazole and
      benzene rings [centroid-centroid distance = 3.794 (3) A] into a band extending in
      [010]. These bands are further connected by C-H?N hydrogen bonds into a two
      dimensional network parallel to (100). 

PMID- 24098184
TI  - Poly[MU5-(4-meth-oxy-benzene-sulfonato)-sodium].
AB  - In the title complex, [Na(C7H7O4S)] n , the Na(I) ion is coord-inated in a
      slightly distorted penta-gonal-bipyramidal environment by seven O atoms [Na-O =
      2.3198 (16)-2.5585 (17) A]. The 4-methoxybenzenesulfonate anions act as bis
      chelating and bridging ligands, forming a two-dimensional polymer parallel to
      (001), which is further linked into a three-dimensional network by weak C-H?O
      hydrogen bonds. 

PMID- 24098185
TI  - {5,5'-Dihydroxy-2,2'-[(2-hydroxypropane-1,3-diyl)bis(nitrilomethanylyli
      dene)]diphenolato}nickel(II) dihydrate.
AB  - In the title complex, [Ni(C17H16N2O5)].2H2O, the Ni(II) ion is four-coordinated
      by two azomethine N and two phenolato O atoms of the tetradentate Schiff base
      ligand in a slightly distorted square-planar geometry. In the six-membered ring
      containing the metal, the azomethine N atoms and the three C atoms of the
      connecting 1,3-di-amino-propane-2-ol, all atoms except the metal are disordered
      over two sets of sites with an occupacy ratio of 0.566 (3):0.434 (3). The central
      C atom of the major component is significantly out of the mean plane of the
      remaing atoms while the conformation of this ring in the minor component is
      noticeably different. In the crystal, O-H?O hydrogen bonds involving the lattice
      water mol-ecules and the hy-droxy groups are observed. 

PMID- 24098186
TI  - Bis(1,10-phenanthroline-kappa(2) N,N')(sulfato-kappaO)zinc(II) propane-1,2-diol
      monosolvate.
AB  - In the title compound, [Zn(SO4)(C12H8N2)2].C3H8O2, the Zn(II) ion is in a
      distorted square-pyramidal coordination environment composed of four N atoms from
      two chelating 1,10-phenanthroline ligands and one O atom from a monodentate
      sulfate ligand. The Zn(II) ion lies on a twofold rotation axis. The sulfate
      ligand and propane-1,2-diol mol-ecules are disordered across the twofold rotation
      axis. The dihedral angle between the two chelating N2C2 groups is 83.26 (13)
      degrees . In the crystal, the complex mol-ecule and the propane-1,2-diol mol
      ecule are connected through a pair of O-H?O hydrogen bonds. 

PMID- 24098187
TI  - Tetra-butyl-ammonium butyl-tetra-chlorido-stannate(IV).
AB  - In the title compound, [N(C4H9)4][Sn(C4H9)Cl4], the Sn(IV) atom of the stannate
      anion has a trigonal-bipyramidal coordination sphere by two Cl atoms and one
      butyl chain in the equatorial plane and by two Cl atoms in the apical positions.
      Two of the four butyl chains of the tetra-butyl-ammonium cation are partially
      disordered, each with refined site occupancies of 0.691 (6):0.309 (6). Weak C
      H?Cl hydrogen-bonding inter-actions help to consolidate the crystal packing, as
      well as a short Cl?Cl inter-action of 3.295 (2) A. 

PMID- 24098188
TI  - (2,3,5,6-Tetra-fluoro-phenolato-kappaO)(5,10,15,20-tetra-phenyl
      porphyrinato)iron(III).
AB  - The title compound, [Fe(C44H28N4)(C6HF4O)], is a porphyrin complex with iron(III)
      in fivefold coordination with a tetra-fluoro-phenolate group as the axial ligand.
      The Fe atom and the phenolate ligand are disordered across the porphyrin ring
      with the two phenolates appearing to be roughly related by a center of symmetry.
      The occupancies of the two phenolate groups refined to 0.788 (3) for the major
      component and 0.212 (3) for the minor component. The structure shows
      extraordinary Fe displacements of 0.488 (4) (major) and 0.673 (4) A (minor) from
      the 24-atom mean plane of the porphyrin. The Fe-Np distances range from 2.063 (4)
      to 2.187 (6) A and the Fe-O distances are 1.903 (5) A for major component and
      1.87 (2) A for minor component. The four phenyl groups attached to the porphyrin
      ring form dihedral angles of 63.4 (4), 49.6 (4), 62.4 (4), and 63.3 (4) degrees 
      (in increasing numerical order) with the three nearest C atoms of the porphyrin
      ring. The major and minor component phenolate groups form dihedral angles of 24.9
      (4) degrees  and 24.8 (4) degrees , respectively, with the four porphyrin N
      atoms. The Fe?Fe distance between the two iron(III) atoms of adjacent porphyrin
      mol-ecules is 6.677 (3) A. No close inter-molecular inter-action was observed.
      The crystal studied was twinned by inversion, with a major-minor component ratio
      of 0.53 (3):0.47 (3). 

PMID- 24098189
TI  - Azido-(eta(5)-penta-methyl-cyclo-penta-dien-yl)[2-(pyridin-2-yl)phen
      yl]iridium(III).
AB  - In the title compound, [Ir(C10H15)(C11H8N)(N3)], the Ir(III) ion is coordinated
      by three anionic ligands, namely, penta-methyl-cyclo-penta-dienyl (Cp*(-)), 2
      (pyridin-2-yl)phenyl (ppy(-)) and azide (N3 (-)), and adopts a three-legged piano
      stool geometry The coordination mode of N3 (-) is typical for Cp*Ir(III)-N3
      complexes, with an Ir-N(N3) bond length of 2.125 (2) A and an Ir-N=N bond angle
      of 116.5 (2) degrees . The N3 (-) ligand is almost linear [N=N=N = 176.0 (3)
      degrees ], and the N=N bond length between the central and coordinating N atom
      and that between the central and non-coordinating terminal N atom are 1.194 (3)
      and 1.157 (3) A, respectively. For the ppy(-) ligand, the Ir-C and Ir-N bond
      lengths are 2.066 (3) and 2.079 (3) A, respectively, which are rather close to
      each other, compared to the related Ir(III)- or Rh(III)-ppy complexes. The Ir
      C(Cp*) bond lengths vary in the range 2.163 (2)-2.232 (2) A, indicating a strong
      trans influence of the cyclo-metallated C-donor atom of the ppy(-) ligand. 

PMID- 24098190
TI  - Pyridinium trans-di-aqua-bis-[oxalato(2-)-kappa(2) O (1),O (2)]chromate(III) urea
      monosolvate.
AB  - The asymmetric unit of the title solvated mol-ecular salt,
      (C5H6N)[Cr(C2O4)2(H2O)2].CO(NH2)2, contains half a formula unit. Each component
      is completed by crystallographic twofold symmetry: in the cation, one C and the N
      atom lie on the rotation axis; in the anion, the Cr(III) ion lies on the axis; in
      the solvent mol-ecule, the C and the O atom lie on the axis. The aqua ligands are
      in a trans disposition in the resulting CrO6 octa-hedron. In the crystal, the
      components are linked by O-H?O, N-H?O and N-H?(O,O) hydrogen bonds, generating a
      three-dimensional network. 

PMID- 24098191
TI  - Bis(1,10-phenanthroline-kappa(2) N,N')(sulfato-kappaO)copper(II) ethanol
      monosolvate.
AB  - The crystal structure of the title compound, [Cu(SO4)(C12H8N2)2].C2H5OH, arises
      from the assembly of the neutral complex [Cu(SO4)(C12H8N2)2] and an ethanol
      solvent mol-ecule. The Cu(II) ion is five-coordinate, surrounded by two pairs of
      N atoms from two independent N,N'-chelating 1,10-phenanthroline ligands, and one
      O atom of monodentate sulfate ligand, in a distorted trigonal-bipyramidal
      fashion. Spatial orientation of the ligands and the assembly in the solid state
      are stabilized by the C-H?O hydrogen-bonding inter-actions, established between
      the O atoms (from the sulfate ligand and the ethanol mol-ecule) and the
      neighbouring 1,10-phenanthroline mol-ecules. There is also an offset face-to-face
      pi-pi stacking between the 1,10-phenanthroline ligands. The ethanol solvent mol
      ecule is disordered over two orientations in the ratio 0.663 (10):0.337 (10). The
      crystal examined was subject to racemic twinning and the refined twin fraction
      was 0.346 (19). 

PMID- 24098192
TI  - (3S,3aS,6R,6aR)-2-Oxohexa-hydro-furo[3,2-b]furan-3,6-diyl dibenzoate.
AB  - The title compound, C20H16O7, contains a cis-fused gamma-lactone tetra-hydro
      furan ring system functionalized with two benzo-yloxy groups. Both rings adopt an
      envelope conformation. The mol-ecule assumes an elongated shape and exibits non
      crystallographic C 2 symmetry. The benzo-yloxy groups are almost planar [maximum
      deviations of 0.0491 (15) and 0.0336 (17) A for the O atoms] and their mean
      planes are inclined to one another by 16.51 (4) degrees . The crystal packing
      features weak C-H?O inter-actions. The aryl groups of adjacent mol-ecules are
      parallel shifted with face-to-face contacts and a shortest inter-molecular C?C
      distance of 3.482 (4) A. 

PMID- 24098193
TI  - 4,6-Di-bromo-N-{3-[(4,6-di-bromo-2,3-di-methyl-phenyl)imino]butan-2-yl-idene}-2,3
      di-methyl-aniline.
AB  - The title compound, C20H20Br4N2, is a product of the condensation reaction of 4,6
      di-bromo-2,3-di-methyl-aniline and butane-2,3-dione. The mol-ecule has a center
      of symmetry at the mid-point of the central C-C bond. The dihedral angle between
      the benzene ring and the 1,4-di-aza-butadiene plane is 78.3 (2) degrees . Niether
      hydrogen bonding nor aromatic stacking is observed in the crystal structure. 

PMID- 24098194
TI  - N-p-Tolyl-1,3-selenazolo[5,4-b]pyridin-2-amine.
AB  - In the title compound, C13H11N3Se, the dihedral angle between the mean plane of
      the fused seleno-azolo-pyridine ring system and the p-toluidine ring is 14.260
      (5) degrees . In the crystal, mol-ecules are linked by N-H?N hydrogen bonds,
      forming zigzag chains extending along the b-axis direction. 

PMID- 24098195
TI  - (E)-1-(3-Formyl-phen-yl)-2-(2-oxidonaphthalen-1-yl)diazen-1-ium.
AB  - In the title zwitterion, C17H12N2O2, the dihedral angle between the benzene ring
      and naphthalene ring system is 11.76 (7) degrees  and an intra-molecular N-H?O
      hydrogen bond exists. In the crystal, molecules are linked via pairs of C-H?O
      hydrogen bonds, forming inversion dimers. 

PMID- 24098196
TI  - 1-(4-{[(1,3,3-Tri-methyl-indolin-2-yl-idene)meth-yl]diazen-yl}phen-yl)ethanone.
AB  - The title compound, C20H21N3O, has crystallographic mirror symmetry with all non
      H atoms apart from the methyl C atom of the CMe2 group lying on the mirror plane.
      Mol-ecules are linked into planar sheets parallel to (010) by phen-yl-azo C-H?N
      and phen-yl-ethanone C-H?O inter-actions. Methyl C-H?pi inter-actions provide
      crosslinking between the planes. 

PMID- 24098197
TI  - 6-Meth-oxy-4-(2,4,5-tri-meth-oxy-phen-yl)-2,2'-bi-pyridine-5-carbo-nitrile.
AB  - In the title 3-cyano-pyridine derivative, C21H19N3O4, the 3-cyano-substituted
      pyridine ring forms dihedral angles of 2.35 (5) and 41.60 (5) degrees  with the
      unsubstituted pyridine and 2,4,5-trimeth-oxy-substituted benzene rings,
      respectively. The dihedral angle between the unsubstituted pyridine and benzene
      rings is 39.84 (5) degrees . The meth-oxy groups form Cmeth-yl-O-C-(C,N) torsion
      angles in the range 0.80 (15)-11.45 (15) degrees . In the crystal, mol-ecules
      related by 21 screw axes are linked by weak C-H?N hydrogen bonds along [010]. In
      addition, weak C-H?pi inter-actions and pi-pi stacking inter-actions between
      pyridine rings, with a centroid-centroid distance of 3.6448 (6) A, are observed. 

PMID- 24098198
TI  - 1-(3,5-Di-meth-oxy-phen-yl)-4,5-dimethyl-2-phenyl-1H-imidazole.
AB  - In the title mol-ecule, C19H20N2O2, the imidazole ring makes dihedral angles of
      57.29 (5) and 31.54 (5) degrees  with the attached di-meth-oxy-phenyl residue and
      the phenyl ring, respectively. The dihedral angle between the di-meth-oxy-phenyl
      and phenyl rings is 61.15 (5) degrees . In the crystal, pairs of C-H?N hydrogen
      bonds connect the mol-ecules into inversion dimers. 

PMID- 24098199
TI  - 1-(3-Carboxyl-atophen-yl)-4,4'-bipyridin-1-ium dihydrate.
AB  - In the crystal structure of the title compound, C17H12N2O2.2H2O, the carboxyl-ate
      group is linked via O-H?O hydrogen bonds to two water mol-ecules. The crystal
      packing is best described as parallel layers (viewed along the a axis) of
      viologen and water mol-ecules associated via O-H?O hydrogen bonds and pi-pi inter
      actions, with a centroid-centroid separation of 3.8276 (9) A. 

PMID- 24098200
TI  - (2R*,4R*,7S*,10R*,12R*)-3,11,13,15-Tetra-oxa-penta-cyclo
      [5.5.3.0(1,7).0(2,4).0(10,12)]penta-deca-5,8-dien-14-one.
AB  - The title compound, C11H8O5, features a 'skipped' diene, an anti-bis-(epoxide)
      and a cyclic carbonate, all embedded in a densely functionalized
      [4.4.3]propellane scaffold. The crystal packing of this diepoxide is effected
      primarily by C-H?O hydrogen bonds, which link the mol-ecules into tapes along the
      b axis. Inter-tape connectivity is brought about by centrosymmetrically disposed
      pairs of C?O contacts [3.183 (4) A] between the C(delta+)=O(delta-) dipoles of
      neighbouring carbonate moieties. 

PMID- 24098201
TI  - The co-crystal N,N'-bis-[(pyridin-1-ium-2-yl)meth-yl]ethane-dithio-amide bis-(2,6
      di-nitro-benzoate)-2,6-di-nitro-benzoic acid (1/4).
AB  - The asymmetric unit of title co-crystal, C14H16N4S2 (2+).2C7H3N2O6 (-).4C7H4N2O6,
      comprises a centrosymmetric dipyridinium dication, a 2,6-di-nitro-benzoate anion
      and two independent 2,6-di-nitro-benzoic acid mol-ecules. The pyridin-ium rings
      are each approximately perpendicular to the central di-thio-amide unit [dihedral
      angle = 80.67 (12) degrees ]. The carboxyl-ate/carb-oxy-lic acid groups are
      approximately perpendicular to the benzene ring to which they are attached
      [dihedral angles = 78.85 (16), 81.46 (19) and 71.28 (15) degrees ]. By contrast,
      the major twist exhibited by a nitro group is manifested in a dihedral angle of
      32.66 (17) degrees . The most prominent feature of the crystal packing is linear
      supra-molecular chains along [1-10], featuring O-H?O(carboxyl-ate) and pyridinium
      N-H?O hydrogen bonds. These are consolidated into a three-dimensional
      architecture by thio-amide-nitro N-H?O, C-H?O and pi-pi [inter-centroid distance
      = 3.524 (2) A] inter-actions. One of the nitro O atoms was refined over two
      sites; the major site was 0.65 (7) occupied. 

PMID- 24098202
TI  - 1,5-Bis(4-chloro-phen-yl)-3-(4-methyl-phen-yl)pentane-1,5-dione.
AB  - In the title mol-ecule, C24H20Cl2O2, the central methyl-benzene ring forms
      dihedral angles of 42.47 (10) and 34.34 (10) degrees  with the terminal 4-chloro
      phenyl fragments. The dihedral angle between the chloro-benzene rings is 34.45
      (11) degrees . A weak intra-molecular C-H?O inter-action generates an S(6) ring
      motif. The crystal packing exhibits weak C-H?O hydrogen bonds and C-H?pi inter
      actions. 

PMID- 24098203
TI  - (E)-2-[4-(Di-ethyl-amino)-styr-yl]-1-methyl-quinolinium 4-fluoro-benzene
      sulfonate monohydrate.
AB  - In the title hydrated molecular salt, C22H25N2 (+).C6H4FO3S(-).H2O, the cation
      displays whole mol-ecule disorder over two sets of sites in a 0.780 (5):0.220 (5)
      ratio. The quinolinium ring system is essentially planar, with r.m.s. deviations
      of 0.0162 and 0.0381 A for the major and minor disorder components, respectively.
      The dihedral angles between the mean plane of the quinolinium ring system and the
      benzene ring are 5.1 (3) and 7.7 (11) degrees , respectively, for the major and
      minor components in the cation. In the crystal, cations, anions and water mol
      ecules are linked into chains along [010] by O-H?O hydrogen bonds and are further
      connected into a three-dimensional network by weak C-H?O and C-H?F inter-actions.
      In addition, pi-pi inter-actions with centroid-centroid distances of 3.634 (3),
      3.702 (5) and 3.838 (5) A are observed. 

PMID- 24098204
TI  - 1,2:5,6-Di-O-iso-propyl-idene-3-C-methyl-alpha-d-allo-furan-ose.
AB  - The title carbohydrate, C13H22O6, is a derivative of d-glycose, in which the
      furan-osidic and iso-propyl-idene rings are in twisted conformations. The mean
      plane of the furan-osidic ring makes a dihedral angle of 70.32 (18) degrees  with
      the mean plane of the fused iso-propyl-idene ring. The methyl groups in the other
      iso-propyl-idene ring are disordered over two sets of sites, with an occupancy
      ratio of 0.74 (6):0.26 (6). In the crystal, mol-ecules are linked by O-H?O
      hydrogen bonds into chains with graph-set notation C(5) along [100]. Weak C-H?O
      interactions also occur. 

PMID- 24098205
TI  - (6,6-Dimethyl-1-phenyl-6,7-di-hydro-5H-pyrrolizin-2-yl)(thio-phen-2-yl)methanone.
AB  - In the title compound, C20H19NOS, the pyrrolizine ring is essentially planar
      (r.m.s. deviation = 0.001 A) while the fused dihydro-pyrrolizine ring adopts an
      envelope comformation with the C atom bearing the methyl substituents as the
      flap. The dihedral angles between the pyrrolizine and the phenyl and thio-phene
      rings are 34.54 (7) and 44.93 (7) degrees , respectively. In the crystal, weak C
      H?O hydrogen bonds link the mol-ecules into infinite zigzag chains parallel to
      the b-axis direction. 

PMID- 24098206
TI  - 3,3''-Bis(9-hy-droxy-fluoren-9-yl)-1,1':3',1''-terphen-yl.
AB  - The asymmetric unit of the title compound, C44H30O2, contains two independent mol
      ecules in which the terminal rings of the terphenyl element are inclined at
      angles of 36.3 (1) and 22.5 (1) degrees  with respect to the central ring and the
      dihedral angles between the fluorenyl units are 72.3 (1) and 62.8 (1) degrees .
      In the crystal, pairs of O-H?O hydrogen bonds link the mol-ecules into inversion
      dimers. The hy-droxy H atoms not involved in these hydrogen bonds form O-H?pi
      inter-actions in which the central terphenyl rings act as acceptors. Weak C-H?O
      contacts and pi-pi [centroid-centroid distance = 4.088 (2) A] stacking inter
      actions also occur. Taking into account directed non-covalent bonding between the
      molecules, the crystal is constructed of supramolecular strands extending along
      the a-axis direction. 

PMID- 24098207
TI  - Dimethyl 3,3'-(phenyl-methyl-ene)bis-(1H-indole-2-carboxyl-ate).
AB  - In the title compound, C27H22N2O4, the two indole ring systems are approximately
      perpendicular to each other, with a dihedral angle of 84.5 (5) degrees  between
      their planes; the benzene ring is twisted with respect to the two indole ring
      systems at angles of 78.5 (5) and 86.5 (3) degrees . In the crystal, mol-ecules
      are linked by N-H?O hydrogen bonds, weak C-H?O and C-H?N hydrogen bonds, and C
      H?pi inter-actions into a three-dimensional supra-molecular architecture. 

PMID- 24098208
TI  - Ethyl 1'-methyl-2-oxo-4'-[(3aR,5R,5aS,8aS,8bR)-2,2,7,7-tetra-methyl-tetra-hydro
      3aH-bis-[1,3]dioxolo[4,5-b:4',5'-d]pyran-5-yl]-2H-spiro-[ace-naphthyl-ene-1,2'
      pyrrolidine]-3'-carboxyl-ate.
AB  - In the title mol-ecule, C30H35NO8, the ace-naphthyl-enone moiety, two atoms of a
      methyl pyrrolidine ring (N and C atoms) and four atoms of an ethyl acetate moiety
      (two C and two O atoms) are disordered over two sets of sites in ratio 0.532
      (7):0.468 (7). The three C atoms of a di-meth-oxy-ethane ring and dioxolane ring
      attached with two methyl groups are disordered over two sets of sites in 0.66
      (2):0.34 (2) and 0.62 (2):0.38 (2) ratios, respectively. The major and minor
      components of the ace-naphthyl-ene ring are essentially planar (r.m.s. deviations
      = 0.0254 and 0.0436 A, respectively). The major and minor components of the
      pyrrolidine ring adopt C-envelope conformations with C atoms displaced by 0.492
      (11) and 0.595 (7) A from the remaining ring atoms. One of the dioxolane rings is
      disordered with its major component in an envelope conformation [C displaced by
      0.511 (11) A] and the minor fraction is more or less planar with an r.m.s.
      deviation of 0.070 A. The other dioxolane ring is in an envelope conformation,
      with a C atom displaced by 0.438 (3) A from the remainder of the ring atoms. The
      crystal packing features C-H?O inter-actions, which generate C(9) chains. 

PMID- 24098209
TI  - 2,3,4,5,6-Penta-fluoro-trans-cinnamic acid.
AB  - The title compound, C9H3F5O2, crystallizes as O-H?O hydrogen-bonded carb-oxy-lic
      acid dimers that, together with C-H?F inter-actions and O?F [2.8065 (13) and
      2.9628 (13) A] and F?F [2.6665 (11), 2.7049 (12) and 2.7314 (12) A] contacts,
      form a sheet-like structure. The sheets are stacked via short pi-pi inter-actions
      [centroid-centroid distance = 4.3198 (11) A]. An intra-molecular C-H?F inter
      action is also observed. 

PMID- 24098210
TI  - 2-(Benzyl-carbamo-yl)nicotinic acid.
AB  - In the title compound, C14H12N2O3, the pyridine ring is twisted with respect to
      the phenyl ring and the carb-oxy-lic acid group at angles of 37.1 (5) and 8.1 (3)
      degrees , respectively; the phenyl ring forms a dihedral angle of 41.4 (1)
      degrees  with the mean plane of the C-NH-C=O fragment. An intra-molecular O-H?O
      hydrogen bond occurs between the carb-oxy-lic acid and carbonyl groups. In the
      crystal, N-H?O hydrogen bonds link mol-ecules into a supra-molecular chain
      running along the a-axis direction. 

PMID- 24098211
TI  - 6-Chloro-3-[(di-methyl-amino)-methyl-idene]thio-chroman-4-one.
AB  - The asymmetric unit of the title compound, C12H12ClNOS, contains three
      independent mol-ecules, with the thio-chroman ring adopting a sofa conformation
      in each one. The crystal structure features C-H?O inter-actions; one of the O
      atoms accepts three such bonds. Together, the hydrogen bonds give rise to a
      molecular tape propagating in [010]. 

PMID- 24098212
TI  - 2-{(E)-[(2Z)-2-(1,2-Di-hydro-phthalazin-1-yl-idene)hydrazinyl-idene]meth
      yl}phenol.
AB  - The title compound, C15H12N4O, adopts an E conformation with respect to the
      azomethine bond and crystallizes in its hydrazinyl-idene tautomeric form. The
      dihedral angle between the ring systems is 15.98 (7) degrees . The phenol O-H
      group forms an intra-molecular O-H?N hydrogen bond. In the crystal, pairs of N
      H?N and C-H?O hydrogen bonds link neighbouring mol-ecules into centrosymmetric
      dimers. These dimers are inter-connected by means of three types of pi-pi
      stacking inter-actions. One, with a centroid-centroid distance of 3.577 (1) A
      [inter-planar separation = 3.4673 (6) A], connects adjacent mol-ecules into
      centrosymmetric dimers. The other two inter-actions, on the outward facing sides
      of the dimers, are between phenol rings of neighboring mol-ecules [centroid
      centroid separation = 3.7907 (13) A and inter-planar separation = 3.5071 (8) A],
      and between phthalazin units [centroid-centroid separation = 3.6001 (12) A and
      inter-planar separation = 3.4891 (7) A]. In combination, the pi-pi inter-actions
      lead to the formation of infinite layers with mol-ecules stacked along [0-11].
      These layers are, in turn, connected with neighbouring layers through the N-H?N
      and C-H?O hydrogen bonds, yielding a three-dimensional supra-molecular
      architecture. 

PMID- 24098213
TI  - N-(2-Fluoro-phen-yl)-2,6-dimethyl-1,3-dioxan-4-amine.
AB  - In the title compound, C12H16FNO3, the dioxane ring adopts a chair conformation
      with the methyl groups and amine N atom in equatorial positions. The best plane
      through the dioxane ring makes a dihedral angle of 43.16 (8) degrees  with the
      phenyl ring. In the crystal, pairs of C-H?O hydrogen bonds link the mol-ecules
      into centrosymmetric R 2 (2)(8) dimers, which are linked into [100] chains by
      further C-H?O hydrogen bonds. The N-H group does not participate in hydrogen
      bonding. 

PMID- 24098214
TI  - 2,4-Bis(4-fluoro-phen-yl)-1,5-dimethyl-3-aza-bicyclo-[3.3.1]nonan-9-one.
AB  - The asymmetric unit of the title compound, C22H23F2NO, contains two independent
      mol-ecules, A and B. The bicyclic system adopts a twin-chair conformation in both
      mol-ecules. The dihedral angles between the fluoro-phenyl rings are 55.27 (8) and
      56.37 (7) degrees  in mol-ecules A and B, respectively. The NH groups are not
      involved in hydrogen bonding due to the steric hindrance of fluoro-phenyl groups.
      The crystal structure features weak C-H?O inter-actions. 

PMID- 24098215
TI  - Dipentyl 2,6-di-amino-benzo[1,2-b:4,5-b']di-furan-3,7-di-carboxyl-ate.
AB  - The title compound, C22H28N2O6, crystallizes with one half-mol-ecule in the
      independent unit, the mol-ecule being located on an inversion centre. The penthyl
      groups are in the all-trans conformation and an almost planar conformation of the
      whole mol-ecule is observed [maximum deviation from the least-squares plane
      through all non-H atoms is 0.0229 (17) A for an N atom]. The amino groups are
      involved in intra- and inter-molecular hydrogen bonds. Intra-molecular hydrogen
      bonding involving the amino group and ester carbonyl helps to lock the syn
      conformation of the ester with respect to the amino group. In the crystal, N-H?O
      hydrogen bonding involving the amino group and the furan and ester carbonyl O
      atoms self-assembles the mol-ecules into a two-dimensional hydrogen-bonded
      network parallel to (010) that displays inter-digital packing sustained by alk-yl
      alkyl inter-actions. 

PMID- 24098216
TI  - 1-{3-(4-Methyl-phen-yl)-5-[5-(2-nitro-phen-yl)furan-2-yl]-4,5-di-hydro-1H-pyrazol
      1-yl}ethanone.
AB  - In the title compound, C22H19N3O4, the dihedral angle between the furan and
      pyrazole rings is 82.73 (19) degrees  while the dihedral angles between the furan
      and pyrazole rings and their attached benzene rings are 31.93 (18) and 1.88 (18)
      degrees , respectively. In the crystal, inversion dimers linked by pairs of C-H?O
      hydrogen bonds generate R 2 (2)(16) loops. In addition, weak C-H?pi and aromatic
      pi-pi stacking [minimum centroid-centroid distance = 3.5374 (17) A] inter-actions
      are observed. 

PMID- 24098217
TI  - Ethyl N-(2-acetyl-3-oxo-1-phenyl-but-yl)carbamate.
AB  - In the title compound, C15H19NO4, all three carbonyl groups are syn-oriented with
      respect to the methine group attached to the phenyl ring. The mean planes of the
      phenyl ring and ethyl carbamate moiety form a dihedral angle of 65.2 (1) degrees
      . In the crystal, mol-ecules related by translation in [100] are linked into
      chains via N-H?O hydrogen bonds. 

PMID- 24098218
TI  - 2-Di-chloro-methyl-N-ethyl-5-(1-phenyl-silolan-1-yl)cyclo-pent-3-enecarboxamide.
AB  - In the title compound, C19H25Cl2NOSi, the NH group and the carbonyl O atom of the
      amide fragment are involved in an inter-molecular N-H?O hydrogen bond forming
      chains of mol-ecules. The plane of the benzene ring forms a dihedral angle of
      50.5 (2) degrees  with respect to the silolane ring and an angle of 49.74 (2)
      degrees  with the cyclo-pentyl moiety. 

PMID- 24098219
TI  - tert-Butyl N-{[5-(5-oxohexa-namido)-pyridin-2-yl]amino}-carbamate.
AB  - In the crystal structure of the title compound, C16H24N4O4, mol-ecules are linked
      by N-H?O hydrogen bonds between the carbonyl groups of the carbamoyl and amido
      functional groups and the amino groups, and by N-H?N hydrogen bonds between the
      amino group and the pyridine ring, forming two-dimensional networks parallel to
      the ab plane. 

PMID- 24098220
TI  - 8-Bromo-3-(4-ethyl-phen-yl)-1-phenyl-3,3a,4,9b-tetra-hydro-1H-chromeno[4,3
      c]isoxazole-3a-carbo-nitrile.
AB  - In the title compound, C25H21BrN2O2, the fused isoxazolidine ring adopts an
      envelope conformation with the N atom at the flap and the mean plane of the ring
      makes dihedral angles of 54.37 (12) and 87.32 (13) degrees , respectively, with
      the adjacent phenyl and benzene rings. The tetra-hydro-pyran ring has a half
      chair conformation. In the crystal, mol-ecules are linked into a double-column
      structure along the b-axis direction through weak C-H?O and C-H?pi inter-actions.

PMID- 24098221
TI  - 4-Hy-droxy-6-methyl-pyridin-2(1H)-one.
AB  - In the crystal structure of the title compound, C6H7NO2, N-H?O and O-H?O hydrogen
      bonds link the mol-ecules, forming a zigzag array along [001] and a layer
      structure parallel to the ab plane. 

PMID- 24098222
TI  - 3,22-Dioxa-11,14-di-aza-penta-cyclo-[12.8.0.0(2,11).0(5,10).0(15,20)]docosa
      5(10),6,8,15(20),16,18-hexa-ene-4,21-dione.
AB  - In the title compound, C18H14N2O4, the piperazine ring adopts a chair
      conformation and the dihedral angle between the aromatic rings is 13.09 (9)
      degrees . In the crystal, mol-ecules are linked along the c axis by C-H?pi and
      N?pi [H(N)-centroid distances = 2.8030 (2) and 3.376 (2) A] inter-actions between
      neighbouring mol-ecules. 

PMID- 24098223
TI  - 2-Tri-fluoro-methyl-10H-benzo[4,5]imidazo[1,2-a]pyrimidin-4-one.
AB  - In the mol-ecule of the title compound, C11H6F3N3O, the three fused rings of the
      benzo[4,5]imidazo[1,2-a]pyrimidine unit are essentially coplanar, the maximum
      deviation from the mean plane being 0.096 (2) A. In the crystal, N-H?O hydrogen
      bonds link the mol-ecules into chains running along the b-axis direction. 

PMID- 24098224
TI  - N-(2-Bromo-phen-yl)-1,3-selenazolo[5,4-b]pyridin-2-amine.
AB  - The mol-ecular structure of the title mol-ecule, C12H8BrN3Se, is built up from
      fused selenazolo and pyridine rings, linked to a 2-bromo-aniline group. In the
      crystal, pairs of mol-ecules are linked by N-H?N hydrogen bonds into dimers,
      forming eight-membered ring motifs. 

PMID- 24098225
TI  - N-(2-Methyl-phen-yl)-1,2-benzoselen-azol-3(2H)-one.
AB  - IN THE TITLE EBSELEN [SYSTEMATIC NAME: (2-phenyl-1,2-benzoisoselenazol-3-(2H)
      one)] analogue, C14H11NOSe, the benzisoselenazolyl moiety (r.m.s. deviation =
      0.0209 A) is nearly perpendicular to the N-arenyl ring, making a dihedral angle
      of 78.15 (11) degrees . In the crystal, mol-ecules are linked by C-H?O and Se?O
      inter-actions into chains along the c-axis direction. The Se?O distance [2.733
      (3) A] is longer than that in Ebselen (2.571 (3) A]. 

PMID- 24098226
TI  - 5-Chloro-2-(thio-phen-2-yl)-1-(thio-phen-2-ylmeth-yl)-1H-benzimidazole-6-chloro-2
      (thiophen-2-yl)-1-(thiophen-2-ylmethyl)-1H-benzimidazole (0.94/0.06).
AB  - There are two independent mol-ecules in the asymmetric unit of the title
      compound, C16H11ClN2S2. The structure exhibits rotational disorder of the 2-thio
      phen-2-yl substituent in each of the unique mol-ecules with a major:minor
      component ratio of 0.927 (2):0.073 (2). For one of the symmetry-unique molecules,
      6.0 (2)% of the sites are occupied by the 6-chloro-isomer. The major component
      thio-phene rings make dihedral angles of 38.90 (12) and 36.32 (11) degrees  with
      the benzimidazole rings in the two independent mol-ecules. In the crystal, mol
      ecules are linked into chains parallel to [100] via weak C-H?N inter-actions. 

PMID- 24098227
TI  - 3-(3-Methyl-phen-yl)-5-(quinolin-8-yl-meth-oxy)-1,2,4-oxa-diazole monohydrate.
AB  - In the title compound, C19H15N3O2.H2O, the oxa-diazole ring and the quinoline
      unit are almost coplanar, making a dihedral angle of 7.66 (8) degrees . The
      dihedral angle between the benzene ring and the quinoline system is 25.95 (8)
      degrees  while that between the benzene and the oxa-diazole rings is 18.88 (9)
      degrees . The water mol-ecule is hydrogen bonded to an oxa-diazole N atom and to
      the quinoline N atom. In the crystal, these units are linked via C-H?O hydrogen
      bonds, forming two-dimensional net-works lying parallel to the ab plane. 

PMID- 24098228
TI  - 9-[(E)-2-(4-Chloro-phen-yl)ethen-yl]-3,3,6,6-tetra-methyl-2,3,4,5,6,7,8,9-octa
      hydro-1H-xanthene-1,8-dione.
AB  - In the title compound, C25H27ClO3, each of the cyclo-hexenone rings adopts an
      envelope conformation, whereas the six-membered pyran ring adopts a flattened
      boat conformation, with the O and methine C atoms deviating from the plane of the
      other four atoms. The C=C double bond is in the trans conformation. In the
      crystal, weak C-H?O hydrogen bonds link the mol-ecules into chains running
      parallel to the b axis. 

PMID- 24098229
TI  - Amino-[(1H-benzimidazol-2-yl)amino]-methaniminium 4-methyl-benzene-sulfonate.
AB  - The asymmetric unit of the title salt, C8H10N5 (+).C7H7O3S(-), consists of two
      amino-[(1H-benzimidazol-2-yl)amino]-meth-an-im-inium cations and two 4-methyl
      benzene-sulfonate anions. The cations are each stabilized by intra-molecular N
      H?N hydrogen bonds between the free amino groups and the imine N atoms of the
      benzimidazole units, forming S(6) ring motifs. In the crystal, cations and anions
      are linked by N-H?O and C-H?O hydrogen bonds, forming a three-dimensional supra
      molecular framework. Two strong pi-pi stacking inter-actions [centroid-centroid
      distances = 3.4112 (14) and 3.4104 (14) A] also occur between the centroids of
      the imidazole rings of like cations. 

PMID- 24098230
TI  - [(4E)-3-Ethyl-1-methyl-2,6-di-phenyl-piperidin-4-yl-idene]amino 3-methyl
      benzoate.
AB  - In the title compound, C28H30N2O2, the piperidine ring exists in a chair
      conformation with an equatorial orientation of the phenyl rings and methyl group
      substituted on the heterocycle. In the crystal, C-H?pi inter-actions result in
      chains of mol-ecules running parallel to the a-axis direction. 

PMID- 24098231
TI  - 4-Meth-oxy-anilinium 2-carb-oxy-4,5-di-chloro-benzoate.
AB  - In the title salt C7H10NO(+).C8H3Cl2O4 (-) the benzene rings of the cation and
      anion are essentially parallel [inter-ring dihedral angle 4.8 (2) degrees ]. In
      the anion the carb-oxy-lic acid and carboxyl-ate groups make dihedral angles of
      19.0 (2) and 79.5 (2) degrees , respectively, with the benzene ring. Aminium N
      H?O, carb-oxy-lic acid O-H?O and weak aromatic C-H?O hydrogen-bonding
      associations with carboxyl O-atom acceptors together with cation-anion pi-pi ring
      inter-actions [minimum ring centroid separation = 3.734 (3) A] give rise to a
      sheet structure lying parallel to (001). 

PMID- 24098232
TI  - 2-(2-Methyl-benzo-yl)benzoic acid: catemeric hydrogen bonding in a gamma-keto
      acid.
AB  - The crystal structure of the title compound, C15H12O3, displays catemeric
      aggregation involving O-H?O hydrogen bonds progressing from the carboxyl group of
      one mol-ecule to the ketone O atom of another glide-related neighbor. The mol
      ecule is twisted, with the toluene 80.61 (3) degrees  out of plane with respect
      to the phenyl group of the benzoic acid. The acid group makes a dihedral angle of
      13.79 (14) degrees  with the attached phenyl ring. The mol-ecules are achiral,
      but the space group glide planes create alternating conformational chirality in
      the chain units. The four hydrogen-bonding chains progress along [001] in an A-A
      B-B pattern (right-to-left versus left-to-right), and are related to each other
      by the center of symmetry at (0.5, 0.5, 0.5) in the chosen cell. There is one
      close contact (2.54 A) between a phenyl H atom and the acid carbonyl from a
      symmetry-related mol-ecule. 

PMID- 24098233
TI  - 4-{(E)-[2-(Pyridin-3-ylcarbon-yl)hydrazinyl-idene]meth-yl}phenyl acetate.
AB  - The title compound, C15H13N3O3, exists in the E conformation with respect to the
      azo-methane C=N double bond. The pyridyl and phenyl rings form dihedral angles of
      35.67 (8) and 36.65 (7) degrees , respectively with the central C(=O)N2C unit. In
      the crystal, N-H?O and C-H?O hydrogen bonds connect the mol-ecules into chains
      along the b axis. Another C-H?O inter-action connects mol-ecules along the c-axis
      direction, forming layers. 

PMID- 24098234
TI  - (4-Hy-droxy-3-methyl-phen-yl)(phen-yl)methanone.
AB  - In the title compound, C14H12O2, the benzene rings make a dihedral angle of 58.84
      (12) degrees . In the crystal, mol-ecules are linked into chains along the b-axis
      direction by O-H?O hydrogen bonds. These chains are further linked by C-H?O
      hydrogen bonds, forming layers parallel to the bc plane. 

PMID- 24098235
TI  - (3aR,6S,7aR)-7a-Chloro-2-[(4-nitro-phen-yl)sulfon-yl]-1,2,3,6,7,7a-hexa-hydro
      3a,6-ep-oxy-iso-indole.
AB  - In the title compound, C14H13ClN2O5S, the chlorine-substituted tetrahydrofuran
      ring adopts a twist conformation and the other tetra-hydro-furan ring an envelope
      conformation with the O atom as the flap. The pyrrolidine ring adopts a twist
      conformation. In the crystal, C-H?O hydrogen bonds link the mol-ecules into
      zigzag chains running along the b-axis direction. 

PMID- 24098236
TI  - Methyl 2-((2Z,5Z)-2-{(E)-2-[1-(4-hy-droxy-phen-yl)ethyl-idene]hydrazin-1-yl
      idene}-4-oxo-3-phenyl-1,3-thia-zolidin-5-yl-idene)acetate.
AB  - In the title compound, C20H17N3O4S, all non-H atoms, except those of the phenyl
      ring, are approximately coplanar [maximum deviation = 0.2214 (1) A], and the
      dihedral angle between their best plane and the benzene ring is 53.13 (1) degrees
      . A short intra-molecular O?S contact of 2.838 (1) A is formed between the ester
      carbonyl O atom and the S atom of the thia-zolidine ring. In the crystal, mol
      ecules associated via O-H?O, C-H?O and C-H?S hydrogen bonds form layers parallel
      to (010), with only C-H?O-type short contacts between the mol-ecules in adjacent
      layers. 

PMID- 24098237
TI  - rac-Methyl (3aR*,4S*,5R*,7aR*)-5,7a-bis-(acet-yloxy)-3-oxo-2-phenyl-octa-hydro-1H
      iso-indole-4-carboxyl-ate.
AB  - The title molecule, C20H23NO7, the product of nucleophilic cleavage of the 3a,6
      ep-oxy bridge in 1-oxo-2-phenyl-octa-hydro-3a,6-ep-oxy-iso-indole-7-carboxyl-ate,
      comprises a cis-fused bicyclic system containing a 2-pyrrolidinone ring in an
      envelope conformation (with the C atom bearing the carboxyl-ate substituent as
      the flap) and a cyclo-hexane ring in a chair conformation. The carboxyl-ate
      substituent occupies the equatorial position, whereas the two acet-yloxy
      substituents are in axial positions. The N atom has a trigonal-planar geometry,
      the sum of the bond angles being 359.3 (3) degrees . The dihedral angle between
      the mean plane of the four planar atoms of the pyrrolidinone ring and the phenyl
      ring is 25.98 (6) degrees . In the crystal, mol-ecules are linked into zigzag
      chains along the c-axis direction by C-H?O hydrogen bonds. 

PMID- 24098238
TI  - Desvenlafaxinium chloranilate ethyl acetate solvate.
AB  - In the cation of the title compound, C16H26NO2 (+).C6HCl2O4 (-).C4H8O2, the 1-hy
      droxy-cyclo-hexyl ring adopts a slightly distorted chair conformation. The
      dihedral angle between the mean planes of the 1-hy-droxy-cyclo-hexyl and 4-hy
      droxy-phenyl rings is 84.0 (8) degrees . In the anion, the hydroxyl H atom is
      twisted slightly out of the ring plane with a C-C-O-H torsion angle of -171.9
      degrees . Disorder was modeled for the methyl group of the acetate group in the
      solvate with an occupancy ratio of 0.583 (15): 0.417 (15). In the crystal, O-H?O
      hydrogen bonds are observed between cations and between cations and anions, while
      bifuricated N-H?(O,O) cation-anion hydrogen bonds are also present, forming
      chains along [010] and [100]. In addition weak cation-anion and cation-solvate C
      H?O inter-actions occur. 

PMID- 24098239
TI  - 12-(2-Hy-droxy-6-oxo-cyclo-hex-1-en-yl)-9,10-di-hydro-8H-benzo[a]xanthen-11(12H)
      one.
AB  - In the xanthenone system of the title compound, C23H20O4, the pyran ring has a
      maximum deviation of 0.111 (1) A from planarity and the outer cyclo-hexene ring
      exhibits a puckered conformation. The three methyl-ene C atoms of the cyclo
      hexene ring bonded to the pyran unit are disordered over two sets of sites
      [occupancies = 0.570 (3) and 0.430 (3)]. In the crystal, mol-ecules are linked by
      C-H?O and O-H?O hydrogen bonds, forming a two-dimensional network parallel to
      (110). A C-H?pi inter-action occurs between these networks. 

PMID- 24098240
TI  - 5,6-Dimeth-yl-1,10-phenanthroline.
AB  - In the title compound, C14H12N2, the N?N distance is 2.719 (1) A. The N-C-C-N
      torsion angle [0.9 (1) degrees ] is close to the ideal value of 0 degrees  as
      expected. Bond lengths and angles are consistent with those observed for
      [1,10]phenanthroline and coordinated 5,6 dimeth-yl[1,10]phenanthroline. In the
      crystal, C-H?N hydrogen bonds link the mol-ecules into C(4) chains running
      parallel to the b axis. Weak pi-pi inter-actions between benzene and pyridine
      rings [centroid-centroid distance = 3.5337 (7) A] and between benzene rings
      [centroid-centroid distances = 3.6627 (7) and 3.8391 (7)A] also occur. 

PMID- 24098241
TI  - 2,6-Dimethyl-N-(2-methyl-phen-yl)-1,3-dioxan-4-amine.
AB  - In the title compound, C13H19NO2, the dioxane ring adopts a chair conformation
      and its mean plane makes a dihedral angle of 45.36 (8) degrees  with the phenyl
      ring. In the crystal, mol-ecules are linked by pairs of N-H?O hydrogen bonds,
      forming inversion dimers with R (2) 2(12) ring motifs. These dimers are
      consolidated by pairs of C-H?O hydrogen bonds with R (2) 2(8) ring motifs. 

PMID- 24098242
TI  - Methyl 4-(benz-yloxy)-3-meth-oxy-benzo-ate.
AB  - In the title compound, C16H16O4, the aromatic rings are almost normal to one
      another, making a dihedral angle of 85.81 (10) degrees . In the crystal, mol
      ecules are linked by C-H?O hydrogen bonds, forming chains propagating along the b
      axis direction. There are also C-H?pi inter-actions present which link the
      chains, forming two-dimensional networks lying parallel to (102). 

PMID- 24098243
TI  - (2E)-4-(4-Bromo-phen-yl)-2-{(2Z)-[1-(4-methyl-phen-yl)ethyl-idene]hydrazinyl
      idene}-3-phenyl-2,3-di-hydro-1,3-thia-zole.
AB  - In the title compound, C24H20BrN3S, the di-hydro-thia-zole ring is approximately
      planar, with a maximum deviation of 0.008 (2) A, and is twisted with respect to
      the 4-bromo-phenyl ring, the phenyl ring and methyl-phenyl ring, making dihedral
      angles of 47.96 (8), 59.52 (9) and 16.96 (9) degrees , respectively. In the
      crystal, weak C-H?pi inter-actions link inversion-related mol-ecules into supra
      molecular dimers. 

PMID- 24098244
TI  - 4,6-Di-tert-butyl-2,3-di-hydroxy-benzalde-hyde.
AB  - The title compound, C15H22O3, crystallizes with two independent mol-ecules in the
      asymmetric unit. In each mol-ecule, one hy-droxy group (at position 2) is
      involved in an intra-molecular O-H?O hydrogen bond, and another one (at position
      3) exhibits bifurcated hydrogen-bonding being involved in intra- and inter
      molecular O-H?O inter-actions. In the crystal, O-H?O hydrogen bonds link
      alternating independent mol-ecules into chains running along [010]. 

PMID- 24098245
TI  - Methyl 4-(tri-fluoro-meth-yl)-1H-pyrrole-3-carboxyl-ate.
AB  - In the title compound, C7H6F3NO2, all the non-H atoms except for one of the F
      atoms lie on a crystallographic mirror plane. In the crystal, the mol-ecules are
      linked into inversion dimers by pairs of C-H?F inter-actions, forming R 2 (2)(10)
      loops. These dimers are connected into C(6) chains along [001] through N-H?O
      hydrogen bonds. Aromatic pi-pi stacking inter-actions [centroid-centroid
      separation = 3.8416 (10) A degrees ] connect the mol-ecules into a three
      dimensional network. 

PMID- 24098246
TI  - 3-Chloro-N-[N-(furan-2-carbon-yl)hydrazinocarbo-thio-yl]benzamide.
AB  - In the title compound C13H10ClN3O3S, the benzoyl group maintains its trans
      conformation against the thiono group about the C-N bond and the intra-molecular
      hydrogen bond between the benzoyl O atom and thio-amide H atom. In the crystal, N
      H?O and C-H?O hydrogen bonds link the mol-ecules, forming chains along the b-axis
      direction. In addition, C-H?pi inter-actions occur between a phenyl H atom and
      the furan ring. 

PMID- 24098247
TI  - 4-Chloro-2-(2-chloro-benzoyl)phenol.
AB  - In the title mol-ecule, C13H8Cl2O2, the dihedral angle between the benzene rings
      is 74.53 (9) degrees . An intra-molecular O-H?O hydrogen bond leading to a S(6)
      ring is observed. In the crystal, the mol-ecules are connected into a three
      dimensional network by C-H?O and pi-pi [inter-centroid distance = 3.6254 (10) A]
      inter-actions. 

PMID- 24098248
TI  - Methyl 9-hy-droxy-15-methyl-2-oxo-11-(pyren-1-yl)-10-oxa-15-aza-tetra-cyclo
      [7.6.0.0(1,12).0(3,8)]penta-deca-3(8),4,6-triene-12-carboxyl-ate.
AB  - In the title compound, C32H25NO5, the furan and pyrrole rings each adopt an
      envelope conformation, the respective flap atoms being the C atom bearing the
      pyrene substituent and the CH2 atom adjacent to the N atom. The mol-ecular
      conformation is stabilized by an intra-molecular O-H?N hydrogen bond. In the
      crystal, C-H?O contacts link the mol-ecules, forming a two-dimensional network
      parallel to (001). 

PMID- 24098249
TI  - Methyl 8-bromo-3-[1-(4-meth-oxy-phen-yl)-4-oxo-3-phenyl-azetidin-2-yl]-1-methyl
      1,2,3,3a,4,9b-hexa-hydro-chromeno[4,3-b]pyrrole-3a-carboxyl-ate.
AB  - In the title compound, C30H29BrN2O5, the beta-lactam ring is essentially planar,
      with the O atom displaced from this plane by 0.856 (9) A, and forming dihedral
      angles of 24.35 (13) and 89.42 (14) degrees  with the planes of the benzene
      substituent groups on this ring. The tetra-hydro-pyran ring adopts an envelope
      conformation with the C atom bearing the beta-lactam ring as the flap. In the
      crystal, weak C-H?O hydrogen bonds with carboxyl and tetra-hydro-pyran O-atom
      acceptors give rise to a chain structure extending along the b-axis direction. 

PMID- 24098250
TI  - 2-[(E)-(Morpholin-4-yl-imino)-meth-yl]-6-(morpholin-4-ylmeth-yl)phenol.
AB  - The title compound, C16H23N3O3, contains two morpholine rings, each of which
      adopts a chair conformation. The mol-ecular conformation is stabilized by an
      intra-molecular O-H?N hydrogen bond, leading to a S(6) ring. In the crystal, mol
      ecules are linked into zigzag chains along the c-axis direction by C-H?O and C
      H?pi inter-actions. 

PMID- 24098252
TI  - Di-hydro-cyclam dimaleate [H2(cyclam)(maleate)2].
AB  - The asymmetric unit of the title mol-ecular salt [systematic name: 1,4,8,11
      tetraazacyclotetradecane-1,8-diium bis(3-carboxy-prop-2-enoate)], C10H26N4
      (2+).2C4H3O4 (-), contains two half-cations (both completed by crystallographic
      inversion symmetry) and two maleate anions. The cyclam macrocycles adopt trans
      III conformations, supported by two intra-molecular N-H?O hydrogen bonds. The O
      bonded H atom of each maleate ion is disordered over two positions with an
      occupancy ratio of 0.61 (5):0.39 (5): each one generates an intra-molecular O-H?O
      hydrogen bond. In the crystal, the cations are linked to the anions by N-H?O
      hydrogen bonds, generating [001] chains. 

PMID- 24098251
TI  - 3-(1H-Imidazol-1-yl)propanaminium picrate.
AB  - IN THE TITLE SALT [SYSTEMATIC NAME: 3-(1H-imidazol-1-yl)propanaminium 2,4,6-tri
      nitro-phenolate], C6H12N3 (+).C6H2N3O7 (-), there are five independent cation
      anion pairs (A, B, C, D, E) in the asymmetric unit. In the cation, the ammonium
      group is protonated with the amino-propyl group nearly at right angles to the
      mean plane of the imidazole ring showing C-N-C-C torsion angles ranging from 79.6
      (2) to 99.79 (19) degrees  in the five cations. The nitro groups in the anion are
      twisted from the benzene mean plane with maximum dihedral angles subtended by
      nitro substituents ortho to the phenolate O atom of 26.0 (2) and 37.3 (7) (A),
      28.9 (5) and 35.3 (1) (B), 34.7 (7) and 36.9 (7) (C), 14.7 (4) and 36.9 (2) (D)
      and 33.1 (1) and 35.4 (3) degrees  (E). In contrast, the nitro groups in the para
      positions lie much closer to the aromatic ring plane, subtending dihedral angles
      of 1.8 (3) (A), 3.5 (3) (B), 6.03 (C), 2.1 (3) (D) and 7.7 (1) degrees  (E).
      Disorder is observed for one O atom of an ortho nitro group in anion D with an
      occupancy ratio of 0.53 (5):0.47 (5). In the crystal, N-H?O cation-anion and N
      H?N cation-cation hydrogen bonds are observed, linking the ions into chains along
      [010]. In addition, weak C-H?O cation-anion inter-actions occur. 

PMID- 24098253
TI  - (E)-N-(1,3-Benzodioxol-5-yl)-1-(4-{[1-(prop-2-en-1-yl)-1H-1,2,3-triazol-4-yl]meth
      oxy}phen-yl)methanimine.
AB  - In the title compound, C20H18N4O3, the dihedral angles between the central
      benzene ring and the 1H-1,2,3-triazole ring and the fused benzene ring are 65.34
      (19) and 3.64 (18) degrees , respectively. The dioxole ring adopts a shallow
      envelope conformation, with the methyl-ene C atom displaced by 0.156 (5) A from
      the other four atoms (r.m.s. deviation = 0.007A). In the crystal, the mol-ecules
      are linked by C-H?O and C-H?N hydrogen bonds, generating a three-dimensional
      network. 

PMID- 24098254
TI  - tert-Butyl 4-{[2-amino-4-(2-hy-droxy-phen-yl)pyrimidin-5-yl]meth-yl}piperazine-1
      carboxyl-ate.
AB  - In the title compound, C20H27N5O3, the central piperazine ring adopts a chair
      conformation, with the N-bound carboxyl-ate and methyl-ene substituents occupying
      bis-ectional and equatorial orientations, respectively. A twist is evident
      between the aromatic rings [dihedral angle = 25.61 (9) degrees ] but an intra
      molecular O-H?N hydrogen bond persists between these. Supra-molecular tapes along
      [1-10] are formed in the crystal packing through N(amino)-H?O(hydrox-yl) and
      N(amino)-H?N(pyrimidin-yl) hydrogen bonds, and these are linked into layers in
      the ab plane by pi-pi inter-actions [inter-centroid distance between pyrimidinyl
      rings = 3.5919 (9) A]. 

PMID- 24098255
TI  - N-(4-Bromo-phen-yl)-2,6-dimethyl-1,3-dioxan-4-amine.
AB  - In the title compound, C12H16BrNO2, the dioxane ring adopts a chair conformation
      and its mean plane makes a dihedral angle of 60.63 (12) degrees  with the 4-bromo
      phenyl ring. In the crystal, mol-ecules are linked by pairs of N-H?O hydrogen
      bonds, forming inversion dimers with an R 2 (2)(8) ring motif. These dimers are
      consolidated by pairs of C-H?O hydrogen bonds with an R 2 (2)(16) ring motif.
      Adjacent dimers are connected via C-H?O hydrogen bonds, forming infinite chains
      propagating along the c-axis direction. 

PMID- 24098256
TI  - 3-(4-Hy-droxy-phen-yl)-1,5-bis-(pyridin-2-yl)pentane-1,5-dione.
AB  - In the title mol-ecule, C21H18N2O3, the pyridine rings make a dihedral angle of
      13.1 (1) degrees . The phenyl ring is approximately perpendicular to both of
      them, forming dihedral angles of 87.4 (1)and 81.9 (1) degrees . In the crystal,
      pairs of O-H?N hydrogen bonds link the mol-ecules into centrosymmetric dimers.
      Additional C-H?O, pi-pi [centroid-centroid distance = 3.971 (2) A] and C-H?pi
      inter-actions consolidate the dimers into a three-dimensional network. 

PMID- 24098257
TI  - 14a-Hy-droxy-12-methyl-10-(4-methyl-phen-yl)-8,9,9a,10,12,13,14,14a-octa-hydro
      10a,14-methano-5H-indeno-[2',1':4,5]azepino[3,4-b]pyrrolizine-5,15(7H,11H)-dione.
AB  - In the title compound, C27H28N2O3, each of the pyrrolidine rings adopts a twisted
      conformation, as does the cyclo-pentane ring. The indane ring has an r.m.s
      deviation of 0.0693 A. The dihedral angle between the mean plane of the
      pyrrolizine ring and indane system is 82.58 (1) degrees . The piperidine ring has
      the methyl substituent in an equatorial position and adopts a twisted chair
      conformation. The mol-ecular structure is stabilized by a weak intra-molecular O
      H?N inter-action. 

PMID- 24098258
TI  - N-(4-Acetyl-3-methyl-1-phenyl-1H-pyrazol-5-yl)-N-methyl-2-(2-methyl-4-oxo-3,4
      dihydroquinazolin-3-yl)benzamide.
AB  - In the title compound, C29H25N5O3, the dihedral angle between the benzene ring
      and the pendant quinazoline ring system (r.m.s. deviation = 0.036A) is 87.60 (17)
      degrees . The equivalent angle between the pyrazole ring and the phenyl group is
      70.0 (2) degrees . The dihedral angle between the benzene and pyrazole rings is
      30.7 (2) degrees  and overall, the mol-ecular conformation approximates to a Z
      shape. A short intra-molecular C-H?O contact occurs. In the crystal, the mol
      ecules are linked by Cpi-H?O-type hydrogen bonds and aromatic pi-pi stacking
      inter-actions [centroid-centroid distance = 3.860 (3) A], generating a three
      dimensional network. 

PMID- 24098259
TI  - (E)-2-{[1-(3,11-Dimethyl-4-methyl-ene-10-oxo-1-phenyl-4,5,10,11-tetra-hydro-1H
      benzo[b]pyrazolo-[3,4-f][1,5]diazo-cin-5-yl)ethyl-idene]amino}-N-methyl-N-(3
      methyl-1-phenyl-1H-pyrazol-5-yl)benzamide.
AB  - The central eight-membered ring of the title compound, C40H36N8O2, deviates from
      the ideal boat conformation because the bond between the exo-ethyl-ene group and
      the adjacent N atom is twisted by 60.0 (4) degrees  due to steric hindrance. Its
      adjacent benzene and pyrazole rings are oriented almost perpendicular to each
      other, making a dihedral angle of 85.8 (3) degrees . In the crystal, the mol
      ecules are linked by C(ar)-H?O hydrogen bonds, generating a three-dimensional
      network. 

PMID- 24098260
TI  - N,N'-Bis(3-bromo-2-hy-droxy-benzyl-idene)propane-1,3-di-amine.
AB  - In the title compound, C17H16Br2N2O2, the dihedral angle between the benzene
      rings is 57.7 (3) degrees . The conformation of the central N-C-C-C-N chain is
      gauche-anti [torsion angles = -64.2 (4) and -167.8 (4) degrees ]. Two intra
      molecular O-H?N hydrogen bonds occur. In the crystal, molecules are linked by
      pairs of C-H?O hydrogen bonds, forming inversion dimers. 

PMID- 24098261
TI  - 3'-[(1H-Indol-3-yl)carbon-yl]-1'-methyl-2-oxo-4'-(thio-phen-2-yl)-spiro-[indoline
      3,2'-pyrrolidine]-3'-carbo-nitrile.
AB  - In the title compound, C26H20N4O2S, the central pyrrolidine ring adopts a twist
      conformation on the C-C bond involving the spiro C atom. Its mean plane makes
      dihedral angles of 78.83 (14), 65.91 (15) and 44.49 (18) degrees  with the mean
      planes of the adjacent oxindole ring system, the indole system and the thio-phene
      ring, respectively. The indole and indoline units are essentially planar, with
      maximum deviations of 0.019 (3) and 0.090 (3) A, respectively. In the oxindole
      fused-ring system, the pyrrole ring adopts an envelope conformation with the
      spiro C atom as the flap. In the crystal, pairs of N-H?O hydrogen bonds link the
      mol-ecules, forming inversion dimers with an R (2) 2(8) ring motif. The dimers
      are linked by further N-H?O hydrogen bonds, forming a two-dimensional network
      lying parallel to (100). 

PMID- 24098262
TI  - 2-Amino-5-methyl-3-(2-oxo-2-phenyl-eth-yl)-7-phenyl-4,5,6,7-tetra-hydro-3H
      [1,2,4]triazolo[1,5-a]pyrimidin-8-ium bromide ethanol monosolvate.
AB  - In the title compound, C20H22N5O(+).Br(-).C2H6O, the tetra-hydro-pyrimidine ring
      of the bicyclic cation adopts a half-chair conformation with an equatorial
      orientation of the phenyl and methyl substituents. The amino group is nearly
      coplanar with the 1,2,4-triazole ring [interplanar angle = 4.08 (8) degrees ] and
      has a slightly pyramidal configuration. The mean planes of the triazole ring and
      the benzene ring of the phenacyl group form a dihedral angle of 88.58 (7) degrees
      . In the crystal, N-H?Br, N-H?O and O-H?Br hydrogen bonds link the cations,
      anions and ethanol mol-ecules into layers parallel to the bc plane. 

PMID- 24098263
TI  - 6-[(4'-Ethoxycarbonyl-[1,1'-biphenyl]-4-yl)oxy]hexanoic acid.
AB  - In the title compound, C21H24O5, the dihedral angle between the benzene rings is
      19.57 (15) degrees . In the crystal, the mol-ecular arrangement makes up head-to
      head centrosymmetric dimers assembled by pairs of O-H?O bonds; this arrangement
      builds a graph-set ring motif of R (2) 2(8). The dimers are linked into a tape
      running along the b-axis direction through C-H?O inter-actions. The packing is
      further consolidated by C-H?pi inter-actions, forming layers parallel to (10-2). 

PMID- 24098264
TI  - N-(1-Allyl-1H-indazol-5-yl)-4-meth-oxy-benzene-sulfonamide hemihydrate.
AB  - In the title compound, C17H17N3O3 (.)0.5H2O, the indazole system makes a dihedral
      angle of 46.19 (8) degrees  with the plane through the benzene ring and is nearly
      perpendicular to the allyl group, as indicated by the dihedral angle of 81.2 (3)
      degrees . In the crystal, the water mol-ecule, disordered over two sites related
      by an inversion center, forms O-H?N bridges between indazole N atoms of two
      sulfonamide mol-ecules. It is also connected via N-H?O inter-action to the third
      sulfonamide mol-ecule; however, due to the water mol-ecule disorder, only every
      second mol-ecule of sulfonamide participates in this inter-action. This missing
      inter-action results in a slight disorder of the sulfonamide S,O and N atoms
      which are split over two sites with half occupancy. With the help of C-H?O
      hydrogen bonds, the mol-ecules are further connected into a three-dimensional
      network. 

PMID- 24098265
TI  - N,N'-(2-Hy-droxy-propane-1,3-di-yl)bis-(2-hy-droxy-benzamide) monohydrate.
AB  - In the title hydrate, C17H18N2O5.H2O, the complete organic mol-ecule is generated
      by a crystallographic mirror plane with one C and one O atom lying on the mirror
      plane. The O atom of the water mol-ecule has m site symmetry. Two symmetry
      related intra-molecular O-H?O hydrogen bonds complete S(6) rings in the organic
      mol-ecule. In the crystal, the components are linked into (010) sheets by O-H?O
      and N-H?O hydrogen bonds. 

PMID- 24098266
TI  - N-(2-Nitro-phen-yl)furan-2-carboxamide.
AB  - In the title furan-carboxamide derivative, C11H8N2O4, the benzene and furan rings
      are rotated from the mean plane of the central fragment by 2.68 (5) and 7.03 (4)
      degrees , respectively. The nitro group forms a dihedral angle of 10.15 (5)
      degrees  with the adjacent benzene ring. In the crystal, mol-ecules are linked by
      weak C-H?O inter-actions, forming helical chains running along [010]. 

PMID- 24098267
TI  - 2,2'-{[(1E,1'E)-(Cyclo-hexane-1,4-diyl)-bis(aza-nylyl-idene)]bis-(ethan-1-yl-1-yl
      idene)}diphenol.
AB  - The title compound, C22H26N2O2, crystallizes with three independent mol-ecules,
      two of which are situated on inversion centers, so the asymmetric unit contains
      two independent half-mol-ecules and one mol-ecule in a general position. The two
      hy-droxy groups in each mol-ecule are involved in intra-molecular O-H?N hydrogen
      bonds, which generate S(6) rings. In the crystal, weak inter-molecular C-H?pi
      inter-actions link the mol-ecules into two crystallographically independent
      columns propagating along [001]; one column consists of mol-ecules in general
      positions, while the other column is built from alternating independent
      centrosymmetric mol-ecules. 

PMID- 24098268
TI  - 2-Benzyl-5-meth-oxy-isoindoline-1,3-dione.
AB  - The title N-benzyl-phthalimide derivative, C16H13NO3, consists of two planar
      moieties, viz. the phthalimide system (r.m.s. deviation = 0.007 A) and the phenyl
      ring, which make a dihedral angle of 84.7 (6) degrees . The meth-oxy group is
      almost coplanar with the phathalimide ring, as shown by the C-C-O-C torsion angle
      of -171.5 (2) degrees . In the crystal, the mol-ecules are self-assembled via non
      classical C-H?O hydrogen bonds, forming a tape motif along [110]. 

PMID- 24098269
TI  - 4'-Acetyl-3''-carbamoyl-[1,1':3',1''-terphen-yl]-2-carb-oxy-lic acid.
AB  - In the title m-terphenyl derivative, C22H17NO4, the dihedral angles between the
      aromatic rings of the benzoic acid-acetophenone, acetophenone-benzamide and
      benzoic acid-benzamide units are 45.39 (8), 48.02 (8) and 42.93 (8) degrees ,
      respectively. The carbamoyl and carboxyl groups are disordered with a refined
      occupancy ratio of 0.558 (15):0.442 (15). In the crystal, mol-ecules are linked
      through O-H?O and N-H?O hydrogen bonds between terminal carboxyl and carbamoyl
      groups in a bidentate manner, and anti-parallel helices are formed which extend
      along the b-axis direction. 

PMID- 24098271
TI  - Making myelin basic protein -from mRNA transport to localized translation.
AB  - In the central nervous system (CNS) of most vertebrates, oligodendrocytes enwrap
      neuronal axons with extensions of their plasma membrane to form the myelin
      sheath. Several proteins are characteristically found in myelin of which myelin
      basic protein (MBP) is the second most abundant one after proteolipid protein.
      The lack of functional MBP in rodents results in a severe hypomyelinated
      phenotype in the CNS demonstrating its importance for myelin synthesis. Mbp mRNA
      is transported from the nucleus to the plasma membrane and is translated locally
      at the axon-glial contact site. Axonal properties such as diameter or electrical
      activity influence the degree of myelination. As oligodendrocytes can myelinate
      many axonal segments with varying properties, localized MBP translation
      represents an important part of a rapid and axon-tailored synthesis machinery.
      MBP's ability to compact cellular membranes may be problematic for the integrity
      of intracellular membranous organelles and can also explain why MBP is
      transported in oligodendrocytes in the form of an mRNA rather than as a protein.
      Here we review the recent findings regarding intracellular transport and
      signaling mechanisms leading to localized translation of Mbp mRNA in
      oligodendrocytes. More detailed insights into the MBP synthesis pathway are
      important for a better understanding of the myelination process and may foster
      the development of remyelination therapies for demyelinating diseases. 

PMID- 24098270
TI  - Differential vulnerability of interneurons in the epileptic hippocampus.
AB  - The loss of hippocampal interneurons has been considered as one reason for the
      onset of temporal lobe epilepsy (TLE) by shifting the excitation-inhibition
      balance. Yet, there are many different interneuron types which show differential
      vulnerability in the context of an epileptogenic insult. We used the
      intrahippocampal kainate (KA) mouse model for TLE in which a focal, unilateral KA
      injection induces status epilepticus (SE) followed by development of granule cell
      dispersion (GCD) and hippocampal sclerosis surrounding the injection site but not
      in the intermediate and temporal hippocampus. In this study, we characterized the
      loss of interneurons with respect to septotemporal position and to differential
      vulnerability of interneuron populations. To this end, we performed
      intrahippocampal recordings of the initial SE, in situ hybridization for glutamic
      acid decarboxylase 67 (GAD67) mRNA and immunohistochemistry for parvalbumin (PV)
      and neuropeptide Y (NPY) in the early phase of epileptogenesis at 2 days and at
      21 days after KA injection, when recurrent epileptic activity and GCD have fully
      developed. We show that SE extended along the entire septotemporal axis of both
      hippocampi, but was stronger at distant sites than at the injection site. There
      was an almost complete loss of interneurons surrounding the injection site and
      expanding to the intermediate hippocampus already at 2 days but increasing until
      21 days after KA. Furthermore, we observed differential vulnerability of PV- and
      NPY-expressing cells: while the latter were lost at the injection site but
      preserved at intermediate sites, PV-expressing cells were gone even at sites more
      temporal than GCD. In addition, we found upregulation of GAD67 mRNA expression in
      dispersed granule cells and of NPY staining in ipsilateral granule cells and ipsi
      and contralateral mossy fibers. Our data thus indicate differential survival
      capacity of interneurons in the epileptic hippocampus and compensatory plasticity
      mechanisms depending on the hippocampal position. 

PMID- 24098272
TI  - Integration of ultra-high field MRI and histology for connectome based research
      of brain disorders.
AB  - Ultra-high field magnetic resonance imaging (MRI) became increasingly relevant
      for in vivo neuroscientific research because of improved spatial resolutions.
      However, this is still the unchallenged domain of histological studies, which
      long played an important role in the investigation of neuropsychiatric disorders.
      While the field of biological psychiatry strongly advanced on macroscopic levels,
      current developments are rediscovering the richness of immunohistological
      information when attempting a multi-level systematic approach to brain function
      and dysfunction. For most studies, histology sections lost information on three
      dimensional reconstructions. Translating histological sections to 3D-volumes
      would thus not only allow for multi-stain and multi-subject alignment in post
      mortem data, but also provide a crucial step in big data initiatives involving
      the network analyses currently performed with in vivo MRI. We therefore
      investigated potential pitfalls during integration of MR and histological
      information where no additional blockface information is available. We
      demonstrated that strengths and requirements from both methods can be effectively
      combined at a spatial resolution of 200 MUm. However, the success of this
      approach is heavily dependent on choices of hardware, sequence and
      reconstruction. We provide a fully automated pipeline that optimizes histological
      3D reconstructions, providing a potentially powerful solution not only for
      primary human post mortem research institutions in neuropsychiatric research, but
      also to help alleviate the massive workloads in neuroanatomical atlas
      initiatives. We further demonstrate (for the first time) the feasibility and
      quality of ultra-high spatial resolution (150 MUm isotopic) imaging of the entire
      human brain MRI at 7T, offering new opportunities for analyses on MR-derived
      information. 

PMID- 24098273
TI  - Auditory and cognitive factors underlying individual differences in aided speech
      understanding among older adults.
AB  - This study was designed to address individual differences in aided speech
      understanding among a relatively large group of older adults. The group of older
      adults consisted of 98 adults (50 female and 48 male) ranging in age from 60 to
      86 (mean = 69.2). Hearing loss was typical for this age group and about 90% had
      not worn hearing aids. All subjects completed a battery of tests, including
      cognitive (6 measures), psychophysical (17 measures), and speech-understanding (9
      measures), as well as the Speech, Spatial, and Qualities of Hearing (SSQ) self
      report scale. Most of the speech-understanding measures made use of competing
      speech and the non-speech psychophysical measures were designed to tap phenomena
      thought to be relevant for the perception of speech in competing speech (e.g.,
      stream segregation, modulation-detection interference). All measures of speech
      understanding were administered with spectral shaping applied to the speech
      stimuli to fully restore audibility through at least 4000 Hz. The measures used
      were demonstrated to be reliable in older adults and, when compared to a
      reference group of 28 young normal-hearing adults, age-group differences were
      observed on many of the measures. Principal-components factor analysis was
      applied successfully to reduce the number of independent and dependent (speech
      understanding) measures for a multiple-regression analysis. Doing so yielded one
      global cognitive-processing factor and five non-speech psychoacoustic factors
      (hearing loss, dichotic signal detection, multi-burst masking, stream
      segregation, and modulation detection) as potential predictors. To this set of
      six potential predictor variables were added subject age, Environmental Sound
      Identification (ESI), and performance on the text-recognition-threshold (TRT)
      task (a visual analog of interrupted speech recognition). These variables were
      used to successfully predict one global aided speech-understanding factor,
      accounting for about 60% of the variance. 

PMID- 24098274
TI  - The use of dendrograms to describe the electrical activity of motoneurons
      underlying behaviors in leeches.
AB  - The present manuscript aims at identifying patterns of electrical activity
      recorded from neurons of the leech nervous system, characterizing specific
      behaviors. When leeches are at rest, the electrical activity of neurons and
      motoneurons is poorly correlated. When leeches move their head and/or tail, in
      contrast, action potential (AP) firing becomes highly correlated. When the head
      or tail suckers detach, specific patterns of electrical activity are detected.
      During elongation and contraction the electrical activity of motoneurons in the
      Medial Anterior and Dorsal Posterior nerves increase, respectively, and several
      motoneurons are activated both during elongation and contraction. During
      crawling, swimming, and pseudo-swimming patterns of electrical activity are
      better described by the dendrograms of cross-correlations of motoneurons pairs.
      Dendrograms obtained from different animals exhibiting the same behavior are
      similar and by averaging these dendrograms we obtained a template underlying a
      given behavior. By using this template, the corresponding behavior is reliably
      identified from the recorded electrical activity. The analysis of dendrograms
      during different leech behavior reveals the fine orchestration of motoneurons
      firing specific to each stereotyped behavior. Therefore, dendrograms capture the
      subtle changes in the correlation pattern of neuronal networks when they become
      involved in different tasks or functions. 

PMID- 24098275
TI  - Validation and extension of the reward-mountain model.
AB  - The reward-mountain model relates the vigor of reward seeking to the strength and
      cost of reward. Application of this model provides information about the stage of
      processing at which manipulations such as drug administration, lesions,
      deprivation states, and optogenetic interventions act to alter reward seeking.
      The model has been updated by incorporation of new information about frequency
      following in the directly stimulated neurons responsible for brain stimulation
      reward and about the function that maps objective opportunity costs into
      subjective ones. The behavioral methods for applying the model have been updated
      and improved as well. To assess the impact of these changes, two related
      predictions of the model that were supported by earlier work have been retested:
      (1) altering the duration of rewarding brain stimulation should change the pulse
      frequency required to produce a reward of half-maximal intensity, and (2) this
      manipulation should not change the opportunity cost at which half-maximal
      performance is directed at earning a maximally intense reward. Prediction 1 was
      supported in all six subjects, but prediction 2 was supported in only three. The
      latter finding is interpreted to reflect recruitment, at some stimulation sites,
      of a heterogeneous reward substrate comprising dual, parallel circuits that
      integrate the stimulation-induced neural signals. 

PMID- 24098276
TI  - Developmental trajectories of associative memory from childhood to adulthood: a
      behavioral and neuroimaging study.
AB  - Episodic memory refers to the capacity to bind multimodal memories to constitute
      a unique personal event. Most developmental studies on episodic memory focused on
      one specific component, i.e., the core factual information. The present study
      examines the relevance of a novel episodic paradigm to assess its developmental
      trajectories in a more comprehensive way according to the type of association
      (item-feature, item-location, and item-sequence associations) with measures of
      both objective and subjective recollection. We conducted a behavioral study aimed
      at testing the effects of age in a large sample of 160 children, adolescents, and
      young adults (6-23 years old). We confronted the behavioral data to the neural
      correlates in a subgroup of 30 children using voxel-based morphometry. Behavioral
      data outlined differential developmental trajectories according to the type of
      association, with a continuous increase of factual associative memory efficiency
      until 10 years, a linear increase of performance in spatial associative memory
      that pursues until early adulthood and an abrupt increase in temporal associative
      memory efficiency between 9 and 10. Regarding recollection, measures showed a
      more pronounced enhancement from 9 to 10 years. Hence, behavioral data highlight
      a peculiar period in late childhood (8-10 years old) crucial for the
      developmental time course of episodic memory. Regarding structural data, we found
      that the improvement of associative memory efficiency was related to a decrease
      in gray matter volume in a large cerebral network including the dorsolateral and
      ventrolateral prefrontal cortex (and superior and anterior temporal regions), and
      the hippocampus bilaterally. These data suggest that multimodal integration would
      probably be related to the maturation of temporal regions and modulated by a
      fronto-parietal network. Besides, our findings emphasize the relevance of the
      present paradigm to assess episodic memory especially in the clinical setting. 

PMID- 24098277
TI  - It's time to fear! Interval timing in odor fear conditioning in rats.
AB  - Time perception is crucial to goal attainment in humans and other animals, and
      interval timing also guides fundamental animal behaviors. Accumulating evidence
      has made it clear that in associative learning, temporal relations between events
      are encoded, and a few studies suggest this temporal learning occurs very
      rapidly. Most of these studies, however, have used methodologies that do not
      permit investigating the emergence of this temporal learning. In the present
      study we monitored respiration, ultrasonic vocalization (USV) and freezing
      behavior in rats in order to perform fine-grain analysis of fear responses during
      odor fear conditioning. In this paradigm an initially neutral odor (the
      conditioned stimulus, CS) predicted the arrival of an aversive unconditioned
      stimulus (US, footshock) at a fixed 20-s time interval. We first investigated the
      development of a temporal pattern of responding related to CS-US interval
      duration. The data showed that during acquisition with odor-shock pairings, a
      temporal response pattern of respiration rate was observed. Changing the CS-US
      interval duration from 20-s to 30-s resulted in a shift of the temporal response
      pattern appropriate to the new duration thus demonstrating that the pattern
      reflected the learning of the CS-US interval. A temporal pattern was also
      observed during a retention test 24 h later for both respiration and freezing
      measures, suggesting that the animals had stored the interval duration in long
      term memory. We then investigated the role of intra-amygdalar dopaminergic
      transmission in interval timing. For this purpose, the D1 dopaminergic receptors
      antagonist SCH23390 was infused in the basolateral amygdala before conditioning.
      This resulted in an alteration of timing behavior, as reflected in differential
      temporal patterns between groups observed in a 24 h retention test off drug. The
      present data suggest that D1 receptor dopaminergic transmission within the
      amygdala is involved in temporal processing. 

PMID- 24098279
TI  - Microcognitive science: bridging experiential and neuronal microdynamics.
AB  - Neurophenomenology, as an attempt to combine and mutually enlighten neural and
      experiential descriptions of cognitive processes, has met practical difficulties
      which have limited its implementation into actual research projects. The main
      difficulty seems to be the disparity of the levels of description: while
      neurophenomenology strongly emphasizes the micro-dynamics of experience, at the
      level of brief mental events with very specific content, most neural measures
      have much coarser functional selectivity, because they mix functionally
      heterogeneous neural processes either in space or in time. We propose a new
      starting point for this neurophenomenology, based on (a) the recent development
      of human intra-cerebral EEG (iEEG) research to highlight the neural micro
      dynamics of human cognition, with millimetric and millisecond precision and (b) a
      disciplined access to the experiential micro-dynamics, through specific
      elicitation techniques. This lays the foundation for a microcognitive science,
      the practical implementation of neurophenomenology to combine the neural and
      experiential investigations of human cognition at the subsecond level. 

PMID- 24098280
TI  - Unimodal and multimodal regions for logographic language processing in left
      ventral occipitotemporal cortex.
AB  - The human neocortex appears to contain a dedicated visual word form area (VWFA)
      and an adjacent multimodal (visual/auditory) area. However, these conclusions are
      based on functional magnetic resonance imaging (fMRI) of alphabetic language
      processing, languages that have clear grapheme-to-phoneme correspondence (GPC)
      rules that make it difficult to disassociate visual-specific processing from form
      to-sound mapping. In contrast, the Chinese language has no clear GPC rules.
      Therefore, the current study examined whether native Chinese readers also have
      the same VWFA and multimodal area. Two cross-modal tasks, phonological retrieval
      of visual words and orthographic retrieval of auditory words, were adopted.
      Different task requirements were also applied to explore how different levels of
      cognitive processing modulate activation of putative VWFA-like and multimodal
      like regions. Results showed that the left occipitotemporal sulcus (LOTS)
      responded exclusively to visual inputs and an adjacent region, the left inferior
      temporal gyrus (LITG), showed comparable activation for both visual and auditory
      inputs. Surprisingly, processing levels did not significantly alter activation of
      these two regions. These findings indicated that there are both unimodal and
      multimodal word areas for non-alphabetic language reading, and that activity in
      these two word-specific regions are independent of task demands at the linguistic
      level. 

PMID- 24098278
TI  - Altered neural connectivity in excitatory and inhibitory cortical circuits in
      autism.
AB  - Converging evidence from diverse studies suggests that atypical brain
      connectivity in autism affects in distinct ways short- and long-range cortical
      pathways, disrupting neural communication and the balance of excitation and
      inhibition. This hypothesis is based mostly on functional non-invasive studies
      that show atypical synchronization and connectivity patterns between cortical
      areas in children and adults with autism. Indirect methods to study the course
      and integrity of major brain pathways at low resolution show changes in
      fractional anisotropy (FA) or diffusivity of the white matter in autism. Findings
      in post-mortem brains of adults with autism provide evidence of changes in the
      fine structure of axons below prefrontal cortices, which communicate over short-
      or long-range pathways with other cortices and subcortical structures. Here we
      focus on evidence of cellular and axon features that likely underlie the changes
      in short- and long-range communication in autism. We review recent findings of
      changes in the shape, thickness, and volume of brain areas, cytoarchitecture,
      neuronal morphology, cellular elements, and structural and neurochemical features
      of individual axons in the white matter, where pathology is evident even in gross
      images. We relate cellular and molecular features to imaging and genetic studies
      that highlight a variety of polymorphisms and epigenetic factors that primarily
      affect neurite growth and synapse formation and function in autism. We report
      preliminary findings of changes in autism in the ratio of distinct types of
      inhibitory neurons in prefrontal cortex, known to shape network dynamics and the
      balance of excitation and inhibition. Finally we present a model that synthesizes
      diverse findings by relating them to developmental events, with a goal to
      identify common processes that perturb development in autism and affect neural
      communication, reflected in altered patterns of attention, social interactions,
      and language. 

PMID- 24098282
TI  - Abnormalities of functional brain networks in pathological gambling: a graph
      theoretical approach.
AB  - Functional neuroimaging studies of pathological gambling (PG) demonstrate
      alterations in frontal and subcortical regions of the mesolimbic reward system.
      However, most investigations were performed using tasks involving reward
      processing or executive functions. Little is known about brain network
      abnormalities during task-free resting state in PG. In the present study, graph
      theoretical methods were used to investigate network properties of resting state
      functional magnetic resonance imaging data in PG. We compared 19 patients with PG
      to 19 healthy controls (HCs) using the Graph Analysis Toolbox (GAT). None of the
      examined global metrics differed between groups. At the nodal level, pathological
      gambler showed a reduced clustering coefficient in the left paracingulate cortex
      and the left juxtapositional lobe (supplementary motor area, SMA), reduced local
      efficiency in the left SMA, as well as an increased node betweenness for the left
      and right paracingulate cortex and the left SMA. At an uncorrected threshold
      level, the node betweenness in the left inferior frontal gyrus was decreased and
      increased in the caudate. Additionally, increased functional connectivity between
      fronto-striatal regions and within frontal regions has also been found for the
      gambling patients. These findings suggest that regions associated with the reward
      system demonstrate reduced segregation but enhanced integration while regions
      associated with executive functions demonstrate reduced integration. The present
      study makes evident that PG is also associated with abnormalities in the
      topological network structure of the brain during rest. Since alterations in PG
      cannot be explained by direct effects of abused substances on the brain, these
      findings will be of relevance for understanding functional connectivity in other
      addictive disorders. 

PMID- 24098281
TI  - Imaging structural and functional brain networks in temporal lobe epilepsy.
AB  - Early imaging studies in temporal lobe epilepsy (TLE) focused on the search for
      mesial temporal sclerosis, as its surgical removal results in clinically
      meaningful improvement in about 70% of patients. Nevertheless, a considerable
      subgroup of patients continues to suffer from post-operative seizures. Although
      the reasons for surgical failure are not fully understood, electrophysiological
      and imaging data suggest that anomalies extending beyond the temporal lobe may
      have negative impact on outcome. This hypothesis has revived the concept of human
      epilepsy as a disorder of distributed brain networks. Recent methodological
      advances in non-invasive neuroimaging have led to quantify structural and
      functional networks in vivo. While structural networks can be inferred from
      diffusion MRI tractography and inter-regional covariance patterns of structural
      measures such as cortical thickness, functional connectivity is generally
      computed based on statistical dependencies of neurophysiological time-series,
      measured through functional MRI or electroencephalographic techniques. This
      review considers the application of advanced analytical methods in structural and
      functional connectivity analyses in TLE. We will specifically highlight findings
      from graph-theoretical analysis that allow assessing the topological organization
      of brain networks. These studies have provided compelling evidence that TLE is a
      system disorder with profound alterations in local and distributed networks. In
      addition, there is emerging evidence for the utility of network properties as
      clinical diagnostic markers. Nowadays, a network perspective is considered to be
      essential to the understanding of the development, progression, and management of
      epilepsy. 

PMID- 24098284
TI  - Sodium overload due to a persistent current that attenuates the arrhythmogenic
      potential of a novel LQT3 mutation.
AB  - Long QT syndrome (LQTS) is a congenital abnormality of cardiac repolarization
      that manifests as a prolonged QT interval on 12-lead electrocardiograms (ECGs).
      The syndrome may lead to syncope and sudden death from ventricular
      tachyarrhythmias known as torsades de pointes. An increased persistent Na(+)
      current is known to cause a Ca(2+) overload in case of ischemia for example. Such
      increased Na(+) persistent current is also usually associated to the LQT3
      syndrome. The purpose of this study was to investigate the pathological
      consequences of a novel mutation in a family affected by LQTS. The impact of
      biophysical defects on cellular homeostasis are also investigated. Genomic DNA
      was extracted from blood samples, and a combination of PCR and DNA sequencing of
      several LQTS-linked genes was used to identify mutations. The mutation was
      reproduced in vitro and was characterized using the patch clamp technique and in
      silico quantitative analysis. A novel mutation (Q1476R) was identified on the
      SCN5A gene encoding the cardiac Na(+) channel. Cells expressing the Q1476R
      mutation exhibited biophysical alterations, including a shift of SS inactivation
      and a significant increase in the persistent Na(+) current. The in silico
      analysis confirmed the arrhythmogenic character of the Q1476R mutation. It
      further revealed that the increase in persistent Na(+) current causes a frequency
      dependent Na(+) overload in cardiomyocytes co-expressing WT and mutant Nav1.5
      channels that, in turn, exerts a moderating effect on the lengthening of the
      action potential (AP) duration caused by the mutation. The Q1476R mutation in
      SCN5A results in a three-fold increase in the window current and a persistent
      inward Na(+) current. These biophysical defects may expose the carrier of the
      mutation to arrhythmias that occur preferentially in the patient at rest or
      during tachycardia. However, the Na(+) overload counterbalances the gain-of
      function of the mutation and is beneficial in that it prevents severe arrhythmias
      at intermediate heart rates. 

PMID- 24098283
TI  - Unique catalytic activities and scaffolding of p21 activated kinase-1 in
      cardiovascular signaling.
AB  - P21 activated kinase-1 (Pak1) has diverse functions in mammalian cells. Although
      a large number of phosphoproteins have been designated as Pak1 substrates from in
      vitro studies, emerging evidence has indicated that Pak1 may function as a
      signaling molecule through a unique molecular mechanism - scaffolding. By
      scaffolding, Pak1 delivers signals through an auto-phosphorylation-induced
      conformational change without transfer of a phosphate group to its immediate
      downstream effector(s). Here we review evidence for this regulatory mechanism
      based on structural and functional studies of Pak1 in different cell types and
      research models as well as in vitro biochemical assays. We also discuss the
      implications of Pak1 scaffolding in disease-related signaling processes and the
      potential in cardiovascular drug development. 

PMID- 24098285
TI  - Emerging key roles for P2X receptors in the kidney.
AB  - P2X ionotropic non-selective cation channels are expressed throughout the kidney
      and are activated in a paracrine or autocrine manner following the binding of
      extracellular ATP and related extracellular nucleotides. Whilst there is a wealth
      of literature describing a regulatory role of P2 receptors (P2R) in the kidney,
      there are significantly less data on the regulatory role of P2X receptors (P2XR)
      compared with that described for metabotropic P2Y. Much of the historical
      literature describing a role for P2XR in the kidney has focused heavily on the
      role of P2X1R in the autoregulation of renal blood flow. More recently, however,
      there has been a plethora of manuscripts providing compelling evidence for
      additional roles for P2XR in both kidney health and disease. This review
      summarizes the current evidence for the involvement of P2XR in the regulation of
      renal tubular and vascular function, and highlights the novel data describing
      their putative roles in regulating physiological and pathophysiological processes
      in the kidney. 

PMID- 24098286
TI  - Epigenetic Biomarkers as Predictors and Correlates of Symptom Improvement
      Following Psychotherapy in Combat Veterans with PTSD.
AB  - Epigenetic alterations offer promise as diagnostic or prognostic markers, but it
      is not known whether these measures associate with, or predict, clinical state.
      These questions were addressed in a pilot study with combat veterans with PTSD to
      determine whether cytosine methylation in promoter regions of the glucocorticoid
      related NR3C1 and FKBP51 genes would predict or associate with treatment outcome.
      Veterans with PTSD received prolonged exposure (PE) psychotherapy, yielding
      responders (n = 8), defined by no longer meeting diagnostic criteria for PTSD,
      and non-responders (n = 8). Blood samples were obtained at pre-treatment, after
      12 weeks of psychotherapy (post-treatment), and after a 3-month follow-up.
      Methylation was examined in DNA extracted from lymphocytes. Measures reflecting
      glucocorticoid receptor (GR) activity were also obtained (i.e., plasma and 24 h
      urinary cortisol, plasma ACTH, lymphocyte lysozyme IC50-DEX, and plasma
      neuropeptide-Y). Methylation of the GR gene (NR3C1) exon 1F promoter assessed at
      pre-treatment predicted treatment outcome, but was not significantly altered in
      responders or non-responders at post-treatment or follow-up. In contrast,
      methylation of the FKBP5 gene (FKBP51) exon 1 promoter region did not predict
      treatment response, but decreased in association with recovery. In a subset, a
      corresponding group difference in FKBP5 gene expression was observed, with
      responders showing higher gene expression at post-treatment than non-responders.
      Endocrine markers were also associated with the epigenetic markers. These
      preliminary observations require replication and validation. However, the results
      support research indicating that some glucocorticoid related genes are subject to
      environmental regulation throughout life. Moreover, psychotherapy constitutes a
      form of "environmental regulation" that may alter epigenetic state. Finally, the
      results further suggest that different genes may be associated with prognosis and
      symptom state, respectively. 

PMID- 24098287
TI  - Mind-blanking: when the mind goes away.
AB  - People often feel like their minds and their bodies are in different places. Far
      from an exotic experience, this phenomenon seems to be a ubiquitous facet of
      human life (e.g., Killingsworth and Gilbert, 2010). Many times, people's minds
      seem to go "somewhere else"-attention becomes disconnected from perception, and
      people's minds wander to times and places removed from the current environment
      (e.g., Schooler et al., 2004). At other times, however, people's minds may seem
      to go nowhere at all-they simply disappear. This mental state-mind-blanking-may
      represent an extreme decoupling of perception and attention, one in which
      attention fails to bring any stimuli into conscious awareness. In the present
      research, we outline the properties of mind-blanking, differentiating this mental
      state from other mental states in terms of phenomenological experience,
      behavioral outcomes, and underlying cognitive processes. Seven experiments
      suggest that when the mind seems to disappear, there are times when we have
      simply failed to monitor its whereabouts-and there are times when it is actually
      gone. 

PMID- 24098288
TI  - Both hand position and movement direction modulate visual attention.
AB  - The current study explored effects of continuous hand motion on the allocation of
      visual attention. A concurrent paradigm was used to combine visually concealed
      continuous hand movements with an attentionally demanding letter discrimination
      task. The letter probe appeared contingent upon the moving right hand passing
      through one of six positions. Discrimination responses were then collected via a
      keyboard press with the static left hand. Both the right hand's position and its
      movement direction systematically contributed to participants' visual
      sensitivity. Discrimination performance increased substantially when the right
      hand was distant from, but moving toward the visual probe location (replicating
      the far-hand effect, Festman et al., 2013). However, this effect disappeared when
      the probe appeared close to the static left hand, supporting the view that static
      and dynamic features of both hands combine in modulating pragmatic maps of
      attention. 

PMID- 24098289
TI  - A distributed code for color in natural scenes derived from center-surround
      filtered cone signals.
AB  - In the retina of trichromatic primates, chromatic information is encoded in an
      opponent fashion and transmitted to the lateral geniculate nucleus (LGN) and
      visual cortex via parallel pathways. Chromatic selectivities of neurons in the
      LGN form two separate clusters, corresponding to two classes of cone opponency.
      In the visual cortex, however, the chromatic selectivities are more distributed,
      which is in accordance with a population code for color. Previous studies of cone
      signals in natural scenes typically found opponent codes with chromatic
      selectivities corresponding to two directions in color space. Here we
      investigated how the non-linear spatio-chromatic filtering in the retina
      influences the encoding of color signals. Cone signals were derived from hyper
      spectral images of natural scenes and preprocessed by center-surround filtering
      and rectification, resulting in parallel ON and OFF channels. Independent
      Component Analysis (ICA) on these signals yielded a highly sparse code with basis
      functions that showed spatio-chromatic selectivities. In contrast to previous
      analyses of linear transformations of cone signals, chromatic selectivities were
      not restricted to two main chromatic axes, but were more continuously distributed
      in color space, similar to the population code of color in the early visual
      cortex. Our results indicate that spatio-chromatic processing in the retina leads
      to a more distributed and more efficient code for natural scenes. 

PMID- 24098290
TI  - Time course of electrocortical food-cue responses during cognitive regulation of
      craving.
AB  - In our current obesogenic environment, exposure to visual food-cues can easily
      lead to craving and overeating because short-term, pleasurable effects of food
      intake dominate over the anticipated long-term adverse effects such as weight
      gain and associated health problems. Here we contrasted these two conditions
      during food-cue presentation while acquiring event-related potentials (ERPs) and
      subjective craving ratings. Female participants (n = 25) were presented with
      either high-calorie (HC) or low-calorie (LC) food images under instructions to
      imagine either immediate (NOW) or long-term effects (LATER) of consumption. On
      subjective ratings for HC foods, the LATER perspective reduced cravings as
      compared to the NOW perspective. For LC foods, by contrast, craving increased
      under the LATER perspective. Early ERPs (occipital N1, 150-200 ms) were sensitive
      to food type but not to perspective. Late ERPs (late positive potential, LPP, 350
      550 ms) were larger in the HC-LATER condition than in all other conditions,
      possibly indicating that a cognitive focus on negative long-term consequences
      induced negative arousal. This enhancement for HC-LATER attenuated to the level
      of the LC conditions during the later slow wave (550-3000 ms), but amplitude in
      the HC-NOW condition was larger than in all other conditions, possibly due to a
      delayed appetitive response. Across all conditions, LPP amplitudes were
      positively correlated with self-reported emotional eating. In sum, results reveal
      that regulation effects are secondary to an early attentional analysis of food
      type and dynamically evolve over time. Adopting a long-term perspective on eating
      might promote a healthier food choice across a range of food types. 

PMID- 24098291
TI  - How does emotional wellbeing relate to underachievement in a general population
      sample of young adolescents: a neurocognitive perspective.
AB  - Underachievement in school during early adolescence predicts future economic and
      personal difficulties. Particular neurocognitive skills on the domain of
      executive functions start to mature during adolescence. This fact and the
      physical and psychological changes typical for the transition from childhood to
      adulthood make adolescents vulnerable to emotional problems. The current study
      investigated the relationship between mild emotional problems which are highly
      prevalent among adolescents and underachievement in school, and the role of
      neurocognitive functioning in this relation. This study was conducted in a
      substantial sample of typical developing young adolescents who just made the
      transition to secondary education. Pupils were on average 12.5 years old
      (standard deviation 0.5), and 45% of the included sample were girls. Emotional
      wellbeing was associated with underachievement [Odds ratio (OR) 5.15, 95%
      confidence interval (CI) 3.06-8.68] after adjusting for background variables.
      Self-reported neurocognitive functioning partly explained the relation between
      emotional wellbeing and underachievement (OR 2.22, 95% CI 1.23-3.99), yet,
      emotional wellbeing remained statistically associated with underachievement after
      correcting for additional confounders (OR 1.99, 95% CI 1.08-3.66). The observed
      findings suggest that emotional wellbeing plays an essential role in
      underachievement during the first year of secondary education. 

PMID- 24098292
TI  - Context effects on processing widely deviant sounds in newborn infants.
AB  - Detecting and orienting toward sounds carrying new information is a crucial
      feature of the human brain that supports adaptation to the environment. Rare,
      acoustically widely deviant sounds presented amongst frequent tones elicit large
      event-related brain potentials (ERPs) in neonates. Here we tested whether these
      discriminative ERP responses reflect only the activation of fresh afferent
      neuronal populations (i.e., neuronal circuits not affected by the tones) or they
      also index the processing of contextual mismatch between the rare and the
      frequent sounds. In two separate experiments, we presented sleeping newborns with
      150 different environmental sounds and the same number of white noise bursts.
      Both sounds served either as deviants in an oddball paradigm with the frequent
      standard stimulus a tone (Novel/Noise deviant), or as the standard stimulus with
      the tone as deviant (Novel/Noise standard), or they were delivered alone with the
      same timing as the deviants in the oddball condition (Novel/Noise alone). Whereas
      the ERP responses to noise-deviants elicited similar responses as the same sound
      presented alone, the responses elicited by environmental sounds in the
      corresponding conditions morphologically differed from each other. Thus whereas
      the ERP response to the noise sounds can be explained by the different refractory
      state of stimulus-specific neuronal populations, the ERP response to
      environmental sounds indicated context-sensitive processing. These results
      provide evidence for an innate tendency of context-dependent auditory processing
      as well as a basis for the different developmental trajectories of processing
      acoustical deviance and contextual novelty. 

PMID- 24098293
TI  - When combinatorial processing results in reconceptualization: toward a new
      approach of compositionality.
AB  - Propositional content is often incomplete but comprehenders appear to adjust
      meaning and add unarticulated meaning constituents effortlessly. This happens at
      the propositional level (The baby drank the bottle) but also at the phrasal level
      (the wooden turtle). In two ERP experiments, combinatorial processing was
      investigated in container/content alternations and adjective-noun combination
      transforming an animate entity into a physical object. Experiment 1 revealed that
      container-for-content alternations (The baby drank the bottle) engendered a Late
      Positivity on the critical expression and on the subsequent segment, while
      content-for-container alternations (Chris put the beer on the table) did not
      exert extra costs. In Experiment 2, adjective-noun combinations (the wooden
      turtle) also evoked a Late Positivity on the critical noun. First, the Late
      Positivities are taken to reflect discourse updating demands resulting from
      reference shift from the original denotation to the contextually appropriate
      interpretation (e.g., the reconceptualization form animal to physical object).
      This shift is supported by the linguistic unavailability of the original meaning,
      exemplified by copredication tests. Second, the data reveal that meaning
      alternations differ qualitatively. Some alternations involve (cost-free) meaning
      selection, while others engender processing demands associated with
      reconceptualization. This dissociation thus calls for a new typology of metonymic
      shifts that centers around the status of the involved discourse referents. 

PMID- 24098294
TI  - The added value of eye-tracking in diagnosing dyscalculia: a case study.
AB  - The present study compared eye movements and performance of a 9-year-old girl
      with Developmental Dyscalculia (DD) on a series of number line tasks to those of
      a group of typically developing (TD) children (n = 10), in order to answer the
      question whether eye-tracking data from number line estimation tasks can be a
      useful tool to discriminate between TD children and children with a number
      processing deficit. Quantitative results indicated that the child with
      dyscalculia performed worse on all symbolic number line tasks compared to the
      control group, indicated by a low linear fit (R (2)) and a low accuracy measured
      by mean percent absolute error. In contrast to the control group, her magnitude
      representations seemed to be better represented by a logarithmic than a linear
      fit. Furthermore, qualitative analyses on the data of the child with dyscalculia
      revealed more unidentifiable fixation patterns in the processing of multi-digit
      numbers and more dysfunctional estimation strategy use in one third of the
      estimation trials as opposed to ~10% in the control group. In line with her
      dyscalculia diagnosis, these results confirm the difficulties with spatially
      representing and manipulating numerosities on a number line, resulting in
      inflexible and inadequate estimation or processing strategies. It can be
      concluded from this case study that eye-tracking data can be used to discern
      different number processing and estimation strategies in TD children and children
      with a number processing deficit. Hence, eye-tracking data in combination with
      number line estimation tasks might be a valuable and promising addition to
      current diagnostic measures. 

PMID- 24098295
TI  - EEG-Neurofeedback in psychodynamic treatment of substance dependence.

PMID- 24098296
TI  - The Complex Clinical Issues Involved in an Athlete's Decision to Retire from
      Collision Sport Due to Multiple Concussions: A Case Study of a Professional
      Athlete.
AB  - The issue of retirement from athletic participation due to repetitive concussive
      injuries remains controversial. The complexity of providing recommendations to
      elite athletes is highlighted by the prospect that offering inappropriate advice
      may foreseeably lead to engagement in a medico-legal challenge. Currently no
      evidenced-based, scientifically validated guidelines for forming the basis of
      such a decision exist. The current paper discusses the complexities of this
      challenge in addition to presenting a case study of a professional athlete. A
      number of central issues to consider when discussing athlete retirement revolve
      around the player's medical and concussion histories, the current clinical
      profile, the athlete's long-term life goals, and understanding of the potential
      long-term risks. Ensuring that thorough investigations of all possible
      differential diagnosis, that may explain the presenting symptoms, are conducted
      is also essential. Discussion pertaining to recommendations for guiding the
      clinical approach to the retirement issue for athletes with a history of multiple
      concussions is presented. 

PMID- 24098297
TI  - Incidence, clinical presentation, and antimicrobial resistance trends in
      Salmonella and Shigella infections from children in Yucatan, Mexico.
AB  - BACKGROUND: Salmonella and Shigella cause significant morbidity and mortality
      among children worldwide. Increased antimicrobial resistance results in greater
      burden of disease. MATERIALS AND METHODS: From 2005 to 2011, Salmonella and
      Shigella isolates collected from ill children at a major hospital in Yucatan,
      Mexico, were subjected to serotyping and antimicrobial susceptibility testing by
      disk diffusion and agar dilution. The identification of bla CTX, bla CMY, bla
      SHV, bla TEM, and bla OXA and qnr resistance genes was conducted by PCR and
      sequencing. RESULTS: Among 2344 children with acute gastroenteritis,
      salmonellosis decreased from 17.7% in 2005 to 11.2% in 2011 (p < 0.001). In
      contrast, shigellosis increased from 8.3% in 2010 to 12.1% in 2011. Compared to
      children with Salmonella, those with Shigella had significantly more bloody
      stools (59 vs 36%, p < 0.001), dehydration (27 vs 15%, p = 0.031), and seizures
      (11 vs 3%, p = 0.03). In Salmonella (n = 365), there was a significant decrease
      in resistance to ampicillin (43 to 16%, p < 0.001), trimethoprim-sulfamethoxazole
      (44 to 26%, p = 0.014), and extended-spectrum cephalosporins (27 to 10%, p =
      0.009). Reduced susceptibility to ciprofloxacin in Salmonella rose from 30 to 41%
      (p < 0.001). All ceftriaxone-resistant isolates harbored the bla CMY-2 gene. qnr
      genes were found in 42 (36%) of the 117 Salmonella isolates with a ciprofloxacin
      MIC >= 0.125 MUg/ml. Four were qnrA1 and 38 were qnrB19. Resistance to ampicillin
      (40%) and trimethoprim-sulfamethoxazole (58%) was common in Shigella (n = 218),
      but isolates remained fully susceptible to ceftriaxone and ciprofloxacin.
      CONCLUSION: Illness from Salmonella has decreased while severe Shigella
      infections have increased among children with gastroenteritis in the Yucatan
      Peninsula. While Shigella resistance to clinically important antibiotics remained
      unchanged, resistance to most of these, except ciprofloxacin, declined in
      Salmonella. bla CMY-2 and qnr genes are common in Salmonella isolates.

PMID- 24098298
TI  - A novel and simple method for generation of human dendritic cells from
      unfractionated peripheral blood mononuclear cells within 2 days: its application
      for induction of HIV-1-reactive CD4(+) T cells in the hu-PBL SCID mice.
AB  - Because dendritic cells (DCs) play a critical role in the regulation of adaptive
      immune responses, they have been ideal candidates for cell-based immunotherapy of
      cancers and infections in humans. Generally, monocyte-derived DCs (MDDCs) were
      generated from purified monocytes by multiple steps of time-consuming physical
      manipulations for an extended period cultivation. In this study, we developed a
      novel, simple and rapid method for the generation of type-1 helper T cell (Th1)
      stimulating human DCs directly from bulk peripheral blood mononuclear cells
      (PBMCs). PBMCs were cultivated in the presence of 20 ng/ml of granulocyte
      macrophage colony-stimulating factor, 20 ng/ml of interleukin-4 (IL-4) and 1,000
      U/ml of interferon-beta for 24 h followed by 24 h maturation with a cytokine
      cocktail containing 10 ng/ml of tumor necrosis factor-alpha (TNF-alpha), 10 ng/ml
      of IL-1beta and 1 MUg/ml of prostaglandin E2. The phenotype and biological
      activity of these new DCs for induction of allogeneic T cell proliferation and
      cytokine production were comparable to those of the MDDCs. Importantly, these new
      DCs pulsed with inactivated HIV-1 could generated HIV-1-reactive CD4(+) T cell
      responses in humanized mice reconstituted with autologous PBMCs from HIV-1
      negative donors. This simple and quick method for generation of functional DCs
      will be useful for future studies on DC-mediated immunotherapies. 

PMID- 24098299
TI  - Virus-induced exacerbations in asthma and COPD.
AB  - Chronic obstructive pulmonary disease (COPD) is characterized by chronic airway
      inflammation and/or airflow limitation due to pulmonary emphysema. Chronic
      bronchitis, pulmonary emphysema, and bronchial asthma may all be associated with
      airflow limitation; therefore, exacerbation of asthma may be associated with the
      pathophysiology of COPD. Furthermore, recent studies have suggested that the
      exacerbation of asthma, namely virus-induced asthma, may be associated with a
      wide variety of respiratory viruses. COPD and asthma have different underlying
      pathophysiological processes and thus require individual therapies. Exacerbation
      of both COPD and asthma, which are basically defined and diagnosed by clinical
      symptoms, is associated with a rapid decline in lung function and increased
      mortality. Similar pathogens, including human rhinovirus, respiratory syncytial
      virus, influenza virus, parainfluenza virus, and coronavirus, are also frequently
      detected during exacerbation of asthma and/or COPD. Immune response to
      respiratory viral infections, which may be related to the severity of
      exacerbation in each disease, varies in patients with both COPD and asthma. In
      this regard, it is crucial to recognize and understand both the similarities and
      differences of clinical features in patients with COPD and/or asthma associated
      with respiratory viral infections, especially in the exacerbative stage. In
      relation to definition, epidemiology, and pathophysiology, this review aims to
      summarize current knowledge concerning exacerbation of both COPD and asthma by
      focusing on the clinical significance of associated respiratory virus infections.

PMID- 24098300
TI  - "Model t" cells: a time-tested vehicle for gene therapy.
AB  - T lymphocytes first carried foreign genes safely into humans over two decades
      ago. Since these pioneering studies, scientific techniques to better understand
      the genomic landscape of cells has directly led to a more sophisticated
      appreciation of the diversity, functional complexity, and therapeutic potential
      of T cells. Through the use of mouse models, we now know the function of the many
      genes that are critical for T cells to recognize foreign, mutated, or self
      antigens and the factors responsible for the lineage diversification of T cells
      that lead to inhibitory or stimulatory immune responses. This knowledge combined
      with well-established modalities to introduce genes into T cells allows for the
      design of effector and memory CD8 and CD4 T lymphocytes specific for viral,
      fungal, bacterial, parasitic, and tumor-antigens and to design regulatory
      lymphocytes specific for the self-antigens responsible for autoimmune and
      inflammatory diseases. Here, I review strategies for designing the ideal T cell
      by introducing genes controlling (1) the secretion of cytokines/chemokines and
      their receptors, (2) T-cell receptor specificity, (3) chimeric-antigen receptors
      that enable for the recognition of surface antigens in an MHC-independent
      fashion, (4) co-stimulatory/inhibitory surface molecules, and (5) disease
      defining single-gene factors. 

PMID- 24098301
TI  - Influence of transplant size on the above- and below-ground performance of four
      contrasting field-grown lettuce cultivars.
AB  - BACKGROUND AND AIMS: Modern lettuce cultivars underperform under conditions of
      variable temporal and spatial resource availability, common in organic or low
      input production systems. Information is scarce on the impact of below-ground
      traits on such resource acquisition and performance of field-grown lettuce;
      exploring genetic variation in such traits might contribute to strategies to
      select for robust cultivars, i.e., cultivars that perform well in the field, even
      under stress. METHODS: To investigate the impact of below-ground (root
      development and resource capture) on above-ground (shoot weight, leaf area)
      traits, different combinations of shoot and root growth were created using
      transplants of different sizes in three field experiments. Genetic variation in
      morphological and physiological below- and above-ground responses to different
      types of transplant shocks was assessed using four cultivars. RESULTS:
      Transplanting over-developed seedlings did not affect final yield of any of the
      four cultivars. Small transplant size persistently impacted growth and delayed
      maturity. The cultivars with overall larger root weights and rooting depth,
      "Matilda" and "Pronto," displayed a slightly higher growth rate in the linear
      phase leading to better yields than "Mariska" which had a smaller root system and
      a slower linear growth despite a higher maximal exponential growth rate.
      "Nadine," which had the highest physiological nitrogen-use efficiency (g dry
      matter produced per g N accumulated in the head) among the four cultivars used in
      these trials, gave most stable yields over seasons and trial locations.
      CONCLUSIONS: Robustness was conferred by a large root system exploring deep soil
      layers. Additional root proliferation generally correlates with improved nitrate
      capture in a soil layer and cultivars with a larger root system may therefore
      perform better in harsh environmental conditions; increased nitrogen use
      efficiency can also confer robustness at low cost for the plant, and secure
      stable yields under a wide range of growing conditions.

PMID- 24098302
TI  - Engineering the Oryza sativa cell wall with rice NAC transcription factors
      regulating secondary wall formation.
AB  - Plant tissues that require structural rigidity synthesize a thick, strong
      secondary cell wall of lignin, cellulose and hemicelluloses in a complicated
      bridged structure. Master regulators of secondary wall synthesis were identified
      in dicots, and orthologs of these regulators have been identified in monocots,
      but regulation of secondary cell wall formation in monocots has not been
      extensively studied. Here we demonstrate that the rice transcription factors
      SECONDARY WALL NAC DOMAIN PROTEINs (SWNs) can regulate secondary wall formation
      in rice (Oryza sativa) and are potentially useful for engineering the monocot
      cell wall. The OsSWN1 promoter is highly active in sclerenchymatous cells of the
      leaf blade and less active in xylem cells. By contrast, the OsSWN2 promoter is
      highly active in xylem cells and less active in sclerenchymatous cells. OsSWN2
      splicing variants encode two proteins; the shorter protein (OsSWN2S) has very low
      transcriptional activation ability, but the longer protein (OsSWN2L) and OsSWN1
      have strong transcriptional activation ability. In rice, expression of an OsSWN2S
      chimeric repressor, driven by the OsSWN2 promoter, resulted in stunted growth and
      para-wilting (leaf rolling and browning under normal water conditions) due to
      impaired vascular vessels. The same OsSWN2S chimeric repressor, driven by the
      OsSWN1 promoter, caused a reduction of cell wall thickening in sclerenchymatous
      cells, a drooping leaf phenotype, reduced lignin and xylose contents and
      increased digestibility as forage. These data suggest that OsSWNs regulate
      secondary wall formation in rice and manipulation of OsSWNs may enable
      improvements in monocotyledonous crops for forage or biofuel applications. 

PMID- 24098303
TI  - Nitrogen modulation of legume root architecture signaling pathways involves
      phytohormones and small regulatory molecules.
AB  - Nitrogen, particularly nitrate is an important yield determinant for crops.
      However, current agricultural practice with excessive fertilizer usage has
      detrimental effects on the environment. Therefore, legumes have been suggested as
      a sustainable alternative for replenishing soil nitrogen. Legumes can uniquely
      form nitrogen-fixing nodules through symbiotic interaction with specialized soil
      bacteria. Legumes possess a highly plastic root system which modulates its
      architecture according to the nitrogen availability in the soil. Understanding
      how legumes regulate root development in response to nitrogen availability is an
      important step to improving root architecture. The nitrogen-mediated root
      development pathway starts with sensing soil nitrogen level followed by
      subsequent signal transduction pathways involving phytohormones, microRNAs and
      regulatory peptides that collectively modulate the growth and shape of the root
      system. This review focuses on the current understanding of nitrogen-mediated
      legume root architecture including local and systemic regulations by different N
      sources and the modulations by phytohormones and small regulatory molecules. 

PMID- 24098304
TI  - A more complete picture of metal hyperaccumulation through next-generation
      sequencing technologies.
AB  - The mechanistic understanding of metal hyperaccumulation has benefitted immensely
      from the use of molecular genetics tools developed for Arabidopsis thaliana. The
      revolution in DNA sequencing will enable even greater strides in the near future,
      this time not restricted to the family Brassicaceae. Reference genomes are within
      reach for many ecologically interesting species including heterozygous
      outbreeders. They will allow deep RNA-seq transcriptome studies and the re
      sequencing of contrasting individuals to unravel the genetic basis of phenotypic
      variation. Cell-type specific transcriptome analyses, which will be essential for
      the dissection of metal translocation pathways in hyperaccumulators, can be
      achieved through the combination of RNA-seq and translatome approaches.
      Affordable high-resolution genotyping of many individuals enables the elucidation
      of quantitative trait loci in intra- and interspecific crosses as well as through
      genome-wide association mapping across large panels of accessions. Furthermore,
      genome-wide scans have the power to detect loci under recent selection. Together
      these approaches will lead to a detailed understanding of the evolutionary path
      towards the emergence of hyperaccumulation traits. 

PMID- 24098305
TI  - Combining genetic association study designs: a GWAS case study.
AB  - Genome-wide association studies (GWAS) explore the relationship between genome
      variability and disease susceptibility with either population- or family-based
      data. Here, we have evaluated the utility of combining population- and family
      based statistical association tests and have proposed a method for reducing the
      burden of multiple testing. Unrelated singleton and parent-offspring trio cases
      and controls from the Genetics of Kidneys in Diabetes (GoKinD) study were
      analyzed for genetic association with diabetic nephropathy (DN) in type 1
      diabetics (T1D). The Cochran-Armitage test for trend and the family-based
      association test were employed using either unrelated cases and controls or
      trios, respectively. In addition to combining single nucleotide polymorphism
      (SNP) p-values across these tests via Fisher's method, we employed a novel
      screening approach to rank SNPs based on conditional power for more efficient
      testing. Using either the population-based or family-based subset alone
      predictably limited resolution to detect DN SNPs. For 384,197 SNPs passing
      quality control (QC), none achieved strict genome-wide significance (1.4 * 10(
      7)) using 1171 singletons (577/594 cases/controls) or 1738 pooled singletons and
      offspring probands (841/897). Similarly, none of the 352,004 SNPs passing QC in
      567 family trios (264/303 case/control proband trios) reached genome-wide
      significance. Testing the top 10 SNPs ranked using aggregated conditional power
      resulted in two SNPs reaching genome-wide significance, rs11645147 on chromosome
      16 (p = 1.74 * 10(-4) < 0.05/10 = 0.005) and rs7866522 on chromosome 9 (p =
      0.0033). Efficient usage of mixed designs incorporating both unrelated and family
      based data may help to uncover associations otherwise difficult to detect in the
      presence of massive multiple testing corrections. Capitalizing on the strengths
      of both types while using screening approaches may be useful especially in light
      of large-scale, next-generation sequencing and rare variant studies. 

PMID- 24098306
TI  - Introducing an optimal liver allocation system for liver cirrhosis patients.
AB  - BACKGROUND: Liver transplantation (LT) is the only treatment option for patients
      with advanced liver disease. Currently, liver donation to these patients,
      considering priorities, is based on the Model for End-Stage Liver Disease (MELD).
      MELD score is a tool for predicting the risk of mortality in patients with
      advanced liver disease. However, few studies have so far been conducted in Iran
      on the efficacy of MELD score of these patients. OBJECTIVES: This study reviews
      the present status of the MELD score and introduces a new model for optimal
      prediction of the risk of mortality in Iranian patients with advanced liver
      disease. PATIENTS AND METHODS: Data required were collected from 305 patients
      with advanced liver disease who enrolled in a waiting list (WL) in Imam Khomeini
      Hospital from May 2008 to May 2009. All of the patients were followed up for at
      least 3 years until they died or underwent LT. Cox regression analysis was
      applied to select the factors affecting their mortality. Survival curves were
      plotted. Wilcoxson test and receiver operating characteristics curves for
      survival predictive model were used to compare the scores. All calculations were
      performed with the SPSS (version 13.0) and R softwares. RESULTS: During the
      study, 71 (23.3%) patients died due to liver cirrhosis and 43 (14.1%) underwent
      LT. Viral Hepatitis (43.7%) is the most common cause of end-stage liver disease
      among Iranian patients. A new model (NMELD) was proposed with the use of the
      natural logarithms of two blood serum variables (total bilirubin and albumin) and
      the patients' age (year) by applying the Cox model: NMELD = 10 * (0.736 * ln
      (bilirubin) - 1.312 * ln (albumin) + 0.025 * age + 1.776). CONCLUSIONS: The
      results of the Wilcoxon test showed that there is a significant difference
      between the usual MELD and our proposed NMELD scores (P < 0.001). Receiver
      operating characteristics curve for survival predictive model indicated that the
      NMELD score is more efficient compared with the MELD score in predicting the risk
      of mortality. Since serum creatinine was not significant in NMELD score, further
      studies to clarify this issue are suggested.

PMID- 24098307
TI  - A new subtype of hepatitis C virus genotype 3: analysis of available evidence.
AB  - BACKGROUND: Hepatitis C virus (HCV) is one of the leading causes of chronic liver
      disease. Seven genotypes and more than 80 subtypes have been identified for HCV
      so far. To date, 10 subtypes (3a to 3i; and 3k) of HCV genotype 3 have been
      identified. In 2006, two HCV isolates were reported from Iran that belonged to a
      new subtype of genotype 3. However, considering the consensus proposal for HCV
      genotype nomenclature, the available sequences of the new subtype did not
      correspond to the regions that are required to be analyzed prior to subtype
      assignment. During a study on the molecular epidemiology of HCV in Iran, an HCV
      isolate (FSM165) which seemed to belong to a new subtype of genotype 3 was
      obtained from a patient residing in Tehran, Iran. OBJECTIVES: The aim of this
      study was to assess the relatedness of isolate FM165 together with several
      sequences retrieved from the database to the new HCV-3 subtype reported from Iran
      in 2006. MATERIALS AND METHODS: Various parts of the genome including the core/E1
      region and two segments of the NS5B region were amplified and sequenced for
      isolate FSM165. Furthermore, using the Basic Local Alignment Search Tool (BLAST),
      the HCV database was searched for sequences that had a high level of similarity
      with sequences of FSM165 isolate and such sequences were retrieved from the
      database. To investigate the relatedness of isolate FSM165 and also the retrieved
      sequences to a new HCV-3 subtype reported previously, phylogenetic analyses were
      performed using the Kimura two-parameter model and the neighbor joining method.
      RESULTS: Phylogenetic analysis of the partial NS5B region demonstrated the
      relatedness of isolate FSM165 to the new subtype reported from Iran in 2006.
      Moreover, some core/E1 and NS5B sequences that had a high level of similarity
      with FSM165 isolate were found through searching the HCV database. These
      sequences were previously either misclassified or could not be accurately
      classified. Phylogenetic analyses showed that all of the described sequences
      belonged to the new subtype of HCV genotype 3. CONCLUSIONS: Data suggests that
      the new subtype has a vast geographical distribution in Iran. The core/E1 and the
      NS5B sequences described in this paper can be used as references for the new HCV
      3 subtype in future studies.

PMID- 24098308
TI  - Prevalence of hepatitis delta virus (HDV) infection in chronic hepatitis B
      patients with unusual clinical pictures.
AB  - BACKGROUND: Probably 5% of the HBV carriers have HDV super infection. The risk of
      fulminant hepatitis, cirrhosis and hepatocellular carcinoma is higher in
      superinfection than the settings when HBV is alone. OBJECTIVES: The aim of this
      study was to evaluate the prevalence of HDV in Iranian HBV isolates and to
      compare their clinical and virological pictures as well as their HDV genetic
      variations with other worldwide isolates. PATIENTS AND METHODS: 81 carriers with
      positive results for HBsAg with upper limit ranges of ALT and low or undetectable
      levels of HBV viral load who did not respond to HBV therapy were selected. After
      RT amplification of HDV Delta antigen, direct sequencing and phylogenetic study
      were performed to explore the genotype(s) and nucleotide/amino acid variations.
      RESULTS: 12 (14.8%) patients had positive results for both HDV RNA and anti-HDV.
      The mean ALT level was higher in HDV positive patients (75.9 U/ML) than HBV-mono
      infected individuals; however, the mean HBV viral load was lower in coinfected
      patients than HBV-mono-infected patients. Phylogenetically, genotype I was the
      only detected genotype, and the most closely related isolates were of Turkish,
      Italian and Mongolian origin. Within the delta Ag, there were 326 nucleotide
      mutations, of which 111 and 215 were silent and missense, respectively. The total
      number of amino acid substitution was 148; most were located in known
      functional/epitopic domains. There was no correlation between the numbers of
      amino acid mutations, with clinical, virological status of the patients.
      CONCLUSIONS: HDV should be suspected in HBV carriers with unusual clinical and
      virological pictures. Relatedness of Iranian HDV isolates to Italian and Turkish
      sequences proposed a common Caucasian origin for the distribution of HDV genotype
      I in this ethnic group.

PMID- 24098309
TI  - Prevalence and risk factors for obesity after liver transplantation: a single
      center experience.
AB  - BACKGROUND: The study of weight gain after transplantation and its associated
      factors is necessary to propose strategies to prevent and treat this problem.
      OBJECTIVES: This study aims to investigate factors affecting the development of
      obesity after liver transplantation (LTx). PATIENTS AND METHODS: Medical records
      of 343 liver transplantation cases, which were followed between January 2001 and
      January 2010 at Dokuz Eylul University, were retrospectively analyzed. Patient
      pre-liver transplantation height, body weight, body mass index (BMI)
      measurements, as well as changes in body weight at the beginning, 6 months, 12
      months, and 5 years post-transplantation were observed. BMI measurements with
      records of immunosuppressive therapies were obtained. RESULTS: The study was
      carried out with the records of 226 patients. 151 patients (66.8%) were male; 75
      (33.2%) were female. The mean age was 46.19 +/- 10.2 years. 123 of these liver
      transplants were performed from living donors, while 103 were from cadaveric
      donors. The causes of liver transplantation were hepatitis D virus (HDV)
      infection (28%), hepatitis B virus (HBV) infection (24%), hepatitis C virus (HCV)
      infection (24%), alcoholic liver disease (9%), cryptogenic liver disease (9%),
      autoimmune hepatitis (4%), and other (2%). In this study, the prevalence of
      obesity was 21% at the end of the second year, decreasing to 14% by the end of
      the fifth year. The mean BMI gradually increased during the follow-ups, reaching
      25.1 kg/m2 and 26 kg/m2 six months after liver transplantation and at the end of
      the first year, respectively (P < 0.002). Obesity developed in 18.2% of post
      transplant patients who were receiving a calcineurin inhibitor (CNI). Regarding
      the development of obesity after transplantation, no statistically significant
      difference was found between patients using cyclosporine (CsA) and tacrolimus
      (TAC) (P = 0.07). Six months after liver transplantation, the mean body weight
      gain in the groups receiving steroids and not receiving steroids were 4.71 kg and
      2.7 kg, respectively (P = 0.03). In the post-transplant period, there was no
      significant difference in patients who had received TAC and CsA for development
      of diabetes mellitus (DM), hypertension (HT), or hyperlipidemia (HL) (P = 0.30).
      CONCLUSIONS: Obesity prevalence before and after liver transplantation was
      comparable. Education of obese patients prior to surgery and recommendation of
      medical nutrition therapy should be appropriate. Similar medical care for the non
      obese subjects could prevent increase in obesity prevalence. Non-corticosteroid
      immunosuppressive agents had no significant effect on the development of weight
      gain and obesity. Avoiding the use of long-term steroid therapy and obesity
      education are the key measures for preventing obesity after liver
      transplantation.

PMID- 24098310
TI  - Diagnostic segregation of human brain tumours using Fourier-transform infrared
      and/or Raman spectroscopy coupled with discriminant analysis.
AB  - The most common initial treatment received by patients with a brain tumour is
      surgical removal of the growth. Precise histopathological diagnosis of brain
      tumours is to some extent subjective. Furthermore, currently available diagnostic
      imaging techniques to delineate the excision border during cytoreductive surgery
      lack the required spatial precision to aid surgeons. We set out to determine
      whether infrared (IR) and/or Raman spectroscopy combined with multivariate
      analysis could be applied to discriminate between normal brain tissue and
      different tumour types (meningioma, glioma and brain metastasis) based on the
      unique spectral "fingerprints" of their biochemical composition. Formalin-fixed
      paraffin-embedded tissue blocks of normal brain and different brain tumours were
      de-waxed, mounted on low-E slides and desiccated before being analyzed using
      attenuated total reflection Fourier-transform IR (ATR-FTIR) and Raman
      spectroscopy. ATR-FTIR spectroscopy showed a clear segregation between normal and
      different tumour subtypes. Discrimination of tumour classes was also apparent
      with Raman spectroscopy. Further analysis of spectral data revealed changes in
      brain biochemical structure associated with different tumours. Decreased
      tentatively-assigned lipid-to-protein ratio was associated with increased tumour
      progression. Alteration in cholesterol esters-to-phenylalanine ratio was evident
      in grade IV glioma and metastatic tumours. The current study indicates that IR
      and/or Raman spectroscopy have the potential to provide a novel diagnostic
      approach in the accurate diagnosis of brain tumours and have potential for
      application in intra-operative diagnosis.

PMID- 24098311
TI  - PROBING alphaIIbbeta3: LIGAND INTERACTIONS BY DYNAMIC FORCE SPECTROSCOPY AND
      SURFACE PLASMON RESONANCE.
AB  - The interaction between platelet integrin alphaIIbbeta3 and fibrin(ogen) plays a
      key role in blood clot formation and stability. Integrin antagonists, a class of
      pharmaceuticals used to prevent and treat cardiovascular disease, are designed to
      competitively interfere with this process. However, the energetics of the
      integrin-drug binding are not fully understood, potentially hampering further
      development of this class of pharmaceuticals. We integrated dynamic force
      spectroscopy (DFS) and surface plasmon resonance (SPR) to probe the energetics of
      complex formation between alphaIIbbeta3 and cHarGD, a cyclic peptide integrin
      antagonist. Analysis of alphaIIbbeta3:cHarGD DFS rupture force data at pulling
      rates of 14 000 pN/s, 42 000 pN/s and 70 000 pN/s yielded koff = 0.02-0.09 s-1, a
      dissociation energy barrier [Formula: see text] = 22-29 kJ/mol, and a potential
      well width x-1 = 0.5-0.8 nm. SPR kinetic data yielded an association rate
      constant kon = 7 * 103 L/mol-s and a dissociation rate constant koff = 10-2 s-1,
      followed by a slower stabilization step (tau ~ 400 s). Both DFS and SPR detected
      minimal interactions between alphaIIbbeta3 and cHarGA demonstrating a key role
      for electrostatic interactions between the ligand aspartate and the integrin
      metal ion-dependent adhesion site (MIDAS). Our work provides new insights into
      the energy landscape of alphaIIbbeta3's interactions with pharmacological and
      physiological ligands.

PMID- 24098312
TI  - Informed Consent for Web Paradata Use.
AB  - Survey researchers are making increasing use of paradata - such as keystrokes,
      clicks, and timestamps - to evaluate and improve survey instruments but also to
      understand respondents and how they answer surveys. Since the introduction of
      paradata, researchers have been asking whether and how respondents should be
      informed about the capture and use of their paradata while completing a survey.
      In a series of three vignette-based experiments, we examine alternative ways of
      informing respondents about capture of paradata and seeking consent for their
      use. In all three experiments, any mention of paradata lowers stated willingness
      to participate in the hypothetical surveys. Even the condition where respondents
      were asked to consent to the use of paradata at the end of an actual survey
      resulted in a significant proportion declining. Our research shows that requiring
      such explicit consent may reduce survey participation without adequately
      informing survey respondents about what paradata are and why they are being used.

PMID- 24098314
TI  - Attitudes Toward Fruit and Vegetable Consumption and Farmers' Market Usage Among
      Low-Income North Carolinians.
AB  - Low fruit and vegetable (F&V) consumption is associated with higher rates of
      obesity and chronic disease among low-income individuals. Understanding attitudes
      towards F&V consumption and addressing policy and environmental changes could
      help improve diet and reduce disease risk. A survey of North Carolinians
      receiving government assistance was used to describe benefits, barriers, and
      facilitators of eating F&V and shopping at farmers' markets in this population. A
      total of 341 eligible individuals from 14 counties completed the survey. The most
      commonly cited barriers to eating F&V were cost (26.4%) and not having time to
      prepare F&V (7.3%). Facilitators included access to affordable locally grown F&V
      (13.5%) and knowledge to quickly and easily prepare F&V (13.2%). Among people who
      did not use farmers' markets, common barriers to shopping there were not being
      able to use food assistance program benefits (35.3%) and not knowing of a
      farmers' market in their area (28.8%); common facilitators included
      transportation (24.8%) and having more information about farmers' market hours
      (22.9%). In addition to breaking down structural/environmental barriers to
      farmers' market usage, there is a need to disseminate promotional information
      about farmers' markets, including hours, location, and accepted forms of payment.

PMID- 24098313
TI  - Therapeutic antibodies in stroke.
AB  - Immunotherapy represents an active area of biomedical research to treat cancer,
      autoimmune diseases, and neurodegenerative disorders. In stroke, recanalization
      therapy is effective in reducing brain tissue damage after acute ischemic stroke.
      However, the narrow time window restricts its application for the majority of
      stroke patients. There is an urgent need to develop adjuvant therapies such as
      immunotherapy, stem cell replacement, and neuroprotective drugs. A number of
      molecules have been targeted for immunotherapy in stroke management, including
      myelin-associated proteins and their receptors, N-methyl-d-aspartic acid
      receptors, cytokines, and cell adhesion molecules. Both active vaccination and
      passive antibodies were tested in animal models of acute ischemic stroke.
      However, the mechanisms underlying the efficacy of immunotherapy are different
      for each target protein. Blocking myelin-associated proteins may enhance
      neuroplasticity, whereas blocking adhesion molecules may yield neuroprotection by
      suppressing the immune response after stroke. Although results from animal
      studies are encouraging, clinical trials using therapeutic antibodies failed to
      improve stroke outcome due to severe side effects. It remains a challenge to
      generate specific therapeutic antibodies with minimal side effects on other
      organs and systems. 

PMID- 24098320
TI  - Elemental markers in elasmobranchs: effects of environmental history and growth
      on vertebral chemistry.
AB  - Differences in the chemical composition of calcified skeletal structures (e.g.
      shells, otoliths) have proven useful for reconstructing the environmental history
      of many marine species. However, the extent to which ambient environmental
      conditions can be inferred from the elemental signatures within the vertebrae of
      elasmobranchs (sharks, skates, rays) has not been evaluated. To assess the
      relationship between water and vertebral elemental composition, we conducted two
      laboratory studies using round stingrays, Urobatis halleri, as a model species.
      First, we examined the effects of temperature (16 degrees , 18 degrees , 24
      degrees C) on vertebral elemental incorporation (Li/Ca, Mg/Ca, Mn/Ca, Zn/Ca,
      Sr/Ca, Ba/Ca). Second, we tested the relationship between water and subsequent
      vertebral elemental composition by manipulating dissolved barium concentrations
      (1x, 3x, 6x). We also evaluated the influence of natural variation in growth rate
      on elemental incorporation for both experiments. Finally, we examined the
      accuracy of classifying individuals to known environmental histories (temperature
      and barium treatments) using vertebral elemental composition. Temperature had
      strong, negative effects on the uptake of magnesium (DMg) and barium (DBa) and
      positively influenced manganese (DMn) incorporation. Temperature-dependent
      responses were not observed for lithium and strontium. Vertebral Ba/Ca was
      positively correlated with ambient Ba/Ca. Partition coefficients (DBa) revealed
      increased discrimination of barium in response to increased dissolved barium
      concentrations. There were no significant relationships between elemental
      incorporation and somatic growth or vertebral precipitation rates for any
      elements except Zn. Relationships between somatic growth rate and DZn were,
      however, inconsistent and inconclusive. Variation in the vertebral elemental
      signatures of U. halleri reliably distinguished individual rays from each
      treatment based on temperature (85%) and Ba exposure (96%) history. These results
      support the assumption that vertebral elemental composition reflects the
      environmental conditions during deposition and validates the use of vertebral
      elemental signatures as natural markers in an elasmobranch. Vertebral elemental
      analysis is a promising tool for the study of elasmobranch population structure,
      movement, and habitat use. 

PMID- 24098321
TI  - A genome-wide investigation of copy number variation in patients with sporadic
      brain arteriovenous malformation.
AB  - BACKGROUND: Brain arteriovenous malformations (BAVM) are clusters of abnormal
      blood vessels, with shunting of blood from the arterial to venous circulation and
      a high risk of rupture and intracranial hemorrhage. Most BAVMs are sporadic, but
      also occur in patients with Hereditary Hemorrhagic Telangiectasia, a Mendelian
      disorder caused by mutations in genes in the transforming growth factor beta
      (TGFbeta) signaling pathway. METHODS: To investigate whether copy number
      variations (CNVs) contribute to risk of sporadic BAVM, we performed a genome-wide
      association study in 371 sporadic BAVM cases and 563 healthy controls, all
      Caucasian. Cases and controls were genotyped using the Affymetrix 6.0 array. CNVs
      were called using the PennCNV and Birdsuite algorithms and analyzed via segment
      based and gene-based approaches. Common and rare CNVs were evaluated for
      association with BAVM. RESULTS: A CNV region on 1p36.13, containing the
      neuroblastoma breakpoint family, member 1 gene (NBPF1), was significantly
      enriched with duplications in BAVM cases compared to controls (P = 2.2*10(-9));
      NBPF1 was also significantly associated with BAVM in gene-based analysis using
      both PennCNV and Birdsuite. We experimentally validated the 1p36.13 duplication;
      however, the association did not replicate in an independent cohort of 184
      sporadic BAVM cases and 182 controls (OR = 0.81, P = 0.8). Rare CNV analysis did
      not identify genes significantly associated with BAVM. CONCLUSION: We did not
      identify common CNVs associated with sporadic BAVM that replicated in an
      independent cohort. Replication in larger cohorts is required to elucidate the
      possible role of common or rare CNVs in BAVM pathogenesis.

PMID- 24098322
TI  - MiRNA-181a regulates adipogenesis by targeting tumor necrosis factor-alpha (TNF
      alpha) in the porcine model.
AB  - Adipogenesis is tightly regulated by altering gene expression, and TNF-alpha is a
      multifunctional cytokine that plays an important role in regulating lipogenesis.
      MicroRNAs are strong post-transcriptional regulators of cell differentiation. In
      our previous work, we found high expression of miR-181a in a fat-rich pig breed.
      Using bioinformatic analysis, miR-181a was identified as a potential regulator of
      TNF-alpha. Here, we validated TNF-alpha as the target of miR-181a by a dual
      luciferase assay. In response to adipogenesis, a mimic or inhibitor was used to
      overexpress or reduce miR-181a expression in porcine pre-adipocytes, which were
      then induced into mature adipocytes. Overexpression of miR-181a accelerated
      accumulation of lipid droplets, increased the amount of triglycerides, and
      repressed TNF-alpha protein expression, while the inhibitor had the opposite
      effect. At the same time, TNF-alpha rescued the increased lipogenesis by miR181a
      mimics. Additionally, miR-181a suppression decreased the expression of fatty
      synthesis associated genes PDE3B (phosphodiesterase 3B), LPL (lipoprotein
      lipase), PPARgamma (proliferator-activated receptor-gamma), GLUT1 (glucose
      transporter), GLUT4, adiponectin and FASN (fatty acid synthase), as well as key
      lipolytic genes HSL (hormone-sensitive lipase) and ATGL (adipose triglyceride
      lipase) as revealed by quantitative real-time PCR. Our study provides the first
      evidence of the role of miR-181a in adipocyte differentiation by regulation of
      TNF-alpha, which may became a new therapeutic target for anti-obesity drugs.

PMID- 24098323
TI  - A systematically combined genotype and functional combination analysis of CYP2E1,
      CYP2D6, CYP2C9, CYP2C19 in different geographic areas of mainland China--a basis
      for personalized therapy.
AB  - The cytochrome P450 is the major enzyme involved in drug metabolism. Single CYP
      genotypes and metabolic phenotypes have been widely studied, but no combination
      analysis has been conducted in the context of specific populations and
      geographical areas. This study is the first to systematically analyze the
      combined genotypes and functional combinations of 400 samples of major CYP genes-
      CYP2E1, CYP2D6, CYP2C9, and CYP2C19 in four geographical areas of mainland China.
      167 different genotype combinations were identified, of which 25 had a greater
      than 1% frequency in the Chinese Han population. In addition, phenotypes of the
      four genes for each sample were in line with the predictions of previous studies
      of the four geographical areas. On the basis of the genotype classification, we
      were able to produce a systemic functional combinations analysis for the
      population. 25 of the combinations detected had at least two non-wild phenotypes
      and four showed a frequency above 1%. A bioinformatics analysis of the
      relationship between particular drugs and multi-genes was conducted. This is the
      first systematic study to analyze genotype combinations and functional
      combinations across whole Chinese population and could make a significant
      contribution in the field of personalized medicine and therapy.

PMID- 24098324
TI  - Nutrition Report Cards: an opportunity to improve school lunch selection.
AB  - OBJECTIVE: To explore the feasibility and implementation efficiency of
      Nutritional Report Cards (NRCs) in helping children make healthier food choices
      at school. METHODS: Pilot testing was conducted in a rural New York school
      district (K-12). Over a five-week period, 27 parents received a weekly e-mail
      containing a NRC listing how many meal components (fruits, vegetables, starches,
      milk), snacks, and a-la-carte foods their child selected. We analyzed choices of
      students in the NRC group vs. the control group, both prior to and during the
      intervention period. Point-of-sale system data for a-la-carte items was analyzed
      using Generalized Least Squares regressions with clustered standard errors.
      RESULTS: NRCs encouraged more home conversations about nutrition and more
      awareness of food selections. Despite the small sample, the NRC was associated
      with reduced selection of some items, such as the percentage of those selecting
      cookies which decreased from 14.3 to 6.5 percent. Additionally, despite requiring
      new keys on the check-out registers to generate the NRC, checkout times increased
      by only 0.16 seconds per transaction, and compiling and sending the NRCs required
      a total weekly investment of 30 minutes of staff time. CONCLUSIONS: This test of
      concept suggests that NRCs are a feasible and inexpensive tool to guide children
      towards healthier choices.

PMID- 24098325
TI  - Single-cell analysis of thymocyte differentiation: identification of
      transcription factor interactions and a major stochastic component in alphabeta
      lineage commitment.
AB  - T cell commitment and alphabeta/gammadelta lineage specification in the thymus
      involves interactions between many different genes. Characterization of these
      interactions thus requires a multiparameter analysis of individual thymocytes. We
      developed two efficient single-cell methods: (i) the quantitative evaluation of
      the co-expression levels of nine different genes, with a plating efficiency of 99
      100% and a detection limit of 2 mRNA molecules/cell; and (ii) single-cell
      differentiation cultures, in the presence of OP9 cells transfected with the
      thymus Notch1 ligand DeltaL4. We show that during T cell commitment, Gata3 has a
      fundamental, dose-dependent role in maintaining Notch1 expression, with
      thymocytes becoming T-cell-committed when they co-express Notch1, Gata3 and
      Bc11b. Of the transcription factor expression patterns studied here, only that of
      Bcl11b was suggestive of a role in Pu1 down-regulation. Individual thymocytes
      became alphabeta/gammadelta lineage-committed at very different stages (from the
      TN2a stage onwards). However, 20% of TN3 cells are not alphabeta/gammadelta
      lineage committed and TN4 cells comprise two main subpopulations with different
      degrees of maturity. The existence of a correlation between differentiation
      potential and expression of the pre-TCR showed that 83% of alphabeta-committed
      cells do not express the pre-TCR and revealed a major stochastic component in
      alphabeta-lineage specification. 

PMID- 24098326
TI  - Identifying cancer specific functionally relevant miRNAs from gene expression and
      miRNA-to-gene networks using regularized regression.
AB  - Identifying microRNA signatures for the different types and subtypes of cancer
      can result in improved detection, characterization and understanding of cancer
      and move us towards more personalized treatment strategies. However, using
      microRNA's differential expression (tumour versus normal) to determine these
      signatures may lead to inaccurate predictions and low interpretability because of
      the noisy nature of miRNA expression data. We present a method for the selection
      of biologically active microRNAs using gene expression data and microRNA-to-gene
      interaction network. Our method is based on a linear regression with an elastic
      net regularization. Our simulations show that, with our method, the active miRNAs
      can be detected with high accuracy and our approach is robust to high levels of
      noise and missing information. Furthermore, our results on real datasets for
      glioblastoma and prostate cancer are confirmed by microRNA expression
      measurements. Our method leads to the selection of potentially functionally
      important microRNAs. The associations of some of our identified miRNAs with
      cancer mechanisms are already confirmed in other studies (hypoxia related hsa-mir
      210 and apoptosis-related hsa-mir-296-5p). We have also identified additional
      miRNAs that were not previously studied in the context of cancer but are
      coherently predicted as active by our method and may warrant further
      investigation. The code is available in Matlab and R and can be downloaded on
      http://www.cs.toronto.edu/goldenberg/Anna_Goldenberg/Current_Research.html. 

PMID- 24098327
TI  - Questions left unanswered: how the brain responds to missing information.
AB  - It sometimes happens that when someone asks a question, the addressee does not
      give an adequate answer, for instance by leaving out part of the required
      information. The person who posed the question may wonder why the information was
      omitted, and engage in extensive processing to find out what the partial answer
      actually means. The present study looks at the neural correlates of the pragmatic
      processes invoked by partial answers to questions. Two experiments are presented
      in which participants read mini-dialogues while their Event-Related brain
      Potentials (ERPs) are being measured. In both experiments, violating the
      dependency between questions and answers was found to lead to an increase in the
      amplitude of the P600 component. We interpret these P600-effects as reflecting
      the increased effort in creating a coherent representation of what is
      communicated. This effortful processing might include the computation of what the
      dialogue participant meant to communicate by withholding information. Our study
      is one of few investigating language processing in conversation, be it that our
      participants were 'eavesdroppers' instead of real interactants. Our results
      contribute to the as of yet small range of pragmatic phenomena that modulate the
      processes underlying the P600 component, and suggest that people immediately
      attempt to regain cohesion if a question-answer dependency is violated in an
      ongoing conversation. 

PMID- 24098329
TI  - Mortality and life expectancy in homeless men and women in Rotterdam: 2001-2010.
AB  - BACKGROUND: Data on mortality among homeless people are limited. Therefore, this
      study aimed to describe mortality patterns within a cohort of homeless adults in
      Rotterdam (the Netherlands) and to assess excess mortality as compared to the
      general population in that city. METHODS: Based on 10-year follow-up of homeless
      adults aged >= 20 years who visited services for homeless people in Rotterdam in
      2001, and on vital statistics, we assessed the association of mortality with age,
      sex and type of service used (e.g. only day care, convalescence care, other)
      within the homeless cohort, and also compared mortality between the homeless and
      general population using Poisson regression. Life tables and decomposition
      methods were used to examine differences in life expectancy. RESULTS: During
      follow-up, of the 2096 adult homeless 265 died. Among the homeless, at age 30
      years no significant sex differences were found in overall mortality rates and
      life expectancy. Compared with the general Rotterdam population, mortality rates
      were 3.5 times higher in the homeless cohort. Excess mortality was larger in
      women (rate ratio [RR] RR 5.56, 95% CI 3.95-7.82) as compared to men (RR 3.31,
      95% CI 2.91-3.77), and decreased with age (RR 7.67, 95% CI 6.87-8.56 for the age
      group 20-44 and RR 1.63, 95% CI 1.41-1.88 for the age group 60+ years). Life
      expectancy at age 30 years was 11.0 (95% CI 9.1-12.9) and 15.9 (95% CI 10.3-21.5)
      years lower for homeless men and women compared to men and women in the general
      population respectively. CONCLUSION: Homeless adults face excessive losses in
      life expectancy, with greatest disadvantages among homeless women and the younger
      age groups.

PMID- 24098328
TI  - VEGF-mediated proliferation of human adipose tissue-derived stem cells.
AB  - Human adipose tissue-derived stem cells (ADSCs) are an attractive multipotent
      stem cell source with therapeutic applicability across diverse fields for the
      repair and regeneration of acute and chronically damaged tissues. In recent
      years, there has been increasing interest in ADSC for tissue engineering
      applications. However, the mechanisms underlying the regulation of ADSC
      proliferation are not fully understood. Here we show that 47 transcripts are up
      regulated while 23 are down-regulated in ADSC compared to terminally
      differentiated cells based on global mRNA profiling and microRNA profiling. Among
      the up-regulated genes, the expression of vascular endothelial growth factor
      (VEGF) is fine-tuned by miR-199a-5p. Further investigation indicates that VEGF
      accelerates ADSC proliferation whereas the multipotency of ADSC remains stable in
      terms of adipogenic, chondrogenic and osteogenic potentials after VEGF treatment,
      suggesting that VEGF may serve as an excellent supplement for accelerating ADSC
      proliferation during in vitro expansion. 

PMID- 24098330
TI  - Two wheat glutathione peroxidase genes whose products are located in chloroplasts
      improve salt and H2O2 tolerances in Arabidopsis.
AB  - Oxidative stress caused by accumulation of reactive oxygen species (ROS) is
      capable of damaging effects on numerous cellular components. Glutathione
      peroxidases (GPXs, EC 1.11.1.9) are key enzymes of the antioxidant network in
      plants. In this study, W69 and W106, two putative GPX genes, were obtained by de
      novo transcriptome sequencing of salt-treated wheat (Triticum aestivum)
      seedlings. The purified His-tag fusion proteins of W69 and W106 reduced H2O2 and
      t-butyl hydroperoxide (t-BHP) using glutathione (GSH) or thioredoxin (Trx) as an
      electron donor in vitro, showing their peroxidase activity toward H2O2 and toxic
      organic hydroperoxide. GFP fluorescence assays revealed that W69 and W106 are
      localized in chloroplasts. Quantitative real-time PCR (Q-RT-PCR) analysis showed
      that two GPXs were differentially responsive to salt, drought, H2O2, or ABA.
      Isolation of the W69 and W106 promoters revealed some cis-acting elements
      responding to abiotic stresses. Overexpression of W69 and W106 conferred strong
      tolerance to salt, H2O2, and ABA treatment in Arabidopsis. Moreover, the
      expression levels of key regulator genes (SOS1, RbohD and ABI1/ABI2) involved in
      salt, H2O2 and ABA signaling were altered in the transgenic plants. These
      findings suggest that W69 and W106 not only act as scavengers of H2O2 in
      controlling abiotic stress responses, but also play important roles in salt and
      ABA signaling. 

PMID- 24098331
TI  - A polymorphism at position 400 in the connection subdomain of HIV-1 reverse
      transcriptase affects sensitivity to NNRTIs and RNaseH activity.
AB  - Reverse transcriptase (RT) plays an essential role in HIV-1 replication, and
      inhibition of this enzyme is a key component of HIV-treatment. However, the use
      of RT inhibitors can lead to the emergence of drug-resistant variants. Until
      recently, most clinically relevant resistance mutations were found in the
      polymerase domain of RT. Lately, an increasing number of resistance mutations has
      been identified in the connection and RNaseH domain. To further explore the role
      of these domains we analyzed the complete RT sequence of HIV-1 subtype B patients
      failing therapy. Position A/T400 in the connection subdomain is polymorphic, but
      the proportion of T400 increases from 41% in naive patients to 72% in patients
      failing therapy. Previous studies suggested a role for threonine in conferring
      resistance to nucleoside RT inhibitors. Here we report that T400 also mediates
      resistance to non-nucleoside RT inhibitors. The susceptibility to NVP and EFV was
      reduced 5-fold and 2-fold, respectively, in the wild-type subtype B NL4.3
      background. We show that substitution A400T reduces the RNaseH activity. The
      changes in enzyme activity are remarkable given the distance to both the
      polymerase and RNaseH active sites. Molecular dynamics simulations were
      performed, which provide a novel atomistic mechanism for the reduction in RNaseH
      activity induced by T400. Substitution A400T was found to change the conformation
      of the RNaseH primer grip region. Formation of an additional hydrogen bond
      between residue T400 and E396 may play a role in this structural change. The
      slower degradation of the viral RNA genome may provide more time for dissociation
      of the bound NNRTI from the stalled RT-template/primer complex, after which
      reverse transcription can resume. 

PMID- 24098332
TI  - Major changes in a rhythmic ball-bouncing task occur at age 7 years.
AB  - The aim of the study was to investigate the development of a rhythmical skill of
      children aged from 5 to 12 years old. Five age groups (5-6, 7-8, 9-10, 11-12, and
      young adults) performed a virtual ball bouncing task (16 forty-second long test
      trials). Task performances, racket oscillation, ball-racket impacts as well as
      the ball-racket coupling were analysed. The results showed a change in both
      performance and behaviour at the age of 7 years old. Before this age, children
      exhibited restricted perceptual-motor coordination with a high frequency of
      racket oscillation and a poor level of performance. After the age of 7, cycle-to
      cycle adaptive coordination based on visual information was progressively
      acquired leading to increasing performance levels with age. Overall these results
      revealed a rapid change in capability to perform the ball bouncing task across
      age with a late emergence of the required coordination and significant change in
      the coordination at the age of 7. 

PMID- 24098333
TI  - Antioxidant N-acetylcysteine attenuates hepatocarcinogenesis by inhibiting ROS/ER
      stress in TLR2 deficient mouse.
AB  - Hepatocellular carcinoma (HCC) remains one of the most deadly solid tumor
      malignancies worldwide. We recently find that the loss of toll-like receptor 2
      (TLR2) activities promotes the diethylnitrosamine (DEN) induced hepatocellular
      carcinogenesis and tumor progression, which associates with an abundant
      accumulation of reactive oxygen species (ROS) and endoplasmic reticulum (ER)
      stress. This finding suggests that the ROS/ER stress plays a role in TLR2
      modulated carcinogenesis of HCC. To investigate the mechanism of TLR2 activity
      defending against hepatocarcinogenesis, the TLR2-deficient mice were treated with
      or without antioxidant N-acetylcysteine (NAC) before DEN administration. We found
      that pretreatment of these animals with NAC attenuated carcinogenesis and
      progression of HCC in the TLR2-deficient mice, declined ROS/ER stress, and
      alleviated the unfold protein response and inflammatory response in TLR2
      deficient liver tissue. Moreover, the NAC treatment significantly reduced the
      enhanced aggregation of p62 and Mallory-Denk bodies in the DEN-induced HCC liver
      tissue, suggesting that NAC treatment improves the suppressive autophagic flux in
      the TLR2-deficient liver. These findings indicate that TLR2 activity defends
      against hepatocarcinogenesis through diminishing the accumulation of ROS and
      alleviating ER stress and unfold protein response mediated inflammatory response
      in the liver. 

PMID- 24098334
TI  - Sporadic colorectal cancer development shows rejuvenescence regarding epithelial
      proliferation and apoptosis.
AB  - BACKGROUND AND AIMS: Sporadic colorectal cancer (CRC) development is a sequential
      process showing age-dependency, uncontrolled epithelial proliferation and
      decreased apoptosis. During juvenile growth cellular proliferation and apoptosis
      are well balanced, which may be perturbed upon aging. Our aim was to correlate
      proliferative and apoptotic activities in aging human colonic epithelium and
      colorectal cancer. We also tested the underlying molecular biology concerning the
      proliferation- and apoptosis-regulating gene expression alterations. MATERIALS
      AND METHODS: Colorectal biopsies from healthy children (n1 = 14), healthy adults
      (n2 = 10), adult adenomas (n3 = 10) and CRCs (n4 = 10) in adults were tested for
      Ki-67 immunohistochemistry and TUNEL apoptosis assay. Mitosis- and apoptosis
      related gene expression was also studied in healthy children (n1 = 6), adult (n2
      = 41) samples and in CRC (n3 = 34) in HGU133plus2.0 microarray platform. Measured
      alterations were confirmed with RT-PCR both on dependent and independent sample
      sets (n1 = 6, n2 = 6, n3 = 6). RESULTS: Mitotic index (MI) was significantly
      higher (p<0.05) in intact juvenile (MI = 0.33+/-0.06) and CRC samples (MI =
      0.42+/-0.10) compared to healthy adult samples (MI = 0.15+/-0.06). In contrast,
      apoptotic index (AI) was decreased in children (0.13+/-0.06) and significantly
      lower in cancer (0.06+/-0.03) compared to healthy adult samples (0.17+/-0.05).
      Eight proliferation- (e.g. MKI67, CCNE1) and 11 apoptosis-associated genes (e.g.
      TNFSF10, IFI6) had altered mRNA expression both in the course of normal aging and
      carcinogenesis, mainly inducing proliferation and reducing apoptosis compared to
      healthy adults. Eight proliferation-associated genes including CCND1, CDK1, CDK6
      and 26 apoptosis-regulating genes (e.g. SOCS3) were differently expressed between
      juvenile and cancer groups mostly supporting the pronounced cell growth in CRC.
      CONCLUSION: Colorectal samples from children and CRC patients can be
      characterized by similarly increased proliferative and decreased apoptotic
      activities compared to healthy colonic samples from adults. Therefore, cell
      kinetic alterations during colorectal cancer development show uncontrolled
      rejuvenescence as opposed to the controlled cell growth in juvenile colonic
      epithelium.

PMID- 24098335
TI  - High-throughput RNA sequencing of pseudomonas-infected Arabidopsis reveals hidden
      transcriptome complexity and novel splice variants.
AB  - We report the results of a genome-wide analysis of transcription in Arabidopsis
      thaliana after treatment with Pseudomonas syringae pathovar tomato. Our time
      course RNA-Seq experiment uses over 500 million read pairs to provide a detailed
      characterization of the response to infection in both susceptible and resistant
      hosts. The set of observed differentially expressed genes is consistent with
      previous studies, confirming and extending existing findings about genes likely
      to play an important role in the defense response to Pseudomonas syringae. The
      high coverage of the Arabidopsis transcriptome resulted in the discovery of a
      surprisingly large number of alternative splicing (AS) events--more than 44% of
      multi-exon genes showed evidence for novel AS in at least one of the probed
      conditions. This demonstrates that the Arabidopsis transcriptome annotation is
      still highly incomplete, and that AS events are more abundant than expected. To
      further refine our predictions, we identified genes with statistically
      significant changes in the ratios of alternative isoforms between treatments.
      This set includes several genes previously known to be alternatively spliced or
      expressed during the defense response, and it may serve as a pool of candidate
      genes for regulated alternative splicing with possible biological relevance for
      the defense response against invasive pathogens.

PMID- 24098336
TI  - Bee products prevent agrichemical-induced oxidative damage in fish.
AB  - In southern South America and other parts of the world, aquaculture is an
      activity that complements agriculture. Small amounts of agrichemicals can reach
      aquaculture ponds, which results in numerous problems caused by oxidative stress
      in non-target organisms. Substances that can prevent or reverse agrichemical
      induced oxidative damage may be used to combat these effects. This study includes
      four experiments. In each experiment, 96 mixed-sex, 6-month-old Rhamdia quelen
      (118+/-15 g) were distributed into eight experimental groups: a control group
      that was not exposed to contaminated water, three groups that were exposed to
      various concentrations of bee products, three groups that were exposed to various
      concentrations of bee products plus tebuconazole (TEB; Folicur 200 CETM) and a
      group that was exposed to 0.88 mg L(-1) of TEB alone (corresponding to 16.6% of
      the 96-h LC50). We show that waterborne bee products, including royal jelly (RJ),
      honey (H), bee pollen (BP) and propolis (P), reversed the oxidative damage caused
      by exposure to TEB. These effects were likely caused by the high polyphenol
      contents of these bee-derived compounds. The most likely mechanism of action for
      the protective effects of bee products against tissue oxidation and the resultant
      damage is that the enzymatic activities of superoxide dismutase (SOD), catalase
      (CAT) and glutathione-S-transferase (GST) are increased. 

PMID- 24098337
TI  - Extrapulmonary tuberculosis: Mycobacterium tuberculosis strains and host risk
      factors in a large urban setting in Brazil.
AB  - BACKGROUND: Factors related to the development of extrapulmonary forms of
      tuberculosis (EPTB) are still poorly understood, particularly in high-endemic
      countries like Brazil. The objective of the paper is to determine host and
      Mycobacterium tuberculosis (MTB) strain-related factors associated with the
      development of EPTB in Espirito Santo state, Brazil. METHODS AND FINDINGS: We
      conducted a retrospective laboratory-based surveillance study of new tuberculosis
      (TB) cases diagnosed in Espirito Santo state, Brazil between 1998 and 2007. We
      genotyped 612 isolates of MTB from 606 TB patients using spoligotyping and IS6110
      restriction fragment length polymorphism (RFLP) typing and compared
      sociodemographic and clinical characteristics of patients with pulmonary TB (PTB)
      and EPTB. Among 606 patients, 464 (77%) had PTB, 79 (13%) had EPTB, 51 (8%) had
      both, and 12 (2%) had miliary TB. The IS6110 RFLP analysis demonstrated that 250
      (41%) isolates belonged to clustered RFLP patterns, 27 (11%) of which were from
      EPTB. We identified 73 clusters including 35 (48%) composed of 2 isolates each.
      By spoligotyping, 506 (83%) MTB isolates fell into known patterns and 106 (17%)
      fell into patterns with no family assignment; 297 (48%) isolates belonged to the
      Latin-American Mediterranean family. Higher school level (4-7 years OR: 0.16 95%
      CI 0.34-0.73 and > 8 years of education, OR 0.06 95% CI 0.009-0.50) white
      ethnicity (OR: 2.54 95% CI 1.03-6.25) and HIV infection (OR: 16.83 95% CI 5.23
      54.18) were associated with EPTB. No specific strain lineage or percentage of
      clustering was associated with EPTB. CONCLUSIONS: These results demonstrate that
      risk factors for EPTB are related more to host than to MTB strain lineage
      characteristics.

PMID- 24098338
TI  - Highlighting entanglement of cultures via ranking of multilingual Wikipedia
      articles.
AB  - How different cultures evaluate a person? Is an important person in one culture
      is also important in the other culture? We address these questions via ranking of
      multilingual Wikipedia articles. With three ranking algorithms based on network
      structure of Wikipedia, we assign ranking to all articles in 9 multilingual
      editions of Wikipedia and investigate general ranking structure of PageRank,
      CheiRank and 2DRank. In particular, we focus on articles related to persons,
      identify top 30 persons for each rank among different editions and analyze
      distinctions of their distributions over activity fields such as politics, art,
      science, religion, sport for each edition. We find that local heroes are dominant
      but also global heroes exist and create an effective network representing
      entanglement of cultures. The Google matrix analysis of network of cultures shows
      signs of the Zipf law distribution. This approach allows to examine diversity and
      shared characteristics of knowledge organization between cultures. The developed
      computational, data driven approach highlights cultural interconnections in a new
      perspective. Dated: June 26, 2013.

PMID- 24098339
TI  - Analysis of nonlinear gene expression progression reveals extensive pathway and
      age-specific transitions in aging human brains.
AB  - Several recent gene expression studies identified hundreds of genes that are
      correlated with age in brain and other tissues in human. However, these studies
      used linear models of age correlation, which are not well equipped to model
      abrupt changes associated with particular ages. We developed a computational
      algorithm for age estimation in which the expression of each gene is treated as a
      dichotomized biomarker for whether the subject is older or younger than a
      particular age. In addition, for each age-informative gene our algorithm
      identifies the age threshold with the most drastic change in expression level,
      which allows us to associate genes with particular age periods. Analysis of human
      aging brain expression datasets from three frontal cortex regions showed that
      different pathways undergo transitions at different ages, and the distribution of
      pathways and age thresholds varies across brain regions. Our study reveals age
      correlated expression changes at particular age points and allows one to estimate
      the age of an individual with better accuracy than previously published methods. 

PMID- 24098340
TI  - Characterization of the mechanism of inhibin alpha-subunit gene in mouse anterior
      pituitary cells by RNA interference.
AB  - Inhibin, a member of the transforming growth factor-beta [TGF-beta] superfamily,
      is a suppressor of follicle-stimulating hormone [FSH] release through pituitary
      gonadal negative feedback loop to regulate follicular development. In this study,
      Inhibin alpha-subunit [Inha] gene was knocked down successfully in mice primary
      anterior pituitary cells at both transcriptional and translational levels by RNAi
      Ready pSIREN-RetroQ-ZsGreen Vector mediated recombinant pshRNA vectors. The
      results indicated that inhibin silencing significantly promoted apoptosis by up
      regulating Caspase-3, Bax and Bcl-2 genes without affecting p53 both at
      transcriptional and translational levels. Furthermore, it markedly impaired the
      progression of G1 phase of cell cycle and decreased the amount of cells in S
      phase [as detected by flow cytometry]. Inhibin silencing resulted in significant
      up-regulation of mRNA and protein expressions of Gondotropin releasing hormone
      receptors [GnRHR] and down-regulated mRNA levels of beta-glycans with parellel
      change in the amount of its protein expression. Silencing of inhibin-a
      significantly increased [P<0.05] activin-beta concentration without affecting FSH
      and LH levels in anterior pituitary cells. These findings revealed that up
      regulation of GnRH receptors by silencing inhibin a-subunit gene might increase
      the concentration of activin-beta in the culture medium. Inhibin a silencing
      resulted in increased mRNA and protein expressions of inhibinbeta which may
      demonstrate that both inhibin subunits co-participate in the regulation of
      reproductive events in anterior pituitary cells. This study concludes that
      inhibin is a broad regulatory marker in anterior pituitary cells by regulating
      apoptosis, cellular progression and simultaneously by vital fluctuations in the
      hormonal signaling. 

PMID- 24098341
TI  - Increased oxidative metabolism and neurotransmitter cycling in the brain of mice
      lacking the thyroid hormone transporter SLC16A2 (MCT8).
AB  - Mutations of the monocarboxylate transporter 8 (MCT8) cause a severe X-linked
      intellectual deficit and neurological impairment. MCT8 is a specific thyroid
      hormone (T4 and T3) transporter and the patients also present unusual
      abnormalities in the serum profile of thyroid hormone concentrations due to
      altered secretion and metabolism of T4 and T3. Given the role of thyroid hormones
      in brain development, it is thought that the neurological impairment is due to
      restricted transport of thyroid hormones to the target neurons. In this work we
      have investigated cerebral metabolism in mice with Mct8 deficiency. Adult male
      mice were infused for 30 minutes with (1-(13)C) glucose and brain extracts
      prepared and analyzed by (13)C nuclear magnetic resonance spectroscopy. Genetic
      inactivation of Mct8 resulted in increased oxidative metabolism as reflected by
      increased glutamate C4 enrichment, and of glutamatergic and GABAergic
      neurotransmissions as observed by the increases in glutamine C4 and GABA C2
      enrichments, respectively. These changes were distinct to those produced by
      hypothyroidism or hyperthyroidism. Similar increments in glutamate C4 enrichment
      and GABAergic neurotransmission were observed in the combined inactivation of
      Mct8 and D2, indicating that the increased neurotransmission and metabolic
      activity were not due to increased production of cerebral T3 by the D2-encoded
      type 2 deiodinase. In conclusion, Mct8 deficiency has important metabolic
      consequences in the brain that could not be correlated with deficiency or excess
      of thyroid hormone supply to the brain during adulthood. 

PMID- 24098342
TI  - Frequency and pattern of heteroplasmy in the complete human mitochondrial genome.
AB  - Determining the levels of human mitochondrial heteroplasmy is of utmost
      importance in several fields. In spite of this, there are currently few published
      works that have focused on this issue. In order to increase the knowledge of
      mitochondrial DNA (mtDNA) heteroplasmy, the main goal of this work is to
      investigate the frequency and the mutational spectrum of heteroplasmy in the
      human mtDNA genome. To address this, a set of nine primer pairs designed to avoid
      co-amplification of nuclear DNA (nDNA) sequences of mitochondrial origin (NUMTs)
      was used to amplify the mitochondrial genome in 101 individuals. The analysed
      individuals represent a collection with a balanced representation of genders and
      mtDNA haplogroup distribution, similar to that of a Western European population.
      The results show that the frequency of heteroplasmic individuals exceeds 61%. The
      frequency of point heteroplasmy is 28.7%, with a widespread distribution across
      the entire mtDNA. In addition, an excess of transitions in heteroplasmy were
      detected, suggesting that genetic drift and/or selection may be acting to reduce
      its frequency at population level. In fact, heteroplasmy at highly stable
      positions might have a greater impact on the viability of mitochondria,
      suggesting that purifying selection must be operating to prevent their fixation
      within individuals. This study analyses the frequency of heteroplasmy in a
      healthy population, carrying out an evolutionary analysis of the detected changes
      and providing a new perspective with important consequences in medical,
      evolutionary and forensic fields. 

PMID- 24098343
TI  - Genome-wide association study of gene by smoking interactions in coronary artery
      calcification.
AB  - Many GWAS have identified novel loci associated with common diseases, but have
      focused only on main effects of individual genetic variants rather than
      interactions with environmental factors (GxE). Identification of GxE interactions
      is particularly important for coronary heart disease (CHD), a major preventable
      source of morbidity and mortality with strong non-genetic risk factors.
      Atherosclerosis is the major cause of CHD, and coronary artery calcification
      (CAC) is directly correlated with quantity of coronary atherosclerotic plaque. In
      the current study, we tested for genetic variants influencing extent of CAC via
      interaction with smoking (GxS), by conducting a GxS discovery GWAS in Genetic
      Epidemiology Network of Arteriopathy (GENOA) sibships (N = 915 European
      Americans) followed by replication in Framingham Heart Study (FHS) sibships (N =
      1025 European Americans). Generalized estimating equations accounted for the
      correlation within sibships in strata-specific groups of smokers and nonsmokers,
      as well as GxS interaction. Primary analysis found SNPs that showed suggestive
      associations (p<=10(-5)) in GENOA GWAS, but these index SNPs did not replicate in
      FHS. However, secondary analysis was able to replicate candidate gene regions in
      FHS using other SNPs (+/-250 kb of GENOA index SNP). In smoker and nonsmoker
      groups, replicated genes included TCF7L2 (p = 6.0*10(-5)) and WWOX (p = 4.5*10(
      6)); and TNFRSF8 (p = 7.8*10(-5)), respectively. For GxS interactions, replicated
      genes included TBC1D4 (p = 6.9*10(-5)) and ADAMTS9 (P = 7.1*10(-5)).
      Interestingly, these genes are involved in inflammatory pathways mediated by the
      NF-kappaB axis. Since smoking is known to induce chronic and systemic
      inflammation, association of these genes likely reflects roles in CAC development
      via inflammatory pathways. Furthermore, the NF-kappaB axis regulates bone
      remodeling, a key physiological process in CAC development. In conclusion, GxS
      GWAS has yielded evidence for novel loci that are associated with CAC via
      interaction with smoking, providing promising new targets for future population
      based and functional studies of CAC development. 

PMID- 24098344
TI  - Creatine kinase-overexpression improves myocardial energetics, contractile
      dysfunction and survival in murine doxorubicin cardiotoxicity.
AB  - Doxorubicin (DOX) is a commonly used life-saving antineoplastic agent that also
      causes dose-dependent cardiotoxicity. Because ATP is absolutely required to
      sustain normal cardiac contractile function and because impaired ATP synthesis
      through creatine kinase (CK), the primary myocardial energy reserve reaction, may
      contribute to contractile dysfunction in heart failure, we hypothesized that
      impaired CK energy metabolism contributes to DOX-induced cardiotoxicity. We
      therefore overexpressed the myofibrillar isoform of CK (CK-M) in the heart and
      determined the energetic, contractile and survival effects of CK-M following
      weekly DOX (5 mg/kg) administration using in vivo (31)P MRS and (1)H MRI. In
      control animals, in vivo cardiac energetics were reduced at 7 weeks of DOX
      protocol and this was followed by a mild but significant reduction in left
      ventricular ejection fraction (EF) at 8 weeks of DOX, as compared to baseline. At
      baseline, CK-M overexpression (CK-M-OE) increased rates of ATP synthesis through
      cardiac CK (CK flux) but did not affect contractile function. Following DOX
      however, CK-M-OE hearts had better preservation of creatine phosphate and higher
      CK flux and higher EF as compared to control DOX hearts. Survival after DOX
      administration was significantly better in CK-M-OE than in control animals
      (p<0.02). Thus CK-M-OE attenuates the early decline in myocardial high-energy
      phosphates and contractile function caused by chronic DOX administration and
      increases survival. These findings suggest that CK impairment plays an energetic
      and functional role in this DOX-cardiotoxicity model and suggests that metabolic
      strategies, particularly those targeting CK, offer an appealing new strategy for
      limiting DOX-associated cardiotoxicity.

PMID- 24098345
TI  - The Sinorhizobium fredii HH103 lipopolysaccharide is not only relevant at early
      soybean nodulation stages but also for symbiosome stability in mature nodules.
AB  - In this work we have characterised the Sinorhizobium fredii HH103 greA lpsB
      lpsCDE genetic region and analysed for the first time the symbiotic performance
      of Sinorhizobium fredii lps mutants on soybean. The organization of the S. fredii
      HH103 greA, lpsB, and lpsCDE genes was equal to that of Sinorhizobium meliloti
      1021. S. fredii HH103 greA, lpsB, and lpsE mutant derivatives produced altered
      LPS profiles that were characteristic of the gene mutated. In addition, S. fredii
      HH103 greA mutants showed a reduction in bacterial mobility and an increase of
      auto-agglutination in liquid cultures. RT-PCR and qPCR experiments demonstrated
      that the HH103 greA gene has a positive effect on the transcription of lpsB.
      Soybean plants inoculated with HH103 greA, lpsB or lpsE mutants formed numerous
      ineffective pseudonodules and showed severe symptoms of nitrogen starvation.
      However, HH103 greA and lps mutants were also able to induce the formation of a
      reduced number of soybean nodules of normal external morphology, allowing the
      possibility of studying the importance of bacterial LPS in later stages of the S.
      fredii HH103-soybean symbiosis. The infected cells of these nodules showed signs
      of early termination of symbiosis and lytical clearance of bacteroids. These
      cells also had very thick walls and accumulation of phenolic-like compounds,
      pointing to induced defense reactions. Our results show the importance of
      bacterial LPS in later stages of the S. fredii HH103-soybean symbiosis and their
      role in preventing host cell defense reactions. S. fredii HH103 lpsB mutants also
      showed reduced nodulation with Vigna unguiculata, although the symbiotic
      impairment was less pronounced than in soybean. 

PMID- 24098346
TI  - Using oxidized low-density lipoprotein autoantibodies to predict restenosis after
      balloon angioplasty in patients with acute myocardial infarction.
AB  - OBJECTIVES: Oxidized low-density lipoproteins (oxLDL) and oxidized low-density
      lipoprotein autoantibodies (OLAB) have been detected in human plasma and
      atherosclerotic lesions. OLAB appear to play a role in the clearance of oxLDL
      from circulation. Higher levels of OLAB appear to be associated with a reduced
      risk of a wide range of cardiovascular diseases. We investigated the prognostic
      value of plasma oxLDL and OLAB in patients undergoing primary coronary balloon
      angioplasty for acute ST-elevation myocardial infarction (STEMI). METHODS: Plasma
      oxLDL and OLAB concentrations were measured in 56 patients with acute STEMI
      before primary angioplasty, and then 3 days, 7 days and 1 month after the acute
      event. Follow-up angiography was repeated 6 months later to detect the presence
      of restensosis (defined as >50% luminal diameter stenosis). The thrombolysis in
      myocardial infarction (TIMI) risk score was calculated to determine the
      relationship between OLAB/oxLDL ratio and TIMI risk scores. RESULTS: Of the 56
      patients, 18 (31%) had angiographic evidence of restenosis. Plasma OLAB
      concentrations were significantly lower in the restenosis group before
      angioplasty (181+/-114 vs. 335+/-257 U/L, p = 0.003), and at day 3 (155+/-92 vs.
      277+/-185 U/L, p<0.001) and day 7 (177+/-110 vs. 352+/-279 U/L, p<0.001) after
      the acute event. There was no difference in oxLDL concentration between the two
      groups. The ratio of OLAB/oxLDL positively correlated with TIMI risk scores
      before angioplasty (p for trend analysis, p = 0.004), at day 3 (p = 0.008) and
      day 7 (p<0.001) after STEMI. SIGNIFICANCE: A relative deficit of OLAB, and hence
      likely impaired clearance of oxLDL, is associated with the risk of arterial
      restenosis after primary angioplasty for acute STEMI.

PMID- 24098347
TI  - Association between inflammatory infiltrates and isolated monosomy 22/del(22q) in
      meningiomas.
AB  - Meningiomas contain highly variable levels of infiltrating tissue macrophages
      (TiMa) and other immune cells. In this study we investigated the potential
      association between the number and immunophenotype of inflammatory and other
      immune cells infiltrating the tumor as evaluated by multiparameter flow
      cytometry, and the clinico-biological, cytogenetic and gene expression profile
      (GEP) of 75 meningioma patients. Overall, our results showed a close association
      between the amount and cellular composition of the inflammatory and other immune
      cell infiltrates and the cytogenetic profile of the tumors. Notably, tumors with
      isolated monosomy 22/del(22q) showed greater numbers of TiMa, NK cells and
      (recently)-activated CD69(+) lymphocytes versus meningiomas with diploid and
      complex karyotypes. In addition, in the former cytogenetic subgroup of
      meningiomas, tumor-infiltrating TiMa also showed a more activated and
      functionally mature phenotype, as reflected by a greater fraction of CD69(+),
      CD63(+), CD16(+) and CD33(+) cells. GEP at the mRNA level showed a unique GEP
      among meningiomas with an isolated monosomy 22/del(22q) versus all other cases,
      which consisted of increased expression of genes involved in inflammatory/immune
      response, associated with an M1 TiMa phenotype. Altogether, these results suggest
      that loss of expression of specific genes coded in chromosome 22 (e.g. MIF) is
      closely associated with an increased homing and potentially also anti-tumoral
      effect of TiMa, which could contribute to explain the better outcome of this
      specific good-prognosis cytogenetic subgroup of meningiomas. 

PMID- 24098349
TI  - Determination and modulation of total and surface calcium-sensing receptor
      expression in monocytes in vivo and in vitro.
AB  - Expression of the calcium-sensing receptor (CaSR) has previously been
      demonstrated in human circulating monocytes (HCM). The present study was designed
      to measure CaSR expression in HCM and to examine its potential modulation by pro
      inflammatory cytokines, Ca2+, vitamin D sterols in U937 cell line. Twenty healthy
      volunteers underwent blood sampling with subsequent isolation of peripheral blood
      mononuclear cells (PBMC) at 3 visits. Flow cytometry analysis (FACS) was
      performed initially (V1) and 19 days later (V2) to examine intra- and
      intersubject fluctuations of total and surface CaSR expression in HCM and 15
      weeks later (V3) to study the effect of vitamin D supplementation. In vitro
      experiments were conducted to assess the effects of pro-inflammatory cytokines,
      calcidiol, calcitriol and Ca2+ on CaSR expression in U937 cell line. By FACS
      analysis, more than 95% of HCM exhibited cell surface CaSR staining. In contrast,
      CaSR staining failed to detect surface CaSR expression in other PBMC. After cell
      permeabilization, total CaSR expression was observed in more than 95% of all
      types of PBMC. Both total and surface CaSR expression in HCM showed a high degree
      of intra-assay reproducibility (<3%) and a moderate intersubject fluctuation. In
      response to vitamin D supplementation, there was no significant change for both
      total and surface CaSR expression. In the in vitro study, U937 cells showed
      strong total and surface CaSR expression, and both were moderately increased in
      response to calcitriol exposure. Neither total nor surface CaSR expression was
      modified by increasing Ca2+ concentrations. Total CaSR expression was
      concentration dependently decreased by TNFalpha exposure. In conclusion, CaSR
      expression can be easily measured by flow cytometry in human circulating
      monocytes. In the in vitro study, total and surface CaSR expression in the U937
      cell line were increased by calcitriol but total CaSR expression was decreased by
      TNFalpha stimulation. 

PMID- 24098348
TI  - Alternative splicing targeting the hTAF4-TAFH domain of TAF4 represses
      proliferation and accelerates chondrogenic differentiation of human mesenchymal
      stem cells.
AB  - Transcription factor IID (TFIID) activity can be regulated by cellular signals to
      specifically alter transcription of particular subsets of genes. Alternative
      splicing of TFIID subunits is often the result of external stimulation of
      upstream signaling pathways. We studied tissue distribution and cellular
      expression of different splice variants of TFIID subunit TAF4 mRNA and
      biochemical properties of its isoforms in human mesenchymal stem cells (hMSCs) to
      reveal the role of different isoforms of TAF4 in the regulation of proliferation
      and differentiation. Expression of TAF4 transcripts with exons VI or VII deleted,
      which results in a structurally modified hTAF4-TAFH domain, increases during
      early differentiation of hMSCs into osteoblasts, adipocytes and chondrocytes.
      Functional analysis data reveals that TAF4 isoforms with the deleted hTAF4-TAFH
      domain repress proliferation of hMSCs and preferentially promote chondrogenic
      differentiation at the expense of other developmental pathways. This study also
      provides initial data showing possible cross-talks between TAF4 and TP53 activity
      and switching between canonical and non-canonical WNT signaling in the processes
      of proliferation and differentiation of hMSCs. We propose that TAF4 isoforms
      generated by the alternative splicing participate in the conversion of the
      cellular transcriptional programs from the maintenance of stem cell state to
      differentiation, particularly differentiation along the chondrogenic pathway. 

PMID- 24098350
TI  - Isolation and characterization of carbendazim-degrading Rhodococcus erythropolis
      djl-11.
AB  - Carbendazim (methyl 1H-benzimidazol-2-yl carbamate) is one of the most widely
      used fungicides in agriculture worldwide, but has been reported to have adverse
      effects on animal health and ecosystem function. A highly efficient carbendazim
      degrading bacterium (strain dj1-11) was isolated from carbendazim-contaminated
      soil samples via enrichment culture. Strain dj1-11 was identified as Rhodococcus
      erythropolis based on morphological, physiological and biochemical characters,
      including sequence analysis of the 16S rRNA gene. In vitro degradation of
      carbendazim (1000 mg.L(-1)) by dj1-11 in minimal salts medium (MSM) was highly
      efficient, and with an average degradation rate of 333.33 mg.L(-1).d(-1) at 28
      degrees C. The optimal temperature range for carbendazim degradation by dj1-11 in
      MSM was 25-30 degrees C. Whilst strain dj1-11 was capable of metabolizing
      cabendazim as the sole source of carbon and nitrogen, degradation was
      significantly (P<0.05) increased by addition of 12.5 mM NH4NO3. Changes in MSM pH
      (4-9), substitution of NH4NO3 with organic substrates as N and C sources or
      replacing Mg(2+) with Mn(2+), Zn(2+) or Fe(2+) did not significantly affect
      carbendazim degradation by dj1-11. During the degradation process, liquid
      chromatography-mass spectrometry (LC-MS) detected the metabolites 2
      aminobenzimidazole and 2-hydroxybenzimidazole. A putative carbendazim-hydrolyzing
      esterase gene was cloned from chromosomal DNA of djl-11 and showed 99% sequence
      homology to the mheI carbendazim-hydrolyzing esterase gene from Nocardioides sp.
      SG-4G. 

PMID- 24098351
TI  - Genome-wide association study for cytokines and immunoglobulin G in swine.
AB  - Increased disease resistance through improved immune capacity would be beneficial
      for the welfare and productivity of farm animals. To identify genomic regions
      responsible for immune capacity traits in swine, a genome-wide association study
      was conducted. In total, 675 pigs were included. At 21 days of age, all piglets
      were vaccinated with modified live classical swine fever vaccine. Blood samples
      were sampled when the piglets were 20 and 35 days of age, respectively. Four
      traits, including Interferon-gamma (IFN-gamma) and Interleukin 10 (IL-10) levels,
      the ratio of IFN-gamma to IL-10 and Immunoglobulin G (IgG) blocking percentage to
      CSFV in serum were measured. All the samples were genotyped for 62,163 single
      nucleotide polymorphisms (SNP) using the Illumina porcineSNP60k BeadChip. After
      quality control, 46,079 SNPs were selected for association tests based on a
      single-locus regression model. To tackle the issue of multiple testing, 10,000
      permutations were performed to determine the chromosome-wise and genome-wise
      significance level. In total, 32 SNPs with chromosome-wise significance level
      (including 4 SNPs with genome-wise significance level) were identified. These
      SNPs account for 3.23% to 13.81% of the total phenotypic variance individually.
      For the four traits, the numbers of significant SNPs range from 5 to 15, which
      jointly account for 37.52%, 82.94%, 26.74% and 24.16% of the total phenotypic
      variance of IFN-gamma, IL-10, IFN-gamma/IL-10, and IgG, respectively. Several
      significant SNPs are located within the QTL regions reported in previous studies.
      Furthermore, several significant SNPs fall into the regions which harbour a
      number of known immunity-related genes. Results herein lay a preliminary
      foundation for further identifying the causal mutations affecting swine immune
      capacity in follow-up studies. 

PMID- 24098352
TI  - Chemotactic sensing towards ambient and secreted attractant drives collective
      behaviour of E. coli.
AB  - We simulate the dynamics of a suspension of bacterial swimmers, which
      chemotactically sense gradients in either ambient or self-secreted attractants
      (e.g. nutrient or aspartate respectively), or in both. Unlike previous mean field
      models based on a set of continuum partial differential equations, our model
      resolves single swimmers and therefore incorporates stochasticity and effects due
      to fluctuations in the bacterial density field. The algorithm we use is simple
      enough that we can follow the evolution of colonies of up to over a million
      bacteria for timescales relevant to pattern formation for E. coli growing in
      semisolid medium such as agar, or in confined geometries. Our results confirm
      previous mean field results that the patterns observed experimentally can be
      reproduced with a model incorporating chemoattractant secretion, chemotaxis
      (towards gradients in the chemoattractant field), and bacterial reproduction.
      They also suggest that further experiments with bacterial strains chemotactically
      moving up both nutrient and secreted attractant field may yield yet more
      dynamical patterns. 

PMID- 24098353
TI  - Genome-wide copy number variations inferred from SNP genotyping arrays using a
      Large White and Minzhu intercross population.
AB  - Copy number variations (CNVs) are one of the main contributors to genetic
      diversity in animals and are broadly distributed in the genomes of swine.
      Investigating the performance and evolutionary impacts of pig CNVs requires
      comprehensive knowledge of their structure and function within and between
      breeds. In the current study, 4 different programs (i.e., GADA, PennCNV,
      QuantiSNP, and cnvPartition) were used to analyze Porcine SNP60 genotyping data
      of 585 pigs from one Large White * Minzhu intercross population to detect copy
      number variant regions (CNVRs). Overlapping CNVRs recalled by at least 2 programs
      were used to construct a powerful and comprehensive CNVR map, which contained 249
      CNVRs (i.e., 70 gains, 43 losses, and 136 gains/losses) and covered 26.22% of the
      regions in the swine genome. Ten CNVRs, representing different predicted
      statuses, were selected for validation via quantitative real-time PCR (QPCR);
      9/10 CNVRs (i.e., 90%) were validated. When being traced back to the F0
      generation, 58 events were identified in only Minzhu F0 parents and 2 events were
      identified in only Large White F0 parents. A series of CNVR function analyses
      were performed. Some of the CNVRs functions were predicted, and several
      interesting CNVRs for meat quality traits and hematological parameters were
      obtained. A comprehensive and lower false rate genome-wide CNV map was
      constructed for Large White and Minzhu pig genomes in this study. Our results may
      provide an important basis for determining the relationship between CNVRs and
      important qualitative and quantitative traits. In addition, it can help to
      further understand genetic processes in pigs.

PMID- 24098354
TI  - Evaluation of estrogenic potential of flavonoids using a recombinant yeast strain
      and MCF7/BUS cell proliferation assay.
AB  - Phytoestrogens are of interest because of their reported beneficial effects on
      many human maladies including cancer, neurodegeneration, cardiovascular disease
      and diabetes. Furthermore, there is a search for compounds with estrogenic
      activity that can replace estrogen in hormone replacement therapy during
      menopause, without the undesirable effects of estrogen, such as the elevation of
      breast cancer occurrence. Thus, the principal objective of this study was to
      assess the estrogenic activity of flavonoids with different hydroxylation
      patterns: quercetin, kaempferol, luteolin, fisetin, chrysin, galangin, flavone, 3
      hydroxyflavone, 5-hydroxyflavone and 7-hydroxyflavone via two different in vitro
      assays, the recombinant yeast assay (RYA) and the MCF-7 proliferation assay (E
      screen), since the most potent phytoestrogens are members of the flavonoid
      family. In these assays, kaempferol was the only compound that showed ERalpha
      dependent transcriptional activation activity by RYA, showing 6.74+/-1.7 nM EEQ,
      besides acting as a full agonist for the stimulation of proliferation of MCF
      7/BUS cells. The other compounds did not show detectable levels of interaction
      with ER under the conditions used in the RYA. However, in the E-screen assay,
      compounds such as galangin, luteolin and fisetin also stimulated the
      proliferation of MCF-7/BUS cells, acting as partial agonists. In the evaluation
      of antiestrogenicity, the compounds quercetin, chrysin and 3-hydroxyflavone
      significantly inhibited the cell proliferation induced by 17-beta-estradiol in
      the E-screen assay, indicating that these compounds may act as estrogen receptor
      antagonists. Overall, it became clear in the assay results that the estrogenic
      activity of flavonoids was affected by small structural differences such as the
      number of hydroxyl groups, especially those on the B ring of the flavonoid. 

PMID- 24098355
TI  - Improving pharmacy staff knowledge and practice on childhood diarrhea management
      in Vietnam: are educational interventions effective?
AB  - BACKGROUND: In many developing countries, private pharmacies play an important
      role in providing health information and services to local communities for common
      health issues. The aim of this study was to ascertain medium-term impact of
      educational interventions on knowledge and practice of pharmacy staff regarding
      management of childhood diarrhea in Vietnam. METHODS: This was a pre- and post
      intervention study with 32 and 44 months difference from the time of the baseline
      survey to the conclusion of trainings and the time of the end-line survey,
      respectively. Interventions included in-class training for pharmacy staff,
      printed materials at the pharmacy, and supportive supervision. Knowledge/reported
      practice and actual practice of pharmacy staff were measured before and after
      interventions. RESULTS: After interventions, significant improvements (p<0.01)
      were observed for all indexes related to pharmacy staff's knowledge about
      childhood diarrhea; for instance, 31% and 60% of surveyed staff asked about
      weight of the child and accompanying symptoms of childhood diarrhea,
      respectively, an increase from 11% and 45% at the baseline. Oral rehydration
      solution (ORS) was the most frequently reported product recommended (97% to 99%),
      but probiotics and antidiarrheals were the products most frequently prescribed at
      pharmacies. Public health facilities remained the preferred choice for referrals
      from pharmacies, but the use of private clinics was increasing. Consultations and
      advice provided to caregivers also improved, but considerable gaps between
      knowledge and actual practice of staff in real pharmacy settings remained.
      CONCLUSIONS: Educational interventions were effective in improving pharmacy staff
      knowledge and practice regarding management of childhood diarrhea. Knowledge and
      actual practice of staff in real pharmacy settings did not always correlate;
      there is need for a stronger regulatory and law enforcement system. Interventions
      to improve pharmacy practice in developing countries should be focused,
      comprehensive, and evidence-based.

PMID- 24098356
TI  - The roles of APOBEC3G complexes in the incorporation of APOBEC3G into HIV-1.
AB  - BACKGROUND: The incorporation of human APOBEC3G (hA3G) into HIV is required for
      exerting its antiviral activity, therefore the mechanism underlying hA3G virion
      encapsidation has been investigated extensively. hA3G was shown to form low
      molecular-mass (LMM) and high-molecular-mass (HMM) complexes. The function of
      different forms of hA3G in its viral incorporation remains unclear.
      METHODOLOGY/PRINCIPAL FINDINGS: In this study, we investigated the subcellular
      distribution and lipid raft association of hA3G using subcellular fractionation,
      membrane floatation assay and pulse-chase radiolabeling experiments respectively,
      and studied the correlation between the ability of hA3G to form the different
      complex and its viral incorporation. Our work herein provides evidence that the
      majority of newly-synthesized hA3G interacts with membrane lipid raft domains to
      form Lipid raft-associated hA3G (RA hA3G), which serve as the precursor of mature
      HMM hA3G complex, while a minority of newly-synthesized hA3G remains in the
      cytoplasm as a soluble LMM form. The distribution of hA3G among the soluble LMM
      form, the RA LMM form and the mature forms of HMM is regulated by a mechanism
      involving the N-terminal part of the linker region and the C-terminus of hA3G.
      Mutagenesis studies reveal a direct correlation between the ability of hA3G to
      form the RA LMM complex and its viral incorporation. CONCLUSIONS/SIGNIFICANCE:
      Together these data suggest that the Lipid raft-associated LMM A3G complex
      functions as the cellular source of viral hA3G.

PMID- 24098357
TI  - Developmental and activity-dependent miRNA expression profiling in primary
      hippocampal neuron cultures.
AB  - MicroRNAs (miRNAs) are evolutionarily conserved non-coding RNAs of ~22
      nucleotides that regulate gene expression at the level of translation and play
      vital roles in hippocampal neuron development, function and plasticity. Here, we
      performed a systematic and in-depth analysis of miRNA expression profiles in
      cultured hippocampal neurons during development and after induction of neuronal
      activity. MiRNA profiling of primary hippocampal cultures was carried out using
      locked nucleic-acid-based miRNA arrays. The expression of 264 different miRNAs
      was tested in young neurons, at various developmental stages (stage 2-4) and in
      mature fully differentiated neurons (stage 5) following the induction of neuronal
      activity using chemical stimulation protocols. We identified 210 miRNAs in mature
      hippocampal neurons; the expression of most neuronal miRNAs is low at early
      stages of development and steadily increases during neuronal differentiation. We
      found a specific subset of 14 miRNAs with reduced expression at stage 3 and
      showed that sustained expression of these miRNAs stimulates axonal outgrowth.
      Expression profiling following induction of neuronal activity demonstrates that
      51 miRNAs, including miR-134, miR-146, miR-181, miR-185, miR-191 and miR-200a
      show altered patterns of expression after NMDA receptor-dependent plasticity, and
      31 miRNAs, including miR-107, miR-134, miR-470 and miR-546 were upregulated by
      homeostatic plasticity protocols. Our results indicate that specific miRNA
      expression profiles correlate with changes in neuronal development and neuronal
      activity. Identification and characterization of miRNA targets may further
      elucidate translational control mechanisms involved in hippocampal development,
      differentiation and activity-depended processes. 

PMID- 24098358
TI  - Mitochondrial Ca2+-handling in fast skeletal muscle fibers from wild type and
      calsequestrin-null mice.
AB  - Mitochondrial calcium handling and its relation with calcium released from
      sarcoplasmic reticulum (SR) in muscle tissue are subject of lively debate. In
      this study we aimed to clarify how the SR determines mitochondrial calcium
      handling using dCASQ-null mice which lack both isoforms of the major Ca(2+)
      binding protein inside SR, calsequestrin. Mitochondrial free Ca(2+)-concentration
      ([Ca(2+)]mito) was determined by means of a genetically targeted ratiometric FRET
      based probe. Electron microscopy revealed a highly significant increase in
      intermyofibrillar mitochondria (+55%) and augmented coupling (+12%) between
      Ca(2+) release units of the SR and mitochondria in dCASQ-null vs. WT fibers.
      Significant differences in the baseline [Ca(2+)]mito were observed between
      quiescent WT and dCASQ-null fibers, but not in the resting cytosolic Ca(2+)
      concentration. The rise in [Ca(2+)]mito during electrical stimulation occurred in
      20-30 ms, while the decline during and after stimulation was governed by 4 rate
      constants of approximately 40, 1.6, 0.2 and 0.03 s(-1). Accordingly, frequency
      dependent increase in [Ca(2+)]mito occurred during sustained contractions. In
      dCASQ-null fibers the increases in [Ca(2+)]mito were less pronounced than in WT
      fibers and even lower when extracellular calcium was removed. The amplitude and
      duration of [Ca(2+)]mito transients were increased by inhibition of mitochondrial
      Na(+)/Ca(2+) exchanger (mNCX). These results provide direct evidence for fast
      Ca(2+) accumulation inside the mitochondria, involvement of the mNCX in
      mitochondrial Ca(2+)-handling and a dependence of mitochondrial Ca(2+)-handling
      on intracellular (SR) and external Ca(2+) stores in fast skeletal muscle fibers.
      dCASQ-null mice represent a model for malignant hyperthermia. The differences in
      structure and in mitochondrial function observed relative to WT may represent
      compensatory mechanisms for the disease-related reduction of calcium storage
      capacity of the SR and/or SR Ca(2+)-leakage. 

PMID- 24098359
TI  - Association between plasma nonesterified fatty acids species and adipose tissue
      fatty acid composition.
AB  - Fatty acid composition of adipose tissue (AT) is an established long-term
      biomarker for fatty acid (FA) intake and status, but AT samples are not easily
      available. Nonesterified FA composition in plasma (pNEFA) may be a good indicator
      of AT FA composition, because pNEFA are mainly generated by AT lipolysis. We
      investigated the correlation of 42 pNEFA and subcutaneous as well as visceral AT
      FA in 27 non-diabetic women with a median BMI of 36 kg/m(2) (Q0.25: 25 kg/m(2);
      Q0.75: 49 kg/m(2)). Close correlations of pNEFA and AT FA were found for odd
      chain FA (15?0 r = 0.838 and 0.862 for subcutaneous and visceral AT,
      respectively) and omega-3 FA (22?6 r = 0.719/0.535), while no significant or low
      correlations were found for other FA including 18?1 (r = 0.384/0.325) and 20?4 (r
      = 0.386/0.266). Close correlations of pNEFA and AT FA were found for essential
      fatty acids, like 18?2 (r = 0.541/0.610) and 20?5 (r = 0.561/0.543). The lower
      correlation for some pNEFA species with AT FA indicates that the variation of
      most pNEFA is significantly affected by other FA sources and flux of FA to
      tissue, in addition to release from AT. A relevant influence of BMI on the level
      of correlation was shown for saturated FA. NEFA analysis in fasted plasma can
      serve as a virtual AT biopsy for some FA, and as a biomarker for intake of dairy
      products and sea fish. 

PMID- 24098360
TI  - Ribbon crystals.
AB  - A repetitive crystal-like pattern is spontaneously formed upon the twisting of
      straight ribbons. The pattern is akin to a tessellation with isosceles triangles,
      and it can easily be demonstrated with ribbons cut from an overhead transparency.
      We give a general description of developable ribbons using a ruled procedure
      where ribbons are uniquely described by two generating functions. This
      construction defines a differentiable frame, the ribbon frame, which does not
      have singular points, whereby we avoid the shortcomings of the Frenet-Serret
      frame. The observed spontaneous pattern is modeled using planar triangles and
      cylindrical arcs, and the ribbon structure is shown to arise from a maximization
      of the end-to-end length of the ribbon, i.e. from an optimal use of ribbon
      length. The phenomenon is discussed in the perspectives of incompatible intrinsic
      geometries and of the emergence of long-range order. 

PMID- 24098362
TI  - Weather forecasting by insects: modified sexual behaviour in response to
      atmospheric pressure changes.
AB  - Prevailing abiotic conditions may positively or negatively impact insects at both
      the individual and population levels. For example while moderate rainfall and
      wind velocity may provide conditions that favour development, as well as movement
      within and between habitats, high winds and heavy rains can significantly
      decrease life expectancy. There is some evidence that insects adjust their
      behaviours associated with flight, mating and foraging in response to changes in
      barometric pressure. We studied changes in different mating behaviours of three
      taxonomically unrelated insects, the curcurbit beetle, Diabrotica speciosa
      (Coleoptera), the true armyworm moth, Pseudaletia unipuncta (Lepidoptera) and the
      potato aphid, Macrosiphum euphorbiae (Hemiptera), when subjected to natural or
      experimentally manipulated changes in atmospheric pressure. In response to
      decreasing barometric pressure, male beetles exhibited decreased locomotory
      activity in a Y-tube olfactometer with female pheromone extracts. However, when
      placed in close proximity to females, they exhibited reduced courtship sequences
      and the precopulatory period. Under the same situations, females of the true
      armyworm and the potato aphid exhibited significantly reduced calling behaviour.
      Neither the movement of male beetles nor the calling of armyworm females differed
      between stable and increasing atmospheric pressure conditions. However, in the
      case of the armyworm there was a significant decrease in the incidence of mating
      under rising atmospheric conditions, suggesting an effect on male behaviour. When
      atmospheric pressure rose, very few M. euphorbiae oviparae called. This was
      similar to the situation observed under decreasing conditions, and consequently
      very little mating was observed in this species except under stable conditions.
      All species exhibited behavioural modifications, but there were interspecific
      differences related to size-related flight ability and the diel periodicity of
      mating activity. We postulate that the observed behavioral modifications,
      especially under decreasing barometric pressure would reduce the probability of
      injury or death under adverse weather conditions. 

PMID- 24098361
TI  - Perfluorooctane sulfonate disturbs Nanog expression through miR-490-3p in mouse
      embryonic stem cells.
AB  - Perfluorooctane sulfonate (PFOS) poses potential risks to reproduction and
      development. Mouse embryonic stem cells (mESCs) are ideal models for
      developmental toxicity testing of environmental contaminants in vitro. However,
      the mechanism by which PFOS affects early embryonic development is still unclear.
      In this study, mESCs were exposed to PFOS for 24 h, and then general cytotoxicity
      and pluripotency were evaluated. MTT assay showed that neither PFOS (0.2 uM, 2
      uM, 20 uM, and 200 uM) nor control medium (0.1% DMSO) treatments affected cell
      viability. Furthermore, there were no significant differences in cell cycle and
      apoptosis between the PFOS treatment and control groups. However, we found that
      the mRNA and protein levels of pluripotency markers (Sox2, Nanog) in mESCs were
      significantly decreased following exposure to PFOS for 24 h, while there were no
      significant changes in the mRNA and protein levels of Oct4. Accordingly, the
      expression levels of miR-145 and miR-490-3p, which can regulate Sox2 and Nanog
      expressions were significantly increased. Chrm2, the host gene of miR-490-3p, was
      positively associated with miR-490-3p expression after PFOS exposure. Dual
      luciferase reporter assay suggests that miR-490-3p directly targets Nanog. These
      results suggest that PFOS can disturb the expression of pluripotency factors in
      mESCs, while miR-145 and miR-490-3p play key roles in modulating this effect. 

PMID- 24098363
TI  - Variation in the form of Pavlovian conditioned approach behavior among outbred
      male Sprague-Dawley rats from different vendors and colonies: sign-tracking vs.
      goal-tracking.
AB  - Even when trained under exactly the same conditions outbred male Sprague-Dawley
      (SD) rats vary in the form of the Pavlovian conditioned approach response (CR)
      they acquire. The form of the CR (i.e. sign-tracking vs. goal-tracking) predicts
      to what degree individuals attribute incentive salience to cues associated with
      food or drugs. However, we have noticed variation in the incidence of these two
      phenotypes in rats obtained from different vendors. In this study, we quantified
      sign- and goal-tracking behavior in a reasonably large sample of SD rats obtained
      from two vendors (Harlan or Charles River), as well as from individual colonies
      operated by both vendors. Our sample of rats acquired from Harlan had, on
      average, more sign-trackers than goal-trackers, and vice versa for our sample of
      rats acquired from Charles River. Furthermore, there were significant differences
      among colonies of the same vendor. Although it is impossible to rule out
      environmental variables, SD rats at different vendors and barriers may have
      reduced phenotypic heterogeneity as a result of genetic variables, such as random
      genetic drift or population bottlenecks. Consistent with this hypothesis, we
      identified marked population structure among colonies from Harlan. Therefore,
      despite sharing the same name, investigators should be aware that important
      genetic and phenotypic differences exist among SD rats from different vendors or
      even from different colonies of the same vendor. If used judiciously this can be
      an asset to experimental design, but it can also be a pitfall for those unaware
      of the issue. 

PMID- 24098364
TI  - Host defense mechanism-based rational design of live vaccine.
AB  - Live attenuated vaccine (LAV), mimicking natural infection, provides an excellent
      protection against microbial infection. The development of LAV, however, still
      remains highly empirical and the rational design of clinically useful LAV is
      scarcely available. Apoptosis and caspase activation are general host antiviral
      responses in virus-infected cells. Utilizing these tightly regulated host defense
      mechanisms, we present a novel apoptosis-triggered attenuation of viral virulence
      as a rational design of live attenuated vaccine with desired levels of safety,
      efficacy, and productivity. Mutant influenza viruses carrying caspase recognition
      motifs in viral NP and the interferon-antagonist NS1 proteins were highly
      attenuated both in vitro and in vivo by caspase-mediated cleavage of those
      proteins in infected cells. Both viral replication and interferon-resistance were
      substantially reduced, resulting in a marked attenuation of virulence of the
      virus. Despite pronounced attenuation, the viruses demonstrated high growth
      phenotype in embryonated eggs at lower temperature, ensuring its productivity. A
      single dose vaccination with the mutant virus elicited high levels of systemic
      and mucosal antibody responses and provided complete protection against both
      homologous and heterologous lethal challenges in mouse model. While providing a
      practical means to generate seasonal or pandemic influenza live vaccines, the
      sensitization of viral proteins to pathogen-triggered apoptotic signals presents
      a potentially universal, mechanism-based rational design of live vaccines against
      many viral infections. 

PMID- 24098365
TI  - Validation of DTI tractography-based measures of primary motor area connectivity
      in the squirrel monkey brain.
AB  - Diffusion tensor imaging (DTI) tractography provides noninvasive measures of
      structural cortico-cortical connectivity of the brain. However, the agreement
      between DTI-tractography-based measures and histological 'ground truth' has not
      been quantified. In this study, we reconstructed the 3D density distribution maps
      (DDM) of fibers labeled with an anatomical tracer, biotinylated dextran amine
      (BDA), as well as DTI tractography-derived streamlines connecting the primary
      motor (M1) cortex to other cortical regions in the squirrel monkey brain. We
      evaluated the agreement in M1-cortical connectivity between the fibers labeled in
      the brain tissue and DTI streamlines on a regional and voxel-by-voxel basis. We
      found that DTI tractography is capable of providing inter-regional connectivity
      comparable to the neuroanatomical connectivity, but is less reliable measuring
      voxel-to-voxel variations within regions. 

PMID- 24098366
TI  - Staphylococcus aureus alpha toxin suppresses effective innate and adaptive immune
      responses in a murine dermonecrosis model.
AB  - An optimal host response against Staphylococcus aureus skin and soft tissue
      infections (SSTI) is dependent on IL-1beta and IL-17 mediated abscess formation.
      Alpha toxin (AT), an essential virulence factor for SSTI, has been reported to
      damage tissue integrity; however its effect on the immune response has not been
      investigated. Here, we demonstrate that infection with USA300 AT isogenic mutant
      (Deltahla), or passive immunization with an AT neutralizing mAb, 2A3, 24 h prior
      to infection with wild type USA300 (WT), resulted in dermonecrotic lesion size
      reduction, and robust neutrophil infiltration. Infiltration correlates with
      increase in proinflammatory cytokines and chemokines, as well as enhanced
      bacterial clearance relative to immunization with a negative control mAb. In
      addition, infection with Deltahla, or with WT +2A3, resulted in an early influx
      of innate IL-17(+)gammadeltaT cells and a more rapid induction of an adaptive
      immune response as measured by Th1 and Th17 cell recruitment at the site of
      infection. These results are the first direct evidence of a role for AT in
      subverting the innate and adaptive immune responses during a S. aureus SSTI.
      Further, these effects of AT can be overcome with a high affinity anti-AT mAb
      resulting in a reduction in disease severity. 

PMID- 24098367
TI  - Evidence of coat color variation sheds new light on ancient canids.
AB  - We have used a paleogenetics approach to investigate the genetic landscape of
      coat color variation in ancient Eurasian dog and wolf populations. We amplified
      DNA fragments of two genes controlling coat color, Mc1r (Melanocortin 1 Receptor)
      and CBD103 (canine-beta-defensin), in respectively 15 and 19 ancient canids (dogs
      and wolf morphotypes) from 14 different archeological sites, throughout Asia and
      Europe spanning from ca. 12 000 B.P. (end of Upper Palaeolithic) to ca. 4000 B.P.
      (Bronze Age). We provide evidence of a new variant (R301C) of the Melanocortin 1
      receptor (Mc1r) and highlight the presence of the beta-defensin melanistic
      mutation (CDB103-K locus) on ancient DNA from dog-and wolf-morphotype specimens.
      We show that the dominant K(B) allele (CBD103), which causes melanism, and R301C
      (Mc1r), the variant that may cause light hair color, are present as early as the
      beginning of the Holocene, over 10,000 years ago. These results underline the
      genetic diversity of prehistoric dogs. This diversity may have partly stemmed not
      only from the wolf gene pool captured by domestication but also from mutations
      very likely linked to the relaxation of natural selection pressure occurring in
      line with this process.

PMID- 24098368
TI  - Four common vascular endothelial growth factor polymorphisms (-2578C>A, -460C>T,
      +936C>T, and +405G>C) in susceptibility to lung cancer: a meta-analysis.
AB  - BACKGROUND AND OBJECTIVE: Vascular endothelial growth factor (VEGF) is one of the
      key initiators and regulators of angiogenesis and it plays a vital role in the
      onset and development of malignancy. The association between VEGF gene
      polymorphisms and lung cancer risk has been extensively studied in recent years,
      but currently available results remain controversial or ambiguous. The aim of
      this meta-analysis is to investigate the associations between four common VEGF
      polymorphisms (i.e., -2578C>A, -460C>T, +936C>T and +405C>G) and lung cancer
      risk. METHODS: A comprehensive search was conducted to identify all eligible
      studies to estimate the association between VEGF polymorphisms and lung cancer
      risk. Crude odds ratios (ORs) with 95% confidence intervals (CIs) were used to
      evaluate the strength of this association. RESULTS: A total of 14 published case
      control studies with 4,664 cases and 4,571 control subjects were identified. Our
      meta-analysis provides strong evidence that VEGF -2578C>A polymorphism is capable
      of increasing lung cancer susceptibility, especially among smokers and lung
      squamous cell carcinoma (SCC) patients. Additionally, for +936C>T polymorphism,
      increased lung cancer susceptibility was only observed among lung adenocarcinoma
      patients. In contrast, VEGF -460C>T polymorphism may be a protective factor among
      nonsmokers and SCC patients. Nevertheless, we did not find any association
      between +405C>G polymorphism and lung cancer risk, even when the groups were
      stratified by ethnicity, smoking status or histological type. CONCLUSION: This
      meta-analysis recommends more investigations into the relationship between 
      2578C>A and -460C>T lung cancer risks. More detailed and well-designed studies
      should be conducted to identify the causal variants and the underlying mechanisms
      of the possible associations.

PMID- 24098369
TI  - Dehydrin-like proteins in the necrotrophic fungus Alternaria brassicicola have a
      role in plant pathogenesis and stress response.
AB  - In this study, the roles of fungal dehydrin-like proteins in pathogenicity and
      protection against environmental stresses were investigated in the necrotrophic
      seed-borne fungus Alternaria brassicicola. Three proteins (called AbDhn1, AbDhn2
      and AbDhn3), harbouring the asparagine-proline-arginine (DPR) signature pattern
      and sharing the characteristic features of fungal dehydrin-like proteins, were
      identified in the A. brassicicola genome. The expression of these genes was
      induced in response to various stresses and found to be regulated by the AbHog1
      mitogen-activated protein kinase (MAPK) pathway. A knock-out approach showed that
      dehydrin-like proteins have an impact mainly on oxidative stress tolerance and on
      conidial survival upon exposure to high and freezing temperatures. The
      subcellular localization revealed that AbDhn1 and AbDhn2 were associated with
      peroxisomes, which is consistent with a possible perturbation of protective
      mechanisms to counteract oxidative stress and maintain the redox balance in AbDhn
      mutants. Finally, we show that the double deletion mutant DeltaDeltaabdhn1-abdhn2
      was highly compromised in its pathogenicity. By comparison to the wild-type, this
      mutant exhibited lower aggressiveness on B. oleracea leaves and a reduced
      capacity to be transmitted to Arabidopsis seeds via siliques. The double mutant
      was also affected with respect to conidiation, another crucial step in the
      epidemiology of the disease. 

PMID- 24098370
TI  - Suitability of pharmacokinetic models for dynamic contrast-enhanced MRI of
      abdominal aortic aneurysm vessel wall: a comparison.
AB  - PURPOSE: Increased microvascularization of the abdominal aortic aneurysm (AAA)
      vessel wall has been related to AAA progression and rupture. The aim of this
      study was to compare the suitability of three pharmacokinetic models to describe
      AAA vessel wall enhancement using dynamic contrast-enhanced magnetic resonance
      imaging (DCE-MRI). MATERIALS AND METHODS: Patients with AAA underwent DCE-MRI at
      1.5 Tesla. The volume transfer constant (K(trans) ), which reflects microvascular
      flow, permeability and surface area, was calculated by fitting the blood and
      aneurysm vessel wall gadolinium concentration curves. The relative fit errors,
      parameter uncertainties and parameter reproducibilities for the Patlak, Tofts and
      Extended Tofts model were compared to find the most suitable model. Scan-rescan
      reproducibility was assessed using the interclass correlation coefficient and
      coefficient of variation (CV). Further, the relationship between K(trans) and AAA
      size was investigated. RESULTS: DCE-MRI examinations from thirty-nine patients
      (mean age+/-SD: 72+/-6 years; M/F: 35/4) with an mean AAA maximal diameter of
      49+/-6 mm could be included for pharmacokinetic analysis. Relative fit
      uncertainties for K(trans) based on the Patlak model (17%) were significantly
      lower compared to the Tofts (37%) and Extended Tofts model (42%) (p<0.001).
      K(trans) scan-rescan reproducibility for the Patlak model (ICC = 0.61 and CV =
      22%) was comparable with the Tofts (ICC = 0.61, CV = 23%) and Extended Tofts
      model (ICC = 0.76, CV = 22%). K(trans) was positively correlated with maximal AAA
      diameter (Spearman's rho = 0.38, p = 0.02) using the Patlak model. CONCLUSION:
      Using the presented imaging protocol, the Patlak model is most suited to describe
      DCE-MRI data of the AAA vessel wall with good K(trans) scan-rescan
      reproducibility.

PMID- 24098371
TI  - Effect of subsoiling in fallow period on soil water storage and grain protein
      accumulation of dryland wheat and its regulatory effect by nitrogen application.
AB  - To provide a new way to increase water storage and retention of dryland wheat, a
      field study was conducted at Wenxi experimental site of Shanxi Agricultural
      University. The effect of subsoiling in fallow period on soil water storage,
      accumulation of proline, and formation of grain protein after anthesis were
      determined. Our results showed that subsoiling in fallow period could increase
      water storage in the 0-300 cm soil at pre-sowing stage and at anthesis stage with
      low or medium N application, especially for the 60-160 cm soil. However, the
      proline content, glutamine synthetase (GS) activity, glutamate dehydrogenase
      (GDH) activity in flag leaves and grains were all decreased by subsoiling in
      fallow period. In addition, the content of albumin, gliadin, and total protein in
      grains were also decreased while globulin content, Glu/Gli, protein yield, and
      glutelin content were increased. With N application increasing, water storage of
      soil layers from 20 to 200 cm was decreased at anthesis stage. High N application
      resulted in the increment of proline content and GS activity in grains. Besides,
      correlation analysis showed that soil storage in 40-160 cm soil was negatively
      correlated with proline content in grains; proline content in grains was
      positively correlated with GS and GDH activity in flag leaves. Contents of
      albumin, globulin and total protein in grains were positively correlated with
      proline content in grains and GDH activity in flag leaves. In conclusion,
      subsoiling in fallow period, together with N application at 150 kg.hm(-2), was
      beneficial to increase the protein yield and Glu/Gli in grains which improve the
      quality of wheat. 

PMID- 24098372
TI  - 2-Bromopalmitate reduces protein deacylation by inhibition of acyl-protein
      thioesterase enzymatic activities.
AB  - S-acylation, the covalent attachment of palmitate and other fatty acids on
      cysteine residues, is a reversible post-translational modification that exerts
      diverse effects on protein functions. S-acylation is catalyzed by protein
      acyltransferases (PAT), while deacylation requires acyl-protein thioesterases
      (APT), with numerous inhibitors for these enzymes having already been developed
      and characterized. Among these inhibitors, the palmitate analog 2-brompalmitate
      (2-BP) is the most commonly used to inhibit palmitoylation in cells.
      Nevertheless, previous results from our laboratory have suggested that 2-BP could
      affect protein deacylation. Here, we further investigated in vivo and in vitro
      the effect of 2-BP on the acylation/deacylation protein machinery, with it being
      observed that 2-BP, in addition to inhibiting PAT activity in vivo, also
      perturbed the acylation cycle of GAP-43 at the level of depalmitoylation and
      consequently affected its kinetics of membrane association. Furthermore, 2-BP was
      able to inhibit in vitro the enzymatic activities of human APT1 and APT2, the
      only two thioesterases shown to mediate protein deacylation, through an
      uncompetitive mechanism of action. In fact, APT1 and APT2 hydrolyzed both the
      monomeric form as well as the micellar state of the substrate palmitoyl-CoA. On
      the basis of the obtained results, as APTs can mediate deacylation on membrane
      bound and unbound substrates, this suggests that the access of APTs to the
      membrane interface is not a necessary requisite for deacylation. Moreover, as the
      enzymatic activity of APTs was inhibited by 2-BP treatment, then the kinetics
      analysis of protein acylation using 2-BP should be carefully interpreted, as this
      drug also inhibits protein deacylation. 

PMID- 24098373
TI  - Critical period of memory enhancement during taste avoidance conditioning in
      Lymnaea stagnalis.
AB  - The present study investigated the optimal training procedure leading to long
      lasting taste avoidance behavior in Lymnaea. A training procedure comprising 5
      repeated pairings of a conditional stimulus (CS, sucrose), with an unconditional
      stimulus (US, a tactile stimulation to the animal's head), over a 4-day period
      resulted in an enhanced memory formation than 10 CS-US repeated pairings over a 2
      day period or 20 CS-US repeated pairings on a single day. Backward conditioning
      (US-CS) pairings did not result in conditioning. Thus, this taste avoidance
      conditioning was CS-US pairing specific. Food avoidance behavior was not observed
      following training, however, if snails were immediately subjected to a cold-block
      (4 degrees C for 10 min). It was critical that the cold-block be applied within
      10 min to block long-term memory (LTM) formation. Further, exposure to the cold
      block 180 min after training also blocked both STM and LTM formation. The effects
      of the cold-block on subsequent learning and memory formation were also examined.
      We found no long lasting effects of the cold-block on subsequent memory
      formation. If protein kinase C was activated before the conditioning paradigm,
      snails could still acquire STM despite exposure to the cold-block. 

PMID- 24098374
TI  - Spatial and temporal assessment of pollen- and seed-mediated gene flow from
      genetically engineered plum Prunus domestica.
AB  - Pollen flow from a 0.46 ha plot of genetically engineered (GE) Prunus domestica
      located in West Virginia, USA was evaluated from 2000-2010. Sentinel plum trees
      were planted at distances ranging from 132 to 854 m from the center of the GE
      orchard. Plots of mixed plum varieties and seedlings were located at 384, 484 and
      998 m from the GE plot. Bee hives (Apis mellifera) were dispersed between the GE
      plum plot and the pollen flow monitoring sites. Pollen-mediated gene flow from
      out of the GE plum plot to non-GE plums under the study conditions was low, only
      occurring at all in 4 of 11 years and then in only 0.31% of the 12,116 seeds
      analyzed. When it occurred, gene flow, calculated as the number of GUS positive
      embryos/total embryos sampled, ranged from 0.215% at 132 m from the center of the
      GE plum plot (28 m from the nearest GE plum tree) to 0.033-0.017% at longer
      distances (384-998 m). Based on the percentage of GUS positive seeds per
      individual sampled tree the range was 0.4% to 12%. Within the GE field plot, gene
      flow ranged from 4.9 to 39%. Gene flow was related to distance and environmental
      conditions. A single year sample from a sentinel plot 132 m from the center of
      the GE plot accounted for 65% of the total 11-year gene flow. Spatial modeling
      indicated that gene flow dramatically decreased at distances over 400 m from the
      GE plot. Air temperature and rainfall were, respectively, positively and
      negatively correlated with gene flow, reflecting the effects of weather
      conditions on insect pollinator activity. Seed-mediated gene flow was not
      detected. These results support the feasibility of coexistence of GE and non-GE
      plum orchards. 

PMID- 24098375
TI  - CIP2A influences survival in colon cancer and is critical for maintaining Myc
      expression.
AB  - The cancerous inhibitor of protein phosphatase 2A (CIP2A) is an oncogenic factor
      that stabilises the c-Myc protein. CIP2A is overexpressed in several tumours, and
      expression levels are an independent marker for long-term outcome. To determine
      whether CIP2A expression is elevated in colon cancer and whether it might serve
      as a prognostic marker for survival, we analysed CIP2A mRNA expression by real
      time PCR in 104 colon cancer samples. CIP2A mRNA was overexpressed in colon
      cancer samples and CIP2A expression levels correlated significantly with tumour
      stage. We found that CIP2A serves as an independent prognostic marker for disease
      free and overall survival. Further, we investigated CIP2A-dependent effects on
      levels of c-Myc, Akt and on cell proliferation in three colon cancer cell lines
      by silencing CIP2A using small interfering (si) and short hairpin (sh) RNAs.
      Depletion of CIP2A substantially inhibited growth of colon cell lines and reduced
      c-Myc levels without affecting expression or function of the upstream regulatory
      kinase, Akt. Expression of CIP2A was found to be dependent on MAPK activity,
      linking elevated c-Myc expression to deregulated signal transduction in colon
      cancer. 

PMID- 24098376
TI  - Brain docosahexaenoic acid [DHA] incorporation and blood flow are increased in
      chronic alcoholics: a positron emission tomography study corrected for cerebral
      atrophy.
AB  - OBJECTIVE: Chronic alcohol dependence has been associated with disturbed
      behavior, cerebral atrophy and a low plasma concentration of docosahexaenoic acid
      (DHA, 22?6n-3), particularly if liver disease is present. In animal models,
      excessive alcohol consumption is reported to reduce brain DHA concentration,
      suggesting disturbed brain DHA metabolism. We hypothesized that brain DHA
      metabolism also is abnormal in chronic alcoholics. METHODS: We compared 15 non
      smoking chronic alcoholics, studied within 7 days of their last drink, with 22
      non-smoking healthy controls. Using published neuroimaging methods with positron
      emission tomography (PET), we measured regional coefficients (K*) and rates
      (J(in)) of DHA incorporation from plasma into the brain of each group using [1
      (11)C]DHA, and regional cerebral blood flow (rCBF) using [(15)O]water. Data were
      partial volume error corrected for brain atrophy. Plasma unesterified DHA
      concentration also was quantified. RESULTS: Mean K* for DHA was significantly and
      widely elevated by 10-20%, and rCBF was elevated by 7%-34%, in alcoholics
      compared with controls. Unesterified plasma DHA did not differ significantly
      between groups nor did whole brain J(in), the product of K* and unesterified
      plasma DHA concentration. DISCUSSION: Significantly higher values of K* for DHA
      in alcoholics indicate increased brain avidity for DHA, thus a brain DHA
      metabolic deficit vis-a-vis plasma DHA availability. Higher rCBF in alcoholics
      suggests increased energy consumption. These changes may reflect a hypermetabolic
      state related to early alcohol withdrawal, or a general brain metabolic change in
      chronic alcoholics.

PMID- 24098377
TI  - Thymoquinone inhibits tumor growth and induces apoptosis in a breast cancer
      xenograft mouse model: the role of p38 MAPK and ROS.
AB  - Due to narrow therapeutic window of cancer therapeutic agents and the development
      of resistance against these agents, there is a need to discover novel agents to
      treat breast cancer. The antitumor activities of thymoquinone (TQ), a compound
      isolated from Nigella sativa oil, were investigated in breast carcinoma in vitro
      and in vivo. Cell responses after TQ treatment were assessed by using different
      assays including MTT assay, annexin V-propidium iodide staining, Mitosox staining
      and Western blot. The antitumor effect was studied by breast tumor xenograft
      mouse model, and the tumor tissues were examined by histology and
      immunohistochemistry. The level of anti-oxidant enzymes/molecules in mouse liver
      tissues was measured by commercial kits. Here, we show that TQ induced p38
      phosphorylation and ROS production in breast cancer cells. These inductions were
      found to be responsible for TQ's anti-proliferative and pro-apoptotic effects.
      Moreover, TQ-induced ROS production regulated p38 phosphorylation but not vice
      versa. TQ treatment was found to suppress the tumor growth and this effect was
      further enhanced by combination with doxorubicin. TQ also inhibited the protein
      expression of anti-apoptotic genes, such as XIAP, survivin, Bcl-xL and Bcl-2, in
      breast cancer cells and breast tumor xenograft. Reduced Ki67 and increased TUNEL
      staining were observed in TQ-treated tumors. TQ was also found to increase the
      level of catalase, superoxide dismutase and glutathione in mouse liver tissues.
      Overall, our results demonstrated that the anti-proliferative and pro-apoptotic
      effects of TQ in breast cancer are mediated through p38 phosphorylation via ROS
      generation. 

PMID- 24098378
TI  - Analysis for distinctive activation patterns of pain and itchy in the human brain
      cortex measured using near infrared spectroscopy (NIRS).
AB  - Pain and itch are closely related sensations, yet qualitatively quite distinct.
      Despite recent advances in brain imaging techniques, identifying the differences
      between pain and itch signals in the brain cortex is difficult due to continuous
      temporal and spatial changes in the signals. The high spatial resolution of
      positron emission tomography (PET) and functional magnetic resonance imaging
      (fMRI) has substantially advanced research of pain and itch, but these are
      uncomfortable because of expensiveness, importability and the limited operation
      in the shielded room. Here, we used near infrared spectroscopy (NIRS), which has
      more conventional usability. NIRS can be used to visualize dynamic changes in
      oxygenated hemoglobin and deoxyhemoglobin concentrations in the capillary
      networks near activated neural circuits in real-time as well as fMRI. We observed
      distinct activation patterns in the frontal cortex for acute pain and histamine
      induced itch. The prefrontal cortex exhibited a pain-related and itch-related
      activation pattern of blood flow in each subject. Although it looked as though
      that activation pattern for pain and itching was different in each subject,
      further cross correlation analysis of NIRS signals between each channels showed
      an overall agreement with regard to prefrontal area involvement. As a result,
      pain-related and itch-related blood flow responses (delayed responses in
      prefrontal area) were found to be clearly different between pain (tau = +18.7
      sec) and itch (tau = +0.63 sec) stimulation. This is the first pilot study to
      demonstrate the temporal and spatial separation of a pain-induced blood flow and
      an itch-induced blood flow in human cortex during information processing. 

PMID- 24098379
TI  - Modeling the distribution of migratory bird stopovers to inform landscape-scale
      siting of wind development.
AB  - Conservation of migratory birds requires understanding the distribution of and
      potential threats to their migratory habitats. However, although migratory birds
      are protected under international treaties, few maps have been available to
      represent migration at a landscape scale useful to target conservation efforts or
      inform the siting of wind energy developments that may affect migratory birds. To
      fill this gap, we developed models that predict where four groups of birds
      concentrate or stopover during their migration through the state of Wyoming, USA:
      raptors, wetland, riparian and sparse grassland birds. The models were based on
      existing literature and expert knowledge concerning bird migration behavior and
      ecology and validated using expert ratings and known occurrences. There was
      significant agreement between migratory occurrence data and migration models for
      all groups except raptors, and all models ranked well with experts. We measured
      the overlap between the migration concentration models and a predictive model of
      wind energy development to assess the potential exposure of migratory birds to
      wind development and illustrate the utility of migratory concentration models for
      landscape-scale planning. Wind development potential is high across 15% of
      Wyoming, and 73% of this high potential area intersects important migration
      concentration areas. From 5.2% to 18.8% of each group's important migration areas
      was represented within this high wind potential area, with the highest exposures
      for sparse grassland birds and the lowest for riparian birds. Our approach could
      be replicated elsewhere to fill critical data gaps and better inform conservation
      priorities and landscape-scale planning for migratory birds. 

PMID- 24098380
TI  - Specific increase in MDR1 mediated drug-efflux in human brain endothelial cells
      following co-exposure to HIV-1 and saquinavir.
AB  - Persistence of HIV-1 reservoirs within the Central Nervous System (CNS) remains a
      significant challenge to the efficacy of potent anti-HIV-1 drugs. The primary
      human Brain Microvascular Endothelial Cells (HBMVEC) constitutes the Blood Brain
      Barrier (BBB) which interferes with anti-HIV drug delivery into the CNS. The ATP
      binding cassette (ABC) transporters expressed on HBMVEC can efflux HIV-1 protease
      inhibitors (HPI), enabling the persistence of HIV-1 in CNS. Constitutive low
      level expression of several ABC-transporters, such as MDR1 (a.k.a. P-gp) and MRPs
      are documented in HBMVEC. Although it is recognized that inflammatory cytokines
      and exposure to xenobiotic drug substrates (e.g HPI) can augment the expression
      of these transporters, it is not known whether concomitant exposure to virus and
      anti-retroviral drugs can increase drug-efflux functions in HBMVEC. Our in vitro
      studies showed that exposure of HBMVEC to HIV-1 significantly up-regulates both
      MDR1 gene expression and protein levels; however, no significant increases in
      either MRP-1 or MRP-2 were observed. Furthermore, calcein-AM dye-efflux assays
      using HBMVEC showed that, compared to virus exposure alone, the MDR1 mediated
      drug-efflux function was significantly induced following concomitant exposure to
      both HIV-1 and saquinavir (SQV). This increase in MDR1 mediated drug-efflux was
      further substantiated via increased intracellular retention of radiolabeled [(3)H
      ] SQV. The crucial role of MDR1 in (3)H-SQV efflux from HBMVEC was further
      confirmed by using both a MDR1 specific blocker (PSC-833) and MDR1 specific
      siRNAs. Therefore, MDR1 specific drug-efflux function increases in HBMVEC
      following co-exposure to HIV-1 and SQV which can reduce the penetration of HPIs
      into the infected brain reservoirs of HIV-1. A targeted suppression of MDR1 in
      the BBB may thus provide a novel strategy to suppress residual viral replication
      in the CNS, by augmenting the therapeutic efficacy of HAART drugs. 

PMID- 24098381
TI  - DNA damage repair genes controlling human papillomavirus (HPV) episome levels
      under conditions of stability and extreme instability.
AB  - DNA damage response (DDR) genes and pathways controlling the stability of HPV
      episomal DNA are reported here. We set out to understand the mechanism by which a
      DNA-binding, N-methylpyrrole-imidazole hairpin polyamide (PA25) acts to cause the
      dramatic loss of HPV DNA from cells. Southern blots revealed that PA25 alters HPV
      episomes within 5 hours of treatment. Gene expression arrays identified numerous
      DDR genes that were specifically altered in HPV16 episome-containing cells (W12E)
      by PA25, but not in HPV-negative (C33A) cells or in cells with integrated HPV16
      (SiHa). A siRNA screen of 240 DDR genes was then conducted to identify enhancers
      and repressors of PA25 activity. Serendipitously, the screen also identified many
      novel genes, such as TDP1 and TDP2, regulating normal HPV episome stability. MRN
      and 9-1-1 complexes emerged as important for PA25-mediated episome destruction
      and were selected for follow-up studies. Mre11, along with other homologous
      recombination and dsDNA break repair genes, was among the highly significant PA25
      repressors. The Mre11 inhibitor Mirin was found to sensitize HPV episomes to PA25
      resulting in a ~5-fold reduction of the PA25 IC50. A novel assay that couples end
      labeling of DNA to Q-PCR showed that PA25 causes strand breaks within HPV DNA,
      and that Mirin greatly enhances this activity. The 9-1-1 complex member Rad9, a
      representative PA25 enhancer, was transiently phosphorylated in response to PA25
      treatment suggesting that it has a role in detecting and signaling episome damage
      by PA25 to the cell. These results establish that DNA-targeted compounds enter
      cells and specifically target the HPV episome. This action leads to the
      activation of numerous DDR pathways and the massive elimination of episomal DNA
      from cells. Our findings demonstrate that viral episomes can be targeted for
      elimination from cells by minor groove binding agents, and implicate DDR pathways
      as important mediators of this process. 

PMID- 24098382
TI  - Serotonin 5-HT2A receptor activation blocks TNF-alpha mediated inflammation in
      vivo.
AB  - Tumor necrosis factor alpha (TNF-alpha) plays a key role in inflammation, and its
      production and signaling contribute to many inflammatory related diseases.
      Recently, we discovered that selective activation of serotonin 5-HT2A receptors
      with the agonist (R)-DOI produces a super-potent blockade of proinflammatory
      markers in primary rat aortic smooth muscle cells. Here, we demonstrate that
      systemic administration of (R)-DOI can block the systemic effects of TNF-alpha in
      whole animal, with potent anti-inflammatory effects in the aortic arch and small
      intestine. This includes blockade of TNF-alpha-induced expression of pro
      inflammatory cell adhesion (Icam-1, Vcam-1), cytokine (Il-6, IL-1b), and
      chemokine (Mcp-1, Cx3cl1) genes, and expression of VCAM-1 protein in the
      intestine. Further, systemic (R)-DOI also prevents the TNF-alpha-induced increase
      of circulating IL-6. Importantly, utilizing receptor selective antagonists, we
      have demonstrated that the mechanism underlying the systemic anti-inflammatory
      effects of (R)-DOI is activation of serotonin 5-HT2A receptors. Our results
      highlight a powerful new role for the serotonin 5-HT2A receptor in inflammatory
      processes, and indicate that agonism of serotonin receptors may represent an
      effective and novel approach to develop powerful small molecule therapeutics for
      inflammatory diseases and conditions such as atherosclerosis and inflammatory
      bowel disease. 

PMID- 24098383
TI  - Human F1F0 ATP synthase, mitochondrial ultrastructure and OXPHOS impairment: a
      (super-)complex matter?
AB  - Mitochondrial morphogenesis is a key process of cell physiology. It is essential
      for the proper function of this double membrane-delimited organelle, as it
      ensures the packing of the inner membrane in a very ordered pattern called
      cristae. In yeast, the mitochondrial ATP synthase is able to form dimers that can
      assemble into oligomers. Two subunits (e and g) are involved in this
      supramolecular organization. Deletion of the genes encoding these subunits has no
      effect on the ATP synthase monomer assembly or activity and only affects its
      dimerization and oligomerization. Concomitantly, the absence of subunits e and g
      and thus, of ATP synthase supercomplexes, promotes the modification of
      mitochondrial ultrastructure suggesting that ATP synthase oligomerization is
      involved in cristae morphogenesis. We report here that in mammalian cells in
      culture, the shRNA-mediated down-regulation of subunits e and g affects the
      stability of ATP synthase and results in a 50% decrease of the available
      functional enzyme. Comparable to what was shown in yeast, when subunits e and g
      expression are repressed, ATP synthase dimers and oligomers are less abundant
      when assayed by native electrophoresis. Unexpectedly, mammalian ATP synthase
      dimerization/oligomerization impairment has functional consequences on the
      respiratory chain leading to a decrease in OXPHOS activity. Finally these
      structural and functional alterations of the ATP synthase have a strong impact on
      the organelle itself leading to the fission of the mitochondrial network and the
      disorganization of mitochondrial ultrastructure. Unlike what was shown in yeast,
      the impairment of the ATP synthase oligomerization process drastically affects
      mitochondrial ATP production. Thus we propose that mutations or deletions of
      genes encoding subunits e and g may have physiopathological implications. 

PMID- 24098384
TI  - Progression, symptoms and psychosocial concerns among those severely affected by
      multiple sclerosis: a mixed-methods cross-sectional study of Black Caribbean and
      White British people.
AB  - OBJECTIVE: Multiple sclerosis is now more common among minority ethnic groups in
      the UK but little is known about their experiences, especially in advanced
      stages. We examine disease progression, symptoms and psychosocial concerns among
      Black Caribbean (BC) and White British (WB) people severely affected by MS.
      DESIGN: Mixed methods study of 43 BC and 43 WB people with MS (PwMS) with an
      Expanded Disability Status Scale (EDSS) >=6 involving data from in clinical
      records, face-to-face structured interviews and a nested-qualitative component.
      Progression Index (PI) and Multiple Sclerosis Severity Score (MSSS) were
      calculated. To control for selection bias, propensity scores were derived for
      each patient and adjusted for in the comparative statistical analysis;
      qualitative data were analysed using the framework approach. RESULTS: Median EDSS
      for both groups was (6.5; range: 6.0-9.0). Progression Index (PI) and Multiple
      Sclerosis Severity Score (MSSS) based on neurological assessment of current EDSS
      scores identified BC PwMS were more likely to have aggressive disease (PI F =
      4.04, p = 0.048, MSSS F = 10.30, p<0.001). Patients' reports of the time required
      to reach levels of functional decline equivalent to different EDSS levels varied
      by group; EDSS 4: BC 2.7 years v/s WB 10.2 years (U = 258.50, p = 0.013), EDSS
      6?6.1 years BC v/s WB 12.7 years (U = 535.500, p = 0.011), EDSS 8: BC 8.7 years
      v/s WB 10.2 years. Both groups reported high symptom burden. BC PwMS were more
      cognitively impaired than WB PwMS (F = 9.65, p = 0.003). Thematic analysis of
      qualitative interviews provides correspondence with quantitative findings; more
      BC than WB PwMS referred to feelings of extreme frustration and unresolved
      loss/confusion associated with their rapidly advancing disease. The interviews
      also reveal the centrality, meanings and impact of common MS-related symptoms.
      CONCLUSIONS: Delays in diagnosis should be avoided and more frequent reviews may
      be justified by healthcare services. Culturally acceptable interventions to
      better support people who perceive MS as an assault on identity should be
      developed to help them achieve normalisation and enhance self-identity.

PMID- 24098385
TI  - Angiotensin II signaling in human preadipose cells: participation of ERK1,2
      dependent modulation of Akt.
AB  - The renin-angiotensin system expressed in adipose tissue has been implicated in
      the modulation of adipocyte formation, glucose metabolism, triglyceride
      accumulation, lipolysis, and the onset of the adverse metabolic consequences of
      obesity. As we investigated angiotensin II signal transduction mechanisms in
      human preadipose cells, an interplay of extracellular-signal-regulated kinases 1
      and 2 (ERK1,2) and Akt/PKB became evident. Angiotensin II caused attenuation of
      phosphorylated Akt (p-Akt), at serine 473; the p-Akt/Akt ratio decreased to 0.5+/
      0.2-fold the control value without angiotensin II (p<0.001). Here we report that
      the reduction of phosphorylated Akt associates with ERK1,2 activities. In the
      absence of angiotensin II, inhibition of ERK1,2 activation with U0126 or PD98059
      resulted in a 2.1+/-0.5 (p<0.001) and 1.4+/-0.2-fold (p<0.05) increase in the p
      Akt/Akt ratio, respectively. In addition, partial knockdown of ERK1 protein
      expression by the short hairpin RNA technique also raised phosphorylated Akt in
      these cells (the p-Akt/Akt ratio was 1.5+/-0.1-fold the corresponding control;
      p<0.05). Furthermore, inhibition of ERK1,2 activation with U0126 prevented the
      reduction of p-Akt/Akt by angiotensin II. An analogous effect was found on the
      phosphorylation status of Akt downstream effectors, the forkhead box (Fox)
      proteins O1 and O4. Altogether, these results indicate that angiotensin II
      signaling in human preadipose cells involves an ERK1,2-dependent attenuation of
      Akt activity, whose impact on the biological functions under its regulation is
      not fully understood. 

PMID- 24098386
TI  - Cytokine profile in a cohort of healthy blood donors carrying polymorphisms in
      genes encoding the NLRP3 inflammasome.
AB  - BACKGROUND: The NLRP3 inflammasome has been recognized as one of the key
      components of the innate immunity by sensing a diversity of insults. Inflammasome
      activation results in the maturation of the pro-inflammatory cytokines
      interleukin (IL)-1beta and IL-18. Increased production of IL-1beta is found in
      patients with gain-of-function polymorphisms in genes encoding the NLRP3
      inflammasome. Since approximately 5% of the Swedish population are heterozygote
      carriers of these combined gene variants, their impact on inflammasome status and
      a relationship on disease development is therefore highly relevant to study. The
      present study investigates levels of inflammasome-produced cytokines as a measure
      of inflammasome activation in healthy individuals carrying Q705K polymorphism in
      the NLRP3 gene combined with C10X in the CARD8 gene. MATERIALS AND METHODS:
      Genotyping of 1006 healthy blood donors was performed for the polymorphisms Q705K
      in the NLRP3 and C10X in the CARD8 genes. IL-1beta, IL-18, IL-33, as well as a
      number of other pro-inflammatory cytokines, were analyzed by Luminex or ELISA in
      plasma from individuals carrying the polymorphisms and in age and gender matched
      non-carrier controls. RESULTS & DISCUSSION: The prevalence of the polymorphisms
      was in line with previous studies. Plasma levels of IL-1beta and IL-33 were
      elevated among carriers of combined Q705K+C10X polymorphisms compared to
      controls, whereas no difference was found for IL-18 and the other cytokines
      measured. Moreover, carriers of C10X or Q705K per se had similar plasma levels of
      IL-1beta as non-carriers. These data suggest that the combined polymorphisms
      create inflammasomes with increased basal activation state, which might provide a
      more favourable innate immune response. In spite of this, it could also represent
      the mechanisms by which the inflammatory loop is triggered into a long-term
      inflammatory phenotype.

PMID- 24098387
TI  - The antimicrobial domains of wheat puroindolines are cell-penetrating peptides
      with possible intracellular mechanisms of action.
AB  - The puroindoline proteins (PINA and PINB) of wheat display lipid-binding
      properties which affect the grain texture, a critical parameter for wheat
      quality. Interestingly, the same proteins also display antibacterial and
      antifungal properties, attributed mainly to their Tryptophan-rich domain (TRD).
      Synthetic peptides based on this domain also display selectivity towards
      bacterial and fungal cells and do not cause haemolysis of mammalian cells.
      However, the mechanisms of these activities are unclear, thus limiting our
      understanding of the in vivo roles of PINs and development of novel applications.
      This study investigated the mechanisms of antimicrobial activities of synthetic
      peptides based on the TRD of the PINA and PINB proteins. Calcein dye leakage
      tests and transmission electron microscopy showed that the peptides PuroA, Pina-M
      and Pina-W->F selectively permeabilised the large unilamellar vesicles (LUVs)
      made with negatively charged phospholipids mimicking bacterial membranes, but
      were ineffective against LUVs made with zwitterionic phospholipids mimicking
      eukaryotic membranes. Propidium iodide fluorescence tests of yeast (Saccharomyces
      cerevisiae) cells showed the peptides were able to cause loss of membrane
      integrity, PuroA and Pina-M being more efficient. Scanning electron micrographs
      of PINA-based peptide treated yeast cells showed the formation of pits or pores
      in cell membranes and release of cellular contents. Gel retardation assays
      indicated the peptides were able to bind to DNA in vitro, and the induction of
      filamental growth of E. coli cells indicated in vivo inhibition of DNA synthesis.
      Together, the results strongly suggest that the PIN-based peptides exert their
      antimicrobial effects by pore formation in the cell membrane, likely by a carpet
      like mechanism, followed by intracellular mechanisms of activity. 

PMID- 24098388
TI  - Mechanical analysis of single myocyte contraction in a 3-D elastic matrix.
AB  - BACKGROUND: Cardiac myocytes experience mechanical stress during each heartbeat.
      Excessive mechanical stresses under pathological conditions cause functional and
      structural remodeling that lead to heart diseases, yet the precise mechanisms are
      still incompletely understood. To study the cellular and molecular level
      mechanotransduction mechanisms, we developed a new 'cell-in-gel' experimental
      system to exert multiaxial (3-D) stresses on a single myocyte during active
      contraction. METHODS: Isolated myocytes are embedded in an elastic hydrogel to
      simulate the mechanical environment in myocardium (afterload). When electrically
      stimulated, the in-gel myocyte contracts while the matrix resists shortening and
      broadening of the cell, exerting normal and shear stresses on the cell. Here we
      provide a mechanical analysis, based on the Eshelby inclusion problem, of the 3-D
      strain and stress inside and outside the single myocyte during contraction in an
      elastic matrix. RESULTS: (1) The fractional shortening of the myocyte depends on
      the cell's geometric dimensions and the relative stiffness of the cell to the
      gel. A slender or softer cell has less fractional shortening. A myocyte of
      typical dimensions embedded in a gel of similar elastic stiffness can contract
      only 20% of its load-free value. (2) The longitudinal stress inside the cell is
      about 15 times the transverse stress level. (3) The traction on the cell surface
      is highly non-uniform, with a maximum near its ends, showing 'hot spots' at the
      location of intercalated disks. (4) The mechanical energy expenditure of the
      myocyte increases with the matrix stiffness in a monotonic and nonlinear manner.
      CONCLUSION: Our mechanical analyses provide analytic solutions that readily lend
      themselves to parametric studies. The resulting 3-D mapping of the strain and
      stress states serve to analyze and interpret ongoing cell-in-gel experiments, and
      the mathematical model provides an essential tool to decipher and quantify
      mechanotransduction mechanisms in cardiac myocytes.

PMID- 24098389
TI  - Phenological changes in the southern hemisphere.
AB  - Current evidence of phenological responses to recent climate change is
      substantially biased towards northern hemisphere temperate regions. Given
      regional differences in climate change, shifts in phenology will not be uniform
      across the globe, and conclusions drawn from temperate systems in the northern
      hemisphere might not be applicable to other regions on the planet. We conduct the
      largest meta-analysis to date of phenological drivers and trends among southern
      hemisphere species, assessing 1208 long-term datasets from 89 studies on 347
      species. Data were mostly from Australasia (Australia and New Zealand), South
      America and the Antarctic/subantarctic, and focused primarily on plants and
      birds. This meta-analysis shows an advance in the timing of spring events (with a
      strong Australian data bias), although substantial differences in trends were
      apparent among taxonomic groups and regions. When only statistically significant
      trends were considered, 82% of terrestrial datasets and 42% of marine datasets
      demonstrated an advance in phenology. Temperature was most frequently identified
      as the primary driver of phenological changes; however, in many studies it was
      the only climate variable considered. When precipitation was examined, it often
      played a key role but, in contrast with temperature, the direction of
      phenological shifts in response to precipitation variation was difficult to
      predict a priori. We discuss how phenological information can inform the adaptive
      capacity of species, their resilience, and constraints on autonomous adaptation.
      We also highlight serious weaknesses in past and current data collection and
      analyses at large regional scales (with very few studies in the tropics or from
      Africa) and dramatic taxonomic biases. If accurate predictions regarding the
      general effects of climate change on the biology of organisms are to be made,
      data collection policies focussing on targeting data-deficient regions and taxa
      need to be financially and logistically supported. 

PMID- 24098390
TI  - Toxicity of buprofezin on the survival of embryo and larvae of African catfish,
      Clarias gariepinus (Bloch).
AB  - Buprofezin is an insect growth regulator and widely used insecticide in Malaysia.
      The present study evaluated the toxic effects of buprofezin on the embryo and
      larvae of African catfish (Clarias gariepinus) as a model organism. The embryos
      and larvae were exposed to 7 different concentrations (0, 0.05, 0.5, 5, 25, 50
      and 100 mg/L) of buprofezin. Each concentration was assessed in five replicates.
      Eggs were artificially fertilized and 200 eggs and larvae were subjected to a
      static bath treatment for all the concentrations. The mortality of embryos was
      significantly increased with increasing buprofezin concentrations from 5 to 100
      mg/L (p< 0.05). However, the mortality was not significantly different (p<0.05)
      among the following concentrations: 0 (control), 0.05, 0.5 and 5 mg/L. Data
      obtained from the buprofezin acute toxicity tests were evaluated using probit
      analysis. The 24 h LC50 value (with 95% confidence limits) of buprofezin for
      embryos was estimated to be 6.725 (3.167-15.017) mg/L. The hatching of fish
      embryos was recorded as 68.8, 68.9, 66.9, 66.4, 26.9, 25.1 and 0.12% in response
      to 7 different concentrations of buprofezin, respectively. The mortality rate of
      larvae significantly (p<0.05) increased with increasing buprofezin concentrations
      exposed to 24-48 h. The 24 and 48 h LC50 values (with 95% confidence limits) of
      buprofezin for the larvae was estimated to be 5.702 (3.198-8.898) and 4.642
      (3.264-6.287) mg/L respectively. There were no significant differences (p>0.05)
      in the LC50 values obtained at 24 and 48 h exposure times. Malformations were
      observed when the embryos and larvae exposed to more than 5 mg/L. The results
      emerged from the study suggest that even the low concentration (5 mg/L) of
      buprofezin in the aquatic environment may have adverse effect on the early
      embryonic and larval development of African catfish. 

PMID- 24098391
TI  - The role of conspiracist ideation and worldviews in predicting rejection of
      science.
AB  - BACKGROUND: Among American Conservatives, but not Liberals, trust in science has
      been declining since the 1970's. Climate science has become particularly
      polarized, with Conservatives being more likely than Liberals to reject the
      notion that greenhouse gas emissions are warming the globe. Conversely,
      opposition to genetically-modified (GM) foods and vaccinations is often ascribed
      to the political Left although reliable data are lacking. There are also growing
      indications that rejection of science is suffused by conspiracist ideation, that
      is the general tendency to endorse conspiracy theories including the specific
      beliefs that inconvenient scientific findings constitute a "hoax."
      METHODOLOGY/PRINCIPAL FINDINGS: We conducted a propensity weighted internet-panel
      survey of the U.S. population and show that conservatism and free-market
      worldview strongly predict rejection of climate science, in contrast to their
      weaker and opposing effects on acceptance of vaccinations. The two worldview
      variables do not predict opposition to GM. Conspiracist ideation, by contrast,
      predicts rejection of all three scientific propositions, albeit to greatly
      varying extents. Greater endorsement of a diverse set of conspiracy theories
      predicts opposition to GM foods, vaccinations, and climate science. CONCLUSIONS:
      Free-market worldviews are an important predictor of the rejection of scientific
      findings that have potential regulatory implications, such as climate science,
      but not necessarily of other scientific issues. Conspiracist ideation, by
      contrast, is associated with the rejection of all scientific propositions tested.
      We highlight the manifold cognitive reasons why conspiracist ideation would stand
      in opposition to the scientific method. The involvement of conspiracist ideation
      in the rejection of science has implications for science communicators.

PMID- 24098392
TI  - Glyceryl trinitrate for prevention of post-ERCP pancreatitis and improve the rate
      of cannulation: a meta-analysis of prospective, randomized, controlled trials.
AB  - BACKGROUND: Acute pancreatitis is the most common complication of diagnostic and
      therapeutic endoscopic retrograde cholangiopancreatography (ERCP). Several
      clinical trials used glyceryl trinitrate (GTN) to prevent the incidence of post
      ERCP pancreatitis (PEP). However, the results were still controversial.
      OBJECTIVE: To conduct a meta-analysis of published, full-length, randomized
      controlled trials evaluating the effect of prophylactic GTN on the prevention of
      PEP, improve the rate of cannulation and the prevention of hyperamylasemia.
      METHODS: Literature searches were conducted using PubMed, EMBASE, The Cochrane
      Library and Web of Knowledge databases, using keywords "post-ERCP" and
      "pancreatitis" and limited in randomized controlled trials. RESULTS: Twelve RCTs
      involving 2649 patients were included. Eleven RCTs compared GTN with placebo for
      PEP prevention. Meta-analysis showed the overall incidence of PEP was
      significantly reduced by GTN treatment (RR 0.67; 95% CI, 0.52-0.87).
      Nevertheless, GTN administration did not decrease the incidence of moderate to
      severe PEP (RR 0.70; 95% CI, 0.42-1.15). Subgroup analyses revealed that GTN
      administered by sublingual was more effective than transdermal and topical in
      reducing the incidence of PEP. Besides, the prophylactic effect of GTN was far
      more obvious in the group of high PEP incidence than in the group of low PEP
      incidence. Additionally, the incidence of hyperamylasemia was significantly
      reduced by GTN treatment (RR 0.69; 95% CI, 0.54-0.90). No differences of the
      successful cannulation rate of bile ducts (RR 1.03; 95% CI, 0.99-1.06)
      attributable to GTN were observed. CONCLUSION: Prophylactic use of GTN reduced
      the overall incidence of PEP and hyperamylasemia. However, GTN was not helpful
      for the severity of PEP and the rate of cannulation.

PMID- 24098393
TI  - Human candidate polymorphisms in sympatric ethnic groups differing in malaria
      susceptibility in Mali.
AB  - Malaria still remains a major public health problem in Mali, although disease
      susceptibility varies between ethnic groups, particularly between the Fulani and
      Dogon. These two sympatric groups share similar socio-cultural factors and
      malaria transmission rates, but Fulani individuals tend to show significantly
      higher spleen enlargement scores, lower parasite prevalence, and seem less
      affected by the disease than their Dogon neighbours. We have used genetic
      polymorphisms from malaria-associated genes to investigate associations with
      various malaria metrics between the Fulanai and Dogon groups. Two cross sectional
      surveys (transmission season 2006, dry season 2007) were performed. Healthy
      volunteers from the both ethnic groups (n=939) were recruited in a rural setting.
      In each survey, clinical (spleen enlargement, axillary temperature, weight) and
      parasitological data (malaria parasite densities and species) were collected, as
      well as blood samples. One hundred and sixty six SNPs were genotyped and 5
      immunoassays (AMA1, CSP, MSP1, MSP2, total IgE) were performed on the DNA and
      serum samples respectively. The data confirm the reduced malaria susceptibility
      in the Fulani, with a higher level of the protective O-blood group, and increased
      circulating antibody levels to several malaria antigens (p<10(-15)). We
      identified SNP allele frequency differences between the 2 ethnic groups in CD36,
      IL4, RTN3 and ADCY9. Moreover, polymorphisms in FCER1A, RAD50, TNF, SLC22A4, and
      IL13 genes were correlated with antibody production (p-value<0.003). Further work
      is required to understand the mechanisms underpinning these genetic factors. 

PMID- 24098394
TI  - Transcriptome comparison of human neurons generated using induced pluripotent
      stem cells derived from dental pulp and skin fibroblasts.
AB  - Induced pluripotent stem cell (iPSC) technology is providing an opportunity to
      study neuropsychiatric disorders through the capacity to grow patient-specific
      neurons in vitro. Skin fibroblasts obtained by biopsy have been the most reliable
      source of cells for reprogramming. However, using other somatic cells obtained by
      less invasive means would be ideal, especially in children with autism spectrum
      disorders (ASD) and other neurodevelopmental conditions. In addition to
      fibroblasts, iPSCs have been developed from cord blood, lymphocytes, hair
      keratinocytes, and dental pulp from deciduous teeth. Of these, dental pulp would
      be a good source for neurodevelopmental disorders in children because obtaining
      material is non-invasive. We investigated its suitability for disease modeling by
      carrying out gene expression profiling, using RNA-seq, on differentiated neurons
      derived from iPSCs made from dental pulp extracted from deciduous teeth (T-iPSCs)
      and fibroblasts (F-iPSCs). This is the first RNA-seq analysis comparing gene
      expression profiles in neurons derived from iPSCs made from different somatic
      cells. For the most part, gene expression profiles were quite similar with only
      329 genes showing differential expression at a nominally significant p-value
      (p<0.05), of which 63 remained significant after correcting for genome-wide
      analysis (FDR <0.05). The most striking difference was the lower level of
      expression detected for numerous members of the all four HOX gene families in
      neurons derived from T-iPSCs. In addition, an increased level of expression was
      seen for several transcription factors expressed in the developing forebrain
      (FOXP2, OTX1, and LHX2, for example). Overall, pathway analysis revealed that
      differentially expressed genes that showed higher levels of expression in neurons
      derived from T-iPSCs were enriched for genes implicated in schizophrenia (SZ).
      The findings suggest that neurons derived from T-iPSCs are suitable for disease
      modeling neuropsychiatric disorder and may have some advantages over those
      derived from F-iPSCs. 

PMID- 24098395
TI  - A two-stage model for in vivo assessment of brain tumor perfusion and abnormal
      vascular structure using arterial spin labeling.
AB  - The ability to assess brain tumor perfusion and abnormalities in the vascular
      structure in vivo could provide significant benefits in terms of lesion diagnosis
      and assessment of treatment response. Arterial spin labeling (ASL) has emerged as
      an increasingly viable methodology for non-invasive assessment of perfusion.
      Although kinetic models have been developed to describe perfusion in healthy
      tissue, the dynamic behaviour of the ASL signal in the brain tumor environment
      has not been extensively studied. We show here that dynamic ASL data acquired in
      brain tumors displays an increased level of 'biphasic' behaviour, compared to
      that seen in healthy tissue. A new two-stage model is presented which more
      accurately describes this behaviour, and provides measurements of perfusion, pre
      capillary blood volume fraction and transit time, and capillary bolus arrival
      time. These biomarkers offer a novel contrast in the tumor and surrounding
      tissue, and provide a means for measuring tumor perfusion and vascular structural
      abnormalities in a fully non-invasive manner. 

PMID- 24098396
TI  - Neural mechanisms underlying breathing complexity.
AB  - Breathing is maintained and controlled by a network of automatic neurons in the
      brainstem that generate respiratory rhythm and receive regulatory inputs.
      Breathing complexity therefore arises from respiratory central pattern generators
      modulated by peripheral and supra-spinal inputs. Very little is known on the
      brainstem neural substrates underlying breathing complexity in humans. We used
      both experimental and theoretical approaches to decipher these mechanisms in
      healthy humans and patients with chronic obstructive pulmonary disease (COPD).
      COPD is the most frequent chronic lung disease in the general population mainly
      due to tobacco smoke. In patients, airflow obstruction associated with
      hyperinflation and respiratory muscles weakness are key factors contributing to
      load-capacity imbalance and hence increased respiratory drive. Unexpectedly, we
      found that the patients breathed with a higher level of complexity during
      inspiration and expiration than controls. Using functional magnetic resonance
      imaging (fMRI), we scanned the brain of the participants to analyze the activity
      of two small regions involved in respiratory rhythmogenesis, the rostral ventro
      lateral (VL) medulla (pre-Botzinger complex) and the caudal VL pons (parafacial
      group). fMRI revealed in controls higher activity of the VL medulla suggesting
      active inspiration, while in patients higher activity of the VL pons suggesting
      active expiration. COPD patients reactivate the parafacial to sustain
      ventilation. These findings may be involved in the onset of respiratory failure
      when the neural network becomes overwhelmed by respiratory overload We show that
      central neural activity correlates with airflow complexity in healthy subjects
      and COPD patients, at rest and during inspiratory loading. We finally used a
      theoretical approach of respiratory rhythmogenesis that reproduces the kernel
      activity of neurons involved in the automatic breathing. The model reveals how a
      chaotic activity in neurons can contribute to chaos in airflow and reproduces key
      experimental fMRI findings. 

PMID- 24098397
TI  - Closing the gap between the inside and the outside: interoceptive sensitivity and
      social distances.
AB  - Humans' ability to represent their body state from within through interoception
      has been proposed to predict different aspects of human cognition and behaviour.
      We focused on the possible contribution of interoceptive sensitivity to social
      behaviour as mediated by adaptive modulation of autonomic response. We, thus,
      investigated whether interoceptive sensitivity to one's heartbeat predicts
      participants' autonomic response at different social distances. We measured
      respiratory sinus arrhythmia (RSA) during either a Social or a Non-social task.
      In the Social task each participant viewed an experimenter performing a caress
      like movement at different distances from their hand. In the Non-social task a
      metal stick was moved at the same distances from the participant's hand. We found
      a positive association between interoceptive sensitivity and autonomic response
      only for the social setting. Moreover, only good heartbeat perceivers showed
      higher autonomic response 1) in the social compared to the non-social setting, 2)
      specifically, when the experimenter's hand was moving at boundary of their
      peripersonal space (20 cm from the participant's hand). Our findings suggest that
      interoceptive sensitivity might contribute to interindividual differences
      concerning social attitudes and interpersonal space representation via
      recruitment of different adaptive autonomic response strategies. 

PMID- 24098398
TI  - Different distribution of HIV-1 subtype and drug resistance were found among
      treatment naive individuals in Henan, Guangxi, and Yunnan province of China.
AB  - Yunnan, Guangxi and Henan are the provinces with the most severe HIV epidemic in
      China, which were also among the first group of areas providing free ART in 2004.
      However, little comprehensive data are available on prevalence of HIV subtype and
      baseline drug resistance in drug-naive populations. In this study, 1746 treatment
      naive HIV-positive individuals were randomly selected from new-reported cases in
      Henan, Guangxi and Yunnan. Among of them, subtypes and drug resistance of 1159
      strains were determined by amplifying and sequencing full-length pol genes.
      Significantly different distributions of HIV subtypes prevalent in three
      provinces were identified (P<0.01). CRF08_BC was found dominant in Yunnan
      (59.8%), while CRF01_AE was dominant in Guangxi (77.3%) and subtype B was
      dominant in Henan province (93.9%). The total prevalence of drug resistance was
      7.1%. The highest prevalence of HIV drug resistance was found in Henan (12.2%),
      followed by Yunnan (5.6%) and Guangxi (3.3%). The results of this study suggest
      that genetic drug-resistance should be tested before initiation of ART in China,
      especially in Henan province. Furthermore, the prevalence of HIV drug resistant
      strains should be considered separately in different areas in China before the
      change of different free ART regimens. 

PMID- 24098399
TI  - Stat3 inhibition attenuates mechanical allodynia through transcriptional
      regulation of chemokine expression in spinal astrocytes.
AB  - BACKGROUND: Signal transducer and activator of transcription 3 (Stat3) is known
      to induce cell proliferation and inflammation by regulating gene transcription.
      Recent studies showed that Stat3 modulates nociceptive transmission by reducing
      spinal astrocyte proliferation. However, it is unclear whether Stat3 also
      contributes to the modulation of nociceptive transmission by regulating
      inflammatory response in spinal astrocytes. This study aimed at investigating the
      role of Stat3 on neuroinflammation during development of pain in rats after
      intrathecal injection of lipopolysaccharide (LPS). METHODS: Stat3 specific siRNA
      oligo and synthetic selective inhibitor (Stattic) were applied to block the
      activity of Stat3 in primary astrocytes or rat spinal cord, respectively. LPS was
      used to induce the expression of proinflammatory genes in all studies.
      Immunofluorescence staining of cells and slices of spinal cord was performed to
      monitor Stat3 activation. The impact of Stat3 inhibition on proinflammatory genes
      expression was determined by cytokine antibody array, enzyme-linked immunosorbent
      assay and real-time polymerase chain reaction. Mechanical allodynia, as
      determined by the threshold pressure that could induce hind paw withdrawal after
      application of standardized von Frey filaments, was used to detect the effects of
      Stat3 inhibition after pain development with intrathecal LPS injection. RESULTS:
      Intrathecal injection of LPS activated Stat3 in reactive spinal astrocytes.
      Blockade of Stat3 activity attenuated mechanical allodynia significantly and was
      correlated with a lower number of reactive astrocytes in the spinal dorsal horn.
      In vitro study demonstrated that Stat3 modulated inflammatory response in primary
      astrocytes by transcriptional regulation of chemokine expression including
      Cx3cl1, Cxcl5, Cxcl10 and Ccl20. Similarly, inhibition of Stat3 reversed the
      expression of these chemokines in the spinal dorsal horn. CONCLUSIONS: Stat3
      acted as a transcriptional regulator of reactive astrocytes by modulating
      chemokine expression. Stat3 regulated inflammatory response in astrocytes and
      contributed to pain modulation. Blockade of Stat3 represents a new target for
      pain control.

PMID- 24098400
TI  - Molecular cloning, characterization and expression profiling of a ryanodine
      receptor gene in Asian corn borer, Ostrinia furnacalis (Guenee).
AB  - Ryanodine receptor (RyR) Ca(2+) release channel is the target of diamide
      insecticides, which show selective insecticidal activity against lepidopterous
      insects. To study the molecular mechanisms underlying the species-specific action
      of diamide insecticides, we have cloned and characterized the entire cDNA
      sequence of RyR from Ostrinia furnacalis (named as OfRyR). The OfRyR mRNA has an
      Open Reading Frame of 15324 bp nucleotides and encodes a 5108 amino acid
      polypeptide that displays 79-97% identity with other insects RyR proteins and
      shows the greatest identity with Cnaphalocrocis medinalis RyR (97%). Quantitative
      real-time PCR showed that the OfRyR was expressed at the lowest level in egg and
      the highest level in adult. The relative expression level of OfRyR in first,
      third and fifth-instar larva were 1.28, 1.19 and 1.99 times of that in egg.
      Moreover, two alternative splicing sites were identified in the OfRyR gene. One
      pair of mutually exclusive exons (a/b) were present in the central part of the
      predicted SPRY domain, and an optional exon (c) was located between the third and
      fourth RyR domains. Diagnostic PCR demonstrated that exons a and b existed in all
      developmental stages of OfRyR cDNA, but exon c was not detected in the egg cDNA.
      And the usage frequencies of these exons showed a significant difference between
      different developmental stages. These results provided the crucial basis for the
      functional expression of OfRyR and for the discovery of compound with potentially
      selective insect activtity. 

PMID- 24098401
TI  - Associations of ACE gene insertion/deletion polymorphism, ACE activity, and ACE
      mRNA expression with hypertension in a Chinese population.
AB  - BACKGROUND: The present study was designed to explore the association of
      angiotensin converting enzyme (ACE) gene insertion/deletion (I/D, rs4646994)
      polymorphism, plasma ACE activity, and circulating ACE mRNA expression with
      essential hypertension (EH) in a Chinese population. In addition, a new detection
      method for circulating ACE mRNA expression was explored. METHODS: The research
      was approved by the ethics committee of Zhejiang Provincial Center for Disease
      Prevention and Control. Written informed consent was obtained prior to the
      investigation. 221 hypertensives (cases) and 221 normotensives (controls) were
      interviewed, subjected to a physical examination, and provided blood for
      biochemical and genetic tests. The ACE mRNA expression was analyzed by real time
      fluorescent quantitative Reverse Transcription PCR (FQ-RT-PCR). We performed
      logistic regression to assess associations of ACE I/D genotypes, ACE activity,
      and ACE mRNA expression levels with hypertension. RESULTS: The results of the
      multivariate logistic regression analysis showed that the additive model (ID, DD
      versus II) of the ACE genotype revealed an association with hypertension with
      adjusted OR of 1.43(95% CI: 1.04-1.97), and ACE ID genotype with adjusted OR of
      1.72(95% CI: 1.01-2.92), DD genotype with adjusted OR of 1.94(95% CI: 1.01-3.73),
      respectively. In addition, our data also indicate that plasma ACE activity
      (adjusted OR was 1.13(95% CI: 1.08-1.18)) was significantly related to
      hypertension. However, the plasma ACE mRNA expressions were not different between
      the cases and controls. CONCLUSION: ACE I/D polymorphism and ACE activity
      revealed significant influence on hypertension, while circulating ACE mRNA
      expression was not important factors associated with hypertension in this Chinese
      population. The detection of circulating ACE mRNA expression by FQ-RT-PCR might
      be a useful method for early screening and monitoring of EH.

PMID- 24098403
TI  - Fire and brimstone: the microbially mediated formation of elemental sulfur
      nodules from an isotope and major element study in the paleo-Dead Sea.
AB  - We present coupled sulfur and oxygen isotope data from sulfur nodules and
      surrounding gypsum, as well as iron and manganese concentration data, from the
      Lisan Formation near the Dead Sea (Israel). The sulfur isotope composition in the
      nodules ranges between -9 and -110/00, 27 to 290/00 lighter than the surrounding
      gypsum, while the oxygen isotope composition of the gypsum is constant around
      240/00. The constant sulfur isotope composition of the nodule is consistent with
      formation in an 'open system'. Iron concentrations in the gypsum increase toward
      the nodule, while manganese concentrations decrease, suggesting a redox boundary
      at the nodule-gypsum interface during aqueous phase diagenesis. We propose that
      sulfur nodules in the Lisan Formation are generated through bacterial sulfate
      reduction, which terminates at elemental sulfur. We speculate that the sulfate
      saturated pore fluids, coupled with the low availability of an electron donor,
      terminates the trithionate pathway before the final two-electron reduction,
      producing thionites, which then disproportionate to form abundant elemental
      sulfur. 

PMID- 24098402
TI  - Ischemic postconditioning-mediated miRNA-21 protects against cardiac
      ischemia/reperfusion injury via PTEN/Akt pathway.
AB  - BACKGROUND: Ischemic postconditioning (IPost) protects the reperfused heart from
      infarction which has drawn much attention recently. However, studies to date have
      rarely investigated the role of microRNAs (miRNAs) in IPost. The aims of this
      study were to investigate whether miR-21 is involved in the protective effect of
      IPost against myocardial ischemia-reperfusion (I/R) injury and disclose the
      potential molecular mechanisms involved. METHODS AND RESULTS: We found that miR
      21 was remarkably up-regulated in mouse hearts after IPost. To determine the
      protective role of IPost-induced miR-21 up-regulation, the mice were divided into
      the following four groups: I/R group; I/R+IPost group (I/R mice treated with
      IPost); Antagomir-21+IPost+I/R group (I/R mice treated with anagomir-21 and
      IPost); Scramble+IPost+I/R group (I/R mice treated with scramble and IPost). The
      results showed IPost could reduce I/R injury-induced infarct size of the left
      ventricle, improve cardiac function, and prevent myocardial apoptosis, while
      knockdown of miR-21 with antagomir-21 could reverse these protective effects of
      IPost against mouse I/R injury. Furthermore, we confirmed that miR-21 plays a
      protective role in myocardial apoptosis through PTEN/Akt signaling pathway, which
      was abrogated by the PI3K inhibitor LY294002. The protective effect of miR-21 on
      myocardial apoptosis was further revealed in mouse hearts after IPost treatment
      in vivo. CONCLUSIONS: Our data clearly demonstrate that miR-21 is involved in
      IPost-mediated cardiac protection against I/R injury and dysfunction through the
      PTEN/Akt signaling pathway in vivo. Identifying the beneficial roles of IPost
      regulated miRNAs in cardiac protection, which may be a rational target selection
      for ischemic cardioprotection.

PMID- 24098404
TI  - Quantitative proteomic analysis of gingival crevicular fluid in different
      periodontal conditions.
AB  - AIM: To quantify the proteome composition of the GCF in periodontal health (HH)
      and in sites with different clinical conditions in chronic periodontitis (CP)
      subjects. MATERIAL AND METHODS: 5 subjects with HH and 5 with CP were submitted
      to full-mouth periodontal examination, and GCF sampling. Sites in the CP group
      were classified and sampled as periodontitis (P, probing depth, PD>4 mm),
      gingivitis (G, PD<=3 mm with bleeding on probing, BOP), and healthy sites (H,
      PD<=3 mm without BOP). GCF proteins were subjected to liquid chromatography
      electrospray ionization mass spectrometry for identification, characterization
      and quantification. RESULTS: 230 proteins were identified; 145 proteins were
      detected in HH, 214 in P, 154 in G, and 133 in H. Four proteins were exclusively
      detected at HH, 43 proteins at P, 7 proteins at G, and 1 protein at H. Compared
      to HH group, 35 and 6 proteins were more abundant in P and G (p<0.001),
      respectively; and 4, 15 and 37 proteins were less abundant in P, G and H
      (p<=0.01), respectively. CONCLUSIONS: There are marked differences in the GCF
      proteome according to disease profile. Comprehension of the role of the
      identified proteins in the etiopathogenesis of periodontal disease may lead to
      biomarkers definition.

PMID- 24098405
TI  - Effect of hepatitis C infection on HIV-induced apoptosis.
AB  - BACKGROUND: Hepatitis C virus (HCV) coinfection was reported to negatively affect
      HIV disease and HIV infection has a deleterious effect on HCV-related liver
      disease. However, despite common occurrence of HCV/HIV coinfection little is
      known about the mechanisms of interactions between the two viruses. METHODS: We
      studied CD4+ and CD8+ T cell and CD19+ B cell apoptosis in 104 HIV-positive
      patients (56 were also HCV-positive) and in 22 HCV/HIV-coinfected patients
      treated for chronic hepatitis C with pegylated interferon and ribavirin. We also
      analyzed HCV/HIV coinfection in a Daudi B-cell line expressing CD4 and
      susceptible to both HCV and HIV infection. Apoptosis was measured by AnnexinV
      staining. RESULTS: HCV/HIV coinfected patients had lower CD4+ and CD8+ T cell
      apoptosis and higher CD19+ B cell apoptosis than those with HIV monoinfection.
      Furthermore, anti-HCV treatment of HCV/HIV coinfected patients was followed by an
      increase of CD4+ and CD8+ T cell apoptosis and a decrease of CD19+ B cell
      apoptosis. In the Daudi CD4+ cell line, presence of HCV infection facilitated HIV
      replication, however, decreased the rate of HIV-related cell death. CONCLUSION:
      In HCV/HIV coinfected patients T-cells were found to be destroyed at a slower
      rate than in HIV monoinfected patients. These results suggest that HCV is a
      molecular-level determinant in HIV disease.

PMID- 24098406
TI  - A systematic review and meta-analysis of the global seasonality of norovirus.
AB  - BACKGROUND: Noroviruses are the most common cause of acute gastroenteritis across
      all ages worldwide. These pathogens are generally understood to exhibit a
      wintertime seasonality, though a systematic assessment of seasonal patterns has
      not been conducted in the era of modern diagnostics. METHODS: We conducted a
      systematic review of the Pubmed Medline database for articles published between
      1997 and 2011 to identify and extract data from articles reporting on monthly
      counts of norovirus. We conducted a descriptive analysis to document seasonal
      patterns of norovirus disease, and we also constructed multivariate linear models
      to identify factors associated with the strength of norovirus seasonality.
      RESULTS: The searched identified 293 unique articles, yielding 38 case and 29
      outbreak data series. Within these data series, 52.7% of cases and 41.2% of
      outbreaks occurred in winter months, and 78.9% of cases and 71.0% of outbreaks
      occurred in cool months. Both case and outbreak studies showed an earlier peak in
      season-year 2002-03, but not in season-year 2006-07, years when new genogroup II
      type 4 variants emerged. For outbreaks, norovirus season strength was positively
      associated with average rainfall in the wettest month, and inversely associated
      with crude birth rate in both bivariate and multivariate analyses. For cases,
      none of the covariates examined was associated with season strength. When case
      and outbreaks were combined, average rainfall in the wettest month was positively
      associated with season strength. CONCLUSIONS: Norovirus is a wintertime
      phenomenon, at least in the temperate northern hemisphere where most data are
      available. Our results point to possible associations of season strength with
      rain in the wettest month and crude birth rate.

PMID- 24098408
TI  - Food prices and consumer demand: differences across income levels and ethnic
      groups.
AB  - BACKGROUND: Targeted food pricing policies may improve population diets. To
      assess their effects on inequalities, it is important to determine responsiveness
      to price changes across income levels and ethnic groups. OBJECTIVE: Our goal was
      to estimate price elasticity (PE) values for major commonly consumed food groups
      in New Zealand, by income and ethnicity. PE values represent percentage change in
      demand associated with 1% change in price of that good (own-PE) or another good
      (cross-PE). DESIGN: We used food expenditure data from national household
      economic surveys in 2007/08 and 2009/10 and Food Price Index data from 2007 and
      2010. Adopting an Almost Ideal Demand System approach, own-PE and cross-PE
      estimates were derived for 24 food categories, household income quintiles, and
      two ethnic groups (Maori and non-Maori). RESULTS: Own-PE estimates (with two
      exceptions) ranged from -0.44 to -1.78. Cross-PE estimates were generally small;
      only 31% of absolute values were greater than 0.10. Excluding the outlier 'energy
      drinks', nine of 23 food groups had significantly stronger own-PEs for the lowest
      versus highest income quintiles (average regression-based difference across food
      groups -0.30 (95% CI -0.62 to 0.02)). Six own-PEs were significantly stronger
      among Maori; the average difference for Maori: non-Maori across food groups was 
      0.26 (95% CI -0.52 to 0.00). CONCLUSIONS: Food pricing policies have potential to
      improve population diets. The greater sensitivity of low-income households and
      Maori to price changes suggests the beneficial effects of such policies on health
      would be greatest for these groups.

PMID- 24098407
TI  - Biodegradation of the allelopathic chemical m-tyrosine by Bacillus aquimaris SSC5
      involves the homogentisate central pathway.
AB  - m-Tyrosine is an amino acid analogue, exuded from the roots of fescue grasses,
      which acts as a potent allelopathic and a broad spectrum herbicidal chemical.
      Although the production and toxic effects of m-tyrosine are known, its microbial
      degradation has not been documented yet. A soil microcosm study showed efficient
      degradation of m-tyrosine by the inhabitant microorganisms. A bacterial strain
      designated SSC5, that was able to utilize m-tyrosine as the sole source of
      carbon, nitrogen, and energy, was isolated from the soil microcosm and was
      characterized as Bacillus aquimaris. Analytical methods such as HPLC, GC-MS, and
      (1)H-NMR performed on the resting cell samples identified the formation of 3
      hydroxyphenylpyruvate (3-OH-PPA), 3-hydroxyphenylacetate (3-OH-PhAc), and
      homogentisate (HMG) as major intermediates in the m-tyrosine degradation pathway.
      Enzymatic assays carried out on cell-free lysates of m-tyrosine-induced cells
      confirmed transamination reaction as the first step of m-tyrosine degradation.
      The intermediate 3-OH-PhAc thus obtained was further funneled into the HMG
      central pathway as revealed by a hydroxylase enzyme assay. Subsequent degradation
      of HMG occurred by ring cleavage catalyzed by the enzyme homogentisate 1, 2
      dioxygenase. This study has significant implications in terms of understanding
      the environmental fate of m-tyrosine as well as regulation of its phytotoxic
      effect by soil microorganisms. 

PMID- 24098409
TI  - The imaginary part of coherency in autism: differences in cortical functional
      connectivity in preschool children.
AB  - Cognition arises from the transient integration and segregation of activity
      across functionally distinct brain areas. Autism Spectrum Disorders (ASD), which
      encompass a wide range of developmental disabilities, have been presumed to be
      associated with a problem in cortical and sub-cortical dynamics of coordinated
      activity, often involving enhanced local but decreased long range coordination
      over areas of integration. In this paper we challenge this idea by presenting
      results from a relatively large population of ASD children and age-matched
      controls during a face-processing task. Over most of the explored domain,
      children with ASD exhibited enhanced synchronization, although finer detail
      reveals specific enhancement/reduction of synchrony depending on time, frequency
      and brain site. Our results are derived from the use of the imaginary part of
      coherency, a measure which is not susceptible to volume conduction artifacts and
      therefore presents a credible picture of coordinated brain activity. We also
      present evidence that this measure is a good candidate to provide features in
      building a classifier to be used as a potential biomarker for autism. 

PMID- 24098410
TI  - Liver ischemic preconditioning (IPC) improves intestinal microbiota following
      liver transplantation in rats through 16s rDNA-based analysis of microbial
      structure shift.
AB  - BACKGROUND: Ischemia-reperfusion (I/R) injury is associated with intestinal
      microbial dysbiosis. The "gut-liver axis" closely links gut function and liver
      function in health and disease. Ischemic preconditioning (IPC) has been proven to
      reduce I/R injury in the surgery. This study aims to explore the effect of IPC on
      intestinal microbiota and to analyze characteristics of microbial structure shift
      following liver transplantation (LT). METHODS: The LT animal models of liver and
      gut IPC were established. Hepatic graft function was assessed by histology and
      serum ALT/AST. Intestinal barrier function was evaluated by mucosal
      ultrastructure, serum endotoxin, bacterial translocation, fecal sIgA content and
      serum TNF-alpha. Intestinal bacterial populations were determined by quantitative
      PCR. Microbial composition was characterized by DGGE and specific bacterial
      species were determined by sequence analysis. PRINCIPAL FINDINGS: Liver IPC
      improved hepatic graft function expressed as ameliorated graft structure and
      reduced ALT/AST levels. After administration of liver IPC, intestinal mucosal
      ultrastructure improved, serum endotoxin and bacterial translocation mildly
      decreased, fecal sIgA content increased, and serum TNF-alpha decreased. Moreover,
      liver IPC promoted microbial restorations mainly through restoring
      Bifidobacterium spp., Clostridium clusters XI and Clostridium cluster XIVab on
      bacterial genus level. DGGE profiles indicated that liver IPC increased microbial
      diversity and species richness, and cluster analysis demonstrated that microbial
      structures were similar and clustered together between the NC group and Liver-IPC
      group. Furthermore, the phylogenetic tree of band sequences showed key bacteria
      corresponding to 10 key band classes of microbial structure shift induced by
      liver IPC, most of which were assigned to Bacteroidetes phylum. CONCLUSION: Liver
      IPC cannot only improve hepatic graft function and intestinal barrier function,
      but also promote restorations of intestinal microbiota following LT, which may
      further benefit hepatic graft by positive feedback of the "gut-liver axis".

PMID- 24098411
TI  - Natural variation of the RICE FLOWERING LOCUS T 1 contributes to flowering time
      divergence in rice.
AB  - In rice (Oryza sativa L.), there is a diversity in flowering time that is
      strictly genetically regulated. Some indica cultivars show extremely late
      flowering under long-day conditions, but little is known about the gene(s)
      involved. Here, we demonstrate that functional defects in the florigen gene RFT1
      are the main cause of late flowering in an indica cultivar, Nona Bokra. Mapping
      and complementation studies revealed that sequence polymorphisms in the RFT1
      regulatory and coding regions are likely to cause late flowering under long-day
      conditions. We detected polymorphisms in the promoter region that lead to reduced
      expression levels of RFT1. We also identified an amino acid substitution (E105K)
      that leads to a functional defect in Nona Bokra RFT1. Sequencing of the RFT1
      region in rice accessions from a global collection showed that the E105K mutation
      is found only in indica, and indicated a strong association between the RFT1
      haplotype and extremely late flowering in a functional Hd1 background.
      Furthermore, SNPs in the regulatory region of RFT1 and the E105K substitution in
      1,397 accessions show strong linkage disequilibrium with a flowering time
      associated SNP. Although the defective E105K allele of RFT1 (but not of another
      florigen gene, Hd3a) is found in many cultivars, relative rate tests revealed no
      evidence for differential rate of evolution of these genes. The ratios of
      nonsynonymous to synonymous substitutions suggest that the E105K mutation
      resulting in the defect in RFT1 occurred relatively recently. These findings
      indicate that natural mutations in RFT1 provide flowering time divergence under
      long-day conditions. 

PMID- 24098412
TI  - Evidence for introduction bottleneck and extensive inter-gene pool (Mesoamerica x
      Andes) hybridization in the European common bean (Phaseolus vulgaris L.)
      germplasm.
AB  - Common bean diversity within and between Mesoamerican and Andean gene pools was
      compared in 89 landraces from America and 256 landraces from Europe, to elucidate
      the effects of bottleneck of introduction and selection for adaptation during the
      expansion of common bean (Phaseolus vulgaris L.) in Europe. Thirteen highly
      polymorphic nuclear microsatellite markers (nuSSRs) were used to complement
      chloroplast microsatellite (cpSSRs) and nuclear markers (phaseolin and Pv
      shatterproof1) data from previous studies. To verify the extent of the
      introduction bottleneck, inter-gene pool hybrids were distinguished from "pure"
      accessions. Hybrids were identified on the basis of recombination of gene pool
      specific cpSSR, phaseolin and Pv-shatterproof1 markers with a Bayesian
      assignments based on nuSSRs, and with STRUCTURE admixture analysis. More hybrids
      were detected than previously, and their frequency was almost four times larger
      in Europe (40.2%) than in America (12.3%). The genetic bottleneck following the
      introduction into Europe was not evidenced in the analysis including all the
      accessions, but it was significant when estimated only with "pure" accessions,
      and five times larger for Mesoamerican than for Andean germplasm. The extensive
      inter-gene pool hybridization generated a large amount of genotypic diversity
      that mitigated the effects of the bottleneck that occurred when common bean was
      introduced in Europe. The implication for evolution and the advantages for common
      bean breeding are discussed. 

PMID- 24098413
TI  - Innate immune response of alveolar macrophage to house dust mite allergen is
      mediated through TLR2/-4 co-activation.
AB  - House dust mite, Dermatophagoides pteronyssinus (Der p), is one of the major
      allergens responsible for allergic asthma. However, the putative receptors
      involved in the signalization of Der p to the innate immune cells are still
      poorly defined as well as the impact of their activation on the outcome of the
      allergen-induced cell response. We previously reported that the HDM activation of
      mouse alveolar macrophages (AM) involves the TLR4/CD14 cell surface receptor
      complex. Here using a TLR ligand screening essay, we demonstrate that HDM protein
      extract engages the TLR2, in addition to the TLR4, in engineered TLR-transfected
      HEK cells but also in the MH-S mouse alveolar macrophage cell line model.
      Moreover we found that the concomitant recruitment of the MH-S cell's TLR2 and
      TLR4 receptors by the HDM extract activates the MyD88-dependent signaling pathway
      and leads to the secretion of the NF-kappaB regulated pro-inflammatory factors NO
      and TNF-alpha. However unlike with the canonical TLR4 ligand (i.e. the bacterial
      LPS) mobilization of TLR4 by the HDM extract induces a reduced production of the
      IL-12 pro-inflammatory cytokine and fails to trigger the expression of the T-bet
      transcription factor. Finally we demonstrated that HDM extract down-regulates LPS
      induced IL-12 and T-bet expression through a TLR2 dependent mechanism. Therefore,
      we propose that the simultaneous engagement of the TLR2 and TLR4 receptors by the
      HDM extract results in a cross regulated original activation pattern of the AM
      which may contribute to the Th2 polarization of the allergen-induced immune
      response. The deciphering of these cross-regulation networks is of prime
      importance to open the way for original therapeutic strategies taking advantage
      of these receptors and their associated signaling pathways to treat allergic
      asthma. 

PMID- 24098415
TI  - A novel alkaloid from marine-derived actinomycete Streptomyces xinghaiensis with
      broad-spectrum antibacterial and cytotoxic activities.
AB  - Due to the increasing emergence of drug-resistant bacteria and tumor cell lines,
      novel antibiotics with antibacterial and cytotoxic activities are urgently
      needed. Marine actinobacteria are rich sources of novel antibiotics, and here we
      report the discovery of a novel alkaloid, xinghaiamine A, from a marine-derived
      actinomycete Streptomyces xinghaiensis NRRL B24674(T). Xinghaiamine A was
      purified from the fermentation broth, and its structure was elucidated based on
      extensive spectroscopic analysis, including 1D and 2D NMR spectrum as well as
      mass spectrometry. Xinghaiamine A was identified to be a novel alkaloid with
      highly symmetric structure on the basis of sulfoxide functional group, and
      sulfoxide containing compound has so far never been reported in microorganisms.
      Biological assays revealed that xinghaiamine A exhibited broad-spectrum
      antibacterial activities to both Gram-negative persistent hospital pathogens
      (e.g. Acinetobacter baumannii, Pseudomonas aeruginosa and Escherichia coli) and
      Gram-positive ones, which include Staphylococcus aureus and Bacillus subtilis. In
      addition, xinghaiamine A also exhibited potent cytotoxic activity to human cancer
      cell lines of MCF-7 and U-937 with the IC50 of 0.6 and 0.5 uM, respectively. 

PMID- 24098414
TI  - Ligand pose and orientational sampling in molecular docking.
AB  - Molecular docking remains an important tool for structure-based screening to find
      new ligands and chemical probes. As docking ambitions grow to include new scoring
      function terms, and to address ever more targets, the reliability and
      extendability of the orientation sampling, and the throughput of the method,
      become pressing. Here we explore sampling techniques that eliminate stochastic
      behavior in DOCK3.6, allowing us to optimize the method for regularly variable
      sampling of orientations. This also enabled a focused effort to optimize the code
      for efficiency, with a three-fold increase in the speed of the program. This, in
      turn, facilitated extensive testing of the method on the 102 targets, 22,805
      ligands and 1,411,214 decoys of the Directory of Useful Decoys-Enhanced (DUD-E)
      benchmarking set, at multiple levels of sampling. Encouragingly, we observe that
      as sampling increases from 50 to 500 to 2000 to 5000 to 20,000 molecular
      orientations in the binding site (and so from about 1*10(10) to 4*10(10) to
      1*10(11) to 2*10(11) to 5*10(11) mean atoms scored per target, since multiple
      conformations are sampled per orientation), the enrichment of ligands over decoys
      monotonically increases for most DUD-E targets. Meanwhile, including internal
      electrostatics in the evaluation ligand conformational energies, and restricting
      aromatic hydroxyls to low energy rotamers, further improved enrichment values.
      Several of the strategies used here to improve the efficiency of the code are
      broadly applicable in the field.

PMID- 24098416
TI  - Phylogeography of the sponge Suberites diversicolor in Indonesia: insights into
      the evolution of marine lake populations.
AB  - The existence of multiple independently derived populations in landlocked marine
      lakes provides an opportunity for fundamental research into the role of isolation
      in population divergence and speciation in marine taxa. Marine lakes are
      landlocked water bodies that maintain a marine character through narrow submarine
      connections to the sea and could be regarded as the marine equivalents of
      terrestrial islands. The sponge Suberites diversicolor (Porifera: Demospongiae:
      Suberitidae) is typical of marine lake habitats in the Indo-Australian
      Archipelago. Four molecular markers (two mitochondrial and two nuclear) were
      employed to study genetic structure of populations within and between marine
      lakes in Indonesia and three coastal locations in Indonesia, Singapore and
      Australia. Within populations of S. diversicolor two strongly divergent lineages
      (A & B) (COI: p = 0.4% and ITS: p = 7.3%) were found, that may constitute cryptic
      species. Lineage A only occurred in Kakaban lake (East Kalimantan), while lineage
      B was present in all sampled populations. Within lineage B, we found low levels
      of genetic diversity in lakes, though there was spatial genetic population
      structuring. The Australian population is genetically differentiated from the
      Indonesian populations. Within Indonesia we did not record an East-West barrier,
      which has frequently been reported for other marine invertebrates. Kakaban lake
      is the largest and most isolated marine lake in Indonesia and contains the
      highest genetic diversity with genetic variants not observed elsewhere. Kakaban
      lake may be an area where multiple putative refugia populations have come into
      secondary contact, resulting in high levels of genetic diversity and a high
      number of endemic species. 

PMID- 24098417
TI  - Gender-specific metabolomic profiling of obesity in leptin-deficient ob/ob mice
      by 1H NMR spectroscopy.
AB  - Despite the numerous metabolic studies on obesity, gender bias in obesity has
      rarely been investigated. Here, we report the metabolomic analysis of obesity by
      using leptin-deficient ob/ob mice based on the gender. Metabolomic analyses of
      urine and serum from ob/ob mice compared with those from C57BL/6J lean mice,
      based on the (1)H NMR spectroscopy in combination with multivariate statistical
      analysis, revealed clear metabolic differences between obese and lean mice. We
      also identified 48 urine and 22 serum metabolites that were statistically
      significantly altered in obese mice compared to lean controls. These metabolites
      are involved in amino acid metabolism (leucine, alanine, ariginine, lysine, and
      methionine), tricarbocylic acid cycle and glucose metabolism (pyruvate, citrate,
      glycolate, acetoacetate, and acetone), lipid metabolism (cholesterol and
      carnitine), creatine metabolism (creatine and creatinine), and gut-microbiome
      derived metabolism (choline, TMAO, hippurate, p-cresol, isobutyrate, 2
      hydroxyisobutyrate, methylamine, and trigonelline). Notably, our metabolomic
      studies showed distinct gender variations. The obese male mice metabolism was
      specifically associated with insulin signaling, whereas the obese female mice
      metabolism was associated with lipid metabolism. Taken together, our study
      identifies the biomarker signature for obesity in ob/ob mice and provides
      biochemical insights into the metabolic alteration in obesity based on gender. 

PMID- 24098418
TI  - Prevalence of tobacco use in urban, semi urban and rural areas in and around
      Chennai City, India.
AB  - BACKGROUND: Tobacco use leads to many health complications and is a risk factor
      for the occurrence of cardio vascular diseases, lung and oral cancers, chronic
      bronchitis etc. Almost 6 million people die from tobacco-related causes every
      year. This study was conducted to measure the prevalence of tobacco use in three
      different areas around Chennai city, south India. METHODS: A survey of 7510
      individuals aged > = 15 years was undertaken covering Chennai city (urban),
      Ambattur (semi-urban) and Sriperumbudur (rural) taluk. Details on tobacco use
      were collected using a questionnaire adapted from both Global Youth Tobacco
      Survey and Global Adults Tobacco Survey. RESULTS: The overall prevalence of
      tobacco use was significantly higher in the rural (23.7%) compared to semi-urban
      (20.9%) and urban (19.4%) areas (P value <0.001) Tobacco smoking prevalence was
      14.3%, 13.9% and 12.4% in rural, semi-urban and urban areas respectively. The
      corresponding values for smokeless tobacco use were 9.5%, 7.0% and 7.0%
      respectively. Logistic regression analysis showed that the odds of using tobacco
      (with smoke or smokeless forms) was significantly higher among males, older
      individuals, alcoholics, in rural areas and slum localities. Behavioural pattern
      analysis of current tobacco users led to three groups (1) those who were not
      reached by family or friends to advice on harmful effects (2) those who were well
      aware of harmful effects of tobacco and even want to quit and (3) those are
      exposed to second hand/passive smoking at home and outside. CONCLUSIONS: Tobacco
      use prevalence was significantly higher in rural areas, slum dwellers, males and
      older age groups in this region of south India. Women used mainly smokeless
      tobacco. Tobacco control programmes need to develop strategies to address the
      different subgroups among tobacco users. Public health facilities need to expand
      smoking cessation counseling services as well as provide pharmacotherapy where
      necessary.

PMID- 24098419
TI  - Do baseline P-values follow a uniform distribution in randomised trials?
AB  - BACKGROUND: The theory has been put forward that if a null hypothesis is true, P
      values should follow a Uniform distribution. This can be used to check the
      validity of randomisation. METHOD: The theory was tested by simulation for two
      sample t tests for data from a Normal distribution and a Lognormal distribution,
      for two sample t tests which are not independent, and for chi-squared and
      Fisher's exact test using small and using large samples. RESULTS: For the two
      sample t test with Normal data the distribution of P-values was very close to the
      Uniform. When using Lognormal data this was no longer true, and the distribution
      had a pronounced mode. For correlated tests, even using data from a Normal
      distribution, the distribution of P-values varied from simulation run to
      simulation run, but did not look close to Uniform in any realisation. For binary
      data in a small sample, only a few probabilities were possible and distribution
      was very uneven. With a sample of two groups of 1,000 observations, there was
      great unevenness in the histogram and a poor fit to the Uniform. CONCLUSIONS: The
      notion that P-values for comparisons of groups using baseline data in randomised
      clinical trials should follow a Uniform distribution if the randomisation is
      valid has been found to be true only in the context of independent variables
      which follow a Normal distribution, not for Lognormal data, correlated variables,
      or binary data using either chi-squared or Fisher's exact tests. This should not
      be used as a check for valid randomisation.

PMID- 24098420
TI  - Changes in risk of immediate adverse reactions to iodinated contrast media by
      repeated administrations in patients with hepatocellular carcinoma.
AB  - BACKGROUND: To elucidate whether repeated exposures to iodinated contrast media
      increase the risk of adverse reaction. MATERIALS AND METHODS: We retrospectively
      reviewed 1,861 patients with hepatocellular carcinoma who visited authors'
      institution, a tertiary referral center, between 2004 and 2008. We analyzed
      cumulative probability of adverse reactions and risk factors. We categorized all
      symptoms into hypersensitivity reactions, physiologic reactions, and other
      reactions, according to the American College of Radiology guidelines, and
      evaluated each category as an event. We estimated the association between hazard
      for adverse reactions and the number of cumulative exposures to contrast media.
      We also evaluated subsequent contrast media injections and adverse reactions.
      RESULTS: There were 23,684 contrast media injections in 1,729 patients. One
      hundred and thirty-two patients were excluded because they were given no contrast
      media during the study period. Adverse reactions occurred in 196 (0.83%)
      patients. The cumulative incidence at 10(th), 20(th), and 30(th) examination was
      7.9%, 15.2%, and 24.1%, respectively. Presence of renal impairment was found to
      be one of risk factors for adverse reactions. The estimated hazard of overall
      adverse reaction gradually decreased until around 10(th) exposure and rose with
      subsequent exposures. The estimated hazard of hypersensitivity showed V-shaped
      change with cumulative number of exposures. The estimated hazard of physiologic
      reaction had a tendency toward decreasing and that of other reaction had a
      tendency toward increasing. Second adverse reaction was more severe than the
      initial in only one among 130 patients receiving subsequent injections.
      CONCLUSION: Repeated exposures to iodinated contrast media increase the risk of
      adverse reaction.

PMID- 24098422
TI  - Cumulative effect in information diffusion: empirical study on a microblogging
      network.
AB  - Cumulative effect in social contagion underlies many studies on the spread of
      innovation, behavior, and influence. However, few large-scale empirical studies
      are conducted to validate the existence of cumulative effect in information
      diffusion on social networks. In this paper, using the population-scale dataset
      from the largest Chinese microblogging website, we conduct a comprehensive study
      on the cumulative effect in information diffusion. We base our study on the
      diffusion network of message, where nodes are the involved users and links
      characterize forwarding relationship among them. We find that multiple exposures
      to the same message indeed increase the possibility of forwarding it. However,
      additional exposures cannot further improve the chance of forwarding when the
      number of exposures crosses its peak at two. This finding questions the
      cumulative effect hypothesis in information diffusion. Furthermore, to clarify
      the forwarding preference among users, we investigate both structural motif in
      the diffusion network and temporal pattern in information diffusion process.
      Findings provide some insights for understanding the variation of message
      popularity and explain the characteristics of diffusion network. 

PMID- 24098421
TI  - Soluble human leukocyte antigen-g5 activates extracellular signal-regulated
      protein kinase signaling and stimulates trophoblast invasion.
AB  - Soluble human leukocyte antigen-G (HLA-G) is a non-classical class Ib HLA
      molecule that is secreted from blastocysts. Soluble HLA-G modulates the immune
      tolerance of the mother and can be used as a prognostic factor for the clinical
      pregnancy rate. However, the underlying mechanism of how soluble HLA-G5 affects
      pregnancy remains largely unknown. We hypothesized that soluble HLA-G5 promotes
      successful implantation and pregnancy by modulating trophoblast invasion through
      receptor binding and activation of extracellular signal-regulated protein kinase
      (ERK) signaling pathway. Recombinant HLA-G5 protein over-expressed in E. coli
      BL21 was purified to near homogeneity. We studied the expression of HLA-G5 and
      its receptors, the leukocyte immunoglobulin-like receptor subfamily B1 (LILRB1)
      and killer cell immunoglobulin-like receptor 2DL4 (KIR2DL4), in primary
      trophoblasts and trophoblastic (JAr and JEG-3) cell lines by florescence-labeled
      HLA-G5. HLA-G5 was detected in the primary trophoblasts and JEG-3 cells. The
      LILRB1 and KIR2DL4 receptors were expressed in both primary trophoblasts and
      trophoblastic cell lines. HLA-G5 stimulated cell invasion (p<0.05) and increased
      urokinase (uPA) and matrix metalloproteinases (MMPs) transcripts and their
      activity (p<0.05) in trophoblastic cells. HLA-G5 activated the ERK signaling
      pathway and induced ERK1/2 phosphorylation in the trophoblastic cell lines.
      Addition of ERK inhibitors (U0126 and PD98059) nullified the stimulatory effect
      of HLA-G5 on trophoblastic cell invasion. Taken together, HLA-G5 induced
      trophoblast invasion by binding to KIR2DL4 and LILRB1, by increasing uPA and MMPs
      expressions and by activating the ERK signaling pathway. 

PMID- 24098423
TI  - Matrix matters: differences of grand skink metapopulation parameters in native
      tussock grasslands and exotic pasture grasslands.
AB  - Modelling metapopulation dynamics is a potentially very powerful tool for
      conservation biologists. In recent years, scientists have broadened the range of
      variables incorporated into metapopulation modelling from using almost
      exclusively habitat patch size and isolation, to the inclusion of attributes of
      the matrix and habitat patch quality. We investigated the influence of habitat
      patch and matrix characteristics on the metapopulation parameters of a highly
      endangered lizard species, the New Zealand endemic grand skink (Oligosoma grande)
      taking into account incomplete detectability. The predictive ability of the
      developed zxmetapopulation model was assessed through cross-validation of the
      data and with an independent data-set. Grand skinks occur on scattered rock
      outcrops surrounded by indigenous tussock (bunch) and pasture grasslands
      therefore implying a metapopulation structure. We found that the type of matrix
      surrounding the habitat patch was equally as important as the size of habitat
      patch for estimating occupancy, colonisation and extinction probabilities.
      Additionally, the type of matrix was more important than the physical distance
      between habitat patches for colonisation probabilities. Detection probability
      differed between habitat patches in the two matrix types and between habitat
      patches with different attributes such as habitat patch composition and abundance
      of vegetation on the outcrop. The developed metapopulation models can now be used
      for management decisions on area protection, monitoring, and the selection of
      translocation sites for the grand skink. Our study showed that it is important to
      incorporate not only habitat patch size and distance between habitat patches, but
      also those matrix type and habitat patch attributes which are vital in the
      ecology of the target species. 

PMID- 24098424
TI  - Metagenomic profiling of antibiotic resistance genes and mobile genetic elements
      in a tannery wastewater treatment plant.
AB  - Antibiotics are often used to prevent sickness and improve production in animal
      agriculture, and the residues in animal bodies may enter tannery wastewater
      during leather production. This study aimed to use Illumina high-throughput
      sequencing to investigate the occurrence, diversity and abundance of antibiotic
      resistance genes (ARGs) and mobile genetic elements (MGEs) in aerobic and
      anaerobic sludge of a full-scale tannery wastewater treatment plant (WWTP).
      Metagenomic analysis showed that Proteobacteria, Firmicutes, Bacteroidetes and
      Actinobacteria dominated in the WWTP, but the relative abundance of archaea in
      anaerobic sludge was higher than in aerobic sludge. Sequencing reads from aerobic
      and anaerobic sludge revealed differences in the abundance of functional genes
      between both microbial communities. Genes coding for antibiotic resistance were
      identified in both communities. BLAST analysis against Antibiotic Resistance
      Genes Database (ARDB) further revealed that aerobic and anaerobic sludge
      contained various ARGs with high abundance, among which sulfonamide resistance
      gene sul1 had the highest abundance, occupying over 20% of the total ARGs reads.
      Tetracycline resistance genes (tet) were highly rich in the anaerobic sludge,
      among which tet33 had the highest abundance, but was absent in aerobic sludge.
      Over 70 types of insertion sequences were detected in each sludge sample, and
      class 1 integrase genes were prevalent in the WWTP. The results highlighted
      prevalence of ARGs and MGEs in tannery WWTPs, which may deserve more public
      health concerns. 

PMID- 24098425
TI  - Risk factors associated with sleep disturbance following traumatic brain injury:
      clinical findings and questionnaire based study.
AB  - BACKGROUND: Sleep disturbance is very common following traumatic brain injury
      (TBI), which may initiate or exacerbate a variety of co-morbidities and
      negatively impact rehabilitative treatments. To date, there are paradoxical
      reports regarding the associations between inherent characteristics of TBI and
      sleep disturbance in TBI population. The current study was designed to explore
      the relationship between the presence of sleep disturbance and characteristics of
      TBI and identify the factors which are closely related to the presence of sleep
      disturbance in TBI population. METHODS: 98 TBI patients (72 males, mean age +/-
      SD, 47 +/- 13 years, range 18-70) were recruited. Severity of TBI was evaluated
      based on Glasgow Coma Scale (GCS). All participants performed cranial computed
      tomography and were examined on self-reported sleep quality, anxiety, and
      depression. RESULTS: TBI was mild in 69 (70%), moderate in 15 (15%) and severe in
      14 (15%) patients. 37 of 98 patients (38%) reported sleep disturbance following
      TBI. Insomnia was diagnosed in 28 patients (29%) and post-traumatic hypersomnia
      in 9 patients (9%). In TBI with insomnia group, 5 patients (18%) complained of
      difficulty falling asleep only, 8 patients (29%) had difficulty maintaining sleep
      without difficulty in initial sleep and 15 patients (53%) presented both
      difficulty falling asleep and difficulty maintaining sleep. Risk factors
      associated with insomnia were headache and/or dizziness and more symptoms of
      anxiety and depression rather than GCS. In contrast, GCS was independently
      associated with the presence of hypersomnia following TBI. Furthermore, there was
      no evidence of an association between locations of brain injury and the presence
      of sleep disturbance after TBI. CONCLUSION: Our data support and contribute to a
      growing body of evidence which indicates that TBI patients with insomnia are
      prone to suffer from concomitant headache and/or dizziness, report more symptoms
      of anxiety and depression and severe TBI patients are likely to experience
      hypersomnia.

PMID- 24098426
TI  - Preferential lentiviral targeting of astrocytes in the central nervous system.
AB  - The ability to visualize and genetically manipulate specific cell populations of
      the central nervous system (CNS) is fundamental to a better understanding of
      brain functions at the cellular and molecular levels. Tools to selectively target
      cells of the CNS include molecular genetics, imaging, and use of transgenic
      animals. However, these approaches are technically challenging, time consuming,
      and difficult to control. Viral-mediated targeting of cells in the CNS can be
      highly beneficial for studying and treating neurodegenerative diseases. Yet,
      despite specific marking of numerous cell types in the CNS, in vivo selective
      targeting of astrocytes has not been optimized. In this study, preferential
      targeting of astrocytes in the CNS was demonstrated using engineered lentiviruses
      that were pseudotyped with a modified Sindbis envelope and displayed anti-GLAST
      IgG on their surfaces as an attachment moiety. Viral tropism for astrocytes was
      initially verified in vitro in primary mixed glia cultures. When injected into
      the brains of mice, lentiviruses that displayed GLAST IgG on their surface,
      exhibited preferential astrocyte targeting, compared to pseudotyped lentiviruses
      that did not incorporate any IgG or that expressed a control isotype IgG.
      Overall, this approach is highly flexible and can be exploited to selectively
      target astrocytes or other cell types of the CNS. As such, it can open a window
      to visualize and genetically manipulate astrocytes or other cells of the CNS as
      means of research and treatment. 

PMID- 24098427
TI  - Transgenic mosquitoes expressing a phospholipase A(2) gene have a fitness
      advantage when fed Plasmodium falciparum-infected blood.
AB  - BACKGROUND: Genetically modified mosquitoes have been proposed as an alternative
      strategy to reduce the heavy burden of malaria. In recent years, several proof-of
      principle experiments have been performed that validate the idea that mosquitoes
      can be genetically modified to become refractory to malaria parasite development.
      RESULTS: We have created two transgenic lines of Anophelesstephensi, a natural
      vector of Plasmodium falciparum, which constitutively secrete a catalytically
      inactive phospholipase A2 (mPLA2) into the midgut lumen to interfere with
      Plasmodium ookinete invasion. Our experiments show that both transgenic lines
      expressing mPLA2 significantly impair the development of rodent malaria
      parasites, but only one line impairs the development of human malaria parasites.
      In addition, when fed on malaria-infected blood, mosquitoes from both transgenic
      lines are more fecund than non-transgenic mosquitoes. Consistent with these
      observations, cage experiments with mixed populations of transgenic and non
      transgenic mosquitoes show that the percentage of transgenic mosquitoes increases
      when maintained on Plasmodium-infected blood. CONCLUSIONS: Our results suggest
      that the expression of an anti-Plasmodium effector gene gives transgenic
      mosquitoes a fitness advantage when fed malaria-infected blood. These findings
      have important implications for future applications of transgenic mosquito
      technology in malaria control.

PMID- 24098428
TI  - The graft of autologous adipose-derived stem cells in the corneal stromal after
      mechanic damage.
AB  - This study was designed to explore the feasibility of using autologous rabbit
      adipose derived stem cells (rASCs) as seed cells and polylactic-co-glycolic acid
      (PLGA) as a scaffold for repairing corneal stromal defects. rASCs isolated from
      rabbit nape adipose tissue were expanded and seeded on a PLGA scaffold to
      fabricate cell-scaffold constructs. After 1 week of cultivation in vitro, the
      cell-scaffold complexes were transplanted into corneal stromal defects in
      rabbits. In vivo, the autologous rASCs-PLGA constructed corneal stroma gradually
      became transparent without corneal neovascularization after 12 weeks. Hematoxylin
      and eosin staining and transmission electron microscopy examination revealed that
      their histological structure and collagen fibril distribution at 24 weeks after
      implantation were similar to native counterparts. As to the defect treated with
      PLGA alone, the stromal defects remained. And scar tissue was observed in the
      untreated-group. The implanted autologous ASCs survived up to 24 weeks post
      transplantation and differentiated into functional keratocytes, as assessed by
      the expression of aldehyde-3-dehydrogenase1A1 (ALDH1A1) and cornea-specific
      proteoglycan keratocan. Our results revealed that autologous rASCs could be one
      of the cell sources for corneal stromal restoration in diseased corneas or for
      tissue engineering of a corneal equivalent. 

PMID- 24098429
TI  - Human papillomavirus prevalence in a population of women living in Port-au-Prince
      and Leogane, Haiti.
AB  - BACKGROUND: There have been no published studies of carcinogenic human
      papillomavirus (HPV)--the necessary cause of cervical cancer--in Haiti, a nation
      that has one of the greatest burdens of cervical cancer globally. OBJECTIVE:
      Characterize prevalence of carcinogenic HPV and the prevalence of individual
      carcinogenic HPV genotypes in women with cervical precancer or cancer, cervical
      intraepithelial neoplasia grade 2 (CIN2) or more severe (CIN2+). METHODS: Women
      (n=9,769; aged 25-60 years) were screened for carcinogenic HPV by Hybrid Capture
      2 (HC2; Qiagen, Gaithersburg, MD). Carcinogenic HPV positives underwent
      colposcopy and visible lesions were biopsied. A subset of carcinogenic HPV
      positives was tested for individual HPV genotypes using a GP5+/6+ assay. RESULTS:
      The prevalence of carcinogenic HPV was 19.0% (95% confidence interval: 18.4%
      19.9%) and decreased with increasing age (ptrend < 0.001). Women with 3 or more
      sexual partners and who started sex before the age of 18 years had twice the age
      adjusted prevalence of carcinogenic HPV of women with one partner and who started
      sex after the age of 21 (24.3% vs. 12.9%, respectively). HPV16 and HPV35 were the
      most common HPV genotypes detected in CIN2+ and more common in women with CIN2+
      than those without CIN2+. HPV16 and/or HPV18 were detected in 21.0% of CIN2 (n =
      42), 46.2% of CIN3 (n = 52), and 80% of cancers (n = 5). CONCLUSIONS: The
      prevalence of carcinogenic HPV in Haiti was much greater than the prevalence in
      other Latin American countries. High carcinogenic HPV prevalence and a lack of
      cervical cancer screening may explain the high burden of cervical cancer in
      Haiti.

PMID- 24098430
TI  - How changes in extracellular matrix mechanics and gene expression variability
      might combine to drive cancer progression.
AB  - Changes in extracellular matrix (ECM) structure or mechanics can actively drive
      cancer progression; however, the underlying mechanism remains unknown. Here we
      explore whether this process could be mediated by changes in cell shape that lead
      to increases in genetic noise, given that both factors have been independently
      shown to alter gene expression and induce cell fate switching. We do this using a
      computer simulation model that explores the impact of physical changes in the
      tissue microenvironment under conditions in which physical deformation of cells
      increases gene expression variability among genetically identical cells. The
      model reveals that cancerous tissue growth can be driven by physical changes in
      the microenvironment: when increases in cell shape variability due to growth
      dependent increases in cell packing density enhance gene expression variation,
      heterogeneous autonomous growth and further structural disorganization can
      result, thereby driving cancer progression via positive feedback. The model
      parameters that led to this prediction are consistent with experimental
      measurements of mammary tissues that spontaneously undergo cancer progression in
      transgenic C3(1)-SV40Tag female mice, which exhibit enhanced stiffness of mammary
      ducts, as well as progressive increases in variability of cell-cell relations and
      associated cell shape changes. These results demonstrate the potential for
      physical changes in the tissue microenvironment (e.g., altered ECM mechanics) to
      induce a cancerous phenotype or accelerate cancer progression in a clonal
      population through local changes in cell geometry and increased phenotypic
      variability, even in the absence of gene mutation. 

PMID- 24098431
TI  - Intraoperative blood loss independently predicts survival and recurrence after
      resection of colorectal cancer liver metastasis.
AB  - BACKGROUND: Although numerous prognostic factors have been reported for
      colorectal cancer liver metastasis (CRLM), few studies have reported
      intraoperative blood loss (IBL) effects on clinical outcome after CRLM resection.
      METHODS: We retrospectively evaluated the clinical and histopathological
      characteristics of 139 patients who underwent liver resection for CRLM. The IBL
      cutoff volume was calculated using receiver operating characteristic curves.
      Overall survival (OS) and recurrence free survival (RFS) were assessed using the
      Kaplan-Meier and Cox regression methods. RESULTS: All patients underwent curative
      resection. The median follow up period was 25.0 months (range, 2.1-88.8). Body
      mass index (BMI) and CRLM number and tumor size were associated with increased
      IBL. BMI (P=0.01; 95% CI = 1.3-8.5) and IBL (P<0.01; 95% CI = 1.6-12.5) were
      independent OSOs predictors. Five factors, including IBL (P=0.02; 95% CI = 1.1
      4.1), were significantly related to RFS via multivariate Cox regression analysis.
      In addition, OSOs and RFS significantly decreased with increasing IBL volumes.
      The 5-year OSOs of patients with IBL<=250, 250-500, and >500mL were 71%, 33%, and
      0%, respectively (P<0.01). RFS of patients within three IBL volumes at the end of
      the first year were 67%, 38%, and 18%, respectively (P<0.01). CONCLUSIONS: IBL
      during CRLM resection is an independent predictor of long term survival and tumor
      recurrence, and its prognostic value was confirmed by a dose-response
      relationship.

PMID- 24098432
TI  - Expression patterns of the Drosophila neuropeptide CCHamide-2 and its receptor
      may suggest hormonal signaling from the gut to the brain.
AB  - The insect neuropeptides CCHamide-1 and -2 are recently discovered peptides that
      probably occur in all arthropods. Here, we used immunocytochemistry, in situ
      hybridization, and quantitative PCR (qPCR), to localize the two peptides in the
      fruitfly Drosophila melanogaster. We found that CCHamide-1 and -2 were localized
      in endocrine cells of the midgut of larvae and adult flies. These endocrine cells
      had the appearance of sensory cells, projecting processes close to or into the
      gut lumen. In addition, CCHamide-2 was also localized in about forty neurons in
      the brain hemispheres and ventral nerve cord of larvae. Using qPCR we found high
      expression of the CCHamide-2 gene in the larval gut and very low expression of
      its receptor gene, while in the larval brain we found low expression of CCHamide
      2 and very high expression of its receptor. These expression patterns suggest the
      following model: Endocrine CCHamide-2 cells in the gut sense the quality of food
      components in the gut lumen and transmit this information to the brain by
      releasing CCHamide-2 into the circulation; subsequently, after binding to its
      brain receptors, CCHamides-2 induces an altered feeding behavior in the animal
      and possibly other homeostatic adaptations. 

PMID- 24098433
TI  - Improved production of 2,3-butanediol in Bacillus amyloliquefaciens by over
      expression of glyceraldehyde-3-phosphate dehydrogenase and 2,3-butanediol
      dehydrogenase.
AB  - BACKGROUND: Previously, a safe strain, Bacillus amyloliquefaciens B10-127 was
      identified as an excellent candidate for industrial-scale microbial fermentation
      of 2,3-butanediol (2,3-BD). However, B. amyloliquefaciens fermentation yields
      large quantities of acetoin, lactate and succinate as by-products, and the 2,3-BD
      yield remains prohibitively low for commercial production. METHODOLOGY/PRINCIPAL
      FINDINGS: In the 2,3-butanediol metabolic pathway, glyceraldehyde-3-phosphate
      dehydrogenase (GAPDH) catalyzes the conversion of 3-phosphate glyceraldehyde to
      1,3-bisphosphoglycerate, with concomitant reduction of NAD(+) to NADH. In the
      same pathway, 2,3-BD dehydrogenase (BDH) catalyzes the conversion of acetoin to
      2,3-BD with concomitant oxidation of NADH to NAD(+). In this study, to improve
      2,3-BD production, we first over-produced NAD(+)-dependent GAPDH and NADH
      dependent BDH in B. amyloliquefaciens. Excess GAPDH reduced the fermentation
      time, increased the 2,3-BD yield by 12.7%, and decreased the acetoin titer by
      44.3%. However, the process also enhanced lactate and succinate production.
      Excess BDH increased the 2,3-BD yield by 16.6% while decreasing acetoin, lactate
      and succinate production, but prolonged the fermentation time. When BDH and GAPDH
      were co-overproduced in B. amyloliquefaciens, the fermentation time was reduced.
      Furthermore, in the NADH-dependent pathways, the molar yield of 2,3-BD was
      increased by 22.7%, while those of acetoin, lactate and succinate were reduced by
      80.8%, 33.3% and 39.5%, relative to the parent strain. In fed-batch
      fermentations, the 2,3-BD concentration was maximized at 132.9 g/l after 45 h,
      with a productivity of 2.95 g/l.h. CONCLUSIONS/SIGNIFICANCE: Co-overexpression of
      bdh and gapA genes proved an effective method for enhancing 2,3-BD production and
      inhibiting the accumulation of unwanted by-products (acetoin, lactate and
      succinate). To our knowledge, we have attained the highest 2,3-BD fermentation
      yield thus far reported for safe microorganisms.

PMID- 24098435
TI  - Management intensity and topography determined plant diversity in vineyards.
AB  - Vineyards are amongst the most intensive forms of agriculture often resulting in
      simplified landscapes where semi-natural vegetation is restricted to small
      scattered patches. However, a tendency toward a more sustainable management is
      stimulating research on biodiversity in these poorly investigated agro
      ecosystems. The main aim of this study was to test the effect on plant diversity
      of management intensity and topography in vineyards located in a homogenous
      intensive hilly landscape. Specifically, this study evaluated the role of slope,
      mowing and herbicide treatments frequency, and nitrogen supply in shaping plant
      diversity and composition of life-history traits. The study was carried out in 25
      vineyards located in the area of the Conegliano-Valdobbiadene DOCG (Veneto, NE
      Italy). In each vineyard, 10 plots were placed and the abundance of all vascular
      plants was recorded in each plot. Linear multiple regression was used to test the
      effect of management and topography on plant diversity. Management intensity and
      topography were both relevant drivers of plant species diversity patterns in our
      vineyards. The two most important factors were slope and mowing frequency that
      respectively yielded positive and negative effects on plant diversity. A
      significant interaction between these two factors was also demonstrated, warning
      against the detrimental effects of increasing mowing intensity on steep slope
      where plant communities are more diverse. The response of plant communities to
      mowing frequency is mediated by a process of selection of resistant growth forms,
      such in the case of rosulate and reptant species. The other two management
      related factors tested in this study, number of herbicide treatments and N
      fertilization, were less influential. In general, our study corroborates the idea
      that some simple changes in farming activities, which are compatible with grape
      production, should be encouraged for improving the natural and cultural value of
      the landscape by maintaining and improving wild plant diversity. 

PMID- 24098437
TI  - Differential binding of IgG and IgA to mucus of the female reproductive tract.
AB  - Cells of the endocervix are responsible for the secretion of mucins, which
      provide an additional layer of protection to the female reproductive tract (FRT).
      This barrier is likely fortified with IgA as has previously been shown in the
      gastrointestinal tract and lungs of mice. Mucus associated IgA can facilitate
      clearance of bacteria. While a similar function for IgG has been proposed, an
      association with mucus has not yet been demonstrated. Here we find that IgA and
      IgG are differentially associated with the different types of mucus of the FRT.
      We observed that while both IgA and IgG are stably associated with cervical
      mucus, only IgG is associated with cervicovaginal mucus. These findings reveal
      that antibodies can bind tightly to mucus, where they can play a significant role
      in the fortification of the mucus barriers of the FRT. It may be possible to
      harness this interaction in the development of vaccines designed to protect the
      FRT mucosal barriers from sexually transmitted diseases such as HIV. 

PMID- 24098436
TI  - The phylogeographic history of the new world screwworm fly, inferred by
      approximate bayesian computation analysis.
AB  - Insect pest phylogeography might be shaped both by biogeographic events and by
      human influence. Here, we conducted an approximate Bayesian computation (ABC)
      analysis to investigate the phylogeography of the New World screwworm fly,
      Cochliomyia hominivorax, with the aim of understanding its population history and
      its order and time of divergence. Our ABC analysis supports that populations
      spread from North to South in the Americas, in at least two different moments.
      The first split occurred between the North/Central American and South American
      populations in the end of the Last Glacial Maximum (15,300-19,000 YBP). The
      second split occurred between the North and South Amazonian populations in the
      transition between the Pleistocene and the Holocene eras (9,100-11,000 YBP). The
      species also experienced population expansion. Phylogenetic analysis likewise
      suggests this north to south colonization and Maxent models suggest an increase
      in the number of suitable areas in South America from the past to present. We
      found that the phylogeographic patterns observed in C. hominivorax cannot be
      explained only by climatic oscillations and can be connected to host population
      histories. Interestingly we found these patterns are very coincident with general
      patterns of ancient human movements in the Americas, suggesting that humans might
      have played a crucial role in shaping the distribution and population structure
      of this insect pest. This work presents the first hypothesis test regarding the
      processes that shaped the current phylogeographic structure of C. hominivorax and
      represents an alternate perspective on investigating the problem of insect pests.

PMID- 24098434
TI  - Clinical differences between younger and older adults with HIV/AIDS starting
      antiretroviral therapy in Uganda and Zimbabwe: a secondary analysis of the DART
      trial.
AB  - OBJECTIVE: Clinical and immunological data about HIV in older adults from low and
      middle income countries is scarce. We aimed to describe differences between
      younger and older adults with HIV starting antiretroviral therapy in two low
      income African countries. METHODS:  SETTING: HIV clinics in Uganda and Zimbabwe.
      DESIGN: Secondary exploratory cross-sectional analysis of the DART randomized
      controlled trial. OUTCOME MEASURES: Clinical and laboratory characteristics were
      compared between adults aged 18-49 years (younger) and >= 50 years (older), using
      two exploratory multivariable logistic regression models, one with HIV viral load
      (measured in a subset pre-ART) and one without. RESULTS: A total of 3316 eligible
      participants enrolled in DART were available for analysis; 219 (7%) were >= 50
      years and 1160 (35%) were male. Across the two adjusted regression models, older
      adults had significantly higher systolic blood pressure, lower creatinine
      clearance and were consistently less likely to be females compared to younger
      adults with HIV. Paradoxically, the models separately suggested that older adults
      had statistically significant (but not clinically important) higher CD4+ cell
      counts and higher plasma HIV-1 viral copies at initiation. Crude associations
      between older age and higher baseline hemoglobin, body mass index, diastolic
      blood pressure and lower WHO clinical stage were not sustained in the adjusted
      analysis. CONCLUSIONS: Our study found clinical and immunological differences
      between younger and older adults, in a cohort of Africans starting antiretroviral
      therapy. Further investigations should explore how these differences could be
      used to ensure equity in service delivery and affect outcomes of antiretroviral
      therapy.

PMID- 24098438
TI  - TCam-2 seminoma cells exposed to egg-derived microenvironment modify their shape,
      adhesive pattern and migratory behaviour: a molecular and morphometric analysis.
AB  - Seminoma is one of the most common Testicular Germ Cell Tumours that originates
      during embryonic development due to an alteration of the local niche that in turn
      results in a delayed or blocked differentiation of Primordial Germ Cells. The
      block of differentiation is actually a common way to develop cancer disease as
      postulated by the "embryonic rest theory of cancer". In agreement with this
      theory different studies have demonstrated that embryonic cues display the
      capacity of reprogramming aggressive cancer cells towards a less aggressive
      phenotype. Herein we investigate the ability of a culture medium added with 10%
      egg albumen (EW, Egg White) to modulate seminoma cell phenotype and behaviour, by
      ensuring a proper set of morphogenetic signals. We chose to use the TCam-2
      seminoma cell line that has been established as the only available cell line,
      obtained from a primary testicular seminoma. EW is able to: 1) modify TCam-2 cell
      spreading rate and cell-substrate adhesion without affecting proliferation and
      survival indexes; 2) modulate TCam-2 actin distribution pattern increasing
      cortical localization of actin filaments; 3) increase TCam-2 cell-cell junction
      capability; 4) decrease both chemo-sensitive and collective TCam-2 migratory
      behaviour. According to these observations morphometric fractal analysis revealed
      the ability of EW to increase Circularity and Solidity parameters and,
      consequently, to decrease Fractal dimension. Prompted by these observations we
      hypothesize that EW treatment could rescue, at least in part, the neoplastic
      metastatic behaviour of seminoma cells. 

PMID- 24098439
TI  - Extraneuronal monoamine transporter mediates the permissive action of cortisol in
      the Guinea pig trachea: possible involvement of tracheal chondrocytes.
AB  - Cortisol, a member of glucocorticoids, could potentiate the action of
      catecholamine by a non-genomic mechanism. Although this permissive effect has
      been well appreciated in the anti-asthmatic medication, the underlying signaling
      pathway has remained mysterious. Here, we show that extraneuronal monoamine
      transporter (EMT), a membraneous reuptake transporter for circulating
      catecholamine clearance, is the direct target of cortisol in its permissive
      effect. We found that BSA-conjugated cortisol, which functions as a cortisol but
      cannot penetrate cell membrane, enhanced the spasmolytic effect of beta
      adrenoceptor agonist (isoprenaline) in histamine-sensitized tracheal spirals of
      guinea pigs, and pharmacological inhibition of EMT with famotidine was powerful
      enough to imitate the permissive action of cortisol. To our surprise, EMT protein
      expression was high in the chondrocytes of tracheal cartilage, but was
      undetectable in tracheal smooth muscle cells. The functionality of EMT was
      further confirmed with measurement of catecholamine uptake by tracheal
      chondrocytes. Moreover, cortisol-initiated membrane signaling could activate
      protein kinase C (PKC), which phosphorylates EMT and induces its internalization
      via a lipid raft-dependent pathway. Both of the mechanisms slow down the reuptake
      process by chondrocytes, leading to extracellular catecholamine accumulation and
      results in a more profound adrenergic signaling activation in tracheal smooth
      muscle cells. Thus, an EMT-centered pathway was proposed to explain the
      permissive action of cortisol. Collectively, our results highlight the role of
      EMT in the crosstalk between glucocorticoid and catecholamine. EMT may represent
      a promising target for adrenergic signaling modulation. 

PMID- 24098440
TI  - Subcellular RNA sequencing reveals broad presence of cytoplasmic intron-sequence
      retaining transcripts in mouse and rat neurons.
AB  - Recent findings have revealed the complexity of the transcriptional landscape in
      mammalian cells. One recently described class of novel transcripts are the
      Cytoplasmic Intron-sequence Retaining Transcripts (CIRTs), hypothesized to confer
      post-transcriptional regulatory function. For instance, the neuronal CIRT
      KCNMA1i16 contributes to the firing properties of hippocampal neurons. Intronic
      sub-sequence retention within IL1-beta mRNA in anucleate platelets has been
      implicated in activity-dependent splicing and translation. In a recent study, we
      showed CIRTs harbor functional SINE ID elements which are hypothesized to mediate
      dendritic localization in neurons. Based on these studies and others, we
      hypothesized that CIRTs may be present in a broad set of transcripts and comprise
      novel signals for post-transcriptional regulation. We carried out a transcriptome
      wide survey of CIRTs by sequencing micro-dissected subcellular RNA fractions. We
      sequenced two batches of 150-300 individually dissected dendrites from primary
      cultures of hippocampal neurons in rat and three batches from mouse hippocampal
      neurons. After statistical processing to minimize artifacts, we found a broad
      prevalence of CIRTs in the neurons in both species (44-60% of the expressed
      transcripts). The sequence patterns, including stereotypical length, biased
      inclusion of specific introns, and intron-intron junctions, suggested CIRT
      specific nuclear processing. Our analysis also suggested that these cytoplasmic
      intron-sequence retaining transcripts may serve as a primary transcript for
      ncRNAs. Our results show that retaining intronic sequences is not isolated to a
      few loci but may be a genome-wide phenomenon for embedding functional signals
      within certain mRNA. The results hypothesize a novel source of cis-sequences for
      post-transcriptional regulation. Our results hypothesize two potentially novel
      splicing pathways: one, within the nucleus for CIRT biogenesis; and another,
      within the cytoplasm for removing CIRT sequences before translation. We also
      speculate that release of CIRT sequences prior to translation may form RNA-based
      signals within the cell potentially comprising a novel class of signaling
      pathways. 

PMID- 24098441
TI  - Pseudomonas putida AlkA and AlkB proteins comprise different defense systems for
      the repair of alkylation damage to DNA - in vivo, in vitro, and in silico
      studies.
AB  - Alkylating agents introduce cytotoxic and/or mutagenic lesions to DNA bases
      leading to induction of adaptive (Ada) response, a mechanism protecting cells
      against deleterious effects of environmental chemicals. In Escherichia coli, the
      Ada response involves expression of four genes: ada, alkA, alkB, and aidB. In
      Pseudomonas putida, the organization of Ada regulon is different, raising
      questions regarding regulation of Ada gene expression. The aim of the presented
      studies was to analyze the role of AlkA glycosylase and AlkB dioxygenase in
      protecting P. putida cells against damage to DNA caused by alkylating agents. The
      results of bioinformatic analysis, of survival and mutagenesis of methyl
      methanesulfonate (MMS) or N-methyl-N'-nitro-N-nitrosoguanidine (MNNG) treated P.
      putida mutants in ada, alkA and alkB genes as well as assay of promoter activity
      revealed diverse roles of Ada, AlkA and AlkB proteins in protecting cellular DNA
      against alkylating agents. We found AlkA protein crucial to abolish the cytotoxic
      but not the mutagenic effects of alkylans since: (i) the mutation in the alkA
      gene was the most deleterious for MMS/MNNG treated P. putida cells, (ii) the
      activity of the alkA promoter was Ada-dependent and the highest among the tested
      genes. P. putida AlkB (PpAlkB), characterized by optimal conditions for in vitro
      repair of specific substrates, complementation assay, and M13/MS2 survival test,
      allowed to establish conservation of enzymatic function of P. putida and E. coli
      AlkB protein. We found that the organization of P. putida Ada regulon differs
      from that of E. coli. AlkA protein induced within the Ada response is crucial for
      protecting P. putida against cytotoxicity, whereas Ada prevents the mutagenic
      action of alkylating agents. In contrast to E. coli AlkB (EcAlkB), PpAlkB remains
      beyond the Ada regulon and is expressed constitutively. It probably creates a
      backup system that protects P. putida strains defective in other DNA repair
      systems against alkylating agents of exo- and endogenous origin. 

PMID- 24098442
TI  - A novel role for adipose ephrin-B1 in inflammatory response.
AB  - AIMS: Ephrin-B1 (EfnB1) was selected among genes of unknown function in
      adipocytes or adipose tissue and subjected to thorough analysis to understand its
      role in the development of obesity. METHODS AND RESULTS: EfnB1 mRNA and protein
      levels were significantly decreased in adipose tissues of obese mice and such
      reduction was mainly observed in mature adipocytes. Exposure of 3T3-L1 adipocytes
      to tumor necrosis factor-alpha (TNF-alpha) and their culture with RAW264.7 cells
      reduced EFNB1 levels. Knockdown of adipose EFNB1 increased monocyte
      chemoattractant protein-1 (Mcp-1) mRNA level and augmented the TNF-alpha-mediated
      THP-1 monocyte adhesion to adipocytes. Adenovirus-mediated adipose EFNB1
      overexpression significantly reduced the increase in Mcp-1 mRNA level induced by
      coculture of 3T3-L1 adipocytes with RAW264.7 cells. Monocyte adherent assay
      showed that adipose EfnB1-overexpression significantly decreased the increase of
      monocyte adhesion by coculture with RAW264.7 cells. TNF-alpha-induced activation
      of extracellular signal-regulated kinase 1/2 (ERK1/2) was reduced by EFNB1
      overexpression. CONCLUSIONS: EFNB1 contributes to the suppression of adipose
      inflammatory response. In obesity, reduction of adipose EFNB1 may accelerate the
      vicious cycle involved in adipose tissue inflammation.

PMID- 24098443
TI  - Regulation of dendritic filopodial interactions by ZO-1 and implications for
      dendrite morphogenesis.
AB  - Neuronal dendrites dynamically protrude many fine filopodia in the early stages
      of neuronal development and gradually establish complex structures. The
      importance of the dendritic filopodia in the formation of axo-dendritic
      connections is established, but their role in dendrite morphogenesis remains
      unknown. Using time-lapse imaging of cultured rat hippocampal neurons, we
      revealed here that many filopodia dynamically protruded from dendrites and
      transiently interacted with each other to form dendritic filopodia-filopodia
      contacts in the early stages of neuronal development. The MAGUK family member,
      Zonula Occludens-1 (ZO-1), which is known to be associated with the nectin and
      cadherin cell adhesion systems, was concentrated at these dendritic filopodia
      filopodia contact sites and also at the tips of free dendritic filopodia.
      Overexpression of ZO-1 increased the formation of dendritic filopodia and their
      interactions, and induced abnormal dendrite morphology. Conversely, knockdown of
      ZO-1 decreased the formation of dendritic filopodia and their interactions, and
      induced abnormal dendrite morphology which was different from that induced by the
      overexpression of ZO-1. The components of the nectin and cadherin systems were co
      localized with ZO-1 at the dendritic filopodia-filopodia contact sites, but not
      at the tips of free dendritic filopodia. Overexpression of ZO-1 increased the
      accumulation of these cell adhesive components at the dendritic filopodia
      filopodia contact sites and stabilized their interactions, whereas knockdown of
      ZO-1 reduced their accumulation at the dendritic filopodia-filopodia contact
      sites. These results indicate that ZO-1 regulates dendritic filopodial dynamics,
      which is implicated in dendrite morphogenesis cooperatively with the nectin and
      cadherin systems in cultured neurons. 

PMID- 24098444
TI  - A novel feeder-free culture system for human pluripotent stem cell culture and
      induced pluripotent stem cell derivation.
AB  - Correct interactions with extracellular matrix are essential to human pluripotent
      stem cells (hPSC) to maintain their pluripotent self-renewal capacity during in
      vitro culture. hPSCs secrete laminin 511/521, one of the most important
      functional basement membrane components, and they can be maintained on human
      laminin 511 and 521 in defined culture conditions. However, large-scale
      production of purified or recombinant laminin 511 and 521 is difficult and
      expensive. Here we have tested whether a commonly available human choriocarcinoma
      cell line, JAR, which produces high quantities of laminins, supports the growth
      of undifferentiated hPSCs. We were able to maintain several human pluripotent
      stem cell lines on decellularized matrix produced by JAR cells using a defined
      culture medium. The JAR matrix also supported targeted differentiation of the
      cells into neuronal and hepatic directions. Importantly, we were able to derive
      new human induced pluripotent stem cell (hiPSC) lines on JAR matrix and show that
      adhesion of the early hiPSC colonies to JAR matrix is more efficient than to
      matrigel. In summary, JAR matrix provides a cost-effective and easy-to-prepare
      alternative for human pluripotent stem cell culture and differentiation. In
      addition, this matrix is ideal for the efficient generation of new hiPSC lines. 

PMID- 24098445
TI  - Pro-inflammatory action of MIF in acute myocardial infarction via activation of
      peripheral blood mononuclear cells.
AB  - OBJECTIVES: Macrophage migration inhibitory factor (MIF), a pro-inflammatory
      cytokine, has been implicated in the pathogenesis of multiple inflammatory
      disorders. We determined changes in circulating MIF levels, explored the cellular
      source of MIF, and studied the role of MIF in mediating inflammatory responses
      following acute myocardial infarction (MI). METHODS AND RESULTS: We recruited 15
      patients with MI, 10 patients with stable angina and 10 healthy volunteers and
      measured temporal changes of MIF in plasma. Expression of MIF, matrix
      metalloproteinase-9 (MMP-9) and interleukin-6 (IL-6) in cultured peripheral blood
      mononuclear cells (PBMCs) and the media were measured by ELISA or real-time PCR.
      Compared to controls, plasma levels of MIF and IL-6 were significantly elevated
      at admission and 72 h post-MI. In contrast, expression of MIF, MMP-9 and IL-6 by
      PBMCs from MI patients was unchanged at admission, but significantly increased at
      72 h. Addition of MIF activated cultured PBMCs by upregulating expression of
      inflammatory molecules and also synergistically enhanced stimulatory action of IL
      1beta which were inhibited by anti-MIF interventions. In a mouse MI model we
      observed similar changes in circulating MIF as seen in patients, with reciprocal
      significant increases in plasma MIF and reduction of MIF content in the infarct
      myocardium at 3 h after MI. MIF content in the infarct myocardium was restored at
      72 h post-MI and was associated with robust macrophage infiltration. Further,
      anti-MIF intervention significantly reduced inflammatory cell infiltration and
      expression of monocyte chemoattractant protein-1 at 24 h and incidence of cardiac
      rupture in mice post-MI. CONCLUSION: MI leads to a rapid release of MIF from the
      myocardium into circulation. Subsequently MIF facilitates PBMC production of pro
      inflammatory mediators and myocardial inflammatory infiltration. Attenuation of
      these events, and post-MI cardiac rupture, by anti-MIF interventions suggests
      that MIF could be a potential therapeutic target following MI.

PMID- 24098446
TI  - Tissue distribution and efficacy of gold nanorods coupled with laser induced
      photoplasmonic therapy in ehrlich carcinoma solid tumor model.
AB  - Gold nanorods (GNR) within tumor microregions are characterized by their ability
      to absorb near IR light and emit heat in what is called photoplasmonic effect.
      Yet, the efficacy of nanoparticles is limited due to intratumoral tissue
      distribution reasons. In addition, distribution of GNRs to normal tissue might
      result in non specific toxicity. In the current study, we are assessing the
      intratumoral and tissue distribution of PEGylated GNRs on the top of its
      antitumor characteristics when given intravenously or intratumoral to solid tumor
      bearing mice and coupled with laser photoplasmonic sessions. PEGylated GNRs with
      a longitudinal size of less than 100 nm were prepared with aspect ratio of 4.6
      showing strong surface plasmon absorption at wavelength 800 nm. Pharmacokinetics
      of GNR after single I.V. administration (0.1 mg/kg) showed very short systemic
      circulating time (less than 3 h). On the other hand, tissue distribution of I.V.
      GNR (0.1 mg/kg) to normal animals showed preferential deposition in spleen
      tissue. Repeated administration of I.V. GNR resulted in preferential accumulation
      in both liver and spleen tissues. In addition, I.V. administration of GNR to
      Ehrlich carcinoma tumor bearing mice resulted in similar tissue distribution;
      tumor accumulation and anti-tumor effect compared to intratumoral administration.
      In conclusion, the concentration of GNR achieved within tumors microregions after
      I.V. administration was comparable to I.T. administration and sufficient to
      elicit tumoral growth arrest when coupled with laser-aided photoplasmonic
      treatment. 

PMID- 24098447
TI  - Dual role of miR-21 in CD4+ T-cells: activation-induced miR-21 supports survival
      of memory T-cells and regulates CCR7 expression in naive T-cells.
AB  - Immune cell-type specific miRNA expression patterns have been described but the
      detailed role of single miRNAs in the function of T-cells remains largely
      unknown. We investigated the role of miR-21 in the function of primary human CD4+
      T-cells. MiR-21 is substantially expressed in T-cells with a memory phenotype,
      and is robustly upregulated upon alphaCD3/CD28 activation of both naive and
      memory T-cells. By inhibiting the endogenous miR-21 function in activated naive
      and memory T-cells, we showed that miR-21 regulates fundamentally different
      aspects of T-cell biology, depending on the differentiation status of the T-cell.
      Stable inhibition of miR-21 function in activated memory T-cells led to growth
      disadvantage and apoptosis, indicating that the survival of memory T-cells
      depends on miR-21 function. In contrast, stable inhibition of miR-21 function in
      activated naive T-cells did not result in growth disadvantage, but led to a
      significant induction of CCR7 protein expression. Direct interaction between CCR7
      and miR-21 was confirmed in a dual luciferase reporter assay. Our data provide
      evidence for a dual role of miR-21 in CD4+ T cells; Regulation of T-cell survival
      is confined to activated memory T-cells, while modulation of potential homing
      properties, through downregulation of CCR7 protein expression, is observed in
      activated naive T-cells. 

PMID- 24098448
TI  - Structural insights into neutrophilic migration revealed by the crystal structure
      of the chemokine receptor CXCR2 in complex with the first PDZ domain of NHERF1.
AB  - Neutrophil plays an essential role in host defense against infection, but
      uncontrolled neutrophilic infiltration can cause inflammation and severe
      epithelial damage. We recently showed that CXCR2 formed a signaling complex with
      NHERF1 and PLC-2, and that the formation of this complex was required for
      intracellular calcium mobilization and neutrophilic transepithelial migration. To
      uncover the structural basis of the complex formation, we report here the crystal
      structure of the NHERF1 PDZ1 domain in complex with the C-terminal sequence of
      CXCR2 at 1.16 A resolution. The structure reveals that the CXCR2 peptide binds to
      PDZ1 in an extended conformation with the last four residues making specific side
      chain interactions. Remarkably, comparison of the structure to previously studied
      PDZ1 domains has allowed the identification of PDZ1 ligand-specific interactions
      and the mechanisms that govern PDZ1 target selection diversities. In addition, we
      show that CXCR2 can bind both NHERF1 PDZ1 and PDZ2 in pulldown experiments,
      consistent with the observation that the peptide binding pockets of these two PDZ
      domains are highly structurally conserved. The results of this study therefore
      provide structural basis for the CXCR2-mediated neutrophilic migration and could
      have important clinical applications in the prevention and treatment of numerous
      neutrophil-dependent inflammatory disorders. 

PMID- 24098449
TI  - Delays in appropriate antibiotic therapy for gram-negative bloodstream
      infections: a multicenter, community hospital study.
AB  - BACKGROUND: Gram-negative bacterial bloodstream infection (BSI) is a serious
      condition with estimated 30% mortality. Clinical outcomes for patients with
      severe infections improve when antibiotics are appropriately chosen and given
      early. The objective of this study was to estimate the association of prior
      healthcare exposure on time to appropriate antibiotic therapy in patients with
      gram-negative BSI. METHOD: We performed a multicenter cohort study of adult,
      hospitalized patients with gram-negative BSI using time to event analysis in nine
      community hospitals from 2003-2006. Event time was defined as the first
      administration of an antibiotic with in vitro activity against the infecting
      organism. Healthcare exposure status was categorized as community-acquired,
      healthcare-associated, or hospital-acquired. Time to appropriate therapy among
      groups of patients with differing healthcare exposure status was assessed using
      Kaplan-Meier analyses and multivariate Cox proportional hazards models. RESULTS:
      The cohort included 578 patients with gram-negative BSI, including 320 (55%)
      healthcare-associated, 217 (38%) community-acquired, and 41 (7%) hospital
      acquired infections. 529 (92%) patients received an appropriate antibiotic during
      their hospitalization. Time to appropriate therapy was significantly different
      among the groups of healthcare exposure status (log-rank p=0.02). Time to first
      antibiotic administration regardless of drug appropriateness was not different
      between groups (p=0.3). The unadjusted hazard ratios (HR) (95% confidence
      interval) were 0.80 (0.65-0.98) for healthcare-associated and 0.72 (0.63-0.82)
      for hospital-acquired, relative to patients with community-acquired BSI. In
      multivariable analysis, interaction was found between the main effect and
      baseline Charlson comorbidity index. When Charlson index was 3, adjusted HRs were
      0.66 (0.48-0.92) for healthcare-associated and 0.57 (0.44-0.75) for hospital
      acquired, relative to patients with community-acquired infections. CONCLUSIONS:
      Patients with healthcare-associated or hospital-acquired BSI experienced delays
      in receipt of appropriate antibiotics for gram-negative BSI compared to patients
      with community-acquired BSI. This difference was not due to delayed initiation of
      antibiotic therapy, but due to the inappropriate choice of antibiotic.

PMID- 24098450
TI  - Lumican - derived peptides inhibit melanoma cell growth and migration.
AB  - Lumican, a small leucine-rich proteoglycan of the extracellular matrix, presents
      potent anti-tumor properties. Previous works from our group showed that lumican
      inhibited melanoma cell migration and tumor growth in vitro and in vivo. Melanoma
      cells adhered to lumican, resulting in a remodeling of their actin cytoskeleton
      and preventing their migration. In addition, we identified a sequence of 17 amino
      acids within the lumican core protein, named lumcorin, which was able to inhibit
      cell chemotaxis and reproduce anti-migratory effect of lumican in vitro. The aim
      of the present study was to characterize the anti-tumor mechanism of action of
      lumcorin. Lumcorin significantly decreased the growth in monolayer and in soft
      agar of two melanoma cell lines - mice B16F1 and human SK-MEL-28 cells - in
      comparison to controls. Addition of lumcorin to serum free medium significantly
      inhibited spontaneous motility of these two melanoma cell lines. To characterize
      the mechanisms involved in the inhibition of cell migration by lumcorin, the
      status of the phosphorylation/dephosphorylation of proteins was examined.
      Inhibition of focal adhesion kinase phosphorylation was observed in presence of
      lumcorin. Since cancer cells have been shown to migrate and to invade by
      mechanisms that involve matrix metalloproteinases (MMPs), the expression and
      activity of MMPs were analyzed. Lumcorin induced an accumulation of an
      intermediate form of MMP-14 (~59kDa), and inhibited MMP-14 activity.
      Additionally, we identified a short, 10 amino acids peptide within lumcorin
      sequence, which was able to reproduce its anti-tumor effect on melanoma cells.
      This peptide may have potential pharmacological applications. 

PMID- 24098451
TI  - Fucosylated but not sialylated milk oligosaccharides diminish colon motor
      contractions.
AB  - Human milk oligosaccharides (HMO) are being studied by different groups exploring
      a broad range of potential beneficial effects to the breastfed infant. Many of
      these effects have been attributed to a growth promotion effect on certain gut
      organisms such as bifidobacteria. Additionally, evidence indicates that HMO are
      able to directly promote positive changes in gut epithelium and immune responses
      under certain conditions. This study utilizes a standardized ex vivo murine colon
      preparation to examine the effects of sialylated, fucosylated and other HMO on
      gut motor contractions. Only the fucosylated molecules, 2'FL and 3'FL, decreased
      contractility in a concentration dependent fashion. On the basis of IC50
      determinations 3'FL was greater than 2 times more effective than 2'FL. The HMO
      3'SL and 6'SL, lacto-N-neotetraose (LNnT), and galactooligosaccharides (GOS)
      elicited no effects. Lactose was used as a negative control. Fucosylation seems
      to underlie this functional regulation of gut contractility by oligosaccharides,
      and L-fucose, while it was also capable of reducing contractility, was
      substantially less effective than 3'FL and 2'FL. These results suggest that
      specific HMO are unlikely to be having these effects via bifidogenesis, but
      though direct action on neuronally dependent gut migrating motor complexes is
      likely and fucosylation is important in providing this function, we cannot
      conclusively shown that this is not indirectly mediated. Furthermore they support
      the possibility that fucosylated sugars and fucose might be useful as therapeutic
      or preventative adjuncts in disorders of gut motility, and possibly also have
      beneficial central nervous system effects. 

PMID- 24098452
TI  - miR-125b acts as a tumor suppressor in breast tumorigenesis via its novel direct
      targets ENPEP, CK2-alpha, CCNJ, and MEGF9.
AB  - MicroRNAs (miRNAs) play important roles in diverse biological processes and are
      emerging as key regulators of tumorigenesis and tumor progression. To explore the
      dysregulation of miRNAs in breast cancer, a genome-wide expression profiling of
      939 miRNAs was performed in 50 breast cancer patients. A total of 35 miRNAs were
      aberrantly expressed between breast cancer tissue and adjacent normal breast
      tissue and several novel miRNAs were identified as potential oncogenes or tumor
      suppressor miRNAs in breast tumorigenesis. miR-125b exhibited the largest
      decrease in expression. Enforced miR-125b expression in mammary cells decreased
      cell proliferation by inducing G2/M cell cycle arrest and reduced anchorage
      independent cell growth of cells of mammary origin. miR-125b was found to perform
      its tumor suppressor function via the direct targeting of the 3'-UTRs of ENPEP,
      CK2-alpha, CCNJ, and MEGF9 mRNAs. Silencing these miR-125b targets mimicked the
      biological effects of miR-125b overexpression, confirming that they are modulated
      by miR-125b. Analysis of ENPEP, CK2-alpha, CCNJ, and MEGF9 protein expression in
      breast cancer patients revealed that they were overexpressed in 56%, 40-56%, 20%,
      and 32% of the tumors, respectively. The expression of ENPEP and CK2-alpha was
      inversely correlated with miR-125b expression in breast tumors, indicating the
      relevance of these potential oncogenic proteins in breast cancer patients. Our
      results support a prognostic role for CK2-alpha, whose expression may help
      clinicians predict breast tumor aggressiveness. In particular, our results show
      that restoration of miR-125b expression or knockdown of ENPEP, CK2-alpha, CCNJ,
      or MEGF9 may provide novel approaches for the treatment of breast cancer. 

PMID- 24098453
TI  - Zfat-deficiency results in a loss of CD3zeta phosphorylation with dysregulation
      of ERK and Egr activities leading to impaired positive selection.
AB  - The human ZFAT gene was originally identified as a susceptibility gene for
      autoimmune thyroid disease. Mouse Zfat is a critical transcriptional regulator
      for primitive hematopoiesis and required for peripheral T cell homeostasis.
      However, its physiological roles in T cell development remain poorly understood.
      Here, we generated Zfat (f/f)-LckCre mice and demonstrated that T cell-specific
      Zfat-deletion in Zfat (f/f)-LckCre mice resulted in a reduction in the number of
      CD4(+)CD8(+)double-positive (DP) cells, CD4(+)single positive cells and
      CD8(+)single positive cells. Indeed, in Zfat (f/f)-LckCre DP cells, positive
      selection was severely impaired. Defects of positive selection in Zfat-deficient
      thymocytes were not restored in the presence of the exogenous TCR by using TCR
      transgenic mice. Furthermore, Zfat-deficient DP cells showed a loss of CD3zeta
      phosphorylation in response to T cell antigen receptor (TCR)-stimulation
      concomitant with dysregulation of extracellular signal-related kinase (ERK) and
      early growth response protein (Egr) activities. These results demonstrate that
      Zfat is required for proper regulation of the TCR-proximal signalings, and is a
      crucial molecule for positive selection through ERK and Egr activities, thus
      suggesting that a full understanding of the precise molecular mechanisms of Zfat
      will provide deeper insight into T cell development and immune regulation. 

PMID- 24098454
TI  - The presence of CXCR4-using HIV-1 prior to start of antiretroviral therapy is an
      independent predictor of delayed viral suppression.
AB  - The emergence of CXCR4-using HIV variants (X4-HIV) is associated with accelerated
      disease progression in the absence of antiretroviral therapy. However, the effect
      of X4-HIV variants on the treatment response remains unclear. Here we determined
      whether the presence of X4-HIV variants influenced the time to undetectable viral
      load and CD4+ T cell reconstitution after initiation of cART in 732 patients. The
      presence of X4-HIV variants was determined by MT-2 assay prior to cART initiation
      and viral load and CD4+ T cell counts were analyzed every 3 to 6 months during a
      three year follow-up period. Kaplan-Meier and Cox proportional hazard analyses
      were performed to compare time to viral suppression and the absolute CD4+ T cell
      counts and increases in CD4+ T cell counts during follow-up were compared for
      patients with and without X4-HIV at start of cART. Patients harboring X4-HIV
      variants at baseline showed a delay in time to achieve viral suppression below
      the viral load detection limit. This delay in viral suppression was independently
      associated with high viral load and the presence of X4-HIV variants. Furthermore,
      the absolute CD4+ T cell counts were significantly lower in patients harboring X4
      HIV variants at all time points during follow-up. However, no differences were
      observed in the increase in absolute CD4+ T cell numbers after treatment
      initiation, indicating that the reconstitution of CD4+ T cells is independent of
      the presence of X4-HIV variants. The emergence of X4-HIV has been associated with
      an accelerated CD4+ T cell decline during the natural course of infection and
      therefore, patients who develop X4-HIV variants may benefit from earlier
      treatment initiation in order to obtain faster reconstitution of the CD4+ T cell
      population to normal levels. 

PMID- 24098455
TI  - In vivo T cell activation induces the formation of CD209(+) PDL-2(+) dendritic
      cells.
AB  - Two critical functions of dendritic cells (DC) are to activate and functionally
      polarize T cells. Activated T cells can, in turn, influence DC maturation,
      although their effect on de novo DC development is poorly understood. Here we
      report that activation of T cells in mice, with either an anti-CD3 antibody or
      super antigen, drives the rapid formation of CD209(+)CD11b(+)CD11c(+) MHC II(+)
      DC from monocytic precursors (Mo-DC). GM-CSF is produced by T cells following
      activation, but surprisingly, it is not required for the formation of CD209(+) Mo
      DC. CD40L, however, is critical for the full induction of Mo-DC following T cell
      activation. T cell induced CD209(+) Mo-DC are comparable to conventional CD209(-)
      DC in their ability to stimulate T cell proliferation. However, in contrast to
      conventional CD209(-) DC, CD209(+) Mo-DC fail to effectively polarize T cells, as
      indicated by a paucity of T cell cytokine production. The inability of CD209(+)
      Mo-DC to polarize T cells is partly explained by increased expression of PDL-2,
      since blockade of this molecule restores some polarizing capacity to the Mo-DC.
      These findings expand the range of signals capable of driving Mo-DC
      differentiation in vivo beyond exogenous microbial factors to include endogenous
      factors produced following T cell activation. 

PMID- 24098456
TI  - 2,3,7,8-tetrachlorodibenzo-p-dioxin slows the progression of experimental
      cutaneous Leishmaniasis in susceptible BALB/c and SCID mice.
AB  - In a model of experimental cutaneous leishmaniasis, pre-exposure of Leishmania
      major-resistant mice to 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD), an aryl
      hydrocarbon receptor agonist, causes suppression of the protective anti-parasite
      T helper 1 response while paradoxically also reducing parasite burdens in those
      animals. In this study, we examined if TCDD exposure could also reduce parasite
      burdens in L. major-susceptible BALB/c mice. In the highest dose group (160
      ug/Kg), TCDD treatment caused a significant reduction of parasite burdens by 10
      fold after three weeks while also causing a significant lymphoid atrophy
      indicating suppression of the non-protective T helper 2 response. A dose
      dependent delay of foot lesion progression was also observed such that lesion
      size in the highest dose group was less than half that of controls after 35 days
      of infection. Importantly, although TCDD exposure initially reduced disease
      severity and prolonged the course of disease by as much as three fold in some
      animals, this effect was transitory and TCDD did not induce resistance to L.
      major infection. Because TCDD exposure reduced L. major burdens in both resistant
      and susceptible mice, we hypothesized that TCDD reduces L. major burdens in mice
      by a mechanism that does not involve adaptive immunity. To test this, severe
      combined immunodeficient (SCID) mice were used. In mice infected with a moderate
      number of L. major (10,000), TCDD treatment caused a time- and dose-dependent
      decrease of parasite burdens by nearly 100-fold after six weeks in the highest
      dose group (200 ug/Kg). A significant and dose-dependent delay of foot lesion
      progression was also observed in these animals. These results indicate that TCDD
      exposure can reduce the severity of leishmanial disease in mice independent of
      adaptive immunity. 

PMID- 24098457
TI  - Evaluation of glutathione S-transferase GSTM1 and GSTT1 deletion polymorphisms on
      type-2 diabetes mellitus risk.
AB  - BACKGROUND: Due to the activity of GSTs in the detoxification of oxidative stress
      products, deletion polymorphisms of GSTM1 and GSTT1 may contribute to
      susceptibility to T2DM, since B-cells express very low levels of antioxidant
      enzymes. Recently, some studies have shown an association between GSTM1
      null/GSTT1-null genotypes and an increased susceptibility to T2DM. A relationship
      between these polymorphisms and changes in the clinical parameters of diabetic
      patients has also been investigated. However, the results diverge considerably
      among the studies. Thus, this case-control study was designed to contribute to
      existing knowledge, as there are no studies on this issue performed in the
      Brazilian population. METHODS AND FINDINGS: A total of 120 patients and 147
      healthy individuals were included in this study. GSTT1 and GSTM1 deletion
      polymorphisms were genotyped by multiplex SYBR Green Real-Time PCR. The GSTT1
      null genotype conferred a 3.2-fold increased risk to T2DM relative to the present
      genotype. There was no association between GSTM1-null and T2DM risk. In diabetic
      patients, GSTT1-null conferred higher levels of triglycerides and VLDL
      cholesterol, while GSTM1-null was associated with increased levels of fasting
      blood glucose, glycated hemoglobin and blood pressure. We emphasized a necessity
      for applying log-linear analysis in order to explore an interaction between these
      polymorphisms properly. CONCLUSION: These results suggest that the GSTT1
      polymorphism may play an important role in the pathogenesis of T2DM in the
      Brazilian population. This gene could then be added to a set of genetic markers
      to identify individuals with an increased risk for developing T2DM and
      complications associated with dyslipidemia in diabetic patients. Although there
      was no association of GSTM1 deletion polymorphism with susceptibility to T2DM,
      the influence of this polymorphism on important clinical parameters related to
      glycemia and blood pressure levels was verified. This finding suggests that both
      GSTM1-null and GSTT1-null may contribute to the clinical course of T2DM patients.

PMID- 24098458
TI  - Ca(2+) efflux is involved in cinnamaldehyde-induced growth inhibition of
      Phytophthora capsici.
AB  - As a destructive fungus-like plant pathogen, the oomycete Phytophthoracapsici is
      unable to synthesize its own ergosterol as the potential target of fungicide
      cinnamaldehyde (CA). In this study, CA exerted efficient inhibitory effects on
      both mycelial growth (EC50=0.75 mM) and zoospore germination (MIC=0.4 mM) of P.
      capsici. CA-induced immediate Ca(2+) efflux from zoospores could be confirmed by
      the rapid decrease in intracellular Ca(2+) content determined by using Fluo-3 AM
      and the increase in extracellular Ca(2+) concentration determined by using ICP
      AES (inductively coupled plasma atomic emission spectrometry). Blocking Ca(2+)
      influx with ruthenium red and verapamil led to a higher level of CA-induced
      Ca(2+) efflux, suggesting the simultaneous occurrence of Ca(2+) influx along with
      the Ca(2+) efflux under CA exposure. Further results showed that EGTA-induced
      decrease in intracellular Ca(2+) gave rise to the impaired vitality of P. capsici
      while the addition of exogenous Ca(2+) could suppress the growth inhibitory
      effect of CA. These results suggested that Ca(2+) efflux played an important role
      in CA-induced growth inhibition of P. capsici. The application of 3-phenyl-1
      propanal, a CA analog without alpha,beta- unsaturated bond, resulted in a marked
      Ca(2+) influx in zoospores but did not show any growth inhibitory effects. In
      addition, exogenous cysteine, an antagonist against the Michael addition (the
      nucleophilic addition of a carbanion or another nucleophile) between CA and its
      targets, could attenuate CA-induced growth inhibition of P. capsici by
      suppressing Ca(2+) efflux. Our results suggest that CA inhibits the growth of P.
      capsici by stimulating a transient Ca(2+) efflux via Michael addition, which
      provides important new insights into the antimicrobial action of CA. 

PMID- 24098459
TI  - Defining the vulnerable period for re-establishment of Clostridium difficile
      colonization after treatment of C. difficile infection with oral vancomycin or
      metronidazole.
AB  - BACKGROUND: Clostridium difficile is an anaerobic, spore-forming bacterium that
      is the most common cause of healthcare-associated diarrhea in developed
      countries. A significant proportion of patients receiving oral vancomycin or
      metronidazole for treatment of Clostridium difficile infection (CDI) develop
      recurrences. However, the period of vulnerability to re-establishment of
      colonization by C. difficile after therapy is not well defined. PRINCIPAL
      FINDINGS: In a prospective study of CDI patients, we demonstrated that most
      vancomycin-treated patients maintained inhibitory concentrations of vancomycin in
      stool for 4 to 5 days after therapy, whereas metronidazole was only detectable
      during therapy. From the time of elimination of the antibiotics to 14 to 21 days
      after therapy, a majority of stool suspensions supported growth of C. difficile
      and deep 16S rRNA sequencing demonstrated persistent marked alteration of the
      indigenous microbiota. By 21 to 28 days after completion of CDI treatment, a
      majority of stool suspensions inhibited growth of C. difficile and there was
      evidence of some recovery of the microbiota. CONCLUSIONS: These data demonstrate
      that there is a vulnerable period for re-establishment of C. difficile
      colonization after CDI treatment that begins within a few days after
      discontinuation of treatment and extends for about 3 weeks in most patients.

PMID- 24098460
TI  - Oral community interactions of Filifactor alocis in vitro.
AB  - Filifactor alocis is a gram positive anaerobe that is emerging as an important
      periodontal pathogen. In the oral cavity F. alocis colonizes polymicrobial
      biofilm communities; however, little is known regarding the nature of the
      interactions between F. alocis and other oral biofilm bacteria. Here we
      investigate the community interactions of two strains of F. alocis with
      Streptococcus gordonii, Fusobacterium nucleatum, Porphyromonas gingivalis and
      Aggregatibacter actinomycetemcomitans, organisms with differing pathogenic
      potential in the oral cavity. In an in vitro community development model, S.
      gordonii was antagonistic to the accumulation of F. alocis into a dual species
      community. In contrast, F. nucleatum and the type strain of F. alocis formed a
      synergistic partnership. Accumulation of a low passage isolate of F. alocis was
      also enhanced by F. nucleatum. In three species communities of S. gordonii, F.
      nucleatum and F. alocis, the antagonistic effects of S. gordonii superseded the
      synergistic effects of F. nucleatum toward F. alocis. The interaction between A.
      actinomycetemcomitans and F. alocis was strain specific and A.
      actinomycetemcomitans could either stimulate F. alocis accumulation or have no
      effect depending on the strain. P. gingivalis and F. alocis formed heterotypic
      communities with the amount of P. gingivalis greater than in the absence of F.
      alocis. However, while P. gingivalis benefited from the relationship, levels of
      F. alocis in the dual species community were lower compared to F. alocis alone.
      The inhibitory effect of P. gingivalis toward F. alocis was dependent, at least
      partially, on the presence of the Mfa1 fimbrial subunit. In addition, AI-2
      production by P. gingivalis helped maintain levels of F. alocis. Collectively,
      these results show that the pattern of F. alocis colonization will be dictated by
      the spatial composition of microbial microenvironments, and that the organism may
      preferentially accumulate at sites rich in F. nucleatum. 

PMID- 24098461
TI  - Tuberculosis in healthcare workers and infection control measures at primary
      healthcare facilities in South Africa.
AB  - BACKGROUND: Challenges exist regarding TB infection control and TB in hospital
      based healthcare workers in South Africa. However, few studies report on TB in
      non-hospital based healthcare workers such as primary or community healthcare
      workers. Our objectives were to investigate the implementation of TB infection
      control measures at primary healthcare facilities, the smear positive TB
      incidence rate amongst primary healthcare workers and the association between TB
      infection control measures and all types of TB in healthcare workers. METHODS:
      One hundred and thirty three primary healthcare facilities were visited in five
      provinces of South Africa in 2009. At each facility, a TB infection control audit
      and facility questionnaire were completed. The number of healthcare workers who
      had had TB during the past three years was obtained. RESULTS: The standardised
      incidence ratio of smear positive TB in primary healthcare workers indicated an
      incidence rate of more than double that of the general population. In a
      univariable logistic regression, the infection control audit score was
      significantly associated with reported cases of TB in healthcare workers
      (OR=1.04, 95%CI 1.01-1.08, p=0.02) as was the number of staff (OR=3.78, 95%CI
      1.77-8.08). In the multivariable analysis, the number of staff remained
      significantly associated with TB in healthcare workers (OR=3.33, 95%CI 1.37
      8.08). CONCLUSION: The high rate of TB in healthcare workers suggests a
      substantial nosocomial transmission risk, but the infection control audit tool
      which was used did not perform adequately as a measure of this risk. Infection
      control measures should be monitored by validated tools developed and tested
      locally. Different strategies, such as routine surveillance systems, could be
      used to evaluate the burden of TB in healthcare workers in order to calculate TB
      incidence, monitor trends and implement interventions to decrease occupational
      TB.

PMID- 24098462
TI  - The jagged-2/notch-1/hes-1 pathway is involved in intestinal epithelium
      regeneration after intestinal ischemia-reperfusion injury.
AB  - BACKGROUND: Notch signaling plays a critical role in the maintenance of
      intestinal crypt epithelial cell proliferation. The aim of this study was to
      investigate the role of Notch signaling in the proliferation and regeneration of
      intestinal epithelium after intestinal ischemia reperfusion (I/R) injury.
      METHODS: Male Sprague-Dawley rats were subjected to sham operation or I/R by
      occlusion of the superior mesenteric artery (SMA) for 20 min. Intestinal tissue
      samples were collected at 0, 1, 2, 4, and 6 h after reperfusion. Proliferation of
      the intestinal epithelium was evaluated by immunohistochemical staining of
      proliferating nuclear antigen (PCNA). The mRNA and protein expression levels of
      Notch signaling components were examined using Real-time PCR and Western blot
      analyses. Immunofluorescence was also performed to detect the expression and
      location of Jagged-2, cleaved Notch-1, and Hes-1 in the intestine. Finally, the
      gamma-secretase inhibitor DAPT and the siRNA for Jagged-2 and Hes-1 were applied
      to investigate the functional role of Notch signaling in the proliferation of
      intestinal epithelial cells in an in vitro IEC-6 culture system. RESULTS: I/R
      injury caused increased intestinal crypt epithelial cell proliferation and
      increased mRNA and protein expression of Jagged-2, Notch-1, and Hes-1. The
      immunofluorescence results further confirmed increased protein expression of
      Jagged-2, cleaved Notch-1, and Hes-1 in the intestinal crypts. The inhibition of
      Notch signaling with DAPT and the suppression of Jagged-2 and Hes-1 expression
      using siRNA both significantly inhibited the proliferation of IEC-6 cells.
      CONCLUSION: The Jagged-2/Notch-1/Hes-1 signaling pathway is involved in
      intestinal epithelium regeneration early after I/R injury by increasing crypt
      epithelial cell proliferation.

PMID- 24098463
TI  - Expression of human endogenous retrovirus-w including syncytin-1 in cutaneous T
      cell lymphoma.
AB  - The pathomechanism of mycosis fungoides (MF), the most common type of primary
      cutaneous T-cell lymphomas (CTCLs) and a malignancy of non-recirculating, skin
      resident T-cells, is unknown albeit underlying viral infections have been sought
      for. Human endogenous retroviruses (HERVs) are ancient retroviral sequences in
      the human genome and their transcription is often deregulated in cancers. We
      explored the transcriptional activity of HERV sequences in a total of 34 samples
      comprising MF and psoriasis skin lesions, as well as corresponding non-malignant
      skin using a retrovirus-specific microarray and quantitative RT-PCR. To identify
      active HERV-W loci, we cloned the HERV-W specific RT-PCR products, sequenced the
      cDNA clones and assigned the sequences to HERV-W loci. Finally, we used
      immunohistochemistry on MF patient and non-malignant inflammatory skin samples to
      confirm specific HERV-encoded protein expression. Firstly, a distinct, skin
      specific transcription profile consisting of five constitutively active HERV
      groups was established. Although individual variability was common, HERV-W showed
      significantly increased transcription in MF lesions compared to clinically intact
      skin from the same patient. Predominantly transcribed HERV-W loci were found to
      be located in chromosomes 6q21 and 7q21.2, chromosomal regions typically altered
      in CTCL. Surprisingly, we also found the expression of 7q21.2/ERVWE1-encoded
      Syncytin-1 (Env) protein in MF biopsies and expression of Syncytin-1 was seen in
      malignant lymphocytes, especially in the epidermotropic ones, in 15 of 30 cases
      studied. Most importantly, no Syncytin-1 expression was detected in inflammatory
      dermatosis (Lichen ruber planus) with skin-homing, non-malignant T lymphocytes.
      The expression of ERVWE1 mRNA was further confirmed in 3/7 MF lesions analyzed.
      Our observations strengthen the association between activated HERVs and cancer.
      The study offers a new perspective into the pathogenesis of CTCL since we
      demonstrate that differences in HERV-W transcription levels between lesional MF
      and non-malignant skin are significant, and that ERVWE1-encoded Syncytin-1 is
      expressed in MF lymphoma cells. 

PMID- 24098464
TI  - Identification of microRNA-Like RNAs in the filamentous fungus Trichoderma reesei
      by solexa sequencing.
AB  - microRNAs (miRNAs) are non-coding small RNAs (sRNAs) capable of negatively
      regulating gene expression. Recently, microRNA-like small RNAs (milRNAs) were
      discovered in several filamentous fungi but not yet in Trichoderma reesei, an
      industrial filamentous fungus that can secrete abundant hydrolases. To explore
      the presence of milRNA in T. reesei and evaluate their expression under induction
      of cellulose, two T. reesei sRNA libraries of cellulose induction (IN) and non
      induction (CON) were generated and sequenced using Solexa sequencing technology.
      A total of 726 and 631 sRNAs were obtained from the IN and CON samples,
      respectively. Global expression analysis showed an extensively differential
      expression of sRNAs in T. reesei under the two conditions. Thirteen predicted
      milRNAs were identified in T. reesei based on the short hairpin structure
      analysis. The milRNA profiles obtained in deep sequencing were further validated
      by RT-qPCR assay. Computational analysis predicted a number of potential targets
      relating to many processes including regulation of enzyme expression. The
      presence and differential expression of T. reesei milRNAs imply that milRNA might
      play a role in T. reesei growth and cellulase induction. This work lays
      foundation for further functional study of fungal milRNAs and their industrial
      application. 

PMID- 24098465
TI  - A polymorphic 3'UTR element in ATP1B1 regulates alternative polyadenylation and
      is associated with blood pressure.
AB  - Although variants in many genes have previously been shown to be associated with
      blood pressure (BP) levels, the molecular mechanism underlying these associations
      are mostly unknown. We identified a multi-allelic T-rich sequence (TRS) in the
      3'UTR of ATP1B1 that varies in length and sequence composition (T22-27 and T12GT
      3GT6). The 3'UTR of ATP1B1 contains 2 functional polyadenylation signals and the
      TRS is downstream of the proximal polyadenylation site (A2). Therefore, we
      hypothesized that alleles of this TRS might influence ATP1B1 expression by
      regulating alternative polyadenylation. In vitro, the T12GT 3GT6 allele increases
      polyadenylation at the A2 polyadenylation site as compared to the T23 allele.
      Consistent with our hypothesis, the relative abundance of the A2-polyadenylated
      ATP1B1 mRNA was higher in human kidneys with at least one copy of the T12GT 3GT6
      allele than in those lacking this allele. The T12GT 3GT6 allele is also
      associated with higher systolic BP (beta = 3.3 mmHg, p = 0.014) and diastolic BP
      (beta = 2.4 mmHg, p = 0.003) in a European-American population. Therefore, we
      have identified a novel multi-allelic TRS in the 3'UTR of ATP1B1 that is
      associated with higher BP and may mediate its effect by regulating the
      polyadenylation of the ATP1B1 mRNA. 

PMID- 24098466
TI  - The heme oxygenase-1 inducer THI-56 negatively regulates iNOS expression and
      HMGB1 release in LPS-activated RAW 264.7 cells and CLP-induced septic mice.
AB  - The nuclear DNA binding protein high mobility group box 1 (HMGB1) has recently
      been suggested to act as a late mediator of septic shock. The effect of ((S)-6,7
      dihydroxy-1-(4-hydroxynaphthylmethyl)-1,2,3,4-tetrahydroisoquinoline alkaloid,
      also known as THI-56, in an experimental model of sepsis was investigated. THI-56
      exhibited potent anti-inflammatory properties in response to LPS in RAW 264.7
      cells. In particular, THI-56 significantly inhibited the expression of inducible
      nitric oxide synthase (iNOS) and the release of HMGB1 in activated macrophages.
      THI-56 activated NE-F2-regulated factor 2 (Nrf-2)/heme oxygenase 1 (HO-1). The
      specific knockdown of the HO-1 gene by HO-1 siRNA significantly reversed the
      inhibitory effects of THI-56 on iNOS expression and HMGB1 release in LPS
      stimulated macrophages. Importantly, THI-56 administration protected animals from
      death induced by either a lethal dose of LPS or cecal ligation and puncture
      (CLP). Furthermore, the ALT, AST, BUN, creatinine, and HMGB1 levels in the blood
      were significantly increased in CLP-induced septic mice, and the administration
      of THI-56 reduced these levels in a concentration-dependent and zinc
      protoporphyrin IX (ZnPPIX)-sensitive manner. In addition, the administration of
      THI-56 significantly ameliorated not only lung damage but also macrophage
      infiltration in the livers of CLP-induced septic mice, and these effects were
      also abrogated in the presence of ZnPPIX. Thus, we conclude that THI-56
      significantly attenuates the proinflammatory response induced by LPS and reduces
      organ damage in a CLP-induced sepsis model through the upregulation of Nrf-2/HO
      1. 

PMID- 24098467
TI  - Pitavastatin and Atorvastatin double-blind randomized comPArative study among
      hiGh-risk patients, including thOse with Type 2 diabetes mellitus, in Taiwan
      (PAPAGO-T Study).
AB  - BACKGROUND: Evidence about the efficacy and safety of statin treatment in high
      risk patients with hypercholesterolemia is available for some populations, but
      not for ethnic Chinese. To test the hypothesis that treatment with pitavastatin
      (2 mg/day) is not inferior to treatment with atorvastatin (10 mg/day) for
      reducing low-density lipoprotein cholesterol (LDL-C), a 12-week multicenter
      collaborative randomized parallel-group comparative study of high-risk ethnic
      Chinese patients with hypercholesterolemia was conducted in Taiwan. In addition,
      the effects on other lipid parameters, inflammatory markers, insulin-resistance
      associated biomarkers and safety were evaluated. METHODS AND RESULTS: Between
      July 2011 and April 2012, 251 patients were screened, 225 (mean age: 58.7 +/-
      8.6; women 38.2% [86/225]) were randomized and treated with pitavastatin (n =
      112) or atorvastatin (n = 113) for 12 weeks. Baseline characteristics in both
      groups were similar, but after 12 weeks of treatment, LDL-C levels were
      significantly lower: pitavastatin group = -35.0 +/- 14.1% and atorvastatin group
      = -38.4 +/- 12.8% (both: p < 0.001). For the subgroup with diabetes mellitus (DM)
      (n = 125), LDL-C levels (-37.1 +/- 12.9% vs. -38.0 +/- 13.1%, p = 0.62) were
      similarly lowered after either pitavastatin (n = 63) or atorvastatin (n = 62)
      treatment. Triglycerides, non-high density lipoprotein cholesterol, and
      apoprotein B were similarly and significantly lower in both treatment groups. In
      non-lipid profiles, HOMA-IR and insulin levels were higher to a similar degree in
      both statin groups. Hemoglobin A1C was significantly (p = 0.001) higher in the
      atorvastatin group but not in the pitavastatin group. Both statins were well
      tolerated, and both groups had a similar low incidence of treatment-emergent
      adverse events. CONCLUSION: Both pitavastatin (2 mg/day) and atorvastatin (10
      mg/day) were well tolerated, lowered LDL-C, and improved the lipid profile to a
      comparable degree in high-risk Taiwanese patients with hypercholesterolemia.
      TRIAL REGISTRATION: ClinicalTrials.gov NCT01386853
      http://clinicaltrials.gov/ct2/show/NCT01386853?term=NCT01386853&rank=1.

PMID- 24098468
TI  - DNA methylation mediates persistent epileptiform activity in vitro and in vivo.
AB  - Epilepsy is a chronic brain disorder involving recurring seizures often
      precipitated by an earlier neuronal insult. The mechanisms that link the
      transient neuronal insult to the lasting state of epilepsy are unknown. Here we
      tested the possible role of DNA methylation in mediating long-term induction of
      epileptiform activity by transient kainic acid exposure using in vitro and in
      vivo rodent models. We analyzed changes in the gria2 gene, which encodes for the
      GluA2 subunit of the ionotropic glutamate, alpha-amino-3-hydroxy-5-methyl-4
      isoxazole proprionic acid receptor and is well documented to play a role in
      epilepsy. We show that kainic acid exposure for two hours to mouse hippocampal
      slices triggers methylation of a 5' regulatory region of the gria2 gene. Increase
      in methylation persists one week after removal of the drug, with concurrent
      suppression of gria2 mRNA expression levels. The degree of kainic acid-induced
      hypermethylation of gria2 5' region varies between individual slices and
      correlates with the changes in excitability induced by kainic acid. In a rat in
      vivo model of post kainic acid-induced epilepsy, we show similar hypermethylation
      of the 5' region of gria2. Inter-individual variations in gria2 methylation,
      correlate with the frequency and intensity of seizures among epileptic rats.
      Luciferase reporter assays support a regulatory role for methylation of gria2 5'
      region. Inhibition of DNA methylation by RG108 blocked kainic acid-induced
      hypermethylation of gria2 5' region in hippocampal slice cultures and bursting
      activity. Our results suggest that DNA methylation of such genes as gria2
      mediates persistent epileptiform activity and inter-individual differences in the
      epileptic response to neuronal insult and that pharmacological agents that block
      DNA methylation inhibit epileptiform activity raising the prospect of DNA
      methylation inhibitors in epilepsy therapeutics. 

PMID- 24098470
TI  - Up-regulation of SOX9 in sertoli cells from testiculopathic patients accounts for
      increasing anti-mullerian hormone expression via impaired androgen receptor
      signaling.
AB  - BACKGROUND: Testosterone provokes Sertoli cell maturation and represses AMH
      production. In adult patients with Sertoli-cells-only syndrome (SCOS) and
      androgen insensitivity syndrome (AIS), high level of AMH expression is detected
      in Sertoli cells due to defect of androgen/AR signaling. OBJECTIVE: We postulated
      that up-regulation of SOX9 due to impairment of androgen/AR signaling in Sertoli
      cells might explain why high level of anti-Mullerian hormone (AMH) expression
      occur in these testiculopathic patients. METHODS: Biological research of
      testicular specimens from men with azoospermia or mouse. The serum hormone levels
      were studied in 23 men with obstructive azoospermia, 33 men with SCOS azoospermia
      and 21 volunteers with normal seminograms during a period of 4 years.
      Immunohistochemical staining and reverse-transcription PCR were used to examine
      the relationships among AR, SOX9 and AMH expression in adult human and mouse
      testes. The ability of AR to repress the expression of SOX9 and AMH was evaluated
      in vitro in TM4 Sertoli cells and C3H10T1/2 cells. RESULTS: SCOS specimens showed
      up-regulation of SOX9 and AMH proteins but down-regulation of AR proteins in
      Sertoli cells. The mRNA levels of AR were significantly lower and the SOX9, AMH
      mRNA levels higher in all SCOS patients compared to controls (P< 0.05). The
      testosterone levels in the SCOS patients were within the normal range, but most
      were below the median of the controls. Furthermore, our in vitro cell line
      experiments demonstrated that androgen/AR signaling suppressed the gene and
      protein levels of AMH via repression of SOX9. CONCLUSIONS: Our data show that the
      functional androgen/AR signaling to repress SOX9 and AMH expression is essential
      for Sertoli cell maturation. Impairment of androgen/AR signaling promotes SOX9
      mediated AMH production, accounts for impairments of Sertoli cells in SCOS
      azoospermic patients.

PMID- 24098469
TI  - Creatine supplementation associated or not with strength training upon emotional
      and cognitive measures in older women: a randomized double-blind study.
AB  - PURPOSE: To assess the effects of creatine supplementation, associated or not
      with strength training, upon emotional and cognitive measures in older woman.
      METHODS: This is a 24-week, parallel-group, double-blind, randomized, placebo
      controlled trial. The individuals were randomly allocated into one of the
      following groups (n=14 each): 1) placebo, 2) creatine supplementation, 3) placebo
      associated with strength training or 4) creatine supplementation associated with
      strength training. According to their allocation, the participants were given
      creatine (4 x 5 g/d for 5 days followed by 5 g/d) or placebo (dextrose at the
      same dosage) and were strength trained or not. Cognitive function, assessed by a
      comprehensive battery of tests involving memory, selective attention, and
      inhibitory control, and emotional measures, assessed by the Geriatric Depression
      Scale, were evaluated at baseline, after 12 and 24 weeks of the intervention.
      Muscle strength and food intake were evaluated at baseline and after 24 weeks.
      RESULTS: After the 24-week intervention, both training groups (ingesting creatine
      supplementation and placebo) had significant reductions on the Geriatric
      Depression Scale scores when compared with the non-trained placebo group (p =
      0.001 and p = 0.01, respectively) and the non-trained creatine group (p < 0.001
      for both comparison). However, no significant differences were observed between
      the non-trained placebo and creatine (p = 0.60) groups, or between the trained
      placebo and creatine groups (p = 0.83). Both trained groups, irrespective of
      creatine supplementation, had better muscle strength performance than the non
      trained groups. Neither strength training nor creatine supplementation altered
      any parameter of cognitive performance. Food intake remained unchanged.
      CONCLUSION: Creatine supplementation did not promote any significant change in
      cognitive function and emotional parameters in apparently healthy older
      individuals. In addition, strength training per se improved emotional state and
      muscle strength, but not cognition, with no additive effects of creatine
      supplementation. TRIAL REGISTRATION: Clinicaltrials.gov NCT01164020.

PMID- 24098471
TI  - Are two interviews better than one? eyewitness memory across repeated cognitive
      interviews.
AB  - Eyewitnesses to a filmed event were interviewed twice using a Cognitive Interview
      to examine the effects of variations in delay between the repeated interviews
      (immediately & 2 days; immediately & 7 days; 7 & 9 days) and the identity of the
      interviewers (same or different across the two repeated interviews). Hypermnesia
      (an increase in total amount of information recalled in the repeated interview)
      occurred without any decrease in the overall accuracy. Reminiscence (the recall
      of new information in the repeated interview) was also found in all conditions
      but was least apparent in the longest delay condition, and came with little cost
      to the overall accuracy of information gathered. The number of errors, increased
      across the interviews, but the relative accuracy of participants' responses was
      unaffected. However, when accuracy was calculated based on all unique details
      provided across both interviews and compared to the accuracy of recall in just
      the first interview it was found to be slightly lower. The identity of the
      interviewer (whether the same or different across interviews) had no effects on
      the number of correct details. There was an increase in recall of new details
      with little cost to the overall accuracy of information gathered. Importantly,
      these results suggest that witnesses are unlikely to report everything they
      remember during a single Cognitive Interview, however exhaustive, and a second
      opportunity to recall information about the events in question may provide
      investigators with additional information. 

PMID- 24098473
TI  - Influence of pollen transport dynamics on sire profiles and multiple paternity in
      flowering plants.
AB  - In many flowering plants individual fruits contain a mixture of half- and full-
      siblings, reflecting pollination by several fathers. To better understand the
      mechanisms generating multiple paternity within fruits we present a theoretical
      framework linking pollen carryover with patterns of pollinator movement. This
      'sire profile' model predicts that species with more extensive pollen carryover
      will have a greater number of mates. It also predicts that flowers on large
      displays, which are often probed consecutively during a single pollinator
      visitation sequence, will have a lower effective number of mates. We compared
      these predictions with observed values for bumble bee-pollinated Mimulus ringens,
      which has restricted carryover, and hummingbird-pollinated Ipomopsis aggregata,
      which has extensive carryover. The model correctly predicted that the effective
      number of mates is much higher in the species with more extensive carryover. This
      work extends our knowledge of plant mating systems by highlighting mechanisms
      influencing the genetic composition of sibships. 

PMID- 24098472
TI  - Suppression of Alzheimer's disease-related phenotypes by geranylgeranylacetone in
      mice.
AB  - Amyloid-beta peptide (Abeta) plays an important role in the pathogenesis of
      Alzheimer's disease (AD). Abeta is generated by the secretase-mediated
      proteolysis of beta-amyloid precursor protein (APP), and cleared by enzyme
      mediated degradation and phagocytosis. Transforming growth factor (TGF)-beta1
      stimulates this phagocytosis. We recently reported that the APP23 mouse model for
      AD showed fewer AD-related phenotypes when these animals were crossed with
      transgenic mice expressing heat shock protein (HSP) 70. We here examined the
      effect of geranylgeranylacetone, an inducer of HSP70 expression, on the AD
      related phenotypes. Repeated oral administration of geranylgeranylacetone to
      APP23 mice for 9 months not only improved cognitive function but also decreased
      levels of Abeta, Abeta plaque deposition and synaptic loss. The treatment also up
      regulated the expression of an Abeta-degrading enzyme and TGF-beta1 but did not
      affect the maturation of APP and secretase activities. These outcomes were
      similar to those observed in APP23 mice genetically modified to overexpress
      HSP70. Although the repeated oral administration of geranylgeranylacetone did not
      increase the level of HSP70 in the brain, a single oral administration of
      geranylgeranylacetone significantly increased the level of HSP70 when Abeta was
      concomitantly injected directly into the hippocampus. Since geranylgeranylacetone
      has already been approved for use as an anti-ulcer drug and its safety in humans
      has been confirmed, we propose that this drug be considered as a candidate drug
      for the prevention of AD. 

PMID- 24098474
TI  - Microdeletion and microduplication analysis of chinese conotruncal defects
      patients with targeted array comparative genomic hybridization.
AB  - OBJECTIVE: The current study aimed to develop a reliable targeted array
      comparative genomic hybridization (aCGH) to detect microdeletions and
      microduplications in congenital conotruncal defects (CTDs), especially on 22q11.2
      region, and for some other chromosomal aberrations, such as 5p15-5p, 7q11.23 and
      4p16.3. METHODS: Twenty-seven patients with CTDs, including 12 pulmonary atresia
      (PA), 10 double-outlet right ventricle (DORV), 3 transposition of great arteries
      (TGA), 1 tetralogy of Fallot (TOF) and one ventricular septal defect (VSD), were
      enrolled in this study and screened for pathogenic copy number variations (CNVs),
      using Agilent 8 x 15K targeted aCGH. Real-time quantitative polymerase chain
      reaction (qPCR) was performed to test the molecular results of targeted aCGH.
      RESULTS: Four of 27 patients (14.8%) had 22q11.2 CNVs, 1 microdeletion and 3
      microduplications. qPCR test confirmed the microdeletion and microduplication
      detected by the targeted aCGH. CONCLUSION: Chromosomal abnormalities were a well
      known cause of multiple congenital anomalies (MCA). This aCGH using arrays with
      high-density coverage in the targeted regions can detect genomic imbalances
      including 22q11.2 and other 10 kinds CNVs effectively and quickly. This approach
      has the potential to be applied to detect aneuploidy and common
      microdeletion/microduplication syndromes on a single microarray.

PMID- 24098475
TI  - Medication possession ratio predicts antiretroviral regimens persistence in Peru.
AB  - OBJECTIVES: In developing nations, the use of operational parameters (OPs) in the
      prediction of clinical care represents a missed opportunity to enhance the care
      process. We modeled the impact of multiple measurements of antiretroviral
      treatment (ART) adherence on antiretroviral treatment outcomes in Peru. DESIGN
      AND METHODS: Retrospective cohort study including ART naive, non-pregnant, adults
      initiating therapy at Hospital Nacional Cayetano Heredia, Lima-Peru (2006-2010).
      Three OPs were defined: 1) Medication possession ratio (MPR): days with
      antiretrovirals dispensed/days on first-line therapy; 2) Laboratory monitory
      constancy (LMC): proportion of 6 months intervals with >=1 viral load or CD4
      reported; 3) Clinic visit constancy (CVC): proportion of 6 months intervals with
      >=1 clinic visit. Three multi-variable Cox proportional hazard (PH) models (one
      per OP) were fit for (1) time of first-line ART persistence and (2) time to
      second-line virologic failure. All models were adjusted for socio-demographic,
      clinical and laboratory variables. RESULTS: 856 patients were included in first
      line persistence analyses, median age was 35.6 years [29.4-42.9] and most were
      male (624; 73%). In multivariable PH models, MPR (per 10% increase HR=0.66;
      95%CI=0.61-0.71) and LMC (per 10% increase 0.83; 0.71-0.96) were associated with
      prolonged time on first-line therapies. Among 79 individuals included in time to
      second-line virologic failure analyses, MPR was the only OP independently
      associated with prolonged time to second-line virologic failure (per 10% increase
      0.88; 0.77-0.99). CONCLUSIONS: The capture and utilization of program level
      parameters such as MPR can provide valuable insight into patient-level treatment
      outcomes.

PMID- 24098476
TI  - CEP biomarkers as potential tools for monitoring therapeutics.
AB  - BACKGROUND: Carboxyethylpyrrole (CEP) adducts are oxidative modifications derived
      from docosahexaenoate-containing lipids that are elevated in ocular tissues and
      plasma in age-related macular degeneration (AMD) and in rodents exposed to
      intense light. The goal of this study was to determine whether light-induced CEP
      adducts and autoantibodies are modulated by pretreatment with AL-8309A under
      conditions that prevent photo-oxidative damage of rat retina. AL-8309A is a
      serotonin 5-HT1A receptor agonist. METHODS: Albino rats were dark adapted prior
      to blue light exposure. Control rats were maintained in normal cyclic light. Rats
      were injected subcutaneously 3x with 10 mg/kg AL-8309A (2 days, 1 day and 0
      hours) before light exposure for 6 h (3.1 mW/cm(2), lambda=450 nm). Animals were
      sacrificed immediately following light exposure and eyes, retinas and plasma were
      collected. CEP adducts and autoantibodies were quantified by Western analysis or
      ELISA. RESULTS: ANOVA supported significant differences in mean amounts of CEP
      adducts and autoantibodies among the light + vehicle, light + drug and dark
      control groups from both retina and plasma. Light-induced CEP adducts in retina
      were reduced ~20% following pretreatment with AL-8309A (n = 62 rats, p = 0.006)
      and retinal CEP immunoreactivity was less intense by immunohistochemistry. Plasma
      levels of light-induced CEP adducts were reduced at least 30% (n = 15 rats, p =
      0.004) by drug pretreatment. Following drug treatment, average CEP autoantibody
      titer in light exposed rats (n = 22) was unchanged from dark control levels, and
      ~20% (p = 0.046) lower than in vehicle-treated rats. CONCLUSIONS: Light-induced
      CEP adducts in rat retina and plasma were significantly decreased by pretreatment
      with AL-8309A. These results are consistent with and extend previous studies
      showing AL-8309A reduces light-induced retinal lesions in rats and support CEP
      biomarkers as possible tools for monitoring the efficacy of select therapeutics.

PMID- 24098477
TI  - Extracellular alkaline pH leads to increased metastatic potential of estrogen
      receptor silenced endocrine resistant breast cancer cells.
AB  - INTRODUCTION: Endocrine resistance in breast cancer is associated with enhanced
      metastatic potential and poor clinical outcome, presenting a significant
      therapeutic challenge. We have established several endocrine insensitive breast
      cancer lines by shRNA induced depletion of estrogen receptor (ER) by transfection
      of MCF-7 cells which all exhibit enhanced expression profile of mesenchymal
      markers with reduction of epithelial markers, indicating an epithelial to
      mesenchymal transition. In this study we describe their behaviour in response to
      change in extracellular pH, an important factor controlling cell motility and
      metastasis. METHODS: Morphological changes associated with cell exposure to
      extracellular alkaline pH were assessed by live cell microscopy and the effect of
      various ion pumps on this behavior was investigated by pretreatment with chemical
      inhibitors. The activity and expression profile of key signaling molecules was
      assessed by western blotting. Cell motility and invasion were examined by scratch
      and under-agarose assays respectively. Total matrix metalloproteinase (MMP)
      activity and specifically of MMP2/9 was assessed in conditioned medium in
      response to brief alkaline pH exposure. RESULTS: Exposure of ER -ve but not ER
      +ve breast cancer cells to extracellular alkaline pH resulted in cell shrinkage
      and spherical appearance (termed contractolation); this was reversed by returning
      the pH back to 7.4. Contractolation was blocked by targeting the Na(+)/K(+) and
      Na(+)/H(+) pumps with specific chemical inhibitors. The activity and expression
      profile of key signaling molecules critical for cell adhesion were modulated by
      the exposure to alkaline pH. Brief exposure to alkaline pH enhanced MMP2/9
      activity and the invasive potential of ER -ve cells in response to serum
      components and epithelial growth factor stimulation without affecting unhindered
      motility. CONCLUSIONS: Endocrine resistant breast cancer cells behave very
      differently to estrogen responsive cells in alkaline pH, with enhanced invasive
      potential; these studies emphasise the crucial influence of extracellular pH and
      caution against indiscriminate application of alkalinising drug therapy.

PMID- 24098478
TI  - Psychometrics properties of early trauma inventory self report - short form
      (ETISR-SR) for the Brazilian context.
AB  - This study aims to translate and validate Early Trauma Inventory Self Report 
      Short Form (ETISR-SF) to Brazilian Portuguese. 253 adult subjects answered the
      ETISR-SF, Beck Anxiety Inventory (BAI), Fagerstrom Test for Nicotine Dependence
      (FTND), Patient Health Questionnaire (PHQ-9) and Fast Alcohol Screening Test
      (FAST). The instrument showed good internal consistency (0.83). Correlations with
      the PHQ-9 and BAI were moderate (r=0.26-0.47) and showed the expected
      associations with psychiatric constructs. No associations were found for FTND and
      FAST. Confirmatory Factor Analysis revealed that a correlated four-factor model
      as well as a second order model subsuming four lower order components presented
      the best model fit. Test-retest reliability was also excellent (ICC=0.78-0.90).
      ETISR-SF is suitable for assessing traumatic experiences in a Brazilian community
      sample. Given the importance of trauma as a public health problem, tools such as
      ETISR-SF may help clinicians/ researchers to better evaluate and measure such
      events and further advance clinical care of trauma victims. 

PMID- 24098479
TI  - TGF-beta1 downregulates COX-2 expression leading to decrease of PGE2 production
      in human lung cancer A549 cells, which is involved in fibrotic response to TGF
      beta1.
AB  - Transforming growth factor-beta1 (TGF-beta1) is a multifunctional cytokine that
      is involved in various pathophysiological processes, including cancer progression
      and fibrotic disorders. Here, we show that treatment with TGF-beta1 (5 ng/mL)
      induced downregulation of cyclooxygenase-2 (COX-2), leading to reduced synthesis
      of prostaglandin E2 (PGE2), in human lung cancer A549 cells. Treatment of cells
      with specific inhibitors of COX-2 or PGE2 receptor resulted in growth inhibition,
      indicating that the COX-2/PGE2 pathway contributes to proliferation in an
      autocrine manner. TGF-beta1 treatment induced growth inhibition, which was
      attenuated by exogenous PGE2. TGF-beta1 is also a potent inducer of epithelial
      mesenchymal transition (EMT), a phenotype change in which epithelial cells
      differentiate into fibroblastoid cells. Supplementation with PGE2 or PGE2
      receptor EP4 agonist PGE1-alcohol, as compared with EP1/3 agonist sulprostone,
      inhibited TGF-beta1-induced expression of fibronectin and collagen I
      (extracellular matrix components). Exogenous PGE2 or PGE2 receptor agonists also
      suppressed actin remodeling induced by TGF-beta1. These results suggest that PGE2
      has an anti-fibrotic effect. We conclude that TGF-beta1-induced downregulation of
      COX-2/PGE2 signaling is involved in facilitation of fibrotic EMT response in A549
      cells. 

PMID- 24098480
TI  - Oligomerization interface of RAGE receptor revealed by MS-monitored hydrogen
      deuterium exchange.
AB  - Activation of the receptor for advanced glycation end products (RAGE) leads to a
      chronic proinflammatory signal, affecting patients with a variety of diseases.
      Potentially beneficial modification of RAGE activity requires understanding the
      signal transduction mechanism at the molecular level. The ligand binding domain
      is structurally uncoupled from the cytoplasmic domain, suggesting receptor
      oligomerization is a requirement for receptor activation. In this study, we used
      hydrogen-deuterium exchange and mass spectrometry to map structural differences
      between the monomeric and oligomeric forms of RAGE. Our results indicated the
      presence of a region shielded from exchange in the oligomeric form of RAGE and
      led to the identification of a new oligomerization interface localized at the
      linker region between domains C1 and C2. Based on this finding, a model of a RAGE
      dimer and higher oligomeric state was constructed. 

PMID- 24098482
TI  - Gender differences: examination of the 12-item bem sex role inventory (BSRI-12)
      in an older Brazilian population.
AB  - OBJECTIVES: Although gender is often acknowledged as a determinant of health,
      measuring its components, other than biological sex, is uncommon. The Bem Sex
      Role Inventory (BSRI) quantifies self-attribution of traits, indicative of gender
      roles. The BSRI has been used with participants across cultures and countries,
      but rarely in an older population in Brazil, as we have done in this study. Our
      primary objective was to determine whether the BSRI-12 can be used to explore
      gender in an older Brazilian population. METHODS: The BSRI was completed by
      volunteer participants, all community dwelling adults aged 65+ living in Natal,
      Brazil. Exploratory factor analysis was performed, followed by a varimax rotation
      (orthogonal solution) for iteration to examine the underlying gender roles of
      feminine, masculine, androgynous and undifferentiated, and to validate the BSRI
      in older adults in Brazil. RESULTS: The 278 participants, (80 men, 198 women)
      were 65-99 years old (average 73.6 for men, 74.7 for women). Age difference
      between sexes was not significant (p = 0.22). A 12 item version of the BSRI (BSRI
      12) previously validated among Spanish seniors was used and showed validity with
      5 BSRI-12 items (Cronbach=0.66) loading as feminine, 6 items (Cronbach=0.51)
      loading onto masculine roles and neither overlapping with the category of
      biological sex of respondent. CONCLUSIONS: Although the BSRI-12 appears to be a
      valid indicator of gender among elderly Brazilians, the gender role status
      identified with the BSRI-12 was not correlated with being male or female.

PMID- 24098481
TI  - Crystal structure of the human short coiled coil protein and insights into SCOC
      FEZ1 complex formation.
AB  - The short coiled coil protein (SCOC) forms a complex with fasciculation and
      elongation protein zeta 1 (FEZ1). This complex is involved in autophagy
      regulation. We determined the crystal structure of the coiled coil domain of
      human SCOC at 2.7 A resolution. SCOC forms a parallel left handed coiled coil
      dimer. We observed two distinct dimers in the crystal structure, which shows that
      SCOC is conformationally flexible. This plasticity is due to the high incidence
      of polar and charged residues at the core a/d-heptad positions. We prepared two
      double mutants, where these core residues were mutated to either leucines or
      valines (E93V/K97L and N125L/N132V). These mutations led to a dramatic increase
      in stability and change of oligomerisation state. The oligomerisation state of
      the mutants was characterized by multi-angle laser light scattering and native
      mass spectrometry measurements. The E93V/K97 mutant forms a trimer and the
      N125L/N132V mutant is a tetramer. We further demonstrate that SCOC forms a stable
      homogeneous complex with the coiled coil domain of FEZ1. SCOC dimerization and
      the SCOC surface residue R117 are important for this interaction. 

PMID- 24098483
TI  - N-acetyl-L-cysteine prevents stress-induced desmin aggregation in cellular models
      of desminopathy.
AB  - Mutations within the human desmin gene are responsible for a subcategory of
      myofibrillar myopathies called desminopathies. However, a single inherited
      mutation can produce different phenotypes within a family, suggesting that
      environmental factors influence disease states. Although several mouse models
      have been used to investigate organ-specific desminopathies, a more general
      mechanistic perspective is required to advance our knowledge toward patient
      treatment. To improve our understanding of disease pathology, we have developed
      cellular models to observe desmin behaviour in early stages of disease pathology,
      e.g., upon formation of cytoplasmic desmin aggregates, within an isogenic
      background. We cloned the wildtype and three mutant desmin cDNAs using a Tet-On
      Advanced(r) expression system in C2C12 cells. Mutations were selected based on
      positioning within desmin and capacity to form aggregates in transient
      experiments, as follows: DesS46Y (head domain; low aggregation), DesD399Y
      (central rod domain; high aggregation), and DesS460I (tail domain; moderate
      aggregation). Introduction of these proteins into a C2C12 background permitted us
      to compare between desmin variants as well as to determine the role of external
      stress on aggregation. Three different types of stress, likely encountered during
      muscle activity, were introduced to the cell models-thermal (heat shock), redox
      associated (H2O2 and cadmium chloride), and mechanical (stretching) stresses
      after which aggregation was measured. Cells containing variant DesD399Y were more
      sensitive to stress, leading to marked cytoplasmic perinuclear aggregations. We
      then evaluated the capacity of biochemical compounds to prevent this aggregation,
      applying dexamethasone (an inducer of heat shock proteins), fisetin or N-acetyl-L
      cysteine (antioxidants) before stress induction. Interestingly, N-acetyl-L
      cysteine pre-treatment prevented DesD399Y aggregation during most stress. N
      acetyl-L-cysteine has recently been described as a promising antioxidant in
      myopathies linked to selenoprotein N or ryanodin receptor defects. Our findings
      indicate that this drug warrants further study in animal models to speed its
      potential development as a therapy for DesD399Y-linked desminopathies. 

PMID- 24098484
TI  - NMDA and PACAP receptor signaling interact to mediate retinal-induced scn
      cellular rhythmicity in the absence of light.
AB  - The "core" region of the suprachiasmatic nucleus (SCN), a central clock
      responsible for coordinating circadian rhythms, shows a daily rhythm in
      phosphorylation of extracellular regulated kinase (pERK). This cellular rhythm
      persists under constant darkness and, despite the absence of light, is dependent
      upon inputs from the eye. The neural signals driving this rhythmicity remain
      unknown and here the roles of glutamate and PACAP are examined. First, rhythmic
      phosphorylation of the NR1 NMDA receptor subunit (pNR1, a marker for receptor
      activation) was shown to coincide with SCN core pERK, with a peak at circadian
      time (CT) 16. Enucleation and intraocular TTX administration attenuated the peak
      in the pERK and pNR1 rhythms, demonstrating that activation of the NMDA receptor
      and ERK in the SCN core at CT16 are dependent on retinal inputs. In contrast, ERK
      and NR1 phosphorylation in the SCN shell region were unaffected by these
      treatments. Intraventricular administration of the NMDA receptor antagonist MK
      801 also attenuated the peak in SCN core pERK, indicating that ERK
      phosphorylation in this region requires NMDA receptor activation. As PACAP is
      implicated in photic entrainment and is known to modulate glutamate signaling,
      the effects of a PAC1 receptor antagonist (PACAP 6-38) on SCN core pERK and pNR1
      also were examined. PACAP 6-38 administration attenuated SCN core pERK and pNR1,
      suggesting that PACAP induces pERK directly, and indirectly via a modulation of
      NMDA receptor signaling. Together, these data indicate that, in the absence of
      light, retinal-mediated NMDA and PAC1 receptor activation interact to induce
      cellular rhythms in the SCN core. These results highlight a novel function for
      glutamate and PACAP release in the hamster SCN apart from their well-known roles
      in the induction of photic circadian clock resetting. 

PMID- 24098485
TI  - REEPs are membrane shaping adapter proteins that modulate specific g protein
      coupled receptor trafficking by affecting ER cargo capacity.
AB  - Receptor expression enhancing proteins (REEPs) were identified by their ability
      to enhance cell surface expression of a subset of G protein-coupled receptors
      (GPCRs), specifically GPCRs that have proven difficult to express in heterologous
      cell systems. Further analysis revealed that they belong to the Yip (Ypt
      interacting protein) family and that some REEP subtypes affect ER structure. Yip
      family comparisons have established other potential roles for REEPs, including
      regulation of ER-Golgi transport and processing/neuronal localization of cargo
      proteins. However, these other potential REEP functions and the mechanism by
      which they selectively enhance GPCR cell surface expression have not been
      clarified. By utilizing several REEP family members (REEP1, REEP2, and REEP6) and
      model GPCRs (alpha2A and alpha2C adrenergic receptors), we examined REEP
      regulation of GPCR plasma membrane expression, intracellular processing, and
      trafficking. Using a combination of immunolocalization and biochemical methods,
      we demonstrated that this REEP subset is localized primarily to ER, but not
      plasma membranes. Single cell analysis demonstrated that these REEPs do not
      specifically enhance surface expression of all GPCRs, but affect ER cargo
      capacity of specific GPCRs and thus their surface expression. REEP co-expression
      with alpha2 adrenergic receptors (ARs) revealed that this REEP subset interacts
      with and alter glycosidic processing of alpha2C, but not alpha2A ARs,
      demonstrating selective interaction with cargo proteins. Specifically, these
      REEPs enhanced expression of and interacted with minimally/non-glycosylated forms
      of alpha2C ARs. Most importantly, expression of a mutant REEP1 allele (hereditary
      spastic paraplegia SPG31) lacking the carboxyl terminus led to loss of this
      interaction. Thus specific REEP isoforms have additional intracellular functions
      besides altering ER structure, such as enhancing ER cargo capacity, regulating ER
      Golgi processing, and interacting with select cargo proteins. Therefore, some
      REEPs can be further described as ER membrane shaping adapter proteins. 

PMID- 24098486
TI  - Characterization of T cell receptors of Th1 cells infiltrating inflamed skin of a
      novel murine model of palladium-induced metal allergy.
AB  - Metal allergy is categorized as a delayed-type hypersensitivity reaction, and is
      characterized by the recruitment of lymphocytes into sites of allergic
      inflammation. Because of the unavailability of suitable animal models for metal
      allergy, the role of T cells in the pathogenesis of metal allergy has not been
      explored. Thus, we developed a novel mouse model for metal allergy associated
      with infiltration of T cells by multiple injections of palladium (Pd) plus
      lipopolysaccharide into the footpad. Using this model, we characterized footpad
      infiltrating T cells in terms of phenotypic markers, T cell receptor (TCR)
      repertoires and cytokine expression. CD3+ CD4+ T cells accumulated in the
      allergic footpads 7 days after Pd challenge. The expression levels of CD25,
      interleukin-2, interferon-gamma and tumor necrosis factor, but not interleukin-4
      and interleukin-5, increased in the footpads after challenge, suggesting CD4+ T
      helper 1 (Th1) cells locally expanded in response to Pd. Infiltrated T cells in
      the footpads frequently expressed AV18-1 and BV8-2 T cell receptor (TCR) chains
      compared with T cells in the lymph nodes and exhibited oligoclonality. T-cell
      clones identified from Pd-allergic mouse footpads shared identical CDR3 sequences
      containing AV18-1 and BV8-2. These results suggest that TCR AV18-1 and BV8-2 play
      dominant and critical parts in the antigen specificity of Pd-specific Th1 cells. 

PMID- 24098487
TI  - Mutations in non-acid patch residues disrupt H2A.Z's association with chromatin
      through multiple mechanisms.
AB  - The incorporation of histone variants into nucleosomes is a critical mechanism
      for regulating essential DNA-templated processes and for establishing distinct
      chromatin architectures with specialised functions. H2A.Z is an evolutionarily
      conserved H2A variant that has diverse roles in transcriptional regulation,
      heterochromatin boundary definition, chromosome stability and DNA repair. The
      H2A.Z C-terminus diverges in sequence from canonical H2A and imparts unique
      functions to H2A.Z in the yeast S. cerevisiae. Although mediated in part through
      the acid patch-containing M6 region, many molecular determinants of this
      divergent structure-function relationship remain unclear. Here, by using an
      unbiased random mutagenesis screen of H2A.Z alleles, we identify point mutations
      in the C-terminus outside of the M6 region that disrupt the normal function of
      H2A.Z in response to cytotoxic stress. These functional defects correlate with
      reduced chromatin association, which we attribute to reduced physical stability
      within chromatin, but also to altered interactions with the SWR and INO80
      chromatin remodeling complexes. Together with experimental data, computational
      modelling of these residue changes in the context of protein structure suggests
      the importance of C-terminal domain integrity and configuration for maintaining
      the level of H2A.Z in nucleosomes. 

PMID- 24098488
TI  - Discovery and confirmation of O-GlcNAcylated proteins in rat liver mitochondria
      by combination of mass spectrometry and immunological methods.
AB  - O-linked beta-N-acetylglucosamine (O-GlcNAc) is an important post-translational
      modification (PTM) consisting of a single N-acetylglucosamine moiety attached via
      an O-beta-glycosidic linkage to serine and threonine residues. Glycosylation with
      O-GlcNAc occurs on myriad nuclear and cytosolic proteins from almost all
      functional classes. However, with respect to O-GlcNAcylated proteins special in
      mitochondria, little attention has been paid. In this study, we combined mass
      spectrometry and immunological methods to perform global exploration of O
      GlcNAcylated proteins specific in mitochondria of rat liver. First, highly
      purified mitochondrial proteins were obviously shown to be O-GlcNAcylated by
      immunoblot profiling. Then, beta-elimination followed by Michael Addition with
      Dithiothreitol (BEMAD) treatment and LC-MS/MS were performed to enrich and
      identify O-GlcNAcylated mitochondrial proteins, resulting in an unambiguous
      assignment of 14 O-GlcNAcylation sites, mapping to 11 O-GlcNAcylated proteins.
      Furthermore, the identified O-GlcNAcylated mitochondrial proteins were fully
      validated by both electron transfer dissociation tandem mass spectrometry
      (ETD/MS/MS) and western blot. Thus, for the first time, our study definitely not
      only identified but also validated that some mitochondrial proteins in rat liver
      are O-GlcNAcylated. Interestingly, all of these O-GlcNAcylated mitochondrial
      proteins are enzymes, the majority of which are involved in a wide variety of
      biological processes, such as urea cycle, tricarboxylic acid cycle and lipid
      metabolism, indicating a role for protein O-GlcNAcylation in mitochondrial
      function. 

PMID- 24098489
TI  - Simultaneous identification and quantification of 20 beta-receptor agonists in
      feed using gas chromatography-tandem mass spectrometry.
AB  - "Lean meat powder" is a class of toxic chemicals that have structures similar to
      that of beta-adrenergic receptor agonists. At least 16 chemicals from this class
      have been specifically banned by the 176(th) bulletin of the Chinese Department
      of Agriculture on breeding animals, and methods for monitoring the illicit use of
      beta-agonists in animal feed are required. Herein, a method to quantify 20 beta
      agonists in feed, via analyte derivatization followed by gas chromatography
      tandem mass spectrometry, has been developed. The optimized method has a good
      linear correlation (calibration coefficient > 0.99) between the quantitative ion
      peak area and the concentration of beta-agonists over a large working range (0.05
      1 mg/kg). The limit of detection (LOD) was 0.01 mg/kg, the recoveries for three
      beta-agonists spikes (0.05, 0.1, and 1 ug/g) in feed ranged from 75.6 to 102.4%,
      repeatability ranged from 1.2 to 9.4% for all of the compounds, and intermediate
      precisions were lower than 13.8%. This precise, accurate method was applied to
      quantify 20 beta-agonists in actual feed samples and represents an excellent
      complement to existing quantification methods. 

PMID- 24098490
TI  - Tumor suppressive function of mir-205 in breast cancer is linked to HMGB3
      regulation.
AB  - Identifying targets of dysregulated microRNAs (miRNAs) will enhance our
      understanding of how altered miRNA expression contributes to the malignant
      phenotype of breast cancer. The expression of miR-205 was reduced in four breast
      cancer cell lines compared to the normal-like epithelial cell line MCF10A and in
      tumor and metastatic tissues compared to adjacent benign breast tissue. Two
      predicted binding sites for miR-205 were identified in the 3' untranslated region
      of the high mobility group box 3 gene, HMGB3. Both dual-luciferase reporter assay
      and Western blotting confirmed that miR-205 binds to and regulates HMGB3. To
      further explore miR-205 targeting of HMGB3, WST-1 proliferation and in vitro
      invasion assays were performed in MDA-MB-231 and BT549 cells transiently
      transfected with precursor miR-205 oligonucleotide or HMGB3 small interfering RNA
      (siRNA). Both treatments reduced the proliferation and invasion of the cancer
      cells. The mRNA and protein levels of HMGB3 were higher in the tumor compared to
      adjacent benign specimens and there was an indirect correlation between the
      expression of HMGB3 mRNA and patient survival. Treatment of breast cancer cells
      with 5-Aza/TSA derepressed miR-205 and reduced HMGB3 mRNA while knockdown of the
      transcriptional repressor NRSF/REST, reduced miR-205 and increased HMGB3. In
      conclusion, regulation of HMGB3 by miR-205 reduced both proliferation and
      invasion of breast cancer cells. Our findings suggest that modulating miR-205
      and/or targeting HMGB3 are potential therapies for advanced breast cancer. 

PMID- 24098491
TI  - Purine nucleoside phosphorylase targeted by annexin v to breast cancer
      vasculature for enzyme prodrug therapy.
AB  - BACKGROUND AND PURPOSE: The targeting of therapeutics is a promising approach for
      the development of new cancer treatments that seek to reduce the devastating side
      effects caused by the systemic administration of current drugs. This study
      evaluates a fusion protein developed as an enzyme prodrug therapy targeted to the
      tumor vasculature. Cytotoxicity would be localized to the site of the tumor using
      a protein fusion of purine nucleoside phosphorylase (PNP) and annexin V. Annexin
      V acts as the tumor-targeting component of the fusion protein as it has been
      shown to bind to phosphatidylserine expressed externally on cancer cells and the
      endothelial cells of the tumor vasculature, but not normal vascular endothelial
      cells. The enzymatic component of the fusion, PNP, converts the FDA-approved
      cancer therapeutic, fludarabine, into a more cytotoxic form. The purpose of this
      study is to determine if this system has a good potential as a targeted therapy
      for breast cancer. METHODS: A fusion of E. coli purine nucleoside phosphorylase
      and human annexin V was produced in E. coli and purified. Using human breast
      cancer cell lines MCF-7 and MDA-MB-231 and non-confluent human endothelial cells
      grown in vitro, the binding strength of the fusion protein and the cytotoxicity
      of the enzyme prodrug system were determined. Endothelial cells that are not
      confluent expose phosphatidylserine and therefore mimic the tumor vasculature.
      RESULTS: The purified recombinant fusion protein had good enzymatic activity and
      strong binding to the three cell lines. There was significant cell killing
      (p<0.001) by the enzyme prodrug treatment for all three cell lines, with greater
      than 80% cytotoxicity obtained after 6 days of treatment. CONCLUSION: These
      results suggest that this treatment could be useful as a targeted therapy for
      breast cancer.

PMID- 24098492
TI  - Regulation of mammalian autophagy by class II and III PI 3-kinases through PI3P
      synthesis.
AB  - Synthesis of phosphatidylinositol-3-phosphate (PI3P) by Vps34, a class III
      phosphatidylinositol 3-kinase (PI3K), is critical for the initial steps of
      autophagosome (AP) biogenesis. Although Vps34 is the sole source of PI3P in
      budding yeast, mammalian cells can produce PI3P through alternate pathways,
      including direct synthesis by the class II PI3Ks; however, the physiological
      relevance of these alternate pathways in the context of autophagy is unknown.
      Here we generated Vps34 knockout mouse embryonic fibroblasts (MEFs) and using a
      higher affinity 4x-FYVE finger PI3P-binding probe found a Vps34-independent pool
      of PI3P accounting for (~)35% of the total amount of this lipid species by
      biochemical analysis. Importantly, WIPI-1, an autophagy-relevant PI3P probe,
      still formed some puncta upon starvation-induced autophagy in Vps34 knockout
      MEFs. Additional characterization of autophagy by electron microscopy as well as
      protein degradation assays showed that while Vps34 is important for starvation
      induced autophagy there is a significant component of functional autophagy
      occurring in the absence of Vps34. Given these findings, class II PI3Ks (alpha
      and beta isoforms) were examined as potential positive regulators of autophagy.
      Depletion of class II PI3Ks reduced recruitment of WIPI-1 and LC3 to AP
      nucleation sites and caused an accumulation of the autophagy substrate, p62,
      which was exacerbated upon the concomitant ablation of Vps34. Our studies
      indicate that while Vps34 is the main PI3P source during autophagy, class II
      PI3Ks also significantly contribute to PI3P generation and regulate AP
      biogenesis. 

PMID- 24098494
TI  - Importance of native grassland habitat for den-site selection of Indian foxes in
      a fragmented landscape.
AB  - Fragmentation of native habitats is now a ubiquitous phenomenon affecting
      wildlife at various scales. We examined selection of den-sites (n = 26) by Indian
      foxes (Vulpes bengalensis) in a highly modified short-grassland landscape in
      central India (Jan-May, 2010). At the scale of the home-range, defined by an 800
      m circular buffer around den sites, we examined the effect of land-cover edges
      and roads on selection of sites for denning using a distance-based approach. At
      the smaller den-area scale, defined by a 25 m x 25 m plot around den and paired
      available sites, the effect of microhabitat characteristics was examined using
      discrete-choice models. Indian foxes selected den-sites closer to native
      grasslands (t = -9.57, P < 0.001) and roads (t = -2.04, P = 0.05) than random at
      the home-range scale. At the smaller scale, abundance of rodents and higher
      visibility increased the odds of selection of a site by eight and four times
      respectively, indicating resource availability and predator avoidance to be
      important considerations for foxes. Indian foxes largely chose to den in human
      made structures, indicated by the proportion of dens found in earthen bunds
      (0.69) and boulder piles (0.27) in the study area. With agricultural expansion
      and human modification threatening native short-grassland habitats, their
      conservation and effective management in human-dominated landscapes will benefit
      the Indian fox. The presence of some human-made structures within native
      grasslands would also be beneficial for this den-dependent species. We suggest
      future studies examine the impact of fragmentation and connectivity of grasslands
      on survival and reproductive success of the Indian fox. 

PMID- 24098493
TI  - A novel DNA vaccine technology conveying protection against a lethal herpes
      simplex viral challenge in mice.
AB  - While there are a number of licensed veterinary DNA vaccines, to date, none have
      been licensed for use in humans. Here, we demonstrate that a novel technology
      designed to enhance the immunogenicity of DNA vaccines protects against lethal
      herpes simplex virus 2 (HSV-2) challenge in a murine model. Polynucleotides were
      modified by use of a codon optimization algorithm designed to enhance immune
      responses, and the addition of an ubiquitin-encoding sequence to target the
      antigen to the proteasome for processing and to enhance cytotoxic T cell
      responses. We show that a mixture of these codon-optimized ubiquitinated and non
      ubiquitinated constructs encoding the same viral envelope protein, glycoprotein
      D, induced both B and T cell responses, and could protect against lethal viral
      challenge and reduce ganglionic latency. The optimized vaccines, subcloned into a
      vector suitable for use in humans, also provided a high level of protection
      against the establishment of ganglionic latency, an important correlate of HSV
      reactivation and candidate endpoint for vaccines to proceed to clinical trials. 

PMID- 24098495
TI  - Karyopherin alpha2 is essential for rRNA transcription and protein synthesis in
      proliferative keratinocytes.
AB  - Karyopherin proteins mediate nucleocytoplasmic trafficking and are critical for
      protein and RNA subcellular localization. Recent studies suggest KPNA2 expression
      is induced in tumor cells and is strongly associated with prognosis, although the
      precise roles and mechanisms of KPNA2 overexpression in proliferative disorders
      have not been defined. We found that KPNA2 expression is induced in various
      proliferative disorders of the skin such as psoriasis, Bowen's disease, actinic
      keratosis, squamous cell carcinoma, Paget's disease, Merkel cell carcinoma, and
      mycosis fungoides. siRNA-mediated KPNA suppression revealed that KPNA2 is
      essential for significant suppression of HaCaT proliferation under starvation
      conditions. Ribosomal RNA transcription and protein synthesis were suppressed by
      starvation combined with knockdown of KPNA (including KPNA2) expression. KPNA2
      localized to the nucleolus and interacted with proteins associated with mRNA
      processing, ribonucleoprotein complex biogenesis, chromatin modification, and
      transcription, as demonstrated by tandem affinity purification and mass
      spectrometry. KPNA2 may be an important promoter of ribosomal RNA and protein
      synthesis in tumor cells. 

PMID- 24098496
TI  - Leptospira interrogans serovar copenhageni harbors two lexA genes involved in SOS
      response.
AB  - Bacteria activate a regulatory network in response to the challenges imposed by
      DNA damage to genetic material, known as the SOS response. This system is
      regulated by the RecA recombinase and by the transcriptional repressor lexA.
      Leptospira interrogans is a pathogen capable of surviving in the environment for
      weeks, being exposed to a great variety of stress agents and yet retaining its
      ability to infect the host. This study aims to investigate the behavior of L.
      interrogans serovar Copenhageni after the stress induced by DNA damage. We show
      that L. interrogans serovar Copenhageni genome contains two genes encoding
      putative LexA proteins (lexA1 and lexA2) one of them being potentially acquired
      by lateral gene transfer. Both genes are induced after DNA damage, but the steady
      state levels of both LexA proteins drop, probably due to auto-proteolytic
      activity triggered in this condition. In addition, seven other genes were up
      regulated following UV-C irradiation, recA, recN, dinP, and four genes encoding
      hypothetical proteins. This set of genes is potentially regulated by LexA1, as it
      showed binding to their promoter regions. All these regions contain degenerated
      sequences in relation to the previously described SOS box, TTTGN 5CAAA. On the
      other hand, LexA2 was able to bind to the palindrome TTGTAN10TACAA, found in its
      own promoter region, but not in the others. Therefore, the L. interrogans serovar
      Copenhageni SOS regulon may be even more complex, as a result of LexA1 and LexA2
      binding to divergent motifs. New possibilities for DNA damage response in
      Leptospira are expected, with potential influence in other biological responses
      such as virulence. 

PMID- 24098497
TI  - Concurrent gene signatures for han chinese breast cancers.
AB  - The interplay between copy number variation (CNV) and differential gene
      expression may be able to shed light on molecular process underlying breast
      cancer and lead to the discovery of cancer-related genes. In the current study,
      genes concurrently identified in array comparative genomic hybridization (CGH)
      and gene expression microarrays were used to derive gene signatures for Han
      Chinese breast cancers. We performed 23 array CGHs and 81 gene expression
      microarrays in breast cancer samples from Taiwanese women. Genes with coherent
      patterns of both CNV and differential gene expression were identified from the 21
      samples assayed using both platforms. We used these genes to derive signatures
      associated with clinical ER and HER2 status and disease-free survival.
      DISTRIBUTIONS OF SIGNATURE GENES WERE STRONGLY ASSOCIATED WITH CHROMOSOMAL
      LOCATION: chromosome 16 for ER and 17 for HER2. A breast cancer risk predictive
      model was built based on the first supervised principal component from 16 genes
      (RCAN3, MCOLN2, DENND2D, RWDD3, ZMYM6, CAPZA1, GPR18, WARS2, TRIM45, SCRN1,
      CSNK1E, HBXIP, CSDE1, MRPL20, IKZF1, and COL20A1), and distinct survival patterns
      were observed between the high- and low-risk groups from the combined dataset of
      408 microarrays. The risk score was significantly higher in breast cancer
      patients with recurrence, metastasis, or mortality than in relapse-free
      individuals (0.241 versus 0, P<0.001). The concurrent gene risk predictive model
      remained discriminative across distinct clinical ER and HER2 statuses in subgroup
      analysis. Prognostic comparisons with published gene expression signatures showed
      a better discerning ability of concurrent genes, many of which were rarely
      identifiable if expression data were pre-selected by phenotype correlations or
      variability of individual genes. We conclude that parallel analysis of CGH and
      microarray data, in conjunction with known gene expression patterns, can be used
      to identify biomarkers with prognostic values in breast cancer. 

PMID- 24098498
TI  - The choice of PCR primers has great impact on assessments of bacterial community
      diversity and dynamics in a wastewater treatment plant.
AB  - Assessments of bacterial community diversity and dynamics are fundamental for the
      understanding of microbial ecology as well as biotechnological applications. We
      show that the choice of PCR primers has great impact on the results of analyses
      of diversity and dynamics using gene libraries and DNA fingerprinting. Two
      universal primer pairs targeting the 16S rRNA gene, 27F&1492R and 63F&M1387R,
      were compared and evaluated by analyzing the bacterial community in the activated
      sludge of a large-scale wastewater treatment plant. The two primer pairs targeted
      distinct parts of the bacterial community, none encompassing the other, both with
      similar richness. Had only one primer pair been used, very different conclusions
      had been drawn regarding dominant phylogenetic and putative functional groups.
      With 27F&1492R, Betaproteobacteria would have been determined to be the
      dominating taxa while 63F&M1387R would have described Alphaproteobacteria as the
      most common taxa. Microscopy and fluorescence in situ hybridization analysis
      showed that both Alphaproteobacteria and Betaproteobacteria were abundant in the
      activated sludge, confirming that the two primer pairs target two different
      fractions of the bacterial community. Furthermore, terminal restriction fragment
      polymorphism analyses of a series of four activated sludge samples showed that
      the two primer pairs would have resulted in different conclusions about community
      stability and the factors contributing to changes in community composition. In
      conclusion, different PCR primer pairs, although considered universal, target
      different ranges of bacteria and will thus show the diversity and dynamics of
      different fractions of the bacterial community in the analyzed sample. We also
      show that while a database search can serve as an indicator of how universal a
      primer pair is, an experimental assessment is necessary to evaluate the
      suitability for a specific environmental sample. 

PMID- 24098499
TI  - Informing potential participants about research: observational study with an
      embedded randomized controlled trial.
AB  - OBJECTIVES: To assess: 1) the feasibility of electronic information provision; 2)
      gather evidence on the topics and level of detail of information potential
      research participant's accessed; 3) to assess satisfaction and understanding.
      DESIGN: Observational study with an embedded randomised controlled trial.
      SETTING: Low risk intervention study based in primary care. PARTICIPANTS: White
      British & Irish, South Asian and African-Caribbean subjects aged between 40-74
      years eligible for a blood pressure monitoring study. INTERVENTIONS: PDF copy of
      the standard paper participant information sheet (PDF-PIS) and an electronic
      Interactive Information Sheet (IIS) where participants could choose both the type
      and level of detail accessed. MAIN OUTCOME MEASURES: 1) Proportion of
      participants providing an email address and accessing electronic information 2)
      Willingness to participate in a recruitment clinic. 3) Type and depth of
      information accessed on the IIS. 4) Participant satisfaction and understanding.
      RESULTS: 1160 participants were eligible for the study. Of these, 276 (24%)
      provided an active email address, of whom 84 did not respond to the email. 106
      responded to the email but chose not to access any electronic information and
      were therefore ineligible for randomisation. 42 were randomised to receive the
      PDF-PIS and 44 to receive the IIS (with consent rates of 48% and 36%,
      respectively; odds ratio 0.6, 95% confidence interval 0.25 to 1.4). Electronic
      observation of information accessed by potential participants showed 41% chose to
      access no information and only 9% accessed the detail presented on the Research
      Ethics Committee approved participant information sheet before booking to attend
      a recruitment clinic for the intervention study. 63 of the 106 participants (59%)
      who chose not to access any electronic information also booked an appointment.
      CONCLUSIONS: Current written information about research may not be read,
      emphasising the importance of the consent interview and consideration of new ways
      of presenting complex information.

PMID- 24098500
TI  - Exploring leptin antagonism in ophthalmic cell models.
AB  - BACKGROUND: Emerging evidence suggests that angiogenic and pro-inflammatory
      cytokine leptin might be implicated in ocular neovascularization. However, the
      potential of inhibiting leptin function in ophthalmic cells has never been
      explored. Here we assessed mitogenic, angiogenic, and signaling leptin activities
      in retinal and corneal endothelial cells and examined the capability of a
      specific leptin receptor (ObR) antagonist, Allo-aca, to inhibit these functions.
      METHODS AND RESULTS: The experiments were carried out in monkey retinal (RF/6A)
      and bovine corneal (BCE) endothelial cells. Leptin at 50-250 ng/mL stimulated the
      growth of both cell lines in a dose-dependent manner. The maximal mitogenic
      response (35+/-7 and 27+/-3% in RF6A and BCE cells, respectively) was noted at 24
      h of 250 ng/mL leptin treatments. Leptin-dependent proliferation was reduced to
      base levels with 10 and 100 nM Allo-aca in BCE and RF6A cells, respectively. In
      both cell lines, leptin promoted angiogenic responses, with the maximal increase
      in tube formation (163+/-10 and 133+/-8% in RF6A and BCE cultures, respectively)
      observed under a 250 ng/mL leptin treatment for 3 h. Furthermore, in both cell
      lines 250 ng/mL leptin modulated the activity or expression of several signaling
      molecules involved in proliferation, inflammatory activity and angiogenesis, such
      as STAT3, Akt, and ERK1/2, COX2, and NFkappaB. In both cell lines, leptin-induced
      angiogenic and signaling responses were significantly inhibited with 100 nM Allo
      aca. We also found that leptin increased its own mRNA and protein expression in
      both cell lines, and this autocrine effect was abolished by 100-250 nM Allo-aca.
      CONCLUSIONS: Our data provide new insights into the role of leptin in ocular
      endothelial cells and represent the first original report on targeting ObR in
      ophthalmic cell models.

PMID- 24098501
TI  - Isolation and identification of algicidal compound from Streptomyces and
      algicidal mechanism to Microcystis aeruginosa.
AB  - The biological control of cyanobacterial harmful algal blooms (cyanoHABs) is
      important to promote human health, environmental protection, and economic growth.
      Active algicidal compounds and algicidal mechanisms should be identified and
      investigated to control cyanoHABs. In this study, the algicidal actinobacterium
      Streptomyces sp. L74 was isolated from the soil of a nearby pond which located in
      the center lake of Guanghzou Higher Education Mega Center. Results showed that
      the algicidal activities of cyanoHABs are mainly achieved via an indirect attack
      by producing algicidal compounds. All active algicidal compounds are hydrophilic
      substances that are heat and pH stable. In the present study, an active compound
      (B3) was isolated and purified by high-performance liquid chromatography and
      identified as a type of triterpenoid saponin (2-hydroxy-12-oleanene-3, 28-O-D
      glucopyranosyl) with a molecular formula of C42H70O13 as determined by infrared
      spectrometry, electrospray ionization mass spectrometry, and nuclear magnetic
      resonance. Active algicidal compounds from Streptomyces sp. L74 were shown to
      disrupt the antioxidant systems of Microcystis aeruginosa cells. 

PMID- 24098502
TI  - Spawning behaviour and post-spawning migration patterns of atlantic bluefin tuna
      (Thunnus thynnus) ascertained from satellite archival tags.
AB  - Spawning behaviour of Atlantic bluefin tuna (Thunnus thynnus) was investigated
      using electronic satellite tags deployed in the western Mediterranean spawning
      ground, around the Balearic Islands (years 2009-2011). All the fish were tagged
      underwater and released within schools. In general, the fish tagged in the same
      year/school displayed common migratory trends. Following extended residency
      around the Balearic Islands, most tagged tuna crossed the Strait of Gibraltar
      heading for the North Atlantic. Discrepancies between the migratory tracks
      reconstructed from this and previous electronic tagging studies suggest that the
      bluefin tuna Mediterranean population may comprise distinct units exhibiting
      differing migratory behaviours. The diving behaviour varied between oceanic
      regions throughout the migratory pathways, the shallowest distribution taking
      place in the spawning ground and the deepest at the Strait of Gibraltar. A unique
      diving pattern was found on the majority of nights while the fish stayed at the
      spawning ground; it consisted of frequent and brief oscillatory movements up and
      down through the mixed layer, resulting in thermal profiles characterized by
      oscillations about the thermocline. Such a pattern is believed to reflect recent
      courtship and spawning activity. Reproductive parameters inferred from the
      analysis of vertical profiles are consistent with those estimated in previous
      studies based on biological samples. 

PMID- 24098503
TI  - Beyond cell death - antiapoptotic Bcl-2 proteins regulate migration and invasion
      of colorectal cancer cells in vitro.
AB  - Migration and invasion of malignant cells are prerequisites for cancer
      progression and metastasis. The Bcl-2 family of proteins consists of about 25
      members and has been extensively studied in the context of apoptosis. Despite the
      fact that small molecules targeting Bcl-2 proteins have already entered clinical
      trials, very few studies investigated a role of antiapoptotic Bcl-2 proteins
      beside cell death in the context of metastasis. The aim of this study was to
      dissect a potential role of the antiapoptotic Bcl-2 proteins Mcl-1, Bcl-2 and Bcl
      xL on migration and invasion of colorectal cancer cells independent of their cell
      death control function. We used migration and invasion assays as well as three
      dimensional cell cultures to analyze colorectal cancer cell lines (HT29 and
      SW480) after siRNA mediated knockdown or overexpression of Mcl-1, Bcl-2 or Bcl
      xL. We observed neither spontaneous cell death induction nor impaired
      proliferation of cells lacking Mcl-1, Bcl-2 or Bcl-xL. In contrast, knockdown of
      Mcl-1 led to increased proliferation. Strikingly, we demonstrate a profound
      impairment of both, migration and invasion, of colorectal cancer cells after Mcl
      1, Bcl-2 or Bcl-xL knockdown. This phenotype was completely revised in cells
      overexpressing Mcl-1, Bcl-2 or Bcl-xL. The most pronounced effect among the
      investigated proteins was observed for Bcl-2. The data presented indicate a
      pivotal role of Mcl-1, Bcl-2 and Bcl-xL for migration and invasion of colorectal
      cancer cells independent of their known antiapoptotic effects. Thus, our study
      illustrates novel antitumoral mechanisms of Bcl-2 protein targeting. 

PMID- 24098504
TI  - Significantly increased risk of cardiovascular disease among patients with
      gallstone disease: a population-based cohort study.
AB  - OBJECTIVE: To investigate whether gallstone disease (GD) increases the risk of
      developing cardiovascular disease (CVD) in a large population-based cohort.
      METHODS: A study population including 6,981 patients with GD was identified from
      The Taiwan National Health Insurance Research Database between 2004 and 2005. GD
      patients were defined as patients with principal discharge diagnoses of
      cholelithiasis using the ICD-9-CM code 574. 27,924 patients without GD were
      randomly selected and matched for age and gender. All patients were followed for
      6 years or until diagnosis for CVD. Cox proportional hazards regression model was
      used to assess the risk of developing CVD with adjustment for age, gender and co
      morbid conditions. RESULTS: During the six years follow-up period, 935 patients
      with GD and 2,758 patients without GD developed CVD. Patients with GD had an
      elevated risk of CVD (HR, 1.32; 95% CI, 1.22-1.43) when compared with those
      without GD. Similar relationship was observed when CVD was categorized i.e.
      stroke (HR, 1.15; 95% CI, 1.01-1.32), coronary heart disease (HR, 1.42; 95% CI,
      1.28-1.58) and heart failure (HR, 1.31; 95% CI, 1.00-1.73). When GD was
      classified according to the level of severity, using patients without GD as
      reference, the risks of CVD were elevated in patients with non-severe GD (HR,
      1.34; 95% CI, 1.24-1.46) as well as those with severe GD (HR, 1.20, 95% CI, 1.02
      1.40), after adjusting for age, gender and comorbidities. In age-stratified
      analysis, patients aged 18-40 years with GD were at higher risk of developing CVD
      (HR, 1.42; 95% CI, 1.09-1.84) than older GD patients. CONCLUSION: This study
      found an increased risk of CVD in patients diagnosed with GD. The excess risk was
      particularly high in younger GD patients. Prevention of GD could help reduce the
      risk of developing CVD, and the better effect could be achieved for the younger
      age groups.

PMID- 24098505
TI  - Select dietary phytochemicals function as inhibitors of COX-1 but not COX-2.
AB  - Recent clinical trials raised concerns regarding the cardiovascular toxicity of
      selective cyclooxygenase-2 (COX-2) inhibitors. Many active dietary factors are
      reported to suppress carcinogenesis by targeting COX-2. A major question was
      accordingly raised: why has the lifelong use of phytochemicals that likely
      inhibit COX-2 presumably not been associated with adverse cardiovascular side
      effects. To answer this question, we selected a library of dietary-derived
      phytochemicals and evaluated their potential cardiovascular toxicity in human
      umbilical vein endothelial cells. Our data indicated that the possibility of
      cardiovascular toxicity of these dietary phytochemicals was low. Further
      mechanistic studies revealed that the actions of these phytochemicals were
      similar to aspirin in that they mainly inhibited COX-1 rather than COX-2,
      especially at low doses. 

PMID- 24098506
TI  - Downregulated expression of peroxiredoxin 4 in granulosa cells from polycystic
      ovary syndrome.
AB  - Peroxiredoxin 4 (PRDX4), a member of Peroxiredoxin (PRDX) family, is a typical 2
      Cys PRDX. PRDX4 monitors the oxidative burden within cellular compartment and
      reduces hydrogen peroxide and alkyl hydroperoxide related to oxidative stress and
      apoptosis. Antioxidant, like PRDX4, may promote follicle development and
      participate in the pathophysiology of PCOS. In our previous study, we found that
      PRDX4 was expressed in mice oocyte cumulus oophorus complex, and that PRDX4 could
      be associated with follicle development. In this study, we explored the
      expression of PRDX4 in human follicles and possible role of PRDX4 in PCOS
      pathophysiology. Our data showed that PRDX4 was mainly expressed in granulosa
      cells in human ovaries. When compared to control group, both PRDX4 mRNA level and
      protein level decreased in PCOS group. The lowered levels of PRDX4 may relate to
      oxidative stress in the pathophysiologic progress of PCOS. Furthermore,
      expression of PRDX4 in the granulosa cells of in vivo or in vitro matured
      follicles was higher than that in immatured follicles, which suggested that PRDX4
      may have a close relationship with follicular development. Altogether, our
      findings may provide new clues of the pathophysiologic mechanism of PCOS and
      potential therapeutic strategy using antioxidant, like PRDX4. 

PMID- 24098507
TI  - Netazepide, a gastrin receptor antagonist, normalises tumour biomarkers and
      causes regression of type 1 gastric neuroendocrine tumours in a nonrandomised
      trial of patients with chronic atrophic gastritis.
AB  - INTRODUCTION: Autoimmune chronic atrophic gastritis (CAG) causes hypochlorhydria
      and hypergastrinaemia, which can lead to enterochromaffin-like (ECL) cell
      hyperplasia and gastric neuroendocrine tumours (type 1 gastric NETs). Most behave
      indolently, but some larger tumours metastasise. Antrectomy, which removes the
      source of the hypergastrinaemia, usually causes tumour regression. Non-clinical
      and healthy-subject studies have shown that netazepide (YF476) is a potent,
      highly selective and orally-active gastrin/CCK-2 receptor antagonist. Also, it is
      effective in animal models of ECL-cell tumours induced by hypergastrinaemia. AIM:
      To assess the effect of netazepide on tumour biomarkers, number and size in
      patients with type I gastric NETs. METHODS: We studied 8 patients with multiple
      tumours and raised circulating gastrin and chromogranin A (CgA) concentrations in
      an open trial of oral netazepide for 12 weeks, with follow-up 12 weeks later. At
      0, 6, 12 and 24 weeks, we carried out gastroscopy, counted and measured tumours,
      and took biopsies to assess abundances of several ECL-cell constituents. At 0, 3,
      6, 9, 12 and 24 weeks, we measured circulating gastrin and CgA and assessed
      safety and tolerability. RESULTS: Netazepide was safe and well tolerated.
      Abundances of CgA (p<0.05), histidine decarboxylase (p<0.05) and matrix
      metalloproteinase-7(p<0.10) were reduced at 6 and 12 weeks, but were raised again
      at follow-up. Likewise, plasma CgA was reduced at 3 weeks (p<0.01), remained so
      until 12 weeks, but was raised again at follow-up. Tumours were fewer and the
      size of the largest one was smaller (p<0.05) at 12 weeks, and remained so at
      follow-up. Serum gastrin was unaffected. CONCLUSION: The reduction in abundances,
      plasma CgA, and tumour number and size by netazepide show that type 1 NETs are
      gastrin-dependent tumours. Failure of netazepide to increase serum gastrin
      further is consistent with achlorhydria. Netazepide is a potential new treatment
      for type 1 NETs. Longer, controlled trials are justified. TRIAL REGISTRATION:
      European Union EudraCT database 2007-002916-24
      https://www.clinicaltrialsregister.eu/ctr-search/search?query=2007-002916
      24ClinicalTrials.gov NCT01339169
      http://clinicaltrials.gov/ct2/show/NCT01339169?term=yf476&rank=5.

PMID- 24098508
TI  - Characteristic and functional analysis of toll-like receptors (TLRs) in the
      lophotrocozoan, Crassostrea gigas, reveals ancient origin of TLR-mediated innate
      immunity.
AB  - The evolution of TLR-mediated innate immunity is a fundamental question in
      immunology. Here, we report the characterization and functional analysis of four
      TLR members in the lophotrochozoans Crassostreagigas (CgTLRs). All CgTLRs bear a
      conserved domain organization and have a close relationship with TLRs in ancient
      non-vertebrate chordates. In HEK293 cells, every CgTLR could constitutively
      activate NF-kappaB responsive reporter, but none of the PAMPs tested could
      stimulate CgTLR-activated NF-kappaB induction. Subcellular localization showed
      that CgTLR members have similar and dual distribution on late endosomes and
      plasma membranes. Moreover, CgTLRs and CgMyD88 mRNA show a consistent response to
      multiple PAMP challenges in oyster hemocytes. As CgTLR-mediated NF-kappaB
      activation is dependent on CgMyD88, we designed a blocking peptide for CgTLR
      signaling that would inhibit CgTLR-CgMyD88 dependent NF-kappaB activation. This
      was used to demonstrate that a Vibrio parahaemolyticus infection-induced
      enhancement of degranulation and increase of cytokines TNF mRNA in hemocytes,
      could be inhibited by blocking CgTLR signaling. In summary, our study
      characterized the primitive TLRs in the lophotrocozoan C. gigas and demonstrated
      a fundamental role of TLR signaling in infection-induced hemocyte activation.
      This provides further evidence for an ancient origin of TLR-mediated innate
      immunity. 

PMID- 24098510
TI  - Mmp17b is essential for proper neural crest cell migration in vivo.
AB  - The extracellular matrix plays a critical role in neural crest (NC) cell
      migration. In this study, we characterize the contribution of the novel GPI
      linked matrix metalloproteinase (MMP) zebrafish mmp17b. Mmp17b is expressed post
      gastrulation in the developing NC. Morpholino inactivation of mmp17b function, or
      chemical inhibition of MMP activity results in aberrant NC cell migration with
      minimal change in NC proliferation or apoptosis. Intriguingly, a GPI anchored
      protein with metalloproteinase inhibitor properties, Reversion-inducing-Cysteine
      rich protein with Kazal motifs (RECK), which has previously been implicated in NC
      development, is expressed in close apposition to NC cells expressing mmp17b,
      raising the possibility that these two gene products interact. Consistent with
      this possibility, embryos silenced for mmp17b show defective development of the
      dorsal root ganglia (DRG), a crest-derived structure affected in RECK mutant fish
      sensory deprived (sdp). Taken together, this study has identified the first pair
      of MMP, and their putative MMP inhibitor RECK that functions together in NC cell
      migration. 

PMID- 24098509
TI  - Role of the spike glycoprotein of human Middle East respiratory syndrome
      coronavirus (MERS-CoV) in virus entry and syncytia formation.
AB  - Little is known about the biology of the emerging human group c betacoronavirus,
      Middle East Respiratory Syndrome coronavirus (MERS-CoV). Because coronavirus
      spike glycoproteins (S) mediate virus entry, affect viral host range, and elicit
      neutralizing antibodies, analyzing the functions of MERS-CoV S protein is a high
      research priority. MERS-CoV S on lentivirus pseudovirions mediated entry into a
      variety of cell types including embryo cells from New World Eptesicus fuscus
      bats. Surprisingly, a polyclonal antibody to the S protein of MHV, a group a
      murine betacoronavirus, cross-reacted in immunoblots with the S2 domain of group
      c MERS-CoV spike protein. MERS pseudovirions released from 293T cells contained
      only uncleaved S, and pseudovirus entry was blocked by lysosomotropic reagents
      NH4Cl and bafilomycin and inhibitors of cathepsin L. However, when MERS
      pseudovirions with uncleaved S protein were adsorbed at 4 degrees C to Vero E6
      cells, brief trypsin treatment at neutral pH triggered virus entry at the plasma
      membrane and syncytia formation. When 293T cells producing MERS pseudotypes co
      expressed serine proteases TMPRSS-2 or -4, large syncytia formed at neutral pH,
      and the pseudovirions produced were non-infectious and deficient in S protein.
      These experiments show that if S protein on MERS pseudovirions is uncleaved, then
      viruses enter by endocytosis in a cathepsin L-dependent manner, but if MERS-CoV S
      is cleaved, either during virus maturation by serine proteases or on
      pseudovirions by trypsin in extracellular fluids, then viruses enter at the
      plasma membrane at neutral pH and cause massive syncytia formation even in cells
      that express little or no MERS-CoV receptor. Thus, whether MERS-CoV enters cells
      within endosomes or at the plasma membrane depends upon the host cell type and
      tissue, and is determined by the location of host proteases that cleave the viral
      spike glycoprotein and activate membrane fusion. 

PMID- 24098511
TI  - Tetrandrine induces mitochondria-mediated apoptosis in human gastric cancer BGC
      823 cells.
AB  - Tetrandrine, a bis-benzylisoquinoline alkaloid isolated from the dried root of
      Hang-Fang-Chi (Stephaniatetrandra S. Moore), has been reported to possess anti
      cancer effects on many tumors. In this study, we investigated tetrandrine-induced
      apoptosis on human gastric cancer BGC-823 cells in vitro and in vivo. The results
      showed that tetrandrine significantly inhibited cell viability in a dose- and
      time-dependent manner and induced apoptosis. It increased the apoptosis;
      upregulation of Bax, Bak, and Bad; and downregulation of Bcl-2 and Bcl-xl in BGC
      823 cells. Moreover, tetrandrine increased the activation of caspase-3 and -9,
      release of cytochrome c, and upregulation of apaf-1, suggesting that tetrandrine
      induced apoptosis was related to the mitochondrial pathway. Meanwhile,
      pretreatment with the pan-caspase inhibitor z-VAD-fmk in BGC-823 cells reduced
      tetrandrine-induced apoptosis by blocking activation of caspases. Furthermore,
      tetrandrine effectively inhibited tumor growth via apoptosis induction, which was
      verified by immunohistochemical analysis in a nude mouse xenograft model. Taken
      together, we concluded that tetrandrine significantly inhibited the proliferation
      of gastric cancer BGC-823 cells through mitochondria-dependent apoptosis, which
      may play a promising role in gastric cancer therapy. 

PMID- 24098512
TI  - Transcriptomics of the rice blast fungus Magnaporthe oryzae in response to the
      bacterial antagonist Lysobacter enzymogenes reveals candidate fungal defense
      response genes.
AB  - Plants and animals have evolved a first line of defense response to pathogens
      called innate or basal immunity. While basal defenses in these organisms are well
      studied, there is almost a complete lack of understanding of such systems in
      fungal species, and more specifically, how they are able to detect and mount a
      defense response upon pathogen attack. Hence, the goal of the present study was
      to understand how fungi respond to biotic stress by assessing the transcriptional
      profile of the rice blast pathogen, Magnaporthe oryzae, when challenged with the
      bacterial antagonist Lysobacter enzymogenes. Based on microscopic observations of
      interactions between M. oryzae and wild-type L. enzymogenes strain C3, we
      selected early and intermediate stages represented by time-points of 3 and 9
      hours post-inoculation, respectively, to evaluate the fungal transcriptome using
      RNA-seq. For comparative purposes, we also challenged the fungus with L.
      enzymogenes mutant strain DCA, previously demonstrated to be devoid of antifungal
      activity. A comparison of transcriptional data from fungal interactions with the
      wild-type bacterial strain C3 and the mutant strain DCA revealed 463 fungal genes
      that were down-regulated during attack by C3; of these genes, 100 were also found
      to be up-regulated during the interaction with DCA. Functional categorization of
      genes in this suite included those with roles in carbohydrate metabolism,
      cellular transport and stress response. One gene in this suite belongs to the
      CFEM-domain class of fungal proteins. Another CFEM class protein called PTH11 has
      been previously characterized, and we found that a deletion in this gene caused
      advanced lesion development by C3 compared to its growth on the wild-type fungus.
      We discuss the characterization of this suite of 100 genes with respect to their
      role in the fungal defense response. 

PMID- 24098513
TI  - Default mode, dorsal attention and auditory resting state networks exhibit
      differential functional connectivity in tinnitus and hearing loss.
AB  - We investigated auditory, dorsal attention, and default mode networks in adults
      with tinnitus and hearing loss in a resting state functional connectivity study.
      Data were obtained using continuous functional magnetic resonance imaging (fMRI)
      while the participants were at "rest" and were not performing any task.
      Participants belonged to one of three groups: middle-aged adults with tinnitus
      and mild-to-moderate high frequency hearing loss (TIN), age-matched controls with
      normal hearing and no tinnitus (NH), and a second control group with mild-to
      moderate high frequency hearing loss without tinnitus (HL). After standard
      preprocessing, (a) a group independent component analysis (ICA) using 30
      components and (b) a seeding-based connectivity analysis were conducted. In the
      group ICA, the default mode network was the only network to display visual
      differences between subject groups. In the seeding analysis, we found increased
      connectivity between the left parahippocampus and the auditory resting state
      network in the TIN group when compared to NH controls. Similarly, there was also
      an increased correlation between the right parahippocampus and the dorsal
      attention network when compared to HL controls. Other group differences in this
      attention network included decreased correlations between the seed regions and
      the right supramarginal gyrus in TIN patients when compared to HL controls. In
      the default mode network, there was a strong decrease in correlation between the
      seed regions and the precuneus when compared to both control groups. The findings
      of this study identify specific alterations in the connectivity of the default
      mode, dorsal attention, and auditory resting state networks due to tinnitus. The
      results suggest that therapies for tinnitus that mitigate the increased
      connectivity of limbic regions with auditory and attention resting state networks
      and the decreased coherence of the default mode network could be effective at
      reducing tinnitus-related distress. 

PMID- 24098514
TI  - Enterovirus 74 infection in children.
AB  - Enterovirus 74 (EV74) is a rarely detected viral infection of children. In 2010,
      EV74 was identified in New Zealand in a 2 year old child with acute flaccid
      paralysis (AFP) through routine polio AFP surveillance. A further three cases of
      EV74 were identified in children within six months. These cases are the first
      report of EV74 in New Zealand. In this study we describe the near complete genome
      sequence of four EV74 isolates from New Zealand, which shows only limited
      sequence identity in the non-structural proteins when compared to the other two
      known EV74 sequences. As is typical of enteroviruses multiple recombination
      events were evident, particularly in the P2 region and P3 regions. This is the
      first complete EV74 genome sequenced from a patient with acute flaccid paralysis.

PMID- 24098515
TI  - Change in self-reported health status among immigrants in the United States:
      associations with measures of acculturation.
AB  - Although acculturation may have positive effects for immigrants, including better
      socioeconomic profiles and increased occupational opportunities, their health
      profiles deteriorate with longer duration in the U.S. Prior research indicates
      that increasing acculturation is associated with some poorer health outcomes
      among immigrants in the U.S. However, most of these studies have used length of
      stay or English language proficiency as proxies for acculturation, and have
      mainly examined self-reported "current" health outcomes. This study advances
      knowledge on associations between acculturation and health among immigrants by
      explicitly examining self-reported "change" in health since immigration, in
      relation to acculturation-related variables. We use data from the New Immigrant
      Survey (NIS; 2003-2004), a cross-sectional study of legal immigrants to the U.S.
      In addition to testing more conventionally examined proxies of acculturation
      (length of stay and English proficiency), we also examine English language use
      and self-reported change in diet. Multivariable logistic regression analyses on
      5,982 participants generally supported previous literature indicating a
      deleterious impact of acculturation, with increasing duration of stay and greater
      self-reported change in diet being associated with a poorer change in health
      since moving to the U.S. Although English language proficiency and use were
      associated with greater odds of reporting a worse change in health when examined
      individually, they were non-significant in multivariable models including all
      acculturation measures. Findings from this study suggest that when taking into
      account multiple measures of acculturation, language may not necessarily indicate
      unhealthy assimilation and dietary change may be a pathway leading to declines in
      immigrant health. Increasing duration in the U.S. may also reflect the adoption
      of unhealthy behaviors, as well as greater exposure to harmful sources of
      psychosocial stress including racial and anti-immigrant discrimination. Our study
      suggests that multiple indicators of acculturation may be useful in examining the
      effect of acculturation on changes in health among immigrants. 

PMID- 24098516
TI  - Misuse and dependence on non-prescription codeine analgesics or sedative H1
      antihistamines by adults: a cross-sectional investigation in France.
AB  - BACKGROUND: Given the growing worldwide market of non-prescription drugs,
      monitoring their misuse in the context of self-medication represents a particular
      challenge in Public Health. The aim of this study was to investigate the
      prevalence of misuse, abuse, and dependence on non-prescription psychoactive
      drugs. METHOD: During one month, in randomly solicited community pharmacies, an
      anonymous questionnaire was offered to adults requesting paracetamol (control
      group), codeine combined with paracetamol in analgesics, or sedative H1
      antihistamines. Responses about misuse (drug use not in agreement with the
      Patient Information Leaflet) abuse (excessive drug use having detrimental
      consequences), and dependence (established according to questions adapted from
      the Diagnostic and Statistical Manual of Mental Disorders, 4th Edition criteria)
      on psychoactive drugs were compared to those of the paracetamol control group.
      RESULTS: 295 patients (mean age 48.5 years, 68.5% of women) having used one of
      the studied drugs during the previous month were included. Misuse and dependence
      to codeine analgesics concerned 6.8% and 17.8% of the patients exposed to these
      drugs, respectively, (n = 118), which was significantly higher than for
      paracetamol. 19.5% had used codeine analgesics daily for more than six months.
      Headache was the most frequent reason for persistent daily use. A high prevalence
      of persistent daily users of sedative H1 antihistamines was also observed.
      Whereas these drugs are recommended only for short treatment courses of
      occasional insomnia, 72.2% of the participants having taken doxylamine (n = 36)
      were daily users, predominantly for more than six months. CONCLUSIONS: Results on
      misuse and dependence on non-prescription codeine analgesics suggest that chronic
      pain, in particular chronic cephalalgia, requires better medical care. In
      addition, as for hypnotics on prescription, persistent use of doxylamine for self
      medication is not justified until an acceptable benefit-risk ratio for chronic
      sleep disturbance is shown by clinical data.

PMID- 24098517
TI  - Improved detection of rare HIV-1 variants using 454 pyrosequencing.
AB  - 454 pyrosequencing, a massively parallel sequencing (MPS) technology, is often
      used to study HIV genetic variation. However, the substantial mismatch error rate
      of the PCR required to prepare HIV-containing samples for pyrosequencing has
      limited the detection of rare variants within viral populations to those present
      above ~1%. To improve detection of rare variants, we varied PCR enzymes and
      conditions to identify those that combined high sensitivity with a low error
      rate. Substitution errors were found to vary up to 3-fold between the different
      enzymes tested. The sensitivity of each enzyme, which impacts the number of
      templates amplified for pyrosequencing, was shown to vary, although not
      consistently across genes and different samples. We also describe an amplicon
      based method to improve the consistency of read coverage over stretches of the
      HIV-1 genome. Twenty-two primers were designed to amplify 11 overlapping
      amplicons in the HIV-1 clade B gag-pol and env gp120 coding regions to encompass
      4.7 kb of the viral genome per sample at sensitivities as low as 0.01-0.2%. 

PMID- 24098518
TI  - Influence of DNMT genotype on global and site specific DNA methylation patterns
      in neonates and pregnant women.
AB  - This study examines the relationship between common genetic variation within DNA
      methyltransferase genes and inter-individual variation in DNA methylation. Eleven
      polymorphisms spanning DNMT1 and DNMT3B were genotyped. Global and gene specific
      (IGF2, IGFBP3, ZNT5) DNA methylation was quantified by LUMA and bisulfite
      Pyrosequencing assays, respectively, in neonatal cord blood and in maternal
      peripheral blood. Associations between maternal genotype and maternal methylation
      (n (~) 333), neonatal genotype and neonatal methylation (n (~) 454), and maternal
      genotype and neonatal methylation (n (~) 137) were assessed. The findings of this
      study provide some support to the hypothesis that genetic variation in DNA
      methylating enzymes influence DNA methylation at global and gene-specific levels;
      however observations were not robust to correction for multiple testing. More
      comprehensive analysis of the influence of genetic variation on global and site
      specific DNA methylation is warranted. 

PMID- 24098519
TI  - Increased cytoplasmic localization of p27(kip1) and its modulation of RhoA
      activity during progression of chronic myeloid leukemia.
AB  - The role of p27(kip1) in Chronic Myeloid Leukemia (CML) has been well studied in
      relation to its function as a cell cycle inhibitor. However, its cytoplasmic
      function especially in CML remains to be seen. We studied the localization of
      p27(kip1) and its function during the progression of CML from chronic to blast
      phase. Our investigations revealed an increased localization of p27(kip1) in the
      cytoplasm of CD34(+) cells in the blast phase compared to chronic phase.
      Cytoplasmic p27(kip1) was found to modulate RhoA activity in CD34(+) stem and
      progenitor cells. Further, RhoA activity was shown to be dependent on cytoplasmic
      p27(kip1) which in turn was dependent on p210(Bcr-Abl) kinase activity.
      Interestingly, RhoA activity was observed to affect cell survival in the presence
      of imatinib through the SAPK/JNK pathway. Accordingly, inhibition of SAPK/JNK
      pathway using SP600125 increased apoptosis of K562 cells in presence of imatinib.
      Our results, for the first time, thus reveal a crucial link between cytoplasmic
      p27(kip1), RhoA activity and SAPK/JNK signalling. To this effect we observed a
      correlation between increased cytoplasmic p27(kip1), increased RhoA protein
      levels, decreased RhoA-GTP levels and increased SAPK/JNK phosphorylation in blast
      phase CD34(+) cells compared to chronic phase CD34(+) cells. 

PMID- 24098520
TI  - Identification and characterization of enhancer-blocking insulators to reduce
      retroviral vector genotoxicity.
AB  - The chromatin insulator cHS4 can reduce silencing chromosomal position effects
      and genotoxicity associated with integrating viral vectors. However, the fully
      active version of this element can also reduce vector titers and is only
      partially effective. In order to identify alternatives to cHS4, we developed a
      functional lentiviral vector-based reporter screen for enhancer-blocking
      insulators. Using this system, we screened candidate sequences that were
      initially identified by chromatin profiling for binding by CTCF and for DNase
      hypersensitivity. All 12 analyzed candidates blocked enhancer-promoter activity.
      The enhancer-blocking activity of the top two candidates was confirmed in two
      complementary plasmid-based assays. Studies in a gammaretroviral reporter vector
      indicated these two candidates have little to no effect on vector titers, and do
      not diminish vector expression in primary mouse bone marrow cultures. Subsequent
      assessment in a mouse in vivo tumor formation model demonstrated that both
      candidates reduced the rate of gammaretroviral vector-mediated genotoxicity as
      effectively as the cHS4 insulator. In summary, we have developed a novel
      lentiviral vector-based method of screening candidate elements for insulator
      activity, and have used this method to identify two new insulator elements
      capable of improving the safety of retroviral vectors without diminishing vector
      titers or expression. These findings expand the limited arsenal of insulators
      functionally validated to reduce the rate of retroviral vector-mediated
      genotoxicity. 

PMID- 24098521
TI  - Regulation of p53 by jagged1 contributes to angiotensin II-induced impairment of
      myocardial angiogenesis.
AB  - Angiotensin II (AngII) is a major contributor to the development of heart
      failure, however, the molecular and cellular mechanisms still remain elucidative.
      Inadequate angiogenesis in myocardium leads to transition from cardiac
      hypertrophy to dysfunction, this study was therefore conducted to examine the
      effects of AngII on myocardial angiogenesis and the underlying mechanisms. AngII
      treatment significantly impaired angiogenetic responses, which were determined by
      counting the capillaries either in matrigel formed by cultured cardiac
      microvascular endothelial cells (CMVECs) or in myocardium of mice and by
      measuring the in vitro and in vivo production of VEGF proteins, and stimulated
      accumulation and phosphorylation of cytosolic p53 which led to increases in
      phosphorylated p53 and decreases of hypoxia inducible factor (Hif-1) in nucleus.
      All of these cellular and molecular events induced by AngII in CEMCs and hearts
      of mice were largely reduced by a p53 inhibitor, pifithrin-alpha (PFT-alpha).
      Interestingly, AngII stimulated the upregulation of Jagged1, a ligand of Notch,
      but it didn't affect the expression of Delta-like 4 (Dll-4), another ligand of
      Notch. Inhibition of p53 by PFT-alpha partly abolished this effect of AngII.
      Further experiments showed that knockdown ofJagged1 by addition of siRNA to
      cultured CMVECs dramatically declined AngII-stimulated accumulation and
      phosphorylation of p53 in cytosol, upregulation of phosphorylated p53 and
      downregulation of Hif-1 expression in nucleus, decrease of VEGF production and
      impairment of capillary-like tube formation by the cells. Our data collectively
      suggest that AngII impairs myocardial angiogenetic responses through p53
      dependent downregulation of Hif-1 which is regulated by Jagged1/Notch1 signaling.

PMID- 24098522
TI  - Single incision versus conventional laparoscopic cholecystectomy outcomes: a meta
      analysis of randomized controlled trials.
AB  - BACKGROUND: Previous meta-analyses that compared the outcome of SILC and CLC have
      not presented consistent conclusions. This meta-analysis was performed after
      adding many recent RCTs, to clarify this issue. METHODS: Relevant articles
      published in English were identified by searching PubMed, Embase, Web of
      Knowledge, and the Cochrane Controlled Trial Register from January 1997 to
      February 2013. Reference lists of the retrieved articles were reviewed to
      identify additional articles. Primary outcomes (postoperative pain scores,
      cosmetic score, and length of incision) and secondary outcomes (operating time,
      blood loss, conversion rates, postoperative complications, postoperative hospital
      stay, time to initial oral intake, and time to resume work) were pooled.
      Quantitative variables were calculated using the weighted mean difference (WMD),
      and qualitative variables were pooled using odds ratios (OR). RESULTS: 25
      appropriate RCTs were identified from 2128 published articles. 1841 patients were
      treated, 944 with SILC and 897 with CLC. SILC was superior to CLC in cosmetic
      score (WMD = 1.155, P<0.001), shorter length of incision (WMD = -3.285, P =
      0.029), and postoperative pain within 12 h (VAS in 3-4 h, WMD = -0.704, P =
      0.026; VAS in 6-8 h, WMD = -0.613, P = 0.010). CLC was superior to SILC in
      operating time (OT) (WMD = 13.613, P<0.001) and need of additional instruments
      (OR = 7.448, P<0.001). Other secondary outcomes were similar. CONCLUSIONS: SILC
      offered a better cosmetic result and less postoperative pain for patients with
      uncomplicated cholelithiasis or polypoid lesions of the gallbladder. However,
      SILC was associated with a longer OT and required additional instruments.

PMID- 24098523
TI  - Systematic review of the performance of rapid rifampicin resistance testing for
      drug-resistant tuberculosis.
AB  - INTRODUCTION: Rapid tests for rifampicin resistance may be useful for identifying
      isolates at high risk of drug resistance, including multidrug-resistant TB (MDR
      TB). However, choice of diagnostic test and prevalence of rifampicin resistance
      may both impact a diagnostic strategy for identifying drug resistant-TB. We
      performed a systematic review to evaluate the performance of WHO-endorsed rapid
      tests for rifampicin resistance detection. METHODS: We searched MEDLINE, Embase
      and the Cochrane Library through January 1, 2012. For each rapid test, we
      determined pooled sensitivity and specificity estimates using a hierarchical
      random effects model. Predictive values of the tests were determined at different
      prevalence rates of rifampicin resistance and MDR-TB. RESULTS: We identified 60
      publications involving six different tests (INNO-LiPA Rif. TB assay, Genotype
      MTBDR assay, Genotype MTBDRplus assay, Colorimetric Redox Indicator (CRI) assay,
      Nitrate Reductase Assay (NRA) and MODS tests): for all tests, negative predictive
      values were high when rifampicin resistance prevalence was <= 30%. However,
      positive predictive values were considerably reduced for the INNO-LiPA Rif. TB
      assay, the MTBDRplus assay and MODS when rifampicin resistance prevalence was <
      5%. LIMITATIONS: In many studies, it was unclear whether patient selection or
      index test performance could have introduced bias. In addition, we were unable to
      evaluate critical concentration thresholds for the colorimetric tests.
      DISCUSSION: Rapid tests for rifampicin resistance alone cannot accurately predict
      rifampicin resistance or MDR-TB in areas with a low prevalence of rifampicin
      resistance. However, in areas with a high prevalence of rifampicin resistance and
      MDR-TB, these tests may be a valuable component of an MDR-TB management strategy.

PMID- 24098524
TI  - Perioperative challenges and surgical treatment of large simple, and infectious
      liver cyst - a 12-year experience.
AB  - BACKGROUND: Cystic lesions of the liver consist of a heterogeneous group of
      disorders that can present diagnostic and therapeutic challenges. METHODS: A
      retrospective review of all medical records of adult patients diagnosed with
      large (>7 cm) cystic lesions of the liver between January 2000 and December 2011,
      at Kurume University Hospital. Cases with polycystic disease were excluded.
      RESULTS: Twenty three patients were identified. The mean size was 13.9 cm (range,
      7-22cm). The majority of simple cysts were found in women (females: males, 2:
      21). In 19 patients, the cyst was removed surgically by wide deroofing
      (laparoscopically in 16 cases, combined with ethanol sclerotherapy in 13 cases).
      Infection of the liver cyst occurred in one patient, who later underwent central
      bi-segmentectomy. CONCLUSION: Simple large cysts of the liver can be successfully
      treated by laparoscopic deroofing and alcohol sclerotherapy. Large hepatic cyst
      considered to need drainage should be removed surgically to avoid possible
      infection.

PMID- 24098525
TI  - Simvastatin ameliorates liver fibrosis via mediating nitric oxide synthase in
      rats with non-alcoholic steatohepatitis-related liver fibrosis.
AB  - BACKGROUND: Simvastatin exerts pleiotropic effects on cardiovascular system.
      However, its effect on non-alcoholic fatty liver disease, especially the liver
      fibrosis, remains obscure. We aimed to clarify the relationship between
      simvastatin and liver fibrosis both in vivo and in vitro. METHODS: A High-fat
      diet was given to establish rat models with non-alcoholic steatohepatitis (NASH)
      related liver fibrosis and simvastatin (4mg.kg(-1).d(-1)) was administrated
      intragastrically until hepatic histological findings confirmed the appearance of
      fibrosis. Human hepatic stellate cell (HSC) line lx-2 cells were cultured in an
      adipogenic differentiating mixture (ADM) and then were treated with transforming
      growth factorbeta1 (TGF-beta1), served as a positive control, simvastatin, TGF
      beta1 plus simvastatin, Nomega-nitro-L-arginine methyl ester hydrochloride (L
      NAME, a inhibitor of nitric oxide synthase), and L-NAME plus simvastatin,
      respectively. The expressions of endothelial nitric oxide synthase (eNOS),
      inducible nitric oxide synthase (iNOS), and Collagen I as well as cellular alpha
      smooth muscle actin (alpha-SMA) were measured by real-time reverse transcriptase
      polymerase chain reaction (qRT-PCR) and Western blot in liver tissue and HSC.
      RESULTS: With the progress of NASH-related fibrosis, hepatic mRNA and protein
      expressions of iNOS, alpha-SMA, and Collagen I were increased while those of eNOS
      were decreased. Compared with model rats in 24(th) week group, rats in
      simvastatin group had less expressions of iNOS, alpha-SMA, and Collagen I and
      more expressions of eNOS. In vitro, LX-2 cells acquired quiescent phenotype when
      cultured in ADM, and TGF-beta1 could activate the quiescent HSC. Simvastatin
      inhibited LX-2 cells activation due to TGF-beta1 or L-NAME by increasing the
      expression of eNOS and decreasing the expression of iNOS. CONCLUSIONS:
      Simvastatin improves the prognosis of NASH-related fibrosis by increasing the
      expression of eNOS, decreasing the expression of iNOS, and inhibiting the
      activation of HSC.

PMID- 24098526
TI  - Amplified inhibition of stellate cell activation pathways by PPAR-gamma, RAR and
      RXR agonists.
AB  - Peroxisome proliferator activator receptors (PPAR) ligands such as 15-Delta12,13
      prostaglandin L(2) [PJ] and all trans retinoic acid (ATRA) have been shown to
      inhibit the development of liver fibrosis. The role of ligands of retinoic X
      receptor (RXR) and its ligand, 9-cis, is less clear. The purpose of this study
      was to investigate the effects of combined treatment of the three ligends, PJ,
      ATRA and 9-cis, on key events during liver fibrosis in rat primary hepatic
      stellate cells (HSCs). We found that the anti-proliferative effect of the
      combined treatment of PJ, ATRA and 9-cis on HSCs was additive. Further
      experiments revealed that this inhibition was due to cell cycle arrest at the
      G0/G1 phase as demonstrated by FACS analysis. In addition, the combined treatment
      reduced cyclin D1 expression and increased p21 and p27 protein levels.
      Furthermore, we found that the three ligands down regulated the phosphorylation
      of mTOR and p70(S6K). The activation of HSCs was also inhibited by the three
      ligands as shown by inhibition of vitamin A lipid droplets depletion from HSCs.
      Studies using real time PCR and western blot analysis showed marked inhibition of
      collagen Ialpha1 and alphaSMA by the combination of the three ligands. These
      findings suggest that the combined use of PJ, ATRA and 9-cis causes inhibition of
      cell proliferation by cell cycle arrest and down-regulation of fibrotic markers
      to a greater extent compared to each of the ligands alone. 

PMID- 24098528
TI  - Towards the burden of human leptospirosis: duration of acute illness and
      occurrence of post-leptospirosis symptoms of patients in the Netherlands.
AB  - BACKGROUND: Leptospirosis is a global zoonotic disease. Although important for
      the assessment of the burden of leptospirosis, data on the duration of the
      illness and the occurrence of post-leptospirosis complaints are not well
      documented. Hence the main objective of this study was to estimate the occurrence
      of persistent complaints and duration of hospital stay in laboratory confirmed
      leptospirosis patients in the Netherlands during 1985 to 2010. Additionally,
      several risk factors potentially impacting on the occurrence of post
      leptospirosis complaints were investigated. METHODS/PRINCIPAL FINDINGS: The
      duration of the acute phase of leptospirosis was 16 days (IQR 12-23); 10 days
      (IQR 7-16) were spent hospitalized. Eighteen fatal cases were excluded from this
      analysis. Complaints of leptospirosis patients by passive case investigations
      (CPC) derived from files on ambulant consultations occurring one month after
      hospital discharge, revealed persistent complaints in 108 of 236 (45.8%)
      laboratory confirmed cases. Data on persistent complaints after acute
      leptospirosis (PCAC), assessed in 225 laboratory confirmed leptospirosis cases
      collected through questionnaires during 1985-1993, indicated 68 (30.2%) PCAC
      cases. Frequently reported complaints included (extreme) fatigue, myalgia,
      malaise, headache, and a weak physical condition. These complaints prolonged in
      21.1% of the cases beyond 24 months after onset of disease. There was no
      association between post-leptospirosis complaints and hospitalization. However,
      individuals admitted at the intensive care unit (ICU) were twice as likely to
      have continuing complaints after discharge adjusting for age and dialysis (OR 2.0
      95% CI 0.8-4.8). No significant association could be found between prolongation
      of complaints and infecting serogroup, although subgroup analysis suggest that
      infection with serogroups Sejroe (OR 4.8, 95%CI 0.9-27.0) and icterohaemorrhagiae
      (OR 2.0, 95%CI 0.9-4.3 CI) are more likely to result in CPC than infections with
      serogroup Grippotyphosa. CONCLUSION/SIGNIFICANCE: In addition to the acute
      disease, persistent complaints have an impact on the burden of leptospirosis.

PMID- 24098527
TI  - Internalized gold nanoparticles do not affect the osteogenesis and apoptosis of
      MG63 osteoblast-like cells: a quantitative, in vitro study.
AB  - The long-term toxicity effects of gold nanoparticles (GNPs) on the proliferation
      and differentiation of a progenitor cell line, MG63 osteoblast-like cells, was
      investigated. These cells were treated for 20 hours with two media that contained
      10 nm GNPs at concentrations of 1 ppm and 10 ppm. The mitosis of the GNP-treated
      MG63 was observed after at least 21 hours using dark-field and fluorescence
      microscopy. The TEM, LSCM and dark-field hyperspectral images indicated that the
      late endosomes in cells that contained aggregated GNPs were caused by vesicle
      fusion. Subsequently, after 21 days of being cultured in fresh medium, the
      specific nodule-like phenotypes and bone-associated gene expression of the
      treated MG63 cells exhibited the same behaviors as those of the control group.
      Statistically, after 21 days, the viability of the treated cells was identical to
      that of the untreated ones. During the cell death program analysis, the apoptosis
      and necrosis percentages of cells treated for 8 or fewer days were also observed
      to exhibit no significant difference with those of the untreated cells. In
      summary, our experiments show that the long-term toxicity of GNPs on the
      osteogenetic differentiation of MG63 is low. In addition, because of their low
      toxicity and non-biodegradability, GNPs can potentially be used as biomarkers for
      the long-term optical observation of the differentiation of progenitor or stem
      cells based on their plasmonic light-scattering properties. 

PMID- 24098529
TI  - The human melanoma side population displays molecular and functional
      characteristics of enriched chemoresistance and tumorigenesis.
AB  - Melanoma remains the most lethal skin cancer, mainly because of high resistance
      to therapy. Side population (SP) cells are found in many types of cancer and are
      usually enriched in therapy-resistant as well as tumorigenic cells. Here, we
      identified a Hoechst dye-effluxing SP in a large series of human melanoma samples
      representing different progression phases. The SP size did not change with
      disease stage but was correlated with the prognostic "Breslow's depth" in the
      primary (cutaneous) tumors. When injected into immunodeficient mice, the SP
      generated larger tumors than the bulk "main population" (MP) melanoma cells in
      two consecutive generations, and showed tumorigenic capacity at lower cell
      numbers than the MP. In addition, the SP reconstituted the heterogeneous
      composition of the human A375 melanoma cell line, and its clonogenic activity was
      2.5-fold higher than that of the MP. Gene-expression analysis revealed
      upregulated expression in the melanoma SP (versus the MP) of genes associated
      with chemoresistance and anti-apoptosis. Consistent with these molecular
      characteristics, the SP increased in proportion when A375 cells were exposed to
      the melanoma standard chemotherapeutic agent dacarbazine, and to the aggravating
      condition of hypoxia. In addition, the SP showed enhanced expression of genes
      related to cell invasion and migration, as well as to putative (melanoma) cancer
      stem cells (CSC) including ABCB1 and JARID1B. ABCB1 immunoreactivity was detected
      in a number of tumor cells in human melanomas, and in particular in clusters at
      the invasive front of the primary tumors. Together, our findings support that the
      human melanoma SP is enriched in tumorigenic and chemoresistant capacity,
      considered key characteristics of CSC. The melanoma SP may therefore represent an
      interesting therapeutic target. 

PMID- 24098530
TI  - Adipocytokine profile, cytokine levels and foxp3 expression in multiple
      sclerosis: a possible link to susceptibility and clinical course of disease.
AB  - BACKGROUND: Adipocytokines may be involved in multiple sclerosis (MS) as well as
      other autoimmune and inflammatory-related diseases. This study aims to compare
      levels of resistin, visfatin and leptin in three subgroups of MS patients with
      healthy subjects and also to study their relationship with Foxp3 expression and
      levels of several pro-inflammatory mediators such as interleukine-1 beta(IL-1
      beta),tumor necrosis factor-alpha (TNF-alpha) and human sensitive C-reactive
      protein (hs-CRP). METHODS: A total of 391 subjects including 200 healthy controls
      and 191 MS patients were recruited for this case-control study. Circulating
      adipocytokines and inflammatory mediators were measured using immunoassay
      methods. Foxp3 gene expression in peripheral blood mononuclear cells (PBMC) was
      determined by quantitative real-time PCR. Fat tissue mass was evaluated by using
      dual energy X-ray absorptiometery (DEXA). RESULTS: A significant difference was
      observed in levels of inflammatory mediators, adipocytokines, Foxp3 gene
      expression and adipose tissue mass between MS patients and healthy controls. All
      adipocytokines were positively correlated with levels of inflammatory mediators
      and negatively correlated with Foxp3 expression in MS patients. In controls,
      there were positive correlations between circulating leptin and resistin with TNF
      alpha and IL-1beta in subgroup analysis, the highest levels of TNF-alpha, IL
      1beta, hs-CRP, resistin and leptin were observed in primary progressive-MS (PP
      MS) patients. Also, expression of Foxp3 and levels of visfatin in relapsing
      remitting-MS(RR-MS) patients were higher compared with the other subgroups.
      CONCLUSIONS: Our findings suggest the potential role of adipocytokines in
      pathogenesis and severity of MS. Notably, the relationship of adipocytokines
      levels with inflammatory cytokines as well as clinical features of MS could be
      considerable in translational medicine and biomarker studies.

PMID- 24098531
TI  - Physiological slowing and upregulation of inhibition in cortex are correlated
      with behavioral deficits in protein malnourished rats.
AB  - Protein malnutrition during early development has been correlated with cognitive
      and learning disabilities in children, but the neuronal deficits caused by long
      term protein deficiency are not well understood. We exposed rats from gestation
      up to adulthood to a protein-deficient (PD) diet, to emulate chronic protein
      malnutrition in humans. The offspring exhibited significantly impaired
      performance on the 'Gap-crossing' (GC) task after reaching maturity, a behavior
      that has been shown to depend on normal functioning of the somatosensory cortex.
      The physiological state of the somatosensory cortex was examined to determine
      neuronal correlates of the deficits in behavior. Extracellular multi-unit
      recording from layer 4 (L4) neurons that receive direct thalamocortical inputs
      and layers 2/3 (L2/3) neurons that are dominated by intracortical connections in
      the whisker-barrel cortex of PD rats exhibited significantly low spontaneous
      activity and depressed responses to whisker stimulation. L4 neurons were more
      severely affected than L2/3 neurons. The response onset was significantly delayed
      in L4 cells. The peak response latency of L4 and L2/3 neurons was delayed
      significantly. In L2/3 and L4 of the barrel cortex there was a substantial
      increase in GAD65 (112% over controls) and much smaller increase in NMDAR1 (12
      20%), suggesting enhanced inhibition in the PD cortex. These results show that
      chronic protein deficiency negatively affects both thalamo-cortical and cortico
      cortical transmission during somatosensory information processing. The findings
      support the interpretation that sustained protein deficiency interferes with
      features of cortical sensory processing that are likely to underlie the cognitive
      impairments reported in humans who have suffered from prolonged protein
      deficiency. 

PMID- 24098532
TI  - Selection of a novel anti-nicotine vaccine: influence of antigen design on
      antibody function in mice.
AB  - Anti-nicotine vaccines may aid smoking cessation via the induction of anti
      nicotine antibodies (Ab) which reduce nicotine entering the brain, and hence the
      associated reward. Ab function depends on both the quantity (titer) and the
      quality (affinity) of the Ab. Anti-nicotine vaccines tested previously in
      clinical studies had poor efficacy despite high Ab titer, and this may be due to
      inadequate function if Ab of low affinity were induced. In this study, we
      designed and synthesized a series of novel nicotine-like haptens which were all
      linked to diphtheria toxoid (DT) as carrier, but which differed in the site of
      attachment of linker to nicotine, the nature of linker used, and the handle used
      to attach the hapten to DT. The resulting hapten conjugates were evaluated in a
      mouse model, using CpG (a TLR9 agonist) and aluminum hydroxide (Al(OH)3) as
      adjuvants, whereby Ab titers, affinity and function were evaluated using a
      radiolabeled nicotine challenge model. A series of additional linkers varying in
      length, rigidity and polarity were used with a single hapten to generate
      additional DT-conjugates, which were also tested in mice. Conjugates made with
      different haptens resulted in various titers of anti-nicotine Ab. Several haptens
      gave similarly high Ab titers, but among these, Ab affinity and hence function
      varied considerably. Linker also influenced Ab titer, affinity and function.
      These results demonstrate that immune responses induced in mice by nicotine
      conjugate antigens are greatly influenced by hapten design including site of
      attachment of linker to nicotine, the nature of linker used, and the handle used
      to attach the hapten to DT. While both Ab titer and affinity contributed to
      function, affinity was more sensitive to antigen differences. 

PMID- 24098533
TI  - Effects of indole-3-acetic acid on the transcriptional activities and stress
      tolerance of Bradyrhizobium japonicum.
AB  - A genome-wide transcriptional profile of Bradyrhizobium japonicum, the nitrogen
      fixing endosymbiont of the soybean plant, revealed differential expression of
      approximately 15% of the genome after a 1 mM treatment with the phytohormone
      indole-3-acetic acid (IAA). A total of 1,323 genes were differentially expressed
      (619 up-regulated and 704 down-regulated) at a two-fold cut off with q value <=
      0.05. General stress response genes were induced, such as those involved in
      response to heat, cold, oxidative, osmotic, and desiccation stresses and in
      exopolysaccharide (EPS) biosynthesis. This suggests that IAA is effective in
      activating a generalized stress response in B. japonicum. The transcriptional
      data were corroborated by the finding that stress tolerance of B. japonicum in
      cell viability assays was enhanced when pre-treated with 1 mM IAA compared to
      controls. The IAA treatment also stimulated biofilm formation and EPS production
      by B. japonicum, especially acidic sugar components in the total EPS. The IAA pre
      treatment did not influence the nodulation ability of B. japonicum. The data
      provide a comprehensive overview of the potential transcriptional responses of
      the symbiotic bacterium when exposed to the ubiquitous hormone of its plant host.

PMID- 24098534
TI  - Neuroglobin over expressing mice: expression pattern and effect on brain ischemic
      infarct size.
AB  - BACKGROUND: Stroke is a major cause of death and severe disability, but effective
      treatments are limited. Neuroglobin, a neuronal heme-globin, has been advocated
      as a novel pharmacological target in combating stroke and neurodegenerative
      disorders based on cytoprotective properties. Using thoroughly validated
      antibodies and oligos, we give a detailed brain anatomical characterization of
      transgenic mice over expressing Neuroglobin. Moreover, using permanent middle
      artery occlusion the effect of elevated levels of Neuroglobin on ischemic damage
      was studied. Lastly, the impact of mouse strain genetic background on ischemic
      damage was investigated. PRINCIPAL FINDINGS: A four to five fold increase in
      Neuroglobin mRNA and protein expression was seen in the brain of transgenic mice.
      A beta-actin promoter was used to drive Neuroglobin over expression, but
      immunohistochemistry and in situ hybridization showed over expression to be
      confined to primarily the cortex, hippocampus, cerebellum, and only in neurons.
      The level and expression pattern of endogenous Neuroglobin was unaffected by
      insertion of the over expressing Ngb transgene. Neuroglobin over expression
      resulted in a significant reduction in infarct volume 24 hours after ischemia.
      Immunohistochemistry showed no selective sparing of Neuroglobin expressing cells
      in the ischemic core or penumbra. A significant difference in infarct volume was
      found between mice of the same strain, but from different colonies. SIGNIFICANCE:
      In contrast to some previous reports, Neuroglobin over expression is not global
      but confined to a few well-defined brain regions, and only in neurons. This study
      confirms previous reports showing a correlation between reduced infarct volume
      and elevated Neuroglobin levels, but underlines the need to study the likely
      contribution from compensatory mechanisms to the phenotype following a genetic
      perturbation. We also stress, that care should be taken when comparing results
      where different mouse strains and colonies have been used due to large genetic
      background contribution to the observed phenotype.

PMID- 24098535
TI  - Effects of rearing conditions on behaviour and endogenous opioids in rats with
      alcohol access during adolescence.
AB  - Causal links between early-life stress, genes and later psychiatric diagnoses are
      not possible to fully address in human studies. Animal models therefore provide
      an important complement in which conditions can be well controlled and are here
      used to study and distinguish effects of early-life stress and alcohol exposure.
      The objective of this study was to investigate the impact of rearing conditions
      on behaviour in young rats and if these changes could be followed over time and
      to examine interaction effects between early-life environment and adolescent
      alcohol drinking on behaviour and immunoreactive levels of the opioid peptides
      dynorphin B, met-enkephalin-Arg(6)Phe(7) and beta-endorphin. We employed a rodent
      model, maternal separation, to study the impact of rearing conditions on
      behaviour, voluntary alcohol consumption and alcohol-induced effects. The
      consequences of short, 15 min (MS 15), and long, 360 min (MS 360), maternal
      separation in combination with adolescent voluntary alcohol consumption on
      behaviour and peptides were examined. A difference in the development of risk
      taking behaviour was found between the MS15 and MS360 while the development of
      general activity was found to differ between intake groups. Beta-endorphin levels
      in the pituitary and the periaqueductal gray area was found to be higher in the
      MS15 than the MS360. Adolescent drinking resulted in higher dynorphin B levels in
      the hippocampus and higher met-enkephalin-Arg(6)Phe(7) levels in the amygdala.
      Amygdala and hippocampus are involved in addiction processes and changes in these
      brain areas after adolescent alcohol drinking may have consequences for cognitive
      function and drug consumption behaviour in adulthood. The study shows that
      individual behavioural profiling over time in combination with neurobiological
      investigations provides means for studies of causality between early-life stress,
      behaviour and vulnerability to psychiatric disorders. 

PMID- 24098536
TI  - Acid ceramidase promotes nuclear export of PTEN through sphingosine 1-phosphate
      mediated Akt signaling.
AB  - The tumor suppressor PTEN is now understood to regulate cellular processes at the
      cytoplasmic membrane, where it classically regulates PI3K signaling, as well as
      in the nucleus where multiple roles in controlling cell cycle and genome
      stability have been elucidated. Mechanisms that dictate nuclear import and, less
      extensively, nuclear export of PTEN have been described, however the relevance of
      these processes in disease states, particularly cancer, remain largely unknown.
      We investigated the impact of acid ceramidase on the nuclear-cytoplasmic
      trafficking of PTEN. Immunohistochemical analysis of a human prostate tissue
      microarray revealed that nuclear PTEN was lost in patients whose tumors had
      elevated acid ceramidase. We found that acid ceramidase promotes a reduction in
      nuclear PTEN that is dependent upon sphingosine 1-phosphate-mediated activation
      of Akt. We were further able to show that sphingosine 1-phosphate promotes
      formation of a complex between Crm1 and PTEN, and that leptomycin B prevents acid
      ceramidase and sphingosine 1-phosphate mediated loss of nuclear PTEN, suggesting
      an active exportin-mediated event. To investigate whether the tumor promoting
      aspects of acid ceramidase in prostate cancer depend upon its ability to export
      PTEN from the nucleus, we used enforced nuclear expression of PTEN to study
      docetaxel-induced apoptosis and cell killing, proliferation, and xenoengraftment.
      Interestingly, while acid ceramidase was able to protect cells expressing wild
      type PTEN from docetaxel, promote proliferation and xenoengraftment, acid
      ceramidase had no impact in cells expressing PTEN-NLS. These findings suggest
      that acid ceramidase, through sphingosine 1-phosphate, promotes nuclear export of
      PTEN as a means of promoting tumor formation, cell proliferation, and resistance
      to therapy. 

PMID- 24098537
TI  - An organic acid based counter selection system for cyanobacteria.
AB  - Cyanobacteria are valuable organisms for studying the physiology of
      photosynthesis and carbon fixation, as well as metabolic engineering for the
      production of fuels and chemicals. This work describes a novel counter selection
      method for the cyanobacterium Synechococcus sp. PCC 7002 based on organic acid
      toxicity. The organic acids acrylate, 3-hydroxypropionate, and propionate were
      shown to be inhibitory towards Synechococcus sp. PCC 7002 and other cyanobacteria
      at low concentrations. Inhibition was overcome by a loss of function mutation in
      the gene acsA, which is annotated as an acetyl-CoA ligase. Loss of AcsA function
      was used as a basis for an acrylate counter selection method. DNA fragments of
      interest were inserted into the acsA locus and strains harboring the insertion
      were isolated on selective medium containing acrylate. This methodology was also
      used to introduce DNA fragments into a pseudogene, glpK. Application of this
      method will allow for more advanced genetics and engineering studies in
      Synechococcus sp. PCC 7002 including the construction of markerless gene
      deletions and insertions. The acrylate counter-selection could be applied to
      other cyanobacterial species where AcsA activity confers acrylate sensitivity
      (e.g. Synechocystis sp. PCC 6803). 

PMID- 24098538
TI  - Knockdown of lymphoid enhancer factor 1 inhibits colon cancer progression in
      vitro and in vivo.
AB  - Expression of lymphoid enhancer factor 1 (LEF1) is frequently altered in
      different human cancers. This study aimed to assess LEF1 expression in colon
      cancer tissues and to explore changed phenotypes, gene expressions, and the
      possible mechanism after knocked down LEF1 expression in colon cancer cell lines.
      A total of 106 colon cancer and matched paratumorous normal tissues were used to
      assess LEF1 expression using immunohistochemistry and qRT-PCR. LEF1 lentivirus
      was used to knockdown LEF1 expression for the assessment of cell viability, cell
      cycle distribution, apoptosis, and gene expressions. The nude mouse xenograft
      assay was performed to detect the effects of LEF1 knockdown in vivo. The data
      showed that the levels of LEF1 mRNA and protein were significantly increased in
      human colon cancer tissues compared to the matched paratumorous normal tissues
      and were associated with infiltration depth, lymph node and distant metastases,
      advanced TNM (tumor-node-metastasis) stages, and shorter overall survival.
      Furthermore, LEF1 knockdown reduced tumor cell viability, invasion capacity, MMP2
      and MMP-9 expression, but induced apoptosis. Nude mouse xenograft assay showed
      that LEF1 knockdown suppressed tumor formation and growth in vivo. In addition,
      the expression of Notch pathway-related proteins RBP-jkappa and Hes1 was reduced
      in LEF1 knockdown cells. Taken together, LEF1 protein was overexpressed in colon
      cancer tissues and knockdown of LEF1 expression inhibited colon cancer growth in
      vitro and in vivo. These data suggest that targeting of LEF1 expression should be
      further evaluated for colon cancer prevention and therapy. 

PMID- 24098539
TI  - Autophagy induced by HIF1alpha overexpression supports trophoblast invasion by
      supplying cellular energy.
AB  - Extravillous trophoblasts (EVTs) characterize the invasion of the maternal
      decidua under low oxygen and poor nutrition at the early feto-maternal interface
      to establish a successful pregnancy. We previously reported that autophagy in
      EVTs was activated under 2% O2 in vitro, and autophagy activation was also
      observed in EVTs at the early feto-maternal interface in vivo. Here, we show that
      autophagy is an energy source for the invasion of EVTs. Cobalt chloride (CoCl2),
      which induces hypoxia inducible factor 1alpha (HIF1alpha) overexpression,
      activated autophagy in HTR8/SVneo cells, an EVT cell line. The number of invading
      HTR8-ATG4B(C74A) cells, an autophagy-deficient EVT cell line, was markedly
      reduced by 81 percent with the CoCl2 treatment through the suppression of MMP9
      level, although CoCl2 did not affect the cellular invasion of HTR8-mStrawberry
      cells, a control cell line. HTR8-ATG4B(C74A) cells treated with CoCl2 showed a
      decrease in cellular adenosine triphosphate (ATP) levels and a compensatory
      increase in the expression of purinergic receptor P2X ligand-gated ion channel 7
      (P2RX7), which is stimulated with ATP, whereas HTR8-mStrawberry cells maintained
      cellular ATP levels and did not affect P2RX7 expression. Furthermore, the
      decreased invasiveness of HTR8-ATG4B(C74A) cells treated with CoCl2 was
      neutralized by ATP supplementation to the level of HTR8-ATG4B(C74A) cells treated
      without CoCl2. These results suggest that autophagy plays a role in maintaining
      homeostasis by countervailing HIF1alpha-mediated cellular energy consumption in
      EVTs. 

PMID- 24098540
TI  - Fodrin in centrosomes: implication of a role of fodrin in the transport of gamma
      tubulin complex in brain.
AB  - Gamma-tubulin is the major protein involved in the nucleation of microtubules
      from centrosomes in eukaryotic cells. It is present in both cytoplasm and
      centrosome. However, before centrosome maturation prior to mitosis, gamma-tubulin
      concentration increases dramatically in the centrosome, the mechanism of which is
      not known. Earlier it was reported that cytoplasmic gamma-tubulin complex
      isolated from goat brain contains non-erythroid spectrin/fodrin. The major role
      of erythroid spectrin is to help in the membrane organisation and integrity.
      However, fodrin or non-erythroid spectrin has a distinct pattern of localisation
      in brain cells and evidently some special functions over its erythroid
      counterpart. In this study, we show that fodrin and gamma-tubulin are present
      together in both the cytoplasm and centrosomes in all brain cells except
      differentiated neurons and astrocytes. Immunoprecipitation studies in purified
      centrosomes from brain tissue and brain cell lines confirm that fodrin and gamma
      tubulin interact with each other in centrosomes. Fodrin dissociates from
      centrosome just after the onset of mitosis, when the concentration of gamma
      tubulin attains a maximum at centrosomes. Further it is observed that the
      interaction between fodrin and gamma-tubulin in the centrosome is dependent on
      actin as depolymerisation of microfilaments stops fodrin localization. Image
      analysis revealed that gamma-tubulin concentration also decreased drastically in
      the centrosome under this condition. This indicates towards a role of fodrin as a
      regulatory transporter of gamma-tubulin to the centrosomes for normal progression
      of mitosis. 

PMID- 24098541
TI  - Identifying three ecological chemotypes of Xanthium strumarium glandular
      trichomes using a combined NMR and LC-MS method.
AB  - Xanthanolides, as the sesquiterpene lactones, are reportedly the major components
      for the pharmacological properties of X. strumarium L. species. Phytochemical
      studies indicated that the glandular structures on the surface of plant tissues
      would form the primary sites for the accumulation of this class of the compounds.
      As the interface between plants and their natural enemies, glandular trichomes
      may vary with respect to which of their chemicals are sequestered against
      different herbivores in different ecologies. However, to date, no data are
      available on the chemical characterisation of X. strumarium glandular cells. In
      this study, the trichome secretions of the X. strumarium species originating from
      nineteen unique areas across eleven provinces in China, were analysed by HPLC, LC
      ESI-MS and NMR. For the first time three distinct chemotypes of X. strumarium
      glandular trichomes were discovered along with the qualitative and quantitative
      evaluations of their presence of xanthanolides; these were designated glandular
      cell Types I, II, and III, respectively. The main xanthanolides in Type I cells
      were 8-epi-xanthatin and xanthumin while no xanthatin was detected. Xanthatin, 8
      epi-xanthatin, and xanthumin dominated in Type II cells with comparable levels of
      each being present. For Type III cells, significantly higher concentrations of 8
      epi-xanthatin or xanthinosin (relative to xanthatin) were detected with
      xanthinosin only being observed in this type. Further research will focus on
      understanding the ecological and molecular mechanism causing these chemotype
      differences in X. strumarium glandular structures. 

PMID- 24098542
TI  - Intrinsically disordered and aggregation prone regions underlie beta-aggregation
      in S100 proteins.
AB  - S100 proteins are small dimeric calcium-binding proteins which control cell
      cycle, growth and differentiation via interactions with different target
      proteins. Intrinsic disorder is a hallmark among many signaling proteins and S100
      proteins have been proposed to contain disorder-prone regions. Interestingly,
      some S100 proteins also form amyloids: S100A8/A9 forms fibrils in prostatic
      inclusions and S100A6 fibrillates in vitro and seeds SOD1 aggregation. Here we
      report a study designed to investigate whether beta-aggregation is a feature
      extensive to more members of S100 family. In silico analysis of seven human S100
      proteins revealed a direct correlation between aggregation and intrinsic disorder
      propensity scores, suggesting a relationship between these two independent
      properties. Averaged position-specific analysis and structural mapping showed
      that disorder-prone segments are contiguous to aggregation-prone regions and that
      whereas disorder is prominent on the hinge and target protein-interaction
      regions, segments with high aggregation propensity are found in ordered regions
      within the dimer interface. Acidic conditions likely destabilize the seven S100
      studied by decreasing the shielding of aggregation-prone regions afforded by the
      quaternary structure. In agreement with the in silico analysis, hydrophobic
      moieties become accessible as indicated by strong ANS fluorescence. ATR-FTIR
      spectra support a structural inter-conversion from alpha-helices to
      intermolecular beta-sheets, and prompt ThT-binding takes place with no noticeable
      lag phase. Dot blot analysis using amyloid conformational antibodies denotes a
      high diversity of conformers; subsequent analysis by TEM shows fibrils as
      dominant species. Altogether, our data suggests that beta-aggregation and
      disorder-propensity are related properties in S100 proteins, and that the onset
      of aggregation is likely triggered by loss of protective tertiary and quaternary
      interactions. 

PMID- 24098543
TI  - Isolation and characterization of microsatellite loci for the isopod crustacean
      Armadillidium vulgare and transferability in terrestrial isopods.
AB  - Armadillidium vulgare is a terrestrial isopod (Crustacea, Oniscidea) which
      harbors Wolbachia bacterial endosymbionts. A. vulgare is the major model for the
      study of Wolbachia-mediated feminization of genetic males in crustaceans. As a
      consequence of their impact on host sex determination mechanisms, Wolbachia
      endosymbionts are thought to significantly influence A. vulgare evolution on
      various grounds, including population genetic structure, diversity and
      reproduction strategies. To provide molecular tools for examining these
      questions, we isolated microsatellite loci through 454 pyrosequencing of a repeat
      enriched A. vulgare genomic library. We selected 14 markers and developed three
      polymorphic microsatellite multiplex kits. We tested the kits on two A. vulgare
      natural populations and found high genetic variation, thereby making it possible
      to investigate the impact of Wolbachia endosymbionts on A. vulgare nuclear
      variation at unprecedented resolution. In addition, we tested the transferability
      of these kits by cross-species amplification in five other terrestrial isopod
      species harboring Wolbachia endosymbionts. The microsatellite loci showed good
      transferability in particular in Armadillidium nasatum and Chaetophiloscia
      elongata, for which these markers represent promising tools for future genetic
      studies. 

PMID- 24098544
TI  - The CpG island in the murine foxl2 proximal promoter is differentially methylated
      in primary and immortalized cells.
AB  - Forkhead box L2 (Foxl2), a member of the forkhead transcription factor family,
      plays important roles in pituitary follicle-stimulating hormone synthesis and in
      ovarian maintenance and function. Mutations in the human FOXL2 gene cause eyelid
      malformations and premature ovarian failure. FOXL2/Foxl2 is expressed in
      pituitary gonadotrope and thyrotrope cells, the perioptic mesenchyme of the
      developing eyelid, and ovarian granulosa cells. The mechanisms governing this
      cell-restricted expression have not been described. We mapped the Foxl2
      transcriptional start site in immortalized murine gonadotrope-like cells,
      LbetaT2, by 5' rapid amplification of cDNA ends and then PCR amplified
      approximately 1 kb of 5' flanking sequence from murine genomic DNA. When ligated
      into a reporter plasmid, the proximal promoter conferred luciferase activity in
      both homologous (LbetaT2) and, unexpectedly, heterologous (NIH3T3) cells. In
      silico analyses identified a CpG island in the proximal promoter and 5'
      untranslated region, suggesting that Foxl2 transcription might be regulated
      epigenetically. Indeed, pyrosequencing and quantitative analysis of DNA
      methylation using real-time PCR revealed Foxl2 proximal promoter hypomethylation
      in homologous compared to some, though not all, heterologous cell lines. The
      promoter was also hypomethylated in purified murine gonadotropes. In vitro
      promoter methylation completely silenced reporter activity in heterologous and
      homologous cells. Collectively, the data suggest that differential proximal
      promoter DNA methylation may contribute to cell-specific Foxl2 expression in some
      cellular contexts. However, gonadotrope-specific expression of the gene cannot be
      explained by promoter hypomethylation alone. 

PMID- 24098545
TI  - CYP2D6 genotype and tamoxifen response for breast cancer: a systematic review and
      meta-analysis.
AB  - OBJECTIVE: To evaluate evidence on the association between CYP2D6 genotype and
      tamoxifen response through. DESIGN: Systematic review and meta-analysis of
      prospective, cross-sectional and case-control studies published to 2012. For each
      study, relative risks and 95% confidence intervals were extracted and pooled with
      a fixed and random effects model. Heterogeneity, publication bias, subgroup, and
      meta-regression analyses were performed. DATA SOURCES: PubMed (inception-2012)
      and EMBASE (inception-2012). ELIGIBILITY CRITERIA FOR SELECTING STUDIES: Criteria
      for inclusion were studies reporting breast cancer outcomes in patients treated
      with tamoxifen and genotyped for polymorphisms in the CYP2D6 gene. RESULTS:
      Twenty-five studies of 13,629 individuals were identified, of which 22
      investigated the association of CYP2D6 genotype with outcomes in breast cancer
      women all receiving tamoxifen treatment ("treatment-only" design). Three
      randomized trials evaluated the effect of CYP2D6 genotype on tamoxifen response
      ("effect modification" design). In analysis of treatment-only studies, the
      relative risk (RR) of all-cause mortality (>307 events in 4,936 patients) for
      carriers of a CYP2D6 reduced function allele was 1.11 (95% confidence interval
      (CI): 0.94 to 1.31) compared to individuals with normal/increased function CYP2D6
      alleles. When we investigated a composite outcome including all-cause mortality
      and surrogate endpoints for overall survival (>307 events in 6,721 patients),
      carriers of a CYP2D6 reduced function allele had a RR of 1.27 (95% CI: 1.11 to
      1.45). From two randomized trials that permitted effect-modification analysis,
      one had only 154 patients and showed evidence of effect modification of tamoxifen
      by CYP2D6 genotype for distant recurrence but was directionally opposite to that
      predicted, whereas a larger trial of 2,537 patients failed to show evidence of
      effect modification for breast cancer-free interval (P values for interaction
      0.02 and 0.44, respectively). CONCLUSIONS: Based on these findings, there is
      insufficient evidence to recommend CYP2D6 genotyping to guide tamoxifen
      treatment.

PMID- 24098546
TI  - Comparative efficacy and acceptability of antidepressants in Parkinson's disease:
      a network meta-analysis.
AB  - BACKGROUND: Depression is a common non-motor symptom in patients with Parkinson's
      disease (PD). There are many kinds of antidepressants being used, such as
      tricyclic antidepressants (TCAs), selective serotonin reuptake inhibitors
      (SSRIs), serotonin and norepinephrine reuptake inhibitors (SNRIs), and Dopamine
      agonists which are suggested as alternative antidepressants for the treatment of
      depression in PD. Which one should we choose first? Literatures have shown
      inconsistent results. METHODS: We conducted a network meta-analysis of randomized
      controlled trials to compare the efficacy and acceptability of therapeutic
      methods for the treatment of depression in Parkinson's disease. RESULTS: We used
      the odds ratios (OR) as effect size firstly and the results indicated no
      statistical significance between each compared intervention. Then we used the
      logarithm of the individual odds ratios as effect size. With efficacy of TCAs as
      the standard of comparison, the degree of incoherence (a measure of how closely
      the entire network fits together) was small (omega =  4.824827e-05). The logor
      were: SSRIs -0.69 (95% CI -1.28- -0.10); Pramipexole -0.73 (-1.71- -0.26);
      Pergolide -1.97 (-3.67- 0.27); SNRIs -0.86 (-1.86- 0.15); Placebo -1.24 (-1.99- 
      0.50). With Placebo as the standard of comparison, the logor were: TCAs 1.24
      (0.50- 1.99); SSRIs 0.55 (-0.03- 1.13); Pramipexole 0.51 (-0.12- 1.15); Pergolide
      -0.73 (-2.25- 0.80); SNRIs 0.38 (-0.42- 1.19); TCAs, pramipexole, pergolide and
      SNRIs showed better profile of acceptability, leading to significant fewer
      discontinuations than that of SSRIs. CONCLUSIONS: There is insufficient evidence
      to support antidepressant efficacy for SSRIs, pramipexole, pergolide and SNRIs.
      TCAs might be the best choice when starting antidepressant treatment in patients
      of Parkinson's disease because it has the most favorable balance between benefits
      and acceptability, followed by pramipexole and SNRIs, SSRIs might be the last
      choice.

PMID- 24098547
TI  - Graphical tools for network meta-analysis in STATA.
AB  - Network meta-analysis synthesizes direct and indirect evidence in a network of
      trials that compare multiple interventions and has the potential to rank the
      competing treatments according to the studied outcome. Despite its usefulness
      network meta-analysis is often criticized for its complexity and for being
      accessible only to researchers with strong statistical and computational skills.
      The evaluation of the underlying model assumptions, the statistical
      technicalities and presentation of the results in a concise and understandable
      way are all challenging aspects in the network meta-analysis methodology. In this
      paper we aim to make the methodology accessible to non-statisticians by
      presenting and explaining a series of graphical tools via worked examples. To
      this end, we provide a set of STATA routines that can be easily employed to
      present the evidence base, evaluate the assumptions, fit the network meta
      analysis model and interpret its results. 

PMID- 24098548
TI  - Protein disulfide isomerase interacts with tau protein and inhibits its
      fibrillization.
AB  - BACKGROUND: Tau protein is implicated in the pathogenesis of neurodegenerative
      disorders such as tauopathies including Alzheimer disease, and Tau fibrillization
      is thought to be related to neuronal toxicity. Physiological inhibitors of Tau
      fibrillization hold promise for developing new strategies for treatment of
      Alzheimer disease. Because protein disulfide isomerase (PDI) is both an enzyme
      and a chaperone, and implicated in neuroprotection against Alzheimer disease, we
      want to know whether PDI can prevent Tau fibrillization. In this study, we have
      investigated the interaction between PDI and Tau protein and the effect of PDI on
      Tau fibrillization. METHODOLOGY/PRINCIPAL FINDINGS: As evidenced by co
      immunoprecipitation and confocal laser scanning microscopy, human PDI interacts
      and co-locates with some endogenous human Tau on the endoplasmic reticulum of
      undifferentiated SH-SY5Y neuroblastoma cells. The results from isothermal
      titration calorimetry show that one full-length human PDI binds to one full
      length human Tau (or human Tau fragment Tau244-372) monomer with moderate,
      micromolar affinity at physiological pH and near physiological ionic strength. As
      revealed by thioflavin T binding assays, Sarkosyl-insoluble SDS-PAGE, and
      transmission electron microscopy, full-length human PDI remarkably inhibits both
      steps of nucleation and elongation of Tau244-372 fibrillization in a
      concentration-dependent manner. Furthermore, we find that two molecules of the a
      domain of human PDI interact with one Tau244-372 molecule with sub-micromolar
      affinity, and inhibit both steps of nucleation and elongation of Tau244-372
      fibrillization more strongly than full-length human PDI.
      CONCLUSIONS/SIGNIFICANCE: We demonstrate for the first time that human PDI binds
      to Tau protein mainly through its thioredoxin-like catalytic domain a, forming a
      1?1 complex and preventing Tau misfolding. Our findings suggest that PDI could
      act as a physiological inhibitor of Tau fibrillization, and have applications for
      developing novel strategies for treatment and early diagnosis of Alzheimer
      disease.

PMID- 24098549
TI  - Fumaric acid esters stimulate astrocytic VEGF expression through HIF-1alpha and
      Nrf2.
AB  - Fumaric acid esters (FAE) are oral analogs of fumarate that have recently been
      shown to decrease relapse rate and disease progression in multiple sclerosis
      (MS), prompting to investigate their protective potential in other neurological
      diseases such as amyotrophic lateral sclerosis (ALS). Despite efficacy in MS,
      mechanisms of action of FAEs are still largely unknown. FAEs are known to
      activate the transcription factor Nrf2 and downstream anti-oxidant responses
      through the succination of Nrf2 inhibitor KEAP1. However, fumarate is also a
      known inhibitor of prolyl-hydroxylases domain enzymes (PhD), and PhD inhibition
      might lead to stabilization of the HIF-1alpha transcription factor under normoxic
      conditions and subsequent activation of a pseudo hypoxic response. Whether Nrf2
      activation is associated with HIF-1alpha stabilization in response to FAEs in
      cell types relevant to MS or ALS remains unknown. Here, we show that FAEs elicit
      HIF-1alpha accumulation, and VEGF release as its expected consequence, in
      astrocytes but not in other cell types of the central nervous system. Reporter
      assays demonstrated that increased astrocytic VEGF release in response to FAEs
      was dependent upon both HIF-1alpha and Nrf2 activation. Last, astrocytes of
      transgenic mice expressing SOD1(G93A), an animal model of ALS, displayed reduced
      VEGF release in response to FAEs. These studies show that FAEs elicit different
      signaling pathways in cell types from the central nervous system, in particular a
      pseudo-hypoxic response in astrocytes. Disease relevant mutations might affect
      this response. 

PMID- 24098550
TI  - Are organic falls bridging reduced environments in the deep sea? - results from
      colonization experiments in the Gulf of Cadiz.
AB  - Organic falls create localised patches of organic enrichment and disturbance
      where enhanced degradation is mediated by diversified microbial assemblages and
      specialized fauna. The view of organic falls as "stepping stones" for the
      colonization of deep-sea reducing environments has been often loosely used, but
      much remains to be proven concerning their capability to bridge dispersal among
      such environments. Aiming the clarification of this issue, we used an
      experimental approach to answer the following questions: Are relatively small
      organic falls in the deep sea capable of sustaining taxonomically and trophically
      diverse assemblages over demographically relevant temporal scales? Are there
      important depth- or site-related sources of variability for the composition and
      structure of these assemblages? Is the proximity of other reducing environments
      influential for their colonization? We analysed the taxonomical and trophic
      diversity patterns and partitioning (alpha- and beta-diversity) of the
      macrofaunal assemblages recruited in small colonization devices with organic and
      inorganic substrata after 1-2 years of deployment on mud volcanoes of the Gulf of
      Cadiz. Our results show that small organic falls can sustain highly diverse and
      trophically coherent assemblages for time periods allowing growth to reproductive
      maturity, and successive generations of dominant species. The composition and
      structure of the assemblages showed variability consistent with their
      biogeographic and bathymetric contexts. However, the proximity of cold seeps had
      limited influence on the similarity between the assemblages of these two habitats
      and organic falls sustained a distinctive fauna with dominant substrate-specific
      taxa. We conclude that it is unlikely that small organic falls may regularly
      ensure population connectivity among cold seeps and vents. They may be a
      recurrent source of evolutionary candidates for the colonization of such
      ecosystems. However, there may be a critical size of organic fall to create the
      necessary intense and persistent reducing conditions for sustaining typical
      chemosymbiotic vent and seep organisms. 

PMID- 24098552
TI  - Increased serum adipokines implicate chronic inflammation in the pathogenesis of
      overactive bladder syndrome refractory to antimuscarinic therapy.
AB  - OBJECTIVES: Recent studies have shown that chronic inflammation is involved in
      overactive bladder (OAB) syndrome. OAB could be a subtype of neurogenic
      inflammation. This pilot study investigated serum adipokine levels in patients
      with OAB refractory to antimuscarinic therapy. METHODS: Thirty consecutive
      patients with OAB-dry (n = 16) or OAB-wet (n = 14) refractory to previous
      antimuscarinic treatment were prospectively enrolled in this study, a group of 26
      normal subjects without lower urinary tract symptoms served as controls.
      Concentrations of serum C-reactive protein (CRP), nerve growth factor (NGF), and
      adipokines including interleukins ([IL], IL-1beta, IL-6, IL-8), tumor necrosis
      factor (TNF)-alpha, monocyte chemotactic protein (MCP)-1, insulin, and leptin
      were quantified using a bead-based human serum adipokine panel B kit. Data were
      analyzed using the LX 200 platform. Patients were further classified as having
      dry or wet OAB and having medical diseases or not. The serum CRP, NGF, and
      adipokine levels were compared between OAB patients and the controls, and between
      OAB subgroups. RESULTS: The serum concentrations of CRP, NGF, IL-1beta, IL-6, IL
      8, and TNF-alpha in OAB-dry and OAB-wet patients were significantly higher than
      among the controls. There was no significant difference in adipokine levels
      between OAB-dry and OAB-wet, or between OAB patients with and without medical
      diseases. Serum CRP and NGF levels were significantly higher only in OAB-wet or
      OAB patients with medical diseases than among controls. The MCP-1 levels, on the
      other hand, were significantly higher in OAB-dry or OAB patients with disease,
      than the controls. CONCLUSIONS: Both OAB-dry and OAB-wet patients showed
      increased serum CRP, NGF, and adipokine levels compared with the controls,
      suggesting chronic inflammation of the bladder involving both peripheral and
      central mechanisms in all OAB patients refractory to antimuscarinic therapy. The
      increased serum adipokine levels were not relevant to medical diseases.

PMID- 24098551
TI  - Long term metabolic syndrome induced by a high fat high fructose diet leads to
      minimal renal injury in C57BL/6 mice.
AB  - Metabolic syndrome can induce chronic kidney disease in humans. Genetically
      engineered mice on a C57BL/6 background are highly used for mechanistic studies.
      Although it has been shown that metabolic syndrome induces cardiovascular lesions
      in C57BL/6 mice, in depth renal phenotyping has never been performed. Therefore
      in this study we characterized renal function and injury in C57BL/6 mice with
      long-term metabolic syndrome induced by a high fat and fructose diet (HFFD).
      C57BL/6 mice received an 8 months HFFD diet enriched with fat (45% energy from
      fat) and drinking water enriched with fructose (30%). Body weight, food/water
      consumption, energy intake, fat/lean mass ratio, plasma glucose, HDL, LDL,
      triglycerides and cholesterol levels were monitored. At 3, 6 and 8 months, renal
      function was determined by inulin clearance and measure of albuminuria. At
      sacrifice, kidneys and liver were collected. Metabolic syndrome in C57BL/6 mice
      fed a HFFD was observed as early 4 weeks with development of type 2 diabetes at 8
      weeks after initiation of diet. However, detailed analysis of kidney structure
      and function showed only minimal renal injury after 8 months of HFFD. HFFD
      induced moderate glomerular hyperfiltration (436,4 uL/min vs 289,8 uL/min; p
      value=0.0418) together with a 2-fold increase in albuminuria only after 8 months
      of HFFD. This was accompanied by a 2-fold increase in renal inflammation (p
      value=0.0217) but without renal fibrosis or mesangial matrix expansion. In
      addition, electron microscopy did not show alterations in glomeruli such as basal
      membrane thickening and foot process effacement. Finally, comparison of the
      urinary peptidome of these mice with the urinary peptidome from humans with
      diabetic nephropathy also suggested absence of diabetic nephropathy in this
      model. This study provides evidence that the HFFD C57BL/6 model is not the
      optimal model to study the effects of metabolic syndrome on the development of
      diabetic kidney disease. 

PMID- 24098553
TI  - Circulating levels of human salusin-beta, a potent hemodynamic and atherogenesis
      regulator.
AB  - Using bioinformatics analysis, we previously identified salusin-beta, an
      endogenous bioactive peptide with diverse physiological activities. Salusin-beta
      is abundantly expressed in the neuroendocrine system and in systemic endocrine
      cells/macrophages. Salusin-beta acutely regulates hemodynamics and chronically
      induces atherosclerosis, but its unique physicochemical characteristics to
      tightly adhere to all types of plastic and glassware have prevented elucidation
      of its precise pathophysiological role. To quantitate plasma total salusin-beta
      concentrations, we produced rabbit and chicken polyclonal antibodies against the
      C- and N-terminal end sequences, circumvented its sticky nature, and successfully
      established a sandwich enzyme-linked immunosorbent assay (ELISA). Salusin-beta
      was abundantly present in the plasma of healthy volunteers, ranging from 1.9 to
      6.6 nmol/L. Reverse phase-high performance liquid chromatography analysis showed
      that a single immunoreactive salusin-beta peak coincided with synthetic authentic
      salusin-beta. Plasma salusin-beta concentrations were unaffected by postural
      changes and by potent vasopressin release stimuli, such as hypertonic saline
      infusion or smoking. However, salusin-beta concentrations showed significant
      circadian variation; concentrations were high during the daytime and reached the
      lowest concentrations in the early morning. Plasma salusin-beta levels in
      subjects with diabetes mellitus, coronary artery disease, and cerebrovascular
      disease showed distinctly higher levels than healthy controls. Patients with
      panhypopituitarism combined with complete central diabetes insipidus also showed
      significantly higher plasma salusin-beta levels. Therefore, the ELISA system
      developed in this study will be useful for evaluating circulating total salusin
      beta levels and for confirming the presence of authentic salusin-beta in human
      plasma. The obtained results suggest a limited contribution of the neuroendocrine
      system to peripheral total salusin-beta concentrations and a role for plasma
      total salusin-beta concentrations as an indicator of systemic vascular diseases. 

PMID- 24098554
TI  - Alterations of red cell membrane properties in neuroacanthocytosis.
AB  - Neuroacanthocytosis (NA) refers to a group of heterogenous, rare genetic
      disorders, namely chorea acanthocytosis (ChAc), McLeod syndrome (MLS),
      Huntington's disease-like 2 (HDL2) and pantothenate kinase associated
      neurodegeneration (PKAN), that mainly affect the basal ganglia and are associated
      with similar neurological symptoms. PKAN is also assigned to a group of rare
      neurodegenerative diseases, known as NBIA (neurodegeneration with brain iron
      accumulation), associated with iron accumulation in the basal ganglia and
      progressive movement disorder. Acanthocytosis, the occurrence of misshaped
      erythrocytes with thorny protrusions, is frequently observed in ChAc and MLS
      patients but less prevalent in PKAN (about 10%) and HDL2 patients. The
      pathological factors that lead to the formation of the acanthocytic red blood
      cell shape are currently unknown. The aim of this study was to determine whether
      NA/NBIA acanthocytes differ in their functionality from normal erythrocytes.
      Several flow-cytometry-based assays were applied to test the physiological
      responses of the plasma membrane, namely drug-induced endocytosis,
      phosphatidylserine exposure and calcium uptake upon treatment with
      lysophosphatidic acid. ChAc red cell samples clearly showed a reduced response in
      drug-induced endovesiculation, lysophosphatidic acid-induced phosphatidylserine
      exposure, and calcium uptake. Impaired responses were also observed in
      acanthocyte-positive NBIA (PKAN) red cells but not in patient cells without shape
      abnormalities. These data suggest an "acanthocytic state" of the red cell where
      alterations in functional and interdependent membrane properties arise together
      with an acanthocytic cell shape. Further elucidation of the aberrant molecular
      mechanisms that cause this acanthocytic state may possibly help to evaluate the
      pathological pathways leading to neurodegeneration. 

PMID- 24098555
TI  - Does an 'activity-permissive' workplace change office workers' sitting and
      activity time?
AB  - INTRODUCTION: To describe changes in workplace physical activity, and health-,
      and work-related outcomes, in workers who transitioned from a conventional to an
      'activity-permissive' workplace. METHODS: A natural pre-post experiment conducted
      in Vancouver, Canada in 2011. A convenience sample of office-based workers (n=24,
      75% women, mean [SD] age = 34.5 [8.1] years) were examined four months following
      relocation from a conventional workplace (pre) to a newly-constructed, purpose
      built, movement-oriented physical environment (post). Workplace activity-
      (activPAL3-derived stepping, standing, and sitting time), health- (body
      composition and fasting cardio-metabolic blood profile), and work- (performance;
      job satisfaction) related outcomes were measured pre- and post-move and compared
      using paired t-tests. RESULTS: Pre-move, on average (mean [SD]) the majority of
      the day was spent sitting (364 [43.0] mins/8-hr workday), followed by standing
      (78.2 [32.1] mins/8-hr workday) and stepping (37.7 [15.6] mins/8-hr workday). The
      transition to the 'activity-permissive' workplace resulted in a significant
      increase in standing time (+18.5, 95% CI: 1.8, 35.2 mins/8-hr workday), likely
      driven by reduced sitting time (-19.7, 95% CI: -42.1, 2.8 mins/8-hr workday)
      rather than increased stepping time (+1.2, 95% CI: -6.2, 8.5 mins/8-hr workday).
      There were no statistically significant differences observed in health- or work
      related outcomes. DISCUSSION: This novel, opportunistic study demonstrated that
      the broader workplace physical environment can beneficially impact on standing
      time in office workers. The long-term health and work-related benefits, and the
      influence of individual, organizational, and social factors on this change,
      requires further evaluation.

PMID- 24098556
TI  - Antimicrobial constituents of the leaves of Mikania micrantha H. B. K.
AB  - BACKGROUND: To isolate plant-derived compounds with antimicrobial activity from
      the leaves of Mikania micrantha, to determine the compounds configuration, and to
      evaluate their antimicrobial activity against eight plant pathogenic fungi
      (Exserohilum turcicum, Colletotrichum lagenarium, Pseudoperonispora cubensis,
      Botrytis cirerea, Rhizoctonia solani, Phytophthora parasitica, Fusarium solani,
      and Pythium aphanidermatum,) and four plant pathogenic bacteria (gram negative
      bacteria: Ralstonia dolaanacearum, Xanthomonas oryzae pv. Oryzae, Xanthomonas
      Campestris pv. Vesicatoria, and Xanthomonas campestris pv. Citri), and four
      bacteria (gram positive bacteria: Staphyloccocus aureus, Bacillus subtilis,
      Micrococcus luteus, and Bacillus cereus). METHODS AND RESULTS: Antimicrobial
      constituents of the leaves of M. micrantha were isolated using bioactivity-
      guided fractionation. The antifungal activity of the isolated compounds was
      evaluated by the inhibit hypha growth method and inhibit spore germination
      method. Characterization of antibacterial activity was carried out using the
      minimum inhibitory concentrations (MICs) and the minimum bactericidal
      concentrations (MBCs). MIC and MBC were determined by the broth microdilution
      method. Six compounds - deoxymikanolide, scandenolide, dihydroscandenolide,
      mikanolide, dihydromikanolide, and m - methoxy benzoic acid - have been isolated
      from leaves of Mikania micrantha H. B. K. Deoxymikanolide, scandenolide, and
      dihydroscandenolide were new compounds. The result of bioassay showed that all of
      isolated compounds were effective against tested strains and deoxymikanolide
      showed the strongest activity. CONCLUSIONS AND SIGNIFICANCE: The leaves of M.
      micrantha may be a promising source in the search for new antimicrobial drugs due
      to its efficacy and the broadest range. Meanwhile, adverse impact of M. micrantha
      will be eliminated.

PMID- 24098557
TI  - Comparative molecular docking analysis of cytoplasmic dynein light chain DYNLL1
      with pilin to explore the molecular mechanism of pathogenesis caused by
      Pseudomonas aeruginosa PAO.
AB  - Cytoplasmic dynein light chain 1 (DYNLL1) is a component of large protein
      complex, which is implicated in cargo transport processes, and is known to
      interact with many cellular and viral proteins through its short consensus motif
      (K/R)XTQT. Still, it remains to be explored that bacterial proteins also exhibit
      similar recognition sequences to make them vulnerable to host defense mechanism.
      We employed multiple docking protocols including AUTODOCK, PatchDock, ZDOCK,
      DOCK/PIERR and CLUSPRO to explore the DYNLL1 and Pilin interaction followed by
      molecular dynamics simulation assays. Subsequent structural comparison of the
      predicted binding site for DYNLL1-Pilin complex against the experimentally
      verified DYNLL1 binding partners was performed to cross check the residual
      contributions and to determine the binding mode. On the basis of in silico
      analysis, here we describe a novel interaction of DYNLL1 and receptor binding
      domain of Pilin (the main protein constituent of bacterial type IV Pili) of gram
      negative bacteria Pseudomonas aeruginosa (PAO), which is the third most common
      nosocomial pathogen associated with the life-threatening infections. Evidently,
      our results underscore that Pilin specific motif (KSTQD) exhibits a close
      structural similarity to that of Vaccinia virus polymerase, P protein Rabies and
      P protein Mokola viruses. We speculate that binding of DYNLL1 to Pilin may
      trigger an uncontrolled inflammatory response of the host immune system during P.
      aeruginosa chronic infections thereby opening a new pioneering area to
      investigate the role of DYNLL1 in gram negative bacterial infections other than
      viral infections. Moreover, by manifesting a strict correspondence between
      sequence and function, our study anticipates a novel drug target site to control
      the complications caused by P. aeruginosa infections. 

PMID- 24098558
TI  - Intracellular ATP concentration contributes to the cytotoxic and cytoprotective
      effects of adenosine.
AB  - Extracellular adenosine (ADE) interacts with cells by two pathways: by activating
      cell surface receptors at nanomolar/micromolar concentrations; and by interfering
      with the homeostasis of the intracellular nucleotide pool at millimolar
      concentrations. Ade shows both cytotoxic and cytoprotective effects; however, the
      underlying mechanisms remain unclear. In the present study, the effects of
      adenosine-mediated ATP on cell viability were investigated. Adenosine treatment
      was found to be cytoprotective in the low intracellular ATP state, but cytotoxic
      under the normal ATP state. Adenosine-mediated cytotoxicity and cytoprotection
      rely on adenosine-derived ATP formation, but not via the adenosine receptor
      pathway. Ade enhanced proteasome inhibition-induced cell death mediated by ATP
      generation. These data provide a new pathway by which adenosine exerts dual
      biological effects on cell viability, suggesting an important role for adenosine
      as an ATP precursor besides the adenosine receptor pathway.

PMID- 24098560
TI  - Aortic stiffness in lone atrial fibrillation: a novel risk factor for arrhythmia
      recurrence.
AB  - BACKGROUND: Recent community-based research has linked aortic stiffness to the
      development of atrial fibrillation. We posit that aortic stiffness contributes to
      adverse atrial remodeling leading to the persistence of atrial fibrillation
      following catheter ablation in lone atrial fibrillation patients, despite the
      absence of apparent structural heart disease. Here, we aim to evaluate aortic
      stiffness in lone atrial fibrillation patients and determine its association with
      arrhythmia recurrence following radio-frequency catheter ablation. METHODS: We
      studied 68 consecutive lone atrial fibrillation patients who underwent catheter
      ablation procedure for atrial fibrillation and 50 healthy age- and sex-matched
      community controls. We performed radial artery applanation tonometry to obtain
      central measures of aortic stiffness: pulse pressure, augmentation pressure and
      augmentation index. Following ablation, arrhythmia recurrence was monitored at
      months 3, 6, 9, 12 and 6 monthly thereafter. RESULTS: Compared to healthy
      controls, lone atrial fibrillation patients had significantly elevated peripheral
      pulse pressure, central pulse pressure, augmentation pressure and larger left
      atrial dimensions (all P<0.05). During a mean follow-up of 2.9+/-1.4 years, 38 of
      the 68 lone atrial fibrillation patients had atrial fibrillation recurrence after
      initial catheter ablation procedure. Neither blood pressure nor aortic stiffness
      indices differed between patients with and without atrial fibrillation
      recurrence. However, patients with highest levels (>=75(th) percentile) of
      peripheral pulse pressure, central pulse pressure and augmentation pressure had
      higher atrial fibrillation recurrence rates (all P<0.05). Only central aortic
      stiffness indices were associated with lower survival free from atrial
      fibrillation using Kaplan-Meier analysis. CONCLUSION: Aortic stiffness is an
      important risk factor in patients with lone atrial fibrillation and contributes
      to higher atrial fibrillation recurrence following catheter ablation procedure.

PMID- 24098559
TI  - Additional antiepileptic mechanisms of levetiracetam in lithium-pilocarpine
      treated rats.
AB  - Several studies have addressed the antiepileptic mechanisms of levetiracetam
      (LEV); however, its effect on catecholamines and the inflammatory mediators that
      play a role in epilepsy remain elusive. In the current work, lithium (Li)
      pretreated animals were administered LEV (500 mg/kg i.p) 30 min before the
      induction of convulsions by pilocarpine (PIL). Li-PIL-induced seizures were
      accompanied by increased levels of hippocampal prostaglandin (PG) E2,
      myeloperoxidase (MPO), tumor necrosis factor-alpha, and interleukin-10. Moreover,
      it markedly elevated hippocampal lipid peroxides and nitric oxide levels, while
      it inhibited the glutathione content. Li-PIL also reduced hippocampal
      noradrenaline, as well as dopamine contents. Pretreatment with LEV protected
      against Li-PIL-induced seizures, where it suppressed the severity and delayed the
      onset of seizures in Li-PIL treated rats. Moreover, LEV reduced PGE2 and MPO, yet
      it did not affect the level of both cytokines in the hippocampus. LEV also
      normalized hippocampal noradrenaline, dopamine, glutathione, lipid peroxides, and
      nitric oxide contents. In conclusion, alongside its antioxidant property, LEV
      anticonvulsive effect involves catecholamines restoration, as well as inhibition
      of PGE2, MPO, and nitric oxide. 

PMID- 24098561
TI  - Recrudescence mechanisms and gene expression profile of the reproductive tracts
      from chickens during the molting period.
AB  - The reproductive system of chickens undergoes dynamic morphological and
      functional tissue remodeling during the molting period. The present study
      identified global gene expression profiles following oviductal tissue regression
      and regeneration in laying hens in which molting was induced by feeding high
      levels of zinc in the diet. During the molting and recrudescence processes,
      progressive morphological and physiological changes included regression and re
      growth of reproductive organs and fluctuations in concentrations of testosterone,
      progesterone, estradiol and corticosterone in blood. The cDNA microarray analysis
      of oviductal tissues revealed the biological significance of gene expression
      based modulation in oviductal tissue during its remodeling. Based on the gene
      expression profiles, expression patterns of selected genes such as, TF, ANGPTL3,
      p20K, PTN, AvBD11 and SERPINB3 exhibited similar patterns in expression with
      gradual decreases during regression of the oviduct and sequential increases
      during resurrection of the functional oviduct. Also, miR-1689* inhibited
      expression of Sp1, while miR-17-3p, miR-22* and miR-1764 inhibited expression of
      STAT1. Similarly, chicken miR-1562 and miR-138 reduced the expression of ANGPTL3
      and p20K, respectively. These results suggest that these differentially regulated
      genes are closely correlated with the molecular mechanism(s) for development and
      tissue remodeling of the avian female reproductive tract, and that miRNA-mediated
      regulation of key genes likely contributes to remodeling of the avian
      reproductive tract by controlling expression of those genes post
      transcriptionally. The discovered global gene profiles provide new molecular
      candidates responsible for regulating morphological and functional recrudescence
      of the avian reproductive tract, and provide novel insights into understanding
      the remodeling process at the genomic and epigenomic levels. 

PMID- 24098562
TI  - Intracellular regulation of cross-presentation during dendritic cell maturation.
AB  - We have investigated the effect of different maturation stimuli on the ability of
      mature dendritic cells (DCs) to cross-present newly acquired particulate
      antigens. Cross-presentation was impaired in DCs matured by treatment with TNF
      alpha, CpG and LPS, but was less affected upon CD40L-induced maturation. The
      difference could not be explained by decreased antigen uptake or translocation
      into the cytosol, but decreased cross-presentation ability did correlate with
      increased phagosomal/lysosomal acidification. Nevertheless, intra-phagosomal
      degradation of OVA was not increased in matured samples, suggesting that
      decreasing phagosomal pH may also regulate cross-presentation by a mechanism
      other than enhancing degradation. 

PMID- 24098563
TI  - Use of a safe, reproducible, and rapid aerosol delivery method to study infection
      by Burkholderia pseudomallei and Burkholderia mallei in mice.
AB  - Burkholderia pseudomallei, the etiologic agent of melioidosis, is a saprophytic
      bacterium readily isolated from wet soils of countries bordering the equator.
      Burkholderia mallei is a host-adapted clone of B. pseudomallei that does not
      persist outside of its equine reservoir and causes the zoonosis glanders, which
      is endemic in Asia, Africa, the Middle East and South America. Infection by these
      organisms typically occurs via percutaneous inoculation or inhalation of
      aerosols, and the most common manifestation is severe pneumonia leading to fatal
      bacteremia. Glanders and melioidosis are difficult to diagnose and require
      prolonged antibiotic therapy with low success rates. There are no vaccines
      available to protect against either Burkholderia species, and there is concern
      regarding their use as biological warfare agents given that B. mallei has
      previously been utilized in this manner. Hence, experiments were performed to
      establish a mouse model of aerosol infection to study the organisms and develop
      countermeasures. Using a hand-held aerosolizer, BALB/c mice were inoculated
      intratracheally with strains B. pseudomallei 1026b and B. mallei ATCC23344 and
      growth of the agents in the lungs, as well as dissemination to the spleen, were
      examined. Mice infected with 10(2), 10(3) and 10(4) organisms were unable to
      control growth of B. mallei in the lungs and bacteria rapidly disseminated to the
      spleen. Though similar results were observed in mice inoculated with 10(3) and
      10(4) B. pseudomallei cells, animals infected with 10(2) organisms controlled
      bacterial replication in the lungs, dissemination to the spleen, and the extent
      of bacteremia. Analysis of sera from mice surviving acute infection revealed that
      animals produced antibodies against antigens known to be targets of the immune
      response in humans. Taken together, these data show that small volume aerosol
      inoculation of mice results in acute disease, dose-dependent chronic infection,
      and immune responses that correlate with those seen in human infections. 

PMID- 24098564
TI  - The impact of genome-wide supported schizophrenia risk variants in the
      neurogranin gene on brain structure and function.
AB  - The neural mechanisms underlying genetic risk for schizophrenia, a highly
      heritable psychiatric condition, are still under investigation. New schizophrenia
      risk genes discovered through genome-wide association studies (GWAS), such as
      neurogranin (NRGN), can be used to identify these mechanisms. In this study we
      examined the association of two common NRGN risk single nucleotide polymorphisms
      (SNPs) with functional and structural brain-based intermediate phenotypes for
      schizophrenia. We obtained structural, functional MRI and genotype data of 92
      schizophrenia patients and 114 healthy volunteers from the multisite Mind
      Clinical Imaging Consortium study. Two schizophrenia-associated NRGN SNPs
      (rs12807809 and rs12541) were tested for association with working memory-elicited
      dorsolateral prefrontal cortex (DLPFC) activity and surface-wide cortical
      thickness. NRGN rs12541 risk allele homozygotes (TT) displayed increased working
      memory-related activity in several brain regions, including the left DLPFC, left
      insula, left somatosensory cortex and the cingulate cortex, when compared to non
      risk allele carriers. NRGN rs12807809 non-risk allele (C) carriers showed reduced
      cortical gray matter thickness compared to risk allele homozygotes (TT) in an
      area comprising the right pericalcarine gyrus, the right cuneus, and the right
      lingual gyrus. Our study highlights the effects of schizophrenia risk variants in
      the NRGN gene on functional and structural brain-based intermediate phenotypes
      for schizophrenia. These results support recent GWAS findings and further
      implicate NRGN in the pathophysiology of schizophrenia by suggesting that genetic
      NRGN risk variants contribute to subtle changes in neural functioning and anatomy
      that can be quantified with neuroimaging methods. 

PMID- 24098565
TI  - Gray and white matter distribution in dyslexia: a VBM study of superior temporal
      gyrus asymmetry.
AB  - In the present study, we investigated brain morphological signatures of dyslexia
      by using a voxel-based asymmetry analysis. Dyslexia is a developmental disorder
      that affects the acquisition of reading and spelling abilities and is associated
      with a phonological deficit. Speech perception disabilities have been associated
      with this deficit, particularly when listening conditions are challenging, such
      as in noisy environments. These deficits are associated with known
      neurophysiological correlates, such as a reduction in the functional activation
      or a modification of functional asymmetry in the cortical regions involved in
      speech processing, such as the bilateral superior temporal areas. These
      functional deficits have been associated with macroscopic morphological
      abnormalities, which potentially include a reduction in gray and white matter
      volumes, combined with modifications of the leftward asymmetry along the
      perisylvian areas. The purpose of this study was to investigate gray/white matter
      distribution asymmetries in dyslexic adults using automated image processing
      derived from the voxel-based morphometry technique. Correlations with speech-in
      noise perception abilities were also investigated. The results confirmed the
      presence of gray matter distribution abnormalities in the superior temporal gyrus
      (STG) and the superior temporal Sulcus (STS) in individuals with dyslexia.
      Specifically, the gray matter of adults with dyslexia was symmetrically
      distributed over one particular region of the STS, the temporal voice area,
      whereas normal readers showed a clear rightward gray matter asymmetry in this
      area. We also identified a region in the left posterior STG in which the white
      matter distribution asymmetry was correlated to speech-in-noise comprehension
      abilities in dyslexic adults. These results provide further information
      concerning the morphological alterations observed in dyslexia, revealing the
      presence of both gray and white matter distribution anomalies and the potential
      involvement of these defects in speech-in-noise deficits. 

PMID- 24098566
TI  - The relationship between anxiety and the social judgements of approachability and
      trustworthiness.
AB  - The aim of the current study was to examine the relationship between individual
      differences in anxiety and the social judgements of trustworthiness and
      approachability. We assessed levels of state and trait anxiety in eighty-two
      participants who rated the trustworthiness and approachability of a series of
      unexpressive faces. Higher levels of trait anxiety (controlling for age, sex and
      state anxiety) were associated with the judgement of faces as less trustworthy.
      In contrast, there was no significant association between trait anxiety and
      judgements of approachability. These findings indicate that trait anxiety is a
      significant predictor of trustworthiness evaluations and illustrate the
      importance of considering the role of individual differences in the evaluation of
      trustworthiness. We propose that trait anxiety may be an important variable to
      control for in future studies assessing the cognitive and neural mechanisms
      underlying trustworthiness. This is likely to be particularly important for
      studies involving clinical populations who often experience atypical levels of
      anxiety. 

PMID- 24098567
TI  - Tn6188 - a novel transposon in Listeria monocytogenes responsible for tolerance
      to benzalkonium chloride.
AB  - Controlling the food-borne pathogen Listeria (L.) monocytogenes is of great
      importance from a food safety perspective, and thus for human health. The
      consequences of failures in this regard have been exemplified by recent large
      listeriosis outbreaks in the USA and Europe. It is thus particularly notable that
      tolerance to quaternary ammonium compounds such as benzalkonium chloride (BC) has
      been observed in many L. monocytogenes strains. However, the molecular
      determinants and mechanisms of BC tolerance of L. monocytogenes are still largely
      unknown. Here we describe Tn6188, a novel transposon in L. monocytogenes
      conferring tolerance to BC. Tn6188 is related to Tn554 from Staphylococcus (S.)
      aureus and other Tn554-like transposons such as Tn558, Tn559 and Tn5406 found in
      various Firmicutes. Tn6188 comprises 5117 bp, is integrated chromosomally within
      the radC gene and consists of three transposase genes (tnpABC) as well as genes
      encoding a putative transcriptional regulator and QacH, a small multidrug
      resistance protein family (SMR) transporter putatively associated with export of
      BC that shows high amino acid identity to Smr/QacC from S. aureus and to EmrE
      from Escherichia coli. We screened 91 L. monocytogenes strains for the presence
      of Tn6188 by PCR and found Tn6188 in 10 of the analyzed strains. These isolates
      were from food and food processing environments and predominantly from serovar
      1/2a. L. monocytogenes strains harboring Tn6188 had significantly higher BC
      minimum inhibitory concentrations (MICs) (28.5 +/- 4.7 mg/l) than strains without
      Tn6188 (14 +/- 3.2 mg/l). Using quantitative reverse transcriptase PCR we could
      show a significant increase in qacH expression in the presence of BC. QacH
      deletion mutants were generated in two L. monocytogenes strains and growth
      analysis revealed that DeltaqacH strains had lower BC MICs than wildtype strains.
      In conclusion, our results provide evidence that Tn6188 is responsible for BC
      tolerance in various L. monocytogenes strains. 

PMID- 24098568
TI  - CYLD deubiquitinates RIP1 in the TNFalpha-induced necrosome to facilitate kinase
      activation and programmed necrosis.
AB  - BACKGROUND: Necroptosis/programmed necrosis is initiated by a macro-molecular
      protein complex termed the necrosome. Receptor interacting protein kinase 1
      (RIPK1/RIP1) and RIP3 are key components of the necrosome. TNFalpha is a
      prototypic inducer of necrosome activation, and it is widely believed that
      deubiquitination of RIP1 at the TNFR-1 signaling complex precedes transition of
      RIP1 into the cytosol where it forms the RIP1-RIP3 necrosome. Cylindromatosis
      (CYLD) is believed to promote programmed necrosis by facilitating RIP1
      deubiquitination at this membrane receptor complex. METHODOLOGY/PRINCIPAL
      FINDINGS: We demonstrate that RIP1 is indeed the primary target of CYLD in
      TNFalpha-induced programmed necrosis. We observed that CYLD does not regulate
      RIP1 ubiquitination at the TNF receptor. TNF and zVAD-induced programmed necrosis
      was highly attenuated in CYLD(-/-) cells. However, in the presence of
      cycloheximide or SMAC mimetics, programmed necrosis was only moderately reduced
      in CYLD(-/-) cells. Under the latter conditions, RIP1-RIP3 necrosome formation is
      only delayed, but not abolished in CYLD(-/-) cells. We further demonstrate that
      RIP1 within the NP-40 insoluble necrosome is ubiquitinated and that CYLD
      regulates RIP1 ubiquitination in this compartment. Hence, RIP1 ubiquitination in
      this late-forming complex is greatly increased in CYLD(-/-) cells. Increased RIP1
      ubiquitination impairs RIP1 and RIP3 phosphorylation, a signature of kinase
      activation. CONCLUSIONS/SIGNIFICANCE: Our results show that CYLD regulates RIP1
      ubiquitination in the TNFalpha-induced necrosome, but not in the TNFR-1 signaling
      complex. In cells sensitized to programmed necrosis with SMAC mimetics, CYLD is
      not essential for necrosome assembly. Since SMAC mimetics induces the loss of the
      E3 ligases cIAP1 and cIAP2, reduced RIP1 ubiquitination could lead to reduced
      requirement for CYLD to remove ubiquitin chains from RIP1 in the TNFR-1 complex.
      As increased RIP1 ubiquitination in the necrosome correlates with impaired RIP1
      and RIP3 phosphorylation and function, these results suggest that CYLD controls
      RIP1 kinase activity during necrosome assembly.

PMID- 24098569
TI  - Neural representation of ambiguous visual objects in the inferior temporal
      cortex.
AB  - Inferior temporal (IT) cortex as the final stage of the ventral visual pathway is
      involved in visual object recognition. In our everyday life we need to recognize
      visual objects that are degraded by noise. Psychophysical studies have shown that
      the accuracy and speed of the object recognition decreases as the amount of
      visual noise increases. However, the neural representation of ambiguous visual
      objects and the underlying neural mechanisms of such changes in the behavior are
      not known. Here, by recording the neuronal spiking activity of macaque monkeys'
      IT we explored the relationship between stimulus ambiguity and the IT neural
      activity. We found smaller amplitude, later onset, earlier offset and shorter
      duration of the response as visual ambiguity increased. All of these modulations
      were gradual and correlated with the level of stimulus ambiguity. We found that
      while category selectivity of IT neurons decreased with noise, it was preserved
      for a large extent of visual ambiguity. This noise tolerance for category
      selectivity in IT was lost at 60% noise level. Interestingly, while the response
      of the IT neurons to visual stimuli at 60% noise level was significantly larger
      than their baseline activity and full (100%) noise, it was not category selective
      anymore. The latter finding shows a neural representation that signals the
      presence of visual stimulus without signaling what it is. In general these
      findings, in the context of a drift diffusion model, explain the neural
      mechanisms of perceptual accuracy and speed changes in the process of recognizing
      ambiguous objects. 

PMID- 24098570
TI  - Application of genotyping-by-sequencing on semiconductor sequencing platforms: a
      comparison of genetic and reference-based marker ordering in barley.
AB  - The rapid development of next-generation sequencing platforms has enabled the use
      of sequencing for routine genotyping across a range of genetics studies and
      breeding applications. Genotyping-by-sequencing (GBS), a low-cost, reduced
      representation sequencing method, is becoming a common approach for whole-genome
      marker profiling in many species. With quickly developing sequencing
      technologies, adapting current GBS methodologies to new platforms will leverage
      these advancements for future studies. To test new semiconductor sequencing
      platforms for GBS, we genotyped a barley recombinant inbred line (RIL)
      population. Based on a previous GBS approach, we designed bar code and adapter
      sets for the Ion Torrent platforms. Four sets of 24-plex libraries were
      constructed consisting of 94 RILs and the two parents and sequenced on two Ion
      platforms. In parallel, a 96-plex library of the same RILs was sequenced on the
      Illumina HiSeq 2000. We applied two different computational pipelines to analyze
      sequencing data; the reference-independent TASSEL pipeline and a reference-based
      pipeline using SAMtools. Sequence contigs positioned on the integrated physical
      and genetic map were used for read mapping and variant calling. We found high
      agreement in genotype calls between the different platforms and high concordance
      between genetic and reference-based marker order. There was, however, paucity in
      the number of SNP that were jointly discovered by the different pipelines
      indicating a strong effect of alignment and filtering parameters on SNP
      discovery. We show the utility of the current barley genome assembly as a
      framework for developing very low-cost genetic maps, facilitating high resolution
      genetic mapping and negating the need for developing de novo genetic maps for
      future studies in barley. Through demonstration of GBS on semiconductor
      sequencing platforms, we conclude that the GBS approach is amenable to a range of
      platforms and can easily be modified as new sequencing technologies, analysis
      tools and genomic resources develop. 

PMID- 24098571
TI  - Simulation of platelet, thrombus and erythrocyte hydrodynamic interactions in a
      3D arteriole with in vivo comparison.
AB  - Cylindrical blood vessels, ellipsoid platelets and biconcave-shaped deformable
      erythrocytes (RBCs) are important participants in hemostasis and thrombosis.
      However, due to the challenge of combining these components in simulation tools,
      few simulation studies have included all of them in realistic three-dimensional
      models. In the present study, we apply a recently developed simulation model to
      incorporate these components and analyze the flow in a thrombotic tubular
      arteriole, particularly the detailed hydrodynamic interactions between the
      thrombus shape, RBCs and platelets. It was found that at certain azimuth
      positions, the velocity drops in the proximity of both the upstream and
      downstream edge of the thrombus, which is accompanied by a rapid velocity
      increase in the narrowed region. The RBCs alter the flow profiles significantly
      from the typical low Reynolds (Re) number flow, and also enhance the deposition
      of free flowing platelets onto the thrombus. By evaluating the platelet-thrombus
      interaction and platelet-RBC interaction together, several mechanisms of platelet
      deposition augmentation are identified. With in vivo data comparison, our model
      illustrates the potential of future thrombosis studies that incorporate detailed
      receptor-ligand adhesion modules. 

PMID- 24098572
TI  - Lactobacilli and bifidobacteria promote immune homeostasis by modulating innate
      immune responses to human rotavirus in neonatal gnotobiotic pigs.
AB  - The effects of co-colonization with Lactobacillus rhamnosus GG (LGG) and
      Bifidobacterium lactis Bb12 (Bb12) on 3-dose vaccination with attenuated HRV and
      challenge with virulent human rotavirus (VirHRV) were assessed in 4 groups of
      gnotobiotic (Gn) pigs: Pro+Vac (probiotic-colonized/vaccinated), Vac
      (vaccinated), Pro (probiotic-colonized, non-vaccinated) and Control (non
      colonized, non-vaccinated). Subsets of pigs were euthanized pre- [post-challenge
      day (PCD) 0] and post (PCD7)-VirHRV challenge to assess diarrhea, fecal HRV
      shedding and dendritic cell/innate immune responses. Post-challenge, Pro+Vac and
      Vac groups were completely protected from diarrhea; protection rates against HRV
      shedding were 100% and 83%, respectively. Diarrhea and HRV shedding were reduced
      in Pro compared to Control pigs following VirHRV challenge. Diarrhea scores and
      virus shedding were significantly higher in Controls, compared to all other
      groups, coincident with significantly higher serum interferon-alpha levels post
      challenge. LGG+Bb12 colonization +/-vaccine promoted immunomaturation as
      reflected by increased frequencies of CD4, SWC3a, CD11R1, MHCII expressing
      mononuclear cells (MNCs) and conventional dendritic cells in intestinal tissues
      and blood post-challenge. Colonization decreased frequencies of toll-like
      receptors (TLR) 2 and TLR4 expressing MNCs from vaccinated pigs (Pro+Vac) pre
      challenge and increased frequencies of TLR3 expressing MNCs from Pro pigs post
      challenge, suggesting that probiotics likely exert anti-inflammatory (TLR2 and 4
      down-regulation) and antiviral (TLR3 up-regulation by HRV dsRNA) actions via TLR
      signaling. Probiotic colonization alone (Pro) increased frequencies of intestinal
      and systemic apoptotic MNCs pre-challenge, thereby regulating immune
      hyperreactivity and tolerance. However, these frequencies were decreased in
      intestinal and systemic tissues post-challenge, moderating HRV-induced apoptosis.
      Additionally, post-challenge, Pro+Vac and Pro groups had significantly decreased
      MNC proliferation, suggesting that probiotics control excessive
      lymphoproliferative reactions upon VirHRV challenge. We conclude that in the
      neonatal Gn pig disease model, selected probiotics contribute to
      immunomaturation, regulate immune homeostasis and modulate vaccine and virulent
      HRV effects, thereby moderating HRV diarrhea. 

PMID- 24098574
TI  - Effect of hypohydration on peripheral and corticospinal excitability and
      voluntary activation.
AB  - We investigated whether altered peripheral and/or corticospinal excitatory output
      and voluntary activation are implicated in hypohydration-induced reductions in
      muscle isometric and isokinetic (90 degrees .s(-1)) strength. Nine male athletes
      completed two trials (hypohydrated, euhydrated) comprising 90 min cycling at 40
      degrees C, with body weight losses replaced in euhydrated trial. Peripheral nerve
      and transcranial magnetic stimulations were applied during voluntary contractions
      pre- and 40 min post-exercise to quantify voluntary activation and peripheral (M
      wave) and corticospinal (motor evoked potential) evoked responses in m. vastus
      medialis. Both maximum isometric (-15.3+/-3.1 vs -5.4+/-3.5%) and isokinetic
      eccentric (-24.8+/-4.6 vs -7.3+/-7.2%) torque decreased to a greater extent in
      hypohydrated than euhydrated trials (p<0.05). Half relaxation time of the twitch
      evoked by peripheral nerve stimulation during maximal contractions increased
      after exercise in the hypohydrated (21.8+/-9.3%) but stayed constant in the
      euhydrated (1.6+/-10.7%; p = 0.017) condition. M-wave amplitude during maximum
      voluntary contraction increased after exercise in the heat in hypohydrated
      (10.7+/-18.0%) but decreased in euhydrated condition (-17.4+/-16.9%; p = 0.067).
      Neither peripheral nor cortical voluntary activation were significantly different
      between conditions. Motor evoked potential amplitude increased similarly in both
      conditions (hypohydrated: 25.7+/-28.5%; euhydrated: 52.9+/-33.5%) and was
      accompanied by lengthening of the cortical silent period in euhydrated but not
      hypohydrated condition (p = 0.019). Different neural strategies seem to be
      adopted to regulate neural drive in the two conditions, with increases in
      inhibitory input of either intracortical or corticospinal origin during the
      euhydrated trial. Such changes were absent in the hypohydrated condition, yet
      voluntary activation was similar to the euhydrated condition, perhaps due to
      smaller increases in excitatory drive rather than increased inhibition. Despite
      this maximal isometric and eccentric strength were impaired in the hypohydrated
      condition. The increase in peripheral muscle excitability evident in the
      hypohydrated condition was not sufficient to preserve performance in the face of
      reduced muscle contractility or impaired excitation-contraction coupling. 

PMID- 24098573
TI  - An antimicrobial peptidomimetic induces Mucorales cell death through mitochondria
      mediated apoptosis.
AB  - The incidence of mucormycosis has dramatically increased in immunocompromised
      patients. Moreover, the array of cellular targets whose inhibition results in
      fungal cell death is rather limited. Mitochondria have been mechanistically
      identified as central regulators of detoxification and virulence in fungi. Our
      group has previously designed and developed a proteolytically-resistant
      peptidomimetic motif D(KLAKLAK)2 with pleiotropic action ranging from targeted
      (i.e., ligand-directed) activity against cancer and obesity to non-targeted
      activity against antibiotic resistant gram-negative rods. Here we evaluated
      whether this non-targeted peptidomimetic motif is active against Mucorales. We
      show that D(KLAKLAK)2 has marked fungicidal action, inhibits germination, and
      reduces hyphal viability. We have also observed cellular changes characteristic
      of apoptosis in D(KLAKLAK)2-treated Mucorales cells. Moreover, the fungicidal
      activity was directly correlated with vacuolar injury, mitochondrial swelling and
      mitochondrial membrane depolarization, intracellular reactive oxygen species
      accumulation (ROS), and increased caspase-like enzymatic activity. Finally, these
      apoptotic features were prevented by the addition of the ROS scavenger N-acetyl
      cysteine indicating mechanistic pathway specificity. Together, these findings
      indicate that D(KLAKLAK)2 makes Mucorales exquisitely susceptible via
      mitochondrial injury-induced apoptosis. This prototype may serve as a candidate
      drug for the development of translational applications against mucormycosis and
      perhaps other fungal infections. 

PMID- 24098575
TI  - Processing Chinese relative clauses: evidence for the subject-relative advantage.
AB  - A general fact about language is that subject relative clauses are easier to
      process than object relative clauses. Recently, several self-paced reading
      studies have presented surprising evidence that object relatives in Chinese are
      easier to process than subject relatives. We carried out three self-paced reading
      experiments that attempted to replicate these results. Two of our three studies
      found a subject-relative preference, and the third study found an object-relative
      advantage. Using a random effects bayesian meta-analysis of fifteen studies
      (including our own), we show that the overall current evidence for the subject
      relative advantage is quite strong (approximate posterior probability of a
      subject-relative advantage given the data: 78-80%). We argue that
      retrieval/integration based accounts would have difficulty explaining all three
      experimental results. These findings are important because they narrow the
      theoretical space by limiting the role of an important class of explanation
      retrieval/integration cost-at least for relative clause processing in Chinese. 

PMID- 24098576
TI  - A novel M2e based flu vaccine formulation for dogs.
AB  - BACKGROUND: The USA 2004 influenza virus outbreak H3N8 in dogs heralded the
      emergence of a new disease in this species. A new inactivated H3N8 vaccine was
      developed to control the spread of the disease but, as in humans and swine, it is
      anticipated that the virus will mutate shift and drift in the dog population.
      Therefore, there is a need for a vaccine that can trigger a broad protection to
      prevent the spread of the virus and the emergence of new strains. METHODOLOGY AND
      PRINCIPAL FINDINGS: The universal M2e peptide is identical in almost all the H3N8
      influenza strains sequenced to date and known to infect dogs. This epitope is
      therefore a good choice for development of a vaccine to provide broad protection.
      Malva mosaic virus (MaMV) nanoparticles were chosen as a vaccine platform to
      improve the stability of the M2e peptide and increase its immunogenicity in
      animals. The addition of an adjuvant (OmpC) purified from Salmonella typhi
      membrane in the vaccine formulation increased the immune response directed to the
      M2e peptide significantly and enlarged the protection to include the
      heterosubtypic strain of influenza in a mouse model. An optimal vaccine
      formulation was also shown to be immunogenic in dogs. CONCLUSIONS AND
      SIGNIFICANCE: The MaMV vaccine platform triggered an improved immune response
      directed towards the universal M2e peptide. The adjuvant OmpC increased the
      immune response to the M2e peptide and protection to a heterosubtypic influenza
      strain that harbors a different M2e peptide in a mouse model. Antibodies
      generated by the vaccine formulation showed cross-reactivity with M2e peptides
      derived from influenza strains H9N2, H5N1 and H1N1. The vaccine formulation shows
      a potential for commercialization of a new M2e based vaccine in dogs.

PMID- 24098577
TI  - Cardiac autonomic modulation is determined by gender and is independent of
      aerobic physical capacity in healthy subjects.
AB  - BACKGROUND: Aerobic physical capacity plays an important role in reducing
      morbidity and mortality rates in subjects with cardiovascular diseases. This
      action is often related to an improvement in the autonomic modulation of heart
      rate variability (HRV). However, controversies remain regarding the effects of
      physical training on cardiac autonomic control in healthy subjects. Therefore,
      our objective was to investigate whether aerobic capacity interferes with the
      autonomic modulation of HRV and whether gender differences exist. METHODS:
      Healthy men and women (N=96) were divided into groups according to aerobic
      capacity: low (VO2: 22-38 ml/kg(-1) min(-1)), moderate (VO2: 38-48 ml/kg(-1) min(
      1)) and high (VO2 >48 ml/kg(-1) min(-1).) We evaluated the hemodynamic parameters
      and body composition. The autonomic modulation of HRV was investigated using
      spectral analysis. This procedure decomposes the heart rate oscillatory signal
      into frequency bands: low frequency (LF=0.04-0.15Hz) is mainly related to
      sympathetic modulation, and high frequency (HF=0.15-0.5Hz) corresponds to vagal
      modulation. RESULTS: Aerobic capacity, regardless of gender, determined lower
      values of body fat percentage, blood pressure and heart rate. In turn, the
      spectral analysis of HRV showed that this parameter did not differ when aerobic
      capacity was considered. However, when the genders were compared, women had lower
      LF values and higher HF values than the respective groups of men. CONCLUSION: The
      results suggest that aerobic physical capacity does not interfere with HRV
      modulation; however, the cardiac modulatory balance differs between genders and
      is characterized by a greater influence of the autonomic vagal component in women
      and by the sympathetic component in men.

PMID- 24098578
TI  - Heat shock protein 90: role in enterovirus 71 entry and assembly and potential
      target for therapy.
AB  - Although several factors participating in enterovirus 71 (EV71) entry and
      replication had been reported, the precise mechanisms associated with these
      events are far from clear. In the present study, we showed that heat shock
      protein 90 (HSP90) is a key element associated with EV71 entry and replication in
      a human rhabdomyosarcoma of RD cells. Inhibition of HSP90 by pretreating host
      cells with HSP90beta siRNA or blocking HSP90 with a HSP90-specific antibody or
      geldanamycin (GA), a specific inhibitor of HSP90, as well as recombinant
      HSP90beta resulted in inhibiting viral entry and subsequent viral replication. Co
      immunprecipitation of EV71 with recombinant HSP90beta and colocalization of EV71
      HSP90 in the cells demonstrated that HSP90 was physically associated with EV71
      particles. HSP90 seems to mediate EV71 replication by preventing proteosomal
      degradation of the newly synthesized capsid proteins, but does not facilitate
      viral gene expression at transcriptional level. This was evident by post
      treatment of host cells with GA, which did not affect the expression of viral
      transcripts but accelerated the degradation of viral capsid proteins and
      interfered with the formation of assembled virions. In vivo studies were carried
      out using human SCARB2-transgenic mice to evaluate the protection conferred by
      HSP90 inhibitor, 17-allyamino-17-demethoxygeldanamycin (17-AAG), an analog of
      geldanamycin, that elicited similar activity but with less toxicity. The results
      showed that the administration of 17-AAG twice conferred the resistance to
      hSCARB2 mice challenged with C2, C4, and B4 genotypes of EV71. Our data supports
      HSP90 plays an important role in EV71 infection. Targeting of HSP90 with
      clinically available drugs might provide a feasible therapeutic approach to treat
      EV71 infection. 

PMID- 24098579
TI  - Radiolabeling human peripheral blood stem cells for positron emission tomography
      (PET) imaging in young rhesus monkeys.
AB  - These studies focused on a new radiolabeling technique with copper ((64)Cu) and
      zirconium ((89)Zr) for positron emission tomography (PET) imaging using a CD45
      antibody. Synthesis of (64)Cu-CD45 and (89)Zr-CD45 immunoconjugates was performed
      and the evaluation of the potential toxicity of radiolabeling human peripheral
      blood stem cells (hPBSC) was assessed in vitro (viability, population doubling
      times, colony forming units). hPBSC viability was maintained as the dose of
      (64)Cu-TETA-CD45 increased from 0 (92%) to 160 uCi/mL (76%, p>0.05).
      Radiolabeling efficiency was not significantly increased with concentrations of
      (64)Cu-TETA-CD45 >20 uCi/mL (p>0.50). Toxicity affecting both growth and colony
      formation was observed with hPBSC radiolabeled with >=40 uCi/mL (p<0.05). For
      (89)Zr, there were no significant differences in viability (p>0.05), and a trend
      towards increased radiolabeling efficiency was noted as the dose of (89)Zr-Df
      CD45 increased, with a greater level of radiolabeling with 160 uCi/mL compared to
      0-40 uCi/mL (p<0.05). A greater than 2,000 fold-increase in the level of (89)Zr
      Df-CD45 labeling efficiency was observed when compared to (64)Cu-TETA-CD45.
      Similar to (64)Cu-TETA-CD45, toxicity was noted when hPBSC were radiolabeled with
      >=40 uCi/mL (p<0.05) (growth, colony formation). Taken together, 20 uCi/mL
      resulted in the highest level of radiolabeling efficiency without altering cell
      function. Young rhesus monkeys that had been transplanted prenatally with
      25*10(6) hPBSC expressing firefly luciferase were assessed with bioluminescence
      imaging (BLI), then 0.3 mCi of (89)Zr-Df-CD45, which showed the best
      radiolabeling efficiency, was injected intravenously for PET imaging. Results
      suggest that (89)Zr-Df-CD45 was able to identify engrafted hPBSC in the same
      locations identified by BLI, although the background was high. 

PMID- 24098580
TI  - Alternative 5' untranslated regions are involved in expression regulation of
      human heme oxygenase-1.
AB  - The single nucleotide polymorphism rs2071746 and a (GT)n microsatellite within
      the human gene encoding heme oxygenase-1 (HMOX1) are associated with incidence or
      outcome in a variety of diseases. Most of these associations involve either
      release of heme or oxidative stress. Both polymorphisms are localized in the
      promoter region, but previously reported correlations with heme oxygenase-1
      expression remain not coherent. This ambiguity suggests a more complex
      organization of the 5' gene region which we sought to investigate more fully. We
      evaluated the 5' end of HMOX1 and found a novel first exon 1a placing the two
      previously reported polymorphisms in intronic or exonic positions within the 5'
      untranslated region respectively. Expression of exon 1a can be induced in HepG2
      hepatoma cells by hemin and is a repressor of heme oxygenase-1 translation as
      shown by luciferase reporter assays. Moreover, minigene approaches revealed that
      the quantitative outcome of alternative splicing within the 5' untranslated
      region is affected by the (GT)n microsatellite. This data supporting an extended
      HMOX1 gene model and provide further insights into expression regulation of heme
      oxygenase-1. Alternative splicing within the HMOX1 5' untranslated region
      contributes to translational regulation and is a mechanistic feature involved in
      the interplay between genetic variations, heme oxygenase-1 expression and disease
      outcome. 

PMID- 24098581
TI  - Reinnervation of bilateral posterior cricoarytenoid muscles using the left
      phrenic nerve in patients with bilateral vocal fold paralysis.
AB  - OBJECTIVE: To evaluate the feasibility, effectiveness, and safety of
      reinnervation of the bilateral posterior cricoarytenoid (PCA) muscles using the
      left phrenic nerve in patients with bilateral vocal fold paralysis. METHODS:
      Forty-four patients with bilateral vocal fold paralysis who underwent
      reinnervation of the bilateral PCA muscles using the left phrenic nerve were
      enrolled in this study. Videostroboscopy, perceptual evaluation, acoustic
      analysis, maximum phonation time, pulmonary function testing, and laryngeal
      electromyography were performed preoperatively and postoperatively. Patients were
      followed-up for at least 1 year after surgery. RESULTS: Videostroboscopy showed
      that within 1 year after reinnervation, abductive movement could be observed in
      the left vocal folds of 87% of patients and the right vocal folds of 72% of
      patients. Abductive excursion on the left side was significantly larger than that
      on the right side (P < 0.05); most of the vocal function parameters were improved
      postoperatively compared with the preoperative parameters, albeit without a
      significant difference (P > 0.05). No patients developed immediate dyspnea after
      surgery, and the pulmonary function parameters recovered to normal reference
      value levels within 1 year. Postoperative laryngeal electromyography confirmed
      successful reinnervation of the bilateral PCA muscles. Eighty-seven percent of
      patients in this series were decannulated and did not show obvious dyspnea after
      physical activity. Those who were decannulated after subsequent arytenoidectomy
      were not included in calculating the success rate of decannulation. CONCLUSIONS:
      Reinnervation of the bilateral PCA muscles using the left phrenic nerve can
      restore inspiratory vocal fold abduction to a physiologically satisfactory extent
      while preserving phonatory function at the preoperative level without evident
      morbidity.

PMID- 24098582
TI  - TRPV1 potentiates TGFbeta-induction of corneal myofibroblast development through
      an oxidative stress-mediated p38-SMAD2 signaling loop.
AB  - Injuring mouse corneas with alkali causes myofibroblast expression leading to
      tissue opacification. However, in transient receptor potential vanilloid 1
      channel (TRPV1-/-) knockout mice healing results in transparency restoration.
      Since TGFbeta is the primary inducer of the myofibroblast phenotype, we examined
      the mechanism by which TRPV1 affects TGFbeta-induced myofibroblast development.
      Experiments were performed in pig corneas and human corneal fibroblasts (HCFs).
      Immunohistochemical staining of alpha-smooth muscle actin (alpha-SMA) stress
      fibers was used to visualize myofibroblasts. Protein and phosphoprotein were
      determined by Western blotting. siRNA transfection silenced TRPV1 gene
      expression. Flow cytometry with a reactive oxygen species (ROS) reporting dye
      analyzed intracellular ROS. [Ca2+]I was measured by loading HCF with fura2. In
      organ cultured corneas, the TRPV1 antagonist capsazepine drastically reduced by
      75% wound-induced myofibroblast development. In HCF cell culture, TGF-beta1
      elicited rapid increases in Ca2+ influx, phosphorylation of SMAD2 and MAPKs
      (ERK1/2, JNK1/2 and p38), ROS generation and, after 72 hrs myofibroblast
      development. SMAD2 and p38 activation continued for more than 16 h, whereas p
      ERK1/2 and p-JNK1/2 waned within 90 min. The long-lived SMAD2 activation was
      dependent on activated p38 and vice versa, and it was essential to generate a >
      13-fold increase in alpha-SMA protein and a fully developed myofibroblast
      phenotype. These later changes were markedly reduced by inhibition of TRPV1 or
      reduction of the ROS generation rate. Taken together our results indicate that in
      corneal derived fibroblasts, TGFbeta- induced myofibroblast development is highly
      dependent on a positive feedback loop where p-SMAD2-induced ROS activates TRPV1,
      TRPV1 causes activation of p38, the latter in turn further enhances the
      activation of SMAD2 to establish a recurrent loop that greatly extends the
      residency of the activated state of SMAD2 that drives myofibroblast development. 

PMID- 24098583
TI  - The contribution of non-conventional T cells and NK cells in the mycobacterial
      specific IFNgamma response in Bacille Calmette-Guerin (BCG)-immunized infants.
AB  - BACKGROUND: The Mycobacterium bovis Bacille Calmette-Guerin (BCG) vaccine is
      given to >120 million infants each year worldwide. Most studies investigating the
      immune response to BCG have focused on adaptive immunity. However the importance
      of TCR-gamma/delta (gammadelta) T cells and NK cells in the mycobacterial
      specific immune response is of increasing interest. METHODS: Participants in four
      age-groups were BCG-immunized. Ten weeks later, in vitro BCG-stimulated blood was
      analyzed for NK and T cell markers, and intracellular IFNgamma (IFNgamma) by flow
      cytometry. Total functional IFNgamma response was calculated using integrated
      median fluorescence intensity (iMFI). RESULTS: In infants and children, CD4 and
      CD4-CD8- (double-negative (DN)) T cells were the main IFNgamma-expressing cells
      representing 43-56% and 27-37% of total CD3+ IFNgamma+ T cells respectively. The
      iMFI was higher in DN T cells compared to CD4 T cells in all age groups, with the
      greatest differences seen in infants immunized at birth (p=0.002) or 2 months of
      age (p<0.0001). When NK cells were included in the analysis, they accounted for
      the majority of total IFNgamma-expressing cells and, together with DN Vdelta2
      gammadelta T cells, had the highest iMFI in infants immunized at birth or 2
      months of age. CONCLUSION: In addition to CD4 T cells, NK cells and DN T cells,
      including Vdelta2 gammadelta T cells, are the key populations producing IFNgamma
      in response to BCG immunization in infants and children. This suggests that
      innate immunity and unconventional T cells play a greater role in the
      mycobacterial immune response than previously recognized and should be considered
      in the design and assessment of novel tuberculosis vaccines.

PMID- 24098584
TI  - The fate of spermatogonial stem cells in the cryptorchid testes of RXFP2
      deficient mice.
AB  - The environmental niche of the spermatogonial stem cell pool is critical to
      ensure the continued generation of the germ cell population. To study the
      consequences of an aberrant testicular environment in cryptorchidism we used a
      mouse model with a deletion of Rxfp2 gene resulting in a high intra-abdominal
      testicular position. Mutant males were infertile with the gross morphology of the
      cryptorchid testis progressively deteriorating with age. Few spermatogonia were
      identifiable in 12 month old cryptorchid testes. Gene expression analysis showed
      no difference between mutant and control testes at postnatal day 10. In three
      month old males a decrease in expression of spermatogonial stem cell (SSC)
      markers Id4, Nanos2, and Ret was shown. The direct counting of ID4+ cells
      supported a significant decrease of SSCs. In contrast, the expression of Plzf, a
      marker for undifferentiated and differentiating spermatogonia was not reduced,
      and the number of PLZF+ cells in the cryptorchid testis was higher in three month
      old testes, but equal to control in six month old mutants. The PLZF+ cells did
      not show a higher rate of apoptosis in cryptorchid testis. The expression of the
      Sertoli cell FGF2 gene required for SSC maintenance was significantly reduced in
      mutant testis. Based on these findings we propose that the deregulation of
      somatic and germ cell genes in the cryptorchid testis, directs the SSCs towards
      the differentiation pathway. This leads to a depletion of the SSC pool and an
      increase in the number of PLZF+ spermatogonial cells, which too, eventually
      decreases with the exhaustion of the stem cell pool. Such a dynamic suggests that
      an early correction of cryptorchidism is critical for the retention of the SSC
      pool. 

PMID- 24098585
TI  - ZAC1 and SSTR2 are downregulated in non-functioning pituitary adenomas but not in
      somatotropinomas.
AB  - INTRODUCTION: There are few data regarding ZAC1 expression in clinically non
      functioning pituitary adenomas (NFPA). Because somatotropinomas and NFPA behave
      differently with respect to tumor shrinkage during somatostatin analogs (SA)
      therapy, we sought to compare the ZAC1 and somatostatin receptor (sstr) types 1,
      2, 3 and 5 mRNA expression in these two pituitary adenoma subtypes and in normal
      human pituitaries. METHODS: ZAC1 and SSTR mRNA expression levels were evaluated
      using real-time RT-PCR (TaqMan) in 20 NFPA and compared with the expression
      levels in 23 somatotropinomas and five normal pituitaries. The NFPA invasiveness
      was evaluated using magnetic resonance imaging with Hardy's modified criteria. Ki
      67 and p53 were evaluated using immunohistochemistry. RESULTS: A total of 20
      patients with NFPA [6 males, median age 56 years (range: 30-78)], 23 with
      acromegaly [12 males, median age 43 years (range: 24-57)] and five normal
      pituitaries [4 males, median age 48 years (range: 36-54)] were included. Four of
      the patients (20%) had Hardy's grade 2 tumors; all of the others had Hardy's
      grade 3 tumors. The Ki-67 median expression was 2.35 (range: 0.2-9.23), and only
      four of the tumors (20%) were positive for p53. The ZAC1 mRNA expression was
      significantly lower in NFPA than in somatotropinomas and in normal pituitaries
      (p<0.001 for both), as well as the SSTR2 (p=0.001 and 0.01, respectively). The
      SSTR3 expression was higher in the NFPA than in the somatotropinomas and in the
      normal pituitaries (p=0.03 and 0.02, respectively). No correlation was found
      between the ZAC1 mRNA expression and the tumor invasiveness, Ki-67 and p53.
      CONCLUSION: ZAC1 and SSTR2 are underexpressed and SSTR3 is overexpressed in NFPA
      compared to those in somatotropinomas and in normal pituitaries, which might
      explain the lack of tumor shrinkage that is observed in response to commercially
      available SA therapy in patients with NFPA.

PMID- 24098586
TI  - Effect of immune reconstitution on the incidence of HIV-related Hodgkin lymphoma.
AB  - BACKGROUND: The incidence of Hodgkin lymphoma (HL) has increased since
      introduction of combined antiretroviral therapy (cART). While HIV-related HL is
      highly associated with EBV, the causes underlying the rising incidence remain
      unclear. The aim of this study was to evaluate the effect of immune
      reconstitution on HL incidence among a cohort of HIV-infected male veterans ever
      receiving cART. METHODS: We performed a retrospective cohort study utilizing data
      from the Veterans Affairs HIV Clinical Case Registry from 1985-2010. HL cases
      were identified using ICD-9 codes (201.4-9). Poisson regression was conducted to
      evaluate relationships between cART-related immunologic measures (e.g., nadir CD4
      before cART, time-updated CD4, % time undetectable HIV RNA) and HL incidence.
      Additionally, we examined CD4 change after cART initiation. RESULTS: 31,056 cART
      users contributed 287,256 person-years and 196 HL cases (IR=6.8/10,000 person
      years). Rate of CD4 increase after cART was worse among HL cases than non-cases
      (p<0.05). In multivariate regression, HL risk was elevated among veterans with
      recent CD4 200-350 cells/uL (IRR=1.67, 95%CI=1.16-2.40) and <200 cells/uL
      (IRR=1.61, 95%CI=1.09-2.39), compared to >350 cells/uL. HL risk was lower among
      veterans with >80% time undetectable HIV RNA (IRR=0.57, 95%CI=0.35-0.92) and 40
      80% undetectable (IRR=0.68, 95%CI=0.47-0.99), compared to <40% undetectable. HL
      risk was higher in the first 12 months (IRR=2.02, 95%CI=1.32-3.10) and 12-24
      months (IRR=1.75, 95%CI=1.16-2.64) after cART initiation, compared to >36 months.
      CONCLUSION: These data highlight immunosuppression and poor viral control may
      increase HL risk, specifically during immune reconstitution in the interval post
      cART initiation. Findings suggest an immune reconstitution type mechanism in HIV
      related HL development.

PMID- 24098587
TI  - The blood neutrophil to lymphocyte ratio correlates with clinical status in
      children with cystic fibrosis: a retrospective study.
AB  - PURPOSE: The blood neutrophil to lymphocyte ratio (NLR) has been identified as a
      potentially useful marker of clinical outcome in disease states with an
      inflammatory component. The objective of this study was to evaluate the
      relationship between NLR and clinical status in children with cystic fibrosis.
      METHODS: This was a retrospective chart review. Data collected included NLR, body
      mass index, and forced expiratory volume in 1 second (FEV1) while asymptomatic,
      and during hospitalizations for pulmonary exacerbation. An NLR breakpoint of 3
      was used for comparisons of body mass index and FEV1. RESULTS: A total of 159
      charts were reviewed. An NLR >= 3 was significantly associated with lower body
      mass index and lower FEV1. NLR during hospitalization was significantly higher
      than NLR while asymptomatic. NLR measured during the first 3 months of life was
      negatively correlated with FEV1 at age 12. CONCLUSION: NLR correlates with
      clinical status in children with cystic fibrosis and may be a useful biomarker in
      this population.

PMID- 24098588
TI  - Slipping through the cracks: the taxonomic impediment conceals the origin and
      dispersal of Haminoea japonica, an invasive species with impacts to human health.
AB  - Haminoea japonica is a species of opisthobranch sea slug native to Japan and
      Korea. Non-native populations have spread unnoticed for decades due to
      difficulties in the taxonomy of Haminoea species. Haminoea japonica is associated
      with a schistosome parasite in San Francisco Bay, thus further spread could have
      consequence to human health and economies. Anecdotal evidence suggests that H.
      japonica has displaced native species of Haminoea in North America and Europe,
      becoming locally dominant in estuaries and coastal lagoons. In this paper we
      study the population genetics of native and non-native populations of H. japonica
      based on mt-DNA data including newly discovered populations in Italy and France.
      The conclusions of this study further corroborate a Northeastern Japan origin for
      the non-native populations and suggest possible independent introductions into
      North America and Europe. Additionally, the data obtained revealed possible
      secondary introductions within Japan. Although non-native populations have
      experienced severe genetic bottlenecks they have colonized different regions with
      a broad range of water temperatures and other environmental conditions. The
      environmental tolerance of this species, along with its ability to become
      dominant in invaded areas and its association with a schistosome parasite,
      suggest H. japonica could be a dangerous invasive species. 

PMID- 24098589
TI  - Faster metabolite (1)H transverse relaxation in the elder human brain.
AB  - (1)H magnetic resonance spectroscopy (MRS) is unique among imaging modalities
      because signals from several metabolites are measured during a single examination
      period. Each metabolite reflects a distinct intracellular process. Furthermore
      transverse (T2 ) relaxation times probe the viability of the cell
      microenvironment, e.g., the viscosity of the cellular fluids, the microscopic
      susceptibility distribution within the cells, and the iron content. In this
      study, T2s of brain metabolites were measured in the occipital lobe of eighteen
      young and fourteen elderly subjects at a field strength of 4 tesla. The T2s of N
      acetylaspartate, total creatine, and total choline were 23%, 16% and 10% shorter
      in elderly than in young subjects. The findings of this study suggest that
      noninvasive detection of T2 provides useful biological information on changes in
      the cellular microenvironment that take place during aging. 

PMID- 24098590
TI  - Population differentiation and species formation in the deep sea: the potential
      role of environmental gradients and depth.
AB  - Ecological speciation probably plays a more prominent role in diversification
      than previously thought, particularly in marine ecosystems where dispersal
      potential is great and where few obvious barriers to gene flow exist. This may be
      especially true in the deep sea where allopatric speciation seems insufficient to
      account for the rich and largely endemic fauna. Ecologically driven population
      differentiation and speciation are likely to be most prevalent along
      environmental gradients, such as those attending changes in depth. We quantified
      patterns of genetic variation along a depth gradient (1600-3800m) in the western
      North Atlantic for a protobranch bivalve (Nuculaatacellana) to test for
      population divergence. Multilocus analyses indicated a sharp discontinuity across
      a narrow depth range, with extremely low gene flow inferred between shallow and
      deep populations for thousands of generations. Phylogeographical discordance
      occurred between nuclear and mitochondrial loci as might be expected during the
      early stages of species formation. Because the geographic distance between
      divergent populations is small and no obvious dispersal barriers exist in this
      region, we suggest the divergence might reflect ecologically driven selection
      mediated by environmental correlates of the depth gradient. As inferred for
      numerous shallow-water species, environmental gradients that parallel changes in
      depth may play a key role in the genesis and adaptive radiation of the deep-water
      fauna. 

PMID- 24098591
TI  - An in vitro model of the horse gut microbiome enables identification of lactate
      utilizing bacteria that differentially respond to starch induction.
AB  - Laminitis is a chronic, crippling disease triggered by the sudden influx of
      dietary starch. Starch reaches the hindgut resulting in enrichment of lactic acid
      bacteria, lactate accumulation, and acidification of the gut contents. Bacterial
      products enter the bloodstream and precipitate systemic inflammation. Hindgut
      lactate levels are normally low because specific bacterial groups convert lactate
      to short chain fatty acids. Why this mechanism fails when lactate levels rapidly
      rise, and why some hindgut communities can recover is unknown. Fecal samples from
      three adult horses eating identical diets provided bacterial communities for this
      in vitro study. Triplicate microcosms of fecal slurries were enriched with
      lactate and/or starch. Metabolic products (short chain fatty acids, headspace
      gases, and hydrogen sulfide) were measured and microbial community compositions
      determined using Illumina 16S rRNA sequencing over 12-hour intervals. We report
      that patterns of change in short chain fatty acid levels and pH in our in vitro
      system are similar to those seen in in vivo laminitis induction models. Community
      differences between microcosms with disparate abilities to clear excess lactate
      suggest profiles conferring resistance of starch-induction conditions. Where
      lactate levels recover following starch induction conditions, propionate and
      acetate levels rise correspondingly and taxa related to Megasphaeraelsdenii reach
      levels exceeding 70% relative abundance. In lactate and control cultures, taxa
      related to Veillonellamontpellierensis are enriched as lactate levels fall.
      Understanding these community differences and factors promoting the growth of
      specific lactate utilizing taxa may be useful to prevent acidosis under starch
      induction conditions. 

PMID- 24098592
TI  - Melanotic pathology and vertical transmission of the gut commensal
      Elizabethkingia meningoseptica in the major malaria vector Anopheles gambiae.
AB  - BACKGROUND: The resident gut flora is known to have significant impacts on the
      life history of the host organism. Endosymbiotic bacterial species in the
      Anopheles mosquito gut are potent modulators of sexual development of the malaria
      parasite, Plasmodium, and thus proposed as potential control agents of malaria
      transmission. RESULTS: Here we report a melanotic pathology in the major African
      malaria vector Anopheles gambiae, caused by the dominant mosquito endosymbiont
      Elizabethkingiameningoseptica. Transfer of melanised tissues into the haemolymph
      of healthy adult mosquitoes or direct haemolymph inoculation with isolated E.
      meningoseptica bacteria were the only means for transmission and de novo
      formation of melanotic lesions, specifically in the fat body tissues of recipient
      individuals. We show that E. meningoseptica can be vertically transmitted from
      eggs to larvae and that E. meningoseptica-mono-associated mosquitoes display
      significant mortality, which is further enhanced upon Plasmodium infection,
      suggesting a synergistic impact of E. meningoseptica and Plasmodium on mosquito
      survival. CONCLUSION: The high pathogenicity and permanent association of E.
      meningoseptica with An. Gambiae through vertical transmission constitute
      attractive characteristics towards the potential design of novel mosquito/malaria
      biocontrol strategies.

PMID- 24098593
TI  - PD-0332991, a CDK4/6 inhibitor, significantly prolongs survival in a genetically
      engineered mouse model of brainstem glioma.
AB  - Diffuse intrinsic pontine glioma (DIPG) is an incurable tumor that arises in the
      brainstem of children. To date there is not a single approved drug to effectively
      treat these tumors and thus novel therapies are desperately needed. Recent
      studies suggest that a significant fraction of these tumors contain alterations
      in cell cycle regulatory genes including amplification of the D-type cyclins and
      CDK4/6, and less commonly, loss of Ink4a-ARF leading to aberrant cell
      proliferation. In this study, we evaluated the therapeutic approach of targeting
      the cyclin-CDK-Retinoblastoma (Rb) pathway in a genetically engineered PDGF-B
      driven brainstem glioma (BSG) mouse model. We found that PD-0332991 (PD), a
      CDK4/6 inhibitor, induces cell-cycle arrest in our PDGF-B; Ink4a-ARF deficient
      model both in vitro and in vivo. By contrast, the PDGF-B; p53 deficient model was
      mostly resistant to treatment with PD. We noted that a 7-day treatment course
      with PD significantly prolonged survival by 12% in the PDGF-B; Ink4a-ARF
      deficient BSG model. Furthermore, a single dose of 10 Gy radiation therapy (RT)
      followed by 7 days of treatment with PD increased the survival by 19% in
      comparison to RT alone. These findings provide the rationale for evaluating PD in
      children with Ink4a-ARF deficient gliomas. 

PMID- 24098594
TI  - Genetically engineered frameshifted YopN-TyeA chimeras influence type III
      secretion system function in Yersinia pseudotuberculosis.
AB  - Type III secretion is a tightly controlled virulence mechanism utilized by many
      gram negative bacteria to colonize their eukaryotic hosts. To infect their host,
      human pathogenic Yersinia spp. translocate protein toxins into the host cell
      cytosol through a preassembled Ysc-Yop type III secretion device. Several of the
      Ysc-Yop components are known for their roles in controlling substrate secretion
      and translocation. Particularly important in this role is the YopN and TyeA
      heterodimer. In this study, we confirm that Y. pseudotuberculosis naturally
      produce a 42 kDa YopN-TyeA hybrid protein as a result of a +1 frame shift near
      the 3 prime of yopN mRNA, as has been previously reported for the closely related
      Y. pestis. To assess the biological role of this YopN-TyeA hybrid in T3SS by Y.
      pseudotuberculosis, we used in cis site-directed mutagenesis to engineer bacteria
      to either produce predominately the YopN-TyeA hybrid by introducing +1 frame
      shifts to yopN after codon 278 or 287, or to produce only singular YopN and TyeA
      polypeptides by introducing yopN sequence from Y. enterocolitica, which is known
      not to produce the hybrid. Significantly, the engineered 42 kDa YopN-TyeA fusions
      were abundantly produced, stable, and were efficiently secreted by bacteria in
      vitro. Moreover, these bacteria could all maintain functionally competent needle
      structures and controlled Yops secretion in vitro. In the presence of host cells
      however, bacteria producing the most genetically altered hybrids (+1 frameshift
      after 278 codon) had diminished control of polarized Yop translocation. This
      corresponded to significant attenuation in competitive survival assays in orally
      infected mice, although not at all to the same extent as Yersinia lacking both
      YopN and TyeA proteins. Based on these studies with engineered polypeptides, most
      likely a naturally occurring YopN-TyeA hybrid protein has the potential to
      influence T3S control and activity when produced during Yersinia-host cell
      contact. 

PMID- 24098595
TI  - Disruption of sarcoendoplasmic reticulum calcium ATPase function in Drosophila
      leads to cardiac dysfunction.
AB  - Abnormal sarcoendoplasmic reticulum Calcium ATPase (SERCA) function has been
      associated with poor cardiac function in humans. While modifiers of SERCA
      function have been identified and studied using animal models, further
      investigation has been limited by the absence of a model system that is amenable
      to large-scale genetic screens. Drosophila melanogaster is an ideal model system
      for the investigation of SERCA function due to the significant homology to human
      SERCA and the availability of versatile genetic screening tools. To further the
      use of Drosophila as a model for examining the role of SERCA in cardiac function,
      we examined cardiac function in adult flies. Using optical coherence tomography
      (OCT) imaging in awake, adult Drosophila, we have been able to characterize
      cardiac chamber dimensions in flies with disrupted in Drosophila SERCA (CaP60A).
      We found that the best studied CaP60A mutant, the conditional paralytic mutant
      CaP60A(kum170), develops marked bradycardia and chamber enlargement that is
      closely linked to the onset of paralysis and dependent on extra cardiac CaP60A.
      In contrast to prior work, we show that disruption of CaP60A in a cardiac
      specific manner results in cardiac dilation and dysfunction rather than
      alteration in heart rate. In addition, the co-expression of a calcium release
      channel mutation with CaP60A (kum170) is sufficient to rescue the cardiac
      phenotype but not paralysis. Finally, we show that CaP60A overexpression is able
      to rescue cardiac function in a model of Drosophila cardiac dysfunction similar
      to what is observed in mammals. Thus, we present a cardiac phenotype associated
      with Drosophila SERCA dysfunction that would serve as additional phenotyping for
      further large-scale genetic screens for novel modifiers of SERCA function. 

PMID- 24098596
TI  - Highly sensitive quantitative real-time PCR for the detection of Plasmodium liver
      stage parasite burden following low-dose sporozoite challenge.
AB  - The pre-erythrocytic stages of Plasmodium spp. are increasingly recognised as
      ideal targets for prophylactic vaccines and drug treatments. Intense research
      efforts in the last decade have been focused on in vitro culture and in vivo
      detection and quantification of liver stage parasites to assess the effects of
      candidate vaccines or drugs. Typically, the onset of blood stage parasitaemia is
      used as a surrogate endpoint to estimate the efficacy of vaccines and drugs
      targeting pre-erythrocytic parasite stages in animal models. However, this
      provides no information on the parasite burden in the liver after vaccination or
      treatment and therefore does not detect partial efficacy of any vaccine or drug
      candidates. Herein, we describe a quantitative RT-PCR method adapted to detect
      and quantitate Plasmodium yoelii liver stages in mice with increased sensitivity
      even after challenge with as few as 50 cryopreserved sporozoites (corresponding
      to approximately 5-10 freshly isolated sporozoites). We have validated our
      quantitative RT-PCR assay according to the MIQE (Minimum Information for
      Publication of Quantitative Real-Time PCR Experiments) guidelines and established
      high reproducibility and accuracy. Our assay provides a rapid and reproducible
      assessment of liver stage parasite burden in rodent malaria models, thereby
      facilitating the evaluation of the efficacy of anti-malarial drugs or
      prophylactic vaccines with high precision and efficacy. 

PMID- 24098598
TI  - Rapid range shift in an introduced tropical marine invertebrate.
AB  - The barnacle Megabalanus coccopoma is native to shorelines from Baja California
      to Peru and has been introduced to a number of other locations including the
      Atlantic US SE coast, where it was first recorded in 2006. In 2009, the range of
      M. coccopoma in the SE US extended from Ft. Pierce, FL north to Cape Hatteras, NC
      with seasonal populations found as far north as Kitty Hawk, NC. During the
      exceptionally cold winter of 2009/2010, the range of M. coccopoma shifted
      dramatically due to the dieback of all monitored populations north of Florida. We
      examined body size, distribution, and density of M. coccopoma during the summers
      of 2010, 2011, and 2012 to describe the extent of the range retraction and the
      rate of range re-expansion. In 2010, recruits were found as far north as Tybee
      Island, Ga, but no established populations were found north of Florida. In 2011
      recruits were found at Rodanthe, NC but established populations were still
      limited to Florida. By 2012 populations were established in Rodanthe, NC,
      slightly north of its previously known range limit. Estimated rates of range re
      expansion were 255.8 km/yr in 2010 and 794.1 km/yr in 2011. Rates of re-expansion
      to the north in 2010 and 2011 were faster than have previously been reported for
      any marine species, and are one of the few rates published for any tropical
      marine invertebrate. 

PMID- 24098597
TI  - Impact of plasmids, including those encodingVirB4/D4 type IV secretion systems,
      on Salmonella enterica serovar Heidelberg virulence in macrophages and epithelial
      cells.
AB  - Salmonella enterica serovar Heidelberg (S. Heidelberg) can cause foodborne
      illness in humans following the consumption of contaminated meat and poultry
      products. Recent studies from our laboratory have demonstrated that certain S.
      Heidelberg isolated from food-animal sources harbor multiple transmissible
      plasmids with genes that encode antimicrobial resistance, virulence and a
      VirB4/D4 type-IV secretion system. This study examines the potential role of
      these transmissible plasmids in bacterial uptake and survival in intestinal
      epithelial cells and macrophages, and the molecular basis of host immune system
      modulation that may be associated with disease progression. A series of
      transconjugant and transformant strains were developed with different
      combinations of the plasmids to determine the roles of the individual and
      combinations of plasmids on virulence. Overall the Salmonella strains containing
      the VirB/D4 T4SS plasmids entered and survived in epithelial cells and
      macrophages to a greater degree than those without the plasmid, even though they
      carried other plasmid types. During entry in macrophages, the VirB/D4 T4SS
      encoding genes are up-regulated in a time-dependent fashion. When the potential
      mechanisms for increased virulence were examined using an antibacterial Response
      PCR Array, the strain containing the T4SS down regulated several host innate
      immune response genes which likely contributed to the increased uptake and
      survival within macrophages and epithelial cells. 

PMID- 24098599
TI  - Inner nuclear layer thickening is inversley proportional to retinal ganglion cell
      loss in optic neuritis.
AB  - AIM: To examine the relationship between retinal ganglion cell loss and changes
      in the inner nuclear layer (INL) in optic neuritis (ON). METHODS: 36 multiple
      sclerosis (MS) patients with a history of ON and 36 age and sex-matched controls
      underwent Optical Coherence Tomography. The paramacular retinal nerve fiber layer
      (RNFL), combined ganglion cell and inner plexiform layers (GCL/IPL) and inner
      nuclear layer (INL) thickness were measured at 36 points around the fovea. To
      remove inter-subject variability, the difference in thickness of each layer
      between the ON and fellow eye of each patient was calculated. A topographic
      analysis was conducted. RESULTS: The INL of the ON patients was thicker than the
      controls (42.9um versus 39.6um, p=0.002). ON patients also had a thinner RNFL
      (27.8um versus 32.2um, p<0.001) and GCL/IPL (69.3um versus 98.1um, p<0.001).
      Among the controls, there was no correlation between RNFL and GCL/IPL as well as
      RNFL and INL, but a positive correlation was seen between GCL/IPL and INL
      (r=0.65, p<0.001). In the ON group, there was a positive correlation between RNFL
      and GCL/IPL (r=0.80, p<0.001) but a negative correlation between RNFL and INL (r=
      0.61, p<0.001) as well as GCL/IPL and INL (r=-0.44, p=0.007). The negative
      correlation between GCL/IPL and INL strengthened in the ON group when inter
      subject variability was removed (r=-0.75, p<0.001). Microcysts within the INL
      were present in 5 ON patients, mainly in the superior and infero-nasal
      paramacular regions. While patients with microcysts lay at the far end of the
      correlation curve between GCL/IPL and INL (i.e. larger INL and smaller GCL/IPL
      compared to other patients), their exclusion did not affect the correlation (r= 
      0.76, p<0.001). CONCLUSIONS: INL enlargement in MS-related ON is associated with
      the severity of GCL loss. This is a continuous relationship and patients with INL
      microcysts may represent the extreme end of the scale.

PMID- 24098628
TI  - Retraction: Small protein-mediated quorum sensing in a gram-negative bacterium.

PMID- 24098629
TI  - Validity and reliability of the Japanese version of the painDETECT questionnaire:
      a multicenter observational study.
AB  - OBJECTIVES: The aim of this study was to evaluate the validity and reliability of
      the Japanese version of the painDETECT questionnaire (PDQ-J). MATERIALS AND
      METHODS: The translation of the original PDQ into Japanese was achieved according
      to the published guidelines. Subsequently, a multicenter observational study was
      performed to evaluate the validity and reliability of PDQ-J, including 113
      Japanese patients suffering from pain. RESULTS: Factor analysis revealed that the
      main component of PDQ-J comprises two determinative factors, which account for
      62% of the variance observed. Moreover, PDQ-J revealed statistically significant
      correlation with the intensity of pain (Numerical Rating Scale), Physical
      Component Score, and Mental Component Score of the Medical Outcomes Study 36-Item
      Short-Form Health Survey (SF-36). The Cronbach alpha for the total score was 0.78
      and for the main component was 0.80. In the analysis of test-retest method, the
      intraclass correlation coefficient between the two scores was 0.94. CONCLUSIONS:
      We demonstrated the validity and reliability of PDQ-J. We encourage researchers
      and clinicians to use this tool for the assessment of patients who suffer
      suspected neuropathic pain.

PMID- 24098600
TI  - Comparative immunogenicity of HIV-1 gp160, gp140 and gp120 expressed by live
      attenuated newcastle disease virus vector.
AB  - The development of a vaccine against human immunodeficiency virus-1 (HIV-1)
      capable of inducing broad humoral and cellular responses at both the systemic and
      mucosal levels will be critical for combating the global AIDS epidemic. We
      previously demonstrated the ability of Newcastle disease virus (NDV) as a vaccine
      vector to express oligomeric Env protein gp160 and induce potent humoral and
      mucosal immune responses. In the present study, we used NDV vaccine strain LaSota
      as a vector to compare the biochemical and immunogenic properties of vector
      expressed gp160, gp120, and two versions of gp140 (a derivative of gp160 made by
      deleting the transmembrane and cytoplasmic domains), namely: gp140L, which
      contained the complete membrane-proximal external region (MPER), and gp140S,
      which lacks the distal half of MPER. We show that, similar to gp160, NDV
      expressed gp140S and gp120, but not gp140L, formed higher-order oligomers that
      retained recognition by conformationally sensitive monoclonal antibodies.
      Immunization of guinea pigs by the intranasal route with rLaSota/gp140S resulted
      in significantly greater systemic and mucosal antibody responses compared to the
      other recombinants. Immunization with rLaSota/140S, rLaSota/140L rLaSota/120
      resulted in mixed Th1/Th2 immune responses as compared to Th1-biased immune
      responses induced by rLaSota/160. Importantly, rLaSota/gp140S induced
      neutralizing antibody responses to homologous HIV-1 strain BaL.26 and laboratory
      adapted HIV-1 strain MN.3 that were stronger than those elicited by the other NDV
      recombinants. Additionally, rLaSota/gp140S induced greater CD4+ and CD8+ T-cell
      responses in mice. These studies illustrate that rLaSota/gp140S is a promising
      vaccine candidate to elicit potent mucosal, humoral and cellular immune responses
      to the HIV-1 Env protein. 

PMID- 24098630
TI  - Internet-based attention bias modification for social anxiety: a randomised
      controlled comparison of training towards negative and training towards positive
      cues.
AB  - Biases in attention processes are thought to play a crucial role in the aetiology
      and maintenance of Social Anxiety Disorder (SAD). The goal of the present study
      was to examine the efficacy of a programme intended to train attention towards
      positive cues and a programme intended to train attention towards negative cues.
      In a randomised, controlled, double-blind design, the impact of these two
      training conditions on both selective attention and social anxiety were compared
      to that of a control training condition. A modified dot probe task was used, and
      delivered via the internet. A total of 129 individuals, diagnosed with SAD, were
      randomly assigned to one of these three conditions and took part in a 14-day
      programme with daily training/control sessions. Participants in all three groups
      did not on average display an attentional bias prior to the training. Critically,
      results on change in attention bias implied that significantly differential
      change in selective attention to threat was not detected in the three conditions.
      However, symptoms of social anxiety reduced significantly from pre- to follow-up
      assessment in all three conditions (dwithin  = 0.63-1.24), with the procedure
      intended to train attention towards threat cues producing, relative to the
      control condition, a significantly greater reduction of social fears. There were
      no significant differences in social anxiety outcome between the training
      condition intended to induce attentional bias towards positive cues and the
      control condition. To our knowledge, this is the first RCT where a condition
      intended to induce attention bias to negative cues yielded greater emotional
      benefits than a control condition. Intriguingly, changes in symptoms are unlikely
      to be by the mechanism of change in attention processes since there was no change
      detected in bias per se. Implications of this finding for future research on
      attention bias modification in social anxiety are discussed. TRIAL REGISTRATION:
      ClinicalTrials.gov NCT01463137.

PMID- 24098631
TI  - Interactive rhythmic cue facilitates gait relearning in patients with Parkinson's
      disease.
AB  - To develop a method for cooperative human gait training, we investigated whether
      interactive rhythmic cues could improve the gait performance of Parkinson's
      disease patients. The interactive rhythmic cues ware generated based on the
      mutual entrainment between the patient's gait rhythms and the cue rhythms input
      to the patient while the patient walked. Previously, we found that the dynamic
      characteristics of stride interval fluctuation in Parkinson's disease patients
      were improved to a healthy 1/f fluctuation level using interactive rhythmic cues
      and that this effect was maintained in the short term. However, two problems
      remained in our previous study. First, it was not clear whether the key factor
      underpinning the effect was the mutual entrainment between the gait rhythms and
      the cue rhythms or the rhythmic cue fluctuation itself. Second, it was not clear
      whether or not the gait restoration was maintained longitudinally and was
      relearned after repeating the cue-based gait training. Thus, the present study
      clarified these issues using 32 patients who participated in a four-day
      experimental program. The patients were assigned randomly to one of four
      experimental groups with the following rhythmic cues: (a) interactive rhythmic
      cue, (b) fixed tempo cue, (c) 1/f fluctuating tempo cue, and (d) no cue. It has
      been reported that the 1/f fluctuation of stride interval in healthy gait is
      absent in Parkinson's disease patients. Therefore, we used this dynamic
      characteristic as an evaluation index to analyze gait relearning in the four
      different conditions. We observed a significant effect in condition (a) that the
      gait fluctuation of the patients gradually returned to a healthy 1/f fluctuation
      level, whereas this did not occur in the other conditions. This result suggests
      that the mutual entrainment can facilitate gait relearning effectively. It is
      expected that interactive rhythmic cues will be widely applicable in the fields
      of rehabilitation and assistive technology. 

PMID- 24098632
TI  - Microbial communities of deep-sea methane seeps at Hikurangi continental margin
      (New Zealand).
AB  - The methane-emitting cold seeps of Hikurangi margin (New Zealand) are among the
      few deep-sea chemosynthetic ecosystems of the Southern Hemisphere known to date.
      Here we compared the biogeochemistry and microbial communities of a variety of
      Hikurangi cold seep ecosystems. These included highly reduced seep habitats
      dominated by bacterial mats, partially oxidized habitats populated by
      heterotrophic ampharetid polychaetes and deeply oxidized habitats dominated by
      chemosynthetic frenulate tubeworms. The ampharetid habitats were characterized by
      a thick oxic sediment layer that hosted a diverse and biomass-rich community of
      aerobic methanotrophic Gammaproteobacteria. These bacteria consumed up to 25% of
      the emanating methane and clustered within three deep-branching groups named
      Marine Methylotrophic Group (MMG) 1-3. MMG1 and MMG2 methylotrophs belong to the
      order Methylococcales, whereas MMG3 methylotrophs are related to the
      Methylophaga. Organisms of the groups MMG1 and MMG3 are close relatives of
      chemosynthetic endosymbionts of marine invertebrates. The anoxic sediment layers
      of all investigated seeps were dominated by anaerobic methanotrophic archaea
      (ANME) of the ANME-2 clade and sulfate-reducing Deltaproteobacteria. Microbial
      community analysis using Automated Ribosomal Intergenic Spacer Analysis (ARISA)
      showed that the different seep habitats hosted distinct microbial communities,
      which were strongly influenced by the seep-associated fauna and the geographic
      location. Despite outstanding features of Hikurangi seep communities, the
      organisms responsible for key ecosystem functions were similar to those found at
      seeps worldwide. This suggests that similar types of biogeochemical settings
      select for similar community composition regardless of geographic distance.
      Because ampharetid polychaetes are widespread at cold seeps the role of aerobic
      methanotrophy may have been underestimated in seafloor methane budgets. 

PMID- 24098633
TI  - A home exercise programme is no more beneficial than advice and education for
      people with neurogenic claudication: results from a randomised controlled trial.
AB  - OBJECTIVE: To compare the effectiveness of a physiotherapy programme with a
      control treatment of advice and education in patients with neurogenic
      claudication symptoms. DESIGN: Pragmatic randomised controlled clinical trial.
      SETTING: Primary care-based musculoskeletal service. PATIENTS: Adults aged 50 or
      over with neurogenic claudication symptoms causing limitation of walking.
      INTERVENTIONS: Condition-specific home exercises combined with advice and
      education, or advice and education alone. MAIN OUTCOME MEASURES: The primary
      outcome was the difference in improvement of symptom severity scores on the Swiss
      Spinal Stenosis Scale at eight weeks. Secondary outcomes included measures of
      physical function, pain and general well-being at eight weeks and 12 months.
      RESULTS: There was no significant difference between groups in the Swiss Spinal
      Stenosis symptom severity scale at eight weeks (t = 0.47, p = 0.643): mean change
      (SD) control group -0.18 (0.47), treatment group -0.10 (0.66), difference (95%
      CI) 0.08 (-0.19, 0.35); baseline-adjusted difference 0.06 (-0.19, 0.31)]. An
      unplanned subgroup analysis suggested that for patients with the top 25% of
      baseline symptom severity scores, the physiotherapy exercise programme resulted
      in an improvement in the primary outcome, and modest but consistently better
      secondary outcomes at both time-points compared to the control group. The
      effectiveness in different subgroups requires further direct evaluation.
      CONCLUSIONS: In the treatment of patients with neurogenic claudication symptoms,
      a physiotherapist-prescribed home exercise programme is no more effective than
      advice and education. ETHICAL APPROVAL: The study was approved by Leeds Central
      Ethics Committee and informed consent was given by all participating patients.
      COPYRIGHT: The Corresponding Author has the right to grant on behalf of all
      authors and does grant on behalf of all authors, a worldwide licence to the
      Publishers and its licensees in perpetuity, in all forms, formats and media
      (whether known now or created in the future), to i) publish, reproduce,
      distribute, display and store the Contribution, ii) translate the Contribution
      into other languages, create adaptations, reprints, include within collections
      and create summaries, extracts and/or, abstracts of the Contribution, iii) create
      any other derivative work(s) based on the Contribution, iv) to exploit all
      subsidiary rights in the Contribution, v) the inclusion of electronic links from
      the Contribution to third party material where-ever it may be located; and, vi)
      licence any third party to do any or all of the above. TRIAL REGISTRATION: ISRCTN
      78288224 - doi10.1186/ISRCTN35836727; UKCRN 4814.

PMID- 24098634
TI  - Cardio-metabolic effectsof HIV protease inhibitors (lopinavir/ritonavir).
AB  - Although antiretroviral treatment decreases HIV-AIDS morbidity/mortality, long
      term side effects may include the onset of insulin resistance and cardiovascular
      diseases. However, the underlying molecular mechanisms responsible for highly
      active antiretroviral therapy (HAART)-induced cardio-metabolic effects are poorly
      understood. In light of this, we hypothesized that HIV protease inhibitor (PI)
      treatment (Lopinavir/Ritonavir) elevates myocardial oxidative stress and
      concomitantly inhibits the ubiquitin proteasome system (UPS), thereby attenuating
      cardiac function. Lopinavir/Ritonavir was dissolved in 1% ethanol (vehicle) and
      injected into mini-osmotic pumps that were surgically implanted into Wistar rats
      for 8 weeks vs. vehicle and sham controls. We subsequently evaluated metabolic
      parameters, gene/protein markers and heart function (ex vivo Langendorff
      perfusions). PI-treated rats exhibited increased serum LDL-cholesterol, higher
      tissue triglycerides (heart, liver), but no evidence of insulin resistance. In
      parallel, there was upregulation of hepatic gene expression, i.e. acetyl-CoA
      carboxylase b and 3-hydroxy-3-methylglutaryl-CoA-reductase, key regulators of
      fatty acid oxidation and cholesterol synthesis, respectively. PI-treated hearts
      displayed impaired cardiac contractile function together with attenuated UPS
      activity. However, there was no significant remodeling of hearts exposed to PIs,
      i.e. lack of ultrastructural changes, fibrosis, cardiac hypertrophic response,
      and oxidative stress. Western blot analysis of PI-treated hearts revealed that
      perturbed calcium handling may contribute to the PI-mediated contractile
      dysfunction. Here chronic PI administration led to elevated myocardial
      calcineurin, nuclear factor of activated T-cells 3 (NFAT3), connexin 43, and
      phosphorylated phospholamban, together with decreased calmodulin expression
      levels. This study demonstrates that early changes triggered by PI treatment
      include increased serum LDL-cholesterol levels together with attenuated cardiac
      function. Furthermore, PI exposure inhibits the myocardial UPS and leads to
      elevated calcineurin and connexin 43 expression that may be associated with the
      future onset of cardiac contractile dysfunction.

PMID- 24098635
TI  - Investigating interventions in Alzheimer's disease with computer simulation
      models.
AB  - Progress in the development of therapeutic interventions to treat or slow the
      progression of Alzheimer's disease has been hampered by lack of efficacy and
      unforeseen side effects in human clinical trials. This setback highlights the
      need for new approaches for pre-clinical testing of possible interventions.
      Systems modelling is becoming increasingly recognised as a valuable tool for
      investigating molecular and cellular mechanisms involved in ageing and age
      related diseases. However, there is still a lack of awareness of modelling
      approaches in many areas of biomedical research. We previously developed a
      stochastic computer model to examine some of the key pathways involved in the
      aggregation of amyloid-beta (Abeta) and the micro-tubular binding protein tau.
      Here we show how we extended this model to include the main processes involved in
      passive and active immunisation against Abeta and then demonstrate the effects of
      this intervention on soluble Abeta, plaques, phosphorylated tau and tangles. The
      model predicts that immunisation leads to clearance of plaques but only results
      in small reductions in levels of soluble Abeta, phosphorylated tau and tangles.
      The behaviour of this model is supported by neuropathological observations in
      Alzheimer patients immunised against Abeta. Since, soluble Abeta, phosphorylated
      tau and tangles more closely correlate with cognitive decline than plaques, our
      model suggests that immunotherapy against Abeta may not be effective unless it is
      performed very early in the disease process or combined with other therapies. 

PMID- 24098636
TI  - Temporal feeding pattern may influence reproduction efficiency, the example of
      breeding mares.
AB  - Discomfort in farm animals may be induced by inappropriate types or timing of
      food supplies. Thus, time restriction of meals and lack of roughage have been
      shown to be one source of emergence of oral stereotypies and abnormal behaviour
      in horses which have evolved to eat high-fibre diets in small amounts over long
      periods of time. This feeding pattern is often altered in domestic environment
      where horses are often fed low fibre meals that can be rapidly consumed. This
      study aimed at determining the effect of the temporal pattern of feeding on
      reproductive efficiency of breeding mares, One hundred Arab breeding mares were
      divided into two groups that differed only in the temporal pattern of roughage
      availability: only at night for the standard feeding pattern group (SFP mares),
      night and day for the "continuous feeding" group (CF mares). The total amount of
      roughage provided was the same as the CF mares received half of the hay during
      the day while in paddock (haynets). Mares were tested for oestrus detection by
      teasing with one stallion and were then examined clinically by rectal palpations
      and ultrasound before being mated naturally or inseminated by fresh or frozen
      semen. Multivariate logistic regression was used to analyse data. The treatment
      affected significantly the reproductive efficiency of the mares with fewer
      oestrus abnormalities (p = 0.0002) and more fertility (p = 0.024) in CF mares
      (conception rate = 81% versus 55% in SFP mares). Ensuring semi-continous feeding
      by providing roughage may be a way of fulfilling the basic physiological needs of
      the horses' digestive system, reducing stress and associated inhibitors of
      reproduction. To our knowledge, this study provides the first evidence of an
      impact of temporal feeding patterns on reproductive success in a Mammal. Temporal
      patterns of feeding may be a major and underestimated factor in breeding. 

PMID- 24098637
TI  - Rift valley fever in humans and animals in Mayotte, an endemic situation?
AB  - Retrospective studies and surveillance on humans and animals revealed that Rift
      Valley Fever virus (RVFV) has been circulating on Mayotte for at least several
      years. A study was conducted in 2011 to estimate the seroprevalence of RVF in
      humans and in animals and to identify associated risk factors. Using a multistage
      cluster sampling method, 1420 individuals were enrolled in the human study,
      including 337 children aged 5 to 14 years. For the animal study, 198 seronegative
      ruminants from 33 randomly selected sentinel ruminant herds were followed up for
      more than one year. In both studies, information on environment and risk factors
      was collected through a standardized questionnaire. The overall weighted
      seroprevalence of RVFV antibodies in the general population aged >=5 years was
      3.5% (95% CI 2.6-4.8). The overall seroprevalence of RVFV antibodies in the
      ruminant population was 25.3% (95% CI 19.8-32.2). Age (>=15), gender (men), place
      of birth on the Comoros, living in Mayotte since less than 5 years, low
      educational level, farming and living close to a water source were significantly
      associated with RVFV seropositivity in humans. Major risk factors for RFV
      infection in animals were the proximity of the farm to a water point, previous
      two-month rainfall and absence of abortions disposal. Although resulting in few
      clinical cases in humans and in animals, RVFV has been circulating actively on
      the island of Mayotte, in a context of regular import of the virus from nearby
      countries through illegal animal movements, the presence of susceptible animals
      and a favorable environment for mosquito vectors to maintain virus transmission
      locally. Humans and animals share the same ways of RVFV transmission, with
      mosquitoes playing an important role. The studies emphasize the need for a one
      health approach in which humans and animals within their ecosystems are included.

PMID- 24098638
TI  - Telomere reprogramming and maintenance in porcine iPS cells.
AB  - Telomere reprogramming and silencing of exogenous genes have been demonstrated in
      mouse and human induced pluripotent stem cells (iPS cells). Pigs have the
      potential to provide xenotransplant for humans, and to model and test human
      diseases. We investigated the telomere length and maintenance in porcine iPS
      cells generated and cultured under various conditions. Telomere lengths vary
      among different porcine iPS cell lines, some with telomere elongation and
      maintenance, and others telomere shortening. Porcine iPS cells with sufficient
      telomere length maintenance show the ability to differentiate in vivo by teratoma
      formation test. IPS cells with short or dysfunctional telomeres exhibit reduced
      ability to form teratomas. Moreover, insufficient telomerase and incomplete
      telomere reprogramming and/or maintenance link to sustained activation of
      exogenous genes in porcine iPS cells. In contrast, porcine iPS cells with reduced
      expression of exogenous genes or partial exogene silencing exhibit insufficient
      activation of endogenous pluripotent genes and telomerase genes, accompanied by
      telomere shortening with increasing passages. Moreover, telomere doublets,
      telomere sister chromatid exchanges and t-circles that presumably are involved in
      telomere lengthening by recombination also are found in porcine iPS cells. These
      data suggest that both telomerase-dependent and telomerase-independent mechanisms
      are involved in telomere reprogramming during induction and passages of porcine
      iPS cells, but these are insufficient, resulting in increased telomere damage and
      shortening, and chromosomal instability. Active exogenes might compensate for
      insufficient activation of endogenous genes and incomplete telomere reprogramming
      and maintenance of porcine iPS cells. Further understanding of telomere
      reprogramming and maintenance may help improve the quality of porcine iPS cells. 

PMID- 24098639
TI  - New potential therapeutic approach for the treatment of B-Cell malignancies using
      chlorambucil/hydroxychloroquine-loaded anti-CD20 nanoparticles.
AB  - Current B-cell disorder treatments take advantage of dose-intensive chemotherapy
      regimens and immunotherapy via use of monoclonal antibodies. Unfortunately, they
      may lead to insufficient tumor distribution of therapeutic agents, and often
      cause adverse effects on patients. In this contribution, we propose a novel
      therapeutic approach in which relatively high doses of Hydroxychloroquine and
      Chlorambucil were loaded into biodegradable nanoparticles coated with an anti
      CD20 antibody. We demonstrate their ability to effectively target and internalize
      in tumor B-cells. Moreover, these nanoparticles were able to kill not only p53
      mutated/deleted lymphoma cell lines expressing a low amount of CD20, but also
      circulating primary cells purified from chronic lymphocitic leukemia patients.
      Their safety was demonstrated in healthy mice, and their therapeutic effects in a
      new model of Burkitt's lymphoma. The latter serves as a prototype of an
      aggressive lympho-proliferative disease. In vitro and in vivo data showed the
      ability of anti-CD20 nanoparticles loaded with Hydroxychloroquine and
      Chlorambucil to increase tumor cell killing in comparison to free cytotoxic
      agents or Rituximab. These results shed light on the potential of anti-CD20
      nanoparticles carrying Hydroxychloroquine and Chlorambucil for controlling a
      disseminated model of aggressive lymphoma, and lend credence to the idea of
      adopting this therapeutic approach for the treatment of B-cell disorders. 

PMID- 24098640
TI  - Trajectory adjustments underlying task-specific intermittent force behaviors and
      muscular rhythms.
AB  - Force intermittency is one of the major causes of motor variability. Focusing on
      the dynamics of force intermittency, this study was undertaken to investigate how
      force trajectory is fine-tuned for static and dynamic force-tracking of a
      comparable physical load. Twenty-two healthy adults performed two unilateral
      resistance protocols (static force-tracking at 75% maximal effort and dynamic
      force-tracking in the range of 50%-100% maximal effort) using the left hand. The
      electromyographic activity and force profile of the designated hand were
      monitored. Gripping force was off-line decomposed into a primary movement
      spectrally identical to the target motion and a force intermittency profile
      containing numerous force pulses. The results showed that dynamic force-tracking
      exhibited greater intermittency amplitude and force pulse but a smaller amplitude
      ratio of primary movement to force intermittency than static force-tracking.
      Multi-scale entropy analysis revealed that force intermittency during dynamic
      force-tracking was more complex on a low time scale but more regular on a high
      time scale than that of static force-tracking. Together with task-dependent force
      intermittency properties, dynamic force-tracking exhibited a smaller 8-12 Hz
      muscular oscillation but a more potentiated muscular oscillation at 35-50 Hz than
      static force-tracking. In conclusion, force intermittency reflects differing
      trajectory controls for static and dynamic force-tracking. The target goal of
      dynamic tracking is achieved through trajectory adjustments that are more
      intricate and more frequent than those of static tracking, pertaining to
      differing organizations and functioning of muscular oscillations in the alpha and
      gamma bands. 

PMID- 24098641
TI  - Prediction of rat behavior outcomes in memory tasks using functional connections
      among neurons.
AB  - BACKGROUND: Analyzing the neuronal organizational structures and studying the
      changes in the behavior of the organism is key to understanding cognitive
      functions of the brain. Although some studies have indicated that spatiotemporal
      firing patterns of neuronal populations have a certain relationship with the
      behavioral responses, the issues of whether there are any relationships between
      the functional networks comprised of these cortical neurons and behavioral tasks
      and whether it is possible to take advantage of these networks to predict correct
      and incorrect outcomes of single trials of animals are still unresolved.
      METHODOLOGY/PRINCIPAL FINDINGS: This paper presents a new method of analyzing the
      structures of whole-recorded neuronal functional networks (WNFNs) and local
      neuronal circuit groups (LNCGs). The activity of these neurons was recorded in
      several rats. The rats performed two different behavioral tasks, the Y-maze task
      and the U-maze task. Using the results of the assessment of the WNFNs and LNCGs,
      this paper describes a realization procedure for predicting the behavioral
      outcomes of single trials. The methodology consists of four main parts:
      construction of WNFNs from recorded neuronal spike trains, partitioning the WNFNs
      into the optimal LNCGs using social community analysis, unsupervised clustering
      of all trials from each dataset into two different clusters, and predicting the
      behavioral outcomes of single trials. The results show that WNFNs and LNCGs
      correlate with the behavior of the animal. The U-maze datasets show higher
      accuracy for unsupervised clustering results than those from the Y-maze task, and
      these datasets can be used to predict behavioral responses effectively.
      CONCLUSIONS/SIGNIFICANCE: The results of the present study suggest that a
      methodology proposed in this paper is suitable for analysis of the
      characteristics of neuronal functional networks and the prediction of rat
      behavior. These types of structures in cortical ensemble activity may be critical
      to information representation during the execution of behavior.

PMID- 24098642
TI  - Lessons learned from quantitative dynamical modeling in systems biology.
AB  - Due to the high complexity of biological data it is difficult to disentangle
      cellular processes relying only on intuitive interpretation of measurements. A
      Systems Biology approach that combines quantitative experimental data with
      dynamic mathematical modeling promises to yield deeper insights into these
      processes. Nevertheless, with growing complexity and increasing amount of
      quantitative experimental data, building realistic and reliable mathematical
      models can become a challenging task: the quality of experimental data has to be
      assessed objectively, unknown model parameters need to be estimated from the
      experimental data, and numerical calculations need to be precise and efficient.
      Here, we discuss, compare and characterize the performance of computational
      methods throughout the process of quantitative dynamic modeling using two
      previously established examples, for which quantitative, dose- and time-resolved
      experimental data are available. In particular, we present an approach that
      allows to determine the quality of experimental data in an efficient, objective
      and automated manner. Using this approach data generated by different measurement
      techniques and even in single replicates can be reliably used for mathematical
      modeling. For the estimation of unknown model parameters, the performance of
      different optimization algorithms was compared systematically. Our results show
      that deterministic derivative-based optimization employing the sensitivity
      equations in combination with a multi-start strategy based on latin hypercube
      sampling outperforms the other methods by orders of magnitude in accuracy and
      speed. Finally, we investigated transformations that yield a more efficient
      parameterization of the model and therefore lead to a further enhancement in
      optimization performance. We provide a freely available open source software
      package that implements the algorithms and examples compared here. 

PMID- 24098643
TI  - The structure of neuronal calcium sensor-1 in solution revealed by molecular
      dynamics simulations.
AB  - Neuronal calcium sensor-1 (NCS-1) is a protein able to trigger signal
      transduction processes by binding a large number of substrates and re-shaping its
      structure depending on the environmental conditions. The X-ray crystal structure
      of the unmyristoilated NCS-1 shows a large solvent-exposed hydrophobic crevice
      (HC); this HC is partially occupied by the C-terminal tail and thus elusive to
      the surrounding solvent. We studied the native state of NCS-1 by performing room
      temperature molecular dynamics (MD) simulations starting from the crystal and the
      solution structures. We observe relaxation to a state independent of the initial
      structure, in which the C-terminal tail occupies the HC. We suggest that the C
      terminal tail shields the HC binding pocket and modulates the affinity of NCS-1
      for its natural targets. By analyzing the topology and nature of the inter
      residue potential energy, we provide a compelling description of the interaction
      network that determines the three-dimensional organization of NCS-1. 

PMID- 24098644
TI  - The market dynamics of generic medicines in the private sector of 19 low and
      middle income countries between 2001 and 2011: a descriptive time series
      analysis.
AB  - This observational study investigates the private sector, retail pharmaceutical
      market of 19 low and middle income countries (LMICs) in Latin America, Asia and
      the Middle East/South Africa analyzing the relationships between volume market
      share of generic and originator medicines over a time series from 2001 to 2011.
      Over 5000 individual pharmaceutical substances were divided into generic
      (unbranded generic, branded generic medicines) and originator categories for each
      country, including the United States as a comparator. In 9 selected LMICs, the
      market share of those originator substances with the largest decrease over time
      was compared to the market share of their counterpart generic versions. Generic
      medicines (branded generic plus unbranded generic) represent between 70 and 80%
      of market share in the private sector of these LMICs which exceeds that of most
      European countries. Branded generic medicine market share is higher than that of
      unbranded generics in all three regions and this is in contrast to the U.S.
      Although switching from an originator to its generic counterpart can save money,
      this narrative in reality is complex at the level of individual medicines. In
      some countries, the market behavior of some originator medicines that showed the
      most temporal decrease, showed switching to their generic counterpart. In other
      countries such as in the Middle East/South Africa and Asia, the loss of these
      originators was not accompanied by any change at all in market share of the
      equivalent generic version. For those countries with a significant increase in
      generic medicines market share and/or with evidence of comprehensive "switching"
      to generic versions, notably in Latin America, it would be worthwhile to
      establish cause-effect relationships between pharmaceutical policies and uptake
      of generic medicines. The absence of change in the generic medicines market share
      in other countries suggests that, at a minimum, generic medicines have not been
      strongly promoted. 

PMID- 24098645
TI  - Fibroblast growth factor-2 induced by enriched environment enhances angiogenesis
      and motor function in chronic hypoxic-ischemic brain injury.
AB  - This study aimed to investigate the effects of enriched environment (EE) on
      promoting angiogenesis and neurobehavioral function in an animal model of chronic
      hypoxic-ischemic (HI) brain injury. HI brain damage was induced in seven day-old
      CD-1(r) mice by unilateral carotid artery ligation and exposure to hypoxia (8% O2
      for 90 min). At six weeks of age, the mice were randomly assigned to either EE or
      standard cages (SC) for two months. Rotarod, forelimb-use asymmetry, and grip
      strength tests were performed to evaluate neurobehavioral function. In order to
      identify angiogenic growth factors regulated by EE, an array-based multiplex
      ELISA assay was used to measure the expression in frontal cortex, striatum, and
      cerebellum. Among the growth factors, the expression of fibroblast growth factor
      2 (FGF-2) was confirmed using western blotting. Platelet endothelial cell
      adhesion molecule-1 (PECAM-1) and alpha-smooth muscle actin (alpha-SMA) were also
      evaluated using immunohistochemistry. As a result, mice exposed to EE showed
      significant improvements in rotarod and ladder walking performances compared to
      SC controls. The level of FGF-2 was significantly higher in the frontal cortex of
      EE mice at 8 weeks after treatment in multiplex ELISA and western blot. On the
      other hand, FGF-2 in the striatum significantly increased at 2 weeks after
      exposure to EE earlier than in the frontal cortex. Expression of activin A was
      similarly upregulated as FGF-2 expression pattern. Particularly, all animals
      treated with FGF-2 neutralizing antibody abolished the beneficial effect of EE on
      motor performance relative to mice not given anti-FGF-2. Immunohistochemistry
      showed that densities of alpha-SMA(+) and PECAM-1(+) cells in frontal cortex,
      striatum, and hippocampus were significantly increased following EE, suggesting
      the histological findings exhibit a similar pattern to the upregulation of FGF-2
      in the brain. In conclusion, EE enhances endogenous angiogenesis and
      neurobehavioral functions mediated by upregulation of FGF-2 in chronic hypoxic
      ischemic brain injury. 

PMID- 24098646
TI  - New measure of insulin sensitivity predicts cardiovascular disease better than
      HOMA estimated insulin resistance.
AB  - CONTEXT: Accurate assessment of insulin sensitivity may better identify
      individuals at increased risk of cardio-metabolic diseases. OBJECTIVES: To
      examine whether a combination of anthropometric, biochemical and imaging measures
      can better estimate insulin sensitivity index (ISI) and provide improved
      prediction of cardio-metabolic risk, in comparison to HOMA-IR. DESIGN AND
      PARTICIPANTS: Healthy male volunteers (96 Chinese, 80 Malay, 77 Indian), 21 to 40
      years, body mass index 18-30 kg/m(2). Predicted ISI (ISI-cal) was generated using
      45 randomly selected Chinese through stepwise multiple linear regression, and
      validated in the rest using non-parametric correlation (Kendall's tau tau). In an
      independent longitudinal cohort, ISI-cal and HOMA-IR were compared for prediction
      of diabetes and cardiovascular disease (CVD), using ROC curves. SETTING: The
      study was conducted in a university academic medical centre. OUTCOME MEASURES:
      ISI measured by hyperinsulinemic euglycemic glucose clamp, along with
      anthropometric measurements, biochemical assessment and imaging; incident
      diabetes and CVD. RESULTS: A combination of fasting insulin, serum triglycerides
      and waist-to-hip ratio (WHR) provided the best estimate of clamp-derived ISI
      (adjusted R(2) 0.58 versus 0.32 HOMA-IR). In an independent cohort, ROC areas
      under the curve were 0.77+/-0.02 ISI-cal versus 0.76+/-0.02 HOMA-IR (p>0.05) for
      incident diabetes, and 0.74+/-0.03 ISI-cal versus 0.61+/-0.03 HOMA-IR (p<0.001)
      for incident CVD. ISI-cal also had greater sensitivity than defined metabolic
      syndrome in predicting CVD, with a four-fold increase in the risk of CVD
      independent of metabolic syndrome. CONCLUSIONS: Triglycerides and WHR, combined
      with fasting insulin levels, provide a better estimate of current insulin
      resistance state and improved identification of individuals with future risk of
      CVD, compared to HOMA-IR. This may be useful for estimating insulin sensitivity
      and cardio-metabolic risk in clinical and epidemiological settings.

PMID- 24098647
TI  - Preparation and characterization of selenium incorporated guar gum nanoparticle
      and its interaction with H9c2 cells.
AB  - This study deals with the preparation and characterization of selenium
      incorporated guar gum nanoparticle (SGG), and its effect on H9c2 cardiomyoblast.
      Herein, nanoprecipitation techniques had been employed for the preparation of SGG
      nanoparticle. The prepared nanoparticle had been subjected to various types of
      analytical techniques like transmission electron microscopy (TEM), X-ray
      diffraction (XRD) and particle size analysis to confirm the characteristics of
      nanoparticle as well as for selenium incorporation. Physical characterization of
      nanoparticle showed that the size of nanoparticles increase upto ~69-173 nm upon
      selenium incorporation from ~41-132 nm. Then the prepared nanoparticles were
      evaluated for its effect on H9c2 cells. In this regard, the effect of
      nanoparticle on various vital parameters of H9c2 cells was studied. Parameters
      like cell viability, uptake of selenium incorporated guar gum nanoparticle by the
      cells, effect of SGG on DNA integrity, apoptosis, reactive oxygen species
      generation, alteration in transmembrane potential of mitochondria and
      cytoskeletal integrity had been investigated. Viability results showed that up to
      25 nM of SGG was safe (10.31%) but beyond that it induces cytotoxicity. Cellular
      uptake of selenium showed that cell permeability for SGG is significantly high
      compared to normal selenium (7.2 nM of selenium for 25 nM SGG compared with 5.2
      nM selenium for 25 nM sodium selenite). There was no apoptosis with SGG and also
      it protects DNA from hydroxyl radical induced breakage. Likewise no adverse
      effect on mitochondria and cytoskeleton was observed for 25 nM of SGG. Overall
      results reveal that SGG is highly suitable for biomedical research application. 

PMID- 24098648
TI  - The detection of surfactant proteins A, B, C and D in the human brain and their
      regulation in cerebral infarction, autoimmune conditions and infections of the
      CNS.
AB  - Surfactant proteins (SP) have been studied intensively in the respiratory system.
      Surfactant protein A and surfactant protein D are proteins belonging to the
      family of collectins each playing a major role in the innate immune system. The
      ability of surfactant protein A and surfactant protein D to bind various
      pathogens and facilitate their elimination has been described in a vast number of
      studies. Surfactant proteins are very important in modulating the host's
      inflammatory response and participate in the clearance of apoptotic cells.
      Surfactant protein B and surfactant protein C are proteins responsible for
      lowering the surface tension in the lungs. The aim of this study was an
      investigation of expression of surfactant proteins in the central nervous system
      to assess their specific distribution patterns. The second aim was to quantify
      surfactant proteins in cerebrospinal fluid of healthy subjects compared to
      patients suffering from different neuropathologies. The expression of mRNA for
      the surfactant proteins was analyzed with RT-PCR done with samples from different
      parts of the human brain. The production of the surfactant proteins in the brain
      was verified using immunohistochemistry and Western blot. The concentrations of
      the surfactant proteins in cerebrospinal fluid from healthy subjects and patients
      suffering from neuropathologic conditions were quantified using ELISA. Our
      results revealed that surfactant proteins are present in the central nervous
      system and that the concentrations of one or more surfactant proteins in healthy
      subjects differed significantly from those of patients affected by central
      autoimmune processes, CNS infections or cerebral infarction. Based on the
      localization of the surfactant proteins in the brain, their different levels in
      normal versus pathologic samples of cerebrospinal fluid and their well-known
      functions in the lungs, it appears that the surfactant proteins may play roles in
      host defense of the brain, facilitation of cerebrospinal fluid secretion and
      maintenance of the latter's rheological properties. 

PMID- 24098649
TI  - A biosynthetic nerve guide conduit based on silk/SWNT/fibronectin nanocomposite
      for peripheral nerve regeneration.
AB  - As a contribution to the functionality of nerve guide conduits (NGCs) in nerve
      tissue engineering, here we report a conduit processing technique through
      introduction and evaluation of topographical, physical and chemical cues. Porous
      structure of NGCs based on freeze-dried silk/single walled carbon nanotubes
      (SF/SWNTs) has shown a uniform chemical and physical structure with suitable
      electrical conductivity. Moreover, fibronectin (FN) containing nanofibers within
      the structure of SF/SWNT conduits produced through electrospinning process have
      shown aligned fashion with appropriate porosity and diameter. Moreover,
      fibronectin remained its bioactivity and influenced the adhesion and growth of
      U373 cell lines. The conduits were then implanted to 10 mm left sciatic nerve
      defects in rats. The histological assessment has shown that nerve regeneration
      has taken places in proximal region of implanted nerve after 5 weeks following
      surgery. Furthermore, nerve conduction velocities (NCV) and more myelinated axons
      were observed in SF/SWNT and SF/SWNT/FN groups after 5 weeks post implantation,
      indicating a functional recovery for the injured nerves. With
      immunohistochemistry, the higher S-100 expression of Schwann cells in SF/SWNT/FN
      conduits in comparison to other groups was confirmed. In conclusion, an oriented
      conduit of biocompatible SF/SWNT/FN has been fabricated with acceptable structure
      that is particularly applicable in nerve grafts. 

PMID- 24098650
TI  - Serum ghrelin; a new surrogate marker of gastric mucosal alterations in upper
      gastrointestinal carcinogenesis.
AB  - BACKGROUND: A few studies have indicated inverse relationships between serum
      ghrelin and gastric and esophageal cancers but those associations have been
      restricted to specific populations, including smokers and overweight individuals.
      We examined the association between ghrelin and gastroesophageal cancers and
      atrophic gastritis in a population-based setting. METHODS: In total 220
      gastroesophageal cancers, comprising non-cardia and cardia gastric cancer,
      esophageal adenocarcinoma, esophageal squamous cell carcinoma (SCC) and age and
      gender-matched controls were recruited. Serum ghrelin, pepsinogen I/II ratio
      (PGI/II) and anti-H.pylori IgG antibodies were measured. Relationships between
      ghrelin and gastroesophageal cancers, after adjustment for PGI/II ratio, H.pylori
      status and smoking, were tested using logistic regression. Furthermore, in 125
      endoscopically normal volunteers, with and without histological atrophic
      gastritis, the relationship with ghrelin was compared. RESULTS: Serum ghrelin
      (lowest vs. highest quintile) was inversely associated with gastric cancer: OR
      (95% CI) 8.71 (1.70-44.59) for cardia and 6.58 (1.26-34.46) for non-cardia
      cancer. Lower serum ghrelin was also associated with esophageal SCC: OR (95% CI)
      5.69 (1.36-23.78), but not with esophageal adenocarcinoma. A similar association
      was observed between gastric cancer (cardia and non-cardia) and esophageal SCC
      when serum ghrelin was analysed as a continuous scaled variable. In
      endoscopically-normal volunteers, extensive atrophic gastritis was associated
      with low serum ghrelin [OR (95% CI) 0.25 (0.10-0.64)]. CONCLUSION: Inverse
      associations between ghrelin and some gastroesophageal cancers suggest a
      potential role for serum ghrelin as a biomarker of upper gastrointestinal cancers
      and atrophic gastritis. In areas with a high incidence of gastric and/or
      esophageal cancer, screening might be more effectively targeted to individuals
      with low serum ghrelin in addition to the PGI/II ratio.

PMID- 24098651
TI  - Optimizing scoring function of protein-nucleic acid interactions with both
      affinity and specificity.
AB  - Protein-nucleic acid (protein-DNA and protein-RNA) recognition is fundamental to
      the regulation of gene expression. Determination of the structures of the protein
      nucleic acid recognition and insight into their interactions at molecular level
      are vital to understanding the regulation function. Recently, quantitative
      computational approach has been becoming an alternative of experimental technique
      for predicting the structures and interactions of biomolecular recognition.
      However, the progress of protein-nucleic acid structure prediction, especially
      protein-RNA, is far behind that of the protein-ligand and protein-protein
      structure predictions due to the lack of reliable and accurate scoring function
      for quantifying the protein-nucleic acid interactions. In this work, we developed
      an accurate scoring function (named as SPA-PN, SPecificity and Affinity of the
      Protein-Nucleic acid interactions) for protein-nucleic acid interactions by
      incorporating both the specificity and affinity into the optimization strategy.
      Specificity and affinity are two requirements of highly efficient and specific
      biomolecular recognition. Previous quantitative descriptions of the biomolecular
      interactions considered the affinity, but often ignored the specificity owing to
      the challenge of specificity quantification. We applied our concept of intrinsic
      specificity to connect the conventional specificity, which circumvents the
      challenge of specificity quantification. In addition to the affinity
      optimization, we incorporated the quantified intrinsic specificity into the
      optimization strategy of SPA-PN. The testing results and comparisons with other
      scoring functions validated that SPA-PN performs well on both the prediction of
      binding affinity and identification of native conformation. In terms of its
      performance, SPA-PN can be widely used to predict the protein-nucleic acid
      structures and quantify their interactions. 

PMID- 24098652
TI  - Homologous recombination occurs in Entamoeba and is enhanced during growth stress
      and stage conversion.
AB  - Homologous recombination (HR) has not been demonstrated in the parasitic protists
      Entamoeba histolytica or Entamoeba invadens, as no convenient method is available
      to measure it. However, HR must exist to ensure genome integrity, and possible
      genetic exchange, especially during stage conversion from trophozoite to cyst.
      Here we show the up regulation of mitotic and meiotic HR genes in Entamoeba
      during serum starvation, and encystation. To directly demonstrate HR we use a
      simple PCR-based method involving inverted repeats, which gives a reliable read
      out, as the recombination junctions can be determined by sequencing the
      amplicons. Using this read out, we demonstrate enhanced HR under growth stress in
      E. histolytica, and during encystation in E. invadens. We also demonstrate
      recombination between chromosomal inverted repeats. This is the first
      experimental demonstration of HR in Entamoeba and will help future investigations
      into this process, and to explore the possibility of meiosis in Entamoeba. 

PMID- 24098653
TI  - High resolution crystal structure of the Grb2 SH2 domain with a phosphopeptide
      derived from CD28.
AB  - Src homology 2 (SH2) domains play a critical role in cellular signal
      transduction. They bind to peptides containing phosphotyrosine (pY) with various
      specificities that depend on the flanking amino-acid residues. The SH2 domain of
      growth-factor receptor-bound protein 2 (Grb2) specifically recognizes pY-X-N-X,
      whereas the SH2 domains in phosphatidylinositol 3-kinase (PI3K) recognize pY-X-X
      M. Binding of the pY site in CD28 (pY-M-N-M) by PI3K and Grb2 through their SH2
      domains is a key step that triggers the CD28 signal transduction for T cell
      activation and differentiation. In this study, we determined the crystal
      structure of the Grb2 SH2 domain in complex with a pY-containing peptide derived
      from CD28 at 1.35 A resolution. The peptide was found to adopt a twisted U-type
      conformation, similar to, but distinct from type-I beta-turn. In all previously
      reported crystal structures, the peptide bound to the Grb2 SH2 domains adopts a
      type-I beta-turn conformation, except those with a proline residue at the pY+3
      position. Molecular modeling also suggests that the same peptide bound to PI3K
      might adopt a very different conformation. 

PMID- 24098654
TI  - (1)H-NMR spectroscopy revealed Mycobacterium tuberculosis caused abnormal serum
      metabolic profile of cattle.
AB  - To re-evaluate virulence of Mycobacterium tuberculosis (M. tb) in cattle, we
      experimentally infected calves with M. tb andMycobacterium bovisvia intratracheal
      injection at a dose of 2.0*10(7) CFU and observed the animals for 33 weeks. The
      intradermal tuberculin test and IFN-gammain vitro release assay showed that both
      M. tb and M. bovis induced similar responses. Immunohistochemical staining of
      pulmonary lymph nodes indicated that the antigen MPB83 of both M. tb and M. bovis
      were similarly distributed in the tissue samples. Histological examinations
      showed all of the infected groups exhibited neutrophil infiltration to similar
      extents. Although the infected cattle did not develop granulomatous inflammation,
      the metabolic profiles changed significantly, which were characterized by a
      change in energy production pathways and increased concentrations of N-acetyl
      glycoproteins. Glycolysis was induced in the infected cattle by decreased glucose
      and increased lactate content, and enhanced fatty acid beta-oxidation was induced
      by decreased TG content, and decreased gluconeogenesis indicated by the decreased
      concentration of glucogenic and ketogenic amino acids promoted utilization of
      substances other than glucose as energy sources. In addition, an increase in
      acute phase reactive serum glycoproteins, together with neutrophil infiltration
      and increased of IL-1beta production indicated an early inflammatory response
      before granuloma formation. In conclusion, this study indicated that both M. tb
      and M.bovis were virulent to cattle. Therefore, it is likely that cattle with M.
      tb infections would be critical to tuberculosis transmission from cattle to
      humans. Nuclear magnetic resonance was demonstrated to be an efficient method to
      systematically evaluate M. tb and M. bovi sinfection in cattle. 

PMID- 24098656
TI  - Climatic facilitation of the colonization of an estuary by Acartia tonsa.
AB  - Global change has become a major driving force of both terrestrial and marine
      systems. Located at the interface between these two realms, estuarine ecosystems
      are probably the place where both direct and indirect effects of human activities
      conspire together to affect biodiversity from phytoplankton to top predators.
      Among European estuarine systems, the Gironde is the largest estuary of Western
      Europe and many studies have provided evidence that it has been affected by a
      variety of anthropogenic stressors such as thermal and chemical pollution,
      physical alterations and exploitation, especially for maritime traffic. In such a
      context, species introduction is also a current major issue with the
      establishment of strong competitive species that could lead to ecosystem
      reorganization with potential decrease or even disappearance of native species.
      In the Gironde estuary, this hypothesis was proposed for the invasive shrimp
      species Palaemon macrodactylus as a decrease in the native species abundance was
      observed at the same time. Although species introduction often takes place via
      ballast water, the influence of climate-driven changes on the establishment of
      new species remains a key issue. The calanoid copepod Acartia tonsa, observed in
      the Gironde estuary for the first time in 1983, have since colonized most part of
      the estuary, reaching a level of abundance comparable to the dominant native
      species Eurytemora affinis. In this study, using both the concept of the
      ecological niche sensu Hutchinson (fundamental and realized niches) and
      statistical models, we reveal that the dynamics of the colonization of A. tonsa
      was facilitated by environmental conditions that have become closer to its
      environmental optimum with respect to temperature and salinity. 

PMID- 24098655
TI  - A small volatile bacterial molecule triggers mitochondrial dysfunction in murine
      skeletal muscle.
AB  - Mitochondria integrate distinct signals that reflect specific threats to the
      host, including infection, tissue damage, and metabolic dysfunction; and play a
      key role in insulin resistance. We have found that the Pseudomonas aeruginosa
      quorum sensing infochemical, 2-amino acetophenone (2-AA), produced during acute
      and chronic infection in human tissues, including in the lungs of cystic fibrosis
      (CF) patients, acts as an interkingdom immunomodulatory signal that facilitates
      pathogen persistence, and host tolerance to infection. Transcriptome results have
      led to the hypothesis that 2-AA causes further harm to the host by triggering
      mitochondrial dysfunction in skeletal muscle. As normal skeletal muscle function
      is essential to survival, and is compromised in many chronic illnesses, including
      infections and CF-associated muscle wasting, we here determine the global effects
      of 2-AA on skeletal muscle using high-resolution magic-angle-spinning (HRMAS),
      proton ((1)H) nuclear magnetic resonance (NMR) metabolomics, in vivo (31)P NMR,
      whole-genome expression analysis and functional studies. Our results show that 2
      AA when injected into mice, induced a biological signature of insulin resistance
      as determined by (1)H NMR analysis-, and dramatically altered insulin signaling,
      glucose transport, and mitochondrial function. Genes including Glut4, IRS1, PPAR
      gamma, PGC1 and Sirt1 were downregulated, whereas uncoupling protein UCP3 was up
      regulated, in accordance with mitochondrial dysfunction. Although 2-AA did not
      alter high-energy phosphates or pH by in vivo (31)P NMR analysis, it
      significantly reduced the rate of ATP synthesis. This affect was corroborated by
      results demonstrating down-regulation of the expression of genes involved in
      energy production and muscle function, and was further validated by muscle
      function studies. Together, these results further demonstrate that 2-AA, acts as
      a mediator of interkingdom modulation, and likely effects insulin resistance
      associated with a molecular signature of mitochondrial dysfunction in skeletal
      muscle. Reduced energy production and mitochondrial dysfunctional may further
      favor infection, and be an important step in the establishment of chronic and
      persistent infections. 

PMID- 24098657
TI  - A descriptive analysis of oral health systematic reviews published 1991-2012:
      cross sectional study.
AB  - OBJECTIVES: To identify all systematic reviews (SRs) published in the domain of
      oral health research and describe them in terms of their epidemiological and
      descriptive characteristics. DESIGN: Cross sectional, descriptive study. METHODS:
      An electronic search of seven databases was performed from inception through May
      2012; bibliographies of relevant publications were also reviewed. Studies were
      considered for inclusion if they were oral health SRs defined as therapeutic or
      non-therapeutic investigations that studied a topic or an intervention related to
      dental, oral or craniofacial diseases/disorders. Data were extracted from all the
      SRs based on a number of epidemiological and descriptive characteristics. Data
      were analysed descriptively for all the SRs, within each of the nine dental
      specialities, and for Cochrane and non-Cochrane SRs separately. RESULTS: 1,188
      oral health (126 Cochrane and 1062 non-Cochrane) SRs published from 1991 through
      May 2012 were identified, encompassing the nine dental specialties. Over half (n
      = 676; 56.9%) of the SRs were published in specialty oral health journals, with
      almost all (n = 1,178; 99.2%) of the SRs published in English and almost none of
      the non-Cochrane SRs (n = 11; 0.9%) consisting of updates of previously published
      SRs. 75.3% of the SRs were categorized as therapeutic, with 64.5% examining non
      drug interventions, while approximately half (n = 150/294; 51%) of the non
      therapeutic SRs were classified as epidemiological SRs. The SRs included a median
      of 15 studies, with a meta-analysis conducted in 43.6%, in which a median of 9
      studies/1 randomized trial were included in the largest meta-analysis conducted.
      Funding was received for 25.1% of the SRs, including nearly three-quarters (n =
      96; 76.2%) of the Cochrane SRs. CONCLUSION: Epidemiological and descriptive
      characteristics of the 1,188 oral health SRs varied across the nine dental
      specialties and by SR category (Cochrane vs. non-Cochrane). There is a clear need
      for more updates of SRs in all the dental specialties.

PMID- 24098658
TI  - Genome sequence analysis of dengue virus 1 isolated in Key West, Florida.
AB  - Dengue virus (DENV) is transmitted to humans through the bite of mosquitoes. In
      November 2010, a dengue outbreak was reported in Monroe County in southern
      Florida (FL), including greater than 20 confirmed human cases. The virus
      collected from the human cases was verified as DENV serotype 1 (DENV-1) and one
      isolate was provided for sequence analysis. RNA was extracted from the DENV-1
      isolate and was used in reverse transcription polymerase chain reaction (RT-PCR)
      to amplify PCR fragments to sequence. Nucleic acid primers were designed to
      generate overlapping PCR fragments that covered the entire genome. The DENV-1
      isolate found in Key West (KW), FL was sequenced for whole genome
      characterization. Sequence assembly, Genbank searches, and recombination analyses
      were performed to verify the identity of the genome sequences and to determine
      percent similarity to known DENV-1 sequences. We show that the KW DENV-1 strain
      is 99% identical to Nicaraguan and Mexican DENV-1 strains. Phylogenetic and
      recombination analyses suggest that the DENV-1 isolated in KW originated from
      Nicaragua (NI) and the KW strain may circulate in KW. Also, recombination
      analysis results detected recombination events in the KW strain compared to DENV
      1 strains from Puerto Rico. We evaluate the relative growth of KW strain of DENV
      1 compared to other dengue viruses to determine whether the underlying genetics
      of the strain is associated with a replicative advantage, an important
      consideration since local transmission of DENV may result because domestic
      tourism can spread DENVs. 

PMID- 24098659
TI  - Structural characterization of the binding interactions of various endogenous
      estrogen metabolites with human estrogen receptor alpha and beta subtypes: a
      molecular modeling study.
AB  - In the present study, we used the molecular docking approach to study the binding
      interactions of various derivatives of 17beta-estradiol (E2) with human estrogen
      receptor (ER) alpha and beta. First, we determined the suitability of the
      molecular docking method to correctly predict the binding modes and interactions
      of two representative agonists (E2 and diethylstilbesterol) in the ligand binding
      domain (LBD) of human ERalpha. We showed that the docked structures of E2 and
      diethylstilbesterol in the ERalpha LBD were almost exactly the same as the known
      crystal structures of ERalpha in complex with these two estrogens. Using the same
      docking approach, we then characterized the binding interactions of 27
      structurally similar E2 derivatives with the LBDs of human ERalpha and ERbeta.
      While the binding modes of these E2 derivatives are very similar to that of E2,
      there are distinct subtle differences, and these small differences contribute
      importantly to their differential binding affinities for ERs. In the case of A
      ring estrogen derivatives, there is a strong inverse relationship between the
      length of the hydrogen bonds formed with ERs and their binding affinity. We found
      that a better correlation between the computed binding energy values and the
      experimentally determined logRBA values could be achieved for various A-ring
      derivatives by re-adjusting the relative weights of the van der Waals interaction
      energy and the Coulomb interaction energy in computing the overall binding energy
      values. 

PMID- 24098660
TI  - Targeted social mobilization in a global manhunt.
AB  - Social mobilization, the ability to mobilize large numbers of people via social
      networks to achieve highly distributed tasks, has received significant attention
      in recent times. This growing capability, facilitated by modern communication
      technology, is highly relevant to endeavors which require the search for
      individuals that possess rare information or skills, such as finding medical
      doctors during disasters, or searching for missing people. An open question
      remains, as to whether in time-critical situations, people are able to recruit in
      a targeted manner, or whether they resort to so-called blind search, recruiting
      as many acquaintances as possible via broadcast communication. To explore this
      question, we examine data from our recent success in the U.S. State Department's
      Tag Challenge, which required locating and photographing 5 target persons in 5
      different cities in the United States and Europe - in under 12 hours - based only
      on a single mug-shot. We find that people are able to consistently route
      information in a targeted fashion even under increasing time pressure. We derive
      an analytical model for social-media fueled global mobilization and use it to
      quantify the extent to which people were targeting their peers during
      recruitment. Our model estimates that approximately 1 in 3 messages were of
      targeted fashion during the most time-sensitive period of the challenge. This is
      a novel observation at such short temporal scales, and calls for opportunities
      for devising viral incentive schemes that provide distance or time-sensitive
      rewards to approach the target geography more rapidly. This observation of '12
      hours of separation' between individuals has applications in multiple areas from
      emergency preparedness, to political mobilization. 

PMID- 24098661
TI  - A three-marker FISH panel detects more genetic aberrations of AR, PTEN and
      TMPRSS2/ERG in castration-resistant or metastatic prostate cancers than in
      primary prostate tumors.
AB  - TMPRSS2/ERG rearrangement, PTEN gene deletion, and androgen receptor (AR) gene
      amplification have been observed in various stages of human prostate cancer. We
      hypothesized that using these markers as a combined panel would allow better
      differentiation between low-risk and high-risk prostate cancer. We analyzed 110
      primary prostate cancer samples, 70 metastatic tumor samples from 11 patients,
      and 27 xenograft tissues derived from 22 advanced prostate cancer patients using
      fluorescence in situ hybridization (FISH) analysis with probes targeting the
      TMPRSS2/ERG, PTEN, and AR gene loci. Heterogeneity of the aberrations detected
      was evaluated. Genetic patterns were also correlated with transcript levels.
      Among samples with complete data available, the three-marker FISH panel detected
      chromosomal abnormalities in 53% of primary prostate cancers and 87% of
      metastatic (Met) or castration-resistant (CRPC) tumors. The number of markers
      with abnormal FISH result had a different distribution between the two groups
      (P<0.001). At the patient level, Met/CRPC tumors are 4.5 times more likely to
      show abnormalities than primary cancer patients (P<0.05). Heterogeneity among
      Met/CRPC tumors is mostly inter-patient. Intra-patient heterogeneity is primarily
      due to differences between the primary prostate tumor and the metastases while
      multiple metastatic sites show consistent abnormalities. Intra-tumor variability
      is most prominent with the AR copy number in primary tumors. AR copy number
      correlated well with the AR mRNA expression (rho = 0.52, P<0.001). Especially
      among TMPRSS2:ERG fusion-positive CRPC tumors, AR mRNA and ERG mRNA levels are
      strongly correlated (rho = 0.64, P<0.001). Overall, the three-marker FISH panel
      may represent a useful tool for risk stratification of prostate cancer patients. 

PMID- 24098662
TI  - Loss of fibrinogen in zebrafish results in symptoms consistent with human
      hypofibrinogenemia.
AB  - Cessation of bleeding after trauma is a necessary evolutionary vertebrate
      adaption for survival. One of the major pathways regulating response to
      hemorrhage is the coagulation cascade, which ends with the cleavage of fibrinogen
      to form a stable clot. Patients with low or absent fibrinogen are at risk for
      bleeding. While much detailed information is known about fibrinogen regulation
      and function through studies of humans and mammalian models, bleeding risk in
      patients cannot always be accurately predicted purely based on fibrinogen levels,
      suggesting an influence of modifying factors and a need for additional genetic
      models. The zebrafish has orthologs to the three components of fibrinogen (fga,
      fgb, and fgg), but it hasn't yet been shown that zebrafish fibrinogen functions
      to prevent bleeding in vivo. Here we show that zebrafish fibrinogen is
      incorporated into an induced thrombus, and deficiency results in hemorrhage. An
      Fgb-eGFP fusion protein is incorporated into a developing thrombus induced by
      laser injury, but causes bleeding in adult transgenic fish. Antisense morpholino
      knockdown results in intracranial and intramuscular hemorrhage at 3 days post
      fertilization. The observed phenotypes are consistent with symptoms exhibited by
      patients with hypo- and afibrinogenemia. These data demonstrate that zebrafish
      possess highly conserved orthologs of the fibrinogen chains, which function
      similarly to mammals through the formation of a fibrin clot. 

PMID- 24098664
TI  - Survival analysis of irish amyotrophic lateral sclerosis patients diagnosed from
      1995-2010.
AB  - INTRODUCTION: The Irish ALS register is a valuable resource for examining
      survival factors in Irish ALS patients. Cox regression has become the default
      tool for survival analysis, but recently new classes of flexible parametric
      survival analysis tools known as Royston-Parmar models have become available.
      METHODS: We employed Cox proportional hazards and Royston-Parmar flexible
      parametric modeling to examine factors affecting survival in Irish ALS patients.
      We further examined the effect of choice of timescale on Cox models and the
      proportional hazards assumption, and extended both Cox and Royston-Parmar models
      with time varying components. RESULTS: On comparison of models we chose a Royston
      Parmar proportional hazards model without time varying covariates as the best
      fit. Using this model we confirmed the association of known survival markers in
      ALS including age at diagnosis (Hazard Ratio (HR) 1.34 per 10 year increase; 95%
      CI 1.26-1.42), diagnostic delay (HR 0.96 per 12 weeks delay; 95% CI 0.94-0.97),
      Definite ALS (HR 1.47 95% CI 1.17-1.84), bulbar onset disease (HR 1.58 95% CI
      1.33-1.87), riluzole use (HR 0.72 95% CI 0.61-0.85) and attendance at an ALS
      clinic (HR 0.74 95% CI 0.64-0.86). DISCUSSION: Our analysis explored the
      strengths and weaknesses of Cox proportional hazard and Royston-Parmar flexible
      parametric methods. By including time varying components we were able to gain
      deeper understanding of the dataset. Variation in survival between time periods
      appears to be due to missing data in the first time period. The use of age as
      timescale to account for confounding by age resolved breaches of the proportional
      hazards assumption, but in doing so may have obscured deficiencies in the data.
      Our study demonstrates the need to test for, and fully explore, breaches of the
      Cox proportional hazards assumption. Royston-Parmar flexible parametric modeling
      proved a powerful method for achieving this.

PMID- 24098663
TI  - PRMT5 is upregulated in malignant and metastatic melanoma and regulates
      expression of MITF and p27(Kip1.).
AB  - Protein arginine methyltransferase-5 (PRMT5) is a Type II arginine
      methyltransferase that regulates various cellular functions. We hypothesized that
      PRMT5 plays a role in regulating the growth of human melanoma cells.
      Immunohistochemical analysis indicated significant upregulation of PRMT5 in human
      melanocytic nevi, malignant melanomas and metastatic melanomas as compared to
      normal epidermis. Furthermore, nuclear PRMT5 was significantly decreased in
      metastatic melanomas as compared to primary cutaneous melanomas. In human
      metastatic melanoma cell lines, PRMT5 was predominantly cytoplasmic, and
      associated with its enzymatic cofactor Mep50, but not STAT3 or cyclin D1.
      However, histologic examination of tumor xenografts from athymic mice revealed
      heterogeneous nuclear and cytoplasmic PRMT5 expression. Depletion of PRMT5 via
      siRNA inhibited proliferation in a subset of melanoma cell lines, while it
      accelerated growth of others. Loss of PRMT5 also led to reduced expression of
      MITF (microphthalmia-associated transcription factor), a melanocyte-lineage
      specific oncogene, and increased expression of the cell cycle regulator
      p27(Kip1). These results are the first to report elevated PRMT5 expression in
      human melanoma specimens and indicate this protein may regulate MITF and
      p27(Kip1) expression in human melanoma cells. 

PMID- 24098665
TI  - Phonetic imitation from an individual-difference perspective: subjective
      attitude, personality and "autistic" traits.
AB  - Numerous studies have documented the phenomenon of phonetic imitation: the
      process by which the production patterns of an individual become more similar on
      some phonetic or acoustic dimension to those of her interlocutor. Though social
      factors have been suggested as a motivator for imitation, few studies has
      established a tight connection between language-external factors and a speaker's
      likelihood to imitate. The present study investigated the phenomenon of phonetic
      imitation using a within-subject design embedded in an individual-differences
      framework. Participants were administered a phonetic imitation task, which
      included two speech production tasks separated by a perceptual learning task, and
      a battery of measures assessing traits associated with Autism-Spectrum Condition,
      working memory, and personality. To examine the effects of subjective attitude on
      phonetic imitation, participants were randomly assigned to four experimental
      conditions, where the perceived sexual orientation of the narrator (homosexual
      vs. heterosexual) and the outcome (positive vs. negative) of the story depicted
      in the exposure materials differed. The extent of phonetic imitation by an
      individual is significantly modulated by the story outcome, as well as by the
      participant's subjective attitude toward the model talker, the participant's
      personality trait of openness and the autistic-like trait associated with
      attention switching.

PMID- 24098666
TI  - Cold temperatures increase cold hardiness in the next generation Ophraella
      communa beetles.
AB  - The leaf beetle, Ophraella communa, has been introduced to control the spread of
      the common ragweed, Ambrosia artemisiifolia, in China. We hypothesized that the
      beetle, to be able to track host-range expansion into colder climates, can
      phenotypically adapt to cold temperatures across generations. Therefore, we
      questioned whether parental experience of colder temperatures increases cold
      tolerance of the progeny. Specifically, we studied the demography, including
      development, fecundity, and survival, as well as physiological traits, including
      supercooling point (SCP), water content, and glycerol content of O. communa
      progeny whose parents were maintained at different temperature regimes. Overall,
      the entire immature stage decreased survival of about 0.2%-4.2% when parents
      experienced cold temperatures compared to control individuals obtained from
      parents raised at room temperature. However, intrinsic capacity for increase (r),
      net reproductive rate (R 0) and finite rate of increase (lambda) of progeny O.
      communa were maximum when parents experienced cold temperatures. Glycerol
      contents of both female and male in progeny was significantly higher when
      maternal and paternal adults were cold acclimated as compared to other
      treatments. This resulted in the supercooling point of the progeny adults being
      significantly lower compared to beetles emerging from parents that experienced
      room temperatures. These results suggest that cold hardiness of O. communa can be
      promoted by cold acclimation in previous generation, and it might counter-balance
      reduced survival in the next generation, especially when insects are tracking
      their host-plants into colder climates. 

PMID- 24098667
TI  - Association of survivin polymorphisms with tumor susceptibility: a meta-analysis.
AB  - BACKGROUND: The survivin polymorphisms have been shown to confer genetic
      susceptibility to various tumors, but the results are inconsistent. In order to
      accomplish a more precise estimation of the relationship, a meta-analysis was
      performed. RESULTS: For rs9904341, a significantly increased tumor risk was found
      in overall meta-analysis under C/C vs. G/G (OR = 1.40, 95% CI = 1.13-1.74, p =
      0.002), dominant (OR = 1.18, 95% CI = 1.01-1.38, p = 0.039) and recessive (OR =
      1.34, 95% CI = 1.13-1.58, p = 0.001) genetic models and Asians group. In subgroup
      analyses of tumor types, we found a significant association between this SNP and
      an increased risk of gastric, colorectal, bladder and other tumors as well as a
      decreased risk of hepatocellular cancer. For rs17878467, a significantly
      decreased tumor risk was identified in overall meta-analysis for allele contrast
      (T vs. C: OR = 0.69, 95% CI = 0.51-0.92, p = 0.012), C/T vs. C/C (OR = 0.61, 95%
      CI = 0.42-0.88, p = 0.009) and dominant (OR = 0.62, 95% CI = 0.43-0.88, p =
      0.007) genetic models and Asians group. For rs2071214, we found a significant
      association between this SNP and an increased tumor risk in overall meta-analysis
      under G/G vs. A/A (OR = 1.51, 95% CI = 1.04-2.18, p = 0.029) and recessive (OR =
      1.54, 95% CI = 1.07-2.22, p = 0.020) genetic models and Asians group. Besides,
      there was a significant association of rs8073069 with an increased tumor risk
      under recessive genetic model (OR = 1.37, 95% CI = 1.01-1.84, p = 0.040), while
      no significant association between rs1042489 and tumor risk was detected.
      CONCLUSIONS: The survivin rs9904341 most likely contributed to increased
      susceptibility to tumor in Asians as well as to gastric, colorectal and bladder
      cancers. As for rs17878467, the T allele might be a protective factor for tumor,
      especially in Asians. Moreover, the survivin rs8073069 and rs2071214 seemed to be
      associated with an increased tumor risk in Asians, while there was no association
      between the survivin rs1042489 and tumor risk.

PMID- 24098668
TI  - Small angle X-ray scattering studies of mitochondrial glutaminase C reveal
      extended flexible regions, and link oligomeric state with enzyme activity.
AB  - Glutaminase C is a key metabolic enzyme, which is unregulated in many cancer
      systems and believed to play a central role in the Warburg effect, whereby cancer
      cells undergo changes to an altered metabolic profile. A long-standing hypothesis
      links enzymatic activity to the protein oligomeric state, hence the study of the
      solution behavior in general and the oligomer state in particular of glutaminase
      C is important for the understanding of the mechanism of protein activation and
      inhibition. In this report, this is extensively investigated in correlation to
      enzyme concentration or phosphate level, using a high-throughput microfluidic
      mixing chip for the SAXS data collection, and we confirm that the oligomeric
      state correlates with activity. The in-depth solution behavior analysis further
      reveals the structural behavior of flexible regions of the protein in the
      dimeric, tetrameric and octameric state and investigates the C-terminal influence
      on the enzyme solution behavior. Our data enable SAXS-based rigid body modeling
      of the full-length tetramer states, thereby presenting the first ever
      experimentally derived structural model of mitochondrial glutaminase C including
      the N- and C-termini of the enzyme. 

PMID- 24098669
TI  - Validation of the German version of the patient activation measure 13 (PAM13-D)
      in an international multicentre study of primary care patients.
AB  - The patients' active participation in their medical care is important for
      patients with chronic diseases. Measurements of patient activation are needed for
      studies and in clinical practice. This study aims to validate the Patient
      Activation Measure 13 (PAM13-D) in German-speaking primary care patients. This
      international cross-sectional multicentre study enrolled consecutively patients
      from primary care practices in three German-speaking countries: Germany, Austria,
      and Switzerland. Patients completed the PAM13-D questionnaire. General Self
      Efficacy scale (GSE) was used to assess convergent validity. Furthermore
      Cronbach's alpha was performed to assess internal consistency. Exploratory factor
      analysis was used to evaluate the underlying factor structure of the items. We
      included 508 patients from 16 primary care practices in the final analysis.
      Results were internally consistent, with a Cronbach's alpha of 0.84. Factor
      analysis revealed one major underlying factor. The mean values of the PAM13-D
      correlated significantly (r = 0.43) with those of the GSE. The German PAM13 is a
      reliable and valid measure of patient activation. Thus, it may be useful in
      primary care clinical practice and research. 

PMID- 24098670
TI  - In vivo manipulation of gamma9(+) T cells in the common marmoset (Callithrix
      Jacchus) with phosphoantigen and effect on the progression of respiratory
      melioidosis.
AB  - Burkholderia pseudomallei is a dangerous human pathogen. Phosphoantigens
      specifically the target primate specific gamma9(+)delta2(+) T cells subset and
      some have been developed as potential immunotherapeutics. Previously, we
      demonstrated that, when stimulated with the phosphoantigen CHDMAPP,
      gamma9(+)delta2(+) T cells aid in the killing of intracellular B. pseudomallei
      bacteria. Moreover, we found that common marmoset (Callithrix Jacchus) gamma9(+)
      T cells increase in frequency and respond to the phosphoantigen CHDMAPP and/or B.
      pseudomallei, in combination with IL-2, in a similar manner to human
      gamma9(+)delta2(+) T cells. Here we evaluate the efficacy of the phosphoantigen
      CHDMAPP, in combination with IL-2, as a therapy against B. pseudomallei
      infection, in vivo. We found that the previous studies predicted the in vivo
      responsiveness of gamma9(+) T cells to the CHDMAPP+IL-2 treatment and significant
      expansion of the numbers of peripheral and splenic gamma9(+) T cells were
      observed. This effect was similar to those reported in other primate species
      treated with phosphoantigen. Furthermore, splenocytes were retrieved 7 days post
      onset of treatment, restimulated with CHDMAPP or heat-killed B. pseudomallei and
      the cultured gamma9(+) T cells demonstrated no reduction in IFN-gamma response
      when CHDMAPP+IL-2 animals were compared to IL-2 only treated animals. Using an
      established model of B. pseudomallei infection in the marmoset, we assessed the
      potential for using phosphoantigen as a novel immunotherapy. The CHDMAPP
      treatment regime had no effect on the progression of respiratory melioidosis and
      this was despite the presence of elevated numbers of gamma9(+) T cells in the
      spleen, liver and lung and an increased proportion of IFN-gamma(+) cells in
      response to infection. We therefore report that the common marmoset has proven a
      good model for studying the effect in vivo of gamma9(+) T cell stimulation;
      however, gamma9(+) T cells have little or no effect on the progression of lethal,
      respiratory B. pseudomallei infection. 

PMID- 24098671
TI  - Haplotype variation of Glu-D1 locus and the origin of Glu-D1d allele conferring
      superior end-use qualities in common wheat.
AB  - In higher plants, seed storage proteins (SSPs) are frequently expressed from
      complex gene families, and allelic variation of SSP genes often affects the
      quality traits of crops. In common wheat, the Glu-D1 locus, encoding 1Dx and 1Dy
      SSPs, has multiple alleles. The Glu-D1d allele frequently confers superior end
      use qualities to commercial wheat varieties. Here, we studied the haplotype
      structure of Glu-D1 genomic region and the origin of Glu-D1d. Using seven
      diagnostic DNA markers, 12 Glu-D1 haplotypes were detected among common wheat,
      European spelt wheat (T. spelta, a primitive hexaploid relative of common wheat),
      and Aegilops tauschii (the D genome donor of hexaploid wheat). By comparatively
      analyzing Glu-D1 haplotypes and their associated 1Dx and 1Dy genes, we deduce
      that the haplotype carrying Glu-D1d was likely differentiated in the ancestral
      hexaploid wheat around 10,000 years ago, and was subsequently transmitted to
      domesticated common wheat and T. spelta. A group of relatively ancient Glu-D1
      haplotypes was discovered in Ae. tauschii, which may serve for the evolution of
      other haplotypes. Moreover, a number of new Glu-D1d variants were found in T.
      spelta. The main steps in Glu-D1d differentiation are proposed. The implications
      of our work for enhancing the utility of Glu-D1d in wheat quality improvement and
      studying the SSP alleles in other crop species are discussed. 

PMID- 24098672
TI  - Drosophila morgue associates with SkpA and polyubiquitin in vivo.
AB  - Morgue is a unique ubiquitination protein that influences programmed cell death
      and circadian rhythms in Drosophila. We have found that over-expression of wild
      type Morgue results in organismal lethality. This over-expression phenotype was
      used as the basis for an in vivo functional assay to investigate the importance
      of the Morgue zinc finger, F box, Ubiquitin E2 Conjugase Variant (UEV) domain,
      and active site Glycine residue. Removal of the zinc finger or UEV domain reduced
      Morgue's ability to induce lethality and enhance cell death. In contrast, lack of
      the F box as well as several different substitutions of the active site Glycine
      did not alter Morgue-induced lethality or cell death enhancement. To further
      characterize Morgue functions, a Flag:Morgue protein was used to isolate Morgue
      associated proteins from whole adult Drosophila. Mass spectrometry analysis of
      the Morgue-associated proteins identified SkpA as well as a ubiquitin multimer.
      The identification of SkpA is consistent with previous in vitro studies and
      further suggests Morgue acts in an SCF-type ubiquitin E3 ligase complex. The
      identification of poly-ubiquitin was unexpected and this interaction had not been
      previously identified. The associated poly-ubiquitin was found to exhibit a Lys
      48 topology, consistent with distinct functions of Morgue in proteasome-mediated
      protein turnover. Multiple regions of Morgue were subsequently shown to be
      required for poly-ubiquitin binding. Overall, Morgue is a novel multi-functional
      ubiquitin-binding protein. 

PMID- 24098673
TI  - Functionally deregulated AML1/RUNX1 cooperates with BCR-ABL to induce a blastic
      phase-like phenotype of chronic myelogenous leukemia in mice.
AB  - Patients in the chronic phase (CP) of chronic myelogenous leukemia (CML) have
      been treated successfully following the advent of ABL kinase inhibitors, but once
      they progress to the blast crisis (BC) phase the prognosis becomes dismal.
      Although mechanisms underlying the progression are largely unknown, recent
      studies revealed the presence of alterations of key molecules for hematopoiesis,
      such as AML1/RUNX1. Our analysis of 13 BC cases revealed that three cases had
      AML1 mutations and the transcript levels of wild-type (wt.) AML1 were elevated in
      BC compared with CP. Functional analysis of representative AML1 mutants using
      mouse hematopoietic cells revealed the possible contribution of some, but not
      all, mutants for the BC-phenotype. Specifically, K83Q and R139G, but neither R80C
      nor D171N mutants, conferred upon BCR-ABL-expressing cells a growth advantage
      over BCR-ABL-alone control cells in cytokine-free culture, and the cells thus
      grown killed mice upon intravenous transfer. Unexpectedly, wt.AML1 behaved
      similarly to K83Q and R139G mutants. In a bone marrow transplantation assay, K83Q
      and wt.AML1s induced the emergence of blast-like cells. The overall findings
      suggest the roles of altered functions of AML1 imposed by some, but not all,
      mutants, and the elevated expression of wt.AML1 for the disease progression of
      CML. 

PMID- 24098674
TI  - Cluster analysis of clinical data identifies fibromyalgia subgroups.
AB  - INTRODUCTION: Fibromyalgia (FM) is mainly characterized by widespread pain and
      multiple accompanying symptoms, which hinder FM assessment and management. In
      order to reduce FM heterogeneity we classified clinical data into simplified
      dimensions that were used to define FM subgroups. MATERIAL AND METHODS: 48
      variables were evaluated in 1,446 Spanish FM cases fulfilling 1990 ACR FM
      criteria. A partitioning analysis was performed to find groups of variables
      similar to each other. Similarities between variables were identified and the
      variables were grouped into dimensions. This was performed in a subset of 559
      patients, and cross-validated in the remaining 887 patients. For each sample and
      dimension, a composite index was obtained based on the weights of the variables
      included in the dimension. Finally, a clustering procedure was applied to the
      indexes, resulting in FM subgroups. RESULTS: VARIABLES CLUSTERED INTO THREE
      INDEPENDENT DIMENSIONS: "symptomatology", "comorbidities" and "clinical scales".
      Only the two first dimensions were considered for the construction of FM
      subgroups. Resulting scores classified FM samples into three subgroups: low
      symptomatology and comorbidities (Cluster 1), high symptomatology and
      comorbidities (Cluster 2), and high symptomatology but low comorbidities (Cluster
      3), showing differences in measures of disease severity. CONCLUSIONS: We have
      identified three subgroups of FM samples in a large cohort of FM by clustering
      clinical data. Our analysis stresses the importance of family and personal
      history of FM comorbidities. Also, the resulting patient clusters could indicate
      different forms of the disease, relevant to future research, and might have an
      impact on clinical assessment.

PMID- 24098675
TI  - Alterations in the Helicoverpa armigera midgut digestive physiology after
      ingestion of pigeon pea inducible leucine aminopeptidase.
AB  - Jasmonate inducible plant leucine aminopeptidase (LAP) is proposed to serve as
      direct defense in the insect midgut. However, exact functions of inducible plant
      LAPs in the insect midgut remain to be estimated. In the present investigation,
      we report the direct defensive role of pigeon pea inducible LAP in the midgut of
      Helicoverpa armigera (Lepidoptera: Noctuidae) and responses of midgut soluble
      aminopeptidases and serine proteinases upon LAP ingestion. Larval growth and
      survival was significantly reduced on the diets supplemented with pigeon pea LAP.
      Aminopeptidase activities in larvae remain unaltered in presence or absence of
      inducible LAP in the diet. On the contrary, serine proteinase activities were
      significantly decreased in the larvae reared on pigeon pea LAP containing diet as
      compared to larvae fed on diet without LAP. Our data suggest that pigeon pea
      inducible LAP is responsible for the degradation of midgut serine proteinases
      upon ingestion. Reduction in the aminopeptidase activity with LpNA in the H.
      armigera larvae was compensated with an induction of aminopeptidase activity with
      ApNA. Our findings could be helpful to further dissect the roles of plant
      inducible LAPs in the direct plant defense against herbivory. 

PMID- 24098676
TI  - Relative contributions of norepinephrine and serotonin transporters to
      antinociceptive synergy between monoamine reuptake inhibitors and morphine in the
      rat formalin model.
AB  - Multimodal analgesia is designed to optimize pain relief by coadministering drugs
      with distinct mechanisms of action or by combining multiple pharmacologies within
      a single molecule. In clinical settings, combinations of monoamine reuptake
      inhibitors and opioid receptor agonists have been explored and one currently
      available analgesic, tapentadol, functions as both a u-opioid receptor agonist
      and a norepinephrine transporter inhibitor. However, it is unclear whether the
      combination of selective norepinephrine reuptake inhibition and u-receptor
      agonism achieves an optimal antinociceptive synergy. In this study, we assessed
      the pharmacodynamic interactions between morphine and monoamine reuptake
      inhibitors that possess different affinities and selectivities for norepinephrine
      and serotonin transporters. Using the rat formalin model, in conjunction with
      measurements of ex vivo transporter occupancy, we show that neither the
      norepinephrine-selective inhibitor, esreboxetine, nor the serotonin-selective
      reuptake inhibitor, fluoxetine, produce antinociceptive synergy with morphine.
      Atomoxetine, a monoamine reuptake inhibitor that achieves higher levels of
      norepinephrine than serotonin transporter occupancy, exhibited robust
      antinociceptive synergy with morphine. Similarly, a fixed-dose combination of
      esreboxetine and fluoxetine which achieves comparable levels of transporter
      occupancy potentiated the antinociceptive response to morphine. By contrast,
      duloxetine, a monoamine reuptake inhibitor that achieves higher serotonin than
      norepinephrine transporter occupancy, failed to potentiate the antinociceptive
      response to morphine. However, when duloxetine was coadministered with the 5-HT3
      receptor antagonist, ondansetron, potentiation of the antinociceptive response to
      morphine was revealed. These results support the notion that inhibition of both
      serotonin and norepinephrine transporters is required for monoamine reuptake
      inhibitor and opioid-mediated antinociceptive synergy; yet, excess serotonin,
      acting via 5-HT3 receptors, may reduce the potential for synergistic
      interactions. Thus, in the rat formalin model, the balance between norepinephrine
      and serotonin transporter inhibition influences the degree of antinociceptive
      synergy observed between monoamine reuptake inhibitors and morphine. 

PMID- 24098677
TI  - High genetic diversity and distinctiveness of rear-edge climate relicts
      maintained by ancient tetraploidisation for Alnus glutinosa.
AB  - Populations located at the rear-edge of a species' distribution may have
      disproportionate ecological and evolutionary importance for biodiversity
      conservation in a changing global environment. Yet genetic studies of such
      populations remain rare. This study investigates the evolutionary history of
      North-African low latitude marginal populations of Alnus glutinosa Gaertn., a
      European tree species that plays a significant ecological role as a keystone of
      riparian ecosystems. We genotyped 551 adults from 19 populations located across
      North Africa at 12 microsatellite loci and applied a coalescent-based simulation
      approach to reconstruct the demographic and evolutionary history of these
      populations. Surprisingly, Moroccan trees were tetraploids demonstrating a strong
      distinctiveness of these populations within a species otherwise known as diploid.
      Best-fitting models of demographic reconstruction revealed the relict nature of
      Moroccan populations that were found to have withstood past climate change events
      and to be much older than Algerian and Tunisian populations. This study
      highlights the complex demographic history that can be encountered in rear-edge
      distribution margins that here consist of both old stable climate relict and more
      recent populations, distinctively diverse genetically both quantitatively and
      qualitatively. We emphasize the high evolutionary and conservation value of
      marginal rear-edge populations of a keystone riparian species in the context of
      on-going climate change in the Mediterranean region. 

PMID- 24098678
TI  - Long term evaluation of the impact of autologous peripheral blood stem cell
      transplantation in multiple myeloma: a cost-effectiveness analysis.
AB  - BACKGROUND: High-dose therapy with autologous peripheral stem cell
      transplantation represents today the standard approach for younger multiple
      myeloma patients. This study aimed to evaluate the long term economic impact of
      autologous transplantation with respect to conventional therapy. METHODS: We
      retrospectively reviewed the charts of multiple myeloma patients diagnosed at our
      department between 1986 and 2003 and treated according to the therapy considered
      standard at the time of diagnosis. Analysis of costs was done by assessing
      resource utilization and direct costs were measured and monetized before
      proceeding with the analysis, based on public health service tariffs. RESULTS:
      Group A including 78 patients treated with Melphalan and Prednisone was compared
      with Group B including 74 patients who received an autologous transplant. The
      median overall survival was 3.2 and 5.4 years respectively (p = 0.0002). Mean
      cost per patient was significantly higher in group B with respect to group A
      (102373? vs 23825?; p<0.001). The final quality-adjusted-life-year gain in group
      B patients as compared to group A was 1.73 QALY, with an incremental cost
      effectiveness ratio of 45460?. With a threshold of 75000? per QALY gained, the
      cost effectiveness acceptability curve indicated that the probability that
      autologous transplantation in multiple myeloma is a cost-effective intervention
      is 90%. CONCLUSIONS: The cost of autologous transplantation remains high. The
      calculated incremental cost-effectiveness ratio, however, given the significant
      prolongation of overall survival obtained with autologous transplantation, is
      within an acceptable threshold. Notwithstanding, its high cost should be taken
      into account when considering the whole cost of multiple myeloma.

PMID- 24098679
TI  - Accumulating mutations in series of haplotypes at the KIT and MITF loci are major
      determinants of white markings in Franches-Montagnes horses.
AB  - Coat color and pattern variations in domestic animals are frequently inherited as
      simple monogenic traits, but a number are known to have a complex genetic basis.
      While the analysis of complex trait data remains a challenge in all species, we
      can use the reduced haplotypic diversity in domestic animal populations to gain
      insight into the genomic interactions underlying complex phenotypes. White face
      and leg markings are examples of complex traits in horses where little is known
      of the underlying genetics. In this study, Franches-Montagnes (FM) horses were
      scored for the occurrence of white facial and leg markings using a standardized
      scoring system. A genome-wide association study (GWAS) was performed for several
      white patterning traits in 1,077 FM horses. Seven quantitative trait loci (QTL)
      affecting the white marking score with p-values p<=10(-4) were identified. Three
      loci, MC1R and the known white spotting genes, KIT and MITF, were identified as
      the major loci underlying the extent of white patterning in this breed. Together,
      the seven loci explain 54% of the genetic variance in total white marking score,
      while MITF and KIT alone account for 26%. Although MITF and KIT are the major
      loci controlling white patterning, their influence varies according to the basic
      coat color of the horse and the specific body location of the white patterning.
      Fine mapping across the MITF and KIT loci was used to characterize haplotypes
      present. Phylogenetic relationships among haplotypes were calculated to assess
      their selective and evolutionary influences on the extent of white patterning.
      This novel approach shows that KIT and MITF act in an additive manner and that
      accumulating mutations at these loci progressively increase the extent of white
      markings. 

PMID- 24098680
TI  - Mice lacking the p43 mitochondrial T3 receptor become glucose intolerant and
      insulin resistant during aging.
AB  - Thyroid hormones (TH) play an important regulatory role in energy expenditure
      regulation and are key regulators of mitochondrial activity. We have previously
      identified a mitochondrial triiodothyronine (T3) receptor (p43) which acts as a
      mitochondrial transcription factor of the organelle genome, which leads in vitro
      and in vivo, to a stimulation of mitochondrial biogenesis. Recently, we generated
      mice carrying a specific p43 invalidation. At 2 months of age, we reported that
      p43 depletion in mice induced a major defect in insulin secretion both in vivo
      and in isolated pancreatic islets, and a loss of glucose-stimulated insulin
      secretion. The present study was designed to determine whether p43 invalidation
      influences life expectancy and modulates blood glucose and insulin levels as well
      as glucose tolerance or insulin sensitivity during aging. We report that from 4
      months old onwards, mice lacking p43 are leaner than wild-type mice. p43-/- mice
      also have a moderate reduction of life expectancy compared to wild type. We found
      no difference in blood glucose levels, excepted at 24 months old where p43-/-
      mice showed a strong hyperglycemia in fasting conditions compared to controls
      animals. However, the loss of glucose-stimulated insulin secretion was maintained
      whatever the age of mice lacking p43. If up to 12 months old, glucose tolerance
      remained unchanged, beyond this age p43-/- mice became increasingly glucose
      intolerant. In addition, if up to 12 months old p43 deficient animals were more
      sensitive to insulin, after this age we observed a loss of this capacity,
      culminating in 24 months old mice with a decreased sensitivity to the hormone. In
      conclusion, we demonstrated that during aging the depletion of the mitochondrial
      T3 receptor p43 in mice progressively induced an increased glycemia in the fasted
      state, glucose intolerance and an insulin-resistance several features of type-2
      diabetes. 

PMID- 24098681
TI  - Increased protein stability of CDKN1C causes a gain-of-function phenotype in
      patients with IMAGe syndrome.
AB  - Mutations in the proliferating cell nuclear antigen (PCNA)-binding domain of the
      CDKN1C gene were recently identified in patients with IMAGe syndrome. However,
      loss of PCNA binding and suppression of CDKN1C monoubiquitination by IMAGe
      associated mutations hardly explain the reduced-growth phenotype characteristic
      of IMAGe syndrome. We demonstrate here that IMAGe-associated mutations in the
      CDKN1C gene dramatically increased the protein stability. We identified a novel
      heterozygous mutation, c.815T>G (p.Ile272Ser), in the CDKN1C gene in three
      siblings manifesting clinical symptoms associated with IMAGe syndrome and their
      mother (unaffected carrier). PCNA binding to CDKN1C was disrupted in the case of
      p.Ile272Ser, and for two other IMAGe-associated mutations, p.Asp274Asn and
      p.Phe276Val. Intriguingly, the IMAGe-associated mutant CDKN1C proteins were
      fairly stable even in the presence of cycloheximide, whereas the wild-type
      protein was almost completely degraded via the proteasome pathway, as shown by
      the lack of degradation with addition of a proteasome inhibitor, MG132. These
      results thus suggested that the reduced-growth phenotype of IMAGe syndrome
      derives from CDKN1C gain-of-function due to IMAGe-associated mutations driving
      increased protein stability. 

PMID- 24098682
TI  - Dietary oleic acid increases m2 macrophages in the mesenteric adipose tissue.
AB  - Several studies have implicated fatty-acids as inflammatory regulators,
      suggesting that there may be a direct role for common dietary fatty-acids in
      regulating innate immune cells. In humans, a single high-fat meal increases
      systemic cytokines and leukocytes. In mice, short term high-fat feeding increases
      adipose tissue (AT) leukocytes and alters the inflammatory profile of AT
      macrophages. We have seen that short term high fat feeding to C57BL/6J male mice
      increases palmitic and oleic acid within AT depots, but oleic acid increase is
      highest in the mesenteric AT (MAT). In vitro, oleic acid increases M2 macrophage
      markers (CD206, MGL1, and ARG1) in a murine macrophage cell line, while addition
      of palmitic acid is able to inhibit that increase. Three day supplementation of a
      chow diet, with oleic acid, induced an increase in M2 macrophage markers in the
      MAT, but not in the epididymal AT. We tested whether increases in M2 macrophages
      occur during short term ad lib feeding of a high fat diet, containing oleic acid.
      Experiments revealed two distinct populations of macrophages were altered by a
      three day high milk-fat diet. One population, phenotypically intermediate for
      F4/80, showed diet-induced increases in CD206, an anti-inflammatory marker
      characteristic of M2 macrophages intrinsic to the AT. Evidence for a second
      population, phenotypically F4/80(HI)CD11b(HI) macrophages, showed increased
      association with the MAT following short term feeding that is dependent on the
      adhesion molecule, ICAM-1. Collectively, we have shown that short term feeding of
      a high-fat diet changes two population of macrophages, and that dietary oleic
      acid is responsible for increases in M2 macrophage polarization. 

PMID- 24098683
TI  - Non-Hodgkin lymphoma risk and variants in genes controlling lymphocyte
      development.
AB  - Non-Hodgkin lymphomas (NHL) are a heterogeneous group of solid tumours of
      lymphoid cell origin. Three important aspects of lymphocyte development include
      immunity and inflammation, DNA repair, and programmed cell death. We have used a
      previously established case-control study of NHL to ask whether genetic variation
      in genes involved in these three important processes influences risk of this
      cancer. 118 genes in these three categories were tagged with single nucleotide
      polymorphisms (SNPs), which were tested for association with NHL and its
      subtypes. The main analysis used logistic regression (additive model) to estimate
      odds ratios in European-ancestry cases and controls. 599 SNPs and 1116 samples
      (569 cases and 547 controls) passed quality control measures and were included in
      analyses. Following multiple-testing correction, one SNP in MSH3, a mismatch
      repair gene, showed an association with diffuse large B-cell lymphoma (OR: 1.91;
      95% CI: 1.41-2.59; uncorrected p = 0.00003; corrected p = 0.010). This
      association was not replicated in an independent European-ancestry sample set of
      251 diffuse large B-cell lymphoma cases and 737 controls, indicating this result
      was likely a false positive. It is likely that moderate sample size, inter
      subtype and other genetic heterogeneity, and small true effect sizes account for
      the lack of replicable findings. 

PMID- 24098684
TI  - A collection of primary tissue cultures of tumors from vacuum packed and cooled
      surgical specimens: a feasibility study.
AB  - Primary cultures represent an invaluable tool to set up functional experimental
      conditions; however, creation of tissue cultures from solid tumors is troublesome
      and often unproductive. Several features can affect the success rate of primary
      cultures, including technical issues from pre-analytical procedures employed in
      surgical theaters and pathology laboratories. We have recently introduced a new
      method of collection, transfer, and preservation of surgical specimens that
      requires immediate vacuum sealing of excised specimens at surgical theaters,
      followed by time-controlled transferring at 4 degrees C to the pathology
      laboratory. Here we investigate the feasibility and performance of short-term
      primary cell cultures derived from vacuum packed and cooled (VPAC) preserved
      tissues. Tissue fragments were sampled from 52 surgical specimens of tumors
      larger than 2 cm for which surgical and VPAC times (the latter corresponding to
      cold ischemia time) were recorded. Cell viability was determined by trypan blue
      dye-exclusion assay and hematoxylin and eosin and immunohistochemical stainings
      were performed to appreciate morphological and immunophenotypical features of
      cultured cells. Cell viability showed a range of 84-100% in 44 out of 52 (85%)
      VPAC preserved tissues. Length of both surgical and VPAC times affected cell
      viability: the critical surgical time was set around 1 hour and 30 minutes, while
      cells preserved a good viability when kept for about 24 hours of vacuum at 4
      degrees C. Cells were maintained in culture for at least three passages.
      Immunocytochemistry confirmed the phenotype of distinct populations, that is,
      expression of cytokeratins in epithelioid cells and of vimentin in spindle cells.
      Our results suggest that VPAC preserved tissues may represent a reliable source
      for creation of primary cell cultures and that a careful monitoring of surgical
      and cold ischemia times fosters a good performance of primary tissue cultures. 

PMID- 24098685
TI  - The heteromultimeric debranching enzyme involved in starch synthesis in
      Arabidopsis requires both isoamylase1 and isoamylase2 subunits for complex
      stability and activity.
AB  - Isoamylase-type debranching enzymes (ISAs) play an important role in determining
      starch structure. Amylopectin - a branched polymer of glucose - is the major
      component of starch granules and its architecture underlies the semi-crystalline
      nature of starch. Mutants of several species lacking the ISA1-subclass of
      isoamylase are impaired in amylopectin synthesis. Consequently, starch levels are
      decreased and an aberrant soluble glucan (phytoglycogen) with altered branch
      lengths and branching pattern accumulates. Here we use TAP (tandem affinity
      purification) tagging to provide direct evidence in Arabidopsis that ISA1
      interacts with its homolog ISA2. No evidence for interaction with other starch
      biosynthetic enzymes was found. Analysis of the single mutants shows that each
      protein is destabilised in the absence of the other. Co-expression of both ISA1
      and ISA2 Escherichia coli allowed the formation of the active recombinant enzyme
      and we show using site-directed mutagenesis that ISA1 is the catalytic subunit.
      The presence of the active isoamylase alters glycogen biosynthesis in E. coli,
      resulting in colonies that stain more starch-like with iodine. However, analysis
      of the glucans reveals that rather than producing an amylopectin like substance,
      cells expressing the active isoamylase still accumulate small amounts of glycogen
      together with a population of linear oligosaccharides that stain strongly with
      iodine. We conclude that for isoamylase to promote amylopectin synthesis it needs
      to act on a specific precursor (pre-amylopectin) generated by the combined
      actions of plant starch synthase and branching enzyme isoforms and when presented
      with an unsuitable substrate (i.e. E. coli glycogen) it simply degrades it. 

PMID- 24098686
TI  - Elevated serum ferritin level is associated with the incident type 2 diabetes in
      healthy Korean men: a 4 year longitudinal study.
AB  - BACKGROUND: Elevated ferritin concentration has been implicated in the etiology
      of type 2 diabetes. Accumulating evidence, mostly from studies conducted on
      western populations, has demonstrated a strong association between the elevated
      ferritin concentrations and incident type 2 diabetes. In Asian populations,
      however, the longitudinal studies investigating the association of elevated serum
      ferritin levels and type 2 diabetes are lacking. In present study, we aimed to
      determine whether elevated serum ferritin levels are related to the incident type
      2 diabetes in healthy Korean men. METHODOLOGY/PRINCIPAL FINDINGS: This 4 year
      longitudinal observational study was conducted at the Asan Medical Center, Seoul,
      Republic of Korea. The study population consisted of 2,029 men without type 2
      diabetes who underwent routine health examination in 2007 (baseline) and 2011
      (follow-up). Baseline serum ferritin concentrations were measured by
      chemiluminescent two-site sandwich immunoassay. In multiple-adjusted model, the
      relative risk (RR) for incident type 2 diabetes was significantly higher in
      highest compared with the lowest ferritin quartile category, even after adjusting
      for confounding variables including homeostasis model assessment of insulin
      resistance (RR = 2.17, 95% confidence interval 1.27-3.72, P for trend = 0.013).
      CONCLUSIONS/SIGNIFICANCE: These results demonstrated that elevated level of serum
      ferritin at baseline was associated with incident type 2 diabetes in an Asian
      population.

PMID- 24098687
TI  - Fluorescence characterization of clinically-important bacteria.
AB  - Healthcare-associated infections (HCAI/HAI) represent a substantial threat to
      patient health during hospitalization and incur billions of dollars additional
      cost for subsequent treatment. One promising method for the detection of
      bacterial contamination in a clinical setting before an HAI outbreak occurs is to
      exploit native fluorescence of cellular molecules for a hand-held, rapid-sweep
      surveillance instrument. Previous studies have shown fluorescence-based detection
      to be sensitive and effective for food-borne and environmental microorganisms,
      and even to be able to distinguish between cell types, but this powerful
      technique has not yet been deployed on the macroscale for the primary
      surveillance of contamination in healthcare facilities to prevent HAI. Here we
      report experimental data for the specification and design of such a fluorescence
      based detection instrument. We have characterized the complete fluorescence
      response of eleven clinically-relevant bacteria by generating excitation-emission
      matrices (EEMs) over broad wavelength ranges. Furthermore, a number of surfaces
      and items of equipment commonly present on a ward, and potentially responsible
      for pathogen transfer, have been analyzed for potential issues of background
      fluorescence masking the signal from contaminant bacteria. These include bedside
      handrails, nurse call button, blood pressure cuff and ward computer keyboard, as
      well as disinfectant cleaning products and microfiber cloth. All examined
      bacterial strains exhibited a distinctive double-peak fluorescence feature
      associated with tryptophan with no other cellular fluorophore detected. Thus,
      this fluorescence survey found that an emission peak of 340nm, from an excitation
      source at 280nm, was the cellular fluorescence signal to target for detection of
      bacterial contamination. The majority of materials analysed offer a spectral
      window through which bacterial contamination could indeed be detected. A few
      instances were found of potential problems of background fluorescence masking
      that of bacteria, but in the case of the microfiber cleaning cloth, imaging
      techniques could morphologically distinguish between stray strands and bacterial
      contamination. 

PMID- 24098688
TI  - Brain structural alterations in obsessive-compulsive disorder patients with
      autogenous and reactive obsessions.
AB  - Obsessive-compulsive disorder (OCD) is a clinically heterogeneous condition.
      Although structural brain alterations have been consistently reported in OCD,
      their interaction with particular clinical subtypes deserves further examination.
      Among other approaches, a two-group classification in patients with autogenous
      and reactive obsessions has been proposed. The purpose of the present study was
      to assess, by means of a voxel-based morphometry analysis, the putative brain
      structural correlates of this classification scheme in OCD patients. Ninety-five
      OCD patients and 95 healthy controls were recruited. Patients were divided into
      autogenous (n = 30) and reactive (n = 65) sub-groups. A structural magnetic
      resonance image was acquired for each participant and pre-processed with SPM8
      software to obtain a volume-modulated gray matter map. Whole-brain and voxel-wise
      comparisons between the study groups were then performed. In comparison to the
      autogenous group, reactive patients showed larger gray matter volumes in the
      right Rolandic operculum. When compared to healthy controls, reactive patients
      showed larger volumes in the putamen (bilaterally), while autogenous patients
      showed a smaller left anterior temporal lobe. Also in comparison to healthy
      controls, the right middle temporal gyrus was smaller in both patient subgroups.
      Our results suggest that autogenous and reactive obsessions depend on partially
      dissimilar neural substrates. Our findings provide some neurobiological support
      for this classification scheme and contribute to unraveling the neurobiological
      basis of clinical heterogeneity in OCD. 

PMID- 24098689
TI  - Parity and risk of colorectal cancer: a dose-response meta-analysis of
      prospective studies.
AB  - BACKGROUND: Association between parity and colorectal cancer (CRC) risk has been
      investigated by several epidemiological studies but results are controversial,
      yet a comprehensive and quantitative assessment of this association has not been
      reported so far. METHODS: Relevant published studies of parity and CRC were
      identified using MEDLINE, EMBASE and Web of Science databases through end of
      April 2013. Two authors independently assessed eligibility and extracted data.
      Eleven prospective studies reported relative risk (RR) estimates and 95%
      confidence intervals (CIs) of CRC risk associated with parity. We pooled the RR
      from individual studies using fixed- or random-effects models and carried out
      heterogeneity and publication bias analyses. RESULTS: The summary RR for the ever
      parity vs. nulliparous was 0.95 (95% CI: 0.88-1.02), with no heterogeneity (Q =
      9.04, P = 0.443, I (2) = 0.5%). Likewise, no significant association was yielded
      for the highest vs. lowest parity number (RR = 1.02, 95% CI: 0.89-1.17), with
      moderate heterogeneity (Q = 17.48, P = 0.094, I (2) = 37.1%). Dose-response
      analysis still indicated no effect of parity on CRC risk and the summary RR of
      per one livebirth was 0.99 (95% CI: 0.96-1.02), with moderate of heterogeneity (Q
      = 16.50, P<0.021, I (2) = 57.6%). Similar results were observed among all the
      subgroup analyses. No evidence of publication bias and significant heterogeneity
      between subgroups were detected by meta-regression analyses. CONCLUSION: Results
      of this dose-response meta-analysis of prospective studies found that there was
      little evidence of an association between parity and CRC risk.

PMID- 24098691
TI  - To feed or not to feed: plant factors located in the epidermis, mesophyll, and
      sieve elements influence pea aphid's ability to feed on legume species.
AB  - The pea aphid (Acyrthosiphon pisum Harris), a legume specialist, encompasses at
      least 11 genetically distinct sympatric host races. Each host race shows a
      preference for a certain legume species. Six pea aphid clones from three host
      races were used to localize plant factors influencing aphid probing and feeding
      behavior on four legume species. Aphid performance was tested by measuring
      survival and growth. The location of plant factors influencing aphid probing and
      feeding was determined using the electrical penetration graph (EPG) technique.
      Every aphid clone performed best on the plant species from which it was
      originally collected, as well as on Vicia faba. On other plant species, clones
      showed intermediate or poor performance. The most important plant factors
      influencing aphid probing and feeding behavior were localized in the epidermis
      and sieve elements. Repetitive puncturing of sieve elements might be relevant for
      establishing phloem feeding, since feeding periods appear nearly exclusively
      after these repetitive sieve element punctures. A combination of plant factors
      influences the behavior of pea aphid host races on different legume species and
      likely contributes to the maintenance of these races. 

PMID- 24098690
TI  - Genetic polymorphism of angiotensin converting enzyme and risk of coronary
      restenosis after percutaneous transluminal coronary angioplasties: evidence from
      33 cohort studies.
AB  - BACKGROUND: In the past decade, a number of cohort studies studies have been
      carried out to investigate the relationship between the insertion/deletion
      polymorphism of the gene encoding angiotensin-converting enzyme and risk of
      restenosis after percutaneous transluminal coronary angioplasties in patients.
      However, these studies have yielded contradictory results. Genetic association
      studies addressing this issue are frequently hampered by insufficient power. We
      therefore performed a meta-analysis of the published studies to clarify this
      inconsistency and to establish a comprehensive picture of the relationship
      between ACE I/D polymorphism and post-PTCA restenosis risk. METHODS: Databases
      including Pubmed, EMBASE, ISI Web of Science, EBSCO, Cochrane Library databases
      and CNKI were searched to find relevant studies. Odds ratios (ORs) with 95%
      confidence intervals (CIs) were used to assess the strength of association. The
      random-effects model was applied, addressing heterogeneity and publication bias.
      RESULTS: A total of 33 cohort studies involving 11,099 subjects were included. In
      a combined analysis, the OR for post-PTCA restenosis of the ACE DD genotype was
      1.61 (95% CI: 1.27-2.04; P<10(-5)). In the subgroup analysis by intervention,
      significantly increased risks were also found in PTCA-stent and PTCA-balloon for
      the DD genotype of the polymorphism. CONCLUSIONS: Our meta-analysis showed that
      the DD genotype of ACE I/D polymorphism was significantly associated with
      increased risk of restenosis, particularly for PTCA-stent.

PMID- 24098692
TI  - Unintended pregnancy among HIV positive couples receiving integrated HIV
      counseling, testing, and family planning services in Zambia.
AB  - OBJECTIVE: We describe rates of unintended pregnancy among HIV positive couples
      in Lusaka, Zambia. We also identify factors associated with unintended pregnancy
      among oral contraceptive pill (OCP) using couples in this cohort. DESIGN: Data
      were analyzed from couples randomized in a factorial design to two family
      planning intervention videos. METHODS: Rates of unintended pregnancy were
      stratified by contraceptive method used at time of pregnancy. Predictors of time
      to unintended pregnancy among OCP users were determined via multivariate Cox
      modeling. RESULTS: The highest rates of unintended pregnancy were observed among
      couples requesting condoms only (26.4/100CY) or OCPs (20.7/100CY); these rates
      were not significantly different. OCP users accounted for 37% of the couple-years
      (CY) observed and 87% of unintended pregnancies. Rates of unintended pregnancy
      for injectable (0.7/100CY) and intrauterine device (1.6/100CY) users were
      significantly lower relative to condom only users. No pregnancies occurred among
      contraceptive implant users or after tubal ligation. Factors associated (p<0.05)
      with time to unintended pregnancy among OCP users in multivariate analysis
      included the man wanting more children, the woman being HIV negative versus
      having stage IV HIV disease, and the woman reporting: younger age, no previous
      OCP use, missed OCPs, or sex without a condom. CONCLUSIONS: Long-acting
      reversible contraceptive methods were effective in the context of integrated
      couples HIV prevention and contraceptive services. Injectable methods were also
      effective in this context. Given the high user failure rate of OCPs, family
      planning efforts should promote longer-acting methods among OCP users wishing to
      avoid pregnancy. Where other methods are not available or acceptable, OCP
      adherence counseling is needed, especially among younger and new OCP users. TRIAL
      REGISTRATION: ClinicalTrials.gov NCT00067522.

PMID- 24098693
TI  - Die Fledermaus: regarding optokinetic contrast sensitivity and light-adaptation,
      chicks are mice with wings.
AB  - BACKGROUND: Through adaptation, animals can function visually under an extremely
      broad range of light intensities. Light adaptation starts in the retina, through
      shifts in photoreceptor sensitivity and kinetics plus modulation of visual
      processing in retinal circuits. Although considerable research has been conducted
      on retinal adaptation in nocturnal species with rod-dominated retinas, such as
      the mouse, little is known about how cone-dominated avian retinas adapt to
      changes in mean light intensity. METHODOLOGY/PRINCIPAL FINDINGS: We used the
      optokinetic response to characterize contrast sensitivity (CS) in the chick
      retina as a function of spatial frequency and temporal frequency at different
      mean light intensities. We found that: 1) daytime, cone-driven CS was tuned to
      spatial frequency; 2) nighttime, presumably rod-driven CS was tuned to temporal
      frequency and spatial frequency; 3) daytime, presumably cone-driven CS at
      threshold intensity was invariant with temporal and spatial frequency; and 4)
      daytime photopic CS was invariant with clock time. CONCLUSION/SIGNIFICANCE: Light
      and dark-adaptational changes in CS were investigated comprehensively for the
      first time in the cone-dominated retina of an avian, diurnal species. The chick
      retina, like the mouse retina, adapts by using a "day/night" or "cone/rod" switch
      in tuning preference during changes in lighting conditions. The chick optokinetic
      response is an attractive model for noninvasive, behavioral studies of adaptation
      in retinal circuitry in health and disease.

PMID- 24098694
TI  - Decreased expression of nuclear p300 is associated with disease progression and
      worse prognosis of melanoma patients.
AB  - BACKGROUND: Genomic instability due to UV radiation is one of the leading causes
      for melanoma. Histone acetyltransferase p300 plays an indispensible role in DNA
      repair and maintenance of genomic integrity. The present study was performed to
      analyze the correlation between p300 expression, melanoma progression and patient
      survival. METHODS: Tissue microarray and immunohistochemical analysis was
      employed to study the expression of p300 in melanoma patients. A total of 358
      melanoma patients (250 primary melanoma and 108 metastatic melanoma) were used
      for the study. Kaplan-Meier, univariate and multivariate Cox regression analysis,
      and receiver-operating characteristic curves, were used to elucidate the
      prognostic significance of p300 expression. RESULTS: Our results demonstrate that
      p300 is expressed in both nucleus and cytoplasm but the nuclear expression of
      p300 is predominant. The progression of disease from dysplastic nevi to primary
      melanoma and to metastatic melanoma was associated with decreased nuclear and
      increased cytoplasmic p300 expression. Especially, the loss of nuclear and gain
      in cytoplasmic p300 was correlated with the progression of melanoma from AJCC
      stage II to stage III, which requires the migration and metastasis of cancer
      cells from primary sites to lymph nodes. Similarly, decrease in nuclear, and
      increase in cytoplasmic p300 expression correlated with worse survival of
      melanoma patients. Nuclear p300 but not cytoplasmic p300 could predict the
      patient survival independent of AJCC stage, age and gender. CONCLUSION: Loss of
      nuclear p300 expression is an indicator of worse patient survival and is an
      independent prognostic marker for melanoma.

PMID- 24098695
TI  - Characterization of the Kingella kingae polysaccharide capsule and
      exopolysaccharide.
AB  - Recent evidence indicates that Kingella kingae produces a polysaccharide capsule.
      In an effort to determine the composition and structure of this polysaccharide
      capsule, in the current study we purified capsular material from the surface of
      K. kingae strain 269-492 variant KK01 using acidic conditions to release the
      capsule and a series of steps to remove DNA, RNA, and protein. Analysis of the
      resulting material by gas chromatography and mass spectrometry revealed N-acetyl
      galactosamine (GalNAc), 3-deoxy-D-manno-oct-2-ulosonic acid (Kdo), and galactose
      (Gal). Further analysis by NMR demonstrated two distinct polysaccharides, one
      consisting of GalNAc and Kdo with the structure ->3)-beta-GalpNAc-(1->5)-beta
      Kdop-(2-> and the other containing galactose alone with the structure ->5)-beta
      Galf-(1->. Disruption of the ctrA gene required for surface localization of the
      K. kingae polysaccharide capsule resulted in elimination of GalNAc and Kdo but
      had no effect on the presence of Gal in bacterial surface extracts. In contrast,
      deletion of the pamABCDE locus involved in production of a reported galactan
      exopolysaccharide eliminated Gal but had no effect on the presence of GalNAc and
      Kdo in surface extracts. Disruption of ctrA and deletion of pamABCDE resulted in
      a loss of all carbohydrates in surface extracts. These results establish that K.
      kingae strain KK01 produces a polysaccharide capsule with the structure ->3)-beta
      GalpNAc-(1->5)-beta-Kdop-(2-> and a separate exopolysaccharide with the structure
      ->5)-beta-Galf-(1->. The polysaccharide capsule and the exopolysaccharide require
      distinct genetic loci for surface localization. 

PMID- 24098696
TI  - A purine analog synergizes with chloroquine (CQ) by targeting Plasmodium
      falciparum Hsp90 (PfHsp90).
AB  - BACKGROUND: Drug resistance, absence of an effective vaccine, and inadequate
      public health measures are major impediments to controlling Plasmodium falciparum
      malaria worldwide. The development of antimalarials to which resistance is less
      likely is paramount. To this end, we have exploited the chaperone function of P.
      falciparum Hsp90 (PfHsp90) that serves to facilitate the expression of resistance
      determinants. METHODS: The affinity and activity of a purine analogue Hsp90
      inhibitor (PU-H71) on PfHsp90 was determined using surface plasmon resonance
      (SPR) studies and an ATPase activity assay, respectively. In vitro, antimalarial
      activity was quantified using flow cytometry. Interactors of PfHsp90 were
      determined by LC-MS/MS. In vivo studies were conducted using the Plasmodium
      berghei infection mouse model. RESULTS: PU-H71 exhibited antimalarial activity in
      the nanomolar range, displayed synergistic activity with chloroquine in vitro.
      Affinity studies reveal that the PfHsp90 interacts either directly or indirectly
      with the P. falciparum chloroquine resistance transporter (PfCRT) responsible for
      chloroquine resistance. PU-H71 synergized with chloroquine in the P.berghei mouse
      model of malaria to reduce parasitemia and improve survival. CONCLUSIONS: We
      propose that the interaction of PfHsp90 with PfCRT may account for the observed
      antimalarial synergy and that PU-H71 is an effective adjunct for combination
      therapy.

PMID- 24098697
TI  - Monooxygenase, a novel beta-cypermethrin degrading enzyme from Streptomyces sp.
AB  - The widely used insecticide beta-cypermethrin has become a public concern because
      of its environmental contamination and toxic effects on mammals. In this study, a
      novel beta-cypermethrin degrading enzyme designated as CMO was purified to
      apparent homogeneity from a Streptomyces sp. isolate capable of utilizing beta
      cypermethrin as a growth substrate. The native enzyme showed a monomeric
      structure with a molecular mass of 41 kDa and pI of 5.4. The enzyme exhibited the
      maximal activity at pH 7.5 and 30 degrees C. It was fairly stable in the pH range
      from 6.5-8.5 and at temperatures below 10 degrees C. The enzyme activity was
      significantly stimulated by Fe(2+), but strongly inhibited by Ag(+), Al(3+), and
      Cu(2+). The enzyme catalyzed the degradation of beta-cypermethrin to form five
      products via hydroxylation and diaryl cleavage. A novel beta-cypermethrin
      detoxification pathway was proposed based on analysis of these products. The
      purified enzyme was identified as a monooxygenase by matrix-assisted laser
      desorption/ionization time-of-flight/time-of-flight mass spectrometry analysis
      (MALDI-TOF-MS) and N-terminal protein sequencing. Given that all the
      characterized pyrethroid-degrading enzymes are the members of hydrolase family,
      CMO represents the first pyrethroid-degrading monooxygenase identified from
      environmental microorganisms. Taken together, our findings depict a novel
      pyrethroid degradation mechanism and indicate that the purified enzyme may be a
      promising candidate for detoxification of beta-cypermethrin and environmental
      protection. 

PMID- 24098698
TI  - Genome aberrations in canine mammary carcinomas and their detection in cell-free
      plasma DNA.
AB  - Mammary tumors are the most frequent cancers in female dogs exhibiting a variety
      of histopathological differences. There is lack of knowledge about the genomes of
      these common dog tumors. Five tumors of three different histological subtypes
      were evaluated. Massive parallel sequencing (MPS) was performed in comparison to
      the respective somatic genome of each animal. Copy number and structural
      aberrations were validated using droplet digital PCR (ddPCR). Using mate-pair
      sequencing chromosomal aneuploidies were found in two tumors, frequent smaller
      deletions were found in one, inter-chromosomal fusions in one other, whereas one
      tumor was almost normal. These aberrations affect several known cancer associated
      genes such as cMYC, and KIT. One common deletion of the proximal end of CFA27,
      harboring the tumor suppressor gene PFDN5 was detected in four tumors. Using
      ddPCR, this deletion was validated and detected in 50% of tumors (N = 20).
      Breakpoint specific dPCRs were established for four tumors and tumor specific
      cell-free DNA (cfDNA) was detected in the plasma. In one animal tumor-specific
      cfDNA was found >1 year after surgery, attributable to a lung metastasis. Paired
      end sequencing proved that copy-number imbalances of the tumor are reflected by
      the cfDNA. This report on chromosomal instability of canine mammary cancers
      reveals similarities to human breast cancers as well as special canine
      alterations. This animal model provides a framework for using MPS for screening
      for individual cancer biomarkers with cost effective confirmation and monitoring
      using ddPCR. The possibility exists that ddPCR can be expanded to screening for
      common cancer related variants. 

PMID- 24098699
TI  - Performance of rapid diagnostic tests for imported malaria in clinical practice:
      results of a national multicenter study.
AB  - We compared the performance of four rapid diagnostic tests (RDTs) for imported
      malaria, and particularly Plasmodium falciparum infection, using thick and thin
      blood smears as the gold standard. All the tests are designed to detect at least
      one protein specific to P. falciparum (Plasmodium histidine-rich protein 2
      (PfHRP2) or Plasmodium LDH (PfLDH)) and one pan-Plasmodium protein (aldolase or
      Plasmodium LDH (pLDH)). 1,311 consecutive patients presenting to 9 French
      hospitals with suspected malaria were included in this prospective study between
      April 2006 and September 2008. Blood smears revealed malaria parasites in 374
      cases (29%). For the diagnosis of P. falciparum infection, the three tests
      detecting PfHRP2 showed high and similar sensitivity (96%), positive predictive
      value (PPV) (90%) and negative predictive value (NPV) (98%). The PfLDH test
      showed lower sensitivity (83%) and NPV (80%), despite good PPV (98%). For the
      diagnosis of non-falciparum species, the PPV and NPV of tests targeting pLDH or
      aldolase were 94-99% and 52-64%, respectively. PfHRP2-based RDTs are thus an
      acceptable alternative to routine microscopy for diagnosing P. falciparum
      malaria. However, as malaria may be misdiagnosed with RDTs, all negative results
      must be confirmed by the reference diagnostic method when clinical, biological or
      other factors are highly suggestive of malaria. 

PMID- 24098700
TI  - Distribution of mosquitoes in the south east of Argentina and first report on the
      analysis based on 18S rDNA and COI sequences.
AB  - Although Mar del Plata is the most important city on the Atlantic coast of
      Argentina, mosquitoes inhabiting such area are almost uncharacterized. To
      increase our knowledge in their distribution, we sampled specimens of natural
      populations. After the morphological identification based on taxonomic keys,
      sequences of DNA from small ribosomal subunit (18S rDNA) and cytochrome c oxidase
      I (COI) genes were obtained from native species and the phylogenetic analysis of
      these sequences were done. Fourteen species from the genera Uranotaenia, Culex,
      Ochlerotatus and Psorophora were found and identified. Our 18S rDNA and COI-based
      analysis indicates the relationships among groups at the supra-species level in
      concordance with mosquito taxonomy. The introduction and spread of vectors and
      diseases carried by them are not known in Mar del Plata, but some of the species
      found in this study were reported as pathogen vectors. 

PMID- 24098701
TI  - Targeting p35/Cdk5 signalling via CIP-peptide promotes angiogenesis in hypoxia.
AB  - Cyclin-dependent kinase-5 (Cdk5) is over-expressed in both neurons and
      microvessels in hypoxic regions of stroke tissue and has a significant
      pathological role following hyper-phosphorylation leading to calpain-induced cell
      death. Here, we have identified a critical role of Cdk5 in cytoskeleton/focal
      dynamics, wherein its activator, p35, redistributes along actin microfilaments of
      spreading cells co-localising with p(Tyr15)Cdk5, talin/integrin beta-1 at the
      lamellipodia in polarising cells. Cdk5 inhibition (roscovitine) resulted in actin
      cytoskeleton disorganisation, prevention of protein co-localization and
      inhibition of movement. Cells expressing Cdk5 (D144N) kinase mutant, were unable
      to spread, migrate and form tube-like structures or sprouts, while Cdk5 wild-type
      over-expression showed enhanced motility and angiogenesis in vitro, which was
      maintained during hypoxia. Gene microarray studies demonstrated myocyte enhancer
      factor (MEF2C) as a substrate for Cdk5-mediated angiogenesis in vitro. MEF2C
      showed nuclear co-immunoprecipitation with Cdk5 and almost complete inhibition of
      differentiation and sprout formation following siRNA knock-down. In hypoxia,
      insertion of Cdk5/p25-inhibitory peptide (CIP) vector preserved and enhanced in
      vitro angiogenesis. These results demonstrate the existence of critical and
      complementary signalling pathways through Cdk5 and p35, and through which
      coordination is a required factor for successful angiogenesis in sustained
      hypoxic condition. 

PMID- 24098702
TI  - Live attenuated Rev-independent Nef-SIV enhances acquisition of heterologous
      SIVsmE660 in acutely vaccinated rhesus macaques.
AB  - BACKGROUND: Rhesus macaques (RMs) inoculated with live-attenuated Rev-Independent
      Nef- simian immunodeficiency virus (Rev-Ind Nef-SIV) as adults or neonates
      controlled viremia to undetectable levels and showed no signs of immunodeficiency
      over 6-8 years of follow-up. We tested the capacity of this live-attenuated virus
      to protect RMs against pathogenic, heterologous SIVsmE660 challenges.
      METHODOLOGY/PRINCIPAL FINDINGS: Three groups of four RM were inoculated with Rev
      Ind Nef-SIV and compared. Group 1 was inoculated 8 years prior and again 15
      months before low dose intrarectal challenges with SIVsmE660. Group 2 animals
      were inoculated with Rev-Ind Nef-SIV at 15 months and Group 3 at 2 weeks prior to
      the SIVsmE660 challenges, respectively. Group 4 served as unvaccinated controls.
      All RMs underwent repeated weekly low-dose intrarectal challenges with SIVsmE660.
      Surprisingly, all RMs with acute live-attenuated virus infection (Group 3) became
      superinfected with the challenge virus, in contrast to the two other vaccine
      groups (Groups 1 and 2) (P=0.006 for each) and controls (Group 4) (P=0.022). Gene
      expression analysis showed significant upregulation of innate immune response
      related chemokines and their receptors, most notably CCR5 in Group 3 animals
      during acute infection with Rev-Ind Nef-SIV. CONCLUSIONS/SIGNIFICANCE: We
      conclude that although Rev-Ind Nef-SIV remained apathogenic, acute replication of
      the vaccine strain was not protective but associated with increased acquisition
      of heterologous mucosal SIVsmE660 challenges.

PMID- 24098703
TI  - Relaxin protects rat lungs from ischemia-reperfusion injury via inducible NO
      synthase: role of ERK-1/2, PI3K, and forkhead transcription factor FKHRL1.
AB  - INTRODUCTION: Early allograft dysfunction following lung transplantation is
      mainly an ischemia/reperfusion (IR) injury. We showed that relaxin-2 (relaxin)
      exerts a protective effect in lung IR, attributable to decreases in endothelin-1
      (ET-1) production, leukocyte recruitment, and free radical generation. Here, we
      summarize our investigations into relaxin's signalling. MATERIALS AND METHODS:
      Isolated rat lungs were perfused with vehicle or 5 nM relaxin (n = 6-10 each).
      Thereafter, experiments were conducted in the presence of relaxin plus vehicle,
      the protein kinase A inhibitors H-89 and KT-5720, the NO synthase (NOS) inhibitor
      L-NAME, the iNOS inhibitor 1400W, the nNOS inhibitor SMTC, the extracellular
      signal-regulated kinase-1/2 (ERK-1/2) inhibitor PD-98059, the
      phosphatidylinositol-3 kinase (PI3K) inhibitor wortmannin, the endothelin type-B
      (ETB) antagonist A-192621, or the glucocorticoid receptor (GR) antagonist RU-486.
      After 90 min ischemia and 90 min reperfusion we determined wet-to-dry (W/D)
      weight ratio, mean pulmonary arterial pressure (MPAP), vascular release of ET-1,
      neutrophil elastase (NE), myeloperoxidase (MPO), and malondialdehyde (MDA).
      Primary rat pulmonary vascular cells were similarly treated. RESULTS: IR lungs
      displayed significantly elevated W/D ratios, MPAP, as well as ET-1, NE, MDA, and
      MPO. In the presence of relaxin, all of these parameters were markedly improved.
      This protective effect was completely abolished by L-NAME, 1400W, PD-98059, and
      wortmannin whereas neither PKA and nNOS inhibition nor ETB and GR antagonism were
      effective. Analysis of NOS gene expression and activity revealed that the relaxin
      induced early and moderate iNOS stimulation is ERK-1/2-dependent and counter
      balanced by PI3K. Relaxin-PI3K-related phosphorylation of a forkhead
      transcription factor, FKHRL1, paralleled this regulation. In pulmonary
      endothelial and smooth muscle cells, FKHRL1 was essential to relaxin-PI3K
      signalling towards iNOS. CONCLUSION: In this short-time experimental setting,
      relaxin protects against IR-induced lung injury via early and moderate iNOS
      induction, dependent on balanced ERK-1/2 and PI3K-FKHRL1 stimulation. These
      findings render relaxin a candidate drug for lung preservation.

PMID- 24098704
TI  - Changes in the abundance of grassland species in monocultures versus mixtures and
      their relation to biodiversity effects.
AB  - Numerous studies have reported positive effects of species richness on plant
      community productivity. Such biodiversity effects are usually quantified by
      comparing the performance of plant mixtures with reference monocultures. However,
      several mechanisms, such as the lack of resource complementarity and facilitation
      or the accumulation of detrimental agents, suggest that monocultures are more
      likely than mixtures to deteriorate over time. Increasing biodiversity effects
      over time could therefore result from declining monocultures instead of
      reflecting increases in the functioning of mixtures. Commonly, the latter is
      assumed when positive trends in biodiversity effects occur. Here, we analysed the
      performance of 60 grassland species growing in monocultures and mixtures over 9
      years in a biodiversity experiment to clarify whether their temporal biomass
      dynamics differed and whether a potential decline of monocultures contributed
      significantly to the positive net biodiversity effect observed. Surprisingly,
      individual species' populations produced, on average, significantly more biomass
      per unit area when growing in monoculture than when growing in mixture. Over
      time, productivity of species decreased at a rate that was, on average, slightly
      more negative in monocultures than in mixtures. The mean net biodiversity effect
      across all mixtures was continuously positive and ranged between 64-217 g per
      m(2). Short-term increases in the mean net biodiversity effect were only partly
      due to deteriorating monocultures and were strongly affected by particular
      species gaining dominance in mixtures in the respective years. We conclude that
      our species performed, on average, comparably in monocultures and mixtures;
      monoculture populations being slightly more productive than mixture populations
      but this trend decreased over time. This suggested that negative feedbacks had
      not yet affected monocultures strongly but could potentially become more evident
      in the future. Positive biodiversity effects on aboveground productivity were
      heavily driven by a small, but changing, set of species that behaved differently
      from the average species. 

PMID- 24098705
TI  - Field evaluation of a prototype paper-based point-of-care fingerstick
      transaminase test.
AB  - Monitoring for drug-induced liver injury (DILI) via serial transaminase
      measurements in patients on potentially hepatotoxic medications (e.g., for HIV
      and tuberculosis) is routine in resource-rich nations, but often unavailable in
      resource-limited settings. Towards enabling universal access to affordable point
      of-care (POC) screening for DILI, we have performed the first field evaluation of
      a paper-based, microfluidic fingerstick test for rapid, semi-quantitative, visual
      measurement of blood alanine aminotransferase (ALT). Our objectives were to
      assess operational feasibility, inter-operator variability, lot variability,
      device failure rate, and accuracy, to inform device modification for further
      field testing. The paper-based ALT test was performed at POC on fingerstick
      samples from 600 outpatients receiving HIV treatment in Vietnam. Results, read
      independently by two clinic nurses, were compared with gold-standard automated
      (Roche Cobas) results from venipuncture samples obtained in parallel. Two device
      lots were used sequentially. We demonstrated high inter-operator agreement, with
      96.3% (95% C.I., 94.3-97.7%) agreement in placing visual results into clinically
      defined "bins" (<3x, 3-5x, and >5x upper limit of normal), >90% agreement in
      validity determination, and intraclass correlation coefficient of 0.89 (95% C.I.,
      0.87-0.91). Lot variability was observed in % invalids due to hemolysis (21.1%
      for Lot 1, 1.6% for Lot 2) and correlated with lots of incorporated plasma
      separation membranes. Invalid rates <1% were observed for all other device
      controls. Overall bin placement accuracy for the two readers was 84%
      (84.3%/83.6%). Our findings of extremely high inter-operator agreement for visual
      reading-obtained in a target clinical environment, as performed by local
      practitioners-indicate that the device operation and reading process is feasible
      and reproducible. Bin placement accuracy and lot-to-lot variability data
      identified specific targets for device optimization and material quality control.
      This is the first field study performed with a patterned paper-based microfluidic
      device and opens the door to development of similar assays for other important
      analytes. 

PMID- 24098707
TI  - Individual-based simulation models of HIV transmission: reporting quality and
      recommendations.
AB  - BACKGROUND: Individual-based modeling is a growing technique in the HIV
      transmission and prevention literature, but insufficient attention has been paid
      to formally evaluate the quality of reporting in this field. We present reporting
      recommendations for individual-based models for HIV treatment and prevention,
      assess the quality of reporting in the existing literature, and comment on the
      contribution of this model type to HIV policy and prediction. METHODS: We
      developed reporting recommendations for individual-based HIV transmission
      mathematical models, and through a systematic search, used them to evaluate the
      reporting in the existing literature. We identified papers that employed
      individual-based simulation models and were published in English prior to
      December 31, 2012. Articles were included if the models they employed simulated
      and tracked individuals, simulated HIV transmission between individuals in a
      particular population, and considered a particular treatment or prevention
      intervention. The papers were assessed with the reporting recommendations.
      FINDINGS: Of 214 full text articles examined, 32 were included in the evaluation,
      representing 20 independent individual-based HIV treatment and prevention
      mathematical models. Manuscripts universally reported the objectives, context,
      and modeling conclusions in the context of the modeling assumptions and the
      model's predictive capabilities, but the reporting of individual-based modeling
      methods, parameterization and calibration was variable. Six papers discussed the
      time step used and one discussed efforts to maintain internal validity in coding.
      CONCLUSION: Individual-based models represent detailed HIV transmission processes
      with the potential to contribute to inference and policy making for many
      different regions and populations. The rigor in reporting of assumptions,
      methods, and calibration of individual-based models focused on HIV transmission
      and prevention varies greatly. Higher standards for reporting of statistically
      rigorous calibration and model assumption testing need to be implemented to
      increase confidence in existing and future modeling results.

PMID- 24098706
TI  - Keratocyte apoptosis and not myofibroblast differentiation mark the graft/host
      interface at early time-points post-DSAEK in a cat model.
AB  - PURPOSE: To evaluate myofibroblast differentiation as an etiology of haze at the
      graft-host interface in a cat model of Descemet's Stripping Automated Endothelial
      Keratoplasty (DSAEK). METHODS: DSAEK was performed on 10 eyes of 5 adult domestic
      short-hair cats. In vivo corneal imaging with slit lamp, confocal, and optical
      coherence tomography (OCT) were performed twice weekly. Cats were sacrificed and
      corneas harvested 4 hours, and 2, 4, 6, and 9 days post-DSAEK. Corneal sections
      were stained with the TUNEL method and immunohistochemistry was performed for
      alpha-smooth muscle actin (alpha-SMA) and fibronectin with DAPI counterstain.
      RESULTS: At all in vivo imaging time-points, corneal OCT revealed an increase in
      backscatter of light and confocal imaging revealed an acellular zone at the graft
      host interface. At all post-mortem time-points, immunohistochemistry revealed a
      complete absence of alpha-SMA staining at the graft-host interface. At 4 hours,
      extracellular fibronectin staining was identified along the graft-host interface
      and both fibronectin and TUNEL assay were positive within adjacent cells
      extending into the host stroma. By day 2, fibronectin and TUNEL staining
      diminished and a distinct acellular zone was present in the region of previously
      TUNEL-positive cells. CONCLUSIONS: OCT imaging consistently showed increased
      reflectivity at the graft-host interface in cat corneas in the days post-DSAEK.
      This was not associated with myofibroblast differentiation at the graft-host
      interface, but rather with apoptosis and the development of a subsequent
      acellular zone. The roles of extracellular matrix changes and keratocyte cell
      death and repopulation should be investigated further as potential contributors
      to the interface optical changes.

PMID- 24098708
TI  - MicroRNA-21-3p, a berberine-induced miRNA, directly down-regulates human
      methionine adenosyltransferases 2A and 2B and inhibits hepatoma cell growth.
AB  - Methionine adenosyltransferase (MAT) is the cellular enzyme that catalyzes the
      synthesis of S-adenosylmethionine (SAM), the principal biological methyl donor
      and a key regulator of hepatocyte proliferation, death and differentiation. Two
      genes, MAT1A and MAT2A, encode 2 distinct catalytic MAT isoforms. A third gene,
      MAT2B, encodes a MAT2A regulatory subunit. In hepatocellular carcinoma (HCC),
      MAT1A downregulation and MAT2A upregulation occur, known as the MAT1A:MAT2A
      switch. The switch is accompanied with an increasing expression of MAT2B, which
      results in decreased SAM levels and facilitates cancer cell growth. Berberine, an
      isoquinoline alkaloid isolated from many medicinal herbs such as Coptis
      chinensis, has a wide range of pharmacological effects including anti-cancer
      effects. Because drug-induced microRNAs have recently emerged as key regulators
      in guiding their pharmacological effects, we examined whether microRNA expression
      is differentially altered by berberine treatment in HCC. In this study, we used
      microRNA microarrays to find that the expression level of miR-21-3p (previously
      named miR-21*) increased after berberine treatment in the HepG2 human hepatoma
      cell line. To predict the putative targets of miR-21-3p, we integrated the gene
      expression profiles of HepG2 cells after berberine treatment by comparing with a
      gene list generated from sequence-based microRNA target prediction software. We
      then confirmed these predictions through transfection of microRNA mimics and a 3'
      UTR reporter assay. Our findings provide the first evidence that miR-21-3p
      directly reduces the expression of MAT2A and MAT2B by targeting their 3' UTRs. In
      addition, an overexpression of miR-21-3p increased intracellular SAM contents,
      which have been proven to be a growth disadvantage for hepatoma cells. The
      overexpression of miR-21-3p suppresses growth and induces apoptosis in HepG2
      cells. Overall, our results demonstrate that miR-21-3p functions as a tumor
      suppressor by directly targeting both MAT2A and MAT2B, indicating its therapeutic
      potential in HCC. 

PMID- 24098709
TI  - Soup consumption is associated with a reduced risk of overweight and obesity but
      not metabolic syndrome in US adults: NHANES 2003-2006.
AB  - A limited number of studies have found that soup consumption is related to a
      lower risk of overweight and obesity in Asian and European populations, however,
      these studies do not provide a consistent picture regarding the association
      between soup consumption and markers of metabolic syndrome. To date, no study
      examining the relationship between soup and body weight or metabolic syndrome
      have been conducted in the US population. The present study used a sample of 4158
      adults aged 19-64 who participated in the National Health and Nutrition
      Examination Survey between 2003 and 2006. The frequency of soup consumption was
      determined using a food frequency questionnaire. The weighted prevalence of soup
      consumption was 94%, with a seasonal variation in the frequency of soup
      consumption being found. Non-consumers of soup were at a higher risk of being
      overweight or obese (adjusted odds ratio = 1.381, P = 0.013), with a higher
      adjusted prevalence of reduced HDL cholesterol (adjusted odds ratio = 1.280, P =
      0.045), but there was no association between soup consumption and metabolic
      syndrome (P = 0.520). The frequency of soup consumption was inversely associated
      with covariate-adjusted body mass index and waist circumference (P<0.05), but not
      with biomarkers of metabolic syndrome, except for a lower fasting insulin level
      in frequent soup consumers (P = 0.022). Results from the present study suggest
      soup consumption is not associated with metabolic syndrome. However, there is an
      inverse relationship between soup consumption and body weight status in US
      adults, which support laboratory studies showing a potential benefit of soup
      consumption for body weight management. 

PMID- 24098710
TI  - Perceived parent-adolescent relationship, perceived parental online behaviors and
      pathological internet use among adolescents: gender-specific differences.
AB  - This study examined the associations between adolescents' perceived relationships
      with their parents, perceived parental online behaviors, and Pathological
      Internet Use (PIU) among adolescents. Additional testing was carried out to
      determine the effect of different genders (parent and adolescent). Cross
      sectional data was collected from 4,559 students aged 12 to 21 years in the
      cities of Beijing and Jinan, People's Republic of China. Participants responded
      to an anonymous questionnaire concerning their Internet use behavior, perceived
      parental Internet use behaviors, and perceived parent-adolescent relationship.
      Hierarchical linear regressions controlling for adolescents' age were conducted.
      Results showed different effects of parent and adolescent gender on perceived
      parent-adolescent relationship and parent Internet use behavior, as well as some
      other gender-specific associations. Perceived father-adolescent relationship was
      the most protective factor against adolescent PIU with perceived maternal
      Internet use positively predicting PIU for both male and female adolescents.
      However, perceived paternal Internet use behaviors positively predicted only
      female adolescent PIU. Results indicated a different effect pathway for fathers
      and mothers on boys and girls, leading to discussion of the implications for
      prevention and intervention. 

PMID- 24098711
TI  - Impaired functions of macrophage from cystic fibrosis patients: CD11b, TLR-5
      decrease and sCD14, inflammatory cytokines increase.
AB  - BACKGROUND: Early in life, cystic fibrosis (CF) patients are infected with
      microorganisms. The role of macrophages has largely been underestimated in
      literature, whereas the focus being mostly on neutrophils and epithelial cells.
      Macrophages may however play a significant role in the initiating stages of this
      disease, via an inability to act as a suppressor cell. Yet macrophage dysfunction
      may be the first step in cascade of events leading to chronic
      inflammation/infection in CF. Moreover, reports have suggested that CFTR
      contribute to altered inflammatory response in CF by modification of normal
      macrophage functions. OBJECTIVES: In order to highlight possible intrinsic
      macrophage defects due to impaired CFTR, we have studied inflammatory cytokines
      secretions, recognition of pathogens and phagocytosis in peripheral blood
      monocyte-derived macrophages from stable adult CF patients and healthy subjects
      (non-CF). RESULTS: In CF macrophage supernatants, concentrations of sCD14, IL
      1beta, IL-6, TNF-alpha and IL-10 were strongly raised. Furthermore expression of
      CD11b and TLR-5 were sorely decreased on CF macrophages. Beside, no difference
      was observed for mCD14, CD16, CD64, TLR-4 and TLR1/TLR-2 expressions. Moreover, a
      strong inhibition of phagocytosis was observed for CF macrophages. Elsewhere CFTR
      inhibition in non-CF macrophages also led to alterations of phagocytosis function
      as well as CD11b expression. CONCLUSIONS: Altogether, these findings demonstrate
      excessive inflammation in CF macrophages, characterized by overproduction of
      sCD14 and inflammatory cytokines, with decreased expression of CD11b and TLR-5,
      and impaired phagocytosis. This leads to altered clearance of pathogens and non
      resolution of infection by CF macrophages, thereby inducing an exaggerated pro
      inflammatory response.

PMID- 24098712
TI  - Arginine methylation of hnRNP A2 does not directly govern its subcellular
      localization.
AB  - The hnRNP A/B paralogs A1, A2/B1 and A3 are key components of the nuclear 40S
      hnRNP core particles. Despite a high degree of sequence similarity, increasing
      evidence suggests they perform additional, functionally distinct roles in RNA
      metabolism. Here we identify and study the functional consequences of
      differential post-translational modification of hnRNPs A1, A2 and A3. We show
      that while arginine residues in the RGG box domain of hnRNP A1 and A3 are almost
      exhaustively, asymmetrically dimethylated, hnRNP A2 is dimethylated at only a
      single residue (Arg-254) and this modification is conserved across cell types. It
      has been suggested that arginine methylation regulates the nucleocytoplasmic
      distribution of hnRNP A/B proteins. However, we show that transfected cells
      expressing an A2(R254A) point mutant exhibit no difference in subcellular
      localization. Similarly, immunostaining and mass spectrometry of endogenous hnRNP
      A2 in transformed cells reveals a naturally-occurring pool of unmethylated
      protein but an exclusively nuclear pattern of localization. Our results suggest
      an alternative role for post-translational arginine methylation of hnRNPs and
      offer further evidence that the hnRNP A/B paralogs are not functionally
      redundant. 

PMID- 24098713
TI  - Blockade of the formation of insoluble ubiquitinated protein aggregates by
      EGCG3"Me in the alloxan-induced diabetic kidney.
AB  - BACKGROUND: Renal accumulation of reactive carbonyl compounds (RCCs) has been
      linked to the progression of diabetic nephropathy. We previously demonstrated
      that carbonyl stress induces the formation of amino-carbonyl cross-links and
      sharply increases the content of beta-sheet-rich structures, which is the seed of
      insoluble aggregates formation, and tea catechin (-)-epigallocatechin 3-gallate
      (EGCG) can reverse this process in vitro and in vivo. In this study, methylated
      derivative (-)-epigallocatechin-3-O-(3-O-methyl)-gallate (EGCG3"Me) was
      hypothesized to neutralize carbonyl stress mediating the formation of insoluble
      ubiquitinated protein (IUP) aggregates, and reduce the early development of
      diabetic nephropathy. METHODS AND RESULTS: Diabetes was induced in mice by
      intraperitoneally injecting alloxan monohydrate (200 mg/kg/d) twice and
      administering EGCG3"Me by gavage for 15 d. Reagent case and western blot results
      showed that, in diabetic kidneys, the carbonyl proteins in the serum increased;
      and in insoluble protein fraction, 4-hydroxynonenal-modified proteins, IUP
      aggregates and p62 accumulated; FT-IR study demonstrated that the lipid content,
      anti-parallel beta-sheet structure and aggregates increased. EGCG3"Me treatment
      could effectively reverse this process, even better than the negative control
      treatment. CONCLUSIONS: EGCG3"Me exhibiting anti-beta-sheet-rich IUP aggregate
      properties, maybe represents a new strategy to impede the progression of diabetic
      nephropathy and other diabetic complications.

PMID- 24098714
TI  - Avian cytochrome P450 (CYP) 1-3 family genes: isoforms, evolutionary
      relationships, and mRNA expression in chicken liver.
AB  - Cytochrome P450 (CYP) of chicken and other avian species have been studied
      primarily with microsomes or characterized by cloning and protein expression.
      However, the overall existing isoforms in avian CYP1-3 families or dominant
      isoforms in avian xenobiotic metabolism have not yet been elucidated. In this
      study, we aimed to clarify and classify all of the existing isoforms of CYP1-3 in
      avian species using available genome assemblies for chicken, zebra finch, and
      turkey. Furthermore, we performed qRT-PCR assay to identify dominant CYP genes in
      chicken liver. Our results suggested that avian xenobiotic-metabolizing CYP genes
      have undergone unique evolution such as CYP2C and CYP3A genes, which have
      undergone avian-specific gene duplications. qRT-PCR experiments showed that
      CYP2C45 was the most highly expressed isoform in chicken liver, while CYP2C23b
      was the most highly induced gene by phenobarbital. Considering together with the
      result of further enzymatic characterization, CYP2C45 may have a dominant role in
      chicken xenobiotic metabolism due to the constitutive high expression levels,
      while CYP2C23a and CYP2C23b can be greatly induced by chicken xenobiotic receptor
      (CXR) activators. These findings will provide not only novel insights into avian
      xenobiotic metabolism, but also a basis for the further characterization of each
      CYP gene. 

PMID- 24098715
TI  - A pathogenic nematode targets recognition proteins to avoid insect defenses.
AB  - Steinernemacarpocapsae is a nematode pathogenic in a wide variety of insect
      species. The great pathogenicity of this nematode has been ascribed to its
      ability to overcome the host immune response; however, little is known about the
      mechanisms involved in this process. The analysis of an expressed sequence tags
      (EST) library in the nematode during the infective phase was performed and a
      highly abundant contig homologous to serine protease inhibitors was identified.
      In this work, we show that this contig is part of a 641-bp cDNA that encodes a
      BPTI-Kunitz family inhibitor (Sc-KU-4), which is up-regulated in the parasite
      during invasion and installation. Recombinant Sc-KU-4 protein was produced in
      Escherichia coli and shown to inhibit chymotrypsin and elastase activities in a
      dose-dependent manner by a competitive mechanism with Ki values of 1.8 nM and 2.6
      nM, respectively. Sc-KU-4 also inhibited trypsin and thrombin activities to a
      lesser extent. Studies of the mode of action of Sc-KU-4 and its effects on insect
      defenses suggest that although Sc-KU-4 did not inhibit the activation of
      hemocytes or the formation of clotting fibers, it did inhibit hemocyte
      aggregation and the entrapment of foreign particles by fibers. Moreover, Sc-KU-4
      avoided encapsulation and the deposition of clotting materials, which usually
      occurs in response to foreign particles. We show by protein-protein interaction
      that Sc-KU-4 targets recognition proteins of insect immune system such as
      masquerade-like and serine protease-like homologs. The interaction of Sc-KU-4
      with these proteins explains the ability of the nematode to overcome host
      reactions and its large pathogenic spectrum, once these immune proteins are well
      conserved in insects. The discovery of this inhibitor targeting insect
      recognition proteins opens new avenues for the development of S. carpocapsae as a
      biological control agent and provides a new tool to study host-pathogen
      interactions. 

PMID- 24098716
TI  - Small nerve fiber pathology in critical illness.
AB  - BACKGROUND: Degeneration of intraepidermal nerve fibers (IENF) is a hallmark of
      small fiber neuropathy of different etiology, whose clinical picture is dominated
      by neuropathic pain. It is unknown if critical illness can affect IENF. METHODS:
      We enrolled 14 adult neurocritical care patients with prolonged intensive care
      unit (ICU) stay and artificial ventilation (>= 3 days), and no previous history
      or risk factors for neuromuscular disease. All patients underwent neurological
      examination including evaluation of consciousness, sensory functions, muscle
      strength, nerve conduction study and needle electromyography, autonomic
      dysfunction using the finger wrinkling test, and skin biopsy for quantification
      of IENF and sweat gland innervation density during ICU stay and at follow-up
      visit. Development of infection, sepsis and multiple organ failure was recorded
      throughout the ICU stay. RESULTS: Of the 14 patients recruited, 13 (93%) had
      infections, sepsis or multiple organ failure. All had severe and non-length
      dependent loss of IENF. Sweat gland innervation was reduced in all except one
      patient. Of the 7 patients available for follow-up visit, three complained of
      diffuse sensory loss and burning pain, and another three showed clinical
      dysautonomia. CONCLUSIONS: Small fiber pathology can develop in the acute phase
      of critical illness and may explain chronic sensory impairment and pain in
      neurocritical care survivors. Its impact on long term disability warrants further
      studies involving also non-neurologic critical care patients.

PMID- 24098717
TI  - Human NK cell subset functions are differentially affected by adipokines.
AB  - BACKGROUND: Obesity is a risk factor for various types of infectious diseases and
      cancer. The increase in adipose tissue causes alterations in both adipogenesis
      and the production of adipocyte-secreted proteins (adipokines). Since natural
      killer (NK) cells are the host's primary defense against virus-infected and tumor
      cells, we investigated how adipocyte-conditioned medium (ACM) affects functions
      of two distinct human NK cell subsets. METHODS: Isolated human peripheral blood
      mononuclear cells (PBMCs) were cultured with various concentrations of human and
      murine ACM harvested on two different days during adipogenesis and analyzed by
      fluorescent-activated cell sorting (FACS). RESULTS: FACS analyses showed that the
      expression of tumor necrosis factor-related apoptosis-inducing ligand (TRAIL),
      granzyme A (GzmA) and interferon (IFN)-gamma in NK cells was regulated in a
      subset-specific manner. ACM treatment altered IFN-gamma expression in CD56(dim)
      NK cells. The production of GzmA in CD56(bright) NK cells was differentially
      affected by the distinct adipokine compositions harvested at different states of
      adipogenesis. Comparison of the treatment with either human or murine ACM
      revealed that adipokine-induced effects on NK cell expression of the leptin
      receptor (Ob-R), TRAIL and IFN-gamma were species-specific. CONCLUSION:
      Considering the growing prevalence of obesity and the various disorders related
      to it, the present study provides further insights into the roles human NK cell
      subsets play in the obesity-associated state of chronic low-grade inflammation.

PMID- 24098718
TI  - Differential distribution of major brain gangliosides in the adult mouse central
      nervous system.
AB  - Gangliosides - sialic acid-bearing glycolipids - are major cell surface
      determinants on neurons and axons. The same four closely related structures, GM1,
      GD1a, GD1b and GT1b, comprise the majority of total brain gangliosides in mammals
      and birds. Gangliosides regulate the activities of proteins in the membranes in
      which they reside, and also act as cell-cell recognition receptors. Understanding
      the functions of major brain gangliosides requires knowledge of their tissue
      distribution, which has been accomplished in the past using biochemical and
      immunohistochemical methods. Armed with new knowledge about the stability and
      accessibility of gangliosides in tissues and new IgG-class specific monoclonal
      antibodies, we investigated the detailed tissue distribution of gangliosides in
      the adult mouse brain. Gangliosides GD1b and GT1b are widely expressed in gray
      and white matter. In contrast, GM1 is predominately found in white matter and
      GD1a is specifically expressed in certain brain nuclei/tracts. These findings are
      considered in relationship to the hypothesis that gangliosides GD1a and GT1b act
      as receptors for an important axon-myelin recognition protein, myelin-associated
      glycoprotein (MAG). Mediating axon-myelin interactions is but one potential
      function of the major brain gangliosides, and more detailed knowledge of their
      distribution may help direct future functional studies. 

PMID- 24098719
TI  - Proteomic-based insight into Malpighian tubules of silkworm Bombyx mori.
AB  - Malpighian tubules (MTs) are highly specific organs of arthropods (Insecta,
      Myriapoda and Arachnida) for excretion and osmoregulation. In order to highlight
      the important genes and pathways involved in multi-functions of MTs, we performed
      a systematic proteomic analysis of silkworm MTs in the present work. Totally,
      1,367 proteins were identified by one-dimensional gel electrophoresis coupled
      with liquid chromatography-tandem mass spectrometry, and as well as by Trans
      Proteomic Pipeline (TPP) and Absolute protein expression (APEX) analyses. Forty
      one proteins were further identified by two-dimensional gel electrophoresis. Some
      proteins were revealed to be significantly associated with various metabolic
      processes, organic solute transport, detoxification and innate immunity. Our
      results might lay a good foundation for future functional studies of MTs in
      silkworm and other lepidoptera. 

PMID- 24098720
TI  - Tumor necrosis factor induces tumor promoting and anti-tumoral effects on
      pancreatic cancer via TNFR1.
AB  - Multiple activities are ascribed to the cytokine tumor necrosis factor (TNF) in
      health and disease. In particular, TNF was shown to affect carcinogenesis in
      multiple ways. This cytokine acts via the activation of two cell surface
      receptors, TNFR1, which is associated with inflammation, and TNFR2, which was
      shown to cause anti-inflammatory signaling. We assessed the effects of TNF and
      its two receptors on the progression of pancreatic cancer by in vivo
      bioluminescence imaging in a syngeneic orthotopic tumor mouse model with Panc02
      cells. Mice deficient for TNFR1 were unable to spontaneously reject Panc02 tumors
      and furthermore displayed enhanced tumor progression. In contrast, a fraction of
      wild type (37.5%), TNF deficient (12.5%), and TNFR2 deficient mice (22.2%) were
      able to fully reject the tumor within two weeks. Pancreatic tumors in TNFR1
      deficient mice displayed increased vascular density, enhanced infiltration of
      CD4(+) T cells and CD4(+) forkhead box P3 (FoxP3)(+) regulatory T cells (Treg)
      but reduced numbers of CD8(+) T cells. These alterations were further accompanied
      by transcriptional upregulation of IL4. Thus, TNF and TNFR1 are required in
      pancreatic ductal carcinoma to ensure optimal CD8(+) T cell-mediated
      immunosurveillance and tumor rejection. Exogenous systemic administration of
      human TNF, however, which only interacts with murine TNFR1, accelerated tumor
      progression. This suggests that TNFR1 has basically the capability in the Panc02
      model to trigger pro-and anti-tumoral effects but the spatiotemporal availability
      of TNF seems to determine finally the overall outcome. 

PMID- 24098721
TI  - An increase in vascular endothelial growth factor (VEGF) and VEGF soluble
      receptor-1 (sFlt-1) are associated with early recurrent spontaneous abortion.
AB  - Recurrent spontaneous abortion (RSA) is a health problem that affects
      approximately 1% to 5% reproductive age woman. Yet, in around half of these
      patients, the mechanism for RSA is unexplained. Recent studies have indicated
      that placental ischemia/hypoxia and endothelial dysfunction are important factors
      in miscarriage. Other studies have indicated that the level and expression of
      soluble FMS-like tyrosine kinase-1 (sFlt1) is increased under a hypoxic
      environment. However, decreased sFlt-1 in the maternal circulation during the
      first trimester has recently been proposed as a potential marker for identifying
      risk of pregnancy loss. In this prospective study clinical samples were obtained
      within a short time after the fetal death, protein expression and maternal serum
      levels of sFlt1 were assessed and compared to samples taken from those with
      normal pregnancies. Our results indicate that levels of VEGF and sFlt-1 are both
      increased in women during early pregnancy compared women that are not pregnant
      (p<0.05) indicating that VEGF and sFlt-1 are both associated with pregnancy. More
      importantly, we detected a significant (p<0.05) increase in sFlt1 and VEGF levels
      and expression in the RSA patients who suffered subsequent miscarriages compare
      to controls. These results demonstrate that there is likely a relationship
      between VEGF, sFlt-1 and RSA suggesting that the high levels and over expression
      of sFlt-1 and VEGF might be associated with the pathogenesis of RSA. 

PMID- 24098722
TI  - Phage display identification of CD100 in human atherosclerotic plaque macrophages
      and foam cells.
AB  - Atherosclerosis is a complex disease in which vessels develop plaques comprising
      dysfunctional endothelium, monocyte derived lipid laden foam cells and activated
      lymphocytes. Considering that humans and animal models of the disease develop
      quite distinct plaques, we used human plaques to search for proteins that could
      be used as markers of human atheromas. Phage display peptide libraries were
      probed to fresh human carotid plaques, and a bound phage homologous to plexin B1,
      a high affinity receptor for CD100, was identified. CD100 is a member of the
      semaphorin family expressed by most hematopoietic cells and particularly by
      activated T cells. CD100 expression was analyzed in human plaques and normal
      samples. CD100 mRNA and protein were analyzed in cultured monocytes, macrophages
      and foam cells. The effects of CD100 in oxLDL-induced foam cell formation and in
      CD36 mRNA abundance were evaluated. Human atherosclerotic plaques showed strong
      labeling of CD100/SEMA4D. CD100 expression was further demonstrated in peripheral
      blood monocytes and in in vitro differentiated macrophages and foam cells, with
      diminished CD100 transcript along the differentiation of these cells. Incubation
      of macrophages with CD100 led to a reduction in oxLDL-induced foam cell formation
      probably through a decrease of CD36 expression, suggesting for the first time an
      atheroprotective role for CD100 in the human disease. Given its differential
      expression in the numerous foam cells and macrophages of the plaques and its
      capacity to decrease oxLDL engulfment by macrophages we propose that CD100 may
      have a role in atherosclerotic plaque development, and may possibly be employed
      in targeted treatments of these atheromas. 

PMID- 24098723
TI  - Drosophila XBP1 expression reporter marks cells under endoplasmic reticulum
      stress and with high protein secretory load.
AB  - Expression of genes in the endoplasmic reticulum (ER) beyond its protein folding
      capacity activates signaling pathways that are collectively referred to as the
      Unfolded Protein Response (UPR). A major branch of the UPR pathway is mediated by
      IRE1, an ER-tethered endonuclease. Upon ER stress-induced activation, IRE1
      splices the mRNA of XBP1, thereby generating an active isoform of this
      transcription factor. During normal Drosophila development, tissues with high
      protein secretory load show signs of IRE1/XBP1 activity indicative of inherent ER
      stress associated with those cell types. Here, we report that the XBP1 promoter
      activity itself is enhanced in secretory tissues of Drosophila, and it can be
      induced by excessive ER stress. Specifically, we developed a Drosophila XBP1
      transcription reporter by placing dsRed under the control of the XBP1 intergenic
      sequence. DsRed expression in these xbp1p>dsRed transgenic flies showed patterns
      similar to that of xbp1 transcript distribution. In healthy developing flies, the
      reporter expression was highest in salivary glands and the intestine. In the
      adult, the male reproductive organs showed high levels of dsRed. These tissues
      are known to have high protein secretory load. Consistently, the xbp1p>dsRed
      reporter was induced by excessive ER stress caused by mutant Rhodopsin-1
      overexpression. These results suggest that secretory cells suffer from inherent
      ER stress, and the xbp1p>dsRed flies provide a useful tool in studying the
      function and homeostasis of those cells. 

PMID- 24098724
TI  - 20-years of population-based cancer registration in hepatitis B and liver cancer
      prevention in the Gambia, West Africa.
AB  - BACKGROUND: The Gambia Hepatitis Intervention Study (GHIS) was designed as a
      randomised control trial of infant hepatitis B vaccination applied to public
      health policy, with the main goal of preventing primary liver cancer later in
      adult life in The Gambia. To that effect, the National Cancer Registry of The
      Gambia (NCR), a population-based cancer registry (PBCR), was established in 1986
      to actively collect data on all cancer diagnosis nation-wide. We extracted 20
      years (1990-2009) of data to assess for the first time, the evolution of the most
      common cancers, also describe and demonstrate the role of the PBCR in a hepatitis
      B and liver cancer prevention programme in this population. METHODS AND FINDINGS:
      We estimated Age-Standardised Incidence Rates (ASR (W)) of the most common
      cancers registered during the period by gender. The registration period was
      divided into four 5-year intervals and incidence rates were estimated for each
      interval. The most common cancers in males were liver, prostate, lung plus
      bronchus, non-Hodgkin lymphoma (NHL) and stomach, accounting for 60%, 5%, 4%, 5%
      and 3%, respectively. Similarly, cancers of the cervix uteri, liver, breast and
      NHL, were the most common in females, accounting for 33%, 24%, 11% and 4% of the
      female cancers, respectively. CONCLUSIONS: Cancer incidence has remained
      relatively stable over time, but as shown elsewhere in sub-Saharan Africa the
      disease is a threat in The Gambia. The infection related cancers which are mostly
      preventable (HBV in men and HPV/HIV in women) were the most common. At the moment
      the data is not enough to detect an effect of hepatitis B vaccination on liver
      cancer incidence in The Gambia. However, we observed that monitoring case
      occurrence through PBCR is a key public health pre-requisite for rational
      planning and implementation of targeted interventions for improving the health of
      the population.

PMID- 24098725
TI  - Metagenomic screening for aromatic compound-responsive transcriptional
      regulators.
AB  - We applied a metagenomics approach to screen for transcriptional regulators that
      sense aromatic compounds. The library was constructed by cloning environmental
      DNA fragments into a promoter-less vector containing green fluorescence protein.
      Fluorescence-based screening was then performed in the presence of various
      aromatic compounds. A total of 12 clones were isolated that fluoresced in
      response to salicylate, 3-methyl catechol, 4-chlorocatechol and
      chlorohydroquinone. Sequence analysis revealed at least 1 putative
      transcriptional regulator, excluding 1 clone (CHLO8F). Deletion analysis
      identified compound-specific transcriptional regulators; namely, 8 LysR-types, 2
      two-component-types and 1 AraC-type. Of these, 9 representative clones were
      selected and their reaction specificities to 18 aromatic compounds were
      investigated. Overall, our transcriptional regulators were functionally diverse
      in terms of both specificity and induction rates. LysR- and AraC- type regulators
      had relatively narrow specificities with high induction rates (5-50 fold),
      whereas two-component-types had wide specificities with low induction rates (3
      fold). Numerous transcriptional regulators have been deposited in sequence
      databases, but their functions remain largely unknown. Thus, our results add
      valuable information regarding the sequence-function relationship of
      transcriptional regulators. 

PMID- 24098726
TI  - Phytotoxicity of four photosystem II herbicides to tropical seagrasses.
AB  - Coastal waters of the Great Barrier Reef (GBR) are contaminated with agricultural
      pesticides, including the photosystem II (PSII) herbicides which are the most
      frequently detected at the highest concentrations. Designed to control weeds,
      these herbicides are equally potent towards non-target marine species, and the
      close proximity of seagrass meadows to flood plumes has raised concerns that
      seagrasses may be the species most threatened by herbicides from runoff. While
      previous work has identified effects of PSII herbicides on the photophysiology,
      growth and mortality in seagrass, there is little comparative quantitative
      toxicity data for seagrass. Here we applied standard ecotoxicology protocols to
      quantify the concentrations of four priority PSII herbicides that inhibit
      photochemistry by 10, 20 and 50% (IC10, IC20 and IC50) over 72 h in two common
      seagrass species from the GBR lagoon. The photosystems of seagrasses
      Zosteramuelleri and Haloduleuninervis were shown to be generally more sensitive
      to the PSII herbicides Diuron, Atrazine, Hexazinone and Tebuthiuron than corals
      and tropical microalgae. The herbicides caused rapid inhibition of effective
      quantum yield (?F/F m '), indicating reduced photosynthesis and maximum effective
      yields (Fv/Fm ) corresponding to chronic damage to PSII. The PSII herbicide
      concentrations which affected photosynthesis have been exceeded in the GBR lagoon
      and all of the herbicides inhibited photosynthesis at concentrations lower than
      current marine park guidelines. There is a strong likelihood that the impacts of
      light limitation from flood plumes and reduced photosynthesis from PSII
      herbicides exported in the same waters would combine to affect seagrass
      productivity. Given that PSII herbicides have been demonstrated to affect
      seagrass at environmental concentrations, we suggest that revision of
      environmental guidelines and further efforts to reduce PSII herbicide
      concentrations in floodwaters may both help protect seagrass meadows of the GBR
      from further decline. 

PMID- 24098727
TI  - Characterisation of the p53-mediated cellular responses evoked in primary mouse
      cells following exposure to ultraviolet radiation.
AB  - Exposure to ultraviolet (UV) light can cause significant damage to mammalian
      cells and, although the spectrum of damage produced varies with the wavelength of
      UV, all parts of the UV spectrum are recognised as being detrimental to human
      health. Characterising the cellular response to different wavelengths of UV
      therefore remains an important aim so that risks and their moderation can be
      evaluated, in particular in relation to the initiation of skin cancer. The p53
      tumour suppressor protein is central to the cellular response that protects the
      genome from damage by external agents such as UV, thus reducing the risk of
      tumorigenesis. In response to a variety of DNA damaging agents including UV
      light, wild-type p53 plays a role in mediating cell-cycle arrest, facilitating
      apoptosis and stimulating repair processes, all of which prevent the propagation
      of potentially mutagenic defects. In this study we examined the induction of p53
      protein and its influence on the survival of primary mouse fibroblasts exposed to
      different wavelengths of UV light. UVC was found to elevate p53 protein and its
      sequence specific DNA binding capacity. Unexpectedly, UVA treatment failed to
      induce p53 protein accumulation or sequence specific DNA binding. Despite this,
      UVA exposure of wild-type cells induced a p53 dependent G1 cell cycle arrest
      followed by a wave of p53 dependent apoptosis, peaking 12 hours post-insult.
      Thus, it is demonstrated that the elements of the p53 cellular response evoked by
      exposure to UV radiation are wavelength dependent. Furthermore, the
      interrelationship between various endpoints is complex and not easily
      predictable. This has important implications not only for understanding the mode
      of action of p53 but also for the use of molecular endpoints in quantifying
      exposure to different wavelengths of UV in the context of human health
      protection. 

PMID- 24098728
TI  - Control of the rescue and replication of Semliki Forest virus recombinants by the
      insertion of miRNA target sequences.
AB  - Due to their broad cell- and tissue-tropism, alphavirus-based replication
      competent vectors are of particular interest for anti-cancer therapy. These
      properties may, however, be potentially hazardous unless the virus infection is
      controlled. While the RNA genome of alphaviruses precludes the standard control
      techniques, host miRNAs can be used to down-regulate viral replication. In this
      study, target sites from ubiquitous miRNAs and those of miRNAs under-represented
      in cervical cancer cells were inserted into replication-competent DNA/RNA layered
      vectors of Semliki Forest virus. It was found that in order to achieve the most
      efficient suppression of recombinant virus rescue, the introduced target
      sequences must be fully complementary to those of the corresponding miRNAs.
      Target sites of ubiquitous miRNAs, introduced into the 3' untranslated region of
      the viral vector, profoundly reduced the rescue of recombinant viruses. Insertion
      of the same miRNA targets into coding region of the viral vector was
      approximately 300-fold less effective. Viruses carrying these miRNAs were
      genetically unstable and rapidly lost the target sequences. This process was
      delayed, but not completely prevented, by miRNA inhibitors. Target sites of miRNA
      under-represented in cervical cancer cells had much smaller but still significant
      effects on recombinant virus rescue in cervical cancer-derived HeLa cells. Over
      expression of miR-214, one of these miRNAs, reduced replication of the targeted
      virus. Though the majority of rescued viruses maintained the introduced miRNA
      target sequences, genomes with deletions of these sequences were also detected.
      Thus, the low-level repression of rescue and replication of targeted virus in
      HeLa cells was still sufficient to cause genetic instability. 

PMID- 24098729
TI  - Structural diversity of class 1 integrons and their associated gene cassettes in
      Klebsiella pneumoniae isolates from a hospital in China.
AB  - BACKGROUND: Klebsiella pneumoniae strains carrying class 1 integrons are becoming
      more common worldwide, and their role in the dissemination of drug resistance is
      significant. The aim of this study was to characterize the structural diversity
      of class 1 integrons and their associated gene cassettes in K. pneumoniae
      isolates from hospital settings. METHODOLOGY/PRINCIPAL FINDINGS: We analyzed a
      total of 176 K. pneumoniae isolates in a tertiary-care hospital in Beijing, China
      for the period of November 1, 2010-October 31, 2011. The presence of class 1
      integrons and gene cassettes was analyzed by PCR and sequencing. The prevalence
      of class 1 integrons was 51.1% (90/176). Fourteen different gene cassettes and 10
      different gene cassette arrays were detected. dfrA and aadA cassettes were
      predominant and cassette combination dfrA1-orfC was most frequently found (13.6%,
      24/176). Strong association between resistance to a variety of drugs (both
      phenotypes and the associated genes) and the presence of class 1 integrons was
      observed. In addition, we also identified an association between some previously
      identified prevalent sequence types (such as ST11, ST15, ST147, ST562, and ST716)
      and the presence of class 1 integrons. CONCLUSIONS/SIGNIFICANCE: Data from this
      study demonstrated that class 1 integrons are highly diverse and are associated
      with a variety of drug resistance phenotypes, drug resistance genes, as well as
      genotypes among K. pneumoniae isolates. Continuous monitoring of gene cassettes
      in class 1 integrons is warranted to improve the understanding and control of
      drug resistance among hospital settings.

PMID- 24098730
TI  - The association of genetic markers for type 2 diabetes with prediabetic status -
      cross-sectional data of a diabetes prevention trial.
AB  - OBJECTIVE: To investigate the association of risk alleles for type 2 diabetes
      with prediabetes accounting for age, anthropometry, inflammatory markers and
      lifestyle habits. DESIGN: Cross-sectional study of 129 men and 157 women of
      medium-sized companies in northern Germany in the Delay of Impaired Glucose
      Tolerance by a Healthy Lifestyle Trial (DELIGHT). METHODS: Besides established
      risk factors, 41 single nucleotide polymorphisms (SNPs) that have previously been
      found to be associated with type 2 diabetes were analyzed. As a nonparametric
      test a random forest approach was used that allows processing of a large number
      of predictors. Variables with the highest impact were entered into a multivariate
      logistic regression model to estimate their association with prediabetes.
      RESULTS: Individuals with prediabetes were characterized by a slightly, but
      significantly higher number of type 2 diabetes risk alleles (42.5+/-4.1 vs.
      41.3+/-4.1, p = 0.013). After adjustment for age and waist circumference 6 SNPs
      with the highest impact in the random forest analysis were associated with risk
      for prediabetes in a logistic regression model. At least 5 of these SNPs were
      positively related to prediabetic status (odds ratio for prediabetes 1.57 per
      allele (Cl 1.21-2.10, p = 0.001)). CONCLUSIONS: This explorative analysis of data
      of DELIGHT demonstrates that at least 6 out of 41 genetic variants characteristic
      of individuals with type 2 diabetes may also be associated with prediabetes.
      Accumulation of these risk alleles may markedly increase the risk for
      prediabetes. However, prospective studies are required to corroborate these
      findings and to demonstrate the predictive value of these genetic variants for
      the risk to develop prediabetes.

PMID- 24098731
TI  - Revealing of Mycobacterium marinum transcriptome by RNA-seq.
AB  - Transcriptome analysis has played an essential role for revealing gene expression
      and the complexity of regulations at transcriptional level. RNA-seq is a powerful
      tool for transcriptome profiling, which uses deep-sequencing technologies to
      directly determine the cDNA sequence. Here, we utilized RNA-seq to explore the
      transcriptome of Mycobacteriummarinum (M. marinum), which is a useful model to
      study the pathogenesis of Mycobacterium tuberculosis (Mtb). Two profiles of
      exponential and early stationary phase cultures were generated after a physical
      ribosome RNA removal step. We systematically described the transcriptome and
      analyzed the functions for the differentiated expressed genes between the two
      phases. Furthermore, we predicted 360 operons throughout the whole genome, and 13
      out of 17 randomly selected operons were validated by qRT-PCR. In general, our
      study has primarily uncovered M. marinum transcriptome, which could help to gain
      a better understanding of the regulation system in Mtb that underlines disease
      pathogenesis. 

PMID- 24098732
TI  - The seed plant flora of the Mount Jinggangshan region, southeastern China.
AB  - The Mount Jinggangshan region is located between Jiangxi and Hunan provinces in
      southeastern China in the central section of the Luoxiao Mountains. A detailed
      investigation of Mount Jinggangshan region shows that the seed plant flora
      comprises 2,958 species in 1,003 genera and 210 families (Engler's system
      adjusted according to Zhengyi Wu's concept). Among them, 23 species of
      gymnospermae belong to 17 genera and 9 families, and 2,935 species of angiosperms
      are in 986 genera and 201 families. Moreover, they can also be sorted into woody
      plants (350 genera and 1,295 species) and herbaceous plants (653 genera and 1,663
      species). The dominant families are mainly Fagaceae, Lauraceae, Theaceae,
      Hamamelidaceae, Magnoliaceae, Ericaceae, Styracaceae, Aquifoliaceae,
      Elaeocarpaceae, Aceraceae, Rosaceae, Corylaceae, Daphniphyllaceae, Symplocaceae,
      Euphorbiaceae, Pinaceae, Taxodiaceae, Cupressaceae and Taxaceae. Ancient and
      relic taxa include Ginkgo biloba, Fokieniahodginsii, Amentotaxusargotaenia,
      Disanthuscercidifolia subsp. longipes, Hamamelismollis, Manglietiafordiana,
      Magnoliaofficinalis, Tsoongiodendronodorum, Fortuneariasinensis,
      Cyclocaryapaliurus, Eucommiaulmoides, Sargentodoxacuneata,
      Bretschneiderasinensis, Camptothecaacuminata, Tapisciasinensis, etc. The flora of
      Mount Jinggangshan region includes 79 cosmopolitan genera and 924 non
      cosmopolitan genera, which are 7.88% and 92.12% of all genera. The latter
      includes 452 tropical genera (48.92%) and 472 temperate genera (51.08%). The
      temperate elements include 44 genera endemic to China, accounting for 4.76% of
      all genera. Among 1,003 genera, 465 have only a single species and 401 are
      oligotypic genera (with 2-5 species). These genera account for 86.34% of all
      genera. The floristic analysis indicates that the flora of Mount Jinggangshan
      region is closely related to the flora of Mount Wuyishan region in southeastern
      China. The flora of Mount Jinggangshan region also contains many elements of
      central and southern China. Mount Jinggangshan region is an important north-south
      floristic passageway and is also a boundary between the floras of eastern,
      central and south China. 

PMID- 24098733
TI  - Phanta: a non-fluorescent photochromic acceptor for pcFRET.
AB  - We have developed an orange non-fluorescent photochromic protein (quantum yield,
      0.003) we call Phanta that is useful as an acceptor in pcFRET applications.
      Phanta can be repeatedly inter-converted between the two absorbing states by
      alternate exposure to cyan and violet light. The absorption spectra of Phanta in
      one absorbing state shows excellent overlap with the emission spectra of a number
      of donor green fluorescent proteins including the commonly used EGFP. We show
      that the Phanta-EGFP FRET pair is suitable for monitoring the activation of
      caspase 3 in live cells using readily available instrumentation and a simple
      protocol that requires the acquisition of two donor emission images corresponding
      to Phanta in each of its photoswitched states. This the first report of a
      genetically encoded non-fluorescent acceptor for pcFRET. 

PMID- 24098735
TI  - Evaluation of four endogenous reference genes and their real-time PCR assays for
      common wheat quantification in GMOs detection.
AB  - Proper selection of endogenous reference genes and their real-time PCR assays is
      quite important in genetically modified organisms (GMOs) detection. To find a
      suitable endogenous reference gene and its real-time PCR assay for common wheat
      (Triticum aestivum L.) DNA content or copy number quantification, four previously
      reported wheat endogenous reference genes and their real-time PCR assays were
      comprehensively evaluated for the target gene sequence variation and their real
      time PCR performance among 37 common wheat lines. Three SNPs were observed in the
      PKABA1 and ALMT1 genes, and these SNPs significantly decreased the efficiency of
      real-time PCR amplification. GeNorm analysis of the real-time PCR performance of
      each gene among common wheat lines showed that the Waxy-D1 assay had the lowest M
      values with the best stability among all tested lines. All results indicated that
      the Waxy-D1 gene and its real-time PCR assay were most suitable to be used as an
      endogenous reference gene for common wheat DNA content quantification. The
      validated Waxy-D1 gene assay will be useful in establishing accurate and
      creditable qualitative and quantitative PCR analysis of GM wheat. 

PMID- 24098734
TI  - Fearful foragers: honey bees tune colony and individual foraging to multi
      predator presence and food quality.
AB  - Fear can have strong ecosystem effects by giving predators a role
      disproportionate to their actual kill rates. In bees, fear is shown through
      foragers avoiding dangerous food sites, thereby reducing the fitness of
      pollinated plants. However, it remains unclear how fear affects pollinators in a
      complex natural scenario involving multiple predator species and different patch
      qualities. We studied hornets, Vespa velutina (smaller) and V. tropica (bigger)
      preying upon the Asian honey bee, Apis cerana in China. Hornets hunted bees on
      flowers and were attacked by bee colonies. Bees treated the bigger hornet species
      (which is 4 fold more massive) as more dangerous. It received 4.5 fold more
      attackers than the smaller hornet species. We tested bee responses to a three
      feeder array with different hornet species and varying resource qualities. When
      all feeders offered 30% sucrose solution (w/w), colony foraging allocation,
      individual visits, and individual patch residence times were reduced according to
      the degree of danger. Predator presence reduced foraging visits by 55-79% and
      residence times by 17-33%. When feeders offered different reward levels (15%,
      30%, or 45% sucrose), colony and individual foraging favored higher sugar
      concentrations. However, when balancing food quality against multiple threats
      (sweeter food corresponding to higher danger), colonies exhibited greater fear
      than individuals. Colonies decreased foraging at low and high danger patches.
      Individuals exhibited less fear and only decreased visits to the high danger
      patch. Contrasting individual with emergent colony-level effects of fear can thus
      illuminate how predators shape pollination by social bees. 

PMID- 24098736
TI  - Loss of innervation and axon plasticity accompanies impaired diabetic wound
      healing.
AB  - Loss of cutaneous innervation from sensory neuropathy is included among
      mechanisms for impaired healing of diabetic skin wounds. The relationships
      between cutaneous axons and their local microenvironment during wound healing are
      challenged in diabetes. Here, we show that secondary wound closure of the hairy
      dorsal skin of mice is delayed by diabetes and is associated with not only a pre
      existing loss of cutaneous axons but substantial retraction of axons around the
      wound. At 7d following a 3mm punch wound, a critical period of healing and
      reinnervation, both intact skin nearby the wound and skin directly at the wound
      margins had over 30-50% fewer axons and a larger deficit of ingrowing axons in
      diabetics. These findings contrasted with a pre-existing 10-15% deficit in axons.
      Moreover, new diabetic ingrowing axons had less evidence of plasticity.
      Unexpectedly, hair follicles adjacent to the wounds had a 70% reduction in their
      innervation associated with depleted expression of hair follicular stem cell
      markers. These impairments were associated with the local upregulation of two
      established axon regenerative 'roadblocks': PTEN and RHOA, potential but thus far
      unexplored mediators of these changes. The overall findings identify striking and
      unexpected superimposed cutaneous axon loss or retraction beyond that expected of
      diabetic neuropathy alone, associated with experimental diabetic skin wounding, a
      finding that prompts new considerations in diabetic wounds. 

PMID- 24098737
TI  - Four microRNAs promote prostate cell proliferation with regulation of PTEN and
      its downstream signals in vitro.
AB  - BACKGROUND: Phosphatase and tensin homologue (PTEN), as a tumor suppressor, plays
      vital roles in tumorigenesis and progression of prostate cancer. However, the
      mechanisms of PTEN regulation still need further investigation. We here report
      that a combination of four microRNAs (miR-19b, miR-23b, miR-26a and miR-92a)
      promotes prostate cell proliferation by regulating PTEN and its downstream
      signals in vitro. METHODOLOGY/PRINCIPAL FINDINGS: We found that the four
      microRNAs (miRNAs) could effectively suppress PTEN expression by directly
      interacting with its 3' UTR in prostate epithelial and cancer cells. Under
      expression of the four miRNAs by antisense neutralization up-regulates PTEN
      expression, while overexpression of the four miRNAs accelerates epithelial and
      prostate cancer cell proliferation. Furthermore, the expression of the four
      miRNAs could, singly or jointly, alter the expression of the key components in
      the phosphoinositide 3-kinase (PI3K)/Akt pathway, including PIK3CA, PIK3CD,
      PIK3R1 and Akt, along with their downstream signal, cyclin D1. CONCLUSIONS: These
      results suggested that the four miRNAs could promote prostate cancer cell
      proliferation by co-regulating the expression of PTEN, PI3K/Akt pathway and
      cyclin D1 in vitro. These findings increase understanding of the molecular
      mechanisms of prostate carcinogenesis and progression, even provide valuable
      insights into the diagnosis, prognosis, and rational design of novel therapeutics
      for prostate cancer.

PMID- 24098738
TI  - New specimens of the rare taeniodont Wortmania (Mammalia: Eutheria) from the San
      Juan Basin of New Mexico and comments on the phylogeny and functional morphology
      of "archaic" mammals.
AB  - BACKGROUND: Taeniodonta is a clade of Late Cretaceous-Paleogene mammals
      remarkable for their relatively extreme cranial, dental, and postcranial
      adaptations and notable for being among the first mammals to achieve relatively
      large size following the Cretaceous-Paleogene mass extinction. Previous workers
      have hypothesized that taeniodonts can be divided into two clades: Conoryctidae,
      a group of small-bodied taeniodonts with supposedly "generalized" postcranial
      skeletons, and Stylinodontidae, a group of large-bodied, robust animals with
      massive forelimbs and claws adapted for scratch-digging. However, many taeniodont
      taxa are poorly known and few are represented by postcranial material, leaving
      many details about their anatomy, biology, and evolution ambiguous.
      METHODOLOGY/PRINCIPAL FINDINGS: In this paper, we describe three new specimens of
      the rare taxon Wortmania otariidens from the early Paleocene (Puercan) of New
      Mexico. Among these specimens is one that includes remarkably complete cranial
      and dental material, including associated upper and lower teeth, and another that
      consists of partial forelimbs. These specimens allow for an updated anatomical
      description of this unusual taxon, supply new data for phylogenetic analyses, and
      enable a more constrained discussion of taeniodont biology and functional
      morphology. CONCLUSIONS/SIGNIFICANCE: The new specimen of Wortmania that includes
      associated upper and lower teeth indicates that previous interpretations of the
      upper dentition of this taxon were not accurate and the taxon Robertschochia
      sullivani is a junior synonym of W. otariidens. New specimens that include
      partial forelimbs indicate that Wortmania is very similar to later, large-bodied
      taeniodonts, with marked and distinctive adaptations for scratch-digging.
      Comparisons with other taeniodont taxa that include postcranial material suggest
      that all taeniodonts may have had scratch-digging adaptations. A phylogenetic
      analysis shows that Schowalteria and Onychodectes are basal taeniodonts,
      Stylinodontidae (including Wortmania) is monophyletic, and a monophyletic
      Conoryctidae (but not including Onychodectes) is only recovered when certain
      characters are ordered.

PMID- 24098739
TI  - Pest and disease management: why we shouldn't go against the grain.
AB  - Given the wide range of scales and mechanisms by which pest or disease agents
      disperse, it is unclear whether there might exist a general relationship between
      scale of host heterogeneity and spatial spread that could be exploited by
      available management options. In this model-based study, we investigate the
      interaction between host distributions and the spread of pests and diseases using
      an array of models that encompass the dispersal and spread of a diverse range of
      economically important species: a major insect pest of coniferous forests in
      western North America, the mountain pine beetle (Dendroctonus ponderosae); the
      bacterium Pseudomonas syringae, one of the most-widespread and best-studied
      bacterial plant pathogens; the mosquito Culex erraticus, an important vector for
      many human and animal pathogens, including West Nile Virus; and the oomycete
      Phytophthora infestans, the causal agent of potato late blight. Our model results
      reveal an interesting general phenomenon: a unimodal ('humpbacked') relationship
      in the magnitude of infestation (an index of dispersal or population spread) with
      increasing grain size (i.e., the finest scale of patchiness) in the host
      distribution. Pest and disease management strategies targeting different aspects
      of host pattern (e.g., abundance, aggregation, isolation, quality) modified the
      shape of this relationship, but not the general unimodal form. This is a
      previously unreported effect that provides insight into the spatial scale at
      which management interventions are most likely to be successful, which, notably,
      do not always match the scale corresponding to maximum infestation. Our findings
      could provide a new basis for explaining historical outbreak events, and have
      implications for biosecurity and public health preparedness. 

PMID- 24098740
TI  - Dynamic trans interactions in yeast chromosomes.
AB  - Three-dimensional organization of the genome is important for regulation of gene
      expression and maintenance of genomic stability. It also defines, and is defined
      by, contacts between different chromosomal loci. Interactions between loci
      positioned on different chromosomes, i.e. "trans" interactions are one type of
      such contacts. Here, we describe a case of inducible trans interaction in
      chromosomes of the budding yeast S. cerevisiae. Special DNA sequences, inserted
      in two ectopic chromosomal loci positioned in trans, pair with one another in an
      inducible manner. The spatial proximity diagnostic of pairing is observable by
      both chromosome capture analysis (3C) and epifluorescence microscopy in whole
      cells. Protein synthesis de novo appears to be required for this process. The
      three-dimensional organization of the yeast nucleus imposes a constraint on such
      pairing, presumably by dictating the probability with which the two sequences
      collide with one another. 

PMID- 24098741
TI  - Weighted SNP set analysis in genome-wide association study.
AB  - Genome-wide association studies (GWAS) are popular for identifying genetic
      variants which are associated with disease risk. Many approaches have been
      proposed to test multiple single nucleotide polymorphisms (SNPs) in a region
      simultaneously which considering disadvantages of methods in single locus
      association analysis. Kernel machine based SNP set analysis is more powerful than
      single locus analysis, which borrows information from SNPs correlated with causal
      or tag SNPs. Four types of kernel machine functions and principal component based
      approach (PCA) were also compared. However, given the loss of power caused by low
      minor allele frequencies (MAF), we conducted an extension work on PCA and used a
      new method called weighted PCA (wPCA). Comparative analysis was performed for
      weighted principal component analysis (wPCA), logistic kernel machine based test
      (LKM) and principal component analysis (PCA) based on SNP set in the case of
      different minor allele frequencies (MAF) and linkage disequilibrium (LD)
      structures. We also applied the three methods to analyze two SNP sets extracted
      from a real GWAS dataset of non-small cell lung cancer in Han Chinese population.
      Simulation results show that when the MAF of the causal SNP is low, weighted
      principal component and weighted IBS are more powerful than PCA and other kernel
      machine functions at different LD structures and different numbers of causal
      SNPs. Application of the three methods to a real GWAS dataset indicates that wPCA
      and wIBS have better performance than the linear kernel, IBS kernel and PCA. 

PMID- 24098742
TI  - The ether lipid precursor hexadecylglycerol causes major changes in the lipidome
      of HEp-2 cells.
AB  - The ether-lipid precursor sn-1-O-hexadecylglycerol (HG) can be used to compensate
      for early metabolic defects in ether-lipid biosynthesis. To investigate a
      possible metabolic link between ether-linked phospholipids and the rest of the
      cellular lipidome, we incubated HEp-2 cells with HG. Mass spectrometry analysis
      revealed major changes in the lipidome of HG-treated cells compared to that of
      untreated cells or cells treated with palmitin, a control substance for HG
      containing an acyl group instead of the ether group. We present quantitative data
      for a total of 154 species from 17 lipid classes. These species are those
      constituting more than 2% of their lipid class for most lipid classes, but more
      than 1% for the ether lipids and glycosphingolipids. In addition to the expected
      ability of HG to increase the levels of ether-linked glycerophospholipids with 16
      carbon atoms in the sn-1 position, this precursor also decreased the amounts of
      glycosphingolipids and increased the amounts of ceramide, phosphatidylinositol
      and lysophosphatidylinositol. However, incubation with palmitin, the fatty acyl
      analogue of HG, also increased the amounts of ceramide and phosphatidylinositols.
      Thus, changes in these lipid classes were not ether lipid-dependent. No major
      effects were observed for the other lipid classes, and cellular functions such as
      growth and endocytosis were unaffected. The data presented clearly demonstrate
      the importance of performing detailed quantitative lipidomic studies to reveal
      how the metabolism of ether-linked glycerophospholipids is coupled to that of
      glycosphingolipids and ester-linked glycerophospholipids, especially
      phosphatidylinositols. 

PMID- 24098743
TI  - Systems-based approaches to probing metabolic variation within the Mycobacterium
      tuberculosis complex.
AB  - The Mycobacterium tuberculosis complex includes bovine and human strains of the
      tuberculosis bacillus, including Mycobacterium tuberculosis, Mycobacterium bovis
      and the Mycobacterium bovis BCG vaccine strain. M. bovis has evolved from a M.
      tuberculosis-like ancestor and is the ancestor of the BCG vaccine. The pathogens
      demonstrate distinct differences in virulence, host range and metabolism, but the
      role of metabolic differences in pathogenicity is poorly understood. Systems
      biology approaches have been used to investigate the metabolism of M.
      tuberculosis, but not to probe differences between tuberculosis strains. In this
      study genome scale metabolic networks of M. bovis and M. bovis BCG were
      constructed and interrogated, along with a M. tuberculosis network, to predict
      substrate utilisation, gene essentiality and growth rates. The models correctly
      predicted 87-88% of high-throughput phenotype data, 75-76% of gene essentiality
      data and in silico-predicted growth rates matched measured rates. However,
      analysis of the metabolic networks identified discrepancies between in silico
      predictions and in vitro data, highlighting areas of incomplete metabolic
      knowledge. Additional experimental studies carried out to probe these
      inconsistencies revealed novel insights into the metabolism of these strains. For
      instance, that the reduction in metabolic capability observed in bovine
      tuberculosis strains, as compared to M. tuberculosis, is not reflected by current
      genetic or enzymatic knowledge. Hence, the in silico networks not only
      successfully simulate many aspects of the growth and physiology of these
      mycobacteria, but also provide an invaluable tool for future metabolic studies. 

PMID- 24098744
TI  - Mannosylated lipoarabinomannans from Mycobacterium avium subsp. paratuberculosis
      alters the inflammatory response by bovine macrophages and suppresses killing of
      Mycobacterium avium subsp. avium organisms.
AB  - Analysis of the mechanisms through which pathogenic mycobacteria interfere with
      macrophage activation and phagosome maturation have shown that engagement of
      specific membrane receptors with bacterial ligands is the initiating event.
      Mannosylated lipoarabinomannan (Man-LAM) has been identified as one of the
      ligands that modulates macrophage function. We evaluated the effects of Man-LAM
      derived from Mycobacterium avium subsp. paratuberculosis (MAP) on bovine
      macrophages. Man-LAM induced a rapid and prolonged expression of IL-10 message as
      well as transient expression of TNF-alpha. Preincubation with Man-LAM for up to
      16 h did not suppress expression of IL-12 in response to interferon-gamma.
      Evaluation of the effect of Man-LAM on phagosome acidification, phagosome
      maturation, and killing of Mycobacterium avium subsp. avium (MAA) showed that
      preincubation of macrophages with Man-LAM before addition of MAA inhibited
      phagosome acidification, phagolysosome fusion, and reduced killing. Analysis of
      signaling pathways provided indirect evidence that inhibition of killing was
      associated with activation of the MAPK-p38 signaling pathway but not the pathway
      involved in regulation of expression of IL-10. These results support the
      hypothesis that MAP Man-LAM is one of the virulence factors facilitating survival
      of MAP in macrophages. 

PMID- 24098745
TI  - Menopausal symptoms among breast cancer patients: a potential indicator of
      favorable prognosis.
AB  - Menopausal symptoms have been suggested to be an indicator of better prognosis
      among patients treated for breast cancer, because women who experience these
      symptoms usually have a lower level of estrogen. We tested this hypothesis in a
      population-based, prospective cohort study involving 4,842 women with stage 0 to
      III primary breast cancer who were enrolled in the Shanghai Breast Cancer
      Survival Study between March 2002 and April 2006, were aged 20 to 75 years, and
      were recruited 6 months post-diagnosis. They were followed-up by in-person
      surveys and record linkages with the vital statistics registry. Cox regression
      analysis was used to evaluate the association of menopausal symptoms at baseline
      with breast cancer recurrence. Approximately 56% of patients experienced at least
      one menopausal symptom, including hot flashes, night sweats, and/or vaginal
      dryness at baseline. During a median follow-up period of 5.3 years, 720 women had
      a recurrence. Experiencing hot flashes or having >=2 menopausal symptoms was
      associated with lower risk of recurrence among premenopausal women (hazard ratio
      [HR]=0.77, 95% confidence interval [CI]: 0.62-0.96 for hot flashes; 0.73, 0.56
      0.96 for >=2 menopausal symptoms). Lower recurrence risk in relation to hot
      flashes was also observed among women who were not overweight/obese (HR=0.78, 95%
      CI: 0.64-0.99), those with relatively low waist-to-hip ratio (WHR) (HR=0.77, 95%
      CI: 0.61-0.97), and those who used tamoxifen (HR=0.75, 95% CI: 0.58-0.98).
      Consistently experiencing multiple menopausal symptoms was associated with lower
      recurrence risk among women with low WHR or who used tamoxifen. This large,
      population-based cohort study of women with breast cancer confirms that
      experiencing menopausal symptoms is an indicator of favorable breast cancer
      prognosis. 

PMID- 24098746
TI  - A systematic review of biochar research, with a focus on its stability in situ
      and its promise as a climate mitigation strategy.
AB  - BACKGROUND: Claims about the environmental benefits of charring biomass and
      applying the resulting "biochar" to soil are impressive. If true, they could
      influence land management worldwide. Alleged benefits include increased crop
      yields, soil fertility, and water-holding capacity; the most widely discussed
      idea is that applying biochar to soil will mitigate climate change. This claim
      rests on the assumption that biochar persists for hundreds or thousands of years,
      thus storing carbon that would otherwise decompose. We conducted a systematic
      review to quantify research effort directed toward ten aspects of biochar and
      closely evaluated the literature concerning biochar's stability. FINDINGS: We
      identified 311 peer-reviewed research articles published through 2011. We found
      very few field studies that addressed biochar's influence on several ecosystem
      processes: one on soil nutrient loss, one on soil contaminants, six concerning
      non-CO2 greenhouse gas (GHG) fluxes (some of which fail to support claims that
      biochar decreases non-CO2 GHG fluxes), and 16-19 on plants and soil properties.
      Of 74 studies related to biochar stability, transport or fate in soil, only seven
      estimated biochar decomposition rates in situ, with mean residence times ranging
      from 8 to almost 4,000 years. CONCLUSIONS: Our review shows there are not enough
      data to draw conclusions about how biochar production and application affect
      whole-system GHG budgets. Wide-ranging estimates of a key variable, biochar
      stability in situ, likely result from diverse environmental conditions,
      feedstocks, and study designs. There are even fewer data about the extent to
      which biochar stimulates decomposition of soil organic matter or affects non-CO2
      GHG emissions. Identifying conditions where biochar amendments yield favorable
      GHG budgets requires a systematic field research program. Finally, evaluating
      biochar's suitability as a climate mitigation strategy requires comparing its
      effects with alternative uses of biomass and considering GHG budgets over both
      long and short time scales.

PMID- 24098747
TI  - Antibody and T cell responses in reciprocal prime-boost studies with full-length
      and truncated merozoite surface protein 1-42 vaccines.
AB  - The P. falciparum Merozoite Surface Protein 1-42 (MSP1-42) is one of the most
      studied malaria subunit vaccine candidates. The N-terminal fragment of MSP1-42,
      MSP1-33, is primarily composed of allelic sequences, and has been shown to
      possess T helper epitopes that influence protective antibody responses toward the
      C-terminal region, MSP1-19. A truncated MSP1-42 vaccine, Construct 33-I,
      consisting of exclusively conserved T epitope regions of MSP1-33 expressed in
      tandem with MSP1-19, was previously shown to be a more effective immunogen than
      the full-length MSP1-42 vaccine. Here, by way of reciprocal priming/boosting
      immunization regimens, we studied the immunogenicity of Construct 33-I in the
      context of recognition by immune responses induced by the full-length native MSP1
      42 protein, in order to gauge the effects of pre- and post-exposures to MSP1-42
      on vaccine induced responses. Judging by immune responsiveness, antibody and T
      cell responses, Construct 33-I was effective as the priming antigen followed by
      full-length MSP1-42 boosting, as well as the boosting antigen following full
      length MSP1-42 priming. In particular, Construct 33-I priming elicited the
      broadest responsiveness in immunized animals subsequently exposed to MSP1-42.
      Moreover, Construct 33-I, with its conserved MSP1-33 specific T cell epitopes,
      was equally well recognized by homologous and heterologous allelic forms of MSP1
      42. Serum antibodies raised against Construct 33-I efficiently inhibited the
      growth of parasites carrying the heterologous MSP1-42 allele. These results
      suggest that Construct 33-I maintains and/or enhances its immunogenicity in an
      allelic or strain transcending fashion when deployed in populations having prior
      or subsequent exposures to native MSP1-42s. 

PMID- 24098748
TI  - Comparative effects of vasectomy surgery and buprenorphine treatment on faecal
      corticosterone concentrations and behaviour assessed by manual and automated
      analysis methods in C57 and C3H mice.
AB  - Establishing effective cage-side pain assessment methods is essential if post
      surgical pain is to be controlled effectively in laboratory animals. Changes to
      overall activity levels are the most common methods of assessment, but may not be
      the most appropriate for establishing the analgesic properties of drugs,
      especially in mice, due their high activity levels. Use of drugs that can affect
      activity (e.g. opioids) is also a problem. The relative merits of both manual and
      automated behaviour data collection methods was determined in two inbred mouse
      strains undergoing vasectomy following treatment with one of 2 buprenorphine dose
      rates. Body weights and the effects of surgery and buprenorphine on faecal
      corticosterone were also measured. Surgery caused abnormal behaviour and reduced
      activity levels, but high dose buprenorphine caused such large-scale increases in
      activity in controls that we could not establish analgesic effects in surgery
      groups. Only pain-specific behaviour scoring using the manual approach was
      effective in showing 0.05 mg/kg buprenorphine alleviated post-vasectomy pain. The
      C57 mice also responded better to buprenorphine than C3H mice, indicating they
      were either less painful, or more responsive to its analgesic effects. C3H mice
      were more susceptible to the confounding effects of buprenorphine irrespective of
      whether data were collected manually or via the automated approach. Faecal
      corticosterone levels, although variable, were higher in untreated surgery mice
      than in control groups, also indicating the presence of pain or distress. Pain
      specific scoring was superior to activity monitoring for assessing the analgesic
      properties of buprenorphine in vasectomised mice. Buprenorphine (0.01 mg/kg), in
      these strains of male mice, for this procedure, provided inadequate analgesia and
      although 0.05 mg/kg was more effective, not completely so. The findings support
      the recommendation that analgesic dose rates should be adjusted in relation to
      the potential severity of the surgical procedure, the mouse strain, and the
      individual animals' response. 

PMID- 24098749
TI  - Brain imaging of vesicular monoamine transporter type 2 in healthy aging subjects
      by 18F-FP-(+)-DTBZ PET.
AB  - (18)F-FP-(+)-DTBZ is a novel PET radiotracer targeting vesicular monoamine
      transporter type 2 (VMAT2). The goal was to explore the image features in normal
      human brains with (18)F-FP-(+)-DTBZ as a reference of molecular landmark for
      clinical diagnosis in Parkinson's disease (PD) and related disorders. MATERIALS
      AND METHODS: A total of 22 healthy subjects (59.3+/-6.0 years old) including 7
      men and 15 women were recruited for MRI and (18)F-FP-(+)-DTBZ PET scans. A total
      number of 55 brain VOIs were selected for quantitation analysis. The regional
      specific uptake ratio (SUR) was calculated with occipital as reference from MRI
      based spatially normalized (18)F-FP-(+)-DTBZ images. Regional percentage SUR to
      that of anterior putamen was calculated. Average SUR images were displayed in 2D
      and 3D space to illustrate the image patterns. The correlation between age and
      regional VMAT2 uptake was also examined. RESULTS: Visual assessment showed
      symmetric uptake of (18)F-FP-(+)-DTBZ and obviously highest in striatum, followed
      by nucleus accumbens, hypothalamus, substantia nigra, and raphe nuclei.
      Quantification analysis revealed striatal VMAT2 density of anterior
      putamen>posterior putamen>caudate nucleus. Other subcortical regions were with
      moderate VMAT2 distribution (6~51% SUR of anterior putamen), while slightly lower
      VMAT2 was observed in cerebellum (10.60% SUR) and much lower in neocortex (<5%
      SUR). No significant correlation of SUR to age was found in subcortical regions.
      CONCLUSION: Using (18)F-FP-(+)-DTBZ PET, we showed the 2D and 3D imaging features
      of the VMAT2 distribution in vivo in healthy aging brains. The in vivo imaging
      characteristics of VMAT2 is consistent with the expression of VMAT2 in a recent
      autopsy study. Therefore, 3D visualization and higher image quality of (18)F-FP
      (+)-DTBZ PET imaging might potentially be a powerful biomarker in detecting VMAT2
      distribution of subcortical regions, and for Parkinson's disease and related
      neuropsychiatric disorders involving related monoaminergic systems.

PMID- 24098750
TI  - Recombinant thrombomodulin protects mice against histone-induced lethal
      thromboembolism.
AB  - INTRODUCTION: Recent studies have shown that histones, the chief protein
      component of chromatin, are released into the extracellular space during sepsis,
      trauma, and ischemia-reperfusion injury, and act as major mediators of the death
      of an organism. This study was designed to elucidate the cellular and molecular
      basis of histone-induced lethality and to assess the protective effects of
      recombinant thrombomodulin (rTM). rTM has been approved for the treatment of
      disseminated intravascular coagulation (DIC) in Japan, and is currently
      undergoing a phase III clinical trial in the United States. METHODS: Histone H3
      levels in plasma of healthy volunteers and patients with sepsis and DIC were
      measured using enzyme-linked immunosorbent assay. Male C57BL/6 mice were injected
      intravenously with purified histones, and pathological examinations were
      performed. The protective effects of rTM against histone toxicity were analyzed
      both in vitro and in mice. RESULTS: Histone H3 was not detectable in plasma of
      healthy volunteers, but significant levels were observed in patients with sepsis
      and DIC. These levels were higher in non-survivors than in survivors.
      Extracellular histones triggered platelet aggregation, leading to thrombotic
      occlusion of pulmonary capillaries and subsequent right-sided heart failure in
      mice. These mice displayed symptoms of DIC, including thrombocytopenia, prolonged
      prothrombin time, decreased fibrinogen, fibrin deposition in capillaries, and
      bleeding. Platelet depletion protected mice from histone-induced death in the
      first 30 minutes, suggesting that vessel occlusion by platelet-rich thrombi might
      be responsible for death during the early phase. Furthermore, rTM bound to
      extracellular histones, suppressed histone-induced platelet aggregation,
      thrombotic occlusion of pulmonary capillaries, and dilatation of the right
      ventricle, and rescued mice from lethal thromboembolism. CONCLUSIONS:
      Extracellular histones cause massive thromboembolism associated with consumptive
      coagulopathy, which is diagnostically indistinguishable from DIC. rTM binds to
      histones and neutralizes the prothrombotic action of histones. This may
      contribute to the effectiveness of rTM against DIC.

PMID- 24098751
TI  - Expression analysis of an evolutionarily conserved alternative splicing factor,
      Sfrs10, in age-related macular degeneration.
AB  - Age-related macular degeneration (AMD) is the most common cause of blindness in
      the elderly population. Hypoxic stress created in the micro-environment of the
      photoreceptors is thought to be the underlying cause that results in the
      pathophysiology of AMD. However, association of AMD with alternative splicing
      mediated gene regulation is not well explored. Alternative Splicing is one of the
      primary mechanisms in humans by which fewer protein coding genes are able to
      generate a vast proteome. Here, we investigated the expression of a known stress
      response gene and an alternative splicing factor called Serine-Arginine rich
      splicing factor 10 (Sfrs10). Sfrs10 is a member of the serine-arginine (SR) rich
      protein family and is 100% identical at the amino acid level in most mammals.
      Immunoblot analysis on retinal extracts from mouse, rat, and chicken showed a
      single immunoreactive band. Further, immunohistochemistry on adult mouse, rat and
      chicken retinae showed pan-retinal expression. However, SFRS10 was not detected
      in normal human retina but was observed as distinct nuclear speckles in AMD
      retinae. This is in agreement with previous reports that show Sfrs10 to be a
      stress response gene, which is upregulated under hypoxia. The difference in the
      expression of Sfrs10 between humans and lower mammals and the upregulation of
      SFRS10 in AMD is further reflected in the divergence of the promoter sequence
      between these species. Finally, SFRS10+ speckles were independent of the SC35+ SR
      protein speckles or the HSF1+ stress granules. In all, our data suggests that
      SFRS10 is upregulated and forms distinct stress-induced speckles and might be
      involved in AS of stress response genes in AMD. 

PMID- 24098752
TI  - Specific mtDNA mutations in mouse carcinoma cells suppress their tumor formation
      via activation of the host innate immune system.
AB  - In mammalian species, mitochondrial DNA (mtDNA) with pathogenic mutations that
      induce mitochondrial respiration defects has been proposed to be involved in
      tumor phenotypes via induction of enhanced glycolysis under normoxic conditions
      (the Warburg effects). However, because both nuclear DNA and mtDNA control
      mitochondrial respiratory function, it is difficult to exclude the possible
      contribution of nuclear DNA mutations to mitochondrial respiration defects and
      the resultant expression of tumor phenotypes. Therefore, it is important to
      generate transmitochondrial cybrids sharing the same nuclear DNA background but
      carrying mtDNA with and without the mutations by using intercellular mtDNA
      transfer technology. Our previous studies isolated transmitochondrial cybrids and
      showed that specific mtDNA mutations enhanced tumor progression as a consequence
      of overproduction of reactive oxygen species (ROS). This study assessed whether
      mtDNA mutations inducing ROS overproduction always enhance tumor progression. We
      introduced mtDNA from senescence-accelerated mice P1 (SAMP1) into C57BL/6J (B6)
      mice-derived Lewis lung carcinoma P29 cells, and isolated new transmitochondrial
      cybrids (P29mtSAMP1 cybrids) that overproduced ROS. The inoculation of the
      cybrids into B6 mice unexpectedly showed that mtDNA from SAMP1 mice conversely
      induced tumor suppression. Moreover, the tumor suppression of P29mtSAMP1 cybrids
      in B6 mice occurred as a consequence of innate immune responses of the host B6
      mice. Enzyme pretreatment experiments of P29mtSAMP1 cybrids revealed that some
      peptides encoded by mtDNA and expressed on the cell surface of P29mtSAMP1 cybrids
      induce increased IL-6 production from innate immune cells (dendritic cells) of B6
      mice, and mediate augmented inflammatory responses around the tumor-inoculated
      environment. These observations indicate presence of a novel role of mtDNA in
      tumor phenotype, and provide new insights into the fields of mitochondrial tumor
      biology and tumor immunology. 

PMID- 24098753
TI  - Isoalantolactone inhibits UM-SCC-10A cell growth via cell cycle arrest and
      apoptosis induction.
AB  - Isoalantolactone is a sesquiterpene lactone compound isolated from the roots of
      Inula helenium L. Previous studies have demonstrated that isoalantolactone
      possesses antifungal, anti-bacterial, anti-helminthic and anti-proliferative
      properties in a variety of cells, but there are no studies concerning its effects
      on head and neck squamous cell carcinoma (HNSCC). In the present study, an MTT
      assay demonstrated that isoalantolactone has anti-proliferative activity against
      the HNSCC cell line (UM-SCC-10A). Immunostaining identified that this compound
      induced UM-SCC-10A cell apoptosis but not necrosis. To explain the molecular
      mechanisms underlying its effects, flow cytometry and western blot analysis
      showed that the apoptosis was associated with cell cycle arrest during the G1
      phase, up-regulation of p53 and p21, and down-regulation of cyclin D.
      Furthermore, our results revealed that induction of apoptosis through a
      mitochondrial pathway led to up-regulation of pro-apoptotic protein expression
      (Bax), down-regulation of anti-apoptotic protein expression (Bcl-2),
      mitochondrial release of cytochrome c (Cyto c), reduction of mitochondrial
      membrane potential (MMP) and activation of caspase-3 (Casp-3). Involvement of the
      caspase apoptosis pathway was confirmed using caspase inhibitor Z-VAD-FMK
      pretreatment. Together, our findings suggest that isoalantolactone induced
      caspase-dependent apoptosis via a mitochondrial pathway and was associated with
      cell cycle arrest in the G1 phase in UM-SCC-10A cells. Therefore,
      isoalantolactone may become a potential drug for treating HNSCC. 

PMID- 24098754
TI  - Chlorogenic acid inhibits the replication and viability of enterovirus 71 in
      vitro.
AB  - Enterovirus 71 (EV71) is an etiology for a number of diseases in humans.
      Traditional Chinese herbs have been reported to be effective for treating EV71
      infection. However, there is no report about the antiviral effects of CHA against
      EV71. In this study, plaque reduction assay demonstrated that the inhibitory
      concentration 50% (IC50) of CHA on EV71 replication is 6.3 ug/ml. When both CHA
      (20 ug/ml) and EV71 were added, or added post-infection at different time points,
      CHA was able to effectively inhibit EV71 replication between 0 and 10 h. In
      addition, CHA inhibited EV71 2A transcription and translation in EV71-infected RD
      cells, but did not affect VP1, 3C, and 3D expression. Furthermore, CHA inhibited
      secretions of IL-6, TNF-alpha, IFN-gamma and MCP-1 in EV71-infected RD cells.
      Altogether, these results revealed that CHA may have antiviral properties for
      treating EV71 infection. 

PMID- 24098755
TI  - Regorafenib effects on human colon carcinoma xenografts monitored by dynamic
      contrast-enhanced computed tomography with immunohistochemical validation.
AB  - OBJECTIVE: To investigate dynamic contrast-enhanced computed tomography for
      monitoring the effects of regorafenib on experimental colon carcinomas in rats by
      quantitative assessments of tumor microcirculation parameters with
      immunohistochemical validation. MATERIALS AND METHODS: Colon carcinoma xenografts
      (HT-29) implanted subcutaneously in female athymic rats (n = 15) were imaged at
      baseline and after a one-week treatment with regorafenib by dynamic contrast
      enhanced computed tomography (128-slice dual-source computed tomography). The
      therapy group (n = 7) received regorafenib daily (10 mg/kg bodyweight).
      Quantitative parameters of tumor microcirculation (plasma flow, mL/100 mL/min),
      endothelial permeability (PS, mL/100 mL/min), and tumor vascularity (plasma
      volume, %) were calculated using a 2-compartment uptake model. Dynamic contrast
      enhanced computed tomography parameters were validated with immunohistochemical
      assessments of tumor microvascular density (CD-31), tumor cell apoptosis (TUNEL),
      and proliferation (Ki-67). RESULTS: Regorafenib suppressed tumor vascularity
      (15.7+/-5.3 to 5.5+/-3.5%; p<0.05) and tumor perfusion (12.8+/-2.3 to 8.8+/-2.9
      mL/100 mL/min; p = 0.063). Significantly lower microvascular density was observed
      in the therapy group (CD-31; 48+/-10 vs. 113+/-25, p<0.05). In regorafenib
      treated tumors, significantly more apoptotic cells (TUNEL; 11844+/-2927 vs.
      5097+/-3463, p<0.05) were observed. Dynamic contrast-enhanced computed tomography
      tumor perfusion and tumor vascularity correlated significantly (p<0.05) with
      microvascular density (CD-31; r = 0.84 and 0.66) and inversely with apoptosis
      (TUNEL; r = -0.66 and -0.71). CONCLUSIONS: Regorafenib significantly suppressed
      tumor vascularity (plasma volume) quantified by dynamic contrast-enhanced
      computed tomography in experimental colon carcinomas in rats with good-to
      moderate correlations to an immunohistochemical gold standard. Tumor response
      biomarkers assessed by dynamic contrast-enhanced computed tomography may be a
      promising future approach to a more personalized and targeted cancer therapy.

PMID- 24098756
TI  - Correlation between levels of 2, 5-hexanedione and pyrrole adducts in tissues of
      rats exposure to n-hexane for 5-days.
AB  - BACKGROUND: The formation of pyrrole adducts might be responsible for peripheral
      nerve injury caused by n-hexane. The internal dose of pyrrole adducts would
      supply more information for the neurotoxicity of n-hexane. The current study was
      designed to investigate the tissue distributions of 2, 5-hexanedione (2,5-HD) and
      pyrrole adducts in rats exposed to n-hexane, and analyze the correlation between
      pyrrole adducts and 2,5-HD in tissues. METHODS: Male Wistar rats were given daily
      dose of 500,1000, 2000, 4000 mg/kg bw n-hexane by gavage for 5 days. The rats
      were sacrificed 24 hours after the last administration. The levels of 2, 5
      hexanedione and pyrrole adducts in tissues were measured by gas chromatography
      and Ehrlich's reagent, respectively. The correlations between 2, 5-hexanedione
      and pyrrole adducts were analyzed by linear regression. RESULTS: Dose-dependent
      effects were observed between the dosage of n-hexane and 2, 5-hexanedione, and
      pyrrole adducts in tissues. The highest level of 2, 5-hexanedione was found in
      urine and the lowest in sciatic nerve, while the highest level of pyrrole adducts
      was seen in liver and the lowest in serum. There were significant correlations
      among the free 2, 5-hexanedione, total 2, 5-hexanedione and pyrrole adducts
      within the same tissues. Pyrrole adducts in serum showed the most significant
      correlation with free 2, 5-hexanedione or pyrrole adducts in tissues. CONCLUSION:
      The findings suggested that pyrrole adducts in serum might be a better indicator
      for the internal dose of free 2, 5-hexanedione and pyrrole adducts in tissues.

PMID- 24098757
TI  - Lower urinary tract symptoms (LUTS) as a risk factor for depressive symptoms in
      elderly men: results from a large prospective study in Southern Chinese men.
AB  - A cross-sectional relationship between lower urinary tract symptoms (LUTS) and
      depressive symptoms was previously reported among Southern Chinese men; however,
      the temporal relationship was unclear. Our objective is to evaluate the temporal
      relationship between moderate to severe lower urinary tract symptoms and
      clinically significant depressive symptoms in elderly Chinese men aged 65 in a
      prospective manner. In a prospective cohort of 2,000 Chinese men aged 65 to 92
      years in Hong Kong, we studied the association of having moderate to severe LUTS
      at baseline and having clinically relevant depressive symptoms at year 2 follow
      up. After excluding men with prostate or bladder cancer or surgery (n = 20) and
      lost to follow-up (n = 254), data on 1,726 subjects were analyzed. LUTS were
      measured by the International Prostate Symptom score; and clinically relevant
      depressive symptoms were measured by the Geriatric Depression Scale. The multiple
      logistic regressions showed that the presence of moderate-to-severe LUTS at
      baseline were significantly associated with increased risk for being depressed at
      two-year follow-up, with adjustments for demographic, lifestyle, medical factors,
      weight status and stressful life events (OR = 2.97; CI: 1.70-5.20). Association
      remained significant with additional adjustments for baseline GDS score (OR =
      1.88; CI: 1.03-3.41). LUTS are important risk factors in predicting the presence
      of clinically relevant depressive symptoms. In elderly men, increased awareness
      and possible screening are needed to detect the increased risk of clinically
      relevant depressive symptoms. 

PMID- 24098758
TI  - Edaravone protected human brain microvascular endothelial cells from
      methylglyoxal-induced injury by inhibiting AGEs/RAGE/oxidative stress.
AB  - Subjects with diabetes experience an increased risk of cerebrovascular disease
      and stroke compared with nondiabetic age-matched individuals. Increased formation
      of reactive physiological dicarbonyl compound methylglyoxal (MGO) seems to be
      implicated in the development of diabetic vascular complication due to its
      protein glycation and oxidative stress effect. Edaravone, a novel radical
      scavenger, has been reported to display the advantageous effects on ischemic
      stroke both in animals and clinical trials; however, little is known about
      whether edaravone has protective effects on diabetic cerebrovascular injury.
      Using cultured human brain microvascular endothelial cells (HBMEC), protective
      effects of edaravone on MGO and MGO enhancing oxygen-glucose deprivation (OGD)
      induced injury were investigated. Cell injury was measured by 3-(4,5
      Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) formation, cell
      account, lactate dehydrogenase (LDH) release and Rhodamine 123 staining. Advanced
      glycation end-products (AGEs) formation and receptor for advanced glycation end
      products (RAGE) expression were measured by western blotting. Cellular oxidative
      stress was measured by reactive oxygen species (ROS) release. Treatment of MGO
      for 24 h significantly induced HBMEC injury, which was inhibited by pretreatment
      of edaravone from 10-100 umol/l. What's more, treatment of MGO enhanced AGEs
      accumulation, RAGE expression and ROS release in the cultured HBMEC, which were
      inhibited by 100 umol/l edaravone. Finally, treatment of MGO for 24 h and then
      followed by 3 h OGD insult significantly enhanced cell injury when compared with
      OGD insult only, which was also protected by 100 umol/l edaravone. Thus,
      edaravone protected HBMEC from MGO and MGO enhancing OGD-induced injury by
      inhibiting AGEs/RAGE/oxidative stress. 

PMID- 24098759
TI  - Induction of senescence and identification of differentially expressed genes in
      tomato in response to monoterpene.
AB  - Monoterpenes, which are among the major components of plant essential oils, are
      known for their ecological roles as well for pharmaceutical properties. Geraniol,
      an acyclic monoterpene induces cell cycle arrest and apoptosis/senescence in
      various cancer cells and plants; however, the genes involved in the process and
      the underlying molecular mechanisms are not well understood. In this study, we
      demonstrate that treatment of tomato plants with geraniol results in induction of
      senescence due to a substantial alteration in transcriptome. We have identified
      several geraniol-responsive protein encoding genes in tomato using suppression
      subtractive hybridization (SSH) approach. These genes comprise of various
      components of signal transduction, cellular metabolism, reactive oxygen species
      (ROS), ethylene signalling, apoptosis and DNA damage response. Upregulation of
      NADPH oxidase and antioxidant genes, and increase in ROS level after geraniol
      treatment point towards the involvement of ROS in geraniol-mediated senescence.
      The delayed onset of seedling death and induced expression of geraniol-responsive
      genes in geraniol-treated ethylene receptor mutant (Nr) suggest that geraniol
      mediated senescence involves both ethylene dependent and independent pathways.
      Moreover, expression analysis during tomato ripening revealed that geraniol
      responsive genes are also associated with the natural organ senescence process. 

PMID- 24098760
TI  - An updated meta-analysis on the association of MDM2 SNP309 polymorphism with
      colorectal cancer risk.
AB  - BACKGROUND: The mouse double minute 2 (MDM2) gene encodes a phosphoprotein that
      interacts with P53 and negatively regulates its activity. The SNP309 polymorphism
      (T-G) in the promoter of MDM2 gene has been reported to be associated with
      enhanced MDM2 expression and tumor development. Studies investigating the
      association between MDM2 SNP309 polymorphism and colorectal cancer (CRC) risk
      reported conflicting results. We performed a meta-analysis of all available
      studies to explore the association of this polymorphism with CRC risk. METHODS:
      All studies published up to July 2013 on the association between MDM2 SNP309
      polymorphism and CRC risk were identified by searching electronic databases
      PubMed, EMBASE, and Chinese Biomedical Literature database (CBM) databases. The
      association between the MDM2 SNP309 polymorphism and CRC risk was assessed by
      odds ratios (ORs) together with their 95% confidence intervals (CIs). RESULTS: A
      total of 14 case-control studies including 4460 CRC cases and 4828 controls were
      identified. We did not find a significant association between the MDM2 SNP309
      polymorphism and CRC risk in all genetic models in overall population. However,
      in subgroup analysis by ethnicity, significant associations were found in Asians
      (TG vs. TT: OR = 1.197, 95% CI = 1.055-1.358, P=0.005; GG+TG vs. TT: OR = 1.246,
      95% CI = 1.106-1.404, P=0.000) and Africans. When stratified by HWE in controls,
      significantly increased risk was also found among the studies consistent with HWE
      (TG vs. TT: OR = 1.166, 95% CI = 1.037-1.311, P= 0.010). In subgroup analysis
      according to p53 mutation status, and gender, no any significant association was
      detected. CONCLUSIONS: The present meta-analysis suggests that the MDM2 is a
      candidate gene for CRC susceptibility. The MDM2 SNP309 polymorphism may be a risk
      factor for CRC in Asians.

PMID- 24098761
TI  - Combined inhibition of autophagy and caspases fails to prevent developmental
      nurse cell death in the Drosophila melanogaster ovary.
AB  - During the final stages of Drosophila melanogaster oogenesis fifteen nurse cells,
      sister cells to the oocyte, degenerate as part of normal development. This
      process involves at least two cell death mechanisms, caspase-dependent cell death
      and autophagy, as indicated by apoptosis and autophagy markers. In addition,
      mutations affecting either caspases or autophagy partially reduce nurse cell
      removal, leaving behind end-stage egg chambers with persisting nurse cell nuclei.
      To determine whether apoptosis and autophagy work in parallel to degrade and
      remove these cells as is the case with salivary glands during pupariation, we
      generated mutants doubly affecting caspases and autophagy. We found no
      significant increase in either the number of late stage egg chambers containing
      persisting nuclei or in the number of persisting nuclei per egg chamber in the
      double mutants compared to single mutants. These findings suggest that there is
      another cell death mechanism functioning in the ovary to remove all nurse cell
      remnants from late stage egg chambers. 

PMID- 24098763
TI  - Acroframosome-dependent KIFC1 facilitates acrosome formation during
      spermatogenesis in the caridean shrimp Exopalaemon modestus.
AB  - BACKGROUND: Acrosome formation and nuclear shaping are the main events in
      spermatogenesis. During spermiogenesis in Exopalaemon modestus, a unique
      microtubular structure called the acroframosome (AFS) forms in spermatids. The
      AFS links to a temporary organelle called the lamellar complex (LCx) leading to
      the formation of an everted umbrella-shaped acrosome and a dish-shaped nucleus in
      the mature sperm. These morphological changes require complex cell motility in
      which the C-terminal kinesin motor protein called KIFC1 is involved. In this
      study, we demonstrate that KIFC1 moves along the AFS and plays an important role
      in acrosome formation and nuclear shaping during spermatogenesis in E. modestus.
      METHODOLOGY/PRINCIPAL FINDINGS: We cloned a 3125 bp complete cDNA of kifc1 from
      the testis of E. modestus by PCR. The predicted secondary and tertiary structures
      of E. modestus KIFC1 contain three domains: a) the C-terminus, b) the stalk
      region, and the c) N-terminusl. Semi-quantitative RT-PCR detected the expression
      of kifc1 mRNA in different tissues of E. modestus. In situ hybridization
      demonstrated the temporal and spatial expression profile of kifc1 during
      spermiogenesis. Western blot identified the expression of KIFC1 in different
      tissues of E. modestus, including the testis. Immunofluorescence localized KIFC1,
      tubulin, GM130, and mitochondria in order to elucidate their role during
      spermiogenesis in E. modestus. CONCLUSION/SIGNIFICANCE: Our results indicate that
      KIFC1 transports the Golgi complex, mitochondria, and other cellular components
      that results in acrosome formation and nuclear shaping in E. modestus. The KIFC1
      transport function depends upon the microtubular structure called the
      acroframosome (AFS). This study describes some of the molecular mechanisms
      involved in the acrosome formation and nuclear shaping in E. modestus. In
      addition, this study may provide a model for studying the molecular mechanisms
      involved in spermatogenesis in other crustacean species and lead to a better
      understanding of the fertilization process in crustaceans.

PMID- 24098762
TI  - Extracellular acidic pH inhibits oligodendrocyte precursor viability, migration,
      and differentiation.
AB  - Axon remyelination in the central nervous system requires oligodendrocytes that
      produce myelin. Failure of this repair process is characteristic of
      neurodegeneration in demyelinating diseases such as multiple sclerosis, and it
      remains unclear how the lesion microenvironment contributes to decreased
      remyelination potential of oligodendrocytes. Here, we show that acidic
      extracellular pH, which is characteristic of demyelinating lesions, decreases the
      migration, proliferation, and survival of oligodendrocyte precursor cells (OPCs),
      and reduces their differentiation into oligodendrocytes. Further, OPCs exhibit
      directional migration along pH gradients toward acidic pH. These in vitro
      findings support a possible in vivo scenario whereby pH gradients attract OPCs
      toward acidic lesions, but resulting reduction in OPC survival and motility in
      acid decreases progress toward demyelinated axons and is further compounded by
      decreased differentiation into myelin-producing oligodendrocytes. As these
      processes are integral to OPC response to nerve demyelination, our results
      suggest that lesion acidity could contribute to decreased remyelination. 

PMID- 24098766
TI  - Effects of oscillatory flow on fertilization in the green sea urchin
      Strongylocentrotus droebachiensis.
AB  - Broadcast spawning invertebrates that live in shallow, high-energy coastal
      habitats are subjected to oscillatory water motion that creates unsteady flow
      fields above the surface of animals. The frequency of the oscillatory
      fluctuations is driven by the wave period, which will influence the stability of
      local flow structures and may affect fertilization processes. Using an
      oscillatory water tunnel, we quantified the percentage of eggs fertilized on or
      near spawning green sea urchins, Strongylocentrotus droebachiensis. Eggs were
      sampled in the water column, wake eddy, substratum and aboral surface under a
      range of different periods (T = 4.5-12.7 s) and velocities of oscillatory flow.
      The root-mean-square wave velocity (rms(u(w))) was a good predictor of
      fertilization in oscillatory flow, although the root-mean-square of total
      velocity (rms(u)), which incorporates all the components of flow (current, wave
      and turbulence), also provided significant predictions. The percentage of eggs
      fertilized varied between 50-85% at low flows (rms(u(w)) <0.02 m s(-1)),
      depending on the location sampled, but declined to below 10% for most locations
      at higher rms(u(w)). The water column was an important location for fertilization
      with a relative contribution greater than that of the aboral surface, especially
      at medium and high rms(u(w)) categories. We conclude that gametes can be
      successfully fertilized on or near the parent under a range of oscillatory flow
      conditions.

PMID- 24098764
TI  - Changes in first-line cART regimens and short-term clinical outcome between 1996
      and 2010 in The Netherlands.
AB  - OBJECTIVES: Document progress in HIV-treatment in The Netherlands since 1996 by
      reviewing changing patterns of cART use and relating those to trends in patients'
      short-term clinical outcomes between 1996 and 2010. DESIGN AND METHODS: 1996-2010
      data from 10,278 patients in the Dutch ATHENA national observational cohort were
      analysed. The annual number of patients starting a type of regimen was
      quantified. Trends in the following outcomes were described: i) recovery of 150
      CD4 cells/mm(3) within 12 months of starting cART; ii) achieving viral load (VL)
      suppression <=1,000 copies/ml within 12 months of starting cART; iii) switching
      from first-line to second-line regimen within three years of starting treatment;
      and iv) all-cause mortality rate per 100 person-years within three years of
      starting treatment. RESULTS: Between 1996 and 2010, first-line regimens changed
      from lamivudine/zidovudine-based or lamivudine/stavudine-based regimens with
      unboosted-PIs to tenofovir with either emtricitabine or lamivudine with NNRTIs.
      Mortality rates did not change significantly over time. VL suppression and CD4
      recovery improved over time, and the incidence of switching due to virological
      failure and toxicity more than halved between 1996 and 2010. These effects appear
      to be related to the use of new regimens rather than improvements in clinical
      care. CONCLUSION: The use of first-line cART in the Netherlands closely follows
      changes in guidelines, to the benefit of patients. While there was no significant
      improvement in mortality, newer drugs with better tolerability and simpler dosing
      resulted in improved immunological and virological recovery and reduced
      incidences of switching due to toxicity and virological failure.

PMID- 24098765
TI  - Recycling of kinesin-1 motors by diffusion after transport.
AB  - Kinesin motors drive the long-distance anterograde transport of cellular
      components along microtubule tracks. Kinesin-dependent transport plays a critical
      role in neurogenesis and neuronal function due to the large distance separating
      the soma and nerve terminal. The fate of kinesin motors after delivery of their
      cargoes is unknown but has been postulated to involve degradation at the nerve
      terminal, recycling via retrograde motors, and/or recycling via diffusion. We set
      out to test these models concerning the fate of kinesin-1 motors after completion
      of transport in neuronal cells. We find that kinesin-1 motors are neither
      degraded nor returned by retrograde motors. By combining mathematical modeling
      and experimental analysis, we propose a model in which the distribution and
      recycling of kinesin-1 motors fits a "loose bucket brigade" where individual
      motors alter between periods of active transport and free diffusion within
      neuronal processes. These results suggest that individual kinesin-1 motors are
      utilized for multiple rounds of transport. 

PMID- 24098767
TI  - The role of hydrogen peroxide and nitric oxide in the induction of plant-encoded
      RNA-dependent RNA polymerase 1 in the basal defense against Tobacco mosaic virus.
AB  - Plant RNA-dependent RNA Polymerase 1 (RDR1) is an important element of the RNA
      silencing pathway in the plant defense against viruses. RDR1 expression can be
      elicited by viral infection and salicylic acid (SA), but the mechanisms of
      signaling during this process remains undefined. The involvement of hydrogen
      peroxide (H2O2) and nitric oxide (NO) in RDR1 induction in the compatible
      interactions between Tobacco mosaic tobamovirus (TMV) and Nicotiana tabacum,
      Nicotiana benthamiana, and Arabidopsis thaliana was examined. TMV inoculation
      onto the lower leaves of N. tabacum induced the rapid accumulation of H2O2 and NO
      followed by the increased accumulation of RDR1 transcripts in the non-inoculated
      upper leaves. Pretreatment with exogenous H2O2 and NO on upper leaf led to
      increased RDR1 expression and systemic TMV resistance. Conversely,
      dimethylthiourea (an H2O2 scavenger) and 2-(4-carboxyphenyl)- 4,4,5,5
      tetramethylimidazoline-1-oxyl-3-oxide (an NO scavenger) partly blocked TMV- and
      SA-induced RDR1 expression and increased TMV susceptibility, whereas pretreatment
      with exogenous H2O2 and NO failed to diminish TMV infection in N. benthamiana
      plants with naturally occurring RDR1 loss-of-function. Furthermore, in N. tabacum
      and A. thaliana, TMV-induced H2O2 accumulation was NO-dependent, whereas NO
      generation was not affected by H2O2. These results suggest that, in response to
      TMV infection, H2O2 acts downstream of NO to mediate induction of RDR1, which
      plays a critical role in strengthening RNA silencing to restrict systemic viral
      infection. 

PMID- 24098768
TI  - Combined amplicon pyrosequencing assays reveal presence of the apicomplexan "type
      N" (cf. Gemmocystis cylindrus) and Chromera velia on the Great Barrier Reef,
      Australia.
AB  - BACKGROUND: The coral is predominantly composed of the metabolically dependent
      coral host and the photosynthetic dinoflagellate Symbiodinium sp. The system as a
      whole interacts with symbiotic eukaryotes, bacteria and viruses.
      Gemmocystiscylindrus (cf. "type-N" symbiont) belonging to the obligatory
      parasitic phylum Apicomplexa (Alveolata) is ubiquitous in the Caribbean coral,
      but its presence in the Great Barrier Reef coral has yet to be documented.
      Approaches allowing identification of the healthy community from the pathogenic
      or saprobic organisms are needed for sustainable coral reef monitoring. METHODS &
      PRINCIPAL FINDINGS: We investigated the diversity of eukaryotes associated with a
      common reef-building corals from the southern Great Barrier Reef. We used three
      tag encoded 454 amplicon pyrosequencing assays targeting eukaryote small-subunit
      rRNA gene to demonstrate the presence of the apicomplexan type-N and a
      photosynthetic sister species to Apicomplexa-Chromeravelia. Amplicon
      pyrosequencing revealed presence of the small-subunit rRNA genes of known
      eukaryotic pathogens (Cryptosporidium and Cryptococcus). We therefore conducted
      bacterial tag encoded amplicon pyrosequencing assay for small-subunit rRNA gene
      to support effluent exposure of the coral. Bacteria of faecal origin
      (Enterobacteriales) formed 41% of total sequences in contrast to 0-2% of the
      coral-associated bacterial communities with and without C. velia, respectively.
      SIGNIFICANCE: This is the first time apicomplexan type-N has been detected in the
      Great Barrier Reef. Eukaryote tag encoded amplicon pyrosequencing assays
      demonstrate presence of apicomplexan type-N and C. Velia in total coral DNA. The
      data highlight the need for combined approaches for eukaryotic diversity studies
      coupled with bacterial community assessment to achieve a more realistic goals of
      defining the holobiont community and assessing coral disease. With increasing
      evidence of Apicomplexa in coral reef environments, it is important not only to
      understand the evolution of these organisms but also identify their potential as
      pathogens.

PMID- 24098769
TI  - Structural abnormalities in early Tourette syndrome children: a combined voxel
      based morphometry and tract-based spatial statistics study.
AB  - Tourette Syndrome (TS) is characterized with chronic motor and vocal tics
      beginning in childhood. Abnormality of both gray (GM) and white matter (WM) has
      been observed in cortico-striato-thalamo-cortical circuits and sensory-motor
      cortex of adult TS patient. It is not clear if these morphological changes are
      also present in TS children and if there are any microstructural changes of WM.
      To understand the developmental cause of such changes, we investigated volumetric
      changes of GM and WM using VBM and microstructural changes of WM using DTI, and
      correlated these changes with tic severity and duration. T1 images and Diffusion
      Tensor Images (DTI) from 21 TS children were compared with 20 age and gender
      matched health control children using a 1.5T Philips scanner. All of the 21 TS
      children met the DSM-IV-TR criteria. T1 images were analyzed using DARTEL-VBM in
      conjunction with statistical parametric mapping (SPM). Diffusion tensor imaging
      (DTI) analysis was performed using Tract-Based Spatial Statistics (TBSS). Brain
      volume changes were found in left superior temporal gyrus, left and right
      paracentral gyrus, right precuneous cortex, right pre- and post-central gyrus,
      left temporal occipital fusiform cortex, right frontal pole, and left lingual
      gyrus. Significant axial diffusivity (AD) and mean diffusivity (MD) increases
      were found in anterior thalamic radiation, right cingulum bundle projecting to
      the cingulate gurus and forceps minor. Decreases in white matter volume (WMV) in
      the right frontal pole were inversely related with tic severity (YGTSS), and
      increases in AD and MD were positively correlated with tic severity and duration,
      respectively. These changes in TS children can be interpreted as signs of neural
      plasticity in response to the experiential demand. Our findings may suggest that
      the morphological and microstructural measurements from structural MRI and DTI
      can potentially be used as a biomarker of the pathophysiologic pattern of early
      TS children.

PMID- 24098770
TI  - Comparison of three intervention models for promoting circumcision among migrant
      workers in western China to reduce local sexual transmission of HIV.
AB  - OBJECTIVE: Three models for promoting male circumcision (MC) as a preventative
      intervention against HIV infection were compared among migrant worker populations
      in western China. METHODS: A cohort study was performed after an initial cross
      sectional survey among migrant workers in three provincial level districts with
      high HIV prevalence in western China. A total of 1,670 HIV seronegative male
      migrants were cluster-randomized into three intervention models, in which the
      dissemination of promotional materials and expert- and volunteer-led discussions
      are conducted in one, two, and three stage interventions. Changes in knowledge of
      MC, acceptability of MC, MC surgery uptake, and the costs of implementation were
      analyzed at 6-month and 9-month follow-up visits. RESULTS: All three models
      significantly increased the participants' knowledge about MC. The three-stage
      model significantly increased the acceptability of MC among participants and led
      to greatest increase in MC uptake. At the end of follow-up, 9.2% (153/1,670) of
      participants underwent MC surgery; uptake among the one-, two-, and three-stage
      models were 4.9%, 9.3%, and 14.6%, respectively. Multivariable Cox regression
      analysis showed that three-stage model was the most effective method to scale up
      MC, with RR = 2.0 (95% CI, 1.3-3.1, P=0.002) compared to the on-site session
      model. The two-stage intervention model showed no significant difference with
      either the on-site session model (RR=1.5, 95% CI, 0.92-2.4, P=0.12) or three
      stage model (P=0.10). CONCLUSIONS: A three-stage intervention with gradual
      introduction of knowledge led to the significantly increase in MC uptake among
      migrant workers in western China, and was also the most cost-effective method
      among the three models.

PMID- 24098771
TI  - Amniotic fluid stem cells with low gamma-interferon response showed behavioral
      improvement in Parkinsonism rat model.
AB  - Amniotic fluid stem cells (AFSCs) are multipotent stem cells that may be used in
      transplantation medicine. In this study, AFSCs established from amniocentesis
      were characterized on the basis of surface marker expression and differentiation
      potential. To further investigate the properties of AFSCs for translational
      applications, we examined the cell surface expression of human leukocyte antigens
      (HLA) of these cells and estimated the therapeutic effect of AFSCs in
      parkinsonian rats. The expression profiles of HLA-II and transcription factors
      were compared between AFSCs and bone marrow-derived mesenchymal stem cells
      (BMMSCs) following treatment with gamma-IFN. We found that stimulation of AFSCs
      with gamma-IFN prompted only a slight increase in the expression of HLA-Ia and
      HLA-E, and the rare HLA-II expression could also be observed in most AFSCs
      samples. Consequently, the expression of CIITA and RFX5 was weakly induced by
      gamma-IFN stimulation of AFSCs compared to that of BMMSCs. In the transplantation
      test, Sprague Dawley rats with 6-hydroxydopamine lesioning of the substantia
      nigra were used as a parkinsonian-animal model. Following the negative gamma-IFN
      response AFSCs injection, apomorphine-induced rotation was reduced by 75% in
      AFSCs engrafted parkinsonian rats but was increased by 53% in the control group
      after 12-weeks post-transplantation. The implanted AFSCs were viable, and were
      able to migrate into the brain's circuitry and express specific proteins of
      dopamine neurons, such as tyrosine hydroxylase and dopamine transporter. In
      conclusion, the relative insensitivity AFSCs to gamma-IFN implies that AFSCs
      might have immune-tolerance in gamma-IFN inflammatory conditions. Furthermore,
      the effective improvement of AFSCs transplantation for apomorphine-induced
      rotation paves the way for the clinical application in parkinsonian therapy. 

PMID- 24098772
TI  - Patient reported differences in dry eye disease between men and women: impact,
      management, and patient satisfaction.
AB  - PURPOSE: Dry eye disease affects women twice as often as men, but there is little
      information on whether dry eye treatments, treatment satisfaction, or the impact
      of dry eye disease on patients' lives and vision might differ by sex. DESIGN:
      Questionnaire survey of 4000 participants in the Women's Health Study and the
      Physicians' Health Studies I and II with a prior report of a diagnosis of DED.
      METHODS: Among participants who re-confirmed a diagnosis of dry eye disease, we
      assessed symptoms, treatments, patient satisfaction and impact of dry eye
      disease, and analyzed differences between men and women using regression models.
      RESULTS: The final study population consisted of 1,518 women (mean age 70.7
      years) and 581 men (mean age 76.7 years), with a mean reported duration of dry
      eye disease of 10.5 years and 10.1 years, respectively. The frequency and
      severity of dry eye disease symptoms were higher among women (each P<0.0001), and
      women reported a greater impact on everyday activities (P<0.0001). Women were
      more likely to use artificial tears (P<0.0001) use them more often (P<0.0001),
      and to use Restasis(r) (P<0.0001), omega-3 fatty acids (P=0.0006), and have
      punctal occlusion (P=0.005). Women spent more money per month on dry eye
      treatments (P<0.0001), but reported greater dissatisfaction with treatment side
      effects (P=0.001), and the amount of time before treatments started working
      (P=0.03). CONCLUSIONS: These data show that dry eye disease is generally
      experienced as being more severe among women, having a greater impact on their
      self-assessed well-being.

PMID- 24098773
TI  - High-infiltration of tumor-associated macrophages predicts unfavorable clinical
      outcome for node-negative breast cancer.
AB  - The tumor microenvironment is composed of tumor cells, fibroblasts, endothelial
      cells and infiltrating immune cells, which may inhibit or promote tumor growth
      and progression. The objectives of this retrospective study were to characterize
      the density of tumor-associated macrophages (TAMs) in breast cancer, and to
      correlate the density of TAMs with clinicopathological parameters. Paraffin
      embedded specimens and clinicopathological data, including up to 5 years follow
      up information, were obtained from 172 breast cancer patients.
      Immunohistochemical staining for CD68 (marker for macrophages) was performed and
      evaluated in a blinded fashion. We found that TAMs were significantly frequent in
      high histopathological grade breast cancer patients. Breast cancer patients with
      a high density of TAMs had significantly lower rates of disease-free survival and
      5-year overall survival than patients with low density of TAMs. Furthermore, high
      infiltration of TAMs indicated worse survival rate for patients with node
      negative breast cancer. In conclusion, the number of TAMs in the tumor stroma is
      an independent predictor of survival time for breast cancer patients. High
      infiltration of TAMs is a significant unfavorable prognostic factor for patients
      with invasive breast cancer and, as such, is a potentially useful prognostic
      marker for breast cancer. 

PMID- 24098774
TI  - Characterization and comparison of extended-spectrum beta-lactamase (ESBL)
      resistance genotypes and population structure of Escherichia coli isolated from
      Franklin's gulls (Leucophaeus pipixcan) and humans in Chile.
AB  - We investigated the general level of antibiotic resistance with further analysis
      of extended-spectrum beta-lactamase (ESBL) prevalence, as well as the population
      structure of E. coli in fecal flora of humans and Franklin's gulls (Leucophaeus
      pipixcan) in central parts of Chile. We found a surprisingly high carriage rate
      of ESBL-producing E. coli among the gulls 112/372 (30.1%) as compared to the
      human population 6/49 (12.2%.) Several of the E. coli sequence types (STs)
      identified in birds have previously been reported as Multi Drug Resistant (MDR)
      human pathogens including the ability to produce ESBLs. This means that not only
      commensal flora is shared between birds and humans but also STs with pathogenic
      potential. Given the migratory behavior of Franklin's gulls, they and other
      migratory species, may be a part of ESBL dissemination in the environment and
      over great geographic distances. Apart from keeping the antibiotic use low,
      breaking the transmission chains between the environment and humans must be a
      priority to hinder the dissemination of resistance. 

PMID- 24098775
TI  - Prevalence of optic disc hemorrhages in rural central India. The Central Indian
      Eye and Medical Study.
AB  - PURPOSE: To determine the frequency of optic disc hemorrhages in a rural Indian
      population. METHODS: The population-based Central Indian Eye and Medical Study
      included 4711 subjects. Mean age was 48.5+/-12.9 years (range: 30-100 years).
      Color optic disc photographs were examined. RESULTS: Optic disc photographs were
      available for 4570 (97.0%) subjects. Prevalence of disc hemorrhages was 17/8869
      (0.19%; 95%CI:0.10,0.28) per eye and 16/4570 (0.35+/-0.09%; 95%CI:0.18,0.52) per
      subject. Prevalence of disc hemorrhages increased from 0.05% (95%CI:0.00,0.13) in
      the age group of 30-39 years to 0.25% (95CI:0.00,0.49) in the age group of 60-69
      years and to 0.91% (95%CI:0.24,1.58) in the age group of 70+ years. After
      adjusting for older age, higher systolic blood pressure, diabetes mellitus,
      myopic refractive error, smaller neuroretinal rim area and thinner retinal nerve
      fiber layer, occurrence of disc hemorrhages was associated only with glaucomatous
      optic nerve damage (P<0.001; Odds ratio: 87; 95%CI:32,239). Eleven of the 17
      (65%; 95%CI:39,90) disc hemorrhages were found in glaucomatous eyes. Out of 193
      glaucomatous eyes, 11 eyes (5.7%; 95%CI:2.4,9.0) showed a disc hemorrhage. Out of
      the 8676 non-glaucomatous eyes, 6 eyes (0.07%; 95%CI:0.01,0.12) had an optic disc
      hemorrhage. CONCLUSIONS: Prevalence of disc hemorrhages (0.2% per eye; 0.4% per
      subject) in Indians aged 30+ years was strongly associated with glaucoma after
      adjustment for age, blood pressure and diabetes mellitus. A disc hemorrhage
      suggested glaucomatous optic nerve damage with a positive predictive value of
      65%. About 6% of glaucomatous eyes showed a disc hemorrhage at the time of
      clinical examination highlighting the importance of optic disc hemorrhages for
      the diagnosis of glaucoma.

PMID- 24098776
TI  - Bone marrow mesenchymal stem cells stimulate proliferation and neuronal
      differentiation of retinal progenitor cells.
AB  - During retina development, retinal progenitor cell (RPC) proliferation and
      differentiation are regulated by complex inter- and intracellular interactions.
      Bone marrow mesenchymal stem cells (BMSCs) are reported to express a variety of
      cytokines and neurotrophic factors, which have powerful trophic and protective
      functions for neural tissue-derived cells. Here, we show that the expanded RPC
      cultures treated with BMSC-derived conditioned medium (CM) which was
      substantially enriched for bFGF and CNTF, expressed clearly increased levels of
      nuclear receptor TLX, an essential regulator of neural stem cell (NSC) self
      renewal, as well as betacellulin (BTC), an EGF-like protein described as
      supporting NSC expansion. The BMSC CM- or bFGF-treated RPCs also displayed an
      obviously enhanced proliferation capability, while BMSC CM-derived bFGF knocked
      down by anti-bFGF, the effect of BMSC CM on enhancing RPC proliferation was
      partly reversed. Under differentiation conditions, treatment with BMSC CM or CNTF
      markedly favoured RPC differentiation towards retinal neurons, including Brn3a
      positive retinal ganglion cells (RGCs) and rhodopsin-positive photoreceptors, and
      clearly diminished retinal glial cell differentiation. These findings demonstrate
      that BMSCs supported RPC proliferation and neuronal differentiation which may be
      partly mediated by BMSC CM-derived bFGF and CNTF, reveal potential limitations of
      RPC culture systems, and suggest a means for optimizing RPC cell fate
      determination in vitro. 

PMID- 24098777
TI  - GARP is regulated by miRNAs and controls latent TGF-beta1 production by human
      regulatory T cells.
AB  - GARP is a transmembrane protein present on stimulated human regulatory T
      lymphocytes (Tregs), but not on other T lymphocytes (Th cells). It presents the
      latent form of TGF-beta1 on the Treg surface. We report here that GARP favors the
      cleavage of the pro-TGF-beta1 precursor and increases the amount of secreted
      latent TGF-beta1. Stimulated Tregs, which naturally express GARP, and Th cells
      transfected with GARP secrete a previously unknown form of latent TGF-beta1 that
      is disulfide-linked to GARP. These GARP/TGF-beta1 complexes are possibly shed
      from the T cell surface. Secretion of GARP/TGF-beta1 complexes was not observed
      with transfected 293 cells and may thus be restricted to the T cell lineage. We
      conclude that in stimulated human Tregs, GARP not only displays latent TGF-beta1
      at the cell surface, but also increases its secretion by forming soluble
      disulfide-linked complexes. Moreover, we identified six microRNAs (miRNAs) that
      are expressed at lower levels in Treg than in Th clones and that target a short
      region of the GARP 3' UTR. In transfected Th cells, the presence of this region
      decreased GARP levels, cleavage of pro-TGF-beta1, and secretion of latent TGF
      beta1. 

PMID- 24098778
TI  - Palaeontological evidence for the last temporal occurrence of the ancient western
      Amazonian river outflow into the Caribbean.
AB  - Fossil catfishes from fluvio-lacustrine facies of late Miocene Urumaco, early
      Pliocene Castilletes and late Pliocene San Gregorio formations provide evidence
      of a hydrographic connection in what is today desert regions of northern Colombia
      and Venezuela. New discoveries and reevaluation of existing materials leads to
      the recognition of two new records of the pimelodid Brachyplatystoma cf.
      vaillantii, and of three distinct doradid taxa: Doraops sp., Rhinodoras sp., and
      an unidentified third form. The presence of fossil goliath long-whiskered
      catfishes and thorny catfishes are indicative of the persistence of a fluvial
      drainage system inflow into the South Caribbean during the Pliocene/Pleistocene
      boundary, complementary to the previous western Amazonian hydrographic system
      described from the Middle Miocene Villavieja Formation in central Colombia and
      Late Miocene Urumaco Formation in northwestern Venezuela. The Pliocene
      Castilletes and San Gregorio formations potentially represent the last
      lithostratigraphic units related with an ancient western Amazonian fish fauna and
      that drainage system in the Caribbean. Alternatively, it may preserve faunas from
      a smaller, peripheral river basin that was cut off earlier from the Amazon
      Orinoco, today found in the Maracaibo basin and the Magdalena Rivers. 

PMID- 24098779
TI  - The correlation of hippocampal T2-mapping with neuropsychology test in patients
      with Alzheimer's disease.
AB  - OBJECTIVES: 1) To deduce T2, the inverse of the transverse relaxation rate (R2),
      in the hippocampus of healthy adults; 2) to investigate the brain iron deposition
      in Alzheimer's disease (AD) patients and age-matched healthy controls using T2
      values. METHODS: T2-weighted data from the bilateral-hippocampi of ten AD
      patients and sixty healthy controls were collected at six echo time points using
      multi-slice multi-echo turbo spin echo (MSME-TSE) imaging on a 3.0 T MR-scanner,
      followed by the neuropsychological testing. The correlations between T2-values
      and Mini-Mental State Examination (MMSE) scores were investigated on group-wise
      basis (covariates in the group-wise analyses: gender, age, side and healthy/AD).
      RESULTS: There were no significant differences in hippocampal T2-values on intra
      gender and inter-gender basis (P > 0.05). Hippocampal T2-values of both sides
      were similar (right: 85.2+/-2.4 milliseconds; left: 85.3+/-2.5 milliseconds). The
      bilateral hippocampal T2 values correlated moderately with age (right: r = -0.59;
      left: -0.58; P < 0.001). The AD-group had significantly lower T2-values in the
      hippocampus when compared to normal controls (P < 0.001) and such low T2-values
      had a strong positive correlation with the MMSE score (R (2) = 0.97; P < 0.05).
      CONCLUSION: Patients with AD showed significantly lower T2 values, which can be
      attributed to the increased iron depositions in the hippocampus. A positive
      correlation between T2-values and cognition scores suggests that quantitative T2
      can be used in the early diagnosis of AD and in the monitoring of the treatment
      response.

PMID- 24098780
TI  - Spatiotemporal dynamics and demographic profiles of imported Plasmodium
      falciparum and Plasmodium vivax infections in Ontario, Canada (1990-2009).
AB  - We examined malaria cases reported to Ontario's public health surveillance
      systems from 1990 through 2009 to determine how temporal scale (longitudinal,
      seasonal), spatial scale (provincial, health unit), and demography (gender, age)
      contribute to Plasmodium infection in Ontario travellers. Our retrospective study
      included 4,551 confirmed cases of imported malaria reported throughout Ontario,
      with additional analysis at the local health unit level (i.e., Ottawa, Peel, and
      Toronto). During the 20-year period, Plasmodium vivax accounted for 50.6% of all
      cases, P. falciparum (38.6%), Plasmodium sp. (6.0%), P. ovale (3.1%), and P.
      malariae (1.8%). During the first ten years of the study (1990-1999), P. vivax
      (64% of all cases) was the dominant agent, followed by P. falciparum (28%);
      however, during the second ten years (2000-2009) the situation reversed and P.
      falciparum (55%) dominated, followed by P. vivax (30%). The prevalence of P.
      falciparum and P. vivax cases varied spatially (e.g., P. falciparum more
      prevalent in Toronto, P. vivax more prevalent in Peel), temporally (e.g. P.
      falciparum incidence increased during the 20-year study), and demographically
      (e.g. preponderance of male cases). Infection rates per 100,000 international
      travellers were estimated: rates of infection were 2* higher in males compared to
      females; rates associated with travel to Africa were 37* higher compared to
      travel to Asia and 126* higher compared to travel to the Americas; rates of
      infection were 2.3-3.5* higher in June and July compared to October through
      March; and rates of infection were highest in those 65-69 years old. Where
      exposure country was reported, 71% of P. falciparum cases reported exposure in
      Ghana or Nigeria and 63% of P. vivax cases reported exposure in India. Our study
      provides insights toward improving pre-travel programs for Ontarians visiting
      malaria-endemic regions and underscores the changing epidemiology of imported
      malaria in the province. 

PMID- 24098781
TI  - Attenuation of chondrogenic transformation in vascular smooth muscle by dietary
      quercetin in the MGP-deficient mouse model.
AB  - RATIONALE: Cartilaginous metaplasia of vascular smooth muscle (VSM) is
      characteristic for arterial calcification in diabetes and uremia and in the
      background of genetic alterations in matrix Gla protein (MGP). A better
      understanding of the molecular details of this process is critical for the
      development of novel therapeutic approaches to VSM transformation and arterial
      calcification. OBJECTIVE: This study aimed to identify the effects of
      bioflavonoid quercetin on chondrogenic transformation and calcification of VSM in
      the MGP-null mouse model and upon TGF-beta3 stimulation in vitro, and to
      characterize the associated alterations in cell signaling. METHODS AND RESULTS:
      Molecular analysis revealed activation of beta-catenin signaling in cartilaginous
      metaplasia in Mgp-/- aortae in vivo and during chondrogenic transformation of
      VSMCs in vitro. Quercetin intercepted chondrogenic transformation of VSM and
      blocked activation of beta-catenin both in vivo and in vitro. Although dietary
      quercetin drastically attenuated calcifying cartilaginous metaplasia in Mgp-/-
      animals, approximately one-half of total vascular calcium mineral remained as
      depositions along elastic lamellae. CONCLUSION: Quercetin is potent in preventing
      VSM chondrogenic transformation caused by diverse stimuli. Combined with the
      demonstrated efficiency of dietary quercetin in preventing ectopic chondrogenesis
      in the MGP-null vasculature, these findings indicate a potentially broad
      therapeutic applicability of this safe for human consumption bioflavonoid in the
      therapy of cardiovascular conditions linked to cartilaginous metaplasia of VSM.
      Elastocalcinosis is a major component of MGP-null vascular disease and is
      controlled by a mechanism different from chondrogenic transformation of VSM and
      not sensitive to quercetin.

PMID- 24098782
TI  - Are interstitial cells of Cajal involved in mechanical stress-induced gene
      expression and impairment of smooth muscle contractility in bowel obstruction?
AB  - BACKGROUND AND AIMS: The network of interstitial cells of Cajal (ICC) is altered
      in obstructive bowel disorders (OBD). However, whether alteration in ICC network
      is a cause or consequence of OBD remains unknown. This study tested the
      hypothesis that mechanical dilation in obstruction disrupts the ICC network and
      that ICC do not mediate mechanotranscription of COX-2 and impairment of smooth
      muscle contractility in obstruction. METHODS: Medical-grade silicon bands were
      wrapped around the distal colon to induce partial obstruction in wild-type and
      ICC deficient (W/W(v)) mice. RESULTS: In wild-type mice, colon obstruction led to
      time-dependent alterations of the ICC network in the proximal colon segment.
      Although unaffected on days 1 and 3, the ICC density decreased markedly and the
      network was disrupted on day 7 of obstruction. COX-2 expression increased, and
      circular muscle contractility decreased significantly in the segment proximal to
      obstruction. In W/W(v) control mice, COX-2 mRNA level was 4.0 (+/-1.1)-fold
      higher (n=4) and circular muscle contractility was lower than in wild-type
      control mice. Obstruction further increased COX-2 mRNA level in W/W(v) mice to
      7.2 (+/-1.0)-fold vs. W/W(v) controls [28.8 (+/-4.1)-fold vs. wild-type controls]
      on day 3. Obstruction further suppressed smooth muscle contractility in W/W(v)
      mice. However, daily administration of COX-2 inhibitor NS-398 significantly
      improved muscle contractility in both W/W(v) sham and obstruction mice.
      CONCLUSIONS: Lumen dilation disrupts the ICC network. ICC deficiency has limited
      effect on stretch-induced expression of COX-2 and suppression of smooth muscle
      contractility in obstruction. Rather, stretch-induced COX-2 plays a critical role
      in motility dysfunction in partial colon obstruction.

PMID- 24098783
TI  - Hypoxia pathways and cellular stress activate pancreatic stellate cells:
      development of an organotypic culture model of thick slices of normal human
      pancreas.
AB  - Pancreatic stellate cells (PSC) are involved in fibrogenesis and oncogenesis by
      modulating the extracellular matrix. AIM: To evaluate the effect of cellular
      stress on PSC activation using a model of normal human pancreatic tissue slices
      culture preserving the microenvironment. METHODS: Thin sections (300 MUm) of
      normal human pancreas were cultured under hyperoxia (90% O2) during 72 hours.
      Viability and morphological analysis were performed at baseline, H24, H48 and
      H72. Cell differentiation (insulin, trypsin, CA9 and CK7), hypoxia (HIF1-alpha),
      apoptosis (caspase-3), proliferation (Ki67), TGF-beta expression and PSC
      activation (smooth muscle actin (SMA), nestin) were assessed using
      immunostaining, longitudinally. Control experiments were performed under normoxic
      conditions (21% O2). RESULTS: Thirty sections per specimen (n=10) were cultured.
      Hypoxia pathways were activated by the higher expression of HIF1-alpha at H48 and
      H72. Apoptosis was limited with only rare acinar cells expressing of the caspase
      3 at 48 and H72 (NS). Morphological analysis showed gradual appearance of
      acinoductal metaplasia, proven by CK7 expression and ductal phenotype of
      dedifferentiated acini. Transdifferentiation of PSC was shown by de novo SMA
      immunochemistry at H24 and H48. Expression of Ki67 index identified significant
      proliferation of activated PSC (double immunostaining Ki67-SMA) at H48 and H72
      (p=0.02). In vitro culture of normal human pancreas thin sections is feasible
      with optimized cell viability at 72 hours. This model of culture in hyperoxic
      conditions provides evidences that cellular stress may rapidly induce
      transactivation of PSC with ducto-acinar metaplasia.

PMID- 24098784
TI  - A constitutively active Galphai3 protein corrects the abnormal retinal pigment
      epithelium phenotype of Oa1-/- mice.
AB  - PURPOSE: Ocular Albinism type 1 (OA1) is a disease caused by mutations in the OA1
      gene and characterized by the presence of macromelanosomes in the retinal pigment
      epithelium (RPE) as well as abnormal crossing of the optic axons at the optic
      chiasm. We showed in our previous studies in mice that Oa1 activates specifically
      Galphai3 in its signaling pathway and thus, hypothesized that a constitutively
      active Galphai3 in the RPE of Oa1-/- mice might keep on the Oa1 signaling cascade
      and prevent the formation of macromelanosomes. To test this hypothesis, we have
      generated transgenic mice that carry the constitutively active Galphai3 (Q204L)
      protein in the RPE of Oa1-/- mice and are now reporting the effects that the
      transgene produced on the Oa1-/- RPE phenotype. METHODS: Transgenic mice carrying
      RPE-specific expression of the constitutively active Galphai3 (Q204L) were
      generated by injecting fertilized eggs of Oa1-/- females with a lentivirus
      containing the Galphai3 (Q204L) cDNA. PCR, Southern blots, Western blots and
      confocal microscopy were used to confirm the presence of the transgene in the RPE
      of positive transgenic mice. Morphometrical analyses were performed using
      electron microscopy to compare the size and number of melanosomes per RPE area in
      putative Oa1-/-, Galphai3 (Q204L) transgenic mice with those of wild-type NCrl
      and Oa1-/- mice. RESULTS: We found a correlation between the presence of the
      constitutively active Galphai3 (Q204L) transgene and the rescue of the normal
      phenotype of RPE melanosomes in Oa1-/-, Galphai3 (Q204L) mice. These mice have
      higher density of melanosomes per RPE area and a larger number of small
      melanosomes than Oa1-/- mice, and their RPE phenotype is similar to that of wild
      type mice. CONCLUSIONS: Our results show that a constitutively active Galphai3
      protein can by-pass the lack of Oa1 protein in Oa1-/- mice and consequently
      rescue the RPE melanosomal phenotype.

PMID- 24098785
TI  - Familial occurrence of systemic mast cell activation disease.
AB  - Systemic mast cell activation disease (MCAD) comprises disorders characterized by
      an enhanced release of mast cell mediators accompanied by accumulation of
      dysfunctional mast cells. Demonstration of familial clustering would be an
      important step towards defining the genetic contribution to the risk of systemic
      MCAD. The present study aimed to quantify familial aggregation for MCAD and to
      investigate the variability of clinical and molecular findings (e.g. somatic
      mutations in KIT) among affected family members in three selected pedigrees. Our
      data suggest that systemic MCAD pedigrees include more systemic MCAD cases than
      would be expected by chance, i.e., compared with the prevalence of MCAD in the
      general population. The prevalence of MCAD suspected by symptom self-report in
      first-degree relatives of patients with MCAD amounted to approximately 46%,
      compared to prevalence in the general German population of about 17% (p<0.0001).
      In three families with a high familial loading of MCAD, the subtype of MCAD and
      the severity of mediator-related symptoms varied between family members. In
      addition, genetic alterations detected in KIT were variable, and included
      mutations at position 816 of the amino acid sequence. In conclusion, our data
      provide evidence for common familial occurrence of MCAD. Our findings observed in
      the three pedigrees together with recent reports in the literature suggest that,
      in familial cases (i.e., in the majority of MCAD), mutated disease-related
      operator and/or regulator genes could be responsible for the development of
      somatic mutations in KIT and other proteins important for the regulation of mast
      cell activity. Accordingly, the immunohistochemically different subtypes of MCAD
      (i.e. mast cell activation syndrome and systemic mastocytosis) should be more
      accurately regarded as varying presentations of a common generic root process of
      mast cell dysfunction, than as distinct diseases. 

PMID- 24098786
TI  - Solubilization and stabilization of isolated photosystem I complex with
      lipopeptide detergents.
AB  - It is difficult to maintain a target membrane protein in a soluble and functional
      form in aqueous solution without biological membranes. Use of surfactants can
      improve solubility, but it remains challenging to identify adequate surfactants
      that can improve solubility without damaging their native structures and
      biological functions. Here we report the use of a new class of lipopeptides to
      solubilize photosystem I (PS-I), a well known membrane protein complex. Changes
      in the molecular structure of these surfactants affected their amphiphilicity and
      the goal of this work was to exploit a delicate balance between detergency and
      biomimetic performance in PS-I solubilization via their binding capacity.
      Meanwhile, the effects of these surfactants on the thermal and structural
      stability and functionality of PS-I in aqueous solution were investigated by
      circular dichroism, fluorescence spectroscopy, SDS-PAGE analysis and O2 uptake
      measurements, respectively. Our studies showed that the solubility of PS-I
      depended on both the polarity and charge in the hydrophilic head of the
      lipopeptides and the length of its hydrophobic tail. The best performing
      lipopeptides in favour of PS-I solubility turned out to be C14DK and C16DK, which
      were comparable to the optimal amphiphilicity of the conventional chemical
      surfactants tested. Lipopeptides showed obvious advantages in enhancing PS-I
      thermostability over sugar surfactant DDM and some full peptide amphiphiles
      reported previously. Fluorescence spectroscopy along with SDS-PAGE analysis
      demonstrated that lipopeptides did not undermine the polypeptide composition and
      conformation of PS-I after solubilization; instead they showed better performance
      in improving the structural stability and integrity of this multi-subunit
      membrane protein than conventional detergents. Furthermore, O2 uptake
      measurements indicated that PS-I solubilized with lipopeptides maintained its
      functionality. The underlying mechanism for the favorable actions of lipopeptide
      in PS-I solubilization and stabilization is discussed. 

PMID- 24098787
TI  - Methylcobalamin facilitates collateral sprouting of donor axons and innervation
      of recipient muscle in end-to-side neurorrhaphy in rats.
AB  - Using ulnar nerve as donor and musculocutaneous nerve as recipient we found
      earlier that end-to-side neurorrhaphy resulted in weak functional reinnervation
      after lengthy survival. End-to-side neurorrhaphy however is the sole choice of
      nerve repair at times and has the advantage of conserving donor nerve function.
      Here, we investigated whether myelination-enhancing agent methylcobalamin and
      motoneuron trophic factor pleiotrophin enhances the recovery after end-to-side
      neurorrhaphy. Methylcobalamin significantly increased the expression of growth
      associated protein 43 and S100 protein and betaIII tubulin in musculocutaneous
      nerve 1 month after neurorrhaphy suggesting the ingrowth of ulnar axonal sprouts
      in reactive Schwann cell environment. Upper limb functional test, compound muscle
      action potential measurements, motor end plate counts, and axon and myelin
      analyses showed that methylcobalamin treatment alone or with pleiotrophin
      improved the recovery significantly, 3 and 6 months post-surgery. There were
      fewer axons, closer in number to that of the intact recipient nerve, found in the
      distal repaired nerve of the methylcobalamin-treated than that of the vehicle
      control, suggesting that methylcobalamin facilitates axonal maturation and
      eliminates supernumerary sprouts. In conclusion, our results showed that
      methylcobalamin does indeed enhance the recovery of peripheral nerve repaired in
      end-to-side configuration. 

PMID- 24098788
TI  - 2mit, an intronic gene of Drosophila melanogaster timeless2, is involved in
      behavioral plasticity.
AB  - BACKGROUND: Intronic genes represent ~6% of the total gene complement in
      Drosophila melanogaster and ~85% of them encode for proteins. We recently
      characterized the D. melanogaster timeless2 (tim2) gene, showing its active
      involvement in chromosomal stability and light synchronization of the adult
      circadian clock. The protein coding gene named 2mit maps on the 11(th) tim2
      intron in the opposite transcriptional orientation. METHODOLOGY/PRINCIPAL
      FINDINGS: Here we report the molecular and functional characterization of 2mit.
      The 2mit gene is expressed throughout Drosophila development, localizing mainly
      in the nervous system during embryogenesis and mostly in the mushroom bodies and
      ellipsoid body of the central complex in the adult brain. In silico analyses
      revealed that 2mit encodes a putative leucine-Rich Repeat transmembrane receptor
      with intrinsically disordered regions, harboring several fully conserved
      functional interaction motifs in the cytosolic side. Using insertional mutations,
      tissue-specific over-expression, and down-regulation approaches, it was found
      that 2mit is implicated in adult short-term memory, assessed by a courtship
      conditioning assay. In D. melanogaster, tim2 and 2mit do not seem to be
      functionally related. Bioinformatic analyses identified 2MIT orthologs in 21
      Drosophilidae, 4 Lepidoptera and in Apis mellifera. In addition, the tim2-2mit
      host-nested gene organization was shown to be present in A. mellifera and
      maintained among Drosophila species. Within the Drosophilidae 2mit-hosting tim2
      intron, in silico approaches detected a neuronal specific transcriptional binding
      site which might have contributed to preserve the specific host-nested gene
      association across Drosophila species. CONCLUSIONS/SIGNIFICANCE: Taken together,
      these results indicate that 2mit, a gene mainly expressed in the nervous system,
      has a role in the behavioral plasticity of the adult Drosophila. The presence of
      a putative 2mit regulatory enhancer within the 2mit-hosting tim2 intron could be
      considered an evolutionary constraint potentially involved in maintaining the
      tim2-2mit host-nested chromosomal architecture during the evolution of Drosophila
      species.

PMID- 24098789
TI  - Multi-scale spatial concatenations of local features in natural scenes and scene
      classification.
AB  - How does the visual system encode natural scenes? What are the basic structures
      of natural scenes? In current models of scene perception, there are two broad
      feature representations, global and local representations. Both representations
      are useful and have some successes; however, many observations on human scene
      perception seem to point to an intermediate-level representation. In this paper,
      we proposed natural scene structures, i.e., multi-scale spatial concatenations of
      local features, as an intermediate-level representation of natural scenes. To
      compile the natural scene structures, we first sampled a large number of multi
      scale circular scene patches in a hexagonal configuration. We then performed
      independent component analysis on the patches and classified the independent
      components into a set of clusters using the K-means method. Finally, we obtained
      a set of natural scene structures, each of which is characterized by a set of
      dominant clusters of independent components. We examined a range of statistics of
      the natural scene structures, compiled from two widely used datasets of natural
      scenes, and modeled their spatial arrangements at larger spatial scales using
      adjacency matrices. We found that the natural scene structures include a full
      range of concatenations of visual features in natural scenes, and can be used to
      encode spatial information at various scales. We then selected a set of natural
      scene structures with high information, and used the occurring frequencies and
      the eigenvalues of the adjacency matrices to classify scenes in the datasets. We
      found that the performance of this model is comparable to or better than the
      state-of-the-art models on the two datasets. These results suggest that the
      natural scene structures are a useful intermediate-level representation of visual
      scenes for our understanding of natural scene perception. 

PMID- 24098790
TI  - Prevalence and associated factors of glaucoma in rural central India. The Central
      India Eye and Medical Study.
AB  - PURPOSE: To assess the prevalence of glaucoma in rural Central India. METHODS:
      The population-based Central India Eye and Medical Study is a population-based
      study performed in a rural region of Central India. The study included 4711
      subjects (aged 30+ years). A detailed ophthalmic and medical examination was
      performed. Glaucoma was defined by glaucomatous optic disc morphology, and in a
      second step, by the criteria of the International Society of Geographical and
      Epidemiological Ophthalmology (ISGEO). RESULTS: Optic disc photographs were
      available for 4570 (97.0%) subjects. Glaucoma was detected in 122 subjects (51
      unilateral) (2.67% (95%CI: 2.20, 3.14). Glaucoma prevalence for the age groups of
      30-39yrs, 40-49yrs, 50-59yrs, 60-69yrs, 70-79yrs, and 80+ years was 0.54% (95%CI:
      0.11, 0.98), 1.03% (95%CI: 0.49, 1.57), 1.40% (95%CI: 0.58, 2.23), 6.62% (95%CI:
      4.92, 8.31), 8.71% (95%CI: 5.55, 11.75), and 14.3% (95%CI: 4.13, 24.4),
      respectively. In multivariable analysis, glaucoma was associated with higher age
      (P<0.001), lower body mass index (P = 0.025), lower blood hemoglobin
      concentration (P = 0.03), higher intraocular pressure (P<0.001), disc hemorrhages
      (P<0.001), higher prevalence of myopic retinopathy (P<0.001), lower level of
      education (P = 0.03), longer axial length (P<0.001), thinner retinal nerve fiber
      layer (P<0.001), higher vertical cup/disc diameter ratio (P<0.001), and narrow
      anterior chamber angle (P = 0.02). Ratio of open-angle glaucoma to angle-closure
      glaucoma was 7.7:1 (1.93% (95%CI: 1.64, 2.22) to 0.24% (95%CI: 0.14, 0.34)).
      Using the ISGEO criteria, glaucoma prevalence was 2.8% (95%CI: 2.3, 3.3) with a
      less clear association with older age. CONCLUSIONS: Glaucoma prevalence in remote
      rural Central India is comparable to other regions. Associated factors were older
      age, lower body mass index, lower blood concentration of hemoglobin, lower level
      of education, higher intraocular pressure, disc hemorrhage, myopic retinopathy,
      and longer axial length. The ratio of open-angle glaucoma to angle-closure
      glaucoma was about 8:1.

PMID- 24098791
TI  - Resource availability and competition shape the evolution of survival and growth
      ability in a bacterial community.
AB  - Resource availability is one of the main factors determining the ecological
      dynamics of populations or species. Fluctuations in resource availability can
      increase or decrease the intensity of resource competition. Resource availability
      and competition can also cause evolutionary changes in life-history traits. We
      studied how community structure and resource fluctuations affect the evolution of
      fitness related traits using a two-species bacterial model system. Replicated
      populations of Serratia marcescens (copiotroph) and Novosphingobium capsulatum
      (oligotroph) were reared alone or together in environments with
      intergenerational, pulsed resource renewal. The comparison of ancestral and
      evolved bacterial clones with 1 or 13 weeks history in pulsed resource
      environment revealed species-specific changes in life-history traits. Co
      evolution with S. marcescens caused N. capsulatum clones to grow faster. The
      evolved S. marcescens clones had higher survival and slower growth rate then
      their ancestor. The survival increased in all treatments after one week, and
      thereafter continued to increase only in the S. marcescens monocultures that
      experienced large resource pulses. Though adaptive radiation is often reported in
      evolution studies with bacteria, clonal variation increased only in N. capsulatum
      growth rate. Our results suggest that S. marcescens adapted to the resource
      renewal cycle whereas N. capsulatum was more affected by the interspecific
      competition. Our results exemplify species-specific evolutionary response to both
      competition and environmental variation.

PMID- 24098792
TI  - The immuno-regulatory impact of orally-administered Hypericum perforatum extract
      on Balb/C mice inoculated with H1n1 influenza A virus.
AB  - Hypericumperforatum (H. perforatum) ethanol extract has been found to inhibit
      lipopolysaccharide-induced production of inflammatory mediators and cytokines in
      cultured macrophages. Therefore, it may be able to protect the host from
      excessive inflammation during viral infection. In the current study, the immune
      regulatory effect of H. perforatum extract was evaluated in A549 lung epithelial
      cells and BALB/c mice exposed to Influenza A/PR/8/34 H1N1 virus. In A549 cells,
      the extract (30 ug/mL) significantly inhibited influenza virus induced monocyte
      chemotactic protein (MCP)-1 and interferon-gamma induced protein 10 kD (IP-10),
      but dramatically increased interleukin-6 (IL-6). In mice inoculated intranasally
      with 10(7.9) EID50 of Influenza A/PR/8/34 H1N1 (high dose), daily oral treatment
      of H. perforatum extract at a rate of 110 mg/kg of body weight increased lung
      viral titer, bronchoalveolar lavage (BAL) pro-inflammatory cytokine and chemokine
      levels, and the infiltration of pro-inflammatory cells in the lung 5 days post
      inoculation, as compared to ethanol vehicle treated mice. Transcription of
      suppressor of cytokine signaling 3 (SOCS3) was increased by H. perforatum extract
      both in A549 cells and BALB/c mice, which could have interrupted anti-viral
      immune response and thus led to the inefficient viral clearance and increased
      lung inflammation. H. perforatum treatment resulted in minor reduction in viral
      titer without affecting body weight when mice were inoculated with a lower dose
      (~10(5.0) EID50) and H. perforatum was applied in the later phase of infection.
      Mice challenged intranasally with high dose of influenza virus (10(7.9) EID50)
      suffered from a higher mortality rate when dosed with H. perforatum extract. In
      conclusion, the current study showed that SOCS3 elevation by H. perforatum may
      cause impaired immune defense against influenza virus infection and lead to
      higher mortality. 

PMID- 24098793
TI  - Do biopesticides affect the demographic traits of a parasitoid wasp and its
      biocontrol services through sublethal effects?
AB  - Pesticide risk assessments are usually based on short-term acute toxicity tests,
      while longer-term population dynamic related traits, critical to the success of
      biological control and Integrated Pest Management (IPM) programs, are often
      overlooked. This is increasingly important with respect to new biopesticides that
      frequently cause no short-term acute effects, but that can induce multiple
      physiological and behavioral sublethal effects, leading to a decrease in
      population growth and ecosystem services. In this study we assessed the lethal
      and sublethal effects of six biopesticides [abamectin, azadirachtin, Bacillus
      thuringiensis, borax plus citrus oil (Prev-Am(r)), emamectin benzoate, and
      spinosad], used in tomato crops to control the invasive pest Tuta absoluta
      (Lepidoptera: Gelechiidae), on adults and pupae of the parasitoid Bracon
      nigricans (Hymenoptera: Braconidae). Data on female survival and production of
      female offspring were used to calculate population growth indexes as a measure of
      population recovery after pesticide exposure. Spinosad caused 100% and 80%
      mortality in exposed adults (even 10 d after the treatment) and pupae,
      respectively. Although most of the biopesticides had low levels of acute
      toxicity, multiple sublethal effects were observed. The biocontrol activity of
      both females that survived 1-h and 10-d old residues, and females that emerged
      from topically treated pupae was significantly affected by the application of the
      neurotoxic insecticides emamectin benzoate and abamectin. Furthermore, very low
      B. nigricans demographic growth indices were estimated for these two
      insecticides, indicating potential local extinction of the wasp populations.
      Among the tested products, Bt proved to be the safest for B. nigricans adults and
      pupae. Our findings emphasize that acute toxicity assessment alone cannot fully
      predict the actual impact of pesticides on non-target parasitoids. Thus,
      sublethal effects related to the species specific life-history variables must be
      carefully considered in order to assess pesticide risks and to incorporate new
      pesticides, including biopesticides, into IPM programmes. 

PMID- 24098794
TI  - What patient factors predict physicians' decision not to treat latent
      tuberculosis infection in tuberculosis contacts?
AB  - OBJECTIVE: The study aimed to determine factors that are associated with
      physicians' decision to offer treatment for latent tuberculosis infection (LTBI)
      in contacts of patients with tuberculosis. METHODS: We performed a nested case
      control study in a cohort of contacts of patients with pulmonary tuberculosis who
      had a tuberculin skin test (TST) >= 10 mm. Cases were those who were offered
      treatment for LTBI. Controls were randomly selected from those who were not
      offered treatment for LTBI by the reviewing physician. Odds ratios were estimated
      by multivariate logistic regression. RESULTS: There were 195 cases and 279
      controls. The following factors were significantly (positively or negatively)
      associated with being offered LTBI treatment in the multivariate analysis: female
      gender (OR 2.9; 95% CI 1.6-5.5), TST conversion (OR 3.9; 2.0-7.9), TST > 20 mm
      (OR 4.1; 1.8-9.1, for TST of 21-30 mm and OR 7.9; 2.6-23.8, for TST >30 mm),
      sputum smear positive index case (OR 12.7; 4.5-36.1), being overseas-born and
      immigration more than 2 years ago (OR 0.1; 0.06-0.3), being a health care worker
      (OR 0.2; 0.1-0.6), being a non-household contact of the TB index case (OR 0.3;
      0.2-0.6) and age >35 years (OR 0.2; 0.1-0.5 for age 35 to 54.9 years and OR 0.04;
      0.01-0.2 for age >=55 years). Previous BCG vaccine and chest x-ray findings were
      not significantly associated with physicians' decision to offer treatment for
      LTBI. CONCLUSIONS: Most factors that influenced physicians' decisions on
      treatment for LTBI were based on evidence of an association with risk of
      developing TB or risk of having an adverse reaction to treatment for LTBI.
      However, the decreased likelihood of offering treatment for LTBI to people born
      overseas, men and health care workers, was apparently not based on any evidence
      of risk. Efforts should be made to ensure that these groups are given access to
      treatment for LTBI.

PMID- 24098795
TI  - A community study of the psychological effects of the Omagh car bomb on adults.
AB  - BACKGROUND: The main aims of the study were to assess psychological morbidity
      among adults nine months after a car bomb explosion in the town of Omagh,
      Northern Ireland and to identify predictors of chronic posttraumatic stress
      disorder symptoms. METHOD: A questionnaire was sent to all adults in households
      in The Omagh District Council area. The questionnaire comprised established
      predictors of PTSD (such as pre-trauma personal characteristics, type of
      exposure, initial emotional response and long-term adverse physical or financial
      problems), predictors derived from the Ehlers and Clark (2000) cognitive model, a
      measure of PTSD symptoms and the General Health Questionnaire. RESULTS: Among
      respondents (n = 3131) the highest rates of PTSD symptoms and probable casesness
      (58.5%) were observed among people who were present in the street when the bomb
      exploded but elevated rates were also observed in people who subsequently
      attended the scene (21.8% probable caseness) and among people for whom someone
      close died (11.9%). People with a near miss (left the scene before the explosion)
      did not show elevated rates. Exposure to the bombing increased PTSD symptoms to a
      greater extent than general psychiatric symptoms. Previously established
      predictors accounted for 42% of the variance in PTSD symptoms among people
      directly exposed to the bombing. Predictors derived from the cognitive model
      accounted for 63%. CONCLUSIONS: High rates of chronic PTSD were observed in
      individuals exposed to the bombing. Psychological variables that are in principle
      amenable to treatment were the best predictors of PTSD symptoms. Teams planning
      treatment interventions for victims of future bombings and other traumas may wish
      to take these results into account.

PMID- 24098796
TI  - 31P MR spectroscopy and computational modeling identify a direct relation between
      Pi content of an alkaline compartment in resting muscle and phosphocreatine
      resynthesis kinetics in active muscle in humans.
AB  - The assessment of mitochondrial properties in skeletal muscle is important in
      clinical research, for instance in the study of diabetes. The gold standard to
      measure mitochondrial capacity non-invasively is the phosphocreatine (PCr)
      recovery rate after exercise, measured by (31)P Magnetic Resonance spectroscopy
      ((31)P MRS). Here, we sought to expand the evidence base for an alternative
      method to assess mitochondrial properties which uses (31)P MRS measurement of the
      Pi content of an alkaline compartment attributed to mitochondria (Pi2; as opposed
      to cytosolic Pi (Pi1)) in resting muscle at high magnetic field. Specifically,
      the PCr recovery rate in human quadriceps muscle was compared with the signal
      intensity of the Pi2 peak in subjects with varying mitochondrial content of the
      quadriceps muscle as a result of athletic training, and the results were entered
      into a mechanistic computational model of mitochondrial metabolism in muscle to
      test if the empirical relation between Pi2/Pi1 ratio and the PCr recovery was
      consistent with theory. Localized (31)P spectra were obtained at 7T from resting
      vastus lateralis muscle to measure the intensity of the Pi2 peak. In the
      endurance trained athletes a Pi2/Pi1 ratio of 0.07 +/- 0.01 was found, compared
      to a significantly lower (p<0.05) Pi2/Pi1 ratio of 0.03 +/- 0.01 in the normally
      active group. Next, PCr recovery kinetics after in magnet bicycle exercise were
      measured at 1.5T. For the endurance trained athletes, a time constant tauPCr 12
      +/- 3 s was found, compared to 24 +/- 5s in normally active subjects. Without any
      parameter optimization the computational model prediction matched the
      experimental data well (r(2) of 0.75). Taken together, these results suggest that
      the Pi2 resonance in resting human skeletal muscle observed at 7T provides a
      quantitative MR-based functional measure of mitochondrial density.

PMID- 24098797
TI  - Exercise enhances hippocampal recovery following binge ethanol exposure.
AB  - Binge drinking damages the brain, and although a significant amount of recovery
      occurs with abstinence, there is a need for effective strategies to maximize
      neurorestoration. In contrast to binge drinking, exercise promotes brain health,
      so the present study assessed whether it could counteract ethanol-induced damage
      by augmenting natural self-repair processes following one or more binge
      exposures. Adult female rats were exposed to 0 (control), 1 or 2 binges, using an
      established 4-day model of binge-induced neurodegeneration. Half of the animals
      in each group remained sedentary, or had running wheel access beginning 7 days
      after the final binge, and were sacrificed 28 days later. To assess binge-induced
      hippocampal damage and exercise restoration, we quantified volume of the dentate
      gyrus and number of granule neurons. We found that a single binge exposure
      significantly decreased the volume of the dentate gyrus and number of granule
      neurons. A second binge did not exacerbate the damage. Exercise completely
      restored baseline volume and granule neuron numbers. To investigate a potential
      mechanism of this restoration, we administered IdU (a thymidine analog) in order
      to label cells generated after the first binge. Previous studies have shown that
      neurogenesis in the dentate gyrus is decreased by binge alcohol exposure, and
      that the hippocampus responds to this insult by increasing cell genesis during
      abstinence. We found increased IdU labeling in binge-exposed animals, and a
      further increase in binged animals that exercised. Our results indicate that
      exercise reverses long-lasting hippocampal damage by augmenting natural self
      repair processes. 

PMID- 24098798
TI  - The association between diabetes mellitus and nonarteritic anterior ischemic
      optic neuropathy: a systematic review and meta-analysis.
AB  - BACKGROUND: The association of diabetes mellitus (DM) with nonarteritic anterior
      ischemic optic neuropathy (NAION) has been inconclusive. PURPOSE: To determine
      whether DM is associated with an increased risk of NAION. METHODS: A
      comprehensive literature search was performed for published studies reporting
      both DM and NAION based on PubMed and EMBASE. After reviewing characteristics of
      all the included studies systematically, meta-analytical method was employed to
      calculate the pooled odds ratio (OR) and associated 95% confidence interval (CI)
      from random-effects models. Heterogeneity was assessed by Q-statistic test.
      Funnel Plot, Begg's and Egger's linear regression test were applied to evaluate
      publication bias. A sensitivity analysis and meta-regression analysis were also
      performed to assess the robustness of results. RESULTS: 2,096 participants from
      12 case-control studies were pooled for a meta-analysis. The result of meta
      analysis of these studies indicated that DM is associated with increased risk of
      NAION (pooled OR = 1.64, 95% CI = 1.17-2.30; P = 0.004). Sensitivity analysis
      indicated our findings are robust, and meta-regression analysis revealed no
      significant effect in terms of geographical area, gender, age of patients with
      NAION, the year of the publication, source of the controls, and sample size (all
      p>0.05). Evidence of publication bias was not observed in our study. CONCLUSION:
      Meta-analysis suggests that DM might be associated with increased risk of NAION.

PMID- 24098799
TI  - Panobinostat synergistically enhances the cytotoxic effects of cisplatin,
      doxorubicin or etoposide on high-risk neuroblastoma cells.
AB  - High-risk neuroblastoma remains a therapeutic challenge with a long-term survival
      rate of less than 40%. Therefore, new agents are urgently needed to overcome
      chemotherapy resistance so as to improve the treatment outcome of this deadly
      disease. Histone deacetylase (HDAC) inhibitors (HDACIs) represent a novel class
      of anticancer drugs. Recent studies demonstrated that HDACIs can down-regulate
      the CHK1 pathway by which cancer cells can develop resistance to conventional
      chemotherapy drugs. This prompted our hypothesis that combining HDACIs with DNA
      damaging chemotherapeutic drugs for treating neuroblastoma would result in
      enhanced anti-tumor activities of these drugs. Treatment of high-risk
      neuroblastoma cell lines with a novel pan-HDACI, panobinostat (LBH589), resulted
      in dose-dependent growth arrest and apoptosis in 4 high-risk neuroblastoma cell
      lines. Further, the combination of panobinostat with cisplatin, doxorubicin, or
      etoposide resulted in highly synergistic antitumor interactions in the high-risk
      neuroblastoma cell lines, independent of the sequence of drug administration.
      This was accompanied by cooperative induction of apoptosis. Furthermore,
      panobinostat treatment resulted in substantial down-regulation of CHK1 and its
      downstream pathway and abrogation of the G2 cell cycle checkpoint. Synergistic
      antitumor interactions were also observed when the DNA damaging agents were
      combined with a CHK1-specific inhibitor, LY2603618. Contrary to panobinostat
      treatment, LY2603618 treatments neither resulted in abrogation of the G2 cell
      cycle checkpoint nor enhanced cisplatin, doxorubicin, or etoposide-induced
      apoptosis in the high-risk neuroblastoma cells. Surprisingly, LY2603618
      treatments caused substantial down-regulation of total CDK1. Despite this
      discrepancy between panobinostat and LY2603618, our results indicate that
      suppression of the CHK1 pathway by panobinostat is at least partially responsible
      for the synergistic antitumor interactions between panobinostat and the DNA
      damaging agents in high-risk neuroblastoma cells. The results of this study
      provide a rationale for clinical evaluation of the combination of panobinostat
      and cisplatin, doxorubicin, or etoposide for treating children with high-risk
      neuroblastoma. 

PMID- 24098800
TI  - Construction and characterization of normalized cDNA libraries by 454
      pyrosequencing and estimation of DNA methylation levels in three distantly
      related termite species.
AB  - In termites, division of labor among castes, categories of individuals that
      perform specialized tasks, increases colony-level productivity and is the key to
      their ecological success. Although molecular studies on caste polymorphism have
      been performed in termites, we are far from a comprehensive understanding of the
      molecular basis of this phenomenon. To facilitate future molecular studies, we
      aimed to construct expressed sequence tag (EST) libraries covering wide ranges of
      gene repertoires in three representative termite species, Hodotermopsis
      sjostedti, Reticulitermes speratus and Nasutitermes takasagoensis. We generated
      normalized cDNA libraries from whole bodies, except for guts containing microbes,
      of almost all castes, sexes and developmental stages and sequenced them with the
      454 GS FLX titanium system. We obtained >1.2 million quality-filtered reads
      yielding >400 million bases for each of the three species. Isotigs, which are
      analogous to individual transcripts, and singletons were produced by assembling
      the reads and annotated using public databases. Genes related to juvenile
      hormone, which plays crucial roles in caste differentiation of termites, were
      identified from the EST libraries by BLAST search. To explore the potential for
      DNA methylation, which plays an important role in caste differentiation of
      honeybees, tBLASTn searches for DNA methyltransferases (dnmt1, dnmt2 and dnmt3)
      and methyl-CpG binding domain (mbd) were performed against the EST libraries. All
      four of these genes were found in the H. sjostedti library, while all except
      dnmt3 were found in R. speratus and N. takasagoensis. The ratio of the observed
      to the expected CpG content (CpG O/E), which is a proxy for DNA methylation
      level, was calculated for the coding sequences predicted from the isotigs and
      singletons. In all of the three species, the majority of coding sequences showed
      depletion of CpG O/E (less than 1), and the distributions of CpG O/E were
      bimodal, suggesting the presence of DNA methylation.

PMID- 24098801
TI  - Progranulin protects vascular endothelium against atherosclerotic inflammatory
      reaction via Akt/eNOS and nuclear factor-kappaB pathways.
AB  - OBJECTIVE: Atherosclerosis is considered a chronic inflammatory disease,
      initiated by activation and dysfunction of the endothelium. Recently, progranulin
      has been regarded as an important modulator of inflammatory processes; however,
      the role for prgranulin in regulating inflammation in vascular endothelial cells
      has not been described. METHOD AND RESULTS: Signaling pathways mediated by
      progranulin were analyzed in human umbilical vein endothelial cells (HUVECs)
      treated with progranulin. Progranulin significantly induced Akt and endothelial
      nitric oxide synthase (eNOS) phosphorylation in HUVECs, an effect that was
      blocked with Akt inhibitor. Furthermore, nitric oxide (NO) level, the end product
      of Akt/eNOS pathway, was significantly upregulated after progranulin treatment.
      Next, we showed that progranulin efficiently inhibited lipopolysaccharide (LPS)
      mediated pro-inflammatory signaling. LPS-induced phosphorylation of IkappaB and
      nuclear factor-kappaB (NF-kappaB) levels decreased after progranulin treatment.
      Also, progranulin blocked translocation of NF-kappaB from the cytosol to the
      nucleus. In addition, progranulin significantly reduced the expression of
      vascular cell adhesion molecule-1 (VCAM-1) and intercellular adhesion molecule-1
      (ICAM-1) by inhibiting binding of NF- kappaB to their promoter regions and
      blocked attachment of monocytes to HUVECs. Progranulin also significantly reduced
      the expression of tumor necrosis factor receptor-alpha (TNF-alpha) and monocyte
      chemo-attractant protein-1 (MCP-1), the crucial inflammatory molecules known to
      aggravate atherosclerosis. CONCLUSION: Progranulin efficiently inhibited LPS
      mediated pro-inflammatory signaling in endothelial cells through activation of
      the Akt/eNOS pathway and attenuation of the NF-kappaB pathway, suggesting its
      protective roles in vascular endothelium against inflammatory reaction underlying
      atherosclerosis.

PMID- 24098802
TI  - CRACC-CRACC interaction between Kupffer and NK cells contributes to poly I:C/D
      GalN induced hepatitis.
AB  - CD2-like receptor activating cytotoxic cells (CRACC) is known as a critical
      activating receptor of natural killer (NK) cells. We have previously reported
      that NK cells contribute to Poly I:C/D-galactosamine (D-GalN)-induced fulminant
      hepatitis. Since natural killer group 2, member D (NKG2D) is considered critical
      but not the only activating receptor for NK cells, we investigated the role of
      CRACC in this model. We found that CRACC was abundant on hepatic NK cells but
      with low expression levels on Kupffer cells under normal conditions. Expression
      of CRACC on NK cells and Kupffer cells was remarkably upregulated after poly I:C
      injection. Hepatic CRACC mRNA levels were also upregulated in Poly I:C/D-GalN
      treated mice, and correlated positively with the serum alanine aminotransferase
      (ALT) levels. CRACC expression on Kupffer cells was specifically silenced by nano
      particle encapsulated siRNA in vivo, which significantly reduced Poly I:C/D-GalN
      induced liver injury. In co-culture experiments, it was further verified that
      silencing CRACC expression or blockade of CRACC activation by mAb reduced the
      production of interferon (IFN)-gamma and tumor necrosis factor (TNF)-alpha.
      Collectively, our findings suggest that CRACC-CRACC interaction between NK cells
      and resident Kupffer cells contributes to Poly I:C/D-GalN-induced fulminant
      hepatitis. 

PMID- 24098803
TI  - "Conferring authorship": biobank stakeholders' experiences with publication
      credit in collaborative research.
AB  - BACKGROUND: Multi-collaborator research is increasingly becoming the norm in the
      field of biomedicine. With this trend comes the imperative to award recognition
      to all those who contribute to a study; however, there is a gap in the current
      "gold standard" in authorship guidelines with regards to the efforts of those who
      provide high quality biosamples and data, yet do not play a role in the
      intellectual development of the final publication. METHODS AND FINDINGS: We
      carried out interviews with 36 individuals working in, or with links to, biobanks
      in Switzerland, in order to understand how they interpret, apply and value
      authorship criteria in studies involving biosamples. The majority of respondents
      feel that authorship is an important motivating factor in working and publishing
      collaboratively. However, our findings suggest that in some cases, authorship
      guidelines are being ignored in favor of departmental standards which recognize
      "scientific work" as meriting authorship. CONCLUSIONS: Our results support the
      current calls in the literature for an alternative method of crediting
      biomaterial contributions, in order to ensure appropriate authorship inclusion
      and promote collaborative research involving biobanks.

PMID- 24098804
TI  - Serial plasma choline measurements after cardiac arrest in patients undergoing
      mild therapeutic hypothermia: a prospective observational pilot trial.
AB  - OBJECTIVE: Choline is related to phospholipid metabolism and is a marker for
      global ischaemia with a small reference range in healthy volunteers. The aim of
      our study was to characterize the early kinetics of plasma free choline in
      patients after cardiac arrest. Additionally, we investigated the potential of
      plasma free choline to predict neurological outcome. METHODS: Twenty patients
      admitted to our medical intensive care unit were included in this prospective,
      observational trial. All patients were enrolled between May 2010 and May 2011.
      They received post cardiac arrest treatment including mild therapeutic
      hypothermia which was initiated with a combination of cold fluid and a feedback
      surface cooling device according to current guidelines. Sixteen blood samples per
      patient were analysed for plasma free choline levels within the first week after
      resuscitation. Choline was detected by liquid chromatography-tandem mass
      spectrometry. RESULTS: Most patients showed elevated choline levels on admission
      (median 14.8 umol/L; interquartile range; IQR 9.9-20.1) which subsequently
      decreased. 48 hours after cardiac arrest choline levels in all patients reached
      subnormal levels at a median of 4.0 umol/L (IQR 3-4.9; p = 0.001). Subsequently,
      choline levels normalized within seven days. There was no significant difference
      in choline levels when groups were analyzed in relation to neurological outcome.
      CONCLUSIONS: Our data indicate a choline deficiency in the early postresucitation
      phase. This could potentially result in impaired cell membrane recovery. The
      detailed characterization of the early choline time course may aid in planning of
      choline supplementation trials. In a limited number of patients, choline was not
      promising as a biomarker for outcome prediction.

PMID- 24098805
TI  - MIP-2A is a novel target of an anilinoquinazoline derivative for inhibition of
      tumour cell proliferation.
AB  - We recently identified a novel anilinoquinazoline derivative, Q15, as a potent
      apoptosis inducer in a panel of human cancer cell lines and determined that Q15
      targets hCAP-G2, a subunit of condensin II complex, leading to abnormal cell
      division. However, whether the defect in normal cell division directly results in
      cell death remains unclear. Here, we used an mRNA display method on a
      microfluidic chip to search for other Q15-binding proteins. We identified an
      additional Q15-binding protein, MIP-2A (MBP-1 interacting protein-2A), which has
      been reported to interact with MBP-1, a repressor of the c-Myc promoter. Our
      results indicate that Q15 inhibits the interaction between MIP-2A and MBP-1 as
      well as the expression of c-Myc protein, thereby inducing cell death. This study
      suggests that the simultaneous targeting of hCAP-G2 and MIP-2A is a promising
      strategy for the development of antitumor drugs as a treatment for intractable
      tumours. 

PMID- 24098806
TI  - The uremic toxin indoxyl sulphate enhances macrophage response to LPS.
AB  - Indoxyl sulphate (IS) is a protein-bound uremic toxin that results from the
      metabolism of dietary tryptophan normally excreted by kidney through the proximal
      tubules. Thus the toxin accumulates in the blood of patients with impaired renal
      function such as in chronic kidney disease (CKD). High IS serum levels in
      patients with CKD suggest its involvement in CKD progression and in the onset of
      complications. Its presence in plasma is also a powerful predictor of overall and
      cardiovascular morbidity/mortality. IS is a well known nephrovascular toxin but
      very little is known regarding its effects on the immune system and in particular
      during inflammation. In this study we examined the effect of IS on macrophage
      activation in response to lipopolysaccharide from E. coli (LPS), a gram negative
      bacterial endotoxin associated with inflammation and septic shock. To simulate
      the uremic condition, J774A.1 macrophages were incubated with IS at
      concentrations observed in uremic patients (1000-62.5 uM) both alone and during
      LPS challenge. IS alone induced release of reactive oxygen species (ROS), through
      a mechanism involving pro- and anti-oxidant systems, and alteration in
      intracellular calcium homeostasis. When added to J774A.1 macrophages in presence
      of LPS, IS significantly increased the nitric oxide (NO) release, inducible
      nitric oxide synthase (iNOS) and cycloxygenase-2 (COX-2) expression. IS pre
      treatment was also associated with an increase in tumor necrosis factor-alpha
      (TNF-alpha) and interleukin-6 (IL-6) production by macrophages stimulated with
      LPS. Mechanistic studies revealed that IS increased LPS-induced NF-kB nuclear
      translocation, ROS release and altered calcium concentrations, mainly because of
      mitochondrial calcium overloading. Moreover also in primary mouse peritoneal
      macrophages IS enhances the inflammatory response to LPS increasing ROS, NO,
      iNOS, COX-2, TNF-alpha, IL-6 and NF-kB levels. This study provides evidences that
      IS stimulates macrophage function and enhances inflammatory reasponse associated
      with LPS, thus contributing to altered immune response dysfunctions observed in
      CKD. 

PMID- 24098807
TI  - Genome-wide analysis of the Dof transcription factor gene family reveals soybean
      specific duplicable and functional characteristics.
AB  - The Dof domain protein family is a classic plant-specific zinc-finger
      transcription factor family involved in a variety of biological processes. There
      is great diversity in the number of Dof genes in different plants. However, there
      are only very limited reports on the characterization of Dof transcription
      factors in soybean (Glycine max). In the present study, 78 putative Dof genes
      were identified from the whole-genome sequence of soybean. The predicted GmDof
      genes were non-randomly distributed within and across 19 out of 20 chromosomes
      and 97.4% (38 pairs) were preferentially retained duplicate paralogous genes
      located in duplicated regions of the genome. Soybean-specific segmental
      duplications contributed significantly to the expansion of the soybean Dof gene
      family. These Dof proteins were phylogenetically clustered into nine distinct
      subgroups among which the gene structure and motif compositions were considerably
      conserved. Comparative phylogenetic analysis of these Dof proteins revealed four
      major groups, similar to those reported for Arabidopsis and rice. Most of the
      GmDofs showed specific expression patterns based on RNA-seq data analyses. The
      expression patterns of some duplicate genes were partially redundant while others
      showed functional diversity, suggesting the occurrence of sub-functionalization
      during subsequent evolution. Comprehensive expression profile analysis also
      provided insights into the soybean-specific functional divergence among members
      of the Dof gene family. Cis-regulatory element analysis of these GmDof genes
      suggested diverse functions associated with different processes. Taken together,
      our results provide useful information for the functional characterization of
      soybean Dof genes by combining phylogenetic analysis with global gene-expression
      profiling. 

PMID- 24098808
TI  - Mechanisms involved in the beneficial effects of spironolactone after myocardial
      infarction.
AB  - INTRODUCTION: Our objective was to analyze the effect of spironolactone on
      cardiac remodeling after experimental myocardial infarction (MI), assessed by
      matricellular proteins levels, cardiac collagen amount and distribution,
      myocardial tissue metalloproteinase inhibitor-1 (TIMP-1) concentration, myocyte
      hypertrophy, left ventricular architecture, and in vitro and in vivo cardiac
      function. METHODS: Wistar rats were assigned to 4 groups: control group, in which
      animals were submitted to simulated surgery (SHAM group; n=9); group that
      received spironolactone and in which animals were submitted to simulated surgery
      (SHAM-S group, n=9); myocardial infarction group, in which animals were submitted
      to coronary artery ligation (MI group, n=15); and myocardial infarction group
      with spironolactone supplementation (MI-S group, n=15). The rats were observed
      for 3 months. RESULTS: The MI group had higher values of left cardiac chambers
      and mass index and lower relative wall thicknesses compared with the SHAM group.
      In addition, diastolic and systolic functions were worse in the MI groups.
      However, spironolactone did not influence any of these variables. The MI-S group
      had a lower myocardial hydroxyproline concentration and myocyte cross-sectional
      area compared with the MI group. Myocardial periostin and collagen type III were
      lower in the MI-S group compared with the MI-group. In addition, TIMP-1
      concentration in myocardium was higher in the MI-S group compared with the MI
      group. CONCLUSIONS: The predominant consequence of spironolactone supplementation
      after MI is related to reductions in collagens, with discrete attenuation of
      other remodeling variables. Importantly, this effect may be modulated by
      periostin and TIMP-1 levels.

PMID- 24098809
TI  - Portacaval shunt established in six dogs using magnetic compression technique.
AB  - BACKGROUND AND AIMS: Installing the transjugular intrahepatic portosystemic shunt
      for portal hypertension is relatively safe, but complications are still high. To
      explore a new method of portacaval shunt, the magnetic compression technique was
      introduced into the shunting procedure. METHODS: A portal-inferior vena cava
      shunt was performed on 6 male mongrel dogs by two hemocompatible Nd-Fe-B
      permanent magnets, parent and daughter. The parent magnet was applied to the
      inferior vena cava guided by a catheter through the femoral vein. The daughter
      magnet was moved to the anastomosis position on the portal vein with a balloon
      catheter through the splenic vein. After the daughter magnet reached the target
      position, the two magnets acted to compress the vessel wall and hold it in place.
      Five to 7 days later, under X-ray guidance, the magnets were detached from the
      vessel wall with a rosch-uchida transjugular liver access set. One month later,
      histological analysis and portal venography were performed. RESULTS: 5-7 days
      after the first surgery, a mild intimal hyperplasia in the portal vein and the
      inferior vena cava, and continuity of the vascular adventitia from the portal
      vein to the inferior vena cava as observed. During the second surgery, the
      contrast media could be observed flowing from the portal vein into the inferior
      vena cava. Portal venography revealed that the portosystemic shunt was still
      present one month after the second surgery. CONCLUSIONS: Magnamosis via a device
      of novel design was successfully used to establish a portacaval shunt in dogs.

PMID- 24098810
TI  - Efficient production of retroviruses using PLGA/bPEI-DNA nanoparticles and
      application for reprogramming somatic cells.
AB  - Reprogramming of somatic cells to pluripotent cells requires the introduction of
      factors driving fate switches. Viral delivery has been the most efficient method
      for generation of induced pluripotent stem cells. Transfection, which precedes
      virus production, is a commonly-used process for delivery of nucleic acids into
      cells. The aim of this study is to evaluate the efficiency of PLGA/ bPEI
      nanoparticles in transfection and virus production. Using a modified method of
      producing PLGA nanoparticles, PLGA/bPEI-DNA nanoparticles were examined for
      transfection efficiency and virus production yield in comparison with PLGA-DNA,
      bPEI-DNA nanoparticles or liposome-DNA complexes. After testing various ratios of
      PLGA, bPEI, and DNA, the ratio of 6:3:1 (PLGA:bPEI:DNA, w/w/w) was determined to
      be optimal, with acceptable cellular toxicity. PLGA/bPEI-DNA (6:3:1)
      nanoparticles showed superior transfection efficiency, especially in multiple
      gene transfection, and viral yield when compared with liposome-DNA complexes. The
      culture supernatants of HEK293FT cells transfected with PLGA/bPEI-DNA of viral
      constructs containing reprogramming factors (Oct4, Sox2, Klf4, or c-Myc)
      successfully and more efficiently generated induced pluripotent stem cell
      colonies from mouse embryonic fibroblasts. These results strongly suggest that
      PLGA/bPEI-DNA nanoparticles can provide significant advantages in studying the
      effect of multiple factor delivery such as in reprogramming or direct conversion
      of cell fate. 

PMID- 24098811
TI  - Genetic diversity and population structure of rice pathogen Ustilaginoidea virens
      in China.
AB  - Rice false smut caused by the fungal pathogen Ustilaginoidea virens is becoming a
      destructive disease throughout major rice-growing countries. Information about
      its genetic diversity and population structure is essential for rice breeding and
      efficient control of the disease. This study compared the genome sequences of two
      U. virens isolates. Three SNP-rich genomic regions were identified as molecular
      markers that could be used to analyze the genetic diversity and population
      structure of U. virens in China. A total of 56 multilocus sequence types
      (haplotypes) were identified out of 162 representative isolates from 15 provinces
      covering five major rice-growing areas in China. However, the phylogeny, based on
      sequences at individual SNP-rich regions, strongly conflicted with each other and
      there were significant genetic differences between different geographical
      populations. Gene flow between the different geographical populations and genetic
      differentiation within each geographical population were also detected. In
      addition, genetic recombination and genetic isolation resulting from geographic
      separation was also found.

PMID- 24098812
TI  - Reproducibility of post-amphetamine [11C]FLB 457 binding to cortical D2/3
      receptors.
AB  - In a recent positron emission tomography (PET) study, we demonstrated the ability
      to measure amphetamine-induced dopamine (DA) release in the human cortex with the
      relatively high affinity dopamine D2/3 radioligand [(11)C]FLB 457. Herein we
      report on reproducibility and reliability of [(11)C]FLB 457 binding potential
      relative to non-displaceable uptake (BP(ND)) following an acute amphetamine
      challenge. Ten healthy human subjects were studied twice with [(11)C]FLB 457
      following an acute amphetamine (oral, 0.5 mg kg(-1) dose) challenge on two
      separate days approximately one week apart. D2/3 receptor binding parameters were
      estimated using a two-tissue compartment kinetic analysis in the cortical regions
      of interest and cerebellum (reference region). The test-retest variability and
      intraclass correlation coefficient were assessed for distribution volume (V(T)),
      binding potential relative to plasma concentration (BP(P)), and BP(ND) of
      [(11)C]FLB 457. The test-retest variability of [(11)C]FLB 457 V(T), BP(P) and
      BP(ND) were <= 17%, 22% and 11% respectively. These results, which are consistent
      with the published test-retest variability for this ligand measured under
      baseline conditions demonstrate that the post-amphetamine [(11)C]FLB 457 BP(ND)
      is reproducible. These data further support the use [(11)C]FLB 457 and
      amphetamine to characterize cortical dopamine transmission in neuropsychiatric
      disorders.

PMID- 24098813
TI  - Fatty liver is associated with transcriptional downregulation of stearoyl-CoA
      desaturase and impaired protein dimerization.
AB  - AIMS AND METHODS: We evaluated the modulation of liver stearoyl-CoA desaturase-1
      (Scd1) by dietary factors and insulin resistance (IR) in two experimental models
      of high-fat diet (HFD)-induced nonalcoholic fatty liver disease (NAFLD). The
      first model included Sprague Dawley (SD) rats that developed NAFLD without IR,
      and the second one included a rat model of genetic IR and cardiovascular disease,
      the spontaneously hypertensive rats (SHR) and its normotensive, insulin-sensitive
      control Wistar-Kyoto (WKY). The adult rats were given standard chow diet (CD) or
      HFD for 10 weeks. In all the animals, we explored the hepatic Scd1
      transcriptional activity and protein levels. RESULTS: HFD-fed rats of both
      strains developed severe NAFLD. Liver abundance of Scd1 mRNA was significantly
      decreased in HFD-fed rats regardless of the strain; SD-CD: 235+/-195 vs. SD-HFD
      4.5+/-2.9, p<0.0004, and SHR-CD: 75.6+/-10.8 vs. SHR-HFD: 4.48+/-17.4, and WKY
      CD: 168.7+/-17.4 vs. WKY-HFD: 12.9+/-17.4, p<0.000001 (mean+/-SE, ANCOVA adjusted
      by HOMA). Analysis of liver Scd1 protein expression showed a particular pattern
      in the HFD groups, characterized by the presence of high levels of a monomeric
      protein band (32.2-36.6 Kda, p<0.003) and decreased levels of a dimeric protein
      band (61.9-66.1 Kda, p<0.02) regardless of the rat strain. Pharmacologic
      intervention with the peroxisome proliferator-activated receptor alpha agonist
      clofibrate reverted the liver phenotype and significantly modified the hepatic
      Scd1 transcriptional activity and protein expression. CONCLUSION: Diet-induced
      fatty liver is associated with the downregulation of hepatic Scd1 transcript and
      de-dimerization of the protein, and these changes were not much affected by the
      status of peripheral IR.

PMID- 24098814
TI  - The distribution and 'in vivo' phase variation status of haemoglobin receptors in
      invasive meningococcal serogroup B disease: genotypic and phenotypic analysis.
AB  - Two haemoglobin-binding proteins, HmbR and HpuAB, contribute to iron acquisition
      by Neisseria meningitidis. These receptors are subject to high frequency,
      reversible switches in gene expression--phase variation (PV)--due to mutations in
      homopolymeric (poly-G) repeats present in the open reading frame. The
      distribution and PV state of these receptors was assessed for a representative
      collection of isolates from invasive meningococcal disease patients of England,
      Wales and Northern Ireland. Most of the major clonal complexes had only the HmbR
      receptor whilst the recently expanding ST-275-centred cluster of the ST-269
      clonal complex had both receptors. At least one of the receptors was in an 'ON'
      configuration in 76.3% of the isolates, a finding that was largely consistent
      with phenotypic analyses. As PV status may change during isolation and culture of
      meningococci, a PCR-based protocol was utilised to confirm the expression status
      of the receptors within contemporaneously acquired clinical specimens
      (blood/cerebrospinal fluid) from the respective patients. The expression state
      was confirmed for all isolate/specimen pairs with <15 tract repeats indicating
      that the PV status of these receptors is stable during isolation. This study
      therefore establishes a protocol for determining in vivo PV status to aid in
      determining the contributions of phase variable genes to invasive meningococcal
      disease. Furthermore, the results of the study support a putative but non
      essential role of the meningococcal haemoglobin receptors as virulence factors
      whilst further highlighting their vaccine candidacy.

PMID- 24098815
TI  - Novel multiplex bead-based assay for detection of IDH1 and IDH2 mutations in
      myeloid malignancies.
AB  - Isocitrate dehydrogenase 1 and 2 (IDH) mutations are frequently found in various
      cancer types such as gliomas, chondrosarcomas and myeloid malignancies. Their
      molecular detection has recently gained wide recognition in the diagnosis and
      prognosis of these neoplasms. For that purpose various molecular approaches have
      been used but a universally accepted method is still lacking. In this study we
      aimed to develop a novel bead-based liquid assay using Locked nucleic acids (LNA)
      modified oligonucleotide probes for multiplexed detection of the most frequent
      IDH1 (p.R132C, p.R132G, p.R132H, p.R132L, p.R132S) and IDH2 (p.R140Q, p.R172K)
      mutations. The method includes four steps: 1) PCR amplification of the targeted
      fragments with biotinylated primers; 2) Direct hybridization to barcoded
      microbeads with specific LNA-modified oligonucleotide probes; 3) Incubation with
      phycoerythrin coupled streptavidin; 4) Acquisition of fluorescent intensities of
      each set of beads on a flow platform (LuminexCorp., USA). We tested the
      performance of the assay on both artificial plasmid constructs and on clinical
      samples from 114 patients with known or suspected myeloid malignancies. The
      method appeared to be superior to direct sequencing having a much higher
      sensitivity of 2.5% mutant alleles. Applying this method to patients' samples we
      identified a total of 9 mutations (one IDH1 p.R132C, seven IDH2 p.R140Q and one
      IDH2 p.R172K). In conclusion, this method could be successfully implemented in
      the diagnostic work-up for various tumors known to harbor IDH1/2 mutations (e.g.
      myeloid malignancies, gliomas, etc.). International initiatives are needed to
      validate the different existing methods for detection of IDH1/2 mutations in
      clinical settings. 

PMID- 24098816
TI  - Polychaete richness and abundance enhanced in anthropogenically modified
      estuaries despite high concentrations of toxic contaminants.
AB  - Ecological communities are increasingly exposed to multiple chemical and physical
      stressors, but distinguishing anthropogenic impacts from other environmental
      drivers remains challenging. Rarely are multiple stressors investigated in
      replicated studies over large spatial scales (>1000 kms) or supported with
      manipulations that are necessary to interpret ecological patterns. We measured
      the composition of sediment infaunal communities in relation to anthropogenic and
      natural stressors at multiple sites within seven estuaries. We observed increases
      in the richness and abundance of polychaete worms in heavily modified estuaries
      with severe metal contamination, but no changes in the diversity or abundance of
      other taxa. Estuaries in which toxic contaminants were elevated also showed
      evidence of organic enrichment. We hypothesised that the observed response of
      polychaetes was not a 'positive' response to toxic contamination or a reduction
      in biotic competition, but due to high levels of nutrients in heavily modified
      estuaries driving productivity in the water column and enriching the sediment
      over large spatial scales. We deployed defaunated field-collected sediments from
      the surveyed estuaries in a small scale experiment, but observed no effects of
      sediment characteristics (toxic or enriching). Furthermore, invertebrate
      recruitment instead reflected the low diversity and abundance observed during
      field surveys of this relatively 'pristine' estuary. This suggests that
      differences observed in the survey are not a direct consequence of sediment
      characteristics (even severe metal contamination) but are related to parameters
      that covary with estuary modification such as enhanced productivity from nutrient
      inputs and the diversity of the local species pool. This has implications for the
      interpretation of diversity measures in large-scale monitoring studies in which
      the observed patterns may be strongly influenced by many factors that covary with
      anthropogenic modification. 

PMID- 24098817
TI  - Genetic variation in the Staphylococcus aureus 8325 strain lineage revealed by
      whole-genome sequencing.
AB  - Staphylococcus aureus strains of the 8325 lineage, especially 8325-4 and
      derivatives lacking prophage, have been used extensively for decades of research.
      We report herein the results of our deep sequence analysis of strain 8325-4.
      Assignment of sequence variants compared with the reference strain 8325
      (NRS77/PS47) required correction of errors in the 8325 reference genome, and
      reassessment of variation previously attributed to chemical mutagenesis of the
      restriction-defective RN4220. Using an extensive strain pedigree analysis, we
      discovered that 8325-4 contains 16 single nucleotide polymorphisms (SNP) arising
      prior to the construction of RN4220. We identified 5 indels in 8325-4 compared
      with 8325. Three indels correspond to expected Phi11, 12, 13 excisions, one indel
      is explained by a sequence assembly artifact, and the final indel (Delta63bp) in
      the spa-sarS intergenic region is common to only a sub-lineage of 8325-4 strains
      including SH1000. This deletion was found to significantly decrease (75%) steady
      state sarS but not spa transcript levels in post-exponential phase. The sub
      lineage 8325-4 was also found to harbor 4 additional SNPs. We also found large
      sequence variation between 8325, 8325-4 and RN4220 in a cluster of repetitive
      hypothetical proteins (SA0282 homologs) near the Ess secretion cluster. The
      overall 8325-4 SNP set results in 17 alterations within coding sequences.
      Remarkably, we discovered that all tested strains of the 8325-4 lineage lack
      phenol soluble modulin alpha3 (PSMalpha3), a virulence determinant implicated in
      neutrophil chemotaxis, biofilm architecture and surface spreading. Collectively,
      our results clarify and define the 8325-4 pedigree and reveal clear evidence that
      mutations existing throughout all branches of this lineage, including the widely
      used RN6390 and SH1000 strains, could conceivably impact virulence regulation. 

PMID- 24098818
TI  - The characteristic of heat wave effects on coronary heart disease mortality in
      Beijing, China: a time series study.
AB  - BACKGROUND: There is limited evidence for the impacts of heat waves on coronary
      heart disease (CHD) mortality in Beijing, capital city of China. OBJECTIVES: We
      aimed to find a best heat wave definition for CHD mortality; and explore the
      characteristic of heat wave effects on CHD in Beijing, China. METHODS: We
      obtained daily data on weather and CHD mortality in Beijing for years 2000-2011.
      A quasi-Poisson regression model was used to assess the short-term impact of heat
      waves on CHD mortality in hot season (May-September), while controlling for
      relative humidity, day of the week, long-term trend and season. We compared 18
      heat wave definitions by combining heat wave thresholds (87.5(th), 90.0(th),
      92.5(th), 95(th), 97.5(th), and 99(th) percentile of daily mean temperature) with
      different duration days (>= 2 to >= 4 days), using Akaike information criterion
      for quasi-Poisson. We examined whether heat wave effects on CHD mortality were
      modified by heat wave duration and timing. RESULTS: Heat wave definition using
      97.5(th) percentile of daily mean temperature (30.5  degrees C) and duration >= 2
      days produced the best model fit. Based on this heat wave definition, we found
      that men and elderly were sensitive to the first heat waves of the season, while
      women and young were sensitive to the second heat waves. In general, the longer
      duration of heat waves increased the risks of CHD mortality more than shorter
      duration for elderly. The first two days of heat waves had the highest impact on
      CHD mortality. Women and elderly were at higher risks than men and young when
      exposed to heat waves, but the effect differences were not statistically
      significant. CONCLUSIONS: Heat waves had significant impact on CHD mortality.
      This finding may have implications for policy making towards protecting human
      health from heat waves.

PMID- 24098819
TI  - A systematic review on the epidemiological data of erythema nodosum leprosum, a
      type 2 leprosy reaction.
AB  - BACKGROUND: Erythema Nodosum Leprosum (ENL) is a humoral immunological response
      in leprosy that leads to inflammatory skin nodules which may result in nerve and
      organ damage, and may occur years after antibiotic treatment. Multiple episodes
      are frequent and suppression requires high doses of immunosuppressive drugs.
      Global occurrence is unknown. METHODOLOGY/PRINCIPAL FINDINGS: Systematic review
      of evidence on ENL incidence resulted in 65 papers, predominantly from India (24)
      and Brazil (9), and inclusive of four reviews. Average incidences are based on
      cumulative incidence and size of study populations (n>100). In field-based
      studies 653/54,737 (1.2%) of all leprosy cases, 194/4,279 (4.5%) of MB cases, and
      86/560 (15.4%) of LL cases develop ENL. Some studies found a range of 1-8 per 100
      person-years-at-risk (PYAR) amongst MB cases. Hospital samples indicate that
      2,393/17,513 (13.7%) of MB cases develop ENL. Regional differences could not be
      confirmed. Multiple ENL episodes occurred in 39 to 77% of ENL patients, with an
      average of 2.6. Some studies find a peak in ENL incidence in the first year of
      treatment, others during the second and third year after starting MDT. The main
      risk factor for ENL is a high bacteriological index. CONCLUSIONS/SIGNIFICANCE:
      Few studies reported on ENL as a primary outcome, and definitions of ENL differed
      between studies. Although, in this review averages are presented, accurate data
      on global and regional ENL incidence is lacking. Large prospective studies or
      accurate surveillance data would be required to clarify this. Health staff needs
      to be aware of late reactions, as new ENL may develop as late as five years after
      MDT completion, and recurrences up to 8 years afterwards.

PMID- 24098820
TI  - The incubation period of Buruli ulcer (Mycobacterium ulcerans infection).
AB  - INTRODUCTION: Buruli Ulcer (BU) is caused by the environmental microbe
      Mycobacterium ulcerans. Despite unclear transmission, contact with a BU endemic
      region is the key known risk factor. In Victoria, Australia, where endemic areas
      have been carefully mapped, we aimed to estimate the Incubation Period (IP) of BU
      by interviewing patients who reported defined periods of contact with an endemic
      area prior to BU diagnosis. METHOD: A retrospective review was undertaken of 408
      notifications of BU in Victoria from 2002 to 2012. Telephone interviews using a
      structured questionnaire and review of notification records were performed.
      Patients with a single visit exposure to a defined endemic area were included and
      the period from exposure to disease onset determined (IP). RESULTS: We identified
      111 of 408 notified patients (27%) who had a residential address outside a known
      endemic area, of whom 23 (6%) reported a single visit exposure within the
      previous 24 months. The median age of included patients was 30 years (range: 6 to
      73) and 65% were male. 61% had visited the Bellarine Peninsula, currently the
      most active endemic area. The median time from symptom onset to diagnosis was 71
      days (range: 34-204 days). The midpoint of the reported IP range was utilized to
      calculate a point estimate of the IP for each case. Subsequently, the mean IP for
      the cohort was calculated at 135 days (IQR: 109-160; CI 95%: 113.9-156),
      corresponding to 4.5 months or 19.2 weeks. The shortest IP recorded was 32 days
      and longest 264 days (Figure 1 & 2). IP did not vary for variables investigated.
      CONCLUSIONS: The estimated mean IP of BU in Victoria is 135 days (IQR: 109-160
      days), 4.5 months. The shortest recorded was IP 34 days and longest 264 days. A
      greater understanding of BU IP will aid clinical risk assessment and future
      research.

PMID- 24098821
TI  - Proteomic analysis of the excretory-secretory products from larval stages of
      Ascaris suum reveals high abundance of glycosyl hydrolases.
AB  - BACKGROUND: Ascaris lumbricoides and Ascaris suum are socioeconomically important
      and widespread parasites of humans and pigs, respectively. The excretory
      secretory (ES) molecules produced and presented at the parasite-host interface
      during the different phases of tissue invasion and migration are likely to play
      critical roles in the induction and development of protective immune and other
      host responses. METHODOLOGY/PRINCIPAL FINDINGS: The aim of this study was to
      identify the ES proteins of the different larval stages (L3-egg, L3-lung and L4)
      by LC-MS/MS. In total, 106 different proteins were identified, 20 in L3-egg, 45
      in L3-lung stage and 58 in L4. Although most of the proteins identified were
      stage-specific, 15 were identified in the ES products of at least two stages. Two
      proteins, i.e. a 14-3-3-like protein and a serpin-like protein, were present in
      the ES products from the three different larval stages investigated.
      Interestingly, a comparison of ES products from L4 with those of L3-egg and L3
      lung showed an abundance of metabolic enzymes, particularly glycosyl hydrolases.
      Further study indicated that most of these glycolytic enzymes were
      transcriptionally upregulated from L4 onwards, with a peak in the adult stage,
      particularly in intestinal tissue. This was also confirmed by enzymatic assays,
      showing the highest glycosidase activity in protein extracts from adult worms
      gut. CONCLUSIONS/SIGNIFICANCE: The present proteomic analysis provides important
      information on the host-parasite interaction and the biology of the migratory
      stages of A. suum. In particular, the high transcriptional upregulation of
      glycosyl hydrolases from the L4 stage onwards reveals that the degradation of
      complex carbohydrates forms an essential part of the energy metabolism of this
      parasite once it establishes in the small intestine.

PMID- 24098823
TI  - NLRP3 controls Trypanosoma cruzi infection through a caspase-1-dependent IL-1R
      independent NO production.
AB  - Trypanosoma cruzi (T. cruzi) is an intracellular protozoan parasite and the
      etiological agent of Chagas disease, a chronic infectious illness that affects
      millions of people worldwide. Although the role of TLR and Nod1 in the control of
      T. cruzi infection is well-established, the involvement of inflammasomes remains
      to be elucidated. Herein, we demonstrate for the first time that T. cruzi
      infection induces IL-1beta production in an NLRP3- and caspase-1-dependent
      manner. Cathepsin B appears to be required for NLRP3 activation in response to
      infection with T. cruzi, as pharmacological inhibition of cathepsin B abrogates
      IL-1beta secretion. NLRP3(-/-) and caspase1(-/-) mice exhibited high numbers of
      T. cruzi parasites, with a magnitude of peak parasitemia comparable to MyD88(-/-)
      and iNOS(-/-) mice (which are susceptible models for T. cruzi infection),
      indicating the involvement of NLRP3 inflammasome in the control of the acute
      phase of T. cruzi infection. Although the inflammatory cytokines IL-6 and IFN
      gamma were found in spleen cells from NLRP3(-/-) and caspase1(-/-) mice infected
      with T. cruzi, these mice exhibited severe defects in nitric oxide (NO)
      production and an impairment in macrophage-mediated parasite killing.
      Interestingly, neutralization of IL-1beta and IL-18, and IL-1R genetic deficiency
      demonstrate that these cytokines have a minor effect on NO secretion and the
      capacity of macrophages to control T. cruzi infection. In contrast, inhibition of
      caspase-1 with z-YVAD-fmk abrogated NO production by WT and MyD88(-/-)
      macrophages and rendered them as susceptible to T. cruzi infection as NLRP3(-/-)
      and caspase-1(-/-) macrophages. Taken together, our results demonstrate a role
      for the NLRP3 inflammasome in the control of T. cruzi infection and identify
      NLRP3-mediated, caspase-1-dependent and IL-1R-independent NO production as a
      novel effector mechanism for these innate receptors. 

PMID- 24098822
TI  - Pathogenomic inference of virulence-associated genes in Leptospira interrogans.
AB  - Leptospirosis is a globally important, neglected zoonotic infection caused by
      spirochetes of the genus Leptospira. Since genetic transformation remains
      technically limited for pathogenic Leptospira, a systems biology pathogenomic
      approach was used to infer leptospiral virulence genes by whole genome comparison
      of culture-attenuated Leptospira interrogans serovar Lai with its virulent,
      isogenic parent. Among the 11 pathogen-specific protein-coding genes in which non
      synonymous mutations were found, a putative soluble adenylate cyclase with host
      cell cAMP-elevating activity, and two members of a previously unstudied ~15
      member paralogous gene family of unknown function were identified. This gene
      family was also uniquely found in the alpha-proteobacteria Bartonella
      bacilliformis and Bartonella australis that are geographically restricted to the
      Andes and Australia, respectively. How the pathogenic Leptospira and these two
      Bartonella species came to share this expanded gene family remains an
      evolutionary mystery. In vivo expression analyses demonstrated up-regulation of
      10/11 Leptospira genes identified in the attenuation screen, and profound in
      vivo, tissue-specific up-regulation by members of the paralogous gene family,
      suggesting a direct role in virulence and host-pathogen interactions. The
      pathogenomic experimental design here is generalizable as a functional systems
      biology approach to studying bacterial pathogenesis and virulence and should
      encourage similar experimental studies of other pathogens. 

PMID- 24098825
TI  - Intracoronary Near-Infrared Spectroscopy (NIRS) Imaging for Detection of Lipid
      Content of Coronary Plaques: Current Experience and Future Perspectives.
AB  - Acute coronary syndromes are frequently caused by "vulnerable" coronary plaques
      with a lipid-rich core. In 1993 near-infrared spectroscopy (NIRS) was first used
      to detect the lipid (cholesterol) content of atherosclerotic plaques in an
      experimental animal study. NIRS was then carefully validated using human
      atherosclerotic plaques (ex vivo), and has subsequently been developed for
      intracoronary imaging in humans, for which now an FDA-approved catheter-based
      NIRS system is available. NIRS provides a "chemogram" of the coronary artery wall
      and is used to detect lipid-rich plaques. Using this technology, recent studies
      have shown that lipid-rich plaques are very frequent in the culprit lesion of
      patients with an acute coronary syndrome, and are also common in non-culprit
      coronary lesions in these patients as compared to patients with stable coronary
      disease. First studies are evaluating the impact of statin therapy on coronary
      NIRS-detected lipid cores. Intracoronary NIRS imaging represents a highly
      interesting method for coronary plaque characterization in humans and may become
      a valuable tool for the development of novel therapies aiming to impact on the
      biology of human coronary artery plaques, likely in combination with other
      intracoronary imaging techniques, such as optical coherence tomography.

PMID- 24098824
TI  - MicroRNA expression profile in human macrophages in response to Leishmania major
      infection.
AB  - BACKGROUND: Leishmania (L.) are intracellular protozoan parasites able to survive
      and replicate in the hostile phagolysosomal environment of infected macrophages.
      They cause leishmaniasis, a heterogeneous group of worldwide-distributed
      affections, representing a paradigm of neglected diseases that are mainly
      embedded in impoverished populations. To establish successful infection and
      ensure their own survival, Leishmania have developed sophisticated strategies to
      subvert the host macrophage responses. Despite a wealth of gained crucial
      information, these strategies still remain poorly understood. MicroRNAs (miRNAs),
      an evolutionarily conserved class of endogenous 22-nucleotide non-coding RNAs,
      are described to participate in the regulation of almost every cellular process
      investigated so far. They regulate the expression of target genes both at the
      levels of mRNA stability and translation; changes in their expression have a
      profound effect on their target transcripts. METHODOLOGY/PRINCIPAL FINDINGS: We
      report in this study a comprehensive analysis of miRNA expression profiles in L.
      major-infected human primary macrophages of three healthy donors assessed at
      different time-points post-infection (three to 24 h). We show that expression of
      64 out of 365 analyzed miRNAs was consistently deregulated upon infection with
      the same trends in all donors. Among these, several are known to be induced by
      TLR-dependent responses. GO enrichment analysis of experimentally validated miRNA
      targeted genes revealed that several pathways and molecular functions were
      disturbed upon parasite infection. Finally, following parasite infection, miR-210
      abundance was enhanced in HIF-1alpha-dependent manner, though it did not
      contribute to inhibiting anti-apoptotic pathways through pro-apoptotic caspase-3
      regulation. CONCLUSIONS/SIGNIFICANCE: Our data suggest that alteration in miRNA
      levels likely plays an important role in regulating macrophage functions
      following L. major infection. These results could contribute to better
      understanding of the dynamics of gene expression in host cells during
      leishmaniasis.

PMID- 24098826
TI  - Avascular necrosis of the femoral head in HIV positive patients-an assessment of
      risk factors and early response to surgical treatment.
AB  - 26 consecutive patients (37 hips) with avascular necrosis (AVN) of the femoral
      head treated surgically at our institution from 1999 to 2008 were reviewed. The
      aims of the study were to evaluate the risk factors associated with AVN in HIV
      positive and HIV negative individuals, and assess early response to total hip
      replacement (THR) surgery in HIV positive and negative patients. There were 15
      male and 11 female patients in total. The mean age for all patients was 47.1+/-
      8.0 years (range, 33 to 66 years). 12 patients were HIV positive, 11 patients
      were HIV negative and 3 patients had unknown HIV status. Excessive alcohol intake
      was the most common risk factor for developing AVN .15 patients (58%) had more
      than one risk factor for AVN and only 2/12 (17%) HIV positive patients had no
      other risk factor apart from HIV infection. There were no early postoperative
      complications in 34 arthroplasties in both HIV positive and negative patients.
      The aetiology of AVN seems often to be multifactorial, even in the presence of
      HIV infection. Early response to arthroplasty surgery in AVN of the femoral head
      is equally good irrespective of the HIV serostatus of the patients. 

PMID- 24098827
TI  - Acute confusion and ataxia in the emergency department with an unexpected
      underlying diagnosis.

PMID- 24098828
TI  - Womens experiences of HIV testing and counselling in the labour ward: a case of
      Bwaila hospital.
AB  - INTRODUCTION: HIV counseling and testing during labour can be emotional, but is
      important because it allows mothers and babies to receive PMTCT prophylaxis if
      previous identification of HIV infection has not occurred. The study explores how
      HIV testing and counseling during early labour affects women. METHODOLOGY: This
      was a qualitative exploratory study to understand women's experiences during
      early labor. From September to October 2009, we conducted 10 indepth interviews
      with women who tested for HIV during early labour. We recruited women who tested
      > 3 months previously and those who had never tested for HIV from the postpartum
      ward of Bwaila Hospital. Data were analyzed manually using the life story
      approach in order to examine and analyse subjective experiences of women and
      their constructions of the social world. Transcripts were read multiple times to
      understand meanings which participants attached to their experiences. We coded
      data according to emerging themes and subthemes. RESULTS: Ten women 20-35 years
      were interviewed. Eight women had unknown HIV status while two had known HIV
      results but re-tested to update their status. Four women were found HIV-positive
      while 6 were HIV-negative. The primary theme was that women appreciated and
      accepted HIV testing and counseling. Testing was accepted as a necessary step to
      protect the infant from HIV infection. Counseling was viewed as helpful for
      acceptance of HIV status. One key subtheme was that HIV positive women
      experienced disappointment about their HIV diagnosis, though this was outweighed
      by the knowledge that one could protect her infant. All women viewed the short
      time to complete the counseling and testing procedures as favourable. CONCLUSION:
      Labour testing is acceptable and should be promoted to enhance PMTCT services by
      identifying HIV positive women with unknown status. Counseling helps women to
      accept being found with HIV and seek appropriate services.

PMID- 24098829
TI  - Undergraduate physiotherapy education in Malawi--the views of students on
      disability.
AB  - BACKGROUND: The College of Medicine in Malawi offers an undergraduate
      physiotherapy programme which started in 2010. The programme aims at training
      competent physiotherapists who can address the needs of people with disabilities.
      Therefore it is important to ensure that the perceptions of physiotherapy
      students towards disability are appropriate. OBJECTIVES: The study explored the
      views of the first cohort of physiotherapy students (n=19) in the pre-medical
      class in the College of Medicine, University of Malawi, on disability. METHODS:
      An audit of the views of premedical physiotherapy students was carried out in
      2010 using the Q methodology. RESULTS: Two independent factors emerged which
      captured the views of 19 students on disability. Most of the views expressed
      suggest that the students empathised with people with disabilities. Participants
      perceived that people with disabilities can have a good quality of life like
      everyone else, and are as intelligent as people without disabilities. However,
      some participants also expressed some discomfort when around people with
      disabilities. CONCLUSION: While there was consensus on some positive views, the
      negative viewpoints have the potential to act as a barrier to the rehabilitation
      of people with disabilities. The curriculum should ensure that the positive views
      are reinforced throughout the training programme, while the negative viewpoints
      are reversed.

PMID- 24098830
TI  - Prevalence and correlates of hunger among primary and secondary school children
      in Malawi: results from the 2009 Global School-based Health Survey.
AB  - BACKGROUND: Education is important in improving economies and creating literate,
      self-reliant and healthy societies. However, hunger is a barrier to basic
      education in Malawi. Hunger is also associated with a number of health risk
      behaviours, such as bullying, suicide ideation and unhygienic behaviours that may
      jeopardize the future of children. There are, however, limited data on the
      prevalence and associated factors of hunger among school children in Malawi.
      METHODS: The study used data from the Malawi Global School-Based Health Survey
      conducted in 2009 to estimate the prevalence of self-reported hunger within the
      last 30 days among primary and secondary school age group. It also assessed the
      association between self-reported hunger and some selected list of independent
      variables using frequency distribution, chi-squared test and logistic regression.
      RESULTS: A total of 2359 students were available for analysis. The overall self
      reported prevalence of hunger within the last 30 days was 12.5% (18.9% (172) in
      the rural and 8.3% (115) in urban areas; and 11.9%(123) for male and 12.5(148)
      for female children). In the final analysis, geographical location, eating
      fruits, having been bullied, suicide ideation, and washing hands with soap were
      significantly associated with hunger. CONCLUSION: Hunger in both primary and
      secondary school children in Malawi is a major social problem. The design of
      school feeding programmes aimed to reduce hunger should incorporate the factors
      identified as associated with hunger.

PMID- 24098831
TI  - Adherence to hand hygiene protocol by clinicians and medical students at Queen
      Elizabeth Central Hospital, Blantyre-Malawi.
AB  - BACKGROUND: While communicable diseases are the leading causes of morbidity and
      mortality in Malawi, the contribution of nosocomial or hospital-acquired
      infections (HAIs) is unknown but could be substantial. The single most important
      method of preventing nosocomial infections is hand hygiene. We report a study
      which was conducted in 2011 to investigate adherence to hand hygiene protocols by
      clinicians and medical students working at Queen Elizabeth Central Hospital in
      Blantyre, Malawi. METHODS: There were two parts to the study: a single blinded
      arm in which participants were observed without their knowledge by trained
      nurses; and a second arm which included self-completion of questionnaire after
      participant consent was obtained. The 2009 World Health Organization hand hygiene
      technique and recommendations which were adopted by Queen Elizabeth Central
      Hospital were used to define an opportunity for hand washing and effectiveness of
      hand washing. Hand hygiene effectiveness was defined as adherence to at least 6
      out of 7 steps (80%) of the hand hygiene technique when using alcohol-based
      formulation or at least 8 out of 10 steps (80%) of the hand hygiene technique
      when using water and soap formulation before and after having direct contact with
      patients or their immediate surroundings. RESULTS: Clinicians were found to have
      disinfected their hands more than medical students (p<0.05) but effectiveness was
      similar and very low between the two groups (p=0.2). No association was also
      found between having a personal hand sanitizer and hand hygiene practice (p=0.3).
      Adherence to hand hygiene was found to be 23%. Most of the participants mentioned
      infection transmission prevention as a reason for disinfecting their hands. Other
      reasons mentioned included: a routine personal hand hygiene behaviour and
      discomfort if not washing hands. The top three reasons why they did not disinfect
      hands were forgetfulness, unavailability of sanitizers and negligence.
      CONCLUSION: Adherence to hand hygiene practice was found to be low, with
      forgetfulness and negligence being the major contributing factors. A hospital
      wide multifaceted program aiming at clinicians and students education, adoption
      of alcohol based hand rubs as a primary formulation, production of colored poster
      reminders and encouraging role modeling of junior practitioners by senior
      practitioners can help improve compliance to hand hygiene.

PMID- 24098832
TI  - Case report: Down-staging locally advanced head and neck cancer in an HIV
      infected patient in a limited resource setting.

PMID- 24098833
TI  - Tamara Chipasula talks to Thengo Kavinya on her career in science communication.

PMID- 24098834
TI  - Analysis on Malawi government initiatives in the fight against the HIV/AIDS
      pandemic: is Malawi winning the fight against the HIV/AIDS pandemic?

PMID- 24098836
TI  - Birth size and physical activity in a cohort of Indian children aged 6-10 years.
AB  - There is evidence of a reduction in children's physical activity in India in the
      last decade. Our objective was to assess whether size and body composition at
      birth are associated with physical activity in school-aged children. Children
      from a prospective observational cohort study born in Mysore, South India between
      1997 and 1998 (n = 663) had neonatal anthropometric measurements made within 72 h
      of delivery [weight, mid-upper arm circumference (MUAC), chest, abdomen and head
      circumference, crown-heel, crown-buttock and leg length, triceps and subscapular
      skinfolds]. At 6-10 years, children (n = 449) were asked to wear AM7164 or GT1M
      Actigraph accelerometers for 7 days. Body composition was measured within 6
      months of activity monitoring. Arm muscle area at birth and time of activity
      monitoring was calculated from MUAC and skinfold measurements. Activity outcome
      measures were: mean accelerometer counts per minute (cpm); counts per day and
      proportion of time spent in moderate and vigorous activity. The mean (S.D.)
      number of days with >=500 min of recorded accelerometer data was 7.0 (1.1).
      Linear regression models showed no significant associations between any of the
      neonatal anthropometric measures and the activity variables. Body fat percentage
      at 7.5 years was negatively associated with all activity variables (B = -4.69,
      CI: -7.31, -2.07 for mean cpm). In conclusion, this study showed no associations
      between body size and skinfold thickness at birth and objectively measured
      physical activity in childhood. 

PMID- 24098835
TI  - Charcot foot and ankle with osteomyelitis.
AB  - This paper presents a review of the current literature discussing topics of
      Charcot osteoarthropathy, osteomyelitis, diagnosing osteomyelitis, antibiotic
      management of osteomyelitis, and treatment strategies for management of Charcot
      osteoarthropathy with concurrent osteomyelitis. 

PMID- 24098837
TI  - A look through 'lens' cubic mitochondria.
AB  - Cell membranes may fold up into three-dimensional nanoperiodic cubic structures
      in biological systems. Similar geometries are well studied in other disciplines
      such as mathematics, physics and polymer chemistry. The fundamental function of
      cubic membranes in biological systems has not been uncovered yet; however, their
      appearance in specialized cell types indicates a role as structural templates or
      perhaps direct physical entities with specialized biophysical properties. The
      mitochondria located at the inner segment of the retinal cones of tree shrew
      (Tupaia glis and Tupaia belangeri) contain unique patterns of concentric cristae
      with a highly ordered membrane arrangement in three dimensions similar to the
      photonic nanostructures observed in butterfly wing scales. Using a direct
      template matching method, we show that the inner mitochondrial membrane folds
      into multi-layered (8 to 12 layers) gyroid cubic membrane arrangements in the
      photoreceptor cells. Three-dimensional simulation data demonstrate that such
      multi-layer gyroid membrane arrangements in the retinal cones of a tree shrew's
      eye can potentially function as: (i) multi-focal lens; (ii) angle-independent
      interference filters to block UV light; and (iii) a waveguide photonic crystal.
      These theoretical results highlight for the first time the significance of multi
      layer cubic membrane arrangements to achieve near-quasi-photonic crystal
      properties through the simple and reversible biological process of continuous
      membrane folding. 

PMID- 24098838
TI  - On the topology of chromatin fibres.
AB  - The ability of cells to pack, use and duplicate DNA remains one of the most
      fascinating questions in biology. To understand DNA organization and dynamics, it
      is important to consider the physical and topological constraints acting on it.
      In the eukaryotic cell nucleus, DNA is organized by proteins acting as spools on
      which DNA can be wrapped. These proteins can subsequently interact and form a
      structure called the chromatin fibre. Using a simple geometric model, we propose
      a general method for computing topological properties (twist, writhe and linking
      number) of the DNA embedded in those fibres. The relevance of the method is
      reviewed through the analysis of magnetic tweezers single molecule experiments
      that revealed unexpected properties of the chromatin fibre. Possible biological
      implications of these results are discussed. 

PMID- 24098839
TI  - Trading spaces: building three-dimensional nets from two-dimensional tilings.
AB  - We construct some examples of finite and infinite crystalline three-dimensional
      nets derived from symmetric reticulations of homogeneous two-dimensional spaces:
      elliptic (S (2)), Euclidean (E (2)) and hyperbolic (H (2)) space. Those
      reticulations are edges and vertices of simple spherical, planar and hyperbolic
      tilings. We show that various projections of the simplest symmetric tilings of
      those spaces into three-dimensional Euclidean space lead to topologically and
      geometrically complex patterns, including multiple interwoven nets and tangled
      nets that are otherwise difficult to generate ab initio in three dimensions. 

PMID- 24098840
TI  - About collagen, a tribute to Yves Bouligand.
AB  - Yves Bouligand's analysis of the organizations of biological materials in
      relation to those of liquid crystals enabled the development of the idea that
      physical forces exerting their actions under strong spatial constraints determine
      the structures and morphologies of these materials. The different levels of
      organization in collagen have preoccupied him for a long time. We present here
      our recent works in this domain that we were still discussing with him a few
      months before his death at the age of 76 on 21 January 2011. After recalling the
      hierarchical set of structures built by collagen molecules, we analyse them,
      exploiting the properties of the curved space of the hypersphere and of the
      algorithm of phyllotaxis. Those two geometrical concepts can be proposed as
      structural archetypes founding the polymorphism of this complex material of
      biological origin. 

PMID- 24098841
TI  - Hard spheres on the gyroid surface.
AB  - We find that 48/64 hard spheres per unit cell on the gyroid minimal surface are
      entropically self-organized. Striking evidence is obtained in terms of the
      acceptance ratio of Monte Carlo moves and order parameters. The regular
      tessellations of the spheres can be viewed as hyperbolic tilings on the Poincare
      disc with a negative Gaussian curvature, one of which is, equivalently, the
      arrangement of angels and devils in Escher's Circle Limit IV. 

PMID- 24098842
TI  - Triply periodic minimal and constant mean curvature surfaces.
AB  - We want to summarize some established results on periodic surfaces which are
      minimal or have constant mean curvature, along with some recent results. We will
      do this from a mathematical point of view with a general readership in mind. 

PMID- 24098843
TI  - Three-dimensional periodic complex structures in soft matter: investigation using
      scattering methods.
AB  - Three-dimensional periodic complex structures are encountered in various soft
      matter systems such as liquid crystals, block-copolymer phases and the related
      nano-structured materials. Here, we review several well-defined topologies: two
      dimensional hexagonal phase, three-dimensional packing of spheres, tetrahedral
      close packing (tcp) bi-continuous and tri-continuous cubic phases. We illustrate
      how small-angle X-ray scattering experiments help us to investigate these
      different structures and introduce the main available structural models based on
      both direct and inverse methods. 

PMID- 24098844
TI  - Kaleidoscopic tilings, networks and hierarchical structures in blends of 3
      miktoarm star terpolymers.
AB  - Dissipative particle dynamics simulations are used to explore blends of 3
      miktoarm star terpolymers. The investigated system is a 50/50 blend of ABC and
      ABD stars, which is investigated as a function of composition and at different
      symmetric segregation levels. The study shows that in analogy to pure ABC star
      melts cylindrical tiling patters form, but now in four-coloured variants. Also, a
      large part of the phase diagram is dominated by multi-coloured network structures
      showing hierarchical features. Most prominently, a novel alternating gyroid
      network structure with a hyperbolic lamellar interface is predicted to form.
      Here, the two gyroidal nets are composed of respectively C and D components, with
      the minority A and B components forming the lamellar-like curved structure on the
      dividing interface between the two nets. 

PMID- 24098845
TI  - Formation of impeller-like helical DNA-silica complexes by polyamines induced
      chiral packing.
AB  - The helicity of DNA and its long-range chiral packing are widespread phenomena;
      however, the packing mechanism remains poorly understood both in vivo and in
      vitro. Here, we report the extraordinary DNA chiral self-assembly by silica
      mineralization, together with circular dichroism measurements and electron
      microscopy studies on the structure and morphology of the products. Mg(2+) ion
      and diethylenetriamine were found to induce right- and left-handed chiral DNA
      packing with two-dimensional-square p4mm mesostructures, respectively, to give
      corresponding enantiomeric impeller-like helical DNA-silica complexes. Moreover,
      formation of macroscopic impeller-like helical architectures depends on the types
      of polyamines and co-structure-directing agents and pH values of reaction
      solution. It has been suggested that interaction strength between negatively
      charged DNA phosphate strands and positively charged counterions may be the key
      factor for the induction of DNA packing handedness. 

PMID- 24098846
TI  - Smectic pores and defect cores.
AB  - Riemann's minimal surfaces, a one-parameter family of minimal surfaces, describe
      a bicontinuous lamellar system with pores connecting alternating layers. We
      demonstrate explicitly that Riemann's minimal surfaces are composed of a
      nonlinear sum of two oppositely handed helicoids. 

PMID- 24098847
TI  - Tensorial Minkowski functionals of triply periodic minimal surfaces.
AB  - A fundamental understanding of the formation and properties of a complex spatial
      structure relies on robust quantitative tools to characterize morphology. A
      systematic approach to the characterization of average properties of anisotropic
      complex interfacial geometries is provided by integral geometry which furnishes a
      family of morphological descriptors known as tensorial Minkowski functionals.
      These functionals are curvature-weighted integrals of tensor products of position
      vectors and surface normal vectors over the interfacial surface. We here
      demonstrate their use by application to non-cubic triply periodic minimal surface
      model geometries, whose Weierstrass parametrizations allow for accurate numerical
      computation of the Minkowski tensors. 

PMID- 24098848
TI  - The role of curvature in silica mesoporous crystals.
AB  - Silica mesoporous crystals (SMCs) offer a unique opportunity to study micellar
      mesophases. Replication of non-equilibrium mesophases into porous silica
      structures allows the characterization of surfactant phases under a variety of
      chemical and physical perturbations, through methods not typically accessible to
      liquid crystal chemists. A poignant example is the use of electron microscopy and
      crystallography, as discussed herein, for the purpose of determining the
      fundamental role of amphiphile curvature, namely mean curvature and Gaussian
      curvature, which have been extensively studied in various fields such as polymer,
      liquid crystal, biological membrane, etc. The present work aims to highlight some
      current studies devoted to the interface curvature on SMCs, in which electron
      microscopy and electron crystallography (EC) are used to understand the geometry
      of silica wall surface in bicontinuous and cage-type mesostructures through the
      investigation of electrostatic potential maps. Additionally, we show that by
      altering the synthesis conditions during the preparation of SMCs, it is possible
      to isolate particles during micellar mesophase transformations in the cubic
      bicontinuous system, allowing us to view and study epitaxial relations under the
      specific synthesis conditions. By studying the relationship between mesoporous
      structure, interface curvature and micellar mesophases using electron microscopy
      and EC, we hope to bring new insights into the formation mechanism of these
      unique materials but also contribute a new way of understanding periodic liquid
      crystal systems. 

PMID- 24098849
TI  - Electromagnetic characterization of millimetre-scale replicas of the gyroid
      photonic crystal found in the butterfly Parides sesostris.
AB  - We have used three-dimensional stereolithography to synthetically replicate the
      gyroid photonic crystal (PC) structure that occurs naturally in the butterfly
      Parides sesostris. We have experimentally characterized the transmission response
      of this structure in the microwave regime at two azimuthal angles (phi) over a
      comprehensive range of polar angles (theta). We have modelled its electromagnetic
      response using the finite-element method (FEM) and found excellent agreement with
      experimental data. Both theory and experiment show a single relatively broad
      transmission minimum at normal incidence (theta = 0 degrees ) that comprises
      several narrow band resonances which separate into clearly identifiable stop
      bands at higher polar angles. We have identified the specific effective geometric
      planes within the crystal, and their associated periodicities that give rise to
      each of these stop-bands. Through extensive theoretical FEM modelling of the
      gyroid PC structure, using varying filling fractions of material and air, we have
      shown that a gyroid PC with material volume fraction of 40 per cent is
      appropriate for optimizing the reflected bandwidth at normal incidence (for a
      refractive index contrast of 1.56). This is the same gyroid PC material volume
      fraction used by the butterfly P. sesostris itself to produce its green
      structurally coloured appearance. This infers further optimization of this
      biological PC beyond that of its lattice constant alone. 

PMID- 24098850
TI  - Hierarchical self-assembly of chiral fibres from achiral particles.
AB  - We investigate, by molecular dynamics simulation, the behaviour of discotic
      particles in a solvent of Lennard-Jones spheres. When chromonic disc-sphere
      interactions are imposed on these systems, three regimes of self-assembly are
      observed. At moderate temperatures, numerous short threads of discs develop, but
      these threads remain isolated from one another. Quenching to low temperatures,
      alternatively, causes all of the discs to floc into a single extended aggregate
      which typically comprises several distinct sections and contains numerous packing
      defects. For a narrow temperature range between these regimes, however, defect
      free chiral fibres are found to freely self-assemble. The spontaneous chirality
      of these fibres results from frustration between the hexagonal packing and
      interdigitation of neighbouring threads, the pitch being set by the particle
      shape. This demonstration of aggregate-wide chirality emerging owing to packing
      alone is pertinent to many biological and synthetic hierarchically self
      assembling systems. 

PMID- 24098851
TI  - Reflections concerning triply-periodic minimal surfaces.
AB  - In recent decades, there has been an explosion in the number and variety of
      embedded triply-periodic minimal surfaces (TPMS) identified by mathematicians and
      materials scientists. Only the rare examples of low genus, however, are commonly
      invoked as shape templates in scientific applications. Exact analytic solutions
      are now known for many of the low genus examples. The more complex surfaces are
      readily defined with numerical tools such as Surface Evolver software or the
      Landau-Ginzburg model. Even though table-top versions of several TPMS have been
      placed within easy reach by rapid prototyping methods, the inherent complexity of
      many of these surfaces makes it challenging to grasp their structure. The problem
      of distinguishing TPMS, which is now acute because of the proliferation of
      examples, has been addressed by Lord & Mackay (Lord & Mackay 2003 Curr. Sci. 85,
      346-362). 

PMID- 24098852
TI  - Complex tiling patterns in liquid crystals.
AB  - In this account recent progress in enhancing the complexity of liquid crystal
      self-assembly is highlighted. The discussed superstructures are formed mainly by
      polyphilic T-shaped and X-shaped molecules composed of a rod-like core, tethered
      with glycerol units at both ends and flexible non-polar chain(s) in lateral
      position, but also related inverted molecular structures are considered. A series
      of honeycomb phases composed of polygonal cylinders ranging from triangular to
      hexagonal, followed by giant cylinder honeycombs is observed for ternary T-shaped
      polyphiles on increasing the size of the lateral chain(s). Increasing the chain
      size further leads to new modes of lamellar organization followed by three
      dimensional and two-dimensional structures incorporating branched and non
      branched axial rod-bundles. Grafting incompatible chains to opposite sides of the
      rod-like core leads to quaternary X-shaped polyphiles. These form liquid
      crystalline honeycombs where different cells are filled with different material.
      Projected on an Euclidian plane, all honeycomb phases can be described either by
      uniformly coloured Archimedean and Laves tiling patterns (T-shaped polyphiles) or
      as multi-colour tiling patterns (X-shaped polyphiles). It is shown that geometric
      frustration, combined with the tendency to segregate incompatible chains into
      different compartments and the need to find a periodic tiling pattern, leads to a
      significant increase in the complexity of soft self-assembly. Mixing of different
      chains greatly enhances the number of possible 'colours' and in this way,
      periodic structures comprising up to seven distinct compartments can be
      generated. Relations to biological self-assembly are discussed shortly. 

PMID- 24098853
TI  - Iridescence and spectral filtering of the gyroid-type photonic crystals in
      Parides sesostris wing scales.
AB  - The cover scales on the wing of the Emerald-patched Cattleheart butterfly,
      Parides sesostris, contain gyroid-type biological photonic crystals that brightly
      reflect green light. A pigment, which absorbs maximally at approximately 395 nm,
      is immersed predominantly throughout the elaborate upper lamina. This pigment
      acts as a long-pass filter shaping the reflectance spectrum of the underlying
      photonic crystals. The additional effect of the filtering is that the spatial
      distribution of the scale reflectance is approximately angle-independent, leading
      to a stable wing pattern contrast. The spectral tuning of the original
      reflectance is verified by photonic band structure modelling. 

PMID- 24098854
TI  - Nano-Structured Gelatin/Bioactive Glass Hybrid Scaffolds for the Enhancement of
      Odontogenic Differentiation of Human Dental Pulp Stem Cells.
AB  - Tooth decay is one of the most common chronic disorders throughout the world.
      Regenerating decayed dentin/pulp structure requires the design of novel
      scaffolding materials that mimic the architecture of natural dental extracellular
      matrix (ECM) and provide suitable environments for the attachment, proliferation,
      differentiation, and biomineralization of dental pulp stem cells (DPSCs). In this
      work, we developed an approach to prepare three-dimensional (3D) nano-fibrous
      gelatin/silica bioactive glass (NF-gelatin/SBG) hybrid scaffolds that mimic the
      nano-structured architecture and chemical composition of natural dental ECM. This
      approach involved the combination of a thermally induced phase separation, sol
      gel, and porogen leaching process, and synthesized hybrid scaffolds possessing
      natural ECM-like architecture, high porosity, well-defined pore size and
      interconnectivity, and improved mechanical strength. An in vitro cell culture
      study showed that human DPSCs had a significantly higher proliferation rate on NF
      gelatin/SBG scaffolds compared to NF-gelatin scaffolds under the same conditions.
      Furthermore, the integration of SBG into the hybrid scaffold significantly
      promoted the differentiation and biomineralization of the human DPSCs. The
      alkaline phosphatase (ALP) activity and expressions of marker genes for
      odontogenic differentiation (Col I, ALP, OCN, DSPP and DMP-1) were all
      significantly higher in the NF-gelatin/SBG than in the NF-gelatin group. Those
      results were further confirmed by hematoxylin and eosin (H&E) and von Kossa
      staining, as evidenced by greater ECM secretion and mineral deposition in the
      hybrid scaffold. In summary, the biomimetic NF-gelatin/SBG hybrid scaffolds
      provide an excellent environment for the growth and differentiation of human
      DPSCs and are promising candidates for dentin/pulp tissue regeneration.

PMID- 24098856
TI  - Controlled fermentation and preservation of UGBA -an indigenous Nigerian
      fermented food.
AB  - Studies were carried out to screen various microbial isolates of UGBA obtained
      from both traditionally fermented and laboratory samples for some technical
      properties required for the fermentation of the product. The technical properties
      screened for were; ability to produce enzymes (amylase, protease and lipase) and
      bacteriocin production. Possible starter cultures were selected from the screened
      isolates for controlled fermentation of the product. Preservation of the product
      by dehydration method was also investigated. Various dehydrating temperatures
      were studied and the most appropriate temperature regime was adopted. The shelf-
      life of the dehydrated product was also determined. Proximate composition and the
      amino acid profile of both fresh samples and the dehydrated ones were also
      carried out so as to ensure that there is no significant nutrient lost during the
      process of dehydration. Rehydration of the preserved product was also examined.
      The following groups of organisms were isolated; Bacillus species, Proteus
      species, Staphylococcus species, Micrococcus species and Pseudomonas species.
      Bacillus species exhibited the highest potential for the fermentation of the
      product based on the result of the technical properties screened for. Two
      isolates identified as Bacillus subtilis and Bacillus lichenformis were
      particularly outstanding and were therefore selected as possible starter
      cultures. Controlled fermentation of UGBA using the selected organisms singly and
      as mixed culture produced samples that were similar to the ones produced by the
      traditional method. However, fermentation period was reduced from 72 hr to 48 hr
      using the two isolates as mixed culture for the fermentation process. The most
      appropriate temperature regime for dehydrating the product was found to be 50
      degrees C. Proximate analysis and amino acid profile assay of the products show
      that there is no significant difference between the preserved product and fresh
      sample. Shelf- life studies of the samples showed that there is a significant
      difference between the preserved sample and the fresh one in terms of their
      keeping quality (6 months and 3 days respectively). The fresh sample lost its
      integrity (colour, taste, texture and aroma) after 72 hours while the preserved
      sample maintained its integrity even after six months of storage under room
      temperature. 

PMID- 24098855
TI  - Effect of oxidative stress on sympathetic and renal vascular responses to
      ischemic exercise.
AB  - Reactive oxygen species (ROS), produced acutely during skeletal muscle
      contraction, are known to stimulate group IV muscle afferents and accentuate the
      exercise pressor reflex (EPR) in rodents. The effect of ROS on the EPR in humans
      is unknown. We conducted a series of studies using ischemic fatiguing rhythmic
      handgrip to acutely increase ROS within skeletal muscle, ascorbic acid infusion
      to scavenge free radicals, and hyperoxia inhalation to further increase ROS
      production. We hypothesized that ascorbic acid would attenuate the EPR and that
      hyperoxia would accentuate the EPR. Ten young healthy subjects participated in
      two or three experimental trials on separate days. Beat-by-beat measurements of
      heart rate (HR), mean arterial pressure (MAP), muscle sympathetic nerve activity
      (MSNA), and renal vascular resistance index (RVRI) were measured and compared
      between treatments (saline and ascorbic acid; room air and hyperoxia). At
      fatigue, the reflex increases in MAP (31 +/- 3 versus 29 +/- 2 mmHg), HR (19 +/-
      3 versus 20 +/- 3 bpm), MSNA burst rate (21 +/- 4 versus 23 +/- 4 burst/min), and
      RVRI (39 +/- 12 versus 44 +/- 13%) were not different between saline and ascorbic
      acid. Relative to room air, hyperoxia did not augment the reflex increases in
      MAP, HR, MSNA, or RVRI in response to exercise. Muscle metaboreflex activation
      and time/volume control experiments similarly showed no treatment effects. While
      contrary to our initial hypotheses, these findings suggest that ROS do not play a
      significant role in the normal reflex adjustments to ischemic exercise in young
      healthy humans.

PMID- 24098857
TI  - Analysis of recycled poly (styrene-co-butadiene) sulfonation: a new approach in
      solid catalysts for biodiesel production.
AB  - The disposal of solid waste is a serious problem worldwide that is made worse in
      developing countries due to inadequate planning and unsustainable solid waste
      management. In Mexico, only 2% of total urban solid waste is recycled. One non
      recyclable material is poly (styrene-co-butadiene), which is commonly used in
      consumer products (like components of appliances and toys), in the automotive
      industry (in instrument panels) and in food services (e.g. hot and cold drinking
      cups and glasses). In this paper, a lab-scale strategy is proposed for recycling
      poly (styrene-co-butadiene) waste by sulfonation with fuming sulfuric acid. Tests
      of the sulfonation strategy were carried out at various reaction conditions. The
      results show that 75 degrees C and 2.5 h are the operating conditions that
      maximize the sulfonation level expressed as number of acid sites. The modified
      resin is tested as a heterogeneous catalyst in the first step (known as
      esterification) of biodiesel production from a mixture containing tallow fat and
      canola oil with 59% of free fatty acids. The preliminary results show that
      esterification can reach 91% conversion in the presence of the sulfonated
      polymeric catalyst compared with 67% conversion when the reaction is performed
      without catalyst. 

PMID- 24098858
TI  - Localization of premature ventricular contraction foci in normal individuals
      based on multichannel electrocardiogram signals processing.
AB  - A premature ventricular contraction (PVC) is relatively a common event where the
      heartbeat is initiated by the other pathway rather than by the Sinoatrial node,
      the normal heartbeat initiator. Determining PVC foci is important for ablation
      procedure and it can help in pre-procedural planning and potentially may improve
      ablation outcome. In this study, 12-lead Electrocardiogram (ECG) of 87 patients
      without structural cardiac diseases, who had experienced PVC, were obtained.
      Initially, PVC foci were labeled based on Electrophysiology study (EPS) reports.
      PVC beats were detected by wavelet method and their foci were classified using
      Mahalanobis distance and One-way ANOVA. Using morphological, frequency and
      spectrogram features, these foci in the heart were classified into five groups:
      Left Ventricular Outflow Tract (LVOT), Right Ventricular Outflow Tract (RVOT)
      septum, basal Right Ventricular (RV), RVOT free-wall, and Aortic Cusp (AC). The
      results showed that 88.4% of patients are classified correctly. 

PMID- 24098859
TI  - Detection of epileptic seizure using wireless sensor networks.
AB  - The monitoring of epileptic seizures is mainly done by means of
      electroencephalogram (EEG) monitoring. Although this method is accurate, it is
      not comfortable for the patient as the EEG-electrodes have to be attached to the
      scalp which hampers the patient's movement. This makes long-term home monitoring
      not feasible. In this paper, the aim is to propose a seizure detection system
      based on accelerometry for the detection of epileptic seizure. The used sensors
      are wireless, which can improve quality of life for the patients. In this system,
      three 2D accelerometer sensors are positioned on the right arm, left arm, and
      left thigh of an epileptic patient. Datasets from three patients suffering from
      severe epilepsy are used in this paper for the development of an automatic
      detection algorithm. This monitoring system is based on Wireless Sensor Networks
      and can determine the location of the patient when a seizure is detected and then
      send an alarm to hospital staff or the patient's relatives. Our wireless sensor
      nodes are MICAz Motes developed by Crossbow Technology. The proposed system can
      be used for patients living in a clinical environment or at their home, where
      they do only their daily routines. The analysis of the recorded data is done by
      an Artificial Neural Network and K Nearest-Neighbor to recognize seizure
      movements from normal movements. The results show that K Nearest Neighbor
      performs better than Artificial Neural Network for detecting these seizures. The
      results also show that if at least 50% of the signal consists of seizure samples,
      we can detect the seizure accurately. In addition, there is no need for training
      the algorithm for each new patient. 

PMID- 24098860
TI  - Disorganization of Equilibrium Directional Interactions in the Brain Motor
      Network of Parkinson's disease: New Insight of Resting State Analysis Using
      Granger Causality and Graphical Approach.
AB  - Parkinson's disease (PD) is a progressive neurological disorder characterized by
      tremor, rigidity, and slowness of movements. Particular changes related to
      various pathological attacks in PD could result in causal interactions of the
      brain network from resting state functional magnetic resonance imaging (rs-fMRI)
      data. In this paper, we aimed to disclose the network structure of the directed
      influences over the brain using multivariate Granger causality analysis and graph
      theory in patients with PD as compared with control group. rs-fMRI at rest from
      10 PD patients and 10 controls were analyzed. Topological properties of the
      networks showed that information flow in PD is smaller than that in healthy
      individuals. We found that there is a balanced local network in healthy control
      group, including positive pair-wise cross connections between caudate and
      cerebellum and reciprocal connections between motor cortex and caudate in the
      left and right hemispheres. The results showed that this local network is
      disrupted in PD due to disturbance of the interactions in the motor networks.
      These findings suggested alteration of the functional organization of the brain
      in the resting state that affects the information transmission from and to other
      brain regions related to both primary dysfunctions and higher-level cognition
      impairments in PD. Furthermore, we showed that regions with high degree values
      could be detected as betweenness centrality nodes. Our results demonstrate that
      properties of small-world connectivity could also recognize and quantify the
      characteristics of directed influence brain networks in PD. 

PMID- 24098861
TI  - Hybrid method for prediction of metastasis in breast cancer patients using gene
      expression signals.
AB  - Using primary tumor gene expression has been shown to have the ability of finding
      metastasis-driving gene markers for prediction of breast cancer recurrence (BCR).
      However, there are some difficulties associated with analysis of microarray data,
      which led to poor predictive power and inconsistency of previously introduced
      gene signatures. In this study, a hybrid method was proposed for identifying more
      predictive gene signatures from microarray datasets. Initially, the parameters of
      a Rough-Set (RS) theory based feature selection method were tuned to construct a
      customized gene extraction algorithm. Afterward, using RS gene selection method
      the most informative genes selected from six independent breast cancer datasets.
      Then, combined set of these six signature sets, containing 114 genes, was
      evaluated for prediction of BCR. In final, a meta-signature, containing 18 genes,
      selected from the combination of datasets and its prediction accuracy compared to
      the combined signature. The results of 10-fold cross-validation test showed
      acceptable misclassification error rate (MCR) over 1338 cases of breast cancer
      patients. In comparison to a recent similar work, our approach reached more than
      5% reduction in MCR using a fewer number of genes for prediction. The results
      also demonstrated 7% improvement in average accuracy in six utilized datasets,
      using the combined set of 114 genes in comparison with 18-genes meta-signature.
      In this study, a more informative gene signature was selected for prediction of
      BCR using a RS based gene extraction algorithm. To conclude, combining different
      signatures demonstrated more stable prediction over independent datasets. 

PMID- 24098862
TI  - Using protein interaction database and support vector machines to improve gene
      signatures for prediction of breast cancer recurrence.
AB  - Numerous studies used microarray gene expression data to extract metastasis
      driving gene signatures for the prediction of breast cancer relapse. However, the
      accuracy and generality of the previously introduced biomarkers are not
      acceptable for reliable usage in independent datasets. This inadequacy is
      attributed to ignoring gene interactions by simple feature selection methods, due
      to their computational burden. In this study, an integrated approach with low
      computational cost was proposed for identifying a more predictive gene signature,
      for prediction of breast cancer recurrence. First, a small set of genes was
      primarily selected as signature by an appropriate filter feature selection (FFS)
      method. Then, a binary sub-class of protein-protein interaction (PPI) network was
      used to expand the primary set by adding adjacent proteins of each gene signature
      from the PPI-network. Subsequently, the support vector machine-based recursive
      feature elimination (SVMRFE) method was applied to the expression level of all
      the genes in the expanded set. Finally, the genes with the highest score by
      SVMRFE were selected as the new biomarkers. Accuracy of the final selected
      biomarkers was evaluated to classify four datasets on breast cancer patients,
      including 800 cases, into two cohorts of poor and good prognosis. The results of
      the five-fold cross validation test, using the support vector machine as a
      classifier, showed more than 13% improvement in the average accuracy, after
      modifying the primary selected signatures. Moreover, the method used in this
      study showed a lower computational cost compared to the other PPI-based methods.
      The proposed method demonstrated more robust and accurate biomarkers using the
      PPI network, at a low computational cost. This approach could be used as a
      supplementary procedure in microarray studies after applying various gene
      selection methods. 

PMID- 24098863
TI  - Ensemble Semi-supervised Frame-work for Brain Magnetic Resonance Imaging Tissue
      Segmentation.
AB  - Brain magnetic resonance images (MRIs) tissue segmentation is one of the most
      important parts of the clinical diagnostic tools. Pixel classification methods
      have been frequently used in the image segmentation with two supervised and
      unsupervised approaches up to now. Supervised segmentation methods lead to high
      accuracy, but they need a large amount of labeled data, which is hard, expensive,
      and slow to obtain. Moreover, they cannot use unlabeled data to train
      classifiers. On the other hand, unsupervised segmentation methods have no prior
      knowledge and lead to low level of performance. However, semi-supervised learning
      which uses a few labeled data together with a large amount of unlabeled data
      causes higher accuracy with less trouble. In this paper, we propose an ensemble
      semi-supervised frame-work for segmenting of brain magnetic resonance imaging
      (MRI) tissues that it has been used results of several semi-supervised
      classifiers simultaneously. Selecting appropriate classifiers has a significant
      role in the performance of this frame-work. Hence, in this paper, we present two
      semi-supervised algorithms expectation filtering maximization and MCo_Training
      that are improved versions of semi-supervised methods expectation maximization
      and Co_Training and increase segmentation accuracy. Afterward, we use these
      improved classifiers together with graph-based semi-supervised classifier as
      components of the ensemble frame-work. Experimental results show that performance
      of segmentation in this approach is higher than both supervised methods and the
      individual semi-supervised classifiers. 

PMID- 24098864
TI  - Optimizing of the tangential technique and supraclavicular fields in 3
      dimensional conformal radiation therapy for breast cancer.
AB  - Radiotherapy plays an essential role in the management of breast cancer. Three
      dimensional conformal radiation therapy (3D-CRT) is applied based on 3D image
      information of anatomy of patients. In 3D-CRT for breast cancer one of the common
      techniques is tangential technique. In this project, various parameters of
      tangential and supraclavicular fields are optimized. This project has been done
      on computed tomography images of 100 patients in Isfahan Milad Hospital. All
      patients have been simulated and all the important organs have been contoured by
      radiation oncologist. Two techniques in supraclavicular region are evaluated
      including: 1-A single field (Anterior Posterior [AP]) with a dose of 200 cGy per
      fraction with 6 MV energy. This is a common technique. 2-Two parallel opposed
      fields (AP-Posterior Anterior [PA]). The dose of AP was 150 cGy with 6 MV energy
      and PA 50 cGy with 18 MV. In the second part of the project, the tangential
      fields has been optimized with change of normalization point in five points: (1)
      Isocenter (Confluence of rotation gantry axis and collimator axis) (2) Middle of
      thickest part of breast or middle of inter field distance (IFD) (3) Border
      between the lung and chest wall (4) Physician's choice (5) Between IFD and
      isocenter. Dose distributions have been compared for all patients in different
      methods of supraclavicular and tangential field. In parallel opposed fields
      average lung dose was 4% more than a single field and the maximum received heart
      dose was 21.5% less than a single field. The average dose of planning tumor
      volume (PTV) in method 2 is 2% more than method 1. In general AP-PA method
      because of a better coverage of PTV is suggested. In optimization of the
      tangential field all methods have similar coverage of PTV. Each method has
      spatial advantages and disadvantages. If it is important for the physician to
      reduce the dose received by the lung and heart, fifth method is suggested since
      in this method average and maximum received dose to heart and lung have been
      reduced few percent in comparison to other methods. If a better coverage of PTV
      is important for the physician second method can be an optimized method. In this
      method, average and maximum received dose to PTV have been increased few percent
      in comparisons of physician's choice method and three other methods. In
      optimizing of supraclavicular field AP-PA method due to better coverage of PTV is
      suggested. In optimizing of tangential all methods are similar. Each method has
      special advantages and disadvantages. The physicians can change the depth of the
      normalization point in the breast to get the desired average dose. 

PMID- 24098865
TI  - Introducing kernel based morphology as an enhancement method for mass
      classification on mammography.
AB  - Since mammography images are in low-contrast, applying enhancement techniques as
      a pre-processing step are wisely recommended in the classification of the
      abnormal lesions into benign or malignant. A new kind of structural enhancement
      is proposed by morphological operator, which introduces an optimal Gaussian
      Kernel primitive, the kernel parameters are optimized the use of Genetic
      Algorithm. We also take the advantages of optical density (OD) images to promote
      the diagnosis rate. The proposed enhancement method is applied on both the gray
      level (GL) images and their OD values respectively, as a result morphological
      patterns get bolder on GL images; then, local binary patterns are extracted from
      this kind of images. Applying the enhancement method on OD images causes more
      differences between the values therefore a threshold method is applied toremove
      some background pixels. Those pixels that are more eligible to be mass are
      remained, and some statistical texture features are extracted from their
      equivalent GL images. Support vector machine is used for both approaches and the
      final decision is made by combining these two classifiers. The classification
      performance rate is evaluated by Az, under the receiver operating characteristic
      curve. The designed method yields Az = 0.9231, which demonstrates good results. 

PMID- 24098866
TI  - Reply to the letter sent by prof. Viroj wiwanitkit entitled "radiofrequency
      radiation and human ferritin".

PMID- 24098867
TI  - Step-Height Measurement of Surface Functionalized Micromachined Microcantilever
      Using Scanning White Light Interferometry.
AB  - Micro-cantilever arrays with different dimensions are fabricated by
      micromachining technique onto silicon <1 0 0> substrate. These sputtered Gold
      Coated micro-cantilevers were later surface functionalized. Scanning Electron
      Microscopy, Atomic Force Microscopy and Optical SWLI using LASER probe are
      employed to characterize the morphology and image measurement of the micro
      cantilever arrays, respectively. Compared with conventional AFM and SPM
      measurement technique, the proposed method has demonstrated sufficient
      flexibility and reliability. The experimental results have been analyzed and
      presented in this paper for MEMS Micro-cantilevers. The scanning White Light
      Interferometry based two point high resolution optical method is presented for
      characterizing Micro-cantilevers and other MEMS micro-structures. The repeatable
      error and the repeatable precision produced in the proposed image measurement
      method is nanometre confirmable. In this piece of work, we investigate the micro
      structure fabrication and image measurement of Length, Width and Step-Height of
      micro-cantilever arrays fabricated using bulk micromachining technique onto
      Silicon <100> substrate.

PMID- 24098869
TI  - Spectrally resolved photon-echo spectroscopy of Rhodamine-6G.
AB  - Wavelength dependent study of a laser dye: Rhodamine-6G (Rh6G) by using
      spectrally resolved photon-echo spectroscopy is presented. The coherence and
      population dynamics of Rh6G solution in methanol changes as the excitation
      wavelength is tuned near its absorption maxima of 528 nm. Specifically, the
      central wavelength of the femtosecond laser pulse was set to 535 nm and to 560 nm
      while the respective spectra of the photon-echo signals were collected. This
      gives information on how the ultrafast dynamics of the Rh6G molecule changes with
      a change in the excitation wavelength.

PMID- 24098870
TI  - No substitute for experience: do consultants that have been practising for longer
      lead faster post-take medical ward rounds?
AB  - AIM: To ascertain whether consultants that have been practising for longer lead
      faster post-take medical ward rounds. METHOD: Single-centre observational study
      of nine consultant physicians at morning post-take medical ward rounds at a
      district general hospital in the North West of London. RESULTS: Data were
      gathered from 25 post-take medical ward rounds. Multivariate regression analysis
      revealed that less time is spent per patient when consultants have been
      practising for longer (p<0.01), or have spent more time on the specialist
      register (p<0.01), with no discernible relation to the outcomes for the patients
      seen. This time is further reduced when a greater number of patients are seen on
      the ward round. CONCLUSION: More experienced consultant physicians conduct faster
      post-take medical ward rounds.

PMID- 24098871
TI  - Measuring hospital mortality.
AB  - The hospital standardised mortality ratio (HSMR) and the summary hospital
      mortality index (SHMI) are both in current use in the UK as measures of the
      performance of acute hospitals. Characteristics of both the acute hospital itself
      and of its local healthcare environment influence these indices. Whilst many hope
      that measures of mortality can be used as a surrogate for healthcare quality,
      this is an evolving area. 

PMID- 24098868
TI  - The Role of PARP Inhibitors in the Treatment of Gynecologic Malignancies.
AB  - Gynecologic malignancies annually account for over 91,000 new cancer cases and
      approximately 28,000 deaths in the United States. Although there have been
      advancements in cytotoxic chemotherapies, there has not been significant
      improvement in overall survival in these patients. While targeted therapies have
      shown some benefit in many solid tumors, further development of these agents is
      needed for the treatment of gynecologic malignancies. Poly(ADP-ribose) polymerase
      (PARP) catalyzes the polyADP-ribosylation of proteins involved in DNA repair.
      Inhibitors of PARP were originally developed for cancers with homologous
      recombination deficiencies, such as those harboring mutations in BRCA1 or BRCA2
      genes. However, pre-clinical research and clinical trials have suggested that the
      activity of PARP inhibitors is not limited to those with BRCA mutations. PARP
      inhibitors may have activity in cancers deficient in other DNA repair genes,
      signaling pathways that mitigate DNA repair, or in combination with DNA-damaging
      agents independent of DNA repair dysfunction. Currently there are seven different
      PARP inhibitors in clinical development for cancer. While there has been
      promising clinical activity for some of these agents, there are still significant
      unanswered questions regarding their use. Going forward, specific questions that
      must be answered include timing of therapy, use in combination with cytotoxic
      agents or as single-agent maintenance therapy, and whether there is a predictive
      biomarker that can be used with PARP inhibition. Even with large strides in the
      treatment of many gynecologic malignancies in recent years, it is imperative that
      we develop newer agents and methods to identify patients that may benefit from
      these compounds. The focus of this review will be on pre-clinical data, current
      clinical trials, and the future of PARP inhibitors in the treatment of ovarian,
      endometrial, and cervical cancer. 

PMID- 24098872
TI  - Performance of TOTAL, in medical patients attending a resource-poor hospital in
      sub-Saharan Africa and a small Irish rural hospital.
AB  - BACKGROUND: Recently a very simple, easy to remember early warning score (EWS)
      dubbed TOTAL has been reported. The score was derived from 309 acutely ill
      medical patients admitted to a Malawian hospital and awards one point for
      Tachypnea >30 breaths per minute, one point for Oxygen saturation <90%, two
      points for a Temperature <35 degrees C, one point for Altered mental status, and
      one point for Loss of independence as indicated by the inability to stand or walk
      without help. TOTAL has an area under the receiver operator characteristic curve
      (AUROC) for death within 72 hours of 78%. METHODS: We compared the performance of
      the TOTAL score in 849 medical patients attending a resource poor hospital in
      Uganda and 2935 patients admitted to a small rural hospital in Ireland. RESULTS:
      TOTAL's AUROC for death within 24 hours was the same in both hospital
      populations: 85.1% (95% CI 78.6 - 91.6%) for Kitovu Hospital patients and 84.7%
      (95% CI 77.1 - 92.2%) for Nenagh Hospital patients. CONCLUSION: The
      discrimination of TOTAL is exactly the same in elderly Irish patients as it is in
      young African patients. The score is easy to remember, easy to calculate, and
      works over a broad range of patients.

PMID- 24098873
TI  - Exercise stress test utility in patients with chest pain presumed to be of
      cardiac origin.
AB  - INTRODUCTION: NICE stated exercise stress tests (EST) should not be used to
      diagnose obstructive coronary artery disease in patients presenting with chest
      pain presumed to be of cardiac origin. METHODS: A retrospective review of 209
      patients with presumed cardiac chest pain was done. EST results, GRACE scores and
      need for invasive coronary angiogram (ICA) were analysed to predict the need for
      readmission, intervention and future events. RESULTS: The sensitivity of the EST
      in identifying obstructive coronary artery disease was 70%. The EST, ICA and the
      GRACE 6-month mortality had a 77%, 70% and 81% negative predictive value (NPV)
      for readmission respectively. CONCLUSION: EST, GRACE scores and ICA are useful in
      providing prognostic information but are poor predictors of readmission. Follow
      up and education programmes are needed to reduce this burden.

PMID- 24098874
TI  - Acute care simulation training for foundation doctors: the perceived impact on
      practice in the workplace.
AB  - High fidelity simulation allows training of foundation doctors in a safe,
      structured environment. We explored the perceived impact of such training on
      subsequent clinical practice. 82 doctors attended and 52% responded to a follow
      up questionnaire sent two months after their training. 88% felt better able to
      manage the acutely ill patient than they did before their training. All cited
      simulation training as a reason for this and 44% felt simulation training was the
      main contributor. The remainder cited clinical experience as the main
      contributor. 53% gave real clinical examples where they applied skills attributed
      to simulation training. Doctors reflected positively on simulation training
      sometime after the experience, demonstrated transference of learnt skills and
      felt more confident at work. 

PMID- 24098875
TI  - The vanishing lung: an important cause of hyperlucency on chest radiograph.
AB  - Giant bullous emphysema is an uncommon condition characterised by large
      asymmetric bullae with upper lobe predominance. This condition is most frequent
      in young male smokers. Patients usually present with progressive breathlessness
      which is secondary to enlargement of the bullae leading to compression of the
      lung parenchyma. Large asymmetrical bullae may appear as a unilateral
      hyperlucency on a plain chest radiograph, and may mimic the appearances of
      pneumothorax. A computed tomography scan is needed to delineate the lung
      pathology. We describe two cases with this condition that presented acutely and
      discuss the management of bullous emphysema. 

PMID- 24098876
TI  - Abdominal pain and a raised amylase? It's not always pancreatitis. . .
AB  - We report the case of a 72 year old man with a history of COPD and heavy alcohol
      consumption who was initially diagnosed with acute pancreatitis based on a
      presentation with epigastric pain and elevated serum amylase. Review of his notes
      revealed several previous similar admissions and extensive normal investigations
      apart from persistently elevated amylase. Further analysis showed evidence of
      macroamylasaemia which accounted for the apparently high serum amylase level. 

PMID- 24098877
TI  - Problem based review: the patient who has taken an overdose of long-acting
      insulin analogue.
AB  - Insulin overdose can cause harm due to hypoglycaemia, effects on electrolytes and
      acute hepatic injury. The established long-acting insulin analogue preparations
      (detemir and glargine) can present specific management problems because, in
      overdose, their effects are extremely prolonged, often lasting 48-96 hours. The
      primary treatment is continuous intravenous 10% or 20% glucose infusion with
      frequent capillary blood glucose monitoring. Surgical excision of the insulin
      injection site has been used successfully, even days after the overdose occurred.
      Once the effects of overdose have receded, diabetes treatment must be restarted
      with care, especially in patients with type 1 diabetes. Monitoring serum insulin
      concentration has been successfully used to predict when the effects of the
      overdose will cease. 

PMID- 24098878
TI  - The patient presenting with 'acopia'.
AB  - Patients may be referred to Acute Medical Units (AMUs) with a diagnosis of
      'acopia'. This term is offensive and lazy, implying fault on the part of the
      patient and allowing the assessing doctor to erroneously label the patient as a
      'social admission' when, in fact, such patients are likely to be frail with co
      morbidities and have an acute (potentially reversible) illness. Frail older
      patients should be assessed using the principles of Comprehensive Geriatric
      Assessment, informed by an understanding of the concept of frailty and of
      geriatric syndromes such as falls and delirium. 

PMID- 24098879
TI  - Summary Care Records in urgent and emergency care in England.
AB  - Summary Care Records (SCRs) have been created for more than 50% of the population
      of England. The number is increasing at about 100,000 records a week. Fewer than
      1.5% of people have elected not to have a SCR. SCRs contain updated details of
      patient medication, allergies and adverse reactions, electronically extracted
      from the GP record. A patient and their GP can also agree to have additional
      information included. SCRs are being viewed by authorised healthcare staff in
      urgent and emergency care settings all over England. Benefits are being reported
      in relation to increased patient safety, improved clinical decision making,
      improved efficiency and improved quality of care. NHS England strongly supports
      the uptake and adoption of SCRs by Trusts in England. 

PMID- 24098880
TI  - Optical fiber sensor for the detection of tetracycline using surface plasmon
      resonance and molecular imprinting.
AB  - We present a simple and highly selective optical fiber sensor for the detection
      of tetracycline in foodstuffs by using the combination of surface plasmon
      resonance (SPR) and a molecular imprinted polymer (MIP) matrix. The sensor is
      fabricated first by coating a thin film of silver metal over the unclad portion
      of an optical fiber, and then preparing a molecular imprinting of the target
      molecules over the metal coated region. The MIP creates several binding
      sites/nano-cavities which have the complementary shape and functional groups of
      the target molecules on its surface. The sensor works on the wavelength
      modulation scheme in which the shift in resonance wavelength is measured with
      respect to the change in tetracycline concentration. Two kinds of tetracycline,
      tetracycline hydrochloride (TC) and oxy-tetracycline hydrochloride (OTC) have
      been selected as the imprinting molecules because these possess similar
      structures. The presence of tetracycline samples in the vicinity of the sensing
      region causes the interaction between binding sites and target molecules which
      results in the change in the dielectric properties of the sensing surface,
      causing the shift in the SPR spectrum towards the red region. The selectivity of
      the sensor for dissimilar compounds, and cross-selectivity between TC and OTC,
      has been tested. The reusability of the sensor has also been checked. The present
      sensor is suitable for commercialization for the detection of tetracycline in
      food as it has several advantageous features such as low cost, ease of handling,
      a miniaturized probe, fast response, high selectivity, reusability and the
      possibility of online monitoring and remote sensing. 

PMID- 24098881
TI  - Fluorescence assay for glycan expression on living cancer cells based on
      competitive strategy coupled with dual-functionalized nanobiocomposites.
AB  - Cell surface glycans are a class of sophisticated biomolecules related to cancer
      development and progression, and their analysis is of great significance for
      early cancer diagnosis and treatment. In this paper, we proposed a fluorescence
      assay to evaluate glycan expression on living cancer cells based on a competitive
      strategy coupled with dual-functionalized nanobiocomposites. The competitive
      assay was conducted between living cancer cells and thiomannosyl derivatives
      using concanavalin A (Con A)-modified electrode as the interaction platform. To
      impart fluorescence signaling ability to competitive derivatives, quantum dots
      (QDs) were anchored on BSA-protected Au nanoparticles, and thiomannosyl
      derivatives were further immobilized on the nanoparticle surface through Au-S
      binding. Due to the spacing between QDs and Au nanoparticles by BSA, the {QDs-Au
      BSA-mannose} nanobiocomposites maintained the fluorescence of QDs and showed
      binding ability with the Con A-modified electrode. Au nanorods (AuNRs)-modified
      electrode was used as an effective substrate to immobilize Con A. This assay was
      successfully applied to the analysis of two cancer cells lines (A549 and QGY
      7701). The method is simple and shows promise for the study of glycan expression
      on living cancer cells. 

PMID- 24098882
TI  - An octachlorostyrene electrochemical immunosensor: double amplification
      strategies with immobilization of nano-Au and Au nanoparticle labels.
AB  - Anti-octachlorostyrene (OCS) antibody was derived from an immune rabbit
      preparation. An OCS immunosensor was constructed by immobilizing the anti-OCS
      antibody on a glassy carbon electrode coated with chitosan and gold nanoparticles
      (AuNPs, ~5 nm, represented as AuNP05). Large-sized AuNPs (~90 nm, represented as
      AuNP90) were used as the electrochemical label. The AuNP90-labeled OCS competes
      with the target OCS for the limited antibody molecules immobilized on the sensor
      surface. The amount of bound AuNP90 is inversely proportional to the OCS
      concentration. OCS was quantified based on the bound AuNP90 which was detected by
      differential pulse voltammetry (DPV), i.e. the AuNP90 was firstly electrooxidized
      in 0.1 M HCl to produce AuCl4(-), then the reduction current of AuCl4(-) was
      detected. The immobilized AuNP05 increases the loading of anti-OCS antibody. Both
      the immobilized AuNP05 and the label AuNP90 amplify the sensor response. The
      proposed electrochemical immunosensor exhibits high selectivity, good storage
      stability, and high sensitivity with a linear range from 1 to 500 nM (R(2) =
      0.971) and a detection limit of 0.4 nM. 

PMID- 24098883
TI  - A potentiometric tattoo sensor for monitoring ammonium in sweat.
AB  - The development and analytical characterization of a novel ion-selective
      potentiometric cell in a temporary-transfer tattoo platform for monitoring
      ammonium levels in sweat is presented. The fabrication of this skin-worn sensor,
      which is based on a screen-printed design, incorporates all-solid-state
      potentiometric sensor technology for both the working and reference electrodes,
      in connection to ammonium-selective polymeric membrane based on the nonactin
      ionophore. The resulting tattooed potentiometric sensor exhibits a working range
      between 10(-4) M to 0.1 M, well within the physiological levels of ammonium in
      sweat. Testing under stringent mechanical stress expected on the epidermis shows
      that the analytical performance is not affected by factors such as stretching or
      bending. Since the levels of ammonium are related to the breakdown of proteins,
      the new wearable potentiometric tattoo sensor offers considerable promise for
      monitoring sport performance or detecting metabolic disorders in healthcare. Such
      combination of the epidermal integration, screen-printed technology and
      potentiometric sensing represents an attractive path towards non-invasive
      monitoring of a variety of electrolytes in human perspiration. 

PMID- 24098884
TI  - Honeycomb-patterned phthalocyanine films with photo-active antibacterial
      activities.
AB  - We report honeycomb-patterned phthalocyanine (Pc) films fabricated by self
      assembly of dodecyloxy-azo-Zinc phthalocyanine (daZnPc) using the breath figure
      (BF) technique. These ultrathin Pc films exhibit a robust photo-dependent
      antibacterial effect against Escherichia coli (E. coli). 

PMID- 24098885
TI  - "One pot" regiospecific synthesis of polysubstituted pyrroles from benzylamines
      and ynones under metal free conditions.
AB  - A convenient "one-pot" weak base-promoted synthesis of polysubstituted pyrroles
      has been developed from benzylamines and ynones. This transformation involves the
      Michael addition reaction and intramolecular condensation, which features high
      regioselectivity, high efficiency, environmental friendliness and metal free. A
      series of polysubstituted pyrroles were provided in up to 91% yield for 27
      examples. 

PMID- 24098886
TI  - Colorimetric detection of human papilloma virus by double isothermal
      amplification.
AB  - We developed a polymerase reaction free, low-cost and sensitive assay for the
      colorimetric detection of Human Papilloma Virus (HPV), based on the use of a
      smart design exploiting magnetic microbeads, chimeric RNA/DNAzyme
      oligonucleotides, and double signal amplification. This method allows obtaining a
      fast response with a detection limit of 10 pM, avoiding the amplification of the
      target via traditional PCR. 

PMID- 24098887
TI  - Liquid crystalline 2-thienyl-4,6-diamino-1,3,5-triazines exhibiting Im3[combining
      macron]m and Pm3[combining macron]n micellar cubic phases in an inverted
      sequence.
AB  - Two micellar cubic phases with different structures were observed for the first
      time in the order Im3[combining macron]m-Pm3[combining macron]n in a thermotropic
      phase sequence of 4,6-diaminotriazine terminated rod-like liquid crystals upon
      increasing alkyl chain length or rising temperature. 

PMID- 24098888
TI  - Dual role of allylsamarium bromide as a Grignard reagent and a single electron
      transfer reagent in the one-pot synthesis of terminal olefins.
AB  - The utility of allylsamarium bromide, both as a nucleophilic reagent and a single
      electron transfer reagent, in the reaction of carbonyl compounds with
      allylsamarium bromide in the presence of diethyl phosphate is reported in this
      communication. From a synthetic point of view, a simple one-pot method for the
      preparation of terminal olefins is developed. 

PMID- 24098889
TI  - Substrate selective catalytic molecular hydrogels: the role of the hydrophobic
      effect.
AB  - A catalytic hydrogel is reported for the substrate selective direct aldol
      reaction of aliphatic ketones based on their hydrophobicity and on the emergence
      of catalytic activity only after self-assembly of the catalyst. 

PMID- 24098890
TI  - A functionalized MIL-101(Cr) metal-organic framework for enhanced hydrogen
      release from ammonia borane at low temperature.
AB  - Hydrogen released from ammonia borane in MIL-101(Cr) can be significantly
      improved by the attached amino and amide groups. The release with minimum
      impurities starts at 68  degrees C, reaching 1.6 equivalent of ammonia borane at
      85  degrees C for the amino modified MOFs (NH2-MIL-101). 

PMID- 24098891
TI  - Enantioselective synthesis of alpha-nitro-delta-ketosulfones via a quinine
      squaramide catalyzed conjugate addition of alpha-nitrosulfones to enones.
AB  - Conjugate addition of alpha-nitrosulfones to vinyl ketones in the presence of 0.2
      mol% of a quinine-squaramide organocatalyst afforded alpha-nitro-delta
      ketosulfones possessing a tetrasubstituted chiral center in excellent yield and
      enantioselectivity in most cases. This strategy also offers a facile and
      convenient entry into gamma-sulfonylhydroxamates that are one carbon homologs of
      potent enzyme inhibitors. 

PMID- 24098892
TI  - A near-infrared dye based on BODIPY for tracking morphology changes in
      mitochondria.
AB  - M-DPT, a BODIPY-based water soluble near-infrared fluorescent probe with
      thiophene at the 1,7-position, is synthesized. M-DPT is found to possess high
      specificity to mitochondria, superior photostability, and appreciable tolerance
      to microenvironmental changes. Thus, this probe is a highly suitable imaging
      agent for targeting mitochondria and tracking morphology changes.

PMID- 24098893
TI  - Lotus leaf-inspired CVD grown graphene for a water repellant flexible transparent
      electrode.
AB  - By simply heating commercial copper foil under an oxygen atmosphere and
      subsequently annealing CuO under a hydrogen atmosphere, the 3D Cu structures in
      the form of double hierarchical bumps are generated. The contact angle of a lotus
      leaf-inspired graphene grown on the reconstructed 3D Cu structures is 154.2
      degrees . 

PMID- 24098894
TI  - Polymer-induced inverse-temperature crystallization of nanoparticles on a
      substrate.
AB  - Using molecular dynamics simulations, we study the properties of liquid state
      polymer-nanoparticle composites confined between two parallel substrates, with an
      attractive polymer-substrate interaction. Polymers are in the semidilute regime
      at concentrations far above the overlap point, and nanoparticles are in good
      solvent and without enthalpic attraction to the substrates. An increase of
      temperature then triggers the crystallization of nanoparticles on one of the two
      substrate surfaces-a surprising phenomenon, which is explained in terms of
      scaling theory, such as through competing effects of adsorption-and correlation
      blobs. Moreover, we show that the first, closely packed layer of nanoparticles on
      the substrate increases the depletion attraction of additional nanoparticles from
      the bulk, thereby enhancing and stabilizing the formation of a crystalline phase
      on the substrate. Within the time frame accessible to our numerical simulations,
      the crystallization of nanoparticles was irreversible; that is, their crystalline
      phase, once created, remained undamaged after a decrease of the temperature. Our
      study leads to a class of thermoreactive nanomaterials, in which the transition
      between a homogeneous state with dissolved nanoparticles and a surface
      crystallized state is triggered by a temperature jump. 

PMID- 24098895
TI  - Photoredox-mediated C-H functionalization and coupling of tertiary aliphatic
      amines with 2-chloroazoles.
AB  - Herein, conditions for C-H functionalization of tertiary aliphatic amines and
      their subsequent coupling with a number of 2-chloroazole derivatives are
      reported. The reaction is facilitated by a catalytic amount of tris-fac-Ir(ppy)3,
      with blue light irradiation and takes place under mild and convenient conditions.
      Most couplings take place with excellent regioselectivity. The reaction is
      tolerant of a number of functional groups and allows for rapid access to alpha
      azole carbinamines commonly found in post-translationally modified peptides. 

PMID- 24098896
TI  - Multisystemic diseases and ethnicity: a focus on lupus erythematosus, systemic
      sclerosis, sarcoidosis and Behcet disease.
AB  - We present an overview of the association between ethnicity and the clinical and
      epidemiological aspects of four multisystemic diseases: lupus erythematosus,
      systemic sclerosis, sarcoidosis and Behcet disease. In particular, we highlight
      observed ethnic differences in cutaneous manifestations of these diseases. This
      article should help guide clinical management, as well as serve to highlight
      future areas for research. 

PMID- 24098897
TI  - The impact of human immunodeficiency virus-related diseases on pigmented skin
      types.
AB  - Infection with human immunodeficiency virus (HIV) remains a significant problem
      globally. Early diagnosis and treatment with antiretroviral drugs has
      considerably improved health outcomes and decreased disease-related morbidity.
      HIV infection is associated with a wide range of skin disorders enabling
      dermatologists to diagnose HIV as well as associated opportunistic infections
      early in the course of disease. Despite concerted efforts by international health
      organizations to limit disease incidence, the prevalence of HIV infection remains
      high and is highest in sub-Saharan Africa. The diagnosis of HIV-related skin
      diseases is challenging as immunosuppression often results in atypical disease
      presentation. In addition, the clinical presentation will vary in pigmented skin
      types. The aim of this article is to describe disease variation in pigmented skin
      types. 

PMID- 24098898
TI  - Hair and scalp disorders in women of African descent: an overview.
AB  - We present an overview of hair and scalp disorders in women of African descent,
      discussing the biological features of afro-textured hair, as well as hair
      grooming practices in this cohort and their association with specific hair and
      scalp disorders. A practical approach to diagnosing and managing common hair and
      scalp disorders in this cohort is also presented. 

PMID- 24098899
TI  - Variations in skin colour and the biological consequences of ultraviolet
      radiation exposure.
AB  - Harmful consequences of sun exposure range from sunburn, photoageing and
      pigmentary disorders to skin cancer. The incidence and extent of these
      detrimental effects are largely due to the degree of constitutive pigmentation of
      the skin. The latter can be objectively classified according to the individual
      typology angle ( degrees ITA) based on colorimetric parameters. The physiological
      relevance of the ITA colorimetric classification was assessed in 3500 women
      living in various geographical areas. Furthermore, in order to understand the
      relationship between constitutive pigmentation and ultraviolet radiation (UVR)
      sensitivity, we worked on ex vivo human skin samples of different colour exposed
      to increasing UVR doses. For each sample we defined the biologically efficient
      dose (BED), based on the induction of sunburn cells, and analysed UVR-induced DNA
      damage (cyclobutane thymine dimers, CPD). We found a significant correlation
      between ITA and BED. We also found a correlation between ITA and DNA damage. As
      the epidermal basal layer also hosts melanocytes and in order to analyse the
      relationship between skin colour and DNA damage occurring specifically within
      this cell type, we performed double staining for CPD and tyrosinase-related
      protein (TRP) 1, a key enzyme in melanin synthesis. We found that DNA damage
      within melanocytes depends on ITA. Taken together our results may explain the
      higher risk of lighter skin types developing skin cancers, including melanoma, as
      well as the development of pigmentary disorders in moderately pigmented skin.
      They show that skin classification based on ITA is physiologically relevant (as
      it correlates with constitutive pigmentation) and further support the concept of
      a more personalized approach to photoprotection that corresponds to a particular
      skin colour type's sensitivity to solar UVR. 

PMID- 24098900
TI  - Facial hyperpigmentation: causes and treatment.
AB  - By midcentury, the U.S.A. will be more ethnically and racially diverse. Skin of
      colour will soon constitute nearly one-half of the U.S. population, and a full
      understanding of skin conditions that affect this group is of great importance.
      Structural and functional differences in the skin, as well as the influence of
      cultural practices, produce variances in skin disease and presentation based on
      skin type. In the skin of colour population, dyschromia is a growing concern, and
      a top chief complaint when patients present to the physician. A thorough
      understanding of the aetiology and management strategies of facial
      hyperpigmentation is of importance in caring for those afflicted and also in the
      development of new therapies. 

PMID- 24098901
TI  - Surgical interventions for vitiligo: an evidence-based review.
AB  - BACKGROUND: Vitiligo is a disfiguring disease, characterized frequently by the
      presence of de-pigmented macules and/or patches. Traditional therapies are
      essentially medical and are most preferred by dermatologists. Surgical therapies,
      however, are amongst the most effective interventions for vitiligo but are
      limited by their invasive nature, as well as the training and expertise needed to
      perform specific procedures. OBJECTIVES: To assess the evidence for the
      effectiveness, safety and applicability of the various surgical methods in the
      treatment of vitiligo. METHODS: For this systematic review of vitiligo surgical
      therapies, our searches included: PubMed, MEDLINE and Cochrane databases.
      RESULTS: We reviewed research studies reporting on split thickness skin grafts
      (STSG), punch/mini-graft, blister roof grafting, cultured and non-cultured
      cellular transplantation (MKTP). While all methods vary in their repigmentation
      outcomes, STSG is found to have the highest repigmentation success rate. Overall,
      post-operative complications included milia, scarring, cobblestone appearance or
      hyperpigmentation of treated areas. CONCLUSION: This review highlights the need
      for more randomized controlled trials in this field, underpinned by a more
      standardized objective approach to the assessment of repigmentation following
      surgical interventions.

PMID- 24098902
TI  - Future horizons in vitiligo research: focusing on the recommendations of the
      Cochrane systematic review 'Interventions for vitiligo' 2010.
AB  - The 'Implications for research' section of the Cochrane systematic review,
      'Interventions for vitiligo', published in 2010, highlighted three main issues
      that impact the standard of vitiligo research: (i) lack of consensus on the
      classification and definition of vitiligo; (ii) lack of consensus on the methods
      of assessment and outcome measures for vitiligo; and (iii) heterogeneity of
      interventions compared. This article provides an update of the progress made to
      resolve these issues since the publication of the Cochrane systematic review in
      2010, 'Interventions for vitiligo'. 

PMID- 24098903
TI  - Strategic management of keloid disease in ethnic skin: a structured approach
      supported by the emerging literature.
AB  - Keloid disease (KD) is a common, benign, dermal fibroproliferative growth of
      unknown aetiology. Lesions tend to grow over time; they often recur following
      therapy and do not regress spontaneously. KD causes considerable discomfort due
      to pain, pruritus and inflammation, and a significant psychosocial impact with
      reduced quality of life. It is unique to humans and occurrence is higher in
      individuals with dark, pigmented, ethnic skin. There is a strong familial
      heritability, with a high ethnic predisposition in individuals of African, Asian
      and Hispanic descent. High recurrence rates and unknown resolution rates present
      a major problem for both the patient and clinician. Many treatment modalities
      exist; however, there is no single advocated therapy. Therefore, the aim of this
      review was to explore the most current literature regarding the range of
      treatment options for KD and to offer a structured approach in the management of
      KD, based on evidence and experience, to aid clinicians in their current
      practice. A focused history involving careful evaluation of the patient's
      symptoms, signs, quality of life and psychosocial well-being should direct
      targeted therapy, complemented with regular follow-up and re-evaluation. Many
      treatment modalities, such as intralesional steroid injection, silicone gel
      application, cryotherapy, lasers, 5-fluorouracil and, relatively recently,
      photodynamic therapy, are currently being used in clinical practice for the
      management of KD. Combination therapies have also been shown to be beneficial.
      However, there is a lack of robust, randomized, level-one, evidence-controlled
      trials evaluating these treatment options. Management of KD in ethnic pigmented
      skin remains a clinical challenge. Thus, a strategic approach with structured
      assessment, targeted therapy and focus on prevention of recurrence is highly
      recommended. Quality evidence is essential in order to tailor treatment
      effectively for the ethnic patient presenting with KD. 

PMID- 24098904
TI  - Chemical peeling in ethnic skin: an update.
AB  - With the growth of cosmetic dermatology worldwide, treatments that are effective
      against skin diseases and augment beauty without prolonged recovery periods, or
      exposing patients to the risks of surgery, are increasing in popularity. Chemical
      peels are a commonly used, fast, safe and effective clinic room treatment that
      may be used for cosmetic purposes, such as for fine lines and photoageing, but
      also as primary or adjunct therapies for acne, pigmentary disorders and scarring.
      Clinicians are faced with specific challenges when using peels on ethnic skin
      (skin of colour). The higher risk of postinflammatory dyschromias and abnormal
      scarring makes peels potentially disfiguring. Clinicians should therefore have a
      sound knowledge of the various peels available and their safety in ethnic skin.
      This article aims to review the background, classification, various preparations,
      indications, patient assessment and complications of using chemical peels in
      ethnic skin. 

PMID- 24098905
TI  - Lasers and light-based therapies in ethnic skin: treatment options and
      recommendations for Fitzpatrick skin types V and VI.
AB  - Ethnic skin or 'skin of colour', which is characterized by increased epidermal
      melanin, labile melanocytes and reactive fibroblast responses, poses special
      challenges for the use of laser and light-based therapies. These therapies are
      associated with a greater risk of dyspigmentation and scarring in ethnic skin and
      therefore require careful selection of device and treatment parameters to
      minimize complications. Whereas early-generation lasers for hair removal and
      resurfacing were generally contraindicated for individuals with Fitzpatrick skin
      phototypes (SPT) IV-VI, advances in the past decade have given rise to a range of
      devices that can be safely used in ethnic skin. Longer wavelength lasers such as
      the 810 and 1064 nm Nd:YAG; intense pulsed light and monochromatic excimer light
      (308 nm); fractional lasers; and radiofrequency devices have all been used safely
      for hair removal, pigmentary abnormalities, resurfacing and skin tightening in
      ethnic skin, respectively. Notwithstanding these advances, nuances in the laser
      or light treatment of darker skin types remain and must be considered to ensure
      safe therapeutic outcomes. The vast majority of published data pertaining to
      lasers and light treatments in nonwhite skin involve patients of East Asian
      ethnicity (e.g. Korean, Japanese, Chinese, Thai). By contrast, there is a paucity
      of studies involving individuals of African ancestry or those with SPT V or VI.
      This article will review laser and light-based modalities that are considered
      safe and effective for individuals with richly pigmented skin.

PMID- 24098906
TI  - Ushering in a new era for studying human cutaneous diversity.

PMID- 24098907
TI  - 'Ethnic skin' and why the study of human cutaneous diversity is important.

PMID- 24098908
TI  - Life devoted to viruses and interferon: Charles Chany (1920-2013).

PMID- 24098909
TI  - Advances in the formulations of non-injection administration of docetaxel.
AB  - Docetaxel is one of the most important anti-tumor drugs and has shown powerful
      therapeutic activity against breast cancer, non-small cell lung cancer, prostate
      cancer and so on. Owing to its poor water solubility and the efflux by P
      glycoprotein (P-gp) and metabolism by CYP3A4 enzymes, it is generally
      administered as an injection form, the only manner for the current clinical
      application. However, the injection bearing polysorbate 80 and ethanol may cause
      adverse events such as severe hypersensitivity reactions, neutropenia,
      neurotoxicity, musculoskeletal toxicity and cumulative fluid retention, these
      adverse events limit clinical application and commercialization of docetaxel.
      Recently, various kinds of non-injection delivery systems for docetaxel have been
      developed to eliminate the polysorbate 80-based vehicle and increase the drug
      solubility. In this review, the non-injection delivery formulations of docetaxel
      for oral route, transdermal delivery, lung and rectal administration were
      discussed for future study and clinical application.

PMID- 24098910
TI  - Dentist-to-population and practice-to-population ratios: in a shortage
      environment with gross mal-distribution what should rural and remote communities
      focus their attention on?
AB  - INTRODUCTION: Australia is the sixth largest country (in area) in the world with
      a total area of over 7.5 million km2 (3 million miles2). To date much of the
      research and policy activity in the dental workforce has been based on simple
      statistical analysis including practitioner-to-population ratios; however, risks
      are associated with the application of these types of ratios. This study examined
      practice-to-population (PtP) ratios as a measure of accessibility. METHODS: Two
      states of Australia with a total population of about 8 million people were chosen
      for the study data frame-set. RESULTS: General dental practice (n=3841) locations
      were mapped against population for each state and each suburb (n=3545) within
      each state. Practice-to-population ratios for each suburb differed by almost
      40,000% (ranging from 1:52 to 1:20,100) with the greatest density of practices in
      the core of the capital cities - coincident with high wealth areas. CONCLUSION:
      The study found that PtP ratios in the context of workforce mal-distribution and
      geographic impediments to access is an important measure.

PMID- 24098912
TI  - Stressor-response models: a practical application for the development of lake
      nutrient criteria in China.

PMID- 24098911
TI  - Long non-coding RNA MEG3 inhibits NSCLC cells proliferation and induces apoptosis
      by affecting p53 expression.
AB  - BACKGROUND: Long non-coding RNAs play an important role in tumorigenesis, hence,
      identification of cancer-associated lncRNAs and investigation of their biological
      functions and molecular mechanisms are important for understanding the
      development and progression of cancer. Recently, the downregulation of lncRNA
      MEG3 has been observed in various human cancers. However, its role in non-small
      cell lung cancer (NSCLC) is unknown. The aim of this study was to examine the
      expression pattern of MEG3 in NSCLC and to evaluate its biological role and
      clinical significance in tumor progression. METHODS: Expression of MEG3 was
      analyzed in 44 NSCLC tissues and 7 NSCLC cell lines by qRT-PCR. Over-expression
      approaches were used to investigate the biological functions of MEG3 in NSCLC
      cells. Bisulfite sequencing was used to investigate DNA methylation on MEG3
      expression. The effect of MEG3 on proliferation was evaluated by MTT and colony
      formation assays, and cell apoptosis was evaluated by Hoechst staining and Flow
      cytometric analysis. NSCLC cells transfected with pCDNA-MEG3 were injection into
      nude mice to study the effect of MEG3 on tumorigenesis in vivo . Protein levels
      of MEG3 targets were determined by western blot analysis. Differences between
      groups were tested for significance using Student's t-test (two-tailed). RESULTS:
      MEG3 expression was decreased in non-small cell lung cancer (NSCLC) tumor tissues
      compared with normal tissues, and associated with advanced pathologic stage, and
      tumor size. Moreover, patients with lower levels of MEG3 expression had a
      relatively poor prognosis. Overexpression of MEG3 decreased NSCLC cells
      proliferation and induced apoptosis in vitro and impeded tumorigenesis in vivo.
      MDM2 and p53 protein levels were affected by MEG3 over-expression in vitro.
      CONCLUSIONS: Our findings indicate that MEG3 is significantly down-regulated in
      NSCLC tissues that could be affected by DNA methylation, and regulates NSCLC cell
      proliferation and apoptosis, partially via the activition of p53. Thus, MEG3 may
      represent a new marker of poor prognosis and is a potential therapeutic target
      for NSCLC intervention.

PMID- 24098913
TI  - Enumeration of labile hydrogens in natural organic matter by use of
      hydrogen/deuterium exchange Fourier transform ion cyclotron resonance mass
      spectrometry.
AB  - A method to enumerate labile hydrogens in all constituents of molecular ensemble
      of natural organic matter (NOM) based on our previously developed simple
      hydrogen/deuterium (H/D) exchange (electrospray ionization (ESI) ion source
      (Kostyukevich et al. Anal. Chem. 2013, 85, 5330) and ultra-high-resolution
      Fourier transform ion cyclotron resonance mass spectrometry is presented. The
      method was applied for analysis of Suwannee River fulvic acid (SRFA), which is an
      International Humic Substances Society standard, as well as Siberian crude oil;
      and lignosulfonate. We found that SRFA and lignosulfonate molecules contain 2-5
      labile hydrogens, and their number increases with the number of oxygens in the
      molecule. Also, we observed that compounds of Siberian crude oil ionizing in
      positive-ESI mode do not have labile hydrogens, while compounds ionizing in
      negative-ESI mode have one labile hydrogen that detaches during ESI ionization.

PMID- 24098914
TI  - Reactivity of chlorotrifluoromethylcarbene: activation parameters for halocarbene
      alkene addition reactions.
AB  - Activation parameters are reported for ClCCF3 additions to three alkenes
      (tetramethylethylene, cyclohexene, and 1-hexene). The results are compared to
      those for CCl2, CClF, and CF2. Activation enthalpies decrease as the carbene
      stability decreases and its electrophilicity increases, and also as alkene
      reactivity (degree of alkylation) increases. Activation entropies decrease in
      parallel with activation enthalpies, suggesting the operation of enthalpy-entropy
      compensation in these carbene additions. 

PMID- 24098915
TI  - Acute brain infarction detected by CCT and stroke risk in patients with transient
      ischemic attack lasting <1 hour.
AB  - BACKGROUND AND PURPOSE: This study aimed to determine the frequency and
      associated factors of acute brain infarction (ABI) detected by noncontrast
      cranial computed tomography (CCT) in patients with transient ischemic attack
      (TIA) of symptom duration <1 h and to investigate the association between
      evidence of ABI and short-term risk of stroke. METHODS: During a 54-month period
      (starting November 2007), consecutive patients with TIA (symptom duration <1 h)
      admitted and imaged with CCT were prospectively evaluated. Adjusted logistic
      regression was used to estimate odds ratios (ORs). RESULTS: Of 1021 patients
      (mean age, 74.5 +/- 11 years; 52% female) with TIA (symptom duration <1 h) imaged
      with CCT at admission, 68 patients (6.7%; 95% CI, 5.3-8.3%) exhibited TIA-related
      ABI. Adjusted logistic regression showed that ABI was independently correlated
      with atrial fibrillation (AF) (OR, 3.3; 95% CI, 1.4-7.9; p = 0.006) and time
      between onset and CT assessment >6 h (OR, 2.5; 95% CI, 1.1-6.1; p = 0.034).
      During hospitalization (5 +/- 3 d), 22 patients (2.2%; 95% CI, 1.4-3.1%)
      developed a stroke. Patients with ABI had higher stroke rates than those without
      (10.3% and 1.6%, respectively; p < 0.001). Adjusted logistic regression revealed
      that stroke risk was independently correlated with ABI (OR, 5.3; 95% CI, 1.8
      15.0; p = 0.002) and AF (OR, 2.6; 95% CI, 1.1-6.4; p = 0.026). CONCLUSIONS:
      Detection of ABI by CCT in TIA patients with symptom duration <1 h may depend on
      timing of CCT assessment and presence of AF. Evidence of ABI indicates an
      elevated stroke risk during hospitalization.

PMID- 24098916
TI  - Synthesis, characterization, and evaluation of a novel inhibitor of WNT/beta
      catenin signaling pathway.
AB  - BACKGROUND: Wnt/beta-catenin signaling is a highly conserved pathway in organism
      evolution and is important in many biological processes. Overactivation of
      Wnt/beta-catenin signaling is closely related to tumor development and
      progression. To identify potent small molecules that can fight aberrant Wnt/beta
      catenin-mediated cancer, we synthesized a novel pyrazoline derivative (N-(4
      hydroxybenzyl)-1,3,4-triphenyl-4,5-dihydro-1H-pyrazole-5-carboxamide, BHX) to
      block Wnt signaling, and determined the absolute configuration of its precursor
      (ethyl 1,3,4-triphenyl-4,5-dihydro-1H-pyrazole-5-carboxylate). We then evaluated
      the inhibitory effect of BHX in vitro and in vivo. RESULTS: Cell proliferation
      was assessed in three human cancer cell lines (A549, HT29, and MGC803) in the
      presence and absence of BHX using MTS assays. BHX effectively inhibited A549,
      HT29, and MGC803 cell proliferation with IC50 of 5.43 +/- 1.99, 6.95 +/- 0.24,
      and 7.62 +/- 1.31 MUM, respectively. BHX significantly induced apoptosis and G1
      phase arrest in A549 and MGC803 cells. The beta-catenin protein level was
      markedly reduced in A549 and MGC803 cells under BHX treatment. The inhibitory
      effect of BHX in vivo was investigated using a mouse xenograft model. A549
      xenograft growth was suppressed by 50.96% in nude mice treated continuously with
      100 mg/kg BHX for 21 d. Weight remained almost unchanged, which indicates the low
      toxicity of the compound. CONCLUSIONS: Our data suggest that BHX is a new drug
      candidate for cancer treatment because of its potent effect on the Wnt/beta
      catenin pathway and low toxicity.

PMID- 24098918
TI  - Editorial introduction.

PMID- 24098919
TI  - Effective visualization of integrated knowledge and data to enable informed
      decisions in drug development and translational medicine.
AB  - Integrative understanding of preclinical and clinical data is imperative to
      enable informed decisions and reduce the attrition rate during drug development.
      The volume and variety of data generated during drug development have increased
      tremendously. A new information model and visualization tool was developed to
      effectively utilize all available data and current knowledge. The Knowledge Plot
      integrates preclinical, clinical, efficacy and safety data by adding two
      concepts: knowledge from the different disciplines and protein binding.Internal
      and public available data were gathered and processed to allow flexible and
      interactive visualizations. The exposure was expressed as the unbound
      concentration of the compound and the treatment effect was normalized and scaled
      by including expert opinion on what a biologically meaningful treatment effect
      would be.The Knowledge Plot has been applied both retrospectively and
      prospectively in project teams in a number of different therapeutic areas,
      resulting in closer collaboration between multiple disciplines discussing both
      preclinical and clinical data. The Plot allows head to head comparisons of
      compounds and was used to support Candidate Drug selections and differentiation
      from comparators and competitors, back translation of clinical data,
      understanding the predictability of preclinical models and assays, reviewing
      drift in primary endpoints over the years, and evaluate or benchmark compounds in
      due diligence comparing multiple attributes.The Knowledge Plot concept allows
      flexible integration and visualization of relevant data for interpretation in
      order to enable scientific and informed decision-making in various stages of drug
      development. The concept can be used for communication, decision-making,
      knowledge management, and as a forward and back translational tool, that will
      result in an improved understanding of the competitive edge for a particular
      project or disease area portfolio. In addition, it also builds up a knowledge and
      translational continuum, which in turn will reduce the attrition rate and costs
      of clinical development by identifying poor candidates early. 

PMID- 24098920
TI  - Using behavioural theories to optimise shared haemodialysis care: a qualitative
      intervention development study of patient and professional experience.
AB  - BACKGROUND: Patients in control of their own haemodialysis report better outcomes
      than those receiving professional controlled care in a hospital setting, even
      though home and hospital haemodialysis are largely equivalent from mechanical and
      physiological perspectives. Shared Haemodialysis Care (SHC) describes an
      initiative in which hospital haemodialysis patients are supported by dialysis
      staff to become as involved as they wish in their own care; and can improve
      patient safety, satisfaction and may reduce costs. We do not understand why
      interventions to support self-management in other conditions have variable
      effects or how to optimise the delivery of SHC. The purpose of this study was to
      identify perceived patient and professional (nurses and healthcare assistants)
      barriers to the uptake of SHC, and to use these data to identify intervention
      components to optimise care. METHODS: Individual semi-structured interviews with
      patients and professionals were conducted to identify barriers and facilitators.
      Data were coded to behavioural theory to identify solutions. A national UK
      learning event with multiple stakeholders (patients, carers, commissioners and
      professionals) explored the salience of these barriers and the acceptability of
      solutions. RESULTS: A complex intervention strategy was designed to optimise SHC
      for patients and professionals. Interviews were conducted with patients (n = 15)
      and professionals (n = 7) in two hospitals and three satellite units piloting
      SHC. Data from patient and professional interviews could be coded to behavioural
      theory. Analyses identified key barriers (knowledge, beliefs about capabilities,
      skills and environmental context and resources). An intervention strategy that
      focuses on providing, first, patients with information about the shared nature of
      care, how to read prescriptions and use machines, and second, providing
      professionals with skills and protected time to teach both
      professionals/patients, as well as providing continual review, may improve the
      implementation of SHC and be acceptable to stakeholders. CONCLUSIONS: We have
      developed an intervention strategy to improve the implementation of SHC for
      patients and professionals. While this intervention strategy has been
      systematically developed using behavioural theory, it should be rigorously tested
      in a subsequent effectiveness evaluation study prior to implementation to ensure
      that shared haemodialysis care can be delivered equitably, efficiently and safely
      for all patients.

PMID- 24098921
TI  - The Conversations About Cancer (CAC) project: assessing feasibility and audience
      impacts from viewing The Cancer Play.
AB  - Basic communication research has identified a major social problem: communicating
      about cancer from diagnosis through death of a loved one. Over the past decade,
      an award-winning investigation into how family members talk through cancer on the
      telephone, based on a corpus of 61 phone calls over a period of 13 months, has
      been transformed into a theatrical production entitled The Cancer Play. All
      dialogue in the play is drawn from naturally occurring (transcribed) interactions
      between family members as they navigate their way through the trials,
      tribulations, hopes, and triumphs of a cancer journey. This dramatic performance
      explicitly acknowledges the power of the arts as an exceptional learning tool for
      extending empirical research, exploring ordinary family life, and exposing the
      often taken-for-granted conceptions of health and illness. In this study, a Phase
      I STTR project funded by the National Cancer Institute (NCI), we assess the
      feasibility of educating and impacting cancer patients, family members, and
      medical professionals who viewed the play as a live performance and through DVD
      screenings. Pre- and postperformance questionnaires were administered to solicit
      audience feedback. Pre-post change scores demonstrate overwhelming and positive
      impacts for changing opinions about the perceived importance, and attributed
      significance, of family communication in the midst of cancer. Paired-sample t
      tests were conducted on five factor-analyzed indices/indicators-two indices of
      opinions about cancer and family communication, two indices measuring the
      importance of key communication activities, and the self-efficacy indicator-and
      all factors improved significantly (<.001). Informal talkback sessions were also
      held following the viewings, and selected audience members participated in focus
      groups. Talkback and focus-group sessions generated equally strong, support
      responses. Implications of the Phase I study are being applied in Phase II, a
      currently funded effort to disseminate the play nationally and to more rigorously
      test its impact on diverse audiences. Future directions for advancing research,
      education, and training across diverse academic and health care professions are
      discussed. 

PMID- 24098922
TI  - Genetic and environmental influences on individual differences in emotion
      regulation and its relation to working memory in toddlerhood.
AB  - This is the first study to explore genetic and environmental contributions to
      individual differences in emotion regulation in toddlers, and the first to
      examine the genetic and environmental etiology underlying the association between
      emotion regulation and working memory. In a sample of 304 same-sex twin pairs
      (140 MZ, 164 DZ) at age 3, emotion regulation was assessed using the Behavior
      Rating Scale of the Bayley Scales of Infant Development (BRS; Bayley, 1993), and
      working memory was measured by the visually cued recall (VCR) task (Zelazo,
      Jacques, Burack, & Frye, 2002) and several memory tasks from the Mental Scale of
      the BSID. Based on model-fitting analyses, both emotion regulation and working
      memory were significantly influenced by genetic and nonshared environmental
      factors. Shared environmental effects were significant for working memory, but
      not for emotion regulation. Only genetic factors significantly contributed to the
      covariation between emotion regulation and working memory.

PMID- 24098923
TI  - Sadness increases distraction by auditory deviant stimuli.
AB  - Research shows that attention is ineluctably captured away from a focal visual
      task by rare and unexpected changes (deviants) in an otherwise repeated stream of
      task-irrelevant auditory distractors (standards). The fundamental cognitive
      mechanisms underlying this effect have been the object of an increasing number of
      studies but their sensitivity to mood and emotions remains relatively unexplored
      despite suggestion of greater distractibility in negative emotional contexts. In
      this study, we examined the effect of sadness, a widespread form of emotional
      distress and a symptom of many disorders, on distraction by deviant sounds.
      Participants received either a sadness induction or a neutral mood induction by
      means of a mixed procedure based on music and autobiographical recall prior to
      taking part in an auditory-visual oddball task in which they categorized visual
      digits while ignoring task-irrelevant sounds. The results showed that although
      all participants exhibited significantly longer response times in the visual
      categorization task following the presentation of rare and unexpected deviant
      sounds relative to that of the standard sound, this distraction effect was
      significantly greater in participants who had received the sadness induction (a
      twofold increase). The residual distraction on the subsequent trial (postdeviance
      distraction) was equivalent in both groups, suggesting that sadness interfered
      with the disengagement of attention from the deviant sound and back toward the
      target stimulus. We propose that this disengagement impairment reflected the
      monopolization of cognitive resources by sadness and/or associated ruminations.
      Our findings suggest that sadness can increase distraction even when distractors
      are emotionally neutral.

PMID- 24098924
TI  - Association learning for emotional harbinger cues: when do previous emotional
      associations impair and when do they facilitate subsequent learning of new
      associations?
AB  - Neutral cues that predict emotional events (emotional harbingers) acquire
      emotional properties and attract attention. Given the importance of emotional
      harbingers for future survival, it is desirable to flexibly learn new facts about
      emotional harbingers when needed. However, recent research revealed that it is
      harder to learn new associations for emotional harbingers than cues that predict
      non-emotional events (neutral harbingers). In the current study, we addressed
      whether this impaired association learning for emotional harbingers is altered by
      one's awareness of the contingencies between cues and emotional outcomes. Across
      3 studies, we found that one's awareness of the contingencies determines
      subsequent association learning of emotional harbingers. Emotional harbingers
      produced worse association learning than neutral harbingers when people were not
      aware of the contingencies between cues and emotional outcomes, but produced
      better association learning when people were aware of the contingencies. These
      results suggest that emotional harbingers do not always suffer from impaired
      association learning and can show facilitated learning depending on one's
      contingency awareness.

PMID- 24098925
TI  - The 5-HTTLPR polymorphism in the serotonin transporter gene moderates the
      association between emotional behavior and changes in marital satisfaction over
      time.
AB  - Why do some individuals become dissatisfied with their marriages when levels of
      negative emotion are high and levels of positive emotions are low, whereas others
      remain unaffected? Using data from a 13-year longitudinal study of middle-aged
      and older adults in long-term marriages, we examined whether the 5-HTTLPR
      polymorphism in the serotonin transporter gene moderates the association between
      negative and positive emotional behavior (objectively measured during marital
      conflict) and changes in marital satisfaction over time. For individuals with two
      short alleles of 5-HTTLPR, higher negative and lower positive emotional behavior
      at Time 1 predicted declines in marital satisfaction over time (even after
      controlling for depression and other covariates). For individuals with one or two
      long alleles, emotional behavior did not predict changes in marital satisfaction.
      We also found evidence for a crossover interaction (individuals with two short
      alleles of 5-HTTLPR and low levels of negative or high levels of positive emotion
      had the highest levels of marital satisfaction). These findings provide the first
      evidence of a specific genetic polymorphism that moderates the association
      between emotional behavior and changes in marital satisfaction over time and are
      consistent with increasing evidence that the short allele of this polymorphism
      serves as a susceptibility factor that amplifies sensitivity to both negative and
      positive emotional influences.

PMID- 24098927
TI  - Mindful acceptance dampens neuroaffective reactions to external and rewarding
      performance feedback.
AB  - Previous research on mindfulness has suggested that individuals high in trait
      mindfulness show heightened sensitivity to visceral and internally generated
      stimuli. However, when mindful individuals are exposed to external stimuli-such
      as pictures or faces-their emotional responses are typically attenuated. In the
      current study, we tested how trait mindfulness relates to reactivity in response
      to a different type of external stimulus, namely, performance feedback. Using
      electroencephalography, we recorded participants' neuroaffective reactions to
      rewarding, aversive, and neutral feedback, as indexed by the feedback-related
      negativity (FRN). The FRN is a brain response that peaks approximately 250 ms
      after feedback presentation, and it is thought to differentiate feedback
      indicating favorable versus unfavorable outcomes. Our findings suggest trait
      mindfulness predicts less differentiation of rewarding from neutral feedback, but
      does not predict brain differentiation of aversive from neutral feedback. This
      was the case particularly for individuals who scored highly on the "acceptance"
      facet of mindfulness, a facet that assesses the nonjudgmental acceptance of
      thoughts and emotions. We discuss the implications of these findings for current
      theory on mindfulness and emotion regulation.

PMID- 24098926
TI  - Social status and anger expression: the cultural moderation hypothesis.
AB  - Individuals with lower social status have been reported to express more anger,
      but this evidence comes mostly from Western cultures. Here, we used
      representative samples of American and Japanese adults and tested the hypothesis
      that the association between social status and anger expression depends on
      whether anger serves primarily to vent frustration, as in the United States, or
      to display authority, as in Japan. Consistent with the assumption that lower
      social standing is associated with greater frustration stemming from life
      adversities and blocked goals, Americans with lower social status expressed more
      anger, with the relationship mediated by the extent of frustration. In contrast,
      consistent with the assumption that higher social standing affords a privilege to
      display anger, Japanese with higher social status expressed more anger, with the
      relationship mediated by decision-making authority. As expected, anger expression
      was predicted by subjective social status among Americans and by objective social
      status among Japanese. Implications for the dynamic construction of anger and
      anger expression are discussed.

PMID- 24098928
TI  - Gut check: reappraisal of disgust helps explain liberal-conservative differences
      on issues of purity.
AB  - Disgust plays an important role in conservatives' moral and political judgments,
      helping to explain why conservatives and liberals differ in their attitudes on
      issues related to purity. We examined the extent to which the emotion-regulation
      strategy reappraisal drives the disgust-conservatism relationship. We
      hypothesized that disgust has less influence on the political and moral judgments
      of liberals because they tend to regulate disgust reactions through emotional
      reappraisal more than conservatives. Study 1a found that a greater tendency to
      reappraise disgust was negatively associated with conservatism, independent of
      disgust sensitivity. Study 1b replicated this finding, demonstrating that the
      effect of reappraisal is unique to disgust. In Study 2, liberals condemned a
      disgusting act less than conservatives, and did so to the extent that they
      reappraised their initial disgust response. Study 3 manipulated participants' use
      of reappraisal when exposed to a video of men kissing. Conservatives instructed
      to reappraise their emotional reactions subsequently expressed more support for
      same-sex marriage than conservatives in the control condition, demonstrating
      attitudes statistically equivalent to liberal participants.

PMID- 24098929
TI  - Interpersonal emotion regulation.
AB  - Contemporary emotion regulation research emphasizes intrapersonal processes such
      as cognitive reappraisal and expressive suppression, but people experiencing
      affect commonly choose not to go it alone. Instead, individuals often turn to
      others for help in shaping their affective lives. How and under what
      circumstances does such interpersonal regulation modulate emotional experience?
      Although scientists have examined allied phenomena such as social sharing,
      empathy, social support, and prosocial behavior for decades, there have been
      surprisingly few attempts to integrate these data into a single conceptual
      framework of interpersonal regulation. Here we propose such a framework. We first
      map a "space" differentiating classes of interpersonal regulation according to
      whether an individual uses an interpersonal regulatory episode to alter their own
      or another person's emotion. We then identify 2 types of processes--response
      dependent and response-independent--that could support interpersonal regulation.
      This framework classifies an array of processes through which interpersonal
      contact fulfills regulatory goals. More broadly, it organizes diffuse, heretofore
      independent data on "pieces" of interpersonal regulation, and identifies growth
      points for this young and exciting research domain.

PMID- 24098930
TI  - The relations of ego-resiliency and emotion socialization to the development of
      empathy and prosocial behavior across early childhood.
AB  - The present study explored early personality and environmental predictors of the
      development of young children's empathy, as well as relations of empathy to
      prosocial behavior with peers at a later age. How children manage their own
      emotions and behaviors when under stress--their ego-resiliency--would be expected
      to affect their responses to others' emotions. Also, socialization experiences,
      such as the quality of parenting behaviors, have been associated with individual
      differences in empathy-related responding. We examined whether mothers' emotion
      socialization practices and children's ego-resiliency at 18 months predicted
      initial levels and change in empathy across five time points (24, 30, 42, 48, and
      54 months; N = 242), and whether empathy in turn predicted prosocial behavior
      with peers at 72/84 months of age. Ego-resiliency and mothers' expressive
      encouragement both uniquely predicted the intercept of empathy. Boys' empathy was
      lower than girls' but improved more with age. Initial levels and growth of
      empathy positively predicted later prosocial behavior. Children's ego-resiliency
      predicted the slope of empathy at near significance (p = .054). We also found
      that the intercept of empathy mediated the relation between ego-resiliency and
      prosocial behavior as well as the relation between mothers' expressive
      encouragement and prosocial behavior. These findings suggest that both parenting
      and personality characteristics are relevant to the development of empathy during
      early childhood and might contribute to children's later prosocial behavior with
      peers.

PMID- 24098931
TI  - Intracanal placement of calcium hydroxide: a comparison of specially designed
      paste carrier technique with other techniques.
AB  - BACKGROUND: This study compared the effectiveness of a Specially Designed Paste
      Carrier technique with the Syringe-Spreader technique and the Syringe-Lentulo
      spiral technique in the intracanal placement of calcium hydroxide. METHODS: Three
      groups, each containing 15 single-rooted human anterior teeth were prepared using
      standardized Mtwo rotary instruments to a master apical file size 40 with 0.04
      taper. Each group was filled with calcium hydroxide paste using: Syringe and #25
      finger spreader (Group 1); Syringe and #4 rotary Lentulo spiral (Group 2),
      Specially Designed Paste Carrier (Group 3). Using pre-filling and post-filling
      radiographs in buccolingual and mesiodistal planes, the radiodensities at 1 mm, 3
      mm, 5 mm, and 7 mm from the apical foramen were analyzed by ANOVA and Bonferroni
      post hoc tests. RESULTS: Overall, The Specially Designed Paste Carrier technique
      showed a statistically significantly higher mean radiodensity than the two other
      compared techniques. No significant difference was detected between the Syringe
      Lentulo spiral and the Syringe-Spreader techniques. CONCLUSION: The Specially
      Designed Paste Carrier technique was more effective than the Syringe-Spreader
      technique and the Syringe-Lentulo spiral technique in the intracanal placement of
      calcium hydroxide.

PMID- 24098932
TI  - Assessing pathogenicity of Gallibacterium anatis in a natural infection model:
      the respiratory and reproductive tracts of chickens are targets for bacterial
      colonization.
AB  - Two separate bird trials were performed to establish a reliable route of
      infection for Gallibacterium anatis in chickens, comparing intranasal (i.n.) and
      intravenous (i.v.) applications. Additionally, three mutually divergent isolates
      from three geographical locations, as shown by MALDI-TOF-MS and partial rpoB gene
      sequence analysis, were compared. In the first trial, birds were infected with
      one of the selected isolates by the i.v. or i.n. route. Subsequently, birds were
      killed 3, 12 and 24 h post infection following i.v. infection while at 3, 7 and
      10 days post infection (dpi) in the case of i.n. infection along with birds of
      the control group. As a result, i.n. infection showed prominent and consistent
      bacterial tissue distribution in different organs persisting until 10 dpi, which
      was a striking contrast to the i.v. infection route. Likewise, histopathology
      revealed mild to severe tracheal lesions following i.n. infection. The second
      trial was set up to confirm both the achieved results and the robustness of i.n.
      infection but with an extended observation period, until 28 dpi In agreement with
      the preceding trial, identical results for bacteriological and histopathological
      examinations were obtained with persistency of bacteria until 28 dpi Comparing
      the three different isolates from Mexico, China and Austria, the Mexican isolate
      showed a somewhat higher pathogenicity than the other strains. Consequently,
      pathogenesis of G. anatis strains was studied in chickens elucidating i.n.
      infection as the most reliable route characterized by a long-lasting bacteraemia,
      targeting the respiratory and reproductive tract. 

PMID- 24098933
TI  - Antiflammin-1 attenuates bleomycin-induced pulmonary fibrosis in mice.
AB  - BACKGROUND: Antiflammin-1 (AF-1), a derivative of uteroglobin (UG), is a
      synthetic nonapeptide with diverse biological functions. In the present study, we
      investigated whether AF-1 has a protective effect against bleomycin-induced
      pulmonary fibrosis. METHODS: C57BL/6 mice were injected with bleomycin
      intratracheally to create an animal model of bleomycin-induced pulmonary
      fibrosis. On Day 7 and Day 28, we examined the anti-inflammatory effect and
      antifibrotic effect, respectively, of AF-1 on the bleomycin-treated mice. The
      effects of AF-1 on the transforming growth factor-beta 1 (TGF-beta1)-induced
      proliferation of murine lung fibroblasts (NIH3T3) were examined by a
      bromodeoxycytidine (BrdU) incorporation assay and cell cycle analysis. RESULTS:
      Severe lung inflammation and fibrosis were observed in the bleomycin-treated mice
      on Day 7 and Day 28, respectively. Administration of AF-1 significantly reduced
      the number of neutrophils in the bronchoalveolar lavage fluid (BALF) and the
      levels of tumor necrosis factor-alpha (TNF-alpha) and interleukin-1 beta (IL
      1beta) in the lung homogenates on Day 7. Histological examination revealed that
      AF-1 markedly reduced the number of infiltrating cells on Day 7 and attenuated
      the collagen deposition and destruction of lung architecture on Day 28. The
      hydroxyproline (HYP) content was significantly decreased in the AF-1-treated
      mice. In vitro, AF-1 inhibited the TGF-beta1-induced proliferation of NIH3T3
      cells, which was mediated by the UG receptor. CONCLUSIONS: AF-1 has anti
      inflammatory and antifibrotic actions in bleomycin-induced lung injury. We
      propose that the antifibrotic effect of AF-1 might be related to its suppression
      of fibroblast growth in bleomycin-treated lungs and that AF-1 has potential as a
      new therapeutic tool for pulmonary fibrosis.

PMID- 24098934
TI  - Cytosine methylation changes in enhancer regions of core pro-fibrotic genes
      characterize kidney fibrosis development.
AB  - BACKGROUND: One in eleven people is affected by chronic kidney disease, a
      condition characterized by kidney fibrosis and progressive loss of kidney
      function. Epidemiological studies indicate that adverse intrauterine and
      postnatal environments have a long-lasting role in chronic kidney disease
      development. Epigenetic information represents a plausible carrier for mediating
      this programming effect. Here we demonstrate that genome-wide cytosine
      methylation patterns of healthy and chronic kidney disease tubule samples
      obtained from patients show significant differences. RESULTS: We identify
      differentially methylated regions and validate these in a large replication
      dataset. The differentially methylated regions are rarely observed on promoters,
      but mostly overlap with putative enhancer regions, and they are enriched in
      consensus binding sequences for important renal transcription factors. This
      indicates their importance in gene expression regulation. A core set of genes
      that are known to be related to kidney fibrosis, including genes encoding
      collagens, show cytosine methylation changes correlating with downstream
      transcript levels. CONCLUSIONS: Our report raises the possibility that epigenetic
      dysregulation plays a role in chronic kidney disease development via influencing
      core pro-fibrotic pathways and can aid the development of novel biomarkers and
      future therapeutics.

PMID- 24098935
TI  - BMAALS: a French national project searching for a link between amyotrophic
      lateral sclerosis and the neurotoxic amino acid L-BMAA.

PMID- 24098936
TI  - Mosaic pregnancy after transfer of a "euploid" blastocyst screened by DNA
      microarray.
AB  - BACKGROUND: High proportions of human embryos produced by in vitro fertilization
      are aneuploidy and mosaic. DNA microarray is one of the most practical screening
      methods to select euploid embryos for transfer. However, mosaic pregnancy is
      still possible due to embryonic mosacism. Here we report a successful pregnancy
      after transfer of a mosaic blastocyst with euploid inner cell mass. METHODS: A
      woman with a previous trisomy 13 pregnancy pursued infertility treatment with
      preimplantation genetic screening by a trophectoderm biopsy and DNA microarray.
      NimbleGen oligonucleotide DNA microarray was applied to biopsied samples from 13
      blastocysts. A euploid blastocyst was transferred to the patient and subsequent
      prenatal cytogenetic tests were performed by FISH and/or G banding. RESULTS:
      Following DNA microarray, it was found that 5 blastocysts were euploid and 8 were
      aneuploidy. Transfer of one euploid blastocyst resulted in a clinical pregnancy.
      Prenatal cytogenetic tests of samples biopsied from chorionic villi sample showed
      both trisomy 21 (47 XX, +21) and euploid (46, XX) cells. Further prenatal
      cytogenetic test with a sample from amniotic fluid indicated that all cells were
      euploid (46, XX). The pregnancy was continued and a healthy girl was delivered
      after 41 weeks of gestation. CONCLUSIONS: This is the first report to indicate a
      mosaic pregnancy after transfer of a "euploid" blastocyst that was screened by
      DNA microarray, and the case further confirms that mosaicism is present in human
      blastocysts produced by in vitro fertilization.

PMID- 24098938
TI  - The T-box transcription factor, TBX3, is sufficient to promote melanoma formation
      and invasion.
AB  - The T-box transcription factor, TBX3, is overexpressed in several cancers and has
      been proposed as a chemotherapeutic target. Several lines of evidence suggest
      that TBX3 may be a key contributor to malignant melanoma, a highly aggressive and
      intractable disease. Using in vitro and in vivo assays we demonstrate here for
      the first time that overexpressing TBX3 in non-tumourigenic early stage melanoma
      cells is sufficient to promote tumour formation and invasion. Furthermore, we
      show that TBX3 may play an important role as a reciprocal switch between
      substrate dependent cell proliferation and tumour invasion. 

PMID- 24098937
TI  - Metallothionein 1G functions as a tumor suppressor in thyroid cancer through
      modulating the PI3K/Akt signaling pathway.
AB  - BACKGROUND: MT1G inactivation mediated by promoter methylation has been reported
      in thyroid cancer. However, the role of MT1G in thyroid carcinogenesis remains
      unclear. The aim of this study is to examine the biological functions and related
      molecular mechanisms of MT1G in thyroid cancer. METHODS: Methylation-specific PCR
      (MSP) was performed to analyze promoter methylation of MT1G and its relationship
      with clinicopathological characteristics of papillary thyroid cancer (PTC)
      patients. Conventional and real-time quantitative RT-PCR assays were used to
      evaluate mRNA expression. The functions of ectopic MT1G expression were
      determined by cell proliferation and colony formation, cell cycle and apoptosis,
      as well as cell migration and invasion assays. RESULTS: MT1G expression was
      frequently silenced or down-regulated in thyroid cancer cell lines, and was also
      significantly decreased in primary thyroid cancer tissues compared with non
      malignant thyroid tissues. Promoter methylation, along with histone modification,
      contributes to MT1G inactivation in thyroid tumorigenesis. Moreover, our data
      showed that MT1G hypermethylation was significantly positively associated with
      lymph node metastasis in PTC patients. Importantly, restoring MT1G expression in
      thyroid cancer cells dramatically suppressed cell growth and invasiveness, and
      induced cell cycle arrest and apoptosis through inhibiting phosphorylation of Akt
      and Rb. CONCLUSIONS: We have for the first time revealed that MT1G appears to be
      functional tumor suppressor involved in thyroid carcinogenesis mainly through
      modulating the phosphatidylinositol-3-kinase (PI3K)/Akt pathway and partially
      through regulating the activity of Rb/E2F pathway in this study.

PMID- 24098939
TI  - Notch signaling activation contributes to cardioprotection provided by ischemic
      preconditioning and postconditioning.
AB  - BACKGROUND: Notch signaling is known to be activated following myocardial
      ischemia, but its role in cardioprotection provided by ischemic preconditioning
      (IPC) and ischemic postconditioning (IPost) remains unclear. METHODS: Lentiviral
      vectors were constructed to overexpress or knockdown N1ICD in H9c2 cardiomyocyte
      and rat heart exposed to ischemia reperfusion injury (IRI), IPC or IPost.
      RESULTS: Notch1 signaling was activated during myocardial IPC and IPost, and
      could enhance cell viability and inhibit apoptosis. Furthermore, activated Notch1
      signaling stabilized mitochondrial membrane potential and reduced reactive oxygen
      species induced by IRI. The cardioprotection provided by activated Notch1
      signaling resembled that of IPC and IPost, which was related to Stat3 activation
      and regulation of apoptosis related proteins. Furthermore, in langendorff heart
      perfusion model, activated Notch1 signaling restored cardiac function, decreased
      lactate dehydrogenase release and limited infarct size after myocardial ischemia.
      CONCLUSIONS: Notch1 signaling is activated and mediates cardioprotection provided
      by IPC and Ipost. Notch1 signaling may represent a potential new pharmacologic
      mimic for cardioprotection of ischemic heart disease.

PMID- 24098940
TI  - Evaluating the effectiveness of a multifaceted, multilevel continuous quality
      improvement program in primary health care: developing a realist theory of
      change.
AB  - BACKGROUND: Variation in effectiveness of continuous quality improvement (CQI)
      interventions between services is commonly reported, but with little explanation
      of how contextual and other factors may interact to produce this variation.
      Therefore, there is scant information available on which policy makers can draw
      to inform effective implementation in different settings. In this paper, we
      explore how patterns of change in delivery of services may have been achieved in
      a diverse range of health centers participating in a wide-scale program to
      achieve improvements in quality of care for Indigenous Australians. METHODS: We
      elicited key informants' interpretations of factors explaining patterns of change
      in delivery of guideline-scheduled services over three or more years of a wide
      scale CQI project, and inductively analyzed these interpretations to propose fine
      grained realist hypotheses about what works for whom and in what circumstances.
      Data were derived from annual clinical audits from 36 health centers operating in
      diverse settings, quarterly project monitoring reports, and workshops with 12 key
      informants who had key roles in project implementation. We abstracted potential
      context-mechanism-outcome configurations from the data, and based on these,
      identified potential program-strengthening strategies. RESULTS: Several context
      specific, mechanism-based explanations for effectiveness of this CQI project were
      identified. These were collective valuing of clinical data for improvement
      purposes; collective efficacy; and organizational change towards a population
      health orientation. Health centers with strong central management of CQI, and
      those in which CQI efforts were more dependent on local health center initiative
      and were adapted to resonate with local priorities were both favorable contexts
      for collective valuing of clinical data. Where health centers had prior positive
      experiences of collaboration, effects appeared to be achieved at least partly
      through the mechanism of collective efficacy. Strong community linkages, staff
      ability to identify with patients, and staff having the skills and support to
      take broad ranging action, were favorable contexts for the mechanism of increased
      population health orientation. CONCLUSIONS: Our study provides evidence to
      support strategies for program strengthening described in the literature, and
      extends the understanding of mechanisms through which strategies may be effective
      in achieving particular outcomes in different contexts.

PMID- 24098941
TI  - 'My dreams are shuttered down and it hurts lots'-a qualitative study of
      palliative care needs and their management by HIV outpatient services in Kenya
      and Uganda.
AB  - BACKGROUND: Despite the huge burden of HIV in sub-Saharan Africa, there is little
      evidence of the multidimensional needs of patients with HIV infection to inform
      the person-centred care across physical, psychological, social and spiritual
      domains stipulated in policy guidance. We aimed to describe the problems
      experienced by people with HIV in Kenya and Uganda and the management of these
      problems by HIV outpatient services. METHODS: Local researchers conducted in
      depth qualitative interviews with HIV patients, caregivers and service staff at
      12 HIV outpatient facilities (6 in Kenya, 6 in Uganda). Interview data were
      analysed thematically. RESULTS: 189 people were interviewed (83 patients, 47
      caregivers, 59 staff). The impact of pain and symptoms and their causes (HIV,
      comorbidities, treatment side-effects) were described. Staff reported that
      effective pain relief was not always available, particularly in Kenya.
      Psychosocial distress (isolation, loneliness, worry) was exacerbated by stigma
      and poverty, and detrimentally affected adherence. Illness led to despair and
      hopelessness. Provision of counselling was reported, but spiritual support
      appeared to be less common. Neither pain nor psychosocial problems were routinely
      reported to service staff. Collaboration with local hospices and income
      generation activities for patients were highlighted as useful. CONCLUSIONS: The
      findings demonstrate the multiple and interrelated problems associated with
      living with HIV and how psychosocial and spiritual distress can contribute to
      'total pain' in this population. In line with the palliative care approach, HIV
      care requires holistic care and assessment that take into account psychological,
      socioeconomic and spiritual distress alongside improved access to pain-relieving
      drugs, including opioids.

PMID- 24098942
TI  - High-efficiency RNA cloning enables accurate quantification of miRNA expression
      by deep sequencing.
AB  - Small RNA cloning and sequencing is uniquely positioned as a genome-wide approach
      to quantify miRNAs with single-nucleotide resolution. However, significant biases
      introduced by RNA ligation in current protocols lead to inaccurate miRNA
      quantification by 1000-fold. Here we report an RNA cloning method that achieves
      over 95% efficiency for both 5' and 3' ligations. It achieves accurate
      quantification of synthetic miRNAs with less than two-fold deviation from the
      anticipated value and over a dynamic range of four orders of magnitude. Taken
      together, this high-efficiency RNA cloning method permits accurate genome-wide
      miRNA profiling from total RNAs.

PMID- 24098943
TI  - Advances in the REDCAT software package.
AB  - BACKGROUND: Residual Dipolar Couplings (RDCs) have emerged in the past two
      decades as an informative source of experimental restraints for the study of
      structure and dynamics of biological macromolecules and complexes. The REDCAT
      software package was previously introduced for the analysis of molecular
      structures using RDC data. Here we report additional features that have been
      included in this software package in order to expand the scope of its analyses.
      We first discuss the features that enhance REDCATs user-friendly nature, such as
      the integration of a number of analyses into one single operation and enabling
      convenient examination of a structural ensemble in order to identify the most
      suitable structure. We then describe the new features which expand the scope of
      RDC analyses, performing exercises that utilize both synthetic and experimental
      data to illustrate and evaluate different features with regard to structure
      refinement and structure validation. RESULTS: We establish the seamless
      interaction that takes place between REDCAT, VMD, and Xplor-NIH in demonstrations
      that utilize our newly developed REDCAT-VMD and XplorGUI interfaces. These
      modules enable visualization of RDC analysis results on the molecular structure
      displayed in VMD and refinement of structures with Xplor-NIH, respectively. We
      also highlight REDCAT's Error-Analysis feature in reporting the localized fitness
      of a structure to RDC data, which provides a more effective means of recognizing
      local structural anomalies. This allows for structurally sound regions of a
      molecule to be identified, and for any refinement efforts to be focused solely on
      locally distorted regions. CONCLUSIONS: The newly engineered REDCAT software
      package, which is available for download via the WWW from
      http://ifestos.cse.sc.edu, has been developed in the Object Oriented C++
      environment. Our most recent enhancements to REDCAT serve to provide a more
      complete RDC analysis suite, while also accommodating a more user-friendly
      experience, and will be of great interest to the community of researchers and
      developers since it hides the complications of software development.

PMID- 24098944
TI  - Comparison of diffusion-weighted with T2-weighted imaging for detection of edema
      in acute myocardial infarction.
AB  - BACKGROUND: Recent studies, performed with the use of a commercially available
      diffusion weighted imaging (DWI) sequence, showed that they are sensitive to the
      increase of water content in the myocardium and may be used as an alternative to
      the standard T2-weighted sequences. The aim of this study was to compare two
      methods of myocardial edema imaging: DWI and T2-TIRM. METHODS: The study included
      91 acute and post STEMI patients. We applied a qualitative and quantitative image
      analysis. The qualitative analysis consisted of evaluation of the quality of
      blood suppression, presence of artifacts and occurrence of high signal (edema)
      areas. On the basis of edema detection in AMI and control (post STEMI) group, the
      sensitivity and specificity of TIRM and DWI were determined. Two contrast to
      noise ratios (CNR) were calculated: CNR1--the contrast between edema and healthy
      myocardium and CNR2--the contrast between edema and intraventricular blood pool.
      The area of edema was measured for both TIRM and DWI sequences and compared with
      the infarct size in LGE images. RESULTS: Edema occurred more frequently in the
      DWI sequence. A major difference was observed in the inferior wall, where an
      edema-high signal was observed in 46% in T2-TIRM, whereas in the DWI sequence in
      85%. An analysis of the image quality parameters showed that the use of DWI
      sequence allows complete blood signal suppression in the left ventricular cavity
      and reduces the occurrence of motion artifacts. However, it is connected with a
      higher incidence of magnetic susceptibility artifacts and image distortion. An
      analysis of the CNRs showed that CNR1 in T2-TIRM sequence depends on the infarct
      location and has the lowest value for the inferior wall. The area of edema
      measured on DWI images was significantly larger than in T2-TIRM. CONCLUSIONS: DWI
      is a new technique for edema detection in patients with acute myocardial
      infarction which may be recommended for the diagnosis of acute injuries,
      especially in patients with slow-flow artifacts in TIRM images.

PMID- 24098945
TI  - Dynamic aphasia following low-grade glioma surgery near the supplementary motor
      area: a selective spontaneous speech deficit.
AB  - We describe a patient (KO) with reduced spontaneous speech, resembling dynamic
      aphasia, after awake glioma surgery in the proximity of the supplementary motor
      area. Naming, repetition, and comprehension were intact. He was tested with an
      extensive neuropsychological test-battery and a protocol for dynamic aphasia at 1
      year. He presented with postoperative reduced spontaneous speech and selective
      executive function deficits. Most language recovery took place at 3 months
      postoperatively, whereas the executive functions improved between 3 months and 1
      year. Results suggest that resection near the supplementary motor area could
      increase the risk of cognitive disturbances at long term, especially language. 

PMID- 24098946
TI  - Hankasson study on GBS intrapartum.

PMID- 24098947
TI  - RKIP phosphorylation and STAT3 activation is inhibited by oxaliplatin and
      camptothecin and are associated with poor prognosis in stage II colon cancer
      patients.
AB  - BACKGROUND: A major obstacle in treating colorectal cancer (CRC) is the acquired
      resistance to chemotherapeutic agents. An important protein in the regulation of
      cancer cell death and clinical outcome is Raf kinase inhibitor protein (RKIP). In
      contrast, activated signal transducer and activator of transcription 3 (STAT3) is
      a protein that promotes tumor cell survival by inhibiting apoptosis and has an
      important role in cancer progression in many of cancer types. The aim of this
      study was to evaluate the regulation of RKIP and STAT3 after treatment with
      clinically relevant chemotherapeutic agents (camptothecin (CPT) and oxaliplatin
      (OXP)) and the cytokine interleukin-6 (IL-6) in HCT116 colon cancer cells as well
      as evaluate the association between RKIP and STAT3 with clinical outcome of Stage
      II colon cancer patients. METHODS: HCT-116 colon cancer cells were treated with
      CPT, OXP, and IL-6 separately or in combination in a time and dose-dependent
      manner and examined for phosphorylated and non-phosphorylated RKIP and STAT3 via
      Western blot analysis. STAT3 transcriptional activity was measured via a
      luciferase reporter assay in HCT116 cells treated with CPT, IL-6 or transfected
      with JAK 1, 2 separately or in combination. We extended these observations and
      determined STAT3 and RKIP/ pRKIP in tumor microarrays (TMA) in stage II colon
      cancer patients. RESULTS: We demonstrate IL-6-mediated activation of STAT3 occurs
      in conjunction with the phosphorylation of RKIP in vitro in human colon cancer
      cells. OXP and CPT block IL-6 mediated STAT3 activation and RKIP phosphorylation
      via the inhibition of the interaction of STAT3 with gp130. We determined that
      STAT3 and nuclear pRKIP are significantly associated with poor patient prognosis
      in stage II colon cancer patients. CONCLUSIONS: In the analysis of tumor samples
      from stage II colon cancer patients and the human colon carcinoma cell line
      HCT116, pRKIP and STAT3, 2 proteins potentially involved in the resistance to
      conventional treatments were detected. The phosphorylation of pRKIP and STAT3 are
      induced by the cytokine IL-6 and suppressed by the chemotherapeutic drugs CPT and
      OXP. Therefore, these results suggest that STAT3 and pRKIP may serve as
      prognostic biomarkers in stage II colon cancer patients and may improve
      chemotherapy.

PMID- 24098948
TI  - Effects of platelet-poor plasma, platelet-rich plasma, and platelet-rich fibrin
      on healing of extraction sockets with buccal dehiscence in dogs.
AB  - Alveolar bone resorption generally occurs during healing after tooth extraction.
      This study aimed to evaluate the effects of platelet-poor plasma (PPP), platelet
      rich plasma (PRP), and platelet-rich fibrin (PRF) on healing in a ridge
      augmentation model of the canine socket with dehiscence of the buccal wall. The
      third mandibular premolars of 12 beagle dogs were extracted and a 3 mm buccal
      dehiscence from the alveolar crest to the buccal wall of the extraction socket
      was created. These sockets were then divided into four groups on the basis of the
      material used to fill the sockets: PPP, PRP, PRF, and control (no graft material)
      groups. Results were evaluated at 4 and 8 weeks after surgery. The
      ultrastructural morphology and constructs of each blood product were studied by a
      scanning electron microscope (SEM) or calculating concentrations of platelets,
      fibrinogen, platelet-derived growth factor, and transforming growth factor-beta.
      A total of five microcomputed tomography images of specimens were selected for
      measurement, and the area occupied by the newly formed bone as well as the
      horizontal bone width were measured. Moreover, decalcified tissue specimens from
      each defect were analyzed histologically. The median area of new bone at 4 and 8
      weeks and median horizontal bone width at 8 weeks were the highest in the PPP
      group. However, bone maturation in the PRF and the PRP groups was more progressed
      than that in the PPP and control groups. By SEM findings, the PRF group showed a
      more highly condensed fibrin fiber network that was regularly arranged when
      compared with the PPP and PRP groups. The growth factors released from platelets
      in PRP indicated higher concentrations than that in PRF. Under more severe
      conditions for bone formation, as in this experiment, the growth factors released
      from platelets had a negative effect on bone formation. This study showed that
      PPP is an effective material for the preservation of sockets with buccal
      dehiscence.

PMID- 24098950
TI  - An improved radiolabelled RNA aptamer molecule for HER2 imaging in cancers.
AB  - Human epidermal growth factor receptor 2 (HER2) expression has been shown to be
      increased in several types of human tumours. In this study, for the imaging of
      HER2-related tumours, a modified RNA aptamer with HER2-specific targeting was
      labelled with (99m)Tc, by using hydrazino nicotinamide (HYNIC) as the chelator in
      the presence of tricine or ethylenediamine-N,N'-diacetic acid (EDDA) as the co
      ligand. Stability testing of the radiolabelled aptamers in the serum was
      performed through SDS-PAGE. The aptamer-radionuclide conjugate was evaluated for
      its cellular HER2-specific binding in ovarian cancer cells (SKOV-3), and its
      biodistribution properties were assessed in normal and SKOV-3 tumour-bearing
      mice. In the presence of either tricine or EDDA, the HYNIC-RNA aptamers were
      labelled with (99m)Tc at a high yield and radiochemical purity. Cellular
      experiments confirmed the specific binding of the RNA aptamer to the HER2
      receptor. In the animal biodistribution study, uptake of the EDDA-co-liganded
      (99m)Tc-HYNIC-RNA aptamer by the liver and spleen was remarkably lower than that
      of the aptamer with tricine. Tumours also showed a higher accumulation of
      radioactivity with the EDDA-co-liganded aptamer complex. This study demonstrated
      EDDA to be better than tricine for use as a co-ligand with the RNA aptamer, which
      can be a potential tool for the molecular imaging of HER2-overexpressing cancers.

PMID- 24098951
TI  - Vaccination-challenge interval markedly influences protection provided by Rispens
      CVI988 vaccine against very virulent Marek's disease virus challenge.
AB  - The Rispens (CVI988) vaccine is widely used to vaccinate chickens worldwide. We
      tested the protective effects of the Rispens vaccine against challenge with very
      virulent Marek's disease virus (vvMDV) at various intervals at, before or after
      vaccination. The experiment used commercial ISA Brown layers and vvMDV isolate
      02LAR. The protective index (PI) was measured for vaccination challenge intervals
      (VCI) of -10, -5, 0, 5 and 10 days, with the negative values indicating challenge
      prior to vaccination. Chickens were challenged by injection with 400 plaque
      forming units (PFU) of 02LAR and/or vaccinated with 3200 PFU of the Rispens
      vaccine virus at days 0, 5 and 10 of age, with appropriate negative controls
      injected with diluent only. The presence of visible Marek's disease tumours was
      assessed up to 56 days post challenge. MDV challenge in unvaccinated chickens
      resulted in tumours in 52% of chickens. The Rispens vaccine provided no
      significant protection when challenge preceded vaccination, with PIs of -4 and
      21% for VCI of -5 and -10 days respectively. On the other hand, it provided PIs
      of 60, 85 and 100% at VCI of 0, 5 and 10 days respectively. The study also
      revealed that the vvMDV load in peripheral blood lymphocytes or feather tips at
      14 and 21 days post infection as determined by quantitative real-time polymerase
      chain reaction, which can distinguish pathogenic MDV from the Rispens vaccine
      strain, was an accurate early predictor of Marek's disease incidence at 56 days
      post challenge. The load of Rispens virus in peripheral blood lymphocytes or
      feathers at the same times post vaccination did not offer similar predictive
      power. 

PMID- 24098949
TI  - Ursolic and oleanolic acids as antimicrobial and immunomodulatory compounds for
      tuberculosis treatment.
AB  - BACKGROUND: New alternatives for the treatment of Tuberculosis (TB) are urgently
      needed and medicinal plants represent a potential option. Chamaedora tepejilote
      and Lantana hispida are medicinal plants from Mexico and their hexanic extracts
      have shown antimycobacterial activity. Bioguided investigation of these extracts
      showed that the active compounds were ursolic acid (UA) and oleanolic acid (OA).
      METHODS: The activity of UA and OA against Mycobacterium tuberculosis H37Rv, four
      monoresistant strains, and two drug-resistant clinical isolates were determined
      by MABA test. The intracellular activity of UA and OA against M. tuberculosis
      H37Rv and a MDR clinical isolate were evaluated in a macrophage cell line.
      Finally, the antitubercular activity of UA and OA was tested in BALB/c mice
      infected with M. tuberculosis H37Rv or a MDR strain, by determining pulmonary
      bacilli loads, tissue damage by automated histomorphometry, and expression of IFN
      gamma, TNF-alpha, and iNOS by quantitative RT-PCR. RESULTS: The in vitro assay
      showed that the UA/OA mixture has synergistic activity. The intracellular
      activity of these compounds against M. tuberculosis H37Rv and a MDR clinical
      isolate in a macrophage cell line showed that both compounds, alone and in
      combination, were active against intracellular mycobacteria even at low doses.
      Moreover, when both compounds were used to treat BALB/c mice with TB induced by
      H37Rv or MDR bacilli, a significant reduction of bacterial loads and pneumonia
      were observed compared to the control. Interestingly, animals treated with UA and
      OA showed a higher expression of IFN-gamma and TNF-alpha in their lungs, than
      control animals. CONCLUSION: UA and OA showed antimicrobial activity plus an
      immune-stimulatory effect that permitted the control of experimental pulmonary
      TB.

PMID- 24098952
TI  - Fahr's syndrome: literature review of current evidence.
AB  - Fahr's disease or Fahr's syndrome is a rare, neurological disorder characterized
      by abnormal calcified deposits in basal ganglia and cerebral cortex. Calcified
      deposits are made up of calcium carbonate and calcium phosphate, and are commonly
      located in the Basal Ganglia, Thalamus, Hippocampus, Cerebral cortex, Cerebellar
      Subcortical white matter and Dentate Nucleus. Molecular genetics of this disease
      haven't been studied extensively; hence evidence at the molecular and genetic
      level is limited. Fahr's disease commonly affects young to middle aged adults.
      Etiology of this syndrome does not identify a specific agent but associations
      with a number of conditions have been noted; most common of which are endocrine
      disorders, mitochondrial myopathies, dermatological abnormalities and infectious
      diseases. Clinical manifestations of this disease incorporate a wide variety of
      symptoms, ranging from neurological symptoms of extrapyramidal system to
      neuropsychiatric abnormalities of memory and concentration to movement disorders
      including Parkinsonism, chorea and tremors amongst others. Diagnostic criteria
      for this disease has been formulated after modifications from previous evidence
      and can be stated briefly, it consist of bilateral calcification of basal
      ganglia, progressive neurologic dysfunction, absence of biochemical
      abnormalities, absence of an infectious, traumatic or toxic cause and a
      significant family history. Imaging modalities for the diagnosis include CT, MRI,
      and plain radiography of skull. Other investigations include blood and urine
      testing for hematologic and biochemical indices. Disease is as yet incurable but
      management and treatment strategies mainly focus on symptomatic relief and
      eradication of causative factors; however certain evidence is present to suggest
      that early diagnosis and treatment can reverse the calcification process leading
      to complete recovery of mental functions. Families with a known history of Fahr's
      disease should be counseled prior to conception so that the birth of affected
      babies can be prevented. This review was written with the aim to remark on the
      current substantial evidence surrounding this disease. 

PMID- 24098953
TI  - Are IgM-enriched immunoglobulins an effective adjuvant in septic VLBW infants?
AB  - AIM: To investigate the effectiveness of IgM-enriched immunoglobulins (IgM-eIVIG)
      in reducing short-term mortality of neonates with proven late-onset sepsis.
      METHODS: All VLBW infants from January 2008 to December 2012 with positive blood
      culture beyond 72 hours of life were enrolled in a retrospective cohort study.
      Newborns born after June 2010 were treated with IgM-eIVIG, 250 mg/kg/day iv for
      three days in addition to standard antibiotic regimen and compared to an
      historical cohort born before June 2010, receiving antimicrobial regimen alone.
      Short-term mortality (i.e. death within 7 and 21 days from treatment) was the
      primary outcome. Secondary outcomes were: total mortality, intraventricular
      hemorrhage, necrotizing enterocolitis, periventricular leukomalacia,
      bronchopulmonary dysplasia at discharge. RESULTS: 79 neonates (40 cases) were
      enrolled. No difference in birth weight, gestational age or SNAP II score
      (disease severity score) were found. Significantly reduced short-term mortality
      was found in treated infants (22% vs 46%; p = 0.005) considering all microbial
      aetiologies and the subgroup affected by Candida spp. Secondary outcomes were not
      different between groups. CONCLUSION: This hypothesis-generator study shows that
      IgM-eIVIG is an effective adjuvant therapy in VLBW infants with proven sepsis.
      Randomized controlled trials are warranted to confirm this pilot observation.

PMID- 24098954
TI  - Design, synthesis, and activity of a series of arylpyrid-3-ylmethanones as type I
      positive allosteric modulators of alpha7 nicotinic acetylcholine receptors.
AB  - A series of novel arylpyrid-3-ylmethanones (7a-aa) were designed as modulators of
      alpha7 nicotinic acetylcholine receptors (nAChRs). The methanones were found to
      be type I positive allosteric modulators (PAMs) of human alpha7 nAChRs expressed
      in Xenopus ooctyes. Structure-activity relationship (SAR) studies resulted in the
      identification of compound 7v as a potent and efficacious type I PAM with maximum
      modulation of a nicotine EC5 response of 1200% and EC50 = 0.18 MUM. Compound 7z
      was active in reversing the effect of scopolamine in the novel object recognition
      (NOR) paradigm with a minimum effective ip dose of 1.0 mg/kg (2.7 MUmol/kg). This
      effect was blocked by the selective alpha7 nAChR antagonist methyllycaconitine
      (MLA). These compounds are potent type I positive allosteric modulators of alpha7
      nAChRs that may have therapeutic value in restoring impaired sensory gating and
      cognitive deficits in schizophrenia and Alzheimer's disease. 

PMID- 24098956
TI  - Effective processing of pulse field gradient NMR of mixtures by blind source
      separation.
AB  - NMR diffusometry and its flagship layout, diffusion-ordered spectroscopy (DOSY),
      are versatile for studying mixtures of bioorganic and synthetic molecules, but a
      limiting factor of its applicability is the requirement of a mathematical
      treatment capable of distinguishing molecules with similar spectra or diffusion
      constants. We present here a processing strategy for DOSY, a synergy of two high
      performance blind source separation (BSS) techniques: non-negative matrix
      factorization (NMF) using additional sparse conditioning (SC), and the JADE
      (joint approximate diagonalization of eigenmatrices) declination of independent
      component analysis (ICA). While the first approach has an intrinsic affinity for
      NMR data, the latter one can be orders of magnitude computationally faster and
      can be used to simplify the parametrization of the former. 

PMID- 24098955
TI  - A fish protein hydrolysate alters fatty acid composition in liver and adipose
      tissue and increases plasma carnitine levels in a mouse model of chronic
      inflammation.
AB  - BACKGROUND: There is growing evidence that fish protein hydrolysate (FPH) diets
      affect mitochondrial fatty acid metabolism in animals. The aim of the study was
      to determine if FPH could influence fatty acid metabolism and inflammation in
      transgene mice expressing human tumor necrosis factor alpha (hTNFalpha). METHODS:
      hTNFalpha mice (C57BL/6 hTNFalpha) were given a high-fat (23%, w/w) diet
      containing 20% casein (control group) or 15% FPH and 5% casein (FPH group) for
      two weeks. After an overnight fast, blood, adipose tissue, and liver samples were
      collected. Gene expression and enzyme activity was analysed in liver, fatty acid
      composition was analyzed in liver and ovarian white adipose tissue, and
      inflammatory parameters, carnitine, and acylcarnitines were analyzed in plasma.
      RESULTS: The n-3/n-6 fatty acid ratio was higher in mice fed the FPH diet than in
      mice fed the control diet in both adipose tissue and liver, and the FPH diet
      affected the gene expression of ?6 and ?9 desaturases. Mice fed this diet also
      demonstrated lower hepatic activity of fatty acid synthase. Concomitantly, a
      lower plasma INF-gamma level was observed. Plasma carnitine and the carnitine
      precursor gamma-butyrobetaine was higher in the FPH-group compared to control, as
      was plasma short-chained and medium-chained acylcarnitine esters. The higher
      level of plasma acetylcarnitine may reflect a stimulated mitochondrial and
      peroxisomal beta-oxidation of fatty acids, as the hepatic activities of
      peroxisomal acyl-CoA oxidase 1 and mitochondrial carnitine palmitoyltransferase
      II were higher in the FPH-fed mice. CONCLUSIONS: The FPH diet was shown to
      influence hepatic fatty acid metabolism and fatty acid composition. This
      indicates that effects on fatty acid metabolism are important for the bioactivity
      of protein hydrolysates of marine origin.

PMID- 24098957
TI  - Triterpene saponins from the aerial parts of Trifolium medium L. var. sarosiense.
AB  - Seven previously unreported triterpene glycosides (1-7) were isolated from
      methanol extract of the aerial parts of Trifolium medium var. sarosiense (zigzag
      clover). Their structures were established by the extensive use of 1D and 2D NMR
      experiments along with ESI-MS and HRMS analyses. Compounds 1-7 are oleanane
      derivatives characterized by the presence of a keto group at C-22 of an aglycone
      and a primary alcoholic function at C-24 and differing functions at C-30. Among
      these, compounds 1-3 and 6 showed a secondary alcoholic function at C-11, which
      is methoxylated in compounds 4 and 7. Compound 5 was shown to possess a known
      aglycone, wistariasapogenol A; however, it is described here for the first time
      as a saponin constituent of the Trifolium genus. Some aspects of taxonomic
      classification of zigzag clover are also discussed. 

PMID- 24098958
TI  - Joint associations of body mass index and waist-to-height ratio with sleep
      duration among Saudi adolescents.
AB  - BACKGROUND: Numerous studies have shown significant associations between short
      sleep duration and overall or abdominal obesity. However, no study has reported
      on the joint association of body mass index (BMI) and waist-to-height ratio
      (WHtR) with sleep duration in adolescents. AIM: To examine the joint associations
      of BMI and WHtR with sleep duration among Saudi adolescents. SUBJECTS AND
      METHODS: A school-based cross-sectional study was conducted involving 2852
      secondary-school students (51.7% females) aged 15-19 years, randomly selected
      using a multistage stratified cluster sampling. Self-reported sleep duration was
      assessed and BMI was classified into high and low categories according to the
      IOTF classification, whereas WHtR categories were based on above and below 0.5.
      RESULTS: The low BMI-low WHtR category had the longest mean sleep duration (7.27
      hours/day), whereas the high BMI-high WHtR group had the shortest sleep duration
      (7.02 hours/day; p = 0.003) (aOR = 0.832, 95% CI = 0.698-0.992, p = 0.040). In
      addition, high BMI-low WHtR or low BMI-high WHtR groups didn't significantly
      associate with reduced sleep duration among adolescents. CONCLUSION: The joint
      association of high BMI-high WHtR increases adolescent's risk of having reduced
      sleep duration. Future research should seek to confirm such findings and provide
      an explanation for this association.

PMID- 24098959
TI  - Cell-cycle regulated transcription associates with DNA replication timing in
      yeast and human.
AB  - BACKGROUND: Eukaryotic DNA replication follows a specific temporal program, with
      some genomic regions consistently replicating earlier than others, yet what
      determines this program is largely unknown. Highly transcribed regions have been
      observed to replicate in early S-phase in all plant and animal species studied to
      date, but this relationship is thought to be absent from both budding yeast and
      fission yeast. No association between cell-cycle regulated transcription and
      replication timing has been reported for any species. RESULTS: Here I show that
      in budding yeast, fission yeast, and human, the genes most highly transcribed
      during S-phase replicate early, whereas those repressed in S-phase replicate
      late. Transcription during other cell-cycle phases shows either the opposite
      correlation with replication timing, or no relation. The relationship is
      strongest near late-firing origins of replication, which is not consistent with a
      previously proposed model-that replication timing may affect transcription-and
      instead suggests a potential mechanism involving the recruitment of limiting
      replication initiation factors during S-phase. CONCLUSIONS: These results suggest
      that S-phase transcription may be an important determinant of DNA replication
      timing across eukaryotes, which may explain the well-established association
      between transcription and replication timing.

PMID- 24098960
TI  - Relations of parenting quality, interparental conflict, and overnights with
      mental health problems of children in divorcing families with high legal
      conflict.
AB  - The current study examined the associations between child mental health problems
      and the quality of maternal and paternal parenting, and how these associations
      were moderated by three contextual factors: quality of parenting by the other
      parent, interparental conflict, and the number of overnights parents had with the
      child. Data for the current study came from a sample of divorcing families who
      are in high legal conflict over developing or maintaining a parenting plan
      following divorce. Analyses revealed that the associations between child mental
      health problems and positive maternal and paternal parenting were moderated by
      the quality of parenting provided by the other parent and by the number of
      overnights children spent with parents, but not by the level of interparental
      conflict. When parenting by the other parent and number of overnights were
      considered together in the same model, only number of overnights moderated the
      relations between parenting and child-behavior problems. The results support the
      proposition that the well-being of children in high-conflict divorcing families
      is better when they spend adequate time with at least one parent who provides
      high-quality parenting.

PMID- 24098961
TI  - Asymmetric partner pronoun use and demand-withdraw interaction in couples coping
      with health problems.
AB  - Recent research links first-person plural pronoun use (we-talk) by individual
      romantic partners to adaptive relationship functioning and individual health
      outcomes. To examine a possible boundary condition of adaptive we-talk in couples
      coping with health problems, we correlated asymmetric couple-level we/I-ratios
      (more we-talk relative to I-talk by the spouse than the patient) with a
      concurrent pattern of directional demand-withdraw (D-W) interaction in which the
      spouse demands change while the patient withdraws. Couples in which a partner who
      abused alcohol (n = 65), smoked cigarettes despite having heart or lung disease
      (n = 24), or had congestive heart failure (n = 58) discussed a health-related
      disagreement during a video-recorded interaction task. Transcripts of these
      conversations provided measures of pronoun use for each partner, and trained
      observers coded D-W patterns from the recordings. As expected, partner asymmetry
      in we/I-ratio scores predicted directional demand-withdraw, such that spouses who
      used more we-talk (relative to I-talk) than patients tended to assume the demand
      role in concurrent D-W interaction. Asymmetric I-talk rather than we-talk
      accounted for this association, and asymmetric you-talk contributed independently
      as well. In contrast to previous studies of we-talk by individual partners, the
      present results identify dyad-level pronoun patterns that clearly do not mark
      beneficent processes: asymmetric partner we/I-ratios and you-talk reflect
      problematic demand-withdraw interaction.

PMID- 24098962
TI  - Patterns of intimate partner violence in a large, epidemiological sample of
      divorcing couples.
AB  - In many jurisdictions divorcing couples are court-ordered to participate in
      divorce mediation to resolve parenting plan disputes prior to a court allowing a
      case to proceed to trial. Historically, a significant number (40-80%) of these
      divorcing couples enter this highly stressful legal process having experienced
      violence and abuse within the relationship (Pearson, 1997). Several researchers
      have developed typologies that describe couple-level patterns of Intimate Partner
      Violence and Abuse (IPV/A) behaviors; one research team suggested their typology
      could apply specifically to such divorcing people (Kelly & Johnson, 2008). In
      this context, identification and accurate classification of IPV/A can lead to
      better decisions as long-term, difficult to modify custody orders concerning the
      children are made during divorce mediation. Accurate identification and
      classification of IPV/A can also assist clinical researchers designing
      specialized interventions for couples and individuals experiencing IPV/A, mental
      health practitioners who may treat these families, and custody evaluators who may
      make recommendations to the courts. The current study includes a large
      epidemiological sample of divorcing couples and provides a robust statistical
      solution with five distinct categories of IPV/A. Two of the five categories were
      similar to those proposed by Johnson (2006c). The current study also provides
      descriptions and frequencies of each type of IPV/A, and discusses implications
      for court personnel, researchers and practitioners.

PMID- 24098963
TI  - Family income and appraisals of parental conflict as predictors of psychological
      adjustment and diurnal cortisol in emerging adulthood.
AB  - The goal of the current study was to provide the first investigation of whether
      appraisals of parental marital conflict mediate associations of family income
      with emerging adult psychological adjustment and diurnal cortisol production.
      Participants were 178 college students who provided 3 saliva samples across the
      day and reported their family income, adjustment (depressive symptoms, perceived
      daily stress, internalizing problems, and externalizing problems), and appraisals
      of their parents' conflict (including perceptions of frequency, intensity,
      resolution, stability, as well as perceived threat and self-blame for conflict).
      Results indicated that emerging adults from low-income families reported more
      negative conflict appraisals, which in turn predicted lower levels of adjustment;
      there was no association between income and patterns of cortisol production
      across the day. However, emerging adults who felt responsible for their parents'
      conflict displayed cortisol levels that were lower early in the day, with a
      tendency toward blunted cortisol slopes across the day; those who appraised their
      parents' conflict less negatively displayed a more normative pattern of cortisol
      production. These results suggest that effects of family income on psychological
      adjustment are explained, in part, by appraisals of parental conflict,
      particularly of appraisals of conflict as threatening, whereas self-blame
      conflict appraisals have main effects on cortisol, and predict a dysregulated and
      potentially maladaptive pattern of cortisol production across the day for
      emerging adults.

PMID- 24098964
TI  - Does dyadic coping mediate the relationship between emotional intelligence (EI)
      and marital quality?
AB  - This study tested for the mediational effects of dyadic coping in the observed
      relationship between emotional intelligence, assessed both as ability and as
      trait, and quality of marital relations. We used a standard dyadic design
      involving 100 newlywed heterosexual couples who were assessed on EI measures
      along with measures of dyadic coping and perceived marital quality. Total dyadic
      coping, as well as dyadic coping of oneself and dyadic coping of partner, were
      observed to mediate the association between EI and marital quality. These data
      provide some support for the commonly held assumption that EI plays a role in
      marital relationships, as mediated by dyadic coping. However, whereas the
      individual appears to benefit from being emotionally intelligent, the benefit is
      not transmitted to the other partner in the relationship.

PMID- 24098965
TI  - Stable superhydrophobic surface of hierarchical carbon nanotubes on Si
      micropillar arrays.
AB  - It is of great importance to construct a stable superhydrophobic surface with low
      sliding angle (SA) for various applications. We used hydrophobic carbon nanotubes
      (CNTs) to construct the superhydrophobic hierarchical architecture of CNTs on
      silicon micropillar array (CNTs/Si-MUp), which have a large contact angle of 153
      degrees  to 155 degrees  and an ultralow SA of 3 degrees  to 5 degrees . Small
      water droplets with a volume larger than 0.3 MUL can slide on the CNTs/Si-MUp
      with a tilted angle of approximately 5 degrees . The CNTs growing on planar Si
      wafer lose their superhydrophobic properties after exposing to tiny water
      droplets. However, the CNTs/Si-MUp still show superhydrophobic properties even
      after wetting using tiny water droplets. The CNTs/Si-MUp still have a
      hierarchical structure after wetting, resulting in a stable superhydrophobic
      surface. 

PMID- 24098966
TI  - Pd(II)-catalyzed ortho-trifluoromethylation of benzylamines.
AB  - The Pd(II)-catalyzed ortho-C-H trifluoromethylation of benzylamines has been
      achieved utilizing an electrophilic CF3 reagent. Additives, such as H2O and Ag2O,
      were found to be crucial for obtaining good yields. This protocol will be useful
      in medicinal chemistry for the preparation of ortho-trifluoromethyl-substituted
      benzylamines. 

PMID- 24098967
TI  - Quality of life and other outcome measures in caregivers of patients with
      schizophrenia.
AB  - There is a growing concern about caregivers of individuals with schizophrenia who
      assume almost the totality of the patient care. This responsibility exposes them
      to an intense burden with negative consequences for them and indirectly for
      patients' health. The aim of this study was to provide an overview of the content
      and psychometric properties of instruments assessing the experience of caregivers
      of individuals with schizophrenia. Of the 460 articles screened from 1990 to
      2013, 16 instruments were identified focusing on caregivers' burden (8), coping
      strategies (3), perception of need (3) and quality of life (2). These instruments
      were based primarily on experts' opinions, except two which were based
      exclusively on caregivers' view. The psychometric properties were poorly
      documented for a number of them and no information was published about
      responsiveness. Future works are needed to involve caregivers in the development
      of instruments and to explore psychometric properties of these instruments. 

PMID- 24098968
TI  - Chemical composition and antioxidant capacities of phytococktail extracts from
      trans-Himalayan cold desert.
AB  - BACKGROUND: Himalayan plants are widely used in traditional system of medicine
      both as prophylactics and therapeutics for high altitude maladies. Our aim was to
      evaluate the antioxidant capacities and bioactive compounds of methanol and n
      hexane extracts of the phytococktail comprising of sea buckthorn (Hippophae
      rhamnoides), apricot (Prunus armeniaca) and roseroot (Rhodiola imbricata) from
      trans-Himalaya. METHODS: The 1,1-diphenyl-2-picrylhydrazyl (DPPH), 2,2'-azinobis
      (3-ethylbenzothiazoline-6-sulfonic acid) diammonium salt (ABTS) and nitric oxide
      (NO) radical scavenging capacities and lipid peroxidation inhibition (LPI)
      property of the extracts were determined. Total antioxidant power was determined
      by ferric reducing/antioxidant power (FRAP) assay. Total polyphenol, flavonoid,
      flavonol, proanthocyanidin and carotenoid were also estimated for both extracts.
      We have identified and quantified the phyto-chemotypes present in the methanol
      and n-hexane extracts by hyphenated gas chromatography/mass spectrometry (GC/MS)
      technique. RESULTS: Antioxidant capacity assays using DPPH, ABTS, NO, LPI and
      FRAP exhibited analogous results where the phytococktail showed high antioxidant
      action. The phytococktail was also found to possess high quantity of total
      polyphenol, flavonoid, flavonol and carotenoid. A significant and linear
      correlation was found between the antioxidant capacities and bioactive
      principles. A total of 32 phyto-chemotypes were identified from these extracts by
      GC/MS chemometric fingerprinting. Major phyto-chemotypes identified by GC/MS were
      glycosides, phenylpropanoids and derivatives, terpenoids, alkaloids,
      phytosterols, fatty acids and esters, alkaloids and derivatives, organic acid
      esters and aromatic ethers with positive biological and pharmacological actions.
      CONCLUSION: The phytococktail extracts were found to contain considerable amount
      of diverse bioactive compounds with high antioxidant capacities. The presence of
      hydrophilic and lipophilic antioxidants in the phytococktail could have
      contributed to the higher antioxidant values. Hence, the phytococktail could be
      used as natural source of antioxidants to ameliorate disorders associated with
      oxidative stress.

PMID- 24098969
TI  - Experimental and theoretical studies on the movements of two bubbles in an
      acoustic standing wave field.
AB  - When subjected to an ultrasonic standing-wave field, cavitation bubbles smaller
      than the resonance size migrate to the pressure antinodes. As bubbles approach
      the antinode, they also move toward each other and either form a cluster or
      coalesce. In this study, the translational trajectory of two bubbles moving
      toward each other in an ultrasonic standing wave at 22.4 kHz was observed using
      an imaging system with a high-speed video camera. This allowed the speed of the
      approaching bubbles to be measured for much closer distances than those reported
      in the prior literature. The trajectory of two approaching bubbles was modeled
      using coupled equations of radial and translational motions, showing similar
      trends with the experimental results. We also indirectly measured the secondary
      Bjerknes force by monitoring the acceleration when bubbles are close to each
      other under different acoustic pressure amplitudes. Bubbles begin to accelerate
      toward each other as the distance between them gets shorter, and this
      acceleration increases with increasing acoustic pressure. The current study
      provides experimental data that validates the theory on the movement of bubbles
      and forces acting between them in an acoustic field that will be useful in
      understanding bubble coalescence in an acoustic field. 

PMID- 24098973
TI  - Palladium-catalyzed regioselective C-5 arylation of protected L-histidine:
      microwave-assisted C-H activation adjacent to donor arm.
AB  - An efficient, microwave-assisted direct C-H arylation at the C-5 position of
      fully protected L-histidine has been achieved via a palladium-catalyzed
      transformation reaction. This highly regioselective reaction has been applied to
      synthesize a series of protected 5-aryl-L-histidines using aryl iodides as
      coupling partners, in good to excellent yields. The reaction is compatible with
      substrates possessing electron-donating or electron-withdrawing substituents and
      offers high reactive functional group tolerance.

PMID- 24098972
TI  - Facile engineering of xeno-free microcarriers for the scalable cultivation of
      human pluripotent stem cells in stirred suspension.
AB  - A prerequisite for the realization of human pluripotent stem cell (hPSC)
      therapies is the development of bioprocesses for generating clinically relevant
      quantities of undifferentiated hPSCs and their derivatives under xeno-free
      conditions. Microcarrier stirred-suspension bioreactors are an appealing modality
      for the scalable expansion and directed differentiation of hPSCs. Comparative
      analyses of commercially available microcarriers clearly show the need for
      developing synthetic substrates supporting the adhesion and growth of hPSCs in
      three-dimensional cultures under agitation-induced shear. Moreover, the low
      seeding efficiencies during microcarrier loading with hPSC clusters poses a
      significant process bottleneck. To that end, a novel protocol was developed
      increasing hPSC seeding efficiency from 30% to over 80% and substantially
      shortening the duration of microcarrier loading. Importantly, this method was
      combined with the engineering of polystyrene microcarriers by surface conjugation
      of a vitronectin-derived peptide, which was previously shown to support the
      growth of human embryonic stem cells. Cells proliferated on peptide-conjugated
      beads in static culture but widespread detachment was observed after exposure to
      stirring. This prompted additional treatment of the microcarriers with a
      synthetic polymer commonly used to enhance cell adhesion. hPSCs were successfully
      cultivated on these microcarriers in stirred suspension vessels for multiple
      consecutive passages with attachment efficiencies close to 40%. Cultured cells
      exhibited on average a 24-fold increase in concentration per 6-day passage, over
      85% viability, and maintained a normal karyotype and the expression of
      pluripotency markers such as Nanog, Oct4, and SSEA4. When subjected to
      spontaneous differentiation in embryoid body cultures or directed differentiation
      to the three embryonic germ layers, the cells adopted respective fates displaying
      relevant markers. Lastly, engineered microcarriers were successfully utilized for
      the expansion and differentiation of hPSCs to mesoderm progeny in stirred
      suspension vessels. Hence, we demonstrate a strategy for the facile engineering
      of xeno-free microcarriers for stirred-suspension cultivation of hPSCs. Our
      findings support the use of microcarrier bioreactors for the scalable, xeno-free
      propagation and differentiation of human stem cells intended for therapies. 

PMID- 24098975
TI  - Differences in the mutation of the p53 gene in exons 6 and 7 in cervical samples
      from HIV- and HPV-infected women.
AB  - BACKGROUND: Human Papillomavirus (HPV) infection is a serious problem for human
      immunodeficiency virus (HIV)-infected women, increases their risk of cervical
      lesions and cancer. In cervical carcinogenesis, mutations in the p53 gene occur
      most frequently within exons 5-8. To our knowledge, no previous studies have
      analyzed mutations in exons 5-8 of the p53 gene in HIV- and HPV-infected women.
      In our study, we verified these mutations in women with and without cervical
      abnormalities. FINDINGS: The study included 160 women, divided into three groups:
      (1) 83 HPV- and HIV-infected women (HIV group); (2) 37 HPV-infected/HIV
      uninfected (control group); and (3) 40 normal cytology/DNA-HPV negative/HIV
      uninfected women (negative control p53 reactions). HPV-DNA was detected using
      polymerase chain reaction (PCR) and genotyping by PCR-restriction fragment length
      polymorphism analysis. Using primers for exons 5-8, the mutation of the p53 gene
      was verified by PCR-single strand conformational polymorphism. The total mutation
      of the p53 gene in exons 5-8 was not significantly associated with the HIV and
      control groups. The mutations in exon 7 were the highest in the HIV group (43.8%)
      and in exon 6 in the control group (57.2%) (p = 0.0793) suggesting a tendency
      toward differential mutation in exon 7 in the HIV group. CONCLUSIONS: Our study
      provides preliminary evidence that the mutation in exon 7 might be an important
      differentiating factor for cervical carcinogenesis in HIV-infected women. This
      aspect deserves an additional cross-sectional and longitudinal study using a
      larger sample size with a higher number of High-grade squamous intraephitelial
      lesion (HSIL) to observe the evolution of cervical lesions.

PMID- 24098974
TI  - Comprehensive analysis of RNA-seq data reveals the complexity of the
      transcriptome in Brassica rapa.
AB  - BACKGROUND: The species Brassica rapa (2n=20, AA) is an important vegetable and
      oilseed crop, and serves as an excellent model for genomic and evolutionary
      research in Brassica species. With the availability of whole genome sequence of
      B. rapa, it is essential to further determine the activity of all functional
      elements of the B. rapa genome and explore the transcriptome on a genome-wide
      scale. Here, RNA-seq data was employed to provide a genome-wide transcriptional
      landscape and characterization of the annotated and novel transcripts and
      alternative splicing events across tissues. RESULTS: RNA-seq reads were generated
      using the Illumina platform from six different tissues (root, stem, leaf, flower,
      silique and callus) of the B. rapa accession Chiifu-401-42, the same line used
      for whole genome sequencing. First, these data detected the widespread
      transcription of the B. rapa genome, leading to the identification of numerous
      novel transcripts and definition of 5'/3' UTRs of known genes. Second, 78.8% of
      the total annotated genes were detected as expressed and 45.8% were
      constitutively expressed across all tissues. We further defined several groups of
      genes: housekeeping genes, tissue-specific expressed genes and co-expressed genes
      across tissues, which will serve as a valuable repository for future crop
      functional genomics research. Third, alternative splicing (AS) is estimated to
      occur in more than 29.4% of intron-containing B. rapa genes, and 65% of them were
      commonly detected in more than two tissues. Interestingly, genes with high rate
      of AS were over-represented in GO categories relating to transcriptional
      regulation and signal transduction, suggesting potential importance of AS for
      playing regulatory role in these genes. Further, we observed that intron
      retention (IR) is predominant in the AS events and seems to preferentially
      occurred in genes with short introns. CONCLUSIONS: The high-resolution RNA-seq
      analysis provides a global transcriptional landscape as a complement to the B.
      rapa genome sequence, which will advance our understanding of the dynamics and
      complexity of the B. rapa transcriptome. The atlas of gene expression in
      different tissues will be useful for accelerating research on functional genomics
      and genome evolution in Brassica species.

PMID- 24098976
TI  - Influence of CCR5 and CCR2 genetic variants in the resistance/susceptibility to
      HIV in serodiscordant couples from Colombia.
AB  - The main genetic factor related to HIV-1 resistance is the CCR5-Delta32 mutation;
      however, the homozygous genotype is uncommon. The CCR5-Delta32 mutation along
      with single nucleotide polymorphisms (SNPs) in the CCR5 promoter and the CCR2
      V64I mutation have been included in seven human haplogroups (HH) previously
      associated with resistance/susceptibility to HIV-1 infection and different rates
      of AIDS progression. Here, we determined the association of the CCR5 promoter
      SNPs, the CCR5-Delta32 mutation, CCR2-V64I SNP, and HH frequencies with
      resistance/susceptibility to HIV-1 infection in a cohort of HIV-1-serodiscordant
      couples from Colombia. Seventy HIV-1-exposed, but seronegative (HESN)
      individuals, 57 seropositives (SP), and 112 healthy controls (HC) were included.
      The CCR5-Delta32 mutation and CCR2-V64I SNP were identified by PCR, and the CCR5
      promoter SNPs were evaluated by sequencing. None of the individuals exhibited a
      homozygous Delta32 genotype; the CCR2-I allele was more frequent in HESN (34%)
      than HC (23%) (p=0.039, OR=1.672). The frequency of the 29G allele was higher in
      SP than HC (p=0.003, OR=3). HHF2 showed a higher frequency in HC (19%) than SP
      (9%) (p=0.027), while HHG1 was more frequent in SP (11.1%) than in HC (4.2%)
      (p=0.019). The AGACCAC-CCR2-I-CCR5 wild-type haplotype showed a higher frequency
      in SP (14.2%) than in HC (3.7%) (p=0.001). In conclusion, the CCR5-Delta32 allele
      is not responsible for HIV-1 resistance in this HESN group; however, the CCR2-I
      allele could be protective, while the 29G allele might increase the likelihood of
      acquiring HIV-1 infection. HHG1 and the AGACCAC-CCR2-I-CCR5 wild-type haplotype
      might promote HIV-1 infection while HHF2 might be related to resistance. However,
      additional studies are required to evaluate the implications of these findings.

PMID- 24098977
TI  - Trends in birth weight and the prevalence of low birth weight and small-for
      gestational-age in Surinamese South Asian babies since 1974: cross-sectional
      study of three birth cohorts.
AB  - BACKGROUND: South Asian babies born in developed countries are generally lighter
      than babies from other ethnic groups born in the same country. While the mean
      birth weight of Caucasian babies in the Netherlands has increased the past
      decades, it is unknown if the mean birth weight of South Asian babies born in the
      Netherlands has increased or if the prevalence of low birth weight (LBW) or small
      for-gestational-age (SGA) has decreased.The aims of this study are: 1. to
      investigate secular changes in mean birth weight and the prevalence of LBW and
      SGA in Surinamese South Asian babies, and 2. to assess differences between
      Surinamese South Asian and Dutch Caucasian neonates born 2006-2009. METHODS: A
      population based study for which neonatal characteristics of 2014 Surinamese
      South Asian babies, born between 1974 and 2009 in the Netherlands, and 3104 Dutch
      Caucasian babies born 2006-2009 were obtained from well-baby clinic records. LBW
      was defined as a birth weight <2500 g. SGA was based on a universal population
      standard (the Netherlands) and three ethnic specific standards (the Netherlands,
      UK, Canada). RESULTS: In Surinamese South Asian babies from 1974 to 2009 no
      secular trend in mean birth weight and prevalence of LBW was found, whereas SGA
      prevalence decreased significantly.Surinamese South Asian babies born in 2006
      2009 (2993 g; 95% CI 2959-3029 g) were 450 g lighter than Dutch Caucasian babies
      (3448 g; 95% CI 3429-3468 g), while LBW and SGA prevalences, based on universal
      standards, were three times higher. Application of ethnic specific standards from
      the Netherlands and the UK yielded SGA rates in Surinamese South Asian babies
      that were similar to Dutch. There were considerable differences between the
      standards used. CONCLUSION: Since 1974, although the mean birth weight of
      Surinamese South Asian babies remained unchanged, they gained a healthier weight
      for their gestational age.

PMID- 24098978
TI  - Meat quality and nutritional composition of pheasants (Phasianus colchicus)
      reared in an extensive system.
AB  - 1. Carcass cuts, chemical composition, colour, textural parameters, fatty acid
      and amino acid profiles, macro- and micromineral content and sensory properties
      of breast and drumstick meat from 10 month old common pheasant produced in an
      extensive rearing system were analysed. 2. Breast muscle was characterised by a
      high concentration of protein (254 g/kg), low content of intramuscular fat (1.3
      g/kg), considerable amount of Fe-haeme (4.9 mg/kg) low shear force (1.96
      kg/cm(2)) and hardness (4.07 kg/cm(2)). 3. The main drumstick characteristics
      were 222 g of protein/kg, 4.0 g of intramuscular fat/g and a significant higher
      cholesterol concentration compared to that of breast (7.7 vs. 2.9 g/kg). 4.
      Saturated, monounsaturated and polyunsaturated fatty acid mean values for both
      muscle types were approximately 34.5%, 43.3% and 24.2% of total fatty acid methyl
      esters, respectively, and n-3 content in breast was significantly higher (3.21%
      vs. 1.65%). Significant differences were found between the three tissues (breast,
      drumstick and subcutaneous fat). 5. Large differences in the amino acid profile
      between breast and drumstick were detected, especially in the non-essential
      fraction. The main essential amino acids were lysine and leucine, whereas
      aspartic and glutamic acids were the most important non-essential amino acids. 6.
      There were significant differences between muscle types in the mineral content
      with regard to iron, magnesium, sodium and zinc. Pheasant meat is a good
      nutritional source of iron as 100 g of drumstick may provide 23.6% of the
      recommended daily amount.

PMID- 24098979
TI  - On-line mass spectrometric methods for the determination of the primary products
      of fast pyrolysis of carbohydrates and for their gas-phase manipulation.
AB  - Mass spectrometric methodology was developed for the determination and
      manipulation of the primary products of fast pyrolysis of carbohydrates. To
      determine the true primary pyrolysis products, a very fast heating pyroprobe was
      coupled to a linear quadrupole ion trap mass spectrometer through a custom-built
      adaptor. A home-built flow tube that simulates pyrolysis reactor conditions was
      used to examine the secondary reactions of the primary products. Depending on the
      experiment, the pyrolysis products were either evaporated and quenched or allowed
      to react for a period of time. The quenched products were ionized in an
      atmospheric pressure chemical ionization (APCI) source infused with one of two
      ionization reagents, chloroform or ammonium hydroxide, to aid in ionization.
      During APCI in negative ion mode, chloroform produces chloride anions that are
      known to readily add to carbohydrates with little bias and little to no
      fragmentation. On the other hand, in positive ion mode APCI, ammonium hydroxide
      forms ammonium adducts with carbohydrates with little to no fragmentation. The
      latter method ionizes compounds that are not readily ionized upon negative ion
      mode APCI, such as furan derivatives. Six model compounds were studied to verify
      the ability of the ionization methods to ionize known pyrolysis products:
      glycolaldehyde, hydroxyacetone, furfural, 5-hydroxymethylfurfural, levoglucosan,
      and cellobiosan. The method was then used to examine fast pyrolysis of
      cellobiose. The primary fast pyrolysis products were determined to consist of
      only a handful of compounds that quickly polymerize to form anhydro
      oligosaccharides when allowed to react at high temperatures for an extended
      period of time. 

PMID- 24098980
TI  - Anti-cancer activity of anti-GLUT1 antibody-targeted polymeric micelles co-loaded
      with curcumin and doxorubicin.
AB  - BACKGROUND: Treatment of late stage cancers has proven to be a very difficult
      task. Targeted therapy and combinatory drug administration may be the solution.
      PURPOSE: The study was performed to evaluate the therapeutic efficacy of PEG-PE
      micelles, co-loaded with curcumin (CUR) and doxorubicin (DOX), and targeted with
      anti-GLUT1 antibody (GLUT1) against HCT-116 human colorectal adenocarcinoma cells
      both in vitro and in vivo. METHODS: HCT-116 cells were treated with non-targeted
      and GLUT1-targeted CUR and DOX micelles as a single agent or in combination.
      Cells were inoculated in female nude mice. Established tumors were treated with
      the micellar formulations at a dose of 4 mg/kg CUR and 0.4 mg/kg DOX every 2 d
      for a total of 7 injections. RESULTS: CUR + DOX-loaded micelles decorated with
      GLUT1 had a robust killing effect even at low doses of DOX in vitro. At the doses
      chosen, non-targeted CUR and CUR + DOX micelles did not exhibit any significant
      tumor inhibition versus control. However, GLUT1-CUR and GLUT1-CUR + DOX micelles
      showed a significant tumor inhibition effect with an improvement in survival.
      CONCLUSION: We showed a dramatic improvement in efficacy between the non-targeted
      and GLUT1-targeted formulations both in vitro and in vivo. Hence, we confirmed
      that GLUT1-CUR + DOX micelles are effective and deserve further investigation.

PMID- 24098982
TI  - Fragment-to-hit-to-lead discovery of a novel pyridylurea scaffold of ATP
      competitive dual targeting type II topoisomerase inhibiting antibacterial agents.
AB  - The discovery and optimization of a new class of bacterial topoisomerase (DNA
      gyrase and topoisomerase IV) inhibitors binding in the ATP domain are described.
      A fragment molecule, 1-ethyl-3-(2-pyridyl)urea, provided sufficiently potent
      enzyme inhibition (32 MUM) to prompt further analogue work. Acids and acid
      isosteres were incorporated at the 5-pyridyl position of this fragment, bridging
      to a key asparagine residue, improving enzyme inhibition, and leading to
      measurable antibacterial activity. A CF3-thiazole substituent at the 4-pyridyl
      position improved inhibitory potency due to a favorable lipophilic interaction.
      Promising antibacterial activity was seen versus the Gram-positive pathogens
      Staphylococcus aureus and Streptococcus pneumoniae and the Gram-negative
      pathogens Haemophilus influenzae and Moraxella catarrhalis . Precursor metabolite
      incorporation and mutant analysis studies support the mode-of-action, blockage of
      DNA synthesis by dual target topoisomerase inhibition. Compound 35 was
      efficacious in a mouse S. aureus disease model, where a 4.5-log reduction in
      colony forming units versus control was demonstrated. 

PMID- 24098983
TI  - Marked reduction in mortality in patients with severe traumatic brain injury.
AB  - OBJECT: In spite of evidence that use of the Brain Trauma Foundation Guidelines
      for the Management of Severe Traumatic Brain Injury (Guidelines) would
      dramatically reduce morbidity and mortality, adherence to these Guidelines
      remains variable across trauma centers. The authors analyzed 2-week mortality due
      to severe traumatic brain injury (TBI) from 2001 through 2009 in New York State
      and examined the trends in adherence to the Guidelines. METHODS: The authors
      calculated trends in adherence to the Guidelines and age-adjusted 2-week
      mortality rates between January 1, 2001, and December 31, 2009. Univariate and
      multivariate logistic regression analyses were performed to evaluate the effect
      of time period on case-fatality. Intracranial pressure (ICP) monitor insertion
      was modeled in a 2-level hierarchical model using generalized linear mixed
      effects to allow for clustering by different centers. RESULTS: From 2001 to 2009,
      the case-fatality rate decreased from 22% to 13% (p < 0.0001), a change that
      remained significant after adjusting for factors that independently predict
      mortality (adjusted OR 0.52, 95% CI 0.39-0.70; p < 0.0001). Guidelines adherence
      increased, with the percentage of patients with ICP monitoring increasing from
      56% to 75% (p < 0.0001). Adherence to cerebral perfusion pressure treatment
      thresholds increased from 15% to 48% (p < 0.0001). The proportion of patients
      having an ICP elevation greater than 25 mm Hg dropped from 42% to 29% (p =
      0.0001). CONCLUSIONS: There was a significant reduction in TBI mortality between
      2001 and 2009 in New York State. Increase in Guidelines adherence occurred at the
      same time as the pronounced decrease in 2-week mortality and decreased rate of
      intracranial hypertension, suggesting a causal relationship between Guidelines
      adherence and improved outcomes. Our findings warrant future investigation to
      identify methods for increasing and sustaining adherence to evidence-based
      Guidelines recommendations.

PMID- 24098981
TI  - Evolution of bilaterian central nervous systems: a single origin?
AB  - The question of whether the ancestral bilaterian had a central nervous system
      (CNS) or a diffuse ectodermal nervous system has been hotly debated. Considerable
      evidence supports the theory that a CNS evolved just once. However, an
      alternative view proposes that the chordate CNS evolved from the ectodermal nerve
      net of a hemichordate-like ancestral deuterostome, implying independent evolution
      of the CNS in chordates and protostomes. To specify morphological divisions along
      the anterior/posterior axis, this ancestor used gene networks homologous to those
      patterning three organizing centers in the vertebrate brain: the anterior neural
      ridge, the zona limitans intrathalamica and the isthmic organizer, and subsequent
      evolution of the vertebrate brain involved elaboration of these ancestral
      signaling centers; however, all or part of these signaling centers were lost from
      the CNS of invertebrate chordates. The present review analyzes the evidence for
      and against these theories. The bulk of the evidence indicates that a CNS evolved
      just once - in the ancestral bilaterian. Importantly, in both protostomes and
      deuterostomes, the CNS represents a portion of a generally neurogenic ectoderm
      that is internalized and receives and integrates inputs from sensory cells in the
      remainder of the ectoderm. The expression patterns of genes involved in
      medio/lateral (dorso/ventral) patterning of the CNS are similar in protostomes
      and chordates; however, these genes are not similarly expressed in the ectoderm
      outside the CNS. Thus, their expression is a better criterion for CNS homologs
      than the expression of anterior/posterior patterning genes, many of which (for
      example, Hox genes) are similarly expressed both in the CNS and in the remainder
      of the ectoderm in many bilaterians. The evidence leaves hemichordates in an
      ambiguous position - either CNS centralization was lost to some extent at the
      base of the hemichordates, or even earlier, at the base of the hemichordates +
      echinoderms, or one of the two hemichordate nerve cords is homologous to the CNS
      of protostomes and chordates. In any event, the presence of part of the genetic
      machinery for the anterior neural ridge, the zona limitans intrathalamica and the
      isthmic organizer in invertebrate chordates together with similar morphology
      indicates that these organizers were present, at least in part, at the base of
      the chordates and were probably elaborated upon in the vertebrate lineage. 

PMID- 24098985
TI  - On scholarly writing.

PMID- 24098986
TI  - More on gap analysis.
AB  - Continuing education providers continue to struggle with the concept of gap
      analysis, a required component of the needs assessment process in the American
      Nurses Credentialing Center accreditation program. This column offers information
      on identifying a gap and examples of how this fits into the planning process.

PMID- 24098984
TI  - Effects of exercise and diet change on cognition function and synaptic plasticity
      in high fat diet induced obese rats.
AB  - BACKGROUND: Nutritional imbalance-induced obesity causes a variety of diseases
      and in particular is an important cause of cognitive function decline. This study
      was performed on Sprague Dawley (SD) rats with 13-weeks of high fat diet-induced
      obesity in connection to the effects of regular exercise and dietary control for
      8 weeks on the synaptic plasticity and cognitive abilities of brain. METHODS:
      Four weeks-old SD rats were adopted classified into normal-normal diet-sedentary
      (NNS, n = 8), obesity-high fat diet-sedentary (OHS, n = 8), obesity-high fat diet
      training (OHT, n = 8), obesity-normal diet-sedentary (ONS, n = 8) and obesity-
      normal diet-training (ONT, n = 8). The exercise program consisted of a treadmill
      exercise administered at a speed of 8 m/min for 1-4 weeks, and 14 m/min for 5-8
      weeks. The Western blot method was used to measure the expression of NGF, BDNF,
      p38MAPK and p-p38MAPK proteins in hippocampus of the brain, and expressions of
      NGF, BDNF, TrkA, TrkB, CREB and synapsin1 mRNA were analyzed through qRT-PCR.
      RESULTS: The results suggest cognitive function-related protein levels and mRNA
      expression to be significantly decreased in the hippocampus of obese rats, and
      synaptic plasticity as well as cognitive function signaling sub-pathway factors
      were also significantly decreased. In addition, 8-weeks exercises and treatment
      by dietary change had induced significant increase of cognitive function-related
      protein levels and mRNA expression as well as synaptic plasticity and cognitive
      function signaling sub-pathway factors in obese rats. In particular, the combined
      treatment had presented even more positive effect. CONCLUSIONS: Therefore, it was
      determined that the high fat diet-induced obesity decreases plasticity and
      cognitive function of the brain, but was identified as being improved by
      exercises and dietary changes. In particular, it is considered that regular
      exercise has positive effects on memory span and learning capacity unlike dietary
      control.

PMID- 24098987
TI  - Using social media to share the death experience: discussion points.
AB  - Poignant tweets by a well-known journalist led to a national conversation about
      publicly sharing the death experience. The purpose of this column is to set the
      stage for a broader discussion among health care providers to understand the
      perceived benefits and related challenges of using social media to share the
      death experience.

PMID- 24098988
TI  - The flipped classroom for professional development: part I. Benefits and
      strategies.
AB  - Individualizing the educational encounter is supported by flipping the classroom
      experience. This column offers an overview and describes the benefits of flipping
      the classroom. Part II will explore the practicalities and pedagogy of lecture
      capture using podcasts and videos, a technology strategy used in flipping the
      classroom.

PMID- 24098990
TI  - Recombinant cancer vaccines and new vaccine targets. Interview by Jenaid Rees.
AB  - Interview by Jenaid Rees, Commissioning Editor Jeffrey Schlom obtained his PhD
      from Rutgers University (NJ, USA). After obtaining his PhD, he worked at Columbia
      University (NY, USA) before moving in 1973 to the National Cancer Institute,
      National Institutes of Health (MD, USA). Since then he has served as the Chief of
      several sections, including his present position as the Chief of the Laboratory
      of Tumor Immunology and Biology in the Center for Cancer Research which he has
      held for the past 30 years. During this period, he has worked as an Adjunct
      Professor at George Washington University (Washington, DC, USA), served on the
      Editorial Board of several journals and holds membership in a number of
      committees. He holds over 30 patents and patent applications in the areas of
      vaccines, tumor antigens and monoclonal antibodies and has received honors and
      awards throughout his career. Jeffrey Schlom has been involved in translational
      research involving the immunotherapy of a range of carcinomas and predominantly
      works in the areas of tumor immunology, mechanisms of tumor cell-immune cell
      interactions and immune mechanisms. He has recently been working on the design
      and characterization of recombinant vaccines for cancer therapy. 

PMID- 24098991
TI  - Reduction of 4-styrylpyridine by SmI2: an inner sphere electron tranfer case
      where the binding site differs from the reaction center.
AB  - In the reduction of 4-styrylpyridine by SmI2, the binding site for SmI2 differs
      from the reaction center. MeOH and TFE exhibit an unprecedented behavior showing
      a sigmoidic effect on the reaction rate, which levels off around 0.5-1 M. The
      reactions display autocatalytic behavior and a U shape dependence of the reaction
      rate on the HMPA concentration. With high likelihood, the reactions involve a
      proton coupled electron transfer step. 

PMID- 24098992
TI  - Fiber intake and risk of nasopharyngeal carcinoma: a case-control study.
AB  - Some studies examined the inverse relation between nasopharyngeal carcinoma (NPC)
      risk and dietary fibers in endemic populations. By means of a hospital-based case
      control study, we verified whether this association was also present in Italy in
      connection with various types of dietary fibers. Cases were 198 patients with
      incident, histologically confirmed, NPC admitted to major teaching and general
      hospitals during 1992-2008. Controls were 594 patients admitted for acute,
      nonneoplastic conditions to the same hospital network of cases. Information was
      elicited using a validated food frequency questionnaire including 78 foods, food
      groups, or dishes. Odds ratios (OR) and corresponding 95% confidence intervals
      (CI) were estimated for quartiles of intake of different types of fiber after
      allowance for energy intake and other potential confounding factors. Total fiber
      intake was inversely related to risk of NPC (OR = 0.58 for the highest vs. the
      lowest quartile of intake; 95% CI: 0.34-0.96). We found an inverse association
      for total soluble (OR = 0.58; 95% CI: 0.35-0.96) and total insoluble fiber (OR =
      0.56; 95% CI: 0.33-0.95), in particular cellulose (OR = 0.57; 95% CI: 0.33-0.96),
      and lignin (OR = 0.51; 95% CI: 0.31-0.85). In conclusion, this study suggests
      that dietary intake of soluble and insoluble fibers is inversely related to NPC
      risk in a nonendemic southern population. 

PMID- 24098993
TI  - Service provision for people with learning disability.

PMID- 24098994
TI  - The contribution of sex to clinical picture variability.

PMID- 24098995
TI  - Minor neurological dysfunction and behaviour in 9-year-old children born at term:
      evidence for sex dimorphism.
AB  - AIM: The aim of the study was to assess associations between minor neurological
      dysfunction (MND) and behaviour, with specific attention to sex differences.
      METHOD: This was an observational cohort study in which 341 9-year-old children
      (177 male, 164 female) without perinatal risk were neurologically assessed, with
      attention to severity and type of MND. Eight domains of dysfunction were
      distinguished, including posture and muscle tone, fine manipulative ability and
      coordination. Severity of MND was based on the number of dysfunctional domains.
      Behaviour was assessed by parents and teachers using the Child Behavior Checklist
      and Teacher's Report Form (TRF); outcomes were internalizing and externalizing
      behaviour and total score of behavioural problems. RESULTS: Females with complex
      MND or dysfunctional posture and muscle tone had increased risk for externalizing
      behavioural problems (OR 4.52, 95% CI 1.01-20.2, and OR 4.05, 95% CI 1.06-15.5,
      respectively). In males, these associations were absent. However, males with
      simple MND had an increased risk for behavioural problems indicated by the total
      TRF-score (OR 7.52, 95% CI 1.36-41.4). INTERPRETATION: In children without
      perinatal risk, associations between MND and behaviour are sex-specific. In
      females, dysfunction of complex neural networks, including the cerebellum, is
      associated with externalizing behaviour. In males, neurobehavioural relationships
      are limited, suggesting a larger role of psychosocial factors in the genesis of
      behavioural problems.

PMID- 24098996
TI  - Students benefit from developing their own emergency medicine OSCE stations: a
      comparative study using the matched-pair method.
AB  - BACKGROUND: Students can improve the learning process by developing their own
      multiple choice questions. If a similar effect occurred when creating OSCE
      (objective structured clinical examination) stations by themselves it could be
      beneficial to involve them in the development of OSCE stations. This study
      investigates the effect of students developing emergency medicine OSCE stations
      on their test performance. METHOD: In the 2011/12 winter semester, an emergency
      medicine OSCE was held for the first time at the Faculty of Medicine at the
      University of Leipzig. When preparing for the OSCE, 13 students (the intervention
      group) developed and tested emergency medicine examination stations as a learning
      experience. Their subsequent OSCE performance was compared to that of 13 other
      students (the control group), who were parallelized in terms of age, gender,
      semester and level of previous knowledge using the matched-pair method. In
      addition, both groups were compared to 20 students who tested the OSCE prior to
      regular emergency medicine training (test OSCE group). RESULTS: There were no
      differences between the three groups regarding age (24.3 +/- 2.6; 24.2 +/- 3.4
      and 24 +/- 2.3 years) or previous knowledge (29.3 +/- 3.4; 29.3 +/- 3.2 and 28.9
      +/- 4.7 points in the multiple choice [MC] exam in emergency medicine). Merely
      the gender distribution differed (8 female and 5 male students in the
      intervention and control group vs. 3 males and 17 females in the test OSCE
      group).In the exam OSCE, participants in the intervention group scored 233.4 +/-
      6.3 points (mean +/- SD) compared to 223.8 +/- 9.2 points (p < 0.01) in the
      control group. Cohen's effect size was d = 1.24. The students of the test OSCE
      group scored 223.2 +/- 13.4 points. CONCLUSIONS: Students who actively develop
      OSCE stations when preparing for an emergency medicine OSCE achieve better exam
      results.

PMID- 24098999
TI  - Memantine transport across the mouse blood-brain barrier is mediated by a
      cationic influx H+ antiporter.
AB  - Memantine (MEM) is prescribed in mono and combination therapies for treating the
      symptoms of moderate to severe Alzheimer's disease (AD). Despite MEM being widely
      prescribed with other AD and non-AD medicines, very little is known about its
      mechanism of transport across the blood-brain barrier (BBB), and whether the
      nature of this transport lends MEM to a potential for drug-drug interactions at
      the BBB. Therefore, the purpose of this study was to characterize the mechanisms
      facilitating MEM brain uptake in Swiss Outbred mice using an in situ transcardiac
      perfusion technique, and identify the putative transporter involved in MEM
      disposition into the brain. Following transcardiac perfusion of MEM with
      increasing concentrations, the brain uptake of MEM was observed to be saturable.
      Furthermore, MEM brain uptake was reduced (up to 55%) by various cationic
      transporter inhibitors (amantadine, quinine, tetraethylammonium, choline and
      carnitine) and was dependent on extracellular pH, while being independent of
      membrane depolarization and the presence of Na(+) in the perfusate. In addition,
      MEM brain uptake was observed to be sensitive to changes in intracellular pH,
      hence, likely to be driven by H(+)/MEM antiport mechanisms. Taken together, these
      findings implicate the involvement of an organic cation transporter regulated by
      proton antiport mechanisms in the transport of MEM across the mouse BBB, possibly
      the organic cation/carnitine transporter, OCTN1. These studies also clearly
      demonstrate the brain uptake of MEM is significantly reduced by other cationic
      compounds, highlighting the need to consider the possibility of drug interactions
      with MEM at the BBB, potentially leading to reduced brain uptake and, therefore,
      altered efficacy of MEM when used in patients on multidrug regimens. 

PMID- 24099001
TI  - Stabilization of a ruthenium(II) polypyridyl dye on nanocrystalline TiO2 by an
      electropolymerized overlayer.
AB  - The long-term performance of dye-sensitized solar and photoelectrochemical cells
      is strongly dependent on the stability of surface-bound chromophores and
      chromophore-catalyst assemblies at metal oxide interfaces. We report here
      electropolymerization as a strategy for increasing interfacial stability and as a
      simple synthetic route for preparing spatially controlled, multicomponent films
      at an interface. We demonstrate that [Fe(v-tpy)2](2+) (v-tpy = 4'-vinyl
      2,2':6',2"-terpyridine) can be reductively electropolymerized on nanocrystalline
      TiO2 functionalized with a phosphonate-derivatized Ru(II) polypyridyl
      chromophore. The outer:inner Fe:Ru ratio can be controlled by the number of
      reductive electrochemical scan cycles as shown by UV-visible absorption and
      energy dispersive X-ray spectroscopy measurements. Overlayer
      electropolymerization results in up to 30-fold enhancements in photostability
      compared to the surface-bound dye alone. Transient absorbance measurements have
      been used to demonstrate that photoexcitation and electron injection by the MLCT
      excited state(s) of the surface-bound Ru(II) complex is followed by directional,
      outside-to-inside, Fe(II) -> Ru(III) electron transfer. This strategy is
      appealing in opening a new approach for synthesizing surface-stabilized
      chromophore-catalyst assemblies on nanocrystalline metal oxide films. 

PMID- 24099000
TI  - Computational approaches for discovery of common immunomodulators in fungal
      infections: towards broad-spectrum immunotherapeutic interventions.
AB  - BACKGROUND: Fungi are the second most abundant type of human pathogens. Invasive
      fungal pathogens are leading causes of life-threatening infections in clinical
      settings. Toxicity to the host and drug-resistance are two major deleterious
      issues associated with existing antifungal agents. Increasing a host's tolerance
      and/or immunity to fungal pathogens has potential to alleviate these problems. A
      host's tolerance may be improved by modulating the immune system such that it
      responds more rapidly and robustly in all facets, ranging from the recognition of
      pathogens to their clearance from the host. An understanding of biological
      processes and genes that are perturbed during attempted fungal exposure,
      colonization, and/or invasion will help guide the identification of endogenous
      immunomodulators and/or small molecules that activate host-immune responses such
      as specialized adjuvants. RESULTS: In this study, we present computational
      techniques and approaches using publicly available transcriptional data sets, to
      predict immunomodulators that may act against multiple fungal pathogens. Our
      study analyzed data sets derived from host cells exposed to five fungal
      pathogens, namely, Alternaria alternata, Aspergillus fumigatus, Candida albicans,
      Pneumocystis jirovecii, and Stachybotrys chartarum. We observed statistically
      significant associations between host responses to A. fumigatus and C. albicans.
      Our analysis identified biological processes that were consistently perturbed by
      these two pathogens. These processes contained both immune response-inducing
      genes such as MALT1, SERPINE1, ICAM1, and IL8, and immune response-repressing
      genes such as DUSP8, DUSP6, and SPRED2. We hypothesize that these genes belong to
      a pool of common immunomodulators that can potentially be activated or suppressed
      (agonized or antagonized) in order to render the host more tolerant to infections
      caused by A. fumigatus and C. albicans. CONCLUSIONS: Our computational approaches
      and methodologies described here can now be applied to newly generated or
      expanded data sets for further elucidation of additional drug targets. Moreover,
      identified immunomodulators may be used to generate experimentally testable
      hypotheses that could help in the discovery of broad-spectrum immunotherapeutic
      interventions. All of our results are available at the following supplementary
      website: http://bioinformatics.cs.vt.edu/~murali/supplements/2013-kidane-bmc.

PMID- 24099003
TI  - A fast growing spectrum of biological functions of gamma-secretase in development
      and disease.
AB  - gamma-secretase, which assembles as a tetrameric complex, is an aspartyl protease
      that proteolytically cleaves substrate proteins within their membrane-spanning
      domain; a process also known as regulated intramembrane proteolysis (RIP). RIP
      regulates signaling pathways by abrogating or releasing signaling molecules.
      Since the discovery, already >15 years ago, of its catalytic component,
      presenilin, and even much earlier with the identification of amyloid precursor
      protein as its first substrate, gamma-secretase has been commonly associated with
      Alzheimer's disease. However, starting with Notch and thereafter a continuously
      increasing number of novel substrates, gamma-secretase is becoming linked to an
      equally broader range of biological processes. This review presents an updated
      overview of the current knowledge on the diverse molecular mechanisms and
      signaling pathways controlled by gamma-secretase, with a focus on organ
      development, homeostasis and dysfunction. This article is part of a Special Issue
      entitled: Intramembrane Proteases.

PMID- 24099002
TI  - Function of site-2 proteases in bacteria and bacterial pathogens.
AB  - Site-2 proteases (S2Ps) are a class of intramembrane metalloproteases named after
      the founding member of this protein family, human S2P, which control cholesterol
      and fatty acid biosynthesis by cleaving Sterol Regulatory Element Binding
      Proteins which control cholesterol and fatty acid biosynthesis. S2Ps are widely
      distributed in bacteria and participate in diverse pathways that control such
      diverse functions as membrane integrity, sporulation, lipid biosynthesis,
      pheromone production, virulence, and others. The most common signaling mechanism
      mediated by S2Ps is the coupled degradation of transmembrane anti-Sigma factors
      to activate ECF Sigma factor regulons. However, additional signaling mechanisms
      continue to emerge as more prokaryotic S2Ps are characterized, including direct
      proteolysis of membrane embedded transcription factors and proteolysis of non
      transcriptional membrane proteins or membrane protein remnants. In this review we
      seek to comprehensively review the functions of S2Ps in bacteria and bacterial
      pathogens and attempt to organize these proteases into conceptual groups that
      will spur further study. This article is part of a Special Issue entitled:
      Intramembrane Proteases. 

PMID- 24099004
TI  - Mechanism, specificity, and physiology of signal peptide peptidase (SPP) and SPP
      like proteases.
AB  - Signal peptide peptidase (SPP) and the homologous SPP-like (SPPL) proteases
      SPPL2a, SPPL2b, SPPL2c and SPPL3 belong to the family of GxGD intramembrane
      proteases. SPP/SPPLs selectively cleave transmembrane domains in type II
      orientation and do not require additional co-factors for proteolytic activity.
      Orthologues of SPP and SPPLs have been identified in other vertebrates, plants,
      and eukaryotes. In line with their diverse subcellular localisations ranging from
      the ER (SPP, SPPL2c), the Golgi (SPPL3), the plasma membrane (SPPL2b) to
      lysosomes/late endosomes (SPPL2a), the different members of the SPP/SPPL family
      seem to exhibit distinct functions. Here, we review the substrates of these
      proteases identified to date as well as the current state of knowledge about the
      physiological implications of these proteolytic events as deduced from in vivo
      studies. Furthermore, the present knowledge on the structure of intramembrane
      proteases of the SPP/SPPL family, their cleavage mechanism and their substrate
      requirements are summarised. This article is part of a Special Issue entitled:
      Intramembrane Proteases. 

PMID- 24099005
TI  - Untangling structure-function relationships in the rhomboid family of
      intramembrane proteases.
AB  - Rhomboid proteases are a family of integral membrane proteins that have been
      implicated in critical regulatory roles in a wide array of cellular processes and
      signaling events. The determination of crystal structures of the prokaryotic
      rhomboid GlpG from Escherichia coli and Haemophilus influenzae has ushered in an
      era of unprecedented understanding into molecular aspects of intramembrane
      proteolysis by this fascinating class of protein. A combination of structural
      studies by X-ray crystallography, and biophysical and spectroscopic analyses,
      combined with traditional enzymatic and functional analysis has revealed
      fundamental aspects of rhomboid structure, substrate recognition and the
      catalytic mechanism. This review summarizes these remarkable advances by
      examining evidence for the proposed catalytic mechanism derived from inhibitor co
      crystal structures, conflicting models of rhomboid-substrate interaction, and
      recent work on the structure and function of rhomboid cytosolic domains. In
      addition to exploring progress on aspects of rhomboid structure, areas for future
      research and unaddressed questions are emphasized and highlighted. This article
      is part of a Special Issue entitled: Intramembrane Proteases. 

PMID- 24099006
TI  - Biochemical and structural insights into intramembrane metalloprotease
      mechanisms.
AB  - Intramembrane metalloproteases are nearly ubiquitous in living organisms and they
      function in diverse processes ranging from cholesterol homeostasis and the
      unfolded protein response in humans to sporulation, stress responses, and
      virulence of bacteria. Understanding how these enzymes function in membranes is a
      challenge of fundamental interest with potential applications if modulators can
      be devised. Progress is described toward a mechanistic understanding, based
      primarily on molecular genetic and biochemical studies of human S2P and bacterial
      SpoIVFB and RseP, and on the structure of the membrane domain of an archaeal
      enzyme. Conserved features of the enzymes appear to include transmembrane helices
      and loops around the active site zinc ion, which may be near the membrane
      surface. Extramembrane domains such as PDZ (PSD-95, DLG, ZO-1) or CBS
      (cystathionine-beta-synthase) domains govern substrate access to the active site,
      but several different mechanisms of access and cleavage site selection can be
      envisioned, which might differ depending on the substrate and the enzyme. More
      work is needed to distinguish between these mechanisms, both for enzymes that
      have been relatively well-studied, and for enzymes lacking PDZ and CBS domains,
      which have not been studied. This article is part of a Special Issue entitled:
      Intramembrane Proteases. 

PMID- 24099009
TI  - The mitochondrial rhomboid protease: its rise from obscurity to the pinnacle of
      disease-relevant genes.
AB  - The Rhomboid proteases belong to a highly conserved family of proteins that are
      present in all branches of life. In Drosophila, the secretory pathway-localized
      rhomboid proteases are crucial for epidermal growth factor (EGF) signaling. The
      identification of a mitochondrial-localized rhomboid protease shed light on other
      functions of rhomboid proteases including the maintenance of mitochondrial
      morphology and the regulation of apoptosis. More recent work has revealed other
      functions of the mitochondrial rhomboid protease in mitochondrial and cellular
      biology, failure of which have been implicated in human diseases. In this review,
      we will summarize the current knowledge and disease relevance of the
      mitochondrial-localized rhomboid protease. This article is part of a Special
      Issue entitled: Intramembrane Proteases. 

PMID- 24099007
TI  - Toward the structure of presenilin/gamma-secretase and presenilin homologs.
AB  - Presenilin is the catalytic component of the gamma-secretase complex, a membrane
      embedded aspartyl protease that plays a central role in biology and in the
      pathogenesis of Alzheimer's disease. Upon assembly with its three protein
      cofactors (nicastrin, Aph-1 and Pen-2), presenilin undergoes autoproteolysis into
      two subunits, each of which contributes one of the catalytic aspartates to the
      active site. A family of presenilin homologs, including signal peptide peptidase,
      possess proteolytic activity without the need for other protein factors, and
      these simpler intramembrane aspartyl proteases have given insight into the action
      of presenilin within the gamma-secretase complex. Cellular and molecular studies
      support a nine-transmembrane topology for presenilins and their homologs, and
      small-molecule inhibitors and cysteine scanning with crosslinking have suggested
      certain presenilin residues and regions that contribute to substrate recognition
      and handling. Identification of partial complexes has also offered clues to
      protein-protein interactions within the gamma-secretase complex. Biophysical
      methods have allowed 3D views of the gamma-secretase complex and presenilins.
      Most recently, the crystal structure of a microbial presenilin homolog has
      confirmed a nine-transmembrane topology and intramembranous location and
      proximity of the two conserved and essential aspartates. The crystal structure
      also provides a platform for the formulation of specific hypotheses regarding
      substrate interaction and catalysis as well as the pathogenic mechanism of
      Alzheimer-causing presenilin mutations. This article is part of a Special Issue
      entitled: Intramembrane Proteases.

PMID- 24099008
TI  - The roles of intramembrane proteases in protozoan parasites.
AB  - Intramembrane proteolysis is widely conserved throughout different forms of life,
      with three major types of proteases being known for their ability to cleave
      peptide bonds directly within the transmembrane domains of their substrates.
      Although intramembrane proteases have been extensively studied in humans and
      model organisms, they have only more recently been investigated in protozoan
      parasites, where they turn out to play important and sometimes unexpected roles.
      Signal peptide peptidases are involved in endoplasmic reticulum (ER) quality
      control and signal peptide degradation from exported proteins. Recent studies
      suggest that repurposing inhibitors developed for blocking presenilins may be
      useful for inhibiting the growth of Plasmodium, and possibly other protozoan
      parasites, by blocking signal peptide peptidases. Rhomboid proteases, originally
      described in the fly, are also widespread in parasites, and are especially
      expanded in apicomplexans. Their study in parasites has revealed novel roles that
      expand our understanding of how these proteases function. Within this diverse
      group of parasites, rhomboid proteases contribute to processing of adhesins
      involved in attachment, invasion, intracellular replication, phagocytosis, and
      immune evasion, placing them at the vertex of host-parasite interactions. This
      article is part of a Special Issue entitled: Intramembrane Proteases. 

PMID- 24099011
TI  - Emerging roles for diverse intramembrane proteases in plant biology.
AB  - Progress in the field of regulated intramembrane proteolysis (RIP) in recent
      years has made its impact on plant biology as well. Although this field within
      plant research is still in its infancy, some interesting observations have
      started to emerge. Gene encoding orthologs of rhomboid proteases, site-2
      proteases (S2P), presenilin/gamma-secretases, and signal peptide peptidases are
      found in plant genomes and some of these gene products were identified in
      different plant cell membranes. The lack of chloroplast-located rhomboid
      proteases was associated with reduced fertility and aberrations in flower
      morphology. Mutations in homologues of S2P resulted in chlorophyll deficiency and
      impaired chloroplast development. An S2P was also implicated in the response to
      ER stress through cleavage of ER-membrane bZIP transcription factors, allowing
      their migration to the nucleus and activation of the transcription of BiP
      chaperones. Other membrane-bound transcription factors of the NAC and PHD
      families were also demonstrated to undergo RIP and relocalization to the nucleus.
      These and other new data are expected to shed more light on the roles of
      intramembrane proteases in plant biology in the future. This article is part of a
      Special Issue entitled: Intramembrane Proteases. 

PMID- 24099010
TI  - Roles of regulated intramembrane proteolysis in virus infection and antiviral
      immunity.
AB  - Regulated intramembrane proteolysis (RIP) is a signaling mechanism through which
      transmembrane precursor proteins are cleaved to liberate their cytoplasmic and/or
      luminal/extracellular fragments from membranes so that these fragments are able
      to function at a new location. Recent studies have indicated that this
      proteolytic reaction plays an important role in host-virus interaction. On one
      hand, RIP transfers the signal from the endoplasmic reticulum (ER) to nucleus to
      activate antiviral genes in response to alteration of the ER caused by viral
      infection. On the other hand, RIP can be hijacked by virus to process
      transmembrane viral protein precursors and to destroy transmembrane antiviral
      proteins. Understanding this Yin and Yang side of RIP may lead to new strategies
      to combat viral infection. This article is part of a Special Issue entitled:
      Intramembrane Proteases. 

PMID- 24099012
TI  - Gold(I)-catalyzed cascade approach for the synthesis of tryptamine-based
      polycyclic privileged scaffolds as alpha1-adrenergic receptor antagonists.
AB  - An efficient and facile gold(I)-catalyzed one-pot cascade protocol has been
      developed for the synthesis of tryptamine-fused polycyclic privileged structures
      through the treatment of substituted tryptamines and 2-ethynylbenzoic acids or 2
      ethynylphenylacetic acids. This strategy features the formation of one C-C bond
      and two C-N bonds with high yields and broad substrate tolerance. The selected
      reduced target molecules are validated to perform as alpha1-adrenergic receptors
      antagonists. The most potent one, 4bh, exhibits an IC50 value of 277 nM on
      alpha1A subtype with a selectivity ratio of 15.8 over alpha1B subtype. 

PMID- 24099013
TI  - Dangerous snakes, deadly snakes and medically important snakes.
AB  - This correspondence argues that the dangerousness of a venomous snake species is
      not solely determined by the venom characteristics or the lethality of the snake,
      and recognizes that medical importance comprises a key variable as well. The
      medical importance of a snake is determined by several factors - including
      frequency of medical attention after a bite, local or systemic envenomation
      provoked by the bite, fatal bites, long term consequences, availability of
      antivenom therapy as well as the size of the population at risk - that may vary
      from one region to another. 

PMID- 24099015
TI  - Drug-induced cholestasis.
AB  - Drug-induced cholestasis manifests as an acute self-limiting injury or as a
      chronic perpetuating injury, resulting in duct loss and cirrhosis. The number of
      drugs implicated in drug-induced cholestasis grows every year as new drugs are
      developed and approved. Other agents such as herbals, nutritional supplements,
      and complementary and alternative medicines are also reported to cause
      cholestatic liver injury. Recent literature on molecular transporters involved in
      bile transport has improved our understanding of patterns of drug-induced liver
      injury and the mechanisms of cholestasis. This article summarizes the probable
      offending drugs, and the diagnosis and management of drug-induced cholestasis. 

PMID- 24099014
TI  - Mechanisms of drug-induced liver injury.
AB  - Drug-induced liver injury (DILI) represents a broad spectrum of liver
      manifestations. However, the most common manifestation is hepatocyte death
      following drug intake. DILI can be predictable and dose dependent with a notable
      example of acetaminophen toxicity. Idiosyncratic DILI occurs in an unpredictable
      fashion at low frequencies, implying that environmental and genetic factors alter
      the susceptibility of individuals to the insult (drugs). 

PMID- 24099017
TI  - Histopathologic manifestations of drug-induced hepatotoxicity.
AB  - Drug-induced hepatotoxicity is underrecognized but increasingly identified as
      causing acute and chronic liver disease. Several prescription drugs, over-the
      counter medications, dietary and/or supplementary agents, and herbal products are
      hepatotoxic. Drug-induced liver injury mimics other primary acute and chronic
      liver diseases and it should be considered in patients with hepatobiliary
      disease. Certain drugs result in specific histopathologic patterns of liver
      injury, which may help in sorting out the responsible drug. The diagnosis of drug
      induced hepatotoxicity is challenging. It involves excluding other possible
      causes, careful medication history, the latent period between drug exposure and
      symptom onset and/or abnormal liver tests, and histopathologic findings. 

PMID- 24099016
TI  - Drug-induced steatohepatitis.
AB  - Nonalcoholic fatty liver disease (NAFLD) is currently the most common cause of
      chronic liver disease in the United States. The term NALFD was first used by
      Ludwig in 1980 to describe the presence of hepatic steatosis and steatohepatitis
      in a series of patients with no identifiable cause. Since then, our insight into
      the pathogenesis of NAFLD has expanded significantly. We now know that NAFLD is
      closely related to metabolic syndrome and chronic low-grade inflammation. In the
      following review, the authors summarize the current evidence about drugs that
      lead to hepatic steatosis and steatohepatitis and pathogenic mechanisms thereof. 

PMID- 24099018
TI  - Clinical manifestations and treatment of drug-induced hepatotoxicity.
AB  - With an increase of prescription medication and herbal supplement use, drug
      induced liver injury (DILI) has become an increasingly important entity. Because
      DILI is a usually readily treatable condition, it is essential for providers to
      reach a diagnosis in a timely fashion. Unfortunately, varied clinical
      presentations, difficulties in establishing causality, and lack of a gold
      standard diagnostic criterion may make early diagnosis difficult. This article
      seeks to define commonly used terminology, describe common clinical presentations
      of DILI, provide an overview of current diagnostic criteria, and provide
      management guidelines. 

PMID- 24099019
TI  - Drug-induced acute liver failure.
AB  - Although acute liver failure caused by drug-induced liver injury comprises a
      small fraction of overall drug-induced liver injury, these patients require high
      resource use and have relatively poor outcomes. Drug-induced liver injury caused
      by idiosyncrasy more often leads to death or transplantation than does
      acetaminophen acute liver failure, but the number of patients in each category
      receiving a graft is roughly the same. Efforts in the future to improve outcomes
      should focus on more effective treatments and better methods to identify those
      that might experience poor outcomes. 

PMID- 24099020
TI  - Acetaminophen-related hepatotoxicity.
AB  - Acetaminophen (APAP) is the leading worldwide cause of drug overdose and acute
      liver failure (ALF). Single overdose ingestion and therapeutic misadventure may
      cause hepatotoxicity. Several factors, such as concomitant alcohol use or abuse,
      concurrent medications, genetic factors, and nutritional status, can influence
      the susceptibility and severity of APAP hepatotoxicity. Early manifestations of
      APAP hepatotoxicity are nonspecific, but require prompt recognition by
      physicians. Patients with repeated overdose tend to present late, and in such
      hepatotoxicity may have already evolved. N-acetylcysteine is a very effective
      antidote when giving within 8 hours, and is also recommended after a presentation
      of hepatotoxicity and ALF. The prognosis of patients with APAP-induced ALF is
      better than other causes of ALF. Liver transplantation should be offered to those
      who are unlikely to survive. 

PMID- 24099021
TI  - Hepatotoxicity of antibiotics: a review and update for the clinician.
AB  - Collectively, the various classes of antibiotics are a leading cause of drug
      induced liver injury (DILI). However, acute antibiotic-associated DILI can be
      difficult to diagnose, as the course of therapy is usually brief, and other
      confounding factors are often present. In addition to the broad clinicopathologic
      spectrum of hepatotoxicity associated with the antimicrobials, the underlying
      infectious disease being treated may itself be associated with hepatic
      dysfunction and jaundice. This review provides summarized information on several
      classes of antimicrobial agents, highlighting new agents causing DILI and
      updating information on older agents. 

PMID- 24099022
TI  - Nonsteroidal anti-inflammatory drug-induced hepatoxicity.
AB  - Nonsteroidal anti-inflammatory drugs are among the most prescribed medications
      worldwide. After antibiotics and anticonvulsants they are considered the most
      common medications associated with drug-induced liver injury mainly through an
      idiosyncratic form of hepatotoxicity. In rare cases severe hepatotoxicity has
      been described with significant morbidity and mortality. Genetic risk factors
      have been reported with diclofenac and lumiracoxib. Postmarketing surveillance
      and monitoring is crucial to identify severe cases of hepatotoxicity. 

PMID- 24099023
TI  - Antiretroviral and anti-hepatitis C virus direct-acting antiviral-related
      hepatotoxicity.
AB  - Antiretroviral-related hepatotoxicity occurs commonly in patients with human
      immunodeficiency virus (HIV). Liver injury ranges from unconjugated
      hyperbilirubinemia and nodular regenerative hyperplasia to lactic acidosis and
      toxic hepatitis. Effective antiretroviral therapy has changed coinfected
      patients' primary morbidities and mortality to chronic liver disease rather than
      complications from HIV. Treatment for hepatitis C virus (HCV) is strongly
      encouraged early in all coinfected patients. However, drug-drug interactions must
      be considered to ensure safe and tolerable use alone or in combination with
      antiretroviral therapies. The first-generation and newer HCV direct-acting
      antivirals are promising in coinfected patients, with minimal side effects and
      hepatotoxicity. 

PMID- 24099024
TI  - Chemotherapy-induced hepatotoxicity.
AB  - Most hepatotoxicity secondary to chemotherapy is idiosyncratic and, therefore,
      neither dose dependent nor predictable. Some chemotherapy is cleared by the liver
      and requires dose adjustment in the face of significant liver dysfunction. In
      addition, preexisting abnormal liver function has been shown to increase the risk
      of hepatotoxicity. In addition to typical hepatocellular injury, other
      presentations, including cholestasis and hepatic sinusoidal obstruction syndrome,
      also commonly occur. The outcomes can range from asymptomatic liver function test
      abnormalities, which resolve spontaneously, to cirrhosis, which occurs despite
      discontinuation of the chemotherapeutic agent. 

PMID- 24099025
TI  - Drug-induced liver injury from antiepileptic drugs.
AB  - Drug-induced liver injury is a potential complication of innumerable medications.
      Most cases do not occur in a predictable, dose-dependent manner, leading to
      delayed recognition of a drug's hepatotoxic potential until after its release
      into the market. The estimated occurrence is 1 in 10,000 to 100,000 patients.
      However, the rates are likely higher because many cases go unrecognized owing to
      lack of reporting or missed diagnosis. This article reviews the most commonly
      associated antiepileptic drugs. 

PMID- 24099026
TI  - Lipid-lowering agents and hepatotoxicity.
AB  - Lipid-lowering therapy is increasingly being used in patients for a variety of
      diseases, the most important being secondary prevention of cardiovascular
      disease. Many lipid-lowering drugs carry side effects that include elevations in
      hepatic function tests and liver toxicity. In many cases, these drugs are not
      prescribed or they are underprescribed because of fears of injury to the liver.
      This article attempts to review key trials with respect to the hepatotoxicity of
      these drugs. Recommendations are also provided with respect to the selection of
      low-risk patients and strategies to lower the risk of hepatotoxicity when
      prescribing these medications. 

PMID- 24099027
TI  - Liver injury induced by herbal complementary and alternative medicine.
AB  - Herbal and dietary supplement use is common. Most marketed products consist of
      complex mixtures. Although they are perceived as safe, instances of
      hepatotoxicity attributable to these products underscore their potential for
      injury, but the exact component that is responsible for injury is difficult to
      discern. The lenient regulatory environment in the United States, which opens the
      possibility of adulteration and contamination, adds to the challenge of disease
      attribution. Although many different herbal and dietary supplements have been
      reported to cause liver injury, in the United States, products used for
      bodybuilding and weight loss are the most commonly implicated. 

PMID- 24099028
TI  - Hepatotoxicity and drug interactions in liver transplant candidates and
      recipients.
AB  - In this article the medications that have been shown to increase rates of drug
      induced liver injury in patients with cirrhosis and the important drug-drug
      interactions in recipients of liver transplantation are reviewed. In general, the
      risk of drug-induced liver injury in patients with cirrhosis does not seem to be
      higher when compared with the noncirrhotic population. There are, however, 2
      classes of agents that have been implicated-medications used to treat
      tuberculosis and medications used to treat human immunodeficiency virus
      infection. However, with careful monitoring, even significant interactions can be
      effectively managed. 

PMID- 24099029
TI  - How to avoid being surprised by hepatotoxicity at the final stages of drug
      development and approval.
AB  - Drugs that caused severe drug-induced live injury (DILI) in humans have typically
      not shown clear hepatotoxic signals in preclinical assessment. However, clinical
      trial databases may show evidence of a drug's potential for severe DILI if
      clinical and laboratory data are evaluated for evidence of milder liver injury.
      The most specific indicator during a clinical trial for a drug's potential to
      cause severe DILI is occurrence of cases of drug induced hepatocellular injury
      accompanied by altered liver function (eg, elevated direct bilirubin). Meticulous
      causality assessment of hepatic cases and strict adherence to hepatic
      discontinuation rules are critical components of this approach. 

PMID- 24099030
TI  - The art and science of medicine is evolving along with technology. Preface.

PMID- 24099031
TI  - Rapid determination of total conjugated linoleic acid content in select Canadian
      cheeses by (1)h NMR spectroscopy.
AB  - The application of (1)H nuclear magnetic resonance (NMR) spectroscopy to the
      measurement of conjugated linoleic acid (CLA) content in the lipid fraction of
      dairy products is both a novel and inviting alternative to traditional methods
      such as gas chromatography (GC), which can require time-consuming sample
      derivatization. In this work, a newly developed, rapid, and reliable lipid
      extraction protocol was combined with simple, nondestructive (1)H NMR
      spectroscopic analysis to measure the total CLA content in CLA standards and in
      various Canadian cheeses from conventional, organic, and grass-fed dairy sources.
      The total CLA concentrations (mg/g cheese) obtained using these new extraction
      and analysis methods were consistent with amounts found using the modified Folch
      extraction and GC analysis (correlation coefficient of 0.948). Results showed
      that cheeses from exclusively grass-fed dairy cows were significantly higher in
      total CLA content than either conventional or organic cheese. 

PMID- 24099032
TI  - What have we learnt so far about child and adolescent restraint in our health and
      social care services?

PMID- 24099033
TI  - New bio-ceramization processes applied to vegetable hierarchical structures for
      bone regeneration: an experimental model in sheep.
AB  - Bone loss is still a major problem in orthopedics. The purpose of this
      experimental study is to evaluate the safety and regenerative potential of a new
      scaffold based on a bio-ceramization process for bone regeneration in long
      diaphyseal defects in a sheep model. The scaffold was obtained by transformation
      of wood pieces into porous biomorphic silicon carbide (BioSiC(r)). The process
      enabled the maintenance of the original wood microstructure, thus exhibiting
      hierarchically organized porosity and high mechanical strength. To improve cell
      adhesion and osseointegration, the external surface of the hollow cylinder was
      made more bioactive by electrodeposition of a uniform layer of collagen fibers
      that were mineralized with biomimetic hydroxyapatite, whereas the internal part
      was filled with a bio-hybrid HA/collagen composite. The final scaffold was then
      implanted in the metatarsus of 15 crossbred (Merinos-Sarda) adult sheep, divided
      into 3 groups: scaffold alone, scaffold with platelet-rich plasma (PRP)
      augmentation, and scaffold with bone marrow stromal cells (BMSCs) added during
      implantation. Radiological analysis was performed at 4, 8, 12 weeks, and 4
      months, when animals were sacrificed for the final radiological, histological,
      and histomorphometric evaluation. In all tested treatments, these analyses
      highlighted the presence of newly formed bone at the bone scaffolds' interface.
      Although a lack of substantial effect of PRP was demonstrated, the scaffold+BMSC
      augmentation showed the highest value of bone-to-implant contact and new bone
      growth inside the scaffold. The findings of this study suggest the potential of
      bio-ceramization processes applied to vegetable hierarchical structures for the
      production of wood-derived bone scaffolds, and document a suitable augmentation
      procedure in enhancing bone regeneration, particularly when combined with BMSCs.

PMID- 24099034
TI  - Prelacteal feeding practices in Vietnam: challenges and associated factors.
AB  - BACKGROUND: Despite the importance of early initiation of and exclusive
      breastfeeding, prelacteal feeds continue to pose a barrier to optimal
      breastfeeding practices in several countries, including Vietnam. This study
      examined the factors associated with prelacteal feeding among Vietnamese mothers.
      METHODS: Data from 6068 mother-child (<6 m) dyads were obtained from a cross
      sectional survey conducted in 11 provinces in Vietnam in 2011. Multivariate
      logistic regression analyses were used to examine factors associated with
      prelacteal feeding. RESULTS: During the first three days after birth, 73.3% of
      the newborns were fed prelacteals, 53.5% were fed infants formula, and 44.1% were
      fed water. The odds of feeding prelacteals declined with increased breastfeeding
      knowledge, beliefs about social norms in favor of exclusive breastfeeding, and
      confidence in one's own breastfeeding behaviors. Women who harbored
      misconceptions about breastfeeding had twice the odds of feeding any prelacteals
      (OR: 2.09, 95% CI: 1.74-2.50). Health care factors increasing the odds of
      prelacteal feeding included delivery by caesarean section (OR: 2.94, 95% CI: 2.39
      3.61) or episiotomy (OR: 1.36, 95% CI: 1.17-1.58) and experiencing breastfeeding
      problems (OR: 1.31, 95% CI: 1.04-1.66). Health staff support during pregnancy and
      after birth reduced the odds of feeding formula. However, family support after
      delivery increased the odds of feeding water to newborns. CONCLUSIONS: The
      multiple factors contributing to the high prevalence of prelacteal feeding
      behaviors stress the need for early and appropriate breastfeeding interventions
      in Vietnam, particularly during routine healthcare contacts. Improving
      breastfeeding practices during the first days of an infant's life could be
      achieved by improving knowledge and confidence of mothers through appropriate
      perinatal counseling and support. Ensuring that health facilities integrate these
      practices into routine ante-natal care and post-delivery management is critical.

PMID- 24099035
TI  - Dipeptidyl peptidase IV and its inhibitors: therapeutics for type 2 diabetes and
      what else?
AB  - The proline-specific dipeptidyl aminopeptidase IV (DPP IV, DPP-4, CD26), widely
      expressed in mammalians, releases X-Pro/Ala dipeptides from the N-terminus of
      peptides. DPP IV is responsible of the degradation of the incretin peptide
      hormones regulating blood glucose levels. Several families of DPP IV inhibitors
      have been synthesized and evaluated. Their positive effects on the degradation of
      the incretins and the control of blood glucose levels have been demonstrated in
      biological models and in clinical trials. Presently, several DPP IV inhibitors,
      the "gliptins", are approved for type 2 diabetes or are under clinical
      evaluation. However, the gliptins may also be of therapeutic interest for other
      diseases beyond the inhibition of incretin degradation. In this Perspective, the
      biological functions and potential substrates of DPP IV enzymes are reviewed and
      the characteristics of the DPP IV inhibitors are discussed in view of type 2
      diabetes and further therapeutic interest. 

PMID- 24099036
TI  - Adaptive evolution of the lower jaw dentition in Mexican tetra (Astyanax
      mexicanus).
AB  - BACKGROUND: The Mexican tetra (Astyanax mexicanus) has emerged as a good animal
      model to study the constructive and regressive changes associated with living in
      cave environments, as both the ancestral sighted morph and the cave dwelling
      morph are extant. The cave dwelling morphs lack eyes and body pigmentation, but
      have well developed oral and sensory systems that are essential for survival in
      dark environments. The cave forms and surface forms are interfertile and give
      rise to F1 hybrids progeny known as intermediates. In cavefish, degeneration of
      the lens is one of the key events leading to eye regression. We have previously
      shown that surgical lens removal in surface fish embryos has an effect on the
      craniofacial skeleton. Surprisingly, lens removal was also found to have an
      effect on the caudal teeth in the lower jaw. In order to understand this result,
      we analyzed the lower jaw and upper jaw dentitions of surface, cavefish and F1
      hybrids of surface and cavefish and compared our findings with surface fish that
      underwent lens removal. We also investigated the upper jaw (premaxillae and
      maxillae) dentition in these fish. RESULTS: Our tooth analyses shows that
      cavefish have the highest numbers of teeth in the mandible and maxillae, surface
      forms have the lowest numbers and F1 hybrids are between these groups. These
      differences are not observed in the premaxillae. A wide diversity of cuspal
      morphology can also be found in these fish. Jaw size also differs amongst the
      groups, with the mandible exhibiting the greatest differences. Interestingly,
      tooth number in surgery fish is different only in the caudal region of the
      mandible; this is the region that is constrained in size in all morphs.
      CONCLUSION: Our data provides the first detailed description of the jaw
      dentitions of two morphs of Astyanax mexicanus, as well as in F1 hybrids. Tooth
      number, patterning and cuspal morphology are enhanced in cavefish in all jaws.
      This is in contrast to the increase in tooth number previously observed on the
      lens ablated side of the surgery fish. These findings indicate that the
      mechanisms which govern the constructive traits in cavefish are different to the
      mechanisms causing an increase tooth number in surgery fish.

PMID- 24099037
TI  - Black dog barks at brown fat.
AB  - CRY2 genetic variants associate with the depressive episodes in a range of mood
      disorders. Expression of core clock genes is highly responsive to stimuli in
      brown fat. Brown fat clocks might synchronize clocks in other tissues through
      their control of heat production and core body temperature. Among the repressors
      within the clocks, CRY2 is hypothesized to a key to the resetting of clocks
      throughout and play a leading role in the antidepressant effect of total sleep
      deprivation.

PMID- 24099038
TI  - Clinical review: inferior vena cava filters in the age of patient-centered
      outcomes.
AB  - Inferior vena cava filter (IVCF) use continues to increase in the United States
      (US) despite questionable clinical benefit and increasing concerns over long-term
      complications. For this review we comprehensively examine the randomized,
      prospective data on IVC filter efficacy, compare relative rates of IVCF placement
      in the US and Europe, compare commonly considered guidelines for IVCF
      indications, and the current data on IVCF complications. Searches of MEDLINE and
      Cochrane databases were conducted for randomized prospective IVCF studies. Only
      three randomized prospective studies for IVCFs were identified. Commonly cited
      IVCF guidelines were reviewed with attention to their evolution over time. No
      evidence has shown a survival benefit with IVCF use. Despite this, continued
      rising utilization, especially for primary prophylactic indications, is
      concerning, given increasing evidence of long-term filter-related complications.
      This is particularly noted in the US where IVCF placements for 2012 are projected
      to be 25 times that of an equivalent population in Europe (224,700 versus 9,070).
      Pending much-needed randomized controlled trials that also evaluate long-term
      safety, we support the more stringent American College of Chest Physicians (ACCP)
      guidelines for IVCF placement indications and advocate a close, structured follow
      up of retrievable IVCFs to improve filter retrieval rates.

PMID- 24099039
TI  - Clinical oncology in resource-limited settings.
AB  - Infectious Agents and Cancer is introducing a new section of Clinical Oncology
      with the main objective of stimulating debate through articles published in the
      section. Infectious diseases have been the major causes of morbidity and
      mortality in human populations, and have dominated the medical approach to
      clinical and public health. Successful efforts to control mortality from acute
      infections have paved the way for chronic, mostly indolent, infections to become
      major causes of morbidity. Cancer, hitherto thought to be rare in resource
      limited settings, is becoming a major contributor. The changes in mortality
      patterns are due, in part, to diseases linked to rapid changes in lifestyle,
      urbanization, and pollution. These diseases include many of the non-infection
      associated cancers. However, there is a dearth of information about the burden,
      pathogenesis, and therapeutic approaches about cancer in resource-limited
      countries. There are also substantial other challenges, including economic,
      infrastructure, technology, and personnel. The Journal advocates for interactive
      local-global (lo-bal) efforts to generate relevant knowledge about cancer burden,
      pathogenesis, and therapeutic approaches using a bottom-up approach to sharpen
      the focus on local and global relevance of research and clinical and public
      practice, particularly in resource-limited countries. The section on Clinical
      Oncology in Infectious Agents and Cancer will harness these "lo-bal" strategies
      to reduce substantially the time from concept, discovery, and development and
      implementation of locally and globally applicable diagnostic and therapeutic
      technologies. 

PMID- 24099040
TI  - Fisetin inhibits matrix metalloproteinases and reduces tumor cell invasiveness
      and endothelial cell tube formation.
AB  - Matrix metalloproteinases (MMPs) play an important role in tissue remodeling
      during normal physiological situations and pathological implications such as
      tumor invasion and metastasis. MMP inhibitors were screened from extracts of
      medicinal herbs by an enzymatic assay using the MMP-14 catalytic domain. Among
      samples tested, a methanol extract of the root of Dalbergia odorifera T. CHEN
      (Leguminosae) showed the strongest inhibitory activity. The inhibitory component
      was purified through fractionation methods and identified as fisetin, abundant in
      many fruits and vegetables. In addition to inhibition of MMP-14, fisetin inhibits
      MMP-1, MMP-3, MMP-7, and MMP-9, more efficiently than a naturally occurring MMP
      inhibitor tetracycline. Fisetin dose-dependently inhibits proliferation of
      fibrosarcoma HT-1080 cells and human umbilical vascular endothelial cells
      (HUVECs), MMP-14-mediated activation of proMMP-2 in HT-1080 cells, invasiveness
      of HT-1080 cells, and in vitro tube formation of HUVECs. Therefore, fisetin could
      be valuable as a chemopreventive agent against cancer and a lead compound for
      development of therapeutic MMP inhibitors. 

PMID- 24099042
TI  - Advancing palliative care by learning.

PMID- 24099043
TI  - Mass spectral profiling of glycosaminoglycans from histological tissue surfaces.
AB  - Glycosaminoglycans (GAGs) are found in intracellular granules, cell surfaces, and
      extracellular matrices in a spatially and temporally regulated fashion,
      constituting the environment for cells to interact, migrate, and proliferate.
      Through binding with a great number of proteins, GAGs regulate many facets of
      biological processes from embryonic development to normal physiological
      functions. GAGs have been shown to be involved in pathologic changes and
      immunological responses including cancer metastasis and inflammation. Past
      analyses of GAGs have focused on cell lines, body fluids, and relatively large
      tissue samples. Structures determined from such samples reflect the heterogeneity
      of the cell types present. To gain an understanding of the roles played by GAG
      expression during pathogenesis, it is very important to be able to detect and
      profile GAGs at the histological scale so as to minimize cell heterogeneity to
      potentially inform diagnosis and prognosis. Heparan sulfate (HS) belongs to one
      major class of GAGs, characterized by dramatic structural heterogeneity and
      complexity. To demonstrate feasibility of analysis of HS, 15 MUm frozen bovine
      brain stem, cortex, and cerebellum tissue sections were washed with a series of
      solvent solutions to remove lipids before applying heparin lyases I, II, and III
      on the tissue surfaces within 5 mm * 5 mm digestion spots. The digested HS
      disaccharides were extracted from tissue surfaces and then analyzed by using size
      exclusion chromatography/mass spectrometry (SEC-MS). The results from bovine
      brain stem, cortex, and cerebellum demonstrated the reproducibility and
      reliability of our profiling method. We applied our method to detect HS from
      human astrocytoma (WHO grade II) and glioblastoma (GBM, WHO grade IV) frozen
      slides. Higher HS abundances and lower average sulfation level of HS were
      detected in glioblastoma (GBM, WHO grade IV) slides compared to astrocytoma (WHO
      grade II) slides. 

PMID- 24099044
TI  - Sirolimus encapsulated liposomes for cancer therapy: physicochemical and
      mechanical characterization of sirolimus distribution within liposome bilayers.
AB  - Sirolimus has recently been introduced as a therapeutic agent for breast and
      prostate cancer. In the current study, conventional and Stealth liposomes were
      used as carriers for the encapsulation of sirolimus. The physicochemical
      characteristics of the sirolimus liposome nanoparticles were investigated
      including the particle size, zeta potential, stability and membrane integrity. In
      addition atomic force microscopy was used to study the morphology, surface
      roughness and mechanical properties such as elastic modulus deformation and
      deformation. Sirolimus encapsulation in Stealth liposomes showed a high degree of
      deformation and lower packing density especially for dipalmitoyl
      phosphatidylcholine (DPPC) Stealth liposomes compared to unloaded. Similar
      results were obtained by differential scanning calorimetry (DSC) studies;
      sirolimus loaded liposomes were found to result in a distorted state of the
      bilayer. X-ray photon electron (XPS) analysis revealed a uniform distribution of
      sirolimus in multilamellar DPPC Stealth liposomes compared to a nonuniform,
      greater outer layer lamellar distribution in distearoylphosphatidylcholine (DSPC)
      Stealth liposomes. 

PMID- 24099045
TI  - Retention of knowledge and perceived relevance of basic sciences in an integrated
      case-based learning (CBL) curriculum.
AB  - BACKGROUND: Knowledge and understanding of basic biomedical sciences remain
      essential to medical practice, particularly when faced with the continual
      advancement of diagnostic and therapeutic modalities. Evidence suggests, however,
      that retention tends to atrophy across the span of an average medical course and
      into the early postgraduate years, as preoccupation with clinical medicine
      predominates. We postulated that perceived relevance demonstrated through
      applicability to clinical situations may assist in retention of basic science
      knowledge. METHODS: To test this hypothesis in our own medical student cohort, we
      administered a paper-based 50 MCQ assessment to a sample of students from Years 2
      through 5. Covariates pertaining to demographics, prior educational experience,
      and the perceived clinical relevance of each question were also collected.
      RESULTS: A total of 232 students (Years 2-5, response rate 50%) undertook the
      assessment task. This sample had comparable demographic and performance
      characteristics to the whole medical school cohort. In general, discipline
      specific and overall scores were better for students in the latter years of the
      course compared to those in Year 2; male students and domestic students tended to
      perform better than their respective counterparts in certain disciplines. In the
      clinical years, perceived clinical relevance was significantly and positively
      correlated with item performance. CONCLUSIONS: This study suggests that perceived
      clinical relevance is a contributing factor to the retention of basic science
      knowledge and behoves curriculum planners to make clinical relevance a more
      explicit component of applied science teaching throughout the medical course.

PMID- 24099046
TI  - Poly(N-vinyl-2-pyrrolidone-co-vinyl alcohol), a versatile amphiphilic polymeric
      scaffold for multivalent probes.
AB  - A convenient scaffold based on poly(N-vinyl-2-pyrrolidone-co-vinyl alcohol) is
      proposed for presenting ligands in multivalent format. This amphiphilic polymer
      supports synthesis of conjugates in both organic and aqueous media, permits
      enzymatic processing of the ligand precursor, and, finally, offers a choice of
      formats for evaluation of biological activity either as a soluble inhibitor or as
      a capture reagent after deposition on a hydrophobic surface or standard
      microtiter plates. 

PMID- 24099047
TI  - Low Serum retinol-binding protein-4 levels in acute exacerbations of chronic
      obstructive pulmonary disease at intensive care unit admission is a predictor of
      mortality in elderly patients.
AB  - BACKGROUND: Acute exacerbations of chronic obstructive pulmonary disease (AECOPD)
      are thought to be associated with increased mortality in elderly patients. Low
      retinol-binding protein-4 (RBP4) is associated with a high risk of respiratory
      infections in the general population. Therefore, we hypothesized that low RBP4
      levels are associated with an increased risk of AECOPD and can be used as a
      biomarker for AECOPD in elderly patients. METHODS: Enzyme-linked immunosorbent
      assays were used to assess RBP4 levels in elderly with AECOPD within the first 24
      hours after intensive care unit admission. Forty-six elderly patients with stable
      COPD in outpatient clinics and 50 healthy elderly persons who had physical
      examinations as outpatients were controls. RESULTS: In AECOPD patients, RBP4
      levels were lower than those in stable COPD patients and healthy controls (59.7
      vs 91.2 and 113.6 mg/L, p < 0.001). RBP4 levels were decreased by 30.6% in non
      survivors compared with survivors (51.5 vs 74.2 mg/L, p < 0.001). A higher Acute
      Physiology and Chronic Health Enquiry II (APACHE II) score and Simplified Acute
      Physiology score (SAPS II) were associated with lower RBP4 levels (r = -0.692, p
      = 0.024 and r = -0.670, p = 0.015, respectively). RBP4 was positively correlated
      with creatinine and body mass index, and negatively correlated with C-reactive
      protein and Global Initiative for Chronic Obstructive Lung Disease stage.
      Multivariate logistic regression showed that RBP4 was an independent mortality
      predictor of AECOPD (odds ratio: 0.926, p = 0.007). Analysis of the area under
      the receiver operating characteristic (AUC) curve showed that RBP4 showed good
      discrimination (AUC: 0.88; 95% confidence interval: 0.78-0.94; p = 0.008) in
      predicting mortality. RBP4 improved the prognostic accuracy of mortality for the
      APACHE II and SAPS II scores. CONCLUSIONS: Serum RBP4 levels are significantly
      reduced in elderly AECOPD patients. RBP4 might be a good predictive biomarker for
      mortality in elderly AECOPD patients in the intensive care unit.

PMID- 24099048
TI  - A retrospective survey on rotated drawing in persons with mild cognitive
      impairment or degenerative dementia.
AB  - Rotation of drawings has been described in focal brain lesions, at copy when the
      dorsal visual stream is involved, at recall in patients with memory or frontal
      dysfunction. In the present study Rey-Osterrieth Complex Figure performance was
      reviewed in 445 consecutive patients with mild cognitive impairment or
      degenerative dementia; a smaller sample (n = 243) had also performed the recall
      trial. Rotation was present in 19 cases overall: at copy in 11, at recall in 7,
      and at recall on a first assessment and at copy on retest in 1 last patient.
      Rotation at copy was often associated with neuropsychological and metabolic
      imaging evidence of parietal dysfunction, supporting previous evidence that
      rotation at copy might be due to an impairment of object perception processes
      within the dorsal visual stream. Rotation at recall seemed to be related
      predominantly to executive deficits, but no specific hypothesis on its cognitive
      origin can be advanced based on the present data. 

PMID- 24099049
TI  - Repositioning therapeutic cancer vaccines in the dawning era of potent immune
      interventions.
AB  - Based on lessons learned with various immune interventions, this review aims to
      provide a constructive framework for repositioning therapeutic cancer
      vaccination. Intensive research throughout the past decade has identified key
      hurdles interfering with the efficacy of cancer vaccines. The vaccination concept
      still holds promise if positioned appropriately in minimal residual disease and
      select early disease stage cancer indications. However, in advanced cancer, it
      must be integrated with complementary immune interventions to ensure
      reconstruction of a functional immune repertoire and simultaneous blockade of
      immune inhibiting mechanisms. Vaccination could render complex and integrative
      immune interventions simpler, safer and more effective. The near future will
      witness an explosion of activities in the cancer immunotherapy arena, witnessing
      a rational repositioning of vaccines rather than their extinction. 

PMID- 24099050
TI  - The contribution of Italian epileptologists to the advancement of the scientific
      knowledge in epilepsy is substantial. Introduction.

PMID- 24099051
TI  - Withdrawal of antiepileptic drugs: guidelines of the Italian League Against
      Epilepsy.
AB  - The Italian League Against Epilepsy has issued evidence-based guidelines to help
      practicing physicians in their decision to stop or withhold antiepileptic drugs
      (AEDs) in patients achieving a prolonged period of seizure freedom. Six adult and
      two child neurologists, divided into four pairs, critically appraised 128
      published reports and provided graded recommendations answering 15 key questions:
      length of the seizure-free period after treatment initiation, difference in
      seizure-free periods in children and adults, electroencephalography (EEG) pattern
      at the time of discontinuation, etiology of epilepsy, seizure type(s), patient's
      age and sex, family history of epilepsy, history of febrile seizures, epilepsy
      syndrome, seizure frequency before entering remission, duration of active
      epilepsy, tapering period, number and type of AEDs taken at time of
      discontinuation, combination of risk factors for recurrence, and length of
      patient monitoring after treatment discontinuation. Based on the available data,
      the following recommendations can be outlined: (1) antiepileptic treatment might
      be discontinued after a minimum period of 2 years of seizure freedom; shorter
      seizure-free periods are associated to a higher risk of relapse; (2) in children,
      AED discontinuation could be considered after less than two seizure-free years
      because of a marginally higher risk of relapse for early withdrawal; (3) factors,
      such as abnormal EEG (including epileptiform abnormalities) at the time of
      treatment discontinuation, a documented etiology of seizures (including mental
      retardation, perinatal insults, and abnormal neurologic examination), partial
      seizures, or an older age at disease onset, enhance the risk of relapse; however,
      patients should not be encouraged to withhold treatment unless a combination of
      two or more of these factors is present; (4) female sex, family history of
      epilepsy, history of febrile seizures, disease length/severity, and number and
      type of drugs taken should not influence the decision to stop treatment; (5)
      epilepsy syndrome should be always included in the decision process; (6) slow (at
      least 6 months) AED discontinuation should be encouraged; in any case the
      duration of the tapering period should be tailored to the patient's needs and
      preference; and (7) patient discontinuing treatment should be followed for no <2
      years. As a general habit, the decision to stop treatment should be discussed and
      shared with each patient, taking into account social and personal complications
      of a seizure relapse and the medical complications of chronic AED treatment.

PMID- 24099052
TI  - Epilepsy and vaccinations: Italian guidelines.
AB  - Reports of childhood epilepsies in temporal association with vaccination have had
      a great impact on the acceptance of vaccination programs by health care
      providers, but little is known about this possible temporal association and about
      the types of seizures following vaccinations. For these reasons the Italian
      League Against Epilepsy (LICE), in collaboration with other Italian scientific
      societies, has decided to generate Guidelines on Vaccinations and Epilepsy. The
      aim of Guidelines on Vaccinations and Epilepsy is to present recent unequivocal
      evidence from published reports on the possible relationship between vaccines and
      epilepsy in order to provide information about contraindications and risks of
      vaccinations in patients with epilepsy. The following main issues have been
      addressed: (1) whether contraindications to vaccinations exist in patients with
      febrile convulsions, epilepsy, and/or epileptic encephalopathies; and (2) whether
      any vaccinations can cause febrile seizures, epilepsy, and/or epileptic
      encephalopathies. Diphtheria-tetanus-pertussis (DTP) vaccination and measles,
      mumps, and rubella vaccination (MMR) increase significantly the risk of febrile
      seizures. Recent observations and data about the relationships between
      vaccination and epileptic encephalopathy show that some cases of apparent vaccine
      induced encephalopathy could in fact be caused by an inherent genetic defect with
      no causal relationship with vaccination. 

PMID- 24099053
TI  - Treatment of convulsive status epilepticus in childhood: recommendations of the
      Italian League Against Epilepsy.
AB  - The Italian League Against Epilepsy Commission Guidelines Subcommittee on Status
      Epilepticus (SE) has published an article on the management of SE in adults, and
      now presents a report on the management of convulsive status epilepticus (CSE) in
      children, excluding the neonatal period. Children's greater susceptibility than
      adults to epileptic seizures results from many factors. Earlier maturation of
      excitatory than inhibitory synapses, increased susceptibility and concentration
      of receptors for excitatory neurotransmitters, peculiar composition of the
      receptor subunits resulting in slower and less effective inhibitory responses,
      all cause the high incidence of SE in the pediatric population. The related
      morbidity and mortality rates, although lower than in adults, require immediate
      diagnosis and therapy. The division into focal and generalized, nonconvulsive and
      convulsive SE is applied in children and adolescents, as is the distinction in
      the three different stages according to the time elapsed since the start of the
      event and the response to drugs (initial, defined, and refractory SE). In
      children and adolescents, an "operational definition" is also accepted to allow
      earlier treatment (starting at 5-10 min). Maintenance and stabilization of vital
      functions, cessation of convulsions, diagnosis, and initial treatment of
      potentially "life-threatening" causes are the objectives to be pursued in the
      management of children with CSE. The need for early pharmacologic intervention
      stresses the need for action in the prehospital setting, generally using rectal
      diazepam. In hospital, parenteral benzodiazepines are used (lorazepam, diazepam,
      or midazolam). When first-line drugs fail, sodium phenytoin and phenobarbital
      should be used. As alternatives to phenobarbital, the following can be considered
      for treatment of refractory CSE: valproate, levetiracetam, and lacosamide. In
      cases with refractory CSE, pharmacologic options can be thiopental, midazolam, or
      propofol in continuous intravenous infusions to suppress electroencephalographic
      bursts and convulsive activity. These drugs need to be administered in intensive
      care units to ensure the monitoring and support of vital signs and brain
      electrical activity.

PMID- 24099054
TI  - Overview of presurgical assessment and surgical treatment of epilepsy from the
      Italian League Against Epilepsy.
AB  - The Commission for Epilepsy Surgery of the Italian League Against Epilepsy (LICE)
      presents an overview of the techniques and methodologies of presurgical
      evaluation and of the surgical treatment of epilepsies. This overview is the
      result of the experience developed in the past years in the major Italian centers
      where programs of epilepsy surgery have been established, and it has the aim of
      offering a quick and easy reference tool for those involved in the treatment of
      patients with epilepsy. The sharing of different experiences has the additional
      aim of conforming and disseminating the employed techniques as well as the
      methods of selection and evaluation of patients. The synthetic coverage of the
      main issues concerning the presurgical workup and the available surgical options
      will hopefully provide a framework that may integrate and develop the
      contributions of every single center, in one of the more complex, challenging,
      and dynamic areas of neurological sciences. 

PMID- 24099055
TI  - Health Technology Assessment report on the presurgical evaluation and surgical
      treatment of drug-resistant epilepsy.
AB  - PURPOSE: Epilepsy is a neurologic disorder with major social impact. Surgery is a
      valuable option in patients who are not responding to antiepileptic drugs. The
      literature reports demonstrate that a proportion ranging from 40 to 100% of
      patients with epilepsy achieve seizure remission after surgery. A presurgical
      evaluation (clinical and instrumental) must be performed in all patients with
      drug-resistant epilepsy to assess their suitability for surgical intervention.
      Health Technology Assessment (HTA) represents a modern approach to the analysis
      of technologies used for health care. HTA could be considered a bridge between
      science that produces evidence and the decisions that can be taken on the basis
      of that evidence at different levels of the health care system. The aim of this
      study is the HTA of epilepsy surgery including clinical, ethical, social, and
      economic features. METHODS: The present study includes an analysis of the
      diagnostic and surgical workup performed at the Italian centers for the diagnosis
      and treatment of drug-resistant epilepsy (DRE). The study includes the following
      issues: (1) social, ethical impact, and costs of the disease; (2) clinical
      results, efficacy, and safety of surgery; (3) ethics and quality of life after
      surgery; and (4) economic impact and productivity regained after surgery. The
      cost of managing a patient with DRE included in the presurgical study was
      estimated by the bottom-up microcosting technique that starts from a detailed
      collection of data on consumption of resources and full costing. The phases
      analyzed were (1) noninvasive diagnostic workup; (2) neurosurgical intervention;
      and (3) follow-up. KEY FINDINGS: The literature reports indicate epilepsy surgery
      as an effective treatment both on clinical results and on ethical, social, and
      quality of life aspects. The workup including the noninvasive presurgical study
      followed by surgery has a total cost of ?20,827. Management of short-term follow
      up increases the overhead to ?22,291 at the first year, and then to ?23,571 after
      5 years. According to the estimates made in this survey, funding based on
      diagnosis-related group (DRG) tariff for the noninvasive diagnostic stage
      involving hospital admission is not remunerative in Italy either at regional or
      national levels. Effectively the difference between full cost and DRG has a delta
      of ?3,402 and ?2,537 respectively. The total cost of the presurgical, surgical,
      and follow-up evaluation is not remunerative for ?10,554 (national data).
      SIGNIFICANCE: Economic surveys in Italy have shown that surgery for DRE is an
      advantageous treatment from the standpoint of third-party payers and is cost
      effective for society. DRE presurgical evaluation and surgery are not
      remunerative either at regional or national levels.

PMID- 24099056
TI  - The spectrum of epileptic syndromes with fixation off sensitivity persisting in
      adult life.
AB  - PURPOSE: The term "fixation off sensitivity" (FOS) was proposed by
      Panayiotopoulos to describe epilepsy/electroencephalography (EEG) changes evoked
      by the suppression of central vision and fixation. The EEG pattern usually
      consists of spike/polyspike and waves localized in occipital regions. FOS occurs
      mainly in children with idiopathic occipital partial epilepsies and rarely in
      adults. In this retrospective study we evaluated the clinical data, EEG, and
      magnetic resonance imaging (MRI) findings of patients with epilepsy and FOS
      persisting in adult life to better define the spectrum of syndromes. METHODS: We
      selected 15 consecutive patients (12 female/3 male; age range 19-59 years). The
      main inclusion criterion was the diagnosis of epilepsy with FOS persisting in
      adult life. We retrospectively analyzed clinical EEG and neuroimaging data. KEY
      FINDINGS: We observed a female prevalence (F/M = 12/3). Eight patients presented
      both simple and complex partial seizures, whereas seven had only complex partial
      seizures. Partial seizures evolved into generalized seizures/hemiconvulsions in
      nine cases. The FOS pattern consisted of spike-and-wave and slow-wave
      abnormalities with posterior localization (bilateral in eight/monolateral in
      seven). We recorded seizures in 10/15 patients. All showed a posterior onset
      (bilateral in 2/left in 2/right in 6). FOS was prevalent in symptomatic epilepsy
      (cortical malformations in 7; celiac disease in 3; calcified vascular
      malformation in 1). One patient presented cryptogenic epilepsy and only three
      idiopathic epilepsy (Gastaut syndrome). SIGNIFICANCE: FOS can be observed in
      adult life in idiopathic epilepsy, representing the "prolongation" of the same
      phenomenon arisen during childhood. Nevertheless, it often represents the EEG
      expression of symptomatic epilepsies (cortical malformations/celiac disease).

PMID- 24099057
TI  - Early onset absence epilepsy with onset in the first year of life: a multicenter
      cohort study.
AB  - PURPOSE: Absence epilepsy with onset before age 4 years, or early onset absence
      epilepsy (EOAE), has been rarely reported, and children with onset in the first
      year of life are considered almost exceptional. We aimed to report the clinical
      and electrophysiologic features of a cohort of children with absence epilepsy
      starting within the first year of life. METHODS: This was a multicenter study
      including patients with absence epilepsy starting within the first year of life
      and identified over a 20-year period (1991-2011). KEY FINDINGS: We identified 16
      patients with absence epilepsy starting within the first year of life with a mean
      follow-up of 6.4 years. Mean age at seizure onset was 10.3 +/- (standard
      deviation)1.4 months (range 8-12). Two patients experienced rare tonic-clonic
      seizures that started later than the absences. None of the subjects had episodes
      of absence status epilepticus. Eleven subjects were seizure-free with the first
      antiepileptic drug. In eight children, therapy was withdrawn after a mean 3.2
      years of treatment. None evolved into a different form of idiopathic generalized
      epilepsy. SLC2A1 gene analysis in 12 children (75%) failed to reveal glucose
      transporter 1 deficiency. SIGNIFICANCE: EOAE, including patients with onset
      within the first year of life, should be no more considered a distinct idiopathic
      generalized epilepsy (IGE) syndrome, as it shows electroclinical features,
      response to therapy, and prognosis similar to childhood absence epilepsy.
      Moreover, early age of onset is not predictive of GLUT-1 deficiency and genetic
      analysis may be therefore avoided in patients meeting strict inclusion criteria.

PMID- 24099058
TI  - Epilepsy surgery in children: evaluation of seizure outcome and predictive
      elements.
AB  - PURPOSE: To analyze the clinical outcome of epilepsy surgery in children, and to
      identify the factors related with a favorable seizure control among several
      presurgical, surgical and postsurgical variables. METHODS: One-hundred twenty
      children, younger than 16 years (69 male and 51 female), operated on for
      medically refractory focal epilepsy at the "C.Munari" Epilepsy Surgery Center of
      the Niguarda Hospital in Milan from 1998 to 2009, were identified. Seizure
      outcome was assessed according to the Engel's classification. Statistical
      analysis was performed to identify predictive elements of seizure outcome among
      several presurgical, surgical, and postsurgical variables. KEY FINDINGS: There
      were 84 (70%) seizure-free patients (Engel's classes Ia and Ic), 93 (77.5%) in
      class I, 8 (6.7%) in class II, 9 in class III (7.5%), and 10 (8.3%) in class IV.
      SIGNIFICANCE: Our study confirms that epilepsy surgery is an established and
      effective treatment for partial epilepsy in children and suggest criteria to help
      identify early potential surgical candidates.

PMID- 24099059
TI  - Long-term evolution of neuropsychological competences in encephalopathy with
      status epilepticus during sleep: a variable prognosis.
AB  - PURPOSE: The aim of this study was to evaluate the long-term cognitive outcome in
      children with continuous spikes and waves during slow wave sleep (CSWS syndrome).
      METHODS: We reviewed the neuropsychological tests of 25 children diagnosed with
      CSWS between 1987 and 2010 and with a mean follow-up of 13.5 years. KEY FINDINGS:
      Cognitive performances worsened during CSWS in virtually all patients. Seven
      patients (28%) with nonlesional epilepsy had a positive outcome; three patients
      (12%) showed persistence of motor deficit without involvement of cognitive
      functions; and seven patients (28%) who presented a long duration of CSWS (mean =
      28.1 months) had a negative cognitive outcome. In 6 patients (24%) with
      structural or metabolic disorders before CSWS onset cognitive outcomes did not
      change; 2 patients (8%) had a negative outcome irrespective of the duration or
      presence of other neurologic disorders before CSWS onset. Forty-four percent of
      children with CSWS demonstrated permanent cognitive impairment. SIGNIFICANCE: The
      long-term outcome of CSWS syndrome is variable and seems to depend on treatment
      response, disease duration, and underlying etiology.

PMID- 24099061
TI  - Standardisation of disk diffusion results for antibiotic susceptibility testing
      using the sirscan automated zone reader.
AB  - BACKGROUND: Standardisation of disk diffusion readings could improve
      reproducibility and accuracy of antibiotic susceptibility testing (AST). This
      study evaluated accuracy, reproducibility, and precision of automated inhibition
      zone reading using the "Sirscan automatic" zone reader (i2a, Perols Cedex,
      France). RESULTS: In a first step we compared Sirscan results with manual
      calliper measurements for comparability and accuracy. Sirscan readings were
      checked and adjusted on-screen as recommended by the manufacturer. One hundred
      clinical bacterial isolates representing a broad spectrum of organisms routinely
      isolated in a clinical laboratory were tested, and zone diameter values and
      interpretation according to EUCAST guidelines were compared. In a second step we
      analysed, whether fully automated zone reading can decrease standard deviation of
      diameter measurements and, thus, improve reproducibility and precision of the
      disk diffusion method. Standard deviations of manual measurements, on-screen
      adjusted Sirscan measurements, and fully automated Sirscan readings were compared
      for 19 repeat independent measurements of inhibition zones of S. aureus ATCC
      29213, E. coli ATCC 25922, and P. aeruginosa ATCC 27853 (EUCAST quality control
      strains).On-screen adjusted Sirscan and calliper measurements displayed high
      comparability. No significant differences were detected comparing the results of
      both reading methods. Standard deviations of inhibition zone diameters were
      significantly lower for fully automated Sirscan measurements compared with both
      adjusted Sirscan readings and the manual method, resulting in better
      reproducibility and precision of the automated readings. CONCLUSIONS: Our results
      indicate that fully automated zone reading can further improve standardisation of
      AST by decreasing standard deviation and, thus, improve precision of inhibition
      zone diameter results.

PMID- 24099062
TI  - Comment on "long-term reproducibility of Edinger-Westphal stimulated
      accommodation in rhesus monkeys" by He et al. (Exp. Eye Res. XXX (2013) XX-XX).

PMID- 24099063
TI  - Response to letter from Dr. Schachar.

PMID- 24099064
TI  - Increasing intraocular pressure as treatment for papilledema.

PMID- 24099065
TI  - Theoretical exploration of photoisomerization-switchable second-order nonlinear
      optical responses of two-dimendional lambda- and w-shaped polyoxometalate
      derivatives of dithienylperfluorocyclopentene.
AB  - The switchable second-order nonlinear optical (NLO) properties on two-dimensional
      (2D) molecules based on Lindqvist-type [Mo6O19](2-) and
      dithienylperfluorocyclopentene (DTE) have been investigated at density functional
      theory (DFT) level. The CAM-B3LYP and M06-2X functionals were employed to study
      the switching behavior on NLO properties by photoisomerization reaction. The
      betatot value of system 2c (closed-ring form) is 15920.5 au, which is 150.1 times
      larger than that of the corresponding open-ring form (system 2o). The time
      dependent DFT calculations predict that the charge transfer from DTE to
      polyoxometalate, and DTE intramolecular charge transfer in closed-ring systems
      effectively improve the static first hyperpolarizability. Furthermore, the Lambda
      shaped systems possess a larger u value than those of W-shaped systems owing to
      different orientation for substituent groups. 

PMID- 24099060
TI  - Epilepsy in primary cerebral tumors: the characteristics of epilepsy at the onset
      (results from the PERNO study--Project of Emilia Romagna Region on Neuro
      Oncology).
AB  - PURPOSE: To present new information on the semiology and short-term evolution of
      seizures associated with primary brain tumors (PBTs) in a prospective study.
      METHODS: This study is a section of the PERNO study--Project of Emilia Romagna
      Region on Neuro-Oncology, the main aim of which is to collect prospectively all
      cases of PBTs occurring in the Emilia-Romagna region, northeast Italy (3,983,346
      population) from January 2009 to December 2011, to allow epidemiologic, clinical,
      and biomolecular studies. The epilepsy section of the PERNO study included all
      the patients who experienced seizures, either as first symptom of the tumor or
      appearing during the course of the disease. Each patient was interviewed by the
      referring neurologist with a specific interest in epilepsy. The patients who
      entered the study were followed up with visits on a quarterly basis. KEY
      FINDINGS: We collected 100 cases with full clinical, neuroradiologic, and
      pathologic data. The majority (79%) had high grade PBTs (glioblastoma in 50
      cases), whereas the remaining patients had low-grade gliomas, mostly localized in
      the frontal (60%), temporal (38%), and parietal (28%) lobes. Seizures were the
      first symptom of the tumor in 72 cases. Overall, the initial seizures were tonic
      clonic (48%) (without clear initial focal signs in more than half of the
      patients), focal motor (26%), complex partial (10%), and somatosensitive (8%).
      The majority of cases (60%) had isolated seizures or a low seizure frequency at
      the onset of the disease, whereas a high seizure frequency or status epilepticus
      was observed in 18% and 12% of cases, respectively. Ninety-two patients underwent
      surgical removal of the tumor, which was either radical (38%) or partial (53%).
      Seven patients underwent only cerebral biopsy. In the 72 patients in whom
      seizures were the first symptom, the mean time to the surgical treatment was 174
      days, with a significant difference between high grade (95 days) and low grade
      (481 days) gliomas. At the time of our first observation, the majority of
      patients (69%) had already undergone surgical removal, with a mean follow-up of 3
      months after the procedure. Overall, 39 patients (56%) were seizure free after
      tumor removal. The good outcome did not depend on presurgical seizure frequency
      or tumor type, although there was a trend for better results with low-grade PBTs.
      SIGNIFICANCE: These data provide evidence that seizures are strictly linked to
      the tumoral lesion: They are the initial symptom of the tumor, reflect the tumor
      location and type, are usually resistant to antiepileptic treatment, and may
      disappear after the treatment of the lesion.

PMID- 24099066
TI  - Precise colocalization of interacting structural and pigmentary elements
      generates extensive color pattern variation in Phelsuma lizards.
AB  - BACKGROUND: Color traits in animals play crucial roles in thermoregulation,
      photoprotection, camouflage, and visual communication, and are amenable to
      objective quantification and modeling. However, the extensive variation in non
      melanic pigments and structural colors in squamate reptiles has been largely
      disregarded. Here, we used an integrated approach to investigate the
      morphological basis and physical mechanisms generating variation in color traits
      in tropical day geckos of the genus Phelsuma. RESULTS: Combining histology,
      optics, mass spectrometry, and UV and Raman spectroscopy, we found that the
      extensive variation in color patterns within and among Phelsuma species is
      generated by complex interactions between, on the one hand, chromatophores
      containing yellow/red pteridine pigments and, on the other hand, iridophores
      producing structural color by constructive interference of light with guanine
      nanocrystals. More specifically, we show that 1) the hue of the vivid
      dorsolateral skin is modulated both by variation in geometry of structural,
      highly ordered narrowband reflectors, and by the presence of yellow pigments, and
      2) that the reflectivity of the white belly and of dorsolateral pigmentary red
      marks, is increased by underlying structural disorganized broadband reflectors.
      Most importantly, these interactions require precise colocalization of yellow and
      red chromatophores with different types of iridophores, characterized by ordered
      and disordered nanocrystals, respectively. We validated these results through
      numerical simulations combining pigmentary components with a multilayer
      interferential optical model. Finally, we show that melanophores form dark
      lateral patterns but do not significantly contribute to variation in blue/green
      or red coloration, and that changes in the pH or redox state of pigments provide
      yet another source of color variation in squamates. CONCLUSIONS: Precisely
      colocalized interacting pigmentary and structural elements generate extensive
      variation in lizard color patterns. Our results indicate the need to identify the
      developmental mechanisms responsible for the control of the size, shape, and
      orientation of nanocrystals, and the superposition of specific chromatophore
      types. This study opens up new perspectives on Phelsuma lizards as models in
      evolutionary developmental biology.

PMID- 24099067
TI  - Seamless vascularized large-diameter tubular collagen scaffolds reinforced with
      polymer knittings for esophageal regenerative medicine.
AB  - A clinical demand exists for alternatives to repair the esophagus in case of
      congenital defects, cancer, or trauma. A seamless biocompatible off-the-shelf
      large-diameter tubular scaffold, which is accessible for vascularization, could
      set the stage for regenerative medicine of the esophagus. The use of seamless
      scaffolds eliminates the error-prone tubularization step, which is necessary when
      emanating from flat scaffolds. In this study, we developed and characterized
      three different types of seamless tubular scaffolds, and evaluated in vivo tissue
      compatibility, including vascularization by omental wrapping. Scaffolds (luminal
      O ~ 1.5 cm) were constructed using freezing, lyophilizing, and cross-linking
      techniques and included (1) single-layered porous collagen scaffold, (2) dual
      layered (porous+dense) collagen scaffold, and (3) hybrid scaffold
      (collagen+incorporated polycaprolacton knitting). The latter had an ultimate
      tensile strength comparable to a porcine esophagus. To induce rapid
      vascularization, scaffolds were implanted in the omentum of sheep using a
      wrapping technique. After 6 weeks of biocompatibility, vascularization,
      calcification, and hypoxia were evaluated using immunohistochemistry. Scaffolds
      were biocompatible, and cellular influx and ingrowth of blood vessels were
      observed throughout the whole scaffold. No calcification was observed, and slight
      hypoxic conditions were detected only in the direct vicinity of the polymer
      knitting. It is concluded that seamless large-diameter tubular collagen-based
      scaffolds can be constructed and vascularized in vivo. Such scaffolds provide
      novel tools for esophageal reconstruction.

PMID- 24099068
TI  - Isotretinoin updates.
AB  - Acne vulgaris is a chronic inflammatory disease of pilosebaceous follicles
      commonly affecting adolescents and young adults. This disease has a profound
      psychological impact on affected individuals and treatment has been shown to
      significantly improve both self-esteem and quality of life. Isotretinoin is an
      effective medication used primarily in severe cystic acne patients. Over the past
      30 years, this medication has revolutionized the treatment of acne. However,
      despite its popularity there are numerous side effects associated with its use.
      Most of its side effects are predictable and dose dependent, which has led to the
      development of variable dose regimens. Unfortunately, rare but significant side
      effects (e.g., depression, inflammatory bowel disease) do occur and necessitate
      careful monitoring to improve clinical outcomes and minimize potential adverse
      events. 

PMID- 24099069
TI  - Acitretin.
AB  - Acitretin, a synthetic retinoid, is the pharmacologically active metabolite of
      etretinate. It is currently approved by the US Food and Drug Administration for
      the treatment of severe psoriasis in adults and has been established as a second
      line therapy for the treatment of psoriasis resistant to the use of topical
      therapy. It is also an option for generalized pustular psoriasis, palmoplantar
      pustulosis, exfoliative erythrodermic psoriasis, and severe psoriasis in the
      setting of acitretin. It also has been shown to have chemo-preventative
      characteristics. Acitretin is limited by its teratogenicity and therefore
      considered inappropriate in most female patients of childbearing age. Common side
      effects include mucocutaneous dryness and elevated triglycerides. 

PMID- 24099070
TI  - Topical and oral bexarotene.
AB  - Bexarotene is a retinoid that specifically binds retinoid X receptors and has
      numerous effects on cellular growth and differentiation. It is approved for the
      treatment of cutaneous T cell lymphoma both topically and systemically. Adverse
      effects include hyperlipidemia, central hypothyroidism, and neutropenia with
      bexarotene capsules, and an irritant dermatitis with bexarotene gel. With
      aggressive management of these potential side effects, bexarotene is an
      additional option in the armamentarium for management of cutaneous T cell
      lymphoma. 

PMID- 24099071
TI  - Oral retinoids and plasma lipids.
AB  - Retinoids and rexinoids are prescribed for conditions ranging from acne vulgaris
      to hyperkeratosis to cutaneous T cell lymphoma. Dyslipidemia is a frequent
      consequence of the use of these drugs, with more than one-third of patients
      manifesting aberrations in triglyceride (TG) levels. The efficacy of retinoic
      acid derivatives is linked to their influence on lipid metabolism in the skin,
      which can impair systemic lipid trafficking and metabolism in some patients.
      Thus, baseline screening for preexisting dyslipidemia and regular follow-up lipid
      panels are mandated, especially when powerful agents such as bexarotene are used.
      Dietary modification, increased physical activity, and weight management are the
      cornerstones of initial management for mild hypertriglyceridemia, which is a
      contributor to cardiovascular risk. More severe impairments (fasting TG > 500
      mg/dL) warrant pharmacologic interventions early on to reduce the risk of
      pancreatitis. Retinoic acid derivative action, lipid metabolism, and treatment of
      incident dyslipidemias are reviewed to empower prescribers in management of
      adverse lipid effects. 

PMID- 24099072
TI  - Giant condyloma acuminata of Buschke-Lowenstein: successful treatment mainly by
      an innovative surgical method.
AB  - Many remedies can be applied to condyloma acuminatum. However, it is the most
      difficult to treat giant condyloma acuminatum because of bleeding, recurrence,
      intolerance of patients, etc. After careful physical examination, the present
      authors found the giant tumor was composed of many smaller cauliflower-like warts
      with long and thin pedicles. So the present authors successfully excised the
      giant tumor mainly by clamping and cutting the pedicles with the best effects,
      the least damage to the perineal and perianal areas and lower recurrence. After 2
      months, the patient recovered very well and remained free of recurrence at a 2
      year follow-up. 

PMID- 24099073
TI  - Rituximab for the treatment of lupus erythematosus panniculitis.
AB  - Lupus erythematosus panniculitis (LEP) or lupus profundus (LP) is a clinical
      variant of lupus eryhematosus that involves the deep dermis and the subcutaneous
      fat and is associated with tender subcutaneous nodules or plaques, with
      occasional ulceration, atrophy, and scarring. The management of this entity can
      be difficult because of the lack of response to conventional treatments, such as
      systemic steroids and antimalarials. The two patients of this study presented LP
      refractory to several therapies that demonstrated a remarkable improve to the
      infusion of the anti-CD20 monoclonal antibody, rituximab at a dosage of 375
      mg/m2/week. After the first infusion, painful lesions had resolved without the
      appearance of new lesions. Rituximab may be an effective treatment for patients
      with LP when other therapies are ineffective. To date, there is only one case
      report of LEP treated with rituximab in the literature.

PMID- 24099074
TI  - Isolated corymbose collagenoma responding to intralesional triamcinolone
      acetonide and hyaluronidase injections.
AB  - Collagenomas are connective tissue nevi with circumscribed hamartomatous
      proliferation of collagen. Due to their benign nature and lack of any simple
      medical treatment, they are most often left untreated. We present a case of
      isolated corymbose collagenoma, a distinct morphological variant not described
      hitherto that was successfully treated with intralesional injections of
      combination of triamcinolone acetonide and hyaluronidase. 

PMID- 24099075
TI  - Radiation recall dermatitis in course of epidemic Kaposi's sarcoma.
AB  - Radiation recall dermatitis is an acute, rare skin reaction confined to
      previously irradiated areas that can be triggered by chemotherapeutic drugs
      (generally doxorubicin and taxanes), which are administrated after radiotherapy.
      We describe this case report to discuss the timing of the different choice of
      treatments of progressive Kaposis's sarcoma (KS) disease. KS, the neoplastic
      disease associated with HHV-8 infection, is still the most commonly diagnosed
      malignancy in HIV-1 patients, even if its incidence dramatically declined in the
      highly active antiretroviral therapy (HAART) era. The cutaneous form of disease
      generally improves with HAART alone or in association with local treatment
      (cryotherapy, radiotherapy, intralesion chemotherapy), whereas disseminated
      and/or progressive disease needs to be treated with systemic chemotherapy. In
      selected patients with progressive disease, systemic and local therapeutic
      options should be associated. We report a case of a 30-year-old HIV-1-positive
      man, affected by epidemic cutaneous and mucosal KS, who received several cycles
      of chemotherapy in succession with radiotherapy and other chemotherapy treatments
      for disease progression. After 7 months, the end of the last rechallenge with
      chemotherapy, the patient presented cutaneous painful and ulcerated lesions on
      the same skin areas previously irradiated. 

PMID- 24099076
TI  - Nail bed defect covered with labial mucosa graft after subungal glomus tumor
      removal.
AB  - The nail bed is an important part of the nail unit. It supports the nail plate,
      but does not regenerate itself. The labial mucosa and the nail bed both lack a
      granular layer. Because the keratinization of the nail bed can cause poor nail
      adhesion, harvesting graft from nonkeratinized sites is preferred. Furthermore,
      harvesting graft from labial mucosa is convenient in surgical approach.
      Therefore, the labial mucosa is more eligible for covering the nail bed defect
      than other graft methods. In this report, a 46-year-old female patient suffered
      from a subungal glomus tumor of the right fourth fingernail bed for 10 years.
      After the nail plate was removed, complete excision of the tumor was performed,
      and a labial mucosa graft was used to cover the defect. Eight months after the
      operation, the tumor had not reoccurred and no nail deformity was observed. This
      outcome demonstrates that our procedure is a good surgical option for treatment
      of nail bed defects. 

PMID- 24099078
TI  - FKBP5 and CRHR1 polymorphisms moderate the stress-physical health association in
      a national sample.
AB  - OBJECTIVE: Stressful life events experienced during childhood and as an adult
      negatively impact mental and physical health over the life span. This study
      examined polymorphisms from 2 hypothalamic-pituitary-adrenal axis-related genes
      previously associated with posttraumatic stress disorder-FKBP5 and CRHR1-as
      moderators of the impact of child abuse and adult stress on physical health.
      METHOD: A national, community-based subsample of non-Hispanic European American
      respondents (n = 527) from a prospective longitudinal 3-year study of stress and
      coping (N = 2,729) provided saliva for genotyping. RESULTS: FKBP5 (rs1360780) and
      CRHR1 (rs12944712) polymorphisms significantly interacted with child abuse and
      adult stress to predict increases in physical health ailments over 3 years. Child
      abuse and adult stress were strongly related to physician-diagnosed physical
      ailments among individuals with the risk alleles of both single nucleotide
      polymorphisms. Individuals carrying the low-risk homozygotic genotypes were
      protected from the long-term negative health implications of experiencing both
      child abuse and adult stress. CONCLUSION: Consistent with theories linking the
      hypothalamic-pituitary-adrenal axis with stress-related disease, hypothalamic
      pituitary-adrenal axis polymorphism genotypes moderated the association between
      exposure to child abuse/adult stress and long-term physical health outcomes in a
      national sample.

PMID- 24099079
TI  - Pinoresinol inhibits proliferation and induces differentiation on human HL60
      leukemia cells.
AB  - Pinoresinol (PIN), one of the simplest lignans, is the precursor of other dietary
      lignans that are present in whole-grain cereals, legumes, fruits, and other
      vegetables. Several experimental and epidemiological evidences suggest that
      lignans may prevent human cancer in different organs. In this study we
      investigated the chemopreventive properties of PIN on cell lines derived from
      different sites either expressing or not the functional tumor suppressor protein
      p53. It was found that PIN inhibited the proliferation of p53 wild type colon and
      prostate tumor cells (HCT116 and LNCaP) while in breast cells the inhibition of
      growth was observed only in p53 mutant cells (MDA-MB-231). A potent
      antiproliferative activity of PIN was also observed on p53 null cells HL60 (IC50%
      8 MUM), their multidrug resistant variant HL60R (IC50% 32 MUM) and K562. On HL60
      cells, PIN caused a block of cell cycle in the G0/G1 phase, induced a weak
      proapoptotic effect but it was a good trigger of differentiation (NBT reduction
      and CD11b expression). PIN caused an upregulation of the CDK inhibitor
      p21(WAF1/Cip1) both at mRNA and protein levels so suggesting that this could be a
      mechanism by which PIN reduced proliferation and induced differentiation on HL60
      cells.

PMID- 24099077
TI  - Recommendations for human epidermal growth factor receptor 2 testing in breast
      cancer: American Society of Clinical Oncology/College of American Pathologists
      clinical practice guideline update.
AB  - PURPOSE: To update the American Society of Clinical Oncology (ASCO)/College of
      American Pathologists (CAP) guideline recommendations for human epidermal growth
      factor receptor 2 (HER2) testing in breast cancer to improve the accuracy of HER2
      testing and its utility as a predictive marker in invasive breast cancer.
      METHODS: ASCO/CAP convened an Update Committee that included coauthors of the
      2007 guideline to conduct a systematic literature review and update
      recommendations for optimal HER2 testing. RESULTS: The Update Committee
      identified criteria and areas requiring clarification to improve the accuracy of
      HER2 testing by immunohistochemistry (IHC) or in situ hybridization (ISH). The
      guideline was reviewed and approved by both organizations. RECOMMENDATIONS: The
      Update Committee recommends that HER2 status (HER2 negative or positive) be
      determined in all patients with invasive (early stage or recurrence) breast
      cancer on the basis of one or more HER2 test results (negative, equivocal, or
      positive). Testing criteria define HER2-positive status when (on observing within
      an area of tumor that amounts to >10% of contiguous and homogeneous tumor cells)
      there is evidence of protein overexpression (IHC) or gene amplification (HER2
      copy number or HER2/CEP17 ratio by ISH based on counting at least 20 cells within
      the area). If results are equivocal (revised criteria), reflex testing should be
      performed using an alternative assay (IHC or ISH). Repeat testing should be
      considered if results seem discordant with other histopathologic findings.
      Laboratories should demonstrate high concordance with a validated HER2 test on a
      sufficiently large and representative set of specimens. Testing must be performed
      in a laboratory accredited by CAP or another accrediting entity. The Update
      Committee urges providers and health systems to cooperate to ensure the highest
      quality testing.

PMID- 24099080
TI  - On the histone lysine methyltransferase activity of fungal metabolite chaetocin.
AB  - Histone lysine methyltransferases (HKMTs) are an important class of targets for
      epigenetic therapy. 1 (chaetocin), an epidithiodiketopiperazine (ETP) natural
      product, has been reported to be a specific inhibitor of the SU(VAR)3-9 class of
      HKMTs. We have studied the inhibition of the HKMT G9a by 1 and functionally
      related analogues. Our results reveal that only the structurally unique ETP core
      is required for inhibition, and such inhibition is time-dependent and
      irreversible (in the absence of DTT), ultimately resulting in protein
      denaturation. Mass spectrometric data provide a molecular basis for this effect,
      demonstrating covalent adduct formation between 1 and the protein. This provides
      a potential rationale for the selectivity observed in the inhibition of a variety
      of HKMTs by 1 in vitro and has implications for the activity of ETPs against
      these important epigenetic targets. 

PMID- 24099081
TI  - Drug-related harm among people who inject drugs in Thailand: summary findings
      from the Mitsampan Community Research Project.
AB  - BACKGROUND: For decades, Thailand has experienced high rates of illicit drug use
      and related harms. In response, the Thai government has relied on drug law
      enforcement to address this problem. Despite these efforts, high rates of drug
      use persist, and Thailand has been contending with an enduring epidemic of human
      immunodeficiency virus (HIV) among people who inject drugs (IDU). METHODS: In
      response to concerns regarding drug-related harm in Thailand and a lack of
      research focused on the experiences and needs of Thai IDU, the Mitsampan
      Community Research Project was launched in 2008. The project involved
      administering surveys capturing a range of behavioral and other data to community
      recruited IDU in Bangkok in 2008 and 2009. RESULTS: In total, 468 IDU in Bangkok
      were enrolled in the project. Results revealed high rates of midazolam injection,
      non-fatal overdose and incarceration. Syringe sharing remained widespread among
      this population, driven primarily by problems with access to syringes and
      methamphetamine injection. As well, reports of police abuse were common and found
      to be associated with high-risk behavior. Problems with access to evidence-based
      drug treatment and HIV prevention programs were also documented. Although
      compulsory drug detention centers are widely used in Thailand, data suggested
      that these centers have little impact on drug use behaviors among IDU in Bangkok.
      CONCLUSIONS: The findings from this project highlight many ongoing health and
      social problems related to illicit drug use and drug policies in Bangkok. They
      also suggest that the emphasis on criminal justice approaches has resulted in
      human rights violations at the hands of police, and harms associated with
      compulsory drug detention and incarceration. Collectively, the findings indicate
      the urgent need for the implementation of evidence-based policies and programs in
      this setting.

PMID- 24099082
TI  - pKa shifting in double-stranded RNA is highly dependent upon nearest neighbors
      and bulge positioning.
AB  - Shifting of pKa's in RNA is important for many biological processes; however, the
      driving forces responsible for shifting are not well understood. Herein, we
      determine how structural environments surrounding protonated bases affect pKa
      shifting in double-stranded RNA (dsRNA). Using (31)P NMR, we determined the pKa
      of the adenine in an A(+).C base pair in various sequence and structural
      environments. We found a significant dependence of pKa on the base pairing
      strength of nearest neighbors and the location of a nearby bulge. Increasing
      nearest neighbor base pairing strength shifted the pKa of the adenine in an
      A(+).C base pair higher by an additional 1.6 pKa units, from 6.5 to 8.1, which is
      well above neutrality. The addition of a bulge two base pairs away from a
      protonated A(+).C base pair shifted the pKa by only ~0.5 units less than a
      perfectly base paired hairpin; however, positioning the bulge just one base pair
      away from the A(+).C base pair prohibited formation of the protonated base pair
      as well as several flanking base pairs. Comparison of data collected at 25 
      degrees C and 100 mM KCl to biological temperature and Mg(2+) concentration
      revealed only slight pKa changes, suggesting that similar sequence contexts in
      biological systems have the potential to be protonated at biological pH. We
      present a general model to aid in the determination of the roles protonated bases
      may play in various dsRNA-mediated processes including ADAR editing, miRNA
      processing, programmed ribosomal frameshifting, and general acid-base catalysis
      in ribozymes.

PMID- 24099083
TI  - Mechanobiology and developmental control.
AB  - Morphogenesis is the remarkable process by which cells self-assemble into complex
      tissues and organs that exhibit specialized form and function during
      embryological development. Many of the genes and chemical cues that mediate
      tissue and organ formation have been identified; however, these signals alone are
      not sufficient to explain how tissues and organs are constructed that exhibit
      their unique material properties and three-dimensional forms. Here, we review
      work that has revealed the central role that physical forces and extracellular
      matrix mechanics play in the control of cell fate switching, pattern formation,
      and tissue development in the embryo and how these same mechanical signals
      contribute to tissue homeostasis and developmental control throughout adult life.

PMID- 24099084
TI  - Spermatogonial stem cell self-renewal and development.
AB  - Spermatogenesis originates from spermatogonial stem cells (SSCs). Development of
      the spermatogonial transplantation technique in 1994 provided the first
      functional assay to characterize SSCs. In 2000, glial cell line-derived
      neurotrophic factor was identified as a SSC self-renewal factor. This discovery
      not only provided a clue to understand SSC self-renewing mechanisms but also made
      it possible to derive germline stem (GS) cell cultures in 2003. In vitro culture
      of GS cells demonstrated their potential pluripotency and their utility in
      germline modification. However, in vivo SSC analyses have challenged the
      traditional concept of SSC self-renewal and have revealed their relationship with
      the microenvironment. An improved understanding of SSC self-renewal through
      functional assays promises to uncover fundamental principles of stem cell biology
      and will enable us to use these cells for applications in animal transgenesis and
      medicine. 

PMID- 24099085
TI  - TRP channels and pain.
AB  - Nociception is the process whereby primary afferent nerve fibers of the
      somatosensory system detect noxious stimuli. Pungent irritants from pepper, mint,
      and mustard plants have served as powerful pharmacological tools for identifying
      molecules and mechanisms underlying this initial step of pain sensation. These
      natural products have revealed three members of the transient receptor potential
      (TRP) ion channel family--TRPV1, TRPM8, and TRPA1--as molecular detectors of
      thermal and chemical stimuli that activate sensory neurons to produce acute or
      persistent pain. Analysis of TRP channel function and expression has validated
      the existence of nociceptors as a specialized group of somatosensory neurons
      devoted to the detection of noxious stimuli. These studies are also providing
      insight into the coding logic of nociception and how specification of nociceptor
      subtypes underlies behavioral discrimination of noxious thermal, chemical, and
      mechanical stimuli. Biophysical and pharmacological characterization of these
      channels has provided the intellectual and technical foundation for developing
      new classes of analgesic drugs.

PMID- 24099086
TI  - Synaptic laminae in the visual system: molecular mechanisms forming layers of
      perception.
AB  - Synaptic connections between neurons form the basis for perception and behavior.
      Synapses are often clustered in space, forming stereotyped layers. In the retina
      and optic tectum, multiple such synaptic laminae are stacked on top of each
      other, giving rise to stratified neuropil regions in which each layer combines
      synapses responsive to a particular sensory feature. Recently, several cellular
      and molecular mechanisms that underlie the development of multilaminar arrays of
      synapses have been discovered. These mechanisms include neurite guidance and cell
      cell recognition. Molecules of the Slit, Semaphorin, Netrin, and Hedgehog
      families, binding to their matching receptors, bring axons and dendrites into
      spatial register. These guidance cues may diffuse over short distances or bind to
      sheets of extracellular matrix, thus conditioning the local extracellular milieu,
      or are presented on the surface of cells bordering the future neuropil. In
      addition, mutual recognition of axons and dendrites through adhesion molecules
      with immunoglobulin domains ensures cell type-specific connections within a given
      layer. Thus, an elaborate genetic program assembles the parallel processing
      channels that underlie visual perception. 

PMID- 24099088
TI  - Cell and developmental biology of arbuscular mycorrhiza symbiosis.
AB  - The default mineral nutrient acquisition strategy of land plants is the symbiosis
      with arbuscular mycorrhiza (AM) fungi. Research into the cell and developmental
      biology of AM revealed fascinating insights into the plasticity of plant cell
      development and of interorganismic communication. It is driven by the prospect of
      increased exploitation of AM benefits for sustainable agriculture. The plant cell
      developmental program for intracellular accommodation of AM fungi is activated by
      a genetically defined signaling pathway involving calcium spiking in the nucleus
      as second messenger. Calcium spiking is triggered by chitooligosaccharides
      released by AM fungi that are probably perceived via LysM domain receptor
      kinases. Fungal infection and calcium spiking are spatiotemporally coordinated,
      and only cells committed to accommodating the fungus undergo high-frequency
      spiking. Delivery of mineral nutrients by AM fungi occurs at tree-shaped hyphal
      structures, the arbuscules, in plant cortical cells. Nutrients are taken up at a
      plant-derived periarbuscular membrane, which surrounds fungal hyphae and carries
      a specific transporter composition that is of direct importance for symbiotic
      efficiency. An elegant study has unveiled a new and unexpected mechanism for
      specific protein localization to the periarbuscular membrane, which relies on the
      timing of gene expression to synchronize protein biosynthesis with a redirection
      of secretion. The control of AM development by phytohormones is currently subject
      to active investigation and has led to the rediscovery of strigolactones. Nearly
      all tested phytohormones regulate AM development, and major insights into the
      mechanisms of this regulation are expected in the near future. 

PMID- 24099087
TI  - Viral membrane scission.
AB  - Virus budding is a complex, multistep process in which viral proteins make
      specific alterations in membrane curvature. Many different viral proteins can
      deform the membrane and form a budding virion, but very few can mediate membrane
      scission to complete the budding process. As a result, enveloped viruses have
      developed numerous ways of facilitating membrane scission, including hijacking
      host cellular scission machinery and expressing their own scission proteins.
      These proteins mediate scission in very different ways, though the biophysical
      mechanics underlying their actions may be similar. In this review, we explore the
      mechanisms of membrane scission and the ways in which enveloped viruses use these
      systems to mediate the release of budding virions. 

PMID- 24099090
TI  - Mentoring future Kenyan oncology researchers.
AB  - This is a summary of the 1st Academic Model Providing Access to Healthcare
      (AMPATH) Oncology Institute research grant writing workshop organized in
      collaboration with the Kenya Medical Research Institute (KEMRI) and held in
      Kisumu, Kenya from January 16th to 18th, 2013. The goal of this meeting was to
      mentor future Kenyan scientists and prioritize research topics that would lead to
      improved cancer care and survival for the citizens of Kenya. 

PMID- 24099089
TI  - In vivo imaging of bone using a deep-red fluorescent molecular probe bearing
      multiple iminodiacetate groups.
AB  - Deep-red fluorescent molecular probes are described that have a dendritic
      molecular architecture with a squaraine rotaxane core scaffold and multiple
      peripheral iminodiacetate groups as the bone targeting units. Iminodiacetates
      have an inherently lower bone affinity than bisphosphonates, and a major goal of
      the study was to determine how many appended iminodiacetate groups are required
      for effective deep-red fluorescence imaging of bone in living rodents. A series
      of in vitro and in vivo imaging studies showed that a tetra(iminodiacetate) probe
      stains bones much more strongly than an analogous bis(iminodiacetate) probe. In
      addition, a control tetra(iminodipropionate) probe exhibited no bone targeting
      ability. The tetra(iminodiacetate) probe targeted the same regions of high bone
      turnover as the near-infrared bisphosphonate probe OsteoSense750. Longitudinal
      studies showed that the fluorescence image signal from living mice treated with
      the tetra(iminodiacetate) probe was much more stable over 19 days than the signal
      from OsteoSense750. The narrow emission band of the tetra(iminodiacetate) probe
      makes it very attractive for inclusion in multiplex imaging protocols that employ
      a mixture of multiple fluorescent probes in preclinical studies of bone growth or
      in fluorescence guided surgery. The results also suggest that molecules or
      nanoparticles bearing multivalent iminodiacetate groups have promise as bone
      targeting agents with tunable properties for various pharmaceutical applications.

PMID- 24099091
TI  - An update on recent patents on thrombin inhibitors (2010 - 2013).
AB  - INTRODUCTION: Thromboembolic incidences have increased nearly 33% in the past
      decade and directly affect nearly 0.5% of the population. Heparin, warfarin and
      current direct thrombin inhibitors (DTIs), the primary anticoagulants of choice,
      suffer from several drawbacks. Thus, the search for an antithrombotic devoid of
      adverse effect continues in earnest. AREAS COVERED: Literature search covering
      PubMed, SciFinder(TM) Scholar, Web of Knowledge, Espacenet, PatentScope and
      Google Patent Search was used to uncover > 35 patents describing new chemical
      entities and advances in DTI technologies. Our search uncovered considerable
      emphasis on the development of larger more complex molecules such as peptide
      based inhibitors, prodrug derivatives, bivalent tryptophan zippers, triple action
      inhibitors and allosteric inhibitors. Advances in formulation technologies for
      clinically relevant DTIs have also been made. EXPERT OPINION: Thrombin is a
      multifaceted, dynamic enzyme with both coagulant and anticoagulant functions.
      Newer DTIs are attempting to fine tune thrombin's activity by targeting
      allosteric sites or by site-specific targeting of clotting. The complexity of
      thrombin's functions is driving the design of complex anticoagulants.
      Advancements in formulations and production processes have attempted to make
      traditional DTIs more cost effective to produce. The literature reveals a trend
      to develop a thrombin 'modulator' rather than an 'inhibitor.'

PMID- 24099092
TI  - Orthotopic heart transplantation in two infants with histiocytoid cardiomyopathy
      and left ventricular non-compaction.
AB  - HC is a rare cause of congestive heart failure that typically presents with
      malignant ventricular arrhythmias in infants, often requiring urgent
      intervention. Successful heart transplantation in a patient with HC has only been
      reported once (J Heart Lung Transplant 2004: 23: 902). The combination of HC with
      concurrent LVNC has only been described three times (Int J Legal Med 2009: 123:
      47; Hum Pathol 2005: 36: 403; Pediatr Dev Pathol 2012: 15: 397). We report two
      rare cases of HC with LVNC in two infants presenting with cardiogenic shock, one
      requiring ECMO support who was successfully bridged to orthotopic heart
      transplantation with a Berlin Heart LVAD. 

PMID- 24099094
TI  - The discrimination of interaural level difference sensitivity functions:
      development of a taxonomic data template for modelling.
AB  - BACKGROUND: A major cue for the position of a high-frequency sound source in
      azimuth is the difference in sound pressure levels in the two ears, Interaural
      Level Differences (ILDs), as a sound is presented from different positions around
      the head. This study aims to use data classification techniques to build a
      descriptive model of electro-physiologically determined neuronal sensitivity
      functions for ILDs. The ILDs were recorded from neurons in the central nucleus of
      the Inferior Colliculus (ICc), an obligatory midbrain auditory relay nucleus. The
      majority of ICc neurons (~ 85%) show sensitivity to ILDs but with a variety of
      different forms that are often difficult to unambiguously separate into different
      information-bearing types. Thus, this division is often based on laboratory
      specific and relatively subjective criteria. Given the subjectivity and non
      uniformity of ILD classification methods in use, we examined if objective data
      classification techniques for this purpose. Our key objectives were to determine
      if we could find an analytical method (A) to validate the presence of four
      typical ILD sensitivity functions as is commonly assumed in the field, and (B)
      whether this method produced classifications that mapped on to the
      physiologically observed results. METHODS: The three-step data classification
      procedure forms the basic methodology of this manuscript. In this three-step
      procedure, several data normalization techniques were first tested to select a
      suitable normalization technique to our data. This was then followed by PCA to
      reduce data dimensionality without losing the core characteristics of the data.
      Finally Cluster Analysis technique was applied to determine the number of
      clustered data with the aid of the CCC and Inconsistency Coefficient values.
      RESULTS: The outcome of a three-step analytical data classification process was
      the identification of seven distinctive forms of ILD functions. These seven ILD
      function classes were found to map to the four "known" ideal ILD sensitivity
      function types, namely: Sigmoidal-EI, Sigmoidal-IE, Peaked, and Insensitive, ILD
      functions, and variations within these classes. This indicates that these seven
      templates can be utilized in future modelling studies. CONCLUSIONS: We developed
      a taxonomy of ILD sensitivity functions using a methodological data
      classification approach. The number and types of generic ILD function patterns
      found with this method mapped well on to our electrophysiologically determined
      ILD sensitivity functions. While a larger data set of the latter functions may
      bring a more robust outcome, this good mapping is encouraging in providing a
      principled method for classifying such data sets, and could be well extended to
      other such neuronal sensitivity functions, such as contrast tuning in vision.

PMID- 24099095
TI  - Considering just noticeable difference in assessments of physical accommodation
      for product design.
AB  - Configuring products or environments for the size of their human users requires
      the consideration of several characteristics of the target user population,
      including body dimensions (anthropometry) and preferred interaction. Users are
      both adaptable and imperfect observers, which often makes it difficult for them
      to distinguish between candidate designs. This insensitivity is described by a
      concept called 'just noticeable difference', or JND. This paper presents an
      implementation of JND modelling and demonstrates how its use in the sizing of
      products or environments for target user populations can improve expected
      performance. Two facets of this problem are explored: (1) how experimental
      measures of JND for dimensional optimisation tasks may be obtained, and (2) how
      measures of JND may be included in models of user-device interaction for both
      adjustable and discretely sized products and the assumptions required. A case
      study demonstrating the collection and modelling of JND for a simple univariate
      problem is also presented. Practitioner Summary: Since people are adaptable and
      imperfect observers, there exists a 'just noticeable difference' that can be
      considered when designing products and environments. When JND is modelled for a
      target population, less variability in design dimensions due to physical user
      requirements may be necessary. This paper considers JND in quantitative
      simulations of population accommodation. 

PMID- 24099093
TI  - Silver nanowire exposure results in internalization and toxicity to Daphnia
      magna.
AB  - Nanowires (NWs), high-aspect-ratio nanomaterials, are increasingly used in
      technological materials and consumer products and may have toxicological
      characteristics distinct from nanoparticles. We carried out a comprehensive
      evaluation of the physicochemical stability of four silver nanowires (AgNWs) of
      two sizes and coatings and their toxicity to Daphnia magna . Inorganic aluminum
      doped silica coatings were less effective than organic poly(vinyl pyrrolidone)
      coatings at preventing silver oxidation or Ag(+) release and underwent a
      significant morphological transformation within 1 h following addition to low
      ionic strength Daphnia growth media. All AgNWs were highly toxic to D. magna but
      less toxic than ionic silver. Toxicity varied as a function of AgNW dimension,
      coating, and solution chemistry. Ag(+) release in the media could not account for
      observed AgNW toxicity. Single-particle inductively coupled plasma mass
      spectrometry distinguished and quantified dissolved and nanoparticulate silver in
      microliter-scale volumes of Daphnia magna hemolymph with a limit of detection of
      approximately 10 ppb. The silver levels within the hemolymph of Daphnia exposed
      to both Ag(+) and AgNW met or exceeded the initial concentration in the growth
      medium, indicating effective accumulation during filter feeding. Silver-rich
      particles were the predominant form of silver in hemolymph following exposure to
      both AgNWs and Ag(+). Scanning electron microscopy imaging of dried hemolymph
      found both AgNWs and silver precipitates that were not present in the AgNW stock
      or the growth medium. Both organic and inorganic coatings on the AgNW were
      transformed during ingestion or absorption. Pathway, gene ontology, and
      clustering analyses of gene expression response indicated effects of AgNWs
      distinct from ionic silver on Daphnia magna . 

PMID- 24099096
TI  - The contribution of maternal effects to selection response: an empirical test of
      competing models.
AB  - Maternal effects can dramatically influence the evolutionary process, in some
      cases facilitating and in others hindering adaptive evolution. Maternal effects
      have been incorporated into quantitative genetic models using two theoretical
      frameworks: the variance-components approach, which partitions variance into
      direct and maternal components, and the trait-based approach, which assumes that
      maternal effects are mediated by specific maternal traits. Here, we demonstrate
      parallels between these models and test their ability to predict evolutionary
      change. First, we show that the two approaches predict equivalent responses to
      selection in the absence of maternal effects mediated by traits that are
      themselves maternally influenced. We also introduce a correction factor that may
      be applied when such cascading maternal effects are present. Second, we use
      several maternal effect models, as well as the standard breeder's equation, to
      predict evolution in response to artificial selection on flowering time in
      American bellflower, Campanulastrum americanum. Models that included maternal
      effects made much more accurate predictions of selection response than the
      breeder's equation. Maternal effect models differed somewhat in their fit, with a
      version of the trait-based model providing the best fit. We recommend fitting
      such trait-based models when possible and appropriate to make the most accurate
      evolutionary predictions. 

PMID- 24099097
TI  - Interest in dietary pattern, social capital, and psychological distress: a cross
      sectional study in a rural Japanese community.
AB  - BACKGROUND: Among life-style factors affecting mental health, dietary habits are
      becoming a public health concern in their relation to psychological distress and
      social capital. We examined associations between interest in dietary pattern,
      social capital, and psychological distress with a population-based cross
      sectional study in rural Japan. METHODS: A total of 16,996 residents of a rural
      town in northern Japan aged 30-79 years participated in this questionnaire
      survey. The questionnaire gathered data about socio-demographic variables,
      psychological distress, issues related to dietary habits, including interest in
      dietary pattern, and the social capital factors of reciprocity and sense of
      community belonging. Factors related to psychological distress were analyzed by
      using multiple logistic regression analysis. RESULTS: A high interest in dietary
      pattern was significantly associated with a high level of social capital. In
      addition, an association between interest in dietary pattern and frequencies of
      intake of vegetables and fruits was confirmed. The multiple logistic regression
      analyses showed significant associations between interest in dietary pattern,
      social capital, frequency of intake of vegetables, and psychological distress
      after adjusting for socio-demographic variables. Low interest in dietary pattern
      was positively associated with psychological distress after adjusting for socio
      demographic variables (OR = 2.18; 95%CI: 1.69-2.81). Low levels of both
      reciprocity and sense of community belonging were associated with psychological
      distress after adjusting for socio-demographic variables (OR = 3.46 with 95%CI of
      2.10-5.71 for reciprocity, and OR = 7.42 with 95%CI of 4.64-11.87 for sense of
      community belonging). CONCLUSION: Low interest in dietary pattern, low frequency
      of intake of vegetables, and low levels of social capital were significantly
      associated with psychological distress after adjusting for socio-demographic
      variables.

PMID- 24099098
TI  - Cochrane diagnostic test accuracy reviews.
AB  - In 1996, shortly after the founding of The Cochrane Collaboration, leading
      figures in test evaluation research established a Methods Group to focus on the
      relatively new and rapidly evolving methods for the systematic review of studies
      of diagnostic tests. Seven years later, the Collaboration decided it was time to
      develop a publication format and methodology for Diagnostic Test Accuracy (DTA)
      reviews, as well as the software needed to implement these reviews in The
      Cochrane Library. A meeting hosted by the German Cochrane Centre in 2004 brought
      together key methodologists in the area, many of whom became closely involved in
      the subsequent development of the methodological framework for DTA reviews. DTA
      reviews first appeared in The Cochrane Library in 2008 and are now an integral
      part of the work of the Collaboration. 

PMID- 24099099
TI  - Generic medicines: an evaluation of the accuracy and accessibility of information
      available on the Internet.
AB  - BACKGROUND: Internationally, generic medicines are increasingly seen as a key
      strategy to reduce healthcare expenditure, therefore awareness and knowledge
      transfer regarding generic medicines are valid areas of research. Although the
      Internet is a frequently used source of medical information, the accuracy of
      material found online is variable. The aim of this study was to evaluate
      information provided on the Internet regarding generic medicines in terms of
      quality of information and readability. METHODS: Internet searches for
      information regarding generic medicine were completed, with a pre-defined search
      term, using the Google search engine, in five English-speaking geographical
      regions (US, UK, Ireland, Canada and Australia). Search results likely to be
      looked at by a searcher were collated and assessed for the quality of generic
      medicine-related information in the websites, using a novel customised Website
      Quality Assessment (WQA) tool; and for readability, using existing methods. The
      reproducibility of the tools between two independent reviewers was evaluated and
      correlations between WQA score, readability statistics and Google search engine
      results page ranking were assessed. RESULTS: Wikipedia was the highest-ranking
      search result in 100% of searches performed. Considerable variability of search
      results returned between different geographical regions was observed, including
      that websites identified in the Australian search generated the highest number of
      country specific websites; searches performed using computers with Irish,
      British, American and Canadian IP addresses appear to be more similar to each
      other than the google.com search performed in Australia; and the Canadian
      google.ca results show a notable difference from any of the other searches. Of
      the 24 websites assessed, none scored a perfect WQA score. Notably, strong
      correlation was seen between WQA and readability scores and ranking on google.com
      search results. CONCLUSIONS: This novel evaluation of websites providing
      information on generic medicines showed that, of the websites likely to be seen
      by a searcher, none demonstrated a combination of scoring highly on quality of
      information (as evinced by WQA score) and readability. Therefore, there is a gap
      in online knowledge provision on this topic which, if filled by a website
      designed using the WQA tool developed in this study, has an improved likelihood
      of ranking highly in google.com search results.

PMID- 24099101
TI  - Comparison of therapeutic effects between selective amygdalohippocampectomy and
      anterior temporal lobectomy for the treatment of temporal lobe epilepsy: a meta
      analysis.
AB  - BACKGROUND: Temporal lobe epilepsy (TLE) is a recurrent chronic nervous system
      disease. The conventional treatment is medicine. So far, anterior temporal
      lobectomy (ATL) and selective amygdalohippocampectomy (SAH) are becoming the two
      main approaches. METHODS: To compare the therapeutic effects between SAH and ATL
      in the treatment of temporal lobe epilepsy, we conducted a meta-analysis of
      published randomized controlled trials. The review applied the search strategy
      developed by the Cochrane Epilepsy Group and the Rev. Man 5.0 software to
      analyze. We also drew the forest plots with Risk Ratio (RR) as effect size. Six
      studies were eligible, with a total of 626 patients (337 patients with SAH and
      289 patients with ATL). RESULTS: There was no statistical significance of
      postoperative seizure control rate after 1 year, as well as the increase rate and
      decrease rate of verbal memory function between SAH and ATL. There is no
      statistical difference of therapeutic effects between SAH and ATL in the
      treatment of temporal lobe epilepsy. CONCLUSION: It is advised that clinically,
      physicians should choose the appropriate approach according to operation
      indications to improve the results of postoperative recovery.

PMID- 24099102
TI  - Primary osteosarcoma of clivus: a short report.
AB  - Next to multiple myeloma, osteosarcoma is the commonest primary malignant
      neoplasm of skeletal system. These are aggressive tumours, composed of spindle
      cells producing osteoid and rarely occur in calvaria. The authors report a 55
      year-male harbouring clival osteosarcoma, his clinical presentation, radiological
      findings, management and outcome.

PMID- 24099104
TI  - Detection of boronic acids through excited-state intramolecular proton-transfer
      fluorescence.
AB  - Boronic acids are versatile reagents for the chemical synthesis of organic
      molecules. They and other boron-containing compounds can be detected readily by
      the interruption of the excited-state intramolecular proton transfer (ESIPT) of
      10-hydroxybenzo[h]quinolone. This method is highly sensitive and selective, and
      useful for monitoring synthetic reactions and detecting boron-containing
      compounds on a solid support. 

PMID- 24099105
TI  - The innovative moments coding system and the assimilation of problematic
      experiences scale: a case study comparing two methods to track change in
      psychotherapy.
AB  - The Assimilation of Problematic Experiences Scale (APES) and the Innovative
      Moments Coding System were applied to transcripts of a successful case of
      linguistic therapy of evaluation independently by different research groups.
      Assimilation theory and research suggest that higher APES scores reflect
      therapeutic gains, with a level of approximately 4.0 separating good from poor
      outcome cases. The innovative moments (IMs) model suggests that IMs classified as
      reconceptualization and performing change occur mainly in good outcome cases,
      whereas action, reflection and protest occur in both good and poor outcome cases.
      Passages coded as reconceptualization and performing change were rare in this
      case, but 100% of them were rated at or above APES 4. By contrast, 63% passages
      coded as action, reflection or protest were rated below APES 4 (Chi-square =
      28.62, p < .001). Implications for research are discussed.

PMID- 24099106
TI  - Is problem-based learning an ideal format for developing ethical decision skills?
AB  - Ethical decision making is a complex process, which involves the interaction of
      knowledge, skills, and attitude. To enhance the teaching and learning on ethics
      reasoning, multiple teaching strategies have to be applied. A medical ethical
      reasoning (MER) model served as a framework of the development of ethics
      reasoning and their suggested instructional strategies. Problem-based learning
      (PBL), being used to facilitate students' critical thinking, self-directed
      learning, collaboration, and communication skills, has been considered effective
      on ethics education, especially when incorporated with experiential experience.
      Unlike lecturing that mainly disseminates knowledge and activates the left brain,
      PBL encourages "whole-brain" learning. However, PBL has several disadvantages,
      such as its inefficiency, lack of adequately trained preceptors, and the in
      depth, silo learning within a relatively small number of cases. Because each
      school tends to utilize PBL in different ways, either the curriculum designer or
      the learning strategy, it is important to maximize the advantages of a PBL
      session, PBL then becomes an ideal format for refining students' ethical
      decisions and behaviors. 

PMID- 24099107
TI  - Regulatory expression of MMP-8/MMP-9 and inhibition of proliferation, migration
      and invasion in human lung cancer A549 cells in the presence of HGF variants.
AB  - Hepatocyte growth factor (HGF), a potent cytokine of mesenchymal origin, exhibits
      polytrophic physiological responses, including proliferation, migration, and
      invasion, in a wide variety of cells. Although it is known that inhibition of the
      responses by HGF variants was via signal transducers and activators of the
      transcription pathway, the mechanisms of action of the variants involved in the
      production of matrix metalloproteinases (MMPs) were not clearly understood. Thus,
      recombinant HGF variants, NK1, NK2, NK3, and NK4 were topically applied to assays
      for proliferation, migration, invasion, and expression of MMPs in the human lung
      cancer cell line A549 and compared to that of control medium and a glutathione-s
      transferase control. Results showed that these recombinant HGF variants
      significantly inhibited proliferation, migration, and invasion of A549 at >4 nM,
      downregulated expression of MMP-9, and upregulated expression of MMP-8. The study
      clearly suggests that binding of the HGF variants to the cell surface c-Met
      resulted in the downregulation of MMP-9, and upregulation of MMP-8 protein
      expressions might be key molecular signals against proliferation, migration, and
      invasion of A549 cells. 

PMID- 24099103
TI  - The role of neutralizing antibodies in prevention of HIV-1 infection: what can we
      learn from the mother-to-child transmission context?
AB  - In most viral infections, protection through existing vaccines is linked to the
      presence of vaccine-induced neutralizing antibodies (NAbs). However, more than 30
      years after the identification of AIDS, the design of an immunogen able to induce
      antibodies that would neutralize the highly diverse HIV-1 variants remains one of
      the most puzzling challenges of the human microbiology. The role of antibodies in
      protection against HIV-1 can be studied in a natural situation that is the mother
      to-child transmission (MTCT) context. Indeed, at least at the end of pregnancy,
      maternal antibodies of the IgG class are passively transferred to the fetus
      protecting the neonate from new infections during the first weeks or months of
      life. During the last few years, strong data, presented in this review, have
      suggested that some NAbs might confer protection toward neonatal HIV-1 infection.
      In cases of transmission, it has been shown that the viral population that is
      transmitted from the mother to the infant is usually homogeneous, genetically
      restricted and resistant to the maternal HIV-1-specific antibodies. Although the
      breath of neutralization was not associated with protection, it has not been
      excluded that NAbs toward specific HIV-1 strains might be associated with a lower
      rate of MTCT. A better identification of the antibody specificities that could
      mediate protection toward MTCT of HIV-1 would provide important insights into the
      antibody responses that would be useful for vaccine development. The most
      convincing data suggesting that NAbs might confer protection against HIV-1
      infection have been obtained by experiments of passive immunization of newborn
      macaques with the first generation of human monoclonal broadly neutralizing
      antibodies (HuMoNAbs). However, these studies, which included only a few selected
      subtype B challenge viruses, provide data limited to protection against a very
      restricted number of isolates and therefore have limitations in addressing the
      hypervariability of HIV-1. The recent identification of highly potent second
      generation cross-clade HuMoNAbs provides a new opportunity to evaluate the
      efficacy of passive immunization to prevent MTCT of HIV-1.

PMID- 24099108
TI  - Intraoperative intracranial pressure and cerebral perfusion pressure for
      predicting surgical outcome in severe traumatic brain injury.
AB  - Intraoperative intracranial pressure (ICP) and cerebral perfusion pressure (CPP)
      were evaluated for use as prognostic indicators after surgery for severe
      traumatic brain injury (TBI), and threshold ICP and CPP values were determined to
      provide guidelines for patient management. This retrospective study reviewed data
      for 66 patients (20 females and 46 males) aged 13-83 years (average age, 48
      years) who had received decompressive craniectomy and hematoma evacuation for
      severe TBI. The analysis of clinical characteristics included Glascow Coma Scale
      score, trauma mechanism, trauma severity, cerebral hemorrhage type, hematoma
      thickness observed on computed tomography scan, Glasgow Outcome Scale score, and
      mortality. Patients whose treatment included ICP monitoring had significantly
      better prognosis (p < 0.001) and significantly lower mortality (p = 0.016)
      compared to those who did not receive ICP monitoring. At all three major steps of
      the procedure, i.e., creation of the burr hole, evacuation of the hematoma, and
      closing of the wound, intraoperative ICP and CPP values significantly differed.
      The ICP and CPP values were also significantly associated with surgical outcome
      in the severe TBI patients. Between hematoma evacuation and wound closure, ICP
      and CPP values differed by 6.8 +/- 4.5 and 6.5 +/- 4.6 mmHg, respectively (mean
      difference, 6 mmHg). Intraoperative thresholds were 14 mmHg for ICP and 56mmH for
      CPP. Monitoring ICP and CPP during surgery improves management of severe TBI
      patients and provides an early prognostic indicator. During surgery for severe
      TBI, early detection of increased ICP is also crucial for enabling sufficiently
      early treatment to improve surgical outcome. However, further study is needed to
      determine the optimal intraoperative ICP and CPP thresholds before their use as
      subjective guidelines for managing severe TBI patients. 

PMID- 24099109
TI  - Judging disease activity in rheumatoid arthritis by serum free kappa and lambda
      light chain levels.
AB  - The study aimed to evaluate the levels of serum free kappa (kappa) and lambda
      (lambda) light chains in patients with rheumatoid arthritis (RA) as well as
      exploring the association between serum free kappa and lambda light chains and
      activity of RA. For this purpose, healthy individuals and patients with active RA
      and RA in remission were enrolled, and their serum levels of free kappa and
      lambda light chains were measured using rate nephelometry. The diagnostic
      accuracy of serum free kappa and lambda light chains was evaluated by receiver
      operating characteristic curves and 95% confidence intervals for areas under the
      curve (AUC). The results obtained indicated that the levels of serum free kappa
      and lambda light chains in patients with active RA were significantly higher than
      those of patients in remission and of healthy controls (p < 0.05). Further, the
      AUC values in patients with active RA were 0.871 for free kappa light chain and
      0.781 for free lambda light chain. When the optimal cut-off point for serum kappa
      light chain was 8.02 g/L, the maximum sensitivity and specificity were 82.5% and
      82.5%, respectively, and when the optimal cut-off point for serum lambda light
      chain was 3.57 g/L, the maximum sensitivity and specificity were 80% and 82.5%,
      respectively. It was thus found that serum levels of free kappa and lambda light
      chains were positively correlated with disease activity in RA, the Disease
      Activity Score 28 (DAS28), and values for C-reactive protein (CRP), erythrocyte
      sedimentation rate (ESR), platelet count (PLT), rheumatoid factor (RF), and
      anticitrullinated protein antibody (ACPA) (p < 0.05). In conclusion, high serum
      levels of free kappa and lambda light chains in patients with active RA are
      closely correlated with disease activity parameters including DAS28, CRP, ESR,
      PLT, RF, and ACPA. Thus, the above-mentioned levels of serum free kappa and
      lambda light chains may be used as important indicators of activity of RA. 

PMID- 24099110
TI  - Patterns of recurrence and second primary tumors in oral squamous cell carcinoma
      treated with surgery alone.
AB  - The aim of the present study is to review the recurrence patterns and incidence
      of second primary tumors (SPTs) in patients with oral squamous cell carcinoma
      (OSCC) who underwent surgery alone without postoperative adjuvant therapy. Data
      on patients recorded in the head and neck cancer registry of Cathay General
      Hospital were reviewed. A total of 72 patients with T1-3N0 OSCC who underwent
      surgery alone were included. Among the 72 patients, 44 had T1 tumors, 22 had T2
      tumors, and 6 had T3 tumors. The 5-year overall survival (OS) rate was 77.3%, the
      recurrence-free survival rate was 74.1%, and the SPT-free survival rate was 73%.
      Eighteen (25%) patients had disease recurrence (regional recurrence in nine
      patients, local recurrence in seven patients, and locoregional recurrence in two
      patients). Most patients with local recurrence alone (6/7 patients, 85.7%) could
      be salvaged with treatment. However, locoregional control was obtained in only
      five (45.5%) of 11 patients with neck recurrence after surgical salvage therapy.
      At the time of analysis, 20 patients developed SPTs, and 15 (75%) of the SPTs
      were in the oral cavity. The annual incidence of SPT was 5%. Neck recurrence and
      SPT were associated with 48.4% and 24.4% lower 5-year OS rates, respectively.
      Multivariate analysis revealed that neck recurrence was a significant risk factor
      for low OS (p = 0.008). Neck recurrence was the most important prognostic factor
      for OS. The incidence of SPT development was high. Regular and long-term
      monitoring for recurrence and development of SPTs is necessary to improve the
      survival rate. 

PMID- 24099111
TI  - Combined effects of noise, vibration, and low temperature on the physiological
      parameters of labor employees.
AB  - Noise, vibration, and low temperature render specific occupational hazards to
      labor employees. The purpose of this research was to investigate the combined
      effects of these three physical hazards on employees' physiological parameters.
      The Taguchi experimental method was used to simulate different exposure
      conditions caused by noise, vibration, and low temperature, and their effects on
      the physiological parameters of the test takers were measured. The data were then
      analyzed using statistical methods to evaluate the combined effects of these
      three factors on human health. Results showed that the factor that influenced the
      finger skin temperature, manual dexterity, and mean artery pressure (MAP) most
      was air temperature, and exposure time was the second most influential factor.
      Noise was found to be the major factor responsible for hearing loss; in this
      case, hand-arm vibration and temperature had no effect at all. During the study,
      the temperature was confined in the 5-25 degrees C range (which was not
      sufficient to study the effects at extremely high- and low-temperature working
      conditions) because the combined effects of even two factors were very
      complicated. For example, the combined effects of hand-arm vibration and low
      temperature might lead to occupational hazards such as vibration-induced white
      finger syndrome in working labors. Further studies concerning the occupational
      damage caused by the combined effects of hazardous factors need to be conducted
      in the future. 

PMID- 24099113
TI  - Sudden death after medullary infarction - a case report.
AB  - Sudden death in a stable medullary infarction case frequently induces legal
      problems. Currently, the etiology of the most reported cases are not known
      because autopsy is rare. Here, we report one female patient with medullary
      infarction who experienced a sudden cardiopulmonary arrest during a brain
      magnetic resonance imaging (MRI) study. The blood flow changes on the MRI
      indicated that her death resulted from the sudden collapse of systemic
      circulation. Dysautonomia, or sudden respiratory arrest resulting from brainstem
      dysfunction, was suspected. In this report, we present her cranial MRI findings
      and discuss the possible pathophysiology after reviewing the relevant literature.
      We also recommend certain tests for patients with medullary infarction to prevent
      the risk of sudden unexpected deaths. 

PMID- 24099112
TI  - Bicondylar tibial plateau fracture treated by open reduction and fixation with
      unilateral locked plating.
AB  - The management of bicondylar tibial plateau fractures is challenging. A lateral
      locking plate offers an alternative method to traditional dual plating to avoid
      further stripping of soft tissue. Nevertheless, the rate of malreduction and
      fixation loss remains high. From 2007 to 2009, we performed open reduction and
      fixation with unilateral locked plating to directly reduce the fracture in 15
      patients with bicondylar plateau fracture. The average follow-up duration was
      16.2 months (range: 12-30 months), and the average age of the patients was 43
      years (range: 19-64 years). All fractures were Orthopaedic Trauma Association
      type 41-C. Postoperative radiographic alignment was evaluated immediately and at
      2-4 weeks, 8-12 weeks, 5-7 months, and 11-13 months. Both Oxford knee score and
      Hospital for Special Surgery knee score were used to evaluate functional
      outcomes. The average duration within which union was achieved was 4.8 months
      (range: 2-10 months). One patient incurred wound dehiscence; however, there was
      no case of deep infection. Malreduction occurred in one patient (6.7%) while
      fixation loss occurred in three patients (20%) with subsidence of the
      posteromedial fragment and varus malalignment. Despite the malreduction rate
      being lower in our study than in previous studies involving unilateral locked
      plating, a high rate of fixation loss was recorded. Per our limited experience,
      we believe that unilateral locked plating may have limitations in patients with
      selective patterns of bicondylar tibial plateau fractures. 

PMID- 24099114
TI  - Adult intussusception with perforation caused by hemangioma in the distal ileum.

PMID- 24099115
TI  - Alveolar rhabdomyosarcoma of the tunica vaginalis presenting as a tender
      hydrocele.

PMID- 24099116
TI  - Allergen immunotherapy for house dust mite: clinical efficacy and immunological
      mechanisms in allergic rhinitis and asthma.
AB  - INTRODUCTION: There is an increasing prevalence of atopic diseases such as
      allergic rhinitis and asthma with house dust mite (HDM) being the common allergen
      that is highly associated with allergic rhinitis and asthma. Allergen avoidance
      and pharmacotherapy are part of treatment but it has proved difficult to change
      the course of HDM-related allergic diseases. Allergen immunotherapy (AIT) has
      been in use for the past century and has been shown to be effective in the
      treatment of allergic respiratory disease. AREAS COVERED: This review exclusively
      focuses on HDM-AIT and discusses the differences in clinical efficacy and safety,
      long-term effect after discontinuation and immunological changes observed in both
      HDM-subcutaneous immunotherapy (SCIT) and HDM-sublingual immunotherapy (SLIT) in
      the treatment of allergic rhinitis and asthma in both pediatric and adult
      populations. EXPERT OPINION: The majority of studies involved small numbers of
      patients, variable doses of major allergens and are of variable quality. There is
      good evidence for HDM-SCIT efficacy and its long-term effect in adults and
      children, whereas at the present time, evidence for HDM-SLIT is unconvincing,
      particularly in children. In carefully selected patients, HDM-SCIT is effective
      and safe. More definitive trials are needed before HDM-SLIT can be recommended in
      routine practice for rhinitis and/or asthma.

PMID- 24099117
TI  - Managing personal health information in distributed research network
      environments.
AB  - BACKGROUND: Studying rare outcomes, new interventions and diverse populations
      often requires collaborations across multiple health research partners. However,
      transferring healthcare research data from one institution to another can
      increase the risk of data privacy and security breaches. METHODS: A working group
      of multi-site research programmers evaluated the need for tools to support data
      security and data privacy. The group determined that data privacy support tools
      should: 1) allow for a range of allowable Protected Health Information (PHI); 2)
      clearly identify what type of data should be protected under the Health Insurance
      Portability and Accountability Act (HIPAA); and 3) help analysts identify which
      protected health information data elements are allowable in a given project and
      how they should be protected during data transfer. Based on these requirements we
      developed two performance support tools to support data programmers and site
      analysts in exchanging research data. RESULTS: The first tool, a workplan
      template, guides the lead programmer through effectively communicating the
      details of multi-site programming, including how to run the program, what output
      the program will create, and whether the output is expected to contain protected
      health information. The second performance support tool is a checklist that site
      analysts can use to ensure that multi-site program output conforms to
      expectations and does not contain protected health information beyond what is
      allowed under the multi-site research agreements. CONCLUSIONS: Together the two
      tools create a formal multi-site programming workflow designed to reduce the
      chance of accidental PHI disclosure.

PMID- 24099119
TI  - Pd(II)-catalyzed Ph2(O)P-directed C-H olefination toward phosphine-alkene
      ligands.
AB  - The Pd(II)-catalyzed Ph2(O)P-directed C-H olefination to synthesize alkene
      phosphine compounds is reported. In contrast to previous examples of various
      directing groups that guide selective C-H activation, the Ph2(O)P group not only
      acts as the directing group but also serves to construct the alkene-phosphine
      ligands. The monoprotected amino acid (MPAA) ligand Ac-Leu-OH is found to promote
      this reaction in a significant manner. 

PMID- 24099118
TI  - Procyanidins from evening primrose (Oenothera paradoxa) defatted seeds inhibit
      invasiveness of breast cancer cells and modulate the expression of selected genes
      involved in angiogenesis, metastasis, and apoptosis.
AB  - There is a growing interest in plant polyphenols (including flavanols) that
      exhibit pleiotropic biological activities such as antiinflammatory, antioxidant,
      and anticancer effects. Here, we report for the first time the inhibition of MDA
      MB-231 breast cancer cell viability and invasiveness by an evening primrose
      flavanol preparation (EPFP). We observed a decrease in MDA-MB-231 viability of
      50% vs. a control after 72 h of incubation with EPFP at a concentration of 58 MUM
      gallic acid equivalents (GAE) and an inhibition of their invasiveness of 65% vs.
      a control at 75 MUM GAE after 48 h of incubation. EPFP caused a 10-fold reduction
      in matrix metalloproteinase-9 (MMP-9) activity at 100 MUM GAE. Furthermore,
      through modulation of mRNA expression, EPFP reduced the expression levels of the
      following proteins: antiapoptotic Bcl-2, angiogenic vascular endothelial growth
      factor (VEGF), and 2 transcription factors (c-Jun, c-Fos). Moreover, analysis by
      flow cytometry revealed that EPFP induced apoptosis in MDA-MB-231 cells. In
      conclusion, our data shows that EPFP inhibits cell viability by increasing
      apoptosis and decreases cell invasiveness by decreasing angiogenesis.

PMID- 24099120
TI  - NBD-labeled cholesterol analogues in phospholipid bilayers: insights from
      molecular dynamics.
AB  - Nitrobenzoxadiazole (NBD)-labeled sterols are commonly used as fluorescent
      cholesterol analogues in membrane biophysics. However, some experimental reports
      have questioned their ability to emulate the behavior of cholesterol in
      phospholipid bilayers. For the purpose of a detailed clarification of this
      matter, atomistic molecular dynamics simulations of 1-palmitoyl-2-oleoyl-sn
      glycero-3-phosphocholine (POPC) bilayers, containing either cholesterol or one of
      two fluorescent cholesterol analogues, 22-NBD-cholesterol or 25-NBD-cholesterol,
      were carried out. It is found that these sterol probes tend to adopt
      conformations in which their tail-labeled fluorophore is oriented toward the
      lipid/water interface, with a location similar to that observed in molecular
      dynamics simulations of other NBD probes. This implies that in these molecules
      the long sterol axis is no longer aligned with the membrane normal, and
      preferentially adopts orientations approximately parallel to the bilayer plane.
      In turn, these stretched conformations, together with NBD-POPC atomic
      interactions, lead to slowed-down lateral diffusion of both fluorescent sterols,
      compared to cholesterol. From computation of the deuterium order parameter and
      acyl chain tilts of POPC chains for varying POPC-sterol distance, it is observed
      that the local ordering effect of sterol is altered in both fluorescent
      derivatives. In agreement with reported experimental data, both fluorescent
      sterols are able to increase the order of POPC at 20 mol % concentration (as some
      molecules adopt an upright conformation, possibly related to formation of
      transbilayer aggregates), albeit to a smaller extent to that of cholesterol.
      Altogether, this study indicates that both 22- and 25-NBD-cholesterol are unable
      to mimic the most important features of cholesterol's behavior in lipid bilayers.

PMID- 24099121
TI  - Acute appendicitis: is it time to reassess best management?

PMID- 24099122
TI  - Re: evaluating the value and impact of the Victorian Audit of Surgical Mortality.

PMID- 24099123
TI  - Response to re: evaluating the value and impact of the Victorian Audit of
      Surgical Mortality.

PMID- 24099124
TI  - Guy de Chauliac: pre-eminent surgeon of the Middle Ages.
AB  - Guy de Chauliac (c1300-1368) trained in Toulouse and the University of
      Montpellier from where he achieved the highest possible degree of Master of
      medicine. He undertook fellowships in Bologna (anatomical dissection) and Paris
      (surgery) and was qualified as a physician not a Barber Surgeon. He took Holy
      Orders and was appointed as physician to three Avignon-based Popes. He survived
      an epidemic of the Black Death (1348-1350), suffering an axillary bubo. His book
      Chirugia Magna was written in medieval Latin in 1363, then circulated in
      manuscript form before its first printing in 1478. There were 70 editions as it
      became the most influential surgical text for over 200 years, particularly in
      France, spanning the period from the late 14th century until Pare (1510-1590). He
      divided surgery into swellings, wounds, ulcers, fractures and dislocations, and
      special diseases. Well researched and referenced, based on evidence and
      experience, he succeeded in incorporating antiquarian and contemporary thinking
      from French, Arabian, Italian (Bologna), Egyptian and Greek scholars about
      anatomy, surgical disease and treatment. He was a strong advocate for evaluating
      outcomes, knowing when not to operate, professionalism and the non-technical
      competencies. His framework of professionalism was based on four domains: being
      learned, expert, ingenious and adaptable. The surgical aspirants and leaders of
      the following two centuries recognized the academic, professional and practical
      value of his teaching through their reference to and use of Chirugia Magna. The
      Cowlishaw collection in the Royal Australasian College of Surgeons' library
      contains four French copies, under the title La Grande Chirugie. 

PMID- 24099125
TI  - Impact of an acute care surgery model on appendicectomy outcomes.
AB  - BACKGROUND: Monash Medical Centre introduced the acute surgical unit (ASU) in
      July 2011. The ASU is modelled on the concept of acute care surgery (ACS). This
      study reviews the impact of the ASU on the outcomes in an appendicectomy
      population. METHODS: A retrospective review of all patients (aged 16-99 years)
      who underwent appendicectomies in the 2-year study time frame (from July 2010 to
      June 2012) at our centre was performed. The cohort (n = 539) was divided into two
      groups for analysis: the ASU group, patients admitted on or after 18 July 2011 (n
      = 283), and the control group, patients admitted prior to 18 July 2011 (n = 256).
      RESULTS: Median time to operation (1129 min versus 1080 min, P = 0.963) and
      negative appendicectomy rate (24.2% versus 24.8%, P = 0.871) were similar in both
      groups. The proportion of operations performed overnight (18.00-08.00 hours) was
      significantly decreased in the ASU group (17.1% versus 30.7%, P < 0.001).
      Perforation rate was marginally higher in the ASU group (17.8% versus 11.8%, P =
      0.053) but failed to reach statistical significance. There was an increase in the
      usage of preoperative imaging (40.3% versus 30.5%, P = 0.018) in the ASU group.
      Operating times, length of stay, laparoscopic-to-open conversion and surgical
      site infection rates remained similar. CONCLUSION: We conclude that
      implementation of an ACS model does not lead to objective differences in outcome
      for patients after appendicectomy. However, the ACS model significantly decreased
      the number of operations performed after-hours.

PMID- 24099126
TI  - Comparison of appendicectomy outcomes: acute surgical versus traditional pathway.
AB  - INTRODUCTION: The acute surgical unit (ASU) is an evolving novel concept
      introduced to address the challenge of maintaining key performance indicators
      (KPIs) in the face of an increasing acute workload. METHODS: The aim of this
      retrospective study was to compare the performance of the ASU (from June 2008 to
      December 2010) at Auckland City Hospital with the traditional model (from January
      2006 to May 2008) and benchmark the results against other similar published
      studies. The analysis was on the basis of KPIs for 1857 appendicectomies, which
      form a large volume of acute surgical presentations. RESULTS: Our results show
      significant improvement in length of stay (2.8 days, 2.6 days, P = 0.0001) and
      proportion of daytime operations (59.4%, 65.8%, P = 0.004), in keeping with other
      studies on benchmarking. CONCLUSION: The introduction of ASU has led to
      significant improvements in some KPIs for appendicectomy outcomes in the face of
      an increasing workload.

PMID- 24099127
TI  - Small bowel injury from suction drain after laparoscopic appendicectomy.

PMID- 24099128
TI  - Mucinous adenocarcinoma of the appendix in a hernia of Morgagni: a unique case
      report.

PMID- 24099129
TI  - Splash! The spontaneous rupture of a bladder diverticulum: a rare cause of an
      acute abdomen.

PMID- 24099130
TI  - Chondrosarcoma in a patient with osteogenesis imperfecta.

PMID- 24099131
TI  - Re: history of lower limb reconstruction after trauma.

PMID- 24099132
TI  - Re: Bugosa hernia: a hernia of the conjoint tendon.

PMID- 24099133
TI  - Influence of natural organic matter fouling and osmotic backwash on pressure
      retarded osmosis energy production from natural salinity gradients.
AB  - Pressure retarded osmosis (PRO) has the potential to produce clean, renewable
      energy from natural salinity gradients. However, membrane fouling can lead to
      diminished water flux productivity, thus reducing the extractable energy. This
      study investigates organic fouling and osmotic backwash cleaning in PRO and the
      resulting impact on projected power generation. Fabricated thin-film composite
      membranes were fouled with model river water containing natural organic matter.
      The water permeation carried foulants from the feed river water into the membrane
      porous support layer and caused severe water flux decline of ~46%. Analysis of
      the water flux behavior revealed three phases in membrane support layer fouling.
      Initial foulants of the first fouling phase quickly adsorbed at the active
      support layer interface and caused a significantly greater increase in hydraulic
      resistance than the subsequent second and third phase foulants. The water
      permeability of the fouled membranes was lowered by ~39%, causing ~26% decrease
      in projected power density. A brief, chemical-free osmotic backwash was
      demonstrated to be effective in removing foulants from the porous support layer,
      achieving ~44% recovery in projected power density. The substantial performance
      recovery after cleaning was attributed to the partial restoration of the membrane
      water permeability. This study shows that membrane fouling detrimentally impacts
      energy production, and highlights the potential strategies to mitigate fouling in
      PRO power generation with natural salinity gradients. 

PMID- 24099134
TI  - An International Menopause Society study of climate, altitude, temperature (IMS
      CAT) and vasomotor symptoms in urban Indian regions.
AB  - OBJECTIVE: To examine the relationships between climate (season, temperature,
      humidity), lifestyle, health, mood and beliefs and experience of hot flushes and
      night sweats amongst mid-aged women living in eight urban Indian centers.
      METHODS: A total of 717 peri- and postmenopausal women, aged 45-55 years, from
      urban centers in different regions of India were included. Data were collected
      during both summer and winter months. Participants completed questionnaires
      eliciting information about sociodemographics, hot flushes (prevalence, frequency
      and problem-rating), health and lifestyle (body mass index, diet, exercise,
      alcohol use), mood (Women's Health Questionnaire) and attributions and beliefs
      (Menopause Representations Questionnaire). RESULTS: The prevalence of vasomotor
      symptoms was low, with 34% of the sample reporting hot flushes and/or night
      sweats. Seasonal variation in temperature was not associated with hot flush
      prevalence, frequency or problem rating. Hot flush prevalence was mainly
      associated with higher anxiety and intake of spicy foods, frequency with (older)
      age and (more) frequent exercise, while hot flushes were more problematic for
      women who reported poorer general health and more negative beliefs about
      menopause. CONCLUSIONS: In this study of Indian women, seasonal temperature
      variation did not appear to influence hot flush reporting. Health, mood, beliefs
      and lifestyle factors appear to explain some, but not all, of the variance in
      experience of menopausal symptoms.

PMID- 24099135
TI  - Parenteral and oral antibiotic duration for treatment of pediatric osteomyelitis:
      a systematic review protocol.
AB  - BACKGROUND: Pediatric osteomyelitis is a bacterial infection of bones requiring
      prolonged antibiotic treatment using parenteral followed by enteral agents. Major
      complications of pediatric osteomyelitis include transition to chronic
      osteomyelitis, formation of subperiosteal abscesses, extension of infection into
      the joint, and permanent bony deformity or limb shortening. Historically,
      osteomyelitis has been treated with long durations of antibiotics to avoid these
      complications. However, with improvements in management and antibiotic treatment,
      standard of care is moving towards short durations of intravenous antibiotics
      prior to enteral antibiotics. METHODS/DESIGN: The authors will perform a
      systematic review based on PRISMA guidelines in order to evaluate the literature,
      looking for evidence to support the optimal duration of parenteral and enteral
      therapy. The main goals are to see if literature supports shorter durations of
      either parenteral antibiotics and/or enteral antibiotics.Multiple databases will
      be investigated using a thorough search strategy. Databases include Medline,
      Cochrane, EMBASE, SCOPUS, Dissertation Abstracts, CINAHL, Web of Science, African
      Index Medicus and LILACS. Search stream will include medical subject heading for
      pediatric patients with osteomyelitis and antibiotic therapy. We will search for
      published or unpublished randomized and quasi-randomized controlled trials.Two
      authors will independently select articles, extract data and assess risk of bias
      by standard Cochrane methodologies. We will analyze comparisons between
      dichotomous outcomes using risk ratios and continuous outcomes using mean
      differences. 95% confidence intervals will be computed. DISCUSSION: One of the
      major dilemmas of management of this disease is the duration of parenteral
      therapy. Long parenteral therapy has increased risk of serious complications and
      the necessity for long therapy has been called into question. Our study aims to
      review the currently available evidence from randomized trials regarding duration
      of both parenteral and oral therapy for pediatric acute osteomyelitis. TRIAL
      REGISTRATION: CRD42013002320.

PMID- 24099136
TI  - gp130: a promising drug target for cancer therapy.
AB  - INTRODUCTION: Ubiquitously expressed in the human body, glycoprotein 130 (gp130)
      is a shared subunit of receptor complexes for at least nine cytokines (IL-6, OSM,
      LIF, IL-11, CNTF, CLC, IL-27, CT-1, and NP) that mediate highly diverse
      biological processes. Dysregulation of gp130 expression, activation, or
      associated signaling pathways are implicated in a variety of human diseases,
      including cancer. Accumulating evidence indicates that the gp130-mediated
      signaling networks play important roles in the progression of multiple types of
      cancer. AREAS COVERED: This review discusses the structural basis of gp130 in
      signal transduction activity and its role in physiological and pathological
      conditions, particularly cancer. We analyzed the currently available databases to
      illustrate the expression of gp130, its coexpression with other molecules
      involved in the gp130 signaling pathways, and the role of gp130 in cancer
      progression. Finally, we highlight strategies for blocking gp130 signaling and
      the currently available antagonists. EXPERT OPINION: As gp130 signaling mediates
      cancer progression, inhibition of gp130 activity offers a potential and promising
      approach to cancer therapy. Compared to antibodies blocking individual cytokines,
      gp130-targeted small-molecule inhibitors present multiple advantages. To achieve
      successful clinical outcomes for gp130-targeted cancer therapy, dosage
      determination, duration of therapy, and patient selection are some of the
      critical factors to be considered.

PMID- 24099137
TI  - Signaling efficacy drives the evolution of larger sexual ornaments by sexual
      selection.
AB  - Why are there so few small secondary sexual characters? Theoretical models
      predict that sexual selection should lead to reduction as often as exaggeration,
      and yet we mainly associate secondary sexual ornaments with exaggerated features
      such as the peacock's tail. We review the literature on mate choice experiments
      for evidence of reduced sexual traits. This shows that reduced ornamentation is
      effectively impossible in certain types of ornamental traits (behavioral,
      pheromonal, or color-based traits, and morphological ornaments for which the
      natural selection optimum is no trait), but that there are many examples of
      morphological traits that would permit reduction. Yet small sexual traits are
      very rarely seen. We analyze a simple mathematical model of Fisher's runaway
      process (the null model for sexual selection). Our analysis shows that the
      imbalance cannot be wholly explained by larger ornaments being less costly than
      smaller ornaments, nor by preferences for larger ornaments being less costly than
      preferences for smaller ornaments. Instead, we suggest that asymmetry in
      signaling efficacy limits runaway to trait exaggeration. 

PMID- 24099138
TI  - Stress eating and tuning out: cancer cells re-wire metabolism to counter stress.
AB  - Cancer cells reprogram metabolism to maintain rapid proliferation under often
      stressful conditions. Glycolysis and glutaminolysis are two central pathways that
      fuel cancer metabolism. Allosteric regulation and metabolite driven post
      translational modifications of key metabolic enzymes allow cancer cells
      glycolysis and glutaminolysis to respond to changes in nutrient availability and
      the tumor microenvironment. While increased aerobic glycolysis (the Warburg
      effect) has been a noted part of cancer metabolism for over 80 years, recent work
      has shown that the elevated levels of glycolytic intermediates are critical to
      cancer growth and metabolism due to their ability to feed into the anabolic
      pathways branching off glycolysis such as the pentose phosphate pathway and
      serine biosynthesis pathway. The key glycolytic enzymes phosphofructokinase-1
      (PFK1), pyruvate kinase (PKM2) and phosphoglycerate mutase 1 (PGAM1) are
      regulated by upstream and downstream metabolites to balance glycolytic flux with
      flux through anabolic pathways. Glutamine regulation is tightly controlled by
      metabolic intermediates that allosterically inhibit and activate glutamate
      dehydrogenase, which fuels the tricarboxylic acid cycle by converting glutamine
      derived glutamate to alpha-ketoglutarate. The elucidation of these key allosteric
      regulatory hubs in cancer metabolism will be essential for understanding and
      predicting how cancer cells will respond to drugs that target metabolism.
      Additionally, identification of the structures involved in allosteric regulation
      will inform the design of anti-metabolism drugs which bypass the off-target
      effects of substrate mimics. Hence, this review aims to provide an overview of
      allosteric control of glycolysis and glutaminolysis.

PMID- 24099139
TI  - Aroma characterization of chinese rice wine by gas chromatography-olfactometry,
      chemical quantitative analysis, and aroma reconstitution.
AB  - The aroma profile of Chinese rice wine was investigated in this study. The
      volatile compounds in a traditional Chinese rice wine were extracted using
      Lichrolut EN and further separated by silica gel normal phase chromatography.
      Seventy-three aroma-active compounds were identified by gas chromatography
      olfactometry (GC-O) and gas chromatography-mass spectrometry (GC-MS). In addition
      to acids, esters, and alcohols, benzaldehyde, vanillin, geosmin, and gamma
      nonalactone were identified to be potentially important to Chinse rice wine. The
      concentration of these aroma-active compounds in the Chinese rice wine was
      further quantitated by combination of four different methods, including headsapce
      gas chromatography, solid phase microextraction-gas chromatography (SPME)-GC-MS,
      solid-phase extraction-GC-MS, and SPME-GC-pulsed flame photometric detection
      (PFPD). Quantitative results showed that 34 aroma compounds were at
      concentrations higher than their corresponding odor thresholds. On the basis of
      the odor activity values (OAVs), vanillin, dimethyl trisulfide, beta-phenylethyl
      alcohol, guaiacol, geosmin, and benzaldehyde could be responsible for the unique
      aroma of Chinese rice wine. An aroma reconstitution model prepared by mixing 34
      aroma compounds with OAVs > 1 in an odorless Chinese rice wine matrix showed a
      good similarity to the aroma of the original Chinese rice wine. 

PMID- 24099140
TI  - Chronic disease prevention policy in British Columbia and Ontario in light of
      public health renewal: a comparative policy analysis.
AB  - BACKGROUND: Public health strategies that focus on legislative and policy change
      involving chronic disease risk factors such as unhealthy diet and physical
      inactivity have the potential to prevent chronic diseases and improve quality of
      life as a whole. However, many public health policies introduced as part of
      public health reform have not yet been analyzed, such as in British Columbia and
      Ontario. The purpose of this paper is to present the results of a descriptive,
      comparative analysis of public health policies related to the Healthy Living Core
      Program in British Columbia and Chronic Disease Prevention Standard in Ontario
      that are intended to prevent a range of chronic diseases by promoting healthy
      eating and physical activity, among other things. METHODS: Policy documents were
      found through Internet search engines and Ministry websites, at the guidance of
      policy experts. These included government documents as well as documents from non
      governmental organizations that were implementing policies and programs at a
      provincial level. Documents (n = 31) were then analysed using thematic content
      analysis to classify, describe and compare policies in a systematic fashion,
      using the software NVivo. RESULTS: Three main categories emerged from the
      analysis of documents: 1) goals for chronic disease prevention in British
      Columbia and Ontario, 2) components of chronic disease prevention policies, and
      3) expected outputs of chronic disease prevention interventions. Although there
      were many similarities between the two provinces, they differed somewhat in terms
      of their approach to issues such as evidence, equity, and policy components. Some
      expected outputs were adoption of healthy behaviours, use of information, healthy
      environments and increased public awareness. CONCLUSIONS: The two provincial
      policies present different approaches to support the implementation of related
      programs. Differences may be related to contextual factors such as program
      delivery structures and different philosophical approaches underlying the two
      frameworks. These differences and possible explanations for them are important to
      understand because they serve to contextualize the differences in health outcomes
      across the two provinces that might eventually be observed. This analysis informs
      future public health policy directions as the two provinces can learn from each
      other.

PMID- 24099141
TI  - EEG biofeedback improves attentional bias in high trait anxiety individuals.
AB  - BACKGROUND: Emotion-related attentional bias is implicated in the aetiology and
      maintenance of anxiety disorders. Electroencephalogram (EEG) biofeedback can
      obviously improve the anxiety disorders and reduce stress level, and can also
      enhance attention performance in healthy subjects. The present study examined the
      effects and mechanisms of EEG biofeedback training on the attentional bias of
      high trait anxiety (HTA) individuals toward negative stimuli. RESULTS: Event
      related potentials were recorded while HTA (n=24) and nonanxious (n=21)
      individuals performed the color-word emotional Stroop task. During the emotional
      Stroop task, HTA participants showed longer reaction times and P300 latencies
      induced by negative words, compared to nonanxious participants.The EEG
      biofeedback significantly decreased the trait anxiety inventory score and
      reaction time in naming the color of negative words in the HTA group. P300
      latencies evoked by negative stimuli in the EEG biofeedback group were
      significantly reduced after the alpha training, while no significant changes were
      observed in the sham biofeedback group after the intervention. CONCLUSION: The
      prolonged P300 latency is associated with attentional bias to negative stimuli in
      the HTA group. EEG biofeedback training demonstrated a significant improvement of
      negative emotional attentional bias in HTA individuals, which may be due to the
      normalization of P300 latency.

PMID- 24099142
TI  - WAIS-IV reliable digit span is no more accurate than age corrected scaled score
      as an indicator of invalid performance in a veteran sample undergoing evaluation
      for mTBI.
AB  - Reliable Digit Span (RDS) is a measure of effort derived from the Digit Span
      subtest of the Wechsler intelligence scales. Some authors have suggested that the
      age-corrected scaled score provides a more accurate measure of effort than RDS.
      This study examined the relative diagnostic accuracy of the traditional RDS, an
      extended RDS including the new Sequencing task from the Wechsler Adult
      Intelligence Scale-IV, and the age-corrected scaled score, relative to
      performance validity as determined by the Test of Memory Malingering. Data were
      collected from 138 Veterans seen in a traumatic brain injury clinic. The
      traditional RDS (<= 7), revised RDS (<= 11), and Digit Span age-corrected scaled
      score ( <= 6) had respective sensitivities of 39%, 39%, and 33%, and respective
      specificities of 82%, 89%, and 91%. Of these indices, revised RDS and the Digit
      Span age-corrected scaled score provide the most accurate measure of performance
      validity among the three measures.

PMID- 24099143
TI  - In vivo safety evaluation of polyarginine coated magnetic nanovectors.
AB  - Safety and efficacy are of critical importance to any nanomaterial-based
      diagnostic and therapy. The innocuity and functionality of a nanomaterial in vivo
      is largely dependent on the physicochemical properties of the material,
      particularly its surface coating. Here, we evaluated the influence of
      polycationic coating on the efficacy, clearance organ uptake, and safety of
      magnetic nanovectors designed for siRNA delivery. Polyethylene glycol (PEG)
      coated superparamagnetic iron oxide nanoparticles (NPs) of 12 nm in core diameter
      were modified with a polycationic coating of either poly-l-arginine (pArg) or
      polyethylenimine (PEI) and further covalently functionalized with siRNA
      oligonucleotides. The produced NP-pArg-siRNA and NP-PEI-siRNA nanovectors were
      similar in hydrodynamic size (21 and 22 nm, respectively) but significantly
      differed in zeta potentials (+2.1 mV and +29.8 mV, respectively). Fluorescence
      quantification assays revealed that the NP-pArg-siRNA nanovector was 3-fold more
      potent than NP-PEI-siRNA in delivering siRNA and 1.8-fold more effective in gene
      silencing when tested in rat C6 glioblastoma cells. In vivo, both nanovector
      formulations were similarly taken up by the spleen and liver as determined by
      histopathological and hemopathological assays. However, PEI coated nanovectors
      elicited severe hemoincompatibility and damage to the liver and spleen, while
      pArg coated nanovectors were found to be safe and tolerable. Combined, our
      findings suggest that polycationic coatings of pArg were more effective and safer
      than commonly used PEI coatings for preparation of nanovectors. The NP-pArg-siRNA
      nanovector formulation developed here shows great potential for in vivo based
      biomedical applications. 

PMID- 24099144
TI  - Optimization on preparation condition of polyunsaturated fatty acids nanoliposome
      prepared by Mozafari method.
AB  - This study presents the application of the response surface methodology (design)
      to develop an optimal preparation condition (independent variables) namely shear
      rate (600-1000 rpm), mixing time (30-60 min), and sonication time (10-20 min) for
      polyunsaturated fatty acids (docosahexaenoic acid and eicosapentaenoic acid)
      nanoliposomes. Fifteen lipid mixtures were generated by the Box-Behnken design
      and nanoliposomes were prepared by the Mozafari (direct hydration and without
      using organic solvents) method. Nanoliposomes were characterized with respect to
      entrapment efficiency (EE) and vesicle size as Y1 and Y2 dependent variables,
      respectively. The results were then applied to estimate the coefficients of
      response surface model and to find the optimal preparation conditions with
      maximum EE and minimum vesicle size. The response surface analysis exhibited that
      the significant (p < 0.05) second-order polynomial regression equations were
      successfully fitted for all dependent variables with no significant (p > 0.05)
      lack of fit for the reduced models. The response optimization of experiments was
      the shear rate: 795 rpm; mixing time: 60 min; and sonication time: 10 min. The
      optimal nanoliposome had an average diameter of 81.4 nm and EE of 100%. The
      experimental results of optimal nanoliposomes characterization confirmed an
      accurate fitness of the predicted values by reduced response surface models.

PMID- 24099145
TI  - A qualitative study of the perceived effects of blue lights in washrooms on
      people who use injection drugs.
AB  - BACKGROUND: Blue lights are sometimes placed in public washrooms to discourage
      injection drug use. Their effectiveness has been questioned and concerns raised
      that they are harmful but formal research on the issue is limited to a single
      study. We gathered perceptions of people who use injection drugs on the effects
      of blue lights with the aim of informing harm reduction practice. METHODS: We
      interviewed 18 people in two Canadian cities who currently or previously used
      injection drugs to better understand their perceptions of the rationale for and
      consequences of blue lights in public washrooms. RESULTS: Participants described
      a preference for private places to use injection drugs, but explained that the
      need for an immediate solution would often override other considerations. While
      public washrooms were in many cases not preferred, their accessibility and
      relative privacy appear to make them reasonable compromises in situations
      involving urgent injecting. Participants understood the aim of blue lights to be
      to deter drug use. The majority had attempted to inject in a blue-lit washroom.
      While there was general agreement that blue lights do make injecting more
      difficult, a small number of participants were entirely undeterred by them, and
      half would use a blue-lit washroom if they needed somewhere to inject urgently.
      Participants perceived that, by making veins less visible, blue lights make
      injecting more dangerous. By dispersing public injection drug use to places where
      it is more visible, they also make it more stigmatizing. Despite recognizing
      these harms, more than half of the participants were not opposed to the continued
      use of blue lights. CONCLUSIONS: Blue lights are unlikely to deter injection
      drugs use in public washrooms, and may increase drug use-related harms. Despite
      recognizing these negative effects, people who use injection drugs may be
      reluctant to advocate against their use. We attempt to reconcile this apparent
      contradiction by interpreting blue lights as a form of symbolic violence and
      suggest a parallel with other emancipatory movements for inspiration in
      advocating against this and other oppressive interventions.

PMID- 24099146
TI  - Morphologically robust NiFe2O4 nanofibers as high capacity Li-ion battery anode
      material.
AB  - In this work, the electrochemical performance of NiFe2O4 nanofibers synthesized
      by an electrospinning approach have been discussed in detail. Lithium storage
      properties of nanofibers are evaluated and compared with NiFe2O4 nanoparticles by
      galvanostatic cycling and cyclic voltammetry studies, both in half-cell
      configurations. Nanofibers exhibit a higher charge-storage capacity of 1000 mAh
      g(-1) even after 100 cycles with high Coulmbic efficiency of 100% between 10 and
      100 cycles. Ex situ microscopy studies confirmed that cycled nanofiber electrodes
      maintained the morphology and remained intact even after 100 charge-discharge
      cycles. The NiFe2O4 nanofiber electrode does not experience any structural stress
      and eventual pulverisation during lithium cycling and hence provides an efficient
      electron conducting pathway. The excellent electrochemical performance of NiFe2O4
      nanofibers is due to the unique porous morphology of continuous nanofibers.

PMID- 24099147
TI  - Detection of Chlamydophila pneumoniae and human herpesvirus 8 in primary
      cutaneous anaplastic large-cell lymphoma: a case report.
AB  - BACKGROUND: The etiology of primary cutaneous anaplastic large-cell CD30+
      lymphoma is largely unknown, and although an infectious involvement has been
      suspected, the implication of infectious agents in its pathogenesis is still
      unclear. FINDINGS: We report the case of a HIV-negative patient referred to our
      hospital with a rapidly enlarging skin tumor on her upper eyelid. Surgical
      excision was performed and histological analysis evidenced a primary cutaneous
      anaplastic large-cell lymphoma. Due to the ocular localization and to the
      prominent angiogenic component of the lesion, molecular analyses for the
      detection of Chlamydophila pneumoniae and HHV8 were performed, revealing the
      presence of an infection by both pathogens in surgical biopsy and in peripheral
      blood mononuclear cells. CONCLUSIONS: These findings suggest for the first time a
      possible association of C. pneumoniae and/or HHV8 infection, or both together,
      with primary cutaneous anaplastic large-cell lymphoma in non-immunocompromised
      and HIV-negative subjects. This potential pathogenic association, if confirmed,
      could provide potential indications for future therapy.

PMID- 24099148
TI  - Balancing efficacy against safety in sublingual immunotherapy with inhalant
      allergens: what is the best approach?
AB  - Over the last 20 years, studies and clinical trials have demonstrated efficacy,
      safety and cost-effectiveness of sublingual immunotherapy (SLIT) for respiratory
      allergic diseases. Nevertheless, it seems to be mostly used as a second-line
      therapeutic option, and adherence to treatment is not always optimal. Selective
      literature research was done in Medline and PubMed, including guidelines,
      position papers and Cochrane meta-analyses concerning SLIT in adult patients. The
      most recent reviews confirm SLIT as viable and efficacious treatment especially
      for allergic rhinitis, even if the optimal dosage, duration, schedule are not
      clearly established for most of the products. Despite an optimal safety profile,
      tolerability and patient-reported outcomes concerning SLIT have received poor
      attention until now. Recently, new tools have been specifically developed in
      order to investigate these aspects. Regular assessment of tolerability profile
      and SLIT-related patient-reported outcomes will allow balancing efficacy with
      tolerability and all the other patient-related variables that may affect
      treatment effectiveness beyond its efficacy. 

PMID- 24099149
TI  - Structure-activity-relationship studies around the 2-amino group and pyridine
      core of antimalarial 3,5-diarylaminopyridines lead to a novel series of pyrazine
      analogues with oral in vivo activity.
AB  - Replacement of the pyridine core of antimalarial 3,5-diaryl-2-aminopyridines led
      to the identification of a novel series of pyrazine analogues with potent oral
      antimalarial activity. However, other changes to the pyridine core and
      replacement or substitution of the 2-amino group led to loss of antimalarial
      activity. The 3,5-diaryl-2-aminopyrazine series showed impressive in vitro
      antiplasmodial activity against the K1 (multidrug resistant) and NF54 (sensitive)
      strains of Plasmodium falciparum in the nanomolar IC50 range of 6-94 nM while
      also demonstrating good in vitro metabolic stability in human liver microsomes.
      In the Plasmodium berghei mouse model, this series generally exhibited good
      efficacy at low oral doses. One of the frontrunner compounds, 4, displayed potent
      in vitro antiplasmodial activity with IC50 values of 8.4 and 10 nM against the K1
      and NF54 strains, respectively. When evaluated in P. berghei -infected mice,
      compound 4 was completely curative at an oral dose of 4 * 10 mg/kg. 

PMID- 24099151
TI  - Convenient synthesis of a highly soluble and stable phosphorescent platinum
      porphyrin dye.
AB  - A new highly soluble platinum porphyrin derivative 10 with suppressed
      photobleaching is prepared on a multigram scale from inexpensive starting
      materials. 10 possesses intense absorption bands at lambda = 463 nm (log epsilon
      = 5.39) and 633 nm (log epsilon = 5.20) with near-IR emission at 755 nm.
      Efficient NIR phosphorescence (PLQY = 0.45) and a large Stokes shift (eliminating
      self-absorption) make it an attractive and readily available material for a
      number of applications. 

PMID- 24099150
TI  - Epidemiology and clinical features of rotavirus and norovirus infection among
      children in Ji'nan, China.
AB  - BACKGROUND: Acute gastroenteritis caused by bacteria, virus and parasite is an
      important cause of childhood morbidity and mortality in developing countries.
      Rotavirus and norovirus have been recognized as the most common pathogens causing
      acute gastroenteritis among children. However, there is still no valuable data
      about infections of rotavirus and norovirus in children in Ji'nan, an eastern
      city in China. The aims of the present study are to determine the incidence of
      rotavirus and norovirus associated acute gastroenteritis in Ji'nan among
      children, to characterize rotavirus and norovirus strains circulating during this
      period; and to provide useful epidemiological and clinical data. METHODS: Fecal
      specimens and clinical data were collected from 767 children (502 outpatients and
      265 inpatients) under 5 years of age with acute diarrhea at Shandong University
      Qilu Hospital and Qilu children's Hospital in Ji'nan, China between February 2011
      and January 2012. Virus RNA was extracted, amplified, electrophoresed, sequenced
      and phylogenetically analyzed to determine the prevalent genotypes. Chi-square
      and U test were used to compare characteristics of clinical manifestation in each
      group. RESULTS: Of the 767 specimens 263 (34.3%) were positive for rotavirus and
      80 (10.4%) were positive for norovirus. Among 263 rotavirus positive cases, G3
      (40.7%) was the most prevalent serotype, P[8] (46.8%) was the dominant genotype
      and G3P[8] (31.9%) was the most common combination. All of the norovirus strains
      belonged to GII genogroup including GII.3, GII.4 and GII.6, of which GII.4
      (61.2%) was the predominant genotype. Phylogenetic analysis of the GII.4
      sequences showed that 18 GII.4 strains belonged to GII.4 2004-2006 cluster and 31
      GII.4 strains were divided into GII.4 2006b cluster. A peak number of rotavirus
      infections was observed during the cold season from November to next January.
      Higher rates of norovirus infections were detected from September to November.
      Most patients with rotavirus and norovirus associated diarrhea experienced
      vomiting (88.2% and 67.5%, respectively) and fever (79.1% and 46.3%,
      respectively). CONCLUSIONS: The present study showed that rotavirus and norovirus
      were still the important causative agents of pediatric diarrhea in Ji'nan during
      this period.

PMID- 24099153
TI  - The role of AFB microscopy training in improving the performance of laboratory
      professionals: analysis of pre and post training evaluation scores.
AB  - BACKGROUND: Tuberculosis (TB) remains major cause of morbidity and mortality due
      to any one of infectious agent worldwide. In low income countries, Ziehl-Neelsen
      sputum smear microscopy is the only cost-effective tool for diagnosis and
      monitoring of patients on treatment. In order to have efficient AFB microscopy
      centers, it is imperative to have continuous refresher training for laboratory
      professionals and strong External Quality Assessment (EQA) system). However, very
      little data exists as to the effect of in-service training on performance of
      laboratory personnel in Ethiopia.The objective of this study was to investigate
      the role of AFB microscopy refresher training on the performance of laboratory
      professionals. METHODS: A cross-sectional retrospective study was conducted to
      appraise theoretical and practical performance of laboratory professionals before
      and after AFB microscopy training. Theoretical assessment was based on standard
      questions while practical assessment was based on smear reading of 10 standard
      slides. Data on eight rounds of a five days training at Adama regional laboratory
      on AFB microscopy in 2009 was obtained and analyzed using SPSS 16.0 statistical
      software. RESULT: The pre-training mean score of the theoretical knowledge and
      practical skills were 61.8% and 75.7%, respectively. The post training mean
      scores were 84.2% and 89.2% for theoretical knowledge and practical skills,
      respectively. The increase in mean score of both theoretical and practical
      assessment was statistically significant (p < 0.0001). Post training mean score
      of theoretical knowledge was higher among diploma holders trainees than the BSc
      degree counter parts (p = 0.001). The mean scores on practice before and after
      training was dependent on participation in previous AFB microscopy trainings (p <
      0.0001). Proportions of trainees with both major and minor errors were found to
      decrease after they were trained. Trainees who have had previous training were
      found to commit less errors than those who were not participated in previous
      training (p < 0.0001). CONCLUSION: Training has improved theoretical and
      practical performance of laboratory professionals. Pre-placement and continuous
      training irrespective of lab professionals qualification and service year and
      sustainable EQA are highly recommended to ensure quality of AFB microscopy
      service.

PMID- 24099152
TI  - Effects of sympatholytic therapy on postmenopausal symptoms in hypertensive
      postmenopausal women.
AB  - OBJECTIVE: The short-term effects of two sympatholytic antihypertensive drug
      treatments, beta-blocking agent atenolol and imidazoline receptor-1 agonist
      moxonidine, on postmenopausal symptoms and their relationship to antihypertensive
      and insulin sensitivity effect were studied. DESIGN: This was a double-blind,
      prospectively randomized study in a multicenter, multinational setting in 112
      hypertensive, overweight, postmenopausal women without hormone therapy. METHODS:
      Treatment was either with moxonidine, 0.6 mg/day, or with atenolol, 50 mg/day,
      for 8 weeks. The main outcome measures were blood pressure, insulin sensitivity
      by Matsuda sensitivity index and postmenopausal symptoms (hot flushes,
      palpitations, insomnia, irritability, depression and general impression of the
      symptoms (GIS) through a questionnaire. RESULTS: Both atenolol and moxonidine
      caused a significant reduction in diastolic blood pressure of 9.5 mmHg and 6.2
      mmHg, respectively. The severity of hot flushes and palpitations were reduced
      significantly in both treatment groups. Relief from hot flushes was recorded in
      43% of women taking atenolol and in 27% (not significant between the groups) of
      moxonidine-treated patients. Palpitations were relieved in 41% and 25% (not
      significant between the groups) of the women in the atenolol- and moxonidine
      treated groups, respectively. In the atenolol group, insomnia and GIS were
      reduced significantly, with relief of symptoms occurring in 33% and 27% of the
      patients. A change in irritability was seen in blood pressure responders during
      the treatment in the atenolol group. There was no correlation between improvement
      of insulin sensitivity and relief of postmenopausal symptoms. CONCLUSIONS: In
      this study, two sympatholytic antihypertensives, atenolol and moxonidine,
      provided relief from hot flushes and palpitations, and atenolol additionally
      helped with insomnia and improved GIS.

PMID- 24099154
TI  - Determination of alpha-tocopherol in vegetable oils using a molecularly imprinted
      polymers-surface-enhanced Raman spectroscopic biosensor.
AB  - We report the development of a novel hybrid "capture-detection" molecularly
      imprinted polymers-surface-enhanced Raman spectroscopic (MIPs-SERS) biosensor for
      the detection and quantification of alpha-tocopherol (alpha-Toc) in vegetable
      oils. alpha-Toc served as the template for MIPs synthesis. Methacrylic acid
      formed as the functional monomer. Ethylene glycol dimethacrylate was the cross
      linking agent, and 2,2'-azobisisobutyronitrile was used as the initiator. The
      synthesized MIPs functioned to rapidly and selectively adsorb and separate alpha
      Toc from oil components. We validated a dendritic silver nanostructure
      synthesized by a displacement reaction to be a suitable SERS substrate for the
      enhancement of Raman signals. Second-derivative transformations and chemometric
      models based upon SERS spectral features confirmed the possibility of a rapid and
      precise detection and quantification of different spiking levels of alpha-Toc in
      four different sources of vegetable oils (Mahalanobis distance from 15.93 to
      34.01 for PCA model; R > 0.92, RMSE < 0.41 for PLSR model). The MIPs-SERS
      biosensor had a high sensitivity as well as a good recovery for alpha-Toc
      analysis in vegetable oils. The entire analysis required 15 min or less to
      complete with limited sample preparation. 

PMID- 24099155
TI  - New insights into the role of glycogen synthase kinase-3 in Alzheimer's disease.
AB  - INTRODUCTION: Glycogen synthase kinase-3 (GSK-3) is recognized as a crucial
      player in many cellular functions and its activity is tightly controlled by
      complex mechanisms that are each dependent upon specific signaling pathways.
      Furthermore, GSK-3 dysfunction has been linked to a number of pathologies,
      including Alzheimer's disease (AD). In particular, the involvement of GSK-3 in
      several key pathophysiological pathways leading to AD and neurodegenerative
      diseases has placed this enzyme in a central position in this disorder. AREAS
      COVERED: This article offers a review of the relationship between GSK-3 and AD
      with a special focus on recent evidence showing a key role of GSK-3 activity in
      modulating cellular pathways controlling amyloid formation, especially through
      the control of beta-site APP-cleaving enzyme 1 gene expression, as well as its
      role as a key regulator of neurogenesis. EXPERT OPINION: GSK-3 appears to be a
      cellular nexus, integrating several signaling systems, including several second
      messengers and a wide selection of cellular stimulants. The next few years will
      certainly bring us further insights into the cellular functions of this
      fascinating enzyme and its potential as a therapeutic target in AD and other
      neurological disorders.

PMID- 24099157
TI  - The influence of workplace injuries on work-family conflict: job and financial
      insecurity as mechanisms.
AB  - Research examining the outcomes of workplace injuries has focused on high costs
      to the organization. In this study, we utilize conservation of resources theory
      to develop and test a model that explains how and under what circumstances
      workplace injuries impact employees' perceptions of how their work interferes
      with their family. Results from 194 registered nurses (along with 85 of their
      spouses), using path analytic tests of moderated mediation, provide support for
      the prediction that the mediated effect of workplace injury severity on work
      family conflict (through job and financial insecurity) is weaker when employees
      perceive high levels of supervisor support. We discuss the implications of these
      findings for the study of job and financial insecurity and work-family conflict.
      Limitations of this study and directions for future research are also presented.

PMID- 24099158
TI  - Work-school conflict and health outcomes: beneficial resources for working
      college students.
AB  - This study extends prior college student employment research by examining health
      as an outcome variable. Using 2-wave data from a sample of 216 student workers,
      this study examined work-school conflict as a predictor of psychological and
      physical health among working college students. Additionally, 3 resource
      providing variables--work-school facilitation, supervisor work-school support,
      and personal fulfillment at work--were tested for buffering effects in the
      relation between work-school conflict and health. Results demonstrated that work
      school conflict was a significant predictor of psychological health but not
      physical health. All 3 resource-providing variables ameliorated the negative
      relation between work-school conflict and psychological health, whereas only
      personal fulfillment weakened the positive relation between work-school conflict
      and physical symptoms. These findings suggest the benefits of work-school
      facilitation, supervisor work-school support, and personal fulfillment in
      minimizing the detrimental effects of work-school conflict on health outcomes.
      Theoretical and practical implications for researchers, educational institutions,
      and organizations are discussed.

PMID- 24099156
TI  - Transcriptional regulation by hypoxia inducible factors.
AB  - The cellular response to oxygen deprivation is governed largely by a family of
      transcription factors known as Hypoxia Inducible Factors (HIFs). This review
      focuses on the molecular mechanisms by which HIFs regulate the transcriptional
      apparatus to enable the cellular and organismal response to hypoxia. We discuss
      here how the various HIF polypeptides, their posttranslational modifications,
      binding partners and transcriptional cofactors affect RNA polymerase II activity
      to drive context-dependent transcriptional programs during hypoxia.

PMID- 24099159
TI  - Living up to safety values in health care: the effect of leader behavioral
      integrity on occupational safety.
AB  - While previous research has identified that leaders' safety expectations and
      safety actions are important in fostering occupational safety, research has yet
      to demonstrate the importance of leader alignment between safety expectations and
      actions for improving occupational safety. We build on safety climate literature
      and theory on behavioral integrity to better understand the relationship between
      the leader's behavioral integrity regarding safety and work-related injuries. In
      a time-lagged study of 658 nurses, we find that behavioral integrity for high
      safety values is positively associated with greater reporting of fewer and less
      severe occupational injuries. The effects of behavioral integrity regarding
      safety can be better understood through the mediating mechanisms of safety
      compliance and psychological safety toward one's supervisor. We discuss the
      implications of our findings for future research on safety climate.

PMID- 24099160
TI  - Unhealthy and present: motives and consequences of the act of presenteeism among
      Taiwanese employees.
AB  - The aim of this study was twofold: first, to delineate the underlying motives of
      the act of presenteeism and develop suitable measures for both the motives and
      the behavioral manifestation of the act; second, to systematically examine work
      and health consequences of the act of presenteeism in a Chinese work context.
      Using structured questionnaires, we employed a 2-wave panel study design in which
      antecedents, motives, and consequences of the act of presenteeism were measured
      in a diverse sample of 245 full-time Chinese employees in Taiwan. Hierarchical
      regression analyses showed that self-efficacy and neuroticism were significantly
      associated with approach and avoidance motives for the act of presenteeism,
      respectively. Moreover, analyzing the panel data with fixed effects
      specifications, we found that the act of presenteeism was negatively associated
      with employees' physical health, mental health, and job satisfaction, whereas it
      was positively associated with exhaustion. In conclusion, the present study shed
      some light on motives, behavioral manifestations, antecedents, and consequences
      of the act of presenteeism to extend the existing literature.

PMID- 24099161
TI  - Differentiation between work and nonwork self-aspects as a predictor of
      presenteeism and engagement: cross-cultural differences.
AB  - Research on the work-life interface does not specifically account for how
      individuals cognitively conceptualize their work and nonwork lives in terms of
      the differentiation between work and nonwork self-aspects. In addition, no cross
      cultural research examines self-concept differentiation in conjunction with
      employee outcomes of presenteeism and engagement, pointing to a need to study
      these relationships cross-culturally. Results of the current study revealed
      cultural differences in self-concept differentiation, engagement, mental
      presenteeism, and physical presenteeism. Indian participants reported lower
      levels of differentiation and higher levels of engagement, mental presenteeism,
      and physical presenteeism than American participants. Nationality interacted with
      self-concept differentiation to predict mental presenteeism, physical
      presenteeism, and engagement. Among Indian participants, self-concept
      differentiation did not impact scores on the other variables. However, among
      American participants, those lower in differentiation reported greater
      engagement, lower mental presenteeism, and lower physical presenteeism. These
      results have important implications for the study of the work-life interface, and
      they provide evidence that engagement and presenteeism may be culturally
      contingent.

PMID- 24099162
TI  - It's self defense: how perceived discrimination promotes employee withdrawal.
AB  - Integrating theory on stress, stigma, and coping, the present study sheds light
      on how employees react to perceived discrimination (PD) in the workplace. Using
      three national samples, we found that PD based on race, sex, age, family
      obligation, and sexual orientation related to physical withdrawal (i.e.,
      lateness, absenteeism,and intent to quit) indirectly through psychological
      withdrawal (i.e., burnout and engagement) such that PD corresponded in less
      engagement and more burnout, which related to increased lateness, absenteeism,
      and intent to quit [corrected].Further, these indirect relationships were
      moderated by employees' coping mechanisms with those who were more apt to change
      the situation or to avoid the stressor exhibiting weaker relationships between PD
      and psychological withdrawal. Though each of these studies is cross-sectional in
      nature and therefore cannot provide strong evidence of causal ordering of the
      variables in our model, the replication and extension of results over three
      databases and multiple forms of discrimination, coping, psychological, and
      physical withdrawal demonstrates that understanding the relationships explored in
      these studies can aid researchers and practitioners in enhancing employee quality
      of life and productivity.

PMID- 24099164
TI  - Opposites attract or attack? The moderating role of diversity climate in the team
      diversity-interpersonal aggression relationship.
AB  - This study embraced a unit-level diversity perspective to examine interpersonal
      aggression, as experienced or witnessed by individual team members. Specifically,
      our aim was to explore the moderating role of a unit's diversity climate in the
      link between unit-level surface diversity in terms of ethnicity, sex, age, and
      tenure, and individual-level perceptions of interpersonal aggression. We tested
      our hypotheses with 30 nursing units using the Mixed-Linear Model procedure
      appropriate for nested samples. Results demonstrated that diversity climate
      moderated the relationships between tenure and ethnic unit diversity and
      interpersonal aggression, experienced or witnessed among individual team members.
      Moreover, regardless of the level of diversity climate, age diversity was
      positively linked to interpersonal aggression, whereas sex diversity was
      negatively linked to it. These findings imply that the unit's context affects
      interpersonal aggression and provides important theoretical and practical
      implications to proactively prevent interpersonal aggression.

PMID- 24099165
TI  - Does work stress make you shorter? An ambulatory field study of daily work
      stressors, job control, and spinal shrinkage.
AB  - Body height decreases throughout the day due to fluid loss from the
      intervertebral disk. This study investigated whether spinal shrinkage was greater
      during workdays compared with nonwork days, whether daily work stressors were
      positively related to spinal shrinkage, and whether job control was negatively
      related to spinal shrinkage. In a consecutive 2-week ambulatory field study,
      including 39 office employees and 512 days of observation, spinal shrinkage was
      measured by a stadiometer, and calculated as body height in the morning minus
      body height in the evening. Physical activity was monitored throughout the 14
      days by accelerometry. Daily work stressors, daily job control, biomechanical
      workload, and recreational activities after work were measured with daily
      surveys. Multilevel regression analyses showed that spinal disks shrank more
      during workdays than during nonwork days. After adjustment for sex, age, body
      weight, smoking status, biomechanical work strain, and time spent on physical and
      low-effort activities during the day, lower levels of daily job control
      significantly predicted increased spinal shrinkage. Findings add to knowledge on
      how work redesign that increases job control may possibly contribute to
      preserving intervertebral disk function and preventing occupational back pain.

PMID- 24099166
TI  - Do nurses who work in a fair organization sleep and perform better and why?
      Testing potential psychosocial mediators of organizational justice.
AB  - We examined whether organizational justice is associated with sleep quality and
      performance in a population-based sample of 1,729 Finnish registered nurses
      working full time. In addition, we tested psychological mechanisms mediating the
      potential association. The results of multivariate linear regression analyses
      showed higher organizational justice to be associated with fewer sleeping
      problems (beta values range from -.20 to -.11) and higher self-reported
      performance (beta values range from .05 to .35). Furthermore, psychological
      distress (related to the psychological stress model) and job involvement (related
      to the psychosocial resource model) mediated the association between
      organizational justice and sleep. Sleeping problems partly mediated the
      association between organizational justice and performance. Psychological
      distress explained 51% to 83% and job involvement explained 10% to 15% of the
      total effects of justice variables on sleeping problems. The findings provide
      support for the psychological stress model and offer practical implications for
      reducing nurses' sleeping problems.

PMID- 24099167
TI  - Associations between five-factor model traits and perceived job strain: a
      population-based study.
AB  - This study examined the association between Five-Factor Model personality traits
      and perceived job strain. The sample consisted of 758 women and 614 men (aged 30
      45 years in 2007) participating in the Young Finns study. Personality was
      assessed with the Neuroticism, Extraversion, Openness, Five-Factor Inventory (NEO
      FFI) questionnaire and work stress according to Karasek's demand-control model of
      job strain. The associations between personality traits and job strain and its
      components were measured by linear regression analyses where the traits were
      first entered individually and then simultaneously. The results for the
      associations between individually entered personality traits showed that high
      neuroticism, low extraversion, low openness, low conscientiousness, and low
      agreeableness were associated with high job strain. High neuroticism, high
      openness, and low agreeableness were related to high demands, whereas high
      neuroticism, low extraversion, low openness, low conscientiousness, and low
      agreeableness were associated with low control. In the analyses for the
      simultaneously entered traits, high neuroticism, low openness, and low
      conscientiousness were associated with high job strain. In addition, high
      neuroticism was related to high demands and low control, whereas low extraversion
      was related to low demands and low control. Low openness and low
      conscientiousness were also related to low control. This study suggests that
      personality is related to perceived job strain. Perceptions of work stressors and
      decision latitude are not only indicators of structural aspects of work but also
      indicate that there are individual differences in how individuals experience
      their work environment.

PMID- 24099169
TI  - Growth profile of Carboxydothermus hydrogenoformans on pyruvate.
AB  - Carboxydothermus hydrogenoformans is a thermophilic anaerobic strain most widely
      known for its ability to produce hydrogen (H2) when grown on carbon monoxide
      (CO). Although relatively well studied, growth characterization on pyruvate has
      never been assessed. The present work fully characterizes growth of the bacterium
      on pyruvate as a sole carbon source. C. hydrogenoformans demonstrated a growth
      rate of 0.03 h-1, with pyruvate consumption ranging between 0.21 and 0.48 mol . g
      1 volatile suspended solid . d-1. A lag phase was also observed when switching
      from pyruvate to CO. When grown simultaneously on pyruvate and CO, pyruvate
      consumption was initiated upon CO depletion. This was attributed to pyruvate
      oxidation inhibition by CO, and not to a diauxic phenomenom. The strain also
      showed homoacetogenic activity. 

PMID- 24099170
TI  - Measuring the plasticity of developmental rate across insect populations: comment
      on Rocha and Klaczko (2012).
AB  - Rocha and Klaczko emphasize the general complexity of reaction norm shape and
      caution that ignoring such complexity can be misleading when forcing nonlinear
      reaction norms into linear shapes. They refer to our article on differences in
      plasticity of Drosophila serrata populations along a latitudinal gradient as an
      example of a misleading simplifying approach. However, their claim that an
      artifact is introduced into our analyses by calculating developmental rate as the
      reciprocal of development time (rate = time(-1)) is based on a misunderstanding
      of the mathematical properties of the thermal developmental rate reaction norm.
      Here we discuss why developmental rate is a suitable measure for our study and
      under which circumstances it is appropriate to describe developmental rate by a
      linear model.

PMID- 24099171
TI  - Halide ions effects on surface excess of long chain ionic liquids water
      solutions.
AB  - The interfacial structure and composition of water solutions with
      alkylimidazolium ionic liquids varying in their halide anions ([C12mim][X], X =
      Cl and I) were investigated by X-ray near-total-reflection fluorescence
      spectroscopy and X-ray reflectivity measurements. We demonstrate that X-ray
      fluorescence and reflectivity techniques provide a more direct measurement of
      surface adsorption. Furthermore, we show that for [C12mim][Cl] and [C12mim][I]
      solutions with mixed inorganic salts (NaI, NaCl), I(-) ions replace Cl(-) above
      the critical micelle concentration (CMC) of [C12mim][Cl] at much lower
      concentrations of NaI, whereas NaCl concentrations a hundred times higher than
      the CMC of [C12mim][I] only partially replace the I(-) at the interface. Our
      surface-sensitive X-ray diffraction and spectroscopy provide two independent
      tools to directly determine the surface adsorption of ionic surfactants and the
      interfacial composition of the surface films. 

PMID- 24099172
TI  - The ORCA2 transcription factor plays a key role in regulation of the terpenoid
      indole alkaloid pathway.
AB  - BACKGROUND: The terpenoid indole alkaloid (TIA) pathway leads to the production
      of pharmaceutically important drugs, such as the anticancer compounds vinblastine
      and vincristine. Unfortunately, these drugs are produced in trace amounts,
      causing them to be very costly. To increase production of these drugs, an
      improved understanding of the TIA regulatory pathway is needed. Towards this end,
      transgenic Catharanthus roseus hairy roots that overexpress the ORCA2 TIA
      transcriptional activator were generated and characterized. RESULTS:
      Transcriptional profiling experiments revealed that overexpression of ORCA2
      results in altered expression of key genes from the indole and terpenoid
      pathways, which produce precursors for the TIA pathway, and from the TIA pathway
      itself. In addition, metabolite-profiling experiments revealed that
      overexpression of ORCA2 significantly affects the levels of several TIA
      metabolites. ORCA2 overexpression also causes significant increases in transcript
      levels of several TIA regulators, including TIA transcriptional repressors.
      CONCLUSIONS: Results presented here indicate that ORCA2 plays a critical role in
      regulation of TIA metabolism. ORCA2 regulates expression of key genes from both
      feeder pathways, as well as the genes (STR and SGD) encoding the enzymes that
      catalyze the first two steps in TIA biosynthesis. ORCA2 may play an especially
      important role in regulation of the downstream branches of the TIA pathway, as it
      regulates four out of five genes characterized from this part of the pathway.
      Regulation of TIA transcriptional repressors by ORCA2 may provide a mechanism
      whereby increases in TIA metabolite levels in response to external stimuli are
      transient and limited in magnitude.

PMID- 24099173
TI  - Vitamin D analog EB1089 induces apoptosis in a subpopulation of SGC-7901 gastric
      cancer cells through a mitochondrial-dependent apoptotic pathway.
AB  - Gastric cancer is the second leading cause of cancer death worldwide. Cancer stem
      like side population (SP) cells may be important factors that hinder efficacy of
      chemopreventative and chemotherapeutic approaches in gastric cancer. EB1089 is an
      antitumor agent that has been used in many cancers; however, no reports to date
      have determined the effects of EB1089 in gastric cancer. In our study, SP and
      main population (MP) cells were isolated from 4 gastric cancer cell lines in
      different stages of differentiation by flow cytometry (FCM) and confirmed by
      reverse transcription polymerase chain reaction (RT-PCR) and Western blot. EB1089
      decreased the proliferation, increased apoptosis, and induced mitochondrial
      damage in the SP cells isolated from 1 cell type (SGC-7901), but not MP cells,
      through increased Bax and decreased Bcl-2 and Bcl-xL protein expression. This
      protein expression pattern induced the activation of caspase-3 and caspase-9. The
      effects of EB1089 on SGC-7901 SP cells were blocked by treating cells with
      vitamin D receceptor (VDR) siRNA or butin (an inhibitor of the mitochondrial
      apoptosis pathway). Our results suggest that EB1089 targets SGC-7901 SP cells
      through a mitochondrial apoptosis pathway. However, further studies are needed to
      elucidate the signal transduction between VDR and the mitochondrial apoptosis
      pathway. 

PMID- 24099174
TI  - beta-Lactoglobulin improves liposome's encapsulation properties for vitamin E
      delivery.
AB  - Vitamin E (VE) or alpha-tocopherol is the major fat-soluble antioxidant in the
      human body. It is a sensitive, easily oxidized in the air, molecule, so it must
      be protected from pro-oxidant elements which could affect its physiological
      benefits. Encapsulation constitutes a promising approach to maintain VE native
      properties over time and increase its concentration in aqueous media. Liposomes
      have been studied as sustained delivery systems, being biodegradable, non-toxic
      and non-immunogenic. A new liposome/beta-lactoglobulin (beta-Lg) formulation has
      been developed and characterized as a possible stable delivery system for VE.
      beta-Lg has been selected due to its property to bind a variety of hydrophobic
      molecules. The aim of this study was the preparation of beta-Lg-liposome
      formulation and the determination of VE encapsulation efficiency, in order to
      develop a new more efficient carrier for VE in aqueous media.

PMID- 24099175
TI  - Preliminary evidence of equivalence of alternate forms of the ImPACT.
AB  - The ImPACT (Immediate Postconcussion Assessment and Cognitive Testing) is a
      computerized neurocognitive test used to assist in the management of sport
      concussion management. A number of studies have documented the reliability and
      sensitivity of the ImPACT, but no studies have examined the equivalence of the
      ImPACT's alternate forms. The objective of our study was to determine the
      equivalence of the ImPACT's five alternate forms. Participants were administered
      alternate forms of ImPACT based on clinically relevant time frame derived from an
      extensive sports concussion database. Participants completed a baseline
      assessment followed by various combinations of the remaining alternate forms at
      45 and 50 days. Inferential Confidence Intervals were calculated for each
      composite score for all alternate forms. We found non-equivalence between ImPACT
      form 1 and forms 2, 3, and 4 on the Verbal Memory and between forms 2 and 4.
      ImPACT forms 1 and 3 were not equivalent on the Visual Memory Composite. Finally,
      ImPACT forms 3 and 4 were not equivalent on the Visual Motor Speed and Reaction
      Time Composites. Alternate form equivalence is necessary to minimize measurement
      error and optimize clinical decision making. Clinicians using the ImPACT should
      consider non-equivalence of some forms on certain Composites when interpreting
      ImPACT following sports concussion. 

PMID- 24099176
TI  - Validation of the French version of the Amsterdam preoperative anxiety and
      information scale (APAIS).
AB  - BACKGROUND: Most patients are anxious before surgery. The level of preoperative
      anxiety depends on several factors and merits an objective evaluation. The
      Amsterdam Preoperative Anxiety and Information Scale (APAIS) is a self-report
      questionnaire comprising six questions that have been developed and validated to
      evaluate the preoperative anxiety of patients. This global index assesses three
      separate areas: anxiety about anaesthesia, anxiety about surgery, and the desire
      for information. The purpose of this study was to translate the APAIS into French
      and to evaluate the psychometric properties of the French version of the APAIS.
      METHODS: The process consisted of two steps. The first step involved the
      production of a French version of the APAIS that was semantically equivalent to
      the original version. In the second step, we evaluated the psychometric
      properties of the French version, including the internal consistency and
      reliability, the differential item functioning, and the external validity.
      Participants older than 18, undergoing elective surgery (except obstetric), able
      to understand and read French, and able to complete a self-report questionnaire
      were eligible for inclusion in the study. A forward-backward translation was
      performed. The psychometric evaluation covered three domains: internal validity,
      external validity, and acceptability. Within 4-48 h after surgery, the patients
      were asked to complete the "Evaluation du Vecu de l'ANesthesie" questionnaire"
      (EVAN) questionnaire, which is a validated, multi-dimensional questionnaire that
      assesses the patient's experiences in the perioperative period. RESULTS: A
      database with 175 patients was created. The principal component factor analysis
      revealed the same three-dimensional structure as the original scale. The
      confirmatory factor analysis showed a strong fit with a root mean square error of
      approximation of 0.069 and a comparative fit index of 1.00. The amount of
      differential item functioning (DIF) between the subgroups of patients (i.e.,
      based on age, gender, type of anaesthesia or surgery, premedication, ASA physical
      status, and ambulatory course) was low. The APAIS was strongly correlated with
      the dimensions of the EVAN. Each dimension had a low proportion of missing values
      (ranging from 0.6 to 2.9%), which indicates good acceptability of the
      questionnaire. CONCLUSIONS: The French version of the APAIS is valid and
      reliable. The availability of this tool enables the evaluation of anxiety in
      French patients undergoing anaesthesia.

PMID- 24099177
TI  - Family planning counseling for women living with HIV: a systematic review of the
      evidence of effectiveness on contraceptive uptake and pregnancy incidence, 1990
      to 2011.
AB  - BACKGROUND: Family planning is an important public health intervention with
      numerous potential health benefits for all women. One of those key benefits is
      the prevention of mother-to-child transmission of HIV, through the prevention of
      unintended pregnancies among women living with HIV. METHODS: We conducted a
      systematic review of the effectiveness of family planning counseling
      interventions for HIV infected women in low- and middle-income countries.
      RESULTS: We found nine articles which met the inclusion criteria for this review,
      all from Africa. Though these studies varied in the specifics of the
      interventions provided, research designs and measures of outcomes, key features
      were discernible. Providing concerted information and support for family planning
      use, coupled with ready access to a wide range of contraceptive methods, seemed
      most effective in increasing use. Effects on pregnancy overall were difficult to
      measure, however: no studies assessed the effect on unintended pregnancy.
      CONCLUSIONS: Though these results are far from definitive, they do highlight the
      need for strengthened efforts to integrate family planning counseling and access
      to services into HIV prevention, and for greater consistency of effort over time.
      Studies which specifically investigate fertility intentions and desires of women
      living with HIV, contraception use following interventions to increase knowledge,
      awareness, motivation and access to the means to act on those intentions and
      unintended pregnancies would be valuable to help clinic personnel, programme
      planners and policy makers guide the development of the integrated services they
      offer.

PMID- 24099178
TI  - Evaluation of 111In-labeled EPep and FibPep as tracers for fibrin SPECT imaging.
AB  - Fibrin targeting is an attractive strategy for nuclear imaging of thrombosis,
      atherosclerosis and cancer. Recently, FibPep, an (111)In-labeled fibrin-binding
      peptide, was established as a tracer for fibrin SPECT imaging and was reported to
      allow sensitive detection of minute thrombi in mice using SPECT. In this study,
      we developed EPep, a novel (111)In-labeled fibrin-binding peptide containing the
      fibrin-binding domain of the clinically verified EP-2104R peptide, and sought to
      compare the potential of EPep and FibPep as tracers for fibrin SPECT imaging. In
      vitro, both EPep and FibPep showed high stability in serum, but were less stable
      in liver and kidney homogenate assays. Both peptide probes displayed comparable
      affinities toward human and mouse derived fibrin (Kd ~ 1 MUM), and similarly to
      FibPep, EPep showed fast blood clearance, low nontarget uptake and high thrombus
      uptake (6.8 +/- 1.2% ID g(-1)) in a mouse carotid artery thrombosis model.
      Furthermore, EPep showed a similar affinity toward rat derived fibrin (Kd ~ 1
      MUM), displayed high thrombus uptake in a rat carotid artery thrombosis model
      (0.74 +/- 0.39% ID g(-1)), and allowed sensitive detection of thrombosis in rats
      using SPECT. In contrast, FibPep displayed a significantly lower affinity toward
      rat derived fibrin (Kd ~ 14 MUM) and low uptake in rat thrombi (0.06 +/- 0.02% ID
      g(-1)) and did not allow clear visualization of carotid artery thrombosis in rats
      using SPECT. These results were confirmed ex vivo by autoradiography, which
      showed a 7-fold higher ratio of activity in the thrombus over the contralateral
      carotid artery for EPep in comparison to FibPep. These findings suggest that the
      FibPep binding fibrin epitope is not fully homologous between humans and rats,
      and that preclinical rat models of disease should not be employed to gauge the
      clinical potential of FibPep. In conclusion, both peptides showed approximately
      similar metabolic stability and affinity toward human and mouse derived fibrin,
      and displayed high thrombus uptake in a mouse carotid artery thrombosis model.
      Therefore, both EPep and FibPep are promising fibrin targeted tracers for
      translation into clinical settings to serve as novel tools for molecular imaging
      of fibrin. 

PMID- 24099179
TI  - NaviCell: a web-based environment for navigation, curation and maintenance of
      large molecular interaction maps.
AB  - BACKGROUND: Molecular biology knowledge can be formalized and systematically
      represented in a computer-readable form as a comprehensive map of molecular
      interactions. There exist an increasing number of maps of molecular interactions
      containing detailed and step-wise description of various cell mechanisms. It is
      difficult to explore these large maps, to organize discussion of their content
      and to maintain them. Several efforts were recently made to combine these
      capabilities together in one environment, and NaviCell is one of them. RESULTS:
      NaviCell is a web-based environment for exploiting large maps of molecular
      interactions, created in CellDesigner, allowing their easy exploration, curation
      and maintenance. It is characterized by a combination of three essential
      features: (1) efficient map browsing based on Google Maps; (2) semantic zooming
      for viewing different levels of details or of abstraction of the map and (3)
      integrated web-based blog for collecting community feedback. NaviCell can be
      easily used by experts in the field of molecular biology for studying molecular
      entities of interest in the context of signaling pathways and crosstalk between
      pathways within a global signaling network. NaviCell allows both exploration of
      detailed molecular mechanisms represented on the map and a more abstract view of
      the map up to a top-level modular representation. NaviCell greatly facilitates
      curation, maintenance and updating the comprehensive maps of molecular
      interactions in an interactive and user-friendly fashion due to an imbedded
      blogging system. CONCLUSIONS: NaviCell provides user-friendly exploration of
      large-scale maps of molecular interactions, thanks to Google Maps and WordPress
      interfaces, with which many users are already familiar. Semantic zooming which is
      used for navigating geographical maps is adopted for molecular maps in NaviCell,
      making any level of visualization readable. In addition, NaviCell provides a
      framework for community-based curation of maps.

PMID- 24099180
TI  - Challenges of COPD diagnosis.
AB  - INTRODUCTION: Chronic obstructive pulmonary disease (COPD) is a leading cause of
      death worldwide and this burden is predicted to increase unless exposure to risk
      factors is addressed. Diagnosis of COPD is a challenge: COPD is underdiagnosed
      and frequently misdiagnosed for asthma or other respiratory conditions. Although
      spirometry is only one parameter for establishing a clinical diagnosis of COPD,
      lack of routine spirometry is a key cause of COPD misdiagnosis. Differential
      diagnosis from asthma is essential because the treatment strategies for, and
      progression and outcomes of, the two conditions vary greatly. AREAS COVERED: Here
      the authors review methods for the differential diagnosis of COPD and asthma;
      approaches to improve diagnosis, including case-finding and screening; the
      identification of specific COPD phenotypes and targeted therapy; and the
      potential role of exhaled biomarkers in the diagnosis of COPD. EXPERT OPINION:
      Methods to diagnose COPD, specifically differential diagnosis from asthma, have
      improved in recent years. To translate these into clinical practice will require
      the development of combined guidelines for COPD and asthma that include COPD
      asthma overlap syndrome and are based on evidence from randomized controlled
      trials.

PMID- 24099181
TI  - Ru(II)-catalyzed ortho-C-H amination of arenes and heteroarenes at room
      temperature.
AB  - The Ru(II)-catalyzed ortho-C-H amination directed by a weakly coordinating amide
      auxiliary with O-benzoyl hydroxylamines at room temperature has been achieved.
      This reaction is compatible with heterocycles including pyrazole, thiophene,
      benzothiophene, furan, benzofuran, and indole. 

PMID- 24099182
TI  - It's not unusual.

PMID- 24099183
TI  - WONCA inauguration speech 2013.

PMID- 24099184
TI  - Novel insights into the pathology of upper gut symptoms: new syndromes, new
      diseases.

PMID- 24099185
TI  - The tale of out-of-pocket spending on health care.

PMID- 24099188
TI  - Retaining our right to regulate alcohol warnings.

PMID- 24099189
TI  - The quality of Australian health journalism is important for public health.

PMID- 24099190
TI  - Surgery for adult obstructive sleep apnoea.
AB  - Surgery rarely cures OSA, but the lack of cure should not be judged as failure.
      New higher-level evidence shows excellent clinical outcomes with surgery, in long
      term health, short-term symptoms and quality of life, even when complete cure is
      not achieved. It is unrealistic and inappropriate to expect that surgery must
      result in a cure to be considered worthwhile. Evaluating surgical treatments is
      complicated because placebo control is usually not feasible with invasive
      therapies, randomisation to or away from invasive therapy may limit patient
      enrolment and generalisability, and surgery is a heterogeneous array of
      procedures and combinations of procedures. Despite these testing challenges, well
      controlled studies are showing important benefits of surgery and, moreover, of
      combinations of surgical procedures.

PMID- 24099191
TI  - Acute febrile respiratory infection symptoms in Australian Hajjis at risk of
      exposure to Middle East respiratory syndrome coronavirus.

PMID- 24099192
TI  - Sexual harassment of Australian female general practitioners by patients.

PMID- 24099193
TI  - Australia's dietary guidelines and the environmental impact of food "from paddock
      to plate".

PMID- 24099194
TI  - Australia's dietary guidelines and the environmental impact of food "from paddock
      to plate".

PMID- 24099195
TI  - Australia's dietary guidelines and the environmental impact of food "from paddock
      to plate".

PMID- 24099196
TI  - Australia's dietary guidelines and the environmental impact of food "from paddock
      to plate".

PMID- 24099197
TI  - Australia's dietary guidelines and the environmental impact of food "from paddock
      to plate".

PMID- 24099198
TI  - Salicylate elimination diets in children: is food restriction supported by the
      evidence?

PMID- 24099199
TI  - Salicylate elimination diets in children: is food restriction supported by the
      evidence?

PMID- 24099200
TI  - Salicylate elimination diets in children: is food restriction supported by the
      evidence?

PMID- 24099201
TI  - Trends in general practice services in two cohorts of Australian children between
      2003-2004 and 2010-2011.

PMID- 24099202
TI  - Emergence of Streptococcus pneumoniae serotype 15A after the introduction of the
      conjugate vaccine in Victoria.

PMID- 24099203
TI  - Utility of reports and routine correspondence from the National HPV Vaccination
      Program Register.

PMID- 24099204
TI  - Treatment outcomes for Indigenous and non-Indigenous inmates with hepatitis C in
      New South Wales prisons.

PMID- 24099205
TI  - The look of leptospirosis in Victoria - recent trends.

PMID- 24099206
TI  - Treatment failure in atopic dermatitis as a result of parental health belief.
AB  - The gold standard for treatment of atopic dermatitis is topical corticosteroids.
      Parental alternative health beliefs and fear of topical corticosteroids may lead
      to non-adherence and treatment failure. At the extreme end, such beliefs may
      result in neglect constituting reportable child maltreatment. We examine the
      legal repercussions of such abuse in the criminal case resulting from the death
      of Gloria Sam. 

PMID- 24099207
TI  - The economic evaluation of personalised oncology medicines: ethical challenges.
AB  - Insights into the molecular drivers of cancer are providing opportunities for the
      development of new targeted treatments and more personalised approaches to cancer
      management. Drugs targeting mutant epidermal growth factor receptors, such as
      erlotinib and gefitinib, may provide more effective, safer and better tolerated
      treatment options compared with chemotherapy among appropriately selected
      patients with advanced non-small cell lung cancer (NSCLC). First-line access to
      these newer treatments remains unfunded after several considerations by the
      Pharmaceutical Benefits Advisory Committee and their assessment that these are
      not cost-effective treatments. We suggest that there may be evidentiary and
      ethical challenges associated with the assessment of the cost-effectiveness of
      personalised oncology medicines in Australia, and that a new approach is needed
      to determine the value and cost-effectiveness of personalised medicine. 

PMID- 24099208
TI  - Can't escape it: the out-of-pocket cost of health care in Australia.
AB  - OBJECTIVE: To analyse the annual out-of-pocket (OOP) expenditure on health care
      as directly reported by Australian households grouped into older households
      (those with a reference person aged >= 65 years) and younger households (those
      with a reference person aged < 65 years). DESIGN: Descriptive analysis of
      statutory data collected by the Australian Bureau of Statistics. SETTING AND
      PARTICIPANTS: Probability sample of 9774 households across all states and
      territories. MAIN OUTCOME MEASURES: OOP expenditure on health care. RESULTS: The
      mean annual OOP expenditure on health care among the older households was
      estimated as $3585 +/- $686 (9.4% of the total expenditure on all goods and
      services), and among the younger households, it was $3377 +/- $83 (4.7% of the
      total expenditure on all goods and services). Cost of medicines (mainly non
      prescription drugs and to a lesser extent the copayments for Pharmaceutical
      Benefits Scheme scripts) was the biggest item of expenditure for the older
      households, and the cost of private health insurance (PHI) was the most expensive
      item for the younger households. Overall, the OOP expenditure, as reported by the
      Australian households, was $28.7 +/- $1.3 billion compared with $21.2 billion as
      reported by the Australian Institute of Health and Welfare. Unlike our estimate,
      the Institute's figure was based on statutory data collections and did not
      include the cost of PHI premiums. CONCLUSIONS: OOP expenses account for almost a
      quarter (22%) of the total health care costs in Australia. The mean annual OOP
      expenditure was slightly higher for the older households compared with the
      younger households, despite the fact that the older households had significantly
      lower income and had greater access to health care cards, which were used to
      defray additional health care costs associated with age.

PMID- 24099209
TI  - Sickness certification of workers compensation claimants by general practitioners
      in Victoria, 2003-2010.
AB  - OBJECTIVE: To examine patterns of the sickness certification of workers
      compensation claimants by general practitioners in Victoria, Australia, by nature
      of injury or illness. DESIGN, SETTING AND PATIENTS: Retrospective analysis of
      Victorian workers compensation data for all injured and ill workers with an
      accepted workers compensation claim between 2003 and 2010. MAIN OUTCOME MEASURES:
      Type (unfit for work, alternative duties, or fit for work) and duration of
      initial medical certificates relating to workers compensation claims that were
      issued by GPs, in six categories of injury and illness. RESULTS: Of 124,424
      initial medical certificates issued by GPs, 74.1% recommended that workers were
      unfit for work and 22.8% recommended alternative duties. Unfit-for-work
      certificates were issued to 94.1% of workers with mental health conditions, 81.3%
      of those with fractures, 79.1% of those with other traumatic injuries, 77.6% of
      those with back pain and strains, 68.0% of those with musculoskeletal conditions
      and 53.0% of those with other diseases. Alternative-duties certificates were
      significantly longer in duration than unfit-for-work certificates in all injury
      and illness categories (P < 0.001) but certificates for workers with
      musculoskeletal injuries and diseases, back pain and strains and other traumatic
      injuries were of lesser duration than those for workers with fractures, mental
      health conditions and other diseases. CONCLUSION: The high proportion of medical
      certificates recommending complete absence from work presents major challenges in
      terms of return to work, labour force productivity, the viability of the
      compensation system, and long-term social and economic development. There is
      substantial variation in the type and duration of medical certificates issued by
      GPs. People with mental health conditions are unlikely to receive a certificate
      recommending alternative duties. Further research is required to understand GP
      certification behaviour.

PMID- 24099210
TI  - General practitioners' use of different cardiovascular risk assessment
      strategies: a qualitative study.
AB  - OBJECTIVES: To identify factors that influence the extent to which general
      practitioners use absolute risk (AR) assessment in cardiovascular disease (CVD)
      risk assessment. DESIGN, SETTING AND PARTICIPANTS: Semi-structured interviews
      with 25 currently practising GPs from eight Divisions of General Practice in New
      South Wales, Australia, between October 2011 and May 2012. Data were analysed
      using framework analysis. RESULTS: The study identified five strategies that GPs
      use with patients in different situations, defined in terms of the extent to
      which AR was used and the reasons given for this: the AR-focused strategy, used
      when AR assessment was considered useful for the patient; the AR-adjusted
      strategy, used to account for additional risk factors such as family history; the
      clinical judgement strategy, used when GPs considered that their judgement took
      multiple risk factors into account as effectively as AR; the passive disregard
      strategy, used when GPs lacked sufficient time, access or experience to use AR;
      and the active disregard strategy, used when AR was considered to be
      inappropriate for the patient. The strategies were linked with different
      opportunity, capability and motivation barriers to the use of AR. CONCLUSIONS:
      This study provides an in-depth insight into the factors that influence GPs' use
      of AR in CVD risk assessment. The results suggest that GPs use a range of
      strategies in different situations, so different approaches may be required to
      improve the use of AR guidelines in practice.

PMID- 24099211
TI  - Mobile garbage bins and hand injuries in older people.
AB  - OBJECTIVES: To conduct a database search, chart and literature review of open
      extensor tendon and proximal interphalangeal joint injuries incurred while
      handling mobile garbage bins. DESIGN, SETTING AND PARTICIPANTS: A review of
      medical records at a Sydney tertiary referral hospital and a NSW rural Level 2
      trauma hospital from 1 January 2006 to 31 December 2010, identified through
      database searches of appropriate medical record codes and followed by a chart
      review. RESULTS: We identified 11 patients with finger injuries from handling
      mobile garbage bins that necessitated hospital-based treatments. Their average
      age was 75 years. Eight patients required surgery. Patients typically fell while
      maintaining their grip on mobile garbage bin handles, causing abrasive injury to
      the dorsal aspect of the proximal interphalangeal joint. CONCLUSIONS: Older
      patients are at risk of significant injuries to the dorsal side of their fingers
      when manoeuvring mobile garbage bins. This risk could be reduced by providing
      older members of the community with help to move their bins, or by modifying the
      design of bin handles. We propose a simple modification to the design of bin
      handles.

PMID- 24099212
TI  - Kawasaki disease complicated by subluxation of cervical vertebrae (Grisel
      syndrome).

PMID- 24099213
TI  - Khat-associated hepatitis.

PMID- 24099214
TI  - Australian Medical Students' Association Global Health Essay Competition - Global
      climate change, geo-engineering and human health.
AB  - Rio+20's proposed Sustainable Development Goals have the potential to redefine
      the course of international action on climate change. They recognise that
      environmental health is inextricably linked with human health, and that
      environmental sustainability is of paramount importance in safeguarding global
      health. Competition entrants were asked to discuss ways of making global health a
      central component of international sustainable development initiatives and
      environmental policy, using one or two concrete examples

PMID- 24099215
TI  - If you want to have joy, do.

PMID- 24099219
TI  - Simultaneous electrospinning and electrospraying: a straightforward approach for
      fabricating hierarchically structured composite membranes.
AB  - We present here for the first time a simple method for micropatterning nonwoven
      composite membranes. The approach is based on the simultaneous electrospraying of
      microparticles and electrospinning of nanofibers from different polymer solution
      feeds (polyethylene glycol and poly(D,L-lactide)) on a common support. The
      mechanism of self-organization between fibers and particles into hierarchical
      honeycomb-like structures, as well as the evolution of the later as a function of
      the thickness of the composite, is investigated. We demonstrate that aggregates
      of particles, leading to a nonuniform distribution of the electrostatic field
      near the collector, are necessary to form the self-organized composite.
      Furthermore, it is shown that the specific dimensions of the generated patterns
      can be controlled by tuning the flow rate of electrospraying. The obtained
      composite mat exhibits a multilevel porous structure, with pore sizes ranging
      from few up to several hundreds of micrometers. Finally, it is shown that the
      microparticles can be selectively leached, allowing the production of a
      monocomponent membrane and retaining the hierarchical organization of the
      nanofibers suitable for biomedical and filtration applications.

PMID- 24099220
TI  - Discovery of tryptanthrin derivatives as potent inhibitors of indoleamine 2,3
      dioxygenase with therapeutic activity in Lewis lung cancer (LLC) tumor-bearing
      mice.
AB  - Indoleamine 2,3-dioxygenase (IDO-1) is emerging as an important new therapeutic
      target for the treatment of cancer, neurological disorders, and other diseases
      that are characterized by pathological tryptophan metabolism. However, only a few
      structural classes are known to be IDO-1 inhibitors. In this study, a natural
      compound tryptanthrin was discovered to be a novel potent IDO-1 inhibitor by
      screening of indole-based structures. Three series of 13 tryptanthrin derivatives
      were synthesized, and the structure-activity analysis was undertaken. The
      optimization led to the identification of 5c, which exhibited the inhibitory
      activity at a nanomolar level. In vitro 5c dramatically augmented the
      proliferation of T cells. When administered to Lewis lung cancer (LLC) tumor
      bearing mice, 5c significantly inhibited IDO-1 activity and suppressed tumor
      growth. In addition, 5c reduced the numbers of Foxp3(+) regulatory T cells
      (Tregs), which are known to prevent the development of efficient antitumor immune
      responses. 

PMID- 24099221
TI  - A reason, a season or a lifetime? The importance of positive collegial
      relationships and networks in establishing career sustainability and resilience.

PMID- 24099222
TI  - Attributes of clinical leadership in contemporary nursing: an integrative review.
AB  - Effective clinical leadership is offered as the key to healthy, functional and
      supportive work environments for nurses and other health professionals. However,
      as a concept it lacks a standard definition and is poorly understood. This paper
      reports on an integrative review undertaken to uncover current understandings of
      defining attributes of contemporary clinical leadership in nursing. Data
      collection involved a search of relevant electronic databases for a 10-year
      period. Keywords for the search were 'clinical leadership' and 'nursing'. Ten
      research papers met the inclusion criteria for the integrative review. Analysis
      of these studies indicated clinical leadership attributes had a clinical focus, a
      follower/team focus or a personal qualities focus; attributes necessary to
      sustain supportive workplaces and build the capacity and resilience of nursing
      workforces. The small number of research-based studies yielded for the review
      indicates the need for further research in the area of clinical leadership.

PMID- 24099223
TI  - Finding a way forward: a literature review on the current debates around clinical
      supervision.
AB  - Nursing research increasingly calls for clinical supervision to support nurses
      and improve nursing practice. Despite this, clinical supervision is not well
      established in healthcare organisations. This paper employs a critical
      interpretive approach to review the clinical supervision literature. The review
      discusses the current debates and challenges exploring possible ways of moving
      beyond the current criticisms and limitations in the literature. The review
      concludes that despite some confusion about the quantifiable outcomes, clinical
      supervision presents a professionally enriching activity that provides a forum
      for sharing of knowledge and generation of shared understandings of health care.
      Through this shared experience it is possible that innovative and creative
      approaches to health care will be born.

PMID- 24099224
TI  - Continuing professional development in nursing in Australia: current awareness,
      practice and future directions.
AB  - Australian nurses and midwives are expected to compile a professional development
      portfolio during their annual registration process. This study aimed to ascertain
      the current understanding, practice and future continuing professional
      development (CPD) needs of nurses and midwives employed in a regional area of
      Queensland, Australia. Perceived barriers and incentives for CPD were also
      measured. 289 public and private hospital nurses and midwives responded to the
      survey. Results showed that participants understood the new requirements, valued
      ongoing learning, preferred education to occur within work hours, and considered
      their workplaces as accepting of change. Approximately two-thirds of participants
      believed CPD should be shared between them and their employers. Barriers to
      undertaking CPD included understaffing, and the concern that CPD would interfere
      with time outside work. Organisational support positively influenced attitudes to
      CPD. This study highlights the importance of supportive management in encouraging
      their workforce to embrace ongoing learning and change.

PMID- 24099225
TI  - 'I thought I was just going to teach': stories of new nurse academics on
      transitioning from sessional teaching to continuing academic positions.
AB  - Currently many nursing faculties and schools employ high numbers of sessional
      teachers to meet the demands of teaching. Sessional teachers are a source for
      future continuing academic staff; however, there is little exploration on the
      experiences of sessional teachers as they transition into the full-time nurse
      academic role. A qualitative study of 14 registered nurse participants used a
      story-telling approach to explore the experiences of sessional teachers as they
      transitioned into full-time and continuing academic roles. Findings revealed that
      participants had only a very limited understanding of the requirements of the
      academic role when appointed to it. Thematic analysis revealed two major themes.
      These were: 'Uncertainty: Dealing with role expectation' and 'Mitigating lack of
      confidence'. The implications of this paper contributes to and enhances knowledge
      of the transition experiences of sessional teachers and provides new evidence to
      suggest that adequate support processes are essential for sessional staff
      transitioning into permanent, full-time academic positions.

PMID- 24099226
TI  - Individual-level outcomes from a national clinical leadership development
      programme.
AB  - A national clinical leadership development programme was instituted for Irish
      nurses and midwives in 2010. Incorporating a development framework and leadership
      pathway and a range of bespoke interventions for leadership development,
      including workshops, action-learning sets, mentoring and coaching, the programme
      was introduced at seven pilot sites in the second half of 2011. The programme
      pilot was evaluated with reference to structure, process and outcomes elements,
      including individual-level programme outcomes. Evaluation data were generated
      through focus groups and group interviews, individual interviews and written
      submissions. The data provided evidence of nurses' and midwives' clinical
      leadership development through self and observer-reported behaviours and
      dispositions including accounts of how the programme participants developed and
      displayed particular clinical leadership competencies. A key strength of the new
      programme was that it involved interventions that focussed on specific leadership
      competencies to be developed within the practice context.

PMID- 24099227
TI  - Transition to work and the career destinations of double degree nurses.
AB  - Abstract One third of undergraduate nursing students in Australia are studying
      nursing concurrently with another undergraduate degree. This study examined the
      career preferences of double degree (DD) nursing students and the career
      destinations of graduates to gain an understanding of the reasons why nursing is
      chosen or not chosen. The design was a sequential mixed methods explanatory
      study. Questionnaires and interviews collected information during the final year
      of the DD, on commencement of work, and after 2 years in the workforce. Results
      revealed less than half of final year students indicated a preference for
      nursing, but 60-73% were employed in nursing after graduation. Career decisions
      were influenced by intrinsic and extrinsic rewards unique to nursing but also the
      other discipline. Practicum experiences and location of work were also important
      factors. Strategies are needed to avoid losing potential nursing graduates to
      other disciplines at a time of nursing staff shortages. 

PMID- 24099228
TI  - Primary health care as a philosophical and practical framework for nursing
      education: rhetoric or reality?
AB  - At least three decades after primary health care (PHC) took nursing by storm it
      is time to re-examine the philosophical shift to a PHC framework in pre
      registration nursing curricula and overview factors which may hinder or promote
      full integration of PHC as a course philosophy and a contemporary approach to
      professional practice. Whilst nurse education has traditionally focused on
      preparing graduates for practice in the acute care setting, there is continuing
      emphasis on preparing nurses for community based primary health roles, with a
      focus on illness prevention and health promotion. This is driven by growing
      evidence that health systems are not responding adequately to the needs and
      challenges of diverse populations, as well as economic imperatives to reduce the
      burden of disease associated with the growth of chronic and complex diseases and
      to reduce the costs associated with the provision of health care. Nursing pre
      registration programs in Australia and internationally have philosophically
      adopted PHC as a curriculum model for preparing graduates with the necessary
      competencies to function effectively across a range of settings. Anecdotal
      evidence, however, suggests that when adopted as a program philosophy PHC is not
      always well integrated across the curriculum. In order to develop a strong and
      resilient contemporary nursing workforce prepared for practice in both acute and
      community settings, pre-registration nursing programs need to comprehensively
      consider and address the factors impacting on the curricula integration of PHC
      philosophy.

PMID- 24099229
TI  - The health of nurses aged over 50 in New Zealand.
AB  - The mean age of registered nurses in New Zealand has been rising steadily, and
      40% are now aged 50 or over (Nursing Council of New Zealand [NCNZ], 2010).
      However little is known of this cohort's health-related quality of life. An
      anonymous on-line survey was emailed to nurses aged over 50 years and members of
      the New Zealand Nurses Organisation in February and March 2012. Quantitative and
      qualitative analyses of the 3,273 responses received were undertaken. Nurses aged
      over 50 remaining in the workforce report their health-related quality of life as
      better for all measures than standardised scores for age-matched women in New
      Zealand. Nurses working in more physical environments report higher pain scores
      than those working in less physical environments, and nurses reporting lower
      levels of health-related quality of life are more likely to retire sooner and to
      move to more casual and flexible hours of work as they age.

PMID- 24099230
TI  - Using appreciative inquiry to transform health care.
AB  - Amid tremendous changes in contemporary health care stimulated by shifts in
      social, economic and political environments, health care managers are challenged
      to provide new structures and processes to continually improve health service
      delivery. The general public and the media are becoming less tolerant of poor
      levels of health care, and health care professionals need to be involved and
      supported to bring about positive change in health care. Appreciative inquiry
      (AI) is a philosophy and method for promoting transformational change, shifting
      from a traditional problem-based orientation to a more strength-based approach to
      change, that focuses on affirmation, appreciation and positive dialog. This paper
      discusses how an innovative participatory approach such as AI may be used to
      promote workforce engagement and organizational learning, and facilitate positive
      organizational change in a health care context.

PMID- 24099231
TI  - Understanding moral habitability: a framework to enhance the quality of the
      clinical environment as a workplace.
AB  - There is compelling evidence in the nursing literature that the workplace is
      experienced as morally uninhabitable for many nurses and yet the concept of moral
      habitability remains underdeveloped. An integrative review on moral habitability
      in nursing was undertaken. The findings reveal that the primary concepts by which
      nurses write and research aspects of moral habitability are moral climate, moral
      agency, moral sensitivity and moral distress. It is revealed that nurses in their
      clinical work experience adversity and moral distress through relational
      challenges and contextual difficulties that can challenge habitability and
      inhibit nurses' capacity to provide morally sensitive patient care. The primary
      concepts identified provide a framework for further development of the concept of
      moral habitability within nursing practice. The related data within the
      integrative review also highlights the need for further research into enhancing
      and sustaining morally habitable workplaces for nurses.

PMID- 24099232
TI  - Enhancing the resilience of nurses and midwives: pilot of a mindfulness-based
      program for increased health, sense of coherence and decreased depression,
      anxiety and stress.
AB  - Health workers in general, and midwives and nurses in particular, experience high
      levels of stress/distress due to the nature of their work and workplaces; and,
      their socialization into ways of working that minimizes the likelihood of self
      care. Increasing interest in the development of resilient workers has meant an
      enormous growth in interest in the role of holistic practices such as mindfulness
      meditation. Kabat-Zinn's mindfulness-based stress reduction (MBSR) is one of the
      most commonly used by those seeking to practise, theorize or research mindfulness
      across multiple contexts. The primary aim of this study was to pilot the
      effectiveness of an adapted mindfulness-based stress reduction intervention on
      the psychological wellbeing of nurses and midwives. More specifically, we sought
      to test the acceptability and feasibility of a modified MBSR intervention to
      inform a future randomized controlled trial (RCT). The pilot study used a pre and
      post intervention design. Twenty midwives and 20 nurses participated in a one-day
      workshop, undertook to meditate daily for 8 weeks and completed pre and post
      intervention measures: general health questionnaire (GHQ-12); sense of coherence
      (SOC) - orientation to life and the depression, anxiety and stress scale (DASS).
      A subgroup took part in interviews or focus group discussions of their
      experiences of the program and their ongoing mindfulness practice. The
      quantitative findings included significant improvements on the GHQ-12, SOC and
      the stress subscale of the DASS. Qualitative findings support the acceptability
      of the intervention, and highlighted a number of issues related to feasibility of
      any future RCT. In conclusion, mindfulness practice holds promise for increasing
      individual and workplace resilience, however, meaningful research evidence from
      carefully constructed studies will be required to engage and motivate
      participation and organizational support.

PMID- 24099233
TI  - A good day in nursing: views of recent Singaporean graduates.
AB  - This paper arises from the analysis of data from a large Singapore-based survey
      and a complementary qualitative series of 17 individual interviews. Some results
      from both arms of the research have been previously analysed and are reported
      elsewhere. Answers to a series of questions within the questionnaire and the
      structured interviews have been drawn together under the umbrella of
      investigating of recent Singaporean graduates' views about the characteristics of
      a good nurse, a good day at work, and how they uphold ethical standards. Overall
      five themes emerged, these are: caring for others; respectful interpersonal
      interaction; rational clinical decision-making; the harsh reality of the
      workplace; and personal qualities (not easily influenced by formal education).
      Interviewees believed that potential nursing students should be made aware of the
      harsh realities they will face on graduation, which may seem counter-intuitive.
      However, graduates recalled their own struggles and perseverance and toughness to
      simply survive the early months as a key component of transition shock,
      indicating that an earlier awareness may be beneficial.

PMID- 24099234
TI  - Personal resilience in nurses and midwives: effects of a work-based educational
      intervention.
AB  - Nurses and midwives commonly face a variety of challenges and difficulties in
      their everyday work. Stress, pressure, fatigue and anxiety are acknowledged
      sources of workplace adversity, which causes decreased perceptions of health and
      wellbeing. This study reports the effects of a work-based, educational
      intervention to promote personal resilience in a group of 14 nurses and midwives
      working in a busy clinical environment. The intervention encouraged participants
      to focus on the key characteristics of a resilient person and the elements that
      assisted them in their maintenance of personal resilience. The intervention also
      explored potential strategies for the future. Opportunities were provided for
      experiential learning, creative self-expression and exposure to new ideas.
      Primary effects of the intervention were found to benefit the participants in
      personal and professional areas; by enhanced confidence, self-awareness,
      assertiveness and self-care. This intervention had implications for the education
      and practice of nurses and midwives in terms of building and maintaining their
      personal resilience, especially those exposed to workplace adversity.

PMID- 24099235
TI  - Self-assembly of short linear chains to A- and B-type starch spherulites and
      their enzymatic digestibility.
AB  - A novel process combining enzymatic debranching, melting, and crystallization was
      developed to produce spherulites from short linear alpha-1,4-linked glucans
      (short-chain amylose, SCA) with controlled enzyme digestibility. SCA was obtained
      by completely debranching waxy maize starch at 50  degrees C and 25% solids in
      0.01 M sodium acetate buffer. The mixture was then heated to 180  degrees C
      followed by cooling and crystallization to form well-developed spherulites.
      Multiple analytical techniques including light microscopy, scanning electron
      microscopy, differential scanning calorimetry, wide-angle X-ray diffraction, and
      synchrotron small-angle X-ray scattering (SAXS) covered over 5 orders of length
      scale and were applied to study the morphology and structure of the spherulites.
      Spherulites crystallized at low temperatures (4 and 25  degrees C) had a large
      size (5-10 MUm), a B-type starch X-ray diffraction pattern, a lower melting
      temperature (70-110  degrees C), and a higher digestibility (Englyst method)
      compared to the spherulites crystallized at 50  degrees C, which had a small size
      (1-5 MUm), an A-type diffraction pattern, a higher melting temperature (100-140 
      degrees C), and a lower digestibility. Intact spherulites along with small
      fragments were observed after digestion with a mixture of alpha-amyase and
      amyloglucosidase, indicating that digestion was not homogeneous and
      preferentially occurred in weak spherulites. A second exposure of the undigested
      residues to the amylases showed a similar digestive pattern as with the parent
      spherulites, suggesting that the spherulites were hydrolyzed by enzymes at
      essentially a constant digestion rate between 20 min and 3 h. 

PMID- 24099236
TI  - Progression of mild Alzheimer's disease: knowledge and prediction models required
      for future treatment strategies.
AB  - INTRODUCTION: Knowledge of longitudinal progression in mild Alzheimer's disease
      (AD) is required for the evaluation of disease-modifying therapies. Our aim was
      to observe the effects of long-term cholinesterase inhibitor (ChEI) therapy in
      mild AD patients in a routine clinical setting. METHODS: This was a prospective,
      open-label, non-randomized, multicenter study of ChEI treatment (donepezil,
      rivastigmine or galantamine) conducted during clinical practice. The 734 mild AD
      patients (Mini-Mental State Examination (MMSE) score 20 to 26) were assessed at
      baseline and then semi-annually over three years. Outcome measures included the
      MMSE, Alzheimer's Disease Assessment Scale-cognitive subscale (ADAS-cog),
      Clinician's Interview-Based Impression of Change (CIBIC) and Instrumental
      Activities of Daily Living (IADL) scale. RESULTS: After three years of ChEI
      therapy, 31% (MMSE) and 33% (ADAS-cog) of the patients showed improved/unchanged
      cognitive ability, 33% showed improved/unchanged global performance and 14%
      showed improved/unchanged IADL capacity. Higher mean dose of ChEI and lower
      educational level were both predictors of more positive longitudinal cognitive
      and functional outcomes. Older participants and those with a better IADL score at
      baseline exhibited a slower rate of cognitive decline, whereas younger
      participants and those with higher cognitive status showed more preserved IADL
      ability over time. Gender and apolipoprotein E (APOE) genotype showed
      inconsistent results. Prediction models using the abovementioned scales are
      presented. CONCLUSIONS: In naturalistic mild AD patients, a marked deterioration
      in IADL compared with cognitive and global long-term outcomes was observed,
      indicating the importance of functional assessments during the early stages of
      the disease. The participants' time on ChEI treatment before inclusion in studies
      of new therapies might affect their rate of decline and thus the comparisons of
      changes in scores between various studies. An increased understanding of expected
      disease progression in different domains and potential predictors of disease
      progression is essential for assessment of future therapies in AD.

PMID- 24099237
TI  - Effects of mosapride on secondary peristalsis in patients with ineffective
      esophageal motility.
AB  - OBJECTIVE. Ineffective esophageal motility is frequently found in patients with
      gastroesophageal reflux diseases. Secondary peristalsis contributes to esophageal
      acid clearance. Mosapride improves gastrointestinal (GI) motility by acting on 5
      hydroxytrypatamine4 receptors. The authors aimed to evaluate the effect of
      mosapride on secondary peristalsis in patients with ineffective esophageal
      motility. MATERIAL AND METHODS. After recording primary peristalsis baseline,
      secondary peristalsis was stimulated by slowly and rapidly injecting mid
      esophageal air in 18 patients. Two separate experiments were randomly performed
      with 40 mg oral mosapride or placebo. RESULTS. Mosapride had no effect on the
      threshold volume of secondary peristalsis during slow air distension (9.8 +/-
      0.97 vs. 10.2 +/- 1.0 mL; p = 0.84), but decreased the threshold volume during
      rapid air distension (4.1 +/- 0.2 vs. 4.6 +/- 0.3 mL; p = 0.001). The efficiency
      of secondary peristalsis during rapid air distension increased with mosapride
      (70% [40-95%]) compared with placebo (60% [10-85%]; p = 0.0003). Mosapride had no
      effect on the amplitudes of distal pressure wave of secondary peristalsis during
      slow (94.3 +/- 9 vs. 101.9 +/- 9.1 mmHg; p = 0.63) or rapid air distension (89.3
      +/- 9 vs. 95.2 +/- 8.3 mmHg; p = 0.24). CONCLUSIONS. Mosapride improves
      esophageal sensitivity of secondary peristalsis by abrupt air distension but has
      limited effect on the motor properties of secondary peristalsis in ineffective
      esophageal motility patients. Despite its well-known prokinetic effect, mosapride
      enhances the efficiency of secondary peristalsis in patients with ineffective
      esophageal motility through augmenting esophageal sensitivity instead of
      motility.

PMID- 24099238
TI  - The Brady Bunch reunion.

PMID- 24099241
TI  - Ten questions with .... Maria Cvach.

PMID- 24099243
TI  - Ask George.

PMID- 24099244
TI  - Changing faces.

PMID- 24099245
TI  - The essentials of medical device inventory tracking.

PMID- 24099246
TI  - Do tell: using the power of storytelling to grow on the job.

PMID- 24099247
TI  - Living and dying in modern medicine: a patient interviews her doctor.

PMID- 24099248
TI  - The trusting relationship between HTM professionals and nurses.

PMID- 24099249
TI  - A nurse's take on the role of healthcare technology management.

PMID- 24099250
TI  - Understanding EQ56: standard sets 'minimum expectations' for equipment management
      programs.

PMID- 24099251
TI  - Great expectations: the road toward improved digital images.

PMID- 24099252
TI  - Hospital CIO tackles challenge of EHRs.

PMID- 24099253
TI  - A matter of security.

PMID- 24099254
TI  - Curtailing device abuse and limiting repairs.

PMID- 24099255
TI  - The importance of imaging technology.

PMID- 24099256
TI  - Clean benches.

PMID- 24099257
TI  - A look at clinical decision support systems.

PMID- 24099258
TI  - Understanding ventilators.

PMID- 24099259
TI  - Medical equipment maintenance abroad.

PMID- 24099261
TI  - Safety vs. safety.

PMID- 24099262
TI  - Probiotics in cirrhosis: do we expect too much?

PMID- 24099263
TI  - If portal hypertension predicts outcome in cirrhosis, why should this not be the
      case after surgical resection?

PMID- 24099264
TI  - The impact of a pay-for-performance system on timing to hip fracture surgery:
      experience from the Lazio Region (Italy).
AB  - BACKGROUND: A tariff modulation mechanisms has been introduced in some Italian
      regions with the aim of reducing inappropriate admissions and improving quality
      of care. In response to a regional act, hospitals in Lazio adopted a clinical
      pathway for elderly patients with hip fracture and introduced a compensation
      system based on the quality of health care, as in a pay-for-performance model.
      The objective of the present study was to compare the proportion of surgery for
      hip fracture performed within 48 hours of admission among Lazio hospitals
      according to different payment systems, before and after the implementation of
      the regional act. METHODS: A retrospective cohort study of patients aged 65 years
      and over, residing in the Lazio region and admitted to an acute care hospital for
      hip fracture before (1 July 2008 - 30 June 2009) and after (1 July 2010 - 30 June
      2011) the pay-for-performance act. The proportion of surgeries performed within
      48 h of hospital arrival was calculated. An adjusted multivariate regression
      analysis was applied to assess the effect of hospital payment type on the
      likelihood of surgery within 48 h of hospital arrival. RESULTS: The share of
      patients with hip fracture that had surgery within 48 hours was 11.7% before the
      introduction of the pay-for-performance act and 22.2% after. The proportion of
      early hip fracture operations increased after the pay-for-performance act,
      regardless of hospital payment type. The largest increase of surgery within 48 h
      occurred in private hospitals (adjusted Relative Risk = 2.80, p < 0.001).
      CONCLUSIONS: The introduction of a compensation system based on health care
      quality is associated with improved quality of care for elderly patients with hip
      fracture, especially in hospitals that only use the Diagnosis Related Group
      system.

PMID- 24099265
TI  - Translating the N-methyl-D-aspartate receptor antagonist model of schizophrenia
      to treatments for cognitive impairment in schizophrenia.
AB  - The N-methyl-D-aspartate receptor (NMDAR) antagonists, phencyclidine (PCP),
      dizocilpine (MK-801), or ketamine, given subchronically (sc) to rodents and
      primates, produce prolonged deficits in cognitive function, including novel
      object recognition (NOR), an analog of human declarative memory, one of the
      cognitive domains impaired in schizophrenia. Atypical antipsychotic drugs (AAPDs)
      have been reported to improve declarative memory in some patients with
      schizophrenia, as well as to ameliorate and prevent the NOR deficit in rodents
      following scNMDAR antagonist treatment. While the efficacy of AAPDs to improve
      cognitive impairment in schizophrenia (CIS) is limited, at best, and
      controversial, single doses of all currently available AAPDs so far tested
      transiently restore NOR in rodents following scNMDAR antagonist treatment.
      Typical antipsychotic drugs (APDs), e.g. haloperidol and perphenazine, are
      ineffective in this rodent model, and may be less effective as treatments of some
      domains of CIS. Serotonergic mechanisms, including, but not limited to serotonin
      (5-HT)2A and 5-HT7 antagonism, 5-HT(1A), and GABA(A) agonism, contribute to the
      efficacy of the AAPDs in the scNMDAR antagonist rodent models, which are relevant
      to the loss of GABA interneuron/hyperglutamate hypothesis of the etiology of CIS.
      The ability of sub-effective doses of the atypical APDs to ameliorate NOR in the
      scNMDAR-treated rodents can be restored by the addition of a sub-effective dose
      of the 5-HT(1A) partial agonist, tandospirone, or the 5-HT7 antagonist, SB269970.
      The mGluR2/3 agonist, LY379268, which itself is unable to restore NOR in the
      scNMDAR-treated rodents, can also restore NOR when given with lurasidone, an
      AAPD. Enhancing cortical and hippocampal dopamine and acetylcholine efflux, or
      both, may contribute to the restoration of NOR by the atypical APDs. Importantly,
      co-administration of lurasidone, tandospirone, or SB269970, with PCP, to rodents,
      at doses 5-10 fold greater than those acutely effective to restore NOR following
      scNMDAR treatment, prevents the effect of scPCP to produce an enduring deficit in
      NOR. This difference in dosage may be relevant to utilizing AAPDs to prevent the
      onset of CIS in individuals at high risk for developing schizophrenia. The
      scNMDAR paradigm may be useful for identifying possible means to treat and
      prevent CIS.

PMID- 24099266
TI  - Linking habitat selection and predation risk to spatial variation in survival.
AB  - A central assumption underlying the study of habitat selection is that selected
      habitats confer enhanced fitness. Unfortunately, this assumption is rarely
      tested, and in some systems, gradients of predation risk may more accurately
      characterize spatial variation in vital rates than gradients described by habitat
      selection studies. Here, we separately measured spatial patterns of both resource
      selection and predation risk and tested their relationships with a key
      demographic trait, adult female survival, for a threatened ungulate, woodland
      caribou (Rangifer tarandus caribou Gmelin). We also evaluated whether exposure to
      gradients in both predation risk and resource selection value was manifested
      temporally through instantaneous or seasonal effects on survival outcomes. We
      used Cox proportional hazards spatial survival modelling to assess the relative
      support for 5 selection- and risk-based definitions of habitat quality, as
      quantified by woodland caribou adult female survival. These hypotheses included
      scenarios in which selection ideally mirrored survival, risk entirely drove
      survival, non-ideal selection correlated with survival but with additive risk
      effects, an ecological trap with maladaptive selection and a non-spatial effect
      of annual variation in weather. Indeed, we found positive relationships between
      the predicted values of a resource selection function (RSF) and survival, yet
      subsequently incorporating an additional negative effect of predation risk
      greatly improved models further. This revealed a positive, but non-ideal
      relationship between selection and survival. Gradients in these covariates were
      also shown to affect individual survival probability at multiple temporal scales.
      Exposure to increased predation risk had a relatively instantaneous effect on
      survival outcomes, whereas variation in habitat suitability predicted by an RSF
      had both instantaneous and longer-term seasonal effects on survival. Predation
      risk was an additive source of hazard beyond that detected through selection
      alone, and woodland caribou selection thus was shown to be non-ideal.
      Furthermore, by combining spatial adult female survival models with herd-specific
      estimates of recruitment in matrix population models, we estimated a spatially
      explicit landscape of population growth predictions for this endangered species. 

PMID- 24099267
TI  - On the environmental health effects and socio-economic considerations of the
      potential listing of short-chain chlorinated paraffins into the Stockholm
      Convention on Persistent Organic Pollutants.

PMID- 24099268
TI  - Activation of mammalian target of rapamycin mediates rat pain-related responses
      induced by BmK I, a sodium channel-specific modulator.
AB  - The mammalian target of rapamycin (mTOR) is known to regulate cell proliferation
      and growth by controlling protein translation. Recently, it has been shown that
      mTOR signaling pathway is involved in long-term synaptic plasticity. However, the
      role of mTOR under different pain conditions is less clear. In this study, the
      spatiotemporal activation of mTOR that contributes to pain-related behaviors was
      investigated using a novel animal inflammatory pain model induced by BmK I, a
      sodium channel-specific modulator purified from scorpion venom. In this study,
      intraplantar injections of BmK I were found to induce the activation of mTOR, p70
      ribosomal S6 protein kinase (p70 S6K) and eukaryotic initiation factor 4E-binding
      protein 1 (4E-BP1) in rat L5-L6 spinal neurons. In the spinal cord, mTOR, p70 S6K
      and 4E-BP1 were observed to be activated in the ipsilateral and contralateral
      regions, peaking at 1-2 h and recovery at 24 h post-intraplantar (i.pl.) BmK I
      administration. In addition, intrathecal (i.t.) injection of rapamycin - a
      specific inhibitor of mTOR - was observed to result in the reduction of
      spontaneous pain responses and the attenuation of unilateral thermal and
      bilateral mechanical hypersensitivity elicited by BmK I. Thus, these results
      indicate that the mTOR signaling pathway is mobilized in the induction and
      maintenance of pain-activated hypersensitivity. 

PMID- 24099269
TI  - Rationale, design and methods for a community-based study of clustering and
      cumulative effects of chronic disease processes and their effects on ageing: the
      Busselton healthy ageing study.
AB  - BACKGROUND: The global trend of increased life expectancy and increased
      prevalence of chronic and degenerative diseases will impact on health systems. To
      identify effective intervention and prevention strategies, greater understanding
      of the risk factors for and cumulative effects of chronic disease processes and
      their effects on function and quality of life is needed.The Busselton Healthy
      Ageing Study aims to enhance understanding of ageing by relating the clustering
      and interactions of common chronic conditions in adults to function. Longitudinal
      (3-5 yearly) follow-up is planned. METHODS/DESIGN: Phase I (recruitment) is a
      cross-sectional community-based prospective cohort study involving up to 4,000
      'Baby Boomers' (born from 1946 to 1964) living in the Busselton Shire, Western
      Australia. The study protocol involves a detailed, self-administered health and
      risk factor questionnaire and a range of physical assessments including body
      composition and bone density measurements, cardiovascular profiling (blood
      pressure, ECG and brachial pulse wave velocity), retinal photography, tonometry,
      auto-refraction, spirometry and bronchodilator responsiveness, skin allergy prick
      tests, sleep apnoea screening, tympanometry and audiometry, grip strength,
      mobility, balance and leg extensor strength. Cognitive function and reserve,
      semantic memory, and pre-morbid intelligence are assessed. Participants provide a
      fasting blood sample for assessment of lipids, blood glucose, C-reactive protein
      and renal and liver function, and RNA, DNA and serum are stored. Clinically
      relevant results are provided to all participants. The prevalence of risk
      factors, symptoms and diagnosed illness will be calculated and the burden of
      illness will be estimated based on the observed relationships and clustering of
      symptoms and illness within individuals. Risk factors for combinations of illness
      will be compared with those for single illnesses and the relation of combinations
      of illness and symptoms to cognitive and physical function will be estimated.
      DISCUSSION: This study will enable a thorough characterization of multiple
      disease processes and their risk factors within a community-based sample of
      individuals to determine their singular, interactive and cumulative effects on
      ageing. The project will provide novel cross-sectional data and establish a
      cohort that will be used for longitudinal analyses of the genetic, lifestyle and
      environmental factors that determine whether an individual ages well or with
      impairment.

PMID- 24099270
TI  - Self-digitization of samples into a high-density microfluidic bottom-well array.
AB  - This paper describes a sample digitization method that generates tens of
      thousands of nanoliter-sized droplets in a high-density array in a matter of
      minutes. We show that the sample digitization depends on both the geometric
      design of the microfluidic device and the viscoelastic forces between the aqueous
      sample and a continuous oil phase. Our design avoids sample loss: Samples are
      split into tens of thousands of discrete volumes with close to 100% efficiency
      without the need for any expensive valving or pumping systems. We envision this
      technology will have broad applications that require simple sample digitization
      within minutes, such as digital polymerase chain reactions and single-cell
      studies. 

PMID- 24099271
TI  - Dynamics of dilute solutions of poly(aspartic acid) and its sodium salt
      elucidated from atomistic molecular dynamics simulations with explicit water.
AB  - The use of forward osmosis (FO) process for seawater desalination has attracted
      tremendous interest in recent years. Besides the manufacture of suitable
      membranes, the major technical challenge in the efficient deployment of the FO
      technology lies in the development of a suitable "draw solute". Owing to its
      inherent advantages, poly(aspartic acid) has arisen to be an attractive candidate
      for this purpose. However, an investigation of its molecular level properties has
      not been studied in detail. In this paper, the dynamics of poly(aspartic acid)
      and its sodium salt in the dilute concentration regime have been reported. The
      quantification of the polymer conformational properties, its solvation behavior,
      and the counterion dynamics are studied. The neutral polymer shows a
      preferentially coiled structure whereas the fully ionized polymer has an extended
      structure. Upon comparing with poly(acrylic acid) polymer, another polymer which
      has been used as a draw solute, poly(aspartic acid) forms more number of hydrogen
      bonds as well as fewer ion pairs. 

PMID- 24099272
TI  - Chronic myeloid leukemia (CML): association of treatment satisfaction, negative
      medication experience and treatment restrictions with health outcomes, from the
      patient's perspective.
AB  - BACKGROUND: The availability of the tyrosine-kinase inhibitor (TKI), imatinib,
      and later introduction of second generation TKIs, dasatinib and nilotinib, have
      not only improved clinical outcomes of patients with chronic myeloid leukemia
      (CML), but also provide multiple therapeutic options for CML patients. Despite
      the widespread use of these oral therapies, little is known about the impact of
      different treatment regimens on patient-reported outcomes (PROs) among CML
      patients. The objective of this study was to assess the impact of patient
      reported treatment restrictions and negative medication experiences (NMEs) on
      satisfaction and other health outcomes among patients with CML treated with oral
      TKIs. METHODS: Participants recruited from survey panels and patient networks in
      the United States (US) and Europe completed an online questionnaire. Respondents
      included adults (>= 18 years) with chronic-phase CML currently on TKI treatment.
      Study variables included treatment difficulty (i.e., difficulty in following
      treatment regimens), CML dietary/dosing requirements, NMEs, and validated PROs
      assessing treatment satisfaction, health-related quality of life (HRQoL),
      activity impairment, and non-adherence. Structural equation models assessed
      associations among variables, controlling for covariates. RESULTS: 303 patients
      with CML (US n=152; Europe n=151; mean age 51.5 years; 46.2% male) completed the
      questionnaire. Approximately 30% of patients reported treatment difficulties;
      treatment difficulty was higher among nilotinib (63.3%) than among dasatinib
      (2.6%) or imatinib (19.2%) treated patients (p<0.0001). Non-adherence was
      generally low; however, patients on nilotinib vs. imatinib reported missing doses
      more often (p<0.05). Treatment satisfaction was associated with significantly
      increased HRQoL (p<0.05) and lower activity impairment (p<0.01). NMEs were
      associated with decreased treatment satisfaction (p<0.01) and HRQoL (p<0.05), and
      greater activity impairment (p<0.01). Higher overall treatment restrictions were
      associated with greater treatment difficulty (p<0.001), which correlated with non
      adherence (p<0.01). CONCLUSIONS: Treatment satisfaction and NMEs are important
      factors associated with HRQoL among patients with CML. Increased treatment
      restrictions and associated difficulty may affect adherence with TKIs. Choosing a
      CML treatment regimen that is simple and conveniently adaptable in patients'
      normal routine can be an important determinant of HRQoL and adherence.

PMID- 24099273
TI  - Identification of potential target genes of butyrate in dimethylhydrazine-induced
      colorectal cancer in mice.
AB  - The mechanism by which butyrate prevents colorectal cancer (CRC) is unclear. The
      objective of this study was to identify potential target genes of butyrate in 1,2
      dimethylhydrazine (DMH)-induced CRC in mice. Nontumor colorectal tissues of mice
      from DMH + butyrate, DMH, and control groups were hybridized on Agilent Mouse
      Whole Genome 44K Oligo Microarrays. Selected genes were validated by qRT-PCR.
      Data was further analyzed by KEGG, gene ontology (GO), and pathway studio
      software. The tumor incidence in the DMH + butyrate and DMH groups was 30% and
      90%, respectively (P < 0.05). There were 355 genes downregulated due to DMH
      treatment while upregulated by butyrate, and 475 genes upregulated by DMH while
      downregulated by butyrate. The results revealed that most of the tumor-related
      signaling pathways (e.g., MAPK pathway, Wnt pathway, insulin pathway, and VEGF
      pathway) were downregulated by butyrate. The GO terms related to cell
      differentiation, cell cycle, cell proliferation, cell death, cell adhesion, and
      cell migration were significantly affected. The chemopreventive effects of
      butyrate were confirmed in the DMH-induced CRC mice model. And mechanisms
      encompassing multiple pathways and GO terms are involved in the regulation of
      gene expression. 

PMID- 24099274
TI  - Metamorphopsia and optical coherence tomography findings after rhegmatogenous
      retinal detachment surgery.
AB  - PURPOSE: To investigate the relationship between metamorphopsia and macular
      morphologic changes after successful repair of rhegmatogenous retinal detachment
      (RD). DESIGN: Prospective, interventional, consecutive study. METHODS: The study
      included 129 eyes of 129 patients who had undergone successful retinal
      reattachment surgery. The severity of metamorphopsia was recorded using M-CHARTS
      and foveal microstructure was assessed with spectral-domain optical coherence
      tomography (OCT) at 6-12 months postoperatively. RESULTS: The mean metamorphopsia
      score was 0.30 +/- 0.46, and 50 of 129 patients (39%) had metamorphopsia.
      Metamorphopsia was more severe in eyes with macula-off rhegmatogenous RD than
      those with macula-on (P < .001). Eighteen of 50 eyes with metamorphopsia
      exhibited abnormal structures in the macular region (epiretinal membrane,
      disruption of the photoreceptor inner and outer segment junction, cystoid macular
      edema, macular hole, or subretinal fluid), whereas the other 32 eyes showed no
      morphologic changes with OCT. In these 32 eyes, the horizontal metamorphopsia
      score (0.86 +/- 0.50) was significantly higher than the vertical metamorphopsia
      score (0.62 +/- 0.39, P < .05). Nine of 69 eyes with preoperative macula-on
      rhegmatogenous RD developed postoperative metamorphopsia. Of the 9 eyes, 6 showed
      abnormal macular structures and the other 3 had normal-appearing OCT. The macula
      briefly detached during vitrectomy in these 3 cases. CONCLUSIONS: In eyes that
      remained macula-on throughout surgery and had normal-appearing OCT,
      metamorphopsia did not develop. In some cases, the reason for metamorphopsia was
      anatomically obvious. In other cases that were preoperative and intraoperative
      macula-off, postoperative retinal vertical displacement could cause predominantly
      horizontal metamorphopsia.

PMID- 24099275
TI  - Intraocular lens power calculation by ray-tracing after myopic excimer laser
      surgery.
AB  - PURPOSE: To investigate the refractive outcomes of intraocular lens (IOL) power
      calculation by ray-tracing after myopic excimer laser surgery. DESIGN:
      Prospective, interventional case series. METHODS: setting: Multicenter study.
      participants: Twenty-one eyes of 21 patients undergoing phacoemulsification and
      IOL implantation after myopic laser in situ keratomileusis or photorefractive
      keratectomy were enrolled. intervention: IOL power calculation was performed
      using internal software of a Scheimpflug camera combined with a Placido disc
      corneal topographer (Sirius; CSO). Exact ray-tracing was carried out after the
      axial length (measured either by immersion ultrasound biometry or partial
      coherence interferometry), target refraction, and pupil size had been entered.
      main outcome measures: Median absolute error, mean absolute error, and mean
      arithmetic error in refraction prediction, that is, the difference between the
      expected refraction (as calculated by the software) and the actual refraction 1
      month after surgery. RESULTS: The mean postoperative refraction was -0.43 +/-
      1.08 diopters (D), with a range between -1.28 and 0.85 D. The mean arithmetic
      error was -0.13 +/- 0.49 D. The median and mean absolute errors were +0.25 D and
      0.36 D, respectively. Also, 71.4% of the eyes were within +/- 0.50 D of the
      predicted refraction, 85.7% were within +/- 1.00 D, and 100% within +/- 1.50 D.
      CONCLUSIONS: Ray-tracing can calculate IOL power accurately in eyes with prior
      myopic laser in situ keratomileusis and photorefractive keratectomy, with no need
      for preoperative data.

PMID- 24099276
TI  - Epidemiology and disease burden of pathologic myopia and myopic choroidal
      neovascularization: an evidence-based systematic review.
AB  - PURPOSE: To summarize the epidemiology of pathologic myopia and myopic choroidal
      neovascularization (CNV) and their impact on vision. DESIGN: Systematic
      literature review of all English-language studies evaluating the epidemiology and
      visual burden of pathologic myopia or myopic CNV. METHODS: PubMed and EMBASE were
      searched with no time limits using predefined search strings for English-language
      studies evaluating the epidemiology and visual burden of pathologic myopia and
      myopic CNV. RESULTS: In total, 39 relevant publications were identified.
      Population-based studies reported pathologic myopia to be the first to third most
      frequent cause of blindness. The prevalence of pathologic myopia was reported to
      be 0.9%-3.1%, and the prevalence of visual impairment attributable to pathologic
      myopia ranged from 0.1%-0.5% (European studies) and from 0.2%-1.4% (Asian
      studies). The prevalence of CNV in individuals with pathologic myopia was
      reported to be 5.2%-11.3%, and was bilateral in approximately 15% of patients.
      All studies of visual outcome in patients with myopic CNV (duration ranging from
      less than 3 months to 21.5 years) reported deterioration in best-corrected visual
      acuity over time. Older age, subfoveal CNV location, and larger baseline lesion
      size were predictors of worse visual outcomes. CONCLUSIONS: Pathologic myopia is
      an important cause of vision loss worldwide, affecting up to 3% of the
      population. Of these, a substantial proportion of patients develop myopic CNV,
      which mostly causes a significant progressive decrease in visual acuity. This
      condition should therefore be a target for new treatment strategies.

PMID- 24099277
TI  - Evaluation of levator function for efficacy of minimally invasive and standard
      techniques for involutional ptosis.
AB  - PURPOSE: To evaluate clinical and anatomic outcomes of surgery for involutional
      ptosis using standard-length or small incisions in relation to preoperative
      levator function. DESIGN: Retrospective study. METHODS: Sixty-three patients
      diagnosed with involutional ptosis who underwent surgical correction using a
      small or standard-length incision between November 2010 and December 2011 were
      reviewed; a single surgeon performed surgery using a small incision (8 to 10 mm)
      in 22 patients and a standard-length incision (20 to 22 mm) in 34 patients. All
      patients underwent standard preoperative ptosis evaluation with margin-to-reflex
      distance 1 and 2 measurements and levator function assessment. Patients were
      divided into 2 groups according to levator function (moderate: 5 to 10 mm; and
      good: >10 mm). Surgical success was evaluated based on the British Oculoplastic
      Surgery Society criteria. RESULTS: Of 83 upper eyelids of 63 patients, surgery
      was performed using a small incision in 40 and a standard incision in 43. In
      patients with good levator function, surgical success was achieved with a small
      incision in 18 eyelids (94.7%) and a standard incision in 20 eyelids (95.2%; P =
      .91). In patients with moderate levator function, surgical success was achieved
      with a small incision in 14 eyelids (66.7%) and with a standard incision in 18
      eyelids (81.8%; P = .04). CONCLUSIONS: These findings indicate a similar surgical
      success rate in patients with good levator function, regardless of incision
      length. The surgical success rate in patients with moderate levator function was
      lower when using a small incision, perhaps because of decreased visualization and
      anatomic access.

PMID- 24099279
TI  - Impact of food and the proton pump inhibitor rabeprazole on the pharmacokinetics
      of GDC-0941 in healthy volunteers: bench to bedside investigation of pH-dependent
      solubility.
AB  - GDC-0941 is an orally administered potent, selective pan-inhibitor of
      phosphatidylinositol 3-kinases (PI3Ks) with good preclinical antitumor activity
      in xenograft models and favorable pharmacokinetics and tolerability in phase 1
      trials, and it is currently being investigated in phase II clinical trials as an
      anti-cancer agent. In vitro solubility and dissolution studies suggested that GDC
      0941, a weak base, displays significant pH-dependent solubility. Moreover,
      preclinical studies conducted in famotidine-induced hypochlorhydric dog suggested
      that the pharmacokinetics of GDC-0941 may be sensitive to pharmacologically
      induced hypochlorhydria. To investigate the clinical significance of food and pH
      dependent solubility on GDC-0941 pharmacokinetics a four-period, two-sequence,
      open-label, randomized, crossover study was conducted in healthy volunteers.
      During the fasting state, GDC-0941 was rapidly absorbed with a median Tmax of 2
      h. The presence of a high-fat meal delayed the absorption of GDC-0941, with a
      median Tmax of 4 h and a modest increase in AUC relative to the fasted state,
      with an estimated geometric mean ratio (GMR, 90% CI) of fed/fasted of 1.28 (1.08,
      1.51) for AUC0-infinity and 0.87 (0.70, 1.06) for Cmax. The effect of rabeprazole
      (model PPI) coadministration on the pharmacokinetics of GDC-0941 was evaluated in
      the fasted and fed state. When comparing the effect of rabeprazole + GDC-0941
      (fasted) to baseline GDC-0941 absorption in a fasted state, GDC-0941 median Tmax
      was unchanged, however, both Cmax and AUC0-infinity decreased significantly after
      pretreatment with rabeprazole, with an estimated GMR (90% CI) of 0.31 (0.21,
      0.46) and 0.46 (0.35, 0.61), respectively for both parameters. When rabeprazole
      was administered in the presence of the high-fat meal, the impact of food did not
      fully reverse the pH effect; the overall effect of rabeprazole on AUC0-infinity
      was somewhat attenuated by the high-fat meal (estimate GMR of 0.57, with 90% CI,
      0.50, 0.65) but unchanged for the Cmax (estimate of 0.43, with 90% CI, 0.37,
      0.50). The results of the current investigations emphasize the complex nature of
      physicochemical interactions and the importance of gastric acid for the
      dissolution and solubilization processes of GDC-0941. Given these findings,
      dosing of GDC-0941 in clinical trials was not constrained relative to fasted/fed
      states, but the concomitant use of ARAs was restricted. Mitigation strategies to
      limit the influence of pH on exposure of molecularly targeted agents such as GDC
      0941 with pH-dependent solubility are discussed. 

PMID- 24099278
TI  - KRT12 mutations and in vivo confocal microscopy in two Japanese families with
      Meesmann corneal dystrophy.
AB  - PURPOSE: To identify genetic mutations and study the corneal epithelium in
      Japanese patients with Meesmann corneal dystrophy. DESIGN: Laboratory
      investigation and prospective observational case series. METHODS: Slit-lamp
      biomicroscopy with fluorescein vital staining and in vivo confocal microscopy
      were performed. Mutation screening of the KRT3 and KRT12 genes was performed via
      polymerase chain reaction and direct sequencing for 5 patients in 2 families.
      RESULTS: Slit-lamp biomicroscopy revealed multiple corneal intraepithelial
      microcysts in all patients. A clear zone was seen in the younger generation,
      whereas mild subepithelial opacity was seen in the older generation. In the in
      vivo confocal microscopy, numerous corneal intraepithelial microcysts and
      hyperreflective materials, which were believed to be degenerative cells, were
      detected closer to the basal layer of the corneal epithelium in older patients.
      The superficial layer contained more enlarged microcysts, and the hyperreflective
      materials showed atrophic changes, as compared to the basal layer. The
      demarcation line between the microcysts and normal epithelial cells was clearly
      visualized by in vivo confocal microscopy and corresponded to the demarcation
      line of the clear zone observed by the slit-lamp examination. Two heterozygous
      mutations (Q130P, L140Q) in the KRT12 gene, one of which (L140Q) was novel, were
      identified only in the affected patients of the families. CONCLUSIONS: We
      identified a novel missense mutation of the KRT12 gene in Meesmann corneal
      dystrophy. The in vivo confocal microscopy examinations revealed previously
      unreported depth-dependent ultrastructural changes in the living cornea of
      Meesmann corneal dystrophy patients.

PMID- 24099280
TI  - Polymorphism Analysis of VSX1 and SOD1 Genes in Greek Patients with Keratoconus.
AB  - BACKGROUND: A number of mutations in the VSX1 and SOD1 genes have been reported
      to be associated with keratoconus (KC), however the results from different
      studies are controversial. In this study, we conducted the genotyping of common
      polymorphisms [VSX1: D144E, H244R, R166W, G160D; SOD1: intronic 7-base deletion
      (c.169 + 50 delTAAACAG)], in a case-control sample panel of the Greek population.
      MATERIALS AND METHODS: A case-control panel, with 33 KC patients and 78 healthy
      controls, were surveyed. DNA from each individual was tested for the VSX1: D144E,
      H244R, R166W, G160D and SOD1: intronic 7-base deletion (c.169 + 50 delTAAACAG)
      polymorphisms by direct sequencing. RESULTS: We observed no polymorphisms of the
      VSX1 gene in the case-control panel. Concerning the SOD1 intronic 7-base deletion
      (c.169 + 50 delTAAACAG), our findings suggest that heterozygous carriers are over
      represented among KC cases compared to healthy controls (p = 0.002). CONCLUSIONS:
      We cannot confirm the previously reported association of the polymorphism in the
      VSX1 gene with KC. Our results suggest a possible causative role of SOD1 in the
      pathogenesis of KC. Further studies are required to identify other important
      genetic factors involved in the pathogenesis and progression of KC.

PMID- 24099281
TI  - CYP1B1 Mutations are a Major Contributor to Juvenile-Onset Open Angle Glaucoma in
      Saudi Arabia.
AB  - To describe the genotype and phenotype in 14 unrelated Saudis with juvenile open
      angle glaucoma (JOAG). Detailed clinical examination was carried out and we
      sequenced cytochrome P450, family 1, subfamily B (CYP1B1), Myocilin (MYOC) and
      latent-transforming growth factor beta-binding protein 2 (LTBP2) genes. Twelve
      (85.7%) patients had apparent sporadic inheritance and 2 (14.3%) presented with a
      family history of glaucoma. Overall, 12 patients (85.7%) had CYP1B1 mutation.
      Nine patients had CYP1B1 mutations in a homozygous status. Eight of these had
      homozygous p.G61E mutation and one had a silent (no amino acid change) sequence
      change. Two patients had p.G61E mutation in a compound heterozygous status with
      another CYP1B1 mutation (p.L432V). Two patients had p.G61E in a heterozygous
      status with no other mutation, while one patient had no mutation(s). None of the
      patients had any mutation(s) in the MYOC or LTBP2 genes. JOAG associated with
      CYP1B1 mutations occurs at a high rate in the Saudi population. A specific
      genotype-phenotype relationship was not demonstrated. 

PMID- 24099283
TI  - Nickel-catalyzed C-P cross-coupling of arylboronic acids with P(O)H compounds.
AB  - A novel and efficient Ni-catalyzed coupling of a wide range of arylboronic acids
      with H-phosphites, H-phosphinate esters, and H-phosphine oxides has been
      developed, providing a general and powerful tool for the synthesis of various
      aryl-phosphorus compounds, especially for valuable triarylphosphine oxides, in
      good to excellent yield. This protocol is the first Ni-catalyzed C-P bond-forming
      reaction between arylboronic acids and P(O)H compounds. 

PMID- 24099282
TI  - Predominance of Klebsiella pneumoniae ST14 carrying CTX-M-15 causing neonatal
      sepsis in Tanzania.
AB  - BACKGROUND: Klebsiella pneumoniae strains expressing ESBLs are a predominant
      cause of hospital acquired infections. Here we describe the molecular
      epidemiology of these isolates in a tertiary hospital in Tanzania, as potential
      pathogens for neonatal infections. METHODS: Between April 2009 and March 2010 all
      Klebsiella pneumoniae isolates with phenotypic expression Extended Spectrum Beta
      Lactamase (ESBL) were collected and characterized. Identification was done using
      in house biochemical tests in case of ambiguous results confirmation was done
      using API 20E. Susceptibility testing was determined using the disc diffusion
      method followed by specific PCR and sequencing to determine ESBL genes.
      Phylogenetic analysis, Pulse field gel electrophoresis (PFGE) and Multi-Locus
      sequence typing (MLST) to PFGE clusters representative isolates were performed to
      determine clones of the isolates. Conjugation and hybridization were performed to
      determine the location of blaCTX-M-15 gene. RESULTS: A total of 92 non-repetitive
      ESBL producing K. pneumoniae representing 50.3% of Klebsiella pneumoniae isolates
      were characterized. These isolates were from blood 61 (66%), wound swab 13 (14%),
      urine 12 (13%) and pus 6 (7%) were analyzed. Most blood culture strains
      originated from neonatal unit 39/61(64%) and 22 (36%) of the blood culture
      isolates were from neonatal ICU. All isolates were resistant to gentamicin and
      54% were resistant to ciprofloxacin. Using a similarity index of 80%, the
      isolates were assigned to thirteen clusters based on PFGE patterns and contained
      sub-clusters with identical strains indicating clonal outbreaks. Cluster X5, X7
      and X8, and X9 were grouped into ST48, ST14 and ST348 respectively. Based on gyrA
      PCR- RFLP phylogenetic analysis all isolates were grouped as KpI. The predominant
      ESBL allele detected was blaCTX-M-15 which was found in 76% of isolates, followed
      by blaTEM-104 (19%), blaSHV-11 (3.2%) and blaTEM-176 (2%). The blaCTX-M-15 gene
      was located in multiple conjugative IncF plasmids ranging from 25 kb-485 kb in
      size. CONCLUSION: The high prevalence of blaCTX-M-15 observed among ESBL
      producing K. pneumoniae in Tanzania, is possibly due to the spread of a common
      IncFII 145 kb plasmid and of certain clones such as ST14 and ST48. Furthermore
      the 485 kb plasmid detected is the largest plasmid reported to carry blaCTX-M-15
      todate.

PMID- 24099284
TI  - Proteomic studies of isolated lipid droplets from bacteria, C. elegans, and
      mammals.
AB  - Lipid droplets (LDs) are an intracellular organelle, consisting of a neutral
      lipid core covered by a monolayer of phospholipids and proteins. It primarily
      mediates lipid storage, metabolism, and transportation. Recently, research of LDs
      has emerged as a rapidly developing field due to the strong linkage between
      ectopic lipid accumulation and metabolic syndromes. Recently, more than 30
      proteomic studies of isolated LDs have identified many important LD proteins that
      have highlighted and have also predicted the potential biological roles of the
      organelle, motivating the field to develop quite rapidly. This chapter summarizes
      methods used in proteomic studies for three representative species reported and
      discusses their advantages and disadvantages. We believe that this chapter
      provides useful information and methods for future LD proteomic studies
      especially for LDs in other species. 

PMID- 24099285
TI  - Analysis of yeast lipid droplet proteome and lipidome.
AB  - Lipid droplets (LD) are in the spotlight of lipid research because of the link of
      lipid storage to health and disease and the just incipient understanding of their
      involvement in cellular processes apart from nonpolar lipid metabolism. Yeast is
      an excellent model organism to study the lipidome and proteome of LD under
      different environmental conditions and to address new aspects of LD biology and
      chemistry. In this chapter, we describe a versatile protocol for the isolation of
      LD at high purity and address specific demands for handling different yeast
      species. Moreover, we discuss the analysis of the LD proteome and lipidome based
      on standard methods such as thin layer chromatography (TLC), gas liquid
      chromatography (GLC), mass spectrometry (MS) as well as GLC/MS. Finally, we point
      out similarities and disparities of LD proteome and lipidome from the three
      different yeasts Saccharomyces cerevisiae, Yarrowia lipolytica, and Pichia
      pastoris. 

PMID- 24099286
TI  - Visualization of lipid droplets in C. elegans by light and electron microscopy.
AB  - The powerful forward and reverse genetic tools, and emerging sets of biochemical
      assays for fat metabolites, make Caenorhabditis elegans an attractive model
      organism for elucidating conserved mechanisms in fat storage. The ability to
      observe lipid droplets in live animals at single cell resolution offers a unique
      advantage for studying cellular fat storage in vivo. In this chapter, we describe
      transgenic technologies for expressing fluorescent lipid droplet marker proteins
      at near-physiological levels. Methods to visualize these markers using sensitive
      confocal microscopy systems are detailed. Additional methods for visualizing
      lipid droplets by transmission electron microscopy and detection of lipid droplet
      associated proteins by immunoelectron microscopy are described. 

PMID- 24099287
TI  - Analysis of lipid droplet dynamics and functions in Drosophila melanogaster.
AB  - The lipid droplet (LD) is a unique cellular organelle containing a neutral-lipid
      core enclosed by a phospholipid monolayer and associated proteins. Despite the
      important function of LDs at the hub of cellular energy homeostasis regulation,
      major questions in the field of LD biology are still unanswered. Drosophila
      melanogaster has been used as a model organism to make fundamental discoveries in
      biology for over a century. In recent years, genome-wide unbiased reverse genetic
      screens using Drosophila cells or transgenic lines have been proven to provide
      valuable knowledge to the field of LD biology. Here we summarize the methods we
      use for functional genomic screens in Drosophila S2 cells to identify genes
      involved in LD biology, and the methods used for studying LD function in vivo
      using Drosophila as a model to combat metabolic diseases. 

PMID- 24099288
TI  - Analysis of oil droplets in microalgae.
AB  - Microalgae are diverse groups of eukaryotic organisms capable of efficiently
      converting sunlight into chemical energy through photosynthesis with
      carbohydrates and oils as major storage products. Like other eukaryotes,
      microalgae store oils in dynamic subcellular organelles named oil droplets. In
      this chapter, we present a detailed description of basic procedures that can be
      followed for the isolation of mutants defective in oil droplet biogenesis and for
      the imaging and analysis of oil droplets in the model unicellular green alga
      Chlamydomonas reinhardtii. Several commonly used methods for isolating and
      purifying oil droplets in microalgae are discussed. 

PMID- 24099289
TI  - Studying lipolysis in adipocytes by combining siRNA knockdown and adenovirus
      mediated overexpression approaches.
AB  - 3T3-L1 adipocytes are widely used as a model system for studying hormone
      stimulated lipolysis. However, these cells were limited in their utility for gain
      and loss-of-function studies due to the low efficiency of their transfection
      with plasmid DNA or small interfering RNA (siRNA) oligos. In this chapter, we
      provide a review of two methods established for manipulation of protein
      expression in differentiated mature adipocytes. The use of electroporation allows
      a high-efficiency delivery of siRNA oligos and subsequent knockdown of specific
      gene expression. A centrifugation-assisted infection with recombinant adenovirus,
      on the other hand, enables robust overexpression of ectopic proteins. Most
      importantly, by combining siRNA electroporation with adenovirus infection,
      simultaneous manipulation of levels of two different proteins can be achieved in
      differentiated adipocytes. Through subsequent analyses of lipase activity in cell
      extracts and fatty acid or glycerol release from living cells, mutual
      interdependence between the two proteins in the context of basal and hormone
      stimulated adipocyte lipolysis can be evaluated. 

PMID- 24099290
TI  - Analysis of lipid droplets in hepatocytes.
AB  - The liver plays an important role in triacylglycerol (TG) metabolism. It can
      store large amounts of TG in cytosolic lipid droplets (CLDs), or it can package
      TG into very-low density lipoproteins (VLDL) that are secreted from the cell. TG
      packaged into VLDL is derived from TG stored within the endoplasmic reticulum in
      lumenal lipid droplets (LLDs). Therefore, the liver contains at least three kinds
      of LDs that differ in their protein composition, subcellular localization, and
      function. Hepatic LDs undergo tremendous changes in their size and protein
      composition depending on the energetic (fasting/feeding) and pathological (viral
      infection, nonalcoholic fatty liver disease, etc.) states. It is crucial to
      develop methodologies that allow the isolation and analyses of the various
      hepatic LDs in order to gain insight into the differential metabolism of these
      important lipid storage/transport particles in health and disease. Here, we
      present detailed protocols for the isolation and analysis of CLDs and LLDs and
      for monitoring CLD dynamics. 

PMID- 24099291
TI  - Analysis of lipid droplets in cardiac muscle.
AB  - Cellular energy homeostasis is a crucial function of oxidative tissues but
      becomes altered with obesity, a major health problem that is rising unabated and
      demands attention. Maintaining cardiac lipid homeostasis relies on complex
      processes and pathways that require concerted actions between lipid droplets
      (LDs) and mitochondria to prevent intracellular accumulation of bioactive or
      toxic lipids while providing an efficient supply of lipid for conversion into
      ATP. While cardiac mitochondria have been extensively studied, cardiac LDs and
      their role in heart function have not been fully characterized. The cardiac LD
      compartment is highly dynamic and individual LD is small, making their study
      challenging. Here, we describe a simple procedure to isolate cardiac LDs that
      provide sufficient amounts of highly enriched material to allow subsequent
      protein and lipid biochemical characterization. We also present a detailed
      protocol to image cardiac LDs by conventional transmission electronic microscopy
      to provide two-dimensional (2D) analyses of cardiac LDs and mitochondria.
      Finally, we discuss the potential advantages of dual ion beam and electron beam
      platform (FIB-SEM) technology to study the cardiac LDs and mitochondria by
      allowing 3D imaging analysis. 

PMID- 24099292
TI  - Imaging cytoplasmic lipid droplets in enterocytes and assessing dietary fat
      absorption.
AB  - The primary function of the small intestine is digesting and absorbing nutrients
      from consumed food. Because of this, the small intestine is often thought of as a
      nutrient thoroughfare-enterocytes taking up nutrients on the apical side and then
      secreting nutrients from the basolateral side. The small intestine is not
      commonly thought of as a lipid storage organ; however, when meals and diets
      containing high amounts of fat are consumed, some dietary fat is stored in
      cytoplasmic lipid droplets (CLDs). The balance between storage and secretion of
      dietary fat by enterocytes is important in determining the physiological fate of
      dietary fat, including regulating blood lipid concentrations and energy balance.
      The existence of CLDs within enterocytes has likely evolved for three important
      physiological functions: (i) to allow the small intestine to efficiently absorb
      large amounts of energy dense fat, (ii) to control the rate of dietary fat
      entering circulation, and (iii) to alleviate lipotoxicity to enterocytes induced
      by high concentrations of free fatty acids, especially when a high fat meal is
      consumed. The purpose of this chapter is to provide methods for imaging CLDs in
      enterocytes and assessing different aspects of dietary fat absorption. 

PMID- 24099293
TI  - Lipid droplets and viral infections.
AB  - The lifecycle of several viruses is intimately tied to the lipid metabolism of
      their host cells, and lipid droplets (LDs) have emerged as crucial organelles in
      the propagation of these viral infections. Investigating the roles of LDs in
      viral infection requires expertise in both virology and cell metabolism
      pertaining to LDs. In this review, we offer an updated list and review of the
      multiples methods we have used in our laboratory to study both the role of LDs in
      viral infection and the effect of viral infection on cellular LDs, with a special
      emphasis on hepatitis C virus and other RNA viruses. 

PMID- 24099294
TI  - Purification of integral membrane proteins and lipid-binding assays.
AB  - The lipid droplet (LD) is an evolutionarily conserved organelle composed
      primarily of triglycerides (TAG) and cholesteryl esters. Recently, Fat storage
      Inducing Transmembrane proteins 1 & 2 (FITM1/FIT1 and FITM2/FIT2) were discovered
      as a conserved family of proteins involved in fat storage. FIT1 and FIT2 are both
      localized to the endoplasmic reticulum, but have distinct tissue distributions.
      FIT proteins mediate TAG LD accumulation when overexpressed, but do not
      synthesize TAG. FIT proteins function by partitioning newly synthesized TAG into
      LDs. In order to understand the mechanism by which this occurs, a method was
      developed to purify FIT proteins from insect cells in detergent micelles. The
      ability of purified FIT proteins to bind TAG and other neutral lipids was tested
      in detergent micelles, demonstrating lipid specificity and saturation binding.
      These techniques can be applied to a variety of proteins in lipid biology in an
      effort to try to reconstitute a mechanism of action or protein activity. The
      methods that will be discussed here can also be scaled to either screen a library
      of mutant proteins for binding to a particular compound or utilized to delineate
      structural requirements of ligands that are important for protein-ligand
      interactions. Here, we present a detailed description of the purification
      protocol and micellar protein-ligand binding experiments and their possible
      applications. 

PMID- 24099295
TI  - Imaging of neutral lipids and neutral lipid associated proteins.
AB  - Intracellular fat droplets are large and have a distinct morphology, which makes
      their imaging at the light level simple and informative. We detail how to image
      the fat droplet core by metabolic labeling with fluorescent fatty acids or
      lipophilic fluorochromes. Further, we describe the use of indirect immunostaining
      to image fat droplet proteins and fat cores in the same field. We also address
      the use of appropriate controls for determining signal specificity and other
      practical considerations for optimizing image quality. 

PMID- 24099296
TI  - Imaging lipid droplets by electron microscopy.
AB  - The lipid droplet (LD) is different from other cellular organelles in that most
      of its volume is made of lipid esters and its surface is lined by a phospholipid
      monolayer. This uniquely lipid-dominant structure poses a problem for electron
      microscopy (EM) because the aldehydes commonly used as a fixative do not react
      with most lipids. To circumvent this difficulty and utilize the high resolving
      power of EM, many methods have been developed. In this chapter, we discuss
      methods that have been used and/or are potentially useful to study LDs. The
      methods include conventional EM to observe the LD core, cryoelectron microscopy
      to observe the LD surface, freeze-substitution, immunoelectron microscopy (pre
      embedding, post-embedding, and cryosectioning methods), and freeze-fracture. Each
      method has strong and weak points and therefore some caution is necessary in
      interpreting the obtained results. In combination with methods of other
      disciplines, the electron microscopic techniques should contribute significantly
      to solving the remaining questions on LDs. 

PMID- 24099297
TI  - Imaging lipid droplet fusion and growth.
AB  - Lipid droplets (LDs) are highly dynamic cellular organelles found in most
      eukaryotic cell types. In white adipocytes, LDs grow into a characteristic
      unilocular morphology that is well suited for its specialized role as an
      efficient energy storage organelle. Overexpansion of LDs in white adipocytes
      results in the development of obesity and insulin resistance. Besides its central
      role in lipid storage and mobilization, LDs play crucial roles in various
      cellular processes including virus packaging, host defense, protein storage, and
      degradation. CIDE proteins, in particular Fsp27, initiates a unique LD fusion
      process in adipocytes by clustering and enriching at LD contact site and
      promoting neutral lipid exchange and transfer between contacted LDs. Here, we
      summarize our approaches to quantitatively measure intracellular LD size and
      neutral lipid exchange between LDs. Utilization of these methods has greatly
      facilitated our understanding of molecular pathways governing LD growth in
      adipocytes. 

PMID- 24099298
TI  - LDs comprise a hydrophobic, neutral lipid core.

PMID- 24099299
TI  - Regulation of Th17 maturation by interleukin 4.
AB  - Regulation of immune responses and control of autoimmunity depend on layers of
      checkpoints, cell-cell interactions, and soluble mediators, both during
      lymphocyte development and in the course of immune responses. With the definition
      and study of multiple distinct T-cell subsets, it is now apparent that, while
      specialized regulatory T cells (Tregs) have essential roles in immune
      homeostasis, important regulatory interactions also occur between the known
      effector Th subsets such as Th1, Th2 and Th17. In this review, we discuss the
      regulatory effects of the Th2 cell cytokine interleukin 4 (IL-4) on Th17 cell
      function, and we highlight emerging data, which indicate the importance of this
      interaction in both animal model systems and human disease.

PMID- 24099301
TI  - Infectious tolerance as candidate therapy for type 1 diabetes: transfer of
      immunoregulatory properties from human regulatory T cells to other T cells and
      proinflammatory dendritic cells.
AB  - Type 1 diabetes is a T-cell-mediated autoimmune disease in which the insulin
      producing cells in the islets of Langerhans are selectively destroyed. Although
      symptomatic insulin therapy is able to control glucose levels in the blood, many
      patients do not obtain the desired glycemic control, which increases the risk of
      diabetic complications. While many immunotherapeutic efforts to intervene in the
      disease process focus on systemic immune-suppressive therapies, antigen-specific
      immune modulation represents an attractive alternative. Dendritic cells modulated
      with 1.25(OH)2 vitamin D3, and dexamethasone (tolerogenic DCs) loaded with islet
      antigens induce Ag-specific regulatory CD4 T cells (iaTregs), offering a tissue
      specific intervention therapy. iaTregs exert their function via linked
      suppression to diminish effector cells by modulating pro-inflammatory DCs to
      upregulate inhibitory receptors. In turn, these re-educated mature DCs induce IL
      10-producing cells from the naive T-cell pool. Thus, tolerogenic DCs transfer
      regulatory properties to pro-inflammatory DCs via iaTregs (i.e., infectious
      tolerance). In this review, we describe the current knowledge regarding
      regulatory mechanisms of these tolerogenic DCs and the Tregs that they induce,
      and we propose that cell therapy with human tolerogenic DCs provides new
      opportunities for immune intervention in patients with autoimmune diseases.

PMID- 24099300
TI  - Antigen-specific tolerance in immunotherapy of Th2-associated allergic diseases.
AB  - Allergic diseases are an increasing health concern, particularly in the developed
      world. The standard clinical approach to treatment of allergic disease focuses on
      allergen avoidance and symptom control but does little to address the underlying
      Th2 bias of disease. Specific immunotherapy (SIT) consisting of controlled
      administration of allergen, however, has been demonstrated to successfully induce
      desensitization and tolerance in an antigen-specific manner for a variety of Th2
      mediated diseases. This review focuses on the mechanisms by which current SIT
      approaches induce tolerance as well as discussing attempts to modify the safety
      and efficacy of SIT. These refinements focus on three major aspects of SIT: the
      route of antigen administration, modification of the antigen to remove allergenic
      epitopes and reduce adverse events and choice of adjuvant used to induce
      tolerance and/or immune deviation from Th2 to Th1 and regulatory T-cell (Treg)
      phenotypes. Synthesis of these recent developments in SIT provides considerable
      promise for more robust therapies with improved safety profiles to improve
      resolution of allergic disease and its associated costs. 

PMID- 24099303
TI  - Influence of gastrointestinal digestion and edible plant combination on oral
      bioavailability of triterpene saponins, using a biomimetic digestion and
      absorption system and determination by HPLC.
AB  - Saponins have many biological activities, but their overload could cause toxicity
      to the human body. Bionic gastrointestinal digestion and monolayer liposome
      extraction were used for oral bioavailability assessment of triterpene saponins
      (notoginsenoside R1, ginsenosides Rb1 and Rd1) in an edible herb (San-Chi) and
      its compound herbal medicine (Pien Tze Huang, PZH). The concentrations of
      affinity-monolayer liposome saponins in the chyme were determined by HPLC and
      used for oral bioavailability assessment. With the digestion of San-Chi and PZH
      from the stomach to the intestine, the release of saponins in their chyme was
      increased. The intestinal absorption ratios of N-R1, G-Rb1, G-Rd1, and total
      saponins from San-Chi were 86.57, 18.56, 73.30, and 40.20%, respectively, which
      were more than those from PZH (i.e., 19.56, 10.11, 30.11, and 16.08%). The oral
      bioavailability of saponins was controlled by saponin species, gastrointestinal
      digestion, and edible plants combination. 

PMID- 24099304
TI  - 4-Phenyl-3,4-dihydroquinolone derivatives from Aspergillus nidulans MA-143, an
      endophytic fungus isolated from the mangrove plant Rhizophora stylosa.
AB  - Six new 4-phenyl-3,4-dihydroquinolone derivatives (1-6) along with the related
      aflaquinolone A (7) were isolated and identified from the cultures of Aspergillus
      nidulans MA-143, an endophytic fungus obtained from the fresh leaves of the
      marine mangrove plant Rhizophora stylosa. Their structures including absolute
      configurations were determined by spectroscopic analysis and electronic circular
      dichroism experiments, and the structure of compound 1 was confirmed by single
      crystal X-ray crystallographic analysis. In bioscreening experiments, none of the
      isolated compounds showed potent antibacterial or cytotoxic activity. However,
      compounds 2, 3, and 7 exhibited lethality against brine shrimp (Artemia salina),
      with LD50 values of 7.1, 4.5, and 5.5 MUM, respectively. 

PMID- 24099305
TI  - The BRICHOS domain, amyloid fibril formation, and their relationship.
AB  - Amyloid diseases are defined by tissue deposition of insoluble, fibrillar beta
      sheet polymers of specific proteins, but it appears that toxic oligomeric species
      rather than the fibrils are the main cause of tissue degeneration. Many proteins
      can form amyloid-like fibrils in vitro, but only ~30 proteins have been found to
      cause mammalian amyloid disease, suggesting that physiological mechanisms that
      protect against amyloid formation exist. The transmembrane region of lung
      surfactant protein C precursor (proSP-C) forms amyloid-like fibrils in vitro, and
      SP-C amyloid has been found in lung tissue from patients with interstitial lung
      disease (ILD). ProSP-C contains a BRICHOS domain, in which many ILD-associated
      mutations are localized, and the BRICHOS domain can prevent SP-C from forming
      amyloid-like fibrils. Recent data suggest that recombinant BRICHOS domains from
      proSP-C and Bri2 (associated with familial dementia and amyloid formation)
      interact with peptides with a strong propensity to form beta-sheet structures,
      including amyloid beta-peptide associated with Alzheimer's disease. Such
      interactions efficiently delay formation of fibrils and oligomers. The BRICHOS
      domain is defined at the sequence level and is found in ~10 distantly related
      proprotein families. These have widely different or unknown functions, but
      several of the proteins are associated with human disease. Structural modeling of
      various BRICHOS domains, based on the X-ray structure of the proSP-C BRICHOS
      domain, identifies a conserved region that is structurally complementary to the
      beta-sheet- and/or amyloid-prone regions in the BRICHOS domain-containing
      proproteins. These observations make the BRICHOS domain the first example of a
      chaperone-like domain with specificity for beta-prone regions.

PMID- 24099306
TI  - Ce(III) doped Zr-based MOFs as excellent NO2 adsorbents at ambient conditions.
AB  - New hybrid cerium modified zirconium based metal-organic frameworks (MOFs) were
      synthesized. The as-received materials were evaluated as adsorbents of NO2 in
      either moist or dry conditions. The surface of the initial and exhausted samples
      was characterized using XRD, SEM-EDX, nitrogen adsorption, thermal analysis, and
      FTIR. It was found that the addition of Ce(+3) slightly affects the growth of the
      framework and introduces new features to Zr-MOF. The shapes of the octahedral
      crystals are changed, and they are interwoven with rod-flake-like sheets. The
      extent of the interconnection, and thus the extent of the hybrid MOF formation,
      depends on the Zr to Ce ratio. The alterations in the surface chemistry and
      texture are reflected in the amount of NO2 adsorbed. The narrow pore channels
      present in these new materials enhance adsorption in either moist or dry
      conditions. The amount of NO2 adsorbed on the Ce-doped MOF increases over 25% in
      dry conditions in comparison with the unmodified MOF. Exposure of Ce-UiO-66 to
      NO2 results in a development of porosity. Regardless the conditions, the XRD
      patterns indicate the stability of this new hybrid MOF upon NO2 adsorption.
      Interactions of NO2 with MOF result in the formation of nitrate and nitrite
      species associated either with metals or with organic ligands. 

PMID- 24099302
TI  - MicroRNA regulation of T-lymphocyte immunity: modulation of molecular networks
      responsible for T-cell activation, differentiation, and development.
AB  - MicroRNAs (miRNA) are a class of small non-coding RNAs that constitute an
      essential and evolutionarily conserved mechanism for post-transcriptional gene
      regulation. Multiple miRNAs have been described to play key roles in T-lymphocyte
      development, differentiation, and function. In this review, we highlight the
      current literature regarding the differential expression of miRNAs in various
      models of murine and human T-cell biology. We emphasize mechanistic
      understandings of miRNA regulation of thymocyte development, T-cell activation,
      and differentiation into effector and memory subsets. We describe the
      participation of miRNAs in complex regulatory circuits shaping T-cell proteomes
      in a context-dependent manner. It is striking that some miRNAs regulate multiple
      processes, while others only appear in limited functional contexts. It is also
      evident that the expression and function of specific miRNAs can differ between
      murine and human systems. Ultimately, it is not always correct to simplify the
      complex events of T-cell biology into a model driven by only one or two master
      regulator miRNAs. In reality, T-cell activation and differentiation involve the
      expression of multiple miRNAs with many mRNA targets; thus, the true extent of
      miRNA regulation of T-cell biology is likely far more vast than currently
      appreciated. 

PMID- 24099307
TI  - Promising biomarkers for systemic lupus erythematosus.
AB  - INTRODUCTION: Systemic lupus erythematosus (SLE) is a systemic autoimmune disease
      with heterogeneous manifestations. Of particular importance for clinicians are
      the precise assessment of disease activity and the ability to make appropriate
      therapeutic decisions. Therefore, interest has increased in biomarkers that can
      be measured as indicators of pathogenic processes, disease activity and response
      to management. AREAS COVERED: This article introduces well-studied, as well as
      newly discovered, biomarkers related to SLE, divided into categories for
      diagnosis, disease activity and organ involvement. EXPERT OPINION: The lack of
      reliable biomarkers for lupus hampers the assessment of disease activity and
      impedes the evaluation of treatment response. Although many reports of lupus
      biomarkers have been published, few longitudinal and interventional studies have
      validated the utility of any biomarker for monitoring disease activity.
      Consortiums of investigators will certainly help in recruiting sufficient number
      of patients and facilitating the development of standardized assays. Moreover,
      owing to the multifactorial nature of lupus, a multiplexed approach will clearly
      be essential. Another promising approach is the use of high-throughput
      technology, including DNA and antibody microarrays, flow cytometry and proteomic
      techniques.

PMID- 24099308
TI  - HHV-6 antigen and HHV-6 DNA expression in sporadic adenomatous polyps of the
      colon.
AB  - BACKGROUND. Human herpesvirus-6B (HHV-6B) antigens are commonly found in the
      intestinal mucosa of patients with immunosuppression. In a series of
      immunocompetent patients with adenomatous, polyp HHV-6B antigen expression from
      mucosal biopsies was more intense than in biopsies taken from patients receiving
      immunosuppressive drugs because of kidney transplantation or inflammatory bowel
      disease. METHODS. HHV-6B and cytomegalovirus (CMV) antigen expression was
      determined from mucosal biopsy samples by immunohistochemistry. HHV-6-DNA content
      was studied in adenomatous polyps (seven tubular adenomas and one tubulovillous
      adenoma) taken from eight immunocompetent patients and in three mucosal biopsy
      samples taken from immunocompetent patients without adenomas using in situ
      hybridization (ISH) method. RESULTS. HHV-6B antigen expression on mucosal
      biopsies was strongly positive in five of eight patients with adenomas and
      negative in all patients without adenoma. CMV antigen expression on mucosal
      biopsies was faintly positive in three of adenoma patients. HHV-6 ISH was
      positive in seven of eight adenomatous polyps, most intense in the tubulovillous
      adenoma and negative in all three mucosal biopsies of patients without adenomas.
      CONCLUSION. Intensive HHV-6-DNA expression was found in adenomatous polyps of the
      colon. Further studies on involvement of HHV-6 in the development of
      gastrointestinal polyps are warranted.

PMID- 24099311
TI  - HIV vulnerabilities and coercive sex at same-sex sexual debut among men who have
      sex with men in Beijing, China.
AB  - Few studies have examined coercive sex and HIV vulnerabilities among men who have
      sex with men (MSM) in China. The present study seeks to compare individual
      characteristics between MSM who did and did not experience coercive sex at their
      MSM sexual debut and to identify HIV risk factors correlated with coercive sex at
      MSM sexual debut. In 2007, we recruited 167 MSM in Beijing, China by peer
      referred social network sampling. Each participant then completed self
      administered questionnaires regarding their sexual experiences and practices.
      Results show that 14% of participants reported coercive sex at MSM sexual debut,
      of whom 48% reported recent unprotected anal intercourse (UAI). Coercive sex at
      MSM sexual debut was significantly associated with UAI [adjusted odds ratio
      (AOR): 5.38, 95% confidence interval: 1.95-14.87] and lifetime number of male sex
      partners (AOR: 7.25, 95% CI: 2.39-22.01). Coercive sex is harming MSM in China
      and should be immediately addressed by researchers, public health officials, and
      MSM community stakeholders.

PMID- 24099312
TI  - Mercury biomagnification through food webs is affected by physical and chemical
      characteristics of lakes.
AB  - Mercury (Hg) contamination in aquatic systems remains a global concern because
      the organic form, methyl Hg (MeHg), can biomagnify to harmful concentrations in
      fish, fish-eating wildlife, and humans. Food web transfer of MeHg has been
      explored using models of log MeHg versus relative trophic position (nitrogen
      isotopes, delta(15)N), but regression slopes vary across systems for unknown
      reasons. In this study, MeHg biomagnification was determined for 11 lake food
      webs in Kejimkujik National Park, Nova Scotia, Canada, and compared to physical
      and chemical lake characteristics using principal component and multiple
      regression analyses. MeHg biomagnification (regression slopes of log MeHg versus
      baseline-adjusted delta(15)N for fishes and invertebrates) varied significantly
      across lakes and was higher in systems with lower aqueous nutrient/MeHg/chloride
      scores. This is one of the largest, consistent data sets available on MeHg
      biomagnification through temperate lake food webs and the first study to use a
      principal component and multiple regression approach to understand how lake
      chemical and physical characteristics interact to affect biomagnification among
      systems. Overall, our results show that the magnitude of MeHg biomagnification
      through lake food webs is related to the chemical and physical characteristics of
      the systems, but the underlying mechanisms warrant further investigation. 

PMID- 24099314
TI  - The impact of nurse working hours on patient safety culture: a cross-national
      survey including Japan, the United States and Chinese Taiwan using the Hospital
      Survey on Patient Safety Culture.
AB  - BACKGROUND: A positive patient safety culture (PSC) is one of the most critical
      components to improve healthcare quality and safety. The Hospital Survey on
      Patient Safety Culture (HSOPS), developed by the US Agency for Healthcare
      Research and Quality, has been used to assess PSC in 31 countries. However,
      little is known about the impact of nurse working hours on PSC. We hypothesized
      that long nurse working hours would deteriorate PSC, and that the deterioration
      patterns would vary between countries. Moreover, the common trends observed in
      Japan, the US and Chinese Taiwan may be useful to improve PSC in other countries.
      The purpose of this study was to clarify the impact of long nurse working hours
      on PSC in Japan, the US, and Chinese Taiwan using HSOPS. METHODS: The HSOPS
      questionnaire measures 12 sub-dimensions of PSC, with higher scores indicating a
      more positive PSC. Odds ratios (ORs) were calculated using a generalized linear
      mixed model to evaluate the impact of working hours on PSC outcome measures
      (patient safety grade and number of events reported). Tukey's test and Cohen's d
      values were used to verify the relationships between nurse working hours and the
      12 sub-dimensions of PSC. RESULTS: Nurses working >=60 h/week in Japan and the US
      had a significantly lower OR for patient safety grade than those working <40
      h/week. In the three countries, nurses working >=40 h/week had a significantly
      higher OR for the number of events reported. The mean score on 'staffing' was
      significantly lower in the >=60-h group than in the <40-h group in all the three
      countries. The mean score for 'teamwork within units' was significantly lower in
      the >=60-h group than in the <40-h group in Japan and Chinese Taiwan.
      CONCLUSIONS: Patient safety grade deteriorated and the number of events reported
      increased with long working hours. Among the 12 sub-dimensions of PSC, long
      working hours had an impact on 'staffing' and 'teamwork within units' in Japan,
      the US and Chinese Taiwan.

PMID- 24099315
TI  - Effectiveness of a self-management program for dual sensory impaired seniors in
      aged care settings: study protocol for a cluster randomized controlled trial.
AB  - BACKGROUND: Five to 25 percent of residents in aged care settings have a combined
      hearing and visual sensory impairment. Usual care is generally restricted to
      single sensory impairment, neglecting the consequences of dual sensory impairment
      on social participation and autonomy. The aim of this study is to evaluate the
      effectiveness of a self-management program for seniors who acquired dual sensory
      impairment at old age. METHODS/DESIGN: In a cluster randomized, single-blind
      controlled trial, with aged care settings as the unit of randomization, the
      effectiveness of a self-management program will be compared to usual care. A
      minimum of 14 and maximum of 20 settings will be randomized to either the
      intervention cluster or the control cluster, aiming to include a total of 132
      seniors with dual sensory impairment. Each senior will be linked to a licensed
      practical nurse working at the setting. During a five to six month intervention
      period, nurses at the intervention clusters will be trained in a self-management
      program to support and empower seniors to use self-management strategies. In two
      separate diaries, nurses keep track of the interviews with the seniors and their
      reflections on their own learning process. Nurses of the control clusters offer
      care as usual. At senior level, the primary outcome is the social participation
      of the seniors measured using the Hearing Handicap Questionnaire and the Activity
      Card Sort, and secondary outcomes are mood, autonomy and quality of life. At
      nurse level, the outcome is job satisfaction. Effectiveness will be evaluated
      using linear mixed model analysis. DISCUSSION: The results of this study will
      provide evidence for the effectiveness of the Self-Management Program for seniors
      with dual sensory impairment living in aged care settings. The findings are
      expected to contribute to the knowledge on the program's potential to enhance
      social participation and autonomy of the seniors, as well as increasing the job
      satisfaction of the licensed practical nurses. Furthermore, an extensive process
      evaluation will take place which will offer insight in the quality and
      feasibility of the sampling and intervention process. If it is shown to be
      effective and feasible, this Self-Management Program could be widely
      disseminated. CLINICAL TRIALS REGISTRATION: ClinicalTrials.gov, NCT01217502.

PMID- 24099316
TI  - Re-growth of an incomplete discoid lateral meniscus after arthroscopic partial
      resection in an 11 year-old boy: a case report.
AB  - BACKGROUND: Discoid lateral meniscus is common in children. Arthroscopic partial
      resection is indicated in symptomatic cases generally achieving satisfactory
      results. CASE PRESENTATION: We present a case of an incomplete discoid lateral
      meniscus of the right knee in an 11 year-old boy, treated with arthroscopic
      partial resection, which developed a re-growth of the remnant, restoring the pre
      operative incomplete discoid shape. To the best of our knowledge this is the
      first report about re-growth of a discoid meniscus after surgery. Debate still
      exists regarding the etiology of a discoid meniscus. Some authors proposed it is
      the persistence of the normal stage during fetal development. However, most other
      authors believe it is anomalous and arises through variant morphogenesis. The re
      growth of the discoid lateral meniscus following surgery in this patient seems to
      prove this latter theory. The residual growth of the knee involves also the
      lateral meniscus and that may have contributed to restoring the meniscus to the
      previous condition. CONCLUSION: This case report demonstrates discoid meniscal re
      growth in a child. The growth spurt may have an impact on meniscal regeneration.
      Re-growth of the discoid lateral meniscus in our patient favors the hypothesis of
      variant morphogenesis.

PMID- 24099318
TI  - FFM description of the triarchic conceptualization of psychopathy in men and
      women.
AB  - This study examined differential associations between phenotypic domains of the
      triarchic conceptualization of psychopathy (boldness, meanness, and
      disinhibition; Patrick, Fowles, & Krueger, 2009), as assessed by the Triarchic
      Psychopathy Measure (Patrick, 2010b), and the five-factor model (FFM) of normal
      personality, as indexed by the Revised NEO Personality Inventory (Costa & McCrae,
      1992; Spanish version, Costa & McCrae, 1999), in 349 undergraduates (96 men).
      Distinctive patterns of correlations for psychopathy components did not differ
      significantly across gender, although relations between Meanness and
      Agreeableness were stronger for men than for women. Our findings are largely
      consistent with the conceptualization of psychopathy in terms of FFM constructs
      and provide discriminant evidence in support of all 3 triarchic domains. Thus,
      meanness is marked by low Agreeableness and some degree of low Conscientiousness,
      whereas disinhibition is characterized both by low Conscientiousness and low
      Agreeableness along with high Neuroticism and Extraversion. Notably, the
      constellation of low Neuroticism, high Extraversion, and high Openness, with
      facets of low Agreeableness, supports the idea that boldness encompasses some
      adaptive features of psychological adjustment while depicting the interpersonal
      features of psychopathy.

PMID- 24099317
TI  - Polymorphisms in xenobiotic metabolizing genes, intakes of heterocyclic amines
      and red meat, and postmenopausal breast cancer.
AB  - Heterocyclic amines (HCAs) are mutagenic compounds generated when meats are
      cooked at high temperature and for long duration. The findings from previous
      studies on the relation between HCAs and breast cancer are inconsistent, possibly
      because of genetic variations in the enzymes metabolizing HCAs. To evaluate
      whether the associations of intakes of estimated HCAs, meat-derived mutagenicity
      (MDM), and red meat with risk of postmenopausal breast cancer were modified by N
      acetyltransferase 2 (NAT2) acetylator genotype or cytochrome P450 1A2-164 A/C
      (CYP1A2) polymorphism, we conducted a nested case-control study with 579 cases
      and 981 controls within a prospective cohort, the Nurses' Health Study. HCAs and
      MDM intakes were derived using a cooking method questionnaire administered in
      1996. NAT2acetylator genotype, the CYP1A2 polymorphism, and intakes of HCAs, MDM,
      and red meat were not associated with risk of postmenopausal breast cancer. There
      was also no interaction between NAT2 acetylator genotype or CYP1A2 polymorphism
      and HCAs and MDM and red meat intake in relation to breast cancer. These results
      do not support the hypothesis that genetic polymorphisms of xenobiotic enzymes
      involved in the metabolism of HCAs may modify the associations between intakes of
      red meat or meat-related mutagens and breast cancer risk. 

PMID- 24099319
TI  - Investigating citrullinated proteins in tumour cell lines.
AB  - BACKGROUND: The conversion of arginine into citrulline, termed citrullination,
      has important consequences for the structure and function of proteins. Studies
      have found PADI4, an enzyme performing citrullination, to be highly expressed in
      a variety of malignant tumours and have shown that PADI4 participates in the
      process of tumorigenesis. However, as citrullinated proteins have not been
      systematically investigated in tumours, the present study aimed to identify novel
      citrullinated proteins in tumours by 2-D western blotting (2-D WB). METHODS: Two
      identical two-dimensional electrophoresis (2-DE) gels were prepared using
      extracts from ECA, H292, HeLa, HEPG2, Lovo, MCF-7, PANC-1, SGC, and SKOV3 tumour
      cell lines. The expression profiles on a 2-DE gel were trans-blotted to PVDF
      membranes, and the blots were then probed with an anti-citrulline antibody. By
      comparing the 2-DE profile with the parallel 2-D WB profile at a global level,
      protein spots with immuno-signals were collected from the second 2-DE gel and
      identified using mass spectrometry. Immunoprecipitation was used to verify the
      expression and citrullination of the targeted proteins in tumour cell lines.
      RESULTS: 2-D WB and mass spectrometry identified citrullinated alpha-enolase
      (ENO1), heat shock protein 60 (HSP60), keratin 8 (KRT8), tubulin beta (TUBB), T
      cell receptor chain and vimentin in these cell lines. Immunoprecipitation
      analyses verified the expression and citrullination of ENO1, HSP60, KRT8, and
      TUBB in the total protein lysates of the tumour cell lines. CONCLUSIONS: The
      citrullination of these proteins suggests a new mechanism in the tumorigenic
      process.

PMID- 24099320
TI  - A quick and low-cost PCR-based assay for Candida spp. identification in positive
      blood culture bottles.
AB  - BACKGROUND: Differences in the susceptibility of Candida species to antifungal
      drugs make identification to the species level important for clinical management
      of candidemia. Molecular tests are not yet standardized or available in most
      clinical laboratories, although such tests can reduce the time required for
      species identification, as compared to the conventional culture-based methods. To
      decrease laboratory costs and improve diagnostic accuracy, different molecular
      methods have been proposed, including DNA extraction protocols to produce pure
      DNA free of PCR inhibitors. The objective of this study was to validate a new
      format of molecular method, based on the internal transcribed spacer (ITS) of the
      rDNA gene amplification followed by sequencing, to identify common and cryptic
      Candida species causing candidemia by analyzing DNA in blood culture bottles
      positive for yeasts. METHODS: For DNA extraction, an "in-house" protocol based on
      organic solvent extraction was tested. Additional steps of liquid nitrogen
      incubation followed by mechanical disruption ensured complete cell lysis, and
      highly pure DNA. One hundred sixty blood culture bottles positive for yeasts were
      processed. PCR assays amplified the ITS region. The DNA fragments of 152 samples
      were sequenced and these sequences were identified using the GenBank database
      (NCBI). Molecular yeast identification was compared to results attained by
      conventional method. RESULTS: The organic solvent extraction protocol showed high
      reproducibility in regards to DNA quantity, as well as high PCR sensitivity (10
      pg of C. albicans DNA and 95% amplification on PCR). The identification of
      species at the molecular level showed 97% concordance with the conventional
      culturing method. The molecular method tested in the present study also allowed
      identification of species not commonly implicated in human infections.
      CONCLUSIONS: This study demonstrated that our molecular method presents
      significant advantages over the conventional yeast culture identification method
      by providing accurate results within 24 hours, in contrast to at least 72 hours
      required by the automated conventional culture method. Additionally, our
      molecular method allowed the identification of mixed infections, as well as
      infections due to emergent fungal pathogens. This economical DNA extraction
      method developed in our laboratory provided high-quality DNA and 60% cost savings
      compared to commercial methods.

PMID- 24099322
TI  - On the morphology and taxonomy of Griphobilharzia amoena Platt and Blair, 1991
      (Schistosomatoidea), a dioecious digenetic trematode parasite of the freshwater
      crocodile, Crocodylus johnstoni, in Australia.
AB  - Griphobilharzia amoena Platt and Blair, 1991 was originally described as a
      dioecious trematode, parasitic in the circulatory system of the Australian
      freshwater crocodile, Crocodylus johnstoni, with the female completely enclosed
      in a gynecophoric chamber of the male and the 2 worms oriented anti-parallel to
      each other. A recent publication questions the original description, arguing that
      G. amoena is monoecious and, as a consequence, the species was transferred to
      Vasotrema Stunkard, 1928 (Spirorchiidae) as Vasotrema amoena n. comb. We provide
      photomicrographic evidence that the original description of G. amoena is correct
      and that Griphobilharzia Platt and Blair, 1991, is a valid monotypic genus
      containing G. amoena. An accurate understanding of the anatomy of G. amoena is
      not trivial and has implications for revealing the complex origins and evolution
      of the dioecious condition within the Schistosomatoidea.

PMID- 24099321
TI  - Role of fluorophore-metal interaction in photoinduced electron transfer (PET)
      sensors: time-dependent density functional theory (TDDFT) study.
AB  - The origins of fluorescence quenching by Hg(II) ion chelation and fluorescence
      enhancement by Zn(II) ion chelation to a PET sensor are investigated.
      Specifically, the fluorescence quenching and enhancing mechanisms associated with
      the ligand ADPA (N-(9-anthracenylmethyl)-N-(2-pyridinylmethyl)-2
      pyridinemethanamine), protonated ADPA and metal bound (Zn(II) and Hg(II)) ADPA
      are studied via density functional theory (DFT) and time-dependent DFT (TDDFT)
      methods. The study found that a structural change in the excited state of ADPA
      induces reordering of the frontier molecular orbitals, and the S1 -> S0
      transition becomes a charge transfer transition from the fluorophore to the
      tertiary nitrogen of the dipicolylamine (DPA) unit, which is forbidden.
      Protonation on the tertiary amine or chelation of Zn(II) prevents such changes,
      and the HOMO-LUMO transition is contained within the fluorophore. Therefore,
      fluorescence is restored. The chelation of Hg(II), on the other hand, promotes
      extensive interaction between the Hg(II) ion and the fluorophore, which is
      reflected in the short Hg(II)-fluorophore distance (3.11 A). A noticeable
      structural change upon the S0 -> S1 transition is observed in the Hg(II)-ADPA
      system as well, where the resulting S1 -> S0 transition becomes a charge transfer
      transition from mercury to the fluorophore and the fluorescence is thus quenched.
      Therefore, the present DFT/TDDFT calculations reproduce the fluorescence on-off
      behavior associated with the entire ADPA family of complexes, which illustrates
      that the combination of DFT and TDDFT calculations, including excited state
      geometry optimization, can be a valuable tool to uncover the detailed
      fluorescence sensing mechanisms. 

PMID- 24099324
TI  - Iron-catalyzed aerobic oxidation of allylic alcohols: the issue of C?C bond
      isomerization.
AB  - An aerobic oxidation of allylic alcohols using Fe(NO3)3.9H2O/TEMPO/NaCl as
      catalysts under atmospheric pressure of oxygen at room temperature was developed.
      This eco-friendly and mild protocol provides a convenient pathway to the
      synthesis of stereodefined alpha,beta-unsaturated enals or enones with the
      retention of the C-C double-bond configuration. 

PMID- 24099326
TI  - Stimuli-sensitive hydrogels: an excellent carrier for drug and cell delivery.
AB  - The stimuli-sensitive hydrogel is an injectable formulation that is used to
      deliver drugs, cells, and genes into the body. Hydrogels are available in various
      physical forms such as solid molded, pressed powder matrix, microparticle,
      coating, or membrane forms. The network structure of hydrogels can be
      macroporous, microporous, or nonporous. Different categories of biomaterials,
      such as natural, synthetic, and combinations (e.g., semisynthetic such as natural
      natural, natural-synthetic, and synthetic-synthetic polymers), are commonly used
      in hydrogel preparation. Classification of hydrogels mainly depends upon physical
      stimuli (temperature, electric fields, solvent composition, light, pressure,
      sound, and magnetic fields) and chemical or biochemical stimuli (pH, ions, and
      specific molecular recognition events). Several approaches for the synthesis of
      hydrogels have been reported, including emulsification, micromolding,
      photolithography, isostatic ultra high pressure, and microfluidic techniques.
      Hydrogels provide structural integrity and cellular organization, serve as tissue
      barriers, act as bioadhesive and drug depots, deliver bioactive agents and cells,
      and possess unique swelling properties and structures. This review provides a
      detailed account of the need for development of hydrogels, along with the
      materials used and techniques adopted to manufacture scaffolds for tissue
      engineering and for prolonged drug, cell, and gene delivery. 

PMID- 24099325
TI  - The presence and prognostic impact of apoptotic and nonapoptotic disseminated
      tumor cells in the bone marrow of primary breast cancer patients after
      neoadjuvant chemotherapy.
AB  - INTRODUCTION: Neoadjuvant systemic therapy of primary breast cancer (PBC)
      patients offers the possibility to monitor treatment response. However, patients
      might have metastatic relapse despite achieving a pathologic complete response
      (pCR). This indicates that local response to therapy must not be representative
      for systemic treatment efficacy. Therefore, the aim of this study was to compare
      local response with systemic tumor cell dissemination by determining the presence
      of disseminated tumor cells (DTCs), including apoptotic tumor cells, in the bone
      marrow (BM) of PBC patients after neoadjuvant chemotherapy (NACT). METHODS: DTCs
      were detected by immunocytochemistry (pancytokeratin antibody A45-B/B3) and
      cytomorphology (DTC status). The presence of apoptotic tumor cells was determined
      by using the M30 antibody (M30 status). This antibody detects a neo-epitope that
      is expressed only during early apoptosis. RESULTS: BM aspirates from 400 PBC
      patients that had completed NACT were eligible for this study. Of these, 167
      (42%) patients were DTC positive (DTC status). The M30 status was investigated in
      308 patients. Apoptotic (M30-positive) tumor cells were detected in 89 (29%) of
      these. Whereas the DTC status was not correlated (P = 0.557) to local treatment
      response (that is, pCR or a clinical complete/partial response), the presence of
      M30-positive tumor cells was significantly higher in patients that responded to
      therapy (P = 0.026). Additionally, DTC-positive patients were at an increased
      risk for disease relapse (hazard ratio, 1.87; 95% CI, 1.11 to 3.15; P = 0.019).
      CONCLUSION: The presence of DTC is independent of therapy response of the primary
      tumor. As patients that are DTC positive after NACT have an unfavorable outcome,
      they might benefit from additional systemic treatment.

PMID- 24099327
TI  - In situ gel-forming system: an attractive alternative for nasal drug delivery.
AB  - Intranasal delivery is one of the most interesting and challenging endeavors
      facing pharmaceutical scientists. The conventional nasal drug delivery systems
      including solutions, suspensions, and ointments show drawbacks such as short
      residence in the nasal cavity, highly variable efficiency, low permeability, and
      inconvenient administration. In situ gel-forming systems are an interesting
      polymeric system that exists as flowing aqueous solution before administration
      and undergoes phase transition to form a viscoelastic gel in a physiologic
      environment. Benefiting from the merits of both a solution and a gel, an
      impressive number of in situ gel-forming systems induced by temperature, pH, and
      ions have been prepared for use in nasal drug delivery in the past few years. In
      situ gel-forming systems increase the retention of drugs in the nasal cavity, and
      some of them also show permeation-enhancing capabilities. This article reviews
      the in situ gel-forming systems used for nasal drug delivery and introduces their
      gelling mechanisms and other favorable features for intranasal delivery. It also
      describes the release patterns and drug stability of in situ gels as well as
      their in vivo performances and local safety following nasal administration. 

PMID- 24099328
TI  - A pharmacokinetic overview of nanotechnology-based drug delivery systems: an ADME
      oriented approach.
AB  - With the extensive progress in nanotechnology-based drug delivery systems,
      pharmacokinetic evaluations have gained much attention from researchers as a
      central part of the study of these systems. Because the fulfillment of any
      therapeutic goal(s) by a novel drug delivery system requires that the absorption,
      distribution, metabolism, and excretion (ADME) be considered from the early
      stages of the system design to the final clinical evaluations, extensive
      knowledge of the pharmacokinetic aspects related to ADME is a crucial part of
      research in this field. The main objectives of the nanotechnology-based drug
      delivery systems from a pharmacokinetic viewpoint are (1) an improved drug
      release profile in vivo, (2) enhanced drug absorption, (3) site-directed drug
      distribution, (4) a modified drug metabolism pattern, (5) prolonged drug
      residence time in body (e.g., in blood circulation), and (6) delayed and/or
      decreased renal excretion of the drug. Accordingly, the purpose of the current
      review is to present an insightful summary of pharmacokinetic analyses of
      nanotechnology-based drug delivery systems along with a critical review of recent
      findings. 

PMID- 24099329
TI  - Mediastinal hydatid cyst: a case report.
AB  - INTRODUCTION: Mediastinal localization of hydatidosis is very rare even in
      endemic areas. The diagnosis is based on typical clinical and radiological
      criteria. CASE PRESENTATION: We report a case of a mediastinal location of
      hydatidosis in a 60-year-old Arab man admitted for chest pain. The chest
      radiograph showed a rounded and homogeneous opacity. Computed tomography showed a
      right mediastinal cyst, without other thoracic or abdominal sites. Through a
      posterolateral thoracotomy, we found a cystic mass in the posterior mediastinum.
      The patient received a cystectomy with medical treatment based on albendazole. He
      improved a few weeks later. CONCLUSION: Mediastinal cysts remain rare, even in
      endemic countries, which makes initial diagnosis difficult. Our observation shows
      the importance of keeping this diagnosis in mind when a patient presents with
      signs of mediastinal compression.

PMID- 24099331
TI  - Fidelity of RNA polymerase II transcription: Role of Rpb9 [corrected] in error
      detection and proofreading.
AB  - The role of the small RNA polymerase II subunit Rpb9 in transcriptional
      proofreading was assessed in vitro. Transcription elongation complexes in which
      the 3' end of the RNA is not complementary to the DNA template have a
      dramatically reduced rate of elongation, which provides a fidelity checkpoint at
      which the error can be removed. The efficiency of such proofreading depends on
      competing rates of error propagation (extending the RNA chain without removing
      the error) and error excision, a process that is facilitated by TFIIS. In the
      absence of Rpb9, the rate of error propagation is increased by 2- to 3-fold in
      numerous sequence contexts, compromising the efficiency of proofreading. In
      addition, the rate and extent of TFIIS-mediated error excision is also
      significantly compromised in the absence of Rpb9. In at least some sequence
      contexts, Rpb9 appears to enhance TFIIS-mediated error excision by facilitating
      efficient formation of a conformation necessary for RNA cleavage. If a
      transcription error is propagated by addition of a nucleotide to the mismatched
      3' end, then the rate of further elongation increases but remains much slower
      than that of a complex with a fully base-paired RNA, which provides a second
      potential fidelity checkpoint. The absence of Rpb9 also affects both error
      propagation and TFIIS-mediated error excision at this potential checkpoint in a
      manner that compromises transcriptional fidelity. In contrast, no effects of Rpb9
      on NTP selectivity were observed.

PMID- 24099330
TI  - Effect of neovestitol-vestitol containing Brazilian red propolis on accumulation
      of biofilm in vitro and development of dental caries in vivo.
AB  - The present study examined the influences of the neovestitol-vestitol (NV)
      containing fraction isolated from Brazilian red propolis on the development of
      biofilm and expression of virulence factors by Streptococcus mutans using saliva
      coated surfaces of hydroxyapatite. In addition, NV was tested in a rodent model
      of dental caries to assess its potential effectiveness in vivo. Topical
      applications of NV (800 MUg ml(-1)) significantly impaired the accumulation of
      biofilms of S. mutans by largely disrupting the synthesis of glucosyltransferase
      derived exopolysaccharides and the expression of genes associated with the
      adaptive stress response, such as copYAZ and sloA. Of even greater impact, NV was
      as effective as fluoride (positive control) in reducing the development of
      carious lesions in vivo. NV is a promising natural anti-biofilm agent that
      targets essential virulence traits in S. mutans, which are associated with the
      formation of cariogenic biofilm and the subsequent onset of dental caries
      disease. 

PMID- 24099332
TI  - A microbiological evaluation of level of disinfection for flexible cystoscopes
      protected by disposable endosheaths.
AB  - BACKGROUND: Flexible cystoscopy is used in urological outpatient departments for
      diagnostic cystoscopy of bladder cancer and requires a high-level disinfection
      between each patient. The purpose of this study was to make a microbiological
      post disinfection efficacy assessment of flexible cystoscopes (FC) using
      disposable sterile endosheaths. METHODS: One hundred endosheaths underwent a leak
      test for barrier integrity after cystoscopy. Microbiological samples from these
      cystoscopies were obtained; after removal of the endosheath, and after cleaning
      the scope with a detergent cloth, rinsing with tap water followed by 70% ethanol
      disinfection and subsequent drying. The number of colony forming units (cfu) from
      the samples was counted after 72 hours and then divided in three categories,
      Clean FC (<5 cfu/sample), Critical FC (5-50 cfu/sample) and High-risk FC (>50
      cfu/sample). The result was compared with data of 10 years continuous control
      sampling recorded in the Copenhagen Clean-Endoscope Quality Control Database
      (CCQCD) and analyzed with a Chi-square test for homogeneity. RESULTS: All 100
      endosheaths passed the leak-test. All samples showed a Clean FC and low means of
      cfu. A query to the CCQCD, showed that 99.8% (1264/1267) of all FC with a built
      in work-channel reprocessed in a WD were clean before use. CONCLUSION: The
      reprocessing of FC using endosheaths, as preformed in this study, provides a
      patient-ready procedure. The results display a reprocessing procedure with low
      risk of pathogen transmission, high patient safety and a valid alternative to the
      recommended high-level disinfection procedure of FC. However, the general
      impression was that sheaths slightly reduced vision and resulted in some patient
      discomfort.

PMID- 24099333
TI  - Oral lesions and pulmonary fibrosis after ingesting grapes.
AB  - A young rural man referred to us with profound icterus and dyspnea after he had
      eaten three grapes almost 10 days earlier. He had referred to a local hospital 30
      min after ingestion with nausea, vomiting and abdominal pain and was
      conservatively managed. He then became icteric and began to experience dyspnea
      and was referred to our center with an O(2) saturation of 77% and abnormal liver
      and renal function tests. Glossitis with a green-yellow pseudomembrane and
      subcutaneous emphysema were noticed. After detection of lung fibrosis in chest X
      ray, he was put on the antioxidant and immunosuppressive therapy, but expired
      almost 20 h after admission.

PMID- 24099334
TI  - Impact of telehealth on general practice contacts: findings from the whole
      systems demonstrator cluster randomised trial.
AB  - BACKGROUND: Telehealth is increasingly used in the care of people with long term
      conditions. Whilst many studies look at the impacts of the technology on hospital
      use, few look at how it changes contacts with primary care professionals. The aim
      of this paper was to assess the impacts of home-based telehealth interventions on
      general practice contacts. METHOD: Secondary analysis of data from a Department
      of Health funded cluster-randomised trial with 179 general practices in three
      areas of England randomly assigned to offer telehealth or usual care to eligible
      patients. Telehealth included remote exchange of vitals signs and symptoms data
      between patients and healthcare professionals as part of the continuing
      management of patients. Usual care reflected the range of services otherwise
      available in the sites, excluding telehealth. Anonymised data from GP systems
      were used to construct person level histories for control and intervention
      patients. We tested for differences in numbers of general practitioner and
      practice nurse contacts over twelve months and in the number of clinical readings
      recorded on general practice systems over twelve months. RESULTS: 3,230 people
      with diabetes, chronic obstructive pulmonary disease or heart failure were
      recruited in 2008 and 2009. 1219 intervention and 1098 control cases were
      available for analysis. No statistically significant differences were detected in
      the numbers of general practitioner or practice nurse contacts between
      intervention and control groups during the trial, or in the numbers of clinical
      readings recorded on the general practice systems. CONCLUSIONS: Telehealth did
      not appear associated with different levels of contact with general practitioners
      and practice nurses. We note that the way that telehealth impacts on primary care
      roles may be influenced by a number of other features in the health system. The
      challenge is to ensure that these systems lead to better integration of care than
      fragmentation. TRIAL REGISTRATION NUMBER: International Standard Randomised
      Controlled Trial Number Register ISRCTN43002091.

PMID- 24099335
TI  - Getting into the cilia: nature of the barrier(s).
AB  - The primary cilium that protrudes from the plasma membrane of many eukaryotic
      cell types is very much a cellular organelle in its own right. Its unique
      membrane and luminal composition is effectively compartmentalized by diffusion
      barrier at its base, known as the transition zone. Recent works have now shed
      light on the molecular components of this diffusion barrier, and revealed
      intriguing functional similarities with other better characterized cellular
      barriers.

PMID- 24099336
TI  - Glycophorin C ligation: another biochemical pathway in red blood cell senescence?

PMID- 24099337
TI  - New insights for preventing transfusion-transmitted cytomegalovirus and other
      white blood cell-associated viral infections.

PMID- 24099338
TI  - Bacterial testing of platelet components: is there added benefit for our donors?

PMID- 24099339
TI  - First "themed issue" of TRANSFUSION on thirty years of progress in blood safety
      since recognition of transfusion-associated AIDS.

PMID- 24099340
TI  - Transfusion medicine illustrated. Green plasma in female blood donors on estrogen
      containing birth control pills.

PMID- 24099342
TI  - Plasma transfusion volume and liver transplantation safety.

PMID- 24099343
TI  - Bond-selective dissociation of polyatomic cations in mid-infrared strong fields.
AB  - Strong field-induced dissociation by intense mid-infrared pulses was investigated
      in bromofluoroform monocation (CF3Br(+)) and iodobenzene dication (C6H5I(2+))
      using ab initio molecular dynamics calculations. In both systems, bond -selective
      dissociation was achieved using appropriate laser polarizations and wavelengths.
      For CF3Br(+), energetically disfavored fluorine elimination was strongly enhanced
      at wavelengths of 7 to 8 MUm with polarization along a C-F bond. This is the
      result of two effects: the deposition of high enough kinetic energy into the
      molecule by the laser field and the near-resonant excitation of the C-F
      stretching mode. At shorter and off-resonant wavelengths, bromine elimination
      becomes significant due to rapid intramolecular vibrational energy redistribution
      (IVR). For C6H5I(2+), the branching ratios for the dissociation of the ortho-,
      meta-, and para-hydrogens can be controlled simply by changing the laser
      polarization. These results show the general applicability of bond selective
      dissociation of cations by intense mid-infrared laser fields. 

PMID- 24099345
TI  - Efficacy and safety of thrice weekly DOTS in tuberculosis patients with and
      without HIV co-infection: an observational study.
AB  - BACKGROUND: Despite the latest World Health Organization guidelines advocating
      daily therapy in HIV-TB co-infected individuals, there are few recent studies
      comparing outcomes of thrice-weekly anti-tuberculosis treatment in HIV-positive
      and HIV-negative patients with TB. The present study sets out to compare TB
      treatment outcomes in these two groups in the Indian national programme, which
      currently involves thrice-weekly therapy for all, regardless of HIV status.
      METHODS: HIV-positive and HIV-negative were consecutively screened for enrolment
      into this prospective observational study, carried out at the All India Institute
      of Medical Sciences hospital, New Delhi, India, between 2006 and 2010. Patients
      were given short-course thrice-weekly rifampicin-based therapy, with all HIV
      positive patients being started on highly active antiretroviral therapy at least
      14 days after commencing TB treatment. Patients were regularly followed-up for 24
      months after completion of treatment. RESULTS: 150 HIV-positive, 155 HIV-negative
      patients were enrolled consecutively for the study. Significantly higher
      treatment success (93.5% vs. 76.7% at end of treatment, p < 0.001) and lower
      mortality (2.8% vs. 21.6% on follow up, p < 0.001) were observed in HIV-negative
      patients. No significant difference was found in treatment failure (p = 0.16),
      sputum smear (p = 0.58) and culture conversion (p = 0.55), and non-serious
      adverse event incidence (p = 0.851) between the two groups. Low baseline CD4 cell
      count (<100 cells/ mm3) was the only predictor of mortality in HIV-TB patients
      (odds ratio 8 . 43, p = 0 . 013). CONCLUSIONS: Thrice-weekly anti-tuberculosis
      therapy is more effective in HIV-negative than in HIV-positive patients. However,
      outcomes in this HIV co-infected cohort were found to be similar to those
      reported previously with daily therapy, with no safety concerns. This should
      prompt further study into whether intermittent or daily therapy should be used
      universally in resource-poor settings, using large well executed randomised
      controlled trials. TRIAL REGISTRATION: NCT No. 00698334.

PMID- 24099346
TI  - Statistical significance criteria for the rWG and average deviation interrater
      agreement indices.
AB  - Despite the widespread use of interrater agreement statistics for multilevel
      modeling and other types of research, the existing guidelines for inferring the
      statistical significance of interrater agreement are quite limited. They are
      largely relevant only under conditions that numerous researchers have argued
      rarely exist. Here we address this problem by generating guidelines for inferring
      statistical significance under a number of conditions via a computer simulation.
      As a set, these guidelines cover many of the conditions researchers commonly
      face. We discuss how researchers can use the guidelines presented to more
      reasonably infer the statistical significance of interrater agreement relative to
      using the limited guidelines available in the extant literature.

PMID- 24099347
TI  - Physiological mechanisms that underlie the effects of interactional unfairness on
      deviant behavior: the role of cortisol activity.
AB  - Although experiencing unfairness is a primary source of stress, there are
      surprisingly few studies that have examined the physiological underpinnings of
      unfairness. Drawing from social self-preservation theory, we derive predictions
      regarding the effects of interactional unfairness on activity in the hypothalamic
      pituitary-adrenocortical (HPA) axis, which is one of the body's primary hormonal
      systems for responding to stress. Using an experimental design with objective
      physiological measures, we found support for our hypothesis that interactional
      unfairness triggers the release of cortisol by the HPA axis. This cortisol
      activity in turn mediated the effects of interactional unfairness on deviant
      behavior. This indirect effect remained significant after controlling for
      established attitudinal and self-construal mediators of the justice-deviance
      relationship. We discuss the theoretical and practical implications of these
      findings for the occupational stress and organizational justice literatures.

PMID- 24099348
TI  - What I experienced yesterday is who I am today: relationship of work motivations
      and behaviors to within-individual variation in the five-factor model of
      personality.
AB  - Historically, organizational and personality psychologists have ignored within
      individual variation in personality across situations or have treated it as
      measurement error. However, we conducted a 10-day experience sampling study
      consistent with whole trait theory (Fleeson, 2012), which conceptualizes
      personality as a system of stable tendencies and patterns of intraindividual
      variation along the dimensions of the Big Five personality traits (Costa &
      McCrae, 1992). The study examined whether (a) internal events (i.e., motivation),
      performance episodes, and interpersonal experiences at work predict deviations
      from central tendencies in trait-relevant behavior, affect, and cognition (i.e.,
      state personality), and (b) there are individual differences in responsiveness to
      work experiences. Results revealed that personality at work exhibited both
      stability and variation within individuals. Trait measures predicted average
      levels of trait manifestation in daily behavior at work, whereas daily work
      experiences (i.e., organizational citizenship, interpersonal conflict, and
      motivation) predicted deviations from baseline tendencies. Additionally,
      correlations of neuroticism with standard deviations in the daily personality
      variables suggest that, although work experiences influence state personality,
      people higher in neuroticism exhibit higher levels of intraindividual variation
      in personality than do those who are more emotionally stable.

PMID- 24099349
TI  - A murine monoclonal antibody based enzyme-linked immunosorbent assay for almond
      (Prunus dulcis L.) detection.
AB  - A sandwich enzyme-linked immunosorbent assay (ELISA) using anti-almond soluble
      protein rabbit polyclonal antibodies as capture antibodies and murine monoclonal
      antibody 4C10 as the detection antibodies was developed. The assay is specific
      and sensitive (3-200 ng almond protein/mL) for almond detection. The standardized
      assay is accurate (<15% CV) and reproducible (intra- and inter assay variability
      <15% CV). The assay did not register any cross-reactivity with the tested food
      matrices, suggesting the assay to be almond amandin specific. The assay could
      detect the presence of declared almond in the tested matched commercial samples.
      Further, the assay reliably detected the presence of almonds in the laboratory
      prepared food samples spiked with almond flour. 

PMID- 24099350
TI  - Effects of Qishe Pill, a compound traditional Chinese herbal medicine, on
      cervical radiculopathy: study protocol for a randomized controlled trial.
AB  - BACKGROUND: Neck pain is a common symptom in most patients suffering from
      cervical radiculopathy. However, some conservative treatments are limited by
      their modest effectiveness. On the other hand, surgical intervention for cervical
      disc disorders is indicated when symptoms are refractory to conservative
      treatments and neurological symptoms are progressive. Many patients use
      complementary and alternative medicine, including traditional Chinese medicine,
      to address their symptoms. The purpose of the present study is to examine the
      efficacy and safety of Qishe Pill, a compound traditional Chinese herbal
      medicine, for neck pain in patients with cervical radiculopathy. METHODS/DESIGN:
      A multicenter, double-blind, randomized, placebo-controlled trial to evaluate the
      efficacy and safety of the Qishe Pill is proposed. The study will include 240
      patients from five sites across China and diagnosed with cervical radiculopathy,
      according to the following inclusion criteria: age 18 to 65 with pain or
      stiffness in the neck for at least 2 weeks (neck disability index score 25 or
      more) and accompanying arm pain that radiates distally from the elbow. Qualified
      participants will be randomly allocated into two groups: Qishe Pill group and
      placebo group. The prescription of the trial medications (Qishe Pill/placebo) are
      3.75 g each twice a day for 28 consecutive days. The primary outcome is pain
      severity. Secondary outcomes are functional status, patient satisfaction, and
      adverse events as reported in the trial. DISCUSSION: Qishe Pill is composed of
      processed Radix Astragali, Muscone, Szechuan Lovage Rhizome, Radix Stephaniae
      Tetrandrae, Ovientvine, and Calculus Bovis Artifactus. According to modern
      research and preparation standards, Qishe Pill is developed to improve on the
      various symptoms of cervical radiculopathy, especially for neck pain. As it has a
      potential benefit in treating patients with neck pain, we designed a double
      blind, prospective, randomized-controlled trial and would like to publish the
      results and conclusions later. If Qishe Pill can alleviate neck pain without
      adverse effects, it may be a unique strategy for the treatment of cervical
      radiculopathy. TRIAL REGISTRATION: This study is registered at
      ClinicalTrials.gov, NCT01274936.

PMID- 24099351
TI  - Test-retest reliability of behavioral measures of impulsive choice, impulsive
      action, and inattention.
AB  - Behavioral measures of impulsivity are widely used in substance abuse research,
      yet relatively little attention has been devoted to establishing their
      psychometric properties, especially their reliability over repeated
      administration. The current study examined the test-retest reliability of a
      battery of standardized behavioral impulsivity tasks, including measures of
      impulsive choice (i.e., delay discounting, probability discounting, and the
      Balloon Analogue Risk Task), impulsive action (i.e., the stop signal task, the
      go/no-go task, and commission errors on the continuous performance task), and
      inattention (i.e., attention lapses on a simple reaction time task and omission
      errors on the continuous performance task). Healthy adults (n = 128) performed
      the battery on two separate occasions. Reliability estimates for the individual
      tasks ranged from moderate to high, with Pearson correlations within the specific
      impulsivity domains as follows: impulsive choice (r range: .76-.89, ps < .001);
      impulsive action (r range: .65-.73, ps < .001); and inattention (r range: .38
      .42, ps < .001). Additionally, the influence of day-to-day fluctuations in mood,
      as measured by the Profile of Mood States, was assessed in relation to
      variability in performance on each of the behavioral tasks. Change in performance
      on the delay discounting task was significantly associated with change in
      positive mood and arousal. No other behavioral measures were significantly
      associated with mood. In sum, the current analysis demonstrates that behavioral
      measures of impulsivity are reliable measures and thus can be confidently used to
      assess various facets of impulsivity as intermediate phenotypes for drug abuse.

PMID- 24099352
TI  - The effects of nicotine on intrusive memories in nonsmokers.
AB  - Correlational research suggests that smoking increases risk of posttraumatic
      stress disorder (PTSD), though such research by nature cannot rule out third
      variable explanations for this relationship. The present study used an analogue
      trauma film design to experimentally test the effects of nicotine on the
      occurrence of intrusive memories. Fifty-four healthy nonsmokers were randomly
      assigned to ingest either a nicotine or placebo lozenge before viewing a film
      depicting motor vehicle accidents. Participants recorded intrusive memories
      immediately after the film and for a week via diary. Participants in the nicotine
      condition reported significantly more intrusive memories immediately after
      watching the film, yet no group differences emerged on intrusions or intrusion
      related distress reported during the following week. Among participants low in
      dispositional rumination, those who had ingested a nicotine lozenge reported more
      intrusions in the subsequent week than those in the placebo condition. These
      findings provide novel experimental evidence for the role of nicotine in
      increasing risk of PTSD and suggest that nicotine may contribute to trauma
      related rumination but not heightened reactivity to trauma cues.

PMID- 24099353
TI  - Does cue context matter? Examining the specificity of cue-related activation of
      positive and negative alcohol expectancies.
AB  - Consistent with the Encoding Specificity principle, positive alcohol expectancies
      may be activated by cues in drinking contexts because they are more closely
      associated with these cues in memory than are negative expectancies. However,
      there is little research examining the specificity of cue-induced alcohol
      expectancy activation. This study investigated the relative activation of
      positive and negative expectancies in response to positive and negative cue
      contexts. We also examined whether these effects were stronger for heavier and
      more problematic drinkers. College student drinkers were randomly assigned to
      listen to vignettes describing either positive or negative drinking scenarios
      (cue exposure). Participants also completed an implicit measure of alcohol
      expectancy activation (modified Stroop task) both before and after the cue
      exposure, as well as self-report measures of alcohol use and alcohol-related
      problems. We found that alcohol-related problems moderated the effects of cue
      condition on expectancy activation, such that specific activation of positive
      relative to negative expectancies in response to positive cues was observed only
      for drinkers with higher levels of alcohol problems. No differences in activation
      of positive versus negative expectancies were observed for more problematic
      drinkers in the negative cue condition or for less problematic drinkers in either
      cue condition. The results are partially consistent with the Encoding Specificity
      principle, showing that positive contextual cues can selectively activate
      positive alcohol expectancies for more problematic drinkers. Findings may have
      implications for interventions that target automatic expectancy processes,
      suggesting potential utility in targeting specific expectancies in specific
      contexts.

PMID- 24099355
TI  - Impulsivity and motor activity in aged, male Ts65Dn mice.
AB  - Attention deficit/hyperactivity disorder (ADHD) is more prevalent in children
      with Down syndrome than in typically developing children. The defining
      characteristics of ADHD include inattention, impulsivity, and hyperactivity. The
      main purpose of this study was to determine whether a mouse model of Down
      syndrome exhibited higher levels of impulsivity than controls. A secondary aim
      was to examine the effects of d-amphetamine (0.1-10 mg/kg) and fenfluramine (0.3
      10 mg/kg) on impulsivity. Seven male Ts65Dn and 9 male littermate control (LC)
      mice were trained under a response inhibition schedule of reinforcement; the main
      measure of impulsivity under this schedule is the mean wait time. After behavior
      stabilized, the mean wait time for the Ts65Dn mice was indistinguishable from
      that of the LC mice. Administration of 1 mg/kg d-amphetamine increased the mean
      wait time in both Ts65Dn and LC, though it was statistically significant only for
      the LC. However, no dose of fenfluramine altered the mean wait time in Ts65Dn or
      LC mice. An additional aim of these studies was to determine whether Ts65Dn mice
      displayed higher levels of motor activity than LC mice. A comparison of running
      wheel activity revealed no difference between Ts65Dn and LC mice. Thus, the
      results of the current studies suggest that aged, male Ts65Dn mice are no
      different from age-matched LC mice in terms of impulsivity or motor activity.

PMID- 24099356
TI  - An influence of delayed reinforcement on the effectiveness of psychostimulants to
      enhance indices of attention under a five-choice serial reaction time procedure
      in male rats.
AB  - The five-choice serial reaction time (5-CSRT) procedure has been considered a
      translational tool for assessments of the psychopharmacology of attention in
      preclinical research. Because greater sensitivity to delayed reinforcement may
      promote the development of attention-deficit/hyperactivity disorder (ADHD)
      symptoms, effects of reinforcer delay and psychostimulants on performances under
      a 5-CSRT procedure were determined. Male rats were trained to respond under a 5
      CSRT procedure with different delay-of-reinforcement conditions (0, 2, 4, 8, 16
      s), and effects of d-amphetamine, methylphenidate, and morphine (as a negative
      control) were assessed at 0- and 16-s delays. Under nondrug conditions, as the
      delay increased both response latency and the number of trials in which a
      response did not occur (omissions) increased, and the percent correct on trials
      when responses were emitted decreased. Only modest increases in the percent
      correct were found with psychostimulants during the 0-s delay condition; however,
      more substantial enhancements were found with a 16-s delay. Consistent effects of
      both psychostimulants at either delay on omissions and response latency were not
      observed. Morphine increased omissions and response latency at both delays and
      decreased the percent correct (16-s delay). Generally, responses during the
      intertrial interval were not systematically affected under any condition. The
      current results demonstrate that measures of attention in a 5-CSRT procedure are
      sensitive to changes in the delay to reinforcer delivery. More important,
      psychostimulants significantly enhanced a measure of attention only when
      reinforcers were delayed, which may be reflective of the psychopharmacological
      mechanisms involved with clinical treatment of ADHD symptoms.

PMID- 24099357
TI  - Methylphenidate and atomoxetine enhance sensory-evoked neuronal activity in the
      visual thalamus of male rats.
AB  - Attention deficits and inappropriate regulation of sensory signal processing are
      hallmarks of many neuropsychiatric conditions, including attention deficit
      hyperactivity, for which methylphenidate (MPH) and atomoxetine (ATX) are commonly
      prescribed therapeutic treatments. Despite their widespread use and known
      mechanism of blocking reuptake of catecholamine transmitters in the brain, the
      resultant actions on individual neuron and neural circuit function that lead to
      therapeutic efficacy are poorly understood. Given the ability of MPH and ATX to
      improve cognitive performance in humans and rodent assays of attention, we were
      interested in their influence on early sensory processing in the dorsal lateral
      geniculate nucleus (dLGN), the primary thalamic relay for visual information from
      the retina to the visual cortex. In male rats, dLGN neuronal responses to light
      stimuli were altered in multiple ways after doses of MPH or ATX observed to
      enhance performance in visually guided assays of attention (MPH = 2 mg/kg; ATX =
      0.5 mg/kg). Latencies to response onset and to the peak of the primary response
      were decreased, while the peak intensity and area of the primary response were
      increased. In addition, some cells that were unresponsive to light stimuli prior
      to drug treatment displayed a "gating effect," wherein prominent responses to
      light stimuli were evident after drug administration. Our results begin to reveal
      unique effects of MPH and ATX in enhancing sensory signal transmission through
      visual circuitry, and may yield new insights for understanding the
      pathophysiology of certain cognitive disorders and inform development of improved
      therapeutic treatments for these conditions.

PMID- 24099359
TI  - Misuse of prescription stimulants among college students: a review of the
      literature and implications for morphological and cognitive effects on brain
      functioning.
AB  - Prescription stimulant medication, the most frequently recommended treatment for
      college students with attention deficit/hyperactivity disorder (ADHD), has become
      increasingly available on college campuses. Research investigating prescription
      stimulant misuse among college students indicates that significant numbers of
      students without ADHD are taking prescription stimulants to enhance their
      cognitive performance. This article systematically reviews studies concerning
      misuse of prescription stimulants among college students with and without ADHD as
      well as the cognitive and morphological brain changes associated with
      prescription stimulants in humans and other animals. Whether these morphological
      changes are accompanied by improved cognitive performance remains equivocal.
      Implications of this body of literature are discussed and suggestions for future
      research are advanced.

PMID- 24099358
TI  - Methylphenidate does not influence smoking-reinforced responding or attentional
      performance in adult smokers with and without attention deficit hyperactivity
      disorder (ADHD).
AB  - Individuals with Attention Deficit Hyperactivity Disorder (ADHD) smoke cigarettes
      at rates higher than the general population and questions have been raised about
      how stimulant drugs-the frontline pharmacological treatment for ADHD-influence
      smoking risk and behavior in those with ADHD. In the present study adult regular
      smokers with (n = 16) and without (n = 17) ADHD participated in 3 experimental
      sessions in which they completed a Progressive Ratio (PR) task to measure the
      relative reinforcing effects of cigarette smoking and money after oral
      administration of placebo and 2 active doses of methylphenidate (10 mg and 40
      mg). We also measured attention and inhibitory control via a Continuous
      Performance Test (CPT). Methylphenidate had no effect on smoking-reinforced
      responding, attention, or inhibitory control in either group. Attention and
      inhibitory control were associated with smoking-reinforced responding, but
      unsystematically and only in the non-ADHD group. Several design features, such as
      the value of the monetary response option, the PR schedule, and the potential
      effects of smoking on attention and inhibitory control, could have contributed to
      the negative findings and are discussed as such. Although inconsistent with some
      previous human laboratory studies of stimulant drugs and smoking, results are
      consistent with recent trials of stimulant drugs as adjuncts for smoking
      cessation in adult smokers with ADHD. In general, methylphenidate at mild and
      moderate doses did not influence the relative reinforcing effects of cigarette
      smoking in adults with and without ADHD.

PMID- 24099360
TI  - Music increases alcohol consumption rate in young females.
AB  - Previous field research has shown that individuals consumed more alcohol and at a
      faster rate in environments paired with loud music. Theoretically, this effect
      has been linked to approach/avoidance accounts of how music influences arousal
      and mood, but no work has tested this experimentally. In the present study,
      female participants (n = 45) consumed an alcoholic (4% alcohol-by-volume)
      beverage in one of three contexts: slow tempo music, fast tempo music, or a no
      music control. Results revealed that, compared with the control, the beverage was
      consumed fastest in the two music conditions. Interestingly, whereas arousal and
      negative mood declined in the control condition, this was not the case for either
      of the music conditions, suggesting a downregulation of alcohol effects. We
      additionally found evidence for music to disrupt sensory systems in that,
      counterintuitively, faster consumption was driven by increases in perceived
      alcohol strength, which, in turn, predicted lower breath alcohol level (BrAL).
      These findings suggest a unique interaction of music environment and psychoactive
      effects of alcohol itself on consumption rate. Because alcohol consumed at a
      faster rate induces greater intoxication, these findings have implications for
      applied and theoretical work.

PMID- 24099362
TI  - Advanced oxygen reduction electrocatalyst based on nitrogen-doped graphene
      derived from edible sugar and urea.
AB  - Designing and fabricating advanced oxygen reduction reaction (ORR)
      electrocatalysts is critical importance for the sake of promoting widespread
      application of fuel cells. In this work, we report that nitrogen-doped graphene
      (NG), synthesized via one-step pyrolysis of naturally available sugar in the
      presence of urea, can serve as metal-free ORR catalyst with excellent
      electrocatalytic activity, outstanding methanol crossover resistance as well as
      long-term operation stability in alkaline medium. The resultant NG1000 (annealed
      at 1000  degrees C) exhibits a high kinetic current density of 21.33 mA/cm(2) at 
      0.25 V (vs Ag/AgCl) in O2-saturated 0.1 M KOH electrolyte, compared with 16.01
      mA/cm(2) at -0.25 V for commercial 20 wt % Pt/C catalyst. Notably, the NG1000
      possesses comparable ORR half-wave potential to Pt/C. The effects of pyrolysis
      temperature on the physical prosperity and ORR performance of NG are also
      investigated. The obtained results demonstrate that high activation temperature
      (1000  degrees C) results in low nitrogen doping level, high graphitization
      degree, enhanced electrical conductivity, and high surface area and pore volume,
      which make a synergetic contribution to enhancing the ORR performance for NG. 

PMID- 24099361
TI  - Effects of a novel CB1 agonist on visual attention in male rats: role of strategy
      and expectancy in task accuracy.
AB  - The effects of cannabinoid CB1 agonists (including Delta9-tetrahydrocannabinol,
      the main psychoactive component of marijuana) on attention are uncertain, with
      reports of impairments, no effects, and occasionally performance enhancements. To
      better understand these effects, we sought to uncover a role of changing online
      (within-session) strategy as a possible mediator of the effects of the novel,
      potent CB1 agonist AM 4054, on a model of sustained attention in male Sprague
      Dawley rats. In this operant, two-choice reaction time (RT) task, AM 4054
      decreased accuracy in an asymmetric manner; that is, performance was spared on
      one lever but impaired on the other. Furthermore, this pattern was enhanced by
      the outcome of the previous trial such that AM 4054 strengthened a win-stay
      strategy on the "preferred" lever and a lose-shift strategy on the "nonpreferred"
      lever. This pattern is often found in tests of expectancy; therefore, in a second
      experiment AM 4054 enhanced expectancy that we engendered by altering the
      probability of the two stimulus cues. Accuracy was impaired in reporting the less
      frequent cue, but only after two or more presentations of the more frequent cue.
      Taking the results of the experiments together, AM 4054 engendered expectancy by
      increasing the role of previous trial location and outcome on performance of
      future trials, diminishing stimulus control (and therefore, accuracy). This novel
      effect of CB1 receptor agonism may contribute to the deleterious effects of
      cannabinoids on attention.

PMID- 24099363
TI  - Source water changes and energy extraction activities in the Monongahela River,
      2009-2012.
AB  - Fossil fuel wastewaters disposed of to surface waters used as sources for potable
      water supply have the potential to affect finished drinking water quality since
      these produced waters contain high concentrations of constituents that are of
      concern to drinking water providers (including dissolved solids, sulfate,
      chloride, and bromide). A 3-year field study in the Monongahela River was
      conducted to determine how constituent concentrations and associated loads
      changed in the river basin, and whether these changes were caused by surface
      discharges associated with shale gas extraction. Low flow during the dry summer
      of 2010 contributed to increases in bromide concentrations at drinking water
      intakes; however, similar low flow conditions in summer of 2012 did not,
      indicating bromide loads discharged to the river decreased from 2010 to 2012.
      Analysis of bromide to chloride ratios as an indicator of fossil fuel associated
      wastewaters showed significant increases in Br/Cl at drinking water intakes over
      the first year of the study (2009-2010). This indicator ratio declined in the
      final year of the study (2011-2012), likely associated with a voluntary decrease
      in the use of surface-discharging treatment plants for shale gas wastewater
      disposal. Predictions of future concentrations based on historical flow data are
      also presented. 

PMID- 24099364
TI  - Hydroxyclerodanes from Salvia shannoni.
AB  - Six new hydroxyclerodanes (1-6), named sepulturins A-F, and four known diterpenes
      were isolated from the leaves of Salvia shannoni. The structures of these
      compounds were established by extensive analysis of their NMR and MS
      spectroscopic data. The relative configurations of compounds 1 and 2 were
      determined by NOESY experiments and were confirmed by single-crystal X-ray
      diffraction studies. All of the isolated diterpenes possess tertiary OH groups.
      The structure of infuscatin (7), a clerodane previously isolated from S.
      infuscata, was revised. Cytotoxic, antiprotozoal, and anti-inflammatory
      activities of these compounds were evaluated. 

PMID- 24099365
TI  - Balancing quantity and quality in emergency medicine training for interns.

PMID- 24099366
TI  - The need to maintain quality and build capacity for emergency medicine training.

PMID- 24099367
TI  - Review article: Improving the hospital clinical handover between paramedics and
      emergency department staff in the deteriorating patient.
AB  - Clinical communication and recognising and responding to a deteriorating patient
      are key current patient safety issues in healthcare. The aim of this literature
      review is to identify themes associated with aspects of the hospital clinical
      handover between paramedics and ED staff that can be improved, with a specific
      focus on the transfer of care of a deteriorating patient. Extensive searches of
      scholarly literature were conducted using the main medical and nursing electronic
      databases, including Cumulative Index to Nursing and Allied Health Literature,
      Medline and PubMed, during 2011 and again in July 2012. Seventeen peer-reviewed
      English-language original quantitative and qualitative studies from 2001 to 2012
      were selected and critically appraised using an evaluation tool based on
      published instruments. Relevant themes identified were: professional
      relationships, respect and barriers to communication; multiple or repeated
      handovers; identification of staff in the ED; significance of vital signs; need
      for a structured handover tool; documentation and other communication methods and
      education and training to improve handovers. The issues raised in the literature
      included the need to: produce more complete and concise handovers, create
      respectful and effective communication, and identify staff in the ED. A
      structured handover tool such as ISBAR (a mnemonic covering Introduction,
      Situation, Background, Assessment and Recommendations) would appear to provide a
      solution to many of these issues. The recording of vital signs and transfer of
      these data might be improved with better observation systems incorporating early
      warning strategies. More effective teamwork could be achieved with further
      clinical communications training. 

PMID- 24099369
TI  - A cohort study of chest pain patients discharged from the emergency department
      for early outpatient treadmill exercise stress testing.
AB  - OBJECTIVE: Guidelines on intermediate-risk chest pain, based on consensus alone,
      recommend inpatient provocative testing after infarct exclusion. Inpatient
      testing exceeds capacity in many hospitals, so guidelines concede outpatient
      testing within 72 h is acceptable. We performed a cohort study of chest pain
      patients having early outpatient treadmill exercise stress testing (EST).
      METHODS: All chest pain patients discharged from our emergency with booked
      outpatient treadmill EST during the 2008 to 2010 calendar years were included.
      There were no exclusions. The primary outcome was diagnosis of major coronary
      artery disease among stress test attendees. Secondary outcomes were time to
      stress test booking, representations with chest pain or death within 30 days.
      RESULTS: The cohort consisted of 657 patients: 59% men, mean age 53.2 years. Time
      from discharge to stress test averaged 10.6 days and 73% of patients attended. Of
      patients who attended, 14% had a positive test and 13% an inconclusive result.
      These patients were older than those with negative results (P < 0.001). Four
      patients (0.8% of attendees) were diagnosed with major coronary artery disease.
      There were no representations with acute myocardial infarction and no deaths
      identified. CONCLUSIONS: Outpatient treadmill EST an average of 10 days post
      discharge from emergency with chest pain did not result in adverse events despite
      reasonably high positive stress test rates. Consensus-based recommendations for
      inpatient testing or outpatient testing within 72 h of discharge should be
      reviewed in light of these data.

PMID- 24099370
TI  - Accuracy of computed tomography of the kidneys, ureters and bladder
      interpretation by emergency physicians.
AB  - OBJECTIVE: The study aims to determine the interpretation accuracy of computed
      tomography of the kidneys, ureters and bladder (CT-KUB) by emergency physicians
      (EPs) compared with the formal radiology report, as the reference standard, in
      patients with suspected acute urinary tract calculous disease. METHODS: A sample
      of 20 consecutive CT-KUB scans for suspected acute calculous disease was compiled
      from the medical imaging department of an adult tertiary teaching hospital. Ten
      EPs with a minimum of 2 years' experience post-Fellowship interpreted each scan
      using a template form. The total sample of 200 reports by EPs was compared with
      the formal radiology report for agreement in detecting renal tract stones, signs
      of obstruction and other clinical findings. Interrater agreement and the kappa
      statistic were used for comparative data analysis. RESULTS: There was a high
      level of agreement (%, kappa value) between EPs and radiologists for the
      detection of large (>=5 mm) calculi (94.5%, kappa 0.89), signs of obstruction
      (93%, kappa 0.86) and clinically significant findings (90%, kappa 0.78). The
      level of agreement was low for the detection of small (<5 mm) calculi (79%, kappa
      0.48) and clinically non-significant findings (67.5%, kappa 0.33). CONCLUSION:
      EPs can accurately detect clinically significant acute calculous disease and
      signs of obstruction on CT-KUB, allowing for ongoing acute management and early
      disposition of the patient. However, their findings should be verified against
      the formal radiology report when available.

PMID- 24099371
TI  - Effect of interprofessional student-led beds on emergency department performance
      indicators.
AB  - OBJECTIVE: The study aims to compare ED performance indicators between patients
      managed by students in an inter-professional learning (IPL) programme and
      comparable patients receiving usual ED care. METHODS: An IPL programme ran for
      five separate 2 week periods during 2012. Four student-led beds were managed by
      four final year students (two medical, two nursing). Four control beds were
      matched for patient acuity. Data were gathered electronically from the ED
      information system. Comparisons of baseline characteristics and a range of ED
      performance indicators were made between patients managed in the student-led and
      control beds. Patient satisfaction with student care was surveyed. RESULTS:
      Characteristics of the 369 study and 365 control patients were similar. Median
      times to being seen by a nurse and a doctor were not significantly different
      between student-led and control beds, at 50 (19-103) versus 45 (20-93) min, and
      84 (28-162) versus 91 (41-165) min, respectively. Median time to inpatient
      referral for admitted patients was significantly longer in student-led compared
      with control beds, being 142 (65-249) versus 101.5 (48-200) min, respectively.
      Median lengths of stay were similar between the student-led and control groups,
      being 263 (201-343) versus 303.5 (204-384) min for discharged patients, and 866
      (571-1238) versus 745.5 (487-1168) min for inpatient ward admissions. Patients
      reported high levels of satisfaction with student care. CONCLUSION: There was
      little difference in performance indicators between patients managed by student
      teams as part of an IPL programme and a similar group receiving usual ED care.

PMID- 24099368
TI  - Australasian Resuscitation In Sepsis Evaluation trial statistical analysis plan.
AB  - BACKGROUND: The Australasian Resuscitation In Sepsis Evaluation (ARISE) study is
      an international, multicentre, randomised, controlled trial designed to evaluate
      the effectiveness of early goal-directed therapy compared with standard care for
      patients presenting to the ED with severe sepsis. OBJECTIVE: In keeping with
      current practice, and taking into considerations aspects of trial design and
      reporting specific to non-pharmacologic interventions, this document outlines the
      principles and methods for analysing and reporting the trial results. The
      document is prepared prior to completion of recruitment into the ARISE study,
      without knowledge of the results of the interim analysis conducted by the data
      safety and monitoring committee and prior to completion of the two related
      international studies. METHODS: The statistical analysis plan was designed by the
      ARISE chief investigators, and reviewed and approved by the ARISE steering
      committee. The data collected by the research team as specified in the study
      protocol, and detailed in the study case report form were reviewed. Information
      related to baseline characteristics, characteristics of delivery of the trial
      interventions, details of resuscitation and other related therapies, and other
      relevant data are described with appropriate comparisons between groups. The
      primary, secondary and tertiary outcomes for the study are defined, with
      description of the planned statistical analyses. RESULTS: A statistical analysis
      plan was developed, along with a trial profile, mock-up tables and figures. A
      plan for presenting baseline characteristics, microbiological and antibiotic
      therapy, details of the interventions, processes of care and concomitant
      therapies, along with adverse events are described. The primary, secondary and
      tertiary outcomes are described along with identification of subgroups to be
      analysed. CONCLUSION: A statistical analysis plan for the ARISE study has been
      developed, and is available in the public domain, prior to the completion of
      recruitment into the study. This will minimise analytic bias and conforms to
      current best practice in conducting clinical trials.

PMID- 24099372
TI  - Taking blood cultures from a newly established intravenous catheter in the
      emergency department does not increase the rate of contaminated blood cultures.
AB  - OBJECTIVE: It has been suggested that blood cultures drawn from vascular
      catheters have a higher false positive rate than those drawn by venepuncture. In
      the face of institutionally imposed practice change prohibiting obtaining blood
      cultures from intravenous (i.v.) catheters in the ED, our aim of was to compare
      the rate of contaminated blood cultures between those taken from recently placed
      i.v. catheters and those taken by direct venepuncture. METHOD: Prospective, non
      randomised, observational study comparing the rate of contaminated blood cultures
      for specimens taken from recently placed (<1 h) i.v. catheters and direct
      venepuncture in adult ED patients. Outcome of interest was the rate of false
      positive cultures. Analysis was by comparison of proportions (chi(2) -test).
      RESULTS: Four hundred seventy-two blood culture sets were studied. There were 65
      positive cultures, of which 49 (75%; 95% confidence interval [CI], 63-85%) were
      classified as true positive. The overall rate of contaminated blood cultures was
      3.4% (95% CI, 2.0-5.6%). There was no difference in false positive rate between
      blood cultures taken via venepuncture and those taken from a recently placed i.v.
      cannula (P = 0.52; odds ratio, 0.9; 95% CI, 0.33-2.44). CONCLUSION: We found no
      difference in contaminated blood culture rate between recently placed i.v.
      catheters and direct venepuncture when infection control procedures were
      followed.

PMID- 24099373
TI  - Current status of emergency airway management for elderly patients in Korea:
      Multicentre study using the Korean Emergency Airway Management Registry.
AB  - OBJECTIVE: We report the current status of emergency airway management in elderly
      Korean patients by analysing a multicentre registry database in order to provide
      quality emergency airway management to elderly patients. METHODS: The present
      study was designed as a retrospective, subgroup analysis of the registry of
      Korean Emergency Airway Management Society. We analysed rapid sequence intubation
      rate, first pass success rate and complications. RESULTS: The study consisted of
      4891 patients aged 65 years and older. The anticipation rate of difficult airway
      for age younger than 65 years, age 65 years and older and age 80 years and older
      was 15.8% (805/5090; 95% confidence interval [CI], 14.8-16.8), 12.0% (376/3146;
      95% CI, 10.9-13.1) and 8.5% (97/1140; 95% CI, 7.0-10.0) respectively (P < 0.001).
      Rapid sequence intubation was performed on 27.8% (1683/6051; 95% CI, 26.7-29.0)
      of the patients aged younger than 65 years, 26.5% (954/3599; 95% CI, 25.1-28.0)
      of the patients aged between 65 and 79 years and 25.2% (325/1292; 95% CI, 22.8
      27.6) of the patients aged 80 years and older (P = 0.097). First pass success was
      shown in 4837 (79.9%; 95% CI, 78.9-80.9) of 6051 patients aged less than 65
      years, 2868 (79.7%; 95% CI, 78.3-81.0) of 3599 patients aged between 65 and 79
      years and 1069 (82.7%; 95% CI, 80.5-84.7) of 1292 patients aged 80 years and
      older (P = 0.047). No differences were found between each group in the comparison
      of complication incidence by age (P = 0.686). CONCLUSIONS: Similar success and
      complication rates were found for emergency airway management in elderly patients
      compared with patients aged less than 65 years.

PMID- 24099374
TI  - Improvement in emergency department length of stay using an early senior medical
      assessment and streaming model of care: A cohort study.
AB  - OBJECTIVE: Australian EDs are required to conform to the National Emergency
      Access Target (NEAT): patients must be discharged within 4 h of arrival. The aim
      of the present study was to determine if a model of care called Senior Assessment
      and Streaming (SAS) would increase the proportion of patients achieving NEAT.
      METHODS: Stable, ambulant patients considered to have problems that early
      consultant-level assessment was likely to improve processing efficiency were
      streamed through a dedicated clinical area staffed by an ED physician, intern and
      nurse. The proportion of patients achieving NEAT were compared between days with
      or without SAS, adjusted for confounding variables. RESULTS: The 18 962 patients
      presented during the study, 6828 on days with SAS, 12 134 on days without. On
      days with SAS, there were more presentations, more admissions, lower access to
      ward beds and fewer staff working hours. After controlling for confounding, the
      odds of meeting NEAT on days with SAS was 15% higher compared with days without
      (odds ratio, 1.15; 95% confidence interval [CI], 1.07-1.24; P < 0.001). For the
      subgroups of patients admitted, discharged, triage category 3, 4, 5, or
      presentation 12.00-18.00 the odds of meeting NEAT on days with SAS was,
      respectively, 1.10 (95% CI, 0.98-1.23; P = 0.10), 1.17 (95% CI, 1.07-1.28; P <
      0.001), 1.17 (95% CI, 1.08-1.27; P < 0.001) and 1.19 (95% CI, 1.06-1.35; P =
      0.003). The odds of a patient not waiting to be seen on days with SAS was 28%
      lower compared with days without (odds ratio, 0.72; 95% CI, 0.58-0.90; P =
      0.003). CONCLUSION: Through the introduction of SAS, the present study has
      demonstrated that providing early senior medical assessment can improve an ED's
      ability to meet NEAT.

PMID- 24099375
TI  - Fireworks injuries in children: A prospective study during the festival of
      lights.
AB  - OBJECTIVE: We studied the epidemiology of paediatric firework-related injury in
      the urban population of Delhi during the festival of lights (Diwali). METHODS: In
      this prospective observational study, data were collected on the day of Diwali
      for two consecutive years, 2010 and 2011. All children with firework injuries
      coming to the emergency room were included in the study. Data were recorded in a
      predesigned proforma. RESULTS: Of the 65 cases, 75% were males and 25% were
      females; most children were more than 10 years of age and majority (90%) of them
      were unsupervised. Half (49%) of the cases were due to misuse of the fireworks or
      erratic behaviour, among which the most common observed mode was igniting cracker
      while holding it (18 cases; 24% of total injuries), which led to injuries to the
      hand and palm. Device failure was the next common cause for firework injuries,
      including unexpected blast of the crackers and string bomb as the most common.
      Overall, the most commonly injured body sites were hands (62%), face (32%) and
      eyes (10%). Crackers and string bomb mainly caused injuries to hands; fountains
      and gunpowder caused injuries to the face. Sixty (94%) children were managed
      conservatively and 5 (6%) required skin grafting and tendon repair. CONCLUSION:
      We recommend parental supervision especially for males, wearing non-synthetic and
      non-flowing clothes, promoting branded crackers and educational campaigns in
      schools to curtail the rising trend in firework-related injuries in the
      paediatric population.

PMID- 24099376
TI  - Level of agreement between prehospital and emergency department vital signs in
      trauma patients.
AB  - OBJECTIVES: Describe the level of agreement between prehospital (emergency
      medical service [EMS]) and ED vital signs in a group of trauma patients
      transported to an inner city Major Trauma Centre. We also sought to determine
      factors associated with differences in recorded vital sign measurements. METHODS:
      All adult patients meeting trauma triage criteria and transported directly from
      scene of injury by New South Wales Ambulance to our institution were included.
      The primary outcome was the difference in vital signs: heart rate (HR), systolic
      blood pressure (SBP), respiratory rate (RR) and Glasgow Coma Scale (GCS), between
      ED and EMS recorded measurements. Agreement was assessed using intraclass
      correlation coefficients and enhanced Bland-Altman plots. Multivariable linear
      regression models were used to determine factors associated with vital sign
      differences. RESULTS: The 1181 trauma patients met inclusion criteria. Intraclass
      correlation coefficients were as follows: GCS 0.74 (95% confidence interval [CI],
      0.37, 1.12); HR 0.41 (95% CI, 0.30, 0.53); SBP 0.37 (95% CI, 0.27, 0.46); and RR
      0.29 (95% CI, 0.06, 0.51). Bland-Altman derived 95% limits of agreement lay
      outside a priori limits of clinical agreement for SBP and RR and were within
      limits of clinical agreement for GCS and HR. SBP and HR differences were
      associated with prehospital airway and fluid intervention. CONCLUSIONS: Agreement
      was demonstrated between EMS and ED GCS scores but not RR and SBP recordings.
      Discrepancies appeared to reflect physiological changes in response to EMS
      initiated interventions. Trauma triage algorithms and risk models might need to
      take these measurement differences, and factors associated with them, into
      account.

PMID- 24099377
TI  - The Australasian College for Emergency Medicine curriculum revision: the road map
      to change.

PMID- 24099378
TI  - Between principle and compromise: We are all meat in someone else's sandwich.
AB  - Clinical leadership and workforce management are high profile topics in many
      recent healthcare journals and frequently the focus of discussion in this sectors
      dynamic environment. Emergency physicians, like their cousins in other medical
      specialties, are required to work collaboratively within an increasingly complex
      system in order to optimise the clinical outcomes of their patients. This article
      presents a reflective analysis using a fictional character, Ulysses, who
      encounters traps and potholes in his journey to clinical leadership and
      management enlightenment. 

PMID- 24099379
TI  - Acinetobacter bacteremia following Agkistrodon envenoming.

PMID- 24099380
TI  - Acute STEMI successfully treated with chest compression and defibrillation.

PMID- 24099381
TI  - Unusual case of cervicofacial surgical emphysema.

PMID- 24099382
TI  - Methaemoglobinaemia after ingestion of concrete casting antifreeze.

PMID- 24099383
TI  - Diagnosis of triceps tendon rupture with bedside ultrasonography.

PMID- 24099384
TI  - Luxatio erecta: Utilisation of the two-step reduction technique without
      intravenous sedation by an emergency nurse practitioner.

PMID- 24099385
TI  - Power of sharing the patient journey in implementation of evidence-based care in
      emergency departments.

PMID- 24099386
TI  - Re: Vaginal examination does not improve diagnostic accuracy in early pregnancy
      bleeding.

PMID- 24099387
TI  - Response to Re: Vaginal examination does not improve diagnostic accuracy in early
      pregnancy bleeding.

PMID- 24099388
TI  - Post-earthquake chronic illness.

PMID- 24099389
TI  - Development of a genetic linkage map for Sharon goatgrass (Aegilops sharonensis)
      and mapping of a leaf rust resistance gene.
AB  - Aegilops sharonensis (Sharon goatgrass), a diploid wheat relative, is known to be
      a rich source of disease resistance genes for wheat improvement. To facilitate
      the transfer of these genes into wheat, information on their chromosomal location
      is important. A genetic linkage map of Ae. sharonensis was constructed based on
      179 F2 plants derived from a cross between accessions resistant (1644) and
      susceptible (1193) to wheat leaf rust. The linkage map was based on 389 markers
      (377 Diversity Arrays Technology (DArT) and 12 simple sequence repeat (SSR) loci)
      and was comprised of 10 linkage groups, ranging from 2.3 to 124.6 cM. The total
      genetic length of the map was 818.0 cM, with an average interval distance between
      markers of 3.63 cM. Based on the chromosomal location of 115 markers previously
      mapped in wheat, the four linkage groups of A, B, C, and E were assigned to Ae.
      sharonensis (S(sh)) and homoeologous wheat chromosomes 6, 1, 3, and 2. The single
      dominant gene (designated LrAeSh1644) conferring resistance to leaf rust race
      THBJ in accession 1644 was positioned on linkage group A (chromosome 6S(sh)) and
      was flanked by DArT markers wpt-9881 (at 1.9 cM distal from the gene) and wpt
      6925 (4.5 cM proximal). This study clearly demonstrates the utility of DArT for
      genotyping uncharacterized species and tagging resistance genes where pertinent
      genomic information is lacking. 

PMID- 24099390
TI  - Application of resistance gene analog markers to analyses of genetic structure
      and diversity in rice.
AB  - Plant disease resistance gene analog (RGA) markers were designed according to the
      conserved sequence of known RGAs and used to map resistance genes. We used genome
      wide RGA markers for genetic analyses of structure and diversity in a global rice
      germplasm collection. Of the 472 RGA markers, 138 were polymorphic and these were
      applied to 178 entries selected from the USDA rice core collection. Results from
      the RGA markers were similar between two methods, UPGMA and STRUCTURE.
      Additionally, the results from RGA markers in our study were agreeable with those
      previously reported from SSR markers, including cluster of ancestral
      classification, genetic diversity estimates, genetic relatedness, and cluster of
      geographic origins. These results suggest that RGA markers are applicable for
      analyses of genetic structure and diversity in rice. However, unlike SSR markers,
      the RGA markers failed to differentiate temperate japonica, tropical japonica,
      and aromatic subgroups. The restricted way for developing RGA markers from the
      cDNA sequence might limit the polymorphism of RGA markers in the genome, thus
      limiting the discriminatory power in comparison with SSR markers. Genetic
      differentiation obtained using RGA markers may be useful for defining genetic
      diversity of a suite of random R genes in plants, as many studies show a
      differentiation of resistance to a wide array of pathogens. They could also help
      to characterize the genetic structure and geographic distribution in crops,
      including rice, wheat, barley, and banana. 

PMID- 24099391
TI  - Haplotype combination of polymorphisms in the ADIPOQ gene promoter is associated
      with growth traits in Qinchuan cattle.
AB  - Adiponectin modulates lipid and glucose metabolism in adipose tissues and is also
      related to bone metabolism. Polymorphisms in the ADIPOQ gene likely have an
      impact on growth traits in cattle. In this study, we examined the relationship
      between ADIPOQ polymorphisms and body measurement parameters in Chinese beef
      cattle. First, we sequenced ADIPOQ and 1.2 kb of DNA upstream of its promoter,
      and we found 14 polymorphisms. With the luciferase reporter assay, we showed that
      the two polymorphisms SNP PR_-135 A>G and PR_-68 G>C, which are located in the
      core region of promoter, influence promoter activity of ADIPOQ. Second, we
      identified three haplotypes involved in these two polymorphic sites: A (A-135/C
      68), B (A-135/G-68), and C (G-135/G-68). Haplotypes B and C are major haplotypes
      in five Chinese populations of cattle (Qinchuan, Nanyang, Jiaxian, Hazakh, and
      Chinese Holstein). We studied the effects of these three haplotypes on body
      measurements, gene expression, and promoter activity, and we found that the
      genotypes are associated with body measurement parameters in Qinchuan cattle.
      Individuals with genotype BC (AG/GG) had significantly higher body height and
      heart girth than others, and this result may be interpreted by the following two
      observations. The promoter activity with haplotype B (A/G) is significantly
      higher than those with A (A/C) and C (G/G) in driving reporter gene
      transcription; the ADIPOQ mRNA level in cattle with genotype BC (AG/GG) is
      relatively lower than that in cattle with genotype BB (AA/GG). 

PMID- 24099392
TI  - Comprehensive analysis of the homeodomain-leucine zipper IV transcription factor
      family in Cucumis sativus.
AB  - The class IV homeodomain-leucine zipper (HD-Zip IV) proteins are plant-specific
      transcriptional factors known to play crucial roles in plant growth and
      development. In this study, 11 cucumber (Cucumis sativus) HD-Zip IV genes were
      identified in the version 2 cucumber genome and found to be distributed unevenly
      across the chromosomes. The CsHDZIV (Cucumis sativus homeodomain-leucine zipper
      IV) gene family is smaller than in other studied species (except for rice)
      because of the absence of gene duplication events. Phylogenetic analysis showed
      that HD-Zip IV genes from cucumber, Arabidopsis, tomato, cotton, maize, and rice
      could be classified into five subgroups. All CsHDZIV genes appear to be derived
      from a basic module containing 11 exons in the coding region. Two conserved
      motifs of 21 and 19 nucleotides were found in the 3'-untranslated regions of six
      CsHDZIV genes, suggesting that post-transcriptional regulation may play a role in
      regulation of CsHDZIV genes. In addition, 6 of 11 CsHDZIV genes were found to
      undergo alternative splicing events. Reverse transcription PCR analysis showed
      that all CsHDZIV genes (except one) were expressed and showed preferential
      expression in reproductive organs. 

PMID- 24099393
TI  - Microsatellite analyses across three diverse vertebrate transcriptomes (Acipenser
      fulvescens, Ambystoma tigrinum, and Dipodomys spectabilis).
AB  - Historically, many population genetics studies have utilized microsatellite
      markers sampled at random from the genome and presumed to be selectively neutral.
      Recent studies, however, have shown that microsatellites can occur in transcribed
      regions, where they are more likely to be under selection. In this study, we
      mined microsatellites from transcriptomes generated by 454-pyrosequencing for
      three vertebrate species: lake sturgeon (Acipenser fulvescens), tiger salamander
      (Ambystoma tigrinum), and kangaroo rat (Dipodomys spectabilis). We evaluated (i)
      the occurrence of microsatellites across species; (ii) whether particular gene
      ontology terms were over-represented in genes that contained microsatellites;
      (iii) whether repeat motifs were located in untranslated regions or coding
      sequences of genes; and (iv) in silico polymorphism. Microsatellites were less
      common in tiger salamanders than in either lake sturgeon or kangaroo rats. Across
      libraries, trinucleotides were found more frequently than any other motif type,
      presumably because they do not cause frameshift mutations. By evaluating
      variation across reads assembled to a given contig, we were able to identify
      repeat motifs likely to be polymorphic. Our study represents one of the first
      comparative data sets on the distribution of vertebrate microsatellites within
      expressed genes. Our results reinforce the idea that microsatellites do not
      always occur in noncoding DNA, but commonly occur in expressed genes. 

PMID- 24099394
TI  - Classification of topological domains based on gene expression and regulation.
AB  - Tissue-specific gene expression is thought to be one of the major forces shaping
      mammalian gene order. A recent study that used whole-genome chromosome
      conformation assays has shown that the mammalian genome is divided into specific
      topological domains that are shared between different tissues and organisms.
      Here, we wanted to assess whether gene expression and regulation are involved in
      shaping these domains and can be used to classify them. We analyzed gene
      expression and regulation levels in these domains by using RNA-seq and enhancer
      associated ChIP-seq datasets for 17 different mouse tissues. We found 162 domains
      that are active (high gene expression and regulation) in all 17 tissues. These
      domains are significantly shorter, contain less repeats, and have more
      housekeeping genes. In contrast, we found 29 domains that are inactive (low gene
      expression and regulation) in all analyzed tissues and are significantly longer,
      have more repeats, and gene deserts. Tissue-specific active domains showed some
      correlation with tissue-type and gene ontology. Domain temporal gene regulation
      and expression differences also displayed some gene ontology terms fitting their
      temporal function. Combined, our results provide a catalog of shared and tissue
      specific topological domains and suggest that gene expression and regulation
      could have a role in shaping them. 

PMID- 24099395
TI  - The conservation of number and location of 18S sites indicates the relative
      stability of rDNA in species of Pentatomomorpha (Heteroptera).
AB  - Fluorescent in situ hybridization (FISH) with rDNA probes has been used for
      comparative cytogenetics studies in different groups of organisms. Although
      heteropterans are a large suborder within Hemiptera, studies using rDNA are
      limited to the infraorder Cimicomorpha, in which rDNA sites are present in the
      autosomes or sex chromosomes. We isolated and sequenced a conserved 18S rDNA
      region of Antiteuchus tripterus (Pentatomidae) and used it as a probe against
      chromosomes of 25 species belonging to five different families of
      Pentatomomorpha. The clone pAt05, with a length of 736 bp, exhibited a conserved
      stretch of 590 bp. FISH analysis with the probe pAt05 always demonstrated
      hybridization signals in sub-terminal positions, except for Euschistus heros.
      Apparently, there is a tendency for 18S rDNA sites to locate in autosomes, except
      for Leptoglossus gonagra and Euryophthalmus rufipennis, which showed signals in
      the m- and sex chromosomes, respectively. Although FISH has produced evidence
      that rearrangements are involved in rDNA repositioning, whether in different
      autosomes or between sex and m-chromosomes, we have no conclusive evidence of
      what were the pathways of these rearrangements based on the evolutionary history
      of the species studied here. Nevertheless, the diversity in the number of species
      analyzed here showed a tendency of 18S rDNA to remain among the autosomes. 

PMID- 24099396
TI  - A young traveller presenting with typhoid fever after oral vaccination: a case
      report.
AB  - INTRODUCTION: Typhoid fever is one of the most common vaccine-preventable
      diseases in travellers returning from tropical destinations. However, immunity
      and the immune response to infection are barely understood. CASE PRESENTATION: We
      report a case of tyhoid fever in a 29-year-old Caucasian, previously healthy
      woman who did not develop protective immunity or seroconversion of H or O
      antibodies neither after vaccination with the oral Ty21 vaccine, nor after
      infection with Salmonella typhi. CONCLUSIONS: This case highlights the
      insufficiencies of the current vaccination and the lack of a reliable, rapid
      serologic diagnostic tool for typhoid fever. With this case report, we aim to
      sensitize the reader that typhoid fever has to be taken into account as a
      differential diagnosis in patients even after vaccination and with negative
      serological test results.

PMID- 24099397
TI  - Nanoformulations for delivery of biomolecules: focus on liposomal variants for
      siRNA delivery.
AB  - The potency of biomolecules assures therapy for as well as prevention of many
      disorders. However, their stability and delivery to the site of action remain a
      major challenge for successful therapeutic application. With advantages of
      nanoformulations, such as systemic environmental protection, controlled and site
      specific release, many of these bio-molecules have found their place in
      preventive, curative, or immunization-based therapies. Nanoformulations have
      indeed become a boon for the delivery of biomolecules with such challenges. Among
      biomolecules, small interfering RNA (siRNA)-based therapeutics has broad range of
      applications for disorders that may be pathological, metabolic, or physiological.
      However, certain challenges with respect to biological and delivery constraints
      need a priori consideration. From this perspective, liposomal delivery has made
      substantial progress to meet most of the delivery-related (pharmacokinetic)
      problems associated with siRNA. Furthermore, need-based development has led to
      the evolution of variants of liposomes. In this review we focus on the scope of
      siRNA and the trend of rationalized development of liposomal variants to explore
      its potential therapeutic implication. 

PMID- 24099398
TI  - Dissolution criticality in developing solid oral formulations: from inception to
      perception.
AB  - Currently, dissolution testing has become a vital tool for accessing product
      performance, especially in the hierarchy of solid oral dosage forms. With
      advances in complicated, expensive, and sophisticated analytical instruments,
      characterization of formulations has become easier, but simple dissolution
      assembly is gradually gaining momentum from industrial environs as well as
      regulatory agencies. As such, simple dissolution testing involves many
      complexities which must be properly understood to reach correct conclusions. The
      appropriate selection of multiple parameters (e.g., apparatus, medium, agitation,
      etc.) involved in dissolution testing and understanding their impact on analysis
      require thorough subject knowledge. In the words of regulatory provisions, in
      vitro dissolution testing can become a surrogate for expensive and tedious
      bioequivalence studies in special cases (i.e., when a biowaiver is recommended).
      As a consequence, reduced human testing as well as lower product development cost
      ultimately benefit patients and society. Therefore, the dissolution science has
      recently become one of the keys for success for formulation scientists,
      especially generic manufacturers. While designing dissolution methodologies,
      generic manufacturers need to follow the respective regulatory guidelines at the
      product development stage; concomitant data are required for the approval
      process. This comprehensive review is an earnest attempt to acquaint readers with
      the history, contemporary practices, and relevant issues regarding dissolution
      which may become a guiding tool for overcoming challenges and opening better
      prospects in product development. 

PMID- 24099399
TI  - Nano-aggregates: emerging delivery tools for tumor therapy.
AB  - A plethora of formulation techniques have been reported in the literature for
      site-specific targeting of water-soluble and -insoluble anticancer drugs. Along
      with other vesicular and particulate carrier systems, nano-aggregates have
      recently emerged as a novel supramolecular colloidal carrier with promise for
      using poorly water-soluble drugs in molecular targeted therapies. Nano-aggregates
      possess some inherent properties such as size in the nanometers, high loading
      efficiency, and in vivo stability. Nano-aggregates can provide site-specific drug
      delivery via either a passive or active targeting mechanism. Nano-aggregates are
      formed from a polymer-drug conjugated amphiphilic block copolymer. They are
      suitable for encapsulation of poorly water-soluble drugs by covalent conjugation
      as well as physical encapsulation. Because of physical encapsulation, a maximum
      amount of drug can be loaded in nano-aggregates, which helps to achieve a
      sufficiently high drug concentration at the target site. Active transport can be
      achieved by conjugating a drug with vectors or ligands that bind specifically to
      receptors being overexpressed in the tumor cells. In this review, we explore
      synthesis and tumor targeting potential of nano-aggregates with active and
      passive mechanisms, and we discuss various characterization parameters, ex vivo
      studies, biodistribution studies, clinical trials, and patents. 

PMID- 24099400
TI  - Toward a theory of distinct types of "impulsive" behaviors: A meta-analysis of
      self-report and behavioral measures.
AB  - Impulsivity is considered a personality trait affecting behavior in many life
      domains, from recreational activities to important decision making. When extreme,
      it is associated with mental health problems, such as substance use disorders, as
      well as with interpersonal and social difficulties, including juvenile
      delinquency and criminality. Yet, trait impulsivity may not be a unitary
      construct. We review commonly used self-report measures of personality trait
      impulsivity and related constructs (e.g., sensation seeking), plus the opposite
      pole, control or constraint. A meta-analytic principal-components factor analysis
      demonstrated that these scales comprise 3 distinct factors, each of which aligns
      with a broad, higher order personality factor-Neuroticism/Negative Emotionality,
      Disinhibition versus Constraint/Conscientiousness, and Extraversion/Positive
      Emotionality/Sensation Seeking. Moreover, Disinhibition versus
      Constraint/Conscientiousness comprise 2 correlated but distinct subfactors:
      Disinhibition versus Constraint and Conscientiousness/Will versus
      Resourcelessness. We also review laboratory tasks that purport to measure a
      construct similar to trait impulsivity. A meta-analytic principal-components
      factor analysis demonstrated that these tasks constitute 4 factors (Inattention,
      Inhibition, Impulsive Decision-Making, and Shifting). Although relations between
      these 2 measurement models are consistently low to very low, relations between
      both trait scales and laboratory behavioral tasks and daily-life impulsive
      behaviors are moderate. That is, both independently predict problematic daily
      life impulsive behaviors, such as substance use, gambling, and delinquency; their
      joint use has incremental predictive power over the use of either type of measure
      alone and furthers our understanding of these important, problematic behaviors.
      Future use of confirmatory methods should help to ascertain with greater
      precision the number of and relations between impulsivity-related components.

PMID- 24099401
TI  - Ochratoxin A mimotope from second-generation peptide library and its application
      in immunoassay.
AB  - With the advantage of replacing mycotoxins and their conjugates, mimotopes have
      been applied to immunoassays, the most common of which were seleted from random
      phage displayed peptide libraries. However, these mimotopes were limited by the
      diversities of the peptide libraries. The aim of this study was to demonstrate
      that a variety of mimotopes can be obtained by constructing a second-generation
      peptide library. Using mycotoxin ochratoxin A as a model system, a dodecapeptide
      mimotope was isolated after panning the second-generation peptide library. The
      half inhibition concentration of the chemiluminescent enzyme-linked immunosorbent
      assay setup with this mimotope was 0.04 ng/mL, and the linear range was 0.006
      0.245 ng/mL. The mimotope was also used to develop a qualitative dipstick assay
      with a cutoff level of 1 ng/mL. The method not only presents a high sensitivity
      but also contributes to the development of mimotope-based assays for mycotoxins
      avoiding the need of synthesizing toxic mycotoxin conjugates. 

PMID- 24099402
TI  - The use of mini-CEX in UK foundation training six years following its
      introduction: lessons still to be learned and the benefit of formal teaching
      regarding its utility.
AB  - BACKGROUND: The mini-clinical evaluation exercise (mini-CEX) is a widely used
      tool with a strong theoretical basis. It was introduced to UK foundation training
      in 2005. AIMS: To assess current experiences, opinions and attitudes towards mini
      CEX amongst foundation doctors, and explore what factors underpin these. METHODS:
      Data were collected from foundation trainees via an on-line questionnaire.
      RESULTS: Ninety-eight per cent of respondents had used mini-CEX during FY1,
      however, only 32% had ever received formal teaching regarding its use. In terms
      of understanding of the purpose of mini-CEX, only 30% of trainees commented on
      there being a formative aspect or requirement for feedback. The majority of
      trainees did not feel that mini-CEX was a useful part of their training. The main
      themes were the poor attitude and understanding of assessors and difficulties
      finding sufficient time. However, those who had received formal teaching as
      students regarding the use of mini-CEX were significantly more likely as
      postgraduates to find it beneficial (p = 0.031). CONCLUSIONS: A more concerted
      effort to educate trainees and assessors regarding the correct use of mini-CEX
      will enhance its educational value. Increased education during undergraduate
      training regarding use of formative assessment may lead to more effective
      utilisation in the postgraduate setting.

PMID- 24099403
TI  - Dopamine-agonist responsive Parkinsonism in a patient with the SANDO syndrome
      caused by POLG mutation.
AB  - BACKGROUND: Disorders of oxidative phosphorylation affects 1/5000 individuals and
      present heterogeneous involvement of tissues highly dependent upon ATP
      production. CASE PRESENTATION: Here we present the case of a 48-year-old woman
      carrying a homozygous mutation (p.A899T) in mitochondrial polymerase gamma (POLG)
      and manifesting with a complex neurological phenotype including Dopamine-agonist
      responsive Parkinsonism. CONCLUSION: This case report is further evidence that
      mitochondrial dysfunction might play a role in Parkinson's Disease pathogenesis
      and helps in identification of apparent mutation-specific clinical
      characteristics. Mutations in POLG should be looked for in cases of Parkinsonism,
      especially when multisystem neurological involvement is found.

PMID- 24099404
TI  - Predicting effects of kinase inhibitor in therapy for myeloid malignancies - the
      challenges in capturing disease heterogeneity.
AB  - Protein kinase inhibitors have proved to be effective and well tolerated in
      special form of malignant diseases in which targeted kinases play a central role
      in the development and progression of the malignant clone. In addition, the
      development of acquired drug resistance, due to new mutations or clonal
      evolution, during treatment is common. Methods for measuring the activity and
      predicting the efficacy of such compounds are warranted for evaluating individual
      responses to treatment, particularly in a context of widespread preclinical and
      clinical studies of protein kinase inhibitors in patients with heterogeneous
      myeloid malignancies. 

PMID- 24099405
TI  - First "themed issue" of Transfusion on thirty years of progress in blood safety
      since recognition of transfusion-associated AIDS.

PMID- 24099406
TI  - Human immunodeficiency virus transfusion transmission despite nucleic acid
      testing.

PMID- 24099407
TI  - Electronic spectroscopy of the 1,3-cyclopentadiene cation (C5H6+).
AB  - The gas-phase electronic spectrum of the 1,3-cyclopentadiene radical cation
      (C5H6(+)) has been investigated using resonance-enhanced photodissociation of
      mass-selected C5H6(+)-Ar complexes in a tandem mass spectrometer. The D1((2)B1) <
      D0((2)A2) band system spans the 460-620 nm range, while the D2((2)B1) <-
      D0((2)A2) band system appears between 320 and 370 nm. The band origins for the
      two systems are estimated to occur at 16,560 +/- 25 and 27,808 +/- 25 cm(-1),
      respectively. The D1 <- D0 band system exhibits a distinctive series of broad
      peaks, which, with the aid of molecular vibrational frequencies and geometries
      calculated using time-dependent density functional theory, are assigned to
      progressions in totally symmetric ring deformation modes. The broadening arises
      from the Franck-Condon activity of low-frequency out-of-plane vibrational modes,
      unresolved rotational contours, and possibly homogeneous lifetime broadening
      caused by rapid internal conversion to the ground electronic state.

PMID- 24099408
TI  - Neuromuscular disease and extubation dysphagia.
AB  - Post-extubation dysphagia is a common and serious problem. The presence of
      neuromuscular disease at the time of intubation is likely to increase this. Until
      recently, the prevalence and the association with length of intubation had not
      been clarified. Results published in this journal suggest that 93% of extubated
      patients with neuromuscular disease had post-extubation dysphagia, which in 33%
      of cases was considered severe. The number of days ventilated was the single
      predictor of severe dysphagia and a consequent prolonged hospital stay. Further
      work to build on these results to unravel the complex interplay between disease,
      trauma, and other unknown factors will be required. 

PMID- 24099409
TI  - High-level expression of a novel thermostable and mannose-tolerant beta
      mannosidase from Thermotoga thermarum DSM 5069 in Escherichia coli.
AB  - BACKGROUND: Mannan is one of the primary polysaccharides in hemicellulose and is
      widely distributed in plants. beta-Mannosidase is an important constituent of the
      mannan-degrading enzyme system and it plays an important role in many industrial
      applications, such as food, feed and pulp/paper industries as well as the
      production of second generation bio-fuel. Therefore, the mannose-tolerant beta
      mannosidase with high catalytic efficiency for bioconversion of mannan has a
      great potential in the fields as above. RESULTS: A beta-mannosidase gene (Tth
      man5) of 1,827 bp was cloned from the extremely thermophilic bacterium Thermotoga
      thermarum DSM 5069 that encodes a protein containing 608 amino acid residues, and
      was over-expressed in Escherichia coli BL21 (DE3). The results of phylogenetic
      analysis, amino acid alignment and biochemical properties indicate that the Tth
      Man5 is a novel beta-mannosidase of glycoside hydrolase family 5. The optimal
      activity of the Tth Man5 beta-mannosidase was obtained at pH 5.5 and 85 degrees C
      and was stable over a pH range of 5.0 to 8.5 and exhibited 2 h half-life at 90
      degrees C. The kinetic parameters K(m) and V(max) values for p-nitrophenyl-beta-D
      mannopyranoside and 1,4-beta-D-mannan were 4.36+/-0.5 mM and 227.27+/-1.59 MUmol
      min-1 mg-1, 58.34+/-1.75 mg mL-1 and 285.71+/-10.86 MUmol min-1 mg-1,
      respectively. The k(cat)/K(m) values for p-nitrophenyl-beta-D-mannopyranoside and
      1,4-beta-D-mannan were 441.35+/-0.04 mM-1 s-1 and 41.47+/-1.58 s-1 mg-1 mL,
      respectively. It displayed high tolerance to mannose, with a K(i) value of
      approximately 900 mM. CONCLUSIONS: This work provides a novel and useful beta
      mannosidase with high mannose tolerance, thermostability and catalytic
      efficiency, and these characteristics constitute a powerful tool for improving
      the enzymatic conversion of mannan through synergetic action with other mannan
      degrading enzymes.

PMID- 24099410
TI  - The activity of circulating dipeptidyl peptidase-4 is associated with subclinical
      left ventricular dysfunction in patients with type 2 diabetes mellitus.
AB  - BACKGROUND: Patients with type 2 diabetes mellitus (T2DM) present subclinical
      left ventricular systolic and/or diastolic dysfunction (LVD). Dipeptidyl
      peptidase-4 (DPP4) inactivates peptides that possess cardioprotective actions.
      Our aim was to analyze whether the activity of circulating DPP4 is associated
      with echocardiographically defined LVD in asymptomatic patients with T2DM.
      METHODS: In this cross-sectional study, we examined 83 T2DM patients with no
      coronary or valve heart disease and 59 age and gender-matched non-diabetic
      subjects. Plasma DPP4 activity (DPP4a) was measured by enzymatic assay and serum
      amino-terminal pro-brain natriuretic peptide (NT-proBNP) was measured by enzyme
      linked immunosorbent assay. LV function was assessed by two-dimensional
      echocardiographic imaging, targeted M-mode recordings and Doppler ultrasound
      measurements. Differences in means were assessed by t-tests and one-way ANOVA.
      Associations were assessed by adjusted multiple linear regression and logistic
      regression analyses. RESULTS: DPP4a was increased in T2DM patients as compared
      with non-diabetic subjects (5855 +/- 1632 vs 5208 +/- 957 pmol/min/mL, p < 0.05).
      Clinical characteristics and echocardiographic parameters assessing LV morphology
      were similar across DPP4a tertiles in T2DM patients. However, prevalence of LVD
      progressively increased across incremental DPP4a tertiles (13%, 39% and 71%, all
      p < 0.001). Multivariate regression analysis confirmed the independent
      associations of DPP4a with LVD in T2DM patients (p < 0.05). Similarly, multiple
      logistic regression analysis showed that an increase of 100 pmol/min/min plasma
      DPP4a was independently associated with an increased frequency of LVD with an
      adjusted odds ratio of 1.10 (95% CI, 1.04 to 1.15, p = 0.001). CONCLUSIONS: An
      excessive activity of circulating DPP4 is independently associated with
      subclinical LVD in T2DM patients. Albeit descriptive, these findings suggest that
      DPP4 may be involved in the mechanisms of LVD in T2DM.

PMID- 24099411
TI  - Cotrimoxazole and neonatal kernicterus: a review.
AB  - Sulfamethoxazole (SMX) and trimethoprim (TMP) individually and a combination
      known as cotrimoxazole (SMX-TMP) are widely used for the treatment of protozoan
      and bacterial infections. SMX-TMP is also one of the widely used antibiotics
      administered orally in neonates, along with gentamicin injection, for treating
      pneumonia and sepsis by home-based healthcare providers in Asian countries.
      Although the use of this drug has successfully reduced neonate mortality, there
      is a concern for it causing neurotoxicity. Previous clinical studies with
      sulfisoxazole have demonstrated occurrence of kernicterus in neonates. This
      sulfonamide is thought to displace bilirubin from its albumin-binding sites in
      plasma leading to an elevation of plasma bilirubin, which crosses the blood-brain
      barrier, reaches central neurons to cause kernicterus. We performed an extensive
      review of clinical and animal studies with cotrimoxazole, which showed no
      reported incidences of kernicterus with SMX-TMP use in neonates. EndNote,
      BasicBiosis, Embase, PubMed and Toxline database searches were conducted using
      specific keywords yielding 74 full-length articles relevant to the review. This
      review has taken into account various factors, including the disease itself,
      direct effects of the drug and its metabolism through conjugation and acetylation
      through a thorough review of the literature to examine the potentials of SMX-TMP
      to cause kernicterus in neonates. SMX-TMP in oral doses administered to neonates
      for 7-10 days is unlikely to cause kernicterus. Also, this review recommends
      warranting the need of future studies using animal models and clinical studies in
      humans to address SMX-TMP toxicity.

PMID- 24099412
TI  - Nutritional status is superior to the ECOG performance status in predicting the
      dose-intensity of the GEMOX chemotherapy regimen in patients with advanced
      cancer.
AB  - The increasing number of unfit patients calls for better risk assessment prior to
      initiating anti-tumor treatment. This is a major concern in the prevention and
      reduction of treatment-related complications. The aim of our study was to
      evaluate the nutritional status for the risk assessment of patients qualifying to
      receive the gemcitabine and oxaliplatin (GEMOX) regimen. This single-center,
      retrospective study examined baseline clinical and biological characteristics in
      a cohort of 165 unselected, consecutive cancer patients receiving GEMOX.
      Malnutrition was defined as either body mass index (BMI) <18.5 kg/m(2), body
      weight loss >10% over 3 mo, or albuminemia <35 g/L. A total of 165 patients
      (median age 61 yr, PS 0-1: 71%) were studied. Malnutrition was seen in 43% of PS
      0-1 patients, vs. 60% of PS 2 and 66% of PS 3 patients (P > 0.05). Median
      relative dose-intensity was 0.90 (0.17-1.04). GEMOX dose-intensity correlated
      negatively with loss of baseline weight (r = -0.24, P < 0.02). In patients who
      did not complete more than 2 cycles of chemotherapy, median PS (P < 0.01), mean C
      reactive protein (CRP; P < 0.01), and mean albuminemia (P < 0.05) were,
      respectively, significantly higher, higher, and lower. Malnutrition is associated
      with a high risk of early discontinuance of treatment. Systematic basal
      evaluation of the nutritional status, including albuminemia and BMI, is
      recommended.

PMID- 24099413
TI  - Metastatic Merkel cell carcinoma (MCC) of pancreas and breast: a unique case.
AB  - Merkel cell carcinoma (MCC) is a rare potentially fatal skin tumor affecting
      older and immunosuppressed individuals. It is highly malignant with high rates of
      metastasis and poor survival.We present a case of a 67-year-old woman with a
      palpable mass in the upper abdomen. An abdominal CT revealed a mass in the tail
      of the pancreas. Two weeks before, lumpectomy of a 3.5 cm tumor of the left
      breast had been performed. Histology showed a primary neuroendocrine carcinoma of
      the mammary gland. The patient's medical history was significant for a 0.7 * 0.9
      cm MCC removed from her left forearm 2.5 years ago. There was no evidence of
      vascular involvement or peritoneal disease and by all criteria was resectable. A
      somatostatin receptor scintigraphy showed an enhanced uptake in the pancreatic
      tail region. The tumor was immunohistochemically strong staining for
      synaptophysin and CD56. The diagnosis of a metastatic-MCC in the tail of the
      pancreas was made. Further histological investigation of the prior removed
      neuroendocrine breast tumor and the MCC of the left forearm confirmed
      neuroendocrine origin and identical histology to the previously resected MCC of
      the left forearm. In this article, we aim to highlight that MCC has the potential
      to spread even in unusual organs, such as pancreas or breast, and therefore a
      diligent follow-up should be applied in patients with MCC. 

PMID- 24099415
TI  - Development of nonstick and drug-loaded wound dressing based on the hydrolytic
      hydrophobic poly(carboxybetaine) ester analogue.
AB  - A novel biocompatible polymer is developed for antimicrobial and nonstick
      coatings of wound dressing. The polymer is formed by copolymerization of
      carboxybetaine ester analogue methacrylate (CB-ester) and small partial
      poly(ethylene glycol) methacrylate (PEGMA) for cross-linking by hexamethylene
      diisocyanate (HDI), which is highly resistant to nonspecific protein adsorption
      and mammalian cell attachment after a quick hydrolysis. A small hydrophobic drug,
      aspirin, can be incorporated into the new polymer and slowly released to inhibit
      microorganism growth while the new polymer shows very low cytotoxicity. Moreover,
      the wound dressing, the new polymer coated medical gauze, shows good mechanic
      properties, such as flexibility and strength, for medical application. After all,
      this new nonfouling polymer offers great potential for an antimicrobial wound
      dressing and other applications. 

PMID- 24099414
TI  - Study on psychoeducation enhancing results of adherence in patients with
      schizophrenia (SPERA-S): study protocol for a randomized controlled trial.
AB  - BACKGROUND: Poor adherence to pharmacotherapy negatively affects the course and
      the outcome of schizophreniaspectrum psychoses, enhancing the risk of relapse.
      Falloon and coworkers developed a Psychoeducation Program aimed at improving
      communication and problem-solving abilities in patients and their families. This
      study set out to evaluate changes in adherence to pharmacotherapy in patients
      diagnosed with schizophrenia-spectrum psychoses, by comparing one group exposed
      to the Falloon Psychoeducation Program (FPP) with another group exposed to family
      supportive therapy with generic information on the disorders. METHODS: 340
      patients diagnosed with schizophrenia and related disorders according to
      standardized criteria from 10 participating units distributed throughout the
      Italian National Health System (NHS), will be enrolled with 1:1 allocation by the
      method of blocks of randomized permutations. Patients will be reassessed at 6, 12
      and 18 months after start of treatment (duration: 6 months).The primary objective
      is to evaluate changes in adherence to pharmacotherapy after psychoeducation.
      Adherence will be assessed at three-month intervals by measuring blood levels of
      the primary prescribed drug using high pressure liquid chromatography, and via
      the Medication Adherence Questionnaire and a modified version of the Adherence
      Interview. Secondary objectives are changes in the frequency of relapse and
      readmission, as the main indicator of the course of the disorder.Enrolled
      patients will be allocated to the FPP (yes/no) randomly, 1:1, in a procedure
      controlled by the coordinating unit; codes will be masked until the conclusion of
      the protocol (or the occurrence of a severe negative event). The raters will be
      blind to treatment allocation and will be tested for blinding after treatment
      completion. Intention-to-treat will be applied in considering the primary and
      secondary outcomes. Multiple imputations will be applied to integrate the missing
      data. The study started recruitment in February 2013; the total duration of the
      study is 27 months. DISCUSSION: If the psychoeducation program proves effective
      in improving adherence to pharmacotherapy and in reducing relapse and
      readmissions, its application could be proposed as a standard adjunctive
      psychosocial treatment within the Italian NHS. TRIAL REGISTRATION: Protocol
      Registration System of ClinicalTrials.gov NCT01433094; registered on 20 August
      2011; first patient was randomized on 12 February 2013.

PMID- 24099416
TI  - The presence of CD4 counts for the management of HIV patients in East Africa: a
      multicentred study.
AB  - New WHO guidance stipulates six-monthly CD4 testing and treatment initiation at
      CD4 less than 350. This study aimed to determine the presence of CD4 results in
      patient records across five care facilities in Kenya, and to identify factors
      associated with the presence of CD4 count. This is a cross-sectional study of
      consecutive outpatients. Participants completed self-reported outcomes of
      demographics, and both physical and mental health dimensions of quality of life
      and function; charts were reviewed for a CD4 count in the previous 13 months; 548
      patients participated. For those diagnosed during the 13-month study period, 7.1%
      of the sample had no CD4 result on record. For those diagnosed prior to the
      study, 8.7% had no result. Multivariate logistic regression revealed that 30 days
      post-HIV diagnosis, facility and antiretroviral therapy use were associated with
      the odds of having a CD4 result on file. At six months, poverty and prevalence of
      multidimensional problems were associated with lack of CD4 result. For those
      diagnosed prior to the observation period, education level was associated with
      more infrequent CD4 counts, and facility and number of dependants were associated
      with odds of a CD4 result within six months. Our data suggest inconsistencies in
      CD4 results availability within and between facilities. Implementation of new
      guidance will require a shift in practice. 

PMID- 24099417
TI  - Biological uptake and depuration of radio-labeled graphene by Daphnia magna.
AB  - Graphene layers are potential candidates in a large number of applications.
      However, little is known about their ecotoxicological risks largely as a result
      of a lack of quantification techniques in complex environmental matrices. In this
      study, graphene was synthesized by means of graphitization and exfoliation of
      sandwich-like FePO4/dodecylamine hybrid nanosheets, and (14)C was incorporated in
      the synthesis. (14)C-labeled graphene was spiked to artificial freshwater and the
      uptake and depuration of graphene by Daphnia magna were assessed. After exposure
      for 24 h to a 250 MUg/L solution of graphene, the graphene concentration in the
      organism was nearly 1% of the organism dry mass. These organisms excreted the
      graphene to clean artificial freshwater and achieved roughly constant body
      burdens after 24 h depuration periods regardless of the initial graphene exposure
      concentration. Addition of algae and humic acid to water during the depuration
      period resulted in release of a significant fraction (>90%) of the accumulated
      graphene, but some still remained in the organism. Accumulated graphene in adult
      Daphnia was likely transferred to the neonates. The uptake and elimination
      results provided here support the environmental risk assessment of graphene and
      the graphene quantification method is a powerful tool for additional studies. 

PMID- 24099418
TI  - Myelodysplastic syndrome with pulmonary tumor thrombotic microangiopathy in an 11
      year-old male patient.
AB  - Myelodysplastic syndrome (MDS) and pulmonary tumor thrombotic microangiopathy
      (PTTM) are independently rare in the pediatric population. This report describes
      an 11-year-old male patient who initially presented with respiratory distress and
      cardiovascular collapse. A large left main pulmonary artery embolus and multiple,
      smaller pulmonary thromboemboli were widely dispersed throughout both lungs.
      Despite aggressive supportive care, he died within seven hours of admission. A
      complete postmortem examination was performed, leading to the diagnoses of
      primary MDS and microthrombi in the lungs, including the characteristic
      fibroproliferative lesions seen in PTTM. Individually, both conditions are
      extremely uncommon, and therefore the coincidence of these 2 conditions in a
      child is singularly unique.

PMID- 24099420
TI  - Transgenic soybeans and soybean protein analysis: an overview.
AB  - To meet the increasing global demand for soybeans for food and feed consumption,
      new high-yield varieties with improved quality traits are needed. To ensure the
      safety of the crop, it is important to determine the variation in seed proteins
      along with unintended changes that may occur in the crop as a result various
      stress stimuli, breeding, and genetic modification. Understanding the variation
      of seed proteins in the wild and cultivated soybean cultivars is useful for
      determining unintended protein expression in new varieties of soybeans. Proteomic
      technology is useful to analyze protein variation due to various stimuli. This
      short review discusses transgenic soybeans, different soybean proteins, and the
      approaches used for protein analysis. The characterization of soybean protein
      will be useful for researchers, nutrition professionals, and regulatory agencies
      dealing with soy-derived food products.

PMID- 24099419
TI  - Optically modulatable blue fluorescent proteins.
AB  - Blue fluorescent proteins (BFPs) offer visualization of protein location and
      behavior, but often suffer from high autofluorescent background and poor signal
      discrimination. Through dual-laser excitation of bright and photoinduced dark
      states, mutations to the residues surrounding the BFP chromophore enable long
      wavelength optical modulation of BFP emission. Such dark state engineering
      enables violet-excited blue emission to be increased upon lower energy, green
      coillumination. Turning this green coillumination on and off at a specific
      frequency dynamically modulates collected blue fluorescence without generating
      additional background. Interpreted as transient photoconversion between neutral
      cis and anionic trans chromophoric forms, mutations tune photoisomerization and
      ground state tautomerizations to enable long-wavelength depopulation of the
      millisecond-lived, spectrally shifted dark states. Single mutations to the
      tyrosine-based blue fluorescent protein T203V/S205V exhibit enhanced modulation
      depth and varied frequency. Importantly, analogous single point mutations in the
      nonmodulatable BFP, mKalama1, creates a modulatable variant. Building modulatable
      BFPs offers opportunities for improved BFP signal discrimination vs background,
      greatly enhancing their utility. 

PMID- 24099422
TI  - Chiral Lewis acid catalyzed asymmetric cycloadditions of carbonyl ylides
      generated from diazoimide derivatives and their synthetic applications to
      indolizidine alkaloids.
AB  - Highly enantioselective 1,3-dipolar cycloaddition reactions, catalyzed by chiral
      Lewis acids, between several 3-(2-alkenoyl)-2-oxazolidinones and carbonyl ylides
      that were generated from N-diazoacetyl lactams are described. Reactions of N
      diazoacetyl lactams that possess 5-, 6-, and 7-membered rings were transformed to
      the corresponding epoxy-bridged indolizidines, quinolizidines, and 1
      azabicyclo[5.4.0]undecanes with good to high enantioselectivities. Regio- and
      stereoselective ring-opening of the epoxy-bridged indolizidine cycloadduct gave
      the corresponding alcohol as a single diastereomer. The sequence of asymmetric
      cycloaddition followed by ring-opening was applied to the syntheses of several
      chiral indolizidine derivatives, including (+)-tashiromine. 

PMID- 24099423
TI  - Cellular internalization and mechanism of cytotoxicity of 131I-rituximab in Raji
      cells.
AB  - Rituximab labeled with radioiodine (131I-rituximab) has a large potential to be
      employed for targeted therapy of non-Hodgkin's lymphoma. Studies of parameters
      such as cellular internalization, stability of 131I-rituximab bound to CD20
      receptor of tumor cells, and the mechanism underlying cytotoxicity induced by
      131I-rituximab will be useful for better clinical application. In this article we
      describe the efficacy of 131I-rituximab in CD20-expressing Raji cells. Rituximab
      labeled with 131I was purified on a PD-10 column and characterized using high
      performance liquid chromatography and paper electrophoresis. Raji cells treated
      with 131I-rituximab (1.85 MBq for 2 hours) were washed then incubated. The
      culture medium collected from treated cells showed increased radioactivity over a
      longer period (>6 hours), probably due to the deiodination/degradation of 131I
      rituximab. The tumor cells treated with 131I-rituximab showed time-dependent
      internalization of radioactivity, and at 12 hours the radioactivity was almost
      equally distributed in the membrane and cytoplasm. At 24 hours ~70% of the
      radioactivity was internalized. Cellular toxicity after 131I-rituximab treatment
      showed a time-dependent increase in toxicity as estimated by lactate
      dehydrogenase. Tumor cells treated with 131I-rituximab showed significantly
      higher toxicity and apoptosis compared with the those treated with the same
      concentration of unlabeled rituximab. The increased apoptotic death in cells
      treated with 131I-rituximab was associated with cleavage of poly ADP ribose
      polymerase and upregulation of p53 protein. This study provides a deeper
      understanding about the cellular internalization/stability of 131I-rituximab
      bound to the CD20 receptor and its efficacy in killing Raji cells.

PMID- 24099424
TI  - Algae in the assessment of industrial effluents: case study in Southern Bengal,
      India.
AB  - This article is an assessment of the diversity of scum and bloom algae
      encountered in different industrial effluents of Southern Bengal, India,
      analyzing their habitat and correlating the habitat ecology of each study site.
      The study was conducted during the period May 2009 to August 2010. The study
      sites include effluent release areas of the dairy industry, a distillery unit,
      the leather industry, and an herbal medicine unit. Habitat were analyzed for pH,
      dissolved oxygen, biological oxygen demand, salinity, alkalinity, and phosphate
      and nitrate levels. Correlation coefficients were calculated for habitat
      parameters and algae encountered, showing a significant positive correlation
      between the richness of dominant and subdominant species with biochemical oxygen
      demand and salinity and a significant negative correlation with alkalinity,
      phosphates, and the nitrate-to-phosphate ratio. The richness of dominant and
      subdominant species in the effluent discharge areas show average values of 9 and
      5 in the distillery unit, 8 and 5 in the dairy industry, 7 and 8 in the leather
      industry, and 5 and 9 in the herbal medicine unit, respectively, with a few
      (ranging between 3 and 7) co-occurring species in each case. The algal groups
      encountered were cyanobacteria, euglenophytes, chlorophytes, and
      bacillariophytes, showing Palmer's Algal Pollution Index of 15 in the dairy
      industry, 20 in the distillery unit, 28 in the leather industry, and 8 in the
      herbal medicine unit. 

PMID- 24099425
TI  - Matrix metalloproteinase-9 as a potential tumor marker in breast cancer.
AB  - This study aimed to detect the comparative expression and activity of matrix
      metalloproteinase-9 (MMP-9) and its correlation with known pathological
      parameters such as estrogen receptor, progesterone receptor, and human epidermal
      growth factor receptor 2 (HER2) in 81 malignant breast tumors and adjacent normal
      breast tissues and in blood sera of these patients from different clinical TNM
      stages (ductal carcinoma in situ to T4) of breast cancer. MMP-9 was highly
      expressed in node-positive tumors and the preoperative blood serum of patients,
      but MMP-9 activity was appreciably inhibited in blood serum samples collected
      after surgery. The mature form of MMP-9 (84 kD) was expressed only in clinical
      stage III tumors (T2-4). Appreciable reduction of tissue inhibitor of
      metalloproteinase 1, phosphorylation of epidermal growth factor receptor, and
      translocation of nuclear factor-kappaBeta suggested their possible role in MMP-9
      activation in HER2-positive breast cancer Overexpression and activation of MMP-9
      predicted a higher stage of hormone-sensitive ductal breast carcinoma.
      Downregulation of the endogenous inhibitor of MMP-9, tissue inhibitor of
      metalloproteinase 1, and translocation of the transcription factor nuclear factor
      kappaBeta in tumors may have an appreciable role in the overexpression of MMP-9.
      However, MMP-9 activation was not correlated with expression of estrogen and
      progesterone receptors. Evaluation of MMP-9 expression may provide valuable
      information about breast cancer treatment. 

PMID- 24099426
TI  - Luteolin induces growth arrest in colon cancer cells through involvement of
      Wnt/beta-catenin/GSK-3beta signaling.
AB  - Cancer is a multistep process that typically occurrs over an extended period of
      time, beginning with initiation followed by promotion and progression. Colon
      cancer is the leading cause of morbidity and mortality worldwide. For a variety
      of reasons, patients prefer naturally occurring dietary substances over synthetic
      agents to prevent cancer. Luteolin, a bioflavonoid, possesses antioxidant, anti
      inflammatory, and antiproliferative effects. We analyzed the in vitro anticancer
      and apoptosis-inducing property of luteolin using HCT-15 colon adenocarcinoma
      cells. Cell viability was assessed using trypan blue assay at different
      concentrations. Luteolin at a concentration of 100 uM (IC50) decreased the
      expressions of non-P-beta-catenin, phosphorylated (inactive) glycogen synthase
      kinase-3beta, and cyclin D1 expressions in HCT-15 cells, which were confirmed by
      Western blot analysis. Luteolin also promoted substantial cell cycle arrest at
      the G2/M phase in HCT-15 cells, and it induces apoptosis in HCT-15 cells, as
      revealed by flow cytometric analysis. Furthermore, Western blot analysis showed
      that luteolin treatment enhanced the expression of Bax and caspase-3, whereas the
      expression of Bcl-2 was suppressed. Together, the results of this study revealed
      that luteolin can act as a potent inhibitor of HCT-15 proliferation and can be
      used as an agent against colon cancer.

PMID- 24099427
TI  - Trichosanthes dioica fruit extract ameliorates arsenic-induced brain toxicity in
      male albino rats.
AB  - This study evaluated the ameliorative potential of aqueous extract of
      Trichosanthes dioica fruit (AQTD) against arsenic-induced toxicity in rat brain.
      AQTD (50 and 100 mg/kg) was administered orally to male Wistar albino rats for 20
      consecutive days before oral administration of sodium arsenite (10 mg/kg) for 8
      days. We then evaluated the brain biochemical parameters viz. lipid peroxidation,
      reduced and oxidized glutathione, glutathione-S-transferase, glutathione
      peroxidase, glutathione reductase, superoxide dismutase, catalase, and DNA
      fragmentation. Pretreatment with AQTD significantly and dose dependently
      modulated all the antioxidative parameters and reduced DNA fragmentation in rat
      brain intoxicated with arsenic. These findings conclude that T. dioica fruit
      possesses a remarkable ameliorative effect against arsenic-induced brain toxicity
      in male albino rats, which is mediated by alleviation of arsenic-induced
      oxidative stress by multiple mechanisms. 

PMID- 24099428
TI  - Comparison of free hand versus ultrasound-guided fine needle aspiration of
      thyroid with histopathological correlation.
AB  - Fine-needle aspiration (FNA) cytology of the thyroid is usually performed on an
      outpatient basis. The results of FNA are operator dependent and may be affected
      by the lesion characteristics and the aspiration technique. In current practice
      ultrasound (US) is widely used to guide the needle for aspiration of nondominant
      nodules. Our study aimed to compare the free-hand FNA with US-guided FNA in the
      evaluation of thyroid nodules. A total of 91 cases of thyroid lesions were
      studied at the Department of Pathology, Karnataka Institute of Medical Sciences,
      Hubli, India. All the cases underwent free-hand and US-guided FNA. The
      cytological samples from both procedures were analyzed for adequacy, cytological
      features, and possible diagnosis. The results were correlated with
      histopathological diagnosis whenever possible. Of 91 aspirates, 89 were
      satisfactory and 2 were unsatisfactory on US-guided FNA, whereas 85 were
      satisfactory and 6 were unsatisfactory in free-hand FNA. Of 91 cases 68 (74.7%)
      were nonneoplastic lesions and 21 (23.1%) were neoplastic lesions in US-guided
      FNA, whereas 67 cases (73.6%) were nonneoplastic and 18 cases (19.8%) were
      neoplastic in free-hand FNA. Histopathological study was possible in 25 patients,
      among whom 15 lesions were nonneoplastic and 10 were neoplastic. Sensitivity and
      specificity of US-guided FNA to detect neoplastic lesions were 81.81% and 92.85%,
      respectively, compared with free-hand FNA, for which the sensitivity and
      specificity were 54.54% and 92.85%, respectively. The diagnostic accuracy of
      guided FNA was 88% against the 76% accuracy rate of free-hand FNA. US-guided FNA
      provides a better representative sample and has a higher diagnostic rate in the
      evaluation of thyroid lesions. 

PMID- 24099429
TI  - MNU-induced rat mammary carcinomas: immunohistology and estrogen receptor
      expression.
AB  - Environmental exposure to nitrosamines is associated with the development of
      cancer in a variety of target organs. One such carcinogen, N-methyl-N-nitrosurea
      (MNU), has long been used to induce mammary tumors in rats, which provide a
      useful model to study mammary carcinogenesis. However, some poorly clarified
      issues remain, such as the lack of a clear description of morphological patterns
      of tumors and the distribution and role of estrogen receptors (ERs) during tumor
      progression, as tumors overexpressing ERs show a paradoxical tendency to recur
      after ovariectomy. Mammary carcinomas were induced in Sprague-Dawley rats using
      MNU. The tumors were studied histologically and distribution of smooth muscle
      actin and ERs was studied immunohistochemically. All tumors presented both an
      epithelial and a myoepithelial component, demonstrated by immunohistochemical
      detection of smooth muscle actin. Tumors showed distinct histological patterns:
      well-differentiated papillary and adenoid areas and poorly differentiated solid
      and spindle-cell foci. Overexpression of ERs (>75% of labelled cells vs. 0-75% in
      control tissue) occurred in papillary and adenoid areas but not in solid and
      spindle-cell foci. Poorly differentiated tumor foci are likely to represent a
      more advanced, estrogen-independent phase in cancer progression and constitute
      the basis for tumor recurrence after ovariectomy. 

PMID- 24099430
TI  - A review of molecular mechanisms in the development of hepatocellular carcinoma
      by aflatoxin and hepatitis B and C viruses.
AB  - Aflatoxins are food-borne secondary fungal metabolites that are hepatotoxic,
      hepatocarcinogenic, and mutagenic. Urinary and serum biomarkers are more
      efficient in reflecting dietary exposure to aflatoxin B1 (AFB1) than other
      methods such as food sampling and dietary questionnaires. Chronic infection of
      the hepatitis B virus (HBV) and dietary exposure to AFB1 are the major risk
      factors in a multifactorial etiology of hepatocellular carcinogenesis, raising
      the possibility of a synergistic interaction between 2 agents. These effects are
      due to the formation of DNA and protein adducts and lipid peroxidation. Most
      patients with hepatocellular carcinoma and HBV infection had prevalent GC -> TA
      transversion mutation at the third position of codon 249 of the p53 gene. The HBx
      protein of HBV also promotes cell cycle progression, increases the expression of
      telomerase reverse transcriptase, inactivates negative growth regulators, and
      binds to and inhibits the expression of p53 (antiapoptotic activity) and other
      tumor suppressor genes and senescence-related factors. Some reports also evidence
      the role of hepatitis C virus in the pathogenesis of HCC. Inhibitors of AFB1
      adducts are found to be potent chemoprotective agents against AFB1-induced HCC.
      This review focuses on the interaction of aflatoxin, HBV, and hepatitis C virus
      in the development of HCC.

PMID- 24099431
TI  - Reversal of lead-induced toxicity due to the effect of antioxidants.
AB  - This study was designated to evaluate the protective effect of glutathione (GSH)
      and N-acetyl cysteine (NAC) in reducing the concentration of lead acetate in
      blood and soft tissues (liver, kidney, and brain) and their ability to restore
      altered hematopoietic, hepatic, renal, and other biochemical variables that are
      indicative of tissue oxidative stress in male rats. Male Wistar rats (150 +/- 10
      g) were randomly divided into 6 groups. Group 1 served as control. Group 2 served
      as experimental control was administered lead acetate (50 mg/kg
      intraperitoneally) for 3 days. Group 3 and 4 served as therapeutic controls.
      Animals in groups 5 and 6 received reduced GSH (1 mg/kg intraperitoneally) and
      NAC (50 mg/kg orally) for 3 days after the administration of lead acetate, as in
      group 2. The levels of hepatic and renal markers such as alanine
      aminotransferase, aspartate aminotransferase, triglycerides, cholesterol, urea,
      and uric acid were significantly increased (P <= 0.05) following administration
      of lead acetate. Administration of GSH and NAC provided significant protection to
      thiobarbituric acid reactive substances levels and reduced GSH content in
      tissues. On the other hand, significant recovery in lead-sensitive biochemical
      indices, like delta-aminolevulinic acid dehydratase, delta-aminolevulinic acid,
      and lead concentration in blood and soft tissues also were observed. It was
      concluded that NAC provided maximum protection compared with reduced GSH.

PMID- 24099432
TI  - Indicated cognitive behavioral group depression prevention compared to
      bibliotherapy and brochure control: acute effects of an effectiveness trial with
      adolescents.
AB  - OBJECTIVE: We tested whether a brief cognitive behavioral (CB) group and
      bibliotherapy prevention reduce major depressive disorder (MDD) onset, depressive
      symptoms, and secondary outcomes relative to brochure controls in adolescents
      with self-reported depressive symptoms when school personnel recruit participants
      and deliver the intervention. METHOD: Three hundred seventy-eight adolescents (M
      age = 15.5 years, SD = 1.2; 68% female, 72% White) with elevated self-assessed
      depressive symptoms were randomized to a 6-session CB group, minimal contact CB
      bibliotherapy, or educational brochure control. Participants were assessed at
      pretest, posttest, and 6-month follow-up. RESULTS: CB group participants showed a
      significantly lower risk for major depressive disorder onset (0.8%), compared to
      both CB bibliotherapy (6.3%) and brochure control (6.5%; hazard ratio = 8.1 and
      8.3, respectively). Planned contrasts indicated that CB group resulted in lower
      depressive symptom severity than brochure control at posttest (p = .03, d = 0.29)
      but not 6-month follow-up; differences between CB group and bibliotherapy were
      nonsignificant at posttest and 6-month follow-up. Condition effects were
      nonsignificant for social adjustment and substance use. CONCLUSIONS: The finding
      that a brief CB group intervention delivered by real-world providers
      significantly reduced MDD onset relative to both brochure control and
      bibliotherapy is very encouraging, although effects on continuous outcome
      measures were small or nonsignificant and approximately half the magnitude of
      those found in efficacy research, potentially because the present sample reported
      lower initial depression.

PMID- 24099433
TI  - Lay counselors' ability to deliver counseling for behavior change.
AB  - OBJECTIVE: Options for Health is an evidence-based sexual risk reduction
      intervention based on motivational interviewing (MI). Thirty-nine antiretroviral
      adherence lay counselors were trained to deliver Options for Health to help their
      patients to optimize their antiretroviral treatment adherence. An evaluation of
      counselors' ability to deliver the intervention after 35 hr of training revealed
      that counselors struggled with elements of the 8-step Options protocol and failed
      to achieve proficiency in MI. The current study aimed to determine the impact of
      refresher training and supervision on counselors' proficiency in the
      intervention. METHOD: Audio-recordings of counseling sessions were collected for
      22 of 39 counselors after 18 hr of refresher training and supervision had been
      delivered over a 12-month period. Recordings were transcribed, translated, and
      analyzed for fidelity to the Options protocol and the MI approach. Analysis was
      conducted using the Motivational Interviewing Treatment Integrity Tool and an
      instrument developed by the researchers. Results were compared to findings from
      an evaluation of counselors' performance immediately following the initial 35-hr
      training. RESULTS: Counselors improved their delivery of some intervention steps,
      but not others; their use of micro-counseling skills and therapeutic approach
      improved to such an extent that they closely approximated the MI approach.
      CONCLUSIONS: This study contributes evidence for the positive impact of ongoing
      training and supervision on lay health worker practice. Although counselors did
      not achieve complete proficiency in the Options protocol, refresher training and
      supervision improved counselors' basic counseling communication skills and
      therapeutic approach, enabling them to deliver better quality counseling for
      behavior change.

PMID- 24099434
TI  - On sepsis, troponin and vasopressin: the bitter truth.
AB  - One of the rationales for the use of vasopressin in septic shock has been its
      potential cardioprotective mechanisms. Lower heart rates, higher arterial
      pressures, and fewer norepinephrine doses during vasopressin therapy were
      hypothesized to protect the heart from myocardial ischemia. In a prospective sub
      study of the VASST (Vasopressin in Septic Shock Trial) project, Mehta and
      colleagues specifically evaluated this hypothesis but failed to find lower
      cardiac biomarkers or fewer ischemic electrocardiogram changes in patients
      receiving vasopressin compared with subjects receiving norepinephrine alone.
      After recent evidence of a lacking survival benefit, the present study results
      further challenge the future role of vasopressin as a vasopressor in septic
      shock. 

PMID- 24099435
TI  - A tribute to Professor Harold H. Messer on his retirement.

PMID- 24099436
TI  - Clinical features of patients with stress-induced cardiomyopathy associated with
      renal dysfunction: 7 case series in single center.
AB  - BACKGROUND: Stress-induced cardiomyopathy (sCMP) is characterized by transient
      wall-motion abnormalities involving the left ventricular apex and mid-ventricle
      that are precipitated by emotional or physical stress. As the heart and kidney
      influence each other's function through bidirectional pathways, sCMP can induce
      renal dysfunction or be induced by renal dysfunction. This study reviewed the
      clinical characteristics and outcomes of patients with confirmed sCMP associated
      with renal dysfunction. METHODS: We conducted a retrospective analysis of the
      medical records of all patients from our institution who were diagnosed with sCMP
      from March 2010 to April 2012. Each patient's demographic characteristics,
      presenting symptoms, triggering events, electrocardiographic characteristics,
      laboratory data, echocardiographic study findings, cardiac catheterization data,
      and outcomes were reviewed. RESULTS: Among 30 patients who were diagnosed with
      sCMP, 7 patients had associated renal dysfunction. Three patients were on
      maintenance hemodialysis (HD) and 4 patients had acute kidney injury (AKI). Their
      mean ejection fraction was 35.2% at initial echocardiography, and 57.2% at follow
      up echocardiography. Pericardial effusion was detected in all HD patients
      initially; these patients were treated with intensive HD for suspected under
      dialysis status. In patients with AKI, the mean peak serum creatinine was 4.17
      mg/dL. Two patients were treated with continuous renal replacement therapy. One
      patient required maintenance HD, and 1 patient died. Two patients had full renal
      recovery to their baseline renal function at 7 and 14 days. CONCLUSIONS: Patients
      with renal dysfunction including those with AKI and those undergoing HD can
      develop sCMP, renal function must be closely monitored in patients with sCMP.
      Additionally, it should be considered that patients on HD who develop sCMP may be
      under-dialyzed.

PMID- 24099437
TI  - Monitoring the immune response to vaccination with an inactivated vaccine
      associated to bovine neonatal pancytopenia by deep sequencing transcriptome
      analysis in cattle.
AB  - Bovine neonatal pancytopenia (BNP) is a new fatal, alloimmune/alloantibody
      mediated disease of new-born calves induced by ingestion of colostrum from cows,
      which had been vaccinated with a specific vaccine against the Bovine Virus
      Diarrhoea Virus (BVDV). The hypothesis of pathogenic MHC class I molecules in the
      vaccine had been put up, but no formal proof of specific causal MHC class I
      alleles has been provided yet. However, the unique features of the vaccine
      obviously result in extremely high specific antibody titres in the vaccinated
      animals, but apparently also in further molecules inducing BNP. Thus, a
      comprehensive picture of the immune response to the vaccine is essential.
      Applying the novel approach of next generation RNA sequencing (RNAseq), our study
      provides a new holistic, comprehensive analysis of the blood transcriptome
      regulation after vaccination with the specific BVDV vaccine. Our RNAseq approach
      identified a novel cytokine-like gene in the bovine genome that is highly
      upregulated after vaccination. This gene has never been described before in any
      other species and might be specific to ruminant immune response. Furthermore, our
      data revealed a very coordinated immune response to double-stranded (ds) RNA or a
      dsRNA analogue after vaccination with the inactivated single-stranded (ss) RNA
      vaccine. This would suggest either a substantial contamination of the vaccine
      with dsRNA from host cells after virus culture or a dsRNA analogue applied to the
      vaccine. The first option would highlight the potential risks associated with
      virus culture on homologous cells during vaccine production; the latter option
      would emphasise the potential risks associated with immune stimulating adjuvants
      used in vaccine production. 

PMID- 24099439
TI  - Photo-biohydrogen production potential of Rhodobacter capsulatus-PK from wheat
      straw.
AB  - BACKGROUND: Biotechnological exploitation of lignocellulosic biomass is promising
      for sustainable and environmentally sound energy provision strategy because of
      the abundant availability of the renewable resources. Wheat straw (WS) comprising
      of 75-80% cellulose and hemicellulose is one of widely available, inexpensive and
      renewable lignocellulosic biomass types. The cellulosic and hemicellulose
      substrate can be hydrolyzed into monomeric sugars by chemical and/or biological
      methods. RESULTS: This study examined comparative potential of dilute acid and
      pre-ammonia pretreated and enzymatically hydrolyzed wheat straw (WS) for hydrogen
      production by purple non sulfur bacterium Rhodobacter capsulatus-PK. Gas
      production became noticeable after 14 h of inoculation in WS pretreated with 4%
      H2SO4. The detoxified liquid hydrolyzate (DLH) after overliming attained a
      production level of 372 mL-H2/L after 16 h under illumination of 120-150 W/m2 at
      30 +/- 2.0 degrees C. Whereas the non-detoxified acid pretreated hydrolyzate
      (NDLH) of WS could produce only upto 254 mL-H2/L after 21 h post inoculation.
      Evolution of H2 became observable just after 10 +/- 2.0 h of inoculation by
      employing 48 h age inoculum on the WS pretreated with 30% ammonia, hydrolyzed
      with cellulase 80 FPU/g and beta-glucosidase 220 CbU/ml at 50 degrees C. Upto 712
      ml/L of culture was measured with continuous shaking for 24 h. The 47.5% and
      64.2% higher hydrogen volume than the DLH and NDLH substrates, respectively
      appeared as a function of significantly higher monomeric sugar contents of the
      enzymatically hydrolyzed substrate and lesser/zero amounts of toxic derivatives
      including pH reducing agents. CONCLUSION: Photofermentative hydrogen production
      from lignocellulosic waste is a feasible approach for eco-friendly sustainable
      supply of bioenergy in a cost-effective way. Results of this study provide new
      insight for addressing biotechnological exploitation of abundantly available and
      low-cost cellulosic substrates.

PMID- 24099438
TI  - Comparison of renal ischemic damage during laparoscopic partial nephrectomy with
      artery-vein and artery-only clamping.
AB  - OBJECTIVE: To compare renal ischemic damage caused by artery-only (AO) and artery
      vein (AV) clamping after laparoscopic partial nephrectomy. MATERIALS AND METHODS:
      We included 58 patients who underwent laparoscopic partial nephrectomy for
      nonhilar exophytic renal tumors in this study. AV clamping was used for 26 of
      these patients, while AO clamping was used for 32. All patients had a functional
      contralateral kidney. We assessed effective renal plasma flow (ERPF) by
      (99m)Technetium-mercaptoacetyltriglycine ((99m)Tc-MAG3) renal scintigraphy
      preoperatively and at 1 week and 6 months postoperatively. In addition, we
      analyzed (99m)Tc-MAG3 uptake regionally in the surgically nonaffected areas.
      RESULTS: Mean tumor diameters were 3.0 cm in the AV group and 2.8 cm in the AO
      group. Warm ischemic time was significantly shorter in the AV group than the AO
      group (26.3 vs. 30.7 minutes, respectively, p=0.007). There were no differences
      in the estimated glomerular filtration rates or ERPF of the operated kidney
      between groups preoperatively or 1 week or 6 months postoperatively. The decrease
      in regional (99m)Tc-MAG3 uptake of the operated kidney at 1 week was correlated
      with warm ischemic time in both groups, being stronger in the AV group (p<0.001)
      than in the AO group (p=0.027). This decrease was significantly less in the AO
      group when the ischemic time was >=25 minutes (88.1% vs. 102.5%, p=0.001).
      CONCLUSIONS: Ischemic renal damage during laparoscopic partial nephrectomy was
      lessened by applying AO clamping particularly in cases with prolonged ischemic
      time.

PMID- 24099440
TI  - Photoisomerization-induced manipulation of single-electron tunneling for novel Si
      based optical memory.
AB  - We demonstrated optical manipulation of single-electron tunneling (SET) by
      photoisomerization of diarylethene molecules in a metal-insulator-semiconductor
      (MIS) structure. Stress is placed on the fact that device operation is realized
      in the practical device configuration of MIS structure and that it is not
      achieved in structures based on nanogap electrodes and scanning probe techniques.
      Namely, this is a basic memory device configuration that has the potential for
      large-scale integration. In our device, the threshold voltage of SET was clearly
      modulated as a reversible change in the molecular orbital induced by
      photoisomerization, indicating that diarylethene molecules worked as optically
      controllable quantum dots. These findings will allow the integration of photonic
      functionality into current Si-based memory devices, which is a unique feature of
      organic molecules that is unobtainable with inorganic materials. Our proposed
      device therefore has enormous potential for providing a breakthrough in Si
      technology. 

PMID- 24099441
TI  - Isthmocele.

PMID- 24099442
TI  - Changing the future: social responsibilities.

PMID- 24099443
TI  - Association between physical activity in early pregnancy and markers of placental
      growth and function.
AB  - OBJECTIVES: It has been suggested that physical activity (PA) can influence the
      development of the placenta and the risk of placenta-mediated complications of
      pregnancy. We evaluated the association between PA and early markers of placental
      development. METHODS: Ninety-four nulliparous women were invited to participate
      in a prospective observational cohort study. Assessment included measurement of
      placental growth factor (PlGF) and pregnancy-associated plasma protein-A (PAPP-A)
      concentrations (expressed in multiples of the median), an ultrasound at 11 to 13
      weeks for measurement of placental volume and the mean uterine artery (UtA)
      pulsatility index, and a questionnaire on PA. The association between PA and
      these markers was evaluated using univariate and multivariate regression
      analyses. RESULTS: We found a significantly lower concentration of PlGF and a
      trend towards lower placenta volume and lower PAPP-A concentration with increased
      PA frequency. The negative association between PA frequency and PlGF
      concentration remained significant after adjustment for potential confounding
      factors. CONCLUSION: Our results suggest that PA in early pregnancy could
      negatively affect placental development. This finding could explain the
      association between PA and severe preeclampsia. This finding deserves
      confirmation in a larger cohort.

PMID- 24099444
TI  - Predicting preterm birth in twin pregnancy: was the previous birth preterm? A
      Canadian experience.
AB  - OBJECTIVE: Most studies determining risk of preterm birth in a twin pregnancy
      subsequent to a previous preterm birth are based on linkage studies or small
      sample size. We wished to identify recurrent risk factors in a cohort of mothers
      with a twin pregnancy, eliminating all known confounders. METHODS: We conducted a
      retrospective cohort study of twin births at a tertiary care centre in Montreal,
      Quebec, between 1994 and 2008, extracting information, including chorionicity,
      from patient charts. To avoid the effect of confounding factors, we included only
      women with a preceding singleton pregnancy and excluded twin-to-twin transfusion
      syndrome, fetal chromosomal/structural anomalies, fetal demise, and preterm
      iatrogenic delivery for reasons not encountered in both pregnancies. We used
      multiple regression and sensitivity analyses to determine recurrent risk factors.
      RESULTS: Of 1474 twin pregnancies, 576 met the inclusion criteria. Of these, 309
      (53.6%) delivered before 37 weeks. Preterm birth in twins was strongly associated
      with preterm birth of the preceding singleton (adjusted OR 3.23; 95% CI 1.75 to
      5.98). The only other risk factors were monochorionic twins (adjusted OR 1.82;
      95% CI 1.21 to 2.73) and oldest or youngest maternal ages. Chronic or gestational
      hypertension, preeclampsia, and insulin-dependent diabetes during the singleton
      pregnancy did not significantly affect risk. CONCLUSION: Preterm birth in a
      previous singleton pregnancy was confirmed as an independent risk factor for
      preterm birth in a subsequent twin pregnancy. This three-fold increase in risk
      remained stable regardless of year of birth, inclusion/exclusion of pregnancies
      following assisted reproduction, or defining preterm birth as < 34 or < 37 weeks'
      gestational age. Until the advent of optimal preventive strategies, close
      obstetric surveillance of twin pregnancies is warranted.

PMID- 24099445
TI  - Assessing the accuracy of pregnant women in recalling pre-pregnancy weight and
      gestational weight gain.
AB  - OBJECTIVE: Maternity care providers can use pre-pregnancy weight (PPW) and
      gestational weight gain (GWG) as markers for difficult delivery, and frequently
      obtain this information directly from the patient. The goal of this study was to
      determine whether women report their PPW and GWG correctly at the end of
      pregnancy. METHODS: We performed a prospective cohort study of 189 women
      delivering between June 1, 2011, and July 31, 2011, at the Saint John Regional
      Hospital or the Moncton Hospital in New Brunswick. Self- reported PPW and GWG
      were compared with measured weights obtained from the antenatal chart and upon
      presentation for delivery. Patient characteristics, BMI classification, and
      accuracy and degree of error in recall were assessed. RESULTS: The majority of
      respondents were under 30 years of age (63.4%) and were delivering at term
      (96.3%). Ninety women (47.6%) were having their first baby. A record of weight
      measured in the first trimester was available for 98 respondents (51.9%); using
      this information, 44 women (44.9%) were determined to be overweight or obese at
      delivery. Approximately one third of women with a normal BMI were not able to
      recall their PPW or GWG accurately (+/- 1 kg). Among all BMI classes, there was a
      consistent pattern of under-reporting of PPW (by a mean of 1.52 kg) and over
      reporting of GWG (by a mean of 1.61 kg), but several extreme outliers were
      identified. CONCLUSION: At the time of delivery, under-reporting of PPW and over
      reporting of GWG are common and difficult to predict. Maternity care providers
      should be aware of this discrepant reporting of PPW and GWG and recognize the
      implications for intrapartum management and postpartum weight loss.

PMID- 24099446
TI  - Use of glycated hemoglobin and waist circumference for diabetic screening in
      women with a history of gestational diabetes.
AB  - OBJECTIVE: Although their risk of type 2 diabetes is markedly increased, women
      with prior gestational diabetes mellitus (GDM) do not receive appropriate testing
      following their pregnancy. Identifying a less burdensome testing method might
      increase postpartum testing rates. Our objective was to examine the adequacy of
      glycated hemoglobin (A1C) and waist circumference (WC) measurements to detect
      impaired glucose metabolism among women with prior GDM. METHODS: The analysis
      included 178 women who had GDM between 2003 and 2010. WC and A1C were measured,
      and a 75g 2h-OGTT was performed. Pre-diabetes was defined as a fasting plasma
      glucose (FPG) >= 5.6 and < 7.0 mmol/L or a 2-hour plasma glucose (2h-PG) >= 7.8
      and < 11.0 mmol/L, and type 2 diabetes was defined as a FPG >= 7.0 mmol/L and/or
      a 2h-PG >= 11.1 mmol/L. Sensitivity and specificity analyses were performed.
      RESULTS: The mean age of subjects was 36.4 +/- 4.8 years, and testing occurred at
      a mean 3.5 +/- 1.9 years following delivery. Combining A1C >= 5.7% and WC >= 88
      cm to detect pre-diabetes had a sensitivity of 76% and specificity of 62%, and to
      detect type 2 diabetes it had a sensitivity of 91% and specificity of 34%.
      Compared with women who had A1C and WC within the normal range, women with A1C >=
      5.7% and WC >= 88 cm were more likely to have type 2 diabetes (OR 4.4; 95% CI 2.0
      to 9.9). CONCLUSION: These analyses suggest that the combination of A1C and WC
      could represent a sensitive test for pre-diabetes and type 2 diabetes in the
      years following a pregnancy complicated by GDM. Further validation of this
      testing method is required.

PMID- 24099447
TI  - Brain metastases in women with epithelial ovarian cancer: multimodal treatment
      including surgery or gamma-knife radiation is associated with prolonged survival.
AB  - OBJECTIVE: To explore the impact of treatment modality on survival in patients
      with brain metastases from epithelial ovarian cancer. METHODS: We conducted a
      retrospective review of cases of ovarian cancer with brain metastases treated at
      institutions in three countries (Canada, China, and India) and conducted a search
      for studies regarding brain metastases in ovarian cancer reporting survival
      related to treatment modality. Survival was analyzed according to treatment
      regimens involving (1) some form of surgical excision or gamma-knife radiation
      with or without other modalities, (2) other modalities without surgery or gamma
      knife radiation, or (3) palliation only. RESULTS: Twelve patients (mean age 56
      years) with detailed treatment/outcome data were included; five were from China,
      four from Canada, and three from India. Median time from diagnosis of ovarian
      cancer to brain metastasis was 19 months (range 10 to 37 months), and overall
      median survival time from diagnosis of ovarian cancer was 38 months (13 to 82
      months). Median survival time from diagnosis of brain metastasis was 17 months (1
      to 45 months). Among patients who had multimodal treatment including gamma-knife
      radiotherapy or surgical excision, the median survival time after the
      identification of brain metastasis was 25.6 months, compared with 6.0 months in
      patients whose treatment did not include this type of focused localized modality
      (P = 0.006). Analysis of 20 studies also indicated that use of gamma-knife
      radiotherapy and excisional surgery in multi-modal treatment resulted in improved
      median survival interval (25 months vs. 6.0 months, P < 0.001). CONCLUSION: In
      the subset of patients with brain metastases from ovarian cancer, prolonged
      survival may result from use of multidisciplinary therapy, particularly if
      metastases are amenable to localized treatments such as gamma-knife radiotherapy
      and surgical excision.

PMID- 24099448
TI  - Fibroid infected with Escherichia coli requiring surgical removal following
      uterine artery embolization.
AB  - BACKGROUND: Uterine fibroid necrosis and infection is a rare but potentially
      serious event following uterine artery embolization (UAE). We describe a case of
      surgical removal of an infected necrotic uterine fibroid. CASE: A 31-year-old
      Jehovah's Witness with severe anemia presented with sepsis following UAE. The
      uterus was preserved by performing transvaginal surgical removal. Final pathology
      demonstrated Escherichia Coli infection of the necrotic fibroid. The patient
      improved postoperatively. CONCLUSION: Surgical removal of an infected necrotic
      fibroid may be a preferred option for women wishing to avoid hysterectomy
      following UAE. Appropriate case selection and optimization of hemoglobin
      concentration before UAE is important to minimize complications.

PMID- 24099449
TI  - Lymphangioma of the vagina.
AB  - BACKGROUND: Vaginal lymphangioma is an extremely rare lesion. Lymphangioma in
      other areas is usually asymptomatic, and bleeding is a common complication and
      presentation. CASE: We describe the identification of a vaginal lymphangioma in a
      47-year-old woman and discuss the histopathology, diagnosis, and management,
      based on colposcopy and histology results. CONCLUSION: Vaginal lymphangioma
      should be identified by histopathology to exclude other malignant tumours in the
      vagina and to plan appropriate therapy.

PMID- 24099450
TI  - The Maternal Health Clinic: a new window of opportunity for early heart disease
      risk screening and intervention for women with pregnancy complications.

PMID- 24099452
TI  - Far-infrared spectrum of S(CN)2 measured with synchrotron radiation: global
      analysis of the available high-resolution spectroscopic data.
AB  - The high resolution Fourier transform spectrum of the chemically challenging
      sulfur dicyanide, S(CN)2, molecule was recorded at the far-infrared beamline of
      the synchrotron at the Canadian Light Source. The spectrum covered 50-350 cm(-1),
      and transitions in three fundamentals, nu4, nu7, and nu8, as well as in the hot
      band sequence (n + 1)nu4 - nnu4, n = 1-4, have been assigned and measured. Global
      analysis of over 21,300 pure rotation and rotation vibration transitions allowed
      determination of precise energies for 12 of the lowest vibrationally excited
      states of S(CN)2, including the five lowest fundamentals. These results
      constitute an extensive set of benchmarks for ab initio anharmonic force field
      calculations and the observed and calculated vibration-rotation constants and
      anharmonic frequencies are compared. The semiexperimental equilibrium, r(e)(SE),
      geometry of S(CN)2 has also been evaluated. In the course of the measurements,
      new information concerning the physical chemistry of S(CN)2 has been obtained.

PMID- 24099451
TI  - Induction of labour.
AB  - OBJECTIVE: To review the most current literature in order to provide evidence
      based recommendations to obstetrical care providers on induction of labour.
      OPTIONS: Intervention in a pregnancy with induction of labour. OUTCOMES:
      Appropriate timing and method of induction, appropriate mode of delivery, and
      optimal maternal and perinatal outcomes. EVIDENCE: Published literature was
      retrieved through searches of PubMed, CINAHL, and The Cochrane Library in 2010
      using appropriate controlled vocabulary (e.g., labour, induced, labour induction,
      cervical ripening) and key words (e.g., induce, induction, augmentation). Results
      were restricted to systematic reviews, randomized control trials/controlled
      clinical trials, and observational studies. There were no date or language
      restrictions. Searches were updated on a regular basis and incorporated in the
      guideline to the end of 2010. Grey (unpublished) literature was identified
      through searching the websites of health technology assessment and health
      technology-related agencies, clinical practice guideline collections, clinical
      trial registries, and national and international medical specialty societies.
      VALUES: The evidence in this document was rated using criteria described in the
      Report of the Canadian Task Force on Preventative Health Care (Table 1). SUMMARY
      STATEMENTS: 1. Prostaglandins E(2) (cervical and vaginal) are effective agents of
      cervical ripening and induction of labour for an unfavourable cervix. (I) 2.
      Intravaginal prostaglandins E(2) are preferred to intracervical prostaglandins
      E(2) because they results in more timely vaginal deliveries. (I).

PMID- 24099453
TI  - Changes in behavior and hematological parameters of freshwater African catfish
      Clarias gariepinus (Burchell 1822) following sublethal exposure to
      chloramphenicol.
AB  - The present study was aimed at evaluating the effects of different concentrations
      of the most commonly used fish antimicrobial drug, chloramphenicol (CAP), on the
      behavior and hematological parameters of Clarias gariepinus. Fish specimens were
      exposed to three (2.5, 5.0 and 10.0 mg L(-1)) sublethal concentrations of CAP and
      a control. Abnormal behavioral changes were observed in fish exposed to higher
      concentration of CAP. Blood erythrocytes were sampled on days 1, 5, 10 and 15
      postexposure to evaluate hematological parameters. Results showed concentration-
      and time-dependent significant increase in packed cell volume after day 5 of
      exposure (p < 0.05). Hemoglobin values also significantly decreased from day 5,
      whereas values of mean cellular volume significantly decreased throughout the
      experimental period (p < 0.05). A mixed trend was observed in the mean values of
      red blood cells, white blood cells, mean cellular hemoglobin and mean cellular
      hemoglobin concentration as well as neutrophils. Activities of lymphocytes were
      significantly increased in all CAP-treated fish during the exposure period,
      whereas no significant differences were observed in values of monocytes,
      eosinophils and basophils among the treatment groups and control. Consequently,
      precautions must be taken, especially when high concentrations of CAP are used in
      long-term treatments of C. gariepinus in aquaculture.

PMID- 24099454
TI  - Chemical composition, antimicrobial and antioxidant activity of the essential
      oils from Pimpinellatragium Vill. subsp. glauca (C. Presl.) C. Brullo & Brullo
      (Apiaceae) growing wild in Sicily.
AB  - The essential oils from flowers, leaves and stems hydrodistilled from Pimpinella
      tragium Vill, subsp. glauca were characterised by GC and gas chromatography-mass
      spectrometry analysis. The C-12 nor-sesquiterpenes are the principal class of
      metabolites (56.6-70.6%) among which geijerene (28.9/49.3%) and pregeijerene
      (10/19.1%) predominate. Antimicrobial and antioxidant activities were evaluated.
      The minimum inhibitory concentration values indicate that oil obtained from the
      stems is the most active for antimicrobial activities and the sample with the
      biggest antioxidant capacity is the flower oil.

PMID- 24099456
TI  - Three-dimensional atomic force microscopy: interaction force vector by direct
      observation of tip trajectory.
AB  - The prospect of a robust three-dimensional atomic force microscope (AFM) holds
      significant promise in nanoscience. Yet, in conventional AFM, the tip-sample
      interaction force vector is not directly accessible. We scatter a focused laser
      directly off an AFM tip apex to rapidly and precisely measure the tapping tip
      trajectory in three-dimensional space. This data also yields three-dimensional
      cantilever spring constants, effective masses, and hence, the tip-sample
      interaction force components via Newton's second law. Significant lateral forces
      representing 49 and 13% of the normal force (Fz = 152 +/- 17 pN) were observed in
      common tapping mode conditions as a silicon tip intermittently contacted a glass
      substrate in aqueous solution; as a consequence, the direction of the force
      vector tilted considerably more than expected. When addressing the surface of a
      lipid bilayer, the behavior of the force components differed significantly from
      that observed on glass. This is attributed to the lateral mobility of the lipid
      membrane coupled with its elastic properties. Direct access to interaction
      components Fx, Fy, and Fz provides a more complete view of tip dynamics that
      underlie force microscope operation and can form the foundation of a three
      dimensional AFM in a plurality of conditions. 

PMID- 24099455
TI  - Obstructive jaundice due to ampullary metastasis of renal cell carcinoma.
AB  - Renal cell carcinoma is often characterized by the presence of metachronous
      metastases in unusual sites. The presence of isolated metastases is treated with
      surgical excision with good anticipated results. On the other hand, systemic
      chemotherapy is administered in the context of metastatic spread, usually sunitib
      or sorafenib. In such cases, however, the presence of symptomatic foci calls for
      minimal intervention.We present a case of a 77-year-old patient who presented
      with obstructive jaundice due to an ampullary mass. Endoscopic excision and
      biopsy set the diagnosis of metastatic renal cell carcinoma. Consequently,
      imaging studies revealed the presence of multiple foci in the lungs and bone.
      Therefore, pancreatoduodenectomy was excluded and the patient underwent
      endoscopic ampullectomy and was set to oral sunitinib. Interestingly, despite
      generalized spread, local control was achieved until the patient succumbed to
      carcinomatosis.Painless obstructive jaundice in a patient with history of renal
      cancer and negative computed tomography scanning for pancreatic or other causes
      of obstruction should alert for prompt investigation for an ampullary metastasis.

PMID- 24099457
TI  - Deployment-related sequelae and treatment utilization in rural and urban war
      veterans in Hawaii.
AB  - This study compared common deployment-related health issues and correlates of
      mental health service utilization among rural and urban veterans of Operation
      Enduring Freedom (OEF), Operation Iraqi Freedom (OIF), and Operation New Dawn
      (OND) living in Hawaii. Frequency of utilization of a broad range of mental
      health resources, including clergy/spiritual leaders, videoconference/online
      programs, and traditional/alternative healers, was also characterized. A random
      sample of 116 rural and 117 urban ethnoracially diverse veterans completed a mail
      survey. Rural veterans were more likely than urban veterans to meet screening
      criteria for posttraumatic stress disorder (PTSD), deployment-related concussion
      with persistent postconcussive symptoms, and alcohol use problems. Over one third
      of veterans who desired help for a mental health problem reported no current use
      of any services. Rural veterans were more likely than urban veterans to have
      accessed Veteran Readjustment Centers, but they did not differ with respect to
      utilization of other services. Correlates of mental health service utilization
      included higher education, PTSD, and lower mental-health-related quality of life.
      Results of this study underscore the need for dissemination efforts to enable
      OEF/OIF/OND veterans to access mental health resources.

PMID- 24099458
TI  - Acceptance of mental illness: core components of a multifaceted construct.
AB  - The recovery movement has identified acceptance of mental illness as critical to
      quality of life and illness management. However, there is a general lack of
      research on the acceptance of mental illness. The present qualitative study was
      conducted with 30 participants with mental illness to clarify the construct of
      acceptance. Grounded theory methodology is utilized to analyze the 30
      semistructured interviews. Results in the present study reveal acceptance to be a
      multifaceted construct composed of several core characteristics, including the:
      (1) identity component, (2) cognitive component, (3) emotional component, (4)
      behavioral component, and (5) relational component. In addition, when asked to
      define acceptance of mental illness, some participants noted negative
      connotations to acceptance. Implications for psychological services and future
      research will be discussed to guide additional study and practice in this area.

PMID- 24099459
TI  - Novel applications of motif-directed profiling to identify disease resistance
      genes in plants.
AB  - BACKGROUND: Molecular profiling of gene families is a versatile tool to study
      diversity between individual genomes in sexual crosses and germplasm. Nucleotide
      binding site (NBS) profiling, in particular, targets conserved nucleotide binding
      site-encoding sequences of resistance gene analogs (RGAs), and is widely used to
      identify molecular markers for disease resistance (R) genes. RESULTS: In this
      study, we used NBS profiling to identify genome-wide locations of RGA clusters in
      the genome of potato clone RH. Positions of RGAs in the potato RH and DM genomes
      that were generated using profiling and genome sequencing, respectively, were
      compared. Largely overlapping results, but also interesting discrepancies, were
      found. Due to the clustering of RGAs, several parts of the genome are overexposed
      while others remain underexposed using NBS profiling. It is shown how the
      profiling of other gene families, i.e. protein kinases and different protein
      domain-coding sequences (i.e., TIR), can be used to achieve a better marker
      distribution. The power of profiling techniques is further illustrated using RGA
      cluster-directed profiling in a population of Solanum berthaultii. Multiple
      different paralogous RGAs within the Rpi-ber cluster could be genetically
      distinguished. Finally, an adaptation of the profiling protocol was made that
      allowed the parallel sequencing of profiling fragments using next generation
      sequencing. The types of RGAs that were tagged in this next-generation profiling
      approach largely overlapped with classical gel-based profiling. As a potential
      application of next-generation profiling, we showed how the R gene family
      associated with late blight resistance in the SH*RH population could be
      identified using a bulked segregant approach. CONCLUSIONS: In this study, we
      provide a comprehensive overview of previously described and novel profiling
      primers and their genomic targets in potato through genetic mapping and
      comparative genomics. Furthermore, it is shown how genome-wide or fine mapping
      can be pursued by choosing different sets of profiling primers. A protocol for
      next-generation profiling is provided and will form the basis for novel
      applications. Using the current overview of genomic targets, a rational choice
      can be made for profiling primers to be employed.

PMID- 24099460
TI  - Development of an informatics platform for therapeutic protein and peptide
      analytics.
AB  - The momentum gained by research on biologics has not been met yet with equal
      thrust on the informatics side. There is a noticeable lack of software for data
      management that empowers the bench scientists working on the development of
      biologic therapeutics. SARvision|Biologics is a tool to analyze data associated
      with biopolymers, including peptides, antibodies, and protein therapeutics
      programs. The program brings under a single user interface tools to filter, mine,
      and visualize data as well as those algorithms needed to organize sequences. As
      part of the data-analysis tools, we introduce two new concepts: mutation cliffs
      and invariant maps. Invariant maps show the variability of properties when a
      monomer is maintained constant in a position of the biopolymer. Mutation cliff
      maps draw attention to pairs of sequences where a single or limited number of
      point mutations elicit a large change in a property of interest. We illustrate
      the program and its applications using a peptide data set collected from the
      literature. 

PMID- 24099461
TI  - Construction of an in vitro bypassed pyruvate decarboxylation pathway using
      thermostable enzyme modules and its application to N-acetylglutamate production.
AB  - BACKGROUND: Metabolic engineering has emerged as a practical alternative to
      conventional chemical conversion particularly in biocommodity production
      processes. However, this approach is often hampered by as yet unidentified
      inherent mechanisms of natural metabolism. One of the possible solutions for the
      elimination of the negative effects of natural regulatory mechanisms on
      artificially engineered metabolic pathway is to construct an in vitro pathway
      using a limited number of enzymes. Employment of thermostable enzymes as
      biocatalytic modules for pathway construction enables the one-step preparation of
      catalytic units with excellent selectivity and operational stability. Acetyl-CoA
      is a central precursor involved in the biosynthesis of various metabolites. In
      this study, an in vitro pathway to convert pyruvate to acetyl-CoA was constructed
      and applied to N-acetylglutamate production. RESULTS: A bypassed pyruvate
      decarboxylation pathway, through which pyruvate can be converted to acetyl-CoA,
      was constructed by using a coupled enzyme system consisting of pyruvate
      decarboxylase from Acetobacter pasteurianus and the CoA-acylating aldehyde
      dehydrogenase from Thermus thermophilus. To demonstrate the applicability of the
      bypassed pathway for chemical production, a cofactor-balanced and CoA-recycling
      synthetic pathway for N-acetylglutamate production was designed by coupling the
      bypassed pathway with the glutamate dehydrogenase from T. thermophilus and N
      acetylglutamate synthase from Thermotoga maritima. N-Acetylglutamate could be
      produced from an equimolar mixture of pyruvate and alpha-ketoglutarate with a
      molar yield of 55% through the synthetic pathway consisting of a mixture of four
      recombinant E. coli strains having either one of the thermostable enzymes. The
      overall recycling number of CoA was calculated to be 27. CONCLUSIONS: Assembly of
      thermostable enzymes enables the flexible design and construction of an in vitro
      metabolic pathway specialized for chemical manufacture. We herein report the in
      vitro construction of a bypassed pathway capable of an almost stoichiometric
      conversion of pyruvate to acetyl-CoA. This pathway is potentially applicable not
      only to N-acetylglutamate production but also to the production of a wide range
      of acetyl-CoA-derived metabolites.

PMID- 24099462
TI  - To use or not to use: a stage-based approach to understanding condom use among
      homeless youth.
AB  - This study used a stage-based approach to understand condom use behavior in a
      representative sample of 309 sexually active homeless youth recruited from
      shelters, drop-in centers, and street sites in Los Angeles County. Focusing on
      the youth's most recent sexual event, the three stages of condom use examined
      were: (1) whether the partners decided prior to the event about using condoms;
      (2) whether a condom was available at the event; and (3) whether a condom was
      used at the event. Logistic regression analysis was used to identify attitudinal,
      relationship, and contextual correlates of each of these three stages. Deciding
      ahead of time about condom use was associated with being Hispanic, level of
      education, condom attitudes, and various relationship characteristics (e.g.,
      partner type, monogamy, relationship abuse), with the nature of these
      associations varying depending on the type of decision (i.e., deciding to use,
      deciding to not use). Condom availability was more likely to be reported by
      males, if the event was described as being special in some way, or if the event
      lacked privacy. Condom use was more likely among youth with more positive condom
      attitudes and among youth who decide ahead of time to use a condom, but less
      likely among those in monogamous relationships or when hard drugs were used prior
      to sex. Whether sexual intercourse is protected or unprotected is the end result
      of a series of decisions and actions by sexual partners. Results from this study
      illustrate how condom use can be better understood by unpacking the stages and
      identifying influential factors at each stage. Each stage may, in and of itself,
      be an important target for intervention with homeless youth. 

PMID- 24099463
TI  - Spontaneous vegetation encroachment upon bauxite residue (red mud) as an
      indicator and facilitator of in situ remediation processes.
AB  - The spontaneous colonization of a bauxite residue (alumina refining tailings)
      deposit by local vegetation in Linden, Guyana, over 30 years, indicates that
      natural weathering processes can ameliorate tailings to the extent that it can
      support vegetation. Samples were collected from vegetated and unvegetated areas
      to investigate the relationships between bauxite residue properties and
      vegetation cover. Compared to unvegetated areas, bauxite residue in vegetated
      areas had lower pH (mean pH 7.9 vs 10.9), lower alkalinity (mean titratable
      alkalinity 0.4 vs 1.4 mol H(+) kg(-1)), lower electrical conductivity (mean EC
      0.3 vs 2.1 mS cm(-1)), lower total Al (mean Al2O3 19.8 vs 25.8% wt) and Na (mean
      Na2O 0.9 vs 3.7% wt), and less sodalite and calcite. Accumulation of N, NH4(+),
      and organic C occurred under vegetation, demonstrating the capacity for plants to
      modify residue to suit their requirements as a soil-like growth medium. Aeolian
      redistribution of coarse grained tailings appeared to support vegetation
      establishment by providing a thin zone of enhanced drainage at the surface.
      Natural pedogenic processes may be supplemented by irrigation, enhanced drainage,
      and incorporation of sand and organic matter at other tailings deposits to
      accelerate the remediation process and achieve similar results in a shorter time
      frame. 

PMID- 24099464
TI  - Delivery room breastfeeding for prevention of hypoglycaemia in infants of
      diabetic mothers.
AB  - OBJECTIVE: To evaluate the effect of duration of early breastfeeding in the
      delivery room on blood glucose levels among term neonates of diabetic mothers.
      METHODS: Mothers with gestational diabetes were encouraged to breastfeed their
      infants immediately after birth in the delivery room. The breastfeeding duration
      was recorded by the midwife. RESULTS: The longer duration of breastfeeding
      subgroup (n = 39) demonstrated a lower rate of hypoglycaemia in the first 8 hours
      of life (< 40 mg/dl) compared to the shorter duration subgroup (n = 40), but this
      difference did not reach statistical significance (2.6% vs. 17.5% respectively, p
      = 0.057). Hypoglycaemia was mainly predicted by lower cord glucose for each
      decrease of 10 mg/dl (OR 2.11 [CI 1.1-4.03] p = 0.024. CONCLUSION: Longer
      duration of delivery room breastfeeding did not reduce the rate of hypoglycaemia,
      which was mainly influenced by lower cord blood glucose level.

PMID- 24099465
TI  - Synthesis and functionalisation of magnetic nanoparticles for hyperthermia
      applications.
AB  - A summary of recent developments in the synthesis, stabilisation and coating of
      magnetic iron oxide nanoparticles for hyperthermia applications is presented.
      Methods for synthesis in aqueous, organic and microemulsion systems are reviewed
      together with the resulting heating rates of the nanoparticles. Different
      stabilisation mechanisms for iron oxide nanoparticles from aqueous and organic
      media are discussed as intermediates for further coating and functionalisation.
      Coating with silica and/or polysaccharides is mainly used for design of
      nanoparticles especially for targeted hyperthermia application. These coatings
      permit versatile functionalisation as a basis for conjugating biomolecules, e.g.
      antibodies or peptides. Various strategies to conjugate biomolecules on the
      particle surface are discussed, with emphasis on methods that preserve
      biofunctionality after immobilisation. The efficiency of established methods such
      as carbodiimide coupling and oriented conjugation strategies is compared with new
      developments such as the bioorthogonal approaches that are based on the
      cycloaddition of strain-promoted alkynes with azides or nitrones. For targeted
      hyperthermia applications the study of the formation of a protein corona around
      nanoparticles with site-specific biomolecules on the surface is essential to
      achieve improved circulation times in the blood and reduced non-specific uptake
      by non-targeted organs for a high specific accumulation in the target tissue.

PMID- 24099466
TI  - Meta-analysis: rectal indomethacin for the prevention of post-ERCP pancreatitis.
AB  - BACKGROUND: Despite initial evidence in the literature, nonsteroidal anti
      inflammatory drugs (NSAIDs) have not been widely used to prevent post-endoscopic
      retrograde cholangiopancreatography (ERCP) pancreatitis (PEP). AIM: To complete a
      meta-analysis of high-quality RCTs that included the latest available literature
      published after past meta-analytical efforts METHODS: A comprehensive electronic
      literature search was carried out for RCTs comparing peri-procedural rectal
      indomethacin and placebo in preventing PEP. Methodological quality was assessed
      by the Cochrane risk of bias tool. Fixed model Mantel-Haenszel meta-analysis, Q
      test and I(2) index were used. Several subgroup and sensitivity analyses were
      planned. RESULTS: A total of four of 61 retrieved trials between 2007 and 2012 (n
      = 1470) were included. No significant publication bias existed. All studies used
      similar criteria to detect pancreatitis. The pooled proportion estimate of the
      rate of pancreatitis was 5.1% with indomethacin and 10.3% with placebo. After
      excluding the high-risk patients, the rates were 3.9% and 7.9% respectively.
      Fixed model meta-analysis showed that the rate of pancreatitis was significantly
      lower using indomethacin as compared with placebo [OR = 0.49(0.34-0.71); P =
      0.0002]. Number needed to treat was 20. There was no significant statistical or
      clinical heterogeneity. In subgroup analysis, the difference remained unchanged
      for average-risk population [OR = 0.49(0.28-0.85); P = 0.01] or in preventing
      severe PEP [OR = 0.41(0.21-0.78); P = 0.007]. The result of the main outcome
      remained robust in multiple sensitivity analyses. CONCLUSIONS: Rectal
      indomethacin used immediately before or after ERCP significantly reduces the risk
      of PEP to half in both low- and high-risk patients, and with both statistically
      and clinically significant conclusions. These results suggest that a possible
      change in routine practice for patients at both low and high risk of developing
      PEP should be advocated.

PMID- 24099467
TI  - Review article: dermatological complications of immunosuppressive and anti-TNF
      therapy in inflammatory bowel disease.
AB  - BACKGROUND: With the expanding list of medications available to treat patients
      with inflammatory bowel disease (IBD), it is important to recognise adverse
      events, including those involving the skin. Dermatological adverse events may be
      confused with extra-intestinal manifestations of IBD. AIM: To review drug-related
      dermatological manifestations associated with immunosuppressive and anti-tumour
      necrosis factor (anti-TNF) therapy. METHODS: The literature was searched on
      PubMed for dermatological adverse events in IBD. RESULTS: Present thiopurine
      exposure was associated with a 5.9-fold [95% confidence interval (CI), 2.1-16.4]
      increased risk of developing non-melanoma skin cancer (NMSC). The peak incidence
      is highest in Caucasians over the age of 65 years with crude incidence rates of
      4.0 and 5.7/1000 patient-years for present and previous use. In anti-TNF-exposed
      subjects, drug-induced lupus was reported in 1% of the cases and a psoriatic rash
      in up to 3% of the cases. Anti-TNF monotherapy increases the risk of NMSC ~2-fold
      to a rate of 0.5 cases per 1000 person-years. Cutaneous lymphomas have been
      rarely reported in subjects on thiopurine or anti-TNF drug monotherapy.
      Combination therapy seems to have an additive effect on the risk of developing
      NMSC and lymphoma. CONCLUSIONS: Physicians need to be aware of the wide spectrum
      of dermatological complications of immunosuppressive and anti-TNF therapy in IBD,
      especially psoriasis and non-melanoma skin cancer. Vigilance and regular
      screening for non-melanoma skin cancer is recommended. Case discussions between
      gastroenterologists and dermatologists should be undertaken to best manage
      dermatological adverse events.

PMID- 24099468
TI  - Review article: the association between nodular regenerative hyperplasia,
      inflammatory bowel disease and thiopurine therapy.
AB  - BACKGROUND: Nodular regenerative hyperplasia (NRH) is increasingly being
      recognised in patients with inflammatory bowel disease (IBD). However, the
      pathogenesis and incidence of NRH in IBD, and the putative roles played by
      azathioprine (AZA), mercaptopurine (MP), or tioguanine (TG) remain unclear. AIMS:
      To summarise the data on the association between NRH and thiopurine therapy in
      patients with IBD. METHODS: A literature search was performed in PubMed and
      MEDLINE databases using the keywords 'nodular regenerative hyperplasia AND
      (inflammatory bowel disease OR Crohn's disease OR ulcerative colitis) AND
      (azathioprine OR mercaptopurine OR tioguanine OR thioguanine).' No time limit was
      placed on studies included. RESULTS: Inflammatory bowel disease patients treated
      with AZA have a cumulative incidence of NRH of approximately 0.6% and 1.28% at 5
      and 10 years, respectively, whereas those treated with high-dose TG (>40 mg/day)
      have a frequency of NRH of up to 62%, which is higher in patients with elevated
      liver enzymes and/or thrombocytopaenia than those without these abnormalities
      (frequency 76% vs. 33%). Conversely, low-dose TG therapy (<20 mg/day) is
      relatively safe, with no cases of NRH observed. NRH has also been found in 6% of
      operated thiopurine-naive IBD patients. Male gender, older age, and stricturing
      disease/small bowel resection have been consistently identified as high-risk
      factors for NRH. CONCLUSIONS: The pathogenesis of nodular regenerative
      hyperplasia in patients with IBD is complex and multifactorial involving disease
      specific, genetic and iatrogenic risk factors. Clinicians should maintain a high
      index of suspicion for diagnosing nodular regenerative hyperplasia, especially in
      IBD patients with high-risk factors on thiopurine therapy, regardless of the
      presence of laboratory abnormalities.

PMID- 24099469
TI  - Telaprevir-based triple therapy for chronic hepatitis C patients with advanced
      fibrosis: a prospective clinical study.
AB  - BACKGROUND: Antiviral treatment is recommended for chronic hepatitis C patients
      with advanced fibrosis to reduce and prevent cirrhosis-related complications.
      AIM: To evaluate the efficacy and safety of telaprevir (TVR)-based triple therapy
      for patients with advanced fibrosis in a clinical practice setting. METHODS: This
      prospective, multicentre study consisted of 102 patients with advanced fibrosis
      (METAVIR score F3-4) who were infected with HCV genotype 1b. All received 12
      weeks of TVR in combination with 24 weeks of pegylated interferon (PEG-IFN)
      alpha2b and ribavirin (RBV). RESULTS: The sustained virological response (SVR)
      rate was 69.6% (71 of 102). Notably, for treatment-naive and prior relapse
      patients the SVR rate was over 80%. Previous treatment response, interleukin 28B
      polymorphism (rs8099917) and rapid virological response (undetectable HCV RNA at
      week 4) were independently associated with SVR. To achieve SVR, an adequate
      dosage of PEG-IFNalpha2b (>=1.2 MUg/kg/week) and RBV (>=7.5 mg/kg/day) is
      preferable; however, the mean weight-adjusted TVR dosage had little impact on
      treatment outcome. Although severe blood cytopaenia and a dermatological disorder
      were frequently found, the rate of discontinuation due to adverse effects was
      12.7%. The inosine triphosphatase CC allele (rs1127354) was independently
      associated with the development of severe anaemia, and lower serum albumin level
      (<35 g/L) was associated with the occurrence of infection. CONCLUSIONS: The great
      gain in the SVR rate by telaprevir-based triple therapy offsets the problems with
      adverse effects; thus, it should be considered as a potent treatment protocol for
      patients with advanced fibrosis, especially for those with treatment-naive and
      prior relapse.

PMID- 24099470
TI  - Novel serological neo-epitope markers of extracellular matrix proteins for the
      detection of portal hypertension.
AB  - BACKGROUND: The hepatic venous pressure gradient (HVPG) is an invasive, but
      important diagnostic and prognostic marker in cirrhosis with portal hypertension
      (PHT). During cirrhosis, remodelling of fibrotic tissue by matrix
      metalloproteinases (MMPs) is a permanent process generating small fragments of
      degraded extracellular matrix (ECM) proteins known as neoepitopes, which are then
      released into the circulation. AIM: To investigate their potential as plasma
      markers for detection of PHT. METHODS: Ninety-four patients with alcoholic
      cirrhosis and 20 liver-healthy controls were included. Clinical and laboratory
      data of the patients were collected. All patients received HVPG measurement with
      blood sampling. In these samples, the following degradation or formation markers
      were measured: C1M (type I-collagen), C3M and PRO-C3 (type III collagen), C4M and
      P4NP 7S (type IV collagen), C5M (type V collagen), C6M (type VI collagen), BGM
      (biglycan), ELM (elastin), CRPM (CRP). RESULTS: All ECM markers except for CRPM
      correlated significantly with HVPG. Interestingly, C4M, C5M and ELM levels were
      significantly higher in patients with HVPG >10 mmHg. Multiple regression analysis
      identified PRO-C3, C6M and ELM as significant determinants, while the models A
      and B including PRO-C3, ELM, C6M and model for end-stage liver disease (MELD)
      provided better description of PHT (r = 0.75, P < 0.0001). The models provided
      odds ratios of >100 for having clinical significant PHT. CONCLUSIONS: These novel
      non-invasive extracellular matrix markers reflect the degree of liver
      dysfunction. The different degrees of portal hypertension correlated with these
      circulating neoepitopes. Using a single blood sample, these neoepitopes in
      combination with MELD detect the level of portal hypertension.

PMID- 24099471
TI  - Factors associated with thiopurine non-adherence in patients with inflammatory
      bowel disease.
AB  - BACKGROUND: Medication non-adherence seems to be a particular problem in younger
      patients with inflammatory bowel disease (IBD) and has a negative impact on
      disease outcome. AIMS: To assess whether non-adherence, defined using thiopurine
      metabolite levels, is more common in young adults attending a transition clinic
      than adults with IBD and whether psychological co-morbidity is a contributing
      factor. We also determined the usefulness of the Modified Morisky 8-item
      Adherence Scale (MMAS-8) to detect non-adherence. METHODS: Seventy young adults
      [51% (36) male] and 74 [62% (46) male] adults were included. Psychological co
      morbidity was assessed using the Hospital Anxiety Depression Scale (HADS) and
      self-reported adherence using the MMAS-8. RESULTS: Twelve percent (18/144) of the
      patients were non-adherent. Multivariate analysis [OR, (95% CI), P value]
      confirmed that being young adult [6.1 (1.7-22.5), 0.001], of lower socio-economic
      status [1.1 (1.0-1.1), <0.01] and reporting higher HADS-D scores [1.2 (1.0-1.4),
      0.01] were associated with non-adherence. Receiver operator curve analysis of
      MMAS-8 scores gave an area under the curve (95% CI) of 0.85 (0.77-0.92), (P <
      0.0001): using a cut-off of <6, the MMAS-8 score has a sensitivity of 94% and a
      specificity of 64% to predict thiopurine non-adherence. Non-adherence was
      associated with escalation in therapy, hospital admission and surgeries in the
      subsequent 6 months of follow up. CONCLUSIONS: Non-adherence to thiopurines is
      more common in young adults with inflammatory bowel disease, and is associated
      with lower socio-economic status and depression. The high negative predictive
      value of MMAS-8 scores <6 suggests that it could be a useful screen for
      thiopurine non-adherence.

PMID- 24099472
TI  - The management of iron deficiency in inflammatory bowel disease--an online tool
      developed by the RAND/UCLA appropriateness method.
AB  - BACKGROUND: Iron deficiency is a common and undertreated problem in inflammatory
      bowel disease (IBD). AIM: To develop an online tool to support treatment choice
      at the patient-specific level. METHODS: Using the RAND/UCLA Appropriateness
      Method (RUAM), a European expert panel assessed the appropriateness of treatment
      regimens for a variety of clinical scenarios in patients with non-anaemic iron
      deficiency (NAID) and iron deficiency anaemia (IDA). Treatment options included
      adjustment of IBD medication only, oral iron supplementation, high-/low-dose
      intravenous (IV) regimens, IV iron plus erythropoietin-stimulating agent (ESA),
      and blood transfusion. The panel process consisted of two individual rating
      rounds (1148 treatment indications; 9-point scale) and three plenary discussion
      meetings. RESULTS: The panel reached agreement on 71% of treatment indications.
      'No treatment' was never considered appropriate, and repeat treatment after
      previous failure was generally discouraged. For 98% of scenarios, at least one
      treatment was appropriate. Adjustment of IBD medication was deemed appropriate in
      all patients with active disease. Use of oral iron was mainly considered an
      option in NAID and mildly anaemic patients without disease activity. IV regimens
      were often judged appropriate, with high-dose IV iron being the preferred option
      in 77% of IDA scenarios. Blood transfusion and IV+ESA were indicated in
      exceptional cases only. CONCLUSIONS: The RUAM revealed high agreement amongst
      experts on the management of iron deficiency in patients with IBD. High-dose IV
      iron was more often considered appropriate than other options. To facilitate
      dissemination of the recommendations, panel outcomes were embedded in an online
      tool, accessible via http://ferroscope.com/.

PMID- 24099473
TI  - Risk factors of gastrointestinal bleeding in clopidogrel users: a nationwide
      population-based study.
AB  - BACKGROUND: The risk factors for gastrointestinal bleeding (GIB) in clopidogrel
      users have not been identified. AIM: To clarify whether clopidogrel use is a risk
      factor for upper GIB (UGIB) and lower GIB (LGIB) and identify the risk factors in
      clopidogrel users. METHODS: Using the National Health Insurance Research Database
      of Taiwan, 3238 clopidogrel users and 12,952 age-, sex-, and enrolment time
      matched controls in a 1:4 ratio were extracted for comparison from a cohort
      dataset of 1,000,000 randomly sampled subjects. Cox proportional hazard
      regression models were used to identify the independent risk factors for UGIB and
      LGIB in all enrollees and clopidogrel users after adjustments for age, gender,
      comorbidity [i.e., coronary artery disease, hypertension, diabetes, chronic
      obstructive pulmonary disease, chronic kidney disease (CKD), cirrhosis,
      uncomplicated peptic ulcer disease, and peptic ulcer bleeding (PUB)], and
      medications [e.g., nonsteroidal anti-inflammatory drugs (NSAIDs), cyclooxygenase
      2 inhibitors, aspirin, steroids, selective serotonin reuptake inhibitors (SSRIs),
      warfarin and alendronate]. RESULTS: Cox proportional hazard regression analysis
      showed that use of clopidogrel increased the risk of UGIB [hazard ratio (HR):
      3.66; 95% confidence interval (CI): 2.96-4.51] and LGIB [HR: 3.52, 95% CI: 2.74
      4.52]. Age, CKD, PUB history, use of aspirin and NSAIDs were independent risk
      factors for UGIB in the clopidogrel users. Age, CKD, PUB history, use of aspirin
      and SSRIs were independent risk factors for LGIB. CONCLUSIONS: In clopidogrel
      users, age, CKD, PUB history, use of aspirin and NSAIDs are independent risk
      factors for UGIB; age, CKD, PUB history, use of aspirin and SSRIs are independent
      risk factors for LGIB.

PMID- 24099474
TI  - Twice-daily dosing of esomeprazole effectively inhibits acid secretion in CYP2C19
      rapid metabolisers compared with twice-daily omeprazole, rabeprazole or
      lansoprazole.
AB  - BACKGROUND: Twice-daily dosing of proton pump inhibitors (PPIs) is used to treat
      Helicobacter pylori or acid-related diseases, such as gastro-oesophageal reflux
      disease (GERD) refractory to standard dose of a PPI. Genetic polymorphisms of
      CYP2C19 are involved to different extents in the metabolism of four kinds of PPIs
      (omeprazole, lansoprazole, rabeprazole and esomeprazole) available in Japan. AIM:
      To compare acid-inhibitory effects of the four PPIs dosed twice daily in relation
      to CYP2C19 genotype. METHODS: We performed 24-h pH monitoring studies on Day 7 of
      PPI treatment for 40 Japanese H. pylori-negative volunteers [15 CYP2C19 rapid
      metabolisers (RMs), 15 intermediate metabolisers (IMs) and 10 poor metabolisers
      (PMs)] using a randomised four-way crossover design: omeprazole 20 mg,
      esomeprazole 20 mg, lansoprazole 30 mg and rabeprazole 10 mg twice daily.
      RESULTS: Although median pH values with esomeprazole, omeprazole, lansoprazole
      and rabeprazole were 5.7 (3.5-7.2), 5.5 (2.4-7.2), 5.5 (3.7-7.3) and 5.2 (2.5
      7.3), respectively (no statistically significant differences), CYP2C19 genotype
      dependent differences were smaller for esomeprazole and rabeprazole compared with
      values for omeprazole and lansoprazole. In CYP2C19 RMs, the median pH with
      esomeprazole [5.4 (3.5-6.8)] was significantly higher than those with omeprazole
      [5.0 (2.4-5.9), P = 0.018], lansoprazole [4.7 (3.7-5.5), P = 0.017] or
      rabeprazole [4.8 (2.5-6.4), P = 0.002]. In IMs and PMs, the median pH was >5.0
      independent of the PPI. CONCLUSIONS: In intermediate and rapid metabolisers of
      CYP2C19, PPIs dosed twice daily could attain sufficient acid suppression, while
      in CYP2C19 RMs, esomeprazole 20 mg twice daily caused the strongest inhibition of
      the four PPIs. Therefore, esomeprazole may be effective in Japanese population
      when dosed twice daily.

PMID- 24099475
TI  - Commentary: 5-ASA switches in IBD, adherence and flares.

PMID- 24099476
TI  - Commentary: biopsy to diagnose GERD--better, but not yet a stand-alone test.

PMID- 24099477
TI  - Commentary: 5-ASA switches in IBD, adherence and flares--authors' reply.

PMID- 24099478
TI  - Commentary: biopsy to diagnose GERD--better, but not yet a stand-alone test;
      authors' reply.

PMID- 24099479
TI  - Commentary: synbiotics and gut microbiota in older people--a microbial guide to
      healthy ageing.

PMID- 24099480
TI  - Letter: treatment of autoimmune acute liver failure--beyond consensus guidelines.

PMID- 24099481
TI  - Letter: treatment of autoimmune acute liver failure--beyond consensus guidelines;
      author's reply.

PMID- 24099483
TI  - Strain-responsive structural colored elastomers by fixing colloidal crystal
      assembly.
AB  - Colloidal crystal assembly film was prepared by using monodispersed colloidal
      particles of cross-linked random copolymer of methyl methacrylate and ethyl
      acrylate prepared by soap-free emulsion polymerization. The colloidal crystal
      film exhibited structural color when swollen with ethyl acrylate monomer. The
      structural color was maintained even after polymerization of the swelling monomer
      and cross-linker, suggesting the colloidal crystalline order was successfully
      fixed and embedded in the matrix of poly(ethyl acrylate) elastomer. Stretching
      deformation of the structural colored elastomer induced a sensitive change to
      shorter wavelength color. Peak wavelength of the UV-vis absorption spectrum of
      the stretched elastomer revealed an excellent proportional relationship with film
      thickness. In the swollen colloidal crystal film, ethyl acrylate was absorbed in
      the colloidal particle; therefore, poly(ethyl acrylate) chain should be
      penetrating into the colloidal particle after the polymerization of the matrix
      elastomer. This interpenetrated polymer network structure was considered to be
      effective for the rubber-like elasticity and sensitive strain-responsive color
      changing phenomena of the structural colored elastomer. 

PMID- 24099482
TI  - Overtraining is associated with DNA damage in blood and skeletal muscle cells of
      Swiss mice.
AB  - BACKGROUND: The alkaline version of the single-cell gel (comet) assay is a useful
      method for quantifying DNA damage. Although some studies on chronic and acute
      effects of exercise on DNA damage measured by the comet assay have been
      performed, it is unknown if an aerobic training protocol with intensity, volume,
      and load clearly defined will improve performance without leading to peripheral
      blood cell DNA damage. In addition, the effects of overtraining on DNA damage are
      unknown. Therefore, this study aimed to examine the effects of aerobic training
      and overtraining on DNA damage in peripheral blood and skeletal muscle cells in
      Swiss mice. To examine possible changes in these parameters with oxidative
      stress, we measured reduced glutathione (GSH) levels in total blood, and GSH
      levels and lipid peroxidation in muscle samples. RESULTS: Performance evaluations
      (i.e., incremental load and exhaustive tests) showed significant intra and inter
      group differences. The overtrained (OTR) group showed a significant increase in
      the percentage of DNA in the tail compared with the control (C) and trained (TR)
      groups. GSH levels were significantly lower in the OTR group than in the C and TR
      groups. The OTR group had significantly higher lipid peroxidation levels compared
      with the C and TR groups. CONCLUSIONS: Aerobic and anaerobic performance
      parameters can be improved in training at maximal lactate steady state during 8
      weeks without leading to DNA damage in peripheral blood and skeletal muscle cells
      or to oxidative stress in skeletal muscle cells. However, overtraining induced by
      downhill running training sessions is associated with DNA damage in peripheral
      blood and skeletal muscle cells, and with oxidative stress in skeletal muscle
      cells and total blood.

PMID- 24099484
TI  - Navigating the cultural transition alone: psychosocial adjustment of Korean early
      study abroad students.
AB  - Precollege study abroad in English-speaking countries is an increasingly popular
      educational strategy among Asian families. We used grounded theory method to
      construct a model of cultural adjustment process for unaccompanied minors based
      the retrospective narratives of 10 (8 male) South Korean adolescents who came to
      the United States, unaccompanied by parents, to attend middle schools or high
      schools. We found that unaccompanied minors' cultural adjustment progressed from
      their predeparture ambivalence to initial sense of vulnerability to an eventual
      sense of reengagement. Unaccompanied minor students' pervasive sense of
      vulnerability upon arrival was heightened not only by their lack of English
      fluency but also their reluctance to seek the support of parents in Korea and of
      local Korean peers. This study has implications for educators and counselors in
      secondary schools who work with international students who are unaccompanied
      minors.

PMID- 24099485
TI  - Perceived context of reception among recent Hispanic immigrants:
      conceptualization, instrument development, and preliminary validation.
AB  - Context of reception has been discussed widely in the sociological and
      anthropological literature, but no measures of this construct exist. We designed
      a measure of perceived context of reception and provide initial support for the
      factorial validity, internal consistency reliability, and incremental and
      discriminant validity of scores generated by this measure. A sample of 302 recent
      immigrant Hispanic parent-adolescent dyads from Miami and Los Angeles completed
      the new perceived context of reception measure, as well as measures of perceived
      discrimination; Hispanic/American cultural practices, values, and
      identifications; and depressive symptoms. In Phase 1, exploratory and
      confirmatory factor analyses extracted a factor for negative perceived context of
      reception. A subscale corresponding to this factor was used in Phase 2; for
      parents and adolescents, negative perceived context of reception and perceived
      discrimination were differentially associated with acculturation-related
      variables-suggesting discriminant validity between perceived discrimination and
      negative perceived context of reception. For adolescents at both sites and for
      parents in Los Angeles only, the negative perceived context of reception
      dimensions were significantly associated with depressive symptoms 6 months later,
      over and above the contribution made by perceived discrimination--suggesting
      incremental validity. Results are discussed in terms of perceived context of
      reception as a new and emerging construct.

PMID- 24099486
TI  - Depression among Black bisexual men with early and later life adversities.
AB  - This study examined the role of adulthood adversities in the relationship between
      childhood adversities and depression in 117 HIV-positive Black men who have sex
      with men and women (MSMW) and who have histories of childhood sexual abuse (CSA).
      Men were participants in the Enhanced Sexual Health Intervention for Men, a 6
      session health intervention, and, at baseline, reported their experiences of CSA,
      childhood adversities, perceived discrimination, chronic stress, social support,
      and depressive symptoms. The relationship between childhood adversities,
      including CSA, and depression was mediated by experiences with racial and HIV
      discrimination, R2 = .25, F(3, 112) = 12.67, p < .001, and chronic stress, R2 =
      .17, F(3, 112) = 7.41, p < .001. Social support moderated the mediated effects of
      both racial and HIV discrimination, b = -.154, t(111) = -2.82, p < .01, and
      chronic stress, b = -.019, t(111) = -3.759, p < .01. Men's early adverse
      experiences were predictive of depression in adulthood; however, this
      relationship was largely affected by adulthood experiences, specifically
      discrimination, high chronic stress, and low social support. These findings
      illustrate pathways by which Black MSMW's early vulnerability for depression is
      either exacerbated or attenuated by their experiences as adults.

PMID- 24099488
TI  - Dysphagia in Lewy body dementia - a clinical observational study of swallowing
      function by videofluoroscopic examination.
AB  - BACKGROUND: Dysphagia, which can result in aspiration pneumonia and death, is a
      well-known problem in patients with dementia and Parkinson's disease. There are
      few studies on dysphagia in patients with dementia with Lewy bodies (DLB) and
      Parkinson's disease dementia (PDD), especially studies objectively documenting
      the type of swallowing dysfunction. The aim of this study was therefore to
      investigate the prevalence, and define the actual swallowing dysfunction
      according to a videofluoroscopic swallowing examination (VFSE) in patients with
      DLB and PDD. METHODS: Eighty-two consecutive patients with DLB or PDD in a
      clinical follow-up program were asked about symptoms of dysphagia. Those
      experiencing dysphagia were examined with VFSE. Prevalence and type of swallowing
      dysfunction was recorded. RESULTS: Twenty-six patients (32%) reported symptoms of
      dysphagia such as swallowing difficulties or coughing. Twenty-four (92%) of these
      had a documented swallowing dysfunction on VFSE. Eighty-eight percent suffered
      from pharyngeal dysfunction. CONCLUSIONS: Almost all DLB or PDD patients with
      subjective signs of dysphagia had pathologic results on VFSE, the majority of
      pharyngeal type. This type of dysphagia has not been reported in DLB before. The
      results have clinical implications and highlight the importance of asking for and
      examining swallowing function to prevent complications such as aspiration.

PMID- 24099489
TI  - Verbal and visual stimulation effects on rectus femoris and biceps femoris
      muscles during isometric and concentric.
AB  - BACKGROUND: Coactivation may be both desirable (injury prevention) or undesirable
      (strength measurement). In this context, different styles of muscle strength
      stimulus have being investigated. In this study we evaluated the effects of
      verbal and visual stimulation on rectus femoris and biceps femoris muscles
      contraction during isometric and concentric. METHODS: We investigated 13 men (age
      =23.1 +/- 3.8 years old; body mass =75.6 +/- 9.1 kg; height =1.8 +/- 0.07 m). We
      used the isokinetic dynamometer BIODEX device and an electromyographic (EMG)
      system. We evaluated the maximum isometric and isokinetic knee extension and
      flexion at 60 degrees /s. The following conditions were evaluated: without visual
      nor verbal command (control); verbal command; visual command and; verbal and
      visual command. In relation to the concentric contraction, the volunteers
      performed five reciprocal and continuous contractions at 60 degrees /s. With
      respect to isometric contractions it was made three contractions of five seconds
      for flexion and extension in a period of one minute. RESULTS: We found that the
      peak torque during isometric flexion was higher in the subjects in the VVC
      condition (p > 0.05). In relation to muscle coactivation, the subjects presented
      higher values at the control condition (p > 0.05). CONCLUSION: We suggest that
      this type of stimulus is effective for the lower limbs.

PMID- 24099487
TI  - Membrane remodeling by alpha-synuclein and effects on amyloid formation.
AB  - alpha-Synuclein (alpha-Syn), an intrinsically disordered protein, is associated
      with Parkinson's disease. Though molecular pathogenic mechanisms are ill-defined,
      mounting evidence connects its amyloid forming and membrane binding propensities
      to disease etiology. Contrary to recent data suggesting that membrane remodeling
      by alpha-syn involves anionic phospholipids and helical structure, we discovered
      that the protein deforms vesicles with no net surface charge
      (phosphatidylcholine, PC) into tubules (average diameter ~20 nm). No discernible
      secondary structural changes were detected by circular dichroism spectroscopy
      upon the addition of vesicles. Notably, membrane remodeling inhibits alpha-syn
      amyloid formation affecting both lag and growth phases. Using five single
      tryptophan variants and time-resolved fluorescence anisotropy measurements, we
      determined that alpha-syn influences bilayer structure with surprisingly weak
      interaction and no site specificity (partition constant, Kp ~ 300 M(-1)). Vesicle
      deformation by alpha-syn under a variety of different lipid/protein conditions is
      characterized via transmission electron microscopy. As cellular membranes are
      enriched in PC lipids, these results support possible biological consequences for
      alpha-syn induced membrane remodeling related to both function and pathogenesis. 

PMID- 24099490
TI  - Two-step reset in the resistance switching of the Al/TiOx/Cu structure.
AB  - Two-step reset behaviors in the resistance switching properties of the top
      Al/TiOx/bottom Cu structure were studied. During the electroforming and set
      steps, two types of conducting filaments composed of Cu and oxygen vacancies (Cu
      CF and V(O)-CF) were simultaneously (or sequentially) formed when Al was
      negatively biased. In the subsequent reset step with the opposite bias polarity,
      the Cu-CFs ruptured first at ~0.5 V, and formed an intermediate state. The trap
      filled V(O)-CFs were transformed into a trap-empty state, resulting in a high
      resistance state at ~1 V. Matrix phase in the electrochemical metallization cell
      can play an active role in resistance switching.

PMID- 24099492
TI  - The meaning of 'native'.

PMID- 24099491
TI  - Evaluation of age-dependent susceptibility in calves infected with two doses of
      Mycobacterium avium subspecies paratuberculosis using pathology and tissue
      culture.
AB  - The longstanding assumption that calves of more than 6 months of age are more
      resistant to Mycobacterium avium subspecies paratuberculosis (MAP) infection has
      recently been challenged. In order to elucidate this, a challenge experiment was
      performed to evaluate age- and dose-dependent susceptibility to MAP infection in
      dairy calves. Fifty-six calves from MAP-negative dams were randomly allocated to
      10 MAP challenge groups (5 animals per group) and a negative control group (6
      calves). Calves were inoculated orally on 2 consecutive days at 5 ages: 2 weeks
      and 3, 6, 9 or 12 months. Within each age group 5 calves received either a high -
      or low - dose of 5 * 109 CFU or 5 * 107 CFU, respectively. All calves were
      euthanized at 17 months of age. Macroscopic and histological lesions were
      assessed and bacterial culture was done on numerous tissue samples. Within all 5
      age groups, calves were successfully infected with either dose of MAP. Calves
      inoculated at < 6 months usually had more culture-positive tissue locations and
      higher histological lesion scores. Furthermore, those infected with a high dose
      had more severe scores for histologic and macroscopic lesions as well as more
      culture-positive tissue locations compared to calves infected with a low dose. In
      conclusion, calves to 1 year of age were susceptible to MAP infection and a high
      infection dose produced more severe lesions than a low dose.

PMID- 24099494
TI  - Impact of diagnosis threat on academic self-efficacy in mild traumatic brain
      injury.
AB  - The current study examined the effect of diagnosis threat on self-efficacy and
      neuropsychological performance in mild traumatic brain injury (TBI). Forty-nine
      participants with a history of mild TBI were randomized to a diagnosis threat or
      control group. The diagnosis threat group were told they were selected based on
      their history of TBI, while control group participants were told to perform their
      best. Individuals in the diagnosis threat group reported significantly lower
      academic self-efficacy than control participants. The groups performed
      differently on only one neuropsychological measure. These results suggest that
      diagnosis threat may have a greater impact on psychological factors than on
      cognitive performance. 

PMID- 24099493
TI  - Sleepless nights in the ICU: the awaken family.
AB  - Having a loved-one in the ICU is a traumatic experience for family members that
      can lead to a cluster of psychological complications, recently defined as post
      intensive care family syndrome. In a previous issue of Critical Care, Day and
      colleagues stressed the severe sleep disturbance and fatigue experienced by a
      majority of ICU patient family members. However, despite this burden being well
      characterised, the best preventive coping strategy remains undetermined. 

PMID- 24099495
TI  - Changing of the guard.

PMID- 24099496
TI  - Neuroimaging and electrophysiology in predicting treatment responsiveness in
      depression: bridging the lab-to-clinic divide?

PMID- 24099497
TI  - Neuroimaging-based biomarkers in psychiatry: clinical opportunities of a paradigm
      shift.
AB  - Neuroimaging research has substantiated the functional and structural
      abnormalities underlying psychiatric disorders but has, thus far, failed to have
      a significant impact on clinical practice. Recently, neuroimaging-based diagnoses
      and clinical predictions derived from machine learning analysis have shown
      significant potential for clinical translation. This review introduces the key
      concepts of this approach, including how the multivariate integration of patterns
      of brain abnormalities is a crucial component. We survey recent findings that
      have potential application for diagnosis, in particular early and differential
      diagnoses in Alzheimer disease and schizophrenia, and the prediction of clinical
      response to treatment in depression. We discuss the specific clinical
      opportunities and the challenges for developing biomarkers for psychiatry in the
      absence of a diagnostic gold standard. We propose that longitudinal outcomes,
      such as early diagnosis and prediction of treatment response, offer definite
      opportunities for progress. We propose that efforts should be directed toward
      clinically challenging predictions in which neuroimaging may have added value,
      compared with the existing standard assessment. We conclude that diagnostic and
      prognostic biomarkers will be developed through the joint application of expert
      psychiatric knowledge in addition to advanced methods of analysis. 

PMID- 24099498
TI  - Electrocortical features of depression and their clinical utility in assessing
      antidepressant treatment outcome.
AB  - Major depressive disorder (MDD) is primarily characterized by decreased affect
      and accompanying behavioural consequences, but it is also associated with
      cognitive dysfunction. Assessment of electroencephalographic (EEG) activity and
      associated event-related potentials (ERPs; derived from averaged EEG activity in
      response to a stimulus) in the context of MDD has provided insights into the
      electrocortical abnormalities associated with the disorder. Importantly, EEG and
      ERPs also have emerged as candidates for predicting and optimizing antidepressant
      (AD) treatment outcome. This is critical in light of relatively low remission
      rates or a limited response to initial AD interventions. In contrast to other
      neuroimaging approaches, EEG and ERPs may be superior for predicting and
      monitoring AD response, as electrocortical measures are relatively inexpensive,
      easy to use, and have excellent temporal (that is, millisecond) resolution,
      enabling fine-grained assessment of basic cognitive and emotive processes. This
      review aims to highlight the most consistently noted EEG and ERP features in MDD,
      which may one day assist with diagnostic confirmation, as well as the potential
      clinical utility of specific electrocortical measures in aiding with response
      prediction. 

PMID- 24099499
TI  - Processes of in-hospital psychiatric care and subsequent criminal behaviour among
      patients with schizophrenia: a national population-based, follow-up study.
AB  - OBJECTIVES: It is unknown whether evidence-based, in-hospital processes of care
      may influence the risk of criminal behaviour among patients with schizophrenia.
      Our study aimed to examine the association between guideline recommended in
      hospital psychiatric care and criminal behaviour among patients with
      schizophrenia. METHODS: Danish patients with schizophrenia (18 years or older)
      discharged from a psychiatric ward between January 2004 and March 2009 were
      identified using a national population-based schizophrenia registry (n = 10 757).
      Data for in-hospital care and patient characteristics were linked with data on
      criminal charges obtained from the Danish Crime Registry until November 2010.
      RESULTS: Twenty per cent (n = 2175) of patients were charged with a crime during
      follow-up (median = 428 days). Violent crimes accounted for 59% (n = 1282) of the
      criminal offences. The lowest risk of crime was found among patients receiving
      the most processes of in-hospital care (top quartile of received recommended
      care, compared with bottom quartiles, adjusted hazard ratio = 0.86, 95% CI 0.75
      to 0.99). The individual processes of care associated with the lowest risk of
      criminal behaviour were antipsychotic treatment and staff contact with relatives.
      CONCLUSIONS: High-quality, in-hospital psychiatric care was associated with a
      lower risk of criminal behaviour after discharge among patients with
      schizophrenia.

PMID- 24099500
TI  - Changes in treated incidence of borderline personality disorder in denmark: 1970
      2009.
AB  - OBJECTIVES: To investigate whether there are any trends in treated incidence of
      borderline personality disorder (BPD) in Danish psychiatric hospitals based on
      different diagnostic systems from 1970 to 2009. METHODS: All patients diagnosed
      with BPD for the first time as a main or an auxiliary diagnosis treated in in- or
      outpatient facilities in Danish psychiatric hospitals were identified through the
      Danish Psychiatric Central Research Register. Age-standardized, sex-specific, and
      standardized rates were calculated for the International Classification of
      Diseases (ICD), Eighth Revision, diagnostic period from 1970 to 1993 and the ICD
      10 diagnostic period from 1994 to 2009. RESULTS: The incidence for BPD in females
      as a main or an auxiliary diagnosis increased linearly from 1970 to 2009 (beta =
      0.69 per 100 000 per year [95% CI 0.66 to 0.73]). The rates for males also
      increased linearly from 1970 to 1993 (beta = 0.37 [95% CI 0.30 to 0.43]) followed
      by a linearly decrease (beta = -0.22 [95% CI -0.29 to -0.15]) in the ICD-10
      period from 1994 to 2009. The increase in females with BPD after the mid-1990s is
      smaller when controlling for outpatients mandatorily registered from 1995.
      CONCLUSION: The lack of defined criteria for BPD in ICD-8 may have been
      interpreted broadly to mean Kernberg's overarching concept of borderline
      personality organization, resulting in similar rates for males and females.
      However, in ICD-10, clinicians using the more narrow criteria for emotionally
      unstable personality disorder (borderline type), tended to diagnose BPD more
      commonly in women. These results suggest the importance of using specific
      criteria in diagnosing. They also suggest the importance of stability in the
      diagnostic criteria for BPD and other disorders.

PMID- 24099501
TI  - The burden of mental illness and addiction in ontario.
AB  - OBJECTIVE: Public Health Ontario and the Institute for Clinical Evaluative
      Sciences have collaborated to estimate the burden of illness attributable to
      mental disorder and addictions in Ontario. METHODS: Health-adjusted life years
      were used to estimate burden. It is conceptually similar to disability-adjusted
      life years that were used in the global burden of disease studies. Data sources
      for the mental illnesses and addictions used in our study included health
      administrative data for the province of Ontario, survey data from Statistics
      Canada and the Centre for Addiction and Mental Health, vital statistics data from
      the Ontario Office of the Registrar General, and US epidemiologic survey data.
      RESULTS: The 5 conditions with the highest burden are: major depression, bipolar
      affective disorder, alcohol use disorders (AUDs), social phobia, and
      schizophrenia. The burden of depression is double the next highest mental health
      condition (that is, bipolar affective disorder) and is more than the combined
      burden of the 4 most common cancers in Ontario. AUDs were the only disease group
      that had a substantial proportion of burden attributable to early death. The
      burden estimates for the other conditions were primarily due to disability.
      CONCLUSIONS: The burden of these conditions in Ontario is as large or larger than
      other conditions, such as cancer and infectious diseases, owing in large part to
      the high prevalence, chronicity, and age of onset for most mental disorders and
      addiction problems. The findings serve as an important baseline for future
      evaluation of interventions intended to address the burden of mental health and
      addictions.

PMID- 24099502
TI  - [SURPS French version validation in a Quebec adolescent population].
AB  - OBJECTIVE: The Substance Use Risk Profile Scale (SURPS) has been developed to
      screen personality risk factors for substance abuse. This scale assesses 4 high
      risk personality traits using a 23-item, self-report questionnaire. SURPS helps
      guiding targeted approaches to prevention of substance abuse and misuse. It has
      been validated in the United Kingdom, English Canada, Sri Lanka, and China. This
      study aims to validate this scale in a sample of French-speaking adolescents from
      Quebec as well as its sensitivity in a clinical sample of adolescents. METHOD:
      Two hundred two 15-year-old youths from a community sample completed a French
      version of SURPS as well as other measures of personality and substance use. This
      study reports the internal consistency and concurrent validity of the scale, as
      well as a factor analysis of items. Further, 40 youths (mean age 15.7 years) from
      a clinical population completed SURPS and their scores were compared with those
      of the community sample. RESULTS: SURPS French translation has good internal
      consistency and demonstrated a 4-factor structure very similar to the original
      scale. The 4 subscales show good concurrent validity, and 3 of the subscales were
      found to correlate with measures of substance use. Finally, 95% of the clinical
      sample was identified at high risk for substance misuse according to SURPS cut
      off scores. CONCLUSION: SURPS French translation seems to be a valid and
      sensitive scale that can be used in a French-speaking adolescent population from
      Quebec.

PMID- 24099503
TI  - Profiles of patients admitted to a psychiatric intensive care unit: secluded with
      or without restraint.
AB  - OBJECTIVE: To identify and describe the profiles of patients admitted to a
      psychiatric intensive care unit (PICU) as they relate to seclusion and restraint.
      METHOD: Multiple correspondence analysis (MCA) and cluster analysis were
      performed with data for 114 patients admitted to a PICU from June 8, 2010, to
      June 7, 2011. RESULTS: The MCA revealed that the presence or absence of seclusion
      and restraint was the main factor explaining the variance. Admitted patients fall
      into 5 profiles, 2 of which are significantly associated with seclusion and
      restraint: young psychotic men and women with bipolar disorder. CONCLUSIONS: The
      differentiation of patient profiles as they relate to seclusion and restraint
      should lead to the development of profile-specific interventions before, during,
      and after seclusion and restraint.

PMID- 24099504
TI  - Measurements of the fracture energy of lithiated silicon electrodes of Li-ion
      batteries.
AB  - We have measured the fracture energy of lithiated silicon thin-film electrodes as
      a function of lithium concentration. To this end, we have constructed an
      electrochemical cell capable of testing multiple thin-film electrodes in
      parallel. The stress in the electrodes is measured during electrochemical cycling
      by the substrate curvature technique. The electrodes are disconnected one by one
      after delithiating to various states of charge, that is, to various
      concentrations of lithium. The electrodes are then examined by optical microscopy
      to determine when cracks first form. All of the observed cracks appear brittle in
      nature. By determining the condition for crack initiation, the fracture energy is
      calculated using an analysis from fracture mechanics. In the same set of
      experiments, the fracture energy at a second state of charge (at small
      concentrations of lithium) is measured by determining the maximum value of the
      stress during delithiation. The fracture energy was determined to be Gamma = 8.5
      +/- 4.3 J/m(2) at small concentrations of lithium (~Li0.7Si) and have bounds of
      Gamma = 5.4 +/- 2.2 J/m(2) to Gamma = 6.9 +/- 1.9 J/m(2) at larger concentrations
      of lithium (~Li2.8Si). These values indicate that the fracture energy of
      lithiated silicon is similar to that of pure silicon and is essentially
      independent of the concentration of lithium. Thus, lithiated silicon demonstrates
      a unique ability to flow plastically and fracture in a brittle manner.

PMID- 24099505
TI  - Antigenotoxicity of Roupala montana extract in the mouse micronucleus and comet
      assays.
AB  - Roupala montana Aubl. (Proteaceae) is a typical savannah species and native to
      tropical South America that has a moderate mortality for adult forms of
      Schistossoma mansoni. Because this species has been little studied, the aim of
      this investigation was to evaluate the influence of R. montana extract on DNA
      damage induced by methyl methanesulfonate (MMS) in peripheral blood cells and
      liver of Swiss mice using the micronucleus and comet assay, respectively. R.
      montana dichloromethane extract was prepared from a stock solution (0.5 mg/mL) in
      5% dimethyl sulfoxide in water. Animals received a single dose of different
      concentrations of R. montana (5, 10 and 20 mg/kg body weight) by gavage (0.5
      mL/animal). For antigenotoxicity assessment, different concentrations of R.
      montana were administered simultaneously with MMS diluted in water (40 mg/kg,
      intraperitoneally; 0.3 mL/animal). Peripheral blood and hepatocyte samples were
      obtained 48 and 24 h after treatment, respectively. Results showed that R.
      montana administered alone indicated the absence of genotoxicity in the mouse
      micronucleus or comet assay. On the other hand, administration of different doses
      of R. montana concomitantly with MMS led to a significant reduction in frequency
      of micronucleated polychromatic erythrocytes and DNA damage, when compared to the
      group treated only with MMS. Further, for the micronucleus assay, the gradual
      increase of R. montana concentration led to a proportional increase in the
      reduction of genotoxicity induced by MMS, indicating a dose-response
      relationship.

PMID- 24099506
TI  - The effects of pharmacological treatment on functional brain connectome in
      obsessive-compulsive disorder.
AB  - BACKGROUND: Previous neuroimaging studies of obsessive-compulsive disorder (OCD)
      have reported both baseline functional alterations and pharmacological changes in
      localized brain regions and connections; however, the effects of selective
      serotonin reuptake inhibitor (SSRI) treatment on the whole-brain functional
      network have not yet been elucidated. METHODS: Twenty-five drug-free OCD patients
      underwent resting-state functional magnetic resonance imaging. After 16-weeks,
      seventeen patients who received SSRI treatment were rescanned. Twenty-three
      matched healthy control subjects were examined at baseline for comparison, and 21
      of them were rescanned after 16 weeks. Topological properties of brain networks
      (including small-world, efficiency, modularity, and connectivity degree) were
      analyzed cross-sectionally and longitudinally with graph-theory approach.
      RESULTS: At baseline, OCD patients relative to healthy control subjects showed
      decreased small-world efficiency (including local clustering coefficient, local
      efficiency, and small-worldness) and functional association between default-mode
      and frontoparietal modules as well as widespread altered connectivity degrees in
      many brain areas. We observed clinical improvement in OCD patients after 16 weeks
      of SSRI treatment, which was accompanied by significantly elevated small-world
      efficiency, modular organization, and connectivity degree. Improvement of
      obsessive-compulsive symptoms was significantly correlated with changes in
      connectivity degree in right ventral frontal cortex in OCD patients after
      treatment. CONCLUSIONS: This is first study to use graph-theory approach for
      investigating valuable biomarkers for the effects of SSRI on neuronal circuitries
      of OCD patients. Our findings suggest that OCD phenomenology might be the outcome
      of disrupted optimal balance in the brain networks and that reinstating this
      balance after SSRI treatment accompanies significant symptom improvement.

PMID- 24099507
TI  - A three-component model of relational responding in the transposition paradigm.
AB  - We present a new model of transposition behavior that involves 3 predictors: (a)
      the disparity in generalized associative strength from the previously reinforced
      and nonreinforced stimuli (g) to the stimuli in the testing pair; (b) relational
      disparity (r), the difference in the logarithmically scaled sensory values of the
      testing stimuli; and (c) familiarity (f), the inverse of the Euclidean distance
      from the testing pair to the nearest training pair in 2-dimensional stimulus
      space. We evaluated the model with pigeons as subjects and with circle diameter
      (Experiment 1) and speed of motion (Experiment 2) as sensory dimensions. In each
      experiment, we presented 1, 2, or 3 training pairs as well as a wide range of
      testing pairs, including those comprising nonadjacent training stimuli. The
      control that was exerted by g did not depend on the number of training pairs and
      predicted behavior better than r and f after 1-pair training. In contrast, the
      influence of r increased dramatically with an increase in the number of training
      pairs. The contribution of f depended on the stimulus domain: When circle area
      was used (Experiment 1), the influence of f was similar to r; however, when speed
      of motion was used (Experiment 2), f had no discernible effect on pigeons'
      behavior. In sum, our results suggest that pigeons' transposition behavior is
      affected by both reinforcement history (g) and the relation between the
      experimental stimuli (r and f); our model provides a principled means for
      assessing the relative contribution of each predictor to choice behavior.

PMID- 24099508
TI  - Relative salience versus relative validity: cue salience influences blocking in
      human associative learning.
AB  - Two studies of human contingency learning investigated the influence of stimulus
      salience on the cue competition effect of blocking. These studies demonstrated
      that blocking (defined as a difference in responding to blocked and control cues)
      was greater for target cues that had high "semantic salience" than those of lower
      salience. Moreover participants showed weaker responding to high salience blocked
      cues than low salience blocked cues, but a corresponding difference was not
      observed for control cues. These findings suggest that the influence of relative
      salience on associative learning depends on the relative validity of the cues in
      question. Use of eye tracking in Experiment 2 demonstrated that participants'
      overt attention to cues was also influenced by both relative salience and
      relative validity. We describe three associative learning models, based on the
      attentional theory proposed by Mackintosh (1975), that are able to account for
      our key findings.

PMID- 24099509
TI  - Antifungal dimeric chalcone derivative kamalachalcone E from Mallotus
      philippinensis.
AB  - From the red coloured extract (Kamala) prepared through acetone extraction of the
      fresh whole uncrushed fruits of Mallotus philippinensis, one new dimeric chalcone
      (1) along with three known compounds 1-(5,7-dihydroxy-2,2,6-trimethyl-2H-1
      benzopyran-8-yl)-3-phenyl-2-propen-1-one (2), rottlerin (3) and 4'
      hydroxyrottlerin (4) were isolated. The structure of compound 1 was elucidated by
      1D and 2D NMR analyses that included HSQC, HMBC, COSY and ROESY experiments along
      with the literature comparison. Compounds 1-4 were evaluated for antifungal
      activity against different human pathogenic yeasts and filamentous fungi. The
      antiproliferative activity of the compounds was evaluated against Thp-1 cell
      lines. Compounds 1 and 2 both exhibited IC50 of 8, 4 and 16 MUg/mL against
      Cryptococcus neoformans PRL518, C. neoformans ATCC32045 and Aspergillus
      fumigatus, respectively. Compound 4, at 100 MUg/mL, showed 54% growth inhibition
      of Thp-1 cell lines. 

PMID- 24099510
TI  - Perspectives of middle-aged African-American women in the Deep South on
      antiretroviral therapy adherence.
AB  - Despite evidence of stabilization in some areas of the USA, HIV infection in
      black women is not declining in the Deep South. Using a phenomenological approach
      to qualitative inquiry, we investigated women's experiences influencing their
      adherence to highly active antiretroviral therapy (HAART) in an urban setting.
      Inclusion criteria specified black women who had been aware of their HIV status
      for at least two years and were engaged in HIV outpatient care. Twelve single
      face-to-face confidential in-depth semi-structured interviews were conducted from
      a sample of predominantly middle-aged women retained in care at an HIV clinic in
      Atlanta, Georgia. Data were analyzed by two independent reviewers and three
      themes emerged from the group of women's accounts of their experiences. First,
      sentinel events led to changes in perspective and motivated women to adhere to
      HAART. Second, recognition that one had the personal strength necessary to cope
      with HIV fostered adherence. Finally, relationships with healthcare providers
      especially trust issues surrounding this relationship, impacted adherence both
      positively and negatively. These findings suggest that HAART adherence is a
      complex issue among middle-aged urban black women with HIV in the Deep South.
      Providers caring for this patient population should recognize that sentinel
      events, personal strength, and positive healthcare relationships are
      opportunities to improve adherence. 

PMID- 24099511
TI  - Trehalose is not a universal solution for solid lipid nanoparticles freeze
      drying.
AB  - OBJECTIVE: To prepare stable and easy to handle formulation of solid lipid
      nanoparticles (SLNs) by freeze-drying with or without cryoprotectants, as
      appropriate. MATERIALS AND METHODS: SLNs were freeze-dried without
      cryoprotectants or with cryoprotectants in quantities selected by freeze-thaw
      test (sucrose, glucose) or literature search (trehalose, maltose). Appearance, re
      dispersability and size distribution of re-dispersed samples were evaluated.
      RESULTS: SLN could be freeze-dried using 10% sucrose, trehalose or maltose.
      Trehalose was effective in protecting one of presented formulations that was
      already very stable on its own; its efficiency in protecting other two
      formulations was limited. DISCUSSION: Our results are in line with various
      reports of successful freeze-drying of SLN, but considering the stability of
      original dispersions, no improvement was achieved. CONCLUSION: We confirmed that
      trehalose is among the most suitable cryoprotectant for SLN, however it did not
      improve shelf-life of the most stable formulation.

PMID- 24099513
TI  - Science for action-based nursing.

PMID- 24099514
TI  - Maternal-foetal attachment during early pregnancy in Taiwanese women pregnant by
      in vitro fertilization.
AB  - AIM: The aim of this study was to investigate maternal-foetal attachment at 9, 12
      and 20 weeks gestation and to identify factors that influenced maternal-foetal
      attachment in Taiwanese women who conceived by in vitro fertilization.
      BACKGROUND: Development of maternal-foetal attachment is an important part of
      taking on the maternal role. However, evidence about maternal-foetal attachment
      after assisted conception is inconclusive. DESIGN: A longitudinal design with
      repeated measures. METHODS: A prospective, longitudinal design with repeated
      measures was used. Over an 18-month period in 2006-2008, a convenience sample of
      160 women who conceived after undergoing successful in vitro fertilization were
      recruited from a major infertility care centre in Taiwan. Data were collected by
      self-reported measures, including: (1) Maternal-Foetal Attachment Scale; (2)
      Symptoms Checklist; (3) Pregnancy-related Anxiety Scale; (4) Social Support
      Apgar; (5) Chinese childbearing attitude Questionnaire; and (6) Awareness of
      Foetus Scale. The selected instruments to measure each variable were administered
      to participants at 9, 12 and 20 weeks gestation. RESULTS: Maternal-foetal
      attachment increased as pregnancy progressed from 9 to 20 weeks gestation.
      General linear mixed model showed predictors of maternal-foetal attachment
      included Chinese childbearing attitude, awareness of the foetus, and social
      support. CONCLUSION: Health provider awareness of cultural influences on the
      development of early maternal-foetal attachment of women pregnant by in vitro
      fertilization is needed. Prenatal education in early pregnancy might incorporate
      more information about foetal development to allow the mother to visualize her
      unborn child. Providing social support for women who were conceived by in vitro
      fertilization is beneficial to the development of maternal-foetal attachment.

PMID- 24099516
TI  - What gets highly cited in JAN? Can editors pick which articles will contribute to
      a journal's impact factor?

PMID- 24099517
TI  - Quantitative assessment of the formation of polychlorinated derivatives, PCDD/Fs,
      in the electrochemical oxidation of 2-chlorophenol as function of the electrolyte
      type.
AB  - The electrochemical degradation of 2-chlorophenol (2-CP) on boron-doped diamond
      (BDD) anodes was carried out using two electrolytes, NaCl and Na2SO4. Both
      electrolytes supported complete mineralization of 2-CP, but faster rates of
      degradation were observed in NaCl. After 4 h of oxidation, the total organic
      carbon (TOC) balance neared 100% with Na2SO4 for identifiable compounds, whereas
      4 mM of TOC remained unidentified with NaCl. Since chlorophenols are known to be
      precursors of polychlorinated dibenzo-p-dioxins and dibenzofurans (PCDD/Fs), a
      rigorous assessment of intermediate products was carried out. When near complete
      mineralization was achieved, the use of NaCl resulted in the concentration of
      total PCDD/Fs increasing 2.68 * 10(4) times compared to the untreated sample, and
      to toxicity values several times higher than the maximum level established by
      U.S. Environmental Protection Agency for water ingestion. When Na2SO4 was used,
      the increase in total PCDD/Fs concentration was 134 times lower than with NaCl
      and there was no significant 2,3,7,8-PCDD/Fs formation. Thus, we emphasize the
      importance of electrolyte selection in electro-oxidation processes, especially
      when PCDD/Fs precursors are initially present or may be formed in the treated
      water samples. 

PMID- 24099518
TI  - Design of a phase I clinical trial to evaluate intratumoral delivery of ErbB
      targeted chimeric antigen receptor T-cells in locally advanced or recurrent head
      and neck cancer.
AB  - Despite several advances, 5-year survival in patients with head and neck squamous
      cell carcinoma (HNSCC) remains unchanged at only 50%. The commonest cause of
      death is locally advanced/recurrent disease. Consequently, there is an unmet need
      for new approaches to improve local control in HNSCC. T4 immunotherapy is an
      autologous cell therapy in which peripheral blood T-cells are genetically
      engineered using a retroviral vector to coexpress two chimeric receptors: (i)
      T1E28z is a chimeric antigen receptor that engages multiple ErbB dimers that are
      commonly upregulated in HNSCC; (ii) 4alphabeta is a chimeric cytokine receptor
      that converts the weak mitogenic stimulus provided by interleukin (IL)-4 into a
      strong and selective growth signal, allowing preferential expansion and
      enrichment of T4(+) T-cells ex vivo. T4 immunotherapy exerts antitumor activity
      against HNSCC cell lines and tumors in vivo, without significant toxicity. Human
      T4(+) T-cells also engage mouse ErbB receptors, permitting safety testing in SCID
      Beige mice. Severe toxicity caused by cytokine release syndrome ensues when human
      T4(+) T-cells are administered at high doses to mice, particularly with advanced
      tumor burdens. However, such toxicity is not required for efficacy and is never
      seen if T-cells are administered by the intratumoral route. To exploit this, we
      have designed a first-in-man clinical trial in which T4(+) T-cells are
      administered to patients with locally advanced/recurrent HNSCC. Cells will be
      administered at a single sitting to multiple sites around the viable tumor
      circumference. A 3+3 dose escalation design will be used, starting at 10(7) cells
      (cohort 1), escalating to 10(9) cells (cohort 5). If maximum tolerated dose
      remains undefined, cohorts 6/7 will receive either low- or high-dose
      cyclophosphamide before 10(9) T4(+) T-cells. A panel of routine/in-house assays
      and imaging techniques will be used to monitor safety, efficacy, perturbation of
      endogenous antitumor immunity, immunogenicity, and T-cell trafficking.

PMID- 24099519
TI  - Recognition memory for novel syntactic structures.
AB  - It is commonly held that recognition memory for the surface syntax of language is
      not robust, especially when compared with memory for gist (e.g., Potter &
      Lombardi, 1998; Sachs, 1967). Nevertheless, it has been reported that memory for
      surface syntax occurs and can be surprisingly robust (e.g., Gurevich, Johnson, &
      Goldberg, 2011). However, most studies have focused on recognition memory for
      syntactic structures present in participants' native languages, but little is
      known about memory for novel (e.g., nonnative) syntactic structures. Adults were
      exposed under incidental learning conditions to a semiartificial language
      consisting of English words placed into non-English syntactic structures derived
      from Persian. They were then given an unexpected recognition memory test.
      Participants demonstrated clear recognition memory for novel syntactic
      structures. Overall, the results suggest that memory for surface syntax can be
      acquired under incidental learning conditions, consistent with previous findings
      in the implicit learning literature using nonlinguistic stimuli. The results also
      suggest that basic memory processes like those investigated in the recognition
      memory literature may be involved in the incidental learning of novel syntactic
      structures, consistent with some current neurocognitive approaches to language
      (e.g., Ullman, 2004).

PMID- 24099520
TI  - Successful combination chemotherapy with irinotecan hydrochloride and cisplatin
      for primary gastric small cell carcinoma: report of a case.
AB  - Primary gastric small cell carcinoma is a rare and aggressive malignant disease
      with a poor prognosis that was first reported in 1976 by Matsusaka et al. The
      incidence is very low and the clinicopathological features are similar to those
      of small cell lung carcinoma.We herein report a case of successful treatment by
      combination chemotherapy consisting of irinotecan hydrochloride and cisplatin for
      primary gastric small cell carcinoma. The patient was a 71-year-old male who was
      admitted to a local hospital with anemia. Gastrointestinal endoscopy revealed the
      presence of advanced gastric carcinoma at the upper region of the stomach. The
      patient underwent surgery, and the pathological diagnosis was small cell
      carcinoma due to the presence of the typical features of small round cells with
      scant cytoplasm that were positive for synaptophysin and chromogranin A in the
      resected specimen. The patient underwent subsequent combination chemotherapy,
      which provided him with over 1 year of survival and a good quality of life. We
      also present a review of the literature regarding chemotherapy for primary
      gastric small cell carcinoma. 

PMID- 24099522
TI  - Enhanced molecular transport in hierarchical silicalite-1.
AB  - Fundamental understanding of the mass transport of petrochemical and biomass
      derived molecules in microporous and mesoporous solid catalysts is important for
      developing the next generation of heterogeneous catalysts for traditional
      hydrocarbon processing including biomass pyrolysis and upgrading. Hierarchical
      zeolites with both micropores and mesopores exhibit enhanced mass transport and
      unique catalytic performance in reactions involving large molecules. However,
      quantitative description of mass transport in such materials remains elusive,
      owing to the complicated structure of hierarchical pores and difficulty in the
      synthesis of the materials with controllable structures. In this work, zero
      length column chromatography (ZLC) was used to study temperature-dependent
      diffusion of cyclohexane in silicalite-1, self-pillared pentasil (SPP) zeolite,
      and three-dimensionally ordered mesoporous imprinted (3DOm-i) silicalite-1. The
      samples were synthesized with controllable characteristic diffusion lengths from
      micrometer scale (ca. 20 MUm) to nanometer scale (ca. 2 nm), allowing systematic
      study of the effect of mesoporosity on the mass transport behavior of
      hierarchical zeolites. The results show that the introduction of mesoporosity can
      indeed significantly facilitate the mass transport of cyclohexane in hierarchical
      silicalite-1 by reducing diffusional time constants, indicating rapid overall
      adsorption and desorption. However, when the length scale of the material
      approaches several nanometers, the contribution from the surface resistance, or
      "surface barrier", to overall mass transfer becomes dominant. 

PMID- 24099521
TI  - Molecular differential diagnosis of follicular thyroid carcinoma and adenoma
      based on gene expression profiling by using formalin-fixed paraffin-embedded
      tissues.
AB  - BACKGROUND: Differential diagnosis between malignant follicular thyroid cancer
      (FTC) and benign follicular thyroid adenoma (FTA) is a great challenge for even
      an experienced pathologist and requires special effort. Molecular markers may
      potentially support a differential diagnosis between FTC and FTA in postoperative
      specimens. The purpose of this study was to derive molecular support for
      differential post-operative diagnosis, in the form of a simple multigene mRNA
      based classifier that would differentiate between FTC and FTA tissue samples.
      METHODS: A molecular classifier was created based on a combined analysis of two
      microarray datasets (using 66 thyroid samples). The performance of the classifier
      was assessed using an independent dataset comprising 71 formalin-fixed paraffin
      embedded (FFPE) samples (31 FTC and 40 FTA), which were analysed by quantitative
      real-time PCR (qPCR). In addition, three other microarray datasets (62 samples)
      were used to confirm the utility of the classifier. RESULTS: Five of 8 genes
      selected from training datasets (ELMO1, EMCN, ITIH5, KCNAB1, SLCO2A1) were
      amplified by qPCR in FFPE material from an independent sample set. Three other
      genes did not amplify in FFPE material, probably due to low abundance. All 5
      analysed genes were downregulated in FTC compared to FTA. The sensitivity and
      specificity of the 5-gene classifier tested on the FFPE dataset were 71% and 72%,
      respectively. CONCLUSIONS: The proposed approach could support histopathological
      examination: 5-gene classifier may aid in molecular discrimination between FTC
      and FTA in FFPE material.

PMID- 24099523
TI  - Two-photon chemistry from upper triplet states of thymine.
AB  - Photolysis of the benzophenone chromophore by means of high energy laser pulses
      has been used as a tool to populate upper thymine-like triplet states via
      intramolecular sensitization. These species undergo characteristic npi* triplet
      photoreactivity, as revealed by the Norrish-Yang photocyclization of 5-tert
      butyluracil. 

PMID- 24099524
TI  - Pilot study of locomotion improvement using hybrid assistive limb in chronic
      stroke patients.
AB  - BACKGROUND: Locomotor training using robots is increasingly being used for
      rehabilitation to reduce manpower and the heavy burden on therapists, and the
      effectiveness of such techniques has been investigated. The robot suit Hybrid
      Assistive Limb (HAL) has been developed to rehabilitate or support motor function
      in people with disabilities. The HAL provides motion support that is tailored to
      the wearer's voluntary drive. We performed a pilot clinical trial to investigate
      the feasibility of locomotor training using the HAL in chronic stroke patients,
      and to examine differences between two functional ambulation subgroups. METHODS:
      Sixteen stroke patients in the chronic stage participated in this study. All
      patients were trained with the HAL over 16 sessions (20-30 min/day within 2
      days/week). Primary outcomes were walking speed, cadence, and number of steps
      recorded during a 10-meter walk test (10MWT). Berg balance scale (BBS) and timed
      up and go (TUG) were also measured. All outcome measures were evaluated without
      wearing HAL assistance before and after the intervention in all patients as well
      as in the dependent ambulatory and independent ambulatory subgroups. RESULTS: All
      participants completed the intervention with no adverse events. Gait speed,
      cadence, number of steps during the 10MWT, and BBS increased significantly from
      0.41 m/s to 0.45 m/s (P = 0.031), from 68.6 steps/min to 72.0 steps/min (P =
      0.020), from 37.5 steps to 33.1 steps (P = 0.017), and from 40.6 to 45.4 (P =
      0.004) respectively. The TUG test score improved, although this difference was
      not statistically significant. The findings in the dependent ambulatory subgroup
      primarily contributed to the significant differences observed in the group as a
      whole. CONCLUSIONS: This pilot study showed that locomotor training using the HAL
      is feasible for chronic stroke patients. Randomized controlled trials are now
      required to demonstrate the effectiveness of HAL-based rehabilitation over
      conventional therapies. TRIAL REGISTRATION: UMIN000002969.

PMID- 24099525
TI  - Crystal structure of c5321: a protective antigen present in uropathogenic
      Escherichia coli strains displaying an SLR fold.
AB  - BACKGROUND: Increasing rates of antimicrobial resistance among uropathogens led,
      among other efforts, to the application of subtractive reverse vaccinology for
      the identification of antigens present in extraintestinal pathogenic E. coli
      (ExPEC) strains but absent or variable in non-pathogenic strains, in a quest for
      a broadly protective Escherichia coli vaccine. The protein coded by locus c5321
      from CFT073 E. coli was identified as one of nine potential vaccine candidates
      against ExPEC and was able to confer protection with an efficacy of 33% in a
      mouse model of sepsis. c5321 (known also as EsiB) lacks functional annotation and
      structurally belongs to the Sel1-like repeat (SLR) family. Herein, as part of the
      general characterization of this potential antigen, we have focused on its
      structural properties. RESULTS: We report the 1.74 A-resolution crystal structure
      of c5321 from CFT073 E. coli determined by Se-Met SAD phasing. The structure is
      composed of 11 SLR units in a topological organisation that highly resembles that
      found in HcpC from Helicobacter pylori, with the main difference residing in how
      the super-helical fold is stabilised. The stabilising effect of disulfide bridges
      in HcpC is replaced in c5321 by a strengthening of the inter-repeat hydrophobic
      core. A metal-ion binding site, uncharacteristic of SLR proteins, is detected
      between SLR units 3 and 4 in the region of the inter-repeat hydrophobic core.
      Crystal contacts are observed between the C-terminal tail of one molecule and the
      C-terminal amphipathic groove of a neighbouring one, resembling interactions
      between ligand and proteins containing tetratricopeptide-like repeats.
      CONCLUSIONS: The structure of antigen c5321 presents a mode of stabilization of
      the SLR fold different from that observed in close homologs of known structure.
      The location of the metal-ion binding site and the observed crystal contacts
      suggest a potential role in regulation of conformational flexibility and
      interaction with yet unidentified target proteins, respectively. These findings
      open new perspectives in both antigen design and for the identification of a
      functional role for this protective antigen.

PMID- 24099526
TI  - Surveillance of avian influenza virus type A in semi-scavenging ducks in
      Bangladesh.
AB  - BACKGROUND: Ducks are the natural reservoir of influenza A virus and the central
      host for highly pathogenic avian influenza (H5N1), while domestic ducks rearing
      in semi-scavenging system could serve as re-assortment vessels for re-emerging
      new subtypes of influenza viruses between birds to human. Avian influenza virus
      (AIV) surveillance in Bangladesh has been passive, relying on poultry farmers to
      report suspected outbreaks of highly pathogenic H5N1 influenza. Here, the results
      of an active surveillance effort focusing on the semi-scavenging ducks are
      presented. RESULT: A total of 2100 cloacal swabs and 2100 sera were collected
      from semi-scavenging ducks from three wintering-sites of Bangladesh during three
      successive winter seasons, December through February in the years between 2009
      and 2012. Virus isolation and identification were carried out from the cloacal
      swabs by virus propagation in embryonated hen eggs followed by amplification of
      viral RNA using Avian influenza virus (AIV) specific RT-PCR. The overall
      prevalence of avian influenza type A was 22.05% for swab samples and 39.76% ducks
      were sero-positive for avian influenza type A antibody. Extremely low sero
      prevalence (0.09%) of AIV H5N1 was detected. CONCLUSIONS: Based on our
      surveillance results, we conclude that semi-scavenging ducks in Bangladesh might
      play important role in transmitting Avian Influenza virus (AIV) type A. However,
      the current risk of infection for humans from domestic ducks in Bangladesh is
      negligible. We believe that this relatively large dataset over three winters in
      Bangladesh might create a strong foundation for future studies of AIV prevalence,
      evolution, and ecology in wintering sites around the globe.

PMID- 24099527
TI  - Guanylated polymethacrylates: a class of potent antimicrobial polymers with low
      hemolytic activity.
AB  - We have synthesized a series of copolymers containing both positively charged
      (amine, guanidine) and hydrophobic side chains (amphiphilic antimicrobial peptide
      mimics). To investigate the structure-activity relationships of these polymers,
      low polydispersity polymethacrylates of varying but uniform molecular weight and
      composition were synthesized, using a reversible addition-fragmentation chain
      transfer (RAFT) approach. In a facile second reaction, pendant amine groups were
      converted to guanidines, allowing for direct comparison of cation structure on
      activity and toxicity. The guanidine copolymers were much more active against
      Staphylococcus epidermidis and Candida albicans compared to the amine analogues.
      Activity against Staphylococcus epidermidis in the presence of fetal bovine serum
      was only maintained for guanidine copolymers. Selectivity for bacterial over
      mammalian cells was assessed using hemolytic and hemagglutination toxicity
      assays. Guanidine copolymers of low to moderate molecular weight and
      hydrophobicity had high antimicrobial activity with low toxicity. Optimum
      properties appear to be a balance between charge density, hydrophobic character,
      and polymer chain length. In conclusion, a suite of guanidine copolymers has been
      identified that represent a new class of antimicrobial polymers with high potency
      and low toxicity. 

PMID- 24099528
TI  - Polymeric infrared compatible microfluidic devices for spectrochemical analysis.
AB  - An innovative fabrication method is presented that affords the combination of
      polydimethyl-siloxane (PDMS) microfluidic technology with vibrational
      spectroscopy. PDMS devices are produced with uniform thicknesses ranging from 25
      to 400 MUm. The optical characteristics of the microfluidic devices in the mid
      infrared are reported. The broad utility of this approach is demonstrated through
      IR imaging of flows in functional gradient generators and flow-focusing devices. 

PMID- 24099529
TI  - Pathogenesis and prevention of placental and transplacental porcine reproductive
      and respiratory syndrome virus infection.
AB  - Porcine reproductive and respiratory syndrome virus (PRRSV)-induced reproductive
      problems are characterized by embryonic death, late-term abortions, early
      farrowing and increase in number of dead and mummified fetuses, and weak-born
      piglets. The virus recovery from fetal tissues illustrates transplacental
      infection, but despite many studies on the subject, the means by which PRRSV
      spreads from mother to fetus and the exact pathophysiological basis of the virus
      induced reproductive failure remain unexplained. Recent findings from our group
      indicate that the endometrium and placenta are involved in the PRRSV passage from
      mother to fetus and that virus replication in the endometrial/placental tissues
      can be the actual reason for fetal death. The main purpose of this review is to
      clarify the role that PRRSV replication and PRRSV-induced changes in the
      endometrium/placenta play in the pathogenesis of PRRSV-induced reproductive
      failure in pregnant sows. In addition, strategies to control placental and
      transplacental PRRSV infection are discussed. 

PMID- 24099530
TI  - The influence of pH and hypoxia on tumor metastasis.
AB  - Rapid malignant proliferation, prior to effective tumor neoangiogenesis, creates
      a microenvironment around solid cancers, which is predominantly hypoxic and
      characterized by a high interstitial fluid pressure. Presumably as an adaptive
      response, tumor cells favor metabolic activity with apparently inefficient energy
      output, and production of intermediates that promote cellular replication,
      preferentially through anaerobic glycolysis, a phenomenon that persists even in
      re-established normoxic conditions (anomalously referred to as 'aerobic
      glycolysis'). Extrusion of the consequently excessive accumulation of lactate and
      protons decreases extracellular pH, leading to a microenvironment considered
      conducive to promotion of tumor motility, invasion and metastasis, and one that
      will invariably influence response to drug treatment. This review will critically
      assess the evidence forming the basis of current understanding of the precise pH
      conditions in the extracellular tumor matrix, its regulation by cancer cells and
      relationship with hypoxia, its relevance to malignant progression and its
      exploitation for therapeutic advantage. 

PMID- 24099531
TI  - Effects of speech on proofreading: can task-engagement manipulations shield
      against distraction?
AB  - This article reports 2 experiments that examine techniques to shield against the
      potentially disruptive effects of task-irrelevant background speech on
      proofreading. The participants searched for errors in texts that were either
      normal (i.e., written in Times New Roman font) or altered (i.e., presented either
      in Haettenschweiler font or in Times New Roman but masked by visual noise) in 2
      sound conditions: a silent condition and a condition with background speech.
      Proofreading for semantic/contextual errors was impaired by speech, but only when
      the text was normal. This effect of speech was completely abolished when the text
      was written in an altered font (Experiment 1) or when it was masked by visual
      noise (Experiment 2). There was no functional difference between the 2 ways to
      alter the text with regard to the way the manipulations influenced the effects of
      background speech on proofreading. The results indicate that increased task
      demands, which lead to greater focal-task engagement, may shield against the
      distracting effects of background speech on proofreading.

PMID- 24099532
TI  - Priming thoughts about extravagance: implications for consumer decisions about
      luxury products.
AB  - If a semantic concept is accessible in memory, it can direct attention to the
      attributes of a target that exemplify this concept. When these attributes have
      both affective and utilitarian implications that are evaluatively opposite, the
      relative impact of these different implications depends on an individual's
      ability and motivation to expend the cognitive effort required to evaluate them.
      These assumptions were confirmed in six experiments on the impact of priming the
      concept of extravagance on attention to a product's luxury-related features and
      consequent reactions to it. Priming this concept decreased the choice of a luxury
      product if participants were both motivated and able to construe the utilitarian
      implications of the product's extravagance-related features. When participants
      were either distracted from deliberating on their choices or were asked to
      recommend a product to others, however, priming extravagance led them to base
      their judgments on the affective reactions that the features spontaneously
      elicited and consequently increased their choice of the product.

PMID- 24099534
TI  - 7th international conference on water in food.

PMID- 24099533
TI  - Severe burn and disuse in the rat independently adversely impact body composition
      and adipokines.
AB  - INTRODUCTION: Severe trauma is accompanied by a period of hypermetabolism and
      disuse. In this study, a rat model was used to determine the effects of burn and
      disuse independently and in combination on body composition, food intake and
      adipokines. METHODS: Male rats were assigned to four groups 1) sham ambulatory
      (SA), 2) sham hindlimb unloaded (SH), 3) 40% total body surface area full
      thickness scald burn ambulatory (BA) and 4) burn and hindlimb unloaded (BH).
      Animals designated to the SH and BH groups were placed in a tail traction system
      and their hindlimbs unloaded. Animals were followed for 14 days. Plasma, urine,
      fecal and tissue samples were analyzed. RESULTS: SA had a progressive increase in
      body mass (BM), SH and BA no change and BH a reduction. Compared to SA, BM was
      reduced by 10% in both SH and BA and by 17% when combined in BH. Compared to SA,
      all groups had reductions in lean and fat body mass with BH being greater. The
      decrease in lean mass was associated with the rate of urinary corticosterone
      excretion. The loss in fat mass was associated with decreases in plasma leptin
      and adiponectin and an increase in ghrelin. Following the acute response to
      injury, BH had a greater food intake per 100 g BM. Food intake was associated
      with the levels of leptin, adiponectin and ghrelin. CONCLUSIONS: The effects of
      the combination of burn and disuse in this animal model were additive, therefore
      in assessing metabolic changes with severe trauma both injury and disuse should
      be considered. Furthermore, the observed changes in adipokines, corticosterone
      and ghrelin provide insights for interventions to attenuate the hypermetabolic
      state following injury, possibly reducing catabolism and muscle loss and
      subsequent adverse effects on recovery and function.

PMID- 24099535
TI  - Molecular mobility, composition and structure analysis in glycerol plasticised
      chitosan films.
AB  - This study was developed with the purpose to investigate the effect of
      polysaccharide/plasticiser concentration on the microstructure and molecular
      dynamics of polymeric film systems, using transmission electron microscope
      imaging (TEM) and nuclear magnetic resonance (NMR) techniques. Experiments were
      carried out in chitosan/glycerol films prepared with solutions of different
      composition. The films obtained after drying and equilibration were characterised
      in terms of composition, thickness and water activity. Results show that glycerol
      quantities used in film forming solutions were responsible for films composition;
      while polymer/total plasticiser ratio in the solution determined the thickness
      (and thus structure) of the films. These results were confirmed by TEM. NMR
      allowed understanding the films molecular rearrangement. Two different behaviours
      for the two components analysed, water and glycerol were observed: the first is
      predominantly moving free in the matrix, while glycerol is mainly bounded to the
      chitosan chain. 

PMID- 24099536
TI  - Effect of relative humidity on carvacrol release and permeation properties of
      chitosan based films and coatings.
AB  - The influence of water vapour conditions on mass transport and barrier properties
      of chitosan based films and coatings were studied in relation to surface and
      structural properties. Water contact angles, material swelling, polymer
      degradation temperature, barrier properties (PO2, PCO2, WVP) and aroma diffusion
      coefficients were determined. The solvent nature and the presence of carvacrol
      influenced the surface and structural properties and then the barrier performance
      of activated chitosan films. Increasing RH from 0% to 100% led to a significant
      increase in material swelling. The plasticization effect of water was more
      pronounced at high humid environment, while at low RH the matrix plasticization
      was induced by carvacrol. The deposit of a thin chitosan layer on polyethylene
      decreased PO2 and PCO2 both in dry and humid conditions. The carvacrol release
      from the chitosan matrix was strongly influenced by RH. A temperature increase
      from 4 to 37 degrees C also had an impact on carvacrol diffusivity but to a
      lesser extent than RH.

PMID- 24099537
TI  - Effect of ultrasound treatment on the water state in kiwifruit during osmotic
      dehydration.
AB  - The present work investigates how ultrasound pretreatment modulates the effects
      of osmotic dehydration (OD) on the water state and microstructure of kiwifruit.
      Kiwifruit slices (10mm thick) were subjected to ultrasonic waves in a water bath
      at a frequency of 35 kHz for 10, 20 and 30 min. OD process was then carried out
      by immersing the samples in 61.5% sucrose solution equilibrated at 25 degrees C
      for a contact period of 0, 10, 20, 30, 60 and 120 min. The partition of water
      into the cellular tissue structures (vacuole, cytoplasm, extracellular spaces and
      cell wall) was investigated by Time Domain Nuclear Magnetic Resonance (TD-NMR).
      In parallel, the microstructure of kiwifruits slices was examined using a
      Scanning Electron Microscope. The results showed that US pretreatment performed
      for more than 10 min had a positive effect on the mass exchange caused by osmotic
      dehydration. A creation of microchannels and an increase of the average cross
      section area of cells were observed when the samples were pretreated with US
      before OD. TD-NMR showed a slight redistribution of water through the
      substructures of the cells, as a function of the length of the US pretreatment
      applied.

PMID- 24099538
TI  - Water-solid interactions between amorphous maltodextrins and crystalline sodium
      chloride.
AB  - The effects of co-formulating amorphous maltodextrins (MDs) and sodium chloride
      (NaCl), a deliquescent crystalline solid, on moisture sorption, deliquescence
      point (RH0), and glass transition temperature (Tg) behaviours were investigated.
      Moisture sorption profiles of binary NaCl:MD mixtures and individual ingredients
      were generated using controlled relative humidity (RH) desiccators at
      temperatures from 22 to 50 degrees C and by dynamic vapour sorption (DVS) and
      dynamic dewpoint sorption (DDS) techniques. Close proximity of MD and NaCl
      induced synergistic moisture uptake in binary mixtures above a threshold RH,
      resulting in significantly lower Tgs in binary mixtures compared to individual
      MDs. The RH0 of NaCl was also lower in the blends. Mixing amorphous MD with
      crystalline NaCl resulted in synergistic moisture sorption and reduced both Tg
      and RH0, thus blends were more sensitive to environmental moisture than the
      individual solids. This has implications for quality control of many formulated
      powder products.

PMID- 24099539
TI  - Multidisciplinary approach to study the effect of water status and mobility on
      the activity of peroxidase in solutions.
AB  - The effect of water mobility on horseradish peroxidase (HRP) activity in
      solutions was investigated by measuring water activity (aw), freezable water
      content, (1)H proton transverse relaxation time and water self-diffusivity
      determined by nuclear magnetic resonance. The effect of system mobility as
      described by viscosity and glass transition temperature (T'g) was also studied.
      The aw and viscosity of aqueous solutions were modulated using ligands (glucose,
      sorbitol and trehalose) and a thickener (maltodextrin). The effectiveness of a
      solute in the inhibition of HRP activity was better related to its ability to
      reduce the mobility of the system than to its water mobility depleting effect.
      The relationship among viscosity and peroxidase activity was influenced by the
      type of enzyme but not by the substrate. Bovine lactoperoxidase activity was
      hindered by viscosity changes more than HRP activity (tested in the same system)
      due to the higher molecular weight of the former enzyme.

PMID- 24099540
TI  - Structure formation in sugar containing pectin gels - influence of tartaric acid
      content (pH) and cooling rate on the gelation of high-methoxylated pectin.
AB  - The aim of the study was the application of a recently published method, using
      structuring parameters calculated from dG'/dt, for the characterisation of the
      pectin sugar acid gelation process. The influence of cooling rate and pH on
      structure formation of HM pectin gels containing 65 wt.% sucrose were
      investigated. The results show that the structure formation process as well as
      the properties of the final gels strongly depended on both parameters. With
      increasing cooling rates from 0.5 to 1.0 K/min the initial structuring
      temperature slightly decreased and the maximum structuring velocity increased.
      The lower the cooling rates, the firmer and more elastic were the final gels.
      With increasing acid content (decreasing pH from 2.5-2.0) the initial structuring
      temperatures were nearly constant. The final gel properties varied visibly but
      not systematically. Gels with the lowest and highest pH were less elastic and
      weaker compared to those with medium acid concentrations.

PMID- 24099541
TI  - Interfacial protein engineering for spray-dried emulsions - part I: effects on
      protein distribution and physical properties.
AB  - Distribution of protein and oil in aqueous and spray-dried emulsions and the
      effect of protein cross-linking on emulsion properties and matrix-water
      interactions were investigated. Sodium caseinate and sunflower oil were used to
      make emulsions which were spray dried using maltodextrin as a wall material. 3%
      Na-caseinate concentration showed optimum emulsion and process stability as
      observed in CLSM images, droplet size data and in the amount of heptane
      extractable oil from spray-dried emulsions. Transglutaminase cross-linking prior
      to emulsification slightly increased the amount of protein both on the oil
      droplet interface and on the particle surface as confirmed by analysis of
      continuous phase protein in the feed emulsion and by XPS measurements from the
      powder surface. DSC and water sorption measurements were used to study the
      physical state of the matrix. Glass transition occurred between RH 54% and 75% at
      room temperature and it was not affected by cross-linking.

PMID- 24099542
TI  - Interfacial protein engineering for spray-dried emulsions - part II: oxidative
      stability.
AB  - The aim of this work was to investigate how the oxidative stability of
      encapsulated oil is affected by the humidity response of a Na-caseinate
      maltodextrin matrix. Furthermore, the effect of modification of the interfacial
      Na-caseinate layer through cross-linking was studied. For this purpose, two model
      spray-dried emulsions containing sunflower oil, maltodextrin, and either non
      cross-linked or cross-linked Na-caseinate were stored at different relative
      humidities (RHs; ~0%, 11%, 33%, 54%, and 75%). Increasing RH improved the
      oxidative stability of the spray-dried emulsions. This behaviour was mainly
      linked to the loss of individual powder particles upon caking and collapsing of
      the matrix at RH 75%. Oxidation of non-encapsulated surface lipids with a
      proportion of ca. 5% of total lipids was only twofold compared to total lipids.
      Excess protein on particle surfaces may have delayed oxidation, e.g., by its
      radical scavenging activity. Under several storage conditions, cross-linking of
      the protein slightly improved the oxidative stability.

PMID- 24099543
TI  - Mechanical properties and microstructure of frozen carrots during storage as
      affected by blanching in water and sugar solutions.
AB  - Raw carrots and carrots blanched in water and in 4% trehalose and maltose
      solutions at 75 degrees C for 3 (A) and 10 min (C) and at 90 degrees C for 3 (B)
      and 10 min (D) were frozen and stored at -18 degrees C for eight months. The
      effects of heating conditions and exogenous added sugars on the mechanical
      properties and microstructure of the vegetable after blanching and during frozen
      storage were studied. By scanning electron microscopy (SEM) analysis no
      significant differences were observed among samples A and B water-blanched and
      raw carrot while a thermo-protective effect due to the sugars addition was
      evidenced in sample D, undergone to the most severe thermal treatment. Freezing
      and frozen storage determined several fractures on both raw and blanched carrots
      due to ice crystals formation and re-crystallisation. The cryo-protective effect
      of the sugars on the vegetable microstructure was observed only in the 'over
      blanched' sample D. The mechanical properties of carrots were affected by
      blanching which caused a hardness decrease but after freezing and one month of
      frozen storage, all samples showed a further dramatic reduction of hardness. Only
      samples characterised by a pectinesterase residual activity showed a softening
      also after one month of frozen storage likely for a competitive effect of the
      thermo-protective ability of trehalose on this enzyme. The exogenous trehalose
      was able to limit the hardness loss of carrots undergone to B, C and D blanching
      pre-treatments.

PMID- 24099544
TI  - Physico-chemical properties of ready to eat, shelf-stable pasta during storage.
AB  - The changes in physico-chemical properties of RTE shelf stable pasta were studied
      during storage with a multianalytical and multidimensional approach (with special
      focus on water status) to understand the ageing process in this product. Pasta
      hardness and amylopectin recrystallisation increased, macroscopic water status
      indicators and proton molecular translational mobility remained constant, and
      significant changes were measured in the proton rotational molecular mobility
      indicators ((1)H FID, (1)H T2) during storage. Since the main changes observed in
      RTE pasta during storage were similar to those observed in other cereal-based
      products, it would be interesting to verify the effect of the anti-staling
      methods commonly used in the cereal processing industry in improving RTE pasta
      shelf-stability.

PMID- 24099545
TI  - Monitoring methods and predictive models for water status in Jonathan apples.
AB  - Evaluation of water status in Jonathan apples was performed for 20 days. Loss
      moisture content (LMC) was carried out through slow drying of wholes apples and
      the moisture content (MC) was carried out through oven drying and lyophilisation
      for apple samples (chunks, crushed and juice). We approached a non-destructive
      method to evaluate LMC and MC of apples using image processing and multilayer
      neural networks (NN) predictor. We proposed a new simple algorithm that selects
      the texture descriptors based on initial set heuristically chosen. Both structure
      and weights of NN are optimised by a genetic algorithm with variable length
      genotype that led to a high precision of the predictive model (R(2)=0.9534). In
      our opinion, the developing of this non-destructive method for the assessment of
      LMC and MC (and of other chemical parameters) seems to be very promising in
      online inspection of food quality.

PMID- 24099546
TI  - Learning from number board games: you learn what you encode.
AB  - We tested the hypothesis that encoding the numerical-spatial relations in a
      number board game is a key process in promoting learning from playing such games.
      Experiment 1 used a microgenetic design to examine the effects on learning of the
      type of counting procedure that children use. As predicted, having kindergartners
      count-on from their current number on the board while playing a 0-100 number
      board game facilitated their encoding of the numerical-spatial relations on the
      game board and improved their number line estimates, numeral identification, and
      count-on skill. Playing the same game using the standard count-from-1 procedure
      led to considerably less learning. Experiment 2 demonstrated that comparable
      improvement in number line estimation does not occur with practice encoding the
      numerals 1-100 outside of the context of a number board game. The general
      importance of aligning learning activities and physical materials with desired
      mental representations is discussed.

PMID- 24099547
TI  - Contingency is not enough: Social context guides third-party attributions of
      intentional agency.
AB  - Four experiments investigated whether infants and adults infer that a novel
      entity that interacts in a contingent, communicative fashion with an experimenter
      is itself an intentional agent. The experiments contrasted the hypothesis that
      such an inference follows from amodal representations of the contingent
      interaction alone with the hypothesis that features of the experimenter's
      behavior might also influence intentional attribution. Twelve- to 13-month-old
      infants and adults observed a novel entity respond contingently to a confederate
      experimenter, the form of whose actions varied across conditions. For infants,
      intentionality attribution was assessed by the extent to which they subsequently
      followed the faceless entity's implied attentional focus. For adults,
      intentionality attribution was assessed from their use of psychological terms
      when later describing the entity's behavior. In both groups, construal of the
      entity as an intentional agent was limited to a subset of contingent interaction
      conditions. At both ages, the pattern of responses across conditions suggests
      that whether an observed contingent interaction can be seen as a social
      interaction influences the attribution of intentional agency. These results
      further indicate that the agent detection mechanism responding to third-party
      contingent interactions, as a context-sensitive process, is distinct from the
      mechanism responding to directly experienced contingent interactions, suggested
      by prior developmental work to be based solely on amodal representations of an
      entity's contingent reaction to behaviors of an infant.

PMID- 24099548
TI  - The first time ever I saw your feet: inversion effect in newborns' sensitivity to
      biological motion.
AB  - Inversion effect in biological motion perception has been recently attributed to
      an innate sensitivity of the visual system to the gravity-dependent dynamic of
      the motion. However, the specific cues that determine the inversion effect in
      naive subjects were never investigated. In the present study, we have assessed
      the contribution of the local gravity-dependent motion (i.e., the orientation of
      individual dot trajectories) and the global configuration (i.e., the vertical
      location of the dots representing the feet within the display) in determining the
      inversion effect for biological motion in humans at birth. Results showed that 2
      day-old newborns, at their 1st exposure to point-light displays, preferred a
      biological motion stimulus representing the legs of a walking animal compared
      with an identical display in which individual dot trajectories were locally
      inverted so that the motion violates the gravity force (Experiment 1).
      Interestingly, the global configuration affected the analysis of the gravity
      dependent profile of dots motion. Indeed, the spontaneous preference disappeared
      when the local dots representing feet were embedded in a more complex global
      display and all the dots representing feet were located on the ground below the
      rest of the body (Experiment 2). Finally, results revealed that the orientation
      of the global configuration per se is not a crucial factor in determining
      newborns' preference (Experiment 3). These results suggest that humans possess an
      inborn predisposition about the direction of the gravity force that imprints
      biological motion and supports the hypothesis that a mechanism for the detection
      of biological motion is already at work before visual experience.

PMID- 24099549
TI  - The hydrogen-peroxide-induced radical behaviour in human cytochrome c
      phospholipid complexes: implications for the enhanced pro-apoptotic activity of
      the G41S mutant.
AB  - We have investigated whether the pro-apoptotic properties of the G41S mutant of
      human cytochrome c can be explained by a higher than wild-type peroxidase
      activity triggered by phospholipid binding. A key complex in mitochondrial
      apoptosis involves cytochrome c and the phospholipid cardiolipin. In this complex
      cytochrome c has its native axial Met(80) ligand dissociated from the haem-iron,
      considerably augmenting the peroxidase capability of the haem group upon H2O2
      binding. By EPR spectroscopy we reveal that the magnitude of changes in the
      paramagnetic haem states, as well as the yield of protein-bound free radical, is
      dependent on the phospholipid used and is considerably greater in the G41S
      mutant. A high-resolution X-ray crystal structure of human cytochrome c was
      determined and, in combination with the radical EPR signal analysis, two tyrosine
      residues, Tyr(46) and Tyr(48), have been rationalized to be putative radical
      sites. Subsequent single and double tyrosine-to-phenylalanine mutations revealed
      that the EPR signal of the radical, found to be similar in all variants,
      including G41S and wild-type, originates not from a single tyrosine residue, but
      is instead a superimposition of multiple EPR signals from different radical
      sites. We propose a mechanism of multiple radical formations in the cytochrome c
      phospholipid complexes under H2O2 treatment, consistent with the stabilization of
      the radical in the G41S mutant, which elicits a greater peroxidase activity from
      cytochrome c and thus has implications in mitochondrial apoptosis.

PMID- 24099550
TI  - Influence of alkalizers on dissolution properties of telmisartan in solid
      dispersions prepared by cogrinding.
AB  - The amorphous solid dispersions of telmisartan salts were prepared by cogrinding,
      in presence of alkalizers and polyvinylpyrrolidone (PVPk30). Five alkalizers in
      this study were MgO, Na2CO3, K2CO3, NaHCO3 and meglumine. In soft mode using a
      roll mill, the drug could not form salt with MgO or NaHCO3, whereas partial drug
      had been transformed into salt with carbonates or meglumine. Under cogrinding,
      the organic base meglumine was easier to react with telmisartan than other two
      carbonates. For getting good dissolution performance, the drug had to be
      transformed into salt completely. A high intensity oscillating mill was applied
      for producing telmisartan meglumine salt. Multi-instrumental characterizations
      attested the formation of amorphous salt by high mechanical process, involving
      dissolution test, fourier transform infrared spectroscopy and powder X-ray
      diffractometry. It was evident that solid dispersions of telmisartan meglumine
      salt significantly increased the drug dissolution rate in intestinal fluid.

PMID- 24099551
TI  - Pharmaceutical and pharmacokinetic characterization of a novel sublingual
      buprenorphine/naloxone tablet formulation in healthy volunteers.
AB  - CONTEXT: Bitter taste, as well as dissolve time, presents a significant challenge
      for the acceptability of formulations for oral transmucosal drug delivery.
      OBJECTIVE: To characterize a novel sublingual tablet formulation of
      buprenorphine/naloxone with regards to pharmacokinetics, dissolve time and
      formulation acceptability. METHODS: Dry mixing techniques were employed to
      produce a small and fast dissolving buprenorphine/naloxone sublingual tablet
      formulation, OX219 (Zubsolv(r)), using sucralose and menthol as sweetener and
      flavor to mask the bitter taste of the active ingredients. Two cross-over studies
      were performed in healthy volunteers to evaluate pharmacokinetics, dissolve time
      and acceptability of OX219 5.7/1.4 mg tablets compared to the commercially
      available buprenorphine/naloxone formulations Suboxone(r) tablets and films (8/2
      mg). RESULTS: Buprenorphine exposure was equivalent in OX219 and Suboxone
      tablets. Sublingual dissolve times were significantly shorter for OX219 than for
      Suboxone tablets and were similar to Suboxone films. The OX219 formulation
      received significantly higher subjective ratings for taste and overall
      acceptability than both Suboxone formulations. OX219 was preferred over Suboxone
      tablet and film formulations by 77.4% and 88.9% of subjects, respectively.
      CONCLUSIONS: A sublingual tablet formulation with an improved acceptability has
      been successfully developed.

PMID- 24099552
TI  - To study physical compatibility between dibasic calcium phosphate and cohesive
      actives using powder rheometer and thermal methods.
AB  - AIM: An attempt is made to provide better understanding of the compatibility
      aspect of excipients with different properties of active pharmaceutical
      ingredient (API) using various rheological, thermal and morphological studies
      conducted on binary mixtures of Dibasic Calcium Phosphate anhydrous (DCP-A) and
      Dibasic Calcium Phosphate dihydrate (DCP-D) forms with cohesive API's
      (Acetaminophen and Aspirin). METHOD: Binary mixtures of DCP's were prepared by
      addition of 0% w/w to 50% w/w of the API in each powder blend. Powder rheological
      analysis were conducted using FT4 powder rheometer, rotational shear cell and
      empirical approaches such as angle of repose (AOR), Hausner ratio (HR) and Carr's
      index (CI). Thermal analysis was conducted using differential scanning
      calorimetry (DSC) and thermal effusivity. Morphological studies were conducted
      using Scanning Electron Microscopy (SEM) to determine the fundamental differences
      between powder materials. Result/Conclusions: Powder rheometer showed distinctive
      understanding in the flowability behavior of binary mixtures with addition of
      increasing proportion of API's than empirical approaches. Thermal approaches
      revealed the potential interaction of water of crystallization DCP-D while such
      interaction was absent in DCP-A. Binary mixtures prepared using DCP-D were better
      flowable while blends containing DCP-A were better in stability (physical),
      compressibility and permeability. This study allows the scientist to understand
      the powder packing of different blends with their flowability and compressibility
      parameter and helps selection of appropriate form of hydrate for relevant API.

PMID- 24099553
TI  - The impact of chirality on the development of robust and stable tablet
      formulation of (S-) amlodipine besylate.
AB  - The aim of this study was to compare the specific characteristics of the S
      enantiomer and the racemate of amlodipine besylate (AB) in order to design a
      robust and stable formulation of the active S-enantiomer which will guarantee
      continuous performance of the unichiral version of amlodipine. Preformulation
      studies showed that the S-enantiomer and the racemate exhibit different crystal
      morphology, particle size distribution and higroscopicity. The S-enantiomer
      exhibited significantly lower melting temperature compared to the racemate which
      was in accordance with its higher water solubility and its increased intrinsic
      dissolution rate. The thermograms of S-amlodipine besylate indicated that
      dehydration and melting occur at almost the same time and the dehydration event
      overlaps with the melting peak. Forced degradation tests conducted on both
      substances showed high levels of degradation into amlodipine related substance D
      as well as other impurities. Tablets prepared with S-AB, simulating originator's
      formulation, failed in stability tests due to drug incompatibility with calcium
      hydrogen phosphate. Therefore, a tablet formulation based on excipients which
      were confirmed compatible with S-AB was developed and optimized using full
      factorial design to obtain a dissolution profile comparative to the brand
      product. Stability studies conducted at 40  degrees C/75% relative humidity (RH)
      confirmed that appearance, drug content and drug release of the optimized tablet
      formulation remained within the recommended limits.

PMID- 24099555
TI  - [(18)F]-fluorodeoxyglucose positron emission tomography and computed tomography
      in response evaluation of oncolytic adenovirus treatments of patients with
      advanced cancer.
AB  - Computed tomography (CT) is the most commonly used radiological response
      evaluation method in contemporary oncology. However, it may not be optimally
      suitable for assessment of oncolytic virus treatments because of paradoxical
      inflammatory tumor swellings, which result from virus treatments, particularly
      when viruses are armed with immunostimulatory molecules. Here we investigated the
      prognostic utility of CT and [(18)F]-fluorodeoxyglucose (FDG) positron emission
      tomography (PET) in oncolytic virus treatments. We also investigated possible
      appearance of false-positive FDG signals in FDG-PET imaging of humans and
      hamsters treated with oncolytic adenoviruses. First, immunocompetent Syrian
      hamsters were treated with intratumoral adenovirus injections, tumor growth was
      followed up, and [(18)F]-FDG-uptake was quantitated with small animal PET/CT.
      Second, we describe a retrospective patient series, essentially 17 individual
      case reports, of advanced cancer patients treated with oncolytic adenoviruses in
      the context of an Advanced Therapy Access Program (ATAP) who underwent
      radiological response evaluation with both contrast-enhanced CT and FDG-PET.
      Third, we collected a retrospective case series of radiological response and
      survival data of 182 patients treated with oncolytic adenoviruses in ATAP to
      evaluate the prognostic reliability of CT and FDG-PET. Overall, responses in CT
      and FDG-PET correlated well with each other and were equally reliable as
      prognostic markers for long survival after oncolytic adenovirus treatment.
      Interestingly, we observed that new FDG-avid lymph nodes appearing in FDG-PET
      after virus treatments may represent inflammatory responses and therefore should
      not be interpreted as treatment failure in the absence of other signs or
      verification of disease progression. We also observed indications that FDG-PET
      might be more sensitive in detection of responses than tumor size.

PMID- 24099554
TI  - Adrenomedullin delivery in microsphere-scaffold composite for remodeling of the
      alveolar bone following tooth extraction: an experimental study in the rat.
AB  - BACKGROUND: Alveolar ridge resorption, as a significant problem in implant and
      restorative dentistry, has long been considered as an inevitable outcome
      following tooth extraction. Recently, adrenomedullin (ADM) is reported to be able
      to stimulate the proliferation and migration of various cells including
      osteoblasts. The purpose of this study was to investigate the influence of local
      ADM application in the tooth extraction socket in vivo. METHODS: Chitosan
      micropheres were developed by an emulsion-ionic cross-linking method for ADM
      delivery. Poly (L -lactic-co-glycolic) acid (PLGA) and nano-hydroxyapatite (nHA)
      were used to prepare scaffolds to contain the micrspheres with ADM. In vivo
      experiment was evaluated by transplanting the composite into the rat socket right
      after the incisor extraction. After 4, 8, 12 weeks implantation, radiographic and
      histological tests were carried out to evaluate the effect of released ADM on the
      alveolar bone. RESULTS: The microspheres had a spherical structure and a relative
      rough and uniform surface, and the particle size was under a normal distribution,
      with the average diameter of 38.59 MUm. The scaffolds had open and interconnected
      pores. In addition, the high porosity of the composite was 88.93%. Radiographic
      and histological examination revealed that the PLGA/nHA/CMs/ADM composite could
      accelerate the alveolar bone remodeling and reduce the residual ridge resorption
      compared with the PLGA/nHA/CMs scaffold. CONCLUSIONS: The results of this study
      suggest that local application of ADM has the potential to preserve the residual
      alveolar ridge and accelerate the alveolar bone remodeling.

PMID- 24099557
TI  - Built-in electric field-assisted surface-amorphized nanocrystals for high-rate
      lithium-ion battery.
AB  - High-power batteries require fast charge/discharge rates and high capacity
      besides safe operation. TiO2 has been investigated as a safer alternative
      candidate to the current graphite or incoming silicon anodes due to higher redox
      potentials in effectively preventing lithium deposition. However, its
      charge/discharge rates are reluctant to improve due to poor ion diffusion
      coefficients, and its capacity fades quickly with rate as only thinner surface
      layers can be effectively used in faster charge/discharge processes. Here, we
      demonstrate that surface-amorphized TiO2 nanocrystals greatly improve lithium-ion
      rechargeable battery performance: 20 times rate and 340% capacity improvement
      over crystalline TiO2 nanocrystals. This improvement is benefited from the built
      in electric field within the nanocrystals that induces much lower lithium-ion
      diffusion resistance and facilitates its transport in both insertion and
      extraction processes. This concept thus offers an innovative and general approach
      toward designing battery materials with better performance. 

PMID- 24099556
TI  - Genetic variations of E6 and long control region of human papillomavirus type 16
      from patients with cervical lesion in Liaoning, China.
AB  - BACKGROUND: High-risk human papillomavirus type 16 (HPV16) is a risk factor for
      cervical cancer. Previous studies suggest that polymorphisms in the E6 gene or
      the long control region(LCR)of HPV16 may alter the oncogenic potential of the
      virus. The aims of this study were to investigate the genetic variations of HPV16
      E6 gene and LCR in isolates from Chinese population and correlation of the E6 and
      LCR polymorphisms with disease status of infected patients. METHODS: HPV16
      positive endocervical specimens were collected from 304 women living in Northeast
      of China. Sequences of E6 gene and LCR were analyzed by PCR-sequencing. RESULTS:
      Two lineages were found in the populations, including EUR lineage and As lineage.
      Based on the HPV16 prototype, the most frequent variation in the E6 gene was
      T178A/G (48.7%), followed by mutations of G94A (12.2%) and T350G (9.9%). The rank
      orders of incidence of E6 variations in amino acid were as follows: D25E (46.3%),
      L83V (9.9%) and H78Y (4.3%). Nucleotide variations in LCR were found in all the
      304 isolates from HPV16 positive cervical samples. The most commonly observed LCR
      variations were the transition replacement G7193T, 7434CIns, G7521A and 7863ADel
      (100%). The As lineage was associated with HPV persistent infections and with
      disease status of >=CIN2,3. The EUR lineage variants showed a negative trend of
      association with the severity of >=CIN2,3. Among 41 variations found in LCR, 25
      (61.0%) were located at the binding sites for transcription factors. Occurrence
      of >=CIN2,3 was significantly associated with the mutations of R10G/L83V in E6
      and the C7294T co-variation in LCR, after adjusting for ages of infected
      patients. CONCLUSIONS: Associations between As lineage and HPV persistent
      infections, and with disease status of >=CIN2,3, and an association between the
      EUR lineage and negative trend of association with the severity of >=CIN2,3 were
      found in this study. An association between a co-variation of R10G/L83V in E6 and
      C7294T in LCR and an increased risk for developing CIN-2,3 was found in a HPV16
      infected population of Chinese women. These findings indicate that HPV16
      polymorphism influences development of CIN-2,3.

PMID- 24099558
TI  - Intimate partner violence and the CDC's best-evidence HIV risk reduction
      interventions.
AB  - OBJECTIVES: Intimate partner violence (IPV) is a prevalent health burden in the
      United States and is a risk factor for HIV (human immunodeficiency virus)
      transmission. Despite the association between IPV and HIV risk, IPV is often
      omitted from HIV prevention research and interventions. This review analyzes the
      Centers for Disease Control and Prevention's best-evidence HIV risk reduction
      interventions and their incorporation of IPV assessment, education and
      evaluation. DESIGN AND SAMPLE: The Centers for Disease Control and Prevention's
      best-evidence HIV risk reduction interventions (n = 44) were reviewed for
      inclusion of IPV content. RESULTS: Of the 44 best evidence interventions, 5
      addressed IPV. These 5 interventions were further examined for method,
      measurement and uniformity. CONCLUSIONS: Justification for IPV integration in HIV
      risk reduction programs is explored and supported by evidence-based research and
      practice.

PMID- 24099559
TI  - Two-step method of enzymatic synthesis of starch laurate in ionic liquids.
AB  - Enzymatic esterification of starch with long-chain fatty acid was investigated by
      using ionic liquids 1-butyl-3-methylimidazolium choride ([BMIm]Cl) and 1-butyl-3
      methylimidazolium tetrafluoroborate ([BMIm][BF4]) as reaction media. An
      industrial lipase produced by Candida rugosa was used to modify starch with
      lauric acid. The effect of reaction parameters such as the lipase dosage, the
      molar ratio of lauric acid/anhydroglucose unit (AGU) in starch, and the reaction
      temperature as well as the reaction time on the degree of substitution (DS) of
      long-chain fatty acid starch esters was studied. The maximum DS value was 0.171
      under the given conditions. The maximum solubility of high-amylose starch
      measured by turbidity was 11.0/100 g of [BMIm]Cl. The esterification products
      were confirmed according to Fourier transform infrared (FT-IR) and nuclear
      magnetic resonance (NMR) analysis. The morphological and crystallographic
      properties of native starch were largely disrupted during modification process as
      indicated by scanning electron microscopy (SEM) and X-ray diffraction (XRD) data.
      The thermal stability of the starch laurates was found to decrease compared to
      native starch. After reaction, the ionic liquid was effectively recycled and
      reused. This paper explores the potential of ionic liquids as solvent for the
      enzymatic synthesis of long-chain fatty acid starch esters. 

PMID- 24099560
TI  - BMP4, a new prognostic factor for glioma.
AB  - BACKGROUND: The expression status of bone morphogenetic protein 4 (BMP4) in
      gliomas is still unclear by now. We try to investigate the relationship between
      BMP4 expression and the biological behavior of gliomas in order to lay a
      foundation for the management of these tumors. METHODS: A total of 630 patients
      with glioma were enrolled in the study from January 2002 to January 2008. The
      expression status of BMP4 in gliomas was evaluated by RT-PCR and
      immunohistochemistry. The relationships between BMP4 expression and
      clinicopathological parameters and between BMP4 expression and prognosis were
      also studied. RESULTS: The expression of BMP4 in tumor tissues was significantly
      lower than that in the paracancer tissues at both mRNA and protein levels (P =
      0.01 and 0.001, respectively). Univariate analysis showed that BMP4 expression
      was closely related to extent of resection, Ki-67 expression, and the WHO grade
      (P = 0.001, 0.001, and 0.001, respectively), but it was not related to age, sex,
      or the Karnofsky Performance Status (KPS) score (P = 0.099, 0.472, and 0.201,
      respectively). Finally, Ki-67 expression and the WHO grade were found to be
      related to BMP4 expression using logistic regression (P = 0.001 and 0.001,
      respectively). Interestingly, we found that the expression of BMP4 was
      significantly related to distant glioma metastasis. Cox regression analysis
      identified the KPS score, extent of resection, Ki-67 expression, WHO grade, and
      BMP4 expression as independent prognostic factors (P = 0.044, 0.010, 0.002,
      0.001, and 0.001, respectively). CONCLUSIONS: BMP4 is differentially expressed in
      glioma patients and is closely related to the biological behavior of gliomas.
      BMP4 expression was found to be a strong predictor of distant metastasis and
      postoperative prognosis.

PMID- 24099561
TI  - Selection of reference genes for quantitative real-time PCR analysis in chicken
      embryo fibroblasts infected with avian leukosis virus subgroup J.
AB  - BACKGROUND: The selection of stably expressed reference genes is a prerequisite
      when evaluating gene expression, via real-time PCR, in cells in response to viral
      infections. The objective of our study was to identify suitable reference genes
      for mRNA expression analysis in chicken embryonic fibroblasts (CEF) after
      infection with avian leukosis virus subgroup J (ALV-J). FINDINGS: The expression
      levels of 11 potential reference genes in CEF infected with ALV-J were determined
      by real-time PCR. The expression stability of these genes were analyzed and
      ranked using the geNorm tool. Analysis indicated that the genes RPL30 (ribosomal
      protein L30) and SDHA (succinate dehydrogenase complex, subunit A) were the most
      stably expressed genes in the ALV-J infected CEF. CONCLUSIONS: The RPL30 and SDHA
      were deemed suitable for use as reference genes for real-time PCR analysis of
      mRNA gene expression during ALV-J infection, whereas commonly used ACTB and GAPDH
      are unsuitable to be reference genes.

PMID- 24099562
TI  - Hiding or hospitalising? On dilemmas of pregnancy management in East Cameroon.
AB  - Current international debates and policies on safe motherhood mainly propose
      biomedical interventions to reduce the risks during pregnancy and delivery. Yet,
      the conceptualisations of risk that underlie this framework may not correspond
      with local perceptions of reproductive dangers; consequently, hospital services
      may remain underutilised. Inspired by a growing body of anthropological
      literature exploring local fertility-related fears, and drawing on 15 months of
      fieldwork, this paper describes ideas about risky reproduction and practices of
      pregnancy protection in a Cameroonian village. It shows that social and
      supernatural threats to fertility are deemed more significant than the physical
      threats of fertility stressed at the (inter)national level. To protect their
      pregnancies from those social and supernatural influences, however, women take
      very physical measures. It is in this respect that biomedical interventions,
      physical in their very nature, do connect to local methods of pregnancy
      management. Furthermore, some pregnant women purposefully deploy hospital care in
      an attempt to reduce relational uncertainties. Explicit attention to the
      intersections of the social and the physical, and of the supernatural and the
      biomedical, furthers anthropological knowledge on fertility management and offers
      a starting point for more culturally sensitive safe motherhood interventions. 

PMID- 24099563
TI  - Neutrophils from critically ill septic patients mediate profound loss of
      endothelial barrier integrity.
AB  - INTRODUCTION: Sepsis is characterized by systemic immune activation and
      neutrophil-mediated endothelial barrier integrity compromise, contributing to end
      organ dysfunction. Studies evaluating endothelial barrier dysfunction induced by
      neutrophils from septic patients are lacking, despite its clinical significance.
      We hypothesized that septic neutrophils would cause characteristic patterns of
      endothelial barrier dysfunction, distinct from experimental stimulation of normal
      neutrophils, and that treatment with the immunomodulatory drug beta-glucan would
      attenuate this effect. METHODS: Blood was obtained from critically ill septic
      patients. Patients were either general surgery patients (Primary Sepsis (PS)) or
      those with sepsis following trauma (Secondary Sepsis (SS)). Those with acute
      respiratory distress syndrome (ARDS) were identified. Healthy volunteers served
      as controls. Neutrophils were purified and aliquots were untreated, or treated
      with fMLP or beta-glucan. Endothelial cells were grown to confluence and
      activated with tissue necrosis factor (TNF)-alpha . Electric Cell-substrate
      Impedance Sensing (ECIS) was used to determine monolayer resistance after
      neutrophils were added. Groups were analyzed by two-way analysis of variance
      (ANOVA). RESULTS: Neutrophils from all septic patients, as well as fMLP-normal
      neutrophils, reduced endothelial barrier integrity to a greater extent than
      untreated normal neutrophils (normalized resistance of cells from septic patients
      at 30 mins = 0.90 +/- 0.04; at 60 mins = 0.73 +/- 0.6 and at 180 mins = 0.56 +/-
      0.05; p < 0.05 vs normal). Compared to untreated PS neutrophils, fMLP-treated PS
      neutrophils caused further loss of barrier function at all time points; no
      additive effect was noted in stimulation of SS neutrophils beyond 30 min.
      Neutrophils from ARDS patients caused greater loss of barrier integrity than
      those from non-ARDS patients, despite similarities in age, sex, septic source,
      and neutrophil count. Neutrophils obtained after resolution of sepsis caused less
      barrier dysfunction at all time points. beta-glucan treatment of septic patients'
      neutrophils attenuated barrier compromise, rendering the effect similar to that
      induced by neutrophils obtained once sepsis had resolved. CONCLUSIONS:
      Neutrophils from septic patients exert dramatic compromise of endothelial barrier
      integrity. This pattern is mimicked by experimental activation of healthy
      neutrophils. The effect of septic neutrophils on the endothelium depends upon the
      initial inflammatory event, correlates with organ dysfunction and resolution of
      sepsis, and is ameliorated by beta-glucan.

PMID- 24099565
TI  - Exon deletion patterns of the dystrophin gene in 82 Vietnamese Duchenne/Becker
      muscular dystrophy patients.
AB  - Duchenne and Becker muscular dystrophies (DMD/BMD) are the most common inherited
      muscle diseases caused by mutations in the dystrophin gene. The reading frame
      rule explains the genotype-phenotype relationship in DMD/BMD. In Vietnam,
      extensive mutation analysis has never been conducted in DMD/BMD. Here, 152
      Vietnamese muscular dystrophy patients were examined for dystrophin exon deletion
      by amplifying 19 deletion-prone exons and deletion ends were confirmed by
      dystrophin cDNA analysis if necessary. The result was that 82 (54%) patients were
      found to have exon deletions, thus confirming exact deletion ends. A further
      result was that 37 patterns of deletion were classified. Deletions of exons 45-50
      and 49-52 were the most common patterns identified, numbering six cases each
      (7.3%). The reading frame rule explained the genotype-phenotype relationship, but
      not five (6.1%) DMD cases. Each of five patients had deletions of exons 11-27 in
      common. The applicability of the therapy producing semifunctional in frame mRNA
      in DMD by inducing skipping of a single exon was examined. Induction of exon 51
      skipping was ranked at top priority, since 16 (27%) patients were predicted to
      have semifunctional mRNA skipping. Exons 45 and 53 were the next ranked, with 12
      (20%) and 11 (18%) patients, respectively. The largest deletion database of the
      dystrophin gene, established in Vietnamese DMD/BMD patients, disclosed a strong
      indication for exon-skipping therapy.

PMID- 24099566
TI  - Membrane-based, sedimentation-assisted plasma separator for point-of-care
      applications.
AB  - Often, high-sensitivity, point-of-care (POC) clinical tests, such as HIV viral
      load, require large volumes of plasma. Although centrifuges are ubiquitously used
      in clinical laboratories to separate plasma from whole blood, centrifugation is
      generally inappropriate for on-site testing. Suitable alternatives are not
      readily available to separate the relatively large volumes of plasma from
      milliliters of blood that may be needed to meet stringent limit-of-detection
      specifications for low-abundance target molecules. We report on a simple-to-use,
      low-cost, pump-free, membrane-based, sedimentation-assisted plasma separator
      capable of separating a relatively large volume of plasma from undiluted whole
      blood within minutes. This plasma separator consists of an asymmetric, porous,
      polysulfone membrane housed in a disposable chamber. The separation process takes
      advantage of both gravitational sedimentation of blood cells and size exclusion
      based filtration. The plasma separator demonstrated a "blood in-plasma out"
      capability, consistently extracting 275 +/- 33.5 MUL of plasma from 1.8 mL of
      undiluted whole blood within less than 7 min. The device was used to separate
      plasma laden with HIV viruses from HIV virus-spiked whole blood with recovery
      efficiencies of 95.5% +/- 3.5%, 88.0% +/- 9.5%, and 81.5% +/- 12.1% for viral
      loads of 35,000, 3500, and 350 copies/mL, respectively. The separation process is
      self-terminating to prevent excessive hemolysis. The HIV-laden plasma was then
      injected into our custom-made microfluidic chip for nucleic acid testing and was
      successfully subjected to reverse-transcriptase loop-mediated isothermal
      amplification (RT-LAMP), demonstrating that the plasma is sufficiently pure to
      support high-efficiency nucleic acid amplification.

PMID- 24099567
TI  - Cytokines in terms of QSAR. Review, evaluation and comparative studies.
AB  - Cytokines represent a class of chemical factors that act as mediators in the
      complex biological response of inflammation, potentially implicated in various
      diseases. Therefore, selective inhibition or antagonism of cytokines is a target
      of anti-inflammatory drug design. The QSAR (Quantitative Structure-Activity
      Relationships) analysis presented here attempts to identify the structural
      features and physicochemical properties that are significant for cytokine
      antagonists or inhibitors and in particular of i) interleukin-5 (IL-5), ii)
      interleukin-6 (IL-6) and iii) of the chemotactic cytokine (chemokine) interleukin
      8 (IL-8). Firstly, a historical aspect of the limited published QSARs is
      discussed and then a 2D-QSAR analysis was carried out for 26 data sets of
      compounds using the C-QSAR program of Biobyte. In six cases hydrophobicity
      appeared to be important. Steric factors in the form of overall molar
      refractivity (CMR), molar refractivity of the substituent (MR), molar volume
      (MgVol), Taft's Es constant and the sterimol parameters B1 and B5 have a
      significant impact on biological activity in most of the derived equations
      whereas electronic parameters as sigmap, sigmam or Sigmasigma appeared in five
      cases. 

PMID- 24099564
TI  - Urodynamic investigation by telemetry in Beagle dogs: validation and effects of
      oral administration of current urological drugs: a pilot study.
AB  - BACKGROUND: Vesico-urethral function may be evaluated in humans and dogs by
      conventional urodynamic testing (cystometry and urethral pressure profilometry)
      or by electromyography. These techniques are performed under general anaesthesia
      in dogs. However, anaesthesia can depress bladder and urethral pressures and
      inhibit the micturition reflex. The primary objective of this pilot study was to
      evaluate the use of telemetry for urodynamic investigation in dogs. We also aimed
      to determine the applicability of telemetry to toxicologic studies by assessing
      the repeatability of telemetric recordings. RESULTS: Conventional diuresis
      cystometry was performed in six continent adult female Beagle dogs prior to
      surgical implantation of telemetric and electromyographic devices. In the first
      phase of the telemetric study, continuous recordings were performed over 8 days
      and nights. Abdominal, intravesical and detrusor threshold pressures (Pdet th),
      voided volume (Vv), urethral smooth muscle electrical activity and involuntary
      detrusor contractions (IDC) were measured during the bladder filling phase and
      during micturition episodes.Vv recorded during telemetry was significantly lower
      than bladder volume obtained by diuresis cystometry. Repeatability of telemetric
      measurements was greater for observations recorded at night. IDC frequency and
      Pdet th were both lower and Vv was higher at night compared to values recorded
      during daytime.In the second phase of the telemetric study, phenylpropanolamine,
      oestriol, bethanechol, oxybutynin or duloxetine were administered orally for 15
      days. For each drug, continuous recordings were performed overnight for 12 hours
      on days 0, 1, 8 and 15. Electromyographic urethral activity was significantly
      increased 8 days after oestriol or duloxetine administration. No significant
      changes in bladder function were observed at any time point. CONCLUSIONS: In
      dogs, the high repeatability of nocturnal telemetric recordings indicates that
      this technique could provide more informative results for urologic research.
      Urethral smooth muscle electrical activity appears to be modified by
      administration of drugs with urethral tropism. In this pilot telemetric study,
      bladder function was not affected by oral administration of urological drugs at
      their recommended clinical dosages. Experimental studies, (pharmacokinetic and
      pharmacodynamic) and clinical studies are warranted to further define the effects
      of these drugs on vesico-urethral function in dogs.

PMID- 24099568
TI  - Association of pregnancy-associated plasma protein-A gene polymorphism with
      ischemic stroke in northern Chinese Han population.
AB  - OBJECTIVES: The pregnancy-associated plasma protein-A (PAPP-A), belonging to the
      metalloproteinase superfamily, plays an important role in destabilization of
      atherosclerotic plaques. The aim of this study is to evaluate whether PAPP-A gene
      polymorphism is associated with the risk of ischemic stroke (IS) in northern
      Chinese Han populations. METHODS: A total of 368 patients with IS and 374 aged
      matched healthy controls in a Chinese Han population were included in the case
      control study. The single-nucleotide polymorphism (SNP) IVS6+95 (rs13290387) in
      the PAPP-A gene was analyzed by the polymerase chain reaction-ligation detection
      reaction (PCR-LDR) method. RESULTS: Compared with the GG+CG genotype, the
      frequencies of the CC genotype of IVS6+95 (rs13290387) in the patients with IS
      were significantly higher than those in the controls (P  =  0.026). After
      adjusting the confounding risk factors of IS (age, gender, smoking, alcohol
      drinking, hypertension, diabetes mellitus, and hyperlipidemia) by the
      multivariate logistic analysis, this significant correlation still remained (P  =
      0.010). DISCUSSION: The CC genotype of IVS6+95 (rs13290387) was associated with
      increased incidence of IS in northern Chinese Han populations. This is an initial
      study to indicate that PAPP-A (rs13290387) might contribute to IS susceptibility
      in northern Chinese Han populations.

PMID- 24099569
TI  - Chemistry of dark clouds: databases, networks, and models.

PMID- 24099571
TI  - A focus on partial knee replacement. Introduction.

PMID- 24099570
TI  - Inadequacy of tissue microarrays for the immunohistochemical detection of cancer
      stem cells in solid tumors: a viewpoint.

PMID- 24099572
TI  - Oxford phase 3 unicompartmental knee arthroplasty in Japan--clinical results in
      greater than one thousand cases over ten years.
AB  - There are few reports of the Oxford unicompartmental knee arthroplasty (UKA)
      survival rate in Asia. This study describes outcomes of 1279 Oxford UKAs for
      Japanese patients. The mean follow-up was 5.2 years. We divided patients into two
      groups based on preoperative indications (extended indications group and strict
      indications group). The Oxford knee score improved from 22.3 to 40.8 (P=0.041).
      The 10-year survival rate using revision was 95%. A total of 25 UKAs (2.0%)
      required revision. The most common reason was subsidence of tibial component. The
      5-year cumulative survival rate of the strict indications group was significantly
      higher than that of the extended indications group (99.1% vs. 93.8%, P<0.001).
      When we followed inclusion criteria strictly, good clinical results were achieved
      in Asia.

PMID- 24099573
TI  - Unicompartmental knee arthroplasty enables near normal gait at higher speeds,
      unlike total knee arthroplasty.
AB  - Top walking speed (TWS) was used to compare UKA with TKA. Two groups of 23
      patients, well matched for age, gender, height and weight and radiological
      severity were recruited based on high functional scores, more than twelve months
      post UKA or TKA. These were compared with 14 preop patients and 14 normal
      controls. Their gait was measured at increasing speeds on a treadmill
      instrumented with force plates. Both arthroplasty groups were significantly
      faster than the preop OA group. TKA patients walked substantially faster than any
      previously reported series of knee arthroplasties. UKA patients walked 10% faster
      than TKA, although not as fast as the normal controls. Stride length was 5%
      greater and stance time 7% shorter following UKA - both much closer to normal
      than TKA. Unlike TKA, UKA enables a near normal gait one year after surgery. 

PMID- 24099574
TI  - Self-assembled monolayer films derived from tridentate cyclohexyl adsorbates with
      alkyl tailgroups of increasing chain length.
AB  - Tridentate cyclohexyl-based alkanethiolate SAMs generated from a series of
      adsorbates of the form R3C6H6(CH2SH)3, where R = -(CH2)nH and n = 3, 8, and 13
      (3CnCyTSH), were examined. Characterization of the SAMs by X-ray photoelectron
      spectroscopy (XPS) revealed that all sulfur atoms of the tridentate adsorbates
      were bound to the surface of gold, and that the tailgroups were in general less
      densely packed than the SAM derived from octadecanethiol (C18SH). For each of the
      SAMs, the relative molecular coverage on the surface was estimated from the XPS
      derived C1s/Au4f ratios. The trend in conformational order for these SAMs as
      determined by the surface interactions with contacting liquids and the relative
      crystallinity of the alkyl chains as revealed by the PM-IRRAS spectra were found
      to decrease as follows: C18SH >> 3C13CyTSH > 3C8CyTSH > 3C3CyTSH. A preliminary
      study of the thermal stability of the SAMs as evaluated by XPS indicates that the
      SAM generated from the cyclohexyl-based adsorbate with the longest alkyl chain,
      3C13CyTSH, is markedly more stable than the SAM generated from C18SH. Overall,
      the results suggest that the stability of the SAMs are influenced by both the
      length of the alkyl chains and the chelate effect associated with the tridentate
      adsorbates.

PMID- 24099575
TI  - The new French 2010 Rabbit Hemorrhagic Disease Virus causes an RHD-like disease
      in the Sardinian Cape hare (Lepus capensis mediterraneus).
AB  - Lagovirus is an emerging genus of Caliciviridae, which includes the Rabbit
      Hemorrhagic Disease Virus (RHDV) of rabbits and the European brown hare syndrome
      virus (EBHSV) of hares that cause lethal hepatitis. In 2010, a new RHDV related
      virus (RHDV2) with a unique genetic and antigenic profile and lower virulence was
      identified in France in rabbits. Here we report the identification of RHDV2 as
      the cause in Sardinia of several outbreaks of acute hepatitis in rabbits and Cape
      hare (Lepus capensis mediterraneus). This is the first account of a lagovirus
      that causes fatal hepatitis in both rabbits and hares. 

PMID- 24099576
TI  - Dominance of Haemophilus influenzae in ear discharge from Indigenous Australian
      children with acute otitis media with tympanic membrane perforation.
AB  - BACKGROUND: Indigenous Australian children living in remote communities
      experience high rates of acute otitis media with tympanic membrane perforation
      (AOMwiP). Otitis media in this population is associated with dense nasopharyngeal
      colonization of three primary otopathogens; Haemophilus influenzae, Streptococcus
      pneumoniae and Moraxella catarrhalis. Little is known about the relative
      abundance of these pathogens during infection. The objective of this study was to
      estimate the abundance and concordance of otopathogens in ear discharge and
      paired nasopharyngeal swabs from children with AOMwiP (discharge of not more than
      6 weeks' duration and perforation size <2%). METHODS: Culture and quantitative
      PCR (qPCR) estimation of H. influenzae, S. pneumoniae, M. catarrhalis and total
      bacterial load were performed on paired nasopharyngeal and ear discharge swabs
      from 55 Indigenous children with AOMwiP aged 3.5 - 45.6 months and resident in
      remote communities. RESULTS: By culture, H. influenzae, S. pneumoniae, and M.
      catarrhalis were detected in 80%, 84% and 91% of nasopharyngeal swabs, and 49%,
      33% and 4% of ear discharge swabs, respectively. Using qPCR, H. influenzae, S.
      pneumoniae, and M. catarrhalis were detected in 82%, 82%, and 93% of
      nasopharyngeal swabs, and 89%, 41% and 18% of ear discharge swabs, respectively.
      Relative abundance of H. influenzae in ear discharge swabs was 0-68% of the total
      bacterial load (median 2.8%); whereas S. pneumoniae and M. catarrhalis relative
      abundances were consistently <2% of the total bacterial load. S. pneumoniae and
      M. catarrhalis abundances were significantly lower in ear discharge compared with
      nasopharyngeal swabs (p = 0.001, p < 0.001); no significant difference was
      observed in H. influenzae mean abundance at the two sites. CONCLUSIONS: H.
      influenzae was the dominant otopathogen detected in ear discharge swabs collected
      from children with AOMwiP. High prevalence and abundance of S. pneumoniae and M.
      catarrhalis in the nasopharynx did not predict ear discharge prevalence and
      abundances of these pathogens. PCR was substantially more sensitive than culture
      for ear discharge, and a necessary adjunct to standard microbiology. Quantitative
      methods are required to understand species abundance in polymicrobial infections
      and may be needed to measure accurately the microbiological impact of
      interventions and to provide a better understanding of clinical failure in these
      children.

PMID- 24099578
TI  - I see/hear what you mean: semantic activation in visual word recognition depends
      on perceptual attention.
AB  - How does the meaning of a word affect how quickly we can recognize it? Accounts
      of visual word recognition allow semantic information to facilitate performance
      but have neglected the role of modality-specific perceptual attention in
      activating meaning. We predicted that modality-specific semantic information
      would differentially facilitate lexical decision and reading aloud, depending on
      how perceptual attention is implicitly directed by each task. Large-scale
      regression analyses showed the perceptual modalities involved in representing a
      word's referent concept influence how easily that word is recognized. Both
      lexical decision and reading-aloud tasks direct attention toward vision, and are
      faster and more accurate for strongly visual words. Reading aloud additionally
      directs attention toward audition and is faster and more accurate for strongly
      auditory words. Furthermore, the overall semantic effects are as large for
      reading aloud as lexical decision and are separable from age-of-acquisition
      effects. These findings suggest that implicitly directing perceptual attention
      toward a particular modality facilitates representing modality-specific
      perceptual information in the meaning of a word, which in turn contributes to the
      lexical decision or reading-aloud response.

PMID- 24099577
TI  - TNF induces the expression of the sialyltransferase ST3Gal IV in human bronchial
      mucosa via MSK1/2 protein kinases and increases FliD/sialyl-Lewis(x)-mediated
      adhesion of Pseudomonas aeruginosa.
AB  - We have shown previously that the pro-inflammatory cytokine TNF (tumour necrosis
      factor) could drive sLe(x) (sialyl-Lewis(x)) biosynthesis through the up
      regulation of the BX transcript isoform of the ST3GAL4 (ST3 beta-galactoside
      alpha-2,3-sialyltransferase 4) sialyltransferase gene in lung epithelial cells
      and human bronchial mucosa. In the present study, we show that the TNF-induced up
      regulation of the ST3GAL4 BX transcript is mediated by MSK1/2 (mitogen- and
      stress-activated kinase 1/2) through the ERK (extracellular-signal-regulated
      kinase) and p38 MAPK (mitogen-activated protein kinase) pathways, and increases
      sLe(x) expression on high-molecular-mass glycoproteins in inflamed airway
      epithelium. We also show that the TNF-induced sLe(x) expression increases the
      adhesion of the Pseudomonas aeruginosa PAO1 and PAK strains to lung epithelial
      cells in a FliD-dependent manner. These results suggest that ERK and p38 MAPK,
      and the downstream kinase MSK1/2, should be considered as potential targets to
      hamper inflammation, bronchial mucin glycosylation changes and P. aeruginosa
      binding in the lung of patients suffering from lung diseases such as chronic
      bronchitis or cystic fibrosis.

PMID- 24099579
TI  - Lanthanides and quantum dots as Forster resonance energy transfer agents for
      diagnostics and cellular imaging.
AB  - Luminescent lanthanide labels (LLLs) and semiconductor quantum dots (QDs) are two
      very special classes of (at least partially) inorganic fluorophores, which
      provide unique properties for Forster resonance energy transfer (FRET). FRET is
      an energy-transfer process between an excited donor fluorophore and a ground
      state acceptor fluorophore in close proximity (approximately 1-20 nm), and
      therefore it is extremely well suited for biosensing applications in optical
      spectroscopy and microscopy. Within this cogent review, we will outline the main
      photophysical advantages of LLLs and QDs and their special properties for FRET.
      We will then focus on some recent applications from the FRET biosensing
      literature using LLLs as donors and QDs as donors and acceptors in combination
      with several other fluorophores. Recent examples of combining LLLs and QDs for
      spectral and temporal multiplexing from single-step to multistep FRET demonstrate
      the versatile and powerful biosensing capabilities of this unique FRET pair. As
      this review is published in the Forum on Imaging and Sensing, we will also
      present some new results of our groups concerning LLL-based time-gated cellular
      imaging with optically trifunctional antibodies and LLL-to-QD FRET-based
      homogeneous sandwich immunoassays for the detection of carcinoembryonic antigen. 

PMID- 24099580
TI  - The role of social engagement and identity in community mobility among older
      adults aging in place.
AB  - The purpose of this study was to understand how neighbourhoods - as physical and
      social environments - influence community mobility. Seeking an insider's
      perspective, the study employed an ethnographic research design. Immersed within
      the daily lives of 6 older adults over an 8-month period, auditory, textual, and
      visual data was collected using the "go-along" interview method. During these
      interviews, the researcher accompanied participants on their natural outings
      while actively exploring their physical and social practices by asking questions,
      listening, and observing. Findings highlight a process of community mobility that
      is complex, dynamic and often difficult as participant's ability and willingness
      to journey into their neighborhoods were challenged by a myriad of individual and
      environmental factors that changed from one day to the next. Concerned in
      particular with the social environment, final analysis reveals how key social
      factors - social engagement and identity - play a critical role in the community
      mobility of older adults aging in place. IMPLICATIONS FOR REHABILITATION:
      Identity and social engagement are important social factors that play a role in
      community mobility. The need for social engagement and the preservation of
      identity are such strong motivators for community mobility that they can "trump"
      poor health, pain, functional ability and hazardous conditions. To effectively
      promote community mobility, the social lives and needs of individuals must be
      addressed.

PMID- 24099581
TI  - The risk of falling in young adults with neurological conditions: a systematic
      review.
AB  - PURPOSE: To review systematically the literature on fall risk factors for young
      patients affected by neurological disorders. METHOD: A systematic search of all
      primary research-based literature on risk factors for falls or fall
      characteristics in young adults (mean age <55 years) published prior to July 2012
      was conducted using 11 databases. Studies that focused on fall risk screening
      tools, fear of falling or interventions for fall prevention were excluded. Two
      reviewers independently agreed on eligibility and methodological quality and
      extracted data. RESULTS: Twenty-three final studies were selected, including 21
      observational studies; one randomised controlled trial and one qualitative study.
      An average of 50.2% of the 2776 total participants experienced at least one fall.
      Among the multiple risk factors studied, a reduced performance in balance and
      gait was consistently associated with falls, while the contribution of single
      physical and cognitive impairments was variable in different populations. Walking
      aids, wheelchair characteristics and environmental hazards are significant
      environmental risk factors. The heterogeneity of the assessment tools used to
      measure risk factors limited comparison across studies. CONCLUSION: Falling is a
      common problem among young patients affected by neurological disorders, although
      the risk of falling for a specific individual is difficult to predict and the
      risk of a severe fall-related injury has not yet been established. IMPLICATIONS
      FOR REHABILITATION: Young patients with impaired gait and balance or medium to
      severe motor disability appear to be at increased risk of falling. Patients who
      are relatively independent and still participating in challenging activities have
      an increased exposure to fall-risk. Walking aids, wheelchair characteristics and
      environmental hazards are significant environmental risk factors. These risk
      factors should be monitored closely in the young neurological population to help
      prevent falls.

PMID- 24099582
TI  - English health visitors' perceptions of conducting indoor environmental
      assessments: barriers and facilitators.
AB  - OBJECTIVES: The aim of this qualitative research was to explore health visitors'
      perceptions of assessing their clients' homes and providing evidence-informed
      advice about environmental health. DESIGN AND SAMPLE: Between 2004 and 2007, an
      explorative study was conducted in Plymouth, England, during which interviews
      were held with health visitors trained to conduct environmental assessments in
      combination with routine visits. MEASURES: Face-to-face, semi-structured
      interviews were conducted. Content analysis was used to explore emergent themes.
      RESULTS: The health visitors perceived that assessing the indoor environment was
      relevant to their role; however, conducting environmental measurements within
      routine visits was not feasible. The main barriers were the changing roles of
      health visitors (reducing time available), the time implications of being
      perceived as an environmental expert, and the impact on clients, such as raising
      expectations, imposing opinions on the state of clients' homes, and expecting
      clients to implement advice. Facilitators included the natural link to health
      visitors' roles, the ability to provide evidence of an environmental risk, and
      the satisfaction of observing clients implementing advice. CONCLUSIONS: Health
      visitors lacked propositional knowledge on the indoor environment, highlighting a
      need for more training. Access to an environmental assessment system increased
      the health visitors' confidence in dealing with indoor environmental issues.

PMID- 24099583
TI  - Dielectrophoresis-assembled zeolitic imidazolate framework nanoparticle-coupled
      resonators for highly sensitive and selective gas detection.
AB  - This work reports on zeolitic imidazolate framework (ZIF)-coupled microscale
      resonators for highly sensitive and selective gas detection. The combination of
      microscale resonators and nanoscale materials simultaneously permits the benefit
      of larger capture area for adsorption from the resonator and enhanced surface
      adsorption capacity from the nanoscale ZIF structure. Dielectrophoresis (DEP) was
      demonstrated as a novel method for directly assembling concentrated ZIF
      nanoparticles on targeted regions of silicon resonant sensors. As part of the
      dielectrophoretic assembly process, the first ever measurements of the Clausius
      Mossotti factor for ZIFs were conducted to determine optimal conditions for DEP
      assembly. The first ever real-time adsorption measurements of ZIFs were also
      performed to investigate the possibility of inherent gas selectivity. The ZIF
      coupled resonators demonstrated sensitivity improvement up to 150 times over a
      bare silicon resonator with identical dimensions, and real-time adsorption
      measurements of ZIFs revealed different adsorption time constants for IPA and
      CO2. 

PMID- 24099584
TI  - Acceptable noise level (ANL) and real-world hearing-aid success in Taiwanese
      listeners.
AB  - OBJECTIVE: The objective of this prospective study was to investigate the
      relationship between acceptable noise level (ANL), which was measured using
      Taiwanese and the international speech test signal (ISTS), and real-world hearing
      aid success for listeners who were representative of the population commonly seen
      in clinics. DESIGN: Unaided ANLs were measured pre-hearing-aid fitting. Hearing
      aid success was assessed three months post-fitting using the international
      outcome inventory for hearing aids (IOI-HA) and a hearing-aid use questionnaire.
      STUDY SAMPLE: Eighty adults with hearing impairment completed the study. RESULTS:
      Both Taiwanese and ISTS ANLs were significantly associated with hearing-aid
      success, with higher ANLs suggesting poorer outcomes. However, the ANL's
      prediction accuracy for the probability of hearing-aid success was either much
      lower than that suggested by some literature, or was not much different from that
      of simply predicting all listeners as successful users. CONCLUSIONS: The current
      study suggested the possibility of using ANL to predict hearing-aid success.
      However, the usefulness of ANL as a clinical tool is unlikely to be as great as
      indicated by the literature.

PMID- 24099585
TI  - Phase I dose-finding study of cabazitaxel administered weekly in patients with
      advanced solid tumours.
AB  - BACKGROUND: Cabazitaxel is approved in patients with metastatic hormone
      refractory prostate cancer previously treated with a docetaxel-containing
      regimen. This study evaluated a weekly cabazitaxel dosing regimen. Primary
      objectives were to report dose-limiting toxicities (DLTs) and to determine the
      maximum tolerated dose (MTD). Efficacy, safety and pharmacokinetics were
      secondary objectives. METHODS: Cabazitaxel was administered weekly (1-hour
      intravenous infusion at 1.5-12 mg/m2 doses) for the first 4 weeks of a 5-week
      cycle in patients with solid tumours. Monitoring of DLTs was used to determine
      the MTD and the recommended weekly dose. RESULTS: Thirty-one patients were
      enrolled. Two of six patients experienced DLTs at 12 mg/m2, which was declared
      the MTD. Gastrointestinal disorders were the most common adverse event. Eight
      patients developed neutropenia (three >= Grade 3); one occurrence of febrile
      neutropenia was reported. There were two partial responses (in breast cancer) and
      13 patients had stable disease (median duration of 3.3 months). Increases in
      C(max) and AUC(0-t) were dose proportional for the 6-12 mg/m2 doses. CONCLUSION:
      The MTD of weekly cabazitaxel was 12 mg/m2 and the recommended weekly dose was 10
      mg/m2. The observed safety profile and antitumour activity of cabazitaxel were
      consistent with those observed with other taxanes in similar dosing regimens.
      TRIAL REGISTRATION: The study was registered with ClinicalTrials.gov as
      NCT01755390.

PMID- 24099586
TI  - Antibacterial activity of Nymphaea nouchali (Burm. f) flower.
AB  - BACKGROUND: The present work aimed to find out the antibacterial activity of
      Nymphaea nouchali flower on human and plant pathogenic bacteria. METHODS:
      Antibacterial potency of methanol, acetone, ethyl acetate and petroleum spirit
      extracts of Nymphaea nouchali flower has been tested against four human
      pathogenic bacteria Bacillus subtilis (FO 3026) Escherichia coli (IFO 3007),
      Klebsiella pneumonia (ATTC 10031) and Sarcina lutea (IFO 3232) and one plant
      pathogenic bacterium Xanthomonas campestris (IAM 1671) by disc diffusion assay.
      Zone of inhibition produced by different extracts against the test bacteria was
      measured and compared with standard antibiotic disc. RESULTS: Methanol extract
      possessed better antibacterial activity against two pathogenic bacteria, B.
      subtilis (FO 3026) and S. lutea (IFO 3232) than commercial antibiotic nalidixic
      acid. Acetone extract showed moderate sensitivity whereas B. subtilis (FO 3026),
      S. lutea (IFO 3232) and X. campestris (IAM 1671) showed resistance to ethyl
      acetate and petroleum spirit extracts. The minimum inhibitory concentrations of
      various extracts were ranged between 128-2048 MUgml-1. CONCLUSIONS: Nymphaea
      nouchali flower could be a potential candidate for future development of novel
      broad spectrum antibacterial herbal formulation.

PMID- 24099587
TI  - Looming motion primes the visuomotor system.
AB  - A wealth of evidence now shows that human and animal observers display greater
      sensitivity to objects that move toward them than to objects that remain static
      or move away. Increased sensitivity in humans is often evidenced by reaction
      times that increase in rank order from looming, to receding, to static targets.
      However, it is not clear whether the processing advantage enjoyed by looming
      motion is mediated by the attention system or the motor system. The present study
      investigated this by first examining whether sensitivity is to looming motion per
      se or to certain monocular or binocular cues that constitute stereoscopic motion
      in depth. None of the cues accounted for the looming advantage. A perceptual
      measure was then used to examine performance with minimal involvement of the
      motor system. Results showed that looming and receding motion were equivalent in
      attracting attention, suggesting that the looming advantage is indeed mediated by
      the motor system. These findings suggest that although motion itself is
      sufficient for attentional capture, motion direction can prime motor responses.

PMID- 24099588
TI  - Angular declination and the dynamic perception of egocentric distance.
AB  - The extraction of the distance between an object and an observer is fast when
      angular declination is informative, as it is with targets placed on the ground.
      To what extent does angular declination drive performance when viewing time is
      limited? Participants judged target distances in a real-world environment with
      viewing durations ranging from 36-220 ms. An important role for angular
      declination was supported by experiments showing that the cue provides
      information about egocentric distance even on the very first glimpse, and that it
      supports a sensitive response to distance in the absence of other useful cues.
      Performance was better at 220-ms viewing durations than for briefer glimpses,
      suggesting that the perception of distance is dynamic even within the time frame
      of a typical eye fixation. Critically, performance in limited viewing trials was
      better when preceded by a 15-s preview of the room without a designated target.
      The results indicate that the perception of distance is powerfully shaped by
      memory from prior visual experience with the scene. A theoretical framework for
      the dynamic perception of distance is presented.

PMID- 24099589
TI  - Establishment of an attentional set via statistical learning.
AB  - The ability to overcome attentional capture and attend goal-relevant information
      is typically viewed as a volitional, effortful process that relies on the
      maintenance of current task priorities or "attentional sets" in working memory.
      However, the visual system possesses statistical learning mechanisms that can
      incidentally encode probabilistic associations between goal-relevant objects and
      the attributes likely to define them. Thus, it is possible that statistical
      learning may contribute to the establishment of a given attentional set and
      modulate the effects of attentional capture. Here we provide evidence for such a
      mechanism, showing that implicitly learned associations between a search target
      and its likely color directly influence the ability of a salient color precue to
      capture attention in a classic attentional capture task. This indicates a novel
      role for statistical learning in the modulation of attentional capture, and
      emphasizes the role that this learning may play in goal-directed attentional
      control more generally.

PMID- 24099591
TI  - Evaluation of a commercial vaccine against avian poxvirus in turkeys kept in the
      backyard system in the state of Yucatan, Mexico.
AB  - One hundred and sixty 1-month-old turkey poults were delivered to 40 households
      in four communities of the State of Yucatan, Mexico. The poults were divided into
      two populations, one vaccinated and the other non-vaccinated against avian pox.
      During three months, monthly visits were carried out in order to monitor the
      appearance of lesions suggesting avian pox in the birds delivered. Each turkey
      was clinically examined, searching for characteristic avian pox lesions that were
      classified according to the degree of severity observed. The true incidence rate
      and the cumulative incidence rate of avian pox were determined and the true
      incidence and cumulative incidence rates of mortality were determined and the
      relative risks calculated. The true incidence rates for avian pox in vaccinated
      and non-vaccinated birds were 1.5 and 1.47 respectively. The cumulative incidence
      rates were 0.94 and 0.90 for vaccinated and non-vaccinated birds, respectively.
      The comparison for the whole period between vaccinated and non-vaccinated groups
      did not show a significant statistical difference for mortality. However, when
      mortality was compared between vaccinated and non-vaccinated turkeys for each
      month of the study, there was a statistically significant difference for the
      first month (relative risk = 0.216, confidence interval 0.069 to 0.676). In
      addition, when the severity of pox lesions between groups was compared,
      statistically significant differences were found in favour of the vaccinated
      birds (P < 0.0001). 

PMID- 24099590
TI  - Improved efficacy of acylfulvene in colon cancer cells when combined with a
      nuclear excision repair inhibitor.
AB  - The efficacy of DNA-damaging anticancer drugs is highly influenced by cellular
      DNA repair capacity, and by inhibiting the relevant DNA repair pathway, efficacy
      of alkylating agents may be increased. Therefore, combining DNA repair inhibitors
      with anticancer agents that selectively target tumor tissue should improve cancer
      treatment. The objective of this study was to test the hypothesis that
      cotreatment of cancer cells with acylfulvene (AF, alkylating agent) and UCN-01
      (DNA repair inhibitor) would improve drug efficacy and promote the persistence of
      DNA adducts. Previous data regarding the relative susceptibility of repair
      proficient versus deficient cells toward an AF analogue suggests that
      corresponding adducts are repaired by nuclear excision repair (NER), a cellular
      process that has been shown to be prevented with UCN-01. In this study, cells
      were cotreated with nontoxic levels of UCN-01 together with increasing doses of
      AF. The efficacy of AF was assessed by measuring cytotoxicity and DNA adducts. In
      addition, cells were cotreated with nontoxic levels of methoxyamine, a known base
      excision repair (BER) inhibitor, to determine if inhibiting BER also promotes
      cytotoxicity of AF. DNA-adducts were measured in a sensitive and precise manner
      by using stable isotope-labeled mass spectrometry analysis. The data obtained in
      this study demonstrate for the first time that pharmacological inhibition of the
      NER pathway of DNA repair leads to the persistence of AF-specific adducts and
      promotes AF cytotoxicity. 

PMID- 24099592
TI  - [Massive hepatic abscess in a liver transplant patient secondary to a late
      arterial graft thrombosis].

PMID- 24099593
TI  - [The safety of early laparoscopic cholecystectomy (<48 hours) for patients with
      mild gallstone pancreatitis: a systematic review of the literature and meta
      analysis].
AB  - BACKGROUND: In mild gallstone pancreatitis, cholecystectomy decreases the risk of
      recurrence. This should be performed during the initial hospitalization, but even
      when this is performed, the hospital stay can be prolonged, with an increase in
      costs and morbidity. The aim of this study is to compare the complication rate
      between patients who underwent an early cholecystectomy (<48 hours) vs. a late
      one (>48 hours). MATERIALS AND METHODS: A systematic search was performed in the
      following data bases: PubMed, EMBASE, LILACS and Scielo. Articles on patients
      with acute, mild gallstone pancreatitis who required a cholecystectomy during
      their initial hospitalization were included and compared with those undergoing a
      late cholecystectomy, in order to evaluate the complications, number of days of
      hospitalization and need for readmission. The quality of the studies and the
      risks of bias were evaluated. RESULTS: A total of 580 articles and summaries were
      identified which included 3 observational studies and a randomized clinical
      trial. A total of 636 patients who underwent a cholecystectomy during the initial
      hospitalization were included,. Ten of 207 (4.83%) in the early cholecystectomy
      group showed some type of complication, and 19 of 429 (4.42%) in the late
      cholecystectomy group, with a risk difference of -0.0016 IC 95% ([-0.04]-0.04).
      Three of the included studies should be considered of low quality and one of high
      quality. No publication bias was evidenced. CONCLUSION: No differences in
      complication rate were found between patients who underwent an early
      cholecystectomy versus a late cholecystectomy; nevertheless, further studies
      should be carried out in order to confirm these findings.

PMID- 24099594
TI  - The risk of potential thromboembolic, renal and cardiac complications of sickle
      cell trait.
AB  - Many complications of sickle cell trait have been well-established, but
      associations with additional disease states remain controversial. We conducted a
      retrospective cohort study to examine the frequency of receiving a diagnosis of
      thromboembolism, pulmonary embolism (PE), ischemic stroke, renal disease (acute,
      chronic), coronary artery disease (CAD) and congestive heart failure (CHF) in
      patients with sickle cell trait. A total of 13,964 adult African Americans
      registered in the Kaiser Permanente Northern California (KPNC) health system
      (Oakland, CA, USA), were included based on laboratory and diagnostic code data
      for the years 1995-2008: 2642 with sickle cell trait, 11,183 with normal
      hemoglobin (Hb) and 139 with sickle cell disease. Disease outcomes were obtained
      from coded diagnoses. The adjusted relative risk of PE and chronic kidney disease
      in sickle cell trait patients compared to patients with normal Hb were 1.37 [95%
      confidence interval (CI) 1.07-1.75] and 1.13 (95% CI 1.03-1.23), respectively.
      There were no other significant differences in the outcomes for sickle cell trait
      patients compared to patients with normal Hb.

PMID- 24099595
TI  - Non-Boltzmann population distributions during single-bubble sonoluminescence.
AB  - Single-bubble sonoluminescence (SBSL) spectra from aqueous sulfuric acid
      solutions containing dissolved neon show widely varying emission despite being
      similar in chemical composition. From a 65 wt % solution, emission from hydroxyl
      radicals is observed, with the rovibronic progression being well-described by a
      single temperature of 7600 K. From an 80 wt % solution, however, emission spectra
      reveal vibrationally hot sulfur monoxide (SO; Tv = 2400 K) that is also
      rotationally cold (Tr = 280 K). Further, the SO vibrational population
      distribution is best-described by a non-Boltzmann distribution. Excited neon atom
      emission observed from the 80 wt % solution gives an estimated temperature of
      only 3400 K, indicative of emission from a cool outer shell at the interfacial
      region. The neon atom excited-state population is also best-described by a non
      Boltzmann distribution. These observations are consistent with SBSL emission
      having both a spatial and temporal component, and the implications for these
      effects are discussed. 

PMID- 24099596
TI  - The impact of PRAISEDD on adherence and initiation of heart health behaviors in
      senior housing.
AB  - OBJECTIVE: Building on prior theoretical work and research, we developed a
      community-based intervention, People Reducing Risk And Improving Strength through
      Exercise, Diet, and Drug Adherence (PRAISEDD), a three-phase program which was
      implemented in 2009. The purpose of this study was to report on Phase III, the
      Inoculation Phase, of the PRAISEDD program and explore participant experiences.
      DESIGN AND SAMPLE: This was a descriptive, qualitative study focused on exploring
      participation in heart healthy PRAISEDD classes. Ten residents participated in
      the focus group, all of whom attended at least one PRAISEDD session. MEASURES:
      Qualitative data were obtained at the end of the 12 months during which Phase III
      was implemented. Descriptive data were gathered to describe the number of initial
      PRAISEDD participants and the number of new participants who came to classes.
      RESULTS: Nine codes were identified and reduced to two themes: motivators to
      participate in exercise classes; and factors that decrease willingness to
      participate. The Phase III monthly PRAISEDD inoculation classes were attended by
      10-12 residents, the majority of whom participated in Phase I of PRAISEDD.
      CONCLUSION: We were able to engage new participants in classes during Phase III,
      and qualitative findings provided important recommendations for future work.

PMID- 24099597
TI  - Biochemical and haematological changes in HIV subjects receiving winniecure
      antiretroviral drug in Nigeria.
AB  - BACKGROUND: Hematological and biochemical abnormalities are among the most common
      clinicopathological manifestations of HIV patients on ART. Consequently, the
      development and assessment of indigenous antiretroviral drugs with minimal
      abnormalities becomes a necessity. The objective of this investigation was to
      assess potential haematological and biochemical abnormalities that may be
      associated with the administration of Winniecure ART in HIV patients undergoing
      treatment in Nigeria. Fifty (50) confirmed HIV positive ART naive patients aged
      36 +/- 10 were observed for haematological and biochemical responses for 12
      weeks. Haematological responses were assessed thrice at 6 weeks interval using
      coulter Ac-T differential analyser and biochemical indicators (bilirubin,
      creatine, urea, amylase, ALT, ALP, AST, albumin) assayed spectrophotometrically.
      RESULTS: The biochemical parameters ALP (P < 0.05), ALT (P < 0.0001), AST (P <
      0.001) and amylase (P < 0.05) slightly increased at the 12th week, no significant
      change was observed in plasma creatinine and urea concentrations while albumin
      levels decreased non-significantly (P > 0.002). Haematological results showed
      consistent reduction of ESR, eosinophil, absolute and differential lymphocytes,
      granulocytes and total WBC in the test subjects throughout the assessment period.
      Conversely, haemoglobin, platelet and PCV increased significantly (P < 0.05). At
      the 12th week thrombocytopenia (10.30%) and anaemia (76%) were reduced to 2% and
      31% respectively while neutropenia (4.2 to 8%), leucopenia (26.8 to 30%) and
      lymphopenia (1 to 10%) increased. No cases of neutrophilia, lymphocytosis,
      eosinophilia and leukocytosis was observed. CONCLUSION: The drug has a reduced
      haematological abnormalities and normal kidney function was unaffected though
      there were signs of possible abnormal levels of hepatic enzymes beyond 12 weeks
      of treatment.

PMID- 24099598
TI  - Novel insights into pancreatic beta-cell glucolipotoxicity from real-time
      functional analysis of mitochondrial energy metabolism in INS-1E insulinoma
      cells.
AB  - High circulating glucose and non-esterified (free) fatty acid levels can cause
      pancreatic beta-cell failure. The molecular mechanisms of this beta-cell
      glucolipotoxicity are yet to be established conclusively. In the present paper we
      report on the involvement of mitochondrial dysfunction in fatty-acid-induced beta
      cell failure. We have used state-of-the-art extracellular flux technology to
      functionally probe mitochondrial energy metabolism in intact INS-1E insulinoma
      cells in real-time. We show that 24-h palmitate exposure at high glucose
      attenuates the glucose-sensitivity of mitochondrial respiration and lowers
      coupling efficiency of glucose-stimulated oxidative phosphorylation. These
      mitochondrial defects coincide with an increased level of ROS (reactive oxygen
      species), impaired GSIS (glucose-stimulated insulin secretion) and decreased cell
      viability. Palmitate lowers absolute glucose-stimulated respiration coupled to
      ATP synthesis, but does not affect mitochondrial proton leak. Palmitate is not
      toxic when administered at low glucose unless fatty acid beta-oxidation is
      inhibited. Palmitoleate, on the other hand, does not affect mitochondrial
      respiration, ROS levels, GSIS or cell viability. Although palmitoleate protects
      against the palmitate-induced ROS increase and cell viability loss, it does not
      protect against respiratory and insulin secretory defects. We conclude that
      mitochondrial dysfunction contributes to fatty-acid-induced GSIS impairment, and
      that glucolipotoxic cell viability and GSIS phenotypes are mechanistically
      distinct.

PMID- 24099600
TI  - [Whirlpool folliculitis: 6 cases outbreak report].

PMID- 24099599
TI  - The functional interplay of Helicobacter pylori factors with gastric epithelial
      cells induces a multi-step process in pathogenesis.
AB  - Infections with the human pathogen Helicobacter pylori (H. pylori) can lead to
      severe gastric diseases ranging from chronic gastritis and ulceration to
      neoplastic changes in the stomach. Development and progress of H. pylori
      associated disorders are determined by multifarious bacterial factors. Many of
      them interact directly with host cells or require specific receptors, while
      others enter the host cytoplasm to derail cellular functions. Several adhesins
      (e.g. BabA, SabA, AlpA/B, or OipA) establish close contact with the gastric
      epithelium as an important first step in persistent colonization. Soluble H.
      pylori factors (e.g. urease, VacA, or HtrA) have been suggested to alter cell
      survival and intercellular adhesions. Via a type IV secretion system (T4SS), H.
      pylori also translocates the effector cytotoxin-associated gene A (CagA) and
      peptidoglycan directly into the host cytoplasm, where cancer- and inflammation
      associated signal transduction pathways can be deregulated. Through these
      manifold possibilities of interaction with host cells, H. pylori interferes with
      the complex signal transduction networks in its host and mediates a multi-step
      pathogenesis. 

PMID- 24099602
TI  - A genome-wide analysis of simple sequence repeats in maize and the development of
      polymorphism markers from next-generation sequence data.
AB  - BACKGROUND: Maize (Zea mays ssp. mays L.), as the most important plant for staple
      food of several million people, animal feed and bioenergy productions, is widely
      cultivated around the world. Simple sequence repeats (SSRs) are widely used as
      molecular markers in maize genetics and breeding, but only two thousands pairs of
      SSRs have been published currently, which hardly satisfies for the increasing
      needs of geneticists and breeders. Furthermore, the increasing studies have
      revealed that SSRs also play a vital role in functional regulation and evolution.
      It is fortunate that the development of sequencing technology and bio-software
      provides the basis for characterization and development of SSRs in maize.
      RESULTS: In this study, MISA was applied to identify overall 179,681 SSRs in
      maize reference genome B73, with an average distance of 11.46 Kbp. Their
      distributions within the genome in different regions were non-random, and the
      density followed in a descending order of UTR, promotor, intron, intergenic and
      CDS. Meanwhile, 82,694 (46.02%) SSRs with unique flanking sequences were
      selected, and then applied to analyze the polymorphism of next-generation
      sequencing data from 345 maize inbred lines and data from maize reference genome
      B73. There were 58,946 SSRs with length information results in ten or more than
      ten genomes, accounting for 71.28% of SSRs with unique flanking sequences, while
      55,621 SSRs had polymorphism, with an average PIC value of 0.498. 250 pairs of
      SSR primers in different genomic regions covering all maize chromosomes were
      randomly chosen for the experimental validation, with an average PIC value of
      0.63 in 11 elite maize inbred lines. CONCLUSIONS: Our work provided insight into
      the non-random distribution spatterns and compositions of SSRs in different
      regions of maize genome, and also developed more polymorphic SSR markers using
      next-generation sequencing reads. The genome-wide SSRs polymorphism markers could
      be useful for genetic analysis and marker-assisted selection in breeding
      practice, and it was also proved to be high efficient for molecular marker
      development via next-generation sequencing reads.

PMID- 24099603
TI  - Quantitative chemical imaging and unsupervised analysis using hyperspectral
      coherent anti-Stokes Raman scattering microscopy.
AB  - In this work, we report a method to acquire and analyze hyperspectral coherent
      anti-Stokes Raman scattering (CARS) microscopy images of organic materials and
      biological samples resulting in an unbiased quantitative chemical analysis. The
      method employs singular value decomposition on the square root of the CARS
      intensity, providing an automatic determination of the components above noise,
      which are retained. Complex CARS susceptibility spectra, which are linear in the
      chemical composition, are retrieved from the CARS intensity spectra using the
      causality of the susceptibility by two methods, and their performance is
      evaluated by comparison with Raman spectra. We use non-negative matrix
      factorization applied to the imaginary part and the nonresonant real part of the
      susceptibility with an additional concentration constraint to obtain absolute
      susceptibility spectra of independently varying chemical components and their
      absolute concentration. We demonstrate the ability of the method to provide
      quantitative chemical analysis on known lipid mixtures. We then show the
      relevance of the method by imaging lipid-rich stem-cell-derived mouse adipocytes
      as well as differentiated embryonic stem cells with a low density of lipids. We
      retrieve and visualize the most significant chemical components with spectra
      given by water, lipid, and proteins segmenting the image into the cell
      surrounding, lipid droplets, cytosol, and the nucleus, and we reveal the chemical
      structure of the cells, with details visualized by the projection of the chemical
      contrast into a few relevant channels. 

PMID- 24099604
TI  - Prevalence of atrial fibrillation in China and its risk factors.
AB  - OBJECTIVE: To study the prevalence of atrial fibrillation (AF) and the relation
      with its risk factors in China. METHODS: A total of 19 363 participants (8635
      males and 10 728 females) aged ?35 years in geographically dispersed urban and
      rural regions of China were included in this cross-sectional survey. All
      participants received questionnaire, physical and blood examination.
      Echocardiography were performed for AF patients found in the survey. RESULTS: Of
      the 19 363 participants, 199 were diagnosed with AF. The estimated age
      standardized prevalence of AF was 0.78% in men and 0.76% in women. The prevalence
      of AF in participants aged <60 years was 0.41% in men and 0.43% in women, and was
      1.83% in both men and women aged ?60 years. About 19.0% of males and 30.9% of
      females with AF were diagnosed with valve disease. Age- and sex-adjusted
      multivariable logistic regression analysis revealed that myocardial infarction,
      left ventricular hypertrophy (LVH), obesity, and alcohol consumption were
      associated with a increased risk of AF(P<0.05). CONCLUSION: The age standardized
      prevalence of AF is 0.77% in the participants enrolled in the present study. The
      number of AF cases aged ?35 years is 5.26 million according to 2010 Chinese
      Census. Most risk factors for AF, identified mainly in Western countries, are
      also detected in China.

PMID- 24099601
TI  - Efficacy trial of a DNA/rAd5 HIV-1 preventive vaccine.
AB  - BACKGROUND: A safe and effective vaccine for the prevention of human
      immunodeficiency virus type 1 (HIV-1) infection is a global priority. We tested
      the efficacy of a DNA prime-recombinant adenovirus type 5 boost (DNA/rAd5)
      vaccine regimen in persons at increased risk for HIV-1 infection in the United
      States. METHODS: At 21 sites, we randomly assigned 2504 men or transgender women
      who have sex with men to receive the DNA/rAd5 vaccine (1253 participants) or
      placebo (1251 participants). We assessed HIV-1 acquisition from week 28 through
      month 24 (termed week 28+ infection), viral-load set point (mean plasma HIV-1 RNA
      level 10 to 20 weeks after diagnosis), and safety. The 6-plasmid DNA vaccine
      (expressing clade B Gag, Pol, and Nef and Env proteins from clades A, B, and C)
      was administered at weeks 0, 4, and 8. The rAd5 vector boost (expressing clade B
      Gag-Pol fusion protein and Env glycoproteins from clades A, B, and C) was
      administered at week 24. RESULTS: In April 2013, the data and safety monitoring
      board recommended halting vaccinations for lack of efficacy. The primary analysis
      showed that week 28+ infection had been diagnosed in 27 participants in the
      vaccine group and 21 in the placebo group (vaccine efficacy, -25.0%; 95%
      confidence interval, -121.2 to 29.3; P=0.44), with mean viral-load set points of
      4.46 and 4.47 HIV-1 RNA log10 copies per milliliter, respectively. Analysis of
      all infections during the study period (41 in the vaccine group and 31 in the
      placebo group) also showed lack of vaccine efficacy (P=0.28). The vaccine regimen
      had an acceptable side-effect profile. CONCLUSIONS: The DNA/rAd5 vaccine regimen
      did not reduce either the rate of HIV-1 acquisition or the viral-load set point
      in the population studied. (Funded by the National Institute of Allergy and
      Infectious Diseases; ClinicalTrials.gov number, NCT00865566.).

PMID- 24099605
TI  - Increased arterial stiffness in subjects with pre-diabetes among middle aged
      population in Beijing, China.
AB  - OBJECTIVE: To investigate the relationship between arterial stiffness and pre
      diabetes when assessed by the new glycosylated hemoglobin A1c (HbA1c) 5.7%-6.4%
      criterion or by impaired fasting glucose in middle aged Chinese. METHODS: 1122
      adults aged 55 years or younger in the health examination centers for physical
      check-ups were enrolled in the two large-sized Tertiary Comprehensive Hospitals
      in Beijing from June 2011 to June 2012 after excluding those who previously had
      been diagnosed or treated as diabetes or cardiovascular disease. Subjects with a
      diagnosis of pre-diabetes according to impaired fasting glucose (IFG) (fasting
      plasma glucose (FPG) levels at 5.6-6.9 mmol/L), HbA1c levels at 5.7%-6.4%, or
      both, were classified into four groups for observation: (1) Normoglycaemia
      (HbA1c<5.7% and FPG <5.6 mmol/L); (2) IFG alone (FPG levels at 5.6-6.9 mmol/L and
      HbA1c<5.7% ); (3) HbA1c 5.7%-6.4% alone (HbA1c levels at 5.7%-6.4% and FPG <5.6
      mmol/L); and (4) both HbA1c 5.7%-6.4% and IFG (HbA1c levels at 5.7%-6.4% and FPG
      levels at 5.6-6.9 mmol/L). All subjects were measured for weight, height, waist
      circumference, blood pressure, fasting plasma glucose, HbA1c, lipid profile and
      brachial-ankle pulse wave velocity (baPWV). RESULTS: The mean values of baPWV
      were 1282+/-8, 1311+/-10, 1398+/-30, and 1418+/-27 cm/s (Mean+/-SE) in
      Normoglycaemia, HbA1c 5.7%-6.4% alone, IFG alone and the both HbA1c 5.7%-6.4% and
      IFG groups, respectively. After adjusting for age, gender, blood pressure, BMI
      and triglyceride, baPWV was significantly higher in subjects with both HbA1c 5.7%
      6.4% and IFG compared among the subjects with Normoglycaemia (1350+/-14 vs.
      1301+/-6 cm/s, P=0.002) and HbA1c 5.7%-6.4% alone (1350+/-14 vs. 1309+/-8 cm/s,
      P=0.013). CONCLUSION: Subjects with pre-diabetes exhibited a greater arterial
      stiffness.

PMID- 24099607
TI  - N-hexane alters the maturation of oocytes and induces apoptosis in mice.
AB  - OBJECTIVE: This study was aimed to determine the effects of n-hexane on the
      maturation of mouse oocytes. METHODS: Cell culture was used to observe the
      maturation of mouse oocytes and CLSM was employed to determine their apoptosis.
      RESULTS: Germinal vesicle breakdown (GVBD) and extrusion of the first polar body
      in mouse oocytes were significantly inhibited by n-hexane. After fertilization,
      the number of eggs in the mouse was significantly reduced by n-hexane.
      Mitochondrial membrane potentials (DeltaPsim) were altered in mouse oocytes that
      were leading to apoptosis of the oocytes. CONCLUSION: N-hexane might have
      affected the maturation of oocytes, causing alteration of DeltaPsim and leading
      to apoptosis which maybe one of the most important mechanisms.

PMID- 24099606
TI  - Simulated microgravity conditions and carbon ion irradiation induce spermatogenic
      cell apoptosis and sperm DNA damage.
AB  - OBJECTIVE: To investigate the effect of simulated microgravity and carbon ion
      irradiation (CIR) on spermatogenic cell apoptosis and sperm DNA damage to the
      testis of male Swiss Webster mice, and assess the risk associated with space
      environment. METHODS: Sperm DNA damage indicated by DNA fragmentation index (DFI)
      and high DNA stainability (HDS) was measured by sperm chromatin structure assay
      (SCSA). Apoptosis of spermatogenic cells was detected by annexin V-propidium
      iodide assay. Bax (the expression levels of p53) and proliferating cell nuclear
      antigen (PCNA) were measured by immunoblotting; p53 and PCNA were located by
      immunohistology. RESULTS: HDS, DFI, apoptosis index, and the expression levels of
      p53 and Bax were detected to be significantly higher in the experimental groups
      (P<0.05) compared with those in the control group; however, the PCNA expression
      varied to a certain degree. p53- and PCNA- positive expression were detected in
      each group, mainly in relation to the spermatogonic cells and spermatocytes.
      CONCLUSION: The findings of the present study demonstrated that simulated
      microgravity and CIR can induce spermatogenic cell apoptosis and sperm DNA
      damage. Sperm DNA damage may be one of the underlying mechanisms behind male
      fertility decline under space environment. These findings may provide a
      scientific basis for protecting astronauts and space traveler's health and
      safety.

PMID- 24099608
TI  - Effects of selected metal oxide nanoparticles on multiple biomarkers in Carassius
      auratus.
AB  - OBJECTIVE: To study the biological effects of nanoscale copper oxide (nCuO), zinc
      oxide (nZnO), cerium dioxide (nCeO2) and their mixtures on Carassius auratus.
      METHODS: Juvenile fish (Carassius auratus) were exposed to aqueous suspensions of
      nCuO, nZnO, and nCeO2 (alone and in mixtures) at concentrations of 20, 40, 80,
      160, and 320 mg/L. The biomarkers-acetylcholinesterase (AChE) in brain,
      sodium/potassium-activated ATPase (Na+/K+-ATPase) in gill, and superoxide
      dismutase (SOD) and catalase (CAT) in liver-were determined after 4 days of
      exposure. Integrated biomarker response (IBR) was calculated by combining
      multiple biomarkers into a single value. RESULTS: AChE and SOD activities were
      significantly inhibited by all test metal oxide nanoparticles (NPs) at high
      concentrations (?160 mg/L) with the exception of nCeO2. Na+/K+-ATPase induction
      exhibited bell-shaped concentration-response curves. CAT activity was
      significantly inhibited at concentrations equal to or higher than 160 mg/L. The
      order of IBR values was nCeO2 ~ nZnO/nCeO2 ~ nCuO/nCeO2 < nCuO/nZnO/nCeO2 < nZnO
      < nCuO < nCuO/nZnO. The joint effect seemed to be synergistic for nCuO/nZnO
      mixtures, additive for the ternary mixture and less than additive or antagonistic
      for the binary mixtures containing nCeO2. CONCLUSION: Concentration-dependent
      changes of enzymatic activities (AChE, Na+/K+-ATPase, SOD, and CAT) were observed
      in fish exposed to nanoscale metal oxides. IBR analysis allowed good
      discrimination between the different exposures and might be a useful tool for the
      quantification of integrated negative effects induced by NPs toward fish.

PMID- 24099609
TI  - Protein expression in silica dust-induced transdifferentiated rats lung
      fibroblasts.
AB  - OBJECTIVE: To analyze the expression of different proteins in free silica-induced
      transdifferentiated rat lung fibroblasts. METHODS: Rat lung fibroblasts and
      alveolar macrophages were cultured. A transdifferentiation model of rat lung
      fibroblasts was established. Free silica was used as a stimulator for rat lung
      fibroblasts. Changes in alpha-SMA were detected by immunohistochemistry and
      Western blot, respectively. Protein of lung fibroblasts was extracted and
      analyzed by two-dimensional electrophoresis (2-DE). RESULTS: Six protein spots
      were identified by mass spectrometry, including glyceraldehyde 3-phosphate
      dehydrogenase, peroxiredoxin 5, heterogeneous nuclear ribonucleoprotein A2,
      transgelin 2, keratin K6 and vimentin. CONCLUSION: Some proteins are changed in
      free silica-induced transdifferentiated rat lung fibroblasts.

PMID- 24099610
TI  - Antimicrobial profile of lactic acid bacteria isolated from vegetables and
      indigenous fermented foods of India against clinical pathogens using
      microdilution method.

PMID- 24099611
TI  - Blood oxidant/antioxidant status in overfed aging rats: comparative effects of
      sunflower and olive-linseed mixture oil rich diets.

PMID- 24099612
TI  - Effect of cadmium on rat Leydig cell testosterone production and DNA integrity in
      vitro.

PMID- 24099613
TI  - All-transretinoic acid regulates Th1/Th2 balance in CD4+ T cells when GATA-3 is
      deficient.
AB  - The essential effect of vitamin A on immune function occurs through various
      mechanisms including direct effect on Th1-Th2 balance modulation. However, it is
      unclear whether or not vitamin A can regulate Th1-Th2 balance under a strong Th1
      polarizing condition. Therefore, the purpose of our study was to examine the
      effect of vitamin A metabolite all-trans retinoic acid (ATRA) on Th1-Th2
      differentiation in CD4+ T cells under GATA-3 deficiency, which can induce Th1
      polarizing condition. In the present study, GATA-3 deficiency T cells were
      induced by siRNA and checked by real-time quantitative PCR and western blot. GATA
      3 deficiency CD4+ T cells and normal CD4+ T were treated for 48 h with or without
      ATRA. The expression of Th1 and Th2 cytokines were detected by qPCR and ELISA.
      The results would contribute to clarify the knowledge of the role of vitamin A in
      regulating Th1-Th2 balance under some special conditions, and help to explain the
      mechanism of immune regulatory function of vitamin A. 

PMID- 24099614
TI  - Screening of genes with unique mutations of microtus.

PMID- 24099615
TI  - Molecular epidemiological analysis of group A Streptococci isolated from children
      in Chaoyang District of Beijing, 2011: emm types, virulence factor genes and
      erythromycin resistant genes.

PMID- 24099616
TI  - Authors' response.

PMID- 24099617
TI  - Spatial mapping of efficiency of GaN/InGaN nanowire array solar cells using
      scanning photocurrent microscopy.
AB  - GaN-InGaN core-shell nanowire array devices are characterized by spectrally
      resolved scanning photocurrent microscopy (SPCM). The spatially resolved external
      quantum efficiency is correlated with structure and composition inferred from
      atomic force microscope (AFM) topography, scanning transmission electron
      microscope (STEM) imaging, Raman microspectroscopy, and scanning photocurrent
      microscopy (SPCM) maps of the effective absorption edge. The experimental
      analyses are coupled with finite difference time domain simulations to provide
      mechanistic understanding of spatial variations in carrier generation and
      collection, which is essential to the development of heterogeneous novel
      architecture solar cell devices. 

PMID- 24099618
TI  - Potential applications of nanoshells in biomedical sciences.
AB  - Abstract Nanotechnology is an emerging, disruptive technology with significant
      impact and application in cancer research. Nanoshells are the one such gift by
      this technology which is a dielectric core material made up of silica covered by
      thin metals especially gold. To achieve more effective and better diagnostic
      and/or therapeutic goals, nanoshells can be conjugated to antibodies,
      oligonucleotides, fluorophores, targeting ligands, polymers, therapeutic agents,
      and radioisotope. Nanoshells (and especially gold nanoshells) show promise
      application in biomedical imaging, target therapy, gene delivery, tissue welding,
      drug delivery systems, therapeutic applications in general and cancer imaging and
      treatment in particular. They find place in the field of medicine for such
      applications because of their safety, biocompatibility, stability,
      bioavailability, optically tunable, and photoluminescent ability as well as high
      ability to attach to many therapeutic materials. In this review, we
      comprehensively discuss the potential biomedical applications of different type
      of nanoshells. This review is briefly outlined in Figure 1 .

PMID- 24099619
TI  - Berberine-induced pigment dispersion in Bufo melanostictus melanophores by
      stimulation of beta-2 adrenergic receptors.
AB  - Reduced production of melanin by decreased or the absence of melanocytes leads to
      various hypopigmentation disorders, and the development of melanogenetic agents
      for photoprotection and hypopigmentation disorders is one of the top priority
      areas of research. Hence, the present study was carried out to elucidate the
      ability of berberine, a principal active ingredient present in the roots of the
      herb Berberis vulgaris to stimulate pigment dispersion in the isolated skin
      melanophores of the toad Bufo melanostictus. In the present study, mean
      melanophore size index of the isolated skin melanophores of B. melanostictus was
      assayed after treating with various concentrations of berberine. A marked melanin
      dispersion response leading to skin darkening was observed in the isolated
      melanophores of toad in response to berberine, which was found to be mediated
      through beta-2 adrenergic receptors. The physiologically significant dose-related
      melanin dispersion effects of berberine per se were found to be completely
      abolished by propranolol, which is a specific beta-2 adrenergic receptor blocker.
      These per se melanin dispersal effects were also found to be markedly potentiated
      by isoprenaline, which is a specific beta-adrenoceptor agonist. The results
      indicate that berberine causes a tremendous, dose-dependent, physiologically
      significant pigment dispersing in the isolated skin melanophores of B.
      melanostictus.

PMID- 24099620
TI  - Microwave-assisted carbohydrohalogenation of first-row transition-metal oxides (M
      = V, Cr, Mn, Fe, Co, Ni, Cu) with the formation of element halides.
AB  - The anhydrous forms of first-row transition-metal chlorides and bromides ranging
      from vanadium to copper were synthesized in a one-step reaction using the
      relatively inexpensive element oxides, carbon sources, and halogen halides as
      starting materials. The reactions were carried out in a microwave oven to give
      quantitative yields within short reaction times. 

PMID- 24099621
TI  - The relationship between maternal methadone dose at delivery and neonatal
      outcome: methodological and design considerations.
AB  - Compared to untreated opioid dependence, methadone maintenance treatment of
      opioid-dependent pregnant women has been found to be associated with better
      maternal and neonatal outcomes. Secondary analysis of data from 73 maternal and
      neonatal participants in the MOTHER study (H. E. Jones et al., New England
      Journal of Medicine, 2010) found no relationship between maternal methadone dose
      at delivery and any of 9 neonatal outcomes--peak neonatal abstinence syndrome
      (NAS) score, total amount of morphine needed to treat NAS, duration of neonatal
      hospital stay, duration of treatment for NAS, estimated gestational age at
      delivery, Apgar score at 5 min, and neonatal head circumference, length, and
      weight at birth. These results are consistent with a recent systematic review and
      meta-analysis (B. J. Cleary et al., Addiction, 2010) and extend findings to
      outcomes other than NAS. Methodological and design issues that might have
      adversely impacted the ability of researchers to establish the existence or non
      existence of these relationships are considered.

PMID- 24099622
TI  - Maternal methadone dose during pregnancy and infant clinical outcome: response to
      O'Grady et al.
AB  - We agree with O'Grady et al. (2013) that the relationships between maternal
      methadone dose during pregnancy and neonatal outcomes deserve serious attention.
      However, we would also argue that a broader range of infant health and
      neurobehavioral outcomes need to be considered, not only in the short but also
      the longer term. 

PMID- 24099623
TI  - Nonstandard peptide expression under the genetic code consisting of reprogrammed
      dual sense codons.
AB  - We here demonstrate a translation system that is governed by a reprogrammed
      genetic code consisting of "dual sense codons." A dual sense codon assigns two
      distinct amino acids for initiation and elongation. Because multiple dual sense
      codons independently function without cross-readings, this system enables the
      expansion of the repertoire of initiators as well as elongators that can be used
      simultaneously. 

PMID- 24099624
TI  - Load-sensitive dynamic workflow re-orchestration and optimisation for faster
      patient healthcare.
AB  - Hospital waiting times are considerably long, with no signs of reducing any-time
      soon. A number of factors including population growth, the ageing population and
      a lack of new infrastructure are expected to further exacerbate waiting times in
      the near future. In this work, we show how healthcare services can be modelled as
      queueing nodes, together with healthcare service workflows, such that these
      workflows can be optimised during execution in order to reduce patient waiting
      times. Services such as X-ray, computer tomography, and magnetic resonance
      imaging often form queues, thus, by taking into account the waiting times of each
      service, the workflow can be re-orchestrated and optimised. Experimental results
      indicate average waiting time reductions are achievable by optimising workflows
      using dynamic re-orchestration. 

PMID- 24099625
TI  - Optimal bone density distributions: numerical analysis of the osteocyte spatial
      influence in bone remodeling.
AB  - In this paper a control and optimization procedure for bone remodeling
      simulations was adopted to study the effect of the osteocyte influence range on
      the predicted density distribution. In order to reach this goal, the osteocyte
      network regulating bone remodeling process in a 2-D bone sample was numerically
      simulated. The assumed proportional-integral-derivative (PID) bone remodeling
      rule was related to the error signal between the strain energy density and a
      selected target. Furthermore the control parameters and the target were optimally
      determined minimizing a suitable cost index: the goal was to minimize the final
      mass and the energy thus maximizing the stiffness. The continuum model results
      show that the developed and adapted trabecular structure was consistent with the
      applied loads and only depended on the external forces, the value of the cost
      index, the maximum attainable elastic modulus value (hence, the maximum density
      value) and the value of the energy target. The remodeling phenomenon determined
      the number and thickness of the trabeculae which are formed from a uniform
      distribution of mass density in the considered domain; this number and these
      thicknesses are controlled by the values assigned to the parameters of the model.
      In particular, the osteocyte decay distance (D) of the influence range affected
      the trabecular patterns formation, showing an important effect in the adaptive
      capacity of the optimization numerical model. 

PMID- 24099626
TI  - Intraarterial therapies for primary liver cancer: state of the art.
AB  - Image-guided intraarterial therapies play an important role in the treatment of
      patients with hepatic malignancies. These therapies provide the dual benefit of
      reduced systemic toxicity and effective local tumor control. As a result,
      procedures such as transarterial chemoembolization have been included in the
      official treatment guidelines for hepatocellular carcinoma (HCC) and are fully
      accepted for the treatment of patients with intermediate stage disease. In this
      review, we will describe the scientific rationale for intraarterial therapies and
      discuss the available clinical evidence for primary liver cancer. Finally, we
      will touch on the current trends consisting of combining intraarterial approaches
      with systemically administered targeted agents. 

PMID- 24099627
TI  - The performance of approximations of farm contiguity compared to contiguity
      defined using detailed geographical information in two sample areas in Scotland:
      implications for foot-and-mouth disease modelling.
AB  - BACKGROUND: When modelling infectious diseases, accurately capturing the pattern
      of dissemination through space is key to providing optimal recommendations for
      control. Mathematical models of disease spread in livestock, such as for foot-and
      mouth disease (FMD), have done this by incorporating a transmission kernel which
      describes the decay in transmission rate with increasing Euclidean distance from
      an infected premises (IP). However, this assumes a homogenous landscape, and is
      based on the distance between point locations of farms. Indeed, underlying the
      spatial pattern of spread are the contact networks involved in transmission.
      Accordingly, area-weighted tessellation around farm point locations has been used
      to approximate field-contiguity and simulate the effect of contiguous premises
      (CP) culling for FMD. Here, geographic data were used to determine contiguity
      based on distance between premises' fields and presence of landscape features for
      two sample areas in Scotland. Sensitivity, positive predictive value, and the
      True Skill Statistic (TSS) were calculated to determine how point distance
      measures and area-weighted tessellation compared to the 'gold standard' of the
      map-based measures in identifying CPs. In addition, the mean degree and density
      of the different contact networks were calculated. RESULTS: Utilising point
      distances <1 km and <5 km as a measure for contiguity resulted in poor
      discrimination between map-based CPs/non-CPs (TSS 0.279-0.344 and 0.385-0.400,
      respectively). Point distance <1 km missed a high proportion of map-based CPs; <5
      km point distance picked up a high proportion of map-based non-CPs as CPs. Area
      weighted tessellation performed best, with reasonable discrimination between map
      based CPs/non-CPs (TSS 0.617-0.737) and comparable mean degree and density.
      Landscape features altered network properties considerably when taken into
      account. CONCLUSION: The farming landscape is not homogeneous. Basing contiguity
      on geographic locations of field boundaries and including landscape features
      known to affect transmission into FMD models are likely to improve individual
      farm-level accuracy of spatial predictions in the event of future outbreaks. If a
      substantial proportion of FMD transmission events are by contiguous spread, and
      CPs should be assigned an elevated relative transmission rate, the shape of the
      kernel could be significantly altered since ability to discriminate between map
      based CPs and non-CPs is different over different Euclidean distances.

PMID- 24099628
TI  - Distinctive mutation spectrum of the HBB gene in an urban eastern Indian
      population.
AB  - ABSTRACT Hemoglobinopathies such as beta-thalassemia (beta-thal) and sickle cell
      anemia (or Hb S [beta6(A3)Glu->Val]) impose a major health burden in the Indian
      population. To determine the frequencies of the HBB gene mutations in eastern
      Indian populations and to compare with the available data, a comprehensive
      molecular analysis of the HBB gene was done in the normal Odisha State
      population. Using polymerase chain reaction (PCR), restriction fragment length
      polymorphism (RFLP), amplification refractory mutation system (ARMS) and DNA
      sequencing techniques, beta-thal and sickle cell anemia mutations were
      characterized in 267 healthy individuals. Entire HBB gene sequencing showed 63
      different mutations including 11 new ones. The predominant mutation HBB: c.9T > C
      was observed at a high frequency (19.57%) in the normal population. In the urban
      population of Odisha State, India, carrier frequency of hemoglobinopathies was
      found to be 18.48%, and for beta-thal, the carrier rate was 14.13%, which is very
      high indeed. In the absence of a complete cure by any expensive treatment and
      drug administration, this information would be helpful for planning a population
      screening program and establishing prenatal diagnosis of beta-thal in order to
      reduce the burden of such a genetic disease.

PMID- 24099629
TI  - Dispersing carbon-based nanomaterials in aqueous phase by graphene oxides.
AB  - Graphene oxides (GO) can be considered as polyelectrolytes with surfactant-like
      characteristics. On one hand, due to the electrical repulsion between the
      negatively charged ionized edges, GO exhibits great water solubility; on the
      other hand, its hydrophobic central plane retains the potential of strong pi-pi
      interaction with other conjugated sp(2) network structures. Therefore, it is
      expected that GO can serve as an excellent dispersing agent for dispersion of
      various carbon-based nanomaterials in aqueous phase. Here we report a systematic
      study of dispersing various carbon-based nanomaterials, including SWNTs, C60, and
      graphene, by aqueous GO. The GO-dispersed all-carbon nanocomposites are
      characterized using various spectroscopic methods and electron microscopies, and
      their stabilities are tested. Compared to other dispersing agents, the GO
      concentration is much lower than the concentrations of other dispersing agents
      used when similar contents of carbon-based nanomaterials are dispersed. Involving
      only simple ultrasonication and centrifugation processes, GO dispersion thus
      offers an easy manipulation for large-scale solution-dispersed all-carbon
      nanocomposites. 

PMID- 24099630
TI  - Changes in cortical thickness across the lifespan in major depressive disorder.
AB  - Neurobiological mechanisms underlying the development of major depressive
      disorder (MDD) may differ depending on age-of-onset. Our aim was to compare
      patients who differ in age-of-onset, while controlling for illness duration, and
      number of depressive episodes. By directly comparing early-(EOD) and late-onset
      (LOD) patients, we examined whether age-of-onset is associated with changes in
      the extent or spatial pattern of cortical thickness. Cross-sectional comparison
      of cortical thickness in EOD vs. LOD. Age-of-onset was determined based on self
      report, with EOD defined as onset prior to age 25. Reduced cortical thickness in
      the dorsal-lateral prefrontal cortex (DLPFC), pre- and postcentral gyrus, and the
      lingual gyrus were found in EOD compared to healthy controls (p<0.001). In linear
      regression models controlling for number of episodes, illness duration, severity,
      and sex, differences (at p<0.001) were found between EOD and LOD in the bilateral
      posterior cingulate, parahippocampal gyri, right precuneus, lingual, and fusiform
      gyri, but not the DLPFC. EOD is associated with greater disturbances in cortical
      thickness than LOD, even when duration of illness and other factors are
      controlled. These results provide novel insights on how development of depression
      is differentiated by age. 

PMID- 24099631
TI  - Vietnam veterans: getting old, getting sick--is this service related?

PMID- 24099632
TI  - Partially-desulfated heparin improves survival in Pseudomonas pneumonia by
      enhancing bacterial clearance and ameliorating lung injury.
AB  - Nosocomial pneumonia (NP, or hospital-acquired pneumonia) is associated with
      infections originating from hospital-borne pathogens. Persistent microbial
      presence and acute lung injury are common features of these infections,
      contributing to the high mortality rates and excessive financial burden for these
      patients. Pseudomonas aeruginosa (PA), a gram-negative opportunistic pathogen, is
      one of the prominent pathogens associated with NP. PA pneumonia is characterized
      by excessive secretion of inflammatory cytokines, neutrophil infiltration, and
      subsequent lung damage. The persistent presence of PA along with overwhelming
      inflammatory response is suggestive of impairment in innate immunity. High
      mobility group box 1 (HMGB1), a recently discovered potent pro-inflammatory
      cytokine, plays an important role in PA lung infections by compromising innate
      immunity via impairing phagocyte function through toll-like receptors (TLR) TLR2
      and TLR4. ODSH (2-O, 3-O-desulfated heparin), a heparin derivative with
      significant anti-inflammatory properties but minimal anti-coagulatory effects,
      has been shown to reduce neutrophilic lung injury in the absence of active
      microbial infections. This study examined the effects of ODSH on PA pneumonia.
      This study demonstrates that ODSH not only reduced PA-induced lung injury, but
      also significantly increased bacterial clearance. The ameliorated lung injury,
      together with the increased bacterial clearance, resulted in marked improvement
      in the survival of these animals. The resulting attenuation in lung injury and
      improvement in bacterial clearance were associated with decreased levels of
      airway HMGB1. Furthermore, binding of HMGB1 to its receptors TLR2 and TLR4 was
      blunted in the presence of ODSH. These data suggest that ODSH provides a
      potential novel approach in the adjunctive treatment of PA pneumonia.

PMID- 24099633
TI  - Differential effects of eugenol against hepatic inflammation and overall damage
      induced by ischemia/re-perfusion injury.
AB  - Liver injuries, liver tumor resection, and liver transplantation are known to be
      responsible for ischemia/reperfusion (I/R) injury that, in turn, gives rise to
      liver damage. This study was undertaken to investigate the possible protective
      effect of eugenol against the damage induced by I/R in rat livers as well as to
      explore possible mechanisms of action. Male rats were divided into four groups:
      sham-operated, I/R only, and two groups that received 10 or 100 mg eugenol/kg/day
      (Eug10 and Eug100, respectively) for 15 days by gavage and were then subjected to
      I/R, i.e. an ischemia induced for 45 min followed by re-perfusion for 6 h. The
      rats were euthanized and liver tissues and blood collected for examination. The
      results showed that I/R induced massive hepatic structural and functional damage.
      Eug10-treated rats had improvement in both liver function and structure, and
      inhibition of I/R-induced increases in serum myeloperoxidase (MPO), tumor
      necrosis factor (TNF)-alpha, as well as hepatic nuclear factor-kappaB (NF-kappaB)
      p65 and caspase-3 expression. Eug10 treatment also inhibited the degree of loss
      in reduced glutathione (GSH) and of rise in malondialdehyde (MDA) levels in liver
      tissues induced by I/R. In contrast, augmentation of liver damage induced by I/R
      was noted in Eug100-treated rats, with these hosts displaying significant
      increases in oxidant, inflammatory, and apoptotic markers relative to levels seen
      in I/R-only rats. The results of the present study provide the first evidence
      that a low dose of eugenol may protect the liver against I/R injury in part by
      decreasing levels of lipid peroxidation, down-regulating inflammatory mediators,
      and inhibiting apoptosis, and that a larger dose amplifies the liver injury via
      oxidant and inflammatory effects.

PMID- 24099634
TI  - Ubiquitin ligase A20 regulates p53 protein in human colon epithelial cells.
AB  - BACKGROUND: Intestinal polyps may further develop into colon cancer; the
      pathogenesis is not clear. The p53 gene is an important anti-cancer gene in the
      body, which is suppressed in cancer. The ubiquitin E3 ligase A20 (A20) plays a
      role in regulating the activities of epithelial cells. This study was designed to
      investigate the role of the colon polyp epithelium-derived A20 in the
      pathogenesis of colon cancer. RESULTS: Eighty-eight colon cancer patients and 136
      colon polyp patients were recruited into this study. Human colon cancer tissue,
      the epithelium of adenomas polyp and hyperplastic polyp showed high levels of
      A20, which had a positive correlation with the cancerous tendency of colon
      polyps. The levels of A20 were much higher in the adenomas and hyperplastic
      polyps than that in the inflammatory polyps; the latter showed less cancerous
      tendency. A20 bound p53 to form complexes in colon cancer tissue and colon
      polyps. Over expression of A20 suppresses P53 protein levels in the HEK293 cells.
      CONCLUSIONS: A20 may play an important role in the cancerous tendency of colon
      polyposis.

PMID- 24099635
TI  - Barriers to colorectal cancer screening among women in rural central
      Pennsylvania: primary care physicians' perspective.
AB  - INTRODUCTION: Colorectal cancer (CRC) is the third leading cause of death among
      women in the USA. Rural populations have lower rates of CRC screening than their
      urban counterparts, and rural women have lower screening rates compared with
      rural men. The purpose of this qualitative study was to identify (1) beliefs of
      primary care physicians (PCPs) about CRC screening in rural communities, (2)
      factors that may cause gender disparities in CRC screening in rural areas, and
      (3) solutions to overcome those barriers. METHODS: Semi-structured interviews
      were conducted with 17 PCPs practicing in rural central Pennsylvania. PCPs were
      asked about their CRC screening practices for women, availability of CRC
      screening services, reminder systems for CRC screening, and barriers to screening
      specific to their rural communities and to gender. Thematic analysis was used to
      identify major themes. RESULTS: All 17 PCPs endorsed the importance of CRC
      screening, but believed that there are barriers to CRC screening specific to
      women and to rural location. All PCPs identified colonoscopy as their screening
      method of choice, and generally reported that access to colonoscopy services in
      their rural areas was not a significant barrier. Barriers to CRC screening for
      women in rural communities were related to (1) PCPs' CRC screening practices, (2)
      gender-specific barriers to CRC screening, (3) patient-related barriers, (4)
      community-related barriers, and (5) physician practice-related barriers.
      Physicians overwhelmingly identified patient education as necessary for improving
      CRC screening in their rural communities, but believed that education would have
      to come from a source outside the rural primary care office due to lack of
      resources, personnel, and time. CONCLUSION: Overall, the PCPs in this study were
      motivated to identify ways to improve their ability to engage more eligible
      patients in CRC screening. These findings suggest several interventions to
      potentially improve CRC screening for women in rural areas, including encouraging
      use of other effective CRC screening modalities (eg fecal occult blood testing)
      when colonoscopy is not possible, systems-based reminders that leverage
      electronic resources and are not visit-dependent, and public health education
      campaigns aimed specifically at women in rural communities.

PMID- 24099636
TI  - Complexes assembled from TMV-derived spherical particles and entire virions of
      heterogeneous nature.
AB  - Previously, we described some structural features of spherical particles (SPs)
      generated by thermal remodelling of the tobacco mosaic virus. The SPs represent a
      universal platform that could bind various proteins. Here, we report that entire
      isometric virions of heterogeneous nature bind non-specifically to the SPs.
      Formaldehyde (FA) was used for covalent binding of a virus to the SPs surface for
      stabilizing the SP-virus complexes. Transmission and high resolution scanning
      electron microscopy showed that the SPs surface was covered with virus particles.
      The architecture of SP-virion complexes was examined by immunologic methods. Mean
      diameters of SPs and SP-human enterovirus C and SP-cauliflower mosaic virus
      (CaMV) compositions were determined by nanoparticle tracking analysis (NTA) in
      liquid. Significantly, neither free SPs nor individual virions were detected by
      NTA in either FA-crosslinked or FA-untreated compositions. Entirely, all virions
      were bound to the SPs surface and the SP sites within the SP-CaMV complexes were
      inaccessible for anti-SP antibodies. Likewise, the SPs immunogenicity within the
      FA-treated SPs-CaMV compositions was negligible. Apparently, the SP antigenic
      sites were hidden and masked by virions within the compositions. Previously, we
      reported that the SPs exhibited adjuvant activity when foreign proteins/epitopes
      were mixed with or crosslinked to SPs. We found that immunogenicity of entire
      CaMV crosslinked to SP was rather low which could be due to the above-mentioned
      masking of the SPs booster. Contrastingly, immunogenicity of the FA-untreated
      compositions increased significantly, presumably, due to partial release of
      virions and unmasking of some SPs-buster sites after animals immunization. 

PMID- 24099638
TI  - Signal amplification in enzyme-based amperometric biosensors.
AB  - A unique mode of current amplification was investigated in reagentless biosensors
      based on the clinically significant enzymes including alcohol dehydrogenase,
      glucose 6-phosphate dehydrogenase, glycerol 3-phosphate dehydrogenase, and
      glucose oxidase. The biosensors were designed by sandwiching the enzyme-polymer
      film between an electrode and Nafion film. In particular, each enzyme and its
      cofactor were covalently attached to the chains of polysaccharide chitosan and
      mixed with carbon nanotubes on the electrode surface. The coating of such
      biosensors with Nafion resulted in the current increase by up to 1000%, depending
      on the enzyme. The results were analyzed considering the interplay between the
      enzyme activity-pH profiles and the Nafion-induced pH increase in the underlying
      chitosan film. The data were collected by using the rapid (<5 min) amperometric
      enzyme assays and pH-sensitive iridium oxide films. The increase in the biosensor
      current was attributed to the pH-driven increase in the enzyme activity inside
      the two-film interface. Such signal amplification should also be feasible in
      other biosensors based on the polyelectrolytes and sandwiched enzymes providing
      that a proper match is made between the enzyme activity-pH profiles and the pH of
      buffer solutions. 

PMID- 24099637
TI  - Effects of dopaminergic modulation on automatic semantic priming: a double-blind
      study.
AB  - BACKGROUND: Enhanced automatic spreading of activation in the semantic network
      has been suggested to underlie formal thought disorder in patients with
      schizophrenia, but it is not clear how this relates to the dopaminergic
      dysfunction implicated in the disorder. Previous studies on dopaminergic
      modulation of priming in healthy volunteers have focused on controlled rather
      than automatic processes. The present study aimed to examine the effects of both
      a dopaminergic agonist and a dopaminergic antagonist on semantic priming while
      minimizing the contribution of controlled processes. METHODS: We investigated the
      effects of levodopa (L-Dopa; 100 mg), haloperidol (2 mg) and placebo on priming
      in healthy participants within a randomized, double-blind, crossover design. We
      used a pronunciation priming task with word triplets; the middle word was an
      ambiguous word, whereas the first word of the triplet served to provide either a
      congruent, incongruent or unbiased context for the target word. Two stimulus
      onset asynchronies (SOA) were used: 150 ms and 750 ms. RESULTS: The study
      involved 34 participants. At an SOA of 150 ms, L-Dopa accelerated responses to
      incongruent targets and subordinate targets of ambiguous words, whereas
      haloperidol was associated with faster responses in congruent contexts and
      dominant targets. At an SOA of 750 ms, haloperidol accelerated responses to
      subordinate targets. LIMITATIONS: Modulations in the relative magnitude of
      priming according to substance and condition rather than absolute priming were
      assessed. CONCLUSION: Effects of L-Dopa on automatic priming processes appear to
      be different than those on controlled processes. Our results are consistent with
      those of studies on semantic priming and the effects on antipsychotics in
      patients with schizophrenia.

PMID- 24099639
TI  - Preparation and evaluation of folate-modified lipid nanocapsules for quercetin
      delivery.
AB  - Folate-modified lipid nanocapsule encapsulated quercetin (QT-FALNC) was prepared
      with phase inversion method. The formulation was optimized by simplex lattice
      design with encapsulation efficiency and drug loading as index. The encapsulation
      efficiency and drug loading of the optimal formulation were 96.01% and 2.98%,
      respectively. The drug concentration in QT-FALNC suspension was 4.29 mg/mL. Under
      transmission electron microscopy, the QT-FALNC showed spherical shape with a
      narrow size distribution. The particle size and zeta potential of QT-FALNC were
      36.2 nm and -4.76 mV, respectively. The pharmacokinetics study in rats showed
      that the mean retention time (MRT0-infinity) of the non-targeting lipid
      nanocapsules (LNC) loading quercetin (QT-LNC) and the targeting QT-FALNC was
      12.981 h and 15.086 h, respectively, indicating that LNC could prolong the effect
      of QT in vivo. The in vitro anti-proliferative activity and cellar uptake of QT
      FALNC were studied on Hela and MCF-7/MDR cells. The results showed that both QT
      LNC and QT-FALNC displayed a stronger cell-killing effect than free QT. The in
      vivo anti-tumor study indicated that both QT-LNC and QT-FALNC showed the
      significant inhibition effect on tumor growth in H22 tumor-bearing mice compared
      with the control. It can be concluded that lipid nanocapsule is a potential
      carrier for improving solubility and biological activity of QT.

PMID- 24099640
TI  - Traceless directing strategy: efficient synthesis of N-alkyl indoles via redox
      neutral C-H activation.
AB  - A general protocol for the synthesis of N-alkyl indoles has been developed via a
      redox neutral C-H activation strategy using a traceless nitroso directing group.
      A broad scope of substituted N-alkyl indoles has been prepared in good to
      excellent yields using a very simple Rh catalyst system in the absence of an
      external oxidant or any other additive. Good to excellent regioselectivity has
      been achieved for asymmetrically disubstituted acetylenes. 

PMID- 24099641
TI  - MRI-guided biopsy and fine needle aspiration biopsy (FNAB) in the diagnosis of
      musculoskeletal lesions.
AB  - OBJECTIVES: The purpose of this study was to evaluate the diagnostic performance
      of magnetic resonance imaging (MRI) guided musculoskeletal biopsy and the value
      of fine needle aspiration biopsy (FNAB) when combined with histologic biopsy.
      MATERIALS AND METHODS: A total of 172 biopsies were performed under MRI guidance,
      170 were histologic biopsies. In 112 cases, a fine needle aspiration biopsy was
      also performed. In two cases, a stand-alone FNAB was performed. The diagnostic
      performance was evaluated retrospectively by comparing the histopathologic and
      cytologic diagnosis with the current or final diagnosis after at least one year
      of clinical and imaging follow-up. A 0.23 T open MRI scanner with an
      interventional stereotactic guidance system was used. RESULTS: The overall
      diagnostic accuracy of MRI guided biopsy was 0.95, sensitivity 0.91, specificity
      0.98, positive predictive value (ppv) 0.97 and negative predictive value (npv)
      0.93. The diagnostic accuracy of trephine biopsy alone was 0.93, sensitivity
      0.89, specificity 0.98, ppv 0.97 and npv 0.91 and accuracy for FNAB alone was
      0.85, sensitivity 0.80, specificity 0.90, ppv 0.89 and npv 0.82. CONCLUSIONS: MRI
      guidance is a feasible and accurate tool in percutaneous musculoskeletal
      biopsies. Fine needle biopsy is a useful low-cost supplement to histologic
      biopsy.

PMID- 24099642
TI  - Comparison of the diagnostic performances of diffusion parameters in diffusion
      weighted imaging and diffusion tensor imaging of breast lesions.
AB  - PURPOSE: To evaluate the diagnostic efficiency of the diffusion parameters
      measured by conventional diffusion-weighted imaging (DWI) and diffusion tensor
      imaging (DTI) for discrimination of malignant breast lesions from benign lesions
      and the normal breast. MATERIALS AND METHODS: The study included 52 women with 55
      breast lesions (30 malignant, 25 benign). DTI and DWI were performed
      complementary to dynamic contrast MRI at 3T. Apparent diffusion coefficient (ADC)
      of DWI, mean diffusivity (MD) and fractional anisotropy (FA) values of DTI were
      measured for lesions and contralateral breast parenchyma in each patient. We used
      b factors of 0, 50, 850, 1000 and 1500 s/mm(2) for DWI and b 0 and 1000 s/mm(2)
      for DTI. ADC, MD and FA values were compared between malignant and benign
      lesions, and the normal parenchyma by univariate and multivariate analyses.
      RESULTS: Diffusion parameters showed no difference according to menopausal status
      in the normal breast. ADC and MD values of the malignant lesions were
      significantly lower than benign lesions and normal parenchyma (p=0.001). The FA
      showed no statistical significance. With the cut-off values of <= 1.23 * 10(
      3)mm(2)/s (b 0-1000 s/mm(2)) and <= 1.12 * 10(-3)mm(2)/s (b 0-1500 s/mm(2)), ADC
      showed 92.85% and 96.15% sensitivity; 72.22% and 73.52% PPV, respectively. With a
      cut-off value of <= 1.27 * 10(-3)mm(2)/s (b 1000 s/mm(2)), MD was 100% sensitive
      with a PPV of 65.90%. Comparing the diagnostic performance of the parameters in
      DTI with DWI, we obtained similar efficiency of ADC with b values of 0,1000 and
      0,1500 s/mm(2) and MD with a b value of 0, 1000 s/mm(2) (AUC = 0.82 +/- 0.07).
      CONCLUSION: ADC of DWI and MD of DTI values provide significant discriminative
      factors for benign and malignant breast lesions. FA measurement was not
      discriminative. Supported with clinical and dynamic contrast MRI findings, DWI
      and DTI findings provide significant contribution to the final radiologic
      decision.

PMID- 24099644
TI  - Effect of different coping designs on all-ceramic crown stress distribution: a
      finite element analysis.
AB  - OBJECTIVE: To investigate the effect of differential coping designs on the stress
      distributions of an all-ceramic crown on, the upper central incisor under varying
      loads. METHODS: 3D finite element models with three differential coping designs
      of an all-ceramic crown on, the upper central incisor were constructed using CAD
      (computer aided design) software. The coping, designs included: CC (conventional
      coping), MCL (modified coping without veneer coverage in lingual, surface) and
      MCM (modified coping without veneer coverage in lingual margin). Loading that,
      simulated the maximum bite force (200 N) was applied to the crown at differential
      locations (incisal, edge, lingual fossa and lingual margin). The first principal
      stress values for the full crown were, calculated and expressed as stress
      intensity in MPa. RESULTS: The simulations showed the stress distribution
      tendencies of the all-ceramic crown with, differential coping materials were
      similar. The stress concentration was found in the cervical region, coping/veneer
      layer interface and the loading area for both the coping layer and the veneer
      layer. Maximal stress value was observed in the loading area. Stress values
      varied for the three types of, coping designs; however, compared with CC and MCM,
      MCL exhibited the lowest stress values. SIGNIFICANCE: Modified coping without
      veneer coverage in the lingual side (MCL) proved promising in, preventing all
      ceramic crown failures that originate from veneering porcelain, especially under,
      abnormal occlusal force.

PMID- 24099643
TI  - Influence of lean and fat mass on bone mineral density and on urinary stone risk
      factors in healthy women.
AB  - BACKGROUND: The role of body composition (lean mass and fat mass) on urine
      chemistries and bone quality is still debated. Our aim was therefore to determine
      the effect of lean mass and fat mass on urine composition and bone mineral
      density (BMD) in a cohort of healthy females. MATERIALS AND METHODS: 78 female
      volunteers (mean age 46 +/- 6 years) were enrolled at the Stone Clinic of Parma
      University Hospital and subdued to 24-hour urine collection for lithogenic risk
      profile, DEXA, and 3-day dietary diary. We defined two mathematical indexes
      derived from body composition measurement (index of lean mass-ILM, and index of
      fat mass-IFM) and the cohort was split using the median value of each index,
      obtaining groups differing only for lean or fat mass. We then analyzed
      differences in urine composition, dietary intakes and BMD. RESULTS: The women
      with high values of ILM had significantly higher excretion of creatinine (991 +/-
      194 vs 1138 +/- 191 mg/day, p = 0.001), potassium (47 +/- 13 vs 60 +/- 18
      mEq/day, p < 0.001), phosphorus (520 +/- 174 vs 665 +/- 186 mg/day, p < 0.001),
      magnesium (66 +/- 20 vs 85 +/- 26 mg/day, p < 0.001), citrate (620 +/- 178 vs 807
      +/- 323 mg/day, p = 0.002) and oxalate (21 +/- 7 vs 27 +/- 11 mg/day, p = 0.015)
      and a significantly better BMD values in limbs than other women with low values
      of ILM. The women with high values of IFM had similar urine composition to other
      women with low values of IFM, but significantly better BMD in axial sites. No
      differences in dietary habits were found in both analyses. CONCLUSIONS: Lean mass
      seems to significantly influence urine composition both in terms of lithogenesis
      promoters and inhibitors, while fat mass does not. Lean mass influences bone
      quality only in limb skeleton, while fat mass influences bone quality only in
      axial sites.

PMID- 24099645
TI  - Self-assembled peptide beads used as a template for ordered gold nanoparticle
      superstructures.
AB  - Using peptide-based materials to tailor self-assembled, nano-scaled hybrid
      materials with potentially high biocompatibility/biodegradability is gaining
      importance in developing a broad range of new applications, in areas such as
      diagnostics and medicine. Here, we investigated how the self-assembly ability of
      amphiphilic peptides can be used to create organized inorganic materials, i.e.
      gold nanoparticles. A bead-forming, purely peptidic amphiphile Ac-[K(Ac)]3-[W-l]3
      W-NH2, containing acetylated (Ac) l-lysine (K), l-tryptophan (W) and d-leucine
      (l), was C-terminally modified with a l-cysteine (C) and linked to gold
      nanoparticles. Subsequent peptide-driven self-assembly of the peptide-coated gold
      nanoparticles with increasing water content led to controlled aggregation of the
      gold-core micelles, forming composite peptide-gold superstructures. The
      individual gold nanoparticles did not agglomerate but were separated from each
      other by a peptide film within the composite material, as revealed by electron
      microscopy studies. Structural investigation on 2D template-stripped gold
      demonstrated the ability of the peptides to form self-assembled monolayers.
      Structural elements of beta-turns and weak hydrogen bonding of the hydrophobic
      moiety of the peptide were evident, thereby suggesting that the secondary
      structure remains intact. 

PMID- 24099646
TI  - Anticancer activity of liposomal bergamot essential oil (BEO) on human
      neuroblastoma cells.
AB  - Citrus extracts, particularly bergamot essential oil (BEO) and its fractions,
      have been found to exhibit anticancer efficacy. However, the poor water
      solubility, low stability and limited bioavailability have prevented the use of
      BEO in cancer therapy. To overcome such drawbacks, we formulated BEO liposomes
      that improved the water solubility of the phytocomponents and increased their
      anticancer activity in vitro against human SH-SY5Y neuroblastoma cells. The
      results warrant further investigation of BEO liposomes for in vivo applications. 

PMID- 24099647
TI  - Seeing is believing? A mixed-methods study exploring the quality and perceived
      trustworthiness of online information about chronic conditions aimed at children
      and young people.
AB  - The numbers of children and young people with chronic conditions are increasing.
      While their information needs may vary, providing health care information can
      have considerable benefits, including better emotional health, less distress
      during treatments, and greater satisfaction with medical care. The Internet is
      increasingly being used to communicate health-related information to children
      about a range of chronic conditions. However, the quality of such websites is
      underexplored. Thus, the objectives of this study were to evaluate the
      reliability and quality of online information for children about chronic
      conditions using a standardized evaluation tool, and to explore children's and
      young people's perceptions of quality and trustworthiness regarding online health
      information. The study consisted of two phases. In Phase 1, websites about common
      pediatric chronic conditions aimed at children and containing treatment or
      management options were identified and the quality assessment tool DISCERN was
      completed. Test-retest and interrater reliability were calculated. In Phase 2,
      two focus groups with laptop computers were conducted with children and young
      people with a chronic condition to explore their perceptions of trustworthiness
      of online health information. In Phase 1, 165 websites were identified and 100
      met the criteria and were assessed. The mean DISCERN score of all sites was 48.16
      out of 75 (SD = 7.97, range 28-71, min 15 to max 75). Quality scores varied
      widely across the sample. The internal consistency and interrater reliability
      scores were both lower than previously reported in studies using the DISCERN to
      assess information for adults. In Phase 2, two focus groups with a total of six
      participants aged 11-23 years revealed a relative lack of concern about the
      quality and trustworthiness of online health information. Older participants
      reported judging the source and authorship of websites, but other participants
      did not question the source of the information they found online. Although
      personal websites were perceived to be less reliable than those from well-known
      medical institutions, they were still valued by many of the participants.
      Overall, there were relatively few websites about pediatric chronic conditions
      aimed at children, with variable quality and reliability. However, DISCERN's use
      with pediatric websites across a broad spectrum of developmental stages is
      limited. Children and young people demonstrated a need for more guidance around
      assessing trustworthiness of online information. A more appropriate quality
      assessment tool is warranted, which could usefully be employed by health care
      professionals, children, and parents. 

PMID- 24099648
TI  - Breast boost using noninvasive image-guided breast brachytherapy vs. external
      beam: a 2:1 matched-pair analysis.
AB  - BACKGROUND: To compare clinical outcomes and toxicity in patients treated with
      NIBB boost with those in patients treated with external beam (EB) boost. PATIENTS
      AND METHODS: Women with early stage breast cancer treated with WBI and NIBB boost
      were identified. Control subjects treated with EB boost identified as the best
      possible match with respect to age, stage, chemotherapy use, and fractionation
      were chosen for a 2:1 comparison. Acute toxicity, late toxicity, and oncologic
      outcomes were reviewed. The McNemar nonparametric test was used to evaluate
      marginal homogeneity between matched pairs. RESULTS: One hundred forty-one
      patients were included in the analysis: 47 patients treated with NIBB boost and
      94 matched control subjects treated with EB boost (electron, n = 93) or 3-D
      conformal radiation (n = 1). Grade 2+ desquamation developed in 18 patients (39%)
      treated with NIBB boost and in 49 patients (52%) treated with EB boost (P = .07).
      Breast size, electron energy, and fractionation predicted for acute desquamation
      (P < .0001, P < .001, and P = .006). Median follow-up was 13.6 months. One
      patient (2%) who received NIBB had Grade 2+ skin/subcutaneous fibrosis 15 months
      after completion of treatment. Among those treated with EB, 9 patients (9.5%)
      developed Grade 2+ subcutaneous fibrosis, and 1 patient had recurrent cellulitis.
      There was statistically significantly less combined skin/subcutaneous toxicity in
      those treated with NIBB than in those treated with EB (P = .046). CONCLUSION:
      NIBB boost is associated with favorable short-term clinical outcomes compared
      with EB.

PMID- 24099649
TI  - Nab-paclitaxel/bevacizumab/carboplatin chemotherapy in first-line triple negative
      metastatic breast cancer.
AB  - BACKGROUND: Triple negative metastatic breast cancer can be difficult to treat
      with primarily cytotoxic options. Nab-paclitaxel has demonstrated improved PFS
      and tolerability compared with standard cremophor-solubilized paclitaxel; based
      on this, we examined the efficacy and safety of combining weekly nab-paclitaxel
      with carboplatin and bevacizumab in TNMBC. PATIENTS AND METHODS: In this phase
      II, multicenter trial, patients with first-line TNMBC received nab-paclitaxel
      (100 mg/m(2)) and carboplatin (area under the curve = 2) on days 1, 8, 15, and
      bevacizumab (10 mg/kg) on days 1 and 15 of a 28-day cycle. The primary end point
      was safety and tolerability and secondary end points included PFS, ORR, and CBR.
      PFS was calculated using the Kaplan-Meier method. RESULTS: Between July 16, 2007,
      and October 3, 2011, 34 patients were enrolled at 4 centers. Median age was 50.0
      (range, 30-76) years and 77% (n = 26) of patients received previous adjuvant
      therapy. Median PFS was 9.2 months (95% confidence interval [CI], 7.8-25.1
      months). The CBR was 94% (95% CI, 80%-99%), and ORR was 85% (95% CI, 69%-95%) for
      the combination. The regimen was well tolerated with the most common grade 3/4
      adverse events being neutropenia (n = 18; 53%) and thrombocytopenia (n = 6; 18%),
      with other serous events including 1 grade 3 and 1 grade 4 thrombotic event and 1
      febrile neutropenia. CONCLUSION: The combination of nab-paclitaxel, bevacizumab,
      and carboplatin as first-line treatment for TNMBC was efficacious and well
      tolerated. The PFS, CBR, and ORR, and tolerability of the regimen, compares
      favorably with other standard first-line therapies.

PMID- 24099650
TI  - Biochemical and biophysical analysis of a chiral PqsD inhibitor revealing tight
      binding behavior and enantiomers with contrary thermodynamic signatures.
AB  - Antivirulence strategies addressing bacterial pathogenicity without exhibiting
      growth inhibition effects represent a novel approach to overcome today's crisis
      in antibiotic development. In recent studies, we examined various inhibitors of
      PqsD, an enzyme involved in formation of Pseudomonas aeruginosa cell-to-cell
      signaling molecules, and observed desired cellular effects for 2-nitrophenyl
      derivatives. Herein, we investigated the binding characteristics of this
      interesting compound class using several biochemical and biophysical methods. The
      inhibitors showed time-dependent activity, tight-binding behavior, and
      interactions with the catalytic center. Furthermore, isothermal titration
      calorimetry (ITC) experiments with separated enantiomers revealed contrary
      thermodynamic signatures showing either enthalpy- or entropy-driven affinity. A
      combination of site-directed mutagenesis and thermodynamic profiling was used to
      identify key residues involved in inhibitor binding. This information allowed the
      proposal of experimentally confirmed docking poses. Although originally designed
      as transition state analogs, our results suggest an altered position for both
      enantiomers. Interestingly, the main difference between stereoisomers was found
      in the orientation of the hydroxyl group at the stereogenic center. The predicted
      binding modes are in accordance with experimental data and, thus, allow future
      structure-guided optimization. 

PMID- 24099651
TI  - Combining glycosylated hemoglobin A1c and fasting plasma glucose for diagnosis of
      type 2 diabetes in Chinese adults.
AB  - BACKGROUND: Glycosylated hemoglobin A1c (HbA1c) has been applied to identify type
      2 diabetes (T2DM) in the U.S. and European countries. It has not been used in
      China mainly due to lack of a standardized approach to measure HbA1c, short of
      knowledge about racial-specific standard and deficiency of an optimal cut-off
      point. METHODS: To evaluate combination of HbA1c and fasting plasma glucose (FPG)
      in diagnosing T2DM in Chinese adults, a multistage sampling cross-sectional study
      was conducted in Shanghai, China, in 2009. The FPG measurement, HbA1c assay, and
      oral glucose tolerance test (OGTT) were performed in 6,661 Chinese adults (3057
      men, 3604 women) who had no prior history of diabetes to identify the
      unrecognized T2DM. RESULTS: A total of 454 participants were identified as T2DM
      based on the 1999 World Health Organization (WHO) diagnostic criteria. Of these
      patients, 239 were detected using an FPG >= 7.0 mmol/l and 141 were further
      identified using an HbA1c >= 43 mmol/mol (6.1%), achieving a sensitivity of 83.7%
      and a specificity of 89.3% for combining use of FPG and HbA1c. In subjects at
      high risk of diabetes, the combining use of FPG and HbA1c produced a higher
      sensitivity and an improved positive predictive value (PPV), and had a
      satisfactory specificity and negative predictive value (NPV). CONCLUSIONS: The
      combining use of FPG and HbA1c is a potential screening and diagnosis approach
      for T2DM in Chinese adults, especially among those at high risk of the disease.

PMID- 24099652
TI  - First report of Legionella pneumophila in car cabin air filters. Are these a
      potential exposure pathway for professional drivers?
AB  - Recent findings have identified professional drivers as being at an increased
      risk of Legionnaires' disease. Our hypothesis was that used car cabin air filters
      represent a reservoir of Legionella bacteria, and thus a potential pathway for
      contamination. We analysed used cabin air filters from various types of car. The
      filters were analysed by culture and by molecular methods. Our findings indicated
      that almost a third of air filters were colonized with Legionella pneumophila.
      Here, we present the first finding of Legionella spp. in used car cabin air
      filters. Further investigations are needed in order to confirm this exposure
      pathway. The presence of Legionella bacteria in used cabin air filters may have
      been an unknown source of infection until now.

PMID- 24099653
TI  - Lithotripsy for salivary stones with prospective US assessment on our first 25
      consecutive patients.
AB  - OBJECTIVES: To evaluate the predictive value of sonographic fragmentation in the
      successful treatment of sialolithiasis. The main objective was to streamline the
      management by treating the patients with three sessions of ultrasonic
      lithotripsy, and to compare the success rate and complications with data from the
      literature. A second objective was to analyse the predictive value of data from
      the post procedure and follow-up sonography related to therapeutic success with
      regard to size, site and location of stones. MATERIAL AND METHODS: Prospective
      follow-up of 25 patients (mean age of 43 +/- 17.2 years old 11-68; 13 women, 10
      men) over a period of 31 months (October 2009-April 2012) with one or more
      salivary calculi (19 parotid, submandibular 6) treated with extracorporeal
      lithotripsy (electromagnetic MINILITH SL 1, Storz Medical, Switzerland). No
      anaesthesia or analgesia was used. Each session of lithotripsy lasted on average
      30 min. Minor complications were collected on an anonymised sheet. RESULTS:
      Complete success (absence of clinical symptoms 3 months after the end of
      treatment (or the last session) and residual stones <2 mm) was observed in 36% of
      patients, partial success (persistence of symptoms least 3 months (lower
      intensity and lower frequency) or size of residual stones>2 mm) in 48% and
      failure (persistence of same or increased symptoms at 3 months or no change in
      size of the calculi) in 17% of patients. Sonographic fragmentation of the stone
      (p = 0.004), total energy delivered (p = 0.008) and the total number of shock
      waves (n = 0.045) are predictive factors of complete success. Size, salivary
      topography, ductal topography, mobilization of the stones, occurrence of minor
      side effects and total duration of treatment had no predictive value of complete
      success (p > 0.05). There was no significant difference between the first 5 and
      the last 20 patients (p = 0.367). In agreement with the literature data, the
      efficacy of treatment was greater for parotid than submandibular calculi.
      CONCLUSION: Extracorporeal lithotripsy is an alternative to conventional surgery
      with no major complications. Sonographic fragmentation of calculi, total energy
      and total number of shock waves are predictive factors of successful treatment.

PMID- 24099654
TI  - Extraoral approach to mandibular condylar fractures: our experience with 100
      cases.
AB  - INTRODUCTION: Mandibular condylar fractures are very common. The current
      literature contains many indications and methods of treatment. Extraoral
      approaches are complicated by the need to avoid injury to the facial nerve. On
      the other hand intraoral approaches can make fracture reduction and/or fixation
      difficult. The mini-retromandibular approach provides an excellent view of the
      surgical field, minimises the risk of injury to the facial nerve, and allows
      rapid and easy management of condylar fractures. We have collected and reviewed
      our first 100 condylar fractures treated by means of a mini-retromandibular
      approach. PATIENTS AND METHODS: Between June 2006 and June 2012, Eighty-seven
      patients with extracapsular condylar fractures underwent open reduction and rigid
      fixation for 100 extracapsular condylar fractures via a mini-retromandibular
      approach. RESULTS: Dental occlusion and anatomic reduction were restored in all
      100 condylar fractures. Postoperative infection developed in three patients.
      There was one sialocele and one case of plate fracture. Four patients experienced
      transient palsy of the buccal branch of the facial nerve. No permanent deficit of
      any facial nerve branch was observed. No patient showed condylar head resorption.
      CONCLUSIONS: Our experience with the treatment of the first 100 condylar
      fractures using the mini-retromandibular approach has demonstrated that this
      technique has allowed the Authors to safely manage extracapsular condylar
      fractures at all levels.

PMID- 24099655
TI  - Clinical and radiographic evaluation of a computer-generated guiding device in
      bilateral sagittal split osteotomies.
AB  - The bilateral sagittal split osteotomy (BSSO) is one of the main orthognathic
      surgery procedures used for managing skeletal mandibular excess, deficiency or
      asymmetry. It is known to be a technique-sensitive procedure with high reported
      incidences of inferior alveolar nerve injury, bad splits and post-surgical
      relapse. With the increasing use of computer-assisted techniques in orthognathic
      surgery, the accurate transfer of the virtual plan to the operating room is
      currently a subject of research. This study evaluated the efficacy of computer
      generated device at maintaining the planned condylar position and minimizing
      inferior alveolar nerve injury during BSSO. The device was used in 6 patients who
      required isolated mandibular surgery for correction of their skeletal
      deformities. Clinical evaluation showed good recovery of the maximal incisal
      opening and a reproducible occlusion in 5 of the 6 patients. Radiographic
      evaluation showed better control of the condyle position in both the vertical and
      anteroposterior directions than in the mediolateral direction. The degree of
      accuracy between the planned and achieved screw positions were judged as good to
      excellent in all cases. Within the limitations of this study and the small sample
      size, the proposed device design allowed for good transfer of the virtual
      surgical plan to the operating room. 

PMID- 24099656
TI  - [Routine screening for CMV during pregnancy: practices assessment in Ile-de
      France].
AB  - OBJECTIFS: Congenital infection with cytomegalovirus (CMV) is the leading cause
      of materno-fetal viral infection in industrialized countries. It covers up to 1%
      of neonates with risk of sequelae. The recommendations of the National agency for
      accreditation and evaluation in health from 2004 does not support routine
      screening for CMV during pregnancy. Some maternity hospitals still practice this
      screening and the purpose of this work is to present an overview of this practice
      in Ile-de-France. PATIENTS AND METHODS: We present a descriptive cross-sectional
      survey among 99 maternity hospitals of Ile-de-France between July 30, 2011 to
      January 15, 2012. Data were collected using a questionnaire in most cases during
      a telephone interview. Ninety-one questionnaires were collected. The primary
      endpoint was the achievement or otherwise of this screening. RESULTS: Of the 91
      maternity hospitals surveyed, 13 (14.3%) still were conducting this screening in
      2012. This practice was a minority and unrelated to the status (public/private),
      obstetric-pediatric type or activity. DISCUSSION & CONCLUSION: According to
      recent literature data, this diagnosis should be proposed only in case clinical
      or ultrasound signs. Screening could be included as part of research protocol for
      a better understanding of this pathology. It is not recommended in France and
      pending the development of an effective vaccine, informing pregnant women about
      preventive measures appear to be the most effective measure. This will involve a
      wide dissemination of recommendations to general practitioners in first line in
      support of women in early pregnancy.

PMID- 24099657
TI  - Asparagusic acid.
AB  - Asparagusic acid (1,2-dithiolane-4-carboxylic acid) is a simple sulphur
      containing 5-membered heterocyclic compound that appears unique to asparagus,
      though other dithiolane derivatives have been identified in non-food species.
      This molecule, apparently innocuous toxicologically to man, is the most probable
      culprit responsible for the curious excretion of odorous urine following
      asparagus ingestion. The presence of the two adjacent sulphur atoms leads to an
      enhanced chemical reactivity, endowing it with biological properties including
      the ability to substitute potentially for alpha-lipoic acid in alpha-keto-acid
      oxidation systems. This brief review collects the scattered data available in the
      literature concerning asparagusic acid and highlights its properties,
      intermediary metabolism and exploratory applications. 

PMID- 24099658
TI  - Covalent bond formation between amino acids and lignin: cross-coupling between
      proteins and lignin.
AB  - The present study characterized the products formed from the reaction of amino
      acids and in turn, proteins, with lignin resulting in cross-coupling. When added
      to reaction mixtures containing coniferyl alcohol, horseradish peroxidase and
      H2O2, three amino acids (Cys, Tyr, and Thr) are able to form adducts. The low
      molecular weight products were analyzed by HPLC and from each reaction mixture,
      one product was isolated and analyzed by LC/MS. LC/MS results are consistent with
      bond formation between the polar side-chain of these amino acids with Calpha.
      These results are consistent with the cross-coupling of Cys, Tyr and Thr through
      a quinone methide intermediate. In addition to the free amino acids, it was found
      that the cross-coupling of proteins with protolignin through Cys or Tyr residues.
      The findings provide a mechanism by which proteins and lignin can cross-couple in
      the plant cell wall. 

PMID- 24099659
TI  - Efficacy and safety of abiraterone acetate in an elderly patient subgroup (aged
      75 and older) with metastatic castration-resistant prostate cancer after
      docetaxel-based chemotherapy.
AB  - BACKGROUND: Metastatic castration-resistant prostate cancer (mCRPC) is a disease
      that primarily affects older men. Abiraterone acetate (AA), a selective androgen
      biosynthesis inhibitor, in combination with low-dose prednisone (P) improved
      overall survival (OS) in a randomised trial in mCRPC progressing after docetaxel
      versus placebo (PL) plus P. OBJECTIVE: To examine the efficacy and safety of AA
      plus P versus PL plus P in subgroups of elderly (aged >= 75 yr) (n=331) and
      younger patients (<75 yr) (n=863). DESIGN, SETTING, AND PARTICIPANTS: We
      conducted a post hoc analysis of a randomised double-blind PL-controlled study in
      mCRPC patients progressing after docetaxel chemotherapy. INTERVENTION: Patients
      were randomised 2:1 to AA (1000 mg) plus low-dose P (5mg twice daily) (n=797) or
      PL plus P (n=398). OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: Primary end
      point was OS. Secondary end points were time to prostate-specific antigen (PSA)
      progression (TTPP), radiographic progression-free survival (rPFS), and PSA
      response rate. Treatment differences were compared using the stratified log-rank
      test. The Cox proportional hazards model was used to estimate the hazard ratio
      (HR) and 95% confidence interval (CI). The key limitation was the post hoc
      analysis. RESULTS AND LIMITATIONS: Elderly patients treated with AA plus P showed
      improved OS (HR: 0.64; 95% CI, 0.478-0.853; p=0.0022), TTPP (HR: 0.76; 95% CI,
      0.503-1.155; p=0.1995), and rPFS (HR: 0.66; 95% CI, 0.506-0.859; p=0.0019), and
      higher PSA response rate with relative risk (HR: 4.15; 95% CI, 2.2-8.0]; p <=
      0.0001) compared with patients treated with PL plus P. Grade 3/4 adverse events
      occurred in 62% of elderly patients and in 60% of patients aged <75 yr treated
      with AA plus P. Incidences of hypertension and hypokalaemia, although increased
      in the AA plus P arm, were similar in both age subgroups and readily managed.
      CONCLUSIONS: AA improves OS and is well tolerated in both elderly patients and
      younger patients with mCRPC following docetaxel, hence providing an important
      treatment option for elderly patients who may not tolerate alternative therapies
      with greater toxicity. TRIAL REGISTRATION: ClinicalTrials.gov, identifier
      NCT00638690.

PMID- 24099660
TI  - Near-infrared fluorescence imaging: emerging applications in robotic upper
      urinary tract surgery.
AB  - BACKGROUND: Near-infrared fluorescence (NIRF) imaging is a technology with
      emerging applications in urologic surgery. OBJECTIVE: To describe surgical
      techniques and provide clinical outcomes for robotic partial nephrectomy (RPN)
      with selective clamping and robotic upper urinary tract reconstruction featuring
      novel applications of NIRF imaging. DESIGN, SETTING, AND PARTICIPANTS: Data from
      90 patients who underwent successful RPN with selective clamping or upper urinary
      tract reconstruction utilizing NIRF imaging between April 2011 and October 2012
      were reviewed. SURGICAL PROCEDURE: We performed RPN utilizing NIRF imaging to aid
      with selective clamping and upper tract reconstruction with NIRF imaging, the
      details of which are outlined in this paper and the accompanying video. OUTCOME
      MEASUREMENTS AND STATISTICAL ANALYSIS: Patient characteristics, perioperative
      outcomes, and complications were analyzed. RESULTS AND LIMITATIONS: Of the 48 RPN
      patients for whom selective clamping was attempted successfully, median estimated
      blood loss was 200.0 ml, warm ischemia time was 17.0 min, and median change in
      estimated glomerular filtration rate was -6.3%. There was a 12.5% complication
      rate, and all complications were Clavien grade 1-3 (14.3%). The upper urinary
      tract reconstruction utilizing NIRF imaging was performed in 42 patients and
      included pyelopasty (n=20), ureteral reimplant (n=13), ureterolysis (n=7), and
      ureteroureterostomy (n=2). Radiographic and symptomatic improvement was observed
      in 100% of the pyeloplasty, ureteral reimplant, and ureteroureterostomy patients
      and 71.4% of ureterolysis patients, for an overall success rate of 95.2%. This
      study is limited by the small sample size, the short follow-up period, and the
      lack of a comparative cohort. CONCLUSIONS: Our technique of RPN with selective
      arterial clamping and robotic upper urinary tract reconstruction utilizing NIRF
      imaging is presented. This technology provides real-time intraoperative angiogram
      to confirm selective ischemia and may be an adjunct technology to confirm well
      perfused tissue within a reconstruction anastomosis. Further investigation is
      needed to evaluate long-term outcomes of NIRF imaging in robotic upper urinary
      tract surgery and to delineate its indications.

PMID- 24099661
TI  - Photoactivation and saturated emission in blended conjugated polymer
      nanoparticles.
AB  - Blended poly[(9,9-dioctylfluorenyl-2,7-diyl)-co-(1,4-benzo-{2,1',3}-thiadiazole)]
      (PFBT)/poly[2-methoxy-5-(2-ethylhexyloxy)-1,4-phenylenevinylene] (MEH-PPV)
      conjugated polymer nanoparticles were prepared and characterized by conventional
      and single-particle fluorescence spectroscopy. The particles exhibit red emission
      and improved quantum efficiency resulting from highly efficient energy transfer
      from donor PFBT to acceptor MEH-PPV as well as suppression of MEH-PPV
      aggregation. Photobleaching results indicate better photostability in the blended
      sample compared to undoped MEH-PPV nanoparticles and photoactivation of donor
      emission, which could be useful for single-molecule localization-based super
      resolution microscopy. Single blended nanoparticles exhibit bright fluorescence
      as well as saturation behavior at very low excitation intensities. These and
      other properties of the blended conjugated polymer nanoparticles could provide
      substantial improvements in resolution when employed in super-resolution
      microscopy. 

PMID- 24099662
TI  - Deep brain stimulation and ablation for obsessive compulsive disorder: evolution
      of contemporary indications, targets and techniques.
AB  - Surgical therapy for treatment-resistant obsessive compulsive disorder (OCD)
      remains an effective option for well-selected patients managed within a
      multidisciplinary setting. Historically, lesions within the limbic system have
      been used to control both obsessive thoughts and repetitive compulsions
      associated with this disease. We discuss classical targets as well as
      contemporary neuromodulatory approaches that have been shown to provide
      symptomatic relief. Recently, deep brain stimulation (DBS) of the anterior limb
      of the internal capsule/ventral striatum received Conformite Europeene (CE) mark
      and Food and Drug Administration (FDA) approvals for treatment of intractable
      OCD. Remarkably, this is the first such approval for neurosurgical intervention
      in a strictly psychiatric indication in modern times. This target is discussed in
      detail along with alternative targets currently being proposed. We close with a
      discussion of gamma knife capsulotomy, a modality with deep historical roots.
      Further directions in the surgical treatment of OCD will require better
      preoperative predictors of postoperative responses, optimal selection of
      individualized targets, and rigorous reporting of adverse events and standardized
      outcomes. To meet these challenges, centers must be equipped with a
      multidisciplinary team and patient-centered approach to ensure adequate screening
      and follow up of patients with this difficult-to-treat condition. 

PMID- 24099663
TI  - Expression and gene knockdown of zebrafish Ca(2+)/calmodulin-dependent protein
      kinase Idelta-LL.
AB  - Ca(2+)/calmodulin-dependent protein kinase Idelta (CaMKIdelta) is expressed
      ubiquitously, but little is known about its physiological functions. Recently, we
      cloned and characterized two splice variants of zebrafish (Danio rerio)
      CaMKIdelta (CaMKIdelta-S/L). In the present study we cloned a new CaMKIdelta
      isoform, CaMKIdelta-LL, encoded by a different gene from CaMKIdelta-S/L. While
      the catalytic domain of CaMKIdelta-LL showed 86% identity that of CaMKIdelta-S/L,
      it had a unique C-terminal sequence. To clarify the functional role of CaMKIdelta
      LL, we investigated the biological significance of this new isoform during
      zebrafish embryogenesis. Although CaMKIdelta-LL exhibited essentially the same
      catalytic properties and substrate specificities as the other CaMKIdelta
      isoforms, it showed different temporal and spatial expression. During zebrafish
      embryogenesis, RT-PCR analysis detected CaMKIdelta-LL expression after 48 h post
      fertilization. Western blotting in adult zebrafish demonstrated that CaMKIdelta
      LL is expressed in the brain, the eye, and, abundantly, in fins. Knockdown of
      CaMKIdelta-LL expression using morpholino-based antisense oligonucleotides
      resulted in an increase in abnormal embryos with small fins and underdeveloped
      cartilage. These phenotypes were rescued by co-injection with recombinant
      CaMKIdelta-LL. These results clearly indicated that CaMKIdelta-LL plays an
      important role in the generation of cartilage and fins during zebrafish
      embryogenesis.

PMID- 24099664
TI  - Microchip-based detection of magnetically labeled cancer biomarkers.
AB  - Micro-magnetic sensing and actuation have emerged as powerful tools for the
      diagnosis and monitoring of cancer. These technologies can be miniaturized and
      integrated onto compact, microfluidic platforms, enabling molecular diagnostics
      to be performed in practical clinical settings. Molecular targets tagged with
      magnetic nanoparticles can be detected with high sensitivity directly in
      unprocessed clinical samples (e.g. blood, sputum) due to the inherently
      negligible magnetic susceptibility of biological material. As a result, magnetic
      microchip-based diagnostics have been applied with great success to the isolation
      and detection of rare cells and the measurement of sparse soluble proteins. In
      this paper, we review recent advances in microchip-based detection of
      magnetically labeled biomarkers and their translation to clinical applications in
      cancer. 

PMID- 24099665
TI  - Computed tomography screening for lung cancer: results of ten years of annual
      screening and validation of cosmos prediction model.
AB  - INTRODUCTION: It is unclear how long low-dose computed tomographic (LDCT)
      screening should continue in populations at high risk of lung cancer. We assessed
      outcomes and the predictive ability of the COSMOS prediction model in volunteers
      screened for 10 years. MATERIALS AND METHODS: Smokers and former smokers (>20
      pack-years), >50 years, were enrolled over one year (2000-2001), receiving annual
      LDCT for 10 years. The frequency of screening-detected lung cancers was compared
      with COSMOS and Bach risk model estimates. RESULTS: Among 1035 recruited
      volunteers (71% men, mean age 58 years) compliance was 65% at study end. Seventy
      one (6.95%) lung cancers were diagnosed, 12 at baseline. Disease stage was: IA in
      48 (66.6%); IB in 6; IIA in 5; IIB in 2; IIIA in 5; IIIB in 1; IV in 5; and
      limited small cell cancer in 3. Five- and ten-year survival were 64% and 57%,
      respectively, 84% and 65% for stage I. Ten (12.1%) received surgery for a benign
      lesion. The number of lung cancers detected during the first two screening rounds
      was close to that predicted by the COSMOS model, while the Bach model accurately
      predicted frequency from the third year on. CONCLUSIONS: Neither cancer frequency
      nor proportion at stage I decreased over 10 years, indicating that screening
      should not be discontinued. Most cancers were early stage, and overall survival
      was high. Only a limited number of invasive procedures for benign disease were
      performed. The Bach model - designed to predict symptomatic cancers - accurately
      predicted cancer frequency from the third year, suggesting that overdiagnosis is
      a minor problem in lung cancer screening. The COSMOS model - designed to estimate
      screening-detected lung cancers - accurately predicted cancer frequency at
      baseline and second screening round.

PMID- 24099666
TI  - Phase II study of oral S-1 and cisplatin with concurrent radiotherapy for locally
      advanced non-small-cell lung cancer.
AB  - PURPOSE: To determine the efficacy and safety of oral S-1 in combination with
      cisplatin and thoracic radiotherapy in patients with unresectable stage III non
      small-cell lung cancer (NSCLC). METHODS AND MATERIALS: S-1 (50mg/m(2)) was
      administered orally twice daily for 14 days, with cisplatin (40 mg/m(2)) on days
      1 and 8 of each cycle every 3 weeks, for 2-4 cycles. Thoracic radiation therapy
      was administered in 2 Gy fractions five times weekly for a total dose of 60 Gy.
      The primary endpoint was the response rate, and secondary endpoints included
      progression-free survival, overall survival and safety. RESULTS: Forty-one
      patients were enrolled in this study. The objective response rate was 87.8% (98%
      CI: 77.8-97.8%). The median progression-free survival was 467 days (15.4 months),
      and the median survival time was 904 days (29.7 months). The overall survival
      rates at 1- and 2-years were 85.7% and 52.9%, respectively. Hematological
      toxicities included grade 3/4 neutropenia (17%) and grade 3/4 leukopenia (27%).
      No grade 3 febrile neutropenia was detected, and grade 3/4 non-hematological
      toxicities were also mild. A grade 3 gastrointestinal hemorrhage was observed in
      one patient. CONCLUSIONS: The combination of oral S-1 plus cisplatin with
      concurrent radiotherapy is a promising treatment with a high efficacy and lower
      toxicity in patients with locally advanced NSCLC.

PMID- 24099667
TI  - SPatial REgression Analysis of Diffusion tensor imaging (SPREAD) for longitudinal
      progression of neurodegenerative disease in individual subjects.
AB  - OBJECTIVES: To develop a novel statistical method for analysis of longitudinal
      DTI data in individual subjects. MATERIALS AND METHODS: The proposed SPatial
      REgression Analysis of Diffusion tensor imaging (SPREAD) method incorporates a
      spatial regression fitting of DTI data among neighboring voxels and a resampling
      method among data at different times. Both numerical simulations and real DTI
      data from healthy volunteers and multiple sclerosis (MS) patients were used in
      the study to evaluate this method. RESULTS: Statistical inference based on SPREAD
      was shown to perform well through both group comparisons among simulated DTI data
      of individuals (especially when the group size is smaller than 5) and
      longitudinal comparisons of human DTI data within the same individual.
      CONCLUSIONS: When pathological changes of neurodegenerative diseases are
      heterogeneous in a population, SPREAD provides a unique way to assess abnormality
      during disease progression at the individual level. Consequently, it has the
      potential to shed light on how the brain has changed as a result of disease or
      injury.

PMID- 24099669
TI  - Tumor and T cell engagement by BiTE.
AB  - Cancer immunotherapy attempts to exploit the capability of the immune system to
      attack malignant cells. Recent results suggest that clinical responses in
      patients point to this new mechanism as potentially beneficial in harnessing the
      immune system for combating established malignancies. These checkpoint-related
      immunotherapies rely on engaging a subset of T cells in anti-tumor immune
      responses. BiTE(r) (Bi-specific T cell engager) represents a distinct modality
      that directly engages any T cell and a specific antigen expressing tumor cell.
      The approach offers the advantage of engaging T cells and patient tumor cells
      that differentially express a specific cell surface antigen. The specificity
      confers redirected tumor cell killing and recent clinical data with the BiTE
      blinatumomab show evidence of clinical remissions. The characteristics of a
      suitable BiTE with the benefit of CD3 mediated T cell recognition and
      articulation of tumor specific antigens combined in this therapeutic modality is
      described here. 

PMID- 24099668
TI  - Epigenetic silencing of CXCL14 induced colorectal cancer migration and invasion.
AB  - To explore epigenetic regulation and the impact of chemokine CXCL14 on colorectal
      cancer, 7 colorectal cancer cell lines, 107 cases of primary colorectal cancer,
      and 10 cases of normal colorectal mucosa were evaluated in this study.
      Methylation specific PCR (MSP), semi-quantitative reverse-transcription PCR (RT
      PCR), cell proliferation assay, colony formation, and transwell assay were
      performed for the evaluation. Complete methylation and loss of CXCL14 expression
      were found in 5 colorectal cancer cell lines. Partial methylation and weak
      expression were found in two cell lines. CXCL14 was methylated in 79.4% (85/107)
      of primary human colorectal cancer. No methylation was found in 10 cases of
      normal colorectal mucosa. Restoration of CXCL14 expression was induced by the 5
      aza-2'-deoxycytidine (DAC) treatment. The cell viability was reduced and colony
      formation was inhibited by restoration of CXCL14 expression in HCT116 cells, a
      colorectal cancer cell line. The number of invasive and migration cells was
      reduced by CXCL14. The expression of MMP-2, Vimentin, and NF-kappaB was
      suppressed, and the expression of E-cadherin and IkappaB-alpha was induced by
      CXCL14. In conclusion, CXCL14 is frequently methylated in human colorectal cancer
      and promoter region hypermethylation silenced CXCL14 expression in colorectal
      cancer cells. Restoration of CXCL14 expression suppressed colorectal cancer
      proliferation. CXCL14 inhibits colorectal cancer migration, invasion, and
      epithelial-to-mesenchymal transition (EMT) by suppressing NF-kappaB signaling. 

PMID- 24099670
TI  - Scleritis: challenges in immunopathogenesis and treatment.
AB  - Scleritis is an uncommon disease characterized by inflammation of the sclera and
      adjacent ocular structures. Recent studies have led to significant progress in
      understanding the epidemiology, immunopathogenesis, severity assessment,
      treatment, and prognosis of this potentially sight threatening disease. Despite
      these advances, significant challenges remain regarding our understanding of the
      mechanisms of scleral destruction and inflammation, and the rational approach to
      treatment. Information from studies in associated systemic diseases and
      vasculitis and a small number of studies of ocular tissue has revealed the
      prominent role of T and B cells, autoantibodies, immune complexes, and cytokines,
      such as TNF-alpha. These studies have prompted clinical trials that have
      demonstrated the effectiveness of anti-TNF, anti-B cell therapy, systemic
      immunosuppression, and more recently the use of local sub-conjunctival steroid
      treatment. 

PMID- 24099671
TI  - Recent advances in haploidentical stem cell transplantation.
AB  - In the last two decades, new developments in haploidentical hematopoietic stem
      cell transplantation have made it a viable alternative donor option. Initially,
      allogeneic HSCT was limited to patients who had HLA-identical related donors. To
      provide options for patients lacking a matched related donor, registries of
      unrelated volunteer donors or cord blood units have been established with the
      hopes of providing a phenotypically well-matched stem cell product. The use of
      haploidentical donors broadens the application of HSCT more than these other
      approaches. In addition, the greater HLA mismatching associated with
      haploidentical HSCT may potentiate graft versus tumor (GVT) effects. 

PMID- 24099672
TI  - Transverse myelitis--a review of the presentation, diagnosis, and initial
      management.
AB  - Myelitis is a rare neurological disorder of the spinal cord that is caused by
      inflammation and can have devastating neurologic effects with up to two-thirds of
      patients having a moderate to severe degree of residual disability. Symptoms
      typically develop over hours or days and then worsen over a matter of days to
      weeks. Patients can present with sensory alteration, weakness, and autonomic
      dysfunction including bowel and bladder problems, temperature dysregulation, or
      even bouts of hypertension. Evaluation for compressive etiologies must be a
      priority as compressive myelopathy and transverse myelitis are often clinically
      indistinguishable and emergent surgical intervention is indicated in such cases.
      However, if neuroimaging and CSF studies indicate inflammation within the central
      nervous system, then a work-up for myelitis must include autoimmune,
      inflammatory, and infectious etiologies. Acute management of these patients is
      dictated by which etiology is suspected and rapid initiation of that treatment
      portends a more favorable patient outcome. This review will discuss a practical
      clinical approach to the diagnosis and acute management of patients with myelitis
      including clinical symptoms, the role of neuroimaging, and the utility of both
      CSF and serological studies in the management of these patients. 

PMID- 24099673
TI  - Advances in hematopoietic stem cell transplantation in chronic myeloid leukemia.
AB  - Treatment of chronic myeloid leukemia (CML) has evolved dramatically with the
      development of tyrosine kinase inhibitors (TKIs). This past decade also witnessed
      major advances in the field of allogeneic hematopoietic stem cell transplantation
      (alloHSCT) that led to better patients' outcomes. Progress in the exploitation of
      alternative sources of stem cells, development of novel conditioning regimens,
      discovery of innovative graft-versus-host prophylactic strategies, and advances
      in supportive care as well as positioning of alloHSCT in the overall management
      of CML are discussed in this article. 

PMID- 24099674
TI  - Crystal structures of CusC review conformational changes accompanying folding and
      transmembrane channel formation.
AB  - Gram-negative bacteria, such as Escherichia coli, frequently utilize tripartite
      efflux complexes in the RND (resistance-nodulation-cell division) family to expel
      diverse toxic compounds from the cell. These complexes span both the inner and
      outer membranes of the bacterium via an alpha-helical, inner membrane
      transporter; a periplasmic membrane fusion protein; and a beta-barrel, outer
      membrane channel. One such efflux system, CusCBA, is responsible for extruding
      biocidal Cu(I) and Ag(I) ions. To remove these toxic ions, the CusC outer
      membrane channel must form a beta-barrel structural domain, which creates a pore
      and spans the entire outer membrane. We here report the crystal structures of
      wild-type CusC, as well as two CusC mutants, suggesting that the first N-terminal
      cysteine residue plays an important role in protein-membrane interactions and is
      critical for the insertion of this channel protein into the outer membrane. These
      structures provide insight into the mechanisms on CusC folding and transmembrane
      channel formation. It is found that the interactions between CusC and membrane
      may be crucial for controlling the opening and closing of this beta-barrel, outer
      membrane channel. 

PMID- 24099675
TI  - Cranioplasty: plus ca change, plus c'est la meme chose.

PMID- 24099676
TI  - Intraoperative ultrasound-guidance in neurosurgery.

PMID- 24099677
TI  - Development of culturally appropriate pictorial cards to facilitate maternal
      health histories in rural Ghana.

PMID- 24099678
TI  - The status of HBV infection influences metastatic pattern and survival in Chinese
      patients with pancreatic cancer.
AB  - BACKGROUND: It has been proved that hepatitis B virus (HBV) infection alters the
      metastatic pattern and affects survival in colorectal cancer (CRC) and
      hepatocellular carcinoma (HCC), while the influence of HBV infection on
      metastatic pattern and survival in patients with pancreatic cancer (PC) has not
      been investigated yet. METHODS: We conducted an investigation to evaluate the
      impact of HBV infection on metastatic pattern and overall survival in PC. We
      collected the data of 460 PC patients treated in our hospital from 1999 to 2010.
      Serum HBV markers were tested with enzyme-linked immunosorbent assay. The impact
      of HBV infection on metastatic pattern and overall survival was analyzed.
      RESULTS: We found that the incidence of synchronous liver metastasis was
      significantly higher in patients with HBsAg positive than those with HBsAg
      negative (46.0% vs 32.0%, P < 0.05), and higher in chronic HBV infection (CHB)
      group than both non HBV infection and resolved HBV infection group (61.1% vs
      33.9%, P < 0.05, and 61.1% vs 28.7%, P < 0.05, respectively). What's more, Kaplan
      Meier analysis showed that CHB, resolved HBV infection and non HBV infection
      group had significant longer overall survival (OS) compared with inactive HBsAg
      carriers (IC) group (P=0.037, P=0.009, and P=0.019 respectively). But, in the
      multivariate analysis, only the CHB and non HBV infection group had significant
      better overall survival compared with IC group (P=0.010 and P=0.018
      respectively). CONCLUSIONS: Our study found that HBV infection increased
      synchronous liver metastasis rate, and HBV infection status was an independent
      prognostic factor in PC patients.

PMID- 24099679
TI  - Synthesis of pharmacologically active 1-amino-isoquinolines prepared via silver
      triflate-catalyzed cyclization of o-alkynylbenzaldoximes with isocyanates.
AB  - The synthesis of a series of 1-amino-isoquinolines prepared via electrophilic
      cyclization [3+2] cycloaddition/rearrangement reactions of o-alkynylbenzaldoxime
      1 with isocyanates 2 in the presence of catalytic amount of AgOTf was
      demonstrated. The cyclized products were obtained in good yields under an air
      atmosphere. 1-Amino-isoquinoline derivatives 3a, 3b, 3j and 3t were screened in
      vitro for the antioxidant potential and efficacy to inhibit cerebral monoamine
      oxidase (MAO) activity. The antidepressant-like action of some 1-amino
      isoquinolines was performed in the mouse forced swimming test (FST). The
      pharmacological screening of 1-amino-isoquinoline derivatives indicated that 3a,
      3b, 3j and 3t were antioxidants and inhibited cerebral MAO-A and B activities at
      low concentrations. Although at different doses 3a, 3b, 3j and 3t were effective
      antidepressant-like drugs in the mouse FST. None of 1-amino-isoquinolines tested
      caused acute cerebral, hepatic or renal toxicity in mice. 

PMID- 24099680
TI  - Oxygen radical formation in anoxic transgression and anoxia-reoxygenation: foe or
      phantom? Experiments with a hypoxia tolerant bivalve.
AB  - Intertidal blue mussels, Mytilus edulis, experience hypoxia reoxygenation during
      tidal emersion and resubmersion cycles, and this is often suggested to represent
      a major stress for the animals, especially for their respiratory tissues, the
      gills. We exposed mussels to experimental short and prolonged anoxia and
      subsequent reoxygenation and analyzed the respiratory response in excised gill
      tissue and the effects of treatment on reactive oxygen species (mainly ROS:
      superoxide anion, O2.- and hydrogen peroxide, H2O2), formation using live imaging
      techniques and confocal microscopy. Our aim was to understand if this "natural
      stress" would indeed produce oxidative damage and whether antioxidant defenses
      are induced under anoxia, to prevent oxidative damage during reoxygenation.
      Exposure to declining pO2 in the respiration chamber caused an increase of gill
      metabolic rate between 21 and 10 kPa, a pO2 range in which whole animal
      respiration is reported to be oxyregulating. Exposure of the animals to severe
      anoxia caused an onset of anaerobiosis (succinate accumulation) and shifted high
      and low critical pc values (pc1: onset of oxyregulation in gills, pc2: switch
      from oxyregulation to oxyconformity) to higher pO2. Concentrations of both ROS
      decreased strongly during anoxic exposure of the mussels and increased upon
      reoxygenation. This ROS burst induced lipid peroxidation in the mantle, but
      neither were protein carbonyl levels increased (oxidative damage in the protein
      fraction), nor did the tissue glutathione concentration change in the gills.
      Further, analysis of apoptosis markers indicated no induction of cell death in
      the gills. To our knowledge, this is the first paper that directly measures ROS
      formation during anoxia reoxygenation in mussels. We conclude that hypoxia
      tolerant intertidal mussels do not suffer major oxidative stress in gill and
      mantle tissues under these experimental conditions.

PMID- 24099682
TI  - Return to sports after surgery to correct adolescent idiopathic scoliosis: a
      survey of the Spinal Deformity Study Group.
AB  - BACKGROUND CONTEXT: There are no guidelines for when surgeons should allow
      patients to return to sports and athletic activities after spinal fusion for
      adolescent idiopathic scoliosis (AIS). Current recommendations are based on
      anecdotal reports and a survey performed more than a decade ago in the era of
      first/second-generation posterior implants. PURPOSE: To identify current
      recommendations for return to sports and athletic activities after surgery for
      AIS. STUDY DESIGN/SETTING: Questionnaire-based survey. PATIENT SAMPLE: Adolescent
      idiopathic scoliosis after corrective surgery. OUTCOME MEASURES: Type and time to
      return to sports. METHODS: A survey was administered to members of the Spinal
      Deformity Study Group. The survey consisted of surgeon demographic information,
      six clinical case scenarios, three different construct types (hooks, pedicle
      screws, hybrid), and questions regarding the influence of lowest instrumented
      vertebra (LIV) and postoperative physical therapy. RESULTS: Twenty-three surgeons
      completed the survey, and respondents were all experienced expert deformity
      surgeons. Pedicle screw instrumentation allows earlier return to noncontact and
      contact sports, with most patients allowed to return to running by 3 months, both
      noncontact and contact sports by 6 months, and collision sports by 12 months
      postoperatively. For all construct types, approximately 20% never allow return to
      collision sports, whereas all surgeons allow eventual return to contact and
      noncontact sports regardless of construct type. In addition to construct type, we
      found progressively distal LIV resulted in more surgeons never allowing return to
      collision sports, with 12% for selective thoracic fusion to T12/L1 versus 33% for
      posterior spinal fusion to L4. Most respondents also did not recommend formal
      postoperative physical therapy (78%). Of all surgeons surveyed, there was only
      one reported instrumentation failure/pullout without neurologic deficit after a
      patient went snowboarding 2 weeks postoperatively. CONCLUSIONS: Modern posterior
      instrumentation allows surgeons to recommend earlier return to sports after
      fusion for AIS, with the majority allowing running by 3 months, noncontact and
      contact sports by 6 months, and collision sports by 12 months.

PMID- 24099681
TI  - Evolution of system for disability assessment based on the International
      Classification of Functioning, Disability, and Health: A Taiwanese study.
AB  - BACKGROUND/PURPOSE: The criteria for disability were mainly based on the medical
      model, and the candidates for disability benefits were identified by physicians
      mainly depending on their degree of bodily impairment, but without sufficient
      evaluation of their activity, participation, and environment in Taiwan. According
      to the People with Disabilities Rights Protection Act, the assessment of a
      person's eligibility for disability benefits was required to be based on the
      International Classification of Functioning, Disability, and Health (ICF)
      framework since July 11, 2012. This study investigated a proposed system to
      assess patients' eligibility for disability in Taiwan, based on the ICF. METHODS:
      We have initiated a national decision-making process involving members of
      Taiwan's ICF Team. We facilitated 16 group discussions on the ICF coding system,
      in which 199 professionals participated. In each group, one member led the group
      discussion until a consensus was reached. RESULTS: We have developed a process to
      determine the eligibility of people with disabilities. This study set up the
      standards, tools, and practice manuals for each category. We have also developed
      a core set for disability assessment. CONCLUSION: We implemented a new system to
      assess patients' eligibility for disability. The proposed assessment protocol and
      tools require further validation.

PMID- 24099683
TI  - Disease severity and treatment in adolescent idiopathic scoliosis: the impact of
      race and economic status.
AB  - BACKGROUND CONTEXT: Ethnic disparities have been documented in the incidence and
      treatment of many diseases. Additionally, race and socioeconomic status (SES)
      have been shown to affect disease severity and access to care in the recent
      orthopedic literature. PURPOSE: To assess the role, if any, that race, SES, and
      health insurance type play in disease severity and treatment decisions in
      patients with adolescent idiopathic scoliosis. STUDY DESIGN: Retrospective chart
      review. PATIENT SAMPLE: Pediatric patients seen in a single surgeon's practice
      over 6 years (2004-2009). OUTCOME MEASURES: Treatment modality (observation,
      bracing, or surgery). METHODS: Data were obtained from 403 patients seen over 6
      years (2004-2009). A patient-reported questionnaire was used to collect race,
      age, family income, and parent marital status data. Race was self-reported as
      "Asian," "black or African American," "Hispanic or Latino," "white or Caucasian,"
      or "Other." Socioeconomic status was determined using family income and type of
      health insurance as indicators. Major curve magnitude and prescribed initial
      treatment (observation, brace, or surgery) were assessed from physician records.
      An independent sample t test was used to detect differences in curve magnitude of
      the different racial groups. A Pearson chi-square analysis was used to detect
      group differences for curves in surgical patients, defined as curves greater than
      40 degrees , and their initial treatment. RESULTS: Patients self-identified with
      one of the following racial groups: white (N=219), black (N=86), Hispanic (N=44),
      Asian (N=37), or Other (N=17). Mean curve magnitude was greater in black than in
      white patients (33 degrees  vs. 28 degrees , p<.05). Black patients were more
      likely to present with curves in the surgical range (34% vs. 24%, p<.05) and were
      more likely to have surgery as their initial treatment than white patients (34%
      vs. 19%, p<.05). Black patients had more limited health care plans and lower
      incomes compared with whites (p<.001). Patients with higher access insurance
      plans presented at a younger age than patients with more limited access plans,
      irrespective of race (13.6 vs. 14.1, p<.05). There was no difference in Cobb
      angle at presentation by income or type of insurance. CONCLUSIONS: Curve
      magnitude and percentage of patients with curves in the surgical range were
      greater in black than in white patients. There was no difference in age on
      presentation or treatment offered across all racial groups. Black patients were
      more likely to have surgery as their initial treatment than white patients. While
      race did have an impact on disease severity in this single surgeon's practice,
      SES did not.

PMID- 24099684
TI  - Comparison of somatosensory evoked potentials between adolescent idiopathic
      scoliosis and congenital scoliosis without neural axis abnormalities.
AB  - BACKGROUND CONTEXT: Abnormal somatosensory evoked potentials (SEPs) have been
      documented in patients with adolescent idiopathic scoliosis (AIS) with different
      cure severity. However, few studies investigated whether abnormal SEPs were the
      cause or effect of idiopathic scoliosis. PURPOSE: The purpose of this study was
      to investigate the significance of abnormal SEPs in patients with AIS, and to
      explore its effect on the etiopathogenesis of AIS. STUDY DESIGN/SETTING: This
      study evaluated SEPs in patients with AIS and congenital scoliosis (CS) with
      similar curve pattern and severity both in coronal and sagittal planes. PATIENT
      SAMPLE: Female patients with AIS and CS in our spine surgery center from 2000 to
      2009 were recruited for this study. OUTCOME MEASURES: Rate of abnormal SEPs.
      METHODS: Posterior tibial nerve SEPs (PTN-SEPs) were performed on female patients
      with AIS and CS. The inclusion criteria were patients with AIS with a Lenke type
      1 curve and patients with CS with right thoracic curve (apex between T5 and T12)
      and normal sagittal profile (kyphosis less than 50 degrees  measured from T2 to
      T12). All patients were evaluated with total spine magnetic resonance imaging,
      and those with neural axis abnormalities were excluded. The patients with
      neurological deficits on detailed physical examination were also excluded.
      Absence of SEPs waveforms or prolongation of peak latency or asymmetrical peak
      latency were defined as pathological change. The incidence of pathological SEPs
      and clinical characteristics were compared between patients with AIS and patients
      with CS. RESULTS: Forty-six patients with AIS and 33 patients with CS were
      included in this study. There was no significant difference in coronal and
      sagittal Cobb angle between the two groups. The rate of abnormal SEPs was 32.6%
      (15/46) and 12.1% (4/33) in AIS and CS groups, respectively, and the difference
      was statistically significant (p<.05). CONCLUSION: Somatosensory pathway
      dysfunction could be found in both AIS and CS without neural axis abnormalities,
      and the patients with AIS tended to have higher rates of somatosensory disorders
      than patients with CS with similar scoliosis curve, which indicates that both
      scoliosis curve and primary etiopathogenic factor contribute to the sensory
      deficit in patients with AIS.

PMID- 24099685
TI  - The creation of an abbreviated version of the PSEQ: the PSEQ-2.
AB  - BACKGROUND: Self-efficacy is an effective coping strategy associated with less
      pain and disability. The Pain Self-Efficacy Questionnaire (PSEQ) is a valid and
      reliable tool to measure this strategy, but could be inconvenient to implement in
      a busy surgical practice owing to its length. OBJECTIVE: The purpose of this
      study was to develop a shorter version of the 10-item PSEQ. METHODS: A total of
      316 patients (53% men, mean age of 46 y) with a variety of upper extremity
      diagnosis were enrolled in this study. In addition to demographic information,
      patients completed the PSEQ measure of self-efficacy, the QuickDASH measure of
      disability, and an ordinal measure of pain intensity. We conducted inter-item
      correlation analyses for the PSEQ and selected questions based on the magnitude
      of their correlation. RESULTS: Questions 8 and 9 were selected to form the PSEQ
      2. The PSEQ-2 showed good internal consistency (alpha = 0.90) and had a large
      correlation with the original PSEQ (r = 0.76). Both the PSEQ-2 and the original
      PSEQ correlated significantly with QuickDASH and pain intensity. CONCLUSIONS:
      This study provides preliminary evidence that a shortened version of the PSEQ
      might be useful as a screening instrument to identify patients with hand and
      upper extremity conditions who have low self-efficacy and might benefit from
      cognitive behavioral therapy. LEVEL OF EVIDENCE: Diagnostic level III.

PMID- 24099686
TI  - Dermatologic side effects of psychotropic medications.
AB  - BACKGROUND: Although relatively uncommon, cutaneous reactions to psychotropic
      medications may thwart treatment of psychiatric illness and confuse diagnostic
      efforts especially when they occur in the context of comorbid medical conditions.
      Psychiatrists may be asked to comment on whether a particular cutaneous condition
      is due to a psychotropic medication or to recommend a replacement psychotropic
      agent. OBJECTIVE: To review the available literature describing cutaneous adverse
      effects prompted by psychotropic medications. METHOD: A search of the literature
      using PubMed was undertaken using the terms "psychotropic," "psychiatric,"
      "antidepressant," "anxiolytic," "mood stabilizer," "antipsychotic," and
      "neuroleptic" in combination with either of the terms "dermatologic," "cutaneous"
      or "skin." RESULTS: Psychotropic medications from all classes have been
      associated with a broad variety of dermatologic reactions with variable rates of
      incidence. Psychiatrists should be aware of the potential cutaneous adverse
      effects of the medications they prescribe. Psychiatrists practicing in the
      general hospital, where cutaneous symptoms may present for any number of reasons,
      should be aware of the typical presentations and relative likelihood of these
      reactions to forestall unnecessary "blaming" of psychotropics for cutaneous
      reactions.

PMID- 24099688
TI  - Reprint of: high resolution mapping of Y haplogroup G in Tyrol (Austria).
AB  - The distribution of Y-chromosomal haplogroup G2a (G-P15) in present-day paternal
      lineages in Tyrol (Austria) was analyzed by applying a high-density regional
      sampling scheme that also covered remote mountain areas. There is evidence from
      ancient genetic data for a high frequency of Y-chromosomal haplogroup G in
      prehistoric populations of Central Europe, whilst nowadays levels well below 10%
      are routinely observed. A population sample comprising ~3700 specimens was
      analyzed for Y-chromosomal variation by genotyping Y-SNPs and Y-STRs. The set of
      binary markers included nine SNPs specific for sub-lineages of haplogroup G. The
      frequency of haplogroup G in 2379 unrelated men born in Tyrol amounted to 11.3%.
      Nearly all of these Y chromosomes belonged to haplogroup G2a. The main sub
      haplogroup within G2a was defined by the SNP L497 (G2a3b1c) and reached a
      population frequency of 8.6%. Although this average level is higher than reported
      for other countries the geographical distribution of haplogroup G-L497 showed a
      differentiated pattern with a clustered distribution within some alpine valleys,
      where maxima above 40% were found. Both, the estimation of coalescent times and a
      principle coordinates analysis based on RST values derived from Y-STR haplotypes
      from different sub-regions of Tyrol revealed evidence for an old settlement
      history associated with Y chromosomes belonging to haplogroup G in the Tyrolean
      Alps. 

PMID- 24099687
TI  - Ceftriaxone blocks the polymerization of alpha-synuclein and exerts
      neuroprotective effects in vitro.
AB  - The beta-lactam antibiotic ceftriaxone was suggested as a therapeutic agent in
      several neurodegenerative disorders, either for its ability to counteract
      glutamate-mediated toxicity, as in cerebral ischemia, or for its ability to
      enhance the degradation of misfolded proteins, as in Alexander's disease.
      Recently, the efficacy of ceftriaxone in neuroprotection of dopaminergic neurons
      in a rat model of Parkinson's disease was documented. However, which
      characteristics of ceftriaxone mediate its therapeutic effects remains unclear.
      Since, at the molecular level, neuronal alpha-synuclein inclusions and
      pathological alpha-synuclein transmission play a leading role in initiation of
      Parkinson-like neurodegeneration, we thought of investigating, by circular
      dichroism spectroscopy, the capability of ceftriaxone to interact with alpha
      synuclein. We found that ceftriaxone binds with good affinity to alpha-synuclein
      and blocks its in vitro polymerization. Considering this finding, we also
      documented that ceftriaxone exerts neuroprotective action in an in vitro model of
      Parkinson's disease. Our data, in addition to the findings on neuroprotective
      activity of ceftriaxone on Parkinson-like neurodegeneration in vivo, indicates
      ceftriaxone as a potential agent in treatment of Parkinson's disease. 

PMID- 24099689
TI  - Associations of placental weight with maternal and cord blood hormones.
AB  - PURPOSE: Placental weight has been associated with mammographic pattern and
      coronary heart disease in the adult offspring, but the mechanisms are unknown. We
      evaluated the associations of maternal and cord blood hormones with placental
      weight in normal pregnancies. METHODS: Prospective study of 167 normal singleton
      pregnancies in Boston, USA and 256 in Shanghai, China. Maternal hormone levels at
      the 27th gestational week were available for all pregnancies. Cord blood
      measurements were available for 86 pregnancies in Boston and 104 in Shanghai.
      Pearson partial correlation coefficients of log-transformed hormone levels with
      placental weight were calculated. RESULTS: Maternal levels of estriol,
      testosterone, and progesterone (P < .05) were positively associated with
      placental weight. There was no such evidence for adiponectin, prolactin, and
      insulin-like growth factor (IGF)-I. Cord blood steroids tended to be inversely
      associated with placental weight, the results being statistically significant for
      testosterone (P < .05). There was a marginally significant positive association
      of cord blood IGF-I with placental weight. Reported results were adjusted for
      study center. CONCLUSIONS: Placental weight appears to be positively correlated
      with maternal steroids. Its correlation with cord blood steroids, however,
      appears inverse, compatible with negative feedback mechanisms. There is also a
      suggestion for placental weight to be positively associated with cord blood IGF
      I.

PMID- 24099690
TI  - Sex ratio, poverty, and concurrent partnerships among men and women in the United
      States: a multilevel analysis.
AB  - PURPOSE: Social and economic contextual factors may promote concurrent sexual
      partnerships, which can accelerate population HIV transmission and are more
      common among African Americans than U.S. Whites. We investigated the relationship
      between contextual factors and concurrency. METHODS: We analyzed past 12-month
      concurrency prevalence in the 2002 National Survey of Family Growth and its
      contextual database in relation to county sex ratio (among respondent's racial
      and ethnic group), percentage in poverty (among respondent's racial and ethnic
      group), and violent crime rate. Analyses examined counties with balanced (0.95
      1.05 males/female) or low (<0.9) sex ratios. RESULTS: Concurrency prevalence was
      greater (odds ratio [OR]; 95% confidence interval [CI]) in counties with low sex
      ratios (OR, 1.67; 95% CI, 1.17-2.39), more poverty (OR, 1.18; 95% CI, 0.98-1.42
      per 10 percentage-point increase), and higher crime rates (OR, 1.04; 95% CI, 1.00
      1.09 per 1000 population/year). Notably, 99.5% of Whites and 93.7% of Hispanics,
      but only 7.85% of Blacks, lived in balanced sex ratio counties; about 5% of
      Whites, half of Hispanics, and three-fourths of Blacks resided in counties with
      >20% same-race poverty. CONCLUSIONS: The dramatic Black-White differences in
      contextual factors in the United States and their association with sexual
      concurrency could contribute to the nation's profound racial disparities in HIV
      infection.

PMID- 24099691
TI  - Endovascular therapy for young patients with aneurysmal subarachnoid hemorrhage.

PMID- 24099692
TI  - Camptocormia as presenting sign in dementia with Lewy bodies.

PMID- 24099693
TI  - Quantification of chromatin condensation level by image processing.
AB  - The level of chromatin condensation is related to the silencing/activation of
      chromosomal territories and therefore impacts on gene expression. Chromatin
      condensation changes during cell cycle, progression and differentiation, and is
      influenced by various physicochemical and epigenetic factors. This study
      describes a validated experimental technique to quantify chromatin condensation.
      A novel image processing procedure is developed using Sobel edge detection to
      quantify the level of chromatin condensation from nuclei images taken by confocal
      microscopy. The algorithm was developed in MATLAB and used to quantify different
      levels of chromatin condensation in chondrocyte nuclei achieved through
      alteration in osmotic pressure. The resulting chromatin condensation parameter
      (CCP) is in good agreement with independent multi-observer qualitative visual
      assessment. This image processing technique thereby provides a validated unbiased
      parameter for rapid and highly reproducible quantification of the level of
      chromatin condensation. 

PMID- 24099694
TI  - Metal-polybenzimidazole complexes as a nonviral gene carrier: effects of the DNA
      affinity on gene delivery.
AB  - The metal complex-based carriers are emerging likely as a new type of gene
      delivery systems prone to systematic structural alteration and chemical
      tailoring. In our work, the DNA affinity of metal complexes with
      polybenzimidazoles was found to be one of the determinants that can regulate
      expression of the transgenes. Here, the correlations between the DNA affinity and
      transfection efficacy were explored by characterizing gene-delivering properties
      of a series of Co(2+)- and Ca(2+)-polybenzimidazole complexes. The binding
      equilibrium constants (Kobs) of the divalent metal complexes to DNA, which is
      considered as a measure of the DNA affinity of metal complexes, were evaluated by
      isothermal titration calorimetry (ITC) and UV-visible absorption titration. The
      properties of DNA condensates formed with the metal complexes including sizes,
      zeta potential and morphology were observed to be altered with Kobs values. The
      monodispersed spherical condensates were found only for the Ca(2+) complexes
      whose DNA affinity is weaker than that of the Co(2+) complexes. However, the cell
      internalization examination indicated that cell uptake of the DNA condensates is
      independent of homogeneity in their sizes and morphology. The comparison of
      transgene expression showed that that the Ca(2+) complex-mediated transfection
      has higher efficiency than the Co(2+) complexes under the conditions tested, and
      the transfection efficacy cannot be correlated with the cell uptake of DNA
      condensates. Moreover, the Ca(2+) complexes and their DNA condensates had lower
      cytotoxicity than the Co(2+) complexes. Thus, the DNA affinity should be one of
      the factors to be capable of regulating the gene-delivering property of metal
      complexes. 

PMID- 24099695
TI  - Imino-phosphine palladium(II) and platinum(II) complexes: synthesis, molecular
      structures and evaluation as antitumor agents.
AB  - The imino-phosphine ligands L1 and L2 were prepared via condensation reaction of
      2-(diphenylphosphino)benzaldehyde with substituted anilines and obtained in very
      good yields. An equimolar reaction of L1 and L2 with either PdCl2(cod) or
      PtCl2(cod) gave new palladium(II) and platinum(II) complexes 1-4. The compounds
      were characterized by elemental analysis, IR, (1)H and (31)P NMR spectroscopy.
      The molecular structures of 2, 3 and 4 were confirmed by X-ray crystallography.
      All the three molecular structures crystallized in monoclinic C2/c space system.
      The coordination geometry around the palladium and platinum atoms in respective
      structures exhibited distorted square planar geometry at the metal centers. The
      complexes were evaluated in vitro for their cytotoxic activity against human
      breast (MCF-7) and human colon (HT-29) cancer cells, and they exhibited growth
      inhibitory activities and selectivity that were superior to the standard compound
      cisplatin. 

PMID- 24099696
TI  - [Benign conjunctival tumors].
AB  - Benign conjunctival tumors include congenital, melanocytic, epithelial and
      stromal lesions. Clinical observation often fails to make the diagnosis, and
      complete excisional biopsy must be performed as soon as growth is suspected.
      Histology remains the best way to exclude malignancy or lesions with a risk of
      transformation, because malignant lesions carry a poor prognosis and require
      specific therapy and follow-up. Onco-ophthalmologists must have a perfect
      knowledge of benign conjunctival tumors, since during adulthood, nevi can be
      confused with melanomas, and epithelial or stromal lesions with carcinomas. For
      children and teenagers, surgery is only recommended when growth or functional
      problems are observed. 

PMID- 24099697
TI  - [Scintigraphic study of the lymphatic drainage of the anterior chamber of the
      mouse eye and its pathophysiological implications].
AB  - For many years, the intraocular lymphatic system and particularly the drainage of
      the aqueous humor by this system have been considered non-existant. Our study is
      the first to demonstrate, in a dynamic in vivo fashion, the existence of
      lymphatic drainage in the mouse eye. This has become possible with
      lymphoscintigraphy with nano-molecules of rhenium sulphide, marked by technetium
      99m and injected into the anterior chamber of the mouse eye. Readings were taken
      using an experimental gamma camera specially built for the small animal. The
      hypothesis of a "uveolymphatic" drainage pathway within the ciliary body,
      contributing to aqueous outflow, has recently been highlighted by new
      improvements in microbiology (discovery of lymphatic endothelial-specific
      markers) and imaging. This new pathway may lead to many prospects: the
      development of techniques for visualization and quantification of this in vivo
      lymphatic flow may help to increase our understanding of the physiopathology and
      perhaps treatment of chronic glaucoma as well as neoplastic conditions. 

PMID- 24099698
TI  - [Ocular manifestations in chronic granulomatous disease].
AB  - Chronic granulomatous disease (CGD) is a rare genetic immune deficiency due to
      defective oxygen metabolism in phagocytic cells. It results in recurrent severe
      bacterial and fungal infections in patients from an early age on. Inflammatory
      lesions are also observed, with the formation of granulomas. Diagnosis relies on
      the demonstration of a deficiency in the oxidative properties of phagocytes.
      Pulmonary infections are the most frequent clinical manifestations of the
      disease, yet all organs can be involved, such as the eye, with either infections
      or inflammatory chorioretinal lesions. The treatment of CGD relies on prophylaxis
      to avoid infections, and on the rapid management of infectious and inflammatory
      episodes. The only cure to date is allogenetic bone marrow transplant, which
      requires a compatible donor and can only be considered in certain clinical
      situations. 

PMID- 24099699
TI  - [Angiographic appearance of optociliary shunt after central retinal vein
      occlusion].

PMID- 24099700
TI  - Ultrafast photochemistry of anabaena sensory rhodopsin: experiment and theory.
AB  - Light induced isomerization of the retinal chromophore activates biological
      function in all retinal protein (RP) driving processes such as ion-pumping,
      vertebrate vision and phototaxis in organisms as primitive as archea, or as
      complex as mammals. This process and its consecutive reactions have been the
      focus of experimental and theoretical research for decades. The aim of this
      review is to demonstrate how the experimental and theoretical research efforts
      can now be combined to reach a more comprehensive understanding of the excited
      state process on the molecular level. Using the Anabaena Sensory Rhodopsin as an
      example we will show how contemporary time-resolved spectroscopy and recently
      implemented excited state QM/MM methods consistently describe photochemistry in
      retinal proteins. This article is part of a Special Issue entitled: Retinal
      Proteins - You can teach an old dog new tricks. 

PMID- 24099701
TI  - Identification of putative and potential cross-reactive chickpea (Cicer
      arietinum) allergens through an in silico approach.
AB  - BACKGROUND: Allergy has become a key cause of morbidity worldwide. Although many
      legumes (plants in the Fabaceae family) are healthy foods, they may have a number
      of allergenic proteins. A number of allergens have been identified and
      characterized in Fabaceae family, such as soybean and peanut, on the basis of
      biochemical and molecular biological approaches. However, our understanding of
      the allergens from chickpea (Cicer arietinum L.), belonging to this family, is
      very limited. OBJECTIVE: In this study, we aimed to identify putative and cross
      reactive allergens from Chickpea (C. arietinum) by means of in silico analysis of
      the chickpea protein sequences and allergens sequences from Fabaceae family.
      METHODS: We retrieved known allergen sequences in Fabaceae family from the IUIS
      Allergen Nomenclature Database. We performed a protein BLAST (BLASTp) on these
      sequences to retrieve the similar sequences from chickpea. We further analyzed
      the retrieved chickpea sequences using a combination of in silico tools, to
      assess them for their allergenicity potential. Following this, we built structure
      models using FUGUE: Sequence-structure homology; these models generated by the
      recognition tool were viewed in Swiss-PDB viewer. RESULTS: Through this in silico
      approach, we identified seven novel putative allergens from chickpea proteome
      sequences on the basis of similarity of sequence, structure and physicochemical
      properties with the known reported legume allergens. Four out of seven putative
      allergens may also show cross reactivity with reported allergens since potential
      allergens had common sequence and structural features with the reported
      allergens. CONCLUSION: The in silico proteomic identification of the allergen
      proteins in chickpea provides a basis for future research on developing
      hypoallergenic foods containing chickpea. Such bioinformatics approaches,
      combined with experimental methodology, will help delineate an efficient and
      comprehensive approach to assess allergenicity and pave the way for a better
      understanding of the biological and medical basis of the same.

PMID- 24099702
TI  - N-terminal domain of the androgen receptor contains a region that can promote
      cytoplasmic localization.
AB  - Nucleocytoplasmic trafficking of the androgen receptor (AR) represents an
      essential step in androgen action. To determine whether the amino-terminal domain
      (NTD) contains potential nuclear import and/or export signals, deletion mutants
      of the NTD tagged with green fluorescent protein (GFP) were generated and tested
      for their intracellular localization in both AR-negative and AR-positive cell
      lines. Subcellular localization analysis suggested a role of the NTD in
      regulating AR subcellular localization and revealed that the region of a.a. 50
      250 of the NTD of AR (AR(50-250)) could promote cytoplasmic localization.
      Leptomycin B inhibited the activity of AR(50-250), suggesting that AR(50-250)
      export is mediated through exportin 1, either directly or indirectly. These
      observations argue for an important role of the NTD in regulating AR
      nucleocytoplasmic trafficking and will facilitate further investigation of
      interactions among different signals in regulating AR nucleocytoplasmic
      trafficking, which may lead to new approaches to inhibit AR nuclear localization.

PMID- 24099703
TI  - Tragopogon porrifolius improves serum lipid profile and increases short-term
      satiety in rats.
AB  - Tragopogon porrifolius (white salsify) is an edible plant commonly used in folk
      medicine in Lebanon and neighbouring countries. This study investigates the
      effect of the aqueous extract of the aerial part of T. porrifolius on lipemia and
      appetite regulation using a rat model. Food intake, abdominal fat percentage,
      blood lipid profile, liver weight and liver enzymes were assessed following 4
      weeks of extract intake via drinking water (50, 100, or 250 mg/kg body weight) in
      standard high-carbohydrate and high-fat dietary conditions. In a separate study,
      the short term effect of a preload of T. porrifolius extract on food intake was
      evaluated. Results showed that consumption of the plant extract for a period of
      four weeks resulted in a marked improvement of the lipid profile (triglycerides,
      total cholesterol, LDL and HDL cholesterol). Body weight, food intake and intra
      abdominal fat were also lower in animals given the plant extract (100 and 250
      mg/kg). In addition, T. porrifolius extract preload produced a dose dependent
      decrease in food intake observed over 24h. The intake of T. porrifolius aqueous
      extract therefore improved lipemia and increased satiety in rats with no visible
      adverse effects.

PMID- 24099704
TI  - The HOT (Healthy Outcome for Teens) project. Using a web-based medium to
      influence attitude, subjective norm, perceived behavioral control and intention
      for obesity and type 2 diabetes prevention.
AB  - We hypothesized that Theory of Planned Behavior (TPB) constructs (behavioral
      belief, attitude, subjective norm, perceived behavioral control, knowledge and
      behavioral intention) regarding preventive behaviors for obesity and type 2
      diabetes will change favorably after completing the web-based intervention, HOT
      (Healthy Outcome for Teens) project, grounded in the TPB; and that passive online
      learning (POL) group will improve more than the active online learning (AOL)
      group. The secondary hypothesis was to determine to what extent constructs of the
      TPB predict intentions. 216 adolescents were recruited, 127 randomly allocated to
      the treatment group (AOL) and 89 to the control group (POL). The subjects
      completed a TPB questionnaire pre and post intervention. Both POL and AOL groups
      showed significant improvements from pretest to posttest survey. However, the
      results indicated no significant difference between POL and AOL for all
      constructs except behavioral belief. Correlational analysis indicated that all
      TPB constructs were significantly correlated with intentions for pretest and
      posttest for both groups. Attitude and behavioral control showed strongest
      correlations. Regression analysis indicated that TPB constructs were predictive
      of intentions and the predictive power improved post intervention. Behavioral
      control consistently predicted intentions for all categories and was the
      strongest predictor for pretest scores. For posttest scores, knowledge and
      attitude were the strongest predictors for POL and AOL groups respectively. Thus,
      HOT project improved knowledge and the TPB constructs scores for targeted
      behaviors, healthy eating and physical activity, for prevention of obesity and
      type 2 diabetes. 

PMID- 24099705
TI  - The enhanced immune response of hepatitis B virus DNA vaccine using SiO2@LDH
      nanoparticles as an adjuvant.
AB  - Various approaches have been used to improve systemic immune response to
      infectious disease or virus, and DNA vaccination has been demonstrated to be one
      of these effective ways to elicit protective immunity against pathogens. Our
      previous studies showed that layered double hydroxides (LDH) nanoparticles could
      be efficiently taken up by the MDDCs and had an adjuvant activity for DC
      maturation. To further enhance the immune adjuvant activity of LDH, core-shell
      structure SiO2@LDH nanoparticles were synthesized with an average diameter of
      about 210 nm. And its high transfection efficiency in vitro was demonstrated by
      using GFP expression plasmid as model DNA. Exposing SiO2@LDH nanoparticles to
      macrophages caused a higher dose-dependent expression of IFN-gamma, IL-6, CD86
      and MHC II, compared with SiO2 and LDH respectively. Furthermore, in vivo
      immunization of BALB/c mice indicated that, DNA vaccine loaded-SiO2@LDH
      nanoparticles not only induced much higher serum antibody response than naked DNA
      vaccine and plain nanoparticles, but also obviously promoted T-cell proliferation
      and skewed T helper to Th1 polarization. Additionally, it was proved that the
      caveolae-mediated uptake of SiO2@LDH nanoparticles by macrophage lead to
      macrophages activation via NF-kappaB signaling pathway. Our results indicate that
      SiO2@LDH nanoparticles could serve as a potential non-viral gene delivery system.

PMID- 24099707
TI  - Topographic scale-range synergy at the functional bone/implant interface.
AB  - We sought to explore the biological mechanisms by which endosseous implant
      surface topography contributes to bone anchorage. To address this experimentally,
      we implanted five groups of custom-made commercially pure titanium implants of
      varying surface topographical complexity in rat femora for 9 days; subjected them
      to mechanical testing; and then examined the interfacial bone matrix by electron
      microscopy. The five implant surfaces were prepared by combinations of dual acid
      etching and grit blasting the titanium substrates and, in some cases, modifying
      the created surfaces with the deposition of nanocrystals of calcium phosphate,
      which resulted in 10 samples per group. In parallel, we cultured rat bone marrow
      cells on surrogate implants constructed from polymer resin coated with the same
      calcium phosphate nanocrystals, and monitored the deposition of bone sialoprotein
      by transmission electron immunohisto-micrography. We found that implant samples
      modified with sub-micron scale crystals were bone-bonding, as described by the
      interdigitation of a mineralized cement line matrix with the underlying implant
      surface. The in vitro assay showed that bone sialoprotein could be deposited in
      the interstices between, and undercuts below, the nanocrystals. In addition, when
      mineralized, the cement line matrix globules occupied micron-sized pits in the
      implant surfaces, and in part obliterated them, creating an additional form of
      anchorage. Our results also showed that collagen, elaborated by the osteogenic
      cells, wrapped around the coarse-micron features, and became mineralized in the
      normal course of bone formation. This provided a mechanism by which coarse-micron
      implant features contributed to a functional interface, which we have previously
      described, that is capable of resisting the mechanical loading that increases as
      peri-implant bone matures. Thus, our findings provide mechanistic explanations
      for the biologically-relevant criteria that can be employed to assess the
      importance of implant surface topography at different scale-ranges.

PMID- 24099706
TI  - The effect of encapsulation of cardiac stem cells within matrix-enriched hydrogel
      capsules on cell survival, post-ischemic cell retention and cardiac function.
AB  - Transplantation of ex vivo proliferated cardiac stem cells (CSCs) is an emerging
      therapy for ischemic cardiomyopathy but outcomes are limited by modest
      engraftment and poor long-term survival. As such, we explored the effect of
      single cell microencapsulation to increase CSC engraftment and survival after
      myocardial injection. Transcript and protein profiling of human atrial appendage
      sourced CSCs revealed strong expression the pro-survival integrin dimers
      alphaVbeta3 and alpha5beta1- thus rationalizing the integration of fibronectin
      and fibrinogen into a supportive intra-capsular matrix. Encapsulation maintained
      CSC viability under hypoxic stress conditions and, when compared to standard
      suspended CSC, media conditioned by encapsulated CSCs demonstrated superior
      production of pro-angiogenic/cardioprotective cytokines, angiogenesis and
      recruitment of circulating angiogenic cells. Intra-myocardial injection of
      encapsulated CSCs after experimental myocardial infarction favorably affected
      long-term retention of CSCs, cardiac structure and function. Single cell
      encapsulation prevents detachment induced cell death while boosting the
      mechanical retention of CSCs to enhance repair of damaged myocardium. 

PMID- 24099709
TI  - Dual-functional nanoparticles targeting amyloid plaques in the brains of
      Alzheimer's disease mice.
AB  - Alzheimer's disease (AD) is a common neurodegenerative disorder with few
      treatments. The limitations imposed by the blood-brain barrier (BBB) and the non
      selective distribution of drugs in the brain have hindered the effective
      treatment of AD and may result in severe side effects on the normal brains. We
      developed a dual-functional nanoparticle drug delivery system based on a
      PEGylated poly (lactic acid) (PLA) polymer. Two targeting peptides that were
      screened by phage display, TGN and QSH, were conjugated to the surface of the
      nanoparticles. TGN specifically targets ligands at the BBB, while QSH has good
      affinity with Abeta(1-42), which is the main component of amyloid plaque. Tests
      probing the bEnd.3 cell uptake and in vivo imaging were conducted to determine
      the best density of TGN on the nanoparticles' surfaces. The optimal amount of QSH
      was studied using a Thioflavin T (ThT) binding assay and surface plasmon
      resonance (SPR) experiments. The optimal maleimide/peptide molar ratio was 3 for
      both TGN and QSH on the surface of the nanoparticles (T3Q3-NP), and these
      nanoparticles achieved enhanced and precise targeted delivery to amyloid plaque
      in the brains of AD model mice. A MTT assay also validated the safety of this
      dual-targeted delivery system; little cytotoxicity was demonstrated with both
      bEnd.3 and PC 12 cells. In conclusion, the T3Q3-NP might be a valuable targeting
      system for AD diagnosis and therapy.

PMID- 24099708
TI  - Multifunctional silk-heparin biomaterials for vascular tissue engineering
      applications.
AB  - Over the past 30 years, silk has been proposed for numerous biomedical
      applications that go beyond its traditional use as a suture material. Silk
      sutures are well tolerated in humans, but the use of silk for vascular
      engineering applications still requires extensive biocompatibility testing. Some
      studies have indicated a need to modify silk to yield a hemocompatible surface.
      This study examined the potential of low molecular weight heparin as a material
      for refining silk properties by acting as a carrier for vascular endothelial
      growth factor (VEGF) and improving silk hemocompatibility. Heparinized silk
      showed a controlled VEGF release over 6 days; the released VEGF was bioactive and
      supported the growth of human endothelial cells. Silk samples were then assessed
      using a humanized hemocompatibility system that employs whole blood and
      endothelial cells. The overall thrombogenic response for silk was very low and
      similar to the clinical reference material polytetrafluoroethylene. Despite an
      initial inflammatory response to silk, apparent as complement and leukocyte
      activation, the endothelium was maintained in a resting, anticoagulant state. The
      low thrombogenic response and the ability to control VEGF release support the
      further development of silk for vascular applications. 

PMID- 24099711
TI  - Sol-gel silica controlled release thin films for the inhibition of methicillin
      resistant Staphylococcus aureus.
AB  - The incidence of methicillin-resistant Staphylococcus aureus (MRSA) infection has
      significantly increased. Generally, the success of this bacterium as a pathogen
      is attributed to its ability to adhere to surfaces and remain there, under the
      protection of an extracellular matrix known as biofilm. To combat MRSA with
      regular doses of vancomycin, efforts are continuously underway to increase its
      effectiveness. A promising technique is to use combinational therapeutics. In
      vitro experiments showed that farnesol can be used as an adjuvant with
      conventional antibiotics. Farnesol is a natural sesquiterpenoid and quorum
      sensing molecule. The biggest obstacle to using this concept is that farnesol is
      highly water insoluble. This compromises its bioavailability if it were to be
      used along with vancomycin at the site of infection when the treatment needs to
      be administered in vivo. Herein we designed an efficient therapeutic strategy for
      the simultaneous delivery of both antibiotic and adjuvant in order to treat MRSA
      infections. We demonstrate that sufficient quantities of both vancomycin and
      farnesol can be incorporated into sol-gel silica applied as thin films on an
      implant surface. The incorporation of the hydrophobic farnesol does not affect
      the stability of the thin films and neither does it affect the controlled release
      of vancomycin. The data demonstrate the potent adjuvant effect of farnesol on
      vancomycin in inhibiting MRSA infection. In vitro experiments show the complete
      inhibition (10(6) fold reduction in growth compared to control) of methicillin
      sensitive S. aureus (MSSA) and methicillin-resistant S. aureus (MRSA) when the
      ratio of vancomycin to farnesol in the sol-gel silica films is optimized. The
      local delivery of antibiotics minimizes the need for systemic antibiotics. The
      incorporation of vancomycin and farnesol into thin sol-gel films represents a new
      treatment paradigm for the topical delivery of antibiotics with adjuvant. The
      potential clinical benefits are significant and include avoiding the need for
      revision surgery, preventing surgical site infection and controlling healthcare
      costs.

PMID- 24099710
TI  - Particle shape dependence of CD8+ T cell activation by artificial antigen
      presenting cells.
AB  - Previous work developing particle-based acellular, artificial antigen presenting
      cells (aAPCs) has focused exclusively on spherical platforms. To explore the role
      of shape, we generated ellipsoidal PLGA microparticles with varying aspect ratios
      (ARs) and synthesized aAPCs from them. The ellipsoidal biomimetic aAPCs with high
      AR showed significantly enhanced in vitro and in vivo activity above spherical
      aAPCs with particle volume and antigen content held constant. Confocal imaging
      indicates that CD8+ T cells preferentially migrate to and are activated by
      interaction with the long axis of the aAPC. Importantly, enhanced activity of
      high-AR aAPCs was seen in a mouse melanoma model, with high-AR aAPCs improving
      melanoma survival compared to non-cognate aAPCs (p = 0.004) and cognate spherical
      aAPCs (p = 0.05). These findings indicate that particle geometry is a critical
      design criterion in the generation of aAPCs, and may offer insight into the
      essential role of geometry in the interaction between CD8+ T cells and biological
      APCs.

PMID- 24099712
TI  - The effect of bioartificial constructs that mimic myocardial structure and
      biomechanical properties on stem cell commitment towards cardiac lineage.
AB  - Despite the enormous progress in the treatment of coronary artery diseases, they
      remain the most common cause of heart failure in the Western countries. New
      translational therapeutic approaches explore cardiomyogenic differentiation of
      various types of stem cells in combination with tissue-engineered scaffolds. In
      this study we fabricated PHBHV/gelatin constructs mimicking myocardial structural
      properties. Chemical structure and molecular interaction between material
      components induced specific properties to the substrate in terms of
      hydrophilicity degree, porosity and mechanical characteristics. Viability and
      proliferation assays demonstrated that these constructs allow adhesion and growth
      of mesenchymal stem cells (MSCs) and cardiac resident non myocytic cells (NMCs).
      Immunofluorescence analysis demonstrated that stem cells cultured on these
      constructs adopt a distribution mimicking the three-dimensional cell alignment of
      myocardium. qPCR and immunofluorescence analyses showed the ability of this
      construct to direct initial MSC and NMC lineage specification towards
      cardiomyogenesis: both MSCs and NMCs showed the expression of the cardiac
      transcription factor GATA-4, fundamental for early cardiac commitment. Moreover
      NMCs also acquired the expression of the cardiac transcription factors Nkx2.5 and
      TBX5 and produced sarcomeric proteins. This work may represent a new approach to
      induce both resident and non-resident stem cells to cardiac commitment in a 3-D
      structure, without using additional stimuli. 

PMID- 24099713
TI  - Intercondylar roof impingement after anatomic double-bundle anterior cruciate
      ligament reconstruction in patients with knee hyperextension.
AB  - BACKGROUND: Although an anatomically placed graft in anterior cruciate ligament
      (ACL) reconstruction is reported to have a low risk of roof impingement, which
      may cause deterioration of the graft or an extension deficit, the incidence of
      roof impingement by these grafts has not been evaluated in hyperextensible knees.
      PURPOSE: To evaluate the incidence of roof impingement by the native ACL in
      hyperextensible knees and to examine the risk of roof impingement by anatomic
      placement of the ACL graft in hyperextensible knees. STUDY DESIGN: Controlled
      laboratory study. METHODS: Twelve patients were selected for a hyperextensible
      knee group (group A), defined as having hyperextension of the knee of greater
      than 10 degrees . Twelve patients were recruited to a normal extension knee group
      (group B) with normal extension of the knee of less than 5 degrees  of
      hyperextension. Magnetic resonance imaging (MRI) scans of the knee positioned in
      30 degrees  of flexion and full extension were acquired from all patients. The
      shape of the native ACL at full extension was compared between the groups. A 3
      dimensional (3D) bone model was created from the acquired 2D MRI scans. A virtual
      anatomic double-bundle ACL reconstruction in each patient and a virtual anatomic
      single-bundle reconstruction in the patients in group A were performed using the
      3D MRI bone models. The volume of the overlap between the graft and roof was
      calculated to evaluate graft impingement in each instance. RESULTS: The MRI scans
      showed posterior bowing of the native ACL in the group A knees. The simulated
      double-bundle ACL reconstruction showed that the overlapped volume was
      significantly greater in patients in group A than in patients in group B (P <
      .05). However, the overlap of the simulated single-bundle ACL reconstruction was
      significantly less than for the double-bundle ACL reconstruction (P < .05).
      CONCLUSION: To reduce the risk of roof impingement by the graft, single-bundle
      ACL reconstruction with the graft placed at the center of the footprint might be
      the better method for patients with a hyperextensible knee than an anatomic
      double-bundle ACL reconstruction. CLINICAL RELEVANCE: It is recommended that
      surgeons cautiously consider roof impingement after anatomic double-bundle ACL
      reconstruction in patients with a hyperextensible knee.

PMID- 24099714
TI  - Evaluation of suspected child abuse at the ED; implementation of American Academy
      of Pediatrics guidelines in the Netherlands.
AB  - Emergency departments (EDs) are important to detect child physical abuse. A
      structured approach will contribute to an adequate detection of abused children
      at the ED. The American Academy of Pediatrics (AAP) provided guidance in the
      clinical approach to the evaluation of suspected physical abuse in children. In
      the Netherlands, these American Academy of Pediatrics guidelines have been
      adopted for the clinical process of child abuse detection. Here, we describe the
      outcome of the clinical process in the year 2010 with 65 cases of suspected child
      abuse out of 3660 children presenting at an ED, and we discuss the strengths and
      pitfalls of this current clinical approach. 

PMID- 24099715
TI  - Predictors of epinephrine autoinjector needle length inadequacy.
AB  - BACKGROUND: Self-administered epinephrine is the primary out-of-hospital
      treatment of anaphylaxis. Intramuscular injection of epinephrine results in
      higher peak plasma concentration than subcutaneous injection. With the prevalence
      of obesity, autoinjectors may not have an adequate needle length for
      intramuscular injection. OBJECTIVES: To measure muscle depth and evaluate
      predictors of autoinjector needle length inadequacy. METHODS: We performed a
      prospective cross-sectional study of a convenience sample of low acuity emergency
      department patients aged 18 to 55 years. We recorded demographic data, measured
      thigh circumference, and calculated body mass index (BMI). Using ultrasound, we
      took depth-to-muscle measurements of the vastus lateralus in a standing position,
      with and without gentle pressure to simulate muscle compression that occurs with
      correct autoinjector use. We conducted univariate analyses using chi(2) and t
      tests with P <= .05 and 95% confidence intervals. We considered the patient a
      potential "failure" risk if his/her muscle depth exceeded 15.9 mm (longest
      available epinephrine autoinjectors needle). RESULTS: We enrolled 120 subjects
      with a mean BMI of 29.2 kg/m(2). Thirty-one percent (31%) of our sample were
      found to be failure risks (36/116; confidence interval, 22.6%-39.5%). Women were
      6.4 times more likely than men to be a failure risk (54.4% vs 5% for men failure
      rate; P < .001). Failures were more likely to be shorter, have a higher BMI, and
      have larger thigh circumference (P < .001). We did not find any statistical
      difference in muscle depth for race, age, or weight. CONCLUSION: The current
      epinephrine autoinjector needle length is inadequate for intramuscular injection,
      especially among women.

PMID- 24099716
TI  - Integrating health and environmental impact analysis.
AB  - Scientific investigations have progressively refined our understanding of the
      influence of the environment on human health, and the many adverse impacts that
      human activities exert on the environment, from the local to the planetary level.
      Nonetheless, throughout the modern public health era, health has been pursued as
      though our lives and lifestyles are disconnected from ecosystems and their
      component organisms. The inadequacy of the societal and public health response to
      obesity, health inequities, and especially global environmental and climate
      change now calls for an ecological approach which addresses human activity in all
      its social, economic and cultural complexity. The new approach must be integral
      to, and interactive, with the natural environment. We see the continuing failure
      to truly integrate human health and environmental impact analysis as deeply
      damaging, and we propose a new conceptual model, the ecosystems-enriched Drivers,
      Pressures, State, Exposure, Effects, Actions or 'eDPSEEA' model, to address this
      shortcoming. The model recognizes convergence between the concept of ecosystems
      services which provides a human health and well-being slant to the value of
      ecosystems while equally emphasizing the health of the environment, and the
      growing calls for 'ecological public health' as a response to global
      environmental concerns now suffusing the discourse in public health. More
      revolution than evolution, ecological public health will demand new perspectives
      regarding the interconnections among society, the economy, the environment and
      our health and well-being. Success must be built on collaborations between the
      disparate scientific communities of the environmental sciences and public health
      as well as interactions with social scientists, economists and the legal
      profession. It will require outreach to political and other stakeholders
      including a currently largely disengaged general public. The need for an
      effective and robust science-policy interface has never been more pressing.
      Conceptual models can facilitate this by providing theoretical frameworks and
      supporting stakeholder engagement process simplifications for inherently complex
      situations involving environment and human health and well-being. They can be
      tools to think with, to engage, to communicate and to help navigate in a sea of
      complexity. We believe models such as eDPSEEA can help frame many of the issues
      which have become the challenges of the new public health era and can provide the
      essential platforms necessary for progress. 

PMID- 24099717
TI  - Disaccharides in urine samples as markers of intravenous abuse of methadone and
      buprenorphine.
AB  - Methadone and buprenorphine are commonly used as oral substitutes in opiate
      maintenance programs to treat persons who are dependent on heroin. During these
      programs, patients are not allowed to continue using illicit drugs. Abstinence
      can easily be monitored by urine tests with immunochemical methods. It is well
      known that the intravenous abuse of heroin substitutes like methadone or
      buprenorphine has become common as well. The methadone-prescribing physician has
      no opportunity to check whether the opiate maintenance treatment patient takes
      his substitution medicines orally as intended or continues with his intravenous
      misuse now substituting the methadone instead of injecting heroin. In Germany,
      substitutes are available as liquids and tablets that contain carbohydrates as
      adjuvants. Sucrose is used to increase viscosity in liquids, while lactose is
      needed for pressing tablets (e.g., Methaddict(r) and Subutex(r)). In case of oral
      ingestion, disaccharides are broken down into monosaccharides by disaccharidases
      in the small intestine. These monosaccharides are absorbed into the blood stream
      by special monosaccharide transporters. Disaccharidases do not exist in blood,
      thus sucrose and lactose are not split if substitute medicines are injected
      intravenously. Our assumption, therefore, was that they are excreted unchanged in
      urine. We investigated a method for the detection of disaccharides in urine as
      markers of intravenous abuse of substitutes. Urine samples of 26 intravenous
      substitute abusers showed all positive results for lactose (76.9%) and/or sucrose
      (73.1%). The method is assumed to be useful to detect intravenous abuse of
      substitutes.

PMID- 24099718
TI  - Single-cell model of prokaryotic cell cycle.
AB  - One of the recognized prokaryotic cell cycle theories is Cooper-Helmstetter (CH)
      theory which relates start of DNA replication to particular (initiation) cell
      mass, cell growth and division. Different aspects of this theory have been
      extensively studied in the past. In the present study CH theory was applied at
      single cell level. Universal equations were derived for different cell parameters
      (cell mass and volume, surface area, DNA amount and content) depending on
      constructivist cell cycle parameters (unit mass, replication and division times,
      cell age, cell cycle duration) based on selected growth laws of cell mass
      (linear, exponential). The equations derived can be integrated into single-cell
      models for the analysis and design of bacterial cells. 

PMID- 24099719
TI  - Finite element analysis of a femur to deconstruct the paradox of bone curvature.
AB  - Most long limb bones in terrestrial mammals exhibit a longitudinal curvature and
      have been found to be loaded in bending. Bone curvature poses a paradox in terms
      of the mechanical function of limb bones, for many believe the curvature in these
      bones increases bending stress, potentially reducing the bone's load carrying
      capacity (i.e., its mechanical strength). The aim of this study is to investigate
      the role of longitudinal bone curvature in the design of limb bones. In
      particular, it has been hypothesized that bone curvature results in a trade-off
      between the bone's mechanical strength and its bending predictability. We
      employed finite element analysis (FEA) of abstract and realistic human femora to
      address this issue. Geometrically simplified human femur models with different
      curvatures were developed and analyzed with a commercial FEA tool to examine how
      curvature affects the bone's bending predictability and load carrying capacity.
      Results were post-processed to yield probability density functions (PDFs)
      describing the circumferential location of maximum equivalent stress for various
      curvatures in order to assess bending predictability. To validate our findings, a
      finite element model was built from a CT scan of a real human femur and compared
      to the simplified femur model. We found general agreement in trends but some
      quantitative differences most likely due to the geometric differences between the
      digitally reconstructed and the simplified finite element models. As hypothesized
      by others, our results support the hypothesis that bone curvature can increase
      bending predictability, but at the expense of bone strength. 

PMID- 24099720
TI  - A nutrient dependant switch explains mutually exclusive existence of meiosis and
      mitosis initiation in budding yeast.
AB  - Nutrients from living environment are vital for the survival and growth of any
      organism. Budding yeast diploid cells decide to grow by mitosis type cell
      division or decide to create unique, stress resistant spores by meiosis type cell
      division depending on the available nutrient conditions. To gain a molecular
      systems level understanding of the nutrient dependant switching between meiosis
      and mitosis initiation in diploid cells of budding yeast, we develop a
      theoretical model based on ordinary differential equations (ODEs) including the
      mitosis initiator and its relations to budding yeast meiosis initiation network.
      Our model accurately and qualitatively predicts the experimentally revealed
      temporal variations of related proteins under different nutrient conditions as
      well as the diverse mutant studies related to meiosis and mitosis initiation.
      Using this model, we show how the meiosis and mitosis initiators form an all-or
      none type bistable switch in response to available nutrient level (mainly
      nitrogen). The transitions to and from meiosis or mitosis initiation states occur
      via saddle node bifurcation. This bidirectional switch helps the optimal usage of
      available nutrients and explains the mutually exclusive existence of meiosis and
      mitosis pathways. 

PMID- 24099721
TI  - Potential application of granulocyte-colony stimulating factor in the treatment
      of neurological diseases.

PMID- 24099722
TI  - Prevalence and features of peripheral neuropathy in Parkinson's disease patients
      under different therapeutic regimens.
AB  - BACKGROUND: Recent reports suggest increased frequency of peripheral neuropathy
      (PN) in Parkinson's disease (PD) patients on levodopa compared with age-matched
      controls particularly during continuous levodopa delivery by intestinal infusion
      (CLDII). The aim of this study is to compare frequency, clinical features, and
      outcome of PN in PD patients undergoing different therapeutic regimens. METHODS:
      Three groups of consecutive PD patients, 50 on intestinal levodopa (CLDII), 50 on
      oral levodopa (O-LD) and 50 on other dopaminergic treatment (ODT), were enrolled
      in this study to assess frequency of PN using clinical and neurophysiological
      parameters. A biochemical study of all PN patients was performed. RESULTS:
      Frequency of PN of no evident cause was 28% in CLDII, 20% in O-LD, and 6% in ODT
      patients. Clinically, 71% of CLDII patients and all O-LD and ODT PN patients
      displayed a subacute sensory PN. In contrast, 29% of CLDII patients presented
      acute motor PN. Levodopa daily dose, vitamin B12 (VB12) and homocysteine (hcy)
      levels differed significantly in patients with PN compared to patients without
      PN. CONCLUSIONS: Our findings support the relationship between levodopa and PN
      and confirm that an imbalance in VB12/hcy may be a key pathogenic factor. We
      suggest two different, possibly overlapping mechanisms of PN in patients on
      CDLII: axonal degeneration due to vitamin deficiency and inflammatory damage.
      Whether inflammatory damage is triggered by vitamin deficiency and/or by
      modifications in the intestinal micro-environment should be further explored.
      Proper vitamin supplementation may prevent peripheral damage in most cases.

PMID- 24099723
TI  - Reduction in dietary trans fat intake is associated with decreased LDL particle
      number in a primary prevention population.
AB  - BACKGROUND AND AIMS: Increased trans fat intake has been associated with an
      increased risk of cardiovascular disease (CVD). While the effect of trans fat on
      traditional lipids is known, it's association with LDL particle number (LDL-P), a
      novel marker of CVD risk, has not been established. The purpose of this study was
      to determine the association between trans fat intake and LDL-P over 1-year among
      individuals participating in a lifestyle intervention trial. METHODS AND RESULTS:
      Family members (N = 400, 33% male, mean age 48 +/- 13) of patients hospitalized
      with CVD who participated in a 1-year randomized controlled primary prevention
      lifestyle intervention trial and had complete dietary data and LDL-P measures at
      baseline and 1-year. Change in trans fat as a percentage of total diet and mean
      absolute change in LDL-P at 1-year was assessed using multivariate adjusted
      linear regression models. At baseline, there was a significant positive
      correlation between dietary trans fat intake and LDL-P (Beta = 37, p = 0.04). For
      every 1 percent change in trans fat intake there was a 27 nmol/L change in LDL-P
      (Beta = 27, p = 0.04) over 1-year which was independent of baseline predictors
      and confounders (age, sex, smoking, statin use, waist size and physical activity;
      Beta = 30, p = 0.03). CONCLUSION: A reduction in trans fat intake over 1-year was
      significantly associated with a reduction in LDL-P independent of potential
      confounders. Healthcare providers should reinforce the beneficial impact of a
      healthy diet, and in particular modifications in trans fat intake on improving
      lipid profiles.

PMID- 24099724
TI  - Inflammatory status modulates plasma lipid and inflammatory marker responses to
      kiwifruit consumption in hypercholesterolaemic men.
AB  - BACKGROUND AND AIMS: Kiwifruit has the potential to improve markers of metabolic
      dysfunction, but the response may be influenced by inflammatory state. We aimed
      to investigate whether inflammatory state would modulate the effect of consuming
      two green kiwifruit daily on plasma lipids and markers of inflammation. METHODS
      AND RESULTS: Eighty-five hypercholesterolaemic men completed a 4-week healthy
      diet run-in, before randomisation to a controlled cross-over study of two 4-week
      interventions of two green kiwifruit/day plus healthy diet (intervention) or
      healthy diet alone (control). Anthropometric measures and fasting blood samples
      (plasma lipids, serum apolipoproteins A1 and B, high-sensitivity C-reactive
      protein (hs-CRP) and interleukin (IL)-6, tumour necrosis factor-alpha (TNF-alpha)
      and IL-10) were taken at baseline, 4 and 8 weeks. Subjects were divided into low
      and medium inflammatory groups, using pre-intervention hs-CRP concentrations (hs
      CRP <1 and 1-3 mg/L, respectively). In the medium inflammatory group the
      kiwifruit intervention resulted in significant improvements in plasma high
      density lipoprotein cholesterol (HDL-C) (mean difference 0.08 [95% CI: 0.03,
      0.12] mmol/L [P < 0.001]), total cholesterol (TC)/HDL-C ratio (-0.29 [-0.45, 
      0.14] mmol/L [P = 0.001]), plasma hs-CRP (-22.1 [-33.6, -4.97]% [P = 0.01]) and
      IL-6 (-43.7 [-63.0, -14.1]% [P = 0.01]) compared to control treatment. No effects
      were seen in the low inflammatory group. There were significant between
      inflammation group differences for TC/HDL-C (P = 0.02), triglyceride (TG)/HDL-C
      (P = 0.05), and plasma IL-6 (P = 0.04). CONCLUSIONS: Inflammatory state modulated
      responses to the kiwifruit intervention by improving inflammatory markers and
      lipid profiles in subjects with modestly elevated CRP, suggesting this group may
      particularly benefit from the regular consumption of green kiwifruit. Registered
      16th March 2010, Australian New Zealand Clinical Trials Registry (no.
      ACTRN12610000213044), www.ANZCTR.org.au.

PMID- 24099725
TI  - The relationship between nut consumption and blood pressure in an Iranian adult
      population: Isfahan Healthy Heart Program.
AB  - BACKGROUND AND AIMS: Few studies outside of Western countries have evaluated the
      relationship between consumption of nuts and blood pressure (BP). This study
      aimed to investigate the relationship between nut consumption and blood pressure
      in an Iranian adult population. METHODS AND RESULTS: We performed a cross
      sectional investigation among 9660 randomly selected Iranian adults, sampled to
      represent three large Iranian regions, using data collected in the Isfahan
      Healthy Heart Program in 2007. The frequency of nut consumption was assessed by a
      food frequency questionnaire. Systolic and diastolic BPs (SBP and DBP) were
      measured in duplicate by trained personnel using a standard protocol. Multiple
      linear and logistic regressions were applied to assess the relationship between
      nut intake and BP levels and the presence of hypertension as SBP >= 140 mmHg,
      and/or a DBP >= 90 mmHg and/or current use of at least one type of anti
      hypertensive medication. Those with nut consumption >=4 times/week showed less
      mean of BPs and hypertension prevalence, compared to those who consumed nuts <1
      times/week (p < 0.001). Compared to no consumption, consuming nuts >=4 times/week
      was associated with a 34% lower prevalence of hypertension (multivariate odds
      ratio (OR) = 0.66; confidence interval (CI) = 0.51-0.87; p for trend = 0.009).
      CONCLUSIONS: More frequent nut consumption is associated with lower BP and lower
      risk of hypertension among Iranian adults.

PMID- 24099726
TI  - A gender-specific analysis of association between hyperuricaemia and
      cardiovascular events in patients with coronary artery disease.
AB  - BACKGROUND AND AIMS: Gender-related differences in the association between
      hyperuricaemia and cardiovascular events remain poorly understood. The objective
      of this study was to assess gender-related differences in the association between
      hyperuricaemia and cardiovascular events in patients with coronary artery disease
      (CAD). METHODS AND RESULTS: This study included 13,273 patients with CAD.
      Hyperuricaemia was defined as a plasma uric acid >7.0mgdl(-1) in men and
      >5.7mgdl(-1) in women. The primary outcome was 1-year all-cause mortality.
      Hyperuricaemia was found in 3745 men (36.5%) and 1562 women (50.3%); odds ratio
      (OR)=1.76, 95% confidence interval (CI) 1.62-1.91; P<0.001. Women with
      hyperuricaemia were older, had higher proportions of patients with diabetes and
      arterial hypertension and had reduced renal function and higher C-reactive
      protein levels compared with men with hyperuricaemia. One-year all-cause
      mortality was 9.3% (n=143) in women with hyperuricaemia versus 6.9% (n = 252) in
      men with hyperuricaemia (P=0.002). After adjustment in multivariable Cox
      proportional hazards model, uric acid predicted 1-year mortality with an adjusted
      hazard ratio (HR)=1.17, 95% CI (1.03-1.31), P=0.012 in men and HR=1.25, 95% CI
      (1.06-1.48), P=0.007 in women, for each standard deviation increase in the
      natural logarithm. Uric acid predicted 1-year mortality with an area under the
      receiver-operating characteristic curve=0.625, 95% CI (0.594-0.656) in men and
      0.676, 95% CI (0.635-0.717) in women (P=0.044, for women versus men). CONCLUSION:
      Hyperuricaemia predicts an increased risk of 1-year mortality in both genders
      with a stronger association in women. Differences in cardiovascular risk profile
      may explain the stronger association between hyperuricaemia and cardiovascular
      events in women.

PMID- 24099727
TI  - Batch-to-batch reproducibility of TransferonTM.
AB  - Human dialyzable leukocyte extracts (DLEs) are heterogeneous mixtures of low
      molecular-weight peptides that modulate immune responses in various diseases. Due
      their complexity, standardized methods to identify their physicochemical
      properties and determine that production batches are biologically active must be
      established. We aimed to develop and validate a size exclusion ultra performance
      chromatographic (SE-UPLC) method to characterize TransferonTM, a DLE that is
      produced under good manufacturing practices (GMPs). We analyzed an internal human
      DLE standard and 10 representative batches of TransferonTM, all of which had a
      chromatographic profile characterized by 8 main peaks and a molecular weight
      range between 17.0 and 0.2kDa. There was high homogeneity between batches with
      regard to retention times and area percentages, varying by less than 0.2% and
      30%, respectively, and the control chart was within 3 standard deviations. To
      analyze the biological activity of the batches, we studied the ability of
      TransferonTM to stimulate IFN-gamma production in vitro. TransferonTM
      consistently induced IFN-gamma production in Jurkat cells, demonstrating that
      this method can be included as a quality control step in releasing TransferonTM
      batches. Because all analyzed batches complied with the quality attributes that
      were evaluated, we conclude that the DLE TransferonTM is produced with high
      homogeneity. 

PMID- 24099729
TI  - Congenital erosive and vesicular dermatosis with reticulated supple scarring:
      unifying clinical features.
AB  - BACKGROUND: Congenital erosive and vesicular dermatosis (CEVD) healing with
      reticulated supple scarring, a condition usually observed in premature neonates,
      presents at birth with vesicles and erosions. Lesions typically heal within a few
      months, leaving behind scarring with a distinctive supple and reticulated
      texture. OBJECTIVES: We sought to merge existing literature with new cases to
      further define CEVD. METHODS: We analyzed 19 previous reports of CEVD and added 9
      additional patients; we identified unifying characteristics of this cohort.
      RESULTS: In 28 total cases, notable features included: preterm birth (79%), nail
      abnormalities (46%), hyperthermia/hypohidrosis (46%), a history of maternal
      chorioamnionitis (43%), alopecia (43%), neurodevelopmental and ophthalmologic
      abnormalities (36% each), tongue atrophy (29%), or a combination of these.
      Patients with CEVD may be prone to postnatal herpetic superinfections. Previously
      unreported findings included: erosive lichen planus, digital tip gangrene, and
      hydronephrosis. LIMITATIONS: The small patient sampling makes it difficult to
      define diagnostic criteria. As certain findings are associated with prematurity,
      it is unclear to what extent these features result from CEVD, premature birth, or
      another intrauterine pathology. CONCLUSIONS: Although rare, CEVD should be
      considered in the differential diagnosis of neonatal vesicles/erosions in the
      context of a negative infectious workup. This review strengthens the spectrum of
      CEVD features, thus facilitating its recognition by clinicians.

PMID- 24099728
TI  - Long distance directional growth of dopaminergic axons along pathways of netrin-1
      and GDNF.
AB  - Different experimental and clinical strategies have been used to promote survival
      of transplanted embryonic ventral mesencephalic (VM) neurons. However, few
      studies have focused on the long-distance growth of dopaminergic axons from VM
      transplants. The aim of this study is to identify some of the growth and guidance
      factors that support directed long-distance growth of dopaminergic axons from VM
      transplants. Lentivirus encoding either glial cell line-derived neurotrophic
      factor (GDNF) or netrin-1, or a combination of lenti-GDNF with either lenti-GDNF
      family receptor alpha1 (GFRalpha-1) or lenti-netrin-1 was injected to form a
      gradient along the corpus callosum. Two weeks later, a piece of embryonic day 14
      VM tissue was transplanted into the corpus callosum adjacent to the low end of
      the gradient. Results showed that tyrosine hydroxylase (TH(+)) axons grew a very
      short distance from the VM transplants in control groups, with few axons reaching
      the midline. In GDNF or netrin-1 expressing groups, more TH(+) axons grew out of
      transplants and reached the midline. Pathways co-expressing GDNF with either
      GFRalpha-1 or netrin-1 showed significantly increased axonal outgrowth.
      Interestingly, only the GDNF/netrin-1 combination resulted in the majority of
      axons reaching the distal target (80%), whereas along the GDNF/GFRalpha-1 pathway
      only 20% of the axons leaving the transplant reached the distal target. This
      technique of long-distance axon guidance may prove to be a useful strategy in
      reconstructing damaged neuronal circuits, such as the nigrostriatal pathway in
      Parkinson's disease. 

PMID- 24099730
TI  - Current status of surgery in dermatology.
AB  - An article titled "Current issues in dermatologic office-based surgery" was
      published in the JAAD in October 1999 (volume 41, issue 4, pp. 624-634). The
      article was developed by the Joint American Academy of Dermatology/American
      Society for Dermatologic Surgery Liaison Committee. A number of subjects were
      addressed in the article including surgical training program requirements for
      dermatology residents and selected advances in dermatologic surgery that had been
      pioneered by dermatologists. The article concluded with sections on
      credentialing, privileging, and accreditation of office-based surgical
      facilities. Much has changed since 1999, including more stringent requirements
      for surgical training during dermatology residency, and the establishment of 57
      accredited Procedural Dermatology Fellowship Training Programs. All of these
      changes have been overseen and approved by the Residency Review Committee for
      Dermatology and the Accreditation Committee for Graduate Medical Education. The
      fertile academic environment of academic training programs with interaction
      between established dermatologic surgeons and fellows, as well as the inquisitive
      nature of many of our colleagues, has led to the numerous major advances in
      dermatologic surgery, which are described herein.

PMID- 24099731
TI  - Isoquercetin protects cortical neurons from oxygen-glucose deprivation
      reperfusion induced injury via suppression of TLR4-NF-kB signal pathway.
AB  - In the present study, oxygen-glucose deprivation followed by reperfusion (OGD/R),
      an in vitro model of ischemia, was used to evaluate the neuroprotective effect of
      isoquercetin in primary culture of rat cortical neuronal cells. It was found that
      isoquercetin administered prior to the insult could prevent OGD/R-induced
      intracellular calcium concentrations ([Ca(2+)]i) increase, lactate dehydrogenase
      (LDH) release and cell viability decrease. For the first time, isoquercetin is
      described as a neuroprotective agent that potentially explains the alleviation
      and prevention from OGD/R-induced injury in neurons. Mechanistic studies showed
      that the neuroprotective effect of isoquercetin was carried out by anti
      inflammatory signaling pathway of inhibiting protein expression of toll-like
      receptor 4 (TLR4) and nuclear factor-kappa B (NF-kappaB), and mRNA expression of
      TNF-alpha and IL-6, accompanied by the anti-apoptotic signaling pathway of
      deactivation of extracellular-regulated kinase (ERK), Jun kinase (JNK) and p38,
      and inhibition of activity of caspase-3. Therefore, these studies highlighted the
      confirmation of isoquercetin, a flavonoid compound, as an anti-inflammation and
      anti-apoptosis factor which might be used as a therapeutic strategy for the
      ischemia/reperfusion (I/R) brain injury and related diseases. 

PMID- 24099732
TI  - A novel glutamate transporter blocker, LL-TBOA, attenuates ischaemic injury in
      the isolated, perfused rat heart despite low transporter levels.
AB  - OBJECTIVES: Loss of glutamate from cardiomyocytes during ischaemia may aggravate
      ischaemia-reperfusion injury in open heart surgery. This may be due to reversal
      of excitatory amino acid transporters (EAATs). However, the expression of such
      transporters in cardiomyocytes is ambiguous and quantitative data are lacking.
      Our objective was to study whether EAATs were expressed in the rat heart and to
      study whether blocking of transporter operation during cardiac ischaemia could be
      beneficial. METHODS: We used TaqMan real-time PCR and immunoisolation followed by
      western blotting to unequivocally identify EAAT subtypes in rat hearts. We used a
      novel high-affinity non-transportable competitive inhibitor, named LL-TBOA
      [(2S,3S)-3-(3-(6-(6-(2-(2-(2-(2-(2-aminoethoxy)ethoxy)-ethoxy)ethoxy)
      acetamido)hexanamido)- hexanamido)-5-(4-(trifluoromethyl)benzamido)benzyloxy)
      aspartic acid], to block EAAT-mediated transport during global ischaemia and
      reperfusion of isolated rat hearts. RESULTS: Rat hearts expressed EAAT subtypes 1
      and 3, while subtypes 2 and 4 were not detected. Hearts were isolated and
      perfused with 1.6 uM LL-TBOA for 5 min before 30 min of induced global ischaemia
      and 60 min of reperfusion (n = 8). Control hearts were perfused either with the
      solvent dimethylsulfoxide 3.5 mM (n = 7) or with no pretreatment (n = 8). Infarct
      size was evaluated by triphenyl tetrazolium chloride (TTC) staining. LL-TBOA
      reduced infarct size from 33 +/- 14 to 20 +/- 5% (mean +/- SD) (P = 0.015).
      Dimethylsulfoxide alone had no effect (35 +/- 2%). Reperfusion arrhythmias were
      reduced by LL-TBOA (P = 0.009), but not by dimethylsulfoxide alone. CONCLUSION:
      Rat hearts express EAAT1 and EAAT3, but the mRNA levels are, respectively, ~ 25
      and 200 times lower than in the brain. Addition of LL-TBOA has a beneficial
      effect against ischaemia-reperfusion injury.

PMID- 24099733
TI  - Prognostic factors in a multicentre study of 247 atypical pulmonary carcinoids.
AB  - OBJECTIVES: To analyse clinical and biomolecular prognostic factors associated
      with the surgical approach and the outcome of 247 patients affected by primary
      atypical carcinoids (ACs) of the lung in a multi-institutional experience.
      METHODS: We retrospectively evaluated clinical data and pathological tissue
      samples collected from 247 patients of 10 Thoracic Surgery Units from different
      geographical areas of our country. All patients were divided into four groups
      according to surgical procedure: sub-lobar resections (SURG1), lobar resections
      (SURG2), tracheobronchoplastic procedures (SURG3) and pneumonectomies (SURG4).
      Overall survival analysis was performed using the Kaplan-Meier method and log
      rank test. Survival was calculated from the date of surgery to the last date of
      follow-up or death. The parameters evaluated included age, gender, smoking
      habits, laterality, type of surgery, 7th edition of TNM staging, mitosis Ki-67
      (MIB1), multifocal forms, tumourlets, type of lymphadenectomy and neo/adjuvant
      therapy. For multivariate analysis, a Cox regression model was used with a
      forward stepwise selection of covariates. RESULTS: Two hundred and forty-seven
      patients (124 females and 123 males; range 10-84, median 60 years) underwent
      surgical resection for AC in the last 30 years as follows: n = 38 patients in
      SURG1, 181 in SURG2, 15 in SURG3 and 14 in SURG4. A smoking history was present
      in 136 of 247 (55%) patients. The median follow-up period was 98.7 (range 11.2
      369.9) months. The overall survival probability analysis of the AC was 86.7% at 5
      years, 72.4% at 10 years, 64.4% at 15 years and 58.1% at 20 years. Neuroendocrine
      multicentric forms were detected in 12 of 247 patients (4.8%; 1 of 12 pts) during
      the follow-up (range 11.2-200.4, median 98.7 months) and 33.4% had recurrence of
      disease. There were no significant differences between gender, tumour location
      and type of surgery at the multivariate analysis. Age [P < 0.001, hazard ratio
      (HR) 0.60; confidence interval (CI) 0.32-1.12], smoking habits (P = 0.002; HR
      0.43, 95% CI 0.23-0.80) and lymph nodal metastatic involvement (P = 0.008; HR
      0.46, 95% CI 0.26-0.82) were all significant at multivariate analysis.
      CONCLUSIONS: ACs of the lung are malignant neuroendocrine tumours with a worst
      outcome in patients over 70 years and in smokers. With the exception of
      pneumonectomy, the extent of resection does not seem to affect survival and
      should be accompanied preferably by lymphadenectomy. Pathological staging, along
      with a mitotic index more than Ki-67 (MIB1), appears to be the most significant
      prognostic factor at the univariate analysis.

PMID- 24099734
TI  - Outbreak report: nosocomial transmission of measles through an unvaccinated
      healthcare worker-implications for public health.
AB  - BACKGROUND: Nosocomial transmission of measles is a near avoidable event with the
      potential for serious sequelae. Those who acquire infection in hospitals may be
      particularly susceptible to serious disease. UK guidance recommends measles,
      mumps, rubella vaccine (MMR) vaccination for healthcare workers (HCWs) as a key
      preventative measure against nosocomial transmission. We report an incident of
      transmission of measles from a patient to an unvaccinated HCW, with subsequent
      onward transmission to a patient in a paediatric unit. METHODS: Response to the
      incident was undertaken in accordance with guidance from the Health Protection
      Agency (now Public Health England) and UK Department of Health. RESULTS: The
      index case had travelled to France, where there was an ongoing outbreak. There
      were 110 contacts identified for this HCW, of whom 61 were advised to have MMR
      and 5 were given immunoglobulin. All three cases were found to have the same D4
      genotype. CONCLUSIONS: The report highlights the large number of potential
      contacts in a hospital setting and the time and resource implications involved to
      prevent further cases. It also highlights the importance of timely identification
      of measles, early public health notification and complete contact tracing. Such
      incidents are nearly avoidable given the availability of an efficacious vaccine.

PMID- 24099735
TI  - The 'donations for decreased ALT (D4D)' prosocial behavior incentive scheme for
      NAFLD patients.
AB  - BACKGROUND: Physicians often experience difficulties in motivating patients with
      non-alcoholic fatty liver disease (NAFLD) to undergo lifestyle changes. The aim
      of this study is to examine whether 'Donations for Decreased alanine
      aminotransferase (ALT)' (D4D) prosocial behavior incentive can serve as an
      effective intrinsic motivational factor in comparison with conventional dietary
      and exercise intervention alone for NAFLD patients. METHODS: Twenty-five NAFLD
      patients with elevated ALT were randomly assigned to a control group that
      received conventional dietary and exercise intervention alone, or a donation
      group whereby, as an incentive, we would make a monetary donation to the United
      Nations World Food Programme (WFP) based on the decrease in their ALT levels
      achieved over 12 weeks, in addition to receiving control intervention. In a
      donation group, we would donate US$1 to the WFP for every 1 IU/l of decrease in
      their ALT levels. RESULTS: There were no differences of pre-treatment clinical
      characteristics between the two groups. Significant reductions of ALT levels were
      achieved only in a donation group, although post-treatment ALT levels were not
      different between the two groups. These patients raised a total of $316 for the
      WFP. CONCLUSIONS: Promoting patients' intrinsic motivation by incorporating 'D4D'
      prosocial behavior incentive into conventional dietary and exercise intervention
      may provide a means to improve NAFLD.

PMID- 24099736
TI  - Expression of the cannabinoid receptor type 1 in the pituitary of rabbits and its
      role in the control of LH secretion.
AB  - The aim of this study was to elucidate the possible direct regulatory role of the
      endocannabinoids in the modulation of LH secretion in rabbits, a reflex ovulator
      species. The cannabinoid receptor type 1 (CB1) was characterized by RT-PCR
      techniques in the anterior pituitary of intact and ovariectomized does treated
      with GnRH and primed with estrogen and CB1 antagonist, rimonabant. Cannabinoid
      receptor type 1 immune reaction was evidenced by immunohistochemistry in the
      cytoplasm of approximately 10% of the pituitary cells with a density of 8.5 +/-
      1.9 (per 0.01 mm(2)), both periodic acid-Schiff positive (30%) and negative
      (70%). All CB1-immunoreactive cells were also immune reactive for estrogen
      receptor type 1. Ovariectomy, either alone or combined with estrogen priming, did
      not modify the relative abundances of pituitary CB1 mRNA, but decreased (P <
      0.01) the expression of estrogen receptor type 1 mRNA. Treatment with CB1
      antagonist (rimonabant) inhibited (P < 0.01) LH secretory capacity by the
      pituitary after GnRH injection, and estrogen priming had no effect. The present
      findings indicate that the endocannabinoid system is a potential candidate for
      the regulation of the hypothalamic-pituitary-ovarian axis in reflex ovulatory
      species. 

PMID- 24099737
TI  - Heat-tolerant versus heat-sensitive Bos taurus cattle: influence of air
      temperature and breed on the metabolic response to a provocative immune
      challenge.
AB  - The response of the immune and stress systems have been assessed in response to a
      lipopolysaccharide (LPS) challenge, yet the role of metabolism in mediating
      energy requirements during the acute phase response has not been sufficiently
      studied. This study tested heat-tolerant (Romosinuano [RO]) and heat-sensitive
      (Angus [ANG]) Bos taurus breeds at different ambient temperatures (Ta) to
      determine differential metabolic responses to LPS challenge. Twenty-one heifers
      (ANG: n = 11, 306 +/- 26 kg BW; RO: n = 10, 313 +/- 32 kg BW) were housed in
      stanchions in 4 temperature-controlled chambers. Initially, Ta in all 4 chambers
      was cycling at thermoneutrality (TN; 18.5 degrees C-23.5 degrees C) for a 1-wk
      adjustment period, followed by an increase in 2 chambers to cycling heat stress
      (HS; 24 degrees C-38 degrees C) for 2 wk. Five ANG and 5 RO heifers were housed
      at TN, whereas 6 ANG and 5 RO heifers were housed at HS. On day 19, heifers were
      fitted with jugular catheters. On day 20, heifers were challenged with LPS (0.5
      MUg/kg BW; 0 h), and blood samples were collected from -2 to 8 h and at 24 h
      relative to LPS challenge. Serum was analyzed for glucose, insulin, and NEFA
      concentrations. In addition, feed intake was measured 3 d before and on the day
      of the challenge. Feed intake decreased over time (P < 0.001) and was decreased
      in heifers housed at HS compared with heifers housed at TN (P = 0.013). Glucose
      concentrations before LPS challenge were greater in RO (P = 0.01) than in ANG
      heifers and greater in TN-housed heifers (P = 0.02) than in HS heifers. Glucose
      after LPS challenge initially increased before decreasing below baseline
      concentrations (P < 0.01) in all heifers. In addition, there was a breed by Ta
      interaction (P < 0.004), such that HS decreased glucose concentrations in ANG
      heifers compared with ANG heifers housed at TN (P < 0.001), whereas HS did not
      affect glucose concentrations after LPS challenge in RO heifers (P = 0.941).
      Nonesterified fatty acid concentrations before LPS challenge were not affected by
      breed (P = 0.37) or Ta (P = 0.60). Although NEFA concentration after LPS
      challenge was unaffected by Ta (P = 0.78), there tended to be a breed by Ta
      interaction (P = 0.07) such that, when housed at HS, RO heifers had greater serum
      NEFA concentrations after LPS challenge than ANG heifers (P = 0.009). Insulin
      concentration before LPS challenge was greater in RO heifers than in ANG heifers
      (P < 0.01). Insulin after LPS challenge increased (P < 0.01), with RO heifers
      producing a greater insulin response than ANG heifers (P < 0.01). These data
      suggest that HS decreases the metabolic response of heat-sensitive ANG heifers in
      response to LPS challenge, thus providing physiological evidence that may explain
      differences observed in the acute phase response between heat-sensitive ANG and
      heat-tolerant RO cattle breeds. 

PMID- 24099739
TI  - Electrophoretic mobility of sarcoplasmic reticulum vesicles - analytical model
      includes amino acid residues of A+P+N domain of Ca(2+)-ATPase and charged lipids.
AB  - This work is an experimental and theoretical study of electrostatic and
      hydrodynamic properties of the surface of sarcoplasmic reticulum (SR) membrane
      using particle electrophoresis. The essential structural components of SR
      membrane include a lipid matrix and a dense layer of Ca(2+)-ATPases embedded in
      the matrix. The Ca(2+)-ATPase layer both drives and impedes vesicle mobility. To
      analyze the experimental mobility data, obtained at pH4.0, 4.7, 5.0, 6.0, 7.5,
      and 9.0 in 0.1M monovalent (1:1) electrolyte, an analytical solution for the
      vesicle mobility and electroosmotic flow velocity distribution was obtained by
      solving the Poisson-Boltzmann and the Navier-Stokes-Brinkman equations. The
      electrophoretic mobility model includes two sets of charges that represent: (a)
      charged lipids of the lipid matrix of the vesicle core, and (b) charged amino
      acid residues of APN domains of Ca(2+)-ATPases. APN domains are assumed to form a
      charged plane displaced from the surface of lipid matrix. The charged plane is
      embedded in a frictional layer that represents the surface layer of calcium
      pumps. Electrophoretic mobility is driven by the charged APN domain and by lipid
      matrix while the surface layer provides hydrodynamic friction. The charge of APN
      domain is determined by ionized amino acid residues obtained from the amino acid
      composition of SERCA1a Ca(2+)-ATPase. Agreement between the measured and the
      predicted mobility is evaluated by the weighted sum of mobility deviation
      squared. This model reproduces the experimental dependence of mobility on pH and
      predicts that APN domains are located in the upper half of the SR vesicle surface
      layer. 

PMID- 24099738
TI  - Constitutive activation of the Nrf2/Keap1 pathway in insecticide-resistant
      strains of Drosophila.
AB  - Pesticide resistance poses a major challenge for the control of vector-borne
      human diseases and agricultural crop protection. Although a number of studies
      have defined how mutations in specific target proteins can lead to insecticide
      resistance, much less is known about the mechanisms by which constitutive
      overexpression of detoxifying enzymes contributes to metabolic pesticide
      resistance. Here we show that the Nrf2/Keap1 pathway is constitutively active in
      two laboratory-selected DDT-resistant strains of Drosophila, 91R and RDDTR,
      leading to the overexpression of multiple detoxifying genes. Disruption of the
      Drosophila Nrf2 ortholog, CncC, or overexpression of Keap1, is sufficient to
      block this transcriptional response. In addition, a CncC-responsive reporter is
      highly active in both DDT-resistant strains and this response is dependent on the
      presence of an intact CncC binding site in the promoter. Microarray analysis
      revealed that ~20% of the genes differentially expressed in the 91R strain are
      known CncC target genes. Finally, we show that CncC is partially active in these
      strains, consistent with the fitness cost associated with constitutive activation
      of the pathway. This study demonstrates that the Nrf2/Keap1 pathway contributes
      to the widespread overexpression of detoxification genes in insecticide-resistant
      strains and raises the possibility that inhibitors of this pathway could provide
      effective synergists for insect population control. 

PMID- 24099740
TI  - Membrane binding and insertion of the predicted transmembrane domain of human
      scramblase 1.
AB  - Human phospholipid scramblase 1 (SCR) was originally described as an intrinsic
      membrane protein catalyzing transbilayer phospholipid transfer in the absence of
      ATP. More recently, a role as a nuclear transcription factor has been proposed
      for SCR, either in addition or alternatively to its capacity to facilitate
      phospholipid flip-flop. Uncertainties exist as well from the structural point of
      view. A predicted alpha-helix (aa residues 288-306) located near the C-terminus
      has been alternatively proposed as a transmembrane domain, or as a protein core
      structural element. This paper explores the possibilities of the above helical
      segment as a transmembrane domain. To this aim two peptides were synthesized, one
      corresponding to the 19 alpha-helical residues, and one containing both the helix
      and the subsequent 12-residues constituting the C-end of the protein. The
      interaction of these peptides with lipid monolayers and bilayers was tested with
      Langmuir balance surface pressure measurements, proteoliposome reconstitution and
      analysis, differential scanning calorimetry, tests of bilayer permeability, and
      fluorescence confocal microscopy. Bilayers of 28 different lipid compositions
      were examined in which lipid electric charge, bilayer fluidity and lateral
      heterogeneity (domain formation) were varied. All the results concur in
      supporting the idea that the 288-306 peptide of SCR becomes membrane inserted in
      the presence of lipid bilayers. Thus, the data are in agreement with the
      possibility of SCR as an integral membrane protein, without rejecting alternative
      cell locations. 

PMID- 24099741
TI  - Insertion of apoLp-III into a lipid monolayer is more favorable for saturated,
      more ordered, acyl-chains.
AB  - Neutral lipid transport in mammals is complicated involving many types of
      apolipoprotein. The exchangeable apolipoproteins mediate the transfer of
      hydrophobic lipids between tissues and particles, and bind to cell surface
      receptors. Amphipathic alpha-helices form a common structural motif that
      facilitates their lipid binding and exchangeability. ApoLp-III, the only
      exchangeable apolipoprotein found in insects, is a model amphipathic alpha-helix
      bundle protein and its three dimensional structure and function mimics that of
      the mammalian proteins apoE and apoAI. Even the intracellular exchangeable lipid
      droplet protein TIP47/perilipin 3 contains an alpha-helix bundle domain with high
      structural similarity to that of apoE and apoLp-III. Here, we investigated the
      interaction of apoLp-III from Locusta migratoria with lipid monolayers.
      Consistent with earlier work we find that insertion of apoLp-III into fluid lipid
      monolayers is highest for diacylglycerol. We observe a preference for saturated
      and more highly ordered lipids, suggesting a new mode of interaction for
      amphipathic alpha-helix bundles. X-ray reflectivity shows that apoLp-III unfolds
      at a hydrophobic interface and flexible loops connecting the amphipathic alpha
      helices stay in solution. X-ray diffraction indicates that apoLp-III insertion
      into diacylglycerol monolayers induces additional ordering of saturated acyl
      chains. These results thus shed important new insight into the protein-lipid
      interactions of a model exchangeable apolipoprotein with significant implications
      for its mammalian counterparts. 

PMID- 24099742
TI  - Partitioning of lysolipids, fatty acids and their mixtures in aqueous lipid
      bilayers: solute concentration/composition effects.
AB  - Distributions of lysopalmitoylphosphatidylcholine (LPPC), palmitic acid (PA) and
      their 1:1 mixtures between water and dipalmitoylphosphatidylcholine (DPPC)
      bilayer were determined using a fluorescence probe that selectively detects only
      the solutes in water. Water solute concentrations were obtained at each of
      several lipid concentrations. Dynamic Light Scattering experiments confirmed that
      the lipid/solute aggregates were vesicles in the concentration range
      investigated. Lipid concentration dependence of the solute component in water was
      fit to a thermodynamic model of solute distribution between two coexisting
      solvents. Water/bilayer partition coefficient and the free energy of transfer,
      for each of these solutes were determined from the fit. Main findings are: (1)
      Water/bilayer partition coefficient of solute is greater for 2 to 10% solute mole
      fraction than for 0 to 2%, signaling solute induced bilayer perturbation that
      increases bilayer solubility, beginning at 2% solute mole fraction. (2) Partition
      coefficients are in the order LPPC<PA<LPPC+PA at 37 degrees C and
      LPPC+PA<=LPPC<PA at 50 degrees C. This signifies synergism toward increased
      solute solubility in the bilayer-gel phase and lack of it in the bilayer-liquid
      phase when LPPC and PA are present together. Implications of the solute
      concentration/composition and bilayer phase dependences of the partition
      coefficients to the reported solute induced enhancements in transmembrane
      permeability are discussed. 

PMID- 24099743
TI  - Effect of different kinds of anoxia/reoxygenation on the mitochondrial function
      and the free radicals production of cultured primary equine skeletal myoblasts.
AB  - Horses are outstanding athletes, performing in many different disciplines
      involving different kinds of efforts and metabolic responses. Depending on
      exercise intensity, their skeletal muscle oxygenation decreases, and the
      reperfusion at cessation of the exercise can cause excessive production of free
      radicals. This study on cultured primary equine myoblasts investigated the effect
      of different kinds of anoxia/reoxygenation (A/R) on routine respiration,
      mitochondrial complex I specific activity and free radicals production. Our data
      revealed that short cycles of A/R caused a decrease of all the parameters,
      opposite to what a single long period of anoxia did. A preconditioning-like
      effect could explain our first pattern of results whereas mild uncoupling could
      be more appropriate for the second one. Anyway, it seems that mitochondrial
      complex I could play a major role in the regulation of the balance between
      metabolic and antioxidant protection of the muscular function of athletic horses.

PMID- 24099744
TI  - A study of wall shear stress in 12 aneurysms with respect to different viscosity
      models and flow conditions.
AB  - Recent computational fluid dynamics (CFD) studies relate abnormal blood flow to
      rupture of cerebral aneurysms. However, it is still debated how to model blood
      flow with sufficient accuracy. Common assumptions made include Newtonian
      behaviour of blood, traction free outlet boundary conditions and inlet boundary
      conditions based on available literature. These assumptions are often required
      since the available patient specific data is usually restricted to the geometry
      of the aneurysm and the surrounding vasculature. However, the consequences of
      these assumptions have so far been inadequately addressed. This study
      investigates the effects of 4 different viscosity models, 2 different inflow
      conditions and 2 different outflow conditions in 12 middle cerebral artery
      aneurysms. The differences are quantified in terms of 3 different wall shear
      stress (WSS) metrics, involving maximal WSS, average WSS, and proportion of
      aneurysm sac area with low WSS. The results were compared with common geometrical
      metrics such as volume, aspect ratio, size ratio and parent vessel diameter and
      classifications in terms of sex and aneurysm type. The results demonstrate strong
      correlations between the different viscosity models and boundary conditions. The
      correlation between the different WSS metrics range from weak to medium. No
      strong correlations were found between the different WSS metrics and the
      geometrical metrics or classifications. 

PMID- 24099746
TI  - Early and late complications of robot-assisted radical cystectomy: a standardized
      analysis by urinary diversion type.
AB  - PURPOSE: Minimally invasive surgical treatment for bladder cancer has gained
      popularity but standardized data on complications are lacking. Urinary diversion
      type contributes to complications and to our knowledge diversion types after
      minimally invasive cystectomy have not yet been compared. We evaluated
      perioperative complications stratified by urinary diversion type in patients
      treated with robot-assisted radical cystectomy. MATERIALS AND METHODS: We
      analyzed the records of 209 consecutive patients who underwent robot-assisted
      radical cystectomy at our institution from 2003 to 2012 with respect to
      perioperative complications, including severity, time period (early and late) and
      diversion type. All complications were reviewed by academic urologists. Urinary
      diversion was also done. As outcome measurements and statistical analysis,
      univariate and multivariate logistic regression models were used to determine
      predictors of various complications. RESULTS: The American Society of
      Anesthesiologists((r)) (ASA) score was 3 or greater in 80% of patients and
      continent diversion was performed in 68%. Median followup was 35 months. Within
      90 days 77.5% of patients experienced any complication and 32% experienced a
      major complication. The 90-day mortality rate was 5.3%. Most complications were
      gastrointestinal, infectious and hematological. On multivariate analysis patients
      with ileal conduit diversion had a decreased likelihood of complications compared
      to patients with Indiana pouch and orthotopic bladder substitute diversion
      despite the selection of a more comorbid population for conduit diversion.
      Continent diversion was associated with a higher likelihood of urinary tract
      infection. Our results are comparable to those of previously reported open and
      minimally invasive cystectomy series. CONCLUSIONS: Open or minimally invasive
      cystectomy is a complex, morbid procedure. Urinary diversion is a significant
      contributor to complications, as is patient comorbidity. Although patients with
      an ileal conduit had more comorbidities, they experienced fewer complications
      than those with an orthotopic bladder substitute or Indiana pouch diversion.

PMID- 24099747
TI  - Study on the polymer translocation induced blockade ionic current inside a
      nanopore by Langevin dynamics simulation.
AB  - The blockade ionic current inside a nanopore due to polymer translocation is
      studied using a three-dimensional Langevin dynamics method. The blockade current
      IB is dependent on the polymer length N, polymer configuration, polymer-pore
      interaction, and charge of the polymer. The behavior of IB can be explained using
      four factors: (1) the volume vacancy fraction fV inside the pore; (2) the
      conformation of the polymer; (3) the location of the polymer inside the pore; and
      (4) the total charge Ztot inside the pore. We find that IB increases with fV but
      decreases with increasing |Ztot|. The influence of the polymer's conformation is
      complex, dependent on the size of polymer RG and the cross-sectional size of the
      pore s. A compact conformation can decrease IB when RG > s but increase IB when
      RG < s. For the latter case, the conformation of the polymer is too small to
      block the pore, thus providing a broad passage for the ions. At the same fV,
      monomers will locate close to the surface with a large polymer-pore attraction,
      which also provides a large IB. 

PMID- 24099748
TI  - Direction of post-prandial ghrelin response associated with cortisol response,
      perceived stress and anxiety, and self-reported coping and hunger in obese women.
AB  - The neurobiological mechanisms modulating stress may share common pathways with
      appetite regulation and consequent obesity. The orexigenic hormone, ghrelin may
      moderate anxiety and stress-related eating behavior. This study was designed to
      investigate humoral (ghrelin, cortisol) and psychological/behavioral
      characteristics (subjective hunger, anxiety, and stress; eating behavior; coping
      ability) among obese subjects in a fasting state and after eating a standard
      meal. Subjects included 18 obese but otherwise healthy adult women. Subjects were
      divided into two groups based on the relative direction of ghrelin response to a
      standard meal. A meal mediated suppression in serum ghrelin (post/pre<.94) was
      defined as a normal ghrelin response (NG) (n=9) and failure to suppress
      (post/pre>1.0) was designated as faulty ghrelin response (FG) (n=9). Ghrelin and
      cortisol responses were correlated, r(18)=0.558, p=.016. FG subjects had lower
      ratings of coping ability [t(2,16)=2.437, p=.027 and higher ratings of hunger
      cues in the expected direction [t(2,16)=-2.061, p=.056] compared to NG subjects.
      Meal mediated declines in subjective hunger were observed for both NG
      [t(1,8)=4.141, p=.003] and FG [t(1,8)=2.718, p=.026]. NG also showed declines in
      subjective anxiety [t(1,8)=2.977, p=.018], subjective stress [t(1,8)=2.321,
      p=.049], and cortisol [t(1,8)=4.214, p=.003]. In conclusion, changes in ghrelin,
      cortisol and selected psychological and behavioral indices are closely associated
      with one another suggesting that ghrelin may influence stress related eating and
      thus, the consequent observed relationship among stress, mood and obesity. 

PMID- 24099749
TI  - Dalfampridine improves walking speed, walking endurance, and community
      participation in veterans with multiple sclerosis: a longitudinal cohort study.
AB  - BACKGROUND: In short-term trials, dalfampridine extended release (ER) improves
      walking in people with multiple sclerosis (MS). The tolerability and effects of
      dalfampridine-ER in clinical practice have not been reported. OBJECTIVES: The
      objective of this paper is to determine the clinical tolerability and effects of
      dalfampridine on walking and community participation. METHODS: All patients at
      the Portland VA Medical Center prescribed dalfampridine-ER over one year
      completed the Timed 25-Foot Walk (T25FW), Multiple Sclerosis Walking Scale-12
      (MSWS-12), Two-Minute Timed Walk (2MTW), and Community Integration Questionnaire
      (CIQ) at baseline and follow-up clinic visits. Ongoing use and measures over one
      year were analyzed. RESULTS: A total of 39 patients (mean age 56.5 years, mean
      disease duration 19.5 years, 82% male, 38% relapsing-remitting MS, 62%
      progressive MS) were prescribed dalfampridine-ER. Twenty-four (62%) continued to
      take dalfampridine-ER. At initial follow-up, all measures improved significantly
      from baseline (T25FW: -2.7 s, p = 0.004; 2MTW: 41 feet (ft), p = 0.002; MSWS12: 
      11, p < 0.001; CIQ: 1.2, p = 0.003). At one year, walking endurance and self
      perceived walking were still significantly improved (2MTW: 33 ft, p = 0.03; MSWS
      12: 5.9, p = 0.007). CONCLUSIONS: Dalfampridine-ER was associated with short-term
      improvements in walking speed and community participation, and sustained
      improvements in walking endurance and self-perceived impact of MS on walking for
      one year. Our study supports the utility of this medication in late MS.

PMID- 24099750
TI  - Oligoclonal bands and age at onset correlate with genetic risk score in multiple
      sclerosis.
AB  - BACKGROUND: Many genetic risk variants are now well established in multiple
      sclerosis (MS), but the impact on clinical phenotypes is unclear. OBJECTIVE: To
      investigate the impact of established MS genetic risk variants on MS phenotypes,
      in well-characterized MS cohorts. METHODS: Norwegian MS patients (n = 639) and
      healthy controls (n = 530) were successfully genotyped for 61 established MS
      associated single nucleotide polymorphisms (SNPs). Data including and excluding
      Major Histocompatibility Complex (MHC) markers were summed to a MS Genetic Burden
      (MSGB) score. Study replication was performed in a cohort of white American MS
      patients (n = 1997) and controls (n = 708). RESULTS: The total human leukocyte
      antigen (HLA) and the non-HLA MSGB scores were significantly higher in MS
      patients than in controls, in both cohorts (P << 10(-22)). MS patients, with and
      without cerebrospinal fluid (CSF) oligoclonal bands (OCBs), had a higher MSGB
      score than the controls; the OCB-positive patients had a slightly higher MSGB
      than the OCB-negative patients. An early age at symptom onset (AAO) also
      correlated with a higher MSGB score, in both cohorts. CONCLUSION: The MSGB score
      was associated with specific clinical MS characteristics, such as OCBs and AAO.
      This study underlines the need for well-characterized, large cohorts of MS
      patients, and the usefulness of summarizing multiple genetic risk factors of
      modest effect size in genotype-phenotype analyses.

PMID- 24099751
TI  - Brainstem manifestations in neuromyelitis optica: a multicenter study of 258
      patients.
AB  - BACKGROUND: Neuromyelitis optica (NMO) is a severe autoimmune disease of the
      central nervous system characterized by spinal cord and optic nerve involvement.
      Brainstem manifestations have recently been described. OBJECTIVE: To evaluate the
      time of occurrence, the frequency and the characteristics of brainstem symptoms
      in a cohort of patients with NMO according to the ethnic background and the
      serologic status for anti-aquaporin-4 antibodies (AQP4-abs). METHODS: We
      performed a multicenter study of 258 patients with NMO according to the 2006
      Wingerchuk criteria and we evaluated prospectively the frequency, the date of
      onset and the duration of various brainstem signs in this population. RESULTS:
      Brainstem signs were observed in 81 patients (31.4%). The most frequently
      observed signs were vomiting (33.1%), hiccups (22.3%), oculomotor dysfunction
      (19.8%), pruritus (12.4%), followed by hearing loss (2.5%), facial palsy (2.5%),
      vertigo or vestibular ataxia (1.7%), trigeminal neuralgia (2.5%) and other
      cranial nerve signs (3.3%). They were inaugural in 44 patients (54.3%). The
      prevalence was higher in the non-Caucasian population (36.6%) than in the
      Caucasian population (26%) (p<0.05) and was higher in AQP4-ab-seropositive
      patients (32.7%) than in seronegative patients (26%) (not significant).
      CONCLUSIONS: This study confirms the high frequency of brainstem symptoms in NMO
      with a majority of vomiting and hiccups. The prevalence of these manifestations
      was higher in the non Caucasian population.

PMID- 24099752
TI  - Routine aspiration of subglottic secretions after major heart surgery: impact on
      the incidence of ventilator-associated pneumonia.
AB  - Aspiration of subglottic secretions (ASS) is recommended in patients requiring
      mechanical ventilation for >=48h. We assessed the impact of the introduction of
      ASS routinely in all patients after major heart surgery in an ecological study
      comparing ventilator-acquired pneumonia (VAP) incidence, days of mechanical
      ventilation, and cost of antimicrobial agents before and after the implementation
      of ASS. Before and after the intervention the results (per 1000 days) were: VAP
      incidence, 23.92 vs 16.46 (P = 0.04); cost of antimicrobials, ?71,384 vs ?63,446
      (P = 0.002); and days of mechanical ventilation, 507.5 vs 377.5 (P = 0.009). From
      the moment of induction of anaesthesia all patients undergoing major heart
      surgery should routinely receive ASS. 

PMID- 24099753
TI  - Ecotoxicological studies with newly hatched larvae of Concholepas concholepas
      (Mollusca, Gastropoda): bioassay with secondary-treated kraft pulp mill
      effluents.
AB  - The Chilean abalone or "loco" (Concholepas concholepas, Bruguiere 1789) represent
      the most economically important marine recourse exploited from inner inshore
      Management and Exploitation Areas for Benthic Resources along the Chilean coast.
      In this study, newly-hatched larvae of C. concholepas were investigated as a
      potential model species for marine ecotoxicological studies. The study developed
      a behavioral standard protocol for assessing the impact that kraft pulp mill
      effluents after secondary treatment have on C. concholepas larvae. Under
      controlled laboratory conditions, newly-hatched larvae were exposed to a series
      of different concentrations of kraft pulp mill effluents with secondary treatment
      (Pinus spp. and Eucalyptus spp.), potassium dichromate as standard reference
      toxicant and effluent-free control conditions. Regardless of the type of effluent
      the results indicated that diluted kraft pulp effluent with secondary treatment
      had reduced effect on larval survival. Low larval survivals were only recorded
      when they were exposed to high concentrations of the reference toxicant. This
      suggests that C. concholepas larval bioassay is a simple method for monitoring
      the effects of kraft pulp mill effluents with secondary treatment discharged into
      the sea. The results indicated that dilution of ca. 1% of the effluent with an
      elemental chlorine free (ECF) secondary treatment is appropriate for achieving
      low larval mortalities, such as those obtained under control conditions with
      filtered seawater, and to minimize their impact on early ontogenetic stages of
      marine invertebrates such as newly-hatched larvae of C. concholepas. The
      methodological aspects of toxicological testing and behavioral responses
      described here with newly-hatched larvae of C. concholepas can be used to
      evaluate in the future the potential effects of other stressful conditions as
      other pollutants or changes in seawater pH associated with ocean acidification. 

PMID- 24099755
TI  - Long-term survival in patients with germ cell testicular cancer: a population
      based competing-risks regression analysis.
AB  - BACKGROUNDS: Incidence of secondary malignancies and cardiovascular diseases
      among testicular germ cell tumor (TGCT) survivors is higher compared to the
      general population. We sought to describe the rates of other-cancer (OCM), non
      cancer related (NCRM), and cancer-specific mortality (CSM) among men with TGCT.
      METHODS: Using the Surveillance, Epidemiology, and End Results (SEER) database,
      31,330 patients with a primary diagnosis of TGCT between 1973 and 2009 were
      identified. The primary endpoints comprised of 15-year CSM, OCM, and NCRM rates.
      Survival rates were stratified according to histology (seminoma vs. non
      seminoma), median age (<34 vs. >=34 years old), and disease stage (localized vs.
      regional vs. distant). Competing-risks Poisson regression methodologies were
      performed. RESULTS: For seminoma patients, the rates of CSM at 15 years increased
      with advancing stage (0.4-12.6%; P < 0.001), but varies little with age. In
      contrast, the rates of OCM (0.4-7.9%) and NCRM (2.9-8.9%) at 15 years increased
      with advancing stage and age (all P < 0.001). For non-seminoma patients, the 15
      year CSM rates increased with advancing stage and age (1.9-24.4%; all P < 0.001).
      For the same time point, the rates of OCM (0.3-11.4%) and NCRM (2.4-8.0%) also
      increased with age and stage (all P <= 0.001). CONCLUSIONS: The risk of dying
      from secondary malignancies or other causes significantly increases with
      advancing stage and age at diagnosis among TGCT survivors. Such information can
      help provide patients and physicians with better screening strategies, follow-up
      protocols, and mental preparedness for such undesirable effects.

PMID- 24099754
TI  - Identifying important life stages for monitoring and assessing risks from
      exposures to environmental contaminants: results of a World Health Organization
      review.
AB  - In this paper, we summarize exposure-related issues to consider in determining
      the most appropriate age ranges and life stages for risk assessment. We then
      propose a harmonized set of age bins for monitoring and assessing risks from
      exposures to chemicals for global use. The focus is on preconception through
      adolescence, though the approach should be applicable to additional life stages.
      A two-tiered set of early life age groups is recommended. The first tier involves
      the adoption of guidance similar to the childhood age groups recommended by the
      U.S. Environmental Protection Agency, whereas the second tier consolidates some
      of those age groups to reduce the burden of developing age-specific exposure
      factors for different regions. While there is no single "correct" means of
      choosing a common set of age groups to use internationally in assessing early
      life exposure and risk, use of a set of defined age groups is recommended to
      facilitate comparisons of potential exposures and risks around the globe, the
      collection of data and analyses of aggregate exposure and cumulative risk.
      Application of these age groups for robust assessment of exposure and risk for
      specific populations will require region-specific exposure factors as well as
      local environmental monitoring data. 

PMID- 24099756
TI  - Effect of 14 days of bed rest in older adults on parameters of the body sway and
      on the local ankle function.
AB  - This study explored the effects of a 14-day horizontal bed rest (BR) without
      countermeasures on postural sway, maximal voluntary torque and precision of
      voluntary torque matching. Sixteen subjects were tested before, immediately after
      and two weeks after BR. The increase in frequency and amplitude after BR was
      comparable for both sway subcomponents (rambling and trembling) in medial-lateral
      direction. But in anterior-posterior direction, rambling increased more in
      frequency (-7% vs. +31%, p < 0.05) while trembling increased more in amplitude
      (+35% vs. +84%, p < 0.05). The drop in maximal voluntary torque after BR was
      present for plantar flexion (p < 0.05) but not for dorsal flexion. After the BR,
      the subjects were less precise in the dorsal flexion torque matching task (p <
      0.05). All the observed parameters, except the dorsal flexion torque matching
      error, returned back to the pre-BR values after the two weeks of re-conditioning.
      Results of this study indicate that body sway subcomponents responded differently
      to BR. Based on these findings, it was not possible to draw clear assumptions on
      the effects of neural and structural changes on body sway.

PMID- 24099758
TI  - Pulmonary oedema mimicking bronchiectasis.
AB  - A previously completely fit and well 62-year-old man presented with a 4-week
      history of lethargy and increasing shortness of breath. This had been preceded by
      a flu-like illness that had been treated in the community with ciprofloxacin to
      no effect. There was no history of smoking, tuberculosis exposure or significant
      exposure to birds. Clinically the patient appeared well and was comfortable and
      conversant with no peripheral oedema. Chest auscultation revealed normal breath
      sounds and a loud pansystolic murmur over the cardiac apex. A chest radiograph
      and a subsequent CT scan showed widespread fibrotic and bronchiectatic changes,
      predominantly in the right upper lobe, with bilateral pleural effusions.
      Echocardiography revealed a posterior mitral valve prolapse. He was treated with
      loop diuretics and a mitral valve repair that resolved his symptoms and
      radiographic findings. This is the first English language case report of
      pulmonary oedema causing bronchiectatic lung appearances. 

PMID- 24099757
TI  - Common mechanistic themes for the powerstroke of kinesin-14 motors.
AB  - Kar3Cik1 is a heterodimeric kinesin-14 from Saccharomyces cerevisiae involved in
      spindle formation during mitosis and karyogamy in mating cells. Kar3 represents a
      canonical kinesin motor domain that interacts with microtubules under the control
      of ATP-hydrolysis. In vivo, the localization and function of Kar3 is
      differentially regulated by its interacting stoichiometrically with either Cik1
      or Vik1, two closely related motor homology domains that lack the nucleotide
      binding site. Indeed, Vik1 structurally resembles the core of a kinesin head.
      Despite being closely related, Kar3Cik1 and Kar3Vik1 are each responsible for a
      distinct set of functions in vivo and also display different biochemical behavior
      in vitro. To determine a structural basis for their distinct functional
      abilities, we used cryo-electron microscopy and helical reconstruction to
      investigate the 3-D structure of Kar3Cik1 complexed to microtubules in various
      nucleotide states and compared our 3-D data of Kar3Cik1 with that of Kar3Vik1 and
      the homodimeric kinesin-14 Ncd from Drosophila melanogaster. Due to the lack of
      an X-ray crystal structure of the Cik1 motor homology domain, we predicted the
      structure of this Cik1 domain based on sequence similarity to its relatives Vik1,
      Kar3 and Ncd. By molecular docking into our 3-D maps, we produced a detailed near
      atomic model of Kar3Cik1 complexed to microtubules in two distinct nucleotide
      states, a nucleotide-free state and an ATP-bound state. Our data show that
      despite their functional differences, heterodimeric Kar3Cik1 and Kar3Vik1 and
      homodimeric Ncd, all share striking structural similarities at distinct
      nucleotide states indicating a common mechanistic theme within the kinesin-14
      family. 

PMID- 24099759
TI  - Association of membranoproliferative glomerulonephritis with mantle cell
      lymphoma.
AB  - Mantle cell lymphoma (MCL) is a rare and aggressive lymphoid neoplasm. It can
      involve the kidney, either by direct lymphomatous infiltration or by a
      paraneoplastic glomerulonephritis. We present here the case of a man with rectal
      bleeding and rapidly progressive renal failure, who had MCL in the
      gastrointestinal tract and paraneoplastic membranoproliferative
      glomerulonephritis, and whose renal dysfunction normalised after chemotherapy. 

PMID- 24099760
TI  - Lucky to meet RS3PE.
AB  - We present a florid case of remitting seronegative symmetrical synovitis with
      pitting edema that was actually a paraneoplastic syndrome of an asymptomatic
      undiagnosed adenosquamous lung cell carcinoma. The arthritis led to a screening
      for lung cancer and an early enough diagnosis for a curative intervention. 

PMID- 24099761
TI  - Occurrence of Guillain-Barre syndrome as an immune mediated complication after
      thrombolysis with streptokinase for acute anterior wall myocardial infarction: a
      caution to be vigilant.
AB  - Guillain-Barre syndrome (GBS) constitutes a heterogeneous group of immune
      mediated peripheral neuropathic disorders that can be triggered by a variety of
      antecedent events. Clinical symptoms are thought to result from streptokinase
      antibody-mediated damage to the local blood-nerve barrier. We report the case of
      a 50-year-old man with acute anterior wall myocardial infarction who developed
      GBS as a manifestation of autoimmune hypersensitivity reaction to the drug 17
      days after thrombolytic therapy with streptokinase. The patient was treated with
      a 5-day course of intravenous gamma globulin and his symptoms improved and there
      was no residual deficit. The case forms a reminder of the autoimmune
      complications of non-fibrin specific agents that can sometimes be catastrophic
      and require persistent and vigilant in-hospital and immediate postdischarge
      follow-up and immediate management. 

PMID- 24099762
TI  - Facial plexiform neurofibroma: is it truly just skin deep?
AB  - A middle-aged Chinese woman presented with a slowly enlarging mass over the right
      side of her face that was later proven histologically to be a plexiform
      neurofibroma. This was associated with a localised depression over her right
      temple. There were no other features of neurofibromatosis-1. The presentation and
      biological behaviour of plexiform neurofibromas are reviewed in this manuscript.
      Particular attention is paid to the interaction of plexiform neurofibromas with
      their surrounding structures, as well as the postulated mechanisms by which this
      occurs. 

PMID- 24099763
TI  - Orthokeratinised odontogenic cyst mimicking periapical cyst.
AB  - Orthokeratinised odontogenic cyst (OOC) denotes the odontogenic cyst that
      microscopically has an orthokeratinised epithelial lining. OOC is characterised
      by a less-aggressive behaviour and a low rate of recurrence. This report
      describes a case of OOC involving posterior part of the mandible that mimicked
      periapical cyst in a 14-year-old boy. The initial clinical diagnosis was given as
      periapical cyst based on the clinical and radiographical features. Enucleation of
      the cyst was performed and the specimen was sent for histopathological
      examination. A definite diagnosis of OOC was made by histopathological
      examination of the biopsy specimen. This case emphases on including OOC in the
      differential diagnosis of radiolucencies occurring in the periapical region of
      non-vital tooth. 

PMID- 24099764
TI  - Declining vision: saved by a tracheostomy.
AB  - A 37-year-old woman presented to our hospital with a history of headaches,
      blurred vision and declining visual acuity. She had a history of obstructive
      sleep apnoea associated with Treacher Collins syndrome, a rare congenital
      disorder characterised by craniofacial deformities and obstruction of the upper
      airways. On funduscopy we noted bilateral papilloedema and retinal haemorrhages.
      A CT scan of the brain excluded a space occupying lesion and contrast-enhanced CT
      did not show evidence of venous sinus thrombosis. The cerebrospinal fluid opening
      pressure on lumbar puncture was normal. We made a diagnosis of visual loss and
      papilloedema secondary to chronic CO2 retention from obstructive sleep apnoea.
      Her vision and headaches improved remarkably following a permanent tracheostomy.
      This case highlights the association between obstructive sleep apnoea and
      papilloedema and shows that the associated visual loss can ultimately be restored
      with a tracheostomy. 

PMID- 24099765
TI  - Functional analysis of the NH2-terminal hydrophobic region and BRICHOS domain of
      GKN1.
AB  - Gastrokine 1 (GKN1) protects the gastric antral mucosa and promotes healing by
      facilitating restitution and proliferation after injury. GKN1 is down-regulated
      in Helicobacter pylori-infected gastric epithelial cells and loss of GKN1
      expression is tightly associated with gastric carcinogenesis. However, the
      underlying mechanisms as a tumor suppressor are largely unknown. Presently, the
      hydrophobic region and BRICHOS domain of GKN1, pGKN1(D13N), pGKN1(Delta68-199),
      and pGKN1(Delta1-67,165-199) were shown to suppress gastric cancer cell growth
      and recapitulate GKN1 functions. As well, the hydrophobic region and BRICHOS
      domain of GKN1 had a synergistic anti-cancer effect with 5-FU on tumor cell
      growth, implying that the NH2-terminal hydrophobic region and BRICHOS domain of
      GKN1 are sufficient for tumor suppression, thereby suggesting a therapeutic
      intervention for gastric cancer. Also, its domain inducing endogenous miR-185
      directly targeted the epigenetic effectors DNMT1 and EZH2 in gastric cancer
      cells. Our results suggest that the NH2-terminal hydrophobic region and BRICHOS
      domain of GKN1 are sufficient for its tumor suppressor activities.

PMID- 24099766
TI  - NOD2 triggers PGE2 synthesis leading to IL-8 activation in Staphylococcus aureus
      infected human conjunctival epithelial cells.
AB  - We previously showed that Staphylococcus aureus and Pseudomonas aeruginosa
      stimulate IL-8 expression in human conjunctival epithelial cells through
      different signal transduction pathways. As in some cell types both the bacteria
      may induce the release of prostaglandin E2 (PGE2) and PGE2 may affect the
      expression of IL-8, we aimed at investigating whether in human conjunctival cells
      infected with S. aureus or P. aeruginosa the activation of IL-8 transcription was
      mediated by PGE2 and which were the underlying molecular mechanisms. We found
      that S. aureus, but not P. aeruginosa, triggered IL-8 activation by increasing
      COX-2 expression and PGE2 levels in a time-dependent manner. Overexpression of
      nucleotide-binding oligomerization domain-2 (NOD2) resulted to be essential in
      the enhancement of IL-8 induced by S. aureus. It dramatically activated c-jun NH2
      terminal kinase (JNK) pathway which in turn led to COX2 upregulation and
      ultimately to IL-8 transcription. The full understanding of the S. aureus-induced
      biochemical processes in human conjunctival epithelium will bring new insight to
      the knowledge of the molecular mechanisms involved in conjunctiva bacterial
      infections and develop novel treatment aiming at phlogosis modulation.

PMID- 24099767
TI  - Acceleration of bone development and regeneration through the Wnt/beta-catenin
      signaling pathway in mice heterozygously deficient for GSK-3beta.
AB  - Glycogen synthase kinase (GSK)-3beta plays an important role in
      osteoblastogenesis by regulating the Wnt/beta-catenin signaling pathway.
      Therefore, we investigated whether GSK-3beta deficiency affects bone development
      and regeneration using mice heterozygously deficient for GSK-3beta (GSK-3beta(+/
      )). The amounts of beta-catenin, c-Myc, cyclin D1, and runt-related transcription
      factor-2 (Runx2) in the bone marrow cells of GSK-3beta(+/-) mice were
      significantly increased compared with those of wild-type mice, indicating that
      Wnt/beta-catenin signals were enhanced in GSK-3beta(+/-) mice. Microcomputed
      tomography of the distal femoral metaphyses demonstrated that the volumes of both
      the cortical and trabecular bones were increased in GSK-3beta(+/-) mice compared
      with those in wild-type mice. Subsequently, to investigate the effect of GSK
      3beta deficiency on bone regeneration, we established a partial bone defect in
      the femur and observed new bone at 14 days after surgery. The volume and mineral
      density of the new bone were significantly higher in GSK-3beta(+/-) mice than
      those in wild-type mice. These results suggest that bone formation and
      regeneration in vivo are accelerated by inhibition of GSK-3beta, probably through
      activation of the Wnt/beta-catenin signaling pathway.

PMID- 24099768
TI  - MiR-92b regulates the cell growth, cisplatin chemosensitivity of A549 non small
      cell lung cancer cell line and target PTEN.
AB  - MicroRNAs (miRNAs) have emerged to play important roles in tumorigenesis and drug
      resistance of human cancer. Fewer studies were explored the roles of miR-92b on
      human lung cancer cell growth and resistance to cisplatin (CDDP). In this paper,
      we utilized real-time PCR to verify miR-92b was significantly up-regulated in non
      small cell lung cancer (NSCLC) tissues compared to matched adjacent normal
      tissues. In vitro assay demonstrated that knock-down of miR-92b inhabits cell
      growth and sensitized the A549/CDDP cells to CDDP. Furthermore, we found miR-92b
      could directly target PTEN, a unique tumor suppressor gene, which was
      downregulated in lung cancer tissues compared to the matched adjacent normal
      tissues. These data indicate that the miR-92b play an oncogene roles by regulates
      cell growth, cisplatin chemosensitivity phenotype, and could serve as a novel
      potential maker for NSCLC therapy. 

PMID- 24099769
TI  - Abnormal spermatogenesis and reduced fertility in transgenic mice expressing the
      immediate-early protein IE180 of pseudorabies virus.
AB  - Transcription factors of alphaherpesviruses not only control the expression of
      their own viral genes, but also influence the gene expression of mammalian cells.
      In the course of breeding of the transgenic mouse line (TgIE96) expressing the
      immediate-early protein IE180 of pseudorabies virus belonging to the subfamily
      Alphaherpesvirinae, we found that TgIE96 male mice suffered from severe breeding
      difficulties. Testes of TgIE96 were smaller than that of non-transgenic
      littermates and abnormal spermatogenesis such as morphological, numerical and
      functional anomalies of spermatozoa were found in the transgenic mouse line.
      Expression of IE180 was detected in the germ cells at all stages, especially
      spermatocytes, and fewer Sertoli cells. In addition, expression of IE180 was also
      detected in the germinal cells of C57BL/6 mice inoculated with PRV into their
      testes. These results suggest that IE180 of PRV induces male infertility by
      abnormal spermatogenesis, which effect morphological, numerical, and functional
      anomalies of spermatozoa, in transgenic mice. 

PMID- 24099770
TI  - Regulation of autophagy and apoptosis in response to angiotensin II in HL-1
      cardiomyocytes.
AB  - BACKGROUND: Autophagy and apoptosis are two important regulators of cell
      survival, and are often observed simultaneously in response to noxious stimuli.
      Anoxia is a known stimulus for autophagy and apoptosis, and angiotensin (Ang) II
      is a major mediator of anoxic injury. However, specific responses to anoxia and
      Ang II in terms of occurrence of autophagy and apoptosis have still not been
      delineated. METHODS AND RESULTS: We observed that autophagy (measured as LC3
      staining, and Beclin-1 and p62 Western blotting) was an early response and
      apoptosis (measured as TUNEL staining, and Annexin V and Smac/Diablo Western
      blotting) became dominant as the duration of anoxia was prolonged. Autophagy also
      occurred quickly in response to low concentrations of Ang II. When exposed to
      high concentrations of Ang II, a significant number of cells developed apoptosis,
      while autophagy response decreased. Ang II-mediated apoptosis was blocked by Ang
      II type 1 receptor (AT1R) blocker losartan as well as by the AT2R blocker
      PD123319. Ang II-induced autophagy was blocked by losartan, but not by PD123319.
      CONCLUSION: Exposure to Ang II, a mediator of anoxic injury, initiates a rapid
      autophagy response, perhaps in an attempt to protect tissues from the impending
      noxious effects. However, when anoxia (and thereby release of Ang II) is
      prolonged, the process of apoptosis dominates. These processes will determine the
      outcome of cardiomyocyte well-being in states of hypoxia.

PMID- 24099771
TI  - Modulation of adipogenesis, lipolysis and glucose consumption in 3T3-L1
      adipocytes and C2C12 myotubes by hydroxytyrosol acetate: a comparative study.
AB  - Hydroxytyrosol acetate (Hd-Ac) is a polyphenol that is present in the olive fruit
      and oil at a concentration similar to that of hydroxytyrosol (Hd). The effects of
      Hd-Ac on adipogenesis, lipolysis, and glucose consumption in 3T3-L1 cells were
      investigated. Treatment with Hd-Ac at concentrations of 0-75 MUmol/L inhibited
      3T3-L1 differentiation and lipid accumulation in a dose-dependent manner. At the
      same concentration range, no effect on cell viability was observed in the MTT
      assay. Inhibition of adipogenesis was associated with the downregulation of
      PPARgamma, C/EBPalpha, SREBP-1c, and their downstream target genes (GLUT4, CD36,
      and FAS) as revealed by qRT-PCR. On the other hand, Hd-Ac dose dependently
      activated glycerol release in fully differentiated 3T3-L1 adipocytes, indicating
      lipolysis. This stimulation of lipolysis was mediated via the activation of
      hormone-sensitive lipase (HSL) by phosphorylation at Ser563 and Ser660, and the
      phosphorylation of perilipin. Further investigation of the in vitro activities of
      this polyphenol showed that Hd-Ac has the capability to increase glucose
      consumption in 3T3-L1 adipocytes and C2C12 myotubes.

PMID- 24099772
TI  - Mesenchymal stem cells from osteoporotic patients feature impaired signal
      transduction but sustained osteoinduction in response to BMP-2 stimulation.
AB  - Osteoporotic fractures show reduced callus formation and delayed bone healing.
      Cellular sources of fracture healing are mesenchymal stem cells (MSC) that
      differentiate into osteoblasts by stimulation with osteoinductive cytokines, such
      as BMP-2. We hypothesized that impaired signal transduction and reduced
      osteogenic differentiation capacity in response to BMP-2 may underlie the delayed
      fracture healing. Therefore, MSC were isolated from femoral heads of healthy and
      osteoporotic patients. Grouping was carried out by bone mineral densitometry in
      an age-matched manner. MSC were stimulated with BMP-2. Signal transduction was
      assessed by western blotting of pSMAD1/5/8 and pERK1/2 as well as by quantitative
      RT-PCR of Runx-2, Dlx5, and Osteocalcin. Osteogenic differentiation was assessed
      by quantifying Alizarin Red staining. Osteoporotic MSC featured an accurate
      phosphorylation pattern of SMAD1/5/8 but a significantly reduced activation of
      ERK1/2 by BMP-2 stimulation. Furthermore, osteoporotic MSC showed significantly
      reduced basal expression levels of Runx-2 and Dlx5. However, Runx-2, Dlx5, and
      Osteocalcin expression showed adequate up-regulation due to BMP-2 stimulation.
      The global osteogenic differentiation in standard osteogenic differentiation
      media was reduced in osteoporotic MSC. Nevertheless, osteoporotic MSC were shown
      to feature an adequate induction of osteogenic differentiation due to BMP-2
      stimulation. Taken together, we here demonstrate osteoporosis associated
      alterations in BMP-2 signaling but sustained specific osteogenic differentiation
      capacity in response to BMP-2. Therefore, BMP-2 may represent a promising
      therapeutic agent for the treatment of fractures in osteoporotic patients. 

PMID- 24099773
TI  - The Groucho protein Grg4 suppresses Smad7 to activate BMP signaling.
AB  - Groucho related genes encode transcriptional repressor proteins critical for
      normal developmental processes. The bone morphogenetic proteins belong to the
      transforming growth factor-beta (TGF-beta) superfamily and play important
      signaling roles in development and disease. However, the regulation of BMP
      signaling, especially within cells, is largely unknown. In this report, we show
      that expression of the Groucho related gene Grg4 robustly activates the
      expression of a BMP reporter gene, as well as enhancing and sustaining the
      upregulation of the endogenous Id1 gene induced by BMP7. BMP7 administration did
      not affect the endogenous level of Grg4 nor did it enhance the phosphorylation of
      receptor activated Smad proteins. Rather, Grg4 expression reduced the levels of
      the endogenous inhibitory Smad7, thus increasing the transcriptional responses
      mediated by BMP responsive sequences. The data point to a novel mechanisms for
      attenuating BMP signaling through altering the ratio of activating versus
      inhibitory Smad proteins. 

PMID- 24099774
TI  - Specific inhibition of hepatitis C virus entry into host hepatocytes by fungi
      derived sulochrin and its derivatives.
AB  - Hepatitis C virus (HCV) is a major causative agent of hepatocellular carcinoma.
      Although various classes of anti-HCV agents have been under clinical development,
      most of these agents target RNA replication in the HCV life cycle. To achieve a
      more effective multidrug treatment, the development of new, less expensive anti
      HCV agents that target a different step in the HCV life cycle is needed. We
      prepared an in-house natural product library consisting of compounds derived from
      fungal strains isolated from seaweeds, mosses, and other plants. A cell-based
      functional screening of the library identified sulochrin as a compound that
      decreased HCV infectivity in a multi-round HCV infection assay. Sulochrin
      inhibited HCV infection in a dose-dependent manner without any apparent
      cytotoxicity up to 50 MUM. HCV pseudoparticle and trans-complemented particle
      assays suggested that this compound inhibited the entry step in the HCV life
      cycle. Sulochrin showed anti-HCV activities to multiple HCV genotypes 1a, 1b, and
      2a. Co-treatment of sulochrin with interferon or a protease inhibitor telaprevir
      synergistically augmented their anti-HCV effects. Derivative analysis revealed
      anti-HCV compounds with higher potencies (IC50<5 MUM). This is the first report
      showing an antiviral activity of methoxybenzoate derivatives. Thus, sulochrin
      derivatives are anti-HCV lead compounds with a new mode of action.

PMID- 24099775
TI  - Homeobox A7 stimulates breast cancer cell proliferation by up-regulating estrogen
      receptor-alpha.
AB  - Breast cancer is the most common hormone-dependent malignancy in women. Homeobox
      (HOX) transcription factors regulate many cellular functions, including cell
      migration, proliferation and differentiation. The aberrant expression of HOX
      genes has been reported to be associated with human reproductive cancers.
      Estradiol (E2) and its nuclear receptors, estrogen receptor (ER)-alpha and ER
      beta, are known to play critical roles in the regulation of breast cancer cell
      growth. However, an understanding of the potential relationship between HOXA7 and
      ER in breast cancer cells is limited. In this study, our results demonstrate that
      knockdown of HOXA7 in MCF7 cells significantly decreased cell proliferation and
      ERalpha expression. In addition, HOXA7 knockdown attenuated E2-induced cell
      proliferation as well as progesterone receptor (PR) expression. The stimulatory
      effects of E2 on cell proliferation and PR expression were abolished by co
      treatment with ICI 182780, a selective ERalpha antagonist. In contrast,
      overexpression of HOXA7 significantly stimulated cell proliferation and ERalpha
      expression. Moreover, E2-induced cell proliferation, as well as PR expression,
      was enhanced by the overexpression of HOXA7. Neither knockdown nor overexpression
      of HOXA7 affected the ER-beta levels. Our results demonstrate a novel mechanistic
      role for HOXA7 in modulating breast cancer cell proliferation via regulation of
      ERalpha expression. This finding contributes to our understanding of the role
      HOXA7 plays in regulating the proliferation of ER-positive cancer cells. 

PMID- 24099776
TI  - The (R)-enantiomer of CE3F4 is a preferential inhibitor of human exchange protein
      directly activated by cyclic AMP isoform 1 (Epac1).
AB  - Isoform 1 and isoform 2 of exchange protein directly activated by cAMP (Epac1 and
      Epac2) contribute to cAMP signaling in numerous cellular processes. Their guanine
      nucleotide exchange factor (GEF) activity toward the small GTP-binding protein
      Rap1 is stimulated by the agonist cAMP. CE3F4, a tetrahydroquinoline analog,
      prevents Epac1 activation in vitro and in living cultured cells by inhibiting the
      GEF activity of Epac1. However, the activity of the (R)- and (S)-enantiomers of
      CE3F4, as well as the ability of CE3F4 and its analogs to inhibit Epac2 GEF
      activity, have not yet been investigated. In this study, we report that (R)-CE3F4
      is a more potent cAMP antagonist than racemic CE3F4 and (S)-CE3F4, inhibiting the
      GEF activity of Epac1 with 10-times more efficiency than (S)-CE3F4. Epac2, in
      contrast to Epac1, is activated more efficiently by cAMP than by 8-(4
      chlorophenylthio)-2'-O-methyladenosine-3',5'-cyclic monophosphate (007), an Epac
      selective cAMP analog. (R)-CE3F4 displays Epac isoform preference, with 10-fold
      selectivity for Epac1 over Epac2. Deletion of the N-terminal cyclic nucleotide
      binding domain of Epac2 does not affect the characteristics of activation of
      Epac2 by cAMP and by 007, nor its inhibition by CE3F4. Finally, the evaluation of
      a series of CE3F4 structural analogs as GEF inhibitors allowed identifying
      structural features that are important for high Epac1 inhibitory activity of
      CE3F4. We conclude that the (R)-enantiomer of CE3F4 is a preferential inhibitor
      of Epac1 with high potency in the low micromolar range, and we suggest that this
      compound may be a useful pharmacological tool for investigating the functional
      role of Epac1 in cAMP signaling. 

PMID- 24099777
TI  - A novel link between Slc22a18 and fat accumulation revealed by a mutation in the
      spontaneously hypertensive rat.
AB  - Two different strains of the spontaneously hypertensive rat (SHR) exist, either
      with or without a Cd36 mutation. In the F2 population derived from a cross
      between these two SHR strains, the mutant Cd36 allele was tightly linked to
      differences in metabolic phenotypes but not to those in fat pad weight. This
      suggested the existence of another crucial mutation related to adiposity. Linkage
      analysis of this F2 population showed a significant linkage between the rat
      chromosome 1 region (D1Rat240-D1Wox28) and fat pad weight. By integrating both
      positional and expression information, we identified a donor splice site mutation
      in the gene for solute carrier family 22 member 18 (Slc22a18) in SHR with reduced
      fat pad weight. This mutation was located at the linkage peak with a maximum
      logarithm of odds score of 7.7 and caused skipping of the whole exon 9 that
      results in a complete loss of a whole membrane-spanning region of the rat
      Slc22a18 protein. Slc22a18 mRNA was abundantly expressed in isolated adipocytes
      and in a differentiation-dependent manner in 3T3-L1 cells. Knockdown of the
      Slc22a18 mRNA via infection of adenoviral vectors markedly inhibited both
      triglyceride accumulation and adipocyte differentiation in 3T3-L1 cells. By
      contrast, overexpression of the Slc22a18 mRNA had the opposite effects. These
      results reveal a novel link between Slc22a18 and fat accumulation and suggest
      that this gene could be a new therapeutic target in obesity. 

PMID- 24099778
TI  - [Aorto-oesophageal and aorto-bronchial fistulae secondary to endovascular repair
      of a thoracic aortic aneurysm].

PMID- 24099779
TI  - Central venous catheter care for the patients with cancer: ultrasound-guided
      insertion should be strongly recommended for internal jugular vein
      catheterization.

PMID- 24099780
TI  - Advanced chondrosarcomas: role of chemotherapy and survival.
AB  - BACKGROUND: There are limited data about the role of chemotherapy in patients
      with advanced chondrosarcomas. METHODS: The medical charts of 180 patients with
      advanced chondrosarcomas having received chemotherapy in 15 participating
      institutions between 1988 and 2011 were reviewed. RESULTS: Median age was 52
      years. Sixty-three percent of patients had conventional chondrosarcoma and 88%
      had metastatic disease. Combination chemotherapy was delivered in 98 cases
      (54.5%). One hundred and thirty-one patients (73%) received an anthracycline
      containing regimen. Using RECIST, the objective response rate was significantly
      different according to histological subtype, being 31% for mesenchymal
      chondrosarcoma, 20.5% for dedifferentiated chondrosarcoma, 11.5% for conventional
      chondrosarcoma and 0% for clear-cell chondrosarcoma (P = 0.04). Median
      progression-free survival (PFS) was 4.7 months [95% confidence interval (CI) 3
      6.5]. Performance status (PS) >=2, number of metastatic sites >=1 and single
      agent regimen were independently associated with poor PFS. Median overall
      survival (OS) was 18 months (95% CI 14.5-21.6). PS, number of metastatic sites
      and palliative surgery were independently associated with OS. CONCLUSIONS:
      Conventional chemotherapy have very limited efficacy in patients with advanced
      chondrosarcoma, the highest benefit being observed in mesenchymal and
      dedifferentiated chondrosarcoma. These data should be used as a reference for
      response and outcome in the assessment of investigational drugs in advanced
      chondrosarcoma.

PMID- 24099781
TI  - Experimental study and modeling of the influence of mixed electrolytes on
      adsorption of macromolecules on a hydrophobic resin.
AB  - The influence of mixed electrolytes on the adsorption of macromolecules on a
      hydrophobic resin is explored. The macromolecules are native lysozyme, di-PEG
      lysozyme-5kDa and pure PEG-6kDa, the adsorbent is Toyopearl PPG-600M, a mildly
      hydrophobic resin. The solvent is a 25 mM aqueous sodium phosphate buffer at pH
      7.0 containing additional salts with an overall ionic strength of 3000 mM. The
      studied salts are sodium chloride, ammonium sulfate, sodium sulfate and ammonium
      chloride. Both pure salts as well as binary and ternary mixtures of these salts
      with varying ratios of the amounts of the salts are studied. For all solvents
      adsorption equilibrium isotherms are measured at 25 degrees C. Mixing
      electrolytes can lead to synergetic effects, i.e. the adsorption in the mixed
      electrolyte system is sometimes distinctly larger than expected from the results
      of the single electrolyte systems. The single ions, not the salts, drive the
      adsorption. A mathematical model is developed, which describes the influence of
      the different ions and their cross-interactions on the studied adsorption
      process.

PMID- 24099782
TI  - Analytical model for out-of-field dose in photon craniospinal irradiation.
AB  - The prediction of late effects after radiotherapy in organs outside a treatment
      field requires accurate estimations of out-of-field dose. However, out-of-field
      dose is not calculated accurately by commercial treatment planning systems
      (TPSs). The purpose of this study was to develop and test an analytical model for
      out-of-field dose during craniospinal irradiation (CSI) from photon beams
      produced by a linear accelerator. In two separate evaluations of the model, we
      measured absorbed dose for a 6 MV CSI using thermoluminescent dosimeters placed
      throughout an anthropomorphic phantom and fit the measured data to an analytical
      model of absorbed dose versus distance outside of the composite field edge. These
      measurements were performed in two separate clinics-the University of Texas MD
      Anderson Cancer Center (MD Anderson) and the American University of Beirut
      Medical Center (AUBMC)-using the same phantom but different linear accelerators
      and TPSs commissioned for patient treatments. The measurement at AUBMC also
      included in-field locations. Measured dose values were compared to those
      predicted by TPSs and parameters were fit to the model in each setting. In each
      clinic, 95% of the measured data were contained within a factor of 0.2 and one
      root mean square deviation of the model-based values. The root mean square
      deviations of the mathematical model were 0.91 cGy Gy(-1) and 1.67 cGy Gy(-1) in
      the MD Anderson and AUBMC clinics, respectively. The TPS predictions agreed
      poorly with measurements in regions of sharp dose gradient, e.g., near the field
      edge. At distances greater than 1 cm from the field edge, the TPS underestimated
      the dose by an average of 14% +/- 24% and 44% +/- 19% in the MD Anderson and
      AUBMC clinics, respectively. The in-field measured dose values of the measurement
      at AUBMC matched the dose values calculated by the TPS to within 2%. Dose
      algorithms in TPSs systematically underestimated the actual out-of-field dose.
      Therefore, it is important to use an improved model based on measurements when
      estimating out-of-field dose. The model proposed in this study performed well for
      this purpose in two clinics and may be applicable in other clinics with similar
      treatment field configurations. 

PMID- 24099783
TI  - The contribution of heavy metals in cigarette smoke condensate to malignant
      transformation of breast epithelial cells and in vivo initiation of neoplasia
      through induction of a PI3K-AKT-NFkappaB cascade.
AB  - Cigarette smoking is a crucial factor in the development and progression of
      multiple cancers including breast. Here, we report that repeated exposure to a
      fixed, low dose of cigarette smoke condensate (CSC) prepared from Indian
      cigarettes is capable of transforming normal breast epithelial cells, MCF-10A,
      and delineate the biochemical basis for cellular transformation. CSC transformed
      cells (MCF-10A-Tr) were capable of anchorage-independent growth, and their
      anchorage dependent growth and colony forming ability were higher compared to the
      non-transformed MCF-10A cells. Increased expression of biomarkers representative
      of oncogenic transformation (NRP-1, Nectin-4), and anti-apoptotic markers (PI3K,
      AKT, NFkappaB) were also noted in the MCF-10A-Tr cells. Short tandem repeat (STR)
      profiling of MCF-10A and MCF-10A-Tr cells revealed that transformed cells
      acquired allelic variation during transformation, and had become genetically
      distinct. MCF-10A-Tr cells formed solid tumors when implanted into the mammary
      fat pads of Balb/c mice. Data revealed that CSC contained approximately 1.011MUg
      Cd per cigarette equivalent, and Cd (0.0003MUg Cd/1*10(7) cells) was also
      detected in the lysates from MCF-10A cells treated with 25MUg/mL CSC. In similar
      manner to CSC, CdCl2 treatment in MCF-10A cells caused anchorage independent
      colony growth, higher expression of oncogenic proteins and increased PI3K-AKT
      NFkappaB protein expression. An increase in the expression of PI3K-AKT-NFkappaB
      was also noted in the mice xenografts. Interestingly, it was noted that CSC and
      CdCl2 treatment in MCF-10A cells increased ROS. Collectively, results suggest
      that heavy metals present in cigarettes of Indian origin may substantially
      contribute to tumorigenesis by inducing intercellular ROS accumulation and
      increased expression of PI3K, AKT and NFkappaB proteins. 

PMID- 24099785
TI  - Nardilysin, ADAM10, and Alzheimer's disease: of mice and men.

PMID- 24099784
TI  - Blood lead level association with lower body weight in NHANES 1999-2006.
AB  - BACKGROUND: Lead exposure is associated with low birth-weight. The objective of
      this study is to determine whether lead exposure is associated with lower body
      weight in children, adolescents and adults. METHODS: We analyzed data from NHANES
      1999-2006 for participants aged >=3 using multiple logistic and multivariate
      linear regression. Using age- and sex-standardized BMI Z-scores, overweight and
      obese children (ages 3-19) were classified by BMI >=85 th and >=95 th
      percentiles, respectively. The adult population (age >=20) was classified as
      overweight and obese with BMI measures of 25-29.9 and >=30, respectively. Blood
      lead level (BLL) was categorized by weighted quartiles. RESULTS: Multivariate
      linear regressions revealed a lower BMI Z-score in children and adolescents when
      the highest lead quartile was compared to the lowest lead quartile (beta (SE)=
      0.33 (0.07), p<0.001), and a decreased BMI in adults (beta (SE)=-2.58 (0.25),
      p<0.001). Multiple logistic analyses in children and adolescents found a negative
      association between BLL and the percentage of obese and overweight with BLL in
      the highest quartile compared to the lowest quartile (OR=0.42, 95% CI: 0.30-0.59;
      and OR=0.67, 95% CI: 0.52-0.88, respectively). Adults in the highest lead
      quartile were less likely to be obese (OR=0.42, 95% CI: 0.35-0.50) compared to
      those in the lowest lead quartile. Further analyses with blood lead as restricted
      cubic splines, confirmed the dose-relationship between blood lead and body weight
      outcomes. CONCLUSIONS: BLLs are associated with lower body mass index and obesity
      in children, adolescents and adults.

PMID- 24099786
TI  - Impaired empathic abilities and reduced white matter integrity in schizophrenia.
AB  - Empathic abilities are impaired in schizophrenia. Although the pathology of
      schizophrenia is thought to involve disrupted white matter integrity, the
      relationship between empathic disabilities and altered white matter in the
      disorder remains unclear. The present study tested associations between empathic
      disabilities and white matter integrity in order to investigate the neural basis
      of impaired empathy in schizophrenia. Sixty-nine patients with schizophrenia and
      69 age-, gender-, handedness-, education- and IQ level-matched healthy controls
      underwent diffusion-weighted imaging. Empathic abilities were assessed using the
      Interpersonal Reactivity Index (IRI). Using tract-based spatial statistics
      (TBSS), the associations between empathic abilities and white matter fractional
      anisotropy (FA), a measure of white matter integrity, were examined in the
      patient group within brain areas that showed a significant FA reduction compared
      with the controls. The patients with schizophrenia reported lower perspective
      taking and higher personal distress according to the IRI. The patients showed a
      significant FA reduction in bilateral deep white matter in the frontal, temporal,
      parietal and occipital lobes, a large portion of the corpus callosum, and the
      corona radiata. In schizophrenia patients, fantasy subscales positively
      correlated with FA in the left inferior fronto-occipital fasciculi and anterior
      thalamic radiation, and personal distress subscales negatively correlated with FA
      in the splenium of the corpus callosum. These results suggest that disrupted
      white matter integrity in these regions constitutes a pathology underpinning
      specific components of empathic disabilities in schizophrenia, highlighting that
      different aspects of empathic impairments in the disorder would have, at least
      partially, distinct neuropathological bases. 

PMID- 24099787
TI  - Portal vein thrombosis after partial splenic embolization in liver cirrhosis:
      efficacy of anticoagulation and long-term follow-up.
AB  - PURPOSE: To investigate the treatment and long-term outcome of portal vein
      thrombosis (PVT) after partial splenic embolization (PSE). MATERIALS AND METHODS:
      From January 2006 to December 2011, 145 patients with hypersplenism caused by
      cirrhotic portal hypertension underwent PSE. In 11 cases, PVT was detected 13-42
      days after PSE. Among the 11 patients, 5 underwent anticoagulant therapy because
      of clinical symptoms, and 6 did not receive anticoagulation because they were
      symptom-free (4 patients) or experienced variceal bleeding (2 patients). The long
      term follow-up data from these 11 patients were analyzed retrospectively.
      RESULTS: The 11 patients with PVT had a mean splenic infarction ratio of 71.5%.
      The mean duration of follow-up was 37.6 months. During the follow-up period, none
      of the 5 patients who underwent anticoagulation developed variceal hemorrhage
      despite presenting with large esophagogastric varices. Four of the five patients
      achieved complete resolution of thrombosis, and one did not develop thrombus
      progression. However, among the 6 patients who did not undergo anticoagulation, 2
      developed esophagogastric variceal hemorrhage secondary to thrombus progression,
      3 developed cavernous transformation of the portal vein and variceal progression,
      and 1 had partial calcification of the thrombus. Two patients who had variceal
      bleeding or rebleeding underwent a transjugular intrahepatic portosystemic shunt.
      Complete recanalization of the portal vein was achieved after the procedures.
      CONCLUSIONS: PVT is a severe, potentially fatal complication of PSE. Early
      detection of PVT and prompt anticoagulation are effective to avoid serious
      consequences of PVT.

PMID- 24099788
TI  - Response to letter to the editor: 'cause of death and correlation with autopsy
      findings in burns patients'.

PMID- 24099789
TI  - Irradiated burn.

PMID- 24099790
TI  - An approach to 'use of split-thickness plantar skin grafts in the treatment of
      hyperpigmented skin-grafted fingers and palms in previously burned patients'.

PMID- 24099791
TI  - Surface and hysteresis properties of lipid interphases composed by head group
      substituted phosphatidylethanolamines.
AB  - This work analyzes the surface properties of PE-containing membranes modified at
      the head group region by the addition of methyl and ethyl residues at or near the
      amine group. These residues alter the lipid-lipid and lipid-water interactions by
      changes in the hydrogen bonding capability and the charge density of the amine
      group thus affecting the electrostatic interaction. The results obtained by
      measuring the dipole potential, the zeta potential, the area per lipid and the
      compressibility properties allow to conclude that the H-bonding capability
      prevails in the lipid-lipid interaction. The non polar groups attached to the C2
      carbon of the ethanolamine chain introduces a steric hindrance against
      compression and increases the dipole potential. The analysis of areas suggests
      that lipids with methylated head groups have a much larger compressibility at
      expense of the elimination of hydration water, which is congruent with the
      broader extent of the hysteresis loop. 

PMID- 24099792
TI  - Equivalent functions for B7.1 and B7.2 costimulation in mediating host resistance
      to Mycobacterium tuberculosis.
AB  - B7.1 and B7.2 are homologous costimulatory molecules expressed predominantly on
      antigen-presenting cells (APC). Interaction of these B7 molecules with CD28 and
      CTLA-4 expressed on T cells is a critical step in T cell activation. Previously,
      we reported that Mycobacterium tuberculosis infection in the combined absence of
      B7.1 and B7.2 resulted in impaired host resistance to the pathogen. Despite their
      structural similarities, the individual contribution of B7.1 and B7.2 to the
      development of pathogenic T cells in autoimmune diseases and protective T cells
      in infectious diseases is markedly distinct. In the current study, we therefore
      examined whether B7.1 and B7.2 have discrete, equivalent, or overlapping
      functions in mediating host resistance to M. tuberculosis. We found that the
      individual absence of either B7.1 or B7.2 had no effect on the ability of the
      host to contain bacterial load in the lungs, recruit immune cells to the lung,
      generate a Th1 response, or induce a pulmonary granulomatous response. These
      results indicate that B7.1 and B7.2 molecules have equal ability to mediate host
      resistance to M. tuberculosis, underscoring the therapeutic utility of individual
      B7.1 and B7.2 antagonists in treating inflammatory disorders. 

PMID- 24099793
TI  - Inhibitory effects of a cationic liposome on allergic reaction mediated by mast
      cell activation.
AB  - Several studies have shown that cationic liposomes exert immunomodulatory effects
      with low immunogenicity and toxicity, and offer advantages such as easy
      preparation and targeting. Cationic liposomes not only transport DNA to immune
      cells but also enhance the function of antigen presenting cells such as dendritic
      cells and macrophages. Here, we investigated the effect of a particular cationic
      liposome on mast cell function during allergic reaction. We found that the
      cationic liposomes bound to the mast cell surface suppressed degranulation
      induced by cross-linking of high affinity immunoglobulin E receptors in a time-
      and dose-dependent manner. The suppression of degranulation was mediated by
      impairment of the sustained level of intracellular Ca(2+) concentration
      ([Ca(2+)]i) derived from the inhibition of store-operated Ca(2+) entry. The
      decrease in sustained elevation of [Ca(2+)]i led to the suppression of
      phosphorylation of soluble N-ethylmaleimide-sensitive factor attachment protein
      receptor proteins such as SNAP-23, syntaxin-4, which are necessary for membrane
      fusion between secretory granules and the plasma membrane during degranulation.
      Furthermore, the cationic liposomes suppressed vascular permeability elevation
      induced by mast cell activation in mice. These results showed that cationic
      liposomes possess the novel property of inhibiting mast cell activation,
      suggesting the possibility of developing cationic liposomes as anti-allergic
      effectors. 

PMID- 24099794
TI  - Novel compound 1,3-bis (3,5-dichlorophenyl) urea inhibits lung cancer
      progression.
AB  - The successful clinical management of lung cancer is limited by frequent loss-of
      function mutations in p53 which cooperates with chronic oxidant-stress induced
      adaptations in mercapturic acid pathway (MAP) which in turn regulates critical
      intracellular signaling cascades that determine therapeutic refractoriness.
      Hence, we investigated the anti-cancer effects and mechanisms of action of a
      novel compound called 1,3-bis(3,5-dichlorophenyl) urea (COH-SR4) in lung cancer.
      Treatment with COH-SR4 effectively inhibited the survival and clonogenic
      potential along with inducing apoptosis in lung cancer cells. COH-SR4 treatment
      caused the inhibition of GST activity and G0/G1 cell cycle arrest and inhibited
      the expression of cell cycle regulatory proteins CDK2, CDK4, cyclin A, cyclin B1,
      cyclin E1, and p27. The COH-SR4 activated AMPK pathway and knock-down of AMPK
      partially reversed the cytotoxic effects of COH-SR4 in lung cancer. COH-SR4
      treatment lead to regression of established xenografts of H358 lung cancer cells
      without any overt toxicity. The histopathology of resected tumor sections
      revealed an increase in pAMPK, a decrease in the nuclear proliferative marker
      Ki67 and angiogenesis marker CD31. Western-blot analyses of resected tumor
      lysates revealed a decrease in pAkt and anti-apoptotic protein Bcl2 along with an
      increase in pAMPK, pro-apoptotic protein Bax and cleaved PARP levels.
      Importantly, COH-SR4 lead to decrease in the mesenchymal marker vimentin and
      increase in the normal epithelial marker E-cadherin. The results from our in
      vitro and in-vivo studies reveal that COH-SR4 represents a novel candidate with
      strong mechanistic relevance to target aggressive and drug-resistant lung tumors.

PMID- 24099795
TI  - Reevesioside F induces potent and efficient anti-proliferative and apoptotic
      activities through Na+/K+-ATPase alpha3 subunit-involved mitochondrial stress and
      amplification of caspase cascades.
AB  - Reevesioside F, isolated from Reevesia formosana, induced anti-proliferative
      activity that was highly correlated with the expression of Na+/K+-ATPase alpha3
      subunit in several cell lines, including human leukemia HL-60 and Jurkat cells,
      and some other cell lines. Knockdown of alpha3 subunit significantly inhibited
      cell apoptosis suggesting a crucial role of the alpha3 subunit. Reevesioside F
      induced a rapid down-regulation of survivin protein, followed by release of
      cytochrome c from mitochondria and loss of mitochondrial membrane potential
      (DeltaPsim). Further examination demonstrated the mitochondrial damage in
      leukemic cells through Mcl-1 down-regulation, Noxa up-regulation and an increase
      of the formation of truncated Bid, tBim and a 23-kDa cleaved Bcl-2 fragment.
      Furthermore, reevesioside F induced an increase of mitochondria-associated acetyl
      alpha-tubulin that may also contribute to apoptosis. The caspase cascade was
      profoundly activated by reevesioside F. Notably, the specific caspase-3 inhibitor
      z-DEVD-fmk significantly blunted reevesioside F-induced loss of DeltaPsim and
      apoptosis, suggesting that caspase-3 activation may further amplify mitochondrial
      damage and apoptotic signaling cascade. In spite of being a cardiac glycoside,
      reevesioside F did not increase the intracellular Ca2+ levels. Moreover, CGP
      37157 which blocked Na+/Ca2+ exchanger on plasma membrane and mitochondria did
      not modify reevesioside F-mediated effect. In summary, the data suggest that
      reevesioside F induces apoptosis through the down-regulation of survivin and Mcl
      1, and the formation of pro-apoptotic fragments from Bcl-2 family members. The
      loss of DeltaPsim and mitochondrial damage are responsible for the activation of
      caspases. Moreover, the amplification of caspase-3-mediated signaling pathway
      contributes largely to the execution of apoptosis in leukemic cells.

PMID- 24099796
TI  - A novel binuclear palladacycle complex inhibits melanoma growth in vitro and in
      vivo through apoptosis and autophagy.
AB  - Malignant melanoma is an aggressive skin cancer and it is reported to be the most
      treatment-resistant human cancer. Here we describe the anti-tumour activity of a
      novel binuclear palladacycle complex (AJ-5) in vertical growth phase (ME1402) and
      metastatic (WM1158) melanoma cell lines. We show that compared to normal control
      cell lines, AJ-5 is more effective in inhibiting the proliferation of ME1402 and
      WM1158 melanoma cells with IC50 values of 0.19 and 0.20MUM, respectively. Flow
      cytometry analyses showed that AJ-5 induced apoptosis (sub-G1 peak) which was
      confirmed by Annexin V-FITC/propidium iodide double-staining, nuclear
      fragmentation and an increase in the levels of PARP cleavage. Furthermore, AJ-5
      was shown to induce both intrinsic and extrinsic apoptotic pathways as measured
      by PUMA, Bax and active caspases. Interestingly, AJ-5 treatment also
      simultaneously induced the formation of autophagosomes and led to an increase in
      the autophagy markers LC3II and Beclin1. Inhibition of autophagy reduced AJ-5
      cytotoxicity suggesting that AJ-5 induced autophagy was a cell death and not cell
      survival mechanism. Moreover we show that AJ-5 induces the ATM-CHK2 DNA damage
      pathway and that its anti-tumour function is mediated by the p38 and ERK1/2
      signalling pathways. Importantly, AJ-5 treatment efficiently reduced tumour
      growth in melanoma bearing mice and induced high levels of autophagy and
      apoptosis markers. Together these findings suggest that AJ-5 may be an effective
      chemotherapeutic drug in the treatment of melanoma, a highly aggressive and
      intractable cancer. 

PMID- 24099798
TI  - The contribution of motor commands to position sense differs between elbow and
      wrist.
AB  - Recent studies have suggested that centrally generated motor commands contribute
      to the perception of position and movement at the wrist, but not at the elbow.
      Because the wrist and elbow experiments used different methods, this study was
      designed to resolve the discrepancy. Two methods were used to test both the elbow
      and wrist (20 subjects each). For the wrist, subjects sat with their right arm
      strapped to a device that restricted movement to the wrist. Before each test,
      voluntary contraction of wrist flexor or extensor muscles controlled for muscle
      spindle thixotropy. After relaxation, the wrist was moved to a test angle.
      Position was indicated either with a pointer, or by matching with the
      contralateral wrist, under two conditions: when the reference wrist was relaxed
      or when its muscles were contracted isometrically (30% maximum). The elbow
      experiment used the same design to measure position sense in the passive elbow
      and with elbow muscles contracting (30% maximum). At the wrist when using a
      pointer, muscle contraction altered significantly the perceived wrist angle in
      the direction of contraction by 7 deg [3 deg, 12 deg] (mean [95% confidence
      interval]) with a flexor contraction and 8 deg [4 deg, 12 deg] with an extensor
      contraction. Similarly, in the wrist matching task, there was a change of 13 deg
      [9 deg, 16 deg] with a flexor contraction and 4 deg [1 deg, 8 deg] with an
      extensor contraction. In contrast, contraction of elbow flexors or extensors did
      not alter significantly the perceived position of the elbow, compared with rest.
      The contribution of central commands to position sense differs between the elbow
      and the wrist.

PMID- 24099797
TI  - Estrogen, vascular estrogen receptor and hormone therapy in postmenopausal
      vascular disease.
AB  - Cardiovascular disease (CVD) is less common in premenopausal women than men of
      the same age or postmenopausal women, suggesting vascular benefits of estrogen.
      Estrogen activates estrogen receptors ERalpha, ERbeta and GPR30 in endothelium
      and vascular smooth muscle (VSM), which trigger downstream signaling pathways and
      lead to genomic and non-genomic vascular effects such as vasodilation, decreased
      VSM contraction and growth and reduced vascular remodeling. However, randomized
      clinical trials (RCTs), such as the Women's Health Initiative (WHI) and Heart and
      Estrogen/progestin Replacement Study (HERS), have shown little vascular benefits
      and even adverse events with menopausal hormone therapy (MHT), likely due to
      factors related to the MHT used, ER profile, and RCT design. Some MHT forms,
      dose, combinations or route of administration may have inadequate vascular
      effects. Age-related changes in ER amount, distribution, integrity and post-ER
      signaling could alter the vascular response to MHT. The subject's age,
      preexisting CVD, and hormone environment could also reduce the effects of MHT.
      Further evaluation of natural and synthetic estrogens, phytoestrogens, and
      selective estrogen-receptor modulators (SERMs), and the design of appropriate MHT
      combinations, dose, route and 'timing' could improve the effectiveness of
      conventional MHT and provide alternative therapies in the peri-menopausal period.
      Targeting ER using specific ER agonists, localized MHT delivery, and activation
      of specific post-ER signaling pathways could counter age-related changes in ER.
      Examination of the hormone environment and conditions associated with hormone
      imbalance such as polycystic ovary syndrome may reveal the causes of abnormal
      hormone-receptor interactions. Consideration of these factors in new RCTs such as
      the Kronos Early Estrogen Prevention Study (KEEPS) could enhance the vascular
      benefits of estrogen in postmenopausal CVD. 

PMID- 24099799
TI  - Identification of unique release kinetics of serotonin from guinea-pig and human
      enterochromaffin cells.
AB  - The major source of serotonin (5-HT) in the body is the enterochromaffin (EC)
      cells lining the intestinal mucosa of the gastrointestinal tract. Despite the
      fact that EC cells synthesise ~95% of total body 5-HT, and that this 5-HT has
      important paracrine and endocrine roles, no studies have investigated the
      mechanisms of 5-HT release from single primary EC cells. We have developed a
      rapid primary culture of guinea-pig and human EC cells, allowing analysis of
      single EC cell function using electrophysiology, electrochemistry, Ca(2+)
      imaging, immunocytochemistry and 3D modelling. Ca(2+) enters EC cells upon
      stimulation and triggers quantal 5-HT release via L-type Ca(2+) channels. Real
      time amperometric techniques reveal that EC cells release 5-HT at rest and this
      release increases upon stimulation. Surprisingly for an endocrine cell storing 5
      HT in large dense core vesicles (LDCVs), EC cells release 70 times less 5-HT per
      fusion event than catecholamine released from similarly sized LDCVs in endocrine
      chromaffin cells, and the vesicle release kinetics instead resembles that
      observed in mammalian synapses. Furthermore, we measured EC cell density along
      the gastrointestinal tract to create three-dimensional (3D) simulations of 5-HT
      diffusion using the minimal number of variables required to understand the
      physiological relevance of single cell 5-HT release in the whole-tissue milieu.
      These models indicate that local 5-HT levels are likely to be maintained around
      the activation threshold for mucosal 5-HT receptors and that this is dependent
      upon stimulation and location within the gastrointestinal tract. This is the
      first study demonstrating single cell 5-HT release in primary EC cells. The mode
      of 5-HT release may represent a unique mode of exocytosis amongst endocrine cells
      and is functionally relevant to gastrointestinal sensory and motor function.

PMID- 24099800
TI  - A single point mutation reveals gating of the human ClC-5 Cl-/H+ antiporter.
AB  - ClC-5 is a 2Cl(-)/1H(+) antiporter highly expressed in endosomes of proximal
      tubule cells. It is essential for endocytosis and mutations in ClC-5 cause Dent's
      disease, potentially leading to renal failure. However, the physiological role of
      ClC-5 is still unclear. One of the main issues is whether the strong
      rectification of ClC-5 currents observed in heterologous systems, with currents
      elicited only at positive voltages, is preserved in vivo and what is the origin
      of this rectification. In this work we identified a ClC-5 mutation, D76H, which,
      besides the typical outward currents of the wild-type (WT), shows inward tail
      currents at negative potentials that allow the estimation of the reversal of ClC
      5 currents for the first time. A detailed analysis of the dependence of these
      inward tail currents on internal and external pH and [Cl(-)] shows that they are
      generated by a coupled transport of Cl(-) and H(+) with a 2 : 1 stoichiometry.
      From this result we conclude that the inward tail currents are caused by a gating
      mechanism that regulates ClC-5 transport activity and not by a major alteration
      of the transport mechanism itself. This implies that the strong rectification of
      the currents of WT ClC-5 is at least in part caused by a gating mechanism that
      activates the transporter at positive potentials. These results elucidate the
      biophysical properties of ClC-5 and contribute to the understanding of its
      physiological role.

PMID- 24099801
TI  - Development of heart failure is independent of K+ channel-interacting protein 2
      expression.
AB  - Abnormal ventricular repolarization in ion channelopathies and heart disease is a
      major cause of ventricular arrhythmias and sudden cardiac death. K(+) channel
      interacting protein 2 (KChIP2) expression is significantly reduced in human heart
      failure (HF), contributing to a loss of the transient outward K(+) current (Ito).
      We aim to investigate the possible significance of a changed KChIP2 expression on
      the development of HF and proarrhythmia. Transverse aortic constrictions (TAC)
      and sham operations were performed in wild-type (WT) and KChIP2(-/-) mice.
      Echocardiography was performed before and every 2 weeks after the operation. Ten
      weeks post-surgery, surface ECG was recorded and we paced the heart in vivo to
      induce arrhythmias. Afterwards, tissue from the left ventricle was used for
      immunoblotting. Time courses of HF development were comparable in TAC-operated WT
      and KChIP2(-/-) mice. Ventricular protein expression of KChIP2 was reduced by 70%
      after 10 weeks TAC in WT mice. The amplitudes of the J and T waves were enlarged
      in KChIP2(-/-) control mice. Ventricular effective refractory period, RR, QRS and
      QT intervals were longer in mice with HF compared to sham-operated mice of either
      genotype. Pacing-induced ventricular tachycardia (VT) was observed in 5/10 sham
      operated WT mice compared with 2/10 HF WT mice with HF. Interestingly, and
      contrary to previously published data, sham-operated KChIP2(-/-) mice were
      resistant to pacing-induced VT resulting in only 1/10 inducible mice. KChIP2(-/-)
      with HF mice had similar low vulnerability to inducible VT (1/9). Our results
      suggest that although KChIP2 is downregulated in HF, it is not orchestrating the
      development of HF. Moreover, KChIP2 affects ventricular repolarization and lowers
      arrhythmia susceptibility. Hence, downregulation of KChIP2 expression in HF may
      be antiarrhythmic in mice via reduction of the fast transient outward K(+)
      current.

PMID- 24099803
TI  - Identification of protective immunogens from extracellular secretome of
      Edwardsiella tarda.
AB  - Edwardsiella tarda is an opportunistic pathogen that causes a great loss in
      aquaculture. Identification of immune protective immunogens is a key step for
      development of subunit vaccines and control of the infectious diseases caused by
      the bacterium. This study aims to identify the protective antigens from
      extracellular secretory proteome of E. tarda. Out of 38 extracellular secretory
      proteins predicted by PSORTb, 20 genes were randomly cloned and their recombinant
      proteins were expressed in Escherichia coli BL21 and purified by either affinity
      chromatography or inclusion body washing. The purified recombinant proteins were
      used for investigation of immune protection in zebrafish model using active
      immunization approach. Half of them had significant immune protection compared
      with the control. Out of them, four, EseC, ETAE_2088, FlgD and ETAE_2130, showed
      approximately 60% relative percent survivals as a result of the highly protective
      antigens identified. Except for FlgD, the other three were first reported here.
      Moreover, the present study identified EseC and ETAE_2088 in bacterial
      extracellular fraction. These results indicate that secretory proteome is an
      interesting pool used for identification of immune protective antigens, and the
      four highly protective antigens identified provide useful candidates for
      development of subunit vaccines.

PMID- 24099802
TI  - Modulation of stimulus-specific adaptation by GABA(A) receptor activation or
      blockade in the medial geniculate body of the anaesthetized rat.
AB  - Stimulus-specific adaptation (SSA), which describes adaptation to repeated sounds
      concurrent with the maintenance of responsiveness to uncommon ones, may be an
      important neuronal mechanism for the detection of and attendance to rare stimuli
      or for the detection of deviance. It is well known that GABAergic
      neurotransmission regulates several different response properties in central
      auditory system neurons and that GABA is the major inhibitory neurotransmitter
      acting in the medial geniculate body (MGB). The mechanisms underlying SSA are
      still poorly understood; therefore, the primary aim of the present study was to
      examine what role, if any, MGB GABAergic circuits play in the generation and/or
      modulation of SSA. Microiontophoretic activation of GABA(A) receptors (GABA(A)Rs)
      with GABA or with the selective GABA(A)R agonist gaboxadol significantly
      increased SSA (computed with the common SSA index, CSI) by decreasing responses
      to common stimuli while having a lesser effect on responses to novel stimuli. In
      contrast, GABA(A)R blockade using gabazine resulted in a significant decrease in
      SSA. In all cases, decreases in the CSI during gabazine application were
      accompanied by an increase in firing rate to the stimulus paradigm. The present
      findings, in conjunction with those of previous studies, suggest that GABA(A)
      mediated inhibition does not generate the SSA response, but can regulate the
      level of SSA sensitivity in a gain control manner. The existence of successive
      hierarchical levels of processing through the auditory system suggests that the
      GABAergic circuits act to enhance mechanisms to reduce redundant information.

PMID- 24099805
TI  - A history of fish vaccination: science-based disease prevention in aquaculture.
AB  - Disease prevention and control are crucial in order to maintain a sustainable
      aquaculture, both economically and environmentally. Prophylactic measures based
      on stimulation of the immune system of the fish have been an effective measure
      for achieving this goal. Immunoprophylaxis has become an important part in the
      successful development of the fish-farming industry. The first vaccine for
      aquaculture, a vaccine for prevention of yersiniosis in salmonid fish, was
      licensed in USA in 1976. Since then the use of vaccines has expanded to new
      countries and new species simultaneous with the growth of the aquaculture
      industry. This paper gives an overview of the achievements in fish vaccinology
      with particular emphasis on immunoprophylaxis as a practical tool for a
      successful development of bioproduction of aquatic animals. 

PMID- 24099806
TI  - Automatic 3D ultrasound calibration for image guided therapy using intramodality
      image registration.
AB  - Many real time ultrasound (US) guided therapies can benefit from management of
      motion-induced anatomical changes with respect to a previously acquired
      computerized anatomy model. Spatial calibration is a prerequisite to transforming
      US image information to the reference frame of the anatomy model. We present a
      new method for calibrating 3D US volumes using intramodality image registration,
      derived from the 'hand-eye' calibration technique. The method is fully automated
      by implementing data rejection based on sensor displacements, automatic
      registration over overlapping image regions, and a self-consistency error metric
      evaluated continuously during calibration. We also present a novel method for
      validating US calibrations based on measurement of physical phantom displacements
      within US images. Both calibration and validation can be performed on arbitrary
      phantoms. Results indicate that normalized mutual information and localized cross
      correlation produce the most accurate 3D US registrations for calibration.
      Volumetric image alignment is more accurate and reproducible than point selection
      for validating the calibrations, yielding <1.5 mm root mean square error, a
      significant improvement relative to previously reported hand-eye US calibration
      results. Comparison of two different phantoms for calibration and for validation
      revealed significant differences for validation (p = 0.003) but not for
      calibration (p = 0.795). 

PMID- 24099808
TI  - [Estimation of risk factors of progression of placental dysfunction in women with
      recurrent pregnancy loss in past medical history, using retrospective,
      comparative and statistical analysis].
AB  - The retrospective comparative analysis of the following three groups is
      presented: control group composed of 100 somatically healthy pregnant women; 592
      pregnant women with recurrent pregnancy loss complicated with placental
      dysfunction in the past medical history - the 1st group; and 592 pregnant women
      with recurrent pregnancy loss without placental dysfunction in the past medical
      history - the 2nd group. The fetal cardiotocography was analyzed with
      determination of non-stress test, fetus ultrasound investigation; the fetus
      biophysical profile was determined; the fates of the current pregnancy and
      childbearing and the state of the newborn infant were studied; using the
      statistical analysis, the risk factors affecting the progression of placental
      dysfunction in women with recurrent pregnancy loss in the past medical history
      were discovered. 

PMID- 24099804
TI  - The mucosal immune system of fish: the evolution of tolerating commensals while
      fighting pathogens.
AB  - The field of mucosal immunology research has grown fast over the past few years,
      and our understanding on how mucosal surfaces respond to complex antigenic
      cocktails is expanding tremendously. With the advent of new molecular sequencing
      techniques, it is easier to understand how the immune system of vertebrates is,
      to a great extent, orchestrated by the complex microbial communities that live in
      symbiosis with their hosts. The commensal microbiota is now seen as the "extended
      self" by many scientists. Similarly, fish immunologist are devoting important
      research efforts to the field of mucosal immunity and commensals. Recent
      breakthroughs on our understanding of mucosal immune responses in teleost fish
      open up the potential of teleosts as animal research models for the study of
      human mucosal diseases. Additionally, this new knowledge places immunologists in
      a better position to specifically target the fish mucosal immune system while
      rationally designing mucosal vaccines and other immunotherapies. In this review,
      an updated view on how teleost skin, gills and gut immune cells and molecules,
      function in response to pathogens and commensals is provided. Finally, some of
      the future avenues that the field of fish mucosal immunity may follow in the next
      years are highlighted. 

PMID- 24099809
TI  - Functional state of red blood system as a possible predictor of individual
      radiosensitivity and carcinogenesis.
AB  - Functional state of the red blood system is being studied in patients with
      adenoma and carcinoma of thyroid gland. The aim of this study was to determine
      the possible predictors of the individual radiosensitivity and the probability of
      developing cancer on the basis of the comparable characteristic of functional
      state of the red blood system in patients with adenoma and carcinoma of thyroid
      gland. Functional state of the red blood system is being studied in patients with
      adenoma and carcinoma of thyroid gland. The functional state of RBC was
      determined by using the specially developed method based on analysis of the
      dynamics of peripheral blood erythrocytes distribution according to their
      spherulation degree (Q) and volume (V). Spherulation degree is considered as
      biological age and along with the volume determines the probability of their
      elimination from circulating bed. In connection with these positions distribution
      P=P(V,Q) express mechanism of production-aging-elimination of RBC of peripheral
      blood in circulating conditions and according to their dynamics we can discuss
      about the character of these processes. Revelation of differences certainly
      indicates high heterogeneity by the quality of young fractions of RBC of
      peripheral blood in patients with cancer versus the patients with adenoma. This
      parameter may be determined as a marker of individual radiosensitivity and
      probability of developing cancer. However the issue about haemopoesis instability
      in patients with cancer, whether it is caused by genotype, phenotype or toxic
      action of products of disintegration of tumors, demands the further researches. 

PMID- 24099807
TI  - Lexical activation during sentence comprehension in adolescents with history of
      Specific Language Impairment.
AB  - One remarkable characteristic of speech comprehension in typically developing
      (TD) children and adults is the speed with which the listener can integrate
      information across multiple lexical items to anticipate upcoming referents.
      Although children with Specific Language Impairment (SLI) show lexical deficits
      (Sheng & McGregor, 2010) and slower speed of processing (Leonard et al., 2007),
      relatively little is known about how these deficits manifest in real-time
      sentence comprehension. In this study, we examine lexical activation in the
      comprehension of simple transitive sentences in adolescents with a history of SLI
      and age-matched, TD peers. Participants listened to sentences that consisted of
      the form, Article-Agent-Action-Article-Theme, (e.g., The pirate chases the ship)
      while viewing pictures of four objects that varied in their relationship to the
      Agent and Action of the sentence (e.g., Target, Agent-Related, Action-Related,
      and Unrelated). Adolescents with SLI were as fast as their TD peers to fixate on
      the sentence's final item (the Target) but differed in their post-action onset
      visual fixations to the Action-Related item. Additional exploratory analyses of
      the spatial distribution of their visual fixations revealed that the SLI group
      had a qualitatively different pattern of fixations to object images than did the
      control group. The findings indicate that adolescents with SLI integrate lexical
      information across words to anticipate likely or expected meanings with the same
      relative fluency and speed as do their TD peers. However, the failure of the SLI
      group to show increased fixations to Action-Related items after the onset of the
      action suggests lexical integration deficits that result in failure to consider
      alternate sentence interpretations. LEARNING OUTCOMES: As a result of this paper,
      the reader will be able to describe several benefits of using eye-tracking
      methods to study populations with language disorders. They should also recognize
      several potential explanations for lexical deficits in SLI, including possible
      reduced speed of processing, and degraded lexical representations. Finally, they
      should recall the main outcomes of this study, including that adolescents with
      SLI show different timing and location of eye-fixations while interpreting
      sentences than their age-matched peers.

PMID- 24099810
TI  - [Prophylaxis and treatment of periimpalntitis].
AB  - Ultrasonic Vector System (Durr Dental, Germany) is the best means for complex
      treatment of peri-implantitis. The therapeutic effect of the system proved anti
      inflammatory and regenerative impact of calcium hydroxyapatite on the soft tissue
      around the implant. The effectiveness of the result provided full, persistent and
      safe removal of bacteria, dental plaque, infected granulation tissue; the
      possibility of regular monitoring, prevention of re-infection of pathological
      pockets, without damaging the hard and soft tissues around the implant, the
      implant itself and artificial fragile crown, securing superb cleaning and
      polishing of the implant surface, which is an important condition for the further
      reduction and inactivation of pathogenic bacteria population. Healing peri
      implantitis pockets at the expense of using conventional oral hygiene is not
      possible. Tools of carbon fiber in combination with a suspension Vector Fluid
      Polish and the Vector machine successfully accomplish the function of
      disinfection and polishing. The aim of the research was to present the results of
      peri-implantitis treatment with a new ultrasonic device Ultrasonic Vector System.
      Surgical treatment (21% of patients) was atraumatic. The risk of infection was
      decreased and necessary conditions were created for a significant acceleration of
      the tissue healing process. Relying on the successful results we recommend Vector
      therapy before surgical procedures. Complex treatment was repeated depending on
      the clinical manifestations of inflammation around the implant. To prevent peri
      implantitis, and get timely diagnosis of unwanted changes, and to maintain
      implants and the soft tissues around them in a healthy condition, the patients
      were strongly recommended to visit the dentist 3-4 times a year. They were
      offered professional oral hygiene and accessible parts of the implants with the
      help of a Vector machine. Relying on the results of the research we conducted
      during the treatment of peri-implantitis, we have seen the "magic" efficiency and
      the need to apply the "Vector" system into the complex treatment of this disease.

PMID- 24099811
TI  - [Biomechanical basis splinting of loose teeth while preserving their mobility at
      physiological].
AB  - The aim of this study was biomechanical rationale for splinting mobile teeth with
      periodontitis according to the height and slope of teeth crowns, their degree of
      mobility, and type of occlusion. The research studied the effect of axial
      vertical and horizontal loads on the functioning of the proposed method of
      splinting. Set clear indications and contraindications for the use of the method
      of splinting. Biomechanically proven unreasonableness includes teeth with III
      degree of mobility in the splinted construction. Clinical variant of splinting is
      only possible at the height of the anatomical crowns of the teeth of at least 7
      mm, otherwise the preferred laboratory methods for the manufacture of tires. 

PMID- 24099812
TI  - Cytokines and T regulatory cells in the pathogenesis of type 1 diabetes.
AB  - Type 1 diabetes (T1D) is an inflammatory disease of the pancreatic islet, in
      which insulin-producing beta-cells are preferentially destroyed to varying
      degrees by the concerted action of autoreactive T-cells and monocytic cells. Th1
      type cytokines (IL-2 and IFN-gamma) correlate with T1D, whereas Th2 (IL-4 and IL
      10), Th3 (TGF-beta), and T regulatory cell-type cytokines (IL-10 and TGF-beta)
      correlate with protection from T1D. An altered balance between the
      proinflammatory and regulatory T-cell responses, in which T regulatory cells lose
      the battle, leads to T1D. The aim of current study was to determine the role of
      CD4+CD25+ regulatory T cells and cytokines: IFN-gamma, IL-6, TNF-alpha, IL-10, IL
      4, IL-17 in pathogenesis of T1D.The study was carried out on 71 patients
      suffering from T1D at the department of endocrinology, Tbilisi State Medical
      University and Diabetic Children Association. The circulating levels of (IFN
      gamma, IL-6, TNF-alpha, IL-10, IL-4, IL-17) were determined by ELISA according
      manufactures' protocol (R&D Systems Inc., USA). Tregs - CD4+CD25+ frequency was
      determined on cytofluorometer (BD FACSCalibur flow cytometer, USA). Statistical
      analysis was performed by using STATISTICA 8.0 for PC (Statsoft Inc.,
      Minneapolis, USA) and Mann-Whitney U-test. Our study revealed significant
      decrease of IL-6, TNF-alpha, IL-10 and IL-4 plasma levels (1.197-, 1.188-, 1.504-
      and 1.840-times respectively) and increase of IL-17 plasma level (2.311-times) on
      the background of almost unchanged frequency of Tregs in patients with type 1
      diabetes. In T1D patients CD4+CD25+ Tregs frequency did not correlate with
      diabetes duration and positivly correlated with age and IL-4. We supposed that
      decreased level of IL-4 and IL-10 reflects inhibited functional activity of these
      cells. We suggested that shifted balance of Th17/Tregs towards inflammatory IL-17
      producing cells and decreased levels of suppressive cytokines IL-4 and IL-10 play
      crucial role in T1D. Future studies are needed to clarify changes in which
      subsets of heterogenous population of regulatory cells are associated with
      diabetes duration and how the therapy affects their frequency and function. 

PMID- 24099813
TI  - Management of acute Achilles tendinopathy: effect of etoricoxib on pain control
      and leg stiffness.
AB  - Tendinopathies are a major cause of disability in the athletic population; the
      main purpose of the treatment of these injuries is to reduce pain and improve
      function promptly. The objective of this randomized, active comparator
      controlled, blinded study was to evaluate etoricoxib efficacy in pain control and
      leg stiffness in athletes suffering acute unilateral Achilles tendinopathy. Fifty
      six eligible male athletes (mean age 37.5 +/- 11.0 y) suffering acute Achilles
      tendinopathy were randomized to receive either etoricoxib 120 mg oral once daily
      (n=28) or diclofenac 100 mg oral once daily (n=28). Pain (100-mm visual analogue
      scale-VAS), analgesic effect (percentage of 100-mm VAS reduction), satisfaction
      with pain management (PGART), and leg stiffness (LSR) were evaluated after one
      week of anti-inflammatory treatment. Over the 7-day treatment period, both
      etoricoxib and diclofenac provided significantly relief of Achilles tendon pain
      compared to that experienced at baseline (mean VAS 26.7 +/- 2.2 and 56.4 +/- 1.8,
      respectively; p<.001). Analgesic effect averaged 53.7 +/- 38.1% (etoricoxib=
      56.4% and diclofenac 50.6%, p=0.64). Patients referred high level of satisfaction
      with anti-inflammatory treatment (PGART = 2.0 +/- 1.3), while leg stiffness
      showed a significant improvement after one-week therapy (LSR 0.89 +/- 0.1 vs.
      0.95 +/- 0.1; p=0.038). PGART and LSR values within etoricoxib and diclofenac
      groups were not significant (p=0.46, and p=0.37, respectively). Both drugs were
      generally well tolerated; patients receiving etoricoxib reported significantly
      less side effects than those in the diclofenac group (0% and 14,2%, respectively,
      p=0.037). Etoricoxib is clinically effective in treatment of acute Achilles
      tendinopathy providing a magnitude of effect comparable to that of diclofenac
      with fewer side effects. Effective control of tendon pain in the acute phase of
      such sports-related injuries may be helpful to reduce morbidity and improve
      capabilities associated with high performance like leg stiffness.

PMID- 24099814
TI  - Distribution of cancer stem cells in ductal invasive carcinoma of breast
      (review).
AB  - Despite advances in detection and treatment of breast cancer, mortality from this
      disease remains high. According to contemporary point of view the reason for this
      lies in fact, that in addition to intertumor heterogeneity, there is also a high
      degree of intratumor diversity in cancer cell population. For most cancers it is
      less clear which cells within the tumor clone possess tumor-initiating cell
      function. During studying oncogenesis and maligniyaation processes a pool of
      cancer cells with stem characteristics - cancer stem cells (CSC) was identified.
      Indeed, the specifications of them let us conclude, that exactly these cells
      comprise the leading substrate for cancer initiation and self-renewal. Breast
      carcinomas have been reported to contain a subpopulation of CD44(+)/CD24(-)/low
      cancer cells, which are capable of generating tumors even when implanted in very
      low numbers. Exactly these cells are considered to be CSCs in different subtypes
      of breast cancer and cancers with CD44(+)/CD24(-)/low phenotype are confirmed to
      have a poor prognosis (but some controversies remain concerning this issue). The
      aim of the review was to assess the current literature published on the breast
      cancer stem cells. There are not so many studies, revealing the diversity of
      cancer stem cells in different types, different sizes and different grade of
      breast cancers. CSC distribution in breast cancer with lymph node involvement,
      metastasizing and chemoresistant cases, existence of circulating tumor cells in
      not studied precisely. So the concept of cancer stem cells in breast cancer is
      still a topic for discussions. This can bring light to a better understanding of
      the pathological process in breast cancer and ways to target it.

PMID- 24099815
TI  - Distribution of CD44/CD24 positive cells in ductal invasive carcinoma of breast
      of different grade and molecular subtype.
AB  - The purpose of our study was to learn the distribution characteristics of cancer
      stem cell markers (CD24, CD44) in invasive carcinomas with different grade and
      molecular subtype. For research was used 1324 postoperative breast cancer
      samples, from which were selected 393 patient with invasive ductal carcinoma
      samples examined 2008-2012 in Laboratory of "Pathgeo Union of Pathologist" is and
      N.Kipshidze Central University Hospital. The age range is between 23-73 year. For
      all cases were performed immunohistochemical study using ER, PR, Her2, Ki67, CK5-
      molecular markers (Leica Microsystems). For identify cancer stem cells
      mononuclear antibodies CD24 (BIOCARE MEDICAL, CD44 - Clone 156-3C11; CD24 - Clone
      SN3b) were used. Association of CD44/CD24 expression in different subtypes of
      cells, between clinicopathological parameters and different biological
      characteristics were performed by Pearson correlation and usind X2 tests.
      Obtained quantitative statistical analyses were performed by using SPSS V.19.0
      program. Statistically significant were considered 95% of confidence interval.
      The data shows, that towards G1-G3, amount of CD44 positive cases increased
      twice. CD44 positive cases are evenly distributed between Luminal A, Luminal B,
      HER2+, triple negative basal like cell subtypes and in significantly less (4,8
      times) in Her2+ cases. Maximum amount of CD44 negative cases is shown in Luminal
      A subtype, which could be possible cause of better prognosis and high sensitivity
      for chemotherapy. For one's part such aggressive subtypes of breast cancer as
      Luminal B and basal like cell type, are characterized by CD44 positive and
      antigen high expression, which can be reason of aggressive nature of this types
      and also reason of chemotherapy resistance. As well as amount of CD24 positive
      cases according to malignancy degree, also antigen expression features does not
      show any type of correlation between malignancy degree and CD24 positivity or
      with CD24 expression features, or presence of stem cells. That can be the reason
      of tumor aggressivity and chemoresistance. exceptions are Her2 positive tumors
      because they have different base of carcinogenesis. 

PMID- 24099816
TI  - The novel hypothesis of carcinogenesis and anti-cancer treatment perspectives -
      Hydroxyethylthiamine diphosphate.
AB  - In presented article, the novel hypothesis of carcinogenesis, and thorough
      discussion of some essential biochemical mechanisms which might be responsible
      for the malignant transformation of cells (bond disorders between Fe(3+) and S(+)
      methionine in cytochrome; blockage of the last 3-d orbital of Fe by the certain
      ligand and formation of 6th coordinated bond leading to Fe(3+) reduction up to
      Fe(2+) and cessation of tissue respiration; increase in mitochondrial pH and
      further in cell, leading to decreased activity of most of enzymes (thiamine
      diphosphate, oxidases); formation of S-adenosyl-methionine with its further
      dissociation and production of adenosine and homocysteine; effects of
      homocysteine on DNA structures, homocysteine-induced dimethylation of certain
      nitrogen basis and their extrusion from strands of DNA leading to mutations and
      cellular atypism) has been suggested. Along with theoretical discussions, article
      provides results of preliminary investigations carried out on C57Bl/6J mice with
      Ehrlich carcinoma aimed to capture lipoic acid amide with Hydroxyethylthiamine
      diphosphate, and study effects of Hydroxyethylthiamine diphosphate against
      malignant transformation of cells. Experiments have shown inhibition of cancer
      growth in treated animals. Morphological investigations of cancer tissue revealed
      necrotic zones, inflammatory infiltrations, central necrosis with adjacent
      inflammatory mono- and polymorph infiltrations, must cells, segmento-nuclear
      leukocytes, lymphadenoid follicular hyperplasia. According to the novel
      hypothesis of carcinogenesis and results of experiments the new approaches and
      perspectives of anti-cancer treatment with the use of Hydroxiethyl-thiamine
      diphosphate has been suggested.

PMID- 24099817
TI  - [Study of antioxidant activity of phenolic compounds from some species of
      Georgian flora].
AB  - The antioxidant activity of extracts obtained from different parts of Georgian
      flora species Hamamelis virginiana L., Astragalus caucasicus Pall., Astragalus
      microcephalus Willd., Vitis vinifera L., Rhododendron ponticum L., Rhododendron
      Ungernii Trautv., Ginkgo biloba L., Salvia officinalis L., Querqus iberica Stev.,
      Maclura aurantiaca Nutt., Cotinus coggygria Ledeb., Fraxinus ornus L., Urtica
      dioica L., Rhododendron caucasicum Pall., Pueraria hirsuta Matsum., Geranium
      pusillum L., Astragalus Tanae Sosn., Pinus silvestris L. has been studied.
      Comparison with ethylentetraacetate and alpha-tocopherole revealed high efficacy
      of all extracts studied. 45 individual phenolic compounds were isolated and
      described by chemical examination of biologically active objects. Common sage
      (Salvia officinalis) extract turned out as the most active (200 %). The chemical
      study revealed the dominant content of condensed tannins and low molecular
      phenolic compounds, which may be attributed to the high antioxidant activity.
      Biologically active antiatherosclerotic food additive "Salbin" was developed on
      the basis of Common sage - Salvia officinalis L. phenolic compounds. 

PMID- 24099818
TI  - Acanthosis nigricans in adolescents: a practical approach.
AB  - Acanthosis nigricans (AN) is a lesion affecting localized areas of the skin in
      persons with obesity and/or hyperinsulinemia. Biochemical mechanisms responsible
      for developing this hyperplastic lesion are unclear, but likely involve local
      cutaneous growth factors. It is associated with obesity, endocrinopathies
      (insulin resistance, diabetes mellitus, Cushing disease and acromegaly) and
      visceral malignancies. Clinicians should recognize AN because it may herald
      disorders ranging from endocrine disturbances to malignancy. Early recognition of
      these conditions is essential to identify children who are at highest risk for
      developing type 2 diabetes and further metabolic abnormalities. 

PMID- 24099819
TI  - Growth hormone deficiency in adults with thalassemia: an overview and the I-CET
      recommendations.
AB  - This review paper provides a summary of the current state of knowledge regarding
      GHD provides recommendations for the diagnosis and treatment of GHD in adult
      patients with thalassaemia major (TM). The reported prevalence of adult GHD and
      /or IGF-I deficiency in TM patients varies from 8% to 44 % in different centers.
      Because GH treatment requires analysis of many factors, including the effect of
      treatment on cardiac functions, metabolic parameters and psychosocial
      functioning, along with safety, ethical considerations, financial cost and other
      burdens of therapy, stringent diagnostic criteria are needed. The authors report
      the diagnostic recommendations of the International Study Group of Endocrine
      Complications in Thalassemia (I-CET) for adult TM patients.The pros and cons of
      GH treatment must be discussed with each patient, after which GH doses should be
      individualized and titrated to maximum efficacy with minimal side effects.
      Prospective studies to monitor potential benefits versus possible side-effects
      will enable endocrinologists to define recommendations on dosage and the long
      term effects, particularly on cardiovascular and bone status of GH therapy in
      adult TM patients. 

PMID- 24099820
TI  - High prevalence of central hypothyroidism in adult patients with beta-thalassemia
      major.
AB  - The commonest form of thyroid dysfunction seen in subjects with TM is primary
      hypothyroidism due to abnormalities of the thyroid gland. Central hypothyroidism
      (CH) has been reported as an uncommon clinical entity in TM patients although the
      anterior pituitary gland is particularly sensitive to free radical oxidative
      stresses. Diagnosis is usually made on a biochemical basis showing low
      circulating concentrations of thyroid hormone associated with an inappropriately
      low TSH levels. The diagnosis is not clinically obvious and a basal normal TSH
      level does not exclude the diagnosis of CH. Therefore, it is important that
      clinicians accurately interpret thyroid function tests. In TM patients, CH
      prevalence differs at different ages is unknown and it is not easy to diagnose
      because most of the symptoms of symptoms of CH are non specific and are
      frequently attributed to anaemia or other associated complications . We performed
      a cross-sectional analysis on a large database using the clinical records of our
      TM patients to explore the prevalence of CH in prepubertal (<11 years: 25
      patients; 13 males) peripubertal (between 11 and 16 years: 9 patients; 3 males),
      and pubertal TM subjects (>16 years: 305 patients; 164 males). Central
      hypothyroidism was present in 26 (7,6%) TM patients. Their mean age was 29.9 +/-
      8.4 years, 14 (53.8%) were males and 12 (46.1%) were females. The prevalence of
      CH was 6% in patients with a chronological age below 21 years and 7.9% in those
      above 21 years. Clinicians should be alert for the diagnosis of CH through
      accurate interpretation of thyroid function tests. We recommend L-thyroxine
      therapy if the level of FT4 is consistently low provided that the patient has
      normal cortisol levels.

PMID- 24099821
TI  - Athens University thalassemia expertise unit: evolution, structure, perspectives
      and patients' expectations.
AB  - Thalassemia Expertise Centres (TECs), were first organized in developed countries
      with high thalassemia prevalence in the 70's to meet the increasing demands of
      the implementation of frequent transfusions in the treatment of thalassemia, and
      to consequently adopt, the rapid advances in the management of the disease.
      Recent evaluation of longitudinal implementation of the national programs for
      prevention and treatment, demonstrated their efficacy for patients and public
      health. The beneficial effects focused on clinical symptoms amelioration,
      reduction of incidence and severity of complications and considerable improvement
      in survival, quality of life and social adaptation.National programs leaded to
      the modification of the most common genetic, fatal pediatric disease with short
      survival, to a chronic long-lived disease for adults and a very rare disease for
      children. In the few developed countries new perspectives for pediatric TECs need
      to be considered. 

PMID- 24099822
TI  - Health issues in adolescents' Internet use - benefits and risks.
AB  - The Internet has turned during the past decade into a major information resource
      in various domains of life and a communication venue among adolescents who seek
      health information via the net. The increasing availability of computers in
      homes, as well as wireless Internet access, means that adolescents today can go
      online anywhere, at any time. The media are not the leading cause of any major
      health problem, but they do contribute significantly to a variety of adolescent
      health problems, including aggressive behavior, sexual activity, drug use,
      obesity, sleep disorders, eating disorders, depression, suicide and self harm.
      This paper focuses on 3 major health issues in adolescents' Internet use: Body
      image and eating behaviors; sexuality and reproductive health behaviors; and self
      harm and suicidal behavior. This paper also demonstrates Internet venues where
      reliable health information is provided to young people by health professionals.
      Health professionals need to recognize the hazards of adolescents Internet use,
      and to address potential Internet abuse when encountering adolescents in clinical
      settings. 

PMID- 24099823
TI  - Immunologic pathomechanism of Hodgkin's lymphoma.
AB  - Hodgkin's lymphoma is a lymphoid malignancy of the immune system. The
      pathognomonic Hodgkin and Reed-Sternberg cells (HRS) are derived mainly from
      monoclonal, preapoptotic B cells, and they carry rearranged, somatically mutated
      immunoglobulin heavy chains. In an appropriate microenvironment, HRS cells escape
      from apoptosis by several mechanisms, including single mutations, aberrant
      signaling pathways. Eventually, weakened immune surveillance leads to
      uncontrolled, disproportional B cell proliferation. This review summarizes the
      latest findings on the pathogenesis of Hodgkin lymphoma, with a special emphasis
      on immunologic processes, and depicts current and future immunotherapeutic
      regimens, which improve treatment outcomes and reduce late toxicities. 

PMID- 24099824
TI  - Prediction of the energy required for extracorporeal shock wave lithotripsy of
      certain stones composition using simple radiology and computerized axial
      tomography.
AB  - OBJECTIVE: To demonstrate that urinary lithiasis have a specific susceptibility
      to fracture through extracorporeal shock wave lithotripsy (ESWL), which is common
      for all calculi with the same composition and which can be estimated before
      treatment using CT or plain x-ray. MATERIAL AND METHOD: We present an in vitro,
      prospective, randomized, blind and multi-centre study involving 308 urinary
      calculi. 193 of these met the inclusion criteria: whole calculi composed purely
      of calcium oxalate monohydrate (COM), uric acid (UA) or carbonate apatite (CA),
      or a mix of oxalate (COMix) and of a size greater than 0.5 cm. The samples were
      broken using lithotripsy until reaching a pre-established level of comminution.
      The variables employed were energy dose (Edose) per cm(3) of lithiasis and Edose
      adjusted to lithiasic surface (EdAJ) per cm(3). RESULTS: COM was the hardest,
      requiring an Edose of 119,624 mJ/cm(3) and an EdAJ of 36,983 mJ/cm(3), followed
      by COMix (75,501/36,983), CA (22,734/21,186) and UA (22,580/6,837) (P < .05).
      Gmax y Gmda were correlated with Edose (r = 0.434/r = 0.420) and EdAJ (r =
      0.599/r = 0.545) (P < .01). UH were correlated, in bone window and soft tissue
      window, with Edose/cm(3) (r = 0.478/r = 0.539) y EdAJ/cm(3) (r = 0.745/r = 0.758)
      (P < .01). CONCLUSIONS: In our in vitro research lithiasis require, due to the
      specific nature of their composition, a given amount of energy in order to be
      broken by ESWL, which is inherent to all those sharing the same composition, and
      can be predicted using CT or plain x-ray.

PMID- 24099825
TI  - Vesical schistosomiasis with terminal hematuria in sub-Saharan patients.
AB  - OBJECTIVES: To know the characteristics of vesical schistosomiasis caused by
      schistosoma hematobium in immigrant patients. MATERIAL AND METHODS: The
      retrospective study of 41 cases microbiologically diagnosed in our hospital over
      the last 16 years is presented. Data was collected on origin, age, presentation
      form, diagnostic tests and treatment. RESULTS: All were African patients whose
      ages ranged from 4 to 32 years and who had terminal macroscopic hematuria. Most
      of the patients (85%) were men. In all of the cases, diagnosis was by a urinary
      microbiological study and in one case, cystoscopy with a biopsy of a typical
      vesical lesion. Terminal hematuria is the most representative clinical sign. They
      were treated with praziquantel. CONCLUSIONS: The epidemiology and intermittent
      terminal hematuria in African patients should lead to the suspicion of vesical
      schistosomiasis as the first diagnostic option. Urinary microbiological study is
      a rapid, non-invasive, test with high diagnostic yield that would avoid
      performing invasive studies. Its simple treatment assures high level of
      compliance and consequent efficacy.

PMID- 24099826
TI  - Malignant mesothelioma of tunica vaginalis.

PMID- 24099827
TI  - Diagnostic and predictive value of urine PCA3 gene expression for the clinical
      management of patients with altered prostatic specific antigen.
AB  - OBJECTIVE: Analyze the impact of the introduction of the study of PCA3 gene in
      post-prostatic massage urine in the clinical management of patients with PSA
      altered, evaluating its diagnostic ability and predictive value of tumor
      aggressiveness. METHODS: Observational, prospective, multicenter study of
      patients with suspected prostate cancer (PC) candidates for biopsy. We present a
      series of 670 consecutive samples of urine collected post-prostatic massage for
      three years in which we determined the "PCA3 score" (s-PCA3). Biopsy was only
      indicated in cases with s-positive PCA3. RESULTS: The s-PCA3 was positive in
      43.7% of samples. In the 124 biopsies performed, the incidence of PC or atypical
      small acinar proliferation was 54%, reaching 68,6% in s-PCA3>=100. Statistically
      significant relationship between the s-PCA3 and tumor grade was demonstrated. In
      cases with s-PCA3 between 35 and 50 only 23% of PC were high grade (Gleason>=7),
      compared to 76.7% in cases with s-PCA3 over 50. There was a statistically
      significant correlation between s-PCA3 and cylinders affected. Both relationships
      were confirmed by applying a log-linear model. CONCLUSIONS: The incorporation of
      PCA3 can avoid the need for biopsies in 54% of patients. s-PCA3 positivity
      increases the likelihood of a positive biopsy, especially in higher s-PCA3 100
      (68.6%). s-PCA3 is also an indicator of tumor aggressiveness and provides
      essential information in making treatment decisions.

PMID- 24099828
TI  - Renal transplantation and polycystic: surgical considerations.
AB  - BACKGROUND: The indication and timing of nephrectomy in patients with autosomal
      dominant polycystic kidney disease (ADPKD) remain controversial, especially in
      patients who are candidates to renal transplantation (RT). The main surgical
      options such as unilateral vs. bilateral nephrectomy, nephrectomy before vs.
      after RT, or simultaneous nephrectomy and transplantation, are herein discussed.
      OBJECTIVE: Evidence acquisition of the best surgical management available for
      ADPKD in the context of kidney transplantation. ACQUISITION OF EVIDENCE:
      Systematic literature review in PubMed from 1978 to 2013 was conducted. Articles
      selected included:randomized controlled trials and cohort studies. Furthermore,
      well designed ADPKD reviews were considered for this study. SYNTHESIS OF
      EVIDENCE: Laparoscopic nephrectomy in ADPKD is a safe procedure with an
      acceptable complication rate. Unilateral nephrectomy has advantages over the
      bilateral one regarding the perioperative complication rate. Although the timing
      of nephrectomy is controversial, it seems that simultaneous nephrectomy and renal
      transplantation does not increase surgical morbidity neither affect graft
      survival. CONCLUSIONS: Simultaneous nephrectomy and RT appears to be an
      acceptable alternative to conventional two-stage procedure without any increased
      morbidity, in the context of ADPKD. Furthermore, laparoscopic nephrectomy
      performed in experienced centres is a safe alternative to conventional approach.

PMID- 24099829
TI  - The association between prehospital care and in-hospital treatment decisions in
      acute stroke: a cohort study.
AB  - BACKGROUND: Hospital prealerting in acute stroke improves the timeliness of
      subsequent treatment, but little is known about the impact of prehospital
      assessments on in-hospital care. OBJECTIVE: Examine the association between
      prehospital assessments and notification by emergency medical service staff on
      the subsequent acute stroke care pathway. METHODS: This was a cohort study of
      linked patient medical records. Consenting patients with a diagnosis of stroke
      were recruited from two urban hospitals. Data from patient medical records were
      extracted and entered into a Cox regression analysis to investigate the
      association between time to CT request and recording of onset time, stroke
      recognition (using the Face Arm Speech Test (FAST)) and sending of a prealert
      message. RESULTS: 151 patients (aged 71+/-15 years) travelled to hospital via
      ambulance and were eligible for this analysis. Time of symptom onset was recorded
      in 61 (40%) cases, the FAST test was positive in 114 (75%) and a prealert message
      was sent in 65 (44%). Following adjustment for confounding, patients who had time
      of onset recorded (HR 0.73, 95% CI 0.52 to 1.03), were FAST-positive (HR 0.54,
      95% CI 0.37 to 0.80) or were prealerted (HR 0.26, 95% CI 0.18 to 0.38), were more
      likely to receive a timely CT request in hospital. CONCLUSIONS: This study
      highlights the importance of hospital prealerting, accurate stroke recognition,
      and recording of onset time. Those not recognised with stroke in a prehospital
      setting appear to be excluded from the possibility of rapid treatment in
      hospital, even before they have been seen by a specialist.

PMID- 24099830
TI  - Epidemiology, management and outcome of paracetamol poisoning in an inner city
      emergency department.
AB  - BACKGROUND: Paracetamol poisoning accounts for just under half of all self
      poisoning cases that present to hospitals in England. Treatment with
      acetylcysteine is routine, yet recommendations regarding its use vary
      internationally and have recently been revised in England and Wales. METHODS:
      Data on all cases of paracetamol poisoning presenting to an adult inner city
      emergency department between May 2011 and April 2012 were prospectively collected
      using the Bristol Self-harm Surveillance Register. RESULTS: Paracetamol overdoses
      accounted for 44% of adult self-poisoning cases. A quarter (26.9%) of patients
      required treatment with acetylcysteine and it was estimated that recent changes
      in treatment guidelines would increase that proportion to 32.6%. Paracetamol
      concentration was positively associated with the risk of any adverse reaction to
      acetylcysteine. 22.5% of patients experienced anaphylactoid reactions to
      acetylcysteine. There was no clear evidence of an association between risk of
      anaphylactoid reaction and blood paracetamol levels. Patients presenting with
      blood paracetamol levels greater than 200 mg/L at 4 h post-ingestion were at
      greater risk of repeat self-harm (HR 2.17, 95% CI 1.11 to 4.21, p=0.033).
      DISCUSSION: The recent changes in UK treatment guidelines are expected to
      increase the proportion of our population requiring acetylcysteine by 5.7%. We
      found no clear evidence that risk of anaphylactoid or more general adverse
      reaction to acetylcysteine was increased in patients presenting with lower blood
      paracetamol concentrations. Blood paracetamol level was highlighted as a
      potentially useful clinical indicator for risk of repeat self-harm.

PMID- 24099831
TI  - Clinical navigation for beginners: the clinical utility and safety of the
      Paramedic Pathfinder.
AB  - BACKGROUND: English Ambulance Services are faced with annual increases in
      emergency demand. Addressing the demand for low acuity emergency calls relies
      upon the ability of ambulance clinicians to accurately identify the most
      appropriate destination or referral pathway. Given the risk of undertriage, the
      challenge is to develop processes that can safely determine patient dispositions,
      thereby increasing the number of patients receiving care closer to home. AIMS:
      The aim of the study was to evaluate the clinical utility and safety of triage
      support tools (Paramedic Pathfinders). METHODS: Two triage filters (Pathfinders)
      were developed (one medical, one trauma). These were applied by ambulance
      clinicians to 481 patients who had been transported to emergency departments
      (EDs). Preferred (gold standard) patient dispositions were established by senior
      medical practitioners using both ambulance and ED clinical records. The clinical
      utility of ambulance clinicians using Pathfinders was evaluated against this gold
      standard. RESULTS: The Medical Pathfinder was applied to 367 patients (76.3%) and
      the Trauma Pathfinder to 114 (23.7%). Agreement between ambulance clinician and
      gold standard was achieved in 387 cases (80.5%) giving the tools a combined
      sensitivity of 94.83% and specificity of 57.9%. 20.9% of medical patients and
      30.7% of trauma patients who had been transported to hospital could have been
      safely cared for elsewhere. CONCLUSIONS: Ambulance clinicians using Pathfinders
      have demonstrated acceptable levels of sensitivity in identifying patients who
      require ED care. The actual impact of the tools in clinical practice will be
      dependent on the provision of suitable alternatives to ED.

PMID- 24099832
TI  - The impact of thunderstorm asthma on emergency department attendances across
      London during July 2013.
AB  - BACKGROUND: This study illustrates the potential of using emergency department
      attendance data, routinely accessed as part of a national syndromic surveillance
      system, to monitor the impact of thunderstorm asthma. METHODS: The Emergency
      Department Syndromic Surveillance System (EDSSS) routinely monitors anonymised
      attendance data on a daily basis across a sentinel network of 35 emergency
      departments. Attendance data for asthma, wheeze and difficulty breathing are
      analysed on a daily basis. RESULTS: A statistically significant spike in asthma
      attendances in two EDSSS emergency departments in London was detected on 23 July
      2013, coinciding with a series of large violent thunderstorms across southern
      England. There was also an increase in the reported severity of these
      attendances. CONCLUSIONS: This preliminary report illustrates the potential of
      the EDSSS to monitor the impact of thunderstorms on emergency department asthma
      attendances. Further work will focus on how this system can be used to quantify
      the impact on emergency departments, thus potentially improving resource planning
      and also adding to the thunderstorm asthma evidence-base.

PMID- 24099833
TI  - Near-patient testing for RSV in the emergency department.

PMID- 24099834
TI  - Treatable Leigh-like encephalopathy presenting in adolescence.
AB  - Wernicke's encephalopathy is a triad of ophthalmoplegia, ataxia and confusion
      seen in alcoholics with dietary vitamin B1 (thiamine) deficiency. A rare genetic
      defect of thiamine transporter-2 may lead to similar clinical features, biotin
      thiamine responsive basal ganglia disease (BTBGD). A 15-year-old girl developed
      rapid onset ptosis and ophthalmoplegia evolving into a subacute encephalopathy.
      Neuroimaging demonstrated symmetrical basal ganglia and mid-brain lesions
      reminiscent of Leigh's subacute necrotising encephalomyelopathy. Oral biotin and
      thiamine were started, and symptoms improved dramatically the next day. The
      therapeutic response suggested SLC19A3, encoding thiamine transporter-2, as a
      strong candidate gene and Sanger sequencing revealed a novel homozygous
      c.517A>G;p.Asn173Asp mutation, which segregated with disease within the family.
      BTBGD is a potentially treatable neurological disorder and should be considered
      in the differential diagnosis of Leigh syndrome and Wernicke's encephalopathy.
      Since delayed treatment results in permanent neurological dysfunction or death,
      prompt diagnosis and early initiation of biotin and thiamine therapy are
      essential. 

PMID- 24099836
TI  - Prevalence of epilepsy in a cohort of patients with multiple sclerosis.
AB  - INTRODUCTION: Epilepsy prevalence is 0.27-1.7% in general population. However,
      higher figures have been reported in Multiple Sclerosis (MS) patients, suggesting
      this association is not coincidental. METHODS: We retrospectively reviewed the
      records of MS patients seen between 2009 and 2012 at Pontificia Universidad
      Catolica of Chile's Multiple Sclerosis Center. RESULTS: Of 310 MS patients, ten
      had the diagnosis of epilepsy (3.2%). These patients were younger, and had an
      earlier onset of symptoms of MS compared to the group without epilepsy (32 vs. 40
      years, p=0.04 and 25 vs. 32 years, p=0.02, respectively). In 4 patients, seizures
      were the first MS symptom and the most frequent seizure type was partial
      secondary generalized (6 patients). MRI showed cortical lesions in all patients.
      Patients with poor epilepsy control (frequent seizures or development of status
      epilepticus) had lower brain volumes and worse cognitive performance. All
      patients received antiepileptic drugs as well as immunomodulatory therapy.
      CONCLUSION: Patients with epilepsy and MS are younger and have an earlier onset
      of symptoms. Since most seizures were partial, the presence of cortical lesions
      and progressive brain atrophy could probably be the pathophysiological mechanism
      underlying this association.

PMID- 24099835
TI  - Connectivity between right inferior frontal gyrus and supplementary motor area
      predicts after-effects of right frontal cathodal tDCS on picture naming speed.
AB  - BACKGROUND: Cathodal transcranial direct current stimulation (tDCS) of the right
      frontal cortex improves language abilities in post-stroke aphasic patients. Yet
      little is known about the effects of right frontal cathodal tDCS on normal
      language function. OBJECTIVE/HYPOTHESIS: To explore the cathodal tDCS effects of
      the right-hemispheric homologue of Broca's area on picture naming in healthy
      individuals. We hypothesized that cathodal tDCS improves picture naming and that
      this effect is determined by the anatomical and functional connectivity of the
      targeted region. METHODS: Cathodal and sham tDCS were applied to the right
      inferior frontal gyrus in 24 healthy subjects before a picture-naming task. All
      participants were studied with magnetic resonance imaging at pre-interventional
      baseline. Probabilistic tractography and dynamic causal modeling of functional
      brain activity during a word repetition task were applied to characterize
      anatomical and functional connectivity. RESULTS: Subjects named pictures faster
      after cathodal relative to sham tDCS. The accelerating effect of tDCS was
      explained by a reduced frequency of very slow responses. tDCS-induced
      acceleration of picture naming correlated with larger volumes of the tract
      connecting the right Broca's area and the supplementary motor area (SMA) and
      greater functional coupling from the right SMA to the right Broca's area.
      CONCLUSIONS: The results support the notion that the after-effects of tDCS on
      brain function are at least in part determined by the anatomical and functional
      connectivity of the targeted region.

PMID- 24099837
TI  - Differential expression of adipokines in infrapatellar fat pad (IPFP) and
      synovium of osteoarthritis patients and healthy individuals.

PMID- 24099838
TI  - Sentinel lymph node mapping with pathologic ultrastaging: a valuable tool for
      assessing nodal metastasis in low-grade endometrial cancer with superficial
      myoinvasion.
AB  - OBJECTIVE: To report the incidence of nodal metastases in patients presenting
      with presumed low-grade endometrioid adenocarcinomas using a sentinel lymph node
      (SLN) mapping protocol including pathologic ultrastaging. METHODS: All patients
      from 9/2005 to 12/2011 who underwent endometrial cancer staging surgery with
      attempted SLN mapping for preoperative grade 1 (G1) or grade 2 (G2) tumors with
      <50% invasion on final pathology, were included. All lymph nodes were examined
      with hematoxylin and eosin (H&E). Negative SLNs were further examined using an
      ultrastaging protocol to detect micrometastases and isolated tumor cells.
      RESULTS: Of 425 patients, lymph node metastasis was found in 25 patients (5.9%)
      on final pathology-13 cases on routine H&E, 12 cases after ultrastaging. Patients
      whose tumors had a DMI <50% were more likely to have positive SLNs on routine H&E
      (p<0.005) or after ultrastaging (p=0.01) compared to those without myoinvasion.
      CONCLUSIONS: Applying a standardized SLN mapping algorithm with ultrastaging
      allows for the detection of nodal disease in a presumably low-risk group of
      patients who in some practices may not undergo any nodal evaluation. Ultrastaging
      of SLNs can likely be eliminated in endometrioid adenocarcinoma with no
      myoinvasion. The long-term clinical significance of ultrastage-detected nodal
      disease requires further investigation as recurrences were noted in some of these
      cases.

PMID- 24099839
TI  - Prevention of blood transfusion with intravenous iron in gynecologic cancer
      patients receiving platinum-based chemotherapy.
AB  - OBJECTIVES: To compare the efficacy of intravenous iron and oral iron for
      prevention of blood transfusions in gynecologic cancer patients receiving
      platinum-based chemotherapy. MATERIALS AND METHODS: Sixty-four non anemic
      gynecologic cancer patients receiving adjuvant platinum-based chemotherapy were
      stratified and randomized according to baseline hemoglobin levels and
      chemotherapy regimen. The study group received 200mg of intravenous iron sucrose
      immediately after each chemotherapy infusion. The control group received oral
      ferrous fumarate at a dose of 200mg three times a day. Complete blood count was
      monitored before each chemotherapy infusion. Blood transfusions were given if
      hemoglobin level was below 10mg/dl. RESULTS: There were 32 patients in each
      group. No significant differences in baseline hemoglobin levels and baseline
      characteristics were demonstrated between both groups. Nine patients (28.1%) in
      the study group and 18 patients (56.3%) in the control group required blood
      transfusion through 6 cycles of chemotherapy (p=0.02). Fewer median number of
      total packed red cell units were required in the study group compared to the
      control group (0 and 0.5 unit, respectively, p=0.04). Serious adverse events and
      hypersensitivity reactions were not reported. However, constipation was
      significantly higher in the control group (3.1% and 40.6%, p=<0.001).
      CONCLUSIONS: Intravenous iron is an effective, well-tolerated treatment for
      primary prevention of blood transfusions in gynecologic cancer patients receiving
      platinum-based chemotherapy, associated with less constipation than the oral
      formulation.

PMID- 24099840
TI  - How are the motor system activity and functional connectivity between the
      cognitive and sensorimotor systems modulated by athletic expertise?
AB  - Expertise offers a unique insight into how our brain functions. The purpose of
      this experiment was to determine if motor system activity and functional
      connectivity between the cognitive system and sensorimotor system is
      differentially modulated by an individual's level of expertise. This goal was
      achieved through the acquisition of functional neuroimaging data in 10 expert
      volleyball players and 10 novice individuals who were presented with a series of
      sentences describing possible technical volleyball-specific motor acts and acts
      that cannot be performed as positive ("Do ...!") or negative ("Don't ...")
      commands, while they were silently reading them and deciding whether the actions
      were technically feasible or not. Compared with novices, experts' activity in the
      left primary motor cortex hand area (M1) and in the left premotor cortex (Pm) was
      decreased by impossible actions presented as positive commands. Sensorimotor
      activation in response to action-related stimuli is not that automatic as held
      since we found that these areas were deactivated during the task, and their
      functional connectivity to the primary visual cortex was strengthened for
      possible actions presented as positive commands, reflecting the neural processes
      underlying the interaction between motor and visual imagery. These results
      suggest that the neural activity within the key areas implicitly triggered by
      motor simulation is a function of the expertise, action feasibility, and context.

PMID- 24099841
TI  - Corrosion behavior of tantalum-coated cobalt-chromium modular necks compared to
      titanium modular necks in a simulator test.
AB  - This study compared the corrosion behavior of tantalum-coated cobalt-chromium
      modular necks with that of titanium alloy modular necks at their junction to
      titanium-alloy femoral stem. Tests were performed in a dry assembly and two wet
      assemblies, one contaminated with calf serum and the other contaminated with calf
      serum and bone particles. Whereas the titanium modular neck tested in the dry
      assembly showed no signs of corrosion, the titanium modular necks tested in both
      wet assemblies showed marked depositions and corrosive attacks. By contrast, the
      tantalum-coated cobalt-chromium modular necks showed no traces of corrosion or
      chemical attack in any of the three assemblies. This study confirms the
      protective effect of tantalum coating the taper region of cobalt-chromium modular
      neck components, suggesting that the use of tantalum may reduce the risk of
      implant failure due to corrosion. 

PMID- 24099842
TI  - Dynamic and static contributions of the cerebrovasculature to the resting-state
      BOLD signal.
AB  - Functional magnetic resonance imaging (fMRI) in the resting state, particularly
      fMRI based on the blood-oxygenation level-dependent (BOLD) signal, has been
      extensively used to measure functional connectivity in the brain. However, the
      mechanisms of vascular regulation that underlie the BOLD fluctuations during rest
      are still poorly understood. In this work, using dual-echo pseudo-continuous
      arterial spin labeling and MR angiography (MRA), we assess the spatio-temporal
      contribution of cerebral blood flow (CBF) to the resting-state BOLD signals and
      explore how the coupling of these signals is associated with regional
      vasculature. Using a general linear model analysis, we found that statistically
      significant coupling between resting-state BOLD and CBF fluctuations is highly
      variable across the brain, but the coupling is strongest within the major nodes
      of established resting-state networks, including the default-mode, visual, and
      task-positive networks. Moreover, by exploiting MRA-derived large vessel
      (macrovascular) volume fraction, we found that the degree of BOLD-CBF coupling
      significantly decreased as the ratio of large vessels to tissue volume increased.
      These findings suggest that the portion of resting-state BOLD fluctuations at the
      sites of medium-to-small vessels (more proximal to local neuronal activity) is
      more closely regulated by dynamic regulations in CBF, and that this CBF
      regulation decreases closer to large veins, which are more distal to neuronal
      activity. 

PMID- 24099843
TI  - Serial optical coherence scanner for large-scale brain imaging at microscopic
      resolution.
AB  - We describe a serial optical coherence scanner (SOCS) for high resolution imaging
      of ex-vivo brain. SOCS integrates a multi-contrast optical coherence tomography
      and a vibratome slicer to establish comprehensive brain anatomy and fiber
      pathways in three-dimensional space. Rat brain images are demonstrated by
      utilizing intrinsic optical contrasts including back-scattering, birefringence
      and optic axis orientation, which are simultaneously generated from the same
      dataset. Volumetric images from serial scans are combined to realize large scale
      brain maps. Nerve fiber tracts are globally described in 3D by retardance, and
      delicately delineated by cross-polarization at the resolution of 15*15*5.5MUm(3).
      In-plane orientations of the tracts are quantified by optic axis orientation.
      SOCS offers a new solution for complete reconstructions of macroscopic tissues
      such as primate and human brains at microscopic resolution. The technique also
      opens up varieties of opportunities for connectome studies and systematic
      investigations on neurological diseases and brain disorders. 

PMID- 24099845
TI  - Non-Gaussian methods and high-pass filters in the estimation of effective
      connections.
AB  - We consider several alternative ways of exploiting non-Gaussian distributional
      features, including some that can in principle identify direct, positive feedback
      relations (graphically, 2-cycles) and combinations of methods that can identify
      high dimensional graphs. All of the procedures are implemented in the TETRAD
      freeware (Ramsey et al., 2013). We show that in most cases the limited accuracy
      of the several non-Gaussian methods in the Smith et al. (2011) simulations can be
      attributed to the high-pass Butterworth filter used in that study. Without that
      filter, or with the filter in the widely used FSL program (Jenkinson et al.,
      2012), the directional accuracies of several of the non-Gaussian methods are at
      or near ceiling in many conditions of the Smith et al. simulation. We show that
      the improvement of an apparently Gaussian method (Patel et al., 2006) when
      filtering is removed is due to non-Gaussian features of that method introduced by
      the Smith et al. implementation. We also investigate some conditions in which
      multi-subject data help with causal structure identification using higher
      moments, notably with non-stationary time series or with 2-cycles. We illustrate
      the accuracy of the methods with more complex graphs with and without 2-cycles,
      and with a 500 node graph; to illustrate applicability and provide a further test
      we apply the methods to an empirical case for which aspects of the causal
      structure are known. Finally, we note a number of cautions and issues that remain
      to be investigated, and some outstanding problems for determining the structure
      of effective connections from fMRI data. 

PMID- 24099844
TI  - Temporal and spatial evolution of grey matter atrophy in primary progressive
      multiple sclerosis.
AB  - Grey matter (GM) atrophy occurs early in primary progressive MS (PPMS), but it is
      unknown whether its progression involves different brain regions at different
      rates, as is seen in other neurodegenerative diseases. We aimed to investigate
      the temporal and regional evolution of GM volume loss over 5years and its
      relationship with disability progression in early PPMS. We studied 36 patients
      with PPMS within five years from onset and 19 age and gender-matched healthy
      controls with clinical and imaging assessments at study entry and yearly for
      3years and then at 5years. Patients were scored on the expanded disability status
      scale (EDSS) and MS Functional Composite (MSFC) at each time-point. An unbiased
      longitudinal voxel-based morphometry approach, based on high-dimensional spatial
      alignment within-subject, was applied to the serial imaging data. The rate of
      local (voxel-wise) volume change per year was compared between groups and its
      relationship with clinical outcomes was assessed. Patients deteriorated
      significantly during the five years follow-up. Patients showed a greater decline
      of GM volume (p<0.05, FWE-corrected) bilaterally in the cingulate cortex,
      thalamus, putamen, precentral gyrus, insula and cerebellum when compared to
      healthy controls over five years, although the rate of volume loss varied across
      the brain, and was the fastest in the cingulate cortex. Significant (p<0.05, FWE
      corrected) volume loss was detected in the left insula, left precuneus, and right
      cingulate cortex in patients at three years, as compared to baseline, whilst the
      bilateral putamen and the left superior temporal gyrus showed volume loss at five
      years. In patients, there was a relationship between a higher rate of volume loss
      in the bilateral cingulate cortex and greater clinical disability, as measured by
      the MSFC, at five years (Pearson's r=0.49, p=0.003). Longitudinal VBM
      demonstrated that the progression of GM atrophy in PPMS occurs at different rates
      in different regions across the brain. The involvement of the cingulate cortex
      occurs early in the disease course, continues at a steady rate throughout the
      follow-up period and is associated with patient outcome. These findings provide
      new insights into the characteristics of GM atrophy across the brain in MS, and
      have potential consequences for the selection of brain atrophy as an outcome
      measure in neuroprotective clinical trials. 

PMID- 24099846
TI  - Two-dimensional spatial tuning for saccades in human parieto-frontal cortex.
AB  - Saccades in the frontoparallel plane are targeted at two-dimensional (2D)
      locations, defined by direction and amplitude. Macaque neurophysiology has shown
      that these dimensions are jointly represented in single intraparietal sulcus
      (IPS) and frontal eye fields (FEF) neurons, constituting multiple maps of 2D
      saccade space. Human fMRI has shown that the direction of the saccade is
      topographically represented across large neuronal groups. However, it is unknown
      whether both direction and amplitude are separable dimensions at the voxel level
      and whether these tuning variables are organized in large-scale topographic maps.
      We used fMRI to address these issues in subjects performing an instructed-delay
      saccade task to 18 locations (6 directions, 3 amplitudes). Singular value
      decomposition was applied to the corresponding response field of each voxel,
      providing an index of the separability into direction and amplitude tuning. Our
      findings show that saccade location tuning is composed of separable direction and
      amplitude components within voxels across the parieto-frontal network. In both
      IPS and FEF there were amplitude gradients and reversals of direction tuning
      across voxels, with a medio-lateral gradient of decreasing saccade amplitude
      along the IPS. These findings reveal the 2D cortical organization of saccade
      space within and across voxels and hold great potential for the study of other
      sensorimotor systems.

PMID- 24099848
TI  - Dopamine receptor 4 promoter polymorphism modulates memory and neuronal responses
      to salience.
AB  - Animal models and human functional imaging data implicate the dopamine system in
      mediating enhanced encoding of novel stimuli into human memory. A separate line
      of investigation suggests an association between a functional polymorphism in the
      promoter region for the human dopamine 4 receptor gene (DRD4) and sensitivity to
      novelty. We demonstrate, in two independent samples, that the -521C>T DRD4
      promoter polymorphism determines the magnitude of human memory enhancement for
      contextually novel, perceptual oddball stimuli in an allele dose-dependent
      manner. The genotype-dependent memory enhancement conferred by the C allele is
      associated with increased neuronal responses during successful encoding of
      perceptual oddballs in the ventral striatum, an effect which is again allele dose
      dependent. Furthermore, with repeated presentations of oddball stimuli, this
      memory advantage decreases, an effect mirrored by adaptation of activation in the
      hippocampus and substantia nigra/ventral tegmental area in C carriers only. Thus,
      a dynamic modulation of human memory enhancement for perceptually salient stimuli
      is associated with activation of a dopaminergic-hippocampal system, which is
      critically dependent on a functional polymorphism in the DRD4 promoter region. 

PMID- 24099849
TI  - Talking about social conflict in the MRI scanner: neural correlates of being
      empathized with.
AB  - This study investigated the emotional effects and neural correlates of being
      empathized with while speaking about a currently experienced real-life social
      conflict during fMRI. Specifically, we focused on the effects of cognitive
      empathy in the form of paraphrasing, a technique regularly used in conflict
      resolution. 22 participants underwent fMRI while being interviewed on their
      social conflict and receiving empathic or unempathic responses from the
      interviewer. Skin conductance response (SCR) and self-report ratings of feeling
      understood and emotional valence were used to assess emotional responses. Results
      confirm previous findings indicating that cognitive empathy exerts a positive
      short-term effect on emotions in social conflict, while at the same time
      increasing autonomic arousal reflected by SCR. Effects of paraphrasing and
      unempathic interventions as indicated by self-report ratings varied depending on
      self-esteem, pre-interview negative affect, and participants' empathy quotient.
      Empathic responses engaged a fronto-parietal network with activity in the right
      precentral gyrus (PrG), left middle frontal gyrus (MFG), left inferior parietal
      gyrus (IPG), and right postcentral gyrus (PoG). Processing unempathic responses
      involved a fronto-temporal network with clusters peaking in the left inferior
      frontal gyrus, pars triangularis (IFGTr), and right temporal pole (TP). A
      specific modeling of feeling misunderstood activated a network consisting of the
      IFG, left TP, left Heschl gyrus, IFGTr, and right precuneus, extending to several
      limbic regions, such as the insula, amygdala, putamen, and anterior cingulate
      cortex/right middle cingulum (ACC/MCC). The results support the effectiveness of
      a widely used conflict resolution technique, which may also be useful for
      professionals who regularly deal with and have to de-escalate situations highly
      charged with negative emotion, e.g. physicians or judges. 

PMID- 24099847
TI  - Distinct brain activity in processing negative pictures of animals and objects -
      the role of human contexts.
AB  - Previous studies have shown that the amygdala is important in processing not only
      animate entities but also social information. It remains to be determined to what
      extent the factors of category and social context interact to modulate the
      activities of the amygdala and cortical regions. In this study, pictures
      depicting animals and inanimate objects in negative and neutral levels were
      presented. The contexts of the pictures differed in whether they included
      human/human parts. The factors of valence, arousal, familiarity and complexity of
      pictures were controlled across categories. The results showed that the amygdala
      activity was modulated by category and contextual information. Under the nonhuman
      context condition, the amygdala responded more to animals than objects for both
      negative and neutral pictures. In contrast, under the human context condition,
      the amygdala showed stronger activity for negative objects than animals. In
      addition to cortical regions related to object action, functional and effective
      connectivity analyses showed that the anterior prefrontal cortex interacted more
      with the amygdala for negative objects (vs. animals) in the human context
      condition, by a top-down modulation of the anterior prefrontal cortex to the
      amygdala. These results highlighted the effects of category and human contexts on
      modulating brain activity in emotional processing. 

PMID- 24099850
TI  - Patterns of resting state connectivity in human primary visual cortical areas: a
      7T fMRI study.
AB  - The nature and origin of fMRI resting state fluctuations and connectivity are
      still not fully known. More detailed knowledge on the relationship between
      resting state patterns and brain function may help to elucidate this matter. We
      therefore performed an in depth study of how resting state fluctuations map to
      the well known architecture of the visual system. We investigated resting state
      connectivity at both a fine and large scale within and across visual areas V1, V2
      and V3 in ten human subjects using a 7Tesla scanner. We found evidence for
      several coexisting and overlapping connectivity structures at different spatial
      scales. At the fine-scale level we found enhanced connectivity between the same
      topographic locations in the fieldmaps of V1, V2 and V3, enhanced connectivity to
      the contralateral functional homologue, and to a lesser extent enhanced
      connectivity between iso-eccentric locations within the same visual area.
      However, by far the largest proportion of the resting state fluctuations occurred
      within large-scale bilateral networks. These large-scale networks mapped to some
      extent onto the architecture of the visual system and could thereby obscure fine
      scale connectivity. In fact, most of the fine-scale connectivity only became
      apparent after the large-scale network fluctuations were filtered from the
      timeseries. We conclude that fMRI resting state fluctuations in the visual cortex
      may in fact be a composite signal of different overlapping sources. Isolating the
      different sources could enhance correlations between BOLD and
      electrophysiological correlates of resting state activity. 

PMID- 24099851
TI  - The structural-functional connectome and the default mode network of the human
      brain.
AB  - An emerging field of human brain imaging deals with the characterization of the
      connectome, a comprehensive global description of structural and functional
      connectivity within the human brain. However, the question of how functional and
      structural connectivity are related has not been fully answered yet. Here, we
      used different methods to estimate the connectivity between each voxel of the
      cerebral cortex based on functional magnetic resonance imaging (fMRI) and
      diffusion tensor imaging (DTI) data in order to obtain observer-independent
      functional-structural connectomes of the human brain. Probabilistic fiber
      tracking and a novel global fiber-tracking technique were used to measure
      structural connectivity whereas for functional connectivity, full and partial
      correlations between each voxel pair's fMRI-timecourses were calculated. For
      every voxel, two vectors consisting of functional and structural connectivity
      estimates to all other voxels in the cortex were correlated with each other. In
      this way, voxels structurally and functionally connected to similar regions
      within the rest of the brain could be identified. Areas forming parts of the
      'default mode network' (DMN) showed the highest agreement of structure-function
      connectivity. Bilateral precuneal and inferior parietal regions were found using
      all applied techniques, whereas the global tracking algorithm additionally
      revealed bilateral medial prefrontal cortices and early visual areas. There were
      no significant differences between the results obtained from full and partial
      correlations. Our data suggests that the DMN is the functional brain network,
      which uses the most direct structural connections. Thus, the anatomical profile
      of the brain seems to shape its functional repertoire and the computation of the
      whole-brain functional-structural connectome appears to be a valuable method to
      characterize global brain connectivity within and between populations. 

PMID- 24099852
TI  - Osmotically driven membrane process for the management of urban runoff in coastal
      regions.
AB  - An osmotic detention pond was proposed for the management of urban runoff in
      coastal regions. Forward osmosis was employed as a bridge to utilize natural
      osmotic energy from seawater for concentrating and reusing urban runoff water,
      and as a barrier to reject runoff-derived contaminants. The process was
      demonstrated by a lab scale testing using synthetic urban runoff (as the feed
      solution) and synthetic seawater (as the draw solution). The submerged forward
      osmosis process was conducted under neutral, acidic and natural organic matter
      fouling condition, respectively. Forward osmosis flux decline was mainly
      attributed to the dilution of seawater during a semi-batch process in lab scale
      testing. However, it is possible to minimize flux decrease by maintaining a
      constant salinity at the draw solution side. Various changes in urban runoff
      water quality, including acidic conditions (acid rain) and natural organic matter
      presence, did not show significant effects on the rejection of trace metals and
      phosphorus, but influenced salt leakage and the rejection of nitrate and total
      nitrogen. Rejection of trace metals varied from 98% to 100%, phosphorus varied
      from 97% to 100, nitrate varied from 52% to 94% and total nitrogen varied from
      65% to 85% under different feed water conditions. The work described in this
      study contributes to an integrated system of urban runoff management, seawater
      desalination and possible power generation in coastal regions to achieve a
      sustainable solution to the water-energy nexus. 

PMID- 24099853
TI  - Feasibility of proton-activated implantable markers for proton range verification
      using PET.
AB  - Proton beam range verification using positron emission tomography (PET) currently
      relies on proton activation of tissue, the products of which decay with a short
      half-life and necessitate an on-site PET scanner. Tissue activation is, however,
      negligible near the distal dose fall-off region of the proton beam range due to
      their high interaction energy thresholds. Therefore Monte Carlo simulation is
      often supplemented for comparison with measurement; however, this also may be
      associated with systematic and statistical uncertainties. Therefore, we sought to
      test the feasibility of using long-lived proton-activated external materials that
      are inserted or infused into the target volume for more accurate proton beam
      range verification that could be performed at an off-site PET scanner. We
      irradiated samples of >=98% (18)O-enriched water, natural Cu foils, and >97%
      (68)Zn-enriched foils as candidate materials, along with samples of tissue
      equivalent materials including (16)O water, heptane (C7H16), and polycarbonate
      (C16H14O3)n, at four depths (ranging from 100% to 3% of center of modulation
      (COM) dose) along the distal fall-off of a modulated 160 MeV proton beam. Samples
      were irradiated either directly or after being embedded in Plastic Water(r) or
      balsa wood. We then measured the activity of the samples using PET imaging for 20
      or 30 min after various delay times. Measured activities of candidate materials
      were up to 100 times greater than those of the tissue-equivalent materials at the
      four distal dose fall-off depths. The differences between candidate materials and
      tissue-equivalent materials became more apparent after longer delays between
      irradiation and PET imaging, due to the longer half-lives of the candidate
      materials. Furthermore, the activation of the candidate materials closely
      mimicked the distal dose fall-off with offsets of 1 to 2 mm. Also, signals from
      the foils were clearly visible compared to the background from the activated
      Plastic Water(r) and balsa wood phantoms. These results indicate that markers
      made from these candidate materials could be used for in vivo proton range
      verification using an off-site PET scanner. 

PMID- 24099854
TI  - Long-term changes in the material properties of brain tissue at the implant
      tissue interface.
AB  - OBJECTIVE: Brain tissue undergoes dramatic molecular and cellular remodeling at
      the implant-tissue interface that evolves over a period of weeks after
      implantation. The biomechanical impact of such remodeling on the interface
      remains unknown. In this study, we aim to assess the changes in the mechanical
      properties of the brain-electrode interface after chronic implantation of a
      microelectrode. APPROACH: Microelectrodes were implanted in the rodent cortex at
      a depth of 1 mm for different durations-1 day (n = 4), 10-14 days (n = 4), 4
      weeks (n = 4) and 6-8 weeks (n = 7). After the initial duration of implantation,
      the microelectrodes were moved an additional 1 mm downward at a constant speed of
      10 um s(-1). Forces experienced by the microelectrode were measured during
      movement and after termination of movement. The biomechanical properties of the
      interfacial brain tissue were assessed from measured force-displacement curves
      using two separate models-a two-parameter Mooney-Rivlin hyperelastic model and a
      viscoelastic model with a second-order Prony series. MAIN RESULTS: Estimated
      shear moduli using a second-order viscoelastic model increased from 0.5-2.6 kPa
      (day 1 of implantation) to 25.7-59.3 kPa (after 4 weeks of implantation) and
      subsequently decreased to 0.8-7.9 kPa after 6-8 weeks of implantation in 6 of the
      7 animals. The estimated elastic modulus increased from 4.1-7.8 kPa on the day of
      implantation to 24-44.9 kPa after 4 weeks. The elastic modulus was estimated to
      be 6.8-33.3 kPa in 6 of the 7 animals after 6-8 weeks of implantation. The above
      estimates suggest that the brain tissue surrounding the microelectrode evolves
      from a stiff matrix with maximal shear and elastic modulus after 4 weeks of
      implantation into a composite of two different layers with different mechanical
      properties-a stiff compact inner layer surrounded by softer brain tissue that is
      biomechanically similar to brain tissue-during the first week of implantation.
      Tissue micromotion-induced stresses on the microelectrode constituted 12-55% of
      the steady-state stresses on the microelectrode on the day of implantation (n =
      4), 2-21% of the steady-state stresses after 4 weeks of implantation (n = 4), and
      4-10% of the steady-state stresses after 6-8 weeks of implantation (n = 7).
      SIGNIFICANCE: Understanding biomechanical behavior at the brain-microelectrode
      interface is necessary for the long-term success of implantable neuroprosthetics
      and microelectrode arrays. Such quantitative physical characterization of the
      dynamic changes in the electrode-tissue interface will (a) drive the design and
      development of more mechanically optimal, chronic brain implants, and (b) lead to
      new insights into key cellular and molecular events such as neuronal adhesion,
      migration and function in the immediate vicinity of the brain implant.

PMID- 24099855
TI  - Acute kidney injury in an internal medicine ward in a Portuguese quaternary
      hospital.
AB  - BACKGROUND: The term acute kidney injury (AKI) was proposed to reflect the wide
      spectrum of traditional acute renal failure. RIFLE classification stratifies AKI
      into three classes of severity and two classes of outcome. AKIN classification
      proposes an improvement regarding RIFLE in the stratification of AKI, while
      recently published KDIGO guidelines comprise characteristics of both RIFLE and
      AKIN. There are no published studies on the utility and measure of agreement
      between classifications in patients admitted to internal medicine wards. METHODS:
      Prospective study undertaken in two internal medicine wards in a Portuguese
      hospital. Patients admitted for a minimum of 72 h, with a diagnosis of AKI or
      acute-on-chronic kidney disease at admission or during hospitalisation, were
      included. RIFLE, AKIN and KDIGO criteria were applied for identification of AKI
      and stratification into risk groups. RESULTS: Sixty-nine patients were included,
      with a mean age of 79.7+/-10.0 years and mean GFR of 21.7+/-8.8 mL/min/1.73 m2.
      Hypovolaemia due to dehydration was the main cause of AKI (53.6%) and, thereby,
      RIFLE classification identified a higher number of patients as having AKI,
      compared to AKIN (94.2% vs. 84.1%). Most patients (69.6%) recovered to their
      baseline renal function, however fifteen patients (21.7%) died, 53.3% presenting
      more severe kidney disease. CONCLUSIONS: Our results demonstrate good concordance
      and correlation between RIFLE, AKIN and KDIGO criteria for the diagnosis of AKI
      (p<0.001 at initial and final assessment). The authors support the need for
      further improvement of the classification, ultimately through the use of new
      biomarkers capable of earlier identification of patients at risk.

PMID- 24099856
TI  - [A rapidly-growing gastric schwannoma or GIST?: a case report and literature
      review].

PMID- 24099857
TI  - [Endoscopic retrograde cholangiopancreatography in patients with anatomic
      abnormalities of the stomach due to surgery].
AB  - INTRODUCTION: In patients who have undergone partial gastric resections, the
      difficulty of performing endoscopic retrograde cholangiopancreatography (ERCP) is
      increased due to the resulting anatomic abnormality. AIM: To review our
      experience of ERCP in patients with Billroth II gastrectomy and other types of
      gastrectomy (Billroth I and indeterminate) in our center. MATERIAL AND METHODS:
      We included all patients with Billroth II gastrectomy or other types of
      gastrectomy undergoing ERCP in a 19-year period. RESULTS: We included 233
      patients (91% men and 9% women) from 1993 to 2012. A total of 88.4% of the
      patients had undergone Billroth II and 11.6% had undergone other types of
      gastrectomy, with an ERCP success rate of 51.9% and 55.6%, respectively. The most
      common causes of failure were inability to cannulate (44%) and failure to
      identify the papilla (39.6%). The final diagnosis was choledocholithiasis in
      31.8%. The mean number of sessions was 1.09. The complications rate was 2.6%.
      CONCLUSIONS: The success of ERCP is influenced by the technical difficulty. For
      this reason, the success rate in our center was slightly over 50%, but with few
      complications.

PMID- 24099858
TI  - Simultaneous determination of blonanserin and its four metabolites in human
      plasma using ultra-performance liquid chromatography-tandem mass spectrometry.
AB  - A sensitive and rapid method based on ultra-performance liquid chromatography
      coupled with tandem mass spectrometry (UPLC-MS/MS) was developed and validated
      for the simultaneous determination of blonanserin, its major active metabolite (N
      deethyl form) and other three metabolites (N-oxide form, Ethylenediamine form and
      Carboxylate form) in human plasma. Plasma samples were pre-purified by solid
      phase extraction (SPE) and analyzed using a gradient chromatographic separation
      over an Acquity UPLC CSH C18 column. The mobile phase consisted of acetonitrile
      water containing 5mM ammonium formate and 0.1% formic acid at a flow rate of
      0.5mL/min. Positive electrospray ionization was employed as the ionization source
      in the multiple reaction monitoring (MRM) mode. The analysis time was about
      3.5min. The method was fully validated over the concentration range of 0.01
      1ng/mL for all analytes. The lower limit of quantification (LLOQ) was 0.01ng/mL.
      Inter- and intra-batch precision was less than 15% and the accuracy was within 85
      115%. The mean extraction recoveries of all analytes at two concentration levels
      were consistent. Selectivity, matrix effect and stability were also validated.
      The method was applied to the pharmacokinetic study of blonanserin in Chinese
      healthy subjects. 

PMID- 24099859
TI  - Giving peace a chance: oxytocin increases empathy to pain in the context of the
      Israeli-Palestinian conflict.
AB  - Studies have argued that empathy to the pain of out-group members is largely
      diminished by "in-group empathy bias". Investigating the mechanism underlying the
      emotional reactions of Jewish Israeli participants toward the pain experienced by
      Palestinians in the context of the Israeli-Palestinian conflict affords a natural
      experiment that allows us to examine the role of neurohormones in emotion
      sensitivity across conflicting social groups. In a double-blind placebo
      controlled within-subject crossover design, Israeli Jewish participants were
      asked to report their empathy to the pain of in-group (Jewish), neutral out-group
      (European), and adversary out-group (Palestinian) members. Oxytocin remarkably
      increased empathy to the pain of Palestinians, attenuating the effect of in-group
      empathy bias observed under the placebo condition. This effect, we argue, is
      driven by the general role of oxytocin in increasing the salience of social
      agents which, in turn, may interfere with processes pertaining to derogation of
      out-group members during intractable conflicts. 

PMID- 24099860
TI  - Diurnal profiles of salivary cortisol and alpha-amylase change across the adult
      lifespan: evidence from repeated daily life assessments.
AB  - Salivary cortisol and alpha-amylase are known to have distinctive diurnal
      profiles. However, little is known about systematic changes in these biomarkers
      across the adult lifespan. In a study of 185 participants (aged 20-81 years),
      time-stamped salivary cortisol and alpha-amylase were collected 7 times/day over
      10 days. Samples were taken upon waking, 30 min later, and then approximately
      every 3 h until 9 pm. Multilevel models showed that older age was associated with
      increased daily cortisol secretion as indicated by greater area under the curve,
      attenuated wake-evening slopes, and more pronounced cortisol awakening responses.
      Further, older age was related to greater daily alpha-amylase output and
      attenuated wake-evening slopes. No age differences were observed regarding the
      alpha-amylase awakening response. Our findings may contribute to a better
      understanding of age-related differences in functioning of stress-related
      systems.

PMID- 24099861
TI  - Quality of maternal and paternal care predicts later stress reactivity in the
      cooperatively-breeding marmoset (Callithrix geoffroyi).
AB  - Variation in the early postnatal social environment can have lasting effects on
      hypothalamic-pituitary-adrenal (HPA) axis stress responses. Both rats and macaque
      monkeys subjected to low quality or abusive maternal care during the early
      postnatal period have more pronounced HPA responses to environmental stressors
      throughout development and into adulthood compared to animals reared in higher
      quality early maternal environments. However, little is known about the relative
      contributions to HPA stress response styles in developing offspring in species in
      which offspring care is routinely provided by group members other than the
      mother, such as in cooperatively breeding mammals. Marmoset monkeys exhibit
      cooperative offspring rearing, with fathers and older siblings providing care in
      addition to that provided by the mother. We evaluated the effects of early
      maternal, paternal, and older sibling care on HPA responses to social separation
      across development in captive white-faced marmoset offspring (Callithrix
      geoffroyi). We monitored offspring care by mothers, fathers, and older siblings
      in marmosets for the first 60 days of life. Later in development, each marmoset
      experienced three standardized social separation/novelty exposure stressors at 6,
      12, and 18 months of age. During separation, we collected urine samples and
      analyzed them via enzyme immunoassay for cortisol levels. Infants that received
      higher rates of rejections from the entire family group showed higher cortisol
      responses to social separation. This relationship was found when mothers,
      fathers, and older siblings, were analyzed separately as well. No differences in
      cortisol responses were found between offspring that received high and low rates
      of carrying or high and low rates of licking and grooming by any group member. In
      the cooperatively breeding marmoset, early social cues from multiple classes of
      caregivers may influence HPA stress responses throughout the lifespan. 

PMID- 24099862
TI  - Neutral endopeptidase (CD10) is abundantly expressed in the epididymis and
      localized to a distinct population of epithelial cells--its relevance for CNP
      degradation.
AB  - Neutral endopeptidase (NEP, metallo-endopeptidase EC 3.4.24.11; enkephalinase,
      neprilysin, CD10, CALLA) represents a major regulator of bioactivity of
      natriuretic peptides. C-type natriuretic peptide (CNP) is present in high levels
      in epididymis and seminal plasma. However, detailed expression pattern and CNP
      related function of NEP in the epididymis are unknown. Comparison of NEP protein
      levels in various organs revealed an extremely high expression in human and mouse
      epididymis. NEP was localized exclusively to apical (luminal) parts of epithelial
      cells. In man, strong NEP-immunoreactivity was associated with epithelia of
      efferent ducts and the epididymal duct including stereocilia. Segment-by-segment
      analysis in mouse revealed a distinct distribution along the epididymal duct. We
      also found the CNP receptor guanylyl cyclase B (GC-B) in epithelial cells of the
      epididymal duct. Two different NEP inhibitors decreased CNP degradation and
      increased CNP/GC-B-induced cGMP production by epididymal membranes, suggesting a
      functional involvement of NEP. Data indicate an important, previously neglected,
      role of NEP for regulation of luminal factors in the epididymis and suggest a
      novel role for CNP/GC-B in the epididymal epithelium, presumably in context of
      local water balance. 

PMID- 24099864
TI  - Battery longevity in cardiac resynchronization therapy implantable cardioverter
      defibrillators.
AB  - AIMS: Cardiac resynchronization therapy (CRT) implantable cardioverter
      defibrillators (ICDs) deliver high burden ventricular pacing to heart failure
      patients, which has a significant effect on battery longevity. The aim of this
      study was to investigate whether battery longevity is comparable for CRT-ICDs
      from different manufacturers in a contemporary cohort of patients. METHODS AND
      RESULTS: All the CRT-ICDs implanted at our institution from 1 January 2008 to 31
      December 2010 were included in this analysis. Baseline demographic and clinical
      data were collected on all patients using the electronic medical record. Detailed
      device information was collected on all patients from scanned device printouts
      obtained during routine follow-up. The primary endpoint was device replacement
      for battery reaching the elective replacement indicator (ERI). A total of 646
      patients (age 69 +/- 13 years), implanted with CRT-ICDs (Boston Scientific 173,
      Medtronic 416, and St Jude Medical 57) were included in this analysis. During 2.7
      +/- 1.5 years follow-up, 113 (17%) devices had reached ERI (Boston scientific 4%,
      Medtronic 25%, and St Jude Medical 7%, P < 0.001). The 4-year survival rate of
      device battery was significantly worse for Medtronic devices compared with
      devices from other manufacturers (94% for Boston scientific, 67% for Medtronic,
      and 92% for St Jude Medical, P < 0.001). The difference in battery longevity by
      manufacturer was independent of pacing burden, lead parameters, and burden of ICD
      therapy. CONCLUSION: There are significant discrepancies in CRT-ICD battery
      longevity by manufacturer. These data have important implications on clinical
      practice and patient outcomes.

PMID- 24099863
TI  - Fox tales: regulation of gonadotropin gene expression by forkhead transcription
      factors.
AB  - Luteinizing hormone (LH) and follicle-stimulating hormone (FSH) are produced by
      pituitary gonadotrope cells and are required for steroidogenesis, the maturation
      of ovarian follicles, ovulation, and spermatogenesis. Synthesis of LH and FSH is
      tightly regulated by a complex network of signaling pathways activated by
      hormones including gonadotropin-releasing hormone, activin and sex steroids.
      Members of the forkhead box (FOX) transcription factor family have been shown to
      act as important regulators of development, homeostasis and reproduction. In this
      review, we focus on the role of four specific FOX factors (FOXD1, FOXL2, FOXO1
      and FOXP3) in gonadotropin hormone production and discuss our current
      understanding of the molecular function of these factors derived from studies in
      mouse genetic and cell culture models. 

PMID- 24099865
TI  - Efficacy of oxaliplatin plus pemetrexed in chemotherapy pretreated metastatic
      castration-resistant prostate cancer.
AB  - BACKGROUND: Although new androgen-targeted therapies offer prolonged survival in
      metastatic castration-resistant prostate cancer (CRPC), most men still face
      progressive disease and require additional therapy. Oxaliplatin and pemetrexed
      have each shown modest activity in the treatment of CRPC. Given their favorable
      nonoverlapping toxicity profiles, we studied them in combination. PATIENTS AND
      METHODS: Men with CRPC whose disease had progressed on 1 or 2 previous
      chemotherapy regimens, including a taxane, were eligible. All participants
      received oxaliplatin 120 mg/m(2) and pemetrexed 500 mg/m(2) intravenously every
      21 days. The primary end point was response rate; objective responses were
      determined using Response Evaluation Criteria in Solid Tumors (RECIST), version
      1.0, criteria and the Prostate Cancer Working Group (1999) criteria. Secondary
      end points included progression-free survival and OS. RESULTS: Forty-seven men
      received a median of 6 cycles (range, 1-21). The overall response rate was 30%
      (95% confidence interval [CI], 18%-45%), including 10 men with RECIST responses
      of the 40 who had measurable disease (25%). Overall, 64% had a prostate-specific
      antigen (PSA) decline and 74% of men had clinical disease control (partial
      response or stable disease as their best response). Median progression-free
      survival was 5.8 months (95% CI, 3.8-7.6), with a median OS of 11.9 months. Six
      of 15 evaluable patients (40%) experienced a pain response. Nineteen patients
      (40%) experienced a grade 3 or 4 hematologic toxicity, and 16 (34%) experienced a
      grade 3 nonhematologic toxicity. One patient died while participating in the
      study. CONCLUSION: Combination oxaliplatin and pemetrexed (PemOx) is an effective
      and tolerable second- or third-line treatment for men with CRPC.

PMID- 24099866
TI  - Novel mutation identified in Cowden syndrome presenting as a gastric
      adenocarcinoma.

PMID- 24099867
TI  - Simultaneous determination of 11 preservatives in cosmetics by high-performance
      liquid chromatography.
AB  - Preservatives prevent the growth of microorganisms in foods, pharmaceuticals and
      cosmetics. There exist numerous restrictions regarding the maximum allowable
      levels of preservatives in cosmetics. We analyzed 11 regulated preservatives in
      commercial cosmetics and manufacturers need to analyze their products for quality
      control purposes. However, methods used in previous studies to date have been
      inadequate for use by public institutions and manufacturers. Therefore, an
      effective, scalable method for the analysis of preservatives in cosmetics is
      required. We developed a novel method for the simultaneous determination of 11
      regulated preservatives in cosmetics by high-performance liquid chromatography
      (HPLC). We applied the samples to a C18 column in a simple mobile phase (5 mmol/L
      ammonium formate solution and acetonitrile) with gradient elution at a flow rate
      of 1.0 mL/min at a single wavelength (230 nm). The correlation coefficients of
      the calibration curves were >0.997. The percent recoveries were 92.8-111.9% and
      the relative standard deviations were <4.3% (n = 6). The peak resolution for all
      preservatives was >1.9. Because of the simple conditions for isolation and
      complete separation, the HPLC method can be effectively applied to the analysis
      of preservatives in commercially retailed cosmetics. 

PMID- 24099868
TI  - Shingles in Alberta: before and after publicly funded varicella vaccination.
AB  - PURPOSE: A universal publicly funded chickenpox vaccination program was
      implemented in Alberta in 2002. We examine the epidemiology of medically attended
      shingles in Alberta from 1994 to 2010. METHODS: Incident shingles cases (earliest
      health service utilizations for ICD-9 053 or ICD-10-CA B02) and their co-morbid
      conditions for the 12 months prior to shingles diagnosis were identified from the
      records of Alberta's universal, publicly funded health-care insurance system for
      1994-2010. Shingles diagnostic codes at least 180 days after the first were
      classified as recurrent episodes. Denominators for rates were estimated using mid
      year population estimates from the Alberta Health Care Insurance Plan Registry.
      Annual age- and sex-specific rates were estimated. We estimated the proportion of
      all cases that were hospitalized. We explored the pattern of rates for sex, age
      group co-morbidity and year effects and their interactions. RESULTS: Crude rates
      of shingles increased over the interval 1994-2010. Most persons had only a single
      episode of shingles; 4% of cases were hospitalized. Shingles rates were higher
      among females than males. While only 2% of shingles cases had one or more co
      morbidities, this proportion was also higher for females than males. Prior to
      2002, all age groups of both sexes experienced increasing annual rates of
      shingles. However, there was a sharp decline in the rate of shingles for both
      females and males under the age of 10 years for 2002-2010, the period in which
      there was publicly funded chickenpox vaccination. CONCLUSION: The declining rates
      of shingles among persons under the age of 10 years are consistent with an impact
      of the chickenpox vaccination program. The trend of increasing rates of shingles
      among older persons began prior to implementation of vaccination.

PMID- 24099869
TI  - Well-woman visit of mothers and human papillomavirus vaccine intent and uptake
      among their 9-17 year old children.
AB  - OBJECTIVE: To examine the association between attending a well-woman clinic in
      the prior 2 years and obtaining the human papillomavirus (HPV) vaccine for their
      9-17-year-old child. METHODS: Women (n=1256) who attended reproductive health
      clinics during September 2011 to February 2013 and had >=1 children 9-17 years of
      age were asked to complete a self-administered questionnaire containing questions
      on demographic characteristics, prior well-woman visits, HPV awareness, and HPV
      vaccine intent and uptake among their adolescent children. RESULTS: Nearly 78% of
      women reported having undergone a well-woman visit during the past 2 years.
      Bivariate analysis showed that the HPV vaccine initiation (23.9% vs. 14.0%,
      P=.004) and completion (13.6% vs. 6.7%, P=.011) among 9-17 daughters differed
      between mothers who did or did not have a well-woman visit during the past 2
      years. However, intent to vaccinate them (47.2% vs. 53.3%, P=.173) did not differ
      between these two groups. With regard to 9-17 year old sons, vaccine initiation
      (10.1% vs. 9.6%, P=.871), completion (4.6% vs. 2.4%, P=.273) and intent to
      vaccinate (47.3% vs. 52.1%, P=.311) did not differ between these two groups.
      Multivariable logistic regression analyses confirmed the findings of these
      bivariate analyses after adjusting for confounder variables. CONCLUSION: The well
      woman visit may be a missed opportunity for physicians to educate their patients
      about the benefits of HPV vaccination for their adolescent children in general
      and sons in particular. Intervention studies are warranted to assess the benefits
      of using this setting to improve HPV vaccine uptake in the US.

PMID- 24099870
TI  - Assembly and immunogenicity of coronavirus-like particles carrying infectious
      bronchitis virus M and S proteins.
AB  - Infectious bronchitis virus (IBV) as an avian coronavirus is still posing a
      persistent and imminent threat to the poultry industry worldwide. Here we report
      that transfection of Sf9 cells with a single recombinant baculovirus encoding M
      and S proteins resulted in the assembly of IBV VLPs; this is the first report
      that S protein plus M protein alone were able to be assembled into VLPs for
      coronaviruses. We further showed that the generated IBV VLPs could induce humoral
      immune responses in a level comparable to that of inactivated IBV vaccine, and
      more importantly the IBV VLPs could elicit significantly higher cellular immune
      responses than the inactivated IBV vaccine. In summary, the assembly of IBV VLPs
      with M and S proteins provided a simple strategy for generating VLPs for
      coronaviruses, and the generated IBV VLPs laid a feasible foundation for the
      development of an effective vaccine against infection of IBV in the future. 

PMID- 24099871
TI  - Applicability of the Brighton Collaboration Case Definition for seizure after
      immunization in active and passive surveillance in Canada.
AB  - BACKGROUND: The Canadian Adverse Event Following Immunization Surveillance System
      (CAEFISS) receives reports via active syndromic surveillance for selected serious
      AEFI from the Canadian Immunization Monitoring Program Active (IMPACT) and via
      targeted passive surveillance from Federal/Provincial/Territorial health
      jurisdictions. Post-immunization seizure is a target of active and passive
      surveillance. Since 2009, the revised national AEFI reporting forms enable
      capture of terms specific to several Brighton Collaboration Case Definitions
      (BCCD) including generalized seizure and fever. OBJECTIVE: To evaluate
      feasibility of applying the BCCD for generalized seizure to adverse event
      following immunization (AEFI) reports collected by IMPACT and targeted passive
      surveillance (non-IMPACT). METHODS: Reports to CAEFISS coded as seizure in
      children <2 years of age (vaccination dates 1998-2011) were reviewed
      retrospectively. A BCCD level (1-5 or unclassifiable) was assigned. The effects
      of reporting source (IMPACT versus non-IMPACT), seriousness [serious (e.g.,
      hospitalized) versus non-serious], vaccination year (1998-2008 versus 2009-2011),
      and data submission method to CAEFISS (electronic versus paper) were assessed by
      stratified analysis. RESULTS: There were 459 IMPACT and 908 non-IMPACT cases
      analyzed, of which 99.6% and 27%, respectively, were serious reports. The revised
      reporting form that captured the BCCD components (2009-2011) was associated with
      increased proportions of IMPACT and non-IMPACT cases meeting the BCCD for
      generalized seizure. CONCLUSIONS: Incorporating the BCCD components (level of
      consciousness, motor manifestations and fever >=38 degrees C) into the national
      reporting form and guidelines appeared to improve the feasibility of their use in
      AEFI surveillance. This effect was more pronounced among active syndromic
      surveillance compared to targeted passive surveillance reports.

PMID- 24099872
TI  - Safety and tolerability of a live oral Salmonella typhimurium vaccine candidate
      in SIV-infected nonhuman primates.
AB  - Nontyphoidal Salmonella (NTS) serovars are a common cause of acute food-borne
      gastroenteritis worldwide and can cause invasive systemic disease in young
      infants, the elderly, and immunocompromised hosts, accompanied by high case
      fatality. Vaccination against invasive NTS disease is warranted where the disease
      incidence and mortality are high and multidrug resistance is prevalent, as in sub
      Saharan Africa. Live-attenuated vaccines that mimic natural infection constitute
      one strategy to elicit protection. However, they must particularly be shown to be
      adequately attenuated for consideration of immunocompromised subjects.
      Accordingly, we examined the safety and tolerability of an oral live attenuated
      Salmonella typhimurium vaccine candidate, CVD 1921, in an established chronic
      simian immunodeficiency virus (SIV)-infected rhesus macaque model. We evaluated
      clinical parameters, histopathology, and measured differences in mucosal
      permeability to wild-type and vaccine strains. Compared to the wild-type S.
      typhimurium strain I77 in both SIV-infected and SIV-uninfected nonhuman primate
      hosts, this live-attenuated vaccine shows reduced shedding and systemic spread,
      exhibits limited pathological disease manifestations in the digestive tract, and
      induces low levels of cellular infiltration in tissues. Furthermore, wild-type S.
      typhimurium induces increased intestinal epithelial damage and permeability, with
      infiltration of neutrophils and macrophages in both SIV-infected and SIV
      uninfected nonhuman primates compared to the vaccine strain. Based on shedding,
      systemic spread, and histopathology, the live-attenuated S. typhimurium strain
      CVD 1921 appears to be safe and well-tolerated in the nonhuman primate model,
      including chronically SIV-infected rhesus macaques.

PMID- 24099873
TI  - Pneumococcal vaccination programs and the burden of invasive pneumococcal disease
      in Ontario, Canada, 1995-2011.
AB  - BACKGROUND: In 1995, a publicly funded pneumococcal vaccination program for 23
      valent polysaccharide vaccine (PPV23) was introduced in Ontario. Conjugate
      vaccines were authorized in 2001 (PCV7), 2009 (PCV10) and 2010 (PCV13). METHODS:
      From 1995-2011, active, population-based surveillance for invasive pneumococcal
      disease (IPD) was conducted in Metropolitan Toronto and Peel Region, Canada.
      RESULTS: 6404 IPD cases were included. After PPV23 program implementation in
      1995, IPD due to PPV23 strains decreased 49% in older adults prior to PCV7
      introduction. Estimated PPV23 efficacy in vaccine eligible adults was 42.2% (95%
      CI; 28.6-53.2%). IPD incidence due to PCV7 serotypes in children <5 years
      decreased significantly after PCV7 authorization and before introduction of a
      publicly funded PCV7 program. Seven years after PCV7 program implementation, the
      incidence of IPD due to PCV7 serotypes decreased to zero in children and by 88%
      in adults, however, overall IPD incidence remained unchanged in adults. In 2011,
      the incidence of IPD was 4.5 per 100,000 in adults aged 15-64 and 19.9 per
      100,000 in adults aged over 65 years, with 45 serotypes causing disease. Between
      1995 and 2011, the case fatality rate of IPD in adults decreased 2% per year (95%
      CI, -0.9% to -3.2%). In multivariable analysis, predictors of mortality included
      older age, chronic conditions, nursing home residence, current smoking,
      bacteraemia, and illness due to serotypes 3,11A, 19A, and 19F. CONCLUSIONS: While
      vaccination programs resulted in substantial public health benefits, herd
      immunity benefits of PCV7 were seen at low pediatric vaccination rates, and the
      case fatality rate of IPD has decreased, IPD will continue to be a cause of
      considerable morbidity and mortality in adults.

PMID- 24099874
TI  - Evaluation of several approaches to immunize parents of neonates against B.
      pertussis.
AB  - BACKGROUND: Parental immunization ("cocooning") is a potentially effective
      strategy to protect neonates against Bordetella pertussis. The objective of this
      study was to evaluate three approaches to parental immunization: (1) current
      practice (single dTap dose to adolescents, one additional dose recommended in
      adults); (2) promotion of vaccination in the maternity ward, with vaccine offered
      in the community; and (3) promotion and administration of vaccine in the
      maternity ward. METHODS: We conducted a two-phase study of postpartum women in a
      tertiary care obstetric-pediatric hospital in Montreal, Canada. In Phase I,
      mothers completed a standardized questionnaire regarding pertussis knowledge,
      attitudes and immunization status. Interviews provided information on cocooning
      and pertussis vaccination, and invited parents to receive the vaccine in the
      community. In phase II, information was provided (no questionnaire) with
      vaccination offered in the maternity ward before discharge. RESULTS: Phase I
      included 101 participants; Phase II, 244. Baseline knowledge on infant disease
      severity and adult vaccine recommendations was poor. Only 6% of women were
      considered protected. In Phase I, 56.3% and 62.5% of eligible mothers and
      fathers, respectively, were willing to receive the vaccine; only 5.4% and 8.7%
      were immunized in the community. In Phase II, 53.1% and 62.6% of mothers and
      fathers, respectively, would accept vaccination; 46.9% of mothers and 60.5% of
      fathers were immunized onsite (p<0.01). CONCLUSION: Offering dTap vaccine in the
      maternity ward is an effective approach to promote cocooning and increase vaccine
      uptake. The generalizability and cost effectiveness of this strategy should be
      investigated further.

PMID- 24099875
TI  - Chikungunya virus-like particles are more immunogenic in a lethal AG129 mouse
      model compared to glycoprotein E1 or E2 subunits.
AB  - Chikungunya virus (CHIKV) causes acute illness characterized by fever and long
      lasting arthritic symptoms. The need for a safe and effective vaccine against
      CHIKV infections is on the rise due to on-going vector spread and increasing
      severity of clinical complications. Here we report the results of a comparative
      vaccination-challenge experiment in mice using three different vaccine candidates
      produced in insect cells by recombinant baculoviruses: (i) secreted (s)E1 and
      (ii) sE2 CHIKV glycoprotein subunits (2 MUg/immunization), and (iii) CHIKV virus
      like particles (VLPs) (1 MUg E2 equivalent/immunization). These experiments show
      that vaccination with two subsequent administrations of 1 MUg of Matrix M
      adjuvanted CHIKV VLPs completely protected AG129 mice from lethal CHIKV
      challenge. Vaccination with E1 and E2 subunits provided partial protection, with
      half of the mice surviving but with significantly lower neutralizing antibody
      titres as compared to the VLP vaccinated mice. This study provides evidence that
      even a modest neutralizing antibody response is sufficient to protect mice from
      CHIKV infections. Neutralization was the prominent correlate of protection. In
      addition, CHIKV VLPs provide a superior immune response and protection against
      CHIKV-induced disease in mice as compared to individual CHIKV-sE1 and -sE2
      subunits.

PMID- 24099877
TI  - Sensitive HIV-1 detection in a homogeneous solution based on an electrochemical
      molecular beacon coupled with a nafion-graphene composite film modified screen
      printed carbon electrode.
AB  - A novel electrochemical sensing assay for sensitive determination of HIV-1 in a
      homogeneous solution has been developed using an electrochemical molecular beacon
      combined with a nafion-graphene composite film modified screen-printed carbon
      electrode (nafion-graphene/SPCE). The electrochemical molecular beacon (CAs-MB),
      comprising a special recognition sequence for the conserved region of the HIV-1
      gag gene and a pair of carminic acid molecules as a marker, can indicate the
      presence of the HIV-1 target by its on/off electrochemical signal behavior. It is
      suitable for direct, electrochemical determination of HIV-1, thereby simplifying
      the detection procedure and improving the signal-to-noise (S/N) ratio. To further
      improve the sensitivity, the nafion-graphene/SPCE was used to monitor changes in
      the CAs-MB, which has notable advantages, such as being ultrasensitive,
      inexpensive, and disposable. Under optimized conditions, the peak currents showed
      a linear relationship with the logarithm of target oligonucleotide concentrations
      ranging from 40 nM to 2.56 MUM, with a detection limit of 5 nM (S/N=3). This
      sensing assay also displays a good stability, with a recovery of 88-106.8% and
      RSD<7% (n=5) in real serum samples. This work may lead to the development of an
      effective method for early point-of-care diagnosis of HIV-1 infection.

PMID- 24099876
TI  - Highly immunostimulatory RNA derived from a Sendai virus defective viral genome.
AB  - Defective viral genomes (DVGs) are generated during virus replication. DVGs
      bearing complementary ends are strong inducers of dendritic cell (DC) maturation
      and of the expression of antiviral and pro-inflammatory cytokines by triggering
      signaling of the RIG-I family of intracellular pattern recognition receptors. Our
      data show that DCs stimulated with virus containing DVGs have an enhanced ability
      to activate human T cells and can induce adaptive immunity in mice. In addition,
      we describe the generation of a short Sendai virus (SeV)-derived DVG RNA (DVG
      324) that maintains strong immunostimulatory activity in vitro and in vivo. DVG
      324 induced high levels of Ifnb expression when transfected into cells and
      triggered fast expression of pro-inflammatory cytokines and mobilization of
      dendritic cells when injected into the footpad of mice. Importantly, DVG-324
      enhanced the production of antibodies to a prototypic vaccine after a single
      intramuscular immunization in mice. Notably, the pro-inflammatory cytokine
      profile induced by DVG-324 was different from that induced by poly I:C, the only
      viral RNA analog currently used as an immunostimulant in vivo, suggesting a
      distinct mechanism of action. SeV-derived oligonucleotides represent novel
      alternatives to be harnessed as potent adjuvants for vaccination. 

PMID- 24099878
TI  - The association between physical activity, cardiorespiratory fitness and self
      rated health.
AB  - OBJECTIVE: To investigate the joint association between self-reported physical
      activity as well as cardiorespiratory fitness and self-rated health among healthy
      women and men. METHOD: Data from 10,416 participants in The Danish Health
      Examination Survey 2007-2008 which took part in 13 Danish municipalities were
      analyzed. Leisure time physical activity level and self-rated health were based
      on self-reported questionnaire data. Optimal self-rated health was defined as
      "very good" or "good" self-rated health. Cardiorespiratory fitness (mL O2.min(
      1).kg(-1)) was estimated from maximal power output in a maximal cycle exercise
      test. RESULTS: A strong dose-response relation between cardiorespiratory fitness
      and self-rated health as well as between physical activity level and self-rated
      health among both women and men was found. Within categories of physical
      activity, odds ratios for optimal self-rated health increased with increasing
      categories of cardiorespiratory fitness, and vice versa. Hence, participants who
      were moderately/vigorously physically active and had a high cardiorespiratory
      fitness had the highest odds ratio for optimal self-rated health compared with
      sedentary participants with low cardiorespiratory fitness (odds ratio=12.2, 95%
      confidence interval: 9.3-16.1). CONCLUSION: Although reluctant to conclude on
      causality, this study suggests that an active lifestyle as well as good
      cardiorespiratory fitness probably increase self-rated health.

PMID- 24099879
TI  - Short sleep duration as a risk factor for the development of the metabolic
      syndrome in adults.
AB  - OBJECTIVE: The objective of this study was to investigate the association between
      self-reported sleep duration and the incidence of features of the metabolic
      syndrome in adults. METHODS: A longitudinal analysis from the Quebec Family Study
      (Canada) was conducted on 293 participants, aged 18 to 65 years, followed for a
      mean of 6 years (until 2001). Participants were categorized as short (<=6 h),
      adequate (7-8 h) or long (>=9 h) sleepers. The metabolic syndrome was defined
      according to the American Heart Association/National Heart, Lung, and Blood
      Institute's criteria. The hypertriglyceridemic waist phenotype was defined as
      high waist circumference (>=90 cm in men and >=85 cm in women) combined with high
      fasting triglyceride level (>=2.0 mmol/L in men and >=1.5 mmol/L in women).
      RESULTS: The incidence rates of metabolic syndrome and hypertriglyceridemic waist
      phenotype were 9.9% and 7.5%, respectively. Short sleepers were significantly
      more at risk of developing the metabolic syndrome (relative risk (RR): 1.74; 95%
      confidence interval (CI): 1.05-2.72) and the hypertriglyceridemic waist phenotype
      (RR: 1.82; 95% CI: 1.16-2.79), compared to those sleeping 7 to 8h per night after
      adjusting for covariates. However, long sleep duration was not associated with an
      increased risk of developing the metabolic syndrome or the hypertriglyceridemic
      waist phenotype (either unadjusted or adjusted models). CONCLUSION: Short sleep
      duration is associated with an increased risk of developing features of the
      metabolic syndrome in adults.

PMID- 24099880
TI  - A novel method of detecting alpha-1 antitrypsin deficiency of Z mutant
      (GAG(342)AAG) in a single PCR reaction using base-quenched probe.
AB  - BACKGROUND: Alpha-1 antitrypsin (A1AT) is a protease inhibitor that protects the
      tissues from degradation by neutrophil elastase under certain pathological
      process. Alpha-1 antitrypsin deficiency (A1ATD) could associate with both lung
      and liver pathogenicities. Of all the deficiency alleles, Z mutant is the most
      common variant and causes severe complications. Here, we described a novel and
      quick method to detect Z mutant using the base-quenched probe technique in only
      one single PCR reaction. METHODS: Primers and probe were designed based on the
      base-quenched probe technique. Two vectors, representing the two genotypes, were
      constructed as amplification templates for validating the method. The Z mutant
      (GAG(342)AAG) was analyzed according to the melting curve. Finally, the accuracy
      was confirmed by direct sequencing. RESULTS: Z mutant could be accurately
      distinguished from the wild type. The wild type resulted in high melting
      temperature (TM) (48.64+/-1.33 degrees C), while when the Z mutation was present,
      the TM was shifted to an obvious low TM (41.38+/-0.9017 degrees C). The
      sensitivity reached a low of 10(3) copies of template DNA with a clear melting
      valley and a complete concordance occurred between this method and the direct DNA
      sequencing. CONCLUSION: The present described method is simple, quick and
      economic as well as suitable for large-scale genotyping studies and clinical
      testing of Z mutant in patients with emphysema and cirrhosis.

PMID- 24099881
TI  - High plasma adiponectin levels in patients with severe traumatic brain injury.
AB  - BACKGROUND: Adiponectin plays an important role in the regulation of tissue
      inflammation. There is a paucity of data on circulating plasma adiponectin
      concentrations in human traumatic brain injury. This study is designed to
      investigate the potential associations between plasma adiponectin levels and
      clinical outcomes after traumatic brain injury. METHODS: Plasma adiponectin
      levels of 86 patients with severe traumatic brain injury and 86 healthy subjects
      were determined. Clinical outcomes included in-hospital mortality, 6-month
      mortality and 6-month unfavorable outcome (Glasgow Outcome Scale score of 1-3).
      RESULTS: Plasma adiponectin levels were significantly higher in patients compared
      to controls (20.5+/-5.9 vs. 7.7+/-2.0MUg/ml; P<0.001) and emerged as an
      independent predictor of in-hospital mortality [odds ratio (OR), 1.318; 95%
      confidence interval (CI), 1.049-1.629; P=0.008], 6-month mortality (OR, 1.328;
      95% CI, 1.082-1.657; P=0.007) and 6-month unfavorable outcome (OR, 1.240; 95% CI,
      1.066-1.443; P=0.005) in a multivariate analysis. For predicting these clinical
      outcomes, areas under receiver operating characteristic curve of plasma
      adiponectin level were similar to those of Glasgow Coma scale scores (all
      P>0.05). However, adiponectin did not improve predictive values of Glasgow Coma
      scale scores (all P>0.05). CONCLUSION: Plasma adiponectin level may represent a
      novel biomarker for predicting clinical outcomes of traumatic brain injury.

PMID- 24099882
TI  - 3D ultrasound system to investigate intraventricular hemorrhage in preterm
      neonates.
AB  - Intraventricular hemorrhage (IVH) is a common disorder among preterm neonates
      that is routinely diagnosed and monitored by 2D cranial ultrasound (US). The
      cerebral ventricles of patients with IVH often have a period of ventricular
      dilation (ventriculomegaly). This initial increase in ventricle size can either
      spontaneously resolve, which often shows clinically as a period of stabilization
      in ventricle size and eventual decline back towards a more normal size, or
      progressive ventricular dilation that does not stabilize and which may require
      interventional therapy to reduce symptoms relating to increased intracranial
      pressure. To improve the characterization of ventricle dilation, we developed a
      3D US imaging system that can be used with a conventional clinical US scanner to
      image the ventricular system of preterm neonates at risk of ventriculomegaly. A
      motorized transducer housing was designed specifically for hand-held use inside
      an incubator using a transducer commonly used for cranial 2D US scans. This
      system was validated using geometric phantoms, US/MRI compatible ventricle volume
      phantoms, and patient images to determine 3D reconstruction accuracy and inter-
      and intra-observer volume estimation variability. 3D US geometric reconstruction
      was found to be accurate with an error of <0.2%. Measured volumes of a US/MRI
      compatible ventricle-like phantom were within 5% of gold standard water
      displacement measurements. Intra-class correlation for the three observers was
      0.97, showing very high agreement between observers. The coefficient of variation
      was between 1.8-6.3% for repeated segmentations of the same patient. The minimum
      detectable difference was calculated to be 0.63 cm(3) for a single observer.
      Results from ANOVA for three observers segmenting three patients of IVH grade II
      did not show any significant differences (p > 0.05) for the measured ventricle
      volumes between observers. This 3D US system can reliably produce 3D US images of
      the neonatal ventricular system. There is the potential to use this system to
      monitor the progression of ventriculomegaly over time in patients with IVH. 

PMID- 24099883
TI  - Development and validation of the Specific Loss of Interest and Pleasure Scale
      (SLIPS).
AB  - BACKGROUND: Anhedonia, or loss of pleasure and/or interest in people or things,
      is a key component of many forms of psychopathology. Extant anhedonia measures
      only assess current state or longstanding trait anhedonia, which risks
      discounting recent changes. Thus, we created the Specific Loss of Interest and
      Pleasure Scale (SLIPS), to assess recent changes in anhedonia. METHODS: Four
      studies assessed the reliability and validity of the SLIPS through factor and
      internal consistency analyses, convergent and divergent validity analyses, and
      incremental validity analyses in individuals reporting non-clinical and clinical
      levels of psychopathology. RESULTS: The SLIPS was internally consistent,
      converged with existing state measures of anhedonia and depression, and diverged
      from general measures of affect and trait anticipatory and consummatory pleasure.
      Furthermore, the SLIPS predicted recent changes in anhedonia independent of
      existing measures. Moreover, in respondents reporting moderate or severe symptoms
      of depression, only the SLIPS was associated with recent changes in anhedonia.
      LIMITATIONS: Prospective limitations included a resulting one factor solution and
      the potential that the method of scaling influenced results. However, these
      limitations were offset by empirical verification and the unique strength of the
      scaling of the SLIPS. CONCLUSIONS: The SLIPS is the first validated measure that
      allows for the assessment of recent changes in anhedonia in non-clinical and
      clinical samples. Results suggest that the SLIPS offers unique clinical utility
      by discriminating changes in anhedonia within at-risk and clinically depressed
      groups.

PMID- 24099884
TI  - Treatment adherence in bipolar I and schizoaffective disorder, bipolar type.
AB  - BACKGROUND: Poor adherence rates in Bipolar Disorder type I (BDI) and
      Schizoaffective Disorder, bipolar type (SAD) may be high This study was aimed at
      comparing the clinical correlates of adherence to treatment and the course of
      illness in BDI and SAD patients. METHODS: 75 SAD and 150 BDI DSM-IV outpatients
      were included. Adherence was assessed on the basis of patients' and care-givers'
      reports and serum levels, when available. Socio-demographic, clinical and
      treatment variables were collected and compared between diagnostic subsamples and
      then between goodly and poorly adherent patients. Multiple logistic regressions
      were performed, controlling for diagnostic subsample differences, to identify
      correlates of adherence in BDI and SAD groups. RESULTS: Poor adherence was highly
      prevalent both in BDI (32%) and in SAD patients (44%), with no significant
      differences between diagnostic categories. Presence of psychotic symptoms
      (p=0.029), higher number of manic relapses (p<0.001), comorbidity with
      personality disorders (p=0.002), and lithium therapy (p=0.003) were associated
      with poor adherence to treatment. Diagnostic subgroup analyses showed different
      predictive models, with the BDI poorly adherent subsample being more likely to
      include comorbid personality and manic recurrences and the SAD poorly adherent
      subsample being less clinically predictable. LIMITATIONS: The cross-sectional
      nature of the study limits de capacity to ascertain the direction of the
      relationship between certain variables. CONCLUSIONS: Rates of poor adherence to
      oral treatments are similar in SAD and BDI. BDI patients with comorbid
      personality and substance use disorders are likely to be poorly adherent.
      Treatment adherence may be more difficult to predict in SAD patients.

PMID- 24099885
TI  - Tall P waves associated with severe hypokalemia and combined electrolyte
      depletion.
AB  - A 32-year-old woman with anorexia nervosa showing tall P waves on
      electrocardiogram (ECG) was reported. Her ECG showed tall P waves (5.5mm in
      voltage, lead II) at 2.2mEq/L of serum potassium. After the treatment, P waves
      decreased in voltage with the normalization of serum potassium. Tall P waves may
      be considered to be the so-called pseudo-P pulmonale, and added to the criteria
      of hypokalemia on ECG. 

PMID- 24099886
TI  - Variegated left ventricular electrical activation in response to a novel
      quadripolar electrode: visualization by non-invasive electrocardiographic
      imaging.
AB  - Improving response to cardiac resynchronization therapy (CRT) remains
      challenging. Appropriate candidates may be identified by the presence of left
      ventricular (LV) conduction delay. An additional determinant may be the
      electrical effect elicited by LV pacing, which may vary among and within
      individuals. However, this is little explored, reflecting the lack of means for
      both easily altering lead position in any individual patient and of rapidly
      assessing its electrical effects. However, the advent of both multipolar LV
      electrodes and non-invasive single-beat electroanatomic mapping potentially
      resolves these challenges. These were investigated here. Results confirmed wide
      variations in electrical responses to LV pacing. In any individual patient,
      different pacing configurations elicited different electrical effects.
      Conversely, any one stimulation vector produced different effects in different
      patients. Thus, the reaction of electrical substrate to LV pacing is
      inconsistent. This observation introduces an added level of complexity in the
      understanding CRT electrical action. Attention to this factor may influence
      response to electrical resynchronization therapy. 

PMID- 24099887
TI  - Visual transform applications for estimating the spatial QRS-T angle from the
      conventional 12-lead ECG: Kors is still most Frank.
AB  - BACKGROUND: The 12-lead ECG-derived spatial QRS-T angle has prognostic and
      diagnostic utility, but most ECG machines currently fail to report it. The
      primary goal was to determine if reasonably accurate methods exist for rapid
      visual estimations of the spatial peaks QRS-T angle from conventional 12-lead ECG
      tracings. METHODS AND RESULTS: Simultaneous 12-lead and Frank XYZ-lead recordings
      were obtained from a publicly available database for 100 post-myocardial
      infarction patients and 50 controls. ANOVA, Pearson's correlation coefficients
      and concordance plots were used to evaluate agreement for spatial peaks QRS-T
      angle results from the true Frank leads versus from several visually applied 12
      to-Frank XYZ-lead transforms. The latter included Kors et al.'s regression and
      quasi-orthogonal, Bjerle and Arvedson's quasi-orthogonal, Dower's inverse, and
      Hyttinen et al.'s, Dawson et al.'s and Guillem et al.'s transforms. Spatial peaks
      QRS-T angles derived from the true Frank leads were not statistically
      significantly different from those derived from any visually applied transform.
      Of the visually applied transforms, the Kors' regression and Kors' quasi
      orthogonal yielded the highest Pearson correlation coefficients against the gold
      standard true Frank lead results [0.84 and 0.77, respectively, when individuals
      with bundle branch blocks were included (N=150), and 0.88 and 0.80, respectively,
      when individuals with bundle branch blocks were excluded (N=137)]. Bland-Altman
      95% confidence intervals showed similar results, with the two Kors'-related
      methods also having the narrowest confidence intervals. CONCLUSIONS: When
      visually applied, the Kors' regression-related and quasi-orthogonal transforms
      allow for reasonably precise spatial peaks QRS-T estimates and thus a potentially
      practical way to visually estimate spatial peaks QRS-T angles from conventional
      12-lead ECGs.

PMID- 24099888
TI  - Endoscopic ultrasound-guided transmural drainage of postoperative pancreatic
      collections.
AB  - BACKGROUND: Pancreatic leak is a major cause of morbidity after pancreatectomy.
      Traditionally, peripancreatic fluid collections have been managed by percutaneous
      or operative drainage. Data for endoscopic ultrasound (EUS)-guided drainage of
      postoperative fluid collections are limited. Here we report on the safety,
      efficacy, and timing of EUS-guided drainage of postoperative peripancreatic
      collections. STUDY DESIGN: This is a retrospective review of 31 patients who
      underwent EUS-guided drainage of fluid collections after pancreatic resection.
      Technical success was defined as successful transgastric deployment of at least
      one double pigtail plastic stent. Clinical success was defined as resolution of
      the fluid collection on follow-up CT scan and resolution of symptoms. Early
      drainage was defined as initial transmural stent placement within 30 days after
      surgery. RESULTS: Endoscopic ultrasound-guided drainage was performed effectively
      with a technical success rate of 100%. Clinical success was achieved in 29 of 31
      patients (93%). Nineteen of the 29 patients (65%) had complete resolution of
      their symptoms and collection with the first endoscopic procedure. Repeat
      drainage procedures, including some with necrosectomy, were required in the
      remaining 10 patients, with eventual resolution of collection and symptoms. Two
      patients who did not achieve durable clinical success required percutaneous
      drainage by interventional radiology. Seventeen (55%) of 31 patients had
      successful early drainage completed within 30 days of their operation.
      CONCLUSIONS: Endoscopic ultrasound-guided drainage of fluid collections after
      pancreatic resection is safe and effective. Early drainage (<30 days) of
      postoperative pancreatic fluid collections was not associated with increased
      complications in this series.

PMID- 24099890
TI  - The intraspecific genetic variability of siliceous and calcareous Gentiana
      species is shaped by contrasting demographic and re-colonization processes.
AB  - The Ciminalis section of Gentiana comprises seven species, two of them growing on
      siliceous substrates (G. alpina and G. acaulis), the other ones being calcareous
      taxa (G. clusii, G. angustifolia, G. ligustica, G. occidentalis and G. dinarica).
      A total of 515 individuals from 183 populations over the entire Ciminalis
      distribution range was analyzed using four chloroplast loci (trnH-psbA, matK,
      rpoB and rpoC1) and the nuclear ribosomal marker ITS2. The siliceous species
      display only two chloroplast haplotypes each and are both characterized by
      patterns of range expansions all over the Alps. Conversely, the calcareous
      species are on average more diverse (two to 13 haplotypes per species) with
      strong patterns of local structuring. We suggest that the occurrence of many
      calcareous refugia at the periphery of the Alps must have led to local adaptation
      and morphological diversification, and helped preserving intraspecific
      diversities during the last glaciations for the associated taxa. ITS2 was more
      efficient in delineating species boundaries than the chloroplast markers for
      which several haplotypes are shared among species. This might be either due to
      chloroplast capture among species and/or to recent divergence. Species adapted to
      the same substrate are generally only distantly related when they co-occur in the
      same place. For both types of markers, G. clusii is found genetically distant
      from all other species. 

PMID- 24099889
TI  - Molecular phylogeny reveals independent origins of body scales in Entomobryidae
      (Hexapoda: Collembola).
AB  - Entomobryidae is the largest family in Collembola but relationships within the
      family have never been subjected to rigorous phylogenetic analyses. Within the
      family, body scales are present in many species, and are fundamental in the
      classification at the subfamilial and tribal levels. A molecular phylogeny was
      reconstructed using the nuclear 18SrRNA and partial 28SrRNA and the mitochondrial
      16SrRNA to examine the evolution of scales across Entomobryidae subfamilies.
      These datasets were analyzed separately and combined, with parsimony, likelihood
      and Bayesian algorithms. Monophyly of Orchesellinae was not recovered, and it was
      split into a scaled clade and an unscaled clade, contradicting to all recent
      taxonomic conceptions. The monophyly of Entomobryinae, Seirinae and
      Lepidocyrtinae is well supported however within Entomobryinae, the polyphyly of
      Entomobryini and Willowsiini implies that classification using the
      presence/absence of scales is not valid. Analyses of ancestral character state
      reconstruction in Entomobryidae indicate that the presence of body scales have
      evolved independently at least five times, with a loss of scales occurring
      independently at least twice. A revision of the family Entomobryidae on molecular
      and morphological basis is clearly needed. 

PMID- 24099891
TI  - Lymphocyte subsets in experimental rhinovirus infection in chronic obstructive
      pulmonary disease.
AB  - BACKGROUND: COPD is associated with increased numbers of T cells in the lungs,
      particularly CD8+ T cells. The mechanisms of increased T cells are unknown but
      may be related to repeated virus infections in COPD patients. We analysed
      lymphocyte subsets in blood and bronchoalveolar lavage in smokers and COPD
      subjects during experimental rhinovirus infections. METHODS: Lymphocytes were
      isolated from blood and bronchoalveolar lavage from COPD subjects and non
      obstructed smokers prior to, and following experimental rhinovirus infection.
      Lymphocyte surface markers and intracellular cytokines were analysed using flow
      cytometry. RESULTS: Following rhinovirus infection CD4+ and CD8+ T cell numbers
      in the COPD subjects were significantly reduced in blood and CD3+ and CD8+ T
      cells increased in bronchoalveolar lavage compared to baseline. T cells did not
      increase in BAL in the control subjects. CD3+ T cells correlated with virus load.
      CONCLUSIONS: Following rhinovirus infection T cells move from the circulation to
      the lung. Repeated virus infections may contribute to T cell accumulation in COPD
      patients.

PMID- 24099892
TI  - Normative feedback for parents of college students: piloting a parent based
      intervention to correct misperceptions of students' alcohol use and other
      parents' approval of drinking.
AB  - OBJECTIVE: Multi-component parent-based interventions (PBIs) provide a promising
      avenue for targeting alcohol use and related consequences in college students.
      Parents of college-aged children can have a significant influence on their
      children's alcohol use decisions. However, parents tend to underestimate their
      own child's alcohol use and overestimate other similar parents' approval of
      student drinking. These misperceptions could have important implications for
      parents' own attitudes and alcohol-related communication with their student.
      Targeting these misperceptions through normative feedback could help promote
      greater and more in-depth alcohol-related communication. The present study
      examines the potential efficacy of web-based alcohol-related normative feedback
      for parents of college students. METHOD: A sample of 144 parents of college
      students received web-based normative feedback about students' alcohol use and
      approval, as well as other same-college parents' alcohol approval. Parents
      completed measures of perceived student alcohol use, student alcohol approval,
      other-parent alcohol approval, and intentions to discuss alcohol use both pre-
      and post-normative feedback. RESULTS: Post-feedback, parents reported stronger
      intentions to talk to their student about alcohol, were less confident in their
      knowledge of their students' alcohol use, and believed that their student drank
      in greater quantity and more frequently than pre-feedback. Parents also perceived
      other parents to be less approving of alcohol use after viewing normative
      feedback. CONCLUSIONS: These findings provide preliminary support for the use of
      web-based normative feedback for parents of college students. Given these
      promising results, further research developing and testing this approach merits
      attention.

PMID- 24099893
TI  - A randomized, double-blind, placebo-controlled study of fentanyl buccal tablets
      for breakthrough pain: efficacy and safety in Japanese cancer patients.
AB  - CONTEXT: Rapid-onset opioids for treating breakthrough pain (BTP) in patients
      with cancer are needed in the Japanese care setting. OBJECTIVES: To examine the
      efficacy and safety of fentanyl buccal tablets (FBTs) for treating BTP in
      Japanese cancer patients. METHODS: This was a randomized, double-blinded, placebo
      controlled study. In subjects receiving around-the-clock (ATC) opioids at doses
      of 30 mg or more to less than 60 mg or 60-1000 mg of oral morphine equivalents
      (low and high ATC groups), dose titration was started from 50 to 100 MUg FBT,
      respectively. Subjects whose effective dose was identified were randomly
      allocated to a prearranged administration order of nine tablets (six FBTs and
      three placebos), one tablet each for nine episodes of BTP (double blinded).
      Efficacy and safety of FBT were assessed for patients overall, and also for the
      low and high ATC groups. RESULTS: A significant difference was observed between
      FBT and placebo for the primary endpoint of pain intensity difference at 30
      minutes. The analgesic onset of FBT was observed from 15 minutes in several
      secondary variables (e.g., pain relief). Adverse events were somnolence and other
      events associated with opioids were mostly mild or moderate. Of the low and high
      ATC group subjects, an effective FBT dose was identified in 72.2% and 73.1%,
      respectively. CONCLUSION: The safety of FBT and its analgesic effect on BTP were
      confirmed in Japanese cancer patients receiving opioids. Our findings suggest
      that analgesic onset may occur from 15 minutes after FBT, and that FBT can be
      administered to patients with low doses of ATC opioids.

PMID- 24099895
TI  - Dignity in care: time to take action.
AB  - Providing care for patients and caring about patients should go hand in hand.
      Caring implicates our fundamental attitude towards patients, and our ability to
      convey kindness, compassion and respect. Yet all too often, patients and families
      experience health care as impersonal, mechanical; and quickly discover that
      patienthood trumps personhood. The consequences of a medical system organized
      around care rather than caring are considerable. Despite technical competence,
      patients and families are less satisfied with medical encounters when caring is
      lacking. Lack of empathy and emotional disengagement from patients typifies
      health care provider burnout. Caring is the gateway to disclosure; without it,
      patients are less likely to say what is bothering them, leading to missed
      diagnoses, medical errors and compromised patient safety. There are also
      liability issues, with most complaints levied against health care professionals
      stemming from failures in care tenor. Formal education for health care providers
      lacks a continued focus on achieving a culture of caring. If caring really
      matters, health care systems can insist on certain behaviors and impose certain
      obligations on health care providers to improve care tenor, empathy, and
      effective communication. Caregivers need to be engaged in looking at their own
      attitudes towards patients, their own vulnerability, their own fears and whatever
      else it is that shapes their tone of care. Health care professionals must set
      aside some time, supported by their institutions, to advance a culture of caring
      now is the time to take action. 

PMID- 24099894
TI  - Clinical trial participation as part of end-of-life cancer care: associations
      with medical care and quality of life near death.
AB  - CONTEXT: Clinical trials are a common therapeutic option for patients with
      advanced incurable cancer. OBJECTIVES: To examine the associations between trial
      participation and end-of-life (EOL) outcomes, including aggressive care and
      quality of life (QOL). METHODS: Coping with Cancer, a multicenter prospective
      cohort study of patients with metastatic cancer, progressed after at least first
      line chemotherapy. Baseline chart review documented clinical trial participation.
      Baseline interviews assessed psychosocial characteristics and EOL preferences.
      Caregiver interview and chart review assessed medical care and QOL near death.
      The primary outcome was aggressive EOL care (ventilation, resuscitation, or
      intensive care unit admission in last week of life). Propensity score weighting
      balanced patient characteristics that differed by trial participation, including
      care preferences and EOL discussion. Propensity score-weighted regression models
      estimated the effect of trial participation on outcomes. RESULTS: Of 352 patients
      followed to death, 37 were enrolled in a clinical trial at baseline. In
      propensity score-weighted analyses, trial participation was significantly
      associated with aggressive EOL care (21.6% vs. 12.0%, adjusted odds ratio [AOR]
      2.04, 95% confidence interval [CI] 1.00-4.15), late hospice enrollment (51.4% vs.
      42.2%, AOR 1.96, 95% CI 1.10-3.50), hospital death (48.6% vs. 25.7%, AOR 2.74,
      95% CI 1.37-5.47), intensive care unit death (16.2% vs. 6.3%, AOR 3.53, 95% CI
      1.29-9.65), and inferior QOL near death (least squares mean 5.93 vs. 7.69,
      P<0.001). Controlling for EOL care, trial enrollment was no longer associated
      with QOL near death (P=0.342). CONCLUSION: Clinical trial participation is
      associated with aggressive EOL care. Aggressive EOL care appears to explain the
      association between trial participation and QOL near death.

PMID- 24099896
TI  - Palliative sedation in patients with advanced cancer followed at home: a
      prospective study.
AB  - CONTEXT: Home care programs in Italy. OBJECTIVES: The aim of this study was to
      assess a protocol for palliative sedation (PS) performed at home. METHODS: A
      total of 219 patients were prospectively assessed to evaluate a PS protocol in
      patients with advanced cancer followed at home by two home care programs with
      different territorial facilities. The protocol was based on stepwise
      administration of midazolam. RESULTS: A total of 176 of the patients died at
      home, and PS was performed in 24 of these patients (13.6%). Younger patients
      received the procedure more frequently than older patients (P=0.012). The
      principal reasons to start PS were agitated delirium (n=20) and dyspnea (n=4).
      Mean duration of PS was 42.2+/-30.4 hours, and the mean doses of midazolam were
      23-58 mg/day. Both the home care team and the patients' relatives expressed
      optimal or good levels of satisfaction with the procedure in all but one case,
      respectively. CONCLUSION: This protocol for PS was feasible and effective in
      minimizing distress for a subgroup of patients who died at home. The
      characteristics of patients who may be effectively sedated at home should be
      better explored in future studies.

PMID- 24099897
TI  - Development and validation of a new tool for the assessment and spiritual care of
      palliative care patients.
AB  - CONTEXT: Spiritual assessment tools and interventions based on holistic
      approaches are needed to promote healing. Such tools must be adapted to the wide
      cultural backgrounds of contemporary Western society. OBJECTIVES: To develop and
      validate a new brief measure, simultaneously featuring clinical applicability and
      adequate psychometric properties. The tool uses six initial questions to
      establish a climate of trust with patients before they complete an eight-item,
      five-point Likert scale. The questionnaire is based on a model of spirituality
      generated by the Spanish Society of Palliative Care (SECPAL) Task Force on
      Spiritual Care (Grupo de Espiritualidad de la SECPAL), which aims to recognize,
      share, and assess the spiritual resources and needs of palliative care patients.
      METHODS: Multidisciplinary professionals from 15 palliative care teams across
      Spain interviewed 108 patients using the Grupo de Espiritualidad de la SECPAL
      questionnaire. Confirmatory factor analysis techniques were used to study the new
      tool factor structure and reliability. Additionally, concurrent criterion
      validity coefficients were estimated considering spiritual well-being, anxiety,
      depression, resilience, and symptoms. Descriptive statistics on questionnaire
      applicability were reported. RESULTS: Analyses supported a three-factor structure
      (intrapersonal, interpersonal, transpersonal) with an underlying second-order
      factor representing a spirituality construct. Adequate reliability results and
      evidence for construct validity were obtained. CONCLUSION: The new questionnaire,
      based on empirical research and bedside experience, showed good psychometric
      properties and clinical applicability.

PMID- 24099898
TI  - Assessing acute toxicity potential of persulfate ISCO treated water.
AB  - Persulfate anion (S2O8(2-)), a widely used in situ chemical oxidation agent, is
      increasingly applied for environmental remediation. However, limited information
      on environmental and toxicological effects is available for the evaluation of the
      environmental risk of exposure to S2O8(2-), particularly after its application.
      In this study, the acute toxic effects on the common carp (Cyprinus carpio) were
      employed as a model to investigate S2O8(2-), sulfate ion (decomposition product
      of S2O8(2-)), hydrogen/hydroxide ions and also the mixtures of these ion species.
      Acute toxicity test results showed 96h median lethal concentrations (LC50) of
      540+/-23mgL(-1) for S2O8(2-) and 4100+/-110mgL(-1) for SO4(2-). S2O8(2-) was
      considerably more toxic than its decomposition product SO4(2-). Additionally,
      solution pH was also an important factor influencing toxicity, and S2O8(2-) posed
      reduced acute toxicity when pH was in the range of 6-10. Water conductivity up to
      approximately 8000MUScm(-1) did not appear to significantly increase fish
      mortality. In the mixture toxicity test (i.e., S2O8(2-)/OH(-)), LC50 values of
      130+/-10mgL(-1) for S2O8(2-) and 23+/-2mgL(-1) for OH(-) were lower than those
      obtained from the individual toxicity tests and therefore exhibited higher
      toxicity to fish. However, upon complete decomposition of S2O8(2-) in the
      mixture, a reduction in acute toxicity may be expected. The results of this study
      revealed that it may be necessary and/or desirable to control the residual S2O8(2
      )and pH after S2O8(2-) addition when potential exposure to an aquatic system is a
      concern. 

PMID- 24099899
TI  - SO(2) inhalation causes synaptic injury in rat hippocampus via its derivatives in
      vivo.
AB  - SO(2) remains a common air pollutant, almost half of the world's population uses
      coal and biomass fuels for domestic energy. Limited evidence suggests that
      exposure to SO(2) may be associated with neurotoxicity and increased risk of
      hospitalization and mortality of many brain disorders. However, our understanding
      of the mechanisms by which SO(2) causes harmful insults on neurons remains
      elusive. To explore the molecular mechanism of SO(2)-induced neurotoxic effects
      in hippocampal neurons, we evaluated the synaptic plasticity in rat hippocampus
      after exposure to SO(2)at various concentrations (3.5 and 7 mg m(-3), 6 h d(-1),
      for 90 d) in vivo, and in primary cultured hippocampal neurons (DIV7 and DIV14)
      after the treatment of SO2 derivatives in vitro. The results showed that SYP, PSD
      95, NR-2B, p-ERK1/2 and p-CREB were consistently inhibited by SO(2)/SO(2)
      derivatives in more mature hippocampal neurons in vivo and in vitro, while the
      effects were opposite in young hippocampal neurons. Our results indicated that in
      young neurons, SO(2) exposure produced neuronal insult is similar to ischemic
      injury; while in more mature neurons, SO(2) exposure induced synaptic
      dysfunctions might participate in cognitive impairment. The results implied that
      SO(2) inhalation could cause different neuronal injury during brain development,
      and suggested that the molecular mechanisms might be involved in the changes of
      synaptic plasticity.

PMID- 24099900
TI  - [Geriatric assessment and factors associated with mortality in elderly patients
      with heart failure admitted to an acute geriatric unit].
AB  - INTRODUCTION AND OBJECTIVES: Heart failure (HF) is very prevalent in older
      adults, and is associated with a high mortality. The prediction of the outcome of
      HF and the identification of patients in advanced stages is difficult. The
      present work aims at identifying variables of the geriatric assessment and other
      clinical variables associated with an increased risk of death at one year in
      older adults with HF. MATERIAL AND METHODS: Prospective study of 101 patients
      (mean age, 85.9 +/- 6.3 years, 81% women) admitted during 2006 to an Acute
      Geriatric Unit, with principal diagnosis of HF. We recorded: demographic data,
      predisposing heart disease, main trigger of exacerbation, comorbidity, number of
      prescriptions at discharge and specific treatment of HF, average length-of-stay,
      readmissions, and mortality at one year after discharge. Geriatric assessment
      included: disability in basic (Barthel index) and instrumental (Lawton index)
      activities of daily living, cognitive function (Pfeiffer test), comorbidity
      (Charlson index), and geriatric syndromes. RESULTS: In a multivariable logistic
      regression model, previous disability (lower Barthel index) (OR [95%CI]=1.03
      [1.01-1.06]; P=.040) and higher number of re-admissions (OR [95%CI]=3.53 [1.19
      10.44]; P=.023) were associated with 1-year mortality. Female sex had a
      protective effect (OR [95%CI]=0.15 [0.04-0.59]; P=.007). CONCLUSIONS: Disability
      in the basic activities of daily living and re-admissions were associated with
      increased 1-year mortality in older adults, whereas female sex was protective. If
      confirmed in further studies, these data could reinforce the need for a
      systematic comprehensive geriatric assessment in older adults with HF.

PMID- 24099901
TI  - [Posterior reversible encephalopathy syndrome. Presentation of a case in a frail
      elderly woman].

PMID- 24099902
TI  - [Proton bomb inhibitors: a study of the prescription in a functional recovery
      unit].
AB  - INTRODUCTION: The use of proton pump inhibitors (PPI) has increased exponentially
      since they were introduced. However concerns have been raised regarding the
      appropriateness of these prescriptions, and the potential side effects,
      particularly in frail elderly people, as well as the cost of this treatment. The
      aim of this study was to assess the extent and appropriateness of PPI prescribing
      in a group of patients over 65 years old admitted to the functional recovery unit
      of a medium-stay hospital. MATERIALS AND METHODS: A retrospective review of
      inpatient prescribing of PPI was carried out in a functional recovery unit in
      Hospital de la Fuenfria, selecting those older than 65 years, who were admitted
      during 2011. Data obtained from medical records included, prescription of a PPI
      before admission and at the time of discharge from hospital (both acute care
      hospital and Hospital de la Fuenfria), type of PPI, and indications for their
      prescription. RESULTS: Inclusion criteria were met by 296 patients (mean age 78.8
      years, 70.6% females). A total of 45.3, 79.1 and 75.5% of patients were on PPIs
      before admission, and at the time of being discharge from acute care hospital,
      and Hospital de la Fuenfria, respectively. A valid indication for therapy was not
      apparent in 62.7, 30.8 and 54.2% of them. Omeprazole was the most widely
      prescribed PPI. CONCLUSIONS: There appears to be a widespread and inappropriate
      use of PPIs in hospital practice. Interventions are needed to curtail this
      inappropriate prescribing practice, avoiding side effects and drug interactions.

PMID- 24099909
TI  - No more fear of the cavernous sinuses!
AB  - After a review of the anatomy of the cavernous sinuses (CS), this work presents
      the clinical picture and imaging protocol of lesions which occur in this area. It
      outlines extension and imaging features of these lesions. It emphasises MRI
      appearance, such as T1, T2 and diffusion signal, type of contrast medium uptake.
      A complementary CT scan is performed if an associated abnormality of the base of
      the skull is suspected on MRI (lysis, condensation). This paper proposes a
      straightforward classification system depending on imaging and sets out the
      principal symptoms of the main aetiologies of CS lesions which are represented by
      various diseases such as tumours, inflammations, vascular abnormalities.
      Complementary to imaging, their diagnosis is based on clinical data i.e. known
      cancer, signs suggesting inflammation. Its rich iconography allows this article
      to be used as a reference in current clinical practice. 

PMID- 24099908
TI  - High gamma power in ECoG reflects cortical electrical stimulation effects on unit
      activity in layers V/VI.
AB  - OBJECTIVE: Cortical electrical stimulation (CES) has been used extensively in
      experimental neuroscience to modulate neuronal or behavioral activity, which has
      led this technique to be considered in neurorehabilitation. Because the cortex
      and the surrounding anatomy have irregular geometries as well as inhomogeneous
      and anisotropic electrical properties, the mechanism by which CES has therapeutic
      effects is poorly understood. Therapeutic effects of CES can be improved by
      optimizing the stimulation parameters based on the effects of various stimulation
      parameters on target brain regions. APPROACH: In this study we have compared the
      effects of CES pulse polarity, frequency, and amplitude on unit activity recorded
      from rat primary motor cortex with the effects on the corresponding local field
      potentials (LFP), and electrocorticograms (ECoG). CES was applied at the surface
      of the cortex and the unit activity and LFPs were recorded using a penetrating
      electrode array, which was implanted below the stimulation site. ECoGs were
      recorded from the vicinity of the stimulation site. MAIN RESULTS: Time-frequency
      analysis of LFPs following CES showed correlation of gamma frequencies with unit
      activity response in all layers. More importantly, high gamma power of ECoG
      signals only correlated with the unit activity in lower layers (V-VI) following
      CES. Time-frequency correlations, which were found between LFPs, ECoGs and unit
      activity, were frequency- and amplitude-dependent. SIGNIFICANCE: The signature of
      the neural activity observed in LFP and ECoG signals provides a better
      understanding of the effects of stimulation on network activity, representative
      of large numbers of neurons responding to stimulation. These results demonstrate
      that the neurorehabilitation and neuroprosthetic applications of CES targeting
      layered cortex can be further improved by using field potential recordings as
      surrogates to unit activity aimed at optimizing stimulation efficacy. Likewise,
      the signatures of unit activity observed as changes in high gamma power in ECoGs
      suggest that future cortical stimulation studies could rely on less invasive
      feedback schemes that incorporate surface stimulation with ECoG reporting of
      stimulation efficacy.

PMID- 24099910
TI  - Dihydroartemisinin induces autophagy by suppressing NF-kappaB activation.
AB  - Nuclear factor-kappa B (NF-kappaB) and autophagy are two major regulators
      involved in both tumor initiation and progression. However, the association
      between these two signaling pathways still remains obscure. In this work, we
      demonstrate that dihydroartemisinin (DHA) stimulates the induction of autophagy
      in several cancer cell lines through repression of NF-kappaB activity. We also
      show that inhibiting NF-kappaB results in an accumulation of reactive oxygen
      species (ROS), which participate in the stimulation of autophagy. These findings
      present a pathway by which DHA promotes autophagy in cancer cells and provide
      evidence for the DHA-induced sensitization effect of some chemotherapeutics. 

PMID- 24099911
TI  - Circadian molecular clocks and cancer.
AB  - Physiological processes such as the sleep-wake cycle, metabolism and hormone
      secretion are controlled by a circadian rhythm adapted to 24h day-night
      periodicity. This circadian synchronisation is in part controlled by ambient
      light decreasing melatonin secretion by the pineal gland and co-ordinated by the
      suprachiasmatic nucleus of the hypothalamus. Peripheral cell autonomous circadian
      clocks controlled by the suprachiasmatic nucleus, the master regulator, exist
      within every cell of the body and are comprised of at least twelve genes. These
      include the basic helix-loop-helix/PAS domain containing transcription factors;
      Clock, BMal1 and Npas2 which activate transcription of the periodic genes (Per1
      and Per2) and cryptochrome genes (Cry1 and Cry2). Points of coupling exist
      between the cellular clock and the cell cycle. Cell cycle genes which are
      affected by the molecular circadian clock include c-Myc, Wee1, cyclin D and p21.
      Therefore the rhythm of the circadian clock and cancer are interlinked. Molecular
      examples exist including activation of Per2 leads to c-myc overexpression and an
      increased tumor incidence. Mice with mutations in Cryptochrome 1 and 2 are
      arrhythmic (lack a circadian rhythm) and arrhythmic mice have a faster rate of
      growth of implanted tumors. Epidemiological finding of relevance include 'The
      Nurses' Health Study' where it was established that women working rotational
      night shifts have an increased incidence of breast cancer. Compounds that affect
      circadian rhythm exist with attendant future therapeutic possibilities. These
      include casein kinase I inhibitors and a candidate small molecule KL001 that
      affects the degradation of cryptochrome. Theoretically the cell cycle and
      malignant disease may be targeted vicariously by selective alteration of the
      cellular molecular clock. 

PMID- 24099912
TI  - Nanosecond pulsed electric fields as a novel drug free therapy for breast cancer:
      an in vivo study.
AB  - Nanosecond pulsed electric fields (nsPEFs) is a novel non-thermal approach to
      induce cell apoptosis. NsPEFs has been proven effective in treating several
      murine tumors, but few studies focus on its efficacy in treating human tumors. To
      determine if nsPEFs is equally effective in treatment of human breast cancer, 30
      human breast cancer tumors across 30Balb/c (nu/nu) mice were exposed to 720
      pulses of 100ns duration, at 4pulsespersecond and 30kV/cm. Two weeks after
      treatment, the growth of treated tumors was inhibited by 79%. Morphological
      changes of tumors were observed via a 3.0T clinical magnetic resonance imaging
      (MRI) system with a self-made surface coil. Pulsed tumors exhibited apoptosis
      evaluated by TUNEL staining, inhibition in Bcl-2 expression and decreased blood
      vessel density. Notably, CD34, vascular endothelial growth factor (VEGF) and VEGF
      receptor (VEGFR) expression in treated tumors were strongly suppressed. To
      evaluate the might-be adverse effects of nsPEFs in healthy tissues, normal skin
      was treated exactly the same way as tumors, and pulsed skin showed no permanent
      damages. The results suggest nsPEFs is able to inhibit human breast cancer
      development and suppress tumor blood vessel growth, indicating nsPEFs may serve
      as a novel therapy for breast cancer in the future. 

PMID- 24099913
TI  - Metadherin regulates metastasis of squamous cell carcinoma of the head and neck
      via AKT signalling pathway-mediated epithelial-mesenchymal transition.
AB  - Our recent study suggested that metadherin (MTDH) is overexpressed in laryngeal
      squamous cell carcinoma. Here, we further investigated its role in promoting
      metastasis of squamous cell carcinoma of the head and neck (SCCHN). An
      immunohistochemistry analysis demonstrated that MTDH is elevated and positively
      correlated with metastasis in 189 primary SCCHN tissues. In vitro experiments
      demonstrated that MTDH overexpression enhanced the migratory and invasive ability
      of SCCHN cells. Moreover, MTDH induced epithelial-mesenchymal transition (EMT) by
      both regulating morphological changes and mediating the expression of the
      biomolecular makers E-cadherin and vimentin. In addition, MTDH mediated AKT
      activation, and all of the above effects were nearly completely blocked by the
      inhibition of AKT. Our results suggested that MTDH might promote the metastasis
      of SCCHN through AKT signalling pathway mediated-EMT. 

PMID- 24099914
TI  - A novel highly reactive Fab antibody for breast cancer tissue diagnostics and
      staging also discriminates a subset of good prognostic triple-negative breast
      cancers.
AB  - The discovery of novel markers for breast cancer (BC) has been recently relied on
      antibody combinatorial libraries and selection through phage display. We
      constructed a recombinant Fab library, and after selections against BC tissues,
      the FabC4 clone was thoroughly investigated by immunohistochemistry in 232
      patients with long-term follow-up. The FabC4 ligand was determined by mass
      spectrometry. The FabC4 expression was associated with younger age, lack of
      progesterone receptor, higher histological grades and non-luminal subtypes, and
      it also identified a subset of good prognostic triple-negative BCs, possibly
      targeting a conformational epitope of Cytokeratin-10 (CK10). This new CK10
      epitope specific antibody may open new possibilities in diagnostic and
      therapeutic strategies. 

PMID- 24099915
TI  - MicroRNA-31 inhibits cisplatin-induced apoptosis in non-small cell lung cancer
      cells by regulating the drug transporter ABCB9.
AB  - Alterations in microRNA (miRNA) expression have been found to be involved in
      tumor growth and response to chemotherapy. However, the possible role of miR-31
      in cisplatin (DDP) resistance in non-small cell lung cancer (NSCLC) remains
      unclear. In this study, we identified a DDP-sensitive and a DDP-resistant cell
      line from four candidate human NSCLC cell lines. Notably, we found that miR-31
      was significantly upregulated in the DDP-resistant cell line compared with its
      level in the DDP-sensitive cell line. As a result, miR-31 overexpression induced
      DDP resistance in the DDP-sensitive cell line, and miR-31 knockdown rescued DDP
      sensitivity in the DDP-resistant cell line. Interestingly, miR-31 was inversely
      correlated with the expression of the drug resistance gene ABCB9. The luciferase
      activity assay showed that miR-31 directly targets the 3'UTR of ABCB9, which is
      known to play a crucial role in drug resistance. Mechanistically, we showed that
      miR-31 confers DDP-induced apoptosis and that inhibition of ABCB9 is required for
      DDP resistance. The data demonstrate that miR-31 exerts an anti-apoptotic effect
      most likely through the inhibition of ABCB9 and thus provide a novel strategy
      involving the use of miR-31 as a potential target in NSCLC chemotherapy. 

PMID- 24099916
TI  - Polymeric micelles containing reversibly phospholipid-modified anti-survivin
      siRNA: a promising strategy to overcome drug resistance in cancer.
AB  - The discovery that survivin, a small anti-apoptotic protein, is involved in
      chemoresistance, opens a new scenario to overcome the drug resistance in cancer.
      It was shown that siRNA can efficiently inhibit the expression of survivin in
      cancer cells. However, the clinical use of siRNA is still hampered by an
      unfavorable pharmacokinetic profile. To address this problem, earlier we
      developed a novel system to deliver siRNA into cancer cells. Namely, we
      reversibly modified the survivin siRNA with a phosphothioethanol (PE) portion via
      a reducible disulfide bond and incorporated the resulting siRNA-S-S-PE conjugate
      into nanosized polyethyelene glycol 2000-phosphatidyl ethanolamine (PEG2000-PE)
      based polymeric micelles (PM), obtaining survivin siRNA PM. The activity of these
      nanopreparations was evaluated by survivin protein down-regulation, tumor cell
      growth inhibition, and chemosensitization of the treated tumor cells to
      paclitaxel (PXL). We found a significant decrease of cell viability and down
      regulation of survivin protein levels after treatment with survivin siRNA PM in
      several cancer cell lines. In addition, the down-regulation of survivin by
      treating cells with survivin siRNA PM, elicited a significant sensitization of
      the cells to PXL, in both sensitive and resistant cancer cell lines. Finally, we
      demonstrated successful co-delivery of PXL and survivin siRNA in the same PM
      leading to superior therapeutic activity compared to their sequential
      administration. Our results support the use of this new platform for the
      treatment of the most aggressive tumors. 

PMID- 24099917
TI  - Identification of a mitotic death signature in cancer cell lines.
AB  - This study examined the molecular mechanism of action of anti-mitotic drugs. The
      hypothesis was tested that death in mitosis occurs through sustained mitotic
      arrest with robust Cdk1 signaling causing complete phosphorylation of Mcl-1 and
      Bcl-xL, and conversely, that mitotic slippage is associated with incomplete
      phosphorylation of Mcl-1/Bcl-xL. The results, obtained from studying six
      different cancer cell lines, strongly support the hypothesis and identify for the
      first time a unique molecular signature for mitotic death. The findings represent
      an important advance in understanding anti-mitotic drug action and provide
      insight into cancer cell susceptibility to such drugs which has important
      clinical implications. 

PMID- 24099918
TI  - Synthesis of surface molecularly imprinted nanoparticles for recognition of
      lysozyme using a metal coordination monomer.
AB  - Molecularly imprinted polymers against proteins are regarded as promising
      substitutes for natural antibodies, but have been frustrated with the problems
      including reduced interaction between functional monomers and protein template in
      the aqueous media required during their synthesis and restricted mass transfer
      across the resulting crosslinked polymer matrixes. For addressing these issues,
      herein we proposed a strategy for imprinting of a protein on the surface of
      nanoparticles using a metal chelating monomer. With lysozyme as a model protein
      template and Cu(2+) chelating N-(4-vinyl)-benzyl iminodiacetic acid as the
      coordination monomer along with other monomers, protein imprinted polymer
      nanoshells were formed over vinyl-modified silica nanoparticles via surface
      polymerization in high-dilution monomer solution. The feed concentration of the
      crosslinking monomer was optimized toward achieving the best imprinting effect.
      Compared with the related imprinted materials reported previously, the resultant
      core-shell imprinted particles showed greatly faster binding kinetics, elevated
      rebinding capacity and selectivity. More importantly, noticeably high binding
      affinity was achieved with an estimated dissociation constant of 4.1 * 10(-8)M
      which is comparable to that of conventional antibodies.

PMID- 24099919
TI  - Increasing occurrence of antimicrobial-resistant hypervirulent (hypermucoviscous)
      Klebsiella pneumoniae isolates in China.
AB  - BACKGROUND: New hypervirulent variants of Klebsiella pneumoniae (hvKP) are
      emerging globally, most of which exhibit antimicrobial susceptibility. METHODS: A
      retrospective study was conducted in 88 patients with cultures positive for K.
      pneumoniae hospitalized in the Beijing You'an Hospital from April 2010 to June
      2012. The clinical and molecular data of the hvKP isolates (defined as string
      test positive) were compared with those of the classic K. pneumoniae (cKP)
      isolates. RESULTS: Overall, 33.0% (29/88) of K. pneumoniae isolates were hvKP.
      Univariate analysis revealed the following risk factors for hvKP: virulence gene
      rmpA (odds ratio [OR], 16.92 [95% confidence interval {CI}, 4.842-59.145]),
      capsule antigens K1 (OR, 3.355 [95% CI, 1.153-9.768]) and K2 (OR, 9.280 [95% CI,
      0.987-87.250]), alcoholic hepatitis (OR, 7.435 [95% CI, 1.397-39.572]), liver
      abscess (OR, 9.068 [95% CI, 1.747-47.061]), metastatic infection (OR, 2.752 [95%
      CI, 1.100-6.886]), community-acquired infection (OR, 10.432 [95% CI, 3.623
      30.033]), sputum isolation (OR, 0.312 [95% CI, .095-1.021]), and HIV infection
      (<0.001 [not applicable]). Multivariate analysis implicated rmpA (OR, 17.398 [95%
      CI, 4.224-71.668]) and community-acquired infection (OR, 6.844 [95% CI, 1.905
      24.585]) as independent risk factors. The proportion of hvKP isolates increased
      from April to December 2010, January to September 2011, and October 2011 to June
      2012 (to 25.5%, 26.7%, and 54.5%, respectively). Resistance to 14 of 19 tested
      antimicrobials was found to be significantly greater in cKP compared to hvKP.
      Importantly, resistance to all the tested antimicrobials, except carbapenems and
      amikacin, was observed in a proportion of hvKP strains, 17% (5/29) of which
      expressed extended-spectrum beta-lactamase. Furthermore, antimicrobial resistance
      in hvKP strains increased over time. CONCLUSIONS: HvKP strains are being isolated
      from patients in China with increasing frequency and constitute an increasing
      proportion of K. pneumoniae strains, indicating an increasing propensity for the
      acquisition of antimicrobial resistance.

PMID- 24099920
TI  - Abnormal patterns of theta frequency oscillations during the temporal evolution
      of freezing of gait in Parkinson's disease.
AB  - OBJECTIVE: We sought to characterize the electrophysiological signature of
      Freezing of gait in Parkinson's disease. METHODS: We examined 24 patients with
      idiopathic Parkinson's disease and significant freezing of gait as they performed
      a series of timed up-and-go tasks in their 'off' state while
      electroencephalographic data was collected from four scalp leads. Fast Fourier
      Transformation was utilized to explore the power spectral density between periods
      of normal walking and periods of freezing, as well as during the transition
      between the two states. In addition, Cross Spectrum and Cross Frequency analyses
      were used to explore the role of impaired temporal and spatial connectivity.
      RESULTS: When compared to walking, episodes of freezing were associated with a
      significant increase in theta band power within the central and frontal leads.
      The transition from normal walking to freezing of gait was also associated with
      increased theta frequency coupling between the central and frontal leads, along
      with an increase in cross-frequency coupling in the central lead. CONCLUSIONS:
      Episodes of freezing of gait in Parkinson's disease are associated with abnormal
      oscillatory activity in the brain. SIGNIFICANCE: These results provide novel
      insights into the pattern of spatiotemporal dynamics underlying freezing of gait
      and may provide a potential means for therapeutic prediction and alleviation of
      freezing episodes in susceptible patients.

PMID- 24099921
TI  - Migrainous aura during carotid artery clamping: an ictal EEG study.

PMID- 24099922
TI  - Heterogeneity of root and nerve ultrasound pattern in CIDP patients.
AB  - OBJECTIVE: The few published ultrasound (US) studies on chronic inflammatory
      demyelinating polyradiculoneuropathy (CIDP) report diffusely increased cross
      sectional area (CSA) of nerves. The data are, however, heterogeneous and
      correlations with clinical history or disease severity are lacking. METHODS:
      Thirty-four patients with CIDP underwent US nerve evaluation by two neurologists
      blinded to clinical data. US nerve pattern for each patient was defined by a
      third neurologist blinded to clinical data. Three US classes were identified
      based on CSA and echogenicity: large nerves with hypoechoic nerves/fascicles
      (class 1); large nerves with heterogeneous hypo- and hyperechoic fascicles (class
      2); normal size nerve but abnormal hyperechoic array (class 3). RESULTS: In all
      patients, US nerve changes were observed: in most of the cases, enlarged nerves
      or nerve segments were observed. The three 'classes' of US nerve changes
      significantly correlated (R: 0.68, p<0.001) with disease duration, but not with
      age or Inflammatory Neuropathy Cause and Treatment (INCAT) disability score.
      CONCLUSIONS: US may be of adjunctive diagnostic value in CIDP assessment. Nerve
      morphological changes may mirror the underlying pathophysiological mechanisms and
      seem to correlate with disease duration. SIGNIFICANCE: These results offer the
      possibility of exploring the use of US to assess CIDP disease activity and
      treatment.

PMID- 24099923
TI  - What's hot in the anaerobe literature? Bacteroides and other non-clostridial
      anaerobes.
AB  - The vast microbiota in the human body is dominated by anaerobic gram-negative
      rods. The five recent publications reviewed here demonstrate important roles for
      Bacteroides species and other anaerobic bacteria both in the production of
      illness and the maintenance of health. 

PMID- 24099924
TI  - Taphonomic and paleoecological change in the large mammal sequence from Boomplaas
      Cave, western Cape, South Africa.
AB  - Excavations conducted by H.J. Deacon in the 1970s at Boomplaas Cave (BPA)
      uncovered a stratified sequence of Middle Stone Age (MSA) and Later Stone Age
      (LSA) deposits spanning the last >65,000 years. This study provides the first
      comprehensive and integrated taphonomic and paleoecological analysis of the BPA
      large mammals, with a focus on its implications for understanding human
      adaptations and environmental changes in southern Africa's Cape Floristic Region
      (CFR), an area that features prominently in understanding modern human origins.
      Taphonomic data indicate a complex history of human, carnivore, and raptor
      accumulation of the large mammal assemblage. The anthropogenic signal is largely
      absent from the bottom of the sequence (>65,000 years ago), intermediate in MSA
      and LSA assemblages from ~50,000 to 20,000 years ago, and strong in LSA deposits
      post-dating the Last Glacial Maximum (LGM). When viewed in the broader CFR
      context, the inferred occupation history of BPA is consistent with the hypothesis
      that both MSA and LSA human populations were concentrated on the submerged
      coastline from ~60,000 to ~20,000 years ago. Intensive occupation following the
      LGM parallels an apparent increase in regional population densities, which may
      have been driven in part by rising sea levels. The BPA ungulate assemblage is
      characterized by the rise and decline of a taxonomically diverse grazing
      community, which peaks during the LGM. These changes are not correlated with
      taphonomic shifts, meaning that they are likely driven by environmental factors,
      namely the expansion and contraction of grassland habitats. Changes in ungulate
      diversity indicate that effective precipitation was highest during the LGM,
      corresponding with an intensified winter rainfall system. This is consistent with
      recent arguments that the LGM in this region may not have been extremely harsh
      and arid.

PMID- 24099925
TI  - Environmental factors unveil dormant developmental capacities in multipotent
      progenitors of the trunk neural crest.
AB  - The neural crest (NC), an ectoderm-derived structure of the vertebrate embryo,
      gives rise to the melanocytes, most of the peripheral nervous system and the
      craniofacial mesenchymal tissues (i.e., connective, bone, cartilage and fat
      cells). In the trunk of Amniotes, no mesenchymal tissues are derived from the NC.
      In certain in vitro conditions however, avian and murine trunk NC cells (TNCCs)
      displayed a limited mesenchymal differentiation capacity. Whether this capacity
      originates from committed precursors or from multipotent TNCCs was unknown. Here,
      we further investigated the potential of TNCCs to develop into mesenchymal cell
      types in vitro. We found that, in fact, quail TNCCs exhibit a high ability to
      differentiate into myofibroblasts, chondrocytes, lipid-laden adipocytes and
      mineralizing osteoblasts. In single cell cultures, both mesenchymal and neural
      cell types coexisted in TNCC clonal progeny: 78% of single cells yielded
      osteoblasts together with glial cells and neurons; moreover, TNCCs generated
      heterogenous clones with adipocytes, myofibroblasts, melanocytes and/or glial
      cells. Therefore, alike cephalic NCCs, early migratory TNCCs comprised
      multipotent progenitors able to generate both mesenchymal and melanocytic/neural
      derivatives, suggesting a continuum in NC developmental potentials along the
      neural axis. The skeletogenic capacity of the TNC, which was present in the
      exoskeletal armor of the extinct basal forms of Vertebrates and which persisted
      in the distal fin rays of extant teleost fish, thus did not totally disappear
      during vertebrate evolution. Mesenchymal potentials of the TNC, although not
      fulfilled during development, are still present in a dormant state in Amniotes
      and can be disclosed in in vitro culture. Whether these potentials are not
      expressed in vivo due to the presence of inhibitory cues or to the lack of
      permissive factors in the trunk environment remains to be understood.

PMID- 24099926
TI  - Transcriptional regulation of tissue organization and cell morphogenesis: the fly
      retina as a case study.
AB  - Understanding how a functional organ can be produced from a small group of cells
      remains an outstanding question in cell and developmental biology. The developing
      compound eye of Drosophila has long been a model of choice for addressing this
      question by dissecting the cellular, genetic and molecular pathways that govern
      cell specification, differentiation, and multicellular patterning during
      organogenesis. In this review, the author focussed on cell and tissue
      morphogenesis during fly retinal development, including the regulated changes in
      cell shape and cell packing that ultimately determine the shape and architecture
      of the compound eye. In particular, the author reviewed recent studies that
      highlight the prominent roles of transcriptional and hormonal controls that
      orchestrate the cell shape changes, cell-cell junction remodeling and polarized
      membrane growth that underlie photoreceptor morphogenesis and retinal patterning.

PMID- 24099927
TI  - [Delayed onset holocarboxylase synthetase deficiency with normal pyruvate
      carboxylase activity].
AB  - We report a case of holocarboxylase synthetase deficiency with normal pyruvate
      carboxylase activity in the lymphocytes of an 8 year-old girl with clinical
      toxicity without the classic dermatological involvement. The identification of
      three nucleotide changes in the holocarboxylase synthetase (HLCS) gene, only one
      of them described as a pathogenic mutation could be related to a slight variant
      of the disease that would explain the unusual presentation beyond the age of
      infant. Treatment with biotin at 40 mg/day with protein controlled diet allows
      normal physical growth and psychomotor development for their age.

PMID- 24099929
TI  - [Incidence of unplanned extubations in a neonatal intensive care unit. A before
      and after study].
AB  - INTRODUCTION: Unplanned extubations (UE) of mechanically ventilated newborns
      involves an undesirable increase in morbidity and mortality. OBJECTIVE: A 2-stage
      study compared the frequency of UE in a Neonatal Intensive Care Unit before and
      after the implementation of a program of preventive measures to decrease UE.
      PATIENTS AND METHODS: A before and after prospective study included all
      mechanically ventilated newborns participating in the 2 stage study from May
      December 2011 and June-December 2012. In stage 1, the rate of UE per 100
      intubated patient days was calculated and the characteristics of unplanned
      extubated newborns, circumstances of UE occurrence and need for re-intubation
      were studied. Consequently, a program of preventive measures for UE was designed
      and implemented, with the same variables being analysed in stage 2. RESULTS: No
      differences were found in patient characteristics during the two stages. Stage 1,
      incidence of UE was 5/100 intubated patient days; Stage 2, 4.5 UE/100 intubated
      patient days (P=.657). In both stages, most UE occurred during patient handling
      with re-intubation incidence at 77.4% and 67.7%, respectively. The combined rate
      of both stages during summer months of July, August and September was 6.2 UE/100
      intubation days, in contrast with the remaining months of both stages: UE
      incidence rate, 3.4 UE/100 intubation days (p=.043). CONCLUSIONS: The
      implementation of a preventive measures program did not significantly reduce the
      incidence of UE. The summer period showed the highest incidence of UE.

PMID- 24099928
TI  - [Influence of gestational age, type of delivery, and resuscitation, on the
      incidence of pneumothorax in term neonates].
AB  - BACKGROUND: Elective caesarean section before 39 weeks gestational age (GA) has
      been associated with a higher incidence of iatrogenic respiratory distress and
      pneumothorax in term newborn babies, probably because of a higher respiratory
      morbidity and the need for resuscitation. These factors have not been
      systematically evaluated in our patients. OBJECTIVE: To determine whether the
      gestational age, type of delivery, and intensity of resuscitation, are associated
      with an increase in the incidence of pneumothorax in term neonates. PATIENTS AND
      METHODS: Full term neonates (>= 37 weeks GA) born in our maternity unit from
      January 2006 to December 2010 were studied, along with the type of delivery
      (vaginal, forceps or caesarean section). Advanced cardiopulmonary resuscitation
      (CPR) was defined as the need of bag and mask intermittent ventilation,
      intubation, chest compression, and/or administration of medication. The diagnosis
      of pneumothorax was clinical and radiological in all cases. RESULTS: A total of
      32,238 full term newborns were included. Type of delivery: vaginal 76.1%, C
      section 12.4%, and forceps 11.5%. The incidence of pneumothorax was 0.316%. It
      was significantly higher in C-section (0.85%), than in forceps (0.59%), or non
      instrumental vaginal deliveries (0.19%) (P<.001), and in infants >= 40 weeks GA
      (0.37%) compared to <= 39 weeks GA (0.24%) (P=.033), and in advanced CPR (4.29%)
      compared to basic CPR (0.18%) (P<.001). CONCLUSIONS: A GA >= 40 weeks, C-section,
      or forceps delivery, and advanced CPR immediately after birth were significantly
      associated with a higher incidence of pneumothorax in full term newborn babies.
      In our population, we did not observe an increase in pneumothorax among neonates
      born by elective C-section before 39 weeks of gestation.

PMID- 24099930
TI  - Astrocyte domains and the three-dimensional and seamless expression of
      consciousness and explicit memories.
AB  - The expression of consciousness and the site of memory storage within the brain
      are unknown despite over a century of intense empirical scrutiny. Recent
      anatomical studies show that human protoplasmic astrocytes form innumerable
      uniform polyhedral tessellating domains that are arranged three-dimensionally.
      This complex geometric structure provides a matrix for seamless and three
      dimensional expression of consciousness and explicit memories. These studies, in
      conjunction with physiological data, demonstrate how this may be achieved: 1.
      Individual protoplasmic astrocytes occupy separate three-dimensional non
      overlapping (i.e., tessellating) territories known as domains. Thus, billions of
      contiguous and continuous domains tile mammalian cortical gray matter. 2. Each
      domain subtends approximately 90,000 rodent and 2,000,000 human tripartite
      synapses that signal to perisynaptic astrocyte processes which encode and
      integrate synaptic information. Neuron to astrocyte signalling is as rapid as
      neuron to neuron signaling. 3. Astrocytes are exquisitely sensitive to neural
      activity and distinguish synapse from numerous afferent pathways with different
      neurotransmitters or neuromodulators. Therefore, synaptic information is
      dynamically integrated within a global matrix of tessellating astrocyte domains.
      4. Astrocytes of the sensory cortex respond to peripheral stimulation in vivo,
      and some have the ability to distinguish sensory input in more refined detail
      than surrounding neurons (e.g., visual cortex). Additionally, astrocytes of the
      cortex and cerebellum react in concert with activity of awake and behaving
      animals. 5. Domains are extensively interconnected by gap junctions that transmit
      molecules, many important for information processing and transcription, through
      complex syncytial networks. This adds an additional level of complexity to
      interactions between astrocyte domains that may extend over large areas including
      the entire neocortex. HYPOTHESIS: Consciousness is seamlessly expressed in a
      three-dimensional matrix consisting of billions of tessellating cortical
      astrocyte domains that bind attended sensory information. The temporal sequence
      (stream of consciousness) depends on the global distribution of sequential neural
      activity. The matrix may also be utilized to encode and store explicit memories.

PMID- 24099931
TI  - Breastfeeding as a possible deterrent to autism--a clinical perspective.
AB  - The emergence of autism in young children appears to result from dysmyelination
      of brain neurons, related to inadequate supply of insulin-like growth factor
      (IGF) in the newborn. This report is intended to bring together relevant
      observations from prior research to develop a new, innovative hypothesis to
      elucidate the mechanism underlying autism development. The deficiency of IGF in
      affected infants may be due to a combination of genetic and environmental factors
      yet to be determined. If this hypothesis is correct, breastfeeding in particular
      could increase IGF levels, thereby compensating for an inborn deficiency of the
      growth factor. 

PMID- 24099932
TI  - Partial volume effect estimation and correction in the aortic vascular wall in
      PET imaging.
AB  - We evaluated the impact of partial volume effect (PVE) in the assessment of
      arterial diseases with (18)FDG PET. An anthropomorphic digital phantom enabling
      the modeling of aorta related diseases like atherosclerosis and arteritis was
      used. Based on this phantom, we performed GATE Monte Carlo simulations to produce
      realistic PET images with a known organ segmentation and ground truth activity
      values. Images corresponding to 15 different activity-concentration ratios
      between the aortic wall and the blood and to 7 different wall thicknesses were
      generated. Using the PET images, we compared the theoretical wall-to-blood
      activity-concentration ratios (WBRs) with the measured WBRs obtained with five
      measurement methods: (1) measurement made by a physician (Expert), (2) automated
      measurement supposed to mimic the physician measurements (Max), (3) simple
      correction based on a recovery coefficient (Max-RC), (4) measurement based on an
      ideal VOI segmentation (Mean-VOI) and (5) measurement corrected for PVE using an
      ideal geometric transfer matrix (GTM) method. We found that Mean-VOI WBRs values
      were strongly affected by PVE. WBRs obtained by the physician measurement, by the
      Max method and by the Max-RC method were more accurate than WBRs obtained with
      the Mean-VOI approach. However Expert, Max and Max-RC WBRs strongly depended on
      the wall thickness. Only the GTM corrected WBRs did not depend on the wall
      thickness. Using the GTM method, we obtained more reproducible ratio values that
      could be compared across wall thickness. Yet, the feasibility of the
      implementation of a GTM-like method on real data remains to be studied. 

PMID- 24099933
TI  - Effects of ascorbic acid and sugars on solubility, thermal, and mechanical
      properties of egg white protein gels.
AB  - The effects of reducing sugars (fructose, glucose, ribose, and arabinose),
      sucrose, and ascorbic acid were studied on thermo-mechanical properties and
      crosslinking of egg white proteins (EWP) through Maillard reaction. Sugars (0%,
      1%, 5%, and 10%) and ascorbic acid (0%, 0.25%, 0.5%, and 2.5%) were added to EWP
      solutions. Thermal denaturation and crosslinking of EWP were characterized by
      differential scanning calorimetry (DSC). Mechanical properties (failure strength,
      failure strain and Young's modulus) of modified and unmodified EWP gels were
      evaluated by texture analyzer. Ascorbic acid decreased thermal denaturation
      temperature of EWP, but the reducing sugars increased the denaturation
      temperature. DSC thermograms of EWP showed that ascorbic acid exhibited an
      exothermic transition (~110  degrees C) which was attributed to Maillard
      crosslinking of the protein. The reduction in pH (from 7.21 to ~6) and protein
      solubility of egg white protein gel (from ~70% to ~10%) provides further evidence
      of the formation of Maillard cross-linking. Reactive sugars (ribose and
      arabinose) increased the mechanical properties of EWP gels, whereas ascorbic acid
      decreased the mechanical properties. Generally, the effect of ascorbic acid was
      more pronounced than that of various reducing sugars on the thermal and
      mechanical properties of egg white proteins.

PMID- 24099934
TI  - Synthesis and in vitro cellular evaluation of novel anti-tumor norcantharidin
      conjugated chitosan derivatives.
AB  - Norcantharidin-conjugated chitosan conjugates (NCTD-CSs) with different degrees
      of substitution (DS, 60.2% and 97.9%) were synthesized and characterized by (1)H
      NMR, FT-IR, and XRD. In comparison with CS, the NCTD-CSs had lower crystallinity
      and better water solubility. Less than 6% NCTD was released from the NCTD-CSs
      through the hydrolysis of ester bonds in phosphate-buffered solution (PBS, pH 5.0
      and 7.4) within 16 days, showing sustained drug release characteristic. The
      result of cytoxicity study showed that the NCTD-CSs were cytotoxic to MGC80-3
      cells and their cytotoxicity was lower than that of NCTD. Fluorescence microscope
      and flow cytometry analysis demonstrated that the amount of the NCTD-CSs uptaken
      by MGC80-3 cells increased as incubation time. Confocal microscopy study showed
      that the NCTD-CSs were internalized into cells by endocytosis and mainly
      localized in lysosomes within 24h. It was found that the NCTD-CSs arrested MGC80
      3 cell cycle at G2/M phase and induced cell death via cell apoptosis similarly to
      NCTD. These results indicated that the NCTD-CSs might be an efficient NCTD
      delivery system for cancer therapy.

PMID- 24099935
TI  - Preparation and characterization of poly(L-lactide)-co-poly(trimethylene
      carbonate)/talc film.
AB  - Poly(L-lactide)-co-poly(trimethylene carbonate) (PLLA-PTMC) composites with
      various talc content as food packaging materials were prepared by solvent casting
      method. The effect of talc filler loading (0, 1, 2, and 3 wt%) on phase
      morphology of PLLA-PTMC/Talc composites and improvement in resulting properties
      were reported. The X-ray diffraction (XRD) patterns and differential scanning
      calorimetry (DSC) curves indicated that the crystallinity of PLLA-PTMC/Talc
      composites increased. Fourier transform infrared spectroscopy (FTIR) suggested
      that there were strong interactions between PLLA-PTMC copolymer and talc filler.
      The scanning electron microscopy (SEM) image of composite films revealed certain
      homogeneity between PLLA-PTMC and Talc, when the talc filler did not exceed 3
      wt%. The elongation at break of composite films significantly (p<0.05) improved
      with the addition of talc filler. Furthermore, there were 23%, 31%, and 14%
      improvement in water vapor barrier properties at 1, 2, and 3 wt% of talc in PLLA
      PTMC/Talc composites, respectively. This had been confirmed by thermogravimetric
      analysis (TGA).

PMID- 24099936
TI  - Microemulsion can improve the immune-enhancing activity of propolis flavonoid on
      immunosuppression and immune response.
AB  - The objective of the present study was to investigate whether the immune
      enhancing activity of propolis flavone (PF) could be improved after PF was made
      into PF microemulsion (PFM). Two experiments were carried out. In
      immunosuppression experiment, the immune-enhancing effect of PFM in
      immunosuppressive chickens was performed. The results showed that PFM at high and
      medium doses was able to overcome the CTX-induced immunosuppression,
      significantly increases the immune organ indexes, enhances lymphocyte
      proliferation and improves the concentrations of IL-2 and IL-6 in serum when
      compared with PF. In immune response experiment, the adjuvant effect of PFM at
      three doses and PF were compared on chickens which were immunized intramuscularly
      with Avian Influenza Recombinant Newcastle Disease Virus bivalent Vaccine. The
      results showed that PFM at high and medium doses could significantly promote
      lymphocyte proliferation, enhances antibody titer and the concentrations of IgG
      and IgM, and its efficacy were significantly better than PF at most time points.
      These results indicated that PFM could significantly improve the immune-enhancing
      activity and adjuvanticity of PF, and its high and medium doses possessed the
      best efficacy. Therefore, the microemulsion could be used as an effective
      formulation for enhancing the bioavailability of PF. 

PMID- 24099937
TI  - Optimization of recombinant hexaoligochitin-producing chitinase production with
      response surface methodology.
AB  - Hexaoligochitin produced by chitinase, ASCHI61, from Aeromonas schubertii was
      recently expressed. In this work, the optimal conditions for the mass production
      of ASCHI61 were investigated. The efficiency of recombinant protein expression in
      Escherichia coli was determined by various parameters, including the pH of the
      culture medium, induction temperature, shaking speed, inducer concentration, and
      induction period. The optimization experiments could be simplified through a
      statistical design of experiments (response surface methodology). From the
      fractional factorial design, the interactive effect of induction temperature and
      time was the most significant. The total activity of the enzyme was 32,092 U at
      23.9  degrees C with 115 min of induction. Under those conditions, the total
      activity of the recombinant protein was 30,650 U in the fermentation experiments,
      with an error of only 4.8%. The total activity of ASCHI61 increased 1.54-fold
      under the optimal conditions. Based on the results, ASCHI61 can be expressed more
      for hexaoligochitin production.

PMID- 24099938
TI  - Topical gels of lidocaine HCl using cashew gum and Carbopol 940: preparation and
      in vitro skin permeation.
AB  - The present study was attempted to prepare novel topical gels of 4% lidocaine HCl
      using cashew gum and Carbopol 940. The prepared gels were evaluated for pH,
      viscosity, and in vitro skin permeation through excised porcine skin. The pH of
      these topical gels was found within the range of 5.98-6.06; whereas, the
      viscosity was found 4.58 * 10(6) to 4.88 * 10(6) cps. The in vitro skin
      permeation from these gels showed permeation flux range, 851.34 +/- 9.16 to
      1568.15 +/- 14.03 MUg/cm(2)/h. The highest permeation flux (1568.15 +/- 14.03
      MUg/cm(2)/h) was observed, when 0.01% menthol was added, which was higher than
      that of the marketed 4% lidicaine HCl topical gel (1355.41 +/- 10.92
      MUg/cm(2)/h). These topical gels found best-fit with Korsmeyer-Peppas model and
      almost the super case-II transport mechanism. The stability study revealed that
      these gels were physically stable without occurrence of syneresis.

PMID- 24099939
TI  - Study on structure and thermal stability properties of lignin during
      thermostabilization and carbonization.
AB  - Soda lignin was first thermostabilized prior to carbonization. The composition,
      structures and thermal properties of treated lignin were investigated by EA, TGA
      MS, (13)C NMR, TGA, and Raman. EA and TGA-MS results showed that the hydrogen
      content decreased continuously and the oxygen content increased up to 260 
      degrees C then decreased and the carbon content increased passively during
      thermostabilization. (13)C NMR results revealed that thermostabilization could be
      divided into three stages according to the evolution of the oxygenated structures
      content: <260  degrees C, 260-290  degrees C, >290  degrees C. Raman analysis
      showed that R values at each carbonization temperature were concave-down and non
      symmetrical parabolic type and the 260  degrees C thermostabilized lignin after
      1400  degrees C carbonized obtained the minimum R value 1.84. TGA results
      indicated that overall yields reflecting thermal stability of the
      thermostabilized samples, especially thermostabilized at 260-290  degrees C, were
      higher than that of untreated lignin.

PMID- 24099940
TI  - Preparation and characterization of pH-responsive guar gum microspheres.
AB  - Guar gum, being the natural polymer is renewable, nontoxic, biocompatible and
      biodegradable. Therefore, it is the perfect material to formulate particulates or
      microspheres for potential applications in pharmaceutical. The formulation of
      material in nano/microsphere scale offers new rich in application potential. In
      view of that, novel biodegradable and pH-sensitive hydrogels composed of pH
      sensitive methacrylic acid (MAc) and a biodegradable guar gum were synthesized by
      grafting reactions. Water-in-oil (w/o) emulsion method was used to direct the pH
      sensitive material in microspheres shape using bi-functional glutaraldehyde (GA)
      as crosslinker. The synthesized microspheres were characterized by FTIR and SEM
      (different magnification). The swelling ratios of hydrogels in buffer solutions
      showed a pH-dependent profile at physiological pH. In vitro release data was
      analyzed using Fick's law, which indicated swelling controlled super case II
      transport of BSA through the synthesized microspheres. Therefore, in conclusion,
      as ascertained from the results the introduction of -COOH moieties along the guar
      gum chain drastically increases the end-use performance due to pH-sensitivity.

PMID- 24099941
TI  - Reversible and competitive inhibitory kinetics of amoxicillin on mushroom
      tyrosinase.
AB  - In the present work, we investigated the inhibitory effects of amoxicillin, a
      bacteriolytic beta-lactam antibiotic drug, on the rate of monophenol
      hydroxylation and o-diphenol oxidation catalyzed by mushroom tyrosinase. The
      results showed that amoxicillin could inhibit both monophenolase and diphenolase
      activities. For monophenolase activity, the inhibition on reaction rate was dose
      dependent, while the influence on lag period was not obvious. For diphenolase
      activity, amoxicillin was found to be a reversible inhibitor, with an IC50 value
      of 9.0 +/- 1.8 mM. Kinetics analysis showed that amoxicillin was a mixed type
      inhibitor of the enzyme with KI and KIS values of 8.30 mM and 44.79 mM,
      respectively. Further, the molecular mechanism underlying the inhibition of
      tyrosinse by amoxicillin was investigated by means of fluorescence quenching and
      molecular docking techniques. The results showed that amoxicillin could form
      static interaction with the catalytic pocket of the enzyme through the
      interaction of amoxicillin with the dicopper irons and amino acid residues in the
      enzyme active center. Our results contributed to the usage of amoxicillin as a
      potential tyrosinase inhibitor in the field of medicinal industry and could also
      provide guidance in the design of novel tyrosinase inhibitors.

PMID- 24099942
TI  - Effect of preparation parameters on ultra low molecular weight
      chitosan/hyaluronic acid nanoparticles.
AB  - Nanoparticles of ultra low molecular weight chitosan (ULMWCS)/hyaluronic acid
      (HA) were prepared by ion gelation. Three independent variables, namely, ratio of
      concentration of ULMWCS to HA (CS/HA), pH of solution and stirring time were
      studied to identify their effects on size, polydispersity and zeta potential of
      prepared nanoparticles using a Box-Behnken design. Results showed that pH and
      CS/HA have a direct effect on size, while increase of stirring time decreases the
      size of nanoparticles. Additionally, it was shown that all the independent
      parameters have direct effects on zeta potential. Also, the minimum
      polydispersity index was observed at lowest values of CS/HA. The model also
      predicted that the optimum values are 4.15, 4.14 and 180 (min) for the CS/HA,
      solution pH and stirring time, respectively. The obtained preparation had a size
      of 200 nm, polydispersity index of 0.37, and zeta potential of 13.0 mV.

PMID- 24099943
TI  - Purification, characterization and biological activities in vitro of
      polysaccharides extracted from tea seeds.
AB  - Three polysaccharide fractions (NTSPS, ATSPS1-1 and ATSPS2) were isolated and
      purified from the water extract of tea (Camellia sinensis) seeds with yields of
      32.74%, 25.22%, and 11.09%, respectively. The average molecular weight of NTSPS,
      ATSPS1-1 and ATSPS2 was determined by HPGPC system, with an Mw of 4.588, 500 and
      100 kDa, respectively. Monosaccharide analysis by ion chromatography revealed
      they differed from each other in monosaccharide kinds and molar ratio.
      Furthermore, ATSPS1-1 and ATSPS2 were heteropolysaccharide bounded with protein
      (2.83% and 2.12%) and 17 general amino acids were detected in them on an ion
      chromatographic analyzer. The IR spectrum of ATSPS1-1 and ATSPS2 revealed the
      typical characteristics of polysaccharides and protein. In addition, the
      antitumor and immunological activity of the three polysaccharide fractions in
      vitro were also evaluated. It was found inhibition activity of NTSPS, ATSPS1-1
      and ATSPS2 on K562 cells increased with increasing sample concentration and the
      inhibition ratios of them at 400 MUg/mL were beyond 30.13 +/- 3.54%, 36.61 +/-
      2.75% and 32.33 +/- 2.53%, respectively. They also exhibited strong ability in
      promoting proliferation of mice splenic lymphocyte. Results of these studies
      indicated the three purified polysaccharides had a potential application as
      natural antitumor drugs.

PMID- 24099946
TI  - Understanding the service use patterns of emergency department frequent
      attenders: could paediatric outreach be a solution?

PMID- 24099944
TI  - Offline analysis of context contribution to ERP-based typing BCI performance.
AB  - OBJECTIVE: We aim to increase the symbol rate of electroencephalography (EEG)
      based brain-computer interface (BCI) typing systems by utilizing context
      information. APPROACH: Event related potentials (ERP) corresponding to a stimulus
      in EEG can be used to detect the intended target of a person for BCI. This
      paradigm is widely utilized to build letter-by-letter BCI typing systems.
      Nevertheless currently available BCI typing systems still require improvement due
      to low typing speeds. This is mainly due to the reliance on multiple repetitions
      before making a decision to achieve higher typing accuracy. Another possible
      approach to increase the speed of typing while not significantly reducing the
      accuracy of typing is to use additional context information. In this paper, we
      study the effect of using a language model (LM) as additional evidence for intent
      detection. Bayesian fusion of an n-gram symbol model with EEG features is
      proposed, and a specifically regularized discriminant analysis ERP discriminant
      is used to obtain EEG-based features. The target detection accuracies are
      rigorously evaluated for varying LM orders, as well as the number of ERP-inducing
      repetitions. MAIN RESULTS: The results demonstrate that the LMs contribute
      significantly to letter classification accuracy. For instance, we find that a
      single-trial ERP detection supported by a 4-gram LM may achieve the same
      performance as using 3-trial ERP classification for the non-initial letters of
      words. SIGNIFICANCE: Overall, the fusion of evidence from EEG and LMs yields a
      significant opportunity to increase the symbol rate of a BCI typing system.

PMID- 24099947
TI  - Preventing hyponatraemic dehydration in cystic fibrosis: a cautionary note to
      take coconut water with a pinch of salt.

PMID- 24099948
TI  - The role of mode of delivery on elastic fiber architecture and vaginal vault
      elasticity: a rodent model study.
AB  - We report on an experimental study of the role of mode of delivery and pregnancy
      on the architecture of vaginal elastic fibers and vaginal vault elasticity in
      female Sprague-Dawley rats. In primiparous rats submitted to spontaneous or
      Cesarean delivery and virgin rats submitted to simulated delivery, the tortuosity
      of elastic fibers (defined as the ratio of length to end-to-end distance) was
      observed to decrease when measured from two days to two weeks postpartum. In
      addition, the measured tortuosity of elastic fibers in multiparous rats was
      greater than that of virgin rats. The tortuosity of elastic fibers of all rats
      measured at two days postpartum was found to be similar to that of multiparous
      rats. At two weeks postpartum the measured tortuosity of vaginal elastic fibers
      was indistinguishable from virgin rats, regardless of the delivery method.
      Borrowing from the field of polymer physics, a model is suggested that connects
      elastic fiber tortuosity to the resulting tension under an applied stress; fibers
      having high tortuosity are expected to provide less structural support than more
      linear, low tortuosity fibers. To probe the macroscopic effects in elasticity due
      to architectural changes observed in elastic fibers, we have measured the
      stiffness of the vaginal vault in each cohort using a pressure-infusion system.
      The vaginal vault stiffness of all primiparous rats measured two weeks postpartum
      was greater than that measured two days postpartum. In addition, the vaginal
      vault of virgin rats was stiffer than that of multiparous rats. These
      observations confirmed that vaginal vault elastic fibers undergo significant
      remodeling due to pregnancy and parturition, and that the complex remodeling may
      be a significant contributor to tissue elasticity. Remarkably, regardless of the
      mode of delivery or simulated tissue trauma, elastic fiber tortuosity is observed
      to decrease from two days to two weeks postpartum indicating the onset of repair
      and recovery of tissue stiffness. 

PMID- 24099950
TI  - Measurement of viscoelastic properties in multiple anatomical regions of acute
      rat brain tissue slices.
AB  - Mechanical property data for brain tissue are needed to understand the
      biomechanics of neurological disorders and response of the brain to different
      mechanical and surgical forces. Most studies have characterized mechanical
      behavior of brain tissues over large regions or classified tissue properties for
      either gray or white matter regions only. In this study, spatially heterogeneous
      viscoelastic properties of ex vivo rat brain tissue slices were measured in
      different anatomical regions including the cerebral cortex, caudate/putamen, and
      hippocampus using an optical coherence tomography (OCT) indentation system. Cell
      viability was also tested to observe neuronal degeneration and morphological
      changes in tissue slices and provide a proper timeline for mechanical tests.
      Shear modulus was estimated by fitting normalized deformation data (D/ti), which
      was defined as the ratio of deformation depth (D) to initial thickness of the
      tissue slice (ti), to a viscoelastic finite element model. The estimated shear
      modulus decayed nonlinearly over 10min in each anatomical region, and the range
      of instantaneous to equilibrium shear modulus was 3.8-0.54kPa in the cerebral
      cortex, 1.4-0.27kPa in the hippocampus and 1.0-0.17kPa in the caudate/putamen.
      Although these regions are all gray matter structures, their measured mechanical
      properties were significantly different. Accurate measurement of inter-regional
      variations in mechanical properties will contribute to improved understanding
      organ-level structural parameters and regional differential susceptibility to
      deformation injury within CNS tissues. 

PMID- 24099949
TI  - Tribolayer formation in a metal-on-metal (MoM) hip joint: an electrochemical
      investigation.
AB  - The demand for total hip replacement (THR) surgery is increasing in the younger
      population due to faster rehabilitation and more complete restoration of
      function. Up to 2009, metal-on-metal (MoM) hip joint bearings were a popular
      choice due to their design flexibility, post-operative stability and relatively
      low wear rates. The main wear mechanisms that occur along the bearing surface of
      MoM joints are tribochemical reactions that deposit a mixture of wear debris,
      metal ions and organic matrix of decomposed proteins known as a tribolayer. No in
      depth electrochemical studies have been reported on the structure and
      characteristics of this tribolayer or about the parameters involved in its
      formation. In this study, we conducted an electrochemical investigation of
      different surfaces (bulk-like: control, nano-crystalline: new implant and
      tribolayer surface: retrieved implant) made out of two commonly used hip CoCrMo
      alloys (high-carbon and low-carbon). As per ASTM standard, cyclic polarization
      tests and electrochemical impedance spectroscopy tests were conducted. The
      results obtained from electrochemical parameters for different surfaces clearly
      indicated a reduction in corrosion for the tribolayer surface (Icorr:
      0.76MUA/cm(2)). Further, polarization resistance (Rp:2.39+/-0.60MOmega/cm(2)) and
      capacitance (Cdl:15.20+/-0.75MUF/cm(2)) indicated variation in corrosion kinetics
      for the tribolayer surface, that attributed to its structure and stability in a
      simulated body environment. 

PMID- 24099951
TI  - Antibody-dependent enhancement of PRRSV infection down-modulates TNF-alpha and
      IFN-beta transcription in macrophages.
AB  - Porcine reproductive and respiratory syndrome (PRRS) is an infectious disease,
      resulting in important economic losses in pig farming. Previous studies have
      shown that Fcgamma receptor (FcgammaR)-mediated entry of infectious PRRSV immune
      complexes into macrophages plays a pivotal role in the pathogenesis of the
      disease. This study demonstrates that PRRSV was able to suppress the
      transcription of key antiviral genes tumor necrosis factor-alpha (TNF-alpha) and
      interferon-beta (IFN-beta), when infection was via the ADE pathway. Investigation
      of this infection pathway found that PRRSV suppresses the antiviral genes by
      disrupting the transcription of the genes coding for the associated transcription
      factors interferon regulatory factor-1 (IRF-1), interferon regulatory factor-3
      (IRF-3) and nuclear factor kappa B (NF-kappaB). The ADE pathway of infection
      allows PRRSV to specifically target antiviral genes and alters the innate
      intracellular immune responses in macrophages. The ADE mechanism described in
      this study furthers our understanding of pathogenesis following PRRSV infection
      and is of general relevance to virally induced disease and in relation to
      antiviral vaccination strategies. 

PMID- 24099952
TI  - Response to letter to the editor.

PMID- 24099953
TI  - Visceral sensitivity correlates with decreased regional gray matter volume in
      healthy volunteers: a voxel-based morphometry study.
AB  - Regional changes in brain structure have been reported in patients with altered
      visceral sensitivity and chronic abdominal pain, such as in irritable bowel
      syndrome. It remains unknown whether structural brain changes are associated with
      visceral sensitivity. Therefore, we present the first study in healthy
      individuals to address whether interindividual variations in gray matter volume
      (GMV) in pain-relevant regions correlate with visceral sensitivity. In 92 healthy
      young adults (52 female), we assessed rectal sensory and pain thresholds and
      performed voxel-based morphometry (VBM) to compute linear regression models with
      visceral sensory and pain thresholds, respectively, as independent variable and
      GMV in a priori-defined regions of interest (ROIs) as dependent variable. All
      results were familywise error (FWE) corrected at a level of PFWE<.05 and covaried
      for age. The mean (+/-SEM) rectal thresholds were 14.78+/-0.46mm Hg for first
      sensation and 33.97+/-1.13mm Hg for pain, without evidence of sex differences.
      Lower rectal sensory threshold (ie, increased sensitivity) correlated
      significantly with reduced GMV in the thalamus, insula, posterior cingulate
      cortex, ventrolateral and orbitofrontal prefrontal cortices, amygdala, and basal
      ganglia (all PFWE<.05). Lower rectal pain threshold was associated with reduced
      GMV in the right thalamus (PFWE=.051). These are the first data supporting that
      increased visceral sensitivity correlates with decreased gray matter volume in
      pain-relevant brain regions. These findings support that alterations in brain
      morphology not only occur in clinical pain conditions but also occur according to
      normal interindividual variations in visceral sensitivity. 

PMID- 24099954
TI  - Psychological, surgical, and sociodemographic predictors of pain outcomes after
      breast cancer surgery: a population-based cohort study.
AB  - Chronic postsurgical pain (CPSP) is a common postoperative adverse event
      affecting up to half of women undergoing breast cancer surgery, yet few
      epidemiological studies have prospectively investigated the role of preoperative,
      intraoperative, and postoperative risk factors for pain onset and chronicity. We
      prospectively investigated preoperative sociodemographic and psychological
      factors, intraoperative clinical factors, and acute postoperative pain in a
      prospective cohort of 362 women undergoing surgery for primary breast cancer.
      Intraoperative nerve handling (division or preservation) of the
      intercostobrachial nerve was recorded. At 4 and 9months after surgery, incidence
      of chronic painful symptoms not present preoperatively was 68% and 63%,
      respectively. Univariate analysis revealed that multiple psychological factors
      and nerve division was associated with chronic pain at 4 and 9months. In a
      multivariate model, independent predictors of CPSP at 4months included younger
      age and acute postoperative pain (odds ratio [OR] 1.34, 95% confidence interval
      [CI] 1.12 to 1.60), whereas preoperative psychological robustness (OR 0.70, 95%
      CI 0.49 to 0.99), a composite variable comprising high dispositional optimism,
      high positive affect, and low emotional distress, was protective. At 9months,
      younger age, axillary node clearance (OR 2.97, 95% CI 1.09 to 8.06), and severity
      of acute postoperative pain (OR 1.17, 95% CI 1.00 to 1.37) were predictive of
      pain persistence. Of those with CPSP, 25% experienced moderate to severe pain and
      40% were positive on Douleur Neuropathique 4 and Self-Complete Leeds Assessment
      of Neuropathic Symptoms and Signs pain scales. Overall, a high proportion of
      women report painful symptoms, altered sensations, and numbness in the upper body
      within the first 9months after resectional breast surgery and cancer treatment. 

PMID- 24099955
TI  - Achlorophyllous alga Prototheca zopfii oxidizes n-alkanes with different carbon
      chain lengths through a unique subterminal oxidation pathway.
AB  - Some Prototheca spp. were previously reported to convert n-hexadecane to 5
      hexadecanol and then to 5-hexadecanone through a unique subterminal oxidation
      pathway. Further analysis of derivatives derived from n-hexadecane indicated that
      Prototheca zopfii oxidized n-alkanes with C11 to C17 chain lengths at not only
      the 5th but also the 4th, 3rd and 2nd positions.

PMID- 24099956
TI  - Method of phorbol ester degradation in Jatropha curcas L. seed cake using rice
      bran lipase.
AB  - A novel enzymatic degradation of phorbol esters (PE) in the jatropha seed cake
      was developed using lipase. Cihera rice bran lipase had the highest ability to
      hydrolyze PE, and reduced PE to a safe level after 8 h of incubation. Enzymatic
      degradation may be a promising method for PE degradation.

PMID- 24099957
TI  - Near-infrared spectroscopy monitoring of the collateral network prior to, during,
      and after thoracoabdominal aortic repair: a pilot study.
AB  - OBJECTIVE: The aim of this study was to evaluate the feasibility of non-invasive
      monitoring of the paraspinous collateral network (CN) oxygenation prior to,
      during, and after thoracoabdominal aortic repair in a clinical series. METHODS:
      Near-infrared spectroscopy optodes were positioned bilaterally-over the thoracic
      and lumbar paraspinous vasculature-to transcutaneously monitor muscle oxygenation
      of the CN in 20 patients (age: 66 +/- 10 years; men = 11) between September 2010
      and April 2012; 15 had open thoracoabdominal aortic repair (Crawford II and III),
      three had thoracic endovascular aortic repair (TEVAR; Crawford I), and two had a
      hybrid repair (Crawford II). CN oxygenation was continuously recorded until 48
      hours postoperatively. RESULTS: Hospital mortality was 5% (n = 1), 15% suffered
      ischemic spinal cord injury (SCI). Mean thoracic CN oxygenation saturation was
      75.5 +/- 8% prior to anesthesia (=baseline) without significant variations
      throughout the procedure (during non-pulsatile cooling on cardiopulmonary bypass
      and with aortic cross-clamping; range = 70.6-79.5%). Lumbar CN oxygenation (LbS)
      dropped significantly after proximal aortic cross-clamping to a minimum after
      11.7 +/- 4 minutes (74 +/- 13% of baseline), but fully recovered after
      restoration of pulsatile flow to 98.5% of baseline. During TEVAR, stent-graft
      deployment did not significantly affect LbS. Three patients developed relevant
      SCI (paraplegia n = 1/paraparesis n = 2). In these patients LbS reduction after
      aortic cross-clamping was significantly lower compared with patients who did not
      experience SCI (p = .041). CONCLUSIONS: Non-invasive monitoring of CN oxygenation
      prior to, during, and after thoracoabdominal aortic repair is feasible. Lumbar CN
      oxygenation levels directly respond to compromise of aortic blood circulation.

PMID- 24099958
TI  - Is cytomegalovirus testing of blood products still needed for hematopoietic stem
      cell transplant recipients in the era of universal leukoreduction?
AB  - Hematopoietic stem cell transplantation (HSCT) recipients are a high-risk,
      immunocompromised group of patients who receive frequent transfusions after
      transplantation. Transfusion of cytomegalovirus (CMV)-negative blood products has
      long been the standard of care to prevent transfusion-transmitted CMV in this
      patient population. Leukoreduction of blood products before transfusion has been
      shown to significantly reduce the risk of transfusion-transmitted CMV. In the era
      of universal leukoreduction in Canada, the need for CMV testing of blood products
      remains unclear. We sought to identify whether there is a difference in
      transfusion-transmitted CMV viremia in patients receiving only leukoreduced
      versus CMV-negative and leukoreduced blood products in HSCT recipients. Patients
      who were CMV negative and received an allogeneic HSCT from a CMV-negative donor
      between October 1, 1999 and June 30, 2012 were included in the analysis.
      Transfusion data were collected from The Ottawa Hospital Blood Bank and Canadian
      Blood Services. CMV viremia was defined as PCR positivity. One hundred sixty-six
      patients were identified who met the inclusion criteria. Of these, 89 patients
      received an HSCT before January 2007, during the time when patients received
      leukoreduced and CMV-negative blood products. Seventy-seven patients received an
      HSCT after this time, receiving only leukoreduced blood products. The 2 groups
      did not differ in terms of age, gender, diagnosis, graft type, graft source,
      conditioning regimen, or ABO compatibility (P > .05). CMV viremia was detected in
      3 patients who received CMV-negative leukoreduced blood products (3.37%) and in 1
      patient who received only leukoreduced blood products (1.30%, P = .6244). Of the
      patients who developed CMV viremia, 2 developed suspected CMV disease. Both of
      these patients were transfused with CMV-negative blood products. Secondary
      outcomes, including total length of stay in hospital, admission to the intensive
      care unit, acute and chronic graft versus host disease, and 100-day nonrelapse
      mortality, did not differ between the groups. In the era of universal
      leukoreduction of blood products, this study demonstrates that testing for CMV
      negative blood products is not needed for HSCT recipients.

PMID- 24099959
TI  - Incidence of cancer in a cohort of Spanish patients with systemic lupus
      erythematosus.
AB  - OBJECTIVE: To determine the incidence and prevalence of cancer in a cohort of
      patients with systemic lupus erythematosus (SLE) and identify associated risk
      factors. PATIENTS AND METHODS: The study comprised a dynamic cohort of SLE
      patients (November 1989 to December 2006) at a tertiary referral centre. An
      adjusted external control from the hospital tumour registry was used. RESULTS:
      The study included 175 SLE patients (90% women), with a mean time at risk of
      1370.5 patient-years. Fourteen women (8%) died, mainly from cardiovascular
      events. No patient died due to malignancy. We found 35 tumours in 28 patients, 25
      of them after the diagnosis of SLE, of which 5 were malignant. The rate of benign
      tumours was 14.6/1000 patient-years (95% CI, 8.9-22.5) and of malignant tumours
      3.6/1000 patient-years (95% CI, 1.5-8.8), with a crude incidence odds ratio for
      malignant tumours of 3.5 (95% CI, 1.5-7.9). However, this significance was lost
      after standardizing the rates. Concerning associated risk factors, differences
      were found in the mean erythrocyte sedimentation rate [HR 1.4 (1.1-1.7)], and the
      presence of thrombosis [HR 6.9 (1.49-41.2)], especially arterial thrombosis.
      CONCLUSIONS: We found a crude incidence rate of cancer that was almost four times
      greater in our SLE patients as compared with the expected rate in the hospital
      area of western Malaga.

PMID- 24099960
TI  - Health-related quality of life in psoriatic arthritis patients in Spain.
AB  - PURPOSE: To describe the demographic and clinical characteristics, including
      health-related quality-of-life (HRQL), in patients with psoriatic arthritis
      (PsA). METHODS: 287 patients from 18 Spanish centres were assessed. PsA severity
      was measured using the following criteria: (1) Psoriasis Area and Severity Index
      (PASI score 0-72, from low to high severity); (2) number of swollen and tender
      joints; and (3) Health Assessment Questionnaire (HAQ score 0-3 from low to high
      impairment in daily activities). HRQL assessment was performed using the
      following criteria: (a) EuroQol-5D (EQ-5D scores 1-3, with a higher score
      representing a worse HRQL), Visual Analogue Scale (VAS score 0-100, with a higher
      score representing a better HQRL) and (b) Short Form-36 (SF-36 score 0-100, with
      a higher score representing a better HRQL). RESULTS: 24.7% of patients were
      treated with infliximab. In the two groups, 55.7% of the patients were male with
      a mean age of 52.40+/-12.53 years. The average number of swollen joints was
      higher in patients not receiving biological therapy than in those receiving
      treatment (2.98 vs. 1.54). The mean PASI score was 3.73+/-5.83, and there was no
      difference between groups. HAQ scores were higher in patients receiving
      infliximab than in those not receiving treatment (0.93 vs. 0.70). The mean EQ-5D
      scores in the two groups indicated a poorer status based on pain and inability to
      perform usual/daily activities. HRQL measured by VAS score mean was 60.41 +/-
      20.08, and there was no difference between the groups. The domains in the SF-36
      suggesting poorer functioning in the two groups were the physical role (50.76 +/-
      43.43), physical pain (49.35 +/- 25.69) and the overall physical component (37.88
      +/- 10.87). CONCLUSIONS: PsA is associated with an impaired HRQL characterised by
      physical pain and poorer functioning in daily activities.

PMID- 24099961
TI  - Tocilizumab in patients with active rheumatoid arthritis and inadequate response
      to disease-modifying antirheumatic drugs or tumor necrosis factor inhibitors:
      subanalysis of Spanish results of an open-label study close to clinical practice.
AB  - OBJECTIVES: To analyze the Spanish experience in an international study which
      evaluated tocilizumab in patients with rheumatoid arthritis (RA) and an
      inadequate response to conventional disease-modifying antirheumatic drugs
      (DMARDs) or tumor necrosis factor inhibitors (TNFis) in a clinical practice
      setting. MATERIAL AND METHODS: Subanalysis of 170 patients with RA from Spain who
      participated in a phase IIIb, open-label, international clinical trial. Patients
      presented inadequate response to DMARDs or TNFis. They received 8mg/kg of
      tocilizumab every 4 weeks in combination with a DMARD or as monotherapy during 20
      weeks. Safety and efficacy of tocilizumab were analyzed. Special emphasis was
      placed on differences between failure to a DMARD or to a TNFi and the need to
      switch to tocilizumab with or without a washout period in patients who had
      previously received TNFi. RESULTS: The most common adverse events were infections
      (25%), increased total cholesterol (38%) and transaminases (15%). Five patients
      discontinued the study due to an adverse event. After six months of tocilizumab
      treatment, 71/50/30% of patients had ACR 20/50/70 responses, respectively. A
      higher proportion of TNFi-naive patients presented an ACR20 response: 76%
      compared to 64% in the TNFi group with previous washout and 66% in the TNFi group
      without previous washout. CONCLUSIONS: Safety results were consistent with
      previous results in patients with RA and an inadequate response to DMARDs or
      TNFis. Tocilizumab is more effective in patients who did not respond to
      conventional DMARDs than in patients who did not respond to TNFis.

PMID- 24099962
TI  - 5'-triphosphate-siRNA activates RIG-I-dependent type I interferon production and
      enhances inhibition of hepatitis B virus replication in HepG2.2.15 cells.
AB  - Hepatitis B virus (HBV) infection often results in acute or chronic viral
      hepatitis and other liver diseases including cirrhosis and hepatocellular
      carcinoma. Current therapies for HBV usually have severe side effects and can
      cause development of drug-resistant mutants. An alternative and safe
      immunotherapeutic approach for HBV infection is urgently needed for effective
      anti-HBV therapy. In this study, we propose a new strategy for anti-HBV therapy
      that activates type-I interferon (IFN) antiviral innate immunity through
      stimulating pattern-recognition receptors with RNA interference (RNAi) using a 5'
      end triphosphate-modified small interfering RNA (3p-siRNA). We designed and
      generated a 3p-siRNA targeting overlapping region of S gene and P gene of the HBV
      genome at the 5'-end of pregenomic HBV RNA. Our results demonstrated that 3p
      siRNA induced a RIG-I-dependent antiviral type-I IFN response when transfected
      into HepG2.2.15 cells that support HBV replication. The 3p-siRNA significantly
      inhibited HBsAg and HBeAg secretion from HepG2.2.15 cells in a RIG-I-dependent
      manner, and the antiviral effect of 3p-siRNA was superior to that of siRNA.
      Furthermore, 3p-siRNA had more pronounced inhibition effects on the replication
      of HBV DNA and the transcription of mRNA than that of siRNA. Finally, 3p-siRNA
      displayed antiviral activity with long-term suppression of HBV replication. In
      conclusion, our findings suggest that 3p-siRNA could act as a powerful
      bifunctional antiviral molecule with potential for developing a promising
      therapeutic against chronic HBV infection. 

PMID- 24099963
TI  - Diuretic effects of cannabinoid agonists in mice.
AB  - Cannabinoids both increase urine output and decrease urinary frequency in human
      subjects. However, these effects have not been systematically evaluated in intact
      mice, a species commonly used to evaluate the effects of novel cannabinoids. The
      present studies investigated whether cannabinoid agonists reliably produce
      diuresis in mice at doses comparable to those that produce other cannabinoid
      effects and, further, identified the receptors that may mediate these effects.
      Diuretic effects were measured in male mice over 6h. In some studies, urine was
      collected and analyzed for electrolyte measurements. In other studies, agonist
      injections were preceded by pretreatment with cannabinoid CB1 or CB2 selective
      antagonists, including a peripherally constrained CB1 antagonist. Companion
      studies evaluated the antinociceptive effects of the cannabinoid agonists in a
      warm-water tail-withdrawal assay. Direct-acting cannabinoid CB1 agonists Delta(9)
      tetrahydrocannabinol (THC), WIN 55,212, AM7418 and AM4054, had biphasic effects
      on diuresis, with peak diuretic effects occurring at lower doses than peak
      antinociceptive effects. Cannabinoid diuresis was similar to kappa-opioid agonist
      induced diuresis in terms of maximum effects with only moderate loss of Na(+).
      Antagonism studies indicate that the diuretic effects of cannabinoids are CB1
      receptor mediated, with both central and peripheral components. These findings
      suggest that mice may provide a model for understanding the mixed effects of
      marijuana on urine output, as described in clinical studies, and aid in the
      development of targeted cannabinoid based therapies for bladder dysfunction. 

PMID- 24099964
TI  - A statistical model of catheter motion from interventional x-ray images:
      application to image-based gating.
AB  - The motion and deformation of catheters that lie inside cardiac structures can
      provide valuable information about the motion of the heart. In this paper we
      describe the formation of a novel statistical model of the motion of a coronary
      sinus (CS) catheter based on principal component analysis of tracked electrode
      locations from standard mono-plane x-ray fluoroscopy images. We demonstrate the
      application of our model for the purposes of retrospective cardiac and
      respiratory gating of x-ray fluoroscopy images in normal dose x-ray fluoroscopy
      images, and demonstrate how a modification of the technique allows application to
      very low dose scenarios. We validated our method on ten mono-plane imaging
      sequences comprising a total of 610 frames from ten different patients undergoing
      radiofrequency ablation for the treatment of atrial fibrillation. For normal dose
      images we established systole, end-inspiration and end-expiration gating with
      success rates of 100%, 92.1% and 86.9%, respectively. For very low dose
      applications, the method was tested on the same ten mono-plane x-ray fluoroscopy
      sequences without noise and with added noise at signal to noise ratio (SNR)
      values of ?50, ?10, ?8, ?6, ?5, ?2 and ?1 to simulate the image quality of
      increasingly lower dose x-ray images. The method was able to detect the CS
      catheter even in the lowest SNR images with median errors not exceeding 2.6 mm
      per electrode. Furthermore, gating success rates of 100%, 71.4% and 85.7% were
      achieved at the low SNR value of ?2, representing a dose reduction of more than
      25 times. Thus, the technique has the potential to extract useful information
      whilst substantially reducing the radiation exposure. 

PMID- 24099965
TI  - Dosimetric comparison of different multileaf collimator leaves in treatment
      planning of intensity-modulated radiotherapy for cervical cancer.
AB  - To study the effect of multileaf collimator (MLC) leaf widths (standard MLC
      [sMLC] width of 10mm and micro-MLC [mMLC] width of 4mm) on intensity-modulated
      radiotherapy (IMRT) for cervical cancer. Between January 2010 and August 2010, a
      retrospective analysis was conducted on 12 patients with cervical cancer. The
      treatment plans for all patients were generated with the same machine setup
      parameters and optimization methods in a treatment planning system (TPS) based on
      2 commercial Elekta MLC devices. The dose distribution for the planning tumor
      volume (PTV), the dose sparing for organs at risk (OARs), the monitor units
      (MUs), and the number of IMRT segments were evaluated. For the delivery
      efficiency, the MUs were significantly higher in the sMLC-IMRT plan than in the
      mMLC-IMRT plan (802 +/- 56.9 vs 702 +/- 56.7; p < 0.05). The number of segments
      in the plans were 58.75 +/- 1.8 and 59 +/- 1.04 (p > 0.05). For the planning
      quality, the conformity index (CI) between the 2 paired IMRT plans with the mMLC
      and the sMLC did not differ significantly (average: 0.817 +/- 0.024 vs 0.810 +/-
      0.028; p > 0.05). The differences of the homogeneity index (HI) between the 2
      paired plans were statistically significant (average: 1.122 +/- 0.010 vs 1.132 +/
      0.014; p < 0.01). For OARs, the rectum, bladder, small intestine, and bony
      pelvis were evaluated in terms of V10, V20, V30, and V40, percentage of contoured
      OAR volumes receiving 10, 20, 30, and 40Gy, respectively, and the mean dose
      (Dmean) received. The IMRT plans with the mMLC protected the OARs better than the
      plans with the sMLC. There were significant differences (p < 0.05) in evaluated
      parameters between the 2 paired IMRT plans, except for V30 and V40 of the rectum
      and V10, V20, V40, and Dmean of the bladder. IMRT plans with the mMLC showed
      advantages over the plans with the sMLC in dose homogeneity for targets, dose
      sparing of OARs, and fewer MUs in cervical cancer. 

PMID- 24099966
TI  - Image-guided intensity-modulated radiotherapy for prostate cancer: Dose
      constraints for the anterior rectal wall to minimize rectal toxicity.
AB  - Rectal adverse events (AEs) are a major concern with definitive radiotherapy (RT)
      treatment for prostate cancer. The anterior rectal wall is at the greatest risk
      of injury as it lies closest to the target volume and receives the highest dose
      of RT. This study evaluated the absolute volume of anterior rectal wall receiving
      a high dose to identify potential ideal dose constraints that can minimize rectal
      AEs. A total of 111 consecutive patients with Stage T1c to T3a N0 M0 prostate
      cancer who underwent image-guided intensity-modulated RT at our institution were
      included. AEs were graded according to the Common Terminology Criteria for
      Adverse Events, version 4.0. The volume of anterior rectal wall receiving 5 to
      80Gy in 2.5-Gy increments was determined. Multivariable Cox regression models
      were used to identify cut points in these volumes that led to an increased risk
      of early and late rectal AEs. Early AEs occurred in most patients (88%); however,
      relatively few of them (13%) were grade >=2. At 5 years, the cumulative incidence
      of late rectal AEs was 37%, with only 5% being grade >=2. For almost all RT
      doses, we identified a threshold of irradiated absolute volume of anterior rectal
      wall above which there was at least a trend toward a significantly higher rate of
      AEs. Most strikingly, patients with more than 1.29, 0.73, or 0.45cm(3) of
      anterior rectal wall exposed to radiation doses of 67.5, 70, or 72.5Gy,
      respectively, had a significantly increased risk of late AEs (relative risks
      [RR]: 2.18 to 2.72; p <= 0.041) and of grade >= 2 early AEs (RR: 6.36 to 6.48; p
      = 0.004). Our study provides evidence that definitive image-guided intensity
      modulated radiotherapy (IG-IMRT) for prostate cancer is well tolerated and also
      identifies dose thresholds for the absolute volume of anterior rectal wall above
      which patients are at greater risk of early and late complications. 

PMID- 24099967
TI  - Molecular cloning and functional characterization of peptidoglycan recognition
      protein 6 in grass carp Ctenopharyngodon idella.
AB  - Peptidoglycan recognition proteins (PGRPs) are pattern recognition molecules of
      innate immunity. In this study, a long-form PGRP, designated as gcPGRP6, was
      identified from grass carp Ctenopharyngodon idella. The deduced amino acid
      sequence of gcPGRP6 is composed of 464 residues with a conserved PGRP domain at
      the C-terminus. The gcPGRP6 gene consists of four exons and three introns,
      spacing approximately 2.7 kb of genomic sequence. Phylogenetic analysis
      demonstrated that gcPGRP6 is clustered closely with zebrafish PGLYRP6, and formed
      a long-type PGRP subfamily together with PGLYRP2 members identified in teleosts
      and mammals. Real-time PCR and Western blotting analyses revealed that gcPGRP6 is
      constitutively expressed in organs/tissues examined, and its expression was
      significantly induced in liver and intestine of grass carp in response to PGN
      stimulation and in CIK cells treated with lipoteichoic acid (LTA), polyinosinic
      polycytidylic acid (Poly I:C) and peptidoglycan (PGN). Immunofluorescence
      microscopy and Western blotting analyses revealed that gcPGRP6 is effectively
      secreted to the exterior of CIK cells. The over-expression of gcPGRP6 in CIK
      cells leads to the activation of NF-kappaB and the inhibition of intracellular
      bacterial growth. Moreover, cell lysates from CIK cells transfected with pTurbo
      gcPGRP6-GFP plasmid display the binding activity towards Lys-type PGN from
      Staphylococcus aureus and DAP-type PGN from Bacillus subtilis. Furthermore,
      proinflammatory cytokine IL-2 and intracellular PGN receptor NOD2 had a
      significantly increased expression in CIK cells overexpressed with gcPGRP6. It is
      demonstrated that the PGRP6 in grass carp has a role in binding PGN, in
      inhibiting the growth of intracellular bacteria, and in activating NF-kappaB, as
      well as in regulating innate immune genes.

PMID- 24099968
TI  - Prevalence, patterns and predictors of substance use among Latino migrant men in
      a new receiving community.
AB  - BACKGROUND: The purpose of this study was to evaluate the prevalence, patterns
      and predictors (individual, social, cultural, and environmental) of illicit drug
      use and binge drinking in a cohort of Latino migrant men (LMM) in a new receiving
      community. METHODS: A cohort of LMM in New Orleans (n=125) was assembled in 2007
      using respondent driven sampling and interviewed quarterly for 18 months
      regarding past month substance use and other potential covariates. Baseline
      frequencies were weighted using RDSAT and longitudinal analyses included
      generalized estimating equations (GEE) and the Cochran-Armitage test for trends.
      RESULTS: At baseline, substance use behaviors were: drug use 15.0% (range 7.3
      25.0%) and binge drinking 58.3% (range 43.6-74.6%). All three of these behaviors
      decreased over follow-up (P<0.01). Baseline alcohol dependence and drug problem
      were 11.8% (range 5.6-24.3%) and 0.08% (range 0.00-2.7%) and both remained the
      same over time. Baseline rate of chlamydia was 9% (range 0.00-22.4%); all men
      tested negative for gonorrhea, HIV, and syphilis. For both binge drinking and
      drug use, having sex with a female sex worker was associated with increased risk,
      whereas belonging to a club or organization was associated with less risk.
      Additional factors associated with increased drug use were: having a friend in
      New Orleans upon arrival, symptoms of depression, and working in construction. An
      additional factor associated with less binge drinking was having family in New
      Orleans upon arrival. CONCLUSION: Among LMM, substance use is influenced by
      social and environmental factors. Interventions increase community connectedness
      may help decrease usage.

PMID- 24099970
TI  - Healthcare professionals' regard towards working with patients with substance use
      disorders: comparison of primary care, general psychiatry and specialist
      addiction services.
AB  - BACKGROUND: Healthcare professionals are crucial in access to treatment for
      patients with substance use disorders. However, healthcare professionals often
      have negative attitudes towards this patient group. Healthcare professionals'
      regard for working with patients with substance use disorders was examined and
      three sectors in which professionals are working were compared. METHODS: General
      practitioners (GPs; N=180), healthcare professionals of general psychiatry (N=89)
      and specialists in addiction services (N=78) filled out a questionnaire in which
      regard for working with patients with substance use disorders was assessed.
      ANOVAs were used to compare the sectors and multiple linear regression analysis
      tested the association of regard with attribution beliefs, emotional reactions
      and other characteristics of healthcare professionals. RESULTS: Regard for
      working with patients with substance use disorders was different between the
      three sectors (GPs M=42.00; general psychiatry M=48.18; addiction specialists
      M=55.41; p=0.00, omega(2)=0.40). Attribution of personal responsibility and
      feeling of anger and fear were associated with lower regard scores. More
      familiarity with substance use problems, higher frequency of working with this
      patients group and more confidence in substance abuse treatment were positively
      associated with regard. Social desirability bias was present and was positively
      related to healthcare professionals' regard. CONCLUSIONS: Health care
      professionals of specialist addiction services showed higher regard for working
      with patients with substance use disorders compared to professionals of general
      psychiatry services and GPs. Improvement of education and shared care models in
      which healthcare professionals are supported by professionals specializing in
      addiction might address low regard.

PMID- 24099969
TI  - C-reactive protein and substance use disorders in adolescence and early
      adulthood: a prospective analysis.
AB  - BACKGROUND: Dysregulated immune function and elevated inflammation markers are
      seen in adults with chronic diseases, including some psychiatric disorders, but
      evidence on inflammation in the case of drug abuse is conflicting. OBJECTIVE: To
      test the concurrent and predictive relations between C-reactive protein (CRP) and
      use and abuse of alcohol, nicotine and cannabis in a longitudinal, population
      sample of adolescents and young adults, at the period of highest increase in drug
      use. METHODS: Data from the prospective population-based Great Smoky Mountains
      Study (N=1420) were used, covering children in the community assessed at ages 9
      16, 19, and 21. Structured interviews were used to assess substance abuse
      symptoms and DSM-IV substance use disorders. Bloodspots were collected at each
      assessment and assayed for CRP. RESULTS: CRP levels were higher in the presence
      of nicotine, alcohol, and cannabis use and nicotine dependence. In prospective
      analyses, higher CRP levels predicted cannabis use and nicotine dependence, and
      nicotine use predicted higher CRP levels, once covariates were included in the
      models. Significant covariates were age, race (American Indian), and obesity.
      CONCLUSIONS: The inter-relationship of CRP and substance abuse has implications
      for the later health risks associated with early drug and alcohol use and abuse.

PMID- 24099971
TI  - Effects of hydrothermal liquefaction on the fate of bioactive contaminants in
      manure and algal feedstocks.
AB  - This study investigated the effects of hydrothermal liquefaction (HTL) on the
      fate of bioactive compounds (BACs) often present with wet biosolids from
      wastewater, manure, or algae. Tracking radiolabeled (14)C for two BACs showed
      that 60-79% of the carbon was transferred to the HTL raw oil product, and most of
      the rest was found in the aqueous product. In the presence of both swine manure
      and Spirulina biomass feedstocks, HTL provided essentially complete removal of
      three BACs when operated at 300 degrees C for >= 30 min. Experiments with both
      natural transformation and high-efficiency transformation showed that HTL
      provided complete deactivation of antibiotic resistant genes for all tested HTL
      conditions (250-300 degrees C, 15-60 min reaction time). Thus, incorporating HTL
      into wastewater treatment systems can simultaneously produce valuable bio-crude
      oil, provide effective removal of BACs and disrupt the natural pathways for
      antibiotic resistant gene transfer from manure and wastewater biosolids to the
      environment.

PMID- 24099972
TI  - Biosorption of uranium by melanin: kinetic, equilibrium and thermodynamic
      studies.
AB  - Limitation of conventional techniques for the removal of heavy metals present at
      low concentrations, has led to the need for developing alternate technologies
      like biosorption. In the present study we describe the use of melanin pigment
      synthesized through green technology, for sorption of uranium from aqueous
      system. Biosynthesized melanin showed good uptake over a broad pH range. Removal
      of uranium was rapid and equilibrium was reached within 2h of contact. It was
      observed that the kinetic data fits well into Lagergren's pseudo-second order
      equation. A maximum loading capacity of 588.24 mg g(-1) was calculated from
      Langmuir plot. Thermodynamic studies performed revealed that sorption process was
      favorable. Binding of uranium on the surface of melanin was confirmed by FT-IR
      and energy dispersive spectroscopy (EDS). Thus, biosynthesized melanin can be
      efficiently used as a sorbent for removal of uranium from aqueous solution.

PMID- 24099973
TI  - In situ investigation of processing property in combination with integration of
      microbial fuel cell and tubular membrane bioreactor.
AB  - Microbial fuel cell (MFC) presents a novel method for simultaneous energy
      recovery and wastewater treatment. In this study, a bio-cathode MFC with tubular
      membrane assembly was integrated to construct a MFC-TMBR system, which combined
      the advantages of each individual module. To examine the feasibility of MFC-TMBR
      integrated process, both electricity generation and wastewater treatment were
      investigated. Maximum voltage output of 0.8 V and maximum power density of 0.040
      W/m(2) were obtained in the 30th day of operation. The MFC-TMBR system achieved
      organic removal of 94%, as well as the ammonia nitrogen removal of more than 80%.
      Membrane fouling mitigation was realized using cross-flow filtration with tubular
      membrane in the MFC-TMBR, without any physical cleaning during the 30-day
      operation. Lower MLSS concentration and higher DO could potentially support this
      system. Low-cost materials were adopted for reactor construction. The results
      demonstrate that this system is an energy-efficient and cost-effective approach
      for wastewater treatment.

PMID- 24099974
TI  - NOx removal in chemical absorption-biological reduction integrated system:
      process rate and rate-limiting step.
AB  - Biological reduction of Fe(III)EDTA is considered as the key step that limits the
      removal efficiency of the chemical absorption-biological reduction integrated
      system. In this study, the process rates of each reaction step under typical
      conditions (T=50 degrees C, C FeII(EDTA)=1-5 mmol/L, CNO=0-500 ppm, CO2=1-10%,
      pH=7) were determined. Relevant kinetic constants including rate constants of
      absorption part and Michaelis-Menten kinetic constants of regeneration part were
      also obtained. On this basis, the theoretical process rates of each reaction step
      were predicted and compared in a steady state. The results confirmed that the
      removal rate of NO in this system is limited by the biological reduction of
      Fe(III)EDTA. Moreover, it indicated that increasing the concentration of total
      iron appropriately could enhance the bioreduction of Fe(III)EDTA.

PMID- 24099975
TI  - Characterization of nitrifying microbial community in a submerged membrane
      bioreactor at short solids retention times.
AB  - This study investigated the nitrifying bacterial community in membrane bioreactor
      (MBR) at short solids retention times (SRTs) of 3, 5 and 10 days. The denaturing
      gradient gel electrophoresis results showed that different types of ammonia
      oxidizing bacteria (AOB) can survive at different operating conditions. The
      diversity of AOB increased as the SRT increased. The real-time PCR results showed
      that the amoA gene concentrations were similar when MBRs were stabilized, and it
      can be a good indicator of stabilized nitrification. The results of clone library
      indicated that Nitrosomonas was the dominant group of AOB in three reactors. The
      microarray results showed that Nitrospira was the dominant group of nitrite
      oxidizing bacteria (NOB) in the system. All groups of AOB and NOB except
      Nitrosolobus and Nitrococcus were found in MBR, indicated that the nitrifying
      bacterial community structure was more complicated. The combination of some
      molecular tools can provide more information of microbial communities.

PMID- 24099976
TI  - Performance of Lead Integrity Alert to assist in the clinical diagnosis of
      implantable cardioverter defibrillator lead failures: analysis of different
      implantable cardioverter defibrillator leads.
AB  - BACKGROUND: The Lead Integrity Alert (LIA) was developed for Medtronic
      implantable cardioverter defibrillators to reduce inappropriate shocks for rapid
      oversensing caused by conductor fractures and reported for Medtronic Fidelis
      conductor fractures. The goal of this study was to compare the performance of LIA
      with conventional impedance monitoring for identifying lead system events (LSEs)
      and lead failures (LFs) in lead families that differ from Fidelis. METHODS AND
      RESULTS: We analyzed data from 12 793 LIA enabled implantable cardioverter
      defibrillator and lead combinations including 6123 St. Jude Riata or Durata, 5114
      Boston Scientific Endotak, and 1556 Fidelis combinations followed in the CareLink
      remote monitoring network for LSEs and LFs. Each alert was adjudicated based on
      implantable cardioverter-defibrillator stored electrograms/diagnostics and
      clinical data as an LSE or non-lead system event by 2 physicians after reviewing
      the electrograms and clinical data. During 13 562 patient-years of LIA follow-up,
      there were 179 adjudicated alerts, of which 84 were LSEs (including 65 LFs) and
      95 were non-lead system events. LIA identified >66% more LSE and >67% more LF
      compared with conventional impedance monitoring and did not differ by lead family
      for LSE (P=0.573) or LF (P=0.332). Isolated spikes on electrogram were associated
      more often with LF in St. Jude leads (71%) compared with Endotak (9%; P<0.001)
      and Fidelis leads (11%; P<0.001). The non-lead system event detection rate was
      different among lead families (P<0.001) ranging from 1 in every 78.5 years
      (Endotak), 228.9 years (St. Jude leads), and 627.6 years (Fidelis). CONCLUSIONS:
      LIA markedly increased the detection rate of LSE compared with conventional
      impedance monitoring.

PMID- 24099977
TI  - Automated MRI segmentation for individualized modeling of current flow in the
      human head.
AB  - OBJECTIVE: High-definition transcranial direct current stimulation (HD-tDCS) and
      high-density electroencephalography require accurate models of current flow for
      precise targeting and current source reconstruction. At a minimum, such modeling
      must capture the idiosyncratic anatomy of the brain, cerebrospinal fluid (CSF)
      and skull for each individual subject. Currently, the process to build such high
      resolution individualized models from structural magnetic resonance images
      requires labor-intensive manual segmentation, even when utilizing available
      automated segmentation tools. Also, accurate placement of many high-density
      electrodes on an individual scalp is a tedious procedure. The goal was to develop
      fully automated techniques to reduce the manual effort in such a modeling
      process. APPROACH: A fully automated segmentation technique based on Statical
      Parametric Mapping 8, including an improved tissue probability map and an
      automated correction routine for segmentation errors, was developed, along with
      an automated electrode placement tool for high-density arrays. The performance of
      these automated routines was evaluated against results from manual segmentation
      on four healthy subjects and seven stroke patients. The criteria include
      segmentation accuracy, the difference of current flow distributions in resulting
      HD-tDCS models and the optimized current flow intensities on cortical targets.
      MAIN RESULTS: The segmentation tool can segment out not just the brain but also
      provide accurate results for CSF, skull and other soft tissues with a field of
      view extending to the neck. Compared to manual results, automated segmentation
      deviates by only 7% and 18% for normal and stroke subjects, respectively. The
      predicted electric fields in the brain deviate by 12% and 29% respectively, which
      is well within the variability observed for various modeling choices. Finally,
      optimized current flow intensities on cortical targets do not differ
      significantly. SIGNIFICANCE: Fully automated individualized modeling may now be
      feasible for large-sample EEG research studies and tDCS clinical trials.

PMID- 24099978
TI  - Prospects for coitally-dependent hormonal contraception: perspectives from women
      in urban Kenya and Nigeria.
AB  - INTRODUCTION: Emergency contraceptive pills (ECPs) were developed and marketed
      with the emergency aspect firmly in mind, but research and anecdotal evidence
      indicate that some women use them as a form of regular contraception, spurring
      efforts in the reproductive health community to explore the development of a
      coitally-dependent oral contraceptive pill. METHODS: We asked women of
      reproductive age in Nairobi, Kenya and Lagos, Nigeria how likely they would be to
      use a hypothetical pericoital pill and why. RESULTS: Bivariate logistic
      regressions indicated that women aged 18-35 years, with secondary education or
      higher, and who had ever used condoms or short-acting methods, were more likely
      to say that they would use this hypothetical pill. Women who had ever used a
      family planning method or ECPs were also more likely to say they would use this
      pill. The likely adopters reported that they would use the pericoital method if
      it prevented pregnancy with little or no health problems and was convenient and
      easy to use. CONCLUSION: The findings suggest that should a safe and effective
      pericoital hormonal pill become available then a significant number of women
      would adopt this method.

PMID- 24099979
TI  - Age-related variation in sexual behaviours among heterosexual men residing in
      Brazil, Mexico and the USA.
AB  - OBJECTIVE: To compare the prevalence of demographic characteristics and sexual
      behaviours across age groups and to estimate their significance in predicting
      sexual risk factors by age cohort. METHODS: This cohort study examined sexually
      transmitted infection (STI) prevalence among heterosexual men in Brazil, Mexico
      and the USA (N=3047). Participants completed a sexual risk factor questionnaire
      and were tested for chlamydia, gonorrhoea, syphilis and genital herpes. We
      examined sexual risk in the study population through a composite measure of STI
      positivity by age cohort (young: 18-30 years; middle-aged: 31-44 years; older: 45
      70 years). Multivariable logistic regression models were used to generate
      adjusted odds ratios (AORs) and 95% confidence intervals (CIs). RESULTS: We found
      that STI positivity varied significantly by age group among heterosexual men by a
      number of covariates. In younger men, having more advanced education had a
      protective effect (16 years: AOR=0.37, 95% CI 0.15- 0.92), whereas higher numbers
      of sexual partners elevated the risk for STIs (20-49 partners: AOR=2.06, 95% CI
      1.04-4.06; >= 50 partners: AOR=4.33, 95% CI 1.74-10.76). Middle-aged men who were
      black (AOR=1.64, 95% CI 1.10-2.42) and divorced/separated/widowed (AOR=1.91, 95%
      CI 1.21-3.02) had an increased risk for a positive STI test. Among older men, a
      younger age at first vaginal sexual encounter (AOR=3.75, 95% CI 1.45-9.74) and a
      history of exchanging sex for money or drugs heightened STI risk (AOR=2.30, 95%
      CI 1.0-5.04). CONCLUSIONS: These findings demonstrate that age-related life
      experiences among heterosexual men influence sexual risk and STI transmission.
      This topic warrants further investigation to support the development and
      implementation of targeted interventions that may potentially reduce adverse
      sexual health outcomes.

PMID- 24099980
TI  - Effect of tolperisone on the resting brain and on evoked responses, an phMRI BOLD
      study.
AB  - Tolperisone is a voltage gated sodium channel blocker, centrally acting muscle
      relaxant drug, with a very advantageous side effect profile. Like other sodium
      channel blockers, it has weak affinity to the resting state and high affinity to
      the open/inactivated state of the channel. In this paper, its effect on BOLD
      responses in rat brain were elucidated both on the resting brain and paw
      stimulation evoked BOLD responses. Tolperisone did not exert any visible effect
      on resting brain, but strongly inhibited the paw stimulation evoked BOLD
      responses, showing somewhat higher efficacy in brain areas involved in pain
      sensation. This finding is in a good agreement with its sodium channel blocking
      profile. In the resting brain, most of the channels are in resting state.
      Electric train stimuli of the paw results in over activated neurons, where most
      sodium channels are in open or inactivated state. These data suggest that the
      very advantageous profile of tolperisone can be explained by its selective action
      on open or inactivated sodium channels of over-activated neurons in various brain
      regions rather than by a selective effect in the spinal cord as suggested
      previously. 

PMID- 24099981
TI  - A meta-analysis of treating acute traumatic brain injury with calcium channel
      blockers.
AB  - The purpose of this systematic review was to evaluate and meta-analyse the
      current evidence for the use of calcium channel blockers (CCBs) in the treatment
      of acute traumatic brain injury (TBI) and traumatic subarachnoid haemorrhage
      (tSAH). A systematic search of clinical trials.gov, Cochrane library databases,
      EMBASE, MEDLINE, Web of science search and WHO trial registry, plus hand
      searching of grey literature, was undertaken in March 2013. Two reviewers
      independently extracted the data using a pre-defined data extraction form. RevMan
      5 software was used to synthesise data and calculate the risk ratio (RR) based on
      event rates as well as the 95% confidence interval (CI). Finally, nine RCTs with
      a total of 2182 patients were included. Meta-analysis showed that there was no
      difference between CCBs and control groups for rates of mortality (n=1337, 5
      RCTs, RR 0.93 CI 0.77-1.12). In a subgroup tSAH analysis, the difference was not
      significant (n=389, 2 RCTs, RR 0.73 CI 0.53-1.02). There were slightly fewer
      unfavourable outcomes in the treatment group, but the difference was not
      statistically significant (n=2101, 8 RCTs, RR 0.90 CI 0.76-1.08). In the subgroup
      tSAH analysis, again, the difference did not reach statistical significance
      (n=1074, 5 RCTs, RR 0.95 CI 0.73-1.24). It seems that larger, well-designed RCTs
      are necessary in order to ascertain any clinical benefit CCBs may or may not have
      for the treatment of acute TBI. 

PMID- 24099982
TI  - Conservative management of an infected laparoscopic hernia mesh: A case study.
AB  - INTRODUCTION: A dreaded complication of laparoscopic hernia repair is infection
      of the mesh. Traditionally mesh infection is managed by surgical removal of the
      mesh, an extensive procedure resulting in high re-herniation rates. A technique
      to treat such infections whilst salvaging the mesh is sorely needed. We describe
      a case in which a laparoscopic mesh infection was treated solely with drainage,
      parenteral antibiotics and antibiotic irrigation of the mesh. PRESENTATION OF
      CASE: A 65 year old gentleman presented 11 months post laparoscopic repair of an
      inguinal hernia with malaise and an uncomfortable groin swelling. Computed
      tomography scanning revealed a collection surrounding the mesh which was drained
      and cultured to show heavy growth of Staphylococcus aureus. A pigtail drain on
      continuous drainage was inserted and kept in situ for 7 weeks. The patient
      received one week of intravenous flucloxacillin and two gentamycin irrigations
      through the drain as an inpatient. He then received 6 weeks of oral
      flucloxacillin and bi-weekly saline flushes through the drain in the community.
      By 12 weeks an ultrasound scan showed resolution of the collection. At 7 months
      he remains clinically free from recurrence. DISCUSSION: Here we report a novel
      conservative method used to treat a hernia mesh infection, preserve the mesh and
      avoid major surgery. Other reports exist suggesting variations in conservative
      methods to treat mesh infections, however ours is by far the most conservative.
      CONCLUSION: Clearly, further research is required to identify which method is
      most effective and in which patients it is likely to be successful.

PMID- 24099983
TI  - Disturbed B cell subpopulations and increased plasma cells in myasthenia gravis
      patients.
AB  - Whether there is a general perturbation of B and plasma cell subsets in
      myasthenia gravis (MG) has not been investigated so far. Here we performed a
      detailed flow cytometric analysis of blood and if available thymic tissue in
      order to detect MG-specific and therapy-induced changes. We observed significant
      differences in the distribution of B cell subsets in MG patients, yet these were
      mainly attributable to medical treatment. Furthermore MG is associated with
      significantly increased frequencies of plasma cells that were especially
      activated in purely ocular disease manifestation. In contrast to thymoma, B cell
      subset distribution in hyperplastic thymus could be distinguished from peripheral
      blood, however both tissues were not significantly enriched with plasma cells.
      Thus B cell differentiation in general is not defective in MG, but modified by
      therapy and enhanced frequencies of plasma cells can be detected in MG patients. 

PMID- 24099984
TI  - EBNA-1 IgG titers in Sardinian multiple sclerosis patients and controls.
AB  - Multiple sclerosis (MS) is thought to be triggered by environmental factors
      acting on a genetic predisposition. Sardinians share a homogeneous genetic
      background and boast one of the highest MS prevalence worldwide. We investigated
      Epstein-Barr virus (EBV) antibody prevalence in Sardinian population by ELISA.
      Our results show a higher serum prevalence of EBNA-1 IgG in MS patients compared
      to healthy controls. Moreover, analyzing a subset of patients treated for 6
      months with IFN-beta, we observed a decrease in their EBNA-1 specific IgG titers.
      These results confirm previous findings and strengthen the association between
      EBV and MS in Sardinia.

PMID- 24099986
TI  - Surgical outcomes in lung cancer presenting as ground-glass opacities of 3 cm or
      less: a review of 5 years' experience.
AB  - BACKGROUND: High-resolution computed tomography (HRCT) has become increasingly
      popular recently and more pulmonary ground-glass opacities (GGOs) are being
      identified. However, the treatment for these GGOs remains controversial. The
      purpose of this study was to retrospectively review the clinical and pathological
      characteristics and to demonstrate the longterm surgical outcomes in patients
      undergoing resection for GGOs in our institute. METHODS: From January 2004 to
      December 2008, we enrolled 50 patients undergoing resection for solitary
      pulmonary GGOs of 3 cm or less at Taipei Veterans General Hospital. Patients with
      a past history of lung cancer, or multiple GGOs at presentation, or GGOs
      accompanied by a solid component of more than 50 percent were excluded. The
      patients were retrospectively reviewed and the rate and circumstances of survival
      were analyzed. RESULTS: Of the 50 patients, 43 (86%) patients underwent surgery
      immediately after the GGO lesions were detected by the initial HRCT. Forty-six
      (92.0%) patients were diagnosed with lung cancer. Of this group, there were 8
      (17.4%) adenocarcinomas with lepidic predominant pattern, 13 (28.3%)
      adenocarcinomas with acinar predominant pattern, and 24 (52.2%) adenocarcinomas
      with papillary predominant pattern. There was one adenocarcinoma that was mixed
      with small cell carcinoma. There was no surgical mortality overall, and the 5
      year overall and disease-specific survival rates were 97.5% and 100%,
      respectively. CONCLUSION: The percentage of malignancy is high in pulmonary GGOs.
      Surgery results in an excellent prognosis in these patients.

PMID- 24099985
TI  - Mitochondrial abnormality associates with type-specific neuronal loss and cell
      morphology changes in the pedunculopontine nucleus in Parkinson disease.
AB  - Cholinergic neuronal loss in the pedunculopontine nucleus (PPN) associates with
      abnormal functions, including certain motor and nonmotor symptoms. This
      realization has led to low-frequency stimulation of the PPN for treating patients
      with Parkinson disease (PD) who are refractory to other treatment modalities.
      However, the molecular mechanisms underlying PPN neuronal loss and the
      therapeutic substrate for the clinical benefits following PPN stimulation remain
      poorly characterized, hampering progress toward designing more efficient
      therapies aimed at restoring the PPN's normal functions during progressive
      parkinsonism. Here, we investigated postmortem pathological changes in the PPN of
      PD cases. Our study detected a loss of neurons producing gamma-aminobutyric acid
      (GABA) as their output and glycinergic neurons, along with the pronounced loss of
      cholinergic neurons. These losses were accompanied by altered somatic cell size
      that affected the remaining neurons of all neuronal subtypes studied here.
      Because studies showed that mitochondrial dysfunction exists in sporadic PD and
      in PD animal models, we investigated whether altered mitochondrial composition
      exists in the PPN. A significant up-regulation of several mitochondrial proteins
      was seen in GABAergic and glycinergic neurons; however, cholinergic neurons
      indicated down-regulation of the same proteins. Our findings suggest an imbalance
      in the activity of key neuronal subgroups of the PPN in PD, potentially because
      of abnormal inhibitory activity and altered cholinergic outflow.

PMID- 24099987
TI  - Fluoxetine and suicidal ideation in minor depression.

PMID- 24099988
TI  - Effect of polystyrene and polyether imide cell culture inserts with different
      roughness on chondrocyte metabolic activity and gene expression profiles of
      aggrecan and collagen.
AB  - In vitro cultured autologous chondrocytes can be used for implantation to support
      cartilage repair. For this purpose, a very small number of autologous cells
      harvested from a biopsy have to be expanded in monolayer culture. Commercially
      available polymer surfaces lead to chondrocyte dedifferentiation. Hence, the
      demanding need for optimized polymers and surface topologies supporting
      chondrocytes' differentiated phenotypes in vitro arises. In this study we
      explored the effect of tailored cell culture plate inserts prepared from
      polystyrene (PS) and polyether imide (PEI) exhibiting three different roughness
      levels (R0, RI, RII) on chondrocyte morphology, metabolism and gene expression
      profile. As a control, commercially available tissue culture plastic (TCP) dishes
      were included. Primary porcine articular chondrocytes were seeded on tailored PS
      and PEI inserts with three different roughness levels. The metabolic activity of
      the chondrocytes was determined after 24 hours using alamar blue assay.
      Chondrocyte gene expression profiles (aggrecan, type I and type II collagen) were
      monitored after 48 hours using Real Time Detection (RTD)-PCR. Chondrocytes
      cultured on PS and PEI surfaces formed cell clusters after 24 and 48 hours, which
      was not observed on TCP. The metabolic activity of chondrocytes cultured on PS
      was lower than of chondrocytes cultured on PEI, but also lower than on TCP. Gene
      expression analyses revealed an elevated expression of cartilage-specific
      aggrecan and an impaired expression of both collagen types by chondrocytes on PS
      and PEI compared with TCP. In summary, PEI is a biocompatible biomaterial
      suitable for chondrocyte culturing, which can be further chemically
      functionalized for generating specific surface interactions or covalent binding
      of biomolecules. 

PMID- 24099989
TI  - Culture surface influence on T-cell phenotype and function.
AB  - When dealing with T lymphocyte culture there is currently very less information
      available about the interaction between T-cells and the culture system. In this
      study we look at the influence of the culture chamber on T-cell proliferation in
      two main aspects of the culture system, namely: culture chamber material and
      geometry. The study was carried out using unique polymeric closed cell culture
      inserts, which were processed via injection moulding from polystyrene (PS),
      polycarbonate (PC), polyetherurethane (PEU), polystyrene-co-acrylonitrile (PSAN)
      and polyetherimide (PEI). Furthermore culture chamber geometry was studied using
      commercially available 24, 12 and 6-well plates prepared from tissue culture
      plastic (TCP). For T lymphocyte stimulation two methods were used involving
      either EBV peptide pools or MACS iBead particles depending on the experiment
      performed. Culture was done with 1645 RPMI medium supplemented with foetal calf
      serum, penicillin, streptomycin and rhIL-2. We found four materials out of five
      we tested (PS, PC, PSAN and PEI) exhibited similar fold expansions with minimal
      influence on proportions of CD4 and CD8, while PEU had a negative influence on T
      cell growth along with adversely affected CD4/CD8 proportions. Changes in the
      geometry of TCP had no effect on T cell growth or maturation rather the size of
      geometry seems to have more influence on proliferation. T-cells appear to prefer
      smaller geometries during initial stages of culture while towards the end of the
      culture size becomes less significant to cell proliferation. The parameters
      tested in this study have significant influences on T-cell growth and are
      necessary to consider when designing and constructing expansion systems for
      antigen specific T lymphocytes. This is important when culturing T-cells for
      immunotherapeutic applications where antigen specificity, T-cell maturation and
      function should remain unaffected during culture. 

PMID- 24099990
TI  - miRNAs in brain development.
AB  - MicroRNAs (miRNAs) are small, non-coding RNAs that negatively regulate gene
      expression at the post-transcriptional level. In the brain, a large number of
      miRNAs are expressed and there is a growing body of evidence demonstrating that
      miRNAs are essential for brain development and neuronal function. Conditional
      knockout studies of the core components in the miRNA biogenesis pathway, such as
      Dicer and DGCR8, have demonstrated a crucial role for miRNAs during the
      development of the central nervous system. Furthermore, mice deleted for specific
      miRNAs and miRNA-clusters demonstrate diverse functional roles for different
      miRNAs during the development of different brain structures. miRNAs have been
      proposed to regulate cellular functions such as differentiation, proliferation
      and fate-determination of neural progenitors. In this review we summarise the
      findings from recent studies that highlight the importance of miRNAs in brain
      development with a focus on the mouse model. We also discuss the technical
      limitations of current miRNA studies that still limit our understanding of this
      family of non-coding RNAs and propose the use of novel and refined technologies
      that are needed in order to fully determine the impact of specific miRNAs in
      brain development. 

PMID- 24099991
TI  - Hyaluronan synthase 1 (HAS1) produces a cytokine-and glucose-inducible, CD44
      dependent cell surface coat.
AB  - Hyaluronan is a ubiquitous glycosaminoglycan involved in embryonic development,
      inflammation and cancer. In mammals, three hyaluronan synthase isoenzymes (HAS1
      3) inserted in the plasma membrane produce hyaluronan directly on cell surface.
      The mRNA level and enzymatic activity of HAS1 are lower than those of HAS2 and
      HAS3 in many cells, obscuring the importance of HAS1. Here we demonstrate using
      immunocytochemistry and transfection of fluorescently tagged HAS1 that its
      enzymatic activity depends on the ER-Golgi-plasma membrane traffic, like reported
      for HAS2 and HAS3. When cultured in 5 mM glucose, HAS1-transfected MCF-7 cells
      show very little cell surface hyaluronan, detected with a fluorescent hyaluronan
      binding probe. However, a large hyaluronan coat was seen in cells grown in 20 mM
      glucose and 1 mM glucosamine, or treated with IL-1beta, TNF-alpha, or TGF-beta.
      The coats were mostly removed by the presence of hyaluronan hexasaccharides, or
      Hermes1 antibody, indicating that they depended on the CD44 receptor, which is in
      a contrast to the coat produced by HAS3, remaining attached to HAS3 itself. The
      findings suggest that HAS1-dependent coat is induced by inflammatory agents and
      glycemic stress, mediated by altered presentation of either CD44 or hyaluronan,
      and can offer a rapid cellular response to injury and inflammation.

PMID- 24099992
TI  - Meta-analysis of data from animal studies: a practical guide.
AB  - Meta-analyses of data from human studies are invaluable resources in the life
      sciences and the methods to conduct these are well documented. Similarly there
      are a number of benefits in conducting meta-analyses on data from animal studies;
      they can be used to inform clinical trial design, or to try and explain
      discrepancies between preclinical and clinical trial results. However there are
      inherit differences between animal and human studies and so applying the same
      techniques for the meta-analysis of preclinical data is not straightforward. For
      example preclinical studies are frequently small and there is often substantial
      heterogeneity between studies. This may have an impact on both the method of
      calculating an effect size and the method of pooling data. Here we describe a
      practical guide for the meta-analysis of data from animal studies including
      methods used to explore sources of heterogeneity. 

PMID- 24099993
TI  - Pyrazole containing natural products: synthetic preview and biological
      significance.
AB  - A large number of structurally diverse natural compounds containing azole nucleus
      constitute an important class of biologically active heterocycles that are
      gaining more attention in the field of medicinal chemistry. Among azoles,
      pyrazoles are rarely found in nature probably due to difficulty in the formation
      of N-N bond by living organisms. However, they exhibit numerous biological
      activities, including anti-diabetic, antiviral, anticancer, anti-inflammatory,
      antibacterial and antifungal activities. The present review is an attempt to
      understand the chemistry along with medicinal importance of pyrazole containing
      natural products reported till date which would certainly help the scientific
      community to bring further developments in the isolation and synthetic
      methodologies for pyrazole based novel bioactive compounds. 

PMID- 24099994
TI  - Synthesis, cytotoxicity and DNA binding of oxoazabenzo[de]anthracenes derivatives
      in colon cancer Caco-2 cells.
AB  - New oxoazabenzo[de]anthracenes derivatives were synthesised and characterised.
      Their interactions with calf thymus DNA were studied by UV spectrophotometric
      analysis and a competitive ethidium bromide displacement assay. Cytotoxicity was
      determined by MTT assay, against colon adenocarcinoma (Caco-2 cells). Among all
      the oxoazabenzo[de]anthracenes derivatives reported herein only the piperidino
      derivative exhibited strong DNA binding properties and cytotoxic activity with
      IC50 values in the range of 16 +/- 1.5 MUM (72-h treatment). In addition, the
      piperidino derivative did not directly inhibit topoisomerase I and topoisomerase
      II enzymes. The results confirm that the presence of the
      oxoazabenzo[de]anthracenes together with the piperidino functionality is crucial
      in exerting DNA binding and cytotoxic properties, hence demonstrating promise as
      a chemical scaffold for further development of new anticancer agents.

PMID- 24099995
TI  - Monoamine oxidase inhibitory activity of 3,5-biaryl-4,5-dihydro-1H-pyrazole-1
      carboxylate derivatives.
AB  - Ethyl and phenyl carbamate derivatives of pyrazoline (3a-3h) were synthesized and
      tested for their MAO inhibitory activity. All the compounds were found to be
      selective towards MAO-A. Phenyl carbamates (3e-3h) were better than ethyl
      carbamates (3a-3d) and displayed the best selectivity index. Compound 3f (KiMAO
      A; 4.96 +/- 0.21 nM) was found to be equally potent as that of standard drug,
      Moclobemide (KiMAO-A; 5.01 +/- 0.13 nM) but with best selectivity index (8.86 *
      10(-5)). Molecular docking studies with R &S conformer of 3f revealed S
      enantiomer is better than R-enantiomer as reported earlier by other groups. It is
      proposed that VdW's radii of the substitution (bulkiness) in ring B determine the
      potency of phenyl carbamates.

PMID- 24099996
TI  - Novel nonsecosteroidal VDR agonists with phenyl-pyrrolyl pentane skeleton.
AB  - In order to find the vitamin D receptor (VDR) ligand whose VDR agonistic activity
      is separated from the calcemic activity sufficiently, novel nonsecosteroidal
      analogs with phenyl-pyrrolyl pentane skeleton were synthesized and evaluated for
      the VDR binding affinity, antiproliferative activity in vitro and serum calcium
      raising ability in vivo (tacalcitol used as control). Among them, several
      compounds showed varying degrees of VDR agonistic and growth inhibition
      activities of the tested cell lines. The most effective compound 2g (EC50: 1.06
      nM) exhibited stronger VDR agonistic activity than tacalcitol (EC50: 7.05 nM),
      inhibited the proliferations of HaCaT and MCF-7 cells with IC50 of 2.06 MUM and
      0.307 MUM (tacalcitol: 2.07 MUM and 0.057 MUM) and showed no significant effect
      on serum calcium.

PMID- 24099997
TI  - Novel promising linezolid analogues: rational design, synthesis and biological
      evaluation.
AB  - A new series of 5-substituted oxazolidinones derived from linezolid, having urea
      and thiourea moieties at the C-5 side chain of the oxazolidinone ring, were
      prepared and their in vitro antibacterial activity was evaluated. The compound
      10f demonstrated high antimicrobial activity, comparable to that of linezolid
      against Staphylococcus aureus.

PMID- 24099998
TI  - Coagulopathy in malaria.
AB  - Blood coagulation activation is frequently found in patients with malaria.
      Clinically apparent bleeding or disseminated intravascular coagulation (DIC) is
      associated with very severe disease and a high mortality. Protein C, protein S,
      and antithrombin levels were found to be low in P. falciparum, but were normal in
      P. vivax infection. Plasma levels of plasminogen activator inhibitor-1 were high
      in cases of P. falciparum infection whereas tissue plasminogen activator levels
      were low. Elevated plasma levels of von Willebrand factor (vWF) and vWF
      propeptide, thrombomodulin, endothelial microparticles have been reported in P.
      falciparum-infected patients. It has been demonstrated that severe P. falciparum
      infection is associated with acute endothelial cell (EC) activation, abnormal
      circulating ultralarge vWF multimers, and a significant reduction in plasma
      ADAMTS13 function. These changes may result in intravascular platelet
      aggregation, thrombocytopenia, and microvascular disease. It has also been shown
      that P. falciparum-parasitized red blood cells (pRBCs) induce tissue factor (TF)
      expression in microvascular ECs in vitro. Recently, loss of endothelial protein C
      receptor (EPCR) localized to sites of cytoadherent pRBCs in cerebral malaria has
      been demonstrated. Severe malaria is associated with parasite binding to EPCR.
      The cornerstone of the treatment of coagulopathy in malaria is the use of
      effective anti-malarial agents. DIC with spontaneous systemic bleeding should be
      treated with screened blood products. Study in Thailand has shown that for
      patients who presented with parasitemia >30% and severe systemic complications
      such as acute renal failure and ARDS, survival was superior in the group who
      received exchange transfusion. The use of heparin is generally restricted to
      patients with DIC and extensive deposition of fibrin, as occurs with purpura
      fulminans or acral ischemia. Antiplatelet agents interfere with the protective
      effect of platelets against malaria and should be avoided. 

PMID- 24099999
TI  - Using wilderness medical training as a recruitment tool and competence enhancer
      for nursing students at a rural nursing college in arctic Scandinavia.

PMID- 24100000
TI  - Endosymbiotic microorganisms in Adelges (Sacchiphantes) viridis (Insecta,
      Hemiptera, Adelgoidea: Adelgidae): Molecular characterization, ultrastructure and
      transovarial transmission.
AB  - The aim of this paper was to identify endosymbiotic microorganisms living in the
      body cavity of a Polish population of an aphid, Adelges (Sacchiphantes) viridis,
      as well as to describe their ultrastructure and mode of transmission between
      generations. Molecular data (amplification and sequencing of 16S rRNA genes)
      indicated that endosymbionts of A. (S.) viridis are Betaproteobacteria of the
      species "Candidatus Vallotia virida". Endosymbiotic bacteria are rod-shaped and
      localized in the cytoplasm of specific cells, termed bacteriocytes, of host
      insects. Endosymbionts sharing the same bacteriocytes differ in the density of
      their cytoplasm. There are two morphotypes of endosymbiotic bacteria: with
      electron-dense cytoplasm and electron-translucent cytoplasm. Since only bacteria
      containing electron-dense cytoplasm were observed in the binary fusion stage,
      differences in density of the cytoplasm are probably due to changes in the
      cytoskeleton of bacteria during division. Endosymbionts of A. (S.) viridis are
      transovarially (i.e. via oocytes) transmitted from the mother to the offspring. 

PMID- 24100001
TI  - Bis(4-benzyloxyphenyl)iodonium salts as effective precursors for the no-carrier
      added radiosynthesis of 4-[18F]fluorophenol.
AB  - 4-[18F]Fluorophenol is a very useful intermediate compound for building-up more
      complex molecules bearing a 4-[18F]fluorophenoxy moiety. Bis(4
      benzyloxyphenyl)iodonium salts proved very effective as labeling precursors for
      the radiosynthesis of this compound in no-carrier-added form. Starting from the
      bromide salt and performing the radiofluorination by conventional heating, 4
      [18F]fluorophenol was obtained in an overall RCY of 43 +/- 12% while a yield of
      52 +/- 3% was achieved more reliably starting from the tosylate salt and
      employing microwave heating.

PMID- 24100002
TI  - Newborn hearing concurrent genetic screening for hearing impairment-a clinical
      practice in 58,397 neonates in Tianjin, China.
AB  - OBJECTIVE: Newborn hearing screening (NHS) is used worldwide due to its
      feasibility and cost-efficiency. However, neonates with late-onset and
      progressive hearing impairment will be missed by NHS. Genetic factors account for
      an estimated 60% of congenital profound hearing loss. Our previous cohort studies
      were carried out in an innovative mode, i.e. hearing concurrent genetic
      screening, in newborns to improve the abilities or early diagnosis and
      intervention for the hearing defects. In this study, we performed the first
      clinical practice of this mode in Tianjin city. METHODS: A large cohort of 58,397
      neonates, born between December 2011 and December 2012, in 44 hospitals in
      Tianjin, were screened for 20 hot spot hearing loss associated mutations from
      GJB2, GJB3, SLC26A4 and MTRNR1(12S rRNA). The data of genetic screening results
      was comprehensively analyzed with newborn hearing screening (NHS) results.
      RESULTS: We developed an accurate, high throughput genetic screening method and
      applied it to a total of 58,397 newborns in Tianjin. 3225 (5.52%) infants were
      detected to carry at least one mutation allele in GJB2, GJB3, SLC26A4 or MTRNR1.
      34 (0.580/00) infants were positive for hearing loss caused by GJB2 or SLC26A4
      mutations (homozygote or compound heterozygote). 54(0.930/00) infants are
      heterozygous of various genes. 109(1.870/00) infants had the pathological
      mitochondrial DNA mutation. CONCLUSION: Accurate, comprehensive hearing loss
      associated genetic screening can facilitate genetic counseling and provides
      valuable prognostic information to affected infants. This united screening mode
      of this study was a promising clinical practice.

PMID- 24100003
TI  - Effect of adenoid hypertrophy on the voice and laryngeal mucosa in children.
AB  - INTRODUCTION: The adenoids, or pharyngeal tonsils, are lymphatic tissue localized
      at the mucous layer of the roof and posterior wall of nasopharynx. Dysphonia
      defined as perceptual audible change of a patient's habitual voice as self judged
      or judged by his or her listeners. The diagnosis of dysphonia relies on clinical
      judgment based on phoniatric symptoms, auditory perceptual assessment of voice
      (APA) and full laryngeal examination. PATIENTS AND METHODS: Our study was
      conducted to evaluate the effect of adenoid hypertrophy on voice and laryngeal
      mucosa. The study sample composed of sixty children, forty of them had adenoid
      hypertrophy (patient's group) and twenty healthy children (control group).
      Patient's group composed of 17 boys (42.5%) and 23 girls (57.5%), while control
      group consists of 8 males (40%) and 12 females (60%). All patients and control
      group subjected to history taking, clinical examination, lateral soft tissue X
      ray on the nasopharynx, APA based on the modified GRBAS scale and full laryngeal
      examination. The data are collected and analyzed statistically by using software
      SPSS. RESULTS: Our results showed that there is a significant association between
      adenoid hypertrophy and, degree of dysphonia, leaky voice, pitch of voice and
      laryngeal lesion. Adenoid hypertrophy did not associate with loudness of voice,
      as well as character (irregular, breathy and strained). Laryngeal lesions were
      detected in thirteen children from patient group (32.5%): nodules (n = 6),
      thickening (n = 5), congestion (n = 2), while one child only out of 20 children
      of the control group had congestion (5.0%). CONCLUSION: Our results showed the
      importance of the assessment of voice and laryngeal examination in patients with
      adenoid hypertrophy, also treating the minimal mucosal lesions that results from
      adenoid hypertrophy should be taken in consideration.

PMID- 24100004
TI  - Measuring internalized weight attitudes across body weight categories: validation
      of the modified weight bias internalization scale.
AB  - The purpose of this research was to validate a modified version of the Weight
      Bias Internalization Scale (WBIS-M) that is applicable to individuals across
      different body weight statuses. One hundred forty-eight men and women completed
      an online survey that included the WBIS-M and relevant measures of
      psychopathology. Results indicated that the WBIS-M had high internal consistency
      and strong construct validity. The WBIS-M also demonstrated significant
      correlations with body image, eating pathology, self-esteem, and symptoms of
      anxiety and depression, and was associated with these outcomes distinctly from
      antifat attitudes and body mass index. Implications for the use of this scale in
      diverse samples are discussed. 

PMID- 24100005
TI  - Evaluation of PMS-PCR technology for detection of Mycobacterium avium subsp.
      paratuberculosis directly from bovine fecal specimens.
AB  - Mycobacterium avium subsp. paratuberculosis (MAP) causes paratuberculosis, or
      Johne's disease, in animals. Diagnosis of MAP infection is challenging because of
      the pathogen's fastidious in vitro growth requirements and low-level intermittent
      shedding in feces during the preclinical phase of the infection. Detection of
      these "low-shedders" is important for effective control of paratuberculosis as
      these animals serve as sources of infection for susceptible calves. Magnetic
      separation technology, used in combination with culture or molecular methods for
      the isolation and detection of pathogenic bacteria, enhances the analytical
      sensitivity and specificity of detection methods. The aim of the present study
      was to evaluate peptide-mediated magnetic separation (PMS) capture technology
      coupled with IS900 PCR using the Roche real-time PCR system (PMS-PCR), in
      comparison with fecal culture using BACTEC-MGIT 960 system, for detection of MAP
      in bovine fecal samples. Among the 351 fecal samples 74.9% (263/351) were PMS-PCR
      positive while only 12.3% (43/351) were MGIT culture-positive (p=0.0001). All 43
      MGIT culture-positive samples were also positive by PMS-PCR. Mean PMS-PCR
      crossing-point (Cp) values for the 13 fecal samples with the highest number of
      MAP, based on time to detection, (26.3) were significantly lower than for the 17
      fecal samples with <100 MAP per 2g feces (30.06) (p<0.05). PMS-PCR technology
      provided results in a shorter time and yielded a higher number of positive
      results than MGIT culture. Earlier and faster detection of animals shedding MAP
      by PMS-PCR should significantly strengthen control efforts for MAP-infected
      cattle herds by helping to limit infection transmission at earlier stages of the
      infection. 

PMID- 24100007
TI  - Patient-centered outcomes research: a "new" research agenda.

PMID- 24100006
TI  - First detection of Schmallenberg virus RNA in bovine semen, Germany, 2012.
AB  - In analogy to the related Akabane virus, transmission of Schmallenberg virus
      (SBV) by contaminated semen has primarily been considered negligible. However,
      the potential economic consequences for stock-bull breeders prompted the
      investigation of reliable diagnostic methods for SBV-RNA detection in bovine
      semen. Twelve extraction methods were compared using a dilution series of SBV
      spiked semen as well as serum and medium samples for control. The most promising
      methods were subsequently used with semen samples obtained in an intensive field
      study. In total, frozen semen from 95 SBV-seroconverted bulls collected in the
      field between May and November 2012 were tested for SBV-RNA with an optimised
      standard operating procedure. The highest diagnostic and analytical sensitivity
      for the extraction of SBV in semen was found for the Trizol((r)) LS Reagent lysis
      with or without combined purification of the viral RNA with magnetic beads. A
      total of 29 of 766 semen batches from 11 of 95 SBV-infected bulls were PCR
      positive (Cq-values 26-37). Intermittent virus excretion was observed in 2 of the
      bulls. SBV-RNA-positive semen was coincidentally detected with early SBV
      antibodies in 4 bulls. In bulls that showed seroconversion together with
      consecutive positive semen batches, SBV-RNA was predominantly found in the
      seminal cell fraction, while in bulls with single positive results only, SBV-RNA
      was detected exclusively in the seminal plasma. 

PMID- 24100008
TI  - Overview of neonatal lupus.
AB  - Neonatal lupus (NL) is defined by the presentation of the fetus and the newborn
      who possess autoantibodies received from the mother. It is the dysfunction of the
      maternal immune system that leads to the production of autoantibodies to anti
      Sjogren syndrome-A, anti-Sjogren syndrome-B, and anti-ribonuclear protein
      antigens. These antibodies are shared through the placenta and produce bodily
      changes in the fetal skin and heart, as well as potential changes in other body
      systems. Congenital complete heart block is the most dangerous manifestation of
      NL that can occur in utero or after birth. This article will provide an overview
      the presentation of NL and current therapies. Prenatal steroids have been the
      mainstay of therapy to try to reverse first- and second-degree congenital heart
      block and to prevent progression to a more advanced stage. New therapies are
      combining steroids with intravenous immunoglobulin and plasmapheresis. This
      article will provide guidelines for practitioners so they can consider NL as a
      differential diagnosis when presented with cutaneous lesions, congenital heart
      block, or abnormal findings in the hematologic, hepatobiliary, neurologic, and
      musculoskeletal systems. 

PMID- 24100009
TI  - Female vibration discourages male courtship behaviour in the Amarillo fish
      (Girardinichthys multiradiatus).
AB  - Amarillo fish females (Girardinichthys multiradiatus) vibrate when conspecific
      males approach them; the reason behind this behaviour is unclear. Hypotheses are
      that females vibrate either to avoid aggression from males or to court them. We
      prevented females from vibrating by temporarily blocking their lateral line
      organs and eyes, on the assumption that they rely on these senses to detect
      approaching males. Females with the lateral line organs obstructed vibrated less
      frequently than females with the lateral line intact, indicating that the
      mechanosensory lateral line system is necessary for perceiving approaching males.
      Males displayed more courtship behaviour to sighted females with the lateral line
      organs obstructed than to sighted females with the lateral line intact. A general
      tendency indicated that the less the females vibrated the more the males courted
      them. These findings indicate that female vibration discourages male courtship
      behaviour. 

PMID- 24100011
TI  - Monosome formation during translation initiation requires the serine/arginine
      rich protein Npl3.
AB  - The yeast shuttling serine/arginine-rich protein Npl3 is required for the export
      of mRNAs and pre-60S ribosomal subunits from the nucleus to the cytoplasm. Here,
      we report a novel function of Npl3 in translation initiation. A mutation in its C
      terminus that prevents its dimerization (npl3Delta100) is lethal to cells and
      leads to translational defects, as shown by [(35)S]methionine incorporation
      assays and a hypersensitivity to the translational inhibitor cycloheximide.
      Moreover, this Npl3 mutant shows halfmers in polysomal profiles that are
      indicative of defects in monosome formation. Strikingly, the loss of the ability
      of Npl3 to dimerize does not affect mRNA and pre-60S export. In fact, the mRNA
      and rRNA binding capacities of npl3Delta100 and wild-type Npl3 are similar.
      Intriguingly, overexpression of the dimerization domain of Npl3 disturbs dimer
      formation and results in a dominant-negative effect, reflected in growth defects
      and a halfmer formation phenotype. In addition, we found specific genetic
      interactions with the ribosomal subunit joining factors Rpl10 and eukaryotic
      translation initiation factor 5B/Fun12 and detected a substantially decreased
      binding of npl3Delta100 to the Rpl10-containing complex. These findings indicate
      an essential novel function for Npl3 in the cytoplasm, which supports monosome
      formation for translation initiation. 

PMID- 24100010
TI  - Spt6 regulates intragenic and antisense transcription, nucleosome positioning,
      and histone modifications genome-wide in fission yeast.
AB  - Spt6 is a highly conserved histone chaperone that interacts directly with both
      RNA polymerase II and histones to regulate gene expression. To gain a
      comprehensive understanding of the roles of Spt6, we performed genome-wide
      analyses of transcription, chromatin structure, and histone modifications in a
      Schizosaccharomyces pombe spt6 mutant. Our results demonstrate dramatic changes
      to transcription and chromatin structure in the mutant, including elevated
      antisense transcripts at >70% of all genes and general loss of the +1 nucleosome.
      Furthermore, Spt6 is required for marks associated with active transcription,
      including trimethylation of histone H3 on lysine 4, previously observed in humans
      but not Saccharomyces cerevisiae, and lysine 36. Taken together, our results
      indicate that Spt6 is critical for the accuracy of transcription and the
      integrity of chromatin, likely via its direct interactions with RNA polymerase II
      and histones. 

PMID- 24100012
TI  - Intra- and intermolecular regulatory interactions in Upf1, the RNA helicase
      central to nonsense-mediated mRNA decay in yeast.
AB  - RNA helicases are involved in almost every aspect of RNA metabolism, yet very
      little is known about the regulation of this class of enzymes. In Saccharomyces
      cerevisiae, the stability and translational fidelity of nonsense-containing mRNAs
      are controlled by the group I RNA helicase Upf1 and the proteins it interacts
      with, Upf2 and Upf3. Combining the yeast two-hybrid system with genetic analysis,
      we show here that the cysteine- and histidine-rich (CH) domain and the RNA
      helicase domain of yeast Upf1 can engage in two new types of molecular
      interactions: an intramolecular interaction between these two domains and self
      association of each of these domains. Multiple observations indicate that these
      molecular interactions are crucial for Upf1 regulation. First, coexpression of
      the CH domain and the RNA helicase domain in trans can reconstitute Upf1 function
      in both promoting nonsense-mediated mRNA decay (NMD) and preventing nonsense
      suppression. Second, mutations that disrupt Upf1 intramolecular interaction cause
      loss of Upf1 function. These mutations weaken Upf2 interaction and, surprisingly,
      promote Upf1 self-association. Third, the genetic defects resulting from
      deficiency in Upf1 intramolecular interaction or RNA binding are suppressed by
      expression of Upf2. Collectively, these data reveal a set of sequential molecular
      interactions and their roles in regulating Upf1 function during activation of NMD
      and suggest that cis intramolecular interaction and trans self-association may be
      general mechanisms for regulation of RNA helicase functions. 

PMID- 24100013
TI  - Androgen induces a switch from cytoplasmic retention to nuclear import of the
      androgen receptor.
AB  - The androgen receptor (AR) has critical functions as a transcription factor in
      both normal and cancer cells, but the specific mechanisms that regulate its
      nuclear localization are not well defined. We found that an AR mutation commonly
      reported in prostate cancer generates an androgen-independent gain of function
      for nuclear import. The substitution, Thr877Ala, is within the ligand-binding
      domain, but the nuclear import gain of function is mediated by the bipartite
      nuclear localization signal (NLS) spanning the DNA-binding domain (DBD) and hinge
      region. Bipartite NLS activity depends on the structure provided by the DBD, and
      protein interactions with the bipartite NLS are repressed by the hinge region.
      The bipartite NLS is recognized by importin 7, a nuclear import receptor for
      several proteins. Importin 7 binding to AR, however, inhibits import by shielding
      the bipartite NLS. Androgen binding relieves the inhibition by inducing a switch
      that promotes exchange of importin 7 for karyopherin alpha import receptors.
      Importin 7 contributes to the regulation of AR import by restraining import until
      androgen is detected in the cytoplasm. 

PMID- 24100014
TI  - Tgif1 regulates quiescence and self-renewal of hematopoietic stem cells.
AB  - TG-interacting factor 1 (TGIF1) is a transcriptional repressor that can modulate
      retinoic acid and transforming growth factor beta signaling pathways. It is
      required for myeloid progenitor cell differentiation and survival, and mutations
      in the TGIF1 gene cause holoprosencephaly. Furthermore, we have previously
      observed that acute myelogenous leukemia (AML) patients with low TGIF1 levels had
      worse prognoses. Here, we explored the role of Tgif1 in murine hematopoietic stem
      cell (HSC) function. CFU assays showed that Tgif1(-/-) bone marrow cells produced
      more total colonies and had higher serial CFU potential. These effects were also
      observed in vivo, where Tgif1(-/-) bone marrow cells had higher repopulation
      potential in short- and long-term competitive repopulation assays than wild-type
      cells. Serial transplantation and replating studies showed that Tgif1(-/-) HSCs
      exhibited greater self-renewal and were less proliferative and more quiescent
      than wild-type cells, suggesting that Tgif1 is required for stem cells to enter
      the cell cycle. Furthermore, HSCs from Tgif1(+/-) mice had a phenotype similar to
      that of HSCs from Tgif1(-/-) mice, while bone marrow cells with overexpressing
      Tgif1 showed increased proliferation and lower survival in long-term transplant
      studies. Taken together, our data suggest that Tgif1 suppresses stem cell self
      renewal and provide clues as to how reduced expression of TGIF1 may contribute to
      poor long-term survival in patients with AML. 

PMID- 24100015
TI  - Extended self-renewal and accelerated reprogramming in the absence of Kdm5b.
AB  - Embryonic stem (ES) cell pluripotency is thought to be regulated in part by H3K4
      methylation. However, it is unclear how H3K4 demethylation contributes to ES cell
      function and participates in induced pluripotent stem (iPS) cell reprogramming.
      Here, we show that KDM5B, which demethylates H3K4, is important for ES cell
      differentiation and presents a barrier to the reprogramming process. Depletion of
      Kdm5b leads to an extension in the self-renewal of ES cells in the absence of
      LIF. Transcriptome analysis revealed the persistent expression of pluripotency
      genes and underexpression of developmental genes during differentiation in the
      absence of Kdm5b, suggesting that KDM5B plays a key role in cellular fate
      changes. We also observed accelerated reprogramming of differentiated cells in
      the absence of Kdm5b, demonstrating that KDM5B is a barrier to the reprogramming
      process. Expression analysis revealed that mesenchymal master regulators
      associated with the epithelial-to-mesenchymal transition (EMT) are downregulated
      during reprogramming in the absence of Kdm5b. Moreover, global analysis of
      H3K4me3/2 revealed that enhancers of fibroblast genes are rapidly deactivated in
      the absence of Kdm5b, and genes associated with EMT lose H3K4me3/2 during the
      early reprogramming process. These findings provide functional insight into the
      role for KDM5B in regulating ES cell differentiation and as a barrier to the
      reprogramming process. 

PMID- 24100016
TI  - Activated Cdc42-bound IQGAP1 determines the cellular endocytic site.
AB  - Recruitment of specific molecules to a specific membrane site is essential for
      communication between specialized membranous organelles. In the present study, we
      identified IQGAP1 as a novel GDP-bound-Rab27a-interacting protein. We found that
      IQGAP1 interacts with GDP-bound Rab27a when it forms a complex with GTP-bound
      Cdc42. We also found that IQGAP1 regulates the endocytosis of insulin secretory
      membranes. Silencing of IQGAP1 inhibits both endocytosis and the glucose-induced
      redistribution of endocytic machinery, including Rab27a and its binding protein
      coronin 3. These processes can also be inhibited by disruption of the trimeric
      complex with dominant negative IQGAP1 and Cdc42. These results indicate that
      activation of Cdc42 in response to the insulin secretagogue glucose recruits
      endocytic machinery to IQGAP1 at the cell periphery and regulates endocytosis at
      this membrane site. 

PMID- 24100017
TI  - Elements of the polycomb repressor SU(Z)12 needed for histone H3-K27 methylation,
      the interface with E(Z), and in vivo function.
AB  - Polycomb repressive complex 2 (PRC2) is an essential chromatin-modifying enzyme
      that implements gene silencing. PRC2 methylates histone H3 on lysine-27 and is
      conserved from plants to flies to humans. In Drosophila melanogaster, PRC2
      contains four core subunits: E(Z), SU(Z)12, ESC, and NURF55. E(Z) bears a SET
      domain that houses the enzyme active site. However, PRC2 activity depends upon
      critical inputs from SU(Z)12 and ESC. The stimulatory mechanisms are not
      understood. We present here functional dissection of the SU(Z)12 subunit. SU(Z)12
      contains two highly conserved domains: an ~140-amino-acid VEFS domain and a Cys2
      His2 zinc finger (ZnF). Analysis of recombinant PRC2 bearing VEFS domain
      alterations, including some modeled after leukemia mutations, identifies distinct
      elements needed for SU(Z)12 assembly with E(Z) and stimulation of histone
      methyltransferase. The results define an extensive VEFS subdomain that organizes
      the SU(Z)12-E(Z) interface. Although the SU(Z)12 ZnF is not needed for
      methyltransferase in vitro, genetic rescue assays show that the ZnF is required
      in vivo. Chromatin immunoprecipitations reveal that this ZnF facilitates PRC2
      binding to a genomic target. This study defines functionally critical SU(Z)12
      elements, including key determinants of SU(Z)12-E(Z) communication. Together with
      recent findings, this illuminates PRC2 modulation by conserved inputs from its
      noncatalytic subunits. 

PMID- 24100018
TI  - NF-kappaB1 inhibits NOD2-induced cytokine secretion through ATF3-dependent
      mechanisms.
AB  - Regulation of microbially induced cytokine secretion is critical in intestinal
      immune homeostasis. NOD2, the Crohn's disease-associated bacterial peptidoglycan
      sensor, activates the NF-kappaB pathway. After chronic NOD2 stimulation in human
      macrophages, cytokine secretion is significantly attenuated, similar to the
      situation in the intestinal environment. We find that NF-kappaB1 (p105/p50)
      expression is upregulated with chronic NOD2 stimulation and is required for
      attenuation of cytokine secretion in vitro in human macrophages and in vivo in
      mice. Upon chronic NOD2 stimulation, regulation of both activating (H3K4Me2 and
      H4Ac) and inhibitory (H3K27Me3) histone modifications was observed within
      cytokine gene promoters; these outcomes were NF-kappaB1 dependent. In addition to
      enhanced binding to cytokine gene promoters with chronic NOD2 stimulation, NF
      kappaB1 bound to the promoter of the transcriptional repressor, ATF3. ATF3 was
      then induced and bound to cytokine gene promoters; both features were impaired
      upon NF-kappaB1 knockdown. Restoring ATF3 expression under NF-kappaB1 knockdown
      conditions restored NOD2-mediated cytokine downregulation. Finally, NF-kappaB1
      and ATF3 cooperate with other inhibitory pathways, including IRAKM and secreted
      mediators, to downregulate cytokine secretion after chronic NOD2 stimulation.
      Therefore, we identify NF-kappaB1 and ATF3 as critical mechanisms through which
      NOD2 downregulates cytokines and contributes to intestinal immune homeostasis. 

PMID- 24100019
TI  - Reliability and accuracy of scout CT in the detection of vertebral fractures.
AB  - OBJECTIVE: The aim of the present study was to evaluate the reliability of scout
      CT (sCT) lateral radiograph, in terms of diagnostic accuracy and intra- and
      interobserver agreement in the detection of vertebral fractures (VFs). METHODS:
      300 CT examinations of the thoracic and/or lumbar spine were collected and
      independently analysed by 3 musculoskeletal radiologists in 2 different sessions.
      A semi-quantitative approach was used for VF assessment on sCT, and morphometric
      analysis was performed when a VF was suspected. Results of multiplanar sagittal
      CT reconstructions interpreted by the most expert radiologist were considered as
      gold standard. Arthrosis was also scored. Only vertebral bodies assessable by
      both sCT and gold standard were considered for the analysis. Area under the
      receiver operating characteristic curve (AUROC), Cohen's kappa statistic and
      linear-by-linear association were used for statistical analysis. RESULTS: 1522
      vertebrae were considered (130 males and 170 females; ages, 73.0+/-2.8 years). 73
      of 1522 (4.8%) VFs were identified in 34/300 patients (11.3%). In the detection
      of VFs, the sensitivity and specificity of sCT were 98.7% and 99.7%,
      respectively. Accuracy (AUROC=0.992+/-0.008), as well as interobserver agreement
      (k=0.968+/-0.008), was excellent. Intra-observer agreement was perfect (k=1.000).
      Performance of this method was independent of arthrosis, vertebral level and type
      and grade of VFs. CONCLUSION: sCT is a simple but very accurate method for the
      detection of VFs. It should be introduced as a spine evaluation tool for the
      detection of VFs in examinations that are performed for other diagnostic
      purposes. ADVANCES IN KNOWLEDGE: sCT lateral radiograph is an accurate tool for
      the detection of VFs. This technique may be used with several advantages in
      clinical practice.

PMID- 24100020
TI  - Antiobese function of platelet-activating factor: increased adiposity in platelet
      activating factor receptor-deficient mice with age.
AB  - Platelet-activating factor receptor (PAFR)-deficient mice developed a more severe
      obese state characterized by higher body mass (~25%) and epididymal fat mass
      (~55%) with age than that of wild-type (WT) littermates. PAFR-deficient mice did
      not show changes in the expression of critical genes involved in anabolic and
      catabolic metabolism in adipose, liver, and muscle tissues between 6 and 36 wk.
      However, a 38-81% reduction in beta3/beta1-adrenergic receptor (AR) and
      uncoupling protein 1 (UCP1) mRNA and protein levels was observed in the
      interscapular brown adipose tissue (BAT) of PAFR-deficient mice. Whereas a single
      injection of the beta3-adrenergic agonist, CL-316,243 (25 MUg/kg) increased
      temperatures in the brown fat and rectums of WT mice, this increase in
      temperature was markedly suppressed in PAFR-deficient mice. Acetyl-CoA:lyso
      platelet-activating factor (PAF) acetyltransferase, which is involved in PAF
      biosynthesis, and the PAF receptor were predominantly localized in BAT
      macrophages, whereas brown adipocytes possessed the enzyme and functional PAF
      receptors. The stimulation of brown adipocytes by PAF induced the expression of
      beta3-AR mRNA and protein (1.5- and 1.9-fold, respectively), but not that of
      UCP1. These results indicate that obesity in PAFR-deficient mice resulted from
      impaired BAT activity and suggest that the antiobese function of PAF occurs
      through beta3-AR/UCP1 expression in BAT.

PMID- 24100021
TI  - Brain-network mechanisms underlying the divergent effects of depression on
      spontaneous versus evoked pain in rats: a multiple single-unit study.
AB  - Studies have reported divergent behavioral effects of depression on spontaneous
      vs. stimulus-evoked pain. However, the underlying neurobiological mechanisms are
      still unclear. The present study used a depression model of unpredictable chronic
      mild stress (UCMS) and pain models for spontaneous pain (i.e., the formalin test)
      and acute evoked pain (i.e., noxious thermal stimulation) in rats. The activity
      of neurons within thalamo-cortical circuits in the lateral and medial pain
      pathways was recorded by a multiple-channel recording technique, and behaviors
      were observed simultaneously. The results confirmed our previous findings that
      rats exposed to UCMS tended to exhibit decreased pain sensitivity to experimental
      stimuli but increased behavioral responses to ongoing pain. Based on the analysis
      of single-unit responses, the results demonstrated that the processing of
      spontaneous vs. evoked pain in a depressive-like state was altered in the
      opposite direction (activation vs. inhibition). The ensemble encoding analysis
      revealed that exposure to UCMS gave rise to enhanced inter-regional functional
      connectivity in spontaneous pain processing, but did not influence that of evoked
      pain. In addition, different brain activation patterns underlying the processing
      of spontaneous vs. evoked pain were observed. These findings revealed that the
      distinct response patterns of neurons within the pain-related brain circuits,
      especially in the affective pain pathway, mediate the divergent effects of
      depression on spontaneous vs. evoked pain. This is also the first report on the
      electrophysiology of depression models that provides direct evidence that the
      effect of depression on spontaneous and evoked pain may involve different brain
      mechanisms. 

PMID- 24100022
TI  - Convergent effects of mouse Pet-1 deletion and human PET-1 variation on amygdala
      fear and threat processing.
AB  - Serotonin is critical for shaping the development of neural circuits regulating
      emotion. Pet-1 (FEV-1) is an ETS-domain transcription factor essential for
      differentiation and forebrain targeting of serotonin neurons. Constitutive Pet-1
      knockout (KO) causes major loss of serotonin neurons and forebrain serotonin
      availability, and behavioral abnormalities. We phenotyped Pet-1 KO mice for fear
      conditioning and extinction, and on a battery of assays for anxiety- and
      depression-related behaviors. Morphology of Golgi-stained neurons in basolateral
      amygdala (BLA) and prelimbic cortex was examined. Using human imaging genetics, a
      common variant (rs860573) in the PET-1 (FEV) gene was tested for effects on
      threat-related amygdala reactivity and psychopathology in 88 Asian-ancestry
      subjects. Pet-1 KO mice exhibited increased acquisition and expression of fear,
      and elevated fear recovery following extinction, relative to wild-type (WT). BLA
      dendrites of Pet-1 KO mice were significantly longer than in WT. Human PET-1
      variation associated with differences in amygdala threat processing and
      psychopathology. This novel evidence for the role of Pet-1 in fear processing and
      dendritic organization of amygdala neurons and in human amygdala threat
      processing extends a growing literature demonstrating the influence of genetic
      variation in the serotonin system on emotional regulation via effects on
      structure and function of underlying corticolimbic circuitry. 

PMID- 24100023
TI  - Transient impact of spike on theta rhythm in temporal lobe epilepsy.
AB  - Epileptic spike is an indicator of hyper-excitability and hyper-synchrony of
      neural networks. While cognitive deficit in epilepsy is a common observation, how
      spikes transiently influence brain oscillations, especially those essential for
      cognitive functions, remains obscure. Here we aimed to quantify the transient
      impacts of sporadic spikes on theta oscillations and investigate how such impacts
      may evolve during epileptogenesis. Longitudinal depth EEG data were recorded in
      the CA1 area of pilocarpine temporal lobe epilepsy (TLE) rat models. Phase
      stability, a measure of synchrony, and theta power were estimated around spikes
      as well as in the protracted spike-free periods (FP) at least 1h after spike
      bursts. We found that the change in theta power did not correlate with the change
      in phase stability. More importantly, the impact of spikes on theta rhythm was
      highly time-dependent. While theta power decreased abruptly after spikes both in
      the latent and chronic stages, changes of theta phase stability demonstrated
      opposite trends in the latent and chronic stages, potentially due to the
      substantial reorganization of neural circuits along epileptogenesis. During FP,
      theta phase stability was significantly higher than the baseline level before
      injections, indicating that hyper-synchrony remained even hours after the spike
      bursts. We concluded that spikes have transient negative effects on theta rhythm,
      however, impacts are different during latent and chronic stages, implying that
      its influence on cognitive processes may also change over time during
      epileptogenesis. 

PMID- 24100024
TI  - Efficacy and safety of ipilimumab 3mg/kg in patients with pretreated, metastatic,
      mucosal melanoma.
AB  - BACKGROUND: Mucosal melanoma is an extremely rare and aggressive malignancy that
      often remains undetected until it reaches an advanced stage, when effective
      treatment options are limited. The activity and safety of ipilimumab were
      assessed in an Expanded Access Programme (EAP) that included patients with
      metastatic, mucosal melanoma. METHODS: Ipilimumab was available upon physician
      request for patients aged ?16years with stage III (unresectable) or IV skin,
      ocular or mucosal melanoma, who had failed or did not tolerate previous
      treatments and had no other therapeutic option available. Patients received
      ipilimumab 3mg/kg every 3weeks for four doses. Patients with stable disease or an
      objective response to ipilimumab were eligible for retreatment upon disease
      progression. Tumour assessments were conducted at baseline and week 12 using
      immune-related response criteria. Patients were monitored for adverse events
      (AEs), including immune-related AEs, within 3 to 4days of each scheduled visit.
      RESULTS: Of 855 patients participating in the EAP in Italy, 71 (8%) had
      metastatic, mucosal melanoma. With a median follow-up of 21.8months, the response
      rate was 12% and the immune-related disease control rate was 36%. Median
      progression-free survival and overall survival were 4.3 and 6.4months,
      respectively. In total, 34% of patients reported treatment-related AEs of any
      grade, which were grade 3 or 4 in 9% of patients. AEs were generally manageable
      as per protocol-specific guidelines. CONCLUSION/INTERPRETATION: Ipilimumab may be
      a feasible treatment option in pretreated patients with metastatic mucosal
      melanoma, and warrants further investigation in prospective clinical trials.

PMID- 24100025
TI  - Accurate detection of upper tract urothelial carcinoma in tissue and urine by
      means of quantitative GDF15, TMEFF2 and VIM promoter methylation.
AB  - AIM OF THE STUDY: Upper tract urothelial carcinoma (UTUC) accounts for 5-10% of
      all urothelial tumours. It is mostly diagnosed at advanced stages, entailing a
      worse prognosis, owing to the lack of early and specific symptoms as well as of
      effective diagnostic tools. We previously identified a panel of epigenetic
      biomarkers (GDF15, TMEFF2 and VIM promoter methylation) that accurately
      identifies bladder cancer in urine. Herein, we assessed the performance of the
      same panel for UTUC detection and prognosis, in tissue and urine. MATERIAL AND
      METHODS: Methylation levels of reference and target genes were determined using
      real-time quantitative methylation-specific polymerase chain reaction (MSP) in
      bisulphite-modified DNA of 57 UTUC tissues, 36 normal upper tract urothelium
      (NUTUs), 22 urines from UTUC suspects and 20 urines from controls. Receiver
      operator characteristics (ROC)-curve analysis was performed to determine the
      performance of the biomarker panel and survival analyses were conducted to
      evaluate their prognostic value. RESULTS: Methylation levels of GDF15, TMEFF2 and
      VIM were significantly higher in UTUC compared to NUTUs (P=0.022; P<0.001;
      P<0.001, respectively). The panel accurately identified UTUC with 100% and 91%
      sensitivity, corresponding to an area under the curve of 1.000 and 0.923 in
      tissue and urines, respectively, with 100% specificity. Low VIM promoter
      methylation levels independently predicted poor disease-specific survival.
      CONCLUSIONS: GDF15, TMEFF2 and VIM promoter methylation allows for accurate
      identification of UTUC, in tissue and urine and VIM methylation provides relevant
      prognostic information, especially in high-stage disease. This assay may improve
      the clinical management of UTUC patients.

PMID- 24100026
TI  - Glycan-dependent and -independent interactions contribute to cellular substrate
      recruitment by calreticulin.
AB  - Calreticulin is an endoplasmic reticulum chaperone with specificity for
      monoglucosylated glycoproteins. Calreticulin also inhibits precipitation of
      nonglycosylated proteins and thus contains generic protein-binding sites, but
      their location and contributions to substrate folding are unknown. We show that
      calreticulin binds glycosylated and nonglycosylated proteins with similar
      affinities but distinct interaction kinetics. Although both interactions involve
      the glycan-binding site or its vicinity, the arm-like proline-rich (P-) domain of
      calreticulin contributes to binding non/deglycosylated proteins. Correspondingly,
      ensemble FRET spectroscopy measurements indicate that glycosylated and
      nonglycosylated proteins induce "open" and "closed" P-domain conformations,
      respectively. The co-chaperone ERp57 influences substrate-binding kinetics and
      induces a closed P-domain conformation. Together with analysis of the
      interactions of calreticulin with cellular proteins, these findings indicate that
      the recruitment of monoglucosylated proteins to calreticulin is kinetically
      driven, whereas the P-domain and co-chaperone contribute to stable substrate
      binding. Substrate sequestration in the cleft between the glycan-binding site and
      P-domain is a likely mechanism for calreticulin-assisted protein folding. 

PMID- 24100027
TI  - Structural basis for cyclization specificity of two Azotobacter type III
      polyketide synthases: a single amino acid substitution reverses their cyclization
      specificity.
AB  - Type III polyketide synthases (PKSs) show diverse cyclization specificity. We
      previously characterized two Azotobacter type III PKSs (ArsB and ArsC) with
      different cyclization specificity. ArsB and ArsC, which share a high sequence
      identity (71%), produce alkylresorcinols and alkylpyrones through aldol
      condensation and lactonization of the same polyketomethylene intermediate,
      respectively. Here we identified a key amino acid residue for the cyclization
      specificity of each enzyme by site-directed mutagenesis. Trp-281 of ArsB
      corresponded to Gly-284 of ArsC in the amino acid sequence alignment. The ArsB
      W281G mutant synthesized alkylpyrone but not alkylresorcinol. In contrast, the
      ArsC G284W mutant synthesized alkylresorcinol with a small amount of alkylpyrone.
      These results indicate that this amino acid residue (Trp-281 of ArsB or Gly-284
      of ArsC) should occupy a critical position for the cyclization specificity of
      each enzyme. We then determined crystal structures of the wild-type and G284W
      ArsC proteins at resolutions of 1.76 and 1.99 A, respectively. Comparison of
      these two ArsC structures indicates that the G284W substitution brings a steric
      wall to the active site cavity, resulting in a significant reduction of the
      cavity volume. We postulate that the polyketomethylene intermediate can be folded
      to a suitable form for aldol condensation only in such a relatively narrow cavity
      of ArsC G284W (and presumably ArsB). This is the first report on the alteration
      of cyclization specificity from lactonization to aldol condensation for a type
      III PKS. The ArsC G284W structure is significant as it is the first reported
      structure of a microbial resorcinol synthase. 

PMID- 24100029
TI  - Two-sided ubiquitin binding of NF-kappaB essential modulator (NEMO) zinc finger
      unveiled by a mutation associated with anhidrotic ectodermal dysplasia with
      immunodeficiency syndrome.
AB  - Hypomorphic mutations in the X-linked human NEMO gene result in various forms of
      anhidrotic ectodermal dysplasia with immunodeficiency. NEMO function is mediated
      by two distal ubiquitin binding domains located in the regulatory C-terminal
      domain of the protein: the coiled-coil 2-leucine zipper (CC2-LZ) domain and the
      zinc finger (ZF) domain. Here, we investigated the effect of the D406V mutation
      found in the NEMO ZF of an ectodermal dysplasia with immunodeficiency patients.
      This point mutation does not impair the folding of NEMO ZF or mono-ubiquitin
      binding but is sufficient to alter NEMO function, as NEMO-deficient fibroblasts
      and Jurkat T lymphocytes reconstituted with full-length D406V NEMO lead to
      partial and strong defects in NF-kappaB activation, respectively. To further
      characterize the ubiquitin binding properties of NEMO ZF, we employed di
      ubiquitin (di-Ub) chains composed of several different linkages (Lys-48, Lys-63,
      and linear (Met-1-linked)). We showed that the pathogenic mutation preferentially
      impairs the interaction with Lys-63 and Met-1-linked di-Ub, which correlates with
      its ubiquitin binding defect in vivo. Furthermore, sedimentation velocity and gel
      filtration showed that NEMO ZF, like other NEMO related-ZFs, binds mono-Ub and di
      Ub with distinct stoichiometries, indicating the presence of a new Ub site within
      the NEMO ZF. Extensive mutagenesis was then performed on NEMO ZF and
      characterization of mutants allowed the proposal of a structural model of NEMO ZF
      in interaction with a Lys-63 di-Ub chain. 

PMID- 24100028
TI  - Leptin regulates KATP channel trafficking in pancreatic beta-cells by a signaling
      mechanism involving AMP-activated protein kinase (AMPK) and cAMP-dependent
      protein kinase (PKA).
AB  - Pancreatic beta-cells secrete insulin in response to metabolic and hormonal
      signals to maintain glucose homeostasis. Insulin secretion is under the control
      of ATP-sensitive potassium (KATP) channels that play key roles in setting beta
      cell membrane potential. Leptin, a hormone secreted by adipocytes, inhibits
      insulin secretion by increasing KATP channel conductance in beta-cells. We
      investigated the mechanism by which leptin increases KATP channel conductance. We
      show that leptin causes a transient increase in surface expression of KATP
      channels without affecting channel gating properties. This increase results
      primarily from increased channel trafficking to the plasma membrane rather than
      reduced endocytosis of surface channels. The effect of leptin on KATP channels is
      dependent on the protein kinases AMP-activated protein kinase (AMPK) and PKA.
      Activation of AMPK or PKA mimics and inhibition of AMPK or PKA abrogates the
      effect of leptin. Leptin activates AMPK directly by increasing AMPK
      phosphorylation at threonine 172. Activation of PKA leads to increased channel
      surface expression even in the presence of AMPK inhibitors, suggesting AMPK lies
      upstream of PKA in the leptin signaling pathway. Leptin signaling also leads to F
      actin depolymerization. Stabilization of F-actin pharmacologically occludes,
      whereas destabilization of F-actin simulates, the effect of leptin on KATP
      channel trafficking, indicating that leptin-induced actin reorganization
      underlies enhanced channel trafficking to the plasma membrane. Our study uncovers
      the signaling and cellular mechanism by which leptin regulates KATP channel
      trafficking to modulate beta-cell function and insulin secretion. 

PMID- 24100030
TI  - Regulation of the Src-PP2A interaction in tumor necrosis factor (TNF)-related
      apoptosis-inducing ligand (TRAIL)-induced apoptosis.
AB  - TNF-related apoptosis-inducing ligand (TRAIL) selectively induces apoptosis in
      transformed and tumor cells but not in normal cells, making it a promising agent
      for cancer therapy. However, many cancer cells are resistant to TRAIL, and the
      underlying mechanisms are not fully understood. Here, we show that the regulation
      of the PP2A and Src interaction plays a critical role in TRAIL resistance.
      Specifically, we show that TRAIL treatment activates the tyrosine kinase Src,
      which subsequently phosphorylates caspase-8 at tyrosine 380, leading to the
      inhibition of caspase-8 activation. We also show that upon TRAIL treatment, Src,
      caspase-8, and PP2A/C (a catalytic subunit of the PP2A phosphatase) are
      redistributed into lipid rafts, a microdomain of the plasma membrane enriched
      with cholesterol, where PP2A dephosphorylates Src at tyrosine 418 and in turn
      inhibits caspase-8 phosphorylation. Furthermore, we find that TRAIL treatment
      causes PP2A/C degradation. These data suggest that the balance between Src
      mediated caspase-8 phosphorylation and the inactivation of Src-mediated caspase-8
      phosphorylation by PP2A determines the outcome of TRAIL treatment in breast
      cancer cells. Therefore, this work identifies a novel mechanism by which the
      interaction between PP2A and Src in the context of caspase-8 activation modulates
      TRAIL sensitivity in cancer cells. 

PMID- 24100031
TI  - The serine-threonine kinase inositol-requiring enzyme 1alpha (IRE1alpha) promotes
      IL-4 production in T helper cells.
AB  - The inositol-requiring enzyme 1alpha (IRE1alpha) is a serine-threonine kinase
      that plays crucial roles in activating the unfolded protein response. Studies
      suggest that IRE1alpha is activated during thymic T cell development and in
      effector CD8(+) T cells. However, its role in regulating T helper cell
      differentiation remains unknown. We find that IRE1alpha is up-regulated and
      activated upon CD4(+) T cell activation and plays an important role in promoting
      cytokine IL-4 production. CD4(+) T cells from IRE1alpha KO mice have reduced IL-4
      protein expression, and this impaired IL-4 production is not due to the altered
      expression of Th2 lineage-specific transcription factors, such as GATA3. Instead,
      IL-4 mRNA stability is reduced in IRE1alpha KO T cells. Furthermore, treatment of
      T cells with an IRE1alpha-specific inhibitor, 4MU8C, leads to a block in IL-4, IL
      5, and IL-13 production, confirming the role of IRE1alpha in the regulation of IL
      4. This study identifies a regulatory function for IRE1alpha in the promotion of
      IL-4 in T cells. 

PMID- 24100032
TI  - Identifying key amino acid residues that affect alpha-conotoxin AuIB inhibition
      of alpha3beta4 nicotinic acetylcholine receptors.
AB  - alpha-Conotoxin AuIB is a selective alpha3beta4 nicotinic acetylcholine receptor
      (nAChR) subtype inhibitor. Its analgesic properties are believed to result from
      it activating GABAB receptors and subsequently inhibiting CaV2.2 voltage-gated
      calcium channels. The structural determinants that mediate diverging AuIB
      activity at these targets are unknown. We performed alanine scanning mutagenesis
      of AuIB and alpha3beta4 nAChR, homology modeling, and molecular dynamics
      simulations to identify the structural determinants of the AuIB.alpha3beta4 nAChR
      interaction. Two alanine-substituted AuIB analogues, [P6A]AuIB and [F9A]AuIB, did
      not inhibit the alpha3beta4 nAChR. NMR and CD spectroscopy studies demonstrated
      that [F9A]AuIB retains its native globular structure, so its activity loss is
      probably due to loss of specific toxin-receptor residue pairwise contacts.
      Compared with AuIB, the concentration-response curve for inhibition of
      alpha3beta4 by [F9A]AuIB shifted rightward more than 10-fold, and its subtype
      selectivity profile changed. Homology modeling and molecular dynamics simulations
      suggest that Phe-9 of AuIB interacts with a two-residue binding pocket on the
      beta4 nAChR subunit. This hypothesis was confirmed by site-directed mutagenesis
      of the beta4-Trp-59 and beta4-Lys-61 residues of loop D, which form a putative
      binding pocket. AuIB analogues with Phe-9 substitutions corroborated the finding
      of a binding pocket on the beta4 subunit and gave further insight into how AuIB
      Phe-9 interacts with the beta4 subunit. In summary, we identified critical
      residues that mediate interactions between AuIB and its cognate nAChR subtype.
      These findings might help improve the design of analgesic conopeptides that
      selectively "avoid" nAChR receptors while targeting receptors involved with
      nociception. 

PMID- 24100033
TI  - CO2/HCO3(-)- and calcium-regulated soluble adenylyl cyclase as a physiological
      ATP sensor.
AB  - The second messenger molecule cAMP is integral for many physiological processes.
      In mammalian cells, cAMP can be generated from hormone- and G protein-regulated
      transmembrane adenylyl cyclases or via the widely expressed and structurally and
      biochemically distinct enzyme soluble adenylyl cyclase (sAC). sAC activity is
      uniquely stimulated by bicarbonate ions, and in cells, sAC functions as a
      physiological carbon dioxide, bicarbonate, and pH sensor. sAC activity is also
      stimulated by calcium, and its affinity for its substrate ATP suggests that it
      may be sensitive to physiologically relevant fluctuations in intracellular ATP.
      We demonstrate here that sAC can function as a cellular ATP sensor. In cells, sAC
      generated cAMP reflects alterations in intracellular ATP that do not affect
      transmembrane AC-generated cAMP. In beta cells of the pancreas, glucose
      metabolism generates ATP, which corresponds to an increase in cAMP, and we show
      here that sAC is responsible for an ATP-dependent cAMP increase. Glucose
      metabolism also elicits insulin secretion, and we further show that sAC is
      necessary for normal glucose-stimulated insulin secretion in vitro and in vivo. 

PMID- 24100034
TI  - Proapoptotic Bax and Bak proteins form stable protein-permeable pores of tunable
      size.
AB  - The Bcl-2 proapoptotic proteins Bax and Bak mediate the permeabilization of the
      mitochondrial outer membrane during apoptosis. Current models consider that Bax
      and Bak form pores at the mitochondrial outer membrane that are responsible for
      the release of cytochrome c and other larger mitochondrial apoptotic factors
      (i.e. Smac/DIABLO, AIF, and endoglycosidase G). However, the properties and
      nature of Bax/Bak apoptotic pores remain enigmatic. Here, we performed a detailed
      analysis of the membrane permeabilizing activity of Bax and Bak at the single
      vesicle level. We directly visualized that cBid-activated Bax and BakDeltaC21 can
      form membrane pores large enough to release not only cytochrome c, but also
      allophycocyanine, a protein of 104 kDa. Interestingly, the size of Bax and
      BakDeltaC21 pores is not constant, as typically observed in purely proteinaceous
      channels, but evolves with time and depends on protein concentration. We found
      that Bax and BakDeltaC21 formed long-lived pores, whose areas changed with the
      amount of Bax/BakDeltaC21 but not with cardiolipin concentration. Altogether, our
      results demonstrate that Bax and BakDeltaC21 follow similar mechanisms of
      membrane permeabilization characterized by the formation of protein-permeable
      pores of dynamic size, in agreement with the proteolipidic nature of these
      apoptotic pores. 

PMID- 24100035
TI  - Mitochondrial dysfunction and permeability transition in osteosarcoma cells
      showing the Warburg effect.
AB  - Metabolic reprogramming in cancer is manifested by persistent aerobic glycolysis
      and suppression of mitochondrial function and is known as the Warburg effect. The
      Warburg effect contributes to cancer progression and is considered to be a
      promising therapeutic target. Understanding the mechanisms used by cancer cells
      to suppress their mitochondria may lead to development of new approaches to
      reverse metabolic reprogramming. We have evaluated mitochondrial function and
      morphology in poorly respiring LM7 and 143B osteosarcoma (OS) cell lines showing
      the Warburg effect in comparison with actively respiring Saos2 and HOS OS cells
      and noncancerous osteoblastic hFOB cells. In LM7 and 143B cells, we detected
      markers of the mitochondrial permeability transition (MPT), such as mitochondrial
      swelling, depolarization, and membrane permeabilization. In addition, we detected
      mitochondrial swelling in human OS xenografts in mice and archival human OS
      specimens using electron microscopy. The MPT inhibitor sanglifehrin A reversed
      MPT markers and increased respiration in LM7 and 143B cells. Our data suggest
      that the MPT may play a role in suppression of mitochondrial function,
      contributing to the Warburg effect in cancer. 

PMID- 24100036
TI  - A network of interdependent molecular interactions describes a higher order Nrd1
      Nab3 complex involved in yeast transcription termination.
AB  - Nab3 and Nrd1 are yeast heterogeneous nuclear ribonucleoprotein (hnRNP)-like
      proteins that heterodimerize and bind RNA. Genetic and biochemical evidence
      reveals that they are integral to the termination of transcription of short non
      coding RNAs by RNA polymerase II. Here we define a Nab3 mutation (nab3Delta134)
      that removes an essential part of the protein's C terminus but nevertheless can
      rescue, in trans, the phenotype resulting from a mutation in the RNA recognition
      motif of Nab3. This low complexity region of Nab3 appears intrinsically
      unstructured and can form a hydrogel in vitro. These data support a model in
      which multiple Nrd1-Nab3 heterodimers polymerize onto substrate RNA to effect
      termination, allowing complementation of one mutant Nab3 molecule by another
      lacking a different function. The self-association property of Nab3 adds to the
      previously documented interactions between these hnRNP-like proteins, RNA
      polymerase II, and the nascent transcript, leading to a network of nucleoprotein
      interactions that define a higher order Nrd1-Nab3 complex. This was underscored
      from the synthetic phenotypes of yeast strains with pairwise combinations of Nrd1
      and Nab3 mutations known to affect their distinct biochemical activities. The
      mutations included a Nab3 self-association defect, a Nab3-Nrd1 heterodimerization
      defect, a Nrd1-polymerase II binding defect, and an Nab3-RNA recognition motif
      mutation. Although no single mutation was lethal, cells with any two mutations
      were not viable for four such pairings, and a fifth displayed a synthetic growth
      defect. These data strengthen the idea that a multiplicity of interactions is
      needed to assemble a higher order Nrd1-Nab3 complex that coats specific nascent
      RNAs in preparation for termination. 

PMID- 24100037
TI  - Direct measurements of oscillatory glycolysis in pancreatic islet beta-cells
      using novel fluorescence resonance energy transfer (FRET) biosensors for pyruvate
      kinase M2 activity.
AB  - Pulses of insulin released from pancreatic beta-cells maintain blood glucose in a
      narrow range, although the source of these pulses is unclear. We and others have
      proposed that positive feedback mediated by the glycolytic enzyme
      phosphofructokinase-1 (PFK1) enables beta-cells to generate metabolic
      oscillations via autocatalytic activation by its product fructose 1,6
      bisphosphate (FBP). Although much indirect evidence has accumulated in favor of
      this hypothesis, a direct measurement of oscillating glycolytic intermediates has
      been lacking. To probe glycolysis directly, we engineered a family of inter- and
      intramolecular FRET biosensors based on the glycolytic enzyme pyruvate kinase M2
      (PKAR; pyruvate kinase activity reporter), which multimerizes and is activated
      upon binding FBP. When introduced into Min6 beta-cells, PKAR FRET efficiency
      increased rapidly in response to glucose. Importantly, however, metabolites
      entering downstream of PFK1 (glyceraldehyde, pyruvate, and ketoisocaproate)
      failed to activate PKAR, consistent with sensor activation by FBP; the dependence
      of PKAR on FBP was further confirmed using purified sensor in vitro. Using a
      novel imaging modality for monitoring mitochondrial flavin fluorescence in mouse
      islets, we show that slow oscillations in mitochondrial redox potential
      stimulated by 10 mm glucose are in phase with glycolytic efflux through PKM2,
      measured simultaneously from neighboring islet beta-cells expressing PKAR. These
      results indicate that PKM2 activity in beta-cells is oscillatory and are
      consistent with pulsatile PFK1 being the mediator of slow glycolytic
      oscillations. 

PMID- 24100038
TI  - The inhibitory effects of a rhamnogalacturonan I (RG-I) domain from ginseng
      pectin on galectin-3 and its structure-activity relationship.
AB  - Pectin has been shown to inhibit the actions of galectin-3, a beta-galactoside
      binding protein associated with cancer progression. The structural features of
      pectin involved in this activity remain unclear. We investigated the effects of
      different ginseng pectins on galectin-3 action. The rhamnogalacturonan I-rich
      pectin fragment, RG-I-4, potently inhibited galectin-3-mediated hemagglutination,
      cancer cell adhesion and homotypic aggregation, and binding of galectin-3 to T
      cells. RG-I-4 specifically bound to the carbohydrate recognition domain of
      galectin-3 with a dissociation constant of 22.2 nm, which was determined by
      surface plasmon resonance analysis. The structure-activity relationship of RG-I-4
      was investigated by modifying the structure through various enzymatic and
      chemical methods followed by activity tests. The results showed that (a) galactan
      side chains were essential to the activity of RG-I-4, whereas arabinan side
      chains positively or negatively regulated the activity depending on their
      location within the RG-I-4 molecule. (b) The activity of galactan chain was
      proportional to its length up to 4 Gal residues and largely unchanged thereafter.
      (c) The majority of galactan side chains in RG-I-4 were short with low
      activities. (d) The high activity of RG-I-4 resulted from the cooperative action
      of these side chains. (e) The backbone of the molecule was very important to RG-I
      4 activity, possibly by maintaining a structural conformation of the whole
      molecule. (f) The isolated backbone could bind galectin-3, which was insensitive
      to lactose treatment. The novel discovery that the side chains and backbone play
      distinct roles in regulating RG-I-4 activity is valuable for producing highly
      active pectin-based galectin-3 inhibitors. 

PMID- 24100039
TI  - Tyrosyl radicals in dehaloperoxidase: how nature deals with evolving an oxygen
      binding globin to a biologically relevant peroxidase.
AB  - Dehaloperoxidase (DHP) from Amphitrite ornata, having been shown to catalyze the
      hydrogen peroxide-dependent oxidation of trihalophenols to dihaloquinones, is the
      first oxygen binding globin that possesses a biologically relevant peroxidase
      activity. The catalytically competent species in DHP appears to be Compound ES, a
      reactive intermediate that contains both a ferryl heme and a tyrosyl radical. By
      simulating the EPR spectra of DHP activated by H2O2, Thompson et al. (Thompson,
      M. K., Franzen, S., Ghiladi, R. A., Reeder, B. J., and Svistunenko, D. A. (2010)
      J. Am. Chem. Soc. 132, 17501-17510) proposed that two different radicals,
      depending on the pH, are formed, one located on either Tyr-34 or Tyr-28 and the
      other on Tyr-38. To provide additional support for these simulation-based
      assignments and to deduce the role(s) that tyrosyl radicals play in DHP, stopped
      flow UV-visible and rapid-freeze-quench EPR spectroscopic methods were employed
      to study radical formation in DHP when three tyrosine residues, Tyr-28, Tyr-34,
      and Tyr-38, were replaced either individually or in combination with
      phenylalanines. The results indicate that radicals form on all three tyrosines in
      DHP. Evidence for the formation of DHP Compound I in several tyrosine mutants was
      obtained. Variants that formed Compound I showed an increase in the catalytic
      rate for substrate oxidation but also an increase in heme bleaching, suggesting
      that the tyrosines are necessary for protecting the enzyme from oxidizing itself.
      This protective role of tyrosines is likely an evolutionary adaptation allowing
      DHP to avoid self-inflicted damage in the oxidative environment. 

PMID- 24100040
TI  - Identification of global ferredoxin interaction networks in Chlamydomonas
      reinhardtii.
AB  - Ferredoxins (FDXs) can distribute electrons originating from photosynthetic water
      oxidation, fermentation, and other reductant-generating pathways to specific
      redox enzymes in different organisms. The six FDXs identified in Chlamydomonas
      reinhardtii are not fully characterized in terms of their biological function. In
      this report, we present data from the following: (a) yeast two-hybrid screens,
      identifying interaction partners for each Chlamydomonas FDX; (b) pairwise yeast
      two-hybrid assays measuring FDX interactions with proteins from selected
      biochemical pathways; (c) affinity pulldown assays that, in some cases, confirm
      and even expand the interaction network for FDX1 and FDX2; and (d) in vitro
      NADP(+) reduction and H2 photo-production assays mediated by each FDX that verify
      their role in these two pathways. Our results demonstrate new potential roles for
      FDX1 in redox metabolism and carbohydrate and fatty acid biosynthesis, for FDX2
      in anaerobic metabolism, and possibly in state transition. Our data also suggest
      that FDX3 is involved in nitrogen assimilation, FDX4 in glycolysis and response
      to reactive oxygen species, and FDX5 in hydrogenase maturation. Finally, we
      provide experimental evidence that FDX1 serves as the primary electron donor to
      two important biological pathways, NADPH and H2 photo-production, whereas FDX2 is
      capable of driving these reactions at less than half the rate observed for FDX1. 

PMID- 24100041
TI  - Identification of Wilms' tumor 1-associating protein complex and its role in
      alternative splicing and the cell cycle.
AB  - Wilms' tumor 1-associating protein (WTAP) is a putative splicing regulator that
      is thought to be required for cell cycle progression through the stabilization of
      cyclin A2 mRNA and mammalian early embryo development. To further understand how
      WTAP acts in the context of the cellular machinery, we identified its interacting
      proteins in human umbilical vein endothelial cells and HeLa cells using shotgun
      proteomics. Here we show that WTAP forms a novel protein complex including Hakai,
      Virilizer homolog, KIAA0853, RBM15, the arginine/serine-rich domain-containing
      proteins BCLAF1 and THRAP3, and certain general splicing regulators, most of
      which have reported roles in post-transcriptional regulation. The depletion of
      these respective components of the complex resulted in reduced cell proliferation
      along with G2/M accumulation. Double knockdown of the serine/arginine-rich (SR)
      like proteins BCLAF1 and THRAP3 by siRNA resulted in a decrease in the nuclear
      speckle localization of WTAP, whereas the nuclear speckles were intact.
      Furthermore, we found that the WTAP complex regulates alternative splicing of the
      WTAP pre-mRNA by promoting the production of a truncated isoform, leading to a
      change in WTAP protein expression. Collectively, these findings show that the
      WTAP complex is a novel component of the RNA processing machinery, implying an
      important role in both posttranscriptional control and cell cycle regulation. 

PMID- 24100042
TI  - Crystal structure of anti-polysialic acid antibody single chain Fv fragment
      complexed with octasialic acid: insight into the binding preference for
      polysialic acid.
AB  - Polysialic acid is a linear homopolymer of alpha2-8-linked sialic acids attached
      mainly onto glycoproteins. Cell surface polysialic acid plays roles in cell
      adhesion and differentiation events in a manner that is often dependent on the
      degree of polymerization (DP). Anti-oligo/polysialic acid antibodies have DP
      dependent antigenic specificity, and such antibodies are widely utilized in
      biological studies for detecting and distinguishing between different
      oligo/polysialic acids. A murine monoclonal antibody mAb735 has a unique
      preference for longer polymers of polysialic acid (DP >10), yet the mechanism of
      recognition at the atomic level remains unclear. Here, we report the crystal
      structure of mAb735 single chain variable fragment (scFv735) in complex with
      octasialic acid at 1.8 A resolution. In the asymmetric unit, two scFv735
      molecules associate with one octasialic acid. In both complexes of the unit, all
      the complementarity-determining regions except for L3 interact with three
      consecutive sialic acid residues out of the eight. A striking feature of the
      complex is that 11 ordered water molecules bridge the gap between antibody and
      ligand, whereas the direct antibody-ligand interaction is less extensive. The
      dihedral angles of the trisialic acid unit directly interacting with scFv735 are
      not uniform, indicating that mAb735 does not strictly favor the previously
      proposed helical conformation. Importantly, both reducing and nonreducing ends of
      the bound ligand are completely exposed to solvent. We suggest that mAb735 gains
      its apparent high affinity for a longer polysialic acid chain by recognizing
      every three sialic acid units in a paired manner. 

PMID- 24100043
TI  - Midwives' views on appropriate antenatal counselling for congenital anomaly
      tests: do they match clients' preferences?
AB  - OBJECTIVE: this study aims to provide insight into: (a) midwives' views on
      appropriate antenatal counselling for congenital anomaly tests, and (b) whether
      these views match clients' preferences regarding antenatal counselling. DESIGN: a
      comparative (midwives versus clients) questionnaire survey. Cognitive interviews
      (n=8) were used to validate the internal validity of the midwifery questionnaire
      results. PARTICIPANTS AND SETTING: 1416 Dutch midwives (response 62%) completed a
      questionnaire measuring their views on appropriate antenatal counselling for
      congenital anomaly tests. MEASUREMENTS: we used the 58-item midwives' version of
      the QUOTE (prenatal), an instrument to assess clients' counselling preferences.
      Descriptive statistics were used to explore midwives' views on appropriate
      counselling and how these relate to client preferences as measured previously
      with the clients' version of the QUOTE (prenatal). FINDINGS: almost all midwives
      consider the client-midwife relation (100%) and health education (95%) to be
      (very) important for appropriate antenatal counselling for congenital anomaly
      tests. Almost half of the midwives consider decision-making support (47%) to be
      (very) important. These findings are practically congruent with client
      preferences. Still, clinically relevant differences were found regarding 13
      individual items, e.g. more clients than midwives value 'medical information
      about congenital anomalies' and 'getting advice whether to take prenatal tests or
      not'. KEY CONCLUSION: like clients, most midwives value a good client-midwife
      relation and health education as (very) important for antenatal counselling for
      congenital anomaly tests. Less than half of them value decision-making support.
      These findings are in contrast with the literature in which decision-making
      support is seen as the most important part of antenatal counselling for
      congenital anomaly tests. IMPLICATION FOR PRACTICE: preferably, antenatal
      counselling for congenital anomaly tests should be consistent with the three
      function model of antenatal counselling i.e. maintaining a client-midwife
      relation, providing health education as well as decision-making support, and
      tailored to clients' individual preferences. As not all midwives subscribe to
      these functions, reflection on their views is important. Furthermore, midwives
      need to bridge their views on appropriate antenatal counselling and client
      preferences. To do so, midwives may benefit from the Shared Decision Making
      approach.

PMID- 24100044
TI  - Local arterial stiffening assessed by MRI precedes atherosclerotic plaque
      formation.
AB  - BACKGROUND: Atherosclerosis is known to impair vascular function and cause
      vascular stiffening. The aim of this study was to evaluate the potential
      predictive role of vascular stiffening in the early detection of atherosclerosis.
      Therefore, we investigated the time course of early functional and morphological
      alterations of the vessel wall in a murine atherosclerosis model. Because initial
      lesions are distributed inhomogeneously in early-stage atherosclerosis, MR
      microscopy was performed to measure vascular elasticity locally, specifically the
      local pulse wave velocity and the arterial wall thickness. METHODS AND RESULTS:
      Local pulse wave velocity and the mean arterial wall thickness were determined in
      the ascending and the abdominal aortae of ApoE(-/-) and wild-type mice. In vivo
      MRI revealed that baseline pulse wave velocity and morphology were similar in 6
      week-old ApoE(-/-) and WT mice, whereas at the age of 18 weeks, local pulse wave
      velocity was significantly elevated in ApoE(-/-) mice. Significantly increased
      vessel wall thickness was not found in ApoE(-/-) mice until the age of 30 weeks.
      Histological analysis of the aortae of ApoE(-/-) and WT mice showed that
      increased pulse wave velocity coincided with the fragmentation of the elastic
      laminae in the arterial wall, which is hypothesized to induce early vascular
      stiffening and may be promoted by macrophage-mediated matrix degradation.
      CONCLUSIONS: We newly report that the assessment of local pulse wave velocity via
      MRI provides early information about the local progression of atherosclerosis
      before macroscopic alterations of the vessel wall occur.

PMID- 24100045
TI  - Aortic valve area, stroke volume, left ventricular hypertrophy, remodeling, and
      fibrosis in aortic stenosis assessed by cardiac magnetic resonance imaging:
      comparison between high and low gradient and normal and low flow aortic stenosis.
AB  - BACKGROUND: Recent works using echocardiography suggested that low gradient (LG),
      low flow (LF) aortic stenosis (AS) has more pronounced left ventricular (LV)
      concentric remodeling, smaller LV cavity size, and more interstitial fibrosis
      compared with high gradient (HG) normal flow (NF) AS. Therefore, we evaluated the
      accuracy of echocardiographic measurements and compared remodeling and fibrosis
      in different types of AS by cardiac magnetic resonance (CMR). METHODS AND
      RESULTS: A total of 128 patients (73+/-11 years of age; 75 men) with aortic valve
      area (AVA) <0.6 cm(2)/m(2) and ejection fraction >50% by echocardiography
      underwent CMR to measure planimetric AVA, phase-contrast indexed stroke volume,
      LV mass, and focal fibrosis. Using <40 mm Hg and indexed stroke volume <35
      mL/m(2) by echocardiography as criteria for LG and LF, 69 (54%) patients were
      HG/NF, 28 (22%) HG/LF, 17 (13%) LG/NF, and 14 (11%) LG/LF AS. LV outflow tract
      area, indexed stroke volume, and AVA correlated well between echocardiography and
      CMR (r=0.7, 0.61, and 0.65, respectively; P<0.001 for all). By CMR, however,
      planimetric AVA was larger in LF/LG (0.54+/-0.08 cm(2)/m(2)) and LG/NF (0.61+/
      0.08 cm(2)/m(2)) than in HG/LF (0.46+/-0.07 cm(2)/m(2); P<0.05) AS, and indexed
      LV mass was lower in LG/LF (75+/-12 g/m(2)) and LG/NF (81+/-18 g/m(2)) than in
      HG/LF (100+/-27 g/m(2); P<0.05) AS. All groups of AS had similar LV volumes,
      predominantly concentric hypertrophy remodeling, and similar amounts of focal
      fibrosis. CONCLUSIONS: CMR confirmed overall accuracy of echocardiographic
      classification of AS but demonstrated that LG/LF and LG/NF AS have larger AVA,
      less LV hypertrophy, and similar focal fibrosis compared with HG/LF AS. This
      challenges the view that LG/LF AS is a more advanced state of AS.

PMID- 24100046
TI  - Effect of combined systolic and diastolic functional parameter assessment for
      differentiation of cardiac amyloidosis from other causes of concentric left
      ventricular hypertrophy.
AB  - BACKGROUND: Differentiation of cardiac amyloidosis (CA) from other causes of
      concentric left ventricular hypertrophy remains a clinical challenge, especially
      in patients with preserved ejection fraction at the early disease stages. METHODS
      AND RESULTS: Consecutive hypertrophic patients with CA, isolated arterial
      hypertension, Fabry disease, and Friedreich ataxia (n=25 per group) were
      investigated; 25 healthy volunteers served as a control group. Standard
      echocardiography was performed, and segmental longitudinal peak systolic strain
      (LSsys) in the septum was assessed by 2-dimensional speckle tracking imaging.
      Indices of left ventricular hypertrophy and ejection fraction were similar among
      all patient groups. Deceleration time of early filling was significantly lower in
      patients with CA (147+/-46 milliseconds) compared with those with isolated
      arterial hypertension, Fabry disease, or control subjects (all P<0.0125). Septal
      basal LSsys (-6+/-2%) was significantly lower in patients with CA compared with
      those with isolated arterial hypertension (-14+/-6%), Fabry disease (-12+/-5%),
      Friedreich ataxia (-16+/-2%), or control subjects (-17+/-3%; all P<0.001),
      whereas septal apical LSsys was similar among all patient groups and control
      subjects (all P>0.05). A data-driven cutoff value for the ratio of septal apical
      to basal LSsys ratio >2.1 differentiated CA from other causes of left ventricular
      hypertrophy (sensitivity, 88%; specificity, 85%; positive predictive value, 67%;
      negative predictive value, 96%). The prevalence of septal apical to basal LSsys
      ratio >2.1 plus deceleration time of early filling <200 milliseconds was 88% in
      CA but 0% in all other groups. CONCLUSIONS: A systolic septal longitudinal base
      to-apex strain gradient (septal apical to basal LSsys ratio >2.1), combined with
      a shortened diastolic deceleration time of early filling (deceleration time of
      early filling <200 milliseconds), aids in differentiating CA from other causes of
      concentric left ventricular hypertrophy.

PMID- 24100047
TI  - Towards autonomous neuroprosthetic control using Hebbian reinforcement learning.
AB  - OBJECTIVE: Our goal was to design an adaptive neuroprosthetic controller that
      could learn the mapping from neural states to prosthetic actions and
      automatically adjust adaptation using only a binary evaluative feedback as a
      measure of desirability/undesirability of performance. APPROACH: Hebbian
      reinforcement learning (HRL) in a connectionist network was used for the design
      of the adaptive controller. The method combines the efficiency of supervised
      learning with the generality of reinforcement learning. The convergence
      properties of this approach were studied using both closed-loop control
      simulations and open-loop simulations that used primate neural data from robot
      assisted reaching tasks. MAIN RESULTS: The HRL controller was able to perform
      classification and regression tasks using its episodic and sequential learning
      modes, respectively. In our experiments, the HRL controller quickly achieved
      convergence to an effective control policy, followed by robust performance. The
      controller also automatically stopped adapting the parameters after converging to
      a satisfactory control policy. Additionally, when the input neural vector was
      reorganized, the controller resumed adaptation to maintain performance.
      SIGNIFICANCE: By estimating an evaluative feedback directly from the user, the
      HRL control algorithm may provide an efficient method for autonomous adaptation
      of neuroprosthetic systems. This method may enable the user to teach the
      controller the desired behavior using only a simple feedback signal.

PMID- 24100048
TI  - Microbial formation and degradation of oxygen-containing polycyclic aromatic
      hydrocarbons (OPAHs) in soil during short-term incubation.
AB  - We tested whether OPAHs were formed during 19-wk incubation of a fertile soil at
      optimum moisture in the dark. The soil had initial mean (+/-s.e., n = 3)
      concentrations of 22 +/- 1.7 (Sigma28PAHs) and 4.2 +/- 0.34 MUg g(-1)
      (Sigma14OPAHs). After 19 wk, individual PAH and OPAH concentrations had decreased
      by up to 14 and 37%, respectively. Decreases in % of initial concentrations were
      positively correlated with their KOW values for PAHs (r = 0.48, p = 0.022) and 9
      OPAHs (r = 0.78, p = 0.013) but negatively, albeit not significantly, for 5 OPAHs
      (r = -0.75, p = 0.145) suggesting net formation of some OPAHs. The latter was
      supported by significantly increasing 1-indanone/fluorene ratios while the other
      OPAH to parent-PAH ratios remained constant or tended to increase. We conclude
      that OPAHs are formed in soils during microbial turnover of PAHs in a short time.

PMID- 24100049
TI  - Quantification of four artificial sweeteners in Finnish surface waters with
      isotope-dilution mass spectrometry.
AB  - The artificial sweeteners sucralose (SCL), acesulfame (ACS), saccharin (SAC), and
      cyclamate (CYC) have been detected in environmental waters in Europe and North
      America. Higher environmental levels are expected in view of the increasing
      consumption of these food additives. In this study, an isotope-dilution mass
      spectrometry (IDMS) LC-MS/MS method was developed and validated for quantifying
      the four artificial sweeteners in boreal lakes (n = 3) and rivers (n = 12). The
      highest concentrations of ACS, SAC, CYC and SCL were 9,600, 490, 210 and 1000
      ng/L, respectively. ACS and SAC were detected in all studied samples, and CYC and
      SCL in 98% and 56% of the samples. Seasonal trends of ACS and SAC were observed
      in some rivers. ACS and SCL concentrations in rivers correlated linearly with
      population equivalents of the wastewater treatment plants in the catchment areas,
      whereas SAC and CYC concentrations depend more on the source. 

PMID- 24100050
TI  - Effects of deltamethrin on excitability and contractility of the rainbow trout
      (Oncorhynchus mykiss) heart.
AB  - Pyrethroids are extensively used for the control of pest insects and disease
      vectors. Pyrethroid use is regarded safe due to their selective toxicity: they
      are effective against insects but relatively harmless to mammals and birds.
      Unfortunately, pyrethroids are very toxic to fishes. The high toxicity of
      pyrethroids to fishes is only partly explained by slow elimination rate of
      toxins, suggesting that high affinity binding to their molecular targets, the
      Na(+) channels, is involved. This study tests the hypothesis that Na(+) channels
      of the fish heart are targets to a type II pyrethroid, deltamethrin (DM), and
      therefore pyrethroids are cardiotoxic to fishes. In ventricular myocytes of the
      rainbow trout (Oncorhynchus mykiss) heart DM (10(-7)-3.10(-5) M) modified Na(+)
      current by slowing inactivation and shifting the reversal potential of the
      current to the left. Maximally 31+/-2% of the cardiac Na(+) channels were
      modified by DM and the half-maximal effect occurred at the concentration of 2.1
      MUM. The effect of DM on trout cardiac Na(+) channels is stronger and occurs
      about an order of magnitude lower in concentration in comparison to the
      orthologous mammalian Na(+) channels. In sinoatrial preparations of the trout
      heart DM (10 MUM) caused irregularities in rate, rhythm and force of the
      heartbeat indicating that DM can be arrhythmogenic for the trout heart.
      Consistent with this, DM (>0.1 MUM) induced spontaneous action potentials in
      otherwise quiescent ventricular myocytes. DM (10 MUM) did not affect calcium
      current or inward rectifier and delayed rectifier potassium currents.
      Collectively, these findings indicate that DM exerts cardiotoxic effects in
      trout, and suggest that the high sensitivity of fishes to pyrethroid toxicity
      might be partially due to the high affinity of fish Na(+) channels to
      pyrethroids.

PMID- 24100051
TI  - Exposure-dose-response of Tellina deltoidalis to metal contaminated estuarine
      sediments 2. Lead spiked sediments.
AB  - Lead accumulation in estuarine sediments, as a result of activities such as
      mining and ore smelting, and through urban runoff is a continuing problem in the
      increasingly developed world. Marine organisms accumulate lead, which is known to
      be highly toxic to biological processes and to degrade organism and ecosystem
      health. Here the relationship between lead exposure, dose and response was
      investigated in the sediment dwelling, deposit feeding, marine bivalve Tellina
      deltoidalis. Bivalves were exposed in the laboratory to individual lead spiked
      sediments at < 0.01, 100 and 300 MUg/g dry mass, for 28 days and accumulated
      total tissue lead concentrations of 4, 96 and 430 MUg/g, respectively.
      Subcellular fractionation indicated that around 70% of the total accumulated
      tissue lead was detoxified, three quarters of the detoxified lead fraction was
      converted into metal rich granules, with the remainder in the metallothionein
      like protein fraction. The majority of biologically active lead was associated
      with the mitochondrial fraction with up to a 128 fold increase in lead burden in
      exposed organisms compared to controls. This indicates lead detoxification was
      occurring but the organism was unable to prevent lead interacting with sensitive
      organelles. With increased lead exposure T. deltoidalis showed a suppression in
      glutathione peroxidase activity, total glutathione concentration and reduced
      GSH:GSSG ratios, however, these differences were not significant. Lead exposed T.
      deltoidalis had a significantly reduced total antioxidant capacity which
      corresponded with increased lipid peroxidation, lysosomal destabilisation and
      micronuclei frequency. The exposure-dose-response relationships demonstrated for
      lead exposed T. deltoidalis supports its potential for the development of
      sublethal endpoints in lead toxicity assessment.

PMID- 24100052
TI  - Identification and mRNA expression of antioxidant enzyme genes associated with
      the oxidative stress response in the Wuchang bream (Megalobrama amblycephala Yih)
      in response to acute nitrite exposure.
AB  - Aquatic organisms possess cellular detoxification systems to deal with
      pollutants. To explore the influence of reactive oxygen species (ROS) generated
      in response to nitrite on oxidative stress defenses and the antioxidant system in
      Megalobrama amblycephala, the full length cDNA sequences were determined for
      three antioxidant-related genes, namely catalase (MaCAT), selenium-dependent
      glutathione peroxidase (MaGPx1) and Cu/Zn superoxide dismutase (MaCu/Zn-SOD).
      Encoded polypeptides that exhibited high identity and similarity with
      corresponding proteins in other fish species. Expression levels of these
      antioxidant genes were analyzed by quantitative real-time polymerase chain
      reaction (qRT-PCR) technique. MaCAT, MaGPx1 and MaCu/Zn-SOD expression was
      greatest in the liver and qRT-PCR was used to assess expression of these genes in
      juvenile fish during 72 h of exposure to 15 mg/L nitrite. Prolonged nitrite
      exposure resulted in the formation of excess ROS that caused oxidative damage to
      lipids and proteins and reduced the activities of antioxidant enzymes. Fish
      exposed to nitrite also showed liver damage. This study provides transcriptional
      data for MaCAT, MaGPx1 and MaCu/Zn-SOD that suggest expression is related
      positively with oxidative stress induced by nitrite exposure, indicating that
      imbalance between ROS and antioxidant defenses is one mechanism underlying
      nitrite toxicity in M. amblycephala.

PMID- 24100053
TI  - Assessing the environmental health relevance of cooling towers--a systematic
      review of legionellosis outbreaks.
AB  - Bioaerosols from cooling towers are often suspected to cause community-acquired
      legionellosis outbreaks. Although Legionella infections can mostly be assigned to
      the emission sources, uncertainty exists about the release and distribution into
      the air, the occurrence of the respirable virulent form and the level of the
      infective concentration. Our study aimed to evaluate studies on legionellosis
      outbreaks attributed to cooling towers published within the last 11 years by
      means of a systematic review of the literature. 19 legionellosis outbreaks were
      identified affecting 12 countries. Recurring events were observed in Spain and
      Great Britain. In total, 1609 confirmed cases of legionellosis and a case
      fatality rate of approximately 6% were reported. Duration of outbreaks was 65
      days on average. For diagnosis the urinary antigen test was mainly used. Age,
      smoking, male sex and underlying diseases (diabetes, immunodeficiency) could be
      confirmed as risk factors. Smoking and underlying diseases were the most frequent
      risk factors associated with legionellosis in 11 and 10 of the 19 studies,
      respectively. The meteorological conditions varied strongly. Several studies
      reported a temporal association of outbreaks with inadequate maintenance of the
      cooling systems. A match of clinical and environmental isolates by serotyping
      and/or molecular subtyping could be confirmed in 84% of outbreaks. Legionella
      contaminated cooling towers as environmental trigger, in particular in the
      neighbourhood of susceptible individuals, can cause severe health problems and
      even death. To prevent and control Legionella contamination of cooling towers,
      maintenance actions should focus on low-emission cleaning procedures of cooling
      towers combined with control measurements of water and air samples. Procedures
      allowing rapid detection and risk assessment in the case of outbreaks are
      essential for adequate public health measures. Systematic registration of cooling
      towers will facilitate the identification of the source of outbreaks and help to
      shorten their duration. 

PMID- 24100054
TI  - Protection against chemotherapy-induced alopecia: targeting ATP-binding cassette
      transporters in the hair follicle?
AB  - Currently, efficacious treatments for chemotherapy-induced alopecia (hair loss)
      are lacking, and incidences of permanent hair loss following high-dose
      chemotherapy are on the increase. In this article, we describe mechanisms by
      which the pharmacological defense status of the hair follicle might be enhanced,
      thereby reducing the accumulation of cytotoxic cancer drugs and preventing or
      reducing hair loss and damage. We believe this could be achieved via the
      selective increase in ATP-binding cassette (ABC) transporter expression within
      the hair follicle epithelium, following application of topical agonists for
      regulatory nuclear receptors. Clinical application would require the development
      of hair follicle-targeted formulations, potentially utilizing nanoparticle
      technology. This novel approach has the potential to yield entirely new
      therapeutic options for the treatment and management of chemotherapy-induced
      alopecia, providing significant psychological and physical benefit to cancer
      patients. 

PMID- 24100055
TI  - Incidence of heparin-induced thrombocytopenia type II and postoperative recovery
      of platelet count in liver graft recipients: a retrospective cohort analysis.
AB  - BACKGROUND: Thrombocytopenia in patients with end-stage liver disease is a common
      disorder caused mainly by portal hypertension, low levels of thrombopoetin, and
      endotoxemia. The impact of immune-mediated heparin-induced thrombocytopenia type
      II (HIT type II) as a cause of thrombocytopenia after liver transplantation is
      not yet understood, with few literature citations reporting contradictory
      results. The aim of our study was to demonstrate the perioperative course of
      thrombocytopenia after liver transplantation and determine the occurrence of
      clinical HIT type II. METHOD: We retrospectively evaluated the medical records of
      205 consecutive adult patients who underwent full-size liver transplantation
      between January 2006 and December 2010 due to end-stage or malignant liver
      disease. Preoperative platelet count, postoperative course of platelets, and
      clinical signs of HIT type II were analyzed. RESULTS: A total of 155 (75.6%) of
      205 patients had thrombocytopenia before transplantation, significantly
      influenced by Model of End-Stage Liver Disease score and liver cirrhosis. The
      platelet count exceeded 100,000/MUL in most of the patients (n = 193) at a medium
      of 7 d. Regarding HIT II, there were four (1.95%) patients with a background of
      HIT type II. CONCLUSIONS: The incidence of HIT in patients with end-stage hepatic
      failure is, with about 1.95%, rare. For further reduction of HIT type II, the use
      of intravenous heparin should be avoided and the prophylactic anticoagulation
      should be performed with low-molecular-weight heparin after normalization of
      platelet count.

PMID- 24100056
TI  - The cross-cultural adaptation of the DASH questionnaire in Thai (DASH-TH).
AB  - STUDY DESIGN: Clinical measurement. INTRODUCTION: Currently there are no self
      report questionnaires in Thai to evaluate disability levels in patients suffering
      from upper extremity musculoskeletal disorders. PURPOSE OF THE STUDY: To
      translate and cross-cultural adaptation the disabilities of the arm, shoulder and
      hand (DASH) questionnaire to Thai version and to evaluate content validity,
      construct validity and internal consistency of the questionnaire. METHODS: The
      DASH-TH was produced by following cross-cultural adaptation guidelines stated by
      the Institute for Work and Health (IWH). Forty Thai patients with arm, shoulder
      or hand problems participated in field testing of the questionnaire. Content
      validity was determined by obtaining the item-objective congruence (IOC) value
      for each questionnaire item. Correlation between the DASH-TH score and numeric
      rating scale was used to assess construct validity. Internal consistency of DASH
      TH was measured using Cronbach's alpha coefficient. RESULTS: Forty patients (14
      males, 26 females) with arm, shoulder or hand problems enrolled in the present
      study. The average age of patients was 44.8 years. The index of item-objective
      congruence (IOC) of each item ranged from 0.7 to 1.0. The Cronbach's alpha
      coefficient of the questionnaire was 0.938. There was no correlation between DASH
      TH score and numeric rating scale. CONCLUSION: The DASH-TH has high content
      validity and internal consistency. LEVEL OF EVIDENCE: N/A.

PMID- 24100057
TI  - Avoiding common statistical pitfalls.

PMID- 24100058
TI  - Tumor feeding artery reconstruction with multislice spiral CT in the diagnosis of
      pelvic tumors of unknown origin.
AB  - PURPOSE: We aimed to compare multislice spiral computed tomography (MSCT)
      angiography diagnosis with both surgical findings and postoperative pathological
      results in patients with pelvic tumors of unknown origin. In addition, the
      diagnostic accuracy of MSCT angiography was compared with that of routine
      computed tomography for tumor feeding artery volume reconstruction to determine
      the origin and nature of pelvic tumors. MATERIALS AND METHODS: The records of 43
      patients with pelvic tumors of unknown origin who underwent MSCT angiography were
      retrospectively reviewed. Volume reconstructions using add vessel and merge views
      methods were performed for abdominal and pelvic blood vessels. The tumor origin
      was identified based on observations of the origin, number, morphology,
      starting/ending locations, route, and distribution of the tumor feeding arteries.
      RESULTS: Overall, the mean tumor diameter was 9.8+/-3.5 cm (range, 4.2-23.5 cm);
      11 tumors (25.6%) were cystic in nature; and 32 tumors (74.4%) were either
      solid/cystic or solid in nature. When considering all MSCT angiography
      examinations used to predict the nature of the tumor (e.g., malignant or benign),
      the sensitivity and specificity were 77.3% and 95.2%, respectively. The positive
      and negative predictive values were 94.4% and 80%, respectively. The overall
      diagnostic accuracy was 86.05% with an area under the curve of 0.961 (95%
      confidence interval, 0.913-1.000). CONCLUSIONS: MSCT angiography volume
      reconstruction for pelvic tumor feeding arteries of unknown origin is highly
      valuable for localization, qualitative diagnosis, and quantitative diagnosis of
      pelvic tumors.

PMID- 24100059
TI  - Clinical, pathological, and imaging characteristics of primitive neuroectodermal
      tumors of the spine.
AB  - Primitive neuroectodermal tumors (PNETs) located in the spine are extremely rare,
      and information concerning these tumors in the medical literature is limited to
      single case reports. This pictorial essay presents the clinical, pathological,
      and imaging characteristics of PNET of the spine. 

PMID- 24100060
TI  - Efficacy of CT in diagnosis of transudates and exudates in patients with pleural
      effusion.
AB  - PURPOSE: We aimed to evaluate the efficacy of multidetector computed tomography
      (CT) imaging in diagnosis of pleural exudates and transudates using attenuation
      values. MATERIALS AND METHODS: This retrospective study included 106 patients who
      were diagnosed with pleural effusion between January 2010 and June 2012. After
      the patients underwent chest CT, thoracentesis was performed in the first week.
      The attenuation values of the pleural effusions were measured in all patients.
      RESULTS: According to Light's criteria, 30 of 106 patients with pleural effusions
      had transudates, and the remaining patients had exudates. The Hounsfield unit
      (HU) value of the exudates (median, 12.5; range, 4-33) was significantly higher
      than that of the transudates (median, 5; range, 2-15) (P = 0.001). Additionally,
      when evaluated by disease subgroups, congestive heart failure and empyema were
      predictable in terms of median HU values of the pleural effusions with high and
      moderate sensitivity and specificity values (84.6% and 81.2%, respectively; 76.9%
      and 66.7%, respectively). Compared with other patients, the empyema patients had
      significantly more loculation and pleural thickening. CONCLUSION: CT attenuation
      values may be useful in differentiating exudates from transudates. Although there
      is an overlap in most effusions, exudate can be considered when the CT
      attenuation values are >15 HU. Because of overlapping HU values, close
      correlation with clinical findings is essential. Additional signs, such as fluid
      loculation and pleural thickness, should be considered and may provide further
      information for the differentiation.

PMID- 24100061
TI  - Evaluation of the postnatal development of the sternum and sternal variations
      using multidetector CT.
AB  - PURPOSE: We aimed to evaluate the postnatal development and the maturation of the
      sternum and sternal variations using multidetector computed tomography (MDCT).
      Additionally, we aimed to examine the roles of gender and age in sternal
      development. MATERIALS AND METHODS: Two hundred and fifty patients who underwent
      thorax MDCT examinations were evaluated for sternal development and variations.
      Coronal curved planar reconstruction and maximum intensity projection images were
      used to better assess the ossification centers in the manubrium and the body of
      the sternum. Multiplanar images were used to accurately measure the thickness and
      the sagittal dimension of the manubrium, the sagittal dimension of the body, and
      the total sagittal dimension of the sternum in the sagittal plane. RESULTS: No
      significant differences in the manubrium measurements were observed between the
      genders. The thickness and sagittal dimension of the manubrium, sagittal
      dimension of the body, and total sagittal dimension of the sternum in the
      sagittal plane were significantly different between the age groups. We evaluated
      the ossification centers; shape and developmental variations in the manubrium and
      body; direction, calcification, and termination of the xiphoid process;
      developmental variations in the xiphoid process; and manubriosternal and
      sternoxiphoidal fusion. Significant variations were observed from person to
      person. CONCLUSION: The anatomy and the developmental properties of the sternum
      should be well understood in cases of potential chest and sternum injuries and in
      several surgical procedures. Therefore, knowledge of the development and the
      maturation of the sternum, and sternal variations and anomalies is important. We
      suggest that the postnatal development and the morphogenesis of the sternum can
      be adequately assessed using MDCT.

PMID- 24100062
TI  - Pulmonary subsolid nodules: what radiologists need to know about the imaging
      features and management strategy.
AB  - Pulmonary subsolid nodules (SSNs) refer to pulmonary nodules with pure ground
      glass nodules and part-solid ground-glass nodules. SSNs are frequently
      encountered in the clinical setting, such as screening chest computed tomography
      (CT). The main concern regarding pulmonary SSNs, particularly when they are
      persistent, has been lung adenocarcinoma and its precursors. The CT
      manifestations of SSNs help radiologists and clinicians manage these lesions.
      However, the management plan for SSNs has not previously been standardized.
      Recently, the Fleischner Society published recommendations for the management of
      incidentally detected SSNs. The guidelines reflect the new lung adenocarcinoma
      classification system proposed by the International Association for the Study of
      Lung Cancer, American Thoracic Society, and European Respiratory Society
      (IASLC/ATS/ERS) and include six specific recommendations according to the nodule
      size, solid portion and multiplicity. This review aims to increase the
      understanding of SSNs and the imaging features of SSNs according to their
      histology, natural course, possible radiologic interventions, such as biopsy,
      localization prior to surgery, and current management. 

PMID- 24100063
TI  - Correlation of minimum apparent diffusion coefficient with maximum standardized
      uptake on fluorodeoxyglucose PET-CT in patients with rectal adenocarcinoma.
AB  - PURPOSE: The aim of this study was to retrospectively assess the correlation
      between minimum apparent diffusion coefficient (ADCmin) values obtained from
      diffusion-weighted magnetic resonance imaging (MRI) and maximum standardized
      uptake values (SUVmax) obtained from positron emission tomography-computed
      tomography (PET-CT) in rectal cancer. MATERIALS AND METHODS: Forty-one patients
      with pathologically confirmed rectal adenocarcinoma were included in this study.
      For preoperative staging, PET-CT and pelvic MRI with diffusion-weighted imaging
      were performed within one week (mean time interval, 3+/-1 day). For ADC
      measurements, the region of interest (ROI) was manually drawn along the border of
      each hyperintense tumor on b=1000 s/mm2 images. After repeating this procedure on
      each consecutive tumor-containing slice to cover the entire tumoral area, ROIs
      were copied to ADC maps. ADCmin was determined as the lowest ADC value among all
      ROIs in each tumor. For SUVmax measurements, whole-body images were assessed
      visually on transaxial, sagittal, and coronal images. ROIs were determined from
      the lesions observed on each slice, and SUVmax values were calculated
      automatically. The mean values of ADCmin and SUVmax were compared using
      Spearman's test. RESULTS: The mean ADCmin was 0.62+/-0.19*10-3 mm2/s (range,
      0.368-1.227*10-3 mm2/s), the mean SUVmax was 20.07+/-9.3 (range, 4.3-49.5). A
      significant negative correlation was found between ADCmin and SUVmax (r=-0.347; P
      = 0.026). CONCLUSION: There was a significant negative correlation between the
      ADCmin and SUVmax values in rectal adenocarcinomas.

PMID- 24100064
TI  - Positional therapy for sleep apnea: a promising behavioral therapeutic option
      still waiting for qualified studies.

PMID- 24100065
TI  - Detection of Papaya leaf distortion mosaic virus by reverse-transcription loop
      mediated isothermal amplification.
AB  - Papaya leaf distortion mosaic virus (PLDMV) can infect transgenic papaya
      resistant to a related pathogen, Papaya ringspot virus (PRSV), posing a
      substantial threat to papaya production in China. Current detection methods,
      however, are unable to be used for rapid detection in the field. Here, a reverse
      transcription loop-mediated isothermal amplification (RT-LAMP) assay was
      developed for the detection of PLDMV, using a set of four RT-LAMP primers
      designed based on the conserved sequence of PLDMV CP. The RT-LAMP method detected
      specifically PLDMV and was highly sensitive, with a detection limit of 1.32*10(
      6) MUg of total RNA per reaction. Indeed, the reaction was 10 times more
      sensitive than one-step RT-PCR, while also requiring significantly less time and
      equipment. The effectiveness of RT-LAMP and one-step RT-PCR in detecting the
      virus were compared using 90 field samples of non-transgenic papaya and 90 field
      samples of commercialized PRSV-resistant transgenic papaya from Hainan Island.
      None of the non-transgenic papaya tested positive for PLDMV using either method.
      In contrast, 19 of the commercialized PRSV-resistant transgenic papaya samples
      tested positive by RT-LAMP assay, and 6 of those tested negative by RT-PCR.
      Therefore, the PLDMV-specific RT-LAMP is a simple, rapid, sensitive, and cost
      effective tool in the field diagnosis and control of PLDMV.

PMID- 24100066
TI  - Development of a high-throughput human cytomegalovirus quantitative PCR cell
      based assay.
AB  - This report describes the development and optimization of a quantitative real
      time PCR assay for evaluating human cytomegalovirus (CMV) replication in vitro
      and susceptibility to antiviral drugs. This assay measures the level of
      intracellular CMV DNA in both 96- and 384-well microplate formats. Normalization
      of CMV levels using mitochondrial DNA enhanced the robustness of the assay and
      minimized variability. The assay throughput was further enhanced by eliminating
      several wash steps and by lysing the cells directly in the presence of cell
      culture media, both of which had no impact on the assay metrics. The assay was
      validated using several known CMV antiviral compounds. The CMV quantitative PCR
      (qPCR) assay represents a rapid, reliable and reproducible method that can be
      used with both CMV laboratory strains and clinical isolates. 

PMID- 24100067
TI  - Testis morphometry and kinetics of spermatogenesis in the feral pig (Sus scrofa).
AB  - The feral pig (Sus scrofa sp) also known as Monteiro pig, originated from a
      domestic pig breed that was introduced into Pantanal region in Brazil in the
      eighteenth century. Although the feral pig has commercial potential, there are
      few reports in the literature concerning the reproductive biology of this
      species. Therefore, the aim of this study was to further describe the feral pig
      testis parenchyma as well as characterize the stages of the seminiferous
      epithelium cycle by tubular morphology method, and to evaluate the number of
      differentiated spermatogonia generations in this species. Eight sexually mature
      feral pigs were analyzed. Fragments of testes were embedded in plastic resin and
      used to prepare slides for morphometrical studies. It was concluded that the
      feral pig has six generations of differentiated spermatogonials (A1, A2, A3, A4,
      In, B) and that the cellular composition in the eight stages of the seminiferous
      epithelium cycle of these animals were very similar to those reported in species
      of suidae and tayssuidae already studied.

PMID- 24100068
TI  - Progestin-impregnated intravaginal sponges for estrus induction and
      synchronization influences on goats vaginal flora and antimicrobial
      susceptibility.
AB  - The objective was to characterize vaginal bacteria, their antimicrobial
      sensitivity, and the incidence of vaginitis, in goats before and after insertion
      of intravaginal sponges containing progesterone. Sponges were inserted in 37
      Saanen goats and removed after 6, 9 or 12d (G6, G9 and G12). At sponge removal,
      all goats had clinical signs of vaginitis. Sampling was conducted just before
      sponge insertion and at 0, 24, 48, and 72 h after sponge removal. Vaginal
      secretions were subjected to standard bacteriological procedures, including
      isolation of bacteria, subculture, and determination of sensitivity to
      antimicrobials (gentamicin, cefalotin, tetracycline, ciprofloxacin, trimethoprim
      sulfamethoxazole, amoxicillin and clavulanic acid, penicillin G and cefoxitin).
      Ciprofloxacin, gentamicin, tetracycline and trimethoprim-sulfamethoxazole were
      the most effective for coliforms (100% sensitivity), whereas ciprofloxacin,
      gentamicin and tetracycline were the most effective for cocci (100, 98.6 and
      97.2% sensitivity, respectively). In contrast, the least effective antimicrobials
      were cefalotin for the coliforms, and penicillin for the cocci (37.5 and 64.4%
      sensitivity, respectively), regardless of duration of implant presence and
      interval from implant removal to sampling. In conclusion, insertion of
      intravaginal progestin-impregnated sponges induced clinical vaginitis in goats.
      Members of Staphylococcus genus were the most frequently recovered species of the
      vaginal samples cultured, and all isolates were resistant to several
      antimicrobials.

PMID- 24100069
TI  - In vivo effects of Trichostatin A - A histone deacetylase inhibitor - On
      chromatin remodeling during Triturus cristatus spermatogenesis.
AB  - A major challenge in developmental biology field is to decipher the molecular
      mechanisms involved in cellular differentiation and to understand the processes
      that control and regulate genes expression. The study of nuclear molecular
      architecture during gametogenesis represents one approach toward deciphering the
      molecular organization and function of the eukaryotic chromatin. As
      spermatogenesis progresses, there is a widespread reorganization of the haploid
      genome followed by extensive DNA compaction. It is becoming increasingly evident
      that the dynamic composition of chromatin plays an important role in the
      activities of enzymes and in the processes that act upon it. As the information
      in the existing literature regarding the epigenetic modifications occurring in
      the advanced stages of spermatogenesis of crested newt is still scarce, we have
      investigated the effect of a Histone Deacetylase (HDAC) inhibitor, Trichostatin A
      (TSA), at the cytological level (by transmission electron microscopy - TEM,
      immunohistochemistry technique, fluorescence microscopy) and at the molecular
      level (AUT-PAGE and ChIP assay) on Triturus cristatus spermatogenesis. Our
      results have revealed an important role for regulation of histone deacetylase
      activity in controlling histone hyperacetylation and the replacement with sperm
      nuclear basic proteins during spermiogenesis.

PMID- 24100070
TI  - The ductal origin of structural and functional heterogeneity between pancreatic
      islets.
AB  - Islets form in the pancreas after the first endocrine cells have arisen as either
      single cells or small cell clusters in the epithelial cords. These cords
      constitute the developing pancreas in one of its earliest recognizable stages.
      Islet formation begins at the time the cords transform into a branching ductal
      system, continues while the ductal system expands, and finally stops before the
      exocrine tissue of ducts and acini reaches its final expansion. Thus, islets
      continuously arise from founder cells located in the branching and ramifying
      ducts. Islets arising from proximal duct cells locate between the exocrine
      lobules, develop strong autonomic and sensory innervations, and pass their blood
      to efferent veins (insulo-venous efferent system). Islets arising from cells of
      more distal ducts locate within the exocrine lobules, respond to nerve impulses
      ending at neighbouring blood vessels, and pass their blood to the surrounding
      acini (insulo-acinar portal system). Consequently, the section of the ductal
      system from which an islet arises determines to a large extent its future
      neighbouring tissue, architecture, properties, and functions. We note that islets
      interlobular in position are frequently found in rodents (rats and mice), whereas
      intralobularly-located, peripheral duct islets prevail in humans and cattle.
      Also, we expound on bovine foetal Laguesse islets as a prominent foetal type of
      type 1 interlobular neuro-insular complexes, similar to neuro-insular
      associations frequently found in rodents. Finally, we consider the probable
      physiological and pathophysiological implications of the different islet
      positions within and between species. 

PMID- 24100074
TI  - An anterior ankle-foot orthosis improves walking economy in Charcot-Marie-Tooth
      type 1A patients.
AB  - BACKGROUND: Ankle-foot orthoses are commonly prescribed in Charcot-Marie-Tooth
      type 1A disease to improve quality of walking and reduce the risk of falling due
      to the foot drop. OBJECTIVES: This study aimed at assessing the effect of an
      anterior ankle-foot orthosis on walking economy in a group of Charcot-Marie-Tooth
      type 1A patients. STUDY DESIGN: Within-group comparisons. METHODS: 7 Charcot
      Marie-Tooth type 1A patients (four women and three men; 37 +/- 11 years; age
      range = 22-53 years) were asked to walk on a circuit at their self-selected
      speeds ('slow', 'comfortable' and 'fast') in two walking conditions: (1) with
      shoes only and (2) with Taloelast((r)) anterior elastic ankle-foot orthoses.
      Speed of walking and metabolic cost of walking energy cost per unit of distance
      were assessed at the three self-selected speeds of walking for both walking
      conditions. RESULTS: Speed of walking at the three self-selected speeds did not
      differ between shoes only and anterior elastic ankle-foot orthoses, whereas
      walking energy cost per unit of distance at comfortable speed was lower in
      patients using anterior elastic ankle-foot orthoses with respect to shoes only
      (2.39 +/- 0.22 vs 2.70 +/- 0.19 J kg(-1) m(-1); P < 0.05). CONCLUSIONS: In
      Charcot-Marie-Tooth type 1A patients, the use of anterior elastic ankle-foot
      orthoses improved walking economy by reducing the energy cost of walking per unit
      of distance, thus reflecting a lower level of metabolic effort and improved
      mechanical efficiency in comparison with shoes only. CLINICAL RELEVANCE: From a
      practical perspective, Charcot-Marie-Tooth type 1A patients with anterior elastic
      ankle-foot orthoses can walk for a longer duration with a lower level of physical
      effort. Improvements in walking economy due to ankle-foot orthoses are likely a
      consequence of the reduction in steppage gait.

PMID- 24100075
TI  - Spectral changes in spontaneous MEG activity across the lifespan.
AB  - OBJECTIVE: The aim of this study is to explore the spectral patterns of
      spontaneous magnetoencephalography (MEG) activity across the lifespan. APPROACH:
      Relative power (RP) in six frequency bands (delta, theta, alpha, beta-1, beta-2
      and gamma) was calculated in a sample of 220 healthy subjects with ages ranging
      from 7 to 84 years. MAIN RESULTS: A significant RP decrease in low-frequency
      bands (i.e. delta and theta) and a significant increase in high bands (mainly
      beta-1 and beta-2) were found from childhood to adolescence. This trend was
      observed until the sixth decade of life, though only slight changes were found.
      Additionally, healthy aging was characterized by a power increase in low
      frequency bands. Our results show that spectral changes across the lifespan may
      follow a quadratic relationship in delta, theta, alpha, beta-2 and gamma bands
      with peak ages being reached around the fifth or sixth decade of life.
      SIGNIFICANCE: Our findings provide original insights into the definition of the
      'normal' behavior of age-related MEG spectral patterns. Furthermore, our study
      can be useful for the forthcoming MEG research focused on the description of the
      abnormalities of different brain diseases in comparison to cognitive decline in
      normal aging.

PMID- 24100076
TI  - Altered apoplastic ascorbate redox state in tobacco plants via ascorbate oxidase
      overexpression results in delayed dark-induced senescence in detached leaves.
AB  - Ascorbate oxidase (AO) is an apoplastic enzyme that uses oxygen to catalyse the
      oxidation of ascorbate (AA) to dehydroascorbate (DHA) via the unstable radical
      monodehydroascorbate (MDHA). Here, we report that transgenic tobacco plants
      (Nicotiana tabacum L. cv. Xanthi) with an in vivo lowered apoplastic AA redox
      state through increased AO expression demonstrate signs of delayed dark-induced
      senescence compared with wild-type plants, as shown by chlorophyll loss assay. In
      situ localization of hydrogen peroxide (H2O2) suggests that, although transgenic
      plants have higher constitutive levels of H2O2 under normal growth conditions,
      imposed dark-induced senescence results in smaller induction levels of H2O2, an
      observation which correlates with increased antioxidant enzyme activities and an
      induction in the expression of AA recycling genes compared with that in wild-type
      plants. Our current findings, combined with previous studies which showed the
      contribution of AO in the regulation of AA redox state, suggest that the
      reduction in AA redox state in the leaf apoplast of these transgenic plants
      results in an increase in the endogenous levels of H2O2, which provides a form of
      'acquired tolerance' to oxidative stress imposed by dark-induced senescence. 

PMID- 24100077
TI  - Novel highly potent serotonin 5-HT7 receptor ligands: structural modifications to
      improve pharmacokinetic properties.
AB  - Here we report the synthesis, pharmacological and pharmacokinetic evaluation of a
      pilot set of compounds structurally related to the potent and selective 5-HT7
      ligand LP-211. Among the studied compounds, N-pyridin-3-ylmethyl-3-[4-[2-(4
      methoxyphenyl)phenyl]piperazin-1-yl]ethoxy]propanamide (4b) showed high affinity
      for 5-HT7 receptors (K(i)=23.8 nM), selectivity over 5-HT1A receptors (>50-fold),
      in vitro metabolic stability (82%) and weak interaction with P-glycoprotein
      (BA/AB=3.3). Compound 4b was injected ip in mice to preliminarily evaluate its
      distribution between blood and brain.

PMID- 24100078
TI  - Click chemistry based synthesis of dopamine D4 selective receptor ligands for the
      selection of potential PET tracers.
AB  - Taking advantage of click chemistry, a library of N-arylpiperazinylmethyl
      triazoles bearing fluoro substituted appendages was synthesized and the target
      compounds were investigated for dopamine and serotonin receptor binding. With the
      aim to bias their hydrophilicity and to optimize their D4 receptor affinity and
      selectivity, a concise series of triazoles containing fluoroalkyl, fluoroalkoxy,
      fluoroalkoxyphenyl, and deoxyfluoroglucosyl substituents was studied. The D4
      receptor affinity and selectivity could be tuned by altering the chemical moiety
      attached to the triazole unit. Among the test compounds, the fluoroethoxyphenyl
      derivative 15b showed weak partial agonism at D4 and a K(i) value of 14 nM, while
      its fluoropropoxyphenyl homologue 16a turned out to act as a neutral D4
      antagonist (K(i)=5.1 nM). Both, 15b and 16a revealed an excellent balance between
      D4 receptor affinity and subtype selectivity, providing lead candidates for the
      development of (18)F-labeled radioligands for D4 receptor imaging studies by
      positron emission tomography (PET).

PMID- 24100079
TI  - Maize centromeres expand and adopt a uniform size in the genetic background of
      oat.
AB  - Most existing centromeres may have originated as neocentromeres that activated de
      novo from noncentromeric regions. However, the evolutionary path from a
      neocentromere to a mature centromere has been elusive. Here we analyzed the
      centromeres of nine chromosomes that were transferred from maize into oat as the
      result of an inter-species cross. Centromere size and location were assayed by
      chromatin immunoprecipitation for the histone variant CENH3, which is a defining
      feature of functional centromeres. Two isolates of maize chromosome 3 proved to
      contain neocentromeres in the sense that they had moved from the original site,
      whereas the remaining seven centromeres (1, 2, 5, 6, 8, 9, and 10) were retained
      in the same area in both species. In all cases, the CENH3-binding domains were
      dramatically expanded to encompass a larger area in the oat background (~3.6 Mb)
      than the average centromere size in maize (~1.8 Mb). The expansion of maize
      centromeres appeared to be restricted by the transcription of genes located in
      regions flanking the original centromeres. These results provide evidence that
      (1) centromere size is regulated; (2) centromere sizes tend to be uniform within
      a species regardless of chromosome size or origin of the centromere; and (3)
      neocentromeres emerge and expand preferentially in gene-poor regions. Our results
      suggest that centromere size expansion may be a key factor in the survival of
      neocentric chromosomes in natural populations. 

PMID- 24100080
TI  - Offspring psychological and biological correlates of parental posttraumatic
      stress: review of the literature and research agenda.
AB  - Millions of individuals with posttraumatic stress disorder (PTSD) are parents. A
      burgeoning literature suggests that offspring of parents with this condition may
      be at increased risk for psychological problems. The current paper provides an
      integrative and comprehensive review of the diverse research literature examining
      the sequelae of parental posttraumatic stress among offspring. Over 100 studies
      that evaluated psychological and/or biological variables among children of
      parents with PTSD are reviewed. Findings suggest parental symptoms of
      posttraumatic stress are uniquely related to an array of offspring outcomes,
      including internalizing-type problems, general behavioral problems, and altered
      hypothalamic-pituitary-adrenal axis functioning. Although very little work has
      directly evaluated mechanisms of transmission, there is increasing support for
      genetic and epigenetic effects as well as parenting behaviors. These and other
      mechanisms are discussed; drawing upon findings from other literatures to
      consider how parental PTSD may impart psychobiological vulnerability upon
      offspring. We conclude with a detailed discussion of the methodological strengths
      and challenges of the extant research, along with a recommended agenda for future
      research in this important area of study. 

PMID- 24100081
TI  - Mechanisms of change in interpersonal therapy (IPT).
AB  - Although interpersonal therapy (IPT) has demonstrated efficacy for mood and other
      disorders, little is known about how IPT works. We present interpersonal change
      mechanisms that we hypothesize account for symptom change in IPT. Integrating
      relational theory and insights based on research findings regarding stress,
      social support, and illness, IPT highlights contextual factors thought to
      precipitate and maintain psychiatric disorders. It frames therapy around a
      central interpersonal problem in the patient's life, a current crisis or
      relational predicament that is disrupting social support and increasing
      interpersonal stress. By mobilizing and working collaboratively with the patient
      to resolve this problem, IPT seeks to activate several interpersonal change
      mechanisms. These include: 1) enhancing social support, 2) decreasing
      interpersonal stress, 3) facilitating emotional processing, and 4) improving
      interpersonal skills. We hope that articulating these mechanisms will help
      therapists to formulate cases and better maintain focus within an IPT framework.
      Here we propose interpersonal mechanisms that might explain how IPT's
      interpersonal focus leads to symptom change. Future work needs to specify and
      test candidate mediators in clinical trials. We anticipate that pursuing this
      more systematic strategy will lead to important refinements and improvements in
      IPT and enhance its application in a range of clinical populations. 

PMID- 24100082
TI  - Functional combination strategy for prioritization of human miRNA target.
AB  - MicroRNAs (miRNAs) are a class of non-coding RNAs known to play important
      regulatory roles through targets, which can affect human cell proliferation,
      differentiation, and metabolism. Overlaps between different miRNA target
      prediction algorithms (MTPAs) are small, which limit the understanding of miRNA's
      biological functions. However, the overlaps increase on functional levels, such
      as Gene Ontology (GO), Protein-Protein Interaction Network (PPIN) and pathways.
      Here, we performed prioritization on existing predicted target sets for each
      miRNA by considering all the possible combinations of 7 functional levels. After
      analyzing the results of both single and multiple functional levels, we found
      that functional combination strategies including pathways and GO performed better
      in the prioritization of human miRNA target. The combination which performed best
      was "Pathway+GO BP+GO MF+GO CC+Target+PPIN". For the prioritized result of this
      combination, the valid target had top ranking, and our method performed better
      than the MTPAs after comparison adopting the validated ranking levels. Top genes
      in ranking lists generated by this strategy were either validated by experiments
      or share same functions with the corresponding miRNA/its validated genes in
      disease related biological processes. 

PMID- 24100083
TI  - Comments to "a rational, non-radioactive strategy for the molecular diagnosis of
      congenital adrenal hyperplasia due to 21-hydroxylase deficiency".

PMID- 24100084
TI  - Lack of association between LXRalpha and LXRbeta gene polymorphisms and
      prevalence of metabolic syndrome: a case-control study of an Iranian population.
AB  - The metabolic syndrome (MetS) is considered to be a major risk factor for type 2
      diabetes mellitus and cardiovascular diseases. It is characterized by central
      adiposity, high blood pressure, glucose intolerance and abnormalities of
      lipoprotein metabolism. The cause of MetS is likely to be due to a complex
      interaction between genetic and environmental factors. Liver X receptors alpha
      (NR1H3) and beta (NR1H2) play a key role in lipid and carbohydrate metabolism.
      The aim of this study was to investigate the contribution of genetic
      polymorphisms in the LXRs to risk of MetS and related traits. Two common SNPs in
      NR1H3 (rs11039155 and rs2279238) and in NR1H2 (rs17373080 and rs2695121) were
      genotyped using TaqMan assays in MetS patients (n=265) and controls (n=219).
      Logistic regression analyses were performed to calculate the odds ratios (ORs) as
      a measure of association of genotypes with the presence of MetS and related
      phenotypes. Although The NR1H2 polymorphism rs2695121 was nominally associated
      with MetS but correction for multiple-testing and adjustment for age, sex and
      number of MetS criteria, failed to identify any significant interactions
      associated with prevalence of MetS. However in the haplotype analysis, a LXRalpha
      haplotype AC, was more common in controls and was associated with a significant
      protective effect for MetS (OR [95% CI]=0.25 [0.07-0.88], p=0.031). In
      conclusion, this study suggests that the above-named variants in LXRalpha and
      LXRbeta genes are not potential contributors to the risk of MetS and related
      traits in an Iranian population.

PMID- 24100085
TI  - Expression profiles of key transcription factors involved in lipid metabolism in
      Beijing-You chickens.
AB  - Intramuscular fat (IMF) is a crucial factor for the meat quality of chickens.
      With the aim of studying the molecular mechanisms underlying IMF deposition in
      chickens, the expression profiles of five candidate transcription factors
      involved in lipid metabolism in several tissues were examined in Beijing-You
      (BJY) chickens at five ages (0, 4, 8, 14 and 20 wk). Results showed that
      accumulation of IMF in breast (IMFbr), thigh (IMFth) and abdominal fat weight
      increased significantly (P<0.01) after 8 wk. Accumulation of both IMFbr and IMFth
      from 8 to 14 wk exceeded that from 14 to 20 wk; IMFth was 4-7 times of IMFbr. As
      for the expression profiles of key transcription factors: 1) expression of
      C/EBPalpha and PPARgamma in abdominal fat was significantly higher than that in
      breast and thigh muscles at all ages. The expression of C/EBPalpha was positively
      correlated with PPARgamma in both breast and thigh muscles, which indicated that
      both C/EBPalpha and PPARgamma promoted fat deposition and might act through a
      unified pathway; 2) the expression of SREBP-1 in 0, 4, and 8 wk in thigh muscle
      was significantly higher than that in breast; 3) expression of C/EBPbeta at 4 and
      8 wk was significantly higher than that at 14 and 20 wk; and it was positively
      correlated with IMFth and IMFbr from 0 to 8 wk; 4) expression of PPARalpha in
      breast and thigh muscles was significantly higher than that in abdominal fat.
      Taken together, all five transcription factors studied play roles in lipid
      metabolism in chickens with C/EBPalpha and PPARgamma being important effectors.

PMID- 24100086
TI  - Cloning and functional analysis of HpFAD2 and HpFAD3 genes encoding Delta12- and
      Delta15-fatty acid desaturases in Hansenula polymorpha.
AB  - Two fatty acid desaturase genes have been cloned: HpFAD2 and HpFAD3 encode
      Hansenula polymorpha Delta12-fatty acid desaturase (HpFad2) and Delta15-fatty
      acid desaturase (HpFad3), which are responsible for the production of linoleic
      acid (LA, C18:2, Delta9, Delta12) and alpha-linolenic acid (ALA, alphaC18:3,
      Delta9, Delta12, Delta15), respectively. The open reading frame of the HpFAD2 and
      HpFAD3 genes is 1215bp and 1239bp, encoding 405 and 413 amino acids,
      respectively. The putative amino acid sequences of HpFad2 and HpFad3 share more
      than 60% similarity and three conserved histidine-box motifs with other known
      yeast Fad homologs. Hpfad2Delta disruptant cannot produce C18:2 and alphaC18:3,
      while the deletion of HpFAD3 only causes the absence of alphaC18:3. Heterologous
      expression of either the HpFAD2 or the HpFAD3 gene in Saccharomyces cerevisiae
      resulted in the presence of C18:2 and alphaC18:3 when the C18:2 precursor was
      added. Taken together, these observations indicate that HpFAD2 and HpFAD3 indeed
      encode Delta12- and Delta15-fatty acid desaturases that function as the only ones
      responsible for desaturation of oleic acid (C18:1) and linoleic acid (C18:2),
      respectively, in H. polymorpha. Because a Fatty Acid Regulated (FAR) region and a
      Low Oxygen Response Element (LORE), which are responsible for regulation of a
      Delta9-fatty acid desaturase gene (ScOLE1) in S. cerevisiae, are present in the
      upstream regions of both genes, we investigated whether the transcriptional
      levels of HpFAD2 and HpFAD3 are affected by supplementation with nutrient
      unsaturated fatty acids or by low oxygen conditions. Whereas both genes were up
      regulated under low oxygen conditions, only HpFAD3 transcription was repressed by
      an excess of C18:1, C18:2 and C18:3, while the HpFAD2 transcript level did not
      significantly change. These observations indicate that HpFAD2 expression is not
      controlled at the transcriptional level by fatty acids even though it contains a
      FAR-like region. This study indicates that HpFAD2 may be regulated by post
      transcriptional mechanisms, whereas HpFAD3 may be mainly controlled at a
      transcriptional level.

PMID- 24100087
TI  - Polymorphisms of folate metabolism-related genes and survival of patients with
      colorectal cancer in the Korean population.
AB  - BACKGROUND: 5-Fluorouracil (5-FU) is a cornerstone of chemotherapy for colorectal
      cancer (CRC), and the major targets of 5-FU are thymidylate synthase (TS),
      methylenetetrahydrofolate reductase (MTHFR), and reduced folate carrier 1 (RFC1).
      We hypothesized that polymorphisms in the genes encoding these proteins would be
      associated with CRC patient survival. PATIENTS AND METHODS: We genotyped the
      following polymorphisms in 372 CRC patients: TS enhancer region (TSER), TS
      1494del6, MTHFR 677C>T and 1298A>C, and RFC1 -43T>C, 80G>A, and 696C>T. Using
      Kaplan-Meier curves, log-rank tests, and Cox proportional hazard models, we
      evaluated associations between these polymorphisms and overall survival (OS).
      RESULTS: The combined TS 1494 0bp6bp+6bp6bp genotype was associated with reduced
      OS compared to the TS 1494 0bp0bp genotype. Among rectal cancer patients, the
      RFC1 -43CC and 80AA genotypes were associated with favorable OS. CONCLUSIONS: Our
      data suggest that TS and RFC1 polymorphisms are associated with CRC prognosis in
      Korean patients. Further studies are needed to verify these findings.

PMID- 24100088
TI  - Efficient and simple generation of unmarked gene deletions in Mycobacterium
      smegmatis.
AB  - Genetic research in molecular laboratories relies heavily on directed mutagenesis
      and gene deletion techniques. In mycobacteria, however, genetic analysis is often
      hindered by difficulties in the preparation of deletion mutants. Indeed, in
      comparison to the allelic exchange systems available for the study of other
      common model organisms, such as Saccharomyces cerevisiae and Escherichia coli,
      mycobacterial gene disruption systems suffer from low mutant isolation success
      rates, mostly due to inefficient homologous recombination and a high degree of
      non-specific recombination. Here, we present a gene deletion system that combines
      efficient homologous recombination with advanced screening of mutants. This novel
      methodology allows for gene disruption in three consecutive steps. The first step
      relies on the use of phage Che9c recombineering proteins for directed insertion
      into the chromosome of a linear DNA fragment that encodes GFP and confers
      hygromycin resistance. In the second step, GFP positive and hygromycin resistant
      colonies are selected, and in the last step, the gfp-hyg cassette is excised from
      the chromosome, thus resulting in the formation of an unmarked deletion. We
      provide a detailed gene deletion methodology and demonstrate the use of this
      genetic system by deleting the prcSBA operon of Mycobacterium smegmatis. 

PMID- 24100089
TI  - A literature review on the mutual impact of the spousal caregiver-cancer patients
      dyads: 'communication', 'reciprocal influence', and 'caregiver-patient
      congruence'.
AB  - PURPOSE: A diagnosis of cancer is the start of a journey of distress and
      adjustment for both the patient and his/her spouse. However, the dyadic phenomena
      are less conceptualised and related research is in the early stages. This review
      explores concepts of mutuality among spousal caregiver-cancer patient dyads and
      identifies directions for future research. METHOD: A systematic search, including
      trawling through six electronic databases, a manual search, and an author search,
      was conducted to identity articles that had been published in English and Chinese
      from January 2000 to March 2013, using key terms related to caregiver-patients
      dyads in cancer care. An inductive content analysis approach was adopted to
      analyse and synthesise the concepts of spousal caregiver-cancer patient dyads.
      RESULTS: Thirty-one articles were identified. The findings are described
      according to Fletcher et al.'s proposals for conceptualising spousal caregiver
      patient dyads. The proposed concepts of 'communication', 'reciprocal influence',
      and 'caregiver-patient congruence' have been found to be interrelated, and to
      contribute to the spousal caregiver-patient dyads' mutual appraisal of caregiving
      and role adjustment through the cancer trajectory. CONCLUSIONS: The findings
      highlight the importance of a perspective that focuses on the nature of the
      relationship between couples coping with cancer and the quality of their
      communication with each other. It is recognised that communication may act as a
      fundamental element of the abovementioned three concepts. Better communication
      between couples would probably facilitate reciprocal influence and caregiver
      patient congruence, which in turn would have a positive effect on intimacy
      between the couple and improve the caregiving outcomes.

PMID- 24100090
TI  - Maintaining patency in totally implantable venous access devices (TIVAD): a time
      to-event analysis of different lock irrigation intervals.
AB  - PURPOSE: To evaluate the effectiveness of irrigating totally implantable venous
      access devices (TIVADs) every eight weeks instead of every four in maintaining
      the patency of the device. METHODS: An explorative, pragmatic, prospective study
      design was conducted in two day hospital centres located in the northeast of
      Italy, from January 2011 to September 2012. Twenty patients who had skipped an
      appointment and were thus washing their TIVAD every eight weeks (exposed) were
      included, as were 17 patients following the typical wash regimen of every four
      weeks (controls). TIVAD occlusion-defined as the inability of the device to
      aspirate blood and/or the inability to properly irrigate the device-was the
      principal study end-point. RESULTS: A total of six occlusions were documented in
      six patients. Four cases were observed among the exposed group (4/20; 20.0%),
      while two were observed among the control group (2/17; 11.7%). No statistically
      significant differences were observed in the occurrence of occlusion between the
      groups (RR: 1.29, 95%CI: 0.67-2.50, p = 0.49). No statistically significant
      differences emerged between groups in the time that elapsed from study inclusion
      to occlusion occurrence according to the time-to-event analysis performed using
      the Kaplan-Meier estimation model (Log Rank [Mantel-Cox] = chi(2) 0.284, df 1, p
      = 0.594). CONCLUSIONS: Within the limitations of the study which should be
      addressed with further research based on double-blinded randomised clinical
      trials, postponing the irrigation regimen of TIVADs to eight weeks seems to be
      sufficient to maintain device patency.

PMID- 24100091
TI  - A web-based tool to support shared decision making for people with a psychotic
      disorder: randomized controlled trial and process evaluation.
AB  - BACKGROUND: Mental health policy makers encourage the development of electronic
      decision aids to increase patient participation in medical decision making.
      Evidence is needed to determine whether these decision aids are helpful in
      clinical practice and whether they lead to increased patient involvement and
      better outcomes. OBJECTIVE: This study reports the outcome of a randomized
      controlled trial and process evaluation of a Web-based intervention to facilitate
      shared decision making for people with psychotic disorders. METHODS: The study
      was carried out in a Dutch mental health institution. Patients were recruited
      from 2 outpatient teams for patients with psychosis (N=250). Patients in the
      intervention condition (n=124) were provided an account to access a Web-based
      information and decision tool aimed to support patients in acquiring an overview
      of their needs and appropriate treatment options provided by their mental health
      care organization. Patients were given the opportunity to use the Web-based tool
      either on their own (at their home computer or at a computer of the service) or
      with the support of an assistant. Patients in the control group received care as
      usual (n=126). Half of the patients in the sample were patients experiencing a
      first episode of psychosis; the other half were patients with a chronic
      psychosis. Primary outcome was patient-perceived involvement in medical decision
      making, measured with the Combined Outcome Measure for Risk Communication and
      Treatment Decision-making Effectiveness (COMRADE). Process evaluation consisted
      of questionnaire-based surveys, open interviews, and researcher observation.
      RESULTS: In all, 73 patients completed the follow-up measurement and were
      included in the final analysis (response rate 29.2%). More than one-third
      (48/124, 38.7%) of the patients who were provided access to the Web-based
      decision aid used it, and most used its full functionality. No differences were
      found between the intervention and control conditions on perceived involvement in
      medical decision making (COMRADE satisfaction with communication: F1,68=0.422,
      P=.52; COMRADE confidence in decision: F1,67=0.086, P=.77). In addition, results
      of the process evaluation suggest that the intervention did not optimally fit in
      with routine practice of the participating teams. CONCLUSIONS: The development of
      electronic decision aids to facilitate shared medical decision making is
      encouraged and many people with a psychotic disorder can work with them. This
      holds for both first-episode patients and long-term care patients, although the
      latter group might need more assistance. However, results of this paper could not
      support the assumption that the use of electronic decision aids increases patient
      involvement in medical decision making. This may be because of weak
      implementation of the study protocol and a low response rate.

PMID- 24100092
TI  - Extraction agents for the removal of polycyclic aromatic hydrocarbons (PAHs) from
      soil in soil washing technologies.
AB  - Polycyclic aromatic hydrocarbons (PAHs) in soil have been recognised as a serious
      health and environmental issue due to their carcinogenic, mutagenic and
      teratogenic properties. One of the commonly employed soil remediation techniques
      to clean up such contamination is soil washing or solvent extraction. The main
      factor which governs the efficiency of this process is the solubility of PAHs in
      the extraction agent. Past field-scale soil washing treatments for PAH
      contaminated soil have mainly employed organic solvents or water which is either
      toxic and costly or inefficient in removing higher molecular weight PAHs. Thus,
      the present article aims to provide a review and discussion of the alternative
      extraction agents that have been studied, including surfactants, biosurfactants,
      microemulsions, natural surfactants, cyclodextrins, vegetable oil and solution
      with solid phase particles. These extraction agents have been found to remove
      PAHs from soil at percentages ranging from 47 to 100% for various PAHs. 

PMID- 24100093
TI  - Late left ventricular dysfunction after anatomic repair of congenitally corrected
      transposition of the great arteries.
AB  - OBJECTIVE: Early results for anatomic repair of congenitally corrected
      transposition of the great arteries (ccTGA) are excellent. However, the
      development of left ventricular dysfunction late after repair remains a concern.
      In this study we sought to determine factors leading to late left ventricular
      dysfunction and the impact of cardiac resynchronization as a primary and
      secondary (upgrade) mode of pacing. METHODS: From 1992 to 2012, 106 patients
      (median age at surgery, 1.2 years; range, 2 months to 43 years) with ccTGA had
      anatomic repair. A retrospective review of preoperative variables, surgical
      procedures, and postoperative outcomes was performed. RESULTS: In-hospital deaths
      occurred in 5.7% (n = 6), and there were 3 postdischarge deaths during a mean
      follow-up period of 5.2 years (range, 7 days to 18.2 years). Twelve patients
      (12%) developed moderate or severe left ventricular dysfunction. Thirty-eight
      patients (38%) were being paced at latest follow-up evaluation. Seventeen
      patients had resynchronization therapy, 9 as an upgrade from a prior dual-chamber
      system (8.5%) and 8 as a primary pacemaker (7.5%). Factors associated with left
      ventricular dysfunction were age at repair older than 10 years, weight greater
      than 20 kg, pacemaker implantation, and severe neo-aortic regurgitation. Eight of
      9 patients undergoing secondary cardiac resynchronization therapy (upgrade)
      improved left ventricular function. None of the 8 patients undergoing primary
      resynchronization developed left ventricular dysfunction. CONCLUSIONS: Late left
      ventricular dysfunction after anatomic repair of ccTGA is not uncommon, occurring
      most often in older patients and in those requiring pacing. Early anatomic repair
      and cardiac resynchronization therapy in patients requiring a pacemaker could
      preclude the development of left ventricular dysfunction.

PMID- 24100094
TI  - Risk factors for requiring extracorporeal membrane oxygenation support after a
      Norwood operation.
AB  - BACKGROUND: Patients requiring extracorporeal membrane oxygenation (ECMO) support
      after a Norwood operation constitute an extremely high-risk group. Data regarding
      risk factors for the requirement for ECMO post-Norwood are limited, however. We
      retrospectively assessed risk factors for requiring ECMO support after a Norwood
      operation during a 10-year period in a high-volume center. METHODS: Retrospective
      case-control study of 64 consecutive patients requiring ECMO support after a
      Norwood operation at a single institution during a 10-year period (January 2001
      December 2010), with a 3:1 era-matched control group of patients who underwent a
      Norwood but did not require ECMO. RESULTS: In univariate analysis, ascending
      aorta less than 2.0 mm, longer cardiopulmonary bypass (CPB) time, intraoperative
      shunt revision, and right ventricle to pulmonary artery conduit were associated
      with the need for postoperative ECMO. A single left ventricle was protective
      compared with single right ventricle anatomy. By multivariate logistic
      regression, birth weight less than 2.5 kg and longer CPB time were independently
      associated with the need for postoperative ECMO. Receiver-operating
      characteristic curve analysis identified a peak lactate of 9 mmol/L and a peak
      vasoactive inotrope score (VIS) of 27 within 48 hours of surgery as most
      prognostic of the need for ECMO. CONCLUSIONS: Birth weight less than 2.5 kg and
      longer CPB time are independently associated with the need for ECMO after a
      Norwood operation. Peak serum lactate and peak VIS may be useful in stratifying
      risk for ECMO. Risk factors for ECMO post-Norwood appear to be similar to the
      risk factors for early mortality post-Norwood.

PMID- 24100095
TI  - Mitral procedure selection in patients on dialysis: does mitral repair influence
      outcomes?
AB  - OBJECTIVE: To examine the likelihood of mitral valve repair among dialysis
      patients and the influence of mitral procedure selection on surgical outcomes in
      this cohort. METHODS: Among patients undergoing isolated primary mitral valve
      surgery in the Society of Thoracic Surgeons Adult Cardiac Surgery Database (2002
      2010), we used logistic regression models to evaluate the following: (1) the
      likelihood of attempted and successful mitral repair among dialysis patients
      (2008-2010), and (2) the impact of mitral procedural selection on surgical
      mortality and composite mortality/major morbidity experienced by dialysis
      patients (2002-2010). Patients with endocarditis and those undergoing emergent or
      major concomitant surgeries were excluded. RESULTS: The study cohort consisted of
      86,563 patients, of whom 1480 (1.7%) required preoperative dialysis. Dialysis
      patients had a high comorbid burden, including a high prevalence of congestive
      heart failure, stroke, diabetes, peripheral vascular disease, chronic obstructive
      pulmonary disease, and prior myocardial infarction. Dialysis-dependent patients
      had a lower propensity for mitral repair (44.6% vs 61.5%; P = .0010; adjusted
      odds ratio [OR], 0.69; 95% confidence interval [CI], 0.61-0.78); although the
      odds of successful repair (when attempted) were similar for dialysis versus
      nondialysis patients (OR, 0.87; 95% CI, 0.65-1.17). Compared with nondialysis
      patients, dialysis patients experienced a higher mortality rate (9.3% vs 2.3%; P
      < .0001; adjusted OR, 3.91; 95% CI, 3.17-4.81) and composite mortality or major
      morbidity (40.9% vs 15.9%; P < .0001; adjusted OR, 2.72; 95% CI, 2.41-3.07);
      however, adjustment for procedure selection did not substantially attenuate this
      effect (2.3% and 2.1% change-in-estimate for mortality and composite
      mortality/major morbidity, respectively). CONCLUSIONS: Dialysis patients undergo
      mitral repair less frequently, although repair success is equally likely when
      attempted among dialysis versus nondialysis patients. Dialysis-dependent renal
      failure is associated strongly with early mortality and major morbidity. However,
      procedure selection (repair vs replacement) does not appear to have a clinically
      meaningful impact on these short-term outcomes.

PMID- 24100096
TI  - Discussion.

PMID- 24100097
TI  - Understanding variability in hospital-specific costs of coronary artery bypass
      grafting represents an opportunity for standardizing care and improving resource
      use.
AB  - BACKGROUND: This study was undertaken to examine interhospital variability in
      inpatient costs of coronary artery bypass grafting (CABG). METHODS: The
      Nationwide Inpatient Sample was used to identify isolated CABGs performed between
      2005 and 2008 in the United States. Charges for inpatient care were supplied by
      the data set, and hospital charge-to-cost ratios were used to derive inpatient
      costs for each patient and aggregated at the hospital level. Mixed-effect linear
      regression models were created to evaluate variability in costs between hospitals
      adjusting for 34 patient, operative, complication, and hospital-related
      variables. RESULTS: A total of 633 hospitals performed isolated CABG in 183,973
      patients. In unadjusted analysis, there was significant baseline variability in
      average inpatient costs of CABG between hospitals (SD, $12,130; P < .001). This
      variability represented 30% of the overall unadjusted average cost of performing
      CABG per hospital ($40,424). After risk adjustment, significant variability in
      average costs between hospitals persisted (P < .001). Of the 34 additional
      variables included in the model, only hospital region, postoperative sepsis, in
      hospital mortality, and need for ventricular assist device, extracorporeal
      membrane oxygenation, permanent pacemaker, or implantable cardioverter
      defibrillator were stronger predictors of increased costs compared with the
      hospital effect. CONCLUSIONS: There is a wide variation in the cost of performing
      CABG in the United States. We determined that individual hospital centers,
      independent of multiple patient- and outcome-specific factors, are drivers of
      these differences. Comparison of hospital-specific behavior with identification
      of the causes of cost discrepancies represents an opportunity for standardization
      of care and improvement in resource use.

PMID- 24100098
TI  - Discussion.

PMID- 24100099
TI  - Incidence, dynamics, and prognostic value of acute kidney injury for death after
      cardiac surgery.
AB  - OBJECTIVE: This study relates long-term mortality after cardiac surgery to
      different methods of measuring postoperative renal function, classified according
      to the Risk, Injury, Failure, Loss, and End-stage (RIFLE) criteria. The dynamics
      of acute kidney injury during hospital stay were studied by comparing renal
      function preoperatively, at its poorest measurement, and at discharge. METHODS: A
      total of 5746 patients undergoing coronary artery bypass grafting were studied in
      a Cox analysis, over a median follow-up time of 6.0 years (range, 2.5-9.5 years).
      Renal function was determined using the highest and discharge levels of plasma
      creatinine by Cockroft-Gault and Modification of Diet in Renal Disease formulae.
      Acute kidney injury was classified according to the RIFLE criteria. Renal
      recovery was studied in a 2-dimensional matrix, and the impact of renal function
      at different time points was related to survival. RESULTS: Although the p
      creatinine classified most patients in the nonacute kidney injury and Risk class;
      the Cockroft-Gault and Modification of Diet in Renal Disease formulae classified
      more patients in Injury and Failure classes; and higher Risk, Injury, and Failure
      classes were associated with increased long-term mortality. The effect of renal
      recovery on long-term survival was only in part associated with improved outcome.
      In addition, the poorest renal function was a stronger predictor of mortality
      compared with preoperative and discharge levels. CONCLUSIONS: Classification
      using RIFLE criteria seems to be useful because it detects patients with renal
      impairment that affects long-term survival. The Modification of Diet in Renal
      Disease method seems to be the most robust method when predicting outcome, and
      the poorest renal function was the best predictor of outcome. Renal recovery was
      generally associated with better outcome.

PMID- 24100100
TI  - Off-pump transapical implantation of artificial chordae to correct mitral
      regurgitation: early results of a single-center experience.
AB  - OBJECTIVES: This study evaluated the safety and efficiency of the NeoChord DS1000
      system (NeoChord, Inc, Minneapolis, Minn), a device designed to deliver
      artificial chordae tendineae (neochords) in a beating heart with minimally
      invasive techniques through left anterolateral minithoracotomy. METHODS: Thirteen
      patients with severe mitral regurgitation and isolated posterior mitral valve
      leaflet prolapsed underwent operation with the NeoChord DS1000 system. Mitral
      valve dimensions were anteroposterior 34 mm (29-45 mm) and mediolateral 40 mm (29
      58 mm). All patients had an ejection fraction greater than 55%. With a beating
      heart, through a left anterolateral thoracotomy, under transesophageal
      echocardiographic guidance, the NeoChord DS1000 was introduced into the left
      ventricle 2 to 4 cm posterolateral from the apex. The prolapsed leaflet was
      grasped with the device, and expanded polytetrafluoroethylene suture deployed and
      attached to the posterior leaflet. Six patients received 2 sutures, 4 received 3
      sutures, and 2 received 4 sutures. All patients reached 6 months' follow-up and
      underwent transthoracic echocardiography to evaluate mitral regurgitation.
      RESULTS: Median operative duration was 113 minutes (80-150 minutes). Less than
      second-degree mitral regurgitation in 6 months was achieved in 11 patients (85%).
      One patient (8%) had recurrent mitral regurgitation in 1 month, and another had
      conversion to conventional mitral valve repair because of leaflet damage with the
      device. There were no further serious procedure-related complications.
      CONCLUSIONS: Beating-heart transapical neochord implantation was feasible, could
      be performed safely, and resulted in a relatively short procedure time. Larger
      studies and longer follow-up are needed to validate these promising results.

PMID- 24100101
TI  - Abnormal left ventricular diastolic function at late follow-up after repair of
      total anomalous pulmonary venous drainage: the impact of altered ventricular
      loading in utero.
AB  - BACKGROUND: Assessment of diastolic function has not been described after repair
      of total anomalous pulmonary venous drainage (TAPVD), but studies of exercise
      capacity demonstrate impaired performance in this population despite normal
      systolic function. We postulated that diastolic impairment might contribute to
      this finding. METHODS: We analyzed echocardiographic variables from 28 patients
      with repaired TAPVD and compared these with data from 32 healthy controls
      (normals) and 21 subjects with repaired transposition of the great arteries
      (TGA). RESULTS: Left ventricular (LV) end-diastolic volumes were smaller in the
      TAPVD group (median, 50 mL/m(2) compared with a median of 64 mL/m(2) in TGA and
      67 mL/m(2) in normals; P < .001 in each case). LV diastolic function in the TAPVD
      group was impaired. Mitral early to late ratio was increased (median, 2.7 in
      TAPVD compared with a median of 1.9 in TGA [P = .047] and 2.1 in normals [P =
      .021]). LV isovolumic relaxation time was reduced (median, 50 milliseconds in
      TAPVD compared with a median of 70 milliseconds in both TGA and normals; P < .001
      in each case). Late diastolic and systolic tissue Doppler velocities were lower
      and the E/e' ratio was higher in the TAPVD group. CONCLUSIONS: Patients with
      repaired TAPVD are usually regarded as having excellent outcomes, but the finding
      of LV diastolic dysfunction in this population warrants more careful follow-up.
      We postulate that the diastolic impairment in these patients is the result of
      relative unloading of the LV during early cardiac development. These findings may
      also have implications in considering therapeutic approaches for hypoplastic
      ventricles in attempting to achieve biventricular repair.

PMID- 24100102
TI  - Evaluation of different minimally invasive techniques in the surgical treatment
      of atrial septal defect.
AB  - OBJECTIVE: Minimally invasive cardiac surgery is becoming a safe and cosmetic
      alternative to standard median sternotomy (SMS). In the present retrospective
      study, we reviewed our results and experience with the totally thoracoscopic
      (TTS) and right vertical infra-axillary thoracotomy (RVIAT) techniques for atrial
      septal defect closure compared with SMS. METHODS: From December 2010 to February
      2012, 198 patients underwent repair of atrial septal defect using the TTS
      technique (n = 66), RVIAT (n = 59), or SMS (n = 73). Cardiopulmonary bypass was
      achieved peripherally in the TTS group and directly in the RVIAT and SMS groups.
      RESULTS: The procedures were performed successfully in all 3 groups, and no in
      hospital mortality occurred. No patient required conversion to SMS in the TTS
      group, although 2 patients did so in the RVIAT group. The cardiopulmonary bypass
      time was 87.26 +/- 21 minutes in the TTS group, 41.81 +/- 13.97 minutes in the
      RVIAT group, and 36.99 +/- 10.84 minutes in the SMS group (P < .01). The
      crossclamp time was 32.86 +/- 13.36, 22.54 +/- 9.08, and 19.23 +/- 6.92 minutes
      in the TTS, RVIAT, and SMS groups, respectively (P < .01). The total incision
      length in the SMS group (7.45 +/- 1.54 cm) was longer than that in the other
      groups (TTS group, 5.21 +/- 0.63 cm; RVIAT group, 6.48 +/- 1.37 cm); the
      difference was statistically significant (P < .01). CONCLUSIONS: The TTS
      technique and RVIAT can both be performed with favorable cosmetic and acceptable
      clinical results for closing atrial septal defects. They are promising
      alternatives to SMS and merit additional study.

PMID- 24100103
TI  - Discussion.

PMID- 24100104
TI  - The second best arterial graft: a propensity analysis of the radial artery versus
      the free right internal thoracic artery to bypass the circumflex coronary artery.
AB  - OBJECTIVE: We sought to determine if the radial artery (RA) or the free right
      internal thoracic artery (RITA) is the better conduit to bypass the circumflex
      coronary artery during coronary artery bypass grafting (CABG) using the left
      internal thoracic artery (LITA). METHODS: Propensity matching was performed on
      2488 CABG-LITA patients from 2 affiliated centers, resulting in 528 pairs who
      received either a RA at one center or a free RITA at the other center to bypass
      the circumflex coronary artery from 1995 to 2009. RESULTS: Kaplan Meier estimated
      1-, 5-, 10-, and 15-year survival rates were 99%, 95%, 85%, and 76% for RA
      patients, respectively, and 97%, 92%, 80%, and 71% for RITA patients,
      respectively (P = .060). Major adverse events (MAEs) were fewer in the RA group
      (7.6% vs 14.0%; P = .001) and use of the RA was a significant predictor of
      reduced MAEs (odds ratio [OR], 0.48; P = .002) in all patients and especially in
      diabetic (OR, 0.32; P = .003), older (OR, 0.40; P = .009), obese (OR, 0.15; P <
      .001), and chronic obstructive pulmonary disease (COPD) (OR, 0.05; P = .016)
      patients. However, survival was better with RA only in COPD (hazard ratio, 0.49;
      P = .045) and older (hazard ratio, 0.71; P = .050) patients. Overall RA patency
      (83.9%) was similar to RITA patency (87.4%) at a mean of 5.1 +/- 3.8 years (P =
      .155). CONCLUSIONS: Long-term survival is similar in CABG-LITA patients using
      either a RA or free RITA graft to bypass the circumflex coronary artery. RA
      grafting has fewer MAEs, a similar patency to RITA, and improves survival in
      older and COPD patients. The choice of the second arterial conduit should be
      guided by patient profiles and surgeon preferences.

PMID- 24100106
TI  - Continuous transformations of C60 crystals: polymorphs, polymers, and the ideal
      strength of fullerites.
AB  - Application of pressure is a versatile method to tailor the properties of organic
      semiconductors. For example, it is known that high pressure can transform C60
      face-centred-cubic (FCC) crystals to polymer structures with inter-molecular
      bonds. Here we use first-principles calculations to describe continuous
      crystalline transformation paths that include the FCC and polymer structures as
      distinct local energy minima. In addition to analysing the atomic-scale details
      of polymerization, we obtain the ideal strength of FCC-C60, identify metastable
      C60 crystalline polymorphs, and characterize their electronic properties-all key
      features for the performance of C60 crystals in organic electronic devices. 

PMID- 24100105
TI  - Right ventricular local longitudinal curvature as a marker and predictor for
      pulmonary valve replacement surgery outcome: an initial study based on
      preoperative and postoperative cardiac magnetic resonance data from patients with
      repaired tetralogy of Fallot.

PMID- 24100108
TI  - Pharyngo-occipital artery variant arising proximal to occluded internal carotid
      artery: the risk of an unnecessary endarterectomy.
AB  - Collateral branches originating from the cervical internal carotid artery (ICA)
      are rare but can have significant clinical and surgical implications. We present
      a case of pharyngo-occipital artery arising proximal from an occluded ICA that
      was missed and confused for severe stenosis of the ICA, leading to the misguided
      indication for carotid endarterectomy. Advanced preoperative studies allowed
      timely recognition of this anomaly and reconsideration of the therapeutic plan.
      We stress the importance of recognizing these variants by careful examination of
      multimodal pre-surgical exams. Awareness of these variants will allow a more
      precise diagnosis, and more appropriate management of patients with carotid
      artery disease. 

PMID- 24100107
TI  - Comparative physicochemical and biological characterization of NIST Interim
      Reference Material PM2.5 and SRM 1648 in human A549 and mouse RAW264.7 cells.
AB  - The epidemiological association between exposure to fine particulate matter
      (PM2.5) and adverse health effects is well-known. Here we report the size
      distribution, metals content, endotoxin content, and biological activity of
      National Institute of Standards and Technology (NIST) Interim Reference Material
      (RM) PM2.5. Biological activity was measured in vitro by effects on cell
      viability and the release of four inflammatory immune mediators, from human A549
      alveolar epithelial cells or murine RAW264.7 monocytes. A dose range covering
      three orders of magnitude (1-1000MUg/mL) was tested, and biological activity was
      compared to an existing Standard Reference Material (SRM) for urban PM (NIST SRM
      1648). Robust release of IL-8 and MCP-1 from A549 cells was observed in response
      to IRM PM2.5 exposures. Significant TNF-alpha, but not IL-6, secretion from
      RAW264.7 cells was observed in response to both IRM PM2.5 and SRM 1648 particle
      types. Cytokine or chemokine release at high doses often occurred in the presence
      of cytotoxicity, likely as a result of externalization of preformed mediator. Our
      results are consistent with a local cytotoxic and pro-inflammatory mechanism of
      response to exposure to inhaled ambient PM2.5 and reinforce the continued
      relevance of in vitro assays for mechanistic research in PM toxicology. Our study
      furthers the goal of developing reference samples of environmentally relevant
      particulate matter of various sizes that can be used for hypothesis testing by
      multiple investigators. 

PMID- 24100109
TI  - Meningioma associated with Gorlin's syndrome.
AB  - Gorlin's syndrome or naevoid basal cell carcinoma syndrome is a rare autosominal
      dominant condition characterised by a variety of congenital anomalies and various
      malignancies. The chief manifestations include multiple basal cell naevi,
      mandibular cysts, plantar and palmar pits, vertebral and rib abnormalities and
      intracranial calcifications. We report a patient with Gorlin's syndrome
      associated with meningioma treated at our institution. The clinical and
      radiological features together with the management strategies of this unusual
      disease entity are discussed. 

PMID- 24100110
TI  - Chemical meningitis: a rare presentation of Rathke's cleft cyst.
AB  - Rathke's cleft cysts (RCC) are usually benign, sellar and/or suprasellar lesions
      originating from the remnants of Rathke's pouch. Rarely, RCC can present with
      chemical meningitis, sellar abscess, lymphocytic hypophysitis, or intracystic
      hemorrhage. We describe an unusual presentation of RCC in which the patient
      presented with a clinical picture of chemical meningitis consisting of meningeal
      irritation, inflammatory cerebrospinal fluid profile, and enhancing pituitary and
      hypothalamic lesions, in addition to involvement of the optic tracts and optic
      nerve. 

PMID- 24100111
TI  - Bibrachial amyotrophy and ventral spinal cyst associated with myelomalacia and
      intracranial hypertension.
AB  - It has been recently recognised that patients with ventral intraspinal fluid
      collections secondary to cerebrospinal fluid leaks can present with bibrachial
      amyotrophy or mimic Hirayama disease. Here we present two further patients that
      expand the clinical spectrum of this disorder to include association with
      myelomalacia and intracranial hypertension. 

PMID- 24100112
TI  - Eradication of Helicobacter pylori after endoscopic resection of gastric tumors
      does not reduce incidence of metachronous gastric carcinoma.
AB  - BACKGROUND & AIMS: It is not clear whether eradication of Helicobacter pylori
      infection reduces the risk for metachronous gastric carcinoma. We performed a
      prospective, randomized, open-label trial of the effects of H pylori eradication
      on the incidence of metachronous carcinoma after endoscopic resection of gastric
      tumors. METHODS: From April 2005 through February 2011 there were 901 consecutive
      patients with H pylori infection who had been treated with endoscopic resection
      for gastric dysplasia or cancer and who were assigned randomly to groups given
      therapy to eradicate the infection (n = 444) or no therapy (controls, n = 457).
      The eradication group received 20 mg omeprazole, 1 g amoxicillin, and 500 mg
      clarithromycin twice daily for 1 week. Patients underwent endoscopic examination
      3, 6, and 12 months after treatment, and then yearly thereafter. The primary
      outcome was development of metachronous gastric carcinoma. RESULTS: During a
      median follow-up period of 3 years, 10 patients who received H pylori eradication
      and 17 controls developed metachronous carcinoma; this difference was not
      significant (P = .15). The incidence of metachronous carcinoma between the 2
      groups did not differ significantly at 1, 2, 3, and 4 years after administration
      of the therapy. There were no significant differences in the development of
      metachronous carcinoma among patients who were positive (n = 16) or negative (n =
      11) for H pylori infection (P = .32). CONCLUSIONS: In this prospective trial,
      eradication of H pylori after endoscopic resection of gastric tumors did not
      significantly reduce the incidence of metachronous gastric carcinoma.
      ClinicalTrials.gov Number: NCT01510730.

PMID- 24100113
TI  - High dietary glycemic load increases the risk of non-gallstone-related acute
      pancreatitis: a prospective cohort study.
AB  - BACKGROUND & AIMS: Obesity and type 2 diabetes--diseases linked to glucose
      intolerance and insulin resistance--have been positively associated with the risk
      of acute pancreatitis. However, it is unclear whether consumption of foods that
      increase postprandial glycemia and insulinemia have similar associations. We
      examined the association between dietary glycemic load and risk of non-gallstone
      related acute pancreatitis. METHODS: We performed a prospective study of 44,791
      men and 36,309 women (aged 45-84 years), without a history of acute pancreatitis,
      from the Cohort of Swedish Men and the Swedish Mammography Cohort. Glycemic loads
      were calculated from food frequency questionnaire data collected in 1997, and
      participants were followed for the development of non-gallstone-related acute
      pancreatitis through 2010 via linkage to the Swedish National Patient Register.
      Hazard ratios (HRs) were estimated using Cox proportional hazard models. RESULTS:
      During a total follow-up of 967,568 person-years, there were 364 cases of
      incident non-gallstone-related acute pancreatitis (236 in men and 128 in women).
      Incidence rates, standardized for age and sex, were 49 cases per 100,000 person
      years in the highest quartile of glycemic load and 33 cases per 100,000 person
      years in the lowest. The multivariate-adjusted HR of non-gallstone-related acute
      pancreatitis was 1.60 (95% confidence interval [CI], 1.17-2.18) for the highest
      compared with the lowest quartile. Every 50-unit increase in glycemic load per
      day (~ 3 servings of white bread) had an HR of 1.38 in men (95% CI, 1.11-1.72)
      and women (95% CI, 1.02-1.86). CONCLUSIONS: Based on a large, prospective cohort
      study, diets with high glycemic load are associated with an increased risk of non
      gallstone-related acute pancreatitis.

PMID- 24100114
TI  - Difficult mask ventilation: Tegaderm for sealing a patient's fate!

PMID- 24100115
TI  - Management of delayed hemorrhage after partial vocal cord cordectomy.
AB  - A patient developed brisk airway bleeding after being discharged earlier that day
      following an uneventful partial vocal cord cordectomy. This emergent complication
      required management by the team of anesthesiologists and otorhinolaryngologists.
      A plausible explanation for the occurrence of this complication was the presence
      of aberrant arterial blood supply in the area of the vocal cords where the
      surgery was performed. 

PMID- 24100116
TI  - The use of caffeine for the treatment of apnea of prematurity and bradycardia in
      a holoprosencephalic child with cleft lip and palate.

PMID- 24100117
TI  - Oxygen: needed for life. But do we need supplemental oxygen during transfer from
      the OR to the PACU?

PMID- 24100118
TI  - Pigmented villonodular synovitis of the temporomandibular joint: CT imaging
      findings.
AB  - OBJECTIVE: The purpose of this study was to determine the characteristic computed
      tomography (CT) findings of pigmented villonodular synovitis (PVNS) of the
      temporomandibular joint (TMJ). STUDY DESIGN: Eight subjects with PVNS were
      examined with both pre and post contrast CT scans. All lesions were
      histopathologically confirmed through surgery. CT appearances of the lesions were
      reviewed. RESULTS: Among the eight subjects, 8 (100%) demonstrated soft tissue
      mass and enhancement after contrast administration, 6 (75%) appeared as all or
      focal areas of noncontrast hyperdensity, 6 (75%) had widening of the joint
      spaces. Bony erosion of the mandibular condyles and articular surfaces were found
      in 7 (87.5%) and 6 (75%) subjects, respectively. CONCLUSIONS: Based on the CT
      findings, PVNS of the TMJ is characterized by hyperdensity soft tissue mass and
      further increase in density after contrast administration, bony destruction of
      the mandibular condyles and skull base, and intracranial extension.

PMID- 24100119
TI  - Behaviorally specific versus non-specific suppression of accumbens shell-mediated
      feeding by ipsilateral versus bilateral inhibition of the lateral hypothalamus.
AB  - The nucleus accumbens shell (AcbSh) and lateral hypothalamus (LH) are linked in
      the control of food intake. Pharmacological inhibition of the LH may block AcbSh
      elicited feeding, but the behavioral phenotype associated with this feeding
      suppression is unknown. To examine this phenotype, adult male Sprague-Dawley rats
      were implanted with three cannulas - one unilaterally in the AcbSh and two
      bilaterally in the LH - to allow for central drug injections. The AcbSh received
      injections of the AMPA receptor antagonist DNQX or the GABAA receptor agonist
      muscimol, while the LH received injections of the NMDA receptor antagonist D-AP5
      or muscimol. Eating, drinking, grooming, locomotion, quiescence, and sleeping
      behaviors were measured every minute for 60 min post-injection. From these
      observational data, feeding bout durations, feeding frequency, and latency to
      feed were determined. AcbSh muscimol or DNQX increased food intake by increasing
      feeding bout durations and frequency and decreasing latency to feed. D-AP5 or
      muscimol, injected into the LH bilaterally or ipsilateral to the AcbSh injection,
      reversed these AcbSh-mediated effects. Though bilateral LH D-AP5 or muscimol
      injections blocked feeding responses, they also hastened onset of sleep. In
      contrast, ipsilateral LH D-AP5 or muscimol injections suppressed AcbSh-mediated
      feeding behaviors without substantially altering sleeping or other behaviors.
      These results suggest bilateral LH inhibition via NMDA receptor blockade or GABAA
      receptor activation produces behavioral effects that might indirectly suppress
      feeding, but ipsilateral LH inhibition through these receptors suppresses AcbSh
      AMPA and GABAA receptor-mediated feeding specifically. This evidence strengthens
      the concept of a feeding-specific association between these regions.

PMID- 24100120
TI  - On the relationship between the execution, perception, and imagination of action.
AB  - Humans can perform, perceive, and imagine voluntary movement. Numerous
      investigations of these abilities have employed variants of goal-directed aiming
      tasks because the Fitts's law equation reliably captures the mathematical
      relationship between movement time (MT) and accuracy requirements. The emergence
      of Fitts's speed-accuracy relationship during movement execution, perception, and
      imagination has led to the suggestion that these processes rely on common neural
      codes. This common coding account is based on the notion that the neural codes
      used to generate an action are tightly bound to the codes that represent the
      perceptual consequences of that action. It is suggested that during action
      imagination and perception the bound codes are activated offline through an
      action simulation. The present study provided a comprehensive testing of this
      common coding hypothesis by examining the characteristics of the Fitts
      relationship in movement execution, perception, and imagination within the same
      individuals. Participants were required to imagine and perceive reciprocal aiming
      movements with varying accuracy requirements before and after actually executing
      the movements. Consistent with the common coding account, the Fitts relationship
      was observed in all conditions. Critically, the slopes of the regression lines
      across tasks were not different suggesting that the core of the speed-accuracy
      trade-off was consistent across conditions. In addition, it was found that
      incidental limb position variability scaled to the amplitude of imagined
      movements. This motor overflow suggests motor system activation during action
      imagination. Overall, the results support the hypothesis that action execution,
      perception, and imagination rely on a common coding system. 

PMID- 24100121
TI  - Aging 5 years in 5 minutes: the effect of taking a memory test on older adults'
      subjective age.
AB  - How old one feels-one's subjective age-has been shown to predict important
      psychological and health outcomes. The current studies examined the effect of
      taking a standard memory test on older adults' subjective age. Study 1 showed
      that older adults felt older after taking a standard neuropsychological screening
      test and participating in a free-recall experiment than they felt at baseline.
      Study 2 showed that the effect was selective to older adults: Younger adults'
      subjective age was not affected by participating in the memory experiment. Study
      3 showed that the subjective-aging effect was specific to memory, as taking a
      vocabulary test for a similar amount of time did not affect older adults'
      subjective age. Finally, Study 4 showed that simply expecting to take a memory
      test subjectively aged older adults. The results indicate that being in a memory
      testing context affects older adults' self-perception by making them feel older. 

PMID- 24100123
TI  - Growth factor receptor-bound protein 2 promotes autophagic removal of amyloid
      beta protein precursor intracellular domain overload in neuronal cells.
AB  - The ascertainment of elevated levels of amyloid-beta protein precursor
      intracellular domain (AICD) in Alzheimer's disease (AD) brains and the fact that
      it contributes to AD-like pathology has geared the search toward a new paradigm.
      While studying endogenous as well as overexpressed Grb2-AICD interaction in AD
      cell models, it was found that Grb2 co-localized to compartments along with AICD.
      We report now that these vesicles form in a clathrin and dynamin independent
      manner. Both types of vesicles mature into autophagosomes, merge with lysosomes,
      and relieve the cells of AICD overload. Inhibiting autophagosome formation
      results in vesicle accumulation. AICD-level is reduced in Grb2 excess condition
      in Cycloheximide Chase setup. Reduced caspase activity and apoptosis point toward
      the fact that the cytotoxic effect of AICD is alleviated by its sequestration in
      autolysosomes. Hence we state that the entrapping of AICD in Grb2 vesicles and
      its clearance via autophagosomes is a survival contrivance on the part of the
      cell. This study unravels, for the first time, the roles of Grb2 in autophagy and
      in handling toxic protein overload in an AD-like scenario. 

PMID- 24100122
TI  - Gene hunting in the genomic era: approaches to diagnostic dilemmas in patients
      with primary immunodeficiencies.
AB  - There are more than 180 different genetic causes of primary immunodeficiencies
      identified to date. Approaches for identifying causative mutations can be broadly
      classified into 3 strategies: (1) educated guesses based on known signaling
      pathways essential for immune cell development and function, (2) similarity of
      clinical phenotypes to mouse models, and (3) unbiased genetic approaches. Next
      generation DNA sequencing permits efficient sequencing of whole genomes or exomes
      but also requires strategies for filtering vast amounts of data. Recent studies
      have identified ways to solve difficult cases, such as diseases with autosomal
      dominant inheritance, incomplete penetrance, or mutations in noncoding regions.
      This review focuses on recently identified primary immunodeficiencies to
      illustrate the strategies, technologies, and potential pitfalls in finding novel
      causes of these diseases.

PMID- 24100124
TI  - Circadian misalignment and sleep disruption in mild cognitive impairment.
AB  - BACKGROUND: While it is evident that Alzheimer's disease is associated with
      disturbed sleep and circadian rhythms, the extent to which such changes are
      evident in older people 'at risk' of developing dementia is unknown. OBJECTIVE:
      In this study, we aimed to determine whether patients with mild cognitive
      impairment (MCI) demonstrated significant alterations in the timing of melatonin
      secretion onset and amount, as well as sleep architecture. METHODS: Thirty
      patients with MCI and 28 age-matched controls underwent psychiatric, medical, and
      neuropsychological assessment, followed by overnight polysomnography and dim
      light melatonin onset assessment. Participants also performed an episodic memory
      task while in the laboratory. Dim light melatonin onset was computed using a
      standardized algorithm, and area under the curve was computed for melatonin
      secretion. Sleep architecture measures including wake after sleep onset and
      latency to rapid eye movement sleep were derived. RESULTS: Patients with MCI had
      advanced timing of their melatonin secretion onset relative to controls, but the
      levels of melatonin secreted did not differ between groups. The MCI group also
      had greater wake after sleep onset and increased rapid eye movement sleep
      latency. There were differential associations between dim light melatonin onset
      and cognition between the two groups, with earlier dim light melatonin onset
      being associated with poorer memory performance in MCI patients. CONCLUSION:
      Circadian misalignment and sleep disruption is evident in patients with MCI, and
      is consistent with changes observed in Alzheimer's disease. Such findings could
      be a marker for disease trajectory, and may even be implicated in disease
      pathogenesis.

PMID- 24100125
TI  - Stroop effects in Alzheimer's disease: selective attention speed of processing,
      or color-naming? A meta-analysis.
AB  - Selective attention, an essential part of daily activity, is often impaired in
      people with Alzheimer's disease (AD). Usually, it is measured by the color-word
      Stroop test. However, there is no universal agreement whether performance on the
      Stroop task changes significantly in AD patients; or if so, whether an increase
      in Stroop effects reflects a decrease in selective attention, a slowing in
      generalized speed of processing (SOP), or is the result of degraded color-vision.
      The current study investigated the impact of AD on Stroop performance and its
      potential sources in a meta-analysis and mathematical modeling of 18 studies,
      comparing 637 AD patients with 977 healthy age-matched participants. We found a
      significant increase in Stroop effects for AD patients, across studies. This AD
      related change was associated with a slowing in SOP. However, after correcting
      for a bias in the distribution of latencies, SOP could only explain a moderate
      portion of the total variance (25%). Moreover, we found strong evidence for an AD
      related increase in the latency difference between naming the font-color and
      reading color-neutral stimuli (r2 = 0.98). This increase in the dimensional
      imbalance between color-naming and word-reading was found to explain a
      significant portion of the AD-related increase in Stroop effects (r2 = 0.87),
      hinting on a possible sensory source. In conclusion, our analysis highlights the
      importance of controlling for sensory degradation and SOP when testing cognitive
      performance and, specifically, selective attention in AD patients. We also
      suggest possible measures and tools to better test for selective attention in AD.

PMID- 24100126
TI  - Development of reduced kidney function in rheumatoid arthritis.
AB  - BACKGROUND: Rheumatoid arthritis (RA) is associated with a variety of kidney
      disorders. However, it is unclear whether the development of reduced kidney
      function is higher in patients with RA compared to the general population. STUDY
      DESIGN: Retrospective review. SETTING & PARTICIPANTS: Incident adult-onset RA
      cases (813) and a comparison cohort of non-RA individuals (813) in Olmsted
      County, MN, in 1980-2007. PREDICTOR: Baseline demographic and clinical variables.
      OUTCOMES: Reduced kidney function: (1) estimated glomerular filtration rate
      (eGFR)<60mL/min/1.73m(2) and (2) eGFR<45mL/min/1.73m(2) on 2 consecutive
      occasions at least 90 days apart; cardiovascular disease (CVD); and death.
      MEASUREMENTS: The cumulative incidence of reduced kidney function was estimated
      adjusting for the competing risk of death. RESULTS: Of 813 patients with RA and
      813 non-RA individuals, mean age was 56+/-16 (SD) years, 68% were women, and 9%
      had reduced kidney function at baseline. The 20-year cumulative incidence of
      reduced kidney function was higher in patients with RA compared with non-RA
      participants for eGFR < 60mL/min/1.73m(2) (25% vs 20%; P=0.03), but not
      eGFR<45mL/min/1.73m(2) (9% vs 10%; P=0.8). The presence of CVD at baseline (HR,
      1.77; 95% CI, 1.14-2.73; P=0.01) and elevated erythrocyte sedimentation rate in
      patients with RA (HR per 10-mm/h increase, 1.08; 95% CI, 1.00-1.16; P=0.04) was
      associated with increased risk of eGFR<60mL/min/1.73m(2). eGFR<60mL/min/1.73m(2)
      was not associated with increased risk of CVD development in patients with RA
      (HR, 0.99; 95% CI, 0.63-1.57; P=0.9), however, a greater reduction in GFR
      (eGFR<45mL/min/1.73m(2)) was associated with increased risk of CVD (HR, 1.93; CI,
      1.04-3.58; P=0.04). LIMITATIONS: Reduced kidney function was defined by
      estimating equations for kidney function. We are limited to deriving associations
      from our findings. CONCLUSIONS: Patients with RA were more likely to develop
      reduced kidney function over time. CVD and associated factors appear to play a
      role. The presence of RA in individuals with reduced kidney function may lead to
      an increase in morbidity from CVD development, for which awareness may provide a
      means for optimizing care.

PMID- 24100128
TI  - Treatment of hypomagnesemia.
AB  - Serum magnesium concentration is determined by the interplay of intestinal
      absorption and renal excretion. Hypomagnesemia can occur as a result of
      insufficient magnesium intake, increased gastrointestinal or renal loss, or
      redistribution from extracellular to intracellular compartments. A number of
      drugs are known to cause hypomagnesemia, including proton pump inhibitors (PPIs).
      We report the case of a patient with symptomatic hypomagnesemia due to short
      bowel syndrome and PPI therapy. Investigations revealed low 24-hour urinary
      magnesium excretion and secondary hypocalcemia. PPI treatment was withdrawn and
      the patient was managed with intravenous and oral magnesium and calcium
      replacement. This teaching case provides an evidence-based discussion of the
      treatment of hypomagnesemia. 

PMID- 24100129
TI  - Kidney disease in the setting of liver failure: core curriculum 2013.

PMID- 24100127
TI  - Comparison of associations of outcomes after stroke with estimated GFR using
      Chinese modifications of the MDRD study and CKD-EPI creatinine equations: results
      from the China National Stroke Registry.
AB  - BACKGROUND: The CKD-EPI (Chronic Kidney Disease Epidemiology Collaboration)
      creatinine equation estimates glomerular filtration rate (GFR) more precisely
      than the MDRD (Modification of Diet in Renal Disease) Study equation. The risk
      implications of this equation have been compared with the MDRD Study equation in
      different demographic and clinical characteristics. However, whether a Chinese
      modification of this equation performs better than a Chinese modification of the
      MDRD Study equation in risk prediction in Chinese patients with stroke is
      unknown. STUDY DESIGN: Prospective cohort study, China National Stroke Registry.
      SETTING & PARTICIPANTS: 15,791 consecutive patients with stroke enrolled from
      September 2007 to August 2008; follow-up time, 1 year. PREDICTOR: Estimated GFR
      (eGFR) and eGFR categories computed using Chinese modifications of the MDRD Study
      and CKD-EPI creatinine equations. OUTCOMES: All-cause mortality, recurrent
      stroke, stroke disability, combined end point of stroke or death. MEASUREMENTS:
      GFR was estimated by Chinese modifications of the MDRD Study (eGFRMDRD(CN)) and
      CKD-EPI (eGFRCKD-EPI(CN)) equations. RESULTS: The median value for eGFRCKD
      EPI(CN) was higher than that for eGFRMDRD(CN) (87.3 vs 82.5 mL/min/1.73 m(2);
      P<0.001). 22.8% of patients were reclassified by the CKD-EPI China equation
      (11.5% [1,818/15,791] to a higher eGFR category, and 11.3% [1,789/15,791], to a
      lower eGFR category). Of patients with eGFRMDRD(CN) of 60-89 and 30-59
      mL/min/1.73 m(2), 18.3% (1,299/7,090) and 18.4% (422/2,296) were reclassified
      upward to a higher eGFR category, respectively, reducing the CKD prevalence from
      16.4% to 14.2%. Net reclassification improvement favored the Chinese modification
      of the CKD-EPI equation for the prediction of all-cause mortality, stroke
      recurrence, death, or stroke recurrence and stroke disability (net
      reclassification improvements of 0.05, 0.03, 0.04, and 0.1, respectively; all
      P<0.01). LIMITATIONS: Relatively short follow-up time and no measurement of
      albuminuria. CONCLUSIONS: Our findings suggest that a Chinese modification of the
      CKD-EPI equation may improve risk prediction of all-cause mortality, stroke
      recurrence, death or stroke recurrence and stroke disability more than a Chinese
      modification of the MDRD Study equation in Chinese stroke patients.

PMID- 24100130
TI  - Mindfulness increases recall of self-threatening information.
AB  - Previous research has suggested that we tend to show impaired memory for self
      threatening information, an effect known as mnemic neglect. Mnemic neglect is
      believed to be due to shallow processing or inhibition of self-threatening
      information. Mnemic neglect, however, could also be an example of experiential
      avoidance and mindfulness training has been demonstrated to counteract
      experiential avoidance. The current study was designed to negate experiential
      avoidance on a memory task via mindfulness training and attempt to increase
      recall of self-threatening information. Participants were exposed to a short
      intervention, either mindfulness or unfocused attention, before being instructed
      to read and later recall self-referent behaviors. The findings indicated that
      recall of self-threatening and other self-referent information was increased
      following the mindfulness but not unfocused attention intervention. The utility
      of mindfulness as a strategy for negating the experiential avoidance normally
      associated with self-threatening information and increasing memory performance
      are discussed. 

PMID- 24100131
TI  - Two plus blue equals green: grapheme-color synesthesia allows cognitive access to
      numerical information via color.
AB  - In grapheme-color synesthesia, graphemes (e.g., numbers or letters) evoke color
      experiences. It is generally reported that the opposite is not true: colors will
      not generate experiences of graphemes or their associated information. However,
      recent research has provided evidence that colors can implicitly elicit symbolic
      representations of associated graphemes. Here, we examine if these
      representations can be cognitively accessed. Using a mathematical verification
      task replacing graphemes with color patches, we find that synesthetes can verify
      such problems with colors as accurately as with graphemes. Doing so, however,
      takes time: ~250 ms per color. Moreover, we find minimal reaction time switch
      costs for switching between computing with graphemes and colors. This
      demonstrates that given specific task demands, synesthetes can cognitively access
      numerical information elicited by physical colors, and they do so as accurately
      as with graphemes. We discuss these results in the context of possible cognitive
      strategies used to access the information.

PMID- 24100132
TI  - Effects of bone marrow mesenchymal stromal cells on gross motor function measure
      scores of children with cerebral palsy: a preliminary clinical study.
AB  - BACKGROUND AIMS: Pre-clinical evidence indicates that autologous bone marrow
      derived mesenchymal stromal cell (BM-MSC) transplantation improves motor function
      in patients with central nervous system disorders. METHODS: After providing
      informed consent, 52 patients with cerebral palsy (CP) who met the study criteria
      received BM-MSC transplantation. Gross motor function was assessed using the
      Gross Motor Function Measure (GMFM)-88 and GMFM-66 scales at baseline (before
      transplantation) and at 1 month, 6 months and 18 months post-transplantation. The
      participants completed the trial without visible side effects. The GMFM-66
      percentile (motor growth curves) was used as the control index of motor function
      to exclude the interference of improvement with age. RESULTS: The score domains
      A, B, C and D and the total GMFM-88 and GMFM-66 scores in participants increased
      at 1 month, 6 months and 18 months post-transplantation compared with the
      baseline value (P < 0.01). The scores of domain E also increased at 6 months and
      18 months post-transplantation, although they were not significantly increased at
      1 month post-transplantation. There were significant increases in the GMFM-66
      score and the GMFM-66 percentile corresponding to patient age and Gross Motor
      Function Classification System level after cell transplantation. CONCLUSIONS:
      Autologous BM-MSC transplantation appears to be a feasible, safe and effective
      therapy for patients with CP. The treatment improved the development of children
      with CP with regard to motor function.

PMID- 24100133
TI  - Evaluation of an in-clinic assay for the diagnosis of canine parvovirus.
AB  - The results of a study designed to evaluate the performance of an in-clinic test
      for the detection of canine parvovirus (CPV) are reported. A total of 150 faecal
      samples collected from dogs with acute diarrhoea were tested using the in-clinic
      test, a haemagglutination assay (HA) and a real-time PCR assay for CPV detection,
      quantification and characterisation. CPV was detected in 66, 73, and 101 faecal
      samples by in-clinic, HA and PCR testing, respectively. The relative sensitivity
      and specificity of the in-clinic test were 86.3% and 96.1%, respectively, when
      the test was compared to HA, and 65.3% and 100%, respectively, when compared to
      real-time PCR. The sample distribution according to the virus type was CPV-2a,
      n=44; CPV-2b, n=11; CPV-2c, n=44, CPV-2, n=2, as determined by minor groove
      binder probe assays and/or sequence analysis. The percentage of positive in
      clinic tests was 70.5% for CPV-2a, 72.7% for CPV-2b and 75.0% for CPV-2c
      (P>0.05). Using real-time PCR as the reference standard for CPV detection, the in
      clinic test was more specific than HA and had comparable sensitivity to HA,
      demonstrating detection rates similar to those previously observed for other
      rapid in-clinic tests. The in-clinic test was also able to detect all CPV types
      at equivalent rates. 

PMID- 24100134
TI  - Security concerns to be considered when downloading human immunodeficiency
      virus/sexually transmitted disease related smartphone applications.

PMID- 24100135
TI  - The X-ray crystal structure of APR-B, an atypical adenosine 5'-phosphosulfate
      reductase from Physcomitrella patens.
AB  - Sulfonucleotide reductases catalyse the first reductive step of sulfate
      assimilation. Their substrate specificities generally correlate with the
      requirement for a [Fe4S4] cluster, where adenosine 5'-phosphosulfate (APS)
      reductases possess a cluster and 3'-phosphoadenosine 5'-phosphosulfate reductases
      do not. The exception is the APR-B isoform of APS reductase from the moss
      Physcomitrella patens, which lacks a cluster. The crystal structure of APR-B, the
      first for a plant sulfonucleotide reductase, is consistent with a preference for
      APS. Structural conservation with bacterial APS reductase rules out a structural
      role for the cluster, but supports the contention that it enhances the activity
      of conventional APS reductases. 

PMID- 24100136
TI  - NMR localization of the O-mycoloylation on PorH, a channel forming peptide from
      Corynebacterium glutamicum.
AB  - PorH and PorA are two small peptides that, in complex, form a voltage-dependent
      ion channel in the outer membrane of Corynebacterium glutamicum. Specific post
      translational modifications on PorA and PorH are required for the formation of a
      functional ion channel. The assignment of PorH proton NMR chemical shifts in
      DMSO, allowed identifying unambiguously the exact position of the PorH O
      mycoloylation on Ser 56 side chain. This was further confirmed by site directed
      mutagenesis and mass spectrometry. Together with the previously published
      localization of PorA mycoloylation, this provides the complete primary structure
      characterization of this outer membrane porin. 

PMID- 24100137
TI  - Inhibitor selectivity between aldo-keto reductase superfamily members AKR1B10 and
      AKR1B1: role of Trp112 (Trp111).
AB  - The antineoplastic target aldo-keto reductase family member 1B10 (AKR1B10) and
      the critical polyol pathway enzyme aldose reductase (AKR1B1) share high
      structural similarity. Crystal structures reported here reveal a surprising
      Trp112 native conformation stabilized by a specific Gln114-centered hydrogen bond
      network in the AKR1B10 holoenzyme, and suggest that AKR1B1 inhibitors could
      retain their binding affinities toward AKR1B10 by inducing Trp112 flip to result
      in an "AKR1B1-like" active site in AKR1B10, while selective AKR1B10 inhibitors
      can take advantage of the broader active site of AKR1B10 provided by the native
      Trp112 side-chain orientation. 

PMID- 24100138
TI  - Functional and structural characterisation of a viral cytochrome b5.
AB  - Cytochrome b5 is a ubiquitous electron transport protein. The sequenced viral OtV
      2 genome, which infects Ostreococcus tauri, was predicted to encode a putative
      cytochrome b5 enzyme. Using purified OtV-2 cytochrome b5 we confirm this protein
      has identical spectral properties to purified human cytochrome b5 and
      additionally that the viral enzyme can substitute for yeast cytochrome b5 in
      yeast cytochrome P450 51 mediated sterol 14alpha-demethylation. The crystal
      structure of the OtV-2 cytochrome b5 enzyme reveals a single domain, comprising
      four beta sheets, four alpha helices and a haem moiety, which is similar to that
      found in larger eukaryotic cytochrome proteins. As a product of a horizontal gene
      transfer event involving a subdomain of the host fumarate reductase-like protein,
      OtV-2 cytochrome b5 appears to have diverged in function and is likely to have
      evolved an entirely new role for the virus during infection. Indeed, lacking a
      hydrophobic C-terminal anchor, OtV-2 encodes the first cytosolic cytochrome b5
      characterised. The lack of requirement for membrane attachment (in contrast to
      all other microsomal cytochrome b5s) may be a reflection of the small size of the
      host cell, further emphasizes the unique nature of this virus gene product and
      draws attention to the potential importance of cytochrome b5 metabolic activity
      at the extremes of cellular scale. 

PMID- 24100139
TI  - Activation of the yeast cell wall integrity MAPK pathway by zymolyase depends on
      protease and glucanase activities and requires the mucin-like protein Hkr1 but
      not Msb2.
AB  - Yeast adaptation to conditions in which cell wall integrity is compromised mainly
      relies on the cell wall integrity (CWI) mitogen-activated protein kinase (MAPK)
      pathway. Zymolyase, a mixture of cell wall-digesting enzymes, triggers a peculiar
      signaling mechanism in which activation of the CWI pathway is dependent on the
      high-osmolarity glycerol MAPK pathway. We have identified inhibitors of the
      principal enzyme activities present in zymolyase and tested their effect on the
      activation of the MAPK of the CWI pathway, Slt2/Mpk1. Eventually, only beta-1,3
      glucanase and protease activities were essential to elicit Slt2 activation and
      confer lytic power to zymolyase. Moreover, we show that the osmosensor Hkr1 is
      required for signaling, being the most upstream element identified to date. 

PMID- 24100141
TI  - The relationship between heart and 'inner self' from Aristotle to current
      clinical practice.
AB  - Modern songs, films, novels and daily speech often use heart imagery to
      illustrate 'inner self' experiences, such as deeply felt emotions. Where do these
      ideas come from and what relevance (if any) do they have for medicine today? This
      article explores some of the key origins and periods of development of
      heart/'inner self' ideas before considering the significance of heart/'inner
      self' interactions in modern clinical practice: from Aristotelian anatomy and the
      translated Hebrew Scriptures; through Shakespeare, William Harvey and the
      Protestant Reformation; to theories of emotion and modern-day cardiology. I
      conclude that heart/'inner self' interactions exist in clinically significant
      ways, but are poorly understood and under-recognised in healthcare settings.
      Greater integration of cardiovascular and psychosocial medicine would improve
      patient care. 

PMID- 24100140
TI  - Inhibition of ADP-ribosylation suppresses aberrant accumulation of lipidated
      apolipoprotein B in the endoplasmic reticulum.
AB  - ApoB-crescent, an endoplasmic reticulum (ER)-lipid droplet amalgamation
      structure, is a useful marker to indicate aberrant lipidated apolipoprotein B
      accumulation in the hepatocyte ER. Blockade of the ER-to-Golgi transport by
      either vesicle transport inhibitors or dominant-negative Arf1 caused a
      significant increase in ApoB-crescents. However, a low concentration of Brefeldin
      A induced the same result without affecting protein secretion, suggesting ADP
      ribosylation as an additional mechanism. ADP-ribosylation inhibitors not only
      suppressed the increase of ApoB-crescents, but also rapidly dissolved existing
      ApoB-crescents. These results implicate the involvement of ADP-ribosylation in
      the ApoB-crescent formation and maintenance process at the ER. 

PMID- 24100142
TI  - A comparison of the main structures of N-glycans of porcine islets with those
      from humans.
AB  - After producing alpha1-3-galactosyltransferase knockout (GKO) pigs, most of the
      organs of these pigs showed less antigenicity to the human body. However, wild
      type adult pig islets (API) that originally contained negligible levels of alpha
      galactosidase now showed a clear antigenicity to human serum. In this study, N
      glycans were isolated from both APIs and human islets. Their structures were then
      analyzed by a mapping technique based on their high-performance liquid
      chromatography elution positions and matrix-assisted laser desorption/ionization
      time-of-flight mass spectrometric data. Both preparations contained substantial
      amounts of high-mannose structures. The N-glycans from human islets were
      separated into 17 neutral, 8 mono-sialyl and 4 di-sialyl glycans, and the API
      glycans were comprised of 11 neutral, 8 mono-sialyl, 3 di-sialyl, 2 mono
      sulfated, 3 mono-sialyl-mono-sulfated and 1 di-sulfated glycans. Among them, the
      API preparation contained one neutral, five mono-sialyl glycans and six sulfated
      glycans that were not detected in human islets. The structures of 9 of these 12
      could be clearly determined. In addition, a study of the sulfate-depleted API
      suggests that sulfate residues could be antigenic to humans. The data herein will
      be helpful for future studies of the antigenicity associated with API. 

PMID- 24100143
TI  - Enhanced reduction of graphene oxide by means of charging and electric fields
      applied to hydroxyl groups.
AB  - We present a first-principles study of the effects of charging and perpendicular
      electric fields on hydroxyl groups, both of which mediate the reduction of
      graphene oxide through the formation of H2O and H2O2. Starting with an
      investigation of the interaction between the hydroxyl groups and graphene, we
      determine the equilibrium binding geometry, binding energy, and the diffusion
      path with a minimum energy barrier and show that those equilibrium properties are
      strongly affected by external agents. While co-adsorbed H and O form bound OH, co
      adsorbed H and OH in close proximity form H2O with almost no energy barrier. When
      negatively charged or subjected to a perpendicular electric field, the energy
      barrier between two OH co-adsorbed in close proximity is weakened or totally
      suppressed, forming an oxygen atom strongly bound at the bridge site, together
      with a water molecule. The water molecule by itself is very weakly bound to
      graphene and is prone to desorb from the surface, leading to the reduction of
      graphene oxide. It is therefore demonstrated that the reduction of graphene oxide
      is promoted to a large extent by negative charging or an applied perpendicular
      electric field, through the formation of weakly bound water molecules from
      hydroxyl groups. 

PMID- 24100144
TI  - Resolution by unassisted Top3 points to template switch recombination
      intermediates during DNA replication.
AB  - The evolutionarily conserved Sgs1/Top3/Rmi1 (STR) complex plays vital roles in
      DNA replication and repair. One crucial activity of the complex is dissolution of
      toxic X-shaped recombination intermediates that accumulate during replication of
      damaged DNA. However, despite several years of study the nature of these X-shaped
      molecules remains debated. Here we use genetic approaches and two-dimensional gel
      electrophoresis of genomic DNA to show that Top3, unassisted by Sgs1 and Rmi1,
      has modest capacities to provide resistance to MMS and to resolve recombination
      dependent X-shaped molecules. The X-shaped molecules have structural properties
      consistent with hemicatenane-related template switch recombination intermediates
      (Rec-Xs) but not Holliday junction (HJ) intermediates. Consistent with these
      findings, we demonstrate that purified Top3 can resolve a synthetic Rec-X but not
      a synthetic double HJ in vitro. We also find that unassisted Top3 does not affect
      crossing over during double strand break repair, which is known to involve double
      HJ intermediates, confirming that unassisted Top3 activities are restricted to
      substrates that are distinct from HJs. These data help illuminate the nature of
      the X-shaped molecules that accumulate during replication of damaged DNA
      templates, and also clarify the roles played by Top3 and the STR complex as a
      whole during the resolution of replication-associated recombination
      intermediates. 

PMID- 24100145
TI  - Characterization of SHP-1 protein tyrosine phosphatase transcripts, protein
      isoforms and phosphatase activity in epithelial cancer cells.
AB  - We identified 7 SHP-1 (PTPN6) transcripts using epithelial cancer-derived cell
      lines. Four were shown to utilize the epithelial promoter 1 to transcribe a full
      length, a partial (exon 3) or complete (exons 3 & 4) deletion of the N-SH2
      domain, and also a non-coding transcript having a stop codon caused by a frame
      shift due to intron 2 retention. Three additional transcripts were shown to
      utilize the hematopoietic promoter 2 to transcribe a full-length, a partial (exon
      3) deletion of the N-SH2 domain and a non-coding transcript with intron 2
      retention. We show that endogenous proteins corresponding to the open-reading
      frame (ORF) transcripts are produced. Using GST-fusion proteins we show that each
      product of the ORF SHP-1 transcripts has phosphatase activity and isoforms with
      an N-SH2 deletion have increased phosphatase activity and novel protein-protein
      interactions. This study is the first to document utilization of promoter 2 by
      SHP-1 transcripts and a noncoding transcript in human epithelial cells. 

PMID- 24100146
TI  - Laparoscopy in the morbidly obese: physiologic considerations and surgical
      techniques to optimize success.
AB  - The objectives of this review were to analyze the literature describing the
      benefits of minimally invasive gynecologic surgery in obese women, to examine the
      physiologic considerations associated with obesity, and to describe surgical
      techniques that will enable surgeons to perform laparoscopy and robotic surgery
      successfully in obese patients. The Medline database was reviewed for all
      articles published in the English language between 1993 and 2013 containing the
      search terms "gynecologic laparoscopy" "laparoscopy," "minimally invasive surgery
      and obesity," "obesity," and "robotic surgery." The incidence of obesity is
      increasing in the United States, and in particular morbid obesity in women.
      Obesity is associated with a wide range of comorbid conditions that may affect
      perioperative outcomes including hypertension, atherosclerosis, angina,
      obstructive sleep apnea, and diabetes mellitus. In obese patients, laparoscopy or
      robotic surgery, compared with laparotomy, is associated with a shorter hospital
      stay, less postoperative pain, and fewer wound complications. Specific intra
      abdominal access and trocar positioning techniques, as well as anesthetic
      maneuvers, improve the likelihood of success of laparoscopy in women with central
      adiposity. Performing gynecologic laparoscopy in the morbidly obese is no longer
      rare. Increases in the heaviest weight categories involve changes in clinical
      practice patterns. With comprehensive and thoughtful preoperative and surgical
      planning, minimally invasive gynecologic surgery may be performed safely and is
      of particular benefit in obese patients. 

PMID- 24100147
TI  - Adaptive plan selection vs. re-optimisation in radiotherapy for bladder cancer: a
      dose accumulation comparison.
AB  - PURPOSE: Patients with urinary bladder cancer are obvious candidates for adaptive
      radiotherapy (ART) due to large inter-fractional variation in bladder volumes. In
      this study we have compared the normal tissue sparing potential of two ART
      strategies: daily plan selection (PlanSelect) and daily plan re-optimisation
      (ReOpt). MATERIALS AND METHODS: Seven patients with bladder cancer were included
      in the study. For the PlanSelect strategy, a patient-specific library of three
      plans was generated, and the most suitable plan based on the pre-treatment cone
      beam CT (CBCT) was selected. For the daily ReOpt strategy, plans were re
      optimised based on the CBCT from each daily fraction. Bladder contours were
      propagated to the CBCT scan using deformable image registration (DIR).
      Accumulated dose distributions for the ART strategies as well as the non-adaptive
      RT were calculated. RESULTS: A considerable sparing of normal tissue was achieved
      with both ART approaches, with ReOpt being the superior technique. Compared to
      non-adaptive RT, the volume receiving more than 57 Gy (corresponding to 95% of
      the prescribed dose) was reduced to 66% (range 48-100%) for PlanSelect and to 41%
      (range 33-50%) for ReOpt. CONCLUSION: This study demonstrated a considerable
      normal tissue sparing potential of ART for bladder irradiation, with clearly
      superior results by daily adaptive re-optimisation.

PMID- 24100148
TI  - A comparison of the gamma index analysis in various commercial IMRT/VMAT QA
      systems.
AB  - PURPOSE: To investigate the variability of the global gamma index (gamma)
      analysis in various commercial IMRT/VMAT QA systems and to assess the impact of
      measurement with low resolution detector arrays on gamma. MATERIALS: Five
      commercial QA systems (PTW 2D-Array, Scandidos Delta4, SunNuclear ArcCHECK,
      Varian EPID, and Gafchromic EBT2 film) were investigated. The response of gamma
      analysis to deliberately introduced errors in pelvis and head & neck IMRT and
      RapidArcTM plans was evaluated in each system. A theoretical gamma was calculated
      in each commercial QA system software (PTW Verisoft, Delta4 software, SNC
      Patient, Varian Portal Dosimetry and IBA OmniPro, respectively), using treatment
      planning system resolution virtual measurements and compared to an independent
      calculation. Error-induced plans were measured on a linear accelerator and were
      evaluated against the error-free dose distribution calculated using Varian
      EclipseTM in the relevant phantom CT scan. In all cases, global gamma was used
      with a 20% threshold relative to a point selected in a high dose and low gradient
      region. The gamma based on measurement was compared against the theoretical to
      evaluate the response of each system. RESULTS: There was statistically good
      agreement between the predicted gamma based on the virtual measurements from each
      software (concordance correlation coefficient, rhoc>0.92) relative to the
      independent prediction in all cases. For the actual measured data, the agreement
      with the predicted gamma reduces with tightening passing criteria and the
      variability between the different systems increases. This indicates that the
      detector array configuration and resolution have greater impact on the
      experimental calculation of gamma due to under-sampling of the dose distribution,
      blurring effects, noise, or a combination. CONCLUSIONS: It is important to
      understand the response and limitations of the gamma index analysis combined with
      the equipment in use. For the same pass-rate criteria, different devices and
      software combinations exhibit varying levels of agreement with the predicted
      gamma analysis.

PMID- 24100149
TI  - Modern post-operative radiotherapy for stage III non-small cell lung cancer may
      improve local control and survival: a meta-analysis.
AB  - BACKGROUND: We hypothesized that modern postoperative radiotherapy (PORT) could
      decrease local recurrence (LR) and improve overall survival (OS) in patients with
      stage IIIA-N2 non-small-cell lung cancer (NSCLC). METHODS: To investigate the
      effect of modern PORT on LR and OS, we identified published phase III trials for
      PORT and stratified them according to use or non-use of linear accelerators. Non
      individual patient data were used to model the potential benefit of modern PORT
      in stage IIIA-N2 NSCLC treated with induction chemotherapy and resection.
      RESULTS: Of the PORT phase III studies, eleven trials (2387 patients) were
      included for OS analysis and eight (1677 patients) for LR. PORT decreased LR,
      whether given with cobalt, cobalt and linear accelerators, or with linear
      accelerators only. An increase in OS was only seen when PORT was given with
      linear accelerators, along with the most significant effect on LR (relative risk
      for LR and OS 0.31 (p=0.01) and 0.76 (p=0.02) for PORT vs. controls,
      respectively). Four trials (357 patients) were suitable to assess LR rates in
      stage III NSCLC treated with surgery, in most cases after induction chemotherapy.
      LR as first relapse was 30% (105/357) after 5 years. In the modeling part, PORT
      with linear accelerators was estimated to reduce LR rates to 10% as first relapse
      and to increase the absolute 5-year OS by 13%. CONCLUSIONS: This modeling study
      generates the hypothesis that modern PORT may increase both LR and OS in stage
      IIIA-N2 NSCLC even in patients being treated with induction chemotherapy and
      surgery.

PMID- 24100150
TI  - Dosimetric predictors of biochemical control of prostate cancer in patients
      randomised to external beam radiotherapy with a boost of high dose rate
      brachytherapy.
AB  - BACKGROUND: To correlate dose and volume dosimetric parameters (D90 and V100)
      with biochemical control in advanced prostate cancer treated with high-dose rate
      brachytherapy (HDR-BT). METHODS: One hundred and eight patients received external
      beam radiotherapy (EBRT) to 35.75 Gy in 13 fractions followed by HDR-BT of 2 *
      8.5 Gy. Kaplan-Meier freedom-from-biochemical relapse (FFbR; nadir+2 MUg/L) fits
      were grouped by the first (Q1), second (Q2) and third (Q3) D90 and V100
      quartiles. Groups were compared with the log-rank test. Univariate and
      multivariate Hazard Ratios (HR) for D90 and V100 and other co-variates (PSA,
      androgen deprivation therapy (ADT) were obtained using Cox's proportional hazard
      model. RESULTS: FFbR was significantly higher in patients whose D90 and V100 were
      at or above the second and third quartile (log rank p <= 0.04). In multivariate
      analysis D90, V100 were significant covariates for risk of relapse. CONCLUSIONS:
      Dichotomising the data using 6 levels of response (above and below Q1, Q2 and Q3)
      showed a progressive and continuous improvement in biochemical control of disease
      across the entire dose (and volume) range. The data show that a minimum D90 of
      108% of the prescribed dose should be the target to achieve.

PMID- 24100151
TI  - Microscopic disease extensions as a risk factor for loco-regional recurrence of
      NSCLC after SBRT.
AB  - PURPOSE: Stereotactic body radiotherapy (SBRT) is a highly conformal technique
      that allows a more accurate irradiation of lung tumors. However, a highly
      conformal dose distribution may underdose undetected microscopic disease
      extensions (MDE) near the tumor leading to loco-regional failure in tumor
      control. The purpose of the current work is to assess the risk of loco-regional
      failure in SBRT by analyzing pre-treatment scans. METHODS AND MATERIALS: A model
      to predict the risk of occurrence of MDE from pretreatment images was developed
      based on pathology samples of 47 lung cancer patients. This model was used to
      assess the outcome of 238 SBRT treatments. RESULTS: Patients with high risk of
      MDE presence showed significantly lower 2-year loco-regional control (82.0% vs.
      91.8%) and shorter time to loco-regional failure (8.4 months vs. 20.7 months)
      than low risk patients. The minimum dose delivered in the volume surrounding the
      GTV affected the model predictive power. The model remained predictive for
      patients who received less than 31 Gy in that volume. For patients who received
      larger doses, the MDE risk classification was not significant. CONCLUSIONS: The
      results show that MDEs are, at least partially, responsible of loco-regional
      failure in highly conformal radiotherapy. This information could be used to
      optimize dose distributions.

PMID- 24100152
TI  - Estimation of intracranial failure risk following hippocampal-sparing whole brain
      radiotherapy.
AB  - PURPOSE: To estimate the risk of undertreatment in hippocampal-sparing whole
      brain radiotherapy (HS-WBRT). METHODS: Eight hundred and fifty six metastases
      were contoured together with the hippocampi in cranial MRIs of 100 patients. For
      each metastasis, the distance to the closest hippocampus was calculated.
      Treatment plans for 10 patients were calculated and linear dose profiles were
      established. For SCLC and NSCLC, dose-response curves were created based on data
      from studies on prophylactic cranial irradiation, allowing estimating the risk
      for intracranial failure. RESULTS: Only 0.4% of metastases were located inside a
      hippocampus in 3% of all patients. SCLC showed a relatively high rate of
      hippocampal metastasis (18.2% of all SCLC patients) and HS-WBRT in a commonly
      applied fractionation scheme would increase the risk for brain relapse by ~4%
      compared to conventional WBRT. NSCLC showed a lower rate of brain metastasis in
      the hippocampi (2.8%) and HS-WBRT would account for a slightly increased absolute
      risk of 0.2%. CONCLUSIONS: Prophylactic or therapeutic HS-WBRT is expected to be
      associated with a low risk of undertreatment. For SCLC, it bears a minimally
      elevated risk of failure compared to standard WBRT. In NSCLC, HS-WBRT is most
      likely not associated with a clinically relevant increase in risk of failure.

PMID- 24100153
TI  - Comparative study between lag screw and miniplate fixation for straight midline
      mandibular osteotomy.
AB  - The mandibular swing approach is a surgical approach for the resection of
      malignant lesions localized in the posterior oral cavity and oropharynx. We
      analyzed 15 years of experience with fixation of the straight midline
      mandibulotomy and compared two fixation methods: lag screws and miniplates. A
      total of 117 patients underwent a straight midline mandibulotomy during the study
      period; 85 had fixation with two lag screws and 32 with two miniplates. The
      overall complication rate was low and there was no significant difference in
      complication rate regarding the fixation method (9% for miniplates vs. 7% for lag
      screws). The most serious complication over the whole study period was non union,
      which occurred in only two patients, followed by orocutaneous fistula and
      infection. Radiotherapy did not cause serious complications and is not regarded
      as hazardous in midline mandibulotomy patients. We conclude that lag screw
      fixation is at least as safe as miniplate fixation, but because of better
      fragment compression, offers faster bone healing. 

PMID- 24100154
TI  - Optimization of the interface between radiology, surgery, radiotherapy, and
      pathology in head and neck tumor surgery: a navigation-assisted multidisciplinary
      network.
AB  - A navigation-assisted multidisciplinary network to improve the interface between
      radiology, surgery, radiotherapy, and pathology in the field of head and neck
      cancer is described. All implicated fields are integrated by a common server
      platform and have remote data access in a ready-to-use format. The margins of
      resection and exact locations of biopsies are mapped intraoperatively. The
      pathologist uses the numerical coordinates of these samples to precisely trace
      each specimen in the anatomical field. Subsequently, map-guided radiotherapy is
      planned. In addition to the benefits of image-guided resection, this model
      enables radiotherapy planning according to the specific coordinates of the
      resection defect plus any residually affected sites identified by the
      pathologist. Irradiation of adjacent healthy structures is thereby minimized. In
      summary, the navigation-assisted network described grants timely
      multidisciplinary feedback between all fields involved, attains meticulous
      pathological definition, and permits optimized coordinate-directed radiotherapy. 

PMID- 24100155
TI  - Management of temporomandibular joint ankylosis type III: lateral arthroplasty as
      a treatment of choice.
AB  - Many surgical techniques for the management of temporomandibular joint (TMJ)
      ankylosis have been described in the literature. The purpose of this study was to
      report our experience using a lateral arthroplasty technique in the management of
      type III ankylosis. The records of 15 patients treated for TMJ ankylosis at our
      institution between 2007 and 2011 were reviewed. Pre- and postoperative
      information collected included age, gender, aetiology, ankylosis
      type/classification, existing facial asymmetry, maximum pre- and postoperative
      mouth opening, complications, and recurrence of ankylosis. The mean maximum inter
      incisal opening in the preoperative period was 12.9 mm and in the postoperative
      period was 36.2mm. No major complication was observed in any patient. No
      recurrence was noted in any patient. Our working hypothesis was that for patients
      with ankylosis type III, the medially displaced condyle and disc can fulfil their
      role in mandibular function and growth after extirpation of the ankylozed mass.
      Although they are located in an awkward medial position, they should function
      exactly as they would after a properly treated, displaced condylar fracture.

PMID- 24100156
TI  - Synthetic trimethyllysine receptors that bind histone 3, trimethyllysine 27
      (H3K27me3) and disrupt its interaction with the epigenetic reader protein CBX7.
AB  - Post-translational modifications act as 'on' or 'off' switches causing downstream
      changes in gene transcription. Modifications such as trimethylation of lysine 27
      on histone H3 (H3K27me3) cause repression of transcription and stable gene
      silencing, and its presence is associated with aggressive cancers of many types.
      We report here macrocyclic host-type compounds that can bind H3K27me3
      preferentially over unmethylated H3K27, and characterize their binding affinities
      and selectivities using a convenient dye-displacement method. We also show that
      they can disrupt the protein-protein interaction of H3K27me3 with the chromobox
      homolog 7 (CBX7), a methyllysine reader protein, using fluorescence polarization.
      These results show that sub-micromolar potencies are achievable with this family
      of host compounds, and suggest the possibility of their use as new tools to
      induce the disruption of methyllysine-mediated protein-protein interactions and
      to report on lysine methylation in vitro. 

PMID- 24100157
TI  - Actions of the Klenow fragment of DNA polymerase I and some DNA glycosylases on
      chemically stable analogues of N7-methyl-2'-deoxyguanosine.
AB  - N7-methyl-9-deaza-dG was synthesized and incorporated into oligonucleotides.
      Thermal melting studies showed that replacement of dG by N7-methyl-9-deaza-dG
      only slightly decreased DNA duplex stability. Replication of DNA templates
      containing N7-methyl-9-deaza-dG and the related 7-methyl-7-deaza-dG and 7-deaza
      dG by the Klenow fragment of Escherichia coli DNA polymerase I was examined. The
      dNTP misinsertion frequencies on all three templates were comparably low,
      although the 7-methyl group significantly slowed down the turnover rates of the
      polymerase when dCTP was incorporated. The stabilities of N7-methyl-9-deaza-dG
      and 7-methyl-7-deaza-dG against the actions of formamidopyrimidine DNA
      glycosylase (Fpg) and human alkyladenine DNA glycosylase (hAAG) were also
      examined. N7-methyl-9-deaza-dG was stable in the presence of both enzymes. In
      contrast, 7-methyl-7-deaza-dG was cleaved by Fpg, and possibly by hAAG but at an
      extremely slow rate. This study suggests that N7-alkyl-9-deaza-dG is a better
      analogue than 7-alkyl-7-deaza-dG for cellular studies. 

PMID- 24100158
TI  - Discovery of NMS-E973 as novel, selective and potent inhibitor of heat shock
      protein 90 (Hsp90).
AB  - Novel small molecule inhibitors of heat shock protein 90 (Hsp90) were discovered
      with the help of a fragment based drug discovery approach (FBDD) and subsequent
      optimization with a combination of structure guided design, parallel synthesis
      and application of medicinal chemistry principles. These efforts led to the
      identification of compound 18 (NMS-E973), which displayed significant efficacy in
      a human ovarian A2780 xenograft tumor model, with a mechanism of action confirmed
      in vivo by typical modulation of known Hsp90 client proteins, and with a
      favorable pharmacokinetic and safety profile. 

PMID- 24100159
TI  - DNA loop domain organization as revealed by single-cell gel electrophoresis.
AB  - At higher order levels chromatin is organized into loops. This looping, which
      plays an important role in transcription regulation and other processes, remains
      poorly understood. We investigated the kinetics of DNA loop migration during
      single cell gel electrophoresis (the comet assay). The migration of a part of the
      loops was shown to be reversible after switching off electrophoresis and to be
      sensitive to intercalation-induced changes in supercoiling. Another group of the
      loops migrates rapidly, the rate being insensitive to the supercoiling level. The
      largest part of the loops cannot migrate at all, presumably because of their
      large size. The loop ends can be detached in the presence of high concentrations
      of intercalators or protein denaturants, thus increasing the fraction of DNA that
      cannot migrate in the gel. The distribution of the loop length up to 100kilobases
      appears to be consistent with the fractal globule organization. 

PMID- 24100160
TI  - Dexamethasone increases alphavbeta3 integrin expression and affinity through a
      calcineurin/NFAT pathway.
AB  - The purpose of this study was to determine how dexamethasone (DEX) regulates the
      expression and activity of alphavbeta3 integrin. FACS analysis showed that DEX
      treatment induced expression of an activated alphavbeta3 integrin. Its expression
      remained high as long as DEX was present and continued following DEX removal.
      FACS analysis showed that the upregulation of alphavbeta3 integrin was the result
      of an increase in the expression of the beta3 integrin subunit. By real time
      qPCR, DEX treatment induced a 6.2-fold increase (p<0.04) in beta3 integrin mRNA
      by day 2 compared to control and remained elevated for 6days of treatment and
      then an additional 10days once the DEX was removed. The increase in beta3
      integrin mRNA levels required only 1day of DEX treatment to increase levels for
      4days in the absence of DEX. In contrast, DEX did not alter beta1 integrin mRNA
      or protein levels. The DEX-induced upregulation of beta3 integrin mRNA was partly
      due to an increase in its half-life to 60.7h from 22.5h in control cultures
      (p<0.05) and could be inhibited by RU486 and cycloheximide, suggesting that DEX
      induced de novo protein synthesis of an activation factor was needed. The
      calcineurin inhibitors cyclosporin A (CsA) and FK506 inhibited the DEX induced
      increase in beta3 integrin mRNA. In summary, the DEX-induced increase in beta3
      integrin is a secondary glucocorticoid response that results in prolonged
      expression of alphavbeta3 integrin and the upregulation of the beta3 integrin
      subunit through the calcineurin/NFAT pathway. 

PMID- 24100161
TI  - Metabolic remodeling in frataxin-deficient yeast is mediated by Cth2 and Adr1.
AB  - Frataxin is a mitochondrial protein involved in iron metabolism whose deficiency
      in humans causes Friedreich ataxia. We performed transcriptomic and proteomic
      analyses of conditional Yeast Frataxin Homologue (Yfh1) mutants (tetO7-YFH1) to
      investigate metabolic remodeling upon Yfh1 depletion. These studies revealed that
      Yfh1 depletion leads to downregulation of many glucose-repressed genes. Most of
      them were Adr1 targets, a key transcription factor required for growth in non
      fermentable carbon sources. Using a GFP-tagged Adr1, we observed that Yfh1
      depletion promotes the export of Adr1 from the nucleus to the cytosol without
      affecting its protein levels. This effect was also observed upon H2O2 treatment,
      but not by iron overload/starvation, indicating the presence of a regulatory
      pathway involved in Adr1 export and inactivation upon stress conditions. We also
      observed that CTH2, a gene involved in the mRNA degradation of several iron
      containing enzymes, was induced upon Yfh1 depletion. Accordingly, decreased
      levels of aconitase and succinate dehydrogenase were observed. Nevertheless,
      their levels were maintained in a Deltacth2 mutant even in the absence of Yfh1.
      From these results we can conclude that, in addition to altering iron
      homeostasis, frataxin depletion involves drastic metabolic remodeling governed by
      Adr1 and Cth2 that finally leads to downregulation of iron-sulfur proteins and
      other proteins involved in respiratory metabolism. 

PMID- 24100162
TI  - The use of the gonadotropin-releasing hormone analog deslorelin for short-term
      contraception in red pandas (Ailurus fulgens).
AB  - Red pandas (Ailurus fulgens) are threatened with extinction owing to habitat
      loss, exacerbated by their unique ecology and low fecundity. Regional breeding
      programs manage captive red panda populations. Recommendations not to breed may
      be made for various reasons, including genetic overrepresentation of certain
      individuals. No recommendations have been published on the use of contraception
      for red pandas. This article discusses the use of the GnRH analog deslorelin as a
      reversible method of contraception in both male and female pandas. The mean time
      from last contraception to conception was 3 years with a 4.6-mg deslorelin
      implant. The average dose of GnRH implant received was 1.09 mg/kg (range, 0.88
      1.32). Males returned to breeding sooner than females. No reproductive side
      effects were noted with up to three consecutive annual GnRH implants. 

PMID- 24100163
TI  - Gonadotropin-releasing hormone immunization for the treatment of urethral
      sphincter mechanism incompetence in ovariectomized bitches.
AB  - We have investigated GnRH immunization for the treatment of urethral sphincter
      mechanism incompetence in ovariectomized bitches. It has been reported that
      decreasing LH secretion through the use of GnRH agonists temporarily restores
      continence in some bitches. Therefore, decreasing the circulating LH
      concentrations by immunizing against GnRH might temporarily maintain continence
      in incontinent dogs. Sixteen incontinent dogs given phenylpropanolamine (PPA) to
      control incontinence were recruited for this study. Eleven dogs were immunized
      against GnRH (novel treatment group) at week 0, and nine dogs were vaccinated
      again 4 weeks later. Five dogs (standard treatment group) were vaccinated with a
      placebo twice at 4-week intervals. PPA was discontinued in the novel treatment
      group 2 weeks after revaccination, and standard-treatment dogs were given PPA for
      the duration of the study. Blood samples were collected before each treatment and
      at 6, 8, 10, 12, 16, 20, and 24 weeks and owners recorded episodes of
      incontinence throughout the study. Ten of the eleven dogs in the novel treatment
      group experienced side effects as a result of vaccination; two of these dogs
      experienced more severe side effects after the first vaccination and were
      withdrawn from the study as a result. Of the nine dogs that completed the
      vaccination series, four dogs remained continent after PPA was discontinued. For
      these four dogs, there was no difference in incontinent episodes when they were
      given PPA versus treatment with the vaccine. All nine novel-treatment dogs
      developed a GnRH antibody titer and experienced a significant decrease in
      circulating LH concentrations. In conclusion, GnRH immunization was effective in
      maintaining continence in four of the nine incontinent ovariectomized dogs, and
      in these dogs, treatment with the vaccine was comparable with treatment with PPA.

PMID- 24100164
TI  - The effect of dietary n-3 polyunsaturated fatty acids supplementation of rams on
      semen quality and subsequent quality of liquid stored semen.
AB  - The objective of this study was to examine the effect of dietary n-3
      polyunsaturated fatty acid (PUFA) supplementation of rams on semen quality and
      subsequent sperm function of liquid stored semen. Mature rams of proven fertility
      were individually housed and were blocked according to breed, body weight, and
      body condition score and randomly allocated within block to one of two dietary
      treatments (N = 7 per treatment). Rams were offered a base diet of hay and
      concentrate, with the concentrate enriched with either: (1) saturated palmitic
      acid (CON) or (2) high n-3 PUFA fish oil (FO) supplements. Both lipid supplements
      were added at 2% (wt/wt) of the total diet as fed and both were partially rumen
      protected. The animals were fed their respective diets for a total of 9 weeks and
      blood samples were collected on weeks 0 (pre-experimental), 4, and 9, relative to
      initial allocation of diet (week 0), for measurement of plasma concentration of
      fatty acids, metabolites, insulin like growth factor 1 (IGF-1) and insulin. Semen
      was collected from each ram (on 1 day in each week) in weeks 4, 5, 7, 8, and 9,
      and each ejaculate was assessed for volume, wave motion, and concentration of
      sperm, after which it was diluted in a skim milk-based extender and stored at 4 
      degrees C. A second ejaculate was collected on weeks 4, 7, and 9, centrifuged,
      and the sperm frozen for subsequent lipid analysis. A sample of semen from each
      ram was assessed at 24, 48, and 72 hours after collection for sperm progressive
      linear motion, ability to penetrate artificial mucus, and the ability to resist
      lipid peroxidation (at 24 and 48 hours only) using the thiobarbituric acid
      reactive substances assay. There was no effect of diet on plasma insulin
      concentrations or on any of the metabolites measured, however, there was a diet
      by week interaction for plasma IGF-1 concentration (P < 0.05). This was
      manifested as the FO supplemented rams having higher IGF-1 concentrations on week
      9 compared with the control treatment (P < 0.05), but not at the earlier sampling
      dates. Compared with the pre-experimental values, supplementation with FO
      increased plasma concentrations of total n-3 PUFAs by 3.1-fold and decreased n-6
      PUFA concentrations by 1.84-fold. Consequently, the ratio of n-6 to n-3 PUFA was
      decreased in the FO-supplemented rams (P < 0.001). Dietary supplementation with
      FO increased the concentration of eicosapentaenoic acid in sperm from week 4 to 9
      by 2.7-fold (P < 0.05) leading to a 1.5-fold increase in total n-3 PUFA in the
      same period. Ejaculates collected from rams supplemented with FO yielded a higher
      semen concentration (P < 0.05), however, there was no difference between diets on
      any of the other semen quality parameters including semen volume, wave motion,
      progressive linear motion, ability to penetrate artificial mucus, or ability to
      resist lipid peroxidation. In conclusion, dietary supplementation of rams with n
      3 PUFA successfully increased the n-3 PUFA content of plasma and sperm but has
      limited effects on the quality of liquid stored semen.

PMID- 24100165
TI  - Normal isometric strength of rotatorcuff muscles in adults.
AB  - OBJECTIVES: The most prevalent disorders of the shoulder are related to the
      muscles of rotator cuff. In order to develop a mechanical method for the
      evaluation of the rotator cuff muscles, we created a database of isometric force
      generation by the rotator cuff muscles in normal adult population. We
      hypothesised the existence of variations according to age, gender and dominancy
      of limb. METHODS: A total of 400 healthy adult volunteers were tested, classified
      into groups of 50 men and women for each decade of life. Maximal isometric force
      was measured at standardised positions for supraspinatus, infraspinatus and
      subscapularis muscles in both shoulders in every person. Torque of the force was
      calculated and normalised to lean body mass. The profiles of mean torque-time
      curves for each age and gender group were compared. RESULTS: Our data showed that
      men gradually gained maximal strength in the fifth decade, and showed decreased
      strength in the sixth. In women the maximal strength was gained in the fourth
      decade with gradual decline to the sixth decade of life. The dominant arm was
      stronger in most of the tested groups. The torque profiles of the rotator cuff
      muscles in men at all ages were significantly higher than that in women.
      CONCLUSIONS: We found previously unrecognised variations of rotator cuff muscles'
      isometric strength according to age, gender and dominancy in a normal population.
      The presented data may serve as a basis for the future studies for identification
      of the abnormal patterns of muscle isometric strength in patients with pathology
      of the rotator cuff muscles. Cite this article: Bone Joint Res 2013;2:214-19.

PMID- 24100166
TI  - Exchange transfusion as a life-saving intervention in three patients with
      different haematological malignancies with severe hyperleukocytosis where
      leukapheresis was not available.
AB  - Hyperleukocytosis is a rare but potentially serious complication of
      haematological malignancies. It is usually treated with rehydration, prevention
      of tumour lysis syndrome and the administration of cytotoxic therapy.
      Leukapheresis may be life-saving in emergency cases. In this article we describe
      how, in a resource-limited setting where leukapheresis was not available, manual
      exchange transfusion was utilised as a life-saving intervention in three patients
      with different haematological malignancies complicated by hyperleukocytosis.
      Further we outline the procedure that was carried out and evaluated possible
      complications associated with this rarely used practice. 

PMID- 24100167
TI  - Involvements of the lateral hypothalamic area in gastric motility and its
      regulation by the lateral septum.
AB  - Ghrelin is an endogenous ligand for the growth hormone secretagogue receptor (GHS
      R) pre-dominantly produced in the stomach. Recent studies have shown that it may
      promote food intake and gastric motility. We aim to explore effects of ghrelin on
      the gastric distension (GD) sensitive neurons and gastric motility in the lateral
      hypothalamic area (LHA), and the possible regulation by the lateral septum.
      Extracellular single unit discharges were recorded and the gastric motility was
      monitored by administration of ghrelin into LHA and electrical stimulation of
      lateral septum. Expression of GHS-R was determined by polymerase chain reaction
      (PCR), western blot and immunohistochemistry staining. Projection of nerve fiber
      and expression of ghrelin were observed by retrograde tracer and fluo
      immunohistochemistry staining. Results revealed that there were GD neurons in the
      LHA, and administration of ghrelin could excite both GD-excitatory (GD-E) and GD
      inhibited (GD-I) neurons in the LHA. The gastric motility was significantly
      promoted by administration of ghrelin into LHA with a dose dependent manner,
      which could be completely abolished by treatment with ghrelin receptor antagonist
      [D-Lys-3]-GHRP-6 or BIM-28163. c-Fos expression was significantly increased after
      ghrelin administration to the LHA. Electrical stimulation of the lateral septum
      could significantly excite GD neurons responsive to ghrelin in the LHA as well as
      promote gastric motility. However, those effects could be absorbed by pre
      treatment of [D-Lys-3]-GHRP-6. GHSR-1a expression in the LHA had no change after
      ghrelin administration to the LHA or electrical stimulating lateral septum.
      Electrical lesion of the LHA resulted in the decrease of gastric motility. GHS-R
      and Ghrelin/FG-double labeled neurons were observed in the LHA and lateral
      septum, respectively. It is suggested that the LHA may involve in promoting
      gastric motility via ghrelin. The Lateral septum projects to the LHA and exerts
      some regulating function on the LHA. 

PMID- 24100168
TI  - Characterization of thyroid hormone receptors during early development of the
      Japanese eel (Anguilla japonica).
AB  - We studied the profiles of thyroid hormone receptors (TRs) in Japanese eels
      (Anguilla japonica) during development from hatched larvae to juveniles. Two
      TRalphas (TRalphaA and TRalphaB) and one TRbeta (TRbetaA) cDNA clones were
      generated by RACE. The TRalphaA, TRalphaB and TRbetaA cDNAs encoded 416, 407 and
      397 amino acid proteins with much higher homologies to the Japanese conger eel
      (Conger myriaster) TRs than to other fish TRs. In a transiently transfected
      Japanese eel cell line, Hepa-E1, the TRs showed thyroid hormone (TH)-dependent
      activation of transcription from the TH-responsive promoter. Four TR cDNA clones,
      including TRbetaB reported in a previous study, were analyzed by real-time RT
      PCR. The TR mRNA levels in hatched larvae were determined. The two TRbeta mRNAs
      were present at low levels but there was a peak in the TRalphas during the larval
      stage before metamorphosis. During metamorphosis, the two TRalphas both exhibited
      peaks and expression of the two TRbetas was higher than during the early growth
      stage. This expression pattern is similar to that of the Japanese conger eel. It
      is possible that thyroid hormones control the early development of Japanese eels
      and Japanese conger eels through TRs. This is the first analysis of the
      expression sequence of TRs during early larval stages of Anguilliformes. 

PMID- 24100169
TI  - Neonatal hypotension: dopamine or dobutamine?
AB  - Controversy surrounds the assessment of perfusion and the methods currently
      utilised to define hypotension, especially blood pressure. There is growing
      agreement to assess heart function when selecting inotropic therapy and use
      bedside tools such as echocardiography for assessing at-risk infants. Both
      dopamine and dobutamine have comparative efficacy, and in certain disease states
      with immature myocardium there could be potential advantages in using dobutamine.
      The concomitant use of hydrocortisone has been shown to be beneficial when
      escalating doses of first-line inotropes are used. Other inotropes require
      further study through randomised trials for their safety and efficacy to be
      established. 

PMID- 24100170
TI  - Interaction of intense femtosecond laser pulses with KDP and DKDP crystals in the
      short wavelength regime.
AB  - We investigate the electronic photo-excitation and relaxation mechanisms involved
      in the optical breakdown of potassium dihydrogen phosphate crystal (KH2PO4) and
      its deuterated form. The dynamics and spectroscopic properties of electron-hole
      pair formation are investigated using time-resolved measurement of the dielectric
      function, and luminescence spectroscopy. The non-common mechanical and electronic
      characteristics of these dielectric materials are revealed by the particular
      structure of ablation craters and also by the complex dynamics observed in the
      relaxation of excited carriers. This relaxation occurs in two steps, and varies
      with the initial carrier density and thus with the laser intensity. We show that
      the defect states play a key role in the excitation pathways, and also determine
      the relaxation stage. The latter also depends upon the initial amount of energy
      of the electron-hole pair after photo-excitation. A model based on kinetic
      equations describing the evolution of the different level populations allows us
      to successfully interpret and reproduce the experimental data. 

PMID- 24100171
TI  - Mortality and causes of death in children referred to a tertiary epilepsy center.
AB  - BACKGROUND: Patients with epilepsy, including children, have an increased
      mortality rate when compared to the general population. Only few studies on
      causes of mortality in childhood epilepsy exist and pediatric SUDEP rate is under
      continuous discussion. AIM: To describe general mortality, incidence of sudden
      unexpected death in epilepsy (SUDEP), causes of death and age distribution in a
      pediatric epilepsy patient population. METHODS: The study retrospectively
      examined the mortality and causes of death in 1974 patients with childhood-onset
      epilepsy at a tertiary epilepsy center in Denmark over a period of 9 years. Cases
      of death were identified through their unique civil registration number.
      Information from death certificates, autopsy reports and medical notes were
      collected. RESULTS: 2.2% (n = 43) of the patient cohort died during the study
      period. This includes 9 patients with SUDEP (8 SUDEP cases per 10,000 patient
      years). 9 patients died in the course of neurodegenerative disease and 28
      children died of various causes. Epilepsy was considered drug resistant in more
      than 95% of the deceased patients, 90% were diagnosed with intellectual
      disability. Mortality of patients that underwent dietary epilepsy treatment was
      slightly higher than in the general cohort. There were no epilepsy-related deaths
      due to drowning. CONCLUSIONS: This study confirms that SUDEP must not be
      disregarded in the pediatric age group. The vast majority of SUDEP cases in this
      study displays numerous risk factors similar to those described in adult epilepsy
      patients. Including SUDEP, only 30% of the mortality was directly seizure
      related.

PMID- 24100172
TI  - Growth and psychomotor development of patients with Duchenne muscular dystrophy.
AB  - Duchenne muscular dystrophy (DMD) is one of the most common hereditary
      degenerative neuromuscular diseases and caused by mutations in the dystrophin
      gene. The objective of the retrospective study was to describe growth and
      psychomotor development of patients with DMD and to detect a possible genotype
      phenotype correlation. Data from 263 patients with DMD (mean age 7.1 years)
      treated at the Departments of Pediatric Neurology in three German University
      Hospitals was assessed with respect to body measurements (length, weight, body
      mass index BMI, head circumference OFC), motor and cognitive development as well
      as genotype (site of mutation). Anthropometric measures and developmental data
      were compared to those of a reference population and deviations were analyzed for
      their frequency in the cohort as well as in relation to the genotypes.
      Corticosteroid therapy was implemented in 29 from 263 patients. Overall 30% of
      the patients exhibit a short statue (length < 3rd centile) with onset early in
      development at 2-5 years of age, and this is even more prevalent when steroid
      therapy is applied (45% of patients with steroid therapy). The BMI shows a
      rightwards shift (68% > 50th centile) and the OFC a leftwards shift (65% < 50th
      centile, 5% microcephaly). Gross motor development is delayed in a third of the
      patients (mean age at walking 18.3 months, 30% > 18 months, 8% > 24 months).
      Almost half of the patients show cognitive impairment (26% learning disability,
      17% intellectual disability). Although there is no strict genotype-phenotype
      correlation, particularly mutations in the distal part of the dystrophin gene are
      frequently associated with short stature and a high rate of microcephaly as well
      as cognitive impairment.

PMID- 24100173
TI  - The effect of continuous intrathecal baclofen on sitting in children with severe
      cerebral palsy.
AB  - AIM: To investigate the effect of intrathecal baclofen (ITB) on sitting in
      children with cerebral palsy with severe spasticity; and identify potential sub
      groups of patients at particular risk of deterioration. METHOD: Twenty three
      children with cerebral palsy, mean age 10 yrs 10 mo were assessed before and
      after ITB treatment using the Sitting dimension of the Gross Motor Function
      Measure. Sitting prior to treatment was compared to sitting following ITB
      treatment in the same children. Exploration of sub groups was also attempted to
      investigate affects of ITB on sitting according to age and severity of motor
      impairment. RESULTS: No significant difference was found in sitting before ITB
      treatment compared to sitting following insertion of an ITB pump (p = 0.09). No
      specific age group or classification of motor impairment demonstrated significant
      deterioration in sitting following ITB treatment. CONCLUSION: Sitting does not
      improve or deteriorate in children following treatment with ITB, independent of
      age or severity of motor impairment.

PMID- 24100175
TI  - Arterial denervation: clinical implications and future perspectives.

PMID- 24100174
TI  - Alternating hemiplegia of childhood in Denmark: clinical manifestations and
      ATP1A3 mutation status.
AB  - Alternating hemiplegia of childhood (AHC) is a rare neurodevelopmental disorder
      characterized by early-onset recurrent distinctive hemiplegic episodes commonly
      accompanied by other paroxysmal features and developmental impairment. De novo
      mutations in ATP1A3 were recently identified as a genetic cause of AHC. To
      describe the entire Danish cohort of paediatric AHC patients we approached
      neuropaediatricians nationwide. All currently acknowledged Danish patients <=16
      years with AHC were genetically tested and seen by the same child neurologist
      (PU). Ten patients; seven girls and three boys were identified. Mean present age
      was 10.0 years (range 1-16). Mean age at presentation was 7.4 months (range 1-18
      months). Sequencing of ATP1A3 in all ten patients revealed a pathogenic mutation
      in seven. Two females with moderate psychomotor impairment were heterozygous for
      the known p.G947R mutation, whereas one severely retarded boy was heterozygous
      for the common p.E815K mutation. The prevalent p.D801N mutation was identified in
      two moderate to severely retarded children. Interestingly, in a set of
      monochorionic male twins a novel p.D801E mutation was identified, underscoring
      that the asparagine at position 801 is a mutation hotspot. Three girls aged 5-13
      years did not reveal any ATP1A3 mutations. They were rather mildly clinically
      affected and displayed a normal or near-normal psychomotor development. This is
      the first study of AHC in the Danish paediatric population. The patients
      harboured a wide range of psychomotor difficulties. Patients with no mutation
      detected tended to be less severely affected. Prevalence was approximately 1 per
      100,000 children.

PMID- 24100177
TI  - Clinical characteristics of patients with acute coronary syndrome at high
      clinical suspicion for obstructive sleep apnea syndrome.
AB  - INTRODUCTION: The risk of a cardiovascular event increases with the number of
      cardiovascular risk factors. The aim of this study was to identify patients with
      acute coronary syndromes (ACS) who were at high clinical suspicion for
      obstructive sleep apnea syndrome (OSAS). We also report the clinical
      characteristics of ACS patients at high clinical suspicion for OSAS. METHODS: We
      studied 158 consecutive patients who satisfied the entry criteria (mean age 57.1
      +/- 8.7 years, 68% males) and were admitted to a tertiary university hospital.
      The risk of OSAS was assessed using the Berlin questionnaire. In addition, all
      patients were required to have excessive sleepiness as demonstrated by a score
      >10 on the Epworth Sleepiness Scale (ESS). RESULTS: Fifty four (34.2%) patients
      were at high clinical suspicion. On admission, patients at clinical suspicion for
      OSAS had significantly more often a history of hypertension (92.6% vs. 55.8%,
      p<0.0001) or diabetes mellitus (37% vs. 15.4%, p=0.0049); significantly higher
      mean ESS (14.83 +/- 3.02 vs. 5.83 +/- 3.33, p<0.0001), systolic blood pressure
      (149.9 +/- 34.2 vs. 128.4 +/- 23.6 mmHg, p<0.0001), diastolic blood pressure
      (87.7 +/- 17.4 vs. 76.2 +/- 12.1 mmHg, p<0.0001), and body mass index (32.3 +/-
      4.6 vs. 27 +/- 3.8 kg/m(2), p<0.0001); and a lower glomerular filtration rate
      (79.5 +/- 21.2 vs. 87.5 +/- 22.2 ml/min/1.73 m(2), p=0.048). Patients at high
      clinical suspicion for OSAS more often had onset of acute chest pain between
      midnight and 5.59 am compared to the patients at low clinical suspicion (42.6%
      vs. 26%; p<0.05). The mortality (7.4% vs. 1%; p=0.03) was greater in patients at
      high clinical suspicion. CONCLUSIONS: This study demonstrates that one out of
      every three ACS patients was diagnosed with a high clinical suspicion for OSAS.
      The prevalence of cardiovascular risk factors among ACS patients at high clinical
      suspicion for OSAS was high when compared with patients at low clinical
      suspicion. This finding calls for physicians to perform routine screening and
      individual evaluation of myocardial infarction patients for sleep disorders,
      especially when they are obese, or have hypertension or chest pain in the night
      hours.

PMID- 24100176
TI  - Beta2-adrenergic activation via administration of atenolol/formoterol combination
      increases contractility and coronary blood flow in isolated rat hearts.
AB  - INTRODUCTION: Commonly used adrenergic agonists in low cardiac output scenarios
      rely primarily on beta1adrenergic activation to stimulate cardiac function.
      Little is known about the use of beta2-adrenergic agonist administration for this
      purpose, although the associated vasodilation may be beneficial. This study was
      conducted in order to assess the efficacy of one such beta2-adrenergic agonist,
      formoterol, in augmenting cardiac function. METHODS: The hearts of 8 anesthetized
      female Wistar rats were excised, and subsequently kept functional in an isolated
      heart preparation (Langendorff apparatus). After placement on the apparatus,
      hearts were subjected to the beta1-blocker, atenolol, and then to a combination
      of formoterol/atenolol. Left ventricular developed pressure (LVDP), heart rate
      (HR), and coronary flow (CF) were monitored. RESULTS: CF showed a median increase
      of 16% (p<0.05) after formoterol/atenolol administration, with this effect
      lasting 20 min post-administration. Furthermore, statistically significant
      differences included an early 26% increase in LVDP and a late 21% increase in HR.
      The CF increase was independent of HR and LVDP changes. CONCLUSIONS: Our results
      indicate that the beta2-agonist formoterol not only successfully increases heart
      rate and contractility, but also increases coronary flow, most likely by means of
      beta2-mediated coronary vasodilation. This pharmacological profile may prove to
      be especially beneficial in situations where cardiac output must be increased,
      while adequate myocardial oxygen delivery needs to be maintained.

PMID- 24100178
TI  - The Greek cardiac magnetic resonance experience: a comparison with the EuroCMR
      Registry.
AB  - INTRODUCTION: We carried out an evaluation of Greek cardiovascular magnetic
      resonance (CMR) data in order to analyse the indications, safety, quality, and
      impact on management, in comparison with the EuroCMR registry. METHODS: A
      retrospective analysis was performed of Greek CMR data from patients referred
      from 6 Greek cardiac clinics to 6 different MRI units in Athens that offer CMR
      services. A total of 10,000 CMR examinations carried out from 1995 to 2010 were
      evaluated retrospectively and included in the study. RESULTS: Fifty percent of
      patients underwent evaluation for thalassaemic syndromes. In the remaining 50%,
      the most important indications were: a) workup of myocarditis/cardiomyopathies
      (40%), b) assessment of viability (5%), and c) congenital heart disease (5%).
      Image quality was good in 75%, moderate in 15%, and inadequate in 10% of cases.
      Complications occurred in 0.02%, including allergic reactions, dyspnoea, and
      panic attack. No death or cardiac complication was observed during or due to CMR;
      however, stress testing was not used in any of the cases. In 65% of all CMR
      studies, the initial diagnosis made by a non SCMR-trained person had no impact on
      the patients' management and did not offer any diagnostic contribution to
      referral clinicians, discouraging them from referring for CMR again. However,
      after the re-evaluation performed by an SCMR-trained person, the results of the
      Greek CMR were capable of satisfying all imaging needs in a percentage of
      patients equivalent to that presented in the EuroCMR registry (83% vs. 86%,
      p=NS), so that no further non-invasive imaging procedures would be required after
      CMR. CONCLUSIONS: Thalassaemia and myocarditis were the most frequent CMR
      indications in Greece. However, the lack of training according to SCMR guidelines
      lowers the diagnostic efficacy significantly and leads to under-use of the
      technique.

PMID- 24100179
TI  - Prevalence of "distressed" personality in patients with coronary artery disease
      and its correlation with morbidity after coronary surgery.
AB  - INTRODUCTION: The "distressed" (Type-D) personality is an emerging risk factor in
      cardiovascular diseases and is associated with an increased risk of impaired
      quality of life, morbidity and mortality. The purpose of this study was to
      explore the prevalence of Type-D personality among patients with coronary artery
      disease (CAD) and its association with the development of complications following
      coronary artery bypass grafting surgery. METHODS: A Greek version of the Type-D
      Personality Scale-14 (DS14), along with the Hospital Anxiety and Depression Scale
      (HADS) as well as the Ways of Coping Questionnaire (WCQ), were used. A cohort of
      323 patients with CAD was examined. RESULTS: The prevalence of Type-D personality
      among Greek patients with CAD was found to be 18.24%. Type-D patients showed a
      higher rate of anxiety and depression compared to non Type-D patients. Type-D was
      also associated with passive coping and negatively correlated with active coping.
      Regarding postoperative morbidity, type-D patients were at an increased risk of
      developing postoperative atrial fibrillation, while no significant differences
      were found in the development of any other complication. CONCLUSIONS: The impact
      of Type-D personality on health outcomes should be studied further, both in
      clinical samples and in the general population.

PMID- 24100180
TI  - Clinical profile and therapeutic management of patients with atrial fibrillation
      in Greece: results from the Registry of Atrial Fibrillation to Investigate New
      Guidelines (RAFTING).
AB  - INTRODUCTION: Atrial fibrillation (AF) is the most common arrhythmia with
      significant morbidity, including a 5-fold increase in stroke risk. The management
      of AF, including antithrombotic therapy (AT), varies considerably among
      countries. Representative data concerning AF features and management in Greece
      are generally lacking. METHODS: The Registry of Atrial Fibrillation To
      Investigate New Guidelines (RAFTING) is a country-wide prospective observational
      study of AF in Greece that enrolled consecutive patients with a diagnosis of AF
      in emergency departments of 31 hospitals of different types according to the
      population's geographical distribution. RESULTS: RAFTING enrolled 1127 patients,
      51% females, aged 71 +/- 12 years. Paroxysmal AF was present in 54% of patients
      and newly diagnosed AF in 28%; 68% of patients with a previous AF history had
      undergone a median of 4 cardioversions. A high rate of comorbidities was present,
      including arterial hypertension in 75% and heart failure in 40%. The median
      CHADS2 and CHA2DS2VASc scores were 2 and 3, respectively; AT had been prescribed
      in 87% of non-newly diagnosed patients, with warfarin being prescribed in 56% of
      them. Among all patients on warfarin, INR values were within therapeutic range in
      34% of cases during inhospital measurement. Hospital admission occurred in 82% of
      cases, with in-hospital mortality 0.8%. CONCLUSIONS: RAFTING provides updated
      insights into the current features and management of AF in Greece. The majority
      of patients have a sufficiently high risk to warrant oral anticoagulation and
      further attempts to comply with the existing guidelines are warranted.

PMID- 24100181
TI  - Reuse of devices in cardiology: time for a reappraisal.

PMID- 24100182
TI  - Epidemiology and diagnosis of viral myocarditis.

PMID- 24100183
TI  - Supravalvular aortic stenosis in homozygous familial hypercholesterolemia.

PMID- 24100184
TI  - Endocardial late potentials during sinus rhythm define the re-entry circuit of
      ventricular tachycardia in arrhythmogenic right ventricular cardiomyopathy.
AB  - Arrhythmogenic right ventricular cardiomyopathy/dysplasia (ARVC/D) is an
      inherited cardiomyopathy characterized by progressive fibro-fatty replacement of
      the right ventricular myocardium. We report a case where mapping of endocardial
      potentials during sinus rhythm identified the re-entry circuit of a recurrent
      ventricular tachycardia in a patient with ARVC. The tachycardia was subsequently
      ablated successfully. 

PMID- 24100185
TI  - Transapical closure of mitral prosthetic paravalvular leak.
AB  - Clinically significant mitral prosthetic paravalvular leaks may occur in up to 5%
      of patients following surgical mitral valve replacement. Successful closure may
      offer relief from symptoms of heart failure and hemolysis, but surgical closure
      is associated with increased morbidity and mortality. Alternative transcatheter
      closure techniques are being developed. We present a patient who was successfully
      treated via a transapical approach with deployment of an amplatzer duct occluder
      type I closure device under real-time two-dimensional transesophageal
      echocardiography.

PMID- 24100186
TI  - Percutaneous coronary intervention and stenting in a single coronary artery
      originating from the right sinus of valsalva.
AB  - Percutaneous revascularisation in anomalous coronary arteries poses certain
      technical difficulties, especially in the selective cannulation of the diseased
      vessel and the coaxial positioning of the guiding catheter for optimum stability.
      We report a case of successful stent implantation in a single coronary artery
      (SCA) arising from the right sinus of Valsalva (SoV). The ART 4 (Boston
      Scientific) guiding catheter provided excellent back-up support for stent
      delivery in the diseased circumflex artery. We also discuss the anatomical
      variations of an SCA originating from the right SoV, their angiographic
      recognition, the clinical implications, as well as technical considerations that
      should be taken into account when performing percutaneous interventions in these
      vessels. 

PMID- 24100187
TI  - Left atrial appendage occlusion with the Amplatzer Amulet for stroke prevention
      in atrial fibrillation: the first case in Greece.
AB  - Left atrial appendage (LAA) occlusion has been introduced into clinical practice
      as a valuable alternative to oral anticoagulation for stroke prevention in
      patients with non-valvular atrial fibrillation. In this case presentation we
      describe the first LAA occlusion in Greece using the Amplatzer Amulet device. We
      also briefly discuss issues related to procedural safety and multimodality
      imaging for LAA occlusion. 

PMID- 24100188
TI  - Arterial hypertension.

PMID- 24100189
TI  - Risk stratification for stroke: do we need new tools?

PMID- 24100190
TI  - Decoupling factors affecting plant diversity and cover on extensive green roofs.
AB  - Supplemental irrigation systems are often specified on green roofs to ensure
      plant cover and growth, both important components of green roof performance and
      aesthetics. Properties of the growing media environment too can alter the
      assemblage of plant species able to thrive. In this study we determine how plant
      cover, above ground biomass and species diversity are influenced by irrigation
      and growing media. Grass and forb vegetative cover and biomass were significantly
      greater in organic based growing media but there was no effect of supplemental
      irrigation, with two warm season grasses dominating in those treatments receiving
      no supplemental irrigation. On the other hand, plant diversity declined without
      irrigation in organic media, and having no irrigation in inorganic growing media
      resulted in almost a complete loss of cover. Sedum biomass was less in inorganic
      growing media treatments and species dominance shifted when growing media organic
      content increased. Our results demonstrate that supplemental irrigation is
      required to maintain plant diversity on an extensive green roof, but not
      necessarily plant cover or biomass. These results provide evidence that planting
      extensive green roofs with a mix of plant species can ensure the survival of some
      species; maintaining cover and biomass when supplemental irrigation is turned off
      to conserve water, or during extreme drought. 

PMID- 24100191
TI  - Pretreatment of aripiprazole and minocycline, but not haloperidol, suppresses
      oligodendrocyte damage from interferon-gamma-stimulated microglia in co-culture
      model.
AB  - Recent imaging studies have indicated that the pathophysiology of schizophrenia
      is closely related to white matter abnormalities and microglial activation.
      Additionally, recent clinical trials have suggested that atypical antipsychotics
      may have brain protective properties and that minocycline, an antibiotic with
      inhibitory effects on microglial activation, improves symptoms of schizophrenia.
      We have reported that not only atypical antipsychotics with dopamine D2 receptor
      (D2R) antagonism but also aripiprazole, a unique antipsychotic drug with D2R
      partial agonism, inhibit microglial activation in vitro. Thus, atypical
      antipsychotics may exert a beneficial influence on both microglia and
      oligodendrocytes, while the underlying mechanisms have not been clarified. Here,
      we investigated whether antipsychotics suppress oligodendrocyte damage by
      inhibiting microglial activation utilizing a co-culture model with microglia and
      oligodendrocytes. Pretreatment of aripiprazole and minocycline suppressed
      apoptosis of oligodendrocytes in the co-culture model with interferon-gamma (IFN
      gamma)-activated microglia, while haloperidol, a traditional antipsychotic drug,
      did not. Aripiprazole and minocycline inhibited the production of tumor necrosis
      factor-alpha (TNF-alpha) from IFN-gamma-activated microglia. Moreover,
      aripiprazole and minocycline attenuated the phosphorylation of signal transducer
      and activator of transcription 1 (STAT1) in microglia. Overall, our results
      suggest that aripiprazole and minocycline may have antipsychotic effects through
      reducing oligodendrocyte damage caused by microglial activation. These results
      put forward a novel therapeutic hypothesis in schizophrenia research. Future in
      vivo studies to confirm the present results should be performed.

PMID- 24100192
TI  - Bedside to bench: role of muscarinic receptor activation in ultrarapid growth of
      colorectal cancer in a patient with pheochromocytoma.
AB  - An elderly man with long-standing, nonresectable pheochromocytoma had rapid
      development of rectal adenocarcinoma despite close endoscopic surveillance. We
      determined that the patient's colorectal cancer overexpressed muscarinic receptor
      subtype 3, whereas his pheochromocytoma expressed choline acetyltransferase, an
      enzyme required to produce acetylcholine, which is a muscarinic receptor agonist.
      These findings suggested that acetylcholine release from the pheochromocytoma
      stimulated rapid growth of the rectal neoplasm. As proof of principle, we found
      that culture media conditioned by pheochromocytoma cells stimulates proliferation
      of a human colon cancer cell line, an effect attenuated by atropine, a muscarinic
      receptor inhibitor. Our observations provide both clinical and laboratory
      evidence that muscarinic receptor agonists promote the growth of colorectal
      neoplasia. 

PMID- 24100193
TI  - Motivation for physical activity in children: a moving matter in need for study.
AB  - Motivation for physical activity in children below the age of 12 years is a
      largely underrepresented issue in contemporary research. Although engagement in
      sufficient physical activity is highly important for children's current and later
      health, relatively little is known of the factors that motivate children to be
      physically active. Various theories have been developed in an attempt to explain
      motivation toward physical activity in adults. Recent developments have focussed
      on integrating constructs of these theories in order to attain a comprehensive
      account of motivated behavior. The relationships between different motivational
      constructs have generally been investigated in healthy adolescents and adults.
      This manuscript outlines why more theoretically driven research into children's
      motivation toward physical activity is needed. Constructs stemming from various
      motivational theories and their interrelationship as evidenced in youth and
      adults will be summarized. The current state of research on the applicability of
      these motivational constructs to children, and the generalizability of the
      interrelationship between the constructs to child samples will be outlined. A
      deeper insight into the motivational determinants of physical activity
      participation in children could inform the design of interventions to facilitate
      the development of physically active lifestyles that persist at older ages.

PMID- 24100194
TI  - Possible role of an error detection mechanism in brain processing of deception:
      PET-fMRI study.
AB  - To investigate brain maintenance of deliberate deception the positron emission
      tomography and the event related functional MRI studies were performed. We used
      an experimental paradigm that presupposed free choices between equally beneficial
      deceptive or honest actions. Experimental task simulated the "Cheat" card game
      which aims to defeat an opponent by sequential deceptive and honest claims.
      Results of both the PET and the fMRI studies revealed that execution of both
      deliberately deceptive and honest claims is associated with fronto-parietal brain
      network comprised of inferior and middle frontal gyri, precentral gyrus (BA 6),
      caudate nucleus, and inferior parietal lobule. Direct comparison between those
      claims, balanced in terms of decision making and action outcome (gain and
      losses), revealed activation of areas specifically associated with deception
      execution: precentral gyrus (BA 6), caudate nuclei, thalamus and inferior
      parietal lobule (BA 39/40). The obtained experimental data were discussed in
      relation to a possible role of an error detection system in processing deliberate
      deception. 

PMID- 24100196
TI  - Reduced CCK signaling in obese-prone rats fed a high fat diet.
AB  - Deficits in satiation signaling during obesogenic feeding have been proposed to
      play a role in hyperphagia and weight gain in animals prone to become obese.
      However, whether this impaired signaling is due to high fat (HF) feeding or to
      their obese phenotype is still unknown. Therefore, in the current study, we
      examined the effects of CCK-8 (0.5, 1.0, 2.0, and 4.0 MUg/kg) on suppression of
      food intake of HF-fed obese prone (OP) and resistant (OR) rats. Additionally, we
      determined the role of endogenous CCK in lipid-induced satiation by measuring
      plasma CCK levels following a lipid gavage, and tested the effect of pretreatment
      with devazepide, a CCK-1R antagonist on intragastric lipid-induced satiation.
      Finally, we examined CCK-1R mRNA levels in the nodose ganglia. We show that OP
      rats have reduced feeding responses to the low doses of exogenous CCK-8 compared
      to OR rats. Furthermore, OP rats exhibit deficits in endogenous CCK signaling, as
      pretreatment with devazepide failed to abolish the reduction in food intake
      following lipid gavage. These effects were associated with reduced plasma CCK
      after intragastric lipid in OP but not OR rats. Furthermore, HF feeding resulted
      in downregulation of CCK-1Rs in the nodose ganglia of OP rats. Collectively,
      these results demonstrate that HF feeding leads to impairments in lipid-induced
      CCK satiation signaling in obese-prone rats, potentially contributing to
      hyperphagia and weight gain.

PMID- 24100195
TI  - Transgenerational effects of prenatal bisphenol A on social recognition.
AB  - Bisphenol A (BPA) is a man-made endocrine disrupting compound used to manufacture
      polycarbonate plastics. It is found in plastic bottles, canned food linings,
      thermal receipts and other commonly used items. Over 93% of people have
      detectable BPA levels in their urine. Epidemiological studies report correlations
      between BPA levels during pregnancy and activity, anxiety, and depression in
      children. We fed female mice control or BPA-containing diets that produced plasma
      BPA concentrations similar to concentrations in humans. Females were mated and at
      birth, pups were fostered to control dams to limit BPA exposure to gestation in
      the first generation. Sibling pairs were bred to the third generation with no
      further BPA exposure. First (F1) and third (F3) generation juveniles were tested
      for social recognition and in the open field. Adult F3 mice were tested for
      olfactory discrimination. In both generations, BPA exposed juvenile mice
      displayed higher levels of investigation than controls in a social recognition
      task. In F3 BPA exposed mice, dishabituation to a novel female was impaired. In
      the open field, no differences were noted in F1 mice, while in F3, BPA lineage
      mice were more active than controls. No impairments were detected in F3 mice, all
      were able to discriminate different male urine pools and urine from water. No sex
      differences were found in any task. These results demonstrate that BPA exposure
      during gestation has long lasting, transgenerational effects on social
      recognition and activity in mice. These findings show that BPA exposure has
      transgenerational actions on behavior and have implications for human
      neurodevelopmental behavioral disorders.

PMID- 24100197
TI  - Functional significance of a phylogenetically widespread sexual dimorphism in
      vasotocin/vasopressin production.
AB  - Male-biased production of arginine vasotocin/vasopressin (VT/VP) in the medial
      bed nucleus of the stria terminalis (BSTm) represents one of the largest and most
      phylogenetically widespread sexual dimorphisms in the vertebrate brain. Although
      this sex difference was identified 30 years ago, the function of the dimorphism
      has yet to be determined. Because 1) rapid transcriptional activation of BSTm
      VT/VP neurons is observed selectively in response to affiliation-related stimuli,
      2) BSTm VT/VP content and release correlates negatively with aggression, and 3)
      BSTm VT/VP production is often limited to periods of reproduction, we
      hypothesized that the sexual dimorphism serves to promote male-specific
      reproductive behaviors and offset male aggression in the context of reproductive
      affiliation. We now show that antisense knockdown of BSTm VT production in colony
      housed finches strongly increases aggression in a male-specific manner and
      concomitantly reduces courtship. Thus, the widespread dimorphism may serve to
      focus males on affiliation in appropriate reproductive contexts (e.g., when
      courting) while concomitantly offsetting males' tendency for greater aggression
      relative to females.

PMID- 24100198
TI  - Sampling of illicit drugs for quantitative analysis--part II. Study of particle
      size and its influence on mass reduction.
AB  - The basic goal in sampling for the quantitative analysis of illicit drugs is to
      maintain the average concentration of the drug in the material from its original
      seized state (the primary sample) all the way through to the analytical sample,
      where the effect of particle size is most critical. The size of the largest
      particles of different authentic illicit drug materials, in their original state
      and after homogenisation, using manual or mechanical procedures, was measured
      using a microscope with a camera attachment. The comminution methods employed
      included pestle and mortar (manual) and various ball and knife mills
      (mechanical). The drugs investigated were amphetamine, heroin, cocaine and herbal
      cannabis. It was shown that comminution of illicit drug materials using these
      techniques reduces the nominal particle size from approximately 600 MUm down to
      between 200 and 300 MUm. It was demonstrated that the choice of 1 g increments
      for the primary samples of powdered drugs and cannabis resin, which were used in
      the heterogeneity part of our study (Part I) was correct for the routine
      quantitative analysis of illicit seized drugs. For herbal cannabis we found that
      the appropriate increment size was larger. Based on the results of this study we
      can generally state that: An analytical sample weight of between 20 and 35 mg of
      an illicit powdered drug, with an assumed purity of 5% or higher, would be
      considered appropriate and would generate an RSDsampling in the same region as
      the RSDanalysis for a typical quantitative method of analysis for the most
      common, powdered, illicit drugs. For herbal cannabis, with an assumed purity of
      1% THC (tetrahydrocannabinol) or higher, an analytical sample weight of
      approximately 200 mg would be appropriate. In Part III we will pull together our
      homogeneity studies and particle size investigations and use them to devise
      sampling plans and sample preparations suitable for the quantitative instrumental
      analysis of the most common illicit drugs.

PMID- 24100199
TI  - Educating international students about tuberculosis and infections associated
      with travel to visit friends and relatives (VFR-travel).
AB  - BACKGROUND: International students in Victoria, Australia, originate from over
      140 different countries. They are over-represented in disease notifications for
      tuberculosis and travel-associated infections, including enteric fever, hepatitis
      A, and malaria. We describe a public health initiative aimed to increase
      awareness of these illnesses among international students and their support
      staff. METHODS: We identified key agencies including student support advisors,
      medical practitioners, health insurers, and government and professional
      organisations. We developed health education materials targeting international
      students regarding tuberculosis and travel-related infections to be disseminated
      via a number of different media, including electronic and printed materials. We
      sought informal feedback from personnel in all interested agencies regarding the
      materials developed, their willingness to deliver these materials to
      international students, and their preferred media for disseminating these
      materials. RESULTS: Education institutions with dedicated international student
      support staff and on-campus health clinics were more easily engaged to provide
      feedback and disseminate the health education materials than institutions without
      such dedicated personnel. Response to contacting off-campus medical practices was
      poor. Delivery of educational materials via electronic and social media was
      preferred over face-to-face education. CONCLUSIONS: It is feasible to provide
      health education messages targeting international students for dissemination via
      appropriately-staffed educational institutions. This initiative could be expanded
      in terms of age-group, geographic range, and health issues to be targeted.

PMID- 24100200
TI  - Emergence of co-infection of visceral leishmaniasis in HIV-positive patients in
      northeast Iran: a preliminary study.
AB  - Visceral leishmaniasis (VL) serosurvey was carried out on 49 HIV/AIDS patients
      among 500 asymptomatic HIV/infected patients who registered in the Khorasan
      Razavi Province during the last 14 years. HIV infections were detected by ELISA
      and confirmed using western blot assay at the AIDS centre of the Khorasan Razavi
      Province. All collected sera were screened using the direct agglutination test
      (DAT). The sera with anti-Leishmania infantum antibodies at a titre of 1:100 were
      considered positive for VL infection and serum titration was performed from 1:100
      to 1:102,400. Nine (18.4%) patients were sero-positive according to DAT. The
      distribution of sera titrations were as follows: 1:100 (n = 6) 1:1600 (n = 1);
      1:25,600 (n = 1) and 1:102,400 (n = 1). All sero-positive cases showed clinical
      signs and symptoms. The most predominant signs and symptoms of co-infection of
      visceral leishmaniasis in HIV-positive patients were pneumonia (n = 2),
      hepatosplenomegaly (n = 2), lymphadenopathy (n = 2), anaemia (n = 1), prolonged
      fever (n = 1) and cachexia (n = 1). Our finding shows that VL (or kala-azar) is
      an opportunistic disease in HIV-positive patients that may be occurred in VL
      endemic areas of Iran.

PMID- 24100201
TI  - [18F]FMeNER-D2: reliable fully-automated synthesis for visualization of the
      norepinephrine transporter.
AB  - PURPOSE: In neurodegenerative diseases and neuropsychiatric disorders
      dysregulation of the norepinephrine transporter (NET) has been reported. For
      visualization of NET availability and occupancy in the human brain PET imaging
      can be used. Therefore, selective NET-PET tracers with high affinity are
      required. Amongst these, [(18)F]FMeNER-D2 is showing the best results so far.
      Furthermore, a reliable fully automated radiosynthesis is a prerequisite for
      successful application of PET-tracers. The aim of this work was the automation of
      [(18)F]FMeNER-D2 radiolabelling for subsequent clinical use. The presented study
      comprises 25 automated large-scale syntheses, which were directly applied to
      healthy volunteers and adult patients suffering from attention deficit
      hyperactivity disorder (ADHD). PROCEDURES: Synthesis of [(18)F]FMeNER-D2 was
      automated within a Nuclear Interface Module. Starting from 20-30 GBq
      [(18)F]fluoride, azeotropic drying, reaction with Br2CD2, distillation of 1-bromo
      2-[(18)F]fluoromethane-D2 ([(18)F]BFM) and reaction of the pure [(18)F]BFM with
      unprotected precursor NER were optimized and completely automated. HPLC
      purification and SPE procedure were completed, formulation and sterile filtration
      were achieved on-line and full quality control was performed. RESULTS: Purified
      product was obtained in a fully automated synthesis in clinical scale allowing
      maximum radiation safety and routine production under GMP-like manner. So far,
      more than 25 fully automated syntheses were successfully performed, yielding 1.0
      2.5 GBq of formulated [(18)F]FMeNER-D2 with specific activities between 430 and
      1707 GBq/MUmol within 95 min total preparation time. CONCLUSIONS: A first fully
      automated [(18)F]FMeNER-D2 synthesis was established, allowing routine production
      of this NET-PET tracer under maximum radiation safety and standardization.

PMID- 24100202
TI  - Noninvasive assessment of alveolar microvascular recruitment in conscious non
      sedated rats.
AB  - Recruitment of alveolar microvascular reserves, assessed from the relationship
      between pulmonary diffusing capacity (DLCO) and perfusion (Qc), is critical to
      the maintenance of arterial blood oxygenation. Leptin-resistant ZDF fatty
      diabetic (fa/fa) rats exhibit restricted cardiopulmonary physiology under
      anesthesia. To assess alveolar microvascular function in conscious, non-sedated,
      non-instrumented, and minimally restrained animals, we adapted a rebreathing
      technique to study fa/fa and control non-diabetic (+/+) rats (4-5 and 7-11mo old)
      at rest and during mild spontaneous activity. Measurements included O2 uptake,
      lung volume, Qc, DLCO, membrane diffusing capacity (DMCO), capillary blood volume
      (Vc) and septal tissue-blood volume. In older fa/fa than +/+ animals, DLCO and
      DMCO at a given Qc were lower; Vc was reduced in proportion to Qc. Results
      demonstrate the consequences of alveolar microangiopathy in the metabolic
      syndrome: lung volume restriction, reduced Qc, and elevated membrane resistance
      to diffusion. At a given Qc, DLCO is lower in rats and guinea pigs than dogs or
      humans, consistent with limited alveolar microvascular reserves in small animals.

PMID- 24100203
TI  - Muscle-chimaeric medial sural artery perforator flap: a new design for complex
      three-dimensional knee defect.
AB  - Reconstructions of composite and three-dimensional knee defects remain
      challenging. Gastrocnemius musculocutaneous flaps have been widely used for
      complex knee-defect reconstruction, but problems of donor-site morbidity and
      bulkiness of flaps remain. In the present study, we designed a new muscle
      chimaeric medial sural artery perforator flap and applied the technique in a
      clinical case. A gastrocnemius muscle segment with sufficient pedicle length was
      obtained by intramuscular dissection of the vascular pedicle. The muscle segment
      was then utilised to fill the underlying dead space and the remaining soft tissue
      and skin defects were reconstructed with the perforator skin flap. The flap
      survived completely and wound healing progressed smoothly without infection,
      haematoma or seroma. Our patients were satisfied with their aesthetic outcomes
      and did not experience any donor-site morbidity. The muscle-chimaeric medial
      sural artery perforator flap is a valuable option for the reconstruction of
      composite and three-dimensional knee defects. 

PMID- 24100204
TI  - To Mohs or not to Mohs.
AB  - BACKGROUND: The preferred method of treatment of Dermatofibrosarcoma Protuberance
      (DFSP) is surgery. Clear margins are achieved by wide local excision (WLE) or by
      Mohs micrographic surgery. Mohs surgery and reconstruction always requires two or
      more procedures. This study aims to assess the ability of WLE to accomplish clear
      histopathological margins and low recurrence rate with a single procedure. We
      present our results from ten years experience of wide local excision. METHODS:
      This is a retrospective analysis of data of all cases of DFSP treated with WLE by
      a single operator in our department between 2002 and 2012. RESULTS: Twenty
      patients were identified. The surgical excision and reconstruction were performed
      on the same day in all cases. The mean histological peripheral margin was 17 mm
      and the deep 9 mm. There was no incomplete excision and no recurrence recorded.
      There were no postoperative complications or tumour recurrences reported for an
      average period of 5.6 years follow-up. CONCLUSION: Mohs surgery offers clear
      histological margins but requires multiple patient visits to achieve complete
      excision and later reconstruction. We show that WLE can achieve these in one
      procedure, the excision margins making little difference when planning the
      eventual reconstruction.

PMID- 24100205
TI  - Breast implant information identification: betadine smear.

PMID- 24100207
TI  - Modelling the fate of nonylphenolic compounds in the Seine River--part 1:
      determination of in-situ attenuation rate constants.
AB  - Assessing the fate of endocrine disrupting compounds (EDCs) in the environment is
      currently a key issue for determining their impacts on aquatic ecosystems. The 4
      nonylphenol (4-NP) is a well known EDC and results from the biodegradation of
      surfactant nonylphenol ethoxylates (NPnEOs). Fate mechanisms of NPnEO are well
      documented but their rate constants have been mainly determined through
      laboratory experiments. This study aims at evaluating the in-situ fate of 4-NP,
      nonylphenol monoethoxylate (NP1EO) and nonylphenolic acetic acid (NP1EC). Two
      sampling campaigns were carried out on the Seine River in July and September
      2011, along a 28km-transect downstream Paris City. The field measurements are
      used for the calibration of a sub-model of NPnEO fate, included into a hydro
      ecological model of the Seine River (ProSe). The timing of the sampling is based
      on the Seine River velocity in order to follow a volume of water. Based on our
      results, in-situ attenuation rate constants of 4-NP, NP1EO and NP1EC for both
      campaigns are evaluated. These rate constants vary greatly. Although the
      attenuation rate constants in July are especially high (higher than 1d(-1)),
      those obtained in September are lower and consistent with the literature. This is
      probably due to the biogeochemical conditions in the Seine River. Indeed, the
      July sampling campaign took place at the end of an algal bloom leading to an
      unusual bacterial biomass while the September campaign was carried out during
      common biogeochemical status. Finally, the uncertainties on measurements and on
      the calibration parameters are estimated through a sensitivity analysis. This
      study provides relevant information regarding the fate of biodegradable
      pollutants in an aquatic environment by coupling field measurements and a
      biogeochemical model. Such data may be very helpful in the future to better
      understand the fate of nonylphenolic compounds or any other pollutants at the
      basin scale. 

PMID- 24100206
TI  - The association of bisphenol-A urinary concentrations with antral follicle counts
      and other measures of ovarian reserve in women undergoing infertility treatments.
AB  - In this prospective cohort of women undergoing infertility treatments, we
      measured specific-gravity adjusted urinary BPA (SG-BPA) concentrations and used
      regression models to evaluate the association of BPA with antral follicle count
      (AFC), day-3 serum follicle stimulating hormone levels (FSH), and ovarian volume
      (OV). BPA, detected in >80% of women, had a geometric mean (+/-GSD) of 1.6+/-2.0,
      1.7+/-2.1, and 1.5+/-1.8MUg/L for the women contributing to the AFC (n=154), day
      3 FSH (n=120), and OV (n=114) analyses, respectively. There was an average
      decrease in AFC of 12% (95% CI: -23%, -0.6%), 22% (95% CI: -31%, -11%), and 17%
      (95% CI: -27%, -6%), in the 2nd, 3rd, and 4th SG-BPA quartile compared to the 1st
      quartile, respectively (p-trend: <0.001). No association of SG-BPA with FSH or OV
      was observed. Among women from an infertility clinic, higher urinary BPA
      concentrations were associated with lower AFC, raising concern for possible
      accelerated follicle loss and reproductive aging. 

PMID- 24100208
TI  - Antimicrobial resistant Escherichia coli in the municipal wastewater system:
      effect of hospital effluent and environmental fate.
AB  - The prevalence of antimicrobial resistant (AMR) bacteria is increasing worldwide
      and remains a significant medical challenge which may lead to antimicrobial
      redundancy. The contribution of hospital effluent to the prevalence of resistance
      in wastewater treatment plant (WWTP) effluents is not fully understood. AMR
      bacteria contained in hospital effluent may be released into the aquatic and soil
      environments after WWTP processing. Hence, the objective of this study is to
      identify the extent hospital effluent contributes to contamination of these
      environments by comparing two WWTPs, one which receives hospital effluent and one
      which does not. AMR Escherichia coli were monitored in the two WWTPs. A model was
      developed using these monitored values to predict the effect of hospital effluent
      within a WWTP. The model predicted levels of AMR E. coli in the aquatic
      environment and potential bather exposure to AMR E. coli. The model results were
      highly variable. WWTP influent containing hospital effluent had a higher mean
      percentage of AMR E. coli; although, there appeared to be no within treatment
      plant effect on the prevalence of AMR E. coli. Examination of WWTP sludge showed
      a similar variation. There appeared to be no consistent effect from the presence
      of hospital effluent. The human exposure assessment model predicted swimmer
      intake of AMR E. coli between 6 and 193CFU/100ml sea water. It appears that
      hospital effluent is not the main contributing factor behind the development and
      persistence of AMR E. coli within WWTPs, although resistance may be too well
      developed to identify an influence from hospital effluent. Mitigation needs to
      focus on the removal of already present resistant bacteria but for new or
      hospital specific antimicrobials focus needs to be on their limited release
      within effluents or separate treatment. 

PMID- 24100210
TI  - Lattice charge models and core level shifts in disordered alloys.
AB  - Differences in core level binding energies between atoms belonging to the same
      chemical species can be related to differences in their intra- and extra-atomic
      charge distributions, and differences in how their core holes are screened. With
      this in mind, we consider the charge-excess functional model (CEFM) for net
      atomic charges in alloys (Bruno et al 2003 Phys. Rev. Lett. 91 166401). We begin
      by deriving the CEFM energy function in order to elucidate the approximations
      which underpin this model. We thereafter consider the particular case of the CEFM
      in which the strengths of the 'local interactions' within all atoms are the same.
      We show that for binary alloys the ground state charges of this model can be
      expressed in terms of charge transfer between all pairs of unlike atoms
      analogously to the linear charge model (Magri et al 1990 Phys. Rev. B 42 11388).
      Hence, the model considered is a generalization of the linear charge model for
      alloys containing more than two chemical species. We then determine the model's
      unknown 'geometric factors' over a wide range of parameter space. These
      quantities are linked to the nature of charge screening in the model, and we
      illustrate that the screening becomes increasingly universal as the strength of
      the local interactions is increased. We then use the model to derive analytical
      expressions for various physical quantities, including the Madelung energy and
      the disorder broadening in the core level binding energies. These expressions are
      applied to ternary random alloys, for which it is shown that the Madelung energy
      and magnitude of disorder broadening are maximized at the composition at which
      the two species with the largest 'electronegativity difference' are equal, while
      the remaining species have a vanishing concentration. This result is somewhat
      counterintuitive with regards to the disorder broadening since it does not
      correspond to the composition with the highest entropy. Finally, the model is
      applied to CuPd and CuZn random alloys. The model is used to deduce the effective
      radii associated with valence electron charge transfer for Cu, Pd and Zn in these
      systems for use in the 'ESCA potential model' of x-ray photoelectron
      spectroscopy. The effective radii are found to be R1/3, where R1 is the nearest
      neighbor distance, with only small variations between chemical elements and
      between different systems. The model provides a framework for rationalizing the
      disorder broadenings in these systems: they can be understood in terms of an
      interplay between the broadening in the Madelung potentials and the broadening in
      the intra-atomic electrostatic potentials.

PMID- 24100209
TI  - Trip to ER: MicroRNA-mediated translational repression in plants.
AB  - miRNAs elicit gene silencing at the post-transcriptional level by several modes
      of action: translational repression, mRNA decay, and mRNA cleavage. Studies in
      animals have suggested that translational repression occurs at early steps of
      translation initiation, which can be followed by deadenylation and mRNA decay.
      Plant miRNAs were originally thought to solely participate in mRNA cleavage, but
      increasing evidence has indicated that they are also commonly involved in
      translational inhibition. Here we discuss recent findings on miRNA-mediated
      translational repression in plants. The identification of AMP1 in Arabidopsis as
      a protein required for the translational repression but not the mRNA cleavage
      activity of miRNAs links miRNA-based translational repression to the endoplasmic
      reticulum (ER). Future work is required to further elucidate the miRNA machinery
      on the ER. 

PMID- 24100211
TI  - Employment of colorimetric enzyme assay for monitoring expression and solubility
      of GST fusion proteins targeted to inclusion bodies.
AB  - High levels of recombinant protein expression can lead to the formation of
      insoluble inclusion bodies. These complex aggregates are commonly solubilized in
      strong denaturants, such as 6-8M urea, although, if possible, solubilization
      under milder conditions could facilitate subsequent refolding and purification of
      bioactive proteins. Commercially available GST-tag assays are designed for
      quantitative measurement of GST activity under native conditions. GST fusion
      proteins accumulated in inclusion bodies are considered to be undetectable by
      such assays. In this work, solubilization of recombinantly produced proteins was
      performed in 4M urea. The activity of rGST was assayed in 2M urea and it was
      shown that rGST preserves 85% of its activity under such denaturing conditions. A
      colorimetric GST activity assay with 1-chloro-2, 4-dinitrobenzene (CDNB) was
      examined for use in rapid detection of expression targeted to inclusion bodies
      and for the identification of inclusion body proteins which can be solubilized in
      low concentrations of chaotropic agents. Applicability of the assay was evaluated
      by tracking protein expression of two GST-fused allergens of biopharmaceutical
      value in E. coli, GST-Der p 2 and GST-Mus a 5, both targeted to inclusion bodies.

PMID- 24100212
TI  - STAT3 regulates uterine epithelial remodeling and epithelial-stromal crosstalk
      during implantation.
AB  - Embryo implantation is regulated by a variety of endometrial factors, including
      cytokines, growth factors, and transcription factors. Earlier studies identified
      the leukemia inhibitory factor (LIF), a cytokine produced by uterine glands, as
      an essential regulator of implantation. LIF, acting via its cell surface
      receptor, activates the signal transducer and activator of transcription 3
      (STAT3) in the uterine epithelial cells. However, the precise mechanism via which
      activated STAT3 promotes uterine function during implantation remains unknown. To
      identify the molecular pathways regulated by STAT3, we created SW(d/d) mice in
      which Stat3 gene is conditionally inactivated in uterine epithelium. The SW(d/d)
      mice are infertile due to a lack of embryo attachment to the uterine luminal
      epithelium and consequent implantation failure. Gene expression profiling of
      uterine epithelial cells of SW(d/d) mice revealed dysregulated expression of
      specific components of junctional complexes, including E-cadherin, alpha- and
      beta-catenin, and several claudins, which critically regulate epithelial
      junctional integrity and embryo attachment. In addition, uteri of SW(d/d) mice
      exhibited markedly reduced stromal proliferation and differentiation, indicating
      that epithelial STAT3 controls stromal function via a paracrine mechanism. The
      stromal defect arose from a drastic reduction in the production of several
      members of the epidermal growth factor family in luminal epithelium of SW(d/d)
      uteri and the resulting lack of activation of epidermal growth factor receptor
      signaling and mitotic activity in the stromal cells. Collectively, our results
      uncovered an intricate molecular network operating downstream of STAT3 that
      regulates uterine epithelial junctional reorganization, and stromal
      proliferation, and differentiation, which are critical determinants of successful
      implantation. 

PMID- 24100214
TI  - Renal sympathetic nerve ablation for the management of resistant hypertension: an
      update.
AB  - PURPOSE OF REVIEW: The aim is to provide clinicians with a concise update on
      renal sympathetic nerve ablation in the management of resistant hypertension. The
      review will specifically discuss the latest clinical trial findings,
      technological advancements in ablation modalities and expert guidelines for
      patient eligibility. Novel therapeutic applications beyond blood pressure (BP)
      control will also be discussed. RECENT FINDINGS: Follow-up data from the
      Symplicity Clinical Trials Program provides further evidence for the safety of
      the procedure and substantiates a sustained reduction in BP in most patients with
      resistant hypertension. Recently published expert consensus statements recommend
      that only patients with resistant hypertension should undergo the procedure at
      this stage. Several alternative treatment modalities for renal denervation have
      been developed to improve efficacy, procedure time and safety. Initial findings
      suggest comparable BP reductions amongst technical approaches. Several pilot
      studies, although predominantly uncontrolled, indicate additional benefits of
      renal sympathetic nerve ablation on regression of hypertensive end-organ damage,
      heart failure, cardiac arrhythmias and other disturbances commonly associated
      with resistant hypertension. SUMMARY: Catheter-based renal nerve ablation is
      emerging as a well tolerated, effective and cost-effective treatment to control
      BP in patients with resistant hypertension. Further studies are required to
      determine the long-term impact of this novel therapeutic option.

PMID- 24100213
TI  - Cell-specific actions of a human LHX3 gene enhancer during pituitary and spinal
      cord development.
AB  - The LIM class of homeodomain protein 3 (LHX3) transcription factor is essential
      for pituitary gland and nervous system development in mammals. In humans,
      mutations in the LHX3 gene underlie complex pediatric syndromes featuring
      deficits in anterior pituitary hormones and defects in the nervous system. The
      mechanisms that control temporal and spatial expression of the LHX3 gene are
      poorly understood. The proximal promoters of the human LHX3 gene are insufficient
      to guide expression in vivo and downstream elements including a conserved
      enhancer region appear to play a role in tissue-specific expression in the
      pituitary and nervous system. Here we characterized the activity of this
      downstream enhancer region in regulating gene expression at the cellular level
      during development. Human LHX3 enhancer-driven Cre reporter transgenic mice were
      generated to facilitate studies of enhancer actions. The downstream LHX3 enhancer
      primarily guides gene transcription in alpha-glycoprotein subunit -expressing
      cells secreting the TSHbeta, LHbeta, or FSHbeta hormones and expressing the GATA2
      and steroidogenic factor 1 transcription factors. In the developing nervous
      system, the enhancer serves as a targeting module active in V2a interneurons.
      These results demonstrate that the downstream LHX3 enhancer is important in
      specific endocrine and neural cell types but also indicate that additional
      regulatory elements are likely involved in LHX3 gene expression. Furthermore,
      these studies revealed significant gonadotrope cell heterogeneity during
      pituitary development, providing insights into the cellular physiology of this
      key reproductive regulatory cell. The human LHX3 enhancer-driven Cre reporter
      transgenic mice also provide a valuable tool for further developmental studies of
      cell determination and differentiation in the pituitary and nervous system. 

PMID- 24100215
TI  - The association of physical activity and physical function with clinical outcomes
      in adults with chronic kidney disease.
AB  - PURPOSE OF REVIEW: Despite guidelines supporting the regular assessment of
      physical functioning and encouragement of physical activity in management of the
      patient with chronic kidney disease (CKD), implementation has been undermined by
      a lack of understanding of the evidence for this recommendation. The purpose of
      this review is to present a summary of emerging data from larger epidemiologic
      cohorts that report associations between low levels of physical functioning
      and/or low physical activity and clinical outcomes in patients with CKD. RECENT
      FINDINGS: Low levels of physical activity and poor physical functioning are
      strongly associated with mortality and poor clinical outcomes in adult patients
      with CKD, regardless of treatment modality. Low physical performance and activity
      limitations are more prevalent in patients with CKD, regardless of age, compared
      to older community-dwelling adults. SUMMARY: The strength of the evidence
      presented should strongly motivate a focus of treatment on assessing and
      improving physical activity and physical function as part of routine patient
      centered management of persons with CKD. Physical activity interventions are
      warranted because patients with CKD, regardless of age, have a high prevalence of
      low physical functioning and frailty that is similar to or higher than the
      general population of elderly adults; physical activity, physical function, and
      performance are strongly associated with all-cause mortality; and exercise
      training and exercise counseling have been shown to improve measures of physical
      functioning.

PMID- 24100216
TI  - Anticoagulant and antiplatelet therapy in patients with chronic kidney disease:
      risks versus benefits review.
AB  - PURPOSE OF REVIEW: Atrial fibrillation and cardiovascular death are increased in
      end-stage renal disease (ESRD) patients compared to the general population. The
      effect of anticoagulant and antiplatelet medications for these indications in
      ESRD is unclear. However, both classes of medications have been used for the
      preservation of vascular access. This review explores the risks and benefits of
      anticoagulant and antiplatelet medications in ESRD. RECENT FINDINGS: ESRD
      patients with atrial fibrillation have a two and three-fold greater risk of death
      and stroke, respectively, than ESRD patients without atrial fibrillation.
      Warfarin does not appear to decrease this risk, and increases the risk of
      bleeding and vascular calcification. Warfarin also does not appear to be
      effective for vascular access preservation. In a few large observational studies,
      antiplatelet agents did not decrease the risk of cardiovascular death, but
      confounding by indication is likely. Antiplatelet agents do appear to prolong
      unassisted arteriovenous graft patency, but the effect is modest. SUMMARY: The
      role of anticoagulant and antiplatelet agents for atrial fibrillation and
      cardiovascular disease in ESRD remains unclear. Well designed randomized
      controlled trials to determine the role of anticoagulation in ESRD patients with
      atrial fibrillation, and anticoagulant and antiplatelet medications in the
      preservation of central venous catheter function are required.

PMID- 24100217
TI  - Electronic alerts for acute kidney injury.
AB  - PURPOSE OF REVIEW: Acute kidney injury (AKI) is extremely common in hospitalized
      patients and its presence infers a poorer chance of survival, longer hospital
      stays and an increased risk of subsequent chronic kidney disease. Recent reports
      have suggested that standards of care for patients with AKI are often suboptimal
      and that this contributes to poor outcomes. In an attempt to address delays in
      diagnosing AKI, there has been increasing interest in e-alert systems for AKI.
      This review aims to discuss recent developments in e-alert methodologies, as well
      as examining the evidence to support their effectiveness. RECENT FINDINGS:
      Several e-alert systems for AKI have been reported, including more recent
      descriptions of hospital-wide systems that apply current diagnostic criteria and
      run sustainably in routine clinical practice. Evidence is accumulating to show
      their impact in altering physician behaviour and triggering earlier intervention.
      Emerging data suggest that in combination with other service improvement
      strategies, this may translate into improved patient outcomes. SUMMARY: The
      current ad-hoc development of e-alert systems needs to be addressed by arriving
      at consensus around the way in which these systems should apply diagnostic
      criteria, particularly with respect to selection of baseline creatinine value.
      Enhancements in IT provision may provide the only durable solution to this, while
      at the same time facilitating wider uptake. Wider use will allow for further
      study of the value of e-alerts, including their use in other settings such as
      primary care.

PMID- 24100219
TI  - Pros and cons of catheter lock solutions.
AB  - PURPOSE OF REVIEW: Catheter-related bacteremia (CRB) and catheter dysfunction are
      major sources of morbidity and mortality when central venous catheters are used
      as long-term vascular access in hemodialysis patients. Attempts have been made to
      minimize these complications by the prophylactic use of catheter locking
      solutions. This review aims to describe the recent advances in the field of lock
      solutions and to discuss the benefits and risks associated with the routine use
      of antimicrobial and/or antithrombotic lock solutions. RECENT FINDINGS:
      Antithrombotic lock solutions may improve patency and CRB but may be cost
      prohibitive. Antimicrobial lock solutions may decrease the incidence of CRB, but
      their routine use is concerning for the risk of systemic toxicity and the
      development of resistant organisms. Preliminary results suggest a novel
      antimicrobial and antithrombotic lock solution may be promising in maintaining
      patency, while decreasing catheter-related bacteremia. SUMMARY: The ideal
      catheter lock solution would be one that prevents infections and thrombosis
      safely and effectively, while being economically viable. Recent developments have
      led to improvements in the development of catheter locking solutions, but the
      search for the perfect 'solution' is still ongoing.

PMID- 24100218
TI  - What have we learned about chronic kidney disease-mineral bone disorder from the
      EVOLVE and PRIMO trials?
AB  - PURPOSE OF REVIEW: The treatment of chronic kidney disease-mineral bone disorder
      (CKD-MBD) has traditionally focused on improvement in biochemical parameters of
      the disease. However, studies evaluating hard clinical end points or surrogate
      end points are limited. RECENT FINDINGS: Two randomized controlled trials have
      recently been published. In the EVOLVE study (Evaluation of Cinacalcet
      Hydrochloride Therapy to Lower Cardiovascular Events), cinacalcet was compared
      with placebo in 3883 haemodialysis patients with secondary hyperparathyroidism.
      The primary end point (death, myocardial infarction, unstable angina, heart
      failure or peripheral vascular disease) in an unadjusted intention-to-treat
      analysis was not significant [hazard ratio 0.93; 95% confidence interval (CI)
      0.85-1.02, P=0.11]. However, the pre-specified secondary end points of an
      adjusted intention-to-treat analysis (hazard ratio 0.88; 95% CI 0.79-0.97,
      P=0.008) were significant. In the PRIMO (Paricalcitol Capsule Benefits in Renal
      Failure Induced Cardiac Morbidity) trial, 227 patients with CKD stage 3-4 and
      left ventricular hypertrophy by echocardiography were randomized to paricalcitol
      or placebo. The primary end point of change in left ventricular mass index by MRI
      after 12 months was not different between the two groups, but the prespecified
      end point of cardiovascular-related hospitalizations was reduced in the
      paricalcitol-treated group (P=0.04). SUMMARY: The results of these two randomized
      controlled trials have negative primary end points but significant secondary end
      points and thus require physicians to individualize therapies for the treatment
      of secondary hyperparathyroidism.

PMID- 24100220
TI  - Improving outcomes by changing hemodialysis practice patterns.
AB  - PURPOSE OF REVIEW: This review examines recent advances in understanding of how
      clinical outcomes for hemodialysis patients may be improved by achieving longer
      or more frequent treatment times, lower ultrafiltration rates (UFRs), improving
      nutritional status, and individualizing dialysate composition. This review also
      discusses the controversy related to timing of dialysis initiation. RECENT
      FINDINGS: Many observational studies and several randomized controlled trials
      indicate longer dialysis treatment times, particularly nocturnal dialysis, and/or
      more frequent dialysis improve morbidity and mortality. Recent evidence also
      suggests that lower UFR and more consistent achievement of 'dry weight' may help
      minimize the damage from myocardial stunning and chronic volume overload that
      occurs in the majority of patients who receive conventional hemodialysis during
      the day with a standard schedule of 3-5 h, 3 times a week. Other aspects of the
      dialysis procedure such as appropriate estimated glomerular filtration rate for
      dialysis initiation and individualizing dialysate composition may also minimize
      cardiovascular risk. Finally, several studies have highlighted the benefits of
      oral nutritional supplementation (ONS) during dialysis. SUMMARY: Greater
      treatment times per week with slower UFR, consistent attainment of 'dry weight',
      individualized dialysate prescriptions, and administration of ONS to malnourished
      patients are likely to reduce hospitalizations and improve survival in this high
      risk population of end-stage renal disease patients.

PMID- 24100221
TI  - Beyond calcineurin inhibitors: emerging agents in kidney transplantation.
AB  - PURPOSE OF REVIEW: Despite their effectiveness, calcineurin inhibitors (CNIs)
      represent a major obstacle in the improvement of long-term graft survival in
      transplantation. The identification of new agents to implement CNI-free regimens
      is the focus of current transplant research. The purpose of this review is to
      summarize the novel immunosuppressive agents, including details about their
      mechanisms of action, stages of development, potential benefits and challenges.
      RECENT FINDINGS: Targeting costimulation with belatacept is now an option for
      controlling the alloimmune response and has proved to be more effective in
      preserving long-term allograft function than CNIs despite an increased rate of
      acute rejection in some studies. mTOR inhibitors are also promising with their
      remarkable antineoplastic properties, though frequent side-effects may limit
      their broader use. Other agents under development include JAK inhibitors, CD40
      blockade and leukocyte adhesion blockers, with unique potential benefits and side
      effects in transplantation. SUMMARY: Novel immunosuppressive agents are now
      available for use in CNI-free regimens in solid organ transplantation. Timing of
      initiation as well as long-term efficacy and safety are questions that remain to
      be answered in future clinical trials.

PMID- 24100222
TI  - Corin: a new player in the regulation of salt-water balance and blood pressure.
AB  - PURPOSE OF REVIEW: Natriuretic peptides play a key role in regulation of blood
      pressure and volume homeostasis due to their natriuretic/diuretic and
      vasodilatory actions. The natriuretic and diuretic responses to natriuretic
      peptides are markedly attenuated in edematous disease states. Our goal is to
      review the mechanisms underlying this phenomenon, with special emphasis on the
      role of corin in salt retention and edema formation in heart failure and
      nephrotic syndrome, and pathogenesis of hypertension. RECENT FINDINGS: Although
      three decades have passed since the discovery of atrial natriuretic peptide
      (ANP), major advances in understanding the physiological and pathophysiological
      role of the natriuretic peptide family in the regulation of sodium (Na) and water
      balance are still emerging. As well as ANP, the natriuretic peptide family
      contains at least two other members: brain natriuretic peptide (BNP) and C-type
      natriuretic peptide (CNP). Although encoded by different genes, these natriuretic
      peptides share a high similarity in their chemical structure and biosynthesis
      pathway. ANP and BNP are produced from proANP and proBNP, respectively, which are
      converted into the active forms mainly by corin. The latter is a transmembrane
      serine protease localized to the heart, and to a lesser extent to the kidneys.
      Recent studies have demonstrated that perturbations in corin activity lead to
      elevation of the prohormones at the expense of the mature forms, thereby causing
      the development of salt-sensitive hypertension, preeclampsia, cardiac
      hypertrophy, and Na and water retention. SUMMARY: Natriuretic peptides are an
      important endocrine system in the regulation of body fluid balance and blood
      pressure. Corin mediates an essential step in the cascade of natriuretic peptide
      biosynthesis and eventually their action. Thus, it is postulated that aberrations
      in the normal activity of corin may contribute to cardiovascular and renal
      diseases.

PMID- 24100223
TI  - The effect of perinatal exposures on the infant: antidepressants and depression.
AB  - Depression, anxiety, or both, during pregnancy are common complications during
      the perinatal period, with 15-20% of women experiencing depression at some point
      during their pregnancy. Considerable evidence suggests that untreated or
      undertreated maternal Axis I mood disorders can increase the risk for preterm
      birth, low birth weight, and alter neurobehavioral development in utero.
      Serotonin reuptake inhibitor antidepressants are often considered for antenatal
      therapy, with the goal of improving maternal mental health during pregnancy.
      Treatment with a serotonin-reuptake inhibitor, however, does not guarantee
      remission of depression, and in-utero serotonin reuptake inhibitor exposure has
      also been linked to increased risks for adverse infant outcomes. In this chapter,
      evidence linking serotonin reuptake inhibitor use with an increased risk for
      postnatal adaptation syndrome, congenital heart defects, and neonatal persistent
      pulmonary hypertension is reviewed. Management decisions should include attention
      to the continuum of depression symptoms, from subclinical to severe major
      depressive disorder and the long-term developmental risks that might also be
      associated with pre- and postnatal exposure. 

PMID- 24100224
TI  - Degeneration of a CRISPR/Cas system and its regulatory target during the
      evolution of a pathogen.
AB  - CRISPR/Cas systems are bacterial RNA-guided endonuclease machineries that target
      foreign nucleic acids. Recently, we demonstrated that the Cas protein Cas9
      controls gene expression and virulence in Francisella novicida by altering the
      stability of the mRNA for an immunostimulatory bacterial lipoprotein (BLP).
      Genomic analyses, however, revealed that Francisella species with increased
      virulence harbor degenerated CRISPR/Cas systems. We hypothesize that CRISPR/Cas
      degeneration removed a barrier against genome alterations, which resulted in
      enhanced virulence. Importantly, the BLP locus was also lost; likely a necessary
      adaptation in the absence of Cas9-mediated repression. CRISPR/Cas systems likely
      play regulatory roles in numerous bacteria, and these data suggest additional
      genomic changes may be required to maintain fitness after CRISPR/Cas loss in such
      bacteria, having important evolutionary implications. 

PMID- 24100225
TI  - Structural and mechanistic insights into the arginine/lysine-rich peptide motifs
      that interact with P97/VCP.
AB  - P97 protein, also referred to as valosin-containing protein (VCP), is an AAA
      ATPase (ATPase associated with a variety of cellular activities) that mediates
      vital cellular activities with the cooperation of many cofactors. A group of
      cofactors interact with the N-terminal domain of P97 (P97N) through their Arg/Lys
      rich peptide motifs. We investigated the interactions between P97 and these
      motifs, including VCP-binding motif (VBM) and VCP-interacting motif (VIM). The
      solution structures of the VBM motif from HRD1 and the VIM motif from SVIP are
      both comprised mainly of a single alpha-helix. The VIM motifs generally have
      stronger P97N-binding affinities than the VBMs, and SVIP (VIM) can compete with
      HRD1-VBM for the interaction, providing a possibility that VIM-containing
      proteins (such as SVIP) act as competitors against VBM-containing proteins (such
      as HRD1) for interacting with P97. Based on biochemical features of the VBM
      motifs, we also identified NUB1L (NEDD8 ultimate buster-1 long) as a novel VBM
      containing protein, which is involved in proteasomal degradation of NEDD8 through
      the P97 pathway. 

PMID- 24100226
TI  - Biochemical properties of nematode O-acetylserine(thiol)lyase paralogs imply
      their distinct roles in hydrogen sulfide homeostasis.
AB  - O-Acetylserine(thiol)lyases (OAS-TLs) play a pivotal role in a sulfur
      assimilation pathway incorporating sulfide into amino acids in microorganisms and
      plants, however, these enzymes have not been found in the animal kingdom.
      Interestingly, the genome of the roundworm Caenorhabditis elegans contains three
      expressed genes predicted to encode OAS-TL orthologs (cysl-1-cysl-3), and a
      related pseudogene (cysl-4); these genes play different roles in resistance to
      hypoxia, hydrogen sulfide and cyanide. To get an insight into the underlying
      molecular mechanisms we purified the three recombinant worm OAS-TL proteins, and
      we determined their enzymatic activities, substrate binding affinities,
      quaternary structures and the conformations of their active site shapes. We show
      that the nematode OAS-TL orthologs can bind O-acetylserine and catalyze the
      canonical reaction although this ligand may more likely serve as a competitive
      inhibitor to natural substrates instead of being a substrate for sulfur
      assimilation. In addition, we propose that S-sulfocysteine may be a novel
      endogenous substrate for these proteins. However, we observed that the three OAS
      TL proteins are conformationally different and exhibit distinct substrate
      specificity. Based on the available evidences we propose the following model:
      CYSL-1 interacts with EGL-9 and activates HIF-1 that upregulates expression of
      genes detoxifying sulfide and cyanide, the CYSL-2 acts as a cyanoalanine synthase
      in the cyanide detoxification pathway and simultaneously produces hydrogen
      sulfide, while the role of CYSL-3 remains unclear although it exhibits
      sulfhydrylase activity in vitro. All these data indicate that C. elegans OAS-TL
      paralogs have distinct cellular functions and may play different roles in
      maintaining hydrogen sulfide homeostasis. 

PMID- 24100227
TI  - Acute pyelonephritis in pregnancy: an 18-year retrospective analysis.
AB  - OBJECTIVE: We sought to describe the incidence of acute pyelonephritis in
      pregnancy, and to assess its association with perinatal outcomes in an integrated
      health care system. STUDY DESIGN: A retrospective cohort study was performed
      using medical records on 546,092 singleton pregnancies delivered in all Kaiser
      Permanente Southern California hospitals from 1993 through 2010. These medical
      records include the perinatal service system along with inpatient and outpatient
      encounter files. Adjusted odd ratios (ORs) and 95% confidence intervals (CIs)
      were used to estimate associations. RESULTS: The incidence of acute antepartum
      pyelonephritis was 0.5% (2894/543,430). Women with pyelonephritis in pregnancy
      were more likely to be black or Hispanic, young, less educated, nulliparous,
      initiate prenatal care late, and smoke during pregnancy. Pregnancies of women
      with pyelonephritis compared to those without were more likely to be complicated
      by anemia (26.3% vs 11.4%; OR, 2.6; 95% CI, 2.4-2.9), septicemia (1.9% vs 0.03%;
      OR, 56.5; 95% CI, 41.3-77.4), acute pulmonary insufficiency (0.5% vs 0.04%; OR,
      12.5; 95% CI, 7.2-21.6), acute renal dysfunction (0.4% vs 0.03%; OR, 16.5; 95%
      CI, 8.8-30.7), and spontaneous preterm birth (10.3% vs 7.9%; OR, 1.3; 95% CI, 1.2
      1.5). Most of the preterm births occurred between 33-36 weeks (9.1%). CONCLUSION:
      We characterize the incidence of pyelonephritis in an integrated health care
      system where routine prenatal screening for asymptomatic bacteriuria is employed.
      Maternal complications are commonly encountered and the risk of preterm birth is
      higher than the baseline obstetric population.

PMID- 24100228
TI  - Rapid emergence of secondary resistance to gentamicin and colistin following
      selective digestive decontamination in patients with KPC-2-producing Klebsiella
      pneumoniae: a single-centre experience.
AB  - After a single patient was transferred to Leipzig University Hospital from a
      hospital in Rhodes, Greece, the hospital experienced the largest outbreak due to
      a KPC-2-producing Klebsiella pneumoniae (KPC-2-KP) strain thus far observed in
      Germany. Ninety patients hospitalised between July 2010 and October 2012 were
      affected. In an attempt to eliminate KPC-2-KP from their digestive tracts, 14
      consecutive patients (16%) were treated with a short course (7 days) of selective
      digestive decontamination (SDD), employing colistin (1 million units q.i.d.) and
      gentamicin (80 mg q.i.d.) as oral solutions, and applying colistin/gentamicin gel
      (0.5 g) to the oral cavity. In a retrospective analysis, these 14 SDD patients
      were compared with the remaining 76 patients harbouring KPC-2-KP. KPC-2-KP
      carrier status was followed in all 14 SDD patients by submitting stool samples to
      KPC-specific PCR. The mean follow-up period was 48 days (range 12-103 days).
      Successful elimination of KPC-2-KP was defined as a minimum of three consecutive
      negative PCR test results separated by >=48 h each. Decolonisation of KPC-2-KP
      was achieved in 6/14 patients (43%) after a mean of 21 days (range 12-40 days),
      but was also observed in 23/76 (30%) of the non-SDD controls (P = 0.102). SDD
      treatment resulted in the development of secondary resistance to colistin (19%
      increase in resistance rate) and gentamicin (45% increase) in post-treatment
      isolates. In the control group, no secondary resistance occurred. We conclude
      that the SDD protocol applied in this study was not sufficiently effective for
      decolonisation and was associated with resistance development.

PMID- 24100229
TI  - Weak localization and Mott state in two-dimensional Sr3V5S11.
AB  - We report on the high-pressure synthesis, structural study and physical
      properties of a new layered compound, Sr3V5S11. Single-crystals of ~0.3 mm size
      were synthesized at the optimized growth conditions of 6 GPa and 1600  degrees 
      C. The refinement of x-ray diffraction data indicates that the crystal structure
      is monoclinic (space group C2/c), with cell parameters a = 8.7165(7) A, b =
      15.1096(13) A, c = 23.111(2) A, and beta = 98.734(9). The structure consists of a
      stacking of VS2 layers with a CdI2-type structure within the ab-plane connected
      by trimers of face-sharing VS6 octahedra oriented along the out-of-plane
      direction. Salient features are a 4 + valence of the V ions in the planes and a 3
      + valence in the trimers and a large stripe-like modulation of the V-V distances
      in the planes leading to quasi-one-dimensional properties. The magnetic
      susceptibility displays a large temperature-independent contribution, chi0, in
      addition to a moderate Curie-Weiss term. In the 300-120 K range, the electrical
      resistivity is described well by a semiconducting-like behaviour with a room
      temperature value of ~1.2-10 mOmega cm and a modest activation energy of ~13.5
      meV. At lower temperatures, a crossover to a one-dimensional variable range
      hopping regime is observed, supporting a scenario of a correlated 1D system.

PMID- 24100230
TI  - Evidence mounts that red cells and deoxyhemoglobin can reduce nitrite to
      bioactive NO to mediate intravascular endocrine NO signaling: commentary on "Anti
      platelet effects of dietary nitrate in healthy volunteers: involvement of cGMP
      and influence of sex".

PMID- 24100231
TI  - When hypoglycemia is not obvious: diagnosing and treating under-recognized and
      undisclosed hypoglycemia.
AB  - Hypoglycemia continues to be a significant problem for patients with diabetes.
      The incidence remains high but patients may also be under-reporting hypoglycemic
      events for various reasons, including hypoglycemia unawareness and deliberate non
      reporting. This restricts the ability of healthcare professionals to manage
      treatment effectively. The aim of this article is to focus specifically on the
      issues associated with hypoglycemia unawareness and undisclosed hypoglycemia. The
      article provides general practice teams with an overview of these problems and,
      through patient narratives, suggests ways to mitigate them. 

PMID- 24100232
TI  - Dufour's gland secretion, sterility and foraging behavior: correlated behavior
      traits in bumblebee workers.
AB  - Bombus terrestris colonies go through two major phases: the "pre-competition
      phase" in which the queen is the sole reproducer and aggression is rare, and the
      "competition phase" in which workers aggressively compete over reproduction.
      Conflicts over reproduction are partially regulated by a group of octyl esters
      that are produced in Dufour's gland of reproductively subordinate workers and
      protect them from being aggressed. However, workers possess octyl esters even
      before overt aggression occurs, raising the question of why produce the ester
      signal before it is functionally necessary? In most insect societies, foragers
      show reduced aggression and low dominance rank. We hypothesize that ester
      production in B. terrestris is not only correlated with sterility but also with
      foraging, signaling cooperative behavior by subordinate workers. Such a signal
      helps to maintain social organization, reduce the cost of fights between
      reproductives and helpers, and increase colony productivity, enabling
      subordinates to gain greater inclusive fitness. We demonstrate that foragers
      produce larger amounts of esters compared to non-foragers, and that their amounts
      positively correlate with foraging efforts. We further suggest that task
      performance, potential fecundity, and aggression are interlinked, and that worker
      worker interactions are involved in regulating foraging behavior. B. terrestris,
      being an intermediate phase between primitive and derived eusocial insects,
      provides an excellent model for understanding the evolution of early phases of
      eusociality. Our results, combined with those in primitively eusocial wasps,
      suggest that at early stages of social evolution, reproduction was regulated by a
      "primordial division of labor", that comprised foragers and reproducers, which
      further evolved to a more complex division of labor, a hallmark of eusociality. 

PMID- 24100233
TI  - Single-cell chemiluminescence imaging of parvovirus B19 life cycle.
AB  - Human parvovirus B19 (B19V) is a single-stranded DNA virus. The genome encodes a
      multifunctional non-structural protein (NS), two capsid proteins (VP1, VP2) and
      other small non-structural proteins (7.5 kDa, 9 kDa, 11 kDa). Within sensitive
      cells, B19V can achieve a productive replicative cycle or, on the contrary,
      establish persistence; differences in its expression profile have been yet
      investigated following in vitro infections by methodologies enabling information
      on the entire infected cell population. Conversely, the present study reports
      quantitative data on the production of B19V analytes (DNA, RNAs, and proteins) at
      single cell-level, underlining cell-to-cell differences through the viral
      specific macromolecular synthesis process. Microscope imaging assays (in situ
      hybridization and immunocytochemical assays), exploiting chemiluminescence as
      principle detection and targeting viral nucleic acids and antigens, have been
      performed on a permissive cell line following in vitro infection.
      Chemiluminescence, involving the emission of photons deriving from a chemical
      reaction, provided the localization and quantitative detection of analytes down
      to a few molecules within infected cells. In our experimental conditions, B19V
      transcriptional activity, leading to the production of NS and VP RNAs, has been
      detected early in the viral cycle (from 12h post-infection, hpi) and before
      genome replication, starting at 24 hpi. The analysis of VP RNAs and related
      proteins suggested an inhibitory effect on capsid protein translation, as a post
      transcriptional regulation events. Indeed, high levels of VP transcripts have
      been detected at early stages of infection while the proteins accumulated within
      cells only at 48-72 hpi.

PMID- 24100234
TI  - Interferon alpha/beta receptor knockout mice as a model to study bluetongue virus
      infection.
AB  - Bluetongue is an arthropod-borne disease caused by a virus of the genus
      Orbivirus, the bluetongue virus (BTV), which affects ruminant livestock such as
      cattle, sheep, and goats and wild ruminants such as deer, and camelids. Recently,
      adult mice with gene knockouts of the interferon alpha/beta receptor (IFNAR-/-)
      have been described as a model of lethal BTV infection. IFNAR(-/-) mice are
      highly susceptible to BTV-1, BTV-4 and BTV-8 infection when the virus is
      administered intravenously or subcutaneosuly. Disease progression and
      pathogenesis closely mimics signs of bluetongue disease in ruminants. In the
      present paper we review the studies where IFNAR(-/-) mice have been used as an
      animal model to study BTV transmission, pathogenesis, virulence, and protective
      efficacy of inactivated and new recombinant marker BTV vaccines. Furthermore, we
      report new data on protective efficacy of different strategies of BTV vaccination
      and also on induction of interferon alpha/beta and proinflammatory immune
      responses in IFNAR(-/-) mice infected with BTV. 

PMID- 24100236
TI  - Food mirages: geographic and economic barriers to healthful food access in
      Portland, Oregon.
AB  - This paper investigated the role of grocery store prices in structuring food
      access for low-income households in Portland, Oregon. We conducted a detailed
      healthful foods market basket survey and developed an index of store cost based
      on the USDA Thrifty Food Plan. Using this index, we estimated the difference in
      street-network distance between the nearest low-cost grocery store and the
      nearest grocery store irrespective of cost. Spatial regression of this metric in
      relation to income, poverty, and gentrification at the census tract scale lead to
      a new theory regarding food access in the urban landscape. Food deserts are
      sparse in Portland, but food mirages are abundant, particularly in gentrifying
      areas where poverty remains high. In a food mirage, grocery stores are plentiful
      but prices are beyond the means of low-income households, making them
      functionally equivalent to food deserts in that a long journey to obtain
      affordable, nutritious food is required in either case. Results suggested that
      evaluation of food environments should, at a minimum, consider both proximity and
      price in assessing healthy food access for low-income households. 

PMID- 24100235
TI  - Pseudovirus mimics cell entry and trafficking of the human polyomavirus JCPyV.
AB  - The normally asymptomatic human polyomavirus, JCPyV, is the causative agent of a
      rare but fatal demyelinating disease known as progressive multifocal
      leukoencephalopathy (PML). Individuals at risk for developing PML include those
      with AIDS, with other underlying immunosuppressive diseases, and in patients
      treated with immunomodulatory regimens. Drugs to prevent viral reactivation in
      the setting of immunosuppression or immunomodulation could be used to sustain
      lives. Development of such drugs has been impeded by the difficulty of growing
      and studying the virus. We sought to develop a more efficient method for
      screening drugs that inhibit viral infection. Pseudovirus models have been
      developed which may be of use in pharmaceutical research. The use of
      pseudoviruses as models for viral infection is dependent on them using similar
      pathways for infection as virus. We screened known inhibitors of viral entry for
      their ability to block pseudovirus infection. Here we show that the pseudovirus
      based on the human polyomavirus JCPyV recapitulates virus binding, entry and
      trafficking. This system can be used for high-throughput screening of antiviral
      drugs. 

PMID- 24100237
TI  - Walking together: the embodied and mobile production of a therapeutic landscape.
AB  - This paper draws on a case study of led group walks in the South-East of England
      to explore the affective potency of shared movement for producing therapeutic
      landscapes (landscapes that through placed practices become associated with
      health and healing). The paper addresses the lack of attention to embodiment and
      movement in work on therapeutic landscapes through an exploration of how shared
      movement can produce supportive social spaces that are experienced as
      restorative. Drawing on an expansive conception of mobility inspired by the
      'mobilities turn' in the social sciences in the last decade, the paper explores
      how the therapeutic landscape concept can be enriched by being approached through
      the lens of the body in movement. A complimentary concern in the paper is the
      ways in which supportive socialities and group dynamics are integral to many
      therapeutic landscape experiences. Walking together is found to have a
      significant impact on social interaction and together embodied mobilities and
      supportive socialities transform the countryside walkscape into a mobile
      therapeutic landscape and a site for shared therapeutic body work. 

PMID- 24100238
TI  - Do observed or perceived characteristics of the neighborhood environment mediate
      associations between neighborhood poverty and cumulative biological risk?
AB  - OBJECTIVE: To examine contributions of observed and perceived neighborhood
      characteristics in explaining associations between neighborhood poverty and
      cumulative biological risk (CBR) in an urban community. METHODS: Multilevel
      regression analyses were conducted using cross-sectional data from a probability
      sample survey (n=919), and observational and census data. Dependent variable:
      CBR. INDEPENDENT VARIABLES: neighborhood disorder, deterioration and
      characteristics; perceived neighborhood social environment, physical environment,
      and neighborhood environment. Covariates: neighborhood and individual
      demographics, health-related behaviors. RESULTS: Observed and perceived
      indicators of neighborhood conditions were significantly associated with CBR,
      after accounting for both neighborhood and individual level socioeconomic
      indicators. Observed and perceived neighborhood environmental conditions mediated
      associations between neighborhood poverty and CBR. CONCLUSIONS: Findings were
      consistent with the hypothesis that neighborhood conditions associated with
      economic divestment mediate associations between neighborhood poverty and CBR.

PMID- 24100240
TI  - State government organization of health services, 1990-2009: correlates and
      consequences.
AB  - OBJECTIVES: To describe changes in the organizational structure of state health
      related departments/agencies between 1990 and 2009; to identify factors
      associated with key organizational structures; and to investigate their
      relationship with different resource allocations across health policy areas, as
      represented by state budgets. DESIGN: Original data collection on the
      organization of state health-related departments/agencies from 1990 to 2009.
      Analyses included descriptive statistics, logistic regression, and time-series
      regression modeling. SETTING AND PARTICIPANTS: All 50 states. MAIN OUTCOMES
      MEASURES: Organizational structure of state government related to health in 4
      areas (Medicaid, public health, mental health, human services); coupling of
      Medicaid and public health in the same agency; state budget changes in health
      policy areas, including Medicaid, public health, and hospitals. RESULTS: The
      housing of 2 or more health-related functions in the same unit was common, with
      21 states combining public health and Medicaid at 1 or more points in time.
      Eighteen states (36%) reorganized their health agencies/departments during the
      study period. Controlling for numerous economic, social, and political factors,
      when the state agency responsible for public health is consolidated with
      Medicaid, the share of the state budget allocated to Medicaid declined
      significantly, while public health allocations were unchanged. However,
      consolidating Medicaid with other services did not impact state Medicaid
      spending. CONCLUSIONS: Government organizational structure related to health
      varies greatly across states and is somewhat dynamic. When Medicaid and public
      health functions are consolidated in the same stage agency, public health does
      not "lose" in terms of its share of the state budget. However, this could change
      as Medicaid costs continue to grow and with the implementation the Patient
      Protection and Affordable Care Act of 2010.

PMID- 24100239
TI  - Argonaute-3 activates the let-7a passenger strand microRNA.
AB  - MicroRNA duplices are separated into a guide and a passenger strand. By
      convention, the guide represents the active microRNA while the passenger is
      supposedly degraded. However, passenger strands also emerge as active microRNAs.
      It is unknown whether the guide-to-passenger-strand ratio can be actively
      regulated and which factors influence strand incorporation into the RISC. Here,
      we identify a microRNA with a variable guide-to-passenger-strand ratio along with
      its regulatory factor: Human Argonaute-3 specifically enhances the passenger
      strand expression and activity of the tumor suppressor microRNA let-7a. This post
      maturational effect is mediated by the Ago3 PAZ and MID domains yielding an
      elevated affinity for let-7a-3p. Notably, this is independent of the 5'-terminal
      basepair stability, challenging the universality of the respective rule for
      microRNA strand selection. Thus, this study uncovers the first protein regulator
      of the ratio between microRNA guide and passenger strand expression and activity.

PMID- 24100241
TI  - Continuing educational needs of APHA members within the professional public
      health workforce.
AB  - OBJECTIVE: To examine the continuing education needs of and method of course
      delivery for American Public Health Association (APHA) members. METHODS (DESIGN,
      SETTING, PARTICIPANTS): The APHA Education Board developed a list of 37 potential
      continuing education courses, 20 of which were linked to course competencies. An
      electronic survey of 22 104 APHA members was conducted to determine members'
      priorities. Survey data included age, gender, race/ethnicity, highest academic
      degree obtained, workplace setting, educational needs, and preferred method of
      course delivery. Data were primarily analyzed using descriptive statistics. MAIN
      OUTCOME MEASURES: Demographic data, educational needs, and preferred method of
      course delivery. RESULTS: Respondents numbered 5058, with 3836 (75.8%) interested
      in continuing education. For those indicating an interest, approximately 6 course
      areas per person were identified. A number of specific course areas were
      emphasized, including Leadership and Systems Thinking Skills and Policy
      Development and Program Planning. More than 50% of respondents favored obtaining
      courses using an online or computer-based format. Of the 24% uninterested in
      continuing education, 78% were in the age range of 25 to 65 years. CONCLUSIONS:
      Although this study identified continuing education needs of a wide cross section
      of APHA members, the response rate was low. Additional surveys should be
      conducted periodically to update course offerings and identify gaps in workforce
      training. Reasons for any disinterest in continuing education in public health
      should be explored.

PMID- 24100242
TI  - Public health grand rounds at the Centers for Disease Control and Prevention:
      evaluation feedback from a broad community of learners.
AB  - OBJECTIVE: To evaluate the relevance and educational benefit of monthly Public
      Health Grand Rounds (GR), an hour-long interactive lecture series featuring 1
      current, relevant public health topic. DESIGN: Quantitative and qualitative
      analysis of data evaluating GR format and content submitted by 2063 continuing
      education (CE) participants. SETTING: Survey data submitted electronically to the
      Centers for Disease Control and Prevention online CE system from January 2010
      through December 2011. PARTICIPANTS: Physicians, nurses, pharmacists, health
      education specialists, and other health care professionals seeking CE credits for
      Public Health GR. MAIN OUTCOME MEASURES: Proportion of respondents agreeing or
      strongly agreeing that GR is using educational strategies that enhance user
      learning and is meeting preidentified learning objectives. RESULTS: On questions
      involving instructional strategies and delivery methods, 95.0% and 95.6% of
      respondents, respectively, agreed or strongly agreed that the GR was conducive to
      learning. More than 90% of respondents agreed or strongly agreed that they could
      describe the burden of the disease/condition in question and identify key
      preventive interventions, knowledge gaps, and measures of public health progress.
      CONCLUSIONS: These evaluation results indicate that the GR is meeting content
      specific and educational needs of diverse health care professionals. The GR
      models organized scientific discussions on evidence and translation into real
      world impacts of decreased morbidity, mortality, and health care costs, and links
      public health to clinical practice. This promotes a greater understanding of the
      interplay of different health fields and may lead to greater and cross
      disciplinary collaborations.

PMID- 24100244
TI  - Infantile hypophosphatasia without bone deformities presenting with severe
      pyridoxine-resistant seizures.
AB  - An infant carrying a heterozygous c.43_46delACTA and a heterozygous c.668 G>A
      mutation in the ALPL gene with hypophosphatasia in the absence of bone
      deformities presented with therapy-resistant seizures. Pyridoxal phosphate was
      extremely high in CSF and plasma. Pyridoxine treatment had only a transient
      effect and the severe encephalopathy was fatal. Repeated brain MRIs showed
      progressive cerebral damage. The precise metabolic cause of the seizures remains
      unknown and pyridoxine treatment apparently does not cure the epilepsy. 

PMID- 24100243
TI  - High-dose enzyme replacement therapy in murine Hurler syndrome.
AB  - Mucopolysaccharidosis type I (MPS I) is an autosomal recessive disease that is
      systemic, including progressive neurodegeneration, mental retardation and death
      before the age of 10 years. MPS I results from deficiency of alpha-L-iduronidase
      (IDUA) in lysosomes and subsequent accumulation of glycosaminoglycans (GAG).
      Clinical enzyme replacement therapy (ERT) with intravenous laronidase reverses
      some aspects of MPS I disease (e.g., hepatomegaly, splenomegaly,
      glycosaminoglycanuria) and ameliorates others (e.g., pulmonary function, cardiac
      disease, arthropathy, exercise tolerance). However, neurologic benefits are
      thought to be negligible because the blood-brain barrier (BBB) blocks enzyme from
      reaching the central nervous system (CNS). We considered the possibility that a
      very high dose of intravenous laronidase might be able to traverse the BBB in
      small quantities, and provide some metabolic correction in the brain. To address
      this question, high-dose laronidase was administered (11.6 mg/kg, once per week,
      4 weeks) to adult MPS I mice. IDUA enzyme activity in the cortex of treated mice
      increased to 97% of that in wild type mice (p<0.01). GAG levels in cortex were
      reduced by 63% of that from untreated MPS I mice (p<0.05). Further,
      immunohistochemical analysis showed that treatment reduced secondary GM3
      ganglioside accumulation in treated MPS I mice. Water T-maze tests showed that
      the learning abnormality in MPS I mice was reduced (p<0.0001). In summary,
      repeated, high-dose ERT facilitated laronidase transit across the BBB, reduced
      GAG accumulation within the CNS, and rescued cognitive impairment.

PMID- 24100245
TI  - A silent nucleotide substitution in the ATP7A gene in a child with Menkes
      disease.
AB  - We present a case of classical Menkes disease (MD) due to a novel "silent"
      substitution in the ATP7A gene; c.2781G>A (p.K927K). The affected nucleotide is
      the last nucleotide in exon 13, and affects mRNA splicing. Transcripts missing
      exon 13; and transcripts missing exons 11, 12 and 13 in addition to a very small
      amount of normal spliced ATP7A transcripts were expressed. This is the first
      report of a synonymous ATP7A substitution being responsible for MD. 

PMID- 24100246
TI  - Evaluation of quality of life in PKU before and after introducing
      tetrahydrobiopterin (BH4); a prospective multi-center cohort study.
AB  - BACKGROUND: Phenylketonuria (PKU) is a rare inborn error of metabolism caused by
      phenylalanine hydroxylase enzyme (PAH) deficiency. Treatment constitutes a strict
      Phe restricted diet with unpalatable amino acid supplements. Residual PAH
      activity enhancement with its cofactor tetrahydrobiopterin (BH4) is a novel
      treatment which increases dietary tolerance in some patients and permits dietary
      relaxation. Relaxation of diet may improve health related quality of life
      (HRQoL). This prospective cohort study aims to evaluate HRQoL of patients with
      PKU and effects of BH4 treatment on HRQoL. METHODS: Patients aged 4years and
      older, diagnosed through newborn screening and early and continuously treated,
      were recruited from eight metabolic centers. Patients and mothers completed
      validated generic and chronic health-conditions HRQoL questionnaires (PedsQL,
      TAAQOL, and DISABKIDS) twice: before and after testing BH4 responsivity. Baseline
      results were compared to the general population. Data collected after BH4 testing
      was used to find differences in HRQoL between BH4 unresponsive patients and BH4
      responsive patients after one year of treatment with BH4. Also a within patient
      comparison was performed to find differences in HRQoL before and after treatment
      with BH4. RESULTS: 69/81 (85%) patients completed the questionnaires before BH4
      responsivity testing, and 45/69 (65%) participated again after testing. Overall
      PKU patients demonstrated normal HRQoL. However, some significant differences
      were found when compared to the general population. A significantly higher (thus
      better) score on the PedsQL was reported by children 8-12 years on physical
      functioning and by children 13-17 years on total and psychosocial functioning.
      Furthermore, adult patients reported significantly lower (thus worse) scores in
      the TAAQOL cognitive domain. 10 patients proved to be responsive to BH4
      treatment; however improvement in their HRQoL after relaxation of diet could not
      be demonstrated.

PMID- 24100247
TI  - Enzyme augmentation therapy enhances the therapeutic efficacy of bone marrow
      transplantation in mucopolysaccharidosis type II mice.
AB  - Before the availability of an enzyme replacement therapy (ERT) for
      mucopolysaccharidosis type II (MPS II), patients were treated by bone marrow
      transplantation (BMT). However, the effectiveness of BMT for MPS II was
      equivocal, particularly at addressing the CNS manifestations. To study this
      further, we subjected a murine model of MPS II to BMT and evaluated the effect at
      correcting the biochemical and pathological aberrations in the viscera and CNS.
      Our results indicated that BMT reduced the accumulation of glycosaminoglycans
      (GAGs) in a variety of visceral organs, but not in the CNS. With the availability
      of an approved ERT for MPS II, we investigated and compared the relative merits
      of the two strategies either as a mono or combination therapy. We showed that the
      combination of BMT and ERT was additive at reducing tissue levels of GAGs in the
      heart, kidney and lung. Moreover, ERT conferred greater efficacy if the
      immunological response against the infused recombinant enzyme was low. Finally,
      we showed that pathologic GAGs might potentially represent a sensitive biomarker
      to monitor the therapeutic efficacy of therapies for MPS II.

PMID- 24100248
TI  - Epileptic qualia and self-awareness: a third dimension for consciousness.
AB  - Over the last few decades, there has been increasing awareness among
      epileptologists about the need to refine our understanding and assessment of
      ictal consciousness, focusing on both subjective and behavioral aspects of
      seizures. Specifically, there have been suggestions that both the internal and
      external milieux - the former related to the phenomenal qualia of experience, the
      latter related to behavior - must be taken into account for a better
      understanding of altered states of consciousness in epilepsy. It has been
      proposed that clinical and experimental data from patients experiencing
      alterations of consciousness during epileptic seizures could be better understood
      within a bidimensional model, in which any manifestation of conscious experience
      can be plotted according to the level and contents of consciousness. The 'level'
      axis measures the degree of alertness/arousal, whereas the 'contents' axis
      measures the vividness of specific experiential phenomena reported by the
      patient. We argue that certain seizure types might require more rigorous
      conceptual models for their characterization, and we highlight the potential
      usefulness of a more refined framework which includes a further dimension related
      to the 'self', in addition to those of 'level' and 'contents'. This model could
      be visualized in a three-dimensional space to allow fine-grained distinctions
      between epileptic seizures.

PMID- 24100250
TI  - Validation of the Greek version of the Neurological Disorders Depression
      Inventory for Epilepsy (NDDI-E).
AB  - The Neurological Disorders Depression Inventory for Epilepsy (NDDI-E) was
      developed as a screening tool for symptoms of major depressive episodes in people
      with epilepsy. Our study describes the development, validation, and psychometric
      properties of the Greek version of the NDDI-E. A consecutive sample of 101
      patients with epilepsy, eligible to participate in the study, has been assessed
      using the Mini International Neuropsychiatric Interview version 5.0.0 and the
      NDDI-E. All patients had no major difficulties in understanding or answering the
      questions of the Greek version. Cronbach's alpha coefficient was 0.74. Receiver
      operating characteristic analysis showed an area under the curve of 91% (95%
      CI=83%-99%; SE: 0.040, p<0.001). At a cutoff score of greater than 15, the NDDI-E
      showed a sensitivity of 91%, a specificity of 81%, and a negative predictive
      value of 97%. 

PMID- 24100249
TI  - Gene therapy for epilepsy.
AB  - Gene therapy may represent an effective alternative to standard pharmacological
      approaches for certain forms of epilepsy. Currently, the best candidates for this
      therapeutic approach appear to be epilepsies characterized by a focal lesion.
      Gene therapy has been attempted to produce antiepileptogenic (prevention of
      development of epilepsy in subject at risk after having received an epileptogenic
      insult), antiseizure (reduction of frequency and/or severity of seizures), and
      disease-modifying (alteration of the natural history of the disease) effects. An
      example of gene therapy aimed at producing antiepileptogenic effects is a
      combination therapy based on the supplementation of the neurotrophic factors
      brain-derived neurotrophic factor (BDNF) and fibroblast growth factor 2 (FGF-2).
      Antiseizure effects have been obtained by increasing the strength of inhibitory
      signals (by supplementing specific GABAA receptor subunits or inhibitory
      neuropeptides like galanin or neuropeptide Y) or by reducing the strength of
      excitatory signals (by knocking down NMDA receptor subunits). This review
      summarizes the results obtained to date using gene therapy in epilepsy models and
      discusses the challenges and the opportunities that this approach can offer for
      the treatment of human epilepsies.

PMID- 24100251
TI  - A novel kindling model of temporal lobe epilepsy in rhesus monkeys induced by
      Coriaria lactone.
AB  - One of the major challenges in developing novel therapeutics for human epileptic
      disorders derives from the limitation of knowledge of the processes by which
      epilepsy is generated (epileptogenesis). Furthermore, the inability to obtain
      human samples at the early stage of epilepsy hinders studies designed to further
      understand epileptogenesis. Thus, an effective animal model is critical for
      studies investigating this process. The purpose of this study was to establish a
      new primate kindling model of temporal lobe epilepsy (TLE) as an animal model of
      epileptogenesis. Here, repeated injections of Coriaria lactone (CL) at a
      subthreshold dose elicited partial seizures that culminated in secondarily
      generalized tonic-clonic seizures. The sequence of events and features of the
      behaviors observed in this model simulated those observed in human TLE.
      Electroencephalogram monitoring revealed the temporal lobe origins of the
      epileptiform potentials, which were consistent with the behavioral changes
      observed. A total of 7 rhesus monkeys (78%) were kindled with a median of 48 (41
      to 60) CL injections. Both the seizure-induction and mortality rates were dose
      dependent. A CL injection at 1.50mg/kg showed the lowest animal mortality rate
      (0%) and the highest seizure-induction rate (100%). Extensive kindling by CL
      injections with a median of 97 injections (overkindling) subsequently resulted in
      the recurrence of spontaneous seizures in rhesus monkeys with frequency patterns
      that were similar to those observed in human TLE. In addition, rhesus monkeys
      subjected to large numbers of kindling stimuli displayed mitochondrial damage and
      astrocyte activation in a pattern that was similar to the neuropathological
      changes characteristic of human TLE. Thus, a kindling TLE model in rhesus monkeys
      representing a primate animal model of epileptogenesis was established for the
      first time using repeated intramuscular injections of Coriaria lactone. This
      model was easily and efficiently performed and resulted in behavioral,
      electrographical, and anatomical characteristics of human TLE. Thus, this model
      might be used in future investigations of the mechanisms involved in the
      epileptogenesis of TLE and in the development of new antiepileptic drugs. 

PMID- 24100252
TI  - Functional neuroanatomy of disorders of consciousness.
AB  - Our understanding of the mechanisms of loss and recovery of consciousness,
      following severe brain injury or during anesthesia, is changing rapidly. Recent
      neuroimaging studies have shown that patients with chronic disorders of
      consciousness and subjects undergoing general anesthesia present a complex
      dysfunctionality in the architecture of brain connectivity. At present, the
      global hallmark of impaired consciousness appears to be a multifaceted
      dysfunctional connectivity pattern with both within-network loss of connectivity
      in a widespread frontoparietal network and between-network hyperconnectivity
      involving other regions such as the insula and ventral tegmental area. Despite
      ongoing efforts, the mechanisms underlying the emergence of consciousness after
      severe brain injury are not thoroughly understood. Important questions remain
      unanswered: What triggers the connectivity impairment leading to disorders of
      consciousness? Why do some patients recover from coma, while others with
      apparently similar brain injuries do not? Understanding these mechanisms could
      lead to a better comprehension of brain function and, hopefully, lead to new
      therapeutic strategies in this challenging patient population.

PMID- 24100253
TI  - Beneficial effects of pioglitazone on atrial structural and electrical remodeling
      in vitro cellular models.
AB  - It has been demonstrated that atrial remodeling contributes toward atrial
      fibrillation (AF) maintenance and angiotensin II (AngII) is involved in the
      pathogenesis of atrial remodeling. Peroxisome proliferator-activated receptor
      gamma (PPAR-gamma) agonists have been shown to inhibit atrial remodeling.
      However, the underlying mechanisms are poorly understood. In the present study we
      investigated the regulating effects of PPAR-gamma agonist on AngII-induced atrial
      structural and electrical remodeling in vitro cellular models. The effects of
      pioglitazone on AngII-induced connective tissue growth factor (CTGF) expression
      and cell proliferation were assessed in primary-cultured mouse atrial
      fibroblasts. The influences of pioglitazone on AngII-induced L-type calcium
      channel (ICa-L) alpha1c expression and current density were evaluated in atrial
      myocytes (HL-1). Pioglitazone attenuated AngII-induced CTGF expression and
      proliferation in atrial fibroblasts, and pioglitazone also inhibited the
      expression or phosphorylation of AngII-induced transforming growth factor-beta1
      (TGF-beta1), tumor necrosis factor receptor associated factor 6 (TRAF6), TGF-beta
      associated kinase 1 (TAK1) and Smad2/3. In HL-1 cells, pioglitazone suppressed
      AngII-induced ICa-L alpha1c expression and current density as well as CAMP
      responsive element binding protein (CREB) phosphorylation. Besides, pioglitazone
      inhibited AngII-induced production of AngII type I receptor (AT1R) and
      downregulation of PPAR-gamma in both atrial fibroblasts and HL-1 cells. In
      conclusion, Pioglitazone suppresses AngII-induced CTGF expression and
      proliferation in atrial fibroblasts, which might be at least in part related with
      its inhibitory effects on TGF-beta1/Smad2/3 and TGF-beta1/TRAF6/TAK1 signaling
      pathways. Moreover, pioglitazone also attenuates AngII-induced ICa-L remodeling
      in HL-1 cells, which might be at least in part associated with its inhibitory
      effect on CREB phosphorylation. It is suggested that PPAR-gamma agonist may have
      potential applications in preventing atrial remodeling. 

PMID- 24100254
TI  - Toxicological Concerns of Engineered Nanosize Drug Delivery Systems.
AB  - Matters when converted into nanosize provide some unique surface properties,
      which are different from those of the bulk materials. Nanomaterials show some
      extraordinary behavioral patterns because of those properties, such as
      supermagnetism, quantum confinement, etc. A great deal of implication of
      nanomaterials in nanomedicine has already been realized. Utility of nanomaterials
      as drug nanocarrier projects many potential advantages of them in drug delivery.
      Despite many such advantages, the potential risk of health and environmental
      hazards related to them cannot be ignored. Here various physicochemical factors,
      such as chemical nature, degradability, surface properties, surface charge,
      particle size, and shape, have been shown to play a crucial role in toxicity
      related to drug nanocarriers. Evidence-based findings of some drug nanocarriers
      have been incorporated to provide distinct knowledge to the readers in the field.
      A glimpse of current regulatory controls and measures required to combat the
      challenges of toxicological aspects of drug nanocarriers have been described. 

PMID- 24100255
TI  - Development of acute pulmonary hypertension after bortezomib treatment in a
      patient with multiple myeloma: a case report and the review of the literature.
AB  - Bortezomib is widely used in treatment of multiple myeloma. In recent years,
      severe bortezomib-induced lung injury has been reported. The clinical course is
      generally characterized with fever and dyspnea, followed by respiratory failure
      with pulmonary infiltrates. Herein, we report a 57-year-old man with newly
      diagnosed multiple myeloma admitted with dyspnea, fever, and hypotension on the
      third day of the first dose of bortezomib therapy. He had bilateral jugular
      venous distention, crackles at the bases of the lungs and hepatomegaly.
      Transthoracic echocardiography revealed acute pulmonary hypertension (PH) with an
      estimated pressure of 70 mm Hg. The perfusion scintigraphy ruled out pulmonary
      embolism, and microbiological examination was negative. On his course, fever,
      dyspnea, hypoxia, and pulmonary vascular pressure subsided rapidly. The sudden
      onset of PH and its rapid decrement without any treatment suggests bortezomib as
      the underlying cause. Subsequently, the patient did not respond to vincristine
      doxorubicin-dexamethasone regimen and thalidomide. Bortezomib treatment was
      repeated, and no pulmonary adverse reactions occurred. Follow-up
      echocardiographies revealed pulmonary arterial pressures to be maximally of 35 mm
      Hg. To our knowledge, this is the first case of acute PH after front-line
      bortezomib therapy. In this report, we review bortezomib-related pulmonary
      complications in the literature and possible underlying mechanisms.

PMID- 24100256
TI  - A Randomized Comparison of Remifentanil Target-Controlled Infusion Versus
      Dexmedetomidine Single-Dose Administration: A Better Method for Smooth Recovery
      From General Sevoflurane Anesthesia.
AB  - Remifentanil target-controlled infusion and dexmedetomidine single-dose
      administration are known to reduce airway response and hemodynamic stimulation
      during anesthetic recovery. We compared the effects of 2 drugs on the prevention
      of cough during emergence. We enrolled 70 female patients aged 20-60 years with
      American Society of Anesthesiologists (ASA) I-II who underwent general anesthesia
      for elective thyroidectomy. The patients were randomly assigned to remifentanil
      (group R) or dexmedetomidine (group D). Anesthesia was maintained with
      sevoflurane and effect-site target-controlled infusion of remifentanil. In group
      D, remifentanil was discontinued, and dexmedetomidine 0.5 MUg/kg was given 10
      minutes before the end of surgery. In group R, remifentanil target-controlled
      infusion at an effective-site concentration of 2.0 ng/mL was maintained during
      emergence until extubation. The cough grade, hemodynamic values, respiration, and
      other recovery profiles were evaluated during the periextubation period. The
      proportion of patients with no cough or just a single cough during extubation was
      significantly higher in group R than in group D (96.8% vs. 55.9%). The change of
      mean arterial pressure and heart rate were not significantly different during
      extubation in both groups. Respiratory rate and the incidence of residual
      sedation after extubation were lower in group R. There were no desaturation
      events and no differences in time to extubation or duration of postanesthesia
      care unit stay in both groups. Remifentanil target-controlled infusion reduces
      emergence cough from general anesthesia more effectively than single-dose
      dexmedetomidine. However, a single-dose of dexmedetomidine has the effect with
      respect to respiratory and hemodynamic stability during emergence. 

PMID- 24100257
TI  - Takotsubo syndrome (or apical ballooning syndrome) secondary to Zolmitriptan.
AB  - Takotsubo syndrome (TS), also known as broken heart syndrome, is characterized by
      left ventricle apical ballooning with elevated cardiac biomarkers and
      electrocardiographic changes suggestive of an acute coronary syndrome (ie, ST
      segment elevation, T wave inversions, and pathologic Q waves). We report a case
      of 54-year-old woman with medical history of mitral valve prolapse and migraines,
      who was admitted to the hospital for substernal chest pain and electrocardiogram
      demonstrated 1/2 mm ST-segment elevation in leads II, III, aVF, V5, and V6 and
      positive troponin I. Emergent coronary angiogram revealed normal coronary
      arteries with moderately reduced left ventricular ejection fraction with wall
      motion abnormalities consistent with TS. Detailed history obtained
      retrospectively revealed that the patient took zolmitriptan sparingly only when
      she had migraines. But before this event, she was taking zolmitriptan 2-3 times
      daily for several days because of a persistent migraine headache. She otherwise
      reported that she is quite active, rides horses, and does show jumping without
      any limitations in her physical activity. There was no evidence of any recent
      stress or status migrainosus. Extensive literature search revealed multiple cases
      of coronary artery vasospasm secondary to zolmitriptan, but none of the cases
      were associated with TS. 

PMID- 24100258
TI  - Colchicine: New Insights to an Old Drug.
AB  - Colchicine is an ancient drug that is used for symptomatic relief in a wide range
      of inflammatory diseases including gout, Behcet syndrome, and familial
      Mediterranean fever. Recognition of its antiinflammatory properties and of its
      unpleasant gastrointestinal side effects date back thousands of years. Despite
      this, uncertainty remains concerning its mechanism of action and very few
      randomized controlled trials have been carried out to examine its safety and
      efficacy to date. Although it is an effective drug, its use is hindered by a very
      narrow therapeutic index. This review attempts to summarize recent developments
      concerning the use of colchicine in the treatment of gout with particular focus
      on its mechanism of action and toxicity. 

PMID- 24100259
TI  - Age and gender as predictors of benefit from aminophylline administration in
      patients undergoing regadenoson stress myocardial perfusion imaging: a substudy
      of the ASSUAGE trial.
AB  - Regadenoson is a selective adenosine A2A-receptor agonist, used as a
      pharmacological stress agent for myocardial perfusion imaging. It is associated
      with frequent adverse effects (AEs), particularly among individuals younger than
      65 years of age and women. Intravenous aminophylline administration following
      regadenoson, as described in the ASSUAGE trial, reduces the incidence of AE. In
      this substudy of the ASSUAGE trial, we compared the absolute and relative
      benefits of aminophylline administration versus placebo, between subgroups of age
      (<65 vs. >=65 years) and gender (women vs. men). Study endpoints were headache,
      gastrointestinal AE, any regadenoson AE, and tolerability (feeling comfortable
      during regadenoson stress). Among patients <65years, compared with >=65 years,
      aminophylline administration was associated with greater absolute risk reduction
      (ARR) in gastrointestinal AE (16% vs. 5%, P = 0.01) and any regadenoson AE (31%
      vs. 12%, P = 0.001), and with a greater absolute improvement in tolerability (21%
      vs. 1%, P < 0.001). Men received greater ARR in gastrointestinal AE than women
      (18% vs. 2%, P < 0.001). There was no difference in the ARR in other AE between
      subgroups. Across all subgroups, aminophylline use was associated with a
      consistent trend toward relative reduction in AE rates and improved tolerability.
      No significant interaction was identified between subgroups and aminophylline
      administration in reducing AE. In conclusion, although aminophylline use was
      associated with greater ARR in AE in certain subgroups, a consistent benefit with
      aminophylline administration was attained in all subgroups. Thus, to predictably
      reduce regadenoson AE and improve tolerability, aminophylline should be
      administered routinely to all patients as per the ASSUAGE protocol. 

PMID- 24100260
TI  - A comparative adsorption study of C2H4 and SO2 on clinoptilolite-rich tuff:
      effect of acid treatment.
AB  - In this study, ethylene (C2H4) and sulphur dioxide (SO2) adsorption properties of
      clinoptilolite tuff from Gordes, Turkey and that of acid treated forms were
      studied at 293K using volumetric apparatus up to 38 and 100 kPa, respectively. In
      order to consider the effect of acid treatment on structural and gas adsorption
      properties of zeolite, clinoptilolite mineral was modified with 0.1, 0.5, 1.0 and
      2.0M HCl solutions at 70  degrees C during 3h. XRD, XRF, TG/DTG, DTA and N2
      adsorption methods were employed for thermal and structural characterization of
      clinoptilolite samples before and after the acid treatment. SO2 adsorption
      capacities (2.356-2.739 mmol/g) of the clinoptilolite samples were superior to
      those of the C2H4 adsorptions (0.619-1.219 mmol/g).

PMID- 24100261
TI  - Cohort study of non-alcoholic fatty liver disease, NAFLD fibrosis score, and the
      risk of incident diabetes in a Korean population.
AB  - OBJECTIVES: No study has evaluated an association between non-alcoholic fatty
      liver disease (NAFLD) severity and the incidence of diabetes. We examined whether
      NAFLD and its severity-using the NAFLD fibrosis score (NFS)-predict the
      development of diabetes. METHODS: A cross-sectional study was performed in 43,166
      apparently healthy Koreans aged 30-59 years, who underwent a health checkup in
      2005 and 2006. Of these, 38,291 subjects without diabetes were followed annually
      or biennially until December 2011 for the cohort study. NAFLD was defined as
      hepatic steatosis on ultrasonography in the absence of excessive alcohol use or
      other identifiable causes. The NFS was used to categorize the severity of
      fibrosis. Diabetes was defined as fasting serum glucose >=126 mg/dl, glycated
      hemoglobin (HbA1c) >=6.5%, or medication use for diabetes. RESULTS: During
      175,996 person-years of follow-up, 2,025 participants developed diabetes. An
      increase across NAFLD categories was positively associated with an increased risk
      of diabetes in both the cross-sectional and cohort studies in a dose-response
      manner (P-trend <0.001). In multivariate-adjusted models, the hazard ratios (95%
      confidence intervals) for diabetes comparing NAFLD with low NFS and NAFLD with
      intermediate or high NFS vs. no NAFLD were 2.00 (1.79-2.24) and 4.74 (3.67-6.13),
      respectively. This association remained significant even in subjects with fasting
      glucose <100 mg/dl and subjects with HbA1c <5.8%. CONCLUSIONS: In this cohort
      study of a healthy Korean population, NAFLD and its severity using NFS were
      independently and strongly associated with increased incidence of diabetes in men
      and women-even with a euglycemic range of glucose and HbA1c.

PMID- 24100262
TI  - Rescuing infertility of Pick1 knockout mice by generating testis-specific
      transgenic mice via testicular infection.
AB  - PICK1 (protein interacting with C-kinase 1) is a peripheral membrane protein with
      high expression in brain, testis, pancreas and other neuroendocrine tissues. Male
      Pick1 knockout mice are completely infertile, with a phenotype resembling the
      human disease globozoospermia. Since PICK1 is expressed in both testis and
      neuroendocrine tissues, infertility of Pick1 knockout mice may be due to either
      impaired neuroendocrine function or abnormal spermatogenesis. To distinguish
      these two possibilities, we restored PICK1's expression in the testis by
      seminiferous tubule microinjection of PICK1-containing lentivirus. By examining
      the testis-specific Pick1 transgenic mice, we found that PICK1's expression in
      testis rescued the spermatogenic abnormalities and male infertility in Pick1
      knockout mice. Our results indicate that the infertility is caused by the lack of
      PICK1 in the testis rather than in other organs. In addition, we found that
      seminiferous tubule microinjection of lentivirus has a strong preference to
      produce testis-specific transgenic mice. 

PMID- 24100263
TI  - Localization of exogenous DNA to mitochondria in skeletal muscle following
      hydrodynamic limb vein injection.
AB  - Mitochondrial genetic disorders are a major cause of mitochondrial diseases. It
      is therefore likely that mitochondrial gene therapy will be useful for the
      treatment of such diseases. Here, we report on the possibility of mitochondrial
      gene delivery in skeletal muscle using hydrodynamic limb vein (HLV) injection.
      The HLV injection procedure, a useful method for transgene expression in skeletal
      muscle, involves the rapid injection of a large volume of naked plasmid DNA
      (pDNA) into the distal vein of a limb. We hypothesized that the technique could
      be used to deliver pDNA not only to nuclei but also to mitochondria, since
      cytosolic pDNA that is internalized by the method may be able to overcome
      mitochondrial membrane. We determined if pDNA could be delivered to myofibrillar
      mitochondria by HLV injection by PCR analysis. Mitochondrial toxicity assays
      showed that the HLV injection had no influence on mitochondrial function. These
      findings indicate that HLV injection promises to be a useful technique for in
      vivo mitochondrial gene delivery. 

PMID- 24100264
TI  - Profibrotic effect of miR-33a with Akt activation in hepatic stellate cells.
AB  - MicroRNAs (miRNAs) attract more attention in the pathophysiology of liver
      fibrosis and miR-33a has been previously demonstrated as involved in the
      regulation of cholesterol and lipid metabolism. Transforming growth factor-beta1
      (TGF-beta1) is generally accepted to be the main stimulating factor in the
      hepatic stellate cells (HSCs) activation, which plays an important role in
      hepatic fibrosis. However, the involvement and underlying mechanism of miR-33a
      and its role in TGF-beta1-induced hepatic fibrogenesis remains unknown. Here, we
      investigate the role of miR-33a in the activation of immortalized human HSCs, Lx
      2 cells. Our findings have shown that the expression of miR-33a with its host
      gene sterol regulatory element-binding protein 2 (SREBP2) was more highly
      expressed in activation of Lx-2 cells than in quiescent cells. The expression of
      miR-33a on TGF-beta1-induced HSCs activation may be modulated via the activation
      of PI3K/Akt pathway. In addition, miR-33a significantly correlated with TGF-beta1
      induced expression of alpha1 (I) collagen (Col1A1) and alpha-SMA in HSCs.
      Bioinformatics analyses predict that peroxisome proliferator activated receptor
      alpha (PPAR-alpha) is the potential target of miR-33a. We further found that anti
      miR-33a significantly increases target gene PPAR-alpha mRNA and protein level,
      suggesting that miR-33a involved in HSCs function might be modulated by targeting
      PPAR-alpha. Finally, our results indicate that the expression of miR-33a
      increased with the progression of liver fibrosis. These results suggested that
      anti-miR-33a inhibit activation and extracellular matrix production, at least in
      part, via the activation of PI3K/Akt pathway and PPAR-alpha and anti sense of miR
      33a may be a novel potential therapeutic approach for treating hepatic fibrosis
      in the future. 

PMID- 24100265
TI  - Diabetes: Unravelling the enigma of T2DM and cardiovascular disease.

PMID- 24100267
TI  - Bone: Osteocalcin influences fetal brain development and adult brain function.

PMID- 24100268
TI  - Reproductive endocrinology: Predictive biomarkers of pre-eclampsia in women with
      T1DM.

PMID- 24100266
TI  - Diabetic nephropathy: diagnosis and treatment.
AB  - Nephropathy remains a major cause of morbidity and a key determinant of mortality
      in patients with type 1 or type 2 diabetes mellitus. Research is ongoing to
      identify biomarkers that in addition to albuminuria and glomerular filtration
      rate assist in the prediction and monitoring of renal disease in diabetes
      mellitus. Current strategies to treat this condition focus on intensification of
      glycaemic control and excellent control of blood pressure using regimens based on
      blockade of the renin-angiotensin system. Other approaches to control blood
      pressure and afford renoprotection are under active clinical investigation,
      including renal denervation and endothelin receptor antagonism. With increasing
      understanding of the underlying pathophysiological processes implicated in
      diabetic nephropathy, new specific renoprotective treatment strategies are
      anticipated to become available over the next few years. 

PMID- 24100269
TI  - Role of the methylcitrate cycle in growth, antagonism and induction of systemic
      defence responses in the fungal biocontrol agent Trichoderma atroviride.
AB  - Methylisocitrate lyase (MCL), a signature enzyme of the methylcitrate cycle,
      which cleaves methylisocitrate to pyruvate and succinate, is required for
      propionate metabolism, for secondary metabolite production and for virulence in
      bacteria and fungi. Here we investigate the role of the methylcitrate cycle by
      generating an mcl deletion mutant in the fungal biocontrol agent Trichoderma
      atroviride. Gene expression analysis shows that a basal expression of mcl is
      observed in all growth conditions tested. Phenotypic analysis of an mcl deletion
      mutant suggests the requirement of MCL in propionate resistance, growth, conidial
      pigmentation and germination, and abiotic stress tolerance. A plate confrontation
      assay did not show a difference between the WT and the Deltamcl strain in
      antagonism towards Botrytis cinerea. However, the Deltamcl strain displays
      reduced antagonism towards B. cinerea based on a secretion assay. Furthermore, an
      in vitro root colonization assay shows that the Deltamcl strain had reduced
      ability to colonize Arabidopsis thaliana roots, which results in reduced
      induction of systemic resistance towards B. cinerea. These data show that MCL is
      important not only for growth and development in T. atroviride but also in
      antagonism, root colonization and induction of defence responses in plants. 

PMID- 24100270
TI  - Mechanism of cadmium induced apoptosis in human peripheral blood lymphocytes: the
      role of p53, Fas and Caspase-3.
AB  - Cadmium (Cd) is a major pollutant of environment. It can be fatal to human. In
      spite of bulk of research and literatures, the mechanism of a fatality against
      human is still not understood completely. Toxic and carcinogenic effects of Cd in
      rodents and humans are well known. However, effects of Cd on induction of
      apoptosis are still elusive. This study indicates immunosuppression and
      immunotoxicity due to Cd exposure. Present study was undertaken to determine the
      mechanism of cell death in vitro in human peripheral blood lymphocytes induced by
      Cd. Our findings suggest the toxicity due to Cd is attributed to programmed cell
      death-apoptosis. IC50 was calculated at 21.74 MUM. A significant increase of
      expression of the pro-apoptotic genep53, Fas and Caspase-3 in human lymphocytes
      was found. Cd induced p53-dependent apoptosis through cooperation between Bak
      upregulation without changing the Bcl-2 and Bax expression. Data of this study
      compel to speculate that apoptosis may also be attributed to CD95/Fas complex
      formation, and p53 direct apoptogenic potential at mitochondria. It was confirmed
      by the increased expression of Caspase-3. Although, this work does not address
      all the questions regarding the mechanism of Cd induced apoptosis, but these
      findings establish an important role of p53 and mitochondrial function during
      apoptosis in human lymphocyte. Moreover, based upon our findings, the role of Fas
      in Cd induced apoptosis is also undeniable. Hence further investigations are
      required to understand the different mechanism involved into apoptosis of
      lymphocytes due to Cd exposure.

PMID- 24100271
TI  - Levels and distribution of organochlorine pollutants in primary dental tissues
      and bone of lamb.
AB  - This study examined the bioconcentration of selected organochlorine pollutants,
      tetra- and hexa-chlorobiphenyls with planar (PCB-80, PCB-169) and non-planar (PCB
      54, PCB-155) structure, and persistent organochlorine pesticides with planar
      [hexachlorobenzene (HCB)] and non-planar [1,1-bis (4-chlorophenyl)-2,2
      dichloroethene (4,4'-DDE)] structure in primary dental tissues (pulp, dentine,
      and enamel) and mandibular bone of lactationally exposed lambs, and compared it
      with the organochlorines distribution pattern in permanent dental tissues and
      bone. Also, the role of pollutants physicochemical properties and tissue specific
      characteristics in the bioconcentration was assessed. Residual levels of
      individual pollutants were analyzed by high-resolution gas chromatography with
      electron-capture detection. Our results showed that transfer of organochlorines
      to primary hard dental tissues was higher than to permanent hard dental tissues.
      Metabolically more stable, planar, and toxic organochlorines (e.g. PCB-169 and
      HCB) predominated in primary hard dental tissues, where they may represent a
      potential risk for developmental dental defects. 

PMID- 24100273
TI  - Modeling the paraelectric aging effect in the acceptor doped perovskite
      ferroelectrics: role of oxygen vacancy.
AB  - The time dependence of physical properties in the paraelectric phase was probed
      recently in a Mn(3+) doped (Ba0.8Sr0.2)TiO3 ceramic, providing a simple situation
      (without spontaneous polarization or domain walls) to quantify the role of the
      oxygen vacancy during aging. In the present study, we propose a quantitative
      model for paraelectric aging to understand how the distribution of the oxygen
      vacancy evolves with time and consequently influences the dielectric response of
      the paraelectric phase. First, by comparing dielectric behavior of paraelectric
      aging in a Mn(3+) doped (Ba0.75Sr0.25)TiO3 ceramic and the dielectric tunable
      effect, an internal bias field E(in) related to the oxygen vacancy is shown to
      exist in the paraelectric phase. Second, by introducing such a time dependent
      E(in) in a Landau-type model, we reproduce the dielectric response of Mn(3+)
      doped (Ba0.8Sr0.2)TiO3 ceramic during paraelectric aging. It is suggested that
      the increase of dielectric permittivity can be ascribed to the decrease of E(in)
      with time. The investigation of paraelectric aging is helpful for understanding
      the role of the oxygen vacancy in influencing the physical properties of
      ferroelectric materials.

PMID- 24100272
TI  - Autocrine/paracrine erythropoietin regulates migration and invasion potential and
      the stemness of human breast cancer cells.
AB  - Recent studies suggest that erythropoietin (EPO) has pleiotropic effects in
      several cell types in addition to hematopoietic cells; however, the role of EPO
      mediated cell signaling in nonhematopoietic cells, including in cancer cells,
      remains controversial. Here, we report our findings of autocrine/paracrine
      production of EPO by breast cancer cells and its functional significance. We
      detected a significant level of autocrine/paracrine EPO in the conditioned medium
      from the culture of SKBR3 breast cancer cells, particularly when the cells were
      cultured in hypoxia. Through knockdown of EPO and EPO receptor expression and
      experimental elevation of EPO receptor expression in SKBR3 breast cancer cells,
      we demonstrated novel roles of autocrine/paracrine EPO-mediated cell signaling in
      regulating migration and invasion potential and stemness-like properties of
      breast cancer cells. 

PMID- 24100274
TI  - Induced pluripotent stem cells are sensitive to DNA damage.
AB  - Induced pluripotent stem cells (iPSCs) resemble embryonic stem cells (ESCs) in
      morphology, gene expression and in vitro differentiation, raising new hope for
      personalized clinical therapy. While many efforts have been made to improve
      reprogramming efficiency, significant problems such as genomic instability of
      iPSCs need to be addressed before clinical therapy. In this study, we try to
      figure out the real genomic state of iPSCs and their DNA damage response to
      ionizing radiation (IR). We found that iPSC line 3FB4-1 had lower DNA damage
      repair ability than mouse embryonic fibroblast (MEF) cells, from which 3FB4-1line
      was derived. After the introduction of DNA damage by IR, the number of gamma-H2AX
      foci in 3FB4-1 increased modestly compared to a large increase seen in MEF,
      albeit both significantly (P<0.01). In addition, whole-genome sequencing analysis
      showed that after IR, 3FB4-1 possessed more point mutations than MEF and the
      point mutations spread all over chromosomes. These observations provide evidence
      that iPSCs are more sensitive to ionizing radiation and their relatively low DNA
      damage repair capacity may account for their high radiosensitivity. The
      compromised DNA damage repair capacity of iPSCs should be considered when used in
      clinical therapy. 

PMID- 24100275
TI  - Pluripotency of induced pluripotent stem cells.
AB  - Induced pluripotent stem (iPS) cells can be generated by forced expression of
      four pluripotency factors in somatic cells. This has received much attention in
      recent years since it may offer us a promising donor cell source for cell
      transplantation therapy. There has been great progress in iPS cell research in
      the past few years. However, several issues need to be further addressed in the
      near future before the clinical application of iPS cells, like the immunogenicity
      of iPS cells, the variability of differentiation potential and most importantly
      tumor formation of the iPS derivative cells. Here, we review recent progress in
      research into the pluripotency of iPS cells. 

PMID- 24100276
TI  - Essential role of AKT in tumor cells addicted to FGFR.
AB  - Tumor cells with genetic amplifications or mutations in the fibroblast growth
      factor receptor (FGFR) family are often addicted to FGFR and heavily dependent on
      its signaling to survive. Although it is critical to understand which signaling
      pathway downstream of FGFR plays an essential role to guide the research and
      development of FGFR inhibitors, it has remained unclear partly because the tool
      compounds used in the literature also hit many other kinases, making the results
      difficult to interpret. With the development of a potent FGFR-specific inhibitor,
      BGJ398, we are now able to dissect various pathways with low drug concentrations
      to minimize multiple-target effects. Importantly, here, we show that inhibition
      of FGFR signaling by BGJ398 leads to only transient inhibition of ERK1/2
      phosphorylation, whereas the inhibitory effect on AKT phosphorylation is
      sustainable, indicating that AKT, not ERK as commonly believed, serves as an
      appropriate pharmacodynamic biomarker for BGJ398. Although AKT inhibition by a
      pan-PI3K inhibitor alone has almost no effect on cell growth, heterologous
      expression of myr-AKT, an active form of AKT, rescues BGJ398-mediated suppression
      of tumor cell proliferation. These results indicate that AKT is an essential
      component downstream of FGFR. Finally, combination of the FGFR inhibitor BGJ398
      with rapamycin significantly inhibits AKT phosphorylation and enhances their
      antiproliferative effects in FGFR-addicted cells, suggesting an effective
      combination strategy for clinical development of FGFR inhibitors. 

PMID- 24100277
TI  - Sodium meta-arsenite induces reactive oxygen species-dependent apoptosis,
      necrosis, and autophagy in both androgen-sensitive and androgen-insensitive
      prostate cancer cells.
AB  - Sodium meta-arsenite (NaAsO2), a novel compound synthesized by Komipham
      International Co. Ltd, is an orally bioavailable, water-soluble trivalent
      arsenical that has shown potent cytotoxic activity in human solid cancer cells in
      vitro and in vivo, and is currently undergoing phase I/II clinical trials for the
      treatment of prostate cancer. In this study, mechanisms of cell death induced by
      sodium meta-arsenite were investigated. Sodium meta-arsenite reduced cell
      viability and increased the sub-G1 population in cell cycle analysis in both
      androgen-sensitive LNCaP and androgen-insensitive CWR22RV1 cells. The apoptosis
      induced by sodium meta-arsenite was associated with cleavage of caspases 3, 8,
      and 9, and poly (ADP-ribose) polymerase (PARP) and increased annexin V-positive
      cells, and was inhibited by the pan-caspase inhibitor Z-VAD-fmk. Sodium meta
      arsenite also increased the level of the autophagy marker microtubule-associated
      protein 1 light chain 3 (LC3)-II and the number of autophagic vacuoles as shown
      by electron microscopy. Both the autophagy inhibitor 3-methyladenine and the
      necrosis inhibitor necrostatin-1 blocked cell death induced by sodium meta
      arsenite. Moreover, sodium meta-arsenite led to the accumulation of intracellular
      reactive oxygen species (ROS) and N-acetyl-L-cysteine (NAC), a ROS scavenger,
      decreased sodium meta-arsenite-induced levels of cleaved PARP and LC3-II.
      Propidium iodide (PI) staining also showed that NAC restored membrane integrity,
      damaged by sodium meta-arsenite. Therefore, these results suggest that sodium
      meta-arsenite induces apoptotic, necrotic, and autophagic cell death through
      intracellular ROS accumulation in both androgen-sensitive and androgen
      insensitive prostate cancer cells and may be used as a new anticancer drug for
      the treatment of prostate cancer. 

PMID- 24100278
TI  - Zoledronic acid in the treatment of metastatic breast cancer.
AB  - Bone is the most common location of metastatic disease. Approximately 80% of all
      bone metastases are observed in patients with breast or prostate tumours and are
      responsible for more than 300 000 deaths every year. Treatment of malignant bone
      disease with bisphosphonates has been shown to reduce bone events and delay their
      onset, and several reviews and meta-analyses have confirmed the benefit of these
      drugs in controlling bone metastases. Zoledronic acid is a bisphosphonate that
      has been shown to delay or prevent the development of skeletal-related events in
      patients with bone metastases. Furthermore, compared with other bisphosphonates,
      zoledronic acid has also shown better pain control and various studies also
      suggest an improvement in quality of life, although with no impact on overall
      survival. The duration and optimal regimen for long-term zoledronic acid therapy
      have not yet been defined, but some studies suggest that continuing zoledronic
      acid therapy for more than 2 years could also extend its beneficial effect. 

PMID- 24100279
TI  - An EGFR/CD13 bispecific fusion protein and its enediyne-energized analog show
      potent antitumor activity.
AB  - Targeting to two or more objectives simultaneously has been pursued as a strategy
      to potentially increase the efficiency and selectivity of targeted drugs to
      certain cancers. In this study, an epidermal growth factor receptor (EGFR)/CD13
      targeting, bispecific fusion protein ER(Fv)-LDP-NGR consisting of an anti-EGFR
      single-chain variable fragment (scFv), an apoprotein (LDP) of lidamycin (LDM),
      and a tri-CNGRC (Cys-Asn-Gly-Arg-Cys) peptide against CD13 was constructed, and
      then an enediyne-energized analog ER(Fv)-LDP-NGR-AE was generated by integration
      with an enediyne chomophore (AE) derived from LDM. The apoprotein LDP was used as
      a 'scaffold' to connect the scFv fragment and the tri-CNGRC peptide and also
      served as a specific 'carrier' for the extremely potent cytotoxic enediyne
      chromophore of LDM. Compared with its monospecific counterparts, ER(Fv)-LDP and
      LDP-NGR, the bispecific fusion protein ER(Fv)-LDP-NGR showed higher affinity to
      EGFR/CD13-overexpressed tumor cells. Determined by the MTT assay, the bispecific,
      enediyne-energized ER(Fv)-LDP-NGR-AE showed highly potent cytotoxicity to
      EGFR/CD13-overexpressed MCF-7 cells, with an IC50 value of 3.4*10 mol/l, whereas
      for the EGFR-overexpressed A431 cells, the IC50 value was 2.2*10 mol/l. For MCF-7
      cells, the bispecific ER(Fv)-LDP-NGR-AE was more potent in cytotoxicity than the
      corresponding monospecific energized fusion proteins. In athymic mice models, the
      bispecific fusion protein ER(Fv)-LDP-NGR presented stronger inhibitory activity
      than the monospecific ER(Fv)-LDP and LDP-NGR. For the enediyne-energized fusion
      proteins, ER(Fv)-LDP-NGR-AE significantly inhibited the growth of EGFR/CD13
      overexpressed MCF-7 xenograft and EGFR-overexpressed A431 xenograft by 86.3 and
      81.4%, respectively. In addition, the bispecific ER(Fv)-LDP-NGR-AE showed much
      higher efficacy than its monospecific analogs ER(Fv)-LDP-AE and LDP-NGR-AE in
      both MCF-7 and A431 xenograft models. The results show that EGFR/CD13 bitargeting
      effectively improved the antitumor efficacy. Both the bispecific fusion protein
      and its enediyne-energized analog are highly effective in athymic mice bearing
      xenografts, and the latter exerts more marked efficacy. Generation of a pair of
      bispecific antibody-based therapeutics and its corresponding antibody-drug
      conjugate simultaneously may be a feasible strategy for the development of new
      targeted drugs for cancer therapy. 

PMID- 24100280
TI  - Sinoporphyrin sodium: a novel sensitizer in sonodynamic therapy.
AB  - The aim of this paper was to investigate whether sinoporphyrin sodium (DVDMS)
      could be a novel sonosensitizer in sonodynamic therapy. We used two kinds of
      leukemia cells (K562, U937) as main tumor cell models and cells (peripheral blood
      mononuclear cells, spleen lymphocytes) separated from healthy ICR mice as normal
      cell models. The multivolume spectrophotometer system and fluorescence
      spectrophotometer were used to determine the spectral characteristics of DVDMS.
      The uptake of DVDMS by tumor cells and normal cells was measured by flow
      cytometry. The MTT assay was used to examine the cytotoxicity and sonotoxicity of
      DVDMS. The absorption spectra showed that DVDMS had five distinct peaks at 359,
      514, 548, 580, and 631 nm, respectively, and the maximum peak was at ~359 nm. The
      fluorescence emission spectra showed that DVDMS fluorescence emission was at 642
      nm. DVDMS showed an advantage of quick cellular uptake and selectively
      accumulated in tumor cells compared with normal healthy cells. The cytotoxicity
      of DVDMS by the MTT method was dose dependent, and DVDMS had little cytotoxicity
      to normal cells. The sonotoxicity of DVDMS showed that in the presence of DVDMS,
      under appropriate conditions, the cell-damaging effect of ultrasound was
      significantly enhanced. The present study showed that the newly synthesized
      sensitizer, DVDMS, under appropriate experiment conditions, can act as a
      potential sonosensitizer for tumors in sonodynamic therapy. 

PMID- 24100283
TI  - A national audit of the management of young people in genitourinary medicine
      clinics (level 3 services) in the United Kingdom.
AB  - Specialty and Associate Specialist (SAS) doctors in sexual health in the United
      Kingdom conducted this baseline audit against standards in the British
      Association of Sexual Health and HIV (BASHH) Management of STIs and related
      conditions in children and young people (2010) guideline: offer of screen
      (standard 90%), acceptance of screen (90%), completion of risk assessment
      proforma (100%), following a guideline (100%). Staff in 73 clinics submitted data
      for 2108 patient episodes. Of these clinics 68 (93%) follow BASHH guidelines and
      68 (93%) use a record proforma. Of the 2108 patients 1732 (82%) were assessed
      using a proforma. Where a proforma was used the records were more complete: data
      were present for 82% of four selected characteristics when a proforma was used
      and 33% of these characteristics when not used. Of the 2108 patients 1946 were at
      risk of infection, 1871 (96%) were offered tests and 1692 (90%) accepted.
      Standards were met on offer and acceptance of tests. Most participating clinics
      follow guidelines, but the standard of 100% was not met. Use of a proforma was
      frequent and was shown to improve assessment; the standard of 100% use was not
      met. The main recommendation is to implement conscientious use of a proforma at
      all clinics.

PMID- 24100284
TI  - Cost analysis and benefits of opt-out HIV testing at a tertiary care centre in
      northern India.
AB  - Currently, in India, the National AIDS Control Organization does not recommend
      HIV screening for all patients attending health care facilities. The objective of
      study was to evaluate cost and benefits of opt-out HIV testing at a tertiary care
      hospital from India. This is a retrospective cohort study of patients who had
      undergone HIV testing. The cost for HIV testing and cost per HIV-infected patient
      were determined. A total of 6512 patients (66.4% men and 905 patients younger
      than 14 years) with mean (SD) age of 30.3 (20.7) years were tested for HIV
      infection during the study period. Overall, 137 (2.1%) patients tested positive
      for HIV infection. Total cost for performing HIV tests during study period was
      Indian Rupees (INR) 649,319 (US dollar [USD] 11805.8). The estimated cost per
      person tested was INR 99.71 (USD1.8) and cost per HIV-infected patient identified
      and referred to the antiretroviral therapy centre was INR 4739.55 (USD86.2). We
      determined a 2.1% period prevalence estimate for HIV infection. Based on cost per
      HIV-infected patient identified and referred to the antiretroviral therapy centre
      and the burden of HIV infection, it may be cost effective to perform routine opt
      out screening for HIV infection in all patients attending health care facilities
      in developing countries like India.

PMID- 24100285
TI  - Genitourinary Medicine trainees' experience and training needs in the management
      of patients disclosing sexual violence.
AB  - The British Association for Sexual Health and HIV (BASHH) Sexual Violence group
      assessed the level of confidence of Genitourinary Medicine (GUM) trainees in
      managing patients disclosing sexual violence using an online survey. Twenty-eight
      percent of current UK GUM trainees responded. The results demonstrated wide
      variation in trainees' experience and confidence in managing these patients,
      which was dependent on the patient type, as well as the gender of the trainee and
      the number of years' experience the trainee had in the specialty. There were also
      differences in the reported availability of training in this specialist area.
      Regular accessible training in identification and management of patients
      disclosing sexual violence is recommended for GUM trainees.

PMID- 24100286
TI  - Self-reported time spent watching television is associated with arterial
      stiffness in young adults: the Amsterdam Growth and Health Longitudinal Study.
AB  - OBJECTIVES: To investigate whether time spent watching television (a marker of
      sedentary behaviour) is associated with arterial stiffness, a major determinant
      of cardiovascular disease, and whether any such association could be explained by
      related deleterious levels of habitual physical activity (HPA) and/or other
      lifestyle and biological risk factors. METHODS: Prospective measures (ages 32 and
      36 years) of television time and risk factors were retrieved from 373
      participants (196 women) in whom stiffness of the carotid, brachial and femoral
      arteries was assessed by means of ultrasonography at age 36 years. Data were
      analysed with generalised estimating equations. RESULTS: Participants with
      stiffer carotid arteries spent more time (in min/day) watching television during
      the four preceding years than did those with less stiff arteries, as defined on
      the basis of the highest compared with the lowest gender-specific tertiles of the
      distensibility or compliance coefficients (reversed) or the Young's elastic
      modulus: +22.4 (95%CI 8.7 to 36.1), +18.4 (4.2 to 32.5) and +19.7 (6.0 to 33.4),
      respectively. These differences were independent of potential confounders, such
      as vigorous intensity HPA and other lifestyle risk factors, and could only in
      part (up to 31%) be explained by the adverse associations of television time with
      traditional biological risk factors. Qualitatively similar results were found for
      femoral, but not brachial, stiffness estimates. CONCLUSIONS: Given the
      independent associations of time spent watching television and vigorous intensity
      HPA with arterial stiffness, our study suggests that not only promotion of
      physical activity, but also discouragement of sedentary behaviours should be
      targeted in younger adults to prevent arterial stiffening.

PMID- 24100287
TI  - The effectiveness of exercise interventions to prevent sports injuries: a
      systematic review and meta-analysis of randomised controlled trials.
AB  - BACKGROUND: Physical activity is important in both prevention and treatment of
      many common diseases, but sports injuries can pose serious problems. OBJECTIVE:
      To determine whether physical activity exercises can reduce sports injuries and
      perform stratified analyses of strength training, stretching, proprioception and
      combinations of these, and provide separate acute and overuse injury estimates.
      MATERIAL AND METHODS: PubMed, EMBASE, Web of Science and SPORTDiscus were
      searched and yielded 3462 results. Two independent authors selected relevant
      randomised, controlled trials and quality assessments were conducted by all
      authors of this paper using the Cochrane collaboration domain-based quality
      assessment tool. Twelve studies that neglected to account for clustering effects
      were adjusted. Quantitative analyses were performed in STATA V.12 and sensitivity
      analysed by intention-to-treat. Heterogeneity (I(2)) and publication bias
      (Harbord's small-study effects) were formally tested. RESULTS: 25 trials,
      including 26 610 participants with 3464 injuries, were analysed. The overall
      effect estimate on injury prevention was heterogeneous. Stratified exposure
      analyses proved no beneficial effect for stretching (RR 0.963 (0.846-1.095)),
      whereas studies with multiple exposures (RR 0.655 (0.520-0.826)), proprioception
      training (RR 0.550 (0.347-0.869)), and strength training (RR 0.315 (0.207-0.480))
      showed a tendency towards increasing effect. Both acute injuries (RR 0.647 (0.502
      0.836)) and overuse injuries (RR 0.527 (0.373-0.746)) could be reduced by
      physical activity programmes. Intention-to-treat sensitivity analyses
      consistently revealed even more robust effect estimates. CONCLUSIONS: Despite a
      few outlying studies, consistently favourable estimates were obtained for all
      injury prevention measures except for stretching. Strength training reduced
      sports injuries to less than 1/3 and overuse injuries could be almost halved.

PMID- 24100288
TI  - The role of proximal dynamic joint stability in the development of exertional
      medial tibial pain: a prospective study.
AB  - OBJECTIVE: To prospectively determine risk factors contributing to the
      development of exertional medial tibial pain (EMTP). METHODS: Data were
      prospectively collected on healthy female students in physical education, who
      were freshmen in 2010-2011 and 2011-2012. Eighty-six female students aged 19.38+/
      0.85 years, were tested at the beginning of their first academic year. Kinematic
      parameters in the frontal and transverse plane were measured during a single-leg
      drop jump (SLDJ). For further analysis, the SLDJ task was divided in two phases:
      touchdown until maximal knee flexion (MKF) and then MKF until take-off,
      representing landing and push-off phase, respectively. The injury follow-up of
      the students was assessed using a weekly online questionnaire and a 3-monthly
      retrospective control questionnaire. EMTP was diagnosed by an experienced medical
      doctor. Cox regression analysis was used to identify the potential risk factors
      for the development of EMTP. RESULTS: During injury follow-up (1-2 years), 22
      participants were diagnosed with EMTP. The results of this study identified that
      increased range of motion (ROM) in the transverse plane of hip and thorax during
      landing (p=0.010 and 0.026, respectively) and during push off (p=0.019 and 0.045,
      respectively) are predictive parameters for the development of EMTP in women.
      CONCLUSIONS: Increased ROM values of hip and thorax in the transverse plane,
      which can be interpreted as impaired ability to maintain dynamic joint stability
      resulting in increased accessory movements, are significant contributors to the
      development of EMTP in women.

PMID- 24100289
TI  - Inhaled salbutamol does not affect athletic performance in asthmatic and non
      asthmatic cyclists.
AB  - RATIONALE: Salbutamol may affect lung function and exercise performance
      differently in individuals with and without asthma. OBJECTIVES: To compare the
      effects of inhaled salbutamol on lung function, exercise performance and
      respiratory parameters during cycling exercise in athletes with a positive
      response to a eucapnic voluntary hyperpnoea (EVH+) and negative (EVH-) challenge,
      indicative of exercise-induced bronchoconstriction. METHODS: In a randomised
      controlled trial with a crossover design, a total of 49 well-trained male
      athletes (14 EVH+ and 35 EVH-) performed two simulated 10 km time-trials on a
      cycle ergometer 60 min after the inhalation of either 400 MUg of salbutamol or a
      placebo. Lung function, assessed by forced expiratory volume in 1 s, was measured
      immediately before and 30 min after inhalation. Performance was measured by mean
      power output. MEASUREMENTS & MAIN RESULTS: Despite a significant increase in lung
      function after the inhalation of salbutamol compared to the placebo (p<0.001),
      salbutamol did not affect athletes' perceptions of dyspnoea (p>0.05) or leg
      exertion (p>0.05) during exercise. Salbutamol did not affect mean power output:
      EVH+ and EVH- athletes averaged 4.0 (0.5) and 4.1 (0.5) W/kg after salbutamol and
      4.0 (0.5) W/kg and 4.0 (0.4) W/kg after placebo, respectively (p>0.05 for each
      comparison). CONCLUSIONS: The inhalation of salbutamol induced a significant
      increase in resting lung function in EVH+ and EVH- athletes but this improvement
      in lung function did not translate to improved exercise performance. Salbutamol
      had no discernible effect on key ventilatory and exercise parameters regardless
      of EVH challenge outcome.

PMID- 24100290
TI  - Greater glycosaminoglycan content in human patellar tendon biopsies is associated
      with more pain and a lower VISA score.
AB  - BACKGROUND: People with patellar tendinopathy experience chronic pain and
      activity limitation, but a pertinent biochemical marker correlated with these
      clinical features has not been identified. The Victoria Institute of Sport
      Assessment (VISA) questionnaire is a condition-specific patient-rated outcome
      measure. Since the quantity of glycosaminoglycans (GAGs) increases with advancing
      tendon pathology, we hypothesised that there would be a correlation between the
      quantity of GAGs in the patellar tendon and the VISA score. METHODS: Tissue
      biopsies from athletes with chronic patellar tendinopathy (confirmed by clinical
      examination and MRI) were recruited (n=7), as well as controls with no history of
      knee pain (n=4). The quantity of sulphated GAGs in the human patellar tendons was
      determined with a dimethyl methylene blue (DMMB) assay; this method was first
      validated with rat tendon tissue. The extent and distribution of GAG species and
      proteoglycans (decorin, versican and aggrecan) in the human tendon biopsies were
      examined using immunohistochemistry. RESULTS: Greater sulphated GAG content of
      the patellar tendon was correlated with the greater tendon dysfunction
      (R(2)=0.798). The quantity of aggrecan in the tendon, a chondroitin sulphate-rich
      proteoglycan, also increased with advancing tendon pathology. CONCLUSIONS:
      Increased GAGs in the pathological human patellar tendon are related to a worse
      clinical status. These findings indicate that the VISA score reflects the extent
      of tendon tissue pathology.

PMID- 24100291
TI  - Notch3 marks clonogenic mammary luminal progenitor cells in vivo.
AB  - The identity of mammary stem and progenitor cells remains poorly understood,
      mainly as a result of the lack of robust markers. The Notch signaling pathway has
      been implicated in mammary gland development as well as in tumorigenesis in this
      tissue. Elevated expression of the Notch3 receptor has been correlated to the
      highly aggressive "triple negative" human breast cancer. However, the specific
      cells expressing this Notch paralogue in the mammary gland remain unknown. Using
      a conditionally inducible Notch3-CreERT2(SAT) transgenic mouse, we genetically
      marked Notch3-expressing cells throughout mammary gland development and followed
      their lineage in vivo. We demonstrate that Notch3 is expressed in a highly
      clonogenic and transiently quiescent luminal progenitor population that gives
      rise to a ductal lineage. These cells are capable of surviving multiple
      successive pregnancies, suggesting a capacity to self-renew. Our results also
      uncover a role for the Notch3 receptor in restricting the proliferation and
      consequent clonal expansion of these cells. 

PMID- 24100292
TI  - Recruitment of the autophagic machinery to endosomes during infection is mediated
      by ubiquitin.
AB  - Although ubiquitin is thought to be important for the autophagic sequestration of
      invading bacteria (also called xenophagy), its precise role remains largely
      enigmatic. Here we determined how ubiquitin is involved in this process. After
      invasion, ubiquitin is conjugated to host cellular proteins in endosomes that
      contain Salmonella or transfection reagent-coated latex (polystyrene) beads,
      which mimic invading bacteria. Ubiquitin is recognized by the autophagic
      machinery independently of the LC3-ubiquitin interaction through adaptor
      proteins, including a direct interaction between ubiquitin and Atg16L1. To ensure
      that invading pathogens are captured and degraded, Atg16L1 targeting is secured
      by two backup systems that anchor Atg16L1 to ubiquitin-decorated endosomes. Thus,
      we reveal that ubiquitin is a pivotal molecule that connects bacteria-containing
      endosomes with the autophagic machinery upstream of LC3. 

PMID- 24100293
TI  - Patronin mediates a switch from kinesin-13-dependent poleward flux to anaphase B
      spindle elongation.
AB  - Anaphase B spindle elongation contributes to chromosome segregation during
      Drosophila melanogaster embryo mitosis. We propose that this process is driven by
      a kinesin-5-generated interpolar microtubule (MT; ipMT) sliding filament
      mechanism that engages when poleward flux is turned off. In this paper, we
      present evidence that anaphase B is induced by the minus end-stabilizing protein
      patronin, which antagonizes the kinesin-13 depolymerase KLP10A at spindle poles,
      thereby switching off the depolymerization of the minus ends of outwardly sliding
      ipMTs to suppress flux. Although intact cortices, kinetochore MTs, and midzone
      augmentation are dispensable, this patronin-based change in ipMT minus-end
      dynamics is sufficient to induce the elongation of spindles capable of separating
      chromosomes.

PMID- 24100294
TI  - An in vitro assay for entry into cilia reveals unique properties of the soluble
      diffusion barrier.
AB  - Specific proteins are concentrated within primary cilia, whereas others remain
      excluded. To understand the mechanistic basis of entry into cilia, we developed
      an in vitro assay using cells in which the plasma membrane was permeabilized, but
      the ciliary membrane was left intact. Using a diffusion-to-capture system and
      quantitative analysis, we find that proteins >9 nm in diameter (~100 kD) are
      restricted from entering cilia, and we confirm these findings in vivo.
      Interference with the nuclear pore complex (NPC) or the actin cytoskeleton in
      permeabilized cells demonstrated that the ciliary diffusion barrier is
      mechanistically distinct from those of the NPC or the axon initial segment.
      Moreover, applying a mass transport model to this system revealed diffusion
      coefficients for soluble and membrane proteins within cilia that are compatible
      with rapid exploration of the ciliary space in the absence of active transport.
      Our results indicate that large proteins require active transport for entry into
      cilia but not necessarily for movement inside cilia. 

PMID- 24100295
TI  - Sequestration of CDH1 by MAD2L2 prevents premature APC/C activation prior to
      anaphase onset.
AB  - The switch from activation of the anaphase-promoting complex/cyclosome (APC/C) by
      CDC20 to CDH1 during anaphase is crucial for accurate mitosis. APC/C(CDC20)
      ubiquitinates a limited set of substrates for subsequent degradation, including
      Cyclin B1 and Securin, whereas APC/C(CDH1) has a broader specificity. This switch
      depends on dephosphorylation of CDH1 and the APC/C, and on the degradation of
      CDC20. Here we show, in human cells, that the APC/C inhibitor MAD2L2 also
      contributes to ensuring the sequential activation of the APC/C by CDC20 and CDH1.
      In prometaphase, MAD2L2 sequestered free CDH1 away from the APC/C. At the onset
      of anaphase, MAD2L2 was rapidly degraded by APC/C(CDC20), releasing CDH1 to
      activate the dephosphorylated APC/C. Loss of MAD2L2 led to premature association
      of CDH1 with the APC/C, early destruction of APC/C(CDH1) substrates, and
      accelerated mitosis with frequent mitotic aberrations. Thus, MAD2L2 helps to
      ensure a robustly bistable switch between APC/C(CDC20) and APC/C(CDH1) during the
      metaphase-to-anaphase transition, thereby contributing to mitotic fidelity. 

PMID- 24100297
TI  - Structural, spectroscopic and electrical studies of nanostructured porous ZnO
      thin films prepared by pulsed laser deposition.
AB  - ZnO thin films are grown on quartz substrates at various substrate temperatures
      (ranging from 573 to 973 K) under an oxygen ambience of 0.02 mbar by using pulsed
      laser ablation. Influence of substrate temperature on the structural,
      morphological, optical and electrical properties of the ZnO thin films are
      investigated. The XRD and micro-Raman spectra reveal the presence of hexagonal
      wurtzite structure of ZnO with preferred orientation (002). The particle size is
      calculated using Debye-Scherer equation and the average size of the crystallites
      are found to be in the range 17-29 nm. The AFM study reveals that the surface
      morphology of the film depends strongly on the substrate temperature. UV-Visible
      transmittance spectra show highly transparent nature of the films in visible
      region. The calculated optical band gap energy is found to be decrease with
      increase in substrate temperatures. The complex dielectric constant, the loss
      factor and the distribution of the volume and surface energy loss of the ZnO thin
      films prepared at different substrate temperatures are calculated. All the films
      are found to be highly porous in nature. The PL spectra show very strong emission
      in the blue region for all the films. The dc electrical resistivity of the film
      decreases with increase in substrate temperature. The temperature dependent
      electrical measurements done on the film prepared at substrate temperature 573 K
      reveals that the electric conduction is thermally activated and the activation
      energy is found to be 0.03911 eV which is less than the reported values for ZnO
      films.

PMID- 24100296
TI  - Pin1 promotes histone H1 dephosphorylation and stabilizes its binding to
      chromatin.
AB  - Histone H1 plays a crucial role in stabilizing higher order chromatin structure.
      Transcriptional activation, DNA replication, and chromosome condensation all
      require changes in chromatin structure and are correlated with the
      phosphorylation of histone H1. In this study, we describe a novel interaction
      between Pin1, a phosphorylation-specific prolyl isomerase, and phosphorylated
      histone H1. A sub-stoichiometric amount of Pin1 stimulated the dephosphorylation
      of H1 in vitro and modulated the structure of the C-terminal domain of H1 in a
      phosphorylation-dependent manner. Depletion of Pin1 destabilized H1 binding to
      chromatin only when Pin1 binding sites on H1 were present. Pin1 recruitment and
      localized histone H1 phosphorylation were associated with transcriptional
      activation independent of RNA polymerase II. We thus identify a novel form of
      histone H1 regulation through phosphorylation-dependent proline isomerization,
      which has consequences on overall H1 phosphorylation levels and the stability of
      H1 binding to chromatin. 

PMID- 24100298
TI  - Instrumentation for diagnostics and control of laser-accelerated proton (ion)
      beams.
AB  - Suitable instrumentation for laser-accelerated proton (ion) beams is critical for
      development of integrated, laser-driven ion accelerator systems. Instrumentation
      aimed at beam diagnostics and control must be applied to the driving laser pulse,
      the laser-plasma that forms at the target and the emergent proton (ion) bunch in
      a correlated way to develop these novel accelerators. This report is a brief
      overview of established diagnostic techniques and new developments based on
      material presented at the first workshop on 'Instrumentation for Diagnostics and
      Control of Laser-accelerated Proton (Ion) Beams' in Abingdon, UK. It includes
      radiochromic film (RCF), image plates (IP), micro-channel plates (MCP), Thomson
      spectrometers, prompt inline scintillators, time and space-resolved
      interferometry (TASRI) and nuclear activation schemes. Repetition-rated
      instrumentation requirements for target metrology are also addressed. 

PMID- 24100299
TI  - The confluence of structure and dynamics in lanthanide(III) chelates: how
      dynamics help define structure in solution.
AB  - Coordination exchange processes tend to dominate the solution state behaviour of
      lanthanide chelates and generally prohibit the study of small conformational
      changes. In this article we take advantage of coordinatively rigid Eu(3+)
      chelates to examine the small conformational changes that occur in these chelates
      as water dissociatively exchanges in and out of the inner coordination sphere.
      The results show that the time-averaged conformation of the chelate alters as the
      water exchange rate increases. This conformational change reflects a change in
      the hydration state (q/r(LnH)(6)) of the chelate. The hydration state has
      recently come to be expressed as two separate parameters q and r(LnH). However,
      these two parameters simultaneously describe the same structural considerations
      which in solution are indistinguishable and intrinsically related to, and
      dependent upon, the dissociative water exchange rate. This realization leads to
      the broader understanding that a solution state structure can only be appreciated
      with reference to the dynamics of the system.

PMID- 24100300
TI  - Why does living donor liver transplantation flourish in Asia?
AB  - The success of liver transplantation worldwide has brought increased demand for
      the liver graft. Western and Asian countries have coped differently with the
      problems of the shortages in organ donation. In the West, efforts have focused on
      promoting deceased donor organ donation, whereas in Asia the focus has been on
      living donor liver transplantation (LDLT), as this procedure is more acceptable
      in most Asian cultures. LDLT, which was initially devised for paediatric liver
      transplant patients, has evolved from using a left lobe graft to a right lobe
      graft for an adult recipient. To widen the donor pool, dual grafts for a single
      recipient have been used in LDLT, and donors with hepatitis B core antibody
      positivity have been accepted, as well as ABO incompatible donors and recipients.
      The great advances in the field of LDLT have been dictated by the needs and the
      norms of Asian society. In this Perspectives article, we outline the reasons why
      LDLT flourishes in Asia.

PMID- 24100301
TI  - Paediatric gastroenterology: new algorithm successfully identifies infants at
      risk of progressive necrotising enterocolitis.

PMID- 24100302
TI  - Reply to: From the CUPIC study: great times are not coming (?).

PMID- 24100303
TI  - The transcription factor HNF1alpha induces expression of angiotensin-converting
      enzyme 2 (ACE2) in pancreatic islets from evolutionarily conserved promoter
      motifs.
AB  - Pancreatic angiotensin-converting enzyme 2 (ACE2) has previously been shown to be
      critical for maintaining glycemia and beta-cell function. Efforts to maintain or
      increase ACE2 expression in pancreatic beta-cells might therefore have
      therapeutic potential for treating diabetes. In our study, we investigated the
      transcriptional role of hepatocyte nuclear factor 1alpha (HNF1alpha) and
      hepatocyte nuclear factor 1beta (HNF1beta) in induction of ACE2 expression in
      insulin-secreting cells. A deficient allele of HNF1alpha or HNF1beta causes
      maturity-onset diabetes of the young (MODY) types 3 and 5, respectively, in
      humans. We found that ACE2 is primarily transcribed from the proximal part of the
      ACE2 promoter in the pancreas. In the proximal part of the human ACE2 promoter,
      we further identified three functional HNF1 binding sites, as they have binding
      affinity for HNF1alpha and HNF1beta and are required for induction of promoter
      activity by HNF1beta in insulinoma cells. These three sites are well-conserved
      among mammalian species. Both HNF1alpha and HNF1beta induce expression of ACE2
      mRNA and lead to elevated levels of ACE2 protein and ACE2 enzymatic activity in
      insulinoma cells. Furthermore, HNF1alpha dose-dependently increases ACE2
      expression in primary pancreatic islet cells. We conclude that HNF1alpha can
      induce the expression of ACE2 in pancreatic islet cells via evolutionarily
      conserved HNF1 binding sites in the ACE2 promoter. Potential therapeutics aimed
      at counteracting functional HNF1alpha depletion in diabetes and MODY3 will thus
      have ACE2 induction in pancreatic islets as a likely beneficial effect. 

PMID- 24100304
TI  - Redox responsive nanotubes from organometallic polymers by template assisted
      layer by layer fabrication.
AB  - Redox responsive nanotubes were fabricated by the template assisted layer-by
      layer (LbL) assembly method and employed as platforms for molecular payload
      release. Positively and negatively charged organometallic poly(ferrocenylsilane)s
      (PFS) were used to construct the nanotubes, in combination with other polyions.
      During fabrication, multilayers of these polyions were deposited onto the inner
      pores of template porous membranes, followed by subsequent removal of the
      template. Anodized porous alumina and track-etched polycarbonate membranes were
      used as templates. The morphology, electrochemistry, composition and other
      properties of the obtained tubular structure were characterized by fluorescence
      microscopy, scanning (SEM) and transmission electron microscopy (TEM) and energy
      dispersive X-ray (EDX) spectroscopy. Composite nanotubes, consisting of
      poly(acrylic acid) anions with PFS(+) and nanoparticles including fluorophore
      labelled dextran and decorated quantum dots, with PFS polyelectrolytes were also
      fabricated, broadening the scope of the structures. Cyclic voltammograms of PFS
      containing nanotubes showed similar redox responsive behaviour to thin LbL
      assembled films. Redox triggered release of labelled macromolecules from these
      tubular structures demonstrated application potential in controlled molecular
      delivery. 

PMID- 24100305
TI  - Effects of radioactive caesium on bull testes after the Fukushima nuclear plant
      accident.
AB  - We aimed to investigate the effect of chronic radiation exposure associated with
      the Fukushima Daiichi Nuclear Plant accident on the testis from 2 bulls.
      Estimated dose of internal exposure in one bull was 0.7-1.2 mGy (134Cs) and 0.4
      0.6 mGy (137Cs) and external exposure was 2.0 mGy (134Cs) and 0.8 mGy (137Cs)
      (196 days). Internal dose in the other was 3.2-6.1 mGy (134Cs) and 1.8-3.4 mGy
      (137Cs) and external dose was 1.3 mGy (134Cs) and 0.6 mGy (137Cs) (315 days).
      Sperm morphology and spermatogenesis were within normal ranges. 134,137Cs
      radioactivity was detected but Cs was not detectable in the testis by electron
      probe microanalysis. Thus, adverse radiation-induced effects were not observed in
      bull testes following chronic exposure to the above levels of radiation for up to
      10 months. Since we could analyse a limited number of testes, further
      investigation on the effects of ionizing radiation on spermatogenesis should be
      extended to more animals.

PMID- 24100306
TI  - On the propagation of errors.
AB  - The policy of the Protein Data Bank (PDB) that the first deposition of a small
      molecule ligand, even with erroneous atom numbering, sets a precedent over
      accepted nomenclature rules is disputed. Recommendations regarding ligand
      molecules in the PDB are suggested. 

PMID- 24100307
TI  - Structure of the periplasmic copper-binding protein CueP from Salmonella enterica
      serovar Typhimurium.
AB  - CueP was initially identified as a copper-resistance gene in Salmonella enterica
      serovar Typhimurium, which has evolved to survive in the phagosomes of
      macrophages. Recently, CueP was determined to be a periplasmic copper-binding
      protein and has been implicated in the transfer of copper ions to SodCII in the
      periplasm. In this study, the crystal structure of CueP has been determined,
      revealing a V-shaped dimeric structure. The conserved cysteine and histidine
      residues are clustered on the surface of one side of the C-terminal domain,
      suggesting that this cysteine- and histidine-rich region is related to the
      function of CueP. LC-MS/MS analysis established the presence of a disulfide bond
      between Cys96 and Cys176 under aerobic conditions. Subsequent biophysical
      analyses showed that the CueP protein binds copper and zinc, and the mutation of
      Cys104 to serine (C104S) dramatically reduced the binding affinity for copper and
      zinc, suggesting that the cysteine- and histidine-rich cluster is responsible for
      copper binding. This study provides a structural basis for the participation of
      CueP in the resistance of the intracellular pathogen Salmonella to copper. 

PMID- 24100308
TI  - Functional convergence of structurally distinct thioesterases from cyanobacteria
      and plants involved in phylloquinone biosynthesis.
AB  - The synthesis of phylloquinone (vitamin K1) in photosynthetic organisms requires
      a thioesterase that hydrolyzes 1,4-dihydroxy-2-naphthoyl-CoA (DHNA-CoA) to
      release 1,4-dihydroxy-2-naphthoate (DHNA). Cyanobacteria and plants contain
      distantly related hotdog-fold thioesterases that catalyze this reaction, although
      the structural basis of these convergent enzymatic activities is unknown. To
      investigate this, the crystal structures of hotdog-fold DHNA-CoA thioesterases
      from the cyanobacterium Synechocystis (Slr0204) and the flowering plant
      Arabidopsis thaliana (AtDHNAT1) were determined. These enzymes form distinct
      homotetramers and use different active sites to catalyze hydrolysis of DHNA-CoA,
      similar to the 4-hydroxybenzoyl-CoA (4-HBA-CoA) thioesterases from Pseudomonas
      and Arthrobacter. Like the 4-HBA-CoA thioesterases, the DHNA-CoA thioesterases
      contain either an active-site aspartate (Slr0204) or glutamate (AtDHNAT1) that
      are predicted to be catalytically important. Computational modeling of the
      substrate-bound forms of both enzymes indicates the residues that are likely to
      be involved in substrate binding and catalysis. Both enzymes are selective for
      DHNA-CoA as a substrate, but this selectivity is achieved using divergent
      predicted binding strategies. The Slr0204 binding pocket is predominantly
      hydrophobic and closely conforms to DHNA, while that of AtDHNAT1 is more polar
      and solvent-exposed. Considered in light of the related 4-HBA-CoA thioesterases,
      these structures indicate that hotdog-fold thioesterases using either an active
      site aspartate or glutamate diverged into distinct clades prior to the evolution
      of strong substrate specificity in these enzymes. 

PMID- 24100309
TI  - Complex structure of type VI peptidoglycan muramidase effector and a cognate
      immunity protein.
AB  - The type VI secretion system (T6SS) is a bacterial protein-export machine that is
      capable of delivering virulence effectors between Gram-negative bacteria. The
      T6SS of Pseudomonas aeruginosa transports two lytic enzymes, Tse1 and Tse3, to
      degrade cell-wall peptidoglycan in the periplasm of rival bacteria that are
      competing for niches via amidase and muramidase activities, respectively. Two
      cognate immunity proteins, Tsi1 and Tsi3, are produced by the bacterium to
      inactivate the two antibacterial effectors, thereby protecting its siblings from
      self-intoxication. Recently, Tse1-Tsi1 has been structurally characterized. Here,
      the structure of the Tse3-Tsi3 complex is reported at 1.9 A resolution. The
      results reveal that Tse3 contains a C-terminal catalytic domain that adopts a
      soluble lytic transglycosylase (SLT) fold in which three calcium-binding sites
      were surprisingly observed close to the catalytic Glu residue. The electrostatic
      properties of the substrate-binding groove are also distinctive from those of
      known structures with a similar fold. All of these features imply that a unique
      catalytic mechanism is utilized by Tse3 in cleaving glycosidic bonds. Tsi3
      comprises a single domain showing a beta-sandwich architecture that is
      reminiscent of the immunoglobulin fold. Three loops of Tsi3 insert deeply into
      the groove of Tse3 and completely occlude its active site, which forms the
      structural basis of Tse3 inactivation. This work is the first crystallographic
      report describing the three-dimensional structure of the Tse3-Tsi3 effector
      immunity pair. 

PMID- 24100310
TI  - A quality comparison of protein crystals grown under containerless conditions
      generated by diamagnetic levitation, silicone oil and agarose gel.
AB  - High-quality crystals are key to obtaining accurate three-dimensional structures
      of proteins using X-ray diffraction techniques. However, obtaining such protein
      crystals is often a challenge. Several containerless crystallization techniques
      have been reported to have the ability to improve crystal quality, but it is
      unknown which is the most favourable way to grow high-quality protein crystals.
      In this paper, a quality comparison of protein crystals which were grown under
      three containerless conditions provided by diamagnetic levitation, silicone oil
      and agarose gel was conducted. A control experiment on a vessel wall was also
      simultaneously carried out. Seven different proteins were crystallized under the
      four conditions, and the crystal quality was assessed in terms of the resolution
      limit, the mosaicity and the Rmerge. It was found that the crystals grown under
      the three containerless conditions demonstrated better morphology than those of
      the control. X-ray diffraction data indicated that the quality of the crystals
      grown under the three containerless conditions was better than that of the
      control. Of the three containerless crystallization techniques, the diamagnetic
      levitation technique exhibited the best performance in enhancing crystal quality.
      This paper is to our knowledge the first report of improvement of crystal quality
      using a diamagnetic levitation technique. Crystals obtained from agarose gel
      demonstrated the second best improvement in crystal quality. The study indicated
      that the diamagnetic levitation technique is indeed a favourable method for
      growing high-quality protein crystals, and its utilization is thus potentially
      useful in practical efforts to obtain well diffracting protein crystals. 

PMID- 24100311
TI  - Structure of the JmjC-domain-containing protein JMJD5.
AB  - The post-translational modification of histone tails is the principal process
      controlling epigenetic regulation in eukaryotes. The lysine methylation of
      histones is dynamically regulated by two distinct classes of enzymes:
      methyltransferases and demethylases. JMJD5, which plays an important role in cell
      cycle progression, circadian rhythms and embryonic cell proliferation, has been
      shown to be a JmjC-domain-containing histone demethylase with enzymatic activity
      towards H3K36me2. Here, the crystal structure of human JMJD5 lacking the N
      terminal 175 amino-acid residues is reported. The structure showed that the
      Gln275, Trp310 and Trp414 side chains might block the insertion of methylated
      lysine into the active centre of JMJD5, suppressing the histone demethylase
      activity of the truncated JMJD5 construct. A comparison of the structure of JMJD5
      with that of FIH, a well characterized protein hydroxylase, revealed that human
      JMJD5 might function as a protein hydroxylase. The interaction between JMJD5 and
      the core histone octamer proteins indicated that the histone proteins could be
      potential substrates for JMJD5. 

PMID- 24100312
TI  - On effective and optical resolutions of diffraction data sets.
AB  - In macromolecular X-ray crystallography, diffraction data sets are traditionally
      characterized by the highest resolution dhigh of the reflections that they
      contain. This measure is sensitive to individual reflections and does not refer
      to the eventual data incompleteness and anisotropy; it therefore does not
      describe the data well. A physically relevant and robust measure that provides a
      universal way to define the 'actual' effective resolution deff of a data set is
      introduced. This measure is based on the accurate calculation of the minimum
      distance between two immobile point scatterers resolved as separate peaks in the
      Fourier map calculated with a given set of reflections. This measure is
      applicable to any data set, whether complete or incomplete. It also allows
      characterizion of the anisotropy of diffraction data sets in which deff strongly
      depends on the direction. Describing mathematical objects, the effective
      resolution deff characterizes the 'geometry' of the set of measured reflections
      and is irrelevant to the diffraction intensities. At the same time, the
      diffraction intensities reflect the composition of the structure from physical
      entities: the atoms. The minimum distance for the atoms typical of a given
      structure is a measure that is different from and complementary to deff; it is
      also a characteristic that is complementary to conventional measures of the data
      set quality. Following the previously introduced terms, this value is called the
      optical resolution, dopt. The optical resolution as defined here describes the
      separation of the atomic images in the 'ideal' crystallographic Fourier map that
      would be calculated if the exact phases were known. The effective and optical
      resolution, as formally introduced in this work, are of general interest, giving
      a common 'ruler' for all kinds of crystallographic diffraction data sets. 

PMID- 24100314
TI  - A functional and structural study of the major metalloprotease secreted by the
      pathogenic fungus Aspergillus fumigatus.
AB  - Fungalysins are secreted fungal peptidases with the ability to degrade the
      extracellular matrix proteins elastin and collagen and are thought to act as
      virulence factors in diseases caused by fungi. Fungalysins constitute a unique
      family among zinc-dependent peptidases that bears low sequence similarity to
      known bacterial peptidases of the thermolysin family. The crystal structure of
      the archetype of the fungalysin family, Aspergillus fumigatus metalloprotease
      (AfuMep), has been obtained for the first time. The 1.8 A resolution structure of
      AfuMep corresponds to that of an autoproteolyzed proenzyme with separate
      polypeptide chains corresponding to the N-terminal prodomain in a binary complex
      with the C-terminal zinc-bound catalytic domain. The prodomain consists of a
      tandem of cystatin-like folds whose C-terminal end is buried into the active-site
      cleft of the catalytic domain. The catalytic domain harbouring the key catalytic
      zinc ion and its ligands, two histidines and one glutamic acid, undergoes a
      conspicuous rearrangement of its N-terminal end during maturation. One key
      positively charged amino-acid residue and the C-terminal disulfide bridge appear
      to contribute to its structural-functional properties. Thus, structural,
      biophysical and biochemical analysis were combined to provide a deeper
      comprehension of the underlying properties of A. fumigatus fungalysin, serving as
      a framework for the as yet poorly known metallopeptidases from pathogenic fungi. 

PMID- 24100313
TI  - Structural basis for the antibody neutralization of herpes simplex virus.
AB  - Glycoprotein D (gD) of herpes simplex virus (HSV) binds to a host cell surface
      receptor, which is required to trigger membrane fusion for virion entry into the
      host cell. gD has become a validated anti-HSV target for therapeutic antibody
      development. The highly inhibitory human monoclonal antibody E317 (mAb E317) was
      previously raised against HSV gD for viral neutralization. To understand the
      structural basis of antibody neutralization, crystals of the gD ectodomain bound
      to the E317 Fab domain were obtained. The structure of the complex reveals that
      E317 interacts with gD mainly through the heavy chain, which covers a large area
      for epitope recognition on gD, with a flexible N-terminal and C-terminal
      conformation. The epitope core structure maps to the external surface of gD,
      corresponding to the binding sites of two receptors, herpesvirus entry mediator
      (HVEM) and nectin-1, which mediate HSV infection. E317 directly recognizes the gD
      nectin-1 interface and occludes the HVEM contact site of gD to block its binding
      to either receptor. The binding of E317 to gD also prohibits the formation of the
      N-terminal hairpin of gD for HVEM recognition. The major E317-binding site on gD
      overlaps with either the nectin-1-binding residues or the neutralizing antigenic
      sites identified thus far (Tyr38, Asp215, Arg222 and Phe223). The epitopes of gD
      for E317 binding are highly conserved between two types of human herpesvirus (HSV
      1 and HSV-2). This study enables the virus-neutralizing epitopes to be correlated
      with the receptor-binding regions. The results further strengthen the previously
      demonstrated therapeutic and diagnostic potential of the E317 antibody.

PMID- 24100315
TI  - Structure of the polypeptide crotamine from the Brazilian rattlesnake Crotalus
      durissus terrificus.
AB  - The crystal structure of the myotoxic, cell-penetrating, basic polypeptide
      crotamine isolated from the venom of Crotalus durissus terrificus has been
      determined by single-wavelength anomalous dispersion techniques and refined at
      1.7 A resolution. The structure reveals distinct cationic and hydrophobic surface
      regions that are located on opposite sides of the molecule. This surface-charge
      distribution indicates its possible mode of interaction with negatively charged
      phospholipids and other molecular targets to account for its diverse
      pharmacological activities. Although the sequence identity between crotamine and
      human beta-defensins is low, the three-dimensional structures of these
      functionally related peptides are similar. Since crotamine is a leading member of
      a large family of myotoxic peptides, its structure will provide a basis for the
      design of novel cell-penetrating molecules. 

PMID- 24100316
TI  - Cross-protomer interaction with the photoactive site in oligomeric
      proteorhodopsin complexes.
AB  - Proteorhodopsins (PRs), members of the microbial rhodopsin superfamily of seven
      transmembrane-helix proteins that use retinal chromophores, comprise the largest
      subfamily of rhodopsins, yet very little structural information is available. PRs
      are ubiquitous throughout the biosphere and their genes have been sequenced in
      numerous species of bacteria. They have been shown to exhibit ion-pumping
      activity like their archaeal homolog bacteriorhodopsin (BR). Here, the first
      crystal structure of a proteorhodopsin, that of a blue-light-absorbing
      proteorhodopsin (BPR) isolated from the Mediterranean Sea at a depth of 12 m
      (Med12BPR), is reported. Six molecules of Med12BPR form a doughnut-shaped C6
      hexameric ring, unlike BR, which forms a trimer. Furthermore, the structures of
      two mutants of a related BPR isolated from the Pacific Ocean near Hawaii at a
      depth of 75 m (HOT75BPR), which show a C5 pentameric arrangement, are reported.
      In all three structures the retinal polyene chain is shifted towards helix C when
      compared with other microbial rhodopsins, and the putative proton-release group
      in BPR differs significantly from those of BR and xanthorhodopsin (XR). The most
      striking feature of proteorhodopsin is the position of the conserved active-site
      histidine (His75, also found in XR), which forms a hydrogen bond to the proton
      acceptor from the same molecule (Asp97) and also to Trp34 of a neighboring
      protomer. Trp34 may function by stabilizing His75 in a conformation that favors a
      deprotonated Asp97 in the dark state, and suggests cooperative behavior between
      protomers when the protein is in an oligomeric form. Mutation-induced alterations
      in proton transfers in the BPR photocycle in Escherichia coli cells provide
      evidence for a similar cross-protomer interaction of BPR in living cells and a
      functional role of the inter-protomer Trp34-His75 interaction in ion transport.
      Finally, Wat402, a key molecule responsible for proton translocation between the
      Schiff base and the proton acceptor in BR, appears to be absent in PR, suggesting
      that the ion-transfer mechanism may differ between PR and BR. 

PMID- 24100318
TI  - The DNA-binding domain of BenM reveals the structural basis for the recognition
      of a T-N11-A sequence motif by LysR-type transcriptional regulators.
AB  - LysR-type transcriptional regulators (LTTRs) play critical roles in metabolism
      and constitute the largest family of bacterial regulators. To understand protein
      DNA interactions, atomic structures of the DNA-binding domain and linker-helix
      regions of a prototypical LTTR, BenM, were determined by X-ray crystallography.
      BenM structures with and without bound DNA reveal a set of highly conserved amino
      acids that interact directly with DNA bases. At the N-terminal end of the
      recognition helix (alpha3) of a winged-helix-turn-helix DNA-binding motif,
      several residues create hydrophobic pockets (Pro30, Pro31 and Ser33). These
      pockets interact with the methyl groups of two thymines in the DNA-recognition
      motif and its complementary strand, T-N11-A. This motif usually includes some
      dyad symmetry, as exemplified by a sequence that binds two subunits of a BenM
      tetramer (ATAC-N7-GTAT). Gln29 forms hydrogen bonds to adenine in the first
      position of the recognition half-site (ATAC). Another hydrophobic pocket defined
      by Ala28, Pro30 and Pro31 interacts with the methyl group of thymine,
      complementary to the base at the third position of the half-site. Arg34 interacts
      with the complementary base of the 3' position. Arg53, in the wing, provides AT
      tract recognition in the minor groove. For DNA recognition, LTTRs use highly
      conserved interactions between amino acids and nucleotide bases as well as
      numerous less-conserved secondary interactions. 

PMID- 24100317
TI  - Rv2969c, essential for optimal growth in Mycobacterium tuberculosis, is a DsbA
      like enzyme that interacts with VKOR-derived peptides and has atypical features
      of DsbA-like disulfide oxidases.
AB  - The bacterial disulfide machinery is an attractive molecular target for
      developing new antibacterials because it is required for the production of
      multiple virulence factors. The archetypal disulfide oxidase proteins in
      Escherichia coli (Ec) are DsbA and DsbB, which together form a functional unit:
      DsbA introduces disulfides into folding proteins and DsbB reoxidizes DsbA to
      maintain it in the active form. In Mycobacterium tuberculosis (Mtb), no DsbB
      homologue is encoded but a functionally similar but structurally divergent
      protein, MtbVKOR, has been identified. Here, the Mtb protein Rv2969c is
      investigated and it is shown that it is the DsbA-like partner protein of MtbVKOR.
      It is found that it has the characteristic redox features of a DsbA-like protein:
      a highly acidic catalytic cysteine, a highly oxidizing potential and a
      destabilizing active-site disulfide bond. Rv2969c also has peptide-oxidizing
      activity and recognizes peptide segments derived from the periplasmic loops of
      MtbVKOR. Unlike the archetypal EcDsbA enzyme, Rv2969c has little or no activity
      in disulfide-reducing and disulfide-isomerase assays. The crystal structure of
      Rv2969c reveals a canonical DsbA fold comprising a thioredoxin domain with an
      embedded helical domain. However, Rv2969c diverges considerably from other DsbAs,
      including having an additional C-terminal helix (H8) that may restrain the
      mobility of the catalytic helix H1. The enzyme is also characterized by a very
      shallow hydrophobic binding surface and a negative electrostatic surface
      potential surrounding the catalytic cysteine. The structure of Rv2969c was also
      used to model the structure of a paralogous DsbA-like domain of the Ser/Thr
      protein kinase PknE. Together, these results show that Rv2969c is a DsbA-like
      protein with unique properties and a limited substrate-binding specificity. 

PMID- 24100319
TI  - High-resolution structure of an atypical alpha-phosphoglucomutase related to
      eukaryotic phosphomannomutases.
AB  - The first structure of a bacterial alpha-phosphoglucomutase with an overall fold
      similar to eukaryotic phosphomannomutases is reported. Unlike most alpha
      phosphoglucomutases within the alpha-D-phosphohexomutase superfamily, it belongs
      to subclass IIb of the haloacid dehalogenase superfamily (HADSF). It catalyzes
      the reversible conversion of alpha-glucose 1-phosphate to glucose 6-phosphate.
      The crystal structure of alpha-phosphoglucomutase from Lactococcus lactis (APGM)
      was determined at 1.5 A resolution and contains a sulfate and a glycerol bound at
      the enzyme active site that partially mimic the substrate. A dimeric form of APGM
      is present in the crystal and in solution, an arrangement that may be
      functionally relevant. The catalytic mechanism of APGM and its strict specificity
      towards alpha-glucose 1-phosphate are discussed. 

PMID- 24100320
TI  - High-resolution structure of a papaya plant-defense barwin-like protein solved by
      in-house sulfur-SAD phasing.
AB  - The first crystal structure of a barwin-like protein, named carwin, has been
      determined at high resolution by single-wavelength anomalous diffraction (SAD)
      phasing using the six intrinsic S atoms present in the protein. The barwin-like
      protein was purified from Carica papaya latex and crystallized in the
      orthorhombic space group P212121. Using in-house Cu Kalpha X-ray radiation, 16
      cumulative diffraction data sets were acquired to increase the signal-to-noise
      level and thereby the anomalous scattering signal. A sequence-database search on
      the papaya genome identified two carwin isoforms of 122 residues in length, both
      containing six S atoms that yield an estimated Bijvoet ratio of 0.93% at 1.54 A
      wavelength. A systematic analysis of data quality and redundancy was performed to
      assess the capacity to locate the S atoms and to phase the data. It was observed
      that the crystal decay was low during data collection and that successful S-SAD
      phasing could be obtained with a relatively low data multiplicity of about 7.
      Using a synchrotron source, high-resolution data (1 A) were collected from two
      different crystal forms of the papaya latex carwin. The refined structures showed
      a central beta-barrel of six strands surrounded by several alpha-helices and
      loops. The beta-barrel of carwin appears to be a common structural module that is
      shared within several other unrelated proteins. Finally, the possible biological
      function of the protein is discussed. 

PMID- 24100321
TI  - The structure of a glycoside hydrolase family 81 endo-beta-1,3-glucanase.
AB  - Endo-beta-1,3-glucanases catalyze the hydrolysis of beta-1,3-glycosidic linkages
      in glucans. They are also responsible for rather diverse physiological functions
      such as carbon utilization, cell-wall organization and pathogen defence.
      Glycoside hydrolase (GH) family 81 mainly consists of beta-1,3-glucanases from
      fungi, higher plants and bacteria. A novel GH family 81 beta-1,3-glucanase gene
      (RmLam81A) from Rhizomucor miehei was expressed in Escherichia coli. Purified
      RmLam81A was crystallized and the structure was determined in two crystal forms
      (form I-free and form II-Se) at 2.3 and 2.0 A resolution, respectively. Here, the
      crystal structure of a member of GH family 81 is reported for the first time. The
      structure of RmLam81A is greatly different from all endo-beta-1,3-glucanase
      structures available in the Protein Data Bank. The overall structure of the
      RmLam81A monomer consists of an N-terminal beta-sandwich domain, a C-terminal
      (alpha/alpha)6 domain and an additional domain between them. Glu553 and Glu557
      are proposed to serve as the proton donor and basic catalyst, respectively, in a
      single-displacement mechanism. In addition, Tyr386, Tyr482 and Ser554 possibly
      contribute to both the position or the ionization state of the basic catalyst
      Glu557. The first crystal structure of a GH family 81 member will be helpful in
      the study of the GH family 81 proteins and endo-beta-1,3-glucanases. 

PMID- 24100322
TI  - Improving experimental phases for strong reflections prior to density
      modification.
AB  - Experimental phasing of diffraction data from macromolecular crystals involves
      deriving phase probability distributions. These distributions are often bimodal,
      making their weighted average, the centroid phase, improbable, so that electron
      density maps computed using centroid phases are often non-interpretable. Density
      modification brings in information about the characteristics of electron density
      in protein crystals. In successful cases, this allows a choice between the modes
      in the phase probability distributions, and the maps can cross the borderline
      between non-interpretable and interpretable. Based on the suggestions by Vekhter
      [Vekhter (2005), Acta Cryst. D61, 899-902], the impact of identifying optimized
      phases for a small number of strong reflections prior to the density-modification
      process was investigated while using the centroid phase as a starting point for
      the remaining reflections. A genetic algorithm was developed that optimizes the
      quality of such phases using the skewness of the density map as a target
      function. Phases optimized in this way are then used in density modification. In
      most of the tests, the resulting maps were of higher quality than maps generated
      from the original centroid phases. In one of the test cases, the new method
      sufficiently improved a marginal set of experimental SAD phases to enable
      successful map interpretation. A computer program, SISA, has been developed to
      apply this method for phase improvement in macromolecular crystallography. 

PMID- 24100323
TI  - Structural characterization of gephyrin by AFM and SAXS reveals a mixture of
      compact and extended states.
AB  - Gephyrin is a trimeric protein involved in the final steps of molybdenum-cofactor
      (Moco) biosynthesis and in the clustering of inhibitory glycine and GABAA
      receptors at postsynaptic specializations. Each protomer consists of stably
      folded domains (referred to as the G and E domains) located at either terminus
      and connected by a proteolytically sensitive linker of ~150 residues. Both
      terminal domains can oligomerize in their isolated forms; however, in the context
      of the full-length protein only the G-domain trimer is permanently present,
      whereas E-domain dimerization is prevented. Atomic force microscopy (AFM) and
      small-angle X-ray scattering (SAXS) reveal a high degree of flexibility in the
      structure of gephyrin. The results imply an equilibrium between compact and
      extended conformational states in solution, with a preference for compact states.
      CD spectroscopy suggests that a partial compaction is achieved by interactions of
      the linker with the G and E domains. Taken together, the data provide a rationale
      for the role of the linker in the overall structure and the conformational
      dynamics of gephyrin. 

PMID- 24100325
TI  - Determination of the GH3.12 protein conformation through HPLC-integrated SAXS
      measurements combined with X-ray crystallography.
AB  - The combination of protein crystallography and small-angle X-ray scattering
      (SAXS) provides a powerful method to investigate changes in protein conformation.
      These complementary structural techniques were used to probe the solution
      structure of the apo and the ligand-bound forms of the Arabidopsis thaliana acyl
      acid-amido synthetase GH3.12. This enzyme is part of the extensive GH3 family and
      plays a critical role in the regulation of plant hormones through the formation
      of amino-acid-conjugated hormone products via an ATP-dependent reaction
      mechanism. The enzyme adopts two distinct C-terminal domain orientations with
      'open' and 'closed' active sites. Previous studies suggested that ATP only binds
      in the open orientation. Here, the X-ray crystal structure of GH3.12 is presented
      in the closed conformation in complex with the nonhydrolysable ATP analogue
      AMPCPP and the substrate salicylate. Using on-line HPLC purification combined
      with SAXS measurements, the most likely apo and ATP-bound protein conformations
      in solution were determined. These studies demonstrate that the C-terminal domain
      is flexible in the apo form and favours the closed conformation upon ATP binding.
      In addition, these data illustrate the efficacy of on-line HPLC purification
      integrated into the SAXS sample-handling environment to reliably monitor small
      changes in protein conformation through the collection of aggregate-free and
      highly redundant data. 

PMID- 24100324
TI  - Structure of fully liganded Hb zeta2beta2s trapped in a tense conformation.
AB  - A variant Hb zeta2beta2(s) that is formed from sickle hemoglobin (Hb S;
      alpha2beta2(s)) by exchanging adult alpha-globin with embryonic zeta-globin
      subunits shows promise as a therapeutic agent for sickle-cell disease (SCD). Hb
      zeta2beta2(s) inhibits the polymerization of deoxygenated Hb S in vitro and
      reverses characteristic features of SCD in vivo in mouse models of the disorder.
      When compared with either Hb S or with normal human adult Hb A (alpha2beta2), Hb
      zeta2beta2(s) exhibits atypical properties that include a high oxygen affinity,
      reduced cooperativity, a weak Bohr effect and blunted 2,3-diphosphoglycerate
      allostery. Here, the 1.95 A resolution crystal structure of human Hb
      zeta2beta2(s) that was expressed in complex transgenic knockout mice and purified
      from their erythrocytes is presented. When fully liganded with carbon monoxide,
      Hb zeta2beta2(s) displays a central water cavity, a zeta1-beta(s)2 (or zeta2
      beta(s)1) interface, intersubunit salt-bridge/hydrogen-bond interactions, C
      terminal betaHis146 salt-bridge interactions, and a beta-cleft, that are highly
      unusual for a relaxed hemoglobin structure and are more typical of a tense
      conformation. These quaternary tense-like features contrast with the tertiary
      relaxed-like conformations of the zeta1beta(s)1 dimer and the CD and FG corners,
      as well as the overall structures of the heme cavities. This crystallographic
      study provides insights into the altered oxygen-transport properties of Hb
      zeta2beta2(s) and, moreover, decouples tertiary- and quaternary-structural events
      that are critical to Hb ligand binding and allosteric function. 

PMID- 24100326
TI  - Structure of the Sgt2 dimerization domain complexed with the Get5 UBL domain
      involved in the targeting of tail-anchored membrane proteins to the endoplasmic
      reticulum.
AB  - The insertion of tail-anchored membrane (TA) proteins into the appropriate
      membrane is a post-translational event that requires stabilization of the
      transmembrane domain and targeting to the proper destination. Sgt2, a small
      glutamine-rich tetratricopeptide-repeat protein, is a heat-shock protein cognate
      (HSC) co-chaperone that preferentially binds endoplasmic reticulum-destined TA
      proteins and directs them to the GET pathway via Get4 and Get5. The N-terminal
      domain of Sgt2 seems to exert dual functions. It mediates Get5 interaction and
      allows substrate delivery to Get3. Following the N-terminus of Get5 is a
      ubiquitin-like (Ubl) domain that interacts with the N-terminus of Sgt2. Here, the
      crystal structure of the Sgt2 dimerization domain complexed with the Get5 Ubl
      domain (Sgt2N-Get5Ubl) is reported. This complex reveals an intimate interaction
      between one Sgt2 dimer and one Get5 monomer. This research further demonstrates
      that hydrophobic residues from both Sgt2 and Get5 play an important role in cell
      survival under heat stress. This study provides detailed molecular insights into
      the specific binding of this GET-pathway complex. 

PMID- 24100327
TI  - Structures of the Porphyromonas gingivalis OxyR regulatory domain explain
      differences in expression of the OxyR regulon in Escherichia coli and P.
      gingivalis.
AB  - OxyR transcriptionally regulates Escherichia coli oxidative stress response genes
      through a reversibly reducible cysteine disulfide biosensor of cellular redox
      status. Structural changes induced by redox changes in these cysteines are
      conformationally transmitted to the dimer subunit interfaces, which alters dimer
      and tetramer interactions with DNA. In contrast to E. coli OxyR regulatory-domain
      structures, crystal structures of Porphyromonas gingivalis OxyR regulatory
      domains show minimal differences in dimer configuration on changes in cysteine
      disulfide redox status. This locked configuration of the P. gingivalis OxyR
      regulatory-domain dimer closely resembles the oxidized (activating) form of the
      E. coli OxyR regulatory-domain dimer. It correlates with the observed
      constitutive activation of some oxidative stress genes in P. gingivalis and is
      attributable to a single amino-acid insertion in P. gingivalis OxyR relative to
      E. coli OxyR. Modelling of full-length P. gingivalis, E. coli and Neisseria
      meningitidis OxyR-DNA complexes predicts different modes of DNA binding for the
      reduced and oxidized forms of each. 

PMID- 24100328
TI  - Structure of a bifunctional alcohol dehydrogenase involved in bioethanol
      generation in Geobacillus thermoglucosidasius.
AB  - Bifunctional alcohol/aldehyde dehydrogenase (ADHE) enzymes are found within many
      fermentative microorganisms. They catalyse the conversion of an acyl-coenzyme A
      to an alcohol via an aldehyde intermediate; this is coupled to the oxidation of
      two NADH molecules to maintain the NAD(+) pool during fermentative metabolism.
      The structure of the alcohol dehydrogenase (ADH) domain of an ADHE protein from
      the ethanol-producing thermophile Geobacillus thermoglucosidasius has been
      determined to 2.5 A resolution. This is the first structure to be reported for
      such a domain. In silico modelling has been carried out to generate a homology
      model of the aldehyde dehydrogenase domain, and this was subsequently docked with
      the ADH-domain structure to model the structure of the complete ADHE protein.
      This model suggests, for the first time, a structural mechanism for the formation
      of the large multimeric assemblies or 'spirosomes' that are observed for this
      ADHE protein and which have previously been reported for ADHEs from other
      organisms. 

PMID- 24100329
TI  - Three-dimensional domain swapping and supramolecular protein assembly: insights
      from the X-ray structure of a dimeric swapped variant of human pancreatic RNase.
AB  - The deletion of five residues in the loop connecting the N-terminal helix to the
      core of monomeric human pancreatic ribonuclease leads to the formation of an
      enzymatically active domain-swapped dimer (desHP). The crystal structure of desHP
      reveals the generation of an intriguing fibril-like aggregate of desHP molecules
      that extends along the c crystallographic axis. Dimers are formed by three
      dimensional domain swapping. Tetramers are formed by the aggregation of swapped
      dimers with slightly different quaternary structures. The tetramers interact in
      such a way as to form an infinite rod-like structure that propagates throughout
      the crystal. The observed supramolecular assembly captured in the crystal
      predicts that desHP fibrils could form in solution; this has been confirmed by
      atomic force microscopy. These results provide new evidence that three
      dimensional domain swapping can be a mechanism for the formation of elaborate
      large assemblies in which the protein, apart from the swapping, retains its
      original fold. 

PMID- 24100330
TI  - Structural analysis and insights into the glycon specificity of the rice GH1
      Os7BGlu26 beta-D-mannosidase.
AB  - Rice Os7BGlu26 is a GH1 family glycoside hydrolase with a threefold higher
      kcat/Km value for 4-nitrophenyl beta-D-mannoside (4NPMan) compared with 4
      nitrophenyl beta-D-glucoside (4NPGlc). To investigate its selectivity for beta-D
      mannoside and beta-D-glucoside substrates, the structures of apo Os7BGlu26 at a
      resolution of 2.20 A and of Os7BGlu26 with mannose at a resolution of 2.45 A were
      elucidated from isomorphous crystals in space group P212121. The (beta/alpha)8
      barrel structure is similar to other GH1 family structures, but with a narrower
      active-site cleft. The Os7BGlu26 structure with D-mannose corresponds to a
      product complex, with beta-D-mannose in the (1)S5 skew-boat conformation. Docking
      of the (1)S3, (1)S5, (2)SO and (3)S1 pyranose-ring conformations of 4NPMan and
      4NPGlc substrates into the active site of Os7BGlu26 indicated that the lowest
      energies were in the (1)S5 and (1)S3 skew-boat conformations. Comparison of these
      docked conformers with other rice GH1 structures revealed differences in the
      residues interacting with the catalytic acid/base between enzymes with and
      without beta-D-mannosidase activity. The mutation of Tyr134 to Trp in Os7BGlu26
      resulted in similar kcat/Km values for 4NPMan and 4NPGlc, while mutation of
      Tyr134 to Phe resulted in a 37-fold higher kcat/Km for 4NPMan than 4NPGlc.
      Mutation of Cys182 to Thr decreased both the activity and the selectivity for
      beta-D-mannoside. It was concluded that interactions with the catalytic acid/base
      play a significant role in glycon selection. 

PMID- 24100331
TI  - Conformational changes in human prolyl-tRNA synthetase upon binding of the
      substrates proline and ATP and the inhibitor halofuginone.
AB  - Aminoacyl-tRNA synthetases recognize cognate amino acids and tRNAs from their
      noncognate counterparts and catalyze the formation of aminoacyl-tRNAs.
      Halofuginone (HF), a coccidiostat used in veterinary medicine, exerts its effects
      by acting as a high-affinity inhibitor of the enzyme glutamyl-prolyl-tRNA
      synthetase (EPRS). In order to elucidate the precise molecular basis of this
      inhibition mechanism of human EPRS, the crystal structures of the prolyl-tRNA
      synthetase domain of human EPRS (hPRS) at 2.4 A resolution (hPRS-apo), of hPRS
      complexed with ATP and the substrate proline at 2.3 A resolution (hPRS-sub) and
      of hPRS complexed with HF at 2.62 A resolution (hPRS-HF) are presented. These
      structures show plainly that motif 1 functions as a cap in hPRS, which is loosely
      opened in hPRS-apo, tightly closed in hPRS-sub and incorrectly closed in hPRS-HF.
      In addition, the structural analyses are consistent with more effective binding
      of hPRS to HF with ATP. Mutagenesis and biochemical analysis confirmed the key
      roles of two residues, Phe1097 and Arg1152, in the HF inhibition mechanism. These
      structures will lead to the development of more potent and selective hPRS
      inhibitors for promoting inflammatory resolution. 

PMID- 24100333
TI  - The IMAGINE instrument: first neutron protein structure and new capabilities for
      neutron macromolecular crystallography.
AB  - The first high-resolution neutron protein structure of perdeuterated rubredoxin
      from Pyrococcus furiosus (PfRd) determined using the new IMAGINE macromolecular
      neutron crystallography instrument at the Oak Ridge National Laboratory is
      reported. Neutron diffraction data extending to 1.65 A resolution were collected
      from a relatively small 0.7 mm(3) PfRd crystal using 2.5 d (60 h) of beam time.
      The refined structure contains 371 out of 391, or 95%, of the D atoms of the
      protein and 58 solvent molecules. The IMAGINE instrument is designed to provide
      neutron data at or near atomic resolution (1.5 A) from crystals with volume <1.0
      mm(3) and with unit-cell edges <100 A. Beamline features include novel elliptical
      focusing mirrors that deliver neutrons into a 2.0 * 3.2 mm focal spot at the
      sample position with full-width vertical and horizontal divergences of 0.5 and
      0.6 degrees , respectively. Variable short- and long-wavelength cutoff optics
      provide automated exchange between multiple-wavelength configurations (lambdamin
      = 2.0, 2.8, 3.3 A to lambdamax = 3.0, 4.0, 4.5, ~20 A). These optics produce a
      more than 20-fold increase in the flux density at the sample and should help to
      enable more routine collection of high-resolution data from submillimetre-cubed
      crystals. Notably, the crystal used to collect these PfRd data was 5-10 times
      smaller than those previously reported. 

PMID- 24100332
TI  - Structures of oncogenic, suppressor and rescued p53 core-domain variants:
      mechanisms of mutant p53 rescue.
AB  - To gain insights into the mechanisms by which certain second-site suppressor
      mutations rescue the function of a significant number of cancer mutations of the
      tumor suppressor protein p53, X-ray crystallographic structures of four p53 core
      domain variants were determined. These include an oncogenic mutant, V157F, two
      single-site suppressor mutants, N235K and N239Y, and the rescued cancer mutant
      V157F/N235K/N239Y. The V157F mutation substitutes a smaller hydrophobic valine
      with a larger hydrophobic phenylalanine within strand S4 of the hydrophobic core.
      The structure of this cancer mutant shows no gross structural changes in the
      overall fold of the p53 core domain, only minor rearrangements of side chains
      within the hydrophobic core of the protein. Based on biochemical analysis, these
      small local perturbations induce instability in the protein, increasing the free
      energy by 3.6 kcal mol(-1) (15.1 kJ mol(-1)). Further biochemical evidence shows
      that each suppressor mutation, N235K or N239Y, acts individually to restore
      thermodynamic stability to V157F and that both together are more effective than
      either alone. All rescued mutants were found to have wild-type DNA-binding
      activity when assessed at a permissive temperature, thus pointing to
      thermodynamic stability as the critical underlying variable. Interestingly,
      thermodynamic analysis shows that while N239Y demonstrates stabilization of the
      wild-type p53 core domain, N235K does not. These observations suggest distinct
      structural mechanisms of rescue. A new salt bridge between Lys235 and Glu198,
      found in both the N235K and rescued cancer mutant structures, suggests a rescue
      mechanism that relies on stabilizing the beta-sandwich scaffold. On the other
      hand, the substitution N239Y creates an advantageous hydrophobic contact between
      the aromatic ring of this tyrosine and the adjacent Leu137. Surprisingly, the
      rescued cancer mutant shows much larger structural deviations than the cancer
      mutant alone when compared with wild-type p53. These suppressor mutations appear
      to rescue p53 function by creating novel intradomain interactions that stabilize
      the core domain, allowing compensation for the destabilizing V157F mutation. 

PMID- 24100334
TI  - Different orientations of low-molecular-weight fragments in the binding pocket of
      a BRD4 bromodomain.
AB  - Bromodomains are involved in the regulation of chromatin architecture and
      transcription through the recognition of acetylated lysines in histones and other
      proteins. Many of them are considered to be relevant pharmacological targets for
      different pathologies. Three crystallographic structures of the N-terminal
      bromodomain of BRD4 in complex with low-molecular-weight fragments are presented.
      They show that similar molecules mimicking acetylated lysine bind the bromodomain
      with different orientations and exploit different interactions. It is also
      advised to avoid DMSO when searching for low-affinity fragments that interact
      with bromodomains since DMSO binds in the acetylated lysine-recognition pocket of
      BRD4. 

PMID- 24100335
TI  - Integrating the evidence for single-incision laparoscopic cholecystectomy: is it
      "looking" good?

PMID- 24100336
TI  - Metabolic syndrome is less likely to resolve in Hispanics and non-Hispanic blacks
      after bariatric surgery.
AB  - OBJECTIVE: To determine predictors of metabolic syndrome and its resolution in a
      large, ethnically diverse adult population undergoing bariatric surgery.
      BACKGROUND: There is still limited knowledge about the impact of bariatric
      surgery on chronic health conditions such as metabolic syndrome. METHODS: Adults
      having had a laparoscopic Roux-en-Y gastric bypass or a laparoscopic vertical
      sleeve gastrectomy between 2007 and 2009 (n = 4088) without revision during the
      study period of January 1, 2007 through December 31, 2011 were eligible for the
      study. Diagnosis and resolution of metabolic syndrome were determined using
      standard criteria with electronic medical records of laboratory, diagnosis, and
      pharmacy information. RESULTS: Patients were primarily women (82%), non-Hispanic
      black (17%) or Hispanic (32%), 45 +/- 11 years old, and had a body mass index
      (BMI) of 47.10 +/- 7.73 kg/m at the time of surgery. After multivariate
      adjustment, metabolic syndrome was less likely to resolve in patients if they had
      a laparoscopic vertical sleeve gastrectomy procedure and a higher BMI at surgery,
      were older, were male or were either Hispanic or non-Hispanic black. The effects
      of age, race/ethnicity, and BMI at the time of surgery remained after accounting
      for weight loss. CONCLUSIONS: On the basis of our findings, bariatric surgery may
      be most effective for younger, less obese patients who are early in the course of
      their cardiometabolic disease. Future research should investigate the factors
      that lead to lower rates of disease resolution after bariatric surgery for
      racial/ethnic minority groups.

PMID- 24100337
TI  - Hydroxyethyl starch reduces coagulation competence and increases blood loss
      during major surgery: results from a randomized controlled trial.
AB  - OBJECTIVE: This study evaluated whether administration of hydroxyethyl starch
      (HES) 130/0.4 affects coagulation competence and influences the perioperative
      blood loss. BACKGROUND: Artificial colloids substitute blood volume during
      surgery; with the administration of HES 130/0.4 (Voluven, Fresenius Kabi,
      Uppsala, Sweden) only a minor effect on coagulation competence is expected.
      METHODS: Eighty patients were scanned for enrollment in the study, and 40
      patients fulfilled the inclusion criteria. Two patients withdrew their consent to
      participate in the study, and 5 patients were excluded. Thus, 16 patients were
      randomized to receive lactated Ringer's solution and 17 to receive HES 130/0.4.
      RESULTS: Among the patients receiving HES 130/0.4, thrombelastography indicated
      reduced clot strength (P < 0.001) and blinded evaluation of the perioperative
      blood loss was 2.2 (range 0.5 to 5.0) versus 1.4 (range 0.5 to 2.4) L in the
      patients who received HES 130/0.4 or lactated Ringer, respectively (P < 0.038).
      The patients in the lactated Ringer's group, however, received more fluid (P <
      0.0001) than those in the HES 130/0.4 group. There was no significant difference
      between the 2 groups with regard to frequency of reoperations or the length of
      hospital stay, but use of HES 130/0.4 was both more expensive and less
      efficacious than the use of lactated Ringer. CONCLUSIONS: Administration of HES
      130/0.4 reduced clot strength and perioperative hemorrhage increased by more than
      50%, while administration of lactated Ringer's solution provoked an approximately
      2.5 times greater positive volume balance at the end of surgery.

PMID- 24100338
TI  - The clinical utility of the combination of T stage and venous invasion to predict
      survival in patients undergoing surgery for colorectal cancer.
AB  - OBJECTIVE: To examine the clinical utility of improved detection of venous
      invasion (VI) in patients undergoing potentially curative resection of colorectal
      cancer. BACKGROUND: VI is a feature of colorectal cancer (CRC) progression.
      Elastica staining can be used to improve detection of VI and correspondingly its
      prediction of patient survival. METHODS: A single-center, observational study of
      pathology variables, including detection of VI by staining for elastica, using
      631 stage I to III CRC specimens, collected from 1997 to 2009 (176 analyzed
      retrospectively and 455 analyzed prospectively), was performed. RESULTS: VI was
      detected in 56% of patients with CRC. Over a median follow-up period of 73
      months, 238 patients died (134 from cancer). On multivariate analysis, VI by
      elastica staining was associated with a shorter survival duration, independent of
      other pathology features, in all cases [hazard ratio (HR) = 3.94, 95% confidence
      interval (CI): 2.33-6.65, P < 0.001] and in node-negative cases (HR = 3.55, 95%
      CI: 1.81-6.97; P < 0.001). In the absence of elastica-detected VI, with the
      exception of T stage, no other pathology features were associated with survival
      time. Therefore, the combination of T stage and VI (TVI) on survival was
      examined. Five-year cancer mortality could be stratified between 100% and 54% for
      patients with node-negative tumors and between 100% and 33% for patients with
      node-positive tumors. In all cases, the TVI had similar predictive value as that
      of T stage and node status (TNM). In node-negative disease, TVI had superior
      predictive value. CONCLUSIONS: The results of the present study have prompted the
      development of a novel tumor staging system based on TVI. The TVI has clinical
      utility, especially in node-negative disease, in predicting outcome following
      curative resection for CRC.

PMID- 24100339
TI  - A systematic review of surgical skills transfer after simulation-based training:
      laparoscopic cholecystectomy and endoscopy.
AB  - OBJECTIVE: A systematic review to determine whether skills acquired through
      simulation-based training transfer to the operating room for the procedures of
      laparoscopic cholecystectomy and endoscopy. BACKGROUND: Simulation-based training
      assumes that skills are directly transferable to the operation room, but only a
      few studies have investigated the effect of simulation-based training on surgical
      performance. METHODS: A systematic search strategy that was used in 2006 was
      updated to retrieve relevant studies. Inclusion of articles was determined using
      a predetermined protocol, independent assessment by 2 reviewers, and a final
      consensus decision. RESULTS: Seventeen randomized controlled trials and 3
      nonrandomized comparative studies were included in this review. In most cases,
      simulation-based training was in addition to patient-based training programs.
      Only 2 studies directly compared simulation-based training in isolation with
      patient-based training. For laparoscopic cholecystectomy (n = 10 studies) and
      endoscopy (n = 10 studies), participants who reached simulation-based skills
      proficiency before undergoing patient-based assessment performed with higher
      global assessment scores and fewer errors in the operating room than their
      counterparts who did not receive simulation training. Not all parameters measured
      were improved. Two of the endoscopic studies compared simulation-based training
      in isolation with patient-based training with different results: for
      sigmoidoscopy, patient-based training was more effective, whereas for
      colonoscopy, simulation-based training was equally effective. CONCLUSIONS: Skills
      acquired by simulation-based training seem to be transferable to the operative
      setting for laparoscopic cholecystectomy and endoscopy. Future research will
      strengthen these conclusions by evaluating predetermined competency levels on the
      same simulators and using objective validated global rating scales to measure
      operative performance.

PMID- 24100340
TI  - Reply to letter: "identifying important predictors for anastomotic leak after
      colon and rectal resection: prospective study on 616 patients".

PMID- 24100341
TI  - Reply to letter: "Questions about branch-duct IPMNs with Sendai-negative
      criteria".

PMID- 24100342
TI  - Reply to letter: "Surgery for small and asymptomatic branch-duct IPMNs".

PMID- 24100344
TI  - Free energies of (Co, Fe, Ni, Zn)Fe2O4 spinels and oxides in water at high
      temperatures and pressure from density functional theory: results for
      stoichiometric NiO and NiFe2O4 surfaces.
AB  - A set of effective chemical potentials (ECPs) are derived that connect energies
      of (Co, Fe, Ni, Zn)Fe2O4 spinels and oxides calculated at 0 K from density
      functional theory (DFT) to free energies in high temperature and pressure water.
      The ECPs are derived and validated by solving a system of linear equations that
      combine DFT and experimental free energies for NiO, ZnO, Fe2O3, Fe3O4, FeO(OH),
      CoFe2O4, ZnFe2O4, NiFe2O4 and H2O. To connect to solution phase chemistry, a set
      of ECPs are also derived for solvated Ni(2+), Zn(2+), Fe(2+) and Fe(3+) ions
      using an analogous set of linear equations and the solid ECPs. The ECPs are used
      to calculate free energies of low index stoichiometric surfaces of nickel oxide
      (NiO) and nickel ferrite (NiFe2O4) in water as a function of temperature from 300
      to 600 K at a pressure of 155 bar. Surface denuding at high temperatures is
      predicted, the implications of which for the formation of oxide corrosion
      products on heat transfer surfaces in light-water nuclear reactors are discussed.

PMID- 24100343
TI  - M-CSF cooperating with NFkappaB induces macrophage transformation from M1 to M2
      by upregulating c-Jun.
AB  - Increasing evidence suggests tumor-associated macrophages (TAMs) are polarized M2
      subtype of macrophage that exerts pro-tumor effects and promote the malignancy of
      some cancers, but the concrete mechanism is not well defined. Our previous
      research exhibited that proto-oncogene AP-1 regulated IL-6 expression in
      macrophages and promoted the formation of M2 macrophages. In this study, we
      investigate whether extra-cellular stimulus M-CSF help this process or nuclear
      factor NFkappaB has a synergistic role in the activation state of polarized M2
      subtype of macrophage. RAW 264.7 macrophage and 4T1 mouse breast cancer cells
      were co-cultured to reconstruct tumor microenvironment. Being co-cultured with
      4T1 or its supernatant, the expression of c-Jun, the member of AP-1 family, has a
      dramatically increase both on the level of gene and on the protein in RAW 264.7
      macrophages, but the expression of c-Fos does not increase neither on the level
      of gene nor on the protein. After co-cultured with 4T1, RAW 264.7 has a higher
      consumption of M-CSF than RAW 264.7 macrophages alone. With the stimulation of M
      CSF, the mRNA of c-Jun increased significantly, but decreased remarkably after
      adding the anti-M-CSF. And at the same time, p50, the member of NFkappaB family,
      has a similar tendency to c-Jun. WB results suggest that with the stimulation of
      M-CSF, p-Jun in nuclear increases heavily but decreases after the neutralizing
      antibody added. Coimmunoprecipitation and immunoblotting techniques confirmed
      that c-Jun and p50 NFkappaB coprecipitated, and c-Jun protein expression is
      properly enhanced with rM-CSF effect. In conclusion, M-CSF induces macrophage
      transformation by upregulating c-Jun with a certain synergy of NFkappaB. Our
      study may present a novel therapeutic strategy against cancer. 

PMID- 24100345
TI  - Current status of gene therapy for cancer.
AB  - PURPOSE OF REVIEW: In recent years, remarkable progress has been made in the
      development of cancer gene therapy into an applicable treatment modality for
      immunogene, suicide, gene correction and oncolytic therapies. New exciting
      developments for gene suppression or miRNA therapies are under way. The efforts
      are focused on more efficient and specific attack at known and novel targets,
      improvement of vector delivery and therapeutic efficacy. In this review,
      promising and new gene therapy approaches and clinical studies are briefly
      discussed to highlight important future directions of preclinical and clinical
      efforts. RECENT FINDINGS: Apart from progress for vector development and even
      more important, improvements for suicide, T-cell-based, oncolytic virus therapies
      were achieved. In addition, new emerging therapies are successfully developed,
      which are particularly promising for siRNA-based technologies applied to gene
      suppression therapy. Novel approaches, such as transcription factor ODN-based
      decoy, complement the spectrum of current cancer gene therapy. SUMMARY: In
      summary, cancer gene therapy has made remarkable progress in the
      improvement/refinement of existing strategies and delivery systems. The field is
      moving toward a therapeutic option, which will also be applicable for the
      treatment of disseminated metastases. Furthermore, numerous new approaches are
      about to be translated in clinical trials.

PMID- 24100346
TI  - Targeting receptor tyrosine kinases in  HER2-negative breast cancer.
AB  - PURPOSE OF REVIEW: The targeting of receptor tyrosine kinases (RTKs) has been a
      major area for breast cancer therapy, exemplified by the targeting of HER2
      amplified breast cancer. RECENT FINDINGS: We review the data on the activation of
      RTKs in HER2-negative breast cancer, and discuss the clinical translational
      challenge of identifying cancers that are reliant on a specific kinase for growth
      and survival. Substantial evidence suggests that subsets of breast cancer may be
      reliant on specific kinases, and that this could be exploited therapeutically.
      The heterogeneity of breast cancer, however, and the potential for adaptive
      switching between RTKs after inhibition of a single RTK, present challenges to
      targeting individual RTKs in the clinic SUMMARY: Targeting of RTKs in HER2
      negative breast cancer presents a major therapeutic opportunity in breast cancer,
      although robust selection strategies will be required to identify cancers with
      activation of specific RTKs if this potential is to be realized.

PMID- 24100347
TI  - Impact of 1 mmol dm(-3) concentrations of small molecules containing nitrogen
      based cationic groups on the oxygen reduction reaction on polycrystalline
      platinum in aqueous KOH (1 mol dm(-3)).
AB  - Alkaline anion-exchange membranes (AAEMs) containing cationic head-groups (e.g.
      involving quaternary ammonium and imidazolium groups) are of interest with regard
      to application in alkaline polymer electrolyte fuel cells (APEFCs). This initial
      ex situ study evaluated the effect of 1 mmol dm(-3) concentrations of model
      molecules containing (AAEM-relevant) cationic groups on the oxygen reduction
      reaction on a polycrystalline platinum disk (Ptpc) electrode in aqueous KOH (1
      mol dm(-3)). The cationic molecules studied were tetramethylammonium (TMA),
      benzyltrimethylammonium (BTMA), 1-benzyl-3-methylimidazolium (BMI), 1-benzyl-4
      aza-1-azoniabicyclo[2.2.2]octane (BAABCO) and 6-(benzyloxy)-N,N,N-trimethylhexan
      1-aminium (BOTMHA). Both cyclic and hydrodynamic linear sweep rotating disk
      electrode voltammetry techniques were used. The resulting voltammograms, derived
      estimates of apparent electrochemically active surface areas, Tafel slopes,
      apparent exchange-current densities and the number of electrons transferred (per
      O2 molecule) were compared. The results strongly suggest that 1 mmol dm(-3)
      concentrations of BTMA, BAABCO, and (especially) BMI seriously inhibit the
      catalytic activities of Ptpc in an aqueous KOH electrolyte at 25  degrees C. The
      negative influence of (benzene-ring-free) TMA and Cl(-) anions (KCl control
      experiment) appeared to be less severe. The separation of the trimethylammonium
      group from the benzene ring via a hexyloxy spacer chain (in BOTMHA) also produced
      a milder negative effect. 

PMID- 24100348
TI  - Visceral larva migrans presenting as multiple liver abscesses.
AB  - Eosinophilic necrotizing granulomas in the liver, known as visceral larva migrans
      (VLM), are a rare cause of liver abscesses. The term VLM refers to infections in
      human tissues caused by the larval stages of ascarid worms of dogs and cats. We
      report two cases of VLM which presented with high grade fever and abdominal pain
      for 3-4 months. Marked peripheral eosinophilia, multiple confluent perivenous
      lesions in the right lobe of liver with characteristic migratory tracts on
      imaging and biopsy evidence of necrotizing eosinophilic granulomas led to the
      diagnosis. Complete recovery was achieved with repeated courses of a combination
      of anthelmintics. 

PMID- 24100349
TI  - Childhood onset of stiff-man syndrome.
AB  - IMPORTANCE: Reports of pediatric-onset stiff-man syndrome (SMS) are rare. This
      may be an underrecognized disorder in child neurology practice. OBJECTIVE: To
      describe patients with disorders in the SMS spectrum beginning in childhood.
      DESIGN, SETTING, AND PARTICIPANTS: This study was a medical record review and
      serological evaluation conducted at child and adult neurology clinics at the Mayo
      Clinic, Rochester, Minnesota. Systematic review of the literature was conducted
      of patients who presented from 1984-2012 with onset of symptomatic SMS occurring
      at age 18 years or younger. MAIN OUTCOMES AND MEASURES: Response to symptomatic
      and immunotherapies, patient and physician reported, including modified Rankin
      scale. RESULTS: We identified 8 patients with childhood-onset SMS, representing
      5% of patients with SMS evaluated at Mayo Clinic during a period of 29 years (4
      were girls). The median age at symptom onset was 11 years (range, 1-14 years).
      The diagnosis in 3 patients was not established until adulthood (median symptom
      duration at diagnosis, 14 years; range, 0-46 years). The phenotypes encountered
      were: classic SMS (n = 5, involving the low back and lower extremities), variant
      SMS (n = 2, limited to 1 limb [with dystonic posture] or back), and progressive
      encephalomyelitis with rigidity and myoclonus (n = 1). Initial misdiagnoses
      included functional movement disorder (n = 2), generalized dystonia and
      parkinsonism (n = 1), and hereditary spastic paraparesis (n = 1). Six patients
      had 1 or more coexisting autoimmune disorders: type 1 diabetes mellitus (n = 4),
      thyroid disease (n = 2), and vitiligo (n = 2). Serologic study results revealed
      glutamic acid decarboxylase 65-IgG in all cases (median value, 754 nmol/L; range,
      0.06-3847 nmol/L; normal value, <= 0.02 nmol/L) and glycine receptor antibody in
      3 cases. Improvements were noted with symptomatic therapy (diazepam, 6 of 6
      patients treated, and oral baclofen, 3 of 3 treated) and immunotherapy
      (intravenous immune globulin, 3 of 4 treated and plasmapheresis, 3 of 4 treated).
      The 3 patients with glycine receptor antibody all improved with immunotherapy. At
      last follow-up, 4 patients had mild or no symptoms, but 4 had moderate or severe
      residual symptoms and required maintenance symptomatic therapy (n = 5) and
      immunotherapy (n = 4). Ten of 12 pediatric SMS cases identified by literature
      review had a severe whole-body phenotype resembling progressive encephalomyelitis
      with rigidity and myoclonus. CONCLUSIONS AND RELEVANCE: Childhood-onset SMS is a
      rare but underrecognized and treatable disorder. Serological and
      electrophysiological testing aid diagnosis.

PMID- 24100350
TI  - Control of the hematopoietic stem cell state.
AB  - Several studies have demonstrated the clonal transmission of distinct
      differentiation and self-renewal properties in hematopoietic stem cells during
      the regeneration of blood production in transplanted recipients. A recent
      publication now identifies Vwf expression as a discriminating marker of a
      hematopoietic stem cell state that is primed for platelet production in response
      to thrombopoietin, but also subject to developmental and other, as yet undefined,
      cues. 

PMID- 24100352
TI  - In situ polymerized superhydrophobic and superoleophilic nanofibrous membranes
      for gravity driven oil-water separation.
AB  - Creating an efficient, cost-effective method that can provide simple, practical
      and high-throughput separation of oil-water mixtures has proved extremely
      challenging. This work responds to these challenges by designing, fabricating and
      evaluating a novel fluorinated polybenzoxazine (F-PBZ) modified nanofibrous
      membrane optimized to achieve gravity driven oil-water separation. The membrane
      design is then realized by a facile combination of electrospun poly(m-phenylene
      isophthalamide) (PMIA) nanofibers and an in situ polymerized F-PBZ functional
      layer incorporating SiO2 nanoparticles (SiO2 NPs). By employing the F-PBZ/SiO2 NP
      modification, the pristine hydrophilic PMIA nanofibrous membranes are endowed
      with promising superhydrophobicity with a water contact angle of 161 degrees  and
      superoleophilicity with an oil contact angle of 0 degrees . This new membrane
      shows high thermal stability (350  degrees C) and good repellency to hot water
      (80  degrees C), and achieves an excellent mechanical strength of 40.8 MPa.
      Furthermore, the as-prepared membranes exhibited fast and efficient separation of
      oil-water mixtures by a solely gravity driven process, which makes them good
      candidates for industrial oil-polluted water treatments and oil spill cleanup,
      and also provided new insights into the design and development of functional
      nanofibrous membranes through F-PBZ modification. 

PMID- 24100351
TI  - Structural basis of PP2A activation by PTPA, an ATP-dependent activation
      chaperone.
AB  - Proper activation of protein phosphatase 2A (PP2A) catalytic subunit is central
      for the complex PP2A regulation and is crucial for broad aspects of cellular
      function. The crystal structure of PP2A bound to PP2A phosphatase activator
      (PTPA) and ATPgammaS reveals that PTPA makes broad contacts with the structural
      elements surrounding the PP2A active site and the adenine moiety of ATP. PTPA
      binding stabilizes the protein fold of apo-PP2A required for activation, and
      orients ATP phosphoryl groups to bind directly to the PP2A active site. This
      allows ATP to modulate the metal-binding preferences of the PP2A active site and
      utilize the PP2A active site for ATP hydrolysis. In vitro, ATP selectively and
      drastically enhances binding of endogenous catalytic metal ions, which requires
      ATP hydrolysis and is crucial for acquisition of pSer/Thr-specific phosphatase
      activity. Furthermore, both PP2A- and ATP-binding are required for PTPA function
      in cell proliferation and survival. Our results suggest novel mechanisms of PTPA
      in PP2A activation with structural economy and a unique ATP-binding pocket that
      could potentially serve as a specific therapeutic target. 

PMID- 24100353
TI  - Insight into highly selective photocatalytic oxidation of alcohols by a new
      trinuclear ruthenium complex with visible light.
AB  - A new ligand bearing two tpy moieties and one bpy unit (tpy = 2,2':6',2''
      terpyridine; bpy = 2,2'-bipyridine) linked by carbon-carbon single bonds and its
      corresponding trinuclear ruthenium complex were readily synthesized in high
      yield, and characterized by (1)H NMR spectroscopy, high-resolution electrospray
      ionization mass spectrometry (HR-ESI/MS) and elemental analysis. The ruthenium
      complex exhibited moderate catalytic activity towards selective oxidation of
      alcohols in water with visible light under an air atmosphere. Investigations of
      UV/vis spectra, electrochemistry and ESI/MS suggested that the catalytic cycle
      involves two processes, Ru(c)(II)-OH2/Ru(c)(III)-OH and Ru(c)(III)
      OH/Ru(c)(IV)=O. The effective electron transfer from the excited state
      *[Ru(tpy)2](2+) to [Co(NH3)5Cl]Cl2 is proposed to be responsible for the good
      activities of this visible-light-driven system under an air atmosphere.

PMID- 24100354
TI  - Evaluation of surveillance bias and the validity of the venous thromboembolism
      quality measure.
AB  - IMPORTANCE: Postoperative venous thromboembolism (VTE) rates are widely reported
      quality metrics soon to be used in pay-for-performance programs. Surveillance
      bias occurs when some clinicians use imaging studies to detect VTE more
      frequently than other clinicians. Because they look more, they find more VTE
      events, paradoxically worsening their hospital's VTE quality measure performance.
      A surveillance bias may influence VTE measurement if (1) greater hospital VTE
      prophylaxis adherence fails to result in lower measured VTE rates, (2) hospitals
      with characteristics suggestive of higher quality (eg, more accreditations) have
      greater VTE prophylaxis adherence rates but worse VTE event rates, and (3) higher
      hospital VTE imaging utilization use rates are associated with higher measured
      VTE event rates. OBJECTIVE: To examine whether a surveillance bias influences the
      validity of reported VTE rates. DESIGN, SETTING, AND PARTICIPANTS: 2010 Hospital
      Compare and American Hospital Association data from 2838 hospitals were merged.
      Next, 2009-2010 Medicare claims data for 954,926 surgical patient discharges from
      2786 hospitals who were undergoing 1 of 11 major operations were used to
      calculate VTE imaging (duplex ultrasonography, chest computed tomography/magnetic
      resonance imaging, and ventilation-perfusion scans) and VTE event rates. MAIN
      OUTCOMES AND MEASURES: The association between hospital VTE prophylaxis adherence
      and risk-adjusted VTE event rates was examined. The relationship between a
      summary score of hospital structural characteristics reflecting quality (hospital
      size, numbers of accreditations/quality initiatives) and performance on VTE
      prophylaxis and risk-adjusted VTE measures was examined. Hospital-level VTE event
      rates were compared across VTE diagnostic imaging rate quartiles and with a
      quantile regression. RESULTS: Greater hospital VTE prophylaxis adherence rates
      were weakly associated with worse risk-adjusted VTE event rates (r2 = 4.2%; P =
      .03). Hospitals with increasing structural quality scores had higher VTE
      prophylaxis adherence rates (93.3% vs 95.5%, lowest vs highest quality quartile;
      P < .001) but worse risk-adjusted VTE rates (4.8 vs 6.4 per 1000, lowest vs
      highest quality quartile; P < .001). Mean VTE diagnostic imaging rates ranged
      from 32 studies per 1000 in the lowest imaging use quartile to 167 per 1000 in
      the highest quartile (P < .001). Risk-adjusted VTE rates increased significantly
      with VTE imaging use rates in a stepwise fashion, from 5.0 per 1000 in the lowest
      quartile to 13.5 per 1000 in the highest quartile (P < .001). CONCLUSIONS AND
      RELEVANCE: Hospitals with higher quality scores had higher VTE prophylaxis rates
      but worse risk-adjusted VTE rates. Increased hospital VTE event rates were
      associated with increasing hospital VTE imaging use rates. Surveillance bias
      limits the usefulness of the VTE quality measure for hospitals working to improve
      quality and patients seeking to identify a high-quality hospital.

PMID- 24100359
TI  - Viral infection: interfering with HIV infection.

PMID- 24100357
TI  - Motor proteins and molecular motors: how to operate machines at the nanoscale.
AB  - Several classes of biological molecules that transform chemical energy into
      mechanical work are known as motor proteins or molecular motors. These nanometer
      sized machines operate in noisy stochastic isothermal environments, strongly
      supporting fundamental cellular processes such as the transfer of genetic
      information, transport, organization and functioning. In the past two decades
      motor proteins have become a subject of intense research efforts, aimed at
      uncovering the fundamental principles and mechanisms of molecular motor dynamics.
      In this review, we critically discuss recent progress in experimental and
      theoretical studies on motor proteins. Our focus is on analyzing fundamental
      concepts and ideas that have been utilized to explain the non-equilibrium nature
      and mechanisms of molecular motors. 

PMID- 24100360
TI  - On the front line: structural insights into plant-pathogen interactions.
AB  - Over the past decade, considerable advances have been made in understanding the
      molecular mechanisms that underpin the arms race between plant pathogens and
      their hosts. Alongside genomic, bioinformatic, proteomic, biochemical and cell
      biological analyses of plant-pathogen interactions, three-dimensional structural
      studies of virulence proteins deployed by pathogens to promote infection, in some
      cases complexed with their plant cell targets, have uncovered key insights into
      the functions of these molecules. Structural information on plant immune
      receptors, which regulate the response to pathogen attack, is also starting to
      emerge. Structural studies of bacterial plant pathogen-host systems have been
      leading the way, but studies of filamentous plant pathogens are gathering pace.
      In this Review, we summarize the key developments in the structural biology of
      plant pathogen-host interactions. 

PMID- 24100365
TI  - Literature-related discovery techniques applied to ocular disease: a vitreous
      restoration example.
AB  - PURPOSE OF REVIEW: Literature-related discovery and innovation (LRDI) is a text
      mining approach for bridging unconnected disciplines to hypothesize radical
      discovery. Application to medical problems involves identifying key disease
      symptoms, and identifying causes and treatments for those symptoms from
      throughout the biomedical literature. LRDI has not been applied to vitreoretinal
      ophthalmological problems previously. This review illustrates the use of LRDI for
      potential restoration of degenerated vitreous. RECENT FINDINGS: Vitreous
      restoration literature is very small; much research is aimed at vitreous
      composition and degradation, improving vitrectomy, and pharmacological
      vitreolysis. LRDI has the potential to find ways to slow, halt, or reverse the
      degradation through systemic improvement and myriad local treatments, some not
      ordinarily used by the ophthalmology community. SUMMARY: The many potential
      discoveries and innovations were generated within a larger context, namely that
      timely healing required cause removal, healing obstacle removal, and healing
      acceleration (focused treatments) in an integrated manner. Although many
      potential causes, healing obstacles, and healing accelerations were identified
      strictly from the premier published literature, causes and obstacles that may
      have been operable but were not found in the literature were also postulated, as
      were gaps in the research that covered these potential causes and obstacles and
      unresearched treatments as well.

PMID- 24100361
TI  - Geminiviruses: masters at redirecting and reprogramming plant processes.
AB  - The family Geminiviridae is one of the largest and most important families of
      plant viruses. The small, single-stranded DNA genomes of geminiviruses encode 5-7
      proteins that redirect host machineries and processes to establish a productive
      infection. These interactions reprogramme plant cell cycle and transcriptional
      controls, inhibit cell death pathways, interfere with cell signalling and protein
      turnover, and suppress defence pathways. This Review describes our current
      knowledge of how geminiviruses interact with their plant hosts and the functional
      consequences of these interactions. 

PMID- 24100364
TI  - Ocular manifestations of drug and alcohol abuse.
AB  - PURPOSE OF REVIEW: The purpose of this study is to review commonly encountered
      adverse ocular effects of illicit drug use. RECENT FINDINGS: Drug and alcohol
      abuse can produce a variety of ocular and neuro-ophthalmic side effects. Novel,
      so-called 'designer', drugs of abuse can lead to unusual ocular disorders. Legal
      substances, when used in manners for which they have not been prescribed, can
      also have devastating ophthalmic consequences. SUMMARY: In this review, we will
      systematically evaluate each part of the visual pathways and discuss how
      individual drugs may affect them.

PMID- 24100366
TI  - Autoimmune retinopathy.
AB  - PURPOSE OF REVIEW: Autoimmune retinopathy (AIR) is an immune-mediated disorder
      characterized by progressive visual loss, abnormal electroretinographic and
      visual field findings in the presence of circulating anti-retinal antibodies.
      This review highlights advances made toward understanding the pathophysiology,
      clinical manifestations, and trends in the management of AIR. RECENT FINDINGS:
      The pathophysiology of AIR is likely antibody-mediated. AIR serum autoantibodies
      are variable in their size and retinal tissue they target and can also be present
      in healthy controls and multiple autoimmune diseases. Rarely, AIR may be
      associated with dysregulated self-tolerance mechanisms in the thymus. Despite
      progress in research, our understanding of AIR remains incomplete. Lack of
      standardized methods for anti-retinal antibody testing continues to challenge the
      interpretation of seropositivity. Conventional immunosuppressives have been
      further studied, and promising immunomodulatory therapies, such as targeted B
      cell therapy, have been introduced. Newer imaging modalities such as fundus
      autofluorescence and spectral domain optical coherence tomography may be helpful
      in diagnosis, monitoring progression of disease and response to treatment.
      SUMMARY: AIR is a rare but vision-threatening disease whose pathogenesis is
      poorly defined. Lack of standardized clinical or laboratory criteria further
      complicates the diagnosis and management. Despite recent progress, further basic
      science research into the autoimmune process is needed. Prospective controlled
      clinical trials with immunomodulatory therapy can help define future treatment
      paradigms.

PMID- 24100367
TI  - Neuro-ophthalmologic side-effects of systemic medications.
AB  - PURPOSE OF REVIEW: Systemic medications may cause side-effects manifesting
      primarily as neuro-ophthalmologic problems. It is paramount for the physician to
      be updated on both well recognized and novel associations between drugs and their
      potential adverse reactions. RECENT FINDINGS: There is a growing list of
      medications that can cause pupil dilation, pupil constriction, dyschromatopsia,
      worsening of ocular myasthenia gravis, posterior reversible leukoencephalopathy
      syndrome, pseudotumor cerebri, disturbances in eye movements, accommodation
      problems, or optic neuropathy. This is partly due to the increasing number of
      drugs available in each class, but also to the increased recognition of neuro
      ophthalmological disorders. SUMMARY: This review discusses neuro-ophthalmological
      problems and the medications that may precipitate them.

PMID- 24100368
TI  - The contribution of optical coherence tomography in neurodegenerative diseases.
AB  - PURPOSE OF REVIEW: This review investigates the contribution of optical coherence
      tomography (OCT) to monitoring of neurodegeneration in the anterior visual
      pathway of patients with neuromyelitis optica, Alzheimer's disease, and
      Parkinson's disease. Despite a 'normal' regular ophthalmologic examination, some
      patients present visual complaints, and OCT might better explain the mechanism
      associated to neuronal and axonal losses that contribute to this clinical
      condition. RECENT FINDINGS: The eye can be considered a 'window' to the central
      nervous system that can be directly accessed through OCT. Prior studies have
      suggested that pathologic processes in the brain are very similar to what happens
      in the eye in neurodegenerative diseases, and OCT has confirmed these
      abnormalities regarding the anterior visual pathway. It is supposed that
      transsynaptic neurodegeneration in lesions of the posterior visual pathway may
      play a role in the neurodegeneration process of the anterior visual pathway.
      SUMMARY: Retinal nerve fiber layer, retinal ganglion cells, and inner retinal
      layers are considered surrogate biomarkers in the progression of
      neurodegenerative diseases. Because OCT is able to accurately measure
      neuropathological ocular features, its application has increased both in
      neuroprotection studies and in treatment. In fact, it may prove to be a unique
      evaluation tool in comparison with conventional visual tests. VIDEO ABSTRACT:
      (Supplementary Digital content 1, http://links.lww.com/COOP/A10).

PMID- 24100369
TI  - A diagnostic challenge: dilated pupil.
AB  - PURPOSE OF REVIEW: Dilated pupil is a diagnostic challenge encountered by
      neurologists and ophthalmologists. The aim of this review is to provide an
      overview of the current data and guidelines concerning dilated pupils. RECENT
      FINDINGS: The majority of recent reports on dilated pupils are indicative of
      several medical conditions that require evaluation. The topical synthetic
      parasympatholytic agents; local contamination of antihistamines with their
      antimuscarinic effects; atropine, scopolamine, and tropane alkaloids in all
      species of Datura plants may produce mydriasis. SUMMARY: The causes of pupillary
      dilatation can be unilateral, bilateral, and transient. The clinical approach to
      dilated pupils requires stepwise evaluation, and based on the findings,
      unnecessary and costly procedures can be avoided.

PMID- 24100370
TI  - Toxic optic neuropathies.
AB  - PURPOSE OF REVIEW: Many causes of toxic optic neuropathy have been described to
      date and novel causes of toxicity are continuously being added to the current
      literature. The pathophysiological basis for the toxicity or a direct causal
      relationship is yet to be determined for many of these agents. This review
      highlights the reports made over the last year about the commonly reported
      agents, with emphasis on the mechanisms of toxicity. RECENT FINDINGS:
      Mitochondria of retinal ganglion cells and papillomacular bundle in particular
      could be the common target of many causes of toxic optic neuropathy, if not all.
      Agents or their metabolites responsible for the toxicity seem to interfere with
      the oxidative phosphorylation in mitochondria, causing a buildup of reactive
      oxidation species, energy depletion, oxidative stress, and activation of
      apoptosis. SUMMARY: Further data are still necessary to understand how some of
      the usual suspects cause damage to the optic nerve or whether they indeed cause
      damage or not. A basic algorithm, as proposed, could be a useful addition to
      discriminate the novel causes of toxic optic neuropathy. VIDEO ABSTRACT: See the
      Supplemental Digital Content 1 (http://links.lww.com/COOP/A11).

PMID- 24100371
TI  - Drug-induced uveitis.
AB  - PURPOSE OF REVIEW: Although more than 50% of all uveitis cases have no
      identifiable cause, certain medications can cause ocular inflammation and are
      often overlooked. Drug-induced ocular inflammation has increased in frequency
      with the advent of new bisphosphonates, antitumor necrosis factor biologic
      agents, and intravitreal triamcinolone and antivascular endothelial growth factor
      medications. Identification of these inciting drugs will simplify work-up and
      management of patients with uveitis and improve visual outcomes. RECENT FINDINGS:
      This review briefly focuses on the drugs that have long been known to be strongly
      associated with uveitis and emphasize new observations about these associations.
      It will also highlight the newest medications associated with uveitis and
      scleritis. The strength of the association between each drug and uveitis will be
      quantified and categorized into definite, probable, possible, and unlikely causes
      of uveitis utilizing Naranjo's classification criteria. SUMMARY: Drug-induced
      uveitis has become increasingly recognized in association with a number of
      commonly used systemic, intraocular, and topical medications. A detailed history
      is often all that is needed to identify these important, often overlooked, and
      readily curable causes of uveitis. Most cases of drug-induced uveitis respond
      promptly to discontinuation of the suspected agent in conjunction with topical
      corticosteroid and cycloplegic therapy.

PMID- 24100372
TI  - Retinoblastoma.
AB  - PURPOSE OF REVIEW: Retinoblastoma is the most common malignant intraocular tumor
      of childhood. Treatment and diagnostic modalities associated to this condition
      are changing rapidly as our understanding of this condition crystallizes. The
      purpose of this review is to provide an update of the current understanding of
      retinoblastoma. RECENT FINDINGS: Knowledge on tumorigenesis and genomic
      expression has expanded tremendously with the development of a mouse model for
      retinoblastoma. Tumor hypoxia has been identified as a significant step in the
      tumor progression and a novel target for future treatments. Current globe-sparing
      therapies, including periocular carboplatin, selective ophthalmic artery
      chemoreduction, intravitreal melphalan, and focal consolidation are being used
      and investigated actively. Diagnosis and the management of retinoblastoma is also
      undergoing major advances including wide-field photography, autofluorescence, and
      high-resolution optical coherence tomography. SUMMARY: Progressive advances in
      the understanding of retinoblastoma pathogenesis continue to lead treatment
      strategies. Improvements in the diagnosis and management of retinoblastoma are
      improving morbidity and mortality associated to this condition in the developed
      nations. However, it is of outmost importance to flatten the international
      boundaries to offer prompt care to retinoblastoma children in underdeveloped
      communities.

PMID- 24100373
TI  - Differentiating retinal from optic nerve syndromes.
AB  - PURPOSE OF REVIEW: Differentiate between optic nerve and retinal disease that
      share common characteristics utilizing clinical history, examination, and
      ancillary testing. RECENT FINDINGS: Autofluorescence is a quick and noninvasive
      test that is helpful in detecting macular edema and deposition of lipofuscin.
      Optical coherence tomography (OCT) is becoming an indispensable tool in detecting
      subtle macular abnormalities that can be missed on funduscopic examination.
      Multifocal electroretinogram can also help in early screening of focal macular
      dystrophy. SUMMARY: Many patients present to the ophthalmology clinic with
      decreased vision, and occasionally it can be difficult to find a clear cause to
      the vision loss. Such situations, not infrequently, require the ophthalmologist
      to differentiate between optic nerve and retinal diseases that can share some
      common characteristics. The ability to use the clinical history and examination
      along with additional ancillary testing including OCT, electrophysiology, and
      fluorescein angiography to differentiate optic nerve from retinal disease can be
      very helpful in formulating a differential and ultimately establishing a
      diagnosis.

PMID- 24100374
TI  - Clinical utility and assessment of cyclodeviation.
AB  - PURPOSE OF REVIEW: This article reviews and updates basic concepts, diagnosis and
      treatment of cyclotorsion. RECENT FINDINGS: Cyclodeviation in congenital superior
      oblique palsy (SOP) seems to correlate with the extent of superior oblique muscle
      hypoplasia. Genetic polymorphisms such as PHOX2B polymorphism, considered to be
      risk factors for congenital fibrosis of the extraocular muscles, may play a role
      in SOP and consequently in cyclotorsion. Two components of the ocular tilt
      reaction, ocular torsion and tilt of subjective visual vertical, seem to share
      similar sites of impairment in the brainstem. Harada-Ito surgery continues to be
      the procedure of choice in patients with isolated cyclodeviation, evidencing
      better outcome if less than 10 degrees  of preoperative excyclotorsion and
      preoperative fusion exist. Ocular torsion is not infrequent in patients with
      intermittent exotropia, especially in the most exo-deviated eye, emphasizing a
      possible role in pathogenesis. A new device for the assessment of dynamic torsion
      during ocular counter roll response using after-image has been described.
      Similarly, a new method to measure objective ocular torsion using retinal arcade
      tilt as a reference has been proposed. Finally, torsional data transformation
      such as the sum of angles of excyclodeviation, rather than using the angle of
      excyclodeviation of the paretic eye, is becoming increasingly popular among
      studies on torsion. SUMMARY: Exciting developments on ocular torsion have been
      described recently, and new ways to access and interpret ocular torsion have been
      devised as well.

PMID- 24100375
TI  - Suppression of the death gene BIK is a critical factor for resistance to
      tamoxifen in MCF-7 breast cancer cells.
AB  - Apoptosis is controlled by the BCL-2 family of proteins, which can be divided
      into three different subclasses based on the conservation of BCL-2 homology
      domains. BIK is a founding member of the BH3-only pro-apoptotic protein family.
      BIK is predominantly localized in the endoplasmic reticulum (ER) and induces
      apoptosis through the mitochondrial pathway by mobilizing calcium from the ER to
      the mitochondria. In this study, we determined that suppression of the death gene
      Bik promotes resistance to tamoxifen (TAM) in MCF-7 breast cancer cells. We
      utilized small interfering (siRNA) to specifically knockdown BIK in MCF-7 cells
      and studied their response to tamoxifen. The levels of cell apoptosis, the
      potential mitochondrial membrane (?Psi(m)), and the activation of total caspases
      were analyzed. Western blot analysis was used to determine the expression of some
      BCL-2 family proteins. Flow cytometry studies revealed an increase in apoptosis
      level in MCF-7 cells and a 2-fold increase in relative BIK messenger RNA (mRNA)
      expression at a concentration of 6.0 MUM of TAM. BIK silencing, with a specific
      RNAi, blocked TAM-induced apoptosis in 45 +/- 6.78% of cells. Moreover, it
      decreased mitochondrial membrane potential (Psim) and total caspase activity, and
      exhibited low expression of pro-apoptotic proteins BAX, BAK, PUMA and a high
      expression of BCl-2 and MCL-1. The above suggests resistance to TAM, regulating
      the intrinsic pathway and indicate that BIK comprises an important factor in the
      process of apoptosis, which may exert an influence the ER pathway, which
      regulates mitochondrial integrity. Collectively, our results show that BIK is a
      central component of the programmed cell death of TAM-induced MCF-7 breast cancer
      cells. The silencing of BIK gene will be useful for future studies to establish
      the mechanisms of regulation of resistance to TAM.

PMID- 24100377
TI  - Experimental and theoretical study of the distance dependence of metal-enhanced
      fluorescence, phosphorescence and delayed fluorescence in a single system.
AB  - Distance dependent singlet and triplet metal-enhanced emission of eosin from
      silica coated silver island films (SiFs) has been studied by steady-state and
      time resolved fluorescence techniques, along with theoretical finite difference
      time domain (FDTD) numerical simulations, to understand how the thickness of the
      dielectric coating surrounding silver nanoparticles fundamentally affects
      luminescence enhancement. Our findings suggest that the distance dependence of
      metal-enhanced phenomena such as fluorescence, phosphorescence and delayed
      fluorescence is underpinned by the decay of the electric near-field, and
      depending on the actual silver silica sample embodiment, one can see either
      decreased or enhanced luminescence. These results not only expand our current MEF
      thinking but also suggest that one may well be able to approximate plasmon
      enhanced luminescence values. 

PMID- 24100376
TI  - VSL#3 probiotic modifies mucosal microbial composition but does not reduce
      colitis-associated colorectal cancer.
AB  - Although probiotics have shown success in preventing the development of
      experimental colitis-associated colorectal cancer (CRC), beneficial effects of
      interventional treatment are relatively unknown. Here we show that interventional
      treatment with VSL#3 probiotic alters the luminal and mucosally-adherent
      microbiota, but does not protect against inflammation or tumorigenesis in the
      azoxymethane (AOM)/Il10-/- mouse model of colitis-associated CRC. VSL#3 (109
      CFU/animal/day) significantly enhanced tumor penetrance, multiplicity, histologic
      dysplasia scores, and adenocarcinoma invasion relative to VSL#3-untreated mice.
      Illumina 16S sequencing demonstrated that VSL#3 significantly decreased (16-fold)
      the abundance of a bacterial taxon assigned to genus Clostridium in the mucosally
      adherent microbiota. Mediation analysis by linear models suggested that this
      taxon was a contributing factor to increased tumorigenesis in VSL#3-fed mice. We
      conclude that VSL#3 interventional therapy can alter microbial community
      composition and enhance tumorigenesis in the AOM/Il10-/- model.

PMID- 24100378
TI  - Protein-bound polysaccharide-K augments the anticancer effect of fluoropyrimidine
      derivatives possibly by lowering dihydropyrimidine dehydrogenase expression in
      gastrointestinal cancers.
AB  - Protein-bound polysaccharide-K (PSK) enhances the antitumor effect of anticancer
      drug when used clinically in combination with such drugs. PSK is known to act by
      immune-mediated mechanisms; however, the relationship between PSK and metabolic
      enzymes of anticancer drugs is unknown. We used the collagen gel droplet-embedded
      culture drug sensitivity test (CD-DST) clinically to evaluate the sensitivity of
      anticancer drugs. In the present study, we modified the CD-DST by adding
      peripheral blood mononuclear cells (PBMCs) (immuno-CD-DST) and examined the
      antitumor effect of PSK in combination with anticancer drugs. First, HCT116 human
      colon cancer cells were cultured with PSK and 5-fluorouracil (5-FU) or 5'-deoxy-5
      fluorouridine (5'-DFUR) in the presence or absence of PBMCs, and the
      antiproliferative effects were compared. In the presence of PBMCs, PSK augmented
      the inhibitory effects of 5-FU and 5'-DFUR on HCT116 cell proliferation. Next,
      using human gastric cancer and colon cancer cell lines, the effects of PSK on
      mRNA expression of various metabolic enzymes of fluoropyrimidines:
      dihydropyrimidine dehydrogenase (DPD), thymidylate synthase, thymidine
      phosphorylase and orotate phosphoribosyl transferase, were examined by real-time
      PCR. PSK significantly enhanced DPD mRNA expression in all of the cancer cell
      lines tested, but not those of the other enzymes. Addition of IFN-alpha and
      TRAIL, cytokines known to inhibit DPD expression, to the cultures reduced DPD
      mRNA expression in the cancer cells. When PBMC samples collected from healthy
      volunteers were cultured with PSK, IFN-alpha mRNA expression increased in 3 of
      the 5 PBMC samples, while TRAIL mRNA expression was unchanged. The present
      results propose the possibility that PSK induces PBMCs to express IFN-alpha which
      inhibits DPD expression, and consequently augments the antitumor effect of 5-FU
      or 5'-DFUR. Immuno-CD-DST is useful for evaluating drugs with immunological
      mechanisms of action. 

PMID- 24100379
TI  - Recent progress and remaining challenges in sulfur-based lithium secondary
      batteries--a review.
AB  - This review is an attempt to report the latest development in lithium-sulfur
      batteries, namely the storage system that, due to its potential energy content,
      is presently attracting considerable attention both for automotive and stationary
      storage applications. We show here that consistent progress has been achieved, to
      the point that this battery is now considered to be near to industrial
      production. However, the performance of present lithium-sulfur batteries is still
      far from meeting their real energy density potentiality. Thus, the considerable
      breakthroughs so far achieved are outlined in this review as the basis for
      additional R&D, with related important results, which are expected to occur in
      the next few years. 

PMID- 24100380
TI  - Does the width of the surgical margin of safety or premalignant dermatoses at the
      negative surgical margin affect outcome in surgically treated penile cancer?
AB  - AIMS: To evaluate the prognostic impact of the width of negative surgical margins
      (NSM) and associated and preinvasive lesions at the NSM in patients with penile
      squamous cell cancer (PSC). METHODS: Enrolling 87 patients with NSM who underwent
      surgery for PSC, the archived margin slides and entirely wax-embedded surgical
      margins were retrieved from the pathology files. After step sections were cut,
      margins were stained with antibodies against CK5/6, p16, p53 and Ki-67 and
      subjected to in situ hybridisation for high-risk human papillomavirus (HPV). All
      NSM were histologically examined for squamous hyperplasia (SH), lichen sclerosus
      (LS) and subtypes of penile intraepithelial neoplasia (PeIN). Then, histological
      findings were correlated with cancer-specific mortality (CSM, median follow-up 34
      months; IQR 6-70). RESULTS: All NSM were negative for high-risk HPV and exhibited
      SH (p16 and p53 negative, Ki-67 variably positive), LS (p16 negative, variable
      p53 and Ki-67 positivity) and differentiated PeIN (dPeIN; p16 negative, Ki-67
      positive, variable p53 positivity) in 28 (32%), 30 (34%) and 22 (25%) cases,
      respectively, whereas PeIN subtypes other then dPeIN did not occur. Pathological
      tumour stage was the only independent predictive parameter with respect to CSM in
      the multivariable analysis (p=0.001). CONCLUSIONS: SH, LS and dPeIN are frequent
      histological findings at the NSM of surgically treated PSC. However, neither the
      width of the NSM nor dPeIN, LS or SH at the NSM influences prognostic outcome.

PMID- 24100381
TI  - The BH3 mimetic S1 induces endoplasmic reticulum stress-associated apoptosis in
      cisplatin-resistant human ovarian cancer cells although it activates autophagy.
AB  - SKOV3/DDP human ovarian cancer cells have been shown to be resistant to
      cisplatin. Although the BH3 mimetic S1 induces cell death in several types of
      tumor cells, it is unclear whether it induces death in drug-resistant cells.
      Herein, we found that S1 induced endoplasmic reticulum (ER) stress-associated
      apoptosis in both SKOV3 and SKOV3/DDP cells. S1 activated autophagy at early time
      points in SKOV3/DDP cells, and inhibition of autophagy increased ER stress
      associated apoptosis. Collectively, our data indicate that autophagy plays a
      protective role, but it cannot protect against S1-induced cell death in cisplatin
      resistant SKOV3/DDP cells. 

PMID- 24100382
TI  - Chiral and achiral imidazole-linked tetrahedral zinc phosphonate frameworks with
      photoluminescent properties.
AB  - Presented here are three imidazole-linked tetrahedral zinc phosphonate frameworks
      based on a special ligand 2-(1-imidazole)-1-hydroxyl-1,1'-ethylidenediphosphonic
      acid (= ImhedpH4) with both an organic imidazole linker and inorganic phosphonate
      groups. Three new compounds, namely, [Zn2(ImhedpH2)2(ox)](H2ppz) (1),
      Zn3(ImhedpH)2(H2O)4 (2) and [Zn3(Imhedp)2](H2ppz) (3) (ox = oxalate and ppz =
      piperazine), were obtained by hydrothermal synthesis and structurally
      characterized by single-crystal X-ray diffraction. Compound 1 shows a chain
      structure with the ox ligands linking the [Zn2(ImhedpH2)2] units, and the
      resulting chains are further connected to form a 3D structure through the strong
      N-H...O and O-H...O hydrogen bonds between the neighboring chains. Compound 2
      displays an inorganic layer structure with dangling imidazole units, where these
      protonated imidazoles also act as pillars between adjacent inorganic layers.
      Compound 3 features an unusual chiral three-dimensional (3D) Zn-Imhedp framework
      with guest H2ppz(2+) cations. It can be topologically represented as a 4
      connected qtz network. Furthermore, the luminescent properties of the three
      compounds were investigated in the solid state.

PMID- 24100383
TI  - Acute intake of radionuclides immediately after the incident as the main
      contributor of the internal radiation exposure after Fukushima Daiichi nuclear
      disaster.

PMID- 24100384
TI  - Progranulin does not inhibit TNF and lymphotoxin-alpha signalling through TNF
      receptor 1.
AB  - Progranulin (proepithelin, granulin precursor) has been recently suggested to
      exhibit anti-inflammatory properties by directly binding to tumour necrosis
      factor (TNF) receptors and thereby inhibiting TNF signalling by Tang et al. This
      finding was challenged by Chen et al. and no interaction between progranulin and
      TNF receptor (TNFR) 1 or 2 was observed. We tested the ability of recombinant
      progranulin from different commercial sources to inhibit TNF- or lymphotoxin
      alpha-induced signalling through TNFR1. We observed that progranulin does not
      affect signalling and cell death induction downstream of TNF or lymphotoxin
      alpha. Our results suggest that the anti-inflammatory role of progranulin is not
      mediated through direct inhibition of TNFR1. 

PMID- 24100385
TI  - Gut TFH and IgA: key players for regulation of bacterial communities and immune
      homeostasis.
AB  - The main function of the immune system is to protect the host against pathogens.
      However, unlike the systemic immune system, the gut immune system does not
      eliminate, but instead nourishes complex bacterial communities and establishes
      advanced symbiotic relationships. Immunoglobulin A (IgA) is the most abundant
      antibody isotype in mammals, produced mainly in the gut. The primary function of
      IgA is to maintain homeostasis at mucosal surfaces, and studies in mice have
      demonstrated that IgA diversification has an essential role in the regulation of
      gut microbiota. Dynamic diversification and constant adaptation of IgA responses
      to local microbiota require expression of activation-induced cytidine deaminase
      by B cells and control from T follicular helper and Foxp3(+) T cells in germinal
      centers (GCs). We discuss the finely tuned regulatory mechanisms for IgA
      synthesis in GCs of Peyer's patches and emphasize the roles of CD4(+) T cells for
      IgA selection and the maintenance of appropriate gut microbial communities
      required for immune homeostasis. 

PMID- 24100386
TI  - The interplay between pathogen-associated and danger-associated molecular
      patterns: an inflammatory code in cancer?
AB  - There is increasing evidence of a close link between inflammation and cancer, and
      at the core of inflammation there are both pathogen-associated molecular patterns
      (PAMPs) and danger (or damage)-associated molecular patterns (DAMPs).
      Microorganisms harbor molecules structurally conserved within groups called PAMPs
      that are recognized by specific receptors present on immune cells, such as
      monocytes and dendritic cells (DCs); these are the pattern recognition receptors
      (PRRs). Activation through different PRRs leads to production of pro-inflammatory
      cytokines. A robust immune response also requires the presence of endogenous
      molecules that pose 'danger' to self-tissues and are produced by damaged or
      stressed cells; these are the DAMPs, which act also as inducers of inflammation.
      PAMPs and DAMPs are each recognized by a limited set of receptors that in number
      probably do not exceed 100. PAMPs and DAMPs interact with each other, and a
      single PRR can bind to a PAMP as well as a DAMP. Within this framework, we
      propose that PAMPs and DAMPs act in synchrony, modifying the activation threshold
      of one another. Thus, the range of PAMP-DAMP partnerships defines the course of
      inflammation, in a predictable manner, in an 'inflammatory code'. The definition
      of relevant PAMP-DAMP complexes is important for the understanding of
      inflammatory disorders in general, and of cancer in particular. Here, we review
      relevant findings that support the notion of a PAMP-DAMP-based inflammatory code,
      with emphasis on cancer immunology and immunotherapy. 

PMID- 24100387
TI  - Retargeting NK-92 for anti-melanoma activity by a TCR-like single-domain
      antibody.
AB  - The efficacy of immunotherapy based on natural killer (NK) cells is hampered by
      intrinsic non-specific cytotoxicity and insufficient activation of NK cells.
      Here, we confer the T-cell receptor-like (TCR-like) specificity on NK cells,
      taking advantage of both the innate and adaptive immune arms of the immune
      response to generate enhanced anti-melanoma activity. The TCR-like antibody (Ab)
      GPA7 was selected against melanoma-associated gp100/human leukocyte antigen (HLA)
      A2 complex and then fused to intracellular domain of CD3-zeta chain. This fusion
      construct was incorporated into NK-92MI cell line and expressed as a chimeric
      antigen receptor on the surface of the cell. The anti-tumour activity of the
      transgenic NK-92MI-GPA7-zeta cell line was assessed against melanoma in vitro and
      in vivo. The engineered NK-92MI-GPA7-zeta cells could recognize melanoma cells in
      the context of HLA-A2 and showed enhanced killing of both melanoma cell lines and
      primary melanoma. Furthermore, adoptively transferred NK-92MI-GPA7-zeta cells
      significantly suppressed the growth of human melanoma in a xenograft model in
      mice. Collectively, these results demonstrate that the TCR-like Ab, GPA7, could
      redirect NK cells to target the intracellular antigen gp100 and enhance anti
      melanoma activity, providing a promising immunotherapeutic strategy to prevent
      and treat melanoma. 

PMID- 24100388
TI  - Immunology and Cell Biology Publication of the Year Awards 2012.

PMID- 24100389
TI  - The role of acetylation in TLR4-mediated innate immune responses.
AB  - Toll-like receptor 4 (TLR4) plays a critical role in the innate immune response
      to Gram-negative bacterial infection. A large number of the components involved
      in TLR4 signaling pathways have been identified over the past ten years. Recent
      studies focusing on the post-translational modification of TLR4 signaling
      pathways have begun expanding our knowledge of the impact of lysine acetylation
      on TLR4 signaling cascades. In this review, we will focus on the potential roles
      of acetylation in TLR4-mediated innate immune responses. 

PMID- 24100390
TI  - Redox balance of mouse medullary CD4 single-positive thymocytes.
AB  - After positive selection, the newly differentiated single-positive (SP)
      thymocytes undergo negative selection to eliminate autoreactive T cells,
      functional maturation to acquire immunocompetence and egress capability. To
      investigate whether the intracellular reduction/oxidation (redox) balance has an
      important role on SP maturation, the levels of intracellular reactive oxygen
      species (ROS) and the expression of proteins that regulate ROS were compared
      among the four subsets of mouse TCRalphabeta(+)CD4(+)CD8(-) thymocytes (SP1-SP4)
      that represent sequential stages of SP differentiation program. A gradual
      increase of ROS and a gradual decrease of thioredoxin were revealed along the SP
      maturation process. The high ROS level at the mature SP stage did not result from
      a specific enrichment at this stage of natural regulatory T cells and SP
      thymocytes undergoing negative selection (Helios positive). An increase of ROS in
      the most mature SP4 cells resulted in enhanced cytokine production upon
      stimulation, whereas an early increase of ROS in the immature SP1 thymocytes
      resulted in enhanced apoptosis. Aire(-/-) mice that have defects in negative
      selection and a developmental blockage at the SP3-SP4 transition showed
      significantly less ROS in SP3 thymocytes. Thymic epithelial cells that have been
      shown to promote SP maturation in vitro also increased the ROS level of SP
      thymocytes. These results suggest that ROS may be involved in promoting the
      functional maturation of CD4(+) SPs and thymic medullary microenvironment
      contributes to the pro-oxidant shift of SP thymocytes. 

PMID- 24100394
TI  - A child with bullous skin lesions. Linear IgA dermatosis.

PMID- 24100395
TI  - Distracted driving and motor vehicle crashes among teens.

PMID- 24100396
TI  - Proteinuria: does vitamin D treatment improve outcomes in CKD?
AB  - In a meta-analysis of randomized trials, de Borst and colleagues report that
      vitamin D therapy reduces proteinuria and might also slow the progression of
      chronic kidney disease. In light of the limited options for renoprotective
      therapy, we evaluate whether this evidence for vitamin D treatment justifies a
      large, definitive trial.

PMID- 24100397
TI  - Transplantation: increased recipient BMI is associated with adverse outcomes
      after kidney transplantation.

PMID- 24100398
TI  - Transplantation: Donor-derived skin cancer in a kidney transplant recipient.
AB  - Skin carcinomas, triggered by ultraviolet light, commonly develop post
      transplantation and are associated with substantial morbidity and mortality. A
      recent study in kidney transplant recipients has shown that some of these tumours
      arise from donor-derived cells. This phenomenon is interesting for the study of
      carcinogenesis, although its effect on clinical practice is unknown.

PMID- 24100400
TI  - Glomerular disease: MN linked to improved prognosis in anti-GBM disease.

PMID- 24100399
TI  - Evaluating bone quality in patients with chronic kidney disease.
AB  - Bone of normal quality and quantity can successfully endure physiologically
      imposed mechanical loads. Chronic kidney disease-mineral and bone disorder (CKD
      MBD) adversely affects bone quality through alterations in bone turnover and
      mineralization, whereas bone quantity is affected through changes in bone volume.
      Changes in bone quality can be associated with altered bone material, structure,
      or microdamage, which can result in an elevated rate of fracture in patients with
      CKD-MBD. Fractures cannot always be explained by reduced bone quantity and,
      therefore, bone quality should be assessed with a variety of techniques from the
      macro-organ level to the nanoscale level. In this Review, we demonstrate the
      importance of evaluating bone from multiple perspectives and hierarchical levels
      to understand CKD-MBD-related abnormalities in bone quality. Understanding the
      relationships between variations in material, structure, microdamage, and
      mechanical properties of bone in patients with CKD-MBD should aid in the
      development of new modalities to prevent, or treat, these abnormalities. 

PMID- 24100401
TI  - Therapy for patients with CKD and low bone mineral density.
AB  - Patients with chronic kidney disease (CKD) have a high risk of bone fracture
      owing to their low bone mineral density, which resembles that of postmenopausal
      osteoporosis. However, the mineral and bone disorder associated with CKD (CKD
      MBD) is more complex than osteoporosis and the same treatments might not be
      appropriate. In particular, vascular calcifications are strongly associated with
      CKD-MBD, and must be taken into consideration. Post hoc analyses of data from
      pivotal osteoporosis studies suggest that in patients with mild stage 3 CKD and
      normal parathyroid hormone (PTH), calcium and phosphate measurements,
      conventional medications for osteoporosis (such as raloxifene, bisphosphonates,
      teriparatide and denosumab) are effective at reducing fracture rates. However,
      for patients with stage 4-5 CKD, or those with abnormal PTH and mineral values,
      the available data are insufficient to determine whether these commonly used
      medications are effective against fractures. Moreover, all medications used to
      treat osteoporosis have known or potential adverse effects in patients with CKD.
      Medicines that increase bone formation by upregulating Wnt signalling have shown
      promise in patients with osteoporosis and might be used to treat CKD-MBD in the
      future, but off-target effects could limit their use in in this setting. 

PMID- 24100402
TI  - Risk factors: predicting prognosis in patients with rhabdomyolysis.
AB  - A recent study developed a formula predicting hard outcomes of rhabdomyolysis
      (dialysis and death). Based on a rigid analytical approach, an eight factor score
      was elaborated with acceptable prognostic value, but clinical usefulness at this
      time seems limited. Perhaps the most promising application is for triage.

PMID- 24100404
TI  - Overactive bladder in diabetes mellitus patients: a questionnaire-based
      observational investigation.
AB  - PURPOSE: Bladder dysfunction, secondary to diabetes, is mainly characterized by
      poor bladder emptying and overflow incontinence. However, there is evidence in
      literature that storage symptoms, as those suggestive for overactive bladder
      (OAB), may also affect people with diabetes. The aim of this study was to
      evaluate the prevalence of overactive bladder, the complaint of urinary urgency
      with/without urge incontinence, usually with frequency and nocturia, in people
      with diabetes compared to healthy subjects (control group). METHODS: Symptoms
      were assessed through the overactive bladder questionnaire (OAB-q), an
      investigative tool, specifically developed for OAB diagnosis. RESULTS: OAB-q
      scores resulted higher in diabetic people than those of the control group. Age
      and disease duration resulted in measurements that showed a statistical
      correlation with the OAB-q scores. CONCLUSIONS: OAB symptoms are more prevalent
      in diabetic people than in non-diabetic people. This prompts further research to
      determine whether the onset of OAB symptoms can be considered as an indicator of
      diabetic neuropathy.

PMID- 24100405
TI  - Chemoenzymatic synthesis and in situ application of S-adenosyl-L-methionine
      analogs.
AB  - Analogs of S-adenosyl-L-methionine (SAM) are increasingly applied to the
      methyltransferase (MT) catalysed modification of biomolecules including proteins,
      nucleic acids, and small molecules. However, SAM and its analogs suffer from an
      inherent instability, and their chemical synthesis is challenged by low yields
      and difficulties in stereoisomer isolation and inhibition. Here we report the
      chemoenzymatic synthesis of a series of SAM analogs using wild-type (wt) and
      point mutants of two recently identified halogenases, SalL and FDAS. Molecular
      modelling studies are used to guide the rational design of mutants, and the
      enzymatic conversion of L-Met and other analogs into SAM analogs is demonstrated.
      We also apply this in situ enzymatic synthesis to the modification of a small
      peptide substrate by protein arginine methyltransferase 1 (PRMT1). This technique
      offers an attractive alternative to chemical synthesis and can be applied in situ
      to overcome stability and activity issues.

PMID- 24100406
TI  - Quality of life 12 years after on-pump and off-pump coronary artery bypass
      grafting.
AB  - OBJECTIVE: To assess whether the use of either the on-pump or the off-pump method
      affects changes in health-related quality of life (QOL) in the long term after
      coronary artery bypass graft (CABG) surgery. METHODS: Four hundred and fifty-two
      (89.0%) of the 508 patients in a single institution were operated on-pump and 56
      (11.0%) were operated off-pump. The RAND-36 Health Survey (RAND-36) was used as
      an indicator of QOL. Assessments were performed preoperatively and repeated 1
      year and 12 years later. Symptomatic status was estimated according to New York
      Heart Association class. RESULTS: After 1 year, on-pump patients improved
      significantly (P<0.001) in all eight RAND-36 dimensions. Also, in off-pump
      patients, positive changes were observed in all RAND-36 dimensions and these
      changes were statistically significant (P<0.05) in six dimensions. Despite an
      ongoing decrease in QOL over the 12-year follow-up, on-pump patients still
      maintained a significant (P<0.05) improvement in all and off-pump patients in
      seven out of eight RAND-36 dimensions. A highly significant (P<0.001) pattern of
      change after 1 year was observed in the RAND-36 Mental Component Summary and
      Physical Component Summary scores in both operative groups, and despite the
      general declining trend, significant improvement was maintained during the 12
      year follow-up time. Both groups showed almost identical relief from anginal
      symptoms at 12 years. CONCLUSION: A majority of patients experience significant
      improvement in health-related QOL in the long term after CABG. Cardiopulmonary
      bypass has no impact on patients' subsequent health-related QOL.

PMID- 24100403
TI  - Targeting co-stimulatory pathways: transplantation and autoimmunity.
AB  - The myriad of co-stimulatory signals expressed, or induced, upon T-cell
      activation suggests that these signalling pathways shape the character and
      magnitude of the resulting autoreactive or alloreactive T-cell responses during
      autoimmunity or transplantation, respectively. Reducing pathological T-cell
      responses by targeting T-cell co-stimulatory pathways has met with therapeutic
      success in many instances, but challenges remain. In this Review, we discuss the
      T-cell co-stimulatory molecules that are known to have critical roles during T
      cell activation, expansion, and differentiation. We also outline the functional
      importance of T-cell co-stimulatory molecules in transplantation, tolerance and
      autoimmunity, and we describe how therapeutic blockade of these pathways might be
      harnessed to manipulate the immune response to prevent or attenuate pathological
      immune responses. Ultimately, understanding the interplay between individual co
      stimulatory and co-inhibitory pathways engaged during T-cell activation and
      differentiation will lead to rational and targeted therapeutic interventions to
      manipulate T-cell responses and improve clinical outcomes. 

PMID- 24100407
TI  - Noise intensity-intensity correlations and the fourth cumulant of photo-assisted
      shot noise.
AB  - We report the measurement of the fourth cumulant of current fluctuations in a
      tunnel junction under both dc and ac (microwave) excitation. This probes the non
      Gaussian character of photo-assisted shot noise. Our measurement reveals the
      existence of correlations between noise power measured at two different
      frequencies, which corresponds to two-mode intensity correlations in optics. We
      observe positive correlations, i.e. photon bunching, which exist only for certain
      relations between the excitation frequency and the two detection frequencies,
      depending on the dc bias of the sample. 

PMID- 24100408
TI  - Kinetic resolution of racemic alpha-hydroxyphosphonates by asymmetric
      esterification using achiral carboxylic acids with pivalic anhydride and a chiral
      acyl-transfer catalyst.
AB  - A practical protocol is developed to directly provide chiral alpha
      acyloxyphosphonates and alpha-hydroxyphosphonates from (+/-)-alpha
      hydroxyphosphonates utilizing the transacylation process to generate the mixed
      anhydrides from acid components and pivalic anhydride in the presence of
      organocatalysts (s-value = 33-518). 

PMID- 24100409
TI  - Prevalence rates of male and female sexual violence perpetrators in a national
      sample of adolescents.
AB  - IMPORTANCE Sexual violence can emerge in adolescence, yet little is known about
      youth perpetrators-especially those not involved with the criminal justice
      system. OBJECTIVE To report national estimates of adolescent sexual violence
      perpetration and details of the perpetrator experience. DESIGN, SETTING, AND
      PARTICIPANTS Data were collected online in 2010 (wave 4) and 2011 (wave 5) in the
      national Growing Up With Media study. Participants included 1058 youths aged 14
      to 21 years who at baseline read English, lived in the household at least 50% of
      the time, and had used the Internet in the last 6 months. Recruitment was
      balanced on youths' biological sex and age. MAIN OUTCOMES AND MEASURES Forced
      sexual contact, coercive sex, attempted rape, and completed rape. RESULTS Nearly
      1 in 10 youths (9%) reported some type of sexual violence perpetration in their
      lifetime; 4% (10 females and 39 males) reported attempted or completed rape.
      Sixteen years old was the mode age of first sexual perpetration (n = 18 [40%]).
      Perpetrators reported greater exposure to violent X-rated content. Almost all
      perpetrators (98%) who reported age at first perpetration to be 15 years or
      younger were male, with similar but attenuated results among those who began at
      ages 16 or 17 years (90%). It is not until ages 18 or 19 years that males (52%)
      and females (48%) are relatively equally represented as perpetrators. Perhaps
      related to age at first perpetration, females were more likely to perpetrate
      against older victims, and males were more likely to perpetrate against younger
      victims. Youths who started perpetrating earlier were more likely than older
      youths to get in trouble with caregivers; youths starting older were more likely
      to indicate that no one found out about the perpetration. CONCLUSIONS AND
      RELEVANCE Sexual violence perpetration appears to emerge earlier for males than
      females, perhaps suggesting different developmental trajectories. Links between
      perpetration and violent sexual media are apparent, suggesting a need to monitor
      adolescents' consumption of this material. Victim blaming appears to be common,
      whereas experiencing consequences does not. There is therefore urgent need for
      school programs that encourage bystander intervention as well as implementation
      of policies that could enhance the likelihood that perpetrators are identified. 

PMID- 24100410
TI  - Regulation of potato tuber sprouting.
AB  - Following tuber induction, potato tubers undergo a period of dormancy during
      which visible bud growth is inhibited. The length of the dormancy period is under
      environmental, physiological and hormonal control. Sucrose availability is one
      prerequisite for bud break. In the absence of sucrose, no bud break occurs. Thus,
      sucrose is likely to serve as nutrient and signal molecule at the same time. The
      mode of sucrose sensing is only vaguely understood, but most likely involves
      trehalose-6-phosphate and SnRK1 signalling networks. This conclusion is supported
      by the observation that ectopically manipulation of trehalose-6-phosphate levels
      influences the length of the dormancy period. Once physiological competence is
      achieved, sprouting is controlled by the level of phytohormones. Two
      phytohormones, ABA and ethylene, are supposed to suppress tuber sprouting;
      however, the exact role of ethylene remains to be elucidated. Cytokinins and
      gibberellins are required for bud break and sprout growth, respectively. The
      fifth classical phytohormone, auxin, seems to play a role in vascular
      development. During the dormancy period, buds are symplastically isolated, which
      changes during bud break. In parallel to the establishment of symplastic
      connectivity, vascular tissue develops below the growing bud most likely to
      support the outgrowing sprout with assimilates mobilised in parenchyma cells.
      Sprouting leads to major quality losses of stored potato tubers. Therefore,
      control of tuber sprouting is a major objective in potato breeding. Although
      comparative transcriptome analysis revealed a large number of genes
      differentially expressed in growing versus dormant buds, no master-regulator of
      potato tuber sprouting has been identified so far. 

PMID- 24100411
TI  - Deep brain stimulation of the anterior cingulate cortex: targeting the affective
      component of chronic pain.
AB  - Deep brain stimulation (DBS) has shown promise for relieving nociceptive and
      neuropathic symptoms of refractory chronic pain. We assessed the efficacy of a
      new target for the affective component of pain, the anterior cingulate cortex
      (ACC). A 49-year-old man with neuropathic pain underwent bilateral ACC DBS.
      Patient-reported outcome measures were collected before and 2 years after surgery
      using a Visual Analogue Scale, Short-Form 36 quality of life survey, McGill pain
      questionnaire, EuroQol-5D questionnaires (EQ-5D; Health State) and
      neuropsychological assessments. The patient improved with DBS. Two years after
      surgery, the Visual Analogue Scale decreased from 6.7 to 3.0, McGill pain
      questionnaire improved by 42% and EQ-5D Health State increased by 150%.
      Stimulating the ACC at 130 Hz, 330 us and 3 V facilitated neuropathic pain
      relief. The DBS remained efficacious during the 2-year follow-up period.
      Affective ACC DBS can relieve chronic neuropathic pain refractory to
      pharmacotherapy and restore quality of life. 

PMID- 24100412
TI  - Motor cortex-induced plasticity by noninvasive brain stimulation: a comparison
      between transcranial direct current stimulation and transcranial magnetic
      stimulation.
AB  - The aim of this study was to test and compare the effects of a within-subject
      design of repetitive transcranial magnetic stimulation (rTMS) [coupled with sham
      transcranial direct current stimulation (tDCS)] and tDCS (coupled with sham rTMS)
      on the motor cortex excitability and also compare the results against sham
      tDCS/sham rTMS. We conducted a double-blinded, randomized, sham-controlled, cross
      over trial. Eleven right-handed, healthy individuals (five women, mean age: 39.8
      years, SD 13.4) received the three interventions (cross-over design) in a
      randomized order: (a) high-frequency (HF) rTMS (+sham tDCS), (b) anodal tDCS
      (+sham rTMS), and (c) sham stimulation (sham rTMS+sham tDCS). Cortical
      excitability measurements [motor threshold, motor evoked potential (MEP),
      intracortical facilitation and inhibition, and transcallosal inhibition] and
      motor behavioral assessments were used as outcome measures. Between-group
      analysis of variance showed that MEP amplitude after HF rTMS was significantly
      higher than MEP amplitude after anodal tDCS (P=0.001). Post-hoc analysis showed a
      significant increase in MEP amplitude after HF rTMS (25.3%, P=0.036) and a
      significant decrease in MEP amplitude after anodal tDCS (-32.7%, P=0.001). There
      was a similar increase in motor function as indexed by Jebsen-Taylor Hand
      Function Test in the two active groups compared with sham stimulation. In
      conclusion, here, we showed that although both techniques induced similar motor
      gains, they induce opposing results in cortical excitability. HF rTMS is
      associated with an increase in corticospinal excitability, whereas 20 min of tDCS
      induces the opposite effect. We discuss potential implications of these results
      to future clinical experiments using rTMS or tDCS for motor function enhancement.

PMID- 24100414
TI  - The crucial role of a Ni(I) intermediate in Ni-catalyzed carboxylation of aryl
      chloride with CO2: a theoretical study.
AB  - In Ni(0)-catalyzed carboxylation reaction of aryl chloride with CO2, the
      formation of a Ni(I) species is crucial, because the CO2 insertion into the Ni(I)
      Ph bond easily occurs but that into the Ni(II)-Ph bond cannot. This is a key
      point of this successful carboxylation reaction.

PMID- 24100413
TI  - Involvement of ER stress in apoptosis induced by sialic acid-binding lectin
      (leczyme) from bullfrog eggs.
AB  - Sialic-acid binding lectin (SBL) isolated from bullfrog (Rana catesbeiana)
      oocytes is a multifunctional protein which has lectin activity, ribonuclease
      activity and cancer-selective antitumor activity. It has been reported that SBL
      induces apoptosis accompanied by rigid mitochondrial perturbation, which
      indicates mediation of the intrinsic pathway. However, the mechanism of the
      antitumor effect of SBL has not been fully elucidated. We report, here, that ER
      stress is evoked in SBL-treated cells. We show that caspase-4, an initiator
      caspase of ER stress-mediated apoptosis was activated, and inhibition of caspase
      4 resulted in significant attenuation of apoptosis induced by SBL. We analyzed
      the precise mechanism of activation of the caspase cascade induced by SBL, and
      found that caspase-9 and -4 are activated upstream of activation of caspase-8.
      Further study revealed that SBL induces the mitochondrial and ER stress-mediated
      pathways independently. It is noteworthy that SBL can induce cancer-selective
      apoptosis by multiple apoptotic signaling pathways, and it can serve as a
      candidate molecule for anticancer drugs in a novel field.

PMID- 24100415
TI  - Probing the mobility of ibuprofen confined in MCM-41 materials using MAS-PFG NMR
      and hyperpolarised-(129)Xe NMR spectroscopy.
AB  - The continuous-flow hyperpolarised (HP)-(129)Xe NMR and magic angle spinning
      pulsed field gradient (MAS-PFG) NMR techniques have been used for the first time
      to study the distribution and the dynamics of ibuprofen encapsulated in MCM-41
      with two different pore diameters. 

PMID- 24100417
TI  - Laminar MoS2 membranes for molecule separation.
AB  - For the first time, a laminar separation membrane was assembled from atom-thick
      MoS2 sheets and exhibited a water permeance of 245 L h(-1) m(-2) bar(-1), which
      was 3-5 times higher than that of graphene oxide membranes without degradation of
      the rejection ratio (89%) for Evans blue molecules. 

PMID- 24100416
TI  - Glutamate release from astrocyte cell-line GL261 via alterations in the
      intracellular ion environment.
AB  - Astrocytes modify and maintain neural activity and functions via gliotransmitter
      release such as, glutamate. They also change their properties and functions in
      response to alterations of ion environment resulting from neurotransmission;
      however, the direct evidence for whether intracellular ion alteration in
      astrocytes triggers gliotransmitter release is not indicated. Recent studies have
      reported that channelrhodopsin-2 (ChR2) is useful for alteration of intracellular
      ion environment in several types of cells with blue light exposure. Here, we show
      that ChR2-expressing GL261 (GLChR2) cells, clonal astrocytes, change their
      properties by photo-activation. Increased intracellular sodium and calcium ion
      concentrations and an altered membrane potential were observed in GLChR2 cells
      with blue light exposure. Alterations in the intracellular ion environment caused
      intracellular acidification and the inhibition of proliferation. In addition, it
      triggered glutamate release from GLChR2 cells. Glutamate from GLChR2 cells acted
      on N18 cells, clonal neuronal cells, as both a transmitter and neurotoxin
      depending on photo-activation. Our results show that the properties of ChR2
      expressing astrocytes can be controlled by blue light exposure, and cation influx
      through photo-activated ChR2 might trigger functional cation influx via
      endogenous channels and result in the increase of glutamate release. Further, our
      results suggest that ChR2-expressing glial cells could become a useful tool in
      understanding the roles of glial cell activation and neural communication in the
      regulation of brain functions. 

PMID- 24100418
TI  - Enhanced filopodium formation and stem-like phenotypes in a novel metastatic head
      and neck cancer cell model.
AB  - Head and neck squamous cell carcinoma (HNSCC) is the sixth most common cancer in
      the world, and metastasis is the major cause of cancer-related mortality.
      Prevention or elimination of metastasis may improve the survival of cancer
      patients; however, the availability of systemic HNSCC cell model with which to
      investigate the mechanisms of metastasis is limited. In the present study, we
      established a set of metastatic cell lines from HNSCC cells. In combination with
      their low-tumorigenic and high-tumorigenic ancestor cell lines, a cell model
      containing cell lines with varying malignant characteristics was established.
      Transcriptome analysis revealed distinct signatures among the metastatic cell
      lines, in comparison to the ancestor cell lines. Signaling of GTPase RhoA and
      mammalian embryonic stem cell pluripotency were identified in the metastatic
      cells. Moreover, we examined the expression of genes related to epithelial
      mesenchymal transition (EMT) (Snail, Slug, Twist, vimentin and fibronectin) and
      stemness (Oct4, Nanog and Bmi1). The capabilities of the cells for migration,
      invasion, spheroid formation and pulmonary colonization in nude mice were
      determined. Together, we demonstrated gain of Slug expression, filopodium
      formation and stem-like properties in metastatic HNSCC cells, rendering this
      model a powerful tool for the development of diagnostic biomarkers and
      identification of therapeutic targets for HNSCC.

PMID- 24100419
TI  - Ultrafine silver nanoparticles obtained from ethylene glycol at room temperature:
      catalyzed by tungstate ions.
AB  - Ethylene glycol (EG) has been widely utilized to fabricate silver nanoparticles
      with uniform size and morphology. However, the majority of the work reported to
      date using EG routinely require not only heating, but also a surfactant. In the
      present paper, we report a surfactant-free and facile method for the synthesis of
      fairly monodisperse smaller silver nanoparticles (~6 nm) through the reaction of
      silver ions with EG by using tungstates (such as potassium tungstate, sodium
      tungstate) as catalysts at room temperature. Particularly, in this method,
      tungstates as catalysts can dramatically speed up the reduction of silver ions,
      and EG acts as both a solvent and a reducing agent to reduce silver ions to Ag
      metal. Meantime, we have carried out a series of experiments to investigate the
      performance of the as-prepared silver nanoparticles. It was found that the silver
      nanoparticles show excellent catalytic activity for the reduction of 4
      nitrophenol in the presence of NaBH4.

PMID- 24100420
TI  - Tumor necrosis factor receptor associated factor-4: an adapter protein
      overexpressed in metastatic prostate cancer is regulated by microRNA-29a.
AB  - The tumor necrosis factor receptor (TNFR)-associated factor 4 (TRAF4) is a member
      of TRAF family proteins that act as major signal transducers of the TNF receptor
      and the interleukin-1 receptor/Toll-like receptor (IL-1R/TLR) superfamily. TRAF4
      has been reported to be overexpressed in various human cancers. However, the
      exact mechanisms that regulate the expression of TRAF4 still remain elusive. The
      objective of the present study was to investigate the regulatory mechanism of
      TRAF4 expression in prostate cancer. We initially identified microRNA-29a (miR
      29a) as a possible candidate to bind TRAF4 3' untranslated region (3'UTR) by the
      algorithm, TargetScan. The expression of TRAF4 mRNA and protein was inversely
      associated with miR-29a expression in prostate cancer cell lines (LNCaP, DU145
      and PC3). TRAF4 expression was reduced by the introduction of mimic miR-29a in
      LNCaP cells. Luciferase activity from the construct harboring wild-type TRAF4
      3'UTR was reduced by the mimic miR-29a and this reduction was diminished by
      introducing mutations at the predicted miR-29a binding site. On the other hand,
      TRAF4 was upregulated when transfected with the inhibitor of miR-29a in DU145 and
      PC3 cells. TRAF4 was significantly upregulated in patients with metastatic
      prostate cancer compared to those with localized prostate cancer. Furthermore,
      there was a significant inverse correlation between TRAF4 and miR-29a expression
      in tumor tissues from radical prostatectomy. Considered together, our results
      suggest that the tumor suppressor microRNA, miR-29a, is one of the regulators of
      TRAF4 expression in metastatic prostate cancer. 

PMID- 24100421
TI  - Unveiling the longitudinal association between short sleep duration and the
      incidence of obesity: the Penn State Cohort.
AB  - OBJECTIVE: Several epidemiologic, longitudinal studies have reported that short
      sleep duration is a risk factor for the incidence of obesity. However, the vast
      majority of these studies used self-reported measures of sleep duration and did
      not examine the role of objective short sleep duration, subjective sleep
      disturbances and emotional stress. DESIGN: Longitudinal, population-based study.
      SUBJECTS: We studied a random sample of 815 non-obese adults from the Penn State
      Cohort in the sleep laboratory for one night using polysomnography (PSG) and
      followed them up for a mean of 7.5 years. Subjective and objective measures of
      sleep as well as emotional stress were obtained at baseline. Obesity was defined
      as a body mass index (BMI) >=30 kg/ m(-2). RESULTS: The incidence of obesity was
      15% and it was significantly higher in women and in individuals who reported
      sleep disturbances, shorter sleep duration and higher emotional stress.
      Significant mediating effects showed that individuals with subjective sleep
      disturbances who developed obesity reported the shortest sleep duration and the
      highest emotional stress, and that subjective sleep disturbances and emotional
      stress were independent predictors of incident obesity. Further analyses revealed
      that the association between short sleep duration, subjective sleep disturbances
      and emotional stress with incident obesity was stronger in young and middle-age
      adults. Objective short sleep duration was not associated with a significantly
      increased risk of incident obesity. CONCLUSION: Self-reported short sleep
      duration in non-obese individuals at risk of developing obesity is a surrogate
      marker of emotional stress and subjective sleep disturbances. Objective short
      sleep duration is not associated with a significant increased risk of incident
      obesity. The detection and treatment of sleep disturbances and emotional stress
      should become a target of our preventive strategies against obesity.

PMID- 24100422
TI  - Response to 'Post-exercise energy load and activities may affect subsequent ad
      libitum energy intake'.

PMID- 24100423
TI  - The effects of NAMPT haplotypes and metabolic risk factors on circulating
      visfatin/NAMPT levels in childhood obesity.
AB  - OBJECTIVE: Polymorphisms in the NAMPT gene, which encodes the adipocytokine
      visfatin/nicotinamide phosphorybosil transferase (NAMPT), affect the circulating
      visfatin/NAMPT levels and are associated with obesity and cardiovascular
      diseases. However, no study has tested the hypothesis that NAMPT haplotypes could
      affect visfatin/NAMPT levels in case of childhood obesity. We investigated the
      effects of traditional metabolic risk factors (MRFs) and NAMPT polymorphisms T/C
      (rs1319501) and A/G (rs3801266) or haplotypes on visfatin/NAMPT levels in obese
      children and adolescents, and whether NAMPT polymorphisms and/or haplotypes are
      associated with susceptibility to childhood obesity. METHODS: We studied 175
      control, 99 obese and 82 obese with ? 3 MRFs children and adolescents. Genotypes
      were determined by a Taqman allele discrimination assay and real-time PCR. The
      plasma visfatin/NAMPT level was measured using an enzyme immunoassay. RESULTS:
      Obese children and adolescents with ? 3 MRFs had higher plasma visfatin/NAMPT
      levels in comparison with control children and adolescents (P<0.05). Although
      positive associations were observed between visfatin/NAMPT and body mass index
      (rs = 0.157; P = 0.034) as well as visfatin/NAMPT and waist circumference (rs =
      0.192; P = 0.011), visfatin/NAMPT and high-density lipoprotein cholesterol were
      inversely associated (rs = -0.162; P = 0.031). No significant differences in
      genotype, allele or haplotype frequency distributions for the studied
      polymorphisms were found when the three groups were compared. However, higher
      plasma visfatin/NAMPT levels were found in control and obese subjects carrying
      the GG genotype for the A/G (rs3801266) polymorphism (P<0.05) but not in obese
      children with ? 3 MRFs. Moreover, control subjects carrying the 'T-G' haplotype
      showed higher plasma visfatin/NAMPT levels. NAMPT genotypes or haplotypes were
      not associated with childhood obesity. CONCLUSIONS: Obesity in children with ? 3
      MRFs increases plasma visfatin/NAMPT levels, and this marker was associated with
      body mass index and waist circumference. The A/G polymorphism and NAMPT
      haplotypes affect plasma visfatin/NAMPT levels in controls but not in obese
      children with ? 3 MRFs. These results suggest that obesity and MRFs are more
      influential than genetic polymorphisms in the determination of visfatin/NAMPT
      levels in obese children. Further research is necessary to explain why the GG
      genotype is not associated with increased visfatin/NAMPT levels in obese children
      with ? 3 MRFs.

PMID- 24100424
TI  - Adipocyte telomere length associates negatively with adipocyte size, whereas
      adipose tissue telomere length associates negatively with the extent of fibrosis
      in severely obese women.
AB  - Telomere length can be considered as a biological marker for cell proliferation
      and aging. Obesity is associated with adipocyte hypertrophy and proliferation as
      well as with shorter telomeres in adipose tissue. As adipose tissue is a mixture
      of different cell types and the cellular composition of adipose tissue changes
      with obesity, it is unclear what determines telomere length of whole adipose
      tissue. We aimed to investigate telomere length in whole adipose tissue and
      isolated adipocytes in relation to adiposity, adipocyte hypertrophy and adipose
      tissue inflammation and fibrosis. Telomere length was measured by real-time PCR
      in visceral adipose tissue, and isolated adipocytes of 21 obese women with a
      waist ranging from 110 to 147 cm and age from 31 to 61 years. Telomere length in
      adipocytes was shorter than in whole adipose tissue. Telomere length of
      adipocytes but not whole adipose tissue correlated negatively with waist and
      adipocyte size, which was still significant after correction for age. Telomere
      length of whole adipose tissue associated negatively with fibrosis as determined
      by collagen content. Thus, in extremely obese individuals, adipocyte telomere
      length is a marker of adiposity, whereas whole adipose tissue telomere length
      reflects the extent of fibrosis and may indicate adipose tissue dysfunction. 

PMID- 24100425
TI  - Reflections of a nurses' personal experience as a loved one and a patient: the
      human side of healthcare.
AB  - One thing is for certain: healthcare is ever evolving during these challenging
      times. In this current arena of electronic medical records and regulatory bodies,
      nursing finds itself placing increasing emphasis on numbers and percentile
      rankings as a gauge of its performance. Although this information is vitally
      important as the focus centers on patient safety and quality outcomes, perhaps in
      the quest for excellent report cards, there needs to be a reminder of what is at
      the foundation of the nursing profession: communication and caring. The
      experience of a nurse as a family member, patient, and healthcare provider gives
      us the 360-degree view of this challenge. 

PMID- 24100426
TI  - What to do when the family cannot agree to withdraw life support.
AB  - This article describes a family who could not agree to withdraw life support from
      a ventilator-dependent woman who was unresponsive and whose death was inevitable.
      Evidence-based recommendations are given and resources identified to assist
      critical care nurses to facilitate discussions among family members who disagree
      about end-of-life care and to help nurses discuss end-of-life orders, address
      cultural issues, manage family conflict, assist families to make decisions, and
      act with moral courage and ethical humility when supporting families and each
      other during withdrawal of life support. 

PMID- 24100428
TI  - Use of simulation to practice multidisciplinary anaphylaxis management.
AB  - Multidisciplinary clinical simulation can be an essential part of nursing
      education strategies to improve and enhance patient safety and experience.
      Clinical simulation can be utilized to change practice, reinforce practices, and
      direct patient and family education needs for a safe discharge. Anaphylaxis is
      potentially fatal and is increasing in occurrence. A simulation scenario was
      designed by a multidisciplinary team to review anaphylaxis recognition and to
      provide simulated practice for emergency response. Clinical scenarios were
      developed based on evidence-based practices and included a prebriefing and
      postdebriefing. Bandura's self-efficacy theory was used as a framework to develop
      the project, as it supports behavior change strategies well suited for clinical
      simulation. Clinical simulations provide a nonthreatening environment for staff
      to learn, practice, and receive feedback to improve patient care and serve as a
      vehicle to role-play expected practices, enhance communication between
      disciplines, demonstrate progress, and evaluate competency. 

PMID- 24100430
TI  - Critical care visitation: nurse and family preference.
AB  - PURPOSE: The purpose of the study was to explore the satisfaction of patients'
      families and nurses with visitation guidelines in the 5 critical care units at a
      435-bed acute care hospital in the southeastern part of the United States.
      PROBLEM STATEMENT: The restriction of visitation hours for intensive care unit
      patients has significant implications for the health and well-being of the
      patient and their family. Although traditionally both facilities and staff have
      cited reasons to restrict family visitation, research indicates that these
      practices may have a detrimental effect on the overall health of the patient.
      METHODS: A descriptive correlational design is utilized in this study. Subjects
      consisted of family members of patients in 1 of the 5 critical care units and
      nurses providing care in these units. Family and nurses completed a questionnaire
      on their perspective of the critical care visiting hours. RESULTS: The majority
      of families visiting patients in the critical care setting followed the posted
      guidelines and were very satisfied with the guidelines. The hours most convenient
      for families to visit at the bedside were from 4 to 8 PM. The majority of nurses
      wanted to keep visiting hours during day-shift hours; family members were divided
      on having all hours available for visitation. Nurses had varied perspectives on
      whether visitation should be allowed as a restraint alternative, when family is
      out of town, patient emotional needs, eminent death, at time of discharge
      instructions, and to speak with a physician. CLINICAL IMPLICATIONS: Family member
      visitation in the intensive care unit setting should be flexible and open. This
      may include tailoring a plan on admission with the family to allow open access to
      the patient during times when they are most available; thus, each family has a
      plan that suits its unique dynamics.

PMID- 24100432
TI  - Prevention of unplanned intensive care unit admissions and hospital mortality by
      early warning systems.
AB  - Researchers have found that patients exhibit physiological changes up to 8 hours
      prior to an arrest event. Deaths have been attributed to a lack of observation,
      lack of documentation of observations, inability of a caregiver to recognize
      early signs of deterioration, and lack of communication between healthcare
      providers. This integrative review examines early warning scoring systems and
      their effectiveness in predicting a patient's potential for deterioration and
      considers whether these scoring systems prevent unplanned intensive care unit
      admissions and/or death. Three databases (MEDLINE, CINAHL [Cumulative Index to
      Nursing and Allied Health Literature], and the Cochrane Collaboration) were
      searched to identify the instruments and clinical support systems available to
      assist healthcare personnel in recognizing early clinical deterioration. Key
      search words included modified early warning score, early warning score, early
      warning systems, deteriorating patient, patients at risk, shock index, track and
      trigger systems, and failure to rescue. Two prior literature reviews examined
      early warning scoring systems and their effects on patient outcomes; however, the
      most recent one reviewed only articles published before 2007. This review
      examined studies of early warning systems and the incorporation of clinical
      support published from 2007 to 2012. Nine studies fitting the search criteria
      were included in this review. Early warning scoring systems that interface with
      electronic medical records and are supplemented with decision aides (algorithms)
      and clinical support systems produce an effective screening system for early
      identification of deteriorating patients. This multifaceted approach decreases
      unplanned intensive care unit admissions and hospital mortality. 

PMID- 24100433
TI  - Using the synergy model of patient care in understanding the lived emergency
      department experiences of patients, family members and their nurses during
      critical illness: a phenomenological study.
AB  - Despite many studies conducted aimed to understand and improve emergency care,
      research on the triad of nurses, patients, and family members looking at the
      lived emergency department experiences and their perspective of each from the
      other is notably absent. In a hermeneutic phenomenological study using van
      Manen's method, a sample of 10 patients, 5 family members, and 8 nurses of a
      nonprofit community hospital was recruited and interviewed in 2010 to 2011 to
      explore, understand, and describe their lived experiences during critical illness
      in the emergency department. The nurses perceived that addressing the patient's
      physiologic deficit promptly is vital in the emergency department as well as
      including family members as coparticipants in the care. Patients and family
      members perceived that communication, critical thinking, sensitivity, and caring
      are essential for emergency department nurses. The American Association of
      Critical-Care Nurses' Synergy Model for Patient Care was applied in
      conceptualizing the findings and served as a framework in recommending practices
      and interventions geared toward improving competencies required in caring for
      critically ill patients and their families in the emergency department. The study
      supports recognizing the patient and family as active participants in the
      patient's medical care; encouraging family-member presence and creating
      institutional policies for patient- and family-centered care, as well as
      encouraging the development of ongoing programs that will recognize, enhance, and
      support the psychological and emotional well-being of emergency department
      nurses. 

PMID- 24100435
TI  - Peer review: why we need nurse leaders to serve as reviewers for nursing
      publications.

PMID- 24100436
TI  - Motor neuron disease: Multifocal initiation and local propagation model of ALS.

PMID- 24100438
TI  - Reversible insulator-metal transition of LaAlO3/SrTiO3 interface for nonvolatile
      memory.
AB  - We report a new type of memory device based on insulating LaAlO3/SrTiO3 (LAO/STO)
      hetero-interface. The microstructures of the LAO/STO interface are characterized
      by Cs-corrected scanning transmission electron microscopy, which reveals the
      element intermixing at the interface. The inhomogeneous element distribution may
      result in carrier localization, which is responsible for the insulating state.
      The insulating state of such interface can be converted to metallic state by
      light illumination and the metallic state maintains after light off due to giant
      persistent photoconductivity (PPC) effect. The on/off ratio between the PPC and
      the initial dark conductance is as large as 105. The metallic state also can be
      converted back to insulating state by applying gate voltage. Reversible and
      reproducible resistive switching makes LAO/STO interface promising as a
      nonvolatile memory. Our results deepen the understanding of PPC phenomenon in
      LAO/STO, and pave the way for the development of all-oxide electronics
      integrating information storage devices.

PMID- 24100437
TI  - A comparative study of affibody, panitumumab, and EGF for near-infrared
      fluorescence imaging of EGFR- and EGFRvIII-expressing tumors.
AB  - Aberrant overexpression and/or activation of epidermal growth factor receptor
      (EGFR) is associated with many types of cancers. EGFR variant III (EGFRvIII) is a
      common in-frame deletion mutant, which lacks a large part of the extracellular
      portion (exons 2-7), including components of the ligand-binding domain. Although
      EGFR has been extensively studied as a molecular imaging target, information
      about EGFRvIII-targeted molecular imaging is lacking. In this study, the EGFR
      specific affibody, therapeutic antibody panitumumab, and ligand EGF were labeled
      with IRDye 800CW (Ex/Em: 774/789 nm), yielding Aff800, Pan800, and EGF800,
      respectively. The binding affinities of the labeled agents were compared in cell
      based assays using a rat glioma cell line F98 parental (F98-p) lacking EGFR
      expression, and 2 F98-derived transgenic cell lines expressing EGFR or EGFRvIII
      (designated as F98-EGFR and F98-vIII, respectively). Results showed that all
      agents could bind to F98-EGFR, with Pan800 having the highest binding affinity,
      followed by Aff800 and EGF800. Pan800 and Aff800, but not EGF800, also bound to
      F98-vIII. In vivo animal imaging demonstrated that compared with F98-p tumors,
      F98-EGFR tumors generated higher signals with all three agents. However, in the
      case of F98-vIII, only Pan800 and Aff800 signals were higher. Analysis of tissue
      lysates showed that a large portion of Pan800 was degraded into small fragments
      in F98-EGFR and F98-vIII tumors, possibly due to proteolytic digestion after its
      specific binding and internalization. In conclusion, Pan800 and Aff800 could be
      used as imaging agents for both wild-type EGFR and EGFRvIII, whereas EGF800 only
      targets wild-type EGFR. 

PMID- 24100439
TI  - A liquid-phase-blocking concanavalin A enzyme-linked immunosorbent assay for the
      detection of antibodies against Newcastle disease virus in serum of free-ranging
      pigeons.
AB  - A competitive liquid-phase-blocking concanavalin A enzyme-linked immunosorbent
      assay (LPB-ConA-ELISA) was developed in the current study. The assay used ConA as
      a capture reagent, and the sera of specific pathogen-free chickens immunized with
      nonpurified Newcastle disease virus (NDV) suspension as detector antibodies, to
      detect and quantify specific antiviral antibodies in serum samples from free
      ranging pigeons. The comparison between the LPB-ConA-ELISA and the
      hemagglutination inhibition (HI) test for the detection of antibodies in serum
      samples from 107 pigeons showed significant correlation between the assays (r =
      0.875), a high sensitivity (100%), specificity (95.8%), accuracy (96.3%) for the
      ELISA, and good agreement (kappa = 0.83) between the 2 assays. The results of
      this study suggest that the LPB-ConA-ELISA could be a useful alternative to HI
      test in the serodiagnosis of NDV in pigeons, or other species of birds. 

PMID- 24100440
TI  - Probiotics to prevent or treat excessive infant crying: systematic review and
      meta-analysis.
AB  - IMPORTANCE Excessive infant crying is common, distressing, but without proven
      effective prevention or management options. Probiotics may be a promising
      solution. OBJECTIVE To examine whether probiotics are effective in the
      prevention/management of crying ("colic") in infants 3 months or younger. DATA
      SOURCES A systematic search of MEDLINE, EMBASE, and the Cochrane Library,
      supplemented by the metaRegister of Controlled Trials. STUDY SELECTION Studies
      that randomized infants 3 months or younger to oral probiotics vs placebo or no
      or standard treatment with the outcome of infant crying, measured as the duration
      or number of episodes of infant crying/distress or diagnosis of "infant colic."
      Twelve of the 1180 initially identified studies were selected. DATA EXTRACTION
      AND SYNTHESIS This review/meta-analysis was conducted according to guidelines
      from the Cochrane Handbook for Systematic Reviews of Interventions, with
      reporting following the Preferred Reporting Items for Systematic Reviews and Meta
      analyses guidelines. Data were independently extracted by 3 of us. MAIN
      OUTCOME(S) AND MEASURE(S) Infant crying, measured as the duration or number of
      episodes of infant crying/distress, or diagnosis of "infant colic." RESULTS Of
      the 12 trials (1825 infants) reviewed, 6 suggested probiotics reduced crying, and
      6 did not. Three of the 5 management trials concluded probiotics effectively
      treat colic in breastfed babies; 1 suggested possible effectiveness in formula
      fed babies with colic, and 1 suggested ineffectiveness in breastfed babies with
      colic. Meta-analysis of 3 small trials of breastfed infants with colic found that
      Lactobacillus reuteri markedly reduced crying time at 21 days (median difference,
      -65 minutes/d; 95% CI, -86 to -44). However, all trials had potential biases.
      Meanwhile, of 7 prevention trials, 2 suggested possible benefits. Considerable
      variability in the study populations, study type, delivery mode/dose of probiotic
      supplementation, and outcomes precluded meta-analysis. CONCLUSIONS AND RELEVANCE
      Although L reuteri may be effective as treatment for crying in exclusively
      breastfed infants with colic, there is still insufficient evidence to support
      probiotic use to manage colic, especially in formula-fed infants, or to prevent
      infant crying. Results from larger rigorously designed studies applicable to all
      crying infants will help draw more definitive conclusions. 

PMID- 24100441
TI  - Approaches to the synthesis of a novel, anti-HIV active integrase inhibitor.
AB  - The novel HIV-1 integrase inhibitor 1, discovered in our laboratory, exhibits
      potent anti-HIV activity against a diverse set of HIV-1 isolates and also against
      HIV-2 and SIV. In addition, this compound displays low cellular cytotoxicity and
      possesses a favorable in vitro drug interaction profile with respect to isozymes
      of cytochrome P450 (CYP) and uridine 5'-diphospho-glucuronosyltransferase (UGT).
      However, the total synthesis of this significant HIV integrase inhibitor has not
      been reported. This contribution describes an optimized, reproducible, multi
      step, synthetic route to inhibitor 1. The yield for the separate steps averaged
      about 80%. The methodologies utilized in the synthesis were, among others, a
      palladium-catalyzed cross-coupling reaction, a crossed-Claisen condensation, and
      a hydrazino amide synthesis step. Successful alternative synthetic methodologies
      for some of the steps are also described. 

PMID- 24100442
TI  - Compound K, a metabolite of ginseng saponin, inhibits colorectal cancer cell
      growth and induces apoptosis through inhibition of histone deacetylase activity.
AB  - In this study, we investigated the molecular mechanisms underlying the anti
      proliferative effects of Compound K, with specific reference to histone
      modification. Exposure of HT-29 human colon cancer cells to Compound K resulted
      in time-dependent inhibition of histone deacetylase (HDAC) activity, mRNA and
      protein expression. Compound K treatment induced unmethylation of the RUNX3
      promoter region such as TSA treatment and an accumulation of acetylated histones
      H3 and H4 within the total cellular chromatin, resulting in an enhanced ability
      of these histones to bind to the promoter sequences of the tumor suppressor gene
      Runt-related transcription factor 3 (RUNX3). Treatment of cells with Compound K
      increased the mRNA and protein expression of RUNX3, as well as p21, a downstream
      target of RUNX3. These alterations were consistent with cell cycle arrest at the
      G0/G1 phases and induction of apoptosis. Our results provide new insights into
      the mechanisms of Compound K action in human colorectal cancer cells and suggest
      that HDAC inhibition presents a novel approach to prevent or treat colorectal
      cancer.

PMID- 24100443
TI  - Differentiation of aggressive and indolent subtypes of uterine sarcoma using
      maximum standardized uptake value.
AB  - OBJECTIVE: The aim of the study was to elucidate the differential metabolic
      activities in aggressive and indolent subtypes of uterine sarcomas, which may aid
      in managing these heterogeneous tumours. METHODS: We retrospectively analysed the
      PET/computed tomography scans of consecutive patients (N=18) diagnosed with
      uterine sarcoma at our unit. The patients were divided into indolent (N=4) and
      aggressive (N=14) tumour groups, and the maximum standardized uptake values (SUV
      max) of all lesions (n=134) were measured. The SUV max of the lesions were
      compared between the two tumour groups using the Mann-Whitney U-test. We
      calculated the optimal cutoff value as determined by receiver operating
      characteristic analysis. A P-value less than 0.05 was considered statistically
      significant. RESULTS: The mean SUV max of aggressive (n=104) and indolent tumours
      (n=30) were significantly different (8.0 +/- 7.3 vs. 1.9 +/- 0.9 respectively;
      P<0.001). A cutoff of SUV max greater than 4.0 was able to exclude indolent
      tumours, with 100% specificity and positive predictive value (sensitivity 72%,
      negative predictive value 50% and accuracy 78%; area under the curve 97%). By
      applying this same cutoff value on the most metabolic active lesion in each
      patient, we were able to correctly classify all but one patient into either the
      aggressive or indolent tumour group with 100% specificity and positive predictive
      value (sensitivity 93%, negative predictive value 80% and accuracy 94%).
      CONCLUSION: Aggressive and indolent uterine sarcoma subtypes have differential
      metabolic activities that can be used to classify them and this can aid in
      patient management for preoperative surgical planning and treatment
      stratification.

PMID- 24100444
TI  - Pilot study of 68Ga-DOTA-F(ab')2-trastuzumab in patients with breast cancer.
AB  - OBJECTIVE: 68Ga-1,4,7,10-Tetraazacyclododecane-N,N',N'',N'''-tetraacetic acid
      (DOTA)-F(ab')2-trastuzumab [68Ga-DOTA-F(ab')2-trastuzumab] has been developed at
      our institution as a positron imaging reagent for assessing human epidermal
      growth factor receptor 2 (HER2) expression status by in-vivo imaging. Initial
      studies on animals demonstrated promising results in the monitoring of treatment
      response to heat shock protein 90-targeted drugs that inhibit the client protein
      HER2. We report here our initial clinical experience in the assessment of the
      toxicity, pharmacokinetics, biodistribution, and dosimetry profile of 68Ga-DOTA
      F(ab')2-trastuzumab with PET/computed tomography using a mean of 236 MBq/5 mg
      administered intravenously. MATERIALS AND METHODS: A group of 16 women with
      breast cancer were enrolled in this study. The one patient who did not receive
      68Ga-DOTA-F(ab')2-trastuzumab was excluded from analysis. Both HER2-negative
      (n=7) and HER2-positive (n=8) cases were studied. Among the latter, seven had
      undergone trastuzumab treatment previously and one had not. RESULTS: It was
      determined that 68Ga-DOTA-F(ab')2-trastuzumab was well tolerated, with a T1/2 of
      ~ 3.6 +/- 0.9 h; the critical organ was the kidney, with a mean dose of 0.383
      cGy/37 MBq; and tumor targeting was seen in 4/8 patients with HER2-positive
      disease. CONCLUSION: The reagent is safe, and assessments through additional
      studies in a better-defined group of patients, using larger administered masses
      of antibodies, with a better immunoreactive fraction are needed.

PMID- 24100445
TI  - cAMP signaling regulates platelet myosin light chain (MLC) phosphorylation and
      shape change through targeting the RhoA-Rho kinase-MLC phosphatase signaling
      pathway.
AB  - Cyclic adenosine monophosphate (cAMP)-dependent signaling modulates platelet
      shape change through unknown mechanisms. We examined the effects of cAMP
      signaling on platelet contractile machinery. Prostaglandin E1 (PGE1)-mediated
      inhibition of thrombin-stimulated shape change was accompanied by diminished
      phosphorylation of myosin light chain (MLC). Since thrombin stimulates phospho
      MLC through RhoA/Rho-associated, coiled-coil containing protein kinase (ROCK)
      dependent inhibition of MLC phosphatase (MLCP), we examined the effects of cAMP
      on this pathway. Thrombin stimulated the membrane localization of RhoA and the
      formation of a signaling complex of RhoA/ROCK2/myosin phosphatase-targeting
      subunit 1 (MYPT1). This resulted in ROCK-mediated phosphorylation of MYPT1 on
      threonine 853 (thr(853)), the disassociation of the catalytic subunit protein
      phosphatase 1delta (PP1delta) from MYPT1 and inhibition of basal MLCP activity.
      Treatment of platelets with PGE1 prevented thrombin-induced phospho-MYPT1
      thr(853) in a protein kinase A (PKA)-dependent manner. Examination of the
      molecular mechanisms revealed that PGE1 induced the phosphorylation of RhoA on
      serine(188) through a pathway requiring cAMP and PKA. This event inhibited the
      membrane relocalization of RhoA, prevented the association of RhoA with ROCK2 and
      MYPT1, attenuated the dissociation of PP1delta from MYPT1, and thereby restored
      basal MLCP activity leading to a decrease in phospho-MLC. These data reveal a new
      mechanism by which the cAMP-PKA signaling pathway regulates platelet function. 

PMID- 24100446
TI  - Primitive CML cell expansion relies on abnormal levels of BMPs provided by the
      niche and on BMPRIb overexpression.
AB  - Leukemic stem cells in chronic phase chronic myelogenous leukemia (CP-CML) are
      responsible for disease persistence and eventual drug resistance, most likely
      because they survive, expand, and are sustained through interactions with their
      microenvironment. Bone morphogenetic proteins 2 (BMP2) and 4 (BMP4) regulate the
      fate and proliferation of normal hematopoietic stem cells, as well as
      interactions with their niche. We show here that the intrinsic expression of
      members of the BMP response pathway are deregulated in CML cells with differences
      exhibited in mature (CD34(-)) and immature (CD34(+)) compartments. These changes
      are accompanied by altered functional responses of primitive leukemic cells to
      BMP2 and BMP4 and strong increases in soluble BMP2 and BMP4 in the CML bone
      marrow. Using primary cells and a cell line mimicking CP-CML, we found that
      myeloid progenitor expansion is driven by the exposure of immature cells
      overexpressing BMP receptor Ib to BMP2 and BMP4. In summary, we demonstrate that
      deregulation of intracellular BMP signaling in primary CP-CML samples corrupts
      and amplifies their response to exogenous BMP2 and BMP4, which are abnormally
      abundant within the tumor microenvironment. These results provide new insights
      with regard to leukemic stem cell biology and suggest possibilities for the
      development of novel therapeutic tools specifically targeting the CML niche. 

PMID- 24100447
TI  - The prognostic impact of variant histology in nodular lymphocyte-predominant
      Hodgkin lymphoma: a report from the German Hodgkin Study Group (GHSG).
AB  - Nodular lymphocyte-predominant Hodgkin lymphoma (NLPHL) accounts for
      approximately 5% of all Hodgkin lymphoma cases. The aim of this study was to
      evaluate the prognostic implication of histopathologic NLPHL variants. Biopsies
      of 423 NLPHL patients treated within 9 prospective clinical trials performed by
      the German Hodgkin Study Group were classified as tumor cell-rich cases (n = 10),
      typical NLPHL (n = 308), or histopathologic variants (n = 105). Histopathologic
      variants were characterized by the presence of lymphoma cells outside the B-cell
      nodules or B-cell depletion of the microenvironment. Compared with typical NLPHL,
      histopathologic variants were associated with advanced disease (29.5% vs 14.6%, P
      = .0012) and a higher relapse rate (18.1% vs 6.5% at 5 years, P = .0009). Variant
      histology represented an independent prognostic factor (odds ratio = 2.955) in a
      multivariate model of progression/relapse. A prognostic score, including the risk
      factors variant histopathologic growth pattern, low serum albumin, and male
      gender, was derived from this model and allowed the definition of 3 distinct risk
      groups. NLPHL patients presenting with histopathologic variants have a poorer
      outcome compared with those showing typical histology. The newly developed
      prognostic score combining histologic and clinical features allows allocating
      NLPHL patients to defined risk groups. 

PMID- 24100448
TI  - Enrichment of FLI1 and RUNX1 mutations in families with excessive bleeding and
      platelet dense granule secretion defects.
AB  - We analyzed candidate platelet function disorder genes in 13 index cases with a
      history of excessive bleeding in association with a significant reduction in
      dense granule secretion and impaired aggregation to a panel of platelet agonists.
      Five of the index cases also had mild thrombocytopenia. Heterozygous alterations
      in FLI1 and RUNX1, encoding Friend leukemia integration 1 and RUNT-related
      transcription factor 1, respectively, which have a fundamental role in
      megakaryocytopoeisis, were identified in 6 patients, 4 of whom had mild
      thrombocytopenia. Two FLI1 alterations predicting p.Arg337Trp and p.Tyr343Cys
      substitutions in the FLI1 DNA-binding domain abolished transcriptional activity
      of FLI1. A 4-bp deletion in FLI1, and 2 splicing alterations and a nonsense
      variation in RUNX1, which were predicted to cause haploinsufficiency of either
      FLI1 or RUNX1, were also identified. Our findings suggest that alterations in
      FLI1 and RUNX1 may be common in patients with platelet dense granule secretion
      defects and mild thrombocytopenia. 

PMID- 24100449
TI  - Chronic lymphocytic leukemia disease progression is accelerated by APRIL-TACI
      interaction in the TCL1 transgenic mouse model.
AB  - Although in vitro studies pointed to the tumor necrosis factor family member
      APRIL (a proliferation-inducing ligand) in mediating survival of chronic
      lymphocytic leukemia (CLL) cells, clear evidence for a role in leukemogenesis and
      progression in CLL is lacking. APRIL significantly prolonged in vitro survival of
      CD5(+)B220(dull) leukemic cells derived from the murine EMU-TCL1-Tg (TCL1-Tg
      [transgenic]) model for CLL. APRIL-TCL1 double-Tg mice showed a significantly
      earlier onset of leukemia and disruption of splenic architecture, and survival
      was significantly reduced. Interestingly, clonal evolution of CD5(+)B220(dull)
      cells (judged by BCR clonality) did not seem to be accelerated by APRIL; both
      mouse strains were oligoclonal at 4 months. Although APRIL binds different
      receptors, APRIL-mediated leukemic cell survival depended on tumor necrosis
      factor receptor superfamily member 13B (TACI) ligation. These findings indicate
      that APRIL has an important role in CLL and that the APRIL-TACI interaction might
      be a selective novel therapeutic target for human CLL. 

PMID- 24100451
TI  - Electrical and optical characterization of atomically thin WS2.
AB  - Atomically thin layers of materials, which are just a few atoms in thickness,
      present an attractive option for future electronic devices. Herein we
      characterize, optically and electronically, atomically thin tungsten disulphide
      (WS2), a layered semiconductor. We provide the distinctive Raman and
      photoluminescence signatures for single layers, and prepare field-effect
      transistors where atomically thin WS2 serves as the conductive channel. The
      transistors present mobilities MU = 10 cm(2) V(-1) s(-1) and exhibit ON/OFF
      ratios exceeding 100,000. Our results show that WS2 is an attractive option for
      applications in electronic and optoelectronic devices and pave the way for
      further studies in this two-dimensional material.

PMID- 24100450
TI  - BMP-mediated specification of the erythroid lineage suppresses endothelial
      development in blood island precursors.
AB  - The developmental relationship between the blood and endothelial cell (EC)
      lineages remains unclear. In the extra-embryonic blood islands of birds and
      mammals, ECs and blood cells are closely intermixed, and blood island precursor
      cells in the primitive streak express many of the same molecular markers, leading
      to the suggestion that both lineages arise from a common precursor, called the
      hemangioblast. Cells within the blood island of Xenopus also coexpress
      predifferentiation markers of the blood and EC lineages. However, using multiple
      assays, we find that precursor cells in the Xenopus blood island do not normally
      differentiate into ECs, suggesting that classic hemangioblasts are rare or
      nonexistent in Xenopus. What prevents these precursor cells from developing into
      mature ECs? We have found that bone morphogenetic protein (BMP) signaling is
      essential for erythroid differentiation, and in the absence of BMP signaling,
      precursor cells adopt an EC fate. Furthermore, inhibition of the erythroid
      transcription pathway leads to endothelial differentiation. Our results indicate
      that bipotential endothelial/erythroid precursor cells do indeed exist in the
      Xenopus blood island, but BMP signaling normally acts to constrain EC fate. More
      generally, these results provide evidence that commitment to the erythroid
      lineage limits development of bipotential precursors toward an endothelial fate. 

PMID- 24100452
TI  - A conformation-switching fluorescent protein probe for detection of alpha
      synuclein oligomers.
AB  - We engineered the structural flexibility of an alpha synuclein (alphaS) variant,
      PG65, together with conformation-sensitive fluorescence to create a molecular
      probe for rapid, specific and quantitative detection of alphaS oligomers, which
      are the major toxic aggregate forms in Parkinson's disease. 

PMID- 24100454
TI  - Protein expression and subcellular localization of familial acute myelogenous
      leukemia-related factor.
AB  - The present study was designed to evaluate the expression and subcellular
      distribution of the familial acute myelogenous leukemia-related factor (FAMLF). A
      14-amino acid epitope of the predicted open reading frame of the FAMLF gene was
      identified using bioinformatics. This polypeptide was synthesized, conjugated to
      keyhole limpet hemocyanin and was subsequently used to produce antibodies. The
      antibody titer and specificity were characterized using ELISA and western blot
      assays, respectively. The antibody detected FAMLF protein expression in several
      human leukemia cell lines, bone marrow cells derived from one acute myeloid
      leukemia patient and one chronic myeloid leukemia patient, but not in bone marrow
      cells of healthy subjects. The FAMLF/GFP fusion protein was expressed in both the
      nucleus and the cytoplasm of transfected NIH3T3 cells. Our results demonstrate
      that the FAMLF gene is expressed in an AML patient but not in healthy controls,
      suggesting its association with AML. 

PMID- 24100453
TI  - What do infants understand of others' action? A theoretical account of early
      social cognition.
AB  - Intention reading and action understanding have been reported in ever-younger
      infants. However, the notions of intention attribution and action understanding,
      as well as their relation to each other, are surrounded by much confusion, making
      it difficult to assess the meaning and value of such findings. In this paper we
      set out to clarify the notions of 'action understanding' and 'intention
      attribution'. We will show that what is commonly referred to as 'action
      understanding' in fact encompasses various heterogeneous association and
      prediction mechanisms. In general, these forms of action understanding will not
      result in the attribution of an intention to an observed actor. By detaching
      intention attribution from action understanding, and by exposing the latter as an
      umbrella notion, we provide a theoretical framework on early social cognition
      that allows for better comparison of findings from different experimental
      paradigms, and better assessment of infant action understanding abilities. Taking
      into account the plurality of forms that action understanding can adopt will help
      cognitive neuroscience to gain a full understanding of the early roots of social
      cognition. 

PMID- 24100455
TI  - Vasculitis syndromes: Vasculitis assessments--what do patients think?

PMID- 24100458
TI  - Rheumatoid arthritis: Metabolic reprogramming of T cells in RA.

PMID- 24100460
TI  - Treatment of systemic lupus erythematosus: new therapeutic avenues and blind
      alleys.
AB  - Despite rapid accumulation of knowledge about complex immune dysregulation in
      systemic lupus erythematosus (SLE) and major primary lupus syndromes, and a
      plethora of promising new treatments reaching preclinical and early clinical
      studies, advanced-phase trials of new biologic agents have repeatedly failed to
      achieve their clinical end points. It is possible that none of these agents work,
      but the accuracy of this suggestion is as unclear as the case for efficacy, owing
      to issues in the design of studies and the opacity of the data that have
      resulted. Disease heterogeneity and complexity might be a hurdle that is simply
      too high to overcome by existing methodological approaches, and the way forward
      to interpretable trial results remains unclear. Nonetheless, well-characterized
      patterns of immune pathology are shared by substantial subsets of patients, and
      selective targeting of one or more relevant immune system molecules seems to
      offer the promise of safer and more effective treatments. Evolution dictates a
      more personalized approach to therapy and trial design, but this option seems
      challenging in the current economic, regulatory and scientific environment. This
      Review addresses these concerns by considering the progress of some of the
      investigational treatments targeting key physiological abnormalities in lupus. 

PMID- 24100462
TI  - Osteoporosis: Linking osteoporosis with Alzheimer disease.

PMID- 24100464
TI  - Effect of plyometric training on lower limb biomechanics in females.
AB  - OBJECTIVE: To verify the effects of plyometric training on lower limb kinematics,
      eccentric hip and knee torques, and functional performance. DESIGN: Cohort study.
      SETTING: Research laboratory. PARTICIPANTS: Thirty-six females were divided into
      a training group (TG; n = 18) that carried out the plyometric training for 8
      weeks, and a control group (CG; n = 18) that carried out no physical training.
      INTERVENTIONS: Twenty-four plyometric training sessions during approximately 8
      weeks with 3 sessions per week on alternate days. MAIN OUTCOMES MEASURES: Lower
      limb kinematics (maximum excursion of hip adduction, hip medial rotation, and
      knee abduction during the single leg squat), eccentric hip (abductor, adductor,
      medial, and lateral rotator) isokinetic peak torques and knee (flexor and
      extensor) isokinetic peak torques, and functional performance (triple hop test
      and the 6-m timed hop test). RESULTS: After 8 weeks, only the TG significantly
      reduced the values for the maximum excursion of knee abduction (P = 0.01) and hip
      adduction (P < 0.001). Similarly, only the TG significantly increased the
      eccentric hip abductor (P < 0.001) and adductor (P = 0.01) torques. Finally, only
      the TG significantly increased the values in the triple hop test (P < 0.001) and
      significantly decreased the values in the 6-m timed hop test (P < 0.001) after
      intervention. CONCLUSION: Plyometric training alters lower limb kinematics and
      increases eccentric hip torque and functional performance, suggesting the
      incorporation of these exercises in preventive programs for ACL injuries.

PMID- 24100465
TI  - The association between long working hours and health: a systematic review of
      epidemiological evidence.
AB  - OBJECTIVES: Many studies have investigated the association between long working
      hours and health. By focusing on differences in the definition of long working
      hours and the influence of shift work, we attempt to explain why the results of
      these studies remain inconclusive. METHODS: We defined long working hours as
      working time greater than around 40 hours per week or 8 hours per day. Since
      previous studies have indicated that shift work is detrimental to health, we
      minimized the influence of shift work in the studies. We also placed importance
      on the existence of reference groups since this made the results clearer. Based
      on these points, we analyzed previous studies to clarify the epidemiological
      evidence regarding the association between long working hours and health. We
      established inclusion criteria and carried out a systematic search for articles
      published in the Medline and PsycINFO databases between 1995-2012. RESULTS: We
      identified a total of 17 articles and 19 studies (12 prospective cohort and 7
      cross-sectional studies). The outcomes were all-cause mortality, circulatory
      disease, diabetes mellitus, metabolic syndrome, depressive state, anxiety, other
      psychological disorders, sleep condition, cognitive function, and health-related
      behavior. Long working hours had significant adverse effects on most health
      outcomes. CONCLUSIONS: We concluded that working long hours is associated with
      depressive state, anxiety, sleep condition, and coronary heart disease. However,
      further studies that appropriately deal with the definition of long working hours
      and shift work are needed.

PMID- 24100466
TI  - Overcoming paclitaxel resistance in uterine endometrial cancer using a COX-2
      inhibitor.
AB  - Cyclooxygenase (COX)-2 inhibitors have been reported to potentially modulate the
      resistance of cancer cells to chemotherapeutic drugs by affecting multidrug
      resistance 1 (MDR1) expression. In the present study, we investigated the
      association between COX-2 and MDR1 expression in endometrial cancers and
      evaluated the effects of the COX-2 inhibitor, etodolac, in combination with
      paclitaxel on paclitaxel-resistant endometrial cancer cells. The relationship
      between COX-2 and MDR1 mRNA expression was examined by quantitative PCR in 36
      endometrial cancer specimens. The paclitaxel-resistant cell line OMC-2P was
      established from OMC-2 cells. Paclitaxel (1 ug/ml) with or without etodolac (10
      ug/ml) was added to OMC-2 and OMC-2P cells, and COX-2 and MDR1 mRNA expression
      levels were examined. The concentration of prostaglandin E2 (PGE2) in the
      supernatant of each cell line was examined by enzyme-linked immunosorbent assay.
      The function of MDR1 was determined by intracellular accumulation of rhodamine
      123 using flow cytometry, and the concentration of intracellular paclitaxel was
      determined by high-performance liquid chromatography. We found a positive
      relationship between COX-2 and MDR1 mRNA expression in endometrial cancer. Both
      COX-2 mRNA expression and PGE2 production were elevated in resistant OMC-2P cells
      when compared to non-resistant OMC-2 cells. Additionally, MDR1 mRNA expression
      was markedly upregulated in OMC-2P cells. In OMC-2 cells, COX-2 and MDR1 mRNA
      levels were significantly upregulated by paclitaxel treatment and downregulated
      by co-administration with etodolac. In OMC-2P cells, COX-2 mRNA expression was
      also significantly upregulated by paclitaxel treatment and tended to be
      downregulated by co-administration with etodolac. Moreover, co-administration of
      paclitaxel and etodolac suppressed the induction of MDR1 mRNA. Rhodamine 123
      efflux was increased in OMC-2P cells when compared to the efflux in the OMC-2
      cells and was increased in response to paclitaxel treatment. Co-administration of
      paclitaxel and etodolac in both cell lines resulted in decreased rhodamine 123
      efflux. The actual concentration of intracellular paclitaxel in OMC-2P cells was
      significantly lower than that in OMC-2 cells treated with paclitaxel alone and
      was significantly increased after co-administration of paclitaxel and etodolac.
      These findings suggest that paclitaxel resistance may be associated with COX-2
      and MDR1 expression in cancer cells. Co-administration of COX-2 inhibitors and
      paclitaxel may have a key role in modulating or overcoming paclitaxel resistance
      in endometrial cancers.

PMID- 24100461
TI  - Oxidative stress in the pathology and treatment of systemic lupus erythematosus.
AB  - Oxidative stress is increased in systemic lupus erythematosus (SLE), and it
      contributes to immune system dysregulation, abnormal activation and processing of
      cell-death signals, autoantibody production and fatal comorbidities.
      Mitochondrial dysfunction in T cells promotes the release of highly diffusible
      inflammatory lipid hydroperoxides, which spread oxidative stress to other
      intracellular organelles and through the bloodstream. Oxidative modification of
      self antigens triggers autoimmunity, and the degree of such modification of serum
      proteins shows striking correlation with disease activity and organ damage in
      SLE. In T cells from patients with SLE and animal models of the disease,
      glutathione, the main intracellular antioxidant, is depleted and serine/threonine
      protein kinase mTOR undergoes redox-dependent activation. In turn, reversal of
      glutathione depletion by application of its amino acid precursor, N
      acetylcysteine, improves disease activity in lupus-prone mice; pilot studies in
      patients with SLE have yielded positive results that warrant further research.
      Blocking mTOR activation in T cells could conceivably provide a well-tolerated
      and inexpensive alternative approach to B-cell blockade and traditional
      immunosuppressive treatments. Nevertheless, compartmentalized oxidative stress in
      self-reactive T cells, B cells and phagocytic cells might serve to limit
      autoimmunity and its inhibition could be detrimental. Antioxidant therapy might
      also be useful in ameliorating damage caused by other treatments. This Review
      thus seeks to critically evaluate the complexity of oxidative stress and its
      relevance to the pathogenesis and treatment of SLE. 

PMID- 24100467
TI  - Developmental and physiological challenges of octopus (Octopus vulgaris) early
      life stages under ocean warming.
AB  - The ability to understand and predict the effects of ocean warming (under
      realistic scenarios) on marine biota is of paramount importance, especially at
      the most vulnerable early life stages. Here we investigated the impact of
      predicted environmental warming (+3  degrees C) on the development, metabolism,
      heat shock response and antioxidant defense mechanisms of the early stages of the
      common octopus, Octopus vulgaris. As expected, warming shortened embryonic
      developmental time by 13 days, from 38 days at 18  degrees C to 25 days at 21 
      degrees C. Concomitantly, survival decreased significantly (~29.9 %). Size at
      hatching varied inversely with temperature, and the percentage of smaller
      premature paralarvae increased drastically, from 0 % at 18  degrees C to 17.8 %
      at 21  degrees C. The metabolic costs of the transition from an encapsulated
      embryo to a free planktonic form increased significantly with warming, and HSP70
      concentrations and glutathione S-transferase activity levels were significantly
      magnified from late embryonic to paralarval stages. Yet, despite the presence of
      effective antioxidant defense mechanisms, ocean warming led to an augmentation of
      malondialdehyde levels (an indicative of enhanced ROS action), a process
      considered to be one of the most frequent cellular injury mechanisms. Thus, the
      present study provides clues about how the magnitude and rate of ocean warming
      will challenge the buffering capacities of octopus embryos and hatchlings'
      physiology. The prediction and understanding of the biochemical and physiological
      responses to warmer temperatures (under realistic scenarios) is crucial for the
      management of highly commercial and ecologically important species, such as O.
      vulgaris.

PMID- 24100468
TI  - Mesogen polarity effects on biaxial nematics. Centrally located dipoles.
AB  - We investigate the phase organisation of thermotropic biaxial Gay-Berne (GB)
      mesogens yielding a biaxial nematic (Nb) phase upon endowing them with a central
      point dipole. We study the effects of changing the strength and orientation of
      the dipole on the phase behaviour, and in particular we examine, using molecular
      dynamics (MD) simulations, the possibility of improving the stability of the Nb
      phase. After mapping the boundaries of the Nb phase, we find that the strength of
      the embedded dipole is the parameter with the strongest influence on the
      mesogenic properties, while its orientation plays a minor role. For these central
      dipole systems, we find that the Nb phase organisation is stable only for
      mesogens with relatively weak dipole moments, while it disappears if
      electrostatic interactions become comparable in magnitude with dispersion
      interactions. 

PMID- 24100470
TI  - Posttraumatic stress following pediatric injury: update on diagnosis, risk
      factors, and intervention.
AB  - After pediatric injury, transient traumatic stress reactions are common, and
      about 1 in 6 children and their parents develop persistent posttraumatic stress
      (PTS) symptoms that are linked to poorer physical and functional recovery. Meta
      analytic studies identify risk factors for persistent PTS, including preinjury
      psychological problems, peritrauma fear and perceived life threat, and posttrauma
      factors such as low social support, maladaptive coping strategies, and parent PTS
      symptoms. There is growing prospective data indicating that children's subjective
      appraisals of the injury and its aftermath influence PTS development. Secondary
      prevention of injury-related PTS often involves parents and focuses on promoting
      adaptive child appraisals and coping strategies. Web-based psychoeducation and
      targeted brief early intervention for injured children and their parents have
      shown a modest effect, but additional research is needed to refine preventive
      approaches. There is a strong evidence base for effective psychological treatment
      of severe and persistent PTS via trauma-focused cognitive behavioral therapy;
      evidence is lacking for psychopharmacological treatment. Pediatric clinicians
      play a key role in preventing injury-related PTS by providing "trauma-informed"
      pediatric care (ie, recognizing preexisting trauma, addressing acute traumatic
      stress reactions associated with the injury event, minimizing potentially
      traumatic aspects of treatment, and identifying children who need additional
      monitoring or referral). 

PMID- 24100469
TI  - Potent antitumor activity of the novel HSP90 inhibitors AUY922 and HSP990 in
      neuroendocrine carcinoid cells.
AB  - The heat shock protein (HSP) 90 chaperone machine involved in numerous oncogenic
      signaling pathways is overexpressed in cancer cells and is currently being
      evaluated for anticancer therapy. Neuroendocrine tumors (NETs) of the
      gastroenteropancreatic (GEP) system comprise a heterogeneous group of tumors with
      increasing incidence and poor prognosis. Here, we report the antiproliferative
      effects of the HSP90 inhibitors AUY922 and HSP990 in neuroendocrine tumor cells.
      Treatment of human pancreatic BON1, bronchopulmonary NCI-H727 and midgut
      carcinoid GOT1 neuroendocrine tumor cells with increasing concentrations of
      AUY922 and HSP990 dose-dependently suppressed cell viability. Significant effects
      on neuroendocrine cell viability were observed with inhibitor concentrations as
      low as 5 nM. Inhibition of cell viability was associated with the induction of
      apoptosis as demonstrated by an increase in sub-G1 events and PARP cleavage.
      HSP90 inhibition was associated with decreased neuroendocrine ErbB and IGF-I
      receptor expression, decreased Erk and Akt phospho-rylation and the induction of
      HSP70 expression. These findings provide evidence that targeted inhibition of
      upregulated HSP90 activity could be useful for the treatment of aggressive
      neuroendocrine tumors resistant to conventional therapy.

PMID- 24100471
TI  - Effects of vercirnon on the activity of CYP3A4, CYP2C19 and CYP2C8 enzymes and
      BCRP and OATP1B1 transporters using probe substrates.
AB  - PURPOSE: Vercirnon is a CCR9 chemokine receptor antagonist being developed for
      the treatment of Crohn's disease. As a variety of concomitant medications are
      often required for the treatment of Crohn's disease, it is important to
      characterise the drug interaction profile of vercirnon. To confirm the results of
      previous in vitro inhibition studies, this study assessed the in vivo effect of
      vercirnon on the activity of cytochrome P450 enzymes (CYP3A4, CYP2C19 and CYP2C8)
      and drug transport proteins (BCRP and OATP1B1) using probe substrates. METHODS:
      This was an open-label, single-sequence, repeat-dose study conducted in 24
      healthy adult subjects. On days 1-4, subjects received probe substrates
      (midazolam, pioglitazone, omeprazole and rosuvastatin; in that order), followed
      by administration of vercirnon 500 mg twice daily (BID) on days 5-14. On days 11
      14, in addition to vercirnon 500 mg BID, subjects also received probe substrates
      as on days 1-4. Blood samples were collected for pharmacokinetic analysis of
      probe substrates, vercirnon and two of its metabolites. RESULTS: Geometric least
      squares mean ratios (90 % confidence interval) of area under the concentration
      time curve from time zero to infinity for probe administered with vercirnon
      (test) compared with probe alone (reference) for midazolam, pioglitazone,
      omeprazole and rosuvastatin were 0.92 (0.85, 0.99), 1.01 (0.95, 1.07), 0.99
      (0.76,1.31) and 0.98 (0.88, 1.09), respectively. CONCLUSIONS: Co-administration
      of probe substrates midazolam, pioglitazone, omeprazole, and rosuvastatin
      following repeat dosing of vercirnon 500 mg BID demonstrated vercirnon had no
      clinically significant effect on CYP3A4, CYP2C8, CYP2C19 enzyme activity or BCRP
      or OATP1B1 transporter activity.

PMID- 24100473
TI  - The expression of HCV-associated host factors is dependent on the hepatoma cell
      line used in HCV studies.
AB  - Chronic infection by hepatitis C virus (HCV) is a major cause of liver cirrhosis
      and hepatocellular carcinoma. At present, the most commonly used in vitro model
      of HCV infection is based on hepatoma cell lines. However, they were obtained
      from different patients and different cancers and/or differ in their
      characteristics and permissiveness to HCV. HCV infection can be modulated by
      several host factors, so we compared six different hepatoma cell lines that are
      used as in vitro models for HCV for some of these host factors: the seven known
      HCV entry factors, the six best-characterized HCV-associated microRNAs, and the
      two single-nucleotide polymorphisms near the IL28B gene associated with response
      to pegylated alpha interferon and ribavirin combination therapy, all assessed by
      quantitative PCR. We showed that the cell lines, including Huh-7 and Huh-7
      derived cells, have different microRNA and HCV entry factor expression profiles
      as well as different IL28B genotypes. In conclusion, some of the observed
      differences might explain the differences in permissiveness of the cell lines,
      but, above all, they raise questions about the reliability of in vitro HCV
      research data gathered to date. 

PMID- 24100472
TI  - A novel model of surgical injury in adult rat kidney: a "pouch model".
AB  - Regenerative mechanisms after surgical injury have been studied in many organs
      but not in the kidney. Studying surgical injury may provide new insights into
      mechanisms of kidney regeneration. In rodent models, extrarenal tissues adhere to
      surgical kidney wound and interfere with healing. We hypothesized that this can
      be prevented by wrapping injured kidney in a plastic pouch. Adult rats tolerated
      5/6 nephrectomy with pouch application well. Histological analysis demonstrates
      that application of the pouch effectively prevented formation of adhesions and
      induced characteristic wound healing manifested by formation of granulation
      tissue. Additionally, selected tubules of the wounded kidney extended into the
      granulation tissue forming branching tubular epithelial outgrowths (TEOs) without
      terminal differentiation. Tubular regeneration outside of renal parenchyma was
      not previously observed, and suggests previously unrecognized capacity for
      regeneration. Our model provides a novel approach to study kidney wound healing. 

PMID- 24100474
TI  - First description of hemagglutination by a virus belonging to the family
      Dicistroviridae.
AB  - Triatoma virus is the only virus whose genome has been sequenced and studied in
      triatomines. It belongs to the family Dicistroviridae. In order to detect whether
      TrV has the ability to agglutinate erythrocytes of domestic and laboratory
      animals, we performed a hemagglutination assay. Positive hemagglutination was
      found for red blood cells of guinea pigs. The HA assay could be used as a
      titration method, at least for purified viral particles obtained from triatomine
      stool. This is the first record of hemagglutinating properties for
      Dicistroviridae. 

PMID- 24100475
TI  - Generation and application of monoclonal antibodies against Rift Valley fever
      virus nucleocapsid protein NP and glycoproteins Gn and Gc.
AB  - Rift Valley fever virus (RVFV) is a vector-borne virus that causes high neonatal
      mortality in livestock and deadly haemorrhagic fever in humans. In this paper, we
      describe the generation of monoclonal antibodies (mabs) against all three
      structural proteins of RVFV (glycoproteins Gn and Gc and nucleocapsid protein
      NP). After immunization of BALB/c mice with individual recombinant proteins, a
      total of 45 clones secreting ELISA-reactive monoclonal antibodies against NP, Gn
      and Gc epitopes were obtained. Twelve clones were directed to NP, 28 to Gn, and 5
      to Gc. Western blot analysis revealed that most of the mabs were reactive to
      linearized epitopes on recombinant as well as native virus proteins. Six mabs
      against NP, 21 against Gn and all mabs against Gc also detected conformational
      epitopes, as shown by indirect immunofluorescence on RVFV-infected cells. All of
      the mabs were evaluated for their use in a competition enzyme-linked
      immunosorbent assay (ELISA) for the detection of a RVFV infection. Several mabs
      were identified that competed with polyclonal rabbit serum, and one of them - mab
      Gn123, raised against Gn protein - was selected for a proof-of-principle study
      with field sera from a recent Rift Valley fever outbreak. The novel Gn-based
      competition ELISA demonstrated high performance, offering a promising alternative
      and addition to serological assays based on nucleocapsid protein. 

PMID- 24100476
TI  - Increase in myopia prevalence in clinic-based populations across a century.
AB  - PURPOSE: The study's aim was to report prevalence estimates and age-related
      trends in refractive error in a clinic-based series and compare them to results
      from studies of a similar nature conducted since 1892. METHODS: Refractive error,
      patient age, and sex were collected from the files of all patients seen at the
      University of Waterloo School of Optometry and Vision Science clinic between
      January 2007 and January 2008. Patients were categorized as having myopia (<-0.5D
      mean ocular refraction [MOR]), hyperopia (>0.5D MOR), emmetropia, astigmatism (<
      0.5D), and/or anisometropia (>1.0D difference between eyes). The prevalence of
      all refractive components was determined overall and in 1- and 5-year age groups,
      and then compared to data from older clinic-based studies. Refractive trends over
      time were noted. The prevalence of myopia and hyperopia were compared to older
      studies. RESULTS: The lowest prevalence of myopia was 5% at 0 to 5 years of age,
      after which it increased to 72% at 20 to 30 years of age and then decreased to
      22% in patients older than 70 years. A myopic peak occurred at 24 years of age.
      The prevalence of hyperopia followed opposite trends with a minimum prevalence of
      6% at 25 to 30 years of age. Peaks in emmetropia prevalence were 55% at 5 to 10
      years of age and 37% at 45 to 50 years of age. The prevalence of astigmatism and
      anisometropia increased with age. The Waterloo Eye Study showed a higher
      prevalence of myopia across all ages compared to the older studies with a peak
      prevalence of 72% compared to 21% in the oldest (Herrnheiser) study from 1892.
      CONCLUSIONS: In the last 100 years, there appears to have been a myopic shift in
      clinic-based populations and myopia prevalence appears to follow a predictable
      pattern with age.

PMID- 24100477
TI  - Cone-rod dysfunction is a sign of early-onset high myopia.
AB  - PURPOSE: High myopia (HM) is one of the leading causes of irreversible blindness
      because of its associated complications. Early-onset HM (eoHM) that presents
      before primary school age may be genetically determined, whereas late-onset HM
      (loHM) is affected by genetic and environmental factors. Identification of signs
      that differentiate eoHM from loHM may provide valuable clues toward understanding
      the molecular basis of HM. METHODS: In this study, 42 subjects with HM were
      recruited, including 32 eoHM (onset age, <=5 years) and 10 loHM (onset age, 12.4
      +/- 2.5 years). Clinical data from these two groups were compared, including best
      visual acuity, refraction, axial length, and electroretinography. RESULTS: The
      mean amplitudes of rod b-wave, maximum a-wave, maximum b-wave, cone a-wave, and
      cone b-wave of patients with eoHM were 179 +/- 72 MUv, -158 +/- 63 MUv, 345 +/-
      105 MUv, -20 +/- 11 MUv, and 42 +/- 21 MUv, respectively, whereas those of
      patients with loHM were 252 +/- 77 MUv, -235 +/- 60 MUv, 464 +/- 65 MUv, -36 +/-
      9 MUv, and 104 +/- 26 MUv, respectively (p < 0.001). Patients with eoHM had
      significantly reduced responses of cones and rods, especially cones, as compared
      with patients with loHM. The cone-rod responses in patients with loHM were within
      normal range. CONCLUSIONS: The findings suggest that cone-rod dysfunction may be
      a sign for eoHM compared with loHM.

PMID- 24100478
TI  - The Cambridge Anti-myopia Study: variables associated with myopia progression.
AB  - PURPOSE: To identify variables associated with myopia progression and to identify
      any interaction between accommodative function, myopia progression, age, and
      treatment effect in the Cambridge Anti-Myopia Study. METHODS: Contact lenses were
      used to improve static accommodation by altering ocular spherical aberration, and
      vision training was performed to improve dynamic accommodation. One hundred forty
      two subjects, aged 14-21 years, were recruited who had a minimum of -0.75D of
      myopia. Subjects were assigned to contact lens treatment only, vision training
      only, contact lens treatment and vision training, or control group. Spherical
      aberration, lag of accommodation, accommodative convergence/accommodation (AC/A)
      ratio, accommodative facility, ocular biometry, and refractive error were
      measured at regular intervals throughout the 2-year trial. RESULTS: Ninety-five
      subjects completed the 24-month trial period. There was no significant difference
      in myopia progression between the four treatment groups at 24 months. Age, lag of
      accommodation, and AC/A ratio were significantly associated with myopia
      progression. There was a significant treatment effect at 12 months in the contact
      lens treatment group in younger subjects, based on a median split, aged under
      16.9 years (p = 0.005). This treatment effect was not maintained over the second
      year of the trial. Younger subjects experienced a greater reduction in lag of
      accommodation with the treatment contact lens at 3 months (p = 0.03), compared to
      older contact lens treatment and control groups. There was no interaction between
      AC/A ratio and contact lens treatment effect. CONCLUSIONS: Age, lag of
      accommodation, and AC/A ratio were significantly associated with myopia
      progression. Although there was no significant treatment effect at 24 months, an
      interaction between age and contact lens treatment suggests younger subjects may
      be more amenable, at least in the short term, to alteration of the visual system
      using optical treatments.

PMID- 24100479
TI  - Ciliary muscle thickness in anisometropia.
AB  - PURPOSE: The purpose of this study was to investigate the relationships between
      ciliary muscle thickness (CMT), refractive error, and axial length both across
      subjects and between the more and less myopic eyes of adults with anisometropia.
      METHODS: Both eyes of 29 adult subjects with at least 1.00 D of anisometropia
      were measured. Ciliary muscle thickness was measured at the maximum thickness
      (CMTMAX) and at 1.0 (CMT1), 2.0 (CMT2), and 3.0 mm (CMT3) posterior to the
      scleral spur, and also at the apical region (Apical CMTMAX = CMTMAX - CMT2, and
      Apical CMT1 = CMT1 - CMT2). Multilevel regression models were used to determine
      the relationship between the various CMT measures and cycloplegic refractive
      error or axial length, and to assess whether there are CMT differences between
      the more and less myopic eyes of an anisometropic adult. RESULTS: CMTMAX, CMT1,
      CMT2, and CMT3 were negatively associated with mean refractive error (all p <=
      0.03), and the strongest association was in the posterior region (CMT2 and CMT3).
      Apical CMTMAX and Apical CMT1, however, were positively associated with mean
      refractive error (both p < 0.0001) across subjects. Within a subject, i.e.,
      comparing the two anisometropic eyes, there was no statistically significant
      difference in CMT in any region. CONCLUSIONS: Similar to previous studies, across
      anisometropic subjects, a thicker posterior region of the ciliary muscle (CMT2
      and CMT3) was associated with increased myopic refractive error. Conversely,
      shorter, more hyperopic eyes tended to have thicker anterior, apical fiber
      portions of their ciliary muscle (Apical CMTMAX and Apical CMT1). There was no
      difference between the two eyes for any CMT measurement, indicating that in
      anisometropia, an eye can grow longer and more myopic than its fellow eye without
      resulting in an increase in CMT.

PMID- 24100480
TI  - Astigmatism and myopia in Tohono O'odham Native American children.
AB  - PURPOSE: To describe change in spherical equivalent (M) in a longitudinal sample
      of Tohono O'odham students ages 3 to 18 years and to test the hypothesis that
      astigmatism creates complex cues to emmetropization, resulting in increased
      change in M in the direction of increasing myopia and increased occurrence of
      myopia. METHODS: Subjects were 777 Tohono O'odham Native American children on
      whom cycloplegic right eye autorefraction was measured on at least two study
      encounters between ages 3 and 18 years (first encounter prior to age 5.5 years,
      final encounter >=3 years later). Regression lines were fit to individual
      subjects' longitudinal M data to estimate rate of change in M (regression slope,
      D/yr). Regression was also used to predict if a subject would be myopic (<=-0.75
      D M) by age 18 years. Analysis of covariance was used to assess the relation
      between M slope and magnitude of baseline M and astigmatism. Chi-square analyses
      were used to assess the relation between predicted myopia onset and magnitude of
      baseline M and astigmatism. RESULTS: Mean M slope was significantly more negative
      for hyperopes (M >= +2.00) than for myopes (M <= -0.75) or for subjects neither
      hyperopic nor myopic (NHM, M > -0.75 and < +2.00), but there was no significant
      difference between the myopic and NHM groups. Chi-square analysis indicated that
      final myopia status varied across level of baseline astigmatism. Subjects with
      high astigmatism were more likely to be predicted to have significant myopia by
      age 18 years. CONCLUSIONS: The association between greater shift in M towards
      myopia with age in subjects who were hyperopic at baseline is consistent with
      continued emmetropization in the school years. Results regarding predicted myopia
      development imply that degradation of image quality due to refractive astigmatism
      creates complex cues to emmetropization, resulting in increased occurrence of
      myopia.

PMID- 24100483
TI  - Progression of Fabry cardiomyopathy despite enzyme replacement therapy.

PMID- 24100481
TI  - Coronary artery revascularization in patients with diabetes mellitus.

PMID- 24100484
TI  - Acquired Fontan physiology secondary to acute mechanical tricuspid valve failure
      in a patient with massive right heart enlargement and Ebstein's anomaly.

PMID- 24100486
TI  - Letter by Ammirati and Maseri regarding article, "Bacterial signatures in
      thrombus aspirates of patients with myocardial infarction".

PMID- 24100487
TI  - Letter by Gavriilaki et al regarding article, "Bacterial signatures in thrombus
      aspirates of patients with myocardial infarction".

PMID- 24100488
TI  - Response to letters regarding article, "Bacterial signatures in thrombus
      aspirates of patients with myocardial infarction".

PMID- 24100489
TI  - Plasmodium falciparum Polymorphisms associated with ex vivo drug susceptibility
      and clinical effectiveness of artemisinin-based combination therapies in Benin.
AB  - Artemisinin-based combination therapies (ACTs) are the main option to treat
      malaria, and their efficacy and susceptibility must be closely monitored to avoid
      resistance. We assessed the association of Plasmodium falciparum polymorphisms
      and ex vivo drug susceptibility with clinical effectiveness. Patients enrolled in
      an effectiveness trial comparing artemether-lumefantrine (n = 96), fixed-dose
      artesunate-amodiaquine (n = 96), and sulfadoxine-pyrimethamine (n = 48) for the
      treatment of uncomplicated malaria 2007 in Benin were assessed. pfcrt, pfmdr1,
      pfmrp1, pfdhfr, and pfdhps polymorphisms were analyzed pretreatment and in
      recurrent infections. Drug susceptibility was determined in fresh baseline
      isolates by Plasmodium lactate dehydrogenase enzyme-linked immunosorbent assay
      (ELISA). A majority had 50% inhibitory concentration (IC50) estimates (the
      concentration required for 50% growth inhibition) lower than those of the 3D7
      reference clone for desethylamodiaquine, lumefantrine, mefloquine, and quinine
      and was considered to be susceptible, while dihydroartemisinin and pyrimethamine
      IC50s were higher. No association was found between susceptibility to the ACT
      compounds and treatment outcome. Selection was observed for the pfmdr1 N86 allele
      in artemether-lumefantrine recrudescences (recurring infections) (4/7 [57.1%]
      versus 36/195 [18.5%]), and of the opposite allele, 86Y, in artesunate
      amodiaquine reinfections (new infections) (20/22 [90.9%] versus 137/195 [70.3%])
      compared to baseline infections. The importance of pfmdr1 N86 in lumefantrine
      tolerance was emphasized by its association with elevated lumefantrine IC50s.
      Genetic linkage between N86 and Y184 was observed, which together with the low
      frequency of 1246Y may explain regional differences in selection of pfmdr1 loci.
      Selection of opposite alleles in artemether-lumefantrine and artesunate
      amodiaquine recurrent infections supports the strategy of multiple first-line
      treatment. Surveillance based on clinical, ex vivo, molecular, and
      pharmacological data is warranted. 

PMID- 24100490
TI  - Evaluation of the efficacies of Amphotericin B, Posaconazole, Voriconazole, and
      Anidulafungin in a murine disseminated infection by the emerging opportunistic
      Fungus Sarocladium (Acremonium) kiliense.
AB  - We evaluated and compared the efficacies of different antifungal drugs against
      Sarocladium kiliense (formerly Acremonium kiliense), a clinically relevant
      opportunistic fungus, in a murine model of systemic infection. Three clinical
      strains of this fungus were tested, and the therapy administered was as follows:
      posaconazole at 20 mg/kg of body weight (twice daily), voriconazole at 40 mg/kg,
      anidulafungin at 10 mg/kg, or amphotericin B at 0.8 mg/kg. The efficacy was
      evaluated by prolonged animal survival, tissue burden reduction, and (1->3)-beta
      d-glucan serum levels. In general, the four antifungal drugs showed high MICs and
      poor in vitro activity. The efficacy of the different treatments was only modest,
      since survival rates were never higher than 40% and no drug was able to reduce
      fungal load in all the organs for the three strains tested. Posaconazole, in
      spite of its high MICs (>=16 MUg/ml), showed the highest efficacy. The (1->3)
      beta-d-glucan serum levels were equally reduced by all drugs evaluated. 

PMID- 24100491
TI  - In vitro activities of eight antifungal drugs against 106 waterborne and
      cutaneous exophiala species.
AB  - The in vitro activities of eight antifungal drugs against 106 clinical and
      environmental isolates of waterborne and cutaneous Exophiala species were tested.
      The MICs and minimum effective concentrations for 90% of the strains tested (n =
      106) were, in increasing order, as follows: posaconazole, 0.063 MUg/ml;
      itraconazole, 0.25 MUg/ml; micafungin, 1 MUg/ml; voriconazole, 2 MUg/ml;
      isavuconazole, 4 MUg/ml; caspofungin, 8 MUg/ml; amphotericin B, 16 MUg/ml;
      fluconazole, 64 MUg/ml. 

PMID- 24100492
TI  - Epidemiology of bloodstream infections caused by Acinetobacter baumannii and
      impact of drug resistance to both carbapenems and ampicillin-sulbactam on
      clinical outcomes.
AB  - Acinetobacter baumannii has become a leading cause of bloodstream infections
      (BSI) in health care settings. Although the incidence of infection with
      carbapenem- and ampicillin-sulbactam-resistant (CASR) A. baumannii has increased,
      there is a scarcity of studies which investigate BSI caused by CASR A. baumannii.
      A retrospective cohort study was conducted on adult patients with BSI caused by
      A. baumannii and who were admitted to the Detroit Medical Center between January
      2006 and April 2009. Medical records were queried for patients' demographics,
      antimicrobial exposures, comorbidities, hospital stay, and clinical outcomes.
      Bivariate analyses and logistic regression were employed in the study. Two
      hundred seventy-four patients with BSI caused by A. baumannii were included in
      the study: 68 (25%) caused by CASR A. baumannii and 206 (75%) caused by non-CASR
      A. baumannii. In multivariate analysis, factors associated with BSI caused by
      CASR A. baumannii included admission with a rapidly fatal condition (odds ratio
      [OR] = 2.83, 95% confidence interval [CI] = 1.27 to 6.32, P value = 0.01) and
      prior use of antimicrobials (OR = 2.83, 95% CI = 1.18 to 6.78, P value = 0.02).
      In-hospital mortality rates for BSI caused by CASR A. baumannii were
      significantly higher than those for non-CASR A. baumannii-induced BSI (43% versus
      20%; OR = 3.0, 95% CI = 1.60 to 5.23, P value < 0.001). However, after adjusting
      for potential confounders, the association between BSI caused by CASR A.
      baumannii and increased risk of in-hospital mortality was not significant (OR =
      1.15, 95% CI = 0.51 to 2.63, P value = 0.74). This study demonstrated that CASR
      A. baumannii had a distinct epidemiology compared to more susceptible A.
      baumannii strains; however, clinical outcomes were similar for the two groups.
      Admission with a rapidly fatal condition was an independent predictor for both
      CASR A. baumannii and in-hospital mortality. 

PMID- 24100493
TI  - Effects of substitutions at the 4' and 2 positions on the bioactivity of 4'
      ethynyl-2-fluoro-2'-deoxyadenosine.
AB  - Nucleos(t)ide reverse transcriptase inhibitors (NRTIs) form the backbone of most
      anti-HIV therapies. We have shown that 4'-ethynyl-2-fluoro-2'-deoxyadenosine
      (EFdA) is a highly effective NRTI; however, the reasons for the potent antiviral
      activity of EFdA are not well understood. Here, we use a combination of
      structural, computational, and biochemical approaches to examine how
      substitutions in the sugar or adenine rings affect the incorporation of dA-based
      NRTIs like EFdA into DNA by HIV RT and their susceptibility to deamination by
      adenosine deaminase (ADA). Nuclear magnetic resonance (NMR) spectroscopy studies
      of 4'-substituted NRTIs show that ethynyl or cyano groups stabilize the sugar
      ring in the C-2'-exo/C-3'-endo (north) conformation. Steady-state kinetic
      analysis of the incorporation of 4'-substituted NRTIs by RT reveals a correlation
      between the north conformation of the NRTI sugar ring and efficiency of
      incorporation into the nascent DNA strand. Structural analysis and the kinetics
      of deamination by ADA demonstrate that 4'-ethynyl and cyano substitutions
      decrease the susceptibility of adenosine-based compounds to ADA through steric
      interactions at the active site. However, the major determinant for decreased
      susceptibility to ADA is the 2-halo substitution, which alters the pKa of N1 on
      the adenine base. These results provide insight into how NRTI structural
      attributes affect their antiviral activities through their interactions with the
      RT and ADA active sites. 

PMID- 24100494
TI  - Efficacy of tecovirimat (ST-246) in nonhuman primates infected with variola virus
      (Smallpox).
AB  - Naturally occurring smallpox has been eradicated but remains a considerable
      threat as a biowarfare/bioterrorist weapon (F. Fleck, Bull. World Health Organ.
      81:917-918, 2003). While effective, the smallpox vaccine is currently not
      recommended for routine use in the general public due to safety concerns
      (http://www.bt.cdc.gov/agent/smallpox/vaccination). Safe and effective
      countermeasures, particularly those effective after exposure to smallpox, are
      needed. Currently, SIGA Technologies is developing the small-molecule oral drug,
      tecovirimat (previously known as ST-246), as a postexposure therapeutic treatment
      of orthopoxvirus disease, including smallpox. Tecovirimat has been shown to be
      efficacious in preventing lethal orthopoxviral disease in numerous animal models
      (G. Yang, D. C. Pevear, M. H. Davies, M. S. Collett, T. Bailey, et al., J. Virol.
      79:13139-13149, 2005; D. C. Quenelle, R. M. Buller, S. Parker, K. A. Keith, D. E.
      Hruby, et al., Antimicrob. Agents Chemother., 51:689-695, 2007; E. Sbrana, R.
      Jordan, D. E. Hruby, R. I. Mateo, S. Y. Xiao, et al., Am. J. Trop. Med. Hyg.
      76:768-773, 2007). Furthermore, in clinical trials thus far, the drug appears to
      be safe, with a good pharmacokinetic profile. In this study, the efficacy of
      tecovirimat was evaluated in both a prelesional and postlesional setting in
      nonhuman primates challenged intravenously with 1 * 10(8) PFU of Variola virus
      (VARV; the causative agent of smallpox), a model for smallpox disease in humans.
      Following challenge, 50% of placebo-treated controls succumbed to infection,
      while all tecovirimat-treated animals survived regardless of whether treatment
      was started at 2 or 4 days postinfection. In addition, tecovirimat treatment
      resulted in dramatic reductions in dermal lesion counts, oropharyngeal virus
      shedding, and viral DNA circulating in the blood. Although clinical disease was
      evident in tecovirimat-treated animals, it was generally very mild and appeared
      to resolve earlier than in placebo-treated controls that survived infection.
      Tecovirimat appears to be an effective smallpox therapeutic in nonhuman primates,
      suggesting that it is reasonably likely to provide therapeutic benefit in
      smallpox-infected humans. 

PMID- 24100495
TI  - In vitro phenotypic characterization of hepatitis C virus NS3 protease variants
      observed in clinical studies of telaprevir.
AB  - Telaprevir is a linear, peptidomimetic small molecule that inhibits hepatitis C
      virus (HCV) replication by specifically inhibiting the NS3.4A protease. In phase
      3 clinical studies, telaprevir in combination with peginterferon and ribavirin
      (PR) significantly improved sustained virologic response (SVR) rates in genotype
      1 chronic HCV-infected patients compared with PR alone. In patients who do not
      achieve SVR after treatment with telaprevir-based regimens, variants with
      mutations in the NS3.4A protease region have been observed. Such variants can
      contribute to drug resistance and limit the efficacy of treatment. To gain a
      better understanding of the viral resistance profile, we conducted phenotypic
      characterization of the variants using HCV replicons carrying site-directed
      mutations. The most frequently observed (significantly enriched) telaprevir
      resistant variants, V36A/M, T54A/S, R155K/T, and A156S, conferred lower-level
      resistance (3- to 25-fold), whereas A156T and V36M+R155K conferred higher-level
      resistance (>25-fold) to telaprevir. Rarely observed (not significantly enriched)
      variants included V36I/L and I132V, which did not confer resistance to
      telaprevir; V36C/G, R155G/I/M/S, V36A+T54A, V36L+R155K, T54S+R155K, and
      R155T+D168N, which conferred lower-level resistance to telaprevir; and A156F/N/V,
      V36A+R155K/T, V36M+R155T, V36A/M+A156T, T54A+A156S, T54S+A156S/T, and
      V36M+T54S+R155K, which conferred higher-level resistance to telaprevir. All
      telaprevir-resistant variants remained fully sensitive to alpha interferon,
      ribavirin, and HCV NS5B nucleoside and nonnucleoside polymerase inhibitors. In
      general, the replication capacity of telaprevir-resistant variants was lower than
      that of the wild-type replicon. 

PMID- 24100496
TI  - In vitro characterization of PlySK1249, a novel phage lysin, and assessment of
      its antibacterial activity in a mouse model of Streptococcus agalactiae
      bacteremia.
AB  - Beta-hemolytic Streptococcus agalactiae is the leading cause of bacteremia and
      invasive infections. These diseases are treated with beta-lactams or macrolides,
      but the emergence of less susceptible and even fully resistant strains is a cause
      for concern. New bacteriophage lysins could be promising alternatives against
      such organisms. They hydrolyze the bacterial peptidoglycan at the end of the
      phage cycle, in order to release the phage progeny. By using a bioinformatic
      approach to screen several beta-hemolytic streptococci, a gene coding for a lysin
      was identified on a prophage carried by Streptococcus dysgalactiae subsp.
      equisimilis SK1249. The gene product, named PlySK1249, harbored an original three
      domain structure with a central cell wall-binding domain surrounded by an N
      terminal amidase and a C-terminal CHAP domain. Purified PlySK1249 was highly
      lytic and bactericidal for S. dysgalactiae (2-log10 CFU/ml decrease within 15
      min). Moreover, it also efficiently killed S. agalactiae (1.5-log10 CFU/ml
      decrease within 15 min) but not several streptococcal commensal species. We
      further investigated the activity of PlySK1249 in a mouse model of S. agalactiae
      bacteremia. Eighty percent of the animals (n = 10) challenged intraperitoneally
      with 10(6) CFU of S. agalactiae died within 72 h, whereas repeated injections of
      PlySK1249 (45 mg/kg 3 times within 24 h) significantly protected the mice (P <
      0.01). Thus, PlySK1249, which was isolated from S. dysgalactiae, demonstrated
      high cross-lytic activity against S. agalactiae both in vitro and in vivo. These
      encouraging results indicated that PlySK1249 might represent a good candidate to
      be developed as a new enzybiotic for the treatment of systemic S. agalactiae
      infections. 

PMID- 24100497
TI  - Sensititre MYCOTB MIC plate for testing Mycobacterium tuberculosis susceptibility
      to first- and second-line drugs.
AB  - For Mycobacterium tuberculosis, phenotypic methods for drug susceptibility
      testing of second-line drugs are poorly standardized and technically challenging.
      The Sensititre MYCOTB MIC plate (MYCOTB) is a microtiter plate containing
      lyophilized antibiotics and configured for determination of MICs to first- and
      second-line antituberculosis drugs. To evaluate the performance of MYCOTB for M.
      tuberculosis drug susceptibility testing using the Middlebrook 7H10 agar
      proportion method (APM) as the comparator, we conducted a two-site study using
      archived M. tuberculosis isolates from Uganda and the Republic of Korea. Thawed
      isolates were subcultured, and dilutions were inoculated into MYCOTB wells and
      onto 7H10 agar. MYCOTB results were read at days 7, 10, 14, and 21; APM results
      were read at 21 days. A total of 222 isolates provided results on both platforms.
      By APM, 106/222 (47.7%) of isolates were resistant to at least isoniazid and
      rifampin. Agreement between MYCOTB and APM with respect to susceptibility or
      resistance was >=92% for 7 of 12 drugs when a strict definition was used and
      >=96% for 10 of 12 drugs when agreement was defined by allowing a +/- one-well
      range of dilutions around the APM critical concentration. For ethambutol,
      agreement was 80% to 81%. For moxifloxacin, agreement was 83% to 85%;
      incorporating existing DNA sequencing information for discrepant analysis raised
      agreement to 91% to 96%. For MYCOTB, the median time to plate interpretation was
      10 days and interreader agreement was >=95% for all drugs. MYCOTB provided
      reliable results for M. tuberculosis susceptibility testing of first- and second
      line drugs except ethambutol, and results were available sooner than those
      determined by APM. 

PMID- 24100498
TI  - Differential susceptibilities to azithromycin treatment of chlamydial infection
      in the gastrointestinal tract and cervix.
AB  - Evidence from animal studies suggests that chlamydiae may persist in the
      gastrointestinal tract (GI) and be a reservoir for reinfection of the genital
      tract. We hypothesize that there may be a differential susceptibility of
      organisms in the GI and genital tracts. To determine the effect of azithromycin
      on persistent chlamydial gut infection, C57BL/6 and BALB/c mice were infected
      orally and genitally and treated with azithromycin (Az) orally (20, 40, or 80
      mg/kg of body weight), and the numbers of chlamydiae were determined from cervix
      and cecal tissues. The Az concentration in the cecum and cervix was measured by
      high-performance liquid chromatography with electrochemical detection (HPLC-ECD).
      Az treatment cleared genital infection in both C57BL/6 and BALB/c mice; however,
      GI infection was not cleared with the same doses. HPLC data showed the presence
      of Az at both sites of infection, and significant amounts of Az were measured in
      treatment groups. However, no significant difference in Az levels between the
      cecum and the cervix was observed, indicating similar levels of Az reaching both
      sites of infection. These data indicate that antibiotic levels that are
      sufficient to cure genital infection are ineffectual against GI infection. The
      results suggest a reevaluation of antibiotic therapy for chlamydial infection. 

PMID- 24100499
TI  - Antimicrobial activity of ceftolozane-tazobactam tested against
      Enterobacteriaceae and Pseudomonas aeruginosa with various resistance patterns
      isolated in U.S. Hospitals (2011-2012).
AB  - Ceftolozane/tazobactam, a novel antimicrobial agent with activity against
      Pseudomonas aeruginosa (including drug-resistant strains) and other common Gram
      negative pathogens (including most extended-spectrum-beta-lactamase [ESBL]
      producing Enterobacteriaceae strains), and comparator agents were susceptibility
      tested by a reference broth microdilution method against 7,071 Enterobacteriaceae
      and 1,971 P. aeruginosa isolates. Isolates were collected consecutively from
      patients in 32 medical centers across the United States during 2011 to 2012.
      Overall, 15.7% and 8.9% of P. aeruginosa isolates were classified as multidrug
      resistant (MDR) and extensively drug resistant (XDR), and 8.4% and 1.2% of
      Enterobacteriaceae were classified as MDR and XDR. No pandrug-resistant (PDR)
      Enterobacteriaceae isolates and only one PDR P. aeruginosa isolate were detected.
      Ceftolozane/tazobactam was the most potent (MIC50/90, 0.5/2 MUg/ml) agent tested
      against P. aeruginosa and demonstrated good activity against 310 MDR strains
      (MIC50/90, 2/8 MUg/ml) and 175 XDR strains (MIC50/90, 4/16 MUg/ml).
      Ceftolozane/tazobactam exhibited high overall activity (MIC50/90, 0.25/1 MUg/ml)
      against Enterobacteriaceae and retained activity (MIC50/90, 4/>32 MUg/ml) against
      many 601 MDR strains but not against the 86 XDR strains (MIC50, >32 MUg/ml).
      Ceftolozane/tazobactam was highly potent (MIC50/90, 0.25/0.5 MUg/ml) against
      2,691 Escherichia coli isolates and retained good activity against most ESBL
      phenotype E. coli isolates (MIC50/90, 0.5/4 MUg/ml), but activity was low against
      ESBL-phenotype Klebsiella pneumoniae isolates (MIC50/90, 32/>32 MUg/ml),
      explained by the high rate (39.8%) of meropenem coresistance observed in this
      species phenotype. In summary, ceftolozane/tazobactam demonstrated high potency
      and broad-spectrum activity against many contemporary Enterobacteriaceae and P.
      aeruginosa isolates collected in U.S. medical centers. Importantly,
      ceftolozane/tazobactam retained potency against many MDR and XDR strains. 

PMID- 24100500
TI  - Isavuconazole (BAL4815) pharmacodynamic target determination in an in vivo murine
      model of invasive pulmonary aspergillosis against wild-type and cyp51 mutant
      isolates of Aspergillus fumigatus.
AB  - Invasive pulmonary aspergillosis (IPA) continues to rise in concert with
      increasing numbers of immune suppression techniques to treat other medical
      conditions and transplantation. Despite these advances, morbidity and mortality
      rates remain unacceptably high. One strategy used to optimize outcomes is
      antifungal pharmacodynamic (PD) examination. We explored the pharmacodynamics of
      a new triazole in development, isavuconazole, in a murine neutropenic IPA model.
      Ten A. fumigatus isolates were used, including four wild-type isolates and six
      cyp51 mutants. The MIC range was 0.125 to 8 mg/liter. Following infection, groups
      of mice were treated orally with the prodrug (BAL8557) at 40 to 640 mg/kg/12 h
      for 7 days. Efficacy was determined by quantitative PCR of lung homogenates. At
      the start of therapy, mice had 4.97 log10 conidial equivalents (CE)/ml of lung
      homogenate, and this increased to 6.82 log10 CE/ml of lung homogenate in
      untreated animals. The infection model was uniformly lethal in untreated control
      mice. The PD target endpoints examined included the static-dose AUC/MIC ratio and
      the 1-log10 killing AUC/MIC ratio. A stasis endpoint was achieved for all
      isolates with an MIC of <=1 mg/liter and 1-log10 killing in all isolates with an
      MIC of <=0.5 mg/liter, regardless of the presence or absence of the cyp51
      mutation. The static-dose range was 65 to 617 mg/kg/12 h. The corresponding
      median free-drug AUC/MIC ratio was near 5. The 1-log10 killing dose range was 147
      to 455 mg/kg/12 h, and the corresponding median free-drug AUC/MIC ratio was 11.1.
      These values are similar to those previously reported for other triazoles. 

PMID- 24100501
TI  - Caprine abscess model of tulathromycin concentrations in interstitial fluid from
      tissue chambers inoculated with Corynebacterium pseudotuberculosis following
      subcutaneous or intrachamber administration.
AB  - Corynebacterium pseudotuberculosis causes chronic, suppurative, abscessing
      conditions in livestock and humans. We used an in vivo model to evaluate
      antimicrobial efficacy for focal abscesses caused by C. pseudotuberculosis.
      Tissue chambers were surgically implanted in the subcutaneous tissues of the
      right and left paralumbar fossa of 12 goats to serve as a model for isolated,
      focal abscesses. For each goat, one tissue chamber was inoculated with C.
      pseudotuberculosis, while the contralateral chamber served as an uninoculated
      control. Six goats were administered a single dose of tulathromycin at 2.5 mg/kg
      of body weight subcutaneously, while the other six received the same dose by
      injection directly into the inoculated chambers. Our objective was to compare the
      effects and tulathromycin concentrations in interstitial fluid (IF) samples
      collected from C. pseudotuberculosis-infected and control chambers following
      subcutaneous or intrachamber injection of tulathromycin. In addition, the effects
      of tulathromycin on the quantity of C. pseudotuberculosis reisolated from
      inoculated chambers were assessed over time. Tulathromycin IF concentrations from
      C. pseudotuberculosis-infected and control tissue chambers were similar to those
      in plasma following subcutaneous administration. Following intrachamber
      administration, tulathromycin IF concentrations in infected chambers were
      continuously above the MIC for the C. pseudotuberculosis isolate for 15 days.
      There were no significant differences for plasma area under the curve and
      elimination half-lives between subcutaneous and intrachamber administration. Six
      of the 12 infected chambers had no growth of C. pseudotuberculosis 15 days
      postadministration. Results of this study indicate that tulathromycin may be
      beneficial in the treatment of focal infections such as those caused by C.
      pseudotuberculosis. 

PMID- 24100502
TI  - A perspective on how the United States fell behind Northern Europe in the battle
      against methicillin-resistant Staphylococcus aureus.

PMID- 24100503
TI  - Functional role of methylation of G518 of the 16S rRNA 530 loop by GidB in
      Mycobacterium tuberculosis.
AB  - Posttranscriptional modifications of bacterial rRNA serve a variety of purposes,
      from stabilizing ribosome structure to preserving its functional integrity. Here,
      we investigated the functional role of one rRNA modification in particular-the
      methylation of guanosine at position 518 (G518) of the 16S rRNA in Mycobacterium
      tuberculosis. Based on previously reported evidence that G518 is located 5 A;
      from proline 44 of ribosomal protein S12, which interacts directly with the mRNA
      wobble position of the codon:anticodon helix at the A site during translation, we
      speculated that methylation of G518 affects protein translation. We transformed
      reporter constructs designed to probe the effect of functional lesions at one of
      the three codon positions on translational fidelity into the wild-type strain,
      H37Rv, and into a DeltagidB mutant, which lacks the methyltransferase (GidB) that
      methylates G518. We show that mistranslation occurs less in the DeltagidB mutant
      only in the construct bearing a lesion in the wobble position compared to H37Rv.
      Thus, the methylation of G518 allows mistranslation to occur at some level in
      order for translation to proceed smoothly and efficiently. We also explored the
      role of methylation at G518 in altering the susceptibility of M. tuberculosis to
      streptomycin (SM). Using high-performance liquid chromatography-tandem mass
      spectrometry (HPLC-MS/MS), we confirmed that G518 is not methylated in the
      DeltagidB mutant. Furthermore, isothermal titration calorimetry experiments
      performed on 70S ribosomes purified from wild-type and DeltagidB mutant strains
      showed that methylation significantly enhances SM binding. These results provide
      a mechanistic explanation for the low-level, SM-resistant phenotype observed in
      M. tuberculosis strains that contain a gidB mutation. 

PMID- 24100504
TI  - Megalin contributes to kidney accumulation and nephrotoxicity of colistin.
AB  - Interest has recently been shown again in colistin because of the increased
      prevalence of infections caused by multidrug-resistant Gram-negative bacteria.
      Although the potential for nephrotoxicity is a major dose-limiting factor in
      colistin use, little is known about the mechanisms that underlie colistin-induced
      nephrotoxicity. In this study, we focused on an endocytosis receptor, megalin,
      that is expressed in renal proximal tubules, with the aim of clarifying the role
      of megalin in the kidney accumulation and nephrotoxicity of colistin. We examined
      the binding of colistin to megalin by using a vesicle assay. The kidney
      accumulation, urinary excretion, and concentrations in plasma of colistin in
      megalin-shedding rats were also evaluated. Furthermore, we examined the effect of
      megalin ligands and a microtubule-depolymerizing agent on colistin-induced
      nephrotoxicity. We found that cytochrome c, a typical megalin ligand, inhibited
      the binding of colistin to megalin competitively. In megalin-shedding rats, renal
      proximal tubule colistin accumulation was decreased (13.5 +/- 1.6 and 21.3 +/-
      2.6 MUg in megalin-shedding and control rats, respectively). Coadministration of
      colistin and cytochrome c or albumin fragments resulted in a significant decrease
      in urinary N-acetyl-beta-d-glucosaminidase (NAG) excretion, a marker of renal
      tubular damage (717.1 +/- 183.9 mU/day for colistin alone, 500.8 +/- 102.4 mU/day
      for cytochrome c with colistin, and 406.7 +/- 156.7 mU/day for albumin fragments
      with colistin). Moreover, coadministration of colistin and colchicine, a
      microtubule-depolymerizing agent, resulted in a significant decrease in urinary
      NAG excretion. In conclusion, our results indicate that colistin acts as a
      megalin ligand and that megalin plays a key role in the accumulation in the
      kidney and nephrotoxicity of colistin. Megalin ligands may be new targets for the
      prevention of colistin-induced nephrotoxicity. 

PMID- 24100505
TI  - Vitamin D and prolonged treatment with photosensitivity-associated antibiotics.

PMID- 24100506
TI  - Efficacy of adefovir-based combination therapy for patients with Lamivudine- and
      entecavir-resistant chronic hepatitis B virus infection.
AB  - Treatment strategies for entecavir (ETV)-resistant chronic hepatitis B (CHB)
      patients are not yet well established. The aim of this study was to evaluate
      overall antiviral efficacy and to compare the efficacy of combination therapy
      with adefovir (ADV) plus nucleoside analogues (lamivudine [LAM], telbivudine
      [LdT], or ETV) in patients infected with LAM- and ETV-resistant hepatitis B virus
      (HBV) variants. Virologic, biochemical, and serologic responses during
      combination therapy with ADV plus nucleoside analogues were assessed. Propensity
      score analysis was used to select a matched group of patients for the comparison
      of rescue therapy regimens. A total of 67 consecutive patients were analyzed.
      Complete virologic suppression was achieved in 27 patients. The overall
      cumulative incidence of complete virologic suppression at month 24 was 47.4%:
      44.3% in the LAM or LdT plus ADV group and 51.4% in the group given ETV and ADV.
      There was no significant difference between these two groups (P = 0.234). The
      cumulative incidences of complete virologic suppression were still comparable
      between the two groups selected and matched using the propensity score model (P =
      0.419). Virologic breakthrough was observed in 9 patients, and rtA181V
      substitution was newly detected in one patient. Hepatitis B e antigen (HBeAg)
      negativity and lower baseline HBV DNA level were associated with complete
      virologic suppression in univariate analysis. In multivariate analysis, lower
      baseline HBV DNA level remained an independent predictor. In conclusion,
      combination therapy with ADV plus nucleoside analogues fails to show sufficient
      antiviral efficacy in CHB patients with resistance to both LAM and ETV. Further
      study is warranted to evaluate the efficacy of a more potent tenofovir-based
      regimen in such patients. 

PMID- 24100508
TI  - Synthesis and magnetothermal properties of a ferromagnetically coupled Ni(II)
      Gd(III)-Ni(II) cluster.
AB  - A linear trimeric cluster of molecular formula [Ni2Gd(L(-))6](NO3) (1) (L(-) =
      (C14H12NO2) has been isolated with its structure determined via single crystal X
      ray diffraction. Magnetic susceptibility measurements of 1 show that the nickel
      and gadolinium ions are coupled ferromagnetically, with a ground total spin state
      (S) of 11/2. Best fit spin Hamiltonian parameters obtained for 1 are J(1(Ni-Gd))
      = +0.54 cm(-1), g = 2.01. EPR measurements confirm a low magnetic anisotropy (D =
      -0.135 cm(-1)) for 1. Heat capacity determination of the magnetocaloric effect
      (MCE) parameters for 1 shows that the change in magnetic entropy (-DeltaS(m))
      achieves a maximum of 13.74 J kg(-1) K(-1) at 4.0 K, with the ferromagnetic
      coupling giving a rapid change in low applied fields, confirming the potential of
      Gd molecular derivatives as coolants at liquid helium temperature.

PMID- 24100507
TI  - MLS-2384, a new 6-bromoindirubin derivative with dual JAK/Src kinase inhibitory
      activity, suppresses growth of diverse cancer cells.
AB  - Janus kinase (JAK) and Src kinase are the two major tyrosine kinase families
      upstream of signal transducer and activator of transcription (STAT). Among the
      seven STAT family proteins, STAT3 is constitutively activated in many diverse
      cancers. Upon activation, JAK and Src kinases phosphorylate STAT3, and thereby
      promote cell growth and survival. MLS-2384 is a novel 6-bromoindirubin derivative
      with a bromo-group at the 6-position on one indole ring and a hydrophilic group
      at the 3'-position on the other indole ring. In this study, we investigated the
      kinase inhibitory activity and anticancer activity of MLS-2384. Our data from in
      vitro kinase assays, cell viability analyses, western blotting analyses, and
      animal model studies, demonstrate that MLS-2384 is a dual JAK/Src kinase
      inhibitor, and suppresses growth of various human cancer cells, such as prostate,
      breast, skin, ovarian, lung, and liver. Consistent with the inactivation of JAK
      and Src kinases, phosphorylation of STAT3 was inhibited in a dose-dependent
      manner in the cancer cells treated with MLS-2384. STAT3 downstream proteins
      involved in cell proliferation and survival, such as c-Myc and Mcl-1, are
      downregulated by MLS-2384 in prostate cancer cells, whereas survivin is
      downregulated in A2058 cells. In these two cancer cell lines, PARP is cleaved,
      indicating that MLS-2384 induces apoptosis in human melanoma and prostate cancer
      cells. Importantly, MLS-2384 suppresses tumor growth with low toxicity in a mouse
      xenograft model of human melanoma. Taken together, MLS-2384 demonstrates dual
      JAK/Src inhibitory activity and suppresses tumor cell growth both in vitro and in
      vivo. Our findings support further development of MLS-2384 as a potential small
      molecule therapeutic agent that targets JAK, Src, and STAT3 signaling in multiple
      human cancer cells. 

PMID- 24100509
TI  - Specific transduction and labeling of pancreatic ducts by targeted recombinant
      viral infusion into mouse pancreatic ducts.
AB  - Specific labeling of pancreatic ducts has proven to be quite difficult. Such
      labeling has been highly sought after because of the power it would confer to
      studies of pancreatic ductal carcinogenesis, as well as studies of the source of
      new insulin-producing beta-cells. Cre-loxp recombination could, in theory,
      lineage-tag pancreatic ducts, but results have been conflicting, mainly due to
      low labeling efficiencies. Here, we achieved a high pancreatic duct labeling
      efficiency using a recombinant adeno-associated virus (rAAV) with a duct-specific
      sox9 promoter infused into the mouse common biliary/pancreatic duct. We saw
      rapid, diffuse duct-specific labeling, with 50 and 89% labeling in the pancreatic
      tail and head region, respectively. This highly specific labeling of ducts should
      greatly enhance our ability to study the role of pancreatic ducts in numerous
      aspects of pancreatic growth, development and function. 

PMID- 24100510
TI  - Psychosocial work characteristics and sleep--a well-known but poorly understood
      association.

PMID- 24100511
TI  - Assessment of breast volume changes during human pregnancy using a three
      dimensional surface assessment technique in the prospective CGATE study.
AB  - Pregnancies and breastfeeding are two important protective factors concerning
      breast cancer risk. Breast volume and breast volume changes might be a breast
      phenotype that could be monitored during pregnancy and breastfeeding without
      ionizing radiation or expensive equipment. The aim of the present study was to
      document changes in breast volume during pregnancy prospectively. In the
      prospective Clinical Gravidity Association Trial and Evaluation programme,
      pregnant women were followed up prospectively from gestational week 12 to birth.
      Three-dimensional breast surface imaging and subsequent volume assessments were
      performed. Factors influencing breast volume at the end of the pregnancy were
      assessed using linear regression models. Breast volumes averaged 420 ml at the
      start of pregnancy and 516 ml at the end of pregnancy. The first, second and
      third quartiles of the volume increase were 41, 95 and 135 ml, respectively.
      Breast size increased on average by 96 ml, regardless of the initial breast
      volume. Breast volume increases during pregnancy, but not all womens' breasts
      respond to pregnancy in the same way. Breast volume changes during pregnancy are
      an interesting phenotype that can be easily assessed in further studies to
      examine breast cancer risk. 

PMID- 24100512
TI  - Endometrial scratching improves IVF pregnancy rate.

PMID- 24100515
TI  - Exercise therapy for sexual dysfunction after prostate cancer.
AB  - Sexual dysfunction is one of the most common, distressing and persistent adverse
      effects of prostate cancer treatment, and has a profound effect on quality of
      life for the patient and his partner. Current health-care provisions are
      inadequate to address the demand for the management of sexual dysfunction, with
      approximately half of prostate cancer survivors reporting unmet sexual health
      care needs. Management strategies predominately involve pharmacological
      interventions to address the direct physiological effects of prostate cancer
      treatment on erectile function. However, the aetiology of sexual dysfunction is
      multifaceted and considerable physiological and psychological adverse effects of
      prostate cancer treatments, which are not addressed by pharmacological
      intervention, contribute to sexual dysfunction. Exercise has established efficacy
      for improving many of these factors in men with prostate cancer, including
      changes in body composition (especially to counteract body feminization),
      fatigue, physical function, risk of comorbid conditions, depression, anxiety and
      quality of life. Emerging evidence indicates that exercise also has a positive
      effect on sexual desire and sexual activity in men with prostate cancer. 

PMID- 24100517
TI  - Robot-assisted laparoscopic urological surgery in children.
AB  - Robot-assisted laparoscopic surgery (RALS) has been proven to be safe and
      effective for various urological procedures in children, including pyeloplasty,
      orchiopexy, nephrectomy, and bladder augmentation. The robot system enables
      delicate and precise movements, which are ideal for the types of reconstructive
      surgeries that children with urological issues often require, overcoming many of
      the impediments associated with the conventional laparoscopic approach. RALS
      helps the relative novice to perform fine surgical techniques and is thought to
      reduce the learning curve associated with some surgical techniques, such as
      intracorporeal suturing, owing to the improved freedom of movement of the
      surgical instruments, the ergonomic positioning of the surgeon, and the 3D vision
      provided by the robotic system. Given the favourable safety profile and
      associated benefits of the robot system, including reductions in mean
      postoperative hospital stay compared with conventional procedures, RALS is
      becoming more widely adopted by paediatric urologists. 

PMID- 24100518
TI  - Andrology: unique insight into the physiological functions of testosterone.

PMID- 24100520
TI  - Energy and electron transfer processes in polymeric nanoparticles.
AB  - We report herein a study on photoinduced electron transfer (eT) and energy
      transfer (ET) processes occurring between 9-methylanthracene-acrylate (A) and N,N
      dimethylaniline-acrylate (D) derivatives incorporated into polymeric
      nanoparticles (NP). Five types of NPs were synthesized: PAD0, PAD25, PAD75, PD25,
      and PD75. All NPs are composed of a crosslinked polymer matrix of methyl
      methacrylate and ethylene glycol dimethacrylate. In addition, PAD0, PAD25 and
      PAD75 contain low doping levels of A. For PAD25 and PAD75, 25% and 75% of the
      mole fraction of methyl methacrylate is replaced by D, respectively. PD25 and
      PD75 were prepared as above but without A. NPs (diameter 6-9 nm) dispersed in
      organic solvents were characterized based on their UV-visible absorption,
      emission, excitation, and excitation anisotropy spectra and time dependent
      absorption and emission spectroscopy techniques. The emission decay profiles of A
      and D were always complex. Results indicate that A senses two distinct
      environments in all NPs. The emission quenching of PAD0 by DMA in DCM solutions
      is dynamic, and it is apparent that a significant fraction of A is inaccessible
      to the quencher. The emission of A is efficiently quenched by the presence of D
      in PAD25 and PAD75. The intra-NP photoinduced eT quenching mechanism has static
      and dynamic components. Selective excitation of D in PAD25 and PAD75 leads to the
      formation of the excited state of A via a singlet-singlet ET Foster type
      mechanism. Results indicate that both intra-NP eT and ET processes are more
      efficient in PAD75 due to the reduced average D*-A separation in these NPs. 

PMID- 24100522
TI  - Reliable PCR quantitation of estrogen, progesterone and ERBB2 receptor mRNA from
      formalin-fixed, paraffin-embedded tissue is independent of prior macro
      dissection.
AB  - Gene expression analysis on messenger RNA (mRNA) purified from formalin-fixed,
      paraffin-embedded tissue is increasingly used for research purposes. Tissue
      heterogeneity may question specificity and interpretation of results from mRNA
      isolated from a whole slide section, and thresholds for minimal tumor content in
      the paraffin block or macrodissection are used to avoid contamination from non
      neoplastic tissue. The aim was to test if mRNA from tissue surrounding breast
      cancer affected quantification of estrogen receptor alpha (ESR1), progesterone
      receptor (PGR) and human epidermal growth factor receptor 2 (ERBB2), by comparing
      gene expression from whole slide and tumor-enriched sections, and correlating
      gene expression from whole slide sections with corresponding
      immunohistochemistry. Gene expression, based on mRNA extracted from a training
      set (36 paraffin blocks) and two validation sets (133 + 1,083 blocks), were
      determined by quantitative reverse transcription polymerase chain reaction for
      all samples, as well as by microarray for 133 validation samples. In the training
      set, agreement between high vs. low mRNA expression from whole slide and tumor
      enriched sections was absolute for ESR1 and ERBB2, and 83 % for PGR. Overall
      agreements, when comparing mRNA expression to immunohistochemistry, were 100 %
      (ERBB2), 89 % (ESR1) and 83 % (PGR), which was confirmed in the validation sets.
      Percentage of tumor in the sections did not influence the results. In conclusion,
      reliable quantification of ESR1, PGR and ERBB2 mRNA expression can be obtained
      from a whole slide section, and correlates well with immunohistochemistry. Prior
      removal of surrounding tissue was found to be unnecessary even with minimal tumor
      content in the section.

PMID- 24100521
TI  - Pleiotropic constraints, expression level, and the evolution of miRNA sequences.
AB  - Post-transcriptional gene regulation mediated by microRNAs (miRNAs) plays
      critical roles during development by modulating gene expression and conferring
      robustness to stochastic errors. Phylogenetic analyses suggest that miRNA
      acquisition could play a role in phenotypic innovation. Moreover, miRNA-induced
      regulation strongly impacts genome evolution, increasing selective constraints on
      3'UTRs, protein sequences, and expression level divergence. Thus, it is essential
      to understand the factors governing sequence evolution for this important class
      of regulatory molecules. Investigation of the patterns of molecular evolution at
      miRNA loci have been limited in Caenorhabditis elegans because of the lack of a
      close outgroup. Instead, I used Caenorhabditis briggsae as the focus point of
      this study because of its close relationship to Caenorhabditis sp. 9. I also
      corroborated the patterns of sequence evolution in Caenorhabditis using published
      orthologous relationships among miRNAs in Drosophila. In nematodes and in flies,
      miRNA sequence divergence is not influenced by the genomic neighborhood (i.e.,
      intronic or intergenic) but is nevertheless affected by the genomic context
      because X-linked miRNAs evolve faster than autosomal miRNAs. However, this effect
      of chromosomal linkage can be explained by differential expression levels rather
      than a fast-X effect. The results presented here support a universal negative
      relationship between rates of molecular evolution and expression level, and
      suggest that mutations in highly expressed miRNAs are more likely to be
      deleterious because they potentially affect a larger number of target genes.
      Finally, I show that many single family member miRNAs evolve faster than miRNAs
      from multigene families and have limited functional scope, suggesting that they
      are not strongly integrated in gene regulatory networks. 

PMID- 24100523
TI  - Pulmonary inflammatory myofibroblastic tumor and IgG4-related inflammatory
      pseudotumor: a diagnostic dilemma.
AB  - IgG4-related inflammatory pseudotumor (IPT) and inflammatory myofibroblastic
      tumor (IMT) share morphological features like a prominent
      fibroblastic/myofibroblastic proliferation and the presence of inflammatory
      cells. Since IPT is managed conservatively and IMT is treated by surgical
      excision, it is important to differentiate these two lesions. The aim of this
      study is to highlight morphological and immunohistochemical features that
      distinguish IPT and IMT. Clinicopathological characteristics of cases diagnosed
      as pulmonary IPT or IMT from 1997 to 2013 were reviewed. The histological
      features were studied on hematoxylin and eosin-stained sections.
      Immunohistochemistry was done for IgG, IgG4, ALK-1, SMA, desmin, and CD34 for
      classification into IPT and IMT. Of the ten patients, seven were male and the age
      ranged from 4 to 58 years. The tumor size ranged from 1.5 to 4.0 cm in diameter.
      Histologically, proliferation of bland-looking spindle cells along with fibrosis
      and an inflammatory infiltrate comprising of lymphocytes and plasma cells were
      the common morphological features of both lesions. The spindle cell proliferation
      was more marked in IMT whereas lymphoplasmacytic infiltrate was more prominent in
      IPT. Obstructive phlebitis was observed only in cases of IPT. IgG4 expression was
      noted in IPT, and the number of IgG4-positive plasma cells and the ratio of
      IgG4+/IgG+ plasma cells were significantly lower in IMT than in IgG4-related IPT.
      Expression of anaplastic lymphoma kinase (ALK) was observed only in IMT, but not
      in IgG4-related IPT. The proportion of proliferating spindle cells,
      lymphoplasmacytic infiltrate, obstructive phlebitis, IgG4+ plasma cells and the
      ratio of IgG4+/IgG+ plasma cells, and ALK expression are helpful in
      differentiating these morphologically similar but biologically different lesions,
      which require different treatment modalities.

PMID- 24100525
TI  - Intercalation of chiral molecules into layered metal-organic frameworks: a
      strategy to synthesize homochiral MOFs.
AB  - Two homochiral SHG MOFs with remarkable layered architectures were prepared by
      intercalation of (S or R)-5-oxopyrrolidine-2-carboxylate into layered MOFs
      assembled from hydrogenated Schiff base L and Zn(II). This is a novel strategy to
      design and synthesize homochiral coordination polymers and potential nonlinear
      optical materials.

PMID- 24100524
TI  - Thoracoscopic and laparoscopic plication of the hemidiaphragm is effective in the
      management of diaphragmatic eventration.
AB  - PURPOSE: Diaphragmatic plication by minimally invasive surgery is thought to
      allow for a quick recovery and has been performed on small children. Here, we
      report our experience with different plication procedures to discuss how to
      choose among these different plication procedures in endoscopic surgery for
      pediatric patients with diaphragmatic eventration. PATIENTS AND METHODS: We
      retrospectively analyzed clinical data of 27 pediatric patients (21 boys, 6
      girls; median age: 12.7 months, range 2 months-3 years) admitted to our hospital
      between November 2008 and July 2013. Three different plication procedures were
      used: the "reefing the mainsail" technique (8 patients), "invaginating the
      diaphragmatic dome" technique (10 patients), and "pleating" technique (9
      patients). Indications included ventilator dependency (7.41 %), respiratory
      distress (22.22 %), chronic lung lobe collapse (11.11 %), persistent atelectasis
      with recurrent pneumonias (18.52 %), and asymptomatic severe eventration (40.74
      %). RESULTS: Descending distance of diaphragm after surgery ranged from 1 to 4.5
      intercostal spaces (mean distance: 2.65 intercostal spaces). All patients
      recovered well postoperatively, except for one patient with a pneumothorax. Two
      patients who required respiratory support before the operation no longer required
      it within 7 d after surgery. Follow-up ranged from 1 to 35 months. Clinical
      results were satisfactory with obvious improvement in symptoms and a slight re
      elevation within a distance of one intercostal space. CONCLUSION: For pediatric
      patients with diaphragmatic eventration, different endoscopic surgeries and
      plication procedures all yielded satisfactory results. We believe that the choice
      of one procedure over the other depends only on the surgeon's experience.

PMID- 24100526
TI  - Rotavirus vaccines, intussusception, and risk-benefit assessments.

PMID- 24100527
TI  - Case managers' retirement: what has reverse mentoring got to do with it?
AB  - With the aging case management workforce, bringing up younger professionals is a
      vitally current issue. This editorial focuses on the millennial generation of
      potential case managers, those born between 1980 and 2000, as these are the ages
      of the most likely "replacements." Traditional mentoring focuses on sponsorship
      and coaching. Is this enough to bring passion in the younger generation? Adding
      the model of "reverse mentoring" may be key in engaging these professionals.
      Reverse mentoring focuses on knowledge sharing and leadership development. 

PMID- 24100528
TI  - Care transitions programs: a review of hospital-based programs targeted to reduce
      readmissions.
AB  - PURPOSE/OBJECTIVES: An emphasis on a value-based payment model is expected to
      provide motivation for developing effective care transitions programs. For such
      programs to succeed, organizations must adopt an evidence-based, financially
      feasible model that enables improved coordination with providers, alignment of
      incentives, and measurement of key performance metrics, both clinical and
      operational. Evidence of cost-effective care transitions programs is important
      for deploying successful models broadly. PRIMARY PRACTICE SETTING(S): Hospital
      based programs. FINDINGS/CONCLUSIONS: Current literature on care transitions
      programs highlights different strategies, patient populations, settings, and
      outcomes; however, it lacks sufficient supporting financial evidence that these
      programs are operationally sustainable and cost-effective within current and
      projected reimbursement schemes. IMPLICATIONS FOR CASE MANAGEMENT PRACTICE: Care
      transitions interventions need to be further studied in different settings with
      different patient populations to identify the optimal approach(es). An additional
      opportunity for future investigation lies in translation of interventional
      programs targeted at readmission diseases in line for penalty by Medicare.

PMID- 24100530
TI  - The role and contributions of geriatric care managers: care recipients' views.
AB  - PURPOSE OF THE STUDY: To assess the value of geriatric care management (GCM)
      services from the perspective of individuals who receive the care--the "care
      recipients." The opinions of these older adults-the current users of GCM services
      -were investigated by means of a cross-sectional mail survey. PRIMARY PRACTICE
      SETTING: The study setting was the home of the care recipient of GCM services.
      METHODOLOGY AND SAMPLE: This cross-sectional descriptive study applied survey
      research design. Survey questions were developed related to the following themes
      about the GCM role and function: (1) overall role, (2) health assistance
      function, (3) community resources assistance function, (4) advocacy function, and
      (5) contribution to the care recipients' quality of life. Survey questionnaires
      were distributed to 179 care recipients of member organizations of the Florida
      Geriatric Care Management Association. The questionnaires were distributed by
      mail during the spring of 2012. A second mailing was completed in the fall of
      2012. The survey results were analyzed using descriptive statistics. RESULTS: The
      care recipient survey respondents most frequently described the role of their
      GCMs as one of a health care professional. The respondents more frequently
      described the GCM as providing a health assistance and advocacy function. They
      indicated that the GCM greatly contributed to their quality of life. IMPLICATIONS
      FOR CASE MANAGEMENT PRACTICE: Geriatric care managers appear to be very valuable
      in assisting their clients with critical health-related situations, as well as
      with more routine health care matters. Not only are they called upon to assist
      with health care emergencies and their clients' hospital stays but they also
      appear to serve an important role in facilitating physician-patient
      communications during the care recipient's routine visits to the doctor's office.

PMID- 24100532
TI  - Acute myocardial infarction rehospitalization of the medicare fee-for-service
      patient: a state-level analysis exploring 30-day readmission factors.
AB  - PURPOSE OF THE STUDY: Acute myocardial infarction (AMI) readmission among the
      older adults is frequent and costly to the Medicare Trust Fund and to the patient
      in preventable suffering. In this study, we explore factors that are associated
      with states having AMI readmission rates that are higher than the U.S. national
      rate. PRIMARY PRACTICE SETTING(S): Acute inpatient hospital settings. METHODOLOGY
      AND SAMPLE: Multivariate regression analysis of 50 state-level data is used. The
      dependent variable AMI 30-day readmission worse than U.S. rate is based on adult
      Medicare fee-for-service patients hospitalized with a primary discharge diagnosis
      of AMI and for which a subsequent all-cause readmission occurred within 30 days
      of their last discharge. RESULTS: We find one key variable--states with more beta
      blocker prescription given at discharge--that is significantly associated with a
      decrease in probability in states ranking "worse" on AMI 30-day readmission.
      Whereas, states with more total days of care per 1,000 Medicare enrollees, more
      community hospital outpatient visits per 1,000 population, and greater aspirin
      prescription given at discharge have a greater probability for AMI 30-day
      readmission to be "worse" than the U.S. national rate. IMPLICATIONS FOR CASE
      MANAGEMENT PRACTICE: Case management programs targeting efficient medication
      reconciliation from the hospital setting to the transfer setting can potentially
      help minimize readmission for patients highly dependent on beta-blockers for
      improved clinical outcomes. This intervention may be more effective than other
      factors to improve state-level hospital status on AMI 30-day readmission. Factors
      such as total days of care per 1,000 Medicare enrollees, more community hospital
      outpatient visits per 1,000 populations, and greater aspirin prescription given
      at discharge may not be as important as beta-blocker prescription given at
      discharge.

PMID- 24100533
TI  - Legal & regulatory issues.

PMID- 24100534
TI  - Vendor Credentialing: when RN licensing and certification are not enough.

PMID- 24100535
TI  - Guns, case management, and return to work.

PMID- 24100536
TI  - Case managing ourselves.

PMID- 24100537
TI  - Joan Park: leading the way for case management.

PMID- 24100538
TI  - Patient empowerment and health care reform.

PMID- 24100539
TI  - Anaemia management in patients with inflammatory bowel disease: routine practice
      across nine European countries.
AB  - BACKGROUND AND OBJECTIVES: Anaemia and iron deficiency (ID) are common
      complications in inflammatory bowel disease (IBD). In patients undergoing iron
      therapy, intravenous iron supplementation is recommended in preference to oral
      therapy. This study evaluated routine practice in the management of IBD
      associated anaemia and ID to verify implementation of international treatment
      guidelines. MATERIALS AND METHODS: Gastroenterologists from nine European
      countries (n=344) were surveyed about their last five IBD patients treated for
      anaemia (n=1404). Collected information included tests performed at anaemia
      diagnosis, haemoglobin (Hb) levels and iron status parameters, the anaemia
      treatment given and, if applicable, the iron administration route. RESULTS:
      Selection of diagnostic tests and treatment for IBD-associated anaemia varied
      considerably across Europe. Anaemia and iron status were mainly assessed by Hb
      (88%) and serum ferritin (75%). Transferrin saturation was only tested in 25% of
      patients. At diagnosis of anaemia, 56% presented with at least moderate anaemia
      (Hb<10 g/dl) and 15% with severe anaemia (Hb<8 g/dl). ID (ferritin<30 ng/ml) was
      detected in 76%. Almost all patients (92%) received iron supplementation;
      however, only 28% received intravenous iron and 67% oral iron. Management
      practice was similar in 2009 and 2011. CONCLUSION: In clinical practice, most IBD
      patients received oral iron even though this administration route may aggravate
      the disease, and despite international guidelines recommending intravenous
      administration as the preferred route. The high frequency of ID suggests
      insufficient monitoring of iron status in IBD patients. There is a need to
      increase awareness and implementation of international guidelines on iron
      supplementation in patients with IBD.

PMID- 24100540
TI  - Investigation of structure and dynamics of the hydrated metal-organic framework
      MIL-53(Cr) using first-principles molecular dynamics.
AB  - The hydration behavior of metal-organic frameworks (MOFs) is of interest both
      from a practical and from a fundamental point of view: it is linked, on the one
      hand, to the hydrothermal stability (or instability) of the nanoporous material,
      which might limit its use in technological applications. On the other hand, it
      sheds light on the behavior of water in a strongly confined environment. Here, we
      use first-principles molecular dynamics (MD) to investigate two hydrated phases
      of the flexible MOF MIL-53(Cr), which adopts a narrow- or a large-pore form,
      depending on the water loading. Structure and dynamics of the two phases are
      thoroughly analyzed and compared, with a focus on the hydroxyl group of MIL
      53(Cr) and the water molecules in the nanopores. Furthermore, the behavior of the
      confined water is compared to that of bulk water. Whereas in the narrow-pore
      form, water is adsorbed at specific crystalline sites, it shows a more
      disordered, bulk-like structure in the large-pore form. However, reorientation
      dynamics of water molecules in the latter is considerably slowed down with
      respect to bulk water, which highlights the confinement effect of the nanoporous
      framework. 

PMID- 24100541
TI  - Tip-enhanced near-field optical microscopy.
AB  - Tip-enhanced near-field optical microscopy (TENOM) is a scanning probe technique
      capable of providing a broad range of spectroscopic information on single objects
      and structured surfaces at nanometer spatial resolution and with highest
      detection sensitivity. In this review, we first illustrate the physical principle
      of TENOM that utilizes the antenna function of a sharp probe to efficiently
      couple light to excitations on nanometer length scales. We then discuss the
      antenna-induced enhancement of different optical sample responses including Raman
      scattering, fluorescence, generation of photocurrent and electroluminescence.
      Different experimental realizations are presented and several recent examples
      that demonstrate the capabilities of the technique are reviewed. 

PMID- 24100542
TI  - Ardnamurchan 3D cone-sheet architecture explained by a single elongate magma
      chamber.
AB  - The Palaeogene Ardnamurchan central igneous complex, NW Scotland, was a defining
      place for the development of the classic concepts of cone-sheet and ring-dyke
      emplacement and has thus fundamentally influenced our thinking on subvolcanic
      structures. We have used the available structural information on Ardnamurchan to
      project the underlying three-dimensional (3D) cone-sheet structure. Here we show
      that a single elongate magma chamber likely acted as the source of the cone-sheet
      swarm(s) instead of the traditionally accepted model of three successive centres.
      This proposal is supported by the ridge-like morphology of the Ardnamurchan
      volcano and is consistent with the depth and elongation of the gravity anomaly
      underlying the peninsula. Our model challenges the traditional model of cone
      sheet emplacement at Ardnamurchan that involves successive but independent
      centres in favour of a more dynamical one that involves a single, but elongate
      and progressively evolving magma chamber system. 

PMID- 24100543
TI  - Hypoxia-induced overexpression of DEC1 is regulated by HIF-1alpha in
      hepatocellular carcinoma.
AB  - Hypoxia-inducible factor-1alpha (HIF-1alpha) and differentiated embryo
      chondrocyte expressed gene 1 (DEC1) are two key factors that protect
      hepatocellular carcinoma (HCC) cells from a hypoxic microenvironment. However,
      little is known concerning the effects of hypoxia on the expression of HIF-1alpha
      and DEC1 in HCC. In the present study, RT-PCR and western blotting were conducted
      to assay the mRNA and protein levels of HIF-1alpha and DEC1 under normoxia and
      hypoxia induced by exposure to CoCl2 for different time periods (0, 2, 4, 6, 24
      and 48 h). In addition, the HIF-1alpha protein inhibitor, YC-1, was used to
      analyze the interaction between DEC1 and HIF-1alpha expression and the related
      mechanism. Results showed that expression of DEC1 in HCC was significantly
      upregulated at both the mRNA and protein levels, when compared with that in
      normal liver cells (P<0.05). Hypoxia induced the upregulation of HIF-1alpha in a
      time-dependent manner, which was also observed at the DEC1 mRNA and protein
      levels (P<0.05). However, hypoxia did not affect the transcription of HIF-1alpha
      (P>0.05). A positive correlation was found between HIF-1alpha and DEC1 expression
      in both BEL-7402 (r=0.885, P<0.05) and SMMC-7721 cells (r=0.826, P<0.05).
      Furthermore, inhibition of HIF-1alpha by YC-1 led to a significant decrease in
      DEC1 induced by hypoxia (P<0.05). We suggest that hypoxia induced the
      overexpression of DEC1, the mechanism of which may be related to the upregulation
      of HIF-1alpha in HCC. The efficacy of inhibiting HIF-1alpha and DEC1 expression
      as a possible treatment for HCC should be assessed in clinical trials.

PMID- 24100544
TI  - Better population health through behavior change in adults: a call to action.

PMID- 24100546
TI  - Copper-catalyzed oxidation of arene-fused cyclic amines to cyclic imides.
AB  - A novel copper-catalyzed oxidation of arene-fused cyclic amines to the
      corresponding cyclic imides has been developed. The reaction can be used to
      synthesize 1,3-disubstituted TPD in high yields. 

PMID- 24100545
TI  - Wide distribution of CREM immunoreactivity in adult and fetal human brain, with
      an increased expression in dentate gyrus neurons of Alzheimer's as compared to
      normal aging brains.
AB  - Human cyclic AMP response modulator proteins (CREMs) are encoded by the CREM
      gene, which generates 30 or more different CREM protein isoforms. They are
      members of the leucine zipper protein superfamily of nuclear transcription
      factors. CREM proteins are known to be implicated in a plethora of important
      cellular processes within the CNS. Amazingly, little is known about their
      cellular and regional distribution in the brain, however. Therefore, we studied
      by means of immunohistochemistry and Western blotting the expression patterns of
      CREM in developing and adult human brain, as well as in brains of Alzheimer's
      disease patients. CREM immunoreactivity was found to be widely but unevenly
      distributed in the adult human brain. Its localization was confined to neurons.
      In immature human brains, CREM multiple neuroblasts and radial glia cells
      expressed CREM. In Alzheimer's brain, we found an increased cellular expression
      of CREM in dentate gyrus neurons as compared to controls. We discuss our results
      with regard to the putative roles of CREM in brain development and in cognition.

PMID- 24100547
TI  - Use of in vivo biotinylated GST fusion proteins to select recombinant antibodies.
AB  - Over the last 20 years, continuous advances in the field of molecular biology
      have led to the development of new strategies to discover and produce monoclonal
      antibodies, notably by phage display.Here we describe a simple procedure for
      antibody selection that reduces considerably the undesired selection of non
      specific antibodies, based on the use of biotinylated GST proteins fused to a
      target antigenic sequence. This procedure was tested on a collection of 7
      different targets and resulted in the selection of a high percentage (71%) of
      antibodies specific for each target. This simple and effective in vitro procedure
      has a strong potential to replace animal immunization for the development of
      specific antibodies. 

PMID- 24100548
TI  - Distribution and neurochemical characterization of neurons in the rat
      ventrolateral medulla activated by glucoprivation.
AB  - Hypoglycemia elicits physiological and behavioral responses which are mediated in
      part by neurons within the ventrolateral medulla (VLM). The present study
      describes the neurochemistry of neurons activated by glucoprivation (2-deoxy-D
      glucose, 2DG), specifically those within regions containing the A1, caudal C1
      (cC1) and rostral C1 (rC1) cell groups. 2DG induced c-Fos immunoreactivity
      throughout the VLM. Activated neurons expressing prepro-cocaine and amphetamine
      regulated transcript (PPCART), neuropeptide Y (NPY), glutamic acid decarboxylase
      (GAD67) or prepro-enkephalin (PPE) mRNA and/or immunoreactivity (-ir) for
      tyrosine hydroxylase (TH) were identified. TH(+) neurons were recruited in a dose
      dependent manner. At high doses of 2DG [400 mg/kg, (n = 6)], 76 +/- 1.2 % of
      activated neurons were TH(+) representing 52 +/- 1.3 % of the total TH
      population. Virtually all activated neurons in the A1 and cC1 regions but only 60
      % in the rC1 region were TH(+). Within the A1 region, TH(+), TH(+)NPY(+) and
      TH(+)NPY(+)PPE(+) subpopulations were activated and likely regulate vasopressin,
      oxytocin, and corticotrophin releasing hormone (CRH) from the hypothalamus.
      Within the cC1 region, non-TH neurons, TH(+)NPY(+), TH(+)NPY(+)PPCART(+), and
      TH(+)NPY(+)PPE(+) subpopulations were activated, likely regulating autonomic
      hypothalamic neurons or CRH and thyrotropin releasing hormone secretion. Within
      the rC1 region, non-TH neurons (40 % of those activated) were predominantly
      PPE(+) and were recruited by higher 2DG doses. Of the TH(+) activated neurons in
      the rC1 region, many expressed PPCART and half expressed NPY. The activated
      spinally projecting population was almost entirely TH(+)PPCART(+) and is likely
      to regulate adrenaline and glucagon release. These data indicate that
      glucoprivation activates at least nine phenotypically distinct populations of
      neurons in the VLM.

PMID- 24100549
TI  - Origin and concept of medicine food homology and its application in modern
      functional foods.
AB  - The viewpoints of "medicine food homology" (MFH) conform to today's food
      requirements of returning to a natural and green healthy life. This paper aims to
      introduce the concept of MFH and its origin and evolution, and analyze the
      relationship between food and Chinese medicine. In this review, more than 80 MFH
      materials approved by China's Ministry of Health are listed and their effective
      ingredients are summarized in detail. Their treatment mechanism in TCM and
      western medicine are summarized too. Moreover, some new MFH resources that have
      been gradually developed are also introduced. MFH materials are a treasure house
      of functional factors for current functional foods. Innovative ideas for the
      development of MFH resources in current functional foods are prospected and
      discussed, such as taking advantage of Chinese diet theory, building a database
      for MFH varieties and developing new methods and technologies. At present, modern
      research for the development of MFH functional foods is still in its primary
      stage, there is still much work required in the popularization of the MFH concept
      and the development of new products. Knowledge and technological innovations in
      this area should be accelerated in the future to promote the modernization of
      MFH. 

PMID- 24100550
TI  - Effects of apatite particle size in two apatite/collagen composites on the
      osteogenic differentiation profile of osteoblastic cells.
AB  - The development of new osteoconductive bone substitute materials is expected in
      medicine. In this study, we attempted to produce new hydroxylapatite
      (HAP)/collagen (Col) composites using two HAP particles of different sizes and
      porcine type I collagen. The two HAP particles were either nano-sized (40 nm in
      average diameter; n-HAP) or had macro-pore sizes of 0.5-1.0 mm in length with
      fully interconnected pores (m-HAP). The aim of this study was to investigate the
      effects of apatite particle size in two HAP/Col composites on the osteogenic
      differentiation profile in osteoblast-like cells (SaOS-2). We created a collagen
      control sponge (Col) and two HAP/Col composite sponges (n-HAP/Col and m-HAP/Col)
      using freeze-drying and dehydrothermal cross-linking techniques, and then punched
      out samples of 6 mm in diameter and 1 mm in height. The SaOS-2 cells were
      cultured on three test materials for 1, 2, 3 and 4 weeks. Total RNA was extracted
      from the cultured cells and the expression of osteogenic differentiation-related
      genes was evaluated by reverse transcription PCR (RT-PCR) using primer sets of
      alkaline phosphatase (ALP), type 1 collagen (COL1), bone sialoprotein (BSP) and
      osteocalcin precursor [bone gamma-carboxyglutamate (gla) protein (BGLAP)] genes,
      as well as the beta-actin gene. The cells were also cultured on Col, n-HAP/Col
      and m-HAP/Col specimens for 1 and 4 weeks, and were then observed under a
      scanning electron microscope (SEM). The experimental results were as follows: RT
      PCR indicated that osteogenic differentiation, particularly the gene expression
      of BSP, was most accelerated when the cells were cultured on n-HAP/Col specimens,
      followed by m-HAP/Col, whilst the weakest accelaeration was observed when the
      cells were cultured on Col specimens. As shown by the SEM images, the SaOS-2
      cells were fibroblastic when cultured on Col specimens for up to 4 weeks; they
      were fibroblastic when cultured on n-HAP/Col specimens for 1 week, but appeared
      as spheroids, while actively phagocytizing n-HAP particles at 4 weeks; however,
      they appeared as deformed fibroblasts when cultured on m-HAP/Col specimens,
      detached from the particles. Despite limited experimental results, our study
      suggests that n-HAP/Col may be employed as a new osteoconductive bone substitute
      material. 

PMID- 24100551
TI  - Unexpected features in the Protein Data Bank entries 3qd1 and 4i8e: the
      structural description of the binding of the serine-rich repeat adhesin GspB to
      host cell carbohydrate receptor is not a solved issue.
AB  - The structure of a complex between a fragment of the adhesin GspB from
      Streptococcus gordonii and a disaccharide (PDB entries 3qd1 and 4i8e) has
      recently been proposed to identify the binding site for the sialyl-T antigen
      recognized by GspB. This structure exhibits numerous unrealistic and unusual
      features such as an excessive number of van der Waals clashes and a lack of
      correlation between atomic structure and experimental electron density. Here, it
      is shown that the crystallographic data can be fully explained by an alternative
      model, namely replacing the disaccharide with a buffer molecule. The conclusion
      is that the experimental data are likely to contain no information regarding the
      carbohydrate receptor binding site in GspB or the interaction of GspB with host
      cell receptors. 

PMID- 24100552
TI  - A monoclinic crystal form of casein kinase 1 delta.
AB  - Casein kinase 1 delta (CK1delta) is a regulatory enzyme in the mammalian
      circadian oscillator and represents a potential pharmacological target for
      modulating circadian rhythms. Crystal structures of four different polymorphs of
      CK1delta have previously been determined and this article reports the
      crystallization and structure determination of a new crystal form belonging to
      space group P21. Comparison of CK1delta crystal structures reveals few
      conformational differences within the C-terminal lobe, but more significant
      movements of the beta-sheet region of the N-terminal lobe were observed. 

PMID- 24100553
TI  - Structure of 2-keto-3-deoxy-D-manno-octulosonate-8-phosphate synthase from
      Pseudomonas aeruginosa.
AB  - Pseudomonas aeruginosa is a major cause of opportunistic infection and is
      resistant to most antibiotics. As part of efforts to generate much-needed new
      antibiotics, structural studies of enzymes that are critical for the virulence of
      P. aeruginosa but are absent in mammals have been initiated. 2-Keto-3-deoxy-D
      manno-octulosonate-8-phosphate synthase (KDO8Ps), also known as 2-dehydro-3
      deoxyphosphooctonate aldolase, is vital for the survival and virulence of P.
      aeruginosa. This enzyme catalyzes a key step in the synthesis of the
      lipopolysaccharide (LPS) of most Gram-negative bacteria: the condensation
      reaction between phosphoenolpyruvate (PEP) and arabinose 5-phosphate to produce 2
      keto-3-deoxy-D-manno-octulosonate-8-phosphate (KDO8P). This step is vital for the
      proper synthesis and assembly of LPS and the survival of P. aeruginosa. Here, the
      recombinant expression, purification and crystal structure of KDO8Ps from P.
      aeruginosa are presented. Orthorhombic crystals were obtained by vapor diffusion
      in sitting drops in the presence of 1 mM phosphoenlpyruvate. The structure
      reveals the prototypical alpha/beta TIM-barrel structure expected from this
      family of enzymes and contains a tetramer in the asymmetric unit. 

PMID- 24100554
TI  - Structure of succinyl-CoA:3-ketoacid CoA transferase from Drosophila
      melanogaster.
AB  - Succinyl-CoA:3-ketoacid CoA transferase (SCOT) plays a crucial role in ketone
      body metabolism. SCOT from Drosophila melanogaster (DmSCOT) was purified and
      crystallized. The crystal structure of DmSCOT was determined at 2.64 A resolution
      and belonged to space group P212121, with unit-cell parameters a=76.638,
      b=101.921, c=122.457 A, alpha=beta=gamma=90 degrees . Sequence alignment and
      structural analysis identified DmSCOT as a class I CoA transferase. Compared with
      Acetobacter aceti succinyl-CoA:acetate CoA transferase, DmSCOT has a different
      substrate-binding pocket, which may explain the difference in their substrate
      specificities.

PMID- 24100555
TI  - Crystallization and preliminary X-ray diffraction analysis of the flax cytokinin
      oxidase LuCKX1.1.
AB  - The plant hormones cytokinins play a central role in regulating cell division and
      developmental events. Cytokinin oxidase regulates the levels of these plant
      hormones by catalyzing their irreversible oxidation, which contributes to the
      regulation of various morpho-physiological processes controlled by cytokinins. In
      this study, the crystallization and preliminary X-ray diffraction analysis of the
      flax cytokinin oxidase LuCKX1.1 are reported. Plate-like crystals of LuCKX1.1
      were obtained using PEG 3350 as a precipitant and diffracted X-rays to 1.78 A
      resolution. The protein crystals have the symmetry of space group C2 and are most
      likely to contain two molecules per asymmetric unit. 

PMID- 24100556
TI  - Expression, purification and crystallization of the FP domain of the human F-box
      protein Fbxo7.
AB  - Fbxo7 is a conserved protein in higher eukaryotes that belongs to the F-box
      protein family. Fbxo7 is the substrate-recognition component of the SCFFbxo7
      (Skp1-Cul1-Fbox protein) E3 ubiquitin ligase. Besides the F-box motif, Fbxo7 also
      contains a C-terminal proline-rich region, an N-terminal ubiquitin-like domain
      and a novel FP (Fbxo7/PI31) domain preceding the F-box motif. The FP domains of
      Fbxo7 and the PI31 proteasome inhibitor mediate interaction between the two
      proteins. For structure determination of the FP domain of Fxbo7, a protein
      construct (amino acids 181-335) corresponding to the FP domain was expressed,
      purified and crystallized. The native and selenomethionine-labeled proteins
      crystallized in different crystal forms. Native and single-wavelength anomalous
      dispersion data sets with diffraction to 2.1 and 2.0 A resolution, respectively,
      have been collected and structure determination is in progress.

PMID- 24100557
TI  - Preliminary X-ray diffraction analysis of thermostable beta-1,4-mannanase from
      Aspergillus niger BK01.
AB  - beta-1,4-Mannanase (beta-mannanase) is a key enzyme in decomposing mannans, which
      are abundant components of hemicelluloses in the plant cell wall. Therefore,
      mannan hydrolysis is highly valuable in a wide array of industrial applications.
      beta-Mannanase isolated from Aspergillus niger BK01 (ManBK) was classified into
      glycoside hydrolase family GH5. ManBK holds great potential in biotechnological
      applications owing to its high thermostability. Here, ManBK was expressed and
      purified in Pichia pastoris and the recombinant protein was crystallized.
      Crystals belonging to the orthorhombic space group C2221, with unit-cell
      parameters a=93.58, b=97.05, c=147.84 A, were obtained by the sitting-drop vapour
      diffusion method and diffracted to 1.57 A resolution. Structure determination
      using molecular-replacement methods is in progress.

PMID- 24100558
TI  - Cloning, expression, purification, crystallization and preliminary X-ray
      diffraction analysis of SpyCEP, a candidate antigen for a vaccine against
      Streptococcus pyogenes.
AB  - Streptococcus pyogenes (Group A streptococcus; GAS) is an important human
      pathogen against which an effective vaccine does not yet exist. The S. pyogenes
      protein SpyCEP (S. pyogenes cell-envelope proteinase) is a surface-exposed
      subtilisin-like serine protease of 1647 amino acids. In addition to its auto
      protease activity, SpyCEP is capable of cleaving interleukin 8 and related
      chemokines, contributing to GAS immune-evasion strategies. SpyCEP is immunogenic
      and confers protection in animal models of GAS infections. In order to
      structurally characterize this promising vaccine candidate, several SpyCEP
      protein-expression constructs were designed, cloned, produced in Escherichia
      coli, purified by affinity chromatography and subjected to crystallization
      trials. Crystals of a selenomethionyl form of a near-full-length SpyCEP
      ectodomain were obtained. The crystals diffracted X-rays to 3.3 A resolution and
      belonged to space group C2, with unit-cell parameters a=139.2, b=120.4, c=104.3
      A, beta=111 degrees .

PMID- 24100559
TI  - Purification, crystallization and preliminary crystallographic studies of C
      terminal RNA recognition motif (RRM-3) of human ELAV-type RNA-binding protein 3
      (ETR-3).
AB  - Human embryonically lethal abnormal vision (ELAV)-type RNA-binding protein 3 (ETR
      3) has been implicated in many aspects of RNA-processing events including
      alternative splicing, stability, editing and translation. RNA recognition motif 3
      (RRM-3) is an independent C-terminal RNA-binding domain of ETR-3 that
      preferentially binds to UG-rich repeats of the nuclear or cytoplasmic pre-mRNA,
      and along with the other domains mediates the inclusion of cardiac troponin T (c
      TNT) exon 5 in embryonic muscle, which is otherwise excluded in the adult. In the
      present study, RRM-3 was cloned, overexpressed, purified and crystallized by the
      hanging-drop vapour-diffusion method. The crystals diffracted to 3 A resolution
      at the home source and belonged to space group P213, with unit-cell parameters
      a=b=c=118.5 A, alpha=beta=gamma=90 degrees . There were two molecules of RRM-3 in
      the asymmetric unit and the calculated Matthews coefficient (VM) was 6.35 A3 Da(
      1), with a solvent content of 80.62%. Initial phases were determined by molecular
      replacement.

PMID- 24100560
TI  - Cloning, overexpression, purification, crystallization and preliminary X-ray
      diffraction analysis of Rv0241c (HtdX) from Mycobacterium tuberculosis H37Rv.
AB  - Rv0241c (HtdX) is a putative (3R)-hydroxyacyl-CoA dehydratase of Mycobacterium
      tuberculosis. The htdX gene belongs to a conserved operon and is expressed in
      mycobacteria in the presence of several fatty-acid synthase II drugs. To
      elucidate the structure of HtdX, the protein was cloned, overexpressed, purified
      to homogeneity and crystallized. The protein was crystallized from two
      conditions: (i) 3 M sodium chloride, 0.1 M Na HEPES pH 8.0 and (ii) 2.5 M sodium
      chloride, 0.1 M Tris-HCl pH 8.5. A complete diffraction data set was collected
      from crystals from both conditions. The crystal from the first condition
      diffracted to 2.3 A resolution and belonged to space group I41, with unit-cell
      parameters a=b=61.51, c=143.81 A. Crystals from the second condition diffracted
      to 3.1 A resolution and belonged to space group P43212 or P41212, with unit-cell
      parameters a=b=63.67, c=140.88 A. Both crystals contained one molecule in the
      asymmetric unit.

PMID- 24100561
TI  - Crystallization and preliminary crystallographic analysis of GanB, a GH42
      intracellular beta-galactosidase from Geobacillus stearothermophilus.
AB  - Geobacillus stearothermophilus T-6 is a Gram-positive thermophilic soil bacterium
      that contains a multi-enzyme system for the utilization of plant cell-wall
      polysaccharides, including xylan, arabinan and galactan. The bacterium uses a
      number of endo-acting extracellular enzymes that break down the high-molecular
      weight polysaccharides into decorated oligosaccharides. These oligosaccharides
      enter the cell and are further hydrolyzed into sugar monomers by a set of
      intracellular glycoside hydrolases. One of these intracellular degrading enzymes
      is GanB, a glycoside hydrolase family 42 beta-galactosidase capable of
      hydrolyzing short beta-1,4-galactosaccharides to galactose. GanB and related
      enzymes therefore play an important part in the hemicellulolytic utilization
      system of many microorganisms which use plant biomass for growth. The interest in
      the biochemical characterization and structural analysis of these enzymes stems
      from their potential biotechnological applications. GanB from G.
      stearothermophilus T-6 has recently been cloned, overexpressed, purified,
      biochemically characterized and crystallized in our laboratory as part of its
      complete structure-function study. The best crystals obtained for this enzyme
      belong to the primitive orthorhombic space group P212121, with average
      crystallographic unit-cell parameters of a=71.84, b=181.35, c=196.57 A. Full
      diffraction data sets to 2.45 and 2.50 A resolution have been collected for both
      the wild-type enzyme and its E323A nucleophile catalytic mutant, respectively, as
      measured from flash-cooled crystals at 100 K using synchrotron radiation. These
      data are currently being used for the full three-dimensional crystal structure
      determination of GanB.

PMID- 24100562
TI  - Expression, crystallization and preliminary X-ray crystallographic analysis of
      peptide deformylase from Campylobacter jejuni.
AB  - Campylobacter jejuni is one of the major foodborne pathogens causing human
      infection. Peptide deformylase, a metallohydrolase, catalyzes the deformylation
      of N-formylated methionine in newly synthesized polypeptides in prokaryotes and
      some eukaryotic organelles. The deformylation process is an essential step in
      protein synthesis and has attracted much attention as a potential target for the
      development of novel antibacterial agents. Here, the cloned codon-optimized def
      gene from C. jejuni was synthesized and the protein was expressed, purified and
      crystallized. C. jejuni peptide deformylase crystals obtained at pH 7.0 and pH
      6.5 diffracted to 2.9 A resolution and belonged to the trigonal space group R3,
      with unit-cell parameters a=b=105.7, c=58.0 A. One monomer existed in the
      asymmetric unit, with a corresponding VM of 3.1 A3 Da(-1) and a solvent content
      of 60.4%.

PMID- 24100563
TI  - Identification, characterization and preliminary X-ray diffraction analysis of
      the rolling-circle replication initiator protein from plasmid pSTK1.
AB  - Antibiotic resistance in bacterial pathogens poses an ever-increasing risk to
      human health. In antibiotic-resistant strains of Staphylococcus aureus this
      resistance often resides in extra-chromosomal plasmids, such as those of the
      pT181 family, which replicate via a rolling-circle mechanism mediated by a
      plasmid-encoded replication initiation protein. Currently, there is no structural
      information available for the pT181-family Rep proteins. Here, the
      crystallization of a catalytically active fragment of a homologous replication
      initiation protein from the thermophile Geobacillus stearothermophilus
      responsible for the replication of plasmid pSTK1 is reported. Crystals of the
      RepSTK1 fragment diffracted to a resolution of 2.5 A and belonged to space group
      P212121.

PMID- 24100564
TI  - Overexpression, crystallization and preliminary X-ray crystallographic analysis
      of a putative xylose isomerase from Bacteroides thetaiotaomicron.
AB  - Bacteroides thetaiotaomicron BT0793, a putative xylose isomerase, was
      overexpressed in Escherichia coli, purified and crystallized using polyethylene
      glycol monomethyl ether 550 as the precipitant. X-ray diffraction data were
      collected to 2.10 A resolution at 100 K using synchrotron X-rays. The crystal was
      found to belong to space group P1, with unit-cell parameters a=96.3, b=101.7,
      c=108.3 A, alpha=82.8, beta=68.2, gamma=83.0 degrees . The asymmetric unit
      contained eight subunits of xylose isomerase with a crystal volume per protein
      weight (VM) of 2.38 A3 Da(-1) and a solvent content of 48.3%.

PMID- 24100565
TI  - Crystallization and preliminary X-ray diffraction studies of D-threo-3
      hydroxyaspartate dehydratase isolated from Delftia sp. HT23.
AB  - D-threo-3-Hydroxyaspartate dehydratase (D-THA DH) isolated from the soil
      bacterium Delftia sp. HT23 is a novel enzyme consisting of 380 amino-acid
      residues which catalyzes the conversion of D-threo-3-hydroxyaspartate to
      oxaloacetate and ammonia. D-THA DH also catalyzes the dehydration of L-threo-3
      hydroxyaspartate, L-erythro-3-hydroxyaspartate and D-serine. The amino-acid
      sequence of D-THA DH shows significant similarity to that of two eukaryotic D
      serine dehydratases derived from Saccharomyces cerevisiae and chicken kidney. D
      THA DH is classified into the fold-type III group of pyridoxal enzymes and is the
      first example of a fold-type III dehydratase derived from a prokaryote.
      Overexpression of recombinant D-THA DH was carried out using a Rhodococcus
      erythropolis expression system and the obtained protein was subsequently purified
      and crystallized. The crystals of D-THA DH belonged to space group I4122, with
      unit-cell parameters a=b=157.3, c=157.9 A. Single-wavelength anomalous
      diffraction data were collected to a resolution of 2.0 A using synchrotron
      radiation at the wavelength of the Br K absorption edge.

PMID- 24100566
TI  - Crystallization of the C-terminal head domain of the fibre protein from a
      siadenovirus, turkey adenovirus 3.
AB  - Turkey adenovirus 3 belongs to the genus Siadenovirus. Its predicted fibre
      protein consists of an N-terminal virus-attachment domain, a central shaft domain
      and a head domain at the C-terminus. The head domain has little sequence identity
      to known adenovirus fibre head structures. Crystals of the fibre head domain
      consisting of amino acids 304-454 with an N-terminal purification tag were
      produced. Crystals of native and selenomethionine-derivatized protein belonged to
      space group I23 (unit-cell parameter 99 A). They diffracted synchrotron radiation
      to 2.0 and 2.14 A resolution, respectively, and are expected to contain one
      monomer in the asymmetric unit. 

PMID- 24100567
TI  - Crystallization and preliminary X-ray study of a (2R,3R)-2,3-butanediol
      dehydrogenase from Bacillus coagulans 2-6.
AB  - (2R,3R)-2,3-Butanediol dehydrogenase (R,R-BDH) from Bacillus coagulans 2-6 is a
      zinc-dependent medium-chain alcohol dehydrogenase. Recombinant R,R-BDH with a
      His6 tag at the C-terminus was expressed in Escherichia coli BL21 (DE3) cells and
      purified by Ni2+-chelating affinity and size-exclusion chromatography. Crystals
      were grown by the hanging-drop vapour-diffusion method at 289 K. The
      crystallization condition consisted of 8%(v/v) Tacsimate pH 4.6, 18%(w/v)
      polyethylene glycol 3350. The crystal diffracted to 2.8 A resolution in the
      orthorhombic space group P212121, with unit-cell parameters a=88.35, b=128.73,
      c=131.03 A.

PMID- 24100568
TI  - Crystallization and preliminary X-ray diffraction analysis of a high-affinity
      phosphate-binding protein endowed with phosphatase activity from Pseudomonas
      aeruginosa PAO1.
AB  - In prokaryotes, phosphate starvation induces the expression of numerous phosphate
      responsive genes, such as the pst operon including the high-affinity phosphate
      binding protein (PBP or pstS) and alkaline phosphatases such as PhoA. This
      response increases the cellular inorganic phosphate import efficiency. Notably,
      some Pseudomonas species secrete, via a type-2 secretion system, a phosphate
      binding protein dubbed LapA endowed with phosphatase activity. Here, the
      expression, purification, crystallization and X-ray data collection at 0.87 A
      resolution of LapA are described. Combined with biochemical and enzymatic
      characterization, the structure of this intriguing phosphate-binding protein will
      help to elucidate the molecular origin of its phosphatase activity and to
      decipher its putative role in phosphate uptake. 

PMID- 24100569
TI  - Crystallization and preliminary crystallographic analysis of a viral RNA
      silencing suppressor encoded by Wuhan nodavirus.
AB  - Wuhan nodavirus (WhNV), which is a new member of the Nodaviridae family, encodes
      a viral protein, B2, that suppresses RNA silencing and host-cell RNA interference
      (RNAi)-mediated immunity. Although Flock House virus (FHV), another member of the
      Nodaviridae family, also produces a B2 protein with a similar function, the
      primary sequences of the B2 proteins from WhNV and FHV have no similarity. To
      gain a better understanding of the structural details and the mechanism of
      suppression of RNA silencing by WhNV B2 and to compare it with FHV B2,
      recombinant WhNV B2 protein has been overexpressed in Escherichia coli, purified
      and crystallized at 291 K using PEG 4000 as a precipitant. A 2.8 A resolution
      data set has been collected from a single crystal at 100 K. This crystal belonged
      to space group P212121, with unit-cell parameters a=27.3, b=45.6, c=133.9 A,
      alpha=beta=gamma=90 degrees . Assuming the presence of two molecules in the
      asymmetric unit, the Matthews coefficient is 2.2 A3 Da(-1).

PMID- 24100570
TI  - Crystallization and X-ray diffraction analysis of nylon hydrolase (NylC) from
      Arthrobacter sp. KI72.
AB  - Nylon hydrolase (NylC) encoded by Arthrobacter plasmid pOAD2 (NylCp2) was
      expressed in Escherichia coli JM109 and purified by ammonium sulfate
      fractionation, anion-exchange column chromatography and gel-filtration
      chromatography. NylCp2 was crystallized by the sitting-drop vapour-diffusion
      method with ammonium sulfate as a precipitant in 0.1 M HEPES buffer pH 7.5
      containing 0.2 M NaCl and 25% glycerol. Diffraction data were collected from the
      native crystal to a resolution of 1.60 A. The obtained crystal was spindle shaped
      and belonged to the C-centred orthorhombic space group C2221, with unit-cell
      parameters a=70.84, b=144.90, c=129.05 A. A rotation and translation search gave
      one clear solution containing two molecules per asymmetric unit.

PMID- 24100571
TI  - Expression, purification and preliminary X-ray crystallographic analysis of Arf1
      GDP in complex with dimeric p23 peptide.
AB  - Arf1 is a member of the Ras superfamily and is involved in COPI vesicle
      formation. Arf1-GDP can interact with dimeric p23. Here, human Arf1 (residues 18
      181) was cloned, expressed and purified in Escherichia coli. For crystallization,
      Arf1-GDP was mixed with dimeric p23 peptide in a 1:5 molar ratio. Crystals were
      obtained which diffracted to 2.7 A resolution. The crystals belonged to space
      group P6122, with unit-cell parameters a=b=80.6, c=336.0 A, alpha=beta=90,
      gamma=120 degrees . The asymmetric unit of the crystals contained two molecules,
      with a Matthews coefficient of 3.2 A3 Da(-1) and a solvent content of 61.9%.

PMID- 24100572
TI  - Purification, crystallization and preliminary X-ray crystallographic analysis of
      the transport unit of the monomeric autotransporter AIDA-I from Escherichia coli.
AB  - The adhesin involved in diffuse adherence (AIDA-I) from Escherichia coli belongs
      to the group of autotransporters, specifically the type Va secretion system
      (T5aSS). All autotransporter systems contain a C-terminal beta-domain, which
      forms a barrel-like structure in the outer membrane with a hydrophilic pore
      allowing passenger translocation across the outer membrane. The passenger domain
      harbours the biological activity in the extracellular space and functions, for
      example, as an adhesin, an enzyme and a toxin. The exact transport mechanism of
      passenger translocation across the outer membrane is not clear at present. Thus,
      structure determination of the transport unit of AIDA-I could provide new
      insights into the transport mechanism. Here, the purification, crystallization
      and preliminary X-ray crystallographic studies of the transport unit of AIDA-I
      are reported. 

PMID- 24100573
TI  - Expression, crystallization and preliminary X-ray crystallographic analysis of
      cellobiose 2-epimerase from Dictyoglomus turgidum DSM 6724.
AB  - Cellobiose 2-epimerase epimerizes and isomerizes beta-1,4- and alpha-1,4-gluco
      oligosaccharides. N-Acyl-D-glucosamine 2-epimerase (DT_epimerase) from
      Dictyoglomus turgidum has an unusually high catalytic activity towards its
      substrate cellobiose. DT_epimerase was expressed, purified and crystallized.
      Crystals were obtained of both His-tagged DT_epimerase and untagged DT_epimerase.
      The crystals of His-tagged DT_epimerase diffracted to 2.6 A resolution and
      belonged to the monoclinic space group P21, with unit-cell parameters a=63.9,
      b=85.1, c=79.8 A, beta=110.8 degrees . With a Matthews coefficient VM of 2.18 A3
      Da(-1), two protomers were expected to be present in the asymmetric unit with a
      solvent content of 43.74%. The crystals of untagged DT_epimerase diffracted to
      1.85 A resolution and belonged to the orthorhombic space group P212121, with unit
      cell parameters a=55.9, b=80.0, c=93.7 A. One protomer in the asymmetric unit was
      expected, with a corresponding VM of 2.26 A3 Da(-1) and a solvent content of
      45.6%.

PMID- 24100574
TI  - Cloning, expression, purification, crystallization and preliminary X-ray
      crystallographic analysis of the TIR domain from the Brucella melitensis TIR
      domain-containing protein TcpB.
AB  - In mammals, Toll-like receptors (TLRs) recognize conserved microbial molecular
      signatures and induce an early innate immune response in the host. TLR signalling
      is mediated by interactions between the cytosolic TIR (Toll/interleukin-1
      receptor) domains of the receptor and the adaptor proteins. Increasingly, it is
      apparent that pathogens target this interaction via pathogen-expressed TIR-domain
      containing proteins to modulate immune responses. A TIR-domain-containing protein
      TcpB has been reported in the pathogenic bacterium Brucella melitensis. Studies
      have shown that TcpB interferes with the TLR2 and TLR4 signalling pathways to
      inhibit TLR-mediated inflammatory responses. Such interference may involve TIR
      TIR-domain interactions between bacterial and mammalian proteins, but there is a
      lack of information about these interactions at the molecular level. In this
      study, the cloning, expression, purification, crystallization and preliminary X
      ray crystallographic analysis of the protein construct corresponding to the TIR
      domain of TcpB (residues 120-250) are reported. The crystals diffracted to 2.6 A
      resolution, have the symmetry of the monoclinic space group P21 and are most
      likely to contain four molecules in the asymmetric unit. The structure should
      help in understanding the molecular basis of how TcpB affects the innate immunity
      of the host.

PMID- 24100575
TI  - Crystallization and preliminary structural characterization of the two actin
      isoforms of the malaria parasite.
AB  - Malaria is a devastating disease caused by apicomplexan parasites of the genus
      Plasmodium that use a divergent actin-powered molecular motor for motility and
      invasion. Plasmodium actin differs from canonical actins in sequence, structure
      and function. Here, the purification, crystallization and secondary-structure
      analysis of the two Plasmodium actin isoforms are presented. The recombinant
      parasite actins were folded and could be purified to homogeneity. Plasmodium
      actins I and II were crystallized in complex with the gelsolin G1 domain; the
      crystals diffracted to resolutions of 1.19 and 2.2 A and belonged to space groups
      P212121 and P21, respectively, each with one complex in the asymmetric unit.

PMID- 24100577
TI  - Purification, crystallization and preliminary crystallographic analysis of the
      SpaA backbone-pilin subunit from probiotic Lactobacillus rhamnosus GG.
AB  - Lactobacillus rhamnosus GG, a widely used Gram-positive probiotic strain, is
      clinically well known for its perceived health-promoting effects. It has recently
      been shown to display proteinaceous pilus fibres (called SpaCBA) on its cell
      surface. Structurally, SpaCBA pili possess a characteristic three-pilin
      polymerized architecture, with repeating SpaA major pilins that form the backbone
      and two types of minor subunits (SpaB and SpaC). In this study, recombinant SpaA
      protein was purified, characterized and crystallized. The crystals diffracted to
      a resolution of 2.0 A and belonged to space group C2, with unit-cell parameters
      a=227.9, b=63.2, c=104.3 A, beta=95.1 degrees .

PMID- 24100576
TI  - Cloning to crystallization of dihydrodipicolinate synthase from the intracellular
      pathogen Legionella pneumophila.
AB  - Dihydrodipicolinate synthase (DHDPS) catalyses the rate-limiting step in the
      biosynthesis of meso-diaminopimelate and lysine. Here, the cloning, expression,
      purification and crystallization of DHDPS from the intracellular pathogen
      Legionella pneumophila are described. Crystals grown in the presence of high
      molecular-weight PEG precipitant and magnesium chloride were found to diffract
      beyond 1.65 A resolution. The crystal lattice belonged to the hexagonal space
      group P6122, with unit-cell parameters a=b=89.31, c=290.18 A, and contained two
      molecules in the asymmetric unit. The crystal structure was determined by
      molecular replacement using a single chain of Pseudomonas aeruginosa DHDPS as the
      search model.

PMID- 24100578
TI  - Crystallization and preliminary X-ray diffraction studies of Tyr167His mutant
      alpha-cyclodextrin glucanotransferase from Bacillus macerans.
AB  - Improving the specificity of alpha-cyclodextrin glucanotransferase is a
      significant issue in the field of alpha-cyclodextrin production. In this study, a
      constructed Y167H mutant alpha-cyclodextrin glucanotransferase with enhanced
      alpha-cyclodextrin specificity was successfully expressed and purified. Single
      crystals were grown using PEG 4000 as a precipitating agent by the hanging-drop
      vapour-diffusion method at 293 K. The crystals exhibited two kinds of morphology
      in different crystallization conditions. The crystals diffracted to at least 2.2
      A resolution (space group P212121), with unit-cell parameters a=65.69, b=78.70,
      c=137.00 A. Assuming the asymmetric cell to be occupied by a monomer of 75 kDa,
      the unit cell contains 43.77% solvent with a crystal volume per protein mass, VM,
      of 2.19 A3 Da(-1).

PMID- 24100579
TI  - Comparison of the activity of three different HSP70 inhibitors on apoptosis, cell
      cycle arrest, autophagy inhibition, and HSP90 inhibition.
AB  - The chaperone HSP70 promotes the survival of cells exposed to many different
      types of stresses, and is also potently anti-apoptotic. The major stress-induced
      form of this protein, HSP70-1, is overexpressed in a number of human cancers, yet
      is negligibly expressed in normal cells. Silencing of the gene encoding HSP70-1
      (HSPA1A) is cytotoxic to transformed but not normal cells. Therefore, HSP70 is
      considered to be a promising cancer drug target, and there has been active
      interest in the identification and characterization of HSP70 inhibitors for
      cancer therapy. Because HSP70 behaves in a relatively non-specific manner in the
      control of protein folding, to date there are no reliably-identified "clients" of
      this protein, nor is there consensus as to what the phenotypic effects of HSP70
      inhibitors are on a cancer cell. Here for the first time we compare three
      recently-identified HSP70 inhibitors, PES-Cl, MKT-077, and Ver-155008, for their
      ability to impact some of the known and reported functions of this chaperone;
      specifically, the ability to inhibit autophagy, to influence the level of HSP90
      client proteins, to induce cell cycle arrest, and to inhibit the enzymatic
      activity of the anaphase-promoting complex/cyclosome (APC/C). We report that all
      three of these compounds can inhibit autophagy and cause reduced levels of HSP90
      client proteins; however, only PES-Cl can inhibit the APC/C and induce G 2/M
      arrest. Possible reasons for these differences, and the implications for the
      further development of these prototype compounds as anti-cancer agents, are
      discussed. 

PMID- 24100580
TI  - Functional impact of colorectal cancer-associated mutations in the transcription
      factor E2F4.
AB  - The transcription factor E2F4 plays a critical role in cell cycle progression of
      normal and cancerous intestinal epithelial cells. Contrary to other E2Fs, the
      coding region of the E2F4 gene contains a longer spacer segment of a CAG
      trinucleotide repeat sequence encoding 13 consecutive serine residues, which is
      highly vulnerable to frameshift mutations in situations of genetic instability.
      Mutations in this region of the E2F4 gene have been observed in colorectal tumors
      with microsatellite instability. However, the effect of these changes on its
      function in colorectal cancer cells is currently unknown. We generated
      E2F4(CAG)12 and E2F4(CAG)14 mutants and compared their activity to the E2F4 wild
      type, E2F4(CAG)13. Luciferase assays with the thymidine kinase-luc reporter gene
      revealed that the mutants were more transcriptionally active than wild-type E2F4.
      The mechanism of increased activity of E2F4 was primarily related to protein
      stability, due to a significantly enhanced half-life of E2F4 mutants
      comparatively to that of wild-type E2F4. However, the association with the pocket
      protein p130/RBL2 did not account for this increased protein stability.
      Sequencing analysis of the endogenous E2F4 gene in a series of colorectal cancer
      cell lines showed that the microsatellite-unstable cell line SW48 exhibited a
      serine deletion in this gene. Accordingly, E2F4 half-life was much more elevated
      in SW48 cells in comparison to Caco-2/15, a microsatellite-stable cell line.
      Notably, in soft-agar assays, both mutants more potently increased anchorage
      independent growth in comparison to wild-type E2F4. In conclusion, our data
      demonstrate that cancer-associated E2F4 mutations enhance the capacity of
      colorectal cancer cells to grow without anchorage, thereby contributing to tumor
      progression.

PMID- 24100581
TI  - Merging the best of both worlds: hybrid lipid-enveloped matrix nanocomposites in
      drug delivery.
AB  - The advent of nanotechnology has revolutionized drug delivery in terms of
      improving drug efficacy and safety. Both polymer-based and lipid-based drug
      loaded nanocarriers have demonstrated clinical benefit to date. However, to
      address the multifaceted drug delivery challenges ahead and further expand the
      spectrum of therapeutic applications, hybrid lipid-polymer nanocomposites have
      been designed to merge the beneficial features of both polymeric drug delivery
      systems and liposomes in a single nanocarrier. This review focuses on different
      classes of nanohybrids characterized by a drug-loaded polymeric matrix core
      enclosed in a lipid shell. Various nanoengineering approaches to obtain lipid
      polymer nanocomposites with a core-shell nanoarchitecture will be discussed as
      well as their predominant applications in drug delivery. 

PMID- 24100583
TI  - Systems approach to understand the immune response in tuberculosis: an iterative
      process between mouse models and human disease.
AB  - Tuberculosis remains a disease of considerable mortality and morbidity. The
      immune response determining whether individuals infected with the pathogen
      Mycobacterium tuberculosis control the infection, and remain latent, or go on to
      develop active tuberculosis disease is poorly understood. Our studies used
      microarray technology to derive blood transcriptional profiles of the host
      response during tuberculosis, which, combined with data from experimental
      systems, highlighted a potentially detrimental role for Type I interferons during
      infection, with important implications for vaccine and therapeutic development.
      Our studies have also provided candidate biomarkers, which may advance diagnosis
      and treatment monitoring. These studies thus exemplify the promise of a systems
      biology approach to understand the immune response to complex infectious disease
      such as tuberculosis, leading to improved experimental models and systems for
      improving our mechanistic understanding of why some individuals control the
      infection whereas others go on to develop active disease. 

PMID- 24100582
TI  - A modified model of T-cell differentiation based on mTOR activity and metabolism.
AB  - Current models of T-helper-cell differentiation depict the generation of effector
      cells from a naive T cell based on the cytokine environment upon T-cell-receptor
      engagement. We propose a new model of CD4(+) T-cell activation, differentiation,
      and function whereby the outcome of antigen recognition is dictated by mTOR
      activity and the subsequent up-regulation of selective metabolic function. Such a
      model more readily explains the generation of effector and memory cells including
      the concept of effector and memory Foxp3(+) regulatory cells. 

PMID- 24100584
TI  - Pathogen-sensing, regulatory T cells, and responsiveness-tuning collectively
      regulate foreign- and self-antigen mediated T-cell responses.
AB  - The concept that induction of T-cell-dependent immune responses requires both T
      cell recognition of an epitope and recognition by the innate immune system of
      pathogen-associated molecular patterns needs to be extended to include the
      contribution of regulatory T cells and of responsiveness-tuning. Here we develop
      the hypothesis that both pathogen sensing and regulatory T cells act on antigen
      presenting dendritic cells (DCs) to determine whether the DCs will be competent
      to activate T cells with cognate receptors. Tregs that recognize self
      peptide/major histocompatibility complexes (MHCs) on the DC in question will
      serve to inactivate that DC, whereas sensing of pathogens or innate "danger"
      signals by the DC will oppose the action of the Tregs. The responsiveness of the
      T-cell compartment is further controlled by activation-threshold tuning in which
      responsiveness is adjusted to the strength of recurrent stimulation of T cells by
      self-peptide/MHCs in the periphery. Thus, a robust T-cell response depends on T
      cell recognition of a peptide/MHC presented by a competent DC, competence
      depending on interactions with Tregs and the degree of innate stimulation through
      pathogen sensing, and on a combined TCR and accessory-signaling strength of
      stimulation that exceeds the activation threshold of the T cells, determined by
      its responsiveness tuning. 

PMID- 24100585
TI  - Encoding immunological memory in the initiation of B-cell receptor signaling.
AB  - In one of the earliest events in the initiation of antigen-driven antibody
      responses, naive, IgM-, and IgD-expressing B cells enter germinal centers where
      they irreversibly isotype switch to the expression of predominately IgG B-cell
      receptors (BCRs). The IgG-expressing B cells then undergo rounds of antigen
      driven selection, ultimately exiting germinal centers as IgG-expressing memory B
      cells or plasma blast. This early switch from IgM to IgG begs the question: Of
      what advantage to the memory response is the B cell's expression of an IgG BCR?
      Despite convincing evidence that the expression of IgG BCRs is essential for
      antibody memory responses in vivo, the molecular basis of this requirement is
      only incompletely understood. Here we describe intrinsic features of IgG BCRs
      that endow memory B cells with the ability to rapidly and efficiently initiate
      signaling. Remarkably, efficient signaling is mediated through the cytoplasmic
      tail of the membrane IgG that binds to synapse associated protein 97, a member of
      a large family of proteins that are best studied for their role in regulating
      receptor signaling in neuronal synapses. These findings underscore an interesting
      parallel in the mechanisms at play in encoding immunological memory and memory in
      the nervous system. 

PMID- 24100587
TI  - One-pot, single-step deracemization of 2-hydroxyacids by tandem biocatalytic
      oxidation and reduction.
AB  - A facile and efficient one-pot, single-step method for deracemizing a broad range
      of 2-hydroxyacids to (R)-2-hydroxyacids was established by combination of resting
      cells of an (S)-hydroxyacid dehydrogenase-producing microorganism and an (R)
      ketoacid reductase-producing microorganism. 

PMID- 24100588
TI  - The effects of anemia and blood transfusion on patients with stage III-IV ovarian
      cancer.
AB  - OBJECTIVES: The objective of this study was to examine the overall and recurrence
      free survival in patients with advanced ovarian cancer based on hemoglobin and
      blood transfusions. METHODS: A retrospective chart review was performed between
      2003 and 2007 on patients with pathologically confirmed stage 3-4 ovarian,
      fallopian, or peritoneal cancers. Data were collected on date of diagnosis,
      recurrence and death, stage, grade, age, surgery, estimated blood loss,
      hemoglobin (nadir and average levels), and number of blood transfusions. RESULTS:
      Two hundred sixteen patients were included in the final analysis. In the
      perichemotherapy, perioperative, and total time frames, 88%, 81%, and 95% of
      patients were anemic, and 9%, 22%, and 26% of the patients had severe anemia.
      After adjusting for age, stage, and optimal debulking status, the
      perichemotherapy hemoglobin level as a continuous variable was weakly associated
      with recurrence-free survival (adjusted hazard ratio [AHR], 0.98; P = 0.03), and
      as a categorical variable with both recurrence-free survival (AHR, 2.49; P =
      0.003) and overall survival (AHR, 1.91; P = 0.02). The total number of
      transfusions was also weakly associated with poor recurrence-free survival (AHR,
      1.06; P = 0.03). CONCLUSIONS: Our study is a retrospective analysis of the
      effects of anemia and transfusion on ovarian cancer. The rates of anemia in
      chemotherapy patients are higher than previously reported. Although maintaining
      average hemoglobin greater than 80 g/L during chemotherapy portends an improved
      overall survival, blood transfusion does not have any effect. The role of
      transfusion should therefore be limited to symptomatic patients while giving 1
      unit at a time. Further prospective studies will be needed to confirm these
      results.

PMID- 24100586
TI  - Novel tools to dissect the dynamic regulation of TCR signaling by the kinase Csk
      and the phosphatase CD45.
AB  - Although the biochemical events induced by T-cell receptor (TCR) triggering have
      been well studied, both the mediators and function of basal signaling in T cells
      remain poorly understood. Furthermore, the precise mechanisms by which MHC
      peptide interaction with the TCR disrupt the basal equilibrium to induce
      downstream signaling are also unclear. Here we describe novel approaches to
      understand the basal state of T cells and the mechanisms of TCR triggering by
      perturbing regulation of the Src family kinases (SFKs). The SFKs are critical
      proximal mediators of TCR signaling that are in turn tightly regulated by the
      tyrosine kinase Csk and the receptor-like tyrosine phosphatase CD45. We have
      developed a small-molecule analog-sensitive allele of Csk and an allelic series
      of mice in which expression of CD45 is varied across a broad range. Our studies
      have unmasked contributions of Csk and CD45 to maintain the basal state of T
      cells and also suggest that dynamic regulation of Csk may be involved in TCR
      triggering. 

PMID- 24100589
TI  - Accuracy and reproducibility of the peritoneal cancer index in advanced ovarian
      cancer during laparoscopy and laparotomy.
AB  - BACKGROUND: The aim of this prospective study was to evaluate the accuracy of the
      peritoneal cancer index (PCI) between laparoscopy and laparotomy and to evaluate
      the reproducibility of this index between 2 surgeons (junior vs senior) in
      advanced-stage ovarian cancer (ASOC). In ASOC, the quality of cytoreductive
      surgery, which is the main prognostic factor, is correlated with the extent of
      the disease and thus with the PCI. The reliability of this scoring index between
      different surgeons during laparoscopy and laparotomy has not been investigated in
      this disease. METHODS: Between April 2010 and October 2011, for each of the 29
      patients undergoing complete cytoreductive surgery, 1 senior surgeon and 1 junior
      surgeon quantified the PCI score at 3 time points on the same day: during
      laparoscopy and during laparotomy, at the beginning and at the end. A concordance
      analysis was conducted with Bland and Altman's method and estimated by intraclass
      correlation coefficients. RESULTS: There was high concordance of the PCI score
      between the junior and senior surgeons during the laparoscopic and laparotomic
      procedures: the mean differences were not significantly different from 0 (P <
      0.05) and 95% limits of agreement were +/- 3.5 and +/- 3.0, respectively.
      Laparoscopy underestimated the PCI score by approximately 2 points compared to
      the beginning of the laparotomy: the mean biases were -2.0 (95% confidence
      interval, -2.8 to -1.2) for the senior surgeon and -2.2 (95% confidence interval,
      -3.1 to 1.3) for the junior surgeon. CONCLUSIONS: The PCI is reproducible and
      reliable for evaluating peritoneal spread in ASOC.

PMID- 24100590
TI  - Platinum-based neoadjuvant chemotherapy followed by radical surgery for cervical
      carcinoma international federation of gynecology and obstetrics stage IB2-IIB.
AB  - OBJECTIVE: The objective of this study was to determine the response rate to
      chemotherapy, as well as the progression-free survival (PFS), the overall
      survival (OS), and the main prognostic factors in patients treated at the
      European Institute of Oncology in Milan, Italy. METHODS: Retrospective data were
      collected on patients with uterine cervical carcinoma, International Federation
      of Gynecology and Obstetrics (FIGO) stage IB2 to IIB, who underwent platinum
      based neoadjuvant chemotherapy (NACT) followed by radical hysterectomy. RESULTS:
      A total of 121 patients were studied. The median (range) age was 45 years old (23
      69 years). The distribution of patients by International Federation of Gynecology
      and Obstetrics stage was as follows: n = 88 (73%) with stage IB2, n = 7 (6%) with
      stage IIA, and n = 26 (21%) with stage IIB. The median (range) tumor size was 50
      mm (20-90 mm). Neoadjuvant chemotherapy involved a combination of cisplatin,
      paclitaxel, and ifosfamide in 80 patients (65%). Using this treatment, 112
      patients (93%) received 3 cycles of NACT, whereas 6 (5%) received 4 cycles.
      Complete and partial pathology response was observed in 9 patients (7%) and 79
      patients (66%), respectively. Adjuvant radiotherapy was not necessary in 65% of
      patients. A 5-year PFS and OS of 58% and 71%, respectively, were observed.
      Independent prognostic factors for PFS and OS were identified, including response
      to NACT, persistent lymph node metastases, and parametrial involvement.
      CONCLUSIONS: Neoadjuvant chemotherapy in this group of tumors is a promising
      treatment strategy and should be discussed with patients. Although these results
      are comparable to those obtained by standard chemoradiation treatment, one
      strategy should not be recommended over the other until the results of the
      ongoing phase 3 trial for NACT are released.

PMID- 24100591
TI  - A patient with a paced rhythm presenting with chest pain and hypotension.

PMID- 24100593
TI  - Predictability of the Ningaloo Nino/Nina.
AB  - The seasonal prediction of the coastal oceanic warm event off West Australia,
      recently named the Ningaloo Nino, is explored by use of a state-of-the-art ocean
      atmosphere coupled general circulation model. The Ningaloo Nino/Nina, which
      generally matures in austral summer, is found to be predictable two seasons
      ahead. In particular, the unprecedented extreme warm event in February 2011 was
      successfully predicted 9 months in advance. The successful prediction of the
      Ningaloo Nino is mainly due to the high prediction skill of La Nina in the
      Pacific. However, the model deficiency to underestimate its early evolution and
      peak amplitude needs to be improved. Since the Ningaloo Nino/Nina has potential
      impacts on regional societies and industries through extreme events, the present
      success of its prediction may encourage development of its early warning system. 

PMID- 24100592
TI  - Interleukin-4 deficiency protects mice from acetaminophen-induced liver injury
      and inflammation by prevention of glutathione depletion.
AB  - OBJECTIVE: Interleukin-4 (IL-4) is a multifunctional cytokine involved in many
      diseases such as autoimmune hepatitis and idiosyncratic drug reactions. However,
      its role in acetaminophen (APAP)-induced liver injury remains unclear. Our
      objective was to evaluate the contribution of IL-4 to the pathogenesis of APAP
      induced liver injury. METHODS: Balb/C (WT) and IL-4 knockout (IL-4(-/-)) mice
      were orally overdosed with APAP. After 24 h, survival percentage, biochemical and
      morphological markers of liver injury, and tissue inflammation were assessed.
      RESULTS: IL-4(-/-) mice were protected from APAP toxicity. Intravital confocal
      microscopy, tissue histology and serum ALT levels showed significantly less liver
      injury and inflammation than in the WT group, which may explain the increased
      survival rate of IL-4(-/-) mice. In addition, IL-4(-/-) mice had decreased
      production of tumor necrosis factor alpha, CXCL1 and interleukin-1beta in the
      liver, but not in a remote site such as the lungs. Hepatic macrophage activation
      was markedly reduced in IL-4-deficient mice. In addition, glutathione depletion-a
      primary cause of APAP-mediated injury-was significantly attenuated in IL-4(-/-)
      mice. CONCLUSIONS: Taken together, our data demonstrate that IL-4(-/-) mice are
      protected from APAP-induced liver injury due to reduced depletion of glutathione,
      which prevented liver damage and tissue inflammation.

PMID- 24100594
TI  - Clinical significance of stanniocalcin 2 expression as a predictor of tumor
      progression in gastric cancer.
AB  - Stanniocalcin 2 (STC2) is a glycoprotein hormone that plays an important role in
      calcium and phosphate homeostasis. Furthermore, recent studies have demonstrated
      that STC2 expression in the primary site is correlated with tumor progression in
      several types of malignancies. However, few reports have investigated the
      clinical significance of STC2 expression in the blood of patients with gastric
      cancer. Therefore, we examined STC2 expression as a molecular blood marker for
      detection of circulating tumor cells (CTCs) and assessed the relationship between
      STC2 expression and clinico-pathological features including prognosis in patients
      with gastric cancer. Quantitative PCR assay was used to assess STC2 mRNA
      expression in 4 gastric cancer cell lines and in blood specimens from 93 patients
      with gastric cancer and 22 healthy volunteers. The numbers of STC2 mRNA copies
      were significantly higher in the gastric cancer cell lines and in blood from
      patients with gastric cancer than in blood from healthy volunteers (P=0.0002 and
      P=0.01, respectively). STC2 expression was positive in 43 (46.2%) of the 93
      patients with gastric cancer, and its expression was significantly correlated
      with age, depth of tumor invasion, lymph node metastasis, stage and venous
      invasion (P=0.023, P=0.045, P=0.035, P=0.007 and P=0.027, respectively). The 5
      year survival rate was significantly lower in patients with STC2 expression
      compared to patients without STC2 expression (P=0.014). Our results indicate that
      STC2 could be a useful molecular blood marker for predicting tumor progression by
      monitoring CTCs in patients with gastric cancer.

PMID- 24100595
TI  - A new ditopic Gd(III) complex functionalized with an adamantyl moiety as a
      versatile building block for the preparation of supramolecular assemblies.
AB  - A dimeric GdAAZTA-like complex (AAZTA is 6-amino-6-methylperhydro-1,4
      diazepinetetraacetic acid) bearing an adamantyl group (Gd2L1) able to form strong
      supramolecular adducts with specific hosts such as beta-cyclodextrin (beta-CD),
      poly-beta-CD, and human serum albumin (HSA) is reported. The relaxometric
      properties of Gd2L1 were investigated in aqueous solution by measuring the (1)H
      relaxivity as a function of pH, temperature, and magnetic field strength. The
      relaxivity of Gd2L1 (per Gd atom) at 40 MHz and 298 K is 17.6 mM(-1) s(-1), a
      value that remains almost constant at higher fields owing to the great
      compactness and rigidity of the bimetallic chelate, resulting in an ideal value
      for the rotational correlation time for high-field MRI applications (1.5-3.0 T).
      The noncovalent interaction of Gd2L1 with beta-CD, poly-beta-CD, and HSA and the
      relaxometric properties of the resulting host-guest adducts were investigated
      using (1)H relaxometric methods. Relaxivity enhancements of 29 and 108 % were
      found for Gd2L1-beta-CD and Gd2L1-poly-beta-CD, respectively. Binding of Gd2L1 to
      HSA (KA = 1.2 * 10(4) M(-1)) results in a remarkable relaxivity of 41.4 mM(-1) s(
      1) for the bound form (+248 %). The relaxivity is only limited by the local
      rotation of the complex within the binding site, which decreases on passing from
      Gd2L1-beta-CD to Gd2L1-HSA. Finally, the applicability of Gd2L1 as tumor
      targeting agent through passive accumulation of the HSA-bound adduct was
      evaluated via acquisition of magnetic resonance images at 1 T of B16-tumor
      bearing mice. These experiments indicate a considerable signal enhancement (+160
      %) in tumor after 60 min from the injection and a very low hepatic accumulation.

PMID- 24100596
TI  - The role of lactation in GDM women.
AB  - Lactating women exhibit more favorable blood glucose and insulin profiles, as
      well as increased insulin sensitivity than nonlactating women. Yet, much less is
      known about whether these favorable effects on metabolic risk factors persist
      long-term among women with gestational diabetes mellitus (GDM). The evidence that
      lactation reduces incident type 2 diabetes after GDM pregnancy is limited and
      inconsistent. Well-controlled, prospective studies that measure lactation
      intensity and duration, and comprehensively screen for postpartum glucose
      tolerance are needed to conclusively determine whether lactation can lead to
      reduced risk of type 2 diabetes after GDM pregnancy. 

PMID- 24100597
TI  - Secondary osteoporosis: differential diagnosis and workup.
AB  - There are numerous causes of secondary osteoporosis including endocrine
      disorders, nutritional deficiencies, and other miscellaneous conditions and
      medications. It is essential to identify and address these factors to
      appropriately manage patients with osteoporosis. Failure to do so may result in
      further bone loss despite pharmacologic intervention for osteoporosis. The
      following diagnostic studies should be considered initially: complete blood
      count, complete metabolic panel, 25-hydroxyvitamin D level, testosterone level in
      men, and 24-hour urinary calcium, sodium, and creatinine. Further testing may be
      performed in selected patients depending on the clinical picture and results of
      the initial workup. 

PMID- 24100598
TI  - Osteoporosis treatment and prevention for postmenopausal women: current and
      future therapeutic options.
AB  - Osteoporosis, a "silent disease," is often unrecognized until fracture. Lifestyle
      modification with nutritional counseling is recommended during menopausal
      transition. Bone density testing is recommended for women aged 65 years and
      older, younger postmenopausal women with risk factors, or to follow therapy.
      Bisphosphonates treat osteoporosis (prevent bone resorption). Raloxifene and
      hormone therapy prevent bone loss and fracture, with extraskeletal benefits.
      Denosumab treats osteoporosis, although bone effects reverse rapidly.
      Teriparatide (anabolic therapy) is considered for women at high risk of fracture.
      Bazedoxifene with conjugated estrogens, novel delivery of teriparatide, new
      parathyroid hormone proteins, anti-sclerostin antibodies, cathepsin K inhibitors,
      and stem cell therapies are in testing. 

PMID- 24100599
TI  - Osteoporosis risk factors and early life-style modifications to decrease disease
      burden in women.
AB  - Prevention of osteoporosis should begin in childhood and continue throughout
      adulthood. Although genetic determinants of muscle and bone mass may offer other
      therapeutic options in the future, currently, counseling should primarily focus
      on lifestyle modification including healthy dietary practices and regular
      exercise. Vitamin supplementation, particularly vitamin D, should be considered
      to enhance diet based on patient's need. Attention to estrogen status is also
      important. In addition, patients should be counseled regularly about cigarette
      cessation and avoiding moderate alcohol intake. 

PMID- 24100600
TI  - Consumption of wheat bran modified by autoclaving reduces fat mass in hamsters.
AB  - PURPOSE: To investigate the effect that wheat bran modified by autoclaving (MWB)
      had on reducing fat accumulation in hamsters fed a hypercholesterolemia- and
      obesity-inducing diet. METHODS: Male hamsters (n = 45) were randomized into 3
      groups and fed a hypercholesterolemia- and obesity-inducing diet with or without
      10% standard wheat bran or MWB for 28 days. Our outcome measures included body
      composition measured by DXA, oxygen consumption and plasma lipids and glucose
      concentrations. RESULTS: Animals fed the MWB diet had lower % fat mass (49.8 vs.
      53.4%; p = 0.02) and higher % lean body mass (47.2 vs. 44.1%; p = 0.02) compared
      with controls despite no differences in food intake or weight gain. Additionally,
      plasma glucose tended to be lower (6.9 vs. 8.5 mmol/l; p < 0.08) in the MWB
      animals compared with controls. CONCLUSIONS: Our data suggest that the
      compositional changes in autoclaved wheat bran, specifically solubility of
      phenolic antioxidants and fiber, may have contributed to the lower fat
      accumulation in our animals. Further study is needed to determine whether the
      exact mechanism involved increased lipolysis and energy utilization from adipose.

PMID- 24100601
TI  - Long-term dietary L-arginine supplementation increases endothelial nitric oxide
      synthase and vasoactive intestinal peptide immunoexpression in rat small
      intestine.
AB  - BACKGROUND AND AIMS: Nitric oxide (NO) and vasoactive intestinal polypeptide
      (VIP) are important intestinal neurotransmitters that coexist in the gut enteric
      nervous system and play an important role in intestinal physiology (e.g.,
      absorption, motility, fluid secretion and smooth muscle relaxation). It is also
      known that cold exposure alters several aspects of gastrointestinal physiology
      and induces hyperphagia to meet increased metabolic demands, but there are no
      data regarding NO and VIP involvement in intestinal response during acclimation
      to cold. The objective of this study was to determine the influence of long-term
      L-arginine supplementation on the expression of the three isoforms of nitric
      oxide synthase (NOS) and VIP in small intestine of rats acclimated to room
      temperature or cold. METHODS: Animals (six per group) acclimated to room
      temperature (22 +/- 1  degrees C) and cold (4 +/- 1  degrees C), respectively,
      were treated with 2.25% L-arginine, a substrate for NOSs, or with 0.01% N(omega)
      nitro-L-arginine methyl ester, an inhibitor of NOSs, for 45 days. The
      topographical distribution of VIP and NOSs expression in small intestine was
      studied by immunohistochemistry, and ImageJ software was used for
      semiquantitative densitometric analysis of their immunoexpression. RESULTS: Long
      term dietary L-arginine supplementation increases VIP and NOSs immunoexpression
      at room temperature while at cold increases the endothelial NOS, inducible NOS
      and VIP but decrease neuronal NOS in rat small intestine. CONCLUSION: Our results
      demonstrate that long-term dietary L-arginine supplementation modulates NOSs and
      VIP immunoexpression in rat small intestine with respect to ambient temperature,
      pointing out the eNOS as a predominant NOS isoform with an immunoexpression
      pattern similar to VIP.

PMID- 24100603
TI  - Simultaneous improvements in power conversion efficiency and operational
      stability of polymer solar cells by interfacial engineering.
AB  - This article addresses simultaneous improvements in the photovoltaic performance
      and operational stability of organic photovoltaic devices (OPVs) in the inverted
      configuration when nanostructured ZnO characterized by a lower density of
      localized surface atomic energy states is employed as an electron transport
      layer. Two sets of devices with the configuration ITO/ZnO/P3HT:PCBM/MoO3/Ag are
      employed in the present study. A difference in the density of localized energy
      states in the band gap of ZnO was produced by altering the crystallinity by
      annealing the ZnO at two temperatures, viz. 160 and 240  degrees C. The devices
      are characterized by scanning electron microscopy, X-ray diffractometry, current
      voltage (I-V) measurements as functions of temperature and illumination
      intensity, incident photon to current conversion efficiency (IPCE) spectroscopy,
      and charge extraction by linearly increasing photovoltage (CELIV) spectroscopy.
      The devices fabricated using the ZnO nanostructures annealed at 240  degrees C
      have shown remarkably higher power conversion efficiency (PCE) and IPCE values
      than the other device. From I-V measured as a function of photon flux and
      temperature we show that the device with higher PCE is characterized by a lower
      depth of localized energy states by a factor of two than the other device. The
      implications of the lower trap depth was also evaluated using CELIV and the
      corresponding charge mobility obtained differed by a factor of three between the
      two sets of devices. The device with lower equilibrium concentration at the
      interface has three fold higher charge mobility and 40% enhanced photoconversion
      efficiency. The stability of the devices was evaluated with and without
      encapsulation under simulated sunlight (AM 1.5) following the ISOS-D-1 (shelf)
      and the ISOS-L-1 protocols; the device with higher PCE also showed higher
      operational stability. The findings in this study are expected to provide new
      directions in fabricating organic-inorganic heterojunction devices with high
      performance and stability. 

PMID- 24100602
TI  - A novel resveratrol analogue, HS-1793, inhibits hypoxia-induced HIF-1alpha and
      VEGF expression, and migration in human prostate cancer cells.
AB  - In many studies, resveratrol has been shown to have a chemopreventive effect in
      various types of cancer cells. However, the biological activity of resveratrol is
      limited by its photosensitivity and metabolic instability. This study
      investigated the effects of a novel analogue of resveratrol, HS-1793, on the
      expression of HIF-1alpha and vascular endothelial growth factor (VEGF) in PC-3
      human prostate cancer cells. Hypoxic condition induced HIF-1alpha protein level
      in PC-3 cells in a time-dependent manner, and treatment with HS-1793 markedly
      decreased HIF-1alpha expression levels. HS-1793 also inhibited VEGF level.
      Mechanistically, HS-1793 inhibited HIF-1alpha and VEGF expression through
      multiple mechanisms. Firstly, HS-1793 inhibited phosphorylation of PI3K and Akt
      in PC-3 cells. Furthermore, HS-1793 substantially induced HIF-1alpha protein
      degradation through the proteasome pathway. Finally, HS-1793 inhibited hypoxia
      induced PC-3 cell migration. These data suggest that HS-1793 may inhibit human
      prostate cancer progression and angiogenesis by inhibiting the expression of HIF
      1alpha and VEGF. Moreover, HS-1793 showed more potent effects than resveratrol on
      the cytotoxic effects on PC-3 cells. Taken together, these results implied that
      HS-1793, a novel analogue of resveratrol, may be a new potent chemopreventive
      agent against human prostate cancer cells.

PMID- 24100604
TI  - Knockdown and larvicidal activity of six monoterpenes against Aedes aegypti
      (Diptera: Culicidae) and their structure-activity relationships.
AB  - The relationships between physicochemical parameters of majority components of
      Eucalyptus essential oils and their insecticide effect were evaluated on Aedes
      aegypti (L.) (Diptera: Culicidae). The octanol-water partition coefficients of
      the monoterpenes were estimated by the atom/fragment contribution method and the
      vapor pressures were determined by our laboratory in previous studies. The
      larvicidal activity (LC50 (ppm)) and knockdown effect (KT50 (min)) of each
      component was determined. The results show that the toxicity of EOs main
      components of Eucalyptus on adults and larvae of A. aegypti is strongly related
      to their physicochemical properties (vapor pressure and Log P). However, the
      interaction of both variables (vapor pressure * Log P) explains the toxicological
      phenomenon more precisely. The regression models were expressed as follows: KT
      50(min) =  - 10.9 + 3.7 * Log P + 1.9 * 1/Pvapor (R(2) = 0.80; F = 42.5) and LC
      50(ppm) =  - 94.3 + 438.6 *  1/Log P + 2.8 *  1/Pvapor (F = 57.8; R(2) = 0.85).
      The six evaluated components present different functional groups. Therefore, it
      was considered to evaluate the monoterpenes as a group and separated in two
      groups: oxygenated monoterpenes (alpha-terpineol, 4-terpineol, and 1,8-cineole)
      and terpene hydrocarbons (gamma-terpinene, p-cymene, and alpha-pinene). The
      results show the regression models for each group as follows: (A) oxygenated
      terpenes: KT 50(min) = - 515.3 + 1613.2 * 1/Log P + 5, 2 * 1/Pvapor (F = 3176.7
      R(2) = 0.99) and LC 50(ppm)  =  - 1679.4 + 5402.1 * 1/Log P + 12.7 *  1/Pvapor (F
      = 282.9; R(2) = 0.99). (B) Hydrocarbons terpenes: KT 50(min) = 18.2 - 58.3 *
      1/Log P + 2.7 * 1/Pvapor (F = 171.7;  R(2) = 0.97) and LC 50(ppm) = - 21.1 +
      174.9 * 1/Log P - 14.3 * 1/Pvapor (F = 410.0; R(2) = 0.99). The association
      between the toxic effect of the evaluated monoterpenes against A. aegypti and the
      physicochemical properties can be better described when they are separated into
      functional groups (hydrocarbons vs. oxygenated terpenes).

PMID- 24100605
TI  - Identification and characterization of the second cysteine protease inhibitor of
      Clonorchis sinensis (CsStefin-2).
AB  - CsStefin-2, the second cysteine protease inhibitor of Clonorchis sinensis, was
      identified and characterized. CsStefin-2 is a cysteine protease inhibitor that
      belongs to family 1 stefins based on its phylogenetic and structural properties.
      However, CsStefin-2 had a QIVSG cystatin motif distinct from the common QVVAG
      cystatin motif that is well conserved in family 1 stefins. Mutagenesis analysis
      revealed that the two amino acid substitutions in the QIVSG cystatin motif of
      CsStefin-2 did not affect its inhibitory activity. Molecular modeling also
      indicated that no critical change was induced in the interaction between CsStefin
      2 and its target enzyme. CsStefin-2 showed broad inhibitory activities against
      several cysteine proteases, including human cathepsins B and L, papain, and
      cathepsin Fs of C. sinensis (CsCFs), and effectively inhibited the autocatalytic
      maturation of CsCF-6. Native CsStefin-2 was assembled into a homo-tetramer, in
      which intermolecular disulfide bonds are not involved in the assembly of the
      tetramer. CsStefin-2 was expressed throughout the various developmental stages of
      the parasite and was localized in the intestinal epithelium, where CsCFs are
      actively synthesized. These results suggest that CsStefin-2 is the second active
      cysteine protease inhibitor of C. sinensis that shares functional redundancy with
      CsStefin-1 to modulate the activity and processing of CsCFs. 

PMID- 24100606
TI  - Occurrence of gastrointestinal parasites in slaughter rabbits.
AB  - The aim of the study was to determine the occurrence of gastrointestinal
      parasites in slaughter rabbits managed in small scale farms and under industrial
      farming system. The research material included intestines and livers of rabbits
      slaughtered between years 2007 and 2011. The rabbit carcasses submitted to
      parasitological examination had passed the sanitary veterinary inspection as fit
      for human consumption. The samples were collected in spring and autumn seasons.
      The studies showed no effect of a rabbit farming system, season of the year, or
      differences in an invasion type in each year. The parasitological test recognized
      exclusively mixed infestation diagnosed in 79.56% of the studied animals.
      Parasitological evaluation of the rabbit internal organs identified the invasions
      of coccidia (78.83%), nematoda (16.42%), cestoda (0.72%), and cysticerci
      Cysticercus pisiformis (4.74%). Coccidian invasions found in intestines were
      dominant, and their prevalence reached 56.48%, while the hepatic coccidian
      extensity was markedly lower, i.e., 3.34% of the examined rabbits. Invasions were
      characterized by low intensity. The studies recognized invasions of nematoda
      (Obeliscoides cuniculi, Graphidium strigosum, Trichostrongylus sp., Strongyloides
      sp., Passalurus ambiguus, Trichuris leporis), cestoda (Mosgovoyia pectinata), and
      cysticerci C. pisiformis.

PMID- 24100607
TI  - Morphology and 18S rDNA sequencing identifies Henneguya visibilis n. sp., a
      parasite of Leporinus obtusidens from Mogi Guacu River, Brazil.
AB  - During a survey of myxozoan parasites of freshwater fish from the Mogi Guacu
      River in Sao Paulo State, Brazil, plasmodia of Henneguya visibilis n. sp. were
      found on the fins of Leporinus obtusidens (Characiformes: Anostomidae). The
      plasmodia, which were observed on five out of eight (62.5%) L. obtusidens
      examined, were 400-1,000 MUm long. Mature spores were elongated with a spore body
      10.8 +/- 0.6 MUm long and 3.9 +/- 0.2 MUm wide, a caudal process 18 +/- 1.2 MUm
      long, and a total spore length of 26.8 +/- 1.1 MUm. Polar capsules were elongated
      4.9 +/- 0.3 MUm long and 1.4 +/- 0.1 MUm wide. Histological examination indicated
      that the plasmodia developed in the connective tissue, and no inflammatory
      infiltrate was observed at the infection site. Ultrastructural analysis showed a
      plasmodium wall with a single membrane and several pinocytotic canals.
      Sporogenesis occurred from the periphery to the center of the plasmodia.
      Phylogenetic analysis of the 18S rDNA sequence using maximum likelihood and
      maximum parsimony methods showed H. visibilis n. sp. positioned in a sub-clade
      composed of Henneguya/Myxobolus parasites of several freshwater fish families.

PMID- 24100609
TI  - Single-molecule photophysics of dark quenchers as non-fluorescent FRET acceptors.
AB  - Dark quencher chromophores are interesting alternatives to common single-molecule
      FRET acceptors. Due to their short excited state lifetime, they should be less
      prone to complex photophysics and bleaching. We find, however, that for common
      enzymatic oxygen scavenging systems and photoprotection strategies - the gold
      standard of single-molecule measurements - the quenchers BBQ650 and BHQ-2 induce
      frequent blinking of the donor molecule. They switch in a photoinduced process to
      what we identify as a radical anion state and back. We further make use of the
      broad absorption spectrum for selective bleaching of the quenchers in order to
      photoactivate the fluorescence of initially completely quenched dye molecules.
      This represents a general strategy to turn fluorescent dyes into photoactivatable
      probes. 

PMID- 24100608
TI  - Probing cell traction forces in confined microenvironments.
AB  - Cells migrate in vivo within three-dimensional (3D) extracellular matrices. Cells
      also migrate through 3D longitudinal channels formed between the connective
      tissue and the basement membrane of muscle, nerve, and epithelium. Although
      traction forces have been measured during 2D cell migration, no assay has been
      developed to probe forces during migration through confined microenvironments. We
      thus fabricated a novel microfluidic device consisting of deflectable PDMS
      microposts incorporated within microchannels of varying cross-sectional areas.
      Using NIH-3T3 fibroblasts and human osteosarcoma (HOS) cells as models, we found
      that the average traction forces per post decreased upon increasing confinement.
      Inhibition of myosin-II function by blebbistatin in HOS cells decreased traction
      forces in unconfined (wide) channels but failed to alter them in confined spaces.
      Myosin activation by calyculin A also failed to affect traction forces in
      confining channels but increased them in wide channels. These observations
      underlie the importance of the physical microenvironment in the regulation of
      cell migration and cellular traction forces. 

PMID- 24100610
TI  - Deregulation of let-7e in epithelial ovarian cancer promotes the development of
      resistance to cisplatin.
AB  - Drug resistance remains a major clinical obstacle to successful treatment in
      ovarian cancer patients, and the evidence of microRNAs involvement in drug
      resistance has been emerging recently. In this report, we investigated the role
      of let-7e in the development of cisplatin-resistant ovarian cancer. On the
      cellular level, let-7e expression was significantly reduced in cisplatin
      resistant human epithelial ovarian cancer (EOC) cell line A2780/CP compared with
      parental A2780 cell and decreased in a concentration-dependent manner in A2780,
      SKOV3 and ES2 cells treated with cisplatin. Overexpression of let-7e by
      transfection of agomir could resensitize A2780/CP and reduce the expression of
      cisplatin-resistant-related proteins enhancer of zeste 2 (EZH2) and cyclin D1
      (CCND1), whereas let-7e inhibitors increased resistance to cisplatin in parental
      A2780 cells. Quantitative methylation-specific PCR analysis showed
      hypermethylation of the CpG island adjacent to let-7e in A2780/CP cells, and
      demethylation treatment with 5-aza-CdR or transfection of pYr-let-7e-shRNA
      plasmid containing unmethylated let-7e DNA sequence could restore let-7e
      expression and partly reduce the chemoresistance. In addition, cisplatin combined
      with let-7e agomirs inhibited the growth of A2780/CP xenograft more effectively
      than cisplatin alone. Diminished expression of EZH2 and CCND1 and higher
      cisplatin concentrations in tumor tissue of mice subjected to administration of
      let-7e agomirs in addition to cisplatin were revealed by immunohistochemistry and
      atomic absorption spectroscopy, respectively. Taken together, our findings
      suggest that let-7e may act as a promising therapeutic target for improvement of
      the sensibility to cisplatin in EOC. 

PMID- 24100611
TI  - Knockdown of RON receptor kinase delays but does not prevent tumor progression
      while enhancing HGF/MET signaling in pancreatic cancer cell lines.
AB  - In this study, the role of RON (receptor originated from nantes) in tumor
      progression was further investigated in context with MET expression and activity.
      RON and MET expressions were not detected in an immortalized normal human
      pancreas cell line (HPNE), but were co-expressed in five of seven pancreatic
      ductal adenocarcinoma (PDAC) cell lines (PANC-1, BxPC-3, Capan-2, CFPAC-1 and
      AsPC-1). RON expression was knocked down by an shRNA approach in two PDAC cell
      lines (BxPC-3 and CFPAC-1) that co-express MET. Knockdown of RON significantly
      inhibited cell growth, clonogenicity and macrophage stimulating protein (MSP),
      RON ligand induced invasion by in vitro assays and significantly inhibited tumor
      growth (P<0.001) and metastasis (P<0.009) in an orthotopic pancreatic cancer
      mouse model at week 7. However, by week 9, the mice implanted with RON knockdown
      cells had developed similar size primary tumors and metastases compared with that
      seen in the control group at week 7. Western blotting and immunohistochemistry
      analyses showed that MET remains highly expressed in cells and tumor tissues
      where RON was knocked down. Moreover, knockdown of RON did not prevent hepatocyte
      growth factor (HGF) stimulated invasion in in vitro Matrigel assays. Treating
      cells with MSP induced the transphosphorylation of MET, suggesting that signaling
      may be modulated by relative levels of RON and MET receptors and their
      corresponding ligands. To this point, HGF treatment of RON knockdown cells caused
      an increase in intensity and duration of MET signaling, suggesting that MET
      signaling may compensate for loss of RON signaling. Treatment of cells with an
      MET inhibitor, PHA-665752, had minimal effects on inhibiting cell growth but
      significantly inhibited cell invasion induce by ligands for either MET or RON.
      These results suggest that HGF/MET signaling may have a more important role in
      tumor cell invasion and metastasis rather than in tumor cell proliferation. This
      study indicates that specific inhibition of RON delays but does not prevent
      progression of PDAC. Moreover, specific signaling may be modulated by the
      interaction of RON and MET receptors. This dynamic interaction of RON and MET in
      pancreatic cancer cells suggests that dual targeting of both RON and MET will be
      preferable to inhibition of either target alone. 

PMID- 24100612
TI  - Blood volatile compounds as biomarkers for colorectal cancer.
AB  - Many recent studies have focused on the connection between the composition of
      specific volatile organic compounds (VOCs) in exhaled breath and various forms of
      cancer. However, the composition of exhaled breath is affected by many factors,
      such as lung disease, smoking, and diet. VOCs are released into the bloodstream
      before they are exhaled; therefore, the analysis of VOCs in blood will provide
      more accurate results than the analysis of VOCs in exhaled breath. Blood were
      collected from 16 colorectal cancer patients and 20 healthy controls, then solid
      phase microextraction-chromatography-mass spectrometry (SPME-GC-MS) was used to
      analysis the exhaled volatile organic compounds (VOCs). The statistical methods
      principal component analysis (PCA) and partial least-squares discriminant
      analysis (PLSDA) were performed to deal with the final dates. Three metabolic
      biomarkers were found at significantly lower levels in the group of CRC patients
      than in the normal control group (P<0.01): phenyl methylcarbamate, ethylhexanol,
      and 6-t-butyl-2,2,9,9-tetramethyl-3,5-decadien-7-yne. In addition, significantly
      higher levels of 1,1,4,4-tetramethyl-2,5-dimethylene-cyclohexane were found in
      the group of CRC patients than in the normal control group (P<0.05). Compared
      with healthy individuals, patients with colorectal adenocarcinoma exhibited a
      distinct blood metabolic profile with respect to VOCs. The analysis of blood VOCs
      appears to have potential clinical applications for CRC screening. 

PMID- 24100613
TI  - TGF-beta-induced miR10a/b expression promotes human glioma cell migration by
      targeting PTEN.
AB  - Human gliomas are associated with high rates of morbidity and mortality. In the
      brain, increased mRNA levels of transforming growth factor beta (TGF-beta)
      correlate with the degree of malignancy of human gliomas. miR10a/10b expression
      has been demonstrated to be associated with TGF-beta expression in brain tumors,
      and it is reported that TGF-beta induces miR10 expression. Therefore, miR10a/10b
      expression may be induced by TGF-beta expression and may be involved in the TGF
      beta-induced migration of brain tumor cells. The present study examined the
      expression of TGF-beta and miR10a/10b in the tissues of 10 patients with brain
      tumors using quantitative PCR (qPCR), and the correlation between TGF-beta and
      miR10a or miR10b expression was analyzed. Additionally, U251 and SHG-44 cells
      were treated with TGF-beta and the expression of miR10a/10b was examined.
      Further, cell migration was analyzed following transfection of U251 cells with
      miR10a/10b and the association between miR10a/10b and phosphatase and tensin
      homolog deleted on chromosome 10 (PTEN) was investigated. U251 cells were
      transfected with miR10a/10b inhibitors and a PTEN expression plasmid prior to TGF
      beta treatment and then cell migration was assessed. A significant correlation
      was identified between TGF-beta and miR10a expression (r2=0.6936, P=0.007) and
      between TGF-beta and miR10b expression (r2=0.5876, P=0.02) in the tissues of
      patients with brain tumors. The results also showed that TGF-beta induces
      miR10a/10b expression and that TGF-beta-induced miR10a/10b expression promotes
      cell migration through the suppression of PTEN. In conclusion, TGF-beta-induced
      miR10a/10b promotes brain tumor migration. This study may provide a number of
      suggestions for the clinical treatment of brain tumors.

PMID- 24100614
TI  - Rapid evaluation of chest pain in the emergency department.

PMID- 24100615
TI  - Chemical and biological detection.

PMID- 24100616
TI  - Arg-Thz is a minimal substrate for the N(alpha),N(alpha)-arginyl
      methyltransferase involved in the biosynthesis of plantazolicin.
AB  - The final biosynthetic step towards plantazolicin (PZN) comprises
      N(alpha),N(alpha)-arginyl methyltransferase (PznL) mediated N-terminal
      bismethylation. We show that PznL processes truncated desmethyl-plantazolicin
      analogues, but only those with an N-terminal guanidine side chain derived from
      arginine. PznL specificity, which is narrow, depends on the side chain of the N
      terminal amino acid linked to an azole, and not so much on the number of azoles. 

PMID- 24100617
TI  - Genetic modulation of personality traits: a systematic review of the literature.
AB  - The heritability of human personality traits is by now well established. However,
      since the first reports on associations between specific genetic variants and
      personality traits, only modest progress has been made in identifying loci that
      robustly support these associations. The aim of this study was to provide a
      summary of literature data on association studies focused on the genetic
      modulation of personality, according to the Cloninger, Eysenck and Costa and
      McCrae models. PubMed was searched for papers investigating the association
      between any gene variant and personality traits, which were grouped into five
      clusters: (a) anxiety, (b) impulsivity, (c) determination-activity, (d)
      socialization and (e) spirituality, in healthy individuals, populations and
      psychiatric patients. A total of 369 studies were included. No clear consensus on
      the role of any individual gene variant in personality modulation emerged,
      although SLC6A4 haplotypes and the DRD4 rs1800955 promoter variant seemed to be
      more reliably related to anxiety and impulsivity-related traits, respectively.
      Because conflicting results emerged from the literature, plausibly as a result of
      the combined influence of many loci of small effects on personality, larger
      sample sizes and more narrow and specific phenotype will be the minimum
      requirements for future genetic studies on personality. Moreover, gene * gene and
      gene * environment interaction studies deserve further attention.

PMID- 24100618
TI  - Screening for dementia in general hospital inpatients: a systematic review and
      meta-analysis of available instruments.
AB  - OBJECTIVE: Dementia is common and often undiagnosed. Improving rates of diagnosis
      has become a key part of current dementia guidelines. Older people admitted to
      hospital are a potential target population for screening for dementia. The
      objective was to report whether instruments advocated in screening for dementia
      had been validated in hospital inpatients and to make recommendations on evidence
      based screening for dementia in this population. DESIGN: a systematic review was
      performed by an initial electronic database search using three key search
      criteria. Studies were then selected in a systematic fashion using specific
      predetermined criteria. Pooled meta-analysis was performed. Inclusion criteria
      were studies where the study group were inpatients in general hospitals,
      including a clearly defined group of older people (60 or older), they used a
      recognised screening instrument compared with a reference standard, and included
      at least 10 cases of dementia. Demographic data as well as sensitivity and
      specificity were recorded from the selected studies. RESULTS: in total nine
      studies describing validation of six discreet instruments satisfied all our
      criteria and we were able to perform meta-analysis with one instrument, the
      Abbreviated Mental Test Score (AMTS). With a cut-off of <7, pooled analysis of
      the AMTS showed a sensitivity of 81%, a specificity of 84% and an area under the
      curve (AUC) of 0.88. CONCLUSION: a small number of instruments have been
      validated for screening for dementia in general hospital. Understanding strengths
      and weaknesses of currently available instruments allows informed decisions about
      screening in this setting.

PMID- 24100619
TI  - Which factors are associated with fear of falling in community-dwelling older
      people?
AB  - BACKGROUND: fear of falling (FOF) is common in older people and associated with
      serious physical and psychosocial consequences. Identifying those at risk of FOF
      can help target interventions to both prevent falls and reduce FOF. OBJECTIVE: to
      identify factors associated with FOF. STUDY DESIGN: cross-sectional study in
      1,088 community-dwelling older people aged >=65 years. METHODS: data were
      collected on socio-demographic characteristics, self-perceived health, exercise,
      risk factors for falls, FOF (Short FES-I), and functional measures. Logistic
      regression models of increasing complexity identified factors associated with
      FOF. RESULTS: high FOF (Short FES-I >=11) was reported by 19%. A simpler model
      (socio-demographic + falls risk factors) correctly classified as many
      observations (82%) as a more complex model (socio-demographic + falls risk
      factors + functional measures) with similar sensitivity and specificity values in
      both models. There were significantly raised odds of FOF in the simpler model
      with the following factors: unable to rise from a chair of knee height (OR:
      7.39), lower household income (OR: 4.58), using a walking aid (OR: 4.32),
      difficulty in using public transport (OR: 4.02), poorer physical health (OR:
      2.85), black/minority ethnic group (OR: 2.42), self-reported balance problems
      (OR: 2.17), lower educational level (OR: 2.01) and a higher BMI (OR: 1.06).
      CONCLUSIONS: a range of factors identify those with FOF. A simpler model performs
      as well as a more complex model containing functional assessments and could be
      used in primary care to identify those at risk of FOF, who could benefit from
      falls prevention interventions.

PMID- 24100620
TI  - [Ventricular tachycardia under stress : Characteristic symptom or prognostic
      relevance?].
AB  - Exercise-induced ventricular tachycardia (EIVT) is typical and quite common in
      patients with long QT-Syndrome (LQTS) or catecholaminergic polymorphic
      ventricular tachycardia (CPVT). Although patients with arrhythmogenic right
      ventricular cardiomyopathy (ARVC) or hypertrophic cardiomyopathy (HCM) experience
      EIVT infrequently, the occurrence of EIVT is of great prognostic value in these
      patients. The following overview will introduce these cardiomyopathies and
      highlight the importance of their EIVT.

PMID- 24100621
TI  - [Brugada syndrome].
AB  - Brugada syndrome is an ion channel disease which is associated with an increased
      risk of sudden cardiac death. Most probably the pathogenesis of ventricular
      fibrillation in these patients is a combination of both genetically determined
      repolarisation abnormalities and conduction delay in the right ventricular
      epicardium. The highest risk of sudden cardiac death is present in patients who
      have experienced syncope before, who reveal the pathognomic electrocardiographic
      changes already at rest and who have inducible ventricular fibrillation.
      Asymptomatic patients who have the J point elevations only after administration
      of a sodium channel blocker seem to be at lower risk. Most recently the latest
      joint consensus recommendations of the largest societies for diagnostic criteria,
      indications for genetic testing and therapy have been published. 

PMID- 24100622
TI  - Transcriptomic analysis of genes modulated by cyclo(L-phenylalanine-L-proline) in
      Vibrio vulnificus.
AB  - Diketopiperazine is produced by various organisms, including bacteria, fungi, and
      animals, and has been suggested as a novel signal molecule involved in the
      modulation of genes with various biological functions. Vibrio vulnificus, which
      causes septicemia in humans, produces cyclo(L-phenylalanine-L-proline) (cFP). To
      understand the biological roles of cFP, the effect of the compound on the
      expression of the total mRNA in V. vulnificus was assessed by nextgeneration
      sequencing. Based on the transcriptomic analysis, we classified the cFP-regulated
      genes into functional categories and clustered them according to the expression
      patterns resulted from treatment with cFP. From a total of 4,673 genes, excepting
      the genes encoding tRNA in V. vulnificus, 356 genes were up-regulated and 602
      genes were down-regulated with an RPKM (reads per kilobase per million) value
      above 3. The genes most highly induced by cFP comprised those associated with the
      transport and metabolism of inorganic molecules, particularly iron. The genes
      negatively regulated by cFP included those associated with energy production and
      conversion, as well as carbohydrate metabolism. Noticeably, numerous genes
      related with biofilm formation were modulated by cFP. We demonstrated that cFP
      interferes significantly with the biofilm formation of V. vulnificus. 

PMID- 24100623
TI  - SIRT1 suppresses activating transcription factor 4 (ATF4) expression in response
      to proteasome inhibition.
AB  - The synthetic machinery of ATF4 (activating transcription factor 4) is activated
      in response to various stress conditions involved in nutrient restriction,
      endoplasmic reticulum homeostasis, and oxidation. Stress-induced inhibition of
      proteasome activity triggers the unfolded protein response and endoplasmic
      reticulum stress, where ATF4 is crucial for consequent biological events. In the
      current study, we showed that the NAD(+)-dependent deacetylase, SIRT1, suppresses
      ATF4 synthesis during proteasome inhibition. SIRT1 depletion via transfection of
      specific siRNA into HeLa cells resulted in a significant increase in ATF4
      protein, which was observed specifically in the presence of the proteasome
      inhibitor MG132. Consistent with SIRT1 depletion data, transient transfection of
      cells with SIRT1-overexpressing plasmid induced a decrease in the ATF4 protein
      level in the presence of MG132. Interestingly, however, ATF4 mRNA was not
      affected by SIRT1, even in the presence of MG132, indicating that SIRT1-induced
      suppression of ATF4 synthesis occurs under post-transcriptional control.
      Accordingly, we propose that SIRT1 serves as a negative regulator of ATF4 protein
      synthesis at the post-transcriptional level, which is observed during stress
      conditions, such as proteasome inhibition. 

PMID- 24100624
TI  - Gibberellin production by newly isolated strain Leifsonia soli SE134 and its
      potential to promote plant growth.
AB  - Very few plant growth-promoting rhizobacteria (PGPR) are known to produce
      gibberellins (GAs). The current study aimed to isolate a phytohormone-producing
      PGP rhizobacterium from soil and assess its potential to enhance plant growth.
      The newly isolated bacterium was identified as Leifsonia soli sp. SE134 on the
      basis of partial 16S ribosomal RNA gene sequence. Application of L. soli culture
      filtrate significantly increased the biomass, hypocotyl, and root lengths of
      cucumber seeds as compared with non-inoculated sole medium and distilled water
      treated controls. Furthermore, the PGPR culture was applied to the GA-deficient
      mutant rice cultivar Waito-C. Treatment with L. soli SE134 significantly
      increased the growth of Waito-C rice seedlings as compared with controls. Upon
      chromatographic analysis of L. soli culture, we isolated, detected and quantified
      different GAs; namely, GA1 (0.61 +/- 0.15), GA4 (1.58 +/- 0.26), GA7 (0.54 +/-
      0.18), GA8 (0.98 +/- 0.15), GA9 (0.45 +/- 0.17), GA12 (0.64 +/- 0.21), GA19 (0.18
      +/- 0.09), GA20 (0.78 +/- 0.15), GA24 (0.38 +/- 0.09), GA34 (0.35 +/- 0.10), and
      GA53 (0.17 +/- 0.05). Plant growth promotion in cucumber, tomato, and young
      radish plants further evidenced the potential of this strain as a PGP bacterium.
      The results suggest that GA secretion by L. soli SE134 might prove advantageous
      for its ameliorative role in crop growth. These findings can be extended for
      improving the productivity of different crops under diverse environmental
      conditions.

PMID- 24100625
TI  - Purification and characterization of alpha-neoagarooligosaccharide hydrolase from
      Cellvibrio sp. OA-2007.
AB  - alpha-Neoagarooligosaccharide (alpha-NAOS) hydrolase was purified from Cellvibrio
      sp. OA-2007 by using chromatographic techniques after hydroxyapatite adsorption.
      The molecular masses of alpha-NAOS hydrolase estimated using SDS-PAGE and gel
      filtration chromatography were 40 and 93 kDa, respectively, and the optimal
      temperature and pH for the enzyme activity were 32oC and 7.0-7.2. alpha-NAOS
      hydrolase lost 43% of its original activity when incubated at 35oC for 30 min.
      The enzyme hydrolyzed neoagarobiose, neoagarotetraose, and neoagarohexaose to
      galactose, agarotriose, and agaropentaose, respectively, and produced 3,6-anhydro
      L-galactose concomitantly; however, it did not degrade agarose.

PMID- 24100626
TI  - The cancer diaspora: Metastasis beyond the seed and soil hypothesis.
AB  - Do cancer cells escape the confinement of their original habitat in the primary
      tumor or are they forced out by ecologic changes in their home niche? Describing
      metastasis in terms of a simple one-way migration of cells from the primary to
      the target organs is an insufficient concept to cover the nuances of cancer
      spread. A diaspora is the scattering of people away from an established homeland.
      To date, "diaspora" has been a uniquely human term used by social scientists;
      however, the application of the diaspora concept to metastasis may yield new
      biologic insights as well as therapeutic paradigms. The diaspora paradigm takes
      into account, and models, several variables including: the quality of the primary
      tumor microenvironment, the fitness of individual cancer cell migrants as well as
      migrant populations, the rate of bidirectional migration of cancer and host cells
      between cancer sites, and the quality of the target microenvironments to
      establish metastatic sites. Ecologic scientific principles can be applied to the
      cancer diaspora to develop new therapeutic strategies. For example, ecologic
      traps - habitats that lead to the extinction of a species - can be developed to
      attract cancer cells to a place where they can be better exposed to treatments or
      to cells of the immune system for improved antigen presentation. Merging the
      social science concept of diaspora with ecologic and population sciences concepts
      can inform the cancer field to understand the biology of tumorigenesis and
      metastasis and inspire new ideas for therapy.

PMID- 24100627
TI  - Adrenomedullin blockade suppresses growth of human hormone-independent prostate
      tumor xenograft in mice.
AB  - PURPOSE: To study the role of the adrenomedullin system [adrenomedullin and its
      receptors (AMR), CLR, RAMP2, and RAMP3] in prostate cancer androgen-independent
      growth. EXPERIMENTAL DESIGN: Androgen-dependent and -independent prostate cancer
      models were used to investigate the role and mechanisms of adrenomedullin in
      prostate cancer hormone-independent growth and tumor-associated angiogenesis and
      lymphangiogenesis. RESULTS: Adrenomedullin and AMR were immunohistochemically
      localized in the carcinomatous epithelial compartment of prostate cancer
      specimens of high grade (Gleason score >7), suggesting a role of the
      adrenomedullin system in prostate cancer growth. We used the androgen-independent
      Du145 cells, for which we demonstrate that adrenomedullin stimulated cell
      proliferation in vitro through the cAMP/CRAF/MEK/ERK pathway. The proliferation
      of Du145 and PC3 cells is decreased by anti-adrenomedullin antibody (alphaAM),
      supporting the fact that adrenomedullin may function as a potent
      autocrine/paracrine growth factor for prostate cancer androgen-independent cells.
      In vivo, alphaAM therapy inhibits the growth of Du145 androgen-independent
      xenografts and interestingly of LNCaP androgen-dependent xenografts only in
      castrated animals, suggesting strongly that adrenomedullin might play an
      important role in tumor regrowth following androgen ablation. Histologic
      examination of alphaAM-treated tumors showed evidence of disruption of tumor
      vascularity, with depletion of vascular as well as lymphatic endothelial cells
      and pericytes, and increased lymphatic endothelial cell apoptosis. Importantly,
      alphaAM potently blocks tumor-associated lymphangiogenesis, but does not affect
      established vasculature and lymphatic vessels in normal adult mice. CONCLUSIONS:
      We conclude that expression of adrenomedullin upon androgen ablation in prostate
      cancer plays an important role in hormone-independent tumor growth and in
      neovascularization by supplying/amplifying signals essential for pathologic
      neoangiogenesis and lymphangiogenesis. Clin Cancer Res; 19(22); 6138-50. (c)2013
      AACR.

PMID- 24100628
TI  - Targeting SRC and tubulin in mucinous ovarian carcinoma.
AB  - PURPOSE: To investigate the antitumor effects of targeting Src and tubulin in
      mucinous ovarian carcinoma. EXPERIMENTAL DESIGN: The in vitro and in vivo effects
      and molecular mechanisms of KX-01, which inhibits Src pathway and tubulin
      polymerization, were examined in mucinous ovarian cancer models. RESULTS: In
      vitro studies using RMUG-S and RMUG-L cell lines showed that KX-01 inhibited cell
      proliferation, induced apoptosis, arrested the cell cycle at the G2-M phase, and
      enhanced the cytotoxicity of oxaliplatin in the KX-01-sensitive cell line, RMUG
      S. In vivo studies showed that KX-01 significantly decreased tumor burden in RMUG
      S and RMUG-L mouse models relative to untreated controls, and the effects were
      greater when KX-01 was combined with oxaliplatin. KX-01 alone and in combination
      with oxaliplatin significantly inhibited tumor growth by reducing cell
      proliferation and inducing apoptosis in vivo. PTEN knock-in experiments in RMUG-L
      cells showed improved response to KX-01. Reverse phase protein array analysis
      showed that in addition to blocking downstream molecules of Src family kinases,
      KX-01 also activated acute stress-inducing molecules. CONCLUSION: Our results
      showed that targeting both the Src pathway and tubulin with KX-01 significantly
      inhibited tumor growth in preclinical mucinous ovarian cancer models, suggesting
      that this may be a promising therapeutic approach for patients with mucinous
      ovarian carcinoma.

PMID- 24100630
TI  - Aberrant expression of the PRAC gene in prostate cancer.
AB  - Identification of aberrant expression patterns of genes in prostate cancer (PCa)
      is a key step towards the development of effective therapies. Prostate-specific
      antigen (PSA) levels are commonly measured for the early detection of PCa, but
      which itself is still not an ideal biomarker. We analysed the expression patterns
      of prostate cancer susceptibility candidate (PRAC) in prostate cancer. The PRAC
      gene is known to be commonly expressed in prostate tissue, rectum and colon. To
      provide clear insights into the expression patterns of PRAC in PCa, we examined
      the gene expression by quantitative real-time PCR (qRT-PCR), western blot
      analysis and immunohistochemistry (IHC). The results showed that PRAC expression
      levels in androgen-insensitive cells (DU145 and PC3) are lower than those in
      androgen-sensitive cell lines (LNCaP, LNCaP-R and CW22R). However, treatment of
      the LNCaP cell line with androgen and anti-androgen demonstrated that PRAC is
      expressed in an androgen-independent manner. Further, PRAC expression was
      restored upon treatment of DU145 and PC3 cells with the methyltransferase
      inhibitor, 5-aza-2'-deoxycytidine (5-aza-CdR), which indicates the effect of
      methylation in the control of PRAC expression. In addition, IHC analysis revealed
      a significantly decreased immunoreactivity of PRAC protein in PCa tissues
      compared to benign prostatic hyperplasia (BPH) (p<0.0001). Thus, our findings
      suggest that the pathogenesis of PCa may be due to the expression levels of PRAC
      protein, and this protein can serve as a potential biomarker for the management
      of PCa. 

PMID- 24100629
TI  - Cellular therapy to target neuroinflammation in amyotrophic lateral sclerosis.
AB  - Neurodegenerative disorders are characterized by the selective vulnerability and
      progressive loss of discrete neuronal populations. Non-neuronal cells appear to
      significantly contribute to neuronal loss in diseases such as amyotrophic lateral
      sclerosis (ALS), Parkinson, and Alzheimer's disease. In ALS, there is
      deterioration of motor neurons in the cortex, brainstem, and spinal cord, which
      control voluntary muscle groups. This results in muscle wasting, paralysis, and
      death. Neuroinflammation, characterized by the appearance of reactive astrocytes
      and microglia as well as macrophage and T-lymphocyte infiltration, appears to be
      highly involved in the disease pathogenesis, highlighting the involvement of non
      neuronal cells in neurodegeneration. There appears to be cross-talk between motor
      neurons, astrocytes, and immune cells, including microglia and T-lymphocytes,
      which are subsequently activated. Currently, effective therapies for ALS are
      lacking; however, the non-cell autonomous nature of ALS may indicate potential
      therapeutic targets. Here, we review the mechanisms of action of astrocytes,
      microglia, and T-lymphocytes in the nervous system in health and during the
      pathogenesis of ALS. We also evaluate the therapeutic potential of these cellular
      populations, after transplantation into ALS patients and animal models of the
      disease, in modulating the environment surrounding motor neurons from pro
      inflammatory to neuroprotective. We also thoroughly discuss the recent advances
      made in the field and caveats that need to be overcome for clinical translation
      of cell therapies aimed at modulating non-cell autonomous events to preserve
      remaining motor neurons in patients. 

PMID- 24100631
TI  - Drosophila Kdm4 demethylases in histone H3 lysine 9 demethylation and ecdysteroid
      signaling.
AB  - The dynamic regulation of chromatin structure by histone post-translational
      modification is an essential regulatory mechanism that controls global gene
      transcription. The Kdm4 family of H3K9me2,3 and H3K36me2,3 dual specific histone
      demethylases has been implicated in development and tumorigenesis. Here we show
      that Drosophila Kdm4A and Kdm4B are together essential for mediating ecdysteroid
      hormone signaling during larval development. Loss of Kdm4 genes leads to globally
      elevated levels of the heterochromatin marker H3K9me2,3 and impedes
      transcriptional activation of ecdysone response genes, resulting in developmental
      arrest. We further show that Kdm4A interacts with the Ecdysone Receptor (EcR) and
      colocalizes with EcR at its target gene promoter. Our studies suggest that Kdm4A
      may function as a transcriptional co-activator by removing the repressive histone
      mark H3K9me2,3 from cognate promoters. 

PMID- 24100632
TI  - A hemizygous GYG2 mutation and Leigh syndrome: a possible link?
AB  - Leigh syndrome (LS) is an early-onset progressive neurodegenerative disorder
      characterized by unique, bilateral neuropathological findings in brainstem, basal
      ganglia, cerebellum and spinal cord. LS is genetically heterogeneous, with the
      majority of the causative genes affecting mitochondrial malfunction, and many
      cases still remain unsolved. Here, we report male sibs affected with LS showing
      ketonemia, but no marked elevation of lactate and pyruvate. To identify their
      genetic cause, we performed whole exome sequencing. Candidate variants were
      narrowed down based on autosomal recessive and X-linked recessive models. Only
      one hemizygous missense mutation (c.665G>C, p.W222S) in glycogenin-2 (GYG2)
      (isoform a: NM_001079855) in both affected sibs and a heterozygous change in
      their mother were identified, being consistent with the X-linked recessive trait.
      GYG2 encodes glycogenin-2 (GYG2) protein, which plays an important role in the
      initiation of glycogen synthesis. Based on the structural modeling, the mutation
      can destabilize the structure and result in protein malfunctioning. Furthermore,
      in vitro experiments showed mutant GYG2 was unable to undergo the self
      glucosylation, which is observed in wild-type GYG2. This is the first report of
      GYG2 mutation in human, implying a possible link between GYG2 abnormality and LS.

PMID- 24100634
TI  - ETV1 induces epithelial to mesenchymal transition in human gastric cancer cells
      through the upregulation of Snail expression.
AB  - The ETS family of transcription factors is involved in several physiological and
      pathological processes including tumor progression. The ETS transcription factors
      are divided into subfamilies based on the sequence and location of the ETS
      domain. ETV1 (Ets variant gene 1; also known as ER81), is a member of the PEA3
      subfamily, which has been found to promote metastatic progression in several
      types of human cancer. Previous findings demonstrated that ETV1 expression is
      upregulated in gastric adenocarcinomas; however, the underlying mechanisms of
      ETV1-induced metastatic progression in gastric cancer remain elusive. In the
      present study, we found that the overexpression of ETV1 in normal gastric
      epithelial cells resulted in epithelial to mesenchymal transition (EMT) and
      increased invasiveness. Conversely, knockdown of ETV1 resulted in decreased
      aggressiveness of the invasive gastric cancer cells. Mechanistically, ETV1
      transcriptionally upregulates Snail expression. Of note, ETV1 expression is
      significantly correlated with Snail expression in human gastric tumor samples. In
      summary, we present data that ETV1 promotes Snail expression to induce EMT-like
      metastatic progression in gastric cancer. 

PMID- 24100633
TI  - No evidence of interaction between known lipid-associated genetic variants and
      smoking in the multi-ethnic PAGE population.
AB  - Genome-wide association studies (GWAS) have identified many variants that
      influence high-density lipoprotein cholesterol, low-density lipoprotein
      cholesterol, and/or triglycerides. However, environmental modifiers, such as
      smoking, of these known genotype-phenotype associations are just recently
      emerging in the literature. We have tested for interactions between smoking and
      49 GWAS-identified variants in over 41,000 racially/ethnically diverse samples
      with lipid levels from the Population Architecture Using Genomics and
      Epidemiology (PAGE) study. Despite their biological plausibility, we were unable
      to detect significant SNP * smoking interactions.

PMID- 24100635
TI  - Follow-up study to assess the use and performance of household filters in Zambia.
AB  - Effective household water treatment can improve drinking water quality and
      prevent disease if used correctly and consistently over time. One year after
      completion of a randomized controlled study of water filters among households in
      Zambia with children < 2 years old and mothers who were human immunodeficiency
      virus (HIV)-positive, we conducted a follow-up study to assess use and
      performance of new filters distributed at the conclusion of the study; 90% of
      participating households met the criteria for current users, and 75% of
      participating households had stored water with lower levels of fecal
      contamination than source water. Microbiologically, the filters continued to
      perform well, removing an average of 99.0% of fecal indicator bacteria. Although
      this study provides some encouraging evidence about the potential to maintain
      high uptake and filter performance, even in the absence of regular household
      visits, additional research is necessary to assess whether these results can be
      achieved over longer periods and with larger populations.

PMID- 24100636
TI  - Comparison of the Easyshade Compact and Advance in vitro and in vivo.
AB  - OBJECTIVE: The objective of this study was to evaluate the repeatability, inter
      examiner and inter-device reliability, and accuracy of the new VITA Easyshade
      Advance (ES-A) spectrophotometer in comparison with the Easyshade Compact (ES-C).
      METHODS: For the in vitro study, six porcelain disks of random shade mixtures
      were fabricated from VITA ceramic powders. To analyze the repeatability of the ES
      C and ES-A, readings were obtained by one examiner for one porcelain disk and one
      shade tab (VITA 3D-Master). Measurements were repeated by two examiners to
      evaluate inter-examiner reliability. To assess accuracy, porcelain disks and
      shade tabs were measured with the ES-C and ES-A and by means of a
      spectroradiometer (SR). ?E values between the shade tabs and disks were
      calculated. Differences between devices were evaluated by use of univariate
      analysis. Reliability and accuracy of both devices were also tested in a clinical
      setting. The intra-class correlation coefficient (ICC) was calculated for all
      assessments of reliability. RESULTS: Good agreement was observed for replicate
      measurements (ICC > 0.9), for inter-examiner reliability of the ES-A and ES-C
      (ICC > 0.9), and for inter-device agreement (ICC > 0.9). Univariate analysis
      revealed that ?E values for the spectrophotometers were consistent (p = 0.783);
      spectroradiometrically measured ?E was comparable, but the mean value was smaller
      than that for the spectrophotometers (p = 0.004). Clinical inter-device agreement
      was acceptable to high (ICC > 0.777). The accuracy of the ES-A was higher than
      that of the ES-C (p = 0.001). CONCLUSION: Within the limitations of the
      experiment, the spectrophotometers tested enabled reliable and accurate
      measurement. In the clinical setting, however, the ES-A seems more accurate.
      CLINICAL RELEVANCE: ES-C and ES-A can be valuable tools for the determination of
      tooth colors. Because of their good reliability, they should especially be used
      for the assessment of tooth color changes over time.

PMID- 24100637
TI  - Effects of high-fluoride dentifrice (5,000-ppm) on caries-related plaque and
      salivary variables.
AB  - OBJECTIVES: The aim of the present study was to measure the effects of a 5,000
      ppm F toothpaste on caries-related factors in dental plaque and saliva. MATERIALS
      AND METHODS: A 6-week clinical trial was designed with a total of 34
      participants, of which 26 completed the study. The participants were assessed on
      four visits, 2 weeks apart. Sampling of approximal fluid for fluoride analysis
      and approximal plaque for organic acid analysis was performed. Chair-side tests
      were performed to register the lactic acid production rate on the tongue using
      ClinproTM Cario L-PopTM, approximal plaque pH using the pH "strip method" and
      salivary buffer capacity and counts of cariogenic microorganisms using CRT
      Buffer((r)) and CRT Bacteria((r)). RESULTS: Six weeks' use of 5,000-ppm
      fluoridated (F) toothpaste significantly increased the approximal fluid F
      concentration (p < 0.05). There was a significant decrease in lactic acid
      production rate on the tongue assessed by ClinproTM (p < 0.05). This was
      accompanied by changes in interproximal plaque acidogenicity, including
      significant reductions in AUC(5.7), AUC(6.2) and maximum pH fall and an increase
      in minimum pH (p < 0.05). A significant increase in the salivary buffer capacity
      and a reduction in the salivary mutans streptococci were observed (p < 0.05).
      CONCLUSION: The present study demonstrates the ability of 5,000-ppm F toothpaste
      to modify caries-related factors in dental plaque and saliva. CLINICAL RELEVANCE:
      The 5,000-ppm F toothpaste could be regarded as a possible effective regimen
      against caries in the near future.

PMID- 24100638
TI  - Porosity and root dentine to material interface assessment of calcium silicate
      based root-end filling materials.
AB  - OBJECTIVES: The aim of this study was to evaluate the porosity and assess the
      root dentine to material interface of four root-end filling materials based on
      tricalcium silicate cement using two microscopy techniques. METHODS: The porosity
      of Bioaggregate, Biodentine, a prototype radiopacified tricalcium silicate cement
      (TCS-20-Zr) and intermediate restorative material (IRM) was evaluated after
      immersion for 28 days in Hank's balanced salt solution (HBSS) using mercury
      intrusion porosimetry. The root dentine to material interface of the cements when
      used as root-end filling materials in extracted human teeth was assessed after 28
      days of dry storage and immersion in HBSS using a confocal microscope together
      with fluorescent tracers and also a field emission gun scanning electron
      microscope. RESULTS: Biodentine and IRM exhibited the lowest level or degree of
      porosity. The confocal microscopy used in conjunction to fluorescent tracers
      demonstrated that dry storage resulted in gaps at the root dentine to material
      interface and also cracks in the material with Biodentine being the most
      affected. Zinc was shown to be present in root dentine adjacent to the IRM
      restorations. CONCLUSIONS: Dry storage of Biodentine resulted in changes in the
      material microstructure and cracks at the root dentine to Biodentine interface.
      Furthermore, the gaps resulting from material shrinkage allowed the passage of
      the fluorescent microspheres thus indicating that these gaps are significant and
      can potentially allow the passage of micro-organisms.

PMID- 24100639
TI  - A novel approach to evaluate the effect of medicaments used in endodontic
      regeneration on root canal surface indentation.
AB  - OBJECTIVES: The aim of this study was to investigate the capability of a novel
      reference point indentation apparatus to test the indentation properties of root
      canal surface dentine treated with three intracanal medicaments used in
      endodontic regeneration. MATERIALS AND METHODS: Immature human premolars were
      selected (n = 22). Four specimens were obtained from each root and randomly
      assigned to three treatment groups and a control group. Each specimen was exposed
      to one of the three treatment pastes (triple antibiotic (TAP), double antibiotic
      (DAP), or calcium hydroxide (Ca(OH)2)) or neutral deionized water (control) for 1
      or 4 weeks. After each time interval, the indentation properties of the root
      canal dentine surfaces were measured using a BioDent reference point indenter.
      Two-way ANOVA and Fisher's protected least significant differences were used for
      statistical analyses. RESULTS: Significant differences in indentation parameters
      and estimated hardness between all groups at both time points were found. TAP
      treated dentine had the highest significant indentation parameters, followed by
      DAP-treated dentine, untreated control dentine, and Ca(OH)2-treated dentine,
      respectively. Furthermore, TAP-treated dentine had the lowest significant
      estimated hardness, followed by DAP-treated dentine, untreated control dentine,
      and Ca(OH)2-treated dentine, respectively. CONCLUSION: BioDent reference point
      indenter was able to detect significant differences in indentation properties of
      root canal dentine treated with various medicaments. CLINICAL RELEVANCE: The use
      of a reference point indenter is a promising approach to characterize the
      indentation properties of root canal surfaces without any surface modification.
      This might provide an in vitro mechanical measurement that is more representative
      of the actual clinical situation.

PMID- 24100641
TI  - Papillary calcifications: a new prognostic factor in idiopathic calcium oxalate
      urolithiasis.
AB  - Metabolic evaluation is not suitable to forecast the course of the disease in
      idiopathic calcium oxalate stone formation (iCaOxU). An important pathway in CaOx
      stone formation is the overgrowth on interstitial apatite papillary plaques.
      Therefore, we studied whether the extent of such plaques may be used as a
      prognostic factor in CaOxU. Prospectively, we studied n = 100 patients with
      iCaOxU. For stone analysis, X-ray diffraction/polarizing microscopy was used.
      During flexible ureteroscopy and flexible percutaneous nephrolithotomy, all the
      renal papillae were inspected, counted and the severity of calcifications
      assessed. A calcification index (CI) was calculated: sum of the No. of papillae *
      calcification grade (1-3) * No. of calcified/total No. of papillae. Furthermore,
      the following parameters were examined in all patients: age, sex, BMI, arterial
      blood pressure, stone episodes, DM; blood: creatinine, glucose, uric acid,
      calcium, sodium and potassium; urine: pH, volume, calcium, uric acid, citrate,
      ammonia and urea. Using the statistic programme Prism 5 (GraphPad), summary
      statistics and non-parametric correlations (Spearman) and their significance were
      calculated. The CI correlated significantly (r = 0.37; p = 0.012) with the No. of
      stone episodes. Apart from citrate (r = 0.51; p = 0.002), none of the
      conventional metabolic parameters correlated significantly with the No. of stone
      episodes. Paradoxically, the citrate excretion-although citrate being an
      inhibitor of CaOx stone formation-positively correlated to the recurrence rate.
      The endoscopic assessment of papillary plaques/calcifications and the calculation
      of the CI are a more suitable prognostic factor in CaOx than conventional
      metabolic evaluation. 

PMID- 24100640
TI  - Long-distance axonal transport of AAV9 is driven by dynein and kinesin-2 and is
      trafficked in a highly motile Rab7-positive compartment.
AB  - Adeno-associated virus (AAV) vectors can move along axonal pathways after brain
      injection, resulting in transduction of distal brain regions. This can enhance
      the spread of therapeutic gene transfer and improve treatment of neurogenetic
      disorders that require global correction. To better understand the underlying
      cellular mechanisms that drive AAV trafficking in neurons, we investigated the
      axonal transport of dye-conjugated AAV9, utilizing microfluidic primary neuron
      cultures that isolate cell bodies from axon termini and permit independent
      analysis of retrograde and anterograde axonal transport. After entry, AAV was
      trafficked into nonmotile early and recycling endosomes, exocytic vesicles, and a
      retrograde-directed late endosome/lysosome compartment. Rab7-positive late
      endosomes/lysosomes that contained AAV were highly motile, exhibiting faster
      retrograde velocities and less pausing than Rab7-positive endosomes without
      virus. Inhibitor experiments indicated that the retrograde transport of AAV
      within these endosomes is driven by cytoplasmic dynein and requires Rab7
      function, whereas anterograde transport of AAV is driven by kinesin-2 and
      exhibits unusually rapid velocities. Furthermore, increasing AAV9 uptake by
      neuraminidase treatment significantly enhanced virus transport in both
      directions. These findings provide novel insights into AAV trafficking within
      neurons, which should enhance progress toward the utilization of AAV for improved
      distribution of transgene delivery within the brain. 

PMID- 24100643
TI  - Emerging association between androgen deprivation therapy and male meningioma:
      significant expression of luteinizing hormone-releasing hormone receptor in male
      meningioma.
AB  - BACKGROUND: There is emerging data suggesting a potential risk for meningioma
      growth stimulation in patients on luteinizing hormone-releasing hormone (LHRH)
      analogs for prostate cancer. We examined the expression of LHRH receptor (LHRH
      R), progesterone receptor (PR) and Ki67 labeling index (LI) in specimens from
      male meningioma (MM) and female meningioma (FM) patients. METHODS: A total of 24
      MM and 24 FM paraffin blocks were retrieved from our institution between 1991 and
      2008. Sections from the paraffin blocks were stained with mouse monoclonal
      antibodies against LHRH-R, PR and Ki67. All male patients had no previous history
      of prostate cancer (PCa) or previous history of hormone therapy. RESULTS: LHRH-R
      positivity was extensive in 92% of MM and 88% of FM samples, with both showing
      strong intensity (67% and 79%, respectively). PR was positive in 20 of 24 (83%)
      MM and 23 of 24 (96%) FM samples. MM is less likely to exhibit Ki67 LI >4%
      compared with FM. CONCLUSIONS: The majority of MM and FM samples were strongly
      positive for LHRH-R expression and PR expression. The emerging association of
      androgen deprivation therapy and meningioma growth should be recognized in
      urological practice. Caution should be taken when considering LHRH agonist
      administration for patients with PCa and concurrent meningioma or previous
      history of meningioma.

PMID- 24100642
TI  - The effect of the frequency and duration of PSA measurement on PSA doubling time
      calculations in men with biochemically recurrent prostate cancer.
AB  - BACKGROUND: PSA doubling time (PSADT) is an attractive intermediate end point for
      assessing novel therapies in biochemically recurrent prostate cancer (BRPC). This
      study explores whether PSADT calculations are influenced by frequency/duration of
      PSA measurements, and whether statistical variability leads investigators to find
      false significant results. METHODS: In retrospective analyses of two BRPC
      cohorts: Johns Hopkins Hospital (JHH) patients who deferred therapy and placebo
      patients on a randomized clinical trial (RCT), we calculated changes in PSADT
      from early measurements to later measurements using subsets of available PSAs for
      patients with >=6 and >=9 PSAs. We simulated hypothetical single-arm trials using
      randomly selected, 50-patient subsets and simulated two-arm RCTs. RESULTS: JHH
      cohort (n=205) had median follow-up 58 months, median age 61 years and median
      Gleason 7. PSA variability changed with duration of PSA measurement as median
      within-patient PSADT increases for men with >6 PSAs ranged from 1.0 to 1.4 months
      by PSA subset while increases for men with >=9 PSAs ranged from 3.9 to 4.1
      months. Frequency of measurement did not change PSA variability as PSADT increase
      was unchanged when odd values were used instead of all values. Approximately 30%
      of JHH men experienced >200% increases in PSADT. Up to 62% of 50-patient single
      arm simulations detected a significant PSADT change, whereas simulated RCTs did
      not. Results were supported in the RCT placebo cohort; 46% of patients
      experienced PSADT increases >200%. CONCLUSIONS: These data suggest that
      calculated PSADT in BRPC may naturally increase over time in the absence of
      therapy and may be influenced by duration of PSA follow-up. As a result, single
      arm trials could show false significant increases despite the lack of active
      treatment of these patients. Placebo-controlled RCTs including clinical end
      points are recommended to screen novel agents in men with BRPC to mitigate bias
      because of natural PSADT variability.

PMID- 24100645
TI  - Association of paraoxonase gene polymorphisms with diabetic nephropathy and
      retinopathy.
AB  - Emerging reports have revealed a potential association of paraoxonase (PON) gene
      polymorphisms with diabetic nephropathy (DN) and diabetic retinopathy (DR).
      However, the identification of susceptible genes and the quantification of
      associated risks are elusive owing to a lack of reproducibility. Therefore, a
      meta-analysis was conducted in the present study to improve the understanding of
      the effect of PON1 and PON2 on DN and DR. A total of 10 articles, involving 2,877
      patients and 3,246 controls met the inclusion criteria. Functional variants (n=4)
      were evaluated, including rs662 (p.Q192R) and rs854560 (p.L55M) in PON1; and
      rs7493 (p.S311C) and rs12026 (p.A148G) in PON2. Overall, PON1-L55M was found to
      be significantly associated with DR in all the genetic models: allele [odds ratio
      (OR)=2.42; 95% confidence interval (CI), 1.91-3.07]; dominant (OR=5.76; 95% CI,
      3.14-10.55), homozygote (OR=10.53; 95% CI, 5.59-19.86), heterozygote (OR=3.62;
      95% CI, 1.94-6.74), and recessive (OR=3.56; 95% CI, 2.61-4.86), with no evidence
      of between-study heterogeneity. However, such associations were not detected in
      DN and the other three polymorphisms did not show any associations with DN or DR.
      The current meta-analysis highlighted results for the risk of association of PON1
      55L with DR. The results also indicated that PON2 gene polymorphisms, as well as
      PON1-Q192R, may not confer major genetic risk to DN or DR. Additional studies are
      required to enrich the understanding of PON genes, particularly for its
      functional role in DR.

PMID- 24100644
TI  - Metformin does not affect risk of biochemical recurrence following radical
      prostatectomy: results from the SEARCH database.
AB  - BACKGROUND: While epidemiologic studies suggest that metformin use among
      diabetics may decrease prostate cancer (PC) incidence, the effect of metformin
      use on PC outcome is unclear. We investigated the association between pre
      operative metformin use, dose and duration of use and biochemical recurrence
      (BCR) in PC patients with diabetes who underwent radical prostatectomy (RP).
      METHODS: We conducted a retrospective cohort analysis within the Shared Equal
      Access Regional Cancer Hospital (SEARCH) database of 371 PC patients with
      diabetes who underwent RP. Time to BCR between metformin users and non-users, and
      by metformin dose and duration of use was assessed using multivariable Cox
      proportional analysis adjusted for demographic, clinical and/or pathologic
      features. Time to castrate-resistant PC (CRPC), metastases and PC-specific
      mortality were explored as secondary outcomes using unadjusted analyses. RESULTS:
      Of 371 diabetic men, 156 (42%) were using metformin before RP. Metformin use was
      associated with more recent year of surgery (P<0.0001) but no clinical or
      pathologic characteristics. After adjustment for year of surgery, clinical and
      pathologic features, there were no associations between metformin use (hazard
      ratio (HR) 0.93; 95% confidence interval (CI) 0.61-1.41), high metformin dose (HR
      0.96; 95% CI 0.57-1.61) or duration of use (HR 1.00; 95% CI 0.99-1.02) and time
      to BCR. A total of 14 patients (3.8%) developed CRPC, 10 (2.7%) distant
      metastases and 8 (2.2%) died from PC. Unadjusted analysis suggested that high
      metformin dose vs non-use was associated with increased risk of CRPC (HR 5.1; 95%
      CI 1.6-16.5), metastases (HR 4.8; 95% CI 1.2-18.5) and PC-specific mortality (HR
      5.0; 95% CI 1.1-22.5). CONCLUSIONS: Metformin use, dose or duration of use was
      not associated with BCR in this cohort of diabetic PC patients treated with RP.
      The suggestion that higher metformin dose was associated with increased risk of
      CRPC, metastases and PC-specific mortality merits testing in large prospective
      studies with longer follow-up.

PMID- 24100647
TI  - Ischemic mitral regurgitation: current trends and treatment.
AB  - PURPOSE OF REVIEW: Ischemic mitral regurgitation (MR) is a common finding in
      patients with coronary artery disease. In this review, we summarize the current
      literature describing the treatment of ischemic mitral regurgitation. RECENT
      FINDINGS: Recent publications have focused on describing outcomes following the
      treatment of ischemic mitral regurgitation based on the specific mechanism of
      regurgitation. New therapies such as remodeling rings and percutaneous
      approaches, along with insights into mitral valve replacement, have advanced the
      treatment of ischemic mitral regurgitation. SUMMARY: Mitral valve surgery and
      concomitant coronary artery bypass grafting represent the most effective strategy
      for the treatment of severe symptomatic ischemic mitral regurgitation. Overall,
      the survival of patients with ischemic mitral regurgitation is poor. Advances in
      mitral valve repair may improve long-term durability of surgery, whereas evolving
      percutaneous therapies may be a treatment option for patients with functional
      mitral regurgitation who are not surgical candidates.

PMID- 24100648
TI  - Carotid endarterectomy: where do we stand at present?
AB  - PURPOSE OF REVIEW: The introduction of endovascular techniques and improvements
      in the medical management of atherosclerotic carotid lesions have led to changes
      in the modern management of stroke. The purpose of this review is to summarize
      the latest developments in surgical carotid intervention and highlight the
      current controversies. RECENT FINDINGS: The predominant controversies that
      dominate the correct surgical management of carotid atherosclerotic disease are:
      Notwithstanding the results of the Carotid Revascularisation Endarterectomy
      versus Stenting Trial, does carotid artery stenting produce equivalent outcomes
      to surgical carotid endarterectomy? Should recent developments in best medical
      management of these lesions and changing socioeconomic factors restrict the
      indication for surgical intervention for asymptomatic lesions? What is the ideal
      time frame for carotid interventions in symptomatic patients? SUMMARY: There is
      insufficient current or historic evidence to resolve these controversies and
      further large randomized controlled trials are therefore required. The current
      knowledge limits are explored.

PMID- 24100649
TI  - Inferior vena cava filters: indications and management.
AB  - PURPOSE OF REVIEW: The purpose of this review was to examine recent studies
      concerning the use of inferior vena cava (IVC) filters. RECENT FINDINGS: In the
      past 18 months, the American College of Chest Physicians released the 9th edition
      of their guideline for the prevention and treatment of venous thromboembolism.
      There have also been a number of studies reviewing the use of IVC filters in
      select populations for the prophylactic prevention of pulmonary embolism. Trauma
      continues to be the leading indication for prophylactic filters in a number of
      series, but further studies have demonstrated some benefit of prophylactic
      filters in the bariatric and spine surgery populations. The IVC filter
      complication rate remains low; however, so does the retrieval rate for
      potentially removable filters. These retrieval rates are increased with use of
      dedicated patient tracking mechanisms. Finally, there have been a number of
      technology updates in the hardware itself, focusing on strut design. SUMMARY:
      Despite little change in the society guidelines, the use of vena cava filters
      (VCFs) continues to rise. Overall, the use of IVC filters, especially in
      prophylactic situations, will remain controversial until randomized, controlled
      trials are performed within each specific patient population.

PMID- 24100650
TI  - Aortic root rupture: implications of catheter-guided aortic valve replacement.
AB  - PURPOSE OF REVIEW: The safety and efficiency of trans catheter aortic valve
      implantation (TAVI) has been clearly demonstrated. In high-risk patients, the
      number of procedures is constantly increasing and in western European countries
      this procedure is employed in more than 30% of isolated aortic valve
      replacements. The literature, however, focusing on perioperative aortic root
      (AoR) rupture is rather limited to just a few reports. The aim of this review is
      to analyze the pathophysiology of AoR rupture during TAVI, stressing the
      implications of the morphology of the AoR for this devastating complication.
      RECENT FINDINGS: Currently, perioperative AoR rupture ranges between 0.5 and 1.5%
      during TAVI, with almost 100% mortality. Recently, valve oversizing and balloon
      dilatation in a calcified and small AoR were considered as the most important
      predictive factors for this complication. SUMMARY: The most fragile unit of the
      AoR is its anchoring substrate to the ostium of the left ventricle. This
      membranous structure is not involved in the degenerative process leading to
      aortic valve stenosis. Due to the TAVI and/or balloon dilatation of the calcium
      stationed on the three leaflets and their attachment, a lesion may result on this
      structure. And, as a consequence, there is rupture of the AoR.

PMID- 24100651
TI  - Fractional flow reserve-guided coronary bypass surgery: should surgeons use it?
AB  - PURPOSE OF REVIEW: Physiology-based evaluation in stable ischemic heart disease
      is transforming percutaneous cardiovascular intervention (PCI). Fractional flow
      reserve (FFR)-guided PCI is associated with more appropriate and beneficial
      outcomes at lower costs. The surgical community can no longer ignore this
      development. We review evidence for the rationale, practicality and
      appropriateness of FFR-guided coronary artery bypass grafting (CABG), as compared
      with the current conventional, anatomy-based strategy for surgical
      revascularization. RECENT FINDINGS: Physiologic evaluation links the nature
      (anatomic or functional) of coronary stenoses to the perfused myocardium supplied
      by the target vessel and challenges the use of anatomy as the sole criterion for
      revascularization intervention. In CABG, a functional perfusion deficit/ischemia
      identifies myocardial territories that would physiologically benefit from
      revascularization by grafting beyond the functional stenosis. Conversely,
      deliberately not grafting beyond an anatomic stenosis would dramatically change
      the procedure of CABG. Recent studies of functionally guided revascularization
      (PCI or CABG) support this approach, while recent trials of PCI vs. CABG
      demonstrated a late survival advantage with anatomy-based CABG. Finally, new
      intraoperative imaging technologies are elucidating the physiologic consequences
      of surgical revascularization in real time, yielding insights into resolving this
      dilemma. SUMMARY: Physiologic-based revascularization is challenging our thinking
      about the historic strategy for CABG. Understanding better the physiologic
      consequences of revascularization will drive the evolution of CABG in the future.

PMID- 24100652
TI  - Endoscopic vessel harvesting: good or bad?
AB  - PURPOSE OF REVIEW: The use of less invasive approaches for saphenous vein or
      radial artery procurement in CABG surgery has gained popularity during the past
      decade. The purpose of the present review is to focus on the safety and the
      potential advantages of minimally invasive conduit harvesting in coronary
      surgery. RECENT FINDINGS: There is ample evidence in literature that the use of a
      less invasive approach for conduit (either saphenous vein or radial artery)
      procurement could yield consistent advantages over the conventional approach, in
      particular with respect to a lower incidence of wound complications, pain
      reduction and improved cosmetic results. Nevertheless, some recent studies raised
      concerns in terms of potential damage occurring to the harvested conduits with
      the endoscopic approach, which could therefore jeopardize the longevity of the
      graft itself. SUMMARY: Endoscopic conduit harvesting is a well-tolerated and
      effective procedure. The majority of scientific reports depicted that the
      minimally invasive approach does not compromise the quality of the harvested
      conduits and therefore does not lead to a higher incidence of graft failure or
      cardiac-related events in the mid-long term. The endoscopic technique should be
      the approach of choice for saphenous vein and radial artery procurement in CABG
      surgery; recent technical and technological advancements could further improve
      outcomes.

PMID- 24100653
TI  - US health insurance exchanges are swamped by users.

PMID- 24100654
TI  - Canadian drug safety initiative wins global support in campaign to have funding
      restored.

PMID- 24100655
TI  - Only a sixth of animal bite victims in India get antirabies treatment.

PMID- 24100656
TI  - Antimicrobial resistance will surge unless use of antibiotics in animal feed is
      reduced.

PMID- 24100658
TI  - The diagnostic yield of cardiac catheterization in low-risk troponinemia.

PMID- 24100657
TI  - Enhanced inducible costimulator ligand (ICOS-L) expression on dendritic cells in
      interleukin-10 deficiency and its impact on T-cell subsets in respiratory tract
      infection.
AB  - An association between inducible costimulator ligand (ICOS-L) expression and
      interleukin (IL)-10 production by dendritic cells (DCs) has been commonly found
      in infectious disease. DCs with higher ICOS-L expression and IL-10 production are
      reportedly more efficient in inducing regulatory T cells (Tregs). Here we use the
      Chlamydia muridarum (Cm) lung infection model in IL-10 knockout (KO) mice to test
      the relationship between IL-10 production and ICOS-L expression by DCs. We
      examined ICOS-L expression, the development of T-cell subsets, including Treg,
      Th17 and Th1 cell, in the background of IL-10 deficiency and its relationship
      with ICOS-L/ICOS signaling after infection. Surprisingly, we found that the IL-10
      KO mice exhibited significantly higher ICOS-L expression by DCs. Moreover, IL-10
      KO mice showed lower Tregs but higher Th17 and Th1 responses, but only the Th17
      response depended on ICOS signaling. Consistently, most of the Th17 cells were
      ICOS+, whereas most of the Th1 cells were ICOS- in the infected mice.
      Furthermore, neutralization of IL-17 in IL-10 KO mice significantly exacerbated
      lung infection. The data suggest that ICOS-L expression on DC may be negatively
      regulated by IL-10 and that ICOS-L expression on DC in the presence or absence of
      IL-10 costimulation may promote Treg or Th17 response, without significant impact
      on Th1.

PMID- 24100659
TI  - Design and additive manufacture for flow chemistry.
AB  - We review the use of additive manufacturing (AM) as a novel manufacturing
      technique for the production of milli-scale reactor systems. Five well-developed
      additive manufacturing techniques: stereolithography (SL), multi-jet modelling
      (MJM), selective laser melting (SLM), laser sintering (LS) and fused deposition
      modelling (FDM) were used to manufacture a number of miniaturised reactors which
      were tested using a range of organic and inorganic reactions. 

PMID- 24100661
TI  - Computer-Aided Vaccine Design.
AB  - Vaccines, and their discovery, are topics of singular importance in present-day
      biomedical science. The discovery of vaccines has hitherto been primarily
      empirical in nature, and it is only now that this is giving way, albeit very
      slowly, to a more rational approach, supported and enhanced by computer-based
      methods. In this context, the book "Computer-Aided Vaccine Design" by Tong and
      Ranganathan is a welcome new addition to the growing list of biomedical texts
      that address the computational discovery of vaccines and their components.

PMID- 24100660
TI  - Efficacy of the dual PI3K and mTOR inhibitor NVP-BEZ235 in combination with
      nilotinib against BCR-ABL-positive leukemia cells involves the ABL kinase domain
      mutation.
AB  - Imatinib, an ABL tyrosine kinase inhibitor (TKI), has shown clinical efficacy
      against chronic myeloid leukemia (CML). However, a substantial number of patients
      develop resistance to imatinib treatment due to the emergence of clones carrying
      mutations in the protein BCR-ABL. The phosphoinositide 3 kinase
      (PI3K)/Akt/mammalian target of rapamycin (mTOR) pathway regulates various
      processes, including cell proliferation, cell survival, and antiapoptosis
      activity. In this study, we investigated the efficacy of NVP-BEZ235, a dual PI3K
      and mTOR inhibitor, using BCR-ABL-positive cell lines. Treatment with NVP-BEZ235
      for 48 h inhibited cell growth and induced apoptosis. The phosphorylation of the
      AKT kinase, eukaryotic initiation factor 4-binding protein 1 (4E-BP1), and p70 S6
      kinase were decreased after NVP-BEZ235 treatment. The combination of NVP-BEZ235
      with a BCR-ABL kinase inhibitor, imatinib, or nilotinib, induced a more
      pronounced colony growth inhibition, whereas the combination of NVP-BEZ235 and
      nilotinib was more effective in inducing apoptosis and reducing the
      phosphorylation of AKT, 4E-BP1, and S6 kinase. NVP-BEZ235 in combination with
      nilotinib also inhibited tumor growth in a xenograft model and inhibited the
      growth of primary T315I mutant cells and ponatinib-resistant cells. Taken
      together, these results suggest that administration of the dual PI3K and mTOR
      inhibitor NVP-BEZ235 may be an effective strategy against BCR-ABL mutant cells
      and may enhance the cytotoxic effects of nilotinib in ABL TKI-resistant BCR-ABL
      mutant cells. 

PMID- 24100662
TI  - Both high reliability and giant electrocaloric strength in BaTiO3 ceramics.
AB  - BaTiO3 has a giant electrocaloric strength, |DeltaT|/|DeltaE|, because of a large
      latent heat and a sharp phase transition. The electrocaloric strength of a new
      single crystal, as giant as 0.48 K.cm/kV, is twice larger than the previous best
      result, but it remarkably decreased to 0.18 K.cm/kV after several times of
      thermal cycles accompanied by alternating electric fields, because the field
      induced phase transition and domain switching resulted in numerous defects such
      as microcracks. The ceramics prepared from nano-sized powders showed a high
      electrocaloric strength of 0.14 K.cm/kV, comparable to the single crystals
      experienced electrocaloric cycles, because of its unique microstructure after
      proper sintering process. Moreover, its properties did not change under the
      combined effects of thermal cycles and alternating electric fields, i.e. it has
      both large electrocaloric effect and good reliability, which are desirable for
      practical applications.

PMID- 24100663
TI  - [Cicatricial alopecias].
AB  - Cicatricial alopecias are a diagnostic and therapeutic challenge. The
      irreversibility and cosmetic sequelae of cicatricial alopecia demand special
      diagnostic attention. Loss of follicular orifices points to permanent hair loss,
      due to irreversible damage to essential parts of the follicle or destruction of
      the entire follicle. Where there is no obvious physical/chemical injury or acute
      infectious etiology, clinical differential diagnosis may be difficult. Clinical
      inspection is of limited usefulness. Accurate diagnosis based on a careful
      patient history, examination, microbiological studies, and scalp biopsy are
      prerequisite to therapy. On the basis of histology, a differentiation is made
      between primary cicatricial alopecias due to preferential destruction of the
      follicle, and secondary cicatricial alopecias resulting from events outside
      impinging upon and eradicating the follicle. The primary cicatricial alopecias
      include well-defined chronic inflammatory diseases differentiated depending on
      the type and pattern of inflammation. Although clinicopathologic features allow
      for diagnosis in most cases, therapeutic limits reflect the boundaries of our
      present understanding. With expanding technologies for dissecting the immunologic
      and molecular basis, there is hope for a deeper understanding of the underlying
      pathogenesis and novel therapeutic interventions. 

PMID- 24100664
TI  - Respiratory CO2 response in acute cervical spinal cord injury (CO2 response in
      spinal cord injury).
AB  - STUDY DESIGN: Retrospective study. OBJECTIVES: The objective of this study was to
      compare the CO2 response of acute tetraplegic cervical spinal cord injury (SCI)
      patients undergoing mechanical ventilation with a control group of critically ill
      patients ready for weaning of mechanical ventilation and successfully extubated.
      SETTING: This study was conducted at the intensive care unit of a University
      Hospital in Mallorca, Spain. METHODS: CO2 response was studied in 12 acute
      tetraplegic cervical SCI patients at the C4-C7 level and 22 control patients. The
      control group patients were consecutively selected from a database of patients
      with mechanical ventilation and who were successfully extubated after a CO2
      response test. To increase the CO2 , we used the method of re-inhalation of
      expired air, and we evaluated the hypercapnic ventilatory response, the change in
      minute ventilation induced by the increase of partial pressure of arterial carbon
      dioxide (PaCO2 ), which measures the whole respiratory system (metabolic control,
      neuromuscular or ventilatory apparatus), and the hypercapnic drive response, the
      change in the airway occlusion pressure at 100 ms induced by the increase in
      PaCO2, which measures the chemosensitivity of the respiratory center. RESULTS:
      Cervical SCI patients were younger than the control group patients (26+/-7 and
      62+/-12 years, respectively; P<0.001). Mean values of the hypercapnic ventilatory
      response in cervical SCI and control groups were 0.52+/-0.31 and 0.64+/-0.33 l
      min(-1) per mm Hg (P=0.40), respectively, and the hypercapnic drive response was
      0.24+/-0.16 and 0.48+/-0.23 cm H2O per mm Hg (P=0.001), respectively. CONCLUSION:
      Acute tetraplegic cervical SCI patients had reduced hypercapnic drive response
      that may contribute to the difficult weaning, without reduction in hypercapnic
      ventilatory response.

PMID- 24100665
TI  - Discrepancies in the estimates of life expectancy after SCI.

PMID- 24100666
TI  - Critical evaluation of assays for vitamin D status.
AB  - PURPOSE OF REVIEW: The objective is to highlight new aspects and methodological
      developments in the assessment of vitamin D status in clinical settings. RECENT
      FINDINGS: Recent advances in the assessment of vitamin D status mostly concern
      two areas: the emerging clinical and analytical interest in other circulating
      vitamin D metabolites [i.e. 3-epimer and 24,25-(OH)2 D] that opens a new
      perspective for the vitamin D metabolite profiling in health and disease and
      methodological improvements including the development of reference measurement
      procedures, the certification of Standard Reference Materials, the development
      and application of Standardization protocols and the change of the Vitamin D
      External Quality Assurance Survey (DEQAS) to an accuracy-based proficiency
      testing scheme. SUMMARY: Despite the improvement in the analytical imprecision
      between methods and laboratories over the last years, the reported prevalence of
      vitamin D deficiency in a given population still depends on the method used.
      Improvements in quality control procedures, however, will improve the
      standardization, accuracy and comparability of methods. At present, the
      analytical evaluation of other circulating vitamin D metabolites (vitamin D
      profiling) and their clinical utility is, however, limited to liquid
      chromatography users.

PMID- 24100667
TI  - Lipid droplet metabolism.
AB  - PURPOSE OF REVIEW: With the realization that lipid droplets are not merely inert
      fat storage organelles, but highly dynamic and actively involved in cellular
      lipid homeostasis, there has been an increased interest in lipid droplet biology.
      Recent studies have begun to unravel the roles that lipid dropletss play in
      cellular physiology and provide insights into the mechanisms by which lipid
      droplets contribute to cellular homeostasis. This review provides a summary of
      these recent publications on lipid droplet metabolism. RECENT FINDINGS:
      Perilipins have different preferences for associating with triacylglycerol (TAG)
      or cholesteryl esters, different tissue distributions, and each contributes to
      lipid metabolism in its unique way. Cell death-inducing DFF45-like effector
      proteins are not only involved in lipid droplet expansion, but also in the
      cellular response to stress and lipid secretion. Lipid droplets undergo an active
      cycle of lipolysis and re-esterification to form microlipid droplets. TAG
      synthesis for lipid droplet formation and expansion occurs in the endoplasmic
      reticulum and on lipid droplets, and TAG transfers between lipid droplets during
      lipid droplet fusion. Lipid droplets interact with the endoplasmic reticulum and
      mitochondria to facilitate lipid transfer, lipid droplet expansion, and
      metabolism. SUMMARY: Lipid droplets are dynamically active, responding to changes
      in cellular physiology, as well as interacting with cytosolic proteins and other
      organelles to control lipid homeostasis.

PMID- 24100669
TI  - Transient receptor potential activated brown fat thermogenesis as a target of
      food ingredients for obesity management.
AB  - PURPOSE OF REVIEW: Cold exposure activates brown adipose tissue (BAT), the major
      site of sympathetically activated nonshivering thermognenesis, via transient
      receptor potential (TRP) channels. Capsaicin and its nonpungent analogue
      (capsinoids) are agonists for a vanilloid subtype one of TRP, and have the
      potential to increase whole-body energy expenditure and reduce body fat. This
      article reviews the regulatory roles of BAT for energy expenditure and body fat
      in humans, particularly focusing on food ingredients activating the TRP-BAT axis.
      RECENT FINDINGS: Acute cold exposure increased energy expenditure in humans with
      metabolically active BAT, but not those without it. Quite similar responses were
      found after a single oral ingestion of either capsinoids or an alcohol extract of
      Guinea pepper seeds, indicating that these food ingredients activate BAT and
      thereby increase energy expenditure. When individuals without active BAT were
      exposed to cold every day for 6 weeks, BAT was recruited in association with
      increased energy expenditure and decreased body fat. A 6-week daily ingestion of
      capsinoids mimicked the effects of repeated cold exposure. These findings
      indicate that human BAT can be reactivated/recruited, thereby increasing energy
      expenditure and decreasing body fat. SUMMARY: Human BAT recruited by prolonged
      ingestion of a vanilloid subtype one of TRP agonists increases energy expenditure
      and decreases body fat. In addition to capsinoids, there are numerous food
      ingredients acting as TRP agonists, which are expected to activate BAT and so be
      useful for the prevention of obesity in daily life.

PMID- 24100668
TI  - Amino acid transporters in the regulation of human skeletal muscle protein
      metabolism.
AB  - PURPOSE OF REVIEW: To highlight recent research on amino acid sensing and
      signaling and the role of amino acid transporters in the regulation of human
      skeletal muscle protein metabolism. RECENT FINDINGS: The mechanisms that sense
      amino acid availability and activate mechanistic target of rapamycin complex 1
      signaling and protein synthesis are emerging, with multiple new proteins and
      intracellular amino acid sensors recently identified. Amino acid transporters
      have a role in the delivery of amino acids to these intracellular sensors and new
      findings provide further support for amino acid transporters as possible
      extracellular amino acid sensors. There is growing evidence in human skeletal
      muscle that amino acid transporter expression is dynamic and responsive to
      various stimuli, indicating amino acid transporters may have a unique role in the
      regulation of human skeletal muscle adaptation. SUMMARY: There is a clear need to
      further examine the role of amino acid transporters in human skeletal muscle and
      their link to cellular amino acid sensing and signaling in the control of protein
      metabolism. A better understanding of amino acid transport and transporters will
      allow us to optimize nutritional strategies to accelerate muscle health and
      improve outcomes for clinical populations.

PMID- 24100670
TI  - Iron and brain functions.
AB  - PURPOSE OF REVIEW: The purpose of this study is to highlight recent research
      findings that advance our understanding of the relation between iron status and
      neural functioning. RECENT FINDINGS: Recent findings have helped to answer
      questions pertaining to the interrelationship of iron and neural functioning in
      three primary areas: reversibility of changes occurring with early-life iron
      deficiency, association of severity of deficiency with negative outcomes and
      underlying mechanisms responsible for the cognitive and behavioural changes seen
      with iron deficiency. Results of recent studies indicate long-term negative
      consequences of early-life iron deficiency that may be irreversible and these
      negative consequences may be encountered by those with iron deficiency that has
      not yet reached the point of anaemia, indicating the likelihood that iron
      deficiency and not simply hypoxia from iron deficiency anaemia is causing the
      observed cognitive and behavioural alterations. Finally, recent studies have
      advanced our understanding of the underlying mechanisms by using animal models
      that isolate the deficiency to the hippocampus in addition to models that
      generate a whole-body iron deficiency. SUMMARY: These advances should help to
      inform policy, particularly with respect to preventing and treating iron
      deficiency and, thereby, improve the health status of millions of individuals
      worldwide.

PMID- 24100671
TI  - Nutritional potential of metabolic remodelling of white adipose tissue.
AB  - PURPOSE OF REVIEW: Recent findings in animals suggest that diet-related factors
      can programme adipose tissue features in early life and remodel white adipose
      tissue (WAT) towards a brown adipose tissue (BAT)-like phenotype in adulthood,
      while impacting on body fat content and susceptibility to obesity. The purpose of
      this review is to address the significance of these results and their
      applicability in humans. RECENT FINDINGS: Nutritional conditions in the perinatal
      period influence sympathetic innervation to WAT and WAT cellularity in rodents.
      Leptin intake during the suckling period prevents obesity and other metabolic
      alterations in later life in rats through mechanisms that include increased
      sensitivity of adipose tissues to leptin. Recent data support the thermogenic
      functionality of inducible brown-like cells in rodent WAT and functional
      thermogenic beige adipogenesis from human progenitor cells. Diet-related factors
      and exercise can promote BAT activation and/or WAT-to-BAT remodelling (WAT
      browning) in animals. SUMMARY: Animal studies suggest that adipose tissue health
      and whole body adiposity might be influenced by early life nutrition and
      lifestyle factors in adulthood impacting energy metabolism in adipose tissues.
      For this knowledge to be translated to humans, biomarkers allowing early
      detection of the programming status of the individual and technologies allowing
      measuring of the thermogenic activity of adipose tissue depots in vivo are
      required.

PMID- 24100672
TI  - Update on antioxidant micronutrients in the critically ill.
AB  - PURPOSE OF REVIEW: To evaluate recent evidence on pharmaconutrition with
      antioxidant micronutrients, for different populations of adult critically ill
      patients. RECENT FINDINGS: Over the last few years, different studies have shown
      that high-dose trace elements and vitamins, especially parenteral selenium and
      zinc, may be able to improve relevant clinical outcomes in the most seriously ill
      patients. High-dose selenite monotherapy reduces mortality, particularly when a
      pharmacological loading dose is given in the early stage of severe sepsis and
      septic shock. Notwithstanding, the recently published REducing Deaths due to
      OXidative Stress study using an antioxidant cocktail and parenteral selenite, in
      addition to standard enteral nutrition, was unable to show any benefits for
      patients with multiple organ failure. SUMMARY: There is evidence supporting the
      concept of pharmaconutrition with high-dose micronutrients. Selenium therapy may
      be able to decrease infections and reduce mortality in sepsis, but more research
      is needed to better understand pharmacokinetics, optimal composition, timing,
      duration, and dose of antioxidant cocktails for the critically ill.

PMID- 24100673
TI  - Protective effects of dark chocolate on endothelial function and diabetes.
AB  - PURPOSE OF REVIEW: Relationship between cocoa consumption and cardiovascular
      disease, particularly focusing on clinical implications resulting from the
      beneficial effects of cocoa consumption on endothelial function and insulin
      resistance. This could be of clinical relevance and may suggest the mechanistic
      explanation for the reduced risk of cardiovascular events reported in the
      different studies after cocoa intake. RECENT FINDINGS: Increasing evidence
      supports a protective effect of cocoa consumption against cardiovascular disease.
      Cocoa and flavonoids from cocoa have been described to improve endothelial
      function and insulin resistance. A proposed mechanism could be considered in the
      improvement of the endothelium-derived vasodilator nitric oxide by enhancing
      nitric oxide synthesis or by decreasing nitric oxide breakdown. SUMMARY: The
      endothelium plays a pivotal role in the arterial homeostasis, and insulin
      resistance is the most important pathophysiological feature in various
      prediabetic and diabetic states. Reduced nitric oxide bioavailability with
      endothelial dysfunction is considered the earliest step in the pathogenesis of
      atherosclerosis. Further, insulin resistance could account, at least in part, for
      the endothelial dysfunction. Endothelial dysfunction has been considered an
      important and independent predictor of future development of cardiovascular risk
      and events. Cocoa and flavonoids from cocoa might positively modulate these
      mechanisms with a putative role in cardiovascular protection.

PMID- 24100674
TI  - Health benefits of cocoa.
AB  - PURPOSE OF REVIEW: In modern society, cocoa is being eaten as a confectionery,
      contrary to its medicinal use in the past. However, since the last decade, there
      has been a revival of talks about cocoa's health beneficial effects. Development
      has been made at the molecular level recently. This review discusses the recent
      progresses on potential health benefits of cocoa and/or its derivatives, with a
      focus on the areas that have been paid little attention so far, such as the role
      of cocoa in immune regulation, inflammation, neuroprotection, oxidative stress,
      obesity, and diabetes control. RECENT FINDINGS: Thanks to the advancement in
      analytical technologies, the cocoa's metabolic pathways have now been properly
      mapped providing essential information on its roles. Cocoa helps in weight loss
      by improving mitochondrial biogenesis. It increases muscle glucose uptake by
      inserting glucose transporter 4 in skeletal muscles membrane. Because of its
      antioxidant properties, cocoa offers neuron protection and enhances cognition and
      positive mood. It lowers immunoglobulin E release in allergic responses. It can
      affect the immune response and bacterial growth at intestinal levels. It reduces
      inflammation by inhibiting nuclear factor-kappaB. SUMMARY: Keeping in view the
      pleiotropic health benefits of cocoa, it may have the potential to be used for
      the prevention/treatment of allergies, cancers, oxidative injuries, inflammatory
      conditions, anxiety, hyperglycemia, and insulin resistance.

PMID- 24100675
TI  - Gluco and galacto-oligosaccharides in food: update on health effects and
      relevance in healthy nutrition.
AB  - PURPOSE OF REVIEW: Much of the recent research literature in the field of
      prebiotics is on galacto-oligosaccharides. Gluco-oligosaccharides represent an
      interesting emerging class of candidate prebiotics. RECENT FINDINGS: Recent
      research on galacto-oligosaccharides has shown that these can have a positive
      impact on immunity, calcium absorption and markers of metabolic syndrome. The
      fact that galacto-oligosaccharides and gluco-oligosaccharides are enzymatically
      manufactured means that novel forms have been produced, and preliminary
      evaluation looks to be encouraging. SUMMARY: Galacto-oligosaccharides are rapidly
      gaining an impressive weight of evidence for health effects in humans. The field
      will generate novel molecules, which may be considered as prebiotics in the
      future.

PMID- 24100677
TI  - Translating nutritional potential of metabolic remodelling to disease-modifying
      nutritional management.

PMID- 24100676
TI  - Ghrelin: much more than a hunger hormone.
AB  - PURPOSE OF REVIEW: Ghrelin is a multifaceted gut hormone that activates its
      receptor, growth hormone secretagogue receptor (GHS-R). Ghrelin's hallmark
      functions are its stimulatory effects on growth hormone release, food intake and
      fat deposition. Ghrelin is famously known as the 'hunger hormone'. However, ample
      recent literature indicates that the functions of ghrelin go well beyond its role
      as an orexigenic signal. Here, we have reviewed some of the most recent findings
      on ghrelin and its signalling in animals and humans. RECENT FINDINGS: Ghrelin
      regulates glucose homeostasis by inhibiting insulin secretion and regulating
      gluconeogenesis/glycogenolysis. Ghrelin signalling decreases thermogenesis to
      regulate energy expenditure. Ghrelin improves the survival prognosis of
      myocardial infarction by reducing sympathetic nerve activity. Ghrelin prevents
      muscle atrophy by inducing muscle differentiation and fusion. Ghrelin regulates
      bone formation and metabolism by modulating proliferation and differentiation of
      osteoblasts. SUMMARY: In addition to ghrelin's effects on appetite and adiposity,
      ghrelin signalling also plays crucial roles in glucose and energy homeostasis,
      cardioprotection, muscle atrophy and bone metabolism. These multifaceted roles of
      ghrelin make ghrelin and GHS-R highly attractive targets for drug development.
      Ghrelin mimetics may be used to treat heart diseases, muscular
      dystrophy/sarcopenia and osteoporosis; GHS-R antagonists may be used to treat
      obesity and insulin resistance.

PMID- 24100678
TI  - JNK inhibitor SP600125 enhances TGF-beta-induced apoptosis of RBE human
      cholangiocarcinoma cells in a Smad-dependent manner.
AB  - Transforming growth factor beta (TGF-beta) signaling is pivotal for the
      progression of specific types of tumors at certain stages. However, the mechanism
      by which TGF-beta is regulated by other factors remains unclear. In this study,
      the involvement of SP600125, an inhibitor of c-Jun N-terminal kinase (JNK), in
      TGF-beta-induced apoptosis of the RBE human cholangiocarcinoma cell line was
      investigated. Exogenous TGF-beta1 activated Smad and non-Smad signaling pathways,
      including the JNK pathway in RBE cells, and induced apoptosis, which was
      inhibited by knockdown of Smad4 expression. SP600125 increased the TGF-beta1
      induced phosphorylation of Smad2 and Smad3, which enhanced the TGF-beta1-induced
      transcriptional response and apoptosis in RBE cells. The effect of SP600125 on
      the transcriptional response and apoptosis was reduced by knockdown of Smad4
      expression. In addition, TGF-beta1-induced apoptosis was abrogated using the pan
      caspase inhibitor Z-VAD-fmk. SP600125 promoted the TGF-beta1-induced caspase
      cleavage, while knockdown of Smad4 expression counteracted this effect. These
      results indicate that SP600125 enhances TGF-beta-induced apoptosis of RBE cells
      through a Smad-dependent pathway that involves Smad-dependent caspase activation.
      SP600125 is hypothesized to be an ideal therapeutic candidate for treating human
      cholangiocarcinoma.

PMID- 24100679
TI  - Preoperative treatment of locally advanced esophageal carcinoma (Review).
AB  - Esophageal cancer (EC) is an aggressive malignancy with increasing incidence
      worldwide. Surgery is still the most effective treatment, however, both the high
      rate of local and distant recurrences and surgery-related complications led us to
      investigate new preoperative strategies. In this review, we discuss the role of
      neoadjuvant therapy for locally advanced EC with a focus on preoperative
      chemoradiation (trimodality treatment). Furthermore, the last fifteen years of
      published literature and our experience have been also reviewed. In the
      preoperative setting, few trials have reported a significant benefit with
      fluoropyrimidine and platinum compound-based neoadjuvant chemotherapy, compared
      to surgery alone. A large number of phase III trials and meta-analyses have
      demonstrated improved outcomes with preoperative chemoradiation vs. neoadjuvant
      chemotherapy or surgery alone. Therefore, trimodality therapy can be considered
      the most effective option in the management of locally advanced EC. Addition of
      drugs targeting VEGF or HER2 to standard chemotherapy appears to be feasible but
      needs to be explored more accurately. FDG-PET may predict both response to
      neoadjuvant treatments and prognosis.

PMID- 24100680
TI  - The relevance of family variables in child and adolescent mental health.

PMID- 24100681
TI  - The effects of Bacillus thuringiensis Cry6A on the survival, growth,
      reproduction, locomotion, and behavioral response of Caenorhabditis elegans.
AB  - Several families of crystal proteins from Bacillus thuringiensis exhibit
      nematicidal activity. Cry5B protein, a pore-forming toxin, has been intensively
      studied yielding many insights into the mode of action of crystal protein at
      molecular level and pathogenesis of pore-forming toxins. However, little
      attention was paid to Cry6A, another representative nematicidal crystal protein.
      Cry6A shares very low homology with Cry5B at amino acid sequence and probably
      acts in a distinct pathway from Cry5B and even the other main commercial crystal
      proteins. In the current study, we comprehensively investigated the nematicidal
      properties of Cry6Aa2 against the free-living soil nematode Caenorhabditis
      elegans and examined the physical response of C. elegans to Cry6Aa2 attack. Our
      results indicate that Cry6Aa2 exhibits high lethal activity to C. elegans and
      could cause detrimental effects on C. elegans, including obviously suppressed
      growth, decreased brood size, and even abnormal motility. Meanwhile, our study
      additionally shows that C. elegans could defend against the Cry6Aa2 toxin harmful
      threat through behavioral defense responses, such as reduced oral uptake and
      physical avoidance. In general, this study suggests that Cry6Aa2 possesses
      diverse nematicidal properties, which strongly indicates that Cry6Aa2 is a
      promising potential candidate of nematicidal agent. Moreover, this study
      highlights the importance of behavioral responses in defense of C. elegans for
      survival and demonstrates the key role of crystal protein in the interaction of
      B. thuringiensis-C. elegans. These findings could shed light on understanding the
      interaction of C. elegans with B. thuringiensis and provide a perfect model to
      study the role of pathogenic factor in the interaction of pathogen-host. 

PMID- 24100682
TI  - Engineered short branched-chain acyl-CoA synthesis in E. coli and acylation of
      chloramphenicol to branched-chain derivatives.
AB  - Short branched-chain acyl-CoAs are important building blocks for a wide variety
      of pharmaceutically valuable natural products. Escherichia coli has been used as
      a heterologous host for the production of a variety of natural compounds for many
      years. In the current study, we engineered synthesis of isobutyryl-CoA and
      isovaleryl-CoA from glucose in E. coli by integration of the branched-chain alpha
      keto acid dehydrogenase complex from Streptomyces avermitilis. In the presence of
      the chloramphenicol acetyltransferase (cat) gene, chloramphenicol was converted
      to both chloramphenicol-3-isobutyrate and chloramphenicol-3-isovalerate by the
      recombinant E. coli strains, which suggested successful synthesis of isobutyryl
      CoA and isovaleryl-CoA. Furthermore, we improved the alpha-keto acid precursor
      supply by overexpressing the alsS gene from Bacillus subtilis and the ilvC and
      ilvD genes from E. coli and thus enhanced the synthesis of short branched-chain
      acyl-CoAs. By feeding 25 mg/L chloramphenicol, 2.96 +/- 0.06 mg/L chloramphenicol
      3-isobutyrate and 3.94 +/- 0.06 mg/L chloramphenicol-3-isovalerate were generated
      by the engineered E. coli strain, which indicated efficient biosynthesis of short
      branched-chain acyl-CoAs. HPLC analysis showed that the most efficient E. coli
      strain produced 80.77 +/- 3.83 nmol/g wet weight isovaleryl-CoA. To our
      knowledge, this is the first report of production of short branched-chain acyl
      CoAs in E. coli and opens a way to biosynthesize various valuable natural
      compounds based on these special building blocks from renewable carbon sources.

PMID- 24100683
TI  - Codon optimization, expression, purification, and functional characterization of
      recombinant human IL-25 in Pichia pastoris.
AB  - Interleukin (IL)-25 (also known as IL-17E) is a distinct member of the IL-17
      cytokine family which induces IL-4, IL-5, and IL-13 expression and promotes
      pathogenic T helper (Th)-2 cell responses in various organs. IL-25 has been shown
      to have crucial role between innate and adaptive immunity and also a key
      component of the protection of gastrointestinal helminthes. In this study, to
      produce bioactive recombinant human IL-25 (rhIL-25), the cDNA of mature IL-25 was
      performed codon optimization based on methylotropic yeast Pichia pastoris codon
      bias and cloned into the expression vector pPICZalphaA. The recombinant vector
      was transformed into P. pichia strain X-33 and selected by zeocin resistance.
      Benchtop fermentation and simple purification strategy were established to purify
      the rhIL-25 with about 17 kDa molecular mass. Functional analysis showed that
      purified rhIL-25 specifically bond to receptor IL-17BR and induce G-CSF
      production in vitro. Further annexin V-FITC/PI staining assay indicated that rhIL
      25 induced apoptosis in two breast cancer cells, MDA-MB-231 and HBL-100. This
      study provides a new strategy for the large-scale production of bioactive IL-25
      for biological and therapeutic applications. 

PMID- 24100684
TI  - Microbial deterioration of cultural heritage and works of art--tilting at
      windmills?
AB  - Microorganisms (bacteria, archaea and fungi), in addition to lichens and insect
      pests, cause problems in the conservation of cultural heritage because of their
      biodeteriorative potential. This holds true for all types of historic artefacts,
      and even for art made of modern materials, in public buildings, museums and
      private art collections. The variety of biodeterioration phenomena observed on
      materials of cultural heritage is determined by several factors, such as the
      chemical composition and nature of the material itself, the climate and exposure
      of the object, in addition to the manner and frequency of surface cleaning and
      housekeeping in museums. This study offers a review of a variety of well-known
      biodeterioration phenomena observed on different materials, such as stone and
      building materials, objects exhibited in museums and libraries, as well as human
      remains and burial-related materials. The decontamination of infected artefacts,
      exhibition rooms and depots incurs high expenditure for museums. Nevertheless,
      the question has to be raised: whether the process of biodeterioration of
      cultural heritage can or should be stopped under all circumstances, or whether we
      have to accept it as a natural and an implicit consecution of its creation. This
      study also highlights critically the pros and cons of biocide treatments and
      gives some prominent examples of successful and unsuccessful conservation
      treatments. Furthermore, an outlook on the future research needs and developments
      in this highly interesting field is given. 

PMID- 24100685
TI  - Regulation of ASIC1 by Ca2+/calmodulin-dependent protein kinase II in human
      glioblastoma multiforme.
AB  - Recent studies have implicated the acid-sensing ion channel 1 (ASIC1), a proton
      gated cation channel that belongs to the epithelial sodium channel
      (ENaC)/Degenerin family, plays an important role in glioma cell migration. Among
      the ASIC subunits, only ASIC1a has been found be calcium permeable. However, it
      has not been determined whether Ca2+/calmodulin-dependent protein kinase II
      (CaMKII) regulates ASIC1 in glioblastoma multiforme (GBM). Herein, we report that
      ASIC1 and CaMKII assemble to form a functional complex at the plasma membrane of
      GBM cells. We found that migration ability was significantly attenuated in GBM
      cells that were pre-treated with autocamtide-2-related inhibitory peptide (AIP),
      a CaMKII-specific inhibitor, or psalmotoxin 1 (PcTX-1), a selective ASIC1
      blocker. Furthermore, the inhibitory effect of AIP or PcTX-1 on migration was
      diminished when ASIC1 was knocked down in GBM cells; when ASIC1 knockdown GBM
      cells were concurrently treated with these two inhibitors, cell migration was
      slightly but significantly decreased. Using whole-cell patch-clamp recordings, we
      detected an amiloride-sensitive current in GBM cells, and this current was
      significantly inhibited by both PcTX-1 and AIP. Moreover, the magnitude of this
      current was dramatically decreased when ASIC1 was knocked down in GBM cells. The
      addition of AIP failed to further decrease the amplitude of this current. Taken
      together, these data suggest that ASIC1 and CaMKII form a functional complex in
      GBM cells. Furthermore, it can be concluded that CaMKII regulates the activity of
      ASIC1, which is associated with the ability of GBM cells to migrate.

PMID- 24100687
TI  - Implantation of a novel tissue-engineered graft in a large tendon defect
      initiated inflammation, accelerated fibroplasia and improved remodeling of the
      new Achilles tendon: a comprehensive detailed study with new insights.
AB  - We constructed a new artificial collagen-based graft as a tendon proper and
      covered it with a polydioxanone sheath. This bioimplant was tested in vitro and
      also its effectiveness was tested in a large tendon defect model in vivo. A 2-cm
      full defect in the left Achilles tendon of all animals (n = 120) was created. The
      animals were andomly divided into three groups: control (n = 40), treated with
      collagen-based graft (n = 40) and treated with collagen-Polydioxanone-based graft
      (n = 40). Clinical examination was done weekly. The animals were euthanized at 60
      and 120 days post-injury (DPI). The serum level of platelet-derived growth factor
      (PDGF) was measured. Hydroxyproline and dry matter content together with gross
      morphologic, histomorphometric, ultrastructural and biomechanical characteristics
      of the healing tissues were studied. The mechanism of host-graft interactions was
      studied in another 55 pilot animals. The graft was able to initiate inflammation,
      accelerate fibroplasia and improve remodeling of the neotenon in the defect area.
      Except for small remnants, most parts of the implants were gradually absorbed and
      substituted by a newly regenerated tendon. The preserved remnants were accepted
      as a part of neotenon and acted as scaffolds for the newly regenerated collagen
      fibrils. Unlike the controls, the treated lesions showed lower peritendinous
      adhesion, muscle fibrosis and atrophy and higher hydroxyproline concentration,
      dry matter content, ultimate strength, yield strength and modulus of elasticity.
      Numbers, diameter, density and differentiation of collagen fibrils were also
      greater in the treated lesions than the control ones. This study showed that the
      implant was cytocompatible, biodegradable, biocompatible and effective in tendon
      healing. 

PMID- 24100689
TI  - Beyond abiraterone: new hormonal therapies for metastatic castration-resistant
      prostate cancer.
AB  - Prostate cancer is a heterogeneous disease where the previous concept of "hormone
      resistance" has been changed by a new generation of hormonal therapies that have
      proven efficacy in the castration-resistant setting. The fact is that androgens
      play a crucial role in the whole clinical course of prostate cancer, even when a
      patient meets castration-resistance criteria. The development of abiraterone
      showed how important and clinically meaningful can be to achieve the lowest
      possible levels of testosterone, and androgen receptor overexpression, mutation,
      or enhanced crosstalk with other pathways, which can also be targeted with new
      agents tested in the last few years. New androgen biosynthesis inhibitors have
      been developed, such as orteronel (TAK-700), but also new antiandrogens
      (enzalutamide, ARN-509, ODM-201) or even agents with a dual mechanism of action
      (galeterone). In this review the development of new hormonal therapies following
      the arrival of abiraterone for the treatment of prostate cancer will be
      summarized. 

PMID- 24100688
TI  - Cerebral amyloid PET imaging in Alzheimer's disease.
AB  - The devastating effects of the still incurable Alzheimer's disease (AD) project
      an ever increasing shadow of burden on the health care system and society in
      general. In this ominous context, amyloid (Abeta) imaging is considered by many
      of utmost importance for progress towards earlier AD diagnosis and for potential
      development of effective therapeutic interventions. Amyloid imaging positron
      emission tomography procedures offer the opportunity for accurate mapping and
      quantification of amyloid-Abeta neuroaggregate deposition in the living brain of
      AD patients. This review analyzes the perceived value of current Abeta imaging
      probes and their clinical utilization and, based on amyloid imaging results,
      offers a hypothesis on the effects of amyloid deposition on the biology of AD and
      its progression. It also analyzes lingering questions permeating the field of
      amyloid imaging on the apparent contradictions between imaging results and known
      neuropathology brain regional deposition of Abeta aggregates. As a result, the
      review also discusses literature evidence as to whether brain Abeta deposition is
      truly visualized and measured with these amyloid imaging agents, which would have
      significant implications in the understanding of the biological AD cascade and in
      the monitoring of therapeutic interventions with these surrogate Abeta markers. 

PMID- 24100690
TI  - Cell-cell adhesion genes CTNNA2 and CTNNA3 are tumour suppressors frequently
      mutated in laryngeal carcinomas.
AB  - Laryngeal squamous cell carcinoma is a frequent and significant cause of
      morbidity and mortality. Here we explore the biological basis of this aggressive
      tumour, and identify two cell-cell adhesion genes as recurrently mutated in this
      malignancy. We first perform exome sequencing of four laryngeal carcinomas and
      their matched normal tissues. Among the 569 genes found to present somatic
      mutations, and based on their recurrence or functional relevance in cancer, we
      select 40 for further validation in 86 additional laryngeal carcinomas. We detect
      frequent mutations (14 of 90, 15%) in CTNNA2 and CTNNA3-encoding alpha-catenins.
      Functional studies reveal an increase in the migration and invasive ability of
      head and neck squamous cell carcinoma cells producing mutated forms of CTNNA2 and
      CTNNA3 or in cells where both alpha-catenins are silenced. Analysis of the
      clinical relevance of these mutations demonstrates that they are associated with
      poor prognosis. We conclude that CTNNA2 and CTNNA3 are tumour suppressor genes
      frequently mutated in laryngeal carcinomas. 

PMID- 24100691
TI  - Miniaturized self-expanding drug-eluting stent in small coronary arteries: late
      effectiveness.
AB  - BACKGROUND: Small vessels represent a risk factor for restenosis in percutaneous
      coronary angioplasty (PCA). The Sparrow(r) self-expanding drug-eluting stent,
      which has a lower profile than the current systems, has never been tested in this
      scenario. OBJECTIVES: To evaluate the late effectiveness of the Sparrow(r) drug
      eluting stent, regarding in-stent late lumen loss (LLL). METHODS: Patients with
      ischemia, symptomatic or documented, were submitted to PCA in vessels with
      reference diameter < 2.75 mm, divided into two groups regarding Sparrow(r) stent
      type: group 1: Sparrow(r) drug-eluting stent (DES), group 2: Sparrow(r) bare
      metal stent (BMS). Clinical follow-up duration was 12 months. Evaluation using
      quantitative coronary angiography (QCA) was performed immediately and at 8
      months. A decrease of over 65% of in-stent LLL with DES was estimated to
      calculate sample size. IBM(r) SPSS software, release 19 (Chicago, Illinois, USA)
      was used for the statistical analysis. RESULTS: A total of 24 patients were
      randomized, 12 in each group. The DES and BMS groups were similar in age (63.25
      +/- 10.01 vs. 64.58 +/- 11.54, p = 0.765), male gender (58.3% vs. 33.3%, p =
      0.412), risk factors and all angiographs aspects. Immediate results were
      satisfactory in both groups. At 8 months in-stent late lumen loss was
      significantly lower in DES than in BMS group (DES vs. BMS 0.25 +/- 0.16 0.97 +/-
      0.76, p = 0.008). CONCLUSION: In small-vessel PCA, the Sparrow(r) DES determined
      significant reduction in in-stent LLL, when compared to Sparrow(r) BMS.

PMID- 24100692
TI  - Criteria for mitral regurgitation classification were inadequate for dilated
      cardiomyopathy.
AB  - BACKGROUND: Mitral regurgitation (MR) is common in patients with dilated
      cardiomyopathy (DCM). It is unknown whether the criteria for MR classification
      are inadequate for patients with DCM. OBJECTIVE: We aimed to evaluate the
      agreement among the four most common echocardiographic methods for MR
      classification. METHODS: Ninety patients with DCM were included. Functional MR
      was classified using four echocardiographic methods: color flow jet area (JA),
      vena contracta (VC), effective regurgitant orifice area (ERO) and regurgitant
      volume (RV). MR was classified as mild, moderate or important according to the
      American Society of Echocardiography criteria and by dividing the values into
      terciles. The Kappa test was used to evaluate whether the methods agreed, and the
      Pearson correlation coefficient was used to evaluate the correlation between the
      absolute values of each method. RESULTS: MR classification according to each
      method was as follows: JA: 26 mild, 44 moderate, 20 important; VC: 12 mild, 72
      moderate, 6 important; ERO: 70 mild, 15 moderate, 5 important; RV: 70 mild, 16
      moderate, 4 important. The agreement was poor among methods (kappa=0.11;
      p<0.001). It was observed a strong correlation between the absolute values of
      each method, ranging from 0.70 to 0.95 (p<0.01) and the agreement was higher when
      values were divided into terciles (kappa = 0.44; p < 0.01) CONCLUSION: The use of
      conventional echocardiographic criteria for MR classification seems inadequate in
      patients with DCM. It is necessary to establish new cutoff values for MR
      classification in these patients.

PMID- 24100693
TI  - Optimized treatment and heart rate reduction in chronic heart failure.
AB  - BACKGROUND: Heart failure (HF) is a syndrome that leads to poor outcome in
      advanced forms. The neurohormonal blockade modifies this natural history;
      however, it is often suboptimal. OBJECTIVE: The aim of this study is to assess at
      what percentage cardiologists used to treating HF can prescribe target doses of
      drugs of proven efficacy. METHODS: A total of 104 outpatients with systolic
      dysfunction were consecutively enrolled, all under stabilized treatment.
      Demographic and treatment data were evaluated and the doses achieved were
      verified. The findings are shown as percentages and correlations are made between
      different variables. RESULTS: The mean age of patients was 64.1 +/- 14.2 years,
      with SBP =115.4 +/- 15.3, HR = 67.8 +/- 9.4 bpm, weight = 76.0 +/- 17.0 kg and
      sinus rhythm (90.4%). As for treatment, 93.3% received a RAS blocker (ACEI
      52.9%), all received beta-blockers (BB), the most often prescribed being
      carvedilol (92.3%). As for the doses: 97.1% of those receiving an ARB were below
      the optimal dose and of those who received ACEI, 52.7% received an optimized
      dose. As for the BB, target doses were prescribed to 76.0% of them. In this group
      of patients, most with BB target dose, it can be seen that 36.5% had HR > 70 bpm
      in sinus rhythm. CONCLUSION: Cardiologists used to treating HF can prescribe
      target doses of ACEI and BB to most patients. Even though they receive the
      recommended doses, about one third of patients persists with HR > 70 bpm and
      should have their treatment optimized.

PMID- 24100694
TI  - Antithrombotic strategy in the three first months following bioprosthetic heart
      valve implantation.
AB  - Heart valve prosthesis unquestionably improve quality of life and survival of
      patients with severe valvular heart disease, but the need for antithrombotic
      therapy to prevent thromboembolic complications is a major challenge to
      clinicians and their patients. Of the articles analyzed, most were retrospective
      series of cases or historical cohorts obtained from the database. The few
      published randomized trials showed no statistical power to assess the primary
      outcome of death or thromboembolic event. In this article, we decided to perform
      a systematic literature review, in an attempt to answer the following question:
      what is the best antithrombotic strategy in the first three months after
      bioprosthetic heart valve implantation (mitral and aortic)? After two reviewers
      applying the extraction criteria, we found 1968 references, selecting 31
      references (excluding papers truncated, which combined bioprosthesis with
      mechanical prosthesis, or without follow-up). Based on this literature review,
      there was a low level of evidence for any antithrombotic therapeutic strategy
      evaluated. It's therefore interesting to use aspirin 75 to 100 mg / day as
      antithrombotic strategy after bioprosthesis replacement in the aortic position,
      regardless of etiology, for patients without other risk factors such as atrial
      fibrillation or previous thromboembolic event. In the mitral position, the risk
      of embolism, although low, is more relevant than in the aortic position,
      according to published series and retrospective cohorts comprised mostly of
      elderly non-rheumatic patients. 

PMID- 24100695
TI  - Mortality impact of thoracic aortic disease in Sao Paulo state from 1998 to 2007.
AB  - BACKGROUND: The epidemiological characteristics of thoracic aortic diseases (TAD)
      in the State of Sao Paulo and in Brazil, as well as their impact on the survival
      of these patients have yet to be analyzed. OBJECTIVES: To evaluate the mortality
      impact of TAD and characterize it epidemiologically. METHODS: Retrospective
      analysis of data from the public health system for the TAD registry codes of
      hospitalizations, procedures and deaths, from the International Code of Diseases
      (ICD-10), registered at the Ministry of Health of Sao Paulo State from January
      1998 to December 2007. RESULTS: They were 9.465 TAD deaths, 5.500 men (58.1%) and
      3.965 women (41.9%); 6.721 dissections (71%) and 2.744. aneurysms. In 86.3% of
      cases the diagnosis was attained during autopsy. There were 6.109
      hospitalizations, of which 67.9% were males; 21.2% of them died (69% men), with
      similar proportions of dissection and aneurysm between sexes, respectively 54%
      and 46%, but with different mortality. Men with TAD die more often than women (OR
      = 1.5). The age distribution for deaths and hospitalizations was similar with
      predominance in the 6th decade. They were 3.572 surgeries (58% of
      hospitalizations) with 20.3% mortality (patients kept in clinical treatment
      showed 22.6% mortality; p = 0.047). The number of hospitalizations, surgeries,
      deaths of in-patients and general deaths by TAD were progressively greater than
      the increase in population over time. CONCLUSIONS: Specific actions for the early
      identification of these patients, as well as the viability of their care should
      be implemented to reduce the apparent progressive mortality from TAD seen among
      our population.

PMID- 24100696
TI  - Physician assistants-a brand you can trust.

PMID- 24100697
TI  - It is not too late to remember our roots.

PMID- 24100698
TI  - Cost-effectiveness decision making and US public opinion.

PMID- 24100699
TI  - Thin-film microfabricated nanofluidic arrays for size-selective protein
      fractionation.
AB  - Size-selective fractionation and quantitation of biostructures in the sub-hundred
      nanometer size range is an important research area. Unfortunately, current
      methods for size fractionation are complex, time consuming, or offer poor
      resolution. Using standard microfabrication technology, we developed a
      nanofluidic sieving system to address these limitations. Our setup consists of an
      array of parallel nanochannels with a height step in each channel, an injection
      reservoir, and a waste reservoir. The height steps can size fractionate a protein
      mixture as a solution flows through the nanochannels via capillary action. We
      tested this system with different sizes and concentrations of five proteins to
      understand protein size and height step effects on trapping. Our results clearly
      show size-dependent trapping of proteins at nanometer-scale height steps in
      nanochannels. We also developed a model that predicts the observed size-dependent
      trapping of proteins. This work is a key step towards scalable nanofluidic
      methods for molecular fractionation. 

PMID- 24100700
TI  - [For and against: psychotherapeutical treatment of mild depression].

PMID- 24100701
TI  - Serological investigation of rabies virus neutralizing antibodies in bats
      captured in the eastern Brazilian Amazon.
AB  - BACKGROUND: In 2004 and 2005 a total of 38 cases of human rabies transmitted by
      the hematophagous bat Desmodus rotundus were registered in the Brazilian state of
      Para; 23 (60.5%) cases occurred in the northeastern region. Because of this, a
      serological investigation for the antibodies of rabies virus was performed in
      municipalities of the northeastern state of Para, in order to assess whether the
      virus was circulating among different bat species. METHODS: Bats were collected
      in 2009 with mist-nets during the rainy and dry seasons and blood samples were
      collected for the serological survey. RESULTS: A total of 307 serum samples were
      obtained representing 28 bat species. The number of seropositives was high
      (50.8%, 156/307) and was significantly higher during the rainy season (67.4%,
      95/141). No significant difference in rates was found between male and female or
      adult and juvenile. Seropositive individuals were recorded in 24 species sampled,
      the most prominent being Artibeus planirostris, with 52.2% (24/46) positive
      individuals. CONCLUSION: The serological proportion reported in this paper in a
      large numbers of individuals indicates that the rabies virus circulates quite
      actively in the study region, but, because of the production of antibodies, the
      expression of the disease in these individuals is low.

PMID- 24100702
TI  - In-flight gas phase growth of metal/multi layer graphene core shell nanoparticles
      with controllable sizes.
AB  - In this report, we present a general method for a continuous gas-phase synthesis
      of size-selected metal/multi layer graphene (MLG) core shell nanoparticles having
      a narrow size distribution of metal core and MLG shell for direct deposition onto
      any desired substrate kept under clean vacuum conditions. Evolution of MLG
      signature is clearly observed as the metal-carbon agglomerates get transformed to
      well defined metal/MLG core shell nanoparticles during their flight through the
      sintering zone. The growth takes place via an intermediate state of alloy
      nanoparticle (Pd-carbon) or composite nanoparticle (Cu-carbon), depending upon
      the carbon solubility in the metal and relative surface energy values. It has
      been also shown that metal/MLG nanoparticles can be converted to graphene shells.
      This study will have a large impact on how graphene or graphene based composite
      nanostructures can be grown and deposited in applications requiring controllable
      dimensions, varied substrate choice, large area and large scale depositions. 

PMID- 24100704
TI  - Changes of proteome components of Helicobacter pylori biofilms induced by serum
      starvation.
AB  - Biofilm is the adaptive living mechanism of Helicobacter pylori (H. pylori)
      during survival and propagation. Nutrient starvation is an environmental pressure
      for H. pylori in vivo and in vitro. Serum starvation effectively mimics the
      microenvironment in which H. pylori colonizes healthy humans who carry H. pylori
      and patients with chronic atrophic gastritis. In addition, it also mimics the in
      vitro environmental pressures of H. pylori. An H. pylori biofilm was successfully
      induced with serum starvation. To identify novel proteins associated with biofilm
      formation at the early stage in H. pylori, high-resolution 2-dimensional gel
      electrophoresis was performed to obtain the proteome profiles of spiral H. pylori
      and early biofilm. Differential protein spots were identified using tandem matrix
      assisted laser desorption ionization time of flight mass spectrometry, which
      revealed 35 proteins. These proteins are associated with various biological
      functions, including flagellar movement, bacterial virulence, signal transduction
      and regulation. To verify the results, the expression of cagA at the mRNA and
      protein levels was examined by fluorescence quantitative PCR and western blot
      analysis, respectively. This study indicates that H. pylori form biofilms by
      initiating multiple mechanisms involving a number of signaling pathways.

PMID- 24100705
TI  - Pain course in conservatively treated patients with back pain and a VCF on the
      spine radiograph (VERTOS III).
AB  - OBJECTIVE: Little is known about the natural course of pain from vertebral
      compression fractures (VCF). In this study we evaluated the pain course in
      conservatively treated patients with back pain and a VCF on the spine radiograph.
      MATERIALS AND METHODS: Between May 2007 and November 2008, 169 patients with back
      pain referred by the general practitioner for spine radiographs and with a VCF
      were requested to participate in this follow-up study. Base line questionnaires
      about visual analogue scale (VAS) score, type of treatment and use of
      osteoporosis medication were filled in by 82 patients. Questionnaires were
      repeated at 6 weeks, and at 3, 6 and 12 months. Significant pain relief was
      defined as a decrease in VAS score of 50% or more from baseline. RESULTS: At
      baseline, mean VAS score in 82 patients was 6.9 (SD 2.0). Significant pain relief
      at 12 months was reported by 44 patients (54%) while in 38 patients (46%) pain
      relief was insufficient. No predictors for pain relief could be identified.
      Patients with insufficient pain relief at 12 months used significantly more
      analgesics and in these patients physiotherapy did better than other types of
      therapy. CONCLUSION: More than half of conservatively treated patients with back
      pain and VCF had sufficient pain relief at 12 months with most pain decrease in
      the first 3 months. However, a substantial proportion of patients still reported
      disabling pain. There were no predictors for the development of chronic pain.
      Patients with continuing pain >=3 months after diagnosis of VCF may be candidates
      for vertebroplasty.

PMID- 24100703
TI  - AMP-activated protein kinase (AMPK) beyond metabolism: a novel genomic stress
      sensor participating in the DNA damage response pathway.
AB  - AMP-activated protein kinase (AMPK), an established metabolic stress sensor, has
      gained popularity in cancer biology due to its ability to control cellular growth
      and mediate cell cycle checkpoints in cancer cells in response to low energy
      levels. AMPK is a key effector of the tumor suppressor liver kinase B 1 (LKB1)
      which inhibits the cellular growth mediator mammalian target of rapamycin (mTOR)
      and activates checkpoint mediators such as p53 and the cyclin dependent kinase
      inhibitors p21(cip1) and p27(kip1). However, recent work describes a novel
      function for AMPK as a sensor of genomic stress and a participant of the DNA
      damage response (DDR) pathway. Ionizing radiation and chemotherapy activate AMPK
      in cancer cells to mediate signal transduction downstream of ataxia
      telangiectasia mutated (ATM) to activate p53- p21(cip1)/p27(kip1) and inhibit
      mTOR. We discuss evidence on the transcriptional and post-translational
      regulation of AMPK by ionizing radiation and the role of the enzyme as a mediator
      of chemo- and radiation sensitivity in epithelial cancer cells. Furthermore, we
      review data on the participation of AMPK in cytokinesis and observations
      suggesting a physical association of this enzyme with the mitotic apparatus. The
      evidence available to date suggests that AMPK is a point of convergence of
      metabolic and genomic stress signals, which (1) control the activity of growth
      mediators, (2) propagate DDR, and (3) mediate the anti-proliferative effects of
      common cytotoxic cancer therapy such as radiation and chemotherapy. This
      highlights the importance of targeting AMPK with novel cancer therapeutics. 

PMID- 24100706
TI  - Multi-detector thoracic CT findings in cerebro-costo-mandibular syndrome: rib
      gaps and failure of costo-vertebral separation.
AB  - Cerebro-costo-mandibular syndrome (CCMS) describes a triad of mandibular
      hypoplasia, brain dysfunction and posterior rib defects ("rib gaps"). We present
      the CT imaging for a 2-year-old girl with CCMS that highlights the rib gap
      defects and shows absent transverse processes with abnormal fusion of the ribs
      directly to the vertebral bodies. We argue that this is likely to relate to
      abnormal lateral sclerotome development in embryology, with the failure of normal
      costo-vertebral junctions compounding impaired thoracic function. The case also
      highlights the use of CT for specific indications in skeletal dysplasia. 

PMID- 24100707
TI  - Fibroma of the tendon sheath of the long head of the biceps tendon.
AB  - Fibroma of the tendon sheath is a benign tumor that is less common than giant
      cell tumor of the tendon sheath. Both tumors may present as a painless, slowly
      enlarging mass. Radiological findings may be similar for both tumors.
      Histologically, fibroma of the tendon sheath lacks the hemosiderin-laden
      macrophages that are typical for giant cell tumor of the tendon sheath. We report
      on a 49-year-old woman with fibroma of the tendon sheath of the long head of the
      biceps tendon. In our case, on MR images, we observed band-like hypointense areas
      centrally in the tumor, mild patchy contrast enhancement, and most importantly,
      no decrease of signal intensity on gradient echo images. These characteristics
      reflected histological findings. 

PMID- 24100708
TI  - Correlation of spectral domain optical coherence tomography findings and visual
      acuity in central serous chorioretinopathy.
AB  - PURPOSE: To investigate the correlation between spectral domain optical coherence
      tomography findings and best-corrected visual acuity (BCVA) in patients with
      central serous chorioretinopathy (CSC) and to determine the visual prognostic
      factors. METHODS: We retrospectively studied 56 eyes of 49 patients who had the
      diagnosis of CSC. Patients were categorized into subgroups depending on symptoms
      and clinical findings. Together with the overall foveal integrity of inner
      segment/outer segment (IS/OS) and external limiting membrane, several features of
      CSC including hyperreflective dots and hypertrophy of retinal pigment epithelium
      were investigated with spectral domain optical coherence tomography. Thickness
      measurements within the retina and choroid were performed. RESULTS: Best
      corrected visual acuity was closely associated with IS/OS line integrity (P <
      0.001). The length of IS/OS disruption also had significant correlation with BCVA
      (r = -0.324, P = 0.016). Loss of foveal IS/OS and external limiting membrane line
      integrity was related to low BCVA (P < 0.001 for both). Presence of
      hyperreflective dots (P < 0.001) and retinal pigment epithelium hypertrophy (P =
      0.011) had significant association with visual status. In cases with sequelae of
      CSC, BCVA was correlated with parameters of outer retinal damage. CONCLUSION:
      Besides the overall integrity of IS/OS line and the length of disruption, loss of
      foveal IS/OS and external limiting membrane integrity are also noteworthy in
      cases with CSC. Hyperreflective dots and retinal pigment epithelium hypertrophy
      are closely associated with BCVA in cases with CSC. Analysis of the subgroups has
      shown that morphologic changes that persist until the late phases of the disease
      could potentially affect the visual outcome.

PMID- 24100709
TI  - Incidence and characteristics of neovascularization in fellow eyes of Japanese
      patients with unilateral retinal angiomatous proliferation.
AB  - PURPOSE: To describe the incidence and characteristics of neovascularization in
      fellow eyes of Japanese patients with unilateral retinal angiomatous
      proliferation (RAP). METHODS: We retrospectively studied patients with unilateral
      RAP in one center between 2003 and 2010. The minimal follow-up time was 2 years.
      The prevalence rates of soft drusen and reticular pseudodrusen in the fellow eyes
      at the first visit were examined in color fundus photographs and optical
      coherence tomography images. Stepwise analysis was performed to identify a
      correlation between the incidence of RAP in the fellow eyes and age, gender,
      follow-up time, soft drusen, and reticular pseudodrusen. RESULTS: Twenty eyes
      were included in this study. The mean follow-up time was 49 months (range, 24-108
      months). At the first visit, soft drusen was seen in 19 eyes (95%) and reticular
      pseudodrusen in 11 eyes (55%). Neovascular age-related macular degeneration
      developed in 10 eyes, including RAP in 9 eyes (45%) and polypoidal choroidal
      vasculopathy in 1 eye (5%). Stepwise analysis showed that reticular pseudodrusen
      and longer follow-up time were correlated significantly (P = 0.0384 and P =
      0.0341, respectively) with the incidence of RAP. CONCLUSION: Bilateral RAP
      developed in almost half of the eyes initially diagnosed with unilateral RAP and
      the incidence increased with time. Reticular pseudodrusen is a risk factor for
      bilateral RAP.

PMID- 24100710
TI  - The effect of word familiarity on actual and perceived text difficulty.
AB  - There is little evidence that readability formula outcomes relate to text
      understanding. The potential cause may lie in their strong reliance on word and
      sentence length. We evaluated word familiarity rather than word length as a stand
      in for word difficulty. Word familiarity represents how well known a word is, and
      is estimated using word frequency in a large text corpus, in this work the Google
      web corpus. We conducted a study with 239 people, who provided 50 evaluations for
      each of 275 words. Our study is the first study to focus on actual difficulty,
      measured with a multiple-choice task, in addition to perceived difficulty,
      measured with a Likert scale. Actual difficulty was correlated with word
      familiarity (r=0.219, p<0.001) but not with word length (r=-0.075, p=0.107).
      Perceived difficulty was correlated with both word familiarity (r=-0.397,
      p<0.001) and word length (r=0.254, p<0.001). 

PMID- 24100711
TI  - The potential of the human immune system to develop broadly neutralizing HIV-1
      antibodies: implications for vaccine development.
AB  - OBJECTIVES AND DESIGN: Developing an effective HIV-1 vaccine that elicits broadly
      neutralizing HIV-1 human antibodies (bnAbs) remains a challenging goal. Extensive
      studies on HIV-1 have revealed various strategies employed by the virus to escape
      host immune surveillance. Here, we investigated the human antibody gene
      repertoires of uninfected and HIV-1-infected individuals at genomic DNA (gDNA)
      and cDNA levels by deep sequencing followed by high-throughput sequence analysis
      to determine the frequencies of putative germline antibody genes of known HIV-1
      monoclonal bnAbs (bnmAbs). METHODS: Combinatorial gDNA and cDNA antibody
      libraries were constructed using the gDNAs and mRNAs isolated from uninfected and
      HIV-1-infected human peripheral blood mononuclear cells (PBMCs). All libraries
      were deep sequenced and sequences analysed using IMGT/HighV-QUEST software
      (http://imgt.org/HighV-QUEST/index.action). The frequencies of putative germline
      antibodies of known bnmAbs in the gDNA and cDNA libraries were determined.
      RESULTS AND CONCLUSION: The human gDNA antibody libraries were more diverse in
      heavy and light chain V-gene lineage usage than the cDNA libraries, indicating
      that the human gDNA antibody gene repertoires may have more potential than the
      cDNA repertoires to develop HIV-1 bnAbs. The frequencies of the heavy and kappa
      and lambda light chain variable regions with identical V(D)J recombinations to
      known HIV-1 bnmAbs were extremely low in human antibody gene repertoires.
      However, we found relatively high frequencies of the heavy and kappa and lambda
      light chain variable regions that used the same V-genes and had the same CDR3
      lengths as known HIV-1 bnmAbs regardless of (D)J-gene usage. B-cells bearing B
      cell receptors of such heavy and kappa and lambda light chain variable regions
      may be stimulated to induce HIV-1 bnAbs.

PMID- 24100712
TI  - Water, sanitation, and hygiene interventions to improve health among people
      living with HIV/AIDS: a systematic review.
AB  - DESIGN: People living with HIV/AIDS (PLHIV) are at increased risk of diarrhoeal
      disease and enteric infection. This review assesses the effectiveness of water,
      sanitation, and hygiene (WASH) interventions to prevent disease among PLHIV.
      METHODS: We searched MEDLINE, EMBASE, Global Health, The Cochrane Library, Web of
      Science, LILACS, Africa-wide, IMEMR, IMSEAR, WPRIM, CNKI, and WanFang. We also
      hand searched conference proceedings, contacted researchers and organizations,
      and checked references from identified studies. Eligible studies were those
      involving WASH interventions among PLHIV that reported on health outcomes and
      employed a controlled study design. We extracted data, explored heterogeneity,
      sub-grouped based on outcomes, calculated pooled effects on diarrhoeal disease
      using meta-analysis, and assessed studies for methodological quality. RESULTS:
      Ten studies met the eligibility criteria and are included in the review, of which
      nine involved water quality interventions and one involved promotion of
      handwashing. Among eight studies that reported on diarrhoea, water quality
      interventions (seven studies, pooled RR = 0.57, 95% CI: 0.38-0.86) and the
      handwashing intervention (one study, RR = 0.42, 95% CI: 0.33-0.54) were
      protective against diarrhoea. One study reported that household water treatment
      combined with insecticide treated bednets slowed the progression of HIV/AIDS. The
      validity of most studies is potentially compromised by methodological
      shortcomings. CONCLUSION: No studies assessed the impact of improved water supply
      or sanitation, the most fundamental of WASH interventions. Despite some evidence
      that water quality interventions and handwashing are protective against
      diarrhoea, substantial heterogeneity and the potential for bias raise questions
      about the actual level of protection.

PMID- 24100713
TI  - Infection duration and inflammatory imbalance are associated with atherosclerotic
      risk in HIV-infected never-smokers independent of antiretroviral therapy.
AB  - OBJECTIVES: To determine whether the reported increased atherosclerotic risk
      among HIV-infected individuals is related to antiretroviral therapy (ART) or HIV
      infection, whether this risk persists in never-smokers, and whether inflammatory
      profiles are associated with higher risk. DESIGN: Matched cross-sectional study.
      METHODS: A total of 100 HIV-infected patients (50 ART-treated >4 years, 50 ART
      naive but HIV-infected >2 years) and 50 HIV-negative controls were recruited in
      age-matched never-smoking male triads (mean age 40.2 years). Carotid intima-media
      maximal thickness (c-IMT) was measured across 12 sites. Pro-inflammatory [highly
      sensitive C-reactive protein (hs-CRP), resistin, interleukin-6, interleukin-18,
      insulin, serum amyloid A, D-dimer) and anti-inflammatory (total and high
      molecular weight adiponectin, interleukin-27, interleukin-10) markers were
      dichotomized into high/low scores (based on median values). c-IMT was compared
      across HIV/treatment groups or inflammatory profiles using linear regression
      models adjusted for age, diabetes, hypertension, and, for HIV-infected patients,
      nadir CD4 cell counts. RESULTS: Although adjusted c-IMT initially tended to be
      thicker in ART-exposed patients (P=0.2), in post-hoc analyses stratifying by
      median HIV duration we observed significantly higher adjusted c-IMT in patients
      with longer (>7.9 years: 0.760+/-0.008 mm) versus shorter prevalent duration of
      known HIV infection (<7.9 years: 0.731+/-0.008 mm, P=0.02), which remained
      significant after additionally adjusting for ART (P=0.04). Individuals with low
      anti-inflammatory profile (<median versus >median score) had thicker c-IMT
      (0.754+/-0.006mm versus 0.722+/-0.006 mm, P<0.001), with anti-inflammatory
      markers declining as prevalent duration of HIV infection increased (P for linear
      trend <0.001). CONCLUSION: Known HIV duration is related to thicker c-IMT,
      irrespective of ART, in these carefully selected age-matched never-smoking HIV
      treated and ART-naive male individuals. Higher levels of anti-inflammatory
      markers appeared protective for atherosclerosis.

PMID- 24100714
TI  - Falling threshold for treatment of borderline elevated thyrotropin levels
      balancing benefits and risks: evidence from a large community-based study.
AB  - IMPORTANCE: Rates of thyroid hormone prescribing in the United States and the
      United Kingdom have increased substantially. If some of the increase is due to
      lowering the thyrotropin threshold for treatment, this may result in less benefit
      and greater harm. OBJECTIVE: To define trends in thyrotropin levels at the
      initiation of levothyroxine sodium therapy and the risk of developing a
      suppressed thyrotropin level following treatment. DESIGN, SETTING, PARTICIPANTS,
      AND EXPOSURE: Retrospective cohort study using data from the United Kingdom
      Clinical Practice Research Datalink. Among 52,298 individuals who received a
      prescription for levothyroxine between January 1, 2001, and October 30, 2009, we
      extracted data about the thyrotropin level before levothyroxine therapy
      initiation, clinical symptoms, and thyrotropin levels up to 5 years after
      levothyroxine was initiated. We excluded persons who had a history of
      hyperthyroidism, pituitary disease, or thyroid surgery; those who were taking
      thyroid-altering medication or if the levothyroxine prescription was related to
      pregnancy; and those who did not have a thyrotropin level measured within 3
      months before the initiation of levothyroxine. MAIN OUTCOMES AND MEASURES: The
      median thyrotropin level at the time of the index levothyroxine prescription, the
      odds of initiation of levothyroxine therapy at thyrotropin levels of 10.0 mIU/L
      or less, and the age-stratified odds of developing a low or suppressed
      thyrotropin level after levothyroxine therapy. RESULTS: Between 2001 and 2009,
      the median thyrotropin level at the initiation of levothyroxine therapy fell from
      8.7 to 7.9 mIU/L. The odds ratio for prescribing levothyroxine at thyrotropin
      levels of 10.0 mIU/L or less in 2009 compared with 2001 (adjusted for changes in
      population demographics) was 1.30 (95% CI, 1.19-1.42; P < .001). Older
      individuals and individuals with cardiac risk factors had higher odds of
      initiation of levothyroxine therapy with a thyrotropin level 10.0 mIU/L or less.
      At 5 years after levothyroxine initiation, 5.8% of individuals had a thyrotropin
      level of <0.1 mIU/L. Individuals with depression or tiredness at baseline had
      increased odds of developing a suppressed thyrotropin level, whereas individuals
      with cardiac risk factors (eg, atrial fibrillation, diabetes mellitus,
      hypertension, and raised lipid levels) did not. CONCLUSIONS AND RELEVANCE: We
      observed a trend toward levothyroxine treatment of more marginal degrees of
      hypothyroidism and a substantial risk of developing a suppressed thyrotropin
      level following therapy. Large-scale prospective studies are required to assess
      the risk-benefit ratio of current practice.

PMID- 24100715
TI  - Bariatric procedures: an update on techniques, outcomes and complications.
AB  - PURPOSE OF REVIEW: Obesity is a rising epidemic, and it is projected that over
      700 million people will be obese by 2015. As the number of people with morbid
      obesity rises, so will the number of bariatric procedures performed. The goal of
      this article is to review current surgical and endoscopic options for weight loss
      in morbidly obese patients including their efficacy and complications. RECENT
      FINDINGS: New bariatric surgical techniques have been developed with the goals of
      maximizing weight loss and metabolic outcomes, while minimizing complications. In
      addition, there is a role for therapeutic endoscopy in treating obesity as well
      as managing bariatric surgical complications. As the metabolic effects of
      bariatric surgery are better elucidated, bariatric surgeries may provide a role
      in treatment of metabolic syndrome in mildly obese individuals. For those with
      insufficient weight loss, revisional bariatric surgeries have been performed with
      varying success. SUMMARY: Bariatric surgery is an effective treatment for obesity
      and its comorbidities. Several bariatric surgeries are available, and a
      multidisciplinary approach is recommended for choosing the best procedure for the
      appropriate candidate, along with providing long-term follow-up care to maximize
      outcome.

PMID- 24100716
TI  - Regulatory cell populations in the intestinal mucosa.
AB  - PURPOSE OF REVIEW: The purpose of this review is to summarize recent advances in
      the fields of intestinal T-regulatory cell (Treg) and tolerogenic dendritic cell
      subsets. Under homeostatic conditions, CD4(+) Tregs and tolerogenic dendritic
      cells function to maintain mucosal tolerance. Loss of immune homeostasis is the
      primary cause of intestinal abnormalities, including inflammatory bowel disease.
      Thus, an improved understanding of cellular mechanisms promoting tolerance will
      be critical for the development of more efficacious therapies to treat chronic
      intestinal inflammation. RECENT FINDINGS: Significant progress has been made in
      the past year in the study of mucosal Treg and dendritic cell populations. In
      particular, efforts have focused on the migration and differentiation of these
      cells in the intestinal mucosa, the functional consequences of cross-talk with
      the intestinal microbiome, mechanisms by which tolerogenic dendritic cells take
      up antigen, and regulation of retinoic acid synthesis. SUMMARY: Recent studies
      examining tolerogenic cell populations of the intestinal mucosa highlight the
      progress in understanding the function, regulation, and cross-talk of Treg and
      dendritic cell populations, and their interactions with the gut microbiota.
      Scientific advances in these areas will undoubtedly lead to the development of
      more effective therapeutic strategies for intestinal abnormalities such as
      inflammatory bowel disease.

PMID- 24100717
TI  - Faecal microbiota transplantation for the treatment of recurrent Clostridium
      difficile infection: current promise and future needs.
AB  - PURPOSE OF REVIEW: The use of faecal microbiota transplantation (FMT) as
      treatment for recurrent Clostridium difficile infection (CDI) has increased
      rapidly over the past few years. In this review, we highlight clinical studies of
      FMT for treatment of recurrent CDI and discuss the safety, standardization and
      future of this treatment option. The major risk factor for CDI is prior
      antibiotic use, which results in an altered state of the gut microbiota
      characterized by decreased microbial diversity. This altered gut microbiota
      increases the patient's susceptibility to CDI. In patients with recurrent CDI,
      the microbiota remains in a state with decreased diversity, and FMT from a
      healthy individual restores the gut microbiota and subsequently colonization
      resistance against the pathogen. RECENT FINDINGS: Recent studies have shown the
      success rate for FMT as treatment for recurrent CDI being greater than 90%.
      Standardized, frozen preparations of faeces can be used, which increases the
      availability of faeces for FMT and decreases the cost of screening individual
      donors. In addition, there have been recent advances in identifying a defined
      microbial community isolated from faeces that can restore colonization resistance
      against C. difficile. SUMMARY: The use of FMT is a successful treatment for
      recurrent CDI when primary treatment options have failed. However, more work
      needs to define potential long-term consequences of this treatment and understand
      how specific members of the gut microbiota can restore colonization resistance
      against C. difficile.

PMID- 24100718
TI  - Innate lymphoid cells in homeostasis, infection, chronic inflammation and tumors
      of the gastrointestinal tract.
AB  - PURPOSE OF REVIEW: To highlight the functions of a recently discovered group of
      immune cells known as innate lymphoid cells (ILCs) during homeostasis and
      infections of the gastrointestinal tract. RECENT FINDINGS: ILCs are lymphocytes
      that lack specific antigen receptors. They are found in the mucosae and mucosal
      associated lymphoid tissues, where they promptly initiate cytokine responses to
      pathogens upon initial exposure. ILCs have been classified into distinct groups
      based on their cytokine secretion: ILC1 produce IFN-gamma, ILC2 secrete IL-5 and
      IL-13, and ILC3 produce IL-22 and IL-17. Recent studies have discovered the
      heterogeneity of ILC1 and ILC3 in the gastrointestinal tract. ILC1 subsets may
      contribute to the inflammatory bowel disease. ILC3 subsets may be beneficial in
      the defense against gastrointestinal infections, but their sustained activation
      may lead to cancer. SUMMARY: ILCs may provide a target for new avenues of
      therapeutic intervention in inflammatory bowel disease and gastrointestinal
      cancer.

PMID- 24100719
TI  - Autophagy at the crossroads of metabolism and cellular defense.
AB  - PURPOSE OF REVIEW: From its initial description as a homeostatic process required
      for starvation response, autophagy has emerged as a ubiquitous cellular process
      involved in a broad range of cellular activities from metabolic adaptation to
      cellular defense against invading pathogens. This review provides an overview of
      autophagy and highlights the recent developments in deciphering its role in
      metabolic adaptation and its importance in antibacterial defense with attention
      to regulatory pathways. RECENT FINDINGS: Within the last 2 years, there has been
      significant progress in deciphering the mechanisms by which autophagy is
      regulated, including subcellular localization, posttranslational modifications,
      and transcriptional control. In addition, the cell type-specific role of
      autophagy in maintaining cellular homeostasis has been defined, including its
      role in handling intracellular pathogens and its contribution to inflammatory
      bowel disease. SUMMARY: Autophagy is a critical pathway that integrates numerous
      regulatory inputs to maintain cellular homeostasis and defend against
      intracellular pathogens.

PMID- 24100720
TI  - Molecular signatures for the dynamic process of establishing intestinal host
      microbial homeostasis: potential for disease diagnostics?
AB  - PURPOSE OF REVIEW: The dynamic interplay of the intestinal microbiota and host
      has been the focus of many studies because of its impact on the health status in
      human life. Recent reports on the time-resolved immune and metabolic interactions
      between the host and microbiota, as well as the molecular signatures that mark
      this communication during the process of establishing a host-microbial
      relationship, are addressed here. RECENT FINDINGS: During microbial colonization,
      the progressive impact of de-novo introduction of the gut microbiota on the
      host's physiology is tightly controlled by highly intertwined regulatory networks
      and achieves an efficient and balanced interplay between the host and its
      developing microbial community. Recent findings from germ-free mouse models have
      unravelled core transcriptional, metabolic and microbial signatures, which are
      proposed to orchestrate the molecular responses during the establishment of the
      multifaceted state of intestinal host-microbe homeostasis. SUMMARY: Exploring the
      time-resolved dynamics of the host responses to the newly colonizing gut
      microbiota provides mechanistically critical understanding of the sequential host
      microbe response cascades that lead to a homeostatic relationship. Thereby, these
      approaches can provide novel diagnostic tools and therapeutic targets, or either
      of the two, in humans for specific disorders associated with intestinal dysbiosis
      and loss of homeostasis.

PMID- 24100721
TI  - Advances in therapeutic interventions targeting the vascular and lymphatic
      endothelium in inflammatory bowel disease.
AB  - PURPOSE OF REVIEW: The review summarizes the current knowledge of the roles
      played by the vascular and lymphatic endothelium throughout the gut in the
      pathogenesis of inflammatory bowel disease (IBD) and gives an update on emerging
      strategies targeting both vasculatures. RECENT FINDINGS: Enormous efforts have
      been made to understand the mechanisms underlining the origin, development and
      maintenance of intestinal chronic inflammation. In particular, new studies
      focused their attention on the role played by the microvascular and lymphatic
      endothelium in the pathogenesis of IBD. During inflammation, whereas the
      microvasculature is responsible for the entry and distribution of immune cells in
      the mucosa, the lymphatic system controls leukocyte exit, bacterial clearance and
      edema absorption. The study of these events, which are aberrant during chronic
      inflammation, has resulted in the identification and validation of several
      targets for the treatment of experimental colitis, some of which have translated
      into effective treatments for patients with IBD. SUMMARY: Although much attention
      has been paid to the microvascular endothelium and to antiangiogenic therapies,
      specific studies on the lymphatic vasculature and its functions in IBD are still
      at the initial stage, and other molecular mechanisms, genes, molecules and new
      pathways must definitely be explored.

PMID- 24100722
TI  - Nutrition, microbiomes, and intestinal inflammation.
AB  - PURPOSE OF REVIEW: To present and evaluate the recent findings that contribute to
      our understanding of the functional impact of diet on the enteric microbiome and
      outcomes of disease. RECENT FINDINGS: Nutrients in excess and in deficiency have
      significant impact on gut microbial communities in both rodents and humans,
      acting directly on the microbiota or indirectly via altering host physiology.
      Furthermore, the effects of diet on the microbiome in determining health or
      disease can differ substantially depending on the age and environment of the
      individual. SUMMARY: Dietary compounds can have profound short-term and long-term
      effects on the assemblage of the gut microbiome, which in turn affects the host
      microbe interactions critically important for intestinal, metabolic, and immune
      homeostasis. Until recently, the mechanisms underlying these effects were poorly
      understood. However, new insights have now been gained, made possible through the
      application of advanced technologies and bioinformatics, novel experimental
      models, and human research. As a result, our conceptual framework for
      understanding the impact of diet on the gut microbiome, health, and disease has
      advanced considerably, bringing the promise of better tools of risk assessment,
      diagnostics, and therapeutic intervention in an age of personalized medicine.

PMID- 24100723
TI  - The tumor necrosis factor-like cytokine 1A/death receptor 3 cytokine system in
      intestinal inflammation.
AB  - PURPOSE OF REVIEW: Tumor necrosis factor (TNF)-like cytokine 1A (TL1A) associates
      with the death receptor 3 (DR3) on activated lymphocytes and induces
      proinflammatory signals. The decoy receptor 3 (DcR3) competes for TL1A binding
      and inhibits functional signaling. This review focuses on the role of the
      TL1A/DR3/DcR3 cytokine system in inflammatory bowel diseases (IBDs). RECENT
      FINDINGS: TL1A may induce IFN-gamma-mediated and IL-17-mediated proinflammatory
      pathways in IBDs by acting on DR3-expressing, CD4(+)CD161(+) lymphocytes, which
      are substantially enriched at the inflamed intestinal mucosa. In addition,
      TL1A/DR3 signaling results in expansion of the Treg pool with concomitant and
      transient inhibition of their suppressive function. Constitutive expression of
      TL1A in transgenic mice was associated with small intestinal inflammation, which
      was accompanied by colonic fibrosis both spontaneously and under colitogenic
      conditions. Recent human studies demonstrated that soluble TL1A and DcR3 are
      present in the systemic circulation in patients with active IBD and decline after
      successful anti-inflammatory treatment. SUMMARY: TL1A/DR3 interactions may
      participate in the pathogenesis of chronic intestinal inflammation and offer
      novel therapeutic targets for patients with ulcerative colitis and Crohn's
      disease.

PMID- 24100724
TI  - Novel anticoagulants: bleeding risk and management strategies.
AB  - PURPOSE OF REVIEW: To quantify the novel oral anticoagulant (NOAC)-related
      gastrointestinal bleeding, summarize the management strategies and highlight the
      knowledge gaps. RECENT FINDINGS: Dabigatran, rivaroxaban and apixaban differ from
      warfarin with their fixed oral dose and no requirement for routine monitoring.
      Patients at highest risk of thromboembolism benefit most from NOACs; however,
      there is a clinically significant risk for NOAC-related gastrointestinal
      bleeding. The management of NOACs in the acute and elective setting differs from
      that used with warfarin. SUMMARY: The magnitude of gastrointestinal risk is still
      unclear because of paucity of literature. Current risk-stratification models are
      incomplete and cannot be used solely to predict future risk. The periendoscopic
      management requires an understanding of drug half-life, metabolism and patient's
      ability to excrete the agent. Acute bleeding management relies on fluid
      resuscitation to promote renal excretion of active metabolite, withholding the
      doses and timely management of endoscopic stigmata. The administration of
      coagulation factors (fresh frozen plasma, prothrombin complex concentrates or
      recombinant activated FVII) is more successful in reversing the activity of the
      upstream inhibitors of coagulation (rivaroxaban and apixaban) than dabigatran
      which is a direct thrombin inhibitor.

PMID- 24100725
TI  - Gastroduodenal mucosal defense.
AB  - PURPOSE OF REVIEW: To review recent developments in the field of gastroduodenal
      mucosal defense. RECENT FINDINGS: Research in the field of gastroduodenal mucosal
      defense has focused on continued elucidation of molecular mechanisms that protect
      the mucosa and influence healing at the cellular level. Review of literature over
      the past year reveals focus on familiar processes such as superoxide dismutase,
      nitric oxide, heme oxygenase-1, neutrophil infiltration, cysteamine, mucin,
      hydrogen sulfide, ghrelin, adiponectin and the influence of Helicobacter pylori,
      but also brings into light new processes such as the balance between apoptosis
      and cellular proliferation, as well as the influence of other organ systems such
      as the bone marrow and central nervous system on the gastrointestinal tract.
      SUMMARY: These new published findings contribute to our overall understanding of
      gastroduodenal defense and suggest innovative avenues of future research and
      possible novel therapeutic targets.

PMID- 24100726
TI  - Helicobacter pylori infection: selected aspects in clinical management.
AB  - PURPOSE OF REVIEW: This review focuses on new aspects of recently published
      guidelines for the management of Helicobacter pylori infection as well as
      progress in diagnostic tests and treatment regimens. We also discuss new
      strategies for gastric cancer prevention. RECENT FINDINGS: The general
      recommendation to treat H. pylori infection whenever diagnosed still faces
      resistance for reasons that are pertinent to the diversity of related clinical
      outcomes and to the complexity of eradication regimens. Thus, new updated
      guidelines for the management of H. pylori infection have been released in
      several continents. Progress has been made in molecular diagnostic tests for the
      detection of antibiotic resistance and serological tests for the detection of
      advanced gastric atrophic changes. Effective quadruple therapies in various
      combinations of 'traditional drugs' have been introduced with sequential or
      concomitant order of administration. Moreover, traditional drugs in a new galenic
      formulation have been introduced to overcome increasing H. pylori antibiotic
      resistance. Effective strategies for gastric cancer prevention have been adopted
      in some countries with high gastric cancer incidence, and have successfully
      contributed to lower the gastric cancer incidence. A screen-and-treat strategy
      for individuals at increased risk for gastric cancer needs to be further explored
      also in areas with low/moderate incidence of gastric cancer. SUMMARY: New
      guidelines share many universal similarities across countries but respect and
      emphasize specific needs and requirements in individual communities. Various
      combinations of traditional drugs have been successfully introduced to overcome
      the increasing H. pylori antibiotic resistance. Gastric cancer prevention by a
      screen and treat strategy showed promising results.

PMID- 24100727
TI  - Dyspepsia.
AB  - PURPOSE OF REVIEW: Dyspepsia affects up to 40% of the general population and
      significantly reduces quality of life. A small proportion of patients have peptic
      ulcer disease as cause and this can be treated empirically with Helicobacter
      pylori eradication therapy in those that are infected. Approximately 20% have
      gastro-oesophageal reflux disease and this can be effectively treated with proton
      pump inhibitor therapy. Patients who remain symptomatic may warrant an endoscopy,
      but most will have functional dyspepsia. Treatment of functional dyspepsia
      remains a challenge. RECENT FINDINGS: Recent large randomized trials suggest
      tricyclic antidepressant therapy may be effective in functional dyspepsia. A
      phase III randomized controlled trial reports that a new prokinetic, acotiamide,
      reduces dyspepsia symptoms in functional dyspepsia patients. There are also
      preliminary data that suggest buspirone, a drug that promotes gastric
      accommodation, is also effective in functional dyspepsia. There are also data to
      suggest that functional dyspepsia is caused by subtle manifestations of
      inflammation in the upper gastrointestinal tract, possibly caused by food
      sensitivity or a change in gut flora. SUMMARY: The initial management of
      dyspepsia is well established, but managing those with continued symptoms is a
      challenge. Antidepressants and newer gastric motility agents show promise.
      Targeting the diet and gut microbiome is another area for future research in
      functional dyspepsia.

PMID- 24100729
TI  - Gastric secretion.
AB  - PURPOSE OF REVIEW: The review summarizes the past year's literature, basic
      science and clinical, regarding the neural, paracrine, hormonal, and
      intracellular regulation of gastric acid secretion. RECENT FINDINGS: Gastric acid
      facilitates the digestion of protein as well as the absorption of iron, calcium,
      vitamin B(12), and certain medications (e.g. thyroxin). It also kills ingested
      microorganisms and prevents bacterial overgrowth, enteric infection, and possibly
      spontaneous bacterial peritonitis. Stimulants of acid secretion include
      histamine, gastrin, acetylcholine, and ghrelin. Inhibitors include somatostatin,
      nefstatin-1, interleukin-11, and calcitonin gene-related peptide. Helicobacter
      pylori stimulates or inhibits acid secretion depending upon the time course of
      infection and the area of the stomach predominantly infected. Acute infection
      activates calcitonin gene-related peptide sensory neurons coupled to inhibition
      of histamine and acid secretion. Serum chromogranin A, a marker for
      neuroendocrine tumors, is elevated in patients taking proton pump inhibitors.
      SUMMARY: Progress continues in our understanding of the regulation of gastric
      acid secretion in health and disease, as well as the function of gastric
      neuroendocrine cells. The recognition that gastrin is not only a secretagogue but
      also a trophic hormone has led to new research into the role of gastrin and its
      receptor (cholecystokinin-2 receptor) in carcinogenesis and the development of
      cholecystokinin-2 receptor antagonists.

PMID- 24100730
TI  - Stomach and duodenum.

PMID- 24100728
TI  - Zollinger-Ellison syndrome: recent advances and controversies.
AB  - PURPOSE OF REVIEW: To review the recent advances and current controversies in
      patients with Zollinger-Ellison syndrome (ZES). RECENT FINDINGS: Recent advances
      in the management of ZES include: improved understanding of the pathogenesis of
      gastrinoma and pancreatic neuroendocrine tumors, new prognostic classification
      systems, new diagnostic algorithms, more sensitive localization studies, new
      treatment strategies including improved control of gastric acid secretion and
      role for surgery, and new approaches to patients with advanced disease.
      Controversies include: the best approach to a patient with hypergastrinemia
      suspected of possibly having ZES, the appropriate gastrin assay to use, the role
      of surgery in patients with ZES, especially those with multiple endocrine
      neoplasia type 1, and the precise order of therapeutic modalities in the
      treatment of patients with advanced disease. SUMMARY: This review updates
      clinicians regarding important advances and controversies required to optimally
      diagnose and manage patients with ZES.

PMID- 24100731
TI  - Lentivirus-mediated shRNA targeting of cyclin D1 enhances the chemosensitivity of
      human gastric cancer to 5-fluorouracil.
AB  - Gastric cancer is one of the major public health problems. Despite new
      chemotherapeutic treatments, the prognosis of gastric cancer remains poor. 5
      Fluorouracil (5-FU) is used as a standard chemotherapy drug in gastric cancer.
      However, 5-FU resistance develops frequently and is a main cause of chemotherapy
      failure in human gastric cancer. Overexpression of cyclin D1 is related to rapid
      cell growth, a poor prognosis and increased chemoresistance in several types of
      cancers. In this study, we investigated whether treatment of gastric cancer cells
      with shRNA targeting cyclin D1 (ShCCND1) or 5-FU, alone or in combination,
      influences the activation of phosphorylated AKT (pAKT) and pNFkappaB, which are
      markers that are increased in 5-FU chemoresistance. We also investigated the
      effect of combined treatment with ShCCND1 and 5-FU on cell growth and
      chemosensitivity to 5-FU in the gastric cancer cell line AGS. The data showed
      that ShCCND1-mediated cyclin D1 downregulation in AGS cells significantly
      inhibited cell proliferation, cell mobility and clonogenicity. In addition,
      combined treatment with ShCCND1 and 5-FU significantly decreased the survival
      rate of AGS cells, compared to single-treatment with either agent. These results
      demonstrated that ShCCND1 increases 5-FU chemosensitivity, a conclusion that is
      also supported by the concomitant reduction in expression of pAKT and pNFkappaB,
      increase of G1 arrest and induction of apoptosis. Taken together, these data
      provide further evidence that therapeutic strategies targeting cyclin D1 may have
      the dual advantage of suppressing the growth of cancer cells, while enhancing
      their chemosensitivity.

PMID- 24100733
TI  - The cytotoxic effect of alpha-tomatine in MCF-7 human adenocarcinoma breast
      cancer cells depends on its interaction with cholesterol in incubation media and
      does not involve apoptosis induction.
AB  - In recent years, alpha-tomatine has been studied for its anticancer activity. In
      the present study, we focused on the cytotoxic effect of alpha-tomatine in the
      MCF-7 human breast adenocarcinoma cell line, its mechanism of action,
      biotransformation and stability in the culture medium. We observed an inhibition
      of cell proliferation and viability at concentrations of 6 and 9 uM but then a
      recovery of cells occurred. The recovery was not caused by the biotransformation
      of alpha-tomatine in MCF-7 cells, but by a substantial decrease in the
      concentration of alpha-tomatine in the culture medium due to its binding with
      cholesterol. Regarding the mechanism of action of alpha-tomatine, we observed no
      DNA damage, no changes in the levels of the proteins p53 and p21(WAF1/Cip1), and
      no apoptosis (neither activated caspase-8 and -9, nor sub-G1 peak, or
      morphological signs). We found a loss of ATP in alpha-tomatine-treated cells.
      These results support the conclusion that alpha-tomatine does not induce
      apoptosis in the MCF-7 cell line.

PMID- 24100734
TI  - Acute kidney injury in patients with the influenza A virus (H1N1).

PMID- 24100735
TI  - Physical therapy during hemodialyse in patients with chronic kidney disease.
AB  - INTRODUCTION: The aim of this study was to evaluate the effects of a physical
      therapy program in patients with chronic kidney disease (CKD) during hemodialysis
      (HD). METHODS: Fifty-six CKD patients participated for 16 months in a supervised
      physical therapy program in HD sessions. They underwent evaluation before the
      start of the program and 16 months after this training. The program consisted of
      muscle strengthening exercises, stretching and stationary exercise bike. The
      analysis is composed of test six-minute walk (6MWT), level of effort by the BORG
      scale test of one repetition maximum (1RM) to measure the quadriceps strength,
      quality of life (QOL) and arterial blood pressure (BP), heart (HR) and
      respiratory (RR). RESULTS: The results showed an increase in distance traveled
      for the 6MWT and quadriceps strength, reduction of HR and RR and improvement in
      total score SF-36, but significantly in functional capacity and pain BP reduced,
      though not significantly. It was found by the Spearman correlation test, only in
      the areas correralation pain and functional capacity, individually, with the
      increase in distance walked in 6MWT; correlation between decreases in HR and RR
      linked to reduction in the Borg scale. CONCLUSION: Physical therapy, through an
      exercise program during the intradialytic period, can provided a significant
      improvement of QOL and physical ability of patients with CKD.

PMID- 24100736
TI  - Adductor pollicis muscle thickness as a predictor of handgrip strength in
      hemodialysis patients.
AB  - INTRODUCTION: Recently, the adductor pollicis muscle thickness (APMT) has been
      suggested as a new nutritional marker in several population. OBJECTIVE: In view
      of the scarce data regarding the use of this marker in CKD patients, we aimed to
      evaluate APMT and its association with nutritional parameters in patients on
      hemodialysis. METHODS: We evaluated 73 hemodialysis patients (52.3 +/- 17 years,
      without residual renal function). The APMT was assessed in the non vascular
      access arm by means of skinfold caliper. Body composition (bioelectrical
      impedance), handgrip strength (HGS, dynamometer), nutritional status (subjective
      global assessment), and laboratory parameters (creatinine, total protein and
      albumin) were also evaluated. RESULTS: Subjects with APMT values above the median
      were in greater proportion black/ brown, younger and had higher HGS. The APMT
      correlated positively with HGS, albumin and body cell mass (%), and negatively
      with age. In the linear regression analysis adjusted for sex, age and length on
      hemodialysis, APMT was independently associated with HGS. CONCLUSION: APMT was
      able to predict HGS in hemodialysis patients, suggesting APMT as a promising
      nutritional marker in this population.

PMID- 24100737
TI  - Acute kidney injury in patients infected by H1N1: clinical histological
      correlation in a series of cases.
AB  - INTRODUCTION: Influenza A (H1N1) virus was first reported on April 2009 and,
      since then, several studies have reported the characteristics concerning the
      clinical presentation and pulmonary involvement. However, accurate information
      about the acute kidney injury (AKI) and kidney histopathological findings in
      these patients remain scarce. OBJECTIVE: To describe the kidney histopathological
      findings of 6 patients with H1N1 who developed AKI and underwent kidney biopsy,
      correlating them with clinical features. METHODS: We studied six patients
      admitted to Hospital de Clinicas UFPR with a PCR-confirmed diagnosis of H1N1who
      developed ARF and underwent kidney biopsy. We reviewed their medical file and the
      microscopy findings of the biopsy. RESULTS: Clinical and/or laboratory evidence
      of AKI was present in all cases, and only one did not present oliguria. Kidney
      tissues revealed glomerular lesions in two patients: one patient, with systemic
      lupus erythematosus, showed changes consistent with lupus nephritis class III A-C
      according to the ISN/RPS 2003 and focal thrombotic microangiopathy; the other one
      had intercapillary nodular glomerulosclerosis, but without clinical or laboratory
      evidence of diabetes. Vacuolar degenerative tubular changes were present in all
      cases, with focus of oxalosis in two cases. Mild to moderate atherosclerosis was
      found in two patients. CONCLUSION: In this study, varying degrees of vacuolar
      degenerative tubular changes were present in all patients, but there were no
      signs of acute tubular necrosis. It seems that in the present study a prerenal
      cause of acute renal failure was the main involved mechanim to explain the cause
      of renal failure in these patients.

PMID- 24100738
TI  - Steroid-resistant idiopathic nephrotic syndrome in children: long-term follow-up
      and risk factors for end-stage renal disease.
AB  - INTRODUTION: Steroid resistant idiopathic nephrotic syndrome (SRINS) in children
      is one of the leading causes of progression to chronic kidney disease stage V
      (CKD V)/end stage renal disease (ESRD). OBJECTIVE: The aim of this retrospective
      study is to evaluate the efficacy of immunosuppressive drugs (IS) and to identify
      risk factors for progression to ESRD in this population. METHODS: Clinical and
      biochemical variables at presentation, early or late steroid resistance,
      histological pattern and response to cyclosporine A (CsA) and cyclophosfamide
      (CP) were reviewed in 136 children with SRINS. The analyzed outcome was the
      progression to ESRD. Univariate as well as multivariate Cox-regression analysis
      were performed. RESULTS: Median age at onset was 5.54 years (0.67-17.22) and
      median follow up time was 6.1 years (0.25-30.83). Early steroid-resistance was
      observed in 114 patients and late resistance in 22. Resistance to CP and CsA was
      62.9% and 35% respectively. At last follow-up 57 patients reached ESRD. The renal
      survival rate was 71.5%, 58.4%, 55.3%, 35.6% and 28.5% at 5, 10, 15, 20 and 25
      years respectively. Univariate analysis demonstrated that older age at onset,
      early steroid-resistance, hematuria, hypertension, focal segmental
      glomerulosclerosis (FSGS), and resistance to IS were risk factors for ESRD. The
      Cox proportional-hazards regression identified CsAresistance and FSGS as the only
      predictors for ESRD. CONCLUSION: Our findings showed that CsA-resistance and FSGS
      were risk factors for ESRD.

PMID- 24100739
TI  - Immunosupressive therapy in children with steroid-resistant nephrotic syndrome:
      single center experience.
AB  - INTRODUCTION: [corrected] Nephrotic syndrome is one of the most frequent
      glomerular diseases among children, and steroid therapy remains as the treatment
      choice. In spite of this, 10 to 15% of the patients are steroidresistant, and the
      best therapy for such cases has never been defined. Mycophenolate acid (MA) is
      one of the treatments used in such situations. OBJECTIVE: To describe the
      clinical behavior of children diagnosed with steroid-resistant nephrotic syndrome
      (SRNS) and to assess the therapeutic response to MA. METHODS: This was a
      retrospective and descriptive study. RESULTS: 26 clinical records of patients
      with SRNS; 70% male and 30% female. All patients underwent kidney biopsies, which
      showed a predominance of focal segmental glomerulosclerosis (FSGS). The
      immunosuppresive drugs used were: Mycophenolate mofetil (MMF) 100%, Cyclosporine
      69.2%, Cyclophosphamide 23.1%, and Rituximab 23%. One month after treatment
      initiation with MMF 61.5% achieved remission. The median of relapses per year for
      the patients was 3 (p25: 2.75 - p75: 4). This median became 1 (p25: 1 - p75:
      3.25) after using this medication (p = 0.08). Furthermore, prior to the start of
      the MMF treatment, the median of the steroid dose was 1 (p25: 0.5- p75: 1.62)
      mg/k/day. After using MMF, this median became 0.07 (p25: 0 - p75: 0.55) mg/k/day
      (p < 0.001), in 8 patients prednisolone was stopped. CONCLUSION: In our
      experience, treatment with MMF showed positive results such as decrease in the
      frequency of relapses, less proteinuria, and reduction in the dose of steroids
      administered without deterioration of glomerular filtration rates. However, more
      studies are needed to assess efficacy, safety, and optimal dosage.

PMID- 24100740
TI  - Tuberculosis prevalence in renal transplant recipients: systematic review and
      meta-analysis.
AB  - INTRODUCTION: Tuberculosis (TB) prevalence in subjects with kidney
      transplantation (KTX) is greater than in general population. We aimed to realize
      a systematic review and meta-analysis of prevalence of TB in KTX (TB-KTX).
      METHODS: We searched by the texts in electronic databases and references were
      reviewed. We estimated the pooled prevalence of TB-KTX subjects and we also
      conducted analysis by meta-regression. TB prevalence in general population
      (0.18%; 95% IC = 0.16-0.20) was reference to comparison. RESULTS: We screened 253
      papers, which 41 studies entered in analysis. The pooled prevalence of TB-KTX was
      2.51% (95% CI = 2.17-2.85). In the meta-regression sample size > 2.501 subjects
      and high prevalence of TB in general population remained associated with TB-KTX.
      CONCLUSION: TB prevalence in KTX was 14 times greater than in general population.
      Thus, we highlighted the necessity that planning of measures for prevention and
      control of TB for this population should be agenda in discussions of health
      sector.

PMID- 24100741
TI  - Peritonitis in patients on peritoneal dialysis: analysis of a single Brazilian
      center based on the International Society for Peritoneal Dialysis.
AB  - INTRODUCTION: Peritonitis remains the major complication in patients on
      peritoneal dialysis (PD), peritonitis rates vary in the literature, reflecting
      differences between countries, study design and populations. OBJECTIVE: This
      study aimed to determine the rates of peritonitis episodes per year at risk
      (ep./yr), ep./yr by causative microorganism and median of peritonitis in patients
      on peritoneal dialysis at Hospital Sao Lucas. METHODS: Retrospective descriptive
      study, with a study sample composed of patients treated with peritoneal dialysis
      at the Renal Unit of Sao Lucas Hospital between the periods from 1984 to August
      2012. Only patients with complete data were considered. RESULTS: Of the 427
      patients analyzed, 53.2% (227) were females, mean age was 48.0 +/- 19.9 years,
      13% (56) were diabetics and 71.5% (303) of the patients performed their own
      treatment. There were 503 episodes of peritonitis and 255 patients had at least
      one episode. Coagulase-negative Staphylococcus was the most prevalent organism.
      The main causes of dropout from treatment were death, renal transplantation and
      peritonitis with 34.4, 25.8 and 19.2%, respectively. The rate of peritonitis was
      0.63 ep./yr, rates by microorganism were 0.18 ep./yr for coagulase-negative
      Staphylococcus, 0.12 ep./yr for Staphylococcus aureus and Gram negative. The
      median of peritonitis in the unit was 0.41 ep./yr. CONCLUSION: The rate of
      peritonitis ep./yr and median of patients studied is within the recommended
      minimum, but below the suggested targets proposed by the position statement of
      ISPD.

PMID- 24100742
TI  - Integrative review: indicators of result process of organ donation and
      transplants.
AB  - OBJECTIVE: Identify by integrated review the main result indicators in the
      process of organ donation and transplants used in Brazil and worldwide. The
      integrated review of this literature was performed on bibliographic database
      MedLine/PubMed and LILACS and governmental and nongovernmental sites between 1995
      and 2011. The describers/keywords used were organ donations, organ transplant and
      results in health, being selected 26 articles and nine sites. The evidence level
      classification in the articles changed from one to six. RESULTS: The evidence
      level in the articles in its totality was 66.6% was four (12:18 PubMed) all the
      articles of LILACS database (8). The indicators showed in the articles intends to
      evaluate, assess, measure and control data related to the profile of the donor,
      clinical and hospital conditions, ischemia timing, organ size, surgical procedure
      and the complications that came from transplants.

PMID- 24100743
TI  - Biomarkers of acute kidney injury.
AB  - Creatinine remains the standard for laboratory diagnosis of AKI. Efforts to
      prevent nephrotoxicity have been harmed by the delay in the diagnosis of AKI
      criteria by using only the creatinine as a marker, therefore there is great
      interest in identifying early reliable biomarkers. Moreover, early treatment of
      ARF can be correlated with a better prognosis and identification of biomarkers
      for early diagnosis would improve the efficacy of a therapeutic strategy. Thus,
      it becomes imperative to find biomarkers that can stratify correctly the extent
      of renal damage that each patient has suffered and the risk of developing chronic
      kidney disease (CKD). Here, we review the main features of emerging biomarkers in
      nephrology. 

PMID- 24100744
TI  - [Eculizumab for the treatment of atypical hemolytic uremic syndrome: case report
      and revision of the literature].
AB  - SHU atypical (aHUS), that is, not associated with Escherichia coli Shiga
      toxinproducing, is seen in 5 to 10% of cases of Hemolytic Uremic Syndrome (HUS),
      and can occur at any age and may be sporadic or familial. The prognosis in these
      cases is reserved, with high mortality and morbidity in the acute phase of the
      disease, and about 50% of cases can develop chronic kidney disease. The increased
      knowledge of the pathogenesis of aHUS (overactivation of the alternative pathway
      of complement), was accompanied by the appearance of a drug, eculizumab, which
      acts as an inhibitor of membrane attack complex. Our goal is to report a case of
      infant with aHUS with excellent clinical and laboratory response with the use of
      eculizumab. 14 month old infant, previously healthy, male, presented anemia and
      thrombocytopenia at 12 months of age. He was treated with corticosteroids and
      forwarded to our service for high blood pressure. However, the scans showed
      nephrotic proteinuria with renal involvement and hypoalbuminemia with direct
      Coombs negative. He developed anemia, thrombocytopenia, worsening of renal
      function and hypertension. Renal biopsy showed thrombotic microangiopathy (TMA).
      On the non-hemolytic anemia, thrombocytopenia and acute renal failure with
      histological substrate MAT, was diagnosed of aHUS. The patient received
      eculizumab excellent clinical and laboratory response. This case shows the
      importance of early diagnosis and treatment of the aHUS. Eculizumab is effective
      and keeps long-term remission, avoiding invasive measures such as plasmapheresis,
      which resolves only part of the picture. 

PMID- 24100745
TI  - Pain determinants of pain in autosomal dominant polycystic kidney disease.
AB  - Pain is the most common symptom reported by ADPKD patients, afflicting
      approximately 60% of cases and may result from renal hemorrhage, calculi, urinary
      tract infections, cyst rupture, or due to stretching of the capsule or traction
      of the renal pedicle. We have recently investigated pain patterns in AD-PKD
      patients using a translated version of a pain questionnaire specific for AD-PKD
      population. The questionnaire revealed that 67% patients with ADPKD exhibited
      some type of pain. The findings of that study emphasized that pain appeared early
      in the course of ADPKD, when patients still exhibited preserved renal function.
      In the present study, a multivariate logistic regression analysis disclosed that
      renal volume (9-fold increased risk) and nephrolithiasis (4-fold increased risk)
      were the most important determinant factors for pain in ADPKD patients with
      preserved renal function, after adjustments for the presence of hypertension and
      duration of the disease. 

PMID- 24100747
TI  - Penta- and heteropentadienyl ligands coordinated to beryllium.
AB  - In this work we have performed a systematic study of new organometallic complexes
      containing penta- and heteropentadienyl (CH2CHCHCHX, X = CH2, O, NH, S) ligands
      coordinated to beryllium. Calculated complexes were studied using the density
      functional theory (PBE) in combination with the 6-311++G(3d,2p) basis set. The
      coordination number on the beryllium atom varies according to the type of ligand.
      Pentadienyl ligand shows hapticities eta(1) and eta(5), while heteropentadienyl
      ligands display eta(1) and eta(2) hapticities. A Wiberg bond indices study was
      performed in order to get information about their bond orders. 

PMID- 24100748
TI  - Hepatitis C virus genotype 5: prospective evaluation of peginterferon/ribavirin
      treatment efficacy and predictive value of on-treatment virological responses for
      sustained virological response.
AB  - GOALS: To examine the treatment efficacy of a combination of pegylated interferon
      alpha (PegIFNa) plus ribavirin in patients chronically infected with hepatitis C
      virus genotype 5 (HCV-5) and to assess the on-treatment virological responses as
      predictors of sustained virological response (SVR). BACKGROUND: HCV-5 is
      uncommonly reported, and little therapeutic data is available regarding previous
      retrospective studies yielding contradictory results. STUDY: In a prospective,
      open-label, single-center study, 27 treatment-naive HCV-5 patients, treated for
      48 weeks with PegIFNa-2a/ribavirin, were evaluated. Rapid viral response (RVR),
      early viral response (EVR), 24-week viral response (24-wVR), end-of-treatment
      response (ETR), and SVR were assessed, defined as negative viral load at weeks 4,
      12, 24, 48, and 72 after treatment initiation, respectively. RESULTS: Attainment
      of SVR was observed in 17 of the 27 (63%) patients. RVR, EVR, and 24-wVR occurred
      in 16 (59.3%), 25 (92.6%), and 24 (88.9%) patients, respectively. All but 1
      patient achieving 24-wVR went on to achieve ETR (rate: 85.2%), but 6 patients
      subsequently relapsed (relapse rate: 26.1%). The positive/negative predictive
      values on SVR were: 93.8%/81.8% for RVR, 68%/100% for EVR, and 66.7%/66.7% for 24
      wVR. CONCLUSIONS: Patients with HCV-5 showed an overall good response to a 48
      week combined antiviral treatment (SVR: 63%). Albeit the ETR was high (85.2%),
      attainment of SVR remained affected by a substantial relapse rate, in our setting
      26.1%. The predictive value of early viral dynamics on SVR merits adequate
      consideration in larger clinical trials targeting to optimize treatment for
      patients infected with HCV-5.

PMID- 24100749
TI  - A systematic review of sorafenib in Child-Pugh A patients with unresectable
      hepatocellular carcinoma.
AB  - BACKGROUND AND GOALS: Several studies have demonstrated that sorafenib is
      effective in the treatment of unresectable hepatocellular carcinoma (HCC). We
      performed a systematic review of the efficacy and safety of sorafenib in Child
      Pugh A patients with unresectable HCC. The value of sorafenib treatment in
      different subgroups was examined. MATERIALS AND METHODS: A search of the
      literature published up to July 2012 was conducted. Pubmed, Embase, and the
      Cochrane library were searched and only randomized controlled trials were
      included. RESULTS: Five randomized controlled trials consisting of 1462 patients
      with unresectable HCC were included. Meta-analyses demonstrated that sorafenib
      improved the control rate of the disease [relative risk, 1.85; 95% confidence
      interval (CI), 1.55, 2.20; P<0.001], decreased the risk for tumor progression
      (hazard ratios, 0.61; 95% CI, 0.51, 0.73; P<0.001), and decreased mortality
      (hazard ratios, 0.71; 95% CI, 0.56, 0.89; P<0.001), relative to placebo. Subgroup
      analyses indicated that sorafenib-based treatments were effective in unresectable
      HCC regardless of the etiology, performance status, Barcelona Clinic Liver Cancer
      stage, alanine transaminase/asparate transaminase, bilirubin, and alpha-feto
      protein level, except in the subgroup of prior local therapy. Sorafenib was
      associated with a higher risk of adverse effects than placebo. The risk for grade
      3-4 hand-foot skin reactions, rash or desquamation, diarrhea, and hypertension
      was much higher in the sorafenib treatment group. These side effects could often
      be mitigated with appropriate treatment. CONCLUSIONS: Sorafenib was a moderately
      effective and safe oral drug for use in Child-Pugh A patients with unresectable
      HCC. Sorafenib monotherapy is not recommended for treating intermediate-stage
      HCC. More research is needed on the efficacy of sorafenib treatment in patients
      with prior local therapy.

PMID- 24100750
TI  - Plasma intestinal fatty acid-binding protein levels correlate with morphologic
      epithelial intestinal damage in a human translational ischemia-reperfusion model.
AB  - BACKGROUND AND AIM: Intestinal fatty acid-binding protein (I-FABP) is a useful
      marker in the detection of intestinal ischemia. However, more insight into the
      test characteristics of I-FABP release is needed. This study aimed to investigate
      the relationship between plasma I-FABP levels and the severity of ischemic
      mucosal injury, and define the clinical usefulness of systemic I-FABP following
      ischemia. METHODS: In a human experimental model, 6 cm of the jejunum, to be
      removed for surgical reasons, was selectively exposed to either 15, 30, or 60
      minutes of ischemia (I) followed by 30 and 120 minutes of reperfusion (R). Blood
      and tissue was sampled at all time points. Arteriovenous (V-A) concentration
      differences of I-FABP were measured. Tissue sections were stained with
      hematoxylin/eosin, and villus height was measured to score epithelial damage.
      RESULTS: Histologic analysis showed only minor reversible intestinal damage
      following 15 I and 30 I; however, severe irreversible epithelial damage was
      observed in the jejunum exposed to 60 I. I-FABP V-A differences paralleled the
      degree of tissue damage over time [7.79 (+/- 1.8) ng/mL, 128.6 (+/- 44.2) ng/mL,
      463.3 (+/- 139.8) ng/mL for 15 I, 30 I and 60 I, respectively]. A good
      correlation was found between histologic epithelial damage and V-A I-FABP (r=
      0.82, P<0.001). Interestingly, systemic I-FABP levels were significantly
      increased after 60 I of this short small intestinal segment. CONCLUSIONS: This
      study demonstrates the relationship between the duration of ischemia and the
      extent of tissue damage, which is reflected by I-FABP V-A plasma levels. In
      addition, systemic I-FABP levels appear valuable in detecting irreversible
      intestinal ischemia-reperfusion damage.

PMID- 24100751
TI  - Comparison of procedural sequence in same-day consecutive bidirectional endoscopy
      using moderate sedation: a prospective randomized study.
AB  - BACKGROUND: A sequential bidirectional endoscopy is commonly performed. However,
      the optimal sequence of procedures for same-day bidirectional endoscopy using
      moderate sedation has not been established. GOALS: The aim of this study was to
      characterize the optimal sequence of endoscopies for sequential bidirectional
      endoscopy. STUDY: This was a single-center, prospective, randomized study. A
      total of 163 patients aged 18 to 80 years, who were referred for bidirectional
      endoscopy for any indication, were randomized to start with upper or lower
      endoscopy. Initially, all patients received intravenously 50 mg of meperidine and
      2.5 mg of midazolam. Patient's discomfort and satisfaction, as expressed by the
      amount of analgesia added to sustain conscious sedation, and the postprocedure
      satisfaction reported by the patients were set as primary outcomes. RESULTS:
      There was no significant difference in the total dose of midazolam added,
      patient's pain assessment and satisfaction from the anesthesia and the procedure,
      duration of endoscopies, or the time to cecal intubation between the
      esophagogastroduodenoscopy first and colonoscopy first groups. The rate of
      diagnosis of significant pathologies and the rate of procedures performed during
      the examinations were similar in both the study groups. Evaluation of patient's
      postprocedural recovery did not reveal significant differences. There was no
      significant variance between the performing physicians regarding anesthetic
      dosing, duration of examination, pain scoring, and the related patient's pain
      postprocedural assessment. CONCLUSIONS: There were no significant differences in
      the patient's discomfort and satisfaction, regardless of the procedural sequence.

PMID- 24100752
TI  - Co-management between hospitalist and hepatologist improves the quality of care
      of inpatients with chronic liver disease.
AB  - BACKGROUND AND GOALS: Our institution shifted the care of patients with chronic
      liver disease (CLD) from Internal Medicine faculty, house staff, and consulting
      hepatology service to a co-managed unit staffed by academic hospitalists and
      hepatologists. The effect of co-management between hospitalists and hepatologists
      on the care of patients hospitalized with complications of CLD such as
      spontaneous bacterial peritonitis (SBP) is unknown. STUDY: A retrospective chart
      review of 56 adult patients admitted with CLD and SBP from July 1, 2004 to June
      30, 2010 was performed. Adherence rates to current management guidelines were
      measured along with costs and outcomes of care. RESULTS: Patients admitted under
      the 2 models of care were similar; however, they consistently underwent
      paracentesis within 24 hours (100% vs. 79%, P=0.013), had appropriate avoidance
      of fresh-frozen plasma use (75% vs. 43%, P=0.05), received albumin (97% vs. 65%,
      P=0.002), and were discharged on SBP prophylaxis (91% vs. 37%, P<0.001) under the
      co-managed model compared with the conventional model. Costs of care were similar
      between the 2 groups. We note a trend toward improved outcomes of care under the
      co-management model as measured by transfer rates to the intensive care unit,
      inpatient mortality, 30-day readmission, and mortality rates. CONCLUSIONS: These
      results support co-management between hospitalists and hepatologists as a
      superior model of care for hospitalized patients with SBP. Furthermore, this
      study adds to the growing literature indicating that efforts are needed to
      improve the quality of care delivered to CLD patients.

PMID- 24100753
TI  - Novel disposable transnasal endoscopy for assessment of esophageal motor
      function.
AB  - BACKGROUND: A novel disposable transnasal endoscopy (DTE) with a portable system
      has been developed to provide unsedated esophagoscopy by modifying capsule
      endoscopy. The aim of this study was to assess the feasibility of DTE to evaluate
      esophageal motor function. MATERIALS AND METHODS: Patients with or suspected
      esophageal motility disorders and healthy volunteers were enrolled. Participants
      underwent esophageal high-resolution manometry and DTE in random order on
      different days. Motility was observed with DTE at 1, 8, and 16 cm above the
      gastroesophageal junction. RESULTS: Twenty healthy volunteers and 20 symptomatic
      subjects participated (8 achalasia, 5 scleroderma, 3 diffuse esophageal spasm, 1
      hypertensive peristalsis, 1 peristaltic dysfunction, and 22 normal esophageal
      function). The normal findings on DTE were as follows. As the subject swallowed
      water, swallow-induced relaxation with elevation of the lower esophageal
      sphincter caused the endoscope to cross the Z-line into the gastric lumen. After
      the passage of water and air, complete closure of the lower esophageal sphincter
      occurred, with the return of the endoscope to its previous position. During the
      resting stage of the esophageal body, an air bubble could be seen in the center
      of the radially wrinkled and occluded lumen. The endoscopic diagnosis was in
      agreement with the clinical diagnosis in all but 2. Most of the participants
      reported acceptable discomfort during DTE and 62.5% of the subjects preferred DTE
      to manometry. CONCLUSIONS: DTE can accurately characterize normal esophageal
      motor function, allowing the diagnosis of esophageal motility disorders. DTE has
      potential widespread applications, especially in outpatient clinics.

PMID- 24100754
TI  - Peppermint oil for the treatment of irritable bowel syndrome: a systematic review
      and meta-analysis.
AB  - GOALS: The aim of this study was to assess the efficacy and safety of enteric
      coated peppermint oil capsules compared with placebo for the treatment of active
      irritable bowel syndrome (IBS). BACKGROUND: IBS is a common disorder that is
      often encountered in clinical practice. Medical interventions are limited and the
      focus is on symptom control. STUDY: Randomized placebo-controlled trials with a
      minimum treatment duration of 2 weeks were considered for inclusion. Cross-over
      studies that provided outcome data before the first cross-over were included. A
      literature search upto February 2013 identified all applicable randomized
      controlled trials. Study quality was evaluated using the Cochrane risk of bias
      tool. Outcomes included global improvement of IBS symptoms, improvement in
      abdominal pain, and adverse events. Outcomes were analyzed using an intention-to
      treat approach. RESULTS: Nine studies that evaluated 726 patients were
      identified. The risk of bias was low for most of the factors assessed. Peppermint
      oil was found to be significantly superior to placebo for global improvement of
      IBS symptoms (5 studies, 392 patients, relative risk 2.23; 95% confidence
      interval, 1.78-2.81) and improvement in abdominal pain (5 studies, 357 patients,
      relative risk 2.14; 95% confidence interval, 1.64-2.79). Although peppermint oil
      patients were significantly more likely to experience an adverse event, such
      events were mild and transient in nature. The most commonly reported adverse
      event was heartburn. CONCLUSIONS: Peppermint oil is a safe and effective short
      term treatment for IBS. Future studies should assess the long-term efficacy and
      safety of peppermint oil and its efficacy relative to other IBS treatments
      including antidepressants and antispasmodic drugs.

PMID- 24100755
TI  - Vascular invasion in hepatocellular carcinoma: prevalence, determinants and
      prognostic impact.
AB  - GOALS/BACKGROUND: Macrovascular invasion (MaVI) is often detected by radiologic
      imaging in hepatocellular carcinoma (HCC) patients and may affect their long-term
      survival. We aimed to investigate the prevalence, determinants, and prognostic
      impact of MaVI in patients with HCC receiving curative and noncurative therapies.
      STUDY: A total of 2654 HCC patients in a single center were identified. The risk
      factors and prognostic determinants of MaVI were determined. RESULTS: A total of
      928 (35%) patients had MaVI. Old age, lower serum alpha-fetoprotein level, higher
      serum sodium level, good performance status, smaller total tumor volume, and
      better liver functional reserve were significantly associated with a lower risk
      for VI. In the Cox proportional hazards model, patients with lower serum albumin
      level, higher serum bilirubin and alpha-fetoprotein level, worse performance
      status, the presence of ascites, and MaVI independently predicted a decreased
      long-term survival in patients undergoing both curative and noncurative
      treatments. In addition, lower sodium level and larger tumor size were
      independently associated with a poor outcome in the noncurative treatment group.
      Of the patients with MaVI, the 1-year survival rates for patients receiving
      surgical treatment, local ablation, transarterial chemoembolization, and
      supportive care were 83%, 75%, 57%, and 24%, respectively (P<0.001). CONCLUSIONS:
      MaVI represents a distinct tumor phenotype of HCC and is associated with younger
      age, aggressive tumor behavior, poor liver functional reserve, and poor
      performance status. It adversely affects the survival of HCC patients independent
      of treatment strategy. Intensive anticancer therapy should be proposed to achieve
      a better long-term survival for the at-risk patients.

PMID- 24100756
TI  - Midodrine for paracentesis-induced circulatory dysfunction.

PMID- 24100757
TI  - Landscapes of fear or competition? Predation did not alter habitat choice by
      Arctic rodents.
AB  - In systems where predation plays a key role in the dynamics of prey populations,
      such as in Arctic rodents, it is reasonable to assume that differential patterns
      of habitat use by prey species represent adaptive responses to spatial variation
      in predation. However, habitat selection by collared (Dicrostonyx groenlandicus)
      and brown (Lemmus trimucronatus) lemmings depends on intra- and inter-specific
      densities, and there has been little agreement on the respective influences of
      food abundance, predators, and competition for habitat on lemming dynamics. Thus,
      we investigated whether predation affected selection of sedge-meadow versus
      upland tundra by collared lemmings in the central Canadian Arctic. We first
      controlled for the effects of competition on lemming habitat selection. We then
      searched for an additional signal of predation by comparing habitat selection
      patterns between 12 control plots and one large grid where lemmings were
      protected from predators by fencing in 1996 and 1997, but not during 5 subsequent
      years when we monitored habitat use in the grid as well as in the control plots.
      Dicrostonyx used upland preferentially over meadows and was more numerous in 1996
      and 2011 than in other sample years. Lemmus was also more abundant in 1996 than
      in subsequent years, but its abundance was too low in the exclosure to assess
      whether exclusion of predators influenced its habitat selection. Contrary to the
      effects of competition, predation had a negligible impact on the spatial dynamics
      of Dicrostonyx, at least during summer. These results suggest that any
      differences in predation risk between the two habitats have little direct
      influence on the temporal dynamics of Dicrostonyx even if induced through
      predator-prey cycles. 

PMID- 24100758
TI  - Major consequences of minor damage: impacts of small grazers on fast-growing
      kelps.
AB  - Damage by small herbivores can have disproportionately large effects on the
      fitness of individual plants if damage is concentrated on valuable tissues or on
      select individuals within a population. In marine systems, the impact of tissue
      loss on the growth rates of habitat-forming algae is poorly understood. We
      quantified the grazing damage by an isopod Amphoroidea typa on two species of
      large kelps, Lessonia spicata and Macrocystis pyrifera, in temperate Chile to
      test whether non-lethal grazing damage could reduce kelp growth rates and
      photosynthetic efficiency. For L. spicata, grazing damage was widespread in the
      field, unevenly distributed on several spatial scales (among individuals and
      among tissue types) and negatively correlated with blade growth rates. In field
      experiments, feeding by A. typa reduced the concentration of photosynthetic
      pigments and led to large reductions (~80%) in blade growth rates despite limited
      loss of kelp biomass (0.5% per day). For M. pyrifera, rates of damage in the
      field were lower and high densities of grazers were unable to reduce growth rates
      in field experiments. These results demonstrate that even low per capita grazing
      rates can result in large reductions in the growth of a kelp, due the spatial
      clustering of herbivores in the field and the selective removal of
      photosynthetically active tissues. The impacts of small herbivores on plant
      performance are thus not easily predicted from consumption rates or abundance in
      the field, and vary with plant species due to variation in their ability to
      compensate for damage.

PMID- 24100759
TI  - Distinct charge dynamics in battery electrodes revealed by in situ and operando
      soft X-ray spectroscopy.
AB  - Developing high-performance batteries relies on material breakthroughs. During
      the past few years, various in situ characterization tools have been developed
      and have become indispensible in studying and the eventual optimization of
      battery materials. However, soft X-ray spectroscopy, one of the most sensitive
      probes of electronic states, has been mainly limited to ex situ experiments for
      battery research. Here we achieve in situ and operando soft X-ray absorption
      spectroscopy of lithium-ion battery cathodes. Taking advantage of the elemental,
      chemical and surface sensitivities of soft X-rays, we discover distinct lithium
      ion and electron dynamics in Li(Co(1/3)Ni(1/3)Mn(1/3))O2 and LiFePO4 cathodes in
      polymer electrolytes. The contrast between the two systems and the relaxation
      effect in LiFePO4 is attributed to a phase transformation mechanism, and the
      mesoscale morphology and charge conductivity of the electrodes. These discoveries
      demonstrate feasibility and power of in situ soft X-ray spectroscopy for studying
      integrated and dynamic effects in batteries.

PMID- 24100760
TI  - Controlling thread formation during tipstreaming through an active feedback
      control loop.
AB  - Microscale tipstreaming is a hydrodynamic phenomenon capable of producing
      submicron sized droplets within a microfluidic device. The tipstreaming process
      results in the drawing of a thin thread from a highly curved interface and occurs
      as a result of interfacial surfactant concentration gradients that develop due to
      elongational flows generated within flow focusing geometries. However, in
      conventional microfluidic devices, the thread formation is periodically
      interrupted by the formation of larger primary droplets. This study presents an
      active feedback control loop capable of eliminating the production of primary
      droplets and producing a continuous thread, and therefore a continuous droplet
      stream. A proportional controller is used to successfully control the position of
      the interface and generate a continuous thread. A derivative component is
      incorporated in an attempt to increase controller stability, but this component
      is found to be ineffective. Analysis of the tip position as a function of time is
      performed to determine the optimal proportional gain constant and set point value
      for the proportional controller that minimize fluctuations in the produced
      droplet sizes. The generation of a continuous thread facilitates the use of
      tipstreaming in several applications, including nanoparticle synthesis, chemical
      detection, and enzyme activity studies. 

PMID- 24100761
TI  - Canonical Wnt signaling activates miR-34 expression during osteoblastic
      differentiation.
AB  - The canonical Wnt signaling pathway is crucial for the regulation of bone mass in
      humans and for the development of osteoblasts. MicroRNAs (miRs) represent a class
      of non-coding RNAs, ~22 nucleotides in length, that regulate gene expression by
      targeting mRNAs for cleavage or translational repression. Several previous
      studies have demonstrated the involvement of miRNAs in modulating gene expression
      in osteoblasts and regulating osteoblast differentiation. In the present study,
      microRNA profiling was conducted using Wnt3a-C2C12 cells; C2C12 cells were
      transfected with a Wnt3a expression plasmid to activate canonical Wnt signaling.
      miR-34b-5p and miR-34c were identified to be upregulated by the activation of
      canonical Wnt signaling in C2C12 cells. Expression of mature miR-34b/c increased
      from low levels at day 0 to maximum levels at day 28 of MC3T3-E1 cell
      differentiation. To analyze the effects of these miRNAs on osteoblast
      differentiation, an antisense inhibitor was transfected into MC3T3-E1 cells and
      osteoblast-related gene expression was investigated. Knockdown of miR34b/c
      enhanced osteocalcin mRNA expression; however, alkaline phosphatase mRNA
      expression and activity were decreased by miR34b/c inhibition. These results
      indicated that miR-34b/c regulates gene expression by targeting regulators of the
      osteogenic pathways and thereby contributes to osteoblast differentiation.

PMID- 24100762
TI  - Computer-aided segmentation system for breast MRI tumour using modified automatic
      seeded region growing (BMRI-MASRG).
AB  - In this paper, an automatic computer-aided detection system for breast magnetic
      resonance imaging (MRI) tumour segmentation will be presented. The study is
      focused on tumour segmentation using the modified automatic seeded region growing
      algorithm with a variation of the automated initial seed and threshold selection
      methodologies. Prior to that, some pre-processing methodologies are involved.
      Breast skin is detected and deleted using the integration of two algorithms,
      namely the level set active contour and morphological thinning. The system is
      applied and tested on 40 test images from the RIDER breast MRI dataset, the
      results are evaluated and presented in comparison to the ground truths of the
      dataset. The analysis of variance (ANOVA) test shows that there is a
      statistically significance in the performance compared to the previous
      segmentation approaches that have been tested on the same dataset where ANOVA p
      values for the evaluation measures' results are less than 0.05, such as: relative
      overlap (p = 0.0002), misclassification rate (p = 0.045), true negative fraction
      (p = 0.0001) and sum of true volume fraction (p = 0.0001). 

PMID- 24100763
TI  - Opening and reversible control of a wide energy gap in uniform monolayer
      graphene.
AB  - For graphene to be used in semiconductor applications, a 'wide energy gap' of at
      least 0.5 eV at the Dirac energy must be opened without the introduction of
      atomic defects. However, such a wide energy gap has not been realized in
      graphene, except in the cases of narrow, chemically terminated graphene
      nanostructures with inevitable edge defects. Here, we demonstrated that a wide
      energy gap of 0.74 eV, which is larger than that of germanium, could be opened in
      uniform monolayer graphene without the introduction of atomic defects into
      graphene. The wide energy gap was opened through the adsorption of self-assembled
      twisted sodium nanostrips. Furthermore, the energy gap was reversibly
      controllable through the alternate adsorption of sodium and oxygen. The opening
      of such a wide energy gap with minimal degradation of mobility could improve the
      applicability of graphene in semiconductor devices, which would result in a major
      advancement in graphene technology. 

PMID- 24100764
TI  - Use of short tandem repeat fingerprinting to validate sample origins in hepatitis
      C virus molecular epidemiology studies.
AB  - Sequence analysis is used to define the molecular epidemiology and evolution of
      the hepatitis C virus. Whilst most studies have shown that individual patients
      harbour viruses that are derived from a limited number of highly related strains,
      some recent reports have shown that some patients can be co-infected with very
      distinct variants whose frequency can fluctuate greatly. Whilst co-infection with
      highly divergent strains is possible, an alternative explanation is that such
      data represent contamination or sample mix-up. In this study, we have shown that
      DNA fingerprinting techniques can accurately assess sample provenance and
      differentiate between samples that are truly exhibiting mixed infection from
      those that harbour distinct virus populations due to sample mix-up. We have
      argued that this approach should be adopted routinely in virus sequence analyses
      to validate sample provenance. 

PMID- 24100765
TI  - Marker-based or model-based RSA for evaluation of hip resurfacing arthroplasty? A
      clinical validation and 5-year follow-up.
AB  - BACKGROUND: The stability of implants is vital to ensure a long-term survival.
      RSA determines micro-motions of implants as a predictor of early implant failure.
      RSA can be performed as a marker- or model-based analysis. So far, CAD and RE
      model-based RSA have not been validated for use in hip resurfacing arthroplasty
      (HRA). MATERIALS/METHODS: A phantom study determined the precision of marker
      based and CAD and RE model-based RSA on a HRA implant. In a clinical study, 19
      patients were followed with stereoradiographs until 5 years after surgery.
      Analysis of double-examination migration results determined the clinical
      precision of marker-based and CAD model-based RSA, and at the 5-year follow-up,
      results of the total translation (TT) and the total rotation (TR) for marker- and
      CAD model-based RSA were compared. RESULTS: The phantom study showed that
      comparison of the precision (SDdiff) in marker-based RSA analysis was more
      precise than model-based RSA analysis in TT (p CAD < 0.001; p RE = 0.04) and TR
      (p CAD = 0.01; p RE < 0.001). The clinical precision (double examination in 8
      patients) comparing the precision SDdiff was better evaluating the TT using the
      marker-based RSA analysis (p = 0.002), but showed no difference between the
      marker- and CAD model-based RSA analysis regarding the TR (p = 0.91). Comparing
      the mean signed values regarding the TT and the TR at the 5-year follow-up in 13
      patients, the TT was lower (p = 0.03) and the TR higher (p = 0.04) in the marker
      based RSA compared to CAD model-based RSA. INTERPRETATION: The precision of
      marker-based RSA was significantly better than model-based RSA. However, problems
      with occluded markers lead to exclusion of many patients which was not a problem
      with model-based RSA. HRA were stable at the 5-year follow-up. The detection
      limit was 0.2 mm TT and 1 degrees  TR for marker-based and 0.5 mm TT and 1
      degrees  TR for CAD model-based RSA for HRA.

PMID- 24100766
TI  - Increased post-operative ischemia in the femoral head found by microdialysis by
      the posterior surgical approach: a randomized clinical trial comparing surgical
      approaches in hip resurfacing arthroplasty.
AB  - BACKGROUND: Hip resurfacing arthroplasty (HRA) is associated with osteonecrosis
      of the femoral head and femoral neck fracture, which may be caused by a decrease
      in the perfusion of the bone initiated at surgery. Several studies have
      demonstrated a decreased blood flow during surgery depending on the choice of
      surgical approach. We investigated the effect of the surgical approach on the
      blood flow and metabolism in the femoral head and neck in HRA by Laser Doppler
      flowmetry (LDF) and microdialysis. MATERIALS AND METHODS: We conducted a
      randomized clinical trial on 38 patients, allocated to HRA by either the
      posterior (Post) or the antero-lateral (AntLat) surgical approach. LDF was
      performed during surgery and microdialysis after surgery to assess the
      concentration of the following metabolic markers: glucose, lactate, pyruvate and
      glycerol. RESULTS: At 44-50 h after surgery, the mean lactate/pyruvate (L/P) and
      lactate/glucose (L/G) ratio was higher in the Post group compared to the AntLat
      group; L/P 195.3 (SEM 123) in Post and 128.5 (108.0) in AntLat; L/G 16.9 (6.5) in
      Post and 8.9 (3.7) in AntLat (p L/P = 0.02 and p L/G = 0.03). There was no
      difference in the LDF measurements (p = 0.74). INTERPRETATION: HRA in the
      posterior approach results in increased post-operative ischemia in the femoral
      head and neck although during surgery, no difference in the blood flow was found.
      Still, the antero-lateral approach also causes considerable ischemia and other
      possible explanations, such as damage to the retinacular vessels during surgery
      or altered microcirculation because of heating from the cementation process,
      needs to be investigated.

PMID- 24100767
TI  - Muscle strength and function of shoulders with Bankart lesion after successful
      arthroscopic treatment: interlimb comparison 24 months after surgery.
AB  - BACKGROUND: The purpose of this study was to examine outcomes following
      arthroscopic Bankart repair with the focus on strength after the repair. METHODS:
      56 shoulders with Bankart lesion were operated on arthroscopically. Gender,
      mechanism of the first dislocation, number of dislocations, dominant side,
      operated side and the number of anchors used for surgery were recorded. DASH and
      Oxford instability scoring systems were applied preoperatively and compared to
      scores at the 24-month follow-up. The scoring systems were also applied to
      contralateral shoulders at the 24th month of follow-up. Range of motion was
      measured with a goniometer. Muscle strength was analyzed with a dynamometer
      simultaneously with the muscle activity of four perishoulder muscles. The data
      were recorded with surface EMG. Range of motion, muscle strength and activity
      were evaluated according to the contralateral shoulder at the 24th month of
      follow-up. RESULTS: Male/female ratio was 42/14 with a mean age of 32 years. The
      mean number of dislocations was 3 +/- 1 and all were traumatic dislocations. The
      number of mean anchors used was 3.1 and the mean follow-up period was 24 months.
      In clinical evaluation, the preoperative and postoperative results of the DASH
      and Oxford instability scores of the unstable shoulders were significantly
      different. In the comparison between the operated and contralateral shoulders,
      there was no significant difference in DASH and Oxford instability scores at the
      24th month of follow-up. There was no significant loss of range of motion. Only
      internal rotation strength was significantly reduced and there was no significant
      change in the EMG patterns. CONCLUSIONS: Although good clinical results can be
      achieved, internal rotation strength is reduced after arthroscopic surgery, but
      daily activities are not affected. There is no guarantee for patients of
      excellent recovery. LEVEL OF EVIDENCE: Level III cohort study.

PMID- 24100769
TI  - [Innovating in pharmaceutical expenditure management: from payment per product to
      payment for health outcomes].

PMID- 24100768
TI  - Direct in vitro and in vivo comparison of (161)Tb and (177)Lu using a tumour
      targeting folate conjugate.
AB  - PURPOSE: The radiolanthanide (161)Tb (T 1/2 = 6.90 days, Ebeta(-) av = 154 keV)
      was recently proposed as a potential alternative to (177)Lu (T 1/2 = 6.71 days,
      Ebeta(-) av = 134 keV) due to similar physical decay characteristics but
      additional conversion and Auger electrons that may enhance the therapeutic
      efficacy. The goal of this study was to compare (161)Tb and (177)Lu in vitro and
      in vivo using a tumour-targeted DOTA-folate conjugate (cm09). METHODS: (161)Tb
      cm09 and (177)Lu-cm09 were tested in vitro on folate receptor (FR)-positive KB
      and IGROV-1 cancer cells using a 3-(4,5-dimethylthiazol-2-yl)-2,5
      diphenyltetrazolium bromide (MTT) viability assay. In vivo (161)Tb-cm09 and
      (177)Lu-cm09 (10 MBq, 0.5 nmol) were investigated in two different tumour mouse
      models with regard to the biodistribution, the possibility for single photon
      emission computed tomography (SPECT) imaging and the antitumour efficacy.
      Potentially undesired side effects were monitored over 6 months by determination
      of plasma parameters and examination of kidney function with quantitative SPECT
      using (99m)Tc-dimercaptosuccinic acid (DMSA). RESULTS: To obtain half-maximal
      inhibition of tumour cell viability a 4.5-fold (KB) and 1.7-fold (IGROV-1) lower
      radioactivity concentration was required for (161)Tb-cm09 (IC50 ~0.014 MBq/ml and
      ~2.53 MBq/ml) compared to (177)Lu-cm09 (IC50 ~0.063 MBq/ml and ~4.52 MBq/ml).
      SPECT imaging visualized tumours of mice with both radioconjugates. However, in
      therapy studies (161)Tb-cm09 reduced tumour growth more efficiently than (177)Lu
      cm09. These findings were in line with the higher absorbed tumour dose for
      (161)Tb-cm09 (3.3 Gy/MBq) compared to (177)Lu-cm09 (2.4 Gy/MBq). None of the
      monitored parameters indicated signs of impaired kidney function over the whole
      time period of investigation after injection of the radiofolates. CONCLUSION:
      Compared to (177)Lu-cm09 we demonstrated equal imaging features for (161)Tb-cm09
      but an increased therapeutic efficacy for (161)Tb-cm09 in both tumour cell lines
      in vitro and in vivo. Further preclinical studies using other tumour-targeting
      radioconjugates are clearly necessary to draw final conclusions about the future
      clinical perspectives of (161)Tb.

PMID- 24100770
TI  - [Health system sustainability from a network perspective: a proposal to optimize
      healthy habits and social support].
AB  - The search of new health management formulas focused to give wide services is one
      of the priorities of our present health policies. Those formulas examine the
      optimization of the links between the main actors involved in public health, ie,
      users, professionals, local socio-political and corporate agents. This paper is
      aimed to introduce the Social Network Analysis as a method for analyzing,
      measuring and interpreting those connections. The knowledge of people's
      relationships (what is called social networks) in the field of public health is
      becoming increasingly important at an international level. In fact, countries
      such as UK, Netherlands, Italy, Australia and U.S. are looking formulas to apply
      this knowledge to their health departments. With this work we show the utility of
      the ARS on topics related to sustainability of the health system, particularly
      those related with health habits and social support, topics included in the 2020
      health strategies that underline the importance of the collaborative aspects in
      networks. 

PMID- 24100771
TI  - [Process and results of constructing a deprivation index for the districts of
      Madrid and Barcelona, Spain].
AB  - BACKGROUND: There are few economic indicators that take the neighbourhood as the
      unit of reference in our context. The aim of this article is to describe the
      process and results of secondary data collection and development of a deprivation
      index (DI) for the neighbourhoods of the cities of Madrid and Barcelona,
      discussing their utility for research on health inequalities. METHODS: Initial DI
      conceptual framework contained different elements that characterize deprivation
      and for which we collected second-level variables. ID was adapted to the
      availability of variables and to the results of an exploratory analysis. Finally,
      a factor analysis was performed to validate the IP. We built a DI based on five
      dimensions for Madrid (economy, population and territory, housing, cars and
      demographics) and 4 for Barcelona (all except "demographics"). Neighbourhoods
      were grouped into quartiles according to their score for the DI (Q4: higher
      levels of deprivation). Premature mortality rates and premature mortality ratios
      adjusted by age were calculated for each quartile. RESULTS: The IP explained 55%
      of the observed variability in the indicators for Madrid and 69% for Barcelona.
      Premature mortality rate in Madrid for Q1 was 1.65 per 103 in men and 0.92 per
      103 women and 2.81 per 103 in men and 1.22 per 103 in women residing in Q4. In
      Barcelona, the mortality rate was 2.33 per 103 men and 1.15 per 103 women in Q1
      and 3.49 per 103 in men and 1.52 per 103 in women living in Q4. CONCLUSION:
      Premature mortality rates showed higher premature mortality in the most deprived
      districts.

PMID- 24100772
TI  - [Dabigatran versus acenocumarol for the prevention of stroke in atrial
      fibrillation: budget impact analysis in one health department in Spain].
AB  - BACKGROUND: To Estimate, in the context of a Health Department of the Valencia
      Health Agency, the budgetary impact of the widespread use of dabigatran at doses
      of 110 and 150 mg in patients with non-valvular atrial fibrillation (AF),
      regarding the current scenario with acenocoumarol therapy. METHODS: Budget impact
      analysis of three scenarios of oral anticoagulation use in AF: a) current
      treatment with acenocoumarol, b) widespread replacement of acenocoumarol for
      Dabigatran 110 mg and, c) idem at doses of 150 mg. The analysis was conducted
      from the perspective of the Valencia Health Agency with a time horizon of one
      year (2009). The effectiveness and adverse effects were extrapolated from the RE
      LY study, while prevalence and cost data correspond to the Health Department
      estimates in 2009. RESULTS: We included 5889 patients (2.4% of the population >
      18 years) diagnosed with AF, of which 3726 (63.2%) were treated with
      acenocoumarol. The total costs of each scenario were ? 1,119,412 (? 300
      patient/year) for acenocoumarol, ? 4,985,095 (? 1,337 patient/year) for
      dabigatran 110 and ? 4,981,226 (? 1,336 patient/year) for dabigatran 150, with a
      budget impact of 1,037 euros/year per patient shifted from acenocumarol to
      dabigatran-150. CONCLUSIONS: The high budgetary impact of moving to a scenario of
      widespread substitution of warfarin for Dabigatran supports the restriction of
      this therapeutic strategy to subgroups of patients at high risk or difficult
      control.

PMID- 24100773
TI  - [Economic evaluation of rheumathoid arthritis monotherapy with tocilizumab and
      adalimumab].
AB  - BACKGROUND: Tocilizumab (TCZ) was superior to adalimumab (ADA), as monotherapy,
      in reducing signs and symptoms of adult rheumatoid arthritis (RA) when
      methotrexate (MTX) treatment is poorly tolerated or inappropriate. The aim of the
      study was to analyze the cost-effectiveness of TCZ vs ADA in these patients.
      METHODS: Economic evaluation of the cost per response or remission of TCZ vs ADA
      from ADACTA (time horizon: 24 weeks). Clinical response criteria ACR or disease
      remission criteria, DAS28. PERSPECTIVE: National Health System. The costs
      included (acquisition, administration and monitoring of medicines; ? 2012) were
      obtained from Spanish sources. Simple univariate sensitivity analyzes were
      performed. RESULTS: ACR20, ACR50 and ACR70 response rates with TCZ and ADA were
      obtained in 65% and 49.4% (p <0.01), 47.2% and 27.8% (p <0.01); and 32.5% and
      17.9% (p <0.01) of patients, respectively. DAS28 remission occurred in 39.9% and
      10.5%, respectively (p <0.0001). The cost per response was lower with TCZ than
      with ADA (ACR20: ? 8,105 and ? 11,553; ACR50: ? 11,162 and ? 20,529; ACR70: ?
      16,211 and ? 31,882) respectively. The cost of DAS28 remission was ? 13,204 and ?
      54,352, respectively. Treatment with TCZ was dominant (more effective, with lower
      costs vs ADA) in all scenarios analyzed. CONCLUSIONS: According to this analysis,
      in Spain TCZ monotherapy is an efficient strategy vs ADA for treating RA patients
      intolerant to MTX or in which there is inappropriate response.

PMID- 24100774
TI  - [Influence of double workload in perceived health and health services utilization
      of immigrants and Murcian natives, Spain].
AB  - BACKGROUND: Gender inequalities in health have been largely documented. The main
      objective of this study is to assess whether there are gender differences in
      perceived health and health services utilization, and their relation with double
      workload in a representative sample of immigrants and Murcian natives. METHODS:
      We used data from the NHS 2006 and Health and Culture Study, 1,303 immigrants and
      1,303 Spanish, both residents in the Region of Murcia. With the combination of
      reproductive work and paid work we built up the variable 'double workload' (DW).
      We estimated the prevalence ratio (PR) for positive self-perceived health,
      chronic morbidity, activity limitation, doctor's visits, hospitalization,
      emergency and drug use, by origin, using regression methods. Two models were
      constructed by adding double burden to the basic model adjusted by
      sociodemographic variables. Analyses were performed between and within sex.
      RESULTS: After adjusting for DW, no changes were seen in the differences by
      gender [RP women/men of positive perception health: 0.70 (0.54-0.89) East
      European; 0.87 (0.79-0.95) autochthonous / chronic morbidity: 1.44 (1.14-1.82)
      Hispanic; 1.36 (1.19-1.55) autochthonous / activity limitation: 2.23 (1.29-3.83)
      Hispanic; 1.45 (1.01-2.10) autochthonous / doctor's visits: 1.93 (1.50-2.48)
      Hispanic; 1.74 (1.06-2.86) Moroccan; 1.32 (1.09-1.59) autochthonous /
      hospitalization: 1.80 (1.02-3.17) Hispanic], almost the same than unadjusted.
      Women used more drugs than men. Within sexes, both autochthonous men (1.19; 1.06
      1.33) and women (1.18; 1.01-1.40) with shared DW had more positive self-perceived
      health than those without DW. Hispanic men with DW without assistance: 0.67 (0.47
      0.94). CONCLUSIONS: Women have worse health indicators and greater use of health
      services regardless of origin. Consideration of the double workload does not
      explain gender inequalities in health.

PMID- 24100775
TI  - [Discourses on sexual responsibility in a group of HIV-positive MSM in Spain].
AB  - BACKGROUND: High rates of sexual risk behaviours are being reported among HIV
      positive MSM which raises the question about the ideas of sexual responsibility
      that exist in this population to prevent the transmission and/or re-infection of
      HIV and other STIs. This study sought to understand the discourses on sexual care
      and responsibility in men living with HIV who have sex with men. METHODS: A
      qualitative study was carried out with 78 men (aged 27-65): 35 individual
      interviews and 43 in five discussion groups, in the cities of Barcelona, Madrid
      and Palma de Mallorca, between 2007 and 2008. The selection criterion was that
      eighteen months had passed after a HIV diagnosis was established. The grounded
      theory approach was used to analyze the data. RESULTS: Three distinct discourses
      about sexual responsibility were observed: (1) sole responsibility: it is the HIV
      positive man who should protect himself in order to protect others. This
      discourse is based on an ethical position (altruistic), in which the duty and
      obligation to protect others is a priority; (2) shared responsibility: both
      parties agree and/or consent to high risk sexual practices although those who
      tend to use this discourse, in practice, ultimately assume full responsibility,
      and (3) individual responsibility: each person is responsible for himself,
      although the type of emotional bond with others may affect the decision to
      protect only oneself (there is some commitment to protect a sexual partner when
      something is felt for that person). CONCLUSIONS: The sexual care behaviour among
      HIV-positive MSM was determined by three discourses. Those discourses were
      influenced by various factors: moral conscience, sexual context, type of sexual
      partner and disclosure of HIV status.

PMID- 24100776
TI  - [Differences in the nursing consultation utilization in primary care, Spain].
AB  - BACKGROUND: Different conditions in health services utilization may create
      situations of inequity. The objective was analyze the differences of nurse
      consultation utilization in primary care. METHODS: Cross-sectional study, in 23
      health centres in Madrid. Environmental variables, consultation characteristics,
      socio-demographic and health need characteristics were collected. The quality of
      life and satisfaction were also studied. The variables were classified according
      to the "behavioral model" in predisposing, enabling or need variables.
      Explanatory multivariate models were constructed (Generalized-Estimating
      Equations). RESULTS: The higher income areas and aging, predisposing factors,
      were associated with increases of 17% (95% CI: 0.4 to 36.9%) and 11.0% per decade
      (95% CI: 6.2 - 16.2) in nursing consultations per year. Among enabling factors,
      each additional minute of consultation length was associated with an increase of
      2.0% (95% CI :1.2-2, 9%) in number of nurse consultations, each new medical
      consultation was associated with a increase of 2.7% (95% CI: 2.1-3.2%) and the
      delay in getting appointment over a day, represented a decrease of 32.8% (95% CI:
      19.3 to 44.1%) in the total nursing consultations. Each chronic condition, which
      expresses the need health, was associated with an increase in the number of
      visits of 4.8% (95% CI: 1.7 to 8.0%). The improved perception of quality of life
      was associated with a reduction of 5.4% (95% CI 1.0 to 8.7%) of the
      consultations. CONCLUSION: The difference of the use of primary care nurse
      consultations is based on health need criteria, but is also influenced by
      accessibility conditions.

PMID- 24100777
TI  - [Evaluation of process of an educational web-based and mobile phone-based program
      for encouraging healthy behaviours among Spanish and Mexican students].
AB  - BACKGROUND: Current communication technologies can be used in health education.
      The aim was to assess the process of an online program designed to prevent cancer
      risk behaviours using an educational website and mobile phones. METHODS: High
      school students from Spain and Mexico were recruited during 3 academic years
      (2009-12) to participate in a web-based program supplemented with mobile phone
      messages (SMS) which aim was to prevent cancer risk behaviours. The program was
      designed as a randomized trial, with control and experimental group (EG).
      Recruitment and adherence were analyzed using data of the Web management platform
      and Google Analytics. RESULTS: 3,855 students started the logging on the program
      of which 2,001 (51.9%) completed the questionnaire.77.5% were Mexicans, 13 years
      old (40.6%), with good academic level (68.7%) and with parents (49.6%) and
      mothers (53.9%) having university degree. 56.4% recorded a phone number to
      receive SMS. The EG consisted of 1,014 students and the averages of their visits
      to the website were 31.6 in the first year, 21.8 in the second and 21.9 in the
      third. Each adolescent of the EG was able to incorporate 1.16 adults (total
      1,172) and other 1,076 were recorded spontaneously. Retention rate at the end of
      follow-up was 41.5% and was higher among those who were best students (OR: 12,5),
      Mexicans (OR: 4.4), 12 years old (OR: 3.1) and have been incorporated in the
      first three months of the implementation (OR: 2.8). CONCLUSION: Students'
      recruitment and retention was scarce, mainly in Spain. However students involved
      visited the program website with sufficient amount of time to achieve good
      results.

PMID- 24100778
TI  - [Temporal evolution of tobacco consumption among health care workers in a
      Catalonian hospital, Spain].
AB  - BACKGROUND: In terms of tobacco consumption, health workers have been considered
      as reference group, however smoking prevalence in this group is higher than in
      general population. This study aimed to estimate the prevalence of tobacco
      consumption among workers of a health institution in Catalonia during a period of
      10 years (2001-2011), and to describe their characteristics. METHODS: The
      questionnaire on tobacco consumption prevalence was validated, and was
      administered in 2001, 2004, 2008 and 2011. A random sampling was carried out in
      two acute care institutions. The characteristics of the study sample and the
      differences between smokers were analyzed using the chi-square test for linear
      trend. A logistic regression model was performed including all the surveys.
      RESULTS: The smoking prevalence among health care workers for 2001, 2004, 2008
      and 2011, was 30.00%, 34.42%, 36.21% and 29.42%, respectively. Women had the
      highest consumption prevalence (33,40%). Tobacco smoking decreased in medical
      staff, from 25.97% in 2001, to 18.88% in 2011 (p=0.005), and in nurses from
      35,15% in 2001 to 25.61% in 2011 (p=0.007), but not among the administrative
      staff. CONCLUSION: Overall and for the first time, smoking prevalence in health
      workers begins to decrease. However, it does not decrease in the same way among
      all types of healthcare workers and the prevalence remains high when compared
      with the population prevalence. This consumption reduction coincides with the
      measures introduced by the program after the legislative changes.

PMID- 24100779
TI  - [Economic impact of the introduction of a technique for early detection of
      Mycobacterium tuberculosis Complex in clinical samples in a Spanish hospital].
AB  - BACKGROUND: Tuberculosis (TB) remains an important public health problem
      worldwide. Our objective was to estimate the economic and health care impact of
      the introduction of an early diagnosis tecnique of TB, the Xpert MTB/RIF(r) assay
      (Xpert). METHODS: The savings was estimated on the basis of reduction in the time
      of TB hospitalization at avoid the false-negative (FN) and false-positive (FP) TB
      cases diagnosed by auramine staining that could have been detected by Xpert
      between 2008-2012 in our hospital. The costs analysis was made by adding the cost
      arising from FN (hospitalization, special tests and equipment for respiratory
      isolation) and FP (TB treatment, successive medical consultations, analytical and
      microbiological controls). RESULTS: We detected 19 FP and 22 FN during the 5-year
      study. Xpert would have detected 19 FP and 15 FN. It was estimated a minimum cost
      of 3217 euros per FP (treatment, successive medical consultations, analytical and
      microbiological controls), while each FN has required an extension of
      hospitalization from 7 days on average (62229 euros), both translated into a
      global cost of 62229 euros. After an initial investment of 16250 euros (50 cases
      with high suspicion of TB at 65 euros/test), the hospital would have saved 45979
      euros overall in five years. CONCLUSIONS: The introduction of Xpert would improve
      the quality of health care of patients, avoiding both unnecessary
      hospitalizations and treatments. Also, Xpert carries a saving for our hospital.

PMID- 24100780
TI  - Prognostic implications of node metastatic features in OSCC: a retrospective
      study on 121 neck dissections.
AB  - Lymph node metastases are responsible for shorter survival in oral squamous cell
      carcinoma (OSCC). The aim of the present study was to assess the node metastasis
      frequency and survival according to the node metastasis features in 121 neck
      dissections (NDs) performed for OSCC, identifying evidence-based correlations and
      contrasts with previous literature. The retrospective study involved 121 patients
      affected by OSCC who had undergone modified radical ND (MRND) for therapeutic,
      elective reasons or after intraoperative positivity to metastasis of sentinel
      lymph nodes (SLN+). Node metastasis frequency and behaviour (typical vs.
      atypical) and their number and distribution according to pre-surgical cTNM cancer
      staging were considered and overall survival Kaplan-Meier curves were calculated
      for each group in order to compare mortality according to ND type (elective,
      therapeutic, after SLN+), lymph node metastatic pattern (typical or atypical),
      size (micrometastasis vs. macrometastasis) and number. Results showed
      statistically significant different overall survival according to pre-surgical
      staging, number of lymph nodes harvested and intent to surgery. Sentinel lymph
      node resulted in the sole positive node affected by metastasis in small cT1-
      cT2/cN0 OSCC and an ND subsequent to its positivity during intraoperative
      assessment may be considered an overtreatment. 

PMID- 24100781
TI  - Age-dependent accumulation of heavy metals in liver, kidney and lung tissues of
      homing pigeons in Beijing, China.
AB  - Biomonitoring provides direct evidence of the bioavailability and accumulation of
      toxic elements in the environment. In the current study, 1-2, 5-6, and 9-10+ year
      old homing pigeons collected from the Haidian District of Beijing during 2011
      were necropsied and concentrations of cadmium, lead, and mercury were measured in
      liver, lung, and kidney tissue. At necropsy, gray/black discoloration of the
      margins of the lungs was observed in 98 % of the pigeons. There were no
      significant differences in metal concentrations as a function of gender. Cadmium
      concentrations in all tissues and Pb concentrations in the lung tissues were
      significantly greater in 9-10+ year old pigeons compared to other age groups
      indicating that Cd and Pb were bioavailable. Mercury concentrations were not
      significantly different among age groups. Cadmium concentrations in kidney and
      lung tissues of 9-10+ year old pigeons were similar to or exceeded concentrations
      of Cd reported in pigeons from another high traffic urban area and most wild
      avian species from Korea suggesting that Cd in this region of Beijing may be of
      concern. Homing pigeons provide valuable exposure and bioaccumulation data not
      readily available from air monitoring alone, thus providing information regarding
      potential health effects in wildlife and humans in urban areas. As environmental
      quality standards are implemented in China, homing pigeons will serve as a
      valuable bio-monitor of the efficacy of these actions.

PMID- 24100783
TI  - A 2-hour diagnostic protocol for possible cardiac chest pain in the emergency
      department: a randomized clinical trial.
AB  - IMPORTANCE: Patients with chest pain represent a high health care burden, but it
      may be possible to identify a patient group with a low short-term risk of adverse
      cardiac events who are suitable for early discharge. OBJECTIVE: To compare the
      effectiveness of a rapid diagnostic pathway with a standard-care diagnostic
      pathway for the assessment of patients with possible cardiac chest pain in a
      usual clinical practice setting. DESIGN, SETTING, AND PARTICIPANTS: A single
      center, randomized parallel-group trial with blinded outcome assessments was
      conducted in an academic general and tertiary hospital. Participants included
      adults with acute chest pain consistent with acute coronary syndrome for whom the
      attending physician planned further observation and troponin testing. Patient
      recruitment occurred from October 11, 2010, to July 4, 2012, with a 30-day follow
      up. INTERVENTIONS: An experimental pathway using an accelerated diagnostic
      protocol (Thrombolysis in Myocardial Infarction score, 0; electrocardiography;
      and 0- and 2-hour troponin tests) or a standard-care pathway (troponin test on
      arrival at hospital, prolonged observation, and a second troponin test 6-12 hours
      after onset of pain) serving as the control. MAIN OUTCOMES AND MEASURES:
      Discharge from the hospital within 6 hours without a major adverse cardiac event
      occurring within 30 days. RESULTS: Fifty-two of 270 patients in the experimental
      group were successfully discharged within 6 hours compared with 30 of 272
      patients in the control group (19.3% vs 11.0%; odds ratio, 1.92; 95% CI, 1.18
      3.13; P = .008). It required 20 hours to discharge the same proportion of
      patients from the control group as achieved in the experimental group within 6
      hours. In the experimental group, 35 additional patients (12.9%) were classified
      as low risk but admitted to an inpatient ward for cardiac investigation. None of
      the 35 patients received a diagnosis of acute coronary syndrome after inpatient
      evaluation. CONCLUSIONS AND RELEVANCE: Using the accelerated diagnostic protocol
      in the experimental pathway almost doubled the proportion of patients with chest
      pain discharged early. Clinicians could discharge approximately 1 of 5 patients
      with chest pain to outpatient follow-up monitoring in less than 6 hours. This
      diagnostic strategy could be easily replicated in other centers because no extra
      resources are required. TRIAL REGISTRATION: anzctr.org.au Identifier:
      ACTRN12610000766011.

PMID- 24100784
TI  - Localized shear deformation and softening of bulk metallic glass: stress or
      temperature driven?
AB  - Metallic glasses due to their unique combination of physical and chemical
      properties have a great potential in various applications: materials for
      construction, medical, MEMs devices and so on. The deformation mechanism in
      metallic glasses is very much different from that in conventional crystalline
      materials and not yet fully understood. Here we are trying to find out what
      drives shear deformation in metallic glasses. The compression experiments of the
      bulk metallic glassy (BMG) samples coated with tin, Rose metal and indium were
      performed. There were no melting sites of the coating observed near individual
      shear bands. Melting occurred only near fracture surface, near microcracks and in
      the places of shear band concentrations. The results indicate that shear banding
      is rather a stress driven process while the temperature rise that was observed
      takes place due to friction forces in the viscous supercooled liquid thin layer
      in the shear bands. 

PMID- 24100782
TI  - Characterising metabolically healthy obesity in weight-discordant monozygotic
      twins.
AB  - AIMS/HYPOTHESIS: Not all obese individuals display the metabolic disturbances
      commonly associated with excess fat accumulation. Mechanisms maintaining this
      'metabolically healthy obesity' (MHO) are as yet unknown. We aimed to study
      different fat depots and transcriptional pathways in subcutaneous adipose tissue
      (SAT) as related to the MHO phenomenon. METHODS: Sixteen rare young adult obesity
      discordant monozygotic (MZ) twin pairs (intra-pair difference (?) in BMI >= 3
      kg/m(2)), aged 22.8-35.8 years, were examined for detailed characteristics of
      metabolic health (subcutaneous, intra-abdominal and liver fat [magnetic resonance
      imaging/spectroscopy]), OGTT, lipids, adipokines and C-reactive protein (CRP).
      Affymetrix U133 Plus 2.0 chips were used to analyse transcriptomics pathways
      related to mitochondrial function and inflammation in SAT. RESULTS: Based on
      liver fat accumulation, two metabolically different subgroups emerged. In half
      (8/16) of the pairs (?weight 17.1 +/- 2.0 kg), the obese co-twin had
      significantly higher liver fat (?718%), 78% increase in AUC insulin during OGTT
      and CRP, significantly more disturbance in the lipid profile and greater tendency
      for hypertension compared with the lean co-twin. In these obese co-twins, SAT
      expression of mitochondrial oxidative phosphorylation, branched-chain amino acid
      catabolism, fatty acid oxidation and adipocyte differentiation pathways were
      downregulated and chronic inflammation upregulated. In the other eight pairs
      (?weight 17.4 +/- 2.8 kg), the obese co-twin did not differ from the non-obese co
      twin in liver fat (?8%), insulin sensitivity, CRP, lipids, blood pressure or SAT
      transcriptomics. CONCLUSIONS/INTERPRETATION: Our results suggest that maintenance
      of high mitochondrial transcription and lack of inflammation in SAT are
      associated with low liver fat and MHO.

PMID- 24100785
TI  - An open-label, randomized, controlled trial of zotepine and risperidone for
      acutely ill, hospitalized, schizophrenic patients with symptoms of agitation.
AB  - Acutely ill, schizophrenic patients frequently require management of agitation.
      This study was conducted to compare the efficacy of oral zotepine and risperidone
      in hospitalized, acutely ill schizophrenic patients with symptoms of
      agitation.This was a 6-week, multicenter, randomized, open-label, parallel-group,
      flexible dosing study. Thirty-nine patients with schizophrenia (Diagnostic and
      Statistical Manual of Mental Disorders, Fourth Edition) who met the criteria of a
      Positive and Negative Syndrome Scale (PANSS) total score of greater than or equal
      to 60 points, PANSS-excitement component (EC) score of greater than or equal to
      14 points, and at least 1 PANSS-EC score of greater than or equal to 4 were
      randomly assigned to either the zotepine or risperidone group. The primary
      outcome was a comparison of the change in the PANSS-EC total score from baseline
      to the end of the study between groups.There was no significant between-group
      difference in dropout rates (zotepine, 15.8% [3/19]; risperidone, 20.0% [4/20]).
      The mean (SD) daily dose of zotepine from baseline to study end point ranged from
      127.6 (62.3) to 236.8 (74.2) mg/d; the corresponding values for risperidone
      ranged from 3.3 (1.6) to 4.8 (1.7) mg/d. There were no statistically significant
      differences in patient characteristics, PANSS total score, and PANSS-EC total
      score between the zotepine and risperidone groups at baseline. Both groups showed
      significant reductions in the PANSS-EC total scores (zotepine, -10.1 [4.7], P <
      0.001; risperidone, -8.0 [5.3], P < 0.001) and PANSS total scores (zotepine, 
      34.7 [15.8], P < 0.001; risperidone, -28.6 [14.3], P < 0.001). However, there
      were no significant differences in PANSS-EC total score (P = 0.265) and PANSS
      total score (P = 0.125) changes from baseline to study end point between the 2
      treatment groups. Serum uric acid and prolactin decreased more in the zotepine
      group than the risperidone group (P < 0.001 and P = 0.018, respectively).Zotepine
      seemed to be as effective as risperidone in treating hospitalized, acutely ill,
      schizophrenic patients with agitation, and had the advantages of lowering
      hyperuricemia and hyperprolactinemia. Double-blind, fixed dose studies with a
      larger sample size of acutely ill, schizophrenic patients with agitation are
      needed to confirm the study results. 

PMID- 24100786
TI  - Acute effects of single-dose olanzapine on metabolic, endocrine, and inflammatory
      markers in healthy controls.
AB  - Atypical antipsychotics may "directly" influence glucose homeostasis, increasing
      risk of type 2 diabetes independently of changes in adiposity. Animal models
      suggest direct effects after even a single dose of certain atypical
      antipsychotics on glucose dysregulation. Here, we investigated effects of a
      single-dose olanzapine (OLA) on glucose metabolism in healthy volunteers, thereby
      minimizing confounding effects of the illness of schizophrenia and adiposity. In
      a randomized double-blind crossover design, 15 subjects were administered 10 mg
      of OLA or placebo at 7:00 A.M. on separate study dates. A frequently sampled
      intravenous glucose tolerance test was initiated 4.25 hours later to assess
      changes in glucose homeostasis, including an index of insulin sensitivity,
      disposition index, glucose effectiveness, and acute insulin response to glucose.
      We also examined effects on cortisol, prolactin, fasting free fatty acids (FFAs),
      insulin-mediated suppression of FFAs, and adipocytokines (leptin, adiponectin, C
      reactive protein, interleukin 6, and tumor necrosis factor alpha). Complete data
      for both visits were analyzed for 12 subjects. Olanzapine treatment significantly
      decreased glucose effectiveness (P = 0.041) and raised fasting glucose over 4.25
      hours (P = 0.03) as compared to placebo. Olanzapine was associated with lower
      serum cortisol (P = 0.003), lower fasting FFA (P = 0.042), and increased
      prolactin levels (P < 0.0001). We therefore suggest that a single dose of OLA may
      invoke early changes in some parameters of glucose and lipid metabolism, as well
      as endocrine indices. 

PMID- 24100787
TI  - Use of mental health telemetry to enhance identification and predictive value of
      early changes during augmentation treatment of major depression.
AB  - Standard clinical trial methodology in depression does not allow for careful
      examination of early changes in symptom intensity. The purpose of this study was
      to use daily "Mental Health Telemetry" (MHT) to prospectively record change in
      depressive and anxiety symptoms for depressed patients receiving augmentation
      treatment, and determine the extent and predictive capacity of early changes. We
      report results of a 6-week, open-label study of the addition of quetiapine XR
      (range, 50-300 mg) for adult patients (n = 26) with major depressive disorder who
      were nonresponsive to antidepressant treatment. In addition to regular study
      visits, all participants completed daily, wirelessly transmitted self-report
      ratings of symptoms on a Smartphone. Daily and 3-day moving average mean scores
      were calculated, and associations between early symptom change and eventual
      response to treatment were determined. Improvement in depressive and anxiety
      symptoms was identified as early as day 1 of treatment. Of the total decline in
      depression severity over 6 weeks, 9% was present at day 1, 28% at day 2, 39% at
      days 3 and 4, 65% at day 7, and 80% at day 10. Self-report rating of early
      improvement (>=20%) in depressive symptoms at day 7 significantly predicted
      responder status at week 6 (P = 0.03). Clinician-rated depressive and anxiety
      symptoms only became significantly associated with responder status at day 14. In
      conclusion, very early changes in depressive symptoms were identified using MHT,
      early changes accounted for most of total change, and MHT-recorded improvement as
      early as day 7 significantly predicted response to treatment at study end point. 

PMID- 24100788
TI  - PET measurement of receptor occupancy as a tool to guide dose selection in
      neuropharmacology: are we asking the right questions?
AB  - Receptor occupancy studies are becoming commonplace for verifying drug mechanism
      of action and selecting early development candidates. Positron emission
      tomography (PET) has been applied to pharmacodynamic (PD) studies in several
      therapeutic areas including neurology, cardiology, and oncology. Prospective use
      of PET to define dosing requirements has been proposed particularly for central
      nervous system (CNS)-targeted drugs; however, correlations with clinical outcomes
      have been mostly anecdotal and not causally established.

PMID- 24100790
TI  - Macromolecular semi-rigid nanocavities for cooperative recognition of specific
      large molecular shapes.
AB  - Molecular shape recognition for larger guest molecules (typically over 1 nm) is a
      difficult task because it requires cooperativity within a wide three-dimensional
      nanospace coincidentally probing every molecular aspect (size, outline shape,
      flexibility and specific groups). Although the intelligent functions of proteins
      have fascinated many researchers, the reproduction by artificial molecules
      remains a significant challenge. Here we report the construction of large, well
      defined cavities in macromolecular hosts. Through the use of semi-rigid dendritic
      phenylazomethine backbones, even subtle differences in the shapes of large guest
      molecules (up to ~2 nm) may be discriminated by the cooperative mechanism. A
      conformationally fixed complex with the best-fitting guest is supported by a
      three-dimensional model based on a molecular simulation. Interestingly, the
      simulated cavity structure also predicts catalytic selectivity by a ruthenium
      porphyrin centre, demonstrating the high shape persistence and wide applicability
      of the cavity. 

PMID- 24100793
TI  - Kinetic model-based feed-forward controlled fed-batch fermentation of
      Lactobacillus rhamnosus for the production of lactic acid from Arabic date juice.
AB  - Arabic date is overproduced in Arabic countries such as Saudi Arabia and Iraq and
      is mostly composed of sugars (70-80 wt%). Here we developed a fed-batch
      fermentation process by using a kinetic model for the efficient production of
      lactic acid to a high concentration from Arabic date juice. First, a kinetic
      model of Lactobacillus rhamnosus grown on date juice in batch fermentation was
      constructed in EXCEL so that the estimation of parameters and simulation of the
      model can be easily performed. Then, several fed-batch fermentations were
      conducted by employing different feeding strategies including pulsed feeding,
      exponential feeding, and modified exponential feeding. Based on the results of
      fed-batch fermentations, the kinetic model for fed-batch fermentation was also
      developed. This new model was used to perform feed-forward controlled fed-batch
      fermentation, which resulted in the production of 171.79 g l(-1) of lactic acid
      with the productivity and yield of 1.58 and 0.87 g l(-1) h(-1), respectively.

PMID- 24100791
TI  - Improvement in thermostability of metagenomic GH11 endoxylanase (Mxyl) by site
      directed mutagenesis and its applicability in paper pulp bleaching process.
AB  - An attempt has been made for enhancing the thermostability of xylanase (Mxyl)
      retrieved from a compost-soil-based metagenomic library. The analysis of the
      structure of xylanase by molecular dynamics simulation revealed more structural
      fluctuations in beta-sheets. When the surface of beta-sheets was enriched with
      arginine residues by substituting serine/threonine by site-directed mutagenesis,
      the enzyme with four arginine substitutions (MxylM4) exhibited enhanced
      thermostability at 80  degrees C. The T 1/2 of MxylM4 at 80  degrees C, in the
      presence of birchwood xylan, increased from 130 to 150 min at 80  degrees C
      without any alteration in optimum pH and temperature and molecular mass.
      Improvement in thermostability of MxylM4 was corroborated by increase in T m by 6
      degrees C over that of Mxyl. The K m of MxylM4, however, increased from 8.01 +/-
      0.56 of Mxyl to 12.5 +/- 0.32 mg ml(-1), suggesting a decrease in the affinity as
      well as specific enzyme activity. The Mxyl as well as MxylM4 liberated
      chromophores and lignin-derived compounds from kraft pulp, indicating their
      applicability in pulp bleaching. 

PMID- 24100792
TI  - Effect of metformin on residual cells after chemotherapy in a human lung
      adenocarcinoma cell line.
AB  - Cancer chemotherapy, including molecular targeted therapy, has major limitations
      because it does not kill all the cancer cells; the residual cells survive until
      they acquire chemoresistance. In the present study, the combined effects of
      metformin and gefitinib were examined in vivo in a mouse xenograft model,
      inoculated with a human lung adenocarcinoma cell line that possesses an
      activating epidermal growth factor receptor mutation. The mechanism of the
      interaction was further elucidated in vitro. Metformin did not suppress the
      growth of already established tumors, nor did metformin augment tumor shrinkage
      by gefitinib. However, metformin significantly suppressed the regrowth of the
      tumor after effective treatment with gefitinib, suggesting the specific effect of
      metformin on the residual cells. Cytotoxicity of metformin was characterized by
      the absence of apoptosis induction and unremarkable cell cycle shift in vitro.
      The residual cell population after treatment with gefitinib was characterized by
      enriched cells with high expression of CD133 and CD24. Metformin was still
      effective on this specific cell population. Targeting residual cells after
      chemotherapy may represent an effective novel strategy for the treatment of
      cancer. Elucidating the mechanism of metformin cytotoxicity provides insights
      into future development of anticancer therapeutics. 

PMID- 24100794
TI  - Controversies over the diagnosis of oligodendroglioma: a report from the
      satellite workshop at the 4th international symposium of brain tumor pathology,
      Nagoya Congress Center, May 23, 2012.
AB  - With the goal of discussing how the neuropathology community should resolve the
      controversy over the diagnosis of oligodendroglioma, this Satellite Workshop
      reflects the collaboration between two invited keynote speakers: Dr. Johan M.
      Kros of the Erasmus Medical Center and Dr. Kenneth D. Aldape of the University of
      Texas MD Anderson Cancer Center and the Organizing Committee of the Japanese
      Society of Brain Tumor Pathology. In the first half of the workshop, the keynote
      speakers reviewed the current status of the pathology and genetics of
      oligodendroglioma. In the second half, six debatable cases that exemplify the
      current controversies over the diagnosis of oligodendroglioma were presented. The
      consensus diagnoses in these six cases, which have been reviewed by members of
      the Society, were opened to discussion and comments by the speakers. These cases
      highlight unresolved issues in the WHO 2007 classification of oligodendrogliomas,
      particularly the discordance between morphology and genetics. To achieve
      synchronization between phenotypes and genotypes, the neuropathology diagnosis
      should focus on the classic features of oligodendrogliomas that are highly
      correlated with the genetic background.

PMID- 24100795
TI  - Role of PPARs in inflammatory processes associated with metabolic syndrome
      (Review).
AB  - Metabolic syndrome (MS) includes the presence of arterial hypertension, insulin
      resistance, dyslipidemia, cardiovascular disease (CVD) and abdominal obesity,
      which is associated with a chronic inflammatory response, characterized by
      abnormal adipokine production, and the activation of certain pro-inflammatory
      signaling pathways. Furthermore, the changes presented by the adipose tissue in
      MS favors the secretion of several molecular mediators capable of activating or
      suppressing a number of transcription factors, such as the peroxisome
      proliferator-activated receptors (PPARs), whose main functions include storage
      regulation and fatty acid catabolization. When they are activated by their
      ligands (synthetic or endogenous), they control several genes involved in
      intermediate metabolism, which make them, together with the PPAR gamma
      coactivator-1-alpha (PGC-1) and the silent information regulator T1 (SIRT1), good
      targets for treating metabolic diseases and their cardiovascular complications. 

PMID- 24100798
TI  - Spatial distribution and concentration assessment of total petroleum hydrocarbons
      in the intertidal zone surface sediment of Todos os Santos Bay, Brazil.
AB  - The primary objective of this study was to investigate the concentrations and
      spatial distribution of the total petroleum hydrocarbons (TPHs) in the intertidal
      zone surface sediment of Todos os Santos Bay, Brazil, to assess the distribution
      and degree of contamination by TPHs, measure the level of TPH degradation in the
      surface sediment, and identify the organic matter sources. The surface sediment
      used in this study was collected in 50 stations, and TPHs, isoprenoid alkanes
      (pristane and phytane), and unresolved complex mixture (UCM) were analyzed by gas
      chromatography with a flame ionization detector. The total concentrations ranged
      from 0.22 to 40,101 MUg g(-1) dry weight and showed a strong correlation with the
      total organic carbon (TOC) content. The highest TPH concentrations were observed
      in samples from the mangrove sediments of a river located near a petroleum
      refinery. Compared with other studies in the world, the TPH concentrations in the
      intertidal surface sediment of Todos os Santos Bay were below average in certain
      stations and above average in others. An analysis of the magnitude of UCM (0.11
      to 17,323 MUg g(-1) dry weight) and the ratios nC17/Pr and nC18/Ph suggest that
      an advanced state of oil weathering, which indicates previous contamination. The
      molar C/N ratios varied between 5 and 43, which indicate organic matter with a
      mixed origin comprising marine and continental contributions. 

PMID- 24100799
TI  - Monitoring diel dissolved oxygen dynamics through integrating wavelet denoising
      and temporal neural networks.
AB  - Diel dissolved oxygen (DO) time series measured continuously using proximal
      sensors in situ for a temperate lake were denoised using discrete wavelet
      transform (DWT) with the orthogonal wavelet families of coiflet, daubechies, and
      symmlet with order of 10. Diel DO time series denoised were modeled using nine
      temporal artificial neural networks (ANNs) as a function of water level, water
      temperature, electrical conductivity, pH, day of year, and hour. Our results
      showed that time-lag recurrent network (TLRN) using denoised data emulated diel
      DO dynamics better than the best-performing TLRN using the original data, time
      delay neural network (TDNN), and recurrent network (RNN). Daubechies basis dealt
      with diel DO data slightly better than the other bases given its coefficient of
      determination (r (2) = 87.1 %), while symmlet performed slightly better than the
      other bases in terms of root mean square error (RMSE = 1.2 ppm) and mean absolute
      error (MAE = 0.9 ppm). 

PMID- 24100800
TI  - Abdominopelvic tuberculosis mimicking advanced ovarian cancer and pelvic
      inflammatory disease: a series of 28 female cases.
AB  - OBJECTIVE: To present and discuss 28 female cases with abdominopelvic
      tuberculosis (TB) and abnormal CA125 levels to better distinguish this disease
      from advanced ovarian cancer (AOC) and pelvic inflammatory disease (PID).
      Abdominopelvic tuberculosis (APTB) is one of the extrapulmonary tuberculosis (TB)
      sites, usually misdiagnosed as AOC and PID and then has to undergo surgery.
      However, the treatment of APTB is totally based on medical therapy other than
      surgery except biopsy. This article aims to present and discuss 28 female APTB
      cases with abnormal CA125 levels to better distinguish this disease from AOC and
      PID so as to find out non-invasive APTB diagnosis methods. METHODS: 28 APTB
      patients diagnosed between January 2000 and January 2010 in our gynecologic
      department of Nanjing Jinling hospital were reviewed retrospectively and compared
      with AOC and PID. RESULTS: The mean age was 38.24 +/- 11 (range 15-64) years.
      Elevated levels of serum CA125 were determined in all 28 patients (100%). Other
      common findings were ascites in 20 (71.43%, 20/28), pelvic mass in 21(75%,
      21/28), slight fever with night sweat in 13 (46.43%, 13/28), cough and pleural
      effusion in nine (32.14 %, 9/28), high fever more than 39  degrees C combined
      with abdominal pain and elevated white blood count in five (17.86%, 5/28), weight
      loss more than 5 kg at admission in six (21.43%, 6/28). Diagnoses were made based
      on biopsy from laparotomy in 14 (50%) patients, from laparoscopy in nine
      (32.14%), from diagnostic curettage because of primary infertility in two
      (7.14%), and only from clinical suspicion in three patients. Histopathology
      revealed that caseating granulomatous lesions were seen in 25 patients, positive
      anti-acid staining in 11 patients. Totally 26 patients completed anti-TB therapy
      successfully and were cured, two patients died of the disease because of long
      term immune inhibitor used. CONCLUSION: Although it is difficult to exactly
      distinguish APTB from AOC and PID without operation, it is important because the
      treatment of APTB is totally based on medical therapy other than surgery. Some
      difference may be found out if clinical manifestation, physical examination,
      laboratory tests and imaging findings are carefully analyzed to avoid unnecessary
      extensive surgery and improve the prognosis.

PMID- 24100801
TI  - Revisiting the pathogenesis of ovarian cancer: the central role of the fallopian
      tube.
AB  - BACKGROUND: Among all gynecological malignancies, ovarian cancer is associated
      with the highest rate of mortality. Recent findings now propose a pivotal role
      for the fallopian tube during ovarian cancer pathogenesis. NEW INSIGHTS: Until
      recently, ovarian cancer was thought to derive from the ovarian surface
      epithelium. Nevertheless, attempts to define a precursor lesion from this tissue
      failed. Instead, prophylactic surgery performed on BRCA mutation carriers and
      subsequent histological analyses revealed a characteristic pre-neoplastic
      alteration at the fimbriated end of the fallopian tubes, the so-called serous
      tubal intraepithelial carcinoma (STIC). By morphology and molecular genetics,
      STIC was found to resemble serous ovarian cancer. As STIC can also be detected in
      >60 % of BRCA-unrelated serous ovarian carcinomas, it is now considered to be the
      precursor of the most common ovarian cancer subtype. CONSEQUENCES: Based on this
      hypothesis, a salpingectomy, i.e., the removal of the post-reproductive fallopian
      tubes may remove the actual site of tumorigenesis and thereby prevent spreading
      over the ovarian surface and throughout the peritoneum. Consequently,
      prophylactic salpingectomy might protect against serous ovarian cancer. Moreover,
      the procedure interrupts the connection between the uterine cavity and the lesser
      pelvis. Hence, it prevents the ascension of exfoliated endometrial cells which
      will likely reduce the incidence of endometrioid and clear cell ovarian cancers.
      Increasing evidence suggests that serous ovarian cancer originates from the
      fimbriated distal end of the fallopian tube, whereas the ovary gets only involved
      at a later stage. CONCLUSION: Given the lack of suitable screening or early
      detection strategies for ovarian cancer, post-reproductive salpingectomy deserves
      serious consideration as a prophylactic intervention that will likely confer
      significant protection against an often deadly disease.

PMID- 24100802
TI  - Platelet-derived growth factor BB mediates the glioma-induced migration of bone
      marrow-derived mesenchymal stem cells by promoting the expression of vascular
      cell adhesion molecule-1 through the PI3K, P38 MAPK and NF-kappaB pathways.
AB  - Platelet-derived growth factor BB (PDGFBB) has been shown to activate the
      migration of bone marrow-derived mesenchymal stem cells (BM-MSCs), and to
      contribute to mediating the tropism of BM-MSCs towards gliomas. However, the
      exact mechanism of this migratory behavior remains to be elucidated. The present
      study investigated the role of vascular cell adhesion molecule-1 (VCAM-1) in the
      PDGFBB-induced migration of BM-MSCs, the effect of PDGFBB on VCAM-1 expression of
      BM-MSCs and related signaling pathways involved in this process. Rat BM-MSCs were
      isolated and cultured by their characteristics of adherence to plastics. The
      concentrations of PDGFBB in the conditioned medium of C6 and U87 cells were
      measured using the ELISA method. In vitro migration assays using a VCAM-1
      blocking antibody were performed to evaluate the role of VCAM-1 in PDGFBB-induced
      migration of BM-MSCs. The effect of rat recombinant PDGFBB on VCAM-1 expression
      of BM-MSCs was studied by RT-PCR and western blotting. LY294002, SB203580,
      PD98059, SP600125 and BAY11-7082 were used to explore the role of PI3K, p38 MAPK,
      MEK, JNK and NF-kappaB in the related intracellular signal transduction of PDGFBB
      stimulation on VCAM-1 expression of BM-MSCs. The data demonstrated that the
      neutralization of VCAM-1 inhibited the migration of BM-MSCs induced by PDGFBB.
      Additionally, PDGFBB stimulation increased VCAM-1 expression of BM-MSCs, which
      could be inhibited by LY294002, SB203580 and BAY11-7082. It is reasonable to
      conclude that PDGFBB significantly enhanced the expression of VCAM-1 in BM-MSCs,
      which facilitated the migration of BM-MSCs towards PDGFBB. PI3K, p38 MAPK and NF
      kappaB were involved in the signal transduction of this process.

PMID- 24100803
TI  - Code black: a natural disaster.

PMID- 24100806
TI  - Interferon gamma-release assays for diagnosis of latent tuberculosis in
      healthcare workers in low-incidence settings: pros and cons.

PMID- 24100805
TI  - Cardiovascular disease risk prediction in women: is there a role for novel
      biomarkers?
AB  - BACKGROUND: Risk prediction is an integral part of the current US guidelines for
      cardiovascular disease in women. Although current risk prediction algorithms
      exist to identify women at increased 10-year risk of cardiovascular disease
      (CVD), clinicians and researchers have been interested in developing novel
      biomarkers that might improve predictive accuracy further. These biomarkers have
      led to important insights into the pathophysiology of CVD, but results for their
      ability to improve prediction or guide preventive therapy have been mixed. The
      incidence of CVD is lower in women than men, and the effects of a number of
      traditional biomarkers on CVD risk differ in women compared to men. Both of these
      factors influence the ability to accurately predict CVD risk. CONTENT: We review
      the distinctive aspects of CVD risk prediction in women, discuss the statistical
      challenges to improved risk prediction, and discuss a number of biomarkers in
      varying stages of development with a range of performance in prediction. SUMMARY:
      A variety of biomarkers from different pathophysiologic pathways have been
      evaluated for improving CVD risk. While many have been incompletely studied or
      have not been shown to improve risk prediction in women, others, such as high
      sensitivity troponin T, have shown promise in improving risk prediction.
      Increasing inclusion of women in CVD studies will be crucial to providing
      opportunities to evaluate future biomarkers.

PMID- 24100807
TI  - Epitope specificity of anti-cardiac troponin I monoclonal antibody 8I-7.

PMID- 24100804
TI  - Clinical evaluation of systemic and local immune responses in cancer: time for
      integration.
AB  - The immune system has a dual role in cancer development and progression. On the
      one hand, it can eradicate emerging malignant cells, but on the other hand, it
      can actively promote growth of malignant cells, their invasive capacities and
      their ability to metastasize. Immune cells with predominantly anti-tumor
      functionality include cells of the innate immune system, such as natural killer
      cells, and cells of adaptive immunity, such as conventional dendritic cells and
      cytotoxic T lymphocytes. Immune cells with predominantly pro-tumor functionality
      include a broad spectrum of cells of the innate and adaptive immune system, such
      as type 2 neutrophils and macrophages, plasmacytoid DC, myeloid-derived
      suppressor cells and regulatory T lymphocytes. The presence of immune cells with
      tumor-suppressive and tumor-promoting activity in the cancer microenvironment and
      in peripheral blood is usually associated with good clinical outcomes and poor
      clinical outcomes, respectively. Significant advances in experimental and
      clinical oncoimmunology achieved in the last decade open an opportunity for the
      use of modern morphologic, flow cytometric and functional tests in clinical
      practice. In this review, we describe an integrated approach to clinical
      evaluation of the immune status of cancer patients for diagnostic purposes,
      prognostic/predictive purposes (evaluation of patient prognosis and response to
      treatment) and for therapeutic purposes. 

PMID- 24100808
TI  - Digital PCR as a novel technology and its potential implications for molecular
      diagnostics.

PMID- 24100809
TI  - [Development and exercise of rights in sexual and reproductive health].

PMID- 24100810
TI  - [Characteristics of violence during teenage pregnancy in Lima, Peru].
AB  - OBJECTIVES: To determine the characteristics of violence seen in pregnant
      teenagers who were treated at the Instituto Nacional Materno Perinatal (INMP) in
      Lima, Peru. MATERIALS AND METHODS: A cross-sectional study was carried out by
      INMP between January and March, 2010 using a probabilistic and systematic
      sampling. The study unit comprises every hospitalized teenager who had just given
      birth and who lived in Lima. A semi-structured interview was conducted. History
      of violence was operationalized into: verbal violence (insults, ridicule, and
      humiliation), physical violence (arm pulling, hair pulling, pushes), direct
      aggression (slaps, kicking, burns) and sexual violence (sexual intercourse
      without consent). RESULTS: 292 teenage mothers aged 16,5 +/- 1 in average took
      part in the study. 47.9% lived with their partners and 51.4% were single. In
      97.3% of the cases, they got pregnant as a result of a conserted sexual
      relationship, while 2.7% got pregnant as a result of rape. 90.1% of teenage
      mothers reported not having planned the pregnancy. Conserning history of
      violence: 48.1% had had verbal violence, 17.1% physical violence, 8.2% direct
      aggression and 6.8% sexual violence. CONCLUSIONS: Violence during teenage
      pregnancy is not an isolated event; actually, it is rather common in any of its
      forms.

PMID- 24100811
TI  - [Influence of voluntary military service on the sexual behavior of a population
      of young adults].
AB  - OBJECTIVES: To determine if having done the voluntary military service is related
      to the sexual behavior of a population of young adults. MATERIALS AND METHODS: A
      cross-sectional study was carried out, which involved cadets enrolled in the
      Peruvian Air Force Sub Officer Academy of Peru, in 2010. For this study,
      civilians, as well as personnel who had performed voluntary military service,
      anonymously answered a self-administered questionnaire about their knowledge
      regarding HIV transmission and sexual risk behaviors. RESULTS: 124 male
      participants took part in the study. 19.4% had performed voluntary military
      service and 80.6% were civilians. Those cadets who had performed voluntary
      military service knew more about HIV transmission than the civilians (p=0.04).
      Likewise, the former also had more occasional sexual partners in the last 12
      months (p=0.04), number that doubled that of the civil personnel. Cadets with a
      record of voluntary military service informed to have consumed three times as
      much alcohol before their last sexual contact in comparison to the civilians
      (p=0.06). According to UNAIDS's definition, having performed voluntary military
      services was not a predictor of sexual risk behavior. CONCLUSIONS: Having
      performed voluntary military service was associated with having a better
      knowledge of HIV transmission. On the other hand, it seems to be related to
      having a higher number of occasional sexual partners. Finally, it was not found
      to be related to sexual risk behaviors.

PMID- 24100812
TI  - [Lead levels in pregnant women and newborns in la Oroya City, Peru].
AB  - OBJECTIVES: To determine blood-lead (Pb) levels in pregnant women and neonates in
      a metallurgical city of Peru. MATERIALS AND METHODS: A cross-sectional study was
      carried out, the population of which consisted of pregnant women who had lived
      for at least two years in the city of La Oroya, at the time when the lead, copper
      and zinc foundries operated normally. A blood sample was obtained from the
      pregnant women before delivery and, after delivery, from the neonate's umbilical
      cord and placenta. Lead levels in those samples were measured by graphite furnace
      atomic absorption spectrophotometry. Pearson's squared regressions and
      correlations were determined. RESULTS: Forty normal deliveries were studied. The
      average blood lead levels in the mother, umbilical cord and placenta were 27.4 +/
      15.6 ug/dL; 19.0 +/- 12.6 ug/dL and 319.0 +/- 215.9 ug/100 g, respectively.
      67.5% of the neonates registered levels higher than 10 ug/dL. Pb levels in the
      umbilical cord accounted for 69.4% of Pb level in maternal blood. The correlation
      coefficients between Pb levels in maternal blood and umbilical cord, maternal
      blood and placenta, and placenta and umbilical cord were 0.36; 0.48 and 0.33,
      respectively. CONCLUSIONS: At the time the foundry operated, pregnant women and
      newborns had high blood lead concentrations. Pb concentrations in the placenta
      and umbilical cord had moderate correlation with the Pb levels in maternal blood.
      Pb levels in maternal blood and umbilical cord were 1.5 times as high as in more
      distant areas.

PMID- 24100813
TI  - [Weight status and cardiorespiratory fitness in school students in the central
      region of Peru].
AB  - OBJECTIVES: To determine the frequency of overweight and obesity in relation to
      cardiorespiratory fitness (CRF) levels in school students in 4 districts of the
      central region of Peru, and to analyze the relations among these variables.
      MATERIALS AND METHODS: Weight, height and CRF were evaluated in 7841 school
      students who reside in four districts located on the coast, in the highlands and
      in the jungle of the central region of the country. Overweight and obesity were
      classified according to the criteria proposed by Cole. CRF was evaluated by a 12
      minute run/walk test taken from the American Alliance for Health, Physical
      Education, Recreation and Dance's test battery. ANOVA and logistic regression
      were used to examine the differences of the averages and the associations among
      these variables. RESULTS: Both male and female school students have similar
      frequency of overweight and obesity (20.9% in women and 20.1% in men). Residents
      of the coast (Barranco) presen thigh frequency of overweight and obesity (37.8%).
      Age, sex, geographical area and CRF were significant predictors of overweight and
      obesity. School students who live in Barranco are five times more likely to be
      obese (OR=4.67; CI95%: 3.55-6.14), while those who reside in the highlands
      (Junin) are less likely to be obese (OR=0.03; CI95%: 0.01-0.20). Furthermore, in
      contrast with students with high CRF, those with low CRF are more likely to be
      obese (OR=11.82; CI95%: 7.25-19.27). CONCLUSIONS: There was a high frequency of
      overweight and obesity among school students who reside in Barranco. Low CRF is
      associated with overweight and obesity.

PMID- 24100814
TI  - [Criminal claims about medical professional liability in the Instituto de
      Medicina Legal of Lima, Peru].
AB  - OBJECTIVES: To determine the characteristics of the criminal complaints claining
      medical professional liability, based on the expert reports issued by the
      Forensic Examination Division of Lima, Peru. MATERIALS AND METHODS: A cross
      sectional study was carried out, which included all the expert reports issued
      between 2005 and 2010 at the Forensic Examination Division of Lima, Peru. A
      descriptive analysis of each of the variables was performed. RESULTS: 60.3%
      (495/821) of the criminal complaints for medical professional liability were
      valued as being in accordance with the lex artis while 16.8% (138/821) were not
      in accordance with the lex artis. In 13% (107/821) of the cases, conclusions
      could not be drawn;in 9.9% (81/821) of the cases, the conclusions in the expert
      report did not include an valuations of the medical act.The cases in which the
      injury was attributed to the process of the disease itself accounted for 80.9%
      (502/620), and those in which in the injury was considered a result of the health
      care received were 19.0% (118/620). The distribution of the cause of the injury
      based on accordance with the lex artis showed significant differences.
      CONCLUSIONS: In our country, the number of claims for claimed medical liability
      is increasing, predominantly in relation to surgical specialties, where a medical
      act is more likely to be considered not in accordance with the lex artis. In
      addition, in a significant percentage of cases, no conclusions are drawn about
      the medical act.

PMID- 24100816
TI  - [Sexually transmitted infections in women living in a prison in Lima, Peru].
AB  - In order to determine the prevalence of sexually transmitted infections (STI) in
      recluse women of Chorrillos Penitentiary I in the city of Lima, Peru, a cross
      sectional study was performed, including a simple random sample of women between
      ages 18 and 54, from whom 180 serum samples and 168 samples of cervical and
      vaginal discharge were analyzed. The most prevalent etiologic agents identified
      from cervical and vaginal discharge samples were Chlamydia trachomatis in 42.3%,
      Gardnerella vaginalis in 24.4% and Trichomonas vaginalis in 10.1% and for serum
      samples the most prevalent were syphilis and HIV, both in 2.2%. We conclude that
      there is a high prevalence of sexually transmitted infections in recluse women of
      Chorrillos Penitentiary I in the city of Lima, Peru. There should be routine
      screenings established for diagnosis and treatment of STIs within the prison
      system and this population should be included in the sexual and reproductive
      health programs. 

PMID- 24100815
TI  - [Surgical treatment for left-sided heart valve disease in a national reference
      hospital in Lima, Peru].
AB  - OBJECTIVES: To describe the preoperative, intraoperative and postoperative
      characteristics of patients with left-sided heart valve disease treated in the
      thoracic and cardiovascular surgery service of a national reference hospital; as
      well as to describe the occurrence of thromboembolic and bleeding events in these
      patients. MATERIALS AND METHODS: A retrospective longitudinal study was carried
      out, which included 185 patients who underwert surgery between 1999 and 2006 at
      the Hospital Nacional Dos de Mayo (Lima, Peru). The patients were divided into 4
      groups: patients with mitral commissurotomy; with aortic valve replacement; with
      mitral valve replacement and with double valve replacement. T-student test, Chi
      square test, analysis of variance and Bonferroni test were used. The survival
      analysis took into account the severe thromboembolic and bleeding events and a
      follow-up period of 7 years was set. RESULTS: The average durations of disease
      was 4.6 years. The most frequent etiology was rheumatic valve disease (74.6%).
      Hospital mortality was 3.8%, the most frequent cause of death was low cardiac
      output syndrome associated to multiple organ failure. The incidence of ischemic
      events (thrombosis or embolization) in patients who had a long-term valve
      replacement (more than 6 months) was 3.2%, and the incidence of bleeding events
      was 4.3%. CONCLUSIONS: The results of surgical treatment for left-sided heart
      valve disease in Peru are favorable. The rate of complications and hospital
      mortality rate, as well as the long-term thromboembolic and bleeding events are
      comparable to those reported in the world literature.

PMID- 24100817
TI  - [Impact of the application of the American Thyroid Association criteria on the
      diagnosis of hypothyroidism in pregnant women in Vigo, Spain].
AB  - In order to determine the impact of the application of the American Thyrold
      Associations (ATA) criteria for the diagnosis of hypothyroidism in pregnant women
      in the health district of Vigo, Spain, concentrations of serum thyrotropin (TSH),
      free thyroxine (T4L) and anti-thyroid antibodies were analyzed, comparing the
      frequency of pregnant women diagnosed with hypothyroidism and applying the
      criteria used in the hormone laboratory at Xeral Hospital and referential
      criteria established by ATA. The application of ATA referential criteria
      increased by 29.6% the number of female patients diagnosed with hypothyroidism.
      The application of ATA guidelines had an impact on the measurement of TSH
      concentrations in pregnant women, which calls for an evaluation of referential
      values of TSH based on the population and the local diagnostic methods. 

PMID- 24100818
TI  - [Clinical characteristics and geriatric evaluation of elderly patients with
      pneumonia in a hospital in Buenos Aires, Argentina].
AB  - In order to determine the clinical and geriatric characteristics of elderly
      adults with pneumonia in a hospital in Buenos Aires, Argentina, a cross-sectional
      study was carried out in 2010, included 66 patients hospitalized for pneumonia.
      The mean age of the study subjects was 82, 54.5% of whom were men. 47.0% of the
      hospitalizations were due to community-acquired pneumonia. As for the functional
      evaluation, 31.8% showed dependence in performing basic activities of daily
      living and 69.4% presented dependence in instrumental activities of daily living.
      The most frequent clinical characteristics observed were fever, cough, dyspnea
      and expectoration. The causative agent of pneumonia was identified in 34.8% of
      the cases, 18 of which were bacterial (27.2%) and 5 viral (7.5%). The crude
      mortality rate was 28.8%, but was close to 50% in those patients having
      confusional syndrome. We conclude that pneumonia in elderly patients has special
      characteristics, which can be observed with a proper diagnostic and geriatric
      evaluation. 

PMID- 24100819
TI  - [Eccrine Porocarcinoma: clinical-pathological study of 19 cases in the Instituto
      Nacional de Enfermedades Neoplasicas, Lima - Peru].
AB  - In order to describe the clinical-pathological characteristics of the cases of
      Eccrine Porocarcinoma (EP) found in the Instituto Nacional de Enfermedades
      Neoplasicas (INEN), a cross-sectional study was carried out, including all EP
      cases recorded between 1998 and 2009. A revision of the clinical-pathological
      records indentified and a new reading of the pathology slides of the cases found
      were performed. 19 EP cases were found, the median age of which was 64 years
      (range: 37-98). EP was primarily found on male patients (57.9%) and was most
      commonly located on the foot (21.1%), followed by the head, thorax and thigh
      (15.8%, respectively). In one case, EP was located on the gluteal region, and
      showed an unusually invasive behavior and rectal involvement. We conclude that EP
      is a rather uncommon entity in Peru. Its most common location is on the foot and
      it affects mostly male patients for the most part. 

PMID- 24100820
TI  - [In silico identification of molecular mimicry between T-cell epitopes of
      Neisseria meningitidis B and the human proteome].
AB  - The objective of the study was to determine the T-cell epitopes of four of the
      most frequent antigenic proteins of the outer membrane of Neisseria meningitidis
      B, and to identify the most relevant sites for molecular mimicry with T-cell
      epitopes in humans. In order to do so, an in silico study -a type of study that
      uses bioinformatic tools- was carried out using SWISS-PROT/TrEMBL, SYFPEITHI and
      FASTA databases, which helped to determine the protein sequences, CD4 and CD8 T
      cell epitope prediction, as well as the molecular mimicry with humans,
      respectively. Molecular similarity was found in several human proteins present in
      different organs and tissues such as: liver, skin and epithelial tissues, brain,
      lymphatic system and testicles. Of these, those found in testicles were more
      similar, showing the highest frequency of mimetic sequences. This finding shed
      light on the success of N. meningitidis B to colonize human tissues and the
      failure of certain vaccines against this bacterium, and it even helps to explain
      possible autoimmune reactions associated with the infection or vaccination. 

PMID- 24100821
TI  - [Cathepsin L cysteine protease from Taenia solium: its biological role in the
      infection and potential use for the immunodiagnosis of neurocysticercosis].
AB  - Taenia solium is a plane helminth responsible for taeniasis and human
      cysticercosis, the latter being the result of the consumption of infective eggs.
      Cysticerci can develop in different human tissues, often in the central nervous
      system, causing neurocysticercosis (NCC). For the diagnosis of NCC, an adequate
      interpretation of clinical data, neuroimaging results and serological tests are
      required. However, serological tests could be improved by developing candidate
      antigens able to increase their sensibility and specificity. In the last years, a
      series of surface and secretory proteins of T. solium essential for the parasite
      host interaction have been described. One of these families is cathepsin L
      cysteine proteases, which have a predominant role in the development and survival
      of the parasite. They take part in the tissue invasion, immune response evasion,
      excystation and encystment of cysticercus. They are considered potential antigens
      for the immunodiagnosis of neurocysticercosis. 

PMID- 24100822
TI  - [The Cairo Conference and the assertion of sexual and reproductive rights as a
      basis for sexual and reproductive health].
AB  - The article focuses on the International Conference on Population and Development
      held in El Cairo, Egypt, in 1994. The Conference addressed issues related to
      sexual and reproductive rights, actions to be adopted to improve the situation of
      young girls, the status of women, the situation of adolescents and gender
      equality as basic components to improve the sexual and reproductive health of the
      population. The concluding recommendations in this conference constitute the
      action program. This document also addresses some issues that generated long
      discussions to reach consensus during the conference. It summarizes the follow up
      performed on the action program in the following years and ends with the report
      of the Peruvian government and the civil society twenty years after the
      conference. 

PMID- 24100823
TI  - [Situation of maternal mortality in Peru, 2000 - 2012].
AB  - We perform an analysis concerning the situation of maternal mortality in Peru,
      based on the information of the System of Epidemiologic Surveillance of Maternal
      Mortality of the General Directorate of Epidemiology of the Ministry of Health
      and the Family and Health Demographic Survey. We can see a decrease in the rates
      of maternal mortality between 2000 and 2012. The direct causes are the same but
      in different proportions according to the natural regions, being the hemorrhage
      the first cause of maternal mortality. The coverage of birth attention in health
      establishments has increased in the last years but it is still necessary to
      improve the capacity of quick response and the quality of the health services.
      Maternal mortality in Peru is related to inequity and lack of women empowerment
      to excerpt their rights, specially the sexual and reproductive rights. It is
      necessary to strengthen the strategies that have been implemented in order to
      accomplish of the reduction in maternal mortality in Peru. 

PMID- 24100824
TI  - [Family planning as a basic tool for development].
AB  - The family planning (FP) concept has traditionally been, and is closely related
      to, sexual and reproductive health. At the International Conference on Population
      and Development held in Cairo in 1994, FP is recognized as a health strategy
      that, properly applied, can contribute to the development of nations. Over the
      past years we have found that the benefits are not only aimed at preventing
      unwanted pregnancies, there by preventing induced abortions and maternal death,
      but it also improves child health, facilitating access to education for children
      in the world, it promotes the empowerment of women not only in the workplace but
      also in other areas such as politics and thus, the concept of gender; it helps to
      reduce poverty by stimulating economic development and increasing the standard of
      living of people . This means that it not only contributes to one but to the
      eight Millennium Development Goals by 2015. Despite the evidence of its benefits,
      there are still social, cultural, political or religious barriers that cause an
      unmet need in Family Planning, which does not respect the right of individuals to
      choose and decide the number of children they want, and prevent the experience of
      a healthy sexuality. 

PMID- 24100825
TI  - [Adolescent pregnancy in Peru: its current situation and implications for public
      policies].
AB  - This article ellaborates on the relation between peruvian pregnant adolescents of
      15 to 19 years of age and poverty, malnutrition and social exclusion, proposing
      alternatives for their medical care within the frame of social programs and the
      fight against poverty. Likewise, it describes and analyzes the trends recorded
      over the past 20 years, emphasizing the multiple and persistent inequalities.
      Over this period, prevalences have not changed substantially, despite a slight
      drop recorded in the rural area. First, the article analyzes these trends in the
      light of their closest determinants, including changes in teenagers'exposure to
      the risk of an unplanned pregnancy. Then, it describes the impact this situation
      has on adolescents and their children, as well as the economic and labour
      impacts. Finally, it examines the experiences of countries with social programs
      similar to the one in Peru, highlighting those which could be implemented in our
      country.

PMID- 24100826
TI  - [Role of men in contraception, as users and partners].
AB  - Reproductive health programs have focused their attention on women; in general,
      they have not worked much with men. Gender is not only a determinant of
      inequality, but it also provides explanations for the different factors that have
      an impact on men and women's health, their disease and their death. This article
      addresses the factors that are prioritized over the information and decisions
      concerning the exercise of sexuality and how to regulate reproduction. With
      regards to the beginning of sexual life, men seem to start earlier, in average,
      they have their first sexual relation at 16.8 years old. As to the use of
      contraceptive methods, currently 54.2% of men declare to use them. Out of these,
      39.5% choose modern methods whereas 14.5% prefer traditional ones. In Peru, among
      the modern methods available are the barrier methods (the condom being the most
      used), the chemical methods or spermicides, and the surgical methods (vasectomy).
      Among the traditional ones are the "rhythm" based on abstinence during the
      fertile phase of the menstrual cycle, and the coitus interruptus. The father's
      role is one of power. Gender relations are relations of power, and parenthood is
      part of these relations. The father is, above all, the provider of filiation.
      Marginalization of men in the reproductive process is evident. Their support to
      their partner is suboptimal, whether it is during pregnancy, during delivery or
      to prevent the death of the mother.

PMID- 24100827
TI  - [Emergency oral contraception policy: the Peruvian experience].
AB  - Emergency oral contraception is part of the sexual and reproductive rights of
      women. In 2001, this health policy was incorporated into the Rules of the
      National Family Planning Program of the Ministry of Health, primarily to prevent
      unwanted pregnancy and its serious consequences, induced abortion and the high
      associated maternal mortality rate, which are major public health problems.
      Scientific research has confirmed that the main mechanism of action of
      levonorgestrel, component of emergency oral contraception (EOC) is to inhibit or
      delay ovulation, preventing fertilization of the egg; additionally, it increases
      the thickening of the cervical mucus, making the sperm migration more difficult.
      No study has found endometrial abnormalities that may interfere with the
      implantation of the fertilized egg or embryo development of an implanted egg.
      However, despite the support of medical science and legal backing, the EOC is
      available only to users with economic resources, but its use has not been fully
      implemented in public sector services, due to obstacles created by groups opposed
      to contraception under claim of an alleged abortive effect that has already been
      ruled out scientifically. This article describes the administrative experience
      and legal confrontations between groups of power that prevent the proper
      implementation of an emergency contraception policy in Peru. 

PMID- 24100828
TI  - [Therapeutic abortion, unjustified absence in health policy].
AB  - Although abortion for health reasons is not considered a crime in Peru, the State
      does not allow its inclusion in public policy, thus violating women's right to
      terminate a pregnancy when it affects their health. When examining the article in
      the Criminal Code which decriminalizes this type of abortion, provisions are
      identified which protect women and set the conditions to offer this type of
      service. This document sets the debate about the arguments used by the Peruvian
      State for not approving a therapeutic abortion protocol which would regulate the
      provision and financing of therapeutic abortion in public services, and explains
      why this obligation should be complied with, based on the conceptual framework of
      "health exception" In addition, it presents two cases brought before the judicial
      court in which the Peruvian State was found guilty of violating the human rights
      of two adolescents to whom a therapeutic abortion was denied.

PMID- 24100829
TI  - [The criminalization of sexual relations between or with adolescents and its
      impact on the exercise of their sexual and reproductive rights].
AB  - This article analyzes the impact of the decrete 28704, issued in 2006, on the
      Peruvian society. This Law states that all sexual relations between the age of 14
      and an age younger than 18, whether consented or not, shall be considered rape,
      thus criminalizing adolescent sexuality and making preventive reproductive health
      services illegal. This decision was made disregarding the legal frameworks which
      recognize and protect sexual and reproductive rights, the needs of adolescents
      regarding sexuality, as well as its impact on public health issues. In 2012, this
      Law was declared unconstitutional. The enforcement of this sentence shall enable
      the implementation and improvement of public sexual education policies and the
      access to quality health care. An effort to create more effective laws to protect
      adolescents from sexual violence must be made. 

PMID- 24100830
TI  - [Report of four clinical cases of filariasis in Alto Nanay, Loreto].
AB  - This study describes the clinical, parasitological and laboratory findings of
      four patients who lived in the district of Alto Nanay, Maynas, Loreto, Peru and
      were infected with Mansonella ozzardi microfilariae. Clinical examinations by
      ophthalmologists, cardiologists and nephrologists were performed. In case 1, the
      presence of 2 subcutaneous lumps was the most important finding, one at dorsal
      level and the other in the lower third of the left leg; in case 2, there was a
      sensation of tingling or coldness in the legs; in case 3, an associated chronic
      hepatitis B infection was found, and in case 4, a large lump was detected in the
      left lumbar region. All 4 patients were infected with Mansonella ozzardi and had
      eosinophilia, 3 of them in percentages of 20%. The lump found in case 4 was due
      to a herniation of bowel content. Further clinical studies and an evaluation of
      the actual pathogenic effect of microfilariae are to be performed. A study of the
      genetic diversity of filariae in the Peruvian Amazon would also be important. 

PMID- 24100831
TI  - [Institutional iatrogeny and maternal death: Semmelweis and puerperal fever].
AB  - Puerperal fever is a disease that becomes epidemic in the eighteenth century as a
      result of two factors: the urban working masses generated by the industrial
      revolution and the progressive hegemonization and medicalization of birth care in
      large public hospitals. Institutionalized maternal death reached figures above
      30%, while in the case of birth care provided by midwives, it was than 2%.
      Semmelweis, an Hungarian physician, sustained that physicians contaminated women
      in labor due to insufficient hygiene after performing necropsies and established
      prophylactic measures in the Vienna Hospital that reduced mortality dramatically.
      However, his ideas were rejected because they affected the institutionalization
      process of medicine, based on altruism and honor, which would make it impossible
      to cause harm to patients. He was forced to leave Vienna Hospital and he
      continued his struggle in Budapest, but the rejection and disagreement of his
      peers with his doctrine affected his mental health. He died in an asylum, a few
      years before Pasteur and Koch proved the existence of the bacteria that caused
      diseases such as puerperal fever. 

PMID- 24100832
TI  - [Sexual representation in pre Columbian Moche ceramics, Peru].

PMID- 24100833
TI  - [Forced sterilizations, reproductive rights and informed consent].

PMID- 24100834
TI  - [Application of an electronic information system to the cervical cancer screening
      program].

PMID- 24100835
TI  - [Interventions of the maternal and newborn health program based on financing for
      performance].

PMID- 24100836
TI  - [Cognitive functions of HIV/AIDS positive individuals attending a comprehensive
      care program].

PMID- 24100837
TI  - [CTX-M-type extended-spectrum beta-lactamase in Shigella flexneri isolates from
      pediatric patients with acute diarrhea].

PMID- 24100838
TI  - [Information systems for dengue about Peru: need for real-time monitoring and
      analysis].

PMID- 24100839
TI  - [Complementary occupational risk insurance for health care personnel].

PMID- 24100840
TI  - Nano-antenna in a photoconductive photomixer for highly efficient continuous wave
      terahertz emission.
AB  - We report highly efficient continuous-wave terahertz (THz) photoconductive
      antenna based photomixer employing nano-gap electrodes in the active region. The
      tip-to-tip nano-gap electrode structure provides strong THz field enhancement and
      acts as a nano-antenna to radiate the THz wave generated in the active region of
      the photomixer. In addition, it provides good impedance matching to the THz
      planar antenna and exhibits a lower RC time constant, allowing more efficient
      radiation especially at the higher part of the THz spectrum. As a result, the
      output intensity of the photomixer with the new nano-gap electrode structure in
      the active region is two orders of magnitude higher than that of a photomixer
      with typical interdigitated electrodes. Significant improvement in the THz
      emission bandwidth was also observed. An efficient continuous wave THz source
      will greatly benefit compact THz system development for high resolution THz
      spectroscopy and imaging applications. 

PMID- 24100843
TI  - Screening for BK viremia.

PMID- 24100845
TI  - Renal postconditioning...pause for thought? Correspondence regarding "Protection
      against renal ischemia-reperfusion injury by ischemic postconditioning".

PMID- 24100844
TI  - Screening for BK viremia reduces but does not eliminate the risk of BK
      nephropathy.

PMID- 24100846
TI  - Response to "Renal postconditioning...pause for thought?".

PMID- 24100847
TI  - International kidney paired donation.

PMID- 24100848
TI  - Splenic large B-cell lymphoma 17 years after exposure to aristolochic acid.

PMID- 24100849
TI  - A cyanobenzo[a]phenoxazine-based near infrared lysosome-tracker for in cellulo
      imaging.
AB  - A cyanobenzo[a]phenoxazine-based pH probe with pKa = 5.0 exhibits OFF-ON emission
      at 625-850 nm upon excitation at 600 nm in aqueous buffers. The in cellulo
      imaging experiments with HeLa cells indicate that the probe can serve as a
      lysosome-specific probe under red light excitation (633 nm) with near infrared
      emission (650-790 nm). 

PMID- 24100850
TI  - Doubts raised over political support for hospital reconfiguration.

PMID- 24100851
TI  - Draft EU research programme doesn't deal with disease risk factors, say public
      health doctors.

PMID- 24100852
TI  - Insurance payments to US doctors vary widely for same service, study shows.

PMID- 24100853
TI  - Polio is re-emerging in areas previously considered polio free.

PMID- 24100854
TI  - Suspension of GP over treatment of drug misuser is extended for 12 months.

PMID- 24100855
TI  - Improving employee productivity through improved health.
AB  - OBJECTIVE: The objective of this study was to estimate productivity-related
      savings associated with employee participation in health promotion programs.
      METHODS: Propensity score weighting and multiple regression techniques were used
      to estimate savings. These techniques were adjusted for demographic and health
      status differences between participants who engaged in one or more telephonic
      health management programs and nonparticipants who were eligible for but did not
      engage in these programs. RESULTS: Employees who participated in a program and
      successfully improved their health care or lifestyle showed significant
      improvements in lost work time. These employees saved an average of $353 per
      person per year. This reflects about 10.3 hours in additional productive time
      annually, compared with similar, but nonparticipating employees. CONCLUSIONS:
      Participating in health promotion programs can help improve productivity levels
      among employees and save money for their employers.

PMID- 24100858
TI  - Preliminary results of antiscarring therapy in the prevention of postendoscopic
      esophageal mucosectomy strictures.
AB  - BACKGROUND: Esophageal endoscopic submucosal dissection (ESD) is an effective
      minimally invasive therapy for early esophageal cancer and high-grade Barrett
      dysplasia. However, esophageal stricture formation after circumferential or large
      ESD has limited its wide adoption. Mitomycin C (MMC), halofuginone (Hal), and
      transforming growth factor beta3 (TGF-beta3) exhibits antiscarring effects that
      may prevent post-ESD stricture formation. METHODS: Using endoscopic mucosectomy
      (EEM) technique, an 8- to 10-cm-long circumferential esophageal mucosal segment
      was excised in a porcine model. The site was either untreated (control, n = 6) or
      received 40 evenly distributed injections of antiscarring agent immediately and
      at weeks 1 and 2. High and low doses were used: MMC 5 mg (n = 2), 0.5 mg (n = 2);
      Hal 5 mg (n = 2), 1.5 mg (n = 2), 0.5 mg (n = 2); TGF-beta3 2 MUg (n = 2), 0.5
      MUg (n = 2). The degree of stricture formation was determined by the percentage
      reduction of the esophageal lumen on weekly fluoroscopic examination. Animals
      were euthanized when strictures exceeded 80 % or the animals were unable to
      maintain weight. RESULTS: The control group had a luminal diameter reduction of
      78.2 +/- 10.9 % by 2 weeks and were euthanized by week 3. Compared at 2 weeks,
      the Hal group showed a decrease in mean stricture formation (68.4 % low dose,
      57.7 % high dose), while both TGF-beta3 dosage groups showed no significant
      change (65.3 % low dose, 76.2 % high dose). MMC was most effective in stricture
      prevention (53.6 % low dose, 35 % high dose). Of concern, the esophageal wall
      treated with high-dose MMC appeared to be necrotic and eventually led to
      perforation. In contrast, low dose MMC, TGF-beta3 and Hal treated areas appeared
      re-epithelialized and healthy. CONCLUSIONS: Preliminary data on MMC and Hal
      demonstrated promise in reducing esophageal stricture formation after EEM. More
      animal data are needed to perform adequate statistical analysis in order to
      determine overall efficacy of antiscarring therapy.

PMID- 24100859
TI  - Fundamentals of Endoscopic Surgery cognitive examination: development and
      validity evidence.
AB  - BACKGROUND: Flexible endoscopy is an integral part of surgical care. Exposure to
      endoscopic procedures varies greatly in surgical training. The Society of
      American Gastrointestinal and Endoscopic Surgeons has developed the Fundamentals
      of Endoscopic Surgery (FES), which serves to teach and assess the fundamental
      knowledge and skills required to practice flexible endoscopy of the
      gastrointestinal tract. This report describes the validity evidence in the
      development of the FES cognitive examination. METHODS: Core areas in the practice
      of gastrointestinal endoscopy were identified through facilitated expert focus
      groups to establish validity evidence for the test content. Test items then were
      developed based on the content areas. Prospective enrollment of participants at
      various levels of training and experience was used for beta testing. Two FES
      cognitive test versions then were developed based on beta testing data. The
      Angoff and contrasting group methods were used to determine the passing score.
      Validity evidence was established through correlation of experience level with
      examination score. RESULTS: A total of 220 test items were developed in
      accordance with the defined test blueprint and formulated into two versions of
      120 questions each. The versions were administered randomly to 363 participants.
      The correlation between test scores and training level was high (r = 0.69), with
      similar results noted for contrasting groups based on endoscopic rotation and
      endoscopic procedural experience. Items then were selected for two test forms of
      75 items each, and a passing score was established. CONCLUSIONS: The FES
      cognitive examination is the first test with validity evidence to assess the
      basic knowledge needed to perform flexible endoscopy. Combined with the hands-on
      skills examination, this assessment tool is a key component for FES
      certification.

PMID- 24100861
TI  - Construct validity of nine new inanimate exercises for robotic surgeon training
      using a standardized setup.
AB  - BACKGROUND: As more surgeons choose to complete procedures robotically, validated
      training tools are needed so that they can acquire and maintain the technical
      skills required to proficiently use robotic systems. The purpose of this study
      was to show construct validity of nine new inanimate training exercises for robot
      assisted surgery. The inanimate training exercises were designed to span several
      core technical skills required to use a robotic system. METHODS: New (n = 30) and
      experienced (n = 11) robotic surgeons participated in the study. New robotic
      surgeons had not yet completed their first robotic surgery case and participated
      in this study before attending their robotic certification course. Experienced
      robotic surgeons had completed more than 200 robotic surgery cases. The raw
      scores from the exercises were reported so that other research groups could
      easily define custom proficiency levels. Example normalized scores that could be
      used in proficiency-based curricula were computed. These normalized scores
      balanced efficiency (completion time) and accuracy (exercise-specific errors) to
      measure performance. Finally, the setup was standardized using a custom docking
      model, which enabled consistent and repeatable completion of the inanimate
      exercises across surgeons. RESULTS: For all nine exercises, experienced robotic
      surgeons completed the exercises significantly faster than new robotic surgeons
      (p < 0.01). Similarly, experienced robotic surgeons achieved higher normalized
      scores than new robotic surgeons for all nine exercises (p < 0.01). Finally,
      consistent robot setup was achieved using the custom docking model based on an
      analysis of the robot kinematic data. CONCLUSIONS: In summary, all nine inanimate
      exercises showed construct validity. The results suggest that the inanimate
      exercises along with the custom docking model can be used as part of proficiency
      based curricula to improve robotic surgeon training.

PMID- 24100862
TI  - Outcomes following laparoscopic transhiatal esophagectomy for esophageal cancer.
AB  - BACKGROUND: Most published minimally invasive esophagectomy techniques involve a
      multiple field approach, including laparoscopic and thoracoscopic esophageal
      mobilization. Laparoscopic transhiatal esophagectomy (LTE) should potentially
      reduce the complications associated with thoracotomy. This study aims to compare
      outcomes of LTE with open transhiatal esophagectomy (OTE) and en-bloc
      esophagectomy (EBE). METHODS: Retrospective chart review was performed on all
      patients who had an LTE for cancer between July 2008 and July 2012 at our
      institution. Data was compared with an historic cohort of patients who underwent
      OTE and EBE at the same institution from July 2002 to July 2008. RESULTS: There
      were 33 patients with LTE, compared with 60 patients with OTE and 139 with EBE.
      The presence of minor operative complications was similar (p = 0.36), but major
      complications were significantly less common in the LTE group (12, 23 and 33 %,
      respectively; p = 0.04). The median number of blood transfusions during
      hospitalization was significantly lower in the LTE group (0, 2.5 and 3,
      respectively; p = 0.005). Median tumor size was significantly smaller (1.5, 2.2,
      and 3 cm, respectively; p = 0.03), but the LTE group had a significantly higher
      percentage of patients with neoadjuvant treatment (39, 14 and 29 %, respectively;
      p = 0.008). Median lymph node yield for LTE was lower (24, 36 and 48,
      respectively; p < 0.0001), but the percentage of patients with positive nodes was
      similar (33, 33 and 39 %, respectively; p = 0.69). Mortality was equivalent among
      the groups (0, 2 and 4 %, respectively; p = 0.38). The median LOS for the LTE
      group was significantly lower (10, 13 and 15 days, respectively; p < 0.0001).
      Overall survival was not different between the three groups (p = 0.65), with
      median survival at 24 months of 70, 65 and 65 %, respectively. CONCLUSION: LTE
      can be performed safely with less major complications and shorter hospital stay
      than open esophagectomy. The reduced lymph-node harvest did not impact overall
      survival.

PMID- 24100865
TI  - Regulation of YAP through an Akt-dependent process by 3, 3'-diindolylmethane in
      human colon cancer cells.
AB  - Cancer development is a complex process governed by the interaction of several
      signaling pathways. The Hippo and PI3K/Akt pathways have been shown to play a
      critical role in controlling tissue growth involved in the regulation of cell
      proliferation. 3, 3'-diindolylmethane (DIM) is a natural compound that
      selectively kills cancer cells without causing toxicity to normal cells. This
      study aims to investigate whether DIM has an effect on the Hippo signaling
      pathway mediated via the PI3K/Akt signaling pathway in colon cancer cells. Our
      study provides new insights into the mechanisms of crosstalk between Hippo
      signaling and the Akt pathway controlling cell proliferation by PI3K inhibitor
      and DIM treatment in colon cancer cells. DIM strongly potentiates the lethality
      of LY294002 in HCT116 cells and inhibits proliferation of colon cancer cells via
      inactivation of Akt and YAP. Thus, DIM has dramatic therapeutic effects when it
      is combined with the PI3K inhibitor in the treatment of colon cancer cells. These
      findings highlight the potential usefulness of DIM and can help develop
      therapeutic strategies for the prevention and treatment of colon cancer. 

PMID- 24100866
TI  - A new study on the energy transfer in the color-tunable phosphor CaWO4:Bi.
AB  - In this article, the scheelite-structured phosphors of CaWO4 and Bi(3+) doped
      CaWO4 were successfully synthesized by the high temperature solid state reaction,
      and the photoluminescence (PL) properties and decay curves of the samples were
      investigated between 10 and 300 K. The results have shown clearly that the sample
      emission is tunable via tailoring the energy transfer between the Bi(3+) and
      WO4(2-) anion groups by the selection of either proper bismuth content or
      excitation scheme. Depending on the excitation scheme, energy transfer does
      happen from Bi(3+) to WO4(2-) or in the reverse, which, however, has never been
      noticed. Direct spectroscopic evidences as well as the mechanism have been
      presented for these processes in this work. 

PMID- 24100864
TI  - Association of white matter deficits with clinical symptoms in antipsychotic
      naive first-episode schizophrenia: an optimized VBM study using 3T.
AB  - OBJECT: To examine the whole brain white matter morphology in antipsychotic-naive
      patients with first-episode schizophrenia (FES) and its correlations with symptom
      severity. MATERIALS AND METHODS: High-resolution T1-weighted images of 64 drug
      naive FES patients and 64 matched healthy controls were acquired using a 3 T MR
      imaging system. Then, optimized voxel-based morphometry was performed to compare
      the group differences. Finally, correlation analyses were conducted between the
      white matter volume (WMV) changes and clinical symptoms. RESULTS: The FES showed
      significantly decreased WMV in the bilateral posterior limb of the internal
      capsule (PLIC) and right subgyral frontal white matter. The volume of the
      bilateral PLIC was negatively correlated with the Positive and Negative Syndrome
      Scale positive scores. Positive correlations were observed between all of the
      changed WMV measures and the Global Assessment of Functioning scores. CONCLUSION:
      The current findings provide further evidence to support internal capsule and
      subgyral frontal white matter deficits at the early stage of schizophrenia that
      are potentially related to the core pathophysiology of the disease. Furthermore,
      these anatomical alterations were related to the clinical symptoms but not the
      untreated illness duration, suggesting that these deficits are related to
      aberrations in the neurodevelopmental process and may be relatively stable during
      the early course of schizophrenia.

PMID- 24100867
TI  - COX10 mutations resulting in complex multisystem mitochondrial disease that
      remains stable into adulthood.
AB  - IMPORTANCE: Isolated cytochrome-c oxidase (COX) deficiency is one of the most
      frequent respiratory chain defects seen in human mitochondrial disease.
      Typically, patients present with severe neonatal multisystem disease and have an
      early fatal outcome. We describe an adult patient with isolated COX deficiency
      associated with a relatively mild clinical phenotype comprising myopathy;
      demyelinating neuropathy; premature ovarian failure; short stature; hearing loss;
      pigmentary maculopathy; and renal tubular dysfunction. OBSERVATIONS: Whole-exome
      sequencing detected 1 known pathogenic and 1 novel COX10 mutation: c.1007A>T;
      p.Asp336Val, previously associated with fatal infantile COX deficiency, and
      c.1015C>T; p.Arg339Trp. Muscle COX holoenzyme and subassemblies were undetectable
      on immunoblots of blue-native gels, whereas denaturing gels and
      immunocytochemistry showed reduced core subunit MTCO1. Heme absorption spectra
      revealed low heme aa3 compatible with heme A:farnesyltransferase deficiency due
      to COX10 dysfunction. Both mutations demonstrated respiratory deficiency in
      yeast, confirming pathogenicity. A COX10 protein model was used to predict the
      structural consequences of the novel Arg339Trp and all previously reported
      substitutions. CONCLUSIONS AND RELEVANCE: These findings establish that COX10
      mutations cause adult mitochondrial disease. Nuclear modifiers, epigenetic
      phenomenon, and/or environmental factors may influence the disease phenotype
      caused by reduced COX activity and contribute to the variable clinical severity
      related to COX10 dysfunction.

PMID- 24100868
TI  - Targeted delivery of colloids by swimming bacteria.
AB  - The possibility of exploiting motile microorganisms as tiny propellers represents
      a fascinating strategy for the transport of colloidal cargoes. However, delivery
      on target sites usually requires external control fields to steer propellers and
      trigger cargo release. The need for a constant feedback mechanism prevents the
      design of compact devices where biopropellers could perform their tasks
      autonomously. Here we show that properly designed three-dimensional (3D)
      microstructures can define accumulation areas where bacteria spontaneously and
      efficiently store colloidal beads. The process is stochastic in nature and
      results from the rectifying action of an asymmetric energy landscape over the
      fluctuating forces arising from collisions with swimming bacteria. As a result,
      the concentration of colloids over target areas can be strongly increased or
      depleted according to the topography of the underlying structures. Besides the
      significance to technological applications, our experiments pose some important
      questions regarding the structure of stationary probability distributions in non
      equilibrium systems. 

PMID- 24100869
TI  - Ultrathin nanostructured metals for highly transmissive plasmonic subtractive
      color filters.
AB  - Plasmonic color filters employing a single optically-thick nanostructured metal
      layer have recently generated considerable interest as an alternative to colorant
      based color filtering technologies, due to their reliability, ease of
      fabrication, and high color tunability. However, their relatively low
      transmission efficiency (~30%) needs to be significantly improved for practical
      applications. The present work reports, for the first time, a novel plasmonic
      subtractive color filtering scheme that exploits the counter-intuitive phenomenon
      of extraordinary low transmission (ELT) through an ultrathin nanostructured metal
      film. This approach relies on a fundamentally different color filtering mechanism
      than that of existing plasmonic additive color filters, and achieves unusually
      high transmission efficiencies of 60 ~ 70% for simple architectures. Furthermore,
      owing to short-range interactions of surface plasmon polaritons at ELT
      resonances, our design offers high spatial resolution color filtering with
      compact pixel size close to the optical diffraction limit (~lambda/2), creating
      solid applications ranging from imaging sensors to color displays. 

PMID- 24100870
TI  - Molecular and clinical characteristics of MSH6 germline variants detected in
      colorectal cancer patients.
AB  - The MSH6 gene is one of the mismatch repair genes involved in Lynch syndrome and
      its mutations account for 10-20% of Lynch syndrome. Although previous studies
      suggested that the difference of the geographical region affects the clinical
      phenotype of Lynch syndrome, there has been no report on the detailed features of
      Japanese Lynch syndrome patients carrying an MSH6 mutation. The aim of the
      present study was to investigate the clinical and molecular features of MSH6
      mutation carriers in Japan. Surgically resected 1720 colorectal carcinoma
      specimens were screened by microsatellite instability (MSI) testing and the MSI
      high cases were subjected to a germline mutation analysis of the mismatch repair
      genes MLH1, MSH2 and MSH6. We investigated the clinical and molecular features of
      the MSH6 variants, such as the family cancer history, pathological findings,
      immunohistochemistry, methylation status of the MLH1 promoter and BRAF mutation
      in the colorectal tumor. Furthermore, the impact of the missense variants on MSH6
      protein was predicted by using in silico tools. We identified nine novel
      pathogenic mutations and eight unclassified missense variants. Among the eight
      missense variants, three were suspected pathogenic by in silico analysis. We also
      found that most colorectal cancers in the MSH6 mutation carrier were diagnosed
      after the age of 50 and were localized distally. Furthermore, the mean age at
      diagnosis of endometrial cancer in Japanese MSH6 mutation carriers (49.2 years)
      was earlier than previous reports from Western countries (56.5 years). These
      results may improve the surveillance program for Japanese MSH6 mutation carriers.

PMID- 24100871
TI  - Optimization and simplification of antiretroviral therapy for adults and
      children.
AB  - PURPOSE OF REVIEW: The review reflects on opportunities and challenges for HIV
      treatment optimization for the next 5 years. RECENT FINDINGS: Considering all
      currently available options, the fixed-dose combination of tenofovir + lamivudine
      (or emtricitabine) + efavirenz is considered as the best option for first-line
      treatment for the short to medium term. Second-line therapy will likely continue
      to be comprised of a boosted protease inhibitor in combination with two
      nucleoside/nucleotide reverse transcriptase inhibitors (NRTIs), with potential
      for combining with integrase inhibitors. For children, there is potential for
      simplification and harmonization with adult antiretroviral regimens. First-line
      therapy for children younger than 3 years of age may be best delivered using two
      nucleoside reverse transcriptase inhibitors (NRTIs) and a boosted protease
      inhibitor; above 3 years of age, the standard of care is two NRTIs and a non
      nucleoside reverse transcriptase inhibitor (NNRTI) as recommended for adults.
      Important research questions include the dosing and safety of new antiretroviral
      agents and formulations, particularly once-daily fixed-dose combinations, the
      role of integrase inhibitors and the optimal second-line regimen for NNRTI
      exposed children who fail protease inhibitor-containing first-line regimens.
      SUMMARY: Treatment simplification is critical to further antiretroviral therapy
      scaling-up and support long-term retention in care. Future guidance should
      consider the broader benefits of earlier antiretroviral therapy initiation beyond
      potential AIDS mortality reduction, notably mitigation of short- and long-term
      HIV-associated comorbidities, reduction of HIV transmission, increased retention
      in care, and enhancing programme simplification.

PMID- 24100872
TI  - Beyond first-line HIV treatment regimens: the current state of antiretroviral
      regimens, viral load monitoring, and resistance testing in resource-limited
      settings.
AB  - PURPOSE OF REVIEW: With the availability of antiretroviral drugs in resource
      limited settings, there is a rapid scale-up of antiretroviral therapy in
      developing countries. RECENT FINDINGS: The review focuses on the issues faced
      while patients are on first-line antiretroviral therapy in the absence of viral
      load monitoring, and the availability and progress of the second-line
      antiretroviral drugs and the salvage regimens in resource-limited settings.
      SUMMARY: There is an urgent need for low-cost, low-tech viral load monitoring in
      resource-limited settings. Fixed-dose combination of antiretrovirals for first
      line and second-line therapy will result in better effectiveness. There is a need
      for newer antiretroviral drugs in resource-limited settings.

PMID- 24100873
TI  - The 2013 WHO guidelines for antiretroviral therapy: evidence-based
      recommendations to face new epidemic realities.
AB  - PURPOSE OF REVIEW: The review summarizes the key new recommendations of the WHO
      2013 guidelines for antiretroviral therapy and describes the potential impact of
      these recommendations on the HIV epidemic. RECENT FINDINGS: The 2013 WHO
      guidelines recommend earlier initiation of antiretroviral therapy (ART) at CD4
      500 cells/MUl or less for all adults and children above 5 years. Further
      recommendations include initiation of ART irrespective of CD4 cell count or
      clinical stage for people co-infected with active tuberculosis disease or
      hepatitis B virus with severe liver disease, pregnant women, people in
      serodiscordant partnerships, and children under 5 years of age. The ART regimen
      comprising a once daily fixed-dose combination of tenofovir + lamivudine (or
      emtricitabine) + efavirenz is recommended as the preferred first-line therapy.
      Several approaches are also recommended to reach more people and increase health
      service capacity, including community and self-testing, and task shifting,
      decentralization, and integration of ART care. SUMMARY: If fully implemented, the
      2013 WHO ART guidelines could avert at least an additional 3 million deaths and
      prevent close to an additional 3.5 million new infections between 2012 and 2025
      in low- and middle-income countries, compared with previous treatment guidelines.

PMID- 24100874
TI  - Modeling the cost-effectiveness of HIV treatment: how to buy the most 'health'
      when resources are limited.
AB  - PURPOSE OF REVIEW: To summarize recent cost-effectiveness analyses (CEAs) that
      evaluate optimal treatment strategies for persons living with HIV/AIDS (PLWHA).
      RECENT FINDINGS: Efforts to attain universal coverage of current treatment
      guidelines (e.g., initiation at CD4 cell count <350 cells/MUl) are generally very
      costeffective. Expansion of access beyond current guidelines will additionally
      improve clinical outcomes and aversion of new HIV infections; however, cost
      effectiveness is more uncertain. Increasing access to antiretroviral therapy
      (ART) offers greater health benefit than investing the same funds in intensive
      laboratory monitoring for those on ART, particularly in those settings in which
      universal coverage has not yet been attained. Recommended ART regimens (e.g.,
      tenofovir) have favorable cost-effectiveness when compared with substitution of
      newer, more expensive agents (e.g., rilpivirine, darunavir) or substitution of
      older, cheaper alternatives that are more toxic (e.g., stavudine). SUMMARY: There
      is increasing use of CEA to evaluate decisions regarding HIV treatment in order
      to buy the most 'health' with limited resources. Expansion of ART access provides
      substantial clinical and preventive benefit and offers favorable cost
      effectiveness. Intensive laboratory monitoring may not be the highest priority in
      settings in which resources are constrained. Further work on the economic impact,
      clinical effectiveness, and feasibility of ART treatment for all (e.g., no CD4
      cell initiation criteria) is needed.

PMID- 24100875
TI  - Reformulation of existing antiretroviral drugs.
AB  - PURPOSE OF REVIEW: In the last decade, there has been marked progress in the
      treatment of HIV/AIDS. Today, nearly 10 million people are receiving ART. Yet,
      there are several opportunities for the enhancement of current antiretroviral
      (ARV) drugs by developing new formulations, which could increase bioavailability,
      reduce pharmacokinetic variability, and reduce the total daily dose. RECENT
      FINDINGS: Significant developments are occurring in new formulations of ARV
      drugs. The introduction of once daily combination pills and combination
      dispersible pills for children have been important steps. Several researchers and
      pharmaceutical companies are using nanomedicine for improved formulations and to
      reduce the dose. Other novel methods include intramuscular depot formulations,
      vaginal gels for prevention of transmission and sprinkle formulations for
      children. Regulatory approval, efficacy, safety and cost-effectiveness are
      factors that will have to be determined for the new formulations. Collaboration
      between pharmaceutical companies, academic centers, funding agencies and
      regulatory agencies will be crucial to achieve this goal. SUMMARY: In this
      review, we describe the objectives of new formulations, recent advances including
      combinations, copackaged drugs, nanomedicine, pediatric products and new routes
      of delivery and the challenges that lie ahead.

PMID- 24100876
TI  - Prodrug strategies for improved efficacy of nucleoside antiviral inhibitors.
AB  - PURPOSE OF REVIEW: This review focuses on the chemical and pharmacological
      rationale behind the development of nucleoside antiviral prodrugs (NAPs). RECENT
      FINDINGS: Highly efficacious NAPs have been developed that extend and improve the
      quality of lives of individuals infected with HIV and hepatitis B virus (HBV),
      herpes viruses, and adenovirus infection in immunocompromised individuals. A very
      high rate of hepatitis C virus (HCV) cure is now possible using NAPs combined
      with other direct acting antiviral agents (DAAs). SUMMARY: Prodrug strategies can
      address the issues of poor oral bioavailability and delivery of active
      metabolites to the targeted cells. Additionally, NAPs demonstrate potential for
      improving deficiencies in oral absorption, metabolism, tissue distribution,
      cellular accumulation, phosphorylation, and overall potency, in addition to
      diminishing potential for in-vivo selection of resistant viruses. NAPs continue
      to be the backbone for the treatment of HIV and HBV, herpesviruses, and
      adenovirus infections because their active forms are potent, have long
      intracellular half-lives and are relatively safe with high barrier to resistance.

PMID- 24100877
TI  - Long-acting injectable antiretrovirals for HIV treatment and prevention.
AB  - PURPOSE OF REVIEW: Long-acting antiretroviral (ARV) drugs may improve adherence
      to therapy and extend opportunities for therapeutic or prophylactic intervention
      to underserved patient populations. This review focuses on recent advances in the
      development of small molecule long-acting injectable ARV agents. RECENT FINDINGS:
      The need for combination ART and physicochemical and dosing limitations of
      current ARV drugs impede attempts to redevelop them as long-acting injectable
      formulations. However, the intrinsic properties of rilpivirine, a nonnucleoside
      reverse transcriptase inhibitor, and GSK1265744, an HIV-1 integrase strand
      transfer inhibitor, have enabled crystalline nanoparticle formulations to
      progress to clinical trials. SUMMARY: Investigational long-acting injectable
      nanoformulations of rilpivirine and GSK1265744 are clinical-stage development
      candidates. Complementary pharmacologic properties of both agents - different
      mechanisms of action, resistance profiles, metabolic pathways, lack of drug
      interactions and low daily oral doses - offer the potential for combination use.
      Phase I studies of the pharmacokinetics and safety of each long-acting
      formulation alone and in combination indicate that a monthly dosing regimen is
      possible for HIV treatment. An ongoing phase IIb trial of oral GSK1265744 and
      oral rilpivirine is evaluating this two-drug regimen for maintenance of virologic
      suppression; results will inform future studies using the injectable
      formulations. Additional preclinical and clinical studies indicate a potential
      use of each agent for HIV pre-exposure prophylaxis.

PMID- 24100878
TI  - Treatment optimization: an outline for future success.
AB  - PURPOSE OF REVIEW: In this issue of Current Opinion, the Guest Editors and their
      colleagues provide a comprehensive overview of current activities aimed at
      optimizing global HIV treatment. In this introduction, we outline current goals
      and approaches that will be described in more detail elsewhere in this issue.
      RECENT FINDINGS: Two recent conferences, the first and second Conference on
      Antiretroviral Drug Optimization (CADO), brought together experts from academia,
      governments, foundations, the pharmaceutical industry, and community activists to
      develop a global HIV-treatment research agenda for the coming decade focused on
      better therapies and how to make them accessible to a broader population of
      people living with HIV. Important recommendations included a focus on more
      efficient process chemistry for antiretroviral drugs, investigation of
      antiretroviral dose reduction as a possible optimization strategy, recognition of
      the increasing importance of concurrent infections and comorbidities especially
      tuberculosis and aging-related diseases, and identifying a highly effective and
      affordable nontoxic, once-daily fixed-dose combination regimen for first-line
      treatment. SUMMARY: HIV treatment optimization is a process intended to enhance
      the long-term efficacy, adherence, tolerability, safety, convenience, and
      affordability of combination ART. The ultimate goal of this process is to expand
      access to well tolerated and effective lifetime treatment to all those in need.

PMID- 24100879
TI  - The antiretroviral drug pipeline: prospects and implications for future treatment
      research.
AB  - PURPOSE OF REVIEW: A number of investigational antiretroviral drugs in clinical
      development could alter the future treatment landscape for resource-limited
      settings and contribute to optimized therapy for HIV infection. RECENT FINDINGS:
      Several nucleoside reverse transcriptase inhibitors (NRTIs) are in development,
      including festinavir (BMS-986001), a thymidine analogue similar to stavudine but
      with reduced potential for toxicity, CMX-157, a hexadecyloxypropyl conjugate of
      tenofovir and tenofovir alafenamide (GS-7340), a prodrug of tenofovir achieving
      much higher intracellular triphosphate concentrations with a lower dose than
      tenofovir disoproxil fumarate. MK-1439 is a well tolerated once-daily non-NRTI
      (NNRTI) with activity against most NNRTI-associated resistance mutations.
      Albuvirtide is a long-acting parenteral fusion inhibitor related to enfuvirtide,
      and BMS-663068 is an oral HIV attachment/entry inhibitor. Ibalizumab (formerly
      TNX-355) is an mAb that binds to CD4 and lowers HIV plasma viral RNA in infected
      patients. Cenicriviroc is a CCR5-antagonist that also has activity against the
      inflammatory chemokine CCR2. The integrase strand transfer inhibitor (InSTI)
      dolutegravir was recently approved in the U.S. and is an attractive component of
      future regimens because of efficacy, tolerability, apparent safety and once-daily
      dosing; it also maintains some activity against raltegravir and elvitegravir
      resistant mutants. The dolutegravir analogue GSK-1265744 appears to be equipotent
      and is being developed as a long-lasting injectable parenteral agent. The
      selective cytochrome P450 3A4 inhibitor cobicistat is a better tolerated
      alternative to ritonavir for pharmacokinetic 'boosting', but may also result in
      clinically undesirable drug interactions. SUMMARY: There are several
      investigational antiretroviral drugs with significant promise for inclusion in
      future primary and secondary combination regimens.

PMID- 24100881
TI  - An overview of the antiretroviral market.
AB  - PURPOSE OF REVIEW: An understanding of the current state of the antiretroviral
      marketplace is an important context in which to consider drug optimization work.
      RECENT FINDINGS: The antiretroviral marketplace has undergone a remarkable
      evolution over the past 11 years, expanding from serving less than 300 000
      patients in low and middle-income countries in 2002 to almost 10 million patients
      today. In addition to dramatic growth, a steady and rapid improvement in the
      drugs and drug regimens used to treat patients has characterized a rapidly
      changing market. SUMMARY: The antiretroviral marketplace has been characterized
      by rapid growth and a succession of improving drugs and regimens over the past 11
      years. The dynamic and innovative marketplace provides a strong platform from
      which to introduce new, optimized drugs and regimens to better serve patients'
      health needs.

PMID- 24100880
TI  - Pipeline of drugs for related diseases: tuberculosis.
AB  - PURPOSE OF REVIEW: For the first time in decades, there are multiple new drugs in
      the pipeline for the treatment of tuberculosis (TB). In addition, existing drugs
      are being repurposed or optimized for TB with the goal of shortened treatment
      duration for drug-sensitive TB and safer, shorter treatments for multidrug
      resistant (MDR) TB. In this review, the results of recent trials evaluating novel
      combination regimens for TB disease and latent TB infection are described. RECENT
      FINDINGS: High-dose rifamycins (rifampin and rifapentine) and fluoroquinolones
      directly observed have treatment-shortening potential when used for drug
      sensitive TB disease, and a 12-dose once-weekly regimen of rifapentine along with
      isoniazid effectively treats latent TB. Bedaquiline, an anti-TB drug with a novel
      mechanism of action, and delamanid, a nitroimidazole, are entering phase 3
      trials. Both improve rates of sputum culture conversion among patients with MDR
      TB. Other nitroimidazoles and oxazolidinones are in Phase 2 testing, as are
      combinations involving multiple new chemical entities. SUMMARY: With the
      resurgence of anti-TB drug discovery efforts, we now have a modestly robust
      pipeline of new anti-TB drugs. Several promising new regimens involving
      investigational and existing drugs that may be capable of shortening treatment
      for drug-sensitive TB and improving management of drug-resistant TB are in late
      phase clinical evaluation.

PMID- 24100882
TI  - Ocular vestibular evoked myogenic potentials n10 response in autism spectrum
      disorders children with auditory hypersensitivity: an indicator of semicircular
      canal dehiscence.
AB  - Sensitivity to sound is one of the most commonly reported challenges in ASD. No
      compelling evidence shows that hearing of ASD individuals differs physiologically
      from normal peers. Superior semicircular canal dehiscence was found to be more
      common in ASD children with auditory hypersensitivity (29%) by means of high
      resolution CT scan than the reported (14%) in normal pediatric population by
      other investigators. The increased prevalence of radiographic dehiscence might be
      due to inability of CT scan to visualize immature bone. We wished to determine
      whether ocular vestibular evoked myogenic potentials in ASD children with
      auditory hypersensitivity produces similar responses to those obtained in adult
      superior canal dehiscence, and whether it could help differentiate radiographic
      dehiscence due to bone immaturity from true canal dehiscence syndrome. A
      prospective study on 14 ASD children complaining of auditory hypersensitivity
      served as the study group. 15 ASD children without auditory hypersensitivity, age
      and gender matched, served as a control group. oVEMP and high-resolution CT scan
      of petrous and temporal bone were performed to all participants. Mean amplitude
      of n10 was 1.83 +/- 0.11 and 1.79 +/- 0.09 MUV in the control group with mean
      peak latency of 9.79 +/- 0.42 and 9.77 +/- 0.30 ms for the right and left ears,
      respectively. Asymmetry ratio was 2.04 +/- 1.37. In the study group, the mean
      amplitude of n10 was 2.07 +/- 0.46 and 1.89 +/- 0.30 MUV, with mean peak latency
      of 9.52 +/- 0.33 and 9.59 +/- 0.21 ms for the right and left ears, respectively,
      with asymmetry 5.23 +/- 6.93%. No statistically significant difference was
      observed for the studied parameters. In the study group, the number of ears
      showing an augmented amplitude (>2SD) of n10 was (N = 5). Furthermore, the study
      group demonstrated a radiographic SSCD in 6 ears. n10 was normal in the control
      group while radiographic SSCD was observed in 3 of them. CONCLUSION: oVEMPs show
      diagnostic ability in differentiating ASD children complaining of auditory
      hypersensitivity due to superior canal dehiscence from those with radiographic
      dehiscence only due to bone immaturity or atypical cortical development.

PMID- 24100883
TI  - Review of computational fluid dynamics in the assessment of nasal air flow and
      analysis of its limitations.
AB  - Nasal breathing difficulties (NBD) are a widespread medical condition, yet
      decisions pertaining to the surgical treatment of chronic NBD still imply a
      significant degree of subjective judgement of the surgeon. The current standard
      objective examinations for nasal flow, e.g., rhinomanometry and acoustic
      rhinomanometry, do not suffice to reliably direct the surgeon on the extent of
      any necessary surgery. In the last two decades, several groups have therefore
      considered the numerical simulation of nasal airflow. Currently, these analyses
      take many hours of labor from the operator, and require a huge amount of computer
      time and the use of expensive commercial software. Most often, their results are
      insufficiently validated so that virtual surgery, which is the eventual
      application, is still absent in clinical practice. Very recently, however,
      attempts at considering the finest details of the flow are beginning to appear,
      for example unsteady turbulent simulations validated through laboratory
      measurements through particle image velocimetry. In this paper, we first discuss
      recent developments in how computational fluid dynamics (CFD) is helping surgeons
      improve their understanding of nasal physiology and the effect of surgical
      modifications on the airflow in the nasal cavity. In a second part, the
      procedural and modeling challenges that still prevent CFD from being routinely
      used in clinical practice are surveyed and critically discussed. 

PMID- 24100884
TI  - Intensity of regionally applied tastes in relation to administration method: an
      investigation based on the "taste strips" test.
AB  - To compare various methods to apply regional taste stimuli to the tongue. "Taste
      strips" are a clinical tool to determine gustatory function. How a patient
      perceives the chemical environment in the mouth is a result of many factors such
      as taste bud distribution and interactions between the cranial nerves. To date,
      there have been few studies describing the different approaches to administer
      taste strips to maximize taste identification accuracy and intensity. This is a
      normative value acquisition pilot and single-center study. The investigation
      involved 30 participants reporting a normal sense of smell and taste (18 women,
      12 men, mean age 33 years). The taste test was based on spoon-shaped filter paper
      strips impregnated with four taste qualities (sweet, sour, salty, and bitter) at
      concentrations shown to be easily detectable by young healthy subjects. The
      strips were administered in three methods (held stationary on the tip of the
      tongue, applied across the tongue, held in the mouth), resulting in a total of 12
      trials per participant. Subjects identified the taste from a list of four
      descriptors, (sweet, sour, salty, bitter) and ranked the intensity on a scale
      from 0 to 10. Statistical analyses were performed on the accuracy of taste
      identification and rated intensities. The participants perceived in order of most
      to least intense: salt, sour, bitter, sweet. Of the four tastes, sour
      consistently was least accurately identified. Presenting the taste strip inside
      the closed mouth of the participants produced the least accurate taste
      identification, whereas moving the taste strip across the tongue led to a
      significant increase in intensity for the sweet taste. In this study of 30
      subjects at the second concentration, optimized accuracy and intensity of taste
      identification was observed through administration of taste strips laterally
      across the anterior third of the extended tongue. Further studies are required on
      more subjects and the additional concentrations prior to determining the ideal
      taste strip application method.

PMID- 24100885
TI  - Analysis of swallowing after partial frontolateral laryngectomy with epiglottic
      reconstruction for glottic cancer.
AB  - The aim of the study was to evaluate swallowing using a reproducible objective
      methodology and to seek preoperative factors that could influence swallowing
      outcomes in patients operated on for partial laryngectomy. Twenty-four patients
      who underwent partial frontolateral laryngectomy with epiglottic reconstruction
      for T1bN0 or T2N0 glottic carcinoma between 2008 and 2012 were retrospectively
      evaluated. Using fiberoptic endoscopic and videofluoroscopic evaluation, early
      (15 days postoperatively) and late (2 months postoperatively) scores were
      obtained for all patients to quantify their swallowing skills. Eighty-three
      percent of patients achieved at least partial oral feeding at time of hospital
      discharge and 87.5% achieved exclusive oral feeding within 2 months
      postoperatively. Early score was good or excellent in 50%, average in 4.2% and
      poor in 41.8%. Regarding late scores, 63% were classified as having a good or
      excellent late score, 7 patients (29%) were classified as "middle result" because
      their time to recover was longer (i.e. between 1 and 2 months postoperatively),
      and two patients had a poor late score. Finally, at last follow-up, only one
      patient was partially fed by gastrostomy (180 days after surgery). T stage (p =
      0.04) was the only factor influencing early swallowing outcomes and length of
      hospital stay was longer for poor scores than for good late results (p = 0.02).
      Our findings show good outcomes in terms of postoperative swallowing. Objective
      assessment of deglutition is essential for a better understanding of the
      mechanisms of postoperative swallowing disorders and for patient selection.

PMID- 24100886
TI  - Transcriptomic study of ciprofloxacin resistance in Streptomyces coelicolor
      A3(2).
AB  - Soil organisms exhibit resistance to a wide range of antibiotics as they either
      need to protect themselves from endogenous antibiotics or from those present in
      their soil environment. The soil could serve as a reservoir for resistance
      mechanisms that have already emerged or have the potential to emerge in
      clinically important bacteria. Streptomyces coelicolor, a non-pathogenic soil
      dwelling organism, is thus used as a model for the study of intrinsic resistance.
      Preliminary screening of several compounds showed that S. coelicolor had high
      intrinsic resistance for the fluoroquinolone group of antibiotics. We subjected
      the bacteria to sub-inhibitory concentrations of ciprofloxacin and studied the
      transcriptomic response using microarrays. The data were supported with various
      biochemical and phenotypic assays. Ciprofloxacin treatment leads to differential
      expression of many genes with enhanced mRNA expression of its target, DNA gyrase
      gene. High induction of DNA repair pathways was also observed and many
      transporters were upregulated. Ciprofloxacin was found to induce ROS formation in
      a dose dependent manner. Reduction of ROS via anti-oxidants increased the
      effective MIC of the drug in the bacteria. The regulation of antibiotic
      resistance in S. coelicolor was studied systematically and contribution of
      different mechanisms in the development of resistance was assessed. Our data
      suggest that multiple mechanisms work in coordination to facilitate the cell to
      combat the stress due to ciprofloxacin. 

PMID- 24100887
TI  - Pt-based core-shell nanocatalysts with enhanced activity and stability for CO
      oxidation.
AB  - This communication describes the synthesis of Pt@CeO2 core-shell catalysts for
      the application of highly efficient CO oxidation, where the 50% CO conversion
      temperature is lower than 200  degrees C. Pt@CeO2 is thermally stable as no
      deactivation occurs during the 70 h reaction, and the morphology is unchanged
      even after 700  degrees C thermal treatment. 

PMID- 24100890
TI  - [Use of recombinant human beta-defensin-3 to evaluate the effect of adhesion of
      Candida albicans on the surface of soft lining material].
AB  - PURPOSE: To evaluate the effectiveness of recombinant human beta-defensin-3
      (rHBD3) on reduction of Candida albicans from the surface of soft lining
      materials. METHODS: Specimens made of soft lining materials, which had been
      contaminated with C. albicans, were immersed in 25 MUg/mL rHBD3 and 5.25% sodium
      hypochlorite (a positive control) for 5, 10, 30 and 60 min. The results were
      analyzed statistically with SPSS 10.0 software package. Confocal laser scanning
      microscopy(CLSM) of biofilm-associated C. albicans were treated with rHBD3 in
      different times. RESULTS: The results confirmed that an immersion time of 30 min
      or higher yielded a good disinfection effect, both for the experimental group and
      the positive control. A large number of pathogenic bacteria were killed and the
      cells were stained red by SYTO9/PI after 30 min. CONCLUSIONS: It is possible that
      soft lining materials immersed in rHBD3 solution that possesses antifungal
      activity may be clinically protective.

PMID- 24100889
TI  - West nile virus antibody prevalence in horses of Ukraine.
AB  - West Nile virus (WNV) is a mosquito-borne virus of global importance. Over the
      last two decades, it has been responsible for significant numbers of cases of
      illness in humans and animals in many parts of the world. In Ukraine, WNV
      infections in humans and birds were first reported more than 25 years ago, yet
      the current epidemiological status is quite unclear. In this study, serum samples
      from over 300 equines were collected and screened in order to detect current WNV
      activity in Ukraine with the goal to estimate the risk of infection for humans
      and horses. Sera were tested by enzyme-linked immunosorbent assay (ELISA) and
      virus neutralization assay (NT) to detect WNV-specific antibodies. The results
      clearly revealed that WNV circulates in most of the regions from which samples
      were obtained, shown by a WNV seroprevalence rate of 13.5% of examined horses.
      This is the first topical report indicating the presence of WNV infections in
      horses in Ukraine, and the results of this study provide evidence of a widespread
      WNV circulation in this country. 

PMID- 24100892
TI  - [Osteoclasts and early bone remodeling after orthodontic micro-implant
      placement].
AB  - PURPOSE: To observe the incidence of osteoclasts during early bone remodeling
      after orthodontic micro-implant placement. METHODS: Twenty New Zealand rabbits
      were randomly allotted into 4 groups. One micro-implant was implanted proximal to
      the epiphyseal plate of the tibia. Animals were sacrificed on day 3, 7, 14 and 28
      (n=5). The sequence of histological changes around the micro-implants were
      evaluated by hematoxylin and eosin (HE) staining. Osteoclasts were identified by
      TRAP staining. The differences of the number of the osteoclasts among each time
      point were analyzed by one way ANOVA with SPSS 19.0 software package. RESULTS:
      After 3 days of implantation, a large number of erythrocytes, inflammatory cells,
      mesenchymal cells and bone debris were seen at the implant bone interfaces. Few
      osteoclasts were observed. On day 7, granular woven bone was formed and some
      osteoclasts were found in the Howship's lacunae. New bone formation and
      mineralization were apparent on day 14. Meanwhile, large amounts of osteoclasts
      were found in the latticed woven bone. On day 28, woven trabeculae with lamellate
      structures connected to lamellar bone and fewer osteoclasts were identified. Semi
      quantitative analysis showed that the number of the osteoclasts was at peak on
      day 14. There were significant differences among each time point (P<0.01).
      CONCLUSIONS: Osteoclast activity is closely related to bone formation and
      remodeling after micro-implant insertion.

PMID- 24100888
TI  - Non-structural proteins of arthropod-borne bunyaviruses: roles and functions.
AB  - Viruses within the Bunyaviridae family are tri-segmented, negative-stranded RNA
      viruses. The family includes several emerging and re-emerging viruses of humans,
      animals and plants, such as Rift Valley fever virus, Crimean-Congo hemorrhagic
      fever virus, La Crosse virus, Schmallenberg virus and tomato spotted wilt virus.
      Many bunyaviruses are arthropod-borne, so-called arboviruses. Depending on the
      genus, bunyaviruses encode, in addition to the RNA-dependent RNA polymerase and
      the different structural proteins, one or several non-structural proteins. These
      non-structural proteins are not always essential for virus growth and replication
      but can play an important role in viral pathogenesis through their interaction
      with the host innate immune system. In this review, we will summarize current
      knowledge and understanding of insect-borne bunyavirus non-structural protein
      function(s) in vertebrate, plant and arthropod. 

PMID- 24100891
TI  - [Repair of calvarial defect using a tissue-engineered bone with simvastatin
      loaded beta-tricalcium phosphate scaffold and adipose derived stem cells in
      rabbits].
AB  - PURPOSE: The osteogenic-angiogenic differentiation effects of simvastatin (Sim)
      were explored on adipose tissue-derived stem cells (ASCs). A tissue-engineered
      bone with simvastatin loaded beta-tricalcium phosphate (beta-TCP) scaffold and
      ASCs was constructed to repair the calvarial defect in rabbits. METHODS: ASCs
      were obtained from the groin of rabbits. After 14 days of osteogenic inducing
      culture, sufficient cells were expanded for the following experiments. Cell
      counting was conducted to ASCs in osteogenic inducing medium containing 0, 0.01,
      0.1 and 1 MUmol/L simvastatin. Concentrations of 0.05 and 0.1 MUmol/L simvastatin
      were administrated to ASCs for real-time PCR of angiogenesis-osteogenesis related
      genes like RUNX2, OPN, OCN, and VEGF on day 1, 7. ALP staining was performed on
      day 7, Alizarin red staining for calcium deposits was carried out on day 14.
      Bilateral critical-sized defects were created on 12 New Zealand rabbits. Four
      groups of tissue-engineered bone were randomly allocated to them. Group A: beta
      tricalcium phosphate (beta-TCP) (n=6); group B: beta-TCP/Cell (n=6); group C:
      beta-TCP/Sim (n=6); group D: beta-TCP/Cell/Sim (n=6). Specimens were decalcified
      and stained by HE 8 weeks after operation. The data was statistically analyzed
      using SPSS 17.0 software package. RESULTS: The use of simvastatin with the
      concentration of 0.05 MUmol/L enhanced the expression of angiogenic-osteogenic
      related genes like RUNX2, OPN, OCN, and VEGF. ALP activity and von Kossa were
      significantly stronger in osteogenic inducing medium containing 0.05 MUmol/L
      simvastatin. The new bone formation area of beta-TCP/Cell/Sim group at 8-week
      after implantation was significantly larger than the other groups. CONCLUSIONS:
      0.05 MUmol/L simvastatin enhances the angiogenic-osteogenic differentiation of
      ASCs. Simvastatin loaded beta-TCP scaffold and ASCs successfully repair the
      calvarial defect in rabbits. These results indicate a promising future in
      application of simvastatin for bone regeneration.

PMID- 24100893
TI  - [Three-dimensional finite element analysis of the upper cervical-defected incisor
      with labial access or lingual access].
AB  - PURPOSE: To evaluate the stress distribution of the cervical-defected incisor
      with labial or lingual endodontic access with finite element analysis (FEA), and
      to explore the advantage of resistance in labial endodontic access. METHODS: 3-D
      finite element models of upper cervical-defected incisor were established using
      cone-beam CT (CBCT), Mimics Catia, and Ansys software. The subjects were
      categorized according to the two endodontic accesses and three restorative ways,
      which were composite resin, glass fiber-reinforced composite resin and glass
      fiber-reinforced post-crown. All the models were loaded.The von Mises stress
      values and distribution were recorded and analyzed with Ansys 10.0 software.
      RESULTS: In this study, direct composite resin restoration showed no significant
      difference between the labial and lingual access. In glass fiber-reinforced
      composite resin, labial access could transfer the stress concentration area. It
      could reduce the incidence of fracture of the cervical lesion but increase the
      incidence of root fracture. Post-crown restoration could obviously reduce the
      incidence of fracture of the cervical lesion. CONCLUSIONS: When the cervical
      defected incisor is restored with composite resin, labial and lingual accesses
      can be considered. Labial access with glass fiber-reinforced composite resin or
      post-crown restoration is a good choice.

PMID- 24100894
TI  - [Effect of NF-kappaB on the expression of interleukin-6 induced by
      lipopolysaccharides of Porphyromonas endodontalis in MC3T3-E1 cells].
AB  - PURPOSE: To investigate the effect of NF-kappaB signaling on the expression of
      interleukin-6(IL-6) induced by lipopolysaccharides(LPS) extracted from
      Porphyromonas endodontalis(P.e) in MC3T3-El cells. METHODS: MC3T3-E1 cells were
      pretreated with BAY-117082 for 1 h, and then were treated with 10 mg/L P.e-LPS
      for different times. The translocation of NF-kappaB was observed by
      immunofluorescence. The expression of IL-6 was detected by reverse transcription
      polymerse chain reaction (RT-PCR) and enzyme-linked immuno sorbent assay (ELISA).
      Statistical analysis was performed using multi-way ANOVA and Dunnett's t test
      with SPSS 13.0 software package. RESULTS: The staining of NF-kappaB was mostly in
      cytoplasm in untreated cells. Rapid translocation of NF-kappaB into nucleus was
      observed in the cells stimulated for 30 min and mostly relocalization of NF
      kappaB from nucleus to cytoplasm was observed after 60 min. Pretreatment with 10
      MUmol/L BAY-117082 for 1h significantly inhibited P.e-LPS-induced translocation
      of NF-kappaB .The mRNA and proteins of IL-6 decreased significantly after
      pretreatment with 10 MUmol/L BAY-117082 and the expression of IL-6 proteins was
      reduced from (774.983+/-6.585) ng/L to (377.384+/-14.620) ng/L (P<0.01). The
      group of treatment with BAY-117082 alone had no significant difference from the
      blank control group. CONCLUSIONS: P.e-LPS can induce translocation of NF-kappaB
      in mouse osteoblast MC3T3-El, and P.e-LPS may induce the expression of IL-6 in
      mouse osteoblast through the signaling of NF-kappaB.

PMID- 24100895
TI  - [Dynamic analysis of the rigid fixed bridge and related tissue after intrusion of
      abutment with micro screw implant].
AB  - PURPOSE: To study the variety of mechanical behavior of fixed bridge after
      abutments being intruded by micro screw implant and to provide theoretical
      principles for clinical practice of teeth preparation after intrusion of
      abutments under dynamic loads. METHODS: Two-dimensional images of maxilla, teeth
      and supporting tissues of healthy people were scanned by spiral CT and were
      synthesized by Mimics10.01, Ansys13.0, etc. The three-dimensional finite element
      mathematical model of rigid fixed bridge repairing on double end of maxillary
      molar was developed. Under the condition of 10% simulative abutment alveolar
      absorption, vertical and oblique dynamic forces were applied in a circle of
      mastication(0.875 s) to build mathematical model after the abutment had been
      intruded for 0.5, 1.0, 1.5 and 2.0 mm. Stress variety of prosthesis, teeth,
      periodontal ligaments and supporting tissues were compared before and after
      intrusion of abutments. RESULTS: Stress variety of the prosthesis occurred, which
      had close relationship with the structure of prosthesis and teeth, the areas of
      periodontal ligaments increased, stress on the whole decreased along with the
      increase of the length of intrusion. With time accumulating, the stress value in
      prosthesis, teeth, periodontal ligaments and supporting tissues increased
      gradually and loads in oblique direction induced peak value stress in a
      masticatory cycle. Some residual stress left after unloading. CONCLUSIONS: By
      preparing the fixed bridge after abutment intrusion by micro screw implant, the
      service life of abutment and fixed bridge prosthesis can be reduced. The abutment
      and its related tissue have time-dependent mechanical behaviors during one
      mastication. The influence of oblique force on stress was greater than vertical
      force. There is some residual stress left after one mastication period. With the
      increase of the intrusion on abutment, residual stress reduced.

PMID- 24100896
TI  - [Three-dimensional finite element stress analysis of mandibular first molar with
      single and combined crowns after separation prosthodontic therapy].
AB  - PURPOSE: To evaluate the influence of two kinds of fixed prosthesis on the stress
      of the mandibular first molar with separation prosthodontic therapy. METHODS: A 3
      D finite element model of the mandibular first molar was established with single
      and combined crowns and their supporting tissues by means of cone-beam CT (CBCT)
      scanning technology and software Mimics, Geomagic, UG of image processing
      program. Under dispersed vertical load and dispersed oblique load, the stresses
      of dental tissues and periodontium were obtained and analysed. RESULTS: When
      dispersed vertical load was applied, the dental and periodontal stress
      distribution of two models were similar to the normal. The dental stress value
      and maximum tensile stress of the periodontal membrane increased and changed
      greatly in the single crown. When dispersed oblique load was applied, the model
      of combined crown was similar to the normal. The stress concentrated area
      expanded in the distal root of the single crown model and the buccal bottom half
      of the periodontium. The dental stress value and maximum tensile stress of the
      periodontal membrane increased and changed greatly in the single crown.
      CONCLUSIONS: The combined crown is a better choice for restoration of mandibular
      first molar after separation prosthodontic therapy.

PMID- 24100897
TI  - [Experimental evaluation of the spraying disinfection efficiency on dental
      models].
AB  - PURPOSE: To evaluate the disinfect effect after spraying a new kind of
      disinfectant on the dental plaster models. METHODS: The germ-free plaster
      samples, which were smeared with bacteria compound including Staphylococcus
      aureus, Escherichia coli, Saccharomyces albicans, Streptococcus mutans and
      Actinomyces viscosus were sprayed with disinfectants (CaviCide) and
      glutaraldehyde individually. In one group(5 minutes later) and another group(15
      minutes later), the colonies were counted for statistical analysis after
      sampling, inoculating, and culturing which were used for evaluation of
      disinfecting efficiency. ANOVA was performed using SPSS12.0 software package.
      RESULTS: All sample bacteria were eradicated after spraying
      disinfectants(CaviCide) within 5 minutes and effective bacteria control was
      retained after 15 minutes. There was significant difference between the
      disinfecting efficiency of CaviCide and glutaraldehyde. CONCLUSIONS: The effect
      of disinfection with spraying disinfectants (CaviCide) on dental models is quick
      and effective.

PMID- 24100898
TI  - [Effect of infiltration technique and polishing on the roughness of artificial
      carious enamel surfaces].
AB  - PURPOSE: To study the surface roughness of early carious lesions which were
      treated with resin infiltration and polished with different materials, and to
      provide reference for selection of appropriate polishing system. METHODS: Fifty
      four labial surface specimens of mandibular incisors were created out of bovine
      teeth. They were randomly divided into 6 groups. One group was sound enamel
      group. Another group was early enamel carious group. Other specimens were treated
      with a partially saturated acidic buffer solution for preparation of initial
      artificial enamel caries. These initial artificial enamel caries were treated
      with resin infiltration. Then they were randomly divided into 4 groups according
      to polishing or not and type of polishing tool (rubber cups, polishing discs,
      HiLuster polishers). The surface roughness of specimens in all groups were
      measured with Form Talysurf PGI 800. Arithmetical mean deviation of the assessed
      profile (Ra) and the maximum height of the profile(Rz) were used as measurement
      parameter. SPSS 17.0 software package was used for data analysis. RESULTS:
      Comparison of sound enamel surfaces and early carious surfaces revealed no
      significant difference in surface roughness(P>0.05), but the mean value of the
      latter one was higher. After infiltration, the roughness of surfaces without
      polishing was significantly higher than that of early carious surfaces(P<0.05).
      After infiltration and polishing with different tools, there was no significant
      difference in surface roughness of every two groups (P>0.05). The roughness of
      polishing groups after infiltration was significantly smaller than that of group
      without polished after infiltration (P<0.05). Comparison of polishing surfaces
      after infiltration and early carious surfaces revealed no significant difference
      in surface roughness (P>0.05). CONCLUSIONS: After early caries being treated with
      infiltration technique, the roughness of teeth surfaces increases significantly.
      Those surfaces should be polished. Rubber cup and polishing discs with smaller
      granularity are more effective and reasonable as the surface polishing materials.

PMID- 24100899
TI  - [The influence of Co-Cr-Mo alloys on biological behaviour of L929 mouse
      fibroblasts].
AB  - PURPOSE: To investigate the influence of dental Co-Cr-Mo alloys on biological
      behaviour of L929 mouse fibroblasts. METHODS: Leaching liquor of medical pure
      titanium, Co-Cr-Mo alloys, Co-Cr alloys and Ni-Cr alloys was prepared and used to
      culture the L929 cells for 24 h, 48 h and 72 h, respectively; then the growth of
      L929 cells was observed under inverted phase contrast microscope, and the
      cytotoxicity grades of 4 kinds of materials were evaluated by using CCK-8 test.
      The apoptosis of L929 cells was measured by flow cytometry(FCM) and acridine
      orange staining was used to observe the L929 cells adhered on the surface of
      samples under fluorescent microscope. The data was statistically analyzed with
      SPSS17.0 software package. RESULTS: Under inverted phase contrast microscope, at
      each time point, L929 cells grew in a good condition except in the Ni-Cr alloys
      group that minor karyopyknosis was indicating slight celluar cytotoxicity.
      Optical density (OD), apoptosis rate and cell adhesion number in Co-Cr-Mo alloys
      group at each time point were significantly less than in medical pure titanium
      group (P<0.05), and higher than in Co-Cr alloys group (P<0.05) and Ni-Cr alloys
      group (P<0.05). During observation period, the cytotoxicity grades of medical
      pure titanium group, Co-Cr-Mo alloys group and Co-Cr alloys group was grade 1,
      while Ni-Cr alloy group was grade 2, i.e. mild cytotoxicity. CONCLUSIONS: Co-Cr
      Mo alloys have no adverse effect on the biological behavior of L929 cells, which
      may be suitable for dental clinical application with good biocompatibility.

PMID- 24100900
TI  - [Effects of composite resin and glass-ionomer cements on proliferation and
      functional activity of human macrophages].
AB  - PURPOSE: To study the effects of composite resin and glass-ionomer cements on
      cell proliferation and function of human macrophages in vitro. METHODS:
      Macrophages were differentiated from THP-1 cells after treatment with phorbol
      ester and used as the model of inflammatory cells, which were treated by
      specimens from glass-ionomer cements(GC), composite resin Filtek Z350 (3M) and
      Filtek P60(3M) on culture medium for 24 hours. The cell proliferation of the
      tooth-colored restorative materials on human macrophages in vitro was evaluated
      by MTT color imetric assay, and determined for IL-1 content in these material
      specimens by ELISA. All statistical analyses were performed using the SPSS 17.0
      software package. RESULTS: Compared with control group, composite resin Filtek
      Z350(3M) and Filtek P60(3M) significantly enhanced the proliferation of human
      macrophages (P<0.05), while Glass-ionomer had little effect on the proliferation
      of human macrophages (P>0.05). Glass-ionomer could promote macrophages to secrete
      IL-1beta and the difference was statistically significant(P<0.05). The composite
      resin could not cause release of IL-1beta from macrophages (P>0.05). CONCLUSIONS:
      Composite resin enhances proliferation and function of human macrophages. The
      effect may be associated with hypersensitivity of dentin. Glass-ionomer cement
      has little effect on proliferation of macrophages, but may lead to progress of
      inflammation.

PMID- 24100901
TI  - [The prevalence of dehiscence and fenestration on anterior region of skeletal
      Class III malocclusions:a cone-beam CT study].
AB  - PURPOSE: To investigate the prevalence and distribution of alveolar bone
      dehiscence and fenestration in anterior region of skeletal Class III
      malocclusions. METHODS: The sample consisted of 19 males and 25 females with
      skeletal Class III malocclusions selected from consecutive patients of Department
      of Oral and Cranio maxillofacial Science from May 1st to June 1st, 2012. Five
      hundred and twenty-three teeth were examined by cone-beam CT (CBCT) in total
      while alveolar bone dehiscences and fenestrations were detected and measured
      using a new method. The data was processed using SAS8.02 software package.
      RESULTS: The prevalence of dehiscence was 61.57% in all teeth, while fenestration
      was 31.93% and the prevalence of defect (dehiscence or fenestration) was 77.44%.
      More defects were found in the mandible (58.52%) especially. The tooth site which
      was most commonly affected was lower canine, while the least was upper central
      incisor. No significant difference was found between both genders on most tooth
      sites of anterior region but more defects was found in lower central incisor and
      lower lateral incisor in male subjects. CONCLUSIONS: Alveolar defect is an
      extremely common finding in this sample. Whether alveolar defects such as
      dehiscence and fenestration are potential factors of root resorption and addition
      bone loss is still unclear, and further researches are needed.

PMID- 24100902
TI  - [A clinical study of osteotome sinus floor elevation and simultaneous implant
      placement in the periodontally compromised patients].
AB  - PURPOSE: To study the clinical effect of osteotome sinus floor elevation (OSFE)
      combined with simultaneous implant placement in the treatment of edentulous
      posterior maxilla subject to insufficient bone height in the periodontally
      compromised patients. METHODS: Forty-seven Straumanns implants were placed in the
      posterior maxilla in 35 patients with the procedure of OSFE. The final prostheses
      were restored after 3 to 6 months. The follow-up period was 6 to 30 months.
      Radiographs were taken and PD, PLI, BOP were measured and analyzed. RESULTS: The
      overall survival rate was 95.74% during the study period. Forty-five out of the
      47 implants were clinically stable and loaded without pain or any subjective
      sensation. The perforation ratio of the membrane was 4.26%. The average of PD
      around the implants was (3.22+/-1.07) mm. The average of the marginal bone loss
      was (1.38+/-0.59) mm. CONCLUSIONS: OSFE without bone graft proves to be an
      effective and predictable treatment for atrophic edentulous posterior maxillary
      region in patients with periodontitis, but the long-term effect needs further
      observation.

PMID- 24100903
TI  - [Comparison of the IL-27 level in gingival crevicular fluid of cross-quadrant and
      the upper and lower half-mouth subgingival scaling].
AB  - PURPOSE: To investigate the changes of IL-27 in gingival crevicular fluid (GCF)
      before and after treatment with different methods for chronic periodontitis.
      METHODS: Sixty patients with moderate or severe chronic periodontitis were
      selected as study group to divide into group A (cross-quadrant) and group B
      (upper and lower half-mouth) randomly. Another 30 healthy people were selected as
      group C. Gingival crevicular fluid of group A and B were collected at baseline
      and each week during treatment. At the same time, the clinical parameters
      including PD, AL, BI and PLI were recorded. And the levels of IL-27 in GCF were
      measured by ELISA. SPSS 17.0 software package was used for statistical analysis.
      RESULTS: The levels of IL-27 in GCF 2 and 3 weeks after treatment were higher in
      study group compared with those at baseline, while PD, AL, BI and PLI showed
      significant reduction. The changes except PLI in group A was more obvious than
      group B, which had a significant difference. After three-week treatment, IL-27 in
      group A had no remarkable difference compared with group C. There were
      significantly negative correlation between PD, AL, BI, PLI and IL-27.
      CONCLUSIONS: IL-27 in GCF can be considered as a potential target for prevention
      and treatment of chronic periodontitis. Compared with the upper and lower half
      mouth subgingival scaling, cross-quadrant has more pronounced short-term effect.

PMID- 24100904
TI  - [The relationship between Streptococcus sobrinus and rampant caries in children].
AB  - PURPOSE: To explore the relations between Streptococcus sobrinus (S. Sobrinus)
      and rampant caries in children. METHODS: Based on previous investigation result
      for rampant caries in Zhengzhou city, 66 children aged 3-5 years were selected by
      random sampling, and divided into 3 groups of rampant caries, high dental caries
      and no caries, 22 cases in each group. The final identification of S. mutans and
      S. sobrinus were performed after using culture medium TYCSB to operate
      preliminary screening of Streptococcus mutans (S. Mutans) and S. Sobrinus with
      polymerase chain reaction(PCR) combined with physiological and biochemical
      identification. SPSS10.0 software package was used to compare the detection rate
      and mean values of S.mutans and S.sobrinus in the experimental group and the
      control group. RESULTS: It was found that single S. sobrinus without S. mutans
      was not detected from dental plaque in each group. The detection rate of S.
      mutans in group of rampant caries was higher than in group of high dental caries,
      but there was no significant difference (P>0.05). The difference of detection
      rate of S. sobrinus between the two groups and the detection rate of S. mutans
      between group of rampant caries and group without caries was significant(P<0.05).
      The difference of the detection rate of S. sobrinus between group of rampant
      caries and group without caries was also significant(P<0.01). The incidence of
      rampant caries, DMFT, DMFS, smooth-surface caries among the sample with both of
      S. sobrinus and S. mutans detected and the sample only with S. mutans and the
      sample without S. sobrinus and S. mutans were significantly different (P<0.01).
      CONCLUSIONS: The main pathogenic bacteria of rampant caries in children are S.
      mutans and S. sobrinus. The incidence of rampant caries was related to S.
      sobrinus, which had synergic effect on the occurrence and development of rampant
      caries in children.

PMID- 24100905
TI  - [DNA repair gene polymorphisms in ERCC4 rs6498486 and ERCC5 rs751402 and risk of
      salivary gland tumors].
AB  - PURPOSE: To investigate the association between ERCC4 and ERCC5 polymorphisms and
      risk of salivary gland tumors. METHODS: Case-control study was carried out in 133
      cases of histologically confirmed salivary gland tumors and 142 age and gender
      matched healthy control cases. Polymorphisms of ERCC4 rs6498486 and ERCC5
      rs751402 were detected by PCR-RFLP. Multiple factors logistic regression analysis
      was conducted to investigate the association between gene polymorphisms and risk
      of salivary gland tumors using SPSS 18.0 software package. RESULTS: The genotype
      distribution of each polymorphism was found to be of Hardy-Weinberg equilibrium
      in the study. ERCC5 rs751402 TT genotype was associated with risk of salivary
      gland tumors (TT vs. CC+CT: OR=0.45, 95% CI: 0.21-0.98, P=0.046). No significant
      association was found in ERCC4 rs6498486. CONCLUSIONS: The results suggest that
      ERCC5 rs751402 polymorphism may be associated with risk of salivary gland tumors.

PMID- 24100906
TI  - [Computer aided design and computer aided manufacture of template for crown
      lengthening].
AB  - PURPOSE: To introduce a method applied in computer aided design and computer
      aided manufacture (CAD-CAM) of template for crown lengthening. METHODS: Point
      cloud data of dental stone model of the patient in the plan of crown lengthening
      surgery was obtained by laser scanning. The following processes were carried out,
      constructing 3-D curve of the gingiva, drawing template outline on the triangle
      mesh model, shelling it for 3-D model of template, and transferring the data to
      rapid prototyping equipment for manufacture. RESULTS: 3-D model of the template
      was preliminarily accomplished. The resin template was manufactured with rapid
      prototyping equipment. The fitness between resin template and plaster model was
      good. CONCLUSIONS: This method, as an integrated procedure including data
      acquisition, 3-D computer modeling and fabrication by rapid prototyping, is
      feasible to implement CAD-CAM of template for crown lengthening.

PMID- 24100907
TI  - [Evaluation of three-dimensional changes after sinus floor augmentation with
      DBBM].
AB  - PURPOSE: The objective of present study was to assess the dimensional stability
      of the grafting material DBBM (Bio-oss) after maxillary sinus floor augmentation
      with spiral computed tomography (SCT) scans and 3D reconstruction. METHODS: Two
      postoperative SCT scans were available from 12 patients who had undergone
      maxillary sinus lift procedures. CT scan was taken at 2 week after surgical
      intervention and 6 months later, respectively. A total of 12 maxillary sinuses
      were augmented with 100% DBBM before implant insertion by lateral antrostomy in a
      staged approach. The augmentation volume was calculated using the SurgiCase
      CMF5.0 software. Data were calculated by Stata10 software package. RESULTS: The
      mean volume of the graft was reduced by 19.40%. Specifically, the reduction
      reached 0.29% in the buccal-palatal direction, 5.87% in the mesial-distal
      dimension, and 14.32% in vertical dimension. CONCLUSIONS: This study confirmed
      that the volume of DBBM has a certain amount of reduction within 6 months after
      sinus floor augmentation. The reduction in vertical direction is most severe.

PMID- 24100908
TI  - [Application of joint reconstruction with autogenous coronoid process graft to
      treat temporomandibular joint ankylosis].
AB  - PURPOSE: To evaluate the clinical effect of joint reconstruction by using
      autogenous coronoid process graft to treat temporomandibular joint(TMJ)
      ankylosis. METHODS: Nine cases of TMJ ankylosis from September 2008 to September
      2010 were surgically treated by joint reconstruction with autogenous coronoid
      process graft, using autogenous articular disc or prosthodontic membrane as
      interpositional material. Mouth opening, occlusion and cone beam CT(CBCT) were
      used for evaluation before and after surgery. RESULTS: Satisfactory mouth opening
      was achieved in all patients and no one got occlusal changes or reankylosis
      during follow-up. CBCT showed that coronoid process graft reached bone union with
      the ramus and turned to be round. CONCLUSIONS: It is effective to cure TMJ
      ankylosis through joint reconstruction with autogenous coronoid process graft.

PMID- 24100909
TI  - [Gingival retraction paste versus gingival retraction cord for fixed
      prosthodontics: a systematic review].
AB  - PURPOSE: To assess the efficacy of gingival retraction paste versus gingival
      retraction cord in fixed prosthodontics on gingiva protection, tooth preparation,
      clarity of the impression and plaster model, and aptness of the prosthesis.
      METHODS: Chinese BioMedical Literature Database, VIP, China National Knowledge
      Infrastructure (CNKI) and Wangfang database were searched on November 15th 2012
      for eligible studies. Hand-searching included references of the included studies
      and Chinese dental journals. Risk of bias of the included studies was assessed by
      2 reviewers independently using Cochrane Collaboration's tool, and data
      extraction was done by the 2 reviewers. Meta analysis was performed with Revman
      5.1 software. RESULTS: Nine randomized controlled trials, involving 1153
      participants, were included. All of them had moderate risk of bias. Meta analysis
      revealed that gingival retraction paste had better effect on gingival health
      [RR=1.05, 95%CI (1.00, 1.11), P=0.04], tooth preparation [RR=1.17, 95%CI (1.07,
      1.28), P=0.0008] and clarity of the impression and plaster model [RR=1.08, 95%CI
      (1.03, 1.13), P=0.0009] than gingival retraction cord, and the aptness of the
      prosthesis was as good as the cord [RR=1.07, 95%CI (0.96, 1.19), P=0.21].
      CONCLUSIONS: The gingival retraction paste has better effect on gingival health,
      tooth preparation and clarity of the impression and plaster model, while the
      aptness of the prosthesis is as good as the cord and can be considered as a good
      candidate of the gingival retraction cord, but more randomized controlled trials
      are needed.

PMID- 24100910
TI  - [Application of problem-based learning in pre-job training of postgraduate
      students in department of endodontics].
AB  - PURPOSE: To apply problem-based learning (PBL) in pre-job training of
      postgraduate students in department of endodontics. METHODS: Thirty master degree
      postgraduate students of China Medical University were randomly divided into 2
      groups, there were 15 students in each group. One group were taught with PBL
      method while the other group with lecture-based learning (LBL) method. The
      teaching effect was measured with examination and questionnaire survey. The data
      were analyzed by student's t-test using SPSS 11.5 software package. RESULTS:
      There was no significant difference in basic knowledge, medical records writing,
      oral examination between the two groups (P>0.05). There were significant
      differences in case analysis, dental operation, theory examination, practical
      examination and total scores between the two groups (P<0.05). The PBL method was
      welcomed by master degree postgraduate students. CONCLUSIONS: The abilities of
      postgraduate students can be developed by PBL method in different aspects. PBL
      achieves satisfactory teaching effect, and can be applied in pre-job training of
      postgraduate students.

PMID- 24100911
TI  - [Application of autogenous artery to repair parotid duct defect].
AB  - PURPOSE: To use autogenous artery to repair parotid duct defect, and to
      investigate the clinical effect. METHODS: Anesthesia epidural catheter was used
      to support the parotid duct and a segment of superficial temporal artery was
      harvested to reconstruct the defect of the parotid duct. The patients were asked
      to revisit 1 month, 3 months, half a year and one year postoperatively. RESULTS:
      No swelling and salivary fistula was noted. The parotid ducts were successfully
      reconstructed with good patency and normal secretion. CONCLUSIONS: Using
      anesthesia epidural catheter to support the parotid duct, autogenous artery is
      excellent for repair of parotid duct defect.

PMID- 24100912
TI  - p75 neurotrophin receptor positive dental pulp stem cells: new hope for patients
      with neurodegenerative disease and neural injury.
AB  - Neurodegenerative diseases and neural injury are 2 of the most feared disorders
      that afflict humankind by leading to permanent paralysis and loss of sensation.
      Cell based treatment for these diseases had gained special interest in recent
      years. Previous studies showed that dental pulp stem cells (DPSCs) could
      differentiate toward functionally active neurons both in vitro and in vivo, and
      could promote neuranagenesis through both cell-autonomous and paracrine
      neuroregenerative activities. Some of these neuroregenerative activities were
      unique to tooth-derived stem cells and superior to bone marrow stromal cells.
      However, DPSCs used in most of these studies were mixed and unfractionated dental
      pulp cells that contain several types of cells, and most were fibroblast cells
      while just contain a small portion of DPSCs. Thus, there might be weaker ability
      of neuranagenesis and more side effects from the fibroblast cells that cannot
      differentiate into neural cells. p75 neurotrophin receptor (p75NTR) positive
      DPSCs subpopulation was derived from migrating cranial neural crest cells and had
      been isolated from DPSCs, which had capacity of differentiation into neurons and
      repairing neural system. In this article, we hypothesize that p75NTR positive
      DPSCs simultaneously have greater propensity for neuronal differentiation and
      fewer side effects from fibroblast, and in vivo transptantation of autologous
      p75NTR positive DPSCs is a novel method for neuranagenesis. This will bring great
      hope to patients with neurodegenerative disease and neural injury.

PMID- 24100913
TI  - [IgG4-associated parotitis:case report and review of the literature].
AB  - A case of immunoglobulin G4 (IgG4)-associated parotitis was reported and related
      literatures were reviewed,in order to improve the recognization of this systemic
      diseases and reduce the misdiagnosis and mistreatment in clinical practice for
      the stomatologists. 

PMID- 24100914
TI  - [Atypical solitary fibrous tumor of the buccal mucosa: report of 1 case].
AB  - Solitary fibrous tumor is often considered to be a mesenchymal tumor. We reported
      a case of atypical SFT of the buccal mucosa in a 56-year-old male patient. We
      found hypercellularity, nuclear atypia, increased number of mitotic figures(more
      than 4 per 10 high-power fields) microscopically. A long-term follow-up is
      necessary after complete excision. 

PMID- 24100915
TI  - Risk factors for depressive disorders in very old age: a population-based cohort
      study with a 5-year follow-up.
AB  - PURPOSE: Depressive disorders are common among the very old, but insufficiently
      studied. The present study aims to identify risk factors for depressive disorders
      in very old age. METHODS: The present study is based on the GERDA project, a
      population-based cohort study of people aged >=85 years (n = 567), with 5 years
      between baseline and follow-up. Factors associated with the development of
      depressive disorders according to DSM-IV criteria at follow-up were analysed by
      means of a multivariate logistic regression. RESULTS: At baseline, depressive
      disorders were present in 32.3 % of the participants. At follow-up, 69 % of those
      with baseline depressive disorders had died. Of the 49 survivors, 38 still had
      depressive disorders. Of the participants without depressive disorders at
      baseline, 25.5 % had developed depressive disorders at follow-up. Baseline
      factors independently associated with new cases of depressive disorders after 5
      years were hypertension, a history of stroke and 15-item Geriatric Depression
      Scale score at baseline. CONCLUSIONS: The present study supports the earlier
      findings that depressive disorders among the very old are common, chronic and
      malignant. Mild depressive symptoms as indicated by GDS-15 score and history of
      stroke or hypertension seem to be important risk factors for incident depressive
      disorders in very old age.

PMID- 24100916
TI  - What differentiates homeless persons who died by suicide from other suicides in
      Australia? A comparative analysis using a unique mortality register.
AB  - PURPOSE: To study the incidence of suicide by homeless persons over a 20-year
      period, and identify demographic and clinical characteristics that distinguish
      these cases from those in non-homeless persons. METHODS: A comparative analysis
      of homeless and non-homeless persons who died by suicide between 1990 and 2009 in
      Queensland, Australia. Ninety-two persons (82 males and 10 females) were
      identified from the Queensland Suicide Register as being homeless at the time of
      death. Suicide rates were calculated for the second decade only due to the lack
      of population numbers of homeless persons in the first decade. RESULTS: Homeless
      persons had almost twice higher suicide rate than non-homeless counterparts. They
      were more often male, of young age, single/never married, non-Indigenous,
      unemployed, had at least one physical illness or other stressful life event prior
      to death, had drug and alcohol abuse problems, and also were more likely to have
      evidence for an untreated mental illness. Regression analysis showed that being
      unemployed, having a history of legal problems and not being diagnosed with
      mental illness were strongly associated with suicide among homeless persons.
      CONCLUSIONS: This study is the first in Australia, and the second study
      internationally, to examine the characteristics of homeless people who died by
      suicide. Although based on a relatively small sample, the present work
      nonetheless carries practical implications for the development of targeted
      suicide prevention strategies in this peculiar population of individuals.

PMID- 24100918
TI  - Comparison of acetabular fracture reduction quality by the ilioinguinal or the
      anterior intrapelvic (modified Rives-Stoppa) surgical approaches.
AB  - OBJECTIVE: To compare the reduction quality, surgery time, and early
      postoperative complications between the 2 following surgical approaches: the
      ilioinguinal and the anterior intrapelvic (AIP or modified Rives-Stoppa). DESIGN:
      Retrospective study. PATIENTS: Comparison of 122 patients operated in our center
      between 1996 and 2003 with the ilioinguinal approach and 103 cases operated
      between 2004 and 2011 with the AIP approach. SETTING: Level 1 trauma center,
      acetabular fracture surgery referral center. OUTCOME MEASUREMENT: The patients'
      demographics, fracture type, fracture reduction quality, surgery time, and
      postoperative complications were compared. RESULTS: Anatomic reduction was
      achieved in 84 patients (68.9%) treated by the ilioinguinal approach and in 85
      patients (82.5%) treated by the AIP approach (P = 0.018). In both the columns,
      acetabular fracture type anatomic reduction was achieved in 54.2% of the
      ilioinguinal group and 79.4% of the AIP group (P = 0.018). In the ilioinguinal
      group, surgery time decreased as the number of surgeries increased (P = 0.021),
      whereas a similar trend was not found in the AIP group. Fracture type
      distribution and complication rates were similar for both the groups.
      CONCLUSIONS: The AIP approach is a safe alternative that offers better exposure
      and possibly improved reduction quality of acetabular fractures compared with the
      ilioinguinal approach. We believe that the major advantage of the AIP approach is
      that it enables reduction of the posterior column and the quadrilateral plate
      from the contralateral side and enables application of a buttress plate below the
      pelvic brim. LEVEL OF EVIDENCE: Therapeutic Level III. See Instructions for
      Authors for a complete description of levels of evidence.

PMID- 24100919
TI  - Association of systemic and intra-articular osteoclastogenic potential, pro
      inflammatory mediators and disease activity with the form of inflammatory
      arthritis.
AB  - PURPOSE: We aimed to assess osteoclastogenic potential of peripheral blood
      mononuclear cells (PBMC) and synovial fluid-derived mononuclear cells (SFMC) in
      different forms of arthritis and to correlate it with inflammatory mediators
      within intra-articular and circulatory compartments. METHODS: Paired PBMC and
      SFMC samples of patients with rheumatoid arthritis (RA; n = 10) and psoriatic
      arthritis (PsA; n = 10), and PBMC of healthy controls were cultured to assess
      osteoclastogenic potential by the number of tartrate-resistant acid phosphatase
      (TRAP)-positive osteoclasts (OCs) and expression of OC-related genes (receptor
      activator of nuclear factor-kappaBeta (RANK), cFMS, and TRAP). Osteoclastogenesis
      was correlated with the arthritis-related inflammatory indicators in serum and
      synovial fluid (SF). RESULTS: Number of OCs differentiated from PBMC was
      significantly higher in RA and PsA compared with control, with RA having more OCs
      compared with PsA. There was no difference in SFMC OC number between arthritic
      patients, but RANK expression in OCs differentiated from SFMC was higher in PsA
      compared with RA. SF of PsA patients more potently induced OC differentiation
      from control CD3(-)CD19(-)CD56(-)CD11b(+)CD115(+) PBMC compared with RA,
      paralleled with higher RANK-ligand expression in PsA SFMC. Positive correlations
      of OC number with erythrocyte sedimentation rate, serum level of CCL2, and PBMC
      gene expression of interleukin-18 and Fas-ligand were observed. CONCLUSION:
      Osteoclastogenic potential is systemically enhanced in patients with RA,
      paralleled by disordered systemic and local expression of proinflammatory
      mediators, whereas PsA involves specific deregulation in RANKL/RANK axis. Our
      study reveals arthritis-specific mediators associated with the form of arthritis,
      indicating clinical relevance for diagnosis and treatment.

PMID- 24100921
TI  - Violence against healthcare workers.

PMID- 24100920
TI  - Multiple arthroscopic debridement and graft retention in septic knee arthritis
      after ACL reconstruction: a prospective case-control study.
AB  - PURPOSE: This study was undertaken to prospectively analyse, at a mean five-year
      follow-up, the clinical, functional, and radiographic outcomes in patients who
      developed postoperative acute septic knee arthritis following anterior cruciate
      ligament (ACL) reconstruction using hamstring autograft. We also assessed the
      effect of multiple arthroscopic debridement and graft retention on the functional
      outcomes in comparison with the matched control group. METHODS: From a
      consecutive case series of 2,560 ACL-injured patients who were treated with
      arthroscopic ACL reconstruction, we report on 24 cases with postoperative septic
      knee arthritis. These patients were individually matched for age, sex,
      comorbidity, body mass index (BMI) and preinjury Tegner activity scale in a ratio
      of 1/1. Clinical, laboratory, synovial fluid analysis and culture were performed.
      Arthroscopic debridement and graft retention was done for all cases, in addition
      to antibiotic therapy i.v.. A detailed physical examination, KT1000 laxity
      testing, Lysholm knee score, Tegner activity level scale, International Knee
      Documentation Committee (IKDC), and Knee Injury and Osteoarthritis Outcome Score
      (KOOS) were completed. RESULTS: In all cases, treatment of infection was
      successful after a median of three (range one to six) repeated arthroscopic graft
      debridement and retention, in addition to antibiotic therapy i.v.. At an average
      of five years follow-up, two patients had over five millimetres manual maximum
      side-to-side difference in laxity. There were no significant differences between
      groups regarding Lysholm score, IKDC and KOOS. Median final Tegner activity score
      was 5.5 versus 7 in the control group (p = 0.004). Complications included graft
      rupture in three patients, loss of range of motion in five, Sudeck's atrophy in
      one and moderate joint narrowing in two. There were no recurrences of septic
      arthritis or bone infection. CONCLUSION: Graft retention seems not only possible
      but appropriate in view of the experience presented in this article for
      postoperative septic knee arthritis using hamstring autograft. A potential
      residual complication is arthrofibrosis, which deserves maximum attention.

PMID- 24100922
TI  - Retrospective comparison of three thromboprophylaxis agents, edoxaban,
      fondaparinux, and enoxaparin, for preventing venous thromboembolism in total knee
      arthroplasty.
AB  - PURPOSE: Patients undergoing total knee arthroplasty (TKA) are at high risk of
      venous thromboembolism, manifesting as deep vein thrombosis (DVT) or pulmonary
      embolism. The purpose of this study is to evaluate the efficacy and safety of
      edoxaban 15 mg once daily (o.d.) for preventing DVT in patients undergoing TKA.
      METHODS: Three hundred patients undergoing primary TKA under general anaesthesia
      for osteoarthritis were enrolled in this study: 100 treated with enoxaparin 2,000
      IU twice daily (b.i.d.), 100 treated with fondaparinux 1.5 mg o.d. and 100
      treated with edoxaban 15 mg o.d.. All treatments were scheduled to continue for
      14 days. RESULTS: The incidence of DVT in patients treated with edoxaban 15 mg
      o.d. was lower than in patients with enoxaparin 2,000 IU b.i.d. and fondaparinux
      1.5 mg o.d.. D-dimer levels were significantly lower in patients with edoxaban
      than in patients with enoxaparin and fondaparinux 1.5 mg o.d. on the first
      postoperative day; DeltaHb levels were lower in patients with edoxaban than in
      patients with enoxaparin and fondaparinux on postoperative days, However, the
      difference was not statistically significant. Finally, the incidence of hepatic
      dysfunction was lower in patients with edoxaban than in patients with enoxaparin
      and fondaparinux. CONCLUSIONS: Edoxaban 15 mg o.d. was more efficient than
      enoxaparin 2,000 IU b.i.d. and fondaparinux 1.5 mg o.d.. Furthermore, edoxaban
      was safe compared with enoxaparin and fondaparinux. Edoxaban, an orally
      administered direct factor Xa (FXa) inhibitor, may offer a new option for
      preventing DVT, with a level of evidence III.

PMID- 24100923
TI  - FTY720 for cancer therapy (Review).
AB  - 2-Amino-2-[2-(4-octylphenyl)]-1,3-propanediol hydrochloride (FTY720) is a potent
      immunosuppressant which has been approved by the Food and Drug Administration
      (FDA) as a new treatment for multiple sclerosis. As an immunosuppressant, it
      displays its anti-multiple sclerosis, immunosuppressive effects by activating
      sphingosine-1-phosphate receptors (S1PRs). In addition to the immunosuppressive
      effects, FTY720 also shows preclinical antitumor efficacy in several cancer
      models. In most cases, phosphorylation of FTY720 is not required for its
      cytotoxic effect, indicating the involvement of S1PR-independent mechanisms which
      are starkly different from the immunosuppressive property of FTY720. In the
      present study, we reviewed the rapidly advancing field of FTY720 in cancer
      therapy as well as some molecular targets of the unphosphorylated form of FTY720.

PMID- 24100924
TI  - Phase II trial of dose-dense chemotherapy followed by dose-intense erlotinib for
      patients with newly diagnosed metastatic non-small cell lung cancer.
AB  - This phase II study investigated dose-intense erlotinib maintenance after dose
      dense chemotherapy for patients with metastatic non-small cell lung cancer and
      examined two cell cycle biomarkers. Patients with newly diagnosed metastatic non
      small cell lung cancer received docetaxel 75 mg/m2 and cisplatin 75 mg/m2 on day
      1 and pegfilgrastim on day 2 every 14 days for four cycles. Patients then
      received erlotinib with initial doses based on smoking status. Doses were
      increased in 75 mg increments every two weeks depending on toxicities until each
      patient's maximal tolerable dose (MTD) was achieved. Cyclin D1 and D3 biomarkers
      were measured by immunohistochemistry. The objectives of the study were to
      evaluate time to progression (TTP) and overall survival (OS) for the entire
      population and biomarker subgroups. Forty-five patients were enrolled. Intra
      patient erlotinib MTD ranged from 0 to 525 mg. Median MTD achieved in smokers was
      higher than in non-smokers (300 vs. 150 mg; P=0.019). TTP for the entire cohort
      was not significantly improved compared to historical controls. Patients with
      high cyclin D1 expressing tumors demonstrated improved TTP on erlotinib (8.2 vs.
      4.7 months; hazard ratio, 4.1; 95% CI, 1.6-0.6; P=0.003) and improved OS (20.5
      vs. 8.0 months; hazard ratio 2.8; 95% CI, 1.2-6.3; P=0.016). Intratumoral cyclin
      D3 expression did not impact clinical outcomes. Current smokers but not former
      smokers exhibit a higher erlotinib MTD. High cyclin D1 expression was associated
      with favorable TTP and OS.

PMID- 24100925
TI  - Phenol ring nitration induced by the unprecedented reduction of the Cu(II) centre
      by nitrogen dioxide.
AB  - Nitrogen dioxide (NO2) induces tyrosine nitration through a radical mechanism in
      biological systems. Two copper(II) complexes, 1 and 2, with ligands L1 and L2 [L1
      = 2,4-di-tert-butyl-6-(((2-(dimethylamino)ethyl)(isopropyl)amino)methyl)phenol;
      L2 = 6,6'-(((2-(dimethylamino)ethyl)azanediyl)bis(methylene))bis(2,4-di-tert
      butylphenol)], respectively, have been made to react with NO2. In both cases, the
      reduction of the copper(II) center was observed in the presence of NO2 which
      induces phenol ring nitration through nitronium ion (NO2(+)) formation.

PMID- 24100926
TI  - Psychoneurochemical investigations to reveal neurobiology of memory deficit in
      epilepsy.
AB  - Pentylenetetrazole-kindling induced memory deficit has been validated in our
      previous study. The present study attempts a neurochemical investigation to
      reveal possible targets for treatment of memory deficit associated with
      pentylenetetrazole-kindling. Kindling was induced by administering subconvulsive
      dose of pentylenetetrazole (35 mg/kg; i.p.) at an interval of 48 +/- 2 h.
      Successfully kindled animals were divided into two groups (interictal and
      postictal group), while non-kindled (naive) animals served as naive group. In
      postictal group, animals were challenged with pentylenetetrazole (35 mg/kg) on
      days 5, 10, 15 and 20. Learning and memory were evaluated in all experimental
      groups using elevated plus maze and passive shock avoidance paradigm on days 5,
      10, 15 and 20. After behavioral evaluations on day 20, all animals were
      sacrificed to remove their brains. Neurochemical (glutamate, GABA,
      norepinephrine, dopamine and serotonin) changes and acetylcholinesterase activity
      and total nitrite level were estimated using HPLC-FD methods and microplate
      reader method respectively, in discrete brain parts. The results of the
      neurochemical estimation demonstrated the imbalance in excitatory/inhibitory
      tone, reduction in monoamine level, elevated nitrosative and acetylcholinesterase
      activity in the cortex and hippocampus, as responsible factors for the
      pathobiology of learning and memory deficit in epilepsy. Restoration of these
      changes may be targeted for the management of memory deficit in epileptic
      patients. 

PMID- 24100927
TI  - Increased hippocampal CREB phosphorylation in dopamine D3 receptor knockout mice
      following passive avoidance conditioning.
AB  - Dopamine D3 receptors (D3Rs) are implicated in synaptic plasticity and memory
      processes. Previously we have shown that D3Rs mediate inhibitory effects on
      learning, since D3R knockout (D 3 (-/-) ) mice display enhanced performance in
      the passive avoidance task (PA). Formation of new memories is known to require de
      novo synthesis of proteins related to synaptic function through the activation of
      signaling pathways including the mitogen-activated protein kinases (MAPKs) and
      activation of the nuclear transcription factor cAMP response element binding
      protein (CREB). However, there are no clear indications regarding the specific
      involvement of D3Rs in the activation of these signaling cascades after
      acquisition of PA. Therefore, in this study we assessed whether phosphorylation
      levels of several MAPKs, Akt and CREB were differentially affected by PA in both
      wild-type (WT) and D 3 (-/-) mice hippocampi. Animals were divided in Naive,
      unconditioned stimulus trained, conditioned stimulus trained and conditioned
      animals. Phosphorylation of extracellular signal-regulated kinase 1/2 (ERK 1/2),
      c-Jun-N-terminal kinase (JNK) and p38, as well as of Akt and CREB were
      determined. Acquisition of PA significantly increased pCREB levels both in WT and
      D 3 (-/-) mice. The extent of PA-driven increase in pCREB levels was
      significantly higher in mice lacking D3Rs. Similarly, pERK 1/2 was further
      augmented in trained D 3 (-/-) mice as compared to trained WTs, whereas JNK and
      p38 phosphorylation was not affected neither by PA nor by genetic background.
      Finally, Akt activation was observed in D 3 (-/-) mice, but not in response to
      PA. In conclusion, these data supports the notion that D3Rs might modulate CREB
      phosphorylation after acquisition of PA, probably via activation of ERK
      signaling. 

PMID- 24100928
TI  - Spontaneous peritoneal closure after orchidopexy in children : comment to:
      orchidopexy without ligation of the processus vaginalis is not associated with an
      increased risk of inguinal hernia. Ceccanti S, Zani A, Mele E and Cozzi DA
      (2013).

PMID- 24100929
TI  - Altered emotion processing circuits during the anticipation of emotional stimuli
      in women with borderline personality disorder.
AB  - Borderline personality disorder (BPD) is associated with disturbed emotion
      processing, typically encompassing intense and fast emotional reactions toward
      affective stimuli. In this study, we were interested in whether emotional
      dysregulation in BPD occurs not only during the perception of emotional stimuli,
      but also during the anticipation of upcoming emotional pictures in the absence of
      concrete stimuli. Eighteen female patients with a diagnosis of BPD and 18 healthy
      control subjects anticipated cued visual stimuli with prior known emotional
      valence or prior unknown emotional content during functional magnetic resonance
      imaging. Brain activity during the anticipation of emotional stimuli was compared
      between both groups. When anticipating negative pictures, BPD patients
      demonstrated less signal change in the left dorsal anterior cingulate cortex
      (dACC) and left middle cingulate cortex (MCC), and enhanced activations in the
      left pregenual ACC, left posterior cingulate cortex (PCC) as well as in left
      visual cortical areas including the lingual gyrus. During the anticipation of
      ambiguously announced stimuli, brain activity in BPD was also reduced in the left
      MCC extending into the medial and bilateral dorsolateral prefrontal cortex.
      Results point out that deficient recruitment of brain areas related to cognitive
      emotional interaction already during the anticipation phase may add to emotional
      dysregulation in BPD. Stronger activation of the PCC could correspond to an
      increased autobiographical reference in BPD. Moreover, increased preparatory
      visual activity during negative anticipation may contribute to hypersensitivity
      toward emotional cues in this disorder. 

PMID- 24100930
TI  - Intraobserver and interobserver agreement of computer software-assisted optic
      nerve head photoplanimetry.
AB  - PURPOSE: To report the reproducibility profile of optic nerve head parameters
      obtained by computer software-assisted fundus photoplanimetry. METHODS: Fundus
      photographs obtained during a population-based health survey (Sakurae Study) were
      planimetrically analyzed using newly developed computer software, CDSketch. The
      parameters assessed included vertical and horizontal cup-to-disc (C/D) ratios,
      superior and inferior rim-to-disc (R/D) ratios, disc and cup vertical-to
      horizontal (V/H) ratios, and disc-macular distance-to-disc diameter (DM/DD)
      ratio. For intraobserver and interobserver agreement assessments, we calculated
      the coefficients of variation (CVs) and intraclass correlation coefficients
      (ICCs) of the mean of three measurements obtained by one observer and a one-time
      measurement by three observers, respectively. RESULTS: The intraobserver CVs were
      between 2.4 % (DM/DD ratio) and 11.0 % (inferior R/D ratio), and the ICCs were
      between 0.868 (cup V/H ratio) and 0.976 (DM/DD ratio); all intraobserver ICCs had
      almost perfect agreement (>0.81). The interobserver CVs were between 2.6 % (disc
      V/H ratio) and 18.0 % (inferior R/D ratio), and the ICCs were between 0.762 (cup
      V/H ratio) and 0.930 (DM/DD ratio); the interobserver ICCs were categorized as
      substantial (0.61-0.80) for the inferior R/D and cup V/H ratios and as almost
      perfect for the other five parameters. CONCLUSIONS: The consistent profiles of
      the planimetric parameters suggest the suitability of software-assisted
      photoplanimetry for assessing optic disc characteristics in glaucoma clinical
      study and practice.

PMID- 24100931
TI  - Sentinel node biopsy after neoadjuvant chemotherapy: a new standard for patients
      with axillary metastases?

PMID- 24100932
TI  - Not so small vessel vasculitis.

PMID- 24100933
TI  - Outcome of eight-plate hemiepiphysiodesis on genu valgum and height correction in
      bilateral fibular hemimelia.
AB  - Fibular hemimelia is the most common lower extremity congenital longitudinal
      deficiency leading to cosmetic deformity, pain, and gait disturbance. Eight-plate
      hemiepiphysiodesis has proven to be successful in correcting angular deformity of
      the knee; it is an easy surgical technique and yields a more rapid rate of
      correction. The aim of this study was to determine the effectiveness of eight
      plate hemiepiphysiodesis in bilateral genu valgum resulting from fibular
      hemimelia and overall height improvement in two girls and four boys with a mean
      age of 22 months who were followed up for a period of 18 months. The variables
      studied were arm span, the total height ratio, intermalleolar distance,
      tibiofemoral angle, and activity. All the parameters improved significantly. The
      mean improvement in the valgus was 7.41 degrees . The mean intermalleolar
      distance reduced by 19.5 cm, and all patients achieved a significant improvement
      in lower limb function. Although there was significant improvement in total
      height, it still lagged behind arm span at the time of final follow-up. The
      results of eight-plate hemiepiphysiodesis were found to be satisfactory. We
      conclude that it is a reasonable treatment option for young patients with an
      adequate growth potential. 

PMID- 24100934
TI  - Effectiveness of financial incentives to improve adherence to maintenance
      treatment with antipsychotics: cluster randomised controlled trial.
AB  - OBJECTIVE: To test whether offering financial incentives to patients with
      psychotic disorders is effective in improving adherence to maintenance treatment
      with antipsychotics. DESIGN: Cluster randomised controlled trial. SETTING:
      Community mental health teams in secondary psychiatric care in the United
      Kingdom. PARTICIPANTS: Patients with a diagnosis of schizophrenia,
      schizoaffective disorder, or bipolar disorder, who were prescribed long acting
      antipsychotic (depot) injections but had received 75% or less of the prescribed
      injections. We randomly allocated 73 teams with a total of 141 patients. Primary
      outcome data were available for 35 intervention teams with 75 patients (96% of
      randomised) and for 31 control teams with 56 patients (89% of randomised).
      INTERVENTIONS: Participants in the intervention group were offered L15 (?17; $22)
      for each depot injection over a 12 month period. Participants in the control
      condition received treatment as usual. MAIN OUTCOME MEASURE: The primary outcome
      was the percentage of prescribed depot injections given during the 12 month
      intervention period. RESULTS: 73 teams with 141 consenting patients were
      randomised, and outcomes were assessed for 131 patients (93%). Average baseline
      adherence was 69% in the intervention group and 67% in the control group. During
      the 12 month trial period adherence was 85% in the intervention group and 71% in
      the control group. The adjusted effect estimate was 11.5% (95% confidence
      interval 3.9% to 19.0%, P=0.003). A secondary outcome was an adherence of >= 95%,
      which was achieved in 28% of the intervention group and 5% of the control group
      (adjusted odds ratio 8.21, 95% confidence interval 2.00 to 33.67, P=0.003).
      Although differences in clinician rated clinical improvement between the groups
      failed to reach statistical significance, patients in the intervention group had
      more favourable subjective quality of life ratings (beta=0.71, 95% confidence
      interval 0.26 to 1.15, P=0.002). The number of admissions to hospital and adverse
      events were low in both groups and did not show substantial differences.
      CONCLUSION: Offering modest financial incentives to patients with psychotic
      disorders is an effective method for improving adherence to maintenance treatment
      with antipsychotics. TRIAL REGISTRATION: Current Controlled Trials
      ISRCTN77769281.

PMID- 24100935
TI  - Sarcoglycans and integrins in bisphosphonate treatment: immunohistochemical and
      scanning electron microscopy study.
AB  - Osteonecrosis of the jaw is an adverse outcome associated with bisphosphonate
      treatment. Bisphosphonates are used in conjunction with antineoplastic
      chemotherapy for the treatment of hypercalcaemia associated with malignancy,
      lytic bone metastasis and multiple myeloma. However, it is not known if the
      osteonecrosis of the jaw lesion originates in the bone or whether it initiates in
      the gingival epithelium. Two bisphosphonates are commonly used in cancer
      treatment. One of these is pamidronate disodium, a second-generation
      bisphosphonate that differs from the first-generation drug because it inhibits
      bone resorption at a dose that does not affect bone mineralization. The other
      widely used BP, zoledronate, is a third-generation drug that is the most potent
      bisphosphonate in clinical use, showing strong anti-osteoclastic activity,
      similar to pamidronate. The aim of the present study was to evaluate the
      modifications of human oral mucosa and underlying bone in patients after
      treatment with these nitrogen-containing bisphosphonates for 24 and 36 months. We
      analyzed the structural damage of the oral mucosa and damage of the perilesional
      mandibular bone observing possible correlations from them. Our results allow to
      express two hypotheses about the mechanism responsible for these results relating
      to mandible matrix necrosis; first, an increased skeletal microdamage associated
      with turnover suppression occurred early in treatment and progress with longer
      treatment duration, second, opening damage in osteonecrosis of the jaw modifies
      structural morphology of gingival epithelium. 

PMID- 24100936
TI  - Behavior Change or Empowerment: On the Ethics of Health-Promotion Goals.
AB  - One important ethical issue for health promotion and public health work is to
      determine what the goals for these practices should be. This paper will try to
      clarify what some of these goals are thought to be, and what they ought to be. It
      will specifically discuss two different approaches to health promotion, such as,
      behavior change and empowerment. The general aim of this paper is, thus, to
      compare the behavior-change approach and the empowerment approach, concerning
      their immediate (instrumental) goals or aims, and to morally evaluate the
      strengths and weaknesses of these two goal models, in relation to the ultimate
      goal of health promotion. The investigation shows that the behavior-change
      approach has several moral problems. First of all, it is overly paternalistic and
      often disregards the individual's or group's own perception of what is important
      something that also increases the risk of failed interventions. Furthermore, it
      risks leading to 'victim blaming' and stigmatization, and to increased
      inequalities in health, and it puts focus on the 'wrong' problems, i.e., behavior
      instead of the 'causes of the causes'. It is thereafter shown that the
      empowerment approach does not have any of these problems. Finally, some specific
      problems for the empowerment approach are discussed and resolved, such as, the
      idea that empowering some groups might lead to power over others, the objection
      that the focus is not primarily on health (which it should be), and the fact that
      empowered people might choose to live lives that risk reducing their health. 

PMID- 24100937
TI  - Impact of perioperative renal dysfunction in heart transplantation: combined
      heart and kidney transplantation could help to reduce postoperative mortality.
AB  - BACKGROUND: Renal dysfunction is a frequent problem in heart failure patients. We
      aimed to investigate the predictors of mortality after heart transplantation and
      the impact of perioperative renal dysfunction on short-term and long-term
      prognosis. MATERIAL AND METHODS: We analyzed the outcomes of patients undergoing
      isolated heart transplantation (IHT, n=62) and combined heart-kidney
      transplantation (CHKT, n=5) between October 2007 and May 2012. Among all
      patients, 55.2% had preoperative renal dysfunction. RESULTS: Compared with the
      IHT group, the CHKT group had a lower estimated glomerular filtration rate
      (p=0.001), and higher proportion of diabetes (p=0.008), hypertension (p=0.010),
      renal failure (p=0.036), and greater incidence of preoperative continuous renal
      replacement therapy (CRRT) (p=0.025). Despite unfavorable baseline conditions in
      the CHKT group, there was no postoperative mortality. Early 30-day postoperative
      mortality only occurred in the IHT group (5 patients, 8.1%). In multivariate
      analysis, persistent renal dysfunction (HR 29.356, p<0.001), donor heart ischemic
      time (HR 1.014, p=0.005), and duration of mechanical ventilation (HR 1.012,
      p=0.026) were significant predictors of overall mortality. The patients with
      persistent renal dysfunction at 1 month after transplantation showed
      significantly lower survival rates compared to the patients with complete renal
      recovery (10% vs. 93% at 1 year, p<0.001). In the long-term follow-up of patients
      who had preoperative renal dysfunction, IHT showed only 64% survival, whereas
      CHKT showed 100%. CONCLUSIONS: Renal dysfunction was a common manifestation in
      heart transplantation recipients. Persistent renal dysfunction after
      transplantation was the most powerful independent predictor of overall mortality.
      CHKT could help to reduce postoperative mortality in end-stage heart failure
      patients with renal dysfunction.

PMID- 24100939
TI  - Pulmonary tumors associated with the JC virus T-antigen in a transgenic mouse
      model.
AB  - Many attempts to demonstrate the oncogenic role of the JC virus (JCV) have been
      partially successful in producing brain tumors, either by direct inoculation of
      JCV into the brain or in transgenic models in rodents. We previously reported the
      presence of JCV DNA with a relatively high incidence in pulmonary and digestive
      organs. However, we could not prove the oncogenic role of JCV. We prepared a
      transgene composed of the K19 promoter, specific to bronchial epithelium with the
      JCV T-antigen and established transgenic (TG) mice. Pulmonary tumors were
      detected without any metastasis in 2 out of 15 (13.3%) 16-month-old K19/JCV T
      antigen TG mice. Using immunohistochemistry (IHC), these tumors showed JCV T
      antigen, p53 and CK 19 expression, but not expression of nuclear and cytoplasmic
      beta-catenin and insulin receptor substrate 1 (IRS1). IHC revealed the same
      expression pattern as in the bronchial epithelium of the TG mice. One tumor,
      which was examined with laser capture microdissection and molecular biological
      tools, demonstrated an EGFR mutation but not a K-ras mutation. We propose that
      the pulmonary tumors were derived from the JCV T-antigen in a TG mouse model.
      These findings shed light on pulmonary carcinogenesis.

PMID- 24100940
TI  - Benign infantile convulsions (IC) and subsequent paroxysmal kinesigenic
      dyskinesia (PKD) in a patient with 16p11.2 microdeletion syndrome.
AB  - Paroxysmal kinesigenic dyskinesia with infantile convulsions (PKD/IC) is caused
      by mutations in the gene PRRT2 located in 16p11.2. A deletion syndrome 16p11.2 is
      well established and is characterized by intellectual disability, speech delay,
      and autism. PKD/IC, however, is extremely rare in this syndrome. We describe a
      case of PKD/IC and 16p11.2 deletion syndrome and discuss modifiers of PRRT2
      activity to explain the rare concurrence of both syndromes. 

PMID- 24100941
TI  - Neuroligin modulates the locomotory dopaminergic and serotonergic neuronal
      pathways of C. elegans.
AB  - Neuroligins are neuronal and neuromuscular transmembrane proteins that have been
      implicated in autism spectrum disorder and other cognitive diseases. The nlg-1
      gene from Caenorhabditis elegans is orthologous to human neuroligin genes. In the
      nematode, the locomotory rate is mediated by dopaminergic and serotonergic
      pathways, which result in two different behavioral responses known as basal
      slowing response (BSR) and enhanced slowing response (ESR), respectively. We
      report that nlg-1-deficient mutants are defective in both the BSR and ESR
      behaviors. In addition, we demonstrate that methylphenidate (a dopamine reuptake
      inhibitor) and fluoxetine (a serotonin reuptake inhibitor), two drugs widely used
      for the treatment of behavioral disorders in humans, are able to restore the BSR
      and ESR wild type phenotypes, respectively, in nlg-1 defective mutant nematodes.
      The abnormal locomotory behavior patterns were rescued in nlg-1-deficient mutant
      by expressing a cDNA from the human NLGN1 gene under the C. elegans nlg-1
      promoter. However, human NLGN1 (R453C) and NLGN1 (D432X) mutant alleles did not
      rescue any of the two mutant phenotypes. The results indicate that neuroligin is
      involved in modulating the action of dopamine and serotonin in the nematode and
      suggest that the functional mechanism underpinning both methylphenidate and
      fluoxetine in C. elegans might be comparable to that in humans. The neuroligin
      deficient mutants may undergo inefficient synaptic transmissions which could
      affect different traits in the nervous system. In particular, neuroligin might be
      required for normal neurotransmitters release. The understanding of the
      mechanisms by which methylphenidate and fluoxetine are able to restore the
      behavior of these mutants could help to explain the etiology of some human
      neurological diseases. 

PMID- 24100942
TI  - Science and management of the introduced seagrass Zostera japonica in North
      America.
AB  - Healthy seagrass is considered a prime indicator of estuarine ecosystem function.
      On the Pacific coast of North America, at least two congeners of Zostera occur:
      native Zostera marina, and introduced, Zostera japonica. Z. japonica is
      considered "invasive" and therefore, ecologically and economically harmful by
      some, while others consider it benign or perhaps beneficial. Z. japonica does not
      appear on the Federal or the Oregon invasive species or noxious weed lists.
      However, the State of California lists it as both an invasive and noxious weed;
      Washington State recently listed it as a noxious weed. We describe the management
      dynamics in North America with respect to these congener species and highlight
      the science and policies behind these decisions. In recent years, management
      strategies at the state level have ranged from historical protection of Z.
      japonica as a priority habitat in Washington to eradication in California. Oregon
      and British Columbia, Canada appear to have no specific policies with regard to
      Z. japonica. This fractured management approach contradicts efforts to conserve
      and protect seagrass in other regions of the US and around the world. Science
      must play a critical role in the assessment of Z. japonica ecology and the
      immediate and long-term effects of management actions. The information and
      recommendations provided here can serve as a basis for providing scientific data
      in order to develop better informed management decisions and aid in defining a
      uniform management strategy for Z. japonica. 

PMID- 24100943
TI  - Yb3+ sensitized Er3+ doped La2O3 phosphor in temperature sensors and display
      devices.
AB  - The frequency upconversion emissions in the Er(3+)/Er(3+)-Yb(3+) doped/codoped
      hexagonal shaped La2O3 phosphor characterized by X-ray diffraction (XRD) upon
      excitation with 980 nm and 800 nm CW lasers have been investigated. The
      upconversion emissions corresponding to the (2)H(9/2) -> (4)I(15/2), (2)H(11/2) 
      > (4)I(15/2), (4)S(3/2) -> (4)I(15/2) and (4)F(9/2) -> (4)I(15/2) transitions
      peaking at 409 nm, 523 nm, 548 nm and 660 nm have been observed under 980 nm
      excitation whereas 523 nm, 548 nm and 660 nm upconversion emission bands have
      been visualized under 808 nm excitation. The upconversion emission intensity of
      Er(3+) ions is enhanced by several times due to the codoping with Yb(3+) ions,
      under 980 nm excitation while there is a reduction in intensity in the codoped
      sample under 808 nm excitation. The decay curve analysis for the green UC
      emission band corresponding to the (4)S(3/2) -> (4)I(15/2) transition in the
      Er(3+)/Er(3+)-Yb(3+) doped/codoped La2O3 phosphor upon 980 nm excitation has been
      done. The colour coordinate of the phosphor sample has been calculated at
      different pump powers and its value is observed to be almost similar to that of
      the standard green colour and also independent of the excitation power density.
      The effect of temperature on the upconversion emission intensity of the green
      emissions has been determined and noted that the present phosphor material can be
      used in making temperature sensing device upto 600 K.

PMID- 24100944
TI  - Evaluating the Berlin Definition in pediatric ARDS.

PMID- 24100945
TI  - The influence of continuous venovenous renal replacement therapy on the plasma
      disappearance rate of indocyanine green.

PMID- 24100947
TI  - Efficient and stable CH3NH3PbI3-sensitized ZnO nanorod array solid-state solar
      cells.
AB  - We report for the first time the use of a perovskite (CH3NH3PbI3) absorber in
      combination with ZnO nanorod arrays (NRAs) for solar cell applications. The
      perovskite material has a higher absorption coefficient than molecular dye
      sensitizers, gives better solar cell stability, and is therefore more suited as a
      sensitizer for ZnO NRAs. A solar cell efficiency of 5.0% was achieved under 1000
      W m(-2) AM 1.5 G illumination for a solar cell with the structure: ZnO
      NRA/CH3NH3PbI3/spiro-MeOTAD/Ag. Moreover, the solar cell shows a good long-term
      stability. Using transient photocurrent and photovoltage measurements it was
      found that the electron transport time and lifetime vary with the ZnO nanorod
      length, a trend which is similar to that in dye-sensitized solar cells, DSCs,
      suggesting a similar charge transfer process in ZnO NRA/CH3NH3PbI3 solar cells as
      in conventional DSCs. Compared to CH3NH3PbI3/TiO2 solar cells, ZnO shows a lower
      performance due to more recombination losses. 

PMID- 24100946
TI  - The use of the Berlin definition for acute respiratory distress syndrome during
      infancy and early childhood: multicenter evaluation and expert consensus.
AB  - PURPOSE: A new acute respiratory distress syndrome (ARDS) definition has been
      recently issued: the so-called Berlin definition (BD) has some characteristics
      that could make it suitable for pediatrics. The European Society for Pediatric
      Neonatal Intensive Care (ESPNIC) Respiratory Section started a project to
      evaluate BD validity in early childhood. A secondary aim was reaching a consensus
      on clinical tools (risk factors list and illustrative radiographs) to help the
      application of BD. METHODS: This was an international, multicenter, retrospective
      study enrolling 221 children [aged greater than 30 days and less than 18 months;
      median age 6 (range 2-13) months], admitted to seven European pediatric intensive
      care units (PICU) with acute lung injury (ALI) or ARDS diagnosed with the earlier
      definition. RESULTS: Patients were categorized according to the two definitions,
      as follows: ALI, 36; ARDS, 185 (for the American-European Consensus Conference
      (AECC) definition); mild, 36; moderate, 97; severe ARDS, 88 (for BD). Mortality
      (13.9 % for mild ARDS; 11.3 % for moderate ARDS; 25 % for severe ARDS, p = 0.04)
      and the composite outcome extracorporeal membrane oxygenation (ECMO)/mortality
      (13.9 % for mild ARDS; 11.3 % for moderate ARDS; 28.4 % for severe ARDS, p <
      0.01) were different across the BD classes, whereas they were similar using the
      previous definition. Mortality [HR 2.7 (95 % CI 1.1-7.1)] and ECMO/mortality [HR
      3 (95 % CI 1.1-7.9)] were increased only for the severe ARDS class and remained
      significant after adjustment for confounding factors. PICU stay was not different
      across severity classes, irrespective of the definition used. There was
      significant concordance between raters evaluating radiographs [ICC 0.6 (95 % CI
      0.2-0.8)] and risk factors [ICC 0.92 (95 % CI 0.8-0.97)]. CONCLUSIONS: BD
      validity for children is similar to that already reported in adults and mainly
      due to the introduction of a "severe ARDS" category. We provided clinical tools
      to use BD for clinical practice, research, and health services planning in
      pediatric critical care.

PMID- 24100948
TI  - Growing hyperbranched polymers using natural sunlight.
AB  - In nature, a sapling can grow into a big tree under irradiation of sunlight. In
      chemistry, a similar concept that a small molecule only exposing to sunlight
      grows into a hyperbranched macromolecule has not been realized by now. The
      achievement of the concept will be fascinating and valuable for polymer synthesis
      wherein sunlight is inexpensive, abundant, renewable, and nonpolluting. Herein,
      we report a new strategy in which small monomers can directly grow into big
      hyperbranched macromolecule under irradiation of sunlight without any catalyst. 

PMID- 24100949
TI  - Investigating a pathogenic role for TXNDC5 in tumors.
AB  - The expression of TXNDC5, which is induced by hypoxia, stimulates cell
      proliferation and angiogenesis. The increased cell proliferation, angiogenesis
      and hypoxia are main features of tumor tissues. The present study aimed to
      characterize the expression of TXNDC5 in various tumor types and to investigate
      the role of TXNDC5 in the growth, proliferation and migration of tumor cells. The
      study also determined susceptibility of TXNDC5 gene on tumor risk. The expression
      of TXNDC5 in tumor tissues was determined by immunohistochemistry using a tissue
      array that contained various types of tumor tissues. The expression levels of
      TXNDC5 in tumor tissues and healthy tissues were quantitatively analyzed using
      western blotting. Furthermore, HeLa cells and U2OS cells were treated with anti
      TXNDC5 siRNA to knockdown the expression levels of TXNDC5 to study its role in
      cell proliferation and migration. The cell proliferation and migration of the
      transfected tumor cells were determined by MTT and Transwell migration assays,
      respectively. Ninety-six tag SNPs across the TXNDC5 locus were genotyped using
      custom-designed Illumina 384-SNP VeraCode microarrays. Our immunohistochemical
      staining revealed significant expression of TXNDC5 in breast invasive ductal
      carcinomas, cervical squamous cell carcinomas, esophageal squamous cell
      carcinomas, gastric carcinomas, hepatocellular carcinomas, ovarian papillary
      serous carcinomas, prostate cancers and undifferentiated cell carcinomas of the
      lung. Western blot analysis also detected significantly higher TXNDC5 expression
      in tumor tissues of breast cancers, gastric adenocarcinomas and rectal cancers
      compared to the adjacent healthy tissues. Decreased growth and invasive potential
      were observed in cultured HeLa cells and U2OS cells when TXNDC5 gene expression
      was knocked down. The case-control analysis showed a significant difference in
      allele frequency and genotype frequency for rs9505298, rs7771314, rs2815128,
      rs13210097 and rs9392182 between cervical carcinoma, esophageal carcinoma and
      liver cancer patients and controls. These results suggest that TXNDC5 has
      increased expression in many tumors that is involved in the proliferation and
      migration of tumor cells, acting as a tumor-enhancing gene. The study also
      suggests that TXNDC5 gene is susceptible to cervical carcinoma, esophageal
      carcinoma and liver cancer risk. 

PMID- 24100950
TI  - Insight into polycation chain length affecting transfection efficiency by O
      methyl-free N,N,N-trimethyl chitosans as gene carriers.
AB  - PURPOSE: The structure-function relationship and mechanism of polycations as gene
      carriers have attracted considerable research interest in recent years. The
      present study was to investigate the relationship between polycation chain length
      and transfection efficiency (RCL-TE), and the corresponding mechanism by O-methyl
      free N,N,N-trimethyl chitosans (TMCs) as gene carriers. METHODS: Four TMCs with
      various chain lengths were synthesized and used to evaluate the RCL-TE. To
      investigate the details of RCL-TE, a number of factors such as cytotoxicity,
      cellular uptake efficiency, cellular uptake pathway and intracellular
      trafficking, were evaluated. RESULTS: In comparison to short chain length TMCs (S
      TMCs), long chain length ones (L-TMCs) mediated higher gene expression. The
      polyplexes formed by L-TMCs and pDNA showed higher stability. The cellular uptake
      pathway and intracellular trafficking of these TMC/pDNA polyplexes were
      different. These above factors are probably the key ones in RCL-TE rather than
      polycation-DNA binding affinity, polyplex particle size in water, zeta potential,
      serum, cytotoxicity, and cellular uptake efficiency. CONCLUSIONS: For rational
      design of chitosan-based polycations as gene carriers, polycations with relative
      long chain lengths are more favorable and more attention should be paid to
      polyplex stability, function of uncomplexed polycation chains, cellular uptake
      pathway, and intracellular trafficking.

PMID- 24100951
TI  - Radio-sensitization of human leukaemic MOLT-4 cells by DNA-dependent protein
      kinase inhibitor, NU7441.
AB  - We studied the effect of pre-incubation with NU7441, a specific inhibitor of DNA
      dependent protein kinase (DNA-PK), on molecular mechanisms triggered by ionizing
      radiation (IR). The experimental design involved four groups of human T
      lymphocyte leukaemic MOLT-4 cells: control, NU7441-treated (1 MUM), IR-treated (1
      Gy), and combination of NU7441 and IR. We used flow cytometry for apoptosis
      assessment, Western blotting and ELISA for detection of proteins involved in DNA
      repair signalling and epifluorescence microscopy for detection of IR-induced
      phosphorylation of histone H2A.X. We did not observe any major changes in the
      amount of DNA-PK subunits Ku70/80 caused by the combination of NU7441 and
      radiation. Their combination led to an increased phosphorylation of H2A.X, a
      hallmark of DNA damage. However, it did not prevent up-regulation of neither p53
      (and its phosphorylation at Ser 15 and 392) nor p21. We observed a decrease in
      the levels of anti-apoptotic Mcl-1, cdc25A phosphatase, cleavage of PARP and a
      significant increase in apoptosis in the group treated with combination. In
      conclusion, the combination of NU7441 with IR caused increased phosphorylation of
      H2A.X early after irradiation and subsequent induction of apoptosis. It was
      efficient in MOLT-4 cells in 10* lower concentration than the inhibitor NU7026.
      NU7441 proved as a potent radio-sensitizing agent, and it might provide a
      platform for development of new radio-sensitizers in radiotherapy.

PMID- 24100952
TI  - Preliminary findings of cortical thickness abnormalities in blast injured service
      members and their relationship to clinical findings.
AB  - Though cortical abnormalities have been demonstrated in moderate and severe
      traumatic brain injured (TBI) patients, there have been no studies examining
      cortical changes following blast related mild TBI (mTBI). The purpose of this
      study was to determine the effects and functional relevance of blast mTBI on
      cortical thickness in a small cohort of carefully screened blast injured US
      Service Members (SM). Twelve SM with mTBI acquired through blast injury were
      compared to 11 demographically matched control SM without TBI. Both mTBI and
      control participants were active duty and had completed a combat deployment.
      Subjects underwent MRI examination and the T1 weighted anatomic images were
      processed using the FreeSurfer suite of tools. Cortical thickness maps were
      compared between groups and examined for relationships with time since injury
      (TSI). Utilizing a large database of functional imaging results (BrainMap),
      significant regions of interest (ROI) were used to determine the behavioral
      profiles most consistently associated with the specific ROI. In addition,
      clinical variables were examined as part of post-hoc analysis of functional
      relevance. Group comparisons controlling for age demonstrated several significant
      clusters of cortical thinning for the blast injured SM. After multiple
      comparisons correction (False Discovery Rate (FDR)), two left hemisphere clusters
      remained significant (left superior temporal (STG) and frontal (SFG) gyri). No
      clusters were significantly correlated with TSI after FDR correction. Behavioral
      analysis for the STG and SFG clusters demonstrated three significant
      behavioral/cognitive sub-domains, each associated with audition and language.
      Blast injured SMs demonstrated distinct areas of cortical thinning in the STG and
      SFG. These areas have been previously shown to be associated with audition and
      language. Post-hoc analyses of clinical records demonstrated significant abnormal
      audiology reports for the blast injured SM suggesting that the thinning in these
      ROIs might be related to injury to the external auditory system rather than
      direct injury to the brain from the blast. It is clear that additional
      replication is needed in much larger cohorts. Importantly, the combination of
      imaging tools and methods in this study successfully demonstrated the potential
      to define unique ROIs and functional correlates that can be used to design future
      studies. 

PMID- 24100953
TI  - Modeling the impact of alternative strategies for rapid molecular diagnosis of
      tuberculosis in Southeast Asia.
AB  - Novel diagnostic tests hold promise for improving tuberculosis (TB) control, but
      their epidemiologic impact remains uncertain. Using data from the World Health
      Organization (2011-2012), we developed a transmission model to evaluate the
      deployment of 3 hypothetical TB diagnostic tests in Southeast Asia under
      idealized scenarios of implementation. We defined diagnostics by their
      sensitivity for smear-negative TB and proportion of patients testing positive who
      initiate therapy ("point-of-care amenability"), with tests of increasing point-of
      care amenability having lower sensitivity. Implemented in the public sector (35%
      of care-seeking attempts), each novel test reduced TB incidence by 7%-9% (95%
      uncertainty range: 4%-13%) and mortality by 20%-22% (95% uncertainty range: 14%
      27%) after 10 years. If also deployed in the private sector (65% of attempts),
      these tests reduced incidence by 13%-16%, whereas a perfect test (100%
      sensitivity and treatment initiation) reduced incidence by 20%. Annually
      detecting 20% of prevalent TB cases through targeted screening (70% smear
      negative sensitivity, 85% treatment initiation) also reduced incidence by 19%.
      Sensitivity and point-of-care amenability are equally important considerations
      when developing novel diagnostic tests for TB. Novel diagnostics can
      substantially reduce TB incidence and mortality in Southeast Asia but are
      unlikely to transform TB control unless they are deployed actively and in the
      private sector. 

PMID- 24100954
TI  - The impact of illness on social networks: implications for transmission and
      control of influenza.
AB  - We expect social networks to change as a result of illness, but social contact
      data are generally collected from healthy persons. Here we quantified the impact
      of influenza-like illness on social mixing patterns. We analyzed the contact
      patterns of persons from England measured when they were symptomatic with
      influenza-like illness during the 2009 A/H1N1pdm influenza epidemic (2009-2010)
      and again 2 weeks later when they had recovered. Illness was associated with a
      reduction in the number of social contacts, particularly in settings outside the
      home, reducing the reproduction number to about one-quarter of the value it would
      otherwise have taken. We also observed a change in the age distribution of
      contacts. By comparing the expected age distribution of cases resulting from
      transmission by (a)symptomatic persons with incidence data, we estimated the
      contribution of both groups to transmission. Using this, we calculated the
      fraction of transmission resulting from (a)symptomatic persons, assuming equal
      duration of infectiousness. We estimated that 66% of transmission was
      attributable to persons with symptomatic disease (95% confidence interval: 0.23,
      1.00). This has important implications for control: Treating symptomatic persons
      with antiviral agents or encouraging home isolation would be expected to have a
      major impact on transmission, particularly since the reproduction number for this
      strain was low. 

PMID- 24100955
TI  - The potential impact of routine immunization with inactivated poliovirus vaccine
      on wild-type or vaccine-derived poliovirus outbreaks in a posteradication
      setting.
AB  - The "endgame" for worldwide poliomyelitis eradication will entail eventual
      cessation of the use of oral poliovirus vaccine (OPV) in all countries to prevent
      the reintroduction of vaccine-derived polioviruses--exposing some populations to
      an unprecedented, albeit low, risk of poliovirus outbreaks. Inactivated
      poliovirus vaccine (IPV) is likely to play a large part in post--OPV management
      of poliovirus risks by reducing the consequences of any reintroduction of
      poliovirus. In this article, we examine the impact IPV would have on an outbreak
      in a partially susceptible population after OPV cessation, using a mathematical
      model of poliovirus transmission with a realistic natural history and case
      reporting. We explore a range of assumptions about the impact of IPV on an
      individual's infectiousness, given the lack of knowledge about this parameter. We
      show that routine use of IPV is beneficial under most conditions, increasing the
      chance of fadeout and reducing the expected prevalence of infection at the time
      of detection. The duration of "silent" poliovirus circulation prior to detection
      lengthens with increasing coverage of IPV, although this only increases the
      expected prevalence of infection at the time of the OPV response if IPV has a
      very limited impact on infectiousness. Overall, the model predicts that routine
      use of IPV will be advantageous for the posteradication management of poliovirus.

PMID- 24100956
TI  - Validation of pediatric diabetes case identification approaches for diagnosed
      cases by using information in the electronic health records of a large integrated
      managed health care organization.
AB  - We explored the utility of different algorithms for diabetes case identification
      by using electronic health records. Inpatient and outpatient diagnosis codes, as
      well as data on laboratory results and dispensing of antidiabetic medications
      were extracted from electronic health records of Kaiser Permanente Southern
      California members who were less than 20 years of age in 2009. Diabetes cases
      were ascertained by using the SEARCH for Diabetes in Youth Study protocol and
      comprised the "gold standard." Sensitivity, specificity, positive and negative
      predictive values, accuracy, and the area under the receiver operating
      characteristic curve (AUC) were compared in 1,000 bootstrapped samples. Based on
      data from 792,992 youth, of whom 1,568 had diabetes (77.2%, type 1 diabetes;
      22.2%, type 2 diabetes; 0.6%, other), case identification accuracy was highest in
      75% of bootstrapped samples for those who had 1 or more outpatient diabetes
      diagnoses or 1 or more insulin prescriptions (sensitivity, 95.9%; positive
      predictive value, 95.5%; AUC, 97.9%) and in 25% of samples for those who had 2 or
      more outpatient diabetes diagnoses and 1 or more antidiabetic medications
      (sensitivity, 92.4%; positive predictive value, 98.4%; AUC, 96.2%). Having 1 or
      more outpatient type 1 diabetes diagnoses (International Classification of
      Diseases, Ninth Revision, Clinical Modification, code 250.x1 or 250.x3) had the
      highest accuracy (94.4%) and AUC (94.1%) for type 1 diabetes; the absence of type
      1 diabetes diagnosis had the highest accuracy (93.8%) and AUC (93.6%) for
      identifying type 2 diabetes. Information in the electronic health records from
      managed health care organizations provides an efficient and cost-effective source
      of data for childhood diabetes surveillance.

PMID- 24100957
TI  - Assessing the feasibility and sample quality of a national random-digit dialing
      cellular phone survey of young adults.
AB  - The majority of adults aged 18-34 years have only cellular phones, making random
      digit dialing of landline telephones an obsolete methodology for surveillance of
      this population. However, 95% of this group has cellular phones. This article
      reports on the 2011 National Young Adult Health Survey (NYAHS), a pilot study
      conducted in the 50 US states and Washington, DC, that used random-digit dialing
      of cellular phones and benchmarked this methodology against that of the 2011
      Behavioral Risk Factor Surveillance System (BRFSS). Comparisons of the
      demographic distributions of subjects in the NYAHS and BRFSS (aged 18-34 years)
      with US Census data revealed adequate reach for all demographic subgroups. After
      adjustment for design factors, the mean absolute deviations across demographic
      groups were 3 percentage points for the NYAHS and 2.8 percentage points for the
      BRFSS, nationally, and were comparable for each census region. Two-sided z tests
      comparing cigarette smoking prevalence revealed no significant differences
      between NYAHS and BRFSS participants overall or by subgroups. The design effects
      of the sampling weight were 2.09 for the NYAHS and 3.26 for the BRFSS. Response
      rates for the NYAHS and BRFSS cellular phone sampling frames were comparable. Our
      assessment of the NYAHS methodology found that random-digit dialing of cellular
      phones is a feasible methodology for surveillance of young adults.

PMID- 24100958
TI  - Peroneal flap in hypopharyngeal reconstruction.
AB  - BACKGROUND: Hypopharyngeal reconstruction is a complex and challenging task
      because the goal of the reconstruction is not only defect filling but also
      restoring functions such as swallowing and speech. In this article, we present a
      novel approach of using peroneal flaps in hypopharyngeal reconstructions.
      METHODS: Between 1997 and 2011, 14 peroneal flaps were used to reconstruct the
      hypopharynx of 13 patients. We retrospectively reviewed all the medical records
      from those surgeries, searching for either short-term postoperative complications
      or long-term follow-up morbidity, and researched relevant articles for
      comparisons with other types of flaps. RESULTS: Of the 14 peroneal flaps, five
      were applied in tubed form for a circumferential defect. The remaining nine
      peroneal flaps were applied in the form of a patch for a noncircumferential
      defect. None of the 14 flaps underwent flap loss. The rates of stenosis and
      fistula formation were 7.1 and 14.3 %, respectively. The average postoperative
      hospital stay was 20.2 days. Of 13 patients, nine were able to resume at least a
      soft diet after the reconstruction. Only one patient remained on nasogastric
      feeding through the 6-month follow-up period. None of the patients experienced
      significant complications. CONCLUSIONS: A peroneal flap reconstruction has
      comparable postoperative complications and donor site morbidity and should be
      considered as a viable option for hypopharyngeal reconstruction.

PMID- 24100959
TI  - Mucinous tumor of the appendix with limited peritoneal spread: is there a role
      for expectant observation?
AB  - BACKGROUND: Cytoreductive surgery (CRS) and hyperthermic intraperitoneal
      chemotherapy (HIPEC) is now the standard management for mucinous tumors of
      appendiceal origin at many centers. We examined the role of expectant observation
      (EO) in patients who had undergone an initial resection at the time of referral
      to our center and who had limited residual disease. METHODS: We performed a
      retrospective review of patients referred to Mount Sinai/Princess Margaret
      Hospitals, Toronto, for consideration of surgical management of peritoneal
      malignancy between January 1998 and December 2009. One hundred and three patients
      with primary mucinous appendiceal malignancy were identified. EO, consisting of
      regularly scheduled imaging and clinical review, was selected for asymptomatic
      patients with low-grade tumor and no/limited disease on imaging. Overall survival
      (OS) and progression-free survival (PFS) were determined. RESULTS: Management
      consisted of supportive care in 7 patients, systemic chemotherapy in 7, referral
      for CRS with HIPEC in 8, CRS without HIPEC at our center in 51, and EO in 30. In
      the CRS group, 5-year OS was 74 % and PFS was 56 %; both OS and PFS were
      predicted by extent of residual disease after cytoreduction (p = 0.014 and p =
      0.011, respectively). In the EO group, 5-year OS and PFS were 95 and 82 %,
      respectively. Two patients in the EO group subsequently underwent CRS for
      progression on imaging. CONCLUSIONS: In well-selected patients who have undergone
      initial resection for low-grade mucinous tumor of the appendix with limited
      peritoneal spread, a formal program of observation can result in excellent 5-year
      OS and PFS. Longer-term follow-up will help define the benefits and risks of this
      approach.

PMID- 24100960
TI  - Is there an optimal surgery time after endoscopic resection in early gastric
      cancer?
AB  - BACKGROUND: The patients with early gastric cancer who have undergone incomplete
      endoscopic resection (ER) generally need additional surgery because of the
      possibility of lymph node metastasis. The aim of study was to evaluate the
      optimal time interval from ER to additive surgery by evaluating the effect of
      time interval on the surgical and oncological outcomes. METHODS: We analyzed 154
      patients who underwent additive gastrectomy after incomplete ER at Severance and
      Gangnam Severance Hospitals. The time interval point, at which operative time and
      estimated intraoperative blood loss (EBL) of the earlier operation group and the
      later operation group showed the greatest disparities, was evaluated. The
      patients were divided into 2 groups according to the time interval point, as the
      earlier operation group (group A) and the later operation group (group B). We
      retrospectively evaluated the clinicopathological characteristics and surgical
      and oncological outcomes. RESULTS: The greatest difference between operative time
      and EBL was in the groups who underwent operation before and after 29 days. Of
      the 154 patients, 78 were in group A (<=29 days) and 76 in group B (>29 days).
      There were no differences in the clinicopathological characteristics and
      oncological outcomes except for tumor size. The operative time and EBL were
      significantly longer and more in group A compared with group B. CONCLUSIONS: The
      time interval between ER and additive surgery is associated with surgical
      outcomes. Additive surgery at about 1 month after ER may be optimal for better
      surgical outcomes without affecting the oncological outcomes.

PMID- 24100961
TI  - Prophylactic central neck dissection increases the cost of thyroid cancer care.

PMID- 24100962
TI  - Impact of neoadjuvant chemoradiotherapy on postoperative course after curative
      intent transthoracic esophagectomy in esophageal cancer patients.
AB  - BACKGROUND: Neoadjuvant chemoradiotherapy (CRT) improves locoregional control and
      overall survival in esophageal cancer patients. Although adverse events are
      relatively low during neoadjuvant CRT, severe postoperative adverse effects may
      occur, leading to morbidity and even mortality. We investigated the impact of a
      more frequently used neoadjuvant CRT regimen of 41.4 Gy/5 weeks radiotherapy with
      concurrent carboplatin and paclitaxel (CROSS schedule) on the postoperative
      course. METHODS: Between 2006 and 2012, a total of 96 esophageal cancer patients
      (staged cT1N+/T2-4a/N0-3 and M0) were treated according to the above neoadjuvant
      scheme. To reduce bias in this single-center study, we performed a propensity
      score-matched analysis with patients who underwent surgery alone (n = 230) from a
      prospectively maintained database (n = 326). RESULTS: Baseline characteristics
      between both groups were equally distributed in the matched cohort. In the
      neoadjuvant treated group, significantly more patients were diagnosed with
      pneumonia (27.1 vs. 51.0%; p = 0.001), pleural effusion (12.5 vs. 24.0%; p =
      0.040), and arrhythmia (20.4 vs. 34.4%; p = 0.008). In addition, in the
      multivariate analysis, neoadjuvant CRT was significantly associated with an
      increased risk of pneumonia (p = 0.001, odds ratio 2.896), pleural effusion (p =
      0.041, odds ratio 2.268), and arrhythmia (p = 0.023, odds ratio 2.215). Despite
      these outcomes, no differences were detected in duration of intensive care unit
      or hospital stay. Short-term mortality did not differ between both groups.
      CONCLUSIONS: We observed an increase of cardiopulmonary complications in the
      neoadjuvant CRT group, without any effect on hospital or intensive care unit stay
      and mortality. Further research is warranted on the limitation of chemoradiation
      induced cardiopulmonary toxicity.

PMID- 24100963
TI  - Indicators of central fever in the neurologic intensive care unit.
AB  - IMPORTANCE: Fever is common in critically ill neurologic patients. Knowledge of
      the indicators of central fever may allow greater antibiotic stewardship in this
      era of rapidly developing super-resistant microorganisms. OBJECTIVE: To develop a
      model to differentiate central from infectious fever in critically ill neurologic
      patients with fever of an undetermined cause. DESIGN, SETTING, AND PARTICIPANTS:
      Retrospective data collection from January 1, 2006, through December 31, 2010, at
      a 20-bed neurologic intensive care unit of a large teaching hospital. Consecutive
      patients 18 years and older admitted for 48 hours or longer with a core body
      temperature higher than 38.3  degrees C on at least 1 measurement for 2
      consecutive days. Patients with alternative identified causes of noninfectious
      fever were excluded. In total, 526 patients were included in the final analysis.
      MAIN OUTCOMES AND MEASURES: Percentage incidence and odds ratios of variables
      associated with central fever. Fever was classified as infectious if there was
      culture growth of a pathogenic species or documented clinical diagnosis of
      infection treated with antibiotics. Remaining patients were considered to have
      central fever. Continuous fever lasting longer than 6 hours for 2 or more
      consecutive days was considered persistent. RESULTS Fever was central in 246
      patients (46.8%). Patients with infectious fever were older (mean, 57.4 vs 53.5
      years; P = .01) and had a longer length of stay in the neurologic intensive care
      unit (mean, 12.1 vs 8.8 days; P < .001). Central fever was more likely to occur
      within 72 hours of admission to the neurologic intensive care unit (76.4% vs
      60.7%; P < .001) and tended to be persistent (26.4% vs 18.6%; P = .04). Blood
      transfusion (odds ratio [OR], 3.06; 95% CI, 1.63-5.76); absence of infiltrate on
      chest x-ray (3.02; 1.81-5.05); diagnosis of subarachnoid hemorrhage,
      intraventricular hemorrhage, or tumor (6.33; 3.72-10.77); and onset of fever
      within 72 hours of hospital admission (2.20; 1.23-3.94) were independent
      predictors of central fever on multivariable analysis. The combination of
      negative cultures; absence of infiltrate on chest radiographs; diagnosis of
      subarachnoid hemorrhage, intraventricular hemorrhage, or tumor; and onset of
      fever within 72 hours of admission predicted central fever with a probability of
      .90. CONCLUSIONS AND RELEVANCE: We provide a reliable model to differentiate
      central fever from infectious fever in critically ill neurologic patients,
      allowing clinicians to select patients in whom antibiotics may be safely
      discontinued despite ongoing fever.

PMID- 24100965
TI  - Animal research: a balancing act.

PMID- 24100964
TI  - VolRoverN: enhancing surface and volumetric reconstruction for realistic
      dynamical simulation of cellular and subcellular function.
AB  - Establishing meaningful relationships between cellular structure and function
      requires accurate morphological reconstructions. In particular, there is an unmet
      need for high quality surface reconstructions to model subcellular and synaptic
      interactions among neurons and glia at nanometer resolution. We address this need
      with VolRoverN, a software package that produces accurate, efficient, and
      automated 3D surface reconstructions from stacked 2D contour tracings. While many
      techniques and tools have been developed in the past for 3D visualization of
      cellular structure, the reconstructions from VolRoverN meet specific quality
      criteria that are important for dynamical simulations. These criteria include
      manifoldness, water-tightness, lack of self- and object-object-intersections, and
      geometric accuracy. These enhanced surface reconstructions are readily extensible
      to any cell type and are used here on spiny dendrites with complex morphology and
      axons from mature rat hippocampal area CA1. Both spatially realistic surface
      reconstructions and reduced skeletonizations are produced and formatted by
      VolRoverN for easy input into analysis software packages for neurophysiological
      simulations at multiple spatial and temporal scales ranging from ion electro
      diffusion to electrical cable models. 

PMID- 24100966
TI  - Polypill improves adherence but fails to win all scientists' hearts.

PMID- 24100967
TI  - First IL-6-blocking drug nears approval for rare blood disorder.

PMID- 24100968
TI  - Syrian gas attack reinforces need for better anti-sarin drugs.

PMID- 24100969
TI  - Caution urged over the FDA's new breakthrough designation.

PMID- 24100971
TI  - Straight talk with...Daniel Levy. Interviewed by Elie Dolgin.
AB  - The Framingham Heart Study (FHS) has long been a beacon of biomedical research,
      yielding landmark findings on everything from the links between elevated blood
      pressure and stroke to the genetic risk factors underlying cardiac arrhythmias.
      Now, the fabled 65-year-long study of cardiovascular disease is the beacon of a
      more modern trend in science: tight budgets. Thanks to the automatic cuts in US
      government spending known as sequestration, the approximately $9-million-per-year
      contract the FHS receives from the US National Heart, Lung, and Blood Institute
      (NHLBI) was reduced by $4 million on 1 August. The renewal of the contract,
      scheduled for 2015, is expected to run for only two or three years, instead of
      the usual seven as it has been in the past. And next month, the most visible
      effects of the cuts will take hold, when 19 layoffs (out of a total of 90 total
      staff members) go into effect. Overseeing the budget-related turbulence is Daniel
      Levy, a medical officer at the NHLBI who joined the FHS nearly 30 years ago and
      has served as the study's director since 1994. Elie Dolgin met with Levy in
      Framingham, on the outskirts of Boston, to discuss how he's taking the new
      funding realities to heart.

PMID- 24100974
TI  - Finding the right chemistry.

PMID- 24100975
TI  - Animal experiments deserve a place on drug labels.

PMID- 24100977
TI  - Therapeutically reeducating macrophages to treat GBM.
AB  - Glioblastoma multiforme (GBM) is the most common type of aggressive malignant
      brain cancer. The current lack of successful therapeutics means that this disease
      has a dismal prognosis. However, a new study in mice offers hope for patients
      with GBM by demonstrating the efficacy of a novel drug that targets GBM
      associated macrophages (pages 1264-1272).

PMID- 24100978
TI  - To B or not to B--that is the question for myocardial infarction.
AB  - After myocardial infarction (MI), circulating B cells produce the chemokine Ccl7,
      which mobilizes inflammatory monocytes from the bone marrow into the blood, after
      which they are then recruited to the injured heart, a new study shows. B cell
      depletion after MI limits myocardial injury and improves heart function,
      suggesting a new approach for the management of acute MI (pages 1273-1280).

PMID- 24100979
TI  - NKT cells: the smoking gun in fungal-induced asthma?
AB  - Aspergillus fumigatus is a fungus that is associated with a severe form of
      asthma, although the precise immunological basis for this disease is unclear. A
      new study in mice shows that natural killer T (NKT) cells are crucial for
      progression of A. fumigatus-induced asthma and also identifies a glycolipid
      antigen from this fungus that seems to drive this NKT cell-mediated inflammatory
      response (pages 1297-1304).

PMID- 24100980
TI  - Akt2 relaxes podocytes in chronic kidney disease.
AB  - A signaling cascade is activated in podocytes to induce survival and cope with
      stress during advanced glomerular disease, a new study shows. The findings may
      also explain why the immunosuppressor sirolimus, an inhibitor of this pathway,
      can cause proteinuria in a subset of patients with chronic kidney disease (pages
      1288-1296).

PMID- 24100981
TI  - Semagacestat's fall: where next for AD therapies?

PMID- 24100982
TI  - Metabolic disease puts up a fight: are diet and exercise helpful for the heart?

PMID- 24100983
TI  - Metabolic disease puts up a fight: microbes, metabolism and medications.

PMID- 24100991
TI  - Juxtapositions in Trafalgar Square: tip-offs to creativity in art and science.

PMID- 24100992
TI  - A molecular machine for neurotransmitter release: synaptotagmin and beyond.

PMID- 24100993
TI  - In search of the molecular mechanism of intracellular membrane fusion and
      neurotransmitter release.

PMID- 24100994
TI  - The multichannel cochlear implant for severe-to-profound hearing loss.

PMID- 24100995
TI  - The importance of being flexible.

PMID- 24100996
TI  - Toward better representations of sound with cochlear implants.

PMID- 24100997
TI  - An interview with Bill and Melinda Gates. Interviewed by Claire Pomeroy.
AB  - Bill and Melinda Gates have led a profound transformation in the way we view the
      world's most pressing health concerns, looking for effective ways to improve the
      lives of millions of people. Claire Pomeroy, president of the Albert and Mary
      Lasker Foundation, spoke with them about their current concerns and plans to
      advance their agenda.

PMID- 24100999
TI  - Etoposide induces apoptosis via the mitochondrial- and caspase-dependent pathways
      and in non-cancer stem cells in Panc-1 pancreatic cancer cells.
AB  - Pancreatic cancer is a highly aggressive malignant tumor. In the present study,
      we performed several methods, including CCK-8 assay, immunofluorescence
      technique, western blotting and flow cytometry, to determine the effects of VP16
      (etoposide) on Panc-1 pancreatic cancer cells. The results demonstrated that VP16
      inhibited the growth of and induced apoptosis in Panc-1 cells. Western blot
      analysis showed that VP16 inhibited the expression of Bcl-2 and enhanced the
      expression of Bax, caspases-3 and -9, cytochrome c and PARP. Notably, a strong
      inhibitory effect of VP16 on Panc-1 cells mainly occurred in non-CSCs. These data
      provide a new strategy for the therapy of pancreatic cancer.

PMID- 24101000
TI  - Robotic esophagectomy: new era of surgery.
AB  - Esophagectomy is a surgical operation which requires technical expertise to
      decrease the morbidity and mortality frequently associated with this advance
      procedure. Various minimally invasive esophagectomy techniques have been
      developed to decrease the negative impact of esophageal resection. Recently,
      robotic assisted esophagectomies have been described with a wide variety in
      technique and outcome disparity. This article is a summation review of the
      current literature regarding the various techniques and surgical outcomes of
      robotic assisted esophagectomies. 

PMID- 24101001
TI  - Single-site robotic cholecystectomy (SSRC): an initial review of safety and
      feasibility.
AB  - AIM: This report comprehensively reviews the findings from initial experiences
      with single-site robotic cholecystectomy (SSRC) across the world, and reports the
      feasibility of this new approach and novel platform. It attempts to be impartial
      in evaluating this novel robotic platform and approach. METHODS: A search
      utilizing MEDLINE(r)/PubMed(r) and Google Scholar was undertaken to identify
      articles about SSRC. Eleven articles met our criteria and were reviewed. Data
      collected included: patient demographic, preoperative, intraoperative, and
      postoperative data. Data are presented as weighted means+/-pooled standard
      deviations. RESULTS: Age and BMI was 46+/-13.1 years and 26+/-4.2 kg/m2,
      respectively. Operative time was 80+/-24.1 minutes; robotic console time was 38+/
      16.9 minutes; and docking time was 7+/-3.1 minutes. Blood loss ranged from 0-150
      mL. Ninety-eight percent of SSRC undertaken were completed robotically without
      the addition of other trocars/incisions, 2% of operations had additional trocars
      added, and three operations (<1%) were converted to "open". Postoperative
      hospital stay was 26 hours. Pain ratings, determined 2-3 weeks postoperatively,
      ranged from 0-2 on a Likert scale. CONCLUSION: This study serves as an overall
      analysis and review of SSRC. Existing reports of initial experiences with SSRC
      documents the operation is safe, feasible, and easily learned by surgeons from a
      broad spectrum of geographic areas. However, a detailed cost analysis is
      necessary in order to determine what the future holds for this novel approach.

PMID- 24100998
TI  - Brown and beige fat: development, function and therapeutic potential.
AB  - Adipose tissue, best known for its role in fat storage, can also suppress weight
      gain and metabolic disease through the action of specialized, heat-producing
      adipocytes. Brown adipocytes are located in dedicated depots and express
      constitutively high levels of thermogenic genes, whereas inducible 'brown-like'
      adipocytes, also known as beige cells, develop in white fat in response to
      various activators. The activities of brown and beige fat cells reduce metabolic
      disease, including obesity, in mice and correlate with leanness in humans. Many
      genes and pathways that regulate brown and beige adipocyte biology have now been
      identified, providing a variety of promising therapeutic targets for metabolic
      disease. 

PMID- 24101002
TI  - Robotic colectomy: is it necessary?
AB  - More than 20 years ago the introduction of laparoscopic surgery represented a
      paradigm shift in the management of colorectal cancer. In most recent years
      robotic surgery is becoming a viable alternative to laparoscopic and traditional
      open surgery. The major clear advantages of robotic surgery in comparison with
      laparoscopy are the lower conversion to open surgery rates and the shorter
      learning curve. However, the role of robotics in colorectal surgery is still
      largely undefined and different with respect to its application in abdominal
      versus pelvic surgery. As for colon cancer there are emerging data that
      laparoscopic and robotic surgery have the same advantages in terms of faster
      recovery, although robotic-assisted colectomy is associated with costs increase
      of care without providing clear reduction in overall morbidity or length of stay.
      Long-term outcomes for laparoscopic versus robotic colonic resections remain
      still largely undetermined and randomized controlled clinical trials are required
      to establish a possible difference in outcomes. Interesting issues for the
      educational aspects are associated with robotic surgery, as the double console
      allows the resident to take part actively at the surgical procedure since the
      beginning of his surgical experience. 

PMID- 24101003
TI  - Robotic rectal surgery: what are the benefits?
AB  - Robotic rectal surgery is not a rare event for colorectal surgeons any more. Even
      patients with colorectal diseases obtain information through the mass media and
      are asking surgeons about robotic surgery. Since laparoscopic rectal surgery has
      proved to have some benefits compared to open rectal surgery, many surgeons
      became interested in robotic rectal surgery. Some of them have reported the
      advantages and disadvantages of robotic rectal surgery over the last decade. This
      review will report on the outcomes of robotic rectal surgery. Robotic rectal
      surgery requires a longer operation time than laparoscopic or open surgery, but
      many authors reduced the gap as they were accustomed to the robotic system and
      used various additional techniques. The high cost for purchasing and maintaining
      the robotic system is still a problem, though. However, except for this reason,
      robotic rectal surgery shows comparable and even superior results in some
      parameters than laparoscopic or open surgery. They include pathologic and
      functional outcomes as well as short-term outcomes such as complication rates,
      length of hospital stay, time to recover normal bowel function or first flatus,
      time to start diet, and postoperative pain. Moreover, studies on oncologic
      outcomes show acceptable results. Robotic rectal surgery is safe and feasible and
      has a number of benefits. Therefore, it can be an alternative option to
      conventional laparoscopic and open surgery with strict indications. 

PMID- 24101004
TI  - Robot-assisted laparoscopic colorectal surgery.
AB  - Colorectal cancer is one of the most common malignancies seen in developed
      countries. Its current treatment is based on a multidisciplinary approach
      entailing surgery, chemotherapy and radiotherapy. Surgery can be performed with
      open and minimal invasive methods. Single incision laparoscopic surgery (SILS),
      natural orifice transluminal endoscopic surgery (NOTES) and robot assisted
      laparoscopic surgery (RALS) are the final points to be reached in minimally
      invasive surgery. The first robotic colorectal surgical intervention was
      performed in 2001 after getting the FDA approval for the da Vinci surgical system
      in intraabdominal surgery, and since then, its use in this field gradually
      increased. Compared to open surgery, the advantage and superiority of robotic
      surgery, especially in narrow areas such as the pelvis, has been shown in many
      studies. It is a safe and feasible method. Although there are many existing
      studies about minimally invasive surgery, more randomized studies with larger
      case numbers should be carried out in order to establish the favorable
      oncological and functional outcomes of robotic surgery in addition to its
      obviously observed advantages. 

PMID- 24101005
TI  - Robotic hepatobiliary surgery: update on the current status.
AB  - An update on the current status of robotic hepatobiliary surgery based on a
      review of the available literature. A literature search was performed using the
      PubMed database with search phrases "robotic hepatectomy", "robotic liver
      resection", "robotic liver surgery", "robotic hepatobiliary surgery", and
      "robotic biliary reconstruction". We selected articles with high volume case
      series or case controlled series. As a result of our literature search we will
      focus on the 9 major articles on robotic liver resection (RLR) with 235 patients
      undergoing RLR for a total of 244 liver resections. In addition a brief update on
      robotic biliary reconstruction will also be presented based on the above articles
      and recent review articles. Indications for robotic liver resection included both
      benign (N.=72, 29.5%) and malignant disease (N.=172, 70.5%). The most common
      indication was colorectal liver metastasis (N.=87, 50.6%) and hepatocellular
      carcinoma (N.=57, 33%). The most common type of resection was subsegmental
      (N.=55, 22.5%), with a significant number of major hepatectomies (N.=80, 32.8%).
      Overall conversion rate was 7.8%, with majority converted to open (N.=18) and one
      converted to hand assisted. The overall complication rate was 11.8% (N.=29). No
      perioperative mortality was reported. Preliminary results show that robotic
      assisted laparoscopic hepatobiliary surgery has materialized as a new technique
      that combines the advantages of laparoscopy with the dissection, suturing and
      articulation of robotics. This more closely approximates open surgery. The
      preliminary data demonstrates that RLR can be applied in major hepatobiliary
      centers safely. Future comparative studies are needed to determine if this is of
      significant benefit over current open techniques. 

PMID- 24101006
TI  - Robotic distal pancreatectomy: a valid option?
AB  - Although reported in the literature, conventional laparoscopic approach for
      distal pancreatectomy is still lacking widespread acceptance. This might be due
      to two-dimensional vision and decreased range of motion to reach and safely
      dissect this highly vascularized retroperitoneal organ by laparoscopy. However,
      interest in minimally invasive access is growing ever since and the robotic
      system could certainly help overcome limitations of the laparoscopic approach in
      the challenging domain of pancreatic resection, notably in distal pancreatectomy.
      Robotic distal pancreatectomy with and without spleen preservation has been
      reported with encouraging outcomes for benign and borderline malignant disease.
      As a result of upgraded endowristed manipulation and three-dimensional
      visualization, improved outcome might be expected with the launch of the robotic
      system in the procedure of distal pancreatectomy. Our aim was thus to extensively
      review the current literature of robot-assisted surgery for distal pancreatectomy
      and to evaluate advantages and possible limitations of the robotic approach. 

PMID- 24101007
TI  - Robot assisted laparoscopic prostatectomy in 2013.
AB  - Robot assisted laparoscopic prostatectomy has surpassed open radical
      prostatectomy as the most common surgical approach for radical prostatectomy in
      the United States. In this article we briefly describe the evolution of this
      minimally invasive technique. The current diagnostic approaches of
      multiparametric magnetic resonance imaging and fusion biopsy used in preoperative
      workup of the patients are discussed, followed by a description of risk
      stratified a thermal nerve sparing approach with total anatomical reconstruction.
      Finally we present a critical appraisal of the published oncological, continence
      and potency outcomes.

PMID- 24101008
TI  - Standardization of laparoscopic left hemicolectomy: a single-center experience of
      484 cases.
AB  - AIM: Laparoscopic surgery has become recognized as an established technique for
      colon diseases and many different surgical techniques have been described. The
      aim of our study is to show the results of a single institution where a
      standardized operative and perioperative procedure for laparoscopic left
      hemicolectomy (LLH) has been used. METHODS: Between January 2005 and April 2011,
      484 patients underwent LLH for colon diseases. Data collected included age,
      indication for surgery, ASA class, body mass index, operating time, intra and
      post-operative complications, conversion rate, length of hospital stay, tumor
      stage, number of lymph nodes harvested, mortality, and a 30-day readmission rate.
      RESULTS: We found 299 cancer, 29 large dysplastic polyps and 156 complicated
      diverticular diseases. Average operation time was 120 minutes. The average
      hospital stay was 5.7 days. In the cancer group, the average number of lymph
      nodes harvested was 12.7. The intraoperative and early postoperative
      complications were 3.3% and 10.7 % respectively. The conversion rate was 3.7%.
      The 30-day readmission rate was 3%. The 30-day mortality rate was 0.4%.
      CONCLUSION. The standardization of the LLH technique might reduce the technical
      difficulties and complications. Its potential benefits include the
      standardization of surgical instrument sets, the definition of benchmarks for
      conversion before making any inappropriate investment in time and equipment, low
      rates of complications and readmission rate.

PMID- 24101009
TI  - Omitting of bougie appears to be safe for the performance of the fundal wrap at
      laparoscopic Nissen fundoplication.
AB  - AIM: Some operative techniques in fundoplication seem to increase the incidence
      of obstructive symptoms. Some authors believe that using intraesophageal bougie
      and preparing a short and floppy valve in laparoscopic Nissen fundoplication will
      help to decrease any possible tight crus repair and wrap and so it is effective
      to decrease the prevalence of postoperative dysphagia. The aim of this study is
      to show that there is no absolute benefit of routine insertion of a bougie during
      laparoscopic Nissen fundoplication in relation to post-operative dysphagia.
      METHODS: All patients who underwent laparoscopic Nissen fundoplication by a
      single surgeon between January 2001 and August 2011 were reviewed
      retrospectively. Esophageal bougie intubation was performed in none of the 154
      patients. The operation technique, the duration of the operation, hospital stay
      and the improvement of the symptoms were assessed. The patients who had
      esophagitis with Barrett's esophagus and who had hiatal hernia that could not get
      benefit from medical therapy, were selected for the surgery. Laparoscopic Nissen
      fundoplication with cruroraphy were done in all patients. RESULTS: Ninety-six of
      the patients were female and 58 were male. The mean symptom duration was 3.6+/
      0.6 years. The only complication was dysphagia. In eighth week, dysphagia
      resolved in all patients. CONCLUSION: Laparoscopic Nissen fundoplication can be
      safely performed without the routine use of an esophageal bougie and it does not
      increase the postoperative dysphagia rate.

PMID- 24101010
TI  - Patient with coronary stents needs surgery: what to do?

PMID- 24101011
TI  - Postoperative chyle leak after major pancreatic resections in patients who
      receive enteral feed: risk factors and management options.
AB  - BACKGROUND: Chyle leak complicates 1.3-10.8 % of pancreatic resections. Universal
      use of parenteral nutrition following pancreatic resection may reduce the
      incidence of chyle leak. However, this denies the majority of patients who do not
      develop chyle leak the benefits of enteral nutrition (EN). The present study
      aimed to identify risk factors for chyle leak following pancreatic resection
      within a single institution where EN was used universally. METHODS: All patients
      who underwent pancreatic resection between January 2007 and December 2010 were
      identified retrospectively. The patients had been treated according to a common
      unit protocol of enteral feeding; those developing chyle leak were switched to a
      medium-chain triglyceride (MCT) regimen. Clinical progress and recovery after
      surgery was evaluated. Multivariate analysis was performed to identify factors
      associated with chyle leak. RESULTS: A total of 245 patients underwent major
      pancreatic resection (231 pancreatoduodenectomy, 14 total pancreatectomy). Chyle
      leak complicated 40 cases (16.3 %). After multivariate analysis, both extensive
      lymphadenectomy (P = 0.002) and postoperative portal/mesenteric venous thrombosis
      (PVT) (P = 0.009) were independently linked with a higher incidence of chyle
      leak. The development of chyle leak was not associated with poorer survival or
      prolonged duration of hospital stay. It was associated with a significantly
      increased duration of abdominal drainage and reduced likelihood of early hospital
      discharge (P = 0.026). CONCLUSIONS: Universal use of enteral feeding is
      associated with a high rate of chyle leak following pancreatic resection.
      Patients undergoing extensive lymphadenectomy or those who develop PVT
      postoperatively are at increased risk. Development of chyle leak was not
      associated with additional morbidity or mortality following implementation of an
      MCT regimen. The implication is that reactive management of chyle leak with
      conversion to a MCT predominant diet is safe.

PMID- 24101013
TI  - The rate and mortality of postoperative venous thromboembolism of moderate risk
      surgery in Asian patients without thrombo-prophylaxis: systematic review with
      meta-analysis.
AB  - BACKGROUND: The general gynecologic and neurologic surgeries are regard as
      carrying moderate risk for postoperative venous thromboembolism (VTE). This
      review analyzed the postoperative VTE rate of these surgeries in Asia. METHODS:
      Inclusion criteria were: prospective study; deep vein thrombosis (DVT) diagnosed
      by venography, ultrasonography, or radionucleotide scan; and no
      thromboprophylaxis. The pooled proportion was back calculated from Freeman-Tukey
      variant transformation, using a random effect model. RESULTS: Medline, EMBASE,
      Cochrane Library, and KoreaMed were searched. Fourteen studies (total population
      of 1,625) published from 1974 to 2008 were included. In general surgery, the
      pooled rate of all-sites proximal, isolated distal DVT was 13.4, 2.1, and 11.8 %
      (radionucleotide scan). The cancer patients carried a higher all-sites DVT rate
      (19.7 % radionucleotide scan and 17.4 % ultrasound). Gynecologic and neurologic
      surgery had 3.1 % (ultrasound) and 3.8 % (radionucleotide scan) all-sites DVT
      rate. For general, gynecologic, and neurologic patients, the pooled rates of
      symptomatic DVT were 1.5, 0.2, and 1.0 % respectively. The pooled rate of
      symptomatic pulmonary embolism (PE) was 0.4 % for general surgery. No patients
      died from PE (pooled rate 0.2 %); however, a single PE death was reported in the
      excluded study. CONCLUSIONS: Postoperative symptomatic VTE was relatively low in
      Asia. Further study is required to stratify VTE risk and the need for
      thromboprophylaxis in individual patients.

PMID- 24101012
TI  - Time to readiness for discharge is a valid and reliable measure of short-term
      recovery after colorectal surgery.
AB  - BACKGROUND: Short-term recovery after colorectal surgery has been traditionally
      investigated through length of stay (LOS). However, this measure is influenced by
      several confounding factors. This study aimed to investigate the construct
      validity and reliability of assessing the time to achieve standardized discharge
      criteria (time to readiness for discharge, or TRD) as a measure of short-term
      recovery. In a secondary analysis, we compared sample size requirements for
      randomized controlled trials (RCTs) using TRD or LOS as outcome measures.
      METHODS: Seventy patients participated in the construct validity study and 21
      patients participated in the reliability study. TRD was defined as the number of
      days to achieve discharge criteria previously defined by consensus. Construct
      validity was investigated by testing six hypothesis based on the assumption that
      TRD measures short-term recovery. Reliability was calculated by comparing
      measures of TRD by two independent assessors. Variability estimates (standard
      deviations) of LOS and TRD were used for sample size calculations. RESULTS: Five
      of the six hypotheses were supported by the data (p < 0.05). Interobserver
      reliability was excellent (ICC2.1 = 0.99). Sample size estimations showed that
      RCTs using TRD as an outcome measure require approximately 23 % less participants
      compared to RCTs using LOS. CONCLUSIONS: The results of this research support the
      construct-validity and reliability of TRD as a measure of short-term recovery.
      Using TRD as an alternative to LOS may reduce sample size requirements in future
      RCTs.

PMID- 24101014
TI  - Motorised two-wheeler crash and helmets: injury patterns, severity, mortality and
      the consequence of gender bias.
AB  - BACKGROUND: India records the maximum number of deaths from motorised two-wheeler
      vehicle (MTV) accidents in the world with mandatory helmet laws for males but not
      females. This study was designed to investigate injury patterns, severity,
      mortality, and helmet usage among hospital admitted victims of a MTV crash with a
      paired subgroup analyses on female victims. METHODS: Hospital trauma registry
      from January 2011 to July 2012 for all adult victims of a MTV crash was analysed
      for outcomes of mortality, serious head injury, severe facial injury, and
      cervical spine injury while adjusting for age, gender, use of alcohol/drugs,
      injury severity score, and presence of shock by multivariable logistic regression
      model. Groups of helmeted victims (HV) and nonhelmeted victims (NHV) were
      identified. RESULTS: A total of 2,718 victims were included. HV suffered maximum
      injuries to the lower extremity (29.04 %) and had reduced adjusted odds of death
      (odds ratio (OR) 0.65; 95 % confidence interval (CI) 0.48-0.86), serious head
      injury (OR 0.34; CI 0.26-0.45), cervical spine injury (OR 0.74; CI 0.54-1.06),
      and serious facial injury (OR 0.87; CI 0.57-1.26) compared with NHV who suffered
      maximum injuries to the head (24.49 %). Compliance with helmet use was 52.91 and
      7.94 % among males and females respectively. A total of 224 pairs of male driver
      and female pillion involved in same MTV crash were identified, and the
      predominantly helmeted male had reduced odds of death (OR 0.44; CI 0.21-0.84) and
      severe head injury (OR 0.42; CI 0.24-0.72) compared with overwhelmingly
      nonhelmeted females. CONCLUSIONS: Helmet laws must be strictly enforced, and
      society should think about the cost being born by its fairer counterpart by the
      gender-based differential law.

PMID- 24101015
TI  - Biologic versus nonbiologic mesh in ventral hernia repair: a systematic review
      and meta-analysis.
AB  - BACKGROUND: The current standard of treatment for most ventral hernias is a mesh
      based repair. Little is known about the safety and efficacy of biologic versus
      nonbiologic grafts. A meta-analysis was performed to examine two primary
      outcomes: recurrence and wound complication rates. METHODS: Electronic databases
      and reference lists of relevant articles were systematically searched for all
      clinical trials and cohort studies published between January 1990 and January
      2012. A total of eight retrospective studies, with 1,229 patients, were included
      in the final analysis. RESULTS: Biologic grafts had significantly fewer
      infectious wound complications (p < 0.00001). However, the recurrence rates of
      biologic and nonbiologic mesh were not different. In subgroup analysis, there was
      no difference in recurrence rates and wound complications between human-derived
      and porcine-derived biologic grafts. CONCLUSIONS: Use of biologic mesh for
      ventral hernia repair results in less infectious wound complications but similar
      recurrence rates compared to nonbiologic mesh. This supports the application of
      biologic mesh for ventral hernia repair in high-risk patients or patients with a
      previous history of wound infection only when the significant additional cost of
      these materials can be justified and synthetic mesh is considered inappropriate.

PMID- 24101016
TI  - Immunological changes after minimally invasive or conventional esophageal
      resection for cancer: a randomized trial.
AB  - BACKGROUND: This study was performed as a substudy analysis of a randomized trial
      comparing conventional open esophagectomy [open surgical technique (OE)] by
      thoracotomy and laparotomy with minimally invasive esophagectomy [minimally
      invasive procedure (MIE)] by thoracoscopy and laparoscopy. This additional
      analysis focuses on the immunological changes and surgical stress response in
      these two randomized groups of a single center. METHODS: Patients with a
      resectable esophageal cancer were randomized to OE (n = 13) or MIE (n = 14). All
      patients received neoadjuvant chemoradiotherapy. The immunological response was
      measured by means of leukocyte counts, HLA-DR expression on monocytes, the acute
      phase response by means of C-reactive protein (CRP), interleukin-6 (IL-6), and
      interleukin-8 (IL-8), and the stress response was measured by cortisol, growth
      hormone, and prolactin. All parameters were determined at baseline
      (preoperatively) and 24, 72, 96, and 168 h postoperatively. RESULTS: Significant
      differences between the two groups were seen in favor of the MIE group with
      regard to leukocyte counts, IL-8, and prolactin at 168 h (1 week)
      postoperatively. For HLA-DR expression, IL-6, and CRP levels, there were no
      significant differences between the two groups, although there was a clear rise
      in levels upon operation in both groups. CONCLUSION: In this substudy of a
      randomized trial comparing minimally invasive and conventional open
      esophagectomies for cancer, significantly better preserved leukocyte counts and
      IL-8 levels were observed in the MIE group compared to the open group. Both
      findings can be related to fewer respiratory infections found postoperatively in
      the MIE group. Moreover, significant differences in the prolactin levels at 168 h
      after surgery imply that the stress response is better preserved in the MIE
      group. These findings indicate that less surgical trauma could lead to better
      preserved acute-phase and stress responses and fewer clinical manifestations of
      respiratory infections.

PMID- 24101018
TI  - Location of lymph node involvement in patients with esophageal adenocarcinoma
      predicts survival.
AB  - BACKGROUND: The location of positive lymph nodes has been abandoned in the
      seventh classification of the TNM staging system for esophageal adenocarcinoma.
      The present study evaluates whether distribution of involved nodes relative to
      the diaphragm in addition to TNM 7 further refines prediction. METHODS: Pathology
      reports of patients who underwent esophagectomy between 2000 and 2008 for
      adenocarcinoma of the esophagus were reviewed and staging was performed according
      to the seventh UICC-AJCC staging system. In addition, lymph node involvement of
      nodal stations above and below the diaphragm was investigated by endoscopic
      ultrasonography (EUS) in a separate cohort of patients who were scheduled for
      esophagectomy between 2008 and 2009 at two institutions. Survival was calculated
      by the Kaplan-Meier method, and multivariate analysis was performed with a Cox
      regression model. RESULTS: Some 327 patients who had undergone esophagectomy for
      cancer were included. Multivariate analysis revealed that patients with from
      three to six involved lymph nodes in the resection specimen on both sides of the
      diaphragm had a twofold higher chance of dying compared to patients with the same
      number of involved lymph nodes on one side of the diaphragm. EUS assessment of
      lymph node metastases relative to the diaphragm in 102 patients showed that nodal
      involvement on both sides of the diaphragm was associated with worse survival
      than when nodes on one side or no nodes are involved [HR (95 % CI) 2.38 (1.15
      4.90)]. CONCLUSIONS: A combined staging system that incorporates distribution of
      lymph nodes relative to the diaphragm refines prognostication after esophagectomy
      as assessed in the resected specimen and pretreatment as assessed by EUS. This
      improved staging has the potential to have a great impact on clinical decision
      making as to whether to embark upon potentially curative or palliative
      treatments.

PMID- 24101017
TI  - Management of early-stage esophageal neoplasia (MESEN) consensus.
AB  - BACKGROUND: Treatment of esophageal adenocarcinoma often involves surgical
      resection. Newer technologies in interventional endoscopy have led to a
      substantial paradigm shift in the management of early-stage neoplasia in
      Barrett's esophagus comprising high-grade dysplasia (HGD), intramucosal
      carcinoma, and, in some cases, submucosal carcinoma. However, there has been no
      consensus regarding the indications for esophageal preservation in these cases.
      In this work, consensus guidelines were established for the management of early
      stage esophageal neoplasia considering clinically relevant aspects (age,
      comorbidities, and social environment) in each scenario. METHODS: Seventeen
      experts were invited to participate based on their background and clinical
      expertise at high-volume centers. A questionnaire was created that included four
      clinical scenarios covering a wide range of situations within HGD and/or early
      esophageal neoplasia, particularly where controversies are likely to exist. Each
      of the clinical scenarios was open to discussion subdivided by patient age (20,
      50, and 80 s). For each clinical scenario an expert was chosen to defend that
      position. Each defense triggered a subsequent discussion during a consensus
      meeting. Conclusions of that discussion together with an accompanying literature
      analysis allowed experts to confirm or change their original choices and served
      as the basis for the recommendations stated in this article. RESULTS: There was
      100 % consensus supporting esophageal preservation in patients with HGD,
      independent of patient age or Barrett's length. In patients with T1a
      adenocarcinoma, consensus for preservation was not reached (65 %) for young and
      middle-aged individuals but was supported for elderly patients (100 %). For T1b
      adenocarcinoma, consensus was reached for surgical resection (90 %), leaving
      organ preservation for patients with very low risk of nodal invasion or poor
      surgical candidates. CONCLUSION: Advances in endoscopic imaging and therapy allow
      for organ preservation in most settings of early-stage neoplasia of the
      esophagus, provided that the patient understands the implications of this
      decision.

PMID- 24101019
TI  - Oncologic outcomes of thoracoscopic esophagectomy with extended lymph node
      dissection: 10-year experience from a single center.
AB  - BACKGROUND: The oncologic feasibility of video-assisted thoracoscopic (VATS)
      radical esophagectomy for esophageal cancer has yet to be proven. We evaluated
      the oncologic outcome of VATS-esophagectomy by reviewing our 10-year experience,
      with particular emphasis on the effect of lymph node dissection. METHODS: From
      January 2003 to December 2012, 146 patients with esophageal cancer underwent
      completion of VATS-esophagectomy in the left lateral position. RESULTS: The mean
      follow-up period was 37.1 months. Forty-six patients (31.5 %) had recurrence of
      cancer. Primary recurrence was hematogenous, lymphatic, peritoneal dissemination,
      pleural dissemination, locoregional, or port site in 20 (13.7 %), 23 (15.8 %), 2
      (1.4 %), 5 (3.4 %), 4 (2.7 %), and 1 (0.67 %) patients, respectively. Pleural
      dissemination occurred more frequently after noncurative operation than curative
      operation (p = 0.010). The frequency of lymphatic metastasis within the
      mediastinal regional lymph nodes in the dissection field was only 5.5 %. The
      overall 5-year survival rate of stage I, II, and III disease after curative VATS
      esophagectomy was 79.1, 77.9, and 56.7 %, respectively. T4 tumor, lymph node
      metastasis, R1 or 2, and concomitant lymph node metastasis in the cervical,
      mediastinal, and abdominal fields were indicators of unfavorable outcome. The
      lymph nodes in the abdominal region and those around the bilateral recurrent
      laryngeal nerves (RLNs) were frequent metastasis sites. Patients who had
      metastasis only around RLNs had favorable survival comparable to node-negative
      cases after curative VATS-esophagectomy. CONCLUSIONS: Video-assisted thorascopic
      esophagectomy has an excellent locoregional control effect with favorable
      oncologic outcome. The lymph node dissection procedure by VATS-esophagectomy has
      survival benefit for the patients having lymph node metastasis around bilateral
      RLNs.

PMID- 24101020
TI  - Cost-effectiveness of surgery in low- and middle-income countries: a systematic
      review.
AB  - BACKGROUND: There is increasing interest in provision of essential surgical care
      as part of public health policy in low- and middle-income countries (LMIC).
      Relatively simple interventions have been shown to prevent death and disability.
      We reviewed the published literature to examine the cost-effectiveness of simple
      surgical interventions which could be made available at any district hospital,
      and compared these to standard public health interventions. METHODS: PubMed and
      EMBASE were searched using single and combinations of the search terms
      "disability adjusted life year" (DALY), "quality adjusted life year," "cost
      effectiveness," and "surgery." Articles were included if they detailed the cost
      effectiveness of a surgical intervention of relevance to a LMIC, which could be
      made available at any district hospital. Suitable articles with both cost and
      effectiveness data were identified and, where possible, data were extrapolated to
      enable comparison across studies. RESULTS: Twenty-seven articles met our
      inclusion criteria, representing 64 LMIC over 16 years of study. Interventions
      that were found to be cost-effective included cataract surgery (cost/DALY averted
      range US$5.06-$106.00), elective inguinal hernia repair (cost/DALY averted range
      US$12.88-$78.18), male circumcision (cost/DALY averted range US$7.38-$319.29),
      emergency cesarean section (cost/DALY averted range US$18-$3,462.00), and cleft
      lip and palate repair (cost/DALY averted range US$15.44-$96.04). A small district
      hospital with basic surgical services was also found to be highly cost-effective
      (cost/DALY averted 1 US$0.93), as were larger hospitals offering emergency and
      trauma surgery (cost/DALY averted US$32.78-$223.00). This compares favorably with
      other standard public health interventions, such as oral rehydration therapy
      (US$1,062.00), vitamin A supplementation (US$6.00-$12.00), breast feeding
      promotion (US$930.00), and highly active anti-retroviral therapy for HIV
      (US$922.00). CONCLUSIONS: Simple surgical interventions that are life-saving and
      disability-preventing should be considered as part of public health policy in
      LMIC. We recommend an investment in surgical care and its integration with other
      public health measures at the district hospital level, rather than investment in
      single disease strategies.

PMID- 24101021
TI  - State of the art of robotic surgery in organ transplantation.
AB  - Within the last two decades the application of minimally invasive surgical
      technologies has shown significant benefits when it comes to complex surgical
      procedures. Lower rates of complications and higher patient satisfaction are
      commonly reported. Until recently these benefits were inaccessible for patients
      with solid organ transplantation, because conventional laparoscopy was seen as
      nonapplicable in such technically demanding procedures. The introduction of the
      da Vinci Robotic Surgical System, with its inherent advantages, has expanded the
      ability to complete solid organ transplantation in a minimally invasive fashion.
      Robotic applications in kidney, pancreas, and liver transplantation have been
      reported. The initial results showed the viability of this technique in the
      field. The most extensive experience has been described in kidney
      transplantation. Over 700 donor nephrectomies and more than 70 renal transplants
      have been performed successfully with the robotic system. The proven advantage of
      the robotic technique, especially in obese kidney recipients, is a significantly
      lower rate of surgical site infection, which in these highly immunosuppressed
      patients is reflected in superior outcomes. The first results in pancreas
      transplantation and living donor hepatectomy are very promising; however, larger
      series are needed in order to address the value of the robotic surgery in these
      areas of solid organ transplantation.

PMID- 24101022
TI  - Defining anatomical landmarks for robotic facelift thyroidectomy.
AB  - BACKGROUND: Robotic facelift thyroidectomy (RFT) is a straightforward remote
      access thyroidectomy technique. While the anatomy encountered during RFT is well
      known to surgeons, the vector of approach during this technique may be less
      familiar. In order to facilitate safe and efficient performance of RFT, the
      relationships of key anatomical landmarks associated with this technique were
      determined. METHODS: Eight anatomical dissections were performed in cadavers and
      included performance of RFT and definition of discrete anatomical relationships.
      Morphologic assessments of the great auricular nerve (GAN), omohyoid (OH) muscle,
      inferior constrictor (IC) muscle, and recurrent laryngeal nerve (RLN) were
      conducted. RESULTS: The mean distance from the incision apex to the anterior and
      posterior aspects of the GAN were 3.8 +/- 1.2 and 7.7 +/- 0.8 cm. From the apex
      of the incision to the OH muscle was 11.1 +/- 1.7 cm on average. The OH muscle
      was located 1.3 +/- 0.5 cm inferior to an axial line drawn through the inferior
      aspect of the thyroid notch. The anterior branch of the RLN was identified
      coursing deep to the inferior margin of the IC muscle a mean of 1.2 +/- 0.2 cm
      lateral to the origin of this muscle on the cricoid cartilage. CONCLUSIONS:
      Characterization of the key anatomical landmarks of the lateral neck and thyroid
      compartment associated with RFT, including the GAN, OH muscle, and RLN, allows
      for rapid recognition of these critical structures during this operation.
      Surgeons learning this approach should be familiar with these relationships.

PMID- 24101023
TI  - Clinical utility of a novel hybrid position combining the left lateral decubitus
      and prone positions during thoracoscopic esophagectomy.
AB  - BACKGROUND: We developed a hybrid of the prone and left lateral decubitus
      positions for thoracoscopic esophagectomy (TE) in 2009. This study aimed to
      evaluate the feasibility of applying this novel TE position. METHODS: We
      retrospectively analyzed 78 patients who underwent TE at our institution between
      2005 and 2010. Altogether, 33 patients underwent TE in the left lateral decubitus
      position (LD-TE) from 2005 to 2008, and 45 underwent TE in the hybrid position
      (hybrid-TE) from 2009 to 2010. Radical lymphadenectomy along the bilateral
      recurrent laryngeal nerves was performed in both groups. The thoracic duct was
      preserved in the LD-TE group and resected in the hybrid-TE group. In the LD-TE
      group, all thoracic procedures were performed with the patient in the left
      lateral decubitus position. In the hybrid-TE group, the upper mediastinal
      procedure was performed with the patient in the left lateral decubitus position,
      and procedures at the middle and lower mediastinum were performed with the
      patient in the prone position under CO2 pneumothorax. RESULTS: Hybrid-TE was
      associated with increased operating time. The number of harvested mediastinal
      nodes and the PaO2/FiO2 ratio on postoperative day 1 were both greater in this
      position. Although vocal cord palsy was observed more frequently in the hybrid-TE
      group, there was no significant difference in the rate of other complications or
      in-hospital mortality between the two groups. CONCLUSIONS: The novel hybrid
      position is believed feasible for use during TE. We believe that this position
      facilitates a more radical mediastinal lymphadenectomy with minimal
      intraoperative pulmonary damage.

PMID- 24101024
TI  - Transanal endoscopic microsurgery (TEM) facilitated by video-assistance and anal
      insertion of a single-incision laparoscopic surgery (SILS((r)))-port: preliminary
      experience.
AB  - OBJECTIVE: Transanal endoscopic microsurgery (TEM) is an established method for
      the resection of benign and early malignant rectal lesions. Very recently, TEM
      via an anally inserted single incision laparoscopic surgery (SILS((r)))-port has
      been proposed to overcome remaining obstacles of the classical TEM equipment.
      METHODS: Nine patients with a total of 12 benign or early stage malignant rectal
      polyps were operated using the SILS((r))-port for TEM. Patients' and polyps'
      characteristics, perioperative and postoperative complications, as well as
      operating and hospitalization time were recorded. RESULTS: All 12 polyps (ten low
      grade adenoma, one high-grade adenoma, one pT2 carcinoma [preoperatively staged
      as T1]) were resected. Local full-thickness bowel wall resection was performed
      for three lesions and submucosal resection for nine lesions. Median operating
      time was 64 (range 30-180) min. No conversion to laparoscopic or open techniques
      was necessary. The median maximum diameter of the specimen was 25 (range 3-60)
      mm, fragmentation of polyps was avoidable in 11 of 12 (92 %) lesions, and
      resection margins were histologically clear in 11 of 12 (92 %) polyps. Only one
      patient, in whom three lesions were resected, experienced a complication as
      postoperative hemorrhage. No mortality occurred. Median hospitalization time was
      four (range 1-14) days. CONCLUSIONS: SILS((r))-TEM is a feasible and safe method,
      providing numerous advantages in application, handling, and economy compared with
      the classical TEM technique. SILS((r))-TEM might become a promising alternative
      to classical TEM. Randomized, controlled trials comparing safety and efficacy of
      both instrumental settings will be needed in the future.

PMID- 24101025
TI  - "Cherry picking", a multiple non-anatomic liver resection technique, as a
      promising option for diffuse liver metastases in patients with neuroendocrine
      tumours.
AB  - INTRODUCTION: Liver metastases of GEP-NETs are a known major prognostic factor
      with a strong effect on patients' survival. To date, various treatment options
      are available, whereas surgery remains the only curative option. Because large
      liver resections often cannot be performed due to insufficient remnant liver
      volume, a special operative technique, "cherry picking" (multiple nonanatomic
      liver resections), can be used as a tissue-preserving procedure. METHODS: Of 91
      patients with various GEP-NETs, 16 patients were identified with synchronous or
      metachronous multifocal, bilobular liver metastases (>10). All were treated with
      "cherry picking." Patient records were reviewed retrospectively and clinical data
      and pathology results were analyzed. RESULTS: Mean survival after primary tumour
      resection was 82.8 versus 41.2 months after liver surgery. All 16 patients are
      still alive. Mean recurrence-free survival after primary tumour operation was
      49.8 versus 24.6 months after liver surgery. Complications of cherry picking
      included two postoperative biliary leakages and three small hepatic abscesses
      (conservative/interventional approach 25 % (n = 4), surgical approach 6.25 % (n =
      1). There was no postoperative mortality. Initial hormonal symptoms (5/16
      patients) completely disappeared postoperatively in 2 patients and were
      significantly decreased in 3 patients. CONCLUSIONS: The tissue-preserving
      surgical technique "cherry picking" has developed due to improved imaging
      techniques and increased knowledge in liver anatomy, which has helped to make
      this approach safer and easier. Highly selected patients with multiple bilobular
      liver metastases of GEP-NET can benefit from this special surgical approach, also
      applicable for recurrent metastases.

PMID- 24101026
TI  - Muscle function is impaired in patients with "asymptomatic" primary
      hyperparathyroidism.
AB  - BACKGROUND: Patients with "asymptomatic" primary hyperparathyroidism (PHPT) often
      describe improvement after surgery. METHODS: We evaluated muscle and balance
      function, quality of life (QoL), and well-being in 58 PHPT patients and 58
      population-based matched controls in a cross-sectional study. We tested whether
      patients considered "asymptomatic" according to international guidelines have
      functional impairment. RESULTS: Mean age of the patients and controls was 59
      years, and 47 (81 %) were women. Patients had higher levels of plasma PTH and
      ionized calcium. Creatinine and 25-hydroxyvitamin D levels did not differ between
      groups. Altogether, 16 (28 %) patients were "asymptomatic." Compared with
      controls, PHPT was associated with significantly lower QoL in all eight domains
      of the short form-36 questionnaire, lower well-being (WHO Five Well-Being Index;
      p < 0.001), and impaired postural stability during normal standing with eyes open
      (p < 0.05) or closed (p < 0.001). Maximum isometric muscle strength was reduced
      in both upper (p < 0.01) and lower (p < 0.001) extremities. Physical performance
      was decreased during 10 repeated chair stands (p < 0.001) and time to walk 3 m
      forward and back (p < 0.05). Restricting analyses to "asymptomatic" patients
      showed significantly lower muscle strength at knee extension and flexion and
      impaired postural stability than in matched controls. CONCLUSIONS: PHPT is
      associated with deleterious effects on muscles and QoL. Impairments also apply to
      patients with mild disease, normally considered "asymptomatic." This may explain
      why "asymptomatic" patients report improvements following surgery. The impaired
      muscle function may contribute to increased fracture risk independent of bone
      mineral density.

PMID- 24101027
TI  - An alternative therapy for HCC with portal vein tumor thrombosis: Y-90
      radioembolization.

PMID- 24101028
TI  - Prognostic value of mitochondrial DNA content and G10398A polymorphism in non
      small cell lung cancer.
AB  - Non-small cell lung cancer (NSCLC) is one of the leading causes of cancer-related
      mortality worldwide. Mitochondrial dysfunction has been postulated to render
      cancer cells resistant to apoptosis based on the Warburg hypothesis. However, few
      studies have investigated the prognostic value of mitochondrial DNA (mtDNA)
      content and G10398A polymorphism in NSCLC patients. mtDNA copy number and G10398A
      polymorphism in 128 NSCLC tissue samples were assessed by real-time PCR (RT-PCR)
      and PCR-RFLP respectively, and their relationship to prognosis were analyzed by
      survival analysis and Cox proportional hazards model. In vitro, an mtDNA deletion
      A549 rho(0) cell model was utilized to assess the function of mtDNA on
      radiosensitivity. Cell cycle distribution and reactive oxygen species (ROS) were
      analyzed to elucidate the potential mechanisms. For the whole group, the median
      follow-up time and overall survival time were 22.5 and 23.4 months, respectively.
      Patients with high mtDNA content had a marginally longer survival time than
      patients with low mtDNA content (P=0.053). Moreover, patients with high mtDNA
      content plus 10398G had a significantly longer overall survival time compared
      with those having low mtDNA content plus 10398A (47 vs. 27 months, P<0.05). In
      addition, multivariate analysis showed that stage and low mtDNA content plus
      10398A were the two most independent prognostic factors. In vitro, the A549
      rho(0) cells showed more resistance to radiation than rho(+) cells. Following
      radiation, rho(0) cells showed delayed G2 arrest and lower ROS level as compared
      to rho(+) cells. In conclusion, the present study suggests that in patients with
      NSCLC, low mtDNA content plus 10398A could be a marker of poor prognosis which is
      associated with resistance to anticancer treatment caused by low mtDNA content
      plus 10398A polymorphism resulting in mitochondrial dysfunction.

PMID- 24101029
TI  - Combined management of atrial fibrillation and heart failure: case studies.
AB  - Atrial fibrillation (AF) and heart failure (HF) are omnipresent cardiovascular
      disorders with a substantial impact on morbidity and mortality. As both share
      common risk factors, their pathophysiology is highly interrelated and a lot of
      patients present with both conditions. Surprisingly, despite their high
      prevalence, there is a paucity of evidence regarding the optimal combined
      management of AF and HF. The initial treatment for new-onset AF in the context of
      HF should focus on anticoagulation, rate control and prompt electrical
      cardioversion in case of hemodynamic instability. Subsequently, attention should
      focus upon the underlying pathophysiological substrate. This often requires
      multidisciplinary collaboration, not only between different subspecialties of
      cardiology, but also among medical and paramedical caregivers, especially when
      underlying HF is present. AF often contributes to worsening HF symptoms, but
      options to maintain sinus rhythm are less successful in patients with structural
      heart disease. Therefore, rhythm control strategies, whether medical or through
      catheter/surgical ablation, should target specific groups of patients with a high
      likelihood of perceived benefit. Indeed, morbidity and mortality are similar with
      rate versus rhythm control in the general population. Carefully performed cardiac
      imaging is vital to select these cases that might benefit most from rhythm
      control. A special group of HF patients are the one with cardiac devices, as they
      can be continuously monitored, even through remote care systems. The latter
      likely involves dedicated nurse practitioners and general physicians. Again, a
      collaborative environment with a disease management strategy is needed to ensure
      an optimally working device and maximized benefits for the patient. 

PMID- 24101030
TI  - The mixture of "ecstasy" and its metabolites is toxic to human SH-SY5Y
      differentiated cells at in vivo relevant concentrations.
AB  - The neurotoxicity of "ecstasy" (3,4-methylenedioxymethamphetamine, MDMA) is
      thought to involve hepatic metabolism, though its real contribution is not
      completely understood. Most in vitro neurotoxicity studies concern isolated
      exposures of MDMA or its metabolites, at high concentrations, not considering
      their mixture, as expected in vivo. Therefore, our postulate is that combined
      deleterious effects of MDMA and its metabolites, at low micromolar concentrations
      that may be attained into the brain, may elicit neurotoxicity. Using human SH
      SY5Y differentiated cells as dopaminergic neuronal model, we studied the
      neurotoxicity of MDMA and its MDMA metabolites alpha-methyldopamine and N-methyl
      alpha-methyldopamine and their correspondent glutathione and N-acetylcysteine
      monoconjugates, under isolated exposure and as a mixture, at normothermic or
      hyperthermic conditions. The results showed that the mixture of MDMA and its
      metabolites was toxic to SH-SY5Y differentiated cells, an effect potentiated by
      hyperthermia and prevented by N-acetylcysteine. As a mixture, MDMA and its
      metabolites presented a different toxicity profile, compared to each compound
      alone, even at equimolar concentrations. Caspase 3 activation, increased reactive
      oxygen species production, and intracellular Ca(2+) raises were implicated in the
      toxic effect. The mixture increased intracellular glutathione levels by
      increasing its de novo synthesis. In conclusion, this study demonstrated, for the
      first time, that the mixture of MDMA and its metabolites, at low micromolar
      concentrations, which represents a more realistic approach of the in vivo
      scenario, elicited toxicity to human SH-SY5Y differentiated cells, thus
      constituting a new insight into the context of MDMA-related neurotoxicity. 

PMID- 24101031
TI  - Non-adherence to antibiotic therapy in patients visiting community pharmacies.
AB  - BACKGROUND: Patient non-adherence to antibiotic therapy may lead to therapeutic
      failure, re-infection, and bacterial resistance. Assessing the factors associated
      with this problem is important for promoting rational use of antibiotics.
      OBJECTIVE: This study aimed to measure prevalence and reasons for non-adherence
      to antibiotic treatment and to identify associated factors. METHOD: Patients were
      recruited for the study in community pharmacies in Lisbon, Portugal, from
      February to April, 2009. Data from prescriptions for oral antibiotics were
      collected for adult subjects. Adherence to treatment was assessed with a modified
      Portuguese version of the Morisky scale. Factors associated with non-adherence
      were identified through bivariate analysis and logistic regression models.
      RESULTS: A total of 243 patients were included in the study. They had a mean age
      46.5 +/- 16.6 years and 74.5 % of the sample was female. The prevalence of non
      adherence was 57.7 % and was related to delays and failures in taking the
      prescribed medicine. Increasing age (OR 0.97), difficulty in buying the
      antibiotic (OR 2.34), duration of treatment (OR 1.28), difficulty with ingestion
      (OR 3.08), and satisfaction with the information given by physician (OR 0.33)
      were identified as independent factors associated with non-adherence. CONCLUSION:
      Non-adherence to antibiotics is common in the community setting. Factors related
      to the antibiotic, the patient, and the patient-physician relationship should be
      addressed to promote adherence. Pharmacists should provide information to
      patients about correct use of antibiotics and address barriers to adherence.

PMID- 24101033
TI  - Exalted photocatalytic activity of tetragonal BiVO4 by Er3+ doping through a
      luminescence cooperative mechanism.
AB  - Er-doped BiVO4 are synthesized by means of a surfactant free microwave assisted
      hydrothermal method having good photoactivities under sun-like excitation for the
      degradation of methylene blue. From the structural and morphological
      characterization, it has been stated that the presence of Er(3+) induces a slight
      stabilization of the tetragonal phase, probably due to its incorporation in the
      BiVO4 lattice. The best photocatalytic performances were attained for the samples
      with Er(3+) content higher than 3 at%. The occurrence of the Er(3+) doped
      tetragonal BiVO4 clearly induces higher photocatalytic activities. The existence
      of a luminescence process has been related with the enhanced photoactivity
      observed. 

PMID- 24101032
TI  - Epidemiology of chemotherapy-induced neutropenia at a tertiary university
      hospital in Oman.
AB  - BACKGROUND: Little is known about the incidence and burden of chemotherapy
      induced neutropenia (CIN) in Oman or the Arabian Gulf. OBJECTIVES: To determine
      the epidemiology of CIN at Sultan Qaboos University Hospital in Oman. METHODS: A
      retrospective observational study of all eligible CIN episodes in adult (>18
      years) patients with solid tumors and hematological malignancies at Sultan Qaboos
      University Hospital (SQUH) from January to December 2010. Analyses were performed
      using univariate statistics. RESULTS: A total of 1,357 episodes in 159 patients
      with a mean age of 50 +/- 15 years (19-91) were evaluated. Fifty-four percent (n
      = 86) of the patients were female. A total of 46 % (73/159) of the patients
      developed CIN accounting for 15 % (210/1,357) of all episodes. Twelve percent
      (25/210) of these CIN episodes were associated with fever in 26 % (19/73)
      patients. There was significant association between CIN and chemotherapy regimen
      (P < 0.001), younger age (P < 0.001), low hemoglobin (Hb) levels (P < 0.001) and
      advanced cancer stage (P = 0.006). CONCLUSIONS: This study suggests a high
      incidence of CIN in SQUH patients which resulted in chemotherapy delays, longer
      hospital stays, and inpatient mortality. CIN was significantly correlated with
      chemotherapy regimen, younger age, low Hb levels and cancer stage.

PMID- 24101034
TI  - A novel approach for measuring the intrinsic nanoscale thickness of polymer
      brushes by means of atomic force microscopy: application of a compressible fluid
      model.
AB  - The thickness of a poly(sulfo propyl methacrylate) (PSPM) brush is determined by
      Atomic Force Microscopy (AFM) imaging as a function of the loading force at
      different ionic strengths, ranging from Milli-Q water to 1 M NaCl. Imaging is
      performed both with a sharp tip and a colloidal probe. The brush thickness
      strongly depends both on the applied load and on the ionic strength. A brush
      thickness of 150 nm is measured in Millipore water when applying the minimal
      loading force. Imaging with an 8 MUm silica particle as a colloidal probe results
      in a thickness of 30 nm larger than that measured with the tip. Increasing the
      ionic strength causes the well known reduction of the thickness of the brush. The
      apparent thickness of the brush decreases with increasing loading forces. An
      empirical model analogous to that of a compressible fluid is applied to describe
      the dependence of the apparent thickness of the brush with loading force. The
      model comprises three ionic strength dependent parameters for the brush:
      thickness at infinite compression, energy, and cohesive force. The meaning and
      significance of these parameters are discussed. A particular advantage of the
      model is that it allows for determination of the brush thickness at zero loading
      force. 

PMID- 24101036
TI  - [Efficacy of an internet-delivered aftercare program for patients with chronic
      back pain].
AB  - Chronic back pain leads to high societal costs and severely decreased quality of
      life for the sufferers. Pain treatment aims at sustainable behaviour changes in
      order to positively affect pain development in the medium term. A multicenter,
      randomised control trial was conducted. Participants (N=334) were recruited at 6
      German hospitals and randomly assigned to an Internet-based aftercare
      intervention or treatment-as-usual. Primary endpoint was 12 months after
      treatment termination, primary outcome was pain intensity, and secondary outcomes
      were physical functioning, quality of life, and ability to work.The intervention
      was well accepted by the participants. Its efficacy could not be demonstrated.
      Neither pain intensity nor the secondary outcomes differed between the 2 study
      groups.Possible reasons for disappointing efficacy and preconditions for Internet
      based programs will be discussed. 

PMID- 24101037
TI  - [Patients' experiences and picture processes during the art therapy in a
      psychosomatic day hospital].
AB  - The aim of this study was the examination of the experiences of patients
      participating in an art therapy during a psychosomatic day hospital. The data
      basis were 15 transliterated interviews from the end of the treatment, conducted
      with a presentation of the pictures painted in the art therapy sessions, as well
      as the digitised pictures. The evaluation was done with a qualitative analysis of
      the interviews and an analysis of the pictures, using a specially-developed
      category system. In the art therapy, most part of the pa-tients dealt with own
      conflicts. Nearly all pa-tients benefitted from the art therapy and indicated an
      improvement of their feeling. The picture processes are different; at the
      beginning, wishes and familiar techniques dominated. Pictures of turning points
      differed in their dimensions. The art therapy was seen as a part of the complete
      treatment in which several therapies assembled. The final interviews were
      experienced as helpful for further reflections. 

PMID- 24101035
TI  - Joint and bone assessment in hand osteoarthritis.
AB  - Hand osteoarthritis (OA) is a common disease frequently affecting middle-aged
      women. Prevalence estimates for OA vary widely depending on the age and sex of
      the population studied, the assessment tools used, and the specific joint sites
      analyzed OA is characterized by the degradation of articular cartilage,
      subchondral bone changes and osteophyte formation at the joint margins leading to
      joint failure. The pathogenesis of the disease and its evolution are
      multifactorial involving biomechanical, metabolic, hormonal, and genetic factors.
      Moreover, the role of inflammation has recently been advanced as pivotal in OA
      onset and progression. In particular, an uncommon variant of hand OA, erosive
      hand OA, is characterized by inflammatory and degenerative interphalangeal
      proximal and distal joints. The diagnosis of different types of hand OA is
      centered on clinical and laboratory investigations which can distinguish the
      peculiar aspects of these forms. Joint and bone assessments in hand OA are widely
      studied but there is no agreement with regard to established parameters to make a
      definitive diagnosis. This report focuses on the laboratory and clinimetric
      assessments that can be used to distinguish hand OA subtypes and addresses the
      debatable association with low bone mineral density in osteoporosis. 

PMID- 24101038
TI  - Rituximab, methotrexate, procarbazine, and vincristine followed by consolidation
      reduced-dose whole-brain radiotherapy and cytarabine in newly diagnosed primary
      CNS lymphoma: final results and long-term outcome.
AB  - PURPOSE: A multicenter phase II study was conducted to assess the efficacy of
      rituximab, methotrexate, procarbazine, and vincristine (R-MPV) followed by
      consolidation reduced-dose whole-brain radiotherapy (rdWBRT) and cytarabine in
      primary CNS lymphoma. PATIENTS AND METHODS: Patients received induction
      chemotherapy with R-MPV (five to seven cycles); those achieving a complete
      response (CR) received rdWBRT (23.4 Gy), and otherwise, standard WBRT was offered
      (45 Gy). Consolidation cytarabine was given after the radiotherapy. The primary
      end point was 2-year progression-free survival (PFS) in patients receiving
      rdWBRT. Exploratory end points included prospective neuropsychological
      evaluation, analysis of magnetic resonance imaging (MRI) white matter changes
      using the Fazekas scale, and evaluation of the apparent diffusion coefficient
      (ADC) as a prognostic factor. RESULTS: Fifty-two patients were enrolled, with
      median age of 60 years (range, 30 to 79 years) and median Karnofsky performance
      score of 70 (range, 50 to 100). Thirty-one patients (60%) achieved a CR after R
      MPV and received rdWBRT. The 2-year PFS for this group was 77%; median PFS was
      7.7 years. Median overall survival (OS) was not reached (median follow-up for
      survivors, 5.9 years); 3-year OS was 87%. The overall (N = 52) median PFS was 3.3
      years, and median OS was 6.6 years. Cognitive assessment showed improvement in
      executive function (P < .01) and verbal memory (P < .05) after chemotherapy, and
      follow-up scores remained relatively stable across the various domains (n = 12).
      All examined MRIs (n = 28) displayed a Fazekas score of <= 3, and no patient
      developed scores of 4 to 5; differences in ADC values did not predict response (P
      = .15), PFS (P = .27), or OS (P = .33). CONCLUSION: R-MPV combined with
      consolidation rdWBRT and cytarabine is associated with high response rates, long
      term disease control, and minimal neurotoxicity.

PMID- 24101039
TI  - Design considerations for dose-expansion cohorts in phase I trials.
AB  - Phase I trials are increasingly including dose-expansion cohorts after the
      maximum-tolerated dose (MTD) has been reached to better characterize the toxicity
      profile or identify early signs of efficacy within a specific disease population.
      This article provides guidelines on how to monitor safety and re-evaluate the MTD
      using data obtained from expansion cohorts of phase I protocols. We illustrate
      how to implement a sequential monitoring rule for safety using a completed phase
      I trial that included an expansion cohort. We compare the accuracy of the revised
      MTD with the MTD obtained before expansion and with the true MTD based on
      simulated trials. The percent of trials that led to a change in the MTD, how far
      the revised MTD was from the true MTD, and the toxicity rates associated with
      each level are reported. When toxicity outcomes from the expansion cohort are
      taken into account, there is a 50% chance that a new, higher MTD will be
      recommended. Significant improvement in the accuracy of the MTD is obtained 30%
      of the time (ie, revised MTD is exactly the true MTD), and moderate improvement
      is obtained 80% of the time when the revised MTD is within a level from true MTD.
      Failure to include toxicity outcomes from additional patients treated during the
      expansion phase may result in a less accurate estimate of the MTD. This article
      provides investigators of phase I protocols with methodological tools to monitor
      safety and/or efficacy for patients accrued during the expansion phase and to
      update or confirm the established MTD. 

PMID- 24101040
TI  - Dose-dense temozolomide for newly diagnosed glioblastoma: a randomized phase III
      clinical trial.
AB  - PURPOSE: Radiotherapy with concomitant and adjuvant temozolomide is the standard
      of care for newly diagnosed glioblastoma (GBM). O(6)-methylguanine-DNA
      methyltransferase (MGMT) methylation status may be an important determinant of
      treatment response. Dose-dense (DD) temozolomide results in prolonged depletion
      of MGMT in blood mononuclear cells and possibly in tumor. This trial tested
      whether DD temozolomide improves overall survival (OS) or progression-free
      survival (PFS) in patients with newly diagnosed GBM. PATIENTS AND METHODS: This
      phase III trial enrolled patients older than age 18 years with a Karnofsky
      performance score of >= 60 with adequate tissue. Stratification included clinical
      factors and tumor MGMT methylation status. Patients were randomly assigned to
      standard temozolomide (arm 1) or DD temozolomide (arm 2) for 6 to 12 cycles. The
      primary end point was OS. Secondary analyses evaluated the impact of MGMT status.
      RESULTS: A total of 833 patients were randomly assigned to either arm 1 or arm 2
      (1,173 registered). No statistically significant difference was observed between
      arms for median OS (16.6 v 14.9 months, respectively; hazard ratio [HR], 1.03; P
      = .63) or median PFS (5.5 v 6.7 months; HR, 0.87; P = .06). Efficacy did not
      differ by methylation status. MGMT methylation was associated with improved OS
      (21.2 v 14 months; HR, 1.74; P < .001), PFS (8.7 v 5.7 months; HR, 1.63; P <
      .001), and response (P = .012). There was increased grade >= 3 toxicity in arm 2
      (34% v 53%; P < .001), mostly lymphopenia and fatigue. CONCLUSION: This study did
      not demonstrate improved efficacy for DD temozolomide for newly diagnosed GBM,
      regardless of methylation status. However, it did confirm the prognostic
      significance of MGMT methylation. Feasibility of large-scale accrual, prospective
      tumor collection, and molecular stratification was demonstrated.

PMID- 24101041
TI  - Psychosocial problems of teenagers who have a parent with cancer: a population
      based case-control study (young-HUNT study).
AB  - PURPOSE: High prevalence of psychosocial problems has been observed in clinical
      studies of teenagers who have a parent with cancer. In contrast, we used a
      population-based design to study such problems in teenagers who have a parent
      with cancer (cases) compared with matched teenagers with cancer-free parents
      (controls). We hypothesized that higher prevalence of psychosocial problems would
      be observed in cases compared with controls and that sex differences would be
      observed between cases and controls. METHODS: We used data from a cross-sectional
      population-based survey of teenagers (Young-HUNT study). Among 8,986 teenage
      participants, 120 of their parents had invasive cancer before the Young-HUNT
      study according to the Norwegian Cancer Registry. These parents had 143 teenagers
      (cases) participating in the Young-HUNT study. Matched on sex, age, and
      municipality, 429 control teenagers with cancer-free parents were drawn from the
      Young-HUNT study. Six psychosocial problems were studied. RESULTS: No significant
      differences in psychosocial problems were observed between cases and controls in
      the total sample. Fewer case daughters reported eating problems compared with
      control daughters, and more case sons reported eating problems compared with
      control sons. More case daughters than case sons reported somatic stress symptoms
      and low self-esteem and displayed more caseness of anxiety/depression. These
      three sex differences were also observed among controls, indicating that they
      were general sex differences. CONCLUSION: In this population-based study,
      teenagers who had a parent with cancer did not have higher prevalence of
      psychosocial problems than controls. Sex differences observed in previous
      clinically based studies were confirmed but may simply reflect sex differences
      observed among teenagers in general.

PMID- 24101042
TI  - Randomized trial of hypofractionated external-beam radiotherapy for prostate
      cancer.
AB  - PURPOSE: To determine if escalated radiation dose using hypofractionation
      significantly reduces biochemical and/or clinical disease failure (BCDF) in men
      treated primarily for prostate cancer. PATIENTS AND METHODS: Between June 2002
      and May 2006, men with favorable- to high-risk prostate cancer were randomly
      allocated to receive 76 Gy in 38 fractions at 2.0 Gy per fraction (conventional
      fractionation intensity-modulated radiation therapy [CIMRT]) versus 70.2 Gy in 26
      fractions at 2.7 Gy per fraction (hypofractionated IMRT [HIMRT]); the latter was
      estimated to be equivalent to 84.4 Gy in 2.0 Gy fractions. High-risk patients
      received long-term androgen deprivation therapy (ADT), and some intermediate-risk
      patients received short-term ADT. The primary end point was the cumulative
      incidence of BCDF. Secondarily, toxicity was assessed. RESULTS: There were 303
      assessable patients with a median follow-up of 68.4 months. No significant
      differences were seen between the treatment arms in terms of the distribution of
      patients by clinicopathologic or treatment-related (ADT use and length) factors.
      The 5-year rates of BCDF were 21.4% (95% CI, 14.8% to 28.7%) for CIMRT and 23.3%
      (95% CI, 16.4% to 31.0%) for HIMRT (P = .745). There were no statistically
      significant differences in late toxicity between the arms; however, in subgroup
      analysis, patients with compromised urinary function before enrollment had
      significantly worse urinary function after HIMRT. CONCLUSION: The
      hypofractionation regimen did not result in a significant reduction in BCDF;
      however, it is delivered in 2.5 fewer weeks. Men with compromised urinary
      function before treatment may not be ideal candidates for this approach.

PMID- 24101043
TI  - Prostate-specific antigen changes as surrogate for overall survival in men with
      metastatic castration-resistant prostate cancer treated with second-line
      chemotherapy.
AB  - PURPOSE: Prostate-specific antigen (PSA) kinetics, and more specifically a >= 30%
      decline in PSA within 3 months after initiation of first-line chemotherapy with
      docetaxel, are associated with improvement in overall survival (OS) in men with
      metastatic castration-resistant prostate cancer (mCRPC). The objective of this
      analysis was to evaluate post-treatment PSA kinetics as surrogates for OS in
      patients receiving second-line chemotherapy. PATIENTS AND METHODS: Data from a
      phase III trial of patients with mCRPC randomly assigned to cabazitaxel plus
      prednisone (C + P) or mitoxantrone plus prednisone were used. PSA decline (>= 30%
      and >= 50%), velocity, and rise within the first 3 months of treatment were
      evaluated as surrogates for OS. The Prentice criteria, proportion of treatment
      explained (PTE), and meta-analytic approaches were used as measures of surrogacy.
      RESULTS: The observed hazard ratio (HR) for death for patients treated with C + P
      was 0.66 (95% CI, 0.55 to 0.79; P < .001). Furthermore, a >= 30% decline in PSA
      was a statistically significant predictor of OS (HR for death, 0.52; 95% CI, 0.43
      to 0.64; P < .001). Adjusting for treatment effect, the HR for a >= 30% PSA
      decline was 0.50 (95% CI, 0.40 to 0.62; P < .001), but treatment remained
      statistically significant, thus failing the third Prentice criterion. The PTE for
      a >= 30% decline in PSA was 0.34 (95% CI, 0.11 to 0.56), indicating a lack of
      surrogacy for OS. The values of R(2) were < 1, suggesting that PSA decline was
      not surrogate for OS. CONCLUSION: Surrogacy for any PSA-based end point could not
      be demonstrated in this analysis. Thus, the benefits of cabazitaxel in mediating
      a survival benefit are not fully captured by early PSA changes.

PMID- 24101044
TI  - The art of not being a difficult parent.

PMID- 24101045
TI  - Recommendations for human epidermal growth factor receptor 2 testing in breast
      cancer: American Society of Clinical Oncology/College of American Pathologists
      clinical practice guideline update.
AB  - PURPOSE: To update the American Society of Clinical Oncology (ASCO)/College of
      American Pathologists (CAP) guideline recommendations for human epidermal growth
      factor receptor 2 (HER2) testing in breast cancer to improve the accuracy of HER2
      testing and its utility as a predictive marker in invasive breast cancer.
      METHODS: ASCO/CAP convened an Update Committee that included coauthors of the
      2007 guideline to conduct a systematic literature review and update
      recommendations for optimal HER2 testing. RESULTS: The Update Committee
      identified criteria and areas requiring clarification to improve the accuracy of
      HER2 testing by immunohistochemistry (IHC) or in situ hybridization (ISH). The
      guideline was reviewed and approved by both organizations. RECOMMENDATIONS: The
      Update Committee recommends that HER2 status (HER2 negative or positive) be
      determined in all patients with invasive (early stage or recurrence) breast
      cancer on the basis of one or more HER2 test results (negative, equivocal, or
      positive). Testing criteria define HER2-positive status when (on observing within
      an area of tumor that amounts to > 10% of contiguous and homogeneous tumor cells)
      there is evidence of protein overexpression (IHC) or gene amplification (HER2
      copy number or HER2/CEP17 ratio by ISH based on counting at least 20 cells within
      the area). If results are equivocal (revised criteria), reflex testing should be
      performed using an alternative assay (IHC or ISH). Repeat testing should be
      considered if results seem discordant with other histopathologic findings.
      Laboratories should demonstrate high concordance with a validated HER2 test on a
      sufficiently large and representative set of specimens. Testing must be performed
      in a laboratory accredited by CAP or another accrediting entity. The Update
      Committee urges providers and health systems to cooperate to ensure the highest
      quality testing. This guideline was developed through a collaboration between the
      American Society of Clinical Oncology and the College of American Pathologists
      and has been published jointly by invitation and consent in both Journal of
      Clinical Oncology and the Archives of Pathology & Laboratory Medicine.

PMID- 24101046
TI  - Signaling control by epidermal growth factor receptor and MET: rationale for
      cotargeting strategies in lung cancer.

PMID- 24101048
TI  - Net clinical benefit analysis of radiation therapy oncology group 0525: a phase
      III trial comparing conventional adjuvant temozolomide with dose-intensive
      temozolomide in patients with newly diagnosed glioblastoma.
AB  - PURPOSE: Radiation Therapy Oncology Group trial 0525 tested whether dose
      intensifying temozolomide versus standard chemoradiotherapy improves overall
      survival (OS) or progression-free survival (PFS) in newly diagnosed glioblastoma.
      Tests of neurocognitive function (NCF) and symptoms (using the MD Anderson
      Symptom Inventory-Brain Tumor module; MDASI-BT) and of quality of life (European
      Organisation for the Research and Treatment of Cancer Quality of Life
      Questionnaire [EORTC QLQ] -C30/BN20) examined the net clinical benefit (NCB) of
      therapy. PATIENTS AND METHODS: NCF tests (Hopkins Verbal Learning Test-Revised,
      Trail Making Test, and Controlled Oral Word Association), MDASI-BT, and EORTC QLQ
      C30/BN20 were completed in a subset of patients. Multivariate Cox proportional
      hazard regression modeling determined the prognostic value of baseline and early
      change from baseline to cycle 1 for OS and PFS. Two-sample proportional test
      statistic was used to evaluate differences between treatments (dose-dense v
      standard-dose) on NCB measures from baseline to cycle 4 in stable patients.
      RESULTS: Overall, 182 patients participated in the study. Baseline NCF tests and
      the physical functioning quality of life scale were associated with OS and PFS.
      Baseline to cycle 1 in all NCB components were associated with OS and PFS. There
      was greater deterioration in the dose-dense arm from baseline to cycle 4 in the
      Global Health and Motor Function subscales (EORTC QLQ-C30/BN20) as well as in
      overall symptom burden, overall symptom interference, and activity-related
      symptom interference subscales (MDASI-BT). There were no between-arm differences
      in NCF. CONCLUSION: Longitudinal collection of NCB measures is feasible in
      cooperative group studies and provides an added dimension to standard outcome
      measures. Greater adverse symptom burden and functional interference, as well as
      decreased global health and motor function were observed in patients randomly
      assigned to the dose-dense arm. Baseline and early change in NCB measures were
      associated with decreased rates of survival.

PMID- 24101047
TI  - Emerging paradigms in the development of resistance to tyrosine kinase inhibitors
      in lung cancer.
AB  - The success of tyrosine kinase inhibitors (TKIs) in select patients with non
      small-cell lung cancer (NSCLC) has transformed management of the disease, placing
      new emphasis on understanding the molecular characteristics of tumor specimens.
      It is now recognized that genetic alterations in the epidermal growth factor
      receptor (EGFR) and anaplastic lymphoma kinase (ALK) define two unique subtypes
      of NSCLC that are highly responsive to genotype-directed TKIs. Despite this
      initial sensitivity, however, the long-term effectiveness of such therapies is
      universally limited by the development of resistance. Identifying the mechanisms
      underlying this resistance is an area of intense, ongoing investigation. In this
      review, we provide an overview of recent experience in the field, focusing on
      results from preclinical resistance models and studies of patient-derived, TKI
      resistant tumor specimens. Although diverse TKI resistance mechanisms have been
      identified within EGFR-mutant and ALK-positive patients, we highlight common
      principles of resistance shared between these groups. These include the
      development of secondary mutations in the kinase target, gene amplification of
      the primary oncogene, and upregulation of bypass signaling tracts. In EGFR-mutant
      and ALK-positive patients alike, acquired resistance may also be a dynamic and
      multifactorial process that may necessitate the use of treatment combinations. We
      believe that insights into the mechanisms of TKI resistance in patients with EGFR
      mutations or ALK rearrangements may inform the development of novel treatment
      strategies in NSCLC, which may also be generalizable to other kinase-driven
      malignancies. 

PMID- 24101049
TI  - Reply to L. Battistuzzi et Al.

PMID- 24101050
TI  - Communication of clinically useful next-generation sequencing results to at-risk
      relatives of deceased research participants: toward active disclosure?

PMID- 24101051
TI  - Preservation of cognitive function in primary CNS lymphoma survivors a median of
      12 years after enhanced chemotherapy delivery.

PMID- 24101052
TI  - Long-term cardiovascular mortality in patients with differentiated thyroid
      carcinoma: an observational study.
AB  - PURPOSE: The primary aim was to study the risk of cardiovascular mortality in
      patients with differentiated thyroid carcinoma (DTC). Secondary aims were to
      evaluate all-cause mortality and explore the relation between thyroid-stimulating
      hormone (TSH; also known as thyrotropin) level and these outcome parameters.
      PATIENTS AND METHODS: Subjects from two cohorts were retrospectively compared by
      Cox regression analyses; 524 patients with DTC and 1,572 sex- and age-matched
      controls from a large population-based study in the same geographic region.
      RESULTS: Mean age plus or minus standard deviation was 49 +/- 14 years. Median
      follow-up was 8.5 years (interquartile range [IQR], 4.1 to 15.9 years) for
      patients with DTC and 10.5 years (IQR, 9.9 to 10.9 years) for controls. One
      hundred patients with DTC (19.1%) died, 22 (4.2%) as a result of cardiovascular
      disease, 39 (7.4%) as a result of DTC, and 39 (7.4%) as a result of other/unknown
      causes. Eighty-five controls (5.4%) died, 24 (1.5%) as a result of cardiovascular
      disease and 61 (3.9%) as a result of other/unknown causes. Patients with DTC had
      an increased risk of cardiovascular and all-cause mortality (hazard ratios [HRs],
      3.35 [95% CI, 1.66 to 6.74] and 4.40 [95% CI, 3.15 to 6.14], respectively,
      adjusted for age, sex, and cardiovascular risk factors). Within the DTC group,
      TSH level was predictive for cardiovascular mortality; the adjusted HR was 3.08
      (95% CI, 1.32 to 7.21) for each 10-fold decrease in geometric mean TSH level.
      CONCLUSION: The risk of cardiovascular and all-cause mortality is increased in
      patients with DTC, independent of age, sex, and cardiovascular risk factors. A
      lower TSH level is associated with increased cardiovascular mortality, supporting
      the current European Thyroid Association and the American Thyroid Association
      guidelines of tempering TSH suppression in patients with low risk of cancer
      recurrence. Furthermore, patients with DTC may benefit from assessment and
      treatment of cardiovascular risk factors.

PMID- 24101053
TI  - Randomized phase II trial of Onartuzumab in combination with erlotinib in
      patients with advanced non-small-cell lung cancer.
AB  - PURPOSE: Increased hepatocyte growth factor/MET signaling is associated with poor
      prognosis and acquired resistance to epidermal growth factor receptor (EGFR) 
      targeted drugs in patients with non-small-cell lung cancer (NSCLC). We
      investigated whether dual inhibition of MET/EGFR results in clinical benefit in
      patients with NSCLC. PATIENTS AND METHODS: Patients with recurrent NSCLC were
      randomly assigned at a ratio of one to one to receive onartuzumab plus erlotinib
      or placebo plus erlotinib; crossover was allowed at progression. Tumor tissue was
      required to assess MET status by immunohistochemistry (IHC). Coprimary end points
      were progression-free survival (PFS) in the intent-to-treat (ITT) and MET
      positive (MET IHC diagnostic positive) populations; additional end points
      included overall survival (OS), objective response rate, and safety. RESULTS:
      There was no improvement in PFS or OS in the ITT population (n = 137; PFS hazard
      ratio [HR], 1.09; P = .69; OS HR, 0.80; P = .34). MET-positive patients (n = 66)
      treated with erlotinib plus onartuzumab showed improvement in both PFS (HR, .53;
      P = .04) and OS (HR, .37; P = .002). Conversely, clinical outcomes were worse in
      MET-negative patients treated with onartuzumab plus erlotinib (n = 62; PFS HR,
      1.82; P = .05; OS HR, 1.78; P = .16). MET-positive control patients had worse
      outcomes versus MET-negative control patients (n = 62; PFS HR, 1.71; P = .06; OS
      HR, 2.61; P = .004). Incidence of peripheral edema was increased in onartuzumab
      treated patients. CONCLUSION: Onartuzumab plus erlotinib was associated with
      improved PFS and OS in the MET-positive population. These results combined with
      the worse outcomes observed in MET-negative patients treated with onartuzumab
      highlight the importance of diagnostic testing in drug development.

PMID- 24101054
TI  - ATLAS: randomized, double-blind, placebo-controlled, phase IIIB trial comparing
      bevacizumab therapy with or without erlotinib, after completion of chemotherapy,
      with bevacizumab for first-line treatment of advanced non-small-cell lung cancer.
AB  - PURPOSE: This phase III trial was performed to assess the potential benefit of
      adding maintenance erlotinib to bevacizumab after a first-line chemotherapy
      regimen with bevacizumab for advanced non-small-cell lung cancer (NSCLC).
      PATIENTS AND METHODS: One thousand one hundred forty-five patients with
      histologically or cytologically confirmed NSCLC (stage IIIB with malignant
      pleural effusion, stage IV, or recurrent) received four cycles of chemotherapy
      plus bevacizumab. Seven hundred forty-three patients without disease progression
      or significant toxicity were then randomly assigned (1:1) to bevacizumab (15
      mg/kg, day 1, 21-day cycle) plus either placebo or erlotinib (150 mg per day).
      The primary end point was progression-free survival (PFS). RESULTS: Median PFS
      from time of random assignment was 3.7 months with bevacizumab/placebo and 4.8
      months with bevacizumab/erlotinib (hazard ratio [HR], 0.71; 95% CI, 0.58 to 0.86;
      P < .001). Median overall survival (OS) times from random assignment were 13.3
      and 14.4 months with bevacizumab/placebo and bevacizumab/erlotinib, respectively
      (HR, 0.92; 95% CI, 0.70 to 1.21; P = .5341). During the postchemotherapy phase,
      there were more adverse events (AEs) overall, more grade 3 and 4 AEs (mainly rash
      and diarrhea), more serious AEs, and more AEs leading to erlotinib/placebo
      discontinuation in the bevacizumab/erlotinib arm versus the bevacizumab/placebo
      arm. The incidence of AEs leading to bevacizumab discontinuation was similar in
      both treatment arms. CONCLUSION: The addition of erlotinib to bevacizumab
      significantly improved PFS but not OS. Although generally well tolerated, the
      modest impact on survival and increased toxicity associated with the addition of
      erlotinib to bevacizumab maintenance mean that this two-drug maintenance regimen
      will not lead to a new postchemotherapy standard of care.

PMID- 24101055
TI  - Prostate cancer and the hypofractionation hypothesis.

PMID- 24101056
TI  - The pursuit of improved physical and mental health.

PMID- 24101057
TI  - Confronting a crisis in cancer care delivery.
AB  - The Institute of Medicine offers a road map for reforming the "chaotic and
      costly" delivery of cancer care in the United States. 

PMID- 24101058
TI  - Substantial health and economic returns from delayed aging may warrant a new
      focus for medical research.
AB  - Recent scientific advances suggest that slowing the aging process (senescence) is
      now a realistic goal. Yet most medical research remains focused on combating
      individual diseases. Using the Future Elderly Model--a microsimulation of the
      future health and spending of older Americans--we compared optimistic "disease
      specific" scenarios with a hypothetical "delayed aging" scenario in terms of the
      scenarios' impact on longevity, disability, and major entitlement program costs.
      Delayed aging could increase life expectancy by an additional 2.2 years, most of
      which would be spent in good health. The economic value of delayed aging is
      estimated to be $7.1 trillion over fifty years. In contrast, addressing heart
      disease and cancer separately would yield diminishing improvements in health and
      longevity by 2060--mainly due to competing risks. Delayed aging would greatly
      increase entitlement outlays, especially for Social Security. However, these
      changes could be offset by increasing the Medicare eligibility age and the normal
      retirement age for Social Security. Overall, greater investment in research to
      delay aging appears to be a highly efficient way to forestall disease, extend
      healthy life, and improve public health.

PMID- 24101059
TI  - More americans living longer with cardiovascular disease will increase costs
      while lowering quality of life.
AB  - In the past several decades, some risk factors for cardiovascular disease have
      improved, while others have worsened. For example, smoking rates have dropped and
      treatment rates for cardiovascular disease have increased-factors that have made
      the disease less fatal. At the same time, Americans' average body mass index and
      incidence of diabetes have increased as the population continues to live longer
      factors that have made cardiovascular disease more prevalent. To assess the
      aggregate impact of these opposing trends, we used the nine National Health and
      Nutrition Examination Survey waves from 1973 to 2010 to forecast total
      cardiovascular disease risk and prevalence from 2015 to 2030. We found that
      continued improvements in cardiovascular disease treatment and declining smoking
      rates will not outweigh the influence of increasing population age and obesity on
      cardiovascular disease risk. Given an aging population, an obesity epidemic, and
      declining mortality from the disease, the United States should expect to see a
      sharp rise in the health care costs, disability, and reductions in quality of
      life associated with increased prevalence of cardiovascular disease. Policies
      that target the treatment of high blood pressure and cholesterol and the
      reduction of obesity will be necessary to curb the imminent spike in
      cardiovascular disease prevalence. 

PMID- 24101060
TI  - Trends underlying employer-sponsored health insurance growth for Americans
      younger than age sixty-five.
AB  - Little is known about the trends in health care spending for the 156 million
      Americans who are younger than age sixty-five and enrolled in employer-sponsored
      health insurance. Using a new source of health insurance claims data, we
      estimated per capita spending, utilization, and prices for this population
      between 2007 and 2011. During this period per capita spending on employer
      sponsored insurance grew at historically slow rates, but still faster than per
      capita national health expenditures. Total per capita spending for employer
      sponsored insurance grew at an average annual rate of 4.9 percent, with
      prescription spending growing at 3.3 percent and medical spending growing at 5.3
      percent. Out-of-pocket medical spending increased at an average annual rate of
      8.0 percent, whereas out-of-pocket prescription drug spending growth was flat.
      Growth in the use of medical services and prescription drugs slowed. Medical
      price growth accelerated, and prescription price growth decelerated. As a result,
      changes in utilization contributed less than changes in price did to overall
      spending growth for those with employer-sponsored insurance.

PMID- 24101061
TI  - Access and cost barriers to mental health care, by insurance status, 1999-2010.
AB  - The cost of mental health services has always been a great barrier to accessing
      care for people with mental health problems. This article documents changes in
      insurance coverage and cost for mental health services for people with public
      insurance, private insurance, and no coverage. In 2009-10 people with mental
      health problems were more likely to have public insurance and less likely to have
      private insurance than in 1999-2000. Although access to specialty care remained
      relatively stable for people with mental illnesses, cost barriers to care
      increased among the uninsured and the privately insured who had serious mental
      illnesses. The rise in cost barriers among those with private insurance suggests
      that the current financing of care in the private insurance market is
      insufficient to alleviate cost burdens and has implications for reforms under the
      Affordable Care Act. People with mental health problems who are newly eligible to
      purchase private insurance under the act might still encounter high cost barriers
      to accessing care. 

PMID- 24101062
TI  - The quality of care delivered to patients within the same hospital varies by
      insurance type.
AB  - In attempting to explain why hospitals vary in the quality of care delivered to
      patients, a considerable body of health policy research points to differences in
      hospital characteristics such as ownership, safety-net status, and geographic
      location as the most important contributing factors. This article examines the
      extent to which a patient's type or lack of insurance may also play a role in
      determining the quality of care received at any given hospital. We compared
      within-hospital quality, as measured by risk-adjusted mortality rates, for
      patients according to their insurance status. We examined the Agency for
      Healthcare Research and Quality's innovative Inpatient Quality Indicators and
      pooled 2006-08 State Inpatient Database records from eleven states. We found that
      privately insured patients had lower risk-adjusted mortality rates than did
      Medicare enrollees for twelve out of fifteen quality measures examined. To a
      lesser extent, privately insured patients also had lower risk-adjusted mortality
      rates than those in other payer groups. Medicare patients appeared particularly
      vulnerable to receiving inferior care. These findings suggest that to help reduce
      care disparities, public payers and hospitals should measure care quality for
      different insurance groups and monitor differences in treatment practices within
      hospitals. 

PMID- 24101064
TI  - Massachusetts General Physicians Organization's quality incentive program
      produces encouraging results.
AB  - Physicians are increasingly becoming salaried employees of hospitals or large
      physician groups. Yet few published reports have evaluated provider-driven
      quality incentive programs for salaried physicians. In 2006 the Massachusetts
      General Physicians Organization began a quality incentive program for its
      salaried physicians. Eligible physicians were given performance targets for three
      quality measures every six months. The incentive payments could be as much as 2
      percent of a physician's annual income. Over thirteen six-month terms, the
      program used 130 different quality measures. Although quality-of-care
      improvements and cost reductions were difficult to calculate, anecdotal evidence
      points to multiple successes. For example, the program helped physicians meet
      many federal health information technology meaningful-use criteria and produced
      $15.5 million in incentive payments. The program also facilitated the adoption of
      an electronic health record, improved hand hygiene compliance, increased
      efficiency in radiology and the cancer center, and decreased emergency department
      use. The program demonstrated that even small incentives tied to carefully
      structured metrics, priority setting, and clear communication can help change
      salaried physicians' behavior in ways that improve the quality and safety of
      health care and ease the physicians' sense of administrative burden.

PMID- 24101063
TI  - Hospitals with higher nurse staffing had lower odds of readmissions penalties
      than hospitals with lower staffing.
AB  - The Affordable Care Act's Hospital Readmissions Reduction Program (HRRP)
      penalizes hospitals based on excess readmission rates among Medicare
      beneficiaries. The aim of the program is to reduce readmissions while aligning
      hospitals' financial incentives with payers' and patients' quality goals. Many
      evidence-based interventions that reduce readmissions, such as discharge
      preparation, care coordination, and patient education, are grounded in the
      fundamentals of basic nursing care. Yet inadequate staffing can hinder nurses'
      efforts to carry out these processes of care. We estimated the effect that nurse
      staffing had on the likelihood that a hospital was penalized under the HRRP.
      Hospitals with higher nurse staffing had 25 percent lower odds of being penalized
      compared to otherwise similar hospitals with lower staffing. Investment in
      nursing is a potential system-level intervention to reduce readmissions that
      policy makers and hospital administrators should consider in the new regulatory
      environment as they examine the quality of care delivered to US hospital
      patients.

PMID- 24101065
TI  - The long wait for medical excellence.
AB  - In October 1997 the book Demanding Medical Excellence: Doctors and Accountability
      in the Information Age provided a pathbreaking examination of the quality of
      American health care. It documented rampant medical error and the absence of
      evidence-based practice, highlighted the potential of electronic health records
      (EHRs), endorsed what is now known as value purchasing, and showed how patients
      could exert more control over their care. Although the book suggested that
      transformational change was imminent, sixteen years later little has changed in
      some areas (medical error), while in others (evidence-based medicine and
      population health) change is only now gaining momentum. The exception is
      technology, where incentives boosted EHR use and the Internet has made a vast
      array of information available to patients. Paradigm shifts are traumatic, and
      only recently has intense financial pressure made greater clinical accountability
      seem less painful than retaining the tradition of untrammeled autonomy. In
      hearing rooms and hospital hallways, the policy conversation is changing. This
      shift, though an unavoidable source of anxiety, nonetheless promises a genuine
      renewal of American medicine.

PMID- 24101066
TI  - Improving the quality of health care: what's taking so long?
AB  - Nearly fourteen years ago the Institute of Medicine's report, To Err Is Human:
      Building a Safer Health System, triggered a national movement to improve patient
      safety. Despite the substantial and concentrated efforts that followed, quality
      and safety problems in health care continue to routinely result in harm to
      patients. Desired progress will not be achieved unless substantial changes are
      made to the way in which quality improvement is conducted. Alongside important
      efforts to eliminate preventable complications of care, there must also be an
      effort to seriously address the widespread overuse of health services. That
      overuse, which places patients at risk of harm and wastes resources at the same
      time, has been almost entirely left out of recent quality improvement endeavors.
      Newer and much more effective strategies and tools are needed to address the
      complex quality challenges confronting health care. Tools such as Lean, Six
      Sigma, and change management are proving highly effective in tackling problems as
      difficult as hand-off communication failures and patient falls. Finally, the
      organizational culture of most American hospitals and other health care
      organizations must change. To create a culture of safety, leaders must eliminate
      intimidating behaviors that suppress the reporting of errors and unsafe
      conditions. Leaders must also hold everyone accountable for adherence to safe
      practices. 

PMID- 24101067
TI  - 'Double jeopardy' measure suggests blacks and hispanics face more severe
      disparities than previously indicated.
AB  - Eliminating disparities in health and health care is a long-standing objective of
      the US government. Racial and ethnic differences in insurance coverage pose a
      major obstacle to achieving this objective. With important coverage provisions of
      the Affordable Care Act beginning to take effect, we propose a new way of
      conceptualizing and quantifying the racial and ethnic disadvantages of
      uninsurance over the course of a lifetime. Using a life expectancy approach, we
      estimate the number of years whites, blacks, and Hispanics can expect to live in
      insurance "double jeopardy": being uninsured while also in lesser health and,
      therefore, at higher risk of needing medical care. Our measures indicate that
      compared to whites, Hispanics and blacks are more likely not only to be uninsured
      at any point throughout most of their lives, but also to spend more years
      uninsured and spend more of these uninsured years at high risk of needing medical
      care. These life expectancy measures--designed for ease of use by policy makers,
      researchers, and the general public--have the potential to reframe the discussion
      of disparities and monitor progress toward their elimination.

PMID- 24101068
TI  - Despite overall improvement in surgical outcomes since 2000, income-related
      disparities persist.
AB  - Despite improvements in health care, disparities in care still exist and are
      widening for some health measures. This study examined postsurgical outcomes for
      patients from low-income areas as compared to outcomes for those from high-income
      areas in the United States from 2000 to 2009. We found that postsurgical outcomes
      improved in general, with significant decreases in nine of twelve mortality and
      patient safety measures and an increase in one measure. Patients from low-income
      areas had worse surgical outcomes than those from high-income areas for nine of
      twelve measures in both 2000 and 2009. The disparities in outcomes between low-
      and high-income groups did not change significantly for nine of the twelve
      measures. For the three measures that did change significantly, in only two of
      the cases was the change favorable for patients from low-income areas. These
      findings have implications for efforts to improve surgical outcomes and health
      policy and indicate the need for research on the cause of continued disparities
      in postsurgical outcomes. 

PMID- 24101069
TI  - Accountable care organization formation is associated with integrated systems but
      not high medical spending.
AB  - Medicare's approximately 250 accountable care organizations (ACOs) care for a
      growing portion of all fee-for-service beneficiaries across the United States. We
      examined where ACOs have formed and what regional factors are predictive of ACO
      formation. Understanding these factors could help policy makers foster growth in
      areas with limited ACO development. We found wide variation in ACO formation,
      with large areas, such as the Northwest, essentially empty of ACOs, and others,
      such as the Northeast and Midwest, dense with the organizations. Key regional
      factors associated with ACO formation include a greater fraction of hospital risk
      sharing (capitation), larger integrated hospital systems, and primary care
      physicians practicing in large groups. Area income, Medicare per capita spending,
      Medicare Advantage enrollment rates, and physician density were not associated
      with ACO formation. Together, these results imply that underlying provider
      integration in a region may help drive the formation of ACOs. 

PMID- 24101070
TI  - When medicare cuts hospital prices, seniors use less inpatient care.
AB  - The Affordable Care Act permanently slows the growth in Medicare hospital prices.
      To better understand the effects of those price cuts, we used data from ten
      states for the period 1995-2009 to examine the market-level relationship between
      Medicare prices and hospital utilization among the elderly. Regression analyses
      indicate that a 10 percent reduction in the Medicare price was associated with a
      4.6 percent reduction in discharges among the elderly. This volume response to
      price cuts appears to be accomplished through hospitals' reduction in their
      numbers of staffed beds. They did not leave beds empty; instead, they reduced
      their scale of operations. Based on our results, we conclude that the Affordable
      Care Act will help reduce inpatient hospital utilization in the future. From a
      federal budgetary standpoint, lower utilization is good news, but the
      implications for patient care and health outcomes are not yet clear.

PMID- 24101071
TI  - Providing more home-delivered meals is one way to keep older adults with low care
      needs out of nursing homes.
AB  - Programs that help older adults live independently in the community can also
      deliver net savings to states on the costs of long-term supports and services. We
      estimate that if all states had increased by 1 percent the number of adults age
      sixty-five or older who received home-delivered meals in 2009 under Title III of
      the Older Americans Act, total annual savings to states' Medicaid programs could
      have exceeded $109 million. The projected savings primarily reflect decreased
      Medicaid spending for an estimated 1,722 older adults with low care needs who
      would no longer require nursing home care--instead, they could remain at home,
      sustained by home-delivered meals. Twenty-six states could have realized net
      savings in 2009 from the expansion of their home-delivered meals programs, while
      twenty-two states would have incurred net costs. Programs such as home-delivered
      meals have the potential to provide substantial savings to some states' Medicaid
      programs.

PMID- 24101072
TI  - Biosimilars and the European experience: implications for the United States.
AB  - Biologics are medicines derived from a biological source. Their high prices and
      rapid uptake have raised hopes that with the gradual expiration of patents on the
      first generations of biologics, the advent of lower-cost follow-on products known
      as biosimilars will help "bend the cost curve." Although biosimilars have been
      available since 2006 within the European Union and are expected to save $15-$44
      billion by 2020, the Food and Drug Administration (FDA) has yet to finalize the
      necessary regulatory processes for their approval in the United States. The
      European experience suggests, however, that once these are in place, the US
      biosimilar market may well emerge as bimodal: Initially, modestly discounted
      biosimilars deemed noninterchangeable with the original products will compete to
      become the initial treatment of choice in new patients. Subsequently, a second
      market may be anticipated for those products able to meet the FDA's higher
      standard for "interchangeability." In that market, discounts may be more
      dramatic.

PMID- 24101073
TI  - High-intensity emergency department visits increased in California, 2002-09.
AB  - Increasing use of the emergency department (ED) is well documented, but little is
      known about the type and severity of ED visits or their distribution across
      safety-net and non-safety-net hospitals. We examined the rates of high-intensity
      ED visits--characterized by their use of advanced imaging, consultations with
      specialists, the evaluation of multiple systems, and highly complex medical
      decision making--by patients with a severe, potentially life-threatening illness
      in California from 2002 through 2009. Total annual ED visits increased by 25
      percent, from 9.0 million to 11.3 million, but high-intensity ED visits nearly
      doubled, increasing 87 percent from 778,000 to 1.5 million per year. The
      percentage of ED visits with high-intensity care increased from 9 percent to 13
      percent (a relative increase of 44 percent). Annual ED admissions increased by 39
      percent overall; most of this increase was attributable to high-intensity ED
      admissions, which increased by 88 percent. Safety-net EDs experienced an increase
      in high-intensity visits of 157 percent, compared to an increase of 61 percent at
      non-safety-net EDs. These findings suggest a trend toward intensification of ED
      care, particularly at safety-net hospitals, whose patients may have limited
      access to care outside the ED.

PMID- 24101074
TI  - In the 'gray zone,' a doctor faces tough decisions on infant resuscitation.
AB  - A neonatologist must decide whether to revive a premature baby on the borderline
      of viability. 

PMID- 24101075
TI  - New York State Health Foundation: integrating mental health and substance abuse
      care.
AB  - Roughly half of all people with severe mental disorders also have substance abuse
      problems. Yet their care is fragmented: They are treated by either the mental
      health system or the substance abuse system. In New York State only 10 percent of
      them receive evidence-based treatment for both conditions. Beginning in 2007 the
      New York State Health Foundation and two state agencies--the Office of Mental
      Health and the Office of Alcoholism and Substance Abuse Services--began
      collaborating on ways to integrate the treatment of people with co-occurring
      disorders. The state agencies removed financial and regulatory barriers to
      integrated treatment. The foundation provided funding to establish the Center for
      Excellence in Integrated Care. The center's goal: provide hands-on assistance in
      implementing best practices to at least half of the state's 1,200 mental health
      and substance abuse treatment clinics. An evaluation found that the percentage of
      clinics using best practices doubled after the regulatory and financial changes
      and the center's intervention. This illustrates the potential that foundations,
      governments, and nonprofits, working collaboratively, have to improve the care of
      a neglected and difficult-to-serve population.

PMID- 24101077
TI  - Medical expenses and bankruptcy.

PMID- 24101078
TI  - Medical care and bankruptcy: the author replies.

PMID- 24101079
TI  - Emergency care in Australia.

PMID- 24101080
TI  - Pharmacists and team-based care.

PMID- 24101081
TI  - Pharmacists on care teams: the authors reply.

PMID- 24101082
TI  - Emergency care: the author replies.

PMID- 24101083
TI  - Racial disparities in hospital selection.

PMID- 24101084
TI  - Placebo-controlled trials.

PMID- 24101085
TI  - Demographic factors in immigrants' health care use.

PMID- 24101086
TI  - Immigrants' health care use: the author replies.

PMID- 24101087
TI  - Changes in intestinal permeability after Roux-en-Y gastric bypass.
AB  - BACKGROUND: Roux-en-Y gastric bypass (RYGB) interferes considerably with the
      anatomy and physiology of the gastrointestinal tract. The study of intestinal
      permeability can provide important information regarding changes in the structure
      and function of the mucosal barrier after the procedure. METHODS: The urinary
      excretion rates of lactulose and mannitol after oral intake of both substances
      were evaluated. We also evaluated the lactulose/mannitol excretion ratio. Tests
      were performed during the preoperative period (T0), at the first postoperative
      month (T1), and at the sixth postoperative month (T6). RESULTS: The study
      included 16 morbidly obese patients. The excretion rate of mannitol was
      significantly lower at T1 compared with T0 and T6 (p = 0.003). There was no
      significant difference in the excretion rates of lactulose or in the
      lactulose/mannitol ratio during the three periods. Six patients (37.5%) exhibited
      a considerable increase in the excretion rate of lactulose at T6 (4-73 times
      higher than the preoperative value), accompanied by proportional variations in
      the lactulose/mannitol ratio. CONCLUSIONS: The significant increase in mannitol
      excretion rate from T1 to T6 most likely reflects the occurrence of intestinal
      adaptation (mucosal hyperplasia), which would tend to minimize the malabsorption
      of macronutrients. A subgroup of patients who undergo RYGB exhibit pronounced
      increase in their intestinal permeability (assessed by the lactulose/mannitol
      ratio and the lactulose excretion rate) at T6.

PMID- 24101088
TI  - Association between liver vitamin A reserves and severity of nonalcoholic fatty
      liver disease in the class III obese following bariatric surgery.
AB  - BACKGROUND: Oxidative stress plays a role in nonalcoholic fatty liver disease
      (NAFLD) pathogenesis and may increase consumption of vitamin A for antioxidant
      purposes. It is hypothesized that drops in vitamin A concentration induce liver
      disease progression and increase hepatocellular carcinoma risk. The aim of this
      study was to assess concentrations of serum and liver retinol in the class III
      obese and correlate them with the histological diagnosis of NAFLD. METHODS: The
      sample group was composed of 68 class III obese (body mass index, BMI >= 40
      kg/m(2)) males and females who underwent bariatric surgery for treating obesity.
      Concentrations of serum and liver retinol were determined using high-performance
      liquid chromatography. The cutoff values used to denote inadequate serum and
      liver retinol stores were <1.05 MUmol/L and <=20 MUg/g, respectively.
      Anthropometric measurements were taken, and NAFLD was diagnosed via histological
      assessment. RESULTS: All the patients had some degree of NAFLD. Inadequate
      concentrations of serum and liver retinol were found in 35.9 and 67.9% of them,
      respectively. A significant association was found between liver retinol
      concentrations and the histological classification of the disease (p < 0.001). No
      such association was found for serum retinol. CONCLUSIONS: This study confirms
      the association between liver retinol and degree of NAFLD, underscoring the need
      for further research in this area, to identify which patients might benefit from
      supplementation of vitamin A.

PMID- 24101090
TI  - Routine trans-abdominal ultrasonography before laparoscopic sleeve gastrectomy:
      the findings.
AB  - Although some bariatric guidelines reserve pre-operative trans-abdominal
      ultrasonography screening for symptomatic patients and those with elevated liver
      enzymes, there has yet to exist a general consensus regarding this issue. Some
      centers still employ its use as a vital step in the workup of the bariatric
      patient. This study aims to observe the prevalent findings on routine pre
      operative trans-abdominal ultrasonography when used as a screening tool prior to
      laparoscopic sleeve gastrectomy (LSG). All patients undergoing LSG were screened
      pre-operatively with trans-abdominal ultrasonography. A retrospective study was
      done of the pre-operative ultrasonography results of patients who underwent LSG
      at Amiri Hospital from 2008 to 2012. A total of 747 patients were included in the
      study, with a median age of 36 (15-68). Five hundred ninety (79.0 %) patients
      were females while 157 (21.0 %) were males, with an overall median body mass
      index (BMI) of 45 (30-90). Two hundred forty patients (32.1 %) had normal pre
      operative ultrasonography results, 83 (11.1 %) were found to have gallstones, 427
      (57.2 %) had fatty liver, and 55 (7.4 %) had other pathologies. There was no
      statistically significant association between BMI and gallstones (p = 0.545) and
      BMI and fatty liver (p = 0.418). Trans-abdominal ultrasonography screening prior
      to LSG revealed a wide range of findings but does not add significant information
      to the pre-operative workup of patients undergoing the procedure and should be
      reserved for indicated patients.

PMID- 24101089
TI  - Controversy surrounding 'mini' gastric bypass.
AB  - Mini gastric bypass is a modification of Mason loop gastric bypass with a longer
      lesser curvature-based pouch. Though it has been around for more than 15 years,
      its uptake by the bariatric community has been relatively slow, and the procedure
      has been mired in controversy right from its early days. Lately, there seems to
      be a surge in the interest in this procedure, and there is now published
      experience with more than 5,000 procedures globally. This review examines the
      major controversial aspects of this procedure against the available scientific
      literature. Surgeons performing this procedure need to be aware of these
      controversies and counsel their patients appropriately. 

PMID- 24101091
TI  - Lack of adherence to follow-up visits after bariatric surgery: reasons and
      outcome.
AB  - BACKGROUND: A substantial number of patients undergoing bariatric surgery are
      lost to follow-up for unknown reasons, which may cause an overestimation of the
      benefits of operation. The aim of this study was to identify the reasons of
      failure to attend controls after bariatric surgery and the relationship with poor
      weight loss. METHODS: A retrospective analysis of a prospective database
      including all patients undergoing bariatric surgery from January 2004 to February
      2012 was performed. Nonadherence was defined as missing any scheduled control
      visit for more than 6 months. Contact was attempted (mail, telephone, and e
      mail), and responders were requested to complete a questionnaire. RESULTS: Forty
      six (17.5%) out of 263 patients were considered nonadherent. Thirty-three (71.7%)
      of these patients completed the questionnaire. The main reasons for nonadherence
      were work- (36.4%) and family-related (18.2%) problems or having moved outside
      the city or to the country (15.2%). The percentage of nonadherent patients aged
      <=45 years was greater as compared with those aged >45 years [28 (60.1%) vs 18
      (42.2%), respectively, P = 0.034]. Likewise, of the 30 patients with unsuccessful
      weight loss (<50% EWL), seven (30.4%) were in the nonadherent group while 23
      (10.6%) in the adherent group (P = 0.046). Finally, 96.9% of patients were
      completely satisfied with surgery and would recommend the procedure to other
      morbid obese patients. CONCLUSION: The nonadherence rate to follow-up visits
      after bariatric surgery was 17.5%, mainly associated with work-related problems.
      Nonadherence was greater in patients aged <=45 years and in those with poor
      weight loss.

PMID- 24101093
TI  - Navifocus WR is the promising intravascular ultrasound for navigating the
      guidewire into true lumen during the coronary intervention for chronic total
      occlusion.
AB  - We describe an initial clinical chronic total occlusion (CTO) case in which CTO
      specific intravascular ultrasound (IVUS): Navifocus WR was useful for navigating
      the second guidewire into the true lumen under the IVUS observation from the
      subintimal space.

PMID- 24101095
TI  - The role of the neurologist in concussions: when to tell your patient to stop.

PMID- 24101094
TI  - Identification of forensically important sarcophagid flies (Diptera:
      Sarcophagidae) in China based on COI and period gene.
AB  - Unequivocal identification of insect specimens is an essential requirement in
      forensic entomology. With the development of molecular identification, spate of
      discussions about the feature of the DNA fragments have been raised. Relying
      solely on single DNA fragment for delimiting closely related species is supposed
      to be dangerous. Aiming at obtaining more reliable markers that might be
      universally used, we explore the utility of 700-bp COI fragment and 678-bp period
      gene fragment in the identification of Sarcophagidae (Diptera). Thirty-six
      sarcophagid fly specimens were collected from 19 locations in 11 Chinese
      provinces. Phylogenetic analysis of the sequenced segments showed that all
      sarcophagid specimens were properly assigned into nine species with relatively
      strong supporting values, which indicated the possibility of separation
      congeneric species with COI and period gene fragments. The difference between
      intraspecific threshold and interspecific divergence confirmed that the
      combination of nuclear and mitochondrial genes for species identification is much
      more accurate. The results of this research will be instrumental for
      implementation of the Chinese Sarcophagidae database. 

PMID- 24101096
TI  - Functional promoter polymorphisms of NFKB1 influence susceptibility to the
      diffuse type of gastric cancer.
AB  - In the present study, we report an association between gastric cancer and
      polymorphisms in NFKB1 (rs28362941 and rs78696119). We employed the PCR-SSCP
      method to detect gene polymorphisms in 479 gastric cancer cases and 880 controls.
      The rs28362941 del/del homozygote was significantly associated with gastric
      cancer development; in particular it was closely associated with diffuse type
      gastric cancer. The rs78696119 GG homozygote was also associated with the diffuse
      type of gastric cancer. In young subjects, both polymorphisms were significantly
      associated with the development of gastric cancer. In addition, both
      polymorphisms were related to tumor progression such as tumor invasion and lymph
      node metastasis. The inflammatory cell infiltration into non-cancerous gastric
      mucosa was greater in the subjects with the rs28362491 del/del or rs78696119 GG
      genotype when compared to those with the other genotypes. In conclusion,
      functional polymorphisms of NFKB1 are associated with an increased risk of
      gastric cancer; in particular they are closely associated with the development of
      diffuse type of gastric cancer via severe gastric inflammation. These
      polymorphisms also appear to be associated with gastric cancer progression.

PMID- 24101097
TI  - Differential BCCIP gene expression in primary human ovarian cancer, renal cell
      carcinoma and colorectal cancer tissues.
AB  - Human BCCIP, a protein which interacts with BRCA2 and CDKN1A (Cip1, p21), has
      been implicated in many cellular processes including cell cycle regulation, DNA
      recombination and damage repair, telomere maintenance, embryonic development and
      genomic stability. BCCIP gene expression, which is an important BRCA2 cofactor in
      tumor suppression, has been identified in some primary cancers. Thus, we
      investigated the role of BCCIP expression in a large sample of clinically
      diagnosed primary ovarian cancer, renal cell carcinoma (RCC) and colorectal
      cancer (CRC) tissues. Using clinically diagnosed frozen primary cancer tissues,
      quantitative PCR (qPCR), western blot analysis (WB) and immunohistochemical
      staining (IHC) approaches were used to detect and measure gene expression.
      Reduced BCCIP gene expression in ovarian cancer, RCC and CRC tissues occurred in
      74, 89 and 75% of tissue samples, respectively. qPCR analysis of mRNA expression
      in 54 ovarian cancer, 50 RCC and 44 CRC samples revealed significant (>2-fold
      decreased) BCCIP downregulation in 56, 70 and 46% of tissue samples,
      respectively. Although BCCIP expression in three different tumor tissues
      decreased, the relationship between BCCIP expression and clinicopathological
      features of each cancer was distinct. Compared to normal tissues, BCCIP
      expression in ovarian cancers was significantly downregulated in serous,
      endometrioid and mucinous carcinomas. Downregulation of BCCIP expression was
      strongly associated with clear cell RCC (ccRCC) and Fuhrman tumor grading, but
      significant differences in BCCIP expression between CRC and matched normal
      tissues occurred only in male CRC tissues (p<0.05) and in tissue with a T4 tumor
      stage (p<0.01). Thus, BCCIP protein was chiefly reduced in ovarian cancer and RCC
      tissue samples (p<0.05). BCCIP gene expression was downregulated in human ovarian
      cancer, RCC and CRC tissues, suggesting a role for the gene in the pathogenesis
      of these cancers.

PMID- 24101098
TI  - Postoperative venous thromboembolic disease: prevention, public reporting, and
      patient protection.

PMID- 24101099
TI  - Dynamics of parent-adolescent communication on sexual health and HIV/AIDS in
      Tanzania.
AB  - Communication between parents and their adolescent children has been identified
      as one of the potential protective factors for adolescent sexual health.
      Qualitative exploration of sexual health communication with adolescents aged 12
      15 (N = 114) and a sub-group of the parents (N = 20) was carried out. Four major
      themes emerged: reasons for parent-adolescent communications, or lack thereof;
      the focus of parental messages; the moral of the message; and the barriers to
      communication between parents and adolescents. Findings revealed similarities and
      discrepancies in views and perceptions between parents and adolescents.
      Adolescents and parents suggested that some sexual health communication was
      happening. Parents were reportedly likely to use fear to ensure that their
      children do not engage in risky sexual activities, while adolescents reported
      that conversations with their parents were mostly ambiguous and filled with
      warnings about the dangers of HIV/AIDS. Several communication barriers were
      reported by parents and adolescents. Parents of adolescents would benefit from
      HIV/AIDS specific communication skills. 

PMID- 24101100
TI  - Different dimensions of HIV-related stigma may have opposite effects on hiv
      testing: evidence among young men and women in South Africa.
AB  - Although HIV-related stigma in general is known to deter HIV-testing, the extent
      to which different dimensions of stigma independently influence testing behaviour
      is poorly understood. We used data on young black men (n = 553) and women (n =
      674) from the 2009 Cape Area Panel Study to examine the independent effects of
      stigmatising attitudes, perceived stigma and observed enacted stigma on HIV
      testing. Multivariate logistic regression models showed that stigma had a strong
      relationship with HIV-testing among women, but not men. Women who held
      stigmatising attitudes were more likely to have been tested (OR 3, p < 0.01),
      while perceived stigma (OR 0.61, p < 0.1) and observed enacted stigma (OR 0.42, p
      < 0.01) reduced the odds significantly of women having had an HIV test. Our
      findings highlight that different dimensions of stigma may have opposite effects
      on HIV testing, and point towards the need for interventions that limit the
      impact of enacted and perceived stigma on HIV-testing among women.

PMID- 24101102
TI  - Prevention: Polypills for cardiovascular prevention: a step forward?
AB  - The effect of a fixed-dose combination drug strategy ('polypill') on patients'
      adherence to medication was analysed in a series of 2,004 individuals with, or at
      high risk of, cardiovascular disease in the UMPIRE study. The polypill improved
      adherence by >20%, but the reduction in blood-pressure and cholesterol levels was
      modest.

PMID- 24101101
TI  - Mechanisms and management of TAVR-related complications.
AB  - Patients with severe aortic stenosis who are at high surgical risk or not
      considered to be suitable candidates for surgical aortic valve replacement are
      increasingly being treated with transcatheter aortic valve replacement (TAVR).
      Although this novel treatment modality has been proven to be effective in this
      patient population, serious complications occur in approximately one-third of
      patients during the month after the procedure. Such events include myocardial
      infarction, cerebrovascular events, vascular complications, bleeding, acute
      kidney injury, valve regurgitation, valve malpositioning, coronary obstruction,
      and conduction disturbances and arrhythmias, which can all lead to death.
      Prevention of these complications should be based on patient screening and
      selection by a dedicated 'heart team' and the use of multimodality imaging.
      Anticipation and early recognition of these complications, followed by prompt
      management using a wide range of percutaneous or surgical rescue interventions,
      is vital to patient outcome. Continuous patient assessment and reporting of
      complications according to standardized definitions, in addition to growing
      operator experience and upcoming technological refinements, will hopefully reduce
      the future rate of complications related to this procedure.

PMID- 24101104
TI  - Identification of CD90 as a marker for lung cancer stem cells in A549 and H446
      cell lines.
AB  - Accumulating evidence supports that cancer stem cells (CSCs) are responsible for
      tumor initiation, progression, distal metastasis and even drug resistance.
      Although CD90 has been identified as a marker for several types of stem cells,
      such as liver CSCs, the potential role of CD90 as a marker for lung CSCs has yet
      to be fully characterized. Our previous study demonstrated that the lung cancer
      stem-like cells isolated from A549 tumor spheres, which were cultured in serum
      free conditioned medium, had stronger proliferation and self-renewal abilities,
      and expressed higher levels of the stem cell markers Sox2 and Oct4 as compared to
      A549 adherent cells. In the present study, we identified CD90 as a novel surface
      marker of CSCs in lung cancer cells. Furthermore, we isolated CD90+ CSCs from
      lung cancer cell lines A549 and H446. Our results revealed that the CD90+ cells,
      but not the CD90- cells, from lung cancer cells displayed higher tumorigenic
      capacity. These findings suggest that CD90 could be a potential marker of lung
      CSCs and thus provide new insight into further therapeutic strategies of lung
      cancer. 

PMID- 24101105
TI  - Using barriers analysis to refine a novel model of neurocritical care.
AB  - BACKGROUND: In order to deliver specialized neurocritical care (NCC) without a
      dedicated neurological intensive care unit (ICU), we established a virtual NCC
      unit within an existing mixed level III ICU. This initiative required changes to
      patient allocation, physician staffing, and care protocols. In advance of its
      implementation, we gaged readiness, assessed barriers, and solicited feedback
      from staff. METHODS: Clinicians at our academic hospital and trauma centre in
      Toronto, Ontario were the subjects of this concurrent mixed methods study.
      Eighteen stakeholders were individually interviewed. 116 of 217 eligible ICU
      staff participated in the survey and 36 staff attended the focus group sessions.
      RESULTS: From the survey, the most significant barriers to this reorganization
      were staff anxiety about coping (28 %) and a concern that patients would not
      receive better care (24 %). Noteworthy obstacles about the use of protocols were
      their lack of flexibility (19 %) and that implementation was seen as impractical
      (16 %). Seventeen barriers were proposed through an open-ended survey question.
      Content analysis revealed general resistance, educational challenges, workflow
      adjustment to a diagnosis-based rounding pattern and coordination conflicts to be
      the central barriers. These findings were confirmed in focus group discussions,
      with a lack of resources as an additional important challenge. CONCLUSIONS: A new
      workable model for NCC has been developed, facilitated by this analysis. Steps to
      overcome barriers demonstrated in this study include additional educational
      measures, changes to the rounding protocols, and patient allocation algorithms.

PMID- 24101106
TI  - Mesoporous (ZnO)(x)(MgO)(1-x) nanoplates: template-free solvothermal synthesis,
      optical properties, and their applications in water treatment.
AB  - Mesoporous (ZnO)x(MgO)1-x nanoplates were synthesized from a solution containing
      zinc acetate and magnesium acetate by a template-free solvothermal synthetic
      method followed by subsequent calcination. After thermal treatment, the plate
      like morphology was retained. The formation of pores was due to thermal
      decomposition of Mg(OH)2 and the release of H2O. The optical properties of the
      mesoporous (ZnO)x(MgO)1-x nanoplates had been investigated by UV-vis absorption
      and cathodoluminescence (CL) emission spectroscopy. The UV-vis absorption spectra
      showed the band gap variation of the as-prepared samples due to the presence of
      ZnO in the MgO nanostructures. The CL spectra showed strong broad peaks in the
      visible range from 450 to 700 nm, indicating significant oxygen vacancy defects
      on the surface of the (ZnO)x(MgO)1-x nanoplates. Moreover, the samples were
      evaluated as photocatalysts for the UV-induced degradation of methyl orange (MO)
      in aqueous solution. The (ZnO)x(MgO)1-x nanoplates showed high photocatalytic
      performance and thus would be promising candidates for polluted water treatment. 

PMID- 24101107
TI  - The relationship between fibroblast growth factor 23 and osteoporosis in
      postmenopausal women.
AB  - AIM: A lack of estrogen in postmenopausal women is an important factor causing
      the development of osteoporosis. Our purpose is to investigate the effects of
      Fibroblast Growth Factor 23 (FGF-23) on bone mineral metabolism and bone
      turnover. METHODS: Twenty-eight patients with postmenopausal osteoporosis (PMO),
      32 patients with postmenopausal osteopenia and 30 healthy control subjects
      (postmenopausal non-osteoporosis) were included in this study. In order to assess
      the bone mineral metabolism; FGF 23, parathyroid hormone, vitamin D, calcium,
      phosphate, osteocalcin, alkaline phosphatase and hydroxyproline levels were
      measured. RESULTS: FGF 23 levels were found significantly higher in PMO group
      compared with postmenopausal osteopenia and control groups (P<0.01 and P<0.05
      respectively). Urine hydroxyproline level was detected to be significantly lower
      in PMO patients compared with control group (P<0.01). Lomber and femur BMD levels
      were found to be significantly lower in PMO patients compared with postmenopausal
      osteopenia and control groups (P<0.001, P<0.001; P<0.001, P<0.001 respectively).
      On the other hand, when we categorized the PMO group subjects according to the
      age of menopause, the FGF 23 levels were found to be significantly higher in the
      group of menopausal age <5 years compared to the group of menopausal age >10 and
      to the group of menopausal age 5-10 years (P<0.05, P<0.05). CONCLUSION: We think
      our findings indicate that serum FGF 23 level is a significant determinant of
      increased bone turnover at early periods in PMO patients.

PMID- 24101108
TI  - Effect of endothelin inhibition on lung fibroblasts on patients with systemic
      sclerosis.
AB  - AIM: The aim of the study was to investigate the effect of selective ETRA
      Sitaxsentan on viability and differentiation into myofibroblasts of lung
      fibroblasts derived from SSc-ILD patients and the ability of this drug to modify
      the lung fibroblast synthesis of VEGF, type I collagen and fibronectin. METHODS:
      Primary human lung fibroblast cultures were obtained from BAL of SSc-ILD
      patients. Cell cultures were exposed for 48 h to crescent concentrations of
      Sitaxsentan (10 -6M to 10 -4M). In these experimental conditions we evaluated
      cell viability through crystal violet staining, the production and mRNA
      expression of VEGF, fibronectin and type I collagen respectively through ELISA
      and real-Time PCR. Further, we detected alpha-Smooth Muscle Actin (alpha-SMA)
      through immunocytochemical assay. RESULTS: The lowest concentration of
      sitaxsentan (10-6M) did not affect fibroblasts viability; conversely at higher
      concentrations, sitaxsentan induced a significant inhibition of cell viability.
      Synthesis and mRNA expression of VEGF, type 1 collagen and fibronectin were
      significantly reduced in treated lung fibroblasts compared to the untreated ones,
      in a dose-dependent manner. At higher concentrations, Sitaxsentan reduced the
      expression of alpha-SMA. CONCLUSION: The results of this study show that
      sitaxentan is able in vitro to reduce both cell viability than production of VEGF
      and extra-cellular matrix components in SSc lung fibroblasts, confirming the anti
      fibrotic potential of ETRA in SSc. The decreased expression of alpha-SMA in
      treated cells indicate that sitaxsentan may inhibit the fibroblast
      differentiation toward a myo-fibroblast phenotype and further support the
      hypothesis that the selective ETRAs may be beneficial in patients with SSc-ILD as
      anti fibrotic agents.

PMID- 24101109
TI  - Isolation of rabbit bone marrow mesenchymal stem cells using density gradient
      centrifugation and adherence screening methods.
AB  - AIM: Under special conditions, bone marrow mesenchymal stem cells (BMSCs) can
      differentiate into osteoblasts and chondroblasts. However, MSCs are few in bone
      marrow. How to harvest, purify and rapidly proliferate in vitro is a foundation
      of application in tissue engineering technique. To optimize, collect, purify,
      assess rabbit BMSCs and to observe the biological character of BMSCs. METHODS:
      Two female New Zealand rabbits aged 2 months were used for MSC collection and
      primary culture. Bone marrow solution was purified by density gradient
      centrifugation and adherence screening method. Culture solution was obtained.
      BMSCs were incubated in phosphate buffered solution (PBS), supplemented with 2.5
      g/L trypsin (3.0 mL), and placed in an incubator at 37  degrees C for two or
      three minutes. Cell morphology was observed using an inverted microscope. The
      digestion was stopped when cytoplasm recovery, long and thin cells with large
      intercellular space, and few round cells appeared. Subsequently, BMSCs were
      incubated in serum-free L-DMEM, and placed in a plastic culture flask at
      1.0*108/L. MSC morphology, ultrastructure and surface marker; proliferation of
      the first, third, fifth, eighth and tenth passages of BMSCs; cell growth curve
      was drawn. BMSCs was pure following density gradient centrifugation and adherence
      screening method. The third and fifth passage of cells had typical whirlpool
      shape. RESULTS AND CONCLUSION: Transmission electron microscope demonstrated that
      round or oval MSCs possessed large nuclei, big nucleus proportion, a few cellular
      organ. These were low-differentiated cells. Growth curve of cultured MSCs was "S"
      shape. The first, third and fifth passage cells had strong reproductive
      capability. The eighth and tenth passage of cells had significantly reduced
      proliferation. Cells isolated were positive for CD44 and CD90, but negative for
      CD34. These were low-differentiated cells under the electron microscope. Isolated
      cells are MSCs, with the property of stem cells. The third and fifth passage
      cells are pure, with strong reproductive capability.

PMID- 24101110
TI  - Maternal and cord blood apelin, resistin and visfatin levels in gestational
      diabetes mellitus.
AB  - AIM: The aim of this paper was to investigate maternal and cord blood apelin,
      resistin and visfatin concentrations in pregnant women with and without
      gestational diabetes mellitus (GDM). METHODS: This case-control study was
      conducted on 24 women with GDM and 21 women without GDM. Maternal plasma and cord
      blood apelin, resistin and visfatin levels were measured with ELISA. RESULTS: The
      cord blood apelin levels were significantly lower in women with GDM than control
      subjects (111.23+/-31.53 vs.. 257.48+/-133.97 pg/mL, P=0.002). However, the
      decrease of maternal apelin levels in GDM group was not statistically significant
      (140.76+/-48.38 vs. 163.53+/-91.12 pg/mL, P=0.602). Women with GDM had lower
      maternal and cord blood visfatin concentrations and higher resistin
      concentrations than control group. Maternal resistin concentrations were
      significantly correlated with HOMA-IR (r=0.745, P=0.005). The apelin and visfatin
      levels did not correlate with HbA1c, BMI, HOMA-IR, glucose and birth weight.
      CONCLUSION: GDM is associated with lower cord blood apelin levels than control
      subjects. GDM appears to influence fetoplacental apelin metabolism. Apelin may
      not be directly involved in the regulation of maternal insulin sensitivity. Our
      results indicate that there is an increase in resistin concentrations and a
      decrease in visfatin concentrations in maternal serum and cord blood serum with
      GDM.

PMID- 24101111
TI  - Takotsubo cardiomyopathy: real life management in the intensive coronary care
      unit.
AB  - AIM: Takotsubo cardiomyopathy is a cardiac syndrome characterized by reversible
      left ventricular dysfunction, ischemic changes on electrocardiogram, elevation of
      cardiac biomarkers, absence of obstructive coronary artery disease in the setting
      of various stressing conditions. To date, little is known on best clinical
      management of this syndrome in coronary care units. Whe thus aimed to present our
      experience in a real life takotsubo population. METHODS: We identified all
      patients with Takotsubo cardiomyopathy at our center Maria Vittoria Hospital,
      Turin, between October 2006 and February 2012. Patients where considered to have
      Takotsubo syndrome if they presented chest pain on admission, new
      elettrocardiographic changes suggestive of myocardial ischemia, evidence of
      apical balloning with hyperkinesis of basal segments on echocardiography, rise in
      troponin I and, after coronary angiography, no coronary artery disease. We
      adjudicated the following clinical events: death and recurrence of ischemic
      events; we also made a detailed analysis of the stressing conditions leading to
      clinical syndrome. RESULTS: A total of 26 patients were included, 4 (15%) males
      and 22 (85%) females; mean age was 71+/-13. After more than 1 year median follow
      up the incidence of death was 7.7% (2 deaths), with all deaths, due to
      cardiogenic shock, occurring in the first 10 days of hospitalization; 2 patients
      (8%) experienced recurrence of ischemic event. Leading cause of Takostubo was
      major depressive episode (16%), followed by mourning (12%), falling down with
      difficulties in standing up (12%), vomiting (8%) and pulmonary infection (8%). In
      the coronary care unit major complications of patients with Takotsubo syndrome
      were acute hearth failure (62%), cardiogenic shock (27%), sepsis (31%), pulmonary
      aedema (27%) and anemia (12%). Two patients needed non-invasive ventilation
      support and one intra-aortic balloon conterpulasation. In addition one patient
      developed rabdomyolysis and one left heart thrombus. Cornerstone drug therapy was
      as follows: 96% of patients took aspirin, 58% beta blockers, 54% nitroglicerine,
      46% intravenous heparin, 27% dopamine. CONCLUSION: Takotsubo syndrome is an
      important safety issue occurring predominantly in post-menopausal women
      undergoing specific stressing condition. Heart failure and cardiogenic shock are
      the most serious clinical complication and leading cause of death in the short
      period, good prognosis is seen thereafter.

PMID- 24101112
TI  - Medical treatment of hepatocellular carcinoma.
AB  - The management of hepatocellular carcinoma (HCC) has substantially changed in the
      past few decades, the introduction of novel therapies (such as sorafenib) have
      improved patient survival. Nevertheless, HCC remains the third most common cause
      of cancer-related deaths worldwide. Decision-making largely relies on evidence
      based criteria, as showed in the US and European clinical practice guidelines,
      which endorse five therapeutic recommendations: resection; transplantation;
      radiofrequency ablation; chemoembolization; and sorafenib. However, areas still
      exist in which uncertainty precludes a strong recommendation, such as the role of
      adjuvant therapies after resection, radioembolization with yttrium-90 or second
      line therapies for advanced HCC. Many clinical trials that are currently ongoing
      aim to answer these questions. The first reported studies, however, failed to
      identify novel therapeutic alternatives (that is, sunitinib, erlotinib or
      brivanib). Efforts that focus on the implementation of personalized medicine
      approaches in HCC will probably dominate research in the next decade. 

PMID- 24101113
TI  - [Venous thromboembolism in pregnancy: current state of the art].
AB  - Venous thromboembolism (VTE) is a major cause of maternal morbidity and mortality
      during pregnancy or early after delivery and it remains a diagnostic and
      therapeutic challenge. The latest Confidential Enquiry into Maternal Deaths (2006
      2008) showed that VTE is now the third leading cause of direct maternal
      mortality, beside sepsis and hypertension. In particular the prevalence of VTE
      has been estimated to be 1 per 1000-2000 pregnancies. The risk of VTE is five
      times higher in a pregnant woman than in non-pregnant woman of similar age and
      postpartum VTE is more common than antepartum VTE. A literature search was
      carried out on Pubmed using the following key words: "venous thromboembolism",
      "pregnancy", "risk factors", "prophylaxis", "anticoagulants". Studies from 1999
      onwards were analyzed. This review aimed to provide an update of whole current
      literature on VTE in pregnancy highlighting the most recent findings in
      diagnostic and therapeutic strategies, considering in detail risks and benefits
      of various techniques and drug classes, for both mother and fetus. Large trials
      of anticoagulants administration in pregnancy are lacking and recommendations are
      mainly based on case series and on expert opinions. Nonetheless, anticoagulants
      are believed to improve the outcome of pregnancy for women with current or
      previous VTE. 

PMID- 24101114
TI  - Ulcerative colitis and systemic lupus erythematosus.

PMID- 24101115
TI  - Therapy-related acute myeloblastic leukemia after splenectomy in a patient with
      composite lymphoma developing after treatment of chronic lymphocytic leukemia.

PMID- 24101116
TI  - Facile aqueous synthesis of beta-AgI nanoplates as efficient visible-light
      responsive photocatalyst.
AB  - Owing to far-ranging industrial applications and theoretical researches, tailored
      synthesis of well-defined nanocrystals has attracted substantial research
      interest. Herein, beta-AgI nanoplates have been synthesized through a facile
      polyvinylpyrrolidone (PVP)-assisted-aqueous-solution (PAAS) method under mild
      conditions. The parametric studies on the effect of ratio of reactants, solvents
      and surfactants were performed, revealing that a molar ratio of I(-) to Ag(+) of
      1.2 in deionized water and the presence of appropriate PVP as stabilizing agent
      can stimulate the preferred orientation growth of AgI nanoplates. The as
      synthesized AgI nanoplates exhibit excellent photocatalytic activity and enhanced
      durability towards the degradation of organics, i.e., rhodamine B (RhB), under
      visible light illumination in comparison with corresponding bulk nanoparticles. A
      possible photocatalytic reaction mechanism was discussed, revealing O2(-) and
      h(+) are main reactive species and free OH radicals in solution also contribute
      to the degradation reaction. The superior photocatalytic performance renders the
      as-achieved AgI nanoplates promising candidates for applications in the fields of
      environmental purification or water disinfection. The present work opens an
      avenue to the synthesis of other shaped silver halide nanophotocatalysts. 

PMID- 24101117
TI  - The Rao's Brief Repeatable Battery version B: normative values with age,
      education and gender corrections in an Italian population.
AB  - The Brief Repeatable Battery (BRB) of Neuropsychological Tests is one of the most
      widely used instruments to assess cognitive functioning in multiple sclerosis
      patients. However, to date, normative data for the Italian population are
      available only for the version A, which limits the use of the battery in
      longitudinal evaluations. We administered the BRB version B to 132 healthy
      subjects to obtain normative values taking into account the influences of
      demographic factors on the test scores and calculating corrections for these
      relevant factors (age, gender and education). Higher age and educational level
      were associated with better performance on all the tests. The World List
      Generation was also influenced by gender, since women performed better than men.
      Moreover, some tests of the version B seem to be easier than those of version A.
      Our data can improve the applicability of the BRB for both clinical and research
      purposes in longitudinal assessments. 

PMID- 24101118
TI  - Risk of major adverse cardiac events following noncardiac surgery in patients
      with coronary stents.
AB  - IMPORTANCE: Guidelines recommend delaying noncardiac surgery in patients after
      coronary stent procedures for 1 year after drug-eluting stents (DES) and for 6
      weeks after bare metal stents (BMS). The evidence underlying these
      recommendations is limited and conflicting. OBJECTIVE: To determine risk factors
      for adverse cardiac events in patients undergoing noncardiac surgery following
      coronary stent implantation. DESIGN, SETTING, AND PARTICIPANTS: A national,
      retrospective cohort study of 41,989 Veterans Affairs (VA) and non-VA operations
      occurring in the 24 months after a coronary stent implantation between 2000 and
      2010. Nonlinear generalized additive models examined the association between
      timing of surgery and stent type with major adverse cardiac events (MACE)
      adjusting for patient, surgery, and cardiac risk factors. A nested case-control
      study assessed the association between perioperative antiplatelet cessation and
      MACE. MAIN OUTCOMES AND MEASURES: A composite 30-day MACE rate of all-cause
      mortality, myocardial infarction, and cardiac revascularization. RESULTS: Within
      24 months of 124,844 coronary stent implantations (47.6% DES, 52.4% BMS), 28,029
      patients (22.5%; 95% CI, 22.2%-22.7%) underwent noncardiac operations resulting
      in 1980 MACE (4.7%; 95% CI, 4.5%-4.9%). Time between stent and surgery was
      associated with MACE (<6 weeks, 11.6%; 6 weeks to <6 months, 6.4%; 6-12 months,
      4.2%; >12-24 months, 3.5%; P < .001). MACE rate by stent type was 5.1% for BMS
      and 4.3% for DES (P < .001). After adjustment, the 3 factors most strongly
      associated with MACE were nonelective surgical admission (adjusted odds ratio
      [AOR], 4.77; 95% CI, 4.07-5.59), history of myocardial infarction in the 6 months
      preceding surgery (AOR, 2.63; 95% CI, 2.32-2.98), and revised cardiac risk index
      greater than 2 (AOR, 2.13; 95% CI, 1.85-2.44). Of the 12 variables in the model,
      timing of surgery ranked fifth in explanatory importance measured by partial
      effects analysis. Stent type ranked last, and DES was not significantly
      associated with MACE (AOR, 0.91; 95% CI, 0.83-1.01). After both BMS and DES
      placement, the risk of MACE was stable at 6 months. A case-control analysis of
      284 matched pairs found no association between antiplatelet cessation and MACE
      (OR, 0.86; 95% CI, 0.57-1.29). CONCLUSIONS AND RELEVANCE: Among patients
      undergoing noncardiac surgery within 2 years of coronary stent placement, MACE
      were associated with emergency surgery and advanced cardiac disease but not stent
      type or timing of surgery beyond 6 months after stent implantation. Guideline
      emphasis on stent type and surgical timing for both DES and BMS should be
      reevaluated.

PMID- 24101119
TI  - Appropriate chemotherapy dosing in obese patients with cancer.

PMID- 24101120
TI  - Suitable trial designs and cohorts for preventive breast cancer agents.
AB  - Effective chemoprevention of oestrogen receptor (ER)-positive breast cancer has
      been shown convincingly using several selective ER modulators and the aromatase
      inhibitor exemestane. Although these agents are well tolerated and the numbers
      needed-to-treat in the prevention setting are similar to other established
      preventive interventions, uptake has been poor in clinical practice because of
      difficulties in visualizing risk, predicting individual outcomes and measuring
      treatment benefit. In addition, new agents targeting ER-negative breast cancer
      are urgently needed. The development of new agents is hampered by the lack of
      suitable biomarkers and targets, as well as regulatory and financial
      considerations. Establishing breast cancer chemoprevention in standard clinical
      practice will require advances in many different fields, including biomarker
      research, the development of more powerful tools to predict and communicate the
      risks and benefits of treatments and establishing innovative trial designs.
      Furthermore, changes in regulatory procedures could reduce the size and cost of
      trials needed in the prevention setting. Identification of biomarkers for risk
      and efficacy that are easily accessible, such as blood-based biomarkers, will be
      key to future chemoprevention strategies. 

PMID- 24101121
TI  - Haematological cancer: a step before the next leap?

PMID- 24101122
TI  - Genetics: genomic alteration profiles across different cancer types.

PMID- 24101123
TI  - Innovation: London Cancer-multidisciplinary approach to urological cancer.

PMID- 24101124
TI  - Sarcopenia and chemotherapy dosing in obese patients.

PMID- 24101125
TI  - Effect of Pluchea lanceolata bioactives in LPS-induced neuroinflammation in C6
      rat glial cells.
AB  - Neuroinflammation plays a significant role in various chronic and acute
      pathological conditions of the central nervous system. In the Indian system of
      medicine, Pluchea lanceolata is used to treat the neurological disorders. We
      investigated the effect of major pentacyclic triterpene and its naturally
      occurring acetate derivative isolated from P. lanceolata on lipopolysaccharide
      (LPS)-stimulated neuroinflammatory condition associated to inflammatory cytokine
      production in rat astrocytoma cell line (C6). The log concentration dependence of
      Pluchea bioactive taraxasterol (Tx) significantly (p < 0.05) attenuates the
      release of pro-inflammatory cytokines, such as TNF-alpha, IFN-gamma, and IL-6,
      while its in situ produced acetyl derivative, i.e., taraxasterol acetate (TxAc),
      did not inhibit the LPS-induced IL-6 production at lower concentration (p >
      0.05). Surflex-Dock molecular modeling study was performed to simulate the
      binding capacity of compounds into the active site of the TNF-alpha (2AZ5), tumor
      protein P53 (2VUK), and NF-kappa-B (1RAM). The differential inhibition of
      cytokines by Tx and TxAc was further confirmed by high docking scores showing the
      high affinity to target proteins. Findings of the study demonstrated the
      comparatively greater role of Pluchea triterpene than its in situ produced
      acetate derivate in neuroinflammation-associated disorders. 

PMID- 24101126
TI  - Intradermal immunization with combined baculovirus and tumor cell lysate induces
      effective antitumor immunity in mice.
AB  - Although tumor lysate contains all the potential helper and killer epitopes
      capable of stimulating T cells, it is difficult to use as a cancer vaccine
      because it suppresses dendritic cell (DC) function. We report that wild-type
      baculovirus possesses an adjuvant effect to improve the immunogenicity of tumor
      lysate. When mice were administered CT26 tumor cell lysate combined with
      baculovirus intradermally, antitumor immunity was induced and rejection of CT26
      tumor growth was observed in 40% of the immunized mice. In contrast, such
      antitumor immunity was not elicited in mice inoculated with tumor cell lysate or
      baculovirus alone. In tumor-bearing mice, which had previously received the
      combined baculovirus and tumor lysate vaccine, the established tumors were
      completely eradicated by administering a booster dose of the combined vaccine.
      This antitumor effect was attributed to tumor-specific T cell immunity mediated
      primarily by CD8+ T cells. Baculovirus also strongly activated DCs loaded with
      tumor lysate. Increased interleukin (IL)-6 and IL-12p70 production were also
      observed in DCs co-cultured with tumor cell lysate and baculovirus. Our study
      demonstrates that combined baculovirus and tumor lysate vaccine can effectively
      stimulate DCs to induce acquired antitumor immunity.

PMID- 24101127
TI  - DcR3 regulates the growth and metastatic potential of SW480 colon cancer cells.
AB  - Decoy receptor 3 (DcR3) is considered to have anti-apoptotic and pro-metastatic
      functions, suggesting it might be a therapeutic target. We examined the role and
      mechanisms of DcR3 on growth and the metastatic ability of SW480 colon cancer
      cells to provide therapeutic information for targeting DcR3 by RNA interference
      (RNAi) technology. Growth and the metastatic ability were inhibited, apoptosis
      was induced and cell cycle profile was changed after decreasing DcR3 expression,
      with lower levels of vascular endothelial growth factors (VEGFs) and matrix
      metalloproteinases (MMPs) expression. Our results implied the therapeutic
      potential of silencing DcR3 expression by RNAi in colon cancer.

PMID- 24101128
TI  - Physiological variation of segmented OCT retinal layer thicknesses is short
      lasting.
AB  - The application of spectral domain optical coherence tomography as a surrogate
      for neurodegeneration in a range of neurological disorders demands better
      understanding of the physiological variation of retinal layer thicknesses, which
      may mask any value of this emerging outcome measure. A prospective study compared
      retinal layer thicknesses between control subjects (n = 15) and runners (n = 27)
      participating in a 10-km charity run. Three scans were performed using an eye
      tracking function (EBF) and automated scan registration for optimal precision at
      (1) baseline, (2) directly after the run, and (3) following a rehydration period.
      Retinal layer segmentation was performed with suppression of axial retinal vessel
      signal artifacts. Following the run, there was an increase in the relative
      retinal nerve fibre layer (p = 0.018), the combined inner plexiform/ganglion cell
      layer (p = 0.038), and the outer nuclear layer (p = 0.018) in runners compared to
      controls. The initial increase of thickness in the outer nuclear layer of runners
      (p < 0.0001) was likely related to (noncompliant) rehydration during exercise.
      Following a period of rest and rehydration, the difference in thickness change
      for all retinal layers, except the retinal nerve fibre layer (RNFL) (p < 0.05),
      disappeared between the two groups. There is a quantifiable change in the axial
      thickness of retinal layersthat which can be explained by an increase in the
      cellular volume. This effect may potentially be caused by H2O volume shifts.

PMID- 24101129
TI  - Ultrasound of inherited vs. acquired demyelinating polyneuropathies.
AB  - We compared features of nerve enlargement in inherited and acquired demyelinating
      neuropathies using ultrasound. We measured median and ulnar nerve cross-sectional
      areas in proximal and distal regions in 128 children and adults with inherited
      [Charcot-Marie-Tooth-1 (CMT-1) (n = 35)] and acquired [chronic inflammatory
      demyelinating polyneuropathy (CIDP) (n = 55), Guillaine-Barre syndrome (GBS) (n =
      21) and multifocal motor neuropathy (MMN) (n = 17)] demyelinating neuropathies.
      We classified nerve enlargement by degree and number of regions affected. We
      defined patterns of nerve enlargement as: none, no enlargement; mild, nerves
      enlarged but never more than twice normal; regional, nerves normal in at least
      one region and enlarged more than twice normal in at least one region; diffuse,
      nerves enlarged at all four regions with at least one region more than twice
      normal size. Nerve enlargement was commonly diffuse (89 %) and generally more
      than twice normal size in CMT-1, but not (p < 0.001) in acquired disorders which
      mostly had either no, mild or regional nerve enlargement [CIDP (64 %), GBS (95
      %), and MMN (100 %)]. In CIDP, subjects treated within 3 months of disease onset
      had less nerve enlargement than those treated later. Ultrasound identified
      patterns of diffuse nerve enlargement can be used to screen patients suspected of
      having CMT-1. Normal, mildly, or regionally enlarged nerves in demyelinating
      polyneuropathy suggests an acquired etiology. Early treatment in CIDP may impede
      nerve enlargement.

PMID- 24101130
TI  - Diagnostic hallmarks and pitfalls in late-onset progressive transthyretin-related
      amyloid-neuropathy.
AB  - Familial amyloid polyneuropathy (FAP) is a progressive systemic autosomal
      dominant disease caused by pathogenic mutations in the transthyretin (TTR) gene.
      We studied clinical, electrophysiological, histopathological, and genetic
      characteristics in 15 (13 late-onset and two early-onset) patients belonging to
      14 families with polyneuropathy and mutations in TTR. In comparison, we analysed
      the features of nine unrelated patients with an idiopathic polyneuropathy, in
      whom TTR mutations have been excluded. Disease occurrence was familial in 36 % of
      the patients with TTR-associated polyneuropathy and the late-onset type was
      observed in 86 % (mean age at onset 65.5 years). Clinically, all late-onset TTR
      mutant patients presented with distal weakness, pansensory loss, absence of deep
      tendon reflexes, and sensorimotor hand involvement. Afferent-ataxic gait was
      present in 92 % leading to wheelchair dependence in 60 % after a mean duration of
      4.6 years. Autonomic involvement was observed in 60 %, and ankle edema in 92 %.
      The sensorimotor polyneuropathy was from an axonal type in 82 %, demyelinating or
      mixed type in 9 % each. Compared to the TTR-unmutated idiopathic polyneuropathy
      patients, we identified rapid progression, early ambulatory loss, and autonomic
      disturbances, associated with a severe polyneuropathy as red flags for TTR-FAP.
      In 18 % of the late-onset TTR-FAP patients, no amyloid was found in nerve
      biopsies. Further diagnostic pitfalls were unspecific electrophysiology, and
      coincident diabetes mellitus (23 %) or monoclonal gammopathy (7 %). We conclude
      that a rapid disease course, severely ataxic gait, hand involvement, and
      autonomic dysfunction are diagnostic hallmarks of late-onset TTR-FAP. Genetic
      analysis should be performed even when amyloid deposits are lacking or when
      polyneuropathy-causing comorbidities are concomitant.

PMID- 24101131
TI  - Menopause in multiple sclerosis: therapeutic considerations.
AB  - While the onset of multiple sclerosis (MS) typically occurs during the
      childbearing years, many women living with MS are of perimenopausal age. There is
      frequent overlap between menopausal and MS-related symptoms and co-morbidities
      (e.g. sexual dysfunction, mood disorders and bladder function). Furthermore, some
      MS symptoms may be exacerbated by perimenopausal changes such as hot flashes or
      sleep disturbance. The MS neurologist may frequently be the first to become aware
      of these symptoms and to play a role in monitoring and managing them. In this
      review, we describe immunological and neurologic changes at menopause as they may
      impact MS. We then review common symptoms, including fatigue, depression, sexual
      function, pain and insomnia, and provide both behavioral and pharmacological
      suggestions for their management. Next, we discuss the need for osteoporosis and
      cancer screening in perimenopausal women with MS. Finally, we highlight important
      research gaps, including what effect, if any, the menopausal transition may play
      on MS disease course as well as the potential modulatory role of hormone
      replacement therapies. 

PMID- 24101132
TI  - Progressive ataxia with oculo-palatal tremor and optic atrophy.

PMID- 24101133
TI  - IQGAP1 plays an important role in the cell proliferation of multiple myeloma via
      the MAP kinase (ERK) pathway.
AB  - The present study was designed to explore the role of IQ motif-containing GTPase
      activating protein 1 (IQGAP1) in the cell proliferation of multiple myeloma (MM)
      via the MAP kinase (ERK) pathway. Reverse transcription-polymerase chain reaction
      (RT-PCR) and western blot analysis were carried out to evaluate the expression of
      IQGAP1 in RPMI8226, U266 and KM3 cell lines and in primary MM cells from 4 MM
      patients. shRNA-expressing plasmids were used in RPMI8226 cells to knock down
      IQGAP1 and an MTT assay was used to examine the proliferative activity of the
      RPMI8226-shIQGAP1 (clone 1), RPMI8226-shRNA negative and untransfected RPMI8226
      cells in subgroups stimulated with VEGF/IL-6 or without. Western blot analyses
      were then performed to examine the protein levels of p-ERK1/2, ERK1/2, AKT, p
      AKT, STAT3, p-STAT3 in the RPMI8226-shIQGAP1 (clone 1), RPMI8226-shRNA negative
      and untransfected RPMI8226 cells. Co-immunoprecipitation was used to verify the
      interaction between the IQGAP1 scaffold and the MAP ERK kinase. We found that
      IQGAP1 was overexpressed in the human myeloma cell lines and in the patient MM
      cells. The proliferation rate in the RPMI8226 cells was decreased when IQGAP1 was
      knocked down with shRNA. IQGAP1 was found to affect RPMI8226 cell proliferation
      by regulation of the MAP kinase (ERK1/2) pathway; IQGAP1 scaffold-MAP kinase
      (ERK) interaction was noted in the human myeloma RPMI8226 cell lines. In
      conclusion, IQGAP1 plays an important role in the cell proliferation of MM via
      the MAP kinase (ERK) pathway.

PMID- 24101134
TI  - Gene expression profile of the whole Mediator complex in human osteosarcoma and
      normal osteoblasts.
AB  - Mediator complex (MED) is an essential multi-subunit component of the
      transcription apparatus and plays a key role in the transcription regulation of
      many genes involved in several diseases, including cancer. Recently, numerous MED
      subunits have been implicated in cancer development and metastasis, and specific
      alterations in their coding genes have been found to correlate with some
      malignancies. It is conceivable that a specific MED alteration pattern can
      characterize each cancer type. However, to date, no study has reported the
      complete picture of MED subunits in a specific tumor. Thus, the aim of this study
      was to investigate for the first time the gene expression profile of the whole
      MED complex in human osteosarcoma (OS). To this purpose, we have examined all the
      MED subunit genes in three OS cell lines compared to normal osteoblasts by real
      time RT-PCR. Interestingly, our findings indicate that the expression of most of
      the MED genes is altered in OS. Moreover, a very high overexpression of MED20 and
      MED31 can be observed in all the analyzed OS cells, thus suggesting for the first
      time a potential role of these subunits in human malignancies. Overall, this
      study may open the way to other functional studies exploring the role of the
      whole complex in cancer development and progression. These findings may lead to
      the identification of novel biomarkers, which can be used also in combination
      with imaging techniques for early detection, and/or to develop novel targets for
      innovative therapeutic approaches. 

PMID- 24101136
TI  - [Reports from the Federal Conference of German Psychiatric and Psychotherapy
      Clinics].

PMID- 24101135
TI  - A comparison on expression of selected biomarkers between primary lung cancers
      and matched metastases.
AB  - Many biomarkers have been identified to be new targeted drugs for lung cancer
      treatment. Their clinical outcomes are determined by their status mainly
      evaluated from primary cancer tissues. However, metastasis is the leading cause
      of death in cancer patients. It is unclear whether their status in primary
      cancers is similar to that in corresponding metastases. Therefore, we aimed to
      evaluate similarities or differences for the selected biomarker expression
      between primary lung cancers and matched metastases and to provide evidence for
      further using these targets in metastatic tumors from lung cancer. Eleven
      patients who had received resection of paired tissues of primary lung cancers and
      matched metastases were collected. The protein expression of VEGF, HIF-1alpha,
      Met, P53, TGF-beta1, Cox-2 and TNF-alpha between paired tumors was detected by
      immunohistochemistry. The results showed that there was no statistical
      significance between primary cancers and matched metastases for the expressions
      of the selected biomarkers. The p values were more than 0.05. The major
      concordance of the selected biomarkers existed between paired primary and
      metastatic tumors. However, there were still minor differences. Differences in
      metastases compared with primary tumors were observed in respective two cases for
      VEGF, HIF-1alpha and Met, respective one case for TGF-beta1, COX2 and TNFalpha
      and three cases for P53. In conclusion, there were major concordance and minor
      difference for each biomarker between primary lung tumors and corresponding
      metastases, which may have important implications for the understanding of
      current metastasis models and treatment of advanced lung cancers.

PMID- 24101137
TI  - [Psychiatry caught between emergency response and therapy: compulsory treatment
      following the jurisprudence of the federal constitutional court and the federal
      supreme court].

PMID- 24101139
TI  - [Geriatric psychiatry as a subspecialty in the field of psychiatry and
      psychotherapy - pro].

PMID- 24101140
TI  - [Geriatric psychiatry as a subspecialty in the field of psychiatry and
      psychotherapy - contra].

PMID- 24101141
TI  - [Comment on Pfaff M, Seidl A, Angst K et al. ].

PMID- 24101143
TI  - Modulation and effects of surface groups on photoluminescence and photocatalytic
      activity of carbon dots.
AB  - To demonstrate the effects of surface atoms on photoluminescence (PL) and
      photocatalytic activities of luminescent carbon dots (CDs), we design and tailor
      the surface groups of CDs with heteroatoms by a facile and effective approach.
      The coexistence of O and N radicals in CDs results in strong PL while CDs
      containing O and Cl radicals show high photocatalytic activity. This is
      attributed to the different degrees and directions of energy band bending from
      inner to surface induced by O, N, and Cl radicals at the surface of CDs. The
      coexistence of both upward and downward band bending that are caused by the O and
      Cl radicals, respectively, in CDs is similar to an internal electronic field that
      facilitates the separation of electron-hole pairs and carrier migration, leading
      to high photocatalytic activity. These results may also be used for designing and
      tailoring optical-electronic properties of carbon nanostructures. 

PMID- 24101142
TI  - ACA12 is a deregulated isoform of plasma membrane Ca2+-ATPase of Arabidopsis
      thaliana.
AB  - Plant auto-inhibited Ca2+-ATPases (ACA) are crucial in defining the shape of
      calcium transients and therefore in eliciting plant responses to various stimuli.
      Arabidopsis thaliana genome encodes ten ACA isoforms that can be divided into
      four clusters based on gene structure and sequence homology. While isoforms from
      clusters 1, 2 and 4 have been characterized, virtually nothing is known about
      members of cluster 3 (ACA12 and ACA13). Here we show that a GFP-tagged ACA12
      localizes at the plasma membrane and that expression of ACA12 rescues the
      phenotype of partial male sterility of a null mutant of the plasma membrane
      isoform ACA9, thus providing genetic evidence that ACA12 is a functional plasma
      membrane-resident Ca2+-ATPase. By ACA12 expression in yeast and purification by
      CaM-affinity chromatography, we show that, unlike other ACAs, the activity of
      ACA12 is not stimulated by CaM. Moreover, full length ACA12 is able to rescue a
      yeast mutant deficient in calcium pumps. Analysis of single point ACA12 mutants
      suggests that ACA12 loss of auto-inhibition can be ascribed to the lack of two
      acidic residues--highly conserved in other ACA isoforms--localized at the
      cytoplasmic edge of the second and third transmembrane segments. Together, these
      results support a model in which the calcium pump activity of ACA12 is primarily
      regulated by increasing or decreasing mRNA expression and/or protein translation
      and degradation.

PMID- 24101144
TI  - Characteristics of patients admitted to the intensive care unit following self
      poisoning and their impact on resource utilisation.
AB  - BACKGROUND: Self-poisoning accounts for up to 10 % of hospital admissions, some
      of whom require admission to ICU. Few studies have looked at the epidemiology of
      these patients in an Irish setting. AIMS: To quantify the proportion of ICU
      admissions attributable to self-poisoning, to examine the characteristics and
      outcome of these patients, and to assess their ICU resource utilisation. METHODS:
      Retrospective review of ICU admissions from 2006 to 2010. Data were collected on
      patient age, sex, admission diagnosis, substances involved, APACHE II score,
      length of stay, organ support, and outcome. RESULTS: There were 80 admissions to
      ICU following self-poisoning accounting for 3.8 % of ICU admissions and 13 % of
      all hospital admissions for self-poisoning. M:F ratio was 0.9:1. Mean age 35
      (range 16-75), APACHE II score 14 (2-36). Commonest substances involved were
      benzodiazepines, opioids, tricycle antidepressants. Median ICU stay was 2 days
      (IQR 0.96-4.5). 84 % of patients were ventilated, 27.5 % required inotropic
      support, 14 % renal replacement therapy. When opioids were involved requirement
      for inotropes and CRRT were higher. ICU mortality was 6.3 %. These patients
      consumed 280 bed days. CONCLUSION: Self-poisoning accounted for 3.8 % of ICU
      admissions. Patients tend to require a short period of ventilation, with a
      minority requiring additional organ support. The cost of ICU care is calculated
      based on previously published methodology to be <euro>7,717 per patient.
      Extrapolated nationally the annual cost for ICU care for self-poisoning is
      estimated to be in the order of <euro>5 m.

PMID- 24101145
TI  - Transient severe hyperbilirubinemia after hepatic arterial infusion of
      oxaliplatin in patients with liver metastases.
AB  - PURPOSE: We have observed severe, but rapidly reversible, hyperbilirubinemia in
      patients receiving hepatic arterial infusion (HAI) of oxaliplatin. We performed a
      retrospective analysis to characterize this unusual phenomenon. METHODS: We
      reviewed the electronic medical records of 113 consecutive patients receiving HAI
      oxaliplatin to describe the associated hyperbilirubinemia. RESULTS: Four of 113
      patients (3.5 %) presented with transient, severe (grade 3/4) hyperbilirubinemia
      post-HAI oxaliplatin. Peak levels of total bilirubin within 10-16 h of starting
      HAI oxaliplatin were 4.6, 12.2, 12.8, and 21.2 mg/dL and declined rapidly (within
      24 after stopping treatment). One out of four patients experienced severe
      abdominal pain, and another patient had an infusion reaction (hypertension and
      hypoxemia) that reversed after discontinuation of infusion. Total bilirubin was
      predominantly direct. No significant decline in hemoglobin or increase in
      alkaline phosphatase occurred. Increase in liver transaminases post-infusion was
      mild to moderate (grades 1-3) and was seen after HAI oxaliplatin regardless of
      the emerged hyperbilirubinemia. CONCLUSIONS: Severe hyperbilirubinemia is a rare
      but rapidly reversible adverse effect of HAI oxaliplatin and may be accompanied
      by an abdominal pain syndrome or infusion reaction. Treating physicians should be
      aware for the potential of this reaction. The mechanism of this unusual reaction
      merits further investigation.

PMID- 24101146
TI  - Preclinical pharmacokinetic/pharmacodynamic/efficacy relationships for alisertib,
      an investigational small-molecule inhibitor of Aurora A kinase.
AB  - PURPOSE: Alisertib (MLN8237) is an investigational inhibitor of Aurora A kinase
      (AAK). Aurora A plays an essential role in the regulation of spindle assembly and
      chromosome alignment during mitosis. Inhibition of Aurora A by alisertib in
      tissue culture has previously been demonstrated to lead to improper chromosomal
      alignment and disruption of spindle organization, resulting in a transient
      mitotic delay. The spindle organization defects induced by alisertib have been
      used to develop a pharmacodynamic (PD) assay for Aurora A inhibition based on the
      percentage of mitotic cells with proper chromosomal alignment at the metaphase
      plate (% aligned spindles, abbreviated as AS). The transient mitotic delay that
      occurs with AAK inhibition permits the use of the mitotic index (the fraction of
      cells in the population currently undergoing mitosis, abbreviated as MI) as an
      additional PD assay. When the two PD assays were used in Phase I clinical trials,
      the reduction in AS was strongly correlated with dose levels and exposures in
      patients from single time point PD measurements; however, MI failed to show any
      correlation. To further understand this clinical finding, we constructed
      PK/PD/efficacy models for AS and MI that can precisely capture the temporal
      dynamics of the PD markers from in vivo xenograft studies. METHODS: A PK/PD study
      was conducted using a single oral dose of alisertib at 3, 10, and 20 mg/kg in HCT
      116 xenografts implanted subcutaneously in mice. An extravascular, two
      compartmental pharmacokinetic (PK) model was used to describe the drug kinetics.
      Consistent with the mechanistic hypothesis for AAK inhibition, the PD biomarkers
      such as AS and MI were fitted to PK using a direct response inhibitory sigmoid
      model and an indirect response turnover model, respectively. The antitumor
      activity of alisertib dosed orally for 21 days with different dose levels and
      schedules was evaluated. RESULTS: The PK/PD models showed a fast, sustained
      response for AS after alisertib administration, whereas MI exhibited a slow,
      transient response. The PK/efficacy relationship for alisertib in HCT-116
      xenografts closely corresponds to the PK/PD relationship for the PD markers, with
      all three IC50s in close agreement (303, 270, and 280 nM, respectively).
      CONCLUSION: The PK/PD and PK/efficacy models show that both AS and MI are equally
      relevant as mechanism-based PD markers to capture drug activity. However, of the
      two PD markers, the fast, sustained response of AS makes it the only clinically
      viable PD marker for defining a dose-response relationship, as its maximal effect
      can be captured from a wider time window with a single PD sampling; while the
      window to capture dose-related MI response is narrower.

PMID- 24101147
TI  - (13)C-uracil breath test to predict 5-fluorouracil toxicity in gastrointestinal
      cancer patients.
AB  - PURPOSE: Up to 30 % of patients undergoing 5-fluorouracil (5FU)-based
      chemotherapy experience severe toxicity. Dihydropyrimidine dehydrogenase (DPD)
      deficiency explains 36-61 % of cases. Predicting toxicity is an unmet challenge.
      Uracil breath test (UraBT) consists of measuring (13)CO2 in exhaled breath after
      ingestion of 2-(13)C-uracil to evaluate pyrimidine (and 5FU) catabolism. METHODS:
      We studied 33 gastrointestinal cancer patients previously exposed to 5FU:
      Thirteen had grade 3-4 and 20, grade 0-1 toxicity. The following tests were used
      to evaluate pyrimidine catabolism: (1) sequencing of three exons of DPYD; (2)
      plasma dihydrouracil/uracil ratio (UH2/U); and (3) UraBT. We tested the
      performance of UraBT to discriminate patients who had grade 0-1 toxicity versus
      grade 3-4 toxicity and patients with and without proven DPD deficiency. RESULTS:
      Of the thirteen patients, four grade 3-4 toxicity patients were proved to be DPD
      deficient: Three had deleterious mutations (IVS14 + 1G>A in one; single
      nucleotide polymorphism 2846A>T in two), and one had low UH2/U ratio. Mean delta
      over baseline in 50 min (DOB50) significantly differed between groups.
      DOB50<=161.4 discriminated individuals with grade 3-4 versus grade 0-1 toxicity
      (sensitivity = 61.5 %; specificity = 85 %) and DPD-deficient versus non-DPD
      deficient (sensitivity = 75 %; specificity = 85 %). CONCLUSION: UraBT has
      moderate accuracy in discriminating individuals who manifested severe toxicity
      from those who had mild or no toxicity to 5FU.

PMID- 24101149
TI  - Discontinuing anticoagulation following successful atrial fibrillation ablation
      in patients with prior strokes.
AB  - PURPOSE: This study was conducted to examine the outcomes in patients with prior
      stroke/transient ischemic attack (CVA/TIA) after atrial fibrillation (AF)
      ablation and the feasibility of discontinuing oral anticoagulation (OAC).
      METHODS: This study examined long-term outcomes following AF ablations in 108
      patients with a history of prior thromboembolic CVA/TIA. Because of risks of OAC,
      we frequently discontinue OAC in these patients after successful ablation. These
      patients understand the risks/benefits of discontinuing OAC and remain on OAC for
      a longer time following successful AF ablation, compared to our patients without
      prior CVA/TIA. RESULTS: Patient age was 66.2 +/- 9.0 years with an average CHADS2
      score = 3.0 +/- 0.9 and CHA2DS2-VASc score = 4.1 +/- 1.4. Following 1.24
      ablations, 71 (65.7%) patients were AF free 2.8 +/- 1.6 (median 2.3) years after
      their last ablation. OAC was discontinued in 55/71 (77.5%) patients an average of
      7.3 months following the final ablation. These 55 patients had 2.2 +/- 1.3
      (median 1.8) years of follow-up off of OAC. Kaplan-Meier analysis suggests little
      AF recurrence >1 year following initial or final ablations, suggesting that 1
      year post successful ablation may be the appropriate time to consider
      discontinuing OAC. Thirty-seven patients had AF postablation, and 32/37 (86.5%)
      remained on OAC. One patient with a mechanical valve had a stroke despite OAC.
      Bleeding occurred in 8.3% of patients on OAC and 0% of patients off OAC (P =
      0.027). CONCLUSIONS: Patients with prior CVA/TIAs, who undergo successful AF
      ablation, have a low incidence of subsequent thromboembolic events. Most patients
      who appear AF free postablation may be able to discontinue OAC after successful
      ablation with a low thromboembolic risk and with a reduced bleeding risk.

PMID- 24101150
TI  - Determinants of immediate success for catheter ablation of atrioventricular nodal
      reentry tachycardia in patients without junctional rhythm.
AB  - BACKGROUND AND PURPOSE: To investigate the independent predictors of immediate
      success for atrioventricular nodal reentry tachycardia (AVNRT) catheter ablation
      in patients without accelerated junctional rhythm (JR). METHODS: The study
      included 172 consecutive patients with AVNRT undergoing slow pathway ablation
      that had no JR during the radiofrequency pulses. The diagnosis of AVNRT was made
      using the classic criteria of documenting antegrade atrio-His or retrograde
      ventriculoatrial (VA) jump and arrhythmia induction. Successful ablation was
      defined as the inability to induce tachycardia with and without the infusion of
      isoproterenol and the absence of more than one AV-nodal echo. RESULTS: The
      clinical independent predictors of successful ablation in the studied patients
      were identified as age >= 60, ablation-site location (mid-septal rather than
      posteroseptal), and baseline heart rate >= 100 beat per minute. The predictive
      performance of the risk model was very good and the calibration of the risk model
      was acceptable. CONCLUSIONS: Our study suggests predictive factors that can be
      used to gauge procedural success in AVNRT patients without accelerated JR during
      ablation.

PMID- 24101151
TI  - Resilience in patients after allogeneic stem cell transplantation.
AB  - PURPOSE: After undergoing allogeneic stem cell transplantation (alloSCT),
      patients adapt in very different ways to their taxing situation. Some patients
      cope very well; others almost seem to fail. Psychosocial variables are important
      factors for successful reintegration. Besides quality of life, resilience may
      help to understand the variance in individual differences in adaptation after
      alloSCT. METHODS: A pilot study at the University Hospital Muenster, Germany,
      assessed resilience in patients after alloSCT. The sample included 75 patients
      (leukemia, lymphoma, myeloma, aplastic anemia) aged 20-76 years. The instruments
      Resilience Scale RS-25, Hospital Anxiety and Depression Scale, General Self
      efficacy Scale, and EORTC QLQ-C30 were used. RESULTS: Resilience is positively
      correlated with quality of life (Spearman's rho 0.587) and social functioning
      (0.472), negatively with anxiety (-0.491) and depression (-0.577). Dividing the
      sample at the median resilience score of 144 reveals that high-resilience
      patients report less anxiety (p = 0.008) and depression (p < 0.001); higher
      physical (p = 0.041), emotional (p = 0.030), and social functioning (p = 0.003);
      and a better quality of life (p < 0.001) than low-resilience patients. No effects
      on resilience were found for age, gender, and primary disease entity. The high
      correlation of resilience and self-efficacy (r = 0.698) shows the strong
      relationship between the two concepts. Our results indicate a potential influence
      of the time span from alloSCT on patients' resilience. CONCLUSIONS: Resilience
      should be considered as a protective psychosocial factor for patients after
      alloSCT. A high degree of resilience can help patients to adapt to their
      situation and to resume their everyday life.

PMID- 24101152
TI  - Parental depressive symptoms and childhood cancer: the importance of financial
      difficulties.
AB  - PURPOSE: Research suggests a relationship between caring for a child with cancer
      and psychological distress in caregivers. Less evident is the role which
      financial difficulties might play in this relationship. We sought to determine if
      caring for a child with cancer was related to clinically relevant depressive
      symptoms among parents, whether or not financial difficulties mediated this
      relationship, and if financial difficulties were independently associated with
      symptoms of depression among parents of children with cancer. METHODS: Data are
      from 215 parents of children diagnosed with cancer or brain tumors (n = 75) and a
      comparison group of parents of healthy children (n = 140). Multiple logistic
      regression analyses were used to assess the factors associated with reporting
      clinically relevant depressive symptoms. RESULTS: Caring for a child with cancer
      was associated with increased odds of clinically relevant depressive symptoms in
      parents (OR = 4.93; 95 % CI 1.97-12.30), controlling for covariates. The
      mediating effect of financial burden on this relationship was not statistically
      significant. However, among parents of children with cancer, negative financial
      life events increased the likelihood of reporting symptoms of depression (OR =
      4.89; 95 % CI 1.26-18.96). CONCLUSIONS: Caring for a child with cancer was
      associated with depressive symptoms for parents. Financial difficulties were the
      strongest correlate of these symptoms among parents of children with cancer. Our
      results suggest that it may not only be the burden of caring for the child with
      cancer but also the associated financial difficulties that contribute to a higher
      likelihood of depressive symptoms in parents.

PMID- 24101153
TI  - Generation of prostate tumor-initiating cells is associated with elevation of
      reactive oxygen species and IL-6/STAT3 signaling.
AB  - How prostate cancer is initiated remains a topic of debate. In an effort to
      establish a human model of prostate carcinogenesis, we adapted premalignant human
      prostate EPT2-D5 cells to protein-free medium to generate numerous tight prostate
      spheres (D5HS) in monolayer culture. In contrast to EPT2-D5 cells, the newly
      generated D5HS efficiently formed large subcutaneous tumors and subsequent
      metastases in vivo, showing the tumorigenicity of D5HS spheres. A striking
      production of interleukin (IL)-6 mRNA and protein was found in D5HS cells. The
      essential roles of IL-6 and the downstream STAT3 signaling in D5HS tumor sphere
      formation were confirmed by neutralizing antibody, chemical inhibitors, and
      fluorescent pathway reporter. In addition, elevated reactive oxygen species (ROS)
      produced upon protein depletion was required for the activation of IL-6/STAT3 in
      D5HS. Importantly, a positive feedback loop was found between ROS and IL-6 during
      tumor sphere formation. The association of ROS/IL-6/STAT3 to the carcinogenesis
      of human prostate cells was further examined in xenograft tumors and verified by
      limiting dilution implantations. Collectively, we have for the first time
      established human prostate tumor-initiating cells based on physiologic adaption.
      The intrinsic association of ROS and IL-6/STAT3 signaling in human prostate
      carcinogenesis shed new light on this relationship and define therapeutic targets
      in this setting.

PMID- 24101154
TI  - CDK1 phosphorylation of YAP promotes mitotic defects and cell motility and is
      essential for neoplastic transformation.
AB  - The Yes-associated protein, YAP, is a downstream effector of the Hippo pathway of
      cell-cycle control that plays important roles in tumorigenesis. Hippo-mediated
      phosphorylation YAP, mainly at S127, inactivates YAP function. In this study, we
      define a mechanism for positive regulation of YAP activity that is critical for
      its oncogenic function. Specifically, we found that YAP is phosphorylated in
      vitro and in vivo by the cell-cycle kinase CDK1 at T119, S289, and S367 during
      the G2-M phase of the cell cycle. We also found that ectopic expression of a
      phosphomimetic YAP mutant (YAP3D, harboring T119D/S289D/S367D) was sufficient to
      induce mitotic defects in immortalized epithelial cells, including centrosome
      amplification, multipolar spindles, and chromosome missegregation. Finally, we
      documented that mitotic phosphorylation of YAP was sufficient to promote cell
      migration and invasion in a manner essential for neoplastic cell transformation.
      In support of our findings, CDK1 inhibitors largely suppressed cell motility
      mediated by activated YAP-S127A but not the phosphomimetic mutant YAP3D.
      Collectively, our results reveal a previously unrecognized mechanism for
      controlling the activity of YAP that is crucial for its oncogenic function
      mediated by mitotic dysregulation.

PMID- 24101155
TI  - Factors predicting peritoneal recurrence in advanced gastric cancer: implication
      for adjuvant intraperitoneal chemotherapy.
AB  - BACKGROUND: Despite adjuvant chemotherapy, patients with advanced gastric cancer
      (AGC) often develop recurrence, and the peritoneum is the most common site of
      recurrence. Therefore, intraperitoneal chemotherapy (IPC) has been proposed as a
      treatment option. The aim of this study was to select the eligible patients for
      application of IPC. METHODS: A total of 805 patients with AGC who underwent
      curative D2 gastrectomy between May 2003 and December 2009 were included in this
      study. Risk factors for peritoneal recurrence were analyzed. RESULTS: Recurrence
      developed in 245 patients (30.4 %). The first site of recurrence was the
      peritoneum in 144 patients (58.8 %), and the 5-year peritoneal recurrence-free
      survival was 79.3 %. Depth of tumor invasion >=T3, extensive lymph node
      metastasis (N3), Bormann type 4, infiltrative type (Ming's classification), and
      venous invasion were independent risk factors for peritoneal recurrence. In
      subgroup analysis with patients who had received adjuvant chemotherapy (n = 481),
      depth of tumor invasion >=T3, Bormann type 4, infiltrative type (Ming's
      classification), and venous invasion were independent risk factors for peritoneal
      recurrence. When a peritoneal recurrence risk index was made with each risk
      factor assigned 1 point (2 points for T4 stage), peritoneal recurrence rates with
      0, 1, 2, 3, 4, or 5 points were 0 %, 3.9 %, 13.1 %, 33.3 %, 44.0 %, and 72.0 %,
      respectively, in those patients. CONCLUSIONS: Patients at higher risk for
      peritoneal recurrence can be identified from the findings of this study. Further
      prospective studies are required to evaluate the usefulness of IPC for these
      patients.

PMID- 24101156
TI  - Critical role of nitric oxide in the modulation of prepulse inhibition in Swiss
      mice.
AB  - RATIONALE: Nitric oxide (NO) modulates the dopamine uptake and release processes
      and appears to be implicated in dopamine-related pathologies, such as
      schizophrenia. However, it is unclear whether there is excess or deficient NO
      synthesis in schizophrenia pathophysiology. Analyses of the intracellular
      pathways downstream of NO system activation have identified the cyclic nucleotide
      cyclic guanosine monophosphate (cGMP) as a possible target for drug development.
      Defects in the sensorimotor gating of the neural mechanism underlying the
      integration and processing of sensory information have been detected across
      species through prepulse inhibition (PPI). OBJECTIVES: The aim of this study was
      to investigate the effects of NO/cGMP increase on sensorimotor gating modulation
      during dopamine hyperfunction. METHODS: Mice were treated with NO donors and
      subjected to the PPI test. Treatment with the NO donor sodium nitroprusside was
      preceded by pretreatment with a soluble guanylate cyclase (sGC) inhibitor.
      Additionally, the mice were treated with NO donors and phosphodiesterases
      inhibitors prior to amphetamine treatment. RESULTS: Pretreatment with the NO
      donors enhanced the PPI response and attenuated the amphetamine-disruptive
      effects on the PPI. The sGC inhibitor did not modify the sodium nitroprusside
      effects. Additionally, the cGMP increase induced by a specific phosphodiesterase
      inhibitor did not modify the amphetamine-disruptive effect. CONCLUSIONS: This
      study provides the first demonstration that an increase in NO can improve the PPI
      response and block the amphetamine-disruptive effects on the PPI response. Our
      data are consistent with recent clinical results. However, these effects do not
      appear to be related to an increase in cGMP levels, and further investigation is
      thus required.

PMID- 24101159
TI  - Occupational engagement among community dwelling older people: A time-geographic
      perspective?.
AB  - How older people spend their time in different occupations could contribute to
      our understanding of everyday life in healthy ageing. This study adopted a time
      geographic method and occupational perspective to explore the occupational
      engagement of community dwelling older people. The term occupational engagement
      encompasses what people do, where and with whom they spend their time and the
      perceived level of competence and meaningfulness of their time use. Nineteen
      volunteers born between 1932 and 1933, living alone in an urban area in northern
      Sweden and receiving no home care services, completed open time-geographic
      diaries for 5 days in May 2010. The diary data were analyzed using Daily Life
      software program. The study revealed the complexity and the diversity of the
      older people's occupational engagement and that most of their time was spent
      alone in their home. The older people reported they were very good at doing
      almost half of the occupations in which they engaged and that their occupations
      were primarily either very meaningful or meaningful. While some methodological
      limitations were identified, time-geographic studies of community dwelling older
      people living independently are considered to have potential to contribute to
      community and social planning for older people as they can provide interesting
      insights to older persons' time use and occupational needs. 

PMID- 24101157
TI  - Synergistic interaction between caloric restriction and amphetamine in food
      unrelated approach behavior of rats.
AB  - RATIONALE: Approach behavior is regulated by the brain integrating information
      about environment and body state. Psychoactive drugs interact with this process.
      OBJECTIVES: We examined the extent to which caloric (i.e., food) restriction,
      amphetamine (AMPH) and lithium interact in potentiating locomotor activity and
      responding reinforced by visual stimulus (VS), a reward unrelated to energy
      homeostasis. METHODS: Rats either had ad libitum access to food or received daily
      rations that maintained 85-90 % of their original body weights. Leverpressing
      turned on a cue light for 1 s and turned off house light for 5 s. AMPH and
      lithium were administered through intraperitoneal injections and diet,
      respectively. RESULTS: Food restriction or AMPH (1 mg/kg) alone had little effect
      on VS-reinforced responding; however, the combination of the two conditions
      markedly potentiated VS-reinforced responding (fourfold). Food restriction
      lasting 7 days or longer was needed to augment AMPH's effect on VS-reinforced
      responding. AMPH (0.3-3 mg/kg) potentiated locomotor activity similarly between
      food-restricted and ad libitum groups. Repeated injections of AMPH-sensitized
      locomotor activity, but not VS-reinforced responding. In addition, while chronic
      lithium treatments (0.2 % lithium carbonate chow) reduced VS-reinforced
      responding, chronic lithium further augmented AMPH-potentiated VS-reinforced
      responding. CONCLUSIONS: Food restriction interacts with psychoactive drugs to
      potentiate goal-directed responding unrelated to food seeking in a much more
      powerful manner than previously thought. The novel finding that lithium can
      augment a psychostimulant effect of AMPH suggests caution when combining lithium
      and psychostimulant drugs in clinical settings.

PMID- 24101158
TI  - The impact of sustained and intermittent docetaxel chemotherapy regimens on
      cognition and neural morphology in healthy mice.
AB  - RATIONALE: A subset of cancer survivors demonstrates impairments in cognition
      long after chemotherapy completion. At present, it is unclear whether these
      changes are due to direct neurotoxic effects of chemotherapy. OBJECTIVES: This
      study examined the impact of variable docetaxel (DTX) chemotherapy dosing on
      brain DTX exposure via analyses of neural morphology and changes in cognition.
      METHODS: Male CD-1 mice were treated with DTX either intermittently (8 mg/kg i.p.
      weekly) or via a sustained delivery system (DTX-PoLigel), which continuously
      releases DTX. Both groups received total DTX doses of 32 mg/kg. Mice were
      assessed on the novel object recognition (NOR) task and the Morris water maze
      (MWM) shortly after treatment. RESULTS: Post-treatment behavioral testing
      demonstrated impaired NOR in mice treated with either dosing schedule relative to
      controls. No differences were observed between groups in MWM training and initial
      testing, though control mice performed better than chance while DTX-treated mice
      did not. Appreciable amounts of DTX were found in the brain after both treatment
      regimens. DTX treatment did not significantly increase levels of apoptosis within
      the CNS. However, some elevation in neural autophagy was observed following DTX
      treatment. Analysis of astrocytic activation demonstrated that intermittent DTX
      treatment resulted in an elevation of GFAP-positive astrocytes for 48 h after
      administration. Sustained chemotherapy demonstrated prolonged but lower levels of
      astrocyte activation over 9 days following implantation. CONCLUSIONS: DTX
      treatment induced cognitive impairment shortly after treatment. Further, these
      findings suggest an association between DTX dosing, neurotoxicity, and cognitive
      effects.

PMID- 24101160
TI  - Motivational interviewing in a web-based physical activity intervention:
      questions and reflections.
AB  - The purpose of this study was to identify which question/reflection format leads
      to the most favorable results in terms of effect on autonomous motivation and
      appreciation for the intervention in a web-based computer-tailored physical
      activity (PA) intervention, based on principles from self-determination theory
      (SDT) and motivational interviewing (MI). For this purpose, a randomized trial
      was conducted among 465 Dutch adults, comparing three web-based computer-tailored
      MI/SDT PA interventions, including (i) exclusively open-ended questions (without
      skillful reflections), (ii) exclusively multiple choice questions (with skillful
      reflections) and (iii) including both question types (with skillful reflections).
      Measurements included motivation-related determinants of PA and process
      variables, measured at baseline, directly following the intervention and 1-month
      post-intervention. Results suggest that open-ended questions represent an
      important element in web-based MI in terms of effect on autonomous motivation. In
      order to optimize appreciation of the intervention, a combination of both open
      ended and multiple choice question types seems to hold most promise. The findings
      of this study suggest that both open-ended and multiple choice questions should
      be included in web-based computer-tailored SDT/MI PA interventions. More research
      is needed to reveal the optimal configuration of this novel intervention type. 

PMID- 24101161
TI  - Simvastatin reduces melanoma progression in a murine model.
AB  - Statins are a class of drugs that inhibit the rate-limiting step in the
      cholesterol biosynthetic pathway and show an anticancer effect, probably through
      the inhibition of cell proliferation. To date, the exact mechanism of cancer cell
      growth arrest induced by statins is not known. We report that simvastatin is able
      to induce apoptosis in melanoma cells but not in normal cells and also able to
      contrast the growth of tumor in an experimental melanoma murine model. We
      observed a delay in the tumor development in almost the 50% of the simvastatin
      administered animals and a strong reduction of the tumor volume with a
      differences of ~150% compared to the controls. Also the survival rate was
      significantly higher in mice that received the drug with a survival increase of
      ~130% compared to the controls. The tumor growth reduction in mice was supported
      by the results of cell migration assay, confirming that simvastatin clearly
      reduced cell migration. Moreover, simvastatin induced a strong downregulation of
      NonO gene expression, an important growth factor involved in the splicing
      regulation. This result could explain the decrease of melanoma cells
      proliferation, suggesting a possible action mechanism. The results derived from
      our experiments may sustain the many reports on the anticancer inhibitory
      property of statins and encourage new studies on this drug for a possible use in
      therapy, probably in combination with conventional chemotherapy. 

PMID- 24101162
TI  - Obstructive sleep apnea: incidence and impact on hypertension?
AB  - There are a number of recent studies evaluating sleep disordered breathing and
      its treatment in the context of blood pressure control. In addition, total sleep
      time and subjective sleep complaints may also be related to hypertension; these
      will be reviewed. Recent findings in original articles document that sleep
      disordered breathing and decreased total sleep time, if chronic, may contribute
      to an increased risk for development of hypertension. Treatment of sleep apnea
      with either continuous positive airway pressure (CPAP) or oral devices are
      reasonable treatment approaches for obstructive sleep apnea (OSA), but the data
      on the effect on blood pressure remain unclear. In summary, treatment of sleep
      disordered breathing may help reduce blood pressure or decrease development of
      incident hypertension. 

PMID- 24101163
TI  - Common conditions in pediatric surgery.
AB  - Primary care physicians are generally the first contacts of the parents of
      children with any disease. Management protocols and methods of the surgical
      conditions in children have undergone changes over time and the aim of this
      review is to update the knowledge base of clinicians. New technologies like
      laparoscopy and endoscopic surgery are available for management. The optimal
      treatment of any surgical condition requires that appropriate procedure is
      performed at the optimal time by a pediatric surgeon who is best trained for
      management of these conditions. 

PMID- 24101164
TI  - Lack of thelarche as the presenting feature of bilateral congenital amastia.

PMID- 24101165
TI  - Identification of novel mutation in autosomal recessive infantile malignant
      osteopetrosis.

PMID- 24101166
TI  - Old age mortality and macroeconomic cycles.
AB  - BACKGROUND: As mortality is more and more concentrated at old age, it becomes
      critical to identify the determinants of old age mortality. It has counter
      intuitively been found that mortality rates at all ages are higher during short
      term increases in economic growth. Work-stress is found to be a contributing
      factor to this association, but cannot explain the association for the older,
      retired population. METHODS: Historical figures of gross domestic product (Angus
      Maddison) were compared with mortality rates (Human Mortality Database) of middle
      aged (40-44 years) and older people (70-74 years) in 19 developed countries for
      the period 1950-2008. Regressions were performed on the de-trended data,
      accounting for autocorrelation and aggregated using random effects models.
      RESULTS: Most countries show pro-cyclical associations between the economy and
      mortality, especially with regard to male mortality rates. On average, for every
      1% increase in gross domestic product, mortality increases with 0.36% for 70-year
      old to 74-year-old men (p<0.001) and 0.38% for 40-year-old to 44-year-old men
      (p<0.001). The effect for women is 0.18% for 70-year-olds to 74-year-olds
      (p=0.012) and 0.15% for 40-year-olds to 44-year-olds (p=0.118). CONCLUSIONS: In
      developed countries, mortality rates increase during upward cycles in the
      economy, and decrease during downward cycles. This effect is similar for the
      older and middle-aged population. Traditional explanations as work-stress and
      traffic accidents cannot explain our findings. Lower levels of social support and
      informal care by the working population during good economic times can play an
      important role, but this remains to be formally investigated.

PMID- 24101167
TI  - Socioeconomic and behavioural risk factors for adverse winter health and social
      outcomes in economically developed countries: a systematic review of quantitative
      observational studies.
AB  - BACKGROUND: Mortality and morbidity rates are often highest during the winter
      period, particularly in countries with milder climates. A growing body of
      research has identified potential socioeconomic, housing and behavioural
      mediators of cold weather-related adverse health and social outcomes, but an
      inclusive systematic review of this literature has yet to be performed. METHODS:
      A systematic review, with narrative synthesis, of observational research
      published in English between 2001 and 2011, which quantified associations between
      socioeconomic, housing or behavioural factors and cold weather-related adverse
      health or social outcomes. RESULTS: Thirty-three studies met the inclusion
      criteria. Average study quality was not high. Most studies failed to control for
      all relevant confounding factors, or to conduct research over a long enough
      period to ascertain causality. Low income, housing conditions and composite fuel
      poverty measures were most consistently associated with cold weather-related
      adverse health or social outcomes. CONCLUSIONS: This review identified
      socioeconomic, housing and behavioural factors associated with a range of cold
      weather-related adverse health or social outcomes. Only tentative conclusions can
      be drawn due to the limitations of existing research. More robust studies are
      needed to address the methodological issues identified and uncover causal
      associations. A review of qualitative and intervention studies would help to
      inform policies to reduce the adverse health and social impacts of cold weather.

PMID- 24101168
TI  - A systematic review of air pollution and incidence of out-of-hospital cardiac
      arrest.
AB  - INTRODUCTION: Studies have linked air pollution with the incidence of acute
      coronary artery events and cardiovascular mortality but the association with out
      of-hospital cardiac arrest (OHCA) is less clear. AIM: To examine the association
      of air pollution with the occurrence of OHCA. METHODS: Electronic bibliographic
      databases (until February 2013) were searched. Search terms included common air
      pollutants and OHCA. Studies of patients with implantable cardioverter
      defibrillators and OHCA not attended by paramedics were excluded. Two independent
      reviewers (THKT and TAW) identified potential studies. Methodological quality was
      assessed by the Newcastle-Ottawa Scale. RESULTS: Of 849 studies, 8 met the
      selection criteria. Significant associations between particulate matter (PM)
      exposure (especially PM(2.5)) and OHCA were found in 5 studies. An increase of
      OHCA risk ranged from 2.4% to 7% per interquartile increase in average PM
      exposure on the same day and up to 4 days prior to the event. A large study found
      ozone increased the risk of OHCA within 3 h prior to the event. The strongest
      risk OR of 3.8-4.6% per 20 parts per billion ozone increase of the average level
      was within 2 h prior to the event. Similarly, another study found an increased
      risk of 18% within 2 days prior to the event. CONCLUSIONS: Larger studies have
      suggested an increased risk of OHCA with air pollution exposure from PM(2.5) and
      ozone.

PMID- 24101169
TI  - Sentinel lymph node surgery after neoadjuvant chemotherapy in patients with node
      positive breast cancer: the ACOSOG Z1071 (Alliance) clinical trial.
AB  - IMPORTANCE: Sentinel lymph node (SLN) surgery provides reliable nodal staging
      information with less morbidity than axillary lymph node dissection (ALND) for
      patients with clinically node-negative (cN0) breast cancer. The application of
      SLN surgery for staging the axilla following chemotherapy for women who initially
      had node-positive cN1 breast cancer is unclear because of high false-negative
      results reported in previous studies. OBJECTIVE: To determine the false-negative
      rate (FNR) for SLN surgery following chemotherapy in women initially presenting
      with biopsy-proven cN1 breast cancer. DESIGN, SETTING, AND PATIENTS: The American
      College of Surgeons Oncology Group (ACOSOG) Z1071 trial enrolled women from 136
      institutions from July 2009 to June 2011 who had clinical T0 through T4, N1
      through N2, M0 breast cancer and received neoadjuvant chemotherapy. Following
      chemotherapy, patients underwent both SLN surgery and ALND. Sentinel lymph node
      surgery using both blue dye (isosulfan blue or methylene blue) and a radiolabeled
      colloid mapping agent was encouraged. MAIN OUTCOMES AND MEASURES: The primary end
      point was the FNR of SLN surgery after chemotherapy in women who presented with
      cN1 disease. We evaluated the likelihood that the FNR in patients with 2 or more
      SLNs examined was greater than 10%, the rate expected for women undergoing SLN
      surgery who present with cN0 disease. RESULTS: Seven hundred fifty-six women were
      enrolled in the study. Of 663 evaluable patients with cN1 disease, 649 underwent
      chemotherapy followed by both SLN surgery and ALND. An SLN could not be
      identified in 46 patients (7.1%). Only 1 SLN was excised in 78 patients (12.0%).
      Of the remaining 525 patients with 2 or more SLNs removed, no cancer was
      identified in the axillary lymph nodes of 215 patients, yielding a pathological
      complete nodal response of 41.0% (95% CI, 36.7%-45.3%). In 39 patients, cancer
      was not identified in the SLNs but was found in lymph nodes obtained with ALND,
      resulting in an FNR of 12.6% (90% Bayesian credible interval, 9.85%-16.05%).
      CONCLUSIONS AND RELEVANCE: Among women with cN1 breast cancer receiving
      neoadjuvant chemotherapy who had 2 or more SLNs examined, the FNR was not found
      to be 10% or less. Given this FNR threshold, changes in approach and patient
      selection that result in greater sensitivity would be necessary to support the
      use of SLN surgery as an alternative to ALND. TRIAL REGISTRATION:
      clinicaltrials.gov Identifier: NCT00881361.

PMID- 24101170
TI  - Insights into the interactions of cyanobacteria with uranium.
AB  - Due to various activities associated with nuclear industry, uranium is migrated
      to aquatic environments like groundwater, ponds or oceans. Uranium forms stable
      carbonate complexes in the oxic waters of pH 7-10 which results in a high degree
      of uranium mobility. Microorganisms employ various mechanisms which significantly
      influence the mobility and the speciation of uranium in aquatic environments.
      Uranyl bioremediation studies, this far, have generally focussed on low pH
      conditions and related to adsorption of positively charged UO2 (2+) onto
      negatively charged microbial surfaces. Sequestration of anionic uranium species,
      i.e. [UO2(CO3) 2 (2-) ] and [UO2(CO3) 3 (4-) ] onto microbial surfaces has
      received only scant attention. Marine cyanobacteria are effective metal
      adsorbents and represent an important sink for metals in aquatic environment.
      This article addresses the cyanobacterial interactions with toxic metals in
      general while stressing on uranium. It focusses on the possible mechanisms
      employed by cyanobacteria to sequester uranium from aqueous solutions above
      circumneutral pH where negatively charged uranyl carbonate complexes dominate
      aqueous uranium speciation. The mechanisms demonstrated by cyanobacteria are
      important components of biogeochemical cycle of uranium and are useful for the
      development of appropriate strategies, either to recover or remediate uranium
      from the aquatic environments. 

PMID- 24101171
TI  - PML overexpression inhibits proliferation and promotes the osteogenic
      differentiation of human mesenchymal stem cells.
AB  - The promyelocytic leukemia (PML) gene, as an important tumor-suppressor, has been
      proven to regulate stem cell function in multiple tissues; however its role in
      human mesenchymal stem cells (hMSCs) remains unclear. In the present study, the
      effect of PML on regulating the proliferation and osteogenic differentiation of
      hMSCs was explored. New downstream genes that may be responsible for the
      regulation of PML were found, and possible mechanisms were analyzed. The
      lentiviral vector which encodes full-length human PML cDNA or shRNA against PML
      was transfected into hMSCs. RT-PCR and western blotting were used to detect mRNA
      and protein expression. Flow cytometry was used to analyze apoptosis and the cell
      cycle distribution. Osteogenic differentiation of hMSCs was induced by osteo
      inductive medium for 7 to 14 days. cDNA microarray was used to scan the gene
      expression profile and to identify significant changes in gene expression. In the
      present study, we found that PML was stably expressed in hMSCs, and the
      expression was increased time-dependently along with cell osteogenic
      differentiation. Overexpression of PML inhibited hMSC proliferation by inducing
      apoptosis and arresting the cell cycle. However, PML enhanced the osteoblast
      differentiation potential of hMSCs. PML-overexpressing hMSCs had a significant
      increase in mineralized matrix production and ALP activity on day 7 under
      osteogenic or non-osteogenic differentiation conditions. Upregulation of integrin
      binding sialoprotein (IBSP, bone sialoprotein) induced by PML overexpression was
      found. Our data indicate that PML regulates hMSCs as an inhibitor of cell
      proliferation but a promoter of osteogenic differentiation.

PMID- 24101172
TI  - Expression of estrogen receptor alpha and beta in esophageal squamous cell
      carcinoma.
AB  - Estrogen receptors (ERs) are frequently expressed in human tumor tissues. There
      have been several studies concerning ER expression in esophageal cancers, yet the
      results are inconsistent, and the prognostic value of the receptors remains
      unclear. In the present study, we investigated the expression of ER protein and
      its correlation with clinical features of esophageal squamous cell carcinoma
      (ESCC) patients. Immunohistochemical staining for the ERs was carried out on
      paraffin-embedded primary tumor tissue sections from 89 patients with ESCC.
      Quantitative analyses were performed to determine the prognostic value of the
      expression of ERs, and Pearson's correlation was used to examine the relationship
      between ERalpha and ERbeta expression levels. Our results showed that ERalpha
      immunoreactivity was significantly lower in ESCC than that in the non-neoplastic
      epithelium (P=0.0445), whereas the ERbeta status was much stronger in ESCC than
      that in the non-neoplastic epithelium (P=0.0243). A significant inverse
      correlation was observed between ERalpha expression and depth of tumor invasion
      (P=0.0426). Correlation analysis revealed a statistically significant inverse
      correlation between the expression of ERalpha and ERbeta in ESCC (r=-0.2902,
      P=0.0058). Kaplan-Meier survival analysis showed that the patients with ERalpha
      expression (21/89) had a better outcome than patients without ERalpha expression
      (P=0.0280), whereas patients with high ERbeta immunoreactivity (44/89) were
      significantly associated with worse survival (P=0.0366). In conclusion, ERalpha
      and ERbeta levels were inversely correlated, and the downregulation of ERalpha
      and upregulation of ERbeta may indicate unfavorable prognosis of ESCC.

PMID- 24101174
TI  - Trauma: concepts and approaches.

PMID- 24101173
TI  - Higher circulating levels of OxLDL % of LDL are associated with subclinical
      atherosclerosis in female patients with systemic lupus erythematosus.
AB  - Because systemic lupus erythematosus (SLE) is associated with a high risk of
      atherosclerosis, a process that involves low-density lipoprotein (LDL) oxidation,
      we examined the hypothesis that raised fraction of LDL that is converted to
      oxidized (Ox) LDL expressed in OxLDL % of LDL (OxLDL %) is associated with the
      subclinical atherosclerosis in SLE. A cohort of 60 SLE patients with no previous
      history of cardiovascular disease had carotid artery ultrasound to identify
      plaques and to measure intima-media thickness (IMT). Forty females with
      rheumatoid arthritis (RA) were also enrolled in the study to serve as a control
      group. Plasma OxLDL concentrations were measured, and the OxLDL % of LDL were
      calculated. Traditional and SLE-related risk factors for atherosclerosis were
      evaluated. OxLDL % were significantly higher in SLE patients compared to patients
      with RA (p = 0.0311). OxLDL % were significantly higher in SLE patients with
      plaques than in those without plaques (p < 0.001). SLE patients in the highest
      IMT quartile have higher OxLDL % than patients in the lower three quartiles (p <
      0.001). The odd ratio (OR) for the OxLDL % in patients with plaques was 6.143 (p
      < 0.001) when compared to patient without plaques, while OR for the OxLDL % was
      8.34 (p < 0.001) in the patients with highest IMT quartile as compared to
      patients in the lower three quartiles after adjustment for confounding factors in
      logistic regression analysis. Our data provide evidence of an association between
      the circulating levels of OxLDL % of LDL with the risk for developing
      atherosclerosis in patients with SLE. 

PMID- 24101175
TI  - Avoiding miscommunication in acute musculoskeletal trauma cases: use of
      standardized reporting and classification schemes.
AB  - Classification schemes can be a key element of a structured radiology report,
      providing succinct guidance for clinical decision making. Classification systems
      delineate the location and morphological characteristics of fractures
      (diagnosis), may provide a graded measure of severity (prognosis), and ideally
      guide treatment options. Reports structured in this fashion optimize
      communication between the physician interpreting the examination and the
      physician directing the patient's treatment. This article reviews the concept and
      utility of standardized structured radiologic reporting based on templates or
      checklists to avoid miscommunication in the context of acute musculoskeletal
      trauma. 

PMID- 24101176
TI  - What is different in children?
AB  - The bones of infants and children are soft and so they tend to buckle and bend
      rather than frankly break. In addition, to accommodate growth, epiphyseal plates
      exist. These areas represent weak zones in the long bones and shearing/twisting
      forces cause fractures. All of this results in fractures different than what one
      sees in adults and this communication deals with how to identify these fractures,
      how to appreciate the more subtle of these fractures, and how to utilize
      comparative views for the subtle cases. 

PMID- 24101178
TI  - Imaging of acute cervical spine trauma: when to obtain which modality.
AB  - The current knowledge and evidence around the merits of different imaging
      modalities for the evaluation of cervical spine injuries are reviewed. The
      National Emergency X-Radiography Use Study, Canadian Cervical Spine rule, and
      American College of Radiology appropriateness criteria are reviewed and
      summarized. The advantages and disadvantages of available imaging modalities for
      selected cervical spine injury patterns are also illuminated to simplify the
      decision making on when to use which modality. 

PMID- 24101177
TI  - Polytrauma: optimal imaging and evaluation algorithm.
AB  - Traumatic injuries are the leading cause of death in adults < 45 years of age.
      Musculoskeletal trauma accounts for a substantial number of injuries in patients
      sustaining polytrauma. The diagnostic work-up of those patients is challenging,
      complex, and requires a structured and interdisciplinary workflow. Multidetector
      CT (MDCT) is considered the imaging modality of choice due to remarkable
      technical developments in recent years. Besides the evaluation of cranial, chest,
      and abdominal injuries, MDCT allows for integrated imaging of musculoskeletal
      trauma within a single CT examination. In this context, CT angiography
      facilitates the detection of coexisting vascular injuries after trauma of the
      skeleton. In addition, recent technologies (e.g., dual-energy CT) provide
      promising applications such as metal artifact reduction. This article summarizes
      the basic principles of interdisciplinary management of polytrauma patients,
      reviews recent advances of CT technology that have enabled comprehensive trauma
      imaging, provides appropriate scan protocols, and discusses the radiologic
      evaluation of musculoskeletal findings. 

PMID- 24101179
TI  - Assessment of acute thoracolumbar fractures: challenges in multidetector computed
      tomography and added value of emergency MRI.
AB  - Acute thoracolumbar fractures are commonly diagnosed by clinical symptoms and X
      ray plain films. Computed tomography (CT) is used to assess vertebral body
      damage, posterior wall canal intrusion, and posterior column injury. Both of
      these imaging tools have helped to develop classifications systems that aid the
      clinician in differentiating stable versus unstable spinal injuries.
      Multidetector CT has become the standard of care in polytrauma patients. It
      provides superior evaluation of bony anatomy and has been reported to be more
      cost effective than X-ray plain films, particularly in the cervicothoracic
      junction and in thoracolumbar unstable burst fractures. One disadvantage might be
      the increase in radiation exposure. Another important limitation remains the
      inability to provide adequate assessment for ligamentous injury and spinal cord
      lesions. Disc and ligaments play an important role in fracture stability because
      the failure of the posterior tension band may lead to progressive kyphosis. The
      integrity of the posterior ligamentous complex has been included in recent
      fracture classification systems and treatment algorithms. MR imaging becomes
      essential for soft tissue injury assessment, especially when including T2
      weighted sequences with fat suppression. MRI can now be considered key to
      accurate fracture classification, detection of occult and distant injuries, and
      as the basis for therapeutic decision making. It is therefore strongly
      recommended in the early assessment of spine trauma patients. 

PMID- 24101180
TI  - Diagnosis and therapy of acute hemorrhage in patients with pelvic fractures.
AB  - Within the past 15 years, significant advances in the imaging of multiorgan and
      complex trauma primarily due to the improvement of cross-sectional imaging have
      resulted in the optimization of the expedient diagnosis and management of the
      polytrauma patient. At the forefront, multidetector computed tomography (MDCT)
      has become the cornerstone of modern emergency departments and trauma centers. In
      many institutions, MDCT is the de facto diagnostic tool upon trauma activation.
      In the setting of pelvic imaging, MDCT (with its high spatial resolution and
      sensitivity as well as short acquisition times) allows for rapid identification
      and assessment of pelvic hemorrhage leading to faster triage and definitive
      management. In trauma centers throughout the world, angiography and minimally
      invasive catheter-based embolization techniques performed by interventional
      radiologists have become the standard of care for patients with acute pelvic
      trauma and related multiorgan hemorrhage. In an interdisciplinary setting,
      embolization may be performed either alone or as an adjunct procedure with open
      or closed reduction and stabilization techniques. A team-based approach involving
      multiple disciplines (e.g., radiology, traumatology, orthopedic surgery,
      intensive care medicine) is crucial to monitor and treat the actively bleeding
      patient appropriately. 

PMID- 24101181
TI  - CT-guided iliosacral screw placement.
AB  - Computed tomography (CT)-guided iliosacral screw placement for posttraumatic
      instability of that joint is a safe procedure that may be performed in a
      radiology department. CT guidance allows more accurate screw placement than
      traditional fluoroscopic imaging in the operating room. This article describes
      the technique for placing cannulated surgical screws percutaneously across the
      iliosacral joint in patients with unstable pelvic fractures using CT for
      guidance. We also discuss the pitfalls of the procedure and the complications. 

PMID- 24101182
TI  - Frequently missed findings in acute ankle injury.
AB  - Most acute ankle injuries involve the lateral ligament complex. There are several
      other structures that can be injured during acute ankle trauma and therefore can
      be responsible for the patient's acute presentation or for continuing pain. Some
      of these injuries are less common than others and thus can be more frequently
      missed during the initial patient presentation. Continued pain and disability
      following acute ankle trauma that is not responding to routine conservative
      treatment should alert the clinician and the radiologist for the possibility of
      injuries other than the common lateral ligament sprain. In this article we
      describe those injuries that are often overlooked during acute ankle assessment.
      These include the less common ankle ligaments injuries, fractures, and tendon
      related abnormalities. 

PMID- 24101183
TI  - Peripheral visual performance enhancement by neurofeedback training.
AB  - Peripheral visual performance is an important ability for everyone, and a
      positive inter-individual correlation is found between the peripheral visual
      performance and the alpha amplitude during the performance test. This study
      investigated the effect of alpha neurofeedback training on the peripheral visual
      performance. A neurofeedback group of 13 subjects finished 20 sessions of alpha
      enhancement feedback within 20 days. The peripheral visual performance was
      assessed by a new dynamic peripheral visual test on the first and last training
      day. The results revealed that the neurofeedback group showed significant
      enhancement of the peripheral visual performance as well as the relative alpha
      amplitude during the peripheral visual test. It was not the case in the non
      neurofeedback control group, which performed the tests within the same time frame
      as the neurofeedback group but without any training sessions. These findings
      suggest that alpha neurofeedback training was effective in improving peripheral
      visual performance. To the best of our knowledge, this is the first study to show
      evidence for performance improvement in peripheral vision via alpha neurofeedback
      training.

PMID- 24101184
TI  - Mechanical properties and in vitro cellular behavior of zinc-containing nano
      bioactive glass doped biphasic calcium phosphate bone substitutes.
AB  - In the present study, different amounts (0.5-5 wt%) of a sol gel-derived zinc
      containing nano-bioactive glass (NBG-Zn) powder were added to biphasic calcium
      phosphate (BCP). The mixtures were sintered at 1,100-1,300  degrees C and
      physical characteristics, mechanical properties, phase composition and morphology
      of them were studied. The samples were also soaked in human blood plasma for 15
      days to evaluate variations in their surface morphologies. Rat calvarium-derived
      osteoblastic cells were seeded on tops of various samples and cell adhesion,
      proliferation, and alkaline phosphatase activity were evaluated at different
      culturing periods. The maximum bending strength (62 MPa) was obtained for BCP
      containing 0.5 wt% NBG-Zn at temperature 1,200  degrees C. This value was
      approximately 80% higher than that of pure BCP. The bending strength failed when
      both sintering temperature and amount of added NBG-Zn increased. At 1,100 
      degrees C, NBG-Zn additive did not change the phase composition of BCP. At
      temperatures 1,200 and 1,300  degrees C, both alpha-tricalcium calcium phosphate
      (alpha-TCP) and beta-tricalcium phosphate (beta-TCP and) phases were detected.
      However, adding higher amount of NBG-Zn to BCP resulted in elevation of beta-TCP
      at 1,200  degrees C and progression of alpha-TCP at 1,300  degrees C. Based on
      the microscopic observations, adding 0.5 wt% NBG-Zn to BCP led to disappearance
      of grain boundaries, reduction of micropores and formation of a monolithic
      microstructure. No calcium phosphate precipitation was observed on sample
      surfaces after soaking in blood plasma, but some pores were produced by phase
      dissolution. The size and volume of these pores were directly proportional to NBG
      Zn content. Based on the cell studies, both BCP and NBG-Zn-added BCP samples
      supported attachment and proliferation of osteoblasts, but higher alkaline
      phosphatase enzyme was synthesized within the cells cultured on NBG-Zn-added BCP.
      Overall, biphasic calcium phosphate materials with improved mechanical and
      biological properties can be produced by using small quantity of zinc-containing
      bioactive glass particles.

PMID- 24101185
TI  - Behavior of osteoblast-like cells on calcium-deficient hydroxyapatite ceramics
      composed of particles with different shapes and sizes.
AB  - In designing the biomaterials, it is important to control their surface
      morphologies, because they affect the interactions between the materials and
      cells. We previously reported that porous calcium-deficient hydroxyapatite (HA)
      ceramics composed of rod-like particles had advantages over sintered porous HA
      ceramics; however, the effects of the surface morphology of calcium-deficient HA
      ceramics on cell behavior have remained unclear. Using a hydrothermal process, we
      successfully prepared porous calcium-deficient HA ceramics with different surface
      morphologies, composed of plate-like particles of 200-300, 500-800 nm, or 2-3 MUm
      in width and rod-like particles of 1 or 3-5 MUm in width, respectively. The
      effects of these surface morphologies on the behavior of osteoblast-like cells
      were examined. Although the numbers of cells adhered to the ceramic specimens did
      not differ significantly among the specimens, the proliferation rates of cells on
      the ceramics decreased with decreasing particle size. Our results reveal that
      controlling the surface morphology that is governed by particle shape and size is
      important for designing porous calcium-deficient HA ceramics.

PMID- 24101186
TI  - Fibrous hydrogel scaffolds with cells embedded in the fibers as a potential
      tissue scaffold for skin repair.
AB  - A novel approach was undertaken to create a potential skin wound dressing. L929
      fibroblast cells and alginate solution were simultaneously dispensed into a
      calcium chloride solution using a three-dimensional plotting system to
      manufacture a fibrous alginate scaffold with interconnected pores. These cells
      were then embedded in the alginate hydrogel fibers of the scaffold. A
      conventional scaffold with cells directly seeded on the fiber surface was used as
      a control. The encapsulated fibroblasts made using the co-dispensing method
      distributed homogeneously within the scaffold and showed the delayed formation of
      large cell aggregates compared to the control. The cells embedded in the hydrogel
      fibers also deposited more type I collagen in the extracellular matrix and
      expressed higher levels of fgf11 and fn1 than the control, indicating increased
      cellular proliferation and attachment. The results indicate that the novel co
      dispensing alginate scaffold may promote skin regeneration better than the
      conventional directly-seeded scaffold. 

PMID- 24101187
TI  - Intraosseous structural graft technique: a new surgical concept in the treatment
      of superolateral defects in case of dysplastic acetabulum, during hip replacement
      surgery biomechanical and cadaver experimentations.
AB  - PURPOSE: The replacement of the dysplastic hip, despite the numerous available
      surgical techniques, is not entirely solved. One of the reasons for this is the
      relative lack of bone in the acetabulum. In this study, we present a new concept
      (intraosseous structural graft technique), with the aim to improve the primary
      stability and biological environment of the graft. METHODS: During the procedure
      in the cranial quadrant of the acetabulum, a proximally hinged cortico-spongious
      plate is fashioned that is opened laterally and a wedge-shaped graft made from
      the femoral head is impacted. The precisely fitted graft has good primary
      rotational and cranial stability which is further improved by a bicortical screw.
      RESULTS: The hypothesis is supported by examination on 3D models. Cadaver
      experimentations were performed on 19 hips of 10 cadavers, and stability testing
      was done on a further 20 hips of 10 cadavers with a material testing apparatus.
      Also the analysis of the biological and mechanical properties of the graft and
      the implant were examined. CONCLUSION: Based on our results, it can be concluded
      that our technique provides good primary stability with a more favorable
      biological condition for bony incorporation compared to other bulk bone graft
      techniques.

PMID- 24101188
TI  - Emerging intra-articular causes of groin pain in athletes.
AB  - Groin pain remains one of the most poorly understood conditions in clinical
      sports medicine. It may be caused by either extra-articular or intra-articular
      conditions. While extra-articular causes have been extensively studied and
      reasonably understood, a number of elusive intra-articular causes are emerging,
      many of which were previously unknown and therefore undiagnosed, leading to
      premature ending of many competitive careers. This article makes an attempt to
      look at various, elusive intra-articular causes of groin pain in athletes. This
      article also analyses the currently available evidence on trends in diagnosis and
      treatment for these conditions. 

PMID- 24101189
TI  - The role of mesenchymal stem cells in bone repair and regeneration.
AB  - Despite the undisputed modern development of synthetic biomaterials that range
      from bioactive unresorbable to restorable materials, clinically applied
      osteoconduction bone substitutes still have limitations in the treatment of bone
      defects. These are the result of the physical and chemical properties of the
      utilized materials and the biological interactions associated with both local and
      general reactions of the organism. Mesenchymal stem cells constitute a promising
      treatment alternative in orthopedics. Preclinical studies regarding the use of
      mesenchymal stem cells have shown good therapeutic results. However, it is still
      necessary to advance further in this area and enable the treatment of patients
      with critically large bone defects. The aim of this review is to describe the
      role of mesenchymal stem cells in bone repair and regeneration, describe the
      techniques used in the clinical application of mesenchymal stem cells and outline
      future research endeavors in this area. 

PMID- 24101190
TI  - Prognostic and clinicopathological significance of survivin expression in bladder
      cancer patients: a meta-analysis.
AB  - Survivin has been widely reported to play a role in diagnosis and prognosis of
      bladder cancer patients. However, published data on this subject are
      heterogeneous. Here, we conducted a meta-analysis to obtain a complete evaluation
      of the association between survivin and recurrence-free survival (RFS), disease
      specific survival (DSS), overall survival (OS), and odds ratio (OR) in bladder
      cancer patients. Published studies on this subject were selected for further
      assessment by online articles in PubMed, MEDLINE, EMBASE, and OVID databases.
      Pooled hazard ratios (HR) with 95 % confidence interval (95 % CI) were estimated.
      Funnel plots were used to evaluate the publication bias. As well, heterogeneity
      and sensitivity were analyzed. In this meta-analysis, we included 13 studies with
      the total number of 1,963 patients. Positive survivin expression in bladder
      cancer was associated with a poor RFS (HR, 1.831; 95 % CI, 1.344-2.49), DSS (HR,
      1.721; 95 % CI, 1.477-2.004), or OS (HR, 1.753; 95 % CI, 1.092-2.816) in
      patients. In addition, a significant association between expression of survivin
      and age (OR, 0.641; 95 % CI, 0.416-0.987) as well as stage (OR, 0.37; 95 % CI,
      0.190-0.750) was revealed. Heterogeneity was observed among the included studies
      with RFS (x (2) =29.58, p = 0.009, I (2) = 52.7 %), OS (x (2) = 15.67, p = 0.008,
      I (2) = 68.1 %), and stage (x (2) = 11.97, p = 0.035, I (2) = 58.2 %). There was
      no publication bias according to Begg's and Egger's tests except for studies with
      gender. Furthermore, sensitivity analysis obtained the source of heterogeneity
      and confirmed opposite results of some studies. This study suggests that
      expression of survivin indicates poor prognosis in older patients and muscle
      invasive or advanced stage in bladder cancer. Survivin expression could be used
      in identifying a subgroup of patients with potential to benefit from a targeted
      therapy against survivin.

PMID- 24101191
TI  - High-level expression of CXCR4 in breast cancer is associated with early distant
      and bone metastases.
AB  - Metastasis is the most life-threatening complication in all cancers. The
      chemokine receptor 4 (CXCR4) is expressed at high levels in many breast-cancer
      tumors and may modulate metastasis. We compared the time-to-metastasis and the
      sites of metastasis between breast-cancer tumors expressing CXCR4 at high or low
      levels. We enrolled 191 early breast cancer patients in our study. The expression
      of CXCR4 was evaluated using immunohistochemical staining, and the patients were
      divided into low-level (CXCR4-) and high-level (CXCR4+) CXCR4 expression groups.
      Associations between the patients' level of CXCR4 expression and their basic
      clinical characteristics, time-to-metastasis, and metastatic sites were examined
      using a Cox proportional-hazards regression model. A total of 107 CXCR4+ patients
      (56 %) were identified. No statistical differences were evident in basic
      characteristics between the CXCR4+ and CXCR4- groups. The CXCR4+ group had a
      higher incidence of distant metastasis during the first year (10.3 % versus 1.1
      %, P = 0.009) and shorter event-free survival (17.43 months versus 27.5 months, P
      = 0.026) than those of the CXCR4- group. The CXCR4+ group also had a higher
      incidence of bone metastasis (P = 0.008) than the CXCR4- group. No significant
      difference in metastasis sites in other organs was observed between the two
      groups. A high level of CXCR4 expression in breast cancer is associated with
      early distant and bone metastases. The CXCR4+ phenotype may be a useful predictor
      for the prevention of early treatment failure and bone metastasis in breast
      cancer patients. This retrospective study shows that a high expression of CXCR4
      in breast cancer is associated with earlier distant metastasis and bone
      metastasis in breast cancer.

PMID- 24101192
TI  - XPD Asp312Asn and Lys751Gln polymorphisms and breast cancer susceptibility: a
      meta-analysis.
AB  - The association between xeroderma pigmentosum complementation group D (XPD)
      Asp312Asn and Lys751Gln gene polymorphisms and breast cancer risk has been widely
      reported, but the results were inconsistent. In order to derive a more precise
      estimation of the relationship, a meta-analysis was performed. A comprehensive
      search strategy was conducted towards the electronic databases including Medline,
      PubMed, Web of Science, Embase, and Chinese Biomedical Literature Database
      (Chinese). The association between the XPD polymorphism and breast cancer risk
      was conducted by odds ratios (ORs) and 95% confidence intervals (95% CIs). A
      total of 22 studies with 18,136 cases and 18,351 controls were included in our
      meta-analysis. Among these, 12 studies with 7,667 cases and 7,480 controls for
      Asp312Asn polymorphism and 20 studies with 10,469 cases and 10,871 controls for
      Lys751Gln polymorphism. With regard to Asp312Asn polymorphism, no significantly
      associated was found with breast cancer risk. However, significant association
      was found between Lys751Gln polymorphism and breast cancer risk under all genetic
      models in overall populations (C vs. A-OR = 1.10, 95% CI = 1.04-1.17, P = 0.002;
      CC vs. AA-OR = 1.17, 95% CI = 1.06-1.30, P = 0.003; AC vs. AA-OR = 1.06, 95% CI =
      1.01-1.12, P = 0.032; CC vs. AC/AA-OR = 1.17, 95% CI = 1.04-1.32, P = 0.009;
      CC/AC vs. AA-OR = 1.07, 95% CI = 1.02-1.12, P = 0.005). In subgroup analysis base
      on ethnicity, significance was found in Caucasians and mix. The results suggest
      that XPD Asp312Asn polymorphism was not associated with breast cancer. The XPD
      Lys751Gln polymorphism significantly increased breast cancer risk, especially for
      Caucasian and mix.

PMID- 24101193
TI  - The association of interleukin-16 gene polymorphisms with IL-16 serum levels and
      risk of nasopharyngeal carcinoma in a Chinese population.
AB  - Interleukin (IL)-16 plays a fundamental role in inflammatory diseases, as well as
      in the development and progression of tumors. Genetic variation in DNA sequence
      of IL16 gene may lead to altered cytokine production and/or activity, and this
      variation may modulate an individual's susceptibility to nasopharyngeal carcinoma
      (NPC). To test this hypothesis, we investigated the association of IL16 gene
      polymorphisms and serum IL-16 levels with NPC risk in a Chinese population. We
      analyzed IL16 gene rs11556218 T/G, rs4778889 T/C, and rs4072111 C/T polymorphisms
      using PCR-RFLP and DNA sequencing, and serum IL-16 levels were measured by ELISA.
      The IL16 rs11556218 T/G polymorphism was significantly associated with the
      susceptibility to NPC patients. The TG genotype was associated with a
      significantly higher risk of NPC as compared with the TT genotype (OR = 2.05, 95%
      CI 1.04-4.01; p = 0.037). Patients carrying the G allele had a significantly
      higher risk for developing NPC compared with individuals carrying the T allele
      (OR = 1.79, 95% CI 1.07-3.01; p = 0.027). The serum IL-16 levels were increased
      in NPC patients compared with controls (p < 0.01); the genotypes carrying the
      IL16 rs11556218 G variant allele were associated with increased serum IL-16
      levels compared with the homozygous wild-type genotype in NPC patients (all p
      values <0.01). Our data suggested that IL16 rs11556218 T/G polymorphism was
      associated with increased susceptibility to NPC through increasing the production
      of serum IL-16 levels.

PMID- 24101194
TI  - Long-term intraocular pressure changes after vitrectomy for epiretinal membrane
      and macular hole.
AB  - BACKGROUND: To investigate long-term intraocular pressure (IOP) changes after
      vitrectomy for epiretinal membrane (ERM) or macular hole (MH). METHODS: We
      retrospectively reviewed the medical records of 57 eyes with ERM and 61 eyes with
      MH that underwent vitrectomy. IOP levels and changes at 1, 3, 6, 12 months, and
      the final visit from baseline were evaluated in vitrectomized eyes and non
      vitrectomized fellow eyes. RESULTS: In the ERM group, the mean follow-up period
      was 29.3 months; the mean preoperative IOP in the operated eyes was 12.9 +/- 2.5
      mmHg and the final IOP was 13.2 +/- 2.9 mmHg. In the MH group, the mean follow-up
      period was 25.6 months; the mean preoperative IOP in the operated eyes was 13.3
      +/- 2.5 mmHg and the final IOP was 14.0 +/- 3.2 mmHg. The mean final IOP of the
      fellow unoperated eyes was 13.0 +/- 2.5 mmHg in the ERM group and it was 12.9 +/-
      3.2 mmHg in the MH group. A significant difference was found between the operated
      eyes and fellow eyes at the final visit in the MH group (P < 0.01) but not in the
      ERM group (P = 0.40). MH group was significantly at high risk of IOP increase
      after vitrectomy (P < 0.01). CONCLUSIONS: IOP increase after vitrectomy was found
      in some eyes with MH during long-term follow-up but it was unlikely in eyes with
      ERM.

PMID- 24101196
TI  - Endovascular treatment of 170 consecutive cranial dural arteriovenous fistulae:
      results and complications.
AB  - This study aims to evaluate a single-center experience with endovascular
      treatment of cranial dural arterievenous fistulae (CDAVF). The clinical and
      radiological records of 170 consecutive patients harboring a CDAVF and treated
      endovascularly in a 16-year period were reviewed. A variety of data related to
      demographics, features of the lesion, treatment, outcome, and follow-up were
      analyzed with emphasis to the results and complications. Half of the lesions had
      cortical venous drainage (CVD) in the initial angiographic investigation, whereas
      26 % had exclusively CVD. Sixty-seven percent of our patients presented with
      benign symptoms and 33 % with aggressive symptoms. In 60.5 % of the patients with
      benign lesion (without CVD), an anatomic cure in the immediate postinterventional
      angiogram without complication or permanent morbidity was achieved, whereas 69 %
      of the patients with aggressive lesions (with CVD) had an anatomic cure in the
      postinterventional final angiogram with all permanent-morbidity cases belonging
      to this group. The average of endovascular operation sessions per patient was
      1.2. In a mean follow-up period of 2.8 years, the overall complete occlusion rate
      was 85.5 % (78 % for the benign group and 89.5 % for the aggressive group) and
      clinical cure and/or improvement rate of 93 %. The operative mortality was zero,
      and permanent neurologic morbidity was 2.3 %. In 73 % of our cases, N-butyl
      cyanoacrylate (NBCA) was used as the only or main embolic material. Endovascular
      embolization is the treatment of choice for CDAVF. High rates of good anatomical
      and clinical results, associated with very low operative complication rate can be
      achieved with few embolization sessions. Although mastering of a permanent
      embolic material is important, the therapeutic strategy should be individulized
      and not material based. 

PMID- 24101197
TI  - Bone marrow deficiency of TRPC3 channel reduces early lesion burden and necrotic
      core of advanced plaques in a mouse model of atherosclerosis.
AB  - AIMS: Macrophage apoptosis plays a determinant role in progression of
      atherosclerotic lesions. An important goal in atherosclerosis research is to
      identify new components of macrophage apoptosis that can eventually be exploited
      as molecular targets in strategies aimed at manipulating macrophage function in
      the lesion. In the previous work from our laboratory, we have shown that
      transient receptor potential canonical 3 (TRPC3) channel is an obligatory
      component of survival mechanisms in human and murine macrophages and that TRPC3
      deficient non-polarized bone marrow-derived macrophages exhibit increased
      apoptosis, suggesting that in vivo TRPC3 might influence lesion development. In
      the present work, we used a bone marrow transplantation strategy as a first
      approach to examine the impact of macrophage deficiency of TRPC3 on early and
      advanced atherosclerotic lesions of Apoe(-/-) mice. METHODS AND RESULTS: After 3
      weeks of high-fat diet, lesions in mice transplanted with bone marrow from Trpc3(
      /-) donors were smaller and with reduced cellularity than controls. Advanced
      lesions from these mice exhibited reduced necrotic core, less apoptotic
      macrophages, and increased collagen content and cap thickness. In vitro, TRPC3
      deficient macrophages polarized to the M1 phenotype showed reduced apoptosis,
      whereas both M1 and M2 macrophages had increased efferocytic capacity.
      CONCLUSIONS: Bone marrow deficiency of TRPC3 has a dual beneficial effect on
      lesion progression by reducing cellularity at early stages and necrosis in the
      advanced plaques. Our findings represent the first evidence for a role of a
      member of the TRPC family of cation channels in mechanisms associated with
      atherosclerosis.

PMID- 24101198
TI  - Intra- and intermodal integration of discrepant visual and proprioceptive action
      effects.
AB  - Integration of discrepant visual and proprioceptive action effects puts high
      demands on the human information processing system. The present study aimed to
      examine the integration mechanisms for the motor (Exp. 1) and visual modality
      (Exp. 2). According to theories of common coding, we assumed that visual as well
      as proprioceptive information is represented within the same cognitive domain and
      is therefore likely to affect each other (multisensory cross talk). Thus, apart
      from the often-confirmed visual dominance in multisensory integration, we asked
      about intra- and intermodal recall of either proprioceptive or visual information
      and whether there were any differences between the motor and visual modality. In
      a replication paradigm, we perturbed the relation between hand movements and
      cursor movements. The task required the (intra- vs. intermodal) replication of an
      initially performed (seen) hand (cursor) movement in a subsequent motor (visual)
      replication phase. First, mechanisms of integration were found to be dependent on
      the output modality. Visual action effects interfered the motor modality, but
      proprioceptive action effects did not have any effects on the visual modality.
      Second, however, intermodal integration was more susceptible to interference, and
      this was found to be independent from the output modality. Third, for the motor
      modality, the locus of perturbation (perturbation of cursor amplitude or
      perturbation of hand amplitude) was irrelevant, but for the visual modality,
      perturbation of hand amplitudes reduced the cross talk. Tool use is one field of
      application of these kinds of results, since the optimized integration of
      conflicting action effects is a precondition for using tools successfully. 

PMID- 24101200
TI  - Myeloid sarcoma of the nasopharynx mimicking an aggressive lymphoma.
AB  - BACKGROUND: Myeloid sarcoma (MS) is a rare extra-medullary tumour of the myeloid
      lineage, which can be a difficult diagnosis to make. CASE PRESENTATION: We report
      the case of a 73-year-old male with a right-sided nasopharyngeal mass revealed on
      CT scan and MRI. RESULTS: An initial cytological and histological examination
      suggested a high-grade lymphoma. Nevertheless, the final diagnosis was a MS with
      an unusual involvement of the nasopharynx that was treated with a conventional
      induction leukemia therapy. Eight months later, the patient had persistent
      thrombocytopenia and a bone marrow aspiration showed the dysplasia of a high
      grade myelodysplastic syndrome and cytogenetics detected t(3;21). The patient was
      treated with a 5-Azacitidine (Vidaza) protocol until overt progression and
      disease evolution. CONCLUSION: In conclusion few cases of MS involving the
      nasopharynx have been reported. Its diagnosis is often difficult and should be
      considered especially when a high index of suspicion is present and the
      immunophenotype of the malignant haematological cells is not clearly in favour of
      a lymphoma.

PMID- 24101199
TI  - New molecular staging with G-factors (VEGF-C and Reg IV) by supplementing TNM
      classification in colorectal cancers.
AB  - Staging classification of colorectal cancers is performed by the UICC/TNM
      classification system, which is the global gold standard. However, we often
      experience in clinical practice that there are considerable differences in
      prognoses between patients who have the same classification particularly in stage
      II and III cancers. The aim of this study was to propose a new TNM-G
      classification to predict prognosis and recurrence by supplementing the
      conventional TNM classification. A total of 220 cases of colorectal cancer,
      including 77 at stage II and 143 at stage III, were registered from four
      independent facilities. Immunohistochemical staining for 7 molecules, such as
      p53, vascular endothelial growth factor (VEGF)-A, VEGF-C, regenerating islet
      derived family, member 4 (Reg IV), olfactomedin 4, Claudin-18 and matrix
      metalloproteinase-7 (MMP-7), was performed to investigate the correlation between
      clinicopathological factors and expression of each molecule. Based on the
      results, no significant correlation was observed between the immunostaining
      expression of these 7 factors and recurrence in total colorectal cancer.
      Recurrence in stage II (77 cases) was significantly higher in cases positive for
      Reg IV expression (P=0.042). On analysis of overall survival (OS) and disease
      free survival (DFS), VEGF-C and Reg IV expression had a correlation with poor
      prognosis, therefore, these factors were selected and applied to G-factor
      classifications so that cases negative for both could be classified as G0, cases
      positive for either of the factors could be classified as G1, and cases positive
      for both factors could be classified as G2. While no significant correlation was
      observed in the recurrence rates between G0 and G2, OS and DFS in stage II cases
      were significantly poorer for G2 cases in comparison with G0 or G1 cases. The
      survival curves of OS and DFS in stage II G2 were similar to that of stage III
      cases. According to these results, prognosis of VEGF-C/Reg IV both positive G2
      cases in stage II colorectal cancer was found to be almost equal to the poor
      survival in stage III cases, and the advancement of one stage up migration based
      on G-factors may be supposed to be highly feasible for clinical application. In
      conclusion, the combination of VEGF-C and Reg IV may be a promising factor for
      clinical staging to supplement the classical TNM classification system, and it
      may suggest a good indication of adjuvant chemotherapy for G2 cases in stage II
      colorectal cancers.

PMID- 24101201
TI  - Genetic evidence that Arabidopsis ALTERED ROOT ARCHITECTURE encodes a putative
      dehydrogenase involved in homoserine biosynthesis.
AB  - KEY MESSAGE: Genetic and molecular analysis of an Arabidopsis root development
      mutant identified a putative dehydrogenase gene involved in homoserine
      biosynthesis. In higher plants, homoserine (Hse) is derived from aspartate (Asp)
      and is an important intermediate for production of methionine (Met), threonine
      (Thr), and isoleucine (Ile). In Arabidopsis, six enzymes involved in the
      biosynthesis of Hse from Asp have been well characterized. It is not known,
      however, whether there exist other enzymes involved in this process. In this
      work, we characterized an Arabidopsis mutant, ara (altered root architecture),
      with a short primary root and an increased number of lateral roots. Genetic and
      molecular analysis indicated that the ARA gene encodes a protein with a D-isomer
      specific 2-hydroxyacid dehydrogenase domain. ARA is expressed in all plant organs
      and is localized in the cell periphery. The ara mutant phenotypes can be rescued
      by exogenously applied Hse, Met, Ile and 2-oxobutanoate. Based on the results
      presented here, we propose that the ARA protein may be a dehydrogenase involved
      in homoserine biosynthesis.

PMID- 24101202
TI  - Management of radiation-induced rectal bleeding.
AB  - Pelvic radiation disease is one of the major complication after radiotherapy for
      pelvic cancers. The most commonly reported symptom is rectal bleeding which
      affects patients' quality of life. Therapeutic strategies for rectal bleeding are
      generally ignored and include medical, endoscopic, and hyperbaric oxygen
      treatments. Most cases of radiation-induced bleeding are mild and self-limiting,
      and treatment is normally not indicated. In cases of clinically significant
      bleeding (i.e. anaemia), medical therapies, including stool softeners, sucralfate
      enemas, and metronidazole, should be considered as first-line treatment options.
      In cases of failure, endoscopic therapy, mainly represented by argon plasma
      coagulation and hyperbaric oxygen treatments, are valid and complementary second
      line treatment strategies. Although current treatment options are not always
      supported by high-quality studies, patients should be reassured that treatment
      options exist and success is achieved in most cases if the patient is referred to
      a dedicated centre. 

PMID- 24101203
TI  - Expression and purification of recombinant human serum albumin from selectively
      terminable transgenic rice.
AB  - Human serum albumin (HSA) is widely utilized for medical purposes and biochemical
      research. Transgenic rice has proved to be an attractive bioreactor for mass
      production of recombinant HSA (rHSA). However, transgene spread is a major
      environmental and food safety concern for transgenic rice expressing proteins of
      medical value. This study aimed to develop a selectively terminable transgenic
      rice line expressing HSA in rice seeds, and a simple process for recovery and
      purification of rHSA for economical manufacture. An HSA expression cassette was
      inserted into a T-DNA vector encoding an RNA interference (RNAi) cassette
      suppressing the CYP81A6 gene. This gene detoxifies the herbicide bentazon and is
      linked to the 5-enolpyruvylshikimate-3-phosphate synthase (EPSPS) cassette which
      confers glyphosate tolerance. ANX Sepharose Fast Flow (ANX FF) anion exchange
      chromatography coupled with Butyl Sepharose High Performance (Butyl HP)
      hydrophobic interaction chromatography was used to purify rHSA. A transgenic rice
      line, HSA-84, was obtained with stable expression of rHSA of up to 0.72% of the
      total dry weight of the dehusked rice seeds. This line also demonstrated high
      sensitivity to bentazon, and thus could be killed selectively by a spray of
      bentazon. A two-step chromatography purification scheme was established to purify
      the rHSA from rice seeds to a purity of 99% with a recovery of 62.4%. Results
      from mass spectrometry and N-terminus sequencing suggested that the purified rHSA
      was identical to natural plasma-derived HSA. This study provides an alternative
      strategy for large-scale production of HSA with a built-in transgene safety
      control mechanism. 

PMID- 24101204
TI  - Genetic variability and evolution of rice stripe virus.
AB  - Rice stripe virus (RSV) is the type member of the genus Tenuivirus. RSV is known
      to have four segmented, single-stranded RNA molecules and causes rice stripe
      disease in the rice fields of China, Japan, and Korea. Based on the complete
      genomic sequences of the determined 6 RSV isolates (from Yunnan, Jiangsu,
      Zhejiang, and Liaoning Provinces, China) and 27 other RSV isolates (from Yunnan,
      Jiangsu, Anhui, Henan, and Shandong Provinces of China, also Japan and Korea)
      downloaded from GenBank, we provided a genotyping profile of RSV field isolates
      and described the population structure of RSV. All RSV isolates, except isolate
      CX, could be divided into two subtypes, one including 6 isolates from Yunnan
      Province, and the other including 26 isolates from different parts of China,
      Japan, and Korea, which were referred to as subtype II and subtype I,
      respectively. The amino acid distances between subtypes range from 0.053 to
      0.085. RSV isolates in Yunnan Province were genetically differentiated from other
      parts of China, Japan, and Korea and showed infrequent gene flow. The RSV
      populations collected from other parts of China, Japan, and Korea were only
      composed of subtype I and showed very low genetic diversity. We speculated that
      isolate CX may be the result of recombination of isolates from two subtypes. Two
      potential recombination events were detected in RNA4 of isolate CX. 

PMID- 24101205
TI  - Quantitative changes of nitrergic neurons during postnatal development of chicken
      myenteric plexus.
AB  - OBJECTIVE: Information regarding the development of the enteric nervous system
      (ENS) is important for understanding the functional abnormalities of the gut.
      Because fertilized chicken eggs provide easy access to embryos, chicken models
      have been widely used to study embryonic development of myenteric plexus;
      however, no study has been focused on the postnatal period. The aim of this study
      was to perform a qualitative and quantitative analysis of the nitrergic neurons
      in the myenteric plexus of developing chickens in the postnatal period. METHODS:
      Whole-mount preparations of the myenteric plexus were made in 7-d, 15-d, and 40-d
      old (adult) chickens of either sex (n=15). The myenteric plexus was studied after
      nicotinamide adenine dinucleotide phosphate diaphorase (NADPH-d) histochemistry
      using light microscopy, digital photography, and Image-Pro Plus 6.0 software. The
      numbers of positively stained neurons and ganglia were counted in the duodenum,
      jejunum, ileum, caecum, and colon in the different age groups. Data were
      expressed as mean+/-standard deviation (SD), and statistical analysis was
      performed using a one-way analysis of variance (ANOVA) test. RESULTS: The
      positively stained neurons showed various morphologies and staining intensities,
      and formed bead-shaped and U-shaped arrangements in the myenteric plexus. The
      densities of neurons and ganglia increased with age. However, the number of
      positive neurons per ganglion increased. The number of NADPH-d-positive neurons
      was highest in the colon, followed by the ileum, the jejunum, the duodenum, and
      the caeca in all age groups. CONCLUSIONS: Developmental changes in the myenteric
      plexus of chickens continue in the postnatal period, indicating that the
      maturation process of the gastrointestinal function is gradual. In addition, no
      significant difference is happening among different intestinal segments during
      postnatal development, suggesting that the function of different intestinal
      segments had been determined after birth.

PMID- 24101206
TI  - Meat quality traits of four Chinese indigenous chicken breeds and one commercial
      broiler stock.
AB  - Meat quality traits of four genotypes of Chinese indigenous chicken [Ninghai
      chicken (NC), frizzle chicken (FC), Ninghai xiang chicken (XC), and Zhenning
      loquat chicken (LC)] and one genotype of commercial broiler [Arbor Acres plus
      broiler (AAB)] were analyzed. The indigenous chickens were raised before the
      commercial chickens in order to achieve the same final processed days. Indigenous
      chickens of NC, FC, XC, and LC showed significantly higher inosine-5'
      monophosphate (IMP) content, shorter fiber diameter, and lower shear force than
      those of AAB (P<0.05). In the indigenous genotypes, NC and FC had significantly
      shorter fiber diameters and lower shear forces than XC and LC (P<0.05), and NC
      and XC had a higher IMP content than FC and LC (P<0.05). Moreover, the indigenous
      genotype of LC significantly displayed the highest protein content (P<0.05) in
      the five genotypes of birds, and no significant differences of protein content
      were found between the other genotypes of NC, FC, XC, and AAB (P>0.05). The
      indigenous chickens from FC displayed the highest total lipid content in the five
      bird genotypes (P<0.05). Significant differences of pH, color values of L* and
      a*, and drip loss for the five genotypes of birds were also observed. In
      conclusion, there were significant differences in the meat quality traits of the
      bird breeds selected in this study, and the indigenous chickens, especially the
      NC genotype, produced better quality meat as far as the IMP content, fiber
      diameters, and shear forces were concerned. 

PMID- 24101207
TI  - Optimization of extraction of phenolics from leaves of Ficus virens.
AB  - In this research, the conditions for extraction of phenolics from leaves of Ficus
      virens were optimized using response surface methodology (RSM). The extraction
      abilities of phenolics (EAP) and flavonoids (EAF), the 2,2-diphenyl-1
      pierylhydrazyl (DPPH) free-radical scavenging potential, and the ferric
      reducing/antioxidant power (FRAP) were used as quality indicators. The results of
      single-factor experiments showed that temperature, ethanol concentration,
      extraction time, and the number of extraction cycles were the main influencing
      variables, and these provided key information for the central composite design.
      The results of RSM fitted well to a second degree polynomial model and more than
      98% of the variability was explained. The ideal extraction conditions for EAP,
      EAF, DPPH free-radical scavenging potential, and FRAP were obtained. Considering
      the four quality indicators overall, the ideal extraction conditions were 58%
      ethanol at 57  degrees C for 37 min with three extraction cycles. At the ideal
      extraction conditions, the values of EAP, EAF, DPPH free-radical scavenging
      potential, and FRAP were 5.72%, 3.09%, 58.88 mg ascorbic acid equivalent (AAE)/g
      dry weight (DW), and 15.86 mg AAE/g DW, respectively. In addition, linear
      correlations were observed between EAP, EAF, and antioxidant potential. 

PMID- 24101208
TI  - Identification of miRNAs and their targets in tea (Camellia sinensis).
AB  - MicroRNAs (miRNAs) are endogenous small RNAs playing a crucial role in plant
      growth and development, as well as stress responses. Among them, some are highly
      evolutionally conserved in the plant kingdom, this provide a powerful strategy
      for identifying miRNAs in a new species. Tea (Camellia sinensis) is one of the
      most important commercial beverage crops in the world, but only a limited number
      of miRNAs have been identified. In the present study, a total of 14 new C.
      sinensis miRNAs were identified by expressed sequence tag (EST) analysis from
      47452 available C. sinensis ESTs. These miRNAs potentially target 51 mRNAs, which
      can act as transcription factors, and participate in stress response,
      transmembrane transport, and signal transduction. Analysis of gene ontology (GO),
      based on these targets, suggested that 37 biological processes were involved,
      such as oxidation-reduction process, stress response, and transport. Kyoto
      Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis inferred
      that the identified miRNAs took part in 13 metabolic networks. Our study will
      help further understanding of the essential roles of miRNAs in C. sinensis growth
      and development, and stress response. 

PMID- 24101209
TI  - A pilot scale trickling filter with pebble gravel as media and its performance to
      remove chemical oxygen demand from synthetic brewery wastewater.
AB  - Evaluating the performance of a biotrickling filter for the treatment of
      wastewaters produced by a company manufacturing beer was the aim of this study. A
      pilot scale trickling filter filled with gravel was used as the experimental
      biofilter. Pilot scale plant experiments were made to evaluate the performance of
      the trickling filter aerobic and anaerobic biofilm systems for removal of
      chemical oxygen demand (COD) and nutrients from synthetic brewery wastewater.
      Performance evaluation data of the trickling filter were generated under
      different experimental conditions. The trickling filter had an average efficiency
      of (86.81+/-6.95)% as the hydraulic loading rate increased from 4.0 to 6.4
      m(3)/(m(2)?d). Various COD concentrations were used to adjust organic loading
      rates from 1.5 to 4.5 kg COD/(m(3)?d). An average COD removal efficiency of
      (85.10+/-6.40)% was achieved in all wastewater concentrations at a hydraulic
      loading of 6.4 m(3)/(m(2)?d). The results lead to a design organic load of 1.5 kg
      COD/(m(3)?d) to reach an effluent COD in the range of 50-120 mg/L. As can be
      concluded from the results of this study, organic substances in brewery
      wastewater can be handled in a cost-effective and environmentally friendly manner
      using the gravel-filled trickling filter. 

PMID- 24101210
TI  - Multi-year monitoring of paddy rice planting area in Northeast China using MODIS
      time series data.
AB  - The objective of this study was to investigate the tempo-spatial distribution of
      paddy rice in Northeast China using moderate resolution imaging spectroradiometer
      (MODIS) data. We developed an algorithm for detection and estimation of the
      transplanting and flooding periods of paddy rice with a combination of enhanced
      vegetation index (EVI) and land surface water index with a central wavelength at
      2130 nm (LSWI2130). In two intensive sites in Northeast China, fine resolution
      satellite imagery was used to validate the performance of the algorithm at pixel
      and 3*3 pixel window levels, respectively. The commission and omission errors in
      both of the intensive sites were approximately less than 20%. Based on the
      algorithm, annual distribution of paddy rice in Northeast China from 2001 to 2009
      was mapped and analyzed. The results demonstrated that the MODIS-derived area was
      highly correlated with published agricultural statistical data with a coefficient
      of determination (R(2)) value of 0.847. It also revealed a sharp decline in 2003,
      especially in the Sanjiang Plain located in the northeast of Heilongjiang
      Province, due to the oversupply and price decline of rice in 2002. These results
      suggest that the approaches are available for accurate and reliable monitoring of
      rice cultivated areas and variation on a large scale. 

PMID- 24101211
TI  - Microspectroscopic Study of Liposome-to-cell Interaction Revealed by Forster
      Resonance Energy Transfer.
AB  - We report the Forster resonance energy transfer (FRET)-labeling of liposomal
      vesicles as an effective approach to study in dynamics the interaction of
      liposomes with living cells of different types (rat hepatocytes, rat bone marrow,
      mouse fibroblast-like cells and human breast cancer cells) and cell organelles
      (hepatocyte nuclei). The in vitro experiments were performed using fluorescent
      microspectroscopic technique. Two fluorescent dyes (DiO as the energy donor and
      DiI as an acceptor) were preloaded in lipid bilayers of phosphatidylcholine
      liposomes that ensures the necessary distance between the dyes for effective
      FRET. The change in time of the donor and acceptor relative fluorescence
      intensities was used to visualize and trace the liposome-to-cell interaction. We
      show that FRET-labeling of liposome vesicles allows one to reveal the differences
      in efficiency and dynamics of these interactions, which are associated with
      composition, fluidity, and metabolic activity of cell plasma membranes. 

PMID- 24101212
TI  - The apoptosis of peripheral blood lymphocytes promoted by hyperbaric oxygen
      treatment contributes to attenuate the severity of early stage acute pancreatitis
      in rats.
AB  - The aim of this study was to investigate the immunoregulatory effects of
      hyperbaric oxygen (HBO) via promoting the apoptosis of peripheral blood
      lymphocytes (PBLs) to attenuate the severity of early stage acute pancreatitis
      (AP) in rats. Additionally, the persistence of the HBO treatment effects was
      evaluated. One hundred and twenty male Wistar rats were randomized into four
      groups: sham, AP, AP + normobaric oxygen (NBO), and AP + HBO. Each group
      consisted of 30 rats. Four hours after the induction of AP, the 30 rats in the AP
      + NBO group were given normobaric oxygen treatment with 100 % oxygen at 1 atm for
      90 min. The 30 rats in the AP + HBO group received 100 % oxygen at 2.5 atm for 90
      min, with a compression/decompression time of 15 min. The 30 rats in the AP group
      remained untreated. At 6, 12, and 24 h after the induction of AP, surviving rats
      from each group were sacrificed, and the blood and tissue samples were collected
      for the following measurements: the partial pressure of oxygen (PaO2) and oxygen
      saturation (SaO2) of the arterial blood, the levels of serum amylase, lipase,
      interleukin-2 (IL-2), interferon-gamma (IFN-gamma), interleukin-10 (IL-10),
      hepatocyte growth factor (HGF), and reactive oxygen species (ROS), and the
      mitochondrial membrane potential (?Psim) of the PBLs. The expression levels of
      procaspase-3, caspase-3, procaspase-9, and caspase-9 were also evaluated in the
      PBLs. Additionally, the apoptosis of PBLs was assessed, and the pancreatic
      tissues were subjected to a histopathological analysis by pathological grading
      and scoring. The histopathology of the lung, liver, kidney, duodenum, and heart
      was also analyzed at 12 h after the induction of AP. Significant differences were
      found at 6 and 12 h after AP induction. The HBO treatment significantly elevated
      the PaO2 and SaO2 levels, and the ROS levels in the PBLs. Additionally, HBO
      downregulated the levels of amylase and lipase. The HBO treatment also reduced
      the ?Psim levels, upregulated the expression of caspase-3 and caspase-9, and
      increased the apoptosis rate of the PBLs. Moreover, the HBO treatment decreased
      the serum concentrations of IL-2, IFN-gamma and HGF, and reduced the pathological
      scores of the pancreatic tissue. The histopathological changes of the lung,
      liver, kidney, duodenum, and heart were also improved. A significant elevation of
      IL-10 occurred only at the 12-h time point. However, no obvious differences were
      found at the 24-h time point. This study demonstrated that the HBO treatment can
      promote the apoptosis of PBLs via a mitochondrial-dependent pathway and inhibit
      the inflammatory response. These immunoregulatory effects may play an important
      therapeutic role in attenuating the severity of early stage AP. The repeated
      administration of HBO or the use of HBO in combination with other approaches may
      further improve outcomes.

PMID- 24101213
TI  - Predictors of disapproval toward "hard drug" use among high school seniors in the
      US.
AB  - Attitudes toward drug use strongly determine whether an individual initiates use.
      Personal disapproval toward the use of a particular drug is strongly protective
      against use; however, little is known regarding how the use of one drug affects
      attitudes toward the use of other drugs. Since marijuana use is on the rise in
      the US and disapproval toward use is decreasing, research is needed to determine
      whether the use of marijuana or other licit or illicit drugs reduces disapproval
      toward the use of "harder," more potentially dangerous drugs. The Monitoring the
      Future study assesses a national representative sample of high school seniors in
      the US each year. This study investigated predictors of disapproval toward the
      use of powder cocaine, crack, lysergic acid diethylamide (LSD), heroin,
      amphetamine, and ecstasy ("Molly") in a weighted sample of 29,054 students from
      five cohorts (2007-2011). Results suggest that lifetime use of cigarettes and use
      of more than one hard drug consistently lowered odds of disapproval. In
      multivariable models, lifetime alcohol use did not affect odds of disapproval and
      lifetime marijuana use (without the use of any "harder" drugs) lowered odds of
      disapproval of LSD, amphetamine, and ecstasy, but not cocaine, crack, or heroin.
      In conclusion, marijuana use within itself is not a consistent risk factor for
      lower disapproval toward the use of harder drugs. Cigarette and hard drug use,
      however, are more consistent risk factors. As marijuana prevalence increases and
      policy becomes more lenient toward recreational and medicinal use, public health
      and policy experts need to ensure that attitudinal-related risk does not increase
      for the use of other drugs. 

PMID- 24101214
TI  - Segmental and restricted localization pattern of Fras1 in the developing
      meningeal basement membrane in mouse.
AB  - The Fras1/Frem family of extracellular matrix proteins consists of Fras1 and its
      structurally related proteins, Frem1 (Fras1-related extracellular matrix protein
      1), Frem2 and Frem3. These are co-localized in embryonic epithelial basement
      membranes (BMs), where they contribute to epithelial-mesenchymal adhesion.
      Although Fras1 localization pattern in epithelial BMs has been well defined, it
      has not yet been comprehensively studied in the central nervous system. Here, we
      demonstrate the immunohistochemical profile of Fras1 in the developing mouse
      brain and reveal an exclusively meningeal BM protein deposition. Interestingly,
      Fras1 displays a segmental localization pattern, which is restricted to certain
      regions of the meningeal BM. Frem2 protein displays a similar localization
      pattern, while Frem3 is rather uniformly distributed throughout the meningeal BM.
      Fras1 and Frem2 proteins are detected in regions of the BM that underlie
      organizing centers, such as the roof plate (RP) of diencephalon, midbrain and
      hindbrain, and the RP-derived structures of telencephalon (choroid plexus and
      hem). Organizing centers exert their activity via the production of bioactive
      molecules, which are potential Fras1 ligands. The restricted pattern of Fras1 and
      Frem2 proteins indicates a molecular compartmentalization of the meningeal BM
      that could reflect, yet unspecified, functional and structural differences. 

PMID- 24101215
TI  - Evaluating the 21-gene assay Recurrence Score(r) as a predictor of clinical
      response to 24 weeks of neoadjuvant exemestane in estrogen receptor-positive
      breast cancer.
AB  - BACKGROUND: The aim of this study was to investigate the association between the
      results of the Recurrence Score (RS) assay and the clinical response to
      neoadjuvant endocrine therapy in postmenopausal women with breast cancer.
      METHODS: Core biopsy samples at baseline and post-treatment surgical samples were
      obtained from 80 and 77 of 116 patients, respectively, enrolled in the
      multicenter prospective study of neoadjuvant exemestane therapy (JFMC34-0601).
      The 21-gene assay was performed after appropriate manual microdissection. The
      estrogen receptor (ER), progesterone receptor, HER2 and Ki-67 were assayed by
      immunohistochemistry at a central laboratory. Clinical response was assessed
      based on the RECIST (Response Evaluation Criteria In Solid Tumors) guideline.
      RESULTS: Sixty-four core biopsy samples and 52 resection samples met the RS
      quality requirements. The clinical response rate in those patients with a low RS
      result (low RS group; 19/32, 59.4 %) was significantly higher than that in those
      patients with a high RS result (high RS group; 3/15, 20.0 %) (P = 0.015) and
      similar to that in patients with an intermediate RS result (intermediate RS
      group; 10/17, 58.8 %). The rates of breast-conserving surgery (BCS) were 90.6 %
      (29/32) in the low RS group, 76.5 % (13/17) in the intermediate RS group and 46.7
      % (7/15) in the high RS group. The odds ratio for BCS adjusted for continuous
      baseline Ki-67 was 0.114 [95 % confidence interval (CI) 0.014-0.721; P = 0.028]
      between the high and low RS groups. RS values in pre-treatment samples were
      highly correlated with those in post-treatment samples (Spearman correlation
      coefficient 0.745, 95 % CI 0.592-0.846). CONCLUSION: Our results demonstrate the
      predictive value of the RS for clinical response to neoadjuvant exemestane
      therapy in postmenopausal women with ER-positive breast cancer.

PMID- 24101219
TI  - Diminished ovarian reserve. How do you diagnosis it? What does it mean?

PMID- 24101216
TI  - Partial portal vein arterialization in acute liver failure.
AB  - Experimental studies have shown that increasing the oxygen supply to the liver
      through partial portal vein arterialization (PPVA) enhances liver regeneration
      after extensive liver resection or drug intoxication. In the last two decades,
      several PPVA procedures were performed in humans with the aim to prevent or treat
      acute liver failure (ALF) following major hepatobiliary surgery or other
      etiology. The aim of this review was to analyze literature data on PPVA and
      report our experimental and clinical experience of this procedure. In this
      setting, we report our positive experience in the realization and clinical
      application of an extracorporeal device able to increase the oxygenated blood
      delivered to the liver through the umbilical vein and to support liver function
      in a man subjected to an extended liver resection. PPVA procedure has shown
      promising results in the treatment of ALF following major hepatobiliary surgery
      or from other etiology. Moreover, less invasive approaches to PPVA demonstrated
      to be safe and efficacy. It is clear that further investigations must be done to
      fully understand the potentiality of PPVA as a strategy to treat ALF. 

PMID- 24101220
TI  - Oocyte development and loss.
AB  - Soon after implantation, cell lineages bifurcate into future somatic and germ
      cells. Canonical expression of germ cell-specific genes continues during and
      after their migration to the gonadal ridge, where, after further cell cycles,
      they enter meiosis, form syncytial clusters, and arrest at diplotene for
      folliculogenesis. The balance between cell survival and death leaves an ovarian
      follicular reserve as a legacy. 

PMID- 24101222
TI  - Predicting reproductive age with biomarkers of ovarian reserve--how (and what)
      are we measuring?
AB  - Predicting the reproductive lifespan of an individual woman remains an elusive,
      yet clinically important, goal. The development of models and staging systems
      that accurately determine the end of natural fertility and the anticipated age of
      menopause will represent a significant advance in our ability to counsel women
      regarding family planning issues and in the individualization of risk assessment.
      Recent histological and longitudinal investigations have demonstrated a
      significant relationship between commonly used clinical markers of ovarian
      reserve and the true ovarian reserve, as assessed by the ovarian nongrowing
      follicle count and the age of menopause, respectively. Models and staging systems
      that have been developed based on these findings represent important advances in
      the field of women's health and promise to provide additional insights into the
      process of reproductive aging in general. Although the models developed to date
      appear to improve the prediction of the age of menopause as compared with
      chronological age alone, wide confidence intervals in the predicted age of
      menopause and less accurate predictions at ages remote from menopause limit their
      clinical utility for the individual woman. Future longitudinal and histological
      investigations are necessary to improve the accuracy of models of reproductive
      aging. 

PMID- 24101223
TI  - What is normal ovarian reserve?
AB  - While hormonal and ultrasonographic measures of ovarian reserve are often used to
      counsel patients about their fertility potential, normative data for these
      markers in the general population are lacking. Most studies are cross sectional
      and take place within specific subpopulations. Antral follicle count and anti
      Mullerian hormone have been shown to be the best indicators of a woman's total
      follicular reserve. Ovarian volume, inhibin B, estradiol, and follicle
      stimulating hormone are less helpful. Antral follicle count and anti-Mullerian
      hormone decrease with age and have been used to attempt to predict the length of
      the fertile window. Additional longitudinal data are needed for these biomarkers
      in populations of young, healthy, multiethnic women to assess for the presence of
      cofactors and determine the rate of age-related decline. Currently, these
      biomarkers are insufficient as predictors of fertility potential or advancement
      to menopause and no definitive determinations can be made about what constitutes
      "normal" levels of each measure. 

PMID- 24101224
TI  - Biomarkers of ovarian reserve as predictors of reproductive potential.
AB  - The size of the oocyte pool, the ovarian reserve, can determine a woman's
      reproductive stage. Chronologic age, anti-Mullerian hormone (AMH) levels, early
      follicular phase follicle-stimulating hormone levels, and early follicular phase
      inhibin B levels are correlated with ovarian reserve. Therefore, these biomarkers
      of ovarian reserve should serve as predictors of reproductive potential. Clinical
      and epidemiologic studies suggest that historical and laboratory biomarkers of
      ovarian reserve are associated with natural and treatment-related fertility.
      However, controversy remains as to their ability to predict reproductive
      potential. For infertile women undergoing assisted reproductive technology
      treatment, these biomarkers tend to be highly specific but not sensitive for
      cycle failure (nonpregnancy). While these biomarkers are being used as "fertility
      tests" in the general population, their value as predictors of unassisted
      fertility is still uncertain. Among laboratory biomarkers, AMH appears to have
      the most promise; however, further studies are needed to refine cutoff values and
      to determine test characteristics in the prediction of natural fertility or
      infertility in the general population. 

PMID- 24101221
TI  - Genomic markers of ovarian reserve.
AB  - Ovarian reserve and its utilization, over a reproductive life span, are
      determined by genetic, epigenetic, and environmental factors. The establishment
      of the primordial follicle pool and the rate of primordial follicle activation
      have been under intense study to determine genetic factors that affect
      reproductive lifespan. Much has been learned from transgenic animal models about
      the developmental origins of the primordial follicle pool and mechanisms that
      lead to primordial follicle activation, folliculogenesis, and the maturation of a
      single oocyte with each menstrual cycle. Recent genome-wide association studies
      on the age of human menopause have identified approximately 20 loci, and shown
      the importance of factors involved in double-strand break repair and immunology.
      Studies to date from animal models and humans show that many genes determine
      ovarian aging, and that there is no single dominant allele yet responsible for
      depletion of the ovarian reserve. Personalized genomic approaches will need to
      take into account the high degree of genetic heterogeneity, family pedigree, and
      functional data of the genes critical at various stages of ovarian development to
      predict women's reproductive life span. 

PMID- 24101225
TI  - Biomarkers of ovarian reserve--do they predict somatic aging?
AB  - Menopause, while the end of reproduction, also represents a major hormonal,
      psychological and physiological event in the lives of all women. Several studies
      have suggested an association between the age of menopause and longevity.
      Additionally, cellular and molecular mechanisms of general aging have been
      suggested to play a vital role in ovarian aging. In parallel with the recognition
      of these similar physiological parameters, markers of "ovarian age," also known
      as ovarian reserve, have been developed. These markers may allow prediction of
      age of menopause and the identification of women at increased risk for earlier
      menopause, and perhaps advanced somatic aging. The ability to identify these
      women would be critically important if decreased ovarian reserve were associated
      with increased long-term health risks. Thus, it is critical to understand if
      ovarian aging, and particularly, early ovarian aging, would place women at risk
      for long-term health issues with increased morbidity and mortality. Numerous
      studies reviewed support an association between menopause, and premenopausal
      changes consistent with diminish ovarian reserve, and cardiovascular risk, bone
      loss and changes in mood and cognition. Only longitudinal studies will be able to
      confirm if any identified associations reflect causality or common underlying
      risk, but the available data suggest women with diminished ovarian reserve
      represent a unique group that may be at increased risk for long-term health
      effects beyond fertility loss. 

PMID- 24101226
TI  - Biomarkers of ovarian reserve in women with polycystic ovary syndrome.
AB  - Recent years have seen an acceleration of research on biomarkers of ovarian
      reserve, with most inquiries targeted toward what these markers tell us about
      fertility and the reproductive lifespan. However, in the patient with polycystic
      ovarian syndrome (PCOS), ovarian reserve markers may provide information about
      the condition itself. This review will consider the use of common markers of
      functional ovarian reserve, including antral follicle count, ovarian volume, and
      anti-Mullerian hormone in the PCOS population for the purposes of diagnosing
      PCOS, characterizing the PCOS phenotype, and predicting response to fertility
      treatment. 

PMID- 24101227
TI  - Accelerating ovarian age: cancer treatment in the premenopausal woman.
AB  - The reproductive sequelae of cancer treatments may provide an important model of
      accelerated ovarian aging. Tens of thousands of women treated for cancer each
      year experience infertility and early menopause as a result of treatment. A
      spectrum of reproductive compromise commonly ranges from immediate menopause at
      the time of cancer treatment to the less proximate outcome of early menopause in
      the years to decades after treatment. A woman's reproductive lifespan can be
      shortened after chemotherapy or radiation because such treatments likely decrease
      the number of viable eggs after treatment. This acceleration in the decline of
      the number of follicles leads to increased rates of not only infertility and
      miscarriage but also early menopause, which represents the most extreme form of
      accelerated ovarian aging. The degree of reproductive impairment is dependent on
      chronologic age and the diagnosis or treatment. The variation in outcomes that
      persist may be partially explained by pretreatment ovarian reserve. Establishing
      the use of clinical predictors such as ovarian reserve markers to effectively
      anticipate such outcomes is an obvious and important keystone in the foundation
      of cancer survivorship research. An improved understanding of cancer treatment's
      ability to accelerate follicle death, decrease fecundability, and initiate an
      earlier menopause could provide a clinically relevant, time-shortened, and
      reproducible snapshot into the basic biology of ovarian aging. 

PMID- 24101228
TI  - APG350 induces superior clustering of TRAIL receptors and shows therapeutic
      antitumor efficacy independent of cross-linking via Fcgamma receptors.
AB  - Cancer cells can be specifically driven into apoptosis by activating Death
      receptor-4 (DR4; TRAIL-R1) and/or Death-receptor-5 (DR5; TRAIL-R2). Albeit
      showing promising preclinical efficacy, first-generation protein therapeutics
      addressing this pathway, especially agonistic anti-DR4/DR5-monoclonal antibodies,
      have not been clinically successful to date. Due to their bivalent binding mode,
      effective apoptosis induction by agonistic TRAIL-R antibodies is achieved only
      upon additional events leading to antibody-multimer formation. The binding of
      these multimers to their target subsequently leads to effective receptor
      clustering on cancer cells. The research results presented here report on a new
      class of TRAIL-receptor agonists overcoming this intrinsic limitation observed
      for antibodies in general. The main feature of these agonists is a TRAIL-mimic
      consisting of three TRAIL-protomer subsequences combined in one polypeptide
      chain, termed the single-chain TRAIL-receptor-binding domain (scTRAIL-RBD). In
      the active compounds, two scTRAIL-RBDs with three receptor binding sites each are
      brought molecularly in close proximity resulting in a fusion protein with a
      hexavalent binding mode. In the case of APG350-the prototype of this engineering
      concept-this is achieved by fusing the Fc-part of a human immunoglobulin G1
      (IgG1)-mutein C-terminally to the scTRAIL-RBD polypeptide, thereby creating six
      receptor binding sites per drug molecule. In vitro, APG350 is a potent inducer of
      apoptosis on human tumor cell lines and primary tumor cells. In vivo, treatment
      of mice bearing Colo205-xenograft tumors with APG350 showed a dose-dependent
      antitumor efficacy. By dedicated muteins, we confirmed that the observed in vivo
      efficacy of the hexavalent scTRAIL-RBD fusion proteins is-in contrast to
      agonistic antibodies-independent of FcgammaR-based cross-linking events.

PMID- 24101229
TI  - Hip fracture risk and cadmium in erythrocytes: a nested case-control study with
      prospectively collected samples.
AB  - Several studies have investigated the relation between bone mass density and
      cadmium exposure, but only few studies have been performed on fractures and
      biomarkers of cadmium. This study analyzed the association between hip fracture
      risk and cadmium in erythrocytes (Ery-Cd). Prospective samples from the Northern
      Sweden Health and Disease Study's biobank were used for 109 individuals who later
      in life had sustained a low-trauma hip fracture, matched with two controls of the
      same age and gender. The mean concentration of Ery-Cd (+/-SD) in case samples was
      1.3 +/- 1.4 versus 0.9 +/- 1.0 MUg/L in controls. The odds ratio (OR) was 1.63
      [95% confidence interval (CI) 1.10-2.42] for suffering a hip fracture for each
      microgram per liter increase in Ery-Cd. However, when taking smoking into
      consideration (never, former, or current), neither Ery-Cd nor smoking showed a
      statistically significant increase in fracture risk. Using multiple conditional
      logistic regression with BMI, height, and smoking, the estimated OR for a 1-MUg/L
      increase in Ery-Cd was 1.52 (95% CI 0.77-2.97). Subgroup analysis showed an
      increased fracture risk among women (OR = 1.94, 95% CI 1.18-3.20, for a 1 MUg/L
      increase), which also remained in the multiple analysis (OR = 3.33, 95% CI 1.29
      8.56). This study shows that fracture risk is associated with Ery-Cd. It is,
      however, not possible to draw firm conclusions on whether cadmium is the causal
      factor or whether other smoking-related factors cause this association. Subgroup
      analysis shows that cadmium is a risk factor for hip fracture among women.

PMID- 24101230
TI  - A pediatric bone mass scan has poor ability to predict adult bone mass: a 28-year
      prospective study in 214 children.
AB  - As the correlation of bone mass from childhood to adulthood is unclear, we
      conducted a long-term prospective observational study to determine if a pediatric
      bone mass scan could predict adult bone mass. We measured cortical bone mineral
      content (BMC [g]), bone mineral density (BMD [g/cm(2)]), and bone width (cm) in
      the distal forearm by single photon absorptiometry in 120 boys and 94 girls with
      a mean age of 10 years (range 3-17) and mean 28 years (range 25-29) later. We
      calculated individual and age-specific bone mass Z scores, using the control
      cohort included at baseline as reference, and evaluated correlations between the
      two measurements with Pearson's correlation coefficient. Individual Z scores were
      also stratified in quartiles to register movements between quartiles from growth
      to adulthood. BMD Z scores in childhood and adulthood correlated in both boys (r
      = 0.35, p < 0.0001) and girls (r = 0.50, p < 0.0001) and in both children >=10
      years at baseline (boys r = 0.43 and girls r = 0.58, both p < 0.0001) and
      children <10 years at baseline (boys r = 0.26 and girls r = 0.40, both p < 0.05).
      Of the children in the lowest quartile of BMD, 58% had left the lowest quartile
      in adulthood. A pediatric bone scan with a value in the lowest quartile had a
      sensitivity of 48% (95% confidence interval [CI] 27-69%) and a specificity of 76%
      (95% CI 66-84%) to identify individuals who would remain in the lowest quartile
      also in adulthood. Childhood forearm BMD explained 12% of the variance in adult
      BMD in men and 25% in women. A pediatric distal forearm BMD scan has poor ability
      to predict adult bone mass.

PMID- 24101232
TI  - Strontium localization in bone tissue studied by X-ray absorption spectroscopy.
AB  - Strontium has recently been introduced as a pharmacological agent for the
      treatment and prevention of osteoporosis. We determined the localization of
      strontium incorporated into bone matrix from dogs treated with Sr malonate by X
      ray absorption spectroscopy. A new approach for analyzing the X-ray absorption
      spectra resulted in a compositional model and allowed the relative distribution
      of strontium in the different bone components to be estimated. Approximately 35
      45% of the strontium present is incorporated into calcium hydroxyapatite (CaHA)
      by substitution of some of the calcium ions occupying highly ordered sites, and
      at least 30% is located at less ordered sites where only the first solvation
      shell is resolved, suggesting that strontium is surrounded by only oxygen atoms
      similar to Sr(2+) in solution. Strontium was furthermore shown to be absorbed in
      collagen in which it obtains a higher structural order than when present in serum
      but less order than when it is incorporated into CaHA. The total amount of
      strontium in the samples was determined by inductively coupled plasma mass
      spectrometry, and the amount of Sr was found to increase with increasing dose
      levels and treatment periods, whereas the relative distribution of strontium
      among the different components appears to be independent of treatment period and
      dose level.

PMID- 24101233
TI  - Adipocytes and the regulation of bone remodeling: a balancing act.
AB  - Throughout life, a balance exists within the marrow cavity between adipose tissue
      and bone. Each tissue derives from a common progenitor cell known both as a "bone
      marrow-derived multipotent stromal cell" and as a "mesenchymal stem cell" (BMSC).
      The majority of in vitro and in vivo data suggest that BMSCs differentiate into
      adipocytes or osteoblasts in a reciprocal manner. For example, while ligand
      induction of the transcription factors peroxisome proliferator-activated receptor
      gamma initiates BMSC adipogenesis, it suppresses osteogenesis. Nevertheless, this
      hypothesis may oversimplify a complex regulatory paradigm. The picture may be
      further complicated by the systemic impact of extramedullary adipose depots on
      bone via the secretion of protein adipokines and lipid metabolites. This review
      focuses on past and current literature examining the mechanisms governing the
      adipose-bone interface. 

PMID- 24101231
TI  - Cellular complexity of the bone marrow hematopoietic stem cell niche.
AB  - The skeleton serves as the principal site for hematopoiesis in adult terrestrial
      vertebrates. The function of the hematopoietic system is to maintain homeostatic
      levels of all circulating blood cells, including myeloid cells, lymphoid cells,
      red blood cells, and platelets. This action requires the daily production of more
      than 500 billion blood cells. The vast majority of these cells are synthesized in
      the bone marrow, where they arise from a limited number of hematopoietic stem
      cells (HSCs) that are multipotent and capable of extensive self-renewal. These
      attributes of HSCs are best demonstrated by marrow transplantation, where even a
      single HSC can repopulate the entire hematopoietic system. HSCs are therefore
      adult stem cells capable of multilineage repopulation, poised between cell fate
      choices which include quiescence, self-renewal, differentiation, and apoptosis.
      While HSC fate choices are in part determined by multiple stochastic fluctuations
      of cell autonomous processes, according to the niche hypothesis, signals from the
      microenvironment are also likely to determine stem cell fate. While it had long
      been postulated that signals within the bone marrow could provide regulation of
      hematopoietic cells, it is only in the past decade that advances in flow
      cytometry and genetic models have allowed for a deeper understanding of the
      microenvironmental regulation of HSCs. In this review, we will highlight the
      cellular regulatory components of the HSC niche. 

PMID- 24101234
TI  - Personality as continuous stochastic process: what Western personality theory can
      learn from classical confucianism.
AB  - An important objective of personality psychology is to provide compelling
      descriptions and explanations of intraindividual personality dynamics that
      capture the unique qualities of persons. Among contemporary Western personality
      theories, the Five-Factor Model enjoys prominence in describing individual
      differences in personality traits. It falls short, however, in its ability to
      work with intraindividual personality function. This article argues that
      classical Confucianism, originating 2500 years ago in mainland China, offers
      Western personality psychologists important theoretical resources for capturing
      the complex and dynamic processes inherent in human personality. The Confucian
      perspective emphasizes a behaviorally anchored, continuous, stochastic, process
      oriented understanding of the self as relationally constructed and proposes an
      elegant description of the relational virtuosity of exemplary persons. The
      article concludes with five characteristics of a Confucian inspired model of
      personality and questions the viability of a universal theory of personality.

PMID- 24101235
TI  - A "rendezvous technique" for treating a pancreatic fistula after distal
      pancreatectomy.
AB  - BACKGROUND: Pancreatic fistulae are a major complication of distal pancreatectomy
      (DP). Some cases of severe pancreatic fistula require invasive procedures. There
      have been some reports concerning the effectiveness of pancreatic duct drainage
      through an endoscopic transpapillary approach for pancreatic fistulae. CASE
      PRESENTATION: We herein present a case of a pancreatic fistula after DP that was
      successfully treated with percutaneous pancreatic duct drainage, which was
      performed using a combined percutaneous and endoscopic approach, named the
      "rendezvous technique". In our case, we performed distal pancreatectomy with
      celiac artery resection for a locally advanced pancreatic body cancer. On
      postoperative day (POD) 7, the drain amylase level increased up to 37,460 IU/l.
      Computed tomography (CT) revealed peripancreatic fluid collections. On POD 10, we
      placed a catheter in the main pancreatic duct using the rendezvous technique. CT
      on POD 14 revealed a decrease in the size of the peripancreatic fluid collection,
      and contrast imaging from the drains on POD 22 revealed almost complete
      disappearance of the fluid collection. We withdrew the pigtail catheter on POD 27
      and the percutaneous pancreatic duct drain on POD 36. This patient was discharged
      from our hospital on POD 40. CONCLUSION: We herein report a new approach called
      the "rendezvous technique" for the management of pancreatic fistulae after DP
      that can be used instead of a stressful nasopancreatic tube.

PMID- 24101237
TI  - Painful paediatric hip: frog-leg lateral view only!
AB  - OBJECTIVE: For hip complaints in the paediatric population, it is common practice
      to acquire both anteroposterior (AP) and frog-leg lateral (FL) radiographs. This
      combination of views provides a high diagnostic yield, but also doubles radiation
      exposure. We investigated the diagnostic accuracy of obtaining a solitary FL view
      as compared to a combination of the AP and FL view. METHODS: Hip radiographs of
      524 children (aged 2-15 years) referred for acute hip pain were retrospectively
      assessed by two independent radiologists. Cases of trauma, neuromuscular
      disorders or a history of known hip disease were excluded. Radiologists were
      blinded to the AP radiograph while assessing the solitary FL radiograph. We used
      Cohen's kappa test to calculate agreement between the assessment of both views
      and the solitary FL view. RESULTS: Agreement between the assessment of the
      solitary FL view and the combination of the AP and FL view was very high with a
      kappa value of 0.989. CONCLUSION: The diagnostic accuracy of the FL radiograph in
      cases of hip complaints in children is as high as the current standard employing
      both AP and FL views. Therefore a solitary FL radiograph appears sufficient. This
      practice would substantially reduce radiation exposure. KEY POINTS: * Radiation
      exposure in children should be kept to a minimum. * In paediatric hip radiography
      a solitary frog-leg lateral view suffices. * This reduces radiation exposure and
      costs of imaging.

PMID- 24101236
TI  - Contrast-enhanced MRI compared with the physical examination in the evaluation of
      disease activity in juvenile idiopathic arthritis.
AB  - OBJECTIVES: To assess the value of magnetic resonance imaging (MRI) in
      discriminating between active and inactive juvenile idiopathic arthritis (JIA)
      patients and to compare physical examination outcomes with MRI outcomes in the
      assessment of disease status in JIA patients. METHODS: Consecutive JIA patients
      with knee involvement were prospectively studied using an open-bore MRI. Imaging
      findings from 146 JIA patients were analysed (59.6% female; mean age, 12.9
      years). Patients were classified as clinically active or inactive. MRI features
      were evaluated using the JAMRIS system, comprising validated scores for synovial
      hypertrophy, bone marrow oedema, cartilage lesions and bone erosions. RESULTS:
      Inter-reader reliability was good for all MRI features (intra-class correlation
      coefficient [ICC] = 0.87-0.94). No differences were found between the two groups
      regarding MRI scores of bone marrow oedema, cartilage lesions or bone erosions.
      Synovial hypertrophy scores differed significantly between groups (P = 0.016).
      Nonetheless, synovial hypertrophy was also present in 14 JIA patients (35.9%)
      with clinically inactive disease. Of JIA patients considered clinically active,
      48.6% showed no signs of MRI-based synovitis. CONCLUSIONS: MRI can discriminate
      between clinically active and inactive JIA patients. However, physical
      examination is neither very sensitive nor specific in evaluating JIA disease
      activity compared with MRI. Subclinical synovitis was present in >35% of presumed
      clinically inactive patients. KEY POINTS: * MRI is sensitive for evaluating
      juvenile idiopathic arthritis (JIA) disease activity. * Contrast-enhanced MRI can
      distinguish clinically active and inactive JIA patients. * Subclinical synovitis
      is present in 35.9 % of presumed clinically inactive patients. * Physical
      examination is neither sensitive nor specific in evaluating JIA disease activity.

PMID- 24101238
TI  - A rapid and cost-effective method of producing recombinant proBNP and NT-proBNP
      variants in Escherichia coli for immunoassay of heart failure.
AB  - The measurements of plasma natriuretic peptides (NT-proBNP, proBNP and BNP) are
      used to diagnose heart failure but these are expensive to produce. We describe a
      rapid, cheap and facile production of proteins for immunoassays of heart failure.
      DNA encoding N-terminally His-tagged NT-proBNP and proBNP were cloned into the
      pJexpress404 vector. ProBNP and NT-proBNP peptides were expressed in Escherichia
      coli, purified and refolded in vitro. The analytical performance of these
      peptides were comparable with commercial analytes (NT-proBNP EC50 for the
      recombinant is 2.6 ng/ml and for the commercial material is 5.3 ng/ml) and the
      EC50 for recombinant and commercial proBNP, are 3.6 and 5.7 ng/ml respectively).
      Total yield of purified refolded NT-proBNP peptide was 1.75 mg/l and proBNP was
      0.088 mg/l. This approach may also be useful in expressing other protein analytes
      for immunoassay applications. PURPOSE OF WORK: To develop a cost effective
      protein expression method in E. coli to obtain high yields of NT-proBNP (1.75
      mg/l) and proBNP (0.088 mg/l) peptides for immunoassay use.

PMID- 24101239
TI  - Molecular cloning and expression of a novel laccase showing thermo- and acid
      stability from the endophytic fungus Phomopsis liquidambari and its potential for
      growth promotion of plants.
AB  - A novel laccase (LACB3) from the endophytic fungus, Phomopsis liquidambari, was
      cloned and its potential to promote peanut growth was evaluated. The full-length
      cDNA is 1,731 bp, encoding a mature protein of 556 amino acids with a molecular
      mass of 60.1 kDa. Using 2,2'-azino-bis(3-ethylbenzthiazoline-6-sulfonate), LACB3
      exhibited a K m and k cat of 85 MUM and 92.7 s(-1), respectively. The enzyme had
      maximal activity at pH 2.5 and 50  degrees C and retained 50 % of its activity
      after 20 h at 50  degrees C. When LACB3 was applied to soil, the peanut biomass
      was increased by 12 %, and the content of vanillic acid, coumaric acid and 4
      hydroxybenzoic acid in soil were decreased by 21, 27 and 40 %, respectively.
      These results suggest substantial potential for the use of P. liquidambari or its
      laccase in agriculture. 

PMID- 24101240
TI  - Improved cellobiose utilization in E. coli by including both hydrolysis and
      phosphorolysis mechanisms.
AB  - Cellobiose is a major intermediate from cellulase hydrolysis of pretreated plant
      biomass. Engineering biocatalysts for direct use of cellobiose could eliminate
      the need for exogenous beta-glucosidase. Additionally, rapid removal of
      cellobiose in a simultaneous saccharification and fermentation facilitates
      enzymatic hydrolysis as cellobiose is a potent inhibitor for cellulases. We
      report here improved cellobiose utilization by engineering Escherichia coli to
      assimilate the disaccharide both hydrolytically and phosphorolytically (shorter
      fermentation time). Additionally, we demonstrate that engineering intracellular
      cellobiose utilization circumvents catabolite repression allowing simultaneous
      fermentation of xylose and cellobiose. Using meso-2,3-butanediol as model
      product, we further demonstrate that the accelerated carbon metabolism led to
      improved product formation (higher titers and shorter fermentation times),
      illustrating the utility of the engineered biocatalysts in biorefinery
      applications. 

PMID- 24101241
TI  - Transgene-induced pleiotropic effects in transplastomic plants.
AB  - Since the first demonstration of stable transgene integration in the plastid
      genome (plastome) of higher plants, plastid transformation has been used for a
      wide range of purposes, including basic studies as well as biotechnological
      applications, showing that transplastomic plants are an effective system to
      produce recombinant proteins. Compared to nuclear transformation, the main
      advantages of this technology are the high and stable production level of
      proteins as well as the natural containment of transgenes. To date, more than 100
      transgenes have been successfully expressed in plant chloroplasts. In some cases,
      however, unintended pleiotropic effects on plant growth and physiology were shown
      in transplastomic plants. In this paper, we review such effects and discuss some
      of the technologies developed to overcome them. 

PMID- 24101242
TI  - Alanine-scanning mutation approach for classification of the roles of conserved
      residues in the activity and substrate affinity of L-carnitine dehydrogenase.
AB  - L-Carnitine dehydrogenase (CDH) is as an excellent tool for L-carnitine (L-Car)
      estimation. To date, four CDHs have been identified, that share 45 % homology of
      their proteins. Here 42 conserved residues of CDH from Xanthomonas translucens
      (Xt-CDH) were substituted successively with alanine. The resultant mutants were
      analyzed for catalytic activity. Active mutants were evaluated for their
      influence on L-Car affinity. Twenty-three mutants with reduced affinity toward L
      Car were subjected to detailed kinetic analysis. Analytical data implied that all
      mutants had increased K m values. The mutants of R193A, E196A, W199A, R200A,
      F249A, and F253A that produced the greatest L-Car affinity disruption (K m > 200
      folds of Xt-CDH) clustered near the putative active site. This information can
      provide a solid basis for the rational design of mutagenic investigation to
      improve CDHs. 

PMID- 24101243
TI  - Four novel antimicrobial peptides derived from human C8alpha-MACPF.
AB  - Antimicrobial peptides are active against a diverse spectrum of microorganisms.
      Using a bioinformatics method, six potential novel antimicrobial peptides, A1,
      C1, A2, A3, C2 and A4, were identified in the C8alpha complement component. The
      corresponding genes were then cloned into a new vector as fusions with the self
      cleavage protein N(pro) protein mutant EDDIE gene. The expressed or synthetic
      peptides, A1, A2, A3 and A4, showed antimicrobial activities against several
      bacteria, while peptides C1 and C2 did not. Peptides A1 to A4 showed no hemolytic
      activities over 3 h when at 500 MUg/ml. Thus, A1, A2, A3 and A4, derived from the
      C8alpha complement system, are novel antimicrobial peptides. 

PMID- 24101244
TI  - Surface-functionalized gold nanoparticles mediate bacterial transformation: a
      nanobiotechnological approach.
AB  - Transformation of bacteria is an important step in molecular biology. Viral and
      non-virus-based gene delivery techniques, including chemical/biological and
      physical approaches, have been applied to bacterial, mammalian and plant cells.
      E. coli is not competent to take up DNA; hence, different methods are used to
      incorporate plasmid DNA. A novel method has been developed using glutathione
      functionalized gold nanoparticles to mediate transformation of plasmid DNA
      (pUC19) into E. coli DH5alpha that does not require the preparation of competent
      cells. The glutathione-functionalized gold nanoparticles acted as a vector and
      facilitated the entry of DNA into the host cell. The method also gave a higher
      transformation efficiency (4.2 * 10(7)/MUg DNA) compared to 2.3 * 10(5)/MUg DNA
      using the conventional CaCl2-mediated method. It was also non-toxic to the
      bacterium making it suitable for biotechnological applications. 

PMID- 24101245
TI  - Occurrence and reactivation of viable but non-culturable E. coli in sewage sludge
      after mesophilic and thermophilic anaerobic digestion.
AB  - The occurrence and reactivation of viable but non-culturable (VBNC) Escherichia
      coli after different anaerobic digestions and the subsequent dewatering and
      storage were evaluated and compared. Culturable E. coli in digested sludge
      increased by two to four orders of magnitudes immediately after dewatering.
      However, counts of both the total and viable E. coli indicated that the increase
      of E. coli was attributed to its reactivation from the VBNC state to the
      culturable state. The VBNC pathogen incidences of thermophilic digestion were two
      to three orders of magnitude higher than those of mesophilic digestion.
      Accordingly, culturable E. coli in thermophilic, digested sludge after storage
      were one order of magnitude higher than mesophilic digestion. Anaerobic digestion
      thus mainly alters the culturable state of pathogens rather than killing them;
      therefore the biological safety of digested sludge, especially temperature-phased
      anaerobic digestion, should be carefully assessed. 

PMID- 24101246
TI  - Genetic engineering techniques for lactic acid bacteria: construction of a stable
      shuttle vector and expression vector for beta-glucuronidase.
AB  - The shuttle vector, pUL6erm, was constructed by using a replicon from pL2, a
      multiple cloning site, colE1 ori, the ori of Gram-negative bacteria from vector
      pUC19, and the erythromycin resistance gene from pVA838 as a selection marker.
      pUL6erm could be transformed easily and maintained stably in Lactococcus lactis,
      Streptococcus thermophilus, Lactobacillus plantarum and Lactobacillus casei.
      Transformation assays of pUL6erm indicated that it had a narrow host range. beta
      Glucuronidase was induced in the presence of 0.3 M NaCl and 50 mM glutamate and
      expressed at 2.4 U mg(-1) with the expression vector (pUL6erm-gadR-GUS)
      constructed based on pUL6erm carrying beta-glucuronidase gene wuth a chloride
      inducible (gadR) expression cassette using Pgad as promoter. Therefore, pUL6erm
      and pUL6erm-gadR-GUS might be a safe and useful genetic tool for the improvement
      of lactic acid bacteria. 

PMID- 24101247
TI  - Genomic DNAs in a human leukemia cell line unfold after cold shock, with
      formation of neutrophil extracellular trap-like structures.
AB  - Cells are generally stored at low temperature which slows their cellular
      metabolism. However, the stress induced by cold shock can lead to cell injury or
      death. Here, we found that exposing human leukemia HL-60 cells to cold shock
      followed by rewarming (CS/RW) increased the number of dead cells with remodeled
      genomic structures in which DNA fibers fully unfold and extrude into
      extracellular space, similar to neutrophil extracellular traps (NETs). The
      unfolded DNA was associated with NET marker proteins, such as neutrophil elastase
      and histone H3, and could trap significant numbers of Escherichia coli. We also
      found that reactive oxygen species-a requisite for NET generation-accumulated
      during CS/RW in HL-60 cells. This treatment of HL-60 cells to trigger global DNA
      structural alterations has not been reported before, and helps to elucidate the
      mechanisms of human cellular response to cold stress. 

PMID- 24101248
TI  - A fast and simple approach to the quantitative evaluation of fibrinogen
      coagulation.
AB  - Fibrinogen is essential in the intrinsic and extrinsic blood coagulation process.
      Inhibition of fibrinogen aggregation could lead to anticoagulation effects. The
      availability of methods for easy quantitative evaluation of the coagulation
      process is critical to studying coagulation and its inhibition. A commonly used
      method is UV-Vis absorbance (405 nm) detection by a micro-plate reader. However,
      because of the heterogeneous nature of the resulting mixture in a coagulation
      process, transmission-based optical measurements give large variations. Herein, a
      very simple and easy method is developed for the quantitative measurements of the
      coagulation process. The method was validated using three known thrombin
      inhibitors: 4-(2-aminoethyl) benzenesulfonyl fluoride (IC50: 0.01 mM), p
      amidinophenyl methanesulfonyl fluoride (IC50: 0.18 mM) and PMSF (IC50: 0.23 mM). 

PMID- 24101249
TI  - Basic fibroblast growth factor-loaded, mineralized biopolymer-nanofiber scaffold
      improves adhesion and proliferation of rat mesenchymal stem cells.
AB  - Nanofibrous matrices are attractive scaffolding platforms for tissue
      regeneration. Modification of the nanofiber surface, particularly with biological
      proteins, improves cellular interactions. Here, we loaded basic fibroblast growth
      factor (bFGF) onto mineralized nanofibers and investigated the effect on adhesion
      and proliferation of rat mesenchymal stem cells. bFGF loading was significantly
      higher on the mineralized nanofiber than on the non-mineralized one. Release of
      bFGF from the mineralized nanofibers was continuous over 2 weeks. Cells cultured
      on the bFGF-loaded nanofiber attached and proliferated in significantly higher
      numbers than those on the bFGF-free nanofiber. bFGF-receptor inhibition study
      confirmed the biological role played by the loaded bFGF. This study details the
      advantages of the mineralized nanofiber surface for the loading and delivery
      bFGF, and thus the bFGF-loaded nanofiber scaffold may be useful for tissue repair
      and regeneration. 

PMID- 24101250
TI  - Biosynthesis of terephthalic acid, isophthalic acid and their derivatives from
      the corresponding dinitriles by tetrachloroterephthalonitrile-induced Rhodococcus
      sp.
AB  - The nitrilase from Rhodococcus sp. CCZU10-1 catalyses the hydrolysis of
      dinitriles to acids without the formation of amides and cyanocarboxylic acids. It
      was induced by benzonitrile and its analogues (tetrachloroterephthalonitrile >
      epsilon-caprolactam > benzonitrile > phenylacetonitrile), and had activity
      towards aromatic nitriles (terephthalonitrile > tetrachloroterephthalonitrile >
      isophthalonitrile > tetrachloroisophthalonitrile > tetrafluoroterephthalonitrile
      > benzonitrile). After the optimization, the highest nitrilase induction [311
      U/(g DCW)] was achieved with tetrachloroterephthalonitrile (1 mM) in the medium
      after 24 h at 30  degrees C after optimum enzyme activity was at pH 6.8 and at 30
      degrees C. Efficient biocatalyst recycling was achieved by cell immobilization
      in calcium alginate, with a product-to-biocatalyst ratios of 776 g terephthalic
      acid/g DCW and 630 g isophthalic acid/g DCW. 

PMID- 24101251
TI  - Aligning cells in arbitrary directions on a membrane sheet using locally formed
      microwrinkles.
AB  - Sheets of cells can be used for tissue regenerative medicine. Cell alignment
      within the sheet is now a key factor in the next generation of this technology.
      Anisotropic cell sheets without random cell orientations have been conventionally
      produced with photolithographically, microfabricated substrates using special
      facilities and equipment. Here we demonstrate a more accessible approach to the
      fabrication of anisotropic substrates. We locally deformed part of an elastic
      membrane and simultaneously oxidized the surface to create microwrinkles as well
      as to enable adhesion to the extracellular matrix. The approach with the local
      loading made it possible to orient cells in controlled directions within a single
      membrane sheet depending on the strains determined by the controllable
      deformation. This technique potentially enables a versatile design of
      microwrinkles for target-compatible cell alignments. 

PMID- 24101252
TI  - Biostimulation of indigenous communities for the successful dechlorination of
      tetrachloroethene (perchloroethylene)-contaminated groundwater.
AB  - Chlorinated ethenes are of environmental concern with most reports of successful
      microbial-mediated remediation being associated with major dechlorinating groups
      such as Dehalococcoides (Dhc) species. However, limited information is available
      on the community dynamics and dechlorinating activities of indigenous non-Dhc
      groups. Here, we present evidence of dechlorination of tetrachloroethene
      (perchloroethylene, PCE) in groundwater samples by indigenous microbial
      communities. 100 % PCE conversion to ethene was observed in acetate-stimulated 24
      week-microcosms (controls; 15 %). Microbial community profiles showed dominance
      by groups such as Proteobacteria, Spirochaetes, Firmicutes, Methanomicrobiaceae
      and Methanosarcinaceae. Pareto-Lorenz (PL) analyses suggested an adapted (45 % PL
      value) but variable bacterial community (55.5 % Delta t(week)) compared to
      Archaea (25 % PL value; 46.9 % Delta t(week)). Our findings provide evidence of
      dechlorinating potential of indigenous microorganisms and useful information on
      their dynamics which may be exploited for in situ groundwater bioremediation. 

PMID- 24101254
TI  - Improving smooth muscle cell exposure to drugs from drug-eluting stents at early
      time points: a variable compression approach.
AB  - The emergence of drug-eluting stents (DES) as a viable replacement for bare metal
      stenting has led to a significant decrease in the incidence of clinical
      restenosis. This is due to the transport of anti-restenotic drugs from within the
      polymer coating of a DES into the artery wall which arrests the cell cycle before
      restenosis can occur. The efficacy of DES is still under close scrutiny in the
      medical field as many issues regarding the effectiveness of DES drug transport in
      vivo still exist. One such issue, that has received less attention, is the
      limiting effect that stent strut compression has on the transport of drug species
      in the artery wall. Once the artery wall is compressed, the stents ability to
      transfer drug species into the arterial wall can be reduced. This leads to a
      reduction in the spatial therapeutic transfer of drug species to binding sites
      within the arterial wall. This paper investigates the concept of idealised
      variable compression as a means of demonstrating how such a stent design approach
      could improve the spatial delivery of drug species in the arterial wall. The
      study focused on assessing how the trends in concentration levels changed as a
      result of artery wall compression. Five idealised stent designs were created with
      a combination of thick struts that provide the necessary compression to restore
      luminal patency and thin uncompressive struts that improve the transport of drugs
      therein. By conducting numerical simulations of diffusive mass transport, this
      study found that the use of uncompressive struts results in a more uniform
      spatial distribution of drug species in the arterial wall. 

PMID- 24101253
TI  - Small molecule inhibitors of zinc-dependent histone deacetylases.
AB  - Lysine acetylation is an ancient, evolutionarily conserved, reversible post
      translational modification. A multitude of diverse cellular functions are
      regulated by this dynamic modification, including energy and metabolism, protein
      folding, transcription, and translation. Gene expression can be manipulated
      through changes in histone acetylation status, and this process is controlled by
      the function of 2 opposing enzymes: histone acetyl transferases and histone
      deacetylases (HDACs). The zinc-dependent HDACs are a family of hydrolases that
      remove acetyl groups from lysines, and their function can be modulated by the
      action of small molecule ligands. Inhibition through competitive binding of the
      catalytic domain of these enzymes has been achieved by a diverse array of small
      molecule chemotypes. Structural biology has aided the development of potent, and
      in some cases highly isoform-selective, inhibitors that have demonstrated utility
      in a number of neurological disease models. Continued development and
      characterization of highly optimized small molecule inhibitors of HDAC enzymes
      will help refine our understanding of their function and, optimistically, lead to
      novel therapeutic treatment alternatives for a host of neurological disorders. 

PMID- 24101255
TI  - Cardiac electrical conduction, autonomic activity and biomarker release during
      recovery from prolonged strenuous exercise in trained male cyclists.
AB  - PURPOSE: Although markers of myocyte injury, electrolyte disturbances and an
      autonomic imbalance have been reported following exercise, the effect of
      prolonged strenuous activity on cardiac electrical conduction is not well
      understood. This study examined atrial and ventricular conduction dynamics during
      recovery from exercise. METHODS: Electrocardiographic intervals were obtained
      from eight highly-trained males before, during recovery (15, 30, 45 and 60 min
      post-exercise) and 24 h after a prolonged bout of strenuous exercise. Time
      domain, frequency-domain and non-linear analyses of the RR, PR and QT intervals
      were analysed to investigate the effect of exercise on autonomic modulation and
      cardiac electrical conduction. Serum electrolyte and high-sensitivity cardiac
      troponin T (hs-cTnT) concentrations were measured before exercise, and after 60
      min and 24 h of recovery. RESULTS: The root mean square of the successive
      differences of RR, PR and QT intervals was significantly reduced during recovery
      (p < 0.05). Normalised low- and high-frequency power of RR intervals
      significantly increased and decreased, respectively, during recovery. Approximate
      entropy of PR and QT intervals, and the QT-variability index significantly
      increased during recovery. All measures except mean QT interval (pre 422 +/- 10
      ms vs 24 h post 442 +/- 11 ms, p = 0.013) returned to pre-exercise values after
      24 h. Serum hs-cTnT was significantly elevated 60 min after exercise (pre 5.2 +/-
      0.7 ng L(-1) vs 60 min post 27.4 +/- 6.2 ng L(-1), p = 0.01) and correlated with
      exercising heart rate (R(2) = 0.89, p < 0.001). Serum electrolyte concentrations
      were unchanged (p > 0.05). CONCLUSION: The results suggest suppressed
      parasympathetic and/or sustained sympathetic modulation of heart rate during
      recovery, concomitant with perturbations in atrial and ventricular conduction
      dynamics. Exercise-induced hs-cTnT release was heart rate dependent.

PMID- 24101256
TI  - Health journalists' perceptions of their communities and implications for the
      delivery of health information in the news.
AB  - Journalists have a unique opportunity to educate the community about public
      health and health care. In order for health communication messages to be
      effective, characteristics of the intended audience must be considered. Limited
      attention has been given to health journalists' perceptions of their target
      communities and little is known about how journalists' perceptions may impact the
      delivery of health information in the news. Fifteen in-depth telephone interviews
      were conducted with health journalists from varying geographic regions and media
      market sizes. Interview questions examined health journalists' perceptions of
      their target communities, the content and delivery of their health-related
      stories, and the current state of health journalism. Interviews were audio
      recorded for transcription and thematic analysis. Health journalists perceived
      their audiences to be primarily mothers and adults with limited education.
      Participants reported they often used personal stories and strong headlines to
      engage their communities. They also stated that their news stories were quite
      technical and may not have been written at an appropriate reading level for their
      audience. When asked about the current state of health journalism, participants
      reported that there were areas for improvement. Journalists stated that increased
      collaborations with public health practitioners would improve their own
      understanding of health and medical information and allow them to develop health
      news content that was more appropriate for their target communities.

PMID- 24101257
TI  - Erratum to: Pharmacodynamic effects of EV-077 in patients with diabetes mellitus
      and coronary artery disease on aspirin or clopidogrel monotherapy: results of an
      in vitro pilot investigation.

PMID- 24101259
TI  - Correlation of matrix metalloproteinase-3 expression with patient age, magnetic
      resonance imaging and histopathological grade in lumbar disc degeneration.
AB  - AIM: The purpose of the present study is to analyze the expression of matrix
      metalloproteinase-3 (MMP-3), magnetic resonance imaging (MRI) grading and
      histopathological alterations of the intervertebral disc (IVD) for correlations
      with each other and with the age, gender and low back pain duration of the
      patients who had undergone operations for lumbar disc herniation (LDH). MATERIAL
      AND METHODS: Forty-two patients were admitted to our clinic with signs of LDH and
      underwent surgery for LDH at 48 IVD levels. In all cases, specimens for
      histological and immunohistochemical analyses were removed from the IVD space.
      Lumbar IVD degeneration on MRI of the 48 IVDs from which surgical specimens had
      been obtained was classified into five grades using the Pfirrmann classification.
      RESULTS: In the degenerated IVD, the expression of MMP-3, MRI grading and
      histopathological alterations of the IVD displayed significant correlation.
      Increased age is closely related with aforementioned alterations. There was no
      correlation between MMP-3 expression and age, gender and duration of the pain.
      CONCLUSION: For evaluating and treating IVD degeneration, MRI is a good and non
      invasive diagnostic tool to determine the severity of degeneration. MMP-3 may be
      a therapeutic target of the degenerated IVD.

PMID- 24101258
TI  - The new landscape of therapy for myelofibrosis.
AB  - The landscape of therapy for myelofibrosis (MF) is evolving at a pace not
      previously seen for this clonal myeloproliferative neoplasm. The discovery of the
      JAK2 V617F mutation in 2005 has led to the rapid development of therapy
      specifically developed for afflicted MF patients. Indeed, the successful phase
      III studies of ruxolitinib demonstrating improved symptomatic burden,
      splenomegaly and survival led to the first approved myelofibrosis drug in the
      United States and Europe. Multiple additional JAK2 inhibitors are currently in or
      nearing phase III testing, including SAR302503 (fedratinib), SB1518 (pacritinib)
      and CYT387 (momelotinib), seeking to offer incremental benefits to ruxolitinib in
      regards to cytopenias or other disease features. In parallel, phase III testing
      of pomalidomide is ongoing, with the goal of solidifying the role of
      immunomodulatory therapy in MF-associated anemia. Multiple single agents
      strategies are ongoing with histone deacetylase inhibitors, hedgehog inhibitors
      and hypomethylation agents. Incremental advances are further sought, either in
      additive or synergistic fashion, from combination strategies of ruxolitinib with
      multiple different approaches ranging from allogeneic stem cell transplant to
      current therapies mitigating anemia and further impacting the bone marrow
      microenvironment or histology. Transitioning from a pre-2011 era devoid of
      approved MF therapies to one of multiple agents that target not only disease
      course but symptomatic burden has indeed changed the platform from which MF
      providers are able to launch individualized treatment plans. In this article, we
      discuss the diagnostic and therapeutic milestones achieved through MF research
      and review the emerging pharmacologic agents on the treatment horizon.

PMID- 24101260
TI  - Supraorbital keyhole approach for anterior circulation aneurysms.
AB  - AIM: Supraorbital keyhole approach provides access to the major part of the
      anterior circulation aneurysms. Herein, our surgical experience of supraorbital
      keyhole approach and its some modification have been proposed. MATERIAL AND
      METHODS: Out of a series of 76 patients harboring 80 aneurysms operated on via a
      supraorbital keyhole approach with a superciliar or front wrinkle skin incision,
      there are 70 patients with subarachnoidal bleeding, others are nonruptured
      aneurysms, Intraoperative rupture occurred in 8 cases, and 4 had multiple
      aneurysms. RESULTS: There was a good cosmetic results with less approach-related
      complications .Of 80 aneurysms, 75 aneurysms were clipped successfully by the
      supraorbital route. Good Glasgow Outcome Scale scores of 4 or 5 were achieved in
      95% of the patients at the time of discharge. 2 patients of Grade IV died in the
      postoperative period due vasospasm. CONCLUSION: The supraorbital route is
      recommended for selected anterior circulation aneurysms based on the improved
      surgical instruments and microsurgical skills.

PMID- 24101261
TI  - Endonasal endoscopic skull base multilayer reconstruction surgery with nasal
      pedicled mucosal flap to manage high flow CSF leakage.
AB  - AIM: Multilayer reconstruction of skull base using nasal pedicled mucosal flap
      has been widely accepted as a standard method for repairing high flow
      cerebrospinal fluid [CSF] leakage. In this study, we analyzed our outcome and
      summarized several valuable operation experiences from this technique. MATERIAL
      AND METHODS: This study included 20 consecutive patients who underwent endoscopic
      endonasal multilayer reconstruction using a nasal pedicled mucosal flap to repair
      high flow CSF leakage and were available for follow-up. RESULTS: In this series,
      all cases encountered intraoperative high-flow CSF leakage, including 11 (55%)
      patients with opening of third ventricles (TV) and 9 (45%) patients with wide
      opening of cistern (CS). After endoscopic endonasal multilayer reconstruction
      with nasal pedicled mucosal flap, 3 patients (15.0%) encountered CSF leakage in
      the early postoperative period but were successfully repaired; 2 patients (10.0%)
      encountered late postoperative CSF leakage. In the TV group, the ratio of CSF
      leakage was 18.2% (2/11); while the incidence of CSF leakage was 11.1% (1/9) in
      the CS group. One patient developed meningitis due to CSF leakage four month
      after surgery, then gave up treatment and died. CONCLUSION: Multilayer
      reconstruction with nasal pedicled flap seems to be useful and reliable for the
      treatment of ventral skull base defects using endoscopic endonasal approach.

PMID- 24101262
TI  - Pineal epidermoid tumors: report of five cases.
AB  - AIM: The aim of this study was to retrospectively analyse the clinical,
      radiological features and surgical outcome of pineal epidermoid tumors treated at
      a single neurosurgical department. MATERIAL AND METHODS: We performed surgery on
      five patients with pineal region epidermoid tumors at a single neurosurgical
      department between the years 1998 and 2006. Headache, diplopia and ataxia were
      the most common presenting findings. Parinaud's syndrome was found in three
      patients. Hydrocephalus was demonstrated radiologically in two patients. RESULTS:
      Two patients were operated on with the occipital-transtentorial approach, two
      were operated on with the infratentorial-supracerebellar approach and one was
      operated on with van Wagenen's approach. Recurrence of tumor was observed in one
      patient. One patient died at the first postoperative month due to ventriculitis.
      CONCLUSION: Total removal of epidermoid tumors may provide good clinical recovery
      and may reduce the possibility of tumor recurrence and shunt placement.

PMID- 24101263
TI  - The effects of vagal nerve stimulation in focal cerebral ischemia and reperfusion
      model.
AB  - AIM: This study aimed to investigate the effects of VNS in transient middle
      cerebral artery occlusion and reperfusion (MCAO/R) rat model of ischemia based on
      behavioral, morphological, and molecular approaches. MATERIAL AND METHODS: Wistar
      albino rats were divided into 3 groups: ischemia-reperfusion (I/R), I/R+VNS, and
      sham (for I/R). Each group was further divided into two subgroups for the
      assessment of neurological deficits and infarct area, or biochemical parameters
      related to oxidative stress. RESULTS: The infarct area and neurological scores
      were significantly lower in I/R+VNS group compared with the I/R group. MDA levels
      were significantly higher in I/R group compared to control and I/R+VNS groups in
      the cortical and subcortical specimens. There were also betweengroup differences
      in terms of GSH levels. GSH levels were higher in sham group compared with and
      I/R and I/R+VNS groups in cortical specimens whereas these levels for lower in
      I/R group compared to control and I/R+VNS groups in the subcortical specimens.
      SOD activity was higher in control group compared to I/R and I/R+VNS groups both
      in the cortical and subcortical specimens. There was no difference between I/R
      and I/R+VNS groups in neither cortical nor subcortical specimens. CONCLUSION: The
      neuroprotective and antioxidant properties of VNS suggest its efficacy as a
      potential anti-ischemic treatment.

PMID- 24101264
TI  - Routine postoperative CT-scans after burr hole trepanation for chronic subdural
      hematoma - better before or after drainage removal?
AB  - AIM: To evaluate timing of scheduled CT-scans after burr hole trepanation for
      chronic subdural hematoma (cSDH). MATERIAL AND METHODS: 131 patients with primary
      cSDH were included. Scheduled CT-scans were performed after burr hole trepanation
      and placement of a subdural drain. The influence of CT-scanning with or without
      indwelling drain was analysed regarding subsequent surgery and CT-scans, duration
      of hospitalization, short- and middle-term follow up by single factor analyses.
      Subgroup analyses were performed for patients receiving anticoagulant drugs.
      RESULTS: Median age was 74 years. Routine CT-scans with indwelling drainage were
      not shown to be beneficial regarding subsequent burr hole trepanations (p=0.243),
      craniotomies (p=1.000) and outcome at discharge (p=0.297). Mean duration of
      hospitalization (11 vs. 8 days, p=0.013) was significantly longer and number of
      subsequent CT-scans was higher when CT scan was performed with indwelling drain
      (2.3 vs. 1.4, p=0.001). In middle-term follow-up, beneficial effects of CT
      scanning with inlaying drainage could neither be shown. Moreover, advantageous
      effects of CT-scans with indwelling drains could neither be shown for patients
      receiving anticoagulant drugs. CONCLUSION: Scheduled postoperative cranial
      imaging with indwelling drains was not shown to be beneficial and misses
      information of intracranial damage inflicted by removal of drains. We thus
      recommend CT-scanning after drainage removal.

PMID- 24101265
TI  - Investigation of ACE genome insertion/deletion correlation with
      immunohistochemical profile in pituitary adenomas.
AB  - AIM: The deletion polymorphism of the angiotensin-converting enzyme (ACE) genome
      causes neoplastic development in several organs by increasing the angiotensin 2
      (A2) formation. In this study, we aimed to identify the ACE genome
      insertion/deletion polymorphism in pituitary adenomas and to compare it with the
      control group. MATERIAL AND METHODS: Patients operated for pituitary adenomas
      were included in the study. Genomic DNA was extracted from tumoral tissues and
      peripheral blood samples of the patients by using the Miller method. Primary
      sequence was selected via targeting the polymorphic region of intron 16 of ACE
      genome 17q23. DNA samples were multiplied by PCR using HACE3s and HACE3as
      primers. RESULTS: Twenty-one operated cases were studied. In the study group; 44
      % of the patients were identified as D/D, 33% of them as I/D and 23% of them as
      I/I. In 60%, D allele was identified. According to immunohistochemical
      investigation, we found that 100% of the patients with Cushing adenoma were D/D
      alleles. CONCLUSION: Presence of high rate of ACE genome deletion in patients
      with pituitary adenoma and grade 3-4 patients suggest that ACE genome
      polymorphism can be a risk factor for the development of pituitary adenomas.

PMID- 24101266
TI  - Management of Brown-Sequard syndrome in cervical disc diseases.
AB  - AIM: To raise the awareness of the appropriate management of unusual clinical
      presentation of cervical disc herniation. MATERIAL AND METHODS: Seven patients
      with Brown-Sequard syndrome due to cervical disc herniation presented with Brown
      Sequard syndrome had been treated surgically as one of them treated with anterior
      cervical discectomy and three patients treated by anterior cervical discectomy
      and fusion while three of them have been treated by posterior laminectomy.
      RESULTS: Patients were 7 three of them were female and four were males and the
      mean age of our patients is 45.28 +/- 16.49 years ranged between 32 and 72 years.
      History of spinodegenerative disease in the form of chronic neck pain with or
      without brachialgia was found in 6/7 patients (85.7%) while history of trauma was
      found in 5/7 patients (71.4%). Most common affected level is C5-C6 disc Outcome
      after surgical treatment revealed complete recovery in 4/7 patients (57.1%) while
      incomplete recovery in 2 patients (28.6%) and no improvement in one patient
      (14.3%). CONCLUSION: Brown-Sequard syndrome is a rare presentation of cervical
      disc herniation but accurate diagnosis, and early anterior spinal cord
      decompression lead to complete recovery of these cases.

PMID- 24101267
TI  - Frequency, distribution and severity of prevalent osteoporotic vertebral
      fractures in postmenopausal women.
AB  - AIM: Assessment of previous vertebral fractures provides useful information to
      predict future fracture risk. This study aimed to determine the frequency,
      distribution and severity of prevalent osteoporotic vertebral fractures in
      postmenopausal women. MATERIAL AND METHODS: Data on patient characteristics, bone
      densitometry values, and spine radiographs (T2-L5) were reviewed in 232
      postmenopausal women admitted to our osteoporosis clinic. RESULTS: Prevalent
      vertebral fractures were detected in 28 (12.1%) women (95%CI: 7.8 16.3). Fifteen
      women (6.5%) had mild fractures and 13 (5.6%) had moderate or severe fractures
      according to Genant's semi-quantitative technique. The T-score was associated
      with the presence of prevalent vertebral fractures (OR= 0.61; 95%CI: 0.38-0.96,
      P= 0.034). The most frequently fractured vertebrae were T11 and T12, followed by
      T7 and T9. Sixty percent of fractures were wedge-type while 40% were biconcave.
      The frequency of wedge-type fractures at the T11-T12 levels (93.8%) was higher
      compared to that at all other levels (44.1%) (P= 0.001). CONCLUSION: We
      determined the frequency, distribution, and severity of prevalent fractures and
      identified certain distribution patterns of fracture locations and types. To
      verify our results and detect possible predictive factors for fracture risk,
      population-based larger trials are needed.

PMID- 24101268
TI  - Long-term prognosis after revascularization therapy in patients with
      atherothrombotic stroke.
AB  - AIM: Many guidelines recommend carotid endarterectomy (CEA) in symptomatic
      patients with carotid stenosis of greater than 70%, and carotid artery stenting
      (CAS) as an alternative to CEA. In our study, we evaluated the clinical
      characteristics of patients who underwent revascularizaton therapy. MATERIAL AND
      METHODS: We reviewed the files of 2369 patients with stroke followed in our
      cerebrovascular outpatient clinics since 1996. RESULTS: 92 patients were treated
      by revascularization therapy. A total of 41 patients had CEA, 42 patients had
      CAS, and 9 patients had vertebral artery stenting; and 77 patients were followed
      up for a mean period of 50.2+42.7 months (6 to 168 months). Recurrent stroke or
      TIA and deaths due to cerebrovascular diseases were similar between CEA and CAS
      patients. Myocardial infarction (including silent MI) and deaths due to
      cardiovascular diseases were more common in CAS group, though not significant.
      The deaths due to other diseases and other non-fatal complications were
      significantly more common in CEA patients. On the other hand, restenoses - all of
      which were radiological findings but asymptomatic - were more common in the CAS
      group. CONCLUSION: In this study we disclosed neither morbidity nor mortality
      discrepancies in long term among the patients who were treated with carotid
      endarterectomy (CEA) and carotid artery stenting (CAS).

PMID- 24101269
TI  - Surgical therapy for craniocerebral firearm injury.
AB  - AIM: The current study aims to explore the clinical characteristics of
      craniocerebral firearm injury and to improve the diagnosis and treatment of this
      condition. MATERIAL AND METHODS: Data from 56 patients with craniocerebral
      firearm injury were analyzed retrospectively for projectile types, traumatic
      conditions, and treatment approaches. RESULTS: 43 patients exhibited intracranial
      foreign body residence. Of them, 40 were subjected to complete foreign body
      removal and 2 to partial removal, leaving 1 without receiving removal treatment.
      54 patients (96.4%) survived and 2 (3.6%) died. Of the survivors, 36 (64.3%)
      recovered well, 15 (26.8%) were moderately disabled, 2 (3.6%) were severely
      disabled, and 1 (1.8%) lapsed into vegetative state. Patients receiving
      debridement within 8 h after injury had a significantly higher recovery rate than
      those receiving such treatment after 8 h (82.1% vs. 26.7%; P < 0.001).
      CONCLUSION: Craniocerebral firearm injury is characterized by rapid traumatic
      condition development as well as serious trauma and contamination. Accurately
      judging the traumatic condition and the ballistic tract, performing complete
      debridement as early as possible, reasonably deciding on the operative mode and
      approach for intracranial residing foreign body removal, and increasing vigilance
      regarding concomitant injuries are the keys to the improvement of the overall
      treatment of craniocerebral firearm injury.

PMID- 24101270
TI  - Headache and its effects on health-related quality of life among adults.
AB  - AIM: This study was conducted with aim of determining prevalence of headache and
      evaluating its effects on health-related quality of life (HRQoL) in Beylikova
      town of Eskisehir city in the west of Turkey. MATERIAL AND METHODS: This study
      was conducted on adults aged 20 years and over aged between May 11 and June 04
      2009 in Beylikova town of Eskisehir city in the west of Turkey. A total of 587
      people were selected by simple randomized method. The International Headache
      Society criteria were used for the determination of severity of headache. The 36
      item short-form (SF-36) was used for the assessment of healthrelated quality of
      life. RESULTS: The number of men and women was 302 (51.4%), and 285 (48.6%),
      respectively. The mean age was 46.70 +/- 15.26 years (range, 20-87 years).
      Headache prevalence was found to be 78.2% (n=459). Decreased headache prevalence
      was found in the ages older than 30-44 age group (p < 0.05). All domains of SF
      36, the mean scores were higher in individuals without headache than those with
      headache (for each, p < 0.05). Migraine prevalence was found to be 7.2% (n=33).
      CONCLUSION: In accordance with the literature, this study found the presence of
      headache in adults at high frequency (78.2%). Particularly the presence of
      migraine and increased severity of headache were found to decrease the quality of
      life.

PMID- 24101272
TI  - Isolated intracranial Rosai-Dorfman disease: report of two cases and a review of
      the literature.
AB  - Rosai-Dorfman disease (RDD) is a rare but well-recognized idiopathic
      histioproliferative disease affecting the systemic lymph nodes. It is
      characterized by an unusual proliferation of histiocytic cells. Intracranial
      localization is a rare manifestation of RDD. The clinical and radiological
      differentiation from meningiomas is difficult, and can only be achieved after
      histological examination. This entity should be considered in the differential
      diagnosis of dural based lesions mimicking meningioma. We report 2 cases of
      isolated intracranial RDD. The first patient had a large frontal lesion in
      addition to smaller multiple intracranial lesions. The second patient had only
      one parasagittal lesion. The diagnosis was confirmed on histopathological
      examination after surgical excision. The pertinent literature is also reviewed. 

PMID- 24101271
TI  - Primary multiple cerebral hydatid disease: still symptomatic despite
      pathologically confirmed death of the cyst.
AB  - Hydatid disease is a life-threatening parasitic infestation caused by
      Echinococcus granulosus. Infection with E. granulosus typically results in the
      formation of hydatid cysts in liver, lungs, kidney and spleen. Majority of the
      intracranial cysts are secondary and solitary. Multiple primary cerebral cysts
      are uncommon. Surgical and medical management of a 14-year-old boy with multiple
      primary hydatid cysts are presented. 14 cysts, which were symptomatic due to
      their mass effect, were surgically removed, whereas a deep-seated asymptomatic
      cyst was followed-up with medical treatment. Despite proper antibiotic regimen
      the patient was admitted with epileptic seizures six months later. The deep
      seated lesion was also surgically removed. Intraoperative observations and
      pathological examination demonstrated different characteristics, with pericystic
      gliosis, gel-like cyst content and death scolices within the cavity. In addition
      to the fact, that the presented case is an additional example for the rare
      primary multiple cerebral hydatid cysts, to our knowledge it is the first case of
      a dead cerebral hydatid cyst, causing symptoms despite effective medical
      treatment.

PMID- 24101273
TI  - Compound elevated skull fracture: a clinical series of three patients with a
      review of the literature.
AB  - AIM: Compound elevated fracture of the skull is an unusual variety of fracture of
      the cranial vault that has been rarely described in the currently available
      literature. The authors describe three such patients with post-traumatic compound
      elevated skull fracture. The pertinent literature is reviewed, the injury
      mechanism is highlighted and the management issues are discussed in detail. CASE
      DESCRIPTION: All three patients in this series presented with elevation of free
      skull fracture fragments above the surface. The mode of injury was rail accident
      in two patients and injury by a rapidly moving crane in one patient. Two patients
      had dural laceration with extrusion of brain matter through the dural defect. The
      remaining patient had an elevated fracture fragment simulating a formal
      craniotomy with an intact dura. The patient who suffered crane injury was brought
      dead. Surgery was performed in remaining two patients. Wound debridement and
      duraplasty was performed. Both patients received broad-spectrum antibiotics in
      anti-meningitic doses. Both of these patients did well after surgery. CONCLUSION:
      Elevated skull fractures are usually compound injuries. High velocity tangential
      impact to the skull vault is the most likely causative mechanism in such type of
      injury. Delay in surgery could lead to intracranial sepsis including meningitis
      and brain abscess. Thus, these fractures should be aggressively treated.

PMID- 24101274
TI  - Thoracic vertebral hemangioma causing paraplegia in Klippel-Trenaunay-Weber
      syndrome: case report.
AB  - Vertebral hemangiomas are the most common tumours of the vertebral column.
      Generally, these tumours are asymptomatic but some patients complain of back pain
      and develop neurologic symptoms due to extraosseous extension. Vertebral
      hemangiomas can extend extradurally causing neurological impairment as a result
      of compression of the spinal cord and nerve roots. Vertebral hemangiomas may be
      multiple and detectable as a component of the Klippel-Trenaunay-Weber syndrome.
      Although this syndrome consists of deep venous thrombosis, lymphatic anomalies,
      cutaneous capillary malformations, and hypertrophy of soft tissue and bone on
      extremities, its clinical presentation may be very variable. We present a unique
      case of vertebral hemangioma causing spinal cord compression due to the
      extradural extension that also had deep venous thrombosis, hematuria, hypophyseal
      cyst and ventricle asymmetry, diagnosed as the Klippel-Trenaunay-Weber syndrome. 

PMID- 24101275
TI  - A case of adult onset medulloblastoma during maintenance chemotherapy for
      anaplastic astrocytoma one year after radiotherapy.
AB  - Multiple primitive intracranial tumors with different histological
      characteristics are uncommon. Although coexistence of a medulloblastoma with
      glial tumors has been reported in children, medulloblastoma is rarely found in
      adults, especially those older than 40 years of age. We present an extremely rare
      case of a medulloblastoma developing in a 40-year-old male undergoing maintenance
      chemotherapy for anaplastic astrocytoma for 21 months after radiotherapy.
      Initially, he complained of intractable epilepsy characterized by complex partial
      seizures. Magnetic resonance imaging (MRI) revealed a slightly enhanced mass
      lesion in the left insula region. He underwent subtotal removal of the tumor and
      it was histologically diagnosed as anaplastic astrocytoma. After 19 months of
      treatment with temozolomide (TMZ) and radiotherapy, he presented with vertigo and
      headache. A homogeneously enhanced mass had developed in the left cerebellar
      hemisphere. He received gross total resection of the second tumor, pathologically
      diagnosed as medulloblastoma. In conclusion, this is the first case report of an
      adult medulloblastoma coexisting with anaplastic astrocytoma. 

PMID- 24101276
TI  - Acromegaly associated with mixed pituitary adenoma-gangliocytoma and Rathke's
      cleft cyst.
AB  - Gangliocytoma of the pituitary gland is a rare lesion that often occurs in
      combination with pituitary adenomas and the exact origin is the subject of
      discussion. We report a rare case of an intrasellar mass of combined
      gangliocytoma/ pituitary adenoma coexistent with Rathke's cleft cyst. A 50-year
      old female was admitted to our hospital with headache, mild acromegaly, and
      bitemporal hemianopsia. Histologically the tumor was composed of triphasic
      component of pituitary adenoma, clusters of ganglion cells and small cysts
      embedded in a variably dense neuropil substrate. Immunohistochemical analysis
      revealed the ganglion cells and adenoma cells were positive for synaptophysin and
      neurofilament. The lining of Rathke's cleft cyst was immunoreactive for
      cytokeratin 8. The exact pathogenesis of combined sellar pathology is not clear
      yet. However, a common stem/progenitor cell origin of both the adenomatous and
      neuronal component of these lesions has been suggested. 

PMID- 24101277
TI  - Traumatic pseudoaneurysm of the superficial temporal artery: a case report.
AB  - Pseudoaneurysms of superficial temporal artery are very rare and commonly occur
      as a result of blunt trauma. There are several methods for the diagnosis, but the
      diagnosis can be accurately made only from a history and physical examination. A
      27-year-old man presented with a painless pulsatile mass over his right temporal
      region after a blunt head trauma. The diagnosis was suspected to be superficial
      temporal artery pseudoaneurysm. The patient underwent surgical exploration and
      the mass was resected. Histopathological findings confirmed the diagnosis of
      pseudoaneurysm. Superficial temporal artery pseudoaneurysm can be easily
      diagnosed through an accurate history and physical examination alone. Diagnostic
      methods can be used in complicated cases. 

PMID- 24101278
TI  - Multiple spinal cord melanoma: case report with emphasis on the difficult
      preoperative diagnosis.
AB  - Primary spinal melanoma (PSM) is rare and usually occurs in the cervical and
      thoracic regions. Here, we present a case of multiple spinal cord melanoma
      located at the level of cervical and upper thoracic spine in a 24-year-old male.
      The patient underwent a T6-T7 thoracic laminectomy and gross-total resection of
      the duty lesion. The histological findings of the tumor were consistent with an
      intermediate-grade melanocytoma. To the best of our knowledge, only two cases of
      multifocal primary melanocytic tumor have been reported in the literature. In
      this case study we review the pertinent literature and emphasize the importance
      and difficulties concerning the preoperative diagnosis of multiple PSM. 

PMID- 24101279
TI  - Craniovertebral junction melanocytoma: a case report.
AB  - Melanocytomas are rare melanocytic tumors of the central nervous system and its
      presence at the foramen magnum is extremely rare. We report a case of a 55-year
      old male presenting with progressive quadriparesis over one year. Imaging showed
      a well-defined intradural extramedullary lobulated mass at craniovertebral
      junction towards the left side and extending to left C2-3 neural foramina.
      Patient was operated through foramen magnum approach with near total excision of
      tumor. On a ten-month follow up, he was ambulatory with normal motor power on
      right side of body and left lower limb and with motor power of 4-/5 in left upper
      limb. Histopathology and immunohistochemistry confirmed the lesion to be a
      melanocytoma. 

PMID- 24101280
TI  - Intracerebellar hemispheres schwannoma: a case report.
AB  - Brain parenchyma schwannoma is a rare intracranial tumor, and especially rare in
      cerebellar hemisphere. In this report, a case of cerebellar schwannoma in a 52
      year-old woman, was studied by computed tomography (CT), magnetic resonance image
      (MRI) and PET-CT. This tumor was totally removed by surgery. The histological
      diagnosis of schwannoma was confirmed by histological, HE and immunohistological
      staining examination (positivity for the S-100 protein and vimentin, and partly
      positivity for P53 (70 %+), and negative for GFAP). The patient has been followed
      up for more than one year, and she lives in good condition and brain MRI shows no
      recurrence. Surgery is the most effective treatment for cerebellar schwannoma. 

PMID- 24101281
TI  - Moyamoya disease with posterior communicating artery aneurysm: a case report.
AB  - In moyamoya disease (MMD), subsequent aneurysm in the proximal part of the
      posterior communicating artery (PcomA) is extremely rare. We report the case of a
      middle-aged female patient with MMD, who presented with a ruptured wide-necked
      aneurysm at the proximal part of the developed PcomA that converged with the
      posterior cerebral artery (PCA) and supplied the distal area. Endovascular
      treatment was performed, but the stent-assisted coil embolization resulted in
      occlusion of the internal carotid artery (ICA) above the ophthalmic artery and
      PcomA. Due to good compensatory collateral circulation, the patient was improved
      after surgery and had no complications. One-year followup DSA did not show
      recurrence of the aneurysm. The right ICA was still embolized, but with good
      compensatory collateral circulation. We conclude that, for an MMD patient with an
      aneurysm at the proximal part of the developed PcomA, if the ICA and PcomA are
      accidentally occluded, then the patient may still have a good prognosis due to
      sufficient collateral blood circulation.

PMID- 24101282
TI  - A case of chordoma invading multiple neuroaxial bones: report of ten years follow
      up.
AB  - AIM: Chordoma is a rare, slow-growing primary malignant tumor of the axial
      skeleton, arising from the embryonic cells of primitive notochord. Chordomas may
      arise at different sites of the vertebral column simultaneously or more probably
      they may metastasise along the neural axis insidiously. Recurrence despite
      radical surgery and following adjuvant therapy is possible. MATERIAL AND METHODS:
      A 46-year-old female patient presented weakness and numbness of the lower
      extremities. She was operated for clivus chordoma five years ago at another
      institute. RESULTS: First the patient underwent surgery for resection of the
      tumor at the cervical region. a second surgery was performed to resect tumor on
      the foramen magnum and at the C1 level. Histologic examination of the removed
      vertebra confirmed the diagnosis of chordoma involving the vertebral body.
      Radiotherapy was administered after the second surgery. Follow-up neurological
      and radiological examinations revealed no abnormal neurological symptoms 2,5
      years after second surgery. There were no distant organ metastases. CONCLUSION: A
      patient with diagnosed chordoma of the spine must be investigated with MRI of
      other regions of the neuraxis to exclude second or even third source of chordoma
      metastases. In metastatic chordoma cases, radical or gross total resection should
      be performed for each lesion but if complete surgical resections are impossible,
      preoperative or postoperative radiation therapy should be planned to improve life
      expectancy.

PMID- 24101283
TI  - Ganglioglioma mimicking the cerebral abscess in advanced age: a case report.
AB  - Ganglioglioma is one of the rare mixed neuronal glial tumors of the central nerve
      system. It is responsible for 0.4 - 2% of the intracranial tumors observed in
      infants and young matures. Its most common localization is the supratentorial
      region. Typically, the first symptom is epilepsy. Due to the glial structure,
      that rare tumor can exhibit a malign transformation. Growing slowly through
      several months or years, it forms neurological dysfunction. The standard
      treatment of that supratentorial tumor is usually total resection. If an
      anaplastic quality is observed, the patient undergoes radiotherapy after the
      surgical intervention. In this article, we presented a 53-year-old patient who
      presented with headache and dysphasia. The patient was operated for the cystic
      mass in the left parietal lobe reported as an abscess. The pathology was reported
      as ganglioglioma and we discussed the case according to the literature. 

PMID- 24101284
TI  - Coma due to malplaced external ventricular drain.
AB  - Ventriculostomy or external ventricular drain (EVD) placement by free-hand
      technique has a high malplacement rate. It is a blind procedure that often
      requires multiple attempts and revisions. To date, no neurological complication
      due to EVD malplacement has been reported in the literature. In this report, we
      present the first case of coma induced by a malplaced EVD and the patient
      regained consciousness after the drain was adjusted. Our discussion focused on
      various techniques that can improve the accuracy of EVD insertion. EVD insertion
      under image guidance provides better accuracy with limited disadvantages. We
      hypothesized that the patient's coma was due to the mass effect and irritation of
      the malplaced EVD exerted onto the ventral periaqueductal grey matter and the
      ascending neurons from upper brainstem. 

PMID- 24101285
TI  - Emergency management of an acute tension pneumocephalus following
      ventriculoperitoneal shunt surgery for normal pressure hydrocephalus.
AB  - Tension pneumocephalus is a rare and life threatening complication of
      intracranial surgical procedures, and requires immediate recognition and surgical
      intervention. Tension pneumocephalus following ventriculoperitoneal shunt surgery
      is extremely rare and commonly seen as a delayed complication. To our knowledge,
      early postoperative tension pneumocephalus after shunt surgery was reported only
      in one other publication. We present a case of acute tension pneumocephalus
      following ventriculoperitoneal shunt surgery for normal pressure hydrocephalus,
      which was managed well with close neurological follow-up and rapid surgical
      intervention. The use of the portable CT scanner in this case saved significant
      time, without the transport of the patient to the radiology unit, made early
      surgical intervention possible, and prevented morbidity and mortality. 

PMID- 24101286
TI  - Fatal intracranial hemorrhage as the initial presentation of acute lymphocytic
      leukemia: a case report.
AB  - Hemorrhagic complications of acute leukemia are well described and are a common
      cause of mortality in these patients. However, to our knowledge, fatal
      intracerebral hemorrhage (ICH) as an initial presentation of acute lymphocytic
      leukemia (ALL) has only been reported once. We report a case of previously
      undiagnosed ALL presenting with ICH. Our patient is a 17-year old male who was
      found unresponsive several hours after complaining of headache. Initial emergency
      room evaluation found the patient to have anisocoria with a fixed and dilated
      right pupil and demonstrated evidence of decorticate posturing. Imaging revealed
      a large right-sided intraparenchymal hemorrhage, intraventricular hemorrhage,
      midline shift, and uncal herniation. Laboratory evaluation showed marked
      leukocytosis with blastic predominance and evidence of disseminated intravascular
      coagulopathy. Emergent surgical intervention was performed. However, despite
      evacuation of the hematoma, the patient eventually progressed to clinical brain
      death. Usually, ICH is seen in ALL patients after the diagnosis has been made. We
      report a unique case of fatal intracranial hemorrhage as the initial presentation
      of ALL and discuss the possible management dilemmas to treat such entities. ALL
      should be kept in the broad differential diagnosis of spontaneous ICH, especially
      in a young patient with evidence of severe coagulopathy. 

PMID- 24101287
TI  - Primary pineal glioblastoma: a case report.
AB  - Glioblastoma is very rare in the pineal region. We report a case of glioblastoma
      in this region. This is the 18th case of primary glioblastoma in the pineal
      region and the second case that survived over two years according the literature.
      A 60-year-old man admitted with headache and ataxia that continued for the last 3
      months. Physical examination was normal. Neurological examination revealed
      ataxia. There was no motor or sensory deficit. Computer tomography showed
      triventricular hydrocephalus and isodense rounded mass in the pineal region.
      Magnetic resonance images revealed a regular-edged heterogeneous contrast
      enhanced tumor in pineal region. A ventriculoperitoneal shunt was inserted for
      hydrocephalus. After surgery, the ataxia and hydrocephalus were improved. Ten
      days later, serial stereotactic biopsies were performed. Histopathological
      specimens revealed glioblastoma. The patient was recommended to undergo
      radiotherapy and chemotherapy. The patient is still surviving without deficit two
      years after biopsy and shunt operation. 

PMID- 24101288
TI  - Orbital eosinophilic granuloma in a child: a case report.
AB  - Eosinophilic granuloma is a rare disease belonging to the Langerhans' cell
      histiocytosis group. It accounts for only 1% of all tumor-like lesions of bone. A
      6-year-old girl presented with proptosis, and a mass and pain in her right eye.
      Cranial computerized tomography and magnetic resonance imaging revealed a mass in
      her right orbital area. The patient was operated through a right frontotemporal
      craniotomy and orbitozygomatic osteotomy. The tumour was totally removed. The
      postoperative course was uneventful. Histopathological examination revealed a
      diagnosis of eosinophilic granuloma with typical Langerhans cells and
      eosinophylic leucocyte infiltration. We report an orbital eosinophilic granuloma
      case, which is rarely seen, and discuss its clinical and pathological features.

PMID- 24101289
TI  - Focused opening of the sylvian fissure for microsurgical management of MCA
      aneurysms.
AB  - BACKGROUND: A wide sylvian opening, with either a proximal or distal start, has
      been standard for microsurgical management of middle cerebral artery (MCA)
      aneurysms. However, extensive sylvian dissection is potentially associated with
      increased incidence of iatrogenic injury to the brain and neurovascular
      structures. The aim of the present study was to describe the technique of focused
      opening of the sylvian fissure for microsurgical management of MCA aneurysms with
      additional tips on handling difficulties which may be encountered with this
      technique. METHOD: A 3D image-based anatomic orientation, clipping field-focused
      surgical planning, slack brain, and high magnification are the basic requirements
      for this approach. A 10-15 mm sylvian opening is placed so that it allows safe
      access and a good surgical view of the MCA aneurysm clipping field. Under
      proximal control of the MCA, the aneurysm neck can be dissected and clipped
      effectively and safely, in this small surgical field. RESULTS: The presented
      technique has been developed and refined by the senior author during the surgery
      of 1,097 aneurysms over the last 13 years. It has proved to be safe, and
      effective for clipping of both ruptured and unruptured MCA aneurysms. Its
      greatest advantages are a shorter operative time and less brain and vessel
      manipulation compared to more extensive approaches. CONCLUSION: The focused
      sylvian opening is a less-invasive alternative to the classical wide sylvian
      opening for the microsurgical management of most MCA aneurysms.

PMID- 24101290
TI  - Complete bilateral arcuate foramina and atlantoaxial subluxation.

PMID- 24101291
TI  - Trepanation and surgical infection in the 18th century.
AB  - BACKGROUND: It is widely believed that trepanation prior to modern surgical
      hygiene was dangerous because of surgical infection, especially in the hospital.
      There has been a wide variability in the success and risks of different
      historical studies PURPOSE: To obtain a more accurate assessment of the risks of
      post-operative infection following 18th-century cranial trauma and to note what
      factors were of prognostic significance. MATERIAL AND METHODS: Seven 18th-century
      texts on head injury are reviewed and analyzed. RESULTS: Infection was the
      commonest cause of death (in over 60% of patients) in five series but not in the
      other two. Hospital admission did not appear to be a major factor influencing
      mortality from infection. Delayed infection was the indication for patient
      referral and trepanation in more than two patients in two series. In one series,
      the patients were helped by the procedure, in the other they were not. The
      reasons for the difference are discussed. The most striking finding was that
      patients treated in rural areas had a much better prognosis. CONCLUSIONS: The
      risks of suffering a surgical infection following head injury and trepanation are
      multifactorial. Admission to hospital seems to have been less risky than has been
      previously thought. It seems that the greatest risk factor for a lethal infection
      for these patients was living in an urban environment.

PMID- 24101293
TI  - Prefrontal cortex activated bilaterally by a tilt board balance task: a
      functional near-infrared spectroscopy study in a semi-immersive virtual reality
      environment.
AB  - The aim of this study was to assess the prefrontal cortex (PFC) oxygenation
      response to a 5-min incremental tilt board balance task (ITBBT) in a semi
      immersive virtual reality (VR) environment driven by a depth-sensing camera. It
      was hypothesized that the PFC would be bilaterally activated in response to the
      increase of the ITBBT difficulty, given the PFC involvement in the allocation of
      the attentional resources to maintain postural control. Twenty-two healthy male
      subjects were asked to use medial-lateral postural sways to maintain their
      equilibrium on a virtual tilt board (VTB) balancing over a pivot. When the
      subject was unable to maintain the VTB angle within +/- 35 degrees  the VTB
      became red (error). An eight-channel fNIRS system was employed for measuring
      changes in PFC oxygenated-deoxygenated hemoglobin (O2Hb-HHb, respectively).
      Results revealed that the number of the performed board sways and errors
      augmented with the increasing of the ITBBT difficulty. A PFC activation was
      observed with a tendency to plateau for both O2Hb-HHb changes within the last 2
      min of the task. A significant main effect of the level of difficulty was found
      in O2Hb and HHb (p < 0.001). The study has demonstrated that the oxygenation
      increased over the PFC while the subject was performing an ITBBT in a semi
      immersive VR environment. This increase was modulated by the task difficulty,
      suggesting that the PFC is bilaterally involved in attention-demanding tasks.
      This task could be considered useful for diagnostic testing and functional
      neurorehabilitation given its adaptability in elderly and in patients with
      movement disorders.

PMID- 24101292
TI  - Emotional modulation of pain and spinal nociception in persons with severe
      insomnia symptoms.
AB  - BACKGROUND: Impaired sleep enhances pain, perhaps by disrupting pain modulation.
      PURPOSE: Given that emotion modulates pain, the present study examined whether
      emotional modulation of pain and nociception is impaired in persons with severe
      insomnia symptoms relative to controls. METHODS: Insomnia group (n = 12) met the
      International Classification of Diseases, tenth revision symptoms for primary
      insomnia and controls (n = 13) reported no sleep impairment. Participants were
      shown emotionally evocative pictures (mutilation, neutral, and erotica) during
      which suprathreshold pain stimuli were delivered to evoke pain and the
      nociceptive flexion reflex (NFR; physiological correlate of spinal nociception).
      RESULTS: Emotional responses to pictures were similar in both groups, except that
      subjective valence/pleasure ratings were blunted in insomnia. Emotional
      modulation of pain and NFR was observed in controls, but only emotional
      modulation of NFR was observed in insomnia. CONCLUSIONS: Consistent with previous
      findings, pain modulation is disrupted in insomnia, which might promote pain.
      This may stem from disrupted supraspinal circuits not disrupted brain-to-spinal
      cord circuits.

PMID- 24101294
TI  - Novel role of mechanosensitive AT1B receptors in myogenic vasoconstriction.
AB  - Myogenic vasoconstriction is an inherent property of vascular smooth muscle cells
      (VSMCs) of resistance arteries harboring ill-defined mechanosensing and
      mechanotransducing elements. G protein-coupled receptors (GPCRs) are discussed as
      mechanosensors in VSMCs. In this study, we sought to identify and characterize
      the role and impact of GPCRs on myogenic vasoconstriction. Thus, we analyzed mRNA
      expression levels of GPCRs in resistance versus preceding conduit arteries
      revealing a significant enrichment of several GPCRs in resistance vessels.
      Selective pharmacological blockade of the highly expressed GPCRs in isolated
      murine mesenteric arteries ex vivo decreased myogenic vasoconstriction. In
      particular, candesartan and losartan most prominently suppressed myogenic tone,
      suggesting that AT1 receptors play a central role in myogenic vasoconstriction.
      Analyzing angiotensinogen(-/-) mice, a relevant contribution of locally produced
      angiotensin II to myogenic tone could be excluded. Investigation of AT1A (-/-)
      and AT1B (-/-) murine mesenteric arteries revealed that AT1B, but not AT1A,
      receptors are key components of myogenic regulation. This notion was supported by
      examining fura-2-loaded isolated AT1A (-/-) and AT1B (-/-) VSMCs. Our results
      indicate that in VSMCs, AT1B receptors are more mechanosensitive than AT1A
      receptors even at comparable receptor expression levels. Furthermore, we
      demonstrate that the mechanosensitivity of GPCRs is agonist-independent and
      positively correlates with receptor expression levels. 

PMID- 24101295
TI  - Enteric sensory neurons communicate with interstitial cells of Cajal to affect
      pacemaker activity in the small intestine.
AB  - Enteric sensory neurons (the AH neurons) play a role in control of
      gastrointestinal motor activity; AH neuron activation has been proposed to change
      propulsion into segmentation. We sought to find a mechanism underlying this
      phenomenon. We formulated the hypothesis that AH neurons increase local ICC-MP
      (interstitial cells of Cajal associated with the myenteric plexus) pacemaker
      frequency to disrupt peristalsis and promote absorption. To that end, we sought
      structural and physiological evidence for communication between ICC-MP and AH
      neurons. We designed experiments that allowed us to simultaneously activate AH
      neurons and observe changes in ICC calcium transients that underlie its pacemaker
      activity. Neurobiotin injection in AH neurons together with ICC
      immunohistochemistry proved the presence of multiple contacts between AH neuron
      varicosities and the cell bodies and processes of ICC-MP. Generating action
      potential activity in AH neurons led to increase in the frequency and amplitude
      of calcium transients underlying pacemaker activity in ICC. When no rhythmicity
      was seen, rhythmic calcium transients were evoked in ICC. As a control, we
      stimulated nitrergic S neurons, which led to reduction in ICC calcium transients.
      Hence, we report here the first demonstration of communication between AH neurons
      and ICC. The following hypothesis can now be formulated: AH neuron activation can
      disrupt peristalsis directed by ICC-MP slow wave activity, through initiation of
      a local pacemaker by increasing ICC pacemaker frequency through increasing the
      frequency of ICC calcium transients. Evoking new pacemakers distal to the
      proximal lead pacemaker will initiate both retrograde and antegrade propulsion
      causing back and forth movements that may disrupt peristalsis. 

PMID- 24101296
TI  - Clinical significance and positive correlation of FoxM1 and Her-2 expression in
      gastric cancer.
AB  - The transcription factor forkhead box protein M1 (FoxM1) and tyrosine kinase
      receptor Her-2, aberrantly expressing in various kinds of human malignancies, are
      closely related to the development of cancer. However, the correlation of them is
      still little explored, especially in gastric cancer. In current study, we
      examined FoxM1 and Her-2 levels in gastric cancers, and the clinical significance
      and association of them were further explored. As a result, FoxM1 and Her-2
      expression were significantly higher in gastric cancer compared with para-cancer
      tissues and gastric cell lines (P < 0.01), while a positive association was found
      between the two genes at both RNA and protein levels (P = 0.007, P = 0.025). No
      significant association was observed between FoxM1 expression and clinic
      pathological parameters (P > 0.1), whereas the positive frequency of Her-2
      correlated with TNM stage significantly (P = 0.045). In addition, multivariate
      analysis showed Her-2 was not a prognostic predictor in gastric cancer (P =
      0.625), while FoxM1 was independently associated with prognosis (P = 0.001),
      which especially affected the survival in patients with advanced stage (P <
      0.01). These results suggest that FoxM1 and Her-2 are important diagnostic
      markers for gastric cancer, and FoxM1 is a favorable prognostic indicator in
      gastric cancer. FoxM1 may be a potential cellular target for therapeutic
      intervention, especially in Her2-targeted therapy-resistant cancers.

PMID- 24101297
TI  - Gender differences in oxidative and nitrosative stress parameters in kidney
      transplant patients on tacrolimus-based immunosuppression.
AB  - BACKGROUND: Cardiovascular (CV) morbidity and mortality rates are still higher
      after kidney transplantation than in general population. It is known that
      oxidative and nitrosative stress may contribute to the progress of CV disease in
      a post-transplant period, but still gender aspect has not been elucidated
      completely. The aim of this study was to analyze the gender differences in the
      oxidative and nitrosative stress parameters, as well as asymmetric
      dimethylarginine (ADMA) and symmetric dimethylarginine (SDMA) levels among kidney
      transplant patients on tacrolimus-based immunosuppression. METHODS: Our research
      included 35 patients (20 men and 15 women) with renal transplant and 25 healthy
      volunteers. Patients were on chronic immunosuppressive regimen, which included
      tacrolimus, mycophenolate mofetil and prednisone. In order to estimate oxidative
      and nitrosative stress, we determined plasma levels of thiobarbituric acid
      reactive substances (TBARS), activity of catalase (CAT), levels of total (protein
      and non-protein) sulfhydryl (SH) groups, advanced oxidation protein products
      (AOPP), ADMA and SDMA, as well as nitrite/nitrate (NOx) ratio. RESULTS: TBARS,
      CAT and SH in plasma were significantly higher in male patients than in female
      patients (p < 0.05, p < 0.01 and p < 0.05, respectively). There were no gender
      dependent differences in AOPP, ADMA, SDMA and NOx in kidney transplant patients.
      Correlation analysis, Pearson and Spearman, showed significant correlations
      between tested oxidative and nitrosative stress parameters in male kidney
      transplant patients. Alternatively, in female patients, there were no significant
      correlations between tested parameters. CONCLUSION: Our findings show that men
      might be more prone to oxidative damage than women. ADMA, the proven marker of CV
      morbidity and mortality, may be more significant in male kidney transplant
      patients concerning oxidative stress control of its level and function.

PMID- 24101299
TI  - Abstracts of the 12th International Symposium on NeuroVirology. October 29
      November 2, 2013. Washington, D.C., USA.

PMID- 24101300
TI  - Marking Twain.
AB  - The first of the following two narratives is a personal reflection by the
      instructor of "Narrative Approaches to Bioethics," an elective in the PhD program
      at the Albert Gnaegi Center for Health Care Ethics at Saint Louis University. The
      author argues that perhaps the primary goal of medical ethics education should be
      to show how to construct plausible and defensible interpretations of human
      experience and sensibly resolve the problems that these happenings occasion. To
      that end, the author engaged the sympathetic reading capacities of his students
      by "thwarting" their expectations for medicalized case studies to "dissect" and
      instead chose works that invited careful readings of morally-complex literary
      works. One such reading was Huckleberry Finn, which the class read on the book's
      100(th) anniversary. Huckleberry Finn chronicles Huck's search for truth,
      goodness and justice on the Mississippi River-a location the class explored on a
      field trip. The second narrative is the personal reflection of one of the
      students in this class and attests to the moral pedagogical power of Huck Finn.
      He relates the insights gleaned from a particular passage where Huck confronts
      moralistic dogmas. 

PMID- 24101298
TI  - Genetic shift of env V3 loop viral sequences in patients with HIV-associated
      neurocognitive disorder during antiretroviral therapy.
AB  - The development of human immunodeficiency virus type 1 (HIV)-associated
      neurocognitive disorder (HAND) involves the adaptation of viral sequences coding
      for the V3 loop of the env protein. The plasma and cerebrospinal fluid (CSF) may
      contain viral populations from various cellular sources and with differing
      pathogenicity. Combination antiretroviral therapy (cART) may alter the relative
      abundance of these viral populations, leading to a genetic shift. We
      characterized plasma and CNS viral populations prior to and during cART and
      relate the findings to viral elimination kinetics and the clinical phenotype.
      Longitudinal plasma and CSF samples of five chronically infected HIV patients,
      four of whom had HAND, and one seroconverter were analyzed for V3 sequences by RT
      PCR and sequence analysis. In the chronically infected patients, pre-cART plasma
      and CSF viral sequences were different irrespective of viral elimination kinetics
      and clinical phenotype. cART induced replacement of plasma viral populations in
      all subjects. CSF viral populations underwent a clear genetic shift in some
      patients but remained stable in others. This was not dependent on the presence of
      HAND. The genetic shift of CSF V3 sequences was absent in the two subjects whose
      CSF viral load initially increased during cART. In one patient, pre- and post
      treatment CSF sequences were closely related to the post-treatment plasma
      sequences, suggesting a common cellular source. We found heterogeneous patterns
      of genetic compartmentalization and genetic shift over time. Although these did
      not closely match viral elimination kinetics and clinical phenotype, the results
      imply different patterns of the dynamics and relative contribution of compartment
      specific virus populations in chronic HIV infection.

PMID- 24101301
TI  - Indistinguishable synaptic pharmacodynamics of the N-methyl-D-aspartate receptor
      channel blockers memantine and ketamine.
AB  - Memantine and ketamine, voltage- and activation-dependent channel blockers of N
      methyl-d-aspartate (NMDA) receptors (NMDARs), have enjoyed a recent resurgence in
      clinical interest. Steady-state pharmacodynamic differences between these
      blockers have been reported, but it is unclear whether the compounds
      differentially affect dynamic physiologic signaling. In this study, we explored
      nonequilibrium conditions relevant to synaptic transmission in hippocampal
      networks in dissociated culture and hippocampal slices. Equimolar memantine and
      ketamine had indistinguishable effects on the following measures: steady-state
      NMDA currents, NMDAR excitatory postsynaptic current (EPSC) decay kinetics,
      progressive EPSC inhibition during repetitive stimulation, and extrasynaptic
      NMDAR inhibition. Therapeutic drug efficacy and tolerability of memantine have
      been attributed to fast kinetics and strong voltage dependence. However, pulse
      depolarization in drug presence revealed a surprisingly slow and similar time
      course of equilibration for the two compounds, although memantine produced a more
      prominent fast component (62% versus 48%) of re-equilibration. Simulations
      predicted that low gating efficacy underlies the slow voltage-dependent relief
      from block. This prediction was empirically supported by faster voltage-dependent
      blocker re-equilibration with several experimental manipulations of gating
      efficacy. Excitatory postsynaptic potential-like voltage commands produced drug
      differences only with large, prolonged depolarizations unlikely to be attained
      physiologically. In fact, we found no difference between drugs on measures of
      spontaneous network activity or acute effects on plasticity in hippocampal
      slices. Despite indistinguishable synaptic pharmacodynamics, ketamine provided
      significantly greater neuroprotection from damage induced by oxygen glucose
      deprivation, consistent with the idea that under extreme depolarizing conditions,
      the biophysical difference between drugs becomes detectable. We conclude that
      despite subtle differences in voltage dependence, during physiologic activity,
      blocker pharmacodynamics are largely indistinguishable and largely voltage
      independent. 

PMID- 24101303
TI  - Can posterior dynamic stabilization reduce the risk of adjacent segment
      deterioration?
AB  - AIM: The aim of this study was to systematically review the relevant literature
      to develop a benchmark for the incidence of adjacent segment degeneration (ASDeg)
      and adjacent segment disease (ASDis) following the posterior dynamic
      stabilization (PDS) procedure and to investigate whether conclusions can be made
      with regard to the isolated PDS procedure in reducing the risk of ASDeg and ASDis
      compared with fusion, and with regard to the role of additional PDS devices
      implanted adjacent to fusion in protecting from ASDeg and ASDis caused by the
      neighboring fusion. MATERIAL AND METHODS: We retrieved electronic databases of
      Medline, Ovid and Cochrane Central Registry of Controlled Trials, combined with a
      supplemental hand search. Thirty-one articles met our inclusion criteria.
      RESULTS: The pooled incidence of ASDeg and ASDis following PDS procedure was
      16.4% and 5.5% respectively. Data from comparative studies showed a significantly
      lower incidence of ASDeg and nonsignificantly lower incidence of ASDis following
      PDS than following fusion surgery. Further, the additional PDS devices implanted
      adjacent to fusion could significantly reduce the risk of ASDeg and
      nonsignificantly decrease that of ASDis caused by fusion. CONCLUSION: These
      results suggested relative success of the PDS procedure in protecting against
      ASDeg and ASDis.

PMID- 24101302
TI  - Multidrug-resistant bacteria in organ transplantation: an emerging threat with
      limited therapeutic options.
AB  - Multidrug-resistant organisms (MDROs) are an emerging threat in solid organ
      transplantation (SOT). The changing epidemiology of these MDROs is reviewed along
      with the growing evidence regarding risk factors and outcomes associated with
      both colonization and infection in SOT. The management of these infections is
      complicated by the lack of antimicrobial agents available to treat these
      infections, and only a handful of new agents, especially for the treatment of MDR
      GNR infections, are being evaluated in clinical trials. Due to the increased
      prevalence of MDROs and limited treatment options, as well as organ shortages,
      transplant candidacy and use of organs from donors with evidence of MDRO
      colonization and/or infection remain controversial. Increasing collaboration
      between transplant programs, individual practitioners, infection control
      programs, and researchers in antimicrobial development will be needed to face
      this challenge. 

PMID- 24101304
TI  - Further modified Taylor retractor for spinal surgery.
AB  - New techniques have minimized the incision length and thus required modifications
      of surgical instruments. The Taylor retractor is one of these instruments. We
      therefore designed several modifications of the classical Taylor retractor. The
      following structural modifications were made on the classical Taylor retractor:
      First, we provided detachable blades with three different lengths (60, 70, 80
      mm). Second, we breached a slit wide enough to let the intervertebral disc
      rongeurs to nestle down in it. Third, instead of a single sharp tip at the end of
      the blade, an arched blade that had two smooth tips was designed. Adjustable
      blades allowed placing the retractor just on the skin without any space between
      the retractor and skin by sliding the retractor over its blade downwards, thus
      providing a low-profile surgical retraction. The slit facilitated reaching the
      other side of the disc by leaning against the retractor. Pressing slightly and
      lowering the retractor subsided the skin and the paravertebral muscle,
      consequently facilitated motion of rongeurs and provided better exposure owing to
      low profile retraction. The arched blade with two tips served better placement
      with less traumatization at the facet joint. The relevant modifications
      facilitated the surgical procedure. We believe one retractor with adjustable
      blades is enough for more comfortable surgery at any depth. 

PMID- 24101305
TI  - Surgical treatment problems of hydrocephalus caused by spontaneus
      intraventricular hemorrhage in prematurely born children.
AB  - AIM: The aim of this study was to identify the most appropriate method of
      surgical treatment of hydrocephalus in preterm infants that is caused by
      spontaneous intraventricular hemorrhage (IVH) and to identify predictive factors
      of poor perioperative outcomes. MATERIAL AND METHODS: We present a series of 60
      patients with IVH and hydrocephalus, to whom a VP shunt or subcutaneous (Omaya)
      reservoir was placed, during the period from March 2006 to March 2011. RESULTS:
      Predictors of poor outcome with VP shunt placement were: gestational age
      (t=2.323, p=0.024), head circumference at birth (t=2.072, p=0.043), birth weight
      (t=2.832, p=0.006), Apgar score at birth (t=5.026, p < 0.01), number of days on
      assisted ventilation (Z=6.203, p < 0.001), peripartal asphyxia (chi < sup > 2 <
      /sup > =17.376, p < 0.01), respiratory distress (chi < sup > 2 < /sup > =9.176
      p=0.002). Predictors of poor outcome in getting Omaya reservoir are: low birth
      weight (t=2.560, p=0.016), low Apgar scores (t=3.059, p=0.005), an extended
      number of days on assisted ventilation (Z=4.404, p < 0.001), presence of
      peripartal asphyxia (chi2=9.977, p=0.002) and cardio-respiratory arrest
      (chi2=12.804, p < 0.001). CONCLUSION: The outcome of hydrocephalus caused by IVH
      in premature born children is the worst in perinatology. Our results suggest that
      the main predictive factor is preoperative condition of the child and that the VP
      shunt and Omaya reservoir are complementary methods of surgical treatment.

PMID- 24101306
TI  - Is intraoperative ultrasound required in cervical spinal tumors? A prospective
      study.
AB  - AIM: To determine the role of intraoperative ultrasonography (IOUSG) in the
      surgical management of patients with intradural spinal tumors. MATERIAL AND
      METHODS: Twenty-six patients with intradural spinal cord tumors were surgically
      treated under intraoperative ultrasonographic guidance between January 2007 and
      May 2011. Guidance with IOUSG was used in 26 patients, of which 14 fourteen had
      extramedullary and 12 had intramedullary tumors. Intraoperative ultrasound
      assistance was used to localize each tumor exactly before opening the dura. The
      extent of tumor resection was verified using axial and sagittal sonographic
      views. The extent of tumor resection achieved with IOUSG guidance was assessed on
      postoperative early control MRI sections. RESULTS: Total tumor resection was
      achieved in 22 (84%) of 26 cases. All of the residual tumors were typically
      intramedullary and infiltrative. The sensitivity of IOUSG for the determination
      of the extent of resection was found to be 92%. Ultrasonography was found to be
      effective in identification of tumor boundaries and protection of spinal cord
      vessels. The average time spent for IOUSG assessment was 7 minutes. CONCLUSION:
      Intraoperative ultrasonography is practical, reliable and highly sensitive for
      spinal cord surgery. It not only enhances surgical orientation, but also reduces
      morbidity and helps to resect the tumor completely.

PMID- 24101307
TI  - Hyperbaric oxygen in epidural fibrosis: is there a potential for treatment?
AB  - AIM: To investigate the effects of hyperbaric oxygen treatment on epidural
      fibrosis formation in an experimental laminectomy model. MATERIAL AND METHODS:
      Twenty-four Wistar rats underwent L5-L6 total laminectomy and divided into three
      groups. Animals in the control group received no further treatment while animals
      in short and long term groups received 2,5 ATM ABS of hyperbaric oxygen for 3 and
      7 days, respectively. The amount of epidural fibrosis was analyzed histologically
      at the end of 42 days of follow up. RESULTS: The ratio of severe fibrosis was 57%
      in the control, 29% in the short HBOT, and 14% in the long HBOT groups. Although
      there was a clear trend towards having less fibrosis in the HBOT groups, the
      difference did not reach to the level of statistical significance (p=0.242),
      probably due to small number of animals used in this preliminary study.
      CONCLUSION: Our findings suggest that hyperbaric oxygen treatment may have
      favorable effects on epidural fibrosis. Further studies with larger cohorts are
      required to prove our results.

PMID- 24101308
TI  - Diagnosis and management of pituitary abscess: a case series and review of the
      literature.
AB  - AIM: Pituitary abscess is a disorder characterized with central nervous system
      (CNS) infection, mass effect, and endocrine dysfunction. These abscesses
      generally occur due to hematogenous spread in conditions such as paranasal
      sinusitis, sepsis, and where the blood brain barrier breaks down. This paper aims
      to discuss four cases of preoperatively diagnosed pituitary abscess in the light
      of the literature. MATERIAL AND METHODS: Following detailed clinical and hormonal
      examinations and imaging tests, 210 cases of pituitary adenoma and other sellar
      pathologies were operated on at the Neurosurgery clinic of Goztepe Training and
      Research Hospital. RESULTS: All the patients showed fever, systemic signs of
      toxemia and endocrine dysfunction at the time of diagnosis. In these cases, a
      preoperative diagnosis of the disease was made thanks to characteristic MRI
      findings. The four cases were operated by the transnasal transsphenoidal approach
      and histopathological and microbiological studies were performed for surgical
      specimens. CONCLUSION: Pituitary abscesses are rare disorders responsible for a
      high mortality risk. Mortality and morbidity can be reduced by early surgical
      drainage and appropriate antibiotic treatments. Additionally, these cases should
      be closely followed-up in terms of pituitary insufficiency, surgical
      complications and infection.

PMID- 24101309
TI  - The effects of levetiracetam on neural tube development in the early stage of
      chick embryos.
AB  - AIM: This study aimed to investigate the effects of a new generation
      antiepileptic agent, levetiracetam, on the neural tube development in a chick
      embryo model that corresponds to the first month of vertebral development in
      mammals. MATERIAL AND METHODS: Forty-five Atabey(r) breed fertilized chicken eggs
      with no specific pathogens were randomly divided into 5 groups. All of the eggs
      were incubated at 37.8+/-2 degrees C and 60+/-5 % relative humidity in an
      incubator. Group A was control group. The other eggs were applied physiological
      saline and drugs at a volume of 10 MUL by the in ovo method at the 28th hour of
      the incubation period. Group B was given distilled water; Group C, physiological
      saline; Group D, Levetiracetam (L8668) at a dose equivalent to the treatment dose
      for humans (10 mg/ kg), and Group E, Levetiracetam (L8668) at a dose of 10 times
      the treatment dose. The embryos in all of the groups were removed from the shells
      at the 48th hour and morphologically and histologically evaluated. RESULTS: Of
      the 45 embryos incubated, neural tubes of 41 were closed and the embryos
      displayed normal development. CONCLUSION: Levetiracetam, at a dose equivalent to
      human treatment dose and 10 times the treatment dose, was shown not to cause
      neural tube defects in chick embryos.

PMID- 24101310
TI  - Comparison of the effects of local and systemic dexamethasone on the rat
      traumatic sciatic nerve model.
AB  - AIM: The aim of the study was to evaluate the effect of peroperatively locally
      administered dexamethasone on nerve recovery after induced nerve crush injury.
      MATERIAL AND METHODS: 4 groups of 8 animals were formed. The sciatic nerves of 32
      rats were exposed at midthigh level and those of 24 rats were crushed for 30
      seconds with a pair of jeweler's forceps. RESULTS: Sciatic functional index (SFI)
      measurements of all the animals included at days 7, 14, 21 and 28 was
      statistically significant (p < 0.05). Pinch tests that were done on the first 13
      days gave negative results in all the groups. There was a difference between the
      test results of Group II and those of Group III and IV at days 14, 21 and 28.
      When the duration of the experiment was taken as a whole, no difference was
      observed between the test results of Group III and IV. CONCLUSION: Recovery in
      the group treated with local dexamethasone was more remarkable than that in the
      group treated with systemic dexamethasone in our study. As the difference was
      statistically significant, we recommend the perioperative use of local
      dexamethasone in procedures that might induce nerve injury.

PMID- 24101311
TI  - Hemilaminectomy approach combined with in situ restoration of vertebral laminae
      for thoracic intraspinal tumors.
AB  - AIM: This study aims to evaluate the hemilaminectomy approach and in situ
      restoration of vertebral laminae in microsurgery for thoracic intraspinal tumors.
      MATERIAL AND METHODS: Sixteen patients with thoracic intraspinal tumors,
      consisting of 6 males and 10 females with a mean age of 47.5+/-16.4 years ranging
      from 21 to 71 years, underwent surgical treatment with hemilaminectomy approach
      and in situ restoration of vertebral laminae. All patients were followed up after
      surgery for 12 to 30 months, involving Frankel grade, spinal instability, and
      deformity. RESULTS: Mean operation time was 119.5+/-23.0 minutes. Laminotomy was
      performed with one vertebral plate in 2 cases, two vertebral plates in 12 cases,
      and three vertebral plates in 2 cases. Postoperative three-dimensional CT
      scanning revealed a stable bony reconstruction, and no cerebrospinal fluid
      leakage or subcutaneous hydrops. Surgical pathology was consistent with
      preoperative MRI diagnosis. With respect to neurological status, the percentage
      of good Frankel scale was markedly improved from 37.5% on admission to 81.3% at
      follow-up (p < 0.05). None of the subjects showed spinal deformity or
      instability. CONCLUSION: In situ restoration of vertebral laminae maximally
      preserves the spinal integrity and stability, and reduces postoperative
      complications including cerebrospinal fluid leakage, pseudomeningocele, spinal
      deformity, and instability.

PMID- 24101312
TI  - A new guide tube for odontoid screw fixation for unstable odontoid fractures:
      report of 6 case series.
AB  - AIM: We describe a modified form of traditional open surgery with a new guide
      tube. This guide tube permits anterior screwing of odontoid in a shorter time
      with a more simple technique as compared to traditional open surgery, endoscopic
      and percutaneous surgeries. MATERIAL AND METHODS: Our series includes 6 patients
      who were operated for unstable odontoid fracture. We used a new guide tube for
      anterior odontoid screw fixation. This guide tube was designed by the first
      author to facilitate the insertion of the K-wire for placement of a cannulated
      lag screw. RESULTS: Successful placement of the odontoid screws and immediate
      spinal stabilization were achieved in all patients. Solid fusion was observed
      during follow-up time in all patients. CONCLUSION: This screw insertion technique
      for odontoid screw fixation provides a minimally invasive, safe and easy surgery
      in contrast to other surgical approaches.

PMID- 24101313
TI  - Analysis of risk factors for recurrence of giant cell tumor of the sacrum and
      mobile spine combined with preoperative embolization.
AB  - AIM: To investigate the factors related to the local recurrence-free survival
      time (LRFS) after surgical treatment of GCT of the sacrum and mobile spine
      combined with preoperative embolization. MATERIAL AND METHODS: We retrospectively
      reviewed 28 consecutive patients with GCT of the sacrum and mobile spine who
      underwent initial surgical excision combined with preoperative embolization
      between 1995 and 2011. Data regarding age, gender, tumor location, tumor size,
      tumor extension, radiation therapy, and local recurrences were reviewed and
      analyzed statistically. RESULTS: All patients underwent intralesional resection.
      The average duration of follow-up was 86.4 months (range, 15 - 193 months). 8
      (28.6%) patients developed local recurrence. The average recurrence time was 35.6
      months (range, 5 - 79 months), and the local recurrence-free survival rates at 3
      and 5 years were 89.1% and 75.5%, respectively. LRFS was found statistically
      longer in intracompartmental (T1) tumors as compared with extracompartmental (T2)
      tumors (P < 0.05), but not for age, gender, tumor location, tumor size, or
      radiation therapy. CONCLUSION: Intralesional excision with preoperative
      embolization is a feasible choice for T1 tumors of the sacrum and mobile spine,
      but for T2 tumors, more aggressive treatment may be required. The choice of
      surgical treatment should be balanced between the complications and tumor
      recurrence.

PMID- 24101314
TI  - Clinical characteristics and outcomes of patients with cerebral herniation during
      continuous lumbar drainage.
AB  - AIM: The aim of this study was to investigate the clinical characteristics and
      outcomes of patients who developed cerebral herniation after continuous lumbar
      cerebrospinal fluid (CSF) drainage. MATERIAL AND METHODS: We retrospectively
      reviewed eight patients who developed cerebral herniation after receiving
      continuous lumbar drainage between January 2009 and March 2012 in our department.
      RESULTS: All eight patients were male, aged from 21 to 66 years old. All eight
      patients received surgical treatment and exhibited impaired consciousness before
      lumbar drainage, and five (62.5%) also underwent decompressive craniectomy. The
      average drainage speed in these patients varied from 8.3 mL/h to 20.0 mL/h,
      demonstrating an inverse correlation with the latency period of brain herniation
      after initiation of the drainage (p=0.017). Four (50.0%) patients experienced
      cardiopulmonary instability at the onset of cerebral herniation, requiring
      immediate resuscitation. After drainage clamping and supportive treatment, seven
      (87.5%) patients displayed complete reversal of cerebral herniation within 48 h.
      CONCLUSION: Cerebral herniation induced by continuous lumbar drainage is mostly
      reversible if early identification and prompt management are realized. Faster
      drainage speed may be associated with earlier occurrence of brain herniation
      during lumbar drainage.

PMID- 24101315
TI  - Does probe's eye subthalamic nucleus length on T2W MRI correspond with
      microelectrode recording in patients with deep brain stimulation for advanced
      Parkinson's disease?
AB  - AIM: Subthalamic nucleus (STN) deep brain stimulation (DBS) has become a well
      accepted treatment for patients with advanced Parkinson's disease (PD). During
      surgical planning for DBS, the length of the STN is taken into account and
      verified during microelectrode recording (MER) intraoperatively. Here, we
      addressed the question to which extent the length of the STN measured with the T2
      weighted MRI in the probe's eye view corresponded with the intraoperatively
      determined length of the STN with MER. MATERIAL AND METHODS: We included 10
      consecutive Parkinson's disease patients who underwent STN DBS surgery. The
      length of the STN in the probe's eye view mode was calculated along the
      trajectory of the central MER electrode crossing the STN. RESULTS: Our analysis
      showed no statistical difference between the length of the STN measured with the
      T2 weighted probe's eye view mode and the MER (right STN length 5.8 +/- 0.9 mm
      MRI vs. 6.3 +/- 0.5 mm MER, p > 0.05; left STN length 5.6 +/- 0.4 mm MRI vs 5.8
      +/- 1 mm MER, p > 0.05). CONCLUSION: This means that the entry and the exit of
      the STN can be adequately estimated using the probe's eye view preoperatively.

PMID- 24101316
TI  - Neuroprotective effect of magnesium sulfate and dexamethasone on intrauterine
      ischemia in the fetal rat brain: ultrastructural evaluation.
AB  - AIM: The aim of this study was to investigate the neuroprotective effect of
      magnesium sulfate and dexamethasone on oxidative damage in intrauterine ischemia.
      MATERIAL AND METHODS: In this study, 19-day pregnant rats were divided into five
      groups. Fetal brain ischemia was achieved in the ischemia/ reperfusion (I/R)
      group by bilaterally closing the utero-ovarian artery with aneurysm clips for 30
      min and subsequently removing the aneurysm clips for 60 min for reperfusion. Mg
      (600 mg/kg) and dexamethasone (0.25 mg/kg) were administered 20 min before the
      I/R insult. The lipid peroxidation in the brain tissue was determined by the
      concentration of thiobarbituric acid reactive substances (TBARS). The
      mitochondrial score was calculated after an evaluation with electron microscopy.
      RESULTS: Both the electron microscope and TBARS data showed a significant
      difference between the control and I/R groups. The Mg and dexamethasone treatment
      groups exhibited significantly lower TBARS values compared to the IR group.
      Similarly, the mitochondrial scores in the Mg and dexamethasone treatment groups
      were significantly lower than those in the I/R group. CONCLUSION: Result showed
      that magnesium sulfate and dexamethasone prevent lipid peroxidation and reduce
      mitochondrial injury thus suggests neuroprotective effects in fetal rat brain in
      intrauterine ischemia-reperfusion (I/R) injury.

PMID- 24101317
TI  - Hemangioblastoma of the filum terminale associated with von Hippel-Lindau
      disease: a case report.
AB  - We report a 41-year-old man who presented with low back pain, lower extremity
      paresthesia, urinary retention and constipation. Magnetic resonance imaging
      showed a vascular intradural-extramedullary lesion at the second lumbar vertebral
      level. His medical history revealed that he had undergone surgery for a
      cerebellar hemangioblastoma 5 years ago. The patient underwent a spinal operation
      and a vascular tumor was removed from filum terminale. Pathologic examination of
      the tumor revealed a hemangioblastoma. Hemangioblastomas may occur sporadically
      or in association with von Hippel-Lindau disease. In the second case, they are
      often multiple and accompanied by cerebellar and brainstem lesions. The
      hemangioblastomas reported in the conus medullaris or in the extramedullary
      compartment adjacent to the conus medullaris are rare, tumors of the cauda equina
      are uncommon, and lesions of the filum terminale are extremely rare. We report a
      patient with von Hippel-Lindau disease having filum terminale hemangioblastoma
      and discuss the diagnosis, pathogenesis and treatment of hemangioblastoma. 

PMID- 24101318
TI  - Intra-arterial injection of indocyanine green in cerebral arteriovenous
      malformation surgery.
AB  - Surgical microscope-integrated intraoperative angiography with intra-venous
      injection of indocyanine green (ICG) has been widely used during bypass or
      aneurysm surgery. Instead of intra-venous injection of ICG, we describe a case of
      intraoperative video angiography with intra-arterial injection of ICG in cerebral
      arteriovenous malformation (AVM) surgery. During the surgery, we injected ICG
      through a catheter placed in the internal carotid artery in each step. The
      technique was feasible and useful to distinguish feeders from normal arteries and
      to observe changes in flow dynamics. Intra-arterial injection of ICG had better
      phase contrast than intra-venous injection of ICG and better spatial resolution
      than digital subtraction angiography. Therefore, this technique can be helpful in
      cerebral AVM surgery. 

PMID- 24101319
TI  - Surgical management of symptomatic T8 vertebral hemangioma: case report and
      review of the literature.
AB  - Vertebral hemangiomas are benign vascular lesions of the vertebral column; only
      0.9-1.2% of all vertebral hemangiomas cause spinal cord compression. We report a
      34-year-old female who was admitted to the neurosurgery clinic with a history of
      back pain, poor quality of life and easy fatigability for 1.5 years. Her medical
      history revealed a fall from a height of 2 meters 1.5 years ago. Neurology
      examination revealed bilateral hypoesthesia below the T8 level and hyperactive
      deep tendon reflexes in her left leg. Computed tomography scan of the thoracic
      spine showed T8 vertebral hemangioma, and magnetic resonance imaging showed a T8
      hemangioma compressing the spinal cord. Surgical intervention was planned and T8
      total laminectomy was performed. The tumor extending into the anterior spinal
      cord was resected, and T8 vertebroplasty with short segment posterior
      stabilization and fusion was performed. We aimed to present a new treatment
      approach for symptomatic vertebral hemangiomas and reviewed the relevant
      literature. 

PMID- 24101320
TI  - Coexistence of trifid and bifid median nerve in a patient with bilateral carpal
      tunnel syndrome.
AB  - Carpal tunnel syndrome is the most common upper extremity neuropathy in the wrist
      that may be associated with anatomic variations of median nerve. Trifurcation of
      the median nerve has been very rarely reported in the literature. We report
      coexistence of bilateral median nerve variation in the wrist and its radiological
      features. Ultrasonography and magnetic resonance imaging was performed to the
      patient after Tinel and Phalen tests. There was bifurcation and trifurcation of
      the median nerve in right and left wrists respectively. Bilateral carpal tunnel
      syndrome was caused by bilateral median nerve variation in the present case. When
      a median nerve variation is detected in one wrist, a possible variation at the
      other side should be kept in mind and hence should be evaluated. A thorough
      knowledge of the variations of the median nerve is essential in order to avoid
      surgical complications and to ensure optimal patient outcome. US is an easy and
      cheap radiological method for diagnosis and it should be the first chosen
      radiological technique to evaluate median nerve variations in idiopathic CTS
      patients. 

PMID- 24101321
TI  - A case of vocal cord paralysis secondary to vertebral artery dolichoectesia: a
      rare presentation.

PMID- 24101322
TI  - Virtual reality implementation in neurosurgical practice: the "can't take my eyes
      off you" effect.
AB  - During the last few years, virtual reality (VR) has been increasingly implemented
      in the neurosurgical practice. The scope of this paper is to briefly outline the
      educational role of this novel technology in training surgeons. At the same time,
      the ability of VR workstations such as the Dextroscope(r) to consistently
      simulate the surgical trajectory to the lesion-target is highlighted. The authors
      shed light to the current applications of VR systems in the neurosurgical field
      by describing not only the advantages of those systems, but their principal
      drawbacks as well. It seems that VR has come to stay and it is already the new
      best friend of residents due to its "Can't take my eyes off you effect". 

PMID- 24101323
TI  - Management of brain abscess.

PMID- 24101333
TI  - A fair comparison should be based on the same protocol--comments on "trainable
      convolution filters and their application to face recognition".
AB  - We comment on a paper describing an image classification approach called Volterra
      kernel classifier, which was called Volterrafaces when applied to face
      recognition. The performances were evaluated by the experiments on face
      recognition databases. We find that their comparisons with the state of the art
      of three databases were indeed based on unfair settings. The results with the
      settings of the standard protocol on three data sets are generated, which show
      that Volterrafaces achieves the state-of-the-art performance only in one
      database.

PMID- 24101324
TI  - A phase 2 study of everolimus combined with trastuzumab and paclitaxel in
      patients with HER2-overexpressing advanced breast cancer that progressed during
      prior trastuzumab and taxane therapy.
AB  - Increased activation of the PI3K/Akt/mTOR pathway is a common factor in putative
      mechanisms of trastuzumab resistance, resulting in dysregulation of cell
      migration, growth, proliferation, and survival. Data from preclinical and phase
      1/2 clinical studies suggest that adding everolimus (an oral mTOR inhibitor) to
      trastuzumab plus chemotherapy may enhance the efficacy of, and restore
      sensitivity to, trastuzumab-based therapy. In this phase 2 multicenter study,
      adult patients with HER2-positive advanced breast cancer resistant to trastuzumab
      and pretreated with a taxane received everolimus 10 mg/day in combination with
      paclitaxel (80 mg/m(2) days 1, 8, and 15 every 4 weeks) and trastuzumab (4 mg/kg
      loading dose followed by 2 mg/kg weekly), administered in 28-day cycles.
      Endpoints included overall response rate (ORR), progression-free survival (PFS),
      overall survival (OS), and safety. Fifty-five patients were enrolled; one
      remained on study treatment at the time of data cutoff. The median number of
      prior chemotherapy lines for advanced disease was 3.5 (range 1-11). The ORR was
      21.8 %, the clinical benefit rate was 36.4 %, the median PFS estimate was 5.5
      months (95 % confidence interval [CI]: 4.99-7.69 months), and the median OS
      estimate was 18.1 months (95 % CI: 12.85-24.11 months). Hematologic grade 3/4
      adverse events (AEs) included neutropenia (25.5 % grade 3, 3.6 % grade 4), anemia
      (7.3 % grade 3), and thrombocytopenia (5.5 % grade 3, 1.8 % grade 4).
      Nonhematologic grade 3/4 AEs included stomatitis (20.0 %), diarrhea (5.5 %),
      vomiting (5.5 %), fatigue (5.5 %), and pneumonia (5.5 %), all grade 3. These
      findings suggest that the combination of everolimus plus trastuzumab and
      paclitaxel is feasible, with promising activity in patients with highly resistant
      HER2-positive advanced breast cancer. This combination is currently under
      investigation in the BOLERO-1 phase 3 trial. 

PMID- 24101336
TI  - Recombinant human soluble thrombomodulin is active against hemophagocytic
      lymphohistiocytosis associated with acquired immunodeficiency syndrome.
AB  - A 39-year-old man was admitted to our hospital to initiate highly active anti
      retroviral therapy (HAART) for documented acquired immune deficiency syndrome.
      The HIV load was 2.5 million copies/mL and the CD4-positive lymphocyte count was
      only 52 cells/uL at presentation. The HAART regimen consisted of lamivudine and
      abacavir as the backbone, plus raltegravir and lopinavir/ritonavir as the base.
      The day after initiating HAART, his body temperature rose to 102.4  degrees F
      (39.1  degrees C), accompanied by elevated levels of liver enzymes, neutropenia,
      coagulopathies, and an extremely high serum ferritin level, prompting us to
      suspect hemophagocytic lymphohistiocytosis (HLH) and disseminated intravascular
      coagulation (DIC). To correct the coagulation abnormalities, recombinant
      thrombomodulin (rTM) was initiated at 375 U/kg. Surprisingly, fever resolved
      almost immediately, in parallel with dramatic decreases in serum levels of
      ferritin and liver enzymes and prompt normalization of coagulopathy with only two
      doses of rTM. The patient subsequently developed amebiasis, which was
      successfully treated using metronidazole. In summary, the use of rTM dramatically
      improved not only DIC, but also HLH, suggesting potent anti-inflammatory effects
      of the agent. Although further clinical reports and trials are needed, rTM
      appears to provide an additional therapeutic option in the management of HLH.

PMID- 24101342
TI  - Sequence analysis of shorter than genome length episomal Banana streak OL virus
      like sequences isolated from banana in India.
AB  - Electron microscopy and sequencing of reverse transcriptase and ribonuclease H
      (RT/RNase H) region of Badnavirus genome from two banana cultivars: Poovan
      (triploid: AAB) and Safed velchi (diploid: AB), exhibiting leaf streak symptoms,
      confirmed the association of Banana streak OL virus (BSOLV). As per ICTV species
      demarcation threshold of 80 % identity in RT/RNase H region, both the isolates
      were identified as BSOLV. Rolling circle and end-to-end amplification showed the
      association of two short episomal BSOLV variants: BSOLV-IN1 and BSOLV-IN2 from
      Poovan and Safed velchi banana, respectively. The genome sizes of both isolates
      were 6,950 nucleotides long, but shorter than the typical BSOLV genome of 7,389
      bp. Open reading frames (ORFs) 1 and 2 of shorter BSOLV isolates shared almost
      complete nucleotide identity (>99 %) to that of BSOLV. However, the ORF 3 (5,130
      bp) and intergenic region (IGR), 886 bp, showed deletions compared with ORF 3
      (5,499 bp) and IGR (956 bp) of BSOLV. In phylogenetic analysis for ORF 3
      polyprotein, both the isolates clustered with BSOLV, Banana streak CA virus
      (BSCAV), and Sugarcane bacilliform GA virus (SCBGAV). Identical ORF 1, ORF 2, and
      the presence of all the conserved domains in short ORF 3 and promoter elements in
      IGR indicated that these isolates represent replicationally competent shorter
      variants of BSOLV. These two shorter-than-BSOLV genome sequences and two other
      identical banana streak virus sequences in GenBank (BSV-TRY; DQ859899 and BSV-GD;
      DQ451009) might have evolved due to error-prone reverse transcription and
      splicing or excision from the integrated sequences by homologous recombination in
      natural banana hybrids under field conditions.

PMID- 24101343
TI  - Using ambiguous plaid stimuli to investigate the influence of immediate prior
      experience on perception.
AB  - In a series of three experiments, we used an ambiguous plaid motion stimulus to
      explore the behavioral and electrophysiological effects of prior stimulus
      exposures and perceptual states on current awareness. The results showed that
      prior exposure to a stimulus biased toward one percept led to subsequent
      suppression of that percept. In contrast, in the absence of stimulus bias, prior
      perceptual experience can have a facilitative influence. The suppressive effects
      caused by the prior stimulus were found to transfer to an ambiguous plaid test
      stimulus rotated 180o relative to the adaptation stimulus, but were abolished if
      (1) the ambiguous test stimulus was only rotated 90o relative to the adaptation
      stimulus or (2) the adaptation stimulus was heavily biased toward the component
      grating percept. Event-related potential recordings were consistent with the
      involvement of visual cortical areas and suggested that the influence of recent
      stimulus exposure may involve recruitment of additional brain processes beyond
      those responsible for initial stimulus encoding. In contrast, the effects of
      prior and current perceptual experience appeared to depend on similar brain
      processes. Although the data presented here focus on vision, the work is
      discussed within the context of data from a parallel series of experiments in
      audition. 

PMID- 24101341
TI  - Genetic characterization of canine influenza A virus (H3N2) in Thailand.
AB  - In January 2012, several clinical cases of dogs with flu-like symptoms, including
      coughing, sneezing, nasal discharge, and fever, were reported in a small-animal
      hospital located in Bangkok, Thailand. One influenza A virus was identified and
      characterized as an avian-like influenza virus H3N2. The virus was named
      A/canine/Thailand/CU-DC5299/12. A phylogenetic analysis indicated that the canine
      virus belonged to an avian Eurasian lineage and was genetically related to the
      canine influenza viruses H3N2 from China and Korea. This canine virus displays a
      unique genetic signature with two amino acid insertions in the NA protein, which
      is similar to the canine influenza viruses from eastern China (Zhejiang and
      Jiangsu). This study constitutes the first report of H3N2 canine influenza virus
      infection in a small-animal hospital in Thailand. 

PMID- 24101344
TI  - What skilled typists don't know about the QWERTY keyboard.
AB  - We conducted four experiments to investigate skilled typists' explicit knowledge
      of the locations of keys on the QWERTY keyboard, with three procedures: free
      recall (Exp. 1), cued recall (Exp. 2), and recognition (Exp. 3). We found that
      skilled typists' explicit knowledge of key locations is incomplete and
      inaccurate. The findings are consistent with theories of skilled performance and
      automaticity that associate implicit knowledge with skilled performance and
      explicit knowledge with novice performance. In Experiment 4, we investigated
      whether novice typists acquire more complete explicit knowledge of key locations
      when learning to touch-type. We had skilled QWERTY typists complete a Dvorak
      touch-typing tutorial. We then tested their explicit knowledge of the Dvorak and
      QWERTY key locations with the free recall task. We found no difference in
      explicit knowledge of the two keyboards, suggesting that typists know little
      about key locations on the keyboard, whether they are exposed to the keyboard for
      2 h or 12 years. 

PMID- 24101345
TI  - Testing for controlled variables: a model-based approach to determining the
      perceptual basis of behavior.
AB  - Perceptual control theory (PCT) views behavior as being organized around the
      control of perceptual variables. Thus, from a PCT perspective, understanding
      behavior is largely a matter of determining the perceptions that organisms
      control-the perceptions that are the basis of the observed behavior. This task is
      complicated by the fact that very often the perceptions that seem to be the
      obvious basis of some behavior are not. This problem is illustrated using a
      simple pursuit-tracking task in which the goal was to keep a cursor vertically
      aligned with a target set at various horizontal distances from the cursor. The
      "obvious" perceptual basis of the behavior in this task is the vertical distance
      between cursor and target. But a control model suggests that a better description
      of the perceptual basis of the behavior is the angle between cursor and target.
      The experiment shows how a control model can be used to do the test for the
      controlled variable, a control-theory-based approach to distinguishing the actual
      from the apparent perceptual basis of any behavior. 

PMID- 24101348
TI  - Decompressive craniectomy for management of traumatic brain injury: an update.
AB  - Decompressive craniectomy (DC) for the management of severe traumatic brain
      injury (TBI) has a long history but remains controversial. Although DC has been
      shown to improve both survival and functional outcome in patients with malignant
      cerebral infarctions, evidence of benefit in patients with TBI is decidedly more
      mixed. Craniectomy can clearly be life-saving in the presence of medically
      intractable elevations of intracranial pressure. Craniectomy also has been
      consistently demonstrated to reduce "therapeutic intensity" in the ICU, to reduce
      the need for intracranial-pressure-directed and brain-oxygen-directed
      interventions, and to reduce ICU length of stay. Still, the only randomized trial
      of DC in TBI failed to demonstrate any benefit. Studies of therapies for TBI,
      including hemicraniectomy, are challenging owing to the inherent heterogeneity in
      the pathophysiology observed in this disease. Craniectomy can be life-saving for
      patients with severe TBI, but many questions remain regarding its ideal
      application, and the outcome remains highly correlated with the severity of the
      initial injury.

PMID- 24101349
TI  - Experiences of work and sickness absence in employees with depression: an
      interpretative phenomenological analysis.
AB  - PURPOSE: The experience of employment with depression is explored to develop
      understanding of the mediators that may influence the management of depression
      related sickness absence and improve theoretical understanding. METHOD: Data were
      collected from seven semi-structured interviews and Interpretative
      Phenomenological Analysis used to explore the data. RESULTS: Three interrelated
      themes were drawn from the participants' accounts: (1) the interaction between
      depression and work; (2) illness beliefs; and (3) organisational context and
      depression. The analysis revealed that participants appeared to hold five key
      perceptions about their depression and work: low control in the workplace; lack
      of line manager support; diminishing ability to work; the need to address
      depressive symptoms; and perceptions of depression. Their strength resulted in
      individuals reaching sickness absence thresholds. The themes and participants'
      accounts of their work and sickness absence and return to work behaviour are
      discussed in relation to relevant theory and evidence to understand how these
      perceptions and beliefs mediate behaviour. CONCLUSION: Individuals' health
      (illness representations) and work beliefs (outcome expectancies and self
      efficacy for work tasks and management of health at work) appear to influence
      individuals' sickness absence decisions and experiences and these are mediated by
      individuals' experiences of organisational policies, line manager support and the
      messages and actions of GPs.

PMID- 24101350
TI  - Squamous cell carcinoma of lung with osteo-cartilaginous metaplasia - a case
      report and review of the literature.
AB  - Calcification and ossification are very rare in primary squamous cell carcinoma
      of the lung. We report a 55-year-old male with primary squamous cell carcinoma of
      the lung who on histopathological examination was seen to have extensive
      calcification and ossification. Squamous carcinoma of the lung rarely presents
      with osteocartilaginous metaplasia. The case is presented here for its unique
      presentation. 

PMID- 24101351
TI  - [Pemphigoid gestationis: light microscopic and direct immunofluorescense
      findings].
AB  - Pemphigoid gestationis is a rare vesiculobullous dermatosis of pregnancy and
      puerperium. It is commonly seen in second or third trimester. Skin lesions are
      characterized by pruritic, urticarial plaques with the development of tense
      vesicles and bullae. Histopathology demonstrates a subepidermal eosinophil-rich
      vesiculation. Direct immunofluorescence microscopy reveals linear complement 3
      and immunoglobulin G deposition along the basement membrane. We present a rare
      case of pemphigoid gestationis occurring in a 33-year-old pregnancy woman with
      symptom of generalized pruritis. Pemphigoid gestationis should be kept in mind in
      the differential diagnosis of vesiculobullous dermatitis of pregnancy. 

PMID- 24101352
TI  - Soft tissue giant cell tumor of low malignant potential of the neck: a case
      report and review of the literature.
AB  - Giant cell tumor of soft parts is a rare tumor that is clinically and
      histologically similar to giant cell tumor of the bone. We present a 53-year-old
      female with a giant cell tumor of low malignant potential arising from the neck.
      The clinicopathological features and the importance of immunohistochemistry in
      the differential diagnosis with other giant cell rich tumors was discussed. 

PMID- 24101353
TI  - Tumor-like cystic endosalpingiosis in the myometrium: a case report and a review
      of the literature.
AB  - Endosalpingiosis is a disorder of the Mullerian system characterized by benign
      glands lined with tubal type epithelium and involves the peritoneum,
      subperitoneal tissues and retroperitoneal lymph nodes. Myometrial
      endosalpingiosis is very rare. A 44-year-old female presented to the hospital
      complaining of menorrhagia. Gynecological and radiologic examination revealed a
      pelvic mass 7.5 cm in diameter, suggestive of a leiomyoma with secondary cystic
      changes. The gross examination showed an intramural large cyst within the right
      fundic wall of the uterus. Microscopically, the cyst consisted of multiple micro
      macro cysts lined with benign tubal epithelium. With these findings, the
      diagnosis was cystic endosalpingiosis. In this report, the clinicopathologic
      features of a cystic endosalpingiosis case located in the myometrium was
      presented with a review of the literature. 

PMID- 24101354
TI  - Cytohistopathological correlation of a case of squamous cell carcinoma of
      gallbladder with lymph node metastasis.
AB  - Primary carcinomas of the gallbladder are rare malignancies and adenocarcinoma is
      the more common subtype. Primary squamous cell carcinoma of the gallbladder has
      rarely been diagnosed by aspiration cytology. Here, we present a case of a 62
      year old female patient suffering from abdominal complaints who underwent
      ultrasound-guided fine-needle aspiration cytology and was diagnosed as
      keratinizing squamous cell carcinoma of gallbladder. The diagnosis was confirmed
      on subsequent histopathological examination that also revealed metastasis in the
      cystic lymph node. Histogenesis and biological behavior of squamous cell
      carcinoma of gallbladder remains a matter of debate but the role of aspiration
      cytology in diagnosing these lesions cannot be undermined. 

PMID- 24101355
TI  - Pulmonary lymphangioleiomyomatosis: a rare case.
AB  - Lymphangioleiomyomatosis is an uncommon lung disease primarily affecting women of
      childbearing age. It is characterized by the progressive proliferation and
      infiltration of smooth muscle-like cells, which lead to cystic destruction of the
      lung parenchyma; obstruction of airways, blood vessels, and lymphatics; and loss
      of pulmonary function. We present the case of a 46-year-old female patient with
      chest pain, cough, sputum, and dyspnea on exertion for three weeks. Minimal
      pneumothorax was noted, and the patient was referred to our center for further
      investigation and treatment. High-resolution computed tomography revealed
      numerous bilateral thin-walled air cysts and interstitial thickening affecting
      the central and peripheral part of the upper zone of the lung. We performed an
      open-lung biopsy to confirm lymphangioleiomyomatosis. Our aim is to discuss the
      pathogenesis and other lesions noted in the differential diagnosis of this rare
      disease. 

PMID- 24101356
TI  - Pleuropulmonary Blastoma: A Case Report.
AB  - Pleuropulmonary blastoma is rare embryonal tumor of infancy and early childhood
      and it often arises from lung and more rarely from the parietal pleura. We
      present this entity which has no systematic data associated with its incidence in
      order to discuss clinical, histopathological, immunohistochemical features and
      the differential diagnosis. A three-year-old boy presented with fever showed
      signs of upper respiratory tract infection. Radiological examination revealed a
      solid mass filling the right hemithorax. The patient underwent core needle
      biopsy, wedge biopsy and lobectomy. Biopsy and surgical material were examined
      histopathologically. The tumor was composed of predominantly solid areas
      consisting blastemal cells with spindle, polygonal and round nuclei in the myxoid
      stroma. Immunohistochemical staining of the tumor cells were positive with
      vimentin and desmin. MIB-1 labeling index was above 90%. Histological diagnosis
      was pleuropulmonary blastoma type 3. The surgically sampled adjacent diafragma
      was also infiltrated with the tumor. The patient was treated with chemotherapy
      and showed no signs of recurrence in the follow-up of 9 months. Pleuropulmonary
      blastoma is a very rare childhood cancer that needs to be kept in mind in the
      pathological differential diagnosis of thoracic tumors in the children.

PMID- 24101357
TI  - Abnormal cervical cytology risk factors in the Western Black Sea Region and the
      importance of health insurance.
AB  - OBJECTIVE: To evaluate the prevalence of abnormal cervical cytological findings
      in the Western Black Sea Region and investigate an association between socio
      demographic risk factors and the presence of cytological abnormalities. MATERIAL
      AND METHOD: The reports of 11,539 cervical smears diagnosed according to Bethesda
      System 2001 version in the Pathology Department between January 2011 and December
      2012 were reviewed retrospectively from the hospital records and cytopathology
      reports. Repeated smear results, unsatisfactory smear results, patients with
      known gynecologic malignancy history, smear results of patients with hysterectomy
      and smear results of patients whose socio-demographic information could not be
      obtained were excluded from the evaluation. The results of 7,740 patients who met
      the criteria for the study were evaluated. RESULTS: The prevalence of cervical
      cytological abnormalities was 1.8 % in general. The prevalence rates for atypical
      squamous cells with undetermined significance (ASC-US), atypical squamous cells,
      cannot exclude a high-grade squamous intraepithelial lesion (ASC-H), low-grade
      squamous intraepithelial lesions (LSIL), high-grade squamous intraepithelial
      lesions (HSIL), and atypical glandular cells (AGC) were 1.16%, 0.11%, 0.29%,
      0.15%, and 0.03% respectively. The prevalence of cytologically diagnosed cervical
      invasive neoplasia was 0.025%. Advanced age, low education level (primary school
      or less) and not having health insurance were found as to be risk factors for
      preinvasive and invasive lesions. Women who had a high school education and
      previously had a smear test had decreased risk for developing preinvasive and
      invasive lesions. CONCLUSION: This study shows prevalence of abnormal cervical
      cytology findings and associated risk factors in the Western Black Sea Region of
      Turkey. The most important risk factor was identified as not having health
      insurance.

PMID- 24101358
TI  - Solid pseudopapillary neoplasm of the pancreas: report of a rare case and review
      of the literature.
AB  - Solid pseudopapillary neoplasm, a rare primary neoplasm of the pancreas that
      typically affects young women, is a relatively indolent entity with favorable
      prognosis. We here report a 20-year-old young girl with solid pseudopapillary
      neoplasm who presented with mild dull abdominal discomfort without any
      significant laboratory findings. On MRI, a heterogenous mass was found at the
      distal pancreas. The patient underwent en-block distal pancreatectomy with
      splenectomy with the presumptive diagnosis of cystic neoplasm of the pancreas.
      The tumor was well-circumscribed, encapsulated, 5.5 cm in the greatest dimension
      and showed typical papillary and pseudopapillary structures. Capsular invasion
      was seen on focal areas. The patient was not given any adjuvant therapy and shows
      no sign of disease after six months follow-up. It is important to differentiate
      this tumor from other pancreatic neoplasms because this neoplasm is amenable to
      cure after complete surgical resection even in cases with capsular invasion,
      unlike malignant tumors of the pancreas. 

PMID- 24101359
TI  - No association between gout and Alzheimer's disease: results of a case-control
      study in older people in Taiwan.

PMID- 24101360
TI  - Brief geriatric depression scale as a measure of change in level of depression.

PMID- 24101361
TI  - Case series: extrapyramidal symptoms associated with use of aripiprazole in older
      adults.

PMID- 24101363
TI  - Long-term trends in incidence, survival and mortality of primary penile cancer in
      England.
AB  - PURPOSE: Few population-based studies exist of long-term trends in penile cancer.
      We report incidence and mortality trends in England over the 31 years 1979-2009
      and survival trends over the 40 years 1971-2010. METHODS: We calculated annual
      incidence and mortality rates per 100,000 by age and calendar period. We
      estimated incidence and mortality rate ratios for cohorts born since 1890, and
      one- and five-year relative survival (%) by age and deprivation category.
      RESULTS: A total of 9,690 men were diagnosed with penile cancer during 1979-2009.
      Age-standardized incidence rates increased by 21 %, from 1.10 to 1.33 per
      100,000. Mortality rates fell by 20 % after 1994, from 0.39 to 0.31 per 100,000.
      Survival analyses included 11,478 men diagnosed during 1971-2010. Five-year
      relative survival increased from 61.4 to 70.2 %. Five-year survival for men
      diagnosed 2006-2010 was 77 % for men aged under 60 years and 53 % for men aged 80
      99 years. The 8 % difference in five-year survival (66-74 %) between men in the
      most affluent and most deprived groups was not statistically significant.
      CONCLUSIONS: The 21 % increase in penile cancer incidence in England since the
      1970s may be explained by changes in sexual practice, greater exposure to
      sexually transmitted oncogenic human papilloma viruses, and decreasing rates of
      childhood circumcision. Improvement in survival is likely due to advances in
      diagnostic, staging and surgical techniques. There is a need for public health
      education and potential preventative strategies to address the increasing
      incidence.

PMID- 24101362
TI  - Effects of methionine synthase and methylenetetrahydrofolate reductase gene
      polymorphisms on markers of one-carbon metabolism.
AB  - Genetic and nutritional factors play a role in determining the functionality of
      the one-carbon (1C) metabolism cycle, a network of biochemical reactions critical
      to intracellular processes. Genes encoding enzymes for methylenetetrahydrofolate
      reductase (MTHFR) and methionine synthase (MTR) may determine biomarkers of the
      cycle including homocysteine (HCY), S-adenosylmethionine (SAM) and S
      adenosylhomocysteine (SAH). MTHFR C677T is an established genetic determinant of
      HCY but less is known of its effect on SAM and SAH. Conversely, the relationship
      between MTR A2756G and HCY remains inconclusive, and its effect on SAM and SAH
      has only been previously investigated in a female-specific population. Folate and
      vitamin B12 are essential substrate and cofactor of 1C metabolism; thus,
      consideration of gene-nutrient interactions may clarify the role of genetic
      determinants of HCY, SAM and SAH. This cross-sectional study included 570 healthy
      volunteers from Kingston, Ontario, Ottawa, Ontario and Halifax, Nova Scotia,
      Canada. Least squares regression was used to examine the effects of MTR and MTHFR
      polymorphisms on plasma HCY, SAM and SAH concentrations; gene-gene and gene
      nutrient interactions were considered with the inclusion of cross-products in the
      model. Main effects of MTR and MTHFR polymorphisms on HCY concentrations were
      observed; however, no gene-gene or gene-nutrient interactions were found. No
      association was observed for SAM. For SAH, interactions between MTR and MTHFR
      polymorphisms, and MTHFR polymorphism and serum folate were found. The findings
      of this research provide evidence that HCY and SAH, biomarkers of 1C metabolism,
      are influenced by genetic and nutritional factors and their interactions. 

PMID- 24101364
TI  - Other considerations about carcinogenicity of sulfur mustard.

PMID- 24101365
TI  - Heat-induced oxidative injury contributes to inhibition of Botrytis cinerea spore
      germination and growth.
AB  - The inhibitory effect of heat treatment (HT) on Botrytis cinerea, a major
      postharvest fungal pathogen, and the possible mode of action were investigated.
      Spore germination and germ tube elongation of B. cinerea were both increasingly
      and significantly inhibited by HT (43  degrees C) for 10, 20 or 30 min. HT
      induced gene expression of NADPH oxidase A, resulted in the intracellular
      accumulation of reactive oxygen species. HT-treated B. cinerea spores exhibited
      higher levels of oxidative damage to proteins and lipids, compared to the non-HT
      control. These findings indicate that HT resulted in oxidative damage which then
      played an important role in the inhibitory effect on B. cinerea. In the current
      study, HT was effective in controlling gray mold, caused by B. cinerea, in pear
      fruits. Understanding the mode of action by which HT inhibits fungal pathogens
      will help in the application of HT for management of postharvest fungal diseases
      of fruits and vegetables.

PMID- 24101366
TI  - Helicobacter pylori eradication in the prevention of gastric cancer: are more
      trials needed?
AB  - The incidence of gastric cancer has decreased in much of the world, but gastric
      cancer remains the second leading cause of cancer death globally, and the burden
      is growing in many countries in East Asia and Latin America. Chronic infection
      with Helicobacter pylori is the dominant cause of gastric cancer, and two recent
      randomized trials showed that H. pylori eradication significantly decreased
      gastric cancer risk. Population screening and treating individuals for H. pylori
      also appears to be cost-effective. Nevertheless, current clinical guidelines
      differ as to whether asymptomatic adults should be screened and treated for H.
      pylori, and no countries have yet implemented eradication programs. Some of this
      inaction may reflect lingering doubts about the effectiveness of H. pylori
      eradication in preventing gastric cancer, but there is also uncertainty about
      possible risks of mass antibiotic treatment and its impact on gut flora.
      Appropriately designed studies will help address these issues and hasten the
      implementation of population-wide prevention programs. 

PMID- 24101367
TI  - Approaches for drug delivery with intracortical probes.
AB  - Intracortical microprobes allow the precise monitoring of electrical and chemical
      signaling and are widely used in neuroscience. Microelectromechanical system
      (MEMS) technologies have greatly enhanced the integration of multifunctional
      probes by facilitating the combination of multiple recording electrodes and drug
      delivery channels in a single probe. Depending on the neuroscientific
      application, various assembly strategies are required in addition to the
      microprobe fabrication itself. This paper summarizes recent advances in the
      fabrication and assembly of micromachined silicon probes for drug delivery
      achieved within the EU-funded research project NeuroProbes. The described
      fabrication process combines a two-wafer silicon bonding process with deep
      reactive ion etching, wafer grinding, and thin film patterning and offers a
      maximum in design flexibility. By applying this process, three general comb-like
      microprobe designs featuring up to four 8-mm-long shafts, cross sections from
      150*200 to 250*250 um2, and different electrode and fluidic channel
      configurations are realized. Furthermore, we discuss the development and
      application of different probe assemblies for acute, semichronic, and chronic
      applications, including comb and array assemblies, floating microprobe arrays, as
      well as the complete drug delivery system NeuroMedicator for small animal
      research.

PMID- 24101368
TI  - Bioresorbable implants.

PMID- 24101369
TI  - Biological heart valves.
AB  - Cardiac valvular pathologies are often caused by rheumatic fever in young adults,
      atherosclerosis in elderly patients, or by congenital malformation of the heart
      in children, in effect affecting almost all population ages. Almost 300,000 heart
      valve operations are performed worldwide annually. Tissue valve prostheses have
      certain advantages over mechanical valves such as biocompatibility, more
      physiological hemodynamics, and no need for life-long systemic anticoagulation.
      However, the major disadvantage of biological valves is related to their
      durability. Nevertheless, during the last decade, the number of patients
      undergoing biological, rather than mechanical, valve replacement has increased
      from half to more than three-quarters for biological implants. Continuous
      improvement in valve fabrication includes development of new models and shapes,
      novel methods of tissue treatment, and preservation and implantation techniques.
      These efforts are focused not only on the improvement of morbidity and mortality
      of the patients but also on the improvement of their quality of life. Heart valve
      tissue engineering aims to provide durable, "autologous" valve prostheses. These
      valves demonstrate adaptive growth, which may avoid the need of repeated
      operations in growing patients.

PMID- 24101370
TI  - Optimizing the purification and analysis of miRNAs from urinary exosomes.
AB  - BACKGROUND: Exosomes are cytoplasm containing vesicles released by many cells
      that can be found in several biological fluids including urine. Urinary exosomes
      are released from every segment of the nephron, are detectable in urine,
      constitutively contain RNA (small RNAs and mRNAs) and harbor unique subset of
      proteins, reflecting their cellular source. METHODS: With the aim of establishing
      the optimal protocol for high throughput analysis of exosomal miRNAs, we compared
      three different urinary exosomes isolation methods and six RNA extraction
      techniques. Exosomal RNA yield, size and quality were assessed respectively by
      specific staining with fluorescent dye, capillary electrophoresis and analysis of
      spectrophotometric parameters. MiRNAs detection and abundance was determined by
      RT-qPCR. RESULTS: Among the exosomes isolation methods, Ultrafiltration resulted
      to be the most suited. The highest exosomal RNA yield quantified by RiboGreen(r)
      staining was obtained with the combination of TRI ReagentTM with miRNeasy(r),
      followed by TRI ReagentTM, SeraMirTM, miRCURYTM, mirVanaTM and miRNeasy(r); but
      after a multivariate analysis, SeraMirTM scored as the method of choice in terms
      of miRNA yield, purity and RT-qPCR miRNAs quantification accuracy. Storage
      conditions were also analyzed, showing that the relative abundance of urinary
      exosomal miRNAs is not influenced by urine freezing. CONCLUSIONS: The selection
      of appropriate urinary exosomal miRNA isolation method was dependent on various
      validation results. Ultrafiltration in combination with SeraMirTM exoRNA columns
      represents the optimal procedure for a rapid, cost-effective and efficient
      purification of miRNAs from urinary exosomes, perfectly suited for further
      applicative research in the field of miRNAs in kidney physiology and pathology.

PMID- 24101371
TI  - The ten commandments of laboratory testing for emergency physicians.

PMID- 24101372
TI  - Dose-dependent effect of aspirin on the level of sphingolipids in human blood.
AB  - PURPOSE: Aspirin is an antiplatelet drug which is commonly used in secondary
      prevention in ischemic heart disease and cerebrovascular events, and in newly
      diagnosed myocardial infarction. The aim of the present study was to examine
      effect of aspirin on the level of selected sphingolipid intermediates in plasma,
      erythrocytes and platelets. MATERIAL AND METHOD: Forty two healthy volunteers
      participated in the study. They were divided into two groups. In one group
      aspirin was given orally, daily, for one week in a dose of 75 mg (n=25). The
      subjects from the second group received one 300 mg dose of the drug (n=17). In
      both groups the blood was taken 4h after the last dose of aspirin. The following
      sphingolipid intermediates were quantified using high-pressure liquid
      chromatography: sphinganine, sphingosine, sphingosine-1-phosphate (S1P),
      sphinganine-1-phosphate (SA1P) and ceramide. RESULTS: It was found that lower
      dose of aspirin increased the level of S1P and ceramide in erythrocytes (by 23
      and 37%, respectively) having no effect on plasma and platelet sphingolipid
      levels. Higher dose of the drug reduced S1P and SA1P concentration in the plasma
      (by 16 and 10%, respectively). CONCLUSION: We conclude that aspirin interferes
      with sphingolipid metabolism in blood and that this effect depends on a dose of
      the drug. Since S1P is a potent cardioprotectant, the reduction in its plasma
      concentration after the loading dose of aspirin could be undesired side effect of
      the drug.

PMID- 24101373
TI  - Effects of tafamidis on transthyretin stabilization and clinical outcomes in
      patients with non-Val30Met transthyretin amyloidosis.
AB  - This phase II, open-label, single-treatment arm study evaluated the
      pharmacodynamics, efficacy, and safety of tafamidis in patients with non-Val30Met
      transthyretin (TTR) amyloidosis. Twenty-one patients with eight different non
      Val30Met mutations received 20 mg QD of tafamidis meglumine for 12 months. The
      primary outcome, TTR stabilization at Week 6, was achieved in 18 (94.7%) of 19
      patients with evaluable data. TTR was stabilized in 100% of patients with non
      missing data at Months 6 (n = 18) and 12 (n = 17). Exploratory efficacy measures
      demonstrated some worsening of neurological function. However, health-related
      quality of life, cardiac biomarker N-terminal pro-hormone brain natriuretic
      peptide, echocardiographic parameters, and modified body mass index did not
      demonstrate clinically relevant worsening during the 12 months of treatment.
      Tafamidis was well tolerated. In conclusion, our findings suggest that tafamidis
      20 mg QD effectively stabilized TTR associated with several non-Val30Met
      variants.

PMID- 24101374
TI  - 64Cu- and 68Ga-labelled [Nle(14),Lys(40)(Ahx-NODAGA)NH2]-exendin-4 for pancreatic
      beta cell imaging in rats.
AB  - PURPOSE: Glucagon-like peptide-1 receptor (GLP-1R) is a molecular target for
      imaging of pancreatic beta cells. We compared the ability of [Nle(14),Lys(40)(Ahx
      NODAGA-(64)Cu)NH2]-exendin-4 ([(64)Cu]NODAGA-exendin-4) and [Nle(14),Lys(40)(Ahx
      NODAGA-(68)Ga)NH2]-exendin-4 ([(68)Ga]NODAGA-exendin-4) to detect native
      pancreatic islets in rodents. PROCEDURES: The stability, lipophilicity and
      affinity of the radiotracers to the GLP-1R were determined in vitro. The
      biodistribution of the tracers was assessed using autoradiography, ex vivo
      biodistribution and PET imaging. Estimates for human radiation dosimetry were
      calculated. RESULTS: We found GLP-1R-specific labelling of pancreatic islets.
      However, the pancreas could not be visualised in PET images. The highest uptake
      of the tracers was observed in the kidneys. Effective dose estimates for
      [(64)Cu]NODAGA-exendin-4 and [(68)Ga]NODAGA-exendin-4 were 0.144 and 0.012
      mSv/MBq, respectively. CONCLUSION: [(64)Cu]NODAGA-exendin-4 might be more
      effective for labelling islets than [(68)Ga]NODAGA-exendin-4. This is probably
      due to the lower specific radioactivity of [(68)Ga]NODAGA-exendin-4 compared to
      [(64)Cu]NODAGA-exendin-4. The radiation dose in the kidneys may limit the use of
      [(64)Cu]NODAGA-exendin-4 as a clinical tracer.

PMID- 24101375
TI  - Transcription factor Runx2 controls the development and migration of plasmacytoid
      dendritic cells.
AB  - Plasmacytoid dendritic cells (pDCs) rapidly produce type I interferon (IFN-I) in
      response to viruses and are essential for antiviral immune responses. Although
      related to classical DCs (cDCs) in their development and expression profile, pDCs
      possess many distinct features. Unlike cDCs, pDCs develop in the bone marrow (BM)
      and emerge into peripheral lymphoid organs and tissues as fully differentiated
      cells. We now report that pDCs specifically express Runx2, a Runt family
      transcription factor that is essential for bone development. pDCs in Runx2
      deficient mice developed normally in the BM but were greatly reduced in the
      periphery. The defect was cell-intrinsic and was associated with the retention of
      mature Ly49Q(+) pDCs in the BM. Runx2 was required for the expression of several
      pDC-enriched genes, including the chemokine receptors Ccr2 and Ccr5. Mature pDCs
      expressed high levels of Ccr5 at the cell surface, and Ccr5-deficient pDCs in a
      competitive setting were reduced in the periphery relative to the BM. Thus, Runx2
      is required for the emergence of mature BM pDCs into the periphery, in a process
      that is partially dependent on Ccr5. These results establish Runx2 as a lineage
      specific regulator of immune system development. 

PMID- 24101376
TI  - BET bromodomain inhibition suppresses TH17-mediated pathology.
AB  - Interleukin (IL) 17-producing T helper (T(H)17) cells have been selected through
      evolution for their ability to control fungal and bacterial infections. It is
      also firmly established that their aberrant generation and activation results in
      autoimmune conditions. Using a characterized potent and selective small molecule
      inhibitor, we show that the bromodomain and extra-terminal domain (BET) family of
      chromatin adaptors plays fundamental and selective roles in human and murine
      T(H)17 differentiation from naive CD4(+) T cells, as well as in the activation of
      previously differentiated T(H)17 cells. We provide evidence that BET controls
      T(H)17 differentiation in a bromodomain-dependent manner through a mechanism that
      includes the direct regulation of multiple effector T(H)17-associated cytokines,
      including IL17, IL21, and GMCSF. We also demonstrate that BET family members Brd2
      and Brd4 associate with the Il17 locus in T(H)17 cells, and that this association
      requires bromodomains. We recapitulate the critical role of BET bromodomains in
      T(H)17 differentiation in vivo and show that therapeutic dosing of the BET
      inhibitor is efficacious in mouse models of autoimmunity. Our results identify
      the BET family of proteins as a fundamental link between chromatin signaling and
      T(H)17 biology, and support the notion of BET inhibition as a point of
      therapeutic intervention in autoimmune conditions.

PMID- 24101377
TI  - RhoA GTPase controls cytokinesis and programmed necrosis of hematopoietic
      progenitors.
AB  - Hematopoietic progenitor cells (HPCs) are central to hematopoiesis as they
      provide large numbers of lineage-defined blood cells necessary to sustain blood
      homeostasis. They are one of the most actively cycling somatic cells, and their
      precise control is critical for hematopoietic homeostasis. The small GTPase RhoA
      is an intracellular molecular switch that integrates cytokine, chemokine, and
      adhesion signals to coordinate multiple context-dependent cellular processes. By
      using a RhoA conditional knockout mouse model, we show that RhoA deficiency
      causes a multilineage hematopoietic failure that is associated with defective
      multipotent HPCs. Interestingly, RhoA(-/-) hematopoietic stem cells retained long
      term engraftment potential but failed to produce multipotent HPCs and lineage
      defined blood cells. This multilineage hematopoietic failure was rescued by
      reconstituting wild-type RhoA into the RhoA(-/-) Lin(-)Sca-1(+)c-Kit(+)
      compartment. Mechanistically, RhoA regulates actomyosin signaling, cytokinesis,
      and programmed necrosis of the HPCs, and loss of RhoA results in a cytokinesis
      failure of HPCs manifested by an accumulation of multinucleated cells caused by
      failed abscission of the cleavage furrow after telophase. Concomitantly, the HPCs
      show a drastically increased death associated with increased TNF-RIP-mediated
      necrosis. These results show that RhoA is a critical and specific regulator of
      multipotent HPCs during cytokinesis and thus essential for multilineage
      hematopoiesis. 

PMID- 24101378
TI  - Regulated vesicle fusion generates signaling nanoterritories that control T cell
      activation at the immunological synapse.
AB  - How the vesicular traffic of signaling molecules contributes to T cell receptor
      (TCR) signal transduction at the immunological synapse remains poorly understood.
      In this study, we show that the protein tyrosine kinase Lck, the TCRzeta subunit,
      and the adapter LAT traffic through distinct exocytic compartments, which are
      released at the immunological synapse in a differentially regulated manner. Lck
      vesicular release depends on MAL protein. Synaptic Lck, in turn, conditions the
      calcium- and synaptotagmin-7-dependent fusion of LAT and TCRzeta containing
      vesicles. Fusion of vesicles containing TCRzeta and LAT at the synaptic membrane
      determines not only the nanoscale organization of phosphorylated TCRzeta, ZAP70,
      LAT, and SLP76 clusters but also the presence of phosphorylated LAT and SLP76 in
      interacting signaling nanoterritories. This mechanism is required for priming IL
      2 and IFN-gamma production and may contribute to fine-tuning T cell activation
      breadth in response to different stimulatory conditions. 

PMID- 24101379
TI  - Cgnz1 allele confers kidney resistance to damage preventing progression of immune
      complex-mediated acute lupus glomerulonephritis.
AB  - Cgnz1 and Agnz1 on the distal region of mouse chromosome 1 are associated with
      chronic glomerulonephritis (cGN) and acute GN (aGN). NZM2328.Lc1R27 (R27) was
      generated by introgressing a C57L/J region where Cgnz1 is located to NZM2328. R27
      female mice developed aGN mediated by immune complex (IC) deposition and
      complement activation without progression to cGN with severe proteinuria. End
      stage renal disease (ESRD) was not seen in R27 mice as old as 15 mo. Thus, aGN
      and cGN are under separate genetic control, and IC-mediated proliferative GN need
      not progress to cGN and ESRD. NZM2328 and R27 female mice have comparable immune
      and inflammatory parameters. In contrast to NZM2328, R27 mice were resistant to
      sheep anti-mouse GBM serum-induced nephritis, supporting the hypothesis that aGN
      is mediated by autoimmunity and resistance to the development of cGN is mediated
      by end organ resistance to damage. Thus, autoimmunity should be considered
      distinct from end organ damage. The Cgnz1 region has been mapped to a 1.34 MB
      region with 45 genes. Nine candidate genes were identified. Clinical relevance of
      these observations is supported by case studies. Clinical implications and the
      significance to human lupus and other diseases are presented. 

PMID- 24101380
TI  - Cross talk between Wnt/beta-catenin and Irf8 in leukemia progression and drug
      resistance.
AB  - Progression and disease relapse of chronic myeloid leukemia (CML) depends on
      leukemia-initiating cells (LIC) that resist treatment. Using mouse genetics and a
      BCR-ABL model of CML, we observed cross talk between Wnt/beta-catenin signaling
      and the interferon-regulatory factor 8 (Irf8). In normal hematopoiesis,
      activation of beta-catenin results in up-regulation of Irf8, which in turn limits
      oncogenic beta-catenin functions. Self-renewal and myeloproliferation become
      dependent on beta-catenin in Irf8-deficient animals that develop a CML-like
      disease. Combined Irf8 deletion and constitutive beta-catenin activation result
      in progression of CML into fatal blast crisis, elevated leukemic potential of BCR
      ABL-induced LICs, and Imatinib resistance. Interestingly, activated beta-catenin
      enhances a preexisting Irf8-deficient gene signature, identifying beta-catenin as
      an amplifier of progression-specific gene regulation in the shift of CML to blast
      crisis. Collectively, our data uncover Irf8 as a roadblock for beta-catenin
      driven leukemia and imply both factors as targets in combinatorial therapy. 

PMID- 24101381
TI  - IL-4 directly signals tissue-resident macrophages to proliferate beyond
      homeostatic levels controlled by CSF-1.
AB  - Macrophages (MPhis) colonize tissues during inflammation in two distinct ways:
      recruitment of monocyte precursors and proliferation of resident cells. We
      recently revealed a major role for IL-4 in the proliferative expansion of
      resident MPhis during a Th2-biased tissue nematode infection. We now show that
      proliferation of MPhis during intestinal as well as tissue nematode infection is
      restricted to sites of IL-4 production and requires MPhi-intrinsic IL-4R
      signaling. However, both IL-4Ralpha-dependent and -independent mechanisms
      contributed to MPhi proliferation during nematode infections. IL-4R-independent
      proliferation was controlled by a rise in local CSF-1 levels, but IL-4Ralpha
      expression conferred a competitive advantage with higher and more sustained
      proliferation and increased accumulation of IL-4Ralpha(+) compared with IL
      4Ralpha(-) cells. Mechanistically, this occurred by conversion of IL-4Ralpha(+)
      MPhis from a CSF-1-dependent to -independent program of proliferation. Thus, IL-4
      increases the relative density of tissue MPhis by overcoming the constraints
      mediated by the availability of CSF-1. Finally, although both elevated CSF1R and
      IL-4Ralpha signaling triggered proliferation above homeostatic levels, only CSF-1
      led to the recruitment of monocytes and neutrophils. Thus, the IL-4 pathway of
      proliferation may have developed as an alternative to CSF-1 to increase resident
      MPhi numbers without coincident monocyte recruitment. 

PMID- 24101384
TI  - Current recommendations for bladder instillation therapy in the treatment of
      interstitial cystitis/bladder pain syndrome.
AB  - Bladder instillation therapy refers to the direct introduction of medication into
      the bladder and is a common treatment modality for patients with interstitial
      cystitis/bladder pain syndrome (IC/BPS) who have failed conservative and oral
      therapies. The current American Urological Association (AUA) recommendations list
      three medications as options for IC/BPS instillation therapy: dimethyl sulfoxide,
      heparin, and lidocaine. The purpose of this review is to examine the evidence
      behind the recommendations for these medications. We also examine several
      historical or experimental therapies that do not hold recommendations but are
      still used on rare occasion. Finally, we discuss our bladder instillation
      strategies as well as potential future research and development in intravesicular
      therapy. 

PMID- 24101382
TI  - Antigen-loaded MR1 tetramers define T cell receptor heterogeneity in mucosal
      associated invariant T cells.
AB  - Mucosal-associated invariant T cells (MAIT cells) express a semi-invariant T cell
      receptor (TCR) alpha-chain, TRAV1-2-TRAJ33, and are activated by vitamin B
      metabolites bound by the major histocompatibility complex (MHC)-related class I
      like molecule, MR1. Understanding MAIT cell biology has been restrained by the
      lack of reagents to specifically identify and characterize these cells.
      Furthermore, the use of surrogate markers may misrepresent the MAIT cell
      population. We show that modified human MR1 tetramers loaded with the potent MAIT
      cell ligand, reduced 6-hydroxymethyl-8-D-ribityllumazine (rRL-6-CH2OH),
      specifically detect all human MAIT cells. Tetramer(+) MAIT subsets were
      predominantly CD8(+) or CD4(-)CD8(-), although a small subset of CD4(+) MAIT
      cells was also detected. Notably, most human CD8(+) MAIT cells were
      CD8alpha(+)CD8beta(-/lo), implying predominant expression of CD8alphaalpha
      homodimers. Tetramer-sorted MAIT cells displayed a T(H)1 cytokine phenotype upon
      antigen-specific activation. Similarly, mouse MR1-rRL-6-CH2OH tetramers detected
      CD4(+), CD4(-)CD8(-) and CD8(+) MAIT cells in Valpha19 transgenic mice. Both
      human and mouse MAIT cells expressed a broad TCR-beta repertoire, and although
      the majority of human MAIT cells expressed TRAV1-2-TRAJ33, some expressed TRAJ12
      or TRAJ20 genes in conjunction with TRAV1-2. Accordingly, MR1 tetramers allow
      precise phenotypic characterization of human and mouse MAIT cells and revealed
      unanticipated TCR heterogeneity in this population.

PMID- 24101385
TI  - Expression of tricellulin in epithelial cells and non-epithelial cells.
AB  - Tricellulin is the first molecular component of tricellular tight junctions at
      tricellular contacts where three epithelial cells meet, and it is required for
      the their formation and maintenance of the epithelial barrier. Tricellulin binds
      other tight junction proteins, and its expression and distribution are affected
      by the bicellular tight junction protein occludin and lipolysis-stimulated
      lipoprotein receptor (LSR) which is expressed at tricellular contacts.
      Tricellulin is also detected in endothelial cells, neurons, microglia and
      astrocytes. Here, we focused tricellulin expression in various types of
      epithelial cells, nasal epithelial cells, pancreatic duct epithelial cells cells
      and hepatocytes, and non-epithelial cells, dendritic cells and Schwann cells,
      compared to expression of the bicellular tight junction protein occludin and LSR,
      and discuss the regulation and the role of tricellulin in cellular specificity.

PMID- 24101386
TI  - Myogenic cells applications in regeneration of post-infarction cardiac tissue.
AB  - Skeletal myoblasts (SMs) transplantations are the focus of intense investigation
      due to their therapeutic potential for cardiac repair. Heart diseases are the
      main problem in humans worldwide, resulting very often in death of patients.
      Consequently, investigators sought methods which could improve myocardial
      function in patients with cardiac failure. Stem cells therapy belongs to one of
      the highly promising and the most realistic methods of treating myocardial
      infarction. Despite the fact that many cell types were transplanted into damaged
      myocardium, autologous skeletal myoblasts seem to be the most encouraging cell
      source for myocardial repair due to their myogenic and contractile phenotype,
      biochemical and functional similarities to cardiac cells, high proliferative
      capacity in vitro and resistance to ischemia. Moreover, engrafted myoblasts could
      repopulate post-infarction scar and improve cardiac function. Unfortunately,
      transplanted SMs do not functionally or electrically integrate with the host
      myocardium, which could also cause ventricular arrhythmias, therefore, the use of
      these cells still remains a subject of intensive studies aiming at improvement of
      this therapeutic method. In this paper we recapitulate the current state of
      knowledge concerning the use of skeletal myoblasts in the treatment of post
      infarction scar tissue, and discuss the problems resulting from their
      applications. 

PMID- 24101387
TI  - The effect of reactive oxygen species on the synthesis of prostanoids from
      arachidonic acid.
AB  - Reactive oxygen species (ROS), such as hydrogen peroxide, superoxide anion
      radical or hydroxyl radical, play an important role in inflammation processes as
      well as in transduction of signals from receptors to interleukin -1beta (IL
      1beta), tumor necrosis factor alpha (TNF-alpha) or lipopolysaccharides (LPS).
      NADPH oxidase increases the ROS levels, leading to inactivation of protein
      phosphatase 1 (PP1), protein phosphatase 2A (PP2A) and protein tyrosine
      phosphatase (PTP): MAPK phosphatase 1 (MKP-1). Inactivation of phosphatases
      results in activation of mitogen-activated protein kinase (MAPK) cascades: c-Jun
      N-terminal kinase (JNK), p38 and extracellular signal-regulated kinase (Erk),
      which, in turn, activate cytosolic phospholipase A2 (cPLA2). ROS cause
      cytoplasmic calcium influx by activation of phospholipase C (PLC) and
      phosphorylation of IP3-sensitive calcium channels. ROS activate nuclear factor
      kappaB (NF-kappaB) via IkappaB kinase (IKK) through phosphoinositide 3-kinase
      (PI3K), tumor suppressor phosphatase and tensin homolog (PTEN) and protein kinase
      B (Akt/PKB) or NF-kappaB-inducing kinase (NIK). IKK phosphorylates NF-kappaB
      alpha subunit (IkappaBalpha) at Ser32. Oxidative stress inactivates NIK and
      IkappaB kinase gamma subunit/NF-kappaB essential modulator (IKKgamma/NEMO), which
      might cause activation of NF-kappaB that is independent on IKK and inhibitor of
      IkappaBalpha degradation, including phosphorylation of Tyr42 at IkappaBalpha by c
      Src and spleen tyrosine kinase (Syk), phosphorylation of the domain rich in
      proline, glutamic acid, serine and threonine (PEST) sequence by casein kinase II
      and inactivation of protein tyrosine phosphatase 1B (PTP1B). NF-kappaB and MAPK
      cascades-activated transcription factor activator protein 1 (AP-1) and CREB
      binding protein (CBP/p300) lead to expression of cytosolic phospholipase A2
      (cPLA2), cyclooxygenase-2 (COX-2) and membrane-bound prostaglandin E synthase 1
      (mPGES-1), and thus to increased release of arachidonic acid and production of
      prostaglandins, particularly prostaglandin E2 (PGE2). ROS increase the activity
      of hematopoietic-type PGD synthase (H-PGDS), and, as a result, the production of
      prostaglandin D2 (PGD2). However, the superoxide radical reacts with nitric oxide
      forming peroxynitrite that inactivates prostaglandin I synthase (PGIS),
      suppressing the production of prostaglandin I2 (PGI2). ROS do not affect
      thromboxane synthesis in a direct manner; this is achieved by an increase in
      cPLA2 activity and COX-2 expression. The aim of this review was to summarize
      knowledge of influence of ROS on the synthesis of prostanoids from arachidonic
      acid.

PMID- 24101388
TI  - Influence of fundectomy and intraperitoneal or intragastric administration of
      apelin on apoptosis, mitosis, and DNA repair enzyme OGG1,2 expression in adult
      rats gastrointestinal tract and pancreas.
AB  - Apelin, endogenous ligand of G protein-coupled apelin receptor (APJ), is released
      into the gastrointestinal lumen, however, local effect of luminal apelin on gut
      epithelium has not been elucidated so far. The present study aimed to determine
      the effects of fundectomy, and intraperitoneal or intragastric administration of
      apelin on pancreatic, gastric and intestinal epithelium apoptosis, mitosis and
      DNA repair enzyme OGG1,2 expression in adult Wistar rats. Apelin-13 was given by
      intraperitoneal or gastric gavage twice a day for 10 days (100 nmol/kg b.
      wt./day). Fundectomized rats did not receive apelin. Control groups received
      saline as placebo. At the end of the experiment the rats were sacrificed and the
      pancreas, gastric fundus, duodenum, middle jejunum and colon tissue samples were
      harvested for immunofluorescence studies. Intraperitoneal and intragastric apelin
      13 reduced apoptosis, mitosis and number of DNA damages in rats gastrointestinal
      tract (p<=0.001) as compared to control. In fundectomized rats, the apoptotic
      index in the pancreas and colon was decreased (p<0.001), and in the stomach and
      jejunum was increased (p<0.001). Mitotic index was decreased in all
      gastrointestinal tissues. Number of DNA damages (p<=0.001) in fundectomized rats
      was reduced except stomach where OGG1,2 expression was increased (p<=0.001) as
      compared to control. In conclusion, circulating and luminal exogenous apelin-13
      caused similar effects on intestinal epithelium. Endogenous (gastric) apelin is
      important for renewal of intestinal epithelium in adult rats. Pharmacological
      doses of apelin-13 may reduce the cell turnover in the upper gastrointestinal
      tract epithelium and pancreas, and improve the overall gut health. 

PMID- 24101389
TI  - Gastrin promotes intestinal polyposis through cholecystokinin-B receptor-mediated
      proliferative signaling and fostering tumor microenvironment.
AB  - Increased serum gastrin concentrations in patients with colorectal cancer
      suggested the tumorigenic trophic effect of gastrin. Detailed and global
      molecular mechanisms explaining trophic effect of gastrin had not been revealed.
      In the current study, intestinal polyposis of APC(Min/+) mice was compared
      between phosphate buffered saline (PBS) injected and gastrin (10 MUg/kg, thrice
      per week) injected group. Total number of intestinal polyposis was counted and
      immunohistochemical staining with F4/80 and CD3 was done. MTT assay, cell cycle
      analysis, and Western blot for cyclin D1, CDK4, and beta-catenin were performed
      in Raw 264.7 and HCT116 cells before and after gastrin administration.
      Experiments were repeated with YM022 or transfection with si-cholecystokinin-B
      receptor (CCK-B-R). Intraperitoneal gastrin significantly increased intestinal
      polyposis in APC(Min/+) mice (P<0.005), in which significant increases in
      macrophage were noted on F4/80 immunohistochemical staining (Plt;0.05) as well as
      Ki-67 staining (Plt;0.05) after gastrin. On comparative cytokine array, gastrin
      increased interleukin-1beta (IL-1beta), interleukin 3Rbeta (IL-3Rbeta), stromal
      cell-derived factor-1alpha (SDF-1alpha), thymus and activation-regulated
      chemokine (TARC), and thymus-derived chemotactic agent 3 (TCA-3) in macrophage
      cells, which was further confirmed with real time polymerase chain reaction (RT
      PCR) analysis (P<0.05). In addition to increased inflammatory cytokines, gastrin
      increased macrophage proliferation accompanied with increased cyclin D1 and CDK4.
      Targeted for HCT116 cells, gastrin significantly increased proliferation as well
      as increases in synthetic phase of cell cycle. YM022 as gastrin antagonist
      significantly abolished the trophic actions of gastrin (P<0.05). HCT116 cells
      transfected with siCCK-B-R, gastrin did not increase either cell cycle or beta
      catenin in spite of gastrin administration. Conclusively, gastrin promoted
      intestinal polyposis through either direct gastrin receptor-mediated
      proliferative signaling or fostering tumor microenvironment such as macrophage
      activation.

PMID- 24101390
TI  - A study comparing the efficacy of antimicrobial agents versus enzyme (P-gp)
      inducers in the treatment of 2,4,6 trinitrobenzenesulfonic acid-induced colitis
      in rats.
AB  - The intestinal microflora is an important cofactor in the pathogenesis of
      intestinal inflammation; and the epithelial cell barrier function is critical in
      providing protection against the stimulation of mucosal immune system by the
      microflora. In the present study, therapeutic role of the antibacterial drugs
      rifampicin and ciprofloxacine were investigated in comparison to spironolactone,
      an enzyme inducer, in 2,4,6-trinitrobenzenesulfonic acid (TNBS)-induced colitis
      of the rats. Drugs were administered for 14 days following induction of colitis.
      All drug treatments ameliorated the clinical hallmarks of colitis as determined
      by body weight loss and assessment of diarrhea, colon length, and histology.
      Oxidative damage and neutrophil infiltration as well as nuclear factor kappaB (NF
      kappaB) and tumor necrosis factor alpha (TNF-alpha) expressions that were
      increased during colitis, were decreased significantly. Rifampicin and
      ciprofloxacin were probably effective due to their antibacterial and
      immunomodulating properties. The multidrug resistence gene (MDR1) and its product
      p-glycoprotein (P-gp) has been implicated in the pathogenesis of inflammatory
      bowel disease (IBD). In the present study, findings of the P-gp expression were
      inconclusive but regarding previous studies, it can be suggested that the
      beneficial effects of rifampicin and spironolactone may be partly due to their
      action as a P-gp ligand. Spironolactone has been reported to supress the
      transcription of proinflamatory cytokines that are considered to be of importance
      in immunoinflammatory diseases. It is also a powerful pregnane X receptor (PXR)
      inducer; thus, inhibition of the expression of NF-kappaB and TNF-alpha, and
      amelioration of inflammation by spironolactone suggest that this may have been
      through the activation of PXR. However, our findings regarding PXR expression
      were inconclusive. Activation of PXR by spironolactone probably also contributed
      to the induction of P-gp, resulting in extrusion of noxious substances from the
      tissue. 

PMID- 24101391
TI  - Cinacalcet, a calcimimetic, prevents nonsteroidal antiinflammatory drug-induced
      small intestinal damage in rats.
AB  - The extracellular calcium-sensing receptor (CaSR), a G protein-coupled cell
      receptor cloned from bovine parathyroid, has been demonstrated to play a
      regulatory role in various functions of the gastrointestinal tract. In the
      present study, we examined the effect of cinacalcet, a drug that acts as a
      calcimimetic through the allosteric activation of CaSR, on the loxoprofen-induced
      small intestinal lesions and investigated the mechanisms involved in the
      protective action. Male Sprague-Dawley rats were used without fasting. The
      animals were administered loxoprofen p.o. and euthanized 24 hours later and the
      intestinal mucosa was examined for lesions. Cinacalcet was given p.o. twice, 30
      min before and 6 h after loxoprofen. Loxoprofen caused hemorrhagic lesions in the
      small intestine, accompanied by the upregulation of enterobacterial invasion,
      myeloperoxidase (MPO) activity and inducible nitric oxide synthase (iNOS)/tumor
      necrosis factor alpha (TNF-alpha) expression as well as the downregulation of
      Muc2 expression. Prior administration of cinacalcet dose-dependently and
      significantly reduced the severity of these lesions in response to loxoprofen,
      with concomitant suppression of the changes in bacterial invasion, iNOS/TNF-alpha
      as well as Muc2 expression, and myeloperoxidase activity. Cinacalcet also
      significantly reversed a decrease in mucus secretion and fluid secretion in the
      small intestine caused by loxoprofen, but had no effect on the intestinal
      hypermotility or prostaglandin E2 deficiency caused by loxoprofen. These results
      suggest that cinacalcet protects the small intestine against loxoprofen-induced
      damage, and this effect may be functionally associated with an increase in fluid
      secretion and a reversal of downregulation of Muc2 expression caused by
      loxoprofen, resulting in suppression of bacterial invasion and iNOS/TNF-alpha
      expression, the major pathogenic events in nonsteroidal antiinflammatory drugs
      induced small intestinal ulceration.

PMID- 24101392
TI  - Human endothelial lecitin-like oxLDL receptor-1 (LOX-1) expression is not
      associated with impairment of endothelium-dependent vasoreactivity in conduit
      vessels.
AB  - The cellular uptake of oxidized low density lipoprotein (LDL) is mediated through
      the oxidized LDL receptor-1, LOX-1. We investigated whether circulating factors
      link LOX-1 expression in endothelial cells and impaired endothelium-dependent
      vasoreactivity (EDVR) as functional indicator of atherogenesis. EDVR was measured
      as flow-mediated dilation (FMD) of the brachial artery in 27 patients with a
      known history of cardiovascular disease. Human umbilical vein endothelial cells
      (HUVEC) were incubated with bradykinin or prostacyclin in the presence of tumour
      necrosis factor-alpha (TNF-alpha) or with serum of each patient for four hours.
      Total mRNA and protein extracts were analysed for LOX-1 and eNOS expression
      relative to the expression in medium-treated cells and corrected for GAPDH
      expression. RESULTS: Prostacyclin and bradykinin did not modulate LOX-1 basal
      expression but were able to prevent significantly the up-regulation of LOX-1
      expression by TNF-alpha, in HUVEC in vitro. Impaired EDVR was associated
      significantly with reduced endothelial nitric oxide synthase (eNOS) protein
      expression in HUVEC (r=0.788, P<0.001), diabetes (P=0.024), and smoking status
      (yes/no, P=0.047). In contrast, no such association was established with LOX-1
      mRNA (r=0.292, P=0.138) or with LOX-1 protein expression in HUVEC (r=0.201,
      P=0.312). CONCLUSIONS: Using a combination of in vitro experiments with in vivo
      measurements, we found no evidence that endothelial LOX-1 expression and EDVR
      mediated through circulating factors were associated.

PMID- 24101393
TI  - Decreased secretion of vascular endothelial growth factor is associated with
      increased apoptosis in vascular tumor derived endothelial cells.
AB  - Bleomycin is an antineoplastic drug that has recently been employed to treat
      haemangiomas, the most common vascular tumors of infancy, with very good results.
      To better understand the mechanism of bleomycin in accelerating haemangioma
      regression, we have investigated the effects of the drug on vascular tumor
      inducing endothelial cells (sEnd.2 cells). Cell growth studies were undertaken
      using crystal violet staining, while morphological studies were undertaken
      employing transmission electron microscopy. The cells were analyzed for possible
      apoptosis employing flow cytometry. The expression of Bcl-2 and p53 were
      investigated using Western blot analysis. In addition, the production of vascular
      endothelial growth factor was measured using ELISA. Results showed that bleomycin
      inhibited the growth of these endothelial cells, even in the presence of vascular
      endothelial growth factor, a proangiogenic growth factor. Further, there was
      increased endothelial cell apoptosis, as evidenced by morphological analysis,
      increased acridine orange staining of cell nuclei and annexin V staining.
      Apoptosis was associated with an increase in the expression of p53 and a decrease
      in the expression of the antiapoptotic protein Bcl-2. 

PMID- 24101398
TI  - The effects of mu-, delta- and kappa-opioid receptor activation on luteinizing
      and follicle-stimulating hormone secretion from porcine pituitary cells.
AB  - Endogenous opioid peptides (EOP) are involved, among others, in the regulation of
      endocrine systems, including gonadotropin (LH and FSH) secretion in females
      during the estrous cycle. EOP preferentially act through three major types of
      opioid receptors: mu (MOP), delta (DOP) and kappa (KOP). Their influence on
      gonadotropin secretion at the hypothalamic level was extensively studied in
      different species, but information pertaining to their modulatory action on LH
      and FSH secretion at the pituitary level is scarce. Therefore, the aim of the
      present study was to examine the effects of opioid receptor agonists (mu--DAMGO,
      delta--DPDPE and kappa--U 50.488) at doses 10-9, 10-8, 10-7 mol/L on both basal
      and GnRH-stimulated gonadotropin (LH and FSH) secretion in vitro from the
      anterior pituitary cells of gilts on days 8-10 (luteal phase) and 19-20
      (follicular phase) of the estrous cycle. The exposition of pituitary cells in
      vitro to kappa-receptor agonist (U 50.488; 10-7 mol/L) significantly reduced
      (p<0.05) basal secretion of LH during both phases of the estrous cycle. The GnRH
      stimulated LH secretion was also decreased (p<0.05) by this agonist during the
      luteal phase (10-7 mol/L) and follicular phase (10-9, 10-8 and 10-7 mol/L). In
      turn, the FSH secretion was reduced (p<0.05) by kappa-agonist only in the
      presence of GnRH during the luteal phase (10-8 and 10-7 mol/L) and follicular
      phase (10-7 mol/L). The delta-opioid agonist (DPDPE) significantly reduced
      (p<0.05) the GnRH-affected secretion of LH during the follicular phase (10-8
      mol/L) and FSH during the luteal phase (10-7 mol/L). The mu-opioid agonist
      (DAMGO) affected neither LH nor FSH secretion. These results indicate that opioid
      peptides, acting mainly through kappa- and delta-opioid receptors, may
      participate in the modulation of gonadotropin (LH and FSH) secretion at the
      pituitary level in cyclic gilts.

PMID- 24101396
TI  - Involvement of the monoaminergic system in the antidepressant-like activity of
      chromium chloride in the forced swim test.
AB  - Bio-metal chromium(III) is a crucial microelement for the proper functioning of
      living organisms. Previous preclinical and clinical studies reported its
      potential antidepressant properties. The aim of the present study was to examine
      the effect of antidepressants and noradrenergic and dopaminergic receptor
      antagonists on chromium chloride (CrCl3) activity in the forced swim test (FST)
      in mice and rats. Imipramine (5 mg/kg), fluoxetine (5 mg/kg) and reboxetine (5
      mg/kg) but not bupropion (1 mg/kg), administered jointly with CrCl3 at a dose of
      6 mg/kg, reduced the immobility time in the FST in mice. The reduction of the
      immobility time induced by the active dose (12 mg/kg) of CrCl3 was completely
      abolished by propranolol (2 mg/kg, beta-adrenoceptor antagonist), SCH 23390 (0.5
      mg/kg, a dopamine D1 receptor antagonist), and partially by prazosin (1 mg/kg, an
      alpha1-adrenoceptor antagonist), yohimbine (1 mg/kg, an alpha2-adrenoceptor
      antagonist) and sulpiryd (50 mg/kg, a dopamine D2/D3 receptor antagonist)
      administration. The locomotor activity was significantly reduced by CrCl3 +
      reboxetine treatment, which did not influence the reboxetine enhancement of the
      antidepressant-like effect of CrCl3 in the FST. Moreover, CrCl3 at a dose of 32
      mg/kg (although not at 12 mg/kg) significantly reduced the immobility and
      enhanced the climbing (but not swimming) time in the FST in rats, which indicates
      the involvement of the noradrenergic pathway in this effect. The present study
      indicates that the antidepressant-like activity of chromium in the FST is
      dependent (although to a different extent) on the noradrenergic, dopaminergic and
      serotonin systems.

PMID- 24101399
TI  - In vitro effects of luteinizing hormone, progesterone and oestradiol-17beta on
      leptin gene expression and leptin secretion by porcine luteal cells obtained in
      early pregnancy.
AB  - Leptin, the product of the ob gene, is involved in the control of ovarian
      functions. Leptin transcripts and OB proteins were localized in the porcine
      corpus luteum, but the regulatory mechanism of leptin mRNA expression and leptin
      secretion in porcine luteal cells remains unexplained. The aim of the present
      study was to: 1) determine level of leptin and long form of leptin receptor (OB
      Rb) transcript/protein in dispersed porcine luteal cells on days 14-16 of
      pregnancy and 2) examine, in vitro, the effects of luteinizing hormone (LH),
      17beta-oestradiol (E2) and progesterone (P4) on leptin gene expression and leptin
      secretion by those cells. Isolated luteal cells were first precultured (48 hours)
      and then cultured in the presence or absence of luteinizing hormone (LH) (1; 10;
      100 ng/ml), E2 (0.02; 0.2; 2; 20 ng/ml) and P4 (20; 100; 200 ng/ml) for 24 hours.
      Leptin and OB-Rb transcript/protein were detected in porcine luteal cells by real
      time PCR and fluorescence immunocytochemistry (F-ICC), respectively. A higher
      level of leptin mRNA expressions in the cells was observed in the presence LH (10
      ng/ml), E2 (0.02 ng/ml) and P4 (200 ng/ml). The results of an RIA assay revealed
      increased leptin secretion when the luteal cells were treated with E2 (20 ng/ml)
      and P4 (200 ng/ml). LH did not affect leptin release by those cells. We conclude:
      1) that leptin and OB-Rb genes/proteins are expressed in porcine luteal cells and
      2) there is a modulatory effect of: LH, E2 and P4 on leptin mRNA expression as
      well as E2 and P4 on leptin secretion by those cells obtained in early pregnancy.

PMID- 24101397
TI  - Diazepam and its metabolites in the mothers' and newborns' hair as a biomarker of
      prenatal exposure.
AB  - Pregnant women are exposed to benzodiazepines for therapeutic purposes during
      gestation. The goal of this study was to evaluate prenatal exposure to
      benzodiazepines. Time of exposure during course of pregnancy is a significant
      aspect of fetal exposure to drugs. Benzodiazepine concentration assay in hair of
      mothers and newborns exposed prenatally to these drugs was performed in the
      studies. Development, validation and evaluation of benzodiazepine determination
      method in mothers and their newborns enables assessment of health risks for the
      child and implementation of adequate therapeutic procedures. We used A LC-ESI
      MS/MS method that allowed determination of diazepam (the main benzodiazepine used
      by pregnant women was diazepam) and its metabolites (nordazepam, oxazepam) in
      hair of mothers and newborns. LOQ 10 pg/mg of hair was used in the study.
      RESULTS: concentration of nordazepam was higher than parent drug (diazepam) and
      higher in newborns' hair when compared to mothers'. The mean concentrations of
      diazepam in mothers' hair were 31.6+/-36.0 and 34.1+/-42.4 pg/mg in the second
      and third trimester of pregnancy respectively. The mean concentration of diazepam
      in newborns' hair was higher and reached levels of 53.3+/-36.5 pg/mg. The mean
      concentration of nordazepam in the mothers' hair corresponding to the second and
      third trimester was 52.9+/-48.1 and 89.9+/-122.8 pg/mg, respectively. Nordazepam
      in the newborns' hair was detected at the mean level of 108.1+/-144.2 pg/mg. It
      was concluded that diazepam and nordazepam are permanently incorporated into the
      hair structure. Presence of diazepam and its metabolites in newborn's hair
      confirms that these benzodiazepines permeate placental barrier. Segmental
      analysis of mothers' hair enabled the assessment of drug administration time.
      Diazepam and its metabolites determined in hair of newborns may serve as
      biomarkers of prenatal exposure to these drugs. The performed LC-MS/MS analysis
      was accurate enough to determine even low concentrations of benzodiazepines, at
      the level of few pg/mg of hair. Levels of diazepam detected in hair of newborns
      were higher than levels determined in mothers. This may confirm the fact, that
      fetus's ability to metabolize diazepam is scarce. Nordazepam was found in higher
      concentrations in hair of newborns than in hair of mothers, which may suggest
      that it is cumulated in child's organism. Other metabolites of diazepam--oxazepam
      and temazepam--were detected in very few cases, in low concentrations.

PMID- 24101394
TI  - Bronchodilator, vasodilator and spasmolytic activities of methanolic extract of
      Myrtus communis L.
AB  - The present study was undertaken to validate some of the folkloric claims about
      the effectiveness of the use of a Myrtus communis L. crude methanol extract
      (Mc.Cr) in gastrointestinal, respiratory and vascular diseases. Mc.Cr caused
      complete relaxation of spontaneous and K+ (80 mM)-induced contractions in
      isolated rabbit jejunum. It caused right ward parallel shift of calcium
      concentration response curves. Mc.Cr exhibited relaxant effect on CCh- and K+ (80
      mM)-induced contractions in isolated rabbit tracheal preparations. Furthermore,
      Mc.Cr caused relaxation of phenylephrine (1 MUM)- and K+ (80 mM)-induced
      contractions in isolated rabbit aorta preparations. These effects were similar to
      verapamil, a standard calcium channel blocker. These findings could be the basis
      for explaining the spasmolytic, bronchodilator and vasodilator activities of the
      extract, through a possible calcium channel blocking activity.

PMID- 24101395
TI  - Remifentanil reversibly abolished phrenic long term facilitation in rats
      subjected to acute intermittent hypoxia.
AB  - The aim was to investigate whether intravenous infusion of remifentanil would
      depress phrenic long term facilitation (pLTF) evoked by acute intermittent
      hypoxia (AIH) in adult, male, urethane anaesthetized Sprague-Dawley rats,
      bilaterally vagotomized, paralyzed and mechanically ventilated. The experimental
      group received a remifentanil infusion (0.5 MUg/kg/min i.v., n=12), whereas the
      control group (n=6) received saline. Rats were exposed to AIH protocol. Phrenic
      nerve amplitude (PNA), burst frequency (f) and breathing rhythm parameters (Ti,
      Te, Ttot) were analyzed during 5 hypoxias and at 15, 30, and 60 minutes after the
      final hypoxia, and compared to baseline values. At the end of the experiment, the
      infusion of remifentanil was stopped and phrenic nerve activity was compared to
      baseline values prior to remifentanil infusion. In the control group, peak
      phrenic nerve activity (pPNA) significantly increased at 60 min (T60, increase by
      138.8+/-28.3%, p=0.006) after the last hypoxic episode compared to baseline
      values, i.e. pLTF was induced. In remifentanil treated rats, there were no
      significant changes in peak phrenic nerve activity at T60 compared to baseline
      values (decrease by 5.3+/-16.5%, p>0.05), i.e. pLTF was abolished. Fifteen
      minutes following cessation of remifentanil infusion, pPNA increased by 93.2+/
      40.2% (p<0.05) and remained increased compared to pre-remifentanil-infusion
      values for more than 30 minutes, i.e. pLTF could be observed after cessation of
      the remifentanil infusion. In conclusion, the short acting MU-opioid receptor
      agonist, remifentanil, reversibly abolished phrenic long term facilitation in
      urethane anesthetized rats.

PMID- 24101400
TI  - Altered monocyte calcium-sensing receptor expression in patients with type 2
      diabetes mellitus and atherosclerosis.
AB  - The increased cardiovascular risk in type 2 diabetes mellitus (DM2) is the result
      of disorders of the immune system, including the enhanced reactivity of monocytes
      and impaired secretion of inflammatory cytokines. The aim of this study was to
      analyze the expression of calcium-sensing receptor (CaR) in peripheral blood
      monocytes of individuals with DM2 and peripheral artery disease (PAD). The study
      included 88 individuals, among them 37 patients with PAD (group A-
      atherosclerosis), 27 individuals with DM2 and PAD (group AD--atherosclerosis and
      diabetes mellitus), and 24 controls (group C--controls). The expression of CaR on
      isolated peripheral blood monocytes was analyzed at the level of surface protein
      (CaR(surf)) and mRNA (CaR(mRNA)). Concentrations of pro-inflammatory cytokines
      were determined by means of ELISA, while the severity of PAD was assessed with
      Doppler and impedance plethysmography. The expression of CaR(surf) was the
      highest in the controls (mean 41.27%) and did not differ significantly as
      compared to individuals from group AD (35.66%); however it was significantly
      higher than in group A (24.49%). The expression of CaR(surf) was related to the
      severity of PAD, fasting concentration of glucose, and the concentration of
      monocyte chemotactic protein (MCP-1). Additionally, significant differences were
      observed with regards to CaR(mRNA) expression; although, no significant
      relationships were documented between CaR(mRNA) and laboratory or clinical
      variables. Different ways of CaR(surf) and CaR(mRNA) expression regulation were
      associated with the concentration of osteopontin. CONCLUSION: A nearly 1.5-fold
      higher expression of CaR(surf) on the peripheral blood monocytes of individuals
      with diabetes and PAD manifests during post-transcription stage and depends on
      fasting glucose concentration and MCP-1 concentration on one hand, and the
      severity of PAD on the other.

PMID- 24101403
TI  - Developmentally adapted cognitive processing therapy for adolescents suffering
      from posttraumatic stress disorder after childhood sexual or physical abuse: a
      pilot study.
AB  - Although childhood sexual abuse and childhood physical abuse (CSA and CPA) have
      severe psychopathological consequences, there is little evidence supporting
      psychotherapeutic interventions for adolescents who have experienced CSA or CPA.
      To provide a treatment tailored to the specific needs of adolescents suffering
      from abuse-related posttraumatic stress disorder (PTSD), we modified Cognitive
      Processing Therapy (CPT) by adding new treatment modules and changing the therapy
      setting. To evaluate the feasibility and efficacy of Developmentally Adapted CPT
      (D-CPT), we treated 12 adolescents suffering from PTSD secondary to CSA or CPA.
      Patients were assessed prior to treatment (t0), post-treatment (t1), and 6 weeks
      after treatment (t2). Assessments included the Clinician-Administered PTSD Scale
      (CAPS), the UCLA PTSD Index (UCLA), the Children's Depression Inventory (CDI),
      the Adolescent Dissociative Experiences Scale (A-DES), and the Borderline Symptom
      List (BSL-23). MANOVAs revealed that posttraumatic stress measurements and
      associated symptom measurements significantly differed across time points. When
      comparing t0 with t2, Cohen's d was large with respect to the CAPS scores (d =
      1.45, p < .001) and the UCLA scores (d = 1.91, p < .001). Cohen's d had a medium
      magnitude with respect to the CDI scores (d = .78, p < .001), the A-DES scores (d
      = 0.64, p < .05), and the BSL-23 scores (d = 0.74, p < .01). D-CPT has the
      potential to reduce PTSD symptoms and comorbid psychopathology in adolescents
      with histories of CSA or CPA.

PMID- 24101404
TI  - Case formulation with offenders: what, who, where, when, why and how?

PMID- 24101402
TI  - Introducing a special edition of the Journal of Muscle Research and Cell Motility
      on tropomyosin: form and function.

PMID- 24101401
TI  - A concise panel of biomarkers identifies neurocognitive functioning changes in
      HIV-infected individuals.
AB  - Neurocognitive (NC) impairment (NCI) occurs commonly in people living with HIV.
      Despite substantial effort, no biomarkers have been sufficiently validated for
      diagnosis and prognosis of NCI in the clinic. The goal of this project was to
      identify diagnostic or prognostic biomarkers for NCI in a comprehensively
      characterized HIV cohort. Multidisciplinary case review selected 98 HIV-infected
      individuals and categorized them into four NC groups using normative data: stably
      normal (SN), stably impaired (SI), worsening (Wo), or improving (Im). All
      subjects underwent comprehensive NC testing, phlebotomy, and lumbar puncture at
      two timepoints separated by a median of 6.2 months. Eight biomarkers were
      measured in CSF and blood by immunoassay. Results were analyzed using mixed model
      linear regression and staged recursive partitioning. At the first visit, subjects
      were mostly middle-aged (median 45) white (58 %) men (84 %) who had AIDS (70 %).
      Of the 73 % who took antiretroviral therapy (ART), 54 % had HIV RNA levels below
      50 c/mL in plasma. Mixed model linear regression identified that only MCP-1 in
      CSF was associated with neurocognitive change group. Recursive partitioning
      models aimed at diagnosis (i.e., correctly classifying neurocognitive status at
      the first visit) were complex and required most biomarkers to achieve
      misclassification limits. In contrast, prognostic models were more efficient. A
      combination of three biomarkers (sCD14, MCP-1, SDF-1alpha) correctly classified
      82 % of Wo and SN subjects, including 88 % of SN subjects. A combination of two
      biomarkers (MCP-1, TNF-alpha) correctly classified 81 % of Im and SI subjects,
      including 100 % of SI subjects. This analysis of well-characterized individuals
      identified concise panels of biomarkers associated with NC change. Across all
      analyses, the two most frequently identified biomarkers were sCD14 and MCP-1,
      indicators of monocyte/macrophage activation. While the panels differed depending
      on the outcome and on the degree of misclassification, nearly all stable patients
      were correctly classified. 

PMID- 24101405
TI  - Complex forensic case formulation in recovery-oriented services: some
      implications for routine practice.

PMID- 24101406
TI  - Structured professional judgement and sequential redirections.
AB  - BACKGROUND: Findings from violence risk assessment prediction-outcome studies
      suggest that there is no overall 'standout' scheme. AIM: This paper aims to
      highlight that even greater attention is now required on intervention-focused
      research. METHODS: Recent advances in the development of structured professional
      judgement schemes, such as the Historical, Clinical, Risk Management-20 (Version
      3), are considered when applied to the tasks of refining individual case
      formulation and risk management planning. The paper also considers social science
      research relevant to improving interventions aimed at preventing violence and
      related risks. RESULTS: A sequential redirection treatment model is proposed on
      the basis of our limited understanding of how interventions 'work' when applied
      to mentally disordered offenders. CONCLUSIONS AND IMPLICATIONS FOR PRACTICE:
      Future developments in violence-reduction interventions will require improved
      integration between the worlds of research and clinical practice.

PMID- 24101407
TI  - An evaluation of case formulation training and consultation with probation
      officers.
AB  - BACKGROUND: Formulation is a core competency of mental health professionals,
      drawing on a variety of sources of information. In England and Wales, the current
      strategy for offenders with personality disorder places formulation-led
      management, generally by probation staff, at its core, but reliability and
      validity of the process remain unclear. AIMS: The first aim was to evaluate a
      checklist previously designed to establish quality of formulation, and the second
      to measure the impact of training and consultation on the ability of probation
      officers to formulate cases. METHODS: The inter-rater reliability, test-re-test
      reliability and internal consistency of the McMurran formulation checklist were
      calculated from the scores derived from randomised formulations completed by
      probation officers from fictitious case vignettes. The impact of training was
      measured by comparing pre- and post-training formulations of these vignettes.
      Practice cases formulated by probation officers at psychologist-facilitated
      consultation meetings over a 6-month period were used to measure the impact of
      consultation. All formulations were scored blind by independent experts. RESULTS:
      Inter-rater reliability, test-re-test reliability and internal consistency of the
      scale were all acceptable. Training and practice did not significantly improve
      the probation officers' formulations. CONCLUSIONS: The purpose and utility of
      formulation may vary according to the context in which it is applied. Progress in
      developing formulation skills may depend on the nature and length of the previous
      experience of this skill. Future research should take account of such variance,
      with this scale as a potentially useful aid in monitoring progress. IMPLICATIONS:
      The capacity for teaching formulation to probation officers could be investigated
      further by comparing the process with formulation development by mental health
      experts with previously extensive formulation experience. Formulation will
      probably need to be adapted to meet the needs of the context in which it is
      developed. The relationship between formulation and management outcome was not
      investigated here and would be a further important step.

PMID- 24101408
TI  - Case formulation in personality disordered offenders: views from the front line.
AB  - BACKGROUND: Case formulation (CF) is a process that provides a psychological
      understanding of a person's difficulties and results in an intervention plan to
      address them. CF may be particularly useful in complex cases; yet the evidence
      base on its application in forensic settings is limited. Nevertheless, CF is a
      key part of the UK government's strategy for high-risk personality disordered
      offenders. As part of this strategy, probation staff are expected to carry out CF
      in order to inform interventions for these offenders. AIMS/HYPOTHESES: This study
      sought to access the experience of probation staff of working with personality
      disordered offenders and their views around their role in the strategy and what
      challenges and benefits might arise. METHODS: Three focus groups were carried
      out, each with 6-7 probation staff. RESULTS: Four themes emerged. Firstly, staff
      reported a lack of personality disorder (PD)-specific training, and the work that
      they do with PD offenders is hampered by this. Secondly, probation staff
      experience difficulties when attempting to obtain help for PD offenders,
      including diagnostic assessments and treatment for those already diagnosed.
      Thirdly, the work probation staff currently do with offenders covers similar
      areas as CF but with a different focus. Fourthly, participants welcomed the
      prospect of PD-specific training but were concerned that they should be
      appropriately supervised and not left to carry out work for which they feel under
      trained. CONCLUSIONS: Our findings point towards potential benefits in providing
      probation staff with PD-specific training in order to implement the PD offender
      strategy. IMPLICATIONS FOR PRACTICE: Issues relating to the lack of provision of
      appropriate treatment and the need for relevant supervision of probation staff
      conducting CF need to be addressed in order to enhance the successful operation
      of the strategy.

PMID- 24101409
TI  - The Index Offence Representation Scales; a predictive clinical tool in the
      management of dangerous, violent patients with personality disorder?
AB  - BACKGROUND: Forensic mental health professionals attach considerable importance
      to their patient's description of his or her index offence. Despite this, there
      is no systematic approach to examining and formulating the patient's offence
      narrative. AIM: To use the index offence narratives and capacity to mentalize of
      violent offender-patients with personality disorder to develop a tool to predict
      their progress and to evaluate that tool. METHOD: In a prospective, cohort study,
      the index offence narratives of 66 violent high security hospital patients with
      personality disorder were obtained from a semi-structured interview and used to
      generate the Index Offence Representational Scales (IORS). The predictive
      validity of these scales was investigated across a range of outcome variables,
      controlling for the association between initial and final value of the dependent
      variable. RESULTS: The degree to which patients held internal representations of
      interpersonal violence and malevolence, as measured by the IORS, predicted
      subsequent violent behaviour. In contrast to their actual aggressive behaviour,
      these patients rated themselves as having fewer symptoms on the Symptom Checklist
      90-R (SCL-90-R) and fewer problems in interpersonal relationships on the
      Inventory of Interpersonal Problems. A more empathic victim representation on the
      IORS predicted better engagement with treatment. CONCLUSIONS: The IORS show
      promise for helping clinicians formulate the early institutional pathway of
      seriously violent people with personality disorder, particularly with respect to
      their overt aggression and prosocial engagement. Replication studies are,
      however, indicated.

PMID- 24101410
TI  - Forensic case formulation: theoretical, ethical and practical issues.
AB  - ARGUMENT: Forensic case formulation, of increasing interest to practitioners and
      researchers raises many ethical, theoretical and practical issues for them.
      CONCLUSION: Systemic, contextual and individual factors which need to be
      considered include the multitude of staff often involved with any one individual,
      the pressure to 'get it right' because of the range of risk implications that are
      associated with individuals within forensic mental health settings, and
      individual parameters, for example reluctance to be engaged with services.

PMID- 24101411
TI  - Modulation of electroosmosis and flux through skin: effect of propylene glycol.
AB  - The effect of propylene glycol (PG) on transdermal flux under current was
      investigated using conventional in vitro iontophoresis methodology. The results
      were evaluated to explain how PG affects the electroosmotic volume flow (EVF) and
      electromigrational flux through skin. As a marker molecule for the direction and
      magnitude of EVF, a non-charged neutral molecule, acetaminophen (AAP), was used.
      At pH 7.4, the direction of EVF was from anode to cathode. During anodal and
      cathodal current application, PG decreased AAP flux and this decrease was
      proportional to the concentration of PG, indicating that the presence of PG in
      the medium decreased the EVF. This decrease is likely due to the decrease in
      dielectric constant of the medium and the increases in medium viscosity by the
      addition of PG. The increase in AAP solubility and the viscosity of the medium by
      PG may also contribute to the decrease in diffusional flux. The magnitude of EVF
      was estimated to be about 4.2 MUl/cm(2 )h. The effect of PG on the flux of a
      positively charged drug, donepezil hydrochloride (DH), was further investigated
      using pH 4.6 phosphate buffer solution. The permselectivity of skin in this
      solution was also investigated and revealed that the isoelectric point of
      hairless mouse skin is higher than pH 4.6. Anodal delivery showed much higher
      flux than cathodal and passive flux, indicating that electromigration is playing
      the major role for DH flux. As the concentration of PG increased, anodal flux of
      DH decreased. The main reason for this decrease in electromigration is likely due
      to the increase in medium viscosity. These results and discussions clearly
      suggest that the incorporation of frequently used organic cosolvents and
      penetration enhancers into the iontophoretic formulation should be carefully
      chosen with a thorough investigation for their effect on flux. Overall, these
      results provided further mechanistic insights into the role of electroosmosis and
      electromigration in flux across skin, and how they can be modulated by organic
      cosolvent, PG.

PMID- 24101412
TI  - The osmotic stress response of split influenza vaccine particles in an acidic
      environment.
AB  - Oral influenza vaccine provides an efficient means of preventing seasonal and
      pandemic disease. In this work, the stability of envelope-type split influenza
      vaccine particles in acidic environments has been investigated. Owing to the fact
      that hyper-osmotic stress can significantly affect lipid assembly of vaccine,
      osmotic stress-induced morphological change of split vaccine particles, in
      conjunction with structural change of antigenic proteins, was investigated by the
      use of stopped-flow light scattering (SFLS), intrinsic fluorescence, transmission
      electron microscopy (TEM), and hemagglutination assay. Split vaccine particles
      were found to exhibit a step-wise morphological change in response to osmotic
      stress due to double-layered wall structure. The presence of hyper-osmotic stress
      in acidic medium (0.3 osmolarity, pH 2.0) induced a significant level of membrane
      perturbation as measured by SFLS and TEM, imposing more damage to antigenic
      proteins on vaccine envelope than can be caused by pH-induced conformational
      change at acidic iso-osmotic condition. Further supports were provided by the
      intrinsic fluorescence and hemagglutinin activity measurements. Thus, hyper
      osmotic stress becomes an important factor for determining stability of split
      vaccine particles in acidic medium. These results are useful in better
      understanding the destabilizing mechanism of split influenza vaccine particles in
      gastric environment and in designing oral influenza vaccine formulations.

PMID- 24101413
TI  - Cardiac imaging in adults with congenital heart disease: unknowns and issues
      related to diagnosis.
AB  - OPINION STATEMENT: Many adults with simple and complex congenital heart disease
      (CHD) survive to adulthood. The goal of imaging is to diagnose the underlying
      anomalies and to detect late complications of their CHD and past surgical repair,
      in order to assess the need for further intervention and better prepare for
      endovascular or open-heart surgery. Cardiac magnetic resonance imaging (MRI) and
      computerized tomography (CT) are increasingly utilized in this patient
      population, due to the technical advances made to these modalities in the past
      decade regarding image acquisition and reconstruction, spatial and temporal
      resolution, and radiation dose reduction. Here, we aim to review the role of
      cardiac MR in initial diagnosis, pre-treatment planning and post-surgical follow
      up of adults with CHD, and to discuss the ancillary role of cardiac CT in these
      patients.

PMID- 24101414
TI  - Left atrium penetration and tamponade: a rare complication of right subclavian
      permanent dialysis catheter.

PMID- 24101415
TI  - Ultrasound probe modification to optimise ultrasound-guided peripheral vascular
      access.

PMID- 24101416
TI  - Low rate of bacteremia with a subcutaneously implanted central venous access
      device.
AB  - PURPOSE: Patients at long-term acute care hospitals (LTACs) are medically complex
      with multiple comorbidities and high rates of antibiotic and device use. The
      objective of the study was to analyze the incidence and rate of central line
      associated bloodstream infections (CLABSI) and the critical factors for patient
      care, management, placement and maintenance of the implanted central venous
      access device at this LTAC. METHODS: A 13-year retrospective chart review was
      performed comprising 191 medically complex patients with multiple comorbidities
      who had an implanted central line port. Information analyzed included (1) number
      of catheters; (2) number of patients; (3) number of catheter line days; (4)
      patient demographics; (5) port location; (6) admission diagnoses; (7) type,
      incidence and rate of catheter-related complications. RESULTS: The total number
      of catheter days was over 183,183 with a mean of 959 catheter days per patient.
      The mean rate of CLABSI was 0.087 per 1,000 days; incidence was less than 8% of
      patients with catheters. CONCLUSIONS: The study found a markedly lower rate of
      CLABSI than reported for other LTACs as well as intensive care units, over 14- to
      100-fold lower than other LTACs. The authors propose that standardized catheter
      placement with implementation of rigorous, prospective catheter care plans and a
      team approach to management were responsible for extremely low complication
      rates. These results can be extrapolated to different settings across the
      healthcare continuum.

PMID- 24101417
TI  - Efficacy of normal saline in the maintenance of the arterial lines in comparison
      to heparin flush: a comprehensive review of the literature.
AB  - PURPOSE: The aim of this study is to examine the efficacy of normal saline (0.9%
      sodium chloride) as a flush solution on patency of arterial lines in comparison
      to heparin flush. Data have been examined in various categories of specialty
      (medical, surgical, cardiac, burns, gynecology), frequency of flushes, strength
      and volume of flushes, continuous versus bolus, duration of each flush and
      patency incidence (range, <= 24 to >= 96 hours). The secondary aim focused on the
      incidences of reported heparin-induced thrombocytopenia (HIT type I and II).
      METHODS: A comprehensive review of the literature from 1951 to 2012. An
      electronic search of OVID, Medline, Embase, Cochrane, Scopus and CINAHL database
      in English language was conducted. The search was limited to adult subjects only.
      The following keywords were used: heparin flush, saline flush, 0.9% sodium
      chloride flush, arterial line and indwelling vascular line. A total of ten papers
      (n=10) were found eligible. RESULTS: The evidence suggests patency is feasible
      with both solutions but if longer duration of use (arterial line) is advocated,
      heparin is superior in the long term. Furthermore, heparin flush effects are dose
      dependent and require fewer numbers of flushes. In addition, no adverse effects
      were found with heparin flush solution. CONCLUSION: There is level 1 evidence to
      support heparin as a flush solution once the time frame exceeds 48 hours. In
      addition, there is level 1 evidence to suggest that heparin at higher doses and
      in continuous infusion has better patency incidence with no reports of HIT type
      II or I.

PMID- 24101418
TI  - Percutaneous ultrasound-guided central venous catheters: the lateral in-plane
      technique for internal jugular vein access.
AB  - PURPOSE: To describe the possible ultrasound guidance techniques for the
      insertion of central venous catheters (CVCs), with emphasis particularly to the
      lateral short axis in-plane technique. METHODS: Numerous articles have shown
      significant benefits of using ultrasound guidance for venous access. Two main
      approaches to vein puncture are available, when considering visualization of the
      needle during its entry into the vein under the ultrasound beam: in-plane and out
      of-plane, which can be combined with two types of vein visualization, placing the
      ultrasound probe on the vein long axis or short axis. RESULTS: Advantages and
      limitations in internal jugular vein (IJV) cannulation for long-term dialysis
      CVCs are described for the above-mentioned approaches and visualizations. The
      lateral short axis in-plane technique has virtually no limitations, ensuring most
      benefits. CONCLUSIONS: The lateral short axis in-plane technique should be
      considered the first-line technique for IJV cannulation.

PMID- 24101419
TI  - Distal ulnar-basilic fistula as the first hemodialysis access.
AB  - PURPOSE: A distal forearm ulnar-basilic (UB) arteriovenous fistula (AVF) can be
      chosen if a radial-cephalic (RC)-AVF is not suitable for a primary AVF. However,
      limited data are available on the feasibility of using a distal forearm UB-AVF as
      an option for primary AVF. METHODS: This retrospective analysis included 446
      patients for whom AVFs (417 RC and 29 UB) had been newly created from January
      2003 to December 2009, at our hospital. Patients in whom the arterial or venous
      anatomy precluded RC-AVF creation, UB-AVF was established as distally as possible
      on the forearm. Patency, defined as access survival after creation, was
      calculated using Kaplan-Meier analysis. The difference in patency between the two
      groups was examined using log-rank test. RESULTS: The primary patency of UB-AVFs
      was significantly lower than that of RC-AVFs (p=0.037, log-rank test). The
      primary patency rate at 1 year was 25.0% versus 44.7%, respectively. However,
      there was no significant difference in secondary patency between the two groups.
      The secondary patency rate at 1 year was 85.5% for UB-AVFs versus 82.9% for RC
      AVFs. The incidence rate of percutaneous angioplasty until access abandonment per
      patient-years was 1.100 for UB-AVFs versus 0.671 for RC-AVFs. There was no
      difference in the time to maturation between the two groups. CONCLUSIONS: The
      secondary patency rate of UB-AVF is similar to that of RC-AVF. We recommend the
      creation of an UB-AVF when an RC-AVF is not a suitable option for the primary
      AVF.

PMID- 24101421
TI  - Hemodialysis catheter-induced stroke.

PMID- 24101420
TI  - Very high-dose cholecalciferol and arteriovenous fistula maturation in ESRD: a
      randomized, double-blind, placebo-controlled pilot study.
AB  - PURPOSE: While vitamin D is critical for optimal skeletal health, it also appears
      to play a significant role in vascular homeostasis. This pilot study compared
      arteriovenous (AV) access outcomes following cholecalciferol supplementation
      compared to placebo in end-stage renal disease patients preparing to undergo AV
      access creation. METHODS: A total of 52 adult hemodialysis patients preparing for
      arteriovenous fistula (AVF) creation were randomized to receive perioperative
      high-dose cholecalciferol versus placebo in this double-blind, randomized,
      placebo-controlled pilot study. The primary outcome was mean response to high
      dose oral cholecalciferol versus placebo, and secondary outcome AV access
      maturation at 6 months. Logistic regression was used to assess the association
      between AV access maturation and baseline, posttreatment and overall change in
      vitamin D concentration. RESULTS: A total of 45% of cholecalciferol-treated and
      54% of placebo-treated patients were successfully using their AVF or
      arteriovenous graft (AVG) at 6 months (p=0.8). Baseline serum concentrations of
      25(OH)D and 1,25(OH)2D did not differ between those who experienced AVF or AVG
      maturation and those who did not (p=0.22 and 0.59, respectively). Similarly,
      there was no relationship between AVF or AVG maturation and posttreatment serum
      25(OH)D and 1,25(OH)2D concentration (p=0.24 and 0.51, respectively).
      CONCLUSIONS: Perioperative high-dose vitamin D3 therapy does correct 25(OH)D
      level but does not appear to have an association with AV access maturation rates.
      Future research may include extended preoperative vitamin D3 therapy in a larger
      population or in certain subpopulations at high risk for AVF failure.

PMID- 24101422
TI  - The role of ultrasound as an adjunct to arterial catheterization in critically
      ill surgical and intensive care unit patients.
AB  - OBJECTIVE: To review the evidence behind Ultrasound (US) guided placement of
      arterial cannulae and its use in the critically ill population. DATA SOURCES: We
      performed a computer-aided literature search using set search terms and
      electronic data bases of PubMed and EMBASE from their commencement date through
      the end of July 2013. SUMMARY OF REVIEW: Insertion of intra-arterial catheters is
      a commonly performed invasive procedure in the peri-operative and intensive care
      setting that facilitates invasive blood pressure and cardiac output monitoring as
      well as frequent blood sampling. Arterial catheterization can be particularly
      challenging in critically ill and high-risk surgical patients with circulatory
      collapse, low cardiac output state and peripheral edema, all of which can limit
      the ability to successfully palpate and cannulate the artery. There is a
      convincing body of evidence suggesting a decrease in complication rate and first
      pass success rate in US guided central venous catheter (CVC) insertion compared
      with the landmark technique. While most intensivists and peri-operative
      physicians are familiar with US guided CVC placement, fewer use US to guide
      arterial access. CONCLUSIONS: Most studies have demonstrated a higher success
      rate when using US guidance for arterial cannulation. Moreover, the technique
      permits more rapid access and establishment compared with the conventional
      palpation technique. However, there is evidence opposing the routine use of US to
      guide arterial cannula insertion. Further studies are required to ascertain the
      benefits and cost effectiveness of US guided arterial catheterization in peri
      operative and critical care.

PMID- 24101423
TI  - [Role of microglia in neuronal circuit formation].
AB  - Microglia are known to maintain the cellular environment in the brain via their
      phagocytic activity. Further, recent studies have demonstrated that microglia
      play an important role in neuronal circuit formation. During neuronal
      development, new axonal and dendritic processes are formed, but excessive
      connections are eliminated appropriately; microglia participate in this pruning
      process. Moreover, evidence shows that microglia contribute to synaptic
      maturation by secreting various molecules.

PMID- 24101424
TI  - [Brain development and glutamate].
AB  - The involvement of glutamate in early brain development has been somewhat
      controversial. A large body of in vitro evidences indicates that the
      neurotransmitter glutamate influences early developmental events such as
      proliferation, migration, and differentiation. Paradoxically, loss-of-function
      mouse models of glutamatergic signaling that are generated by genetic deletion of
      receptors or the process of glutamate release exhibit normal brain development.
      The absence of an effect following genetic disruption of glutamatergic signaling
      might reflect compensation from other neurotransmitters such as GABA and glycine,
      both of which can depolarize immature neurons similar to glutamate. To overcome
      this potential confusion, we examined the direct consequences of extracellular
      glutamate buildup on brain development by reducing the levels of glutamate
      transporters GLAST and GLT1. GLAST/GLT1 double knockout mice (DKO) exhibit
      multiple brain defects, including cortical, hippocampal, and amygdalar
      disorganization with perinatal mortality. Several essential aspects of neuronal
      development, such as stem cell proliferation, radial migration, and neuronal
      differentiation were impaired in these mutants. The deletion of N-methyl-D
      aspartate (NMDA) receptor 1 subunit in DKO mice almost completely rescued
      multiple brain defects. These results provide direct in vivo evidence that
      glutamatergic activity through NMDA receptors does indeed modulate early brain
      developmental processes.

PMID- 24101425
TI  - [Neuronal distribution in the cerebral cortex and its significance in
      schizophrenia].
AB  - Abnormal cortical architectures have been identified as one of the microscopic
      neuropathological findings of schizophrenia. Among such findings, the altered
      distribution of neurons is suggestive of deficits during brain development and is
      consistent with the neurodevelopmental hypothesis of schizophrenia. However, the
      relationship between altered neuronal distribution and emergence of psychosis is
      unclear. In this review, we discuss the neurodevelopmental hypothesis of
      schizophrenia and describe the normal architecture of the neocortex and the
      recent findings regarding neocortical development. Thereafter, we summarize the
      abnormal cortical architectures reported for the brains of patients with
      schizophrenia. Furthermore, on the basis of the recent findings regarding
      cortical development, we suggest a mechanism for the formation of abnormal
      cortical architectures in schizophrenia and speculate how it could relate to some
      of the symptoms of schizophrenia.

PMID- 24101426
TI  - [The female brain and the male brain].
AB  - Sex differences in the nervous system are prevalent throughout the animal
      kingdom. In humans, the corpus callosum and anterior commissure are larger in
      females, whereas some hypothalamic nuclei and associated structures are larger in
      males. Numerous studies in rodents have demonstrated that when these nuclei are
      exposed to circulating androgens during the critical period around birth, they
      develop into male-typical structures. In addition to this organizational effect,
      androgens exert an activational effect during adulthood. For example, sexually
      dimorphic gene expression in the hypothalamus and amygdala depends on circulating
      androgen levels. Cckar encodes a G protein-coupled receptor and its expression is
      sexually dimorphic. The major of Cckar-expressing neurons in the ventrolateral
      division of ventromedial hypothalamus (VMHvl) also express progesterone receptor
      (PR), with a female-biased expansion of arborizations in the anteroventral
      periventricular hypothalamic nucleus. Selective ablation of these PR-positive
      neurons in the VMHvl results in a marked reduction in female sexual receptivity
      and male aggression, demonstrating that these sexually dimorphic neurons
      contribute to gendered behavior in mammals. Remarkable sex differences in single
      neurons have been documented in the fruitfly (Drosophila melanogaster). The
      fruitless (fru) gene in the fruitfly is considered as a major regulator of male
      courtship circuitry; a male specific fru-expressing neuron cluster, P1, can
      initiate male courtship when artificially activated even in the absence of
      courtship target (e.g., a female). The fru gene encodes a set of putative
      transcription factors that appear to orchestrate the transcription of ~100 genes
      by recruiting chromatin regulators, histone deacetylase 1 or heterochromatin
      protein 1a, to the target sites. These studies have unraveled the causal link
      among genes, brain sexual dimorphisms and gendered behaviors.

PMID- 24101427
TI  - [Critical period mechanisms: implication for neurodevelopmental and psychiatric
      disorders].
AB  - Our behavior reflects the neural circuits sculpted by our experiences during
      early temporary windows of heightened brain plasticity called critical periods.
      Such heightened plasticity declines in adulthood, often limiting recovery of
      function. On the other hand, the adult brain also needs stability. Failed
      stabilization can disrupt circuit computations by allowing modification by
      undesirable information, which may lead to mental disorders. Understanding the
      mechanisms regulating the critical periods of neural plasticity can provide
      insights toward therapeutic interventions for neurodevelopmental and psychiatric
      disorders. In this review, we discuss the potential contributions of "molecular
      brakes" on the critical period plasticity in the visual system to the etiology of
      psychiatric disorders. Interestingly, recent findings for the pathophysiological
      changes associated with schizophrenia indicate excessive plasticity due to the
      removal of molecular brakes. Applying the mechanistic understandings of critical
      period plasticity in the visual system to cognitive development may provide a
      conceptual framework for exploring novel endophenotypes and therapeutic
      approaches to treat psychiatric disorders.

PMID- 24101428
TI  - [Molecular basis of long-lasting synaptic modifications underlying learning and
      memory].
AB  - Neurons make contact with each other and form neuronal networks. The synapse, the
      site of contact between 2 neurons, has the ability to dynamically modify
      functional efficiency and connectivity in response to spatially and temporally
      specific patterns of neuronal activity. Such plastic ability of the synapse is
      believed to be indispensable for our cognitive functions, including learning and
      memory. In this review, I summarize our current understanding of the molecular
      and cellular mechanisms underlying synaptic plasticity. Lines of evidence have
      indicated that postsynaptic regulations of AMPA-type glutamate receptors (AMPA
      Rs) are crucial for synaptic plasticity. Synaptic plasticity can be long-lasting
      if the local synaptic modifications interact with activity-dependent, newly
      synthesized plasticity-related molecules in the neuronal cell body. Recently, we
      found that the activity-regulated memory-related protein Arc is involved in
      synapse-specific regulation of AMPA-Rs. This Arc-dependent mechanism, together
      with other molecular mechanisms, possibly helps maintain the contrast of synaptic
      strength between strong and weak synapses, thus, promoting the formation of long
      term memory.

PMID- 24101429
TI  - [The DIAN study].
AB  - The DIAN study compared the pathophysiological markers between carriers and non
      carriers of mutation for autosomal dominant Alzheimer's disease (AD). They used
      the participant's age at baseline assessment and the parent's age at the onset of
      symptoms of AD to calculate the estimated delay in symptom onset. The study
      revealed that the biomarker change, which is the reduction of Abeta42 in the CSF
      of the carrier's brain, started approximately 15-20 years prior to the onset of
      symptoms. Subsequently, a chronological series of events took place: deposition
      of fibrillar Abeta as measured by positron emission tomography with the use of
      Pittsburgh compound B, increase in tau protein in the CSF, hippocampal atrophy
      and hypometabolism of FDG-PET, and cognitive and clinical changes. The
      researchers planned to start the prevention trial with 2 monoclonal antibodies
      and a BACE inhibitor. In contrast, the API study is the clinical trial of the
      anti-amyloid monoclonal antibody therapy associated with the early-onset familial
      AD (EOAD), which carries the PSEN1 E280A mutation. This study also showed changes
      in the same biomarker as reported in the DIAN study. Anti-amyloid treatment in
      asymptomatic AD (A4) is a prevention trial aimed at treating older individuals
      with normal cognition but at risk of developing AD dementia on the basis of
      having biomarker evidence of amyloid (preclinical AD). They selected solanezumab
      for the anti-amyloid treatment for A4.

PMID- 24101430
TI  - [Diagnosis and novel treatment approaches in restless legs syndrome: I.
      Pathophysiology and diagnosis].
AB  - Restless legs syndrome (RLS) is a clinically important, common disease and should
      be diagnosed and treated early and adequately. At present, there have been no
      clinical biomarkers or methodologies that can contribute to the correct diagnosis
      of RLS, RLS should be diagnosed on the basis of 4 essential criteria: urge to
      move the legs, improvement after movement, and worsening or occurrence of
      symptoms in the evening and at rest. When applying the criteria, RLS mimics
      should be ruled out and comorbid diseases should be taken into account. The
      origin and pathogenesis of RLS are still under investigation; however, iron
      deficiency in the brain has been observed on imaging and cerebrospinal fluid
      analyses of patients with RLS. In contrast, the results of neuroimaging studies
      evaluating brain dopaminergic functions in patients with RLS have yielded
      inconclusive results, although involvement of the hypothalamus (A11) is thought
      to cause impaired dopaminergic modulation in the dorsal horn and
      intermediolateral nucleus, resulting in the restlessness of legs.

PMID- 24101431
TI  - [A case of culture-negative brain abscess caused by Streptococcus intermedius
      infection diagnosed by broad-range PCR of 16S ribosomal RNA].
AB  - A 50-year-old man presented with altered mental status during hospitalization for
      pneumonia. MRI showed multifocal ring-enhanced lesions, which consisted of
      multiple cerebral abscesses. We started empirical antibiotic therapy, but the
      following morning, his condition rapidly deteriorated and a CT scan revealed
      acute hydrocephalus, which required ventricular drainage. Gram staining of
      cerebro-spinal fluid from the ventricular drainage showed gram-positive cocci in
      chains, but culture results were negative. 16S ribosomal RNA sequencing with
      broad-range PCR of the cerebro-spinal fluid identified Streptococcus intermedius.
      On the basis of this identification, the antibiotic regimen was changed to
      ampicillin monotherapy. After 1 year of antibiotic therapy, all the abscesses had
      disappeared and the patient was discharged without any sequelae. Bacterial 16S
      rRNA gene analysis with broad-range PCR is a very useful method for facilitating
      the etiological diagnosis and selection of appropriate treatment for culture
      negative infections.

PMID- 24101432
TI  - Thymoquinone prevents beta-amyloid neurotoxicity in primary cultured cerebellar
      granule neurons.
AB  - Thymoquinone (TQ), a bioactive constituent of Nigella sativa Linn (N. sativa) has
      demonstrated several neuropharmacological attributes. In the present study, the
      neuroprotective properties of TQ were investigated by studying its anti-apoptotic
      potential to diminish beta-amyloid peptide 1-40 sequence (Abeta1-40)-induced
      neuronal cell death in primary cultured cerebellar granule neurons (CGNs). The
      effects of TQ against Abeta1-40-induced neurotoxicity, morphological damages, DNA
      condensation, the generation of reactive oxygen species, and caspase-3, -8, and 
      9 activation were investigated. Pretreatment of CGNs with TQ (0.1 and 1 MUM) and
      subsequent exposure to 10 MUM Abeta1-40 protected the CGNs against the neurotoxic
      effects of the latter. In addition, the CGNs were better preserved with intact
      cell bodies, extensive neurite networks, a loss of condensed chromatin and less
      free radical generation than those exposed to Abeta1-40 alone. TQ pretreatment
      inhibited Abeta1-40-induced apoptosis of CGNs via both extrinsic and intrinsic
      caspase pathways. Thus, the findings of this study suggest that TQ may prevent
      neurotoxicity and Abeta1-40-induced apoptosis. TQ is, therefore, worth studying
      further for its potential to reduce the risks of developing Alzheimer's disease.

PMID- 24101433
TI  - The thermosensitive potassium channel TREK-1 contributes to coolness-evoked
      responses of Grueneberg ganglion neurons.
AB  - Neurons of the Grueneberg ganglion (GG) residing in the vestibule of the murine
      nose are activated by cool ambient temperatures. Activation of thermosensory
      neurons is usually mediated by thermosensitive ion channels of the transient
      receptor potential (TRP) family. However, there is no evidence for the expression
      of thermo-TRPs in the GG, suggesting that GG neurons utilize distinct mechanisms
      for their responsiveness to cool temperatures. In search for proteins that render
      GG neurons responsive to coolness, we have investigated whether TREK/TRAAK
      channels may play a role; in heterologous expression systems, these potassium
      channels have been previously found to close upon exposure to coolness, leading
      to a membrane depolarization. The results of the present study indicate that the
      thermosensitive potassium channel TREK-1 is expressed in those GG neurons that
      are responsive to cool temperatures. Studies analyzing TREK-deficient mice
      revealed that coolness-evoked responses of GG neurons were clearly attenuated in
      these animals compared with wild-type conspecifics. These data suggest that TREK
      1 channels significantly contribute to the responsiveness of GG neurons to cool
      temperatures, further supporting the concept that TREK channels serve as
      thermoreceptors in sensory cells. Moreover, the present findings provide the
      first evidence of how thermosensory GG neurons are activated by given temperature
      stimuli in the absence of thermo-TRPs. 

PMID- 24101434
TI  - Fully automatic segmentation of the femur from 3D-CT images using primitive shape
      recognition and statistical shape models.
AB  - PURPOSE: Femur segmentation is well established and widely used in computer
      assisted orthopedic surgery. However, most of the robust segmentation methods
      such as statistical shape models (SSM) require human intervention to provide an
      initial position for the SSM. In this paper, we propose to overcome this problem
      and provide a fully automatic femur segmentation method for CT images based on
      primitive shape recognition and SSM. METHOD: Femur segmentation in CT scans was
      performed using primitive shape recognition based on a robust algorithm such as
      the Hough transform and RANdom SAmple Consensus. The proposed method is divided
      into 3 steps: (1) detection of the femoral head as sphere and the femoral shaft
      as cylinder in the SSM and the CT images, (2) rigid registration between
      primitives of SSM and CT image to initialize the SSM into the CT image, and (3)
      fitting of the SSM to the CT image edge using an affine transformation followed
      by a nonlinear fitting. RESULTS: The automated method provided good results even
      with a high number of outliers. The difference of segmentation error between the
      proposed automatic initialization method and a manual initialization method is
      less than 1 mm. CONCLUSION: The proposed method detects primitive shape position
      to initialize the SSM into the target image. Based on primitive shapes, this
      method overcomes the problem of inter-patient variability. Moreover, the results
      demonstrate that our method of primitive shape recognition can be used for 3D SSM
      initialization to achieve fully automatic segmentation of the femur.

PMID- 24101436
TI  - Gestational weight gain, early pregnancy maternal adiposity distribution, and
      maternal hyperglycemia.
AB  - To estimate the effects of gestational weight gain (GWG), central adiposity and
      subcutaneous fat on maternal post-load glucose concentration, pregnant women [n =
      413, 62% black, 57% with pregravid body mass index (BMI) >=25] enrolled in a
      cohort study at <=13 weeks gestation. GWG was abstracted from medical records. In
      a sub-sample of women (n = 214), waist circumference (WC), and biceps and triceps
      skinfold thicknesses were measured at enrollment. At 24-28 weeks gestation, post
      load glucose concentration was measured using a 50-g 1-h oral glucose tolerance
      test. After adjustment for pre-pregnancy BMI, age, parity, race/ethnicity,
      smoking, marital status, annual family income, education, family history of
      diabetes, and gestational age of GDM screening, each 0.3-kg/week increase in
      weight in the first trimester was associated with a 2.2 (95% CI 0.1, 4.3)-mg/dl
      increase in glucose concentration. Each 8.6-mm increase in biceps skinfold
      thickness and each 11.7-mm increase in triceps skinfold thickness was associated
      with 4.3 (95% CI 0.2, 8.5)-mg/dl increase in maternal glucose, independent of BMI
      and other confounders. Neither GWG in the second trimester nor WC at <=13 weeks
      was significantly associated with glucose concentration after confounder
      adjustment. Independent of pre-pregnancy BMI, high early pregnancy GWG and
      maternal subcutaneous body fat may be positively associated with maternal glucose
      concentrations at 24-28 weeks.

PMID- 24101435
TI  - Evaluation of a novel electronic genetic screening and clinical decision support
      tool in prenatal clinical settings.
AB  - "The Pregnancy and Health Profile" (PHP) is a free prenatal genetic screening and
      clinical decision support (CDS) software tool for prenatal providers. PHP
      collects family health history (FHH) during intake and provides point-of-care
      risk assessment for providers and education for patients. This pilot study
      evaluated patient and provider responses to PHP and effects of using PHP in
      practice. PHP was implemented in four clinics. Surveys assessed provider
      confidence and knowledge and patient and provider satisfaction with PHP. Data on
      the implementation process were obtained through semi-structured interviews with
      administrators. Quantitative survey data were analyzed using Chi square test,
      Fisher's exact test, paired t tests, and multivariate logistic regression. Open
      ended survey questions and interviews were analyzed using qualitative thematic
      analysis. Of the 83% (513/618) of patients that provided feedback, 97% felt PHP
      was easy to use and 98% easy to understand. Thirty percent (21/71) of
      participating physicians completed both pre- and post-implementation feedback
      surveys [13 obstetricians (OBs) and 8 family medicine physicians (FPs)].
      Confidence in managing genetic risks significantly improved for OBs on 2/6
      measures (p values <=0.001) but not for FPs. Physician knowledge did not
      significantly change. Providers reported value in added patient engagement and
      reported mixed feedback about the CDS report. We identified key steps, resources,
      and staff support required to implement PHP in a clinical setting. To our
      knowledge, this study is the first to report on the integration of patient
      completed, electronically captured and CDS-enabled FHH software into primary
      prenatal practice. PHP is acceptable to patients and providers. Key to successful
      implementation in the future will be customization options and interoperability
      with electronic health records.

PMID- 24101437
TI  - Optimizing health and health care systems for children with special health care
      needs using the life course perspective.
AB  - To date, life course research in maternal and child health has largely focused on
      elucidating fetal and early life influences on adult health and less on promoting
      the health of children with special health care needs (CSHCN). Consideration of
      life course theory (LCT) for CSHCN is especially important given their increasing
      prevalence and comorbidity, their disproportionate vulnerability to weaknesses or
      instability in the health care system, and the growing evidence linking child and
      adult health and quality of life. In this commentary we seek to advance the
      consideration of LCT for CSHCN. We (1) briefly summarize key issues and the
      importance of a life course approach for CSHCN; (2) present illustrative findings
      from population-based cross-sectional data that serve to generate hypotheses that
      can be more rigorously examined when population-based longitudinal data become
      available; and (3) discuss the application of life course principles as a driving
      force in the continued implementation and improvement of integrated systems of
      care for CSHCN. 

PMID- 24101438
TI  - Some personal notes on role plays as an excellent teaching tool : commentary on
      "using and developing role plays in teaching aimed at preparing for social
      responsibility".
AB  - Role plays are extremely valuable tools to address different aspects of teaching
      social responsibility, because they allow students to "live through" complex
      ethical decision making dilemmas. While role plays are getting high marks from
      students because their entertainment value is high, their educational value
      depends on their closeness to students' work experience and the skills of the
      teacher in helping students comprehend the lessons they are meant to convey. 

PMID- 24101439
TI  - Early and late renal adverse effects after potentially nephrotoxic treatment for
      childhood cancer.
AB  - BACKGROUND: Great improvements in diagnostics and treatment for malignant disease
      in childhood have led to a major increase in survival. However, childhood cancer
      survivors (CCS) are at great risk for developing adverse effects caused by
      multimodal treatment for their malignancy. Nephrotoxicity is one of these known
      (acute) side effects of several treatments, including cisplatin, carboplatin,
      ifosfamide, radiotherapy and nephrectomy, and can cause glomerular filtration
      rate impairment, proteinuria, tubulopathy and hypertension. However, evidence
      about the long-term effects of these treatments on renal function remains
      inconclusive. To reduce the number of (long-term) nephrotoxic events in CCS, it
      is important to know the risk of, and risk factors for, early and late renal
      adverse effects, so that ultimately treatment and screening protocols can be
      adjusted. OBJECTIVES: To evaluate existing evidence on the effects of potentially
      nephrotoxic treatment modalities on the prevalence of and associated risk factors
      for renal dysfunction in survivors treated for childhood cancer with a median or
      mean survival of at least one year after cessation of treatment, where possible
      in comparison with healthy controls or CCS treated without potentially
      nephrotoxic treatment. SEARCH METHODS: We searched the following electronic
      databases: the Cochrane Central Register of Controlled Trials (CENTRAL) (The
      Cochrane Library, Issue 4, 2011), MEDLINE/PubMed (from 1945 to December 2011) and
      EMBASE/Ovid (from 1980 to December 2011). SELECTION CRITERIA: With the exception
      of case reports, case series and studies including fewer than 20 participants, we
      included studies with all study designs that reported on renal function (one year
      or longer after cessation of treatment) in children and adults who were treated
      for a paediatric malignancy (aged 18 years or younger at diagnosis) with
      cisplatin, carboplatin, ifosfamide, radiation including the kidney region and/or
      a nephrectomy. DATA COLLECTION AND ANALYSIS: Two review authors independently
      performed study selection, risk of bias assessment and data extraction using
      standardised data collection forms. Analyses were performed according to the
      guidelines of the Cochrane Handbook for Systematic Reviews of Interventions. MAIN
      RESULTS: The search strategy identified 5504 studies, of which 5138 were excluded
      on the basis of title and/or abstract. The full-text screening of the remaining
      366 articles resulted in the inclusion of 57 studies investigating the prevalence
      of and sometimes also risk factors for early and late renal adverse effects of
      treatment for childhood cancer. The 57 studies included at least 13,338
      participants of interest for this study, of whom at least 6516 underwent renal
      function testing. The prevalence of renal adverse effects ranged from 0% to 84%.
      This variation may be due to diversity in included malignancies, prescribed
      treatments, reported outcome measurements and the methodological quality of
      available evidence.Chronic kidney disease/renal insufficiency (as defined by the
      authors of the original studies) was reported in 10 of 57 studies. The prevalence
      of chronic kidney disease ranged between 0.5% and 70.4% in the 10 studies and
      between 0.5% and 18.8% in the six studies that specifically investigated Wilms'
      tumour survivors treated with a unilateral nephrectomy.A decreased (estimated)
      glomerular filtration rate was present in 0% to 50% of all assessed survivors
      (32/57 studies). Total body irradiation; concomitant treatment with
      aminoglycosides, vancomycin, amphotericin B or cyclosporin A; older age at
      treatment and longer interval from therapy to follow-up were significant risk
      factors reported in multivariate analyses. Proteinuria was present in 0% to 84%
      of all survivors (17/57 studies). No study performed multivariate analysis to
      assess risk factors for proteinuria.Hypophosphataemia was assessed in seven
      studies. Reported prevalences ranged between 0% and 47.6%, but four of seven
      studies found a prevalence of 0%. No studies assessed risk factors for
      hypophosphataemia using multivariate analysis. The prevalence of impairment of
      tubular phosphate reabsorption was mostly higher (range 0% to 62.5%; 11/57
      studies). Higher cumulative ifosfamide dose, concomitant cisplatin treatment,
      nephrectomy and longer follow-up duration were significant risk factors for
      impaired tubular phosphate reabsorption in multivariate analyses.Treatment with
      cisplatin and carboplatin was associated with a significantly lower serum
      magnesium level in multivariate analysis, and the prevalence of hypomagnesaemia
      ranged between 0% and 37.5% in the eight studies investigating serum
      magnesium.Hypertension was investigated in 24 of the 57 studies. Reported
      prevalences ranged from 0% to 18.2%. A higher body mass index was the only
      significant risk factor noted in more than one multivariate analysis. Other
      reported factors that significantly increased the risk of hypertension were use
      of total body irradiation, abdominal irradiation, acute kidney injury, unrelated
      or autologous stem cell donor type, growth hormone therapy and older age at
      screening. Previous infection with hepatitis C significantly decreased the risk
      of hypertension.Because of the profound heterogeneity of the studies, it was not
      possible to perform any meta-analysis. AUTHORS' CONCLUSIONS: The prevalence of
      renal adverse events after treatment with cisplatin, carboplatin, ifosfamide,
      radiation therapy involving the kidney region and/or nephrectomy ranged from 0%
      to 84%. With currently available evidence, it was not possible to draw any
      conclusions with regard to prevalence of and risk factors for renal adverse
      effects. Future studies should focus on adequate study design and reporting and
      should deploy multivariate risk factor analysis to correct for possible
      confounding. Until more evidence becomes available, CCS should be enrolled into
      long-term follow-up programmes to monitor their renal function and blood
      pressure.

PMID- 24101440
TI  - Cloning of a new fibroblast cell line from an early primary culture from mandarin
      fish (Siniperca chuatsi) fry for efficient proliferation of megalocytiviruses.
AB  - Megalocytiviruses are important emerging pathogens in both freshwater and marine
      finfish aquaculture. However, a limited number of piscine cell lines are
      persistently susceptible to these viruses, which greatly limits the study of
      megalocytiviruses. In this study, a new fibroblast-like cell line was established
      from an early primary culture from mandarin fish fry by a single cell cloning and
      was designated as MFF-8C1. The MFF-8C1 cells grow well in Dulbecco's modified
      Eagle's medium supplemented with 10 % fetal bovine serum and had been subcultured
      more than 60 passages since the initial recovery culture in October 2009.
      Chromosomal analysis revealed that 91 % of the MFF-8C1 cells maintained a normal
      diploid chromosome number (2n = 48) in the 46th passage. Infection experiments
      showed that both freshwater-borne and marine-borne megalocytiviruses induce
      severe cytopathic effects in infected MFF-8C1 cells characterized by the rounding
      and enlargement of cells, which are highly consistent with the previous
      description of the infection in other susceptible cells with megalocytivirus.
      Megalocytivirus infections were further confirmed by a transmission electron
      microscopy. Furthermore, the MFF-8C1-cultured megalocytiviral suspension was
      highly virulent to infected mandarin fish. In summary, a new fibroblast cell line
      from mandarin fish fry that was highly permissive to megalocytiviruses was
      established. The MFF-8C1 cell line is a promising cellular substrate candidate
      for cell-cultured vaccine production of megalocytivirus. 

PMID- 24101441
TI  - Cytogenetic, cytotoxic and GC-MS studies on concrete and absolute oils from Taif
      rose, Saudi Arabia.
AB  - Taif rose (Rosa damascena trigintipetala Dieck) is a sort of damask rose, which
      is considered as one of the most important economic products of Taif. In this
      study, the authors investigated the possible cytotoxic, genotoxic, antimutagenic
      and anticancer effect of concrete and absolute rose oils. The results showed that
      both concrete and absolute rose oils were cytotoxically and genotoxically safe at
      a dose of 10 MUg/ml when tested on cultures of normal human blood lymphocytes.
      Also, the results showed significant antimutagenic activity at p < 0.001 for
      absolute rose oil at the same dose level when tested on cultures of normal human
      blood lymphocytes supplemented with 300 ng/ml mitomycin C (MMC). On the other
      hand, concrete and absolute oils exerted a cytotoxic activity against two kinds
      of human cancer cell lines: HepG2 and MCF7. Concrete oil showed cytotoxic
      activity against HepG2 and MCF7 with a half maximal inhibitory concentration
      (IC50) of 16.28 and 18.09 MUg/ml, respectively, whereas absolute rose oil showed
      its cytotoxic activity against HepG2 and MCF7 with an IC50 of 24.94 and 19.69,
      respectively. From this study, it is concluded that concrete and absolute rose
      oils are cytotoxically and genotoxically safe at a dose of 10 MUg/ml when tested
      on cultures of normal human blood lymphocytes. In addition, absolute oil has an
      antimutagenic activity at the same dose. Further investigations are needed to
      study the activity of higher doses of both oils in vitro and in vivo in
      experimental animals in order to evaluate the capability of using these oils as
      therapeutic for treatment of some kinds of cancers. 

PMID- 24101442
TI  - Activation of J774.1 murine macrophages by lactate dehydrogenase.
AB  - We have already reported that lactate dehydrogenase (LDH) activates lymphocytes
      in vitro and in vivo. In this paper, we report the activating effects of LDH on
      the macrophage-like cell line J774.1. LDH was found to enhance production of IL-6
      and TNF-alpha by J774.1 cells in a dose-dependent manner. Transcription levels of
      IL-6 and TNF-alpha in J774.1 cells were also enhanced by supplementation with
      LDH. From immunoblot analysis, it was revealed that LDH enhances the
      phosphorylation level of JNK in J774.1 cells. Moreover, the JNK inhibitor
      SP600125 decreased production of IL-6 and TNF-alpha induced by LDH. NF-kappaB
      translocation to the nucleus was also facilitated by LDH. These results was
      revealed that LDH enhances production of IL-6 and TNF-alpha by J774.1 cells via
      the increase of JNK phosphorylation and NF-kappaB translocation to the nucleus.
      Our data indicated that macrophages may be activated by LDH released from damaged
      tissues and cells in our body. 

PMID- 24101443
TI  - A new non-enzymatic method for isolating human intervertebral disc cells
      preserves the phenotype of nucleus pulposus cells.
AB  - Cells isolated from intervertebral disc (IVD) tissues of human surgical samples
      are one of potential sources for the IVD cellular therapy. The purpose of this
      study was to develop a new non-enzymatic method, "tissue incubation", for
      isolating human IVD cells. The IVD tissues of annulus fibrosus (AF) and nucleus
      pulposus (NP) were incubated separately in tissue culture flasks with culture
      medium. After 7-10 days incubation, cells were able to migrate out of IVD tissues
      and proliferate in vitro. After 3-4 weeks culture, expanded cells were harvested
      by trypsinization, and the remaining tissues were transferred to a new flask for
      another round of incubation. The molecular phenotype of IVD cells from juvenile
      and adult human samples was evaluated by both flow cytometry analysis and
      immunocytochemical staining for the expression of protein markers of NP cells
      (CD24, CD54, CD239, integrin alpha6 and laminin alpha5). Flow cytometry confirmed
      that both AF and NP cells of all ages positively expressed CD54 and integrin
      alpha6, with higher expression levels in NP cells than in AF cells for the
      juvenile group sample. However, CD24 expression was only found in juvenile NP
      cells, and not in AF or older disc cells. Similar expression patterns for NP
      markers were also confirmed by immunocytochemistry. In summary, this new non
      enzymatic tissue incubation method for cell isolation preserves molecular
      phenotypic markers of NP cells and may provide a valuable cell source for the
      study of NP regeneration strategies. 

PMID- 24101444
TI  - Vascular biomechanical properties in mice with smooth muscle specific deletion of
      Ndst1.
AB  - Heparan sulfate proteoglycans act as co-receptors for many chemokines and growth
      factors. The sulfation pattern of the heparan sulfate chains is a critical
      regulatory step affecting the binding of chemokines and growth factors. N
      deacetylase-N-sulfotransferase1 (Ndst1) is one of the first enzymes to catalyze
      sulfation. Previously published work has shown that HSPGs alter tangent moduli
      and stiffness of tissues and cells. We hypothesized that loss of Ndst1 in smooth
      muscle would lead to significant changes in heparan sulfate modification and the
      elastic properties of arteries. In line with this hypothesis, the axial tangent
      modulus was significantly decreased in aorta from mice lacking Ndst1 in smooth
      muscle (SM22alphacre(+)Ndst1(-/-), p < 0.05, n = 5). The decrease in axial
      tangent modulus was associated with a significant switch in myosin and actin
      types and isoforms expressed in aorta and isolated aortic vascular smooth muscle
      cells. In contrast, no changes were found in the compliance of smaller
      thoracodorsal arteries of SM22alphacre(+)Ndst1(-/-) mice. In summary, the major
      findings of this study were that targeted ablation of Ndst1 in smooth muscle
      cells results in altered biomechanical properties of aorta and differential
      expression of myosin and actin types and isoforms.

PMID- 24101446
TI  - Enucleation of pancreatic lesions: indications, outcomes, and risk factors for
      clinical pancreatic fistula.
AB  - BACKGROUND: There are few large samples and single-center series that focus on
      the outcomes of pancreatic enucleation and risk factors for clinical pancreatic
      fistula (PF). This study aimed to evaluate the indications, short- and long-term
      results, and risk factors for clinical PF after pancreatic enucleation. METHODS:
      Patients who underwent pancreatic enucleation from January 2005 to April 2011 at
      the Peking Union Medical College Hospital in China were included. Clinical data
      were collected and analyzed. RESULTS: A total of 119 patients underwent
      enucleation. PF was the most common complication; the incidence of clinical PF
      (grades B and C) was 27.7 %. The most common indications were endocrine neoplasms
      (76.5 %). During a median follow-up of 41 months, no patient developed exocrine
      insufficiency. Three elderly patients developed non-insulin-dependent diabetes
      mellitus. One patient with VIPoma developed recurrence and liver metastasis. New
      York Heart Association (NYHA) class II or III (P = 0.009; hazard ratio (HR)
      3.191; 95 % confidence interval (CI) 1.334-7.632), operative time >=180 min (P =
      0.025; HR 2.664; 95 % CI 1.112-6.386) were the independent risk factors for
      clinical PF. CONCLUSION: Enucleation is a safe and effective treatment for benign
      and low malignant lesions of the pancreas. NYHA class II or III and operation
      time of >=180 min are independent risk factors for clinical PF.

PMID- 24101445
TI  - IFN-gamma (+874) and not TNF-alpha (-308) is associated with HBV-HCC risk in
      India.
AB  - Tumor necrosis factor (TNF)-alpha and interferon (IFN)-gamma, the pro
      inflammatory Th1 cytokines are the indispensable coordinators of the inflammatory
      responses involved in hepatitis B virus (HBV) pathogenesis. This study attempted
      to evaluate any possible association among TNF-alpha (-308G>A) and IFN-gamma
      (+874T/A) genotypes, the spontaneous blood and mRNA levels and expression of
      their major signal transducers, namely STAT1 and NF-kB with hepatitis B virus
      induced hepatocellular carcinoma (HCC) susceptibility in India. For this, 398
      subjects (146 controls, 68 inactive-HBV-carriers, 64 chronic-active HBV patients,
      61 HBV-cirrhotics, and 59 HBV-HCC subjects) were enrolled. Polymerase chain
      reaction-restriction fragment length polymorphism, allele-specific PCR, enzyme
      linked immunosorbent assay, reverse transcriptase-PCR, and Western blot analysis
      were done for assessing polymorphism, blood levels, mRNA expression, and protein
      expression of signal transducers, respectively, of TNF-alpha and IFN-gamma. The
      study revealed no significant association of TNF-alpha (-308) GA genotype, while
      a significant negative association of IFN-gamma (+874) TA and AA genotypes, in
      HBV-HCC risk. Moreover, blood levels of TNF-alpha were significantly elevated as
      disease progresses to HCC, while IFN-gamma levels were raised in HCC patients
      only. Besides, IFN-gamma mRNA levels were significantly elevated in cirrhotics,
      with no change observed in TNF-alpha transcript levels. Moreover, NF-kB
      expression also consistently increased during HCC progression. These observations
      suggest a vital negative association of IFN-gamma (+874) with HBV-HCC risk, with
      no significant association evident in TNF-alpha (-308). However, the TNF-alpha
      and IFN-gamma levels markedly increased in HCC development.

PMID- 24101447
TI  - Nonfunctional pancreatic neuroendocrine tumors <2 cm on preoperative imaging are
      associated with a low incidence of nodal metastasis and an excellent overall
      survival.
AB  - BACKGROUND: The optimal surgical management of small nonfunctional pancreatic
      neuroendocrine tumors (NF-PNETs) remains controversial. We sought to identify (1)
      clinicopathologic factors associated with survival in NF-PNETs and (2)
      preoperative tumor characteristics that can be used to determine which lesions
      require resection and lymph node (LN) harvest. METHODS: The records of all 116
      patients who underwent resection for NF-PNETs between 1989 and 2012 were reviewed
      retrospectively. Preoperative factors, operative data, pathology, surgical
      morbidity, and survival were analyzed. RESULTS: The overall 5- and 10-year
      survival rates were 83.9 and 72.8 %, respectively. Negative LNs (p = 0.005), G1
      or G2 histology (p = 0.033), and age <60 years (p = 0.002) correlated with better
      survival on multivariate analysis. The 10-year survival rate was 86.6 % for LN
      negative patients (n = 73) and 34.1 % for LN-positive patients (n = 32). Tumor
      size >=2 cm on preoperative imaging predicted nodal positivity with a sensitivity
      of 93.8 %. Positive LNs were found in 38.5 % of tumors >=2 cm compared to only
      7.4 % of tumors <2 cm. CONCLUSIONS: LN status, a marker of systemic disease, was
      a highly significant predictor of survival in this series. Tumor size on
      preoperative imaging was predictive of nodal disease. Thus, it is reasonable to
      consider parenchyma-sparing resection or even close observation for NF-PNETs <2
      cm.

PMID- 24101448
TI  - Reoperative intervention in patients with mesh at the hiatus is associated with
      high incidence of esophageal resection--a single-center experience.
AB  - BACKGROUND: Mesh hiatoplasty is a widely debated topic among foregut surgeons.
      While short-term outcomes tout decreased recurrence rates, an increase in mesh
      related complications has been reported. The aim of this study is to present a
      single-center experience with reoperative intervention in patients with previous
      mesh at the hiatus. METHODS: After institutional review board approval, a
      prospectively maintained database was retrospectively queried to identify
      patients who underwent reoperative intervention between 2003 and spring of 2013
      and had mesh placed at a previous hiatal hernia procedure. Patient charts were
      reviewed and data variables collected. RESULTS: Twenty-six patients (mean age of
      56.7 +/- 18.3; 19 females) who underwent 27 procedures met the inclusion
      criteria. Synthetic mesh was placed in 15 (56 %) procedures, while the remaining
      12 had biologic mesh. The mean interval between reoperative intervention and
      previous surgery was 33 months. Dysphagia (56 %) was the most common
      presentation, while three patients had mesh erosion. Recurrent hiatus hernia (2
      to 7 cm) was noted in 19 (70 %) patients. Eight patients (30 %) underwent redo
      fundoplication, six patients (22 %) were converted to Roux-en-Y
      gastrojejunostomy, two patients (7.4 %) underwent distal esophagectomy with
      esophagojejunostomy, five patients (19 %) had subtotal esophagectomy with gastric
      pull-up, and one patient underwent substernal gastric pull-up for esophageal
      bypass with interval esophagectomy. The mean operative time was 252 +/- 71.7 min,
      and the median blood loss was 150 ml (range, 50-1,650 ml). There was no
      postoperative mortality. CONCLUSION: Reoperative intervention in patients with
      mesh at the hiatus is associated with a high need for esophageal resection. More
      than two thirds of the patients also had a recurrent hiatal hernia.

PMID- 24101449
TI  - Influence of ethnicity on the efficacy and utilization of bariatric surgery in
      the USA.
AB  - BACKGROUND: Ethnic disparities in patterns of utilization and outcomes after Roux
      en-Y gastric bypass surgery (RYGB) were examined from Bariatric Outcomes
      Longitudinal Database. METHODS: Descriptive statistics were used for demographics
      of Whites, Blacks, or Hispanics undergoing RYGB with 1 year of follow-up, between
      June 2007 and October 2011. Multivariate logistic and normal regression models,
      controlling for baseline characteristics, examined relationships between race and
      outcomes. T tests were used for continuous variables and Pearson chi-square test
      for categorical variables. RESULTS: Study patients (108,333) were79 % White, 12 %
      Black, and 9 % Hispanic. Fewer Black males underwent surgery (15 %) compared to
      Whites or Hispanics (~22 %). Blacks compared to Whites were younger (42.7 +/-
      10.6 vs. 46.4 +/- 11.6 years), heavier BMI (50 +/- 9.1 vs. 47.4 +/- 8.0 kg/m(2)),
      and more often hypertensive (57 vs. 52 %). Other comorbidities were higher in
      Whites. Thirty-day mortality rate was equivalent (0.23-0.26 %), but serious
      adverse events were higher for Blacks (3.65 %) versus Whites (3.19 %) and
      Hispanics (2.01 %). At 1 year, weight and comorbidity burden declined
      significantly but less in Blacks despite adjustment for baseline characteristics.
      CONCLUSIONS: Fewer Black males underwent RYGB. Despite a smaller percent decline
      in BMI and comorbidities in Blacks, all races benefitted significantly from RYGB.
      Influence of other factors such as diet, culture, and genetics needs to be
      investigated further.

PMID- 24101450
TI  - Defining high risk: cost-effectiveness of extended-duration thromboprophylaxis
      following major oncologic abdominal surgery.
AB  - PURPOSE: Extended-duration thromboprophylaxis (EDTPPX) is the practice of
      prescribing antithrombotic therapy for 21 days after discharge, commonly used in
      surgical patients who are at high risk for venothromboembolism (VTE). While
      guidelines recommend EDTPPX, criteria are vague due to a paucity of data. The
      criteria can be further informed by cost-effectiveness thresholds. This study
      sought to determine the VTE incidence threshold for the cost-effectiveness of
      EDTPPX compared to inpatient prophylaxis. METHODS: A decision tree was used to
      compare EDTPPX for 21 days after discharge to 7 days of inpatient prophylaxis
      with base case assumptions based on an abdominal oncologic resection without
      complications in an otherwise healthy individual. Willingness to pay was set at
      $50,000/quality-adjusted life year (QALY). Sensitivity analyses were performed to
      assess uncertainty within the model, with particular interest in the threshold
      for cost-effectiveness based on VTE incidence. RESULTS: EDTPPX was the dominant
      strategy when VTE probability exceeds 2.39 %. Given a willingness to pay
      threshold of $50,000/QALY, EDTPPX was the preferred strategy when VTE incidence
      exceeded 1.22 and 0.88 % when using brand name or generic medication costs,
      respectively. CONCLUSIONS: EDTPPX should be recommended whenever VTE incidence
      exceeds 2.39 %. When post-discharge estimated VTE risk is 0.88-2.39 %, patient
      preferences about self-injections and medication costs should be considered.

PMID- 24101451
TI  - Internal hernia after laparoscopic Roux-en-Y gastric bypass.
AB  - BACKGROUND: The goal of this study was to determine the impact of mesenteric
      defect closure and Roux limb position on the rate of internal hernia after
      laparoscopic Roux-en-Y gastric bypass (LRYGB). METHODS: A retrospective review
      was conducted of all LRYGB patients from 2001 to 2011 who had all internal hernia
      (IH) defects closed (DC) or all defects not closed (DnC). RESULTS: Of 914
      patients, 663 (72.5 %) had DC vs. 251 (27.5 %) with DnC, and 679 (74.3 %) had an
      ante-colic vs. 235 (25.7 %) with a retro-colic Roux limb. Forty-six patients (5
      %) developed a symptomatic IH. Of these, 25 (3.8 %) were in the DC vs. 21 (8.4 %)
      in the DnC group (p = 0.005), and 26 (3.8 %) were in the ante-colic vs. 20 (8.5
      %) in the retro-colic Roux limb position (p = 0.005). Data from 45 patients were
      available for further analysis. The most common symptom was chronic postprandial
      abdominal pain (53.4 %). All patients underwent CT scan consistent with IH in 26
      patients (57.5 %), suggestive in 7 (15.6 %), showing small bowel obstruction in 4
      (8.9 %), and negative in 8 (17.8 %). CONCLUSIONS: Closure of mesenteric defects
      and ante-colic Roux limb position result in a significantly lower IH rate.
      Furthermore, a high index of suspicion must be maintained since symptoms may be
      nonspecific and imaging may be negative in nearly 20 % of patients.

PMID- 24101452
TI  - The evolution of the Faculty of Language from a Chomskyan perspective: bridging
      linguistics and biology.
AB  - While language was traditionally considered a purely cultural trait, the advent
      of Noam Chomsky's Generative Grammar in the second half of the twentieth century
      dramatically challenged that view. According to that theory, language is an
      innate feature, part of the human biological endowment. If language is indeed
      innate, it had to biologically evolve. This review has two main objectives:
      firstly, it characterizes from a Chomskyan perspective the evolutionary processes
      by which language could have come into being. Secondly, it proposes a new method
      for interpreting the archaeological record that radically differs from the usual
      types of evidence Paleoanthropology has concentrated on when dealing with
      language evolution: while archaeological remains have usually been regarded from
      the view of the behavior they could be associated with, the paper will consider
      archaeological remains from the view of the computational processes and
      capabilities at work for their production. This computational approach,
      illustrated with a computational analysis of prehistoric geometric engravings,
      will be used to challenge the usual generative thinking on language evolution,
      based on the high specificity of language. The paper argues that the biological
      machinery of language is neither specifically linguistic nor specifically human,
      although language itself can still be considered a species-specific innate trait.
      From such a view, language would be one of the consequences of a slight
      modification operated on an ancestral architecture shared with vertebrates. 

PMID- 24101453
TI  - Connectivity and cognition in autism spectrum disorders: where are the links?

PMID- 24101454
TI  - Does model-free forecasting really outperform the true model?

PMID- 24101455
TI  - Sperm competition drives the evolution of suicidal reproduction in mammals.
AB  - Suicidal reproduction (semelparity) has evolved in only four genera of mammals.
      In these insectivorous marsupials, all males die after mating, when failure of
      the corticosteroid feedback mechanism elevates stress hormone levels during the
      mating season and causes lethal immune system collapse (die-off). We
      quantitatively test and resolve the evolutionary causes of this surprising and
      extreme life history strategy. We show that as marsupial predators in Australia,
      South America, and Papua New Guinea diversified into higher latitudes, seasonal
      predictability in abundance of their arthropod prey increased in multiple
      habitats. More-predictable prey peaks were associated with shorter annual
      breeding seasons, consistent with the suggestion that females accrue fitness
      benefits by timing peak energy demands of reproduction to coincide with maximum
      food abundance. We demonstrate that short mating seasons intensified reproductive
      competition between males, increasing male energy investment in copulations and
      reducing male postmating survival. However, predictability of annual prey cycles
      alone does not explain suicidal reproduction, because unlike insect abundance,
      peak ovulation dates in semelparous species are often synchronized to the day
      among years, triggered by a species-specific rate of change of photoperiod. Among
      species with low postmating male survival, we show that those with suicidal
      reproduction have shorter mating seasons and larger testes relative to body size.
      This indicates that lethal effort is adaptive in males because females escalate
      sperm competition by further shortening and synchronizing the annual mating
      period and mating promiscuously. We conclude that precopulatory sexual selection
      by females favored the evolution of suicidal reproduction in mammals. 

PMID- 24101456
TI  - Mammalian cells preferentially internalize hydrogel nanodiscs over nanorods and
      use shape-specific uptake mechanisms.
AB  - Size, surface charge, and material compositions are known to influence cell
      uptake of nanoparticles. However, the effect of particle geometry, i.e., the
      interplay between nanoscale shape and size, is less understood. Here we show that
      when shape is decoupled from volume, charge, and material composition, under
      typical in vitro conditions, mammalian epithelial and immune cells preferentially
      internalize disc-shaped, negatively charged hydrophilic nanoparticles of high
      aspect ratios compared with nanorods and lower aspect-ratio nanodiscs.
      Endothelial cells also prefer nanodiscs, however those of intermediate aspect
      ratio. Interestingly, unlike nanospheres, larger-sized hydrogel nanodiscs and
      nanorods are internalized more efficiently than their smallest counterparts.
      Kinetics, efficiency, and mechanisms of uptake are all shape-dependent and cell
      type-specific. Although macropinocytosis is used by both epithelial and
      endothelial cells, epithelial cells uniquely internalize these nanoparticles
      using the caveolae-mediated pathway. Human umbilical vein endothelial cells, on
      the other hand, use clathrin-mediated uptake for all shapes and show
      significantly higher uptake efficiency compared with epithelial cells. Using
      results from both upright and inverted cultures, we propose that nanoparticle
      internalization is a complex manifestation of three shape- and size-dependent
      parameters: particle surface-to-cell membrane contact area, i.e., particle-cell
      adhesion, strain energy for membrane deformation, and sedimentation or local
      particle concentration at the cell membrane. These studies provide a fundamental
      understanding on how nanoparticle uptake in different mammalian cells is
      influenced by the nanoscale geometry and is critical for designing improved
      nanocarriers and predicting nanomaterial toxicity. 

PMID- 24101457
TI  - Pore waters regulate ion permeation in a calcium release-activated calcium
      channel.
AB  - The recent crystal structure of Orai, the pore unit of a calcium release
      activated calcium (CRAC) channel, is used as the starting point for molecular
      dynamics and free-energy calculations designed to probe this channel's conduction
      properties. In free molecular dynamics simulations, cations localize
      preferentially at the extracellular channel entrance near the ring of Glu
      residues identified in the crystal structure, whereas anions localize in the
      basic intracellular half of the pore. To begin to understand ion permeation, the
      potential of mean force (PMF) was calculated for displacing a single Na(+) ion
      along the pore of the CRAC channel. The computed PMF indicates that the central
      hydrophobic region provides the major hindrance for ion diffusion along the
      permeation pathway, thereby illustrating the nonconducting nature of the crystal
      structure conformation. Strikingly, further PMF calculations demonstrate that the
      mutation V174A decreases the free energy barrier for conduction, rendering the
      channel effectively open. This seemingly dramatic effect of mutating a nonpolar
      residue for a smaller nonpolar residue in the pore hydrophobic region suggests an
      important role for the latter in conduction. Indeed, our computations show that
      even without significant channel-gating motions, a subtle change in the number of
      pore waters is sufficient to reshape the local electrostatic field and modulate
      the energetics of conduction, a result that rationalizes recent experimental
      findings. The present work suggests the activation mechanism for the wild-type
      CRAC channel is likely regulated by the number of pore waters and hence pore
      hydration governs the conductance. 

PMID- 24101458
TI  - Cellular organization of cortical barrel columns is whisker-specific.
AB  - The cellular organization of the cortex is of fundamental importance for
      elucidating the structural principles that underlie its functions. It has been
      suggested that reconstructing the structure and synaptic wiring of the elementary
      functional building block of mammalian cortices, the cortical column, might
      suffice to reverse engineer and simulate the functions of entire cortices. In the
      vibrissal area of rodent somatosensory cortex, whisker-related "barrel" columns
      have been referred to as potential cytoarchitectonic equivalents of functional
      cortical columns. Here, we investigated the structural stereotypy of cortical
      barrel columns by measuring the 3D neuronal composition of the entire vibrissal
      area in rat somatosensory cortex and thalamus. We found that the number of
      neurons per cortical barrel column and thalamic "barreloid" varied substantially
      within individual animals, increasing by ~2.5-fold from dorsal to ventral
      whiskers. As a result, the ratio between whisker-specific thalamic and cortical
      neurons was remarkably constant. Thus, we hypothesize that the cellular
      architecture of sensory cortices reflects the degree of similarity in sensory
      input and not columnar and/or cortical uniformity principles. 

PMID- 24101459
TI  - Phagocytosis executes delayed neuronal death after focal brain ischemia.
AB  - Delayed neuronal loss and brain atrophy after cerebral ischemia contribute to
      stroke and dementia pathology, but the mechanisms are poorly understood.
      Phagocytic removal of neurons is generally assumed to be beneficial and to occur
      only after neuronal death. However, we report herein that inhibition of
      phagocytosis can prevent delayed loss and death of functional neurons after
      transient brain ischemia. Two phagocytic proteins, Mer receptor tyrosine kinase
      (MerTK) and Milk fat globule EGF-like factor 8 (MFG-E8), were transiently up
      regulated by macrophages/microglia after focal brain ischemia in vivo.
      Strikingly, deficiency in either protein completely prevented long-term
      functional motor deficits after cerebral ischemia and strongly reduced brain
      atrophy as a result of inhibiting phagocytosis of neurons. Correspondingly, in
      vitro glutamate-stressed neurons reversibly exposed the "eat-me" signal
      phosphatidylserine, leading to their phagocytosis by microglia; this neuronal
      loss was prevented in the absence of microglia and reduced if microglia were
      genetically deficient in MerTK or MFG-E8, both of which mediate
      phosphatidylserine-recognition. Thus, phagocytosis of viable neurons contributes
      to brain pathology and, surprisingly, blocking this process is strongly
      beneficial. Therefore, inhibition of specific phagocytic pathways may present
      therapeutic targets for preventing delayed neuronal loss after transient cerebral
      ischemia. 

PMID- 24101461
TI  - Passive energy recapture in jellyfish contributes to propulsive advantage over
      other metazoans.
AB  - Gelatinous zooplankton populations are well known for their ability to take over
      perturbed ecosystems. The ability of these animals to outcompete and functionally
      replace fish that exhibit an effective visual predatory mode is counterintuitive
      because jellyfish are described as inefficient swimmers that must rely on direct
      contact with prey to feed. We show that jellyfish exhibit a unique mechanism of
      passive energy recapture, which is exploited to allow them to travel 30% further
      each swimming cycle, thereby reducing metabolic energy demand by swimming
      muscles. By accounting for large interspecific differences in net metabolic
      rates, we demonstrate, contrary to prevailing views, that the jellyfish (Aurelia
      aurita) is one of the most energetically efficient propulsors on the planet,
      exhibiting a cost of transport (joules per kilogram per meter) lower than other
      metazoans. We estimate that reduced metabolic demand by passive energy recapture
      improves the cost of transport by 48%, allowing jellyfish to achieve the large
      sizes required for sufficient prey encounters. Pressure calculations, using both
      computational fluid dynamics and a newly developed method from empirical velocity
      field measurements, demonstrate that this extra thrust results from positive
      pressure created by a vortex ring underneath the bell during the refilling phase
      of swimming. These results demonstrate a physical basis for the ecological
      success of medusan swimmers despite their simple body plan. Results from this
      study also have implications for bioinspired design, where low-energy propulsion
      is required. 

PMID- 24101460
TI  - Regulation of p53 is critical for vertebrate limb regeneration.
AB  - Extensive regeneration of the vertebrate body plan is found in salamander and
      fish species. In these organisms, regeneration takes place through reprogramming
      of differentiated cells, proliferation, and subsequent redifferentiation of adult
      tissues. Such plasticity is rarely found in adult mammalian tissues, and this has
      been proposed as the basis of their inability to regenerate complex structures.
      Despite their importance, the mechanisms underlying the regulation of the
      differentiated state during regeneration remain unclear. Here, we analyzed the
      role of the tumor-suppressor p53 during salamander limb regeneration. The
      activity of p53 initially decreases and then returns to baseline. Its down
      regulation is required for formation of the blastema, and its up-regulation is
      necessary for the redifferentiation phase. Importantly, we show that a decrease
      in the level of p53 activity is critical for cell cycle reentry of postmitotic,
      differentiated cells, whereas an increase is required for muscle differentiation.
      In addition, we have uncovered a potential mechanism for the regulation of p53
      during limb regeneration, based on its competitive inhibition by DeltaNp73. Our
      results suggest that the regulation of p53 activity is a pivotal mechanism that
      controls the plasticity of the differentiated state during regeneration. 

PMID- 24101462
TI  - Impact of trehalose transporter knockdown on Anopheles gambiae stress adaptation
      and susceptibility to Plasmodium falciparum infection.
AB  - Anopheles gambiae is a major vector mosquito for Plasmodium falciparum, the
      deadly pathogen causing most human malaria in sub-Saharan Africa. Synthesized in
      the fat body, trehalose is the predominant sugar in mosquito hemolymph. It not
      only provides energy but also protects the mosquito against desiccation and heat
      stresses. Trehalose enters the mosquito hemolymph by the trehalose transporter
      AgTreT1. In adult female A. gambiae, AgTreT1 is predominantly expressed in the
      fat body. We found that AgTreT1 expression is induced by environmental stresses
      such as low humidity or elevated temperature. AgTreT1 RNA silencing reduces the
      hemolymph trehalose concentration by 40%, and the mosquitoes succumb sooner after
      exposure to desiccation or heat. After an infectious blood meal, AgTreT1 RNA
      silencing reduces the number of P. falciparum oocysts in the mosquito midgut by
      over 70% compared with mock-injected mosquitoes. These data reveal important
      roles for AgTreT1 in stress adaptation and malaria pathogen development in a
      major vector mosquito. Thus, AgTreT1 may be a potential target for malaria vector
      control. 

PMID- 24101464
TI  - Universal features in the photoemission spectroscopy of high-temperature
      superconductors.
AB  - The energy gap for electronic excitations is one of the most important
      characteristics of the superconducting state, as it directly reflects the pairing
      of electrons. In the copper-oxide high-temperature superconductors (HTSCs), a
      strongly anisotropic energy gap, which vanishes along high-symmetry directions,
      is a clear manifestation of the d-wave symmetry of the pairing. There is,
      however, a dramatic change in the form of the gap anisotropy with reduced carrier
      concentration (underdoping). Although the vanishing of the gap along the diagonal
      to the square Cu-O bond directions is robust, the doping dependence of the large
      gap along the Cu-O directions suggests that its origin might be different from
      pairing. It is thus tempting to associate the large gap with a second-order
      parameter distinct from superconductivity. We use angle-resolved photoemission
      spectroscopy to show that the two-gap behavior and the destruction of well
      defined electronic excitations are not universal features of HTSCs, and depend
      sensitively on how the underdoped materials are prepared. Depending on cation
      substitution, underdoped samples either show two-gap behavior or not. In
      contrast, many other characteristics of HTSCs, such as the dome-like dependence
      of on doping, long-lived excitations along the diagonals to the Cu-O bonds, and
      an energy gap at the Brillouin zone boundary that decreases monotonically with
      doping while persisting above (the pseudogap), are present in all samples,
      irrespective of whether they exhibit two-gap behavior or not. Our results imply
      that universal aspects of high- superconductivity are relatively insensitive to
      differences in the electronic states along the Cu-O bond directions. 

PMID- 24101463
TI  - Model-driven optimization of multicomponent self-assembly processes.
AB  - Here, we report an engineering approach toward multicomponent self-assembly
      processes by developing a methodology to circumvent spurious, metastable
      assemblies. The formation of metastable aggregates often hampers self-assembly of
      molecular building blocks into the desired nanostructures. Strategies are
      explored to master the pathway complexity and avoid off-pathway aggregates by
      optimizing the rate of assembly along the correct pathway. We study as a model
      system the coassembly of two monomers, the R- and S-chiral enantiomers of a pi
      conjugated oligo(p-phenylene vinylene) derivative. Coassembly kinetics are
      analyzed by developing a kinetic model, which reveals the initial assembly of
      metastable structures buffering free monomers and thereby slows the formation of
      thermodynamically stable assemblies. These metastable assemblies exert greater
      influence on the thermodynamically favored self-assembly pathway if the ratio
      between both monomers approaches 1:1, in agreement with experimental results.
      Moreover, competition by metastable assemblies is highly temperature dependent
      and hampers the assembly of equilibrium nanostructures most effectively at
      intermediate temperatures. We demonstrate that the rate of the assembly process
      may be optimized by tuning the cooling rate. Finally, it is shown by simulation
      that increasing the driving force for assembly stepwise by changing the solvent
      composition may circumvent metastable pathways and thereby force the assembly
      process directly into the correct pathway. 

PMID- 24101465
TI  - Arginine oscillation explains Na+ independence in the substrate/product
      antiporter CaiT.
AB  - Most secondary-active transporters transport their substrates using an
      electrochemical ion gradient. In contrast, the carnitine transporter (CaiT) is an
      ion-independent, l-carnitine/gamma-butyrobetaine antiporter belonging to the
      betaine/carnitine/choline transporter family of secondary transporters. Recently
      determined crystal structures of CaiT from Escherichia coli and Proteus mirabilis
      revealed an inverted five-transmembrane-helix repeat similar to that in the amino
      acid/Na(+) symporter LeuT. The ion independence of CaiT makes it unique in this
      family. Here we show that mutations of arginine 262 (R262) make CaiT Na(+)
      dependent. The transport activity of R262 mutants increased by 30-40% in the
      presence of a membrane potential, indicating substrate/Na(+) cotransport.
      Structural and biochemical characterization revealed that R262 plays a crucial
      role in substrate binding by stabilizing the partly unwound TM1' helix. Modeling
      CaiT from P. mirabilis in the outward-open and closed states on the corresponding
      structures of the related symporter BetP reveals alternating orientations of the
      buried R262 sidechain, which mimic sodium binding and unbinding in the Na(+)
      coupled substrate symporters. We propose that a similar mechanism is operative in
      other Na(+)/H(+)-independent transporters, in which a positively charged amino
      acid replaces the cotransported cation. The oscillation of the R262 sidechain in
      CaiT indicates how a positive charge triggers the change between outward-open and
      inward-open conformations as a unifying critical step in LeuT-type transporters. 

PMID- 24101466
TI  - High diversity of West African bat malaria parasites and a tight link with rodent
      Plasmodium taxa.
AB  - As the only volant mammals, bats are captivating for their high taxonomic
      diversity, for their vital roles in ecosystems--particularly as pollinators and
      insectivores--and, more recently, for their important roles in the maintenance
      and transmission of zoonotic viral diseases. Genome sequences have identified
      evidence for a striking expansion of and positive selection in gene families
      associated with immunity. Bats have also been known to be hosts of malaria
      parasites for over a century, and as hosts, they possess perhaps the most
      phylogenetically diverse set of hemosporidian genera and species. To provide a
      molecular framework for the study of these parasites, we surveyed bats in three
      remote areas of the Upper Guinean forest ecosystem. We detected four distinct
      genera of hemosporidian parasites: Plasmodium, Polychromophilus, Nycteria, and
      Hepatocystis. Intriguingly, the two species of Plasmodium in bats fall within the
      clade of rodent malaria parasites, indicative of multiple host switches across
      mammalian orders. We show that Nycteria species form a very distinct phylogenetic
      group and that Hepatocystis parasites display an unusually high diversity and
      prevalence in epauletted fruit bats. The diversity and high prevalence of novel
      lineages of chiropteran hemosporidians underscore the exceptional position of
      bats among all other mammalian hosts of hemosporidian parasites and support
      hypotheses of pathogen tolerance consistent with the exceptional immunology of
      bats.

PMID- 24101467
TI  - Menin promotes hepatocellular carcinogenesis and epigenetically up-regulates Yap1
      transcription.
AB  - Menin is a scaffold protein encoded by the multiple endocrine neoplasia type 1
      (MEN1) gene in humans, and it interacts with a variety of transcriptional
      proteins to control active or repressive cellular processes. Here, we show that
      heterozygous ablation of Men1 in female mice reduces chemical carcinogen-induced
      liver carcinogenesis and represses the activation of the inflammation pathway.
      Using ChIP-on-chip screens and ChIP assays, we find that menin occupancy
      frequently coincides with H3K4me3 at the promoter of many liver cancer-related
      genes, such as Yes-associated protein (Yap1). Increased menin and Yap1 expression
      in human hepatocellular carcinoma specimens was associated with poor prognosis.
      Our findings reveal that menin plays an important epigenetic role in promoting
      liver tumorigenesis, and support the notion that H3K4me3, which is regulated by
      the menin-mixed-lineage leukemia complex, is a potential therapeutic target in
      hepatocellular carcinoma. 

PMID- 24101468
TI  - Pressure-decoupled magnetic and structural transitions of the parent compound of
      iron-based 122 superconductors BaFe2As2.
AB  - The recent discovery of iron ferropnictide superconductors has received intensive
      concern in connection with magnetically involved superconductors. Prominent
      features of ferropnictide superconductors are becoming apparent: the parent
      compounds exhibit an antiferromagnetic ordered spin density wave (SDW) state, the
      magnetic-phase transition is always accompanied by a crystal structural
      transition, and superconductivity can be induced by suppressing the SDW phase via
      either chemical doping or applied external pressure to the parent state. These
      features generated considerable interest in the interplay between magnetism and
      structure in chemically doped samples, showing crystal structure transitions
      always precede or coincide with magnetic transition. Pressure-tuned transition,
      on the other hand, would be more straightforward to superconducting mechanism
      studies because there are no disorder effects caused by chemical doping; however,
      remarkably little is known about the interplay in the parent compounds under
      controlled pressure due to the experimental challenge of in situ measuring both
      of magnetic and crystal structure evolution at high pressure and low
      temperatures. Here we show from combined synchrotron Mossbauer and X-ray
      diffraction at high pressures that the magnetic ordering surprisingly precedes
      the structural transition at high pressures in the parent compound BaFe2As2, in
      sharp contrast to the chemical-doping case. The results can be well understood in
      terms of the spin fluctuations in the emerging nematic phase before the long
      range magnetic order that sheds light on understanding how the parent compound
      evolves from a SDW state to a superconducting phase, a key scientific inquiry of
      iron-based superconductors. 

PMID- 24101469
TI  - DNA supercoiling enhances cooperativity and efficiency of an epigenetic switch.
AB  - Bacteriophage lambda stably maintains its dormant prophage state but efficiently
      enters lytic development in response to DNA damage. The mediator of these
      processes is the lambda repressor protein, CI, and its interactions with lambda
      operator DNA. This lambda switch is a model on the basis of which epigenetic
      switch regulation is understood. Using single molecule analysis, we directly
      examined the stability of the CI-operator structure in its natural, supercoiled
      state. We marked positions adjacent to the lambda operators with peptide nucleic
      acids and monitored their movement by tethered particle tracking. Compared with
      relaxed DNA, the presence of supercoils greatly enhances juxtaposition
      probability. Also, the efficiency and cooperativity of the lambda switch is
      significantly increased in the supercoiled system compared with a linear assay,
      increasing the Hill coefficient. 

PMID- 24101470
TI  - HIF isoforms in the skin differentially regulate systemic arterial pressure.
AB  - Vascular flow through tissues is regulated via a number of homeostatic
      mechanisms. Localized control of tissue blood flow, or autoregulation, is a key
      factor in regulating tissue perfusion and oxygenation. We show here that the net
      balance between two hypoxia-inducible factor (HIF) transcription factor isoforms,
      HIF-1alpha and HIF-2alpha, is an essential mechanism regulating both local and
      systemic blood flow in the skin of mice. We also show that balance of HIF
      isoforms in keratinocyte-specific mutant mice affects thermal adaptation,
      exercise capacity, and systemic arterial pressure. The two primary HIF isoforms
      achieve these effects in opposing ways that are associated with HIF isoform
      regulation of nitric oxide production. We also show that a correlation exists
      between altered levels of HIF isoforms in the skin and the degree of idiopathic
      hypertension in human subjects. Thus, the balance between HIF-1alpha and HIF
      2alpha expression in keratinocytes is a control element of both tissue perfusion
      and systemic arterial pressure, with potential implications in human
      hypertension. 

PMID- 24101471
TI  - CDC5, a DNA binding protein, positively regulates posttranscriptional processing
      and/or transcription of primary microRNA transcripts.
AB  - CDC5 is a MYB-related protein that exists in plants, animals, and fungi. In
      Arabidopsis, CDC5 regulates both growth and immunity through unknown mechanisms.
      Here, we show that CDC5 from Arabidopsis positively regulates the accumulation of
      microRNAs (miRNAs), which control many biological processes including development
      and adaptations to environments in plants. CDC5 interacts with both the promoters
      of genes encoding miRNAs (MIR) and the DNA-dependent RNA polymerase II. As a
      consequence, lack of CDC5 reduces the occupancy of polymerase II at MIR
      promoters, as well as MIR promoter activities. In addition, CDC5 is associated
      with the DICER-LIKE1 complex, which generates miRNAs from their primary
      transcripts and is required for efficient miRNA production. These results suggest
      that CDC5 may have dual roles in miRNA biogenesis: functioning as a positive
      transcription factor of MIR and/or acting as a component of the DICER-LIKE1
      complex to enhance primary miRNA processing. 

PMID- 24101472
TI  - Astrocyte control of synaptic NMDA receptors contributes to the progressive
      development of temporal lobe epilepsy.
AB  - Astrocytes modulate neuronal activity, synaptic transmission, and behavior by
      releasing chemical transmitters in a process termed gliotransmission. Whether
      this process impacts epilepsy in vivo is not known. We show that genetic
      impairment of transmitter release from astrocytes by the expression of a glial
      dominant-negative SNARE domain in mice reduced epileptiform activity in situ,
      delayed seizure onset after pilocarpine-induced status epilepticus, and
      attenuated subsequent progressive increase in seizure frequency in vivo. The
      reduced seizure frequency was accompanied by attenuation of hippocampal damage
      and behavioral deficits. As the delay in seizure onset and the reduced seizure
      frequency were mimicked by intracerebroventricular delivery of the NMDA receptor
      (NMDAR) antagonist D-(-)-2-amino-5-phosphonopentanoate in WT littermates and
      because dominant-negative SNARE expression leads to a hypofunction of synaptic
      NMDARs, we conclude that astrocytes modulate epileptogenesis, recurrent
      spontaneous seizures, and pathophysiological consequences of epilepsy through a
      pathway involving NMDARs.

PMID- 24101473
TI  - Fast and accurate nonenzymatic copying of an RNA-like synthetic genetic polymer.
AB  - Recent advances suggest that it may be possible to construct simple artificial
      cells from two subsystems: a self-replicating cell membrane and a self
      replicating genetic polymer. Although multiple pathways for the growth and
      division of model protocell membranes have been characterized, no self
      replicating genetic material is yet available. Nonenzymatic template-directed
      synthesis of RNA with activated ribonucleotide monomers has led to the copying of
      short RNA templates; however, these reactions are generally slow (taking days to
      weeks) and highly error prone. N3'-P5'-linked phosphoramidate DNA (3'-NP-DNA) is
      similar to RNA in its overall duplex structure, and is attractive as an
      alternative to RNA because the high reactivity of its corresponding monomers
      allows rapid and efficient copying of all four nucleobases on homopolymeric RNA
      and DNA templates. Here we show that both homopolymeric and mixed-sequence 3'-NP
      DNA templates can be copied into complementary 3'-NP-DNA sequences. G:T and A:C
      wobble pairing leads to a high error rate, but the modified nucleoside 2
      thiothymidine suppresses wobble pairing. We show that the 2-thiothymidine
      modification increases both polymerization rate and fidelity in the copying of a
      3'-NP-DNA template into a complementary strand of 3'-NP-DNA. Our results suggest
      that 3'-NP-DNA has the potential to serve as the genetic material of artificial
      biological systems. 

PMID- 24101474
TI  - Structural basis for Spt5-mediated recruitment of the Paf1 complex to chromatin.
AB  - Polymerase associated factor 1 complex (Paf1C) broadly influences gene expression
      by regulating chromatin structure and the recruitment of RNA-processing factors
      during transcription elongation. The Plus3 domain of the Rtf1 subunit mediates
      Paf1C recruitment to genes by binding a repeating domain within the elongation
      factor Spt5 (suppressor of Ty). Here we provide a molecular description of this
      interaction by reporting the structure of human Rtf1 Plus3 in complex with a
      phosphorylated Spt5 repeat. We find that Spt5 binding is mediated by an extended
      surface containing phosphothreonine recognition and hydrophobic interfaces that
      interact with residues outside the Spt5 motif. Changes within these interfaces
      diminish binding of Spt5 in vitro and chromatin localization of Rtf1 in vivo. The
      structure reveals the basis for recognition of the repeat motif of Spt5, a key
      player in the recruitment of gene regulatory factors to RNA polymerase II. 

PMID- 24101475
TI  - Structures of the flax-rust effector AvrM reveal insights into the molecular
      basis of plant-cell entry and effector-triggered immunity.
AB  - Fungal and oomycete pathogens cause some of the most devastating diseases in crop
      plants, and facilitate infection by delivering a large number of effector
      molecules into the plant cell. AvrM is a secreted effector protein from flax rust
      (Melampsora lini) that can internalize into plant cells in the absence of the
      pathogen, binds to phosphoinositides (PIPs), and is recognized directly by the
      resistance protein M in flax (Linum usitatissimum), resulting in effector
      triggered immunity. We determined the crystal structures of two naturally
      occurring variants of AvrM, AvrM-A and avrM, and both reveal an L-shaped fold
      consisting of a tandem duplicated four-helix motif, which displays similarity to
      the WY domain core in oomycete effectors. In the crystals, both AvrM variants
      form a dimer with an unusual nonglobular shape. Our functional analysis of AvrM
      reveals that a hydrophobic surface patch conserved between both variants is
      required for internalization into plant cells, whereas the C-terminal coiled-coil
      domain mediates interaction with M. AvrM binding to PIPs is dependent on positive
      surface charges, and mutations that abrogate PIP binding have no significant
      effect on internalization, suggesting that AvrM binding to PIPs is not essential
      for transport of AvrM across the plant membrane. The structure of AvrM and the
      identification of functionally important surface regions advance our
      understanding of the molecular mechanisms underlying how effectors enter plant
      cells and how they are detected by the plant immune system. 

PMID- 24101476
TI  - Neofunctionalization of young duplicate genes in Drosophila.
AB  - Gene duplication is a key source of genetic innovation that plays a role in the
      evolution of phenotypic complexity. Although several evolutionary processes can
      result in the long-term retention of duplicate genes, their relative
      contributions in nature are unknown. Here we develop a phylogenetic approach for
      comparing genome-wide expression profiles of closely related species to quantify
      the roles of conservation, neofunctionalization, subfunctionalization, and
      specialization in the preservation of duplicate genes. Application of our method
      to pairs of young duplicates in Drosophila shows that neofunctionalization, the
      gain of a novel function in one copy, accounts for the retention of almost two
      thirds of duplicate genes. Surprisingly, novel functions nearly always originate
      in younger (child) copies, whereas older (parent) copies possess functions
      similar to those of ancestral genes. Further examination of such pairs reveals a
      strong bias toward RNA-mediated duplication events, implicating asymmetric
      duplication and positive selection in the evolution of new functions. Moreover,
      we show that young duplicate genes are expressed primarily in testes and that
      their expression breadth increases over evolutionary time. This finding supports
      the "out-of-testes" hypothesis, which posits that testes are a catalyst for the
      emergence of new genes that ultimately evolve functions in other tissues. Thus,
      our study highlights the importance of neofunctionalization and positive
      selection in the retention of young duplicates in Drosophila and illustrates how
      duplicates become incorporated into novel functional networks over evolutionary
      time. 

PMID- 24101477
TI  - Modulation of macrophage phenotype by cell shape.
AB  - Phenotypic polarization of macrophages is regulated by a milieu of cues in the
      local tissue microenvironment. Although much is known about how soluble factors
      influence macrophage polarization, relatively little is known about how physical
      cues present in the extracellular environment might modulate proinflammatory (M1)
      vs. prohealing (M2) activation. Specifically, the role of cell shape has not been
      explored, even though it has been observed that macrophages adopt different
      geometries in vivo. We and others observed that macrophages polarized toward
      different phenotypes in vitro exhibit dramatic changes in cell shape: M2 cells
      exhibit an elongated shape compared with M1 cells. Using a micropatterning
      approach to control macrophage cell shape directly, we demonstrate here that
      elongation itself, without exogenous cytokines, leads to the expression of M2
      phenotype markers and reduces the secretion of inflammatory cytokines. Moreover,
      elongation enhances the effects of M2-inducing cytokines IL-4 and IL-13 and
      protects cells from M1-inducing stimuli LPS and IFN-gamma. In addition shape- but
      not cytokine-induced polarization is abrogated when actin and actin/myosin
      contractility are inhibited by pharmacological agents, suggesting a role for the
      cytoskeleton in the control of macrophage polarization by cell geometry. Our
      studies demonstrate that alterations in cell shape associated with changes in ECM
      architecture may provide integral cues to modulate macrophage phenotype
      polarization. 

PMID- 24101478
TI  - Humanized mouse model of glucose 6-phosphate dehydrogenase deficiency for in vivo
      assessment of hemolytic toxicity.
AB  - Individuals with glucose 6-phosphate dehydrogenase (G6PD) deficiency are at risk
      for the development of hemolytic anemia when given 8-aminoquinolines (8-AQs), an
      important class of antimalarial/antiinfective therapeutics. However, there is no
      suitable animal model that can predict the clinical hemolytic potential of drugs.
      We developed and validated a human (hu)RBC-SCID mouse model by giving nonobese
      diabetic/SCID mice daily transfusions of huRBCs from G6PD-deficient donors.
      Treatment of SCID mice engrafted with G6PD-deficient huRBCs with primaquine, an 8
      AQ, resulted in a dose-dependent selective loss of huRBCs. To validate the
      specificity of this model, we tested known nonhemolytic antimalarial drugs:
      mefloquine, chloroquine, doxycycline, and pyrimethamine. No significant loss of
      G6PD-deficient huRBCs was observed. Treatment with drugs known to cause hemolytic
      toxicity (pamaquine, sitamaquine, tafenoquine, and dapsone) resulted in loss of
      G6PD-deficient huRBCs comparable to primaquine. This mouse model provides an
      important tool to test drugs for their potential to cause hemolytic toxicity in
      G6PD-deficient populations. 

PMID- 24101479
TI  - Changes in ecosystem resilience detected in automated measures of ecosystem
      metabolism during a whole-lake manipulation.
AB  - Environmental sensor networks are developing rapidly to assess changes in
      ecosystems and their services. Some ecosystem changes involve thresholds, and
      theory suggests that statistical indicators of changing resilience can be
      detected near thresholds. We examined the capacity of environmental sensors to
      assess resilience during an experimentally induced transition in a whole-lake
      manipulation. A trophic cascade was induced in a planktivore-dominated lake by
      slowly adding piscivorous bass, whereas a nearby bass-dominated lake remained
      unmanipulated and served as a reference ecosystem during the 4-y experiment. In
      both the manipulated and reference lakes, automated sensors were used to measure
      variables related to ecosystem metabolism (dissolved oxygen, pH, and chlorophyll
      a concentration) and to estimate gross primary production, respiration, and net
      ecosystem production. Thresholds were detected in some automated measurements
      more than a year before the completion of the transition to piscivore dominance.
      Directly measured variables (dissolved oxygen, pH, and chlorophyll-a
      concentration) related to ecosystem metabolism were better indicators of the
      approaching threshold than were the estimates of rates (gross primary production,
      respiration, and net ecosystem production); this difference was likely a result
      of the larger uncertainties in the derived rate estimates. Thus, relatively
      simple characteristics of ecosystems that were observed directly by the sensors
      were superior indicators of changing resilience. Models linked to thresholds in
      variables that are directly observed by sensor networks may provide unique
      opportunities for evaluating resilience in complex ecosystems. 

PMID- 24101481
TI  - Vegetation controls on the maximum size of coastal dunes.
AB  - Coastal dunes, in particular foredunes, support a resilient ecosystem and reduce
      coastal vulnerability to storms. In contrast to dry desert dunes, coastal dunes
      arise from interactions between biological and physical processes. Ecologists
      have traditionally addressed coastal ecosystems by assuming that they adapt to
      preexisting dune topography, whereas geomorphologists have studied the properties
      of foredunes primarily in connection to physical, not biological, factors. Here,
      we study foredune development using an ecomorphodynamic model that resolves the
      coevolution of topography and vegetation in response to both physical and
      ecological factors. We find that foredune growth is eventually limited by a
      negative feedback between wind flow and topography. As a consequence, steady
      state foredunes are scale invariant, which allows us to derive scaling relations
      for maximum foredune height and formation time. These relations suggest that
      plant zonation (in particular for strand "dune-building" species) is the primary
      factor controlling the maximum size of foredunes and therefore the amount of sand
      stored in a coastal dune system. We also find that aeolian sand supply to the
      dunes determines the timescale of foredune formation. These results offer a
      potential explanation for the empirical relation between beach type and foredune
      size, in which large (small) foredunes are found on dissipative (reflective)
      beaches. Higher waves associated with dissipative beaches increase the
      disturbance of strand species, which shifts foredune formation landward and thus
      leads to larger foredunes. In this scenario, plants play a much more active role
      in modifying their habitat and altering coastal vulnerability than previously
      thought. 

PMID- 24101480
TI  - TALEN-engineered AR gene rearrangements reveal endocrine uncoupling of androgen
      receptor in prostate cancer.
AB  - Androgen receptor (AR) target genes direct development and survival of the
      prostate epithelial lineage, including prostate cancer (PCa). Thus, endocrine
      therapies that inhibit the AR ligand-binding domain (LBD) are effective in
      treating PCa. AR transcriptional reactivation is central to resistance, as
      evidenced by the efficacy of AR retargeting in castration-resistant PCa (CRPC)
      with next-generation endocrine therapies abiraterone and enzalutamide. However,
      resistance to abiraterone and enzalutamide limits this efficacy in most men, and
      PCa remains the second-leading cause of male cancer deaths. Here we show that AR
      gene rearrangements in CRPC tissues underlie a completely androgen-independent,
      yet AR-dependent, resistance mechanism. We discovered intragenic AR gene
      rearrangements in CRPC tissues, which we modeled using transcription activator
      like effector nuclease (TALEN)-mediated genome engineering. This modeling
      revealed that these AR gene rearrangements blocked full-length AR synthesis, but
      promoted expression of truncated AR variant proteins lacking the AR ligand
      binding domain. Furthermore, these AR variant proteins maintained the
      constitutive activity of the AR transcriptional program and a CRPC growth
      phenotype independent of full-length AR or androgens. These findings demonstrate
      that AR gene rearrangements are a unique resistance mechanism by which AR
      transcriptional activity can be uncoupled from endocrine regulation in CRPC. 

PMID- 24101482
TI  - Excitable human dynamics driven by extrinsic events in massive communities.
AB  - Using empirical data from a social media site (Twitter) and on trading volumes of
      financial securities, we analyze the correlated human activity in massive social
      organizations. The activity, typically excited by real-world events and measured
      by the occurrence rate of international brand names and trading volumes, is
      characterized by intermittent fluctuations with bursts of high activity separated
      by quiescent periods. These fluctuations are broadly distributed with an inverse
      cubic tail and have long-range temporal correlations with a power spectrum. We
      describe the activity by a stochastic point process and derive the distribution
      of activity levels from the corresponding stochastic differential equation. The
      distribution and the corresponding power spectrum are fully consistent with the
      empirical observations. 

PMID- 24101483
TI  - Evidence for supernova injection into the solar nebula and the decoupling of r
      process nucleosynthesis.
AB  - The isotopic composition of our Solar System reflects the blending of materials
      derived from numerous past nucleosynthetic events, each characterized by a
      distinct isotopic signature. We show that the isotopic compositions of elements
      spanning a large mass range in the earliest formed solids in our Solar System,
      calcium-aluminum-rich inclusions (CAIs), are uniform, and yet distinct from the
      average Solar System composition. Relative to younger objects in the Solar
      System, CAIs contain positive r-process anomalies in isotopes A < 140 and
      negative r-process anomalies in isotopes A > 140. This fundamental difference in
      the isotopic character of CAIs around mass 140 necessitates (i) the existence of
      multiple sources for r-process nucleosynthesis and (ii) the injection of
      supernova material into a reservoir untapped by CAIs. A scenario of late
      supernova injection into the protoplanetary disk is consistent with formation of
      our Solar System in an active star-forming region of the galaxy. 

PMID- 24101484
TI  - TERT promoter mutations in bladder cancer affect patient survival and disease
      recurrence through modification by a common polymorphism.
AB  - The telomerase reverse transcriptase (TERT) promoter, an important element of
      telomerase expression, has emerged as a target of cancer-specific mutations.
      Originally described in melanoma, the mutations in TERT promoter have been shown
      to be common in certain other tumor types that include glioblastoma,
      hepatocellular carcinoma, and bladder cancer. To fully define the occurrence and
      effect of the TERT promoter mutations, we investigated tumors from a well
      characterized series of 327 patients with urothelial cell carcinoma of bladder.
      The somatic mutations, mainly at positions -124 and -146 bp from ATG start site
      that create binding motifs for E-twenty six/ternary complex factors (Ets/TCF),
      affected 65.4% of the tumors, with even distribution across different stages and
      grades. Our data showed that a common polymorphism rs2853669, within a
      preexisting Ets2 binding site in the TERT promoter, acts as a modifier of the
      effect of the mutations on survival and tumor recurrence. The patients with the
      mutations showed poor survival in the absence [hazard ratio (HR) 2.19, 95%
      confidence interval (CI) 1.02-4.70] but not in the presence (HR 0.42, 95% CI 0.18
      1.01) of the variant allele of the polymorphism. The mutations in the absence of
      the variant allele were highly associated with the disease recurrence in patients
      with Tis, Ta, and T1 tumors (HR 1.85, 95% CI 1.11-3.08). The TERT promoter
      mutations are the most common somatic lesions in bladder cancer with clinical
      implications. The association of the mutations with patient survival and disease
      recurrence, subject to modification by a common polymorphism, can be a unique
      putative marker with individualized prognostic potential. 

PMID- 24101485
TI  - Delayed detection of climate mitigation benefits due to climate inertia and
      variability.
AB  - Climate change mitigation acts by reducing greenhouse gas emissions, and thus
      curbing, or even reversing, the increase in their atmospheric concentration. This
      reduces the associated anthropogenic radiative forcing, and hence the size of the
      warming. Because of the inertia and internal variability affecting the climate
      system and the global carbon cycle, it is unlikely that a reduction in warming
      would be immediately discernible. Here we use 21st century simulations from the
      latest ensemble of Earth System Model experiments to investigate and quantify
      when mitigation becomes clearly discernible. We use one of the scenarios as a
      reference for a strong mitigation strategy, Representative Concentration Pathway
      (RCP) 2.6 and compare its outcome with either RCP4.5 or RCP8.5, both of which are
      less severe mitigation pathways. We analyze global mean atmospheric CO2, and
      changes in annually and seasonally averaged surface temperature at global and
      regional scales. For global mean surface temperature, the median detection time
      of mitigation is about 25-30 y after RCP2.6 emissions depart from the higher
      emission trajectories. This translates into detection of a mitigation signal by
      2035 or 2045, depending on whether the comparison is with RCP8.5 or RCP4.5,
      respectively. The detection of climate benefits of emission mitigation occurs
      later at regional scales, with a median detection time between 30 and 45 y after
      emission paths separate. Requiring a 95% confidence level induces a delay of
      several decades, bringing detection time toward the end of the 21st century. 

PMID- 24101486
TI  - Drosophila seminal protein ovulin mediates ovulation through female octopamine
      neuronal signaling.
AB  - Across animal taxa, seminal proteins are important regulators of female
      reproductive physiology and behavior. However, little is understood about the
      physiological or molecular mechanisms by which seminal proteins effect these
      changes. To investigate this topic, we studied the increase in Drosophila
      melanogaster ovulation behavior induced by mating. Ovulation requires octopamine
      (OA) signaling from the central nervous system to coordinate an egg's release
      from the ovary and its passage into the oviduct. The seminal protein ovulin
      increases ovulation rates after mating. We tested whether ovulin acts through OA
      to increase ovulation behavior. Increasing OA neuronal excitability compensated
      for a lack of ovulin received during mating. Moreover, we identified a mating
      dependent relaxation of oviduct musculature, for which ovulin is a necessary and
      sufficient male contribution. We report further that oviduct muscle relaxation
      can be induced by activating OA neurons, requires normal metabolic production of
      OA, and reflects ovulin's increasing of OA neuronal signaling. Finally, we showed
      that as a result of ovulin exposure, there is subsequent growth of OA synaptic
      sites at the oviduct, demonstrating that seminal proteins can contribute to
      synaptic plasticity. Together, these results demonstrate that ovulin increases
      ovulation through OA neuronal signaling and, by extension, that seminal proteins
      can alter reproductive physiology by modulating known female pathways regulating
      reproduction. 

PMID- 24101487
TI  - Optogenetic-mediated increases in in vivo spontaneous activity disrupt pool
      specific but not dorsal-ventral motoneuron pathfinding.
AB  - Rhythmic waves of spontaneous electrical activity are widespread in the
      developing nervous systems of birds and mammals, and although many aspects of
      neural development are activity-dependent, it has been unclear if rhythmic waves
      are required for in vivo motor circuit development, including the proper
      targeting of motoneurons to muscles. We show here that electroporated
      channelrhodopsin-2 can be activated in ovo with light flashes to drive waves at
      precise intervals of approximately twice the control frequency in intact chicken
      embryos. Optical monitoring of associated axial movements ensured that the
      altered frequency was maintained. In embryos thus stimulated, motor axons
      correctly executed the binary dorsal-ventral pathfinding decision but failed to
      make the subsequent pool-specific decision to target to appropriate muscles. This
      observation, together with the previous demonstration that slowing the frequency
      by half perturbed dorsal-ventral but not pool-specific pathfinding, shows that
      modest changes in frequency differentially disrupt these two major pathfinding
      decisions. Thus, many drugs known to alter early rhythmic activity have the
      potential to impair normal motor circuit development, and given the conservation
      between mouse and avian spinal cords, our observations are likely relevant to
      mammals, where such studies would be difficult to carry out. 

PMID- 24101488
TI  - Nonfunctional NaV1.1 familial hemiplegic migraine mutant transformed into gain of
      function by partial rescue of folding defects.
AB  - Familial hemiplegic migraine (FHM) is a rare subtype of migraine with aura.
      Mutations causing FHM type 3 have been identified in SCN1A, the gene encoding the
      Nav1.1 Na(+) channel, which is also a major target of epileptogenic mutations and
      is particularly important for the excitability of GABAergic neurons. However,
      functional studies of NaV1.1 FHM mutations have generated controversial results.
      In particular, it has been shown that the NaV1.1-L1649Q mutant is nonfunctional
      when expressed in a human cell line because of impaired plasma membrane
      expression, similarly to NaV1.1 mutants that cause severe epilepsy, but we have
      observed gain-of-function effects for other NaV1.1 FHM mutants. Here we show that
      NaV1.1-L1649Q is nonfunctional because of folding defects that are rescuable by
      incubation at lower temperatures or coexpression of interacting proteins, and
      that a partial rescue is sufficient for inducing an overall gain of function
      because of the modifications in gating properties. Strikingly, when expressed in
      neurons, the mutant was partially rescued and was a constitutive gain of
      function. A computational model showed that 35% rescue can be sufficient for
      inducing gain of function. Interestingly, previously described folding-defective
      epileptogenic NaV1.1 mutants show loss of function also when rescued. Our results
      are consistent with gain of function as the functional effect of NaV1.1 FHM
      mutations and hyperexcitability of GABAergic neurons as the pathomechanism of FHM
      type 3. 

PMID- 24101489
TI  - Holocene dynamics of the Florida Everglades with respect to climate, dustfall,
      and tropical storms.
AB  - Aeolian dust is rarely considered an important source for nutrients in large
      peatlands, which generally develop in moist regions far from the major centers of
      dust production. As a result, past studies assumed that the Everglades provides a
      classic example of an originally oligotrophic, P-limited wetland that was
      subsequently degraded by anthropogenic activities. However, a multiproxy
      sedimentary record indicates that changes in atmospheric circulation patterns
      produced an abrupt shift in the hydrology and dust deposition in the Everglades
      over the past 4,600 y. A wet climatic period with high loadings of aeolian dust
      prevailed before 2800 cal BP (calibrated years before present) when vegetation
      typical of a deep slough dominated the principal drainage outlet of the
      Everglades. This dust was apparently transported from distant source areas, such
      as the Sahara Desert, by tropical storms according to its elemental chemistry and
      mineralogy. A drier climatic regime with a steep decline in dustfall persisted
      after 2800 cal BP maintaining sawgrass vegetation at the coring site as tree
      islands developed nearby (and pine forests covered adjacent uplands). The marked
      decline in dustfall was related to corresponding declines in sedimentary
      phosphorus, organic nitrogen, and organic carbon, suggesting that a close
      relationship existed between dustfall, primary production, and possibly,
      vegetation patterning before the 20th century. The climatic change after 2800 cal
      BP was probably produced by a shift in the Bermuda High to the southeast,
      shunting tropical storms to the south of Florida into the Gulf of Mexico. 

PMID- 24101490
TI  - Implication of the anti-inflammatory bioactive lipid prostaglandin D2-glycerol
      ester in the control of macrophage activation and inflammation by ABHD6.
AB  - Proinflammatory macrophages are key mediators in several pathologies; thus,
      controlling their activation is necessary. The endocannabinoid system is
      implicated in various inflammatory processes. Here we show that in macrophages,
      the newly characterized enzyme alpha/beta-hydrolase domain 6 (ABHD6) controls 2
      arachidonoylglycerol (2-AG) levels and thus its pharmacological effects.
      Furthermore, we characterize a unique pathway mediating the effects of 2-AG
      through its oxygenation by cyclooxygenase-2 to give rise to the anti-inflammatory
      prostaglandin D2-glycerol ester (PGD2-G). Pharmacological blockade of
      cyclooxygenase-2 or of prostaglandin D synthase prevented the effects of
      increasing 2-AG levels by ABHD6 inhibition in vitro, as well as the 2-AG-induced
      increase in PGD2-G levels. Together, our data demonstrate the physiological
      relevance of the interaction between the endocannabinoid and prostanoid systems.
      Moreover, we show that ABHD6 inhibition in vivo allows for fine-tuning of 2-AG
      levels in mice, therefore reducing lipopolysaccharide-induced inflammation,
      without the characteristic central side effects of strong increases in 2-AG
      levels obtained following monoacylglycerol lipase inhibition. In addition,
      administration of PGD2-G reduces lipopolysaccharide-induced inflammation in mice,
      thus confirming the biological relevance of this 2-AG metabolite. This points to
      ABHD6 as an interesting therapeutic target that should be relevant in treating
      inflammation-related conditions, and proposes PGD2-G as a bioactive lipid with
      potential anti-inflammatory properties in vivo. 

PMID- 24101492
TI  - Predictive effects of teachers and schools on test scores, college attendance,
      and earnings.
AB  - I studied predictive effects of teachers and schools on test scores in fourth
      through eighth grade and outcomes later in life such as college attendance and
      earnings. For example, predict the fraction of a classroom attending college at
      age 20 given the test score for a different classroom in the same school with the
      same teacher and given the test score for a classroom in the same school with a
      different teacher. I would like to have predictive effects that condition on
      averages over many classrooms, with and without the same teacher. I set up a
      factor model that, under certain assumptions, makes this feasible. Administrative
      school district data in combination with tax data were used to calculate
      estimates and do inference. 

PMID- 24101491
TI  - Structural analysis for glycolipid recognition by the C-type lectins Mincle and
      MCL.
AB  - Mincle [macrophage inducible Ca(2+)-dependent (C-type) lectin; CLEC4E] and MCL
      (macrophage C-type lectin; CLEC4D) are receptors for the cord factor TDM
      (trehalose-6,6'-dimycolate), a unique glycolipid of mycobacterial cell-surface
      components, and activate immune cells to confer adjuvant activity. Although it is
      known that receptor-TDM interactions require both sugar and lipid moieties of
      TDM, the mechanisms of glycolipid recognition by Mincle and MCL remain unclear.
      We here report the crystal structures of Mincle, MCL, and the Mincle-citric acid
      complex. The structures revealed that these receptors are capable of interacting
      with sugar in a Ca(2+)-dependent manner, as observed in other C-type lectins.
      However, Mincle and MCL uniquely possess shallow hydrophobic regions found
      adjacent to their putative sugar binding sites, which reasonably locate for
      recognition of fatty acid moieties of glycolipids. Functional studies using
      mutant receptors as well as glycolipid ligands support this deduced binding mode.
      These results give insight into the molecular mechanism of glycolipid recognition
      through C-type lectin receptors, which may provide clues to rational design for
      effective adjuvants. 

PMID- 24101493
TI  - Intrinsic-mediated caspase activation is essential for cardiomyocyte hypertrophy.
AB  - Cardiomyocyte hypertrophy is the cellular response that mediates pathologic
      enlargement of the heart. This maladaptation is also characterized by cell
      behaviors that are typically associated with apoptosis, including cytoskeletal
      reorganization and disassembly, altered nuclear morphology, and enhanced protein
      synthesis/translation. Here, we investigated the requirement of apoptotic caspase
      pathways in mediating cardiomyocyte hypertrophy. Cardiomyocytes treated with
      hypertrophy agonists displayed rapid and transient activation of the intrinsic
      mediated cell death pathway, characterized by elevated levels of caspase 9,
      followed by caspase 3 protease activity. Disruption of the intrinsic cell death
      pathway at multiple junctures led to a significant inhibition of cardiomyocyte
      hypertrophy during agonist stimulation, with a corresponding reduction in the
      expression of known hypertrophic markers (atrial natriuretic peptide) and
      transcription factor activity [myocyte enhancer factor-2, nuclear factor kappa B
      (NF-kappaB)]. Similarly, in vivo attenuation of caspase activity via adenoviral
      expression of the biologic effector caspase inhibitor p35 blunted cardiomyocyte
      hypertrophy in response to agonist stimulation. Treatment of cardiomyocytes with
      procaspase 3 activating compound 1, a small-molecule activator of caspase 3,
      resulted in a robust induction of the hypertrophy response in the absence of any
      agonist stimulation. These results suggest that caspase-dependent signaling is
      necessary and sufficient to promote cardiomyocyte hypertrophy. These results also
      confirm that cell death signal pathways behave as active remodeling agents in
      cardiomyocytes, independent of inducing an apoptosis response. 

PMID- 24101494
TI  - Mining the O-mannose glycoproteome reveals cadherins as major O-mannosylated
      glycoproteins.
AB  - The metazoan O-mannose (O-Man) glycoproteome is largely unknown. It has been
      shown that up to 30% of brain O-glycans are of the O-Man type, but essentially
      only alpha-dystroglycan (alpha-DG) of the dystrophin-glycoprotein complex is well
      characterized as an O-Man glycoprotein. Defects in O-Man glycosylation underlie
      congenital muscular dystrophies and considerable efforts have been devoted to
      explore this O-glycoproteome without much success. Here, we used our SimpleCell
      strategy using nuclease-mediated gene editing of a human cell line (MDA-MB-231)
      to reduce the structural heterogeneity of O-Man glycans and to probe the O-Man
      glycoproteome. In this breast cancer cell line we found that O-Man glycosylation
      is primarily found on cadherins and plexins on beta-strands in extracellular
      cadherin and Ig-like, plexin and transcription factor domains. The positions and
      evolutionary conservation of O-Man glycans in cadherins suggest that they play
      important functional roles for this large group of cell adhesion glycoproteins,
      which can now be addressed. The developed O-Man SimpleCell strategy is applicable
      to most types of cell lines and enables proteome-wide discovery of O-Man protein
      glycosylation. 

PMID- 24101495
TI  - Network model of top-down influences on local gain and contextual interactions in
      visual cortex.
AB  - The visual system uses continuity as a cue for grouping oriented line segments
      that define object boundaries in complex visual scenes. Many studies support the
      idea that long-range intrinsic horizontal connections in early visual cortex
      contribute to this grouping. Top-down influences in primary visual cortex (V1)
      play an important role in the processes of contour integration and perceptual
      saliency, with contour-related responses being task dependent. This suggests an
      interaction between recurrent inputs to V1 and intrinsic connections within V1
      that enables V1 neurons to respond differently under different conditions. We
      created a network model that simulates parametrically the control of local gain
      by hypothetical top-down modification of local recurrence. These local gain
      changes, as a consequence of network dynamics in our model, enable modulation of
      contextual interactions in a task-dependent manner. Our model displays contour
      related facilitation of neuronal responses and differential foreground vs.
      background responses over the neuronal ensemble, accounting for the perceptual
      pop-out of salient contours. It quantitatively reproduces the results of single
      unit recording experiments in V1, highlighting salient contours and replicating
      the time course of contextual influences. We show by means of phase-plane
      analysis that the model operates stably even in the presence of large inputs. Our
      model shows how a simple form of top-down modulation of the effective
      connectivity of intrinsic cortical connections among biophysically realistic
      neurons can account for some of the response changes seen in perceptual learning
      and task switching. 

PMID- 24101496
TI  - Human cytomegalovirus tegument protein pp150 acts as a cyclin A2-CDK-dependent
      sensor of the host cell cycle and differentiation state.
AB  - Upon cell entry, herpesviruses deliver a multitude of premade virion proteins to
      their hosts. The interplay between these incoming proteins and cell-specific
      regulatory factors dictates the outcome of infections at the cellular level.
      Here, we report a unique type of virion-host cell interaction that is essential
      for the cell cycle and differentiation state-dependent onset of human
      cytomegalovirus (HCMV) lytic gene expression. The major tegument 150-kDa
      phosphoprotein (pp150) of HCMV binds to cyclin A2 via a functional RXL/Cy motif
      resulting in its cyclin A2-dependent phosphorylation. Alanine substitution of the
      RXL/Cy motif prevents this interaction and allows the virus to fully escape the
      cyclin-dependent kinase (CDK)-mediated block of immediate early (IE) gene
      expression in S/G2 phase that normally restricts the onset of the HCMV
      replication cycle to G0/G1. Furthermore, the cyclin A2-CDK-pp150 axis is also
      involved in the establishment of HCMV quiescence in NTera2 cells, showing the
      importance of this molecular switch for differentiation state-dependent
      regulation of IE gene expression. Consistent with the known nucleocapsid-binding
      function of pp150, its RXL/Cy-dependent phosphorylation affects gene expression
      of the parental virion only, suggesting a cis-acting, virus particle-associated
      mechanism of control. The pp150 homologs of other primate and mammalian CMVs lack
      an RXL/Cy motif and accordingly even the nearest relative of HCMV, chimpanzee
      CMV, starts its lytic cycle in a cell cycle-independent manner. Thus, HCMV has
      evolved a molecular sensor for cyclin A2-CDK activity to restrict its IE gene
      expression program as a unique level of self-limitation and adaptation to its
      human host. 

PMID- 24101497
TI  - Expanded therapeutic potential in activity space of next-generation 5
      nitroimidazole antimicrobials with broad structural diversity.
AB  - Metronidazole and other 5-nitroimidazoles (5-NI) are among the most effective
      antimicrobials available against many important anaerobic pathogens, but evolving
      resistance is threatening their long-term clinical utility. The common 5-NIs were
      developed decades ago, yet little 5-NI drug development has since taken place,
      leaving the true potential of this important drug class unexplored. Here we
      report on a unique approach to the modular synthesis of diversified 5-NIs for
      broad exploration of their antimicrobial potential. Many of the more than 650
      synthesized compounds, carrying structurally diverse functional groups, have
      vastly improved activity against a range of microbes, including the pathogenic
      protozoa Giardia lamblia and Trichomonas vaginalis, and the bacterial pathogens
      Helicobacter pylori, Clostridium difficile, and Bacteroides fragilis.
      Furthermore, they can overcome different forms of drug resistance, and are active
      and nontoxic in animal infection models. These findings provide impetus to the
      development of structurally diverse, next-generation 5-NI drugs as agents in the
      antimicrobial armamentarium, thus ensuring their future viability as primary
      therapeutic agents against many clinically important infections. 

PMID- 24101498
TI  - Direct observation of structurally encoded metal discrimination and ether bond
      formation in a heterodinuclear metalloprotein.
AB  - Although metallocofactors are ubiquitous in enzyme catalysis, how metal binding
      specificity arises remains poorly understood, especially in the case of metals
      with similar primary ligand preferences such as manganese and iron. The
      biochemical selection of manganese over iron presents a particularly intricate
      problem because manganese is generally present in cells at a lower concentration
      than iron, while also having a lower predicted complex stability according to the
      Irving-Williams series (Mn(II) < Fe(II) < Ni(II) < Co(II) < Cu(II) > Zn(II)).
      Here we show that a heterodinuclear Mn/Fe cofactor with the same primary protein
      ligands in both metal sites self-assembles from Mn(II) and Fe(II) in vitro, thus
      diverging from the Irving-Williams series without requiring auxiliary factors
      such as metallochaperones. Crystallographic, spectroscopic, and computational
      data demonstrate that one of the two metal sites preferentially binds Fe(II) over
      Mn(II) as expected, whereas the other site is nonspecific, binding equal amounts
      of both metals in the absence of oxygen. Oxygen exposure results in further
      accumulation of the Mn/Fe cofactor, indicating that cofactor assembly is at least
      a two-step process governed by both the intrinsic metal specificity of the
      protein scaffold and additional effects exerted during oxygen binding or
      activation. We further show that the mixed-metal cofactor catalyzes a two
      electron oxidation of the protein scaffold, yielding a tyrosine-valine ether
      cross-link. Theoretical modeling of the reaction by density functional theory
      suggests a multistep mechanism including a valyl radical intermediate. 

PMID- 24101499
TI  - Design principles governing the motility of myosin V.
AB  - The molecular motor myosin V (MyoV) exhibits a wide repertoire of pathways during
      the stepping process, which is intimately connected to its biological function.
      The best understood of these is the hand-over-hand stepping by a swinging lever
      arm movement toward the plus end of actin filaments. Single-molecule experiments
      have also shown that the motor "foot stomps," with one hand detaching and
      rebinding to the same site, and back-steps under sufficient load. The complete
      taxonomy of MyoV's load-dependent stepping pathways, and the extent to which
      these are constrained by motor structure and mechanochemistry, are not
      understood. Using a polymer model, we develop an analytical theory to describe
      the minimal physical properties that govern motor dynamics. We solve the first
      passage problem of the head reaching the target-binding site, investigating the
      competing effects of backward load, strain in the leading head biasing the
      diffusion in the direction of the target, and the possibility of preferential
      binding to the forward site due to the recovery stroke. The theory reproduces a
      variety of experimental data, including the power stroke and slow diffusive
      search regimes in the mean trajectory of the detached head, and the force
      dependence of the forward-to-backward step ratio, run length, and velocity. We
      derive a stall force formula, determined by lever arm compliance and chemical
      cycle rates. By exploring the MyoV design space, we predict that it is a robust
      motor whose dynamical behavior is not compromised by reasonable perturbations to
      the reaction cycle and changes in the architecture of the lever arm. 

PMID- 24101500
TI  - Minimal mechanistic model of siRNA-dependent target RNA slicing by recombinant
      human Argonaute 2 protein.
AB  - Argonaute (Ago) proteins are the key component of the RNA-induced silencing
      complex and mediate RNA interference (RNAi) in association with small RNAs.
      Although overall the mechanism of RNAi is well understood, many molecular details
      of this complex process are not. Here we report about in-depth steady-state and,
      in particular, pre-steady-state characterization of siRNA binding, target RNA
      recognition, sequence-specific cleavage and product release by recombinant human
      Ago 2 (hAgo2). In combining our biochemical studies with crystal structures of
      bacterial Ago proteins and of recently released hAgo2, we relate kinetic data to
      conformational changes along the pathway and propose a comprehensive minimal
      mechanistic model describing fundamental steps during RNAi. Furthermore, in
      contrast to the current conception, our hAgo2 preparations are programmable with
      double-stranded siRNA. Accordingly, the system investigated represents a
      functional minimal RNA-induced silencing complex. 

PMID- 24101501
TI  - Milk oligosaccharide sialyl(alpha2,3)lactose activates intestinal CD11c+ cells
      through TLR4.
AB  - Breast milk oligosaccharides shape the intestinal environment by affecting
      mucosal immunity and bacterial colonization. To clarify the role of milk
      oligosaccharide sialyl(alpha2,3)lactose (3SL) in intestinal physiology and
      disease, we investigated colitis development in Il10(-/-) mice exposed to normal
      or 3SL-deficient milk during lactation. Onset and progression of intestinal
      inflammation were delayed in Il10(-/-) mice deficient for the alpha2,3
      sialyltransferase 4 (ST3GAL4) responsible for 3SL biosynthesis. The
      proinflammatory role of 3SL was confirmed by showing that oral supplementation of
      newborn Il10(-/-);St3gal4(-/-) mice with 3SL increased colitis severity.
      Conversely, fostering of newborn Il10(-/-) mice to lactating St3gal4(-/-) mothers
      reduced colitis severity. 3SL directly stimulated mesenteric lymph node CD11c(+)
      dendritic cells and induced production of cytokines required for expansion of TH1
      and TH17 T cells. The stimulatory effect of 3SL was attenuated in Tlr4-deficient
      CD11c(+) cells, demonstrating that 3SL induces inflammation through Toll-like
      receptor 4 (TLR4) signaling. Thus, 3SL directly modulates mucosal immunity, which
      increases susceptibility to colitis. 

PMID- 24101502
TI  - Molecular understanding of atmospheric particle formation from sulfuric acid and
      large oxidized organic molecules.
AB  - Atmospheric aerosols formed by nucleation of vapors affect radiative forcing and
      therefore climate. However, the underlying mechanisms of nucleation remain
      unclear, particularly the involvement of organic compounds. Here, we present high
      resolution mass spectra of ion clusters observed during new particle formation
      experiments performed at the Cosmics Leaving Outdoor Droplets chamber at the
      European Organization for Nuclear Research. The experiments involved sulfuric
      acid vapor and different stabilizing species, including ammonia and
      dimethylamine, as well as oxidation products of pinanediol, a surrogate for
      organic vapors formed from monoterpenes. A striking resemblance is revealed
      between the mass spectra from the chamber experiments with oxidized organics and
      ambient data obtained during new particle formation events at the Hyytiala boreal
      forest research station. We observe that large oxidized organic compounds,
      arising from the oxidation of monoterpenes, cluster directly with single sulfuric
      acid molecules and then form growing clusters of one to three sulfuric acid
      molecules plus one to four oxidized organics. Most of these organic compounds
      retain 10 carbon atoms, and some of them are remarkably highly oxidized (oxygen
      to-carbon ratios up to 1.2). The average degree of oxygenation of the organic
      compounds decreases while the clusters are growing. Our measurements therefore
      connect oxidized organics directly, and in detail, with the very first steps of
      new particle formation and their growth between 1 and 2 nm in a controlled
      environment. Thus, they confirm that oxidized organics are involved in both the
      formation and growth of particles under ambient conditions. 

PMID- 24101503
TI  - 3D printing of microscopic bacterial communities.
AB  - Bacteria communicate via short-range physical and chemical signals, interactions
      known to mediate quorum sensing, sporulation, and other adaptive phenotypes.
      Although most in vitro studies examine bacterial properties averaged over large
      populations, the levels of key molecular determinants of bacterial fitness and
      pathogenicity (e.g., oxygen, quorum-sensing signals) may vary over micrometer
      scales within small, dense cellular aggregates believed to play key roles in
      disease transmission. A detailed understanding of how cell-cell interactions
      contribute to pathogenicity in natural, complex environments will require a new
      level of control in constructing more relevant cellular models for assessing
      bacterial phenotypes. Here, we describe a microscopic three-dimensional (3D)
      printing strategy that enables multiple populations of bacteria to be organized
      within essentially any 3D geometry, including adjacent, nested, and free-floating
      colonies. In this laser-based lithographic technique, microscopic containers are
      formed around selected bacteria suspended in gelatin via focal cross-linking of
      polypeptide molecules. After excess reagent is removed, trapped bacteria are
      localized within sealed cavities formed by the cross-linked gelatin, a highly
      porous material that supports rapid growth of fully enclosed cellular populations
      and readily transmits numerous biologically active species, including
      polypeptides, antibiotics, and quorum-sensing signals. Using this approach, we
      show that a picoliter-volume aggregate of Staphylococcus aureus can display
      substantial resistance to beta-lactam antibiotics by enclosure within a shell
      composed of Pseudomonas aeruginosa. 

PMID- 24101504
TI  - Tooth wear and dentoalveolar remodeling are key factors of morphological
      variation in the Dmanisi mandibles.
AB  - The Plio-Pleistocene hominin sample from Dmanisi (Georgia), dated to 1.77 million
      years ago, is unique in offering detailed insights into patterns of morphological
      variation within a paleodeme of early Homo. Cranial and dentoalveolar
      morphologies exhibit a high degree of diversity, but the causes of variation are
      still relatively unexplored. Here we show that wear-related dentoalveolar
      remodeling is one of the principal mechanisms causing mandibular shape variation
      in fossil Homo and in modern human hunter-gatherer populations. We identify a
      consistent pattern of mandibular morphological alteration, suggesting that dental
      wear and compensatory remodeling mechanisms remained fairly constant throughout
      the evolution of the genus Homo. With increasing occlusal and interproximal tooth
      wear, the teeth continue to erupt, the posterior dentition tends to drift in a
      mesial direction, and the front teeth become more upright. The resulting changes
      in dentognathic size and shape are substantial and need to be taken into account
      in comparative taxonomic analyses of isolated hominin mandibles. Our data further
      show that excessive tooth wear eventually leads to a breakdown of the normal
      remodeling mechanisms, resulting in dentognathic pathologies, tooth loss, and
      loss of masticatory function. Complete breakdown of dentognathic homeostasis,
      however, is unlikely to have limited the life span of early Homo because this
      effect was likely mediated by the preparation of soft foods. 

PMID- 24101505
TI  - Arabidopsis CRY2 and ZTL mediate blue-light regulation of the transcription
      factor CIB1 by distinct mechanisms.
AB  - Plants possess multiple photoreceptors to mediate light regulation of growth and
      development, but it is not well understood how different photoreceptors
      coordinate their actions to jointly regulate developmental responses, such as
      flowering time. In Arabidopsis, the photoexcited cryptochrome 2 interacts with
      the transcription factor CRYPTOCHROME-INTERACTING basic helix-loop-helix 1 (CIB1)
      to activate transcription and floral initiation. We show that the CIB1 protein
      expression is regulated by blue light; CIB1 is highly expressed in plants exposed
      to blue light, but levels of the CIB1 protein decreases in the absence of blue
      light. We demonstrate that CIB1 is degraded by the 26S proteasome and that blue
      light suppresses CIB1 degradation. Surprisingly, although cryptochrome 2
      physically interacts with CIB1 in response to blue light, it is not the
      photoreceptor mediating blue-light suppression of CIB1 degradation. Instead, two
      of the three light-oxygen-voltage (LOV)-domain photoreceptors, ZEITLUPE and LOV
      KELCH PROTEIN 2, but not FLAVIN-BINDING KELCH REPEAT 1, are required for the
      function and blue-light suppression of degradation of CIB1. These results support
      the hypothesis that the evolutionarily unrelated blue-light receptors,
      cryptochrome and LOV-domain F-box proteins, mediate blue-light regulation of the
      same transcription factor by distinct mechanisms. 

PMID- 24101506
TI  - Unique caudal plumage of Jeholornis and complex tail evolution in early birds.
AB  - The Early Cretaceous bird Jeholornis was previously only known to have a distally
      restricted ornamental frond of tail feathers. We describe a previously
      unrecognized fan-shaped tract of feathers situated dorsal to the proximal caudal
      vertebrae. The position and morphology of these feathers is reminiscent of the
      specialized upper tail coverts observed in males of some sexually dimorphic
      neornithines. As in the neornithine tail, the unique "two-tail" plumage in
      Jeholornis probably evolved as the result of complex interactions between natural
      and sexual selective pressures and served both aerodynamic and ornamental
      functions. We suggest that the proximal fan would have helped to streamline the
      body and reduce drag whereas the distal frond was primarily ornamental.
      Jeholornis reveals that tail evolution was complex and not a simple progression
      from frond to fan. 

PMID- 24101507
TI  - Illusory spirals and loops in crystal growth.
AB  - The theory of dislocation-controlled crystal growth identifies a continuous
      spiral step with an emergent lattice displacement on a crystal surface; a
      mechanistic corollary is that closely spaced, oppositely winding spirals merge to
      form concentric loops. In situ atomic force microscopy of step propagation on
      pathological L-cystine crystals did indeed show spirals and islands with step
      heights of one lattice displacement. We show by analysis of the rates of growth
      of smaller steps only one molecule high that the major morphological spirals and
      loops are actually consequences of the bunching of the smaller steps. The
      morphology of the bunched steps actually inverts the predictions of the theory:
      Spirals arise from pairs of dislocations, loops from single dislocations. Only
      through numerical simulation of the growth is it revealed how normal growth of
      anisotropic layers of molecules within the highly symmetrical crystals can
      conspire to create features in apparent violation of the classic theory.

PMID- 24101508
TI  - Oral delivery system prolongs blood circulation of docetaxel nanocapsules via
      lymphatic absorption.
AB  - An original oral formulation of docetaxel nanocapsules (NCs) embedded in
      microparticles elicited in rats a higher bioavailability compared with the i.v.
      administration of the commercial docetaxel solution, Taxotere. In the present
      study, various animal studies were designed to elucidate the absorption process
      of docetaxel from such a delivery system. Again, the docetaxel NC formulation
      elicited a marked enhanced absorption compared with oral Taxotere in minipigs,
      resulting in relative bioavailability and Cmax values 10- and 8.4-fold higher,
      respectively, confirming the previous rat study results. It was revealed that
      orally absorbed NCs altered the elimination and distribution of docetaxel, as
      shown in the organ biodistribution rat study, due to their reinforced coating,
      while transiting through the enterocytes by surface adsorption of apoproteins and
      phospholipids. These findings were demonstrated by the cryogenic-temperature
      transmission electron microscopy results and confirmed by the use of a
      chylomicron flow blocker, cycloheximide, that prevented the oral absorption of
      docetaxel from the NC formulation in an independent pharmacokinetic study. The
      lipoproteinated NCs reduced the docetaxel release in plasma and its distribution
      among the organs. The improved anticancer activity compared with i.v. Taxotere,
      observed in the metastatic lung cancer model in Severe Combined Immune Deficiency
      beige (SCID-bg) mice, should be attributed to the extravasation effect, leading
      to the lipoproteinated NC accumulation in lung tumors, where they exert a
      significant therapeutic action. To the best of our knowledge, no study has
      reported that the absorption of NCs was mediated by a lymphatic process and
      reinforced during their transit. 

PMID- 24101509
TI  - Regulation of estrogen receptor alpha by histone methyltransferase SMYD2-mediated
      protein methylation.
AB  - Estrogen receptor alpha (ERalpha) is a ligand-activated transcription factor.
      Upon estrogen stimulation, ERalpha recruits a number of coregulators, including
      both coactivators and corepressors, to the estrogen response elements, modulating
      gene activation or repression. Most coregulator complexes contain histone
      modifying enzymes to control ERalpha target gene expression in an epigenetic
      manner. In addition to histones, these epigenetic modifiers can modify nonhistone
      proteins including ERalpha, thereby constituting another layer of transcriptional
      regulation. Here we show that SET and MYND domain containing 2 (SMYD2), a histone
      H3K4 and H3K36 methyltransferase, directly methylates ERalpha protein at lysine
      266 (K266) both in vitro and in cells. In breast cancer MCF7 cells, SMYD2
      attenuates the chromatin recruitment of ERalpha to prevent ERalpha target gene
      activation under an estrogen-depleted condition. Importantly, the SMYD2-mediated
      repression of ERalpha target gene expression is mediated by the methylation of
      ERalpha at K266 in the nucleus, but not the methylation of histone H3K4. Upon
      estrogen stimulation, ERalpha-K266 methylation is diminished, thereby enabling
      p300/cAMP response element-binding protein-binding protein to acetylate ERalpha
      at K266, which is known to promote ERalpha transactivation activity. Our study
      identifies a previously undescribed inhibitory methylation event on ERalpha. Our
      data suggest that the dynamic cross-talk between SMYD2-mediated ERalpha protein
      methylation and p300/cAMP response element-binding protein-binding protein
      dependent ERalpha acetylation plays an important role in fine-tuning the
      functions of ERalpha at chromatin and the estrogen-induced gene expression
      profiles. 

PMID- 24101510
TI  - betaIV-Spectrin and CaMKII facilitate Kir6.2 regulation in pancreatic beta cells.
AB  - Identified over a dozen years ago in the brain and pancreatic islet, betaIV
      spectrin is critical for the local organization of protein complexes throughout
      the nervous system. betaIV-Spectrin targets ion channels and adapter proteins to
      axon initial segments and nodes of Ranvier in neurons, and betaIV-spectrin
      dysfunction underlies ataxia and early death in mice. Despite advances in betaIV
      spectrin research in the nervous system, its role in pancreatic islet biology is
      unknown. Here, we report that betaIV-spectrin serves as a multifunctional
      structural and signaling platform in the pancreatic islet. We report that betaIV
      spectrin directly associates with and targets the calcium/calmodulin-dependent
      protein kinase II (CaMKII) in pancreatic islets. In parallel, betaIV-spectrin
      targets ankyrin-B and the ATP-sensitive potassium channel. Consistent with these
      findings, betaIV-spectrin mutant mice lacking CaMKII- or ankyrin-binding motifs
      display selective loss of expression and targeting of key protein components,
      including CaMKIIdelta. betaIV-Spectrin-targeted CaMKII directly phosphorylates
      the inwardly-rectifying potassium channel, Kir6.2 (alpha subunit of KATP channel
      complex), and we identify the specific residue, Kir6.2 T224, responsible for
      CaMKII-dependent regulation of KATP channel function. CaMKII-dependent
      phosphorylation alters channel regulation resulting in KATP channel inhibition, a
      cellular phenotype consistent with aberrant insulin regulation. Finally, we
      demonstrate aberrant KATP channel phosphorylation in betaIV-spectrin mutant mice.
      In summary, our findings establish a broader role for betaIV-spectrin in
      regulation of cell membrane excitability in the pancreatic islet, define the
      pathway for CaMKII local control in pancreatic beta cells, and identify the
      mechanism for CaMKII-dependent regulation of KATP channels. 

PMID- 24101511
TI  - miRNA and mRNA cancer signatures determined by analysis of expression levels in
      large cohorts of patients.
AB  - Toward identifying a cancer-specific gene signature we applied surprisal analysis
      to the RNAs expression behavior for a large cohort of breast, lung, ovarian, and
      prostate carcinoma patients. We characterize the cancer phenotypic state as a
      shared response of a set of mRNA or microRNAs (miRNAs) in cancer patients versus
      noncancer controls. The resulting signature is robust with respect to individual
      patient variability and distinguishes with high fidelity between cancer and
      noncancer patients. The mRNAs and miRNAs that are implicated in the signature are
      correlated and are known to contribute to the regulation of cancer-signaling
      pathways. The miRNA and mRNA networks are common to the noncancer and cancer
      patients, but the disease modulates the strength of the connectivities.
      Furthermore, we experimentally assessed the cancer-specific signatures as
      possible therapeutic targets. Specifically we restructured a single dominant
      connectivity in the cancer-specific gene network in vitro. We find a deflection
      from the cancer phenotype, significantly reducing cancer cell proliferation and
      altering cancer cellular physiology. Our approach is grounded in thermodynamics
      augmented by information theory. The thermodynamic reasoning is demonstrated to
      ensure that the derived signature is bias-free and shows that the most
      significant redistribution of free energy occurs in programming a system between
      the noncancer and cancer states. This paper introduces a platform that can
      elucidate miRNA and mRNA behavior on a systems level and provides a comprehensive
      systematic view of both the energetics of the expression levels of RNAs and of
      their changes during tumorigenicity. 

PMID- 24101512
TI  - Greatwall is essential to prevent mitotic collapse after nuclear envelope
      breakdown in mammals.
AB  - Greatwall is a protein kinase involved in the inhibition of protein phosphatase 2
      (PP2A)-B55 complexes to maintain the mitotic state. Although its biochemical
      activity has been deeply characterized in Xenopus, its specific relevance during
      the progression of mitosis is not fully understood. By using a conditional
      knockout of the mouse ortholog, Mastl, we show here that mammalian Greatwall is
      essential for mouse embryonic development and cell cycle progression. Yet,
      Greatwall-null cells enter into mitosis with normal kinetics. However, these
      cells display mitotic collapse after nuclear envelope breakdown (NEB)
      characterized by defective chromosome condensation and prometaphase arrest.
      Intriguingly, Greatwall is exported from the nucleus to the cytoplasm in a CRM1
      dependent manner before NEB. This export occurs after the nuclear import of
      cyclin B-Cdk1 complexes, requires the kinase activity of Greatwall, and is
      mediated by Cdk-, but not Polo-like kinase 1-dependent phosphorylation. The
      mitotic collapse observed in Greatwall-deficient cells is partially rescued after
      concomitant depletion of B55 regulatory subunits, which are mostly cytoplasmic
      before NEB. These data suggest that Greatwall is an essential protein in mammals
      required to prevent mitotic collapse after NEB. 

PMID- 24101513
TI  - Serum deprivation inhibits the transcriptional co-activator YAP and cell growth
      via phosphorylation of the 130-kDa isoform of Angiomotin by the LATS1/2 protein
      kinases.
AB  - Large tumor suppressor (LATS)1/2 protein kinases transmit Hippo signaling in
      response to intercellular contacts and serum levels to limit cell growth via the
      inhibition of Yes-associated protein (YAP). Here low serum and high LATS1
      activity are found to enhance the levels of the 130-kDa isoform of angiomotin
      (Amot130) through phosphorylation by LATS1/2 at serine 175, which then forms a
      binding site for 14-3-3. Such phosphorylation, in turn, enables the ubiquitin
      ligase atrophin-1 interacting protein (AIP)4 to bind, ubiquitinate, and stabilize
      Amot130. Consistently, the Amot130 (S175A) mutant, which lacks LATS
      phosphorylation, bound AIP4 poorly under all conditions and showed reduced
      stability. Amot130 and AIP4 also promoted the ubiquitination and degradation of
      YAP in response to serum starvation, unlike Amot130 (S175A). Moreover, silencing
      Amot130 expression blocked LATS1 from inhibiting the expression of connective
      tissue growth factor, a YAP-regulated gene. Concordant with phosphorylated
      Amot130 specifically mediating these effects, wild-type Amot130 selectively
      induced YAP phosphorylation and reduced transcription of connective tissue growth
      factor in an AIP4-dependent manner versus Amot130 (S175A). Further, Amot130 but
      not Amot130 (S175A) strongly inhibited the growth of MDA-MB-468 breast cancer
      cells. The dominant-negative effects of Amot130 (S175A) on YAP signaling also
      support that phosphorylated Amot130 transduces Hippo signaling. Likewise, Amot130
      expression provoked premature growth arrest during mammary cell acini formation,
      whereas Amot130 (S175A)-expressing cells formed enlarged and poorly
      differentiated acini. Taken together, the phosphorylation of Amot130 by LATS is
      found to be a key feature that enables it to inhibit YAP-dependent signaling and
      cell growth. 

PMID- 24101514
TI  - DNA conformations in mismatch repair probed in solution by X-ray scattering from
      gold nanocrystals.
AB  - DNA metabolism and processing frequently require transient or metastable DNA
      conformations that are biologically important but challenging to characterize. We
      use gold nanocrystal labels combined with small angle X-ray scattering to
      develop, test, and apply a method to follow DNA conformations acting in the
      Escherichia coli mismatch repair (MMR) system in solution. We developed a neutral
      PEG linker that allowed gold-labeled DNAs to be flash-cooled and stored without
      degradation in sample quality. The 1,000-fold increased gold nanocrystal
      scattering vs. DNA enabled investigations at much lower concentrations than
      otherwise possible to avoid concentration-dependent tetramerization of the MMR
      initiation enzyme MutS. We analyzed the correlation scattering functions for the
      nanocrystals to provide higher resolution interparticle distributions not
      convoluted by the intraparticle distribution. We determined that mispair
      containing DNAs were bent more by MutS than complementary sequence DNA (csDNA),
      did not promote tetramer formation, and allowed MutS conversion to a sliding
      clamp conformation that eliminated the DNA bends. Addition of second protein
      responder MutL did not stabilize the MutS-bent forms of DNA. Thus, DNA distortion
      is only involved at the earliest mispair recognition steps of MMR: MutL does not
      trap bent DNA conformations, suggesting migrating MutL or MutS/MutL complexes as
      a conserved feature of MMR. The results promote a mechanism of mismatch DNA
      bending followed by straightening in initial MutS and MutL responses in MMR. We
      demonstrate that small angle X-ray scattering with gold labels is an enabling
      method to examine protein-induced DNA distortions key to the DNA repair,
      replication, transcription, and packaging. 

PMID- 24101515
TI  - Disruption of the expression of the proprotein convertase PC7 reduces BDNF
      production and affects learning and memory in mice.
AB  - PC7 belongs to the proprotein convertase family, whose members are implicated in
      the cleavage of secretory precursors. The in vivo function of PC7 is unknown.
      Herein, we find that the precursor proBDNF is processed into mature BDNF in COS-1
      cells coexpressing proBDNF with either PC7 or Furin. Conversely, the processing
      of proBDNF into BDNF is markedly reduced in the absence of either Furin or PC7 in
      mouse primary hepatocytes. In vivo we observe that BDNF and PC7 mRNAs are
      colocalized in mouse hippocampus and amygdala and that mature BDNF protein levels
      are reduced in these brain areas in PC7 KO mice but not in the hippocampus of
      PC1/3 KO mice. Various behavioral tests reveal that in PC7 KO mice spatial memory
      is intact and plasticity of responding is mildly abnormal. Episodic and emotional
      memories are severely impaired, but both are rescued with the tyrosine receptor
      kinase B agonist 7,8-dihydroxyflavone. Altogether, these results support an in
      vivo role for PC7 in the regulation of certain types of cognitive performance, in
      part via proBDNF processing. Because polymorphic variants of human PC7 are being
      characterized, it will be important in future studies to determine their effects
      on additional physiological and behavioral processes. 

PMID- 24101516
TI  - Identification and grafting of a unique peptide-binding site in the Fab framework
      of monoclonal antibodies.
AB  - Capitalizing on their extraordinary specificity, monoclonal antibodies (mAbs)
      have become one of the most reengineered classes of biological molecules. A major
      goal in many of these engineering efforts is to add new functionality to the
      parental mAb, including the addition of cytotoxins and imaging agents for medical
      applications. Herein, we present a unique peptide-binding site within the central
      cavity of the fragment antigen binding framework region of the chimeric, anti
      epidermal growth factor receptor mAb cetuximab. We demonstrate through
      diffraction methods, biophysical studies, and sequence analysis that this
      peptide, a meditope, has moderate affinity for the Fab, is specific to cetuximab
      (i.e., does not bind to human IgGs), and has no significant effect on antigen
      binding. We further demonstrate by diffraction studies and biophysical methods
      that the meditope binding site can be grafted onto the anti-human epidermal
      growth factor receptor 2 mAb trastuzumab, and that the antigen binding affinity
      of the grafted trastuzumab is indistinguishable from the parental mAb. Finally,
      we demonstrate a bivalent meditope variant binds specifically and stably to
      antigen-bearing cells only in the presence of the meditope-enabled mAbs.
      Collectively, this finding and the subsequent characterization and engineering
      efforts indicate that this unique interface could serve as a noncovalent "linker"
      for any meditope-enabled mAb with applications in multiple mAb-based technologies
      including diagnostics, imaging, and therapeutic delivery. 

PMID- 24101517
TI  - Mitochondrial disulfide relay mediates translocation of p53 and partitions its
      subcellular activity.
AB  - p53, a critical tumor suppressor, regulates mitochondrial respiration, but how a
      nuclear protein can orchestrate the function of an organelle encoded by two
      separate genomes, both of which require p53 for their integrity, remains unclear.
      Here we report that the mammalian homolog of the yeast mitochondrial disulfide
      relay protein Mia40 (CHCHD4) is necessary for the respiratory-dependent
      translocation of p53 into the mitochondria. In the setting of oxidative stress,
      increased CHCHD4 expression partitions p53 into the mitochondria and protects its
      genomic integrity while decreasing p53 nuclear localization and transcriptional
      activity. Conversely, decreased CHCHD4 expression prevents the mitochondrial
      translocation of p53 while augmenting its nuclear localization and activity.
      Thus, the mitochondrial disulfide relay system allows p53 to regulate two
      spatially segregated genomes depending on oxidative metabolic activity. 

PMID- 24101518
TI  - Water's second glass transition.
AB  - The glassy states of water are of common interest as the majority of H2O in space
      is in the glassy state and especially because a proper description of this
      phenomenon is considered to be the key to our understanding why liquid water
      shows exceptional properties, different from all other liquids. The occurrence of
      water's calorimetric glass transition of low-density amorphous ice at 136 K has
      been discussed controversially for many years because its calorimetric signature
      is very feeble. Here, we report that high-density amorphous ice at ambient
      pressure shows a distinct calorimetric glass transitions at 116 K and present
      evidence that this second glass transition involves liquid-like translational
      mobility of water molecules. This "double Tg scenario" is related to the
      coexistence of two liquid phases. The calorimetric signature of the second glass
      transition is much less feeble, with a heat capacity increase at Tg,2 about five
      times as large as at Tg,1. By using broadband-dielectric spectroscopy we resolve
      loss peaks yielding relaxation times near 100 s at 126 K for low-density
      amorphous ice and at 110 K for high-density amorphous ice as signatures of these
      two distinct glass transitions. Temperature-dependent dielectric data and heating
      rate-dependent calorimetric data allow us to construct the relaxation map for the
      two distinct phases of water and to extract fragility indices m = 14 for the low
      density and m = 20-25 for the high-density liquid. Thus, low-density liquid is
      classified as the strongest of all liquids known ("superstrong"), and also high
      density liquid is classified as a strong liquid. 

PMID- 24101519
TI  - Hypoxia-inducible factor 1 is required for remote ischemic preconditioning of the
      heart.
AB  - Both preclinical and clinical studies suggest that brief cycles of ischemia and
      reperfusion in the arm or leg may protect the heart against injury following
      prolonged coronary artery occlusion and reperfusion, a phenomenon known as remote
      ischemic preconditioning. Recent studies in mice indicate that increased plasma
      interleukin-10 (IL-10) levels play an important role in remote ischemic
      preconditioning induced by clamping the femoral artery for 5 min followed by 5
      min of reperfusion for a total of three cycles. In this study, we demonstrate
      that remote ischemic preconditioning increases plasma IL-10 levels and decreases
      myocardial infarct size in wild-type mice but not in littermates that are
      heterozygous for a knockout allele at the locus encoding hypoxia-inducible factor
      (HIF) 1alpha. Injection of a recombinant adenovirus encoding a constitutively
      active form of HIF-1alpha into mouse hind limb muscle was sufficient to increase
      plasma IL-10 levels and decrease myocardial infarct size. Exposure of C2C12 mouse
      myocytes to cyclic hypoxia and reoxygenation rapidly increased levels of IL-10
      mRNA, which was blocked by administration of the HIF-1 inhibitor acriflavine or
      by expression of short hairpin RNA targeting HIF-1alpha or HIF-1beta. Chromatin
      immunoprecipitation assays demonstrated that binding of HIF-1 to the Il10 gene
      was induced when myocytes were subjected to cyclic hypoxia and reoxygenation.
      Taken together, these data indicate that HIF-1 activates Il10 gene transcription
      and is required for remote ischemic preconditioning. 

PMID- 24101520
TI  - Allosteric regulation of SERCA by phosphorylation-mediated conformational shift
      of phospholamban.
AB  - The membrane protein complex between the sarcoplasmic reticulum Ca(2+)-ATPase
      (SERCA) and phospholamban (PLN) controls Ca(2+) transport in cardiomyocytes,
      thereby modulating cardiac contractility. beta-Adrenergic-stimulated
      phosphorylation of PLN at Ser-16 enhances SERCA activity via an unknown
      mechanism. Using solid-state nuclear magnetic resonance spectroscopy, we mapped
      the physical interactions between SERCA and both unphosphorylated and
      phosphorylated PLN in membrane bilayers. We found that the allosteric regulation
      of SERCA depends on the conformational equilibrium of PLN, whose cytoplasmic
      regulatory domain interconverts between three different states: a ground T state
      (helical and membrane associated), an excited R state (unfolded and membrane
      detached), and a B state (extended and enzyme-bound), which is noninhibitory.
      Phosphorylation at Ser-16 of PLN shifts the populations toward the B state,
      increasing SERCA activity. We conclude that PLN's conformational equilibrium is
      central to maintain SERCA's apparent Ca(2+) affinity within a physiological
      window. This model represents a paradigm shift in our understanding of SERCA
      regulation by posttranslational phosphorylation and suggests strategies for
      designing innovative therapeutic approaches to enhance cardiac muscle
      contractility. 

PMID- 24101521
TI  - Pooled RNAi screen identifies ubiquitin ligase Itch as crucial for influenza A
      virus release from the endosome during virus entry.
AB  - Influenza viruses, like other viruses, rely on host factors to support their life
      cycle as viral proteins usually "hijack," or collaborate with, cellular proteins
      to execute their functions. Identification and understanding of these factors can
      increase the knowledge of molecular mechanisms manipulated by the viruses and
      facilitate development of antiviral drugs. To this end, we developed a unique
      genome-wide pooled shRNA screen to search for cellular factors important for
      influenza A virus (IAV) replication. We identified an E3 ubiquitin ligase, Itch,
      as an essential factor for an early step in the viral life cycle. In Itch
      knockdown cells, the incorporation of viral ribonucleoprotein complex into
      endosomes was normal, but its subsequent release from endosomes and transport to
      the nucleus was retarded. In addition, upon virus infection, Itch was
      phosphorylated and recruited to the endosomes, where virus particles were
      located. Furthermore, Itch interacted with viral M1 protein and ubiquitinated M1
      protein. Collectively, our findings unravel a critical role of Itch in mediating
      IAV release from the endosome and offer insights into the mechanism for IAV
      uncoating during virus entry. These findings also highlight the feasibility of
      pooled RNAi screening for exploring the cellular cofactors of lytic viruses. 

PMID- 24101522
TI  - MicroRNA-23a promotes myelination in the central nervous system.
AB  - Demyelinating disorders including leukodystrophies are devastating conditions
      that are still in need of better understanding, and both oligodendrocyte
      differentiation and myelin synthesis pathways are potential avenues for
      developing treatment. Overexpression of lamin B1 leads to leukodystrophy
      characterized by demyelination of the central nervous system, and microRNA-23
      (miR-23) was found to suppress lamin B1 and enhance oligodendrocyte
      differentiation in vitro. Here, we demonstrated that miR-23a-overexpressing mice
      have increased myelin thickness, providing in vivo evidence that miR-23a enhances
      both oligodendrocyte differentiation and myelin synthesis. Using this mouse
      model, we explored possible miR-23a targets and revealed that the phosphatase and
      tensin homologue/phosphatidylinositol trisphosphate kinase/Akt/mammalian target
      of rapamycin pathway is modulated by miR-23a. Additionally, a long noncoding RNA,
      2700046G09Rik, was identified as a miR-23a target and modulates phosphatase and
      tensin homologue itself in a miR-23a-dependent manner. The data presented here
      imply a unique role for miR-23a in the coordination of proteins and noncoding
      RNAs in generating and maintaining healthy myelin. 

PMID- 24101523
TI  - Deficits in microRNA-mediated Cxcr4/Cxcl12 signaling in neurodevelopmental
      deficits in a 22q11 deletion syndrome mouse model.
AB  - 22q11 deletion syndrome (22q11DS) frequently accompanies psychiatric conditions,
      some of which are classified as schizophrenia and bipolar disorder in the current
      diagnostic categorization. However, it remains elusive how the chromosomal
      microdeletion leads to the mental manifestation at the mechanistic level. Here we
      show that a 22q11DS mouse model with a deletion of 18 orthologous genes of human
      22q11 (Df1/+ mice) has deficits in migration of cortical interneurons and
      hippocampal dentate precursor cells. Furthermore, Df1/+ mice show functional
      defects in Chemokine receptor 4/Chemokine ligand 12 (Cxcr4/Cxcl12; Sdf1)
      signaling, which reportedly underlie interneuron migration. Notably, the defects
      in interneuron progenitors are rescued by ectopic expression of Dgcr8, one of the
      genes in 22q11 microdeletion. Furthermore, heterozygous knockout mice for Dgcr8
      show similar neurodevelopmental abnormalities as Df1/+ mice. Thus, Dgcr8-mediated
      regulation of microRNA is likely to underlie Cxcr4/Cxcl12 signaling and
      associated neurodevelopmental defects. Finally, we observe that expression of
      CXCL12 is decreased in olfactory neurons from sporadic cases with schizophrenia
      compared with normal controls. Given the increased risk of 22q11DS in
      schizophrenia that frequently shows interneuron abnormalities, the overall study
      suggests that CXCR4/CXCL12 signaling may represent a common downstream mediator
      in the pathophysiology of schizophrenia and related mental conditions. 

PMID- 24101524
TI  - Cancer cell exosomes depend on cell-surface heparan sulfate proteoglycans for
      their internalization and functional activity.
AB  - Extracellular vesicle (EV)-mediated intercellular transfer of signaling proteins
      and nucleic acids has recently been implicated in the development of cancer and
      other pathological conditions; however, the mechanism of EV uptake and how this
      may be targeted remain as important questions. Here, we provide evidence that
      heparan sulfate (HS) proteoglycans (PGs; HSPGs) function as internalizing
      receptors of cancer cell-derived EVs with exosome-like characteristics.
      Internalized exosomes colocalized with cell-surface HSPGs of the syndecan and
      glypican type, and exosome uptake was specifically inhibited by free HS chains,
      whereas closely related chondroitin sulfate had no effect. By using several cell
      mutants, we provide genetic evidence of a receptor function of HSPG in exosome
      uptake, which was dependent on intact HS, specifically on the 2-O and N-sulfation
      groups. Further, enzymatic depletion of cell-surface HSPG or pharmacological
      inhibition of endogenous PG biosynthesis by xyloside significantly attenuated
      exosome uptake. We provide biochemical evidence that HSPGs are sorted to and
      associate with exosomes; however, exosome-associated HSPGs appear to have no
      direct role in exosome internalization. On a functional level, exosome-induced
      ERK1/2 signaling activation was attenuated in PG-deficient mutant cells as well
      as in WT cells treated with xyloside. Importantly, exosome-mediated stimulation
      of cancer cell migration was significantly reduced in PG-deficient mutant cells,
      or by treatment of WT cells with heparin or xyloside. We conclude that cancer
      cell-derived exosomes use HSPGs for their internalization and functional
      activity, which significantly extends the emerging role of HSPGs as key receptors
      of macromolecular cargo. 

PMID- 24101525
TI  - Conformational transitions during FtsK translocase activation of individual XerCD
      dif recombination complexes.
AB  - Three single-molecule techniques have been used simultaneously and in tandem to
      track the formation in vitro of single XerCD-dif recombination complexes. We
      observed the arrival of the FtsK translocase at individual preformed synaptic
      complexes and demonstrated the conformational change that occurs during their
      activation. We then followed the reaction intermediate transitions as Holliday
      junctions formed through catalysis by XerD, isomerized, and were converted by
      XerC to reaction products, which then dissociated. These observations, along with
      the calculated intermediate lifetimes, inform the reaction mechanism, which plays
      a key role in chromosome unlinking in most bacteria with circular chromosomes. 

PMID- 24101526
TI  - Granzyme B degradation by autophagy decreases tumor cell susceptibility to
      natural killer-mediated lysis under hypoxia.
AB  - Recent studies demonstrated that autophagy is an important regulator of innate
      immune response. However, the mechanism by which autophagy regulates natural
      killer (NK) cell-mediated antitumor immune responses remains elusive. Here, we
      demonstrate that hypoxia impairs breast cancer cell susceptibility to NK-mediated
      lysis in vitro via the activation of autophagy. This impairment was not related
      to a defect in target cell recognition by NK cells but to the degradation of NK
      derived granzyme B in autophagosomes of hypoxic cells. Inhibition of autophagy by
      targeting beclin1 (BECN1) restored granzyme B levels in hypoxic cells in vitro
      and induced tumor regression in vivo by facilitating NK-mediated tumor cell
      killing. Together, our data highlight autophagy as a mechanism underlying the
      resistance of hypoxic tumor cells to NK-mediated lysis. The work presented here
      provides a cutting-edge advance in our understanding of the mechanism by which
      hypoxia-induced autophagy impairs NK-mediated lysis in vitro and paves the way
      for the formulation of more effective NK cell-based antitumor therapies. 

PMID- 24101527
TI  - Obesity increases length of stay and direct medical costs in total hip
      arthroplasty.
AB  - BACKGROUND: The number of obese patients undergoing THA is increasing. Previous
      studies have shown that obesity is associated with an increased likelihood of
      complications after THA, but there is little information regarding the impact of
      obesity on medical resource use and direct medical costs in THA.
      QUESTIONS/PURPOSES: We sought to examine the relationship between obesity, length
      of stay, and direct medical costs in a large cohort of patients undergoing THAs.
      METHODS: The study included 8973 patients who had undergone 6410 primary and 2563
      revision THAs at a large US medical center between January 1, 2000, and September
      31, 2008. Patients with bilateral procedures within 90 days after index admission
      and patients with acute trauma were excluded. Data regarding clinical, surgical
      characteristics, and complications were obtained from the original medical
      records and the institutional joint registry. Patients were classified into eight
      groups based on their BMI at the time of surgery. Direct medical costs were
      calculated by using standardized, inflation-adjusted costs for services and
      procedures billed during hospitalization and the 90-day window. Study end points
      were hospital length of stay, direct medical costs during hospitalization, and
      the 90-day window. End points were compared across the eight BMI categories in
      multivariable risk-adjusted linear regression models. RESULTS: Mean length of
      stay and the direct medical costs were lowest for patients with a BMI of 25 to 35
      kg/m(2). Increasing BMI was associated with longer hospital stays and costs.
      Every five-unit increase in BMI beyond 30 kg/m(2) was associated with
      approximately USD $500 higher hospital costs and USD $900 higher 90-day costs in
      primary THA (p = 0.0001), which corresponded to 5% higher costs. The cost
      increase associated with BMI was greater in the revision THA cohort where every
      five-unit increase in BMI beyond 30 kg/m(2) was associated with approximately USD
      $800 higher hospital costs and USD $1500 higher 90-day costs. These estimates
      remained unchanged after adjusting for comorbidities or complications.
      CONCLUSIONS: Obesity is associated with longer hospital stays and higher costs in
      THA. The significant effect of obesity on costs persists even among patients
      without comorbidities but the increased costs associated with obesity may be
      balanced by the potential benefits of THA in the obese. Increasing prevalence of
      obesity likely contributes to the increasing financial burden of THA worldwide.
      LEVEL OF EVIDENCE: Level IV, economic and decision analyses. See the Instructions
      for Authors for a complete description of levels of evidence.

PMID- 24101528
TI  - Editor's Spotlight/Take 5: Death, taxes, and trapeziometacarpal arthrosis.
      Interview by Seth S. Leopold.

PMID- 24101529
TI  - In vitro maturation in subfertile women with polycystic ovarian syndrome
      undergoing assisted reproduction.
AB  - BACKGROUND: Polycystic ovarian syndrome (PCOS) occurs in 4% to 7% of all women of
      reproductive age and 50% of women presenting with subfertility. Subfertility
      affects 15% to 20% of couples trying to conceive. A significant proportion of
      these women ultimately need assisted reproductive technology (ART). In vitro
      fertilisation (IVF) is one of the assisted reproduction techniques employed to
      raise the chances of achieving a pregnancy. For the standard IVF technique,
      stimulating follicle development and growth before oocyte retrieval is essential,
      for which a large number of different methods combining gonadotrophins with a
      gonadotrophin-releasing hormone (GnRH) agonist or antagonist are used. In women
      with PCOS, the supra-physiological doses of gonadotrophins used for controlled
      ovarian hyperstimulation (COH) often result in an exaggerated ovarian response,
      characterised by the development of a large cohort of follicles of uneven
      quality, retrieval of immature oocytes, and increased risk of ovarian
      hyperstimulation syndrome. A potentially effective intervention for women with
      PCOS-related subfertility involves earlier retrieval of immature oocytes at the
      germinal-vesicle stage followed by in vitro maturation (IVM). So far, the only
      data available have derived from observational studies and non-randomised
      clinical trials. OBJECTIVES: To compare outcomes associated with in vitro
      maturation (IVM) followed by vitro fertilisation (IVF) or intracytoplasmic sperm
      injection (ICSI) versus conventional IVF or ICSI, among women with polycystic
      ovarian syndrome (PCOS) undergoing assisted reproductive technologies (ART).
      SEARCH METHODS: We searched the Menstrual Disorders and Subfertility Group (MDSG)
      Specialised Register of controlled trials to May 2013 for any relevant trials
      identified from the title, abstract, or keyword sections. This was followed by a
      search of the electronic database MEDLINE, EMBASE, LILACS and CINAHL, without
      language restriction. We also performed a manual search of the references of all
      retrieved articles; sought unpublished papers and abstracts submitted to
      international conferences, searched the clinicaltrials.gov and WHO portal
      registries for submitted protocols of clinical trials, and contacted experts. In
      addition, we examined the National Institute of Clinical Excellence (NICE)
      fertility assessment and treatment guidelines and handsearched reference lists of
      relevant articles (from 1970 to May 2013). SELECTION CRITERIA: All randomised
      trials (RCTs) on the intention to perform IVM before IVF or ICSI compared with
      conventional IVF or ICSI for subfertile women with PCOS. DATA COLLECTION AND
      ANALYSIS: Three review authors (CS, MK and NV) independently assessed eligibility
      and quality of trials. Primary outcome measure was live birth rate per randomised
      woman. MAIN RESULTS: There were no RCTs suitable for inclusion in the review,
      although there are currently three ongoing trials that have not yet reported
      results. AUTHORS' CONCLUSIONS: Though promising data on the IVM technique have
      been published, unfortunately there is still no evidence from RCTs upon which to
      base any practice recommendations regarding IVM before IVF or ICSI for women with
      PCOS. Meanwhile, the results of the above-mentioned ongoing trials are awaited
      and, of course, further evidence from good quality trials in the field is eagerly
      anticipated.

PMID- 24101530
TI  - Erratum to: Learned predictiveness effects following single-cue training in
      humans.

PMID- 24101531
TI  - The prevalence of harmful and hazardous alcohol consumption in older U.S. adults:
      data from the 2005-2008 National Health and Nutrition Examination Survey
      (NHANES).
AB  - BACKGROUND: Alcohol consumption and its interaction with disease, medication use,
      and functional status may result in serious health problems, but little
      information exists about the national prevalence of alcohol-related health risk
      in older adults. OBJECTIVE: To estimate the prevalence of harmful and hazardous
      alcohol use and the prevalence of consumption in excess of National Institute of
      Alcohol Abuse and Alcoholism (NIAAA) recommendations, in people aged 65 and
      older, and by sex and race/ethnicity sub-group. DESIGN: Cross-sectional, using
      data from the 2005-2008 National Health and Nutrition Examination Survey of the
      non-institutionalized U.S. population. PARTICIPANTS: One thousand and eighty
      three respondents aged 65 and older who consume alcohol. MAIN MEASURES:
      Participants' alcohol consumption was classified as Harmful, Hazardous, or
      Healthwise, in the context of their specific health status, using the Alcohol
      Related Problems Survey classification algorithm. KEY RESULTS: Overall, 14.5 % of
      older drinkers (95 % CI: 12.1 %, 16.8 %) consumed alcohol above the NIAAA's
      recommended limits. However, when health status was taken into account, 37.4 % of
      older drinkers (95 % CI: 34.9 %, 40.0 %) had Harmful consumption and 53.3 % (95 %
      CI: 50.1 %, 56.6 %) had either Hazardous or Harmful consumption. Among
      light/moderate drinkers, the proportions were 17.7 % (95 % CI: 14.7 %, 20.7 %)
      and 28.0 % (95 % CI: 24.8 %, 31.1 %), respectively. Male drinkers had
      significantly greater odds of Hazardous/Harmful consumption than female drinkers
      (OR = 2.14 [95 % CI: 1.77, 2.6]). Black drinkers had worse health status and
      significantly greater odds of Hazardous/Harmful consumption than white drinkers
      (OR = 1.49; 95 % CI: 1.02, 2.17), despite having no greater prevalence of
      drinking in excess of NIAAA-recommended limits. CONCLUSION: Most older Americans
      who drink are light/moderate drinkers, yet substantial proportions of such
      drinkers drink in a manner that is either harmful or hazardous to their health.
      Older adults with risky alcohol consumption are unlikely to be identified by
      health care providers if clinicians rely solely on whether patient consumption
      exceeds the NIAAA-recommended limits.

PMID- 24101532
TI  - Home visits.

PMID- 24101533
TI  - A cross-sectional study examining Australian general practitioners'
      identification of overweight and obese patients.
AB  - BACKGROUND: Overweight and obese patients attempt weight loss when advised to do
      so by their physicians; however, only a small proportion of these patients report
      receiving such advice. One reason may be that physicians do not identify their
      overweight and obese patients. OBJECTIVES: We aimed to determine the extent that
      Australian general practitioners (GP) recognise overweight or obesity in their
      patients, and to explore patient and GP characteristics associated with non
      detection of overweight and obesity. METHODS: Consenting adult patients (n =
      1,111) reported weight, height, demographics and health conditions using a
      touchscreen computer. GPs (n = 51) completed hard-copy questionnaires indicating
      whether their patients were overweight or obese. We calculated the sensitivity,
      specificity, positive predictive value (PPV) and negative predictive value (NPV)
      for GP detection, using patient self-reported weight and height as the criterion
      measure for overweight and obesity. For a subsample of patients (n = 107), we did
      a sensitivity analysis with patient-measured weight and height. We conducted an
      adjusted, multivariable logistic regression to explore characteristics associated
      with non-detection, using random effects to adjust for correlation within GPs.
      RESULTS: Sensitivity for GP assessment was 63 % [95 % CI 57-69 %], specificity 89
      % [95 % CI 85-92 %], PPV 87 % [95 % CI 83-90 %] and NPV 69 % [95 % CI 65-72 %].
      Sensitivity increased by 3 % and specificity was unchanged in the sensitivity
      analysis. Men (OR: 1.7 [95 % CI 1.1-2.7]), patients without high blood pressure
      (OR: 1.8 [95 % CI 1.2-2.8]) and without type 2 diabetes (OR: 2.4 [95 % CI 1.2
      8.0]) had higher odds of non-detection. Individuals with obesity (OR: 0.1 [95 %
      CI 0.07-0.2]) or diploma-level education (OR: 0.3 [95%CI 0.1-0.6]) had lower odds
      of not being identified. No GP characteristics were associated with non-detection
      of overweight or obesity. CONCLUSIONS: GPs missed identifying a substantial
      proportion of overweight and obese patients. Strategies to support GPs in
      identifying their overweight or obese patients need to be implemented.

PMID- 24101535
TI  - Capsule commentary on Wilhelm-Leen et al., phase angle, frailty and mortality in
      older adults.

PMID- 24101534
TI  - Trends in insulin initiation and treatment intensification among patients with
      type 2 diabetes.
AB  - BACKGROUND: Many patients with type 2 diabetes eventually require insulin, yet
      little is known about the patterns and quality of pharmacologic care received
      following insulin initiation. Guidelines from the American Diabetes Association
      and the European Association for the Study of Diabetes recommend that insulin
      secretagogues such as sulfonylureas be discontinued at the time of insulin
      initiation to reduce the risk of hypoglycemia, and that treatment be intensified
      if HbA1c levels remain above-target 3 months after insulin initiation. OBJECTIVE:
      To describe pharmacologic treatment patterns over time among adults initiating
      insulin and/or intensifying insulin treatment. DESIGN: Observational study.
      SUBJECTS: A large commercially insured population of adult patients without
      recorded type 1 diabetes who initiated insulin. MAIN MEASURES: We evaluated
      changes in non-insulin antidiabetic medication use during the 120 days
      immediately following insulin initiation, rates of increase in insulin dose
      and/or dosing frequency during the 270 days following an insulin initiation
      treatment period of 90 days, and rates of insulin discontinuation. KEY RESULTS:
      Seven thousand, nine hundred and thirty-two patients initiated insulin during
      2003-2008, with the majority (61 %) initiating basal insulin only. Metformin (55
      %), sulfonylureas (39 %), and thiazolidinediones (30 %) were commonly used prior
      to insulin initiation. Metformin was continued by 64 % of patients following
      mixed or mealtime insulin initiation; the continuation rate was nearly as high
      for sulfonylureas (58 %). Insulin dose and/or dosing frequency increased among
      22.9 % of patients. Insulin was discontinued by 27 % of patients. CONCLUSIONS: We
      found evidence of substantial departures from guideline-recommended
      pharmacotherapy. Insulin secretagogues were frequently co-prescribed with
      insulin. The majority of patients had no evidence of treatment intensification
      following insulin initiation, although this finding is difficult to interpret
      without HbA1c levels. While each patient's care should be individualized, our
      data suggest that the quality of care following insulin initiation can be
      improved.

PMID- 24101537
TI  - Toward a social theory of sexual risk behavior among men in the Armed Services:
      understanding the military occupational habitus.
AB  - Worldwide, military personnel have been recognized as a population at elevated
      risk for sexually transmitted infections (STIs) and HIV; however, it is not well
      understood how the military occupation itself is implicated in the production of
      sexual risk behavior. Using qualitative and quantitative data collected from the
      Belize Defense Force (BDF), we employed a grounded theoretical framework and the
      Bourdieusian concept of the field and habitus to clarify how the military
      occupation is implicated in structuring aspects of sexual risk behaviors among
      personnel. We focus results on in-depth qualitative interviews conducted with 15
      male-identified BDF personnel. We identify and describe how two field elements,
      namely operational tempo and ongoing exposure to occupational hazards, are
      occupationally specific field elements implicated in the production of sexual
      risk behavior through the mediating matrix of the military class habitus. Our
      findings demonstrate a conceptual clarity regarding the institutional field and
      habitus through which military personnel make sense of and act on the risk of
      bodily harm with regard to their own sexual behaviors. We conclude by outlining
      our theoretical concept so that it can be directly applied in public health
      efforts in order to leverage military occupational field elements for the purpose
      of HIV and STI prevention. 

PMID- 24101538
TI  - "Now he walks and walks, as if he didn't have a home where he could eat": food,
      healing, and hunger in Quechua narratives of madness.
AB  - In the Quechua-speaking peasant communities of southern Peru, mental disorder is
      understood less as individualized pathology and more as a disturbance in family
      and social relationships. For many Andeans, food and feeding are ontologically
      fundamental to such relationships. This paper uses data from interviews and
      participant observation in a rural province of Cuzco to explore the significance
      of food and hunger in local discussions of madness. Carers' narratives,
      explanatory models, and theories of healing all draw heavily from idioms of food
      sharing and consumption in making sense of affliction, and these concepts
      structure understandings of madness that differ significantly from those assumed
      by formal mental health services. Greater awareness of the salience of these
      themes could strengthen the input of psychiatric and psychological care with this
      population and enhance knowledge of the alternative treatments that they use.
      Moreover, this case provides lessons for the global mental health movement on the
      importance of openness to the ways in which indigenous cultures may construct
      health, madness, and sociality. Such local meanings should be considered by
      mental health workers delivering services in order to provide care that can
      adjust to the alternative ontologies of sufferers and carers. 

PMID- 24101539
TI  - Impact of vendor computerized physician order entry on patients with renal
      impairment in community hospitals.
AB  - BACKGROUND: Adverse drug events (ADEs) are common among hospitalized patients
      with renal impairment. OBJECTIVE: To determine whether computerized physician
      order entry (CPOE) systems with clinical decision support capabilities reduce the
      frequency of renally related ADEs in hospitals. DESIGN, SETTING, AND PATIENTS:
      Quasi-experimental study of 1590 adult patients with renal impairment who were
      admitted to 5 community hospitals in Massachusetts from January 2005 to September
      2010, preimplementation and postimplementation of CPOE. INTERVENTION: Varying
      levels of clinical decision support, ranging from basic CPOE only (sites 4 and
      5), rudimentary clinical decision support (sites 1 and 2), and advanced clinical
      decision support (site 3). MEASUREMENTS: Primary outcome was the rate of
      preventable ADEs from nephrotoxic and/or renally cleared medications. Similarly,
      secondary outcomes were the rates of overall ADEs and potential ADEs. KEY
      RESULTS: There was a 45% decrease in the rate of preventable ADEs following
      implementation (8.0/100 vs 4.4/100 admissions; P < 0.01), and the impact was
      related to the level of decision support. Basic CPOE was not associated with any
      significant benefit (4.6/100 vs 4.3/100 admissions; P = 0.87). There was a
      nonsignificant decrease in preventable ADEs with rudimentary clinical decision
      support (9.1/100 vs 6.4/100 admissions; P = 0.22). However, substantial reduction
      was seen with advanced clinical decision support (12.4/100 vs 0/100 admissions; P
      = 0.01). Despite these benefits, a significant increase in potential ADEs was
      found for all systems (55.5/100 vs 136.8/100 admissions; P < 0.01). CONCLUSION:
      Vendor-developed CPOE with advanced clinical decision support can reduce the
      occurrence of preventable ADEs but may be associated with an increase in
      potential ADEs.

PMID- 24101540
TI  - The effect of inpatient stress testing on subsequent emergency department visits,
      readmissions, and costs.
AB  - BACKGROUND: Patients with low-risk chest pain are frequently readmitted for
      evaluation of recurrent chest pain. It is unknown whether stress testing during
      the first admission for chest pain is a cost-effective means of reducing
      readmissions. METHODS: Using a hospital administrative database, we conducted a
      retrospective cohort study of patients aged >=18 years admitted under
      "observation status" to Baystate Medical Center between January 2007 and July
      2009 for chest pain without acute coronary syndrome. We compared subsequent
      emergency department (ED) visits, readmissions, and costs within 1 year for
      patients who had a stress test at index admission to those who did not, adjusting
      for age, gender, race, insurance, and comorbidities. RESULTS: The cohort included
      3315 patients. Most (n = 2376, 71.7%) had a stress test during the index
      admission. Within 1 year, 256 (7.7%) patients returned to the ED at least once
      with chest pain. Of these, 112 (43.8%) were admitted during their first return
      visit. In the multivariable model, return visits for chest pain were negatively
      associated with previous stress testing (odds ratio [OR]: 0.6, 95% confidence
      interval [CI]: 0.5 to 0.9). Once in the ED, however, the risk of admission did
      not vary by stress test during index admission (OR: 0.8, 95% CI: 0.4 to 1.4).
      Overall costs, including index admission and follow-up visits for chest pain,
      were higher for patients with stress testing at index admission. CONCLUSION:
      Inpatient stress testing reduced subsequent resource utilization in terms of ED
      visits and resultant readmissions, but the savings were not enough to offset the
      cost of initial testing.

PMID- 24101541
TI  - Evaluation of venous thromboembolism prophylaxis in patients with chronic liver
      disease.
AB  - BACKGROUND: The incidence of venous thromboembolism (VTE) in chronic liver
      disease (CLD) patients has been reported to be 0.5% to 6.3%. Studies report the
      use of thromboprophylaxis in CLD patients as suboptimal, with at least 75% of
      patients receiving no prophylaxis. OBJECTIVE: To describe the use of VTE
      prophylaxis in CLD patients. DESIGN: A retrospective review. SETTING: Tertiary
      care academic medical center. PATIENTS: Inpatient admissions from August 2009
      through July 2011 with CLD diagnosis. INTERVENTION: None. MEASUREMENTS:
      Initiation and type of thromboprophylaxis, incidence of VTE, bleeding events,
      hospital length of stay, in-hospital mortality, 30-day readmission for VTE.
      RESULTS: Of the 410 patients included, 225 (55%) patients received
      thromboprophylaxis. For patients with international normalized ratio (INR) >2.0,
      a significant decrease in overall thromboprophylaxis use and pharmacologic
      prophylaxis use was seen compared to those with INR 1.4 to 2.0 (P = 0.013 and P <
      0.001, respectively). Overall incidence of VTE was 0.7%. Fifteen bleeding events
      occurred (3.7%): 9 on mechanical prophylaxis, 1 on pharmacologic, 3 on
      combination, and 2 with no prophylaxis. The majority of patients experiencing a
      bleeding event had an INR >2.0 (P = 0.001). CONCLUSION: The use of
      thromboprophylaxis in CLD patients is higher in our study than previous reports
      but remains suboptimal. Use of VTE pharmacologic prophylaxis does not appear to
      increase bleeding in CLD patients with INR <=2.0. Further studies are needed to
      provide additional safety data.

PMID- 24101542
TI  - Discharge against medical advice: how often do we intervene?
AB  - BACKGROUND: Discharges against medical advice (AMA) occur in 1% to 2% of hospital
      stays and are associated with increased morbidity, readmission rates, and 30-day
      mortality. Risk factors associated with AMA have been investigated, but
      interventions at the time of discharge have not been carefully examined. METHODS:
      We retrospectively reviewed the records of adult patients discharged AMA over a 2
      year period from the general medical service of a university-affiliated tertiary
      care hospital. We assessed for presence of documentation addressing informed
      consent, patient decision-making capacity, health literacy, follow-up plans,
      whether medications were prescribed, and whether any warning indicators of
      impending AMA were apparent. RESULTS: Two hundred ninety-one records were
      reviewed. AMA notes were present in 276 (94.8%) charts. Notes were authored by
      physicians in 163 (59.1%) and nurses in 110 (37.8%) encounters. Informed consent
      was present in 88 (30.2%) charts, mentioned in the note but not present in the
      chart in 111 (38.1%), and not signed in 92 (31.6%) charts. Decision-making
      capacity and health literacy were documented in 108 (37.1%) and 75 (25.8%)
      records, respectively. Warning of impending AMA was present in 217 (74.6%)
      charts. Medications prescribed and follow-up plans were documented in 71 (24.4%)
      and 91 (31.3%) charts, respectively. CONCLUSIONS: Advance warning of impending
      AMA is often present, yet only a minority of cases have prescription of
      medications or development of follow-up plans. Medical documentation of AMA
      dispositions is frequently inadequate, suggesting missed opportunities to
      intervene as well as suboptimal medicolegal scenarios.

PMID- 24101543
TI  - Postdischarge clinics: hospitalist attitudes and experiences.
AB  - Novel methods for improving transitions of care are needed. Hospitalist-run
      postdischarge clinics (PDCs) may improve access to postdischarge care, but
      require practice change from providers. We conducted a Web-based cross-sectional
      survey of hospitalists at 37 academic medical centers across the United States
      and a large private employer of hospitalists to assess the attitudes of
      hospitalists toward postdischarge care and PDCs. Two hundred twenty-eight of 814
      hospitalists responded to the survey (28%). Responding hospitalists commonly
      (55%) experienced difficulty arranging outpatient follow-up, and felt that lack
      of access was responsible for most patient problems after discharge (61%).
      Despite this, 62% felt hospitalists should not provide postdischarge care in a
      clinic, and 77% felt they would require extra compensation for work in a PDC.
      However, 74% thought such a clinic would decrease emergency department visits.
      Practicing in a PDC was associated with a trend toward positive attitudes about
      providing postdischarge care (P = 0.054). Responding hospitalists expressed
      difficulty arranging appropriate postdischarge care, confidence that PDCs would
      reduce postdischarge utilization, and reservations about working in a PDC,
      perhaps because of practical or financial concerns. These results are important
      given the current emphasis on reducing hospital readmissions. Further work
      evaluating the experience of hospitalists in PDCs is needed.

PMID- 24101545
TI  - Lymph node ratio and breast cancer prognosis: a meta-analysis.
AB  - Due to the heterogeneity of lymph node examination and the conflicting results
      existing for the same classification of lymph node ratio (LNR), it is necessary
      to conduct a meta-analysis to evaluate the prognostic effects of different LNRs
      on breast cancer. PubMed, EMBASE, and ISI Web of Knowledge were searched to find
      all published cohort studies that evaluated the prognostic value of different
      LNRs on breast cancer. The outcomes were overall survival (OS), disease-free
      survival (DFS), breast cause-special survival (BCCS), mortality, locoregional
      recurrence (LRR), and distant metastasis. Data was analyzed using comprehensive
      meta-analysis software version 2.0, and 23 studies were included. The available
      evidence showed that LNR was a prognostic predictor for breast cancer, especially
      for clinically node-positive breast cancer, but the available evidence could not
      judge which cutoff point is the most reliable. Meanwhile, the cutoff values 0.2
      and 0.65 could be suitable to predict breast cancer OS, DFS, BCCS, and mortality.

PMID- 24101544
TI  - Provider-to-provider electronic communication in the era of meaningful use: a
      review of the evidence.
AB  - BACKGROUND: Electronic communication between providers occurs daily in clinical
      practice but has not been well studied. PURPOSE: To assess the impact of provider
      to-provider electronic communication tools on communication and healthcare
      outcomes through literature review. DATA SOURCES: Ovid MEDLINE, PubMed, Google
      Scholar, Cumulative Index to Nursing and Allied Health Literature, and Academic
      Search Premier. STUDY SELECTION: Publication in English-language peer-reviewed
      journals. Studies provided quantitative provider-to-provider communication data,
      provider satisfaction statistics, or electronic health record (EHR) communication
      data. DATA EXTRACTION: Literature review. DATA SYNTHESIS: Two reviewers conducted
      the title review to determine eligible studies from initial search results. Three
      reviewers independently reviewed titles, abstracts, and full text (where
      appropriate) against inclusion and exclusion criteria. LIMITATIONS: Small number
      of eligible studies; few described trial design (20%). Homogeneous provider type
      (physicians). English-only studies. CONCLUSIONS: Of 25 included studies, all
      focused on physicians; most were observational (68%). Most (60%) described
      electronic specialist referral tools. Although overall use has been measured,
      there were no studies of the effectiveness of intra-EHR messaging. Literature
      describing the effectiveness of provider-to-provider electronic communications is
      sparse and narrow in scope. Complex care, such as that envisioned for the Patient
      Centered Medical Home, necessitates further research.

PMID- 24101546
TI  - Ultrasonographic findings of missed breast cancer: pitfalls and pearls.
AB  - Breast ultrasonography (US) is an indispensable tool for diagnosis of palpable
      and non-palpable breast masses and can facilitate good patient care for breast
      cancer. However, it is of limited value in cases of isoechoic lesions surrounded
      by fat, heterogeneous echoic lesions surrounded by a heterogeneous background,
      deep lesions in huge breasts, subareolar lesions, and lesions caused by poor and
      underdeveloped operator skills. Some breast tumors such as ductal carcinoma in
      situ and invasive lobular carcinoma are easily missed on US because of the nature
      of the lesions. Recent studies have emphasized the use of tools complementary to
      B-mode US, including real-time elastography and Doppler imaging, in the
      evaluation of breast lesions missed on US. Radiologists can take a number of
      steps that will enhance the accuracy of US image interpretation and decrease the
      rate of false-negative findings. These steps include reviewing
      clinicopathological data, using mammography and MRI to help assess breast lesions
      missed on US, strictly adhering to positioning and technical requirements, being
      alert to subtle features of missed breast lesions, and judging a lesion by its
      most malignant feature. 

PMID- 24101547
TI  - Asymptomatic HLA-A*02:01-restricted epitopes from herpes simplex virus
      glycoprotein B preferentially recall polyfunctional CD8+ T cells from
      seropositive asymptomatic individuals and protect HLA transgenic mice against
      ocular herpes.
AB  - Evidence from C57BL/6 mice suggests that CD8(+) T cells, specific to the
      immunodominant HSV-1 glycoprotein B (gB) H-2(b)-restricted epitope (gB498-505),
      protect against ocular herpes infection and disease. However, the possible role
      of CD8(+) T cells, specific to HLA-restricted gB epitopes, in protective immunity
      seen in HSV-1-seropositive asymptomatic (ASYMP) healthy individuals (who have
      never had clinical herpes) remains to be determined. In this study, we used
      multiple prediction algorithms to identify 10 potential HLA-A*02:01-restricted
      CD8(+) T cell epitopes from the HSV-1 gB amino acid sequence. Six of these
      epitopes exhibited high-affinity binding to HLA-A*02:01 molecules. In 10
      sequentially studied HLA-A*02:01-positive, HSV-1-seropositive ASYMP individuals,
      the most frequent, robust, and polyfunctional CD8(+) T cell responses, as
      assessed by a combination of tetramer, IFN-gamma-ELISPOT, CFSE proliferation,
      CD107a/b cytotoxic degranulation, and multiplex cytokine assays, were directed
      mainly against epitopes gB342-350 and gB561-569. In contrast, in 10 HLA-A*02:01
      positive, HSV-1-seropositive symptomatic (SYMP) individuals (with a history of
      numerous episodes of recurrent clinical herpes disease) frequent, but less
      robust, CD8(+) T cell responses were directed mainly against nonoverlapping
      epitopes (gB183-191 and gB441-449). ASYMP individuals had a significantly higher
      proportion of HSV-gB-specific CD8(+) T cells expressing CD107a/b degranulation
      marker and producing effector cytokines IL-2, IFN-gamma, and TNF-alpha than did
      SYMP individuals. Moreover, immunization of a novel herpes-susceptible HLA
      A*02:01 transgenic mouse model with ASYMP epitopes, but not with SYMP epitopes,
      induced strong CD8(+) T cell-dependent protective immunity against ocular herpes
      infection and disease. These findings should guide the development of a safe and
      effective T cell-based herpes vaccine. 

PMID- 24101548
TI  - Exogenous OX40 stimulation during lymphocytic choriomeningitis virus infection
      impairs follicular Th cell differentiation and diverts CD4 T cells into the
      effector lineage by upregulating Blimp-1.
AB  - T cell costimulation is a key component of adaptive immunity to viral infection
      but has also been associated with pathology because of excessive or altered T
      cell activity. We recently demonstrated that the TNFR family costimulatory
      molecule OX40 (CD134) is critically required to sustain antiviral T cell and Ab
      responses that enable control of viral replication in the context of chronic
      lymphocytic choriomeningitis virus (LCMV) infection. In this study, we
      investigated whether reinforcing OX40 stimulation through an agonist Ab had the
      potential to prevent LCMV persistence. We observed that anti-OX40 injection early
      after LCMV clone 13 infection increased CD8 T cell-mediated immunopathology. More
      strikingly, OX40 stimulation of virus-specific CD4 T cells promoted expression of
      the transcriptional repressor Blimp-1 and diverted the majority of cells away
      from follicular Th cell differentiation. This occurred in both acute and chronic
      infections, and resulted in dramatic reductions in germinal center and Ab
      responses to the viral infection. The effect of the OX40 agonist was dependent on
      IL-2 signaling and the timing of OX40 stimulation. Collectively, our data
      demonstrate that excessive OX40 signaling can result in deleterious consequences
      in the setting of LCMV infection. 

PMID- 24101549
TI  - SOCS3 deletion in T lymphocytes suppresses development of chronic ocular
      inflammation via upregulation of CTLA-4 and expansion of regulatory T cells.
AB  - Suppressors of cytokine signaling (SOCS) proteins are negative-feedback
      regulators of the JAK/STAT pathway, and SOCS3 contributes to host immunity by
      regulating the intensity and duration of cytokine signals and inflammatory
      responses. Mice with Socs3 deletion in myeloid cells exhibit enhanced STAT3
      signaling, expansion of Th1 and Th17 cells, and develop severe experimental
      autoimmune encephalomyelitis. Interestingly, development of the unique IL-17/IFN
      gamma double-producing (Th17/IFN-gamma and Tc17/IFN-gamma) subsets that exhibit
      strong cytotoxic activities and are associated with pathogenesis of several
      autoimmune diseases has recently been shown to depend on epigenetic suppression
      of SOCS3 expression, further suggesting involvement of SOCS3 in autoimmunity and
      tumor immunity. In this study, we generated mice with Socs3 deletion in the CD4 T
      cell compartment (CD4-SOCS3 knockout [KO]) to determine in vivo effects of the
      loss of Socs3 in the T cell-mediated autoimmune disease, experimental autoimmune
      uveitis (EAU). In contrast to the exacerbation of experimental autoimmune
      encephalomyelitis in myeloid-specific SOCS3-deleted mice, CD4-SOCS3KO mice were
      protected from acute and chronic uveitis. Protection from EAU correlated with
      enhanced expression of CTLA-4 and expansion of IL-10-producing regulatory T cells
      with augmented suppressive activities. We further show that SOCS3 interacts with
      CTLA-4 and negatively regulates CTLA-4 levels in T cells, providing a mechanistic
      explanation for the expansion of regulatory T cells in CD4-SOCS3 during EAU.
      Contrary to in vitro epigenetic studies, Th17/IFN-gamma and Tc17/IFN-gamma
      populations were markedly reduced in CD4-SOCS3KO, suggesting that SOCS3 promotes
      expansion of the Th17/IFN-gamma subset associated with development of severe
      uveitis. Thus, SOCS3 is a potential therapeutic target in uveitis and other
      autoinflammatory diseases. 

PMID- 24101550
TI  - STAT-3 activation by differential cytokines is critical for human in vivo
      generated plasma cell survival and Ig secretion.
AB  - Maturation and survival of plasma cells (PCs) depends on extrinsic factors
      provided in specialized niches. In addition, B lymphocyte differentiation into
      PCs requires the activation of the JAK-STAT-3 pathway. However, whether STAT-3 is
      needed only during the transition of B lymphocytes to PC, or it is also involved
      in the survival and function of PCs at different stages of maturation, has not
      been unequivocally clarified. This study analyzes the effect of IL-10, IL-21, and
      IL-6 on human in vivo-generated PCs isolated from secondary lymphoid organs,
      blood (circulating, recently Ag-induced PCs), and bone marrow. PCs from these
      different organs show specific profiles of receptors for, and responsiveness to,
      these cytokines required for their survival and sustained Ab secretion. However,
      IL-10, IL-21, and IL-6 commonly induce STAT-3 phosphorylation in the three PC
      subsets, and all of their effects are exerted strictly through the STAT-3
      activation. The inhibition or nonactivation of this pathway in the three PC
      populations impairs not only the effect of STAT-3-activating cytokines, but also
      the action of other cytokines important at the PC level, including a
      proliferation-induced ligand, BAFF, insulin-like growth factor 1, vascular
      endothelial growth factor, and stromal cell-derived factor-1alpha. These results
      indicate that STAT-3 activation is critical for human PCs throughout their
      maturation. 

PMID- 24101551
TI  - T cell-independent modulation of experimental autoimmune encephalomyelitis in
      ADAP-deficient mice.
AB  - The adhesion- and degranulation-promoting adaptor protein (ADAP), expressed in T
      cells, myeloid cells, and platelets, is known to regulate receptor-mediated
      inside-out signaling leading to integrin activation and adhesion. In this study,
      we demonstrate that, upon induction of active experimental autoimmune
      encephalomyelitis (EAE) by immunization with the myelin oligodendrocyte
      glycoprotein35-55 peptide, ADAP-deficient mice developed a significantly milder
      clinical course of EAE and showed markedly less inflammatory infiltrates in the
      CNS than wild-type mice. Moreover, ADAP-deficient recipients failed to induce EAE
      after adoptive transfer of myelin oligodendrocyte glycoprotein-specific TCR
      transgenic T cells (2D2 T cells). In addition, ex vivo fully activated 2D2 T
      cells induced significantly less severe EAE in ADAP-deficient recipients. The
      ameliorated disease in the absence of ADAP was not due to expansion or deletion
      of a particular T cell subset but rather because of a strong reduction of all
      inflammatory leukocyte populations invading the CNS. Monitoring the adoptively
      transferred 2D2 T cells over time demonstrated that they accumulated within the
      lymph nodes of ADAP-deficient hosts. Importantly, transfer of complete wild-type
      bone marrow or even bone marrow of 2D2 TCR-transgenic mice was unable to
      reconstitute EAE in the ADAP-deficient animals, indicating that the milder EAE
      was dependent on (a) radio-resistant nonhematopoietic cell population(s). Two
      photon microscopy of lymph node explants revealed that adoptively transferred
      lymphocytes accumulated at lymphatic vessels in the lymph nodes of ADAP-deficient
      mice. Thus, our data identify a T cell-independent mechanism of EAE modulation in
      ADAP-deficient mice. 

PMID- 24101552
TI  - Takotsubo cardiomyopathy following subarachnoid haemorrhage.
AB  - A 67-year-old woman was admitted with aneurysmal subarachnoid haemorrhage and a
      12-lead ECG showed ST segment elevation. Transthoracic echocardiography confirmed
      akinesis of the left ventricular mid-apical segment, with an ejection fraction of
      26%, features characteristic of takotsubo cardiomyopathy. Five days later, we
      identified thrombus in the apex of the left ventricle. Sixteen days after onset,
      the thrombus had disappeared and wall motion improved (ejection fraction 58%)
      without evidence of cardioembolism. Takotsubo cardiomyopathy is a cause of
      cardiac dysfunction after stroke, including SAH. It is characterised by
      transiently depressed contractile function of the left mid and apical ventricle,
      without obstructive coronary artery disease. Clinicians should suspect takotsubo
      cardiomyopathy in patients with subarachnoid haemorrhage who have an ECG
      abnormality. Echocardiography is needed to detect the distinctive regional wall
      motion abnormality. Despite its severity in the acute phase, takotsubo
      cardiomyopathy is self-limiting and its management is conservative. 

PMID- 24101553
TI  - Barriers and facilitators to the implementation of lay health worker programmes
      to improve access to maternal and child health: qualitative evidence synthesis.
AB  - BACKGROUND: Lay health workers (LHWs) perform functions related to healthcare
      delivery, receive some level of training, but have no formal professional or
      paraprofessional certificate or tertiary education degree. They provide care for
      a range of issues, including maternal and child health. For LHW programmes to be
      effective, we need a better understanding of the factors that influence their
      success and sustainability. This review addresses these issues through a
      synthesis of qualitative evidence and was carried out alongside the Cochrane
      review of the effectiveness of LHWs for maternal and child health. OBJECTIVES:
      The overall aim of the review is to explore factors affecting the implementation
      of LHW programmes for maternal and child health. SEARCH METHODS: We searched
      MEDLINE, OvidSP (searched 21 December 2011); MEDLINE Ovid In-Process & Other Non
      Indexed Citations, OvidSP (searched 21 December 2011); CINAHL, EBSCO (searched 21
      December 2011); British Nursing Index and Archive, OvidSP (searched 13 May 2011).
      We searched reference lists of included studies, contacted experts in the field,
      and included studies that were carried out alongside the trials from the LHW
      effectiveness review. SELECTION CRITERIA: Studies that used qualitative methods
      for data collection and analysis and that focused on the experiences and
      attitudes of stakeholders regarding LHW programmes for maternal or child health
      in a primary or community healthcare setting. DATA COLLECTION AND ANALYSIS: We
      identified barriers and facilitators to LHW programme implementation using the
      framework thematic synthesis approach. Two review authors independently assessed
      study quality using a standard tool. We assessed the certainty of the review
      findings using the CerQual approach, an approach that we developed alongside this
      and related qualitative syntheses. We integrated our findings with the outcome
      measures included in the review of LHW programme effectiveness in a logic model.
      Finally, we identified hypotheses for subgroup analyses in future updates of the
      review of effectiveness. MAIN RESULTS: We included 53 studies primarily
      describing the experiences of LHWs, programme recipients, and other health
      workers. LHWs in high income countries mainly offered promotion, counselling and
      support. In low and middle income countries, LHWs offered similar services but
      sometimes also distributed supplements, contraceptives and other products, and
      diagnosed and treated children with common childhood diseases. Some LHWs were
      trained to manage uncomplicated labour and to refer women with pregnancy or
      labour complications.Many of the findings were based on studies from multiple
      settings, but with some methodological limitations. These findings were assessed
      as being of moderate certainty. Some findings were based on one or two studies
      and had some methodological limitations. These were assessed have low
      certainty.Barriers and facilitators were mainly tied to programme acceptability,
      appropriateness and credibility; and health system constraints. Programme
      recipients were generally positive to the programmes, appreciating the LHWs'
      skills and the similarities they saw between themselves and the LHWs. However,
      some recipients were concerned about confidentiality when receiving home visits.
      Others saw LHW services as not relevant or not sufficient, particularly when LHWs
      only offered promotional services. LHWs and recipients emphasised the importance
      of trust, respect, kindness and empathy. However, LHWs sometimes found it
      difficult to manage emotional relationships and boundaries with recipients. Some
      LHWs feared blame if care was not successful. Others felt demotivated when their
      services were not appreciated. Support from health systems and community leaders
      could give LHWs credibility, at least if the health systems and community leaders
      had authority and respect. Active support from family members was also
      important.Health professionals often appreciated the LHWs' contributions in
      reducing their workload and for their communication skills and commitment.
      However, some health professionals thought that LHWs added to their workload and
      feared a loss of authority.LHWs were motivated by factors including altruism,
      social recognition, knowledge gain and career development. Some unsalaried LHWs
      wanted regular payment, while others were concerned that payment might threaten
      their social status or lead recipients to question their motives. Some salaried
      LHWs were dissatisfied with their pay levels. Others were frustrated when payment
      differed across regions or institutions. Some LHWs stated that they had few
      opportunities to voice complaints. LHWs described insufficient, poor quality,
      irrelevant and inflexible training programmes, calling for more training in
      counselling and communication and in topics outside their current role, including
      common health problems and domestic problems. LHWs and supervisors complained
      about supervisors' lack of skills, time and transportation. Some LHWs appreciated
      the opportunity to share experiences with fellow LHWs.In some studies, LHWs were
      traditional birth attendants who had received additional training. Some health
      professionals were concerned that these LHWs were over-confident about their
      ability to manage danger signs. LHWs and recipients pointed to other problems,
      including women's reluctance to be referred after bad experiences with health
      professionals, fear of caesarean sections, lack of transport, and cost. Some LHWs
      were reluctant to refer women on because of poor co-operation with health
      professionals.We organised these findings and the outcome measures included in
      the review of LHW programme effectiveness in a logic model. Here we proposed six
      chains of events where specific programme components lead to specific
      intermediate or long-term outcomes, and where specific moderators positively or
      negatively affect this process. We suggest how future updates of the LHW
      effectiveness review could explore whether the presence of these components
      influences programme success. AUTHORS' CONCLUSIONS: Rather than being seen as a
      lesser trained health worker, LHWs may represent a different and sometimes
      preferred type of health worker. The close relationship between LHWs and
      recipients is a programme strength. However, programme planners must consider how
      to achieve the benefits of closeness while minimizing the potential drawbacks.
      Other important facilitators may include the development of services that
      recipients perceive as relevant; regular and visible support from the health
      system and the community; and appropriate training, supervision and incentives.

PMID- 24101554
TI  - Cross-sensory reference frame transfer in spatial memory: the case of
      proprioceptive learning.
AB  - In three experiments, we investigated whether the information available to visual
      perception prior to encoding the locations of objects in a path through
      proprioception would influence the reference direction from which the spatial
      memory was formed. Participants walked a path whose orientation was misaligned to
      the walls of the enclosing room and to the square sheet that covered the path
      prior to learning (Exp. 1) and, in addition, to the intrinsic structure of a
      layout studied visually prior to walking the path and to the orientation of
      stripes drawn on the floor (Exps. 2 and 3). Despite the availability of prior
      visual information, participants constructed spatial memories that were aligned
      with the canonical axes of the path, as opposed to the reference directions
      primed by visual experience. The results are discussed in the context of previous
      studies documenting transfer of reference frames within and across perceptual
      modalities. 

PMID- 24101555
TI  - Keratinocyte growth factor and thiazolidinediones and linolenic acid
      differentiate characterized mammary fat pad adipose stem cells isolated from
      prepubertal Korean black goat to epithelial and adipogenic lineage.
AB  - The study was conducted to know and investigate the mechanism involved during
      mesenchymal to epithelial transition to unravel questions related to mammary
      gland development in prepubertal Korean black goat. We, therefore, biopsied
      mammary fat pad and isolated adipose cells and characterized with stemness
      factors (CD34, CD13, CD44, CD106, and vimentin) immunologically and through their
      genetic expression. Furthermore, characterized cells were differentiated to
      adipogenic (thiazolidinediones and alpha-linolenic acid) and epithelial
      (keratinocyte growth factor) lineages. Thiazolidinediones/or in combination with
      alpha-linolenic acid demonstrated significant upregulation of adipo-Q, PPAR
      gamma, CEBP-alpha, LPL, and resistin. Adipose stem cells in induction mixture (5
      MUg/ml insulin, 1 MUg/ml hydrocortisone, and 10 ng/ml epidermal growth factor)
      and subsequent treatment with 10 ng/ml keratinocyte growth factor revealed their
      trans-differentiating ability to epithelial lineage. From 2 d onwards, the cells
      under keratinocyte growth factor influenced cells to assume rectangular (2-4 d)
      to cuboidal (8-10 d) shapes. Ayoub-Shklar stain developed brownish-red pigment in
      the transformed cells. Though, expressions of K8 and K18 were noted to be highly
      significant (p < 0.01) but expressions of epithelial membrane antigens and
      epithelial specific antigens were also significant (p < 0.05) compared to 0 d.
      Conclusively, epithelial transformations of mammary adipose stem cells would add
      up knowledge to develop therapeutic regimen to deal with mammary tissue injury
      and diseases.

PMID- 24101556
TI  - Extracellular glutathione promotes migration of hydrogen peroxide-stressed
      cultured chick embryonic skin cells.
AB  - The ability of glutathione to affect melanocyte survival has fostered its use in
      a variety of applications related to epithelial cells. Our study focused on
      fibroblast migration and the effects of oxidative stress. We used scratch assays
      to measure cell migration: fibroblasts were harvested from embryonic chicks,
      grown to confluence in a monolayer, and the layer was scratched to initiate
      migration. Migration rates were measured over 8 h using photomicrographs, and
      vinculin expression as an indicator focal adhesion formation was measured using
      immunofluorescence. Addition of 200 MUM glutathione to the culture media in which
      the cells grew resulted in a significantly increased rate of scratch closure.
      When the scratch assays were performed in the presence of 100 MUM H2O2 (to
      simulate oxidative stress), the cells ceased to migrate. Addition of 200 MUM
      glutathione to the H2O2-treated scratched layers resulted in a restoration of the
      scratch closure capabilities. At the subcellular level, addition of extracellular
      glutathione resulted in a redistribution of vinculin into fewer but larger
      aggregates. In cells at the edge of scratched monolayers that were treated with
      H2O2, vinculin particles were distributed throughout the cell in smaller
      aggregates; addition of glutathione resulted in vinculin aggregates that were
      larger and closer to the edges of the cell, indicating that these cells were more
      migratory. Our results suggest that glutathione promotes fibroblast migration,
      possibly via a mechanism that promotes the formation of focal adhesions.

PMID- 24101560
TI  - The effects of selenium on polyunsaturated fatty acids of Diasporangium
      jonesianum.
AB  - Fungi had become the main resource of polyunsaturated fatty acids, especially
      linoleic acid. The research studied the effects and mechanism of selenium on
      polyunsaturated fatty acids of Diasporangium jonesianum. The results showed that
      selenium could significantly increase the yields of linoleic acid. In contrast,
      the growth and gamma-linolenic acid yield of D. jonesianum was decreased under
      selenium treatments. Delta6-Fatty acid desaturase gene of D. jonesianum was
      investigated in this research. Sequence analysis indicated that this cDNA
      sequence encoded 235 amino acids. The conserved region of Delta6-fatty acid
      desaturase included three conserved histidine-rich domain, hydropathy profile,
      and was rich in disulfide bonds. This study showed that selenium may in
      discriminatively substitute S and incorporate selenium-amino acids into the
      desaturase that the conformation of enzyme active sites was impacted which leaded
      to the inhibition of the convert of linoleic acid to gamma-linolenic acid and the
      over accumulation of linoleic acid. Selenium might enhance the fatty acid
      contents of fungi through influencing the desaturase structure. 

PMID- 24101561
TI  - Development of flow cytometric protocol for nuclear DNA content estimation and
      determination of chromosome number in Pongamia pinnata L., a valuable biodiesel
      plant.
AB  - The potentiality of Pongamia pinnata L. as a sustainable source of feedstock for
      the biodiesel industry is dependent on an extensive knowledge of the genome
      structure of the plant. Flow cytometry, with propidium iodide (PI) as the DNA
      stain, was used to estimate the nuclear DNA content of P. pinnata, with respect
      to Zea mays 'CE-777' as standard. The internal and pseudo-internal
      standardization was followed on account of the inhibitory effect of secondary
      compounds on PI intercalation. The antioxidants (PVP-40 and beta-mercaptoethanol)
      were added to the nuclear isolation buffer for the reduction of inhibitory effect
      of P. pinnata cytosol. Nuclear DNA content estimation was done for P. pinnata
      leaves from different altitudes (37-117 m height from sea level) of Assam. Flow
      cytometry analysis indicated that the nuclear DNA content of P. pinnata is 2.66
      pg with predicted 1C value of 1,300 Mb using Z. mays as standard. Coefficient of
      variation in flow cytometric analysis was within the limit of 5 % indicating that
      the results were reliable. Somatic chromosome numbers were counted from root-tip
      cells and was found to be 2n = 22 corresponding to the diploid level (x = 11). A
      decreasing trend in the nuclear DNA content was observed for the species of
      different altitudes.

PMID- 24101562
TI  - Siderophore production by Bacillus megaterium: effect of growth phase and
      cultural conditions.
AB  - Siderophore production by Bacillus megaterium was detected, in an iron-deficient
      culture medium, during the exponential growth phase, prior to the sporulation, in
      the presence of glucose; these results suggested that the onset of siderophore
      production did not require glucose depletion and was not related with the
      sporulation. The siderophore production by B. megaterium was affected by the
      carbon source used. The growth on glycerol promoted the very high siderophore
      production (1,182 MUmol g(-1) dry weight biomass); the opposite effect was
      observed in the presence of mannose (251 MUmol g(-1) dry weight biomass). The
      growth in the presence of fructose, galactose, glucose, lactose, maltose or
      sucrose, originated similar concentrations of siderophore (546-842 MUmol g(-1)
      dry weight biomass). Aeration had a positive effect on the production of
      siderophore. Incubation of B. megaterium under static conditions delayed and
      reduced the growth and the production of siderophore, compared with the
      incubation in stirred conditions.

PMID- 24101563
TI  - When best evidence is rarer than the disease.

PMID- 24101566
TI  - Book explores challenges in developing cancer drugs: British oncologist discusses
      "random, unpredictable world" of biotechnology.

PMID- 24101567
TI  - Lung cancer patients with an abnormal gene benefit from targeted therapy.

PMID- 24101568
TI  - Tightening tobacco restrictions on teens may impact adult smoking.

PMID- 24101570
TI  - The frequentist implications of optional stopping on Bayesian hypothesis tests.
AB  - Null hypothesis significance testing (NHST) is the most commonly used statistical
      methodology in psychology. The probability of achieving a value as extreme or
      more extreme than the statistic obtained from the data is evaluated, and if it is
      low enough, the null hypothesis is rejected. However, because common experimental
      practice often clashes with the assumptions underlying NHST, these calculated
      probabilities are often incorrect. Most commonly, experimenters use tests that
      assume that sample sizes are fixed in advance of data collection but then use the
      data to determine when to stop; in the limit, experimenters can use data
      monitoring to guarantee that the null hypothesis will be rejected. Bayesian
      hypothesis testing (BHT) provides a solution to these ills because the stopping
      rule used is irrelevant to the calculation of a Bayes factor. In addition, there
      are strong mathematical guarantees on the frequentist properties of BHT that are
      comforting for researchers concerned that stopping rules could influence the
      Bayes factors produced. Here, we show that these guaranteed bounds have limited
      scope and often do not apply in psychological research. Specifically, we
      quantitatively demonstrate the impact of optional stopping on the resulting Bayes
      factors in two common situations: (1) when the truth is a combination of the
      hypotheses, such as in a heterogeneous population, and (2) when a hypothesis is
      composite-taking multiple parameter values-such as the alternative hypothesis in
      a t-test. We found that, for these situations, while the Bayesian interpretation
      remains correct regardless of the stopping rule used, the choice of stopping rule
      can, in some situations, greatly increase the chance of experimenters finding
      evidence in the direction they desire. We suggest ways to control these
      frequentist implications of stopping rules on BHT.

PMID- 24101571
TI  - Aging and the use of interword spaces during reading: evidence from eye
      movements.
AB  - In an eye movement experiment, we assessed the performance of young (18-30 years)
      and older (65 + years) adult readers when sentences contained conventional
      interword spaces, when interword spaces were removed, or when interword spaces
      were replaced by nonlinguistic symbols. The replacement symbol was either a
      closed square ([Symbol: see text]) that provided a salient (low-spatial
      frequency) cue to word boundaries, or an open square (?) that provided a less
      salient cue and included features (vertical and horizontal lines) similar to
      those found in letters. Removing or replacing interword spaces slowed reading
      times and impaired normal eye movement behavior for both age groups. However,
      this disruption was greater for the older readers, particularly when the
      replacement symbol did not provide a salient cue as to word boundaries. Specific
      influences of this manipulation on word identification during reading were
      assessed by examining eye movements for a high- or low-frequency target word in
      each sentence. Standard word frequency effects were obtained for both age groups
      when text was spaced normally, and although the word frequency effect was larger
      when spaces were removed or filled, the increases were similar across age groups.
      Therefore, whereas older adults' normal eye movements were substantially
      disrupted when text lacked conventional interword spaces, the process of lexical
      access associated with the word frequency effect was no more difficult for older
      than for young adults. The indication, therefore, is that although older adults
      struggle from the loss of conventional cues to word boundaries, this is not due
      to additional difficulties in word recognition. 

PMID- 24101572
TI  - Joint response-effect compatibility.
AB  - When performing jointly on a task, human agents are assumed to represent their
      coactor's share of this task, and research in various joint action paradigms has
      focused on representing the coactor's stimulus-response assignments. Here we show
      that the response-effect (R-E) contingencies exploited by a coactor also affect
      performance, and thus might be represented as if they were used by oneself.
      Participants performed an R-E compatibility task, with keypresses producing
      spatially compatible or incompatible action effects. We did not observe any R-E
      compatibility effects when the task was performed in isolation (individual go-no
      go). By contrast, small but reliable R-E compatibility effects emerged when the
      same task was performed in a joint setting. These results indicate that the
      knowledge of a coactor's R-E contingencies can influence whether self-produced
      action effects are used for one's own motor control. 

PMID- 24101573
TI  - Exogenous orienting of crossmodal attention in 3-D space: support for a depth
      aware crossmodal attentional system.
AB  - The aim of the present study was to investigate exogenous crossmodal orienting of
      attention in three-dimensional (3-D) space. Most studies in which the orienting
      of attention has been examined in 3-D space concerned either exogenous intramodal
      or endogenous crossmodal attention. Evidence for exogenous crossmodal orienting
      of attention in depth is lacking. Endogenous and exogenous attention are
      behaviorally different, suggesting that they are two different mechanisms. We
      used the orthogonal spatial-cueing paradigm and presented auditory exogenous cues
      at one of four possible locations in near or far space before the onset of a
      visual target. Cues could be presented at the same (valid) or at a different
      (invalid) depth from the target (radial validity), and on the same (valid) or on
      a different (invalid) side (horizontal validity), whereas we blocked the depth at
      which visual targets were presented. Next to an overall validity effect (valid
      RTs < invalid RTs) in horizontal space, we observed an interaction between the
      horizontal and radial validity of the cue: The horizontal validity effect was
      present only when the cue and the target were presented at the same depth. No
      horizontal validity effect was observed when the cue and the target were
      presented at different depths. These results suggest that exogenous crossmodal
      attention is "depth-aware," and they are discussed in the context of the
      supramodal hypothesis of attention. 

PMID- 24101574
TI  - Many hurdles for the translation of species preservation research : comment on
      "ethics of species research and preservation" by Rob Irvine.

PMID- 24101575
TI  - Identification of poor performance in a national medical workforce over 11 years:
      an observational study.
AB  - BACKGROUND: Poorly performing doctors are a source of harm but do not commonly
      feature in discussions of patient safety. Few countries have national mechanisms
      to deal with these doctors; most opt for suspension and/or exclusion from
      clinical practice. This study reports on the 11-year experience of dealing with
      concerns about doctors' performance in the UK National Health Service (NHS). The
      aim of this study was to describe the frequency with which doctors were referred
      due to performance-related concerns, examine demographic and specialty
      differences, and identify the nature of the concerns prompting referral. METHODS:
      This observational study uses data collected by the National Clinical Assessment
      Service for each referral (n=6179 doctors) over an 11-year period (April 2001
      March 2012) in England to examine the rate at which concerns about doctors'
      performance occur, understand differences in rates between practitioner groups,
      and changes over time. FINDINGS: The annual referral rate was five per 1000
      doctors (95% CI 4.6 to 5.4). Doctors whose first medical qualification was gained
      outside the UK were more than twice as likely to be referred as UK-qualified
      doctors; male doctors were more than twice as likely to be referred as women
      doctors; and doctors in the late stages of their career were nearly six times as
      likely to be referred as early career doctors. DISCUSSION: The UK holds a
      consistently collected national dataset on performance concerns about doctors.
      This allows risk groups to be identified so that preventive action and early
      intervention can be targeted most effectively to reduce harm to patients. A
      feature of past handling of poor clinical performance has been late presentation
      and a lack of thematic study of causation.

PMID- 24101576
TI  - Wi-Fi (2.45 GHz)- and mobile phone (900 and 1800 MHz)-induced risks on oxidative
      stress and elements in kidney and testis of rats during pregnancy and the
      development of offspring.
AB  - The present study was designed to determine the effects of both Wi-Fi (2.45 GHz)-
      and mobile phone (900 and 1800 MHz)-induced electromagnetic radiation (EMR) on
      oxidative stress and trace element levels in the kidney and testis of growing
      rats from pregnancy to 6 weeks of age. Thirty-two rats and their 96 newborn
      offspring were equally divided into four different groups, namely, control, 2.45
      GHz, 900 MHz, and 1800 MHz groups. The 2.45 GHz, 900 MHz, and 1,800 MHz groups
      were exposed to EMR for 60 min/day during pregnancy and growth. During the
      fourth, fifth, and sixth weeks of the experiment, kidney and testis samples were
      taken from decapitated rats. Results from the fourth week showed that the level
      of lipid peroxidation in the kidney and testis and the copper, zinc, reduced
      glutathione (GSH), glutathione peroxidase (GSH-Px), and total antioxidant status
      (TAS) values in the kidney decreased in the EMR groups, while iron concentrations
      in the kidney as well as vitamin A and vitamin E concentrations in the testis
      increased in the EMR groups. Results for fifth-week samples showed that iron,
      vitamin A, and beta-carotene concentrations in the kidney increased in the EMR
      groups, while the GSH and TAS levels decreased. The sixth week results showed
      that iron concentrations in the kidney and the extent of lipid peroxidation in
      the kidney and testis increased in the EMR groups, while copper, TAS, and GSH
      concentrations decreased. There were no statistically significant differences in
      kidney chromium, magnesium, and manganese concentrations among the four groups.
      In conclusion, Wi-Fi- and mobile phone-induced EMR caused oxidative damage by
      increasing the extent of lipid peroxidation and the iron level, while decreasing
      total antioxidant status, copper, and GSH values. Wi-Fi- and mobile phone-induced
      EMR may cause precocious puberty and oxidative kidney and testis injury in
      growing rats.

PMID- 24101578
TI  - Introduction to this issue of Perspectives on Medical Education.

PMID- 24101577
TI  - Breast cancer treatment across health care systems: linking electronic medical
      records and state registry data to enable outcomes research.
AB  - BACKGROUND: Understanding of cancer outcomes is limited by data fragmentation. In
      the current study, the authors analyzed the information yielded by integrating
      breast cancer data from 3 sources: electronic medical records (EMRs) from 2
      health care systems and the state registry. METHODS: Diagnostic test and
      treatment data were extracted from the EMRs of all patients with breast cancer
      treated between 2000 and 2010 in 2 independent California institutions: a
      community-based practice (Palo Alto Medical Foundation; "Community") and an
      academic medical center (Stanford University; "University"). The authors
      incorporated records from the population-based California Cancer Registry and
      then linked EMR-California Cancer Registry data sets of Community and University
      patients. RESULTS: The authors initially identified 8210 University patients and
      5770 Community patients; linked data sets revealed a 16% patient overlap,
      yielding 12,109 unique patients. The percentage of all Community patients, but
      not University patients, treated at both institutions increased with worsening
      cancer prognostic factors. Before linking the data sets, Community patients
      appeared to receive less intervention than University patients (mastectomy: 37.6%
      vs 43.2%; chemotherapy: 35% vs 41.7%; magnetic resonance imaging: 10% vs 29.3%;
      and genetic testing: 2.5% vs 9.2%). Linked Community and University data sets
      revealed that patients treated at both institutions received substantially more
      interventions (mastectomy: 55.8%; chemotherapy: 47.2%; magnetic resonance
      imaging: 38.9%; and genetic testing: 10.9% [P < .001 for each 3-way institutional
      comparison]). CONCLUSIONS: Data linkage identified 16% of patients who were
      treated in 2 health care systems and who, despite comparable prognostic factors,
      received far more intensive treatment than others. By integrating complementary
      data from EMRs and population-based registries, a more comprehensive
      understanding of breast cancer care and factors that drive treatment use was
      obtained.

PMID- 24101579
TI  - Tuning research competences for Bologna three cycles in medicine: report of a
      MEDINE2 European consensus survey.
AB  - Medical curricula, like healthcare systems and medical practice, have a strong
      cultural component and vary considerably between countries. Increasing mobility
      of medical graduates, and increasing pressure to ensure they are all fit for
      practice, have highlighted an urgent need to establish common ground in learning
      outcomes at all stages of training. A research-based approach, developed by the
      Tuning project, was used previously by the MEDINE Thematic Network to gain
      consensus on core learning outcomes/competences for primary medical degrees (
      www.tuning-medicine.com ), but no consensus was reached for learning outcomes
      relating to research. As part of MEDINE2, a focussed Tuning project was
      undertaken to explore opinions on more detailed core learning outcomes in
      research for all three Bologna cycles (Bachelor, Master, and Doctor). Responses
      from 417 stakeholders, representing 29 European and 13 non-European countries,
      revealed a relatively high degree of consensus. The findings strongly suggest
      that these stakeholders think that learning outcomes related both to 'using
      research' and 'doing research' should be core components of medical curricula in
      Europe. The challenge now, however, is to promote further local and international
      discussion on these issues, and to find ways of achieving these competences
      within the context of already crowded medical curricula. 

PMID- 24101580
TI  - Evidence-based practice for individuals or groups: let's make a difference.
AB  - The aim of applying science into practice is to deliver high-quality health care.
      Thinking about teaching the necessary accompanying skills, a distinction can be
      made between using evidence for individual patient care and using scientific
      knowledge for the development of protocols or guidelines for groups of patients
      or professionals. In this paper, these two ways of applying science into practice
      are being considered. We plea for explicating the differences between the
      individual patient and a group of patients or professionals when applying
      scientific knowledge in the decision-making process. The acknowledgment of these
      differences facilitates the teaching of the accompanying competences and
      different CanMEDS roles. 

PMID- 24101581
TI  - Learning of veterinary professionals in communities: a thesis report.
AB  - Veterinary professionals can improve on how they continue learning through
      critically reflective work behaviour in communities. In this way participation in
      communities might support the transition to evidence-based practice. 

PMID- 24101582
TI  - Cardiorenal syndrome: introduction.

PMID- 24101583
TI  - Heterogeneous versus homogeneous copper(II) catalysis in enantioselective
      conjugate-addition reactions of boron in water.
AB  - We have developed Cu(II)-catalyzed enantioselective conjugate-addition reactions
      of boron to alpha,beta-unsaturated carbonyl compounds and alpha,beta,gamma,delta
      unsaturated carbonyl compounds in water. In contrast to the previously reported
      Cu(I) catalysis that required organic solvents, chiral Cu(II) catalysis was found
      to proceed efficiently in water. Three catalyst systems have been exploited: cat.
      1: Cu(OH)2 with chiral ligand L1; cat. 2: Cu(OH)2 and acetic acid with ligand L1;
      and cat. 3: Cu(OAc)2 with ligand L1. Whereas cat. 1 is a heterogeneous system,
      cat. 2 and cat. 3 are homogeneous systems. We tested 27 alpha,beta-unsaturated
      carbonyl compounds and an alpha,beta-unsaturated nitrile compound, including
      acyclic and cyclic alpha,beta-unsaturated ketones, acyclic and cyclic beta,beta
      disubstituted enones, acyclic and cyclic alpha,beta-unsaturated esters (including
      their beta,beta-disubstituted forms), and acyclic alpha,beta-unsaturated amides
      (including their beta,beta-disubstituted forms). We found that cat. 2 and cat. 3
      showed high yields and enantioselectivities for almost all substrates. Notably,
      no catalysts that can tolerate all of these substrates with high yields and high
      enantioselectivities have been reported for the conjugate addition of boron.
      Heterogeneous cat. 1 also gave high yields and enantioselectivities with some
      substrates and also gave the highest TOF (43,200 h(-1) ) for an asymmetric
      conjugate-addition reaction of boron. In addition, the catalyst systems were also
      applicable to the conjugate addition of boron to alpha,beta,gamma,delta
      unsaturated carbonyl compounds, although such reactions have previously been very
      limited in the literature, even in organic solvents. 1,4-Addition products were
      obtained in high yields and enantioselectivities in the reactions of acyclic
      alpha,beta,gamma,delta-unsaturated carbonyl compounds with diboron 2 by using
      cat. 1, cat. 2, or cat. 3. On the other hand, in the reactions of cyclic
      alpha,beta,gamma,delta-unsaturated carbonyl compounds with compound 2, whereas
      1,4-addition products were exclusively obtained by using cat. 2 or cat. 3, 1,6
      addition products were exclusively produced by using cat. 1. Similar unique
      reactivities and selectivities were also shown in the reactions of cyclic
      trienones. Finally, the reaction mechanisms of these unique conjugate-addition
      reactions in water were investigated and we propose stereochemical models that
      are supported by X-ray crystallography and MS (ESI) analysis. Although the role
      of water has not been completely revealed, water is expected to be effective in
      the activation of a borylcopper(II) intermediate and a protonation event
      subsequent to the nucleophilic addition step, thereby leading to overwhelmingly
      high catalytic turnover.

PMID- 24101585
TI  - Ultrastructure of spermatogenesis in Spix's yellow-toothed cavy (Galea spixii).
AB  - This was a pioneer study of the spermatogenic process from the onset of puberty
      in Spix's yellow-toothed cavies (SYC, Galea spixii) bred in captivity. The study
      aimed to characterize fine structure of spermatogenesis. Twelve testes from
      pubertal and post-pubertal SYC males were studied using transmission electron
      microscopy. Spermatogenesis can be divided into three phases: proliferation,
      meiosis, and spermiogenesis. In proliferation phase, three types of spermatogonia
      were identified and characterized as A(dark), A(pale), and B. In the second
      phase, spermatocytes (2n) undergo meiotic divisions that generate spermatids (n);
      the process begins in spermatocytes in the preleptotene stage when they increase
      their nuclear size, differentiating into spermatocytes in the leptotene stage
      when cell division is initiated. In addition, we found chromatin condensation,
      and formation of a structure composed of proteins that formed a central shaft and
      two lateral bars associated with pairing of homologous chromosomes. During
      spermiogenesis, the following main events occurred: condensation of nuclear
      chromatin, formation of acrosome with perfuratorium, elimination of residual
      cytoplasm, and development of the flagellum. The sperm head is different from
      that of other rodents. The endoplasmic reticulum and the Golgi complex are the
      two main organelles demonstrated during this process. These organelles
      collaborate through synthesis of proteins and hormones for the development of
      germ cells during spermatogenesis in SYC.

PMID- 24101584
TI  - Chronic exendin-4 treatment prevents the development of cancer cachexia symptoms
      in male rats bearing the Yoshida sarcoma.
AB  - Cancer cachexia is the syndrome of weight loss, loss of appetite, and wasting of
      skeletal muscle and adipose tissue experienced by many individuals with cancer.
      Currently, few effective treatment and prevention strategies are available for
      these patients, due in part to a poor understanding of the mechanisms
      contributing to cachexia. Insulin resistance has been associated with cancer
      cachexia in epidemiological, human, and animal research. The present experiment
      was designed to examine the ability of Exendin-4, a GLP-1 agonist and insulin
      sensitizing agent, to prevent the development of cachexia symptoms in male
      Sprague Dawley rats bearing the Yoshida sarcoma. Following tumor implantation or
      sham surgery, rats were treated daily with saline or Exendin-4 (3 MUg/kg body
      weight/day) and were monitored for tumor growth and cachexia symptoms for 21-23
      days. As a result of large variability in treatment effects, data were analyzed
      separately for animals with large and small tumors. Exendin-4 treatment reduced
      tumor growth and prevented the development of cancer cachexia symptoms in animals
      with small, but not large, tumors. In addition, insulin levels were preserved in
      Exendin-4-treated tumor-bearing animals. The results of this experiment
      demonstrate a novel preventative therapy for cancer cachexia and a novel use of
      Exendin-4. Further research is necessary to determine the mechanisms through
      which Exendin-4 exerts these potent effects. 

PMID- 24101587
TI  - UK medical school over-assessment: a simple solution.

PMID- 24101586
TI  - Lysosomal network proteins as potential novel CSF biomarkers for Alzheimer's
      disease.
AB  - The success of future intervention strategies for Alzheimer's disease (AD) will
      likely rely on the development of treatments starting early in the disease
      course, before irreversible brain damage occurs. The pre-symptomatic stage of AD
      occurs at least one decade before the clinical onset, highlighting the need for
      validated biomarkers that reflect this early period. Reliable biomarkers for AD
      are also needed in research and clinics for diagnosis, patient stratification,
      clinical trials, monitoring of disease progression and the development of new
      treatments. Changes in the lysosomal network, i.e., the endosomal, lysosomal and
      autophagy systems, are among the first alterations observed in an AD brain. In
      this study, we performed a targeted search for lysosomal network proteins in
      human cerebrospinal fluid (CSF). Thirty-four proteins were investigated, and six
      of them, early endosomal antigen 1 (EEA1), lysosomal-associated membrane proteins
      1 and 2 (LAMP-1, LAMP-2), microtubule-associated protein 1 light chain 3 (LC3),
      Rab3 and Rab7, were significantly increased in the CSF from AD patients compared
      with neurological controls. These results were confirmed in a validation cohort
      of CSF samples, and patients with no neurochemical evidence of AD, apart from
      increased total-tau, were found to have EEA1 levels corresponding to the
      increased total-tau levels. These findings indicate that increased levels of LAMP
      1, LAMP-2, LC3, Rab3 and Rab7 in the CSF might be specific for AD, and increased
      EEA1 levels may be a sign of general neurodegeneration. These six lysosomal
      network proteins are potential AD biomarkers and may be used to investigate
      lysosomal involvement in AD pathogenesis. 

PMID- 24101589
TI  - Iron- and bismuth-catalyzed asymmetric Mukaiyama aldol reactions in aqueous
      media.
AB  - We have developed asymmetric Mukaiyama aldol reactions of silicon enolates with
      aldehydes catalyzed by chiral Fe(II) and Bi(III) complexes. Although previous
      reactions often required relatively harsh conditions, such as strictly anhydrous
      conditions, very low temperatures (-78  degrees C), etc., the reactions reported
      herein proceeded in the presence of water at 0  degrees C. To find appropriate
      chiral water-compatible Lewis acids for the Mukaiyama aldol reaction, many Lewis
      acids were screened in combination with chiral bipyridine L1, which had
      previously been found to be a suitable chiral ligand in aqueous media. Three
      types of chiral catalysts that consisted of a Fe(II) or Bi(III) metal salt, a
      chiral ligand (L1), and an additive have been discovered and a wide variety of
      substrates (silicon enolates and aldehydes) reacted to afford the desired aldol
      products in high yields with high diastereo- and enantioselectivities through an
      appropriate selection of one of the three catalytic systems. Mechanistic studies
      elucidated the coordination environments around the Fe(II) and Bi(III) centers
      and the effect of additives on the chiral catalysis. Notably, both Bronsted acids
      and bases worked as efficient additives in the Fe(II) -catalyzed reactions. The
      assumed catalytic cycle and transition states indicated important roles of water
      in these efficient asymmetric Mukaiyama aldol reactions in aqueous media with the
      broadly applicable and versatile catalytic systems.

PMID- 24101588
TI  - Human LINE-1 restriction by APOBEC3C is deaminase independent and mediated by an
      ORF1p interaction that affects LINE reverse transcriptase activity.
AB  - LINE-1 (L1) retrotransposons are mobile genetic elements whose extensive
      proliferation resulted in the generation of ~ 34% of the human genome. They have
      been shown to be a cause of single-gene diseases. Moreover, L1-encoded
      endonuclease can elicit double-strand breaks that may lead to genomic
      instability. Mammalian cells adopted strategies restricting mobility and
      deleterious consequences of uncontrolled retrotransposition. The human APOBEC3
      protein family of polynucleotide cytidine deaminases contributes to intracellular
      defense against retroelements. APOBEC3 members inhibit L1 retrotransposition by
      35-99%. However, genomic L1 retrotransposition events that occurred in the
      presence of L1-restricting APOBEC3 proteins are devoid of detectable G-to-A
      hypermutations, suggesting one or multiple deaminase-independent L1 restricting
      mechanisms. We set out to uncover the mechanism of APOBEC3C (A3C)-mediated L1
      inhibition and found that it is deaminase independent, requires an intact
      dimerization site and the RNA-binding pocket mutation R122A abolishes L1
      restriction by A3C. Density gradient centrifugation of L1 ribonucleoprotein
      particles, subcellular co-localization of L1-ORF1p and A3C and co
      immunoprecipitation experiments indicate that an RNA-dependent physical
      interaction between L1 ORF1p and A3C dimers is essential for L1 restriction.
      Furthermore, we demonstrate that the amount of L1 complementary DNA synthesized
      by L1 reverse transcriptase is reduced by ~ 50% if overexpressed A3C is present.

PMID- 24101590
TI  - Enamel defects on the maxillary premolars in patients with cleft lip and/or
      palate: a retrospective case-control study.
AB  - AIM: The purpose of this study was to investigate the presence of developmental
      defects of enamel on maxillary premolars in patients with cleft lip and/or
      palate. In addition, the relationship with the surgical technique of soft palate
      closure was studied. Such a relationship could be suspected since formation of
      enamel occurs around the same time period as soft palate closure. MATERIALS AND
      METHODS: The study consisted of three groups. Patients from the first group (n =
      123) were recruited from the Cleft Lip and Palate Team of the University
      Hospitals Leuven (CLPT-UHL). The second group (n = 81) consisted of patients
      consulting the Cleft Lip and Palate Team of the Radboud University Medical Centre
      Nijmegen (CLPT-UMCN). Healthy non-cleft lip and/or palate patients (n = 100)
      recruited from a private orthodontic practice were enrolled in group 3. All
      maxillary premolars were examined. RESULTS: Out of the total sample, 43 patients
      showed developmental defects on one or more premolars. All defects occurred in
      patients of group 1 who received surgical closure by the CLPT-UHL. None of the
      patients from group 2 and 3 showed defects. CONCLUSIONS: It can be suggested that
      the surgical technique, used by the CLPT-UHL for soft palate closure, causes
      these defects. It is postulated that the technique used by the CLPT-UHL leads to
      interference with the blood supply of the developing premolar at a critical stage
      of tooth enamel development. More research is needed to confirm these findings.

PMID- 24101591
TI  - Optimal fit of chairside-fabricated distal shoe space maintainer.
AB  - BACKGROUND: Premature loss of a primary second molar may lead to space loss in
      the dental arch. This space loss tends to be more severe in unfavourable
      malocclusions. The distal shoe space maintainer (DSSM) may be beneficial in
      controlling the path of eruption of an unerupted permanent first molar from the
      primary into the early mixed dentition. TECHNIQUE: This article describes the
      technique for achieving optimal fit of a chairside-fabricated band and DSSM in a
      single visit by contouring the distal shoe blade, and by extending it to the
      mesial surface of the permanent first molar. FOLLOW-UP CARE: Upon the eruption of
      the permanent first molar DSSM may be modified to a reverse band-and-loop, or
      replaced by a lingual holding arch.

PMID- 24101593
TI  - Medicaid roadblocks.

PMID- 24101594
TI  - One year to go.

PMID- 24101592
TI  - Serum cystatin C and indices of lung function in elderly Chinese men with chronic
      obstructive pulmonary disease.
AB  - OBJECTIVE: The aim of this cross-sectional case-control study was to determine
      the relationship between serum cystatin C (sCysC) levels and lung function in
      elderly male patients with chronic obstructive pulmonary disease (COPD). METHODS:
      This study included 251 Chinese men (age >= 65 years) who were divided into COPD
      (n = 129) and non-COPD (n = 122) groups. Participants underwent lung function and
      laboratory testing, including measurement of sCysC levels. Relationships between
      sCysC concentration and indices of lung function were assessed by multiple
      regression analysis. RESULTS: Participants in the COPD group displayed higher
      sCysC concentrations (P = 0.041) and lower lung function (P < 0.001) compared to
      participants in the non-COPD group. Multiple linear regression analyses revealed
      that the reciprocal of the sCysC concentration (1/sCysC) was positively
      associated with the predicted forced expiratory volume in 1 s in all subjects
      (beta = 0.156, P = 0.009). The findings indicate that high sCysC levels were
      directly associated with decreased lung function in elderly Chinese men with
      COPD. CONCLUSIONS: High sCysC concentration may be a potential indicator of
      impaired lung function, and its application may improve the diagnosis and
      assessment of COPD severity in elderly male patients.

PMID- 24101595
TI  - PHI, BAs, and NPPs.

PMID- 24101596
TI  - Under new management.

PMID- 24101597
TI  - Good advice.

PMID- 24101598
TI  - Texas first.

PMID- 24101599
TI  - Mid-stage intervention achieves similar efficacy as conventional early-stage
      treatment using gene therapy in a pre-clinical model of retinitis pigmentosa.
AB  - Deficiencies in rod-specific cyclic guanosine monophosphate (cGMP)
      phosphodiesterase-6 (PDE6) are the third most common cause of autosomal recessive
      retinitis pigmentosa (RP). Previously, viral gene therapy approaches on pre
      clinical models with mutations in PDE6 have demonstrated that the photoreceptor
      cell survival and visual function can be rescued when the gene therapy virus is
      delivered into the subretinal space before the onset of disease. However, no
      studies have currently been published that analyze rescue effects after disease
      onset, a time when human RP patients are diagnosed by a clinician and would
      receive the treatment. We utilized the AAV2/8(Y733F)-Rho-Pde6alpha gene therapy
      virus and injected it into a pre-clinical model of RP with a mutation within the
      alpha subunit of PDE6: Pde6alpha(D670G). These mice were previously shown to have
      long-term photoreceptor cell rescue when this gene therapy virus was delivered
      before the onset of disease. Now, we have determined that subretinal transduction
      of this rod-specific transgene at post-natal day (P) 21, when approximately half
      of the photoreceptor cells have undergone degeneration, is more efficient in
      rescuing cone than rod photoreceptor function long term. Therefore, AAV2/8(Y733F)
      Rho-Pde6alpha is an effective gene therapy treatment that can be utilized in the
      clinical setting, in human patients who have lost portions of their peripheral
      visual field and are in the mid-stage of disease when they first present to an
      eye-care professional.

PMID- 24101600
TI  - Differential, dominant activation and inhibition of Notch signalling and APP
      cleavage by truncations of PSEN1 in human disease.
AB  - PRESENILIN1 (PSEN1) is the major locus for mutations causing familial Alzheimer's
      disease (FAD) and is also mutated in Pick disease of brain, familial acne inversa
      and dilated cardiomyopathy. It is a critical facilitator of Notch signalling and
      many other signalling pathways and protein cleavage events including production
      of the Amyloidbeta (Abeta) peptide from the AMYLOID BETA A4 PRECURSOR PROTEIN
      (APP). We previously reported that interference with splicing of transcripts of
      the zebrafish orthologue of PSEN1 creates dominant negative effects on Notch
      signalling. Here, we extend this work to show that various truncations of human
      PSEN1 (or zebrafish Psen1) protein have starkly differential effects on Notch
      signalling and cleavage of zebrafish Appa (a paralogue of human APP). Different
      truncations can suppress or stimulate Notch signalling but not Appa cleavage and
      vice versa. The G183V mutation possibly causing Pick disease causes production of
      aberrant transcripts truncating the open reading frame after exon 5 sequence. We
      show that the truncated protein potentially translated from these transcripts
      avidly incorporates into very stable Psen1-dependent higher molecular weight
      complexes and suppresses cleavage of Appa but not Notch signalling. In contrast,
      the truncated protein potentially produced by the P242LfsX11 acne inversa
      mutation has no effect on Appa cleavage but, unexpectedly, enhances Notch
      signalling. Our results suggest novel hypotheses for the pathological mechanisms
      underlying these diseases and illustrate the importance of investigating the
      function of dominant mutations at physiologically relevant expression levels and
      in the normally heterozygous state in which they cause human disease rather than
      in isolation from healthy alleles. 

PMID- 24101602
TI  - Altered CpG methylation in sporadic Alzheimer's disease is associated with APP
      and MAPT dysregulation.
AB  - The hallmark of Alzheimer's disease (AD) pathology is an accumulation of amyloid
      beta (Abeta) and phosphorylated tau, which are encoded by the amyloid precursor
      protein (APP) and microtubule-associated protein tau (MAPT) genes, respectively.
      Less than 5% of all AD cases are familial in nature, i.e. caused by mutations in
      APP, PSEN1 or PSEN2. Almost all mutations found in them are related to an
      overproduction of Abeta1-42, which is prone to aggregation. While these genes are
      mutation free, their function, or those of related genes, could be compromised in
      sporadic AD as well. In this study, pyrosequencing analysis of post-mortem brains
      revealed aberrant CpG methylation in APP, MAPT and GSK3B genes of the AD brain.
      These changes were further evaluated by a newly developed in vitro-specific DNA
      methylation system, which in turn highlighted an enhanced expression of APP and
      MAPT. Cell nucleus sorting of post-mortem brains revealed that the methylation
      changes of APP and MAPT occurred in both neuronal and non-neuronal cells, whereas
      GSK3B was abnormally methylated in non-neuronal cells. Further analysis revealed
      an association between abnormal APP CpG methylation and apolipoprotein E epsilon4
      allele (APOE epsilon4)-negative cases. The presence of a small number of highly
      methylated neurons among normal neurons contribute to the methylation difference
      in APP and MAPT CpGs, thus abnormally methylated cells could compromise the
      neural circuit and/or serve as 'seed cells' for abnormal protein propagation. Our
      results provide a link between familial AD genes and sporadic neuropathology,
      thus emphasizing an epigenetic pathomechanism for sporadic AD. 

PMID- 24101601
TI  - Rapamycin drives selection against a pathogenic heteroplasmic mitochondrial DNA
      mutation.
AB  - Mitochondrial DNA (mtDNA) mutations cause a variety of mitochondrial disorders
      for which effective treatments are lacking. Emerging data indicate that selective
      mitochondrial degradation through autophagy (mitophagy) plays a critical role in
      mitochondrial quality control. Inhibition of mammalian target of rapamycin (mTOR)
      kinase activity can activate mitophagy. To test the hypothesis that enhancing
      mitophagy would drive selection against dysfunctional mitochondria harboring
      higher levels of mutations, thereby decreasing mutation levels over time, we
      examined the impact of rapamycin on mutation levels in a human cytoplasmic hybrid
      (cybrid) cell line expressing a heteroplasmic mtDNA G11778A mutation, the most
      common cause of Leber's hereditary optic neuropathy. Inhibition of mTORC1/S6
      kinase signaling by rapamycin induced colocalization of mitochondria with
      autophagosomes, and resulted in a striking progressive decrease in levels of the
      G11778A mutation and partial restoration of ATP levels. Rapamycin-induced
      upregulation of mitophagy was confirmed by electron microscopic evidence of
      increased autophagic vacuoles containing mitochondria-like organelles. The
      decreased mutational burden was not due to rapamycin-induced cell death or mtDNA
      depletion, as there was no significant difference in cytotoxicity/apoptosis or
      mtDNA copy number between rapamycin and vehicle-treated cells. These data
      demonstrate the potential for pharmacological inhibition of mTOR kinase activity
      to activate mitophagy as a strategy to drive selection against a heteroplasmic
      mtDNA G11778A mutation and raise the exciting possibility that rapamycin may have
      therapeutic potential for the treatment of mitochondrial disorders associated
      with heteroplasmic mtDNA mutations, although further studies are needed to
      determine if a similar strategy will be effective for other mutations and other
      cell types. 

PMID- 24101603
TI  - Endoscopic ultrasound-guided angiotherapy of a large bleeding gastrointestinal
      stromal tumor.

PMID- 24101604
TI  - Diagnosing ectopic pregnancy and current concepts in the management of pregnancy
      of unknown location.
AB  - BACKGROUND: A diagnosis of ectopic pregnancy (EP) is primarily achieved using
      transvaginal ultrasonography (TVS). Pregnancy of unknown location (PUL) is the
      term used to categorize a pregnancy in a woman with a positive pregnancy test
      when no pregnancy has been visualized using TVS. This review appraises current
      tools for the diagnosis of EP, describes the diagnostic criteria for non-tubal EP
      and reviews the literature on the clinical management of PUL. METHODS: We
      performed a targeted search using the PubMed database. All articles published in
      the English language from January 1984 to March 2013 were screened for
      eligibility. RESULTS: Using TVS to diagnose EP is highly sensitive (87-99%) and
      specific (94-99.9%). Variations exist in the criteria used for ultrasound
      diagnosis. Studies report that between 5 and 42% of women seen for ultrasound
      assessment with a positive pregnancy test have a PUL. For PUL, measurements of
      serum human chorionic gonadotrophin (hCG) and progesterone are used to predict
      pregnancy viability and therefore give an indication of the risk of an EP. Only 6
      20% of PUL are subsequently diagnosed with EP. Non-tubal EPs are relatively
      uncommon, difficult to diagnose and result in disproportionate morbidity and
      mortality. CONCLUSIONS: Access to expertise and equipment for high-quality TVS
      means the majority of women with EP in developed countries can be diagnosed
      rapidly and accurately. Identifying PUL, which are low risk and therefore
      requiring less follow-up, finding better serum markers for EP and safely
      identifying women who do not require intervention for EP are the current
      diagnostic challenges.

PMID- 24101605
TI  - Regulate e-cigarettes as drug-delivery devices.

PMID- 24101608
TI  - HIV infections and AIDS-related deaths falling globally.

PMID- 24101609
TI  - Gender dysphoria in a 39-year-old man.

PMID- 24101610
TI  - US becoming more accepting of medical marijuana.

PMID- 24101613
TI  - Canada's first kids-only ER at a general hospital.

PMID- 24101612
TI  - Prevalence of and factors associated with head impact during falls in older
      adults in long-term care.
AB  - BACKGROUND: Falls cause more than 60% of head injuries in older adults. Lack of
      objective evidence on the circumstances of these events is a barrier to
      prevention. We analyzed video footage to determine the frequency of and risk
      factors for head impact during falls in older adults in 2 long-term care
      facilities. METHODS: Over 39 months, we captured on video 227 falls involving 133
      residents. We used a validated questionnaire to analyze the mechanisms of each
      fall. We then examined whether the probability for head impact was associated
      with upper-limb protective responses (hand impact) and fall direction. RESULTS:
      Head impact occurred in 37% of falls, usually onto a vinyl or linoleum floor.
      Hand impact occurred in 74% of falls but had no significant effect on the
      probability of head impact (p = 0.3). An increased probability of head impact was
      associated with a forward initial fall direction, compared with backward falls
      (odds ratio [OR] 2.7, 95% confidence interval [CI] 1.3-5.9) or sideways falls (OR
      2.8, 95% CI 1.2-6.3). In 36% of sideways falls, residents rotated to land
      backwards, which reduced the probability of head impact (OR 0.2, 95% CI 0.04
      0.8). INTERPRETATION: Head impact was common in observed falls in older adults
      living in long-term care facilities, particularly in forward falls. Backward
      rotation during descent appeared to be protective, but hand impact was not.
      Attention to upper-limb strength and teaching rotational falling techniques (as
      in martial arts training) may reduce fall-related head injuries in older adults.

PMID- 24101614
TI  - Synthetic cannabinoids.

PMID- 24101615
TI  - Health problems abundant in marginalized housing.

PMID- 24101617
TI  - Shutdown hits health services, but Obamacare steams on.

PMID- 24101616
TI  - Managing newly diagnosed thyroid cancer.

PMID- 24101618
TI  - Provinces call for improved senior care.

PMID- 24101619
TI  - Tool use as adaptation.
AB  - Tool use is a vital component of the human behavioural repertoire. The benefits
      of tool use have often been assumed to be self-evident: by extending control over
      our environment, we have increased energetic returns and buffered ourselves from
      potentially harmful influences. In recent decades, however, the study of tool use
      in both humans and non-human animals has expanded the way we think about the role
      of tools in the natural world. This Theme Issue is aimed at bringing together
      this developing body of knowledge, gathered across multiple species and from
      multiple research perspectives, to chart the wider evolutionary context of this
      phylogenetically rare behaviour. 

PMID- 24101620
TI  - The development of tool manufacture in humans: what helps young children make
      innovative tools?
AB  - We know that even young children are proficient tool users, but until recently,
      little was known about how they make tools. Here, we will explore the concepts
      underlying tool making, and the kinds of information and putative cognitive
      abilities required for children to manufacture novel tools. We will review the
      evidence for novel tool manufacture from the comparative literature and present a
      growing body of data from children suggesting that innovation of the solution to
      a problem by making a tool is a much more challenging task than previously
      thought. Children's difficulty with these kinds of tasks does not seem to be
      explained by perseveration with unmodified tools, difficulty with switching to
      alternative strategies, task pragmatics or issues with permission. Rather, making
      novel tools (without having seen an example of the required tool within the
      context of the task) appears to be hard, because it is an example of an 'ill
      structured problem'. In this type of ill-structured problem, the starting
      conditions and end goal are known, but the transformations and/or actions
      required to get from one to the other are not specified. We will discuss the
      implications of these findings for understanding the development of problem
      solving in humans and other animals.

PMID- 24101621
TI  - The fourth dimension of tool use: temporally enduring artefacts aid primates
      learning to use tools.
AB  - All investigated cases of habitual tool use in wild chimpanzees and capuchin
      monkeys include youngsters encountering durable artefacts, most often in a
      supportive social context. We propose that enduring artefacts associated with
      tool use, such as previously used tools, partly processed food items and residual
      material from previous activity, aid non-human primates to learn to use tools,
      and to develop expertise in their use, thus contributing to traditional
      technologies in non-humans. Therefore, social contributions to tool use can be
      considered as situated in the three dimensions of Euclidean space, and in the
      fourth dimension of time. This notion expands the contribution of social context
      to learning a skill beyond the immediate presence of a model nearby. We provide
      examples supporting this hypothesis from wild bearded capuchin monkeys and
      chimpanzees, and suggest avenues for future research. 

PMID- 24101622
TI  - Risk, mobility or population size? Drivers of technological richness among
      contact-period western North American hunter-gatherers.
AB  - Identifying factors that influence technological evolution in small-scale
      societies is important for understanding human evolution. There have been a
      number of attempts to identify factors that influence the evolution of food
      getting technology, but little work has examined the factors that affect the
      evolution of other technologies. Here, we focus on variation in technological
      richness (total number of material items and techniques) among recent hunter
      gatherers from western North America and test three hypotheses: (i) technological
      richness is affected by environmental risk, (ii) population size is the primary
      determinant of technological richness, and (iii) technological richness is
      constrained by residential mobility. We found technological richness to be
      correlated with a proxy for environmental risk-mean rainfall for the driest month
      in the manner predicted by the risk hypothesis. Support for the hypothesis
      persisted when we controlled for shared history and intergroup contact. We found
      no evidence that technological richness is affected by population size or
      residential mobility. These results have important implications for unravelling
      the complexities of technological evolution. 

PMID- 24101623
TI  - Long-tailed macaques select mass of stone tools according to food type.
AB  - Tool selection can affect the success of a tool-based feeding task, and thus tool
      using animals should select appropriate tools when processing foods. We performed
      a field experiment on Piak Nam Yai Island in Laem Son National Park, Thailand, to
      test whether Burmese long-tailed macaques (Macaca fascicularis aurea) selected
      stone tools according to food type. We baited the island's shores with stone sets
      ('tool tests') in an effort to attract macaques to use stones presented in a
      quasi-experimental design. Tool tests were placed at 344 locations for 126 days
      over a 2 year period, with each set containing four stones of different mass
      (categories: X, 40-60 g; S, 90-100 g; M, 150-200 g; and L, 400-1000 g). Tool
      tests were checked when we could access them. The number of times each tool test
      was checked varied (1-32), for a total of 1950 checks. We also studied 375 non
      experimental stone tools that were found at naturally occurring tool-use sites.
      Our data were not collected by direct observation, but by inspecting stones after
      use. We found an association between stone mass and food type. In the tool tests,
      we found S-stones were chosen most often for attached oysters, and L-stones were
      chosen most often for unattached foods. L-stones were almost always chosen for
      larger unattached foods (greater than 3 cm length), while for smaller unattached
      foods (less than or equal to 3 cm length) selection was less skewed to L-stones
      and more evenly distributed between the M- and L-stone categories. In the non
      experimental study, we found that mass varied significantly across five food
      categories (range: 16-5166 g). We reveal more detail on macaque stone tool mass
      than previous studies, showing that macaques select differing stone masses across
      a variety of tool-processed foods. Our study is the first step in investigating
      the behavioural and cognitive mechanisms that macaques are using during tool
      selection.

PMID- 24101624
TI  - Tool making, hand morphology and fossil hominins.
AB  - Was stone tool making a factor in the evolution of human hand morphology? Is it
      possible to find evidence in fossil hominin hands for this capability? These
      questions are being addressed with increasingly sophisticated studies that are
      testing two hypotheses; (i) that humans have unique patterns of grip and hand
      movement capabilities compatible with effective stone tool making and use of the
      tools and, if this is the case, (ii) that there exist unique patterns of
      morphology in human hands that are consistent with these capabilities.
      Comparative analyses of human stone tool behaviours and chimpanzee feeding
      behaviours have revealed a distinctive set of forceful pinch grips by humans that
      are effective in the control of stones by one hand during manufacture and use of
      the tools. Comparative dissections, kinematic analyses and biomechanical studies
      indicate that humans do have a unique pattern of muscle architecture and joint
      surface form and functions consistent with the derived capabilities. A major
      remaining challenge is to identify skeletal features that reflect the full
      morphological pattern, and therefore may serve as clues to fossil hominin
      manipulative capabilities. Hominin fossils are evaluated for evidence of patterns
      of derived human grip and stress-accommodation features. 

PMID- 24101625
TI  - New Caledonian crows attend to multiple functional properties of complex tools.
AB  - The ability to attend to the functional properties of foraging tools should
      affect energy-intake rates, fitness components and ultimately the evolutionary
      dynamics of tool-related behaviour. New Caledonian crows Corvus moneduloides use
      three distinct tool types for extractive foraging: non-hooked stick tools, hooked
      stick tools and tools cut from the barbed edges of Pandanus spp. leaves. The
      latter two types exhibit clear functional polarity, because of (respectively) a
      single terminal, crow-manufactured hook and natural barbs running along one edge
      of the leaf strip; in each case, the 'hooks' can only aid prey capture if the
      tool is oriented correctly by the crow during deployment. A previous experimental
      study of New Caledonian crows found that subjects paid little attention to the
      barbs of supplied (wide) pandanus tools, resulting in non-functional tool
      orientation during foraging. This result is puzzling, given the presumed fitness
      benefits of consistently orienting tools functionally in the wild. We
      investigated whether the lack of discrimination with respect to (wide) pandanus
      tool orientation also applies to hooked stick tools. We experimentally provided
      subjects with naturalistic replica tools in a range of orientations and found
      that all subjects used these tools correctly, regardless of how they had been
      presented. In a companion experiment, we explored the extent to which normally co
      occurring tool features (terminal hook, curvature of the tool shaft and stripped
      bark at the hooked end) inform tool-orientation decisions, by forcing birds to
      deploy 'unnatural' tools, which exhibited these traits at opposite ends. Our
      subjects attended to at least two of the three tool features, although, as
      expected, the location of the hook was of paramount importance. We discuss these
      results in the context of earlier research and propose avenues for future work. 

PMID- 24101626
TI  - Ecological and social correlates of chimpanzee tool use.
AB  - The emergence of technology has been suggested to coincide with scarcity of
      staple resources that led to innovations in the form of tool-assisted strategies
      to diversify or augment typical diets. We examined seasonal patterns of several
      types of tool use exhibited by a chimpanzee (Pan troglodytes) population residing
      in central Africa, to determine whether their technical skills provided access to
      fallback resources when preferred food items were scarce. Chimpanzees in the
      Goualougo Triangle exhibit a diverse repertoire of tool behaviours, many of which
      are exhibited throughout the year. Further, they have developed specific tool
      sets to overcome the issues of accessibility to particular food items. Our
      conclusion is that these chimpanzees use a sophisticated tool technology to cope
      with seasonal changes in relative food abundance and gain access to high-quality
      foods. Subgroup sizes were smaller in tool using contexts than other foraging
      contexts, suggesting that the size of the social group may not be as important in
      promoting complex tool traditions as the frequency and type of social
      interactions. Further, reports from other populations and species showed that
      tool use may occur more often in response to ecological opportunities and
      relative profitability of foraging techniques than scarcity of resources.

PMID- 24101627
TI  - Hand before foot? Cortical somatotopy suggests manual dexterity is primitive and
      evolved independently of bipedalism.
AB  - People have long speculated whether the evolution of bipedalism in early hominins
      triggered tool use (by freeing their hands) or whether the necessity of making
      and using tools encouraged the shift to upright gait. Either way, it is commonly
      thought that one led to the other. In this study, we sought to shed new light on
      the origins of manual dexterity and bipedalism by mapping the neural
      representations in the brain of the fingers and toes of living people and
      monkeys. Contrary to the 'hand-in-glove' notion outlined above, our results
      suggest that adaptations underlying tool use evolved independently of those
      required for human bipedality. In both humans and monkeys, we found that each
      finger was represented separately in the primary sensorimotor cortex just as they
      are physically separated in the hand. This reflects the ability to use each digit
      independently, as required for the complex manipulation involved in tool use. The
      neural mapping of the subjects' toes differed, however. In the monkeys, the
      somatotopic representation of the toes was fused, showing that the digits
      function predominantly as a unit in general grasping. Humans, by contrast, had an
      independent neurological representation of the big toe (hallux), suggesting
      association with bipedal locomotion. These observations suggest that the brain
      circuits for the hand had advanced beyond simple grasping, whereas our primate
      ancestors were still general arboreal quadrupeds. This early adaptation laid the
      foundation for the evolution of manual dexterity, which was preserved and
      enhanced in hominins. In hominins, a separate adaptation, involving the neural
      separation of the big toe, apparently occurred with bipedality. This accords with
      the known fossil evidence, including the recently reported hominin fossils which
      have been dated to 4.4 million years ago.

PMID- 24101628
TI  - Did tool-use evolve with enhanced physical cognitive abilities?
AB  - The use and manufacture of tools have been considered to be cognitively demanding
      and thus a possible driving factor in the evolution of intelligence. In this
      study, we tested the hypothesis that enhanced physical cognitive abilities
      evolved in conjunction with the use of tools, by comparing the performance of
      naturally tool-using and non-tool-using species in a suite of physical and
      general learning tasks. We predicted that the habitually tool-using species, New
      Caledonian crows and Galapagos woodpecker finches, should outperform their non
      tool-using relatives, the small tree finches and the carrion crows in a physical
      problem but not in general learning tasks. We only found a divergence in the
      predicted direction for corvids. That only one of our comparisons supports the
      predictions under this hypothesis might be attributable to different complexities
      of tool-use in the two tool-using species. A critical evaluation is offered of
      the conceptual and methodological problems inherent in comparative studies on
      tool-related cognitive abilities. 

PMID- 24101630
TI  - Is primate tool use special? Chimpanzee and New Caledonian crow compared.
AB  - The chimpanzee (Pan troglodytes) is well-known in both nature and captivity as an
      impressive maker and user of tools, but recently the New Caledonian crow (Corvus
      moneduloides) has been championed as being equivalent or superior to the ape in
      elementary technology. I systematically compare the two taxa, going beyond simple
      presence/absence scoring of tool-using and -making types, on four more precise
      aspects of material culture: (i) types of associative technology (tools used in
      combination); (ii) modes of tool making; (iii) modes of tool use; and (iv)
      functions of tool use. I emphasize tool use in nature, when performance is
      habitual or customary, rather than in anecdotal or idiosyncratic. On all four
      measures, the ape shows more variety than does the corvid, especially in modes
      and functions that go beyond extractive foraging. However, more sustained field
      research is required on the crows before this contrast is conclusive.

PMID- 24101629
TI  - 'Captivity bias' in animal tool use and its implications for the evolution of
      hominin technology.
AB  - Animals in captive or laboratory settings may outperform wild animals of the same
      species in both frequency and diversity of tool use, a phenomenon here termed
      'captivity bias'. Although speculative at this stage, a logical conclusion from
      this concept is that animals whose tool-use behaviour is observed solely under
      natural conditions may be judged cognitively or physically inferior than if they
      had also been tested or observed under controlled captive conditions. In turn,
      this situation creates a potential problem for studies of the behaviour of
      extinct members of the human family tree-the hominins-as hominin cognitive
      abilities are often judged on material evidence of tool-use behaviour left in the
      archaeological record. In this review, potential factors contributing to
      captivity bias in primates (including increased contact between individuals
      engaged in tool use, guidance or shaping of tool-use behaviour by other tool
      users and increased free time and energy) are identified and assessed for their
      possible effects on the behaviour of the Late Pleistocene hominin Homo
      floresiensis. The captivity bias concept provides one way to uncouple hominin
      tool use from cognition, by considering hominins as subject to the same adaptive
      influences as other tool-using animals.

PMID- 24101631
TI  - Tool use by aquatic animals.
AB  - Tool-use research has focused primarily on land-based animals, with less
      consideration given to aquatic animals and the environmental challenges and
      conditions they face. Here, we review aquatic tool use and examine the
      contributing ecological, physiological, cognitive and social factors. Tool use
      among aquatic animals is rare but taxonomically diverse, occurring in fish,
      cephalopods, mammals, crabs, urchins and possibly gastropods. While additional
      research is required, the scarcity of tool use can likely be attributable to the
      characteristics of aquatic habitats, which are generally not conducive to tool
      use. Nonetheless, studying tool use by aquatic animals provides insights into the
      conditions that promote and inhibit tool-use behaviour across biomes. Like land
      based tool users, aquatic animals tend to find tools on the substrate and use
      tools during foraging. However, unlike on land, tool users in water often use
      other animals (and their products) and water itself as a tool. Among sea otters
      and dolphins, the two aquatic tool users studied in greatest detail, some
      individuals specialize in tool use, which is vertically socially transmitted
      possibly because of their long dependency periods. In all, the contrasts between
      aquatic- and land-based tool users enlighten our understanding of the adaptive
      value of tool-use behaviour. 

PMID- 24101633
TI  - Elongation as a factor in artefacts of humans and other animals: an Acheulean
      example in comparative context.
AB  - Elongation is a commonly found feature in artefacts made and used by humans and
      other animals and can be analysed in comparative study. Whether made for use in
      hand or beak, the artefacts have some common properties of length, breadth,
      thickness and balance point, and elongation can be studied as a factor relating
      to construction or use of a long axis. In human artefacts, elongation can be
      traced through the archaeological record, for example in stone blades of the
      Upper Palaeolithic (traditionally regarded as more sophisticated than earlier
      artefacts), and in earlier blades of the Middle Palaeolithic. It is now
      recognized that elongation extends to earlier Palaeolithic artefacts, being found
      in the repertoire of both Neanderthals and more archaic humans. Artefacts used by
      non-human animals, including chimpanzees, capuchin monkeys and New Caledonian
      crows show selection for diameter and length, and consistent interventions of
      modification. Both chimpanzees and capuchins trim side branches from stems, and
      appropriate lengths of stave are selected or cut. In human artefacts, occasional
      organic finds show elongation back to about 0.5 million years. A record of
      elongation achieved in stone tools survives to at least 1.75 Ma (million years
      ago) in the Acheulean tradition. Throughout this tradition, some Acheulean
      handaxes are highly elongated, usually found with others that are less elongated.
      Finds from the million-year-old site of Kilombe and Kenya are given as an
      example. These findings argue that the elongation need not be integral to a
      design, but that artefacts may be the outcome of adjustments to individual
      variables. Such individual adjustments are seen in animal artefacts. In the case
      of a handaxe, the maker must balance the adjustments to achieve a satisfactory
      outcome in the artefact as a whole. It is argued that the need to make decisions
      about individual variables within multivariate objects provides an essential
      continuity across artefacts made by different species. 

PMID- 24101632
TI  - If at first you don't succeed... Studies of ontogeny shed light on the cognitive
      demands of habitual tool use.
AB  - Many species use tools, but the mechanisms underpinning the behaviour differ
      between species and even among individuals within species, depending on the
      variants performed. When considering tool use 'as adaptation', an important first
      step is to understand the contribution made by fixed phenotypes as compared to
      flexible mechanisms, for instance learning. Social learning of tool use is
      sometimes inferred based on variation between populations of the same species but
      this approach is questionable. Specifically, alternative explanations cannot be
      ruled out because population differences are also driven by genetic and/or
      environmental factors. To better understand the mechanisms underlying routine but
      non-universal (i.e. habitual) tool use, we suggest focusing on the ontogeny of
      tool use and individual variation within populations. For example, if tool-using
      competence emerges late during ontogeny and improves with practice or varies with
      exposure to social cues, then a role for learning can be inferred. Experimental
      studies help identify the cognitive and developmental mechanisms used when tools
      are used to solve problems. The mechanisms underlying the route to tool-use
      acquisition have important consequences for our understanding of the accumulation
      in technological skill complexity over the life course of an individual, across
      generations and over evolutionary time. 

PMID- 24101637
TI  - Editorial committee introduction.

PMID- 24101638
TI  - Cholera epidemiology in Mozambique using national surveillance data.
AB  - BACKGROUND: Mozambique has experienced cholera for several decades. This study
      was undertaken to evaluate epidemiologic patterns to assist in guiding public
      health interventions. METHODS: We evaluated district-level Ministry of Health
      data for 123 consecutive weeks starting 1 January 2009. Cholera cases reported to
      the national level were based on clinical suspicion rather than microbiological
      confirmation. Time and space analyses with mapping and spatial statistics were
      undertaken. RESULTS: During 2009-2011, Mozambique identified 220 deaths among the
      25 431 reported suspected cholera cases (case fatality ratio [CFR], 0.87%). There
      were 108 outbreaks that occurred in 73 (50%) of Mozambique's 145 districts. Five
      distinct spatial clusters were identified involving inland and coastal as well as
      rural and urban populations. Among 78 outbreaks whose duration was known, average
      duration was 7.2 weeks (median, 6; range, 1-25). During weeks 1-3, 4-6, 7-9, and
      >= 10 after an outbreak, CFRs were 1.6%, 0.66%, 0.33%, and 0.25%, respectively.
      During 2010, districts that experienced an outbreak during 2009 had a CFR of 0.2%
      compared with 4.3% among other districts. DISCUSSION: Mozambique continues to
      experience widespread cholera outbreaks of short duration involving distinct
      spatial clusters. These findings will influence choice of public health
      strategies.

PMID- 24101639
TI  - National surveillance data on the epidemiology of cholera in Togo.
AB  - BACKGROUND: Togo is a cholera-endemic country bordered by other countries where
      this disease is endemic. We describe the epidemiology of cholera in Togo, using
      national surveillance data. METHODS: We reviewed national surveillance data
      housed in the National Ministry of Health. Districts submitted reports of summary
      weekly case counts and deaths at the national level. Data were available at the
      district level during 2008-2010 and at the national level from 1996 onward.
      Microbiological confirmation usually was not performed, and case identification
      was based on clinical suspicion. RESULTS: From 1996 through 2010, Togo had 12 676
      reported cholera cases and 554 deaths. Annual national cholera incidence varied
      from 0.9 to 66 cases per 100 000 population, with little variation except for 2
      large epidemics during 1998 and 2001. The case-fatality ratio declined from 12%
      17% during 1996-1997 to <1% during 2008-2010. During 2008-2010, 85% of 26
      district-level outbreaks occurred in the capital Lome or the coastal Maritime
      Region. The average outbreak duration was 6 weeks, and only 2 lasted >15 weeks.
      DISCUSSION: While cholera control remains elusive in Togo, reductions in case
      fatality ratios have occurred, possibly due to improvements in case management.
      The short duration of outbreaks may preclude reactive vaccination; however, the
      restricted geographic location may make preventive immunization attractive.

PMID- 24101640
TI  - Strategy, demand, management, and costs of an international cholera vaccine
      stockpile.
AB  - In this article, we review the feasibility of mass vaccination against cholera
      and estimate the global population at risk for epidemic cholera. We then examine
      the cost of establishing and managing a cholera vaccine stockpile and summarize
      published mathematical models of the estimated impact of reactive vaccination
      campaigns developed for the current Haitian outbreak and a recent outbreak in
      Zimbabwe. On the basis of these evaluations, we recommend a stockpile that starts
      at 2 million doses, with an estimated annual cost of $5.5-$13.9 million in 2013,
      and grows to 10 million doses per year by 2017, with an annual cost of $27-$51
      million. We believe that the stockpile can enhance efforts to mitigate future
      cholera outbreaks by guaranteeing the availability of cholera vaccines and,
      through use of the stockpile, by revealing knowledge about the efficient use of
      cholera vaccines during and after crises. 

PMID- 24101641
TI  - Diagnosis of Vibrio cholerae O1 infection in Africa.
AB  - Isolation of Vibrio cholerae O1 is necessary for cholera outbreak confirmation.
      Rapid diagnostic testing of fecal specimens, based on lipopolysaccharide
      detection of V. cholerae O1 or O139, may assist in early outbreak detection and
      surveillance. Cary-Blair transport medium is recommended for specimen transport.
      Filter paper, although used in epidemics, needs evaluation against rectal swab
      specimens. Fecal specimens are subcultured onto selective and nonselective media,
      including 5% blood agar and TCBS agar, for detection of V. cholerae O1 or O139.
      Suspicious, oxidase-positive isolates are serotyped in monovalent antisera.
      Antimicrobial-susceptibility testing is performed to detect resistance. Molecular
      characterization supports phenotypic identification and outbreak investigations.
      The presence of genes encoding cholera toxin, lipopolysaccharide, and El Tor
      biotype traits can be confirmed. Standardized pulsed-field gel electrophoresis
      analysis facilitates strain comparison. Quality management ensures reliability of
      results through validation and verification of functional laboratory equipment;
      quality control of testing procedures, laboratory reagents, and consumables; and
      participation in proficiency-testing schemes. 

PMID- 24101642
TI  - The role of Vibrio cholerae genotyping in Africa.
AB  - Toxigenic Vibrio cholerae, the causative agent of the disease cholera, is
      prevalent in the African continent from the 1970s when the seventh pandemic
      spread from Asia to Africa. In the past decade, cholera has caused devastating
      outbreaks in much of Africa, illustrated by the recent cholera epidemics in
      Zimbabwe and regions of central Africa. Given the extent of cholera in Africa, a
      robust and efficient surveillance system should be in place to prevent and
      control the disease in this continent. Such a surveillance system would be
      greatly bolstered by use of molecular typing techniques to identify genetic
      subtypes. In this review, we highlight the role that modern molecular typing
      techniques can play in tracking and aborting the spread of cholera. 

PMID- 24101643
TI  - Cholera outbreak in South Africa, 2008-2009: laboratory analysis of Vibrio
      cholerae O1 strains.
AB  - BACKGROUND: A total of 720 Vibrio cholerae O1 strains were recovered for
      investigation from an outbreak of cholera in South Africa between November 2008
      and April 2009. METHODS: Strains were characterized by serotype testing.
      Antimicrobial susceptibility testing. Genetic diversity of 248 strains was
      investigated using pulsed-field gel electrophoresis (PFGE) analysis. Extended
      characterization was performed on 90 strains. Molecular analysis included:
      polymerase chain reaction (PCR) identification of ctxA and tcpA genes, sequencing
      the ctxAB gene, and investigation of molecular mechanisms conferring
      antimicrobial resistance. RESULTS: The majority of strains were characterized as
      serotype Ogawa. Strains showed multidrug resistance. Approximately 1.0% of
      strains displayed extended-spectrum beta-lactamase (ESBL) activity. Strains
      showed very similar PFGE patterns. Ninety strains selected for extended
      characterization showed the following results: Strains possessed the cholera
      toxin (CT) and all were PCR positive for the tcpA-El Tor variant. Sequencing of
      the ctxB gene matched the B-1 allele. Strains harbored the SXT element. Strains
      that displayed ESBL activity possessed a 140-kilobase-pair plasmid that produced
      the TEM-63 beta-lactamase. Nalidixic acid-resistant strains harbored mutations in
      GyrA (Ser83-Ile) and ParC (Ser85-Leu). CONCLUSIONS: These data highlight the
      rapid development of antimicrobial resistance and spread of V. cholerae O1 El Tor
      variants expressing the classical CT within South Africa.

PMID- 24101644
TI  - Cholera in Africa: a closer look and a time for action.

PMID- 24101645
TI  - Environmental determinants of cholera outbreaks in inland Africa: a systematic
      review of main transmission foci and propagation routes.
AB  - Cholera is generally regarded as the prototypical waterborne and environmental
      disease. In Africa, available studies are scarce, and the relevance of this
      disease paradigm is questionable. Cholera outbreaks have been repeatedly reported
      far from the coasts: from 2009 through 2011, three-quarters of all cholera cases
      in Africa occurred in inland regions. Such outbreaks are either influenced by
      rainfall and subsequent floods or by drought- and water-induced stress. Their
      concurrence with global climatic events has also been observed. In lakes and
      rivers, aquatic reservoirs of Vibrio cholerae have been evocated. However, the
      role of these reservoirs in cholera epidemiology has not been established.
      Starting from inland cholera-endemic areas, epidemics burst and spread to various
      environments, including crowded slums and refugee camps. Human displacements
      constitute a major determinant of this spread. Further studies are urgently
      needed to better understand these complex dynamics, improve water and sanitation
      efforts, and eliminate cholera from Africa. 

PMID- 24101646
TI  - National surveillance data on the epidemiology of cholera in Kenya, 1997-2010.
AB  - BACKGROUND: Kenya has experienced multiple cholera outbreaks since 1971. Cholera
      remains an issue of major public health importance and one of the 35 priority
      diseases under Kenya's updated Integrated Disease Surveillance and Response
      strategy. METHODS: We reviewed the cholera surveillance data reported to the
      World Health Organization and the Kenya Ministry of Public Health and Sanitation
      from 1997 through 2010 to determine trends in cholera disease for the 14-year
      period. RESULTS: A total of 68 522 clinically suspected cases of cholera and 2641
      deaths were reported (overall case-fatality rate [CFR], 3.9%), affecting all
      regions of the country. Kenya's largest outbreak occurred during 1997-1999,
      resulting in 26 901 cases and 1362 deaths (CFR, 5.1%). Following a decline in
      disease occurrence, the country experienced a resurgence of epidemic cholera
      during 2007-2009 (16 616 cases and 454 deaths; CFR, 2.7%), which declined rapidly
      to 0 cases. Cases were reported through July 2010, with no cases reported during
      the second half of the year. About 42% of cases occurred in children aged <15
      years. Vibrio cholerae O1, serotype Inaba, was the predominant strain recorded
      from 2007 through 2010, although serotype Ogawa was also isolated. Recurrent
      outbreaks have most frequently affected Nairobi, Nyanza, and Coast provinces, as
      well as remote arid and semiarid regions and refugee camps. DISCUSSION: Kenya has
      experienced substantial amounts of reported cases of cholera during the past 14
      years. Recent decreases in cholera case counts may reflect cholera control
      measures put in place by the National Ministry of Health; confirmation of this
      theory will require ongoing surveillance.

PMID- 24101647
TI  - Evaluation of a rapid cholera response activity--Nyanza Province, Kenya, 2008.
AB  - BACKGROUND: In response to recurrent cholera outbreaks in Nyanza Province, Kenya,
      a local nongovernmental organization assisted the Ministry of Health by providing
      cholera education activities to some cholera-affected communities. We evaluated
      the impact on cholera prevention knowledge and practices. METHODS: In November
      December 2008, we conducted a cross-sectional household survey and tested stored
      water for chlorine in 6 cholera-affected enumeration areas (intervention-EAs)
      where response activities had occurred between March-September 2008, and 6
      comparison-EAs with no known reports of cholera outbreaks or response activities.
      RESULTS: We enrolled 358 individuals from intervention-EAs and 365 from
      comparison-EAs. Overall, >80% knew cholera symptoms and over 60% knew that water
      treatment prevented diarrhea; <20% had chlorine residual in stored water. More
      intervention-EA respondents than comparison-EA respondents recalled a cholera
      outbreak in their community (52% vs 19%, P < .0001), and of those, 51% versus
      39%, respectively, had attended a cholera response event. Detectable chlorine
      residuals in stored water were found in a higher percentage of intervention-EA
      and comparison-EA event attendees (21% and 25%, respectively) than nonattendees
      (17% and 8%, respectively). CONCLUSIONS: There was a gap between knowledge and
      practice of water treatment as a cholera preventive measure. Cholera event
      attendance may have modestly motivated increased household water treatment.

PMID- 24101648
TI  - A national cholera epidemic with high case fatality rates--Kenya 2009.
AB  - BACKGROUND: Cholera remains endemic in sub-Saharan Africa. We characterized the
      2009 cholera outbreaks in Kenya and evaluated the response. METHODS: We analyzed
      surveillance data and estimated case fatality rates (CFRs). Households in 2
      districts, East Pokot (224 cases; CFR = 11.7%) and Turkana South (1493 cases; CFR
      = 1.0%), were surveyed. We randomly selected 15 villages and 8 households per
      village in each district. Healthcare workers at 27 health facilities (HFs) were
      surveyed in both districts. RESULTS: In 2009, cholera outbreaks caused a reported
      11 425 cases and 264 deaths in Kenya. Data were available from 44 districts for
      6893 (60%) cases. District CFRs ranged from 0% to 14.3%. Surveyed household
      respondents (n = 240) were aware of cholera (97.5%) and oral rehydration solution
      (ORS) (87.9%). Cholera deaths were reported more frequently from East Pokot (n =
      120) than Turkana South (n = 120) households (20.7% vs. 12.3%). The average
      travel time to a HF was 31 hours in East Pokot compared with 2 hours in Turkana
      South. Fewer respondents in East Pokot (9.8%) than in Turkana South (33.9%)
      stated that ORS was available in their village. ORS or intravenous fluid
      shortages occurred in 20 (76.9%) surveyed HFs. CONCLUSIONS: High CFRs in Kenya
      are related to healthcare access disparities, including availability of
      rehydration supplies.

PMID- 24101649
TI  - Cholera surveillance in Uganda: an analysis of notifications for the years 2007
      2011.
AB  - INTRODUCTION: Cholera outbreaks have occurred periodically in Uganda since 1971.
      The country has experienced intervals of sporadic cases and localized outbreaks,
      occasionally resulting in prolonged widespread epidemics. METHODS: Cholera
      surveillance data reported to the Uganda Ministry of Health from 2007 through
      2011 were reviewed to determine trends in annual incidence and case fatality
      rate. Demographic characteristics of cholera cases were analyzed from the
      national line list for 2011. Cases were analyzed by district and month of report
      to understand the geographic distribution and identify any seasonal patterns of
      disease occurrence. RESULTS: From 2007 through 2011, Uganda registered a total of
      7615 cholera cases with 181 deaths (case fatality rate = 2.4%). The absolute
      number of cases and incidence per 100 000 varied from year to year with the
      highest incidence occurring in 2008 following heavy rainfall and flooding in
      eastern Uganda. For 2011, cholera cases occurred in 1.6 times more males than
      females. The geographical areas affected by the outbreaks shifted each year, with
      the exception of a few endemic districts. No clear seasonal trends in cholera
      occurrence were identified for this time period. CONCLUSIONS: We observed an
      overall decline in cases reported during the 5 years under review. During this
      period, concerted efforts were made by the Ugandan government and development
      partners to educate communities on proper sanitation and hygiene and provide safe
      water and timely treatment. Mechanisms to ensure timely and complete cholera
      surveillance data are reported to the national level should continue to be
      strengthened.

PMID- 24101650
TI  - The value of and challenges for cholera vaccines in Africa.
AB  - The 21st century saw a shift in the cholera burden from Asia to Africa. The risk
      factors for cholera outbreaks in Africa are incompletely understood, and the
      traditional emphasis on providing safe drinking water and improving sanitation
      and hygiene has proven remarkably insufficient to contain outbreaks. Current
      killed whole-cell oral cholera vaccines (OCVs) are safe and guarantee a high
      level of protection for several years. OCVs have been licensed for >20 years, but
      their potential for preventing and control cholera outbreaks in Africa has not
      been realized. Although each item in the long list of technical reasons why
      cholera vaccination campaigns have been deferred is plausible, we believe that
      the biggest barrier is that populations affected by cholera outbreaks are
      underprivileged and lack a strong political voice. The evaluation and use of OCVs
      as a tool for cholera control will require a new, more compassionate, less risk
      averse generation of decision makers. 

PMID- 24101652
TI  - National surveillance data on the epidemiology of cholera in Cameroon.
AB  - Background. The cholera burden in Cameroon has increased during the past 2
      decades. During 2010 and 2011, the largest number of cholera cases in Cameroon
      since February 1971 were reported. This article describes cholera outbreaks
      during 2010-2011. Methods. Data received from the national surveillance system
      from 2010 and 2011 were compiled and analyzed. Results. The first suspected
      cholera cases were reported in the Far North region on 6 May 2010. In 2010, 10
      759 cholera cases were reported by 8 of the 10 regions in the country, with 657
      deaths (case-fatality ratio [CFR], 6.1%). In 2011, through September 22, 17 121
      suspected cholera cases, including 636 deaths (CFR, 3.7%), were reported all over
      the country. During 2010, the Far North region accounted for 87.6% of cases
      (9421/10 759) and 91.6% of deaths (602/657) recorded. By contrast, during 2011, 5
      regions (Far North, North, Center, Southwest, and Littoral) accounted for 90.6%
      of cases (15 511/17 121) and 84.0% of deaths recorded. Vibrio cholerae was
      identified in 525 stool specimens, and all organisms were serogroup O1.
      Conclusions. The ongoing cholera outbreak in Cameroon increased in intensity and
      geographic spread from 2010 to 2011. Nevertheless, the overall CFR decreased
      during this period. Strengthening the early warning system and enhancing water,
      sanitation, and hygiene interventions and sensitization should be considered in
      addressing cholera outbreaks. 

PMID- 24101651
TI  - Elimination of cholera in the democratic Republic of the Congo: the new national
      policy.
AB  - We evaluated published and unpublished data on cholera cases and deaths reported
      from clinical care facilities in the 56 health districts of the Democratic
      Republic of Congo to the National Ministry of Health during 2000-2011. Cholera
      incidence was highest in the eastern provinces bordering lakes and epidemics
      primarily originated in this region. Along with a strong seasonal component, our
      data suggest a potential Vibrio cholerae reservoir in the Rift Valley lakes and
      the possible contribution of the lakes' fishing industry to the spread of
      cholera. The National Ministry of Health has committed to the elimination-rather
      than control-of cholera in DRC and has adopted a new national policy built on
      improved alert, response, case management, and prevention. To achieve this goal
      and implement all these measures it will require strong partners in the
      international community with a similar vision. 

PMID- 24101653
TI  - Cholera in coastal Africa: a systematic review of its heterogeneous environmental
      determinants.
AB  - According to the "cholera paradigm," epidemiology of this prototypical waterborne
      disease is considered to be driven directly by climate-induced variations in
      coastal aquatic reservoirs of Vibrio cholerae. This systematic review on
      environmental determinants of cholera in coastal Africa shows that instead
      coastal epidemics constitute a minor part of the continental cholera burden. Most
      of coastal cholera foci are located near estuaries, lagoons, mangrove forests,
      and on islands. Yet outbreaks often originate in coastal cities, where cholera is
      more likely to be imported from distant areas. Cholera outbreaks also may
      intensify in densely populated slum quarters before spreading to adjacent
      regions. Frequent seasonality of cholera incidence appears driven by the rainfall
      induced contamination of unprotected water sources through latrine overflow and
      sewage, as well as by the periodicity of human activities like fishing or
      traveling. Lulls in transmission periods of several years are repeatedly recorded
      even in high-risk coastal areas. To date, environmental studies have failed to
      demonstrate a perennial aquatic reservoir of toxigenic V. cholerae around the
      continent. Finally, applicability of the cholera paradigm therefore appears
      questionable in Africa, although available data remain limited. Thorough surveys
      with microbiological analyses of water samples and prospective genotyping of
      environmental and clinical strains of V. cholerae are needed to understand
      determinants of cholera in coastal Africa and better target prevention and
      control measures. 

PMID- 24101654
TI  - A comparative study of the biological effectiveness of 14-MeV neutron pulse and
      continuous radiation using mouse melanoma B-16 cells.
AB  - The study was carried out using compact neutron generators with a sealed tube
      operating in pulsed (neutron generator ING-031) and continuous (NG-14) modes.
      Neutron radiation was formed due to reaction T(d,n)(4)He. The average flow of 14
      MeV neutrons was 6.6*10(9) ns(-1) for ING-031 and 1.2-1.6*10(10) n s(-1) for NG
      14. Duration of an impulse was ~1 ms and pulse frequency of 50 Hz. The gamma rays
      of (60)So source with an average energy of 1.25 MeV were standard radiation.
      Biological efficacy was estimated using the clonogenic activity of mice melanoma
      B-16 cells. Comparison of biological effects of neutron irradiation in pulse and
      continuous modes showed no significant difference between them. RBE values of
      pulse (ING-031) and continuous (NG-14) neutron radiation were equal-in the range
      of 2.4-2.6. According to the clonogenic activity of melanoma B-16 cells no dose
      rate effect was observed within the studied range of neutrons doses and dose
      rates. 

PMID- 24101655
TI  - Thermoluminescence responses of terbium-doped magnesium orthosilicate with
      different synthesis conditions.
AB  - Numerous materials have been proposed for thermoluminescence dosemeter, and the
      example of highest sensitivity is cited as magnesium orthosilicate doped with
      terbium (Mg2SiO4:Tb). Nevertheless, the material is currently not commercially
      attractive because the sensitivity varies greatly with synthesis techniques. This
      is a multi-parameter problem, and the current work explores some of the
      conditions required to consistently enhance the response. These new results show
      that to get a high TL response, Mg2SiO4:Tb should be prepared at a high
      temperature of at least 1500 degrees C, for sintering times of several hours. In
      the current example, the optimum time was 6 h. Signals also vary with the terbium
      activator concentration, and good responses were achieved with a concentration of
      Tb at 5 wt %. Overall, this suggests that with careful preparation, the
      potentially high dosimetry performance might be exploited. The inherent problem
      of concentration quenching is considered, and the potential benefits of
      processing the powder with pulse laser annealing are reviewed in the light of
      successful luminescence and laser studies for rare-earth-doped laser materials. 

PMID- 24101657
TI  - The dependence of lipid asymmetry upon polar headgroup structure.
AB  - The effect of lipid headgroup structure upon the stability of lipid asymmetry was
      investigated. Using methyl-beta-cyclodextrin -induced lipid exchange,
      sphingomyelin (SM) was introduced into the outer leaflets of lipid vesicles
      composed of phosphatidylglycerol, phosphatidylserine (PS), phosphatidylinositol,
      or cardiolipin, in mixtures of all of these lipids with phosphatidylethanolamine
      (PE), and in a phosphatidylcholine/phosphatidic acid mixture. Efficient SM
      exchange (>85% of that expected for complete replacement of the outer leaflet)
      was obtained for every lipid composition studied. Vesicles containing PE mixed
      with anionic lipids showed nearly complete asymmetry which did not decay after 1
      day of incubation. However, vesicles containing anionic lipids without PE
      generally only exhibited partial asymmetry, which further decayed after 1 day of
      incubation. Vesicles containing the anionic lipid PS were an exception, showing
      nearly complete and stable asymmetry. It is likely that the combination of
      multiple charged groups on PE and PS inhibit transverse diffusion of these lipids
      across membranes relative to those lipids that only have one anionic group.
      Possible explanations of this behavior are discussed. The asymmetry properties of
      PE and PS may explain some of their functions in plasma membranes. 

PMID- 24101659
TI  - A new exercise central hemodynamics paradigm: time for reflection or expansion?

PMID- 24101656
TI  - Oncological outcomes of metastatic testicular cancers under centralized
      management through regional medical network.
AB  - OBJECTIVE: To investigate the dose intensity of induction chemotherapy and
      oncological outcomes of metastatic testicular cancer under centralized management
      through a regional medical network. MATERIALS AND METHODS: We retrospectively
      analyzed the outcomes of 86 metastatic testicular cancer patients who were given
      induction chemotherapy at Tsukuba University Hospital and four branch hospitals
      between January 2000 and November 2010. Principally, management of patients with
      poor-prognosis disease and patients having risk factors for bleomycin, etoposide
      and cisplatin were referred to Tsukuba University Hospital before chemotherapy.
      For high-risk groups, etoposide and cisplatin or etoposide, ifosfamide and
      cisplatin was used as an alternative to bleomycin, etoposide and cisplatin.
      RESULTS: Overall, 56 and 30 patients were treated at Tsukuba University Hospital
      and branch hospitals, respectively. Forty-seven, 18 and 21 patients were
      classified with good-, intermediate- and poor-prognosis disease, respectively,
      according to the International Germ Cell Cancer Collaborative Group criteria.
      Eighteen of the 21 patients (86%) with poor-prognosis disease were treated at
      Tsukuba University Hospital from the beginning of induction chemotherapy.
      Induction chemotherapy with a high relative dose intensity was possible in most
      patients. The average relative dose intensity of each drug was >0.96. Treatment
      procedures other than induction chemotherapy were efficiently centralized; 74% of
      post-chemotherapy surgery and all second-line or subsequent chemotherapies were
      performed at Tsukuba University Hospital. The 5-year overall survival rates of
      the good-, intermediate- and poor-prognosis groups were 97, 93 and 84%,
      respectively. CONCLUSIONS: Induction chemotherapy with high relative dose
      intensity, post-chemotherapy surgery and salvage chemotherapy was accomplished
      efficiently through centralization of management. Oncological outcomes were
      excellent, especially in patients with poor-prognosis disease, whose 5-year OS
      reached 84%.

PMID- 24101660
TI  - Glucocorticoid protection against myocardial ischemia-reperfusion injury: central
      role for the PGD2-Nrf2 pathway.

PMID- 24101661
TI  - Cellular fetal microchimerism in preeclampsia.
AB  - Previous studies have shown elevated concentrations of free fetal DNA and
      erythroblasts in maternal circulation in women with preeclampsia compared with
      those with normal pregnancy. Pluripotent and immunocompetent fetal cells also
      transfer to the maternal circulation during pregnancy, but whether concentrations
      of fetal mononuclear cells also differed in preeclampsia was unknown. We sought
      to quantify cellular fetal microchimerism in maternal circulation in women with
      preeclampsia and healthy controls. We studied women with preeclampsia and
      compared them with women with healthy pregnancies at similar gestational age. To
      identify a targetable polymorphism unique to the fetus to quantify fetal
      microchimerism, participants and family members were genotyped for the human
      leukocyte antigen loci DRB1, DQA1, and DQB1, as well as several other
      polymorphisms. A panel of polymorphism-specific quantitative polymerase chain
      reaction assays was used to identify and quantify fetal microchimerism in
      maternal peripheral blood mononuclear cells. Of 53 preeclampsia samples tested
      for cellular fetal microchimerism, 17 (32%) were positive when compared with 6 of
      57 (6%) control samples (unadjusted odds ratio for detection, 4.0; 95% confidence
      interval, 1.5-11.1; P=0.007). The concentration of cellular fetal microchimerism
      (expressed as genome equivalents of fetal microchimerism per 100,000 maternal
      genome equivalents) was also higher among women with preeclampsia: median 0.0,
      mean 5.7, range 0 to 153.7, compared with those with controls: median 0.0, mean
      0.3, range 0 to 9.1, P=0.002. We conclude that women with preeclampsia harbor
      cellular fetal microchimerism more commonly and at higher concentrations compared
      with women with uncomplicated pregnancy. The functional capacity and phenotype of
      these fetal cells are not yet known.

PMID- 24101662
TI  - Endogenous prostaglandin D2 and its metabolites protect the heart against
      ischemia-reperfusion injury by activating Nrf2.
AB  - We recently demonstrated that glucocorticoids markedly upregulate the expression
      of cyclooxygenase-2 in cardiomyocytes and protect hearts from ischemia
      reperfusion (I/R) injury by activating lipocalin-type prostaglandin D (PGD)
      synthase (L-PGDS)-derived PGD(2) biosynthesis. We examined a downstream mechanism
      of cardioprotection elicited by PGD(2) biosynthesis. Acute PGD(2) treatment did
      not protect hearts against I/R injury. We then speculated that PGD(2) and its
      metabolite 15-deoxy-Delta12,14-PGJ(2) activate gene expression networks to
      mediate the glucocorticoid-mediated cardioprotection. Using an unbiased approach,
      we identified that glucocorticoids induce a number of well-known erythroid
      derived 2-like 2 (Nrf2) target genes in the heart in an L-PGDS-dependent manner
      and that the cardioprotective effect of glucocorticoids against I/R injury was
      not seen in Nrf2-knockout hearts. We showed relatively low expression of PGD(2)
      receptors (ie, DP1 and DP2) in the heart but abundant expression of PGF(2alpha)
      receptor (FP), which binds PGF(2alpha) and PGD(2) with equal affinity.
      Glucocorticoids also failed to induce the expression of L-PGDS-dependent Nrf2
      target genes in FP-knockout hearts. PGD(2) acted through its metabolite 15-deoxy
      Delta12,14-PGJ(2) in the heart as evidenced by the glucocorticoid-mediated
      activation of peroxisome proliferator-activated receptor-gamma. In turn,
      glucocorticoids failed to induce the expression of L-PGDS-dependent Nrf2 target
      genes in hearts pretreated with peroxisome proliferator-activated receptor-gamma
      antagonist GW9662, and glucocorticoid-mediated cardioprotection against I/R
      injury was compromised in FP-knockout mice and GW9662-treated mice. In
      conclusion, PGD(2) protects heart against I/R injury by activating Nrf2
      predominantly via FP receptor. In addition, we propose activation of peroxisome
      proliferator-activated receptor-gamma by the dehydrated metabolite of PGD(2) (15
      deoxy-Delta12,14-PGJ(2)) as another mechanism by which glucocorticoids induce
      cardioprotection.

PMID- 24101663
TI  - Dietary and urinary metabonomic factors possibly accounting for higher blood
      pressure of black compared with white Americans: results of International
      Collaborative Study on macro-/micronutrients and blood pressure.
AB  - Black compared with non-Hispanic white Americans have higher systolic and
      diastolic blood pressure and rates of prehypertension/hypertension. Reasons for
      these adverse findings remain obscure. Analyses here focused on relations of
      foods/nutrients/urinary metabolites and higher black blood pressure for 369 black
      compared with 1190 non-Hispanic white Americans aged 40 to 59 years from 8
      population samples. Multiple linear regression, standardized data from four 24
      hour dietary recalls per person, two 24-hour urine collections, and 8 blood
      pressure measurements were used to quantitate the role of foods, nutrients, and
      metabolites in higher black blood pressure. Compared with non-Hispanic white
      Americans, blacks' average systolic/diastolic pressure was higher by 4.7/3.4 mm
      Hg (men) and 9.0/4.8 mm Hg (women). Control for higher body mass index of black
      women reduced excess black systolic/diastolic pressure to 6.8/3.8 mm Hg. Lesser
      intake of vegetables, fruits, grains, vegetable protein, glutamic acid, starch,
      fiber, minerals, and potassium, and higher intake of processed meats, pork, eggs,
      and sugar-sweetened beverages, along with higher cholesterol and higher Na/K
      ratio, related to in higher black blood pressure. Control for 11 nutrient and 10
      non-nutrient correlates reduced higher black systolic/diastolic pressure to
      2.3/2.3 mm Hg (52% and 33% reduction in men) and to 5.3/2.8 mm Hg (21% and 27%
      reduction in women). Control for foods/urinary metabolites had little further
      influence on higher black blood pressure. Less favorable multiple nutrient intake
      by blacks than non-Hispanic white Americans accounted, at least in part, for
      higher black blood pressure. Improved dietary patterns can contribute to
      prevention/control of more adverse black blood pressure levels.

PMID- 24101664
TI  - Novel role of the renin-angiotensin system in preeclampsia superimposed on
      chronic hypertension and the effects of exercise in a mouse model.
AB  - Gestational hypertensive disorders, such as preeclampsia, affect 6% to 8% of all
      pregnancies in North America, and they are the leading cause of maternal
      mortality in industrialized countries, accounting for 16% of deaths. Women with
      hypertension have an increased risk (15% to 25%) of developing preeclampsia. Our
      aim was to investigate the mechanisms implicated in preeclampsia superimposed on
      chronic hypertension and in the protective effects of exercise in a mouse model.
      Female mice overexpressing human angiotensinogen and human renin were used as a
      model of preeclampsia superimposed on chronic hypertension. In the trained group,
      mothers were placed in cages with access to a wheel before mating, and they
      remained within these throughout gestation. Blood pressure was measured by
      telemetry. We found that angiotensin II type I receptor was increased, whereas
      the Mas receptor was decreased in the placenta and the aorta of pregnant
      sedentary transgenic mice. This would produce a decrease in angiotensin-(1-7)
      effects in favor of angiotensin II. Supporting the functional contribution of
      this modulation, we found that the prevention of most pathological features in
      trained transgenic mice was associated with a normalization of placental
      angiotensin II type 1 and Mas receptors and an increase in aortic Mas receptor.
      We also found reduced circulating and placental soluble Fms-like tyrosine kinase
      1 in trained transgenic mice compared with sedentary mice. This study
      demonstrates that modulation of the renin-angiotensin system is a key mechanism
      in the development of preeclampsia superimposed on chronic hypertension, which
      can be altered by exercise training to prevent disease features in an animal
      model. 

PMID- 24101665
TI  - Potential clinical application of recently discovered brain mechanisms involved
      in hypertension.

PMID- 24101666
TI  - Potential therapeutic role of phosphodiesterase type 5 inhibition in hypertension
      and chronic kidney disease.

PMID- 24101667
TI  - In vivo transfection of manganese superoxide dismutase gene or nuclear factor
      kappaB shRNA in nodose ganglia improves aortic baroreceptor function in heart
      failure rats.
AB  - Arterial baroreflex sensitivity is attenuated in chronic heart failure (CHF)
      state, which is associated with cardiac arrhythmias and sudden cardiac death in
      patients with CHF. Our previous study showed that CHF-induced sodium channel
      dysfunction in the baroreceptor neurons was involved in the blunted baroreflex
      sensitivity in CHF rats. Mitochondria-derived superoxide overproduction decreased
      expression and activation of the sodium channels in the baroreceptor neurons from
      CHF rats. However, the molecular mechanisms responsible for the sodium channel
      dysfunction in the baroreceptor neurons from CHF rats remain unknown. We tested
      the involvement of nuclear factor kappaB (NFkappaB) in the sodium channel
      dysfunction and evaluated the effects of in vivo transfection of manganese
      superoxide dismutase gene and NFkappaB shRNA on the baroreflex function in CHF
      rats. CHF was developed at 6 to 8 weeks after left coronary artery ligation in
      adult rats. Western blot and chromatin immunoprecipitation data showed that
      phosphorylated NFkappaB p65 and ability of NFkappaB p65 binding to the sodium
      channel promoter were increased in the nodose ganglia from CHF rats. In vivo
      transfection of adenoviral manganese superoxide dismutase gene or lentiviral
      NFkappaB p65 shRNA into the nodose ganglia partially reversed CHF-reduced sodium
      channel expression and cell excitability in the baroreceptor neurons and improved
      CHF-blunted arterial baroreflex sensitivity. Additionally, transfection of
      adenoviral manganese superoxide dismutase also inhibited the augmentation of
      phosphorylated NFkappaB p65 in the nodose neurons from CHF rats. The present
      study suggests that superoxide-NFkappaB signaling contributes to CHF-induced
      baroreceptor dysfunction and resultant impairment of baroreflex function. 

PMID- 24101668
TI  - Dynamic cerebral autoregulation in pregnancy and the risk of preeclampsia.
AB  - Preeclampsia may affect severely the cerebral circulation leading to impairment
      of cerebral autoregulation, edema, and ischemia. It is not known whether impaired
      autoregulation occurs before the clinical onset of preeclampsia, and whether this
      can predict the occurrence of preeclampsia. Seventy-two women at 25 to 28 weeks
      of gestation were studied. Control values were derived from 26 nonpregnant women.
      Dynamic properties of cerebral autoregulation (DCA) were measured in the middle
      and posterior cerebral artery using transcranial Doppler and transfer function
      analysis (phase and gain) of respiratory-induced 0.1 Hz hemodynamic oscillations.
      Uterine artery ultrasound was performed to search for a notch sign as an early
      marker of general endothelial dysfunction. All women were followed up until 6
      weeks after delivery for the occurrence of preeclampsia. The autoregulation
      parameter gain did not differ between pregnant and nonpregnant women. Phase was
      slightly but significantly higher in pregnant women, indicating better DCA. Women
      with a notch sign did not show altered DCA. A history of preeclampsia during a
      previous pregnancy was associated with lower phase in middle cerebral artery and
      posterior cerebral artery (P<0.05 each). During follow-up, 9 women developed
      preeclampsia. None of the DCA parameters were associated with the occurrence of
      preeclampsia. In conclusion, DCA is well preserved during late midterm pregnancy,
      even in women with disturbed uterine blood flow. Yet, pregnant women with
      preeclampsia in a previous pregnancy seem to have poorer DCA. Although limited in
      statistical power, this study does not support DCA as a strong early risk marker
      of preeclampsia. 

PMID- 24101669
TI  - Signal regulatory protein-alpha protects against cardiac hypertrophy via the
      disruption of toll-like receptor 4 signaling.
AB  - Signal regulatory protein-alpha (SIRPA/SIRPalpha) is a transmembrane protein that
      is expressed in various tissues, including the heart. Previous studies have
      demonstrated that SIRPA is involved in multiple biological processes, including
      macrophage multinucleation, skeletal muscle differentiation, neuronal survival,
      protection against diabetes mellitus, and negative regulation of immune cells.
      However, the role of SIRPA in cardiac hypertrophy remains unknown. To examine the
      role of SIRPA in pathological cardiac hypertrophy, we used SIRPA knockout mice
      and transgenic mice that overexpressed mouse SIRPA in the heart. Cardiac
      hypertrophy was evaluated by echocardiographic, hemodynamic, pathological, and
      molecular analyses. We observed downregulation of SIRPA expression in dilated
      cardiomyopathy human hearts and in animal hearts after aortic banding surgery.
      Accordingly, SIRPA(-/-) mice displayed augmented cardiac hypertrophy, which was
      accompanied by increased cardiac fibrosis and reduced contractile function, as
      compared with SIRPA(+/+) mice 4 weeks after aortic banding. In contrast,
      transgenic mice with the cardiac-specific SIRPA overexpression exhibited the
      opposite phenotype in response to pressure overload. Likewise, SIRPA protected
      against angiotensin II-induced cardiomyocyte hypertrophy in vitro.
      Mechanistically, we revealed that SIRPA-mediated protection during cardiac
      hypertrophy involved inhibition of the Toll-like receptor 4/nuclear factor-kappaB
      signaling axis. Furthermore, we demonstrated that the disruption of Toll-like
      receptor 4 rescued the adverse effects of SIRPA deficiency on pressure overload
      triggered cardiac remodeling. Thus, our results identify that SIRPA plays a
      protective role in cardiac hypertrophy through negative regulation of the Toll
      like receptor 4/nuclear factor-kappaB pathway. 

PMID- 24101671
TI  - Concise review: guidance in developing commercializable autologous/patient
      specific cell therapy manufacturing.
AB  - Cell therapy is poised to play an enormous role in regenerative medicine.
      However, little guidance is being made available to academic and industrial
      entities in the start-up phase. In this technical review, members of the
      International Society for Cell Therapy provide guidance in developing
      commercializable autologous and patient-specific manufacturing strategies from
      the perspective of process development. Special emphasis is placed on providing
      guidance to small academic or biotech researchers as to what simple questions can
      be addressed or answered at the bench in order to make their cell therapy
      products more feasible for commercial-scale production. We discuss the processes
      that are required for scale-out at the manufacturing level, and how many
      questions can be addressed at the bench level. The goal of this review is to
      provide guidance in the form of topics that can be addressed early in the process
      of development to better the chances of the product being successful for future
      commercialization. 

PMID- 24101670
TI  - Concise review: ex vivo expansion of cord blood-derived hematopoietic stem and
      progenitor cells: basic principles, experimental approaches, and impact in
      regenerative medicine.
AB  - Hematopoietic stem cells (HSCs) and hematopoietic progenitor cells (HPCs) play
      key roles in the production of mature blood cells and in the biology and clinical
      outcomes of hematopoietic transplants. The numbers of these cells, however, are
      extremely low, particularly in umbilical cord blood (UCB); thus, ex vivo
      expansion of human UCB-derived HSCs and HPCs has become a priority in the
      biomedical field. Expansion of progenitor cells can be achieved by culturing such
      cells in the presence of different combinations of recombinant stimulatory
      cytokines; in contrast, expansion of actual HSCs has proved to be more difficult
      because, in addition to needing recombinant cytokines, HSCs seem to deeply depend
      on the presence of stromal cells and/or elements that promote the activation of
      particular self-renewal signaling pathways. Hence, there is still controversy
      regarding the optimal culture conditions that should be used to achieve this. To
      date, UCB transplants using ex vivo-expanded cells have already been performed
      for the treatment of different hematological disorders, and although results are
      still far from being optimal, the advances are encouraging. Recent studies
      suggest that HSCs may also give rise to nonhematopoietic cells, such as neural,
      cardiac, mesenchymal, and muscle cells. Such plasticity and the possibility of
      producing nonhematopoietic cells at the clinical scale could bring new
      alternatives for the treatment of neural, metabolic, orthopedic, cardiac, and
      neoplastic disorders. Once standardized, ex vivo expansion of human HSCs/HPCs
      will surely have a positive impact in regenerative medicine. 

PMID- 24101672
TI  - Genetic deletion and pharmacological inhibition of phosphodiesterase 10A protects
      mice from diet-induced obesity and insulin resistance.
AB  - Phosphodiesterase 10A (PDE10A) is a novel therapeutic target for the treatment of
      schizophrenia. Here we report a novel role of PDE10A in the regulation of caloric
      intake and energy homeostasis. PDE10A-deficient mice are resistant to diet
      induced obesity (DIO) and associated metabolic disturbances. Inhibition of weight
      gain is due to hypophagia after mice are fed a highly palatable diet rich in fats
      and sugar but not a standard diet. PDE10A deficiency produces a decrease in
      caloric intake without affecting meal frequency, daytime versus nighttime feeding
      behavior, or locomotor activity. We tested THPP-6, a small molecule PDE10A
      inhibitor, in DIO mice. THPP-6 treatment resulted in decreased food intake, body
      weight loss, and reduced adiposity at doses that produced antipsychotic efficacy
      in behavioral models. We show that PDE10A inhibition increased whole-body energy
      expenditure in DIO mice fed a Western-style diet, achieving weight loss and
      reducing adiposity beyond the extent seen with food restriction alone. Therefore,
      chronic THPP-6 treatment conferred improved insulin sensitivity and reversed
      hyperinsulinemia. These data demonstrate that PDE10A inhibition represents a
      novel antipsychotic target that may have additional metabolic benefits over
      current medications for schizophrenia by suppressing food intake, alleviating
      weight gain, and reducing the risk for the development of diabetes. 

PMID- 24101673
TI  - HDAC9 knockout mice are protected from adipose tissue dysfunction and systemic
      metabolic disease during high-fat feeding.
AB  - During chronic caloric excess, adipose tissue expands primarily by enlargement of
      individual adipocytes, which become stressed with lipid overloading, thereby
      contributing to obesity-related disease. Although adipose tissue contains
      numerous preadipocytes, differentiation into functionally competent adipocytes is
      insufficient to accommodate the chronic caloric excess and prevent adipocyte
      overloading. We report for the first time that a chronic high-fat diet (HFD)
      impairs adipogenic differentiation, leading to accumulation of inefficiently
      differentiated adipocytes with blunted expression of adipogenic differentiation
      specific genes. Preadipocytes from these mice likewise exhibit impaired
      adipogenic differentiation, and this phenotype persists during in vitro cell
      culture. HFD-induced impaired adipogenic differentiation is associated with
      elevated expression of histone deacetylase 9 (HDAC9), an endogenous negative
      regulator of adipogenic differentiation. Genetic ablation of HDAC9 improves
      adipogenic differentiation and systemic metabolic state during an HFD, resulting
      in diminished weight gain, improved glucose tolerance and insulin sensitivity,
      and reduced hepatosteatosis. Moreover, compared with wild-type mice, HDAC9
      knockout mice exhibit upregulated expression of beige adipocyte marker genes,
      particularly during an HFD, in association with increased energy expenditure and
      adaptive thermogenesis. These results suggest that targeting HDAC9 may be an
      effective strategy for combating obesity-related metabolic disease. 

PMID- 24101674
TI  - A genome-wide association study in American Indians implicates DNER as a
      susceptibility locus for type 2 diabetes.
AB  - Most genetic variants associated with type 2 diabetes mellitus (T2DM) have been
      identified through genome-wide association studies (GWASs) in Europeans. The
      current study reports a GWAS for young-onset T2DM in American Indians.
      Participants were selected from a longitudinal study conducted in Pima Indians
      and included 278 cases with diabetes with onset before 25 years of age, 295
      nondiabetic controls >=45 years of age, and 267 siblings of cases or controls.
      Individuals were genotyped on a ~1M single nucleotide polymorphism (SNP) array,
      resulting in 453,654 SNPs with minor allele frequency >0.05. SNPs were analyzed
      for association in cases and controls, and a family-based association test was
      conducted. Tag SNPs (n = 311) were selected for 499 SNPs associated with diabetes
      (P < 0.0005 in case-control analyses or P < 0.0003 in family-based analyses), and
      these SNPs were genotyped in up to 6,834 additional Pima Indians to assess
      replication. Rs1861612 in DNER was associated with T2DM (odds ratio = 1.29 per
      copy of the T allele; P = 6.6 * 10(-8), which represents genome-wide significance
      accounting for the number of effectively independent SNPs analyzed). Transfection
      studies in murine pancreatic beta-cells suggested that DNER regulates expression
      of notch signaling pathway genes. These studies implicate DNER as a
      susceptibility gene for T2DM in American Indians. 

PMID- 24101675
TI  - SLC30A8 nonsynonymous variant is associated with recovery following exercise and
      skeletal muscle size and strength.
AB  - Genome-wide association studies have identified thousands of variants that are
      associated with numerous phenotypes. One such variant, rs13266634, a
      nonsynonymous single nucleotide polymorphism in the solute carrier family 30
      (zinc transporter) member eight gene, is associated with a 53% increase in the
      risk of developing type 2 diabetes (T2D). We hypothesized that individuals with
      the protective allele against T2D would show a positive response to short-term
      and long-term resistance exercise. Two cohorts of young adults-the Eccentric
      Muscle Damage (EMD; n = 156) cohort and the Functional Single Nucleotide
      Polymorphisms Associated with Muscle Size and Strength Study (FAMuSS; n = 874)
      were tested for association of the rs13266634 variant with measures of skeletal
      muscle response to resistance exercise. Our results were sexually dimorphic in
      both cohorts. Men in the EMD study with two copies of the protective allele
      showed less post-exercise bout strength loss, less soreness, and lower creatine
      kinase values. In addition, men in the FAMuSS, homozygous for the protective
      allele, showed higher pre-exercise strength and larger arm skeletal muscle
      volume, but did not show a significant difference in skeletal muscle hypertrophy
      or strength with resistance training. 

PMID- 24101676
TI  - Constitutively active CaMKKalpha stimulates skeletal muscle glucose uptake in
      insulin-resistant mice in vivo.
AB  - In insulin-sensitive skeletal muscle, the expression of constitutively active
      Ca(2+)/calmodulin-dependent protein kinase kinase alpha (caCaMKKalpha) stimulates
      glucose uptake independent of insulin signaling (i.e., Akt and Akt-dependent
      TBC1D1/TBC1D4 phosphorylation). Our objectives were to determine whether
      caCaMKKalpha could stimulate glucose uptake additively with insulin in insulin
      sensitive muscle, in the basal state in insulin-resistant muscle, and if so, to
      determine whether the effects were associated with altered TBC1D1/TBC1D4
      phosphorylation. Mice were fed a control or high-fat diet (60% kcal) for 12 weeks
      to induce insulin resistance. Muscles were transfected with empty vector or
      caCaMKKalpha plasmids using in vivo electroporation. After 2 weeks, caCaMKKalpha
      protein was robustly expressed. In insulin-sensitive muscle, caCaMKKalpha
      increased basal in vivo [(3)H]-2-deoxyglucose uptake approximately twofold,
      insulin increased glucose uptake approximately twofold, and caCaMKKalpha plus
      insulin increased glucose uptake approximately fourfold. caCaMKKalpha did not
      increase basal TBC1D1 (Ser(237), Thr(590), Ser(660), pan-Thr/Ser) or TBC1D4
      (Ser(588), Thr(642), pan-Thr/Ser) phosphorylation. In insulin-resistant muscle,
      caCaMKKalpha increased basal glucose uptake approximately twofold, and attenuated
      high-fat diet-induced basal TBC1D1 (Thr(590), pan-Thr/Ser) and TBC1D4 (Ser(588),
      Thr(642), pan-Thr/Ser) phosphorylation. In cell-free assays, CaMKKalpha increased
      TBC1D1 (Thr(590), pan-Thr/Ser) and TBC1D4 (Ser(588), pan-Thr/Ser)
      phosphorylation. Collectively, these results demonstrate that caCaMKKalpha
      stimulates glucose uptake additively with insulin, and in insulin-resistant
      muscle, and alters the phosphorylation of TBC1D1/TBC1D4. 

PMID- 24101677
TI  - Podocyte-specific GLUT4-deficient mice have fewer and larger podocytes and are
      protected from diabetic nephropathy.
AB  - Podocytes are a major component of the glomerular filtration barrier, and their
      ability to sense insulin is essential to prevent proteinuria. Here we identify
      the insulin downstream effector GLUT4 as a key modulator of podocyte function in
      diabetic nephropathy (DN). Mice with a podocyte-specific deletion of GLUT4 (G4
      KO) did not develop albuminuria despite having larger and fewer podocytes than
      wild-type (WT) mice. Glomeruli from G4 KO mice were protected from diabetes
      induced hypertrophy, mesangial expansion, and albuminuria and failed to activate
      the mammalian target of rapamycin (mTOR) pathway. In order to investigate whether
      the protection observed in G4 KO mice was due to the failure to activate mTOR, we
      used three independent in vivo experiments. G4 KO mice did not develop
      lipopolysaccharide-induced albuminuria, which requires mTOR activation. On the
      contrary, G4 KO mice as well as WT mice treated with the mTOR inhibitor rapamycin
      developed worse adriamycin-induced nephropathy than WT mice, consistent with the
      fact that adriamycin toxicity is augmented by mTOR inhibition. In summary, GLUT4
      deficiency in podocytes affects podocyte nutrient sensing, results in fewer and
      larger cells, and protects mice from the development of DN. This is the first
      evidence that podocyte hypertrophy concomitant with podocytopenia may be
      associated with protection from proteinuria. 

PMID- 24101679
TI  - PRRT2 mutations: exploring the phenotypical boundaries.
AB  - BACKGROUND: Mutations in the proline-rich transmembrane protein 2 (PRRT2) gene
      have been identified in patients with benign (familial) infantile convulsions
      (B(F)IC), infantile convulsions with choreoathetosis (ICCA) and paroxysmal
      dyskinesias (PDs). However it remains unknown whether PRRT2 mutations are causal
      in other epilepsy syndromes. After we discovered a PRRT2 mutation in a large
      family with ICCA containing one individual with febrile seizures (FS) and one
      individual with West syndrome, we analysed PRRT2 in a heterogeneous cohort of
      patients with different types of infantile epilepsy. METHODS: We screened a
      cohort of 460 patients with B(F)IC or ICCA, fever related seizures or infantile
      epileptic encephalopathies. All patients were tested for point mutations using
      direct sequencing. RESULTS: We identified heterozygous mutations in 16
      individuals: 10 familial and 6 sporadic cases. All patients were diagnosed with
      B(F)IC, ICCA or PD. We were not able to detect mutations in any of the other
      epilepsy syndromes. Several mutation carriers had learning disabilities and/or
      impaired fine motor skills later in life. CONCLUSIONS: PRRT2 mutations do not
      seem to be involved in the aetiology of FS or infantile epileptic
      encephalopathies. Therefore B(F)IC, ICCA and PD remain the core phenotypes
      associated with PRRT2 mutations. The presence of learning disabilities or
      neuropsychiatric problems in several mutation carriers calls for additional
      clinical studies addressing this developmental aspect in more detail.

PMID- 24101678
TI  - Autism traits in the RASopathies.
AB  - BACKGROUND: Mutations in Ras/mitogen-activated protein kinase (Ras/MAPK) pathway
      genes lead to a class of disorders known as RASopathies, including
      neurofibromatosis type 1 (NF1), Noonan syndrome (NS), Costello syndrome (CS), and
      cardio-facio-cutaneous syndrome (CFC). Previous work has suggested potential
      genetic and phenotypic overlap between dysregulation of Ras/MAPK signalling and
      autism spectrum disorders (ASD). Although the literature offers conflicting
      evidence for association of NF1 and autism, there has been no systematic
      evaluation of autism traits in the RASopathies as a class to support a role for
      germline Ras/MAPK activation in ASDs. METHODS: We examined the association of
      autism traits with NF1, NS, CS and CFC, comparing affected probands with
      unaffected sibling controls and subjects with idiopathic ASDs using the
      qualitative Social Communication Questionnaire (SCQ) and the quantitative Social
      Responsiveness Scale (SRS). RESULTS: Each of the four major RASopathies showed
      evidence for increased qualitative and quantitative autism traits compared with
      sibling controls. Further, each RASopathy exhibited a distinct distribution of
      quantitative social impairment. Levels of social responsiveness show some
      evidence of correlation between sibling pairs, and autism-like impairment showed
      a male bias similar to idiopathic ASDs. CONCLUSIONS: Higher prevalence and
      severity of autism traits in RASopathies compared to unaffected siblings suggests
      that dysregulation of Ras/MAPK signalling during development may be implicated in
      ASD risk. Evidence for sex bias and potential sibling correlation suggests that
      autism traits in the RASopathies share characteristics with autism traits in the
      general population and clinical ASD population and can shed light on idiopathic
      ASDs.

PMID- 24101680
TI  - Health care quality improvement publication trends.
AB  - To analyze the extent of academic interest in quality improvement (QI)
      initiatives in medical practice, annual publication trends for the most well
      known QI methodologies being used in health care settings were analyzed. A total
      of 10 key medical- and business-oriented library databases were examined: PubMed,
      Ovid MEDLINE, EMBASE, CINAHL, PsycINFO, ISI Web of Science, Scopus, the Cochrane
      Central Register of Controlled Trials, ABI/INFORM, and Business Source Complete.
      A total of 13 057 articles were identified that discuss at least 1 of 10 well
      known QI concepts used in health care contexts, 8645 (66.2%) of which were
      classified as original research. "Total quality management" was the only
      methodology to demonstrate a significant decline in publication over time.
      "Continuous quality improvement" was the most common topic of study across all
      publication years, whereas articles discussing Lean methodology demonstrated the
      largest growth in publication volume over the past 2 decades. Health care QI
      publication volume increased substantially beginning in 1991. 

PMID- 24101681
TI  - The differences between doctors' and nurses' attitudes toward adverse event
      reporting and assessments of factors that inhibit reporting.

PMID- 24101682
TI  - What Will It Take to Move the Needle on Hospital Readmissions?

PMID- 24101683
TI  - Effectiveness and cost of failure mode and effects analysis methodology to reduce
      neurosurgical site infections.
AB  - Mercy Hospital Springfield is a tertiary care facility with 32 000 discharges and
      15 000 inpatient surgeries in 2011. From June 2009 through January 2011, a stable
      inpatient elective neurosurgery infection rate of 2.15% was observed. The failure
      mode and effects analysis (FMEA) methodology to reduce inpatient neurosurgery
      infections was utilized. Following FMEA implementation, overall elective
      neurosurgery infection rates were reduced to 1.51% and sustained through May
      2012. Compared with baseline, the post-FMEA deep-space and organ infection rate
      was reduced by 41% (P = .052). Overall hospital inpatient clean surgery infection
      rates for the same time frame did not decrease to the same extent, suggesting a
      specific effect of the FMEA. The study team believes that the FMEA interventions
      resulted in 14 fewer expected infections, $270 270 in savings, a 168-day
      reduction in expected length of stay, and 22 fewer readmissions. Given the
      serious morbidity and cost of health care-associated infections, the study team
      concludes that FMEA implementation was clinically cost-effective. 

PMID- 24101684
TI  - Amyloid-beta load predicts medial temporal lobe dysfunction in Alzheimer
      dementia.
AB  - Amyloid-beta (Abeta) deposition is a pathologic hallmark of Alzheimer disease
      (AD). Although the typical spatial distribution pattern of Abeta deposition in
      early AD mainly involves regions distant from the hippocampus, the predominant
      clinical feature is impairment of hippocampus-dependent memory. We aimed at
      elucidating the relationship between neocortical Abeta load, regional neuronal
      function, and memory impairment. METHODS: Thirty patients with early AD underwent
      combined (11)C-Pittsburgh compound B ((11)C-PIB) and (18)F-FDG PET and memory
      assessments. Composite measures of hemispheric Abeta load were calculated by
      volume-weighted mean values of neocortical (11)C-PIB binding. Voxelwise (18)F-FDG
      uptake was used as a measure of regional glucose metabolism reflecting neuronal
      activity. We investigated the relationship between left- and right-hemispheric
      Abeta load and regional glucose metabolism (voxelwise analyses). In addition, we
      assessed the correlations of hemispheric Abeta load (region-of-interest-based
      analyses) and regional glucose metabolism (voxelwise analysis) with memory
      performance. Analyses were corrected for age and sex. RESULTS: Higher Abeta load
      in the left hemisphere was associated with reduced glucose metabolism of the left
      medial temporal lobe (MTL; r(2) = 0.38) and correlated with worse wordlist recall
      (r = -0.37; partial correlation controlled for sex and age). Furthermore,
      wordlist recall correlated with regional glucose metabolism in the bilateral MTL
      and precuneus-posterior cingulate cortex and right lingual gyrus (r(2) = 0.24).
      CONCLUSION: We demonstrated an association between the left-hemispheric Abeta
      load and impairment of the left MTL in AD at 2 different levels: regional
      hypometabolism and verbal memory. This correlation suggests that neocortical
      amyloid deposition is connected to or even drives neuronal dysfunction and
      neurodegeneration of the MTL, which is associated with impaired episodic memory
      processing as a clinical core symptom of AD.

PMID- 24101685
TI  - Long-term outcome and toxicity after dose-intensified treatment with 131I-MIBG
      for advanced metastatic carcinoid tumors.
AB  - Reported experience with systemic (131)I-metaiodobenzylguanidine ((131)I-MIBG)
      therapy of neuroendocrine tumors comprises different dosing schemes. The aim of
      this study was to assess the long-term outcome and toxicity of treatment with
      11.1 GBq (300 mCi) of (131)I-MIBG per cycle. METHODS: We performed a
      retrospective review of 31 patients with advanced metastatic neuroendocrine
      tumors (20 with carcinoid tumors and 11 with other tumors) treated with (131)I
      MIBG. Treatment outcome was analyzed for patients with carcinoid tumors (the most
      common tumors in this study), and toxicity was analyzed for the entire patient
      cohort (n = 31). Treatment comprised 11.1 GBq (300 mCi) per course and minimum
      intervals of 3 mo. The radiographic response was classified according to modified
      Response Evaluation Criteria in Solid Tumors. Toxicity was determined according
      to Common Terminology Criteria for Adverse Events (version 3.0) for all
      laboratory data at regular follow-up visits and during outpatient care, including
      complete blood counts and hepatic and renal function tests. Survival analysis was
      performed with the Kaplan-Meier curve method (log rank test; P < 0.05). RESULTS:
      The radiographic responses in patients with carcinoid tumors comprised a minor
      response in 2 patients (10%), stable disease in 16 patients (80%; median time to
      progression, 34 mo), and progressive disease in 2 patients (10%). The symptomatic
      responses in patients with functioning carcinoid tumors comprised complete
      resolution in 3 of the 11 evaluable symptomatic patients (27%), partial
      resolution in 6 patients (55%), and no significant change in 11 patients. The
      median overall survival in patients with carcinoid tumors was 47 mo (95%
      confidence interval, 32-62), and the median progression-free survival was 34 mo
      (95% confidence interval, 13-55). Relevant treatment toxicities were confined to
      transient myelosuppression of grade 3 or 4 in 15.3% (leukopenia) and 7.6%
      (thrombocytopenia) of applied cycles and a suspected late adverse event (3% of
      patients), myelodysplastic syndrome, after a cumulative administered activity of
      66.6 GBq. The most frequent nonhematologic side effect was mild nausea (grade 1
      or 2), which was observed in 28% of administered cycles. No hepatic or renal
      toxicities were noted. CONCLUSION: Dose-intensified treatment with (131)I-MIBG at
      a fixed dose of 11.1 GBq (300 mCi) per cycle is safe and offers effective
      palliation of symptoms and disease stabilization in patients with advanced
      carcinoid tumors. The favorable survival and limited toxicity suggest that high
      cycle activities are suitable and that this modality may be used for targeted
      carcinoid treatment--either as an alternative or as an adjunct to other existing
      therapeutic options.

PMID- 24101686
TI  - Radiotracer imaging of peripheral vascular disease.
AB  - Peripheral vascular disease (PVD) is an atherosclerotic disease affecting the
      lower extremities, resulting in skeletal muscle ischemia, intermittent
      claudication, and, in more severe stages of disease, limb amputation and death.
      The evaluation of therapy in this patient population can be challenging, as the
      standard clinical indices are insensitive to assessment of regional alterations
      in skeletal muscle physiology. Radiotracer imaging of the lower extremities with
      techniques such as PET and SPECT can provide a noninvasive quantitative technique
      for the evaluation of the pathophysiology associated with PVD and may complement
      clinical indices and other imaging approaches. This review discusses the progress
      in radiotracer-based evaluation of PVD and highlights recent advancements in
      molecular imaging with potential for clinical application. 

PMID- 24101687
TI  - Addition of 18F-FDG PET/CT to clinical assessment predicts overall survival in
      HNSCC: a retrospective analysis with follow-up for 12 years.
AB  - (18)F-FDG PET/CT is used in the follow-up of patients with head and neck squamous
      cell cancer (HNSCC). However, its impact on clinical decision making and patient
      outcome is not fully established. The objective of this study was to determine
      the prognostic value of (18)F-FDG PET/CT for overall survival (OS) of HNSCC
      patients when performed in addition to clinical assessment between 4 and 24 mo
      after treatment. METHODS: This was a retrospective study at a single tertiary
      center. The institutional review board approved this study, and the requirement
      to obtain informed consent was waived. The study included 134 biopsy-proven HNSCC
      patients with 227 follow-up PET/CT scans. The primary outcome measure was OS.
      Median follow-up was 40 mo (range, 7-145 mo). Survival is presented as Kaplan
      Meier plots with Mantel-Cox log-rank test. The multivariate Cox model included
      clinical covariates. RESULTS: Of the 227 PET/CT scans, 41 (18%) were positive for
      tumor and 186 (82%) were negative for tumor. PET/CT identified recurrence in 5%
      (9/194) of scans performed without prior clinical concern and ruled out tumor in
      51.5% (17/33) of scans performed to evaluate clinical suspicion or uncertainty of
      recurrence. The median survival of PET-positive and -negative groups from the
      date of the scan was 20 and 30.5 mo, respectively (P < 0.0001). There was a
      significant difference in OS from the scan date between patients who had a
      positive PET/CT result for tumor and those who had a negative result (log-rank, P
      < 0.0001), with a hazard ratio of 29.74. Human papillomavirus status (P = 0.001)
      and PET/CT result (P = 0.04) were the only factors significantly associated with
      OS, adjusted for all other covariates. CONCLUSION: (18)F-FDG PET/CT performed
      between 4 and 24 mo after treatment adds value to clinical assessment at the time
      of the study, especially when there is clinical suspicion or uncertainty, and can
      serve as a prognostic marker of OS in HNSCC.

PMID- 24101688
TI  - Correlates of immune protection following cutaneous immunization with an
      attenuated Burkholderia pseudomallei vaccine.
AB  - Infections with the Gram-negative bacterium Burkholderia pseudomallei
      (melioidosis) are associated with high mortality, and there is currently no
      approved vaccine to prevent the development of melioidosis in humans. Infected
      patients also do not develop protective immunity to reinfection, and some
      individuals will develop chronic, subclinical infections with B. pseudomallei. At
      present, our understanding of what constitutes effective protective immunity
      against B. pseudomallei infection remains incomplete. Therefore, we conducted a
      study to elucidate immune correlates of vaccine-induced protective immunity
      against acute B. pseudomallei infection. BALB/c and C57BL/6 mice were immunized
      subcutaneously with a highly attenuated, Select Agent-excluded purM deletion
      mutant of B. pseudomallei (strain Bp82) and then subjected to intranasal
      challenge with virulent B. pseudomallei strain 1026b. Immunization with Bp82
      generated significant protection from challenge with B. pseudomallei, and
      protection was associated with a significant reduction in bacterial burden in
      lungs, liver, and spleen of immunized mice. Humoral immunity was critically
      important for vaccine-induced protection, as mice lacking B cells were not
      protected by immunization and serum from Bp82-vaccinated mice could transfer
      partial protection to nonvaccinated animals. In contrast, vaccine-induced
      protective immunity was found to be independent of both CD4 and CD8 T cells.
      Tracking studies demonstrated uptake of the Bp82 vaccine strain predominately by
      neutrophils in vaccine-draining lymph nodes and by smaller numbers of dendritic
      cells (DC) and monocytes. We concluded that protection following cutaneous
      immunization with a live attenuated Burkholderia vaccine strain was dependent
      primarily on generation of effective humoral immune responses. 

PMID- 24101689
TI  - Analysis of the proteome of intracellular Shigella flexneri reveals pathways
      important for intracellular growth.
AB  - Global proteomic analysis was performed with Shigella flexneri strain 2457T in
      association with three distinct growth environments: S. flexneri growing in broth
      (in vitro), S. flexneri growing within epithelial cell cytoplasm (intracellular),
      and S. flexneri that were cultured with, but did not invade, Henle cells
      (extracellular). Compared to in vitro and extracellular bacteria, intracellular
      bacteria had increased levels of proteins required for invasion and cell-to-cell
      spread, including Ipa, Mxi, and Ics proteins. Changes in metabolic pathways in
      response to the intracellular environment also were evident. There was an
      increase in glycogen biosynthesis enzymes, altered expression of sugar
      transporters, and a reduced amount of the carbon storage regulator CsrA. Mixed
      acid fermentation enzymes were highly expressed intracellularly, while
      tricarboxylic acid (TCA) cycle oxidoreductive enzymes and most electron transport
      chain proteins, except CydAB, were markedly decreased. This suggested that
      fermentation and the CydAB system primarily sustain energy generation
      intracellularly. Elevated levels of PntAB, which is responsible for NADPH
      regeneration, suggested a shortage of reducing factors for ATP synthesis. These
      metabolic changes likely reflect changes in available carbon sources, oxygen
      levels, and iron availability. Intracellular bacteria showed strong evidence of
      iron starvation. Iron acquisition systems (Iut, Sit, FhuA, and Feo) and the iron
      starvation, stress-associated Fe-S cluster assembly (Suf) protein were markedly
      increased in abundance. Mutational analysis confirmed that the mixed-acid
      fermentation pathway was required for wild-type intracellular growth and spread
      of S. flexneri. Thus, iron stress and changes in carbon metabolism may be key
      factors in the S. flexneri transition from the extra- to the intracellular
      milieu. 

PMID- 24101690
TI  - CD4+ T cells drive goblet cell depletion during Citrobacter rodentium infection.
AB  - Both idiopathic and infectious forms of colitis disrupt normal intestinal
      epithelial cell (IEC) proliferation and differentiation, although the mechanisms
      involved remain unclear. Recently, we demonstrated that infection by the
      attaching and effacing murine pathogen Citrobacter rodentium leads to a
      significant reduction in colonic goblet cell numbers (goblet cell depletion).
      This pathology depends on T and/or B cells, as Rag1(-/-) mice do not suffer this
      depletion during infection, instead suffering high mortality rates. To address
      the immune mechanisms involved, we reconstituted Rag(-/-) mice with either CD4(+)
      or CD8(+) T cells. Both T cell subsets increased Rag1(-/-) mouse survival during
      infection, with mice that received CD8(+) T cells developing colonic ulcers but
      not goblet cell depletion. In contrast, mice that received CD4(+) T cells showed
      goblet cell depletion in concert with exaggerated IEC proliferation. To define
      the possible involvement of T cell-derived cytokines, we infected gamma
      interferon receptor gene knockout (IFN-gammaR(-/-)) mice and wild-type mice given
      interleukin 17A (IL-17A) neutralizing antibodies and found that IFN-gamma
      signaling was required for both goblet cell depletion and increased IEC
      proliferation. Immunostaining revealed that C. rodentium cells preferentially
      localized to nonhyperplastic crypts containing numerous goblet cells, whereas
      hyperplastic, goblet cell-depleted crypts appeared protected from infection. To
      address whether goblet cell depletion benefits the C. rodentium-infected host, we
      increased goblet cell numbers using the gamma-secretase inhibitor dibenzazepine
      (DBZ), which resulted in greatly increased pathogen burdens and mortality rates.
      These results demonstrate that goblet cell depletion reflects host
      immunomodulation of IEC homeostasis and reflects a novel host defense mechanism
      against mucosal-adherent pathogens. 

PMID- 24101692
TI  - Exoenzyme S ADP-ribosylates Rab5 effector sites to uncouple intracellular
      trafficking.
AB  - Pseudomonas aeruginosa exoenzyme S (ExoS) ADP-ribosylates multiple eukaryotic
      targets to promote cytopathology and bacterial colonization. ADP-ribosylation of
      the small GTPase Rab5 has previously been shown to block fluid-phase endocytosis
      and trafficking of plasma membrane receptors to the early endosomes as well as
      inhibit phagocytosis of the bacterium. In this study, ExoS is shown to be capable
      of ADP-ribosylating 6 candidate arginine residues that are located in the
      effector binding region or in the C terminus of Rab5. Two Rab5 derivatives were
      engineered, which contained Arg->Ala mutations at four Arg residues within the
      effector binding region (EF) or two Arg residues within the C-terminal tail (TL).
      Expression of Rab5(TL) does not affect the ability of ExoS to modify
      intracellular trafficking, while expression of Rab5(EF) rescued the ability of
      ExoS to inhibit intracellular trafficking. ADP-ribosylation of effector arginines
      likely uncouples Rab5 signaling to downstream effectors. This is a different
      mechanism for inhibition than observed for the ADP-ribosylation of Ras by ExoS,
      where ADP-ribosylated Ras loses the ability to bind guanine nucleotide exchange
      factor (GEF). Other experiments showed that expression of dominant negative
      Rab5(Ser34Asn) does not inhibit ExoS trafficking to the perinuclear region of
      intoxicated cells. This study provides insight into a mechanism for how ExoS ADP
      ribosylation of Rab5 inhibits Rab5 function. 

PMID- 24101691
TI  - IL-27 receptor signaling regulates memory CD4+ T cell populations and suppresses
      rapid inflammatory responses during secondary malaria infection.
AB  - Interleukin-27 (IL-27) is known to control primary CD4(+) T cell responses during
      a variety of different infections, but its role in regulating memory CD4(+) T
      responses has not been investigated in any model. In this study, we have examined
      the functional importance of IL-27 receptor (IL-27R) signaling in regulating the
      formation and maintenance of memory CD4(+) T cells following malaria infection
      and in controlling their subsequent reactivation during secondary parasite
      challenge. We demonstrate that although the primary effector/memory CD4(+) T cell
      response was greater in IL-27R-deficient (WSX-1(-/-)) mice following Plasmodium
      berghei NK65 infection than in wild-type (WT) mice, there were no significant
      differences in the size of the maintained memory CD4(+) T population(s) at 20
      weeks postinfection in the spleen, liver, or bone marrow of WSX-1(-/-) mice
      compared with WT mice. However, the composition of the memory CD4(+) T cell pool
      was slightly altered in WSX-1(-/-) mice following clearance of primary malaria
      infection, with elevated numbers of late effector memory CD4(+) T cells in the
      spleen and liver and increased production of IL-2 in the spleen. Crucially, WSX
      1(-/-) mice displayed significantly enhanced parasite control compared with WT
      mice following rechallenge with homologous malaria parasites. Improved parasite
      control in WSX-1(-/-) mice during secondary infection was associated with
      elevated systemic production of multiple inflammatory innate and adaptive
      cytokines and extremely rapid proliferation of antigen-experienced T cells in the
      liver. These data are the first to demonstrate that IL-27R signaling plays a role
      in regulating the magnitude and quality of secondary immune responses during
      rechallenge infections. 

PMID- 24101693
TI  - Contribution of six flagellin genes to the flagellum biogenesis of Vibrio
      vulnificus and in vivo invasion.
AB  - Vibrio vulnificus is a halophilic pathogenic bacterium that is motile due to the
      presence of a single polar flagellum. V. vulnificus possesses a total of six
      flagellin genes organized into two loci (flaFBA and flaCDE). We proved that all
      six of the flagellin genes were transcribed, whereas only five (FlaA, -B, -C, -D,
      and -F) of the six flagellin proteins were detected. To understand roles of the
      six V. vulnificus flagellins in motility and virulence, mutants with single and
      multiple flagellin deletions were constructed. Mutations in flaB or flaC or the
      flaCDE locus resulted in a significant decrease in motility, adhesion, and
      cytotoxicity, whereas single mutations in the other flagellin genes or the flaFBA
      locus showed little or no effect. The motility was completely abolished only in
      the mutant lacking all six flagellin genes (flaFBA flaCDE). Surprisingly, a
      double mutation of flaB and flaD, a gene sharing 99% identity with the flaB at
      the amino acid level, resulted in the largest decrease in motility, adhesion, and
      cytotoxicity except for the mutant in which all six genes were deleted (the hexa
      mutant). Additionally, the 50% lethal doses (LD50s) of the flaB flaD and the
      flaFBA flaCDE mutants increased 23- and 91-fold in a mouse model, respectively,
      and the in vitro and in vivo invasiveness of the mutants was significantly
      decreased compared to that of the wild type. Taken together, the multiple
      flagellin subunits differentially contribute to the flagellum biogenesis and the
      pathogenesis of V. vulnificus, and among the six flagellin genes, flaB, flaD, and
      flaC were the most influential components. 

PMID- 24101694
TI  - Presence of Arp specifically contributes to joint tissue edema associated with
      early-onset Lyme arthritis.
AB  - Antiserum to the Borrelia burgdorferi arthritis-related protein, Arp, has been
      shown to prevent or reduce arthritis in immunodeficient mice. To directly
      investigate the requirement for this lipoprotein in the generation of Lyme
      arthritis, we utilized targeted deletion to generate a B. burgdorferi clone that
      lacked only the arp gene locus. Infection of Lyme disease-susceptible C3H/HeN
      mice with the arp deletion mutant demonstrated significantly reduced tibiotarsal
      joint swelling during the first 6 weeks of infection compared to a wild-type
      control. The severity of joint swelling was restored to wild-type levels in mice
      infected with an arp mutant clone complemented in cis. Interestingly, the reduced
      swelling of joint tissues exhibited by mice infected with the arp deletion mutant
      did not directly correspond to reduced underlying arthritis. Histopathology data
      at 2 weeks postinfection showed some reduction in arthritis severity caused by
      the arp mutant clone; however, by 8 weeks, no significant difference was observed
      between joint tissues infected by the wild-type or arp mutant clones. The
      spirochete load in the joint tissues of mice infected with the arp mutant was
      found to be greater than that exhibited by the wild-type control. Our findings
      demonstrate that this lipoprotein contributes to the generation of early-onset
      joint swelling and suggests that arp expression has a negative secondary effect
      on total spirochete numbers in joint tissues. 

PMID- 24101695
TI  - Association of obstructive sleep apnea and glucose metabolism in subjects with or
      without obesity.
AB  - OBJECTIVE: The purpose of this study was to investigate whether the impact of
      obstructive sleep apnea (OSA) on glucose metabolism was different according to
      the presence or absence of obesity. RESEARCH DESIGN AND METHODS: A total of 1,344
      subjects >40 years old from the Korean Genome and Epidemiology Study were
      included. OSA was detected by home portable sleep monitoring. Plasma glucose,
      HbA1c, and insulin resistance were compared according to OSA and obesity status.
      The associations between OSA and impaired fasting glucose (IFG), impaired glucose
      tolerance (IGT), IFG + IGT, and diabetes were evaluated in subjects with and
      without obesity after adjusting for several confounding variables. The effect of
      visceral obesity on this association was evaluated in 820 subjects who underwent
      abdominal computed tomography scanning. RESULTS: In subjects without obesity,
      fasting glucose, 2-h glucose after 75-g glucose loading, and HbA1c were higher in
      those with OSA than in those without after controlling for age, sex, and BMI. In
      addition, the presence of OSA in nonobese subjects was associated with a higher
      prevalence of IFG + IGT and diabetes after adjusting for several confounding
      variables (odds ratio 3.15 [95% CI 1.44-6.90] and 2.24 [1.43-3.50] for IFG + IGT
      and diabetes, respectively). Further adjustment for visceral fat area did not
      modify this association. In contrast, in those with obesity, none of the abnormal
      glucose tolerance categories were associated with OSA. CONCLUSIONS: The presence
      of OSA in nonobese individuals is significantly associated with impaired glucose
      metabolism, which can be responsible for future risk for diabetes and
      cardiovascular disease.

PMID- 24101696
TI  - Identification of factors associated with sural nerve regeneration and
      degeneration in diabetic neuropathy.
AB  - OBJECTIVE: Patients with diabetic neuropathy (DN) demonstrate variable degrees of
      nerve regeneration and degeneration. Our aim was to identify risk factors
      associated with sural nerve degeneration in patients with DN. RESEARCH DESIGN AND
      METHODS: Demographic, anthropometric, biochemical, and anatomical data of
      subjects with DN from a 52-week trial of acetyl-L-carnitine were retrospectively
      examined. Based on the change in sural nerve myelinated fiber density
      (DeltaMFD%), subjects were divided into three groups: regenerator (top 16
      percentiles, n = 67), degenerator (bottom 16 percentiles, n = 67), and
      intermediate (n = 290), with dramatically increased, decreased, and steady
      DeltaMFD%, respectively. ANOVA, Fisher exact test, and multifactorial logistic
      regression were used to evaluate statistical significance. RESULTS: DeltaMFD%s
      were 35.6 +/- 17.4 (regenerator), -4.8 +/- 12.1 (intermediate), and -39.8 +/-
      11.0 (degenerator). HbA1c at baseline was the only factor significantly different
      across the three groups (P = 0.01). In multifactorial logistic regression, HbA1c
      at baseline was also the only risk factor significantly different between
      regenerator (8.3 +/- 1.6%) and degenerator (9.2 +/- 1.8%) (odds ratio 0.68 [95%
      CI 0.54-0.85]; P < 0.01). Support Vector Machine classifier using HbA1c
      demonstrated 62.4% accuracy of classifying subjects into regenerator or
      degenerator. A preliminary microarray experiment revealed that upregulated genes
      in the regenerator group are enriched with cell cycle and myelin sheath
      functions, while downregulated genes are enriched in immune/inflammatory
      responses. CONCLUSIONS: These data, based on the largest cohort with DeltaMFD%
      information, suggest that HbA1c levels predict myelinated nerve fiber
      regeneration and degeneration in patients with DN. Therefore, maintaining optimal
      blood glucose control is likely essential in patients with DN to prevent
      continued nerve injury.

PMID- 24101697
TI  - Cardiovascular risk factors are associated with increased arterial stiffness in
      youth with type 1 diabetes: the SEARCH CVD study.
AB  - OBJECTIVE: To evaluate if presence of cardiovascular (CV) risk factors and their
      clustering as metabolic syndrome (MetS) is associated with increased arterial
      stiffness and accelerated progression over time among youth with type 1 diabetes.
      RESEARCH DESIGN AND METHODS: Longitudinal study of 298 youth with type 1 diabetes
      (age 14.5 years; 46.3% female; duration 4.8 years), with two research visits
      conducted 5 years apart. CV factors included: waist circumference, blood pressure
      (BP), fasting lipids (HDL cholesterol, LDL cholesterol [LDL-c], triglycerides),
      albumin/creatinine ratio, and HbA1c. MetS was based on Adult Treatment Panel III
      criteria modified for youth. Pulse wave velocity (PWV) in the carotid-femoral
      segment was measured by tonometry. Mixed models were used to assess the rate of
      progression in PWV and the association between CV factors and PWV over time.
      RESULTS: PWV increased significantly over time (0.145 m/s/year; P < 0.0001). MetS
      (P = 0.0035), large waist (P < 0.0001), and elevated BP (P = 0.0003) at baseline
      were each associated with worse PWV over time. These baseline factors, however,
      did not significantly influence the rate of progression. Increases in waist
      circumference (P < 0.0001), LDL-c levels (P = 0.0156), and declining glucose
      control (HbA1c; P = 0.0419) were independently associated with higher PWV over
      time. CONCLUSIONS: Presence, clustering, and worsening of CV risk factors are
      associated with increased arterial stiffness over time in youth with type 1
      diabetes. Whether improvement in CV risk factors early in life will slow the
      progression of arterial stiffness and reduce the burden of CV disease in this
      population requires further study.

PMID- 24101698
TI  - Enhancement of vasoreactivity and cognition by intranasal insulin in type 2
      diabetes.
AB  - OBJECTIVE: To determine acute effects of intranasal insulin on regional cerebral
      perfusion and cognition in older adults with type 2 diabetes mellitus (DM).
      RESEARCH DESIGN AND METHODS: This was a proof-of-concept, randomized, double
      blind, placebo-controlled intervention evaluating the effects of a single 40-IU
      dose of insulin or saline on vasoreactivity and cognition in 15 DM and 14 control
      subjects. Measurements included regional perfusion, vasodilatation to hypercapnia
      with 3-Tesla MRI, and neuropsychological evaluation. RESULTS: Intranasal insulin
      administration was well tolerated and did not affect systemic glucose levels. No
      serious adverse events were reported. Across all subjects, intranasal insulin
      improved visuospatial memory (P <= 0.05). In the DM group, an increase of
      perfusion after insulin administration was greater in the insular cortex compared
      with the control group (P = 0.0003). Cognitive performance after insulin
      administration was related to regional vasoreactivity. Improvements of
      visuospatial memory after insulin administration in the DM group (R(2)adjusted =
      0.44, P = 0.0098) and in the verbal fluency test in the control group
      (R(2)adjusted = 0.64, P = 0.0087) were correlated with vasodilatation in the
      middle cerebral artery territory. CONCLUSIONS: Intranasal insulin administration
      appears safe, does not affect systemic glucose control, and may provide acute
      improvements of cognitive function in patients with type 2 DM, potentially
      through vasoreactivity mechanisms. Intranasal insulin-induced changes in
      cognitive function may be related to vasodilatation in the anterior brain
      regions, such as insular cortex that regulates attention-related task
      performance. Larger studies are warranted to identify long-term effects and
      predictors of positive cognitive response to intranasal insulin therapy.

PMID- 24101699
TI  - Association of PAI-1 and fibrinogen with diabetic retinopathy in the Veterans
      Affairs Diabetes Trial (VADT).
AB  - OBJECTIVE: To test the hypothesis that high levels of plasminogen-activating
      inhibitor (PAI)-1 and fibrinogen at baseline were associated with the onset or
      progression of diabetic retinopathy (DR) during the Veterans Affairs Diabetes
      Trial (VADT). RESEARCH DESIGN AND METHODS: The VADT was an open-label,
      prospective, randomized controlled trial to test the effect of standard glycemic
      control (STD) compared with intensive control (INT) on cardiovascular events in
      patients with advanced type 2 diabetes mellitus (T2DM). Diabetic retinopathy (DR)
      outcomes were also collected. Incidence and progression of DR were assessed by
      grading seven-field stereoscopic fundus photographs at baseline and 5 years later
      taken in 858 of a total of 1,791 participants who completed both eye
      examinations. RESULTS: Assignment to INT was not independently associated with
      decreased risk of onset of DR. However, after adjustment for multiple covariates,
      baseline level of PAI-1 was an independent risk factor for the onset of DR. The
      risk for incidence of DR increased by 12% for each 10 ng/dL increase in baseline
      PAI-1 concentration (odds ratio [OR] 1.012 [95% CI 1.00-1.024], P = 0.042).
      Assignment to INT was not independently associated with decreased risk of
      progression of DR. However, there was an interaction between glycemic treatment
      assignment and fibrinogen level at baseline. INT was associated with decreased
      progression of retinopathy in those with fibrinogen <296 mg/dL (OR 0.55 [95% CI
      0.31-1.00], P = 0.03). CONCLUSIONS: The results require confirmation but are
      consistent with greater hypercoagulabilty and inflammation, as measured by higher
      levels of PAI-1 and fibrinogen, being related to DR and responsiveness to INT.

PMID- 24101701
TI  - Association of obstructive sleep apnea in rapid eye movement sleep with reduced
      glycemic control in type 2 diabetes: therapeutic implications.
AB  - OBJECTIVE: Severity of obstructive sleep apnea (OSA) has been associated with
      poorer glycemic control in type 2 diabetes. It is not known whether obstructive
      events during rapid eye movement (REM) sleep have a different metabolic impact
      compared with those during non-REM (NREM) sleep. Treatment of OSA is often
      limited to the first half of the night, when NREM rather than REM sleep
      predominates. We aimed to quantify the impact of OSA in REM versus NREM sleep on
      hemoglobin A1c (HbA1c) in subjects with type 2 diabetes. RESEARCH DESIGN AND
      METHODS: All participants underwent polysomnography, and glycemic control was
      assessed by HbA1c. RESULTS: Our analytic cohort included 115 subjects (65 women;
      age 55.2 +/- 9.8 years; BMI 34.5 +/- 7.5 kg/m(2)). In a multivariate linear
      regression model, REM apnea-hypopnea index (AHI) was independently associated
      with increasing levels of HbA1c (P = 0.008). In contrast, NREM AHI was not
      associated with HbA1c (P = 0.762). The mean adjusted HbA1c increased from 6.3% in
      subjects in the lowest quartile of REM AHI to 7.3% in subjects in the highest
      quartile of REM AHI (P = 0.044 for linear trend). Our model predicts that 4 h of
      continuous positive airway pressure (CPAP) use would leave 60% of REM sleep
      untreated and would be associated with a decrease in HbA1c by approximately
      0.25%. In contrast, 7 h of CPAP use would cover more than 85% of REM sleep and
      would be associated with a decrease in HbA1c by as much as 1%. CONCLUSIONS: In
      type 2 diabetes, OSA during REM sleep may influence long-term glycemic control.
      The metabolic benefits of CPAP therapy may not be achieved with the typical
      adherence of 4 h per night.

PMID- 24101702
TI  - Cardiac troponin I, cardiac troponin-specific autoantibodies and natriuretic
      peptides in children with hypoplastic left heart syndrome.
AB  - OBJECTIVES: To evaluate serum levels of cardiac troponin I (cTnI), autoantibodies
      against cardiac troponin (cTnAAbs) and natriuretic peptides during the treatment
      protocol in children with hypoplastic left heart syndrome (HLHS). METHODS: In a
      prospective study, we had 18 consecutive children with HLHS, for whom serum
      samples were analysed before the Norwood operation, before the bidirectional
      Glenn (BDG) operation, at the age of one year and before total cavo-pulmonary
      connection (TCPC). In addition, we performed a cross-sectional study in 22
      children examined before TCPC. Controls comprised 34 healthy children. RESULTS:
      In the prospective study, troponin I was positive in eight children before the
      Norwood operation. At the next follow-up, six children were positive. Thereafter,
      in all samples, cTnI was negative. Serum levels of natriuretic peptides decreased
      during the treatment protocol but remained higher than in controls throughout the
      study. In the cross-sectional study, cTnI levels were negative, but levels of
      natriuretic peptides were higher than in controls. Levels of cTnI and natriuretic
      peptides showed no correlation with oxygen saturation or haemoglobin
      concentration. Autoantibodies against cardiac troponin appeared in one patient
      but not in the control children. CONCLUSIONS: Cardiac TnI release is common
      before Norwood and BDG operations; then during the treatment protocol for HLHS,
      cTnI release resolves and serum levels of natriuretic peptides decrease. This may
      reflect a reduction of volume overload of the right ventricle during the surgical
      programme.

PMID- 24101704
TI  - Religion and medicine, again: JHMAS commentary on "The Lourdes medical cures
      revisited".

PMID- 24101703
TI  - Effect of gestational age on mRNA and protein expression of polyspecific organic
      cation transporters during pregnancy.
AB  - Polyspecific organic cation (OC) transporters play important roles in the
      disposition of clinically used drugs, including drugs used during pregnancy.
      Pregnancy is known to alter the expression of drug-metabolizing enzymes and
      transporters, but its specific effect on OC transporters has not been well
      defined. Using quantitative polymerase chain reaction and liquid chromatography
      coupled with tandem mass spectrometry targeted proteomics, we determined the
      effect of pregnancy and gestational age on mRNA and protein expression of major
      OC transporters in the kidney, liver, and placenta in mice with timed
      pregnancies. Human organic cation transporter 3 (hOCT3) expression was further
      investigated in human placentas from the first and second trimesters and at term.
      Our results showed that pregnancy had a marginal effect on renal mouse organic
      cation transporter 1/2 (mOct1/2) expression but significantly reduced mouse
      multidrug and toxin extrusion transporter 1 (mMate1) expression by 20%-40%.
      Hepatic expression of mOct1 and mMate1 was minimally affected by pregnancy. Human
      and mouse placentas predominantly expressed OCT3 with little expression of
      OCT1/2, MATE1/2, and plasma membrane monoamine transporter (PMAT). The hOCT3
      protein in first and second trimester and term placentas was quantified to be
      0.23 +/- 0.033, 0.38 +/- 0.072, and 0.36 +/- 0.099 fmol/MUg membrane protein,
      respectively. In contrast with the moderate increase in hOCT3 protein during
      human pregnancy, mOct3 expression in the mouse placenta was highly dependent on
      gestational age. Compared with gestational day (gd) 10, placental mOct3 mRNA
      increased by 37-fold and 46-fold at gd 15 and 19, leading to a 56-fold and 128
      fold increase in mOct3 protein, respectively. Our study provides new insights
      into the effect of pregnancy on the expression of polyspecific OC transporters
      and supports an important role of OCT3 in OC transport at the placental barrier. 

PMID- 24101705
TI  - On the edge of the film... Chilaiditi's sign.

PMID- 24101706
TI  - Relation between serum total bilirubin levels and severity of coronary artery
      disease in patients with non-ST-segment elevation myocardial infarction.
AB  - We studied 403 consecutive patients with non-ST-segment elevation myocardial
      infarction (NSTEMI). This population was divided into tertiles according to the
      SYNTAX score (SXscore). The high SXscore group was defined as an SXscore >=13,
      and the low SXscore group as an SXscore <13. The total bilirubin (sTB) and direct
      bilirubin levels of patients were significantly higher in the high SXscore group
      (P = .001 and P = .007, respectively). There was a correlation between sTB and
      SXscore (r = .495; P = .005). On multivariate linear regression analyses, age
      (beta = .100; P = .041), sTB levels (beta = .171; P = .005), low-density
      lipoprotein cholesterol (beta = .121; P = .014), and troponin-I (beta = .124; P =
      .011) remained independent correlates of high SXscore. The mean follow-up period
      was 18.2 months. All-cause mortality rate was higher in the high SXscore group
      but did not reach significance (P = .058). In conclusion, high sTB level is
      independently associated with severity of coronary artery disease in patients
      with NSTEMI. However, no association was found with long-term mortality. 

PMID- 24101707
TI  - Antiplatelet treatment and prothrombotic diathesis following endovascular
      abdominal aortic aneurysm repair.
AB  - Prothrombotic diathesis expressed by elevated levels of coagulation-specific
      biomarkers has been reported in patients with abdominal aortic aneurysm (AAA) and
      after AAA endovascular repair (EVAR). This study investigates the effect of
      antiplatelet agents (APLs) on the prothrombotic diathesis in the post-EVAR
      period. Forty elective EVAR patients had thrombin-antithrombin complex, d-dimer,
      fibrinopeptide A, and high-sensitivity C-reactive protein measured before, at 24
      hours, 1 month, and 6 months after EVAR. Patients receiving APLs postoperatively
      were compared with those not receiving APLs. All biomarkers were above the normal
      limits preoperatively and increased significantly 24 hours postoperatively
      followed by a drop at 1 and 6 months. No statistically significant changes were
      noted among patients receiving APLs in comparison with those not receiving APLs.
      The preoperative and postoperative prothrombotic diathesis of AAA following EVAR
      was confirmed in line with other reports. There was however no significant
      alteration of the examined biomarkers in patients receiving APLs. 

PMID- 24101700
TI  - Incidence of stroke according to presence of diabetic nephropathy and severe
      diabetic retinopathy in patients with type 1 diabetes.
AB  - OBJECTIVE: Type 1 diabetes is associated with a markedly increased risk of
      stroke, but only a few studies on the incidence of stroke in type 1 diabetes
      exist. Therefore, we assessed the incidence of stroke in patients with type 1
      diabetes and studied the impact of diabetic nephropathy (DN) and severe diabetic
      retinopathy (SDR) on this risk. RESEARCH DESIGN AND METHODS: We studied 4,083
      patients with type 1 diabetes from the Finnish Diabetic Nephropathy Study. Mean
      age was 37.4 +/- 11.8 years, duration of diabetes was 21.6 +/- 12.1 years, and
      52% were men. Strokes were identified from medical records, death certificates,
      and the National Hospital Discharge Register and classified based on medical
      files and brain images. RESULTS: During 36,680 person-years of follow-up, 149
      (4%) patients suffered an incident stroke (105 infarctions and 44 hemorrhages).
      Of the infarctions, 58 (55%) were lacunar. The incidence of stroke, cerebral
      infarction, and cerebral hemorrhage was 406 (95% CI 344-477), 286 (234-347), and
      120 (87-161) per 100,000 person-years, respectively. In an adjusted analysis,
      microalbuminuria increased the risk of stroke with a hazard ratio (HR) of 3.2
      (1.9-5.6), macroalbuminuria 4.9 (2.9-8.2), and end-stage renal disease 7.5 (4.2
      13.3), and SDR increased the risk with an HR of 3.0 (1.9-4.5). The risk of
      cerebral infarction, cerebral hemorrhage, and lacunar infarction increased in a
      similar manner. The proportion of lacunar versus nonlacunar infarction did not
      change across DN groups. CONCLUSIONS: The presence of SDR and DN, independently,
      increases the risk of stroke, cerebral infarction, and cerebral hemorrhage in
      patients with type 1 diabetes.

PMID- 24101708
TI  - Response to letter to the editor: mean platelet volume and platelet count values
      in patients with carbon monoxide poisoning.

PMID- 24101709
TI  - Anxiety score as a risk factor for radial artery vasospasm during radial
      interventions: a pilot study.

PMID- 24101710
TI  - Open repair versus endovascular stent graft repair of abdominal aortic aneurysms:
      do we need more randomized clinical trials?

PMID- 24101711
TI  - Association between serum cystatin C levels and coronary slow flow.
AB  - We assessed the association between serum cystatin C (CysC) levels and coronary
      slow flow (CSF) phenomenon in patients who underwent coronary angiography. A
      total of 210 patients (mean age 55.6 +/- 10.9 years; 100 females) were included.
      Patients were divided into 3 groups, (patients with CSF [group 2], with coronary
      artery disease [CAD; group 3], and without CAD [group 1]). Serum CysC levels in
      patients with CSF were significantly lower than those with and without CAD (912.5
      +/- 135.6, 820.4 +/- 104.2, and 1343.4 +/- 236.6 ng/mL in groups 1, 2, and 3,
      respectively; P < .001). Serum CysC levels correlated with the number of vessels
      with CSF and mean corrected thrombolysis in myocardial infarction frame count
      (Spearman correlation coefficient [r s] = .192, P < .001 and r s = .261, P < .001
      respectively). In conclusion, patients with CSF have lower CysC levels; this
      could be a useful biomarker of CSF involvement in patients who undergo diagnostic
      coronary angiography. 

PMID- 24101712
TI  - Comparison of Cockcroft-Gault and modification of diet in renal disease formulas
      as predictors of cardiovascular outcomes in patients with myocardial infarction
      treated with primary percutaneous coronary intervention.
AB  - We prospectively assessed the value of estimated glomerular filtration rate
      (eGFR) by the Modification of Diet in Renal Disease (MDRD) and Cockcroft-Gault (C
      G) equations in predicting inhospital adverse outcomes after primary coronary
      intervention for acute ST-segment elevation myocardial infarction. We classified
      647 patients into 3 categories according to eGFR, <60, 60 to 90, and >90
      mL/min/1.73 m(2). The eGFRC-G classified 17 patients in the >90 mL/min/1.73 m(2)
      subgroup and 6 and 11 patients in the 60 to 90 and <60 mL/min/1.73 m(2)
      subgroups, respectively. In multivariate analysis, patients with eGFRC-G < 60
      mL/min/1.73 m(2) had 19.5-fold (95% confidence interval [CI] 1.55-178) higher
      mortality risk and 5.48-fold (95% CI 1.75-24.21) higher major adverse cardiac
      events risk compared to patients with eGFRC-G >90 mL/min/1.73 m(2) (P = .01 and P
      = .01, respectively); the eGFRMDRD was not predictive. Although the MDRD equation
      more accurately estimates GFR in certain populations, the CG formula may be a
      better predictor of adverse events. 

PMID- 24101713
TI  - Nicotinic acid: current status in lipid management and cardiovascular disease
      prevention.

PMID- 24101714
TI  - New ESC guidelines published on stable coronary artery disease.

PMID- 24101715
TI  - Group therapy for anxiety in children with autism spectrum disorder.
AB  - AIM: To investigate the acceptability and feasibility of adapted group therapy
      for anxiety in children with autism spectrum disorder in a pilot randomised
      controlled trial. METHOD: A total of 32 children aged 9-13 years were randomised
      to immediate or delayed therapy using the 'Exploring Feelings' manual (Attwood,
      2004). Child and parent groups were run in parallel, for seven weekly sessions,
      under the supervision of experienced psychologists. The primary blinded outcome
      measures addressed change in overall functioning and in severity of the primary
      anxiety diagnosis after 3 months. RESULTS: Children met diagnostic criteria for 1
      6 anxiety disorders (median 3). At end point, both parents and children in the
      immediate therapy group were more likely to report a reduction in anxiety
      symptoms. Fidelity of delivery of the group therapy was high, and attendance was
      91%. CONCLUSIONS: This pilot trial established that children and families were
      willing to be recruited and randomised, the outcome measures were acceptable, the
      format and content of the groups were feasible within UK child and adolescent
      mental health services, the intervention was appreciated by families and
      attrition was very small.

PMID- 24101716
TI  - The Autism MEAL Plan: a parent-training curriculum to manage eating aversions and
      low intake among children with autism.
AB  - Feeding problems represent a frequent concern reported by caregivers of children
      with autism spectrum disorders, and growing evidence suggests atypical patterns
      of intake may place this population at risk of nutritional and/or related medical
      issues, including chronic vitamin and mineral deficiencies, poor bone growth, and
      obesity. This combination of factors emphasizes a clear need to identify and
      disseminate evidence-based treatment of feeding problems associated with autism
      spectrum disorders. Behavioral intervention represents an effective treatment for
      chronic feeding concerns in this population; however, evidence has largely been
      established with trained therapists working in highly structured settings. This
      pilot study seeks to fill this gap in the literature by describing and evaluating
      the Autism MEAL Plan, a behaviorally based parent-training curriculum to address
      feeding problems associated with autism spectrum disorders. We assessed the
      feasibility of the intervention in terms of program content and study protocol
      (e.g. recruitment and retention of participants, assessment procedures), as well
      as efficacy in terms of changes in feeding behaviors. A total of 10 families
      participated in the treatment condition, and the program was evaluated using a
      waitlist control design (n = 9), representing the first randomized-control study
      of a feeding intervention in autism spectrum disorders. Results provide
      provisional support regarding the utility of the program, including high social
      validity, parent perception of effectiveness, and reduced levels of caregiver
      stress following intervention. Implications, limitations, and future directions
      for this line of research are discussed.

PMID- 24101717
TI  - Observational learning by individuals with autism: a review of teaching
      strategies.
AB  - Observational learning is the process used to explain the acquisition of novel
      behaviors or performance of previously acquired behaviors under novel conditions
      after observing the behavior of another person and the consequences that follow
      the behavior. Many learners with autism do not attend to environmental stimuli at
      a level sufficient to learn a range of prosocial behaviors through observation of
      others. Modeling, group or dyadic instruction, and explicit observation training
      can improve the extent to which individuals with autism learn through
      observation. This article reviews previous research that involved observational
      learning by individuals with autism and outlines future research that could
      benefit instructional practices. 

PMID- 24101718
TI  - Motor development in children at risk of autism: a follow-up study of infant
      siblings.
AB  - Recently, evidence of poor or atypical motor skills in autism spectrum disorder
      has led some to argue that motor impairment is a core feature of the condition.
      The current study uses a longitudinal prospective design to assess the
      development of motor skills of 20 children at increased risk of developing autism
      spectrum disorder, who were recruited and tested at 9 and 40 months of age, on
      the basis of having an older sibling diagnosed with the condition. All children
      completed a range of motor, face processing, IQ and diagnostic assessments at a
      follow-up visit (aged 5-7 years), providing a detailed profile of development in
      this group from a number of standardised, parental report and experimental
      measures. A higher proportion of children than expected demonstrated motor
      difficulties at the follow-up visit and those highlighted by parental report as
      having poor motor skills as infants and toddlers were also more likely to have
      lower face processing scores and elevated autism-related social symptoms at 5-7
      years, despite having similar IQ levels. These data lend support to the argument
      that early motor difficulties may be a risk factor for later motor impairment as
      well as differences in social communication and cognition, traits that are
      related to autism spectrum disorder. 

PMID- 24101719
TI  - A synthetic nanofibrillar matrix promotes in vitro hepatic differentiation of
      embryonic stem cells and induced pluripotent stem cells.
AB  - Embryonic stem (ES) cells recapitulate normal developmental processes and serve
      as an attractive source for routine access to a large number of cells for
      research and therapies. We previously reported that ES cells cultured on M15
      cells, or a synthesized basement membrane (sBM) substratum, efficiently
      differentiated into an endodermal fate and subsequently adopted fates of various
      digestive organs, such as the pancreas and liver. Here, we established a novel
      hepatic differentiation procedure using the synthetic nanofiber (sNF) as a cell
      culture scaffold. We first compared endoderm induction and hepatic
      differentiation between murine ES cells grown on sNF and several other substrata.
      The functional assays for hepatocytes reveal that the ES cells grown on sNF were
      directed into hepatic differentiation. To clarify the mechanisms for the
      promotion of ES cell differentiation in the sNF system, we focused on the
      function of Rac1, which is a Rho family member protein known to regulate the
      actin cytoskeleton. We observed the activation of Rac1 in undifferentiated and
      differentiated ES cells cultured on sNF plates, but not in those cultured on
      normal plastic plates. We also show that inhibition of Rac1 blocked the
      potentiating effects of sNF on endoderm and hepatic differentiation throughout
      the whole differentiation stages. Taken together, our results suggest that
      morphological changes result in cellular differentiation controlled by Rac1
      activation, and that motility is not only the consequence, but is also able to
      trigger differentiation. In conclusion, we believe that sNF is a promising
      material that might contribute to tissue engineering and drug delivery. 

PMID- 24101721
TI  - Tenascin-C and tenascin-W in whisker follicle stem cell niches: possible roles in
      regulating stem cell proliferation and migration.
AB  - The whisker follicle has CD34-positive stem cells that migrate from their niche
      near the bulge along the glassy membrane to the whisker bulb, where they
      participate in the formation of the whisker shaft. Using immunohistochemistry, we
      found the glycoprotein tenascin-C in the fibrous capsule of mouse whisker
      follicles, along the glassy membrane and in the trabecular region surrounding
      keratin-15-negative, CD34-positive stem cells. The related glycoprotein tenascin
      W is found in the CD34-positive stem cell niche, in nearby trabeculae and along
      the glassy membrane. Tenascin-W is also found in the neural stem cell niche of
      nearby hair follicles. The formation of stress fibers and focal adhesion
      complexes in CD34-positive whisker-derived stem cells cultured on fibronectin was
      inhibited by both tenascin-C and tenascin-W, which is consistent with a role for
      these glycoproteins in promoting the migration of these cells from the niche to
      the whisker bulb. Tenascin-C, but not tenascin-W, increased the proliferation of
      whisker follicle stem cells in vitro. Thus, the CD34-positive whisker follicle
      stem cell niche contains both tenascin-C and tenascin-W, and these glycoproteins
      might play a role in directing the migration and proliferation of these stem
      cells. 

PMID- 24101720
TI  - Etv5a regulates the proliferation of ventral mesoderm cells and the formation of
      hemato-vascular derivatives.
AB  - Hematopoietic and vascular endothelial cells constitute the circulatory system
      and are both generated from the ventral mesoderm. However, the molecules and
      signaling pathways involved in ventral mesoderm formation and specification
      remain unclear. We found that zebrafish etv5a was expressed in the ventral
      mesoderm during gastrulation. Knockdown of Etv5a using morpholinos increased the
      proliferation of ventral mesoderm cells and caused defects in hematopoietic
      derivatives and in vascular formation. By contrast, the formation of other
      mesodermal derivatives, such as pronephros, somites and the gut wall, was not
      affected. Knockdown specificity was further confirmed by overexpression of an
      etv5a construct lacking its acidic domain. In conclusion, our data reveal that
      etv5a is essential for the inhibition of ventral mesoderm cell proliferation and
      for the formation of the hemato-vascular lineage.

PMID- 24101722
TI  - The tubulin cofactor C family member TBCCD1 orchestrates cytoskeletal filament
      formation.
AB  - TBCCD1 is an enigmatic member of the tubulin-binding cofactor C (TBCC) family of
      proteins required for mother-daughter centriole linkage in the green alga
      Chlamydomonas reinhardtii and nucleus-centrosome-Golgi linkage in mammalian
      cells. Loss of these linkages has severe morphogenetic consequences, but the
      mechanism(s) through which TBCCD1 contributes to cell organisation is unknown. In
      the African sleeping sickness parasite Trypanosoma brucei a microtubule-dominant
      cytoskeleton dictates cell shape, influencing strongly the positioning and
      inheritance patterns of key intracellular organelles. Here, we show the
      trypanosome orthologue of TBCCD1 is found at multiple locations: centrioles, the
      centriole-associated Golgi 'bi-lobe', and the anterior end of the cell body. Loss
      of Trypanosoma brucei TBCCD1 results in disorganisation of the structurally
      complex bi-lobe architecture and loss of centriole linkage to the single unit
      copy mitochondrial genome (or kinetoplast) of the parasite. We therefore identify
      TBCCD1 as an essential protein associated with at least two filament-based
      structures in the trypanosome cytoskeleton. The last common ancestor of
      trypanosomes, animals and green algae was arguably the last common ancestor of
      all eukaryotes. On the basis of our observations, and interpretation of published
      data, we argue for an unexpected co-option of the TBCC domain for an essential
      non-tubulin-related function at an early point during evolution of the eukaryotic
      cytoskeleton. 

PMID- 24101723
TI  - Postnatal ablation of osteoblast Smad4 enhances proliferative responses to
      canonical Wnt signaling through interactions with beta-catenin.
AB  - Canonical Wnt (cWnt) signaling through beta-catenin regulates osteoblast
      proliferation and differentiation to enhance bone formation. We previously
      reported that osteogenic action of beta-catenin is dependent on BMP signaling.
      Here, we further examined interactions between cWnt and BMP in bone. In
      osteoprogenitors stimulated with BMP2, beta-catenin localizes to the nucleus,
      physically interacts with Smad4, and is recruited to DNA-binding transcription
      complexes containing Smad4, R-Smad1/5 and TCF4. Furthermore, Tcf/Lef-dependent
      transcription, Ccnd1 expression and proliferation all increase when Smad4, 1 or 5
      levels are low, whereas TCF/Lef activities decrease when Smad4 expression is
      high. The ability of Smad4 to antagonize transcription of Ccnd1 is dependent on
      DNA-binding activity but Smad4-dependent transcription is not required. In mice,
      conditional deletion of Smad4 in osterix(+) cells increases mitosis of cells on
      trabecular bone surfaces as well as in primary osteoblast cultures from adult
      bone marrow and neonatal calvaria. By contrast, ablation of Smad4 delays
      differentiation and matrix mineralization by primary osteoblasts in response to
      Wnt3a, indicating that loss of Smad4 perturbs the balance between proliferation
      and differentiation in osteoprogenitors. We propose that Smad4 and Tcf/Lef
      transcription complexes compete for beta-catenin, thus restraining cWnt-dependent
      proliferative signals while favoring the matrix synthesizing activity of
      osteoblasts.

PMID- 24101725
TI  - The cell-end marker TeaA and the microtubule polymerase AlpA contribute to
      microtubule guidance at the hyphal tip cortex of Aspergillus nidulans to provide
      polarity maintenance.
AB  - In the absence of landmark proteins, hyphae of Aspergillus nidulans lose their
      direction of growth and show a zigzag growth pattern. Here, we show that the cell
      end marker protein TeaA is important for localizing the growth machinery at
      hyphal tips. The central position of TeaA at the tip correlated with the
      convergence of the microtubule (MT) ends to a single point. Conversely, in the
      absence of TeaA, the MTs often failed to converge to a single point at the
      cortex. Further analysis suggested a functional connection between TeaA and AlpA
      (an ortholog of the MT polymerase Dis1/CKAP5/XMAP215) for proper regulation of MT
      growth at hyphal tips. AlpA localized at MT plus-ends, and bimolecular
      fluorescence complementation assays suggested that it interacted with TeaA after
      MT plus-ends reached the tip cortex. In vitro MT polymerization assays showed
      that AlpA promoted MT growth up to sevenfold. Addition of the C-terminal region
      of TeaA increased the catastrophe frequency of the MTs. Thus, the control of the
      AlpA activity through TeaA might be a novel principle for MT growth regulation
      after reaching the cortex. In addition, we present evidence that the curvature of
      hyphal tips also could be involved in the control of MT growth at hyphal tips.

PMID- 24101726
TI  - A double-negative feedback loop between Wnt-beta-catenin signaling and HNF4alpha
      regulates epithelial-mesenchymal transition in hepatocellular carcinoma.
AB  - Wnt-beta-catenin signaling participates in the epithelial-mesenchymal transition
      (EMT) in a variety of cancers; however, its involvement in hepatocellular
      carcinoma (HCC) and downstream molecular events is largely undefined. HNF4alpha
      is the most prominent and specific factor maintaining the differentiation of
      hepatic lineage cells and a potential EMT regulator in HCC cells. However, the
      molecular mechanisms by which HNF4alpha maintains the differentiated liver
      epithelium and inhibits EMT have not been completely defined. In this study, we
      systematically explored the relationship between Wnt-beta-catenin signaling and
      HNF4alpha in the EMT process of HCC cells. Our results indicated that HNF4alpha
      expression was negatively regulated during Wnt-beta-catenin signaling-induced EMT
      through Snail and Slug in HCC cells. In contrast, HNF4alpha was found to directly
      associate with TCF4 to compete with beta-catenin but facilitate transcription co
      repressor activities, thus inhibiting expression of EMT-related Wnt-beta-catenin
      targets. Moreover, HNF4alpha may control the switch between the transcriptional
      and adhesion functions of beta-catenin. Overexpression of HNF4alpha was found to
      completely compromise the Wnt-beta-catenin-signaling-induced EMT phenotype.
      Finally, we determined the regulation pattern between Wnt-beta-catenin signaling
      and HNF4alpha in rat tumor models. Our studies have identified a double-negative
      feedback mechanism controlling Wnt-beta-catenin signaling and HNF4alpha
      expression in vitro and in vivo, which sheds new light on the regulation of EMT
      in HCC. The modulation of these molecular processes may be a method of inhibiting
      HCC invasion by blocking Wnt-beta-catenin signaling or restoring HNF4alpha
      expression to prevent EMT.

PMID- 24101727
TI  - Regulation of endoplasmic reticulum Ca(2+) oscillations in mammalian eggs.
AB  - Changes in the intracellular concentration of free calcium ([Ca(2+)]i) regulate
      diverse cellular processes including fertilization. In mammalian eggs, the
      [Ca(2+)]i changes induced by the sperm unfold in a pattern of periodical rises,
      also known as [Ca(2+)]i oscillations. The source of Ca(2+) during oscillations is
      the endoplasmic reticulum ([Ca(2+)]ER), but it is presently unknown how
      [Ca(2+)]ER is regulated. Here, we show using mouse eggs that [Ca(2+)]i
      oscillations induced by a variety of agonists, including PLCzeta, SrCl2 and
      thimerosal, provoke simultaneous but opposite changes in [Ca(2+)]ER and cause
      differential effects on the refilling and overall load of [Ca(2+)]ER. We also
      found that Ca(2+) influx is required to refill [Ca(2+)]ER, because the loss of
      [Ca(2+)]ER was accelerated in medium devoid of Ca(2+). Pharmacological
      inactivation of the function of the mitochondria and of the Ca(2+)-ATPase pumps
      PMCA and SERCA altered the pattern of oscillations and abruptly reduced
      [Ca(2+)]ER, especially after inactivation of mitochondria and SERCA functions. We
      also examined the expression of SERCA2b protein and found that it was expressed
      throughout oocyte maturation and attained a conspicuous cortical cluster
      organization in mature eggs. We show that its overexpression reduces the duration
      of inositol-1,4,5-trisphosphate-induced [Ca(2+)]i rises, promotes initiation of
      oscillations and enhances refilling of [Ca(2+)]ER. Collectively, our results
      provide novel insights on the regulation of [Ca(2+)]ER oscillations, which
      underlie the unique Ca(2+)-signalling system that activates the developmental
      program in mammalian eggs.

PMID- 24101724
TI  - Dynamic mitochondrial-nuclear redistribution of the immunophilin FKBP51 is
      regulated by the PKA signaling pathway to control gene expression during
      adipocyte differentiation.
AB  - Glucocorticoids play an important role in adipogenesis through the glucocorticoid
      receptor (GR) that forms a heterocomplex with Hsp90*Hsp70 and one high molecular
      weight immunophilin, either FKBP51 or FKBP52. When 3T3-L1 preadipocytes are
      induced to differentiate, FKBP51 expression progressively increases, whereas
      FKBP52 decreases, and Hsp90, Hsp70, p23 and Cyp40 remain unchanged.
      Interestingly, FKBP51 rapidly translocates from mitochondria to the nucleus where
      it is retained upon its interaction with chromatin and the nuclear matrix. FKBP51
      nuclear localization is transient, and after 48 hours it cycles back to
      mitochondria. Importantly, this dynamic FKBP51 mitochondrial-nuclear shuttling
      depends on PKA signaling, because its inhibition by PKI or knockdown of PKA
      calpha by siRNA, prevented FKBP51 nuclear translocation induced by IBMX. In
      addition, the electrophoretic pattern of migration of FKBP51 is altered by
      treatment of cells with PKI or knockdown of PKA-calpha, suggesting that FKBP51 is
      a PKA substrate. In preadipocytes, FKBP51 colocalizes with PKA-calpha in
      mitochondria. When adipogenesis is triggered, PKA-calpha also moves to the
      nucleus colocalizing with FKBP51 mainly in the nuclear lamina. Moreover, FKBP51
      and GR interaction increases when preadipocytes are induced to differentiate. GR
      transcriptional capacity is reduced when cells are incubated in the presence of
      IBMX, forskolin or dibutyryl-cAMP, compounds that induced FKBP51 nuclear
      translocation, but not by a specific activator of EPAC. FKBP51 knockdown
      facilitates adipogenesis, whereas ectopic expression of FKBP51 blocks
      adipogenesis. These findings indicate that the dynamic mitochondrial-nuclear
      shuttling of FKBP51 regulated by PKA may be key in fine-tuning the
      transcriptional control of GR target genes required for the acquisition of
      adipocyte phenotype. 

PMID- 24101728
TI  - MicroRNA-141-3p plays a role in human mesenchymal stem cell aging by directly
      targeting ZMPSTE24.
AB  - Human mesenchymal stem cell (hMSC) aging may lead to a reduced tissue
      regeneration capacity and a decline in physiological functions. However, the
      molecular mechanisms controlling hMSC aging in the context of prelamin A
      accumulation are not completely understood. In this study, we demonstrate that
      the accumulation of prelamin A in the nuclear envelope results in cellular
      senescence and potential downstream regulatory mechanisms responsible for
      prelamin A accumulation in hMSCs. We show for the first time that ZMPSTE24, which
      is involved in the post-translational maturation of lamin A, is largely
      responsible for the prelamin A accumulation related to cellular senescence in
      hMSCs. Direct binding of miR-141-3p to the 3'UTR of ZMPSTE24 transcripts was
      confirmed using a 3'UTR-luciferase reporter assay. We also found that miR-141-3p,
      which is overexpressed during senescence as a result of epigenetic regulation, is
      able to decrease ZMPSTE24 expression levels, and leads to an upregulation of
      prelamin A in hMSCs. This study provides new insights into mechanisms regulating
      MSC aging and may have implications for therapeutic application to reduce age
      associated MSC pool exhaustion. 

PMID- 24101729
TI  - Signaling by Folded gastrulation is modulated by mitochondrial fusion and
      fission.
AB  - Mitochondria are increasingly being identified as integrators and regulators of
      cell signaling pathways. Folded gastrulation (Fog) is a secreted signaling
      molecule best known for its role in regulating cell shape change at the ventral
      furrow during gastrulation in Drosophila. Fog is thought to signal, through a G
      protein-coupled receptor, to effect downstream cytoskeletal changes necessary for
      cell shape change. However, the mechanisms regulating Fog signaling that lead to
      change in cell morphology are poorly understood. This study describes the
      identification of proteins involved in mitochondrial fusion and fission as
      regulators of Fog signaling. Pro-fission factors were found to function as
      enhancers of signaling, whereas pro-fusion factors were found to have the
      opposite effect. Consistent with this, activation of Fog signaling resulted in
      mitochondrial fragmentation, and inhibiting this process could attenuate Fog
      signaling. The findings presented here show that mitochondria, through regulation
      of fusion and fission, function as downstream effectors and modulators of Fog
      signaling and Fog-dependent cell shape change. 

PMID- 24101730
TI  - NCX3 regulates mitochondrial Ca(2+) handling through the AKAP121-anchored
      signaling complex and prevents hypoxia-induced neuronal death.
AB  - The mitochondrial influx and efflux of Ca(2+) play a relevant role in cytosolic
      and mitochondrial Ca(2+) homeostasis, and contribute to the regulation of
      mitochondrial functions in neurons. The mitochondrial Na(+)/Ca(2+) exchanger,
      which was first postulated in 1974, has been primarily investigated only from a
      functional point of view, and its identity and localization in the mitochondria
      have been a matter of debate over the past three decades. Recently, a Li(+)
      dependent Na(+)/Ca(2+) exchanger extruding Ca(2+) from the matrix has been found
      in the inner mitochondrial membrane of neuronal cells. However, evidence has been
      provided that the outer membrane is impermeable to Ca(2+) efflux into the
      cytoplasm. In this study, we demonstrate for the first time that the nuclear
      encoded NCX3 isoform (1) is located on the outer mitochondrial membrane (OMM) of
      neurons; (2) colocalizes and immunoprecipitates with AKAP121 (also known as
      AKAP1), a member of the protein kinase A anchoring proteins (AKAPs) present on
      the outer membrane; (3) extrudes Ca(2+) from mitochondria through AKAP121
      interaction in a PKA-mediated manner, both under normoxia and hypoxia; and (4)
      improves cell survival when it works in the Ca(2+) efflux mode at the level of
      the OMM. Collectively, these results suggest that, in neurons, NCX3 regulates
      mitochondrial Ca(2+) handling from the OMM through an AKAP121-anchored signaling
      complex, thus promoting cell survival during hypoxia.

PMID- 24101731
TI  - Human skeletal muscle fibroblasts, but not myogenic cells, readily undergo
      adipogenic differentiation.
AB  - We characterised the adherent cell types isolated from human skeletal muscle by
      enzymatic digestion, and demonstrated that even at 72 hours after isolation these
      cultures consisted predominantly of myogenic cells (CD56(+), desmin(+)) and
      fibroblasts (TE-7(+), collagen VI(+), PDGFRalpha(+), vimentin(+),
      fibronectin(+)). To evaluate the behaviour of the cell types obtained, we
      optimised a double immuno-magnetic cell-sorting method for the separation of
      myogenic cells from fibroblasts. This procedure gave purities of >96% for
      myogenic (CD56(+), desmin(+)) cells. The CD56(-) fraction obtained from the first
      sort was highly enriched in TE-7(+) fibroblasts. Using quantitative analysis of
      immunofluorescent staining for lipid content, lineage markers and transcription
      factors, we tested if the purified cell populations could differentiate into
      adipocytes in response to treatment with either fatty acids or adipocyte-inducing
      medium. Both treatments caused the fibroblasts to differentiate into adipocytes,
      as shown by loss of intracellular TE-7, upregulation of the adipogenic
      transcription factors PPARgamma and C/EBPalpha, and adoption of a lipid-laden
      adipocyte morphology. By contrast, myogenic cells did not undergo adipogenesis
      and showed differential regulation of PPARgamma and C/EBPalpha in response to
      these adipogenic treatments. Our results show that human skeletal muscle
      fibroblasts are at least bipotent progenitors that can remain as extracellular
      matrix-producing cells or differentiate into adipocytes.

PMID- 24101732
TI  - Prevalence of menstrual migraine: a population-based study.
AB  - AIM: To present data from a population-based epidemiological study on menstrual
      migraine. MATERIAL AND METHODS: Altogether, 5000 women aged 30-34 years were
      screened for menstrual migraine. Women with self-reported menstrual migraine in
      at least half of their menstrual cycles were invited to an interview and
      examination. We expanded the International Classification of Headache Disorders
      III beta appendix criteria on menstrual migraine to include both migraine without
      aura and migraine with aura, as well as probable menstrual migraine with aura and
      migraine without aura. RESULTS: A total of 237 women were included in the study.
      The prevalence among all women was as follows: any type of menstrual migraine
      7.6%; menstrual migraine without aura 6.1%; menstrual migraine with aura 0.6%;
      probable menstrual migraine without aura 0.6%; probable menstrual migraine with
      aura 0.3%. The corresponding figures among female migraineurs were: any type of
      menstrual migraine 22.0%, menstrual migraine without aura 17.6%, menstrual
      migraine with aura 1.7%, probable menstrual migraine without aura 1.6% and
      probable menstrual migraine with aura 1.0%. CONCLUSION: More than one of every
      five female migraineurs aged 30-34 years have migraine in >=50% of menstruations.
      The majority has menstrual migraine without aura and one of eight women had
      migraine with aura in relation to their menstruation. Our results indicate that
      the ICHD III beta appendix criteria of menstrual migraine are not exhaustive.

PMID- 24101733
TI  - Time for a paradigm shift with computerized adaptive testing of general physical
      function outcomes measurements.
AB  - BACKGROUND: Patient-reported outcomes (PRO) are critical to understanding the
      value of orthopedic treatments. We hypothesized that use of the computerized
      adaptive testing from a well-characterized physical function item bank would show
      superiority in assessing all levels of physical function compared to current
      standard generic physical function outcomes instruments for foot and ankle
      patients. METHODS: In a population of 126 foot and ankle patients we compared the
      psychometric properties for three PROs: the Physical Function subscale of the
      Medical Outcomes General Health Survey (SF-36 PF) version 2, the Patient-Reported
      Outcomes Measurement Information System (PROMIS) Physical Function (PF)
      Computerized Adaptive Test (CAT), and the Lower Extremity (LE) CAT. A Rasch item
      response theory (IRT) model was applied to assess and compare the fit,
      dimensionality, reliability, validity, and coverage. RESULTS: The unexplained
      variance for the PF CAT was 3.9% and the LE CAT was 2.1%, suggesting each
      instrument explained a single concept. The SF-36 PF had more concerning
      unexplained variance of 7.6%. We found no floor or ceiling effects for the PF
      CAT, a minimal floor effect (1.6%) but no ceiling effect for the LE CAT, and an
      11.1% floor effect and 9.5% ceiling effect for the SF-36 PF. CONCLUSION: Foot and
      ankle clinicians and researchers interested in measuring patient perceived
      functional outcomes with a generic instrument should consider using either the PF
      CAT or the LE CAT rather than the SF-36 PF. Further studies comparing these CATs
      to anatomic specific instruments are needed. LEVEL OF EVIDENCE: Level I,
      diagnostic study.

PMID- 24101734
TI  - Purinergic P2X7 receptors mediate cell death in mouse cerebellar astrocytes in
      culture.
AB  - The brain distribution and functional role of glial P2X7 receptors are broader
      and more complex than initially anticipated. We characterized P2X7 receptors from
      cerebellar astrocytes at the molecular, immunocytochemical, biophysical, and cell
      physiologic levels. Mouse cerebellar astrocytes in culture express mRNA coding
      for P2X7 receptors, which is translated into P2X7 receptor protein as proven by
      Western blot analysis and immunocytochemistry. Fura-2 imaging showed cytosolic
      calcium responses to ATP and the synthetic analog 3'-O-(4-benzoyl)benzoyl-ATP
      (BzATP) exhibited two components, namely an initial transient and metabotropic
      component followed by a sustained one that depended on extracellular calcium.
      This latter component, which was absent in astrocytes from P2X7 receptor knockout
      mice (P2X7 KO), was modulated by extracellular Mg(2+), and was sensitive to
      Brilliant Blue G (BBG) and 3-(5-(2,3-dichlorophenyl)-1H-tetrazol-1-yl)methyl
      pyridine (A438079) antagonism. BzATP also elicited inwardly directed
      nondesensitizing whole-cell ionic currents that were reduced by extracellular
      Mg(2+) and P2X7 antagonists (BBG and calmidazolium). In contrast to that
      previously reported in rat cerebellar astrocytes, sustained BzATP application
      induced a gradual increase in membrane permeability to large cations, such as N
      methyl-d-glucamine and 4-[3-methyl-2(3H)-benzoxazolylidene)-methyl]-1-[3
      (triethylammonio)propyl]diiodide, which ultimately led to the death of mouse
      astrocytes. Cerebellar astrocyte cell death was prevented by BBG but not by
      calmidazolium, removal of extracellular calcium, or treatment with the caspase-3
      inhibitor, benzyloxycarbonyl-Asp(OMe)-Glu(OMe)-Val-Asp(OMe)-fluoromethylketone,
      thus suggesting a necrotic-type mechanism of cell death. Since this cellular
      response was not observed in astrocytes from P2X7 KO mice, this study suggests
      that stimulation of P2X7 receptor may convey a cell death signal to cerebellar
      astrocytes in a species-specific manner.

PMID- 24101735
TI  - Analysis of histamine receptor knockout mice in models of inflammation.
AB  - The diverse functions of histamine are mediated by four specific histamine
      receptor subtypes, which belong to the family of G-protein-coupled receptors.
      Here, we summarize data obtained with histamine-deficient L-histidine
      decarboxylase knockout and histamine receptor subtype knockout mice in
      inflammation models. Advantages and disadvantages of the knockout approaches
      compared with pharmacologic approaches are discussed critically. Due to many
      controversial data it is very difficult to draw clear-cut conclusions from the
      data provided in the literature. Thus, the published studies highlight the
      complexity of histamine function in inflammation and the need for much more
      systematic experimental work.

PMID- 24101736
TI  - Detection of tumor progression in optic pathway glioma with and without
      neurofibromatosis type 1.
AB  - BACKGROUND: We wanted to determine the sensitivity and specificity of serial
      changes in visual acuity and visual evoked potentials (VEPs) to detect
      radiological progression of tumor volume in children with optic pathway gliomas.
      METHODS: From a retrospective review of a cohort of 69 patients, 54 patients met
      inclusion criteria (31 with primary chemotherapy, 4 with primary radiotherapy,
      and 19 with stable tumor volume and no treatment). Age at presentation ranged
      from 0.3 to 13 years. Patients were serially followed by MRI, age-corrected
      visual acuity in log minimum angle of resolution (logMAR), and pattern VEP.
      Longitudinal data averaged 7.9 years (range 0.5-16 y). Visual assessments were
      aligned with MRI data within 6-month intervals. Tumor progression was defined by
      25% or greater increase in volume. RESULTS: Visual acuity in the better eye had
      poor sensitivity and specificity for detecting tumor volume progression (0.5 and
      0.5, respectively). Visual acuity in the worse eye showed worse sensitivity and
      specificity because false positives (visual decline without tumor progression)
      were more frequent than true positives (visual decline with tumor progression).
      VEPs showed slightly better sensitivity and specificity (0.69 and 0.58,
      respectively). In patients with stable tumors, visual acuity fluctuated +/-0.55
      logMAR (SD = 0.15) between examinations. VEP amplitude fluctuated -0.74 to 0.48
      log units (SD = 0.19) between examinations. CONCLUSIONS: Serial changes in visual
      function do not reliably detect tumor progression. Conversely, tumor progression
      does not reliably indicate decreased visual function. Objective visual function
      and serial MRIs are complementary in management of optic pathway gliomas.

PMID- 24101737
TI  - Comparative drug pair screening across multiple glioblastoma cell lines reveals
      novel drug-drug interactions.
AB  - BACKGROUND: Glioblastoma multiforme (GBM) is the most aggressive brain tumor in
      adults, and despite state-of-the-art treatment, survival remains poor and novel
      therapeutics are sorely needed. The aim of the present study was to identify new
      synergistic drug pairs for GBM. In addition, we aimed to explore differences in
      drug-drug interactions across multiple GBM-derived cell cultures and predict such
      differences by use of transcriptional biomarkers. METHODS: We performed a screen
      in which we quantified drug-drug interactions for 465 drug pairs in each of the 5
      GBM cell lines U87MG, U343MG, U373MG, A172, and T98G. Selected interactions were
      further tested using isobole-based analysis and validated in 5 glioma-initiating
      cell cultures. Furthermore, drug interactions were predicted using microarray
      based transcriptional profiling in combination with statistical modeling.
      RESULTS: Of the 5 * 465 drug pairs, we could define a subset of drug pairs with
      strong interaction in both standard cell lines and glioma-initiating cell
      cultures. In particular, a subset of pairs involving the pharmaceutical compounds
      rimcazole, sertraline, pterostilbene, and gefitinib showed a strong interaction
      in a majority of the cell cultures tested. Statistical modeling of microarray and
      interaction data using sparse canonical correlation analysis revealed several
      predictive biomarkers, which we propose could be of importance in regulating drug
      pair responses. CONCLUSION: We identify novel candidate drug pairs for GBM and
      suggest possibilities to prospectively use transcriptional biomarkers to predict
      drug interactions in individual cases.

PMID- 24101738
TI  - Neuropsychological functions and quality of life in survived patients with
      intracranial germ cell tumors after treatment.
AB  - BACKGROUND: The notable survival chances of intracranial germ cell tumors
      (icGCTs) lead to a rising concern over long-term neurocognitive outcome. Yet,
      prior evidence related to this issue fails to provide a comprehensive examination
      of the effects of tumor location and radiotherapy. We attempt to explore their
      impacts on the neuropsychological functions and life quality in children with
      icGCT after multimodality treatments. METHODS: A retrospective review of 56
      patients diagnosed with icGCTs at age <20 and treated at the Taipei Veterans
      General Hospital was provided. Intelligence, memory, visual organization,
      attention, and executive function were assessed by neurocognitive tests;
      adaptation to life, emotional and behavioral changes, interpersonal
      relationships, and impact on the family were evaluated by parent-report
      instruments. Effects of tumor locations (germinomas and nongerminomatous
      malignant germ cell tumors in the pineal, suprasellar, and basal ganglia) and
      irradiation on these measurements were examined. RESULTS: Patients with tumors in
      the basal ganglia region had lower full-scale IQs than those with tumors in the
      pineal or suprasellar regions. Subscores of intelligence scale and short-term
      retention of verbal and visual stimuli showed evident group differences, as did
      the quality of life and adaptive skills, particularly in psychosocial domains.
      Patients treated with whole-ventricular irradiation had better outcomes.
      Extensive irradiation field and high irradiation dosage influenced intellectual
      functions, concept crystallization, executive function, and memory. CONCLUSIONS:
      Tumor location and irradiation field/dosage appear to be the crucial factors
      related to certain neuropsychological, emotional, and behavioral dysfunctions
      that in turn alter the quality of life in children with icGCTs who survive after
      treatment.

PMID- 24101739
TI  - Proton radiotherapy for pediatric central nervous system ependymoma: clinical
      outcomes for 70 patients.
AB  - BACKGROUND: Ependymoma is treated with maximal surgical resection and localized
      radiotherapy. Minimizing unnecessary exposure to radiation is of paramount
      importance for young children. Proton radiotherapy (PRT) spares healthy tissues
      outside the target region, but reports of clinical outcomes are scarce. We report
      outcomes for 70 patients treated with PRT for intracranial ependymoma. METHODS:
      Seventy patients with localized ependymoma treated with involved-field PRT at the
      Massachusetts General Hospital between October 2000 and February 2011 were
      included. RESULTS: Median age at diagnosis was 38 months (range, 3 mo-20 y).
      Nineteen (27%) patients had supratentorial ependymoma and 51(73%) had
      infratentorial ependymoma. Forty-six (66%) had gross total resection (GTR), and
      24 (34%) had subtotal resection (STR). At a median follow-up of 46 months, 3-year
      local control, progression-free survival, and overall survival were 83%, 76%, and
      95%, respectively. STR was significantly associated with worse progression-free
      survival (54% vs 88%, P = .001) and overall survival (90% vs 97% for GTR, P =
      .001). In a subset of patients (n = 14), mean intelligence was 108.5 at baseline
      and 111.3 after mean 2.05 years of follow-up. In a larger group of patients (n =
      28), overall adaptive skills were 100.1 at baseline and 100.8 after 2.21 years of
      follow-up. Few patients developed evidence of growth hormone deficiency,
      hypothyroidism, or hearing loss. CONCLUSION: Outcomes for children treated with
      PRT compare favorably with the literature. STR correlated with inferior outcome.
      The young age at diagnosis and the proximity of critical structures in patients
      with ependymoma make PRT an ideal radiation modality.

PMID- 24101740
TI  - CLAHRCs in practice: combined knowledge transfer and exchange strategies,
      cultural change, and experimentation.
AB  - OBJECTIVES: The nine NIHR CLAHRCs are collaborations between universities and
      local NHS organizations that seek to improve patient outcomes through the conduct
      and application of applied health research. The theoretical and practical context
      within which the CLAHRCs were set up was characterized by a considerable degree
      of uncertainty, and the CLAHRCs were established as a natural experiment.
      METHODS: We adopted a formative and emergent evaluation approach. Drawing on in
      depth, multi-method case studies of two CLAHRCs we explored how they pursued
      their remit by supporting efforts to increase the relevance and use of health
      research, and building relationships. RESULTS: Both CLAHRCs: strengthened local
      networks and relationships; built capacity in their local academic and NHS
      communities to undertake and use research that meets the needs of the service;
      developed research and implementation methodologies; and added to understanding
      of the complex relation between research and implementation. There was evidence
      of impact of CLAHRC projects on health and social care services. Informed by the
      literature on implementing collaborative research initiatives, knowledge transfer
      and exchange and cultural change, some key lessons can be drawn. CONCLUSION: The
      CLAHRCs pursued a strategy that can be categorized as one of flexible
      comprehensiveness; i.e. their programmes have been flexible and responsive and
      they have used a range of approaches that seek to match the diverse aspects of
      the complex issues they face. Key features include their work on combining a
      range of knowledge transfer and exchange strategies, their efforts to promote
      cultural change, and the freedom to experiment, learn and adapt. Although the
      CLAHRCs do not, by themselves, have the remit or resources to bring about
      wholesale service improvement in health care, they do have features that would
      allow them to play a key role in some of the wider initiatives that encourage
      innovation.

PMID- 24101741
TI  - Tribulations of stroke trials.

PMID- 24101742
TI  - Prolonged social withdrawal disorder: a hikikomori case in Spain.
AB  - BACKGROUND: The Japanese term hikikomori means literally 'to be confined'. Social
      withdrawal can be present in severe psychiatric disorders; however, in Japan,
      hikikomori is a defined nosologic entity. There have been only a few reported
      cases in occidental culture. MATERIAL: We present a case report of a Spanish man
      with prolonged social withdrawal lasting for 4 years. DISCUSSION: This is a case
      of prolonged social withdrawal not bound to culture, as well as the second case
      of hikikomori reported in Spain. We propose prolonged social withdrawal disorder
      as a disorder not linked to culture, in contrast to hikikomori. CONCLUSION:
      Further documentation of this disorder is still needed to encompass all cases
      reported in Japan and around the world.

PMID- 24101743
TI  - Microbial basis of oral malodor development in humans.
AB  - To better understand the microbial basis of oral malodor development in humans,
      we used a cross-sectional and longitudinal study design and the pyrosequencing
      approach to track and compare the tongue microbiota associated with oral malodor
      in 29 Chinese adults who underwent a consecutive three-day evaluation for the
      amount of H2S excreted orally. Three levels of the oral malodor state (healthy,
      oral malodor, and severe oral malodor) were defined based on the H2S level.
      Community structure of the tongue plaques was more sensitive to changes of
      malodor state than to interpersonal variations or differences in sampling times.
      Within each individual, the structure of microbiota was relatively stable, while
      their variations were correlated with the change in the H2S level. Severe oral
      malodor microbiota were the most conserved in community structure, whereas the
      healthy ones were relatively varied. Oral-malodor-associated bacteria were
      identified. The relative abundance of Leptotrichia and Prevotella was positively
      correlated with oral malodor severity, whereas Hemophilus and Gemella exhibited a
      negative relationship with oral malodor severity. Our study provides one of the
      first landscapes of oral microbiota changes associated with oral malodor
      development and reveals microbes potentially useful to the evaluation and control
      of oral malodor. 

PMID- 24101744
TI  - Twice-daily dosing of RDZ no longer recommended for treatment of intestinal
      Tritrichomonas foetus infection.

PMID- 24101745
TI  - Ventral occipito-atlanto-axial fluid-filled lesion causing dynamic spinal cord
      compression in a cat.
AB  - Cystic lesions affecting the vertebral canal or spinal cord have rarely been
      reported in cats. A 3-year-old female neutered domestic longhair cat presented
      for evaluation of a 2-year-history of episodes of ataxia and paresis affecting
      all limbs. Neurological examination was consistent with a lesion in the C1-C5
      spinal cord segments. Magnetic resonance imaging (MRI) showed a fluid-filled
      lesion at the occipito-atlanto-axial region causing dynamic spinal cord
      compression on flexion of the neck. The imaging characteristics were compatible
      with a juxta-articular cyst. To our knowledge, this is the first report of a
      fluid-filled lesion causing dynamic cervical spinal cord compression in a cat and
      highlights the importance of performing flexion-extension MRI views in diagnosing
      cases with dynamic spinal cord compression. 

PMID- 24101746
TI  - Pyogranulomatous mural folliculitis in a cat treated with methimazole.
AB  - An 11-year-old spayed female domestic shorthair cat was presented for polydipsia,
      hyperactivity and bilateral thyroid gland enlargement. Total T4 (TT4) was in the
      upper interval range; therefore, an early hyperthyroidism was suspected. A
      treatment trial with methimazole was started, as the owner refused further tests.
      Six months later the owner stopped the treatment. One year later, clinical signs
      persisted and TT4 was still in the upper interval range. Methimazole was re
      introduced but 48 h later the cat presented non-pruritic alopecia with erythema,
      scales and perilesional yellowish crusts. Pyogranulomatous mural folliculitis was
      diagnosed by histopatological examination of the skin biopsies. Methimazole was
      withdrawn and macroscopic lesions healed and disappeared histologically in 15
      days. An idiosyncratic drug reaction to methimazole was suspected. To the best of
      our knowledge, this is the first report of feline pyogranulomatous mural
      folliculitis likely secondary to an adverse drug reaction to methimazole
      administration. 

PMID- 24101747
TI  - Helping the helpers: mindfulness training for burnout in pediatric oncology--a
      pilot program.
AB  - BACKGROUND: Burnout, a syndrome of emotional exhaustion, depersonalization, and
      diminished feelings of accomplishment, is common among pediatric oncology staff.
      This study explores a mindfulness-based course (MBC) to decrease burnout in a
      multidisciplinary group of pediatric oncology staff members in the United States
      and Israel. MATERIALS AND METHODS: Forty-eight participants, mostly nurses, were
      randomized to either the MBC intervention or a control group. MBC participants
      received eight weekly sessions of mindfulness education. The primary outcome
      studied was burnout. Secondary outcomes studied included depression and perceived
      stress. RESULTS: Nearly 100% of the subjects exhibited signs of burnout at
      baseline and MBC did not result in any significant improvement in scores on
      burnout, perceived stress or depression scales. Qualitative analysis of diaries
      kept by subjects revealed reduced stress, improved inner peace, compassion and
      joy, better focus and self-awareness and less somatic symptoms in the
      intervention arm. CONCLUSIONS: Burnout is a major problem in pediatric oncology
      staff. Mindfulness practices can be taught in the workplace and may be a useful
      component of a multidimensional strategy to reduce burnout in this population.

PMID- 24101748
TI  - Bilateral cerebellar hemorrhage in vermian vein thrombosis.

PMID- 24101749
TI  - Childhood obesity and risk of pediatric multiple sclerosis and clinically
      isolated syndrome.

PMID- 24101750
TI  - Nonmydriatic ocular fundus photography among headache patients in an emergency
      department.

PMID- 24101752
TI  - Clinical reasoning: a case of abnormal eye movements in an infant: more than
      meets the eye.

PMID- 24101753
TI  - Teaching video neuroimages: perioral myoclonia with absences in a 12-year-old
      boy.

PMID- 24101754
TI  - Teaching neuroimages: IgG4-related orbital disease and enlargement of the
      trigeminal nerve branches.

PMID- 24101755
TI  - Clinical utility of the Colorado Learning Difficulties Questionnaire.
AB  - BACKGROUND AND OBJECTIVE: Behavioral disorders are highly comorbid with childhood
      learning disabilities (LDs), and accurate identification of LDs is vital for
      guiding appropriate interventions. However, it is difficult to conduct
      comprehensive assessment of academic skills within the context of primary care
      visits, lending utility to screening of academic skills via informant reports.
      The current study evaluated the clinical utility of a parent-reported screening
      measure in identifying children with learning difficulties. METHODS: Participants
      included 440 children (66.7% male), ages 5.25 to 17.83 years (mean = 10.32 years,
      SD = 3.06 years), referred for neuropsychological assessment. Academic
      difficulties were screened by parent report using the Colorado Learning
      Difficulties Questionnaire (CLDQ). Reading and math skills were assessed via
      individually administered academic achievement measures. Sensitivity,
      specificity, classification accuracy, and conditional probabilities were
      calculated to evaluate the efficacy of the CLDQ in predicting academic
      impairment. RESULTS: Correlations between the CLDQ reading scale and reading
      achievement measures ranged from -0.35 to -0.65 and from -0.24 to -0.46 between
      the CLDQ math scale and math achievement measures (all P < .01). Sensitivity was
      good for both reading and math scales, whereas specificity was low. Taking into
      account the high base rate of reading and math LDs within our sample, the
      conditional probability of true negatives (96.2% reading, 85.1% math) was higher
      than for true positives (40.5% reading, 37.9% math). CONCLUSIONS: Overall, the
      CLDQ may more accurately predict children without LDs than children with LDs. As
      such, the absence of parent-reported difficulties may be adequate to rule out an
      overt LD, whereas elevated scores likely indicate the need for more comprehensive
      assessment.

PMID- 24101756
TI  - Approval and perceived impact of duty hour regulations: survey of pediatric
      program directors.
AB  - OBJECTIVES: To determine pediatric program director (PD) approval and perception
      of changes to resident training and patient care resulting from 2011
      Accreditation Council for Graduate Medical Education (ACGME) Common Program
      Requirements. METHODS: All US pediatric PDs (n = 181) were identified from the
      ACGME. Functional e-mail addresses were identified for 164 (90.6%). Three
      individualized e-mail requests were sent to each PD to complete an anonymous 32
      question Web-based survey. RESULTS: A total of 151 responses were obtained
      (83.4%). Pediatrics PDs reported approval for nearly all of the 2011 ACGME duty
      hour regulations except for 16-hour intern shift limits (72.2% disapprove).
      Regarding the perceived impact of the new standards, many areas were reportedly
      unchanged, but most PDs reported negative effects on resident education (74.7%),
      preparation for senior roles (79.9%), resident ownership of patients (76.8%), and
      continuity of care (78.8%). There was a reported increase in PD workload (67.6%)
      and use of physician extenders (62.7%). Finally, only 48.3% of PDs reported that
      their residents are "always" compliant with 2011 requirements. CONCLUSIONS:
      Pediatric PDs think there have been numerous negative consequences of the 2011
      Common Program Requirements. These include declines in resident education and
      preparation to take on more senior roles, as well as diminished resident
      accountability and continuity of care. Although they support individual aspects
      of duty hour regulation, almost three-quarters of pediatric PDs say there should
      be fewer regulations. The opinions expressed by PDs in this study should prompt
      research using quantitative metrics to assess the true impact of duty hour
      regulations.

PMID- 24101757
TI  - Autoimmune lymphoproliferative syndrome misdiagnosed as hemophagocytic
      lymphohistiocytosis.
AB  - Autoimmune lymphoproliferative syndrome (ALPS) is a rare inherited disorder of
      apoptosis, most commonly due to mutations in the FAS (TNFRSF6) gene. It presents
      with chronic lymphadenopathy, splenomegaly, and symptomatic multilineage
      cytopenias in an otherwise healthy child. Unfortunately, these clinical findings
      are also noted in other childhood lymphoproliferative conditions, such as
      leukemia, lymphoma, and hemophagocytic lymphohistiocytosis, which can confound
      the diagnosis. This report describes a 6-year-old girl with symptoms misdiagnosed
      as hemophagocytic lymphohistiocytosis and treated with chemotherapy before the
      recognition that her symptoms and laboratory values were consistent with a
      somatic FAS mutation leading to ALPS. This case should alert pediatricians to
      include ALPS in the differential diagnosis of a child with lymphadenopathy,
      splenomegaly, and cytopenias; obtain discriminating screening laboratory
      biomarkers, such as serum vitamin B-12 and ferritin levels; and, in the setting
      of a highly suspicious clinical scenario for ALPS, pursue testing for somatic FAS
      mutations when germ-line mutation testing is negative. 

PMID- 24101758
TI  - Screening for primary hypertension in children and adolescents: U.S. Preventive
      Services Task Force recommendation statement.
AB  - DESCRIPTION: Update of the 2003 U.S. Preventive Services Task Force (USPSTF)
      recommendation on screening for high blood pressure in children and adolescents.
      METHODS: The USPSTF reviewed the evidence on screening and diagnostic accuracy of
      screening tests for blood pressure in children and adolescents, the effectiveness
      and harms of treatment of screen-detected primary childhood hypertension, and the
      association of hypertension with markers of cardiovascular disease in childhood
      and adulthood. POPULATION: This recommendation applies to children and
      adolescents who do not have symptoms of hypertension. RECOMMENDATION: The USPSTF
      concludes that the current evidence is insufficient to assess the balance of
      benefits and harms of screening for primary hypertension in asymptomatic children
      and adolescents to prevent subsequent cardiovascular disease in childhood or
      adulthood.

PMID- 24101759
TI  - Apnea in children hospitalized with bronchiolitis.
AB  - OBJECTIVE: To identify risk factors for inpatient apnea among children
      hospitalized with bronchiolitis. METHODS: We enrolled 2207 children, aged <2
      years, hospitalized with bronchiolitis at 16 sites during the winters of 2007 to
      2010. Nasopharyngeal aspirates (NPAs) were obtained on all subjects, and real
      time polymerase chain reaction was used to test NPA samples for 16 viruses.
      Inpatient apnea was ascertained by daily chart review, with outcome data in 2156
      children (98%). Age was corrected for birth <37 weeks. Multivariable logistic
      regression was performed to identify independent risk factors for inpatient
      apnea. RESULTS: Inpatient apnea was identified in 108 children (5%, 95%
      confidence interval [CI] 4%-6%). Statistically significant, independent
      predictors of inpatient apnea included: corrected ages of <2 weeks (odds ratio
      [OR] 9.67) and 2 to 8 weeks (OR 4.72), compared with age >= 6 months; birth
      weight <2.3 kg (5 pounds; OR 2.15), compared with >= 3.2 kg (7 pounds); caretaker
      report of previous apnea during this bronchiolitis episode (OR 3.63);
      preadmission respiratory rates of <30 (OR 4.05), 30 to 39 (OR 2.35) and >70 (OR
      2.26), compared with 40 to 49; and having a preadmission room air oxygen
      saturation <90% (OR 1.60). Apnea risk was similar across the major viral
      pathogens. CONCLUSIONS: In this prospective, multicenter study of children
      hospitalized with bronchiolitis, inpatient apnea was associated with younger
      corrected age, lower birth weight, history of apnea, and preadmission clinical
      factors including low or high respiratory rates and low room air oxygen
      saturation. Several bronchiolitis pathogens were associated with apnea, with
      similar apnea risk across the major viral pathogens.

PMID- 24101761
TI  - Early feeding and risk of celiac disease in a prospective birth cohort.
AB  - OBJECTIVES: Timing of gluten introduction has been associated with the risk of
      celiac disease (CD) in children, but the optimal time window is unknown. We aimed
      to study the effect of age of gluten introduction on the risk of CD, adjusting
      for continued breastfeeding. METHODS: In The Norwegian Mother and Child Cohort
      Study, a prospective birth cohort including 107,000 children, CD was identified
      by questionnaires and by linkage to the Norwegian Patient Register. Gluten
      introduction was reported monthly from 0 to 6 months of age, and breastfeeding
      from 0 to 18 months. RESULTS: After exclusion of cases with insufficient
      information, 324 children with CD in a cohort of 82,167 were used in the
      analyses. Gluten was introduced before or at 4 months in 8.0%, 5 to 6 months in
      45.3%, and after 6 months in 46.6%, whereas continued breastfeeding was stable at
      ~ 78% at 6 months age. CD was diagnosed in 3.68/1000 of the infants with gluten
      introduction at 5 to 6 months compared with 4.15/1000 with late and 4.24/1000
      with early gluten introduction. After adjustment for the child's age and gender,
      breastfeeding, and maternal CD, delayed gluten introduction was associated with
      an increased risk of CD (adjusted odds ratio, 1.27 [95% confidence interval, 1.01
      1.65], P = .045). Breastfeeding >12 months was also associated with increased
      risk (adjusted odds ratio, 1.49 [95% confidence interval, 1.01-2.21], P = .046).
      CONCLUSIONS: We found an increased risk of CD in children introduced to gluten
      after 6 months and a higher risk in children breastfed after 12 months age.

PMID- 24101760
TI  - Parent health and functioning 13 months after infant or child NICU/PICU death.
AB  - BACKGROUND: After a child's death, parents may experience depression,
      posttraumatic stress disorder (PTSD), and increased risk for cancers, diabetes,
      psychiatric hospitalization, and suicide. Racial/ethnic differences are unknown.
      This longitudinal study investigated health and functioning of Hispanic, black,
      and white parents through 13 months after NICU/PICU death. METHODS: Parents (176
      mothers, 73 fathers) of 188 deceased infants/children were recruited from 4
      NICUs, 4 PICUs, and state death certificates 2 to 3 weeks after death. Deaths
      occurred after limiting treatment/withdrawing life support (57%), unsuccessful
      resuscitation (32%), or brain death (11%). Data on parent physical health
      (hospitalizations, chronic illness), mental health (depression, PTSD, alcohol
      use), and functioning (partner status, employment) were collected in the home at
      1, 3, 6, and 13 months after death. RESULTS: Mean age for mothers was 32 +/- 8,
      fathers 37 +/- 9; 79% were Hispanic or black. Thirteen months after infant/child
      death, 72% of parents remained partnered, 2 mothers had newly diagnosed cancer,
      alcohol consumption was below problem drinking levels, parents had 98
      hospitalizations (29% stress related) and 132 newly diagnosed chronic health
      conditions, 35% of mothers and 24% of fathers had clinical depression, and 35% of
      mothers and 30% of fathers had clinical PTSD. At 6 months after infant/child
      death, 1 mother attempted suicide. Week 1 after infant/child death, 9% of mothers
      and 32% of fathers returned to employment; 7 parents took no time off. More
      Hispanic and black mothers than white mothers had moderate/severe depression at 6
      months after infant/child death and PTSD at every time point. CONCLUSIONS:
      Parents, especially minority mothers, have negative physical and mental health
      outcomes during the first year after NICU/PICU death.

PMID- 24101762
TI  - Athlete endorsements in food marketing.
AB  - OBJECTIVE: This study quantified professional athletes' endorsement of food and
      beverages, evaluated the nutritional quality of endorsed products, and determined
      the number of television commercial exposures of athlete-endorsement commercials
      for children, adolescents, and adults. METHODS: One hundred professional athletes
      were selected on the basis of Bloomberg Businessweek's 2010 Power 100 rankings,
      which ranks athletes according to their endorsement value and prominence in their
      sport. Endorsement information was gathered from the Power 100 list and the
      advertisement database AdScope. Endorsements were sorted into 11 endorsement
      categories (eg, food/beverages, sports apparel). The nutritional quality of the
      foods featured in athlete-endorsement advertisements was assessed by using a
      Nutrient Profiling Index, whereas beverages were evaluated on the basis of the
      percentage of calories from added sugar. Marketing data were collected from
      AdScope and Nielsen. RESULTS: Of 512 brands endorsed by 100 different athletes,
      sporting goods/apparel represented the largest category (28.3%), followed by
      food/beverages (23.8%) and consumer goods (10.9%). Professional athletes in this
      sample were associated with 44 different food or beverage brands during 2010.
      Seventy-nine percent of the 62 food products in athlete-endorsed advertisements
      were energy-dense and nutrient-poor, and 93.4% of the 46 advertised beverages had
      100% of calories from added sugar. Peyton Manning (professional American football
      player) and LeBron James (professional basketball player) had the most
      endorsements for energy-dense, nutrient-poor products. Adolescents saw the most
      television commercials that featured athlete endorsements of food. CONCLUSIONS:
      Youth are exposed to professional athlete endorsements of food products that are
      energy-dense and nutrient-poor.

PMID- 24101763
TI  - Impact of a routine two-dose varicella vaccination program on varicella
      epidemiology.
AB  - OBJECTIVE: One-dose varicella vaccination for children was introduced in the
      United States in 1995. In 2006, a second dose was recommended to further decrease
      varicella disease and outbreaks. We describe the impact of the 2-dose vaccination
      program on varicella incidence, severity, and outbreaks in 2 varicella active
      surveillance areas. METHODS: We examined varicella incidence rates and disease
      characteristics in Antelope Valley (AV), CA, and West Philadelphia, PA, and
      varicella outbreak characteristics in AV during 1995-2010. RESULTS: In 2010,
      varicella incidence was 0.3 cases per 1000 population in AV and 0.1 cases per
      1000 population in West Philadelphia: 76% and 67% declines, respectively, since
      2006 and 98% declines in both sites since 1995; incidence declined in all age
      groups during 2006-2010. From 2006-2010, 61.7% of case patients in both
      surveillance areas had been vaccinated with 1 dose of varicella vaccine and 7.5%
      with 2 doses. Most vaccinated case patients had <50 lesions with no statistically
      significant differences among 1- and 2-dose cases (62.8% and 70.3%,
      respectively). Varicella-related hospitalizations during 2006-2010 declined >40%
      compared with 2002-2005 and >85% compared with 1995-1998. Twelve varicella
      outbreaks occurred in AV during 2007-2010, compared with 47 during 2003-2006 and
      236 during 1995-1998 (P < .01). CONCLUSIONS: Varicella incidence,
      hospitalizations, and outbreaks in 2 active surveillance areas declined
      substantially during the first 5 years of the 2-dose varicella vaccination
      program. Declines in incidence across all ages, including infants who are not
      eligible for varicella vaccination, and adults, in whom vaccination levels are
      low, provide evidence of the benefit of high levels of immunity in the
      population.

PMID- 24101765
TI  - Patient safety, work hour regulations, and resident education.

PMID- 24101764
TI  - Central line maintenance bundles and CLABSIs in ambulatory oncology patients.
AB  - OBJECTIVE: Pediatric oncology patients are frequently managed with central lines
      as outpatients, and these lines confer significant morbidity in this immune
      compromised population. We aimed to investigate whether a multidisciplinary,
      central line maintenance care bundle reduces central line-associated bloodstream
      infections (CLABSIs) and bacteremias in ambulatory pediatric oncology patients.
      METHODS: We conducted an interrupted time-series study of a maintenance bundle
      concerning all areas of central line care. Each of 3 target groups (clinic staff,
      homecare agency nurses, and patient families) (1) received training on the bundle
      and its importance, (2) had their practice audited, and (3) were shown CLABSI
      rates through graphs, in-service training, and bulletin boards. CLABSI and
      bacteremia person-time incidence rates were collected for 23 months before and 24
      months after beginning the intervention and were compared by using a Poisson
      regression model. RESULTS: The mean CLABSI rate decreased by 48% from 0.63
      CLABSIs per 1000 central line days at baseline to 0.32 CLABSIs per 1000 central
      line days during the intervention period (P = .005). The mean bacteremia rate
      decreased by 54% from 1.27 bacteremias per 1000 central line days at baseline to
      0.59 bacteremias per 1000 central line days during the intervention period (P <
      .001). CONCLUSIONS: Implementation of a multidisciplinary, central line
      maintenance care bundle significantly reduced CLABSI and bacteremia person-time
      incidence rates in ambulatory pediatric oncology patients with central lines.
      Further research is needed to determine if maintenance care bundles reduce
      ambulatory CLABSIs and bacteremia in other adult and pediatric populations.

PMID- 24101767
TI  - When life-sustaining treatment is withdrawn and the patient doesn't die.
AB  - One of the most difficult decisions that doctors and parents must make is the
      decision to withdraw life-sustaining treatment. Doctors find it easier to
      withdraw treatments in situations where withdrawal will be rapidly fatal rather
      than in situations in which treatment withdrawal will lead to a prolonged dying
      process. Mechanical ventilation is usually such a treatment. Withdrawal of
      ventilation generally leads to the patient's rapid demise. Doctors may tell
      parents that death will occur quickly after a ventilator is withdrawn. But what
      happens when the doctors are wrong and a patient survives without life support?
      What should doctors do next? We present a case in which that happened and asked 3
      experts to comment on the case. Stefan Kutzsche is a senior consultant in
      neonatology at Oslo University Hospital Ulleval in Norway. John Colin Partridge
      is a neonatologist and professor of pediatrics at University of California, San
      Francisco. Steven R. Leuthner is a neonatologist and professor of pediatrics and
      bioethics at the Medical College of Wisconsin. They each recommend slightly
      different approaches to this dilemma. 

PMID- 24101766
TI  - Prenatal exposure to air pollution, maternal psychological distress, and child
      behavior.
AB  - BACKGROUND: Airborne polycyclic aromatic hydrocarbons (PAHs) are pollutants
      generated by combustion of fossil fuel and other organic material. Both prenatal
      PAH exposure and maternal psychological distress during pregnancy have each been
      associated with neurodevelopmental problems in children. The goal was to evaluate
      potential interactions between prenatal exposure to airborne PAHs and maternal
      psychological distress during pregnancy on subsequent behavioral problems in
      children. METHODS: In a longitudinal birth cohort study, 248 children of
      nonsmoking white women in the coal-burning region of Krakow, Poland, were
      followed from in utero until age 9. Prenatal PAH exposure was measured by
      personal air monitoring during pregnancy, maternal demoralization during
      pregnancy by the Psychiatric Epidemiology Research Instrument-Demoralization, and
      child behavior by the Child Behavior Checklist. RESULTS: Significant interactions
      between maternal demoralization and PAH exposure (high versus low) were
      identified for symptoms of anxious/depressed, withdrawn/depressed, social
      problems, aggressive behavior, internalizing problems, and externalizing
      problems. The effects of demoralization on syndromes of anxious/depressed,
      withdrawn/depressed, rule-breaking, aggressive behavior, and the composite
      internalizing and externalizing scores were seen only in conjunction with high
      PAH exposure. Fewer significant effects with weaker effect sizes were observed in
      the low-PAH-exposure group. CONCLUSIONS: Maternal demoralization during pregnancy
      appears to have a greater effect on child neurobehavioral development among
      children who experienced high prenatal PAH exposure. The results provide the
      first evidence of an interaction between prenatal exposure to maternal
      demoralization and air pollution on child neurobehavioral development, indicating
      the need for a multifaceted approach to the prevention of developmental problems
      in children.

PMID- 24101768
TI  - Childhood anemia at high altitude: risk factors for poor outcomes in severe
      pneumonia.
AB  - BACKGROUND: Pneumonia is the leading cause of mortality in young children
      globally, and factors that affect tissue delivery of oxygen may affect outcomes
      of pneumonia. We studied whether altitude and anemia influence disease severity
      and outcomes in young children with World Health Organization-defined severe
      pneumonia. METHODS: We analyzed data from the SPEAR (Severe Pneumonia Evaluation
      Antimicrobial Research) study, a World Health Organization- and USAID-sponsored
      multinational randomized controlled trial of antibiotics for severe pneumonia
      among children aged 2 to 59 months in resource-poor settings. The trial enrolled
      958 children in 8 sites at varying elevations, classified as high (>= 2000 m) or
      low (<2000 m) altitude. We compared illness severity and assessed the effect of
      anemia on treatment outcome at high and low altitudes, adjusting for potential
      confounders and study site. RESULTS: Children at high altitudes had significantly
      lower oxygen saturation on presentation, more cyanosis, lower systolic blood
      pressure, and higher hemoglobin. After adjusting for potential confounders,
      anemia predicted treatment failure in children living at high altitude (relative
      risk: 4.07; 95% confidence interval: 2.60-6.38) but not at low altitude (relative
      risk: 1.12; 95% confidence interval: 0.96-1.30). Children at high altitude took
      longer to reach normoxemia than did children at lower altitudes (5.25 vs 0.75
      days; P < .0001). CONCLUSIONS: Children at high altitude present with more severe
      disease, and children with anemia at high altitude are at greater risk of poor
      outcome when being treated for severe pneumonia. Given the high global prevalence
      of anemia among young children, prevention and treatment of anemia should be a
      priority in children living at high altitude and could improve outcomes of
      pneumonia.

PMID- 24101769
TI  - Maternal influence on child HPA axis: a prospective study of cortisol levels in
      hair.
AB  - OBJECTIVE: To investigate cortisol concentrations in hair as biomarker of
      prolonged stress in young children and their mothers and the relation to
      perinatal and sociodemographic factors. METHODS: Prospective cohort study of 100
      All Babies In Southeast Sweden study participants with repeated measures at 1, 3,
      5, and 8 years and their mothers during pregnancy. Prolonged stress levels were
      assessed through cortisol in hair. A questionnaire covered perinatal and
      sociodemographic factors during the child's first year of life. RESULTS: Maternal
      hair cortisol during the second and third trimester and child hair cortisol at
      year 1 and 3 correlated. Child cortisol in hair levels decreased over time and
      correlated to each succeeding age, between years 1 and 3 (r = 0.30, P = .002), 3
      and 5 (r = 0.39, P < .001), and 5 and 8 (r = 0.44, P < .001). Repeated measures
      gave a significant linear association over time (P < .001). There was an
      association between high levels of hair cortisol and birth weight (beta = .224, P
      = .020), nonappropriate size for gestational age (beta = .231, P = .017), and
      living in an apartment compared with a house (beta = .200, P = .049). In
      addition, we found high levels of cortisol in hair related to other factors
      associated with psychosocial stress exposure. CONCLUSIONS: Correlation between
      hair cortisol levels in mothers and their children suggests a heritable trait or
      maternal calibration of the child's hypothalamic-pituitary-adrenocortical axis.
      Cortisol output gradually stabilizes and seems to have a stable trait. Cortisol
      concentration in hair has the potential to become a biomarker of prolonged
      stress, especially applicable as a noninvasive method when studying how stress
      influences children's health.

PMID- 24101770
TI  - Evidence of improved milk intake after frenotomy: a case report.
AB  - Ankyloglossia (tongue tie) is a well-recognized cause of breastfeeding
      difficulties and, if untreated, can cause maternal nipple pain and trauma,
      ineffective feeding, and poor infant weight gain. In some cases, this condition
      will result in a downregulation of the maternal milk supply. Milk-production
      measurements (24-hour) for a breastfeeding infant with ankyloglossia revealed the
      ineffective feeding of the infant (78 mL/24 hours), and a low milk supply (350
      mL/24 hours) was diagnosed. Appropriate management increased milk supply (1254
      mL/24 hours) but not infant milk intake (190 mL/24 hours). Test weighing
      convincingly revealed the efficacy of frenotomy, increasing breastfeeding milk
      transfer from 190 to 810 mL/24 hours. Postfrenotomy, breastfeeding almost
      completely replaced bottle-feeding of expressed breast milk. This case study
      confirms that ankyloglossia may reduce maternal milk supply and that frenotomy
      can improve milk removal by the infant. Milk-production measurements (24-hour)
      provided the evidence to confirm these findings. 

PMID- 24101771
TI  - Facing persistent challenges in pediatric decision-making: new Hastings Center
      guidelines.

PMID- 24101774
TI  - At the crossroads: transforming health systems to address women's health across
      the life course.

PMID- 24101775
TI  - Rallying United Nations organizations in the fight against noncommunicable
      diseases.

PMID- 24101772
TI  - Stress-induced cytokinin synthesis increases drought tolerance through the
      coordinated regulation of carbon and nitrogen assimilation in rice.
AB  - The effects of water deficit on carbon and nitrogen metabolism were investigated
      in flag leaves of wild-type and transgenic rice (Oryza sativa japonica 'Kitaake')
      plants expressing ISOPENTENYLTRANSFERASE (IPT; encoding the enzyme that mediates
      the rate-limiting step in cytokinin synthesis) under the control of P(SARK), a
      maturation- and stress-induced promoter. While the wild-type plants displayed
      inhibition of photosynthesis and nitrogen assimilation during water stress,
      neither carbon nor nitrogen assimilation was affected by stress in the transgenic
      P(SARK)::IPT plants. In the transgenic plants, photosynthesis was maintained at
      control levels during stress and the flag leaf showed increased sucrose (Suc)
      phosphate synthase activity and reduced Suc synthase and invertase activities,
      leading to increased Suc contents. The sustained carbon assimilation in the
      transgenic P(SARK)::IPT plants was well correlated with enhanced nitrate content,
      higher nitrate reductase activity, and sustained ammonium contents, indicating
      that the stress-induced cytokinin synthesis in the transgenic plants played a
      role in maintaining nitrate acquisition. Protein contents decreased and free
      amino acids increased in wild-type plants during stress, while protein content
      was preserved in the transgenic plants. Our results indicate that the stress
      induced cytokinin synthesis in the transgenic plants promoted sink strengthening
      through a cytokinin-dependent coordinated regulation of carbon and nitrogen
      metabolism that facilitates an enhanced tolerance of the transgenic plants to
      water deficit.

PMID- 24101777
TI  - The breast cancer conundrum.
AB  - For decades, rates of breast cancer have been going up faster in rich countries
      than in poor ones. Scientists are beginning to understand more about its causes
      but unanswered questions remain. Patrick Adams reports. 

PMID- 24101778
TI  - The new women's health agenda.

PMID- 24101779
TI  - Global mortality trends and patterns in older women.
AB  - OBJECTIVE: To describe mortality patterns in women older than 50 years in light
      of the growth, seen in almost all countries, in the absolute number of females in
      this age group and in the proportion of the female population comprising older
      women. METHODS: National death record data and World Health Organization
      estimates of life expectancy and causes of death in women older than 50 years
      were analysed. Projections of trends in mortality, by cause, at older ages were
      also made. FINDINGS: In both developed and developing countries, the leading
      causes of death among older women were cardiovascular diseases and cancers. In
      countries with death registration data, cardiovascular and (to a lesser extent)
      cancer mortality appears to have declined in older women in recent decades and
      this decline has resulted in improved life expectancy at age 50. If these trends
      continue, deaths in older women are still expected to increase in number because
      of population growth and ageing. CONCLUSION: Noncommunicable diseases, especially
      cardiovascular diseases and cancers, are expected to cause an increasing share of
      women's deaths in low- and middle-income countries owing to the ageing of the
      population and to reductions in child and maternal deaths. Health systems must
      adjust accordingly, perhaps by drawing on lessons from high-income countries that
      have succeeded in reducing mortality from noncommunicable diseases.

PMID- 24101780
TI  - Cervical and female breast cancers in the Americas: current situation and
      opportunities for action.
AB  - OBJECTIVE: To understand better the current regional situation and public health
      response to cervical cancer and female breast cancer in the Americas. METHODS:
      Data on cervical cancer and female breast cancers in 33 countries, for the period
      from 2000 to the last year with available data, were extracted from the Pan
      American Health Organization (PAHO) Regional Mortality Database and analysed.
      Changes in mortality rates over the study period - in all countries except those
      with small populations and large fluctuations in time-series mortality data -
      were calculated using Poisson regression models. Information from the PAHO
      Country Capacity Survey on noncommunicable diseases was also analysed. FINDINGS:
      The Bahamas, Trinidad and Tobago and Uruguay showed relatively high rates of
      death from breast cancer, whereas the three highest rates of death from cervical
      cancer were observed in El Salvador, Nicaragua and Paraguay. Several countries -
      particularly Paraguay and Venezuela - have high rates of death from both types of
      cancer. Although mortality from cervical cancer has generally been decreasing in
      the Americas, decreases in mortality from breast cancer have only been observed
      in a few countries in the Region of the Americas. All but one of the 25 countries
      in the Americas included in the PAHO Country Capacity Survey reported having
      public health services for the screening and treatment of breast and cervical
      cancers. CONCLUSION: Most countries in the Americas have the public health
      capacity needed to screen for - and treat - breast and cervical cancers and,
      therefore, the potential to reduce the burden posed by these cancers.

PMID- 24101781
TI  - Risk factors for noncommunicable chronic diseases in women in China: surveillance
      efforts.
AB  - OBJECTIVE: To investigate risk factors for chronic noncommunicable diseases
      (NCDs) and their determinants in Chinese women. METHODS: Data from the 2010 China
      Chronic Disease and Risk Factor Surveillance survey, comprising a nationally
      representative sample of women, were obtained to determine the prevalence of
      eight risk factors for chronic NCDs: current smoking, harmful use of alcohol,
      insufficient intake of fruit and vegetables, physical inactivity, overweight and
      obesity, raised blood pressure, raised fasting blood glucose and raised total
      serum cholesterol. The mean number of risk factors per woman was estimated. Their
      independent demographic and socioeconomic covariates were also examined with
      ordinal logistic regression. FINDINGS: THE FOLLOWING PREVALENCES WERE FOUND:
      insufficient intake of fruit and vegetables, 51.7%; overweight and obesity,
      32.3%; raised blood pressure, 29.7%; physical inactivity, 18.3%; raised total
      serum cholesterol, 18.1%; raised blood glucose, 7.0%; current smoking, 2.4%; and
      harmful use of alcohol, 1.3%. The mean number of risk factors per woman was 1.61;
      48.0% of the women had at least two risk factors. Women who were older, poorer,
      from rural areas or from eastern or central China had more risk factors, but only
      being more than 35 years old, poorly educated and a resident of eastern or
      central China independently increased the likelihood of having multiple risk
      factors. CONCLUSION: Risk factors for chronic NCDs are common among Chinese women
      aged 18 or older. Interventions to reduce these factors are needed and should
      target women who are older, who live in eastern or central China or who are
      poorly educated.

PMID- 24101782
TI  - A life-course perspective on physical functioning in women.
AB  - OBJECTIVE: To validate Kalache & Kickbusch's model: namely, that functional
      capacity peaks in early adulthood, then declines at a rate dependent on fitness
      level until a "disability threshold" is reached. METHODS: Data came from the
      Australian Longitudinal Study on Women's Health, which followed three cohorts
      from 1996 to 2011: a young, a mid-aged and an older cohort (born in 1973-78, 1946
      51 and 1921-26, respectively). The Short Form (36) Health Survey was used to
      measure physical functioning (score 1-100). The disability threshold was the mean
      physical functioning score in older women requiring assistance with daily
      activities (62.8). The relationship between age and physical functioning was
      modelled using spline regression for the entire sample, and by baseline physical
      functioning quintile and physical activity level. FINDINGS: PHYSICAL DECLINE
      QUICKENED WITH AGE: 0.05 annual units (95% confidence interval, CI: -0.13 to
      0.22) at ages 18-23 years (i.e. no decline); -2.43 (95% CI: -2.64 to -2.23) at
      ages 82-90 years. Decline was faster in quintiles with lower baseline physical
      functioning in the younger and mid-age cohorts and in quintiles with higher
      baseline physical functioning in the older cohort. The disability threshold was
      reached at a mean age of 79 years, but the range was 45-88 years, depending on
      baseline physical functioning and physical activity. CONCLUSION: Age and physical
      decline are not linearly related, as traditionally believed; decline accelerates
      with age. However, baseline physical functioning, but not physical activity,
      influences the rate of decline.

PMID- 24101784
TI  - Why the time is right to tackle breast and cervical cancer in low-resource
      settings.
AB  - The health concerns of women in their mid-adult years - when the prime age of
      reproduction has passed - have been traditionally given little or no attention by
      health systems and donors, despite the heavy burden that diseases such as breast
      and cervical cancer impose on women and their families. The risk of sexually
      transmitted infections that accompanies sexual relations and the risk of death
      and morbidity associated with pregnancy have long been recognized and have
      stimulated major control efforts that are finally yielding positive results. Much
      less attention has been focused, however, on how experiences in early life can
      affect women's health in adulthood. Breast and cervical cancers kill more women
      than any other types of cancer in all parts of the developing world. In most of
      Asia and Latin America and some African countries, deaths from these two forms of
      cancer now outnumber pregnancy-related deaths. There are five compelling reasons
      for focusing on these cancers now to try to reverse these epidemiologic trends:
      (i) the burden of breast and cervical cancer is large and is growing; (ii)
      effective screening and treatment are available; (iii) research is generating new
      knowledge; (iv) there are opportunities for synergy with other health programmes;
      and (v) noncommunicable diseases are the focus of much current interest.

PMID- 24101783
TI  - Differences by sex in the prevalence of diabetes mellitus, impaired fasting
      glycaemia and impaired glucose tolerance in sub-Saharan Africa: a systematic
      review and meta-analysis.
AB  - OBJECTIVE: To assess differences between men and women in the prevalence of
      diabetes mellitus, impaired fasting glycaemia and impaired glucose tolerance in
      sub-Saharan Africa. METHODS: In September 2011, the PubMed and Web of Science
      databases were searched for community-based, cross-sectional studies providing
      sex-specific prevalences of any of the three study conditions among adults living
      in parts of sub-Saharan Africa (i.e. in Eastern, Middle and Southern Africa
      according to the United Nations subregional classification for African
      countries). A random-effects model was then used to calculate and compare the
      odds of men and women having each condition. FINDINGS: In a meta-analysis of the
      36 relevant, cross-sectional data sets that were identified, impaired fasting
      glycaemia was found to be more common in men than in women (OR: 1.56; 95%
      confidence interval, CI: 1.20-2.03), whereas impaired glucose tolerance was found
      to be less common in men than in women (OR: 0.84; 95% CI: 0.72-0.98). The
      prevalence of diabetes mellitus - which was generally similar in both sexes (OR:
      1.01; 95% CI: 0.91-1.11) - was higher among the women in Southern Africa than
      among the men from the same subregion and lower among the women from Eastern and
      Middle Africa and from low-income countries of sub-Saharan Africa than among the
      corresponding men. CONCLUSION: Compared with women in the same subregions, men in
      Eastern, Middle and Southern Africa were found to have a similar overall
      prevalence of diabetes mellitus but were more likely to have impaired fasting
      glycaemia and less likely to have impaired glucose tolerance.

PMID- 24101785
TI  - Innovative public-private partnership: a diagonal approach to combating women's
      cancers in Africa.
AB  - PROBLEM: In low- and middle-income countries, breast and cervical cancer have a
      poor prognosis, partly owing to barriers to treatment. To redress this situation,
      health systems must be strengthened. APPROACH: Pink Ribbon Red Ribbon (PRRR) is
      an innovative partnership designed to leverage public and private investments in
      global health and to build on the successful United States President's Emergency
      Plan for AIDS Relief (PEPFAR) platform to combat cancers of the breast and cervix
      in sub-Saharan Africa and Latin America. By supporting a comprehensive set of
      country-owned and country-driven interventions, PRRR seeks to reduce deaths from
      cervical cancer among women screened and treated through the programme and to
      reduce deaths from breast cancer by promoting early detection. LOCAL SETTING: In
      its initial phase, PRRR is supporting the governments of Botswana, Zambia and
      other countries in expanding cervical cancer prevention, screening and treatment
      coverage - especially to high-risk women with human immunodeficiency virus
      infection - and in strengthening breast cancer education and control services.
      RELEVANT CHANGES: PRRR has introduced a diagonal strategy based on the life
      course and continuum of care approaches to cancer control. Its work has resulted
      in the delivery of the human papillomavirus vaccine to young girls in several
      settings and in the strengthening of prevention, screening and treatment delivery
      systems from the community to the tertiary level. LESSONS LEARNT: This paper
      outlines the approach PRRR has taken as a country-aligned public-private
      partnership and the preliminary lessons learnt, including the need for flexible
      implementation, effective country coordination mechanism and regular
      communication with all stakeholders.

PMID- 24101786
TI  - Integration of comprehensive women's health programmes into health systems:
      cervical cancer prevention, care and control in Rwanda.
AB  - PROBLEM: Although it is highly preventable and treatable, cervical cancer is the
      most common and most deadly cancer among women in Rwanda. APPROACH: By mobilizing
      a diverse coalition of partnerships, Rwanda became the first country in Africa to
      develop and implement a national strategic plan for cervical cancer prevention,
      screening and treatment. LOCAL SETTING: Rwanda - a small, landlocked nation in
      East Africa with a population of 10.4 million - is well positioned to tackle a
      number of "high-burden" noncommunicable diseases. The country's integrated
      response to infectious diseases has resulted in steep declines in premature
      mortality over the past decade. RELEVANT CHANGES: In 2011-2012, Rwanda vaccinated
      227,246 girls with all three doses of the human papillomavirus (HPV) vaccine.
      Among eligible girls, three-dose coverage rates of 93.2% and 96.6% were achieved
      in 2011 and 2012, respectively. The country has also initiated nationwide
      screening and treatment programmes that are based on visual inspection of the
      cervix with acetic acid, testing for HPV DNA, cryotherapy, the loop
      electrosurgical excision procedure and various advanced treatment options.
      LESSONS LEARNT: Low-income countries should begin to address cervical cancer by
      integrating prevention, screening and treatment into routine women's health
      services. This requires political will, cross-sectoral collaboration and
      planning, innovative partnerships and robust monitoring and evaluation. With
      external support and adequate planning, high nationwide coverage rates for HPV
      vaccination and screening for cervical cancer can be achieved within a few years.

PMID- 24101787
TI  - Recommendations towards an integrated, life-course approach to women's health in
      the post-2015 agenda.

PMID- 24101788
TI  - Sexual health in older women.

PMID- 24101789
TI  - Accelerating action towards universal health coverage by applying a gender lens.

PMID- 24101790
TI  - Policy directions to improve women's health beyond reproduction.

PMID- 24101791
TI  - Failure of a VapA/CpG oligodeoxynucleotide vaccine to protect foals against
      experimental Rhocococcus equi pneumonia despite induction of VapA-specific
      antibody and interferon-gamma response.
AB  - We evaluated the immunogenic and protective potential of a recombinant VapA/CpG
      oligodeoxynucleotide (ODN) 2395 vaccine in neonatal foals undergoing experimental
      Rhodococcus equi challenge. Foals (n = 8) were vaccinated by intramuscular
      injection on days 1 and 15 of the study; control foals (n = 7) received a
      phosphate-buffered saline (PBS) solution. All foals were challenged by
      intrabronchial administration of 5 * 106 R. equi 103+ on day 29. Bronchoalveolar
      lavages were done on days 15, 29, and 36 and total cell count, differential cell
      count, rVapA-stimulated cell proliferation and interferon (IFN)-gamma mRNA
      expression determined. Clinical examination, complete blood (cell) counts,
      serology for VapA-specific antibodies, and culture of nasal and fecal swabs were
      done on days 1, 15, 29, 36, 43, and 50. Foals were humanely euthanized on day 50
      and severity of pneumonia scored on a 4-point scale. Vaccination resulted in a
      significant increase in VapA-specific immunoglobulin (Ig) production, with total
      IgG and IgG(T) being increased by day 15. Expression of VapA-specific IFN-gamma
      mRNA by BAL cells was increased in the vaccinated foals following challenge.
      Postmortem lung severity scores did not differ between groups. Two foals shed
      virulent R. equi in feces; however, real-time polymerase chain reaction (PCR)
      revealed the isolates to be different from the challenge strain.

PMID- 24101792
TI  - Effect of treatment with a cationic antiviral compound on acute infection with
      bovine viral diarrhea virus.
AB  - Bovine viral diarrhea virus (BVDV) is a widespread bovine pathogen capable of
      causing disease affecting multiple body systems. Previous studies have shown 2-(2
      benzimidazolyl)-5-[4-(2-imidazolino)phenyl]furan dihydrochloride (DB772)
      effectively prevents BVDV infection in cell culture. The aim of this project was
      to assess the efficacy of DB772 for the prevention of acute BVDV infection. Four
      calves seronegative to BVDV were treated with DB772 and another 4 calves were
      treated with diluent only on the same dosing schedule. Each calf was subsequently
      challenged intranasally with BVDV. Virus was isolated consistently from untreated
      calves on days 4 to 8, while treated calves remained negative by virus isolation
      during this period. Azotemia was exhibited by all treated calves on day 4
      resulting in the euthanasia of 1 calf on day 10 and the death of another on day
      13. Virus was isolated from the 2 remaining treated calves on day 14 or 21. On
      day 21, both remaining treated calves and all 4 untreated calves had anti-BVDV
      antibody titers > 1:2048. This pilot study indicates that DB772 temporarily
      prevented acute disease due to BVDV, but carries a significant concern of renal
      toxicity. 

PMID- 24101793
TI  - Patient factors influencing the concentration of stromal vascular fraction (SVF)
      for adipose-derived stromal cell (ASC) therapy in dogs.
AB  - The objective of this study was to determine whether patient factors influence
      the concentration of the stromal vascular fraction (SVF) in fat for adipose
      derived stromal cell (ASC) therapy in dogs. A total of 1265 dogs underwent
      adipose collection surgeries by veterinarians for processing by the Vet-Stem
      laboratory and data on cell counts and patient factors were collected. Body
      condition score (BCS) and breed size did not significantly affect the viable
      cells per gram (VCPG) of adipose tissue that represents the viable SVF. Age
      significantly affected the VCPG, with dogs in age quartile 1 having a
      significantly higher VCPG than those in quartile 2 (P = 0.003) and quartile 4 (P
      = 0.002). Adipose tissue collected at the falciform location had significantly
      fewer VCPG than tissue collected at the thoracic wall and inguinal locations (P <
      0.001). When the interaction of gender and location was evaluated, there were
      significantly fewer VCPG in tissue collected at the falciform location than at
      the thoracic wall and inguinal locations in female spayed dogs (P < 0.001) and
      male neutered dogs (P < 0.001), but not in female intact dogs (P = 0.743) or male
      intact dogs (P = 0.208). It was concluded that specific patient factors should be
      taken into consideration in order to obtain the maximal yield of VCPG from an
      adipose collection procedure. 

PMID- 24101794
TI  - Program of vaccination and antibiotic treatment to control polyserositis caused
      by Haemophilus parasuis under field conditions.
AB  - The present study investigated the effects of vaccinating sows and piglets or
      piglets alone against Haemophilus parasuis on the prevalence of H. parasuis in
      nasal swabs, on the humoral and cellular immune responses, and on the production
      parameters of piglets at 3 Korean farms with a clinical history of polyserositis
      caused by H. parasuis. Piglets born to vaccinated or non-vaccinated sows were
      subdivided into 3 groups: vaccinated sows and vaccinated pigs (VS-VP), non
      vaccinated sows and vaccinated pigs (NVS-VP), and non-vaccinated sows and non
      vaccinated pigs (NVS-NVP). The proportion of piglets with positive nasal swabs
      was significantly lower (P < 0.05) in the vaccinated animals (VS-VP and NVS-VP
      groups) than in the non-vaccinated animals (NVS-NVP group) at 35 and 60 d of age
      at the 3 farms. The overall growth performance (from 7 to 60 d of age) of the
      vaccinated piglets was significantly better (P < 0.05) than that of the non
      vaccinated piglets at the 3 farms. Piglets in the VS-VP group had significantly
      higher levels (P < 0.05) of H. parasuis-specific IgG antibodies, lymphocyte
      proliferation, and interferon-gamma-secreting cells than piglets in the NVS-VP
      and NVS-NVP groups on days 1, 7, 21, 35, and 60 after birth at the 3 farms. 

PMID- 24101796
TI  - Comparison of histological lesions in mink with acute hemorrhagic pneumonia
      associated with Pseudomonas aeruginosa or Escherichia coli.
AB  - Hemorrhagic pneumonia can be a major cause of mortality in farmed mink in the
      fall. In its classic form, hemorrhagic pneumonia is caused by the bacterium
      Pseudomonas aeruginosa. In recent years, however, outbreaks of this type of
      pneumonia that are associated with hemolytic Escherichia coli have also occurred
      in farmed mink. The purpose of this study was to compare histological lesions of
      acute hemorrhagic pneumonia associated with both P. aeruginosa and E. coli in
      mink, including a description of tissue distribution of pathogens, in an attempt
      to differentiate between the 2 disease entities based on histopathology. The
      study included material submitted for diagnostic investigation to the National
      Veterinary Institute in Denmark from 2006 to 2009. Altogether, 19 cases of
      hemorrhagic pneumonia with a pure lung culture of P. aeruginosa and 18 cases of
      hemorrhagic pneumonia with a pure lung culture of E. coli were examined. Formalin
      fixed paraffin-embedded lung tissue obtained from the mink was examined by
      histology and fluorescence in-situ hybridization (FISH). It was possible to
      detect a slight histological difference between hemorrhagic pneumonia caused by
      P. aeruginosa and by E. coli, as P. aeruginosa was most often found surrounding
      blood vessels and lining the alveoli, while E. coli showed a more diffuse
      distribution in the lung tissue. Furthermore, P. aeruginosa often elicited a very
      hemorrhagic response in the lung, while infection with E. coli was associated
      with a higher frequency of alveolar edema and mild lymphoid cuffing in the lungs.

PMID- 24101797
TI  - Relationship of the extent of pulmonary lesions to the partial pressure of oxygen
      and the lactate concentration in arterial blood in calves experimentally infected
      with bovine respiratory syncytial virus.
AB  - Bovine respiratory syncytial virus (BRSV) is a primary agent of pneumonia in
      calves that causes damage to pulmonary epithelium and results in respiratory
      distress. This retrospective cumulative analysis of data from 681 calves
      experimentally infected with BRSV was undertaken to determine if there was an
      association of both the partial pressure of oxygen in arterial blood (PaO2) and
      the lactate concentration in arterial blood with lung lesion severity, as well as
      to estimate the potential predictive value of these 2 parameters in assessing
      disease progression. The PaO2 was highly significantly associated with the extent
      of lung lesions and was considered highly predictive of lesion severity. Although
      the arterial blood lactate concentration was also significantly associated with
      lung disease, the results were not consistent for all days after challenge. Also,
      the lactate level was usually within the reference interval. Thus, the usefulness
      of the arterial blood lactate concentration in predicting the course of BRSV
      associated pneumonia is limited in the clinical setting.

PMID- 24101795
TI  - Anti-inflammatory response of dietary vitamin E and its effects on pain and joint
      structures during early stages of surgically induced osteoarthritis in dogs.
AB  - There is evidence that vitamin E (VE) has anti-inflammatory and analgesic
      properties in human osteoarthritis (OA). This double-blinded and randomized pilot
      study used a broad spectrum of clinical and laboratory parameters to investigate
      whether such beneficial effects could be detected in a canine experimental OA
      model. Dogs were divided into 2 groups: control (n = 8), which received a
      placebo, and test group (n = 7), which received 400 IU/animal per day of VE for
      55 d, starting the day after transection of the cranial cruciate ligament.
      Lameness and pain were assessed using a visual analogue scale (VAS), numerical
      rating scale (NRS), and electrodermal activity (EDA) at day 0, day 28, and day
      55. Cartilage and synovial inflammation lesions were assessed. One-side
      comparison was conducted at an alpha-threshold of 10%. At day 56, dogs were
      euthanized and concentrations of prostaglandin E2 (PGE2), nitrogen oxides (NOx),
      and interleukin-1 beta (IL-1beta) were measured in synovial fluid. Concentrations
      of NOx and PGE2 in synovial fluid were lower in the test group (P < 0.0001 and P
      = 0.03, respectively). Values of VAS, NRS, and EDA showed a consistent trend to
      be lower in the test group than in the control, while statistical significance
      was reached for VAS at day 55 and for EDA at day 28 (adjusted P = 0.07 in both
      cases). Histological analyses of cartilage showed a significant reduction in the
      scores of lesions in the test group. This is the first time that a study in dogs
      with OA using a supplement with a high dose of vitamin E showed a reduction in
      inflammation joint markers and histological expression, as well as a trend to
      improving signs of pain. 

PMID- 24101798
TI  - Evaluation of a broad range real-time polymerase chain reaction (RT-PCR) assay
      for the diagnosis of septic synovitis in horses.
AB  - Septic synovitis is a potentially debilitating and life-threatening disorder in
      horses. We hypothesized that a universal bacterial real-time PCR (RT-PCR) assay
      would have improved sensitivity and decreased turn-around time for detection of
      bacteria in synovial fluid (SF) samples. Forty-eight SF samples were collected
      from 36 horses that presented to two referral institutions with suspected septic
      synovitis. Universal RT-PCR, bacterial culture and SF analysis were performed on
      all samples, and an interpretation on the sample being septic or not was derived
      by three board certified specialists from the history, clinical assessment and SF
      characteristics. RT-PCR results were compared to a composite standard comprised
      of positive culture and interpretation by all three specialists of samples as
      "septic". For 41 of 48 samples (85%), culture and RT-PCR results were concordant.
      Compared to the composite standard, 83% of samples were correctly classified by
      RT-PCR (turn-around time of approximately 4 hours). Relative sensitivity and
      specificity of RT-PCR were 87% and 72% respectively, and 56% and 86% for culture.
      Hence, universal RT-PCR was a rapid and highly sensitive test, which may
      accelerate diagnosis and improve outcome for horses with septic synovitis. 

PMID- 24101799
TI  - Estrus response and fertility after a single cloprostenol treatment in dairy cows
      with various ovarian structures.
AB  - The objective of this study was to determine rates of estrus and conception in
      lactating multiparous Holstein cows given 500 MUg of cloprostenol intramuscularly
      after detection of the following >= 60 d after parturition: a solid corpus luteum
      (CL), a CL with a nonechodense cavity <= 20 mm in diameter (CLcav), a luteal cyst
      (cavity > 20 mm in diameter and a luteinized wall > 3 mm in diameter), or a
      follicular cyst (cavity > 20 mm and a luteinized wall <= 3 mm in diameter). The
      estrus rates were 335/419 (80.0%), 183/223 (82.1%), 170/182 (93.4%), and 44/87
      (50.6%), respectively (P < 0.0001), and the conception rates 30 to 36 d after
      insemination among the estrous cows with an apparently normal mucus discharge
      were 130/285 (45.6%), 44/141 (31.2%), 39/79 (49.4%), and 19/30 (63.3%),
      respectively (P < 0.002). Compared with a solid CL, a CLcav did not affect the
      estrus rate but significantly reduced the conception rate (P < 0.05), and the
      estrus rates were significantly higher and lower in cows with a luteal or
      follicular cyst, respectively (P < 0.05). 

PMID- 24101800
TI  - Effect of infectious dose and season on development of hemorrhagic pneumonia in
      mink caused by Pseudomonas aeruginosa.
AB  - Hemorrhagic pneumonia is an acute and fatal disease of farmed mink caused by
      Pseudomonas aeruginosa. The pathogenesis of this disease has not yet been
      resolved. Mink are the only animals known to be susceptible to acute, contagious,
      and fatal lung infections caused by P. aeruginosa. The purpose of this study was
      to investigate the correlation between dose-response and season of infection and
      to clarify whether Danish mink are carriers of P. aeruginosa on their nasal
      mucosa during the season for hemorrhagic pneumonia. To elucidate the pathogenesis
      of the disease, an infectious dose-response trial was carried out on adult mink
      and mink kits, both in the season for hemorrhagic pneumonia (November) as well as
      out of season (July). It proved difficult to infect mink via the intra-nasal
      route. Only 4 out of 60 infected mink developed clinical disease and were
      euthanized, all of them in November, illustrating that predisposing factors in
      the mink itself and not infectious dose might be crucial for disease development.
      We were able to culture P. aeruginosa from the nasal cavity of the clinically
      healthy experimental mink 8 d after inoculation. This indicated that the mink can
      carry P. aeruginosa on their nasal mucosa without developing the disease. It was
      not possible, however, to culture P. aeruginosa from the nasal cavity of
      clinically healthy mink obtained from farms in November, which indicates that the
      organism is not a normal part of the nasal mucosal flora of mink. 

PMID- 24101801
TI  - Changes in leukocyte populations of cows with milk fever or displaced abomasum
      after calving.
AB  - Most of the metabolic diseases of dairy cows occur within the first 2 wk after
      calving, and cows with a metabolic disease are prone to infectious diseases.
      Although metabolic diseases are generally recognized as a risk factor for
      infectious diseases owing to the associated decrease in immune function, the
      difference in immune status between cows with milk fever (MF) or displaced
      abomasum (DA) during the lactation period has not been clarified. Therefore, the
      peripheral blood leukocyte populations in 38 multiparous Holstein cows from 1
      herd were analyzed after calving. The cows were divided into 3 groups according
      to health: 21 cows that remained clinically healthy throughout the experimental
      period (control group), 9 cows that had MF on the day of calving, and 8 cows with
      an onset of DA within 4 wk after calving. The T- and B-cell numbers were lowest
      at week 0, and they increased gradually after calving. There was no significant
      difference between the 3 groups in the number of each subset of leukocytes on the
      day of calving, but the number of CD8+ T-cells was significantly lower in the MF
      and DA groups than in the control group at week 1. The numbers of CD4+, CD8+, and
      WC1+ T-cells tended to be lower in the DA group than in control group from weeks
      4 to 12, a tendency not observed in the MF group. These data suggest that when
      cows have DA around the time of calving, their lymphocyte numbers remain lower
      until 12 wk after calving.

PMID- 24101802
TI  - Thromboelastography platelet mapping in healthy dogs using 1 analyzer versus 2
      analyzers.
AB  - The objective of this study was to describe the results of thromboelastography
      platelet mapping (TEG-PM) carried out using 2 techniques in 20 healthy dogs.
      Maximum amplitudes (MA) generated by thrombin (MAthrombin), fibrin (MAfibrin),
      adenosine diphosphate (ADP) receptor activity (MAADP), and thromboxane A2 (TxA2)
      receptor activity (stimulated by arachidonic acid, MAAA) were recorded.
      Thromboelastography platelet mapping was carried out according to the
      manufacturer's guidelines (2-analyzer technique) and using a variation of this
      method employing only 1 analyzer (1-analyzer technique) on 2 separate blood
      samples obtained from each dog. Mean [+/- standard deviation (SD)] MA values for
      the 1-analyzer/2-analyzer techniques were: MAthrombin = 51.9 mm (+/- 7.1)/52.5 mm
      (+/- 8.0); MAfibrin = 20.7 mm (+/- 21.8)/23.0 mm (+/- 26.1); MAADP = 44.5 mm (+/-
      15.6)/45.6 mm (+/- 17.0); and MAAA = 45.7 mm (+/- 11.6)/45.0 mm (+/- 15.4). Mean
      (+/- SD) percentage aggregation due to ADP receptor activity was 70.4% (+/-
      32.8)/67.6% (+/- 33.7). Mean percentage aggregation due to TxA2 receptor activity
      was 77.3% (+/- 31.6)/78.1% (+/- 50.2). Results of TEG-PM were not significantly
      different for the 1-analyzer and 2-analyzer methods. High correlation was found
      between the 2 methods for MAfibrin [concordance correlation coefficient (r) =
      0.930]; moderate correlation was found for MAthrombin (r = 0.70) and MAADP (r =
      0.57); correlation between the 2 methods for MAAA was lower (r = 0.32).
      Thromboelastography platelet mapping (TEG-PM) should be further investigated to
      determine if it is a suitable method for measuring platelet dysfunction in dogs
      with thrombopathy. 

PMID- 24101803
TI  - Efficacy of a piglet-specific commercial inactivated vaccine against Porcine
      circovirus type 2 in clinical field trials.
AB  - The efficacy of a piglet-specific inactivated Porcine circovirus type 2 (PCV2)
      vaccine was evaluated with clinical field trials, as recommended by the Republic
      of Korea's Animal, Plant & Fisheries Quarantine & Inspection Agency. Three farms
      were selected on the basis of their history of postweaning multisystemic wasting
      syndrome. On each farm 60, 1-week-old pigs were randomly allocated to 1 of 2
      treatment groups: vaccination at 1 and 3 wk of age or no vaccination. The 2-dose
      schedule of vaccination with inactivated PCV2 vaccine improved the average daily
      weight gain from birth to 16 wk of age, the PCV2 load in the blood, and the
      frequency and severity of lymph node lesions. Inactivated PCV2 vaccine seems to
      be very effective in controlling PCV2 infection under field conditions. 

PMID- 24101805
TI  - Striatal toe.
AB  - We report a case of striatal toe in an adolescent with an infarct in lentiform
      nucleus and briefly discuss its differential diagnoses. 

PMID- 24101804
TI  - An update on Spino-cerebellar ataxias.
AB  - The dominantly inherited ataxias, also known as Spino-cerebellar ataxias (SCAs),
      are rapidly expanding entities. New mutations are being identified at remarkable
      regularity. Recent awareness of molecular abnormalities in SCAs has addressed
      some of the long sought questions, but gaps in knowledge still exist. Three major
      categories of SCAs, according to molecular mechanisms, have evolved over recent
      few years: Polyglutamate expansion ataxia, non-coding zone repeat ataxia, and
      ataxia due to conventional mutation. Using the fulcrum of these mechanisms, the
      article provides an update of SCAs. Shared and specific clinical features,
      genetic abnormalities, and possible links between molecular abnormalities and
      cerebellar degeneration have been discussed. Emphasis has been placed on the
      mechanisms of polyglutamate toxicity. 

PMID- 24101806
TI  - Neuropsychological aspects of clinical neurology: A glimpse of two universes in
      brain.

PMID- 24101807
TI  - A literature review of AD7c-ntp as a biomarker for Alzheimer's disease.
AB  - The cornerstone of diagnosis of Alzheimer's disease (AD) is still the clinical
      criteria for probable and possible AD established by the NINCDS-ADRDA Work Group
      in 1984, which had survived for over 27 years. However, with the increase in
      people's knowledge of clinical manifestations and biology of AD, this standard is
      gradually proving to be insufficient; the early diagnosis of AD is thus
      particularly important. Therefore, in 2011, the National Institute on Aging and
      the Alzheimer's Association revised the criteria and integrated biomarker
      evidence into it. Biomarker evidence is expected to enhance the
      pathophysiological specificity of the diagnosis of AD. According to Consensus
      Report of the Working Group on Molecular and Biochemical Markers of Alzheimer's
      Disease, a qualified biomarker for AD should have the following abilities: It
      should detect a fundamental feature of neuropathology and be validated in
      neuropathologically confirmed cases, reliably with an sensitivity >80% for
      detecting AD and a specificity >80% for distinguishing other dementias; be
      reproducible and non-invasive; and be simple to perform and inexpensive.
      Alzheimer-associated neuronal thread protein (AD7c-NTP) is a member of "neuronal
      thread proteins" (NTPs); it can be detected in increased concentration in
      cortical neurons, brain-tissue extracts, cerebrospinal fluid, and urine in the
      early course of AD neurodegeneration, and it level is proportional to the degree
      of dementia, which makes it a promising biomarker for AD. In this review, we have
      evaluated the feasibility of developing AD7c-NTP as a biomarker for AD. 

PMID- 24101808
TI  - Mild cognitive impairment in adult: A neuropsychological review.
AB  - Mild cognitive impairment (MCI) is associated with an increased risk of
      developing dementia. This is clinically relevant overt dementia can be prevented
      if treatment strategies are devised for MCI. Neuropsychological deficits in this
      condition are very common and are important clinically for treatment and
      outcomes. We aimed to review various neuropsychological deficits in MCI. Further,
      we have presented the current evidence for nosological status, neuroanatomical
      basis, and clinical outcome of this heterogeneous construct. All published papers
      on the topic of neuropsychological deficits in MCI on Medline and other databases
      were reviewed. A wide range of memory and executive function deficits are common
      in MCI patients. However, several studies are limited by either improper designs
      or inadequate sample sizes. Several neuropsychological impairments like memory
      function and executive functions can be diagnosed in MCI. The evidence base for
      the exact neuroanatomical basis of MCI is not robust yet. However, given the wide
      range of outcomes, controversies and debates exist regarding the nosological
      significance of the deficits. Hence, more studies are needed to specifically
      locate the impairments and further delineate the construct of MCI. 

PMID- 24101809
TI  - Outcomes of neuropsychological interventions of stroke.
AB  - The reported prevalence of cognitive deficits within the first month of stroke
      ranges widely from 10% to 82%, depending primarily on the criteria used to define
      cognitive impairment and on the selected patient population. These cognitive
      defects progress toward impairment over a course of time if left untreated. Among
      the most common cognitive deficits are the attentional, the visuoperceptual, the
      memory and executive function deficits. As these impairments are being
      increasingly recognized in the scientific communities, more and more studies are
      being devoted to the outcomes of various therapies for these disorders. In this
      review, we focus on the outcomes of various therapies for these cognitive
      disorders over time. We reviewed all the possible medical databases using key
      words for individual cognitive deficit treatment outcomes. All the possible
      studies including randomized controlled trials, pre-post design studies, case
      series and single case reports were included in this study. On the basis of
      present literature review, we conclude that the evidence is definitively positive
      only for outcomes of attentional and visuoperceptive skill deficits. On the other
      hand, there have been very few studies to conclude for effectiveness of various
      therapies for memory and executive function outcomes. 

PMID- 24101810
TI  - Heart rate and blood pressure variability in patients with myasthenia gravis.
AB  - This cross-sectional case control study included subjects aged between 18 and 65
      years with diagnosis of myasthenia gravis (MG) in Osserman's Stage I and Stage
      IIa and those in remission with positive and negative acetylcholine receptor
      antibody (AChRAb). They were evaluated for heart rate variability (HRV) and other
      conventional autonomic functions. Patients with co-morbidities that can affect
      autonomic nervous system were excluded. Repetitive nerve stimulation test (RNST),
      nerve conduction test, AChRAb assay, and computerized tomography (CT) of chest
      were done in all the patients. All patients of MG who fulfilled the inclusion
      criteria had a minimum drug-free period of 6 h which was followed by HRV and
      other conventional tests. Thirty subjects fulfilling study criteria and an equal
      number of age and gender-matched healthy subjects were enrolled as controls.
      Autonomic function tests revealed significant changes in HRV (both time and
      frequency domain) parameters suggestive of parasympathetic deficiency as well as
      shifting of sympathovagal balance towards raised sympathetic tone. With regards
      to conventional autonomic function tests, there was statistically significant
      decrease in values of heart rate-based tests as well as blood pressure-based test
      (isometric handgrip test) in study group compared with controls, again indicative
      of significant parasympathetic deficiency and minimal sympathetic deficiency. We
      conclude that in MG, cholinergic transmission is affected more diffusely than
      previously thought. 

PMID- 24101811
TI  - A cross-sectional study on thyroid status in North Indian elderly outpatients
      with dementia.
AB  - BACKGROUND: Several population based studies have demonstrated an association
      between hypo-or hyperthyroidism and dementia in last two decades. As a
      consequence, thyroid stimulating hormone has become part of the screening
      laboratory test for dementia. AIM: The aim of the present study was to evaluate
      the association between thyroid function and Alzheimer's disease (AD) and
      vascular dementia (VaD) and to determine the risk of AD and VaD in clinically
      euthyroid patients. MATERIALS AND METHODS: A cross-sectional hospital based study
      was carried out in subjects diagnosed with AD/VaD and were assessed for thyroid
      status as routine screening test. RESULTS: Free T3, free T4 and TSH were studied
      in 114 AD patients (mean age: 65 years), 35 VaD patients (mean age: 62 years) and
      105 control subjects (mean age: 62 years). In AD group, TSH levels were
      significantly lower than controls (P = 0.00) and for each unit increase in TSH
      level, the odds of having dementia decreased by 37.1%. No such relation was seen
      in VaD. CONCLUSION: The results suggest a consistent association of subclinical
      hyperthyroidism and AD.

PMID- 24101812
TI  - Congenital myasthenic syndromes: Natural history and long-term prognosis.
AB  - INTRODUCTION: Congenital myasthenia syndrome (CMS) is a rare, heterogeneous group
      of genetically determined, disorder of neuromuscular transmission. They have a
      varied presentation and progression and very few studies have addressed the
      natural history. Aim of the present study is to describe the clinical profile and
      natural history of patients with CMS. MATERIALS AND METHODS: Study includes
      patients with CMS who attended comprehensive-neuromuscular-clinic (CNMC) during
      the period January, 2000-2008 with a minimum follow-up of 2 years, with inclusion
      criteria: (1) Onset in infancy or childhood with fluctuating ocular, bulbar,
      respiratory or limb muscle weakness (2) Acetylcholine receptor antibody negative
      (3) normal computed tomography (CT) thymus (4) Abnormal repetitive nerve
      stimulation (RNS) testing (5) Exclusion of other autoimmune disorders. RESULTS:
      Out of 314 patients with myasthenia who attended the CNMC during study period, 15
      (4.8%) were with CMS (8 boys, 7 girls). Patients were divided as infantile and
      childhood onset. The mean age of onset and diagnosis in infantile and childhood
      onset groups were 5.5 months/3.1 years and 3.6 years/6.5 years respectively.
      Eleven patients had ptosis and 4 had generalized presentation. Most common site
      of decremental response was over facial nerve in 12 (75%) patients. All patients
      showed good response to treatment with acetyl cholinesterase inhibitor with
      stable course on follow-up without exacerbations. Mean dose for neostigmine was
      28 mg/day and for pyridostigmine was 153 mg/day. CONCLUSION: Ptosis is most
      common symptom at onset in CMS, emphasing importance of RNS of the facial nerve,
      in the absence of molecular diagnosis of CMS. Our CMS cohort had relatively
      stable course without intermittent exacerbations with fair response to acetyl
      cholinesterase inhibitor.

PMID- 24101813
TI  - Effects of oral motor therapy in children with cerebral palsy.
AB  - AIM: Oral motor dysfunction is a common issue in children with cerebral palsy
      (CP). Drooling, difficulties with sucking, swallowing, and chewing are some of
      the problems often seen. In this study, we aimed to research the effect of oral
      motor therapy on pediatric CP patients with feeding problems. MATERIALS AND
      METHODS: Included in this single centered, randomized, prospective study were 81
      children aged 12-42 months who had been diagnosed with CP, had oral motor
      dysfunction and were observed at the Pediatric Neurology outpatient clinic of the
      Children's Health and Diseases Department, Istanbul Medical Faculty, Istanbul
      University. Patients were randomized into two groups: The training group and the
      control group. One patient from the training group dropped out of the study
      because of not participating regularly. Following initial evaluation of all
      patients by a blinded physiotherapist and pedagogue, patients in the training
      group participated in 1 h oral motor training sessions with a different
      physiotherapist once a week for 6 months. All patients kept on routine
      physiotherapy by their own physiotherapists. Oral motor assessment form,
      functional feeding assessment (FFA) subscale of the multidisciplinary feeding
      profile (MFP) and the Bayley scales of infant development (BSID-II) were used to
      evaluate oral motor function, swallowing, chewing, the gag reflex, the
      asymmetrical tonic neck reflex, tongue, jaw, and mouth function, severity of
      drooling, aspiration, choking, independent feeding and tolerated food texture
      during the initial examination and 6 months later. RESULTS: When the initial and
      post-therapy FFA and BSID-II scores received by patients in the training and the
      study group were compared, the training group showed a statistically significant
      improvement (P < 0.05). CONCLUSION: Oral motor therapy has a beneficial effect on
      feeding problems in children with CP.

PMID- 24101814
TI  - Pattern of seizure cases in tertiary care hospitals in Karnataka state of India.
AB  - BACKGROUND: The prevalence and incidence of epilepsy is higher in developing
      countries than in developed countries. Understanding pattern and risk factors of
      seizure cases will help in suggesting appropriate preventive measures.
      OBJECTIVES: This study was carried out to assess the pattern of seizure, its
      management and compliance with treatment. MATERIALS AND METHODS: Data from
      medical records of seizure cases in three tertiary care hospitals of Mangalore
      city in south India admitted from January 2006 to December 2011 were collected
      and analyzed. RESULTS: Nearly half (44.4%) of the 196 cases belonged to
      productive age group (15-45 years) and 2/3(rd) (60.7%) were males. Majority (>80%
      cases) were unskilled workers and of low socio-economic status groups. Family
      history of seizures was present in 8.4% cases. Mean age of onset of seizure was
      found to be 19.9 years. Proportion of generalized tonic clonic seizure cases was
      78.1%. Secondary seizures were seen in 66 (33.7%) cases with the most common
      cause being trauma to the head (24.2%). Refractory seizures were present in 2.7%
      cases. Monotherapy was the most commonly followed treatment regimen and phenytoin
      was the most popular anti-epileptic drug (AED) used. Non-compliance with AEDs was
      seen in 18.1% cases and was more among patients on polytherapy (P = 0.032).
      CONCLUSION: Seizure manifestations and treatment compliance vary widely in the
      studied population. In depth analysis of each seizure type will give more
      information about the factors associated with it.

PMID- 24101815
TI  - Clinico - diagnostic and therapeutic relevance of computed tomography scan of
      brain in children with partial seizures.
AB  - BACKGROUND: Therapeutic relevance of computed tomography (CT) in children with
      partial seizures is reported to be remarkably low (1-2%). However, in the
      developing countries where infections involving the nervous system are common,
      routine CT scan of brain may help in finding treatable causes of seizures.
      OBJECTIVE: Aim of this study was to evaluate the significance of CT scan of brain
      in the management of children with partial seizures. MATERIALS AND METHODS:
      Children with partial epilepsy, whose predominant seizure type was focal motor
      seizures, were included in the study. CT scan of brain was done in all children
      aged between 1 month and 12 years with partial seizures of unknown etiology
      prospectively. The clinical findings of these children were noted along with the
      CT findings. RESULTS: Between August 2001 and July 2002, of the 200 children with
      seizure disorder 50 children who satisfied the inclusion criteria were included
      in the study. CT scan of brain was normal in 16 children (32%) and was abnormal
      in 34 children (68%). Twenty children (~60% of abnormal scan) had potentially
      correctable lesions: Tuberculoma (n = 13), neurocysticercosis (n = 3), and brain
      abscess (n = 4). Five children had changes representing static pathology that did
      not influence patient management. The clinical features correlated with CT
      findings in 78% children. CONCLUSION: Children with partial motor seizures have
      high probability of having abnormal findings on CT scan of brain, especially,
      neuro-infections which are potentially treatable. Therefore, CT scan brain should
      be carried out in all children with partial motor seizures especially, in
      developing countries.

PMID- 24101817
TI  - Stroke and aphasia quality of life scale in Kannada-evaluation of reliability,
      validity and internal consistency.
AB  - BACKGROUND: Quality of life (QoL) dwells in a person's overall well-being.
      Recently, QoL measures have become critical and relevant in stroke survivors.
      Instruments measuring QoL of individuals with aphasia are apparently rare in the
      Indian context. The present study aimed to develop a Kannada instrument to
      measure the QoL of people with aphasia. Study objectives were to validate Stroke
      and aphasia quality of life-39 (SAQOL-39) into Kannada, to measure test-retest
      reliability and internal consistency. MATERIALS AND METHODS: The original English
      instrument was modified considering socio-cultural differences among native
      English and Kannada speakers. Cross-linguistic adaptation of SAQOL-39 into
      Kannada was carried out through forward-backward translation scheme. The scale
      was administered on 32 people from Karnataka (a state in India) having aphasia.
      For a direct understanding of the subject's QoL, scores were categorized into QoL
      severity levels. Item reliability of the Kannada version was examined by
      measuring Cronbach's alpha. Test-retest reliability was examined by calculating
      the intraclass correlation coefficient (ICC). RESULTS: Kannada SAQOL-39 showed
      good acceptability with minimum missing data and excellent test-retest
      reliability (ICC = 0.8). Value of Cronbach's alpha observed for four items
      modified in the original version was 0.9 each and the mean alpha of all Kannada
      items was 0.9, demonstrating high internal consistency. CONCLUSIONS: The present
      study offers a valid, reliable tool to measure QoL in Kannada-speaking
      individuals with aphasia. This tool is useful in a cross-center, cross-national
      comparison of QoL data from people with aphasia. This instrument also permits
      direct translation into other Indian languages as the items are culturally
      validated to the Indian population. This study promotes future research using the
      Kannada SAQOL-39.

PMID- 24101816
TI  - Pathway to care of epilepsy patients: Exploratory study from an urban slum in
      Northern India.
AB  - INTRODUCTION: Epilepsy is a chronic neurological disorder with major psychosocial
      correlates. Most epilepsy patients in developing countries are untreated or
      inadequately treated. It is essential to understand the pathway, to care taken by
      epilepsy patients in a community, to be able to target appropriate services to
      them. MATERIALS AND METHODS: A community based study was conducted on all
      epilepsy patients in an urban slum in Northern India to study their pathways to
      care. A list of persons suffering from epilepsy was generated by house to house
      visits, snowballing, and key informant contacts. In-depth interview and Medical
      Record Review were used to document their pathway to care. RESULTS: Thirteen of
      the twenty two patients had contacted a health-care provider for their first
      episode. The most common first link of care for the patients was secondary level
      Government hospitals. The next common was private practitioners, followed by
      Tertiary Care Hospitals, and registered medical practitioners. Eleven out of
      twenty two patients had to contact a Tertiary Level Center for seeking care. The
      number of health-care facilities consulted before arriving at their latest point
      of care ranged from 0 to 5. Traditional or faith healers were consulted at some
      point of time for cure. CONCLUSION: There is a need to focus on strengthening and
      capacity building of the primary care settings for managing epilepsy to enable
      their better utilization. This shall prevent unnecessary referrals and hence the
      load on the already burdened higher facilities.

PMID- 24101818
TI  - Etiological spectrum of hypokalemic paralysis: A retrospective analysis of 29
      patients.
AB  - BACKGROUND: Hypokalemic paralysis is characterized by episodes of acute muscle
      weakness associated with hypokalemia. In this study, we evaluated the possible
      etiological factors in patients of hypokalemic paralysis. MATERIALS AND METHODS:
      We reviewed the records of 29 patients who were admitted with a diagnosis of
      hypokalemic paralysis. Modified Guillain-Barre' Syndrome disability scale was
      used to grade the disability. RESULTS: In this study, 15 (51.7%) patients had
      secondary causes of hypokalemic paralysis and 14 patients (42.3%) had idiopathic
      hypokalemic paralysis. Thyrotoxicosis was present in six patients (20.6%), dengue
      infection in four patients (13.7%), distal renal tubular acidosis in three
      patients (10.3%), Gitelman syndrome in one patient (3.4%), and Conn's syndrome in
      one patient (3.4%). Preceding history of fever and rapid recovery was seen in
      dengue infection-induced hypokalemic paralysis. Approximately 62% patients had
      elevated serum creatinine phosphokinase. All patients had recovered completely
      following potassium supplementation. Patients with secondary causes were older in
      age, had significantly more disability, lower serum potassium levels, and took
      longer time to recover. CONCLUSION: In conclusion, more than half of patients had
      secondary causes responsible for hypokalemic paralysis. Dengue virus infection
      was the second leading cause of hypokalemic paralysis, after thyrotoxicosis.
      Presence of severe disability, severe hypokalemia, and a late disease onset
      suggested secondary hypokalemic paralysis.

PMID- 24101820
TI  - Neuromyelitis optica-IgG testing in an Indian cohort with neuromyelitis optica
      and related demyelinating disorders: Our experience.
AB  - BACKGROUND: Neuromyelitis optica (NMO) is an immune-mediated inflammatory
      demyelinating disorder of the central nervous system with a predilection for the
      optic nerves and the spinal cord. Immunopathological evidence suggests that the
      target antigen of the disease is aquaporin-4. An IgG antibody against this
      protein has been explored as a molecular marker for the disease and as a
      diagnostic tool due to its high sensitivity and specificity in various
      populations. OBJECTIVE: To assess the value of NMO-IgG testing in Indian patients
      with clinical and magnetic resonance imaging features consistent with NMO and
      longitudinally extensive transverse myelitis (LETM). MATERIALS AND METHODS: Forty
      five patients with clinical and magnetic resonance imaging features consistent
      with NMO, LETM, and MS were tested for serum NMO-IgG. Of these patients, 22
      patients satisfied revised (2006) Wingerchuk criteria for NMO (excluding NMO-IgG
      status) and 11 patients had LETM. Twelve patients satisfied the revised (2010)
      McDonald criteria for multiple sclerosis (MS). RESULTS: Of the 21 patients,
      satisfying the criteria for NMO and for whom the test results were available, 17
      were positive for NMO-IgG (80.9%), and of the 11 patients having LETM, 6 (54.5%)
      were positive for NMO-IgG. In one patient with NMO, the test result was not
      available. None of the 12 patients satisfying McDonald criteria for MS showed NMO
      IgG seropositivity. CONCLUSION: Our study suggests that it is worthwhile to
      pursue NMO-IgG testing as a diagnostic tool for patients with clinical and
      Magnetic Resonance Imaging (MRI) features consistent with NMO and LETM in the
      Indian population.

PMID- 24101819
TI  - Early language development in Indian children: A population-based pilot study.
AB  - OBJECTIVES: To study the prevalence of language delay and to examine its socio
      economic correlates in children less than 3 years. MATERIALS AND METHODS:
      Participants were 130 children (males = 56%) aged 12-35 months (mean age = 1.81
      years, SD = 0.58), from an urban center in north India. The language quotient
      (LQ) of the child was measured by the Clinical Linguistic Auditory Milestone
      Scale (CLAMS). Children with an LQ score of less than 70 were considered language
      delayed. RESULTS: Overall, 6.2% of the children were language delayed with a
      higher prevalence found for girls (7%) than for boys (5.5%), although the
      difference was not statistically significant. Several significant correlations
      between socio-economic and demographic variables and the LQ of the child were
      found. Stepwise multiple regression analysis revealed that 31.4% of the variance
      in the LQ scores of girls was accounted for by income (F = 23.80, P = 0.000) and
      18.1% of the variance in the LQ scores of boys was accounted for by education of
      the mother and income (F = 15.67, P = 0.000). CONCLUSIONS: Developmental problems
      in early years are often precursors of problems in later life and early
      intervention can facilitate favorable outcomes among children with multiple
      risks. The high prevalence of language difficulties in young children underscores
      the need to target language delay in early years, to reduce the likelihood of
      adverse outcomes and thus optimize chances of improvement.

PMID- 24101821
TI  - Association of intercellular adhesion molecular-1 gene polymorphism in ischemic
      stroke patients.
AB  - BACKGROUND: Ischemic stroke (IS) is a prevalent disease causing a body
      disability, the third leading cause of death in Taiwan. It shows that the level
      of intercellular adhesion molecular-1 (ICAM-1) in IS patients is higher than
      control subjects. OBJECTIVE: This study is to investigate the possible
      association of ICAM-1 (G1548A) polymorphism in IS patients. MATERIALS AND
      METHODS: A total of 646 subjects were enrolled in this study, including 312 IS
      patients, and 334 controls without a history of symptomatic IS. The ICAM-1
      (G1548A) polymorphism was analyzed by polymerase chain reaction and restriction
      fragment length polymorphism. Clinical factors were also determined. RESULTS: The
      frequencies of the ICAM-1 (G1548A) polymorphism for G/G, G/A, and A/A were 74.8%,
      23.9%, and 0.3%, respectively, in healthy controls, and 62.8%, 32.1%, and 5.1%,
      respectively, in patients. The frequency of the ICAM-1 (G1548A) A allele (21.2%
      versus 13.2%, respectively; P = 0.007) and the carriers of the ICAM-1 (G1548A) A
      allele (37.2% versus 25.2%; P = 0.019, OR 1.76, 95% CI 1.1-2.83) are great in IS
      patients compared with healthy controls. There is a higher risk of IS associated
      with homozygosity for the ICAM-1 (G1548A) A allele (AA genotype) compared with
      the control population (5.1% vs. 0.3%, respectively, P = 0.04; OR 5.1, 95% CI
      1.19-21.66). We also observed both hypertension and diabetes has shown a positive
      association with IS. CONCLUSIONS: The ICAM-1 (G1548A) polymorphism was associated
      with independent risk factor for the development of IS.

PMID- 24101822
TI  - Usefulness of medial temporal lobe atrophy visual rating scale in detecting
      Alzheimer's disease: Preliminary study.
AB  - BACKGROUND: The Korean version of Mini-Mental Status Examination (K-MMSE) and the
      Korean version of Addenbrooke Cognitive Examination (K-ACE) have been validated
      as quick neuropsychological tests for screening dementia in various clinical
      settings. Medial temporal atrophy (MTA) is an early pathological characteristic
      of Alzheimer's disease (AD). We aimed to assess the diagnostic validity of the
      fusion of the neuropsychological test and visual rating scale (VRS) of MTA in AD.
      MATERIALS AND METHODS: A total of fifty subjects (25 AD, 25 controls) were
      included. The neuropsychological tests used were the K-MMSE and the K-ACE. T1
      axial imaging visual rating scale (VRS) was applied for assessing the grade of
      MTA. We calculated the fusion score with the difference of neuropsychological
      test and VRS of MTA. The receiver operating characteristics (ROC) curve was used
      to determine optimal cut-off score, sensitivity and specificity of the fusion
      scores in screening AD. RESULTS: No significant differences in age, gender and
      education were found between AD and control group. The values of K-MMSE, K-ACE,
      CDR, VRS and cognitive function test minus VRS were significantly lower in the AD
      group than control group. The AUC (Area under the curve), sensitivity and
      specificity for K-MMSE minus VRS were 0.857, 84% and 80% and for K-ACE minus VRS
      were 0.884, 80% and 88%, respectively. Those for K-MMSE only were 0.842, 76% and
      72% and for K-ACE only were 0.868, 80% and 88%, respectively. CONCLUSIONS: The
      fusion of the neuropsychological test and VRS suggested clinical usefulness in
      their easy and superiority over neuropsychological test only. However, this study
      failed to find any difference. This may be because of small numbers in the study
      or because there is no true difference.

PMID- 24101823
TI  - A combined approach of bedside clinical examination and flexible endoscopic
      evaluation of swallowing in poststroke dysphagia: A pilot study.
AB  - BACKGROUND: As with most neurologic conditions, stroke involves impairment of the
      swallowing mechanism. This could be a spectrum of issues, the worst of which is
      aspiration. At the same time, the prolonged presence of a naso-gastric tube (NGT)
      has its own morbidity. Flexible endoscopic evaluation of swallowing (FEES) is one
      reliable method to assess the structural and functional status of the oropharynx
      and larynx, during the swallowing process. OBJECTIVE: To study the utility of
      FEES in decision-making with respect to resumption of oral intake in stroke
      patients. To document the findings of FEES in stroke patients, and to look for
      correlations between these and the site of stroke. MATERIALS AND METHODS:
      Protocol insertion of naso-gastric tube in all stroke patients, at presentation.
      Initial assessment by a neurologist and swallowing therapist, depending on
      cognitive status of the patient. All patients underwent MRI Brain with diffusion
      weighted sequences. After detailed clinical examination, they underwent swallow
      exercises under the supervision of a trained swallowing therapist. The decision
      to remove NGT was taken clinically by the combined decision of neurologist and
      swallowing therapist. Then all patients underwent FEES by the ENT surgeon. The
      final decision for NGT removal was taken as per the FEES findings. RESULT:
      Sixteen stroke patients underwent the FEES procedure during a period of six
      months. The oropharyngeal and laryngeal findings varied depending on the area of
      stroke involvement. Of these, change in decision regarding swallowing
      rehabilitation or NGT removal was needed in four patients, following the FEES
      findings. CONCLUSIONS: FEES is an easy, efficient and reliable method to evaluate
      the swallowing status in stroke patients. In combination with good bedside
      clinical examination and swallow exercises, it can be a good tool in assessing
      patients with post- stroke dysphagia. Post-stroke rehabilitation and prevention
      of aspiration pneumonia can be effectively done with the help of FEES.

PMID- 24101824
TI  - Evaluation of the motor cortical excitability changes after ischemic stroke.
AB  - BACKGROUND: We evaluated progressive changes in excitability of motor cortex
      following ischemic stroke using Transcranial Magnetic Stimulation (TMS).
      MATERIALS AND METHODS: Thirty-one patients (24 men, 7 women; age 37.3 +/- 8.2
      years) were recruited and TMS was performed using Magstim 200 stimulator and a
      figure-of-eight coil. Resting motor threshold (RMT) was recorded from affected
      and unaffected hemispheres and motor evoked potential (MEP) was recorded from
      contralateral FDI muscle. Central motor conduction time (CMCT) was calculated
      using F wave method. All measurements were done at baseline (2(nd)), 4(th), and
      6(th) week of stroke. RESULTS AFFECTED HEMISPHERE: MEP was recordable in 3
      patients at baseline (all had prolonged CMCT). At 4 weeks, MEP was recordable in
      one additional patient and CMCT remained prolonged. At 6 weeks, CMCT normalized
      in one patient. RMT was recordable (increased) in 3 patients at baseline, in one
      additional patient at 4 weeks, and reduced marginally in these patients at 6
      weeks. UNAFFECTED HEMISPHERE: MEP was recordable in all patients at baseline, and
      reduced significantly over time (2(nd) week 43.52 +/- 9.60, 4(th) week 38.84 +/-
      7.83, and 6(th) week 36.85 +/- 7.27; P < 0.001). The CMCT was normal and remained
      unchanged over time. CONCLUSION: The increase in excitability of the unaffected
      motor cortex suggests plasticity in the post-stroke phase.

PMID- 24101825
TI  - Giant racemose neurocysticercosis with mass effect: Unusual presentation.

PMID- 24101826
TI  - Intractable nausea and vomiting as presenting manifestation of neuromyelitis
      optica.

PMID- 24101827
TI  - Aortic saddle embolism and paraplegia due to a large left ventricular thrombus.

PMID- 24101828
TI  - Bilateral hypertrophic olivary degeneration.

PMID- 24101829
TI  - Hot cross bun sign in a patient with cerebellar ataxia.

PMID- 24101830
TI  - Myopathy with normal creatinine phosphokinase in a young man.

PMID- 24101831
TI  - Adductor laryngeal breathing dystonia in NBIA treated with botulinum toxin-A.
AB  - We report a rare case of neurodegeneration with brain iron accumulation (NBIA)
      presented with episodic inspiratory stridor. A 10-year-old boy presented with 3
      year history of gradually progressive spastic gait and generalized dystonia
      (involving all four limbs, neck, jaw, and speech). MRI brain showed "Eye of
      Tiger" sign. He recently developed severe inspiratory stridor associated with
      almost gasping respiration. Direct video laryngoscopy showed paradoxical vocal
      cord closure during inspiration. He was treated with EMG-guided botulinum toxin-A
      injection given into bilateral thyroarytenoid muscles, resulting in dramatic
      response with complete disappearance of the stridor within a week. The effect
      lasted 18 months. 

PMID- 24101832
TI  - Chronic meningitis with multiple cranial neuropathies: A rare initial
      presentation of Wegener's granulomatosis.
AB  - Wegener's granulomatosis (WG) is a systemic necrotizing vasculitis that affects
      the small blood vessels. It mainly affects the upper and lower respiratory tract
      and kidneys. Central nervous system (CNS) involvement is rare, and has been
      reported only in about 8% of cases during the course of illness. Initial
      presentation with neurologic affection, particularly chronic hypertrophic
      meningitis is very unusual. We report the case of a 34 year old male who
      presented with chronic hypertrophic meningitis and multiple cranial nerve
      involvement as the initial manifestation, without respiratory and renal symptoms.
      This case highlights the difficulties in diagnosing a rare disease with rarer
      presentation, and at the same time illustrates that Wegener's granulomatosis
      should be considered in the differential diagnosis of chronic meningitis. 

PMID- 24101834
TI  - Methotrexate induced leucoencephalopathy: A stroke mimic.
AB  - With increasing usage of thrombolysis in the treatment of acute ischemic strokes
      within 4.5- hour window, it is becoming more important to recognize stroke
      mimics. Though the incidence of stroke mimics being thrombolysed is less than 3%,
      it is essential to diagnose them so as to avoid wrong thrombolytic treatment
      which carries potential complications of bleeding. We describe the case of a 17
      year old girl with acute lymphoblastic leukemia, who developed stroke like
      episodes on two consecutive challenges with a chemotherapeutic regime which
      included intravenous and intrathecal methotrexate. She had MRI changes consistent
      with acute ischemic stroke on both occasions. Her deficits recovered completely
      and spontaneously, as did the MRI changes. She did not have any further episodes
      when methotrexate was excluded from the chemotherapeutic regime. 

PMID- 24101833
TI  - Perineural spread of rhino-orbitocerebral mucormycosis caused by Apophysomyces
      elegans.
AB  - Rhino-orbitocerebral mucormycosis (ROCM) is a fungal infection commonly affecting
      individuals with diabetes and those in immunocompromised states. However,
      infections caused by Apophysomyces elegans can involve immunocompetent
      individuals. The invasion pattern of cerebral mucormycosis is somewhat
      predictable and may occur by direct invasion or hematogenous spread. Perineural
      spread of the disease is unusual. Here, we report the first case of perineural
      extension of ROCM caused by A. elegans along the trigeminal nerve in a 25-year
      old immunocompetent, nondiabetic individual. 

PMID- 24101835
TI  - Spontaneous evolution of an unusual cortical malformation in SOX2 anophthalmia
      syndrome.
AB  - Brain malformations such as agenesis and dysgenesis of corpus callosum, pituitary
      hypoplasia, hypothalamic hamartoma, mesial temporal periventricular heterotopia,
      and abnormally oriented and misshapen hippocampi have been described with SOX2
      gene mutations. A neocortical malformation is presented here in association with
      SOX2 deletion that over time underwent spontaneous evolution and decrease in
      size. 

PMID- 24101836
TI  - A Turkish family with Sjogren-Larsson syndrome caused by a novel ALDH3A2
      mutation.
AB  - Sjogren-Larsson syndrome (SLS) is an inherited neurocutaneous disorder caused by
      mutations in the aldehyde dehydrogenase family 3 member A2 (ALDH3A2) gene that
      encodes fatty aldehyde dehydrogenase. Affected patients display ichthyosis,
      mental retardation, and spastic diplegia. More than 70 mutations in ALDH3A2 have
      been discovered in SLS patients. We diagnosed two brothers age of 12 and 20 years
      with characteristic features of this rare syndrome. Magnetic resonance imaging
      showed demyelinating disease in both of them. We described a novel homozygous, c.
      835 T > A (p.Y279N) mutation in exon 6 in two patients. 

PMID- 24101837
TI  - A case of crossed aphasia with apraxia of speech.
AB  - Apraxia of speech (AOS) is a rare, but well-defined motor speech disorder. It is
      characterized by irregular articulatory errors, attempts of self-correction and
      persistent prosodic abnormalities. Similar to aphasia, AOS is also localized to
      the dominant cerebral hemisphere. We report a case of Crossed Aphasia with AOS in
      a 48-year-old right-handed man due to an ischemic infarct in right cerebral
      hemisphere. 

PMID- 24101838
TI  - Congestive myelopathy (Foix-Alajouanine Syndrome) due to intradural arteriovenous
      fistula of the filum terminale fed by anterior spinal artery: Case report and
      review of literature.
AB  - Spinal arteriovenous fistulas are rare entities. They often present with
      congestive myelopathy but are infrequently diagnosed as the cause of the
      patients' symptoms. Only one such case has been described previously in Indian
      literature. We describe one such case who presented to us after a gap of 3 years
      since symptom onset and following a failed laminectomy where the cause was later
      diagnosed to be an intradural fistula in the filum terminale fed by the anterior
      spinal artery and review the available literature. 

PMID- 24101839
TI  - Neoplastic Parkinsonism: An illustrative case report.
AB  - Non-Hodgkin's lymphoma of T-cell types are rare neoplasms. Central nervous system
      metastasis is unusual. We are reporting a patient with peripheral T-cell lymphoma
      unspecified who had extra nodal metastasis into the brain that manifested with
      extrapyramidal dysfunction. The clinical presentation was exceptional in that the
      course was indolent and patient had no overt extra neural manifestations of
      malignancy for nearly 3 years after the onset of Parkinsonism. Striking brain
      imaging late in the disease supported by pathological findings enabled the
      diagnosis of this rare condition. 

PMID- 24101840
TI  - Spinal coning after lumbar puncture in a patient with undiagnosed giant cervical
      neurofibroma.
AB  - Lumbar puncture in the presence of an intracranial tumor with raised intracranial
      pressure is known to have catastrophic consequences due to herniation of
      intracranial contents through the tentorial hiatus or foramen magnum. There are
      relatively few case reports about the same sequence of events when lumbar
      puncture is performed below the level of a complete spinal block. The mechanism
      of such deterioration is also subject to conjecture as the spinal cord (unlike
      the uncus or cerebellar tonsils) is tethered by the dentate ligament and roots on
      either side, and is hence less mobile. We present one such case of spinal coning
      and review the available literature. 

PMID- 24101841
TI  - Spectroscopic correlation and role of Azathioprine in long-term remission in
      patients of Hashimoto encephalopathy.
AB  - Hashimoto encephalopathy remains a Rubik's cube for the present generation of
      clinical research. Myriad presentations have been noted, and observations
      recorded in few subgroups of patients have gone on only to be trashed by a second
      group of patients with a completely different clinical profile. Steroids have
      been traditionally held to be the treatment for this condition, but long-term
      side effects associated with it limits its use. Although multiple drugs have been
      tried, yet there exists no data for their long-term efficacy in maintaining
      remission. No radiological findings have been consistently associated with this
      condition. We report the use of azathioprine in maintaining long-term remission
      in one such patient with Hashimoto encephalopathy and the presence of lactate
      peak in magnetic resonance spectroscopy of the patient, which showed dramatic
      regression with institution of immunosuppression. 

PMID- 24101842
TI  - A resident's (unique) position on non-epileptic seizures.

PMID- 24101843
TI  - A comment on idiopathic generalized epilepsy: Phenotypic and
      electroencephalographic observations in a large cohort from South India.

PMID- 24101844
TI  - Reversible dementia as presenting manifestation of racemose neurocysticercosis.

PMID- 24101845
TI  - Opinions about the use of the recognition of stroke in the emergency room scale.

PMID- 24101846
TI  - Cerebrovascular ultrasonography: Quality control.

PMID- 24101847
TI  - A comment on sleep assessment of children with cerebral palsy: Using validated
      sleep questionnaire.

PMID- 24101848
TI  - Comment on "Pathophysiology of migraine" by professor PJ Goadsby in August 2012
      edition of Ann Indian Acad Neurol.

PMID- 24101849
TI  - Author's reply on Pathophysiology of migraine.

PMID- 24101850
TI  - Plexitis or radiculitis secondary to bee sting.

PMID- 24101851
TI  - "Sleep in Wilson's disease: Questionnaire based study" - Comments on the article.

PMID- 24101852
TI  - Authors' reply.

PMID- 24101853
TI  - Improved sensitivity of Kernig's and Brudzinski's sign in diagnosing meningitis
      in children.

PMID- 24101854
TI  - Migraine and restless leg syndrome co-morbidity may be due to iron deficiency.

PMID- 24101855
TI  - Serum iron may not be linked with migraine.

PMID- 24101856
TI  - Efficacy of yoga in treatment of migraine.

PMID- 24101857
TI  - Symptomatic trigeminal neuralgia as the first presentation of acute lymphoblastic
      leukemia.

PMID- 24101859
TI  - Pharmaceutical suspension containing both immediate/sustained-release amoxicillin
      loaded gelatin nanoparticles: preparation and in vitro characterization.
AB  - Pharmaceutical suspension containing oral dosage forms delivering both immediate
      release and sustained-release amoxicillin was developed as a new dosage form to
      eradicate Helicobacter pylori. Amoxicillin-loaded gelatin nanoparticles are able
      to bind with the mucosal membrane after delivery to the stomach and could
      escalate the effectiveness of a drug, providing dual release. The objective of
      this study was to develop amoxicillin nanoparticles using innovative new
      technology--the Buchi Nano Spray Dryer B-90 - and investigate such features as
      drug content, particle morphology, yield, in vitro release, flow properties, and
      stability. The nanoparticles had an average particle size of 571 nm. The drug
      content and percentage yield was 89.2% +/- 0.5% and 93.3% +/- 0.6%, respectively.
      Angle of repose of nanoparticle suspension was 26.3 degrees  and bulk density was
      0.59 g/cm(3). In vitro drug release of formulations was best fitted by first
      order and Peppas models with R (2) of 0.9841 and 0.9837 respectively; release
      profile was 15.9%, while; for the original drug, amoxicillin, under the same
      conditions, 90% was released in the first 30 minutes. The nanoparticles used in
      this study enabled sustained release of amoxicillin over an extended period of
      time, up to 12 hours, and were stable for 12 months under accelerated storage
      conditions of 25  degrees C +/- 2  degrees C and 60% +/- 5% relative humidity.

PMID- 24101860
TI  - Corticosteroid transdermal delivery to target swelling, edema and inflammation
      following facial rejuvenation procedures.
AB  - BACKGROUND AND AIM: The use of transdermal therapeutic systems has spread
      worldwide since they allow effective local drug delivery. In the present study,
      we investigated the efficacy and safety of a new betamethasone valerate medicated
      plaster (Betesil(r)) to manage facial swelling, edema, inflammation, ecchymosis,
      and hematoma, when applied immediately after a facial rejuvenation procedure.
      MATERIALS AND METHODS: We applied the plaster to the skin of 20 healthy patients
      for 12 hours immediately after hyaluronic acid-based procedure performed with the
      aim of erasing facial wrinkles of perioral and nasolabial folds and improving
      chin and eye contour. A further 20 patients underwent the same cosmetic
      procedure, but they were treated with an aescin 10% cream (applied immediately
      after the procedure, in the evening, and the morning after) and served as control
      group. RESULTS: Betesil(r) application resulted in a significant improvement in
      swelling/edema/inflammation score, if compared with aescin 10% cream (P < 0.01).
      As for facial ecchymosis and hematoma around the needle injection track, only two
      patients in the active treatment group displayed minimal ecchymosis and hematoma.
      In the control group, two patients presented minimal ecchymosis and three slight
      hematoma. However, using the ecchymosis/hematoma score, no significant difference
      between Betesil(r) and aescin 10% cream groups was observed. Patients'
      satisfaction was significantly higher among subjects receiving Betesil(r), if
      compared to patients receiving aescin 10% cream (P < 0.01). CONCLUSION: The
      present study supports the use of Betesil(r) plaster immediately after facial
      cosmetic procedures in order to safely control swelling, edema, and inflammation.

PMID- 24101861
TI  - Efficacy, tolerability, and acceptability of bupropion for major depressive
      disorder: a meta-analysis of randomized-controlled trials comparison with
      venlafaxine.
AB  - BACKGROUND: Bupropion and venlafaxine are effective antidepressants with unique
      pharmacological profiles. OBJECTIVES: The purpose of this meta-analysis was to
      determine the efficacy, acceptability, and tolerability of bupropion and
      venlafaxine therapies for adults with major depressive disorder (MDD). The
      authors searched clinical trials with low risk of bias, performed from January
      1985 to February 2013. DATA SOURCES: The searches of MEDLINE, EMBASE, CINAHL,
      PsycINFO, and Cochrane Controlled Trials Register were conducted in February
      2013. Included populations consisted of adult patients with MDD or major
      depression. Study eligible criteria participants and interventions: included
      studies were randomized controlled trials (rcts) comparing bupropion and
      venlafaxine in adult patients with MDD AND OFFERING ENDPOINT RESULTS RELEVANT TO:
      (1) severity of depression; (2) response rate; (3) remission rate; (4) overall
      discontinuation rate; or (5) discontinuation rate due to adverse events.
      Limitation of language was not utilized. STUDY APPRAISAL AND SYNTHESIS METHODS:
      The abstracts located from the electronic databases were reviewed. The completed
      reports from pertinent studies were examined, and essential data were extracted.
      Based on the Cochrane's bias assessment, risks of bias were assessed. Any study
      with two risks or more was excluded. Efficacious outcomes included the mean
      changed scores of rating scales for depression, overall response rates, and
      overall remission rates. Acceptability was determined by the overall
      discontinuation rates. The discontinuation rates due to adverse events were the
      measurement of tolerability. Relative risks (RR) and weighted mean differences or
      standardized mean differences with 95% confidence intervals (CI) were computed
      using a random effect model. RESULTS: A total of 1,117 participants in three RCTs
      were included. Depression rating scales used in one and two studies were the 17
      item Hamilton Depression Rating Scale and the Montgomery-Asberg Depression Rating
      Scale, respectively. The pooled mean changed scores of the bupropion-treated
      group were comparable to those of the venlafaxine-treated group with standardized
      mean differences (95% CI) of 0.05 (-0.16 to 0.26). The overall response and
      remission rates were similar with the RRs (95% CI) of 0.92 (0.79-1.08) and 0.97
      (0.75-1.24), respectively. The pooled overall discontinuation rate and
      discontinuation rate due to adverse events were not different between groups with
      the RRs (95% CI) of 1.00 (0.80-1.26) and 0.69 (0.44-1.10), respectively.
      LIMITATIONS: The small number of RCTs included in the meta-analysis. CONCLUSION:
      According to the limited data obtained from three RCTs, bupropion XL is as
      effective and tolerable as venlafaxine XR for adult patients with MDD. Further
      studies in this area should be conducted to confirm these findings.

PMID- 24101862
TI  - Amniotic fluid stem cells morph into a cardiovascular lineage: analysis of a
      chemically induced cardiac and vascular commitment.
AB  - Mouse embryonic stem cells were previously observed along with mesenchymal stem
      cells from different sources, after being treated with a mixed ester of
      hyaluronan with butyric and retinoic acids, to show a significant increase in the
      yield of cardiogenic and vascular differentiated elements. The aim of the present
      study was to determine if stem cells derived from primitive fetal cells present
      in human amniotic fluid (hAFSCs) and cultured in the presence of a mixture of
      hyaluronic (HA), butyric (BU), and retinoic (RA) acids show a higher yield of
      differentiation toward the cardiovascular phenotype as compared with untreated
      cells. During the differentiation process elicited by exposure to HA + BU + RA,
      genes controlling pluripotency and plasticity of stem cells, such as Sox2, Nanog,
      and Oct4, were significantly downregulated at the transcriptional level. At this
      point, a significant increase in expression of genes controlling the appearance
      of cardiogenic and vascular lineages in HA + BU + RA-treated cells was observed.
      The protein expression levels typical of cardiac and vascular phenotypes,
      evaluated by Western blotting, immunofluorescence, and flow cytometry, were
      higher in hAFSCs cultured in the presence of HA + BU + RA, as compared with
      untreated control cells. Appearance of the cardiac phenotype was further inferred
      by ultrastructural analysis using transmission and scanning electron microscopy.
      These results demonstrate that a mixture of HA + BU + RA significantly increased
      the yield of elements committed toward cardiac and vascular phenotypes,
      confirming what we have previously observed in other cellular types. 

PMID- 24101864
TI  - Predictors of nonadherence with blood pressure regimens in hemodialysis.
AB  - BACKGROUND: Hypertension is very poorly controlled in patients on hemodialysis
      (HD). Demographic and psychosocial predictors of nonadherence with blood pressure
      (BP) regimens in HD have not been investigated. A study of 118 HD patients from
      six outpatient HD units was conducted to determine the relationship between
      demographic/psychosocial factors and adherence with BP-related regimens, ie,
      fluid restriction, BP medication adherence, and HD treatment adherence. METHODS:
      Descriptive statistics, Pearson correlations, and multiple regressions were
      conducted to analyze and determine the relationships between variables. RESULTS:
      Younger age was related to increased fluid gains (r = -0.37, P < 0.01), decreased
      medication adherence (r = -0.19, P = 0.04), increased missed HD treatments (r = 
      0.37, P < 0.01), and diastolic BP (r = -0.60, P < 0.01). Female sex was
      significantly related to decreased fluid gains (r = -0.28, P < 0.01). Race was
      related to increased missed HD treatments (r = 0.22, P = 0.02). Increased social
      support was related to decreased missed HD treatments (r = -0.22, P = 0.02).
      Depression scores were inversely related to decreased medication adherence scores
      (r = 0.24, P = 0.01). CONCLUSION: By identifying risk factors for nonadherence
      with BP-related regimens (young age, male sex, decreased social support, and
      depression), health care providers can plan early clinical intervention to
      minimize the risk of nonadherence.

PMID- 24101863
TI  - Long-term safety and efficacy of etanercept in the treatment of ankylosing
      spondylitis.
AB  - To date, anti-tumor necrosis factor alfa (anti-TNF-alpha) therapy is the only
      alternative to nonsteroidal anti-inflammatory drugs for the treatment of
      ankylosing spondylitis. Etanercept is a soluble TNF receptor, with a mode of
      action and pharmacokinetics different to those of antibodies and distinctive
      efficacy and safety. Etanercept has demonstrated efficacy in the treatment of
      ankylosing spondylitis, with or without radiographic sacroiliitis, and other
      manifestations of the disease, including peripheral arthritis, enthesitis, and
      psoriasis. Etanercept is not efficacious in inflammatory bowel disease, and its
      efficacy in the treatment of uveitis appears to be lower than that of other anti
      TNF drugs. Studies of etanercept confirmed regression of bone edema on magnetic
      resonance imaging of the spine and sacroiliac joint, but failed to reduce
      radiographic progression, as do the other anti-TNF drugs. It seems that a
      proportion of patients remain in disease remission when the etanercept dose is
      reduced or administration intervals are extended. Etanercept is generally well
      tolerated with an acceptable safety profile in the treatment of ankylosing
      spondylitis. The most common adverse effect of etanercept treatment is injection
      site reactions, which are generally self-limiting. Reactivation of tuberculosis,
      reactivation of hepatitis B virus infection, congestive heart failure,
      demyelinating neurologic disorders, hematologic disorders like aplastic anemia
      and pancytopenia, vasculitis, immunogenicity, and exacerbation or induction of
      psoriasis are class effects of all the anti-TNF drugs, and have been seen in
      patients with ankylosing spondylitis. However, etanercept is less likely to
      induce reactivation of tuberculosis than the other anti-TNF drugs and it has been
      suggested that etanercept might be less immunogenic, especially in ankylosing
      spondylitis. Acute uveitis, Crohn's disease, and sarcoidosis are other adverse
      events that have been rarely associated with etanercept therapy in patients with
      ankylosing spondylitis. 

PMID- 24101865
TI  - Antibody and immune memory persistence post infant hepatitis B vaccination.
AB  - OBJECTIVES: This study aimed to evaluate the level of hepatitis B immunity among
      undergraduate students 23 years after commencement of the nationwide hepatitis B
      childhood immunization program in Malaysia. METHODS: A total of 402 serum samples
      obtained from volunteer undergraduate students were screened for the presence of
      hepatitis B surface antibodies using qualitative ELISA. RESULTS: Results showed
      that 62.7% of volunteers had protective anti-hepatitis B surface antigens (>=10
      IU/L), of whom 67.9% received three doses of the vaccine. The estimated post
      vaccination immunity was found to be at least 20 years, indicating persistent
      immunity against hepatitis B and a significant association (P < 0.05) with
      duration of vaccination. Anamnestic response 1 month post-hepatitis B booster was
      94.0% and highly significant (P < 0.01). Isolated antihepatitis B core antigen
      (anti-HBc) prevalence was found to be 5.0%, all having had a positive anamnestic
      response. CONCLUSION: Immunity after primary vaccination with hepatitis B
      recombinant vaccine persists for at least 20 years post-vaccination, with
      significant association with the number of vaccinations. Furthermore, the
      presence of anamnestic response to booster vaccine indicates long-lasting
      immunity despite decreasing antibody levels; therefore, the need for hepatitis B
      vaccine boosters may not be of significant benefit after complete infant
      vaccination.

PMID- 24101866
TI  - Improving engagement in mental health treatment for home meal recipients with
      depression.
AB  - BACKGROUND: Staff who provide support services to older adults are in a unique
      position to detect depression and offer a referral for mental health treatment.
      Yet integrating mental health screening and recommendations into aging services
      requires staff learn new skills to integrate mental health and overcome client
      barriers to accepting mental health referrals. This paper describes client rates
      of depression and a novel engagement intervention (Open Door) for homebound older
      adults who are eligible for home delivered meals and screened for depression by
      in-home aging service programs. METHODS: Homebound older adults receiving meal
      service who endorsed depressive symptoms were interviewed to assess depression
      severity and rates of suicidal ideation. Open Door is a brief psychosocial
      intervention to improve engagement in mental health treatment by collaboratively
      addressing the individual level barriers to care. The intervention targets
      stigma, misconceptions about depression, and fears about treatment, and is
      designed to fit within the roles and responsibilities of aging service staff.
      RESULTS: Among 137 meal recipients who had symptoms when screened for depression
      as part of routine home meal service assessments, half (51%) had Major Depressive
      Disorder and 13% met criteria for minor depression on the SCID. Suicidal ideation
      was reported by 29% of the sample, with the highest rates of suicidal ideation
      (47%) among the subgroup of individuals with Major Depressive Disorder.
      CONCLUSION: Individuals who endorse depressive symptoms during screening are
      likely to have clinically significant depression and need mental health
      treatment. The Open Door intervention offers a strategy to overcome barriers to
      mental health treatment engagement and to improve the odds of quality care for
      depression.

PMID- 24101867
TI  - Eldecalcitol for the treatment of osteoporosis.
AB  - Eldecalcitol (1alpha, 25-dihydroxy-2beta-[3-hydroxypropyloxy] vitamin D3; ED-71)
      is a new analog of the active form of vitamin D. Eldecalcitol has recently been
      approved for the treatment of osteoporosis in Japan. In addition to regulation of
      calcium metabolism carried out by conventional vitamin D analogs, eldecalcitol
      possesses a strong inhibitory effect on bone resorption and causes a significant
      increase in bone mineral density. A Phase III clinical trial on osteoporosis
      showed that eldecalcitol reduced the incidence of new vertebral fractures over 3
      years by 26% compared with alfacalcidol. Although the overall risk of
      nonvertebral fractures was not reduced by eldecalcitol, the risk of wrist
      fracture was decreased significantly in the eldecalcitol group (71%) compared
      with the alfacalcidol group. The serum level of 25-hydroxyvitamin D (25[OH]D) was
      normalized by supplementation of native vitamin D in this trial, so the desirable
      effects on bone by eldecalcitol were considered to be derived from its
      distinctive pharmacological action. Increased blood calcium was observed in 21%
      of patients treated with eldecalcitol, and hypercalcemia (>11.5 mg/dL) occurred
      in 0.4% of eldecalcitol recipients, so serum calcium concentration should be
      monitored after starting eldecalcitol treatment. Eldecalcitol has dual effects on
      the metabolism of bone and calcium and is useful for the treatment of
      osteoporosis, especially for elderly patients (who frequently suffer from vitamin
      D deficiency). This article reviews the clinical efficacy and safety of
      eldecalcitol in the treatment of osteoporosis. 

PMID- 24101868
TI  - Conjugation of glucosamine with Gd3+-based nanoporous silica using a
      heterobifunctional ANB-NOS crosslinker for imaging of cancer cells.
AB  - BACKGROUND: The aim of this study was to synthesize Gd(3+)-based silica
      nanoparticles that conjugate easily with glucosamine and to investigate their use
      as a nanoprobe for detection of human fibrosarcoma cells. METHODS: Based on the
      structure of the 2-fluoro-2-deoxy-D-glucose molecule ((18)FDG), a new compound
      consisting of D-glucose (1.1 nm) was conjugated with a Gd(3+)-based mesoporous
      silica nanoparticle using an N-5-azido-2-nitrobenzoyloxy succinimide (ANB-NOS)
      crosslinker The contrast agent obtained was characterized using a variety of
      methods, including Fourier transform infrared spectroscopy, nitrogen
      physisorption, thermogravimetric analysis, scanning and transmission electron
      microscopy, and inductively coupled plasma atomic emission spectrometry (ICP
      AES). In vitro studies included cell toxicity, apoptosis, tumor necrosis factor
      alpha, and hexokinase assays, and in vivo tests consisted of evaluation of blood
      glucose levels using the contrast compound and tumor imaging. The cellular uptake
      study was validated using ICP-AES. Magnetic resonance relaxivity of the contrast
      agent was determined using a 1.5 Tesla scanner. RESULTS: ANB-NOS was found to be
      the preferred linker for attaching glucosamine onto the surface of the mesoporous
      silica nanospheres. The r1 relaxivity for the nanoparticles was 17.70 mM(-1)s(-1)
      per Gd(3+) ion, which is 4.4 times larger than that for Magnevist(r) (r1
      approximately 4 mM(-1)s(-1) per Gd(3+) ion). The compound showed suitable
      cellular uptake (75.6% +/- 2.01%) without any appreciable cytotoxicity.
      CONCLUSION: Our results suggest that covalently attaching glucosamine molecules
      to mesoporous silica nanoparticles enables effective targeted delivery of a
      contrast agent.

PMID- 24101869
TI  - Codelivery of curcumin and doxorubicin by MPEG-PCL results in improved efficacy
      of systemically administered chemotherapy in mice with lung cancer.
AB  - Systemic administration of chemotherapy for cancer often has toxic side effects,
      limiting the doses that can be used in its treatment. In this study, we developed
      methoxy poly(ethylene glycol)-poly(caprolactone) (MPEG-PCL) micelles loaded with
      curcumin and doxorubicin (Cur-Dox/MPEG-PCL) that were tolerated by recipient mice
      and had enhanced antitumor effects and fewer side effects. It was shown that
      these Cur-Dox/MPEG-PCL micelles could release curcumin and doxorubicin slowly in
      vitro. The long circulation time of MPEG-PCL micelles and the slow rate of
      release of curcumin and doxorubicin in vivo may help to maintain plasma
      concentrations of active drug. We also demonstrated that Cur-Dox/MPEG-PCL had
      improved antitumor effects both in vivo and in vitro. The mechanism by which Cur
      Dox/MPEG-PCL micelles inhibit lung cancer might involve increased apoptosis of
      tumor cells and inhibition of tumor angiogenesis. We found advantages using Cur
      Dox/MPEG-PCL micelles in the treatment of cancer, with Cur-Dox/MPEG-PCL achieving
      better inhibition of LL/2 lung cancer growth in vivo and in vitro. Our study
      indicates that Cur-Dox/MPEG-PCL micelles may be an effective treatment strategy
      for cancer in the future. 

PMID- 24101870
TI  - Vitamin C-driven epirubicin loading into liposomes.
AB  - The encapsulation of anticancer drugs in a liposome structure protects the drug
      during circulation and increases drug accumulation in the cancer tissue and
      antitumor activity while decreasing drug toxicity. This paper presents a new
      method of active drug loading based on a vitamin C pH/ion gradient. Formulations
      were characterized in terms of the following parameters: optimal external pH,
      time and drug-to-lipid ratio for the purpose of remote loading, and in vitro
      stability. In the case of the selected drug, epirubicin (EPI), its
      coencapsulation increases its anticancer activity through a possibly synergistic
      effect previously reported by other groups for a free nonencapsulated
      drug/vitamin C cocktail. The method also has another advantage over other remote
      loading methods: it allows faster drug release through liposome destabilization
      at the tumor site, thanks to the very good solubility of the EPI vitamin C salt,
      as seen on cryogenic transmission electron microscopy images. This influences the
      drug-release process and increases the anticancer activity of the liposome
      formulation. The liposomes are characterized as stable, with very good
      pharmacokinetics (half-life 18.6 hours). The antitumor activity toward MCF-7 and
      4T-1 breast cancer cells was higher in the case of EPI loaded via our gradient
      than via an ammonium sulfate gradient. Finally, the EPI liposomal formulation and
      the free drug were tested using the murine 4T-1 breast cancer model. The
      antitumor activity of the encapsulated drug was confirmed (tumor-growth
      inhibition over 40% from day 16 until the end of the experiment), and the free
      drug was shown to have no anticancer activity at the tested dose. 

PMID- 24101871
TI  - Effects of titanium nanoparticles on adhesion, migration, proliferation, and
      differentiation of mesenchymal stem cells.
AB  - BACKGROUND: The purpose of this study was to investigate the influences of
      nanoscale wear particles derived from titanium/titanium alloy-based implants on
      integration of bone. Here we report the potential impact of titanium oxide (TiO2)
      nanoparticles on adhesion, migration, proliferation, and differentiation of
      mesenchymal stem cells (MSC) from the cellular level to the molecular level in
      the Wistar rat. METHODS: A series of TiO2 nanoparticles (14 nm, 108 nm, and 196
      nm) were synthesized and characterized by scanning electron microscopy and
      transmission electron microscopy, respectively. RESULTS: The TiO2 nanoparticles
      had negative effects on cell viability, proliferation, and the cell cycle of MSC
      in a dose-dependent and size-dependent manner. Confocal laser scanning microscopy
      was used to investigate the effects of particle internalization on adhesion,
      spreading, and morphology of MSC. The integrity of the cell membrane,
      cytoskeleton, and vinculin of MSC were negatively influenced by large TiO2
      nanoparticles. CONCLUSION: The Transwell migration assay and a wound healing
      model suggested that TiO2 nanoparticles had a strong adverse impact on cell
      migration as particle size increased (P < 0.01). Furthermore, alkaline
      phosphatase, gene expression of osteocalcin (OC) and osteopontin (OPN), and
      mineralization measurements indicate that the size of the TiO2 nanoparticles
      negatively affected osteogenic differentiation of MSC.

PMID- 24101872
TI  - A peptide-mediated targeting gene delivery system for malignant glioma cells.
AB  - Glioblastoma multiforme (GBM) is the most common and malignant glioma. Although
      there has been considerable progress in treatment strategies, the prognosis of
      many patients with GBM remains poor. In this work, polyethylenimine (PEI) and the
      VTWTPQAWFQWV (VTW) peptide were modified and synthesized into GBM-targeting
      nanoparticles. The transfection efficiency of U-87 (human glioblastoma) cells was
      evaluated using fluorescence microscopy and flow cytometry. Cell internalization
      was investigated to verify the nanoparticle delivery into the cytoplasm. Results
      showed that the methods of polymer conjugation and the amount of VTW peptide were
      important factors to polymer synthesis and transfection. The PEI-VTW20
      nanoparticles increased the transfection efficiency significantly. This report
      describes the use of VTW peptide-based PEI nanoparticles for intracellular gene
      delivery in a GBM cell-specific manner. 

PMID- 24101873
TI  - Nanoinformatics for biomedicine: emerging approaches and applications.
AB  - This special issue on nanoinformatics for biomedicine is a collection of recent
      papers from the 2012 IEEE Workshop on Nanoinformatics for Biomedicine (NanoInfo
      2012) and other work in the area. These papers illustrate different aspects of
      nanoinformatics to support biomedical research and to advance knowledge on
      nanomaterial-biological interactions. The topics covered include data curation,
      data standards, data mining and predictive modeling, machine learning, and
      translational research. The objectives of this special issue are multifold: (1)
      to bring together and showcase some of the latest research results in the field;
      (2) to introduce some useful repositories, systems, and analysis tools; and (3)
      to stimulate more research activities in the field. 

PMID- 24101874
TI  - Effect of the sun on visible clinical signs of aging in Caucasian skin.
AB  - OBJECTIVES: AGING SIGNS CAN BE CLASSIFIED INTO FOUR MAIN CATEGORIES:
      wrinkles/texture, lack of firmness of cutaneous tissues (ptosis), vascular
      disorders, and pigmentation heterogeneities. During a lifetime, skin will change
      in appearance and structure not only because of chronological and intrinsic
      processes but also due to several external factors such as gravity, sun and
      ultraviolet exposure, and high levels of pollution; or lifestyle factors that
      have important and obvious effects on skin aging, such as diet, tobacco, illness,
      or stress. The effect of these external factors leads to progressive degradations
      of tegument that appear with different kinetics. The aim of this study was to
      clinically quantify the effect of sun exposure on facial aging in terms of the
      appearance of new specific signs or in terms of increasing the classical signs of
      aging. MATERIALS AND METHODS: This study was carried out on 298 Caucasian women
      from 30 years to 78 years old. The participants were divided into two groups
      according to their sun exposure history: 157 women were characterized as sun
      seeking, and the other 141 were classified as sun-phobic. This division was made
      possible by dermatologist grading of heliodermal status on the basis of several
      observations of classic criteria: wrinkles, sagging, pigmentation
      heterogeneities, vascular disorders, elastosis, and so on. This work was an
      opportunity to complete clinical photographic tools by adding in our portfolio
      new scales for signs observed in the two groups. Thus, 22 clinical parameters
      were investigated by a panel of twelve trained experts to characterize each
      woman's face regarding standardized photographic scales, and thus describe the
      aging process. RESULTS: By calculating statistical correlations between the four
      clinical clusters (wrinkles/texture, ptosis, vascular disorders, and pigmentation
      disorders), and real age and apparent age on the one hand and heliodermal status
      on the other hand, we identified a link between each clinical cluster and aging
      and the photoaging process. By comparing evaluations of clinical signs between
      the two groups for each 10-year cluster, we demonstrated that whatever the age, a
      prevalence of pigmentation disorders for the sun-seeking group (ie, pigmentation)
      is strongly linked to ultraviolet (UV) exposure. Meanwhile, clinical signs of
      ptosis are linked more to chronological aging and do not present differences
      between the two groups, nor, therefore, photoaging. Wrinkles and texture are
      affected by the two aging processes. Finally, clinical signs of vascular
      disorders present no evolution with age. CONCLUSION: Clinical signs of aging are
      essentially influenced by extrinsic factors, especially sun exposure. Indeed UV
      exposure seems to be responsible for 80% of visible facial aging signs.

PMID- 24101875
TI  - Vascular endothelial growth factor inhibitors: investigational therapies for the
      treatment of psoriasis.
AB  - Psoriasis is a common inflammatory autoimmune condition in which environmental
      factors and genetic predisposition contribute to the development of disease in
      susceptible individuals. Angiogenesis is known to be a key pathogenic feature of
      psoriasis. Local and systemic elevation of vascular endothelial growth factor
      (VEGF)-A has been demonstrated in the skin and plasma of patients with psoriasis
      and is known to correlate with improvement following some traditional psoriasis
      treatments. A number of VEGF inhibitors are licensed for the treatment of
      malignancies and eye disease and isolated case reports suggest that some
      individuals with psoriasis may improve when exposed to these agents. The small
      number of cases and lack of unified reporting measures makes it difficult to draw
      generalizations and underline the heterogeneity of psoriasis as a disease entity.
      Though not yet licensed for the treatment of psoriasis in humans, experimental
      data supports the potential of VEGF inhibitors to influence relevant aspects of
      human cell biology (such as endothelial cell differentiation) and to improve
      animal models of skin disease. Given the multi-factorial nature of psoriasis it
      is unlikely that VEGF inhibitors will be effective in all patients, however they
      have the potential to be a valuable addition to the therapeutic arsenal in
      selected cases. Current VEGF inhibitors in clinical use are associated with a
      number of potentially serious side effects including hypertension, left
      ventricular dysfunction, and gastrointestinal perforation. Such risks require
      careful consideration in psoriasis populations particularly in light of growing
      concerns linking psoriasis to increased cardiovascular risk. 

PMID- 24101876
TI  - Lack of correlation between in silico projection of function and quantitative
      real-time PCR-determined gene expression levels in colon tissue.
AB  - There are a number of in silico programs that use algorithms and external web
      sources to predict the effect of single nucleotide polymorphisms (SNPs). While
      many of these programs have been shown to predict accurately the effect of SNPs
      in functional areas of the gene, such as 5' upstream or coding regions, empiric
      research may be warranted to confirm the functional consequences of SNPs that are
      predicted to have little to no effect. We compared predictions from FASTSNP
      (Function Analysis and Selection Tool for Single Nucleotide Polymorphism) and F
      SNP (Functional Single Nucleotide Polymorphism) with experimentally derived
      genotype-phenotype correlations to determine the accuracy of these programs in
      predicting SNP functionality. We used normal colon tissue to evaluate 24 TagSNPs
      within six genes. Two of 16 SNPs that were predicted to have no functional effect
      in FASTSNP were significantly associated with gene expression. Only one of the
      eight SNPs that were predicted to have a low to high effect was significantly
      associated with gene expression. While the two in silico programs that were used
      were similar in their results for the SNPs predicted by FASTSNP to have no
      effect, of SNPs with scores from low to high, there were three that received an F
      SNP score below what is considered functionally significant. In silico programs
      can fail to identify functional SNPs, supporting a continuing role for empiric
      analysis of SNP function. Laboratory analysis is necessary to identify causal
      SNPs accurately, establish biological plausibility of the effect, and ultimately
      inform cancer prevention strategies. 

PMID- 24101877
TI  - Delivering pharmacogenetic testing in a primary care setting.
AB  - Pharmacogenetic testing refers to a type of genetic test to predict a patient's
      likelihood to experience an adverse event or not respond to a given drug. Despite
      revision to several labels of commonly prescribed drugs regarding the impact of
      genetic variation, the use of this testing has been limited in many settings due
      to a number of factors. In the primary care setting, the limited office time as
      well as the limited knowledge and experience of primary care practitioners have
      likely attributed to the slow uptake of pharmacogenetic testing. This paper
      provides talking points for primary care physicians to discuss with patients when
      pharmacogenetic testing is warranted. As patients and physicians become more
      familiar and accepting of pharmacogenetic testing, it is anticipated that
      discussion time will be comparable to that of other clinical tests. 

PMID- 24101878
TI  - Growth evaluation of a group of children enrolled in public schools in Rabat,
      Morocco: the role of socioeconomic factors.
AB  - OBJECTIVES: The aim of this study was to assess the prevalence of underweight,
      stunting, and the socioeconomic risk factors among children enrolled in primary
      public schools in Rabat, Morocco. METHODS: Twenty-three schools were randomly
      selected. A cross-sectional study was conducted between April and June 2010. The
      survey was conducted on the basis of two questionnaires for both parents and
      children. The references used were from the World Health Organization, 2007.
      RESULTS: Our study focused on a sample of 1569 children whose average age was 9.7
      +/- 0.95 years. The prevalence of underweight among girls and boys was 43.1%,
      while that of stunting was 18.2%. The majority of the children in our population
      come from a low socioeconomic level. While 59% of fathers are laborers, 85% of
      mothers are unemployed. CONCLUSION: In our study, we demonstrated that child
      malnutrition is strongly linked to a low socioeconomic level. These observations
      suggest that besides income, schooling and food quality may also be important
      factors that can affect growth. Educational programs, whether held in schools or
      informally, such as literacy or parenting classes, are valuable complements to
      other nutrition sustaining activities.

PMID- 24101879
TI  - Hydrogen potassium adenosine triphosphatase activity inhibition and
      downregulation of its expression by bioactive fraction DLBS2411 from Cinnamomum
      burmannii in gastric parietal cells.
AB  - This study assessed the gastric acid antisecretory effect of DLBS2411
      fractionated from Cinnamomum burmannii. Hydrogen potassium adenosine
      triphosphatase (H(+)/K(+) ATPase) activity and its gene expression were observed,
      and the antioxidant activity of DLBS2411 was also investigated. Treatment of
      DLBS2411 decreased the level of H(+)/K(+) ATPase messenger RNA expression on
      human embryonic kidney 293 cells and rat gastric parietal cells in a dose
      dependent manner, in vitro and ex vivo. DLBS2411 also acted as a competitive
      inhibitor by showing inhibition in gastric H(+)/K(+) ATPase activity at various
      pHs. In gastric ulcer animal models induced with indomethacin and ethanol,
      DLBS2411showed a reduction in the number of petechiae, suggesting that the
      fraction also confers gastroprotective activity. Moreover, DLBS2411 was also
      found to have potent antioxidant activity. Taken together, DLBS2411 is a
      promising novel agent for the management of dyspepsia, a condition of
      hyperacidity and diseases in the stomach requiring gastroprotection. 

PMID- 24101880
TI  - Analgesia for pain during subcutaneous injection: effectiveness of manual
      pressure application before injection.
AB  - BACKGROUND: It is necessary to establish an effective subcutaneous injection
      procedure for adult and elderly individuals because many drugs such as hormones
      and interferon are generally delivered by subcutaneous injection. We tested
      whether pain during subcutaneous injection can be decreased by prior application
      of localized manual pressure at the injection site. METHODS: In this
      semirandomized, open-label study evaluating the manual pressure method for
      transient analgesia, physicians applied pressure with their thumbs for 10 seconds
      to create a nonpainful skin depression at the injection site immediately before
      subcutaneous injection of the influenza vaccine to patients. Control patients
      received the vaccine by the same route, but without prior application of focal
      pressure. In addition to pain, we evaluated patient age, gender, height, weight,
      body mass index, body temperature, and fat thickness at the brachial triceps
      muscle. Pain intensity was estimated using a 100 mm visual analog scale (VAS) and
      the face scale (FS). Categorical variables were compared using Chi-square tests
      and continuous variables were compared using unpaired t-tests between the
      intervention group and control group. Multivariate analysis was performed using
      the VAS or FS score as the dependent variable and weight, age, height, fat
      thickness at the brachial triceps muscle, and body temperature as independent
      variables. RESULTS: There were no significant differences in demographic
      variables, VAS scores (22.5 +/- 23.0 versus 21.2 +/- 23.6, P = 0.4), or FS scores
      (2.5 +/- 2.1 versus 2.4 +/- 2.1, P = 0.4) between the intervention and control
      groups. There was a significant negative correlation between age and subjective
      pain intensity (VAS, r = -0.32; FS, r = -0.28). CONCLUSION: The manual pressure
      method was not effective in decreasing pain during subcutaneous injection.
      Alternative methods of focal transient analgesia should be developed to improve
      vaccination rates and relieve anxiety associated with subcutaneous injection.

PMID- 24101881
TI  - Causal diagrams, the placebo effect, and the expectation effect.
AB  - Using causal diagrams, a formal research methodology, we analyzed several
      definitions of placebo and the placebo effect. We conclude that placebo is an
      ambiguous, redundant term and that the so-called placebo effect conceals far more
      interesting effects that are attributed to the patient's expectation. Biomedical
      research will benefit from abandoning the term placebo effect and focusing
      instead on a deeper understanding of the expectation variable, including its
      causes, effects, and effect modifiers. This avenue of research should be pursued
      by observational cohorts that are nested within clinical trials. 

PMID- 24101882
TI  - Treating resistant hypertension: role of renal denervation.
AB  - Arterial hypertension is the most prevalent risk factor associated with increased
      cardiovascular morbidity and mortality. Although pharmacological treatment is
      generally well tolerated, 5%-20% of patients with hypertension are resistant to
      medical therapy, which is defined as blood pressure above goal (>140/90 mmHg in
      general; >130-139/80-85 mmHg in patients with diabetes mellitus; >130/80 mmHg in
      patients with chronic kidney disease) despite treatment with >=3 antihypertensive
      drugs of different classes, including a diuretic, at optimal doses. These
      patients are at significantly higher risk for cardiovascular events, in
      particular stroke, myocardial infarction, and heart failure, as compared with
      patients with nonresistant hypertension. The etiology of resistant hypertension
      is multifactorial and a number of risk factors have been identified. In addition,
      resistant hypertension might be due to secondary causes such as primary
      aldosteronism, chronic kidney disease, renal artery stenosis, or obstructive
      sleep apnea. To identify patients with resistant hypertension, the following must
      be excluded: pseudo-resistance, which might be due to nonadherence to medical
      treatment; white-coat effect; and inaccurate measurement technique. Activation of
      the sympathetic nervous system contributes to the development and maintenance of
      hypertension by increasing renal renin release, decreasing renal blood flow, and
      enhancing tubular sodium retention. Catheter-based renal denervation (RDN) is a
      novel technique specifically targeting renal sympathetic nerves. Clinical trials
      have demonstrated that RDN significantly reduces blood pressure in patients with
      resistant hypertension. Experimental studies and small clinical studies indicate
      that RDN might also have beneficial effects in other diseases and comorbidities,
      characterized by increased sympathetic activity, such as left ventricular
      hypertrophy, heart failure, metabolic syndrome and hyperinsulinemia, atrial
      fibrillation, obstructive sleep apnea, and chronic kidney disease. Further
      controlled studies are required to investigate the role of RDN beyond blood
      pressure control. 

PMID- 24101884
TI  - Erratum: Mycobacterium avium-intracellulare otomastoiditis in a young AIDS
      patient: case report and review of the literature [Corrigendum].
AB  - [This corrects the article on p. 61 in vol. 5, PMID: 23459156.].

PMID- 24101883
TI  - Safety of protease inhibitors in HIV-infected pregnant women.
AB  - The dire conditions of the human immunodeficiency virus/acquired immune
      deficiency syndrome epidemic and the immense benefits of antiretroviral
      prophylaxis in prevention of mother-to-child transmission far outweigh the
      potential for adverse effects and undeniably justify the rapid and widespread use
      of this therapy, despite incomplete safety data. Highly active antiretroviral
      therapy has now become standard care, and more than half the validated regimens
      include protease inhibitors. This paper reviews current knowledge of the safety
      of these drugs during pregnancy, in terms of maternal and fetal outcomes.
      Transfer of protease inhibitors across the placenta is known to be minimal, and
      current data about birth defects and fetal malignancies are reassuring. Maternal
      liver function and glucose metabolism should be monitored in women treated with
      protease inhibitor-based regimens, but concerns about the development of maternal
      resistance, should treatment be discontinued, have been shown to be groundless.
      Neonates should be screened for hematologic abnormalities, although these are
      rarely severe or permanent and are not usually related to the protease inhibitor
      component of the antiretroviral combination. Current findings concerning pre
      eclampsia and growth restriction are discordant, and further research is needed
      to address the question of placental vascular complications. The increased risk
      of preterm birth attributed to protease inhibitors should be interpreted with
      caution considering the discrepant results and the multitude of confounding
      factors often overlooked. Although data are thus far reassuring, further research
      is needed to shed light on unresolved controversies about the safety of protease
      inhibitors during pregnancy. 

PMID- 24101885
TI  - Quality of life among people living with acquired immune deficiency syndrome
      receiving anti-retroviral therapy: a study from Nepal.
AB  - PURPOSE: The present study was undertaken to determine the impact of acquired
      immune deficiency syndrome (AIDS) on the quality of life of affected individuals
      in Nepal. PATIENTS AND METHODS: A cross sectional study was done among 70
      individuals attending the Anti-Retroviral Therapy clinic of the University
      Hospital in Nepal. Quality of life (QOL) was evaluated using World Health
      Organization Quality of life questionnaire (WHO QOL-BREF) instrument. Statistical
      analysis was done using SPSS Version 17.0. RESULTS: The median scores with
      interquartile range (IQR) in four domains of QOL in descending order were
      physical (61; IQR 22), social (58; IQR 33), environmental (56; IQR 13), and
      psychological (54; IQR 8). Older age was associated with lower perceived overall
      QOL. Females were more likely to have lower QOL scores in the social and
      psychological domains. Higher CD4 counts and a married status were significant
      predictors of higher QOL scores in the environmental domain. CONCLUSION: Being
      older, female, single, and having advanced clinical stage is associated with
      lower QOL scores in people living with AIDS. Lowest QOL scores were seen in the
      psychological domain suggesting the need of psychological interventions.

PMID- 24101886
TI  - National study of continuity clinic satisfaction in pediatric fellowship
      training.
AB  - BACKGROUND: A national online survey was conducted to evaluate pediatric
      subspecialty fellow satisfaction regarding continuity clinic experience. METHODS:
      An anonymous online survey (SurveyMonkeyTM) was developed to evaluate
      demographics of the program, clinic organization, and patient and preceptor
      characteristics, and to compare fellow satisfaction when fellows were the primary
      providers with faculty supervision versus attending-run clinics assisted by
      fellows or a combination of the two models. Pediatric subspecialty fellows in a 3
      year Accreditation Council for Graduate Medical Education accredited program in
      the United States (excluding emergency medicine, neonatology, and critical care)
      were invited to participate. RESULTS: There were 644 respondents and nearly half
      (54%) of these had fellow-run clinics. Eighty-six percent of fellows responded
      that they would prefer to have their own continuity clinics. Higher satisfaction
      ratings on maintaining continuity of care, being perceived as the primary
      provider, and feeling that they had greater autonomy in patient management were
      associated with being part of a fellow-run clinic experience (all P < 0.001).
      Additionally, fellow-run clinics were associated with a feeling of increased
      involvement in designing a treatment plan based on their differential diagnosis
      (P < 0.001). There were no significant associations with patient or preceptor
      characteristics. CONCLUSION: Fellow-run continuity clinics provide fellows with a
      greater sense of satisfaction and independence in management plans.

PMID- 24101887
TI  - The transformation of continuing medical education (CME) in the United States.
AB  - This article describes five major themes that inform and highlight the
      transformation of continuing medical education in the USA. Over the past decade,
      the Institute of Medicine (IOM) and other national entities have voiced concern
      over the cost of health care, prevalence of medical errors, fragmentation of
      care, commercial influence, and competence of health professionals. The
      recommendations from these entities, as well as the work of other regulatory,
      professional, academic, and government organizations, have fostered discussion
      and development of strategies to address these challenges. The five themes in
      this paper reflect the changing expectations of multiple stakeholders engaged in
      health care. Each theme is grounded in educational, politico-economic priorities
      for health care in the USA. The themes include (1) a shift in expectation from
      simple attendance or a time-based metric (credit) to a measurement that infers
      competence in performance for successful continuing professional development
      (CPD); (2) an increased focus on interprofessional education to augment
      profession-specific continuing education; (3) the integration of CPD with quality
      improvement; (4) the expansion of CPD to address population and public health
      issues; and (5) identification and standardization of continuing education (CE)
      professional competencies. The CE profession plays an essential role in the
      transformation of the US CPD system for health professionals. Coordination of the
      five themes described in this paper will foster an improved, effective, and
      efficient health system that truly meets the needs of patients. 

PMID- 24101888
TI  - A pilot study: research poster presentations as an educational tool for
      undergraduate epidemiology students.
AB  - Students in a fourth year epidemiology course were surveyed after participating
      in a formal Science Research Day in which they presented original research, in
      poster form, to be judged by scientists from the community. Of 276 participating
      students, 80 (29%) responded to the study survey. As a result, 19% of respondents
      were more likely to pursue a career in science, and 27.5% were more likely to
      pursue a career in epidemiology. Only one respondent reported being less likely
      to pursue a science career, while seven were less likely to pursue epidemiology.
      A majority of respondents felt that the poster experience was on par with, or
      superior to, a comparable research paper, in terms of both educational appeal and
      enjoyment. Mandatory, formal poster presentations are an innovative format for
      teaching advanced health sciences, and may more accurately reflect the realities
      of a science career than do more traditional educational formats. 

PMID- 24101889
TI  - Medical and surgical ward rounds in teaching hospitals of Kuwait University:
      students' perceptions.
AB  - BACKGROUND: Teaching sessions for medical students during ward rounds are an
      essential component of bedside teaching, providing students with the opportunity
      to regard patients as actual people, and to observe their physical conditions
      directly, allowing a better understanding of illnesses to be developed. We aim to
      explore medical students' perceptions regarding medical and surgical ward rounds
      within the Faculty of Medicine at Kuwait University, and to evaluate whether this
      teaching activity is meeting the expectation of learners. METHODS: A pretested
      questionnaire was used to collect data from 141 medical students during the 2012
      2013 academic year. They were asked to provide their current and expected ratings
      about competencies that were supposed to be gained during ward rounds, on a scale
      from 1 (lowest) to 5 (highest). Mean scores were calculated, and the Student t
      test was used to compare results. P < 0.05 was the cut-off level for
      significance. RESULTS: Only 17 students (12.1%) declined to participate in the
      study. The students' current competency scores (for competencies taught within
      both disciplines - medical and surgical) were significantly lower than the scores
      indicating students' expectations (P < 0.001). The best-taught competency was
      bedside examination, in both medical (mean: 3.45) and surgical (mean: 3.05) ward
      rounds. However, medical ward rounds were better than surgical rounds in covering
      some competencies, especially the teaching of professional attitude and approach
      towards patients (P < 0.001). CONCLUSION: Both medical and surgical ward rounds
      were deficient in meeting the students' expectations. Medical educators should
      utilize the available literature to improve the bedside teaching experience for
      their students.

PMID- 24101890
TI  - Group versus modified individual standard-setting on multiple-choice questions
      with the Angoff method for fourth-year medical students in the internal medicine
      clerkship.
AB  - BACKGROUND: The Angoff method is one of the preferred methods for setting a
      passing level in an exam. Normally, group meetings are required, which may be a
      problem for busy medical educators. Here, we compared a modified Angoff
      individual method to the conventional group method. METHODS: SIX CLINICAL
      INSTRUCTORS WERE DIVIDED INTO TWO GROUPS MATCHED BY TEACHING EXPERIENCE: modified
      Angoff individual method (three persons) and conventional group method (three
      persons). The passing scores were set by using the Angoff theory. The groups set
      the scores individually and then met to determine the passing score. In the
      modified Angoff individual method, passing scores were judged by each instructor
      and the final passing score was adjusted by the concordance method and
      reliability index. RESULTS: There were 94 fourth-year medical students who took
      the test. The mean (standard deviation) test score was 65.35 (8.38), with a
      median of 64 (range 46-82). The three individual instructors took 45, 60, and 60
      minutes to finish the task, while the group spent 90 minutes in discussion. The
      final passing score in the modified Angoff individual method was 52.18 (56.75
      minus 4.57) or 52 versus 51 from the standard group method. There was not much
      difference in numbers of failed students by either method (four versus three).
      CONCLUSION: The modified Angoff individual method may be a feasible way to set a
      standard passing score with less time consumed and more independent rather than
      group work by instructors.

PMID- 24101891
TI  - Artificial dispersion via high-order homogenization: magnetoelectric coupling and
      magnetism from dielectric layers.
AB  - We investigate a high-order homogenization (HOH) algorithm for periodic multi
      layered stacks. The mathematical tool of choice is a transfer matrix method.
      Expressions for effective permeability, permittivity and magnetoelectric coupling
      are explored by frequency power expansions. On the physical side, this HOH
      uncovers a magnetoelectric coupling effect (odd-order approximation) and
      artificial magnetism (even-order approximation) in moderate contrast photonic
      crystals. Comparing the effective parameters' expressions of a stack with three
      layers against that of a stack with two layers, we note that the magnetoelectric
      coupling effect vanishes while the artificial magnetism can still be achieved in
      a centre-symmetric periodic structure. Furthermore, we numerically check the
      effective parameters through the dispersion law and transmission property of a
      stack with two dielectric layers against that of an effective bianisotropic
      medium: they are in good agreement throughout the low-frequency (acoustic) band
      until the first stop band, where the analyticity of the logarithm function of the
      transfer matrix ([Formula: see text]) breaks down.

PMID- 24101892
TI  - The entropy concept for non-equilibrium states.
AB  - In earlier work, we presented a foundation for the second law of classical
      thermodynamics in terms of the entropy principle. More precisely, we provided an
      empirically accessible axiomatic derivation of an entropy function defined on all
      equilibrium states of all systems that has the appropriate additivity and scaling
      properties, and whose increase is a necessary and sufficient condition for an
      adiabatic process between two states to be possible. Here, after a brief review
      of this approach, we address the question of defining entropy for non-equilibrium
      states. Our conclusion is that it is generally not possible to find a unique
      entropy that has all relevant physical properties. We do show, however, that one
      can define two entropy functions, called S- and S+, which, taken together,
      delimit the range of adiabatic processes that can occur between non-equilibrium
      states. The concept of comparability of states with respect to adiabatic changes
      plays an important role in our reasoning.

PMID- 24101893
TI  - Erratum: Notice of redundant publication Strength of electromagnetic, acoustic
      and Schrodinger reflections.
AB  - [This corrects the article DOI: 10.1098/rspa.2008.0100.].

PMID- 24101894
TI  - How do astrocytes shape synaptic transmission? Insights from electrophysiology.
AB  - A major breakthrough in neuroscience has been the realization in the last decades
      that the dogmatic view of astroglial cells as being merely fostering and
      buffering elements of the nervous system is simplistic. A wealth of
      investigations now shows that astrocytes actually participate in the control of
      synaptic transmission in an active manner. This was first hinted by the intimate
      contacts glial processes make with neurons, particularly at the synaptic level,
      and evidenced using electrophysiological and calcium imaging techniques. Calcium
      imaging has provided critical evidence demonstrating that astrocytic regulation
      of synaptic efficacy is not a passive phenomenon. However, given that cellular
      activation is not only represented by calcium signaling, it is also crucial to
      assess concomitant mechanisms. We and others have used electrophysiological
      techniques to simultaneously record neuronal and astrocytic activity, thus
      enabling the study of multiple ionic currents and in depth investigation of neuro
      glial dialogues. In the current review, we focus on the input such approach has
      provided in the understanding of astrocyte-neuron interactions underlying control
      of synaptic efficacy. 

PMID- 24101895
TI  - A method for the three-dimensional reconstruction of NeurobiotinTM-filled neurons
      and the location of their synaptic inputs.
AB  - Here, we describe a robust method for mapping the number and type of neuro
      chemically distinct synaptic inputs that a single reconstructed neuron receives.
      We have used individual hypoglossal motor neurons filled with Neurobiotin by semi
      loose seal electroporation in thick brainstem slices. These filled motor neurons
      were then processed for excitatory and inhibitory synaptic inputs, using
      immunohistochemical-labeling procedures. For excitatory synapses, we used anti
      VGLUT2 to locate glutamatergic pre-synaptic terminals and anti-PSD-95 to locate
      post-synaptic specializations on and within the surface of these filled motor
      neurons. For inhibitory synapses, we used anti-VGAT to locate GABAergic pre
      synaptic terminals and anti-GABA-A receptor subunit alpha1 to locate the post
      synaptic domain. The Neurobiotin-filled and immuno-labeled motor neuron was then
      processed for optical sectioning using confocal microscopy. The morphology of the
      motor neuron including its dendritic tree and the distribution of excitatory and
      inhibitory synapses were then determined by three-dimensional reconstruction
      using IMARIS software (Bitplane). Using surface rendering, fluorescence
      thresholding, and masking of unwanted immuno-labeling, tools found in IMARIS, we
      were able to obtain an accurate 3D structure of an individual neuron including
      the number and location of its glutamatergic and GABAergic synaptic inputs. The
      power of this method allows for a rapid morphological confirmation of the post
      synaptic responses recorded by patch-clamp prior to Neurobiotin filling. Finally,
      we show that this method can be adapted to super-resolution microscopy
      techniques, which will enhance its applicability to the study of neural circuits
      at the level of synapses. 

PMID- 24101896
TI  - Cognitive control of movement via the cerebellar-recipient thalamus.
AB  - The cognitive control of behavior was long considered to be centralized in
      cerebral cortex. More recently, subcortical structures such as cerebellum and
      basal ganglia have been implicated in cognitive functions as well. The fact that
      subcortico-cortical circuits for the control of movement involve the thalamus
      prompts the notion that activity in movement-related thalamus may also reflect
      elements of cognitive behavior. Yet this hypothesis has rarely been investigated.
      Using the pathways linking cerebellum to cerebral cortex via the thalamus as a
      template, we review evidence that the motor thalamus, together with movement
      related central thalamus have the requisite connectivity and activity to mediate
      cognitive aspects of movement control. 

PMID- 24101897
TI  - Deficits in latent inhibition induced by estradiol replacement are ameliorated by
      haloperidol treatment.
AB  - There are sex differences in the symptomatology of schizophrenia, and in the
      response to antipsychotic treatments. One hallmark symptom of schizophrenia is a
      deficit in selective attention. Selective attention can be measured using a
      latent inhibition (LI) paradigm in humans; LI can be measured in rodents, and is
      used as an animal model of the selective attention deficits observed in
      schizophrenia. In the current experiments LI was used to clarify whether
      selective attention differs between male rats and ovariectomized (OVX) female
      rats receiving different estradiol (E2) replacement regimens. An additional aim
      was to determine whether haloperidol's (HAL) facilitation of LI is enhanced by
      E2. Males and OVX female rats were trained in a conditioned emotional response LI
      paradigm. Females received no E2 replacement, a chronic low dose of E2 via
      silastic capsule, or a high phasic dose of E2 via silastic capsule accompanied by
      E2 (10 ug/kg subcutaneous (SC)) injections every 4th day. Actual plasma levels of
      E2 were determined using an enzyme linked immunosorbent assay. Rats were also
      administered a vehicle treatment, a 0.05 mg/kg, or a 0.1 mg/kg IP injection of
      HAL. Males and OVX females that did not receive E2 replacement both exhibited LI,
      but LI was not observed in the low and high E2 replacement groups. HAL restored
      LI at a lower dose in the females receiving high E2 replacement compared to
      females receiving low E2 replacement, indicating that E2 replacement facilitates
      HAL in restoring LI. 

PMID- 24101898
TI  - What drives successful verbal communication?
AB  - THERE IS A VAST AMOUNT OF POTENTIAL MAPPINGS BETWEEN BEHAVIORS AND INTENTIONS IN
      COMMUNICATION: a behavior can indicate a multitude of different intentions, and
      the same intention can be communicated with a variety of behaviors. Humans
      routinely solve these many-to-many referential problems when producing utterances
      for an Addressee. This ability might rely on social cognitive skills, for
      instance, the ability to manipulate unobservable summary variables to
      disambiguate ambiguous behavior of other agents ("mentalizing") and the drive to
      invest resources into changing and understanding the mental state of other agents
      ("communicative motivation"). Alternatively, the ambiguities of verbal
      communicative interactions might be solved by general-purpose cognitive abilities
      that process cues that are incidentally associated with the communicative
      interaction. In this study, we assess these possibilities by testing which
      cognitive traits account for communicative success during a verbal referential
      task. Cognitive traits were assessed with psychometric scores quantifying
      motivation, mentalizing abilities, and general-purpose cognitive abilities,
      taxing abstract visuo-spatial abilities. Communicative abilities of participants
      were assessed by using an on-line interactive task that required a speaker to
      verbally convey a concept to an Addressee. The communicative success of the
      utterances was quantified by measuring how frequently a number of Evaluators
      would infer the correct concept. Speakers with high motivational and general
      purpose cognitive abilities generated utterances that were more easily
      interpreted. These findings extend to the domain of verbal communication the
      notion that motivational and cognitive factors influence the human ability to
      rapidly converge on shared communicative innovations. 

PMID- 24101901
TI  - Can cellular automata be a representative model for visual perception dynamics?

PMID- 24101899
TI  - Breakfast and cognition: sixteen effects in nine populations, no single recipe.

PMID- 24101900
TI  - Aberrant intrinsic connectivity of hippocampus and amygdala overlap in the fronto
      insular and dorsomedial-prefrontal cortex in major depressive disorder.
AB  - Neuroimaging studies of major depressive disorder (MDD) have consistently
      observed functional and structural changes of the hippocampus (HP) and amygdale
      (AY). Thus, these brain regions appear to be critical elements of the
      pathophysiology of MDD. The HP and AY directly interact and show broad and
      overlapping intrinsic functional connectivity (iFC) to other brain regions.
      Therefore, we hypothesized the HP and AY would show a corresponding pattern of
      aberrant intrinsic connectivity in MDD. Resting-state functional MRI was acquired
      from 21 patients with MDD and 20 healthy controls. beta-Maps of region-of
      interest-based FC for bilateral body of the HP and basolateral AY were used as
      surrogates for iFC of the HP and AY. Analysis of variance was used to compare
      beta-maps between MDD and healthy control groups, and included covariates for age
      and gender as well as gray matter volume of the HP and AY. The HP and AY of MDD
      patient's showed an overlapping pattern of reduced FC to the dorsomedial
      prefrontal cortex and fronto-insular operculum. Both of these regions are known
      to regulate the interactions among intrinsic networks (i.e., default mode,
      central executive, and salience networks) that are disrupted in MDD. These
      results provide the first evidence of overlapping aberrant HP and AY intrinsic
      connectivity in MDD. Our findings suggest that aberrant HP and AY connectivity
      may interact with dysfunctional intrinsic network activity in MDD. 

PMID- 24101902
TI  - Beyond osteogenesis: an in vitro comparison of the potentials of six bone
      morphogenetic proteins.
AB  - Bone morphogenetic proteins (BMPs) other than the clinically available BMP-2 and
      BMP-7 may be useful for improving fracture healing through both increasing
      osteogenesis and creating a favorable healing environment by altering cytokine
      release by endogenous cells. Given the spectrum of potential applications for
      BMPs, the objective of this study was to evaluate various BMPs under a variety of
      conditions to provide further insight into their therapeutic capabilities. The
      alkaline phosphatase (ALP) activity of both C2C12 and human adipose-derived stem
      cells (hASCs) was measured after exposure of increasing doses of recombinant
      human BMP-2, -4, -5, -6, -7, or -9 for 3 and 7 days. BMPs-2, -4, -5, -6, -7, and 
      9 were compared in terms of their ability to affect the release of stromal
      derived factor-1 (SDF-1), vascular endothelial growth factor (VEGF), and basic
      fibroblast growth factor (b-FGF) from human bone marrow stromal cells (hBMSCs).
      Gene expression of ALP, osteocalcin, SDF-1, VEGF, and b-FGF following shRNA
      mediated knockdown of BMP-2 and BMP-6 in hBMSCs or human osteoblasts under
      osteogenic differentiation conditions was also evaluated. Collectively, BMPs-6
      and -9 produced the greatest osteogenic differentiation of C2C12 and hASCs as
      determined by ALP. The hBMSC secretion of SDF-1 was most affected by BMP-5, VEGF
      by BMP-4, and b-FGF by BMP-2. The knockdown of BMP-2 in BMSCs had no effect on
      any of the genes measured whereas BMP-6 knockdown in hBMSCs caused a significant
      increase in VEGF gene expression. BMP-2 and BMP-6 knockdown in human osteoblasts
      caused significant increases in VEGF gene expression and trends toward decreases
      in osteocalcin expression. These findings support efforts to study other BMPs as
      potential bone graft supplements, and to consider combined BMP delivery for
      promotion of multiple aspects of fracture healing. 

PMID- 24101903
TI  - STAT3 modulates cigarette smoke-induced inflammation and protease expression.
AB  - Signal transducer and activator of transcription-3 (STAT3) regulates
      inflammation, apoptosis, and protease expression, which are critical processes
      associated with airway injury and lung tissue destruction. However, the precise
      role of STAT3 in the development of airway diseases such as chronic obstructive
      pulmonary disease (COPD) has not been established. This study shows that
      cigarette smoke activates STAT3 in the lungs of mice. Since cigarette smoke
      activated STAT3 in the lung, we then evaluated how the loss of STAT3 would impact
      on smoke-mediated lung inflammation, protease expression, and apoptosis.
      STAT3(+/+) and STAT3(-/-) mice were exposed to 8 days of cigarette smoke.
      Compared to the STAT3(+/+) mice bronchoalveolar lavage fluid (BALF) cellularity
      was significantly elevated in the STAT3(-/-) mice both before and after cigarette
      smoke exposure, with the increase in cells primarily macrophages. In addition,
      smoke exposure induced significantly higher BALF protein levels of Interleukin
      1alpha (IL-1alpha), and monocyte chemotactic protein-1 (MCP-1) and higher tissue
      expression of keratinocyte chemoattractant (KC) in the STAT3(-/-) mice. Lung mRNA
      expression of MMP-12 was increased in STAT3(-/-) at baseline. However, the smoke
      induced increase in MMP-10 expression seen in the STAT3(+/+) mice was not
      observed in the STAT3(-/-) mice. Moreover, lung protein levels of the anti
      inflammatory proteins SOCS3 and IL-10 were markedly lower in the STAT3(-/-) mice
      compared to the STAT3(+/+) mice. Lastly, apoptosis, as determined by caspase 3/7
      activity assay, was increased in the STAT3(-/-) at baseline to levels comparable
      to those observed in the smoke-exposed STAT3(+/+) mice. Together, these results
      indicate that the smoke-mediated induction of lung STAT3 activity may play a
      critical role in maintaining normal lung homeostasis and function. 

PMID- 24101904
TI  - Molecular mechanisms of renal and extrarenal manifestations caused by
      inactivation of the electrogenic Na(+)-HCO3 (-) cotransporter NBCe1.
AB  - The electrogenic Na(+)-HCO3 (-) cotransporter NBCe1 plays an essential role in
      bicarbonate absorption from renal proximal tubules, but also mediates the other
      biological processes in extrarenal tissues such as bicarbonate secretion from
      pancreatic ducts, maintenance of tissue homeostasis in eye, enamel maturation in
      teeth, or local pH regulation in synapses. Homozygous mutation in NBCe1 cause
      proximal renal tubular acidosis (pRTA) associated with extrarenal manifestations
      such as short stature, ocular abnormalities, enamel abnormalities, and migraine.
      Functional analyses of NBCe1 mutants using different expression systems suggest
      that at least a 50% reduction of the transport activity may be required to induce
      severe pRTA. In addition to functional impairments, some NBCe1 mutants show
      trafficking defects. Some of the pRTA-related NBCe1 mutants showing the
      cytoplasmic retention have been shown to exert a dominant negative effect through
      hetero-oligomer complexes with wild-type NBCe1 that may explain the occurrence of
      extrarenal manifestations in the heterozygous carries of NBCe1 mutations. Both
      NBCe1 knockout (KO) and W516X knockin (KI) mice showed very severe pRTA and
      reproduced most of the clinical manifestations observed in human pRTA patients.
      Functional analysis on isolated renal proximal tubules from W516X KI mice
      directly confirmed the indispensable role of NBCe1 in bicarbonate absorption from
      this nephron segment. In this review, we will focus on the molecular mechanisms
      underling the renal and extrarenal manifestations caused by NBCe1 inactivation. 

PMID- 24101905
TI  - The effect of carbonic anhydrase IX on focal contacts during cell spreading and
      migration.
AB  - Carbonic anhydrase IX is a hypoxia-induced transmembrane enzyme linked with solid
      tumors. It catalyzes the reversible hydration of CO2 providing bicarbonate ions
      for intracellular neutralization and protons for extracellular acidosis, thereby
      supporting tumor cell survival and invasiveness. CA IX is the only human CA
      isoform containing the proteoglycan (PG) domain in its extracellular part. The PG
      domain appears to enhance the catalytic activity of CA IX and mediate its binding
      to the extracellular matrix. Moreover, manipulation of the CA IX level by siRNA
      or overexpression modulates cell adhesion pathway so that in the presence of CA
      IX, cells display an increased rate of adhesion and spreading. Here we show that
      deletion of the PG domain as well as treatment with the PG-binding monoclonal
      antibody M75 can impair this CA IX effect. Accordingly, CA IX-expressing cells
      show more prominent and elongated maturing paxillin-stained focal contacts (FC)
      than CA IX-negative controls, proving the role of CA IX in cell spreading.
      However, during active cell movement, CA IX is relocalized to lamellipodia and
      improves migration via its catalytic domain. Thus, we examined the influence of
      CA IX on FC turnover in these structures. While the lamellipodial regions lacking
      CA IX display dash-like adhesions, the CA IX-enriched neighboring regions exhibit
      dynamic dot-like FCs. These results suggest that CA IX can promote initial
      adhesion through its PG domain, but at the same time it facilitates formation of
      nascent adhesions at the leading edge of moving cells. Thereby it may allow for
      transmission of large forces and enhanced migration rate, presumably through
      catalytic activity and impact of pHe on FC dynamics. Thus, we provide the first
      evidence that CA IX protein localizes directly in focal adhesion (FA) structures
      and propose its functional relationship with the proteins involved in the
      regulation of FC turnover and maturation. 

PMID- 24101906
TI  - The STAT3-Ser/Hes3 signaling axis: an emerging regulator of endogenous
      regeneration and cancer growth.
AB  - Stem cells, by definition, are able to both self-renew (give rise to more cells
      of their own kind) and demonstrate multipotential (the ability to differentiate
      into multiple cell types). To accommodate this unique dual ability, stem cells
      interpret signal transduction pathways in specialized ways. Notable examples
      include canonical and non-canonical branches of the Notch signaling pathway, with
      each controlling different downstream targets (e.g., Hes1 vs. Hes3) and promoting
      either differentiation or self-renewal. Similarly, stem cells utilize STAT3
      signaling uniquely. Most mature cells studied thus far rely on tyrosine
      phosphorylation (STAT3-Tyr) to promote survival and growth; in contrast, STAT3
      Tyr induces the differentiation of neural stem cells (NSCs). NSCs use an
      alternative phosphorylation site, STAT3-Ser, to regulate survival and growth, a
      site that is largely redundant for this function in most other cell types. STAT3
      Ser regulates Hes3, and together they form a convergence point for several
      signals, including Notch, Tie2, and insulin receptor activation. Disregulation
      and manipulation of the STAT3-Ser/Hes3 signaling pathway is important in both
      tumorigenesis and regenerative medicine, and worthy of extensive study. 

PMID- 24101907
TI  - Extracting salient sublexical units from written texts: "Emophon," a corpus-based
      approach to phonological iconicity.
AB  - A GROWING BODY OF LITERATURE IN PSYCHOLOGY, LINGUISTICS, AND THE NEUROSCIENCES
      HAS PAID INCREASING ATTENTION TO THE UNDERSTANDING OF THE RELATIONSHIPS BETWEEN
      PHONOLOGICAL REPRESENTATIONS OF WORDS AND THEIR MEANING: a phenomenon also known
      as phonological iconicity. In this article, we investigate how a text's intended
      emotional meaning, particularly in literature and poetry, may be reflected at the
      level of sublexical phonological salience and the use of foregrounded elements.
      To extract such elements from a given text, we developed a probabilistic model to
      predict the exceeding of a confidence interval for specific sublexical units
      concerning their frequency of occurrence within a given text contrasted with a
      reference linguistic corpus for the German language. Implementing this model in a
      computational application, we provide a text analysis tool which automatically
      delivers information about sublexical phonological salience allowing researchers,
      inter alia, to investigate effects of the sublexical emotional tone of texts
      based on current findings on phonological iconicity. 

PMID- 24101908
TI  - Effects of voice on emotional arousal.
AB  - Music is a powerful medium capable of eliciting a broad range of emotions.
      Although the relationship between language and music is well documented,
      relatively little is known about the effects of lyrics and the voice on the
      emotional processing of music and on listeners' preferences. In the present
      study, we investigated the effects of vocals in music on participants' perceived
      valence and arousal in songs. Participants (N = 50) made valence and arousal
      ratings for familiar songs that were presented with and without the voice. We
      observed robust effects of vocal content on perceived arousal. Furthermore, we
      found that the effect of the voice on enhancing arousal ratings is independent of
      familiarity of the song and differs across genders and age: females were more
      influenced by vocals than males; furthermore these gender effects were enhanced
      among older adults. Results highlight the effects of gender and aging in emotion
      perception and are discussed in terms of the social roles of music. 

PMID- 24101909
TI  - Mind wandering in text comprehension under dual-task conditions.
AB  - In two experiments, subjects responded to on-task probes while reading under dual
      task conditions. The secondary task was to monitor the text for occurrences of
      the letter e. In Experiment 1, reading comprehension was assessed with a multiple
      choice recognition test; in Experiment 2, subjects recalled the text. In both
      experiments, the secondary task replicated the well-known "missing-letter effect"
      in which detection of e's was less effective for function words and the word
      "the." Letter detection was also more effective when subjects were on task, but
      this effect did not interact with the missing-letter effect. Comprehension was
      assessed in both the dual-task conditions and in control single-task conditions.
      In the single-task conditions, both recognition (Experiment 1) and recall
      (Experiment 2) was better when subjects were on task, replicating previous
      research on mind wandering. Surprisingly, though, comprehension under dual-task
      conditions only showed an effect of being on task when measured with recall;
      there was no effect on recognition performance. Our interpretation of this
      pattern of results is that subjects generate responses to on-task probes on the
      basis of a retrospective assessment of the contents of working memory. Further,
      we argue that under dual-task conditions, the contents of working memory is not
      closely related to the reading processes required for accurate recognition
      performance. These conclusions have implications for models of text comprehension
      and for the interpretation of on-task probe responses. 

PMID- 24101910
TI  - Behavioral laterality of the brain: support for the binary construct of hemisity.
AB  - THREE TERMS DEFINE BRAIN BEHAVIORAL LATERALITY: hemispheric dominance identifies
      the cerebral hemisphere producing one's first language. Hemispheric asymmetry
      locates the brain side of non-language skills. A third term is needed to describe
      a person's binary thinking, learning, and behaving styles. Since the 1950s split
      brain studies, evidence has accumulated that individuals with right or left brain
      behavioral orientations (RPs or LPs) exist. Originally, hemisphericity sought,
      but failed, to confirm the existence of such individual differences, due to its
      assertion that each individual lay somewhere on a gradient between competing left
      and right brain extremes. Recently, hemisity, a more accurate behavioral
      laterality context, has emerged. It posits that one's behavioral laterality is
      binary: i.e., inherently either right or left brain-oriented. This insight
      enabled the quantitative determination of right or left behavioral laterality of
      thousands of subjects. MRI scans of right and left brain-oriented groups revealed
      two neuroanatomical differences. The first was an asymmetry of an executive
      element in the anterior cingulate cortex (ACC). This provided hemisity both a
      rationale and a primary standard. RPs and LPs gave opposite answers to many
      behavioral preference "either-or," forced choice questions. This showed that
      several sex vs. hemisity traits are being conflated by society. Such was
      supported by the second neuroanatomical difference between the hemisity subtypes,
      that RPs of either sex had up to three times larger corpus callosi than LPs.
      Individuals of the same hemisity but opposite sex had more personality traits in
      common than those of the same sex but different hemisity. Although hemisity
      subtypes were equally represented in the general population, the process of
      higher education and career choice caused substantial hemisity sorting among the
      professions. Hemisity appears to be a valid and promising area for quantitative
      research of behavioral laterality.

PMID- 24101911
TI  - The cognitive processes underlying affective decision-making predicting
      adolescent smoking behaviors in a longitudinal study.
AB  - This study investigates the relationship between three different cognitive
      processes underlying the Iowa Gambling Task (IGT) and adolescent smoking
      behaviors in a longitudinal study. We conducted a longitudinal study of 181
      Chinese adolescents in Chengdu City, China. The participants were followed from
      10th to 11th grade. When they were in the 10th grade (Time 1), we tested these
      adolescents' decision-making using the IGT and working memory capacity using the
      Self-ordered Pointing Test (SOPT). Self-report questionnaires were used to assess
      school academic performance and smoking behaviors. The same questionnaires were
      completed again at the 1-year follow-up (Time 2). The Expectancy-Valence (EV)
      Model was applied to distill the IGT performance into three different underlying
      psychological components: (i) a motivational component which indicates the
      subjective weight the adolescents assign to gains vs. losses; (ii) a learning
      rate component which indicates the sensitivity to recent outcomes vs. past
      experiences; and (iii) a response component which indicates how consistent the
      adolescents are between learning and responding. The subjective weight to gains
      vs. losses at Time 1 significantly predicted current smokers and current smoking
      levels at Time 2, controlling for demographic variables and baseline smoking
      behaviors. Therefore, by decomposing the IGT into three different psychological
      components, we found that the motivational process of weight gain vs. losses may
      serve as a neuropsychological marker to predict adolescent smoking behaviors in a
      general youth population. 

PMID- 24101912
TI  - Awareness as observational heterarchy.
AB  - Libet et al. (1983) revealed that brain activity precedes conscious intention.
      For convenience in this study, we divide brain activity into two parts: a
      conscious field (CF) and an unconscious field (UF). Most studies have assumed a
      comparator mechanism or an illusion of CF and discuss the difference of
      prediction and postdiction. We propose that problems to be discussed here are a
      twisted sense of agency between CF and UF, and another definitions of prediction
      and postdiction in a mediation process for the twist. This study specifically
      examines the definitions throughout an observational heterarchy model based on
      internal measurement. The nature of agency must be emergence that involves
      observational heterarchy. Consequently, awareness involves processes having
      duality in the sense that it is always open to the world (postdiction) and that
      it also maintains self robustly (prediction). 

PMID- 24101913
TI  - Attentional decoupling while pursuing intentions: a form of mind wandering?
AB  - In the current study, participants performed an ongoing lexical decision task
      (LDT) in which they had to classify letter strings as words or non-words. In
      intention conditions, they also had to encode a postponed intention to remember
      to make a different response if a pre-specified cue appeared. Attempting to
      replicate an important finding from Cohen et al. (2008), the interest was in
      examining how varying cognitive load associated with an intention influences
      attention to the ongoing task (measured by reaction times). Typically,
      disengaging from a primary task is perceived as negative as it can lead to
      performance decrements, however, if disengaging from a primary task helps one to
      accomplish a desired future goal, then these attentional shifts may in fact be
      constructive. Results replicated those of Cohen et al. (2008) and showed that
      participants were very flexible in how they managed attention in the ongoing LDT.
      Reaction time costs emerged when cognitive load was high and solely for word
      trials (i.e., not for non-word trials). The implications for mind wandering are
      that, while our attention may wander when stimuli are present that trigger a
      suspended or unfulfilled goal, we are better able to stay on task when the
      stimuli are less goal relevant. Therefore, the decoupling process (e.g., Schooler
      et al., 2011) might be initiated when postponed goals are accompanied by a high
      degree of cognitive load and when external stimuli are present that relate to
      that goal. 

PMID- 24101914
TI  - Of Timescales, Animal Models, and Human Disease: The 50th Anniversary of C.
      elegans as a Biological Model.

PMID- 24101915
TI  - Development and application of specific cytokine assays in tissue samples from a
      bottlenose dolphin with hyperinsulinemia.
AB  - Chronic inflammation has been associated with insulin resistance and type 2
      diabetes (T2D) in humans. Postmortem hepatic and splenic tissue from a 46-year
      old geriatric male bottlenose dolphin (Tursiops truncatus) with insulin
      resistance (chronic hyperinsulinemia with hyperglycemia), chronic inflammation
      (white blood cell count greater than 12,000 cells/MUL), and mild fatty liver
      disease was evaluated for elevated pro-inflammatory mediators. Cytokine mRNA
      expression in postmortem hepatic and splenic tissue, as determined by real-time
      PCR, included an array of cytokines: TGF-beta, TNF-alpha, IFN-gamma, IL-2, IL-4,
      IL-10, IL-12p40, IL-13, and IL-18. Values from this dolphin were compared to a
      younger reference dolphin with no known chronic metabolic perturbations or
      inflammation. Levels of TGF-beta, TNF-alpha, and IL-4 were higher in the case
      dolphin's liver compared to that of the reference dolphin. In the case dolphin's
      spleen, IL-10 and IFN-gamma mRNA was upregulated while IL-4 was less than the
      reference dolphin. IL-18 and IL-13 were upregulated in both tissues. Fluorescent
      immunohistochemistry (IHC) utilized the following antibodies: anti-porcine IL-6,
      anti-bovine IFN-gamma, IL-4, and IL-10, anti-human TGF-beta, anti-ovine IL-1beta,
      and anti-dolphin IL-8. Fluorescent IHC in spleen from the case dolphin revealed
      staining of IL-4, IL-6, IL-8, and TGF-beta throughout the tissue. IL-10 and IFN
      gamma were seen to predominate in areas surrounding the follicles of splenic
      tissue. This is the first characterization of cytokine levels in dolphin hepatic
      and splenic tissue. While there are limitations to a case study, this report of
      inflammatory biomarkers in tissues of a dolphin with insulin resistance and fatty
      liver disease are similar to those observed in human patients. 

PMID- 24101916
TI  - FunGene: the functional gene pipeline and repository.
AB  - Ribosomal RNA genes have become the standard molecular markers for microbial
      community analysis for good reasons, including universal occurrence in cellular
      organisms, availability of large databases, and ease of rRNA gene region
      amplification and analysis. As markers, however, rRNA genes have some significant
      limitations. The rRNA genes are often present in multiple copies, unlike most
      protein-coding genes. The slow rate of change in rRNA genes means that multiple
      species sometimes share identical 16S rRNA gene sequences, while many more
      species share identical sequences in the short 16S rRNA regions commonly
      analyzed. In addition, the genes involved in many important processes are not
      distributed in a phylogenetically coherent manner, potentially due to gene loss
      or horizontal gene transfer. While rRNA genes remain the most commonly used
      markers, key genes in ecologically important pathways, e.g., those involved in
      carbon and nitrogen cycling, can provide important insights into community
      composition and function not obtainable through rRNA analysis. However, working
      with ecofunctional gene data requires some tools beyond those required for rRNA
      analysis. To address this, our Functional Gene Pipeline and Repository (FunGene;
      http://fungene.cme.msu.edu/) offers databases of many common ecofunctional genes
      and proteins, as well as integrated tools that allow researchers to browse these
      collections and choose subsets for further analysis, build phylogenetic trees,
      test primers and probes for coverage, and download aligned sequences. Additional
      FunGene tools are specialized to process coding gene amplicon data. For example,
      FrameBot produces frameshift-corrected protein and DNA sequences from raw reads
      while finding the most closely related protein reference sequence. These tools
      can help provide better insight into microbial communities by directly studying
      key genes involved in important ecological processes. 

PMID- 24101918
TI  - Helminth defence molecules-immunomodulators designed by parasites!

PMID- 24101919
TI  - Dynamical and Mechanistic Reconstructive Approaches of T Lymphocyte Dynamics:
      Using Visual Modeling Languages to Bridge the Gap between Immunologists,
      Theoreticians, and Programmers.
AB  - Dynamic modeling of lymphocyte behavior has primarily been based on populations
      based differential equations or on cellular agents moving in space and
      interacting each other. The final steps of this modeling effort are expressed in
      a code written in a programing language. On account of the complete lack of
      standardization of the different steps to proceed, we have to deplore poor
      communication and sharing between experimentalists, theoreticians and
      programmers. The adoption of diagrammatic visual computer language should however
      greatly help the immunologists to better communicate, to more easily identify the
      models similarities and facilitate the reuse and extension of existing software
      models. Since immunologists often conceptualize the dynamical evolution of immune
      systems in terms of "state-transitions" of biological objects, we promote the use
      of unified modeling language (UML) state-transition diagram. To demonstrate the
      feasibility of this approach, we present a UML refactoring of two published
      models on thymocyte differentiation. Originally built with different modeling
      strategies, a mathematical ordinary differential equation-based model and a
      cellular automata model, the two models are now in the same visual formalism and
      can be compared. 

PMID- 24101917
TI  - From antimicrobial to anticancer peptides. A review.
AB  - Antimicrobial peptides (AMPs) are part of the innate immune defense mechanism of
      many organisms. Although AMPs have been essentially studied and developed as
      potential alternatives for fighting infectious diseases, their use as anticancer
      peptides (ACPs) in cancer therapy either alone or in combination with other
      conventional drugs has been regarded as a therapeutic strategy to explore. As
      human cancer remains a cause of high morbidity and mortality worldwide, an urgent
      need of new, selective, and more efficient drugs is evident. Even though ACPs are
      expected to be selective toward tumor cells without impairing the normal body
      physiological functions, the development of a selective ACP has been a challenge.
      It is not yet possible to predict antitumor activity based on ACPs structures.
      ACPs are unique molecules when compared to the actual chemotherapeutic arsenal
      available for cancer treatment and display a variety of modes of action which in
      some types of cancer seem to co-exist. Regardless the debate surrounding the
      definition of structure-activity relationships for ACPs, great effort has been
      invested in ACP design and the challenge of improving effective killing of tumor
      cells remains. As detailed studies on ACPs mechanisms of action are crucial for
      optimizing drug development, in this review we provide an overview of the
      literature concerning peptides' structure, modes of action, selectivity, and
      efficacy and also summarize some of the many ACPs studied and/or developed for
      targeting different solid and hematologic malignancies with special emphasis on
      the first group. Strategies described for drug development and for increasing
      peptide selectivity toward specific cells while reducing toxicity are also
      discussed. 

PMID- 24101920
TI  - Thermodynamics of Peptide-MHC Class II Interactions: Not all Complexes are
      Created Equal.
AB  - The adaptive immune response begins when CD4+ T cells recognize antigenic
      peptides bound to class II molecules of the Major Histocompatibility Complex
      (MHCII). The interaction between peptides and MHCII has been historically
      interpreted as a rigid docking event. However, this model has been challenged by
      the evidence that conformational flexibility plays an important role in peptide
      MHCII complex formation. Thermodynamic analysis of the binding reaction suggests
      a model of complexation in which the physical-chemical nature of the peptide
      determines the variability in flexibility of the substates in the peptide-MHC
      conformational ensemble. This review discusses our understanding of the
      correlation between thermodynamics of peptide binding and structural features of
      the resulting complex as well as their impact on HLA-DM activity and on our
      ability to predict MHCII-restricted epitopes. 

PMID- 24101921
TI  - Activation of the Interferon Pathway is Dependent Upon Autoantibodies in African
      American SLE Patients, but Not in European-American SLE Patients.
AB  - BACKGROUND: In systemic lupus erythematosus (SLE), antibodies directed at RNA
      binding proteins (anti-RBP) are associated with high serum type I interferon
      (IFN), which plays an important role in SLE pathogenesis. African-Americans (AA)
      are more likely to develop SLE, and SLE is also more severe in this population.
      We hypothesized that peripheral blood gene expression patterns would differ
      between AA and European-American (EA) SLE patients, and between those with anti
      RBP antibodies and those who lack these antibodies. METHODS: Whole blood RNA from
      33 female SLE patients and 16 matched female controls from AA and EA ancestral
      backgrounds was analyzed on Affymetrix Gene 1.0 ST gene expression arrays.
      Ingenuity Pathway Analysis was used to compare the top differentially expressed
      canonical pathways amongst the sample groups. An independent cohort of 116 SLE
      patients was used to replicate findings using quantitative real-time PCR (qPCR).
      RESULTS: Both AA and EA patients with positive anti-RBP antibodies showed over
      expression of similar IFN-related canonical pathways, such as IFN Signaling (P =
      1.3 * 10(-7) and 6.3 * 10(-11) in AA vs. EA respectively), Antigen Presenting
      Pathway (P = 1.8 * 10(-5) and 2.5 * 10(-6)), and a number of pattern recognition
      receptor pathways. In anti-RBP negative (RBP-) patients, EA subjects demonstrated
      similar IFN-related pathway activation, whereas no IFN-related pathways were
      detected in RBP-AA patients. qPCR validation confirmed similar results.
      CONCLUSION: Our data show that IFN-induced gene expression is completely
      dependent on the presence of autoantibodies in AA SLE patients but not in EA
      patients. This molecular heterogeneity suggests differences in IFN-pathway
      activation between ancestral backgrounds in SLE. This heterogeneity may be
      clinically important, as therapeutics targeting this pathway are being developed.

PMID- 24101922
TI  - How unique is the low oxygen response? An analysis of the anaerobic response
      during germination and comparison with abiotic stress in rice and Arabidopsis.
AB  - Plants face a variety of environmental stresses and have evolved molecular
      mechanisms to survive these challenges. One of these stresses is low oxygen
      conditions, which can occur under flooding conditions. Rice (Oryza sativa) is
      somewhat unique for its ability to tolerate and even germinate under low to no
      oxygen conditions. In this study, we examined global transcriptomic responses
      over the course of germination and in response to low oxygen and other abiotic
      stress in rice and Arabidopsis (Arabidopsis thaliana). Over 150 microarray
      datasets were analyzed in parallel to determine just how unique the low oxygen
      response is in rice. Comparison of aerobic germination in rice and Arabidopsis,
      with anaerobic germination in rice revealed conserved transcriptomic responses
      that are not only conserved across both species but also occur in the absence of
      oxygen in rice. Thus, these genes may represent functions necessary for the
      developmental progression of germination, whether or not oxygen is present in
      rice. Analysis of genes that responded differently in rice compared to
      Arabidopsis revealed responses specific to anaerobic germination in rice,
      including the down-regulation of genes encoding redox functions and up-regulation
      of receptor kinases. Comparison of a range of hypoxia/anoxia studies within and
      across Arabidopsis and rice revealed both conserved and species specific changes
      in gene expression (e.g., Arabidopsis specific up-regulation of WRKYs and rice
      specific down-regulation of heme), unveiling unique transcriptomic signatures of
      the low oxygen response. Lastly, a comparison of the low oxygen response with
      cold, salt, drought and heat stress revealed some similarity with the response to
      heat stress in Arabidopsis, which was not seen in rice. Comparison of these heat
      responsive, abiotic stress marker genes in Arabidopsis with their rice orthologs
      revealed that while low oxygen may be perceived as an abiotic stress in
      Arabidopsis, this is not the case in rice. 

PMID- 24101923
TI  - The clinical investigation of disparity of utility values associated with
      gallstone disease: a pilot study.
AB  - Purpose. The utility evaluation was an effective method to incorporate all of the
      contributing variables for multiple diseases into one outcome measure. A cross
      sectional study was conducted to assess the utility values associated with
      varying states of gallstone disease among outpatient clinics participants at a
      teaching hospital in Taipei, Taiwan. Methods. The utility values were measured by
      using time trade-off method. A total of 120 outpatient clinics participants (30
      subjects with no gallstone disease, 30 subjects with single stone, 30 subjects
      with multiple stones, and 30 subjects with cholecystectomy) evaluated utility
      values from January 1, 2006 to December 31, 2006. The diagnosis of gallstone
      disease was performed by a panel of specialists using ultrasound sonography.
      Results. The overall mean utility value was 0.89 +/- 0.13 (95% CI: 0.87-0.91)
      indicating that study participants were willing to trade about 11% (95% CI: 9
      13%) of their remaining life in return for being free of gallstone disease
      perpetually. The significant associated factors of utility values based on the
      multiple linear regression analysis were older age and different degrees of
      gallstone disease. Conclusion. Our results found that in addition to older age,
      multiple stones and cholecystectomy could influence utility values from the
      patient's preference-based viewpoint. 

PMID- 24101925
TI  - Chronic Mild Hyperglycemia in GCK-MODY Patients Does Not Increase Carotid Intima
      Media Thickness.
AB  - Aim. GCK-MODY is an autosomal dominant form of diabetes caused by heterozygous
      mutations in the glucokinase gene leading to a lifelong mild hyperglycemia. The
      risk of macrovascular complications is considered low, but studies are limited.
      We, therefore, investigated the carotid intima-media thickness (CIMT) as an
      indicator of macrovascular complications in a group of patients with GCK-MODY.
      Methods. Twenty-seven GCK mutation carriers and 24 controls recruited among their
      first-degree relatives were compared, all aging over 35 years. The CIMT was
      tested using a high-resolution B-mode carotid ultrasonography. Medical history,
      anthropometry, and biochemical blood workup were obtained. Results. The mean CIMT
      was 0.707 +/- 0.215 mm (mean +/- SD) in GCK mutation carriers and 0.690 +/- 0.180
      mm in control individuals. When adjusted for age, gender, and family status, the
      estimated mean difference in CIMT between the two groups increased to 0.049 mm (P
      = 0.19). No difference was detected for other characteristics, with the exception
      of fasting blood glucose (GCK-MODY 7.6 mmol/L +/- 1.2 (136.4 mg/dL); controls 5.3
      mmol/L +/- 0.3 (95.4 mg/dL); P < 0.0001) and glycated hemoglobin HbA1c (GCK-MODY
      6.9% +/- 1.0%, 52 mmol/mol +/- 10; controls 5.7% +/- 0.4%, 39 mmol/mol +/- 3; P <
      0.0001). The frequency of myocardial infarction and ischemic stroke did not
      differ between groups. Conclusion. Our data indicate that the persistent
      hyperglycemia in GCK-MODY is associated with a low risk of developing diabetic
      macrovascular complications. 

PMID- 24101924
TI  - Role of GnRH Neurons and Their Neuronal Afferents as Key Integrators between Food
      Intake Regulatory Signals and the Control of Reproduction.
AB  - Reproductive function is regulated by a plethora of signals that integrate
      physiological and environmental information. Among others, metabolic factors are
      key components of this circuit since they inform about the propitious timing for
      reproduction depending on energy availability. This information is processed
      mainly at the hypothalamus that, in turn, modulates gonadotropin release from the
      pituitary and, thereby, gonadal activity. Metabolic hormones, such as leptin,
      insulin, and ghrelin, act as indicators of the energy status and convey this
      information to the reproductive axis regulating its activity. In this review, we
      will analyse the central mechanisms involved in the integration of this metabolic
      information and their contribution to the control of the reproductive function.
      Particular attention will be paid to summarize the participation of GnRH, Kiss1,
      NPY, and POMC neurons in this process and their possible interactions to
      contribute to the metabolic control of reproduction. 

PMID- 24101926
TI  - Role of the endocannabinoid system in the central regulation of nonmammalian
      vertebrate reproduction.
AB  - The endocannabinoid system (ECS) has a well-documented pivotal role in the
      control of mammalian reproductive functions, by acting at multiple levels, that
      is, central (CNS) and local (gonads) levels. Since studies performed in animal
      models other than mammals might provide further insight into the biology of these
      signalling molecules, in the present paper we review the comparative data
      pointing toward the endocannabinoid involvement in the reproductive control of
      non-mammalian vertebrates, focussing in particular on the central regulation of
      teleost and amphibian reproduction. The morphofunctional distribution of brain
      cannabinoid receptors will be discussed in relation to other crucial signalling
      molecules involved in the control of reproductive functions, such as GnRH,
      dopamine, aromatase, and pituitary gonadotropins. 

PMID- 24101927
TI  - Silver nanoparticles and mitochondrial interaction.
AB  - Nanotechnology has gone through a period of rapid growth, thus leading to the
      constant increase in the application of engineered nanomaterials in daily life.
      Several different types of nanoparticles have been engineered to be employed in a
      wide array of applications due to their high surface to volume ratio that leads
      to unique physical and chemical properties. So far, silver nanoparticles (AgNps)
      have been used in many more different medical devices than any other
      nanomaterial, mainly due to their antimicrobial properties. Despite the promising
      advantages posed by using AgNps in medical applications, the possible health
      effects associated with the inevitable human exposure to AgNps have raised
      concerns as to their use since a clear understanding of their specific
      interaction with biological systems has not been attained yet. In light of such
      consideration, aim of the present work is the morphological analysis of the
      intracellular behavior of AgNps with a diameter of 10 nm, with a special
      attention to their interaction with mitochondria. 

PMID- 24101928
TI  - A Four-Year Monocentric Study of the Complications of Third Molars Extractions
      under General Anesthesia: About 2112 Patients.
AB  - Introduction. The aim of this study was to assess the complications resulting
      from third molar extraction under general anesthesia. Material and Methods. The
      retrospective study included all patients who underwent impacted third molars
      extraction from January 2008 until December 2011. 7659 third molars were
      extracted for 2112 patients. Postoperative complications were retrieved from
      medical files. Results. No complications were related to general anesthesia. The
      most frequent postoperative complication was infection (7.15%). Lingual nerve
      injuries affected 1.8% of the patients. All of them were transient and were not
      related to tooth section. Inferior alveolar nerve injuries were reported in 0.4%
      of the cases. 95.8% of these patients were admitted for one-day ambulatory care,
      and only two patients were readmitted after discharge from hospital. Discussion.
      This surgical technique offers comfort for both surgeons and patients. Risks are
      only linked to the surgical procedure as we observed no complication resulting
      from general anesthesia. One-day hospitalization offers a good balance between
      comfort, security, and cost. The incidence of complications is in agreement with
      the literature data, especially regarding pain, edema, and infectious and nervous
      complications. It is of utmost importance to discuss indications with patients,
      and to provide them with clear information. 

PMID- 24101929
TI  - Craniomandibular disorders and mandibular reference position in orthodontic
      treatment.
AB  - The aim of this paper is to bring into focus the literature on the choice of the
      mandibular reference position in orthodontic treatment; of a particular reference
      to this paper is intercuspal position, centric relation position, or therapeutic
      position. To give a comprehensive account of the literature review on
      craniomandibular disorders (CMD), we have relied on books and articles using both
      Google Scholar and PubMed. Selection criteria included a combination of Mesh and
      type of article. Article classification was made by two authors, using the
      following structure outline: prevalence of craniomandibular disorders, its
      etiology and pathophysiology, occlusion and craniomandibular disorders,
      orthodontic treatment and CMD, and the mandibular reference position in
      orthodontics. An important conclusion that emerged from the present literature
      review is that CMD do not seem to be directly related to orthodontic treatment,
      and their appearance cannot be predicted or prevented by any means. Therefore,
      orthodontists must adopt a mandibular reference suitable to their patients and
      which best respects the balance existing in the stomatognathic system. 

PMID- 24101930
TI  - The use of porous scaffold as a tumor model.
AB  - Background. Human cancer is a three-dimensional (3D) structure consisting of
      neighboring cells, extracellular matrix, and blood vessels. It is therefore
      critical to mimic the cancer cells and their surrounding environment during in
      vitro study. Our aim was to establish a 3D cancer model using a synthetic
      composite scaffold. Methods. High-density low-volume seeding was used to promote
      attachment of a non-small-cell lung cancer cell line (NCI-H460) to scaffolds.
      Growth patterns in 3D culture were compared with those of monolayers.
      Immunohistochemistry was conducted to compare the expression of Ki67, CD44, and
      carbonic anhydrase IX. Results. NCI-H460 readily attached to the scaffold without
      surface pretreatment at a rate of 35% from a load of 1.5 * 10(6) cells. Most
      cells grew vertically to form clumps along the surface of the scaffold, and cell
      morphology resembled tissue origin; 2D cultures exhibited characteristics of
      adherent epithelial cancer cell lines. Expression patterns of Ki67, CD44, and CA
      IX varied markedly between 3D and monolayer cultures. Conclusions. The behavior
      of cancer cells in our 3D model is similar to tumor growth in vivo. This model
      will provide the basis for future study using 3D cancer culture. 

PMID- 24101931
TI  - Aberrant alternative splicing is another hallmark of cancer.
AB  - The vast majority of human genes are alternatively spliced. Not surprisingly,
      aberrant alternative splicing is increasingly linked to cancer. Splice isoforms
      often encode proteins that have distinct and even antagonistic properties. The
      abnormal expression of splice factors and splice factor kinases in cancer changes
      the alternative splicing of critically important pre-mRNAs. Aberrant alternative
      splicing should be added to the growing list of cancer hallmarks. 

PMID- 24101932
TI  - Respiratory review of 2013: pulmonary thromboembolism.
AB  - Pulmonary embolism (PE), which can originate as a consequence of deep vein
      thrombosis (DVT), is the most frequent and potentially fatal venous
      thromboembolic event. Despite the fact that the incidence of venous
      thromboembolism (VTE) in Asians is lower than that in the Western populations, a
      recent epidemiologic study demonstrates an increasing incidence of VTE in the
      Korean population. Anticoagulants, including low molecular weight heparin (LMWH)
      and vitamin K antagonist (VKAs), have been the main treatments for PE, however,
      recently new oral anticoagulants (NOACs) were introduced. We will review how well
      patients with PE can be managed with the existing anticoagulants and NOACs along
      with the time span of treatment, which still pose some challenges for clinicians.

PMID- 24101933
TI  - Neuroendocrine differentiation in acquired resistance to epidermal growth factor
      receptor tyrosine kinase inhibitor.
AB  - BACKGROUND: Small cell lung cancer (SCLC) transformation during epidermal growth
      factor receptor tyrosine kinase inhibitor (EGFR-TKI) treatment in lung cancer has
      been suggested as one of possible resistance mechanisms. METHODS: We evaluated
      whether SCLC transformation or neuroendocrine (NE) differentiation can be found
      in the cell line model. In addition, we also investigated its effect on responses
      to conventional chemotherapeutic drugs of the SCLC treatment. RESULTS: Resistant
      cell lines to various kinds of EGFR-TKIs such as gefitinib, erlotinib, CL-387,785
      and ZD6474 with A549, PC-9 and HCC827 lung adenocarcinoma cell lines were
      established. Among them, two resistant cell lines, A549/GR (resistant to
      gefitinib) and PC-9/ZDR (resistant to ZD6474) showed increased expressions of
      CD56 while increased synaptophysin, Rb, p16 and poly(ADP-ribose) polymerase were
      found only in A549/GR in western blotting, suggesting that NE differentiation
      occurred in A549/GR. A549/GR cells were more sensitive to etoposide and
      cisplatin, chemotherapeutic drugs for SCLC, compared to parental cells. Treatment
      with cAMP and IBMX induced synaptophysin and chromogranin A expression in A549
      cells, which also made them more sensitive to etoposide and cisplatin than
      parental cells. Furthermore, we found a tissue sample from a patient which showed
      increased expressions of CD56 and synaptophysin after development of resistance
      to erlotinib. CONCLUSION: NE differentiation can occur during acquisition of
      resistance to EGFR-TKI, leading to increased chemosensitivity.

PMID- 24101934
TI  - Plasma osteopontin is a useful diagnostic biomarker for advanced non-small cell
      lung cancer.
AB  - BACKGROUND: Osteopontin (OPN) and carbonic anhydrase IX (CAIX), which are
      expressed on the surface of tumor cells, are associated with hypoxia during tumor
      development and progression. However, the roles of these proteins in the plasma
      of patients with non-small cell lung cancer (NSCLC) are poorly understood.
      Herein, we hypothesized that plasma OPN and CAIX levels could be used as
      diagnostic and prognostic tumor markers in patients with NSCLC. METHODS: Fifty
      three patients with NSCLC and 50 healthy control subjects were enrolled. We
      selected controls without malignancy and matched them with NSCLC patient cases
      according to age and gender. Blood samples were collected at the time of
      diagnosis; the plasma levels of OPN and CAIX were measured by enzyme-linked
      immunosorbent assays. RESULTS: The plasma levels of OPN in the patients with
      NSCLC were significantly elevated as compared to those in the controls (p=0.016).
      However, there was no difference in the plasma level of CAIX between the NSCLC
      patients and controls. NSCLC patients with a distant metastasis had a remarkable
      increase in plasma OPN compared with patients without metastasis (p=0.026), but
      no such correlation was found for CAIX. There was no difference in overall
      survival rates according to the plasma level of OPN between the two groups (by
      Kaplan-Meier survival analysis). CONCLUSION: Plasma OPN levels were elevated in
      patients with NSCLC as compared with the controls, with greater elevation of OPN
      levels in the advanced stages of disease. Therefore, plasma OPN may have utility
      as a diagnostic, but not prognostic, biomarker of advanced NSCLC.

PMID- 24101935
TI  - Multiple cancers in a patient with systemic sclerosis and aggravated interstitial
      lung disease by chemotherapy.
AB  - Although the relationship between malignancy risk with systemic sclerosis (SSc)
      has been inconclusive, there are some previous studies for a positive
      correlation. Most patients with SSc have some degree of lung parenchymal
      involvement in the form of interstitial thickening and fibrosis. Interstitial
      lung disease is the most common pulmonary manifestation of SSc. Interstitial lung
      disease following chemotherapy (5-fluorouracil, leucovorin, and oxaliplatin
      [FOLFOX]) is an uncommon life-threatening complication and it is induced by
      oxaliplatin. We report a case of multiple cancers in a patient with SSc and
      aggravated interstitial lung disease by chemotherapy. 

PMID- 24101936
TI  - Isolated cervical lymph node sarcoidosis presenting in an asymptomatic neck mass:
      a case report.
AB  - Sarcoidosis, a systemic granulomatous disease of unknown etiology. The
      presentation of sarcoidal granuloma in neck nodes without typical manifestations
      of systemic sarcoidosis is difficult to diagnose. We describe the case of a 37
      year-old woman with an increasing mass on the right side of neck. The excisional
      biopsy from the neck mass showed noncaseating epithelioid cell granuloma of the
      lymph nodes. No evidence of mycobacterial or fungal infection was noted. Thoracic
      evaluations did not show enlargement of mediastinal lymph nodes or parenchymal
      abnormalities. Immunohistochemistry showed abundant expression of tumor necrosis
      factor-alpha in the granuloma. However, transforming growth factor-beta was not
      expressed, although interleukin-1beta was focally expressed. These
      immunohistochemical findings supported characterization of the granuloma and the
      diagnosis of sarcoidosis. Sarcoidosis can present with cervical lymph node
      enlargement without mediastinal or lung abnormality. Immunohistochemistry may
      support the diagnosis of sarcoidosis and characterization of granuloma. 

PMID- 24101937
TI  - Embolization of multiple systemic artery to pulmonary artery fistula with
      recurrent hemoptysis.
AB  - Herein, we report a case of multiple systemic arteries to pulmonary artery
      fistulas without any underlying causes, presenting recurrent hemoptysis.
      Transcatheter embolization was successfully performed several times on multiple
      systemic feeding arteries. Multiple systemic arteries to pulmonary fistulas can
      be a source of uncontrolled bleeding, and embolization may be a reasonable
      therapeutic option to control the bleeding. 

PMID- 24101938
TI  - Extremely increased serum carbohydrate antigen 19-9 levels caused by new or
      resistant infections to previous antibiotics in chronic lung diseases.
AB  - In this paper, we describe 72-year-old female patient without evidence of
      malignant disease presented with significantly elevated serum carbohydrate
      antigen (CA) 19-9 levels by respiratory infections. She was diagnosed with
      respiratory infections due to Mycobacterium avium complex and Pseudomonas
      aeruginosa. The serum CA 19-9 levels remarkably increased (1,453-5,300 U/mL;
      reference range, <37 U/mL) by respiratory infection and abruptly decreased (357
      534 U/mL) whenever infection was controlled by specific treatments. This case
      suggests that serum CA 19-9 levels may be used as a diagnostic marker to indicate
      new or resistant infections to previous antibiotics in chronic lung diseases
      without significant changes in chest X-ray findings. 

PMID- 24101939
TI  - The effects of sa-am acupuncture treatment on respiratory physiology parameters
      in amyotrophic lateral sclerosis patients: a pilot study.
AB  - Respiratory dysfunction and complications are the most common causes of death in
      amyotrophic lateral sclerosis. This is a pilot study to observe the changes in
      respiratory physiology parameters after Sa-am acupuncture treatment. Eighteen ALS
      patients received Sa-am acupuncture treatment twice a day for 5 days. The EtCO2,
      SpO2, RR, and pulse rate were measured for 15 min before and during treatment,
      using capnography and oximetry. Correlation of K-ALSFRS-R scores against measured
      parameters showed that patients who had high K-ALSFRS-R scores had greater
      changes in pulse rate after acupuncture stimulation; they also showed a decrease
      in EtCO2, RR, and pulse rate and an increase in SpO2. A comparison of the mean
      values of these different parameters before and after Sa-am acupuncture
      stimulation revealed statistically significant differences (P < 0.05) in SpO2 and
      pulse rate, but none in EtCO2 and RR. Sa-am acupuncture treatment on ALS patients
      seems to be more effective in the early stages of the disease. In light of
      increased SpO2 values, Sa-am acupuncture appears to have a greater effect on
      inspiration rather than on expiration. As a pilot study of acupuncture on ALS
      patients, this study could be used as a basis for future research. 

PMID- 24101940
TI  - Scopoletin inhibits rat aldose reductase activity and cataractogenesis in
      galactose-fed rats.
AB  - Cataracts are a major cause of human blindness. Aldose reductase (AR) is an
      important rate-limiting enzyme that contributes to cataract induction in diabetic
      patients. Scopoletin is the main bioactive constituent of flower buds from
      Magnolia fargesii and is known to inhibit AR activity. To assess scopoletin's
      ability to mitigate sugar cataract formation in vivo, we studied its effects in a
      rat model of dietary galactose-induced sugar cataracts. Galactose-fed rats were
      orally dosed with scopoletin (10 or 50 mg/kg body weight) once a day for 2 weeks.
      Administering scopoletin delayed the progression of the cataracts that were
      induced by dietary galactose. Scopoletin also prevented galactose-induced changes
      in lens morphology, such as lens fiber swelling and membrane rupture.
      Scopoletin's protective effect against sugar cataracts was mediated by inhibiting
      both AR activity and oxidative stress. These results suggest that scopoletin is a
      useful treatment for sugar cataracts. 

PMID- 24101941
TI  - Use of propolis hydroalcoholic extract to treat colitis experimentally induced in
      rats by 2,4,6-trinitrobenzenesulfonic Acid.
AB  - This study focused on the therapeutic effect of a propolis SLNC 106 (PI) extract
      on experimental colitis. Wistar adult rats received 0.8 mL rectal dose of one of
      the following solutions: saline (group S), 20 mg TNBS in 50% ethanol (group
      TNBS), 20 mg TNBS in 50% ethanol and propolis extract in saline (group TNBS-P),
      propolis extract in saline (group SP), and 20 mg TNBS in 50% ethanol and 50 mg/kg
      mesalazine (group TNBS-M). The animals were euthanized 7 or 14 days after the
      colitis induction. Samples of the distal colon were harvested for the analysis of
      myeloperoxidase (MPO) enzyme activity and for morphometric analysis in paraffin
      embedded histological sections with hematoxylin-eosin or histochemical staining.
      The animals treated with TNBS exhibited the typical clinical signs of colitis.
      Increased MPO activity confirmed the presence of inflammation. TNBS induced the
      development of megacolon, ulceration, transmural inflammatory infiltrate, and
      thickened bowel walls. Treatment with propolis moderately reduced the
      inflammatory response, decreased the number of cysts and abscesses, inhibited
      epithelial proliferation, and increased the number of goblet cells. The anti
      inflammatory activity of the propolis SLNC 106 extract was confirmed by the
      reductions in both the inflammatory infiltrate and the number of cysts and
      abscesses in the colon mucosa. 

PMID- 24101942
TI  - Contributory role of viral infection in congenital tumour development.
AB  - Congenital tumours are a group of distinct infrequent disorders whose exact
      aetiologies have not clearly been understood so far. Viral infection seems to be
      one of the key factors involved in the carcinogenesis of certain tumours. This
      study was performed to assess whether viral DNAs are present in the congenital
      tumours or not. Nucleic acid from 31 congenital tumours was extracted. Detection
      of Epstein-Barr virus, Cytomegalovirus (CMV), adenovirus, Herpes simplex virus 1
      (HSV1) and 2, Human herpes virus 6 (HHV6), and BK virus was performed using
      polymerase chain reaction. Viral nucleic acid was detected in eight subjects
      (25.8%), mostly adenovirus, CMV, and HHV6. Despite their low frequencies, a
      possible role could be identified for viral infections in tumour development or
      progression. 

PMID- 24101943
TI  - Robotics in uro-oncologic surgery.
AB  - In urology, the main use for the robotic technique has been in radical
      prostatectomy for prostate cancer. Robotic surgery for other organs, such as the
      kidneys and bladder, has been less explored. However, partial nephrectomy or
      radical nephroureterectomy can be difficult for inexperienced laparoscopic
      surgeons. The advent of the da Vinci robot, with multijointed endowristed
      instruments and stereoscopic vision, decreases the technical difficulty of
      intracorporeal suturing and improves the reconstructive steps. The objective of
      this article is to offer an overview of all robotic procedures recently developed
      in the field of urology. We evaluate the feasibility of these procedures and
      their potential advantages and disadvantages. We also describe perioperative,
      postoperative, and oncologic outcomes of robot-assisted surgery as well as
      perform a comparison with open and laparoscopic techniques. Comparative data and
      an adequate follow-up are needed to demonstrate equivalent oncologic outcomes in
      comparison with traditional open or laparoscopic procedures. 

PMID- 24101944
TI  - Robotic prostatectomy: an update on functional and oncologic outcomes.
AB  - Since the first procedure performed in 2000, robotic-assisted radical
      prostatectomy (RARP) has been rapidly gaining increasing acceptance from both
      urologists and patients. Today, RARP is the dominant treatment option for
      localised prostate cancer (PCa) in the United States, despite the absence of any
      prospective randomised trial comparing RARP with other procedures. Robotic
      systems have been introduced in an attempt to reduce the difficulty involved in
      performing complex laparoscopic procedures and the related steep learning curve.
      The recognised advantages of this kind of minimally invasive surgery are three
      dimensional (3D) vision, ten-fold magnification, Endowrist technology with seven
      degrees of freedom, and tremor filtration. In this article, we examine this
      technique and report its functional (in terms of urinary continence and potency)
      and oncologic results. We also evaluate the potential advantages of RARP in
      comparison with open and laparoscopic procedures. 

PMID- 24101945
TI  - Robotic bilateral inguinal lymphadenectomy in penile cancer, development of a
      technique without robot repositioning: a case report.
AB  - INTRODUCTION: Inguinal lymphadenectomy is the treatment of choice for patients
      with penile cancer and inguinal lymph node metastases. We describe the
      performance of the robotic bilateral inguinal lymphadenectomy technique without
      repositioning the robot in a patient with penile carcinoma and high risk for
      nodal metastases and no palpable lymph nodes. MATERIALS AND METHODS: A 64-year
      old male patient was diagnosed with penile cancer (TNM: T3 N 0 M 0) and underwent
      a total penectomy with perineal urethrostomy. We performed a robotic bilateral
      inguinal lymphadenectomy four weeks after the penectomy. RESULTS: The entire
      procedure was performed with the robot-assisted technique. The operative time,
      median estimated blood loss, and hospital stay was 360 min, 100 ml (50 ml in the
      right side and 150 ml in the left side), and three days, respectively. Metastatic
      nodes were present in both inguinal regions, with a yield of 19 lymph nodes on
      the right and 14 on the left. The patient presented with a left-side lymphocele
      that was drained at follow-up. No other complications were reported. CONCLUSION:
      Robotic bilateral inguinal lymphadenectomy secondary to penile cancer is
      feasible, safe, and provides a good performance. Prospective studies are required
      to include a larger number of patients and long-term monitoring to assess the
      results of this procedure in comparison with open and laparoscopic techniques.

PMID- 24101947
TI  - Treatment of osteoporosis in men with bisphosphonates: rationale and latest
      evidence.
AB  - Osteoporosis in men contributes to significant morbidity and mortality. Hip
      fractures in men are associated with greater mortality compared with women, with
      a mortality rate of up to 37.5% within a year following the fracture. Its timely
      diagnosis and treatment are therefore essential. However, despite one-third of
      all hip fractures worldwide occurring in men, osteoporosis in men remains an
      immensely under-recognized and undertreated public health problem.
      Bisphosphonates are well studied first-line treatments for postmenopausal women
      with osteoporosis and have been shown to reduce fragility fractures at all
      clinically important sites (vertebral, nonvertebral, hip and wrist). However, the
      majority of studies of oral or intravenous bisphosphonate therapy in men with
      osteoporosis report effects on surrogate markers, including bone mineral density
      (BMD) and biochemical bone turnover markers, rather than on fragility fractures.
      Oral or intravenous bisphosphonate therapy increases spinal, total hip and
      femoral neck BMD compared with placebo in men with osteoporosis. Both bone
      resorption and bone formation markers are decreased following bisphosphonate
      therapy, with the onset of the decrease in bone formation markers being delayed.
      In a study of intravenous zoledronic acid given to older men and women following
      a hip fracture, any clinical vertebral and nonvertebral fractures were all
      reduced compared with placebo infusions. In addition, mortality was reduced in
      patients who received zoledronic acid. Recent studies in men with osteoporosis
      have increasingly reported reductions in incident vertebral fractures with oral
      or intravenous bisphosphonate therapy, although all studies have been
      underpowered to detect effects on nonvertebral and hip fracture outcomes.
      Bisphosphonates have a role as monotherapy, as consolidative therapy after a
      course of teriparatide therapy, or in combination with testosterone replacement
      in men with hypogonadism and osteoporosis. Bisphosphonate therapy is validated
      and important in the treatment of osteoporosis in men. 

PMID- 24101946
TI  - The role of the robotic technique in minimally invasive surgery in rectal cancer.
AB  - Laparoscopic rectal surgery is feasible, oncologically safe, and offers better
      short-term outcomes than traditional open procedures in terms of pain control,
      recovery of bowel function, length of hospital stay, and time until return to
      working activity. Nevertheless, laparoscopic techniques are not widely used in
      rectal surgery, mainly because they require a prolonged and demanding learning
      curve that is available only in high-volume and rectal cancer surgery centres
      experienced in minimally invasive surgery. Robotic surgery is a new technology
      that enables the surgeon to perform minimally invasive operations with better
      vision and more intuitive and precise control of the operating instruments,
      promising to overcome some of the technical difficulties associated with standard
      laparoscopy. The aim of this review is to summarise the current data on clinical
      and oncological outcomes of minimally invasive surgery in rectal cancer, focusing
      on robotic surgery, and providing original data from the authors' centre. 

PMID- 24101948
TI  - Strontium ranelate in the treatment of knee osteoarthritis: new insights and
      emerging clinical evidence.
AB  - Osteoarthritis is a primary cause of disability and functional incapacity.
      Pharmacological treatment is currently limited to symptomatic management, and in
      advanced stages, surgery remains the only solution. The therapeutic armamentarium
      for osteoarthritis remains poor in treatments with an effect on joint structure,
      that is, disease-modifying osteoarthritis drugs (DMOADs). Glucosamine sulfate and
      chondroitin sulfate are the only medications for which some conclusive evidence
      for a disease-modifying effect is available. Strontium ranelate is currently
      indicated for the prevention of fracture in severe osteoporosis. Its efficacy and
      safety as a DMOAD in knee osteoarthritis has recently been explored in the SEKOIA
      trial, a 3-year randomized, double-blind, placebo-controlled trial. Outpatients
      with knee osteoarthritis, Kellgren and Lawrence grade 2 or 3, and joint space
      width (JSW) of 2.5-5 mm received strontium ranelate 1 g/day (n = 558) or 2 g/day
      (n = 566), or placebo (n = 559). This sizable population was aged 62.9 years and
      had a JSW of 3.50 +/- 0.84 mm. Treatment with strontium ranelate led to
      significantly less progression of knee osteoarthritis: estimates for annual
      difference in joint space narrowing versus placebo were 0.14 mm [95% confidence
      interval (CI) 0.05-0.23 mm; p < 0.001] for 1 g/day and 0.10 mm (95% CI 0.02-0.19
      mm; p = 0.018) for 2 g/day, with no difference between strontium ranelate groups.
      Radiological progression was less frequent with strontium ranelate (22% with 1
      g/day and 26% with 2 g/day versus 33% with placebo, both p < 0.05), as was
      radioclinical progression (8% and 7% versus 12%, both p < 0.05). Symptoms also
      improved with strontium ranelate 2 g/day only in terms of total WOMAC (Western
      Ontario and McMaster Universities Osteoarthritis Index) score (p = 0.045), and
      its components for pain (p = 0.028) and physical function (p = 0.099). Responder
      analyses using a range of criteria for symptoms indicated that the effect of
      strontium ranelate 2 g/day on pain and physical function was clinically
      meaningful. Strontium ranelate was well tolerated. The observation of both
      structure and symptom modification with strontium ranelate 2 g/day makes SEKOIA a
      milestone in osteoarthritis research and treatment. 

PMID- 24101949
TI  - Ustekinumab in the treatment of psoriatic arthritis: latest findings and clinical
      potential.
AB  - Ustekinumab (UST) is a fully human immunoglobulin G1kappa (IgG1kappa) monoclonal
      antibody against common sub-unit p40 of interleukin-12 (IL-12) and interleukin-23
      (IL-23). IL-12 and IL-23 are essential components of the Th1 and Th17
      inflammatory pathways, respectively, and are the key mediators of psoriasis.
      Psoriatic arthritis (PsA), an important systemic inflammatory disorder, has
      similar pathogenesis to psoriasis. Many of PsA patients do not respond to tumor
      necrosis factor (TNF) inhibitor therapy, highlighting the need for additional
      treatment modalities with distinct mechanisms of action. Also, many patients stop
      responding to these agents after a certain period of use. A significant number of
      patients have a recurrent course or a persistent disease process. To meet these
      challenges a new agent working on different inflammatory aspect of PsA is needed.
      UST has been demonstrated to be effective, safe on short-term use and convenient
      in the treatment of plaque psoriasis and PsA. Long-term safety is still a
      concern. Until recently, the exact role of UST in the management of PsA had not
      been very clear. This article reviews the mechanism of action, pharmacokinetics,
      efficacy, safety profile and the clinical potential of UST in patients with PsA.
      We also discuss the three major trials conducted to show the efficacy and safety
      of UST in PsA. 

PMID- 24101951
TI  - Application of positive end expiratory pressure during laparoscopic surgery.

PMID- 24101950
TI  - Therapeutic roles of heme oxygenase-1 in metabolic diseases: curcumin and
      resveratrol analogues as possible inducers of heme oxygenase-1.
AB  - Metabolic diseases, such as insulin resistance, type II diabetes, and obesity,
      are associated with a low-grade chronic inflammation (inflammatory stress),
      oxidative stress, and endoplasmic reticulum (ER) stress. Because the integration
      of these stresses is critical to the pathogenesis of metabolic diseases, agents
      and cellular molecules that can modulate these stress responses are emerging as
      potential targets for intervention and treatment of metabolic diseases. It has
      been recognized that heme oxygenase-1 (HO-1) plays an important role in cellular
      protection. Because HO-1 can reduce inflammatory stress, oxidative stress, and ER
      stress, in part by exerting antioxidant, anti-inflammatory, and antiapoptotic
      effects, HO-1 has been suggested to play important roles in pathogenesis of
      metabolic diseases. In the present review, we will explore our current
      understanding of the protective mechanisms of HO-1 in metabolic diseases and
      present some emerging therapeutic options for HO-1 expression in treating
      metabolic diseases, together with the therapeutic potential of curcumin and
      resveratrol analogues that have their ability to induce HO-1 expression. 

PMID- 24101953
TI  - Dexmedetomidine for sedation of patients undergoing elective surgery under
      regional anesthesia.
AB  - BACKGROUND: Dexmedetomidine may be useful as a sedative agent. However, it has
      been reported that dexmedetomidine decreases systemic blood pressure, heart rate,
      and cardiac output in a dose-dependent manner. The purpose of this study was to
      determine the appropriate dose of intravenously administered dexmedetomidine for
      sedation. METHODS: Forty-five American Society of Anesthesiologists physical
      status I-II patients under spinal anesthesia received dexmedetomidine 1 ug/kg
      intravenously as a loading dose. The patients were randomly allocated to one of
      three groups for maintenance dose: Group A (0.25 ug/kg/hr), Group B (0.50
      ug/kg/hr), and Group C (0.75 ug/kg/hr). The hemodynamic variables and the Ramsay
      Sedation Scale (RSS) score were recorded for all patients. The numbers of
      patients who developed hypotension, bradycardia, or inadequate sedation
      necessitating further drug treatment were also recorded. RESULTS: Systolic blood
      pressure, heart rate, and SpO2 were decreased, and RSS score was increased
      significantly at both 20 min and 40 min after injection of dexmedetomidine in the
      three study groups compared to baseline, without significant differences between
      the groups. The prevalence of hypotension, but not that of bradycardia or
      adjunctive midazolam administration, exhibited a positive correlation with the
      dose of dexmedetomidine. CONCLUSIONS: Intravenous injection of dexmedetomidine 1
      ug/kg followed by continuous administration at infusion rates of 0.25, 0.50, or
      0.75 ug/kg/hr produced adequate levels of sedation. However, there was a tendency
      for the incidence of hypotension to increase as the dose increased. To minimize
      the risk of hemodynamic instability, a dose of 0.25 ug/kg/hr may be the most
      appropriate for continuous administration of dexmedetomidine.

PMID- 24101952
TI  - Delirium in the intensive care unit.
AB  - Delirium is a serious complication that commonly occurs in critically ill
      patients in the intensive care unit (ICU). Delirium is frequently unrecognized or
      missed despite its high incidence and prevalence, and leads to poor clinical
      outcomes and an increased cost by increasing morbidity, mortality, and hospital
      and ICU length of stay. Although its pathophysiology is poorly understood,
      numerous risk factors for delirium have been suggested. To improve clinical
      outcomes, it is crucial to perform preventive measures against delirium, to
      detect delirium early using valid and reliable screening tools, and to treat the
      underlying causes or hazard symptoms of delirium in a timely manner. 

PMID- 24101954
TI  - General anesthesia versus monitored anesthetic care with dexmedetomidine for
      closed reduction of nasal bone fracture.
AB  - BACKGROUND: Reduction of nasal bone fracture can be performed under general or
      local anesthesia. The aim of this study was to compare general anesthesia (GA)
      and monitored anesthetic care (MAC) with dexmedetomidine based on intraoperative
      vital signs, comfort of patients, surgeons and nurses and the adverse effects
      after closed reduction of nasal bone fractures. METHODS: Sixty patients with
      American Society of Anesthesiologists physical status I or II were divided into a
      GA group (n = 30) or MAC group (n = 30). Standard monitorings were applied. In
      the GA group, general anesthesia was carried out with propofol-sevoflurane-N2O.
      In the MAC group, dexmedetomidine and local anesthetics were administered for
      sedation and analgesia. Intraoperative vital signs, postoperative pain scores by
      visual analog scale and postoperative nausea and vomiting (PONV) were compared
      between the groups. RESULTS: Intraoperatively, systolic blood pressures were
      significantly higher, and heart rates were lower in the MAC group compared to the
      GA group. There were no differences between the groups in the patient, nurse and
      surgeon's satisfaction, postoperative pain scores and incidence of PONV.
      CONCLUSIONS: MAC with dexmedetomidine resulted in comparable satisfaction in the
      patients, nurses and surgeons compared to general anesthesia. The incidence of
      postoperative adverse effects and severity of postoperative pain were also
      similar between the two groups. Therefore, both anesthetic techniques can be used
      during the reduction of nasal bone fractures based on a patient%s preference and
      medical condition.

PMID- 24101955
TI  - The comparison of feasibility and safety on fiberoptic guided intubation under
      conscious sedation with remifentanil and propofol.
AB  - BACKGROUND: Oropharyngeal manipulation is problematic when patients have a gag
      reflex. Sedation can suppress gag reflex, but can cause serious airway problems.
      We compared remifentanil (Group R) and propofol (Group P) in terms of cooperation
      and loss of gag reflex, while drugs were administered incrementally using target
      controlled infusion (TCI). METHODS: Fifty seven patients who required awake
      fiberoptic intubation were randomized to Group R or Group P. After measurement of
      baseline gag trigger point index (GTPI), TCI was set to effect-site concentration
      (Ce) of 1 ng/ml (Group R) or 1 ug/ml (Group P), then titrated by 0.5 increment
      until GTPI score reached 0. The incidence of drop-out and decreased cooperation,
      Ramsay sedation scale (RSS) and Ce at loss of GR, and complications were
      assessed. RESULTS: Seven patients were dropped out in Group P due to deep
      sedation and disobedient behavior, but none in Group R (P = 0.015). Gag reflex
      suppressed as RSS increased in both groups (P < 0.001), however, the incidence of
      elimination of gag reflex clustered at RSS 2 in Group R (P < 0.001), whereas it
      was evenly distributed in Group P (P = 0.20). The incidence of patients who were
      spontaneously roused (gag reflex elimination at RSS 1 and 2) were higher in Group
      R than in Group P (P = 0.002). CONCLUSIONS: Deep sedation and impaired
      cooperation were observed only in Group P and spontaneously roused patients were
      higher in Group R, suggesting that remifentanil is more suitable for cooperative
      elimination of GR.

PMID- 24101956
TI  - Pretreatment of magnesium sulphate improves intubating conditions of rapid
      sequence tracheal intubation using alfentanil, propofol, and rocuronium - a
      randomized trial.
AB  - BACKGROUND: We investigated the effects of a magnesium sulfate pretreatment on
      intubating conditions and cardiovascular responses during rapid sequence tracheal
      intubation (RSI) in this double-blind randomized study. METHODS: Adult patients
      (n = 154) were randomly allocated to a rocuronium-0.6, rocuronium-0.9, or
      magnesium group. The magnesium group was pretreated with 50 mg/kg MgSO4, and the
      other two groups received the same volume of isotonic saline. Anesthesia was
      induced with alfentanil, propofol, and either 0.6 mg/kg (rocuronium-0.6 and
      magnesium groups) or 0.9 mg/kg (rocuronium-0.9 group) rocuronium. An
      anesthesiologist, blinded to the group assignments, performed RSI and assessed
      the intubating conditions. Systolic arterial pressure (SAP) and heart rate (HR)
      were recorded before the magnesium sulfate or normal saline was administered,
      before anesthesia induction, before intubation, and every minute after intubation
      for 5 min. RESULTS: Airway features were similar among the three groups. The
      intubating conditions were improved significantly in the magnesium group (P <
      0.001) compared with the other two groups. Significant increases in SAP at 1 min
      after intubation were observed in the rocuronium-0.6 and -0.9 groups when
      compared with the magnesium group (P < 0.05). HR was comparable among the three
      groups (P > 0.05). No hypertensive episode occurred during the immediate post
      intubation period in the magnesium group (P = 0.001), and tachycardia occurred
      most frequently in the rocuronium-0.6 group (P < 0.05). CONCLUSIONS: MgSO4
      administered prior to RSI using alfentanil, propofol, and rocuronium may improve
      intubating conditions and prevent post-intubation hypertension.

PMID- 24101957
TI  - Perioperative risk factors for prolonged mechanical ventilation after liver
      transplantation due to acute liver failure.
AB  - BACKGROUND: Acute liver failure (ALF) is a rapidly progressing and fatal disease
      for which liver transplantation (LT) is the only treatment. Posttransplant
      mechanical ventilation tends to be more prolonged in patients with ALF than in
      other LT patients. The present study examined the clinical effects of prolonged
      posttransplant mechanical ventilation (PMV), and identified risk factors for PMV
      following LT for ALF. METHODS: We reviewed data of patients undergoing LT for ALF
      between January 2005 and June 2011. After grouping patients according to
      administration of PMV (>= 24 h), donor and recipient perioperative variables were
      compared between the groups with and without PMV. Potentially significant factors
      (P < 0.1) from the univariate intergroup comparison were entered into a
      multivariate logistic regression to establish a predictive model for PMV.
      RESULTS: Twenty-four (25.3%) of 95 patients with ALF who received PMV had a
      higher mortality rate (29.2% vs 11.3%, P = 0.038) and longer intensive care unit
      stay (12.9 +/- 10.4 vs 7.1 +/- 2.7 days, P = 0.012) than patients without PMV.
      The intergroup comparisons revealed worse preoperative hepatic conditions, more
      supportive therapy, and more intraoperative fluctuations in vital signs and less
      urine output in the with- compared with the without-PMV group. The multivariate
      analysis revealed that preoperative hepatic encephalopathy (>= grade III),
      intraoperative blood pressure fluctuation, and oliguria (< 0.5 ml/kg/h) were
      independent risk factors for PMV. CONCLUSIONS: PMV was associated with
      deleterious outcomes. Besides care for known risk factors including hepatic
      encephalopathy, meticulous attention to managing intraoperative hemodynamic
      circulatory status is required to avoid PMV and improve the posttransplant
      prognosis in ALF patients.

PMID- 24101958
TI  - Pulse pressure variation and stroke volume variation to predict fluid
      responsiveness in patients undergoing carotid endarterectomy.
AB  - BACKGROUND: During carotid endarterectomy (CEA), hemodynamic stability and
      adequate fluid management are crucial to prevent perioperative cerebral stroke,
      myocardial infarction and hyperperfusion syndrome. Both pulse pressure variation
      (PPV) and stroke volume variation (SVV), dynamic preload indices derived from the
      arterial waveform, are increasingly advocated as predictors of fluid
      responsiveness in mechanically ventilated patients. The aim of this study was to
      evaluate the accuracy of PPV and SVV for predicting fluid responsiveness in
      patients undergoing CEA. METHODS: Twenty seven patients undergoing CEA were
      enrolled in this study. PPV, SVV and cardiac output (CO) were measured before and
      after fluid loading of 500 ml of hydroxyethyl starch solution. Fluid
      responsiveness was defined as an increase in CO >= 15%. The ability of PPV and
      SVV to predict fluid responsiveness was assessed using receiver operating
      characteristic (ROC) analysis. RESULTS: Both PPV and SVV measured before fluid
      loading are associated with changes in CO caused by fluid expansion. The ROC
      analysis showed that PPV and SVV predicted response to volume loading (area under
      the ROC curve = 0.854 and 0.841, respectively, P < 0.05). A PPV >= 9.5%
      identified responders (Rs) with a sensitivity of 71.4% and a specificity of
      90.9%, and a SVV >= 7.5% identified Rs with a sensitivity of 92.9% and a
      specificity of 63.6%. CONCLUSIONS: Both PPV and SVV values before volume loading
      are associated with increased CO in response to volume expansion. Therefore, PPV
      and SVV are useful predictors of fluid responsiveness in patients undergoing CEA.

PMID- 24101959
TI  - Optimal positive end-expiratory pressure during robot-assisted laparoscopic
      radical prostatectomy.
AB  - BACKGROUND: Increased intra-abdominal pressure during laparoscopic surgery causes
      cephalad displacement of the diaphragm, resulting in the formation of
      atelectasis, which can be overcome by positive end-expiratory pressure (PEEP).
      The aim of this prospective study was to investigate the level of optimal PEEP to
      maintain adequate arterial oxygenation and hemodynamics during robot-assisted
      laparoscopic radical prostatectomy (RLRP). METHODS: One hundred patients
      undergoing RLRP were randomly allocated to one of five groups (n = 20) (0, 3, 5,
      7 and 10 cmH2O of PEEP). Hemodynamic variables and respiratory parameters were
      measured at baseline with the patient in the supine position; at 30 min, 1, 2, 3
      and 4 h during CO2 insufflation with the patient in the post-Trendelenburg
      position; and after deflation in the supine position with increasing PEEP.
      RESULTS: The PaO2 levels and alveolar-arterial difference in oxygen tension
      (AaDO2) were improved in patients with PEEPs compared with patients in whom PEEP
      was not used. The application of PEEP (10 cmH2O) resulted in higher PaO2 levels
      compared to those with lower PEEP levels, but excessive peak airway pressure
      (PAP) was sometimes observed. The application of a PEEP of 7 cmH2O resulted in
      similar PaO2 levels without causing excessive PAP. There was a significant
      difference in central venous pressure between the groups, but there were no
      significant differences in heart rate, mean arterial pressure or minute
      ventilation between the groups. CONCLUSIONS: A PEEP of 7 cmH2O is associated with
      the greater improvement of PaO2 and AaDO2 without causing excessive PAP during
      RLRP.

PMID- 24101961
TI  - Use of the i-gelTM supraglottic airway device in a patient with subglottic
      stenosis -a case report-.
AB  - The airway management of patients with subglottic stenosis poses many challenges
      for the anesthesiologists. Many anesthesiologists use a narrow endotracheal tube
      for airway control. This, however, can lead to complications such as tracheal
      mucosal trauma, tracheal perforation or bleeding. The ASA difficult airway
      algorithm recommends the use of supraglottic airway devices in a failed
      intubation/ventilation scenario. In this report, we present a case of failed
      intubation in a patient with subglottic stenosis successfully managed during an i
      gelTM supraglottic airway device. The device provided a good seal, and allowed
      for controlled mechanical ventilation with acceptable peak pressures while the
      patient was in the beach-chair position. 

PMID- 24101960
TI  - Aspiration pneumonia caused by fentanyl-induced cough -a case report-.
AB  - Although fentanyl-induced cough is generally transient and benign, it can give
      rise to serious problems in patients to whom increasing intracranial, intraocular
      or intraabdominal pressures may create dangerous situations. This case
      demonstrates aspiration pneumonia as a complication, exhibiting severe cough
      induced by intravenous injection of fentanyl. 

PMID- 24101962
TI  - Intractable metabolic acidosis in a child with propionic acidemia undergoing
      liver transplantation -a case report-.
AB  - Propionic acidemia (PA) is a rare autosomal recessive disorder of metabolism
      caused by deficient activity of the mitochondrial enzyme propionyl-CoA
      carboxylase. The clinical manifestations are metabolic acidosis, poor feeding,
      lethargy, vomiting, osteoporosis, neurological dysfunction, pancytopenia,
      developmental retardation and cardiomyopathy. Liver transplantation has recently
      been considered as one of the treatment options for patients with PA. This case
      report describes several anesthetic considerations for patients with PA
      undergoing liver transplantation. Understanding the patient's status and avoiding
      events that may precipitate metabolic acidosis are important for anesthetic
      management of patients with PA. In conclusion, anesthesia should be focused on
      minimizing the severity of metabolic acidosis with following considerations: (1)
      maintaining optimal tissue perfusion by avoiding hypotension, (2) preventing
      hypoglycemia, and (3) providing bicarbonate to compensate for the acidosis. 

PMID- 24101963
TI  - Sudden severe hyperammonemia and status epilepticus -a case report-.
AB  - There are various causes to a low level of consciousness in patients in the
      intensive care unit. Neurological injury, infection, and metabolic disarray are
      considered as some of the causes. A 39 year-old female patient was transferred to
      our hospital with septic shock due to ascending colon perforation. The patient
      had previously received ovarian cancer surgery and a cycle of chemotherapy at
      another hospital. Emergent operation for colon perforation was successful. After
      the operation, she was treated in the intensive care unit for infectious and
      pulmonary complications. She suddenly showed deterioration in her level of
      consciousness and had a generalized seizure. At the time of her seizure, she had
      severe hyperammonemia. Brain CT showed severe cerebral edema that was absent in
      the CT scan taken 2 days before. Continuous renal replacement therapy was
      conducted but was ineffective in lowering the level of serum ammonia and the
      patient subsequently died. 

PMID- 24101964
TI  - Asymptomatic pneumomediastinum resulting from air in the epidural space -a case
      report-.
AB  - There are no reports regarding pneumomediastinum caused by thoracic epidural
      block complications. We believe that it is possible to experience an occurrence
      of pneumomediastinum caused by air in the epidural space after performing a
      thoracic epidural block using the loss of resistance (LOR) technique with air. We
      report a witnessed case where pneumomediastinum appeared after a thoracic
      epidural block. Pneumorrrhachis, paravertebral muscle emphysema, and
      pneumomediastinum were diagnosed by Positron Emission Tomography-Computed
      Tomography. Although extremely rare, pneumomediastinum can be caused by an
      epidural block using LOR technique with air. In order to avoid the above danger,
      the use of saline or very minimal amount of air is required during a careful LOR
      technique. 

PMID- 24101965
TI  - Occurrence of a spinal intradural arachnoid cyst after epiduroscopic neural
      decompression.

PMID- 24101966
TI  - Rescue of hemodynamic compromise in superior vena cava syndrome with
      transesophageal echocardiography.

PMID- 24101967
TI  - Bradycardia during laparoscopic surgery due to high flow rate of CO2
      insufflation.

PMID- 24101968
TI  - The usefulness of ankle-brachial index as a screening test on peripheral artery
      occlusive disease in patients with low back and leg pain.

PMID- 24101969
TI  - Intrusive luxation of tooth due to bite block after oral endotracheal intubation.

PMID- 24101971
TI  - A Concise Enantioselective Synthesis and Cytotoxic Evaluation of the Anticancer
      Rotenoid Deguelin Enabled by a Tandem Knoevenagel/Conjugate
      Addition/Decarboxylation Sequence.
AB  - (-)-Deguelin is a rotenoid natural product that possesses significant potential
      as a chemopreventive and chemotherapeutic agent. While several racemic syntheses
      of deguelin have been reported, a formal evaluation of the anticancer activity of
      both the natural and unnatural enantiomers remains lacking. We describe herein
      the successful application of a flexible and selective thiourea-catalyzed
      cyclization strategy toward the enantioselective total synthesis of deguelin,
      which allows access to either stereoisomer for biological studies. The synthesis
      was completed in six steps (longest linear) with no protecting groups. The
      evaluation of both enantiomers of the natural product demonstrated potent
      inhibition of several cancer cell lines by these compounds, but interestingly
      showed that the unnatural (+)-deguelin preferentially inhibited the growth of MCF
      7 breast cancer and HepG2 liver carcinoma cells when compared to the natural
      product.

PMID- 24101972
TI  - Do elevations in temperature, CO2, and nutrient availability modify belowground
      carbon gain and root morphology in artificially defoliated silver birch
      seedlings?
AB  - Climate warming increases the risk of insect defoliation in boreal forests.
      Losses in photosynthetically active surfaces cause reduction in net primary
      productivity and often compromise carbon reserves of trees. The concurrent
      effects of climate change and removal of foliage on root growth responses and
      carbohydrate dynamics are poorly understood, especially in tree seedlings. We
      investigated if exposures to different combinations of elevated temperature, CO2,
      and nutrient availability modify belowground carbon gain and root morphology in
      artificially defoliated 1-year-old silver birches (Betula pendula). We quantified
      nonstructural carbohydrates (insoluble starch as a storage compound; soluble
      sucrose, fructose, and glucose) singly and in combination in fine roots of plants
      under winter dormancy. Also the total mass, fine root proportion, water content,
      and length of roots were defined. We hypothesized that the measured properties
      are lower in defoliated birch seedlings that grow with ample resources than with
      scarce resources. On average, fertilization markedly decreased both the
      proportion and the carbohydrate concentrations of fine roots in all seedlings,
      whereas the effect of fertilization on root water content and dry mass was the
      opposite. However, defoliation mitigated the effect of fertilization on the root
      water content, as well as on the proportion of fine roots and their carbohydrate
      concentrations by reversing the outcomes. Elevation in temperature decreased and
      elevation in CO2 increased the absolute contents of total nonstructural
      carbohydrates, whereas fertilization alleviated both these effects. Also the root
      length and mass increased by CO2 elevation. This confirms that surplus carbon in
      birch tissues is used as a substrate for storage compounds and for cell wall
      synthesis. To conclude, our results indicate that some, but not all elements of
      climate change alter belowground carbon gain and root morphology in defoliated
      silver birch seedlings. 

PMID- 24101973
TI  - How landscape scale changes affect ecological processes in conservation areas:
      external factors influence land use by zebra (Equus burchelli) in the Okavango
      Delta.
AB  - Most large-bodied wildlife populations in sub-Saharan Africa only survive in
      conservation areas, but are continuing to decline because external changes
      influence ecological processes within reserves, leading to a lack of
      functionality. However, failure to understand how landscape scale changes
      influence ecological processes limits our ability to manage protected areas. We
      used GPS movement data to calculate dry season home ranges for 14 zebra mares in
      the Okavango Delta and investigated the effects of a range of landscape
      characteristics (number of habitat patches, mean patch shape, mean index of
      juxtaposition, and interspersion) on home range size. Resource utilization
      functions (RUF) were calculated to investigate how specific landscape
      characteristics affected space use. Space use by all zebra was clustered. In the
      wetter (Central) parts of the Delta home range size was negatively correlated
      with the density of habitat patches, more complex patch shapes, low juxtaposition
      of habitats and an increased availability of floodplain and grassland habitats.
      In the drier (Peripheral) parts of the Delta, higher use by zebra was also
      associated with a greater availability of floodplain and grassland habitats, but
      a lower density of patches and simpler patch shapes. The most important landscape
      characteristic was not consistent between zebra within the same area of the
      Delta, suggesting that no single foraging strategy is substantially superior to
      others, and so animals using different foraging strategies may all thrive. The
      distribution and complexity of habitat patches are crucial in determining space
      use by zebra. The extent and duration of seasonal flooding is the principal
      process affecting habitat patch characteristics in the Okavango Delta,
      particularly the availability of floodplains, which are the habitat at greatest
      risk from climate change and anthropogenic disturbance to the Okavango's
      catchment basin. Understanding how the factors that determine habitat complexity
      may change in the future is critical to the conservation of large mammal
      populations. Our study shows the importance of maintaining flood levels in the
      Okavango Delta and how the loss of seasonal floodplains will be compounded by
      changes in habitat configuration, forcing zebra to change their relative space
      use and enlarge home ranges, leading to increased competition for key resources
      and population declines. 

PMID- 24101974
TI  - Genetic attributes of midwife toad (Alytes obstetricans) populations do not
      correlate with degree of species decline.
AB  - Genetic diversity is crucial for long-term population persistence. Population
      loss and subsequent reduction in migration rate among the most important
      processes that are expected to lead to a reduction in genetic diversity and an
      increase in genetic differentiation. While the theory behind this is well
      developed, empirical evidence from wild populations is inconsistent. Using
      microsatellite markers, we compared the genetic structure of populations of an
      amphibian species, the midwife toad (Alytes obstetricans), in four Swiss regions
      where the species has suffered variable levels of subpopulation extirpation. We
      also quantified the effects of several geographic factors on genetic structure
      and used a model selection approach to ascertain which of the variables were
      important for explaining genetic variation. Although subpopulation pairwise F ST
      values were highly significant even over small geographic scales, neither any of
      the geographic variables nor loss of subpopulations were important factors for
      predicting spatial genetic structure. The absence of a signature of subpopulation
      loss on genetic differentiation may suggest that midwife toad subpopulations
      function as relatively independent units. 

PMID- 24101975
TI  - Flexible mate choice when mates are rare and time is short.
AB  - Female mate choice is much more dynamic than we once thought. Mating decisions
      depend on both intrinsic and extrinsic factors, and these two may interact with
      one another. In this study, we investigate how responses to the social mating
      environment (extrinsic) change as individuals age (intrinsic). We first conducted
      a field survey to examine the extent of natural variation in mate availability in
      a population of threespine sticklebacks. We then manipulated the sex ratio in the
      laboratory to determine the impact of variation in mate availability on sexual
      signaling, competition, and mating decisions that are made throughout life. Field
      surveys revealed within season heterogeneity in mate availability across breeding
      sites, providing evidence for the variation necessary for the evolution of
      plastic preferences. In our laboratory study, males from both female-biased and
      male-biased treatments invested most in sexual signaling late in life, although
      they competed most early in life. Females became more responsive to courtship
      over time, and those experiencing female-biased, but not male-biased sex ratios,
      relaxed their mating decisions late in life. Our results suggest that social
      experience and age interact to affect sexual signaling and female mating
      decisions. Flexible behavior could mediate the potentially negative effects of
      environmental change on population viability, allowing reproductive success even
      when preferred mates are rare. 

PMID- 24101976
TI  - Community patterns of the small riverine benthos within and between two
      contrasting glacier catchments.
AB  - Ongoing glacial retreat is expected to lead to numerous changes in glacier-fed
      rivers. This study documents the development of community composition of the
      hitherto widely neglected micro- and meiobenthos (MMB: bacteria, fungi, algae,
      protists, and meiofauna) in glacier rivers in response to the distinct habitat
      conditions driven by different stages of (de)glacierization. Our model is based
      on the glacier catchments of the Moll River (MC) and Kleinelendbach stream (KC),
      in the Austrian Alps, with 60% and 25% glacierization and glacier retreats of 403
      and 26 m, respectively, since 1998. Analyses of overall catchment diversity and
      resemblance patterns showed that neither intense glacierization nor rapid
      deglacierization were predominant MMB determinants. This was ascribed to the
      specific environmental conditions at the MC, where the rapidly retreating
      Pasterze glacier has formed a harsh unstable proglacial, but also a benign
      floodplain area, with the former suppressing and the latter supporting the
      structural development of the MMB. Comparisons of similarly aged riverine
      habitats of the MC proglacial and the KC main channel further evidenced
      developmental suppression of the MMB (64 taxa) by the rapidly retreating MC
      glacier, unlike the moderate glacial retreat in the KC (130 taxa). Habitat
      conditions interacting with melt periods explained the differences in MMB
      resemblance patterns, which themselves differentially reflected the
      spatiotemporal habitat settings imposed by the different glacier activities. The
      varying glacial influences were represented by a glaciality index (GIm) based on
      water temperature, electrical conductivity, and stream bed stability. The
      taxonomic richness of nematodes, rotifers, algae, and diatoms was distinctly
      related to this index, as were most MMB abundances. However, the strongest
      relationships to the GIm were those of nematode abundances and maturity. Our
      observations highlight the intense response of the MMB to ongoing glacier retreat
      and the utility of a simple index to reveal such patterns. 

PMID- 24101977
TI  - Understanding the contribution of habitats and regional variation to long-term
      population trends in tricolored blackbirds.
AB  - Population trends represent a minimum amount of information required to assess
      the conservation status of a species. However, understanding and detecting trends
      can be complicated by variation among habitats and regions, and by dispersal
      connecting habitats through source-sink dynamics. We analyzed trends in breeding
      populations between habitats and regions to better understand the overall
      dynamics of a species' decline. Specifically, we analyzed historical trends in
      breeding populations of tricolored blackbirds (Agelaius tricolor) using breeding
      records from 1907 to 2009. The species breeds itinerantly and ephemerally uses
      multiple habitat types and breeding areas, which make interpretation of trends
      complex. We found overall abundance declines of 63% between 1935 and 1975. Since
      1980 overall declines became nonsignificant and obscure despite large amounts of
      data from 1980 to 2009. Temporal trends differed between breeding habitat types
      and were associated with regional differences in population declines. A new
      habitat, triticale crops (a wheat-rye hybrid grain) produced colonies 40* larger,
      on average, than other breeding habitats, and contributed to a change in regional
      distribution since it primarily occurred in a single region. The mechanism for
      such an effect is not clear, but could represent the local availability of
      foodstuffs in the landscape rather than something specific to triticale crops.
      While variation in trends among habitats clearly occurred, they could not easily
      be ascribed to source-sink dynamics, ecological traps, habitat selection or other
      detailed ecological mechanisms. Nonetheless, such exchanges provide valuable
      information to guide management of dynamic systems. 

PMID- 24101978
TI  - Heat stress but not inbreeding affects offensive sperm competitiveness in
      Callosobruchus maculatus.
AB  - Environmental and genetic stress have well-known detrimental effects on ejaculate
      quality, but their concomitant effect on male fitness remains poorly understood.
      We used competitive fertilization assays to expose the effects of stress on
      offensive sperm competitive ability in the beetle Callosobruchus maculatus, a
      species where ejaculates make up more than 5% of male body mass. To examine the
      effects of environmental and genetic stress, males derived from outcrosses or sib
      matings were heat shocked at 50 degrees C for 50 min during the pupal stage,
      while their siblings were maintained at a standard rearing temperature of 28
      degrees C. Heat-shocked males achieved only half the offensive paternity success
      of their siblings. While this population exhibited inbreeding depression in body
      size, sperm competitiveness was unaffected by inbreeding, nor did the effect of
      heat shock stress on sperm competitiveness depend on inbreeding status. In
      contrast, pupal emergence success was increased by 34% among heat-stressed
      individuals, regardless of their inbreeding status. Heat-shocked males' ejaculate
      size was 19% reduced, but they exhibited 25% increased mating duration in single
      mating trials. Our results highlight both the importance of stress in
      postcopulatory sexual selection, and the variability among stressors in affecting
      male fitness. 

PMID- 24101979
TI  - Landscape heterogeneity drives intra-population niche variation and reproduction
      in an arctic top predator.
AB  - While intra-population variability in resource use is ubiquitous, little is known
      of how this measure of niche diversity varies in space and its role in population
      dynamics. Here we examined how heterogeneous breeding environments can structure
      intra-population niche variation in both resource use and reproductive output. We
      investigated intra-population niche variation in the Arctic tundra ecosystem,
      studying peregrine falcon (Falco peregrinus tundrius, White) breeding within a
      terrestrial-marine gradient near Rankin Inlet, Nunavut, Canada. Using stable
      isotope analysis, we found that intra-population niches varied at the individual
      level; we examined within-nest and among-nest variation, though only the latter
      varied along the terrestrial-marine gradient (i.e., increased among-nest
      variability among birds nesting within the marine environment, indicating higher
      degree of specialization). Terrestrial prey species (small herbivores and
      insectivores) were consumed by virtually all falcons. Falcons nesting within the
      marine environment made use of marine prey (sea birds), but depended heavily on
      terrestrial prey (up to 90% of the diet). Using 28-years of peregrine falcon
      nesting data, we found a positive relationship between the proportion of
      terrestrial habitat surrounding nest sites and annual nestling production, but no
      relationship with the likelihood of successfully rearing at least one nestling
      reaching 25 days old. Annually, successful inland breeders raised 0.47 more young
      on average compared to offshore breeders, which yields potential fitness
      consequences for this long-living species. The analyses of niche and reproductive
      success suggest a potential breeding cost for accessing distant terrestrial prey,
      perhaps due to additional traveling costs, for those individuals with marine nest
      site locations. Our study indicates how landscape heterogeneity can generate
      proximate (niche variation) and ultimate (reproduction) consequences on a
      population of generalist predator. We also show that within-individual and among
      individual variation are not mutually exclusive, but can simultaneously arise and
      structure intra-population niche variation. 

PMID- 24101980
TI  - The influence of landscape matrix on isolated patch use by wide-ranging animals:
      conservation lessons for woodland caribou.
AB  - For conservation purposes, it is important to design studies that explicitly
      quantify responses of focal species to different land management scenarios. Here,
      we propose an approach that combines the influence of landscape matrices with the
      intrinsic attributes of remaining habitat patches on the space use behavior of
      woodland caribou (Rangifer tarandus caribou), a threatened subspecies of
      Rangifer. We sought to link characteristics of forest remnants and their
      surrounding environment to caribou use (i.e., occurrence and intensity). We
      tracked 51 females using GPS telemetry north of the Saguenay River (Quebec,
      Canada) between 2004 and 2010 and documented their use of mature forest remnants
      ranging between 30 and ~170 000 ha in a highly managed landscape. Habitat
      proportion and anthropogenic feature density within incremental buffer zones
      (from 100 to 7500 m), together with intrinsic residual forest patch
      characteristics, were linked to caribou GPS location occurrence and density to
      establish the range of influence of the surrounding matrix. We found that patch
      size and composition influence caribou occurrence and intensity of use within a
      patch. Patch size had to reach approximately 270 km(2) to attain 75% probability
      of use by caribou. We found that small patches (<100 km(2)) induced concentration
      of caribou activities that were shown to make them more vulnerable to predation
      and to act as ecological traps. Woodland caribou clearly need large residual
      forest patches, embedded in a relatively undisturbed matrix, to achieve low
      densities as an antipredator strategy. Our patch-based methodological approach,
      using GPS telemetry data, offers a new perspective of space use behavior of wide
      ranging species inhabiting fragmented landscapes and allows us to highlight the
      impacts of large scale management. Furthermore, our study provides insights that
      might have important implications for effective caribou conservation and forest
      management. 

PMID- 24101981
TI  - Genetic structure, spatial organization, and dispersal in two populations of bat
      eared foxes.
AB  - We incorporated radio-telemetry data with genetic analysis of bat-eared foxes
      (Otocyon megalotis) from individuals in 32 different groups to examine
      relatedness and spatial organization in two populations in South Africa that
      differed in density, home-range sizes, and group sizes. Kin clustering occurred
      only for female dyads in the high-density population. Relatedness was negatively
      correlated with distance only for female dyads in the high-density population,
      and for male and mixed-sex dyads in the low-density population. Home-range
      overlap of neighboring female dyads was significantly greater in the high
      compared to low-density population, whereas overlap within other dyads was
      similar between populations. Amount of home-range overlap between neighbors was
      positively correlated with genetic relatedness for all dyad-site combinations,
      except for female and male dyads in the low-density population. Foxes from all
      age and sex classes dispersed, although females (mostly adults) dispersed farther
      than males. Yearlings dispersed later in the high-density population, and overall
      exhibited a male-biased dispersal pattern. Our results indicated that genetic
      structure within populations of bat-eared foxes was sex-biased, and was
      interrelated to density and group sizes, as well as sex-biases in philopatry and
      dispersal distances. We conclude that a combination of male-biased dispersal
      rates, adult dispersals, and sex-biased dispersal distances likely helped to
      facilitate inbreeding avoidance in this evolutionarily unique species of Canidae.

PMID- 24101982
TI  - Effective sociodemographic population assessment of elusive species in ecology
      and conservation management.
AB  - Wildlife managers are urgently searching for improved sociodemographic population
      assessment methods to evaluate the effectiveness of implemented conservation
      activities. These need to be inexpensive, appropriate for a wide spectrum of
      species and straightforward to apply by local staff members with minimal
      training. Furthermore, conservation management would benefit from single
      approaches which cover many aspects of population assessment beyond only density
      estimates, to include for instance social and demographic structure, movement
      patterns, or species interactions. Remote camera traps have traditionally been
      used to measure species richness. Currently, there is a rapid move toward using
      remote camera trapping in density estimation, community ecology, and conservation
      management. Here, we demonstrate such comprehensive population assessment by
      linking remote video trapping, spatially explicit capture-recapture (SECR)
      techniques, and other methods. We apply it to three species: chimpanzees Pan
      troglodytes troglodytes, gorillas Gorilla gorilla gorilla, and forest elephants
      Loxodonta cyclotis in Loango National Park, Gabon. All three species exhibited
      considerable heterogeneity in capture probability at the sex or group level and
      density was estimated at 1.72, 1.2, and 1.37 individuals per km(2) and male to
      female sex ratios were 1:2.1, 1:3.2, and 1:2 for chimpanzees, gorillas, and
      elephants, respectively. Association patterns revealed four, eight, and 18
      independent social groups of chimpanzees, gorillas, and elephants, respectively:
      key information for both conservation management and studies on the species'
      ecology. Additionally, there was evidence of resident and nonresident elephants
      within the study area and intersexual variation in home range size among
      elephants but not chimpanzees. Our study highlights the potential of combining
      camera trapping and SECR methods in conducting detailed population assessments
      that go far beyond documenting species diversity patterns or estimating single
      species population size. Our study design is widely applicable to other species
      and spatial scales, and moderately trained staff members can collect and process
      the required data. Furthermore, assessments using the same method can be extended
      to include several other ecological, behavioral, and demographic aspects: fission
      and fusion dynamics and intergroup transfers, birth and mortality rates, species
      interactions, and ranging patterns. 

PMID- 24101983
TI  - Climate change and plant dispersal along corridors in fragmented landscapes of
      Mesoamerica.
AB  - Climate change is a threat to biodiversity, and adaptation measures should be
      considered in biodiversity conservation planning. Protected areas (PA) are
      expected to be impacted by climate change and improving their connectivity with
      biological corridors (BC) has been proposed as a potential adaptation measure,
      although assessing its effectiveness remains a challenge. In Mesoamerica, efforts
      to preserve the biodiversity have led to the creation of a regional network of PA
      and, more recently, BC. This study evaluates the role of BC for facilitating
      plant dispersal between PA under climate change in Mesoamerica. A spatially
      explicit dynamic model (cellular automaton) was developed to simulate species
      dispersal under different climate and conservation policy scenarios. Plant
      functional types (PFT) were defined based on a range of dispersal rates and
      vegetation types to represent the diversity of species in the region. The impacts
      of climate change on PA and the role of BC for dispersal were assessed spatially.
      Results show that most impacted PA are those with low altitudinal range in hot,
      dry, or high latitude areas. PA with low altitudinal range in high cool areas
      benefit the most from corridors. The most important corridors cover larger areas
      and have high altitude gradients. Only the fastest PFT can keep up with the
      expected change in climate and benefit from corridors for dispersal. We conclude
      that the spatial assessment of the vulnerability of PA and the role of corridors
      in facilitating dispersal can help conservation planning under a changing
      climate. 

PMID- 24101984
TI  - Gamete production patterns, ploidy, and population genetics reveal evolutionary
      significant units in hybrid water frogs (Pelophylax esculentus).
AB  - The European water frog Pelophylax esculentus is a natural hybrid between P.
      lessonae (genotype LL) and P. ridibundus (RR). It reproduces through
      hybridogenesis, eliminating one parental genome from its germline and producing
      gametes containing the genome of the other parental species. According to
      previous studies, this elimination and transmission pattern is very diverse. In
      mixed populations, where only diploid hybrids (LR) live in sympatry and mate with
      one or both parental species, the excluded genome varies among regions, and the
      remaining genome is transmitted clonally to haploid gametes. In all-hybrid
      populations consisting of diploid (LR) and triploid (LLR and/or LRR) frogs,
      diploid individuals also produce gametes clonally (1n in males, 2n in females),
      whereas triploids eliminate the genome they have in single copy and produce
      haploid gametes containing the recombined other genome. However, here, too,
      regional differences seem to exist, and some triploids have been reported to
      produce diploid gametes. In order to systematically study such regional and
      genotype differences in gamete production, their potential origin, and their
      consequences for the breeding system, we sampled frogs from five populations in
      three European countries, performed crossing experiments, and investigated the
      genetic variation through microsatellite analysis. For four populations, one in
      Poland, two in Germany, and one in Slovakia, our results confirmed the
      elimination and transmission pattern described above. In one Slovakian
      population, however, we found a totally different pattern. Here, triploid males
      (LLR) produce sperm with a clonally transmitted diploid LL genome, rather than a
      haploid recombined L genome, and LR females clonally produce haploid R eggs,
      rather than diploid LR eggs. These differences among the populations in gamete
      production go along with differences in genomotype composition, breeding system
      (i.e., the way triploids are produced), and genetic variation. These differences
      are strong evidence for a polyphyletic origin of triploids. Moreover, our
      findings shed light on the evolutionary potential inherent to the P. esculentus
      complex, where rare events due to untypical gametogenetic processes can lead to
      the raise, the perpetuation, and the dispersion of new evolutionary significant
      lineages which may also deserve special conservation measures. 

PMID- 24101985
TI  - Are heat waves susceptible to mitigate the expansion of a species progressing
      with global warming?
AB  - A number of organisms, especially insects, are extending their range in response
      of the increasing trend of warmer temperatures. However, the effects of more
      frequent climatic anomalies on these species are not clearly known. The pine
      processionary moth, Thaumetopoea pityocampa, is a forest pest that is currently
      extending its geographical distribution in Europe in response to climate warming.
      However, its population density largely decreased in its northern expansion range
      (near Paris, France) the year following the 2003 heat wave. In this study, we
      tested whether the 2003 heat wave could have killed a large part of egg masses.
      First, the local heat wave intensity was determined. Then, an outdoor experiment
      was conducted to measure the deviation between the temperatures recorded by
      weather stations and those observed within sun-exposed egg masses. A second
      experiment was conducted under laboratory conditions to simulate heat wave
      conditions (with night/day temperatures of 20/32 degrees C and 20/40 degrees C
      compared to the control treatment 13/20 degrees C) and measure the potential
      effects of this heat wave on egg masses. No effects were noticed on egg
      development. Then, larvae hatched from these egg masses were reared under mild
      conditions until the third instar and no delayed effects on the development of
      larvae were found. Instead of eggs, the 2003 heat wave had probably affected
      directly or indirectly the young larvae that were already hatched when it
      occurred. Our results suggest that the effects of extreme climatic anomalies
      occurring over narrow time windows are difficult to determine because they
      strongly depend on the life stage of the species exposed to these anomalies.
      However, these effects could potentially reduce or enhance the average warming
      effects. As extreme weather conditions are predicted to become more frequent in
      the future, it is necessary to disentangle the effects of the warming trend from
      the effects of climatic anomalies when predicting the response of a species to
      climate change. 

PMID- 24101986
TI  - Functional traits, the phylogeny of function, and ecosystem service
      vulnerability.
AB  - People depend on benefits provided by ecological systems. Understanding how these
      ecosystem services - and the ecosystem properties underpinning them - respond to
      drivers of change is therefore an urgent priority. We address this challenge
      through developing a novel risk-assessment framework that integrates ecological
      and evolutionary perspectives on functional traits to determine species' effects
      on ecosystems and their tolerance of environmental changes. We define Specific
      Effect Function (SEF) as the per-gram or per capita capacity of a species to
      affect an ecosystem property, and Specific Response Function (SRF) as the ability
      of a species to maintain or enhance its population as the environment changes.
      Our risk assessment is based on the idea that the security of ecosystem services
      depends on how effects (SEFs) and tolerances (SRFs) of organisms - which both
      depend on combinations of functional traits - correlate across species and how
      they are arranged on the species' phylogeny. Four extreme situations are
      theoretically possible, from minimum concern when SEF and SRF are neither
      correlated nor show a phylogenetic signal, to maximum concern when they are
      negatively correlated (i.e., the most important species are the least tolerant)
      and phylogenetically patterned (lacking independent backup). We illustrate the
      assessment with five case studies, involving both plant and animal examples.
      However, the extent to which the frequency of the four plausible outcomes, or
      their intermediates, apply more widely in real-world ecological systems is an
      open question that needs empirical evidence, and suggests a research agenda at
      the interface of evolutionary biology and ecosystem ecology. 

PMID- 24101987
TI  - Host sex-specific parasites in a functionally dioecious fig: a preference way of
      adaptation to their hosts.
AB  - Host-parasites interaction is a common phenomenon in nature. Diffusive
      coevolution might maintain stable cooperation in a fig-fig wasps system, in which
      the exploiter might diversify their genotype, phenotype, or behavior as a result
      of competition with pollinator, whereas the figs change flower syconia, fruits
      thickness, and syconia structure. In functionally dioecious Ficus auriculata,
      male figs and female figs contain two types of florets on separate plant, and
      share high similarities in outside morphology. Apocryptophagus (Sycophaginae,
      Chalcidoidea, Hymenoptera) is one of few groups of nonpollinating fig wasps that
      can reproduce within both male and female figs. On the basis of the morphology
      and DNA barcoding, evidence from partial sequences of mitochondrial cytochrome c
      oxidase I and nuclear internal transcribed spacer 2, we found that there are two
      nonsibling Apocryptophagus species living on male and female F. auriculata figs,
      respectively. We estimated that these two species diverged about 19.2 million
      years ago. Our study suggests that the host shift from Ficus variegate or Ficus
      prostrata fig species to male figs is a preference way for Apocryptophagus wasps
      to adapt to the separation of sexual function in diecious figs. Furthermore, to
      escape the disadvantage or sanction impact of the host, the exploiter
      Apocryptophagus wasps can preferably adapt to exploiting each sex of the figs, by
      changing their oviposition, niche shift, and habitat. 

PMID- 24101988
TI  - Coevolutionary analyses of the relationships between piroplasmids and their hard
      tick hosts.
AB  - Host-parasite coevolution is a key driver of biological diversity. To examine the
      evolutionary relationships between piroplasmids and their hard tick hosts, we
      calculated the molecular clock and conducted phylogenetic analyses of both
      groups. Based on our results, we conclude that the divergence time of
      piroplasmids (~56 Mya) is later than divergence time of their hard tick hosts
      (~86 Mya). From analyses of the evolution of both piroplasmid and vector lineages
      and their association, we know that hard ticks transmit piroplasmids with high
      genus specificity and low species specificity. 

PMID- 24101989
TI  - Critical indirect effects of climate change on sub-Antarctic ecosystem
      functioning.
AB  - Sub-Antarctic islands represent critical breeding habitats for land-based top
      predators that dominate Southern Ocean food webs. Reproduction and molting incur
      high energetic demands that are sustained at the sub-Antarctic Prince Edward
      Islands (PEIs) by both inshore (phytoplankton blooms; "island mass effect";
      autochthonous) and offshore (allochthonous) productivity. As the relative
      contributions of these sustenance pathways are, in turn, affected by
      oceanographic conditions around the PEIs, we address the consequences of
      climatically driven changes in the physical environment on this island ecosystem.
      We show that there has been a measurable long-term shift in the carbon isotope
      signatures of the benthos inhabiting the shallow shelf region of the PEIs, most
      likely reflecting a long-term decline in enhanced phytoplankton productivity at
      the islands in response to a climate-driven shift in the position of the sub
      Antarctic Front. Our results indicate that regional climate change has affected
      the balance between allochthonous and autochthonous productivity at the PEIs.
      Over the last three decades, inshore-feeding top predators at the islands have
      shown a marked decrease in their population sizes. Conversely, population sizes
      of offshore-feeding predators that forage over great distances from the islands
      have remained stable or increased, with one exception. Population decline of
      predators that rely heavily on organisms inhabiting the inshore region strongly
      suggest changes in prey availability, which are likely driven by factors such as
      fisheries impacts on some prey populations and shifts in competitive interactions
      among predators. In addition to these local factors, our analysis indicates that
      changes in prey availability may also result indirectly through regional climate
      change effects on the islands' marine ecosystem. Most importantly, our results
      indicate that a fundamental shift in the balance between allochthonous and
      autochthonous trophic pathways within this island ecosystem may be detected
      throughout the food web, demonstrating that the most powerful effects of climate
      change on marine systems may be indirect. 

PMID- 24101990
TI  - Y-chromosome evidence supports asymmetric dog introgression into eastern coyotes.
AB  - Hybridization has played an important role in the evolutionary history of Canis
      species in eastern North America. Genetic evidence of coyote-dog hybridization
      based on mitochondrial DNA (mtDNA) is lacking compared to that based on autosomal
      markers. This discordance suggests dog introgression into coyotes has potentially
      been male biased, but this hypothesis has not been formally tested. Therefore, we
      investigated biparentally, maternally, and paternally inherited genetic markers
      in a sample of coyotes and dogs from southeastern Ontario to assess potential
      asymmetric dog introgression into coyotes. Analysis of autosomal microsatellite
      genotypes revealed minimal historical and contemporary admixture between coyotes
      and dogs. We observed only mutually exclusive mtDNA haplotypes in coyotes and
      dogs, but we observed Y-chromosome haplotypes (Y-haplotypes) in both historical
      and contemporary coyotes that were also common in dogs. Species-specific Zfy
      intron sequences of Y-haplotypes shared between coyotes and dogs confirmed their
      homology and indicated a putative origin from dogs. We compared Y-haplotypes
      observed in coyotes, wolves, and dogs profiled in multiple studies, and observed
      that the Y-haplotypes shared between coyotes and dogs were either absent or rare
      in North American wolves, present in eastern coyotes, but absent in western
      coyotes. We suggest the eastern coyote has experienced asymmetric genetic
      introgression from dogs, resulting from predominantly historical hybridization
      with male dogs and subsequent backcrossing of hybrid offspring with coyotes. We
      discuss the temporal and spatial dynamics of coyote-dog hybridization and the
      conditions that may have facilitated the introgression of dog Y-chromosomes into
      coyotes. Our findings clarify the evolutionary history of the eastern coyote. 

PMID- 24101991
TI  - Implications of a temperature increase for host plant range: predictions for a
      butterfly.
AB  - Although changes in phenology and species associations are relatively well
      documented responses to global warming, the potential interactions between these
      phenomena are less well understood. In this study, we investigate the
      interactions between temperature, phenology (in terms of seasonal timing of
      larval growth) and host plant use in the polyphagous butterfly Polygonia c-album.
      We found that the hierarchy of larval performance on three natural host plants
      was not modified by a temperature increase as such. However, larval performance
      on each host plant and temperature treatment was affected by rearing season. Even
      though larvae performed better at the higher temperature regardless of the time
      of the rearing, relative differences between host plants changed with the season.
      For larvae reared late in the season, performance was always better on the
      herbaceous plant than on the woody plants. In this species, it is likely that a
      prolonged warming will lead to a shift from univoltinism to bivoltinism. The
      demonstrated interaction between host plant suitability and season means that
      such a shift is likely to lead to a shift in selective regime, favoring
      specialization on the herbaceous host. Based on our result, we suggest that host
      range evolution in response to temperature increase would in this species be
      highly contingent on whether the population undergoes a predicted shift from one
      to two generations. We discuss the effect of global warming on species
      associations and the outcome of asynchrony in rates of phenological change. 

PMID- 24101992
TI  - Different modes of evolution in males and females generate dichromatism in fairy
      wrens (Maluridae).
AB  - Sexual dichromatism in birds is often attributed to selection for elaboration in
      males. However, evolutionary changes in either sex can result in plumage
      differences between them, and such changes can result in either gains or losses
      of dimorphism. We reconstructed the evolution of plumage colors in both males and
      females of species in Maluridae, a family comprising the fairy-wrens (Malurus,
      Clytomias, Sipodotus), emu-wrens (Stipiturus), and grasswrens (Amytornis). Our
      results show that, across species, males and females differ in their patterns of
      color evolution. Male plumage has diverged at relatively steady rates, whereas
      female coloration has changed dramatically in some lineages and little in others.
      Accordingly, in comparisons against evolutionary models, plumage changes in males
      best fit a Brownian motion (BM) model, whereas plumage changes in females fit an
      Ornstein Uhlenbeck (OU) multioptimum model, with different adaptive peaks
      corresponding to distributions in either Australia or New Guinea. Levels of
      dichromatism were significantly associated with latitude, with greater
      dichromatism in more southerly taxa. Our results suggest that current patterns of
      plumage diversity in fairy-wrens are a product of evolutionary changes in both
      sexes, driven in part by environmental differences across the distribution of the
      family. 

PMID- 24101993
TI  - Local differentiation amidst extensive allele sharing in Oryza nivara and O.
      rufipogon.
AB  - Genetic variation patterns within and between species may change along geographic
      gradients and at different spatial scales. This was revealed by microsatellite
      data at 29 loci obtained from 119 accessions of three Oryza series Sativae
      species in Asia Pacific: Oryza nivara Sharma and Shastry, O. rufipogon Griff.,
      and O. meridionalis Ng. Genetic similarities between O. nivara and O. rufipogon
      across their distribution are evident in the clustering and ordination results
      and in the large proportion of shared alleles between these taxa. However, local
      level species separation is recognized by Bayesian clustering and neighbor
      joining analyses. At the regional scale, the two species seem more differentiated
      in South Asia than in Southeast Asia as revealed by F ST analysis. The presence
      of strong gene flow barriers in smaller spatial units is also suggested in the
      analysis of molecular variance (AMOVA) results where 64% of the genetic variation
      is contained among populations (as compared to 26% within populations and 10%
      among species). Oryza nivara (H E = 0.67) exhibits slightly lower diversity and
      greater population differentiation than O. rufipogon (H E = 0.70). Bayesian
      inference identified four, and at a finer structural level eight, genetically
      distinct population groups that correspond to geographic populations within the
      three taxa. Oryza meridionalis and the Nepalese O. nivara seemed diverged from
      all the population groups of the series, whereas the Australasian O. rufipogon
      appeared distinct from the rest of the species. 

PMID- 24101994
TI  - Nonconsumptive effects in a multiple predator system reduce the foraging
      efficiency of a keystone predator.
AB  - Many studies have demonstrated that the nonconsumptive effect (NCE) of predators
      on prey traits can alter prey demographics in ways that are just as strong as the
      consumptive effect (CE) of predators. Less well studied, however, is how the CE
      and NCE of multiple predator species can interact to influence the combined
      effect of multiple predators on prey mortality. We examined the extent to which
      the NCE of one predator altered the CE of another predator on a shared prey and
      evaluated whether we can better predict the combined impact of multiple predators
      on prey when accounting for this influence. We conducted a set of experiments
      with larval dragonflies, adult newts (a known keystone predator), and their
      tadpole prey. We quantified the CE and NCE of each predator, the extent to which
      NCEs from one predator alters the CE of the second predator, and the combined
      effect of both predators on prey mortality. We then compared the combined effect
      of both predators on prey mortality to four predictive models. Dragonflies caused
      more tadpoles to hide under leaf litter (a NCE), where newts spend less time
      foraging, which reduced the foraging success (CE) of newts. Newts altered tadpole
      behavior but not in a way that altered the foraging success of dragonflies. Our
      study suggests that we can better predict the combined effect of multiple
      predators on prey when we incorporate the influence of interactions between the
      CE and NCE of multiple predators into a predictive model. In our case, the threat
      of predation to prey by one predator reduced the foraging efficiency of a
      keystone predator. Consequently, the ability of a predator to fill a keystone
      role could be compromised by the presence of other predators. 

PMID- 24101995
TI  - Local density and group size interacts with age and sex to determine direction
      and rate of social dispersal in a polygynous mammal.
AB  - Movement away from an area or social group in response to increasing density
      (density-dependent dispersal) is known for most species; why it evolves is
      fundamental to our understanding of ecology and evolution. However, we have yet
      to fully appreciate how individuals of varying conditions (e.g., age and sex)
      might differently consider effects of density (quorum) when deciding to disperse
      or not, and scale dependence in their sense of quorum. We tracked movements of
      all individuals of a naturalized population of feral horses (Equus ferus
      caballus; Sable Island National Park Reserve, Nova Scotia, Canada) during a
      period of rapid population growth (N increased from 375 to 484 horses from 2008
      to 2010). Permanent dispersal from breeding groups (bands) was positively density
      dependent for all age and sex categories with respect to local density
      (horses/km(2), bounded by the 99th percentile of individual movements [8000 m]),
      but was negatively and positively density dependent for males and females,
      respectively, in relation to group (band) size. Dispersal was generally female
      biased, with the exception of foals which moved with their mothers (no sex
      effect), and for yearlings and subadults when band sizes were smaller than
      average, in which case males dispersed at higher rates than females. Dispersal
      distance was positively related to local density. We conclude that dispersal rate
      can be both positively and negatively density dependent for feral horses,
      contingent on the state of individuals and the scale at which quorum with respect
      to choosing to disperse or not is assessed. Scale effects and interactions of
      density-dependent and sex- and age-biased dispersal may have both ecological and
      evolutionary consequences through effects on resource and mate competition. 

PMID- 24101996
TI  - Speciation patterns and processes in the zooplankton of the ancient lakes of
      Sulawesi Island, Indonesia.
AB  - Although studies of ancient lake fauna have provided important insights about
      speciation patterns and processes of organisms in heterogeneous benthic
      environments, evolutionary forces responsible for speciation in the relatively
      homogenous planktonic environment remain largely unexplored. In this study, we
      investigate possible mechanisms of speciation in zooplankton using the freshwater
      diaptomids of the ancient lakes of Sulawesi, Indonesia, as a model system. We
      integrate phylogenetic and population genetic analyses of mitochondrial and
      nuclear genes with morphological and genome size data. Overall, our results
      support the conclusion that colonization order and local adaptation are dominant
      at the large, island scale, whereas at local and intralacustrine scales,
      speciation processes are regulated by gene flow among genetically differentiated
      and locally adapted populations. In the Malili lakes, the diaptomid populations
      are homogenous at nuclear loci, but show two highly divergent mitochondrial
      clades that are geographically restricted to single lakes despite the
      interconnectivity of the lake systems. Our study, based on coalescent simulations
      and population genetic analyses, indicates that unidirectional hybridization
      allows gene flow across the nuclear genome, but prevents the introgression of
      mitochondria into downstream populations. We suggest that hybridization and
      introgression between young lineages is a significant evolutionary force in
      freshwater plankton. 

PMID- 24101997
TI  - Effects of experimental warming on stomatal traits in leaves of maize (Zea may
      L.).
AB  - We examined the warming effects on the stomatal frequency, stomatal aperture size
      and shape, and their spatial distribution pattern of maize (Zea may L.) leaves
      using a light microscope, an electron scanning microscope, and geostatistic
      techniques. A field manipulative experiment was conducted to elevate canopy
      temperature by 2.08 degrees C, on average. We found that experimental warming had
      little effect on stomatal density, but significantly increased stomatal index due
      to the reduction in the number of epidermal cells under the warming treatment.
      Warming also significantly decreased stomatal aperture length and increased
      stomatal aperture width. As a result, warming significantly increased the average
      stomatal aperture area and stomatal aperture circumference. In addition, warming
      dramatically changed the stomatal spatial distribution pattern with a substantial
      increase in the average nearest neighbor distance between stomata on both adaxial
      and abaxial surfaces. The spatial distribution pattern of stomata was scale
      dependent with regular patterns at small scales and random patterns at larger
      scales on both leaf surfaces. Warming caused the stomatal distribution to become
      more regular on both leaf surfaces with smaller L(t) values (Ripley's K-function,
      L(t) is an expectation of zero for any value of t) in the warming plots than the
      control plots. 

PMID- 24101998
TI  - How are plant and fungal communities linked to each other in belowground
      ecosystems? A massively parallel pyrosequencing analysis of the association
      specificity of root-associated fungi and their host plants.
AB  - In natural forests, hundreds of fungal species colonize plant roots. The
      preference or specificity for partners in these symbiotic relationships is a key
      to understanding how the community structures of root-associated fungi and their
      host plants influence each other. In an oak-dominated forest in Japan, we
      investigated the root-associated fungal community based on a pyrosequencing
      analysis of the roots of 33 plant species. Of the 387 fungal taxa observed, 153
      (39.5%) were identified on at least two plant species. Although many mycorrhizal
      and root-endophytic fungi are shared between the plant species, the five most
      common plant species in the community had specificity in their association with
      fungal taxa. Likewise, fungi displayed remarkable variation in their association
      specificity for plants even within the same phylogenetic or ecological groups.
      For example, some fungi in the ectomycorrhizal family Russulaceae were detected
      almost exclusively on specific oak (Quercus) species, whereas other Russulaceae
      fungi were found even on "non-ectomycorrhizal" plants (e.g., Lyonia and Ilex).
      Putatively endophytic ascomycetes in the orders Helotiales and Chaetothyriales
      also displayed variation in their association specificity and many of them were
      shared among plant species as major symbionts. These results suggest that the
      entire structure of belowground plant-fungal associations is described neither by
      the random sharing of hosts/symbionts nor by complete compartmentalization by
      mycorrhizal type. Rather, the colonization of multiple types of mycorrhizal fungi
      on the same plant species and the prevalence of diverse root-endophytic fungi may
      be important features of belowground linkage between plant and fungal
      communities. 

PMID- 24101999
TI  - Supporting crop pollinators with floral resources: network-based phenological
      matching.
AB  - The production of diverse and affordable agricultural crop species depends on
      pollination services provided by bees. Indeed, the proportion of pollinator
      dependent crops is increasing globally. Agriculture relies heavily on the
      domesticated honeybee; the services provided by this single species are under
      threat and becoming increasingly costly. Importantly, the free pollination
      services provided by diverse wild bee communities have been shown to be
      sufficient for high agricultural yields in some systems. However, stable,
      functional wild bee communities require floral resources, such as pollen and
      nectar, throughout their active season, not just when crop species are in flower.
      To target floral provisioning efforts to conserve and support native and managed
      bee species, we apply network theoretical methods incorporating plant and
      pollinator phenologies. Using a two-year dataset comprising interactions between
      bees (superfamily Apoidea, Anthophila) and 25 native perennial plant species in
      floral provisioning habitat, we identify plant and bee species that provide a key
      and central role to the stability of the structure of this community. We also
      examine three specific case studies: how provisioning habitat can provide
      temporally continuous support for honeybees (Apis mellifera) and bumblebees
      (Bombus impatiens), and how resource supplementation strategies might be designed
      for a single genus of important orchard pollinators (Osmia). This framework could
      be used to provide native bee communities with additional, well-targeted floral
      resources to ensure that they not only survive, but also thrive. 

PMID- 24102000
TI  - Generalized additive mixed models for disentangling long-term trends, local
      anomalies, and seasonality in fruit tree phenology.
AB  - Quantifying temporal patterns of ephemeral plant structures such as leaves,
      flowers, and fruits gives insight into both plant and animal ecology. Different
      scales of temporal changes in fruits, for example within- versus across-year
      variability, are driven by different processes, but are not always easy to
      disentangle. We apply generalized additive mixed models (GAMMs) to study a long
      term fruit presence-absence data set of individual trees collected from a high
      altitude Afromontane tropical rain forest site within Bwindi Impenetrable
      National Park (BINP), Uganda. Our primary aim was to highlight and evaluate GAMM
      methodology, and quantify both intra- and interannual changes in fruit
      production. First, we conduct several simulation experiments to study the
      practical utility of model selection and smooth term estimation relevant for
      disentangling intra- and interannual variability. These simulations indicate that
      estimation of nonlinearity and seasonality is generally accurately identified
      using asymptotic theory. Applied to the empirical data set, we found that the
      forest-level fruiting variability arises from both regular seasonality and
      significant interannual variability, with the years 2009-2010 in particular
      showing a significant increase in the presence of fruits-driven by increased
      productivity of most species, and a regular annual peak associated occurring at
      the end of one of the two dry seasons. Our analyses illustrate a statistical
      framework for disentangling short-term increases/decreases in fruiting effort
      while pinpointing specific times in which fruiting is atypical, providing a first
      step for assessing the impacts of regular and irregular (e.g., climate change)
      abiotic covariates on fruiting phenology. Some consequences of the rich diversity
      of fruiting patterns observed here for the population biology of frugivores in
      BINP are also discussed. 

PMID- 24102001
TI  - Extensive sampling of polar bears (Ursus maritimus) in the Northwest Passage
      (Canadian Arctic Archipelago) reveals population differentiation across multiple
      spatial and temporal scales.
AB  - As global warming accelerates the melting of Arctic sea ice, polar bears (Ursus
      maritimus) must adapt to a rapidly changing landscape. This process will
      necessarily alter the species distribution together with population dynamics and
      structure. Detailed knowledge of these changes is crucial to delineating
      conservation priorities. Here, we sampled 361 polar bears from across the center
      of the Canadian Arctic Archipelago spanning the Gulf of Boothia (GB) and
      M'Clintock Channel (MC). We use DNA microsatellites and mitochondrial control
      region sequences to quantify genetic differentiation, estimate gene flow, and
      infer population history. Two populations, roughly coincident with GB and MC, are
      significantly differentiated at both nuclear (F ST = 0.01) and mitochondrial
      (PhiST = 0.47; F ST = 0.29) loci, allowing Bayesian clustering analyses to assign
      individuals to either group. Our data imply that the causes of the mitochondrial
      and nuclear genetic patterns differ. Analysis of mtDNA reveals the matrilineal
      structure dates at least to the Holocene, and is common to individuals throughout
      the species' range. These mtDNA differences probably reflect both genetic drift
      and historical colonization dynamics. In contrast, the differentiation inferred
      from microsatellites is only on the scale of hundreds of years, possibly
      reflecting contemporary impediments to gene flow. Taken together, our data
      suggest that gene flow is insufficient to homogenize the GB and MC populations
      and support the designation of GB and MC as separate polar bear conservation
      units. Our study also provide a striking example of how nuclear DNA and mtDNA
      capture different aspects of a species demographic history. 

PMID- 24102002
TI  - Ecomorphological disparity in an adaptive radiation: opercular bone shape and
      stable isotopes in Antarctic icefishes.
AB  - To assess how ecological and morphological disparity is interrelated in the
      adaptive radiation of Antarctic notothenioid fish we used patterns of opercle
      bone evolution as a model to quantify shape disparity, phylogenetic patterns of
      shape evolution, and ecological correlates in the form of stable isotope values.
      Using a sample of 25 species including representatives from four major
      notothenioid clades, we show that opercle shape disparity is higher in the modern
      fauna than would be expected under the neutral evolution Brownian motion model.
      Phylogenetic comparative methods indicate that opercle shape data best fit a
      model of directional selection (Ornstein-Uhlenbeck) and are least supported by
      the "early burst" model of adaptive radiation. The main evolutionary axis of
      opercle shape change reflects movement from a broad and more symmetrically
      tapered opercle to one that narrows along the distal margin, but with only slight
      shape change on the proximal margin. We find a trend in opercle shape change
      along the benthic-pelagic axis, underlining the importance of this axis for
      diversification in the notothenioid radiation. A major impetus for the study of
      adaptive radiations is to uncover generalized patterns among different groups,
      and the evolutionary patterns in opercle shape among notothenioids are similar to
      those found among other adaptive radiations (three-spined sticklebacks) promoting
      the utility of this approach for assessing ecomorphological interactions on a
      broad scale. 

PMID- 24102003
TI  - Phenological overlap of interacting species in a changing climate: an assessment
      of available approaches.
AB  - Concern regarding the biological effects of climate change has led to a recent
      surge in research to understand the consequences of phenological change for
      species interactions. This rapidly expanding research program is centered on
      three lines of inquiry: (1) how the phenological overlap of interacting species
      is changing, (2) why the phenological overlap of interacting species is changing,
      and (3) how the phenological overlap of interacting species will change under
      future climate scenarios. We synthesize the widely disparate approaches currently
      being used to investigate these questions: (1) interpretation of long-term
      phenological data, (2) field observations, (3) experimental manipulations, (4)
      simulations and nonmechanistic models, and (5) mechanistic models. We present a
      conceptual framework for selecting approaches that are best matched to the
      question of interest. We weigh the merits and limitations of each approach,
      survey the recent literature from diverse systems to quantify their use, and
      characterize the types of interactions being studied by each of them. We
      highlight the value of combining approaches and the importance of long-term data
      for establishing a baseline of phenological synchrony. Future work that scales up
      from pairwise species interactions to communities and ecosystems, emphasizing the
      use of predictive approaches, will be particularly valuable for reaching a
      broader understanding of the complex effects of climate change on the
      phenological overlap of interacting species. It will also be important to study a
      broader range of interactions: to date, most of the research on climate-induced
      phenological shifts has focused on terrestrial pairwise resource-consumer
      interactions, especially those between plants and insects. 

PMID- 24102006
TI  - Lung cancer: an update on current and future diagnostic and treatment techniques.

PMID- 24102007
TI  - Superior sulcus (Pancoast) tumors: current evidence on diagnosis and radical
      treatment.
AB  - Pancoast tumors account for less than 5% of all bronchogenic carcinomas. These
      tumors are located in the apex of the lung and involve through tissue contiguity
      the apical chest wall and/or the structures of the thoracic inlet. The tumors
      become clinically evident with the characteristic symptoms of the "Pancoast
      Tobias syndrome" which includes Claude-Bernard-Horner syndrome, severe pain in
      the shoulder radiating toward the axilla and/or scapula and along the ulnar
      distribution of the upper arm, atrophy of hand and arm muscles and obstruction of
      the subclavian vein resulting in edema of the upper arm. The diagnosis will be
      made by the combination of the characteristic clinical symptoms with the
      radiographic findings of a mass or opacity in the apex of the lung infiltrating
      the 1(st) and/or 2(nd) ribs. A tissue diagnosis of the tumor via CT-guided FNA/B
      should always be available before the initiation of treatment. Bronchoscopy,
      thoracoscopy and biopsy of palpable supraclavicular nodes are alternative ways to
      obtain a tissue diagnosis. Adenocarcinomas account for 2/3 of all Pancoast
      tumors, while the rest of the tumors are squamous cell and large cell carcinomas.
      Magnetic resonance imaging of the thoracic inlet is always recommended to define
      the exact extent of tumor invasion within the thoracic inlet before surgical
      intervention. Pancoast tumors are by definition T3 or T4 tumors. Induction chemo
      radiotherapy is the standard of care for any potentially resectable Pancoast
      tumor followed by an attempt to achieve a complete tumor resection. Resection can
      be made through a variety of anterior and posterior approaches to the thoracic
      inlet. The choice of the approach depends on the location of the tumor (posterior
      - middle - anterior compartment of the thoracic inlet) and the depth/extent of
      invasion. Prognosis depends mainly on T stage of tumor, response to preoperative
      chemo-radiotherapy and completeness of resection. Resection of the invaded
      strictures of the thoracic inlet should me made en bloc with pulmonary parenchyma
      resection, preferably an upper lobectomy. Invasion of the vertebral column is not
      a contraindication for surgery which, however, should be performed in oncologic
      centers with experience in spinal surgery. Surgery for Pancoast tumors is
      associated with 5% mortality rate and the complication rate varies from 7-38%.
      The overall 2-year survival rate after induction chemo-radiotherapy and resection
      varies from 55% to 70%, while the 5-year survival for R0 resections is quite good
      (54-77%). The main pattern of recurrence is that of distant metastases,
      especially in the brain. 

PMID- 24102008
TI  - Advanced bronchoscopic techniques in diagnosis and staging of lung cancer.
AB  - The role of advanced brochoscopic diagnostic techniques in detection and staging
      of lung cancer has steeply increased in recent years. Bronchoscopic imaging
      techniques became widely available and easy to use. Technical improvement led to
      merging in technologies making autofluorescence or narrow band imaging
      incorporated into one bronchoscope. New tools, such as autofluorescence imagining
      (AFI), narrow band imaging (NBI) or fuji intelligent chromo endoscopy (FICE),
      found their place in respiratory endoscopy suites. Development of endobronchial
      ultrasound (EBUS) improved minimally invasive mediastinal staging and diagnosis
      of peripheral lung lesions. Linear EBUS proven to be complementary to
      mediastinoscopy. This technique is now available in almost all high volume
      centers performing bronchoscopy. Radial EBUS with mini-probes and guiding sheaths
      provides accurate diagnosis of peripheral pulmonary lesions. Combining EBUS
      guided procedures with rapid on site cytology (ROSE) increases diagnostic yield
      even more. Electromagnetic navigation technology (EMN) is also widely used for
      diagnosis of peripheral lesions. Future development will certainly lead to new
      improvements in technology and creation of new sophisticated tools for research
      in respiratory endoscopy. Broncho-microscopy, alveoloscopy, optical coherence
      tomography are some of the new research techniques emerging for rapid
      technological development. 

PMID- 24102009
TI  - Adjuvant chemotherapy and radiotherapy in the treatment of non-small cell lung
      cancer (NSCLC).
AB  - Lung cancer is one of the most common human malignancies and remains the leading
      cause of cancer related deaths worldwide. Many recent technological advances led
      to improved diagnostics and staging of lung cancer. With development of new
      treatment options such as targeted therapies there might be improvement in
      progression free survival of patients with advanced stage non-small cell lung
      cancer (NSCLC). Improvement in overall survival is still reserved for selected
      patients and selected treatments. One of the mostly investigated therapeutic
      options is adjuvant treatment. There are many open issues in selection of
      patients and administration of appropriate adjuvant treatment. 

PMID- 24102010
TI  - Surgical approaches of endobronchial neoplasms.
AB  - Endobronchial tumors are a rare entity that presents with different pathological
      findings. The interventional pulmonologist, but also the thoracic surgeon have at
      their disposal the same techniques for diagnosis, however; the two modalities
      differentiate in the treatment approach. Diagnosis evaluation should include
      lymph node evaluation. Minimal invasive techniques under local or general
      anesthesia are usually preferred by the interventional pulmonologists, whereas in
      the surgical approach of the thoracic surgeons the general anesthesia is
      necessary. A more extensive surgical approach either lobotomy or pneumonectomy
      should be performed in cases with positive intrapulmonary lymph nodes. Carinal
      reconstruction should be performed skillfully to get a negative proximal margin
      whenever needed. In the current manuscript we will present the methods of patient
      evaluation and surgical techniques for the management of these lesions. 

PMID- 24102011
TI  - The management of the advanced colorectal cancer: management of the pulmonary
      metastases.
AB  - Pulmonary metastases from colorectal cancer present as systemic manifestation of
      the disease. As a general principle, the presence of metastases predispose to a
      poor prognosis. However, the application of some criteria of "operability"
      permitted the surgical resection resulting in prolonged survival (reported 5-year
      survival up to 50%), in better quality of life and in the cure of some patients.
      When the primary tumor site is controlled, and the metastatic disease is limited
      in lungs without extrapulmonary location (except for resectable or resected
      hepatic lesion) surgical removal is indicated. As significant prognostic factors
      in metastasectomies have been reported the synchronous or metachronous caracter
      of the metastases, the disease free survival, the complete removal of the
      metastases, the thoracic lymph node invasion, the CEA level before metastasectomy
      and 1 month after, the solitary vs. multiple pulmonary metastatic locations, the
      induction chemotherapy, the histological type and differentiation grade, as well
      as the vascular emboli in histopathological examination. Thorough preoperative
      evaluation of the patient includes oncological assessment and respiratory
      functional tests. Alternatively, when the patient is not a good surgical
      candidate, radiofrequency ablation is an option. Many surgical accesses have been
      validated, as posterolateral or lateral or even posterior thoracotomy,
      sternotomy, clamshell incision, and thoracoscopic techniques that offer the
      advantages of less pain, fast recovery, and less morbidity. Though thoracoscopic
      metastasectomies have been questioned concerning to the completeness of
      metastatic removal, no statistical difference in survival has been revealed in
      many series comparing thoracotomy to thoracoscopic techniques. As a conclusion,
      there are many advances in the management of pulmonary metastases from colorectal
      cancer during last decade, the results have been essentially optimized, the role
      of surgery has been established, and the multimodality approach has been
      recognized as the cornerstone of a successful outcome. 

PMID- 24102012
TI  - Treatment of non-small cell lung cancer (NSCLC).
AB  - Radical surgery is the standard of care for fit stage I non-small cell lung
      cancer (NSCLC) patients. Adjuvant treatment should be offered only as part of an
      investigation trial. Stage II and IIIA adjuvant cisplatin-based chemotherapy
      remains the gold standard for completely resected NSCLC tumors. Additionally
      radiotherapy should be offered in patients with N2 lymph nodes. In advanced stage
      IIIB/IV or inoperable NSCLC pts, a multidisciplinary treatment should be offered
      consisted of 4 cycles of cisplatin-based chemotherapy plus a 3(rd) generation
      cytotoxic agent or a cytostatic (anti-EGFR, anti-VEGFR) drug. 

PMID- 24102014
TI  - Intensive care unit and lung cancer: when should we intubate?
AB  - Lung cancer still remains the leading cause of cancer death among males. Several
      new methodologies are being used in the everyday practise for diagnosis and
      staging. Novel targeted therapies are being used and others are being
      investigated. However; early diagnosis still remains the cornerstone for
      efficient treatment and disease management. Lung cancer patients requires in many
      situations intensive care unit (ICU) admission, either due to the necessity for
      supportive care until efficient disease symptom control (respiratory distress due
      to malignant pleural effusion) or disease adverse effect management (massive
      pulmonary embolism). In any case guidelines indicating the patient that has to be
      intubated have not yet been issued. In the current review we will present current
      data and finally present an algorithm based on the current published information
      for lung cancer patients that will probably benefit from admission to the ICU. 

PMID- 24102013
TI  - Malignant pleural mesothelioma: current and future perspectives.
AB  - Mesothelioma still remains an occupational related cancer with severe outcome. It
      is usually diagnosed at advanced stage since it does not demonstrate early
      symptoms. Several efforts have been made towards removing all materials inducing
      mesothelioma in the work setting and new work protection measures have been
      applied. Although we have new targeted treatments and radical surgery as arrows
      in the quiver, the type of mesothelioma and early diagnosis still remain the best
      treatment approach. Novel treatment modalities have been explored and several
      others are already on the way. In the current review we will present current data
      for mesothelioma and future perspectives. 

PMID- 24102015
TI  - Malignant pleural effusion and algorithm management.
AB  - Involvement of the pleura in lung cancer is a common manifestation accompanying
      with reduced life expectancy. Symptoms relief and improvement of the quality of
      life are the primary goals of the management of malignant pleural effusion (MPE).
      Histological confirmation is essential for optimal patient management. Lung
      cancer patients, with life expectancy more than 3 months, resistant to
      chemotherapy should be treated with thoracentesis, intercoastal tube drainage and
      installation of a sclerosant agent or pleurodesis through thoracospopic
      procedures or placement of an indwelling pleura catheter. Talc pleurodesis
      (sterile asbestos-free graded, particle size >15 MUm), as "poudrage" or "slurry"
      still remains the treatment of choice in patients with MPE resistant to
      chemotherapy. 

PMID- 24102016
TI  - Therapeutic procedure in small cell lung cancer.
AB  - Small cell lung cancer (SCLC) represents 12.95% of all lung cancer diagnoses and
      continues to be a major clinical problem, with an aggressive clinical course and
      short disease-free duration after 1st line therapy. Treatment of SCLC remains
      challenging because of its rapid growth and development of drug resistance during
      the course of the disease. Chemotherapy remains the current optimal treatment and
      radical thoracic radiotherapy representing the best treatment option for fit
      patients with LD. Platinum-based chemotherapy is the treatment of choice in
      patients with good performance status, and the effect of cisplatin is important
      for concurrent chemoradiotherapy in LD cause of his radiosensitivity. Patients
      with progress disease after first-line chemotherapy have poor prognosis. Second
      line therapy may produce a modest clinical benefit. A number of targeted agents
      have been investigated in LD and ED, mostly in unselected populations, with
      disappointing results. Prophylactic cranial irradiation (PCI) is recommended only
      for patients who had full response to first line chemotherapy, as target of
      improving overall survival and decreasing possibilities of brain metastases. New
      factors for target therapy are the hope for the management of this systematic
      disease. If we identify these targets for treatment of SCLC and overcome drug
      resistance mechanisms, we will create new chemo-radiotherapy schedules for
      future. 

PMID- 24102018
TI  - Occupational exposure and lung cancer.
AB  - Lung cancer is the leading cause of cancer death for male and the second most
      usual cancer for women after breast cancer. Currently there are available several
      non-specific cytotoxic agents and several targeted agents for lung cancer
      therapy. However; early stage diagnosis is still unavailable and several efforts
      are being made towards this direction. Novel biomarkers are being investigated
      along with new biopsy techniques. The occupational and environmental exposure to
      carcinogenic agents is an everyday phenomenon. Therefore until efficient early
      diagnosis is available, avoidance of exposure to carcinogenic agents is
      necessary. In the current mini-review occupational and environmental carcinogenic
      agents will be presented. 

PMID- 24102019
TI  - Neo-adjuvant chemotherapy in early stage non-small cell lung cancer.
AB  - Lung cancer treatment has evolved during the last decade from the non-specific
      cytotoxic drugs to targeted therapy. New diagnostic equipment such as the
      endobronchial ultrasound bronchoscopy and positron emission tomography has
      enhanced early lung cancer diagnosis. However; we still need additional novel
      biomarkers to assist the already used diagnostic techniques. Surgery is the still
      the best treatment for early lung cancer treatment. Several surgical techniques
      are being used based on the tumour location and cardiothoracic centre's
      experienced. There are however marginal situations where neo-adjuvant
      chemotherapy provides a "pre-step" for the patient. In the current work we will
      provide current data for the patients needing neo-adjuvant chemotherapy before
      proceeding to curative surgery. 

PMID- 24102017
TI  - Lung cancer surgery: an up to date.
AB  - According to the International Agency for Research on Cancer (IARC) GLOBOCAN
      World Cancer Report, lung cancer affects more than 1 million people a year
      worldwide. In Greece according to the 2008 GLOBOCAN report, there were 6,667
      cases recorded, 18% of the total incidence of all cancers in the population.
      Furthermore, there were 6,402 deaths due to lung cancer, 23.5% of all deaths due
      to cancer. Therefore, in our country, lung cancer is the most common and deadly
      form of cancer for the male population. The most important prognostic indicator
      in lung cancer is the extent of disease. The Union Internationale Contre le
      Cancer (UICC) and the American Joint Committee for Cancer Staging (AJCC)
      developed the tumour, node, and metastases (TNM) staging system which attempts to
      define those patients who might be suitable for radical surgery or radical
      radiotherapy, from the majority, who will only be suitable for palliative
      measures. Surgery has an important part for the therapy of patients with lung
      cancer. "Lobectomy is the gold standard treatment". This statement may be
      challenged in cases of stage Ia cancer or in patients with limited pulmonary
      function. In these cases an anatomical segmentectomy with lymph node dissection
      is an acceptable alternative. Chest wall invasion is not a contraindication to
      resection. En-bloc rib resection and reconstruction is the treatment of choice.
      N2 disease represents both a spectrum of disease and the interface between
      surgical and non-surgical treatment of lung cancer Evidence from trials suggests
      that multizone or unresectable N2 disease should be treated primarily by
      chemoradiotherapy. There may be a role for surgery if N2 is downstaged to N0 and
      lobectomy is possible, but pneumonectomy is avoidable. Small cell lung cancer
      (SCLC) is considered a systemic disease at diagnosis, because the potential for
      hematogenous and lymphogenic metastases is very high. The efficacy of surgical
      intervention for SCLC is not clear. Lung cancer resection can be performed using
      several surgical techniques. Video-assisted thoracoscopic surgery (VATS)
      lobectomy is a safe, efficient, well accepted and widespread technique among
      thoracic surgeons. The 5-year survival rate following complete resection of lung
      cancer is stage dependent. Incomplete resection rarely is useful and cures the
      patient. 

PMID- 24102020
TI  - An interview between a pulmonologist and a thoracic surgeon-Pleuroscopy: the
      reappearance of an old definition.

PMID- 24102021
TI  - A Short Period of Ventilation without Perfusion Seems to Reduce Atelectasis
      without Harming the Lungs during Ex Vivo Lung Perfusion.
AB  - To evaluate the lung function of donors after circulatory deaths (DCDs), ex vivo
      lung perfusion (EVLP) has been shown to be a valuable method. We present modified
      EVLP where lung atelectasis is removed, while the lung perfusion is temporarily
      shut down. Twelve pigs were randomized into two groups: modified EVLP and
      conventional EVLP. When the lungs had reached 37 degrees C in the EVLP circuit,
      lung perfusion was temporarily shut down in the modified EVLP group, and positive
      end-expiratory pressure (PEEP) was increased to 10 cm H2O for 10 minutes. In the
      conventional EVLP group, PEEP was increased to 10 cm H2O for 10 minutes with
      unchanged lung perfusion. In the modified EVLP group, the arterial oxygen partial
      pressure (PaO2) was 18.5 +/- 7.0 kPa before and 64.5 +/- 6.0 kPa after the
      maneuver (P < 0.001). In the conventional EVLP group, the PaO2 was 16.8 +/- 3.1
      kPa and 46.8 +/- 2.7 kPa after the maneuver (P < 0.01; P < 0.01). In the modified
      EVLP group, the pulmonary graft weight was unchanged, while in the conventional
      EVLP group, the pulmonary graft weight was significantly increased. Modified EVLP
      with normoventilation of the lungs without ongoing lung perfusion for 10 minutes
      may eliminate atelectasis almost completely without harming the lungs. 

PMID- 24102023
TI  - Accuracy of diagnostic biopsy for cutaneous melanoma: implications for surgical
      oncologists.
AB  - BACKGROUND AND OBJECTIVES: While excisional biopsy is recommended to diagnose
      cutaneous melanoma, various biopsy techniques are used in practice. We undertook
      this study to identify how frequently final tumor stage and treatment
      recommendations changed from diagnostic biopsy to final histopathology after wide
      local excision (WLE). METHODS: We compared the histopathology of the
      dermatopathologist-reviewed diagnostic biopsy and final WLE in 332 cutaneous
      melanoma patients. RESULTS: Tumor sites were extremity (51%), trunk (33%), and
      head/neck (16%). Initial biopsy types were excisional (56%), punch (21%), shave
      (18%), and incisional (5%). Most diagnostic biopsies were margin positive
      regardless of technique, and 36% of patients had residual melanoma on WLE. T
      stage changed in 8% of patients, of whom 59% were diagnosed by punch biopsy, 15%
      by incisional biopsy, 15% by shave biopsy, and 11% by excisional biopsy (P <
      0.0001). Treatment recommendations changed in 6%: 2% after excisional biopsy, 5%
      after shave biopsy, 18% after punch biopsy, and 18% after incisional biopsy (P <
      0.0001). CONCLUSIONS: Although most biopsy margins were positive, T-stage and
      treatment changed for only a minority of melanoma patients. Our data provide
      valuable information to inform patient discussion regarding the likelihood of a
      change in prognosis and the need for secondary procedures after WLE. These data
      support the superiority of dermatopathologist-reviewed excisional biopsy when
      feasible.

PMID- 24102022
TI  - Physical activity and screen time in metabolically healthy obese phenotypes in
      adolescents and adults.
AB  - INTRODUCTION: The purpose of this study was to examine levels of physical
      activity (PA) and screen time (ST) in metabolically healthy obese (MHO) and
      metabolically unhealthy obese (MUO) adolescents and adults. METHODS: NHANES data
      from obese adolescents (12-18 years, BMI z-score >= 95th percentile) and adults
      (19-85 years, BMI >= 30 kg/m(2)) were pooled from 2003-2005 cycles. Metabolic
      phenotypes were categorized as MHO (0 or 1 cardiometabolic risk factor;
      triglycerides, HDL-C, blood pressure, or glucose) or MUO (>=2 cardiometabolic
      risk factors). Logistic regression models estimated associations between
      phenotype and PA/ST adjusted for age, gender, BMI, race/ethnicity, menopausal
      status, and NHANES cycle. RESULTS: Among adolescents, PA was not associated with
      MHO. In contrast, MHO adults 19-44 years were 85% more likely to engage in active
      transportation and 2.7 times more likely to be involved in light intensity usual
      daily activity versus sitting. For each minute per day, adults 45-85 years were
      36% more likely to have the MHO phenotype with higher levels of moderate PA. ST
      was not associated with metabolic phenotypes in adolescents or adults.
      CONCLUSION: The current study provides evidence that PA, but not ST, differs
      between MHO and MUO in adults, but not in adolescents. Future studies are needed
      to confirm results.

PMID- 24102024
TI  - Engaging nurses in research for a randomized clinical trial of a behavioral
      health intervention.
AB  - Nurse involvement in research is essential to the expansion of nursing science
      and improved care for patients. The research participation challenges encountered
      by nurses providing direct care (direct care nurses) include balancing patient
      care demands with research, adjusting to fluctuating staff and patient volumes,
      working with interdisciplinary personnel, and feeling comfortable with their
      knowledge of the research process. The purpose of this paper is to describe
      efforts to engage nurses in research for the Stories and Music for
      Adolescent/Young Adult Resilience during Transplant (SMART) study. SMART was an
      NIH-funded, multisite, randomized, behavioral clinical trial of a music therapy
      intervention for adolescents/young adults (AYA) undergoing stem cell transplant
      for an oncology condition. The study was conducted at 8 sites by a large
      multidisciplinary team that included direct care nurses, advanced practice
      nurses, and nurse researchers, as well as board-certified music therapists,
      clinical research coordinators, and physicians. Efforts to include direct care
      nurses in the conduct of this study fostered mutual respect across disciplines in
      both academic and clinical settings. 

PMID- 24102025
TI  - Complexity and health coaching: synergies in nursing.
AB  - Health care professionals are increasingly aware that persons are complex and
      live in relation with other complex human communities and broader systems.
      Complex beings and systems are living and evolving in nonlinear ways through a
      process of mutual influence. Traditional standardized approaches in chronic
      disease management do not address these non-linear linkages and the meaning and
      changes that impact day-to-day life and caring for self and family. The RN health
      coach role described in this paper addresses the complexities and ambiguities for
      persons living with chronic illness in order to provide person-centered care and
      support that are unique and responsive to the context of persons' lives. Informed
      by complexity thinking and relational inquiry, the RN health coach is an emergent
      innovation of creative action with community and groups that support persons as
      they shape their health and patterns of living. 

PMID- 24102026
TI  - Variation in Functional Independence among Stroke Survivors Having Fatigue and
      Depression.
AB  - Objective. This study evaluated variation in functional independence in
      activities of daily living (ADL) and instrumental activities of daily living
      (IADL) among individuals with poststroke fatigue (PSF) and poststroke depression
      (PSD). Methods. A cross-sectional survey involved 65 consenting poststroke
      survivors who were purposively recruited from physiotherapy clinics of the
      University College Hospital, Ibadan, Adeoyo Maternity Teaching Hospital, Ibadan,
      and Federal Medical Center, Gusau. Participants were assessed for symptoms of PSD
      with short geriatric depression scale-15, PSF with fatigue severity scale, ADL
      with Barthel Index and IADL with Nottingham extended ADL scale. Data analysis was
      done using Chi-square and unpaired t-test with significance level being 0.05.
      Results. Participants' age ranged from 58 to 80 years. PSD alone (P = 0.002) and
      both PSF and PSD (P = 0.02) were significantly associated with ADL, while PSF
      alone was not (P = 0.233). PSD alone (P = 0.001) and both PSF and PSD (P = 0.001)
      significantly negatively affected IADL, while PSF alone had no significant effect
      (P = 0.2). Conclusions. Participants with PSD alone and those with both PSF and
      PSD had lower functional independence in ADL and IADL. 

PMID- 24102027
TI  - Effect of intensive blood pressure control on cardiovascular remodeling in
      hypertensive patients with nephrosclerosis.
AB  - Pulse pressure (PP), a marker of arterial system properties, has been linked to
      cardiovascular (CV) complications. We examined (a) association between unit
      changes of PP and (i) composite CV outcomes and (ii) development of left
      ventricular hypertrophy (LVH) and (b) effect of mean arterial pressure (MAP)
      control on rate of change in PP. We studied 1094 nondiabetics with
      nephrosclerosis in the African American Study of Kidney Disease and Hypertension.
      Subjects were randomly assigned to usual MAP goal (102-107 mmHg) or a lower MAP
      goal (<=92 mmHg) and randomized to beta-blocker, angiotensin converting enzyme
      inhibitor, or calcium channel blocker. After covariate adjustment, a higher PP
      was associated with increased risk of CV outcome (RR = 1.28, CI = 1.11-1.47, P <
      0.01) and new LVH (RR = 1.26, CI = 1.04-1.54, P = 0.02). PP increased at a
      greater rate in the usual than in lower MAP groups (slope +/- SE: 1.08 +/- 0.15
      versus 0.42 +/- 0.15 mmHg/year, P = 0.002), but not by the antihypertensive
      treatment assignment. Observations indicate that control to a lower MAP slows the
      progression of PP, a correlate of cardiovascular remodeling and complications,
      and may be beneficial to CV health. 

PMID- 24102028
TI  - A review of the effects of physical activity and exercise on cognitive and brain
      functions in older adults.
AB  - Studies supporting the notion that physical activity and exercise can help
      alleviate the negative impact of age on the body and the mind abound. This
      literature review provides an overview of important findings in this fast growing
      research domain. Results from cross-sectional, longitudinal, and intervention
      studies with healthy older adults, frail patients, and persons suffering from
      mild cognitive impairment and dementia are reviewed and discussed. Together these
      finding suggest that physical exercise is a promising nonpharmaceutical
      intervention to prevent age-related cognitive decline and neurodegenerative
      diseases. 

PMID- 24102029
TI  - Influence of peripheral artery disease and statin therapy on apolipoprotein
      profiles.
AB  - Apolipoprotein B is a stronger predictor of myocardial infarction than LDL
      cholesterol, and it is inversely related to physical activity and modifiable with
      exercise training. As such, apolipoprotein measures may be of particular
      relevance for subjects with PAD and claudication. We compared plasma
      apolipoprotein profiles in 29 subjects with peripheral artery disease (PAD) and
      intermittent claudication and in 39 control subjects. Furthermore, we compared
      the plasma apolipoprotein profiles of subjects with PAD either treated (n = 17)
      or untreated (n = 12) with statin medications. For the apolipoprotein subparticle
      analyses, subjects with PAD had higher age-adjusted Lp-B:C (P < 0.05) and lower
      values of Lp-A-I:A-II (P < 0.05) than controls. The PAD group taking statins had
      lower age-adjusted values for apoB (P < 0.05), Lp-A-II:B:C:D:E (P < 0.05), Lp-B:E
      + Lp-B:C:E (P < 0.05), Lp-B:C (P < 0.05), and Lp-A-I (P < 0.05) than the
      untreated PAD group. Subjects with PAD have impaired apolipoprotein profiles than
      controls, characterized by Lp-B:C and Lp-A-I:A-II. Furthermore, subjects with PAD
      on statin medications have a more favorable risk profile, particularly noted in
      multiple apolipoprotein subparticles. The efficacy of statin therapy to improve
      cardiovascular risk appears more evident in the apolipoprotein sub-particle
      profile than in the more traditional lipid profile of subjects with PAD and
      claudication. This trial is registered with ClinicalTrials.gov NCT00618670. 

PMID- 24102030
TI  - Addressing the younger age at onset in breast cancer patients in Asia: an age
      period-cohort analysis of fifty years of quality data from the international
      agency for research on cancer.
AB  - Introduction. There is an established fact that Asian breast cancer patients are,
      on average, younger than their European counterparts. This study aimed to utilize
      the data from the Cancer Incidence in Five Continents I through XIII (published
      by the International Agency for Research on Cancer) to examine what contributes
      to the younger age at onset in the Asian population. Material and Methods. Data
      (number of breast cancer cases and corresponding population figures) for 29
      registries in Europe and 9 registries in Asia for the period of 1953-2002 was
      accessioned and pooled to form two distinct populations, Asia and Europe. The age
      specific rates were defined and analyzed cross-sectionally (period wise) and
      longitudinally (cohort wise). The magnitude and the pattern of age specific rates
      were analyzed using the age-period-cohort analysis. The constrained generalized
      linear model with a priority assumption of cohort effect as contributing factor
      to changing rates was used to analyze the data. Result. During the last 50 years,
      the rate of breast cancer increased for both populations with an estimated annual
      percent change of 1.03% (with 95% CI of 1.029, 1.031) for Asia and 1.016% (95% CI
      of 1.015, 1.017) for Europe. There were stronger cohort effects in the magnitude
      of rates among the Asian population compared to the European population. The
      cohort effects, expressed as the rate ratio with cohort born in 1970 as
      reference, ranged from 0.06 (95% CI 0.05, 0.08) to 0.94 (95% CI 0.93, 0.96) for
      Asians and 0.35 (95% CI 0.33, 0.36) to 1.03 (95% CI 1.02, 1.04) for Europeans.
      The estimated longitudinal age specific rates (adjusted for cohort and period
      effects) showed similar patterns between the two populations. Conclusion. It was
      concluded that a strong cohort effect contributes to the younger age at onset
      among Asian breast cancer patients. 

PMID- 24102031
TI  - Scrotal abscess as initial presentation of squamous cell carcinoma.
AB  - We report a case of scrotal squamous cell carcinoma in a 67-year-old man that
      presented as a recurrent nonhealing scrotal abscess. Radical scrotectomy and
      bilateral simple orchiectomy were performed. A pudendal thigh flap was used for
      wound closure. To our knowledge, this is the first report of its use after
      radical surgery for scrotal cancer. The clinical features, staging, and treatment
      of scrotal squamous cell carcinoma are reviewed. In this report, we highlight the
      importance of including scrotal cancer in the differential diagnosis when
      evaluating a scrotal abscess. 

PMID- 24102032
TI  - Intracardiac echocardiography guided transeptal catheter injection of
      microspheres for assessment of cerebral microcirculation in experimental models.
AB  - The use of microspheres for the determination of regional microvascular blood
      flow (RMBF) has previously used different approaches. This study presents for the
      first time the intracardiac injection of microspheres using transeptal puncture
      under intracardiac echocardiography guidance. Five Merino sheep were instrumented
      and cardiovascularly supported according to local guidelines. Two catheter
      sheaths into the internal jugular vein facilitated the introduction of an
      intracardiac probe and transeptal catheter, respectively. Five million colour
      coded microspheres were injected into the left atrium via this catheter. After
      euthanasia the brain was used as proof of principle and the endpoint for
      determination of microcirculation at different time points. Homogeneous
      allocation of microspheres to different regions of the brain was found over time.
      Alternate slices from both hemispheres showed the following flow ranges: for
      slice 02; 0.57-1.02 mL/min/g, slice 04; 0.45-1.42 mL/min/g, slice 06; 0.35-1.87
      mL/min/g, slice 08; 0.46-1.77 mL/min/g, slice 10; 0.34-1.28 mL/min/g. A mixed
      effect regression model demonstrated that the confidence interval did include
      zero suggesting that the apparent variability intra- and intersubject was not
      statistically significant, supporting the stability and reproducibility of the
      injection technique. This study demonstrates the feasibility of the transeptal
      injection of microspheres, showing a homogeneous distribution of blood flow
      through the brain unchanged over time and has established a new interventional
      model for the measurement of RMBF in ovine models. 

PMID- 24102033
TI  - Thromboangiitis Obliterans (Buerger's Disease)-Current Practices.
AB  - Thromboangiitis obliterans (TAO) is a nonatherosclerotic, segmental inflammatory
      disease that most commonly affects the small and medium-sized arteries and veins
      in the upper and lower extremities. Cigarette smoking has been implicated as the
      main etiology of the disease. In eastern parts of the world TAO forms 40-60% of
      peripheral vascular diseases. Clinical features and angiographic finding are the
      basis of early diagnosis of TAO. Abstinence from smoking is the only definitive
      treatment to prevent disease progression. Medical management in form of aspirin,
      pentoxyfylline, cilostazol, and verapamil increase pain-free walking distance in
      intermittent claudication, but long term usage fails to prevent disease
      progression in patients who continue to smoke. Surgical treatment in form of
      revascularization, lumbar sympathectomy, omentopexy, and Ilizarov techniques help
      reduce pain and promote healing of trophic changes. Newer treatment modalities
      like spinal cord stimulation, prostacyclin, bosentan, VEGF, and stem cell therapy
      have shown promising results. Latest treatment options include peripheral
      mononuclear stem cell, and adipose tissue derived mononuclear stem cells have
      been shown to be effective in preventing disease progression, decrease major
      amputation rates, and improving quality of life. 

PMID- 24102035
TI  - Knowledge, Health Beliefs, and Self-Efficacy regarding Osteoporosis in
      Perimenopausal Women.
AB  - The aims of this pilot study were to (1) determine if having a family history of
      osteoporosis impacts knowledge, health beliefs, and self-efficacy regarding
      osteoporosis among perimenopausal women aged 42-52 and to (2) describe the impact
      of an osteoporosis-specific educational intervention had on the knowledge, health
      beliefs, and self-efficacy of this population. Participants completed three
      surveys measuring knowledge, health beliefs, and self-efficacy related to
      osteoporosis before and two months after the educational program. At baseline, no
      differences were noted in knowledge of osteoporosis among women with and without
      a family history of osteoporosis, although women with a family history perceived
      a greater susceptibility for developing osteoporosis than women without the
      family history. Findings indicate that both groups increased in knowledge of
      osteoporosis (P < .001). Benefits of calcium increased in the women without a
      family history of osteoporosis (P < .001) and benefits of exercise increase in
      women with a family history of osteoporosis (P = .007). There were no significant
      statistical findings regarding self-efficacy between the two groups of women.
      Findings indicate that an osteoporosis-specific educational program improves
      perimenopausal women's knowledge and some health beliefs. 

PMID- 24102036
TI  - Malignancy risk assessment in patients with thyroid nodules using classification
      and regression trees.
AB  - Purpose. We sought to investigate the utility of classification and regression
      trees (CART) classifier to differentiate benign from malignant nodules in
      patients referred for thyroid surgery. Methods. Clinical and demographic data of
      271 patients referred to the Sadoughi Hospital during 2006-2011 were collected.
      In a two-step approach, a CART classifier was employed to differentiate patients
      with a high versus low risk of thyroid malignancy. The first step served as the
      screening procedure and was tailored to produce as few false negatives as
      possible. The second step identified those with the lowest risk of malignancy,
      chosen from a high risk population. Sensitivity, specificity, positive and
      negative predictive values (PPV and NPV) of the optimal tree were calculated.
      Results. In the first step, age, sex, and nodule size contributed to the optimal
      tree. Ultrasonographic features were employed in the second step with
      hypoechogenicity and/or microcalcifications yielding the highest discriminatory
      ability. The combined tree produced a sensitivity and specificity of 80.0% (95%
      CI: 29.9-98.9) and 94.1% (95% CI: 78.9-99.0), respectively. NPV and PPV were
      66.7% (41.1-85.6) and 97.0% (82.5-99.8), respectively. Conclusion. CART
      classifier reliably identifies patients with a low risk of malignancy who can
      avoid unnecessary surgery. 

PMID- 24102034
TI  - Receptor for advanced glycation end products and its involvement in inflammatory
      diseases.
AB  - The receptor for advanced glycation end products (RAGE) is a transmembrane
      receptor of the immunoglobulin superfamily, capable of binding a broad repertoire
      of ligands. RAGE-ligands interaction induces a series of signal transduction
      cascades and lead to the activation of transcription factor NF-kappaB as well as
      increased expression of cytokines, chemokines, and adhesion molecules. These
      effects endow RAGE with the role in the signal transduction from pathogen
      substrates to cell activation during the onset and perpetuation of inflammation.
      RAGE signaling and downstream pathways have been implicated in a wide spectrum of
      inflammatory-related pathologic conditions such as arteriosclerosis, Alzheimer's
      disease, arthritis, acute respiratory failure, and sepsis. Despite the
      significant progress in other RAGE studies, the functional importance of the
      receptor in clinical situations and inflammatory diseases still remains to be
      fully realized. In this review, we will summarize current understandings and
      lines of evidence on the molecular mechanisms through which RAGE signaling
      contributes to the pathogenesis of the aforementioned inflammation-associated
      conditions. 

PMID- 24102037
TI  - HER-2 gene amplification in human breast cancer without concurrent HER-2 over
      expression.
AB  - BACKGROUND: Testing for human epidermal growth factor receptor-2 (HER-2) in
      breast cancer is performed by either immunohistochemistry (IHC) or in situ
      hybridization (ISH). The growth factor receptor-bound protein-7 (GRB7) gene is in
      close proximity to HER-2 on chromosome 17q11-12 and codes a signal transduction
      molecule shown to be an independent adverse marker in breast cancer. METHODS: HER
      2 and GRB7 protein expression from 613 frozen breast tumors was determined by
      Western analysis. HER-2 protein results were confirmed with IHC. Commercial HER-2
      FISH was performed on a subset of tumors with multi-probe FISH used to assess the
      extent of HER-2 gene amplification. mRNA expression was determined by Multi-plex
      RT-PCR. RESULTS: Seven tumors with GRB7 protein over-expression scored HER-2 FISH
      amplified but had no HER-2 protein over-expression. Four of the 7 tumors showed
      elevated GRB7 but not HER-2 mRNA over-expression. The breast cancer cell line
      HCC3153 did not over-express HER-2 protein but showed HER-2 FISH amplification of
      a limited segment around the HER-2 gene. Ten breast cancer tumors from the TCGA
      database had gene copy number increases around HER-2 without HER-2 mRNA or
      protein over-expression. CONCLUSIONS: A subset of human breast cancers that test
      positive with FISH for HER-2 gene amplification do not over-express HER-2
      protein. One mechanism for this discordance is the incomplete amplification of
      the smallest HER-2 region of chromosome 17q11-12, which includes GRB7. HER-2 gene
      amplification without protein over-expression is clinically significant because
      patients with such tumors are unlikely to benefit from HER-2 targeted therapy.

PMID- 24102038
TI  - Rooting and acclimatization of micropropagated marubakaido apple rootstock using
      Adesmia latifolia rhizobia.
AB  - In vitro rooting and the acclimatization of micropropagated rootstocks of apple
      trees is essential for plant development in the field. The aim of this work was
      to assess the use of rhizobia of Adesmia latifolia to promote rooting and
      acclimatization in micropropagated Marubakaido apple rootstock. An experiment
      involving in vitro rooting and acclimatization was performed with four strains of
      rhizobium and two controls, one with and the other without the addition of
      synthetic indoleacetic acid. The inoculated treatments involved the use of
      sterile inoculum and inoculum containing live rhizobia. The most significant
      effects on the rooting rate, primary-root length, number of roots, root length,
      fresh-shoot biomass, and fresh-root biomass were obtained by inoculation with
      strain EEL16010B and with synthetic indole acetic acid. However, there was no
      difference in the growth of apple explants in the acclimatization experiments.
      Strain EEL16010B can be used to induce in vitro rooting of the Marubakaido
      rootstock and can replace the use of synthetic indoleacetic acid in the rooting
      of this cultivar. 

PMID- 24102039
TI  - Tuberculosis examination using whole blood interferon-gamma release assay among
      health care workers in a Japanese hospital without tuberculosis-specific wards.
AB  - Occupational latent tuberculosis infection (LTBI) among health care workers
      (HCWs) is an important public health issue. The objective of this study is to
      assess prevalence and risk factors of LTBI among Japanese HCWs by Quantiferon-TB
      Gold in Tube (QFT-GIT) and the structured questionnaire. This is a cross
      sectional study involving HCWs from a hospital without tuberculosis-specific
      wards, receiving QFT-GIT for LTBI screening. We reviewed medical records of HCWs
      and questioned HCWs about exposure to M. tuberculosis and employment length in
      health care industries. 165 HCWs, approximately 80% of the total hospital staff,
      were enrolled in this study.18 out of 165 subjects had positive results,
      suggesting LTBI prevalence rate of 11%. Multiple regression analysis revealed a
      significant association between the positive or intermediate QFT-GIT results and
      history of contact investigation for tuberculosis. QFT-GIT positivity rate among
      HCWs is higher than among general population in Japan. 

PMID- 24102040
TI  - Bladder cancer discussed on the internet: a systematic analysis of gender
      differences of initial posters on an online discussion board.
AB  - OBJECTIVES: To evaluate gender differences of initial posters in threads dealing
      with bladder cancer on an online discussion board. METHOD: 529 threads opened
      between 09/2005 and 03/2012 were screened on the largest German speaking bladder
      cancer online discussion board. 366 threads fulfilled the requirements for this
      study. Gender, age, number, status of concern and oncological situation of
      initiating posters as well as their motives and language style were analyzed
      following a standardized protocol. RESULTS: Threads were initiated in 45%
      (164/366) by men and in 55% (202/366) by women. Mean age of male initiating
      posters was 50 years and of female posters 44 years (p < 0.001). Of males 80%
      (132/164) were concerned patients and 20% (32/164) relatives or friends. Of
      females they were 39% (78/202) and 61% (124/202), respectively (p < 0.001). In
      general motives for initial posting were focused on medical information and did
      not differ between both genders. 81% of the posters asked for medical information
      or therapeutic recommendations regarding diagnosis, treatment and prognosis.
      However, women significantly more often expressed their wish for emotional
      support (p = 0.034) and in tendency wanted to share their experiences with others
      (p = 0.057). Language analysis revealed that women significantly more often used
      a tentative language style than men (p = 0.003). CONCLUSION: Even though women
      are less often affected by bladder cancer, they are more active -especially for
      their concerned family members - on the evaluated discussion board than men.
      Whereas both genders equally often ask for medical information, women more often
      want to share their experiences and look for emotional support.

PMID- 24102041
TI  - Carotid Wallstent placement difficulties encountered in carotid artery stenting.
AB  - PURPOSE: The present study aimed to identify the types of curved lesions that are
      difficult to place Carotid Wallstent (CWS). MATERIALS AND METHODS: The study
      targeted 31 consecutive carotid artery (CA) stenosis underwent carotid artery
      stenting using CWS. CWS placement success rate, stenosis location, lesion
      tortuosity, and relationship with stent placement failures were investigated.
      Lesion tortuosity was defined as the angle formed by 2 tangential lines between
      internal CA and common CA from the inflection point (IP) was defined as the
      center of lesion curvature. Stenosed lesions were classified into type A or B.
      Type A was defined as if the distal end of the stenosis was located proximal to
      the IP at a distance >=0.5 of a vertebral body based on the posterior height of
      the 3rd vertebral body, otherwise was type B. RESULTS: The stent placement
      success rate was 93.5% (29/31). The 2 unsuccessfully stented lesions, both
      lesions were significantly different from other lesions by having a lesion
      tortuosity less than 90 degrees  and by belonging to type B. CONCLUSION: Since
      CWS placement is difficult in patients with CA stenosis located close to the IP
      at a lesion tortuosity <=90 degrees , open-cell stents should be considered as an
      alternative.

PMID- 24102042
TI  - Production of schizophyllan from distiller's dried grains with solubles by
      diverse strains of Schizophyllum commune.
AB  - Eleven diverse strains of Schizophyllan commune were examined for production of
      the biopolymer schizophyllan from agricultural biomass. Strains were grown in
      malt extract (ME) basal medium containing 1% (w/v) distiller's dried grains with
      solubles (DDGS), an abundant coproduct of fuel ethanol production by the dry
      grind process. Ten of 11 strains tested produced more than 2 g schizophyllan/L.
      Two strains, ATCC 20165 and CBS 266.60, produced more than 10 g schizophyllan/L.
      Schizophyllan from these strains was similar to commercial product in terms of
      solution viscosity, molecular weight, and surface tension properties, suggesting
      that they would be equivalent in biomaterial applications. 

PMID- 24102043
TI  - Cerebral air embolism via port catheter and endoscopic retrograde cholangio
      pancreatography.
AB  - BACKGROUND: Cerebral air embolism (CAE) is a critical clinical condition
      necessitating rapid diagnosis and therapeutic measures. METHODS: The authors
      describe two patients with lethal CAE. RESULTS: An 81-year-old man rapidly
      developed coma with tetraplegia. CT-scan revealed prominent CAE whereby the entry
      of the air was via a port catheter for parenteral nutrition. A 45-year-old man
      with severe alcohol-toxic multiple organ damage needed endoscopic retrograde
      cholangio-pancreatography (ERCP) and a second esophagogastroscopy. After an
      epileptic seizure, the CT-scan of the brain showed small amounts of cerebral air
      in the posterior right hemisphere and in the sagittal superior sinus. Despite
      critical care the patient died. CONCLUSION: CAE is a neurocritical emergency
      case. Early CT-scan of the brain can detect air, guide further therapy, and
      contribute to the assessment of the prognosis.

PMID- 24102044
TI  - Anesthetic management of a patient with a giant ovarian tumor containing 83 l of
      fluid.
AB  - We report the anesthetic management of a patient scheduled for tumor resection
      with a giant ovarian tumor containing 83 l of fluid. A 59-year-old woman [height
      154 cm; weight 146 kg (ideal: 52 kg)] with a giant ovarian tumor was scheduled
      for tumor resection. Her preoperative abdominal circumference was 194 cm, which
      made supine positioning difficult. The thoracoabdominal computed tomography
      revealed a right giant cystic ovarian tumor with an estimated mass of 100 kg.
      Evidence of malignant tumor was not observed. In the operation room, she was
      intubated using a video laryngoscope (Airway Scope(r), Hoya, Tokyo, Japan) in a
      semirecumbent position under conscious sedation. Following general anesthesia,
      the tumor fluid was gradually aspirated at a rate of 500 ml/min, and during this
      procedure, spontaneous respiration was preserved with pressure support
      ventilation. After the fluid was drained, the tumor was resected in a supine
      position. There were no major perioperative complications in hemodynamic and
      respiratory status, such as supine hypotensive syndrome or re-expansion pulmonary
      edema. Her weight decreased to 50 kg postoperatively. Maintenance of spontaneous
      respiration and slow aspiration of the tumor fluid prevented respiratory and
      hemodynamic failure and resulted in safe anesthesia management during giant
      ovarian tumor resection. 

PMID- 24102045
TI  - Graphical study of reasons for engagement in physical activity in European Union.
AB  - We collect data on 15 reasons why people in the 27 EU countries engage in
      physical activity, from the European Commission's Special Eurobarometer. A
      graphical output was obtained using classical Principal Component Analysis
      techniques in order to analyse types of motivation in the EU. Cluster Analysis
      method were used to define the interrelationship between the data in the 27
      countries. People in Sweden, Denmark and Finland were the most highly motivated.
      High rates were detected in Austria, Germany, Slovenia, Estonia, Luxembourg and
      Latvia while low rates were found in Bulgaria, Romania, Czech Republic, Greece,
      Spain, Hungary, Italy, Lithuania, Poland, Portugal and Slovakia. The lowest
      motivation rates were in the Netherlands. Regarding the reasons for engaging in
      exercise (a sport or physical activity), we observed two motivation types. The
      first group was related to health and physical appearance while the second was
      associated with social reasons: to be with friends, to better integrate into
      society, to meet people from other cultures. For citizens of Latvia, Bulgaria and
      Romania, health and physical appearance carried greater importance than the
      European average while for citizens of Germany, Finland and Sweden the second
      motivation type was higher than the European average. 

PMID- 24102046
TI  - Presence of anaplastic lymphoma kinase in inflammatory breast cancer.
AB  - Although Inflammatory Breast Cancer (IBC) is recognized as the most metastatic
      variant of locally advanced breast cancer, the molecular basis for the distinct
      clinical presentation and accelerated program of metastasis of IBC is unknown.
      Reverse phase protein arrays revealed activation of the receptor tyrosine kinase,
      anaplastic lymphoma kinase (ALK) and biochemically-linked downstream signaling
      molecules including JAK1/STAT3, AKT, mTor, PDK1, and AMPKbeta in pre-clinical
      models of IBC. To evaluate the clinical relevance of ALK in IBC, analysis of 25
      IBC patient tumors using the FDA approved diagnostic test for ALK genetic
      abnormalities was performed. These studies revealed that 20/25 (80%) had either
      increased ALK copy number, low level ALK gene amplification, or ALK gene
      expression, with a prevalence of ALK alterations in basal-like IBC. One of 25
      patients was identified as having an EML4-ALK translocation. The generality of
      gains in ALK copy number in basal-like breast tumors with IBC characteristics was
      demonstrated by analysis of 479 breast tumors using the TGCA data-base and our
      newly developed 79 IBC-like gene signature. The small molecule dual tyrosine
      kinase cMET/ALK inhibitor, Crizotinib (PF-02341066/Xalkori(r), Pfizer Inc),
      induced both cytotoxicity (IC50 = 0.89 MUM) and apoptosis, with abrogation of
      pALK signaling in IBC tumor cells and in FC-IBC01 tumor xenograft model, a new
      IBC model derived from pleural effusion cells isolated from an ALK(+) IBC
      patient. Based on these studies, IBC patients are currently being evaluated for
      the presence of ALK genetic abnormalities and when eligible, are being enrolled
      into clinical trials evaluating ALK targeted therapeutics. 

PMID- 24102047
TI  - Tumor delivery of chemotherapy combined with inhibitors of angiogenesis and
      vascular targeting agents.
AB  - Numerous angiogenesis-vascular targeting agents have been admitted to the ranks
      of cancer therapeutics; most are used in polytherapy regimens. This review looks
      at recent progress and our own preclinical experience in combining angiogenesis
      inhibitors, mainly acting on VEGF/VEGFR pathways, and vascular targeting agents
      with conventional chemotherapy, discussing the factors that determine the outcome
      of these treatments. Molecular and morphological modifications of the tumor
      microenvironment associated with drug distribution and activity are reviewed.
      Modalities to improve drug delivery and strategies for optimizing combination
      therapy are examined. 

PMID- 24102048
TI  - Detection of Metastatic Disease in Cardiophrenic Lymph Nodes: FDG PET/CT Versus
      Contrast-Enhanced CT and Implications for Staging and Treatment of Disease.
AB  - OBJECTIVE: To determine whether FDG PET/CT was more sensitive than CT in
      detecting metastatic disease in the cardiophrenic space and whether the presence
      of disease in this location would change the staging and clinical management.
      MATERIALS AND METHODS: About 1200 PET/CT scans were retrospectively reviewed over
      20 months for the presence of FDG-avid cardiophrenic lymph nodes. The SUVmax was
      used to quantify the metabolic activity in each of the lymph nodes. The
      radiographic data was used for correlation. A retrospective review of diagnostic
      CT reports performed within a 1-month period of time of the PET/CT in the same
      subset of patients determined whether cardiophrenic lymph nodes were mentioned.
      RESULTS: About 9 (0.8%) of the 1200 studies were found to have FDG-avid
      cardiophrenic lymph nodes (four males and five females with a mean age of 55
      years; range 7-69, median 59). The mean SUVmax was 2.4 (range 1.2-7.9; median
      1.9). Only three of the patients were found to have suspicious lymph nodes on CT.
      The presence of cardiophrenic lymph nodes had the potential to change the staging
      and/or management in three of the patients. CONCLUSION: PET/CT is more accurate
      in the detection of pathologic cardiophrenic lymph nodes than CT, especially when
      they are subcentimeter in size. When present, staging and/or management was
      potentially affected in 33%. Therefore, these nodes should be included in the TNM
      staging classification.

PMID- 24102049
TI  - The role of rodents in the ecology of Ixodes ricinus and associated pathogens in
      Central and Eastern Europe.
AB  - Rodents comprise more species than any other mammal order. Most rodents are
      considered keystone species in their ecological communities, hence the survival
      of many other species in the ecosystem depend on them. From medical point of
      view, this is particularly important for rodent-dependent pathogens. In the
      particular case of tick-borne diseases, rodents are important as hosts for vector
      ticks and as reservoir hosts (Lyme borreliosis, human granulocytic anaplasmosis,
      Crimean-Congo hemorrhagic fever, Tick-borne relapsing fevers, tick-borne
      rickettsioses, babesiosis). Community and population ecology of rodents was shown
      to be correlated with disease ecology in the case of many tick-borne diseases. In
      Eastern Europe, several adult hard-tick species use rodents as their principal
      hosts: Ixodes apronophorus, I. crenulatus, I. laguri, I. redikorzevi, I.
      trianguliceps. However, the majority of ticks feeding on rodents are immature
      stages of ticks which as adults are parasitic on larger mammals. Larvae and
      nymphs of Ixodes ricinus, the most abundant and medically important tick from
      Europe, are commonly found on rodents. This is particularly important, as many
      rodents are synanthropic and, together with other micromammals and birds are
      often the only available natural hosts for ticks in urban environments. This work
      reviews the correlated ecology of rodents and I. ricinus. 

PMID- 24102050
TI  - Bioaccumulation experiments in mussels contaminated with the food-borne pathogen
      Arcobacter butzleri: preliminary data for risk assessment.
AB  - The aim of this study was to evaluate, at a laboratory scale, the ability of this
      microorganism to grow in seawater and bioaccumulate in mussels (Mytilus
      galloprovincialis) maintained in constantly aerated tanks, containing twenty
      litres of artificial seawater. Three concentrations of A. butzleri LMG 10828(T)
      were tested (about 5 * 106 CFU/mL, 5 * 104 CFU/mL, and 5 * 102 CFU/mL). Following
      contamination, enumeration of A. butzleri was performed from water and mussels
      each day, for up to 96 h. Three contamination experiments with artificial
      seawater in absence of mussels were also performed in the same manner. In the
      experiments with mussels, A. butzleri declined in water of approximately 1 log
      every 24 h from the contamination. In artificial seawater without mussels the
      concentration of A. butzleri remained on the same logarithmic level in the first
      48 h and then decreased of about 1 log every 24 hours. In mussels, the
      concentration was approximately 2 log lower than the exposition level after 24 h
      from the contamination, and then it decreased exponentially of 1 log every 24 h.
      Our findings suggest that in the experimental conditions tested A. butzleri is
      neither able to effectively grow in seawater nor bioaccumulate in mussels, at
      least in the free and cultivable form.

PMID- 24102051
TI  - Different levels in orexin concentrations and risk factors associated with higher
      orexin levels: comparison between detoxified opiate and methamphetamine addicts
      in 5 Chinese cities.
AB  - This study sought to explore the degree of orexin levels in Chinese opiate and
      methamphetamine addicts and the differences between them. The cross-sectional
      study was conducted among detoxified drug addicts from Mandatory Detoxification
      Center (MDC) in five Chinese cities. Orexin levels were assayed with
      radioimmunoassay (RIA). Mann-Whitney U test and Kruskal-Wallis test were used to
      detect differences across groups, and logistic regression was used to explore the
      association between orexin levels and characteristics of demographic and drug
      abuse. Between November 2009 and January 2011, 285 opiates addicts, 112
      methamphetamine addicts, and 79 healthy controls were enrolled. At drug
      withdrawal period, both opiate and methamphetamine addicts had lower median
      orexin levels than controls, and median orexin levels in opiate addicts were
      higher than those in methamphetamine addicts (all above P < 0.05). Adjusted odds
      of the above median concentration of orexin were higher for injection than
      "chasing the dragon" (AOR = 3.1, 95% CI = 1.2-7.9). No significant factors
      associated with orexin levels of methamphetamine addicts were found. Development
      of intervention method on orexin system by different administration routes
      especially for injected opiate addicts at detoxification phase may be significant
      and was welcome. 

PMID- 24102052
TI  - Incidence and risk factors of early delirium after cardiac surgery.
AB  - INTRODUCTION: The aim of our study was to identify the incidence and risk factors
      of delirium after cardiac surgery implementing Intensive Care Delirium Screening
      Checklist (ICDSC). MATERIAL AND METHODS: 87 patients, undergoing cardiac surgery
      at Vilnius University hospital, were prospectively monitored for postoperative
      delirium development, during intensive care unit stay. RESULTS: The incidence of
      postoperative delirium was 13.30%. No statistically relevant preoperative
      predictors of delirium were found. The duration of surgery was significantly
      longer in delirium group (4.51 +/- 1.15 versus 3.76 +/- 0.97 hours, P = 0.017).
      Patients in delirium group more often had blood product transfusions (1.50 (+/-
      1.57) versus 0.49 (+/- 0.91) P = 0.003) and had a higher incidence of low cardiac
      output syndrome (33.30% versus 3.00%, P = 0.004); they were significantly longer
      mechanically ventilated (24.31 +/- 28.35 versus 8.78 +/- 4.77 (P < 0.001)) hours
      (OR = 1.15 (1.02-1.28)) and had twice longer ICU stay (5.00 +/- 2.22 versus 2.60
      +/- 1.10 (P < 0.001)) days (OR = 1.91 (1.22-3.00)). CONCLUSIONS: The incidence of
      delirium after cardiac surgery was 13.3%. Independent predictors of delirium were
      duration of postoperative mechanical ventilation and intensive care unit stay.

PMID- 24102053
TI  - Common variant of FTO gene, rs9939609, and obesity in Pakistani females.
AB  - Numerous studies confirmed the association of FTO (fat mass and obesity
      associated gene) common variant, rs9939609, with obesity in European populations.
      However, studies in Asian populations revealed conflicting results. We examined
      the association of rs9939609 variant of FTO gene with obesity and obesity-related
      anthropometric and metabolic parameters in Pakistani population. Body weight,
      height, waist circumference, hip circumference, and blood pressure (BP) were
      measured. BMI and waist-to-hip ratio (WHR) were calculated. Levels of fasting
      blood glucose (FBG), insulin, leptin, and leptin receptors were measured by
      enzyme linked immunosorbent assay (ELISA), and homeostasis model assessment of
      insulin resistance (HOMA-IR) was calculated. The results showed association of
      FTO gene, rs9939609, with obesity in females (>18 years of age). FTO minor allele
      increased the risk of obesity by 2.8 times (95% CI = 1.3-6.0) in females. This
      allele showed association with body weight, BMI, waist circumference, hip
      circumference, WHR, BP, plasma FBG levels, HOMA-IR, plasma insulin levels, and
      plasma leptin levels. In conclusion, FTO gene, rs9939609, is associated with BMI
      and risk of obesity in adult Pakistani females. Association of rs9939609 variant
      with higher FBG, plasma insulin, and leptin levels indicates that this
      polymorphism may disturb the metabolism in adult females and predispose them to
      obesity and type 2 diabetes. However, the above-mentioned findings were not seen
      in children or males. 

PMID- 24102054
TI  - CD133 expression in normal skin and in epithelial cutaneous tumors.
AB  - BACKGROUND: Expression of human CD133 (human prominin-1) in cancer cells has been
      postulated to be a marker of stemness and is considered as a putative marker of
      cancer stem cells (CSCs). We designed a study to describe the expression pattern
      of CD133 in normal skin and in epithelial cutaneous neoplasms. METHODS: The CD133
      immunohistochemical expression of forty-three eccrine and apocrine tumors was
      compared to that observed in other epithelial tumors of the skin. In addition,
      flow cytometry was used to detect the CD133 expression of four epithelial skin
      neoplasms, including one porocarcinoma. RESULTS: CD133 immunoreactivity at the
      apical or at the apicolateral surface of cells forming glandular structures was
      observed. Cells from solid areas of benign or malignant tumors were not stained.
      The porocarcinoma derived culture cells showed a 22% of CD133 positive cells
      using flow cytometry, while squamous cell carcinoma cultures contained less than
      0.1%. CONCLUSIONS: These observations indicate that CD133 is a specific marker of
      glandular differentiation that could be included in the diagnostic panel of
      cutaneous tumors with possible eccrine or apocrine differentiation. However, the
      use of CD133 expression as a marker of CSCs should be interpreted with caution in
      experiments of skin.

PMID- 24102056
TI  - Heart rate variability is associated with survival in patients with brain
      metastasis: a preliminary report.
AB  - Impaired heart rate variability (HRV) has been demonstrated as a negative
      survival prognosticator in various diseases. We conducted this prospective study
      to evaluate how HRV affects brain metastasis (BM) patients. Fifty-one BM patients
      who had not undergone previous brain operation or radiotherapy (RT) were
      recruited from January 2010 to July 2012, and 40 patients were included in the
      final analysis. A 5-minute electrocardiogram was obtained before whole brain
      radiotherapy. Time domain indices of HRV were compared with other clinical
      factors on overall survival (OS). In the univariate analysis, Karnofsky
      performance status (KPS) <70 (P = 0.002) and standard deviation of the normal-to
      normal interval (SDNN) <10 ms (P = 0.004) significantly predict poor survival.
      The multivariate analysis revealed that KPS <70 and SDNN <10 ms were independent
      negative prognosticators for survival in BM patients with hazard ratios of 2.657
      and 2.204, respectively. In conclusion, HRV is associated with survival and may
      be a novel prognostic factor for BM patients. 

PMID- 24102055
TI  - Effectiveness of green tea in a randomized human cohort: relevance to diabetes
      and its complications.
AB  - Epidemiological studies have argued that green tea could mitigate diabetes and
      its complications. This study investigated the phytophenolic profile of Mauritian
      green tea and its antioxidant propensity. The effect of green tea on the risk
      factors: waist-hip ratio, glucose level, arterial pressure, antioxidant status,
      and alanine aminotransferase (ALT) in prediabetics was assessed. The experimental
      group consumed 3 cups of green tea daily for 14 weeks followed by a 2-week
      washout period. The control group followed a water regimen. Green tea contained
      high level of phenolics related to its antioxidant power. Green tea suppressed
      waist-hip ratio of women from a significant increase and suppressed mean arterial
      pressure of men and women from a significant decrease after week 14. It reduced
      ALT level in women by 13.0% (P < 0.1) while increasing the antioxidant potential
      of men and women sera by 2.7% (P < 0.1) and 5.1% (P < 0.1). The study timescale
      may have been too short to enable demonstration of effects on fasting plasma
      glucose and HbA1c outcomes. Green tea regimen could form part of a healthy
      lifestyle that might ameliorate features of metabolic syndrome and subsequent
      risks for diabetes and its complications. This trial is registered with
      ClinicalTrials.gov NCT01248143. 

PMID- 24102057
TI  - Pharmacological treatment for hepatopulmonary syndrome.
AB  - AIM: Hepatopulmonary syndrome is a pulmonary dysfunction in the context of liver
      cirrhosis characterized by arterial deoxygenation. Affected patients have
      increased morbidity and mortality, and many of them expire before undergoing
      liver transplantation. Therefore, finding medical therapy as a bridge to
      transplantation or as a final treatment is necessary. In this study, we aimed to
      review the current literature about pharmacological options available for
      treatment of hepatopulmonary syndrome. METHODS: A PubMED and Scopus search was
      conducted in January 2013 on the English literature published in any time period
      to find human and animal studies reporting pharmacological therapy of
      hepatopulmonary syndrome. RESULTS: Out of 451 studies, 29 relevant articles were
      included. The number of patients, type, dose, duration, and mechanism of drugs in
      these studies was extracted and summarized separately. Most of pharmacologic
      agents act through inhibition of nitric oxide synthase and reduction in nitric
      oxide production, inactivation of endothelin-1, and treatment of bacterial
      translocation and pulmonary angiogenesis. CONCLUSION: Several drugs have been
      applied for the treatment of HPS with conflicting results. However, no large
      randomized trial has been conducted probably due to low number of patients.
      Multicentered clinical trials are necessary to investigate these drugs.

PMID- 24102058
TI  - IgE sensitization to the nonspecific lipid-transfer protein Ara h 9 and peanut
      associated bronchospasm.
AB  - Allergen component analysis is now available in many laboratories. The aim of
      this study was to examine the possible association between peanut allergen IgE
      components and severity of clinical reactions in patients with a history of
      peanut allergy. Data and sera collected from 192 patients within the Manchester
      Allergy Research Database and Serum Bank were used in this retrospective study.
      Sensitization to peanut specific IgE and Ara h 1, 2, 3, and 8 peanut IgE
      components, as measured by fluoroenzyme immunoassay, was not associated with
      anaphylaxis. In contrast, sensitization to the lipid-transfer protein Ara h 9 was
      significantly more prevalent in patients with peanut-associated bronchospasm (26%
      versus 9% of patients), even after adjusting for potential confounding effects of
      age, gender, and severity of concomitant chronic atopic diseases. Patients who
      were sensitized to Ara h 9 were more likely to have ingested rather than just
      have had skin contact with peanut and have a more rapid onset of symptoms. These
      results are consistent with observations that sensitization to heat and protease
      resistant lipid-transfer protein components of hazelnut, grains, and fruit is
      predictive of anaphylaxis. 

PMID- 24102059
TI  - Low serum concentration of obestatin as a predictor of mortality in maintenance
      hemodialysis patients.
AB  - Obestatin, a proposed anorexigenic gut hormone, has been shown to have a number
      of beneficial cardiotropic effects in experimental studies. We hypothesized that
      obestatin alteration in hemodialysis patients may link to clinical outcomes. This
      cross-sectional study with prospective followup for almost 4 years was performed
      on 94 prevalent hemodialysis patients. Obestatin, leptin, proinflammatory
      cytokines (tumor necrosis factor-alpha [TNF-alpha], interleukin-6, and various
      nutritional markers were measured. Patients with low obestatin levels, defined as
      a level less than median, had a worse all-cause mortality and cardiovascular
      mortality. The crude all-cause (HR 2.23, 95% CI 1.17 to 4.24) and cardiovascular
      mortality hazard ratios (HR 4.03, 95% CI 1.27 to 12.76) in these patients
      continued to be significant after adjustment for various confounders for all
      cause mortality. Across the four obestatin-TNF-alpha categories, the group with
      low obestatin and high TNF-alpha (above median level) exhibited a worse outcome
      in both all-cause mortality and cardiovascular mortality. Clinical
      characteristics of patients in low obestatin high TNF-alpha group did not differ
      from other obestatin-TNF-alpha categorized groups. In summary, low serum
      obestatin concentration is an independent predictor of mortality in prevalent
      hemodialysis patients. Novel interactions were observed between obestatin and TNF
      alpha, which were associated with mortality risk, especially those due to
      cardiovascular causes.

PMID- 24102060
TI  - Arsenic, zinc, and aluminium removal from gold mine wastewater effluents and
      accumulation by submerged aquatic plants (Cabomba piauhyensis, Egeria densa, and
      Hydrilla verticillata).
AB  - The potential of three submerged aquatic plant species (Cabomba piauhyensis,
      Egeria densa, and Hydrilla verticillata) to be used for As, Al, and Zn
      phytoremediation was tested. The plants were exposed for 14 days under hydroponic
      conditions to mine waste water effluents in order to assess the suitability of
      the aquatic plants to remediate elevated multi-metals concentrations in mine
      waste water. The results show that the E. densa and H. verticillata are able to
      accumulate high amount of arsenic (95.2%) and zinc (93.7%) and resulted in a
      decrease of arsenic and zinc in the ambient water. On the other hand, C.
      piauhyensis shows remarkable aluminium accumulation in plant biomass (83.8%)
      compared to the other tested plants. The ability of these plants to accumulate
      the studied metals and survive throughout the experiment demonstrates the
      potential of these plants to remediate metal enriched water especially for mine
      drainage effluent. Among the three tested aquatic plants, H. verticillata was
      found to be the most applicable (84.5%) and suitable plant species to
      phytoremediate elevated metals and metalloid in mine related waste water. 

PMID- 24102061
TI  - The mode of inheritance of Scheuermann's disease.
AB  - The mode of Scheuermann's disease inheritance and its phenotypic traits in
      probands and their relatives were studied in 90 pedigrees (90 probands and 385
      relatives). The disorder was identified as a genetically related pathology
      inherited by autosomal dominant type, controlled by a mutant major gene, as a
      kyphotic deformity without signs of vertebral bodies' anomaly and torsion.
      Morphological and biochemical studies showed disturbance in the structure of
      vertebral growth plate anterior aspects at the level of deformity, defects in
      proliferation and differentiation of chondrocytes, and change in proteoglycan
      spectrum in cells and matrix. Twelve candidate genes were studied in chondrocytes
      isolated from vertebral growth plates of patients with Scheuermann's disease. The
      study results included disorder in the IHH gene expression and preservation of
      the expression of PAX1, two aggrecan isoforms, link protein, types I and II
      collagen, lumican, versican, growth hormone and growth factor receptor genes, and
      proliferation gene. Preservation of the SOX9 gene (transcription gene) probably
      indicates posttranscriptional genetic disorders. The study is under way. 

PMID- 24102062
TI  - Effect of restoration technique on stress distribution in roots with flared
      canals: an FEA study.
AB  - PURPOSE: The aim of this finite element analysis (FEA) study was to test the
      effect of different restorative techniques on stress distribution in roots with
      flared canals. MATERIALS AND METHODS: Five three-dimensional (3D) FEA models that
      simulated a maxillary incisor with excessive structure loss and flared root
      canals were created and restored with the following techniques/materials: 1) a
      prefabricated post: 2) one main and two accessory posts; 3) i-TFC post-core (Sun
      Medical); 4) the thickness of the root was increased by using composite resin and
      the root was then restored using a prefabricated post; 5) an anatomic post was
      created by using composite resin and a prefabricated glass-fiber post. Composite
      cores and ceramic crowns were created. A 300-N static load was applied at the
      center of the palatal surface of the tooth to calculate stress distributions.
      SolidWorks/Cosmosworks structural analysis programs were used for FEA analysis.
      RESULTS: The analysis of the von Mises and tensile stress values revealed that
      prefabricated post, accessory post, and i-TFC post systems showed similar stress
      distributions. They all showed high stress areas at the buccal side of the root
      (3.67 MPa) and in the cervical region of the root (> 3.67 MPa) as well as low
      stress accumulation within the post space (0 to 1 MPa). The anatomic post kept
      the stress within its body and directed less stress towards the remaining tooth
      structure. CONCLUSION: The creation of an anatomic post may save the remaining
      tooth structure in roots with flared canals by reducing the stress levels.

PMID- 24102063
TI  - Effects of adding barium-borosilicate glass to a simplified etch-and-rinse
      adhesive on radiopacity and selected properties.
AB  - PURPOSE: To evaluate the radiopacity, ultimate tensile strength (UTS),
      microhardness (KHN), degree of conversion (DC), water sorption (WS) and
      solubility (SL) of experimental adhesives. MATERIALS AND METHODS: Five
      experimental adhesives with different concentrations of barium-borosilicate oxide
      microfillers [0% (R0), 30% (R30), 40% (R40), 50% (R50), 60% (R60)] were
      formulated based on the adhesive system Ambar (FGM). The adhesive Adper Single
      Bond 2 (SB, 3M ESPE) was used as commercial reference. For the radiopacity (n =
      5), KHN (n = 5), WS (n = 10), and SL (n = 10) tests, adhesive disks were
      constructed (5.0 mm in diameter and 1.0 mm thick), while for UTS (n = 5),
      hourglass-shaped specimens with a cross-sectional area of 0.8 mm2 were used. The
      FTIR spectra of unpolymerized and polymerized adhesives were used to determine
      the DC. Data were submitted to a one-way ANOVA and Tukey's test (alpha = 0.05).
      RESULTS: All experimental adhesives showed radiopacity similar to enamel, except
      those of R0 and SB. Filler addition did not jeopardize the UTS, KHN, or WS of the
      filled adhesives in comparison with the unfilled version. Except for R40, filler
      addition reduced the SL. The filled adhesives showed lower DC when compared with
      R0, but the DC was similar or higher when compared with SB. CONCLUSIONS: The
      addition of barium-borosilicate glass up to 50% did not jeopardize the mechanical
      properties of the adhesive layer and seems to reduce its solubility.

PMID- 24102064
TI  - Influence of adhesive restorations on diffusion of H2O2 released from a bleaching
      agent and its toxic effects on pulp cells.
AB  - PURPOSE: To assess the influence of adhesive restorations on hydrogen peroxide
      (H2O2) diffusion through enamel and dentin and its cytotoxicity to pulp (MDPC-23)
      cells. MATERIALS AND METHODS: Sound and resin-restored enamel/dentin disks were
      stored in water for 24 h or 6 months and adapted to artificial pulp chambers.
      Bleaching gels with 20% or 35% H2O2 were applied to the enamel surface for 45
      min, and a culture medium in direct contact with the dentin surface (extract) was
      applied for 1 h to the MDPC-23 cells. Cell metabolism (MTT assay) and cell
      morphology (SEM) were assessed. The amount of H2O2 in the extracts was also
      quantified (peroxidase/leuco-crystal violet reaction). RESULTS: A significant
      reduction in cell metabolism was observed between the group bleached with the 35%
      gel and the control group (sound, nonbleached) (p < 0.05). The H2O2 diffusion was
      directly related to its concentration in the bleaching gel. The variables
      "presence of restoration" and "time of water storage" did not significantly
      influence H2O2 diffusion or cell metabolism for either of the bleaching gels (p >
      0.05). All bleached groups presented alterations in cell morphology related to
      the concentration of H2O2 in the bleaching gel. CONCLUSION: The reduction in cell
      metabolism and the changes in cell morphology were H2O2-concentration dependent,
      having no relationship with the presence of either new or aged adhesive
      restorations on teeth subjected to bleaching therapies.

PMID- 24102065
TI  - Measuring and modelling cell-to-cell variation in uptake of gold nanoparticles.
AB  - The cell-to-cell variation of gold nanoparticle (GNP) uptake is important for
      therapeutic applications. We directly counted the GNPs in hundreds of individual
      cells, and showed that the large variation from cell-to-cell could be directly
      modelled by assuming log-normal distributions of both cell mass and GNP rate of
      uptake. This was true for GNPs non-specifically bound to fetal bovine serum or
      conjugated to a cell penetrating peptide. Within a population of cells, GNP
      content varied naturally by a factor greater than 10 between individual cells. 

PMID- 24102066
TI  - Faujasites incorporated tissue engineering scaffolds for wound healing: in vitro
      and in vivo analysis.
AB  - Exploring the possibility of using inorganic faujasites in tissue engineering
      scaffolds is a prospective approach in regenerative medicine. Novel
      gelatin/hyaluronic acid (HA)/faujasite porous scaffolds with low surface energy
      were fabricated by lyophilization. The pore size of gelatin/HA scaffold was 50
      2000 MUm, whereas it was greatly reduced to 10-250 MUm after incorporation of
      2.4% (w/w) of faujasites in polymer matrix, GH(2.4%). Micro computed tomography
      analysis showed that the porosity of GH(2.4%) was 90.6%. The summative effect was
      ideal for growth of dermal fibroblasts and cellular attachment. XRD analysis
      revealed that the embedded faujasites maintained their crystallinity in the
      polymer matrix even though they interacted with the polymers as indicated by FT
      IR analysis. Coupling with effective reinforcement of faujasites, GH(2.4%)
      demonstrated compression modulus of 929 +/- 7 Pa and glass transition temperature
      of 31 +/- 0.05  degrees C. It exhibited controlled swelling and degradation,
      allowing sufficient space for tissue regrowth. The latter is further supported by
      capability of faujasites to provide efficient oxygen supply to fibroblast cells.
      GH(2.4%) showed a cell viability of 91 +/- 8% on NIH 3T3 fibroblast cell lines.
      The in vivo studies on Sprague-Dawley rats revealed its ability to enhance wound
      healing by accelerating re-epithelization and collagen deposition. These findings
      indicated its potential as excellent wound dressing material. 

PMID- 24102067
TI  - Data-mining for sulfur and fluorine: an evaluation of pharmaceuticals to reveal
      opportunities for drug design and discovery.
AB  - Among carbon, hydrogen, oxygen, and nitrogen, sulfur and fluorine are both
      leading constituents of the pharmaceuticals that comprise our medicinal history.
      In efforts to stimulate the minds of both the general public and expert
      scientist, statistics were collected from the trends associated with therapeutics
      spanning 12 disease categories (a total of 1969 drugs) from our new graphical
      montage compilation: disease focused pharmaceuticals posters. Each poster is a
      vibrant display of a collection of pharmaceuticals (including structural image,
      Food and Drug Administration (FDA) approval date, international nonproprietary
      name (INN), initial market name, and a color-coded subclass of function)
      organized chronologically and classified according to an association with a
      particular clinical indication. Specifically, the evolution and structural
      diversity of sulfur and the popular integration of fluorine into drugs introduced
      over the past 50 years are evaluated. The presented qualitative conclusions in
      this article aim to promote innovative insights into drug development. 

PMID- 24102068
TI  - Iranian nurses' experience with applying information from continuing education
      programs in clinical practice.
AB  - BACKGROUND: One goal of continuing education is to improve nurses' performance
      and the quality of patient care. However, in most cases, nurses do not use the
      information gained through continuing education in the clinical environment. This
      study was conducted to explore nurses' experiences with applying new knowledge
      obtained from these programs in clinical settings. METHODS: This study used
      qualitative content analysis. Data were gathered through interviews with
      participants. After the interviews were transcribed, a coding process was used
      and continued until categories and subcategories were developed. RESULTS: Five
      main categories emerged: (1) personal interest and self-confidence; (2)
      organizational structure and atmosphere; (3) professional nature; (4) opportunity
      to put education into practice; and (5) design of educational programs. Most of
      the nurses considered obligatory participation in these classes a way to gain
      annual educational upgrades. CONCLUSION: A considerable amount of the annual
      budget is allocated to continuing education. Therefore, the findings of this
      study, which described nurses' experience with applying what they learned through
      continuing education in clinical practice, can offer valuable information to help
      managers improve continuing education programs and the application of new
      knowledge in the clinical environment.

PMID- 24102069
TI  - Comparative study of notoungulate (Placentalia, Mammalia) bony labyrinths and new
      phylogenetically informative inner ear characters.
AB  - The phylogenetic relationships of notoungulates, an extinct group of
      predominantly South American herbivores, remain poorly resolved with respect to
      both other placental mammals and among one another. Most previous phylogenetic
      analyses of notoungulates have not included characters of the internal cranium,
      not least because few such features, including the bony labyrinth, have been
      described for members of the group. Here we describe the inner ears of the
      notoungulates Altitypotherium chucalensis (Mesotheriidae), Pachyrukhos moyani
      (Hegetotheriidae) and Cochilius sp. (Interatheriidae) based on reconstructions of
      bony labyrinths obtained from computed tomography imagery. Comparisons of the
      bony labyrinths of these taxa with the basally diverging notoungulate Notostylops
      murinus (Notostylopidae), an isolated petrosal from Itaborai, Brazil, referred to
      Notoungulata, and six therian outgroups, yielded an inner ear character matrix of
      25 potentially phylogenetically informative characters, 14 of them novel to this
      study. Two equivocally optimized character states potentially support a pairing
      of Mesotheriidae and Hegetotheriidae, whereas four others may be diagnostic of
      Notoungulata. Three additional characters are potentially informative for
      diagnosing more inclusive clades: one for crown Placentalia; another for a clade
      containing Kulbeckia, Zalambdalestes, and Placentalia; and a third for Eutheria
      (crown Placentalia plus stem taxa). Several other characters are apomorphic for
      at least one notoungulate in our study and are of potential interest for broader
      taxonomic sampling within Notoungulata to clarify currently enigmatic
      interrelationships. Measures of the semicircular canals were used to infer
      agility (e.g. capable of quick movements vs. lethargic movements) of these taxa.
      Agility scores calculated from these data generally corroborate interpretations
      based on postcranial remains of these or closely related species. We provide
      estimates of the low-frequency hearing limits in notoungulates based on the ratio
      of radii of the apical and basal turns of the cochlea. These limits range from 15
      Hz in Notostylops to 149 Hz in Pachyrukhos, values comparable to the Asian
      elephant (Elephas maximus) and the California sea lion (Zalophus californianus)
      when hearing in air, respectively.

PMID- 24102070
TI  - Preclinical evaluation of 4-[3,5-bis(2-chlorobenzylidene)-4-oxo-piperidine-1-yl]
      4-oxo-2-butenoic acid, in a mouse model of lung cancer xenograft.
AB  - BACKGROUND AND PURPOSE: 4-[3,5-Bis(2-chlorobenzylidene)-4-oxo-piperidine-1-yl]-4
      oxo-2-butenoic acid CLEFMA is a new anti-cancer molecule. Here, we investigated
      changes in apoptosis and inflammatory markers during CLEFMA-induced tumour
      suppression. EXPERIMENTAL APPROACH: Lung adenocarcinoma H441 and A549, and normal
      lung fibroblast CCL151 cell lines were used, along with a xenograft model of H441
      cells implanted in mice. Tumour tissues were analysed by immunoblotting,
      immunohistochemistry and/or biochemical assays. The ex vivo results were
      confirmed by performing selected assays in cultured cells. KEY RESULTS: CLEFMA
      induced cell death was associated with cleavage of caspases 3/9 and PARP. In
      vivo, CLEFMA treatment resulted in a dose-dependent suppression of tumour growth
      and (18) F-fluorodeoxyglucose uptake in tumours, along with a reduction in the
      expression of the proliferation marker Ki-67. In tumour tissue homogenates, the
      anti-apoptotic markers (cellular inhibitor of apoptosis protein-1(cIAP1), Bcl-xL,
      Bcl-2, and survivin) were inhibited and the pro-apoptotic Bax and BID were up
      regulated. Further, CLEFMA decreased translocation of phospho-p65-NF-kappaB into
      the nucleus. In vitro, it inhibited the DNA-binding and transcriptional activity
      of NF-kappaB. It also reduced the expression of COX-2 in tumours and
      significantly depressed serum TNF-alpha and IL-6 levels. These effects of CLEFMA
      were accompanied by a reduced transcription and/or translation of the invasion
      markers VEGF, MMP9, MMP10, Cyclin D1 and ICAM-1. CONCLUSIONS AND IMPLICATIONS:
      Overall, CLEFMA inhibited growth of lung cancer xenografts and this tumour
      suppression was associated with NF-kappaB-regulated anti-inflammatory and anti
      metastatic effects.

PMID- 24102071
TI  - New insights into metal interactions with the prion protein: EXAFS analysis and
      structure calculations of copper binding to a single octarepeat from the prion
      protein.
AB  - Copper coordination to the prion protein (PrP) has garnered considerable interest
      for almost 20 years, due in part to the possibility that this interaction may be
      part of the normal function of PrP. The most characterized form of copper binding
      to PrP has been Cu(2+) interaction with the conserved tandem repeats in the N
      terminal domain of PrP, termed the octarepeats, with many studies focusing on
      single and multiple repeats of PHGGGWGQ. Extended X-ray absorption fine structure
      (EXAFS) spectroscopy has been used in several previous instances to characterize
      the solution structure of Cu(2+) binding into the peptide backbone in the HGGG
      portion of the octarepeats. All previous EXAFS studies, however, have benefitted
      from crystallographic structure information for [Cu(II) (Ac-HGGGW-NH2)(-2H)] but
      have not conclusively demonstrated that the complex EXAFS spectrum represents the
      same coordination environment for Cu(2+) bound to the peptide backbone. Density
      functional structure calculations as well as full multiple scattering EXAFS curve
      fitting analysis are brought to bear on the predominant coordination mode for
      Cu(2+) with the Ac-PHGGGWGQ-NH2 peptide at physiological pH, under high Cu(2+)
      occupancy conditions. In addition to the structure calculations, which provide a
      thermodynamic link to structural information, methods are also presented for
      extensive deconvolution of the EXAFS spectrum. We demonstrate how the EXAFS data
      can be analyzed to extract the maximum structural information and arrive at a
      structural model that is significantly improved over previous EXAFS
      characterizations. The EXAFS spectrum for the chemically reduced form of copper
      binding to the Ac-PHGGGWGQ-NH2 peptide is presented, which is best modeled as a
      linear two-coordinate species with a single His imidazole ligand and a water
      molecule. The extent of in situ photoreduction of the copper center during
      standard data collection is also presented, and EXAFS curve fitting of the
      photoreduced species reveals an intermediate structure that is similar to the
      Cu(2+) form with reduced coordination number.

PMID- 24102072
TI  - Beneficial hemodynamic effects of prone positioning in patients with acute
      respiratory distress syndrome.
AB  - RATIONALE: The effects of prone positioning during acute respiratory distress
      syndrome on all the components of cardiac function have not been investigated
      under protective ventilation and maximal alveolar recruitment. OBJECTIVES: To
      investigate the hemodynamic effects of prone positioning. METHODS: We included 18
      patients with acute respiratory distress syndrome ventilated with protective
      ventilation and an end-expiratory positive pressure titrated to a plateau
      pressure of 28-30 cm H2O. Before and within 20 minutes of starting prone
      positioning, hemodynamic, respiratory, intraabdominal pressure, and
      echocardiographic data were collected. Before prone positioning, preload reserve
      was assessed by a passive leg raising test. MEASUREMENTS AND MAIN RESULTS: In all
      patients, prone positioning increased the ratio of arterial oxygen partial
      pressure over inspired oxygen fraction, the intraabdominal pressure, and the
      right and left cardiac preload. The pulmonary vascular resistance decreased along
      with the ratio of the right/left ventricular end-diastolic areas suggesting a
      decrease of the right ventricular afterload. In the nine patients with preload
      reserve, prone positioning significantly increased cardiac index (3.0 [2.3-3.5]
      to 3.6 [3.2-4.4] L/min/m(2)). In the remaining patients, cardiac index did not
      change despite a significant decrease in the pulmonary vascular resistance.
      CONCLUSIONS: In patients with acute respiratory distress syndrome under
      protective ventilation and maximal alveolar recruitment, prone positioning
      increased the cardiac index only in patients with preload reserve, emphasizing
      the important role of preload in the hemodynamic effects of prone positioning.

PMID- 24102073
TI  - The ecology of sexual conflict: background mortality can modulate the effects of
      male manipulation on female fitness.
AB  - Sexual and parental conflicts can arise because males benefit by inducing
      elevated reproductive effort in their mates. For females, the costs of such
      manipulation are often manifested later in life, and may therefore covary with
      female life expectancy. Here, I outline a simple female life-history model where
      female life expectancy reflects extrinsic mortality rate, and elevated
      reproductive effort causes accelerated senescence. Using this model, I show that
      variation in extrinsic mortality rate can modulate the magnitude and sign of
      fitness effects that male manipulation has on females. This result has several
      interesting implications. First, it suggests that the fitness effects of sexual
      interactions can depend on ecological factors, such as predation, that influence
      life expectancy. Second, if mortality risk is condition-dependent but
      reproductive effort is not fully optimized in relation to individual condition,
      then sexual conflict intensity may increase with individual condition, selecting
      for condition-dependent reproductive strategies. Third, if males vary in
      manipulativeness, then the fitness effects of mating with a given male phenotype
      may depend on both female condition and extrinsic mortality rate. Fourth, life
      span extension in the laboratory can lead to overestimation of sexual and
      parental conflicts. Life expectancy may therefore be a key factor in sexual
      coevolution. 

PMID- 24102074
TI  - Family intervention and health care costs for kansas medicaid patients with
      schizophrenia.
AB  - Despite a number of studies investigating the effect of pharmacotherapy on
      treatment costs for schizophrenia patients, there has been little attention given
      to the effect of family intervention. In this study, data from the Kansas
      Medicaid system were used to analyze healthcare costs for 164 schizophrenia
      patients who had participated in family intervention. Structural equation
      modeling was used to test two competing views of the role of family intervention
      in treatment. The results showed that a model including direct and indirect
      effects of family intervention provided a better fit to the data. Family
      intervention had a significant indirect effect on general medical costs (through
      other psychological treatment) that showed a savings of $586 for each unit
      increase in the provision of these services. In addition, the total indirect
      effects for family intervention showed a $580 savings for general medical costs
      and $796 for hospitalization costs (for each unit increase). 

PMID- 24102075
TI  - Fusobacterium nucleatum induces cytokine production through Toll-like-receptor
      independent mechanism.
AB  - AIM: To determine whether Fusobacterium nucleatum's ability to invade cells
      allows the bacteria to activate pro-inflammatory response through cytosolic
      pattern recognition receptors, independent of surface Toll-like receptors (TLRs).
      METHODOLOGY: HEK293T cells, which lack endogenous TLRs, and overexpressing
      dominant negative myeloid differentiation primary response gene 88 (MyD88DN)
      protein, were infected with F. nucleatum and the production of interleukin-8 (IL
      8) was determined. The necessity for intracellular invasion of the bacteria for
      cytokine production was also investigated by blocking bacterial invasion with
      cytochalasin D. The roles of NFKB and p38 mitogen-activated protein kinase (MAPK)
      and nucleotide-binding oligomerization domain-1 (NOD-1) signalling pathways in F.
      nucleatum-induced IL-8 secretion were determined. RESULTS: Fusobacterium
      nucleatum-infected HEK293T cells produced IL-8 independent of the MYD88
      signalling. This response was inhibited by preventing F. nucleatum invasion into
      HEK293T cells. p38 MAPK but not the NFKB signalling pathway was required for F.
      nucleatum-mediated IL-8 production. HEK293T cells expressed NOD-1 but not NOD-2.
      Yet, inhibition of NOD-1 signalling did not affect F. nucleatum-induced IL-8
      secretion. CONCLUSIONS: Fusobacterium nucleatum invasion led to cytokine
      production, which is mediated by the p38 MAPK signalling but independent of TLRs,
      NOD-1, NOD-2 and NFKB signalling.

PMID- 24102076
TI  - Influence of lumbar spine extension on vertical jump height during maximal squat
      jumping.
AB  - The purpose of this study was to determine the influence of lumbar spine
      extension and erector spinae muscle activation on vertical jump height during
      maximal squat jumping. Eight male athletes performed maximal squat jumps.
      Electromyograms of the erector spinae were recorded during these jumps. A
      simulation model of the musculoskeletal system was used to simulate maximal squat
      jumping with and without spine extension. The effect on vertical jump height of
      changing erector spinae strength was also tested through the simulated jumps.
      Concerning the participant jumps, the kinematics indicated a spine extension and
      erector spinae activation. Concerning the simulated jumps, vertical jump height
      was about 5.4 cm lower during squat jump without trunk extension compared to
      squat jump. These results were explained by greater total muscle work during
      squat jump, more especially by the erector spinae work (+119.5 J). The erector
      spinae may contribute to spine extension during maximal squat jumping. The
      simulated jumps confirmed this hypothesis showing that vertical jumping was
      decreased if this muscle was not taken into consideration in the model. Therefore
      it is concluded that the erector spinae should be considered as a trunk extensor,
      which enables to enhance total muscle work and consequently vertical jump height.

PMID- 24102077
TI  - Systemic allergic dermatitis caused by Apiaceae root vegetables.
AB  - BACKGROUND: Immediate hypersensitivity reactions to root vegetables of the
      Umbelliferae plant family (Apiaceae) is well known. Delayed-type hypersensitivity
      is rarely reported. OBJECTIVE: To report the first case of systemic contact
      dermatitis caused by root vegetables and some chemical implications. MATERIALS
      AND METHODS: Prick and patch testing were performed with fresh vegetables and
      selected allergens, and this was followed by high-performance liquid
      chromatography-mass spectrometry (MS)/MS analysis of the falcarinol syringe.
      RESULTS: The patient was contact-sensitive to celeriac, parsnip, and carrot, but
      tested negative to falcarinol. Subsequent analysis showed that the syringe
      contained falcarinol. CONCLUSION: The non-occupational sensitization resulting
      from both direct and systemic contact with Apiaceae root vegetables was
      apparently not caused by falcarinol.

PMID- 24102078
TI  - Characterization of drug resistance and virulotypes of Salmonella strains
      isolated from food and humans.
AB  - The virulence of bacteria can be evaluated through both phenotypic and molecular
      assays. We applied these techniques to 114 strains of Salmonella enterica subsp.
      enterica collected from July 2010 to June 2012. Salmonella strains were of human
      origin (71/114) or isolated from food (43/114). The strain set included only the
      three predominant Salmonella serovars isolated in Italy from humans (S.
      Enteritidis, S. Typhimurium, S. 4,[5],12:i:-). These strains were screened via
      polymerase chain reaction for 12 virulence factors (gipA, gtgB, sopE, sspH1,
      sspH2, sodC1, gtgE, spvC, pefA, mig5, rck, srgA), while antimicrobial sensitivity
      was evaluated through the Kirby-Bauer assay. Fifty-nine different virulence
      profiles were highlighted; the genes showing the highest homology were those
      related to the presence of prophages (gipA, gtgB, sopE, sspH1, sspH2, sodC1,
      gtgE), while the genes related to the presence of plasmids were less frequently
      detected (spvC, pefA, mig5, rck, srgA). The Salmonella serovars Typhimurium and
      4,[5],12:i:- were closely related in terms of both virulotyping and antibiotic
      resistance. S. Enteritidis showed higher antibiotic sensitivity and a higher
      prevalence of genes related to plasmids.

PMID- 24102079
TI  - Influence of temperature on acid-stress adaptation in Listeria monocytogenes.
AB  - Our findings show that temperature plays a significant role in the induction of
      acid-stress adaptation in Listeria monocytogenes, and two distinct patterns were
      observed: (1) Presence of sublethal acid at 37 degrees C or 22 degrees C
      significantly induced acid-stress adaptation; and (2) Presence of sublethal acid
      at 4 degrees C did not induce any acid-stress adaptation. Both patterns were
      confirmed by two experimental models: (1) L. monocytogenes cells were first grown
      at 37 degrees C and then exposed to sublethal acid at 37 degrees C, 22 degrees C,
      and 4 degrees C prior to lethal acid challenge; (2) Alternatively, L.
      monocytogenes cells were first grown at 4 degrees C for 20 days before pre
      exposure to sublethal acid and then challenged with lethal acid. Regardless of
      whether L. monocytogenes cells were simultaneously exposed with both cold stress
      and sublethal acid stress, or subjected to cold growth first before exposure to
      sublethal acid, no acid-stress adaptation was induced at 4 degrees C. We also
      found that acid-stress adaptation in L. monocytogenes did not occur in acidic
      whey at 4 degrees C. Bead beating treatment prior to mild acid pre-exposure at 4
      degrees C partially induced acid adaptation in L. monocytogenes. Our findings
      suggest that cold temperature can prevent the risk of acid-stress adaptation in
      L. monocytogenes.

PMID- 24102080
TI  - Evaluation of target sequences for the polymerase chain reaction-based detection
      of Salmonella in artificially contaminated beef.
AB  - Salmonella is a major cause of foodborne diseases worldwide, which has fueled the
      demand for the development and evaluation of sensitive, specific, and rapid
      detection methodologies, such as polymerase chain reaction (PCR). In this study,
      six primer pairs for the detection of Salmonella were evaluated by PCR with
      isolates of Salmonella spp. (115) and other bacteria (104). The primers designed
      for the sifB gene provided the best performance regarding specificity and
      sensitivity (100%). These primers were selected and used to develop a PCR assay
      for Salmonella detection during the enrichment steps of the conventional
      detection method in spiked beef samples. The enrichment steps were: buffered
      peptone water (BPW), Rappaport-Vassiliadis soya broth (RVS) and at the Muller
      Kauffmann tetrathionate novobiocin broth (MKTTn), after 18 h (BPW) and 24 h (RVS
      and MKTTn) of incubation. The initial concentrations of the Salmonella inocula
      were 101, 102, and 103 colony-forming units/25 g. The protocol was able to detect
      Salmonella at all concentrations in the enrichment steps, but not in the
      nonenriched samples. These results indicated that the proposed protocol was
      suitable to detect Salmonella in beef during the intermediate stages of the
      conventional isolation protocol, substantially reducing the time required to
      obtain the final results.

PMID- 24102081
TI  - Antimicrobial resistance and detection of the mecA gene besides enterotoxin
      encoding genes among coagulase-negative Staphylococci isolated from clam meat of
      Anomalocardia brasiliana.
AB  - The marine clam Anomalocardia brasiliana is a candidate as a sentinel animal to
      monitor the contamination levels of coliforms in shellfish-harvesting areas of
      Brazil's northeastern region. The aim of the present study was to search
      enterotoxin-encoding genes plus the mecA gene among coagulase-negative
      staphylococci (CNS) isolates from shellfish meats of A. brasiliana. The specimen
      clam (n=48; 40 clams per sample) was collected during low tide in the bay area of
      Mangue Seco from April through June 2009, and random samples of chilled and
      frozen shelled clam meat (n=33; 250 g per sample) were obtained from retail shops
      from January through March 2012. Seventy-nine CNS isolates were identified,
      including Staphylococcus xylosus, S. cohnii spp. urealyticus, S. sciuri, and S.
      lentus. A high percentage of isolates resistant to erythromycin (58.5%),
      penicillin (51.2%), and tetracycline (43.9%), and the fluoroquinolones
      levofloxacin (39%) and ciprofloxacin (34.1%) were recorded from those
      environmental samples. Isolates from retail shops were particularly resistant to
      oxacillin (55.3%) and penicillin (36.8%). All CNS resistant to oxacillin and/or
      cefoxitin were positive for the presence of the mecA gene, but phenotypically
      susceptible to vancomycin. Also, the enterotoxin-encoding genes seg and seh were
      detected through multiplex-polymerase chain reaction in 77.7% and 88.8% of the
      isolates from environmental samples, versus 90.5% and 100% of the isolates from
      retail shops, respectively. The data reveal the risk to public health due to
      consuming raw or undercooked shellfish containing enterotoxigenic plus
      methicillin-resistant CNS.

PMID- 24102082
TI  - Evaluation of virulence and antimicrobial resistance in Salmonella enterica
      serovar Enteritidis isolates from humans and chicken- and egg-associated sources.
AB  - Salmonella enterica serovar Enteritidis is a leading cause of salmonellosis
      throughout the world and is most commonly associated with the consumption of
      contaminated poultry and egg products. Salmonella Enteritidis has enhanced
      ability to colonize and persist in extraintestinal sites within chickens. In this
      study, 54 Salmonella Enteritidis isolates from human patients (n=28), retail
      chicken (n=9), broiler farms (n=9), and egg production facilities (n=8) were
      characterized by antimicrobial susceptibility testing, plasmid analysis, genetic
      relatedness using XbaI and AvrII pulsed-field gel electrophoresis (PFGE), and the
      presence of putative virulence genes. Nine isolates were evaluated for their
      abilities to invade and survive in intestinal epithelial and macrophage cell
      lines. Overall, 56% (n=30) of isolates were resistant to at least one
      antimicrobial agent tested, yet no isolates showed resistance to more than three
      antimicrobials. All isolates carried a common ~55-kb plasmid, with some strains
      containing additional plasmids ranging from 3 to 50 kb. PFGE analysis revealed
      five XbaI and AvrII clusters. There were significant overlaps in the PFGE
      patterns of the isolates from human, chicken, and egg houses. All isolates tested
      PCR positive for iacP, purR, ttrB, spi4H, rmbA, sopE, invA, sopB, spvB, pagC,
      msgA, spaN, orgA, tolC, and sifA, and negative for iss, virB4, and sipB. Of the
      isolates selected for virulence testing, those containing the iron acquisition
      genes, iutA, sitA, and iucA, and ~50-kb plasmids demonstrated among the highest
      levels of macrophage and epithelial cell invasion, which may indicate their
      importance in pathogenesis.

PMID- 24102083
TI  - Economic analysis of bevacizumab, cetuximab, and panitumumab with
      fluoropyrimidine-based chemotherapy in the first-line treatment of KRAS wild-type
      metastatic colorectal cancer (mCRC).
AB  - OBJECTIVE: Colorectal cancer (CRC) is the third most commonly diagnosed cancer in
      Canada (excluding non-melanoma skin cancers). Bevacizumab is a recombinant
      humanized monoclonal antibody that selectively binds to human vascular
      endothelial growth factor. A sub-study confirmed its effectiveness in KRAS wild
      type patients. Recent evidence has shown clinical benefit from anti-epidermal
      growth factor treatments cetuximab and panitumumab in these patients. The cost
      effectiveness, to the Canadian healthcare system, of fluoropyrimidine-based
      chemotherapy (FBC) in combination with bevacizumab, cetuximab, or panitumumab was
      assessed for first-line treatment of KRAS wild-type mCRC patients. METHODS: A
      Markov model was developed and calibrated to progression-free/overall survival,
      using separately reported trial survival and adverse event results for each
      comparator. Health-state resource utilization was derived from published data and
      oncologist input. Utilities and unit prices were obtained from published
      literature and standard Canadian sources. RESULTS: Results per patient are over a
      lifetime horizon, to a maximum of 10 years, with 5% annual discounting.
      Comparators are ordered by total cost and the incremental cost-effectiveness
      ratio (ICER) of each is determined against the previous non-dominated therapy.
      Compared to FBC alone, bevacizumab + FBC has an ICER of $131,600 per QALY gained.
      Compared to bevacizumab + FBC, panitumumab + FBC is dominated and cetuximab + FBC
      has an ICER of $3.8 million per QALY. In probabilistic sensitivity analysis,
      bevacizumab + FBC had ~100%, ~100%, and 98.9% probabilities of being more cost
      effective than both of the other combination treatments at thresholds of
      $50,000/QALY, $100,000/QALY, and $200,000/QALY, respectively. CONCLUSION: For
      first-line treatment of KRAS-WT mCRC, bevacizumab + FBC is associated with
      substantially lower costs as compared to panitumumab + FBC or cetuximab + FBC.
      Key limitations were that survival curves and adverse event rates were taken from
      separate clinical trials and that an indirect comparison was not included. Given
      these findings, bevacizumab is likely to offer the best value for money for this
      patient population.

PMID- 24102084
TI  - Effects of acidic deposition and soil acidification on sugar maple trees in the
      Adirondack Mountains, New York.
AB  - We documented the effects of acidic atmospheric deposition and soil acidification
      on the canopy health, basal area increment, and regeneration of sugar maple (SM)
      trees across the Adirondack region of New York State, in the northeastern United
      States, where SM are plentiful but not well studied and where widespread
      depletion of soil calcium (Ca) has been documented. Sugar maple is a dominant
      canopy species in the Adirondack Mountain ecoregion, and it has a high demand for
      Ca. Trees in this region growing on soils with poor acid-base chemistry (low
      exchangeable Ca and % base saturation [BS]) that receive relatively high levels
      of atmospheric sulfur and nitrogen deposition exhibited a near absence of SM
      seedling regeneration and lower crown vigor compared with study plots with
      relatively high exchangeable Ca and BS and lower levels of acidic deposition.
      Basal area increment averaged over the 20th century was correlated (p < 0.1) with
      acid-base chemistry of the Oa, A, and upper B soil horizons. A lack of Adirondack
      SM regeneration, reduced canopy condition, and possibly decreased basal area
      growth over recent decades are associated with low concentrations of nutrient
      base cations in this region that has undergone soil Ca depletion from acidic
      deposition. 

PMID- 24102085
TI  - Glycogen Synthase Kinase 3 influences cell motility and chemotaxis by regulating
      PI3K membrane localization in Dictyostelium.
AB  - Glycogen Synthase Kinase 3 (GSK3) is a multifunctional kinase involved in diverse
      cellular activities such as metabolism, differentiation, and morphogenesis.
      Recent studies showed that GSK3 in Dictyostelium affects chemotaxis via TorC2
      pathway and Daydreamer. Now we report that GSK3 affects PI3K membrane
      localization, of which the mechanism has remained to be fully understood in
      Dictyostelium. The membrane localization domain (LD) of Phosphatidylinositol-3
      kinase 1 (PI3K1) is phosphorylated on serine residues in a GSK3 dependent
      mechanism and PI3K1-LD exhibited biased membrane localization in gsk3(-) cells
      compared to the wild type cells. Furthermore, multiple GSK3-phosphorylation
      consensus sites exist in PI3K1-LD, of which phosphomimetic substitutions restored
      cAMP induced transient membrane localization of PI3K1-LD in gsk3(-) cells. Serine
      to alanine substitution mutants of PI3K1-LD, in contrast, displayed constitutive
      membrane localization in wild type cells. Biochemical analysis revealed that GSK3
      dependent serine phosphorylation of PI3K1-LD is constitutive during the course of
      cAMP stimulation. Together, these data suggest that GSK3 dependent serine
      phosphorylation is a prerequisite for chemoattractant cAMP induced PI3K membrane
      localization. 

PMID- 24102086
TI  - Dual thermoresponsive and pH-responsive self-assembled micellar nanogel for
      anticancer drug delivery.
AB  - In this article, we prepared a dual thermoresponsive and pH-responsive self
      assembled micellar nanogel for anticancer drug delivery by using a degradable pH
      responsive ketal derivative, mPEG2000-Isopropylideneglycerol (mPEG-IS, PI)
      polymer. The purpose of this study is to develop an injectable dual-responsive
      micellar nanogel system which has a sol-gel phase transition by the stimulation
      of body temperature with improved stability and biocompatibility as a controlled
      drug delivery carrier for cancer therapy. The pH-responsive PI was designed with
      pH-responsive ketal group as hydrophobic moieties and PEG group as hydrophilic
      moieties. The PI micelles encapsulated paclitaxel (PTX) was fabricated. Then, the
      PI micelles were formed in a thermo-nanogel. The micellar nanogel could improve
      the solubility and stability of PTX. The physiochemical properties of PI micelles
      and micellar nanogel were characterized. The results showed that dual-responsive
      micellar nanogel could carry out sol-gel transition at 37  degrees C. The PI
      polymer can spontaneously self-assemble into micellar structure with size of 100
      200 nm. The dual-responsive micellar nanogel could be degraded under lower pH
      condition. The test in vitro PTX release showed that dual-responsive micellar
      nanogel could release about 70% for 70 h under pH 5.0 while about 10% release at
      pH 7.4 and pH 9.0. The dual-responsive micellar nanogel was of lower cytotoxicity
      and suppressed tumor growth most efficiently. The micellar nanogel will be a new
      potential dual-responsive drug delivery system for cancer therapy.

PMID- 24102087
TI  - Novel techniques of preparing TEM samples for characterization of irradiation
      damage.
AB  - Focus ion beam preparation of transmission electron microscopy (TEM) samples has
      become increasingly popular due to the relative ease of extraction of TEM foils
      from specific locations within a larger sample. However the sputtering damage
      induced by Ga ion bombardment in focus ion beam means that traditional
      electropolishing may be a preferable method. First, we describe a special
      electropolishing method for the preparation of irregular TEM samples from ex
      service nuclear reactor components, spring-shaped spacers. This method has also
      been used to prepare samples from a nonirradiated component for a TEM in situ
      heavy ion irradiation study. Because the specimen size is small (0.7 * 0.7 * 3
      mm), a sandwich installation is adopted to obtain high quality polishing. Second,
      we describe some modifications to a conventional TEM cross-section sample
      preparation method that employs Ni electroplating. There are limitations to this
      method when preparing cross-section samples from either (1) metals which are
      difficult to activate for electroplating, or (2) a heavy ion irradiated foil with
      a very shallow damage layer close to the surface, which may be affected by the
      electroplating process. As a consequence, a novel technique for preparing cross
      section samples was developed and is described. 

PMID- 24102088
TI  - Ochratoxin A levels in blood serum of Czech women in the first trimester of
      pregnancy and its correspondence with dietary intake of the mycotoxin
      contaminant.
AB  - The mycotoxin ochratoxin A (OTA) can elicit a wide range of toxic properties
      including embryotoxicity and teratogenicity. OTA crosses the placenta at early
      gestation rather than in late gestation, maternal OTA exposure may represent a
      risk for the developing fetus. The study focuses on the assessment of OTA intake
      of pregnant women (aged 19-40 years) in the first trimester of pregnancy by means
      OTA levels in 100 blood serum samples by high-performance liquid chromotography
      with fluorescence detection (HPLC-FD) method and comparison with dietary OTA
      exposure in pregnant women. Of all, 96% tested serum samples were positive with
      values ranging from 0.1 to 0.35 ug/l with a mean value of 0.15 ug/l.

PMID- 24102089
TI  - Microcystins: measuring human exposure and the impact on human health.
AB  - CONTEXT: Freshwater cyanobacterial toxins, microcystins, may be a contributing
      factor to the development of hepatocellular cancer and colorectal cancer.
      OBJECTIVES: This review summarizes the toxicity data, exposure routes and the
      methodologies available to determine exposure to elucidate the relationship to
      liver and colorectal cancer. METHODS: Literature searches were conducted using
      Medline, PubMed and Web of Science. RESULTS: There is evidence of human
      poisonings resulting from exposure to microcystins, however current methods rely
      on targeted approaches only suitable for acute exposure. No methods exist for the
      determination of chronic exposure to microcystins. CONCLUSIONS: With the growing
      evidence of exposure to microcystins and the possible links to cancer, methods to
      measure medium to long-term human exposure are needed. The identification and
      validation of candidate biomarkers are key to undertaking urgently required
      epidemiological studies.

PMID- 24102090
TI  - Plasma and EBC microRNAs as early biomarkers of non-small-cell lung cancer.
AB  - Lung cancer is a major cause of death in Western countries. Current screening
      methods are invasive and still lead to a high percentage of false positives.
      There is, therefore, a need to find biomarkers that increase the probability of
      detecting lung cancer early. MicroRNAs (miRNAs) are stable molecules in blood
      plasma and exhaled breath condensate (EBC). We quantified miRNA-21 and miRNA-486
      expression from plasma and EBC samples from patients with a diagnosis of non
      small-cell lung cancer (NSCLC) and controls. miRNA-21 was significantly higher in
      plasma and in EBC of the NSCLC patients and miRNA-486 was significantly lower.
      This difference indicates a significantly improved diagnostic value, and suggests
      that these miRNAs could be clinically used as a first-line screening test in high
      risk subjects.

PMID- 24102091
TI  - The association between galectin-3 and occurrence of reinfarction early after
      first myocardial infarction treated invasively.
AB  - CONTEXT: Galectin-3, as a biomarker of inflammation and fibrosis, has been
      reported to be associated with coronary artery disease. OBJECTIVE: The study
      aimed to assess the relationship between galectin-3 levels and the occurrence of
      reinfarction early after myocardial infarction (MI). METHODS: The study included
      145 consecutive patients with first MI treated invasively. Serum galectin-3 was
      measured using VIDAS (bioMerieux, Marcy-l'Etoile, France). RESULTS: The
      independent predictors of reinfarction in our group were as follows: female
      gender, elevated hs-C-reactive protein and galectin-3 levels (measured both at
      discharge). CONCLUSIONS: Galectin-3 might be an additional useful biomarker in
      prediction for reinfarction early after first MI.

PMID- 24102092
TI  - Genetic variations of the FCER2 gene and asthma susceptibility in north Indian
      children: a case-control study.
AB  - CONTEXT AND OBJECTIVE: The findings showed that the low-affinity IgE receptor
      plays a pivotal role in allergic immune response and it is a pharmacogenetic
      predictor in asthma disease. This study aims to investigate the association of
      genetic variations: rs28364072 and rs7249320 with asthma and its severity in
      north Indian children. METHODS: Case-control-based genetic association study was
      performed among 550 children. RESULTS: Statistical analysis demonstrated
      significant association between asthma and genotypes frequency of both the SNPs.
      CONCLUSIONS: Our data indicate that the studied variations are strongly
      associated with asthma susceptibility and might be risk factor among north Indian
      asthmatic children.

PMID- 24102093
TI  - Pharmacological effects of Trigonella foenum-graecum L. in health and disease.
AB  - CONTEXT: The health benefits and medicinal properties of herbal food products are
      known since antiquity. Fenugreek [Trigonella foenum-graecum Linn. (Fabaceae)], a
      seed spice used to enhance flavor, color and texture of food, is employed for
      medicinal purposes in many traditional systems. A number of epidemiological
      studies and laboratory research have unraveled the biological actions of
      fenugreek. OBJECTIVE: Research on fenugreek in recent years has identified a
      number of health benefits and physiological attributes in both experimental
      animals as well as clinical trials in humans. In this study we have reviewed the
      available scientific literature on fenugreek. METHODS: This review article
      summarizes and reviews published experimental studies and scientific literature
      from the databases including PubMed, Google and local library searches. RESULTS:
      The information available in the literature on the health benefits and
      pharmaceutical effects of Trigonella accounts for its known medicinal properties
      and adds new therapeutic effects in newer indications. Besides its known
      medicinal properties such as carminative, gastric stimulant, antidiabetic and
      galactogogue (lactation-inducer) effects, newer research has identified
      hypocholesterolemic, antilipidemia, antioxidant, hepatoprotective, anti
      inflammatory, antibacterial, antifungal, antiulcer, antilithigenic,
      anticarcinogenic and other miscellaneous medicinal effects of fenugreek. Although
      most of these studies have used whole seed powder or different forms of extracts,
      some have identified active constituents from seeds and attributed them medicinal
      values for different indications. CONCLUSION: The resarch on Trigonella exhibits
      its health benefits and potential medicinal properties in various indications and
      has little or no side effects, suggesting its pharmaceutical, therapeutic and
      nutritional potential.

PMID- 24102094
TI  - Encapsulation of podophyllotoxin and etoposide in biodegradable poly-D,L-lactide
      nanoparticles improved their anticancer activity.
AB  - To improve the efficacy podophyllotoxin (PODO) and etoposide (ETOPO) were
      encapsulated in poly-d,l-lactide nanoparticles (PLA NPs). The size of synthesised
      PODO-loaded PLA NPs and ETOPO-loaded PLA NPs was 100 +/- 17 nm and 163 +/- 20 nm
      and their encapsulation efficiency was 17 and 48%, respectively. In vitro release
      studies showed initial burst release followed by slow and sustained release. In
      vitro cytotoxicity of synthesised NPs was assessed using A549 and CHO-K1 cells.
      Blank PLA NPs did not show any toxicity. While PODO-loaded PLA NPs showed higher
      in vitro cytotoxicity in comparison to ETOPO-loaded PLA NPs against both cell
      lines. Also, the cytotoxicity of both PODO-loaded PLA NPs and ETOPO-loaded PLA
      NPs was higher compared to pure drugs. Hence, this study documents the
      improvement in efficacy of these molecules upon encapsulation in PLA NPs and
      could be an important strategy for better therapeutics.

PMID- 24102095
TI  - Resolving the distribution-metabolism interplay of eight OATP substrates in the
      standard clearance assay with suspended human cryopreserved hepatocytes.
AB  - Uptake transporters may act to elevate the intrahepatic exposure of drugs,
      impacting the route and rate of elimination, as well as the drug-drug interaction
      potential. We have here extended the assessment of metabolic drug stability in a
      standard human hepatocyte incubation to allow for elucidation of the distribution
      metabolism interplay established for substrates of drug transporters. Cellular
      concentration-time profiles were obtained from incubations of eight known OATP
      substrates at 1 MUM, each for two different 10-donor batches of suspended
      cryopreserved human hepatocytes. The kinetic data sets were analyzed using a
      mechanistic mathematical model that allowed for separate estimation of active
      uptake, bidirectional diffusion, metabolism and nonspecific extracellular and
      intracellular binding. The range of intrinsic clearances attributed to active
      uptake, diffusion and metabolism of the test set spanned more than 2 orders of
      magnitude each, with median values of 18, 5.3, and 0.5 MUL/min/10(6) cells,
      respectively. This is to be compared with the values for the apparent clearance
      from the incubations, which only spanned 1 order of magnitude with a median of
      2.6 MUL/min/10(6) cells. The parameter estimates of the two pooled 10-donor
      hepatocyte batches investigated displayed only small differences in contrast to
      the variability associated with use of cells from individual donors reported in
      the literature. The active contribution to the total cellular uptake ranged from
      55% (glyburide) to 96% (rosuvastatin), with an unbound intra-to-extracellular
      concentration ratio at steady state of 2.1 and 17, respectively. Principal
      component analysis showed that the parameter estimates of the investigated
      compounds were largely influenced by lipophilicity. Active cellular uptake in
      hepatocytes was furthermore correlated to pure OATP1B1-mediated uptake as
      measured in a transfected cell system. The presented approach enables the
      assessment of the key pathways regulating hepatic disposition of transporter and
      enzyme substrates from one single, reproducible and generally accessible human in
      vitro system. 

PMID- 24102096
TI  - Association of oral health behaviors and status with depression: results from the
      Korean National Health and Nutrition Examination Survey, 2010.
AB  - OBJECTIVE: To examine the association of depression with oral health behaviors
      and oral health status in a large nationwide sample of Korean adults. METHODS:
      This study included 6,139 participants aged 19 years or older who participated in
      the fifth Korean National Health and Nutrition Examination Survey. Binary and
      polychotomous logistic regression analyses were used to estimate adjusted odds
      ratios (AORs) and 95 percent confidence intervals (CIs). RESULTS: Participants
      with lifetime depression (self-report of past or present depression) brushed
      their teeth less frequently (AOR = 1.30, 95 percent CI 1.03-1.65) and were more
      likely not to receive treatment when experiencing dental problems (AOR = 1.43, 95
      percent CI 1.23-1.66) than those without lifetime depression after adjusting for
      sociodemographic factors, gender, and age. After adjusting for significant oral
      health behaviors, current smoking status, and sociodemographic factors,
      participants with lifetime depression had poorer oral health status than those
      without this disorder: uncomfortable mastication (AOR = 1.25, 95 percent CI 1.05
      1.50), toothache (AOR = 1.18, 95 percent CI 1.01-1.39), temporomandibular joint
      symptoms (AOR = 1.41, 95 percent CI 1.08-1.85), and maxillary periodontal
      bleeding (AOR = 1.29, 95 percent CI 1.03-1.61 for the right side; AOR = 1.40, 95
      percent CI 1.13-1.74 for the left side). CONCLUSION: Depression was significantly
      associated with oral health status, even after adjusting for the impact of oral
      health behaviors in Korean adults. Thus, our findings suggest the necessity of
      further investigation to detect underlying mechanisms in the relationship between
      depression and oral health that are not mediated by oral health behavior.

PMID- 24102097
TI  - Visualization of sarcoid choroidal granuloma by enhanced depth imaging optical
      coherence tomography.
AB  - PURPOSE: To report, in vivo, on the quasi-histologic characteristics of a sarcoid
      choroidal granuloma as visualized by Enhanced Depth Imaging Spectral Domain
      Optical Coherence Tomography (EDI SD-OCT). METHODS: A 49 year-old woman showing a
      choroidal granuloma secondary to sarcoidosis was imaged by EDI OCT. RESULT: On
      EDI SD-OCT examination, sarcoid choroidal granuloma appears as a localized
      hyporeflectivechoroidalthickening. Two weeks after systemic corticosteroids, the
      thickness of the granuloma decreased from 568 MUm to 356 MUm. Five months later,
      it reached 274 MUm, and after eleven months, it decreased to 150 MUm. CONCLUSION:
      EDI SD-OCT allows direct visualization of choroidal granuloma secondary to
      sarcoidosis and evaluation of lesion regression after treatment.

PMID- 24102099
TI  - Cerebroprotective action of angiotensin peptides in stroke.
AB  - The goal of the present review is to examine the evidence for beneficial actions
      of manipulation of the RAS (renin-angiotensin system) in stroke, with particular
      focus on Ang-(1-7) [angiotensin-(1-7)] and its receptor Mas. The RAS appears to
      be highly involved in the multifactorial pathophysiology of stroke. Blocking the
      effects of AngII (angiotensin II) at AT1R (AngII type 1 receptor), through the
      use of commonly prescribed ACE (angiotensin-converting enzyme) inhibitors or AT1R
      blockers, has been shown to have therapeutic effects in both ischaemic and
      haemorrhagic stroke. In contrast with the deleterious actions of over activation
      of AT1R by AngII, stimulation of AT2Rs (AngII type 2 receptors) in the brain has
      been demonstrated to elicit beneficial effects in stroke. Likewise, the ACE2/Ang
      (1-7)/Mas axis of the RAS has been shown to have therapeutic effects in stroke
      when activated, countering the effects of the ACE/AngII/AT1R axis. Studies have
      demonstrated that activating this axis in the brain elicits beneficial cerebral
      effects in rat models of ischaemic stroke, and we have also demonstrated the
      cerebroprotective potential of this axis in haemorrhagic stroke using stroke
      prone spontaneously hypertensive rats and collagenase-induced striatal
      haemorrhage. The mechanism of cerebroprotection elicited by ACE2/Ang-(1-7)/Mas
      activation includes anti-inflammatory effects within the brain parenchyma. The
      major hurdle to overcome in translating these results to humans is devising
      strategies to activate the ACE2/Ang-(1-7)/Mas cerebroprotective axis using post
      stroke treatments that can be administered non-invasively. 

PMID- 24102100
TI  - Assembly of surface-confined homochiral helicates: chiral discrimination of DOPA
      and unidirectional charge transfer.
AB  - Surface-confined double-helical polymers are generated by dynamic covalent
      assembly with preservation of chirality, metal coordination environment, and
      oxidation state of the precursor complexes. This one-step procedure involves both
      in solution and solution-to-surface assembly and resulted in chiral interfaces
      where pairs of ligands are wrapped around arrays of metal ions. In-plane XRD
      experiments revealed the formation of a highly ordered structure along the
      substrate surface. The chirality of the surfaces is expressed by the selective
      recognition of 3,4-dihydroxyphenylalanine (DOPA). The CD measurements show a
      response of the Delta-polymer-modified quartz substrates toward D-DOPA, whereas
      no change was observed after treatment with L-DOPA. These coordination-based
      interfaces assembled on metal-oxide substrates in combination with a redox-probe,
      [Os(bpy)3](PF6)2, in solution can resemble the behavior of a rectifier.

PMID- 24102101
TI  - Monitoring activities of daily living of the elderly and the potential for its
      use in telecare and telehealth: a review.
AB  - OBJECTIVE: This review was designed to determine whether telemonitoring
      activities of daily living (ADL) of elderly people can improve quality of life
      and be beneficial to their healthcare. MATERIALS AND METHODS: Electronic
      databases were searched for studies that monitored ADL of elderly people and
      preferably measured some clinical outcomes such as ability to predict key events
      that require intervention and for studies that assessed perception of elderly
      people of such telemonitoring systems. The articles were reviewed and assessed
      independently by two reviewers. RESULTS: One hundred seventy-five unique studies
      were found. Sixty-seven of these were identified for potential inclusion, and 25
      studies were finally included. Study characteristics, parameters monitored,
      outcomes, and problems encountered were summarized and discussed. The main focus
      was on the potential benefits of ADL monitoring on the care of elderly people.
      CONCLUSIONS: Although most studies reported on technical improvements in methods
      for detecting changes in ADL, few, if any, determined the benefits to the patient
      of telemonitoring for changes in ADL or correlation with any physiological
      changes. We propose sensor and system characteristics for improved user
      acceptance and deployment in a large-scale care plan. We present areas requiring
      further investigation.

PMID- 24102098
TI  - MicroRNAs in the onset and development of cardiovascular disease.
AB  - Physiological and pathological roles for small non-encoding miRNAs (microRNAs) in
      the cardiovascular system have recently emerged and are now widely studied. The
      discovery of widespread functions of miRNAs has increased the complexity of gene
      regulatory processes and networks in both the cardiovascular system and
      cardiovascular diseases. Indeed, it has recently been shown that miRNAs are
      implicated in the regulation of many of the steps leading to the development of
      cardiovascular disease. These findings represent novel aspects in miRNA biology
      and, therefore, our understanding of the role of these miRNAs during the
      pathogenesis of cardiovascular disease is critical for the development of novel
      therapies and diagnostic interventions. The present review will focus on
      understanding how miRNAs are involved in the onset and development of
      cardiovascular diseases. 

PMID- 24102102
TI  - Comparing the effectiveness of telemedicine and traditional surveillance in
      providing diabetic retinopathy screening examinations: a randomized controlled
      trial.
AB  - OBJECTIVE: To determine the effectiveness of telemedicine for providing diabetic
      retinopathy screening examinations compared with the effectiveness of traditional
      surveillance in community health clinics with a high proportion of minorities,
      including American Indian/Alaska Natives. SUBJECTS AND METHODS: We conducted a
      multicenter, randomized controlled trial and assigned diabetic participants to
      one of two groups: (1) telemedicine with a nonmydriatic camera or (2) traditional
      surveillance with an eye care provider. For those receiving telemedicine, the
      criteria for requiring follow-up with an eye care provider were (1) moderate
      nonproliferative diabetic retinopathy or higher, (2) presence of clinically
      significant macular edema, or (3) "unable to grade" result for diabetic
      retinopathy or macular edema. RESULTS: The telemedicine group (n=296) was more
      likely to receive a diabetic retinopathy screening examination within the first
      year of enrollment compared with the traditional surveillance group (n=271) (94%
      versus 56%, p<0.001). The overall prevalence of diabetic retinopathy at baseline
      was 21.4%, and macular edema was present in 1.4% of participants. In the
      telemedicine group, 20.5% would require further evaluation with an eye care
      provider, and 86% of these referrals were because of poor-quality digital images.
      CONCLUSIONS: Telemedicine using nonmydriatic cameras increased the proportion of
      participants who obtained diabetic retinopathy screening examinations, and most
      did not require follow-up with an eye care provider. Telemedicine may be a more
      effective way to screen patients for diabetic retinopathy and to triage further
      evaluation with an eye care provider. Methods to decrease poor quality imaging
      would improve the effectiveness of telemedicine for diabetic retinopathy
      screening examinations.

PMID- 24102103
TI  - Potential benefits to staff from humor therapy with nursing home residents.
AB  - Life in residential care can be challenging for residents and staff. Bringing
      humor into this setting may benefit residents, creating a more productive,
      enjoyable work environment for staff. The potential effect of exposure to humor
      therapy on staff, both as active and incidental participants, as part of a
      randomized controlled trial of the effect of humor therapy for aged care
      residents was investigated in the Sydney Multisite Intervention of LaughterBosses
      and ElderClowns (SMILE). The intervention involved a humor program with
      professional performers (ElderClowns) and trained facility staff (LaughterBosses)
      for a minimum of nine 2-hour sessions over 12 weeks. Methods included a staff
      survey at three time points, interviews with LaughterBosses, and a satisfaction
      rating by facility managers. There were significant positive findings for some
      staff subgroups, including assistants in nursing/personal care assistants and
      staff older than 45. LaughterBoss interviews and intervention group manager
      ratings of staff work enthusiasm were positive.

PMID- 24102104
TI  - Medication reconciliation: reducing risk for medication misadventure during
      transition from hospital to assisted living.
AB  - The discharge of older adults from hospital to home has been associated with poor
      outcomes. It is well documented that performing medication reconciliation at
      every transition point is critical to ensuring patient safety, preventing
      unnecessary rehospitalizations, and reducing the risk for medication
      misadventures. However, the medication reconciliation process is not well
      executed in numerous institutions and possibly not at all in many assisted living
      facilities (ALFs). Thus, the purpose of this study was to examine medication
      discrepancies that occur as a result of transitioning from hospitals to ALFs and
      to explore the role of nurses regarding medication reconciliation in ALFs. A
      comparison of medication records for 80 residents ages 65 and older revealed that
      86.2% of resident records had at least one medication discrepancy. These results
      represent an opportunity for nurses to be involved with post-acute care
      communication and medication reconciliation to improve safe transitions for
      residents in ALFs.

PMID- 24102105
TI  - The novel allele HLA-C*03:04:36 identified by sequence-based typing.
AB  - The new allele, HLA-C*03:04:36, differs from C*03:04:01:01 by one nucleotide
      substitution at codon 207 (GGC->GGT). 

PMID- 24102107
TI  - A chemometric approach for the sensitization procedure of ZnO flowerlike
      microstructures for dye-sensitized solar cells.
AB  - In this paper, a methodology for the streamlining of the sensitization procedure
      of flowerlike ZnO nanostructures for dye-sensitized solar cells (DSCs) is
      reported. The sensitization of ZnO surface with ruthenium-based complexes is a
      particularly critical process, since one has to minimize the dissolution of
      surface Zn atoms by the protons released from the dye molecules, leading to the
      formation of Zn(2+)/dye complexes. The fine-tuning of the experimental
      parameters, such as the dye loading time, the dye concentration, and the pH of
      the sensitizing solution, performed through a multivariate optimization by means
      of a chemometric approach, is here reported. The dye loading procedure was
      optimized using ZnO microparticles with nanostructured protrusions, synthesized
      by a simple and low-cost hydrothermal process. Mild reaction conditions were
      used, and wurtzite-like crystalline structure with a relatively high surface area
      was obtained once the reaction process was completed. After dispersion of ZnO
      flowerlike particles in an acetic acid-based solution, a 14 MUm-thick ZnO layer
      acting as DSC photoanode was fabricated. The optimized sensitization procedure
      allowed minimizing the instability of ZnO surface in contact with acidic dyes,
      avoiding the formation of molecular agglomerates unable to inject electrons in
      the ZnO conduction band, achieving good results in the photoconversion
      efficiency. Moreover, the photoharvesting properties were further enhanced by
      adding N-methylbenzimidazole into the iodine-based liquid electrolyte. Such an
      additive was proposed here for the first time in combination with a ZnO
      photoelectrode, helping to reduce an undesired recombination between the
      photoinjected electrons and the oxidized redox mediator. 

PMID- 24102108
TI  - Reply to the commentaries: Of course, we do not yet know what it is all about,
      but functional contextualism is a good place to start.
AB  - In this reply to the commentaries, we note several points of disagreement with
      Johnson and Greenman on theoretical and empirical grounds. We are particularly
      surprised by their assumption that attachment has already been established as the
      key mechanism of change in couple therapy, as our present findings do not support
      this idea. We also elaborate on Gurman's functional contextualist views and
      describe why IBCT may be a particularly helpful model for training new couple
      therapists in a contextualist way. 

PMID- 24102106
TI  - The role of ATP-sensitive potassium channels in cellular function and protection
      in the cardiovascular system.
AB  - ATP-sensitive potassium channels (K(ATP)) are widely distributed and present in a
      number of tissues including muscle, pancreatic beta cells and the brain. Their
      activity is regulated by adenine nucleotides, characteristically being activated
      by falling ATP and rising ADP levels. Thus, they link cellular metabolism with
      membrane excitability. Recent studies using genetically modified mice and genomic
      studies in patients have implicated K(ATP) channels in a number of physiological
      and pathological processes. In this review, we focus on their role in cellular
      function and protection particularly in the cardiovascular system.

PMID- 24102109
TI  - Impact of fluoroscopy unit on the accuracy of a magnet-based electroanatomic
      mapping and navigation system: an in vitro and in vivo validation study.
AB  - INTRODUCTION: During mapping and ablation procedures, the movement of large
      ferromagnetic items (i.e., fluoroscopic equipment) introduce heterogeneities in
      the electromagnetic field, which may affect the accuracy of electromagnet-based
      navigation. We aimed to assess the impact of common periprocedural fluoroscopic
      equipment movement on the accuracy of an electromagnet-based navigation system.
      METHODS AND RESULTS: The impact of fluoroscopic equipment movement on the
      accuracy of the Carto(r) 3 System (Biosense Webster, Inc., Diamond Bar, CA, USA)
      was assessed both in vitro (n = 20 patients, phantom model) and in vivo (n = 18
      patients). Location recordings were obtained with unchanged catheter position for
      fluoroscopic equipment rotational movements (RMs) and maximal to closest distance
      (MD to CD) to phantom/patient. The effects of both single- and biplane
      fluoroscopy were assessed. In vitro, the movement of fluoroscopic equipment
      resulted in an average catheter location estimation error of 0.8 mm
      (interquartile range 0.3-1.3). The maximal location estimation errors with MD to
      CD movement and RM were 2.3 mm and 1.3 mm, respectively. Changing from single
      plane to biplane setup resulted in an average location estimation change of 1.5
      mm (maximum 2.1). Larger location changes were observed in vivo (2.9 mm vs 0.8
      mm, P < 0.0001) with 28.7% of these exceeded 4 mm versus none of the in vitro
      measurements (P < 0.0001). CONCLUSION: Although fluoroscopy manipulation affected
      the accuracy of the Carto(r) 3 System, the in vitro data suggest that these
      inaccuracies are likely of limited clinical consequences. The larger in vivo
      inaccuracies are most likely due to nonferromagnetic interferences, such as
      respiratory or cardiac movements.

PMID- 24102110
TI  - When and where does mortality occur in migratory birds? Direct evidence from long
      term satellite tracking of raptors.
AB  - Information about when and where animals die is important to understand
      population regulation. In migratory animals, mortality might occur not only
      during the stationary periods (e.g. breeding and wintering) but also during the
      migration seasons. However, the relative importance of population limiting
      factors during different periods of the year remains poorly understood, and
      previous studies mainly relied on indirect evidence. Here, we provide direct
      evidence about when and where migrants die by identifying cases of confirmed and
      probable deaths in three species of long-distance migratory raptors tracked by
      satellite telemetry. We show that mortality rate was about six times higher
      during migration seasons than during stationary periods. However, total mortality
      was surprisingly similar between periods, which can be explained by the fact that
      risky migration periods are shorter than safer stationary periods. Nevertheless,
      more than half of the annual mortality occurred during migration. We also found
      spatiotemporal patterns in mortality: spring mortality occurred mainly in Africa
      in association with the crossing of the Sahara desert, while most mortality
      during autumn took place in Europe. Our results strongly suggest that events
      during the migration seasons have an important impact on the population dynamics
      of long-distance migrants. We speculate that mortality during spring migration
      may account for short-term annual variation in survival and population sizes,
      while mortality during autumn migration may be more important for long-term
      population regulation (through density-dependent effects).

PMID- 24102111
TI  - Biopharmaceutics permeability classification of lorcaserin, a selective 5
      hydroxytryptamine 2C agonist: method suitability and permeability class
      membership.
AB  - The objectives of the study were (1) to demonstrate that a Caco-2 cell-based
      permeability assay, developed in our laboratory, is suitable to identify the
      permeability classification according to the US Food and Drug Administration
      Biopharmaceutics Classification System guidance, and (2) to use the validated
      Caco-2 method to determine permeability class membership of lorcaserin.
      Lorcaserin, marketed in United States as Belviq, is a selective human 5
      hydroxytryptamine 2C agonist used for weight management. First, the permeability
      of twenty commercially available drugs was determined in the apical-to
      basolateral direction at a final concentration of 10 MUM, with the pH of
      transporter buffer in the apical and basolateral compartments being 6.8 and 7.4,
      respectively. A rank-order relationship between in vitro permeability results and
      the extent of human intestinal absorption for the drugs tested was observed.
      Second, the apparent permeability coefficient values of lorcaserin at 2, 20, and
      200 MUM and apical pH values of 6.8 and 7.4 in the apical-to-basolateral
      direction were determined using the validated method and found to be comparable
      to those of the high-permeability internal standard metoprolol. Lorcaserin
      permeability across Caco-2 cell monolayers was not dependent on the variation of
      apical pH. Furthermore, lorcaserin was not a substrate for efflux transporters
      such as P-glycoprotein. In conclusion, using the validated Caco-2 permeability
      assay, it was shown that lorcaserin is a highly permeable compound. 

PMID- 24102112
TI  - Yeast killer toxins, molecular mechanisms of their action and their applications.
AB  - Killer toxins secreted by some yeast strains are the proteins that kill sensitive
      cells of the same or related yeast genera. In recent years, many new yeast
      species have been found to be able to produce killer toxins against the
      pathogenic yeasts, especially Candida albicans. Some of the killer toxins have
      been purified and characterized, and the genes encoding the killer toxins have
      been cloned and characterized. Many new targets including different components of
      cell wall, plasma membrane, tRNA, DNA and others in the sensitive cells for the
      killer toxin action have been identified so that the new molecular mechanisms of
      action have been elucidated. However, it is still unknown how some of the newly
      discovered killer toxins kill the sensitive cells. Studies on the killer
      phenomenon in yeasts have provided valuable insights into a number of fundamental
      aspects of eukaryotic cell biology and interactions of different eukaryotic
      cells. Elucidation of the molecular mechanisms of their action will be helpful to
      develop the strategies to fight more and more harmful yeasts. 

PMID- 24102113
TI  - Engineering protein self-assembling in protein-based nanomedicines for drug
      delivery and gene therapy.
AB  - Lack of targeting and improper biodistribution are major flaws in current drug
      based therapies that prevent reaching high local concentrations of the
      therapeutic agent. Such weaknesses impose the administration of high drug doses,
      resulting in undesired side effects, limited efficacy and enhanced production
      costs. Currently, missing nanosized containers, functionalized for specific cell
      targeting will be then highly convenient for the controlled delivery of both
      conventional and innovative drugs. In an attempt to fill this gap, health-focused
      nanotechnologies have put under screening a growing spectrum of materials as
      potential components of nanocages, whose properties can be tuned during
      fabrication. However, most of these materials pose severe biocompatibility
      concerns. We review in this study how proteins, the most versatile functional
      macromolecules, can be conveniently exploited and adapted by conventional genetic
      engineering as efficient building blocks of fully compatible nanoparticles for
      drug delivery and how selected biological activities can be recruited to mimic
      viral behavior during infection. Although engineering of protein self-assembling
      is still excluded from fully rational approaches, the exploitation of protein
      nano-assemblies occurring in nature and the direct manipulation of protein
      protein contacts in bioinspired constructs open intriguing possibilities for
      further development. These methodologies empower the construction of new and
      potent vehicles that offer promise as true artificial viruses for efficient and
      safe nanomedical applications. 

PMID- 24102114
TI  - Effects of a fire response trait on diversification in replicated radiations.
AB  - Fire has been proposed as a factor explaining the exceptional plant species
      richness found in Mediterranean regions. A fire response trait that allows plants
      to cope with frequent fire by either reseeding or resprouting could
      differentially affect rates of species diversification. However, little is known
      about the generality of the effects of differing fire response on species
      evolution. We study this question in the Restionaceae, a family that radiated in
      Southern Africa and Australia. These radiations occurred independently and
      represent evolutionary replicates. We apply Bayesian approaches to estimate trait
      specific diversification rates and patterns of climatic niche evolution. We also
      compare the climatic heterogeneity of South Africa and Australia. Reseeders
      diversify faster than resprouters in South Africa, but not in Australia. We show
      that climatic preferences evolve more rapidly in reseeder lineages than in
      resprouters and that the optima of these climatic preferences differ between the
      two strategies. We find that South Africa is more climatically heterogeneous than
      Australia, independent of the spatial scale we consider. We propose that rapid
      shifts between states of the fire response trait promote speciation by separating
      species ecologically, but this only happens when the landscape is sufficiently
      heterogeneous. 

PMID- 24102115
TI  - Developing a reference material for diffusion-controlled formaldehyde emissions
      testing.
AB  - Formaldehyde, a known human carcinogen and mucous membrane irritant, is emitted
      from a variety of building materials and indoor furnishings. The drive to improve
      building energy efficiency by decreasing ventilation rates increases the need to
      better understand emissions from indoor products and to identify and develop
      lower emitting materials. To help meet this need, formaldehyde emissions from
      indoor materials are typically measured using environmental chambers. However,
      chamber testing results are frequently inconsistent and provide little insight
      into the mechanisms governing emissions. This research addresses these problems
      by (1) developing a reference formaldehyde emissions source that can be used to
      validate chamber testing methods for characterization of dynamic sources of
      formaldehyde emissions and (2) demonstrating that emissions from finite
      formaldehyde sources can be predicted using a fundamental mass-transfer model.
      Formaldehyde mass-transfer mechanisms are elucidated, providing practical
      approaches for developing diffusion-controlled reference materials that mimic
      actual sources. The fundamental understanding of emissions mechanisms can be used
      to improve emissions testing and guide future risk reduction actions. 

PMID- 24102116
TI  - Unique molecular dynamics of structural elements in an asymmetric Janus bisamide
      supramolecule characterized by solid-state NMR.
AB  - An asymmetric tapered Janus bisamide supramolecule consisting of 1,4-bis[3,4,5
      tris(alkan-1-yloxy)benzamido]benzene bisamide (abbreviated as C22PhBAEO3) can
      possess three-dimensional (3D) long-range order under mild thermal treatment
      conditions. To understand its structural formation and unique phase-transition
      processes, the locally detailed structure and molecular dynamics of its
      structural elements in disordered and ordered phases of C22PhBAEO3 were
      investigated using various solid-state (SS) NMR techniques at the atomic level.
      On the basis of the determined conformations and packing structures of the alkyl
      chains in ordered and disordered crystalline phases, along with the geometry and
      kinetic parameters of the structural elements' dynamics, this study addresses the
      self-assembly, the phase-transition mechanisms, and the relationship between the
      structure and dynamics of these asymmetric Janus bisamide supramolecules. 

PMID- 24102117
TI  - Rhodium(III)-catalyzed indole synthesis using N-N bond as an internal oxidant.
AB  - We report herein a Rh(III)-catalyzed cyclization of N-nitrosoanilines with
      alkynes for streamlined synthesis of indoles. The synthetic protocol features a
      distinct internal oxidant, N-N bond, as a reactive handle for catalyst turnover,
      as well as a hitherto tantalizingly elusive intermolecular redox-neutral
      manifold, predicated upon C-H activation, for the formation of a five-membered
      azaheterocycle. The compatibility of seemingly dichotomous acidic and basic
      conditions ensures reaction versatility for multifarious synthetic contexts. The
      tolerance of an array of auxiliary functional groups potentially permits
      predefined, programmable substitution patterns to be incorporated into the indole
      scaffold. Comprehensive mechanistic studies, under acidic condition, support
      [RhCp*](2+) as generally the catalyst resting state (switchable to
      [RhCp*(OOC(t)Bu)](+) under certain circumstance) and C-H activation as the
      turnover-limiting step. Given the variety of covalent linkages available for the
      nitroso group, this labile functionality is likely to be harnessed as a generic
      handle for strikingly diverse coupling reactions. 

PMID- 24102118
TI  - The clinical characteristics of retinal vasculitis in HLA-B27-positive patients.
AB  - PURPOSE: To investigate the ocular and systemic manifestations of retinal
      vasculitis in HLA-B27-positive patients. METHODS: Retrospective noncomparative
      case series of 9 HLA-B27-positive patients with uveitis and retinal vasculitis.
      Main outcome measures consisted of ocular and angiographic findings and
      assessment of any additional systemic disorders. RESULTS: Three male and 6 female
      HLA-B27-positive patients with a median age of 32 years were diagnosed with
      retinal vasculitis. Concurrent intraocular inflammation was noted in all
      patients. All patients suffered from extensive vasculitis of the large retinal
      veins. Five patients developed retinal vasculitis at the onset of uveitis and the
      remaining 4 exhibited retinal vasculitis 1-15 years after the onset of uveitis.
      Vascular occlusions occurred in 4 patients and subsequent neovascularizations
      developed in 3. Three patients were diagnosed with an HLA-B27-associated systemic
      disease. CONCLUSION: Retinal vasculitis may develop in the wake of HLA-B27
      associated uveitis and might represent a rare manifestation of HLA-B27-associated
      disease.

PMID- 24102121
TI  - Coupled exposure to ingredients of cosmetic products: I. Fragrances.
AB  - BACKGROUND: The use of cosmetics exposes consumers to mixtures of ingredients,
      many of which are contact allergens. Fragrances in particular are mostly used in
      combination; combinations of fragrances have been shown to enhance sensitization
      and elicitation. OBJECTIVE: To examine the pattern of co-exposure to fragrances
      in different categories of cosmetics, addressing the 26 fragrances that need to
      be identified on the label according to the Cosmetics Directive 76/768/EEC
      amended by 2003/15/EC. METHODS: A survey of products marketed in Germany,
      conducted in 2006-2009 by the Chemical and Veterinary Investigation Office in
      Karlsruhe, identified 4991 products with information on the presence of
      fragrances. The products were categorized according to Annex I to the Cosmetics
      Directive. The occurrence and co-occurrence of fragrances were analysed in
      tabular form and as social network diagrams. RESULTS: The median number of
      fragrances in products varied greatly between categories, ranging up to nine in
      perfumes. Limonene and linalool were the most commonly identified fragrances,
      often used together, but also with other fragrances. Thirty per cent of all
      products were not declared to contain any fragrances. CONCLUSIONS: For the first
      time, the pattern of co-exposure to fragrance ingredients in important categories
      of cosmetic products has been described. The observations illustrate and quantify
      the 'cocktail' of fragrance allergens that may facilitate sensitization.

PMID- 24102120
TI  - Source of biomass cooking fuel determines pulmonary response to household air
      pollution.
AB  - Approximately 3 billion people-half the worldwide population-are exposed to
      extremely high concentrations of household air pollution due to the burning of
      biomass fuels on inefficient cookstoves, accounting for 4 million annual deaths
      globally. Yet, our understanding of the pulmonary responses to household air
      pollution exposure and the underlying molecular and cellular events is limited.
      The two most prevalent biomass fuels in India are wood and cow dung, and typical
      24-hour mean particulate matter (PM) concentrations in homes that use these fuels
      are 300 to 5,000 MUg/m(3). We dissected the mechanisms of pulmonary responses in
      mice after acute or subchronic exposure to wood or cow dung PM collected from
      rural Indian homes during biomass cooking. Acute exposures resulted in robust
      proinflammatory cytokine production, neutrophilic inflammation, airway
      resistance, and hyperresponsiveness, all of which were significantly higher in
      mice exposed to PM from cow dung. On the contrary, subchronic exposures induced
      eosinophilic inflammation, PM-specific antibody responses, and alveolar
      destruction that was highest in wood PM-exposed mice. To understand the molecular
      pathways that trigger biomass PM-induced inflammation, we exposed Toll-like
      receptor (TLR)2-, TLR3-, TLR4-, TLR5-, and IL-1R-deficient mice to PM and found
      that IL-1R, TLR4, and TLR2 are the predominant receptors that elicit inflammatory
      responses via MyD88 in mice exposed to wood or cow dung PM. In conclusion, this
      study demonstrates that subchronic exposure to PM collected from households
      burning biomass fuel elicits a persistent pulmonary inflammation largely through
      activation of TLR and IL-1R pathways, which could increase the risk for chronic
      respiratory diseases. 

PMID- 24102122
TI  - Study of antidepressant-like activity of an enriched phloroglucinol fraction
      obtained from Hypericum caprifoliatum.
AB  - CONTEXT: Hypericum caprifoliatum Cham & Schlecht (Guttiferae) extracts have a
      potential antidepressant-like effect in rodents. However, the molecular
      mechanisms by which these extracts exert this effect remain unclear. OBJECTIVE:
      This study evaluated the effect of HC1, a fraction obtained from H. caprifoliatum
      enriched in phloroglucinol derivatives, on the Na+, K+ ATPase activity in mouse
      brain and verified the influence of veratrine on the effect of HC1 in the forced
      swimming test (FST). MATERIALS AND METHODS: Veratrine (0.06 mg/kg) and HC1 (360
      mg/kg) were given alone or combined i.p. 60 and p.o. 30 min, respectively, before
      FST. The effect of single and repeated administration (once a day for 3
      consecutive days) of HC1 (360 mg/kg) on Na+, K+ ATPase activity was evaluated ex
      vivo in the cerebral cortex and hippocampus of mice subjected or not to FST.
      RESULTS: HC1 reduced the immobility time (103.15 +/- 18.67 s), when compared to
      the control group (183.6 +/- 9.51 s). This effect was prevented by veratrine
      (151.75 +/- 22.19 s). Mice repeatedly treated with HC1 presented a significant
      increase in Na+, K+ ATPase activity, both in cerebral cortex (46 +/- 2.41 nmol
      Pi/min.mg protein) and hippocampus (49.83 +/- 2.31 nmol Pi/min.mg protein), in
      relation to the respective controls (30 +/- 2.66 and 29.83 +/- 2.31 nmol
      Pi/min.mg protein respectively). DISCUSSION AND CONCLUSION: The HC1
      antidepressant-like effect on FST might be related to its capacity to inhibit Na+
      influx. HC1 increases hippocampal and cortical Na+, K+ ATPase activities possibly
      through long-term regulatory mechanisms.

PMID- 24102123
TI  - Prevalence and impact of constipation and bowel dysfunction induced by strong
      opioids: a cross-sectional survey of 520 patients with cancer pain: DYONISOS
      study.
AB  - OBJECTIVE: To describe the prevalence of opioid-induced constipation (OIC) in
      patients with cancer pain according to the Knowles-Eccersley-Scott symptom score
      (KESS), the different symptoms of opioid-induced bowel dysfunction (OIBD), and to
      assess the impact of OIBD on patient's quality-of-life. METHODS: A cross
      sectional observational study, using the KESS questionnaire and the physician's
      subjective assessment of constipation, and other questionnaires and questions on
      constipation, OIBD, and quality-of-life, carried out on 1 day at oncology day
      centres and hospitals. RESULTS: Five hundred and twenty patients were enrolled at
      77 centres in France; 61.7% of patients (n = 321) showed a degree of constipation
      that is problematic for the patient according to KESS (between 9-39). Even more
      patients, 85.7% (n = 438), were considered constipated according to the
      physician's subjective assessment-despite laxative use (84.7% of patients).
      Quality-of-life was significantly reduced in constipated vs non-constipated
      patients for both PAC-QoL (p < 0.0001 for total score and each dimension) and the
      SF-12 questionnaires (statistically significant for all dimensions except
      physical state and role physical). OIC and OIBD led to hospitalization (16% of
      patients), pain (75% of patients), and frequent changes in opioid and laxative
      treatment. KEY LIMITATIONS: This cross-sectional study, in a selected population
      of cancer patients, has measured prevalence and impact of OIBD. Further
      confirmation could be sought through the use of longitudinal studies, and larger
      populations, such as non-cancer pain patients treated with opioids. CONCLUSIONS:
      Cancer patients taking opioids for pain are very frequently constipated, even if
      they are prescribed laxatives. This leads to relevant impairments of quality-of
      life.

PMID- 24102124
TI  - Learning with convex loss and indefinite kernels.
AB  - We consider a kind of kernel-based regression with general convex loss functions
      in a regularization scheme. The kernels used in the scheme are not necessarily
      symmetric and thus are not positive semidefinite; l(1)-norm of the coefficients
      in the kernel ensembles is taken as the regularizer. Our setting in this letter
      is quite different from the classical regularized regression algorithms such as
      regularized networks and support vector machines regression. Under an established
      error decomposition that consists of approximation error, hypothesis error, and
      sample error, we present a detailed mathematical analysis for this scheme and, in
      particular, its learning rate. A reweighted empirical process theory is applied
      to the analysis of produced learning algorithms, which plays a key role in
      deriving the explicit learning rate under some assumptions. 

PMID- 24102125
TI  - Information-maximization clustering based on squared-loss mutual information.
AB  - Information-maximization clustering learns a probabilistic classifier in an
      unsupervised manner so that mutual information between feature vectors and
      cluster assignments is maximized. A notable advantage of this approach is that it
      involves only continuous optimization of model parameters, which is substantially
      simpler than discrete optimization of cluster assignments. However, existing
      methods still involve nonconvex optimization problems, and therefore finding a
      good local optimal solution is not straightforward in practice. In this letter,
      we propose an alternative information-maximization clustering method based on a
      squared-loss variant of mutual information. This novel approach gives a
      clustering solution analytically in a computationally efficient way via kernel
      eigenvalue decomposition. Furthermore, we provide a practical model selection
      procedure that allows us to objectively optimize tuning parameters included in
      the kernel function. Through experiments, we demonstrate the usefulness of the
      proposed approach. 

PMID- 24102126
TI  - High-dimensional feature selection by feature-wise kernelized Lasso.
AB  - The goal of supervised feature selection is to find a subset of input features
      that are responsible for predicting output values. The least absolute shrinkage
      and selection operator (Lasso) allows computationally efficient feature selection
      based on linear dependency between input features and output values. In this
      letter, we consider a feature-wise kernelized Lasso for capturing nonlinear input
      output dependency. We first show that with particular choices of kernel
      functions, nonredundant features with strong statistical dependence on output
      values can be found in terms of kernel-based independence measures such as the
      Hilbert-Schmidt independence criterion. We then show that the globally optimal
      solution can be efficiently computed; this makes the approach scalable to high
      dimensional problems. The effectiveness of the proposed method is demonstrated
      through feature selection experiments for classification and regression with
      thousands of features. 

PMID- 24102127
TI  - Local linear approximation of the Jacobian matrix better captures phase resetting
      of neural limit cycle oscillators.
AB  - One effect of any external perturbations, such as presynaptic inputs, received by
      limit cycle oscillators when they are part of larger neural networks is a
      transient change in their firing rate, or phase resetting. A brief external
      perturbation moves the figurative point outside the limit cycle, a geometric
      perturbation that we mapped into a transient change in the firing rate, or a
      temporal phase resetting. In order to gain a better qualitative understanding of
      the link between the geometry of the limit cycle and the phase resetting curve
      (PRC), we used a moving reference frame with one axis tangent and the others
      normal to the limit cycle. We found that the stability coefficients associated
      with the unperturbed limit cycle provided good quantitative predictions of both
      the tangent and the normal geometric displacements induced by external
      perturbations. A geometric-to-temporal mapping allowed us to correctly predict
      the PRC while preserving the intuitive nature of this geometric approach. 

PMID- 24102129
TI  - Blocked 3*2 cross-validated t-test for comparing supervised classification
      learning algorithms.
AB  - In the research of machine learning algorithms for classification tasks, the
      comparison of the performances of algorithms is extremely important, and a
      statistical test of significance for generalization error is often used to
      perform it in the machine learning literature. In view of the randomness of
      partitions in cross-validation, a new blocked 3*2 cross-validation is proposed to
      estimate generalization error in this letter. We then conduct an analysis of
      variance of the blocked 3*2 cross-validated estimator. A relatively conservative
      variance estimator that considers the correlation between any two two-fold cross
      validations, and was previously neglected in 5*2 cross-validated t and F-tests is
      put forward. A corresponding test using this variance estimator is presented to
      compare the performances of algorithms. Simulated results show that the
      performance of our test is comparable with that of 5*2 cross-validated tests but
      with less computation complexity. 

PMID- 24102130
TI  - ParceLiNGAM: a causal ordering method robust against latent confounders.
AB  - We consider learning a causal ordering of variables in a linear nongaussian
      acyclic model called LiNGAM. Several methods have been shown to consistently
      estimate a causal ordering assuming that all the model assumptions are correct.
      But the estimation results could be distorted if some assumptions are violated.
      In this letter, we propose a new algorithm for learning causal orders that is
      robust against one typical violation of the model assumptions: latent
      confounders. The key idea is to detect latent confounders by testing independence
      between estimated external influences and find subsets (parcels) that include
      variables unaffected by latent confounders. We demonstrate the effectiveness of
      our method using artificial data and simulated brain imaging data. 

PMID- 24102128
TI  - Neural representation of spatial topology in the rodent hippocampus.
AB  - Pyramidal cells in the rodent hippocampus often exhibit clear spatial tuning in
      navigation. Although it has been long suggested that pyramidal cell activity may
      underlie a topological code rather than a topographic code, it remains unclear
      whether an abstract spatial topology can be encoded in the ensemble spiking
      activity of hippocampal place cells. Using a statistical approach developed
      previously, we investigate this question and related issues in greater detail. We
      recorded ensembles of hippocampal neurons as rodents freely foraged in one- and
      two-dimensional spatial environments and used a "decode-to-uncover" strategy to
      examine the temporally structured patterns embedded in the ensemble spiking
      activity in the absence of observed spatial correlates during periods of rodent
      navigation or awake immobility. Specifically, the spatial environment was
      represented by a finite discrete state space. Trajectories across spatial
      locations ("states") were associated with consistent hippocampal ensemble spiking
      patterns, which were characterized by a state transition matrix. From this state
      transition matrix, we inferred a topology graph that defined the connectivity in
      the state space. In both one- and two-dimensional environments, the extracted
      behavior patterns from the rodent hippocampal population codes were compared
      against randomly shuffled spike data. In contrast to a topographic code, our
      results support the efficiency of topological coding in the presence of sparse
      sample size and fuzzy space mapping. This computational approach allows us to
      quantify the variability of ensemble spiking activity, examine hippocampal
      population codes during off-line states, and quantify the topological complexity
      of the environment. 

PMID- 24102131
TI  - Single-snippet analysis for detection of postspike effects.
AB  - Corticomotoneuronal cells (CMN), located predominantly in the primary motor
      cortex, project directly to alpha motoneuronal pools in the spinal cord. The
      effects of CMN spikes on motoneuronal excitability are traditionally
      characterized by visualizing postspike effects (PSEs) in spike-triggered averages
      (SpTA; Fetz, Cheney, & German, 1976; Fetz & Cheney, 1980; McKiernan, Marcario,
      Karrer, & Cheney, 1998) of electromyography (EMG) data. Poliakov and Schieber
      (1998) suggested a formal test, the multiple-fragment analysis (MFA), to
      automatically detect PSEs. However, MFA's performance was not statistically
      validated, and it is unclear under what conditions it is valid. This paper's
      contributions are a power study that validates the MFA; an alternative test, the
      single-snippet analysis (SSA), which has the same functionality as MFA but is
      easier to calculate and has better power in small samples; a simple bootstrap
      simulation to estimate SpTA baselines with simulation bands that help visualize
      potential PSEs; and a bootstrap adjustment to the MFA and SSA to correct for
      nonlinear SpTA baselines.

PMID- 24102132
TI  - An epidemiological investigation of training and injury patterns in triathletes.
AB  - Associated with the trend towards increased health consciousness and fitness,
      triathlon has established itself as a sport for masses. The goals of this study
      were to evaluate injury risk factors of non-professional triathletes and to
      compare prospective and retrospective evaluation methods. Using an online survey,
      212 triathletes retrospectively answered a questionnaire about their training
      habits and injuries during the past 12 months. Forty-nine of these triathletes
      participated in a 12-month prospective trial. Injuries were classified with
      regard to the anatomical location, type of injury, incidence and associated risk
      factors. Most injuries occurred during running (50%) followed by cycling (43%)
      and swimming (7%). Fifty-four per cent (retrospective) and 22% (prospective) of
      the injuries were contusions and abrasions, 38% (retrospective) and 46%
      (prospective) were ligament and capsular injuries, 7% (retrospective) and 32%
      (prospective) were muscle and tendon injuries and 1% (retrospective) and 0%
      (prospective) were fractures. The incidence of an injury per 1000 training hours
      was 0.69 (retrospective) and 1.39 (prospective) during training and 9.24
      (retrospective) and 18.45 (prospective) during competition. The main risk factor
      for injury in non-professional triathlon is participation in a competitive
      triathlon event. A retrospective design may underestimate the rate of overuse
      injuries.

PMID- 24102135
TI  - Demographic and practice characteristics of Medicaid-participating dentists.
AB  - OBJECTIVES: The challenges entailed in dental Medicaid programs are well
      documented. To increase our understanding of Medicaid participation, we surveyed
      Florida dentists to determine the demographic and practice characteristics of
      Medicaid-participating dentists. METHODS: Our target population was practicing
      Florida dentists who treat children, including those who do not currently accept
      Medicaid as well as those who do. The final sample (n = 882) included (1)
      pediatric dentists and (2) general dentists who self-reported that they treat
      children. Participants completed a survey concerning their Medicaid
      participation. Analyses included survey-sample weighted chi-square tests and
      multivariable logistic regression. RESULTS: More than two-thirds of the sample
      dentists are not participating in Medicaid and will not consider doing so. Key
      findings are that Black dentists across the state and Hispanics in South Florida
      are more likely to participate in Medicaid than other groups of Florida dentists.
      Pediatric dentists are more likely to be Medicaid participants than general
      dentists, but nearly one-fifth of the pediatric dentists might quit
      participation. Non-Medicaid providers are more likely to report not being busy
      enough in their practice than Medicaid providers. CONCLUSIONS: If we are to
      address the shortage of Medicaid dental providers, increasing our understanding
      of how to capture the excess capacity among general dentists (the reported lack
      of busyness) in a way acceptable to dentists and to the State of Florida is an
      important first step. In addition, dental schools should consider implementing a
      track dedicated to training students for practice success within communities of
      highest dental need and to seek to increase the number of Black dental students.

PMID- 24102134
TI  - Discovery of an in vivo chemical probe of the lysine methyltransferases G9a and
      GLP.
AB  - Among epigenetic "writers", "readers", and "erasers", the lysine
      methyltransferases G9a and GLP, which catalyze mono- and dimethylation of histone
      H3 lysine 9 (H3K9me2) and nonhistone proteins, have been implicated in a variety
      of human diseases. A "toolkit" of well-characterized chemical probes will allow
      biological and disease hypotheses concerning these proteins to be tested in cell
      based and animal models with high confidence. We previously discovered potent and
      selective G9a/GLP inhibitors including the cellular chemical probe UNC0638, which
      displays an excellent separation of functional potency and cell toxicity.
      However, this inhibitor is not suitable for animal studies due to its poor
      pharmacokinetic (PK) properties. Here, we report the discovery of the first G9a
      and GLP in vivo chemical probe UNC0642, which not only maintains high in vitro
      and cellular potency, low cell toxicity, and excellent selectivity, but also
      displays improved in vivo PK properties, making it suitable for animal studies. 

PMID- 24102136
TI  - A novel subcutaneous infusion delivery system based on osmotic pump: in vitro and
      in vivo evaluation.
AB  - An economical, convenient portable drug delivery system combining osmotic pump
      with subcutaneous infusion was developed, which was composed of three primary
      components: water chamber, osmotic pump chamber and support base. Ceftriaxone
      sodium (CRO) was selected as the model drug and osmotic pump tablets were
      prepared. The influence of osmotic agents on drug release profiles was evaluated.
      As the adjustment made by the osmotic agents was limited, the compositions of
      semipermeable membrane were investigated to determine significant associations of
      factors based on orthogonal design. The in vitro release profiles of the optimum
      formulation achieved to the predetermined value (15 +/- 3 min for the initial
      release time T(i) and 5.75 +/- 0.25 h for the extent release time T(e)). The
      pharmacokinetic profiles of this drug delivery system were evaluated in Beagle
      dogs. In vivo results demonstrated that the osmotic pump subcutaneous infusion
      administration was equivalent to intravenous injection administration in terms of
      bioavailability. Moreover, constant drug plasma levels with minimized
      fluctuations could be achieved with this osmotic pump subcutaneous infusion
      system, compared with intravenous injection.

PMID- 24102137
TI  - Climate change heats matrix population models.
AB  - Metabolic theory predicts that demographic rates can be expressed as a function
      of environmental temperature. Amarasekare & Coutinho (2013) build a novel matrix
      model where demographic rates (fertility, mortality, development) vary according
      to expected rates of climate warming. They challenge recent studies that claim
      low population viability of tropical species based on rmax estimated from the
      Euler-Lotka equation, because the latter assumes a constant stage distribution
      that is unrealistic under fast rates of warming and for organisms with long
      development. In those cases, the measurement of the temperature responses of life
      history traits could be based in niche theory.

PMID- 24102138
TI  - Evolution and development of the homocercal caudal fin in teleosts.
AB  - The vertebrate caudal skeleton is one of the most innovative structures in
      vertebrate evolution and has been regarded as an excellent model for functional
      morphology, a discipline that relates a structure to its function. Teleosts have
      an internally-asymmetrical caudal fin, called the homocercal caudal fin, formed
      by the upward bending of the caudal-most portion of the body axis, the ural
      region. This homocercal type of the caudal fin ensures powerful and complex
      locomotion and is thought to be one of the most important evolutionary
      innovations for teleosts during adaptive radiation in an aquatic environment. In
      this review, we summarize the past and present research of fish caudal skeletons,
      especially focusing on the homocercal caudal fin seen in teleosts. A series of
      studies with a medaka spontaneous mutant have provided important insight into the
      evolution and development of the homocercal caudal skeleton. By comparing
      developmental processes in various vertebrates, we propose a scenario for
      acquisition and morphogenesis of the homocercal caudal skeleton during vertebrate
      evolution. 

PMID- 24102139
TI  - False-positive anti-retinal antibodies as a cause of psychogenic vision loss.
AB  - PURPOSE: To report a case of psychogenic vision loss caused by false-positive
      anti-retinal antibody testing. METHODS: We describe a case of visual and systemic
      symptoms following anti-retinal antibody detection. The case was analyzed for
      clinical presentation, diagnosis, and consequences of false-positive testing.
      RESULTS: The patient presented with decreased vision without detectable pathology
      on ophthalmic examination. Tests were ordered in search of a diagnosis, including
      an antibody test. Following detection of anti-retinal antibodies, the patient
      developed worsening visual symptoms and systemic manifestations. A repeat
      antibody test performed at our institution revealed negative results, which, in
      conjunction with lack of visual field expansion, confirmed our suspicion of
      psychogenic vision loss. CONCLUSIONS: Laboratory screening may be limited by test
      specificity and can lead to false-positive results, affecting the patient
      psychologically and clinically. Care must be taken in patients with positive anti
      retinal antibodies to ensure the presence of definitive disease before initiation
      of treatment.

PMID- 24102140
TI  - Evolution of paedomorphosis in plethodontid salamanders: ecological correlates
      and re-evolution of metamorphosis.
AB  - Life-history modes can profoundly impact the biology of a species, and a classic
      example is the dichotomy between metamorphic (biphasic) and paedomorphic
      (permanently aquatic) life-history strategies in salamanders. However, despite
      centuries of research on this system, several basic questions about the evolution
      of paedomorphosis in salamanders have not been addressed. Here, we use a nearly
      comprehensive, time-calibrated phylogeny of spelerpine plethodontids to
      reconstruct the evolution of paedomorphosis and to test if paedomorphosis is (1)
      reversible; (2) associated with living in caves; (3) associated with relatively
      dry climatic conditions on the surface; and (4) correlated with limited range
      size and geographic dispersal. We find that paedomorphosis arose multiple times
      in spelerpines. We also find evidence for re-evolution of metamorphosis after
      several million years of paedomorphosis in a lineage of Eurycea from the Edwards
      Plateau region of Texas. We also show for the first time using phylogenetic
      comparative methods that paedomorphosis is highly correlated with cave-dwelling,
      arid surface environments, and small geographic range sizes, providing insights
      into both the causes and consequences of this major life history transition. 

PMID- 24102141
TI  - Patch testing with serial dilutions and thin-layer chromatograms of oak moss
      absolutes containing high and low levels of atranol and chloroatranol.
AB  - BACKGROUND: Oak moss absolute (Evernia prunastri extract) contains a large number
      of substances, among them the potent allergens atranol and chloroatranol. Since
      2008, their content in oak moss absolute has been restricted by the International
      Fragrance Association to a maximum level of 100 ppm each. OBJECTIVES: To compare
      the elicitation capacities of a traditional (sample A) and a treated (sample B)
      oak moss absolute containing, in total, 27 000 and 66 ppm of atranol and
      chloroatranol, respectively, and to investigate reactions to components of oak
      moss absolute separated by thin-layer chromatography (TLC). METHODS: Fifteen oak
      moss-allergic subjects were patch tested with serial dilutions and TLC strips of
      samples A and B. RESULTS: Fifteen subjects reacted to sample A at concentrations
      <= 2.0%, and 2 subjects reacted to sample B at 2.0% but not to lower
      concentrations. Among 13 subjects reacting to the TLC strip of sample A, 11
      reacted to spots with retardation factor values corresponding to those of atranol
      and/or chloroatranol, and 11 reacted to other areas on the TLC strip. Only one
      subject reacted to the TLC strip of sample B. CONCLUSIONS: The patch test
      reactivity of sample B was significantly lower than that of sample A. The TLC
      patch tests indicate the presence of sensitizers other than atranol and
      chloroatranol in oak moss absolute.

PMID- 24102142
TI  - Thermoelectric efficiency of organometallic complex wires via quantum resonance
      effect and long-range electric transport property.
AB  - Superior long-range electric transport has been observed in several
      organometallic wires. Here, we discuss the role of the metal center in the
      electric transport and examine the possibility of high thermoelectric figure of
      merit (ZT) by controlling the quantum resonance effects. We examined a few metal
      center (and metal-free) terpyridine-based complexes by first-principles
      calculations and clarified the role of the metals in determining the transport
      properties. Quasi-resonant tunneling is mediated by organic compounds, and narrow
      overlapping resonance states are formed when d-electron metal centers are
      incorporated. Distinct length (L) and temperature (T) dependencies of thermopower
      from semiconductor materials or organic molecular junctions are presented in
      terms of atomistic calculations of ZT with and without considering the phonon
      thermal conductance. We present an alternative approach to obtain high ZT for
      molecular junctions by quantum effect. 

PMID- 24102144
TI  - Nonlinear THz conductivity dynamics in P-type CVD-grown graphene.
AB  - We report strong THz-induced transparency in CVD-grown graphene where 92-96% of
      the peak-field is transmitted compared to 74% at lower field strength. Time
      resolved THz pump/THz probe studies reveal that the absorption recovers in 2-3
      ps. The induced transparency is believed to arise from nonlinear pumping of
      carriers in graphene which suppresses the mobility and consequently the
      conductivity in a spectral region where the light-matter interaction is
      particularly strong. 

PMID- 24102145
TI  - Kinetics of biofilm formation and desiccation survival of Listeria monocytogenes
      in single and dual species biofilms with Pseudomonas fluorescens, Serratia
      proteamaculans or Shewanella baltica on food-grade stainless steel surfaces.
AB  - This study investigated the dynamics of static biofilm formation (100% RH, 15 
      degrees C, 48-72 h) and desiccation survival (43% RH, 15  degrees C, 21 days) of
      Listeria monocytogenes, in dual species biofilms with the common spoilage
      bacteria, Pseudomonas fluorescens, Serratia proteamaculans and Shewanella
      baltica, on the surface of food grade stainless steel. The Gram-negative bacteria
      reduced the maximum biofilm population of L. monocytogenes in dual species
      biofilms and increased its inactivation during desiccation. However, due to the
      higher desiccation resistance of Listeria relative to P. fluorescens and S.
      baltica, the pathogen survived in greater final numbers. In contrast, S.
      proteamaculans outcompeted the pathogen during the biofilm formation and
      exhibited similar desiccation survival, causing the N21 days of Serratia to be ca
      3 Log10(CFU cm(-2)) greater than that of Listeria in the dual species biofilm.
      Microscopy revealed biofilm morphologies with variable amounts of exopolymeric
      substance and the presence of separate microcolonies. Under these simulated food
      plant conditions, the fate of L. monocytogenes during formation of mixed biofilms
      and desiccation depended on the implicit characteristics of the co-cultured
      bacterium. 

PMID- 24102143
TI  - Characterization of molecular and cellular functions of the cyclin-dependent
      kinase CDK9 using a novel specific inhibitor.
AB  - BACKGROUND AND PURPOSE: The cyclin-dependent kinase CDK9 is an important
      therapeutic target but currently available inhibitors exhibit low specificity
      and/or narrow therapeutic windows. Here we have used a new highly specific CDK9
      inhibitor, LDC000067 to interrogate gene control mechanisms mediated by CDK9.
      EXPERIMENTAL APPROACH: The selectivity of LDC000067 was established in functional
      kinase assays. Functions of CDK9 in gene expression were assessed with in vitro
      transcription experiments, single gene analyses and genome-wide expression
      profiling. Cultures of mouse embryonic stem cells, HeLa cells, several cancer
      cell lines, along with cells from patients with acute myelogenous leukaemia were
      also used to investigate cellular responses to LDC000067. KEY RESULTS: The
      selectivity of LDC000067 for CDK9 over other CDKs exceeded that of the known
      inhibitors flavopiridol and DRB. LDC000067 inhibited in vitro transcription in an
      ATP-competitive and dose-dependent manner. Gene expression profiling of cells
      treated with LDC000067 demonstrated a selective reduction of short-lived mRNAs,
      including important regulators of proliferation and apoptosis. Analysis of de
      novo RNA synthesis suggested a wide ranging positive role of CDK9. At the
      molecular and cellular level, LDC000067 reproduced effects characteristic of CDK9
      inhibition such as enhanced pausing of RNA polymerase II on genes and, most
      importantly, induction of apoptosis in cancer cells. CONCLUSIONS AND
      IMPLICATIONS: Our study provides a framework for the mechanistic understanding of
      cellular responses to CDK9 inhibition. LDC000067 represents a promising lead for
      the development of clinically useful, highly specific CDK9 inhibitors.

PMID- 24102146
TI  - Inhibition of hyaluronan synthesis in rats reduces renal ability to excrete fluid
      and electrolytes during acute hydration.
AB  - BACKGROUND: Hyaluronan (HA) is the dominant glycosaminoglycan in the
      renomedullary interstitium. Renomedullary HA has been implicated in tubular fluid
      handling due to its water-attracting properties and the changes occurring in
      parallel to acute variations in the body hydration status. METHODS: HA production
      was inhibited by 4-methylumbelliferone (4-MU in drinking water for 5 days, 1.45
      +/- 0.07 g/day/kg body weight) in rats prior to hydration. RESULTS: Following
      hypotonic hydration for 135 min in control animals, diuresis and osmotic
      excretion increased while sodium excretion and glomerular filtration rate (GFR)
      remained unchanged. The medullary and cortical HA contents were 7.85 +/- 1.29
      ng/mg protein and 0.08 +/- 0.01 ng/mg protein, respectively. Medullary HA content
      after 4-MU was 38% of that in controls (2.98 +/- 0.95 ng/g protein, p < 0.05),
      while the low cortical levels were unaffected. Baseline urine flow was not
      different from that in controls. The diuretic response to hydration was, however,
      only 51% of that in controls (157 +/- 36 versus 306 +/- 54 ul/g kidney weight/135
      min, p < 0.05) and the osmolar excretion only 47% of that in controls (174 +/- 47
      versus 374 +/- 41 uOsm/g kidney weight/135 min, p < 0.05). Sodium excretion, GFR,
      and arterial blood pressure were similar to that in control rats and unaltered
      during hydration. CONCLUSIONS: Reduction of renomedullary interstitial HA using 4
      MU reduces the ability of the kidney to respond appropriately upon acute
      hydration. The results strengthen the concept of renomedullary HA as a modulator
      of tubular fluid handling by changing the physicochemical properties of the
      interstitial space.

PMID- 24102147
TI  - U22 protocol as measure of symptomatic improvement after catheter ablation of
      atrial fibrillation.
AB  - INTRODUCTION: Left atrial catheter ablation is useful as symptomatic treatment in
      selected patients with atrial fibrillation (AF). Evaluation requires measurement
      of arrhythmia-related symptoms. Many of the published protocols have drawbacks
      and have been used in AF only, with no possible comparison to other ablations
      that compete for the same resources. U22 is a published protocol that quantifies
      paroxysmal tachycardia symptoms through scales with 11 answer alternatives,
      translated into discrete numerical scales 0-10. It has been shown to reflect the
      clinical improvement after ablation of supraventricular tachycardia. Here we
      report the use of U22 in measuring improvement after catheter ablation for AF.
      MATERIAL AND METHODS: A total of 105 patients underwent first-time ablation for
      AF and answered U22 and SF-36 forms at baseline and follow-up 304 (SD 121) days
      after ablation. Independently, the patients underwent a clinical follow-up. All
      decisions regarding medication and reablation were taken without knowledge of the
      symptom scores. Results. The U22 scores for well-being, arrhythmia as cause for
      impaired well-being, derived time-aspect score for arrhythmia, and discomfort
      during attack detected relevant improvements of symptoms after the ablation. U22
      showed larger improvement in patients undergoing only one procedure than in
      patients who later underwent repeated interventions, thus reflecting the
      independent clinical decision for reablation. CONCLUSION: U22 quantifies the
      symptomatic improvement after AF ablation with adequate internal consistency and
      construct validity. U22 mirrors aspects of the arrhythmia symptomatology other
      than SF-36.

PMID- 24102148
TI  - Twelve-month follow-up of advance provision of emergency contraception among
      teenage girls in Sweden-a randomized controlled trial.
AB  - OBJECTIVE: The objective of this study was to evaluate the effect of an
      intervention with advance provision of emergency contraceptive pills (ECP),
      condoms, and extended information to a targeted group of teenage girls, compared
      with a control group, 12 months after intervention. MATERIAL AND METHODS: A
      randomized controlled trial among 420 girls, 15-19 years old, requesting
      emergency contraception at a youth clinic in Sweden was carried out. Data were
      collected by a questionnaire at the initial visit and structured telephone
      interviews 12 months after enrolment. Differences between the intervention group
      and the control group regarding ECP use, time interval from unprotected
      intercourse to ECP intake, contraceptive use, and sexual risk-taking were
      analysed. RESULTS: One year after the intervention 62% of the girls could be
      reached for follow-up. The girls in the intervention group reported a shorter
      time interval (mean 15.3 hours) from unprotected intercourse to ECP intake
      compared to the control group (mean 25.8 hours) (p = 0.019), without any evidence
      of decreased use of contraceptives or increased sexual risk-taking. CONCLUSION:
      Even up to 12 months following the intervention, advance provision of ECP at one
      single occasion, to a specific target group of adolescent girls, shortens the
      time interval from unprotected intercourse to pill intake, without jeopardizing
      contraceptive use or increasing sexual risk-taking. Considering the clinical
      relevance of these results, we suggest that advance provision of ECP could be
      implemented as a routine preventive measure for this target group.

PMID- 24102149
TI  - Alternative diagnosis to heparin-induced thrombocytopenia in two critically ill
      patients despite a positive PF4/heparin-antibody test.
AB  - Thrombocytopenia can cause diagnostic challenges in patients who have received
      heparin. Heparin-induced thrombocytopenia (HIT) is often considered in the
      differential diagnosis, and a positive screening can be mistaken as confirmation
      of the disorder. We present two patients who both received low-molecular-weight
      heparin for several days. In the first patient, clinical judgment rejected the
      suspicion of HIT despite a positive screening assay, and treatment for the
      alternative diagnosis of post-transfusion purpura was correctly initiated. In the
      second patient, the inaccurate diagnosis HIT was pursued due to a positive
      screening assay, while the alternative diagnosis of drug-dependent
      thrombocytopenia caused by piperacillin/tazobactam was rejected. This resulted in
      re-exposure to piperacillin/tazobactam which caused a second episode of severe
      thrombocytopenia. A positive screening assay for platelet factor 4/heparin
      antibody should be verified by a functional assay, especially in patients with
      low pretest probability for HIT.

PMID- 24102150
TI  - Correlates of depressive illness among the elderly in a mixed urban community in
      Lagos, Nigeria.
AB  - OBJECTIVES: Little is known about the factors associated with depression among
      elderly Nigerians despite research evidence suggesting that some correlates of
      depression may be important in early detection, treatment and prognosis. This
      study aimed to determine the correlates of depression among a community based
      elderly population. METHODS: The study population made up of 350 consenting
      participants was selected using multistage stratified random sampling technique.
      Face-to-face interviews were conducted among the participants using a research
      instrument consisting of two parts: a self-designed questionnaire to elicit their
      socio-demographic profile, level of social support as well as their health status
      and the 30-item Geriatric Depression Scale to diagnose depression using cut-off
      score >=11. Both the English and Yoruba versions of the study instruments were
      used depending on the level of education of the participants. RESULTS: Depression
      was found to be associated with being younger old (chi(2) = 6.19, p = 0.045),
      prolonged stay in current residence (chi(2) = 6.62, p = 0.01), living in less
      developed area of the community and not having children (chi(2) = 0.03, p =
      0.01), while higher social support (chi(2) = 4.19, p = 0.041) seems protective.
      However, only low social support (odds ratio [OR] = 0.573; 95% confidence
      interval [CI], 0.330-0.994; p = 0.048), living in less developed area (OR =
      5.342; 95% CI = 1.027, 27.776; p = 0.046) and prolonged stay in current residence
      (OR = 0.407; 95% CI = 0.205, 0.806; p = 0.01) independently predicted depression
      in participants. CONCLUSION: To enhance early detection and treatment of
      depressive disorders in the elderly, physicians should be alert to the diagnosis
      of depression in late life, especially among the younger old, elderly not having
      children, those with low social support as well as prolonged stay in a residence
      and living in less developed parts of the community. Further research is needed
      to shed light on the intriguing link between depression and associated factors in
      geriatric population.

PMID- 24102151
TI  - A steady increase in nontuberculous mycobacteriosis mortality and estimated
      prevalence in Japan.
AB  - RATIONALE: Pulmonary disease caused by nontuberculous mycobacteria is generally
      reported to have a good prognosis. However, the actual mortality rate over time
      has not been reported in a large-scale survey. OBJECTIVES: To determine the
      annual trend in mortality from nontuberculous mycobacteriosis, based on nearly
      four decades of patient data, and to estimate the prevalence of these cases in
      2005. METHODS: The annual mortality rate and regional distribution of
      nontuberculous mycobacteriosis-related deaths in Japan were obtained from Vital
      Statistics of Japan, which is published annually. The crude and age-adjusted
      mortality rates and associated regional differences were calculated from the
      Japanese census data. A 5-year follow-up study including 309 patients with
      pulmonary nontuberculous mycobacteriosis who visited and registered at our
      institute from 2004 to 2006 was conducted to determine the 5-year prognosis and
      the annual mortality rate. MEASUREMENTS AND MAIN RESULTS: The crude mortality
      rates for both sexes have increased since 1970, and the mortality rate from
      pulmonary disease was greater in women after 2005. The age-adjusted rates of
      disease also showed a gradual increase until 2010 in women. Geographically,
      higher standardized mortality ratios were observed in middle and western Japan,
      particularly in the southern coastal regions along the Pacific Ocean. In a
      clinical follow-up study, the mortality rate was approximately 1-2% annually. The
      prevalence of pulmonary nontuberculous mycobacteriosis was estimated to be 6- to
      10-fold higher than the annual incidence. CONCLUSIONS: There was a constant and
      steady increase of nontuberculous mycobacteriosis-related mortality in Japan, and
      this mortality rate showed significant geographical variation. The prevalence of
      environmental mycobacterial disease in Japan is higher than reported in most
      other countries.

PMID- 24102152
TI  - Detection of extracellular RNAs in cancer and viral infection via tethered
      cationic lipoplex nanoparticles containing molecular beacons.
AB  - Noninvasive early detection methods have the potential to reduce mortality rates
      of both cancer and infectious diseases. Here, we present a novel assay by which
      tethered cationic lipoplex nanoparticles containing molecular beacons (MBs) can
      capture cancer cell-derived exosomes or viruses and identify encapsulated RNAs in
      a single step. A series of ultracentrifugation and Exoquick isolation kit were
      first used to isolate exosomes from the cell culture medium and human serum,
      respectively. Cationic lipoplex nanoparticles linked onto the surface of a thin
      glass plate capture negatively charged viruses or cell-secreted exosomes by
      electrostatic interactions to form larger nanoscale complexes. Lipoplex/virus or
      lipoplex/exosome fusion leads to the mixing of viral/exosomal RNAs and MBs within
      the lipoplexes. After the target RNAs specially bind to the MBs, exosomes
      enriched in target RNAs are readily identified by the fluorescence signals of
      MBs. The in situ detection of target extracellular RNAs without diluting the
      samples leads to high detection sensitivity not achievable by existing methods,
      e.g., quantitative reverse transcription-polymerase chain reaction (qRT-PCR).
      Here we demonstrate this concept using lentivirus and serum from lung cancer
      patients. 

PMID- 24102153
TI  - Combination drug therapy for patients with intractable ventricular tachycardia
      associated with right ventricular cardiomyopathy.
AB  - BACKGROUND: Drug therapy for patients with right ventricular (RV) cardiomyopathy
      refractory to single-drug therapy and ablation has not been well defined.
      METHODS: We reviewed our entire RV cardiomyopathy database (31 patients) and
      found four patients presenting with ventricular arrhythmias of RV origin
      refractory to single-drug therapy. These patients underwent complete evaluation
      for arrhythmogenic right ventricular cardiomyopathy (ARVC). RESULTS: Following
      the revised 2010 task force criteria, of these four patients, three were
      diagnosed with ARVC, and one with cardiac sarcoidosis. These patients proved to
      be refractory to drug monotherapy and either failed or deemed to not be
      candidates for endocardial ablation. Their arrhythmias were ultimately controlled
      with combinations of sotalol, flecainide, and mexiletine. CONCLUSIONS: In our
      experience, combination drug therapy is an effective treatment strategy for
      patients with ventricular tachycardia refractory to monotherapy and, in some
      cases, ablation. In addition, flecainide appears to be safe and effective for
      those with RV cardiomyopathy without significant left ventricular dysfunction.

PMID- 24102154
TI  - Asymmetric organic-inorganic hybrid membrane formation via block copolymer
      nanoparticle co-assembly.
AB  - A facile method for forming asymmetric organic-inorganic hybrid membranes for
      selective separation applications is developed. This approach combines co
      assembly of block copolymer (BCP) and inorganic nanoparticles (NPs) with non
      solvent induced phase separation. The method is successfully applied to two
      distinct molar mass BCPs with different fractions of titanium dioxide (TiO2) NPs.
      The resulting hybrid membranes exhibit structural asymmetry with a thin
      nanoporous surface layer on top of a macroporous fingerlike support layer. Key
      parameters that dictate membrane surface morphology include the fraction of
      inorganics used and the length of time allowed for surface layer development. The
      resulting membranes exhibit both good selectivity and high permeability (3200 +/-
      500 Lm(-2) h(-1) bar(-1)). This fast and straightforward synthesis method for
      asymmetric hybrid membranes provides a new self-assembly platform upon which
      multifunctional and high-performance organic-inorganic hybrid membranes can be
      formed. 

PMID- 24102156
TI  - Phaeochromocytoma [corrected] crisis.
AB  - Phaeochromocytoma [corrected] crisis is an endocrine emergency associated with
      significant mortality. There is little published guidance on the management of
      phaeochromocytoma [corrected] crisis. This clinical practice update summarizes
      the relevant published literature, including a detailed review of cases published
      in the past 5 years, and a proposed classification system. We review the
      recommended management of phaeochromocytoma [corrected] crisis including the use
      of alpha-blockade, which is strongly associated with survival of a crisis.
      Mechanical circulatory supportive therapy (including intra-aortic balloon pump or
      extra-corporeal membrane oxygenation) is strongly recommended for patients with
      sustained hypotension. Surgical intervention should be deferred until medical
      stabilization is achieved.

PMID- 24102155
TI  - Microscale speciation of arsenic and iron in ferric-based sorbents subjected to
      simulated landfill conditions.
AB  - During treatment for potable use, water utilities generate arsenic-bearing ferric
      wastes that are subsequently dispatched to landfills. The biogeochemical
      weathering of these residuals in mature landfills affects the potential
      mobilization of sorbed arsenic species via desorption from solids subjected to
      phase transformations driven by abundant organic matter and bacterial activity.
      Such processes are not simulated with the toxicity characteristic leaching
      procedure (TCLP) currently used to characterize hazard. To examine the effect of
      sulfate on As retention in landfill leachate, columns of As(V) loaded amorphous
      ferric hydroxide were reacted biotically at two leachate sulfate concentrations
      (0.064 mM and 2.1 mM). After 300 days, ferric sorbents were reductively
      dissolved. Arsenic released to porewaters was partially coprecipitated in mixed
      valent secondary iron phases whose speciation was dependent on sulfate
      concentration. As and Fe XAS showed that, in the low sulfate column, 75-81% of
      As(V) was reduced to As(III), and 53-68% of the Fe(III) sorbent was transformed,
      dominantly to siderite and green rust. In the high sulfate column, Fe(III) solids
      were reduced principally to FeS(am), whereas As(V) was reduced to a polymeric
      sulfide with local atomic structure of realgar. Multienergy micro-X-ray
      fluorescence (ME-MUXRF) imaging at Fe and As K-edges showed that As formed
      surface complexes with ferrihydrite > siderite > green rust in the low sulfate
      column; while discrete realgar-like phases formed in the high sulfate systems.
      Results indicate that landfill sulfur chemistry exerts strong control over the
      potential mobilization of As from ferric sorbent residuals by controlling
      secondary As and Fe sulfide coprecipitate formation. 

PMID- 24102157
TI  - The Levy flight foraging hypothesis in a pelagic seabird.
AB  - Levy flight foraging represents an innovative paradigm for the analysis of animal
      random search by including models of heavy-tailed distribution of move length,
      which complements the correlated random walk paradigm that is founded on Brownian
      walks. Theory shows that the efficiency of the different foraging tactics is a
      function of prey abundance and dynamics with Levy flight being especially
      efficient in poor prey fields. Levy flights have been controversial in some
      quarters, because they previously have been wrongly ascribed to many species
      through the employment of inappropriate statistical techniques and by
      misunderstanding movement pattern data. More recent studies using state-of-the
      art statistical tools have, however, provided seemingly compelling evidence for
      Levy flights. In this study, we employ these maximum-likelihood methods and their
      Bayesian equivalents by analysing both turning angles and move length
      distributions. We tested, for compliance with Levy flight foraging, a set of 77
      independent foraging trajectories of Cory's shearwaters Calonectris diomedea
      diomedea. Birds were tagged with high-resolution GPS loggers in two Mediterranean
      colonies (Linosa and Tremiti) during both incubation and chick rearing. We found
      that the behaviour of six birds was fitted by a correlated random walk; the
      movement of 32 birds was better represented by adaptive correlated random walks
      by switching from intensive to extensive searches; and the trajectories of 36
      birds were fitted by a Levy flight pattern of movement. The probability of
      performing Levy flights was higher for trips during chick provisioning when
      shearwaters were forced to forage in suboptimal areas. This study supports Levy
      flight foraging as an appropriate framework to analyse search tactics in this
      pelagic bird species and highlights that the adoption of a given search strategy
      is a function of biological and ecological constraints. 

PMID- 24102158
TI  - Environmental enrichment and social interaction improve cognitive function and
      decrease reactive oxidative species in normal adult mice.
AB  - Environmental stimulation and increased social interactions stimulate cognitive
      performance, while decrease in these parameters can exacerbate cognitive decline
      as a function of illness, injury, or age. We examined the impact of environmental
      stimulation and social interactions on cognitive performance in healthy adult
      C57B1/6J mice. Mice were housed for 1 month individually or in groups of three
      (to prevent or allow social interaction) in either a standard environment (SE) or
      an enlarged cage containing nesting material and items classically utilized to
      stimulate exploration and activity ("enriched environment"; EE). Cognitive
      performance was tested by Y maze navigation and Novel Object Recognition (NOR;
      which compares the relative amount of time mice spent investigating a novel vs. a
      familiar object). Mice maintained for 1 month under isolated conditions in the SE
      statistically declined in performance versus baseline in the Y maze (p < 0.02;
      ANOVA). Performance under all other conditions did not change from baseline.
      Maintenance in groups in the SE statistically improved NOR (p < 0.01), whereas
      maintenance in isolation in the SE did not alter performance from baseline.
      Maintenance in the EE statistically improved performance in NOR for mice housed
      in groups and individually (p < 0.01). Maintenance under isolated conditions
      slightly increased reactive oxygen/nitrogen species (ROS/RNS) in brain.
      Environmental enrichment did not influence ROS/RNS. These findings indicate that
      environmental and social enrichment can positively influence cognitive
      performance in healthy adult mice, and support the notion that proactive
      approaches may delay age-related cognitive decline. 

PMID- 24102159
TI  - The percutaneous permeability and absorption of dexamethasone esters in diabetic
      rats: a preliminary study.
AB  - To evaluate the influence of diabetes on the permeation of dexamethasone acetate
      (DA) and dexamethansone sodium phosphate (DSP), the two major dexamethansone
      esters in clinical practice, when applied percutaneously, histochemical staining
      was used to determine the skin morphology; improved Franz diffusion cells and
      microdialysis were used to assess the percutaneous permeation of DA and DSP in
      normal and diabetic rats. Histopathological examination showed that the epidermal
      tissue of diabetic rat was much thinner, the epidermal cell layer was less clear
      and the stratified arrangement of epidemic cell had almost disappeared and
      progressive atrophy were developed on the subcutaneous fat. In vitro studies
      showed that the cumulative and the penetrated DSP amount in Group DM were higher.
      The mean flux value and the mean depositional amount of Group DM were increased
      significantly compared to those of Group CTL, whereas the amount of DA
      penetrating was of no difference. Microdialysis indicated that there was no
      significant difference between Group CTL and Group DM for all the pharmacokinetic
      parameters of DA. In contrast, the subcutaneous AUCall values and the C(max) of
      DSP were significantly increased compared to the control. In conclusion, diabetic
      rat skin significantly increased the percutaneous permeation of DSP but had no
      effect on that of DA. It suggests that patients with diabetes should consider the
      dose of administration when using DA, DSP or other glucocorticoids topically, as
      different liposolubilities may play some role in the permeability of these
      compounds via diabetic skin.

PMID- 24102160
TI  - Decay kinetics of benzophenone triplets and corresponding free radicals in soft
      and rigid polymers studied by laser flash photolysis.
AB  - The kinetics of transients formed under photoexcitation of benzophenone (B)
      dissolved in three different polymers was studied by ns laser flash photolysis.
      These polymers were the soft rubbers poly (ethylene-co-butylene) (EB),
      polystyrene block-poly(ethylene-ran-butylene)-block-polystyrene (SEBS) and hard
      polystyrene (PS). We monitored the decay kinetics of triplet state (3)B(*) and of
      ketyl radicals BH(?). We observed exponential decay of (3)B(*) and two-stage
      decay kinetics of BH(?) in EB. The first stage is a fast cage recombination of a
      radical pair (BH(?), radical of polymer R(?)). The second slow stage of BH(?)
      decay follows the second-order law with a relatively high rate constant, which
      corresponds to recombination of BH(?) in a homogeneous liquid with a viscosity of
      only ~0.1 P (about five times of 2-propanol viscosity). Application of a magnetic
      field (MF) of 0.2 T leads to deceleration of both stages of BH(?) decay in EB by
      approximately 20%. Decay kinetics of both transients were observed in SEBS. There
      was no MF effect on BH(?) decay in SEBS. We only observed (3)B(*) in PS. Decay
      kinetics of (3)B(*) in this case were described as polychromatic dispersive first
      order kinetics. We discuss the effects of polymer structure on transient kinetics
      and the MF effect.

PMID- 24102161
TI  - Clicking 3'-azidothymidine into novel potent inhibitors of human immunodeficiency
      virus.
AB  - 3'-Azidothymidine (AZT) was the first approved antiviral for the treatment of
      human immunodeficiency virus (HIV). Reported efforts in clicking the 3'-azido
      group of AZT have not yielded 1,2,3-triazoles active against HIV or any other
      viruses. We report herein the first AZT-derived 1,2,3-triazoles with
      submicromolar potencies against HIV-1. The observed antiviral activities from the
      cytopathic effect (CPE) based assay were confirmed through a single replication
      cycle assay. Structure-activity-relationship (SAR) studies revealed two
      structural features key to antiviral activity: a bulky aromatic ring and the 1,5
      substitution pattern on the triazole. Biochemical analysis of the corresponding
      triphosphates showed lower ATP-mediated nucleotide excision efficiency compared
      to AZT, which along with molecular modeling suggests a mechanism of preferred
      translocation of triazoles into the P-site of HIV reverse transcriptase (RT).
      This mechanism is corroborated with the observed reduction of fold resistance of
      the triazole analogue to an AZT-resistant HIV variant (9-fold compared to 56-fold
      with AZT). 

PMID- 24102162
TI  - Postsynthetic functionalization of a hollow silica nanoreactor with manganese
      oxide-immobilized metal nanocrystals inside the cavity.
AB  - A postsynthetic protocol of functionalizing the preformed hollow nanoparticles
      with metal nanocrystals was developed based on galvanic replacement reaction on
      the Mn3O4 surface inside the cavity. The developed protocol produced hollow
      nanoreactor systems, in which a high density of ultrafine catalytic nanocrystals
      of a range of noble metals, such as Pd, Pt, Rh, and Ir and their alloys, are
      dispersively immobilized on an interior surface enclosed by a selectively
      permeable silica shell. The fabricated hollow nanoreactor exhibited highly
      enhanced activity, selectivity, and recyclability in catalyzing the oxidation of
      hydrosilanes, which are attributable to the synergistic combination of the porous
      silica nanoshell and the oxide-immobilized catalyst system. 

PMID- 24102163
TI  - Survey of central venous catheterisation practice in Sweden.
AB  - BACKGROUND: Clinical guidelines on central venous catheterisation were introduced
      by the Swedish Society of Anaesthesiology and Intensive Care Medicine in 2011.
      The purpose of this study was to investigate current national practice and assess
      to what extent these guidelines influence clinical routines in Swedish operating
      wards and intensive care units. METHODS: An invitation to participate in an
      online survey regarding central venous catheterisation was sent to 65 departments
      of anaesthesiology and intensive care medicine in Sweden. The survey aimed at
      investigating routine standards (part 1) and 24-h clinical practice (part 2).
      RESULTS: Forty-seven (72%) and 49 (75%) of 65 departments took part in parts 1
      and 2, respectively, and 73% adhered to the national guidelines. Many units
      monitored mechanical (42%) and infectious (69%) complications. Ultrasound was
      used by more than 50%. Checklists for insertion were used by 22%. Physicians
      inserted most catheters. No serious complications were reported during the 24-h
      study period. Ninety-seven non-tunnelled, 17 venous ports, 9 tunnelled and 8
      peripheral central venous catheters were inserted. Ninety-three (71%) catheters
      were inserted in operating rooms, and 31 (24%) in intensive care units.
      Catheterisations were followed up by chest X-ray in most departments. CONCLUSION:
      Knowledge of the Swedish guidelines was adequate, and most participating
      departments had local catheterisation routines. We could identify some variation
      in practice, but overall adherence to the guidelines was good. Nevertheless,
      monitoring of procedures and complications of cannulation and maintenance could
      be in need of improvement.

PMID- 24102164
TI  - A novel 785-nm laser diode-based system for standardization of cell culture
      irradiation.
AB  - OBJECTIVE: The purpose of this study was to develop a novel device that
      concatenates alignment of infrared lasers and parallel procedure of irradiation.
      The purpose of this is to seek standardization of in vitro cell irradiation,
      which allows analysis and credible comparisons between outcomes of different
      experiments. BACKGROUND DATA: Experimental data obtained from infrared laser
      therapies have been strongly dependent upon the irradiation setup. Although
      further optical alignment is difficult to achieve, in contact irradiation it
      usually occurs. Moreover, these methods eventually use laser in a serial
      procedure, extending the time to irradiate experimental samples. METHODS: A
      LASERTable (LT) device was designed to provide similar infrared laser irradiation
      in 12 wells of a 24 well test plate. It irradiated each well by expanding the
      laser beam until it covers the well bottom, as occurs with unexpanded
      irradiation. To evaluate the effectiveness of this device, the spatial
      distribution of radiation was measured, and the heating of plain culture medium
      was monitored during the LT operation. The irradiation of LT (up to 25 J/cm(2) -
      20 mW/cm(2); 1.250 sec) was assessed on odontoblast-like cells adhered to the
      bottom of wells containing 1 mL of plain culture medium. Cell morphology and
      metabolism were also evaluated. RESULTS: Irradiation with LT presented a Gaussian
      like profile when the culture medium was not heated >1 degrees C. It was also
      observed that the LT made it 10 times faster to perform the experiment than did
      serial laser irradiation. In addition, the data of this study revealed that the
      odontoblast-like cells exposed to low-level laser therapy (LLLT) using the LT
      presented higher metabolism and normal morphology. CONCLUSIONS: The experimental
      LASERTable assessed in this study provided parameters for standardization of
      infrared cell irradiation, minimizing the time spent to irradiate all samples.
      Therefore, this device is a helpful tool that can be effectively used to evaluate
      experimental LLLT protocols.

PMID- 24102165
TI  - The adjunct therapeutic effect of lasers with medication in the management of
      orofacial pain: double blind randomized controlled trial.
AB  - OBJECTIVE: This study aimed to evaluate the efficacy of laser therapy in
      conjunction with a pharmaceutical approach to alleviate myofascial pain
      dysfunction syndrome. BACKGROUND DATA: A few clinical studies have evaluated the
      analgesic effect of laser therapy on orofacial pain, most of which reported
      controversial results. Myofascial pain dysfunction syndrome (MPDS), trigeminal
      neuralgia, and atypical facial pain are the most common facial pain. METHODS: A
      double-blind randomized controlled trial was designed to evaluate the therapeutic
      effect of GaAs laser (peak power 10 W; pulse frequency 3000 Hz; average power
      0.012 W; wavelength 980 nm; irradiation duration 300 sec; and dose 12.73 J/cm(2))
      on the management of common orofacial pain. The laser group (n=30) received 10
      sessions of treatment with GaAs laser. The control group (n=30) was treated
      identically with sham laser. All patients received the appropriate pharmaceutical
      treatment as well. Visual analog scale (VAS) was recorded for all patients at
      baseline, and immediately, 2, and 4 months after the final treatment session. The
      qualitative variables among the groups were compared using the chi(2) test.
      RESULTS: Both groups demonstrated a significant reduction in pain with the
      progression of time (p<0.05). The difference between the two groups was not
      significant (p>0.05). Whereas laser therapy in the present study failed to show
      any significance over the control group, the role of covariates such as radiation
      parameters (wave length, dose) should not be overlooked. CONCLUSIONS: We found no
      significant level of efficacy for the GaAs laser in the management of common
      orofacial pain. Further studies are suggested to evaluate the efficacy of other
      types of lasers with different parameters in the management of orofacial pains.

PMID- 24102167
TI  - Effect of low-level laser therapy (808 nm) in skeletal muscle after resistance
      exercise training in rats.
AB  - OBJECTIVE: The aim of this study was to evaluate the effects of 808 nm laser
      applied after a resistance training protocol, on biochemical markers and the
      morphology of skeletal muscle in rats. BACKGROUND DATA: Strenuous physical
      activity results in fatigue and decreased muscle strength, impaired motor
      control, and muscle pain. Many biochemical and biophysical interventions have
      been studied in an attempt to accelerate the recovery process of muscle fatigue.
      Among these, low-level laser therapy (LLLT) has been demonstrated to be effective
      in increasing skeletal muscle performance in in vivo studies and in clinical
      trials. However, little is known about the effects of LLLT on muscle performance
      after resistance training. METHODS: Thirty Wistar rats were randomly divided into
      three groups: control group (CG), trained group (TG), and trained and laser
      irradiated group (TGL). The resistance training program was performed three times
      per week for 5 weeks, and consisted of a climbing exercise, with weights attached
      to the tail of the animal. Furthermore, laser irradiation was performed in the
      middle region of tibialis anterior (TA) muscle of both legs, after the exercise
      protocol. RESULTS: Analysis demonstrated that TGL demonstrated significantly
      reduced resting lactate level and decreased muscle glycogen depletion than the
      animals that were exercised only, and significantly increased the cross-section
      area of TA muscle fibers compared with thoseo in the other groups. CONCLUSIONS:
      These results suggest that LLLT could be an effective therapeutic approach in
      increasing muscle performance during a resistance exercise protocol.

PMID- 24102166
TI  - Effects of water flow rate on shear bond strength of orthodontic bracket bonded
      to enamel surface after Er:YAG laser ablation.
AB  - OBJECTIVE: The aim of present study was to evaluate the effect of water flow rate
      on enamel surface roughness and shear bond strength (SBS) of orthodontic brackets
      after Er:YAG laser ablation. BACKGROUND DATA: It is well known that external
      water supply is a fundamental requirement for Er:YAG laser efficiency on dental
      hard tissues. However, there is no consensus considering the water flow rate used
      during Er:YAG laser ablation. METHODS: Eighty sound human upper premolar teeth
      were used in the present study. Seventy-six teeth were assigned into four groups
      according to surface treatments. The 37% phosphoric acid-etched group served as
      the control. Er:YAG laser irradiation was performed in three subgroups with water
      flow rates of 25, 36, and 48 mL/min, respectively. All specimens were subjected
      to a SBS test. One specimen from each different surface treatment modality was
      examined by scanning electron microscopy. Kruskal-Wallis test was used to compare
      the SBS value of each group. RESULTS: Although the control group had the highest
      SBS value, statistically no significant differences were found among groups.
      CONCLUSIONS: Er:YAG laser application with a water flow rate of 48 mL/min
      produced better enamel surface alterations without any thermal damage to yield
      higher SBS values.

PMID- 24102168
TI  - Protective effect of laser phototherapy on acetylcholine receptors and creatine
      kinase activity in denervated muscle.
AB  - OBJECTIVE: This study was designed to assess the status of skeletal muscles after
      laser treatment during long-term denervation processes, by investigating changes
      in the level of acetylcholine receptors (AChR) and creatine kinase (CK) activity
      in the denervated gastrocnemius muscle of the rat. BACKGROUND DATA: Progressive
      muscle atrophy is common in patients with severe peripheral nerve injury.
      Denervated muscles can account for significant differences in the extent of AChR
      and CK activity during the denervation period. MATERIAL AND METHODS: The study
      was conducted on 96 rats: 48 that received laser treatment and 48 untreated
      controls. The gastrocnemius muscle was denervated by removing a 10 mm segment of
      the sciatic nerve. Low power laser irradiation was delivered transcutaneously to
      the right gastrocnemius muscle (HeNe continuous wave [CW] laser, 632.8 nm, 35 mW,
      30 min) for 14 consecutive days. Under general anesthesia, the rats were
      euthanized at seven time points: day 7 (n=10), day 14 (n=10), day 21 (n=10), day
      30 (n=5), day 60 (n=4), day 120 (n=5), and day 210 (n=4), with and without laser
      treatment, respectively. AChR was quantified by the (125)I-alpha-bungarotoxin. CK
      activity was measured by a specific spectrophotometric method. RESULTS: Laser
      treatment had a significant therapeutic effect on the denervated muscle during
      the first 21 days for AChR and the first 30 days for CK activity. CONCLUSIONS: In
      the early stages of muscle atrophy, laser phototherapy may preserve the
      denervated muscle by maintaining CK activity and the amount of AChR.

PMID- 24102169
TI  - Low-level laser therapy decreases renal interstitial fibrosis.

PMID- 24102170
TI  - Microfluidic biosensor for monitoring temporal variations of hemorheological and
      hemodynamic properties using an extracorporeal rat bypass loop.
AB  - In this study, we propose a novel microfluidic biosensor for monitoring
      hemorheological and hemodynamic properties using an extracorporeal rat bypass
      loop. To monitor temporal variations of biophysical properties including
      viscosity, flow rate, and pressure of rat blood, a complex fluidic network is
      established by connecting the abdominal aorta and jugular vein to an
      extracorporeal bypass loop including a flow stabilizer and a microfluidic
      biosensor. Three biophysical properties are simultaneously measured through label
      free operation and sensorless detection based on two sequential flow controls in
      the microfluidic channel. A discrete fluidic-circuit model is employed to derive
      analytical formulas for the complex fluidic network. First, to evaluate the
      measurement accuracy of the proposed method, a peristaltic pump is used as
      substitute for a rat. The flow rate and viscosity of 20% glycerin (test fluid)
      circulating within the fluidic network are measured, and then the results are
      compared with those obtained using conventional methods. The normal differences
      between two measurement methods are less than 4%. Then, the proposed method is
      used to monitor temporal variations in biophysical properties of blood
      circulating within the complex fluidic network under normal and continuous
      hemodilution conditions. Rats require at least 30 min to adapt to different
      fluidic environments. The flow rate, pressure, and hematocrit of rat blood tend
      to decrease gradually because of continuous hemodilution effect. Furthermore, the
      reduced flow rate increases blood viscosity under hemodilution condition. These
      experiments demonstrate that the proposed method can effectively monitor temporal
      variations of biophysical properties of rat blood under ex vivo conditions. 

PMID- 24102171
TI  - On the interpersonal dynamics of sexuality.
AB  - To date, theory and research on the interpersonal dynamics of sexuality is
      scarce. This is remarkable because people most often have sex in a relationship.
      To create more valid models of sexual functioning, it is important to go beyond
      the study of individual factors and take into account relational and contextual
      variables, which may act as risk and protective factors for developing,
      maintaining, and exacerbating sexual problems. This article describes theoretical
      ideas on how sexuality and relationships can be linked through motivation and
      emotion regulation. First, the sexual system is conceptualized as an emotion
      regulation device that involves a dynamic interplay between cognitive, affective,
      and motivational responses. Then, it is illustrated how partner variables,
      relationship processes, and sociorelational context may interact with these
      different responses and eventually shape how sexual emotions are generated and
      regulated. The author continues with explaining the implications of such emotion
      motivational perspective for studying determinants of sexual responding, the role
      of coregulation in tuning sexual responses in the couple, and the interrelation
      between the sexual and relational goals of both partners. Linking sexual and
      nonsexual aspects of relationships and including data of both couple members is
      necessary for a clearer insight into the nature of sexual dysfunctions. 

PMID- 24102172
TI  - Solving the paradox of stasis: squashed stabilizing selection and the limits of
      detection.
AB  - Despite the potential for rapid evolution, stasis is commonly observed over
      geological timescales-the so-called "paradox of stasis." This paradox would be
      resolved if stabilizing selection were common, but stabilizing selection is
      infrequently detected in natural populations. We hypothesize a simple solution to
      this apparent disconnect: stabilizing selection is hard to detect empirically
      once populations have adapted to a fitness peak. To test this hypothesis, we
      developed an individual-based model of a population evolving under an invariant
      stabilizing fitness function. Stabilizing selection on the population was
      infrequently detected in an "empirical" sampling protocol, because (1) trait
      variation was low relative to the fitness peak breadth; (2) nonselective deaths
      masked selection; (3) populations wandered around the fitness peak; and (4)
      sample sizes were typically too small. Moreover, the addition of negative
      frequency-dependent selection further hindered detection by flattening or even
      dimpling the fitness peak, a phenomenon we term "squashed stabilizing selection."
      Our model demonstrates that stabilizing selection provides a plausible resolution
      to the paradox of stasis despite its infrequent detection in nature. The key
      reason is that selection "erases its traces": once populations have adapted to a
      fitness peak, they are no longer expected to exhibit detectable stabilizing
      selection. 

PMID- 24102173
TI  - LnPO4 nanoparticles doped with Ac-225 and sequestered daughters for targeted
      alpha therapy.
AB  - For targeted alpha therapy (TAT) with 225Ac, daughter radioisotopes from the
      parent emissions should be controlled. Here, we report on a second-generation
      layered nanoparticle (NP) with improved daughter retention that can mediate TAT
      of lung tumor colonies. NPs of La3+, Gd3+, and 225Ac3+ ions were coated with
      additional layers of GdPO4 and then coated with gold via citrate reduction of
      NaAuCl4. MAb 201b, targeting thrombomodulin in lung endothelium, was added to a
      polyethylene glycol (dPEG)-COOH linker. The NPs:mAb ratio was quantified by
      labeling the mAb with 125I. NPs showed 30% injected dose/organ antibody-mediated
      uptake in the lung, which increased to 47% in mice pretreated with clodronate
      liposomes to reduce phagocytosis. Retention of daughter 213Bi in lung tissue was
      more than 70% at one hour and about 90% at 24 hours postinjection. Treatment of
      mice with lung-targeted 225Ac NP reduced EMT-6 lung colonies relative to cold
      antibody competition for targeting or phosphate-buffered saline injected
      controls. We conclude that LnPO4 NPs represent a viable solution to deliver the
      225Ac as an in vivo alpha generator. The NPs successfully retain a large
      percentage of the daughter products without compromising the tumoricidal
      properties of the alpha-radiation.

PMID- 24102175
TI  - Rheology of protic ionic liquids and their mixtures.
AB  - The rheological properties of five pure protic ionic liquids (ILs), ethylammonium
      nitrate (EAN), propylammonium nitrate (PAN), ethanolammonium nitrate (EtAN),
      ethylammonium formate (EAF), and dimethylethylammonium formate (DMEAF), are
      characterized and interpreted by considering the effects of both the H-bond
      network and the solvophobic nanostructure of the liquids. The results demonstrate
      that these effects are not, however, independent or simply additive. At 20 
      degrees C, EtAN has the highest zero shear viscosity of 156.1 mPa.s, followed by
      PAN (89.3 mPa.s), EAN (35.9 mPa.s), EAF (23.1 mPa.s), and DMEAF (9.8 mPa.s). The
      primary ammonium ILs behave as Newtonian fluids at low shear rates but shear thin
      at high shear. Fits to the Vogel-Fulcher-Tammann model reveal that nanostructure
      is not affected appreciably by temperature and that all the ILs studied are of
      intermediate fragility. The rheology of binary mixtures of these ILs was analyzed
      and used to demonstrate fundamental differences in the way IL cations and anions
      interact. IL mixtures containing both nitrate and formate anions resist flow more
      strongly than the pure liquids, which is a consequence of the difference in
      hydrogen bonding capacity of the anions. Mixing cations can give rise to complex
      behavior due to the offsetting effects of hydrogen bonding and solvophobic
      nanostructure formation. 

PMID- 24102174
TI  - Biological-effect modeling of radioimmunotherapy for non-hodgkins lymphoma:
      determination of model parameters.
AB  - Treatment with Tositumomab and 131I tositumomab anti-CD20 radioimmunotherapy
      (Bexxar) yields a nonradioactive antibody antitumor response (the so-called cold
      effect) and a radiation response. Numerical parameter determination by least
      squares (LS) fitting was implemented for more accurate parameter estimates in
      equivalent biological-effect calculations. METHODS: One hundred thirty-two tumors
      in 37 patients were followed using five or six SPECT/CT studies per patient,
      three each (typical) post-tracer (0.2 GBq) and post-therapy (~3 GBq) injections.
      The SPECT/CT data were used to calculate position- and time-dependent dose rates
      and antibody concentrations for each tumor. CT-defined tumor volumes were used to
      track tumor volume changes. Combined biological-effect and cell-clearance models
      were fit to tumor volume changes. Optimized parameter values determined using LS
      fitting were compared to previous fitted values that were determined by matching
      calculated to measured tumor volume changes using visual assessment. Absorbed
      dose sensitivity (alpha) and cold-effect sensitivity (lambdap) parameters were
      the primary fitted parameters, yielding equivalent biological-effect (E) values.
      RESULTS: Individual parameter uncertainties were approximately 10% and 30% for
      alpha and lambdap, respectively. LS versus previously fit parameter values were
      highly correlated, although the averaged alpha value decreased and the averaged
      lambdap value increased for the LS fits compared to the previous fits.
      Correlation of E with 2-month tumor shrinkage data was similar for the two
      fitting techniques. The LS fitting yielded improved fit quality and likely
      improved parameter estimation.

PMID- 24102176
TI  - Magnetic resonance diffusion tractography of the preterm infant brain: a
      systematic review.
AB  - AIM: Preterm birth is associated with an increased risk of adverse
      neurodevelopmental outcomes. Diffusion magnetic resonance imaging (dMRI) combined
      with tractography can be used to assess non-invasively white matter
      microstructure and brain development in preterm infants. Our aim was to conduct a
      systematic review of the current evidence obtained from tractography studies of
      preterm infants in whom MRI was performed up to term-equivalent age. METHOD:
      Databases were searched for dMRI tractography studies of preterm infants.
      RESULTS: Twenty-two studies were assessed. The most frequently assessed tracts
      included the corticospinal tract, the corpus callosum, and the optic radiations.
      The superior longitudinal fasciculus, and the anterior and superior thalamic
      radiations were investigated less frequently. A clear relationship exists between
      diffusion metrics and postmenstrual age at the time of scanning, although the
      evidence of an effect of gestational age at birth and white matter injury is
      conflicting. Sex and laterality may play an important role in the relationship
      between diffusion metrics, early clinical assessment, and outcomes.
      INTERPRETATION: Studies involving infants of all gestational ages are required to
      elucidate the relationship between gestational age and diffusion metrics, and to
      establish the utility of tractography as a predictive tool. There is a need for
      more robust acquisition and analysis methods to improve the accuracy of assessing
      development of white matter pathways.

PMID- 24102177
TI  - Biogeochemical controls on the product of microbial U(VI) reduction.
AB  - Biologically mediated immobilization of radionuclides in the subsurface is a
      promising strategy for the remediation of uranium-contaminated sites. During this
      process, soluble U(VI) is reduced by indigenous microorganisms to sparingly
      soluble U(IV). The crystalline U(IV) phase uraninite, or UO2, is the preferable
      end-product of bioremediation due to its relatively high stability and low
      solubility in comparison to biomass-associated nonuraninite U(IV) species that
      have been reported in laboratory and under field conditions. The goal of this
      study was to delineate the geochemical conditions that promote the formation of
      nonuraninite U(IV) versus uraninite and to decipher the mechanisms of its
      preferential formation. U(IV) products were prepared under varying geochemical
      conditions and characterized with X-ray absorption spectroscopy (XAS), scanning
      transmission X-ray microscopy (STXM), and various wet chemical methods. We report
      an increasing fraction of nonuraninite U(IV) species with decreasing initial U
      concentration. Additionally, the presence of several common groundwater solutes
      (sulfate, silicate, and phosphate) promote the formation of nonuraninite U(IV).
      Our experiments revealed that the presence of those solutes promotes the
      formation of bacterial extracellular polymeric substances (EPS) and increases
      bacterial viability, suggesting that the formation of nonuraninite U(IV) is due
      to a biological response to solute presence during U(VI) reduction. The results
      obtained from this laboratory-scale research provide insight into biogeochemical
      controls on the product(s) of uranium reduction during bioremediation of the
      subsurface. 

PMID- 24102178
TI  - What is the appropriate use of palliative docetaxel in castration-resistant
      prostate cancer?

PMID- 24102179
TI  - Increased C-reactive protein implies a poorer stage-specific prognosis in colon
      cancer.
AB  - BACKGROUND: To characterize the stage-specific prognostic relevance of
      preoperative systemic inflammatory response, defined by C-reactive protein (CRP),
      in colon cancer (CC) patients. MATERIAL AND METHODS: Data from CC patients
      operated on from 1998 to 2007 at three hospitals from three different Nordic
      countries were collected retrospectively from national registries, local
      databases and/or patient records. Patients with emergency surgery, infection or
      auto-immune disease were excluded. Associations between clinical or
      histopathological variables and CRP were assessed. Patients were followed from
      the date of surgery to death or end of follow-up. Disease-specific survival (DSS)
      was the main endpoint. RESULTS: In total, 525 patients with age and stage
      distributions which were representative for CC patients were included. None of
      the patients was lost to follow-up. Age, TNM Stage, WHO differentiation grade and
      right-sided tumor location significantly associated with elevated CRP values, in
      contrast to postoperative morbidity, which did not. CRP levels were found to be a
      strong prognostic factor for DSS in CC. The risk of death due to CC was augmented
      with increasing levels of CRP in every stage of operated CC. Both short- and long
      term DSS were impaired. The sub-hazard ratios for CRP-levels above 60 mg/L were
      7.37 (CI 2.65-20.5) for stage I+ II, compared to 3.29 (CI 1.30-8.29) for stage
      III and 2.24 (CI 1.16-4.35) for stage IV. CONCLUSION: Increase of CRP
      concentrations correlate with clinically relevant poorer disease-specific
      survival in each stage of CC.

PMID- 24102181
TI  - Allergic contact dermatitis in Danish children referred for patch testing - a
      nationwide multicentre study.
AB  - BACKGROUND: Although contact allergy among children was previously considered to
      be rare, data from the past decade have shown that it is common among children
      and that the prevalence may be increasing. OBJECTIVES: To describe the
      demographics of all children referred for patch testing in Denmark during 2003
      2011, to examine the frequency and relevance of positive patch test reactions,
      and to assess the most common allergens. METHODS: A retrospective analysis of the
      patch test data from the Danish National Database of Contact Allergy was
      performed. RESULTS: Of 2594 children and adolescents aged 1-17 years, 25.1% had
      one or more positive patch test reactions. The associated relevance was 66.4%.
      The most common sensitizers were metals, fragrances, and hair dyes. The frequency
      of positive patch test reactions and allergic contact dermatitis was
      significantly higher among girls. CONCLUSIONS: Allergic contact dermatitis in
      children is a significant clinical problem. Contact allergy should always be
      considered when children with recalcitrant eczema are encountered, and special
      attention should be paid to girls. Patch testing is important, and children may
      be tested with the same patch test concentrations as adults.

PMID- 24102182
TI  - Maternal use of cyclobenzaprine (Flexeril) may induce ductal closure and
      persistent pulmonary hypertension in neonates.
AB  - A full-term male infant presented shortly after birth with respiratory distress.
      An echocardiogram done within the first hour of life showed an elevated pulmonary
      artery pressure, an associated right ventricular hypertrophy without a patent
      ductus arteriosus. The patient was treated for persistent pulmonary hypertension
      with favorable response. Maternal history was unremarkable except for chronic low
      back pain treated with cyclobenzaprine (Flexeril(r)). A proposed mechanism for
      cyclobenzaprine includes inhibition of norepinephrine and serotonin reuptake,
      factors known to inhibit prostaglandin and nitric oxide. These two factors are
      the leading causes of in-utero ductal closure. This report is the first to
      indicate that cyclobenzaprine use during late pregnancy should be considered a
      potential cause of early ductal closure.

PMID- 24102180
TI  - Liver only metastatic disease in patients with metastatic colorectal cancer:
      impact of surgery and chemotherapy.
AB  - BACKGROUND: Metastatectomy in colorectal cancer (CRC) is now a standard of care
      with improved survival reported. Conversion chemotherapy has increased the
      population who are suitable for surgery. Here we assess patterns of care and
      treatment outcome in liver only metastases in South Australia using the clinical
      registry for advanced CRC. METHODS: We analysed the outcomes for patients with
      liver only metastatic involvement from the SA Metastatic CRC Database with the
      aim to investigate the role of chemotherapy on liver resection and outcome in
      comparison to liver resection only and chemotherapy without liver resection.
      Patients who had no therapy or non-surgical liver interventions were excluded for
      this analysis. RESULTS: One thousand nine hundred and eight patients were
      available for analysis, 687 (36%) had liver only metastatic disease and 455 (24%)
      had active therapy as defined. In total 54.2% (247/455) had chemotherapy alone,
      19.1% (87/455) had liver resection alone, and 26.6% (121/455) had combined
      treatment. The three-year survival for chemotherapy, resection and combined
      treatment subgroups is 19.5%, 73.8% and 73.7%, respectively. The addition of
      chemotherapy to surgery did not improve survival. Switching chemotherapy was
      associated with a poorer outcome; three-year overall survival for chemotherapy
      switch was 62.5%, compared with same regimen pre- and post-74%, and chemo post
      resection 80%. CONCLUSION: Liver only metastatic disease is common in CRC and
      patients undergoing liver resection have improved long-term survival. Survival
      for a combined approach of chemotherapy and hepatic resection is similar to
      surgery alone. Patients not suitable for surgery with liver only disease have a
      poorer prognosis highlighting the need for improved liver-directed therapies and
      attempts to covert non-resectable to resectable disease if possible.

PMID- 24102183
TI  - Transurethral microwave thermotherapy treatment of chronic urinary retention in
      patients unsuitable for surgery.
AB  - OBJECTIVE: The aim of this study was to evaluate transurethral microwave
      thermotherapy (TUMT) in the treatment of chronic urinary retention due to benign
      prostatic hyperplasia (BPH) in patients unsuitable for surgery. MATERIAL AND
      METHODS: The study enrolled 124 patients with chronic urinary retention due to
      BPH. The median age was 80 years (61-92 years). Of the enrolled patients, 77
      (62%) were assessed by an anaesthesiologist as being unsuitable for surgery owing
      to cardiac, pulmonary, neurological or other diseases. Overall, 115 patients
      (93%) had an indwelling catheter. The remaining nine patients (7%) performed
      clean intermittent self-catheterization. The treatment was performed under local
      anaesthesia in the outpatient department using the ProstaLund Coretherm Device.
      At the 6-month follow-up, the Danish version of the International Prostate
      Symptom Score (DAN-PSS), postvoiding residual volume and urinary peak flow were
      measured. Improvement in quality of life was also registered. RESULTS: The
      success of TUMT was assessed by looking at the percentage of patients relieved of
      their catheter and by the improvement in quality of life. Overall, 77% of
      patients were relieved of their catheter and 79% reported an improvement in their
      quality of life. CONCLUSION: In this study, both the median age and the
      percentage of patients unsuitable for surgery were larger than in previous
      studies. Despite this, TUMT relieved 77% of their catheter and 79% reported an
      improvement in their quality of life. This study shows that TUMT is an effective
      treatment for patients unsuitable for surgery and with chronic urinary retention.

PMID- 24102185
TI  - Development and characterization of lecithin stabilized glibenclamide
      nanocrystals for enhanced solubility and drug delivery.
AB  - Novel LNCs (lipid nanocrystals) were developed with an aim to improve the
      solubility, stability and targeting efficiency of the model drug glibenclamide
      (GLB). PEG 20000, Tween 80 and soybean lecithin were used as polymer, surfactant
      and complexing agent, respectively. GLB nanocrystals (NCs) were prepared by
      precipitation process and complexed using hot and cold melt technique. The LNCs
      were evaluated by drug loading, saturation solubility (SL), optical clarity, in
      vitro dissolution, solid state characterization, in vivo and stability analysis.
      LNCs exhibited a threefold increase in SL and a higher dissolution rate than GLB.
      The percentage dissolution efficiency was found to decrease with increase in PEG
      20000. The average particle size was in the range of 155-842 nm and zeta
      potential values tend to increase after complexation. X-ray powder diffractometry
      and differential scanning calorimetry results proved the crystallinity prevailed
      in the samples. Spherical shaped particles (<1000 nm) with a lipid coat on the
      surface were observed in scanning electron microscopy analysis. Fourier transform
      infrared results proved the absence of interaction between drug and polymer and
      stability study findings proved that LNCs were stable. In vivo study findings
      showed a decrease in drug concentration to pancreas in male Wistar rats. It can
      be concluded that LNCs are could offer enhanced solubility, dissolution rate and
      stability for poorly water soluble drugs. The targeting efficiency of LNCs was
      decreased and further membrane permeability studies ought to be carried out.

PMID- 24102186
TI  - Low-tilt monophasic and biphasic waveforms compared with standard biphasic
      waveforms in the transvenous defibrillation of ventricular fibrillation.
AB  - BACKGROUND: Commercially available implantable defibrillators utilize a high-tilt
      waveform. Studies in atrial fibrillation and transthoracic defibrillation of
      ventricular fibrillation (VF) have shown improved defibrillation efficacy using
      low-tilt (LT) waveforms. We investigated the feasibility, efficacy, and safety of
      a LT waveform in the transvenous defibrillation of VF and hypothesized that it
      would be more efficacious than standard tilted biphasic (STB) waveforms. METHODS
      AND RESULTS: The investigation was performed in four phases in a porcine model:
      an efficacy study of LT monophasic waveforms (n = 9), an efficacy study of LT
      biphasic waveforms (n = 9), a comparison study between the most successful LT
      waveforms and clinically available STB waveforms (n = 15), and a safety study (n
      = 9). A total of 1,056 shocks were delivered (phase 1: 288, phase 2: 288, phase
      3: 480). The LT biphasic 8/4-ms waveform was significantly more likely to
      successfully defibrillate than the LT monophasic and STB waveforms with an odds
      ratio of 122.3 (95% confidence interval: 32.5, 460.2, P < 0.001). The calculated
      defibrillation threshold (E50) for the LT 8/4-ms waveform was 12.7 J compared to
      43.5 J and 45.5 J for STB waveforms 6/6 ms and 8/4 ms, respectively, and 47.7 J
      for LT 12-ms waveform. The LT 8/4-ms waveform had no lasting detrimental effect
      on cardiac function, and any transient hemodynamical or biochemical changes
      observed were comparable to those observed with STB waveforms. CONCLUSION: LT
      waveforms are effective and appear safe in transvenous defibrillation in a
      porcine model of VF. The LT biphasic 8/4-ms waveform is more efficacious than
      conventional waveforms.

PMID- 24102187
TI  - Reversible quenching of a chromophore luminescence by color transition of a
      polydiacetylene.
AB  - A new reactive diacetylene molecule has been synthesized, incorporating a
      strongly luminescent chromophore, tetrazine (Tz). It readily polymerizes into the
      blue polydiacetylene (PDA) form, quenching the Tz luminescence already at
      concentrations <=1 %. The blue to red PDA transition is thermally induced in the
      solid state and the original strong Tz emission is restored. This might lead to a
      new type of detection for sensors using the PDA color transition. 

PMID- 24102184
TI  - Characterization of a novel multifunctional resveratrol derivative for the
      treatment of atrial fibrillation.
AB  - BACKGROUND AND PURPOSE: Atrial fibrillation (AF) is the most common cardiac
      arrhythmia and is associated with an increased risk for stroke, heart failure and
      cardiovascular-related mortality. Candidate targets for anti-AF drugs include a
      potassium channel K(v)1.5, and the ionic currents I(KACh) and late I(Na), along
      with increased oxidative stress and activation of NFAT-mediated gene
      transcription. As pharmacological management of AF is currently suboptimal, we
      have designed and characterized a multifunctional small molecule, compound 1
      (C1), to target these ion channels and pathways. EXPERIMENTAL APPROACH: We made
      whole-cell patch-clamp recordings of recombinant ion channels, human atrial
      I(Kur), rat atrial I(KACh), cellular recordings of contractility and calcium
      transient measurements in tsA201 cells, human atrial samples and rat myocytes. We
      also used a model of inducible AF in dogs. KEY RESULTS: C1 inhibited human peak
      and late K(v)1.5 currents, frequency-dependently, with IC50 of 0.36 and 0.11
      MUmol.L(-1) respectively. C1 inhibited I(KACh)(IC50 of 1.9 MUmol.L(-1)) and the
      Na(v)1.5 sodium channel current (IC50s of 3 and 1 MUmol.L(-1) for peak and late
      components respectively). C1 (1 MUmol.L(-1)) significantly delayed contractile
      and calcium dysfunction in rat ventricular myocytes treated with 3 nmol.L(-1) sea
      anemone toxin (ATX-II). C1 weakly inhibited the hERG channel and maintained
      antioxidant and NFAT-inhibitory properties comparable to the parent molecule,
      resveratrol. In a model of inducible AF in conscious dogs, C1 (1 mg.kg(-1))
      reduced the average and total AF duration. CONCLUSION AND IMPLICATIONS: C1
      behaved as a promising multifunctional small molecule targeting a number of key
      pathways involved in AF.

PMID- 24102188
TI  - UVA and UVB-Induced 8-Methoxypsoralen Photoadducts and a Novel Method for their
      Detection by Surface-Enhanced Laser Desorption Ionization Time-of-Flight Mass
      Spectrometry (SELDI-TOF MS).
AB  - UVA-activated psoralens are used to treat hyperproliferative skin conditions due
      to their ability to form DNA photoadducts, which impair cellular processes and
      may lead to cell death. Although UVA (320-400 nm) is more commonly used
      clinically, studies have shown that UVB (280-320 nm) activation of psoralen can
      also be effective. However, there has been no characterization of UVB-induced
      adduct formation in DNA alone. As psoralen derivatives have a greater extinction
      coefficient in the UVB region (11 800 cm(-1)  M(-1) at 300 nm) compared with the
      UVA region (2016 cm(-1)  M(-1) at 365 nm), a greater extent of adduct formation
      is expected. SELDI-TOF, a proteomic technique that combines chromatography with
      mass spectrometry, was used to detect photoadduct formation in an alternating A-T
      oligonucleotide. 8-Methoxypsoralen (8-MOP) and DNA solutions were irradiated with
      either UVA or UVB. An adduct peak was obtained with SELDI-TOF. For UVB-activated
      8-MOP, the extent of adducts was three times greater than for UVA. HPLC ESI-MS
      analysis showed that UVB irradiation yielded high levels of 3,4-monoadducts (78%
      of total adducts). UVA was more effective than UVB at conversion of 4',5'
      monoadducts to crosslinks (17% vs 4%, respectively). This report presents a
      method for comparing DNA binding efficiencies of interstrand crosslink inducing
      agents.

PMID- 24102189
TI  - Does moonlight increase predation risk? Meta-analysis reveals divergent responses
      of nocturnal mammals to lunar cycles.
AB  - The risk of predation strongly affects mammalian population dynamics and
      community interactions. Bright moonlight is widely believed to increase predation
      risk for nocturnal mammals by increasing the ability of predators to detect prey,
      but the potential for moonlight to increase detection of predators and the
      foraging efficiency of prey has largely been ignored. Studies have reported
      highly variable responses to moonlight among species, calling into question the
      assumption that moonlight increases risk. Here, we conducted a quantitative meta
      analysis examining the effects of moonlight on the activity of 59 nocturnal
      mammal species to test the assumption that moonlight increases predation risk. We
      examined patterns of lunarphilia and lunarphobia across species in relation to
      factors such as trophic level, habitat cover preference and visual acuity. Across
      all species included in the meta-analysis, moonlight suppressed activity. The
      magnitude of suppression was similar to the presence of a predator in
      experimental studies of foraging rodents (13.6% and 18.7% suppression,
      respectively). Contrary to the expectation that moonlight increases predation
      risk for all prey species, however, moonlight effects were not clearly related to
      trophic level and were better explained by phylogenetic relatedness, visual
      acuity and habitat cover. Moonlight increased the activity of prey species that
      use vision as their primary sensory system and suppressed the activity of species
      that primarily use other senses (e.g. olfaction, echolocation), and suppression
      was strongest in open habitat types. Strong taxonomic patterns underlay these
      relationships: moonlight tended to increase primate activity, whereas it tended
      to suppress the activity of rodents, lagomorphs, bats and carnivores. These
      results indicate that visual acuity and habitat cover jointly moderate the effect
      of moonlight on predation risk, whereas trophic position has little effect. While
      the net effect of moonlight appears to increase predation risk for most nocturnal
      mammals, our results highlight the importance of sensory systems and phylogenetic
      history in determining the level of risk.

PMID- 24102190
TI  - Hemorrhagic complications of thoracentesis and small-bore chest tube placement in
      patients taking clopidogrel.
AB  - RATIONALE: Clopidogrel is a commonly used antiplatelet medication. The risk of
      local hemorrhage associated with use of this drug during routine thoracentesis or
      small-bore chest tube placement is not well established. OBJECTIVES: We conducted
      a prospective cohort study to assess the risk of hemothorax in patients taking
      clopidogrel while undergoing either pleural procedure. METHODS: Twenty-five
      consecutive adult patients who were taking clopidogrel at the time they were
      offered thoracentesis or small-bore (14 Fr) chest tube placement consented to
      continue taking the drug through their procedure. A control group consisted of 50
      patients undergoing these pleural procedures who were not taking clopidogrel at
      the time they consented to undergo either procedure. All of the pleural
      procedures were performed under ultrasound guidance by an interventional
      pulmonologist or a fellow under direct faculty supervision. Hospitalized patients
      were screened for hemothorax by observing for a post-procedure drop in blood
      hemoglobin content of 2 g/dl or reaccumulation of their pleural effusion within
      24 hours of the procedure. Outpatients were called within 2 weeks after their
      procedure to determine whether they had any symptoms suggestive of hemothorax.
      MEASUREMENTS AND MAIN RESULTS: There was one case of hemothorax after
      thoracentesis in the clopidogrel group versus none in the control group. The one
      patient with hemothorax required transfusion with 2 units of packed red blood
      cells and small-bore chest tube placement, and clopidogrel was withheld. There
      were no other clinically apparent complications of either procedure. CONCLUSIONS:
      Considered in combination with other small previously published studies, this
      single-center, nonrandomized, controlled prospective cohort study suggests that
      the rate of clinically consequential hemorrhage after ultrasound-guided
      thoracentesis or chest tube placement in patients taking clopidogrel is
      sufficiently low to warrant a large, randomized clinical trial designed to
      determine the safety of performing these procedures without interrupting
      clopidogrel therapy.

PMID- 24102192
TI  - Maternal, umbilical arterial and umbilical venous 25-hydroxyvitamin D and
      adipocytokine concentrations in pregnancies with and without gestational
      diabetes.
AB  - OBJECTIVE: Gestational diabetes mellitus (GDM) has been associated with
      inflammation as well as Vitamin D insufficiency. While Vitamin D has anti
      inflammatory properties, relationships between Vitamin D and inflammatory markers
      remain unexplored in GDM. Therefore, this case--control study investigated
      adipocytokine and Vitamin D [25(OH)D] concentrations and correlations in GDM and
      control women, as well as their neonates. DESIGN/PARTICIPANTS/MEASUREMENTS:
      seventy-three women participated: 36 GDM and 37 controls. Maternal samples were
      drawn at 31 weeks. Umbilical arterial and venous samples were collected at birth.
      25(OH)D and adipocytokine concentrations were compared for GDM vs control
      maternal, umbilical arterial and venous samples. Correlations were explored
      between biochemical results, maternal and neonatal demographics. RESULTS:
      Compared with age- and weight-matched control participants, GDM women had
      significantly lower concentrations of 25(OH)D (77.3 +/- 24.3 vs 93.2 +/- 19.2
      nm/l; P = 0.009); adiponectin (17.5 +/- 11.8 vs 34.1 +/- 20.3 MUg/ml, P < 0.001);
      resistin (25.4 +/- 9.1 vs 31.9 +/- 12.1 ng/ml, P = 0.045); and plasminogen
      activator inhibitor-1 (PAI-1) 13.9 +/- 10.0 vs 21.0 +/- 12.6 ng/ml, P = 0.038),
      while delivering 1 week earlier (38.2 +/- 1.2 vs 39.5 +/- 0.9 weeks, P < 0.001).
      GDM maternal 25(OH)D concentrations positively correlated with PAI-1, IL-8 and
      TNF-alpha concentrations. Umbilical 25(OH)D concentrations were not significantly
      different in GDM vs control offspring, whereas adiponectin, resistin and PAI-1
      concentrations were significantly lower in GDM offspring. CONCLUSIONS: GDM women
      had lower 25(OH)D concentrations than controls, while neonatal umbilical
      concentrations of 25(OH)D did not differ. GDM maternal and GDM offspring had
      lower adiponectin, resistin and PAI-1 concentrations compared with controls.
      Results suggest that both GDM women and their offspring demonstrate abnormal
      adipocytokine patterns.

PMID- 24102191
TI  - L-edge X-ray absorption spectroscopy and DFT calculations on Cu2O2 species:
      direct electrophilic aromatic attack by side-on peroxo bridged dicopper(II)
      complexes.
AB  - The hydroxylation of aromatic substrates catalyzed by coupled binuclear copper
      enzymes has been observed with side-on-peroxo-dicopper(II) (P) and bis-MU-oxo
      dicopper(III) (O) model complexes. The substrate-bound-O intermediate in
      [Cu(II)2(DBED)2(O)2](2+) (DBED = N,N'-di-tert-butyl-ethylenediamine) was shown to
      perform aromatic hydroxylation. For the [Cu(II)2(NO2-XYL)(O2)](2+) complex, only
      a P species was spectroscopically observed. However, it was not clear whether
      this O-O bond cleaves to proceed through an O-type structure along the reaction
      coordinate for hydroxylation of the aromatic xylyl linker. Accurate evaluation of
      these reaction coordinates requires reasonable quantitative descriptions of the
      electronic structures of the P and O species. We have performed Cu L-edge XAS on
      two well-characterized P and O species to experimentally quantify the Cu 3d
      character in their ground state wave functions. The lower per-hole Cu character
      (40 +/- 6%) corresponding to higher covalency in the O species compared to the P
      species (52 +/- 4%) reflects a stronger bonding interaction of the bis-MU-oxo
      core with the Cu(III) centers. DFT calculations show that 10-20% Hartree-Fock
      (HF) mixing for P and ~38% for O species are required to reproduce the Cu-O
      bonding; for the P species this HF mixing is also required for an
      antiferromagnetically coupled description of the two Cu(II) centers. B3LYP (with
      20% HF) was, therefore, used to calculate the hydroxylation reaction coordinate
      of P in [Cu(II)2(NO2-XYL)(O2)](2+). These experimentally calibrated calculations
      indicate that the electrophilic attack on the aromatic ring does not involve
      formation of a Cu(III)2(O(2-))2 species. Rather, there is direct electron
      donation from the aromatic ring into the peroxo sigma* orbital of the
      Cu(II)2(O2(2-)) species, leading to concerted C-O bond formation with O-O bond
      cleavage. Thus, species P is capable of direct hydroxylation of aromatic
      substrates without the intermediacy of an O-type species.

PMID- 24102194
TI  - Quality of sexual life and its effect on marital adjustment of Turkish women in
      pregnancy.
AB  - Pregnancy is an important period of a woman's life that can affect marital
      relationships because of decrease in the sexual function. This study aimed to
      examine the effect of sexual life on the marital adjustment of 607 healthy,
      pregnant women using the self-administered Sexual Quality of Life Questionnaire
      Female and the Marital Adjustment Scale. Results showed that 30% of the pregnant
      women experienced problems during sexual intercourse and 50% had painful
      intercourse. The median total score of the Sexual Quality of Life Questionnaire
      Female for pregnant women was 35.5, and the median total score of the Marital
      Adjustment Scale was 41.0. The authors found a positive moderate level
      correlation between the sexual quality of life for women and their marital
      adjustment for being pregnant (r = 0.468, p =.001). The results imply that the
      variance in the sexual activity during the childbearing period does occur and
      pregnant women need to be assessed regularly with regards to their sexuality by
      health care providers in a professional atmosphere. 

PMID- 24102193
TI  - Design, optimization, and biological evaluation of novel keto-benzimidazoles as
      potent and selective inhibitors of phosphodiesterase 10A (PDE10A).
AB  - Our development of PDE10A inhibitors began with an HTS screening hit (1) that
      exhibited both high p-glycoprotein (P-gp) efflux ratios in rat and human and poor
      metabolic stability. On the basis of cocrystal structure of 1 in human PDE10A
      enzyme, we designed a novel keto-benzimidazole 26 with comparable PDE10A potency
      devoid of efflux liabilities. On target in vivo coverage of PDE10A in rat brain
      was assessed using our previously reported LC-MS/MS receptor occupancy (RO)
      technology. Compound 26 achieved 55% RO of PDE10A at 30 mg/kg po and covered
      PDE10A receptors in rat brain in a dose-dependent manner. Cocrystal structure of
      26 in PDE10A confirmed the binding mode of the novel scaffold. Further
      optimization resulted in the identification of keto-benzimidazole 34, which
      showed an increased in vivo efficacy of 57% RO in rats at 10 mg/kg po and an
      improved in vivo rat clearance and oral bioavailability. 

PMID- 24102195
TI  - Alterations of NMDA receptor binding in various brain regions among 6
      hydroxydopamine-induced Parkinsonian rats.
AB  - The N-methyl-d-aspartate (NMDA) system closely interacts with the dopaminergic
      system and is strongly implicated in the pathophysiological mechanisms and
      therapeutic paradigms of Parkinson's disease. This study aims to systematically
      investigate the changes of NMDA receptors in a wide range of brain structures 3
      weeks after unilateral medial forebrain bundle lesion by 6-hydroxydopamine (6
      OHDA). NMDA receptor distributions and alterations in the post-mortem rat brain
      were detected by [(3)H] MK-801 binding autoradiography. In the 6-OHDA-induced
      Parkinsonian rat model, nigrostriatal dopaminergic neuron loss significantly
      mediated the decreased [(3)H] MK-801 binding, predominantly in the hippocampus (
      22.4%, p < 0.001), caudate putamen (-14.1%, p < 0.01), accumbens nucleus (-13.8%,
      p < 0.05), cingulate cortex (-13.4%, p < 0.001), posteromedial cortical amygdala
      (-14.5%, p < 0.01) and piriform cortex (-9%, p < 0.05) compared to the controls,
      while there was a profound reduction of tyrosine hydroxylase (TH)
      immunohistochemistry in the substantia nigra pars compacta. Alterations in [(3)H]
      MK-801 in the specific brain regions related to cognitive functions may indicate
      that cognitive dysfunctions caused by 6-OHDA lesion were via the NMDA system. The
      downregulation of NMDA receptor binding in the present study provides indirect
      evidence for plasticity in the NMDA system in the rat brain. The present study
      improves our understanding of the critical roles of the NMDA receptors in
      treating neurodegenerative disorders, and implicates NMDA receptors as a novel
      therapeutic target in the treatment of Parkinson's disease. 

PMID- 24102196
TI  - The efficacy of systemic therapy for childhood and adolescent externalizing
      disorders: a systematic review of 47 RCT.
AB  - Systemic (family) therapy is a widely used psychotherapy approach. However, most
      systematic efficacy reviews have focused solely on "family-based treatment"
      rather than on the theoretic orientation "systemic therapy." We systematically
      review trials on the efficacy of systemic therapy for the treatment of childhood
      and adolescent externalizing disorders. All randomized (or matched) controlled
      trials (RCT) evaluating systemic/systems-oriented therapy in various forms
      (family, individual, group, multi-family group therapy) with child or adolescent
      index patients (0-17 years) suffering from mental disorders were identified by
      data base searches and cross-references. Inclusion criteria were as follows:
      index patient diagnosed with a DSM- or ICD-listed mental disorder, and trial
      published in any language up to the end of 2011. The RCTs were analyzed for their
      research methodology, interventions applied, and results (postintervention;
      follow-up). A total of 47 trials from the United States, Europe, and China,
      published in English, German, and Mandarin, were identified. A total of 42 of
      them showed systemic therapy to be efficacious for the treatment of attention
      deficit hyperactivity disorders, conduct disorders, and substance use disorders.
      Results were stable across follow-up periods of up to 14 years. There is a sound
      evidence base for the efficacy of systemic therapy for children and adolescents
      (and their families) diagnosed with externalizing disorders. 

PMID- 24102197
TI  - Response to a letter to the editor entitled "low serum B12 level does not mean
      vit. B12 deficiency-problems related to the diagnosis of vitamin B12 deficiency".

PMID- 24102198
TI  - Sino-orbital spelunking: stalagmite formation in fibrous dysplasia with
      dystrophic calcification.
AB  - Fibrous dysplasia (FD) involving the mid-face may be associated with cystic and
      other secondary changes that make diagnosis more difficult. We present a case of
      FD associated with a remote history of blunt facial trauma and extensive cystic
      changes involving the medial orbit and sinuses. An endoscopic exploration
      revealed "stalagmites" along the floor of the cystic cavity that were consistent
      with dystrophic calcification. This case was unusual given the degree of
      dystrophic calcification and the presence of sino-orbital stalagmites within the
      cystic cavity. Radiologic and pathologic features of the stalagmites are
      characterized.

PMID- 24102199
TI  - Engagement with meditation as a positive health trajectory: divergent narratives
      of progress in male meditators.
AB  - OBJECTIVE: Studying personal narratives can generate understanding of how people
      experience physical and mental illness. However, few studies have explored
      narratives of engagement in health positive behaviours, with none focusing on men
      specifically. Thus, we sought to examine men's experiences of their efforts to
      engage in and maintain healthy behaviours, focusing on meditation as an example
      of such behaviour. DESIGN: We recruited 30 male meditators, using principles of
      maximum variation sampling, and conducted two in-depth interviews with each,
      separated by a year. MAIN OUTCOME MEASURES: We sought to elicit men's narratives
      of their experiences of trying to maintain a meditation practice. RESULTS: We
      identified an overall theme of a 'positive health trajectory,' in particular,
      making 'progress' through meditation. Under this were six main accounts. Only two
      articulated a 'positive' message about progress: Climbing a hierarchy of
      practitioners, and progress catalysed in other areas of life. The other four
      reflected the difficulties around progress: Progress being undermined by illness;
      disappointment with progress; progress 'forgotten' (superseded by other
      concerns); and progress re-conceptualised due to other priorities. CONCLUSION:
      Men's narratives reveal the way they experience and construct their engagement
      with meditation - as an example of health behaviour - in terms of progress.

PMID- 24102200
TI  - Hexavalent chromium reduction by tartaric acid and isopropyl alcohol in Mid
      Atlantic soils and the role of Mn(III,IV)(hydr)oxides.
AB  - Chromium is a naturally occurring transition metal and a soil contaminant in the
      Cr(VI) oxidation state, but reduction of Cr(VI) to Cr(III) mitigates its
      toxicity. Tartaric acid reduces Cr(VI) via a termolecular complex with isopropyl
      alcohol and Cr(VI), but its efficacy in soils has not been demonstrated. Five Mid
      Atlantic soils from Maryland, U.S. were examined for their potential to enhance
      the reduction of Cr(VI). A control treatment (no soil +12 mM tartaric acid + 0.29
      M isopropyl alcohol) reduced 0.37 mM Cr(VI) (19%) in 99 h. Reduction was enhanced
      to 1.97 mM (99%) with addition of a Russett Ap soil horizon (fine-loamy, mixed,
      semiactive, mesic Typic Hapludult). With a half-life of 18.7 h, the rate of
      reduction of Cr(VI) with the Russett soil sample was 20 times faster than with no
      soil (371 h). Soil Mn was solubilized in this reaction and plays a role in the
      enhanced reduction of Cr(VI). Mn(III/IV)(hydr)oxide-coated quartz sand reduced
      1.24 mM (62%) Cr(VI), with all of the Mn(III,IV)(hydr)oxides solubilized. The
      addition of isopropyl alcohol and tartaric acid to soils enhances the reduction
      of Cr(VI), and this reduction is further enhanced by the catalytic behavior of
      Mn(II) from easily reducible Mn(III,IV)(hydr)oxides in soil. 

PMID- 24102201
TI  - Simultaneous telemetric monitoring of brain glucose and lactate and motion in
      freely moving rats.
AB  - A new telemetry system for simultaneous detection of extracellular brain glucose
      and lactate and motion is presented. The device consists of dual-channel, single
      supply miniature potentiostat-I/V converter, a microcontroller unit, a signal
      transmitter, and a miniaturized microvibration sensor. Although based on simple
      and inexpensive components, the biotelemetry device has been used for accurate
      transduction of the anodic oxidation currents generated on the surface of
      implanted glucose and lactate biosensors and animal microvibrations. The device
      was characterized and validated in vitro before in vivo experiments. The
      biosensors were implanted in the striatum of freely moving animals and the
      biotelemetric device was fixed to the animal's head. Physiological and
      pharmacological stimulations were given in order to induce striatal neural
      activation and to modify the motor behavior in awake, untethered animals. 

PMID- 24102202
TI  - Reference range of fetal nasal bone length between 18 and 24 weeks of pregnancy
      in an unselected Brazilian population: experience from a single service.
AB  - OBJECTIVE: To determine reference range of fetal nasal bone length (NBL) during
      the second trimester of pregnancy in a Brazilian population. METHODS: This was a
      retrospective cross-sectional study with 2681 normal singleton pregnancies
      between 18 and 24 weeks of gestation. The NBL was obtained in the mid-sagittal
      plane of the fetal face profile using the following landmarks: nasal bone,
      overlying skin and the tip of the nose. The NBL was measured by placing the
      calipers in the out-to-out position. To assess the correlation between NBL and
      gestational age (GA), polynomial equations were calculated, with adjustments by
      coefficient of determination (R(2)). RESULTS: The mean of NBL ranged from 5.72 +/
      0.87 mm at 18-18 + 6 weeks to 7.45 +/- 1.23 mm at 24-24+6 weeks of pregnancy. We
      observed a good correlation between NBL and GA, best represented by a linear
      equation: NBL = 0.080+0.276*GA (R(2 )= 0.16). CONCLUSION: We established a
      reference range of fetal NBL in the second trimester of pregnancy in a Brazilian
      population.

PMID- 24102203
TI  - Environmental versus geographical determinants of genetic structure in two
      subalpine conifers.
AB  - Alpine ecosystems are facing rapid human-induced environmental changes, and so
      more knowledge about tree adaptive potential is needed. This study investigated
      the relative role of isolation by distance (IBD) versus isolation by adaptation
      (IBA) in explaining population genetic structure in Abies alba and Larix decidua,
      based on 231 and 233 single nucleotide polymorphisms (SNPs) sampled across 36 and
      22 natural populations, respectively, in the Alps and Apennines. Genetic
      structure was investigated for both geographical and environmental groups, using
      analysis of molecular variance (AMOVA). For each species, nine environmental
      groups were defined using climate variables selected from a multiple factor
      analysis. Complementary methods were applied to identify outliers based on these
      groups, and to test for IBD versus IBA. AMOVA showed weak but significant genetic
      structure for both species, with higher values in L. decidua. Among the potential
      outliers detected, up to two loci were found for geographical groups and up to
      seven for environmental groups. A stronger effect of IBD than IBA was found in
      both species; nevertheless, once spatial effects had been removed, temperature
      and soil in A. alba, and precipitation in both species, were relevant factors
      explaining genetic structure. Based on our findings, in the Alpine region,
      genetic structure seems to be affected by both geographical isolation and
      environmental gradients, creating opportunities for local adaptation.

PMID- 24102204
TI  - The importance of atrial fibrillation burden and the origin of device-tailored
      anticoagulation.
AB  - The current paradigm for anticoagulation in patients with atrial fibrillation is
      based upon clinical risk factors for stroke without reference to the frequency or
      duration (i.e., burden) of atrial fibrillation episodes. In the last decade,
      increasing evidence derived from device-based surveillance of atrial fibrillation
      has suggested that in some patients the burden of atrial fibrillation may be
      associated with thromboembolic risk. The development of rapidly acting oral
      anticoagulants and devices with remote monitoring capability has allowed the
      testing of a strategy of tailored or "pill-in-the-pocket" anticoagulation based
      upon atrial fibrillation burden. 

PMID- 24102205
TI  - Arterial stiffness in patients with lower urinary tract symptoms.

PMID- 24102206
TI  - Enhanced visible-photocatalytic activity of anodic TiO2 nanotubes film via
      decoration with CuInSe2 nanocrystals.
AB  - The fabrication and photocatalytic properties of visible-light driven
      CuInSe2/TiO2 heterojunction films are reported. CuInSe2 nanoparticles (NCs) were
      synthesized using a solvothermal method and then decorated onto self-organized
      anodic TiO2 nanotube (NT) arrays through an electrophoretic deposition process,
      forming a CuInSe2 NC/TiO2 NT hetero-structure film. An increase in deposition
      time produced an increased amount of CuInSe2 NCs loaded onto the TiO2 NT arrays,
      expanding the light-absorption range of the CuInSe2 NCs/TiO2 NTs film from 400 nm
      to 700 nm. Photocatalytic degradation results show that activities of the CuInSe2
      NCs/TiO2 NTs films were significantly enhanced compared to that of pure TiO2 NTs
      (degradation rate constant k increased from 3 * 10(-3) min(-1) to >1 * 10(-2)
      min(-1)). Particularly, the CuInSe2 NCs/TiO2 NTs with 50 min electrophoretic
      deposition show the highest degradation rate, k = 1.6 * 10(-2) min(-1) (more than
      5 times greater than that of the pure TiO2 NTs film), due to optimization of
      CuInSe2 NCs loading and a well-maintained open TiO2 tube-mouth configuration. 

PMID- 24102207
TI  - Nanovoid formation and annihilation in gallium nanodroplets under lithiation
      delithiation cycling.
AB  - The irreversible chemomechanical degradation is a critical issue in the
      development of high-capacity electrode materials for the next-generation lithium
      (Li)-ion batteries. Here we report the self-healing behavior of gallium
      nanodroplets (GaNDs) under electrochemical cycling at room temperature, observed
      with in situ transmission electron microscopy (TEM). During lithiation, the GaNDs
      underwent a liquid-to-solid phase transition, forming a crystalline phase (LixGa)
      with ~160% volume expansion. Owing to the uneven Li flow during lithiation, the
      fully lithiated GaNDs exhibited highly distorted morphologies. Upon delithiation,
      the reverse phase transition occurred, accompanied with the nucleation and growth
      of a nanosized void. After the GaNDs were fully delithiated, the nanovoid
      gradually annihilated. Our analysis, along with phase field modeling and
      experimental measurements of the void growth and annihilation, provides
      mechanistic insights into the void formation and annihilation mechanism. The
      GaNDs may function as an effective healing agent in durable composite electrodes
      for high-performance Li-ion batteries, wherein active components, such as Si, are
      susceptible to fracture.

PMID- 24102208
TI  - State of the art and future directions in nanomedicine for tuberculosis.
AB  - INTRODUCTION: Tuberculosis (TB) ranks the second leading cause of death from an
      infectious disease worldwide. However, treatment of TB is affected by poor
      patient compliance due to the requirement for daily drug administration, for
      lengthy periods of time, often with severe drug-induced side effects.
      Nanomedicines have the potential to improve treatment outcomes by providing
      therapies with reduced drug doses, administered less frequently, under shortened
      treatment durations. AREAS COVERED: In this article, we present the
      pathophysiology of the disease, focusing on pulmonary TB and the characteristics
      of drugs used in treatment and discuss the application of nanomedicines within
      this scope. We also discuss new formulation approaches for TB nanomedicines and
      directions for future research. EXPERT OPINION: Nanomedicines have the potential
      to improve TB treatment outcomes. New approaches such as nanoparticle systems
      able to impact the immune response of macrophages and deliver drug
      intracellularly, as well as the use of polymer-drug conjugates for drug delivery,
      are likely to play an important role in TB nanomedicines in future. However,
      further research is required before TB nanomedicines can be translated to the
      clinic.

PMID- 24102209
TI  - Mineralizing angiopathy with infantile basal ganglia stroke after minor trauma.
AB  - AIMS: The objective of this study was to describe a cohort of infants with basal
      ganglia stroke associated with mineralization in the lenticulostriate arteries
      and their clinical outcomes. METHOD: Subcortical strokes occurring in infants
      during the study period were categorized as arterial ischaemic, venous, or
      haemorrhagic. A cohort of infants with basal ganglia infarcts and associated
      mineralization of lenticulostriate arteries were identified. This group was
      analysed for possible aetiological factors, clinical course, and recurrence rate
      of the stroke. RESULTS: Of 23 infants with basal ganglia arterial ischaemic
      stroke, 22 (16 males, six females; mean age 11mo [+/-SD 4.8mo]) were found to
      have lenticulostriate artery mineralization. Twenty infants presented with
      hemiparesis and two presented with recurrent episodes of hemidystonia. Eighteen
      infants had a history of minor trauma before onset of stroke. No other
      predisposing factors were identified in this cohort. There were no demonstrable
      causes for vascular and soft tissue calcification. The mean follow-up was 11
      months, during which five infants experienced stroke recurrence. Of the 17
      infants who did not experience a recurrent stroke, eight exhibited complete
      neurological recovery, and nine had mild residual hemiparesis. INTERPRETATION:
      Acute basal ganglia stroke after minor trauma associated with mineralization of
      lenticulostriate arteries in infants is a distinct clinicoradiological entity.
      Investigations for prothrombotic states and vasculopathies are normal. Although
      neurological outcomes in most children are good, trauma is a risk factor for
      recurrence of stroke.

PMID- 24102210
TI  - A Pseudomonas syringae diversity survey reveals a differentiated phylotype of the
      pathovar syringae associated with the mango host and mangotoxin production.
AB  - Pseudomonas syringae pv. syringae, the causal agent of bacterial apical necrosis
      (BAN) in mango crops, has been isolated in different mango-producing areas
      worldwide. An extensive collection of 87 P. syringae pv. syringae strains
      isolated from mango trees affected by BAN from different countries, but mainly
      from Southern Spain, were initially examined by repetitive sequence-based
      polymerase chain reaction (rep-PCR) to analyze the genetic diversity with an
      epidemiological aim. rep-PCR was powerful in assessing intrapathovar distribution
      and also allowing clustering of the P. syringae pv. syringae strains isolated
      from mango, depending on the isolation area. A clear pattern of clustering was
      observed for all the P. syringae pv. syringae strains isolated from mango
      distinct from strains from other hosts, including strains for the same
      geographical regions as the mango isolates. For this reason, a representative
      group of 51 P. syringae pv. syringae strains isolated from mango and other hosts,
      as well as some P. syringae strains from other pathovars, were further
      characterized to determine their possible genetic, phenotypic, and phylogenetic
      relationships. Similar to the rep-PCR results, the randomly amplified polymorphic
      DNA PCR (RAPD-PCR) and catabolic diversity analysis using the Biolog GN2 profile
      grouped 90% of the mango isolates together in a unique cluster. Interestingly,
      the majority of P. syringae pv. syringae strains isolated from mango produced
      mangotoxin. The analysis of the phylogenetic distribution using the multilocus
      sequence typing analysis strongly supports the existence of a differentiated
      phylotype of the pathovar syringae mainly associated with the mango host and
      characterized by the mangotoxin production.

PMID- 24102211
TI  - Effect of climate on the distribution of Fusarium spp. causing crown rot of wheat
      in the Pacific Northwest of the United States.
AB  - Fusarium crown rot (FCR) is one of the most widespread root and crown diseases of
      wheat in the Pacific Northwest (PNW) of the United States. Our objectives were to
      characterize crown rot severity and distribution throughout the PNW by conducting
      a survey of 210 fields covering the diverse dryland wheat-producing areas of
      Washington and Oregon and to utilize a factor analysis statistical approach to
      determine the effects of climate and geography on species distribution and
      disease severity. Climatic variables were based on 30-year averages and 2008 and
      2009 separately (the 2 years of the survey). Mean annual temperature, mean
      temperature in the coldest month, mean temperature in the warmest month, mean
      annual precipitation, snowfall, elevation, soil type, and cropping intensity were
      highly intercorrelated. The factor analysis of the climate variables resulted in
      the development of two latent factors that could be used as predictor variables
      in logistic regression models for the presence or absence of Fusarium spp. and of
      FCR disease scores. Isolates of Fusarium spp. were recovered from 99% of 105
      fields sampled in 2008 and 97% of fields in 2009. There were differences between
      years for responses of FCR and nodes scores, and isolations of Fusarium
      pseudograminearum with more significant results in 2008, due to warmer drier
      weather. Results of the factor analysis showed that the distribution of F.
      pseudograminearum occurred in a greater frequency in areas of the PNW at lower
      elevations with lower moisture and higher temperatures in 2008, whereas F.
      culmorum occurred in greater frequency in areas at higher elevations with
      moderate to high moisture and cooler temperatures consistently across both years.
      Disease scores increased with increasing levels of factors 1 (primarily
      temperature) and 2 (primarily precipitation). Both the frequency of pathogen
      species and disease scores were influenced by the year, indicating that soilborne
      pathogens are responsive to short-term changes in environment. This factor
      analysis approach can be utilized in studies to determine the effects of climate
      and other environmental (soil, cropping system, and so on) factors on the
      distribution and severity of root diseases.

PMID- 24102212
TI  - Cost and quality of life in patients with severe chronic hand eczema refractory
      to standard therapy with topical potent corticosteroids.
AB  - BACKGROUND: Little is known about the socio-economic burden of severe chronic
      hand eczema in patients refractory to treatment with potent corticosteroids.
      OBJECTIVES: To estimate the socio-economic burden of severe chronic hand eczema
      refractory to potent topical corticosteroids, and to establish an algorithm for
      the estimation of the health-related quality of life EuroQol five-dimensional (EQ
      5D) utility index from the Dermatology Life Quality Index (DLQI) summary score.
      METHODS: A multicentre cost of illness study was conducted, adopting the societal
      perspective. Adult patients with severe and refractory chronic hand eczema were
      enrolled. Direct (e.g. drug treatment and travel) and indirect (i.e. loss of
      productivity) mean costs/patient-month were estimated. Health-related quality of
      life was assessed with the EQ-5D and DLQI questionnaires. An ordinary least
      square regression model was used to investigate relationships between health
      related quality of life scores. RESULTS: One hundred and four valid patients
      (mean age 44.5 years, 39.4% male) participated. Overall mean costs were
      ?418.3/patient-month: loss of productivity contributed 43.7%, followed by
      hospitalization (16.1%) and travel (10.3%). Health-related quality of life scores
      were, on average, 0.50 (EQ-5D utility) and 11.3 (DLQI). Utility and DLQI summary
      were significantly related to each other. CONCLUSIONS: Wellbeing and loss of
      productivity are the most important consequences in these patients. Appropriate
      treatment is necessary to improve patient health and productivity, which will
      contribute to reducing societal costs.

PMID- 24102213
TI  - How does dysautonomia influence the outcome of traumatic brain injured patients
      admitted in a neurorehabilitation unit?
AB  - BACKGROUND: Patients surviving severe traumatic brain injury (TBI) may suffer
      from symptoms presumed to be related to an excessive sympathetic production known
      as paroxysmal sympathetic hyperactivity (PSH). While this condition is more
      common in the acute phase, prognosis is less clear in rehabilitation settings.
      AIM: The goal of this study is to describe the functional status of patients with
      PSH admitted in a rehabilitation hospital and to determine its prognostic
      influence during rehabilitation. METHODS: A cohort study was undertaken of all
      the patients admitted in a neurorehabilitation hospital suffering from PSH.
      Functional outcomes were reported according to the Glasgow outcome scale-extended
      (GOSE), the Disability Rating Scale (DRS) and the Functional Independence Measure
      (FIM). RESULTS: Thirteen out of 39 patients suffered symptoms compatible with
      PSH. Neuroimaging of PSH patients showed more diffuse lesions. The FIM at
      admission was lower in the PSH group who was transferred for rehabilitation at an
      earlier stage. At discharge no differences were seen using the FIM, DRS and GOS
      E. CONCLUSIONS: Functional status is similar and PSH does not appear to influence
      recovery during the rehabilitation, although PSH patients are more likely to
      undergo psychoactive medications and special care is needed to approach their
      caregivers that perceive PSH as a complication for rehabilitation.

PMID- 24102215
TI  - Maternal, social and abiotic environmental effects on growth vary across life
      stages in a cooperative mammal.
AB  - Resource availability plays a key role in driving variation in somatic growth and
      body condition, and the factors determining access to resources vary considerably
      across life stages. Parents and carers may exert important influences in early
      life, when individuals are nutritionally dependent, with abiotic environmental
      effects having stronger influences later in development as individuals forage
      independently. Most studies have measured specific factors influencing growth
      across development or have compared relative influences of different factors
      within specific life stages. Such studies may not capture whether early-life
      factors continue to have delayed effects at later stages, or whether social
      factors change when individuals become nutritionally independent and adults
      become competitors for, rather than providers of, food. Here, we examined
      variation in the influence of the abiotic, social and maternal environment on
      growth across life stages in a wild population of cooperatively breeding
      meerkats. Cooperatively breeding vertebrates are ideal for investigating
      environmental influences on growth. In addition to experiencing highly variable
      abiotic conditions, cooperative breeders are typified by heterogeneity both among
      breeders, with mothers varying in age and social status, and in the number of
      carers present. Recent rainfall had a consistently marked effect on growth across
      life stages, yet other seasonal terms only influenced growth during stages when
      individuals were growing fastest. Group size and maternal dominance status had
      positive effects on growth during the period of nutritional dependence on carers,
      but did not influence mass at emergence (at 1 month) or growth at independent
      stages (>4 months). Pups born to older mothers were lighter at 1 month of age and
      subsequently grew faster as subadults. Males grew faster than females during the
      juvenile and subadult stage only. Our findings demonstrate the complex ways in
      which the external environment influences development in a cooperative mammal.
      Individuals are most sensitive to social and maternal factors during the period
      of nutritional dependence on carers, whereas direct environmental effects are
      relatively more important later in development. Understanding the way in which
      environmental sensitivity varies across life stages is likely to be an important
      consideration in predicting trait responses to environmental change.

PMID- 24102216
TI  - Arsenic scavenging by aluminum-substituted ferrihydrites in a circumneutral pH
      river impacted by acid mine drainage.
AB  - Ferrihydrite (Fh) is a nanocrystalline ferric oxyhydroxide involved in the
      retention of pollutants in natural systems and in water-treatment processes. The
      status and properties of major chemical impurities in natural Fh is however still
      scarcely documented. Here we investigated the structure of aluminum-rich Fh, and
      their role in arsenic scavenging in river-bed sediments from a circumneutral
      river (pH 6-7) impacted by an arsenic-rich acid mine drainage (AMD). Extended X
      ray absorption fine structure (EXAFS) spectroscopy at the Fe K-edge shows that Fh
      is the predominant mineral phase forming after neutralization of the AMD, in
      association with minor amount of schwertmannite transported from the AMD. TEM
      EDXS elemental mapping and SEM-EDXS analyses combined with EXAFS analysis
      indicates that Al(3+) substitutes for Fe(3+) ions into the Fh structure in the
      natural sediment samples, with local aluminum concentration within the 25-30 +/-
      10 mol %Al range. Synthetic aluminous Fh prepared in the present study are found
      to be less Al-substituted (14-20 +/- 5 mol %Al). Finally, EXAFS analysis at the
      arsenic K-edge indicates that As(V) form similar inner-sphere surface complexes
      on the natural and synthetic Al-substituted Fh studied. Our results provide
      direct evidence for the scavenging of arsenic by natural Al-Fh, which emphasize
      the possible implication of such material for scavenging pollutants in natural or
      engineered systems. 

PMID- 24102217
TI  - The sugar 3-deoxy-d-manno-oct-2-ulosonic acid (Kdo) as a characteristic component
      of bacterial endotoxin -- a review of its biosynthesis, function, and placement
      in the lipopolysaccharide core.
AB  - The sugar 3-deoxy-d-manno-oct-2-ulosonic acid (Kdo) is a characteristic component
      of bacterial lipopolysaccharide (LPS, endotoxin). It connects the carbohydrate
      part of LPS with C6 of glucosamine or 2,3-diaminoglucose of lipid A by acid
      labile alpha-ketosidic linkage. The number of Kdo units present in LPS, the way
      they are connected, and the occurrence of other substituents (P, PEtn, PPEtn,
      Gal, or beta-l-Ara4N) account for structural diversity of the inner core region
      of endotoxin. In a majority of cases, Kdo is crucial to the viability and growth
      of bacterial cells. In this paper, the biosynthesis of Kdo and the mechanism of
      its incorporation into the LPS structure, as well as the location of this unique
      component in the endotoxin core structures, have been described. 

PMID- 24102214
TI  - Prostamide F(2) alpha receptor antagonism combined with inhibition of FAAH may
      block the pro-inflammatory mediators formed following selective FAAH inhibition.
AB  - BACKGROUND AND PURPOSE: Prostamides are lipid mediators formed by COX-2-catalysed
      oxidation of the endocannabinoid anandamide and eliciting effects often opposed
      to those caused by anandamide. Prostamides may be formed when hydrolysis of
      anandamide by fatty acid amide hydrolase (FAAH) is physiologically,
      pathologically or pharmacologically decreased. Thus, therapeutic benefits of FAAH
      inhibitors might be attenuated by concomitant production of prostamide F2 alpha .
      This loss of benefit might be minimized by compounds designed to selectively
      antagonize prostamide receptors and also inhibiting FAAH. EXPERIMENTAL APPROACH:
      Inhibition of FAAH by a series of selective antagonists of prostamide receptors,
      including AGN 204396, AGN 211335 and AGN 211336, was assessed using rat, mouse
      and human FAAH in vitro, together with affinity for human recombinant CB1 and CB2
      receptors. Effects in vivo were measured in a model of formalin-induced
      inflammatory pain in mice. KEY RESULTS: The prostamide F2 alpha receptor
      antagonists were active against mouse and rat FAAH in the low MUM range and
      behaved as non-competitive and plasma membrane-permeant inhibitors. AGN 211335,
      the most potent inhibitor of rat FAAH (IC50  = 1.2 MUM), raised exogenous
      anandamide levels in intact cells and also bound to cannabinoid CB1 receptors.
      Both AGN 211335 and AGN 211336 (0.25-1 mg.kg(-1) , i.p.) inhibited the formalin
      induced nociceptive response in mice. CONCLUSIONS AND IMPLICATIONS: Synthetic
      compounds with indirect agonist activity at cannabinoid receptors and antagonist
      activity at prostamide receptors can be developed. Such compounds could be used
      as alternatives to selective FAAH inhibitors to prevent the possibility of
      prostamide F2 alpha -induced inflammation and pain. LINKED ARTICLES: This article
      is part of a themed section on Cannabinoids 2013. To view the other articles in
      this section visit http://dx.doi.org/10.1111/bph.2014.171.issue-6.

PMID- 24102218
TI  - Development of a PCR assay for rapid detection of Cronobacter spp. from food.
AB  - The occurrence of outbreaks of necrotizing meningitis caused by Cronobacter spp.
      in neonates highlights the need for rapid detection and accurate identification
      of this pathogenic species. The gold standard for isolation and identification of
      Cronobacter spp. from powdered infant formula is time consuming and labor
      intensive. The gyrB gene that encodes the B subunit of DNA gyrase (topoisomerase
      type II) was found to be suitable for the identification of Cronobacter spp. A
      region of the gyrB gene of 38 Cronobacter spp. strains and 5 Enterobacter spp.
      strains was amplified and sequenced, and a pair of primers was designed and
      synthesized based on the sequence of the gyrB gene. A polymerase chain reaction
      (PCR) system was developed and optimized to detect Cronobacter spp. The PCR assay
      amplified a 438 bp DNA product from all 38 Cronobacter spp. strains tested but
      not from 34 other bacteria. The detection limit was 1.41 pg/PCR (equivalent 282
      genomic copies) when the genomic DNA of Cronobacter sakazakii ATCC 29544 was 10
      fold diluted. Infant formula powders from 3 different commercial brands were
      inoculated with strains ATCC 29544 at a level of 56 colony-forming units, and the
      target fragment were produced after samples were enriched for 6 h at 37  degrees
      C. Twenty-five food samples were evaluated by the PCR assay and the conventional
      method. A PCR product of the expected size was obtained from 3 samples; however,
      Cronobacter spp. strains were isolated from only 2 samples by the conventional
      method. This method is a useful tool for rapid identification of Cronobacter spp.
      in food and potentially environmental samples. 

PMID- 24102219
TI  - Probiotic treatment by indigenous bacteria decreases mortality without disturbing
      the natural microbiota of Salvelinus fontinalis.
AB  - Next-generation sequencing is revealing the complex interactive networks of host
      bacteria interactions, as it is now possible to screen in detail the microbiota
      harbored by a host. This study investigated the influence of a probiotic
      treatment on the survival and microbiota of brook charr (Salvelinus fontinalis),
      focusing on its disturbance of the natural microbiota (dysbiosis). The results
      indicated that an indigenous probiotic strain (identified as Rhodococcus sp.)
      colonized neither the fish skin mucus nor the water following the probiotic
      treatment. Instead, the probiotic strain was detected only in the biofilm of the
      test tank. Nevertheless, a substantial beneficial effect of the probiotic
      treatment was observed: the population of the pathogen Flavobacterium
      psychrophilum decreased in the treated tank water. This study clearly shows that
      the indigenous strain chosen for the probiotic treatment did not disturb the
      natural fish skin mucus microbiota but acted directly through the production
      system to control the growth of the pathogen and, as a consequence, to enhance
      fish survival. 

PMID- 24102220
TI  - Antimicrobial susceptibilities and distribution of sequence types of Neisseria
      gonorrhoeae isolates in Canada: 2010.
AB  - The monitoring of antimicrobial susceptibilities in Neisseria gonorrhoeae
      isolates and characterization of N. gonorrhoeae multiantigen sequence types (NG
      MAST, ST) provide important surveillance data as resistance rates continue to
      rise. A total of 2970 N. gonorrhoeae isolates were collected by Canadian
      provincial public health laboratories in 2010, and 1233 were submitted to the
      National Microbiology Laboratory for testing. The NG-MAST and minimum inhibitory
      concentration (MIC) by agar dilution were determined for each isolate. Of the
      2970 isolates, 25.1% were resistant to penicillin, 34.6% resistant to
      tetracycline, 31.5% resistant to erythromycin, 35.9% resistant to ciprofloxacin,
      and 1.2% resistant to azithromycin. Decreased susceptibility to cefixime (MIC >=
      0.25 mg/L) and ceftriaxone (MIC >= 0.125 mg/L) was identified in 3.2% and 7.3% of
      the isolates, respectively. The most common STs found in Canada were ST1407
      (13.3%), ST3150 (11.3%), and ST3158 (9.0%), with 249 different STs identified
      among the isolates. Within the ST1407 group, 19.5% and 43.3% isolates have
      decreased susceptibility to cefixime and ceftriaxone, respectively. ST1407, the
      most prevalent NG-MAST in Canada in 2010, has been associated with high-level
      ceftriaxone MICs and with cefixime treatment failure cases worldwide.
      Identification and monitoring of STs and corresponding antimicrobial resistance
      profiles may be useful in surveillance programs and be used to inform public
      health actions. 

PMID- 24102221
TI  - Characterization of enriched aerotolerant cellulose-degrading communities for
      biofuels production using differing selection pressures and inoculum sources.
AB  - Ethanol production from direct cellulose fermentation has mainly been described
      as a strictly anaerobic process. The use of air-tolerant organisms or consortia
      for this process would reduce the need for prereduction of the medium and also
      permit continuous feed of aerobic feedstock. To this end, moderately thermophilic
      (60  degrees C) consortia of fermentative, cellulolytic bacteria were enriched
      from 3 distinct environments (manure, marsh, and rotten wood) from a farm in
      southeast Saskatchewan, Canada. Community phenotypic and metabolic profiles were
      characterized. Selection methods included direct plating under an aerobic
      atmosphere and repeated passaging; the methods were designed to select for
      robust, stable aerotolerant cellulose-degrading communities. Several of the
      isolated communities exhibited an increase in total cellulose degradation and
      total ethanol yield when compared with a monoculture of Clostridium thermocellum
      DSMZ 1237. Owing to stringent selection conditions, low diversity enrichments
      were found, and many appeared to be binary cultures via density gradient gel
      electrophoresis analysis. On the basis of 16S rRNA gene sequencing, aerobic
      conditions selected for a mix of organisms highly related to C. thermocellum and
      Geobacillus species, while anaerobic conditions led to the development of
      consortia containing strains related to C. thermocellum with strains from either
      the genus Geobacillus or the genus Thermoanaerobacter. The presence of a
      Geobacillus-like species appeared to be a prerequisite for aerotolerance of the
      cellulolytic enrichments, a highly desired phenotype in lignocellulosic
      consolidated bioprocessing. 

PMID- 24102222
TI  - Lactobacillus rhamnosus CRL1505 beneficially modulates the immuno-coagulative
      response after pneumococcal infection in immunocompromised malnourished mice.
AB  - This work evaluated the effect of orally or nasally administered Lactobacillus
      rhamnosus CRL1505 on the resistance of immunocompromised protein-malnourished
      mice to pneumococcal infection. In particular, we aimed to gain knowledge of the
      mechanism involved in the immunomodulatory effect of L. rhamnosus CRL1505 in
      malnourished hosts by evaluating its impact on the immuno-coagulative response.
      Malnutrition significantly increased lung tissue damage caused by Streptococcus
      pneumoniae infection. Lung damage was associated with a deregulated activation of
      coagulation and an altered inflammatory response. Pneumococcal colonization of
      lung and bacteremia were significantly reduced (p < 0.05) in malnourished mice
      receiving the CRL1505 strain. Moreover, mice repleted with supplemental L.
      rhamnosus CRL1505 showed the least alteration of the alveolar-capillary barrier
      and cell damage in lungs after the infectious challenge, especially when the
      CRL1505 strain was administered by nasal route. Besides, mice treated with L.
      rhamnosus CRL1505 showed an improved respiratory innate immune response and a
      lower activation of coagulation. The results of this work indicate that L.
      rhamnosus CRL1505 is able to beneficially modulate the inflammation-coagulation
      interaction after respiratory infections in malnourished hosts. 

PMID- 24102223
TI  - Profiles of Mycobacterium communities under polycyclic aromatic hydrocarbon
      contamination stress in the Shenfu Irrigation Area, northeast China.
AB  - Indigenous Mycobacterium communities play an important role in the degradation of
      polycyclic aromatic hydrocarbons (PAHs), but little is known about Mycobacterium
      distribution in situ at PAH-contaminated sites. In this study, the diversity and
      distribution of Mycobacterium communities were investigated in sediments and
      soils at sites upstream, midstream, and downstream of an oil-sewage irrigation
      channel, using denaturing gradient gel electrophoresis (DGGE). The results show
      that heavy PAH contamination in upstream sites negatively affected Mycobacterium
      community diversity compared with midstream and downstream sites in all 3 sample
      types (sediments, corn field soils, and rice field soils). There was a
      correlation between the distribution of Mycobacterium communities and PAH
      contamination, as indicated by canonical correspondence analysis. Mycobacterium
      diversity and distribution was found to vary between the 3 sample types. 

PMID- 24102224
TI  - A 4-year study of avian influenza virus prevalence and subtype diversity in ducks
      of Newfoundland, Canada.
AB  - The island of Newfoundland, Canada, is at the eastern edge of North America and
      has migratory bird connections with the continental mainland as well as across
      the North Atlantic Ocean. Here, we report a 4-year avian influenza virus (AIV)
      epidemiological study in ducks in the St. John's region of Newfoundland. The
      overall prevalence of AIV detection in ducks during this study was 7.2%, with
      American Black Ducks contributing the vast majority of the collected samples and
      the AIV positives. The juvenile ducks showed a significantly higher AIV detection
      rate (10.6%) compared with adults (3.4%). Seasonally, AIV prevalence rates were
      higher in the autumn (8.4%), but positives were still detected in the winter
      (4.6%). Preliminary serology tests showed a high incidence of previous AIV
      infection (20/38, 52.6%). A total of 43 viruses were characterized for their HA
      NA or HA subtypes, which revealed a large diversity of AIV subtypes and little
      recurrence of subtypes from year to year. Investigation of the movement patterns
      of ducks in this region showed that it is a largely non-migratory duck
      population, which may contribute to the observed pattern of high AIV subtype
      turnover. Phylogenetic analysis of 4 H1N1 and one H5N4 AIVs showed these viruses
      were highly similar to other low pathogenic AIV sequences from waterfowl in North
      America and assigned all gene segments into American-avian clades. Notably, the
      H1N1 viruses, which were identified in consecutive years, possessed homologous
      genomes. Such detection of homologous AIV genomes across years is rare, but
      indicates the role of the environmental reservoir in viral perpetuation. 

PMID- 24102225
TI  - The temporal bone microdissection of miniature pigs as a useful large animal
      model for otologic research.
AB  - CONCLUSION: Compared with traditional animal models, the miniature pig may be a
      better model for biomedical research because its morphology has many similarities
      with that of humans. OBJECTIVE: To investigate the suitability of the miniature
      pig as an animal model for otological research as regards morphology. METHODS:
      Microdissection of the temporal bone of 10 miniature pigs was performed and
      recorded on photographs. RESULTS: The morphology and measurements of the
      external, middle, and inner ear, and the lateral recess of the miniature pigs
      were completed by microdissection. The temporal bone structures, including the
      external, middle, inner ear, and the lateral recess, were similar in the
      miniature pig and humans.

PMID- 24102227
TI  - Vibrant Soundbridge implantation via the third window in two Chinese patients
      with severe bilateral congenital aural atresia.
AB  - CONCLUSION: In patients with undeveloped vestibular/oval windows and inaccessible
      round windows, Vibrant Soundbridge (VSB) implantation performed by placing the
      transducer into a reconstructed window on the inner tympanum wall demonstrated
      significant improvement in hearing and verbal communication ability. OBJECTIVE:
      To report our surgical experience with new placement of the VSB in pediatric
      patients with undeveloped vestibular windows, inaccessible round windows, and
      severe bilateral congenital aural atresia (CAA). METHODS: In two patients with
      bilateral CAA selected for middle ear implantation, CT scans revealed severe
      middle ear malformation including inaccessible round windows, absence of
      vestibular/oval windows, and abnormal facial nerve anatomy. The transducer of the
      VSB was implanted into a 'window' drilled at the inner tympanum wall in both
      patients. RESULTS: The surgery was successful. Pure-tone air conduction
      thresholds across the frequencies of 0.25-8 Hz were improved by 35 dB
      (preoperation, 69.2 dB; postactivation, 34 dB) in patient 1 and 46.6 dB
      (preoperation, 75.8 dB; postactivation, 24.2 dB) in patient 2. Normal hearing
      thresholds were achieved in the range of 1-8 kHz in both patients. A sentence
      recognition rate of up to 100% (65 dB SPL in a quiet room) was attained by both
      patients after surgery and VSB activation at 3 months postoperatively.

PMID- 24102226
TI  - Vestibular evoked myogenic potential according to middle ear condition in chronic
      otitis media with tympanic membrane perforation.
AB  - CONCLUSION: Vestibular evoked myogenic potential (VEMP) function results can vary
      between individuals with different middle ear conditions. Therefore, by analyzing
      VEMP results after paper patching, we can predict the condition of the middle ear
      in chronic otitis media (COM) patients. OBJECTIVES: VEMP responses decrease with
      impairment of sound transmission, such as in conductive hearing loss (CHL). COM
      with tympanic membrane (TM) perforation is a common disorder that causes various
      degrees of CHL. The aim of this study was to evaluate and clarify the VEMP
      responses in patients with COM with different middle ear pathology. METHODS: This
      study included 50 patients with unilateral COM with TM perforation. Initial pure
      tone audiometry (PTA) and VEMP responses were recorded. After paper patching, PTA
      and VEMP were re-performed. Each VEMP response was compared with those of the
      healthy controls. Moreover, VEMP responses between pre- and post-paper patching
      were compared. RESULTS: There was a positive correlation between normalizing of
      VEMP parameters, such as p13 and VEMP asymmetry ratio (VAR), and reduction of air
      bone gap in patients with COM after paper patching. The VEMP response in patients
      with COM with intact ossicle and clean mucosa was more normalized compared with
      those in patients with COM with different middle ear conditions.

PMID- 24102228
TI  - Anxiety disorders in patients with implantable cardioverter defibrillators:
      frequency, course, predictors, and patients' requests for treatment.
AB  - OBJECTIVES: To determine (1) the frequency and course of anxiety disorders in
      patients with implantable cardioverter defibrillators (ICDs), (2) the predictors
      of anxiety, (3) the treatment situation and patients' requests for therapy.
      METHODS: Quantitative and qualitative methods in a prospective design. At
      baseline, 327 ICD outpatients completed validated self-report questionnaires
      (participation rate = 77%). Five months later, a predefined subsample of patients
      (n = 108, participation rate = 81%) consisting of all patients with (n = 58) and
      a randomly selected subsample of patients without (n = 50) elevated symptoms of
      anxiety at baseline, was reassessed using a structured diagnostic interview, the
      baseline questionnaires, and open-ended questions. RESULTS: At baseline, 19.2% of
      patients suffered from at least some form of clinically relevant anxiety with an
      overall remission rate of 56.5% at follow-up. Predictive for anxiety at follow-up
      were higher levels of stress (odds ratio [OR], 1.52, P < 0.001), depression (OR,
      1.26, P < 0.001), somatic symptom severity (OR, 1.25, P < 0.001), more perceived
      ICD-related constraints (OR, 2.4, P = 0.007), lower quality of life (physical
      health: OR, 0.91, P = 0.004; mental health: OR, 0.87, P = 0.001), and a higher
      New York Heart Association class (OR, 7.99, P = 0.002) at baseline. Only 35.3% of
      patients received an evidenced-based treatment for their anxiety disorder. A
      supervised ICD patient group was the most preferred treatment (51.1%).
      CONCLUSIONS: Most patients seemed to adapt well to ICD therapy. Patients
      suffering from additional psychological strains and reporting more negative ICD
      related attitudes were at risk for developing an anxiety disorder. Special
      tailored interventions, such as a supervised ICD patient group, could reduce the
      gap between treatment needs and the treatment situation.

PMID- 24102229
TI  - Mean platelet volume predicts left descending artery occlusion in patients with
      non-ST-elevation myocardial infarction.
AB  - Platelets play an important role in atherothrombosis. As the most common site
      plaque occurs, left anterior descending artery (LAD) infarct location always
      associate with poor prognosis. We sought to assess whether mean platelet volume
      (MPV) could predict LAD infarct location and short-term clinical outcome. In this
      study, 190 consecutive patients with non-ST-elevation myocardial infarction
      (NSTEMI) were enrolled. Clinical, electrocardiography and laboratory
      characteristics were measured. All patients underwent coronary angiography
      examination and had definite culprit vessel during hospitalization. The results
      showed that MPV was smaller in patients with a LAD infarct location than that of
      left circumflex artery or right coronary artery (9.0 +/- 1.5 versus 9.8 +/- 1.6,
      p<0.001). Multivariate analysis also showed that MPV was the only independent
      factor to predict LAD infarct location [Odds ratio (OR)=0.65, 95% confidence
      interval (CI) 0.53-0.80, p<0.0001] in patients with NSTEMI. B-type natriuretic
      peptide and electrocardiography were unreliable predictive factors to locate
      culprit vessel. Receiver operating characteristic curve analysis showed MPV (area
      under the curve: 0.65, 95% CI 0.56-0.74, p<0.01) could reliably discriminate
      those patients with NSTEMI who had a major in-hospital event. Multivariate
      regression analyses also showed that MPV (OR=1.46, 95% CI 1.15-1.86, p<0.01) were
      predictors of major in-hospital events. In conclusion, MPV was the only factor
      independently associated with LAD infarct location in patients with non-ST
      elevation myocardial infarction.

PMID- 24102230
TI  - Editorial Comment to: SAMS: a randomized study comparing two different follow-up
      schedules for active surveillance of low-risk prostate cancer.

PMID- 24102231
TI  - Editorial Comment to: SAMS: a randomized study comparing two different follow-up
      schedules for active surveillance of low-risk prostate cancer.

PMID- 24102233
TI  - One-Pot Fabrication of RGO-Ag3 VO4 Nanocomposites by in situ Photoreduction using
      Different Sacrificial Agents: High Selectivity Toward Catechol Synthesis and
      Photodegradation Ability.
AB  - Weak photon absorption and fast carrier kinetics in graphene restrict its
      applications in photosensitive reactions. Such restrictions/limitations can be
      overcome by covalent coupling of another photosensitive nanostructure to
      graphene, forming graphene-semiconductor nanocomposites. Herein, we report one
      pot synthesis of RGO-Ag3 VO4 nanocomposites using various sacrificial agents like
      ethanol, methanol, propanol and ethylene glycol (EG) under visible light
      illumination. The Raman spectral analysis and (13) C MAS NMR suggest ethanol to
      be the best sacrificial agent among those studied. Thermal analysis studies,
      further, confirm the stability of the synthesized nanocomposite with ethanol as
      sacrificial agent. In view of this, the activity toward dye degradation was
      focused over the composites prepared via ethanol as sacrificial agent. It was
      observed and proved that cationic dyes could be degraded quantitatively and
      swiftly compared to anionic dyes (37.79%) in 1.5 h. This suggests that the
      surface of the nanocomposites is anionic as partial reduction takes place during
      synthesis process. In case of mixed dye degradation process, it was noticed that
      the presence of cationic dye doubles the degradation of anionic dye. The activity
      of these synthesized nanocomposites is more than five-fold toward the
      phototransformation of phenol and photodegradation of textile dyes under visible
      light illumination.

PMID- 24102234
TI  - Plasmonic Enhancement of Dye Sensitized Solar Cells in the Red-to-near-Infrared
      Region using Triangular Core-Shell Ag@SiO2 Nanoparticles.
AB  - Recently, plasmonic metal nanoparticles have been shown to be very effective in
      increasing the light harvesting efficiency (LHE) of dye-sensitized solar cells
      (DSSCs). Most commonly, spherical nanoparticles composed of silver or gold are
      used for this application; however, the localized surface plasmon resonances of
      these isotropic particles have maxima in the 400-550 nm range, limiting any
      plasmonic enhancements to wavelengths below 600 nm. Herein, we demonstrate that
      the incorporation of anisotropic, triangular silver nanoprisms in the photoanode
      of DSSCs can dramatically increase the LHE in the red and near-infrared regions.
      Core-shell Ag@SiO2 nanoprisms were synthesized and incorporated in various
      quantities into the titania pastes used to prepare the photoanodes. This
      optimization led to an overall 32 +/- 17% increase in the power conversion
      efficiency (PCE) of cells made using 0.05% (w/w) of the Ag@SiO2 composite.
      Measurements of the incident photon-to-current efficiency provided further
      evidence that this increase is a result of improved light harvesting in the red
      and near-infrared regions. The effect of shell thickness on nanoparticle
      stability was also investigated, and it was found that thick (30 nm) silica
      shells provide the best protection against corrosion by the triiodide-containing
      electrolyte, while still enabling large improvements in PCE to be realized. 

PMID- 24102235
TI  - Proteomic analysis of cervical vaginal fluid proteins among women in recurrent
      preterm labor.
AB  - OBJECTIVE: Proteomic analysis of four cervical-vaginal fluid (CVF) proteins to
      identify biomarkers of recurrent preterm birth (rPTB) in at-risk women prior to
      onset of preterm labor. METHODS: Nested case control study from 2007 to 2011 of
      women with prior spontaneous preterm birth(s) (PTB) who underwent serial CVF
      sampling. Mass spectrometry analysis was used and ELISA analysis was performed to
      validate candidates. RESULTS: 108 patients were enrolled and 10 cases and 20
      gestational age matched controls were analyzed after exclusions. Of 748 CVF
      proteins identified, 72 had statistically significant (p < 0.05) expression
      differences and 38 were highly differentially expressed (p < 0.01). Four
      candidate proteins were abundant and involved in immune/inflammatory response,
      but ELISA analysis did not confirm altered expression patterns. CONCLUSION: The
      lack of confirmation of potential biomarkers identified by mass spectrometry and
      ELISA demonstrates the challenges of validating PTB biomarkers and suggests that
      a panel of biomarkers would improve the predictive value of CVF testing.

PMID- 24102236
TI  - A new operational paradigm for small-scale ASR in saline aquifers.
AB  - A new operational paradigm is presented for small-scale aquifer storage and
      recovery systems (ASR) in saline aquifers. Regular ASR is often not feasible for
      small-scale storage in saline aquifers because fresh water floats to the top of
      the aquifer where it is unrecoverable. In the new paradigm, fresh water storage
      is combined with salt water extraction from below the fresh water cone. The salt
      water extraction counteracts the buoyancy due to the density difference between
      fresh water and salt water, thus preventing the fresh water from floating up. The
      proposed approach is applied to assess the feasibility of ASR for the seasonal
      storage of fresh water produced by desalination plants in tourist resorts along
      the Egyptian Red Sea coast. In these situations, the continuous extraction of
      salt water can be used for desalination purposes. An analytical Dupuit solution
      is presented for the steady flow of salt water toward a well with a volume of
      fresh water floating on top of the cone of depression. The required salt water
      discharge for the storage of a given volume of fresh water can be computed with
      the analytical solution. Numerical modeling is applied to determine how the
      stored fresh water can be recovered. Three recovery approaches are examined.
      Fresh water recovery rates on the order of 70% are achievable when salt water is
      extracted in high volumes, subsurface impermeable barriers are constructed at a
      distance from the well, or several fresh water recovery drains are used. The
      effect of ambient flow and interruptions of salt water pumping on the recovery
      efficiency are reported. 

PMID- 24102237
TI  - A national database of incidence and treatment outcomes of status epilepticus in
      Thailand.
AB  - Status epilepticus (SE) is a serious neurological condition. The national
      database of SE in Thailand and other developing countries is limited in terms of
      incidence and treatment outcomes. This study was conducted on the prevalence of
      status epilepticus (SE). The study group comprised of adult inpatients (over 18
      years old) with SE throughout Thailand. SE patients were diagnosed and searched
      based on ICD 10 (G41) from the national database. The database used was from
      reimbursement documents submitted by the hospitals under the three health
      insurance systems, namely, the universal health coverage insurance, social
      security, and government health welfare system during the fiscal year 2010. We
      found 2190 SE patients receiving treatment at hospitals (5.10/100 000
      population). The average age was 50.5 years and 1413 patients were males (64.5%).
      Mortality rate was 0.6 death/100 000 population or 11.96% of total patients.
      Significant factors associated with death or a nonimproved status at discharge
      were type of insurance, hospital level, chronic kidney disease, having pneumonia,
      having shock, on mechanical ventilator, and having cardiopulmonary resuscitation.
      In conclusion, the incidence of SE in Thailand was 5.10/100 000 population with
      mortality rate of 0.6/100 000 population.

PMID- 24102238
TI  - Reproducibility of an instrumented measure for passive ankle dorsiflexion in
      conscious and anaesthetized children with cerebral palsy.
AB  - AIM: The aims of this study were to (1) determine whether an instrumented measure
      will reduce measurement error to less than 5 degrees  in children with cerebral
      palsy (CP), (2) determine agreement and reliability of this instrumented measure
      in both conscious and anaesthetized participants, and (3) compare the method with
      previously reported measures. METHOD: Thirty-four ambulant children (15 males, 19
      females), aged 3 to 9 years, with spastic CP were studied in a tertiary-care
      paediatric hospital (21 with hemiplegia, 11 with diplegia, and two with
      quadriplegia). The majority of children functioned at Gross Motor Function
      Classification System level I (n=11) or II (n=18), with five children at level
      III. Ankle dorsiflexion at 50% bodyweight was photographed and measured. Each
      child was measured when conscious and when under mask anaesthesia by two
      experienced assessors. RESULTS: The standard error of measurement (SEM) ranged
      from 3.9 degrees  (anaesthetized; 95% confidence interval [CI] 3.3-4.0 degrees )
      to 6.7 degrees  (conscious; 95% CI 5.3-8.0 degrees ). This compared favourably
      with previously reported dorsiflexion measures (SEM range 6.5-7.8 degrees ) in
      conscious children with CP. Intrarater reliability was good in both conditions
      (intraclass correlation coefficient [ICC]: range 0.95 [anaesthetized; 95% CI 0.92
      0.98] to 0.86 [conscious; 95% CI 0.76-0.95]). The ICC for interrater reliability
      ranged from 0.87 (anaesthetized; 95% CI 0.81-0.93) to 0.65 (conscious; 95% CI
      0.50-0.81). INTERPRETATION: Passive ankle dorsiflexion using an instrumented
      measure has face validity and may assist in the improvement of reproducibility
      under anaesthesia for clinical research. When an individual is conscious, this
      technique is not better than trained assessors using conventional goniometry
      reported in the literature and is not recommended for routine clinical use.

PMID- 24102239
TI  - Text-to-speech technology effects on reading rate and comprehension by adults
      with traumatic brain injury.
AB  - OBJECTIVE: This study's purpose was to examine the comprehension, rate and
      perceptions and reading preferences of adults with severe traumatic brain injury
      (TBI) when reading passages with and without computerized text-to-speech (TTS)
      support. DESIGN AND METHODS: Nine adults with severe TBI read 24 passages in two
      conditions: with and without TTS support. The researchers compared reading rate
      and comprehension accuracy across conditions. Also, participants rated their
      perceived performance and reading preferences via a follow-up questionnaire.
      RESULTS: Comparison to normative data revealed that all nine participants read
      slower than average neurotypical readers. As a group, participants read
      significantly faster with TTS support than without such support, even though the
      TTS reading rate was roughly comparable to the oral rather than silent reading
      rate of neurotypical adults. No significant differences in comprehension resulted
      between the two conditions. Over half of the participants preferred the TTS
      condition over the no-TTS condition. In general, participants were inaccurate in
      judging their relative reading rates and comprehension accuracy across
      conditions. CONCLUSIONS: TTS may improve reading efficiency without compromising
      reading comprehension accuracy for adults with TBI. Given this finding, some
      survivors may find use of TTS technology contributes to increased participation
      in and efficiency when performing reading activities.

PMID- 24102240
TI  - Association of interleukin-6 -174 G>C promoter polymorphism with increased risk
      of type 2 diabetes mellitus patients with diabetic nephropathy in Turkey.
AB  - OBJECTIVE: Diabetic nephropathy (DN) is a serious complication of diabetes
      mellitus. We aimed to evaluate the interleukin (IL)-6 gene polymorphisms in type
      2 DN and control subjects. MATERIALS AND METHODS: The patients selected from the
      Department of Endocrinology and Metabolism Diseases included 43 type 2 diabetes
      mellitus patients without DN and 43 type 2 diabetes mellitus patients with DN and
      340 healthy normal controls. All subjects underwent venous blood drawing for
      complete hormonal assays, lipid profile, glucose, and insulin and Il-6 gene
      polymorphism genetic analysis. RESULTS: IL-6 -174 G>C genotype distribution was
      different between the control group and the type 2 diabetes mellitus patients
      (p=0.004). The higher frequency of the polymorphic G allele was also similar for
      the group with type 2 diabetes mellitus as for the control group. The frequency
      of the polymorphic G allele was 83.9% in diabetic patients with nephropathy
      versus 70.9% in those without nephropathy (p=0.039). CONCLUSION: We suggest that
      the -174 G>C polymorphism of the IL-6 gene is an independent risk factor for DN
      in Turkish type 2 diabetes mellitus patients.

PMID- 24102241
TI  - Multivariate statistical characterization of charged and uncharged domain walls
      in multiferroic hexagonal YMnO3 single crystal visualized by a spherical
      aberration-corrected STEM.
AB  - A state-of-the-art spherical aberration-corrected STEM was fully utilized to
      directly visualize the multiferroic domain structure in a hexagonal YMnO3 single
      crystal at atomic scale. With the aid of multivariate statistical analysis (MSA),
      we obtained unbiased and quantitative maps of ferroelectric domain structures
      with atomic resolution. Such a statistical image analysis of the transition
      region between opposite polarizations has confirmed atomically sharp transitions
      of ferroelectric polarization both in antiparallel (uncharged) and tail-to-tail
      180 degrees  (charged) domain boundaries. Through the analysis, a correlated
      subatomic image shift of Mn-O layers with that of Y layers, exhibiting a double
      arc shape of reversed curvatures, have been elucidated. The amount of image shift
      in Mn-O layers along the c-axis is statistically significant as small as 0.016
      nm, roughly one-third of the evident image shift of 0.048 nm in Y layers.
      Interestingly, a careful analysis has shown that such a subatomic image shift in
      Mn-O layers vanishes at the tail-to-tail 180 degrees  domain boundaries.
      Furthermore, taking advantage of the annular bright field (ABF) imaging technique
      combined with MSA, the tilting of MnO5 bipyramids, the very core mechanism of
      multiferroicity of the material, is evaluated. 

PMID- 24102243
TI  - Direct determination of gibberellic acid in tomato and fruit by using
      photochemically induced fluorescence.
AB  - A simple, sensitive method for determining gibberellic acid based on
      photochemically induced fluorescence detection was developed to determine this
      plant growth regulator in a technical formulation, tomato, and fruit samples. The
      principle for the determination is the photochemical reactivity of the
      gibberellic acid, being consistent with the occurrence of photoaromatization and
      photochemical dimerization with loss of carbon dioxide, and with the likely
      formation of various fluorescent photoproducts. Six min of UV (mainly at 253.7
      nm) irradiation in a solution containing 50% (v/v) methanol and buffer at pH 5
      provided the best results. The calibration curve was linear over the
      concentration range 50-150 ng mL(-1), and the limit of detection was 1.7 ng mL(
      1). The method is useful to determine gibberellic acid in samples with background
      fluorescence such as plum and tomato without the need for labor-intensive
      preparation as a result of UV irradiation suppressing the fluorescent background.

PMID- 24102244
TI  - Biochemical diagnosis of phaeochromocytoma using plasma-free normetanephrine,
      metanephrine and methoxytyramine: importance of supine sampling under fasting
      conditions.
AB  - OBJECTIVE: To document the influences of blood sampling under supine fasting
      versus seated nonfasting conditions on diagnosis of phaeochromocytomas and
      paragangliomas (PPGL) using plasma concentrations of normetanephrine,
      metanephrine and methoxytyramine. DESIGN AND METHODS: Biochemical testing for
      PPGL was performed on 762 patients at six centres, two of which complied with
      requirements for supine sampling after an overnight fast and four of which did
      not. Phaeochromocytomas and paragangliomas were found in 129 patients (67
      noncompliant, 62 compliant) and not in 633 patients (195 noncompliant, 438
      compliant). RESULTS: Plasma concentrations of normetanephrine and methoxytyramine
      did not differ between compliant and noncompliant sampling conditions in patients
      with PPGL but were 49-51% higher in patients without PPGL sampled under
      noncompliant compared with compliant conditions. The 97.5 percentiles of
      distributions were also higher under noncompliant compared with compliant
      conditions for normetanephrine (1.29 vs 0.79 nmol/l), metanephrine (0.49 vs 0.41
      nmol/l) and methoxytyramine (0.42 vs 0.18 nmol/l). Use of upper cut-offs
      established from seated nonfasting sampling conditions resulted in substantially
      decreased diagnostic sensitivity (98% vs 85%). In contrast, use of upper cut-offs
      established from supine fasting conditions resulted in decreased diagnostic
      specificity for testing under noncompliant compared with compliant conditions
      (71% vs 95%). CONCLUSIONS: High diagnostic sensitivity of plasma normetanephrine,
      metanephrine and methoxytyramine for the detection of PPGL can only be guaranteed
      using upper cut-offs of reference intervals established with blood sampling under
      supine fasting conditions. With such cut-offs, sampling under seated nonfasting
      conditions can lead to a 5.7-fold increase in false-positive results
      necessitating repeat sampling under supine fasting conditions.

PMID- 24102242
TI  - Parsing the players: 2-arachidonoylglycerol synthesis and degradation in the CNS.
AB  - The endogenous cannabinoid signalling system, composed of endogenous
      cannabinoids, cannabinoid receptors and the enzymes that synthesize and degrade
      the endogenous cannabinoids, is much more complex than initially conceptualized.
      2-Arachidonoylglycerol (2-AG) is the most abundant endocannabinoid and plays a
      major role in CNS development and synaptic plasticity. Over the past decade, many
      key players in 2-AG synthesis and degradation have been identified and
      characterized. Most 2-AG is synthesized from membrane phospholipids via
      sequential activation of a phospholipase Cbeta and a diacylglycerol lipase,
      although other pathways may contribute in specialized settings. 2-AG breakdown is
      more complicated with at least eight different enzymes participating. These
      enzymes can either degrade 2-AG into its components, arachidonic acid and
      glycerol, or transform 2-AG into highly bioactive signal molecules. The
      implications of the precise temporal and spatial control of the expression and
      function of these pleiotropic metabolizing enzymes have only recently come to be
      appreciated. In this review, we will focus on the primary organization of the
      synthetic and degradative pathways of 2-AG and then discuss more recent findings
      and their implications, with an eye towards the biological and therapeutic
      implications of manipulating 2-AG synthesis and metabolism. LINKED ARTICLES: This
      article is part of a themed section on Cannabinoids 2013. To view the other
      articles in this section visit http://dx.doi.org/10.1111/bph.2014.171.issue-6.

PMID- 24102245
TI  - Isoprene emission protects photosynthesis but reduces plant productivity during
      drought in transgenic tobacco (Nicotiana tabacum) plants.
AB  - Isoprene protects the photosynthetic apparatus of isoprene-emitting plants from
      oxidative stress. The role of isoprene in the response of plants to drought is
      less clear. Water was withheld from transgenic isoprene-emitting and non-emitting
      tobacco (Nicotiana tabacum) plants, to examine: the response of isoprene emission
      to plant water deficit; a possible relationship between concentrations of the
      drought-induced phytohormone abscisic acid (ABA) and isoprene; and whether
      isoprene affected foliar reactive oxygen species (ROS) and lipid peroxidation
      levels. Isoprene emission did not affect whole-plant water use, foliar ABA
      concentration or leaf water potential under water deficit. Compared with well
      watered controls, droughted non-emitting plants significantly increased ROS
      content (31-46%) and lipid peroxidation (30-47%), concomitant with decreased
      operating and maximum efficiencies of photosystem II photochemistry and lower
      leaf and whole-plant water use efficiency (WUE). Droughted isoprene-emitting
      plants showed no increase in ROS content or lipid peroxidation relative to well
      watered controls, despite isoprene emission decreasing before leaf wilting.
      Although isoprene emission protected the photosynthetic apparatus and enhanced
      leaf and whole-plant WUE, non-emitting plants had 8-24% more biomass under
      drought, implying that isoprene emission incurred a yield penalty. 

PMID- 24102246
TI  - Wet work and hand eczema in apprentice nurses; part I of a prospective cohort
      study.
AB  - BACKGROUND /OBJECTIVES: Environmental exposure and personal susceptibility both
      contribute to the development of hand eczema. Here, we report an investigation on
      wet work exposure and its influence on the risk of developing hand eczema in
      apprentice nurses. METHODS: A prospective cohort study was performed among 721
      Dutch apprentice nurses. Participants recorded wet work exposure and symptoms of
      hand eczema using specially designed diary cards. RESULTS: For 533 apprentice
      nurses, a follow-up time of 1-3 years was completed. Diary cards were supplied by
      383 students. The 1-year period prevalence of hand eczema was 23% in the first
      year, 25% in the second year and 31% in the third year of follow-up. Eighty-one
      new cases of hand eczema developed, most of which occurred during the first year
      of follow-up. In approximately one-third of the participants, wet work exposure
      exceeded the national guidelines. Frequent hand washing during traineeships [odds
      ratio (OR) 1.5; 90% confidence interval (CI) 1.0-2.3], frequent hand washing at
      home (OR 2.3; 90% CI 1.5-3.7) and having a side job involving wet work (OR 1.6;
      90% CI 1.0-2.4) were independent risk factors for hand eczema. CONCLUSION: As a
      considerable number of apprentice nurses had already developed hand eczema during
      traineeships, more attention should be paid to skin protection in vocational
      education.

PMID- 24102247
TI  - Stark effect in the benzene dimer.
AB  - Ab initio calculations of the six-dimensional intermolecular potential have shown
      the benzene dimer to be an asymmetric top molecule at equilibrium with one
      benzene moiety forming the "stem" and the other a "tilted cap" in a T-shaped
      structure. Internal rotation of the cap about its C6 axis is essentially free;
      the barriers for cap tilting and for internal rotation of the stem about its C6
      axis are hindered by successively higher barriers. In previous work we have
      validated these theoretical results using Fourier transform microwave
      spectroscopy in conjunction with dynamics calculations. We have also measured the
      Stark effect, and despite the fact that the equilibrium structure is that of an
      asymmetric top, the assigned transitions involving K = 0 exhibit a second-order
      Stark effect whereas those involving K = 1 exhibit a first-order Stark effect.
      This is typical for a symmetric-top molecule, but anomalous for an asymmetric-top
      molecule. We use symmetry arguments to explain how this asymmetric-top molecule
      can have a first-order Stark effect in certain states that have excitation of cap
      internal rotation. Cap internal rotation is essentially the twisting of the
      monomers relative to each other about the intermolecular axis, and such torsional
      motion occurs in other asymmetric top dimers such as benzene-CO and benzene-H2O.
      These latter dimers will also have levels that exhibit a first-order Stark
      effect, which we can explain using our symmetry arguments. 

PMID- 24102248
TI  - Selective retention of methanol over ethanol by a cyclen-based
      cryptand/copper(II) complex.
AB  - A cyclen-based cryptand (2) was prepared in a two-step synthesis from
      dioxocyclen. When a Cu(CF3SO3)2 complex with 2 was prepared in methanol, the
      2/Cu(CF3SO3)2 complex incorporated one methanol in the cavity formed by the
      diethyleneoxy unit and the NH group of the cyclen. When prepared in ethanol, the
      2/Cu(CF3SO3)2 complex similarly incorporated one ethanol. Cold electrospray
      ionization mass spectrometry (CSI-MS) of the 2/Cu(CF3SO3)2/alcohol complexes
      selectively retains methanol over ethanol under CSI-MS conditions. 

PMID- 24102249
TI  - Patient feedback and anaesthetists: what are patients assessing and why?

PMID- 24102250
TI  - Individual-based measurements of light intensity provide new insights into the
      effects of artificial light at night on daily rhythms of urban-dwelling
      songbirds.
AB  - The growing interest in the effects of light pollution on daily and seasonal
      cycles of animals has led to a boost of research in recent years. In birds, it
      has been hypothesized that artificial light at night can affect daily aspects of
      behaviour, but one caveat is the lack of knowledge about the light intensity that
      wild animals, such as birds, are exposed to during the night. Organisms have
      naturally evolved daily rhythms to adapt to the 24-h cycle of day and night,
      thus, it is important to investigate the potential shifts in daily cycles due to
      global anthropogenic processes such as urbanization. We captured adult male
      European blackbirds (Turdus merula) in one rural forest and two urban sites
      differing in the degree of anthropogenic disturbance. We tagged these birds with
      light loggers and simultaneously recorded changes in activity status (active/non
      active) through an automated telemetry system. We first analysed the relationship
      between light at night, weather conditions and date with daily activity onset and
      end. We then compared activity, light at night exposure and noise levels between
      weekdays and weekends. Onset of daily activity was significantly advanced in both
      urban sites compared to the rural population, while end of daily activity did not
      vary either among sites. Birds exposed to higher amounts of light in the late
      night showed earlier onset of activity in the morning, but light at night did not
      influence end of daily activity. Light exposure at night and onset/end of daily
      activity timing was not different between weekdays and weekends, but all noise
      variables were. A strong seasonal effect was detected in both urban and rural
      populations, such as birds tended to be active earlier in the morning and later
      in the evening (relative to civil twilight) in the early breeding season than at
      later stages. Our results point at artificial light at night as a major driver of
      change in timing of daily activity. Future research should focus on the costs and
      benefits of altered daily rhythmicity in birds thriving in urban areas. 

PMID- 24102251
TI  - Increased number of fetal nucleated red blood cells in the placentas of term or
      near-term stillborn and neonates correlates with the presence of diffuse
      intradural hemorrhage in the perinatal period.
AB  - Release of nucleated red blood cells (nRBCs) into the peripheral blood occurs in
      stillbirths/neonates with a probable hypoxic mode of death and antenatal stress.
      We correlated the number of nRBCs in the placenta with the occurrence of
      intradural (IDH) and subdural hemorrhage (SDH) and the potential link with fetal
      hypoxia. Two groups of 22 cases each of nonmacerated term or near-term (>=36
      weeks of gestational age) stillborn or newborns dying in the 1st day of life were
      studied. One group had IDH (with or without SDH) and the other did not have IDH
      or SDH. In each case, the number of nRBCs was determined in 10 consecutive
      placental fields at *40. Data were analyzed with Fisher exact test, receiver
      operating characteristic (ROC) curve analysis, and logistic regression. There was
      a significant association between the diffuse IDH and increased number of nRBCs
      (Fisher exact test P  =  0.0165). An ROC curve analysis showed that the cut-off
      number of nRBCs with the highest accuracy was 2.15 nRBCs/high-power field, with
      79% sensitivity and 67% specificity. The presence of diffuse IDH was associated
      with SDH (Fisher exact test, P  =  0.002). The absence of hypoxic brain change
      was associated with the absence of diffuse IDH (odds ratio 0.308; P  =  0.039).
      We established a significant correlation between the release of nRBCs into the
      placental circulation and the occurrence of diffuse IDH and between diffuse IDH
      and the presence of SDH.

PMID- 24102253
TI  - Substance misuse following Roux-en-Y gastric bypass surgery.
AB  - Post-bariatric surgery patients are overrepresented in substance abuse treatment,
      particularly those who have had the Roux-en-Y gastric bypass (RYGB) procedure.
      The severity of the substance use disorder (SUD; i.e., warranting inpatient
      treatment) and related consequences necessitate a better understanding of the
      variables associated with post-RYGB SUDs. This investigation assessed factors
      associated with post-RYGB substance misuse. Post-RYGB patients (N = 141; at least
      24 months postsurgery) completed an online survey assessing variables
      hypothesized to contribute to post-RYGB SUDs. Fourteen percent of participants
      met criteria for postoperative substance misuse. Those with a lower percent total
      weight loss (%TWL) were more likely to endorse substance misuse. Family history
      of substance misuse was strongly associated with postoperative substance misuse.
      Eating-related variables including presurgical food addiction and postsurgical
      nocturnal eating, subjective hunger, and environmental responsiveness to food
      cues were also associated with a probable postoperative SUD. These findings have
      clinical utility in that family history of substance misuse can be easily
      assessed, and at-risk patients can be advised accordingly. In addition, those who
      endorse post-RYGB substance misuse appear to have stronger cognitive and
      behavioral responses to food, providing some support for the theory of behavioral
      substitution (or "addiction transfer"). 

PMID- 24102252
TI  - Using domestic well records to determine fractured bedrock watersheds and
      recharge rates.
AB  - This study presents an approach for delineating groundwater basins and estimating
      rates of recharge to fractured crystalline bedrock. It entailed the use of
      completion report data (boring logs) from 2500 domestic wells in bedrock from the
      Coventry Quadrangle, which is located in northeastern Connecticut and
      characterized by metamorphic gneiss and schist. Completion report data were
      digitized and imported into ArcGIS((r)) for data analysis. The data were
      processed to delineate groundwater drainage basins for the fractured rock based
      on flow conditions and to estimate groundwater recharge to the bedrock. Results
      indicate that drainage basins derived from surface topography, in general, may
      not correspond with bedrock drainage basins due to scale. Estimates of recharge
      to the bedrock for the study area indicate that only a small fraction of the
      precipitation or the amount of water that enters the overburden recharges the
      rock. The approach presented here can be a useful method for water resource
      related assessments that involve fractured rock aquifers. 

PMID- 24102254
TI  - Is low BMI associated with specific drug use among injecting drug users?
AB  - Body mass index (BMI) of a sample of people who regularly inject drugs (N = 781)
      was examined to gauge the impact of specific types of drug use. Cross-sectional
      interviews were undertaken in 2010 as part of a national monitoring program
      funded by the Australian Government. Latent class analysis identified three
      groups of drug users, with heroin users at 3.4 times the risk of being
      underweight compared with amphetamine users, and amphetamine users were at almost
      twice the odds of being obese compared with lower level morphine users. Nutrition
      should play a part in harm minimization. 

PMID- 24102255
TI  - Branch-like hierarchical heterostructure (alpha-Fe2O3/TiO2): a novel sensing
      material for trimethylamine gas sensor.
AB  - A novel hierarchical heterostructure of alpha-Fe2O3 nanorods/TiO2 nanofibers with
      branch-like nanostructures was fabricated using a simple two-step process called
      the electrospinning technique and hydrothermal process. A high density of alpha
      Fe2O3 nanorods (about 200 nm in diameter) was uniformly deposited on a TiO2
      nanofibers backbone. The phase purity, morphology, and structure of hierarchical
      heterostructures are investigated by X-ray diffraction (XRD), field emission
      scanning electron microscopy (FESEM), transmission electron microscopy (TEM), and
      energy-dispersive X-ray (EDX) analysis. The highly branched alpha-Fe2O3/TiO2
      heterostructures provided an extremely porous matrix and high specific surface
      area required for high-performance gas sensors. Different nanostructured alpha
      Fe2O3/TiO2 heterostructures are also investigated by controlling the volume ratio
      of the reactants. The alpha-Fe2O3/TiO2 heterostructures with a proper mixture
      ratio of the reactants sensor exhibit obviously enhanced sensing characteristics,
      including higher sensing response, lower operating temperature, faster response
      speed, and better selectivity in comparison with other ones. Moreover, the alpha
      Fe2O3/TiO2 heterostructures sensor also exhibits excellent sensing performances
      compared with alpha-Fe2O3 nanorods and TiO2 nanofibers sensors. Thus, the
      combination of TiO2 nanofibers backbone and alpha-Fe2O3 nanorods uniformly
      decorated endows a fascinating sensing performance as a novel sensing material
      with high response and rapid responding and recovering speed. 

PMID- 24102256
TI  - Risk factors and trends in the rate of stillbirth in Hungary between 1971 and
      2010.
AB  - OBJECTIVE: Possible risk factors and trends in the rate of stillbirth in Hungary
      between 1971 and 2010. METHODS: Annual data of fetal birth weight, fetal gender,
      maternal age and marital status of the mother categories were available for both
      live and stillborn cases and were analyzed using negative binomial regression. A
      p value less than 0.05 was considered significant. RESULTS: Male gender
      significantly increased risk of stillbirth (relative risk (RR):1.08; p < 0.001).
      The risk of stillbirth was also significantly associated with the maternal age
      (RR: 2.01 in the group older than 35 years, relative to younger mothers; p <
      0.001), and the marital status (RR: 1.24 among the babies of an extramarital
      partnership; p < 0.001), this holding true for both fetal genders. However, a low
      birth weight ( < 2500 g) increased the risk of stillbirth more than 18-fold (RR:
      18.47; p < 0.001) and there was a markedly higher risk of low birth weight in
      boys than in girls. Further, a strong negative correlation (r = -0.88) was
      detected between the real income per person of the overall population and the
      rate of stillbirth. CONCLUSIONS: These findings support the known risk factors of
      stillbirth and gender-specific analyses given an estimation of the risk of
      stillbirth in both boys and girls.

PMID- 24102257
TI  - A simple and straightforward approach to quinoxalines by iron/sulfur-catalyzed
      redox condensation of o-nitroanilines and phenethylamines.
AB  - In situ generated iron sulfide from elemental sulfur and ferric chloride was
      found to be a highly efficient catalyst for the redox condensation cascade
      reaction between o-nitroanilines and 2-arylethylamines. This method constitutes a
      new atom-, step-, and redox-economical route to 2-arylquinoxalines. 

PMID- 24102258
TI  - Thermal stability of DNA functionalized gold nanoparticles.
AB  - Therapeutic uses of DNA functionalized gold nanoparticles (DNA-AuNPs) have shown
      great potential and exciting opportunities for disease diagnostics and treatment.
      Maintaining stable conjugation between DNA oligonucleotides and gold
      nanoparticles under thermally stressed conditions is one of the critical aspects
      for any of the practical applications. We systematically studied the thermal
      stability of DNA-AuNPs as affected by organosulfur anchor groups and packing
      densities. Using a fluorescence assay to determine the kinetics of releasing DNA
      molecules from DNA-AuNPs, we observed an opposite trend between the temperature
      induced and chemical-induced release of DNA from DNA-AuNPs when comparing the DNA
      AuNPs that were constructed with different anchor groups. Specifically, the
      bidentate Au-S bond formed with cyclic disulfide was thermally less stable than
      those formed with thiol or acyclic disulfide. However, the same bidentate Au-S
      bond was chemically more stable under the treatment of competing thiols
      (mercaptohexanol or dithiothreitol). DNA packing density on AuNPs influenced the
      thermal stability of DNA-AuNPs at 37  degrees C, but this effect was minimum as
      temperature increased to 85  degrees C. With the improved understanding from
      these results, we were able to design a strategy to enhance the stability of DNA
      AuNPs by conjugating double-stranded DNA to AuNPs through multiple thiol anchors.

PMID- 24102260
TI  - Growth inhibition and antioxidative response of wood decay fungi exposed to plant
      extracts of Casearia species.
AB  - Ligninolytic fungi take part in critical processes in ecosystems such as nutrient
      recycling; however, some fungal species can be pathogenic to forest and urban
      trees and deteriorate wood products. The tropical flora is an important source of
      antimicrobial compounds environmentally safer than traditional wood
      preservatives. Therefore, this study aimed to evaluate the inhibitory activity of
      ethanol plant extracts of Casearia sylvestris and Casearia decandra on the white
      rot wood decay basidiomycetes Trametes villosa and Pycnoporus sanguineus. In
      addition, the effect of the extracts on the fungal antioxidative metabolism was
      studied. Among the different substances present in the extracts, the
      phytochemical analyses identified a clerodane diterpenoid (C. sylvestris) and
      cinnamic acid, hydroquinone and beta-sitosterol (C. decandra). The extracts
      inhibited the fungi up to 70% and caused hyphal morphology changes. The extracts
      triggered oxidative stress process as indicated by the increased levels of the
      antioxidant enzymes catalase and glutathione reductase. Therefore, the Casearia
      extracts are a potential source of natural biocides to control wood decay fungi,
      and one of the mechanisms of action is the oxidative stress. SIGNIFICANCE AND
      IMPACT OF THE STUDY: The Casearia plant extracts exhibited important antifungal
      activity on wood decay fungi and triggered oxidative stress process, an
      inhibitory mechanism rarely studied in filamentous fungi exposed to plant
      extracts. Therefore, a starting point was provided for the development of natural
      compounds-based products as an alternative to chemical fungicides. In addition,
      subsidies were given to further studies in order to elucidate in more detail how
      compounds present in extracts of native tropical plants affect the physiology of
      fungi.

PMID- 24102261
TI  - Child disability services in Bangladesh: Scherzer et al. reply.

PMID- 24102259
TI  - The role of midkine in skeletal remodelling.
AB  - Bone tissue is subjected to continuous remodelling, replacing old or damaged bone
      throughout life. In bone remodelling, the coordinated activities of bone-forming
      osteoblasts and bone-resorbing osteoclasts ensure the maintenance of bone mass
      and strength. In early life, the balance of these cellular activities is tightly
      regulated by various factors, including systemic hormones, the mechanical
      environment and locally released growth factors. Age-related changes in the
      activity of these factors in bone remodelling can result in diseases with low
      bone mass, such as osteoporosis. Osteoporosis is a systemic and age-related
      skeletal disease characterized by low bone mass and structural degeneration of
      bone tissue, predisposing the patient to an increased fracture risk. The growth
      factor midkine (Mdk) plays a key role in bone remodelling and it is expressed
      during bone formation and fracture repair. Using a mouse deficient in Mdk, our
      group have identified this protein as a negative regulator of bone formation and
      mechanically induced bone remodelling. Thus, specific Mdk antagonists might
      represent a therapeutic option for diseases characterized by low bone mass, such
      as osteoporosis. LINKED ARTICLES: This article is part of a themed section on
      Midkine. To view the other articles in this section visit
      http://dx.doi.org/10.1111/bph.2014.171.issue-4.

PMID- 24102262
TI  - Substantial under-treatment among women diagnosed with osteoporosis in a US
      managed-care population: a retrospective analysis.
AB  - BACKGROUND: Multiple therapies are approved for the treatment of osteoporosis
      (OP), but many patients with osteoporosis may not initiate treatment upon
      osteoporosis diagnosis. OBJECTIVE: To characterize initiation of pharmacologic OP
      treatment among women within 1 year of OP diagnosis in a US managed care
      population. RESEARCH DESIGN AND METHODS: The retrospective cohort study included
      women aged >=55 years with a claims-documented diagnosis of OP who were naive to
      OP medications prior to OP diagnosis (index date) during 2001-2010. Continuous
      enrollment for 12 months before (baseline) and after (follow-up) the index date
      was required. Patients who received OP medications but did not have an OP
      diagnosis were excluded. Differences in baseline characteristics between the
      treated and untreated cohorts were compared using Wilcoxon rank-sum (continuous
      variables) and chi-square tests (categorical variables). MAIN OUTCOMES MEASURES:
      During the follow-up period, the percentages of patients treated with
      bisphosphonates (alendronate, ibandronate, risedronate, zoledronic acid) and non
      bisphosphonates (calcitonin, raloxifene, teriparatide) were determined. RESULTS:
      A total of 65,344 patients, mean age 65.7 years, met study inclusion exclusion
      criteria. During the follow-up period, 42,033 patients (64.3%) received no OP
      medication and 23,311 patients (35.7%) received OP treatment. A total of 20,200
      patients (30.9% of total study population) received bisphosphonates and 3111
      (4.8% of total) patients received non-bisphosphonates as their index medication.
      At baseline, untreated patients were slightly older and had higher rates of
      hypertension, chronic inflammatory joint disease, diabetes mellitus, and
      gastrointestinal events (p <= 0.01) compared with treated patients. CONCLUSIONS:
      Among women aged >=55 years in a US managed-care population, 64.3% received no
      pharmacologic treatment within 1 year after being diagnosed with OP. The authors
      were not able to determine if untreated patients did not receive or did not fill
      a prescription. Further research is needed to understand the barriers to OP
      treatment and reasons for non-treatment.

PMID- 24102263
TI  - Prevalence of cardiac sarcoidosis in patients presenting with monomorphic
      ventricular tachycardia.
AB  - INTRODUCTION: Sarcoidosis is a granulomatous disease of unknown etiology, which
      involves the heart in 5-25% of cases. Although ventricular tachycardia (VT) has
      been reported as the first presentation of sarcoidosis, its prevalence has not
      previously been investigated. In this prospective study, we sought to
      systematically investigate the prevalence of cardiac sarcoidosis (CS) in patients
      presenting with monomorphic VT (MMVT) and no previous history of sarcoidosis.
      METHODS: Consecutive patients presenting with MMVT to a tertiary care center were
      screened for inclusion. Patients with idiopathic VT, VT secondary to coronary
      artery disease, or prior diagnosis of sarcoidosis were excluded. Included
      patients underwent F-18-fluorodeoxyglucose positron emission tomography (PET)
      scan. In subjects with PET scanning suggestive of active myocardial inflammation,
      histological diagnosis was confirmed through extracardiac or endomyocardial
      biopsy (EMB). RESULTS: A total of 182 patients presented to our institution with
      VT between February 2010 and September 2012 and 14 subjects met inclusion
      criteria. Within this group, six of 14 (42%) patients had abnormal PET scans
      suggesting active myocardial inflammation. Four of the six patients had tissue
      biopsies that were diagnostic of sarcoidosis; the remaining two patients had
      guided EMB indicating nonspecific myocarditis. Atrioventricular block was
      observed in three of four (75%) patients with CS and none in 10 of the others (P
      = 0.022). Three of the four patients had pulmonary sarcoidosis and one patient
      had isolated CS. All four patients were treated with corticosteroids. CONCLUSION:
      In this prospective study, four of 14 (28%) patients presenting with MMVT
      (without idiopathic VT, ischemic VT, or known sarcoidosis) had CS as the
      underlying etiology. Clinicians should consider screening for CS in patients with
      unexplained MMVT.

PMID- 24102264
TI  - Activated platelet chemiluminescence and presence of CD45+ platelets in patients
      with acute myocardial infarction.
AB  - It has been found that in 15% of acute myocardial infarction patients' platelets
      generate reactive oxygen species that can be detected with luminol-enhanced
      chemiluminescence of platelet-rich plasma within 8-10 days after acute myocardial
      infarction. This increase in generate reactive oxygen species production
      coincides with the emergence of CD45(+) platelets. The ability of platelets to
      carry surface leukocyte antigen implies their participation in exchange of
      specific proteins in the course of acute myocardial infarction. Future studies of
      CD45(+) platelets in peripheral blood of acute myocardial infarction patients in
      association with generate reactive oxygen species production may provide a new
      insight into the complex mechanisms of cell-cell interactions associated with
      acute myocardial infarction.

PMID- 24102265
TI  - Evolution of the cognitive profile in school-aged patients with severe TBI during
      the first 2 years of neurorehabilitation.
AB  - OBJECTIVE: Persistent post-injury cognitive, academic and behavioural deficits
      have been documented in children who sustained severe TBI during the school-age
      years. The major aim of this study was to examine and follow-up for 2 years the
      cognitive profile of a sample of post-injured patients (aged 6-16.11), in order
      to verify to what extent they recovered their intellectual functions after
      rehabilitation. METHOD: Twenty-six patients who received a specific
      neuropsychological treatment and three cognitive evaluations with WISC-III were
      selected from a pool of 77. RESULTS: This group of patients showed a mild
      cognitive deficit at baseline, which improved over the 2 years to a borderline
      level. Despite the improvement in intellectual quotients and single sub-test
      scores achieved through rehabilitation, different recovery times were seen
      according to the function under study. The most common deficits are in processing
      speed, inferential and lexical-semantic skills. CONCLUSIONS: Detailed analysis of
      the WISC-III sub-tests allows for an accurate description of single cognitive
      functions after TBI. This allows one to make differential diagnoses between
      functional profiles and plan individualized rehabilitation treatments. Post
      injured school-aged patients should receive rehabilitation for a period of at
      least 2 years, which is the time necessary for an at-least partial reorganization
      of basic cognitive functions.

PMID- 24102266
TI  - Facilitation as a ubiquitous driver of biodiversity.
AB  - Models describing the biotic drivers that create and maintain biological
      diversity within trophic levels have focused primarily on negative interactions
      (i.e. competition), leaving marginal room for positive interactions (i.e.
      facilitation). We show facilitation to be a ubiquitous driver of biodiversity by
      first noting that all species use resources and thus change the local biotic or
      abiotic conditions, altering the available multidimensional niches. This can
      cause a shift in local species composition, which can cause an increase in beta,
      and sometimes alpha, diversity. We show that these increases are ubiquitous
      across ecosystems. These positive effects on diversity occur via a broad host of
      disparate direct and indirect mechanisms. We identify and unify several of these
      facilitative mechanisms and discuss why it has been easy to underappreciate the
      importance of facilitation. We show that net positive effects have a long history
      of being considered ecologically or evolutionarily unstable, and we present
      recent evidence of its potential stability. Facilitation goes well beyond the
      common case of stress amelioration and it probably gains importance as community
      complexity increases. While biodiversity is, in part, created by species
      exploiting many niches, many niches are available to exploit only because species
      create them.

PMID- 24102268
TI  - Reply to: 'vitamin D deficiency during pregnancy: confronting the issues'.

PMID- 24102267
TI  - Family background of Diabetes Mellitus, obesity and hypertension affects the
      phenotype and first symptom of patients with PCOS.
AB  - BACKGROUND: The phenotypic variability among PCOS could be due to differences in
      insulin patterns. Hyperinsulinemia commonly accompanies Diabetes Mellitus (DM),
      obesity, hypertension and CAD, though, to a variable degree. We speculate that a
      family history of these diseases could differentially affect the phenotype of
      PCOS. AIM: To study the effect of DM/CAD/HT and obesity on the phenotype of PCOS.
      METHODS: PCOS patients and age matched controls were enquired for a family
      background of DM, hypertension, CAD and obesity among parents and grandparents.
      Regression modelling was employed to examine predictors of obesity and first
      symptom in PCOS patients. RESULTS: There were 88 PCOS women and 77 age-matched
      controls (46 lean, 31 obese). A high prevalence of DM, CAD, obesity and
      hypertension was observed among parents and grandparents of women with PCOS
      compared to controls. Hypertension and CAD manifested more in father's side of
      family. BMI of PCOS subjects was significantly related to parental DM and obesity
      after correcting for age. First symptom of weight gain was significantly
      associated with number of parents with DM (p = 0.02) and first symptom of
      irregular periods was associated with number of parents with hypertension (p =
      0.06). CONCLUSION: A family background of DM/HT and obesity diseases affects the
      phenotype of PCOS.

PMID- 24102269
TI  - Discovery of P3971 an orally efficacious novel anticancer agent targeting HIF
      1alpha and STAT3 pathways.
AB  - Hypoxia-inducible factor-1alpha (HIF-1alpha) and signal transducer and activator
      of transcription 3 (STAT3) are transcription factors and are activated in
      response to hypoxia. Both HIF-1alpha and STAT3 regulate various aspects of cancer
      biology such as cell survival, proliferation, angiogenesis etc. and are
      constitutively expressed in a wide range of human cancers. In the last decade,
      over expression of HIF-1alpha and STAT3 has been demonstrated in many common
      human cancers, thereby emerging as highly compelling anticancer targets for drug
      discovery. We herein report the design and synthesis of new imidazopyridine based
      potent dual inhibitors of HIF-1alpha and STAT3 pathways. The lead compound of
      this series P3971 has been identified as a potent inhibitor of HIF-1alpha (200
      nM) and STAT3 (350 nM) with significant antiproliferative activity against
      various cancer cell lines. Moreover, P3971 was also found to be orally
      efficacious in HCT116 (colon cancer) and H460 (lung cancer) xenograft mice
      models. 

PMID- 24102270
TI  - Management of elderly patients with diffuse large B-cell lymphomas.
AB  - Life expectancy has impressively increased over the past century and the US
      population over 65 years is rapidly growing, especially those over 80 years. In
      fact, persons older than 80 years have increased by more than 250% between the
      years 1960 and 2000, and it is expected that the population aged >75 years will
      triple by the year 2030. With the increase of the geriatric population, there is
      a need for the development and validation of treatment strategies for NHL for
      these patients. Therapy in elderly patients needs special attention because older
      patients usually suffered of several co-morbidities and their management
      represents a challenge for physicians. In fact, older patients treated for
      lymphoma may not tolerate the high-dose therapies used in younger patients and
      have increased risk of therapy-related toxicity as a result of age-related
      physiological changes and frequent co-morbidities. The widespread use of a
      comprehensive geriatric assessment tool might overcome the difficulty to run
      prospective clinical trial in elderly patients with lymphoma. 

PMID- 24102271
TI  - Autologus stem cell transplatation as a care option in elderly patients. A
      review.
AB  - The ageing population and the increase in life expectancy have put new social and
      health questions into the public health agenda of western countries.
      Hematological cancer incidence peaks in older population as a logical consequence
      of a longer lifespan promoting prolonged exposure to carcinogens and accumulation
      of genetic alterations. Hematological cancer represents a major cause of
      mortality in this age group despite recent progress observed in the management of
      cancer in the general population. Autologous stem cell transplantation (ASCT)
      represents a therapeutic option in the treatment of a large proportion of
      lymphomas and multiple myeloma, but their role in the onco-geriatric setting
      remains an open question, due to the presence of chronic disease. Ageing is
      characterized by progressive decrements in physiologic reserves and abilities to
      compensate for physical and/or functional limitations, which increase the risk of
      developing morbidity and disability. These events explains the extreme diversity
      of ageing individuals in terms of clinical and functional status. As a
      consequence, life expectancy in the elderly is influenced not only by the
      neoplastic diseases itself but also by the various co-morbidities common to this
      age group. The management of elderly people with hematological diseases
      potentially curative, should therefore combine both geriatric and tumor
      assessments. Among the elderly patients identified as being candidates for AHSCT,
      after the mobilization of progenitor cells from the bone marrow into the
      peripheral blood, the aphaeresis procedure is the most common method for
      collecting an adequate number of stem cells. The proper selection of patients may
      greatly improve the results and the toxicity related to cancer treatment in the
      elderly. We recommend the adoption of some form of geriatric assessment in the
      evaluation of any patient who is 70 years and older, this review intends to offer
      an overview of the state of art in ASCT in elderly patients. 

PMID- 24102272
TI  - Gastrointestinal non colorectal cancer. Do elderly patients need a specific
      management?
AB  - BACKGROUND: Elderly patients (65 years and over) develop often, sometimes
      predominantly , esophageal, gastro esophageal junction, gastric and pancreatic
      cancer (gastrointestinal non colorectal cancer). Most clinical trials exclude
      elderly patients from accrual considering aging a potential risk factor. In fact
      an elderly patient can develop greater toxicity than a younger patient from
      oncologic treatments (chemotherapy, radiotherapy, target therapies) due to a
      worse function of vital organs. METHODS: We analyzed the current scientific
      literature, searching articles since 1990, about gastrointestinal non colorectal
      cancer in elderly patients, to establish if they need a specific management,
      different from younger patients. RESULTS: Data from analyzed studies, both gastro
      esophageal and pancreatic cancer, are contradictory. In some reports elderly
      patients don't seem to bring greater toxicity than younger. Other trials consider
      that dose-adjustment to renal function is need in elderly patients, but these
      trials are very few. Other trials may include several biases such as accrual of
      "only fit" elderly patients. CONCLUSIONS: It is very important in elderly
      patients with higher risk of toxicity, to distinguish the aim of cancer
      treatment: is it curative or palliative? Furthermore, in this type of patients
      the most important target is probably maintaining the quality of life especially
      in gastric and pancreatic cancer that often started as advanced disease. For
      these valuation chronological age alone is not sufficient. Another very important
      factor in elderly cancer patients is the geriatric assessment including not only
      age but also functional, social and mental status.

PMID- 24102274
TI  - Treatment of elderly patients affected by lung cancer: why to treat, when to
      treat and what we know.
AB  - In the recent years many advances have been achieved in the field of the
      treatment of lung cancer; with the development of novel therapeutic pathways due
      to the knowledge of oncologic drivers involved in the carcinogenesis of the lung,
      as well as the involvement of new radiotherapic and surgical techniques.
      Nevertheless, the standard treatment for elderly is still debated, mainly because
      of an underrepresentation of elderly patients in clinical trials. Herein we try
      to summarize the main guidelines for the treatment of lung cancer, with
      particular attention for the elderly patients, what we know and what has changed.

PMID- 24102275
TI  - Hematopoietic Growth Factor support in the Elderly treated with Chemotherapy.
AB  - The 60% of tumors affected patients >65years of age and the future previsions are
      considering an amount of 70% after 2030. Elderly Patients presents multiple
      comorbidity, polipharmacy, and disability. Geriatric assessment helps physicians
      to take the best therapeutic decisions. Clinical conditions influence efficacy
      and tolerability of chemotherapy. Prophylactic use of G-CSF after chemotherapy
      lowers the rate and length of severe neutropenia , and decreases the episodes of
      febrile neutropenia. Anemia is a hematologic condition associated with ageing ,
      but is frequently associated to concomitant chronic disease. Stem cells display
      increasing resistance to erythropoietin in the elderly patients and this is
      connected with the onset of pro-inflammatory cytokines characteristic of this age
      . Anemia is a common adverse event in cancer patients receiving chemotherapy.
      Several of the symptoms associated with anemia, such as fatigue, syncope,
      palpitations and dyspnea, reduce patient activity and have a profound effect on
      the quality of life [QOL]. Considering the unfit or frail status of elderly
      patient the at home use of pegfilgrastim and weekly or three weekly
      erythropoietin administration could be preferred for this setting of patients
      that lack of specialized nursing care or facilities. Further studies, considering
      the several differences in health organizations in vary countries, could be held
      to state the real impact of the biosimilars in comparison to the long acting
      originators in the reduction of costs in this group of patients.

PMID- 24102273
TI  - Is effective and safe a radiochemotherapy approach in elderly cancer patients? A
      review.
AB  - Although more than 60% of all cancer patients in Europe and the USA are older
      than 65 years at the time of diagnosis, elderly patients are generally under
      represented in clinical trials. A general consensus on how to treat elderly
      patients is still far from being achieved. In this review, we address some of the
      issues and challenges surrounding the treatment of older cancer patients and
      radiochemotherapy. We discuss the existing evidence related to radiochemotherapy
      in the elderly, focusing primarily on the malignancies most commonly seen in
      older patients and making general treatment recommendations where applicable. 

PMID- 24102276
TI  - Genito-urological cancers in elderly patients.
AB  - Age is now widely accepted as the greatest single risk factor for developing
      cancer, and cancer is considered primarily as a disease of the elderly.
      Furthermore, a characteristic of aging is the progressive deterioration of immune
      function known as immunosenescence. In addition to the increased risk of
      occurrence of cancer among older patients, they are more predisposed to poor
      outcomes after definitive treatment. Therapies, outcomes and mortality are often
      influenced by age and elderly must have a specific and a multidisciplinary
      approach. It is obvious to consider that one should not consider "age" as the
      only risk factor, but the condition that this determines to the organism, like
      the presence of co-morbidities and the consequent poor response to treatment.
      Cancer occurs frequently in association of one or more other chronic diseases,
      that affect the efficacy of various treatment interventions. Because of the
      potential morbidity associated with surgery, the use of mini-invasive techniques
      have expanded considerably. Aging should not be viewed as a difficulty to
      definitive therapeutic option. For these reason, it should be correct to value
      the physiologic capabilities of each organ system and all co-morbidities in the
      elderly, in order to face possible risks of treatment or improbable benefits.
      This review takes a look to the tumor biology and to the morbidity of cancer
      treatment in elderly patients affected by genito-urological cancer like prostate,
      bladder and renal cancer. 

PMID- 24102277
TI  - Colorectal cancer in elderly patients: from best supportive care to cure.
AB  - Colorectal cancer is one of the major causes of cancer mortality in the elderly
      population (median age at diagnosis of 71 years) in Western Countries. Moreover
      patients with metastatic disease are often elderly with significant co-
      morbidities. Unfortunately, elderly patients are often untreated and under
      represented in clinical trials, even if most clinical trials that have included
      this setting of population have shown similar survival rates and toxicities to
      younger patients. Age itself should not be considered for candidacy to
      chemotherapy but it should be taken in consideration the great heterogeneity of
      co-morbidities present in the elderly population. Therefore, the best treatment
      strategy for elderly colorectal cancer patients has not yet been defined.
      Comprehensive Geriatric Assessment is recommended to evaluate the best strategy
      treatment and to reduce the adverse events. In fact, while fit elderly patients
      could receive the same therapeutic treatment as the younger counterpart, a
      palliative approach should be taken in consideration for frail elderly patients
      and for those with a short life expectancy. 

PMID- 24102278
TI  - Skin cancers in elderly patients.
AB  - Cancer in older people is a common problem worldwide. Among various types of
      cancer, skin cancers represent an important percentage. The principal risk
      factors are sun exposure, family history of skin cancer, fair skin color, but
      also the age plays an important role in the genesis of skin cancers. In older
      people there are a more prolonged exposure to carcinogenesis and a decreased
      functionality of reparation mechanisms of the cells so they acquire a selective
      advantage of growing and proliferating. At the same time age causes alteration in
      immune system by increasing NK-cells absolute number and decreasing both the
      endogenous and the lymphokine-induced lytic activities. The anti-tumor immune
      response is also mediated by the cytotoxic T- lymphocytes and in the elderly a
      strong reduction of T-cell function has been demonstrated. In elderly patients
      the diagnosis and the treatment of skin cancers can be different from younger
      counterpart. For example in older patients with melanoma is important to evaluate
      Breslow depth while higher mitotic rate has major value in younger patients.
      Moreover, the treatment should consider the performance status of patients and
      their compliance. 

PMID- 24102279
TI  - Cancer, aging and immune reconstitution.
AB  - Aging is a complex phenomenon involving multiple physiological functions. Among
      these, very important are the modifications induced in the immune system; these
      modifications may be related to cancer development, a disease of older people. We
      herein describe the age-dependent alterations observed in the various arms of the
      immune system. Both innate and adaptive immunity are compromised during aging, a
      condition where an inflammatory status contributes to promote immune suppression
      and tumour growth. Collectively, aging of the immune system may produce
      detrimental consequences on the response against tumours in old patients. In
      fact, preclinical studies and clinical observations in humans have demonstrated
      age-associated alterations in antitumor immunity. Immunological recovery of old
      patients after conventional chemotherapy (CT) has not been fully investigated,
      while several studies conducted in patients undergoing blood stem cell
      transplantation have demonstrated that a delayed immune reconstitution associated
      with older age results in increased susceptibility to opportunistic infections
      and risk of tumour relapse. Cellular immunotherapy and vaccination are becoming
      viable options for improving survival and quality of life of cancer patients
      targeting both the host defences and the tumour. The clinical experience in
      elderly patients is still in its infancy, but available data indicate that these
      approaches are feasible and promising. A key problem in the studies on aging,
      immunity and cancer is that it is difficult to distinguish changes related to age
      from those related to cancer-dependent immunosuppression, but independent from
      the age of the subject. Longitudinal studies on aged healthy and cancer persons
      and the use of new immunological techniques may be required to clarify these
      issues. 

PMID- 24102280
TI  - Oxaliplapin and capecitabine (XELOX) based chemotherapy in the treatment of
      metastatic colorectal cancer: the right choice in elderly patients.
AB  - PURPOSE: Elderly patients with metastatic colorectal cancer (mCRC) differ from
      the general population and are underrepresented in clinical trials. We,
      retrospectively, analyzed the safety and efficacy of XELOX regimen in the
      treatment of elderly patients affected by mCRC. PATIENTS AND METHODS: One-hundred
      eleven consecutive patients, aged 70 years or older, were enrolled in the study.
      RESULTS: All patients were evaluated for safety and efficacy (male/female,
      63/48). Median age was 75 years (range 71-85 years). Median Eastern Cooperative
      Oncology Group Performance Status (ECOG PS) was 0 (range 0-2). Metastatic sites
      distribution is as follows: liver (44.1%), lung (13.5%), liver plus lung (12.6%)
      and other (29.7%). A total of 584 cycles were administered (median 6
      cycles/patient, range 2-10). Median follow-up time was 14.5 months (range 1-41
      months). In an intent-to-treat analysis, objective responses and stable disease
      were recorded in 41 (40.4%) and 29 (26.6%) patients, respectively. The median
      response duration was 5.9 months (range 0.5-28.8). The median progression free
      survival (PFS) was 7.5 months (range 1-26 months). The median overall survival
      (OS) was 15 months (range 1-64 months). The grade 3 toxicities were: neutropenia
      (8.1%), diarrhea and neurotoxicity (5.4% respectively). Most adverse events were
      mild to moderate; the most common was acute sensory neuropathy (57.6%).
      CONCLUSION: XELOX is a highly effective first-line treatment for mCRC elderly
      patients. Response rates, PFS and OS are similar to those observed with
      fluorouracil/leucovorin/oxaliplatin combinations. XELOX is a convenient regimen,
      likely to be preferred by both patient and healthcare providers.

PMID- 24102281
TI  - The complexity of aging: cancer risk among elderly people and infectious risk
      among those with cancer.
AB  - Aging is associated with a reduced capability of the immune system to adequately
      respond to pathogens and to prevent tumor formation. As a consequence of
      immunosenescence, older people have a higher risk to develop infections as well
      as cancer. In addition, cancer itself may expose old patients to infections,
      including opportunistic infections, i.e. Pseudomonas aeruginosa, Aspergillus
      fumigatus and Cytomegalovirus infection. Patients with hematologic malignancies
      have a higher risk than patients with solid tumors, because of more prolonged
      disease-related and treatment-related neutropenia and intensive immunosuppressive
      regimens. Co-existing medical conditions, e.g. chronic renal failure, diabetes
      mellitus, emphysema, which are quite common in the elderly, may also contribute
      to rising the infectious risk, as well as the use of long term vascular
      catheters, which is required in a large number of cancer patients to administrate
      chemotherapy. Neutropenic infections do not only represent a major cause of
      morbidity and mortality, but may be responsible for a reduction of the
      antineoplastic treatment dose and dose intensity, thus compromising the overall
      treatment effectiveness. The use of antibiotic prophylaxis to reduce neutropenia
      related infectious complications in patients with cancer is still object to
      debate. Quinolones represent the most attractive option, since these drugs have a
      broad antimicrobial spectrum, systemic bactericidal activity, good tolerability
      and lack of myelosuppression. However, fluoroquinolone prophylaxis has already
      been associated with the emergence and spread of resistant bacteria and strictly
      precludes the subsequent use of fluoroquinolones for initial empirical therapy;
      in addition, fluoroquinolones should be administered with caution among elderly
      patients, especially those with more pronounced vascular or degenerative
      impairment of the central nervous system, cardiac disease or electrolyte
      disturbances. 

PMID- 24102282
TI  - Onco-surgical management of colo-rectal liver metastases in older patients: a new
      frontier in the 3rd millennium.
AB  - Colorectal cancer (CRC) is one the most common malignant tumors in industrialized
      countries today. Over half of all cancers are currently diagnosed in elderly
      patients, and 76% of all colorectal cancer patients are diagnosed between 65 and
      85 years old. Elderly patients are less likely to undergo curative surgery, and
      less likely to be offered the option of metastasectomy when colorectal liver
      metastases (CLM) are present. Hepatic resection has become the standard care for
      the treatment of isolated CLM. However, in studies reporting resection of CLM
      only 8-20% of the patients are older than 70 years. When balancing the benefits
      of surgical resection of liver metastases against the potential risks of surgery,
      many clinicians are still reluctant to advise in favor of surgical treatment in
      the elderly. Factors other than age should also be considered when evaluating
      surgical risk in the elderly, for example, conditions such as heart disease and
      diabetes have been shown to induce life-threatening postoperative complications.
      Age alone need not be a contraindication to aggressive surgical therapy in this
      group, rather, appropriate selection criteria based on tumor characteristics and
      general medical fitness, similar to those used for younger patients, should be
      applied. 

PMID- 24102283
TI  - Geriatric evaluation of oncological elderly patients.
AB  - Cancer has a high prevalence in older age. The management of cancer in the older
      aged person is an increasingly common problem. Age may be construed as a
      progressive loss of stress tolerance, due to decline in functional reserve of
      multiple organ systems, high prevalence of comorbid conditions, limited
      socioeconomic support, reduced cognition, and higher prevalence of depression. In
      the elderly, the comorbidities and physiological changes in the pharmacokinetics
      reduce the prospective for therapy and suggest the importance of a
      multidimensional assessment of cancer patients as well as the formulation of
      predictive models of risk, in order to estimate the life expectancy and tolerance
      to treatment. The pharmacological changes of age include decreased renal
      excretion of drugs and increased susceptibility to myelosuppression, mucositis,
      cardio toxicity and neurotoxicity. The chemotherapy in patients older than 75
      years is very limited. The geriatric assessment is considered a valid tool in
      geriatric medical. It is important for two main reasons: first of all, for the
      need to distinguish the features linked to the geriatric syndromes from those
      ones which are strictly connected to the cancer pathology; secondly, for its
      potential prognostic value. 

PMID- 24102284
TI  - Hepatocellular carcinoma: beyond the boundaries of age.
AB  - Hepatocellular carcinoma (HCC) is one of the leading causes of cancer-related
      deaths worldwide, and the management of HCC has radically changed in recent
      years. Over the last few years, many elderly patients have been considered less
      amenable to effective treatments compared to younger patients, due to the
      accumulation of different diseases during their lives. This assumption has now
      been reviewed and some key points have been outlined such as the necessity of a
      careful selection of patients, which may lead to satisfactory results after the
      treatment of elderly patients with HCC. The purpose of this study was to make a
      comprehensive analysis of results from the literature concerning the multimodal
      treatment of HCC in elderly patients, analyzing the therapeutic options such as
      liver resection, ablative treatments, liver transplantation and targeted
      chemotherapy. 

PMID- 24102285
TI  - High-resolution rovibrational spectroscopy of carbon monoxide isotopologues
      isolated in solid parahydrogen.
AB  - We report high-resolution infrared absorption spectra of six different CO
      isotopologues isolated in cryogenic parahydrogen (pH2) solids. These data provide
      a stringent test for theories of nearly free molecular rotors in crystalline
      solids, such as crystal field theory, rotation-translation coupling theory, and
      the pseudorotating cage model. A gas-phase molecule rotates about its center-of
      mass (C.M.); a trapped molecule instead rotates about its "center of interaction"
      (C.I.) with the trapping cage, which may differ from the C.M. for heteronuclear
      diatomics like CO. Isotopic manipulation of CO allows the systematic variation of
      the C.M. relative to the C.I. We report remarkably good straight line correlation
      plots between the observed matrix effects and C.M. locations. Extrapolation of
      these lines to the limit of vanishing matrix effects yields an "experimental
      prediction" of the C.I. in excellent (fortuitous?) agreement with the C.I.
      calculated using a linear pH2-CO-pH2 toy model. 

PMID- 24102286
TI  - A survey of exposures related to recognized occupational contact dermatitis in
      Denmark in 2010.
AB  - BACKGROUND: Skin diseases are the most commonly recognized occupational diseases
      in Denmark, and occupational contact dermatitis (OCD) comprises ~95% of all
      cases. OBJECTIVES: To prevent occupational contact dermatitis, it is important to
      specifically identify exposures and work routines related to outbreak of the
      disease. The aim of this study was to give an overview of exposures for patients
      with occupational contact dermatitis in Denmark in 2010, and relate this to line
      of work and disease severity. MATERIAL AND METHODS: The study was a descriptive,
      register-based study including patients with recognized occupational contact
      dermatitis in Denmark in 2010. Data were obtained from the National Board of
      Industrial Injuries in Denmark, and comprised information about the skin disease
      as well as the occupation/industry of employment and exposures. RESULTS: One
      thousand five hundred and four patients, 1020 women and 484 men, were included in
      the study. Irritant contact dermatitis accounted for 70% of all cases; 68% of
      these were caused by wet work. Forty-six per cent of all patients were employed
      either in the healthcare sector, in cleaning, or as kitchen workers. Among
      contact allergies, the most common were to rubber additives from gloves and epoxy
      in patients employed in the windmill industry. CONCLUSION: The data are important
      for planning preventive efforts in the future. The workers in the healthcare
      sector, kitchen workers and cleaners constitute almost half of all cases, and
      future preventive efforts should be directed at these occupations.

PMID- 24102287
TI  - Structures and magnetism of the rare-earth orthochromite perovskite solid
      solution LaxSm1-xCrO3.
AB  - A new mixed rare-earth orthochromite series, LaxSm1-xCrO3, prepared through
      single-step hydrothermal synthesis is reported. Solid solutions (x = 0, 0.25,
      0.5, 0.625, 0.75, 0.875, and 1.0) were prepared by the hydrothermal treatment of
      amorphous mixed-metal hydroxides at 370  degrees C for 48 h. Transmission
      electron microscopy (TEM) reveals the formation of highly crystalline particles
      with dendritic-like morphologies. Rietveld refinements against high-resolution
      powder X-ray diffraction (PXRD) data show that the distorted perovskite
      structures are described by the orthorhombic space group Pnma over the full
      composition range. Unit cell volumes and Cr-O-Cr bond angles decrease
      monotonically with increasing samarium content, consistent with the presence of
      the smaller lanthanide in the structure. Raman spectroscopy confirms the
      formation of solid solutions, the degree of their structural distortion. With the
      aid of shell-model calculations the complex mixing of Raman modes below 250 cm(
      1) is clarified. Magnetometry as a function of temperature reveals the onset of
      low-temperature antiferromagnetic ordering of Cr(3+) spins with weak
      ferromagnetic component at Neel temperatures (TN) that scale linearly with unit
      cell volume and structural distortion. Coupling effects between Cr(3+) and Sm(3+)
      ions are examined with enhanced susceptibilities below TN due to polarization of
      Sm(3+) moments. At low temperatures the Cr(3+) sublattice is shown to undergo a
      second-order spin reorientation observed as a rapid decrease of susceptibility. 

PMID- 24102288
TI  - Instruction of feeding methods to Japanese pregnant women who cannot be confirmed
      as HTLV-1 carrier by western blot test.

PMID- 24102289
TI  - N-bromoimide/DBU combination as a new strategy for intermolecular allylic
      amination.
AB  - Allylic amination reactions of alkenes, with an NBP (N-bromophthalimide) or NBS
      (N-bromosuccinimide)/DBU combination, were developed, in which both internal and
      external nitrogen nucleophiles can be installed directly. Dual activation of NBS
      or NBP by DBU leads to more electrophilic bromine and more nucleophilic nitrogen
      atoms simultaneously. This protocol may provide a novel and complementary access
      to allylic amination under mild conditions. 

PMID- 24102290
TI  - Cryo-electron microscopy reveals the membrane insertion mechanism of V. cholerae
      hemolysin.
AB  - Vibrio cholerae hemolysin (HlyA) is a 65 kDa pore-forming toxin which causes
      lysis of target eukaryotic cells by forming heptameric channels in the plasma
      membrane. Deletion of the 15 kDa C-terminus beta-prism carbohydrate-binding
      domain generates a 50 kDa truncated variant (HlyA50) with 1000-fold-reduced pore
      forming activity. Previously, we showed by cryo-electron microscopy that the two
      toxin oligomers have central channels, but the 65 kDa toxin oligomer is a seven
      fold symmetric structure with bowl-, ring-, and arm-like domains, whereas the 50
      kDa oligomer is an asymmetric jar-like heptamer. In the present study, we
      determined three-dimensional(3D) structures of HlyA and HlyA50 in presence of
      erythrocyte stroma and observed that interaction of the 65 kDa toxin with the
      stroma induced a significant decrease in the height of the beta-barrel oligomer
      with a change in conformation of the ring- and arm-like domains of HlyA. These
      features were absent in interaction of HlyA50 with stroma. We propose that this
      conformational transition is critical for membrane-insertion of the toxin.

PMID- 24102292
TI  - A background color scheme for piper plots to spatially visualize hydrochemical
      patterns.
AB  - The combination of ternary diagrams of cations and anions with a central diamond
      graph make the Piper plot very useful in visualizing groundwater chemistry
      datasets. One of the major drawbacks is that it is hard to link spatial
      attributes of the dataset to the plot. In this study, we propose a background
      color scheme of the Piper plot so that spatial representations of these data can
      be colored according to their location in the Piper plot. The color scheme is
      chosen to have maximum resolution while still being perceptually uniform. The
      linking between Piper plot and maps through this color scheme allows the
      interpretation of the trends and processes deduced from the Piper plot in terms
      of the location in the aquifer, the geology, and the groundwater flow dynamics.
      The colored Piper plot is applied to a groundwater quality dataset of the
      Condamine Alluvium in Queensland, Australia. 

PMID- 24102294
TI  - Mechanics of platelet-reinforced composites assembled using mechanical and
      magnetic stimuli.
AB  - Current fabrication technologies of structural composites based on the
      infiltration of fiber weaves with a polymeric resin offer good control over the
      orientation of long reinforcing fibers but remain too cumbersome and slow to
      enable cost-effective manufacturing. The development of processing routes that
      allow for fine control of the reinforcement orientation and that are also
      compatible with fast polymer processing technologies remains a major challenge.
      In this paper, we show that bulk platelet-reinforced composites with tailored
      reinforcement architectures and mechanical properties can be fabricated through
      the directed-assembly of inorganic platelets using combined magnetic and
      mechanical stimuli. The mechanical performance and fracture behavior of the
      resulting composites under compression and bending can be deliberately tuned by
      assembling the platelets into designed microstructures. By combining high
      alignment degree and volume fractions of reinforcement up to 27 vol %, we
      fabricated platelet-reinforced composites that can potentially be made with cost
      effective polymer processing routes while still exhibiting properties that are
      comparable to those of state-of-the-art glass-fiber composites. 

PMID- 24102293
TI  - Extended access of cocaine self-administration results in tolerance to the
      dopamine-elevating and locomotor-stimulating effects of cocaine.
AB  - Tolerance to the neurochemical and psychoactive effects of cocaine after repeated
      use is a hallmark of cocaine addiction in humans. However, comprehensive studies
      on tolerance to the behavioral, psychoactive, and neurochemical effects of
      cocaine following contingent administration in rodents are lacking. We outlined
      the consequences of extended access cocaine self-administration as it related to
      tolerance to the psychomotor activating, dopamine (DA) elevating, and DA
      transporter (DAT) inhibiting effects of cocaine. Cocaine self-administration (1.5
      mg/kg/inj; 40 inj; 5 days), which resulted in escalation of first hour intake,
      caused reductions in evoked DA release and reduced maximal rates of uptake
      through the DAT as measured by slice voltammetry in the nucleus accumbens core.
      Furthermore, we report reductions in cocaine-induced uptake inhibition and a
      corresponding increase in the dose of cocaine required for 50% inhibition of DA
      uptake (Ki ) at the DAT. Cocaine tolerance at the DAT translated to reductions in
      cocaine-induced DA overflow as measured by microdialysis. In addition, cocaine
      induced elevations in locomotor activity and stereotypy were reduced, while
      rearing behavior was enhanced in animals with a history of cocaine self
      administration. Here, we demonstrate both neurochemical and behavioral cocaine
      tolerance in an extended-access rodent model of cocaine abuse, which allows for a
      better understanding of the neurochemical and psychomotor tolerance that develops
      to cocaine in human addicts. We demonstrate tolerance to the neurochemical and
      behavioral effects of cocaine following extended-access cocaine self
      administration. With respect to neurochemistry, we show reduced cocaine-induced
      dopamine uptake inhibition, an increased dose of cocaine required for 50%
      inhibition of the dopamine transporter, and reduced cocaine-induced dopamine
      overflow. In addition, we show escalation of cocaine intake and reduced cocaine
      induced locomotor activity following cocaine self-administration.

PMID- 24102295
TI  - Feasibility of gaming console exercise and its effect on endurance, gait and
      balance in people with an acquired brain injury.
AB  - OBJECTIVE: To determine feasibility of gaming console exercise and its effect on
      endurance, gait and balance in people following acquired brain injury (ABI).
      METHOD: Twenty-one people following ABI were recruited to an 8-week randomized
      cross-over trial where 4 weeks of gaming console exercise in addition to usual
      therapy and 4 weeks of usual therapy alone were received. Feasibility measures
      included compliance, session duration and adverse events. Measures included
      endurance measured using a 6-minute walk test, spatiotemporal gait parameters
      (GAITRite) and balance using Balance Outcome Measure for Elder Rehabilitation
      (BOOMER). Motivation was measured using the Change Assessment Questionnaire.
      RESULTS: Compliance with gaming console exercise was high (99%), the majority of
      sessions reached duration target (82%) and there were no adverse events. There
      were small, though non-significant increases in 6-minute walk distance (18
      metres, 95% CI = -33 to 69), gait speed (0.11 m s(-1), 95% CI = -0.18 to 0.29)
      and balance compared to after usual therapy after gaming console exercise.
      CONCLUSIONS: Gaming console exercise appears feasible in people with ABI. Four
      weeks of gaming console exercise in addition to usual therapy appears to result
      in similar improvements in endurance, gait and balance compared to usual therapy
      alone and may enhance active engagement in therapy.

PMID- 24102296
TI  - Revision and validation of Medication Adherence Reasons Scale (MAR-Scale).
AB  - BACKGROUND: Medication non-adherence is a complex phenomenon that requires
      tailored interventions to improve it. A new self-reported measure of medication
      non-adherence was previously reported based on the commonly reported reasons
      underlying non-adherence with the intention to match the items in the scale with
      tailored interventions. OBJECTIVE: The objectives were to revise the original
      Medication Adherence Reasons Scale (MAR-Scale) based on expert opinion and
      cognitive interviewing, and establish the psychometric properties of the revised
      scale. METHODS: A cross-sectional design was used in cholesterol lowering and
      asthma maintenance medications in collaboration with an integrated medical center
      in the Mountain West. In the first phase, the original MAR-Scale was revised
      based on expert opinion and cognitive interviewing. In the second phase, the
      revised MAR-Scale was tested for psychometric properties in a random sample of
      350 subjects on each medication. RESULTS: Revisions based on expert opinion
      included asking a global question about adherence in the past 7 days, simplifying
      the items and converting them into first person sentences, objective anchoring of
      the scale, and expanding the 'forgetfulness' item. Cognitive interviewing added
      one additional item to the survey. The revised MAR- Scale identified 50% of the
      cholesterol lowering respondents and 68% of the asthma maintenance respondents as
      non-adherents. An exploratory factor analysis identified four domains in the
      scale, with Cronbach's alpha ranging from 0.848-0.953 in cholesterol lowering and
      0.827-0.891 in asthma maintenance medications. The scale also exhibited
      significant correlations with few other self-reported measures, consistent with
      hypotheses. A key limitation of the study was the moderate response rate to the
      survey for both medications. CONCLUSION: The revised MAR-Scale demonstrates
      better psychometric properties than the original.

PMID- 24102297
TI  - Ventricular contractility and compliance measured during axial flow blood pump
      support: in vitro study.
AB  - End-systolic elastance and end-diastolic compliance have been used to quantify
      systolic and diastolic function of the left ventricle (LV). In this study, the
      effective end-systolic elastance, (EES )eff , end-systolic volume intercept, (V0
      )eff , and end-diastolic compliance of the LV were assessed at various levels of
      left ventricular assist device (LVAD) support. We tested the hypothesis that (EES
      )eff and (V0 )eff vary as a function of LVAD speed, while compliance does not
      change. The Penn State in vitro cardiac simulator was used in two heart
      conditions (control and heart failure [HF]) with the HeartMate II axial flow
      LVAD. The LVAD speed was linearly increased from 6000 to 11 000 rpm, with 500-rpm
      increments. The end-systolic and end-diastolic pressure-volume relationships were
      estimated at each LVAD speed. Acute LVAD support itself showed pseudo-improvement
      of ventricular contractility. The (EES )eff and (V0 )eff in HF were found to be
      dependent on the LVAD speed. The effective compliance for both control and HF was
      independent of the LVAD speed. Therefore, when examining the time-course cardiac
      recovery induced by the LVAD support, LV performance should be measured
      immediately before and after LVAD support while keeping LVAD speed consistent to
      avoid potential overestimation of long-term cardiac recovery. 

PMID- 24102299
TI  - Deviation from symmetrically self-similar branching in trees predicts altered
      hydraulics, mechanics, light interception and metabolic scaling.
AB  - The West, Brown, Enquist (WBE) model derives symmetrically self-similar branching
      to predict metabolic scaling from hydraulic conductance, K, (a metabolism proxy)
      and tree mass (or volume, V). The original prediction was Kalpha V(0.75). We ask
      whether trees differ from WBE symmetry and if it matters for plant function and
      scaling. We measure tree branching and model how architecture influences K, V,
      mechanical stability, light interception and metabolic scaling. We quantified
      branching architecture by measuring the path fraction, Pf : mean/maximum trunk-to
      twig pathlength. WBE symmetry produces the maximum, Pf = 1.0. We explored tree
      morphospace using a probability-based numerical model constrained only by
      biomechanical principles. Real tree Pf ranged from 0.930 (nearly symmetric) to
      0.357 (very asymmetric). At each modeled tree size, a reduction in Pf led to:
      increased K; decreased V; increased mechanical stability; and decreased light
      absorption. When Pf was ontogenetically constant, strong asymmetry only slightly
      steepened metabolic scaling. The Pf ontogeny of real trees, however, was 'U'
      shaped, resulting in size-dependent metabolic scaling that exceeded 0.75 in small
      trees before falling below 0.65. Architectural diversity appears to matter
      considerably for whole-tree hydraulics, mechanics, photosynthesis and potentially
      metabolic scaling. Optimal architectures likely exist that maximize carbon gain
      per structural investment.

PMID- 24102298
TI  - Turn up the power - pharmacological activation of mitochondrial biogenesis in
      mouse models.
AB  - The oxidative phosphorylation (OXPHOS) system in mitochondria is responsible for
      the generation of the majority of cellular energy in the form of ATP. Patients
      with genetic OXPHOS disorders form the largest group of inborn errors of
      metabolism. Unfortunately, there is still a lack of efficient therapies for these
      disorders other than management of symptoms. Developing therapies has been
      complicated because, although the total group of OXPHOS patients is relatively
      large, there is enormous clinical and genetic heterogeneity within this patient
      population. Thus there has been a lot of interest in generating relevant mouse
      models for the different kinds of OXPHOS disorders. The most common treatment
      strategies tested in these mouse models have aimed to up-regulate mitochondrial
      biogenesis, in order to increase the residual OXPHOS activity present in affected
      animals and thereby to ameliorate the energy deficiency. Drugs such as
      bezafibrate, resveratrol and AICAR target the master regulator of mitochondrial
      biogenesis PGC-1alpha either directly or indirectly to manipulate mitochondrial
      metabolism. This review will summarize the outcome of preclinical treatment
      trials with these drugs in mouse models of OXPHOS disorders and discuss similar
      treatments in a number of mouse models of common diseases in which pathology is
      closely linked to mitochondrial dysfunction. In the majority of these studies the
      pharmacological activation of the PGC-1alpha axis shows true potential as
      therapy; however, other effects besides mitochondrial biogenesis may be
      contributing to this as well.

PMID- 24102300
TI  - Filaggrin loss-of-function mutations and atopic dermatitis as risk factors for
      hand eczema in apprentice nurses: part II of a prospective cohort study.
AB  - BACKGROUND/OBJECTIVES: Environmental exposure and personal susceptibility both
      contribute to the development of hand eczema. In this study, we investigated the
      effect of loss-of-function mutations in the filaggrin gene (FLG), atopic
      dermatitis and wet work exposure on the development of hand eczema in apprentice
      nurses. METHODS: Dutch apprentice nurses were genotyped for the four most common
      FLG mutations; atopic dermatitis and hand eczema history were assessed by
      questionnaire. Exposure and hand eczema during traineeships were assessed with
      diary cards. RESULTS: The prevalence of hand eczema during traineeships was
      higher among subjects with a history of hand eczema reported at inclusion. Hand
      washing during traineeships and at home increased the risk of hand eczema. After
      adjustment for the effects of exposure and FLG mutations, an odds ratio of 2.5
      (90% confidence interval 1.7-3.7) was found for a history of atopic dermatitis.
      In this study, an increased risk of hand eczema conferred by FLG mutations could
      not be shown, but subjects with concomitant FLG mutations and atopic dermatitis
      showed the highest risk of hand eczema during traineeships. CONCLUSION: A history
      of atopic dermatitis, a history of hand eczema and wet work exposure were the
      most important factors increasing the risk of hand eczema during traineeships.

PMID- 24102301
TI  - Effectiveness of melatonin for sleep impairment post paediatric acquired brain
      injury: evidence from a systematic review.
AB  - OBJECTIVE: To retrieve and review all the relevant literature describing the
      administration of melatonin to treat impaired sleep in children following
      acquired brain injury (ABI). METHODS: A systematic search and retrieval of the
      literature was conducted using advanced search techniques. The retrieval
      identified 589 papers, seven of which were relevant. Review/outcomes criteria
      were developed and study quality was determined. RESULTS: There is paucity of
      high-quality evidence to support use of melatonin for sleep impairment post
      paediatric ABI. Variation in dosage, screening and outcome measures, data
      reporting and a lack of impairment delineation and treatment stratification were
      recurrent themes. CONCLUSION: Retrieved evidence for the effectiveness of
      melatonin for post paediatric ABI sleep impairment appears promising. There is a
      clear need for further study in this area to inform clinical and research
      practices. Recommendations are given.

PMID- 24102302
TI  - Expression of platelet-bound stromal-cell derived factor-1 (SDF-1) and number of
      CD34(+) progenitor cells in patients with congestive heart failure.
AB  - Platelet-bound stromal cell-derived factor-1 (SDF-1) plays a crucial role in
      attachment of circulating CD34(+) progenitor cells to the vascular wall,
      facilitating tissue healing after injury. However there is no evidence about
      expression of platelet-bound SDF-1 in patients with congestive heart failure
      (CHF). The aim of our study was to evaluate expression of platelet-bound SDF-1
      and number of CD34(+) progenitor cells in patients with CHF. Forty-eight patients
      with idiopathic dilated cardiomyopathy (DCM) and 61 patients with ischaemic
      cardiomyopathy (ICM) were consecutively enrolled into the study. Blood taken from
      109 consecutive patients was studied for surface expression of platelet-bound SDF
      1 and number of CD34(+) progenitor cells by flow cytometry. The highest
      expression of platelet-bound SDF-1 was observed in patients with severe
      impairment of left ventricular systolic function compared with patients with mild
      or moderate impairment of left ventricular systolic function (mild vs. moderate
      vs. severe impairment of left ventricular systolic function: MFI +/- SD: 35.6 +/-
      34 vs. 101.45 +/- 73 vs. 124.86 +/- 86.7, Kruskal-Wallis p < 0.001). Similar to
      platelet-bound SDF-1 number of CD34(+) progenitor cells was the highest in severe
      impairment of left ventricular systolic function (mild vs. moderate vs. severe
      impairment of left ventricular systolic function: mean +/- SD: 260.4 +/- 177.5
      vs. 580.7 +/- 340.5 vs. 640.82 +/- 370.6, Kruskal-Wallis p < 0.001). Platelet
      bound SDF-1 expression was associated with number of circulating CD34(+)
      progenitor cells (r = 0.454, p < 0.001) in patients with CHF. Expression of
      platelet-bound SDF-1 and number of CD34(+) cells were higher in patients with DCM
      compared with patients with ICM (p < 0.001 for both) and inversely correlated
      with age and aspirin therapy. Platelet-bound SDF-1 and CD34(+) progenitor cells
      are especially increased in patients with severe impairment of left ventricular
      systolic function in CHF.

PMID- 24102303
TI  - Rhodium(III)-amine dual catalysis for the oxidative coupling of aldehydes by
      directed C-H activation: synthesis of phthalides.
AB  - A novel oxidative coupling of aldehydes to form C3-substituted phthalides
      facilitated by co-operative dual catalysis of a Rh(III) complex and an aryl amine
      is reported. The reaction involves a cascade ortho C-H activation-insertion
      annulation sequence. This methodology is efficient and applicable for the homo-
      and heterocoupling of various functionalized aldehydes generating the
      corresponding phthalides in moderate to high yields. 

PMID- 24102305
TI  - Review article: the assessment and management of chronic severe gastrointestinal
      dysmotility in adults.
AB  - BACKGROUND: The characterisation and management of chronic severe
      gastrointestinal (GI) dysmotility are challenging. It may cause intestinal
      failure requiring home parenteral nutrition (HPN). AIMS: To review the
      presentation, aetiology, characterisation, management and outcome of chronic
      severe GI dysmotility, and to suggest a pragmatic management algorithm. METHODS:
      PubMed search was performed up to December 2012 using appropriate search terms,
      restricted to human articles and reviewed for relevance. Segmental dysmotility,
      acute ileus, functional syndromes and non-English articles were excluded.
      Evidence and recommendations were evaluated using the GRADE system. RESULTS: In
      total, 721 relevant articles were reviewed. A coherent and definitive picture is
      hampered by overlapping classification systems using multi-modal characterisation
      methods, subject to pitfalls and some requiring further validation. The
      literature is confined to case series with no randomised trials. Fewer than 20%
      undergo full thickness jejunal biopsy, which are otherwise labelled idiopathic.
      However, in studies with up to 80% biopsy rates, neuromuscular abnormalities may
      be found in 90%. Between 14% and 50% will require HPN, comprising 8-14% of all
      HPN patients, of which 2/3 are primary/idiopathic and 1/3 secondary, with
      scleroderma being the leading secondary cause. Ten-year  mortality ranges from
      13% to 35% and is worst in elderly scleroderma patients. Management includes
      limited treatments for secondary causes, prokinetics, symptom palliation,
      psychological support, nutrition, hydration and judicious surgery. CONCLUSIONS:
      Severe dysmotility often remains idiopathic. It is rarely possible to alter
      disease trajectory; consequently, prognosis may be poor. Multi-disciplinary teams
      in a specialist setting can improve outcomes. Graded recommendations are
      enumerated and a pragmatic algorithm is suggested.

PMID- 24102306
TI  - Stores and Stores reply.

PMID- 24102307
TI  - Vibrational frequencies and spectroscopic constants for 1 3A' HNC and 1 3A' HOC+
      from high-accuracy quartic force fields.
AB  - The spectroscopic constants and vibrational frequencies for the 1 (3)A' states of
      HNC, DNC, HOC(+), and DOC(+) are computed and discussed in this work. The
      reliable CcCR quartic force field based on high-level coupled cluster ab initio
      quantum chemical computations is exclusively utilized to provide the anharmonic
      potential. Then, second-order vibrational perturbation theory and vibrational
      configuration interaction methods are employed to treat the nuclear Schrodinger
      equation. Second-order perturbation theory is also employed to provide
      spectroscopic data for all molecules examined. The relationship between these
      molecules and the corresponding 1 (3)A' HCN and HCO(+) isomers is further
      developed here. These data are applicable to laboratory studies involving
      formation of HNC and HOC(+) as well as astronomical observations of chemically
      active astrophysical environments. 

PMID- 24102308
TI  - Ferritin: the protein nanocage and iron biomineral in health and in disease.
AB  - At the center of iron and oxidant metabolism is the ferritin superfamily: protein
      cages with Fe(2+) ion channels and two catalytic Fe/O redox centers that initiate
      the formation of caged Fe2O3.H2O. Ferritin nanominerals, initiated within the
      protein cage, grow inside the cage cavity (5 or 8 nm in diameter). Ferritins
      contribute to normal iron flow, maintenance of iron concentrates for iron
      cofactor syntheses, sequestration of iron from invading pathogens, oxidant
      protection, oxidative stress recovery, and, in diseases where iron accumulates
      excessively, iron chelation strategies. In eukaryotic ferritins, biomineral
      order/crystallinity is influenced by nucleation channels between active sites and
      the mineral growth cavity. Animal ferritin cages contain, uniquely, mixtures of
      catalytically active (H) and inactive (L) polypeptide subunits with varied rates
      of Fe(2+)/O2 catalysis and mineral crystallinity. The relatively low mineral
      order in liver ferritin, for example, coincides with a high percentage of L
      subunits and, thus, a low percentage of catalytic sites and nucleation channels.
      Low mineral order facilitates rapid iron turnover and the physiological role of
      liver ferritin as a general iron source for other tissues. Here, current concepts
      of ferritin structure/function/genetic regulation are discussed and related to
      possible therapeutic targets such as mini-ferritin/Dps protein active sites
      (selective pathogen inhibition in infection), nanocage pores (iron chelation in
      therapeutic hypertransfusion), mRNA noncoding, IRE riboregulator (normalizing the
      ferritin iron content after therapeutic hypertransfusion), and protein
      nanovessels to deliver medicinal or sensor cargo. 

PMID- 24102310
TI  - Two unique phosphorylation-driven signaling pathways crosstalk in Staphylococcus
      aureus to modulate the cell-wall charge: Stk1/Stp1 meets GraSR.
AB  - The Stk1/Stp1 and GraSR signal-transduction pathways are two distinct pathways in
      Staphylococcus aureus that rely on a reversible phosphorylation process in
      transducing external stimuli intracellularly. Stk1/Stp1 is an eukaryote-like
      Ser/Thr kinase phosphatase pair involved in purine biosynthesis, cell-wall
      metabolism, and autolysis. GraSR is a two-component system involved in resistance
      to cationic antimicrobial peptides. Both systems are implicated in S. aureus
      virulence and resistance to cell-wall inhibitors. Our study shows that the
      response regulator protein GraR undergoes phosphorylation by Stk1 at three
      threonine residues in the DNA-binding domain. Phosphorylation by Stk1 depends on
      the structural integrity of GraR as well as the amino acid sequences flanking the
      phosphorylation sites. Its homologue in Bacillus subtilis , BceR, which harbors
      two of the three phosphorylation sites in GraR, does not undergo Stk1-dependent
      phosphorylation. GraR is involved in regulation of the dltABCD operon, the gene
      products of which add the d-Ala on wall teichoic acid (WTA). Investigation of WTA
      isolated from the S. aureus RN6390 DeltagraR strain by NMR spectroscopy showed a
      clear negative effect that graR deletion has on the d-Ala content of WTA.
      Moreover, complementation of DeltagraR mutant with graR lacking the Stk1
      phosphorylation sites mirrors this effect. These findings provide evidence that
      GraR is a target of Stk1 in vivo and suggest that modification of WTA by d-Ala is
      modulated by Stk1. The crosstalk between these two otherwise independent
      signaling pathways may facilitate S. aureus interaction with its environment to
      modulate processes such as cell growth and division and virulence. 

PMID- 24102311
TI  - Aromatase excess syndrome in a family with upstream deletion of CYP19A1.

PMID- 24102312
TI  - Synthesis and characterization of palladium and palladium-cobalt nanoparticles on
      Vulcan XC-72R for the oxygen reduction reaction.
AB  - A single-source approach was used to synthesize bimetallic nanoparticles on a
      high-surface-area carbon-support surface. The synthesis of palladium and
      palladium-cobalt nanoparticles on carbon black (Vulcan XC-72R) by chemical and
      thermal reduction using organometallic complexes as precursors is described. The
      electrocatalysts studied were Pd/C, Pd2Co/C, and PdCo2/C. The nanoparticles
      composition and morphology were characterized using inductively coupled plasma
      mass spectrophotometer (ICP-MS), X-ray photoelectron spectroscopy (XPS), energy
      dispersive X-ray fluorescence spectroscopy (EDS), X-ray diffraction (XRD), and
      transmission electron microscopy (TEM) techniques. Electrocatalytic activity
      towards the oxygen reduction reaction (ORR) and methanol tolerance in oxygen
      saturated acid solution were determined. The bimetallic catalyst on carbon
      support synthetized by thermal reduction of the Pd2Co precursor has ORR
      electrocatalytic activity and a higher methanol tolerance than a Pt/C catalyst. 

PMID- 24102313
TI  - The potential of acridine carboxamide Pt complexes as anti-cancer agents : a
      review.
AB  - There has been a concerted attempt to produce more effective anti-tumour agents
      based on the widely-used cancer chemotherapeutic agent, cisplatin. One
      interesting approach is to attach a DNA-affinic chemical group to the cisplatin
      molecule. This could result in a more efficient binding to the biological target,
      DNA, and produce a different spectrum of Pt-DNA crosslinks that may permit an
      agent to overcome cisplatin resistance. Acridine Pt complexes, have activity
      against cisplatin-resistant cells, have a differing DNA sequence selectivity
      compared to cisplatin and hence, are strong candidates for development as anti
      tumour agents. The properties of acridine Pt analogues, especially 9
      aminoacridine carboxamide Pt complexes, are reviewed here and the sequence
      specific interaction of acridine carboxamide Pt complexes with DNA is explored.
      The 9-aminoacridine carboxamide Pt complexes have a reduced reaction at runs of
      consecutive guanine nucleotides compared with cisplatin, and form adducts at
      novel DNA sequences, especially 5'-CGA. The activity of the 9-aminoacridine Pt
      complexes against cisplatin-resistant cell lines is due to their ability to
      escape the DNA repair capacity of the cells, through the production of variant
      DNA adducts. The future prospects for development of acridine carboxamide Pt
      complexes as cancer chemotherapeutic agents are discussed. 

PMID- 24102309
TI  - Neuroimaging, behavioral, and psychological sequelae of repetitive combined
      blast/impact mild traumatic brain injury in Iraq and Afghanistan war veterans.
AB  - Abstract Whether persisting cognitive complaints and postconcussive symptoms
      (PCS) reported by Iraq and Afghanistan war veterans with blast- and/or combined
      blast/impact-related mild traumatic brain injuries (mTBIs) are associated with
      enduring structural and/or functional brain abnormalities versus comorbid
      depression or posttraumatic stress disorder (PTSD) remains unclear. We sought to
      characterize relationships among these variables in a convenience sample of Iraq
      and Afghanistan-deployed veterans with (n=34) and without (n=18) a history of one
      or more combined blast/impact-related mTBIs. Participants underwent magnetic
      resonance imaging of fractional anisotropy (FA) and macromolecular proton
      fraction (MPF) to assess brain white matter (WM) integrity; [(18)F]
      fluorodeoxyglucose positron emission tomography imaging of cerebral glucose
      metabolism (CMRglu); structured clinical assessments of blast exposure,
      psychiatric diagnoses, and PTSD symptoms; neurologic evaluations; and self-report
      scales of PCS, combat exposure, depression, sleep quality, and alcohol use.
      Veterans with versus without blast/impact-mTBIs exhibited reduced FA in the
      corpus callosum; reduced MPF values in subgyral, longitudinal, and
      cortical/subcortical WM tracts and gray matter (GM)/WM border regions (with a
      possible threshold effect beginning at 20 blast-mTBIs); reduced CMRglu in
      parietal, somatosensory, and visual cortices; and higher scores on measures of
      PCS, PTSD, combat exposure, depression, sleep disturbance, and alcohol use.
      Neuroimaging metrics did not differ between participants with versus without
      PTSD. Iraq and Afghanistan veterans with one or more blast-related mTBIs exhibit
      abnormalities of brain WM structural integrity and macromolecular organization
      and CMRglu that are not related to comorbid PTSD. These findings are congruent
      with recent neuropathological evidence of chronic brain injury in this cohort of
      veterans. 

PMID- 24102314
TI  - Synthesis and structure activity relationship study of N-substituted 3,5
      diarylidenepiperidin- 4-ones as potential antitumor agents.
AB  - A new series of N-substituted diarylidenepiperidin-4-ones was synthesized and
      screened for their possible anticancer activity at the NCI Developmental
      Therapeutic Program. Almost all the synthesized compounds showed more potent
      antiproliferative activity than curcumin. The most active compound in this study
      was 3,5-bis(4-bromobenzylidene)-1-propanoylpiperidin-4-one (8a) with MG-MID GI50,
      TGI, and LC50 values of 0.35, 1.62 and 9.12 uM, respectively. Compound 8a
      displayed broad spectrum antiproliferative activity with GI50 values below 1 uM
      in 81% of the tested cell lines and was found to be two folds more potent than EF
      24. A detailed study of the structure activity relationship of the N-substitution
      was also described.

PMID- 24102315
TI  - Targetability and biodistribution of radioiodinated hypericin: comparison between
      microdosing and carrier-added preparations.
AB  - OBJECTIVES: To study the effect of co-injecting unlabelled hypericin (Hyp) on
      biodistribution, necrosis uptake and tumour retention of iodine-123 or iodine-131
      labelled hypericin ((123/131)I-Hyp), a necrosis avid agent for an anticancer
      radiotherapy. METHODS: (123/131)I-Hyp was prepared with Iodogen as oxidant and
      formulated in 0.6 MUg/kg no-carrier-added (NCA) or 0.25 mg/kg unlabelled Hyp
      carrier-added (CA) forms using dimethyl sulfoxide/polyethylene glycol
      400/propylene glycol/water (25/25/25/25% v/v/v/v), as solvent mixture.
      Comparisons on biodistribution and necrosis uptake of NCA and CA(123)I-Hyp were
      conducted on rats (n=24) of reperfused liver infarction (RPLI) in 48h p.i. Tumour
      retention of CA(131)I-Hyp was assessed in severe combined immunodeficiency (SCID)
      mice with fibrosarcoma (RIF-1) tumours (n=25) over 40 days. To cause intratumour
      necrosis, mice were pre-treated with a vascular disrupting agent CA4P at 10mg/kg.
      Tissue-gamma counting (TGC), autoradiography and histology were performed.
      RESULTS: TGC revealed no significant difference in organ biodistribution between
      RPLI-rats injected with NCA and CA(123)I-Hyp, except in intestines, liver, lungs
      and stomach (P<0.05). Both preparations showed hepatobiliary excretion since
      intestines and faeces retained the most radioactivity. NCA and CA(123)I-Hyp
      exhibited high avidity and selectivity for hepatic infarction. From the day after
      injection onward, CA(123)I-Hyp showed greater target accumulation (7-11%ID/g)
      than (123)I-Hyp alone (~4%ID/g; P<0.05). In RIF-1-SCID mice receiving CA(131)I
      Hyp, prolonged high retention in tumour necrosis was detected over 40 days p. i.
      TGC findings were confirmed by histological and autoradiographic analysis.
      CONCLUSIONS: The study demonstrated the co-injection of unlabelled Hyp affected
      necrosis uptake but almost no biodistribution of radioiodinated Hyp. Long-term
      high retention into tumour necrosis characterizes the carrier-added (131)I-Hyp.

PMID- 24102316
TI  - Association of third-trimester abdominal circumference with provider-initiated
      preterm delivery.
AB  - OBJECTIVE: Evaluate the association of a small third-trimester abdominal
      circumference (AC < 10th percentile) in the setting of a normal estimated fetal
      weight (EFW >= 10th percentile) with gestational age at delivery, indication for
      delivery and neonatal outcomes. METHODS: Retrospective cohort study at an
      academic hospital of women with singleton pregnancy seen for ultrasound from 28+0
      33+6 weeks of gestation during 2009-2011. Outcomes were compared between two
      groups: normal AC (AC and EFW >= 10th percentile) and small AC (AC < 10th
      percentile and EFW >= 10th percentile). RESULTS: Among 592 pregnancies, fetuses
      in the small AC group (n = 55) experienced a higher incidence of overall preterm
      delivery (RR: 2.2, 95% CI: 1.3-3.7) and provider-initiated preterm delivery (RR:
      3.7, CI: 1.8-7.5) compared to those in the normal AC group (n = 537). Neonates in
      the small AC group had a lower median birth weight whether delivered at term (p <
      0.001) or preterm (p = 0.04), but were not more likely to experience intensive
      care unit admission or respiratory distress syndrome (all p >= 0.35).
      CONCLUSIONS: Small AC, even in the setting of an EFW >= 10th percentile, was
      associated with a higher incidence of overall and provider-initiated preterm
      delivery despite similar neonatal outcomes. Further investigation is warranted to
      determine whether these preterm deliveries could be prevented.

PMID- 24102317
TI  - Use of an educational support program to assist patients receiving injectable
      osteoporosis treatment: experience with teriparatide.
AB  - OBJECTIVE: Low treatment adherence and persistence are important considerations
      in the management of chronic disorders such as osteoporosis, as they are linked
      to the reduced effectiveness of drug therapy. As teriparatide (Forsteo, Eli Lilly
      and Company, Alcobendas, Spain) is administered by subcutaneous injection using a
      customized delivery device for 24 months to reduce fracture risk in patients with
      osteoporosis, an educational support program was developed to assist patients
      with correctly administering the treatment. METHODS: All patients in Spain can
      voluntarily participate in this ongoing program, which consists of up to 22 phone
      calls, by a qualified and licensed nurse trained in use of the delivery device,
      that are designed to improve patients' knowledge of, and to provide a reminder as
      to how to use, the device. Patients are also sent educational material regarding
      the delivery device and osteoporosis, and regularly receive needles suitable for
      the device. This study presents persistence data for all 23,069 patients
      registered in the program and prescribed teriparatide between September 2007 and
      June 2010. RESULTS: Persistence in the program was 90.8% at 3 months, 83.5% at 6
      months, 74.8% at 12 months, 68.5% at 18 months, and 64.1% at 24 months. Patient
      satisfaction with the educational support program was high at all assessment
      times, and patients generally found the delivery device easy to use. CONCLUSIONS:
      These results show that patients from all provinces in Spain with severe
      osteoporosis receiving teriparatide and enrolled in an educational support
      program had high persistence and satisfaction with the program. However, no
      control group was included in these analyses and it is possible that selection
      bias occurred. It is suggested that patient-based strategies similar to this
      could be beneficial for all long-term treatments.

PMID- 24102318
TI  - Combination of high on-treatment platelet aggregation and low deaggregation
      better predicts long-term cardiovascular events in PCI patients under dual
      antiplatelet therapy.
AB  - High on-treatment platelet reactivity is associated with short-term major
      cardiovascular (CV) events in patients undergoing percutaneous coronary
      intervention (PCI). Maximum and final aggregation assessed by light transmission
      aggregometry (LTA) have both been used to predict short-term outcome after PCI,
      however their long-term prognostic impact remains controversial. There is
      currently no information regarding the prognostic role of deaggregation and its
      added value in combination with established aggregation parameters. About 1279
      patients with symptomatic coronary artery disease (CAD) undergoing PCI were
      enrolled in this monocentric study. On-treatment platelet aggregation under
      clopidogrel maintenance therapy, as well as deaggregation was determined by
      maximum and final aggregation (5 min after adding of the agonist). Deaggregation
      was defined as slope of the tangent between Aggmax +0.5 min. Primary endpoints
      were the composite of myocardial infarction, stroke, and CV death or stent
      thrombosis according to the ARC criteria. Low deaggregation, defined as values in
      the lowest tertile (<1.5), was more frequent in patients with acute coronary
      syndromes (ACS) compared to patients with stable angina pectoris (SAP), ACS:
      29.6% vs. SAP: 22.0%, p = 0.001. The combination of high on-treatment platelet
      reactivity, defined by the upper tertile of Aggmax and low deaggregation, was
      associated with significantly increased risk for combined long-term CV events.
      The combination of low deaggregation and high on-treatment platelet reactivity is
      associated with higher risk for recurrent events in patients with CAD undergoing
      PCI. Thus, deaggregation might be a more sensitive parameter providing added
      value in terms of risk prediction for long-term recurrent CV events in relation
      with established aggregation parameters.

PMID- 24102320
TI  - A novel iron transporter in Streptococcus iniae.
AB  - Streptococcus iniae is a major pathogen that results in considerable economic
      loss to fish farms. Restricted availability of iron is a huge obstacle to
      survival for pathogenic bacteria during infection, and iron acquisition is
      important in bacterial virulence. In this study, S. iniae HD-1 was shown not to
      produce siderophores (low-molecular-weight compounds) but rather to require iron
      containing proteins for growth under iron-restricted conditions. The adenosine
      triphosphate (ATP)-binding-cassette (ABC) transporter system (ftsABCD), which is
      cotranscribed by four downstream genes, namely, ftsA, ftsB, ftsC and ftsD, was
      identified as responsible for haem utilization of S. iniae. Analysis of the
      corresponding recombinant protein, FtsB, indicated that it is a putative
      lipoprotein which plays a role in haem utilization and is produced in vivo during
      infection with S. iniae HD-1, and therefore may be a potential candidate antigen
      for a streptococcal vaccine. 

PMID- 24102321
TI  - Assessment of aortic valve opening during rotary blood pump support using pump
      signals.
AB  - During left ventricular support by rotary blood pumps (RBPs), the biomechanics of
      the aortic valve (AV) are altered, potentially leading to adverse events like
      commissural fusion, valve insufficiency, or thrombus formation. To avoid these
      events, assessment of AV opening and consequent adaptation of pump speed seem
      important. Additionally, this information provides insight into the heart-pump
      interaction. The aim of this study was to develop a method to assess AV opening
      from the pump flow signal. Data from a numerical model of the cardiovascular
      system and animal experiments with an RBP were employed to detect the AV opening
      from the flow waveform under different hemodynamic conditions. Three features
      calculated from the pump flow waveform were used to classify the state of the AV:
      skewness, kurtosis, and crest factor. Three different classification algorithms
      were applied to determine the state of the AV based on these features. In the
      model data, the best classifier resulted in a percentage of correctly identified
      beats with a closed AV (specificity) of 99.9%. The percentage of correctly
      identified beats with an open AV (sensitivity) was 99.5%. In the animal
      experiments, specificity was 86.8% and sensitivity reached 96.5%. In conclusion,
      a method to detect AV opening independently from preload, afterload, heart rate,
      contractility, and degree of support was developed. This algorithm makes the
      evaluation of the state of the AV possible from pump data only, allowing pump
      speed adjustment for a frequent opening of the AV and providing information about
      the interaction of the native heart with the RBP. 

PMID- 24102322
TI  - Consistency of return to normal function, productivity, and satisfaction
      following migraine attacks treated with sumatriptan/naproxen sodium combination.
AB  - OBJECTIVES: To assess the consistency of improved functioning, productivity, and
      medication satisfaction in migraines treated with a single tablet of sumatriptan
      85 mg/naproxen sodium 500 mg (S/NS) using an early intervention approach.
      METHODS: Two randomized, double-blind, placebo-controlled, 4-period crossover,
      multi-attack, multi-center, outpatient studies of moderate to severe adult
      migraineurs were conducted to compare S/NS with placebo. Participants recorded
      outcome assessments in a diary during the 24 hours following study medication.
      Analyses were conducted on the intent-to-treat population who treated at least 1
      attack. Statistical significance between treatment groups used analysis of
      variance repeated measures models and the intent-to-treat population. There were
      no corrections for multiplicity. RESULTS: Almost half (48.5%) of migraineurs
      treated with S/NS returned to normal functioning at 2 hours and 73.3% at 4 hours
      postdose, compared with 28.7% (2 hours) and 43.3% (4 hours) of placebo-treated
      attacks. Total productivity loss over the 24 hours postdose was significantly
      reduced following S/NS treatment (2.5 hours on average) compared with placebo
      (4.0 hours). Sumatriptan/naproxen treatment resulted in significantly higher
      medication satisfaction scores on the efficacy, functionality, and total efficacy
      subscales compared with placebo in all attacks in both studies.
      Sumatriptan/naproxen treatment also provided significantly greater ease of use in
      7 of the 8 attacks. Although tolerability was high in both treatment groups (over
      90%), the placebo group was significantly less bothered by side effects in 6 of 8
      attacks. CONCLUSION: Results from these 2 randomized, double-blind, placebo
      controlled, multi-attack, crossover studies demonstrated the rapid and consistent
      restoration of patients' functioning, the consistent reduction in productivity
      loss, and high satisfaction ratings from patients treating multiple migraine
      attacks with S/NS using an early intervention approach.

PMID- 24102323
TI  - Discontinued drugs in 2012: oncology drugs.
AB  - This year's analysis of discontinued drugs in oncology reports on 29 drugs
      dropped from the global pipeline in 2012. Similar to the trends that were
      observed in 2011, there were a large number (13) of Phase I terminations
      reported, largely due to strategic or unspecified reasons. Only one of these
      Phase I discontinued drugs appeared to incorporate a patient stratification
      biomarker in the study design and only four studies incorporated pharmacodynamic
      biomarker analysis. Out of seven drugs failing in Phase III, six were reported to
      display a lack of efficacy. None of the Phase III studies investigating these
      agents incorporated stratification biomarkers in the trial design. The aim of
      this article is to highlight the cohort of drugs discontinued in 2012 and discuss
      their profile in the context of the evolving paradigm for anticancer drug
      development. It is noteworthy that while there is clearly still room for
      improvement in the efficiency of drug development, increased collaboration among
      academics, industry, regulators, government and not-for-profit organisations
      appears to be contributing to increased numbers of new drug approvals. 

PMID- 24102325
TI  - The circadian clock has transient plasticity of period and is required for timing
      of nocturnal processes in Arabidopsis.
AB  - A circadian rhythm matched to the phase and period of the day-night cycle has
      measurable benefits for land plants. We assessed the contribution of circadian
      period to the phasing of cellular events with the light : dark cycle. We also
      investigated the plasticity of circadian period within the Arabidopsis circadian
      oscillator. We monitored the circadian oscillator in wild-type and circadian
      period mutants under light : dark cycles of varying total duration. We also
      investigated changes in oscillator dynamics during and after the transition from
      light : dark cycles to free running conditions. Under light : dark cycles, dawn
      and dusk were anticipated differently when the circadian period was not resonant
      with the environmental period ('T cycle'). Entrainment to T cycles differing from
      the free-running period caused a short-term alteration in oscillator period. The
      transient plasticity of period was described by existing mathematical models of
      the Arabidopsis circadian network. We conclude that a circadian period resonant
      with the period of the environment is particularly important for anticipation of
      dawn and the timing of nocturnal events; and there is short-term and transient
      plasticity of period of the Arabidopsis circadian network.

PMID- 24102324
TI  - Context matters: community characteristics and mental health among war-affected
      youth in Sierra Leone.
AB  - BACKGROUND: Worldwide, over one billion children and adolescents live in war
      affected settings. At present, only limited research has investigated linkages
      between disrupted social ecology and adverse mental health outcomes among war
      affected youth. In this study, we examine three community-level characteristics -
      social disorder and collective efficacy within the community, as reported by
      caregivers, and perceived stigma as reported by youth - in relation to
      externalizing behaviors and internalizing symptoms among male and female former
      child soldiers in postconflict Sierra Leone. METHODS: A total of 243 former child
      soldiers (30% female, mean age at baseline: 16.6 years) and their primary
      caregivers participated in interviews in 2004 and 2008, as part of a larger
      prospective cohort study of war-affected youth in Sierra Leone. Two-point growth
      models were estimated to examine the relationship between community-level
      characteristics and externalizing and internalizing outcomes across the time
      points. RESULTS: Both social disorder within the community, reported by
      caregivers, and perceived stigma, reported by youth, positively covaried with
      youths' externalizing and internalizing scores - indicating that higher levels of
      each at baseline and follow-up were associated with higher levels of mental
      health problems at both time points (p < .05). The relationship between
      collective efficacy and mental health outcomes was nonsignificant (p > .05).
      CONCLUSIONS: This study offers a rare glimpse into the role that the postconflict
      social context plays in shaping the mental health among former child soldiers.
      Results indicate that both social disorder and perceived stigma within the
      community demonstrate an important relationship to externalizing and
      internalizing problems among adolescent ex-combatants. Moreover, these
      relationships persisted over a 4-year period of follow-up. These results
      underscore the importance of the postconflict social environment and the need to
      develop postconflict interventions that address community-level processes in
      addition to the needs of families and individuals.

PMID- 24102326
TI  - Biphasic magnetic nanoparticles-nanovesicle hybrids for chemotherapy and self
      controlled hyperthermia.
AB  - AIM: The aim was to develop magnetic nanovesicles for chemotherapy and self
      controlled hyperthermia that prevent overheating of tissues. MATERIALS & METHODS:
      Magnetic nanovesicles containing paclitaxel and a dextran-coated biphasic
      suspension of La0.75Sr0.25MnO3 and Fe3O4 nanoparticles (magnetic nanoparticles)
      were developed. RESULTS: Encapsulation efficiencies of magnetic nanoparticles and
      paclitaxel were 67 +/- 5 and 83 +/- 3%, respectively. Sequential release
      performed at 37 degrees C for 1 h followed by 44 degrees C for another 1 h (as
      expected for intratumoral injection), showed a cumulative release of 6.6% (109.6
      ug), which was above the IC50 of the drug. In an alternating current magnetic
      field, the temperature remained controlled at 44 degrees C and a synergistic
      cytotoxicity of paclitaxel and hyperthermia was observed in MCF-7 cells.
      CONCLUSION: Magnetic nanovesicles containing biphasic suspensions
      La0.75Sr0.25MnO3 and Fe3O4 nanoparticles encapsulating paclitaxel have potential
      for combined self-controlled hyperthermia and chemotherapy.

PMID- 24102327
TI  - 3D presentation of a neurotrophic factor for the regulation of neural progenitor
      cells.
AB  - BACKGROUND: Adequate cell-scaffold interactions and neurotrophin support are
      essential factors for neural regeneration. AIM: To provide insight into the
      biofunctionalization of complex 3D scaffolds with nanoscale precision, as well as
      the effect of spatial distribution of brain-derived neurotrophic factor (BDNF)
      and its prolonged stimulation in combination with enhanced cell affinity of
      nanofibrous scaffolds on the survival/proliferation and neurite outgrowth.
      METHODS & MATERIALS: We developed a versatile approach using layer-by-layer self
      assembly to incorporate cell adhesion and spatial representation of neurotrophic
      factors into complex nanofibrous scaffolds. RESULTS: Heparin/poly-L-lysine (PLL)
      polyelectrolyte multilayers (PEMs) were deposited on electrospun poly-epsilon
      caprolatone nanofibers. Well-controlled amounts of BDNF were immobilized on the
      PEM-modified nanofibers. In addition, longer neurite outgrowth was observed in
      neural progenitor cells cultured on PLL-terminating PEM scaffolds. The
      immobilized BDNF on PLL-terminated PEM scaffolds resulted in significantly longer
      neurites and higher cell numbers (p < 0.01) compared with BDNF-free and BDNF
      adsorbed PLL-terminating scaffolds. Interestingly, there was no upregulation of
      TrkB-FL, TrkB-T1 or GAP-43 mRNAs with immobilized BDNF in day 5 cultures.
      DISCUSSION & CONCLUSION: This work reinforces the importance of the combinatorial
      effects of biomaterial scaffold nanostructure and spatial presentation of
      neurotrophins in directing neural progenitor cell fates.

PMID- 24102328
TI  - Magnetic layer-by-layer coated particles for efficient MRI of dendritic cells and
      mesenchymal stem cells.
AB  - AIM: Cell detection by MRI requires high doses of contrast agent for generating
      image contrast. Therefore, there is a constant need to develop improved systems
      that further increase sensitivity, and which could be used in clinical settings.
      In this study, we devised layer-by-layer particles and tested their potential for
      cell labeling. MATERIALS & METHODS: The advantages of layer-by-layer technology
      were exploited to obtain magnetic particles of controllable size, surface
      chemistry and magnetic payload. RESULTS: Flexibility in size and surface charge
      enabled efficient intracellular delivery of magnetic particles in mesenchymal
      stem cells and dendritic cells. Owing to the high magnetic payload of the
      particles, high MRI contrast was generated, even for very low cell numbers.
      Subcutaneous injection of the particles and subsequent uptake by dendritic cells
      enabled clear visualization of dendritic cells homing towards nearby lymph nodes
      in mice. CONCLUSION: The magnetic particles offer several possibilities as
      efficient cellular MRI contrast agents for direct in vitro or in vivo cell
      labeling.

PMID- 24102329
TI  - The development and validation of the treatment of autoimmune bullous disease
      quality of life questionnaire, a tool to measure the quality of life impacts of
      treatments used in patients with autoimmune blistering disease.
AB  - BACKGROUND: Treatments for autoimmune blistering diseases have significant risk
      of medical complications and quality of life impacts during treatment, and it is
      difficult to differentiate these impacts from disease burden or the effects of
      treatment. OBJECTIVES: To develop a quality of life instrument specific to the
      effects of treatments used in patients with autoimmune bullous disease (AIBD).
      METHODS: A comprehensive item generation process was used to build a 45-item
      pilot Autoimmune Bullous Disease Quality of Life (ABQOL) questionnaire,
      distributed to 70 patients with AIBD. Experts in bullous disease refined the
      pilot ABQOL, selecting only those questions pertaining to the treatment effects.
      This pilot Treatment of Autoimmune Bullous Disease Quality of Life (TABQOL)
      questionnaire was administered to 70 patients, before factor analysis was
      performed to yield the final questionnaire of 17 questions. Validity and
      reliability were evaluated across a range of indices. RESULTS: Face and content
      validity were established through a comprehensive patient interview process,
      expert review and summaries of treatments used. The questionnaire was found to
      have appropriate correlation with the Dermatology Life Quality Index (r = 0.64)
      and the level of treatments used (P < 0.01), and was found to be responsive to
      overall variations in treatment burden. The TABQOL was also found to be a
      reliable instrument as evaluated by internal consistency (Cronbach alpha = 0.892)
      and test-retest reliability (r = 0.99). CONCLUSIONS: We have shown that the
      TABQOL questionnaire is a valid and reliable instrument that may to be used to
      measure treatment burden in AIBD and serve as an end point in clinical trials.

PMID- 24102319
TI  - Transient receptor potential (TRP) channels: a clinical perspective.
AB  - Transient receptor potential (TRP) channels are important mediators of sensory
      signals with marked effects on cellular functions and signalling pathways.
      Indeed, mutations in genes encoding TRP channels are the cause of several
      inherited diseases in humans (the so-called 'TRP channelopathies') that affect
      the cardiovascular, renal, skeletal and nervous systems. TRP channels are also
      promising targets for drug discovery. The initial focus of research was on TRP
      channels that are expressed on nociceptive neurons. Indeed, a number of potent,
      small-molecule TRPV1, TRPV3 and TRPA1 antagonists have already entered clinical
      trials as novel analgesic agents. There has been a recent upsurge in the amount
      of work that expands TRP channel drug discovery efforts into new disease areas
      such as asthma, cancer, anxiety, cardiac hypertrophy, as well as obesity and
      metabolic disorders. A better understanding of TRP channel functions in health
      and disease should lead to the discovery of first-in-class drugs for these
      intractable diseases. With this review, we hope to capture the current state of
      this rapidly expanding and changing field.

PMID- 24102334
TI  - Fragmentation of deprotonated glycolaldehyde in the gas phase and relevance to
      the formose reaction.
AB  - From gas phase reactivity studies employing tandem mass spectrometry, the
      unimolecular dissociation of the corresponding base of glycolaldehyde has been
      probed under conditions of collisional activation. Three reactions were observed
      (in order of decreasing abundance): loss of CO, CH2O, and loss of H2. Detailed
      reaction mechanisms for each of the three reactions were obtained by quantum
      chemical calculations, and the reaction characteristics and energetics were found
      to be in good agreement with experimental observations. The relevance of these
      findings to the formose reaction and possible interstellar formation of
      carbohydrates from formaldehyde is discussed. It is concluded that the critical C
      C bond forming reaction between two formaldehyde molecules to give the
      glycoladehyde is unlikely to occur in the gas phase via a route involving the
      free formyl anion, thereby precluding a key pathway for interstellar formation of
      carbohydrates. However, an alternative formation reaction is suggested. 

PMID- 24102331
TI  - Acute alcohol intoxication, diffuse axonal injury and intraventricular bleeding
      in patients with isolated blunt traumatic brain injury.
AB  - OBJECTIVE: The influence of blood alcohol level (BAL) on outcome remains unclear.
      This study investigated the relationships between BAL, type and number of diffuse
      axonal injury (DAI), intraventricular bleeding (IVB) and 6-month outcome.
      METHODS: This study reviewed 419 patients with isolated blunt traumatic brain
      injury. First, it compared clinical and radiological characteristics between
      patients with good recovery and disability. Second, it compared BAL among DAI
      lesions. Third, it evaluated the correlation between the BAL and severity of IVB,
      number of DAI and corpus callosum injury lesions. RESULTS: Regardless of BAL,
      older age, male gender, severe Glasgow Coma Scale score (<9), abnormal pupil, IVB
      and lesion on genu of corpus callosum were significantly related to disability.
      There were no significant differences between the BAL and lesions of DAI. Simple
      regression analysis revealed that there were no significant correlation between
      BAL and severity of IVB, number of DAI and corpus callosum injury lesions.
      CONCLUSIONS: Acute alcohol intoxication was not associated with type and number
      of DAI lesion, IVB and disability. This study suggested that a specific type of
      traumatic lesion, specifically lesion on genu of corpus callosum and IVB, might
      be more vital for outcome.

PMID- 24102333
TI  - Proposed score for survival of patients with myelodysplastic syndromes.
AB  - BACKGROUND: Patient selection for various therapies in myelodysplastic syndromes
      (MDS) is based on prognostic factors, scoring systems and the individual life
      expectancy. However, most established risk scores include mainly disease-related
      parameters and thus focus on leukaemia-transformation rather than survival.
      PATIENTS AND METHODS: To establish a risk score optimized for prediction of
      survival, we analysed international prognostic scoring system (IPSS)-related and
      IPSS-independent variables in 400 patients with primary MDS (median age: 71
      years; range 18-91) of the Austrian MDS platform. Patients were randomly split
      into a learning sample (60%) and validation sample (40%). External validation was
      performed on 93 patients from the Heinrich Heine University
      (Duesseldorf/Germany). RESULTS: By multivariate analysis, IPSS, ferritin, age and
      comorbidities were found to be independent predictive variables concerning
      survival. Based on weighing these prognostic parameters against each other, we
      established a novel survival score employing IPSS, ferritin (< 900 ng/mL = 0; >=
      900 ng/mL = 1), age (< 70 years = 0; 70-79 years = 1; >= 80 years = 1.5) and HCT
      CI comorbidity (low/intermediate = 0; high = 0.5). Using this score, four
      prognostic risk groups could be discriminated in the validation sample, with
      highly significant differences in life expectancy [median survival: LowS (score
      0), not reached; Int-1S (score 0.5-1.0), 3.84 years; Int-2S (score 1.5-2.0): 2.72
      years; and HighS (score > 2.0): 0.80 years; P < 0.0001]. CONCLUSIONS: Our newly
      proposed score may be a useful tool for survival prediction in MDS and helpful in
      patient selection for various therapies in daily practice and clinical trials.

PMID- 24102330
TI  - A novel function for proSAAS as an amyloid anti-aggregant in Alzheimer's disease.
AB  - Neurodegenerative diseases such as Alzheimer's disease (AD) are characterized by
      an abnormal aggregation of misfolded beta-sheet rich proteins such as beta
      amyloid (Abeta). Various ubiquitously expressed molecular chaperones control the
      correct folding of cellular proteins and prevent the accumulation of harmful
      species. We here describe a novel anti-aggregant chaperone function for the
      neuroendocrine protein proSAAS, an abundant secretory polypeptide that is widely
      expressed within neural and endocrine tissues and which has previously been
      associated with neurodegenerative disease in various proteomics studies. In the
      brains of 12-month-old APdE9 mice, and in the cortex of a human AD-affected
      brain, proSAAS immunoreactivity was highly colocalized with amyloid pathology.
      Immunoreactive proSAAS co-immunoprecipitated with Abeta immunoreactivity in
      lysates from APdE9 mouse brains. In vitro, proSAAS efficiently prevented the
      fibrillation of Abeta(1-42) at molar ratios of 1 : 10, and this anti-aggregation
      effect was dose dependent. Structure-function studies showed that residues 97-180
      were sufficient for the anti-aggregation function against Abeta. Finally,
      inclusion of recombinant proSAAS in the medium of Neuro2a cells, as well as
      lentiviral-mediated proSAAS over-expression, blocked the neurocytotoxic effect of
      Abeta(1-42) in Neuro2a cells. Taken together, our results suggest that proSAAS
      may play a role in Alzheimer's disease pathology.

PMID- 24102335
TI  - Multiple sclerosis and cancer: when two wrongs make a right?
AB  - INTRODUCTION: Current treatments for multiple sclerosis (MS) remain partially
      successful, with certain patients remaining treatment resistant. A recent
      treatment, known as 'immunoablation' has been used in severe cases of adult MS
      with promising results. However, due to its high risk and reservation for severe
      or refractory cases, its full potential remains unknown. METHODS: We report the
      case of MM, a 14-year-old boy diagnosed with MS and a concurrent diagnosis of
      Hodgkin's lymphoma. RESULTS: After receiving aggressive chemotherapy
      (immunoablation) for Hodgkin's lymphoma, MM's MS symptoms appear to have
      remitted, and he has remained progression- and disease activity-free for over six
      years. DISCUSSION: This case study will focus on MM's cognitive and behavioural
      development over this time, but will also discuss treatment implications raised
      by this rare case.

PMID- 24102336
TI  - Palladium-catalyzed C(sp2 and sp3)-H activation/C-O bond formation: synthesis of
      benzoxaphosphole 1- and 2-oxides.
AB  - An efficient synthetic method of benzoxaphosphole 1- and 2-oxides is reported
      from phosphonic and phosphinic acids without prefunctionalization through a Pd
      catalyzed C(sp(2) and sp(3))-H activation/C-O bond formation under aerobic
      conditions. 

PMID- 24102337
TI  - Vitamin D deficiency during pregnancy: confronting the issues.

PMID- 24102338
TI  - Changes in primary metabolites and polyphenols in the peel of "Braeburn" apples
      (Malus domestica Borkh.) during advanced maturation.
AB  - During the two growing seasons the evolution of primary metabolites and wide
      range of polyphenols in the "Braeburn" apple peel during advanced maturation were
      investigated. During the five weeks sucrose significantly increased, whereas
      fructose and glucose fluctuated around the same level in one season and decreased
      in another. Regarding malic and citric acids, an expected decrease was recorded.
      The concentrations of hydroxycinnamic acids, dihydrochalcones, and flavanols
      remained quite constant or slightly decreased during advanced apple ripening. On
      the contrary an intensive accumulation of quercetin glycosides and anthocyanins
      took place during this period, starting with the onset of rapid formation
      approximately 3 weeks before the technological maturity of apples. Total phenolic
      content was relatively constant or slightly increased. The present results
      suggest that measures designed to improve the apple color and quality of
      "Braeburn" apples should be performed approximately 3-4 weeks before the expected
      technological maturity of apples. 

PMID- 24102339
TI  - Inactivation of koi-herpesvirus in water using bacteria isolated from carp
      intestines and carp habitats.
AB  - Since its first outbreak in Japan in 2003, koi-herpesvirus (KHV) remains a
      challenge to the carp Cyprinus carpio L. breeding industry. In this study,
      inactivation of KHV in water from carp habitats (carp habitat water) was
      investigated with the aim of developing a model for rapidly inactivating the
      pathogen in aquaculture effluent. Experiments with live fish showed that, in carp
      habitat water, KHV lost its infectivity within 3 days. Indications were that
      inactivation of KHV was caused by the antagonistic activity of bacteria (anti-KHV
      bacteria) in the water from carp habitats. Carp habitat water and the intestinal
      contents of carp were therefore screened for anti-KHV bacteria. Of 581 bacterial
      isolates, 23 showed anti-KHV activity. An effluent treatment model for the
      disinfection of KHV in aquaculture effluent water using anti-KHV bacteria was
      developed and evaluated. The model showed a decrease in cumulative mortality and
      in the number of KHV genome copies in kidney tissue of fish injected with treated
      effluent compared with a positive control. It is thought that anti-KHV bacteria
      isolated from the intestinal contents of carp and from carp habitat water can be
      used to control KHV outbreaks. 

PMID- 24102340
TI  - Review article: evidence-based dietary advice for patients with inflammatory
      bowel disease.
AB  - BACKGROUND: The therapeutic effect of enteral nutrition in Crohn's disease (CD)
      and the epidemiological associations between diet and inflammatory bowel disease
      (IBD) implicate diet in IBD causation. There is little evidence, however, to
      support specific dietary changes and patients often receive contradictory advice.
      AIM: To review the literature on the impacts of diet on IBD causation and
      activity to produce guidance based on 'best available evidence'. METHOD: Review
      of Medline, Embase and Cochrane databases from 1975 to 2012 using MeSH headings
      'crohn's disease' 'ulcerative colitis' 'enteral' 'diet' 'nutrition' 'fatty acid'
      and 'food additives'. RESULTS: Enteral nutrition with a formula-defined feed is
      effective treatment for CD, but approximately 50% of patients relapse within 6
      months of return to normal diet. There is no direct evidence of benefit from any
      other specific dietary modification in CD, but indirect evidence supports
      recommendation of a low intake of animal fat, insoluble fibre and processed fatty
      foods containing emulsifiers. Foods tolerated in sustained remission may not be
      tolerated following relapse. Some evidence supports vitamin D supplementation. In
      ulcerative colitis (UC), evidence is weaker, but high intakes of meat and
      margarine correlate with increased UC incidence and high meat intake also
      correlates with increased likelihood of relapse. CONCLUSIONS: There is little
      evidence from interventional studies to support specific dietary recommendations.
      Nevertheless, people with IBD deserve advice based on 'best available evidence'
      rather than no advice at all, although dietary intake should not be
      inappropriately restrictive. Further interventional studies of dietary
      manipulation are urgently required.

PMID- 24102341
TI  - Preface: forum on frontiers and challenges in biomaterials.

PMID- 24102342
TI  - In vitro cytotoxicity of antimicrobial conjugated electrolytes: interactions with
      mammalian cells.
AB  - An estimated 19 000 deaths and $3-4 billion in health care costs per year in the
      United States are attributed to methicillin-resistant Staphlococcus aureus (MRSA)
      infections. Certain conjugated phenylene ethynylene (CPE)-based polymers (PPE)
      and oligomers (OPE) have been demonstrated to exhibit dark and light-activated
      antimicrobial activity. Until recently, the relative cytotoxicity of these PPEs
      and OPEs toward mammalian cells haas been unknown, limiting the applications for
      which they may be used (e.g., reducing and/or preventing the spread of
      untreatable bacterial strains). In this work, we examine the toxicity of CPEs to
      mammalian cells using cytotoxicity assays of cellular monolayers. Eight CPEs, two
      PPEs and six OPEs, were selected for these studies based on their biocidal
      activity, and diversity of repeat unit number and functional groups. Briefly, two
      cell types were exposed to CPEs at concentrations ranging from 1-100 ug/mL for 24
      h. We find that concentration largely determines the resulting viability of
      cells, although at intermediate concentrations (5-10 ug/mL), the effect of light
      on light-activated compounds is very important. Furthermore, we find that the
      longer-chained compounds are cytotoxic at much higher concentrations, and
      therefore have the widest range of concentrations available for potential
      applications. 

PMID- 24102343
TI  - Mean platelet volume is increased in patients with hypertensive crises.
AB  - Platelets may be activated in hypertension (HT). Hypertensive crisis is an
      extreme phenotype of HT and HT-related thrombotic complications. We aimed to
      assess mean platelet volume (MPV) in patients with hypertensive crises. This
      study included 215 hypertensive urgency (HU) patients (84 male, mean age = 66 +/-
      15 years) and 60 hypertensive emergency (HE) patients (26 male, mean age = 68 +/-
      13 years), who were admitted to the emergency department with a diagnosis of
      hypertensive crises. Control group was composed of age- and sex-matched 39
      normotensive patients. Blood samples were withdrawn for whole blood count and
      routine biochemical tests. Systolic blood pressure (BP) was significantly higher
      in the HE group than in the HU group (p < 0.001). Median mean platelet volume
      (MPV) was higher in the HE group compared with HU and control groups [9.5
      (Interquartile range, IQR: 8.7-10.1), 8.4 (IQR: 7.7-9.1), and 8.3 (IQR: 7.7-8.7)
      fl, each p < 0.001, respectively). In linear regression analysis, systolic BP
      (beta = 0.18, 95% confidence intervals (CI): 0.002-0.015, p = 0.007) and diabetes
      mellitus (beta = 0.24, 95% CI: 0.28-0.95, p < 0.001) were independently
      associated with MPV levels. Our findings show that MPV can be elevated in
      patients with HE and HU. It can be independently associated with systolic BP and
      diabetes mellitus. These findings imply that platelet activation contribute to
      the pathogenesis of thrombotic complications in hypertensive crises.

PMID- 24102344
TI  - Effects of iloprost on pain-free walking distance and clinical outcome in
      patients with severe stage IIb peripheral arterial disease: the FADOI 2bPILOT
      Study.
AB  - BACKGROUND: Patients with peripheral arterial disease (PAD) at stage IIb, pain
      free walking distance (PFWD) less than 100 m and unsuitable for revascularization
      have both impaired quality of life and severe clinical outcome. Aim of the study
      was to evaluate the efficacy of the prostacyclin analogue iloprost, added to
      standard therapy, in these patients. MATERIAL AND METHODS: Patients were
      randomized to receive standard medical therapy (Group A) or standard therapy plus
      iloprost (Group B), for 1 year. Iloprost was administered for 10 days every 3
      months. Treadmill test was performed every 3 months, in Group B before starting
      the 10-day iloprost cycle. RESULTS: Fifty patients in Group A and 51 in Group B
      were enrolled. Mean baseline and 12-month PFWD values were 75.4 +/- 21.3 and
      128.9 +/- 62.9 for iloprost group and 70.3 +/- 21.6 and 99.6 +/- 62.6 m for
      controls. Patients treated with iloprost had significantly higher PFWD at 9 and
      12 months. This finding was confirmed after carrying forward the last valid
      observation (124.7 +/- 63.4 vs. 88.4 +/- 63.1 m, P < 0.01). Major cardiovascular
      events occurred in 32.0% and 3.9% of patients in Group A and Group B,
      respectively (P < 0.001). Five patients in Group A died vs. none in Group B (P =
      0.02). No serious unexpected adverse reactions occurred in patients receiving
      iloprost. CONCLUSIONS: Iloprost, added to standard therapy, significantly
      increases exercise capacity in patients with PAD at severe stage IIb. The
      percentage of patients who died or experienced major cardiovascular events was
      significantly lower in patients receiving iloprost. Future studies should focus
      on the effects of this therapy on clinical outcome.

PMID- 24102346
TI  - The need for (cost)-effective interventions to enhance adherence with
      osteoporosis medications.

PMID- 24102348
TI  - Oral liarozole in the treatment of patients with moderate/severe lamellar
      ichthyosis: results of a randomized, double-blind, multinational, placebo
      controlled phase II/III trial.
AB  - BACKGROUND: Oral liarozole, a retinoic acid metabolism-blocking agent, may be an
      alternative to systemic retinoid therapy in patients with lamellar ichthyosis.
      OBJECTIVE: To demonstrate the efficacy and safety of once-daily oral liarozole in
      the treatment of moderate/severe lamellar ichthyosis. METHODS: This was a double
      blind, multinational, parallel phase II/III trial (NCT00282724). Patients aged >=
      14 years with moderate/severe lamellar ichthyosis [Investigator's Global
      Assessment (IGA) score >= 3] were randomized 3 : 3 : 1 to receive oral liarozole
      (75 or 150 mg) or placebo once daily for 12 weeks. Assessments included: IGA; a
      five-point scale for erythema, scaling and pruritus severity; Short Form-36
      health survey; Dermatology Life Quality Index (DLQI); and safety parameters. The
      primary efficacy variable was response rate at week 12 (responder: >= 2-point
      decrease in IGA from baseline). RESULTS: Sixty-four patients were enrolled. At
      week 12, 11/27 (41%; liarozole 75 mg), 14/28 (50%; liarozole 150 mg) and one out
      of nine (11%; placebo) patients were responders; the difference between groups
      (liarozole 150 mg vs. placebo) was not significant (P = 0.056). Mean IGA and
      scaling scores decreased from baseline in both liarozole groups at weeks 8 and 12
      vs. placebo; erythema and pruritus scores were similar between treatment groups.
      Improvement in DLQI score was observed in both liarozole groups. Treatment with
      liarozole for 12 weeks was well tolerated. CONCLUSIONS: The primary efficacy
      variable did not reach statistical significance, possibly owing to the small
      sample size following premature termination. However, once-daily oral liarozole,
      75 and 150 mg, improved scaling and DLQI and was well tolerated in patients with
      moderate/severe lamellar ichthyosis.

PMID- 24102347
TI  - High-fat diet promotes lung fibrosis and attenuates airway eosinophilia after
      exposure to cockroach allergen in mice.
AB  - Obesity is an important risk factor for asthma but the mechanistic basis for this
      association is not well understood. In the current study, the impact of obesity
      on lung inflammatory responses after allergen exposure was investigated. C57BL/6
      mice maintained on a high-fat diet (HFD) or a normal diet (ND) after weaning were
      sensitized and challenged with cockroach allergen (CRA). Airway inflammation was
      assessed based on inflammatory cell recruitment, measurement of lung Th1-Th2
      cytokines, chemokines, eicosanoids, and other proinflammatory mediators as well
      as airway hyperresponsiveness (AHR). CRA-challenged mice fed a HFD exhibited
      significantly decreased allergen-induced airway eosinophilia along with reduced
      lung IL-5, IL-13, LTC4, CCL11, and CCL2 levels as well as reduced mucus secretion
      and smooth muscle mass compared to ND fed mice. However, allergen-challenged HFD
      fed mice demonstrated significantly increased PAI-1 and reduced PGE2 levels in
      the lung relative to corresponding ND fed mice. Interestingly, saline-exposed HFD
      fed mice demonstrated elevated baseline levels of TGF-beta1, arginase-1, hypoxia
      inducible factor-1alpha, and lung collagen expression associated with decreased
      lung function compared to corresponding ND fed mice. These studies indicate that
      a HFD inhibits airway eosinophilia while altering levels of PAI-1 and PGE2 in
      response to CRA in mice. Further, a HFD can lead to the development of lung
      fibrosis even in the absence of allergen exposure which could be due to innate
      elevated levels of specific profibrotic factors, potentially affecting lung
      function during asthma.

PMID- 24102350
TI  - Efficiency of intramolecular charge separation from the second excited state:
      suppression of the hot charge recombination by electron transfer to the secondary
      acceptor.
AB  - Ultrafast intramolecular charge transfer induced by the Soret-band excitation of
      the donor-acceptor1-acceptor2 molecular triads has been explored within the
      stochastic point-transition model. It is shown that nonthermal (hot) charge
      transfer from the primary to the secondary acceptor, assisted by relaxation of
      solvent polarization, can effectively screen ultrafast back electron transfer
      into the first excited state of the donor. Ways to increase the quantum yield of
      the charge-separated states are discussed. The dependencies of the quantum yield
      of the charge-separated states on the main electron transfer parameters: the free
      energy gaps, the reorganization energy of the solvent and intramolecular
      vibrational modes, the electronic couplings, and the solvent relaxation timescale
      are revealed. The important role of the geometry of the donor-acceptor1-acceptor2
      triad in charge separation effectiveness is emphasized. For the zinc-porphyrin
      imide1-imide2 triad, the charge-transfer parameters maximizing the quantum yield
      of the charge separated states are estimated. 

PMID- 24102349
TI  - Relationship between daily mood and migraine in children.
AB  - BACKGROUND: Retrospective and cross-sectional studies have suggested a
      bidirectional relationship between migraine and mood disturbance. OBJECTIVE: The
      present prospective daily diary study examined the prevalence and temporal
      associations between migraine and daily mood, mood and next-day headache, and
      headache and next-day mood. METHODS: Sixty-nine children (50 females, 19 males)
      between the ages of 7 and 12 years and their parents attending neurology clinic
      appointments and having a diagnosis of migraine as defined by International
      Headache Classification 2nd edition criteria completed measures on the quality of
      life, headache disability, child emotions, and child behaviors. Children and
      parents then recorded children's headache occurrence, headache duration, headache
      severity, mood, daily hassles, and medication use on paper diaries once a day for
      2 consecutive weeks. "Mood" was defined using the Facial Affective Scale, which
      is a visual representation of negative and positive affect. Data were analyzed
      using multilevel models. RESULTS: Controlling for age, sex, quality of life,
      headache disability, and medication use, worse mood was associated with same-day
      occurrence, longer duration, and more severe headache in both child and parent
      report. Today's mood was not consistently associated with next-day headache, and
      today's headache was not associated with next-day mood in either child or parent
      report. CONCLUSIONS: Results of this study lend support to a complex relationship
      between mood and headache in children with migraine. More research is needed to
      further elucidate the temporal nature of this relationship within a given day and
      over an extended period of time.

PMID- 24102352
TI  - Magnetic resonance imaging of fetal heart: anatomical and pathological findings.
AB  - Congenital heart disease is one of the most frequent prenatal malformation
      representing an incidence of 5/1000 live births; moreover, it represents the
      first cause of death in the first year of life. There is a wide range of severity
      in congenital heart malformations from lesions which require no treatment such as
      small ventricular septal defects, to lesions which can only be treated with
      palliative surgery such as hypoplastic left heart syndrome. A good prenatal
      examination acquires great importance in order to formulate an early diagnosis
      and improve pregnancy management. Nowadays, echocardiography still represents the
      gold standard examination for fetal heart disease. However, especially when
      preliminary ultrasound is inconclusive, fetal MRI is considered as a third-level
      imaging modality. Preliminary experiences have demonstrated the validity of this
      reporting a diagnostic accuracy of 79%. Our article aims to outline feasibility
      of fetal MRI in the anatomic evaluation, the common indication to fetal MRI, its
      role in the characterization of congenital heart defects, and at last its main
      limitations.

PMID- 24102351
TI  - Indirect effects drive evolutionary responses to global change.
AB  - Anthropogenic environmental changes pose significant threats to plant and animal
      populations. These changes also may affect the evolution of natural populations
      either directly or indirectly by altering the outcome of species interactions
      that are important drivers of evolution. This latter indirect pathway may be
      especially important for evolutionary responses to elevated atmospheric CO2
      concentrations (eCO2), which appear to have minimal direct effects on plant
      evolution but have large effects on interspecific interactions, such as
      competition. We manipulated competitive and CO2 environments of experimental
      Arabidopsis thaliana populations to test whether eCO2 alters evolutionary
      trajectories indirectly by altering selection imposed by competitors. We found
      that interspecific competition increased selection on growth traits, reduced
      heritabilities, and altered genetic covariances between traits and that the
      magnitude of these effects depended upon the CO2 environment. Although eCO2 had
      minimal direct effects on evolutionary processes, eCO2 typically reduced the
      strength of selection imposed by competitors and, therefore, relaxed selection on
      plant traits when competitors were present. Our results indicate that global
      changes may affect plant evolution indirectly by altering competitive
      interactions and underscore the importance of conducting research in natural
      communities when attempting to predict population responses to global change.

PMID- 24102345
TI  - The hypocretins/orexins: integrators of multiple physiological functions.
AB  - The hypocretins (Hcrts), also known as orexins, are two peptides derived from a
      single precursor produced in the posterior lateral hypothalamus. Over the past
      decade, the orexin system has been associated with numerous physiological
      functions, including sleep/arousal, energy homeostasis, endocrine, visceral
      functions and pathological states, such as narcolepsy and drug abuse. Here, we
      review the discovery of Hcrt/orexins and their receptors and propose a hypothesis
      as to how the orexin system orchestrates these multifaceted physiological
      functions.

PMID- 24102353
TI  - Supporting communication for children with cerebral palsy in hospital: views of
      community and hospital staff.
AB  - OBJECTIVE: We aimed to investigate the views of allied health and nursing staff
      on supporting the communication of children with cerebral palsy (CP) and complex
      communication needs (CCN) in hospital. METHOD: We conducted 12 focus groups with
      49 community- and hospital-based allied health professionals and hospital nurses.
      RESULTS: Participants reported having active roles in supporting children's
      seating, mobility, equipment, mealtime management and psychosocial needs, but not
      in supporting the children's communication in hospital. Participants described
      several environmental barriers to supporting children's augmentative and
      alternative communication (AAC) in hospital, and suggested a range of strategies
      to ease communication difficulties at the bedside. CONCLUSION: Results indicate a
      potential new role for community- and hospital-based health professionals in
      supporting nurses to implement AAC strategies at the bedside. Supporting nursing
      staff to remove environmental barriers and use communication technologies might
      create a more communicatively accessible hospital ward for children with CP and
      CCN.

PMID- 24102354
TI  - Detection of a novel betadelta-globin fusion gene, anti-lepore Hb CHORI
      (beta(through IVS-I-57)/delta(from IVS-I-101)), by multiplex ligation-dependent
      probe amplification.
AB  - Anti-Lepore hemoglobins (Hbs) are rare betadelta fusion variants that arise from
      non homologous crossover during meiosis. Using multiplex ligation-dependent probe
      amplification (MLPA), we identified a novel anti-Lepore Hb in an individual with
      an ambiguous Hb variant detected on routine screening by electrophoresis and high
      performance liquid chromatography (HPLC). The results of MLPA revealed
      duplication of beta and delta gene segments. Resolution of the rearrangement by
      DNA sequencing confirmed a novel anti-Lepore Hb, molecularly distinct from Hb P
      Nilotic, which we have named anti-Lepore Hb CHORI (Children's Hospital Oakland
      Research Institute) (beta(through IVS-I-57)/delta(from IVS-I-101)).

PMID- 24102355
TI  - Dynamin-2 in nervous system disorders.
AB  - Dynamin-2 is a pleiotropic GTPase whose best-known function is related to
      membrane scission during vesicle budding from the plasma or Golgi membranes. In
      the nervous system, dynamin-2 participates in synaptic vesicle recycling, post
      synaptic receptor internalization, neurosecretion, and neuronal process
      extension. Some of these functions are shared with the other two dynamin
      isoforms. However, the involvement of dynamin-2 in neurological illnesses points
      to a critical function of this isoform in the nervous system. In this regard,
      mutations in the dynamin-2 gene results in two congenital neuromuscular
      disorders. One of them, Charcot-Marie-Tooth disease, affects myelination and
      peripheral nerve conduction, whereas the other, Centronuclear Myopathy, is
      characterized by a progressive and generalized atrophy of skeletal muscles, yet
      it is also associated with abnormalities in the nervous system. Furthermore,
      single nucleotide polymorphisms located in the dynamin-2 gene have been
      associated with sporadic Alzheimer's disease. In the present review, we discuss
      the pathogenic mechanisms implicated in these neurological disorders.

PMID- 24102356
TI  - Practitioner review: schizophrenia spectrum disorders and the at-risk mental
      state for psychosis in children and adolescents--evidence-based management
      approaches.
AB  - BACKGROUND: Schizophrenia spectrum disorders are severe mental illnesses which
      often result in significant distress and disability. Attempts have been made to
      prospectively identify and treat young people viewed as at high risk of impending
      nonaffective psychosis. Once a schizophrenia spectrum disorder has developed,
      prompt identification and management is required. METHODS: This article reviews
      the literature relating to the assessment and management of 'at-risk mental
      states' (ARMS) and the treatment of schizophrenia spectrum disorders in children
      and adolescents. A systematic search of the literature was undertaken using
      EMBASE, MEDLINE, PsycINFO databases for the period January 1970-December 2012.
      RESULTS: Evidence suggests that young people fulfilling the ARMS criteria are at
      high risk of adverse mental health outcomes but that the majority do not develop
      nonaffective psychosis over the medium term. Although clinical trial findings
      have been inconsistent, psychosocial approaches, such as cognitive behaviour
      therapy, may reduce the risk of transition to psychosis and improve some
      symptoms, at least over the short term. The effectiveness of psychotropic
      medication for the ARMS is uncertain although there is accumulating evidence for
      potential adverse effects of antipsychotic medication, even at low dose, in this
      population. For the schizophrenias, clinical trial findings suggest that, as in
      adults, antipsychotics should be selected on the basis of side-effect profile
      although clozapine may be helpful in treatment refractory illness. There are
      almost no studies of psychosocial treatments for schizophrenia in young people
      under 18, and some caution must be exercised when extrapolating the findings of
      adult studies to younger individuals. CONCLUSIONS: A stepped care approach to the
      ARMS in young people represents a plausible potential management approach for
      those at high risk of serious mental health problems. However, predictive models
      currently lack precision and should focus on accurately identifying those at high
      risk for a variety of poor outcomes who may benefit most from intervention. There
      is also an urgent need for age-specific research in the area of psychosocial
      treatments for children and adolescents with schizophrenia.

PMID- 24102357
TI  - Primary anticoagulation with bivalirudin for patients with implantable
      ventricular assist devices.
AB  - Bivalirudin is a direct thrombin inhibitor that is increasingly used in patients
      undergoing mechanical circulatory support as it presents many advantages compared
      with unfractionated heparin. The aim of this study was to describe our experience
      with bivalirudin as primary anticoagulant in patients undergoing ventricular
      assist device (VAD) implantation. An observational study was performed on 12
      consecutive patients undergoing VAD implantation at our institution. Patients
      received a continuous infusion of bivalirudin, with a starting dose of 0.025
      mg/kg/h; the target activated partial thromboplastin time (aPTT) was between 45
      and 60 s. Patients never received heparin during hospitalization nor had a prior
      diagnosis of heparin-induced thrombocytopenia (HIT). All patients received a
      continuous flow pump except one. Preoperative platelets count was 134 000 +/- 64
      000 platelets/mm(3) . Mean bivalirudin dose was 0.040 +/- 0.026 mg/kg/h over the
      course of therapy (5-12 days). Lowest platelets count during treatment was 73 000
      +/- 23 000 platelets/mm(3) . No thromboembolic complications occurred. Two
      episodes of minor bleeding from chest tubes that subsided after reduction or
      temporary suspension of bivalirudin infusion were observed. Intensive care unit
      stay was 8 (7-17) days, and hospital stay was 25 (21-33) days. Bivalirudin is a
      valuable option for anticoagulation in patients with a VAD and can be easily
      monitored with aPTT. The use of a bivalirudin-based anticoagulation strategy in
      the early postoperative period may overcome many limitations of heparin and,
      above all, the risk of HIT, which is higher in patients undergoing VAD
      implantation. Bivalirudin should no longer be regarded as a second-line therapy
      for anticoagulation in patients with VAD. [Correction added on 6 December 2013,
      after first online publication: The dose of bivalirudin in the Abstract to 0.025
      mg/kg/h]. 

PMID- 24102360
TI  - Absence of effect of SLC22A2 genotype on cisplatin-induced nephrotoxicity in
      oesophageal cancer patients receiving cisplatin and 5-fluorouracil: report of
      results discordant with those of earlier studies.
AB  - WHAT IS KNOWN AND OBJECTIVE: Cancer patients treated with cisplatin chemotherapy
      frequently experience drug-induced nephrotoxicity. Clinical studies using a
      single chemotherapeutic regimen or large sample sizes for patients with the
      SLC22A2 808T allele have not been reported. Here, we examined 95 patients with
      oesophageal cancer who received 5-fluorouracil and cisplatin (FP) to determine
      whether nephrotoxicity was affected by SLC22A2 808G>T polymorphism. METHODS: The
      change rate of the estimated glomerular filtration rate (eGFR) was used for the
      evaluation of cisplatin-induced nephrotoxicity and calculated for each patient
      according to the following formula: change rate = (prechemotherapy value - post
      chemotherapy value)/prechemotherapy value. Genotyping of SLC22A2 808G>T was
      carried out using the polymerase chain reaction-restriction fragment length
      polymorphism (PCR-RFLP) method. RESULTS: The eGFR after FP chemotherapy was
      significantly lower than that before chemotherapy, and the mean difference in
      eGFR was 25.7 mL/min (P < 0.01). There was no significant difference in the mean
      change rate of the eGFR following FP chemotherapy between the SLC22A2 808GG
      genotype (n = 70) and the 808GT+TT genotypes (n = 25) (27.9% and 27.8%,
      respectively). In multiple regression analyses, the change rate of eGFR following
      FP chemotherapy was associated with the eGFR value prior to chemotherapy (P =
      0.04). WHAT IS NEW AND CONCLUSION: In FP chemotherapy for oesophageal cancers,
      cisplatin-induced nephrotoxicity seems to be unaffected by the SLC22A2 808G>T
      polymorphism. The eGFR prior to chemotherapy might be an important risk factor
      for cisplatin-induced nephrotoxicity. Our present study was estimated with a
      single chemotherapeutic regimen, eGFR, and was calculated using serum creatinine,
      age and the sex of the patient and sample sizes of 25 patients with SLC22A2 808T
      allele. However, further examinations with a larger sample size to corroborate
      the study results might be necessary.

PMID- 24102361
TI  - Diagnoses of gastrointestinal cancers after gastrointestinal bleeding in patients
      receiving clopidogrel or warfarin.
AB  - BACKGROUND AND AIMS: The association between gastrointestinal (GI) bleeding and
      subsequent detection of GI cancer in patients using antiplatelet/anticoagulant
      medications is unclear. We investigated the association between the occurrence of
      GI bleeding and the detection of GI cancer and assessed whether this association
      differs in patients treated with clopidogrel or warfarin compared to non-treated
      patients. METHODS: A claims analysis was conducted using the Truven Health
      MarketScan((r)) Research databases. Patients were grouped into the treatment
      cohort if they received a prescription for clopidogrel or warfarin or into the
      non-treatment cohort if they did not receive these medications. Hazard ratios
      (HRs) and 95% confidence intervals (CIs) were calculated for GI cancer diagnosed
      after GI bleeding. RESULTS: Overall, in the treatment cohort, patients who
      experienced a GI bleed were 6 times (HR: 5.64, 95% CI, 5.12, 6.21) more likely to
      be diagnosed with GI cancer compared with those without bleeding. In the non
      treatment cohort patients were 13 times (HR: 13.34, 95% CI, 12.21, 14.58) more
      likely to be diagnosed with GI cancer after GI bleeding. The HRs of GI cancer
      were higher within 6 months of the first GI bleed and decreased remarkably
      thereafter. CONCLUSIONS: This study suggests that an episode of GI bleeding
      increased the rates of detection of GI cancers.

PMID- 24102362
TI  - Recurrent gastrointestinal bleeding in a patient with Eisenmenger syndrome using
      bosentan.
AB  - Eisenmenger syndrome is associated with irreversible increase in pulmonary
      vascular resistance causing reduced survival. Bosentan, a non-selective
      endothelin receptor antagonist is the commonly used specific pulmonary arterial
      hypertension drug in Eisenmenger syndrome. In this paper, we present a case of
      recurrent gastrointestinal bleeding in a 23-year-old female with Eisenmenger
      syndrome who was only under bosentan treatment, which has not been reported
      previously. Most common adverse effect of bosentan is elevation in the liver
      enzymes however, bleeding complication is very rare. On the contrary, it was
      proposed that bosentan might be a potential protector against hyperacidity and
      mucosal erosion that occur as a consequence of stress. Although the mechanistic
      relationship of bleeding tendency and role of Eisenmenger syndrome concomitant
      with bosentan treatment is far from conclusive statement for now, this
      association warrants and should draw attention of clinicians and researches in
      this field. 

PMID- 24102363
TI  - Reactive oxygen species modulate the differential expression of methionine
      sulfoxide reductase genes in Chlamydomonas reinhardtii under high light
      illumination.
AB  - Illumination of Chlamydomonas reinhardtii cells at 1000 (high light, HL) or 3000
      (very high light, VHL) umol photons m(-2)  s(-1) intensity increased superoxide
      anion radical (O(2)(*-)) and hydrogen peroxide (H(2)O(2)) production, and VHL
      illumination also increased the singlet oxygen ((1)O(2)) level. HL and VHL
      illumination decreased methionine sulfoxide reductase A4 (CrMSRA4) transcript
      levels but increased CrMSRA3, CrMSRA5 and CrMSRB2.1 transcripts levels. CrMSRB2.2
      transcript levels increased only under VHL conditions. The role of reactive
      oxygen species (ROS) on CrMSR expression was studied using ROS scavengers and
      generators. Treatment with dimethylthiourea (DMTU), a H(2)O(2) scavenger,
      suppressed HL- and VHL-induced CrMSRA3, CrMSRA5 and CrMSRB2.1 expression, whereas
      H(2)O(2) treatment stimulated the expression of these genes under 50 umol photons
      m(-2)  s(-1) conditions (low light, LL). Treatment with diphenylamine (DPA), a
      (1)O(2) quencher, reduced VHL-induced CrMSRA3, CrMSRA5 and CrMSRB2.2 expression
      and deuterium oxide, which delays (1)O(2) decay, enhanced these gene expression,
      whereas treatment with (1)O(2) (rose bengal, methylene blue and neutral red) or
      O(2)(*-) (menadione and methyl viologen) generators under LL conditions induced
      their expression. DPA treatment inhibited the VHL-induced decrease in CrMSRA4
      expression, but other ROS scavengers and ROS generators did not affect its
      expression under LL or HL conditions. These results demonstrate that the
      differential expression of CrMSRs under HL illumination can be attributed to
      different types of ROS. H(2)O(2), O(2) (*-) and (1)O(2) modulate CrMSRA3 and
      CrMSRA5 expression, whereas H(2)O(2) and O(2)(*-) regulate CrMSRB2.1 and
      CrMSRB2.2 expression, respectively. (1)O(2) mediates the decrease of CrMSRA4
      expression by VHL illumination, but ROS do not modulate its decrease under HL
      conditions.

PMID- 24102364
TI  - B-type natriuretic peptide and severity of cognitive disorder.
AB  - BACKGROUND: Natriuretic peptides have been linked to cognitive disorder in
      previous studies. The aim of this study was to examine the association between
      the severity of cognitive disorder and the levels of B-type natriuretic peptide
      (BNP) in an older general population. MATERIAL AND METHODS: This study is a part
      of the larger population-based, multidisciplinary Kuopio 75+ health study. A
      total of 601 subjects aged 75 or older participated in the study. A subgroup of
      126 individuals was diagnosed with cognitive disorder, and the severity of the
      disease was assessed. The participants were tested for BNP. Analysis of
      covariance was carried out to study the relationship between BNP and the stage of
      cognitive disorder. RESULTS: The association between the level of cognitive
      disorder and BNP resembled an inverse U-shaped curve, with higher levels of BNP
      observed among participants with mild cognitive disorder when compared to
      cognitively intact participants or counterparts with more severe cognitive
      disorder. This effect remained after adjustment for age (P = 0.02). However,
      association between BNP and level of cognitive disorder was lost in further
      adjustment with covariates connected to the levels of BNP. CONCLUSION: The
      previously reported elevation of natriuretic peptides among individuals with
      diagnosed cognitive disorder was found only in people with milder stages of the
      disorder.

PMID- 24102365
TI  - Moderate-severe traumatic brain injury causes delayed loss of white matter
      integrity: evidence of fornix deterioration in the chronic stage of injury.
AB  - OBJECTIVES: To examine structural integrity loss in the fornix from 5-30 months
      after moderate and severe traumatic brain injury (TBI) using diffusion tensor
      imaging. METHODS: MRIs were prospectively undertaken in 29 adults with moderate
      and severe TBI at two time points. Fractional anisotropy (FA) was calculated for
      the fornix (column/body, right crux and left crux) at 5 and 30 months post
      injury. RESULTS: Paired t-tests revealed significant FA reductions with large
      effect sizes across time in the column/body, p < 0.001, right crux, p < 0.001 and
      left crux, p < 0.001. CONCLUSIONS: These data contribute to the growing body of
      evidence that loss of white matter continues in moderate and severe TBI even
      after the acute neurological effects of TBI have resolved. As the fornix plays a
      critical role in memory, this may be a contributing factor to the poor clinical
      outcomes observed in these patients.

PMID- 24102366
TI  - Impaired induction of allergic lung inflammation by Alternaria alternata mutant
      MAPK homologue Fus3.
AB  - The fungal allergen Alternaria alternata is associated with development of
      asthma, though the mechanisms underlying the allergenicity of Alternaria are
      largely unknown. The aim of this study was to identify whether the MAP kinase
      homologue Fus3 of Alternaria contributed to allergic airway responses. Wild-type
      (WT) and Fus3 deficient Alternaria extracts were given intranasal to mice.
      Extracts from Fus3 deficient Alternaria that had a functional copy of Fus3
      introduced were also administered (CpFus3). Mice were challenged once and levels
      of BAL eosinophils and innate cytokines IL-33, thymic stromal lymphopoeitin
      (TSLP), and IL-25 (IL-17E) were assessed. Alternaria extracts or protease
      inhibited extract were administered with (OVA) during sensitization prior to
      ovalbumin only challenges to determine extract adjuvant activity. Levels of BAL
      inflammatory cells, Th2 cytokines, and OX40-expressing Th2 cells as well as
      airway infiltration and mucus production were measured. WT Alternaria induced
      innate airway eosinophilia within 3 days. Mice given Fus3 deficient Alternaria
      were significantly impaired in developing airway eosinophilia that was largely
      restored by CpFus3. Further, BAL IL-33, TSLP, and Eotaxin-1 levels were reduced
      after challenge with Fus3 mutant extract compared with WT and CpFus3 extracts. WT
      and CpFus3 extracts demonstrated strong adjuvant activity in vivo as levels of
      BAL eosinophils, Th2 cytokines, and OX40-expressing Th2 cells as well as
      peribronchial inflammation and mucus production were induced. In contrast, the
      adjuvant activity of Fus3 extract or protease-inhibited WT extract was largely
      impaired. Finally, protease activity and Alt a1 levels were reduced in Fus3
      mutant extract. Thus, Fus3 contributes to the Th2-sensitizing properties of
      Alternaria.

PMID- 24102368
TI  - Voltammetric determination of the reversible potentials for
      [{Ru4O4(OH)2(H2O)4}(gamma-SiW10O36)2]10- over the pH range of 2-12: electrolyte
      dependence and implications for water oxidation catalysis.
AB  - Voltammetric studies of the Ru-containing polyoxometalate water oxidation
      molecular catalyst [{Ru4O4(OH)2(H2O)4}(gamma-SiW10O36)2](10-) ([1(gamma
      SiW10O36)2](10-) where 1 represents the {Ru4O4(OH)2(H2O)4} core and 1(0) stands
      for its initial form with all ruthenium centers in the oxidation state IV) have
      been carried out in aqueous media over a wide range of pH (2-12 using Britton
      Robinson buffer) and ionic strength. Well-defined voltammograms in buffered media
      are only obtained when Frumkin double layer effects are suppressed by the
      presence of a sufficient concentration of additional supporting electrolyte
      (LiNO3, NaNO3, KNO3, Ca(NO3)2, Mg(NO3)2, MgSO4, or Na2SO4). A combination of data
      derived from dc cyclic, rotating disk electrode, and Fourier transformed large
      amplitude ac voltammetry allow the assignment of two processes related to
      reduction of the framework and the complete series of Ru(III/IV) and Ru(IV/V)
      redox processes and also provide their reversible potentials. Analysis of these
      data reveals that K(+) has a significantly stronger interaction with 1(1) (the
      number inside bracket stands for the number of electrons removed from 1(0)) than
      found for the other cations investigated, and hence its presence significantly
      alters the pH dependence of the 1(0)/1(1) reversible potential. Comparison of
      experimental data with theory developed in terms of equilibrium constants for
      process 1(0)/1(1) reveals that both H(+) and K(+) interact competitively with
      both 1(0) and 1(1). Importantly, reversible potential data reveal that (i) proton
      transfer does not necessarily need to be coupled to all electron transfer steps
      to achieve catalytic oxidation of water, (ii) the four-electron oxidized form,
      1(4), is capable of oxidizing water under all conditions studied, and (iii) under
      some conditions, the three-electron oxidized form, 1(3), also exhibits
      considerable catalytic activity. 

PMID- 24102367
TI  - Conformational preferences of zampanolide and dactylolide.
AB  - The solution conformation behavior of the macrolide core of microtubule
      stabilizing agents (-)-zampanolide and (-)-dactylolide has been determined
      through a combination of high-field NMR experiments and computational modeling.
      Taken together, the results demonstrate that in solution both molecules exist as
      a mixture of three interconverting conformational families, one of which bears
      strong resemblance to zampanolide's tubulin-bound conformation. 

PMID- 24102369
TI  - A randomized trial comparing methyl aminolaevulinate photodynamic therapy with
      and without Er:YAG ablative fractional laser treatment in Asian patients with
      lower extremity Bowen disease: results from a 12-month follow-up.
AB  - BACKGROUND: Methyl aminolaevulinate photodynamic therapy (MAL-PDT) is an
      effective treatment for Bowen disease (BD) of the lower extremities. Er:YAG
      (erbium:yttrium-aluminium-garnet) ablative fractional laser (AFL) treatment
      removes the stratum corneum to increase MAL uptake and may improve efficacy.
      However, no studies have directly compared the efficacy of MAL-PDT with and
      without Er:YAG AFL therapy in treating BD of the lower extremities in Asians.
      OBJECTIVES: To compare the efficacy, recurrence rate, cosmetic outcomes and
      safety between Er:YAG AFL-assisted MAL-PDT (Er:YAG AFL-PDT) and standard MAL-PDT.
      METHODS: Twenty-one patients with a total of 58 BD lesions randomly received
      either one session of Er:YAG AFL-PDT or two sessions of MAL-PDT in two
      symmetrical areas. Er:YAG AFL therapy was performed with 550-600 MUm ablation
      depth, level 1 coagulation, 22% treatment density and a single pulse. MAL cream
      was then applied under occlusion for 3 h and illuminated with a red light
      emitting diode lamp at 37 J cm(-2) . A second session of MAL-PDT was administered
      7 days later. Overall response rate, recurrence rate, cosmetic outcomes and
      safety were assessed at 1 week, 3 and 12 months after treatment. RESULTS: After 3
      months, Er:YAG AFL-PDT was significantly more effective (93.8%) than MAL-PDT
      (73.1%; P = 0.031), and the recurrence rate was significantly lower for Er:YAG
      AFL-PDT (6.7%) than MAL-PDT (31.6%) at 12 months (P = 0.022). No significant
      difference was found between Er:YAG AFL-PDT and MAL-PDT in terms of cosmetic
      outcomes or safety. CONCLUSIONS: Er:YAG AFL-PDT showed significantly higher
      efficacy and lower recurrence rate than did standard MAL-PDT for treating lower
      extremity BD in an Asian population.

PMID- 24102370
TI  - Risk factors associated with myocardial infarction in venous thromboembolism
      patients.
AB  - BACKGROUND: Although risk factors for MI have been described in the general
      population, there is a lack of data on the assessment of risk factors associated
      with MI in venous thromboembolism (VTE) patients. OBJECTIVE: The purpose of this
      study was to identify risk factors associated with MI in VTE patients. PATIENTS
      AND METHODS: Health insurance claims between January 2004 and September 2008 from
      the Ingenix IMPACT database were analyzed. Patients aged >=18 years were
      identified as of the date of their first VTE diagnosis with >=1 year of
      continuous insurance coverage before the index VTE. The risk of MI for VTE
      patients with 1, 2, and >=3 major risk factors as identified by published
      guidelines was calculated. Multivariate Cox proportional hazard models were
      conducted to identify the most predictive risk factors associated with MI.
      RESULTS: A total of 177,885 VTE patients were identified; 4412 (2.5%) developed
      an MI during a mean follow-up period of 1.3 years. Previous MI, age (>=65 years),
      and coronary artery disease were the most predictive risk factors of MI with
      adjusted hazard ratios (HRs; 95% CI) of 5.47 (5.01-5.97), 1.78 (1.66-1.91), and
      1.60 (1.48-1.74), respectively. Adjusted HRs (95% CI) for VTE patients with 1, 2,
      and >=3 major risk factors relative to no major risk factor were 2.34 (1.94
      2.81), 3.21 (2.67-3.85), and 6.93 (5.85-8.22), respectively. LIMITATIONS: These
      included possible inaccuracies or omissions in diagnoses, classification bias
      such as the identification of false-positive MI events, and the likely
      undercoding of some risk factors such as social issues. CONCLUSIONS: Traditional
      major cardiovascular risk factors are also predictive of MI in VTE patients.
      Having multiple major risk factors significantly increases the probability of
      developing MI events in VTE patients.

PMID- 24102371
TI  - Combination of mean platelet volume and the GRACE risk score better predicts
      future cardiovascular events in patients with acute coronary syndrome.
AB  - Both the Global Registry of Acute Coronary Events (GRACE) risk score and mean
      platelet volume (MPV) can independently predict adverse cardiovascular disease
      (CVD) events in patients with acute coronary syndrome (ACS). This study was aimed
      at investigating whether MPV was related to the GRACE risk score and whether the
      combination of them could have a better performance in predicting CVD in Patients
      with ACS. Totally 297 ACS patients were included. MPV was measured on admission.
      The GRACE risk score was calculated and its predictive value alone and together
      with MPV was assessed, respectively. During a median period of 52 months (range,
      6 to 65), 11 of the 297 subjects (3.7%) were lost to follow-up, and 132 (46.2%)
      had adverse CVD including 32 deaths. Both MPV and the GRACE score were higher in
      patients with CVD events than those without events, and the GRACE score increased
      with the increase of MPV. Multivariate Cox analysis demonstrated that both MPV
      and the GRACE score were significant and independent predictors for CVD events
      (HR: 1.13; 95% CI: 1.10 to 1.15; p = 0.006; HR: 1.30; 95% CI: 1.24 to 1.37; p <
      0.001; respectively). The area under the ROC curve was 0.70 (95% CI: 0.64 to
      0.76, p < 0.001) when the GRACE score was calculated alone, whereas it increased
      to 0.85 (95% CI: 0.81 to 0.90, p < 0.001) with the addition of MPV, indicating
      that the combination of MPV with the scoring system improved the predictive
      value. This study demonstrates for the first time that MPV is positively
      associated with the GRACE risk score and it may complement the scoring system in
      predicting CVD events in patients with ACS.

PMID- 24102372
TI  - Assay of urinary excretion of polyphenols after ingestion of a cup of mountain
      tea (Sideritis scardica) measured by HPLC-DAD-ESI-MS/MS.
AB  - Flavonoids and phenolic acid metabolites excreted in human urine after ingestion
      of Sideritis scardica decoction with characterized polyphenolic composition were
      studied. A feeding study was carried out with 10 human volunteers, and urine
      samples were collected for 24 h after ingestion of the Sidertis decoction.
      Polyphenol metabolites were identified and quantified in urine samples by HPLC
      with tandem mass spectrometric detection. Thirty-one different metabolites of
      hypolaetin, methylhypolaetin, isoscutellarein, methylisoscutellarein, and
      apigenin and 32 phenolic acid metabolites were detected and quantified using a
      method validated for this purpose. The urinary excretion of polyphenol
      metabolites corresponded to 5% (n/n) of the intake of polyphenols from the
      Sideritis decoction. Flavonoid metabolites were dominant in urine samples with 87
      94% of total polyphenolic metabolites content. The most abundant metabolites were
      methylhypolaetin and methylisoscutellarein glucuronides. Urinary excretion of
      isoscutellarein (35.61%) was 10 times higher than that of hypolaetin (3.67%).
      Apigenin also showed high urinary excretion (32.46%). 

PMID- 24102373
TI  - Solvent effect on anthranilic acid spectroscopy.
AB  - The spectroscopy of anthranilic acid (AA) was examined in neat and binary
      solvents of varying polarity and hydrogen bonding strength in order to understand
      the role of water in solvating the polar sites of the molecule. With the
      exception of water, the Stokes shift of AA in different solvents was found to be
      linearly correlated with the normalized molar transition energy of solvent
      polarity (ETN), indicating the major role of the hydrogen bonding effect in
      solution. Analysis of the absorption and fluorescence spectra reveals that AA
      exists as an anion in neutral water. The pKa (4.50) and pKa* (4.44) values were
      estimated from the spectral shift in the absorption and fluorescence spectra
      measured in different pH solutions. The shortest fluorescence lifetime was
      measured in cyclohexane and is attributed to intramolecular hydrogen
      dislocation/transfer in the excited state. The lifetime values in polar solvents
      point to the dominant effect of the hydrogen-bond donating strength (alpha value)
      of the solvent. The number of water molecules solvating the polar region of the
      neutral form of AA was estimated to be three from the absorbance change in
      dioxane/buffer (pH 3.5) binary mixtures. The structures of AA:water complexes
      were calculated from density functional theory using the B3LYP method with a 6
      311++G(2d,p) basis set. A stepwise addition of water molecules (1-3) to the polar
      region of AA leads to a preferential solvation of the COOH group of the molecule
      in a closed-cyclic geometry. It is worth noting that the spectral shift as a
      function of pH suggests the suitability of AA as a probe to estimate the local
      acidity of binding sites in macromolecules in the pH range 3.0-7.0.

PMID- 24102374
TI  - Utilization of stem cells in alginate for nucleus pulposus tissue engineering.
AB  - In a general view of anatomy, intervertebral disc is composed of three parts:
      annulus fibrosus (AF), nucleus pulposus (NP), and cartilage endplate (CEP).
      Recently, several types of stem cells were successfully isolated from these
      corresponding regions, but up to now, no research was performed about which kind
      of stem cells is the most efficient candidate for NP tissue engineering or for
      stem cell-based disc regeneration therapy. In this study, we compared the
      regenerative potentials of the above-mentioned three kinds of disc-derived stem
      cells with that of the classic bone marrow (BM)-mesenchymal stem cells (MSCs) in
      a rabbit disc degeneration model. By magnetic resonance imaging (MRI), X-ray,
      histology, etc. evaluations, we found that cartilage endplate-derived stem cells
      (CESCs) showed superior capacity compared with the annulus fibrosus-derived stem
      cells (AFSCs), nucleus pulposus-derived stem cells (NPSCs), and BM-MSCs (p<0.05);
      additionally, when comparing the CESC group with the normal control group, there
      existed no statistical difference in X-ray (p>0.05). Those results demonstrated
      that the CESC-seeded alginate construct performed the most powerful ability for
      NP regeneration, while AFSCs showed the most inferior potency, NPSCs and BM-MSCs
      had similar regenerative capacity and located in the middle. All in all, our
      study showed that CESCs might act as an efficient seed cell source for NP tissue
      engineering, which paved a new way for the biological solution of disc
      degeneration diseases. 

PMID- 24102375
TI  - Trait-directed de novo population transcriptome dissects genetic regulation of a
      balanced polymorphism in phosphorus nutrition/arsenate tolerance in a wild grass,
      Holcus lanatus.
AB  - The aim of this study was to characterize the transcriptome of a balanced
      polymorphism, under the regulation of a single gene, for phosphate fertilizer
      responsiveness/arsenate tolerance in wild grass Holcus lanatus genotypes screened
      from the same habitat. De novo transcriptome sequencing, RNAseq (RNA sequencing)
      and single nucleotide polymorphism (SNP) calling were conducted on RNA extracted
      from H. lanatus. Roche 454 sequencing data were assembled into c. 22,000 isotigs,
      and paired-end Illumina reads for phosphorus-starved (P-) and phosphorus-treated
      (P+) genovars of tolerant (T) and nontolerant (N) phenotypes were mapped to this
      reference transcriptome. Heatmaps of the gene expression data showed strong
      clustering of each P+/P- treated genovar, as well as clustering by N/T phenotype.
      Statistical analysis identified 87 isotigs to be significantly differentially
      expressed between N and T phenotypes and 258 between P+ and P- treated plants.
      SNPs and transcript expression that systematically differed between N and T
      phenotypes had regulatory function, namely proteases, kinases and ribonuclear RNA
      binding protein and transposable elements. A single gene for arsenate tolerance
      led to distinct phenotype transcriptomes and SNP profiles, with large differences
      in upstream post-translational and post-transcriptional regulatory genes rather
      than in genes directly involved in P nutrition transport and metabolism per se.

PMID- 24102376
TI  - Headache diagnoses among Iraq and Afghanistan war veterans enrolled in VA: a
      gender comparison.
AB  - OBJECTIVE: To examine the prevalence and correlates of headache diagnoses, by
      gender, among Iraq and Afghanistan War Veterans who use Department of Veterans
      Affairs (VA) health care. BACKGROUND: Understanding the health care needs of
      recent Veterans, and how these needs differ between women and men, is a priority
      for the VA. The potential for a large burden of headache disorders among Veterans
      seeking VA services exists but has not been examined in a representative sample.
      METHODS: We conducted a historical cohort study using national VA inpatient and
      outpatient data from fiscal year 2011. Participants were all (n = 470,215) Iraq
      and Afghanistan War Veteran VA users in 2011; nearly 13% were women. We
      identified headache diagnoses using International Classification of Diseases (ICD
      9) diagnosis codes assigned during one or more VA inpatient or outpatient
      encounters. Descriptive analyses included frequencies of patient characteristics,
      prevalence and types of headache diagnoses, and prevalence of comorbid diagnoses.
      Prevalence ratios (PR) with 95% confidence intervals (CI) were used to estimate
      associations between gender and headache diagnoses. Multivariate models adjusted
      for age and race. Additional models also adjusted for comorbid diagnoses.
      RESULTS: In 2011, 56,300 (11.9%) Veterans received a headache-related diagnosis.
      While controlling for age and race, headache diagnoses were 1.61 times more
      prevalent (95% CI = 1.58-1.64) among women (18%) than men (11%). Most of this
      difference was associated with migraine diagnoses, which were 2.66 times more
      prevalent (95% CI = 2.59-2.73) among women. Cluster and post-traumatic headache
      diagnoses were less prevalent in women than in men. These patterns remained the
      same when also controlling for comorbid diagnoses, which were common among both
      women and men with headache diagnoses. The most prevalent comorbid diagnoses
      examined were depression (46% of women with headache diagnoses vs 40% of men),
      post-traumatic stress disorder (38% vs 58%), and back pain (38% vs 46%).
      CONCLUSIONS: Results of this study have implications for the delivery of post
      deployment health services to Iraq and Afghanistan War Veterans. Migraine and
      other headache diagnoses are common among Veterans, particularly women, and tend
      to occur in combination with other post-deployment health conditions for which
      patients are being treated.

PMID- 24102377
TI  - Mothers' prenatal stress and their children's antisocial outcomes--a moderating
      role for the dopamine D4 receptor (DRD4) gene.
AB  - BACKGROUND: Maternal distress during pregnancy has been linked to aggressive
      behavior in offspring. This effect has been interpreted in terms of 'fetal
      programming'. The 7-repeat (7r) allele of a VNTR polymorphism in exon III of the
      human dopamine receptor D4 (DRD4) has consistently been associated with
      externalizing behavior problems, especially in the presence of adverse
      environmental factors. So far, it is not known whether the DRD4 genotype
      moderates the effect of prenatal maternal stress on the development of childhood
      antisocial behavior. METHODS: As part of an ongoing epidemiological cohort study,
      prenatal maternal stress was assessed using self-report 3 months following child
      birth. When children were 8, 11, and 15 years old, mothers rated their children's
      externalizing behavior, and diagnoses of conduct disorder and/or oppositional
      defiant disorder (CD/ODD) according to DSM-IV were obtained. In a sample of N =
      308 participants, the effects of the DRD4 genotype, prenatal maternal stress, and
      the interaction thereof on antisocial outcome were tested. RESULTS: Under
      conditions of elevated prenatal maternal stress, children carrying one or two
      DRD4 7r alleles were at increased risk of a diagnosis of CD/ODD. Moreover,
      homozygous carriers of the DRD4 7r allele displayed more externalizing behavior
      following exposure to higher levels of prenatal maternal stress, while homozygous
      carriers of the DRD4 4r allele turned out to be insensitive to the effects of
      prenatal stress. CONCLUSIONS: This study is the first to report a gene
      environment interaction related to DRD4 and prenatal maternal stress using data
      from a prospective study, which extends earlier findings on the impact of
      prenatal maternal stress with respect to childhood antisocial behavior.

PMID- 24102378
TI  - Epigenetic activation of mouse ganglioside synthase genes: implications for
      neurogenesis.
AB  - The quantity and expression pattern of gangliosides in mammalian brain change
      drastically during development and are mainly regulated through stage-specific
      expression of ganglioside synthase genes. Despite extensive investigations in the
      past, it remains largely unclear how the transcriptional activation of the genes
      encoding glycosyltransferases is regulated. Here, we show that in the
      neuronogenic cultures of mouse embryonic brain-derived neuroepithelial cells,
      histone modifications including acetylated histone H3 and histone H4, but not
      histone H3 trimethylation at lysine 27 of two genes encoding two key regulatory
      GTs, namely, N-acetylgalactosaminyltransferase I and sialyltransferase II, were
      extensively and gradually enhanced, respectively. As a consequence, the level of
      each GT mRNA was increased correspondingly. Hyperacetylation of histones on the
      GalNAcT promoter resulted in recruitment of the trans-activation factors Sp2 and
      AP-1 when cellular histone deacetylases 1 and 2 were knocked down with RNA
      interference or inhibited by treatment with valproic acid. Moreover, epigenetic
      activation of GalNAcT was also detected, as accompanied by a pronounced induction
      of neural differentiation in primary neuroepithelium culture responding to an
      exogenous supplement of ganglioside GM1, a downstream product of the gene's
      encoding enzyme. Our findings thus provide direct evidence of novel pathways for
      ganglioside expression via the epigenetic up-regulation of ganglioside synthase
      genes during neural development. 

PMID- 24102380
TI  - A new smartphone-based method for wound area measurement.
AB  - Proper wound healing can be assessed by monitoring the wound surface area. Its
      reduction by 10 or 50% should be achieved after 1 or 4 weeks, respectively, from
      the start of the applied therapy. There are various methods of wound area
      measurement, which differ in terms of the cost of the devices and their accuracy.
      This article presents an originally developed method for wound area measurement.
      It is based on the automatic recognition of the wound contour with a software
      application running on a smartphone. The wound boundaries have to be traced
      manually on transparent foil placed over the wound. After taking a picture of the
      wound outline over a grid of 1 * 1 cm, the AreaMe software calculates the wound
      area, sends the data to a clinical database using an Internet connection, and
      creates a graph of the wound area change over time. The accuracy and precision of
      the new method was assessed and compared with the accuracy and precision of
      commercial devices: Visitrak and SilhouetteMobile. The comparison was performed
      using 108 wound shapes that were measured five times with each device, using an
      optical scanner as a reference device. The accuracy of the new method was
      evaluated by calculating relative errors and comparing them with relative errors
      for the Visitrak and the SilhouetteMobile devices. The precision of the new
      method was determined by calculating the coefficients of variation and comparing
      them with the coefficients of variation for the Visitrak and the SilhouetteMobile
      devices. A statistical analysis revealed that the new method was more accurate
      and more precise than the Visitrak device but less accurate and less precise than
      the SilhouetteMobile device. Thus, the AreaMe application is a superior
      alternative to the Visitrak device because it provides not only a more accurate
      measurement of the wound area but also stores the data for future use by the
      physician. 

PMID- 24102379
TI  - Whole exome sequencing is an efficient and sensitive method for detection of
      germline mutations in patients with phaeochromcytomas and paragangliomas.
AB  - BACKGROUND: Genetic testing is recommended when the probability of a disease
      associated germline mutation exceeds 10%. Germline mutations are found in
      approximately 25% of individuals with phaeochromcytoma (PCC) or paraganglioma
      (PGL); however, genetic heterogeneity for PCC/PGL means many genes may require
      sequencing. A phenotype-directed iterative approach may limit costs but may also
      delay diagnosis, and will not detect mutations in genes not previously associated
      with PCC/PGL. OBJECTIVE: To assess whether whole exome sequencing (WES) was
      efficient and sensitive for mutation detection in PCC/PGL. METHODS: Whole exome
      sequencing was performed on blinded samples from eleven individuals with PCC/PGL
      and known mutations. Illumina TruSeq (Illumina Inc, San Diego, CA, USA) was used
      for exome capture of seven samples, and NimbleGen SeqCap EZ v3.0 (Roche NimbleGen
      Inc, Basel, Switzerland) for five samples (one sample was repeated). Massive
      parallel sequencing was performed on multiplexed samples. Sequencing data were
      called using Genome Analysis Toolkit and annotated using annovar. Data were
      assessed for coding variants in RET, NF1, VHL, SDHD, SDHB, SDHC, SDHA, SDHAF2,
      KIF1B, TMEM127, EGLN1 and MAX. Target capture of five exome capture platforms was
      compared. RESULTS: Six of seven mutations were detected using Illumina TruSeq
      exome capture. All five mutations were detected using NimbleGen SeqCap EZ v3.0
      platform, including the mutation missed using Illumina TruSeq capture. Target
      capture for exons in known PCC/PGL genes differs substantially between platforms.
      Exome sequencing was inexpensive (<$A800 per sample for reagents) and rapid
      (results <5 weeks from sample reception). CONCLUSION: Whole exome sequencing is
      sensitive, rapid and efficient for detection of PCC/PGL germline mutations.
      However, capture platform selection is critical to maximize sensitivity.

PMID- 24102383
TI  - Supramolecular assemblies based on complexes of nonionic amphiphilic
      cyclodextrins and a meso-tetra(4-sulfonatophenyl)porphine tributyltin(IV)
      derivative: potential nanotherapeutics against melanoma.
AB  - Amphiphilic cyclodextrin (ACyD) provides water-soluble and adaptable nanovectors
      by modulating the balance between the hydrophobic and hydrophilic chains at both
      CyD sides. This work aimed to design nanoassemblies based on nonionic and
      hydrophilic ACyD (SC6OH) for the delivery of a poor-water-soluble organotin(IV)
      porphyrin derivative [(Bu3Sn)4TPPS] to melanoma cancer cells. To characterize the
      porphyrin derivatives under simulated physiological conditions, a speciation was
      performed using complementary techniques. In aqueous solution (<= 20 MUM),
      (Bu3Sn)4TPPS primarily exists as a monomer (2 in Figure 1), as suggested by the
      low static anisotropy (rho ~ 0.02) with a negligible formation of porphyrin
      supramolecular aggregates. MALDI-TOF spectra indicate the presence of moieties
      (i.e., [(Bu3Sn)3TPPS](-)) that are derivatives of the monomeric species.
      Spectrofluorimetry coupled with potentiometric measurements primarily assesses
      the presence of the hydrolytic [(Bu3Sn)4TPPS (OH)4](4-) species under
      physiological conditions. Nanoassemblies of (Bu3Sn)4TPPS/SC6OH were prepared by
      dispersion of organic films in PBS at pH 7.4 and were investigated using a
      combination of spectroscopic and morphological techniques. The UV-vis and
      emission fluorescence spectra of the (Bu3Sn)4TPPS/SC6OH reveal shifts in the
      peculiar bands of the organotin(IV)-porphyrin derivative due to its interaction
      with the ACyD supramolecular assemblies in aqueous solution. The mean size was
      within the range of 100-120 nm. The xi-potential was negative (-16 mV) for the
      (Bu3Sn)4TPPS/SC6OH nanoassemblies, with an entrapment efficiency of approximately
      67%. The intracellular delivery, cytotoxicity, nuclear morphology and cell growth
      kinetics were evaluated via fluorescence microscopy on A375 human melanoma cells.
      The delivery of (Bu3Sn)4TPPS by ACyD with respect to free (Bu3Sn)4TPPS increases
      the internalization efficiency and cytotoxicity to induce apoptotic cell death
      and, at lower concentrations, changes the cellular morphology and prevents cell
      proliferation.

PMID- 24102384
TI  - Effects of erythromycin at steady-state concentrations on the pharmacokinetics of
      ulipristal acetate.
AB  - WHAT IS KNOWN AND OBJECTIVE: Ulipristal acetate (UPA) is a novel selective
      progesterone receptor modulator for the treatment of benign gynaecological
      conditions such as uterine myoma. In vitro, it is mainly metabolized by the
      cytochrome P450 isoenzyme CYP3A4 and to a small extent by CYP1A2 and CYP2D6.
      Erythromycin, a macrolide antibiotic, has been shown to be a moderate CYP3A4
      inhibitor. Thus, the aim of this study was to determine the effects of
      erythromycin at steady-state concentrations on the pharmacokinetics of UPA.
      Effects on the pharmacokinetics of the mono-demethylated metabolite of UPA
      (PGL4002) were also evaluated. METHODS: This was a non-randomized, single
      sequence, two-period, open, single-dose study in 18 healthy female subjects.
      Subjects received oral UPA (20 mg) once daily on days 1 and 13 and twice-daily
      erythromycin propionate administrations (500 mg) from days 9 through 17. RESULTS:
      Geometric mean Cmax and AUCs of UPA were increased by 24% [geometric mean ratio
      point estimate (90% CI): 1.24 (1.01-1.52)] and +224% and +227% [geometric mean
      ratio point estimates (90% CI): AUC0-t 3.24 (2.75-3.83) and AUC0-infinity (3.27
      (2.79-3.83)], respectively, with no effect on median tmax or t1/2. Geometric mean
      Cmax of PGL4002 was decreased by 47% [geometric mean ratio point estimate (90%
      CI): 0.523 (0.44-0.62)], but AUCs were increased by +62% and +66% [geometric mean
      ratio point estimates (90% CI): AUC0-t 1.62 (1.43-1.85) and AUC0-infinity by 1.66
      (1.47-1.88)], respectively, with no effect on median tmax. However, geometric
      mean t1/2.doubled from 24 h to 48 h. No subject was discontinued from the study
      due to adverse events. WHAT IS NEW AND CONCLUSION: Concomitant use of ulipristal
      acetate with erythromycin at therapeutic concentrations led to a limited increase
      in Cmax and a 3-fold increase in AUCs for UPA and to a decrease in Cmax and an
      increase in AUCs and prolonged elimination for PGL4002. This indicates that
      inhibition of CYP3A4 impacted rate and extent of absorption of UPA and also its
      metabolism by slowing the elimination of its metabolite PGL4002.

PMID- 24102385
TI  - Correlations between functional performance, health-related quality of life, and
      parental impact on children with developmental delays.
AB  - OBJECTIVE: To examine the correlation of function, quality of life (QOL), and
      parental impact on developmental delayed children. METHODS: Sixty parents of
      children with developmental delays (M:F = 36:24, mean age 4 years and 2 months)
      and 56 parents of age-sex matched typical development children were included.
      Pediatric Outcomes Data Collection Instrument and Child Health Questionnaire for
      children, World Health Organization-QOL, Impact on Family Scale, and Hospital
      Anxiety and Depression Scale for parents were assessed. RESULTS: Functional
      performance was correlated with physical component of QOL in children
      (correlation coefficients: 0.7-0.9; p < 0.01), age of children (0.3-0.4; p <
      0.05) and parents (0.3; p < 0.05), maternal employment (0.3-0.4; p < 0.05),
      parental QOL (0.3-0.4; p < 0.01), family impact (-0.3 to -0.5; p < 0.01), and
      parental emotion (-0.3 to -0.4; p < 0.05). CONCLUSIONS: Children who exhibited
      higher levels of function had higher QOL, as did their parents, and less parental
      impact.

PMID- 24102386
TI  - Atypical cilia in the respiratory tract of common marmosets (Callithrix jacchus)
      with and without concurrent lung disease.
AB  - Ciliated cells of the respiratory epithelium play an essential role in the
      mechanisms of mucociliary clearance, and ultrastructural alterations of cilia are
      known to be associated with respiratory disease. The aim of this study was to
      evaluate the presence of ciliary changes in common marmosets (Callithrix jacchus)
      of different age groups and to compare healthy animals with animals suffering
      from subclinical chronic inflammatory pulmonary lesions. Therefore, samples of
      different sites of the tracheobronchial tree from 24 common marmosets were
      investigated by transmission electron microscopy. Ciliary alterations were
      present in all animals and were represented by compound cilia ("bulging/adhesive
      type"), extramatrix, extratubuli, and disorientation of the microtubular
      arrangement. Ciliary alterations affected less than 1% of cilia (average 0.06%
      0.55%) with no statistically significant differences between age groups, sample
      localizations, or healthy and sick animals. The study results suggest that
      ciliary alterations of secondary nature are a common background finding in common
      marmosets with individual variability in abundance and have to be considered when
      interpreting ultrastructural data from respiratory studies.

PMID- 24102387
TI  - Brain activation during speech perception in a patient with a massive left
      hemisphere infarction.
AB  - BACKGROUND: Little is known about the regions involved in recovery from global
      aphasia in patients with malignant infarction after decompressive
      hemicraniectomy. This study reports a case of brain activation during speech
      perception in a right-handed patient with a massive left hemispheric infarction.
      METHODS: Decompressive hemicraniectomy was performed in a 20-year old woman with
      space-occupying infarction of the speech dominant hemisphere. Complete anterior,
      middle and part of the posterior cerebral artery territories of the left
      hemisphere, as well as posterior regions of the right middle cerebral artery
      territory, were affected. Neuropsychological testing and functional magnetic
      resonance imaging (fMRI) during speech perception were performed 10 months after
      stroke. RESULTS: The patient was able to walk, go up and down stairs
      independently and perform simple tasks at home. She was also well able to match
      visually and orally presented words with their corresponding pictures, despite
      large bilateral lesions in the posterior regions. fMRI revealed strong activation
      of the left temporo-occipital and parieto-occipital areas. In the right
      hemisphere was observed a small area of activation in the posterior part of the
      superior and middle temporal gyrus. CONCLUSIONS: In aphasic patients, the
      activation of posterior bilateral associative areas might be used to support
      language perception.

PMID- 24102388
TI  - Effects of omalizumab in a patient with three types of chronic urticaria.

PMID- 24102391
TI  - [3:1] site-differentiated [4Fe-4S] clusters having one carboxylate and three
      thiolates.
AB  - [4Fe-4S] clusters modeled after those in organisms having three cysteine
      thiolates and one carboxylate were synthesized by using the tridentate thiolato
      chelate. X-ray structural analysis reveals that the carboxylates coordinate to
      the unique irons in an eta(1) manner rather than eta(2). Redox potentials show a
      positive shift from that of the cluster having ethanethiolate and the tridentate
      thiolato chelate. These properties conform to the arrangement of the [4Fe-4S]
      clusters in the electron transfer systems included in Rc dark operative
      protochlorophyllide oxidoreductase (DPOR) and formaldehyde oxidoreductase (FOR)
      with Pf ferredoxin. 

PMID- 24102390
TI  - Umbilical cord vitamin D, ionized calcium and myocardial oxygen demand.
AB  - OBJECTIVE: Systemic blood vitamin D and total calcium are correlates of
      birthweight and cardiovascular disease but whether umbilical cord blood vitamin D
      and ionized calcium are correlates of birthweight and cardiovascular function is
      not known. This cross-sectional study correlates umbilical cord vitamin D,
      ionized calcium and birthweight with the heart rate-systolic pressure product
      (RPP), an indicator of myocardial oxygen demand. METHODS: Cord blood vitamin D
      and ionized calcium concentrations were compared for vitamin D normal (>=50 nM,
      20 ng/mL) and vitamin D deficiency (<50 nM, 20 ng/mL) in normal weight (>=2500 g)
      and low birthweight (LBW, <2500 g) newborns. Heart rate and blood pressure were
      measured during postnatal transition and RPP was computed. RESULTS: RPP was
      positively correlated with birthweight (r = +0.52, p < 0.001) and with cord
      ionized calcium level (r = +0.42, p < 0.01) in the normal and LBW newborns. RPP
      was positively correlated with cord vitamin D level in the LBW newborns (raw r =
      +0.50, p < 0.05, normalized for birthweight r = +0.73, p < 0.01). CONCLUSIONS:
      Small RPP, an indicator of low myocardial oxygen demand, in LBW newborns appears
      to correlate with low umbilical cord vitamin D and ionized calcium levels,
      suggestive of pathological heart development.

PMID- 24102392
TI  - Palladium catalyzed oxidative coupling of alpha-enolic dithioesters: a new entry
      to 3,4,5-trisubstituted 1,2-dithioles via a double activation strategy.
AB  - An operationally simple, facile, and convenient one-pot straightforward method
      for the construction of 3,4,5-trisubstituted 1,2-dithioles has been explored and
      developed via palladium catalyzed self-coupling of alpha-enolic dithioesters for
      the first time. Pd(0) efficiently catalyzes the activation and cleavage of S-H
      and C-S bonds to achieve cascade coupling, which results in the concomitant
      formation of new S-S and C-C bonds. Optimization data, substrate scope, and
      mechanistic insights are discussed. 

PMID- 24102389
TI  - New insights into the molecular mechanism of intestinal fatty acid absorption.
AB  - BACKGROUND: Dietary fat is one of the most important energy sources of all the
      nutrients. Fatty acids, stored as triacylglycerols (also called triglycerides) in
      the body, are an important reservoir of stored energy and derived primarily from
      animal fats and vegetable oils. DESIGN: Although the molecular mechanisms for the
      transport of water-insoluble amphipathic fatty acids across cell membranes have
      been debated for many years, it is now believed that the dominant means for
      intestinal fatty acid uptake is via membrane-associated fatty acid-binding
      proteins, that is, fatty acid transporters on the apical membrane of enterocytes.
      RESULTS: These findings indicate that intestinal fatty acid absorption is a
      multistep process that is regulated by multiple genes at the enterocyte level,
      and intestinal fatty acid absorption efficiency could be determined by factors
      influencing intraluminal fatty acid molecules across the brush border membrane of
      enterocytes. To facilitate research on intestinal, hepatic and plasma
      triacylglycerol metabolism, it is imperative to establish standard protocols for
      precisely and accurately measuring the efficiency of intestinal fatty acid
      absorption in humans and animal models. In this review, we will discuss the
      chemical structure and nomenclature of fatty acids and summarize recent progress
      in investigating the molecular mechanisms underlying the intestinal absorption of
      fatty acids, with a particular emphasis on the physical chemistry of intestinal
      lipids and the molecular physiology of intestinal fatty acid transporters.
      CONCLUSIONS: A better understanding of the molecular mechanism of intestinal
      fatty acid absorption should lead to novel approaches to the treatment and the
      prevention of fatty acid-related metabolic diseases that are prevalent worldwide.

PMID- 24102394
TI  - Radiofrequency ablation lesion detection using MR-based electrical conductivity
      imaging: a feasibility study of ex vivo liver experiments.
AB  - PURPOSE: The aim of this study was to show the potential of magnetic resonance
      electrical impedance tomography (MREIT) conductivity imaging in terms of its
      capability to detect ablated lesions and differentiate tissue conditions in liver
      radiofrequency (RF) ablation. MATERIALS AND METHODS: RF ablation procedures were
      performed in bovine livers using a LeVeen RF needle electrode. Ablation lesions
      were created using a power-controlled mode at 30, 50, and 70 W for 1, 3, and 5
      min of exposure time, respectively. After the ablation, the liver was cut into
      several blocks including the ablated lesion, and positioned inside a phantom
      filled with agarose gel. Electrodes were attached on the side of the phantom and
      it was placed inside the MRI bore. For MREIT imaging, multi-spin-echo pulse
      sequence was used to obtain the magnetic flux density data according to the
      injection currents. RESULTS: The conductivity of ablation lesions was
      significantly changed with the increase of exposure time (pKW < 0.01, Kruskal
      Wallis test). With RF powers of 30 and 50 W, significant differences between the
      coagulation necrosis and hyperaemic rim were observed for more than 5 min and 3
      min, respectively (pMW < 0.01, Mann-Whitney test). At 70 W, all cases showed
      significant differences except 3 min (pMW < 0.01). The positive correlation
      between the exposure time and tissue conductivity was observed in both two
      ablation areas (pSC < 0.01, Spearman correlation). CONCLUSIONS: This ex vivo
      feasibility study demonstrates that current MREIT conductivity imaging can detect
      liver RF ablation lesions without using any contrast media or additional MR scan.

PMID- 24102393
TI  - Approaches for modelling interstitial ultrasound ablation of tumours within or
      adjacent to bone: theoretical and experimental evaluations.
AB  - PURPOSE: The objectives of this study were to develop numerical models of
      interstitial ultrasound ablation of tumours within or adjacent to bone, to
      evaluate model performance through theoretical analysis, and to validate the
      models and approximations used through comparison to experiments. METHODS: 3D
      transient biothermal and acoustic finite element models were developed, employing
      four approximations of 7-MHz ultrasound propagation at bone/soft tissue
      interfaces. The various approximations considered or excluded reflection,
      refraction, angle-dependence of transmission coefficients, shear mode conversion,
      and volumetric heat deposition. Simulations were performed for parametric and
      comparative studies. Experiments within ex vivo tissues and phantoms were
      performed to validate the models by comparison to simulations. Temperature
      measurements were conducted using needle thermocouples or magnetic resonance
      temperature imaging (MRTI). Finite element models representing heterogeneous
      tissue geometries were created based on segmented MR images. RESULTS: High
      ultrasound absorption at bone/soft tissue interfaces increased the volumes of
      target tissue that could be ablated. Models using simplified approximations
      produced temperature profiles closely matching both more comprehensive models and
      experimental results, with good agreement between 3D calculations and MRTI. The
      correlation coefficients between simulated and measured temperature profiles in
      phantoms ranged from 0.852 to 0.967 (p-value < 0.01) for the four models.
      CONCLUSIONS: Models using approximations of interstitial ultrasound energy
      deposition around bone/soft tissue interfaces produced temperature distributions
      in close agreement with comprehensive simulations and experimental measurements.
      These models may be applied to accurately predict temperatures produced by
      interstitial ultrasound ablation of tumours near and within bone, with
      applications toward treatment planning.

PMID- 24102395
TI  - The value of artificial pleural effusion for percutaneous microwave ablation of
      liver tumour in the hepatic dome: a retrospective case-control study.
AB  - PURPOSE: The aim of this study was to evaluate the feasibility, safety, and
      efficiency of percutaneous microwave ablation (MWA) with artificial pleural
      effusion for liver tumours located in the hepatic dome. MATERIALS AND METHODS: A
      total of 112 sessions of artificial pleural effusion performed on 102 liver
      tumour patients were summarised and analysed at our hospital. Among them, 31
      hepatocellular carcinoma patients treated by percutaneous MWA were selected as
      the artificial pleural effusion group. The control group without artificial
      pleural effusion was matched with tumour size, tumour location and the
      histological grades of differentiation. The primary technique effectiveness rate,
      local tumour progression rate and tumour-free survival rate were compared.
      RESULTS: Artificial pleural effusion was achieved successfully in 110 of 112
      sessions (98.2%), which helped to improve the visibility in 98.8% (82/83) and
      acquire safe puncture path in 96.3% (26/27). There were no statistical
      differences between the artificial pleural effusion group and the control group
      in the primary technique effectiveness rate (p = 1.000), the 1-, 2-, and 3-year
      local tumour progression rates (p = 0.669), and the 1-, 2-, and 3-year tumour
      free survival rates (p = 0.979). CONCLUSIONS: Percutaneous MWA with artificial
      pleural effusion could be a feasible, safe, and effective technique for liver
      tumours located in the hepatic dome.

PMID- 24102396
TI  - Advances of high intensity focused ultrasound (HIFU) for pancreatic cancer.
AB  - High intensity focused ultrasound (HIFU) is a novel therapeutic modality. Several
      preclinical and clinical studies have investigated the safety and efficacy of
      HIFU for treating solid tumours, including pancreatic cancer. Preliminary studies
      suggest that HIFU may be useful for the palliative therapy of cancer-related pain
      in patients with unresectable pancreatic cancer. This review provides a brief
      overview of HIFU, describes current clinical applications of HIFU for pancreatic
      cancer, and discusses future applications and challenges.

PMID- 24102397
TI  - Primary malignant tumours of the bony pelvis: US-guided high intensity focused
      ultrasound ablation.
AB  - PURPOSE: The aim of this review is to evaluate the value of ultrasound (US)
      guided high intensity focused ultrasound (HIFU) ablation in the treatment of
      primary malignant tumours of the bony pelvis. MATERIALS AND METHODS: Eleven
      patients with primary malignant tumours of the bony pelvis received US-guided
      HIFU ablation. The maximum tumour size ranged from 5.6 to 25.0 cm (median 10.5
      cm). Treatment was curative in four patients and palliative in seven patients.
      During follow-up, the effectiveness of HIFU ablation was assessed by contrast
      enhanced magnetic resonance (MR). RESULTS: Significant coagulative necrosis was
      obtained in all patients after scheduled HIFU ablations; the volume ablation
      ratio was 86.7% +/- 12.5% (range 65-100%). Complete tumour necrosis was achieved
      in all patients receiving curative HIFU ablation. No major complications were
      encountered. No patients died of local tumour progression during follow-up.
      CONCLUSIONS: US-guided HIFU ablation may be a safe and effective minimally
      invasive technique for the local treatment of primary malignant tumours of the
      bony pelvis.

PMID- 24102399
TI  - Trapping of hydrochloric and hydrofluoric acid at vacancies on and underneath the
      ice I(h) basal-plane surface.
AB  - We investigate the uptake of HCl and HF at lattice vacancies in ice Ih as a
      function of their distance to the basal-plane surface layer using density
      functional theory calculations. The results for HCl display large dispersions in
      the binding-energy results due to the appearance of distinct dissociation states.
      The layer-averaged results suggest that the uptake of HCl is most favorable in
      the two layers just below the surface, which is consistent with available
      experimental indications. The behavior of HF is found to be manifestly different
      due to the fact that it is a weaker acid. The dispersion in the binding-energy
      values is significantly less compared to the case of HCl, and the average values
      are essentially equal to the bulk value, regardless of layer position. This
      suggests that, in contrast to the case of HCl, there should not be any tendency
      for accumulation of HF near the surface. 

PMID- 24102398
TI  - Effects of mammalian in utero heat stress on adolescent body temperature.
AB  - In utero hyperthermia can cause a variety of developmental issues, but how it
      alters mammalian body temperature during adolescence is not well-understood.
      Study objectives were to determine the extent to which in utero hyperthermia
      affects future phenotypic responses to a heat load. Pregnant first parity pigs
      were exposed to thermal neutral (TN) or heat stress (HS) conditions during the
      entire gestation. Of the resultant offspring, 12 were housed in TN conditions,
      and 12 were maintained in HS conditions for 15 days. Adolescent pigs in HS
      conditions had increased rectal temperature and respiration rate (RR) compared to
      TN pigs, regardless of gestational treatment. Within the HS environment, no
      gestational difference in RR was detected; however, GHS pigs had increased rectal
      temperature compared to GTN pigs. As rectal temperature increased, GTN pigs had a
      more rapid increase in RR compared to the GHS pigs. Adolescent HS decreased
      nutrient intake, and body weight gain, but neither variable was statistically
      influenced by gestational treatments. In summary, in utero HS compromises the
      future thermoregulatory response to a thermal insult.

PMID- 24102400
TI  - Proceedings of the November 2011 Traceability Research Summit: this report is the
      third in a series on Traceability Summits sponsored by IFT beginning in July
      2011.
AB  - Fifty thought leaders in the area of food traceability met for a 3rd time to
      discuss methodologies and finalize the principles that define their vision for
      traceability. Participants in the summit included representatives from industry,
      trade associations, government, academia, consumer groups, and more. One main
      focus of this summit included a discussion on the current regulations and
      voluntary initiatives in place regarding traceability. Overall, it was recognized
      that the recommendations from this summit group would be more specific and
      stringent in comparison to these current regulations and initiatives. The
      participants sought to be leaders in the traceability arena, with their
      recommendations leading the industry to optimal traceability systems and methods.
      Participants agreed on many principles for their vision of traceability,
      emphasizing the importance of access to traceability data. They discussed having
      industry be asked for "basic" tracing data prior to the need for a large-scale
      investigation, having standards for sharing data, and having the data in
      electronic form. Participants foresaw the importance of capturing data
      electronically in the future, although they recognized that many firms do not
      currently do this. The group also saw a need for a transition period to implement
      changes, and to provide implementation training and resource aid to small
      businesses. Summit participants discussed specific definitions and examples for
      key data elements and critical tracking events that could be used by industry to
      capture tracing data at specific points within the supply chain. Overall,
      participants refined the goals of the summit group and started to identify
      specific ways to achieve those goals. 

PMID- 24102401
TI  - Activation of platelets by the endocannabinoids 2-arachidonoylglycerol and
      virodhamine is mediated by their conversion to arachidonic acid and thromboxane
      A2, not by activation of cannabinoid receptors.

PMID- 24102404
TI  - Global clinical response in Cushing's syndrome patients treated with
      mifepristone.
AB  - OBJECTIVE: Mifepristone, a glucocorticoid receptor antagonist, improves clinical
      status in patients with Cushing's syndrome (CS). We examined the pattern,
      reliability and correlates of global clinical response (GCR) assessments during a
      6-month clinical trial of mifepristone in CS. DESIGN: Post hoc analysis of
      secondary end-point data from a 24-week multicentre, open-label trial of
      mifepristone (300-1200 mg daily) in CS. Intraclass correlation coefficient (ICC)
      was used to examine rater concordance, and drivers of clinical improvement were
      determined by multivariate regression analysis. PATIENTS: Forty-six adult
      patients with refractory CS along with diabetes mellitus type 2 or impaired
      glucose tolerance, and/or a diagnosis of hypertension. MEASUREMENTS: Global
      clinical assessment made by three independent reviewers using a three-point
      ordinal scale (+1 = improvement; 0 = no change; -1 = worsening) based on eight
      broad clinical categories including glucose control, lipids, blood pressure, body
      composition, clinical appearance, strength, psychiatric/cognitive symptoms and
      quality of life at Weeks 6, 10, 16, and 24. RESULTS: Positive GCR increased
      progressively over time with 88% of patients having improved at Week 24 (P <
      0.001). The full concordance among reviewers occurred in 76.6% of evaluations
      resulting in an ICC of 0.652 (P < 0.001). Changes in body weight (P < 0.0001),
      diastolic blood pressure (P < 0.0001), two-hour postoral glucose challenge
      glucose concentration (P = 0.0003), and Cushingoid appearance (P = 0.022) were
      strong correlates of GCR. CONCLUSIONS: Mifepristone treatment for CS results in
      progressive clinical improvement. Overall agreement among clinical reviewers was
      substantial and determinants of positive GCR included change in weight, blood
      pressure, glucose levels and appearance.

PMID- 24102405
TI  - Tidal expiratory flow limitation at rest as a functional marker of pulmonary
      emphysema in moderate-to-severe COPD.
AB  - BACKGROUND: Tidal expiratory flow limitation (EFL) is a step of paramount
      importance in the functional decline in COPD. Among mechanisms contributing to
      EFL, loss of airway-parenchymal interdependence could mostly be involved. AIM: To
      assess if EFL is a functional marker more frequently linked to prevalent
      pulmonary emphysema rather than to prevalent chronic bronchiolitis in COPD
      patients with moderate-to-severe airflow obstruction. METHODS: Forty consecutive
      stable COPD patients with FEV1 between 59 and 30% of predicted were functionally
      evaluated by measuring spirometry, maximal flow-volume curve and lung diffusion
      capacity (DLCO) and coefficient of diffusion (KCO). EFL was assessed by the
      negative expiratory pressure (NEP) method both in sitting and supine position.
      Chronic dyspnea was also scored by modified Medical Research Council (mMRC)
      scale. RESULTS: In sitting position 13 patients (33%) were flow limited (FL) and
      27 were non-flow limited (NFL). Only FEV1/FVC, FEV1 and MEF25-75% were different
      between FL and NFL patients (p < 0.01). In supine position, however, among NFL
      patients in sitting position those who developed EFL, had significantly lower
      values of DLCO and KCO (p < 0.05) and higher mMRC score (p < 0.01), but similar
      values of FEV1 as compared to those who did not have EFL. CONCLUSIONS: In COPD
      EFL in sitting position is highly dependent by the severity of airflow
      obstruction. In contrast, the occurrence of EFL in supine position is associated
      with worse DLCO and KCO and greater chronic dyspnea, reflecting a prevalent
      emphysematous phenotype in moderate-to-severe COPD patients.

PMID- 24102406
TI  - Anti-IL-6 treatment for inflammatory bowel diseases: next cytokine, next target.
AB  - Inflammatory bowel diseases (IBD) are chronic, relapsing, and destructive
      inflammatory disorders of the gastrointestinal tract. Both Crohn's disease (CD)
      and ulcerative colitis (UC) seem to arise from an impaired dialog between the
      environment and gut microbiota in genetically susceptible hosts, leading to an
      inappropriate immune activation and resulting in the over-production of pro
      inflammatory cytokines. IL-6 is a key modulator of inflammatory response. It is a
      phylogenetically important cytokine with relevance in IBD, as well as in other
      chronic inflammatory diseases and cancer. Influencing the production of this
      cytokine can change the balance of effector CD4+ T cell subsets and induce B cell
      antibody production. Moreover, given IL-6 is mostly produced from innate immune
      cells such as macrophages, neutrophils and mast cells, it is a strategic bridge
      between the innate and the adaptive system. Interestingly, IL-6 induced signaling
      can be primarily seen in a relatively small number of IL-6 responsive cells
      whereas in a chronic phase of inflammation it is able to activate almost all
      cells of the body through a process known as trans-signaling. In this review, we
      discuss the role of IL-6 in chronic inflammation, with particular emphasis on its
      role in CD and UC, and we explore the potential to develop anti-IL-6 agents for
      IBD treatment. 

PMID- 24102407
TI  - The RNA-dependent-RNA polymerase, an emerging antiviral drug target for the
      Hendra virus.
AB  - Australia is facing a major national medical challenge with the emergence of the
      Hendra virus (HeV) as a medically and economically important pathogen of humans
      and animals. Clinical symptoms of human HeV infection can include fever,
      hypotension, dizziness, encephalitis, respiratory haemorrhage and edema. The
      window of opportunity for successful patient treatment remains unknown, but is
      likely to be very narrow. Currently, very few effective therapeutic options are
      available for the case management of severe HeV infections or the rapid silencing
      of local outbreaks. This underscores the need for more activity in the drug
      discovery arena to develop much needed therapeutics that specifically targets
      this deadly disease. The structural analysis of HeV is very much in its infancy,
      which leaves many gaps in our understanding of the biology of HeV and makes
      structure-guided drug design difficult. Structural studies of the viral
      RNAdependent- RNA polymerase (RdRp), which is the heart of the viral replication
      machinery, will set the stage for rational drug design and fill a major gap in
      our understanding of the HeV replication machinery. This review examines the
      current knowledge based on the multi-domain architecture of the Hendra RdRp and
      highlights which essential domain functions represent tangible targets for drug
      development against this deadly disease. 

PMID- 24102408
TI  - Has Medicare Part D reduced racial/ethnic disparities in prescription drug use
      and spending?
AB  - OBJECTIVE: To evaluate whether Medicare Part D has reduced racial/ethnic
      disparities in prescription drug utilization and spending. DATA: Nationally
      representative data on white, African American, and Hispanic Medicare seniors
      from the 2002-2009 Medical Expenditure Panel Survey are analyzed. Five measures
      are examined: filling any prescriptions during the year, the number of
      prescriptions filled, total annual prescription spending, annual out-of-pocket
      prescription spending, and average copay level. STUDY DESIGN: We apply the
      Institute of Medicine's definition of a racial/ethnic disparity and adopt a
      difference-in-difference-in-differences (DDD) estimator using a multivariate
      regression framework. The treatment group consists of Medicare seniors, the
      comparison group, adults without Medicare aged 55-63 years. PRINCIPAL FINDINGS:
      Difference-in-difference-in-differences estimates suggest that for African
      Americans Part D increased the disparity in annual spending on prescription drugs
      by $258 (p=.011), yet had no effect on other measures of prescription drug
      disparities. For Hispanics, DDD estimates suggest that the program reduced the
      disparities in annual number of prescriptions filled, annual total and out-of
      pocket spending on prescription drugs by 2.9 (p=.077), $282 (p=.019) and $143
      (p<.001), respectively. CONCLUSION: Medicare Part D had mixed effects. Although
      it reduced Hispanic/white disparities related to prescription drugs among
      seniors, it increased the African American/white disparity in total annual
      spending on prescription drugs.

PMID- 24102409
TI  - Generation of bioartificial heart tissue by combining a three-dimensional gel
      based cardiac construct with decellularized small intestinal submucosa.
AB  - The in vitro generation of a bioartificial cardiac construct (CC) represents a
      promising tool for the repair of ischemic heart tissue. Several approaches to
      engineer cardiac tissue in vitro have been conducted. The main drawback of these
      studies is the insufficient size of the resulting construct for clinical
      applications. The focus of this study was the generation of an artificial three
      dimensional (3D), contractile, and suturable myocardial patch by combining a gel
      based CC with decellularized porcine small intestinal submucosa (SIS), thereby
      engineering an artificial tissue of 11 cm2 in size. The alignment and morphology
      of rat neonatal cardiomyocytes (rCMs) in SIS-CC complexes were investigated as
      well as the re-organization of primary endothelial cells which were co-isolated
      in the rCM preparation. The ability of a rat heart endothelial cell line (RHE-A)
      to re-cellularize pre-existing vessel structures within the SIS or a biological
      vascularized matrix (BioVaM) was determined. SIS-CC contracted spontaneously,
      uniformly, and rhythmically with an average rate of 200 beats/min in contrast to
      undirected contractions observed in CC without SIS support. rCM exhibited an
      elongated morphology with well-defined sarcomeric structures oriented along the
      longitudinal axis in the SIS-CC, whereas round-shaped and random-arranged rCM
      were observed in CC. Electric coupling of rCM was demonstrated by microelectrode
      array measurements. A dense network of CD31+/eNOS+ cells was detected as
      permeating the whole construct. Superficial supplementation of RHE-A cells to SIS
      CC led to the migration of these cells through the CC, resulting in the re
      population of pre-existing vessel structures within the decelluarized SIS. By
      infusion of RHE-A cells into the BioVaM venous and arterial pedicles, a re
      population of the BioVaM vessel bed as well as distribution of RHE-A cells
      throughout the CC was achieved. Rat endothelial cells within the CC were in
      contact with RHE-A cells. Ingrowth and formation of a network by endothelial
      cells infused through the BioVaM represent a promising step toward engineering a
      functional perfusion system, enabling the engineering of vascularized and well
      nourished 3D CC of dimensions relevant for therapeutic heart repair.

PMID- 24102410
TI  - Magnetic interactions in molecules and highly correlated materials: physical
      content, analytical derivation, and rigorous extraction of magnetic Hamiltonians.

PMID- 24102411
TI  - Risk of death associated with the use of conventional vs. atypical antipsychotic
      medications: evaluating the use of the Emilia-Romagna Region database for
      pharmacoepidemiological studies.
AB  - WHAT IS KNOWN AND OBJECTIVE: Since 2005, a mounting base of evidence has
      identified that conventional antipsychotic medications are associated with an
      increased risk of mortality among elderly patients when compared to atypical
      antipsychotics. This study sought to explore the feasibility of using the Emilia
      Romagna Region (RER) database for comparative safety analyses by replicating and
      refining risk estimates of this well-known drug safety example through meta
      analysis. METHODS: We identified a cohort of 23 681 Italian RER patients (aged
      >=65) who initiated treatment with a conventional or atypical antipsychotic
      between 1 July 2009 and 30 June 2011. We compared 180-day mortality using Cox
      proportional hazards models adjusted for risk factors for death, use of other
      medications and measures of health services utilization intensity, all measured
      before antipsychotic initiation. We conducted a meta-analysis of studies with
      similar methods against which to compare our results. RESULTS: Among 14 462 and
      9219 patients prescribed conventional and atypical antipsychotics, respectively,
      we observed 2402 (16.6%) and 821 (8.9%) deaths during follow-up. Conventional
      antipsychotic initiators were older and generally had higher prevalence of
      outcome risk factors and higher baseline health service use intensity. The crude
      hazard ratio (HR) was 1.95 [95% confidence interval (CI), 1.80-2.11], which
      decreased to 1.47 (95% CI, 1.35-1.60) after full adjustment. We identified seven
      published studies that examined this association using similar methods. The
      pooled HR from these studies was 1.34 (95% CI, 1.28-1.39). Including our study,
      the meta-analysis yielded a summary estimate of 1.35 (95% CI, 1.31-1.40) and did
      not introduce any heterogeneity (I(2)  = 0%; P = 0.455). WHAT IS NEW AND
      CONCLUSIONS: Our results support the use of the RER database for
      pharmacoepidemiological studies and provide an up-to-date and pooled estimate of
      the magnitude of the association between mortality and conventional vs. atypical
      antipsychotics.

PMID- 24102412
TI  - Minimalist hybrid ligand/receptor-based pharmacophore model for CXCR4 applied to
      a small-library of marine natural products led to the identification of
      phidianidine a as a new CXCR4 ligand exhibiting antagonist activity.
AB  - Here, we present a minimal hybrid ligand/receptor-based pharmacophore model (PM)
      for CXCR4, a chemokine receptor deeply involved in several pathologies, such as
      HIV infection, rheumatoid arthritis, cancer development/progression, and
      metastasization. This model, considerably simpler than those thus far proposed
      for this receptor, has been used to search for new CXCR4 inhibitors in a small
      marine natural product library available at ICB-CNR Institute (Pozzuoli, NA,
      Italy), since natural products, with their naturally selected chemical and
      functional diversity, represent a rich source of bioactive scaffolds;
      computational approaches allow searching for new scaffolds with a minimal waste
      of possibly precious natural product samples; and our "stripped-down" model
      substantially increases the probabilities of identifying potential hits even in
      small-sized libraries. This search, also validated by a systematic virtual
      screening of the same library, has led to the identification of a new CXCR4
      ligand, phidianidine A (PHIA). Docking studies supported PHIA activity and
      suggested its possible binding modes to CXCR4. Using the CXCR4-expressing/CXCR7
      negative GH4C1 cell line we show that PHIA inhibits CXCL12-induced DNA synthesis,
      cell migration, and ERK1/2 activation. The specificity of these effects was
      confirmed by the lack of PHIA activity in GH4C1 cells, in which siRNA highly
      reduces CXCR4 expression and the lack of cytoxicity of PHIA was also verified.
      Thus, PHIA represents a promising lead for a new family of CXCR4 modulators with
      wide margins of improvement in potency and specificity offered by the small and
      very simple underlying PM. 

PMID- 24102413
TI  - Emerging treatments for hepatitis C.
AB  - INTRODUCTION: About 2.35% of the world population can be infected with hepatitis
      C virus (HCV) responsible for chronic hepatitis, liver cirrhosis and
      hepatocellular carcinoma. Currently available interferon-based medication is
      successful in up to 75% of the patients infected with HCV genotypes 1, 2 or 3 and
      lower efficacy in other genotypes. Unfortunately sustained virologic response
      (SVR) rate in genotype 1 infected non-responders to previous therapy with
      advanced hepatic fibrosis even after retreatment with the first generation direct
      acting antivirals (DAA) is about 40% only. AREAS COVERED: The second generation
      DAA, which have recently been submitted for registration (Sofosbuvir and
      Simeprevir) still need combination with PegIFNalpha and RBV in patients infected
      with HCV genotype 1. There is a need for more effective antiviral therapy for
      difficult to treat patients who are interferon intolerant, developed liver
      cirrhosis or non-responders to previous therapies. Therefore, IFN-free regimens
      are step for future therapies consisting of combinations of novel investigational
      DAA and host targeting agents. EXPERT OPINION: The introduction of novel DAA with
      a good safety profile and high barrier to resistance can lead to SVR rates
      exceeding 90% in treatment naive patients and non-responders to previous therapy
      infected with different genotypes.

PMID- 24102414
TI  - Distinct genetic aberrations in oesophageal adeno and squamous carcinoma.
AB  - BACKGROUND: The two main oesophageal cancer subtypes namely adenocarcinoma and
      squamous cell carcinoma exhibit interesting clinical, pathological and
      geographical variations with the former being more common in the West and the
      latter in Asia. MATERIALS AND METHODS: We evaluated status of p53, EGFR, Wnt and
      HPV in addition to microsatellite instability and loss of heterozygosity of
      several chromosomal loci in the two oesophageal cancer subtypes from India. The
      comparative analysis was extended to two oesophageal adenosquamous mixed cancer
      samples. RESULTS: Our results reveal a high frequency of EGFR overexpression in
      ESCC as against EAC, while Wnt activation was a significantly more common event
      in EAC as against ESCC. Frequencies of p53 perturbations were not significantly
      different in the two subtypes. Interestingly, the EGFR and Wnt status in
      adenocarcinoma and squamous components of the two oesophageal adenosquamous
      cancer samples were identical to primary tumours. In addition, no common
      molecular aberration (including instability and loss of heterozygosity) in
      several microsatellites was detected in DNA isolated from the two components in
      both adenosquamous cancer samples. CONCLUSIONS: Our results reveal the presence
      of distinct aberrations in oesophageal adenocarcinoma and squamous cell carcinoma
      which are replicated in the respective components of adenosquamous cancers. The
      study therefore suggests perhaps an independent origin of the two components of
      oesophageal adenosquamous mixed cancer.

PMID- 24102415
TI  - Combinatorial functions of diverse histone methylations in Arabidopsis thaliana
      flowering time regulation.
AB  - Previous studies in Arabidopsis thaliana have identified several histone
      methylation enzymes, including Arabidopsis trithorax1 (ATX1)/set domain group 27
      (SDG27), ATX2/SDG30, LSD1-LIKE1 (LDL1), LDL2, SDG8, SDG25, and curly leaf
      (CLF)/SDG1, as regulators of the key flowering repressor flowering locus C (FLC)
      and the florigen flowering locus T (FT). However, the combinatorial functions of
      these enzymes remain largely uninvestigated. Here, we investigated functional
      interplays of different histone methylation enzymes by studying higher order
      combinations of their corresponding gene mutants. We showed that H3K4me2/me3 and
      H3K36me3 depositions occur largely independently and that SDG8-mediated H3K36me3
      overrides ATX1/ATX2-mediated H3K4me2/me3 or LDL1/LDL2-mediated H3K4 demethylation
      in regulating FLC expression and flowering time. By contrast, a reciprocal
      inhibition was observed between deposition of the active mark H3K4me2/me3 and/or
      H3K36me3 and deposition of the repressive mark H3K27me3 at both FLC and FT
      chromatin; and the double mutants sdg8 clf and sdg25 clf displayed enhanced early
      flowering phenotypes of the respective single mutants. Collectively, our results
      provide important insights into the interactions of different types of histone
      methylation and enzymes in the regulation of FLC and FT expression in flowering
      time control.

PMID- 24102417
TI  - Repair of left ventricular assist device driveline damage directly at the
      transcutaneous exit site.
AB  - With increasing support duration of cardiac assist devices, transcutaneous
      drivelines remain a weak point of the therapy. First, they can be an entry point
      for infections, and second, cable lesions and even electrical failures due to
      material fatigue and eventual carelessness can occur. We report a case of a
      damaged outer sheath of a ventricular assist device driveline cable directly at
      the exit site, where the standard repair procedure with self-fusing tape may lead
      to biocompatibility problems and irritation of the entrance through the skin.
      Therefore, a new procedure was developed using a special sleeve expander tool and
      a highly expandable latex tubing to stabilize the defect in a flexible and
      biocompatible manner. A patient experienced a fracture of the outer sheath of a
      HeartWare HVAD driveline directly at the skin entrance (approximately 15 mm long,
      5 mm distal from the skin). The metal strands and the electrical functionality
      were yet not affected, therefore, a pump exchange was not indicated. After
      considering several conventional solutions for repair as not applicable, a new
      approach was developed: a sleeve expander tool was applied, which allowed radial
      stretching of the latex tubing. After preparations of the tool and the cable
      site, the pump was briefly disconnected, the tubing was moved over the connector
      and was released at the site of fracture. The problem could be solved by keeping
      the cable's flexibility and without additional risks to the skin. Within a still
      ongoing (5-month) follow-up, the skin entrance returned to perfect condition and
      no further intervention was necessary. In conclusion, this method allows a quick
      stabilization and repair of damaged driveline isolations even near the exit site,
      resulting in a biocompatible surface and consistent flexibility of the cable. 

PMID- 24102416
TI  - Management of chronic hypertension during pregnancy with furosemide, amlodipine
      or aspirin: a pilot clinical trial.
AB  - OBJECTIVE: To determine the maternal and neonatal efficacy and safety with
      furosemide, amlodipine or aspirin in women with mild/moderate chronic
      hypertension during pregnancy. METHODS: A pilot clinical trial was performed in a
      tertiary teaching hospital in Panama. Pregnant patients with mild/moderate
      chronic hypertension at <=20 weeks of gestation were invited to take part in the
      study. Mild/moderate chronic hypertension was defined as a pregnancy with
      systolic blood pressure of 140-159 mmHg or diastolic blood pressure of 90-109
      mmHg. Women in the furosemide group received 20 mg of furosemide oral each day,
      those in the amlodipine group received 5 mg of amlodipine oral each day and those
      in the aspirin group received 75 mg of orally-administered acetylsalicylic acid
      each day. RESULTS: We enrolled 63 patients during the study period, 21 women were
      randomised to each group (aspirin, amlodipine and furosemide). We found no
      difference in maternal complications, pre-term births, mean birth weight or in
      the proportion of small for gestational age infants among treatment groups.
      Severe hypertension and aggregate pre-eclampsia were similar among treatment
      groups. CONCLUSION: This pilot trial demonstrates that both furosemide and
      amlodipine might have the same effect during pregnancy. However, a large clinical
      trial is necessary to prove this.

PMID- 24102418
TI  - The influence of bleaching agent and temperature on bleaching efficacy and
      volatile components of fluid whey and whey retentate.
AB  - Fluid whey or retentate are often bleached to remove residual annatto Cheddar
      cheese colorant, and this process causes off-flavors in dried whey proteins. This
      study determined the impact of temperature and bleaching agent on bleaching
      efficacy and volatile components in fluid whey and fluid whey retentate. Freshly
      manufactured liquid whey (6.7% solids) or concentrated whey protein (retentate)
      (12% solids, 80% protein) were bleached using benzoyl peroxide (BP) at 100 mg/kg
      (w/w) or hydrogen peroxide (HP) at 250 mg/kg (w/w) at 5  degrees C for 16 h or 50
      degrees CC for 1 h. Unbleached controls were subjected to a similar temperature
      profile. The experiment was replicated three times. Annatto destruction
      (bleaching efficacy) among treatments was compared, and volatile compounds were
      extracted and separated using solid phase microextraction gas chromatography mass
      spectrometry (SPME GC-MS). Bleaching efficacy of BP was higher than HP (P < 0.05)
      for fluid whey at both 5 and 50  degrees C. HP bleaching efficacy was increased
      in retentate compared to liquid whey (P < 0.05). In whey retentate, there was no
      difference between bleaching with HP or BP at 50 or 5  degrees C (P > 0.05).
      Retentate bleached with HP at either temperature had higher relative abundances
      of pentanal, hexanal, heptanal, and octanal than BP bleached retentate (P <
      0.05). Liquid wheys generally had lower concentrations of selected volatiles
      compared to retentates. These results suggest that the highest bleaching efficacy
      (within the parameters evaluated) in liquid whey is achieved using BP at 5 or 50 
      degrees C and at 50  degrees C with HP or BP in whey protein retentate. 

PMID- 24102419
TI  - Suppression of glycolate oxidase causes glyoxylate accumulation that inhibits
      photosynthesis through deactivating Rubisco in rice.
AB  - Glycolate oxidase (GLO) is a key enzyme for photorespiration in plants. Previous
      studies have demonstrated that suppression of GLO causes photosynthetic
      inhibition, and the accumulated glycolate with the deactivated Rubisco is likely
      involved in the regulation. Using isolated Rubisco and chloroplasts, it has been
      found that only glyoxylate can effectively inactivate Rubisco and meanwhile
      inhibit photosynthesis, but little in vivo evidence has been acquired and
      reported. In this study, we have generated the transgenic rice (Oryza sativa)
      plants with GLO being constitutively silenced, and conducted the physiological
      and biochemical analyses on these plants to explore the regulatory mechanism.
      When GLO was downregulated, the net photosynthetic rate (Pn) was reduced and the
      plant growth was correspondingly stunted. Surprisingly, glyoxylate, as a product
      of the GLO catalysis, was accumulated in response to the GLO suppression, like
      its substrate glycolate. Furthermore, the glyoxylate content was found to be
      inversely proportional to the Pn while the Pn is directly proportional to the
      Rubisco activation state in the GLO-suppressed plants. A mathematical fitting
      equation using least square method also demonstrated that the Rubisco activation
      state was inversely proportional to the glyoxylate content. Despite that the
      further analyses we have conducted failed to reveal how glyoxylate was
      accumulated in response to the GLO suppression, the current results do strongly
      suggest that there may exist an unidentified, alternative pathway to produce
      glyoxylate, and that the accumulated glyoxylate inhibits photosynthesis by
      deactivating Rubisco, and causes the photorespiratory phenotype in the GLO
      suppressed rice plants. 

PMID- 24102420
TI  - Improvement in precision of counting actinic keratoses.
AB  - BACKGROUND: Actinic keratoses (AKs) often serve as a primary endpoint for
      clinical studies. However, reliability of counting these lesions is poor, even
      among expert dermatologists. OBJECTIVES: To investigate the reliability of
      counting AKs before and after a yearly consensus meeting, held annually for 4
      years. METHODS: As part of the Veterans Affairs (VA) Keratinocyte Carcinoma
      Chemoprevention Trial, board-certified dermatologists convened annually for 4
      years to individually count the number of actinic keratoses on three to five test
      subjects. The dermatologists then met as a group for a consensus discussion on
      what constituted an AK lesion on each subject. Afterwards, each dermatologist
      repeated the independent counting exercise on three to five new subjects. The
      intraclass correlation coefficient (ICC) was used to analyze the reliability of
      counting AKs among the dermatologists. RESULTS: Eight dermatologists participated
      in this exercise for 4 consecutive years. Pre-consensus discussion ICCs over 4
      years were 0.18, 0.34, 0.38, 0.75, respectively, showing sustained improvement
      with each consensus discussion. The greatest improvement in reliability of AK
      counts was shown during the first year of consensus discussions, when the ICC
      improved from 0.18 to 0.67. There was no improvement by the fourth year of
      consensus discussion, with pre- and post-consensus ICCs of 0.75 and 0.75,
      respectively. CONCLUSIONS: Annual consensus discussions can lead to improvement
      in reliability of AK counts. This improvement was sustained over 4 years. By the
      fourth year, the discussion meeting had no effect on improvement in reliability.
      A consensus meeting discussion may be helpful for improving reliability in other
      trials.

PMID- 24102421
TI  - Parathyroidectomy improves cardiovascular outcome in nondiabetic dialysis
      patients with secondary hyperparathyroidism.
AB  - OBJECTIVE: Secondary hyperparathyroidism and its associated abnormalities in
      mineral metabolism and haemodynamic changes increase the cardiovascular risk in
      patients with end-stage renal disease (ESRD). Our objective was to determine the
      association of parathyroidectomy (PTX) with major cardiovascular events in
      nondiabetic dialysis patients with severe secondary hyperparathyroidism (SHPTH).
      DESIGN AND PATIENTS: We performed a cohort study with fifty-three nondiabetic
      ESRD patients who were treated with maintenance haemodialysis and who had intact
      parathyroid hormone (PTH) levels > 800 pg/ml. Participants received either only
      medical therapy or medical therapy and total PTX with autotransplantation for
      SHPTH. MEASUREMENTS: We evaluated the associations between PTX and major
      cardiovascular events including death, cerebrovascular accident and myocardial
      infarction. The biochemical and haemodynamic changes associated with PTX were
      measured. RESULTS: During the mean follow-up of 72 months, twenty-three patients
      received only medical treatment (medical group) while thirty patients underwent
      PTX in addition to medical treatment (PTX group). The two groups were comparable
      in respect of baseline characteristics. PTX group was found to be associated with
      a reduced incidence of major cardiovascular events (P = 0.021). A multiple Cox
      regression analysis showed that the variable significantly associated with major
      cardiovascular events was treatment modality (medical therapy vs medical therapy
      and parathyroidectomy, hazard ratio = 26.12, 95% CI = 1.30-526.27, P = 0.033).
      Blood pressure, haemoglobin, alkaline phosphatase, calcium, phosphate and calcium
      * phosphate product significantly improved after PTX. CONCLUSIONS: PTX was
      associated with better cardiovascular outcome in nondiabetic dialysis patients
      with severe SHPTH.

PMID- 24102423
TI  - Does regular exercise in pregnancy influence duration of labor? A secondary
      analysis of a randomized controlled trial.
AB  - OBJECTIVES: To study effects of regular physical exercise in pregnancy on
      duration of the active phase of labor and the proportions of women with prolonged
      active second stage. DESIGN: A two-armed, two-center randomized controlled trial.
      SETTING: St. Olavs Hospital, Trondheim University Hospital and Stavanger
      University Hospital. POPULATION: A total of 855 women were randomized to
      intervention or control groups. METHODS: The intervention was a 12-week exercise
      program, including aerobic and strengthening exercises, conducted between the
      20th and 36th week of gestation. One weekly group session was led by
      physiotherapists and home exercises were encouraged twice a week. Controls
      received standard antenatal care. MAIN OUTCOME MEASURES: The duration of active
      phase of labor and number of prolonged second stage deliveries (active pushing >
      60 min). We also studied labor outcomes. Supplementary analyses were done in a
      subgroup of nulliparous women with a singleton cephalic fetus and spontaneous
      start of term delivery. RESULTS: Duration of labor was similar in the two groups,
      and there were no differences in labor outcomes. In a subgroup analysis the
      duration of active second stage labor was shorter in the control group (p =
      0.01). CONCLUSIONS: Regular physical exercise during pregnancy did not influence
      duration of the active phase of labor or the proportion of women with prolonged
      active second stage.

PMID- 24102422
TI  - Is a baccalaureate in nursing worth it? The return to education, 2000-2008.
AB  - OBJECTIVE: A registered nurse (RN) license can be obtained by completing a
      baccalaureate degree (BSN), an associate degree (AD), or a diploma program. The
      aim of this article is to examine the return to baccalaureate education from the
      perspective of the nurse. DATA SOURCES: National Sample Survey of Registered
      Nurses, 2000, 2004, and 2008. STUDY DESIGN: The effect of education on RN wages
      is estimated using multivariate regression, both for initial education and for
      completing a second degree. The coefficients are used to calculate lifetime
      expected earnings. Multinomial logistic regression is used to examine the
      relationship between education and job title. PRINCIPAL FINDINGS: Lifetime
      earnings for nurses whose initial education is the BSN are higher than those of
      AD nurses only if the AD program requires 3 years and the discount rate is 2
      percent. For individuals who enter nursing with an AD, lifetime earnings are
      higher if they complete a BSN. The BSN is associated with higher likelihood of
      being an advanced practice registered nurse, having an academic title, and having
      a management title. CONCLUSIONS: Because baccalaureate education confers benefits
      both for RNs and their patients, policies to encourage the pursuit of BSN degrees
      need to be supported.

PMID- 24102424
TI  - Usefulness of mean platelet volume as a biomarker for long-term clinical outcomes
      after percutaneous coronary intervention in Korean cohort: a comparable and
      additive predictive value to high-sensitivity cardiac troponin T and N-terminal
      pro-B type natriuretic peptide.
AB  - The aim of this study was to determine the associations of the mean platelet
      volume (MPV) high-sensitivity cardiac troponin T (hs-cTnT) and N-terminal pro-B
      type natriuretic peptide (NT-proBNP) with the development of adverse outcomes
      after percutaneous coronary intervention (PCI). MPV hs-cTnT and NT-proBNP were
      analyzed in 372 patients who underwent PCI. The primary endpoint was cardiac
      death. The secondary endpoint analyzed was cardiovascular events (CVE): the
      composite of cardiac death, myocardial infarction (MI), target vessel
      revascularization (TVR), ischemic stroke and stent thrombosis (ST). The median
      MPV hs-cTnT and NT-proBNP levels were 8.20 (IQR 7.70-8.70) fL, 0.291 (IQR 0.015
      3.785) ng/mL, and 105.25 (IQR 50.84-1128.5) pg/mL, respectively. There were 21
      events of cardiac death, 10 MI (including 4 events of ST), 7 ischemic strokes and
      29 TVR during a mean of 25.8 months of follow-up. The Kaplan-Meier analysis
      revealed that the higher MPV group (>8.20 fL, median) had a significantly higher
      cardiac death rate than the lower MPV group (<=8.20 fL; 9.4% vs. 2.1%, log-rank:
      p = 0.0026). When the MPV cut-off level was set to 8.20 fL using the receiver
      operating characteristic curve, the sensitivity was 81% and the specificity was
      53.3% for differentiating between the group with cardiac death and the group
      without cardiac death. This value was more useful in patients with myocardial
      injury (hs-cTnT >= 0.1 ng/mL) or heart failure (NT-proBNP >= 450 pg/mL). The
      results of this study show that MPV is a predictive marker for cardiac death
      after PCI; its predictive power for cardiac death is more useful in patients with
      myocardial injury or heart failure.

PMID- 24102426
TI  - Antiplatelet-derived growth factor (PDGF) activity in the saliva of ixodid ticks
      is linked with their long mouthparts.
AB  - The saliva of blood-feeding arthropods modulates their vertebrate hosts'
      haemostatic, inflammatory and immune responses to facilitate blood feeding. In a
      previous study, we showed that salivary gland products from ixodid tick species
      also manipulate the wound-healing response by targeting at least four different
      mammalian growth factors: transforming growth factor beta1, hepatocyte growth
      factor, fibroblast growth factor 2 and platelet-derived growth factor (PDGF). In
      addition, species that showed PDGF-binding activity also inhibited cell
      proliferation in vitro and induced changes in cell morphology accompanied by
      disruption of the actin cytoskeleton. Here, we show a correlation between the
      length of the tick hypostome, the sclerotized feeding tube of the mouthparts
      inserted into the host's skin and anti-PDGF activity. This apparent link between
      hypostome length, and hence the potential depth of skin damage, and PDGF-binding
      activity was not apparent for the other growth factors or for other cytokines
      important in wound healing (keratinocyte growth factor, interleukin 6 and stromal
      cell-derived factor 1). However, PDGF-binding activity was no longer correlated
      with anti-cell activities, indicating that an additional as yet unidentified
      activity in tick saliva may affect cellular changes in wound repair. 

PMID- 24102427
TI  - Palladium-catalyzed direct alkenylation of 2-oxazolones: an entry to 3,4,5
      trisubstituted 2-oxazolones.
AB  - Described herein is a novel method for the synthesis of 3,4,5-trisubstituted 2
      oxazolones featuring the first Pd-catalyzed dehydrogenative alkenylation of 2
      oxazolones, which is realized by employing 10 mol % of Pd(OAc)2 as the catalyst
      and the use of readily available Cu(OAc)2 as the oxidant. A wide range of
      functional groups, such as F, Cl, Br, OMe, ester, ketone, amide, alkyl, and aryl
      substituents, are found to be compatible under the reaction conditions. The
      utilization of the C-H functionalization strategy provides a straightforward,
      convenient, and highly atom-economical approach for the construction of 3,4,5
      trisubstituted 2-oxazolones. It is worth noting that the 4-alkenyl 2-oxazolones
      can be smoothly converted into naphtho[1,2-d]oxazol-2-ones via a photochemical
      transformation. 

PMID- 24102425
TI  - Requirement for safety monitoring for approved multiple sclerosis therapies: an
      overview.
AB  - During the last two decades, treatment options for patients with multiple
      sclerosis (MS) have broadened tremendously. All agents that are currently
      approved for clinical use have potential side effects, and a careful risk-benefit
      evaluation is part of a decision algorithm to identify the optimal treatment
      choice for an individual patient. Whereas glatiramer acetate and interferon beta
      preparations have been used in MS for decades and have a proven safety record,
      more recently approved drugs appear to be more effective, but potential risks
      might be more severe. The potential complications of some novel therapies might
      not even have been identified to their full extent. This review is aimed at the
      clinical neurologist in that it offers insights into potential adverse events of
      each of the approved MS therapeutics: interferon beta, glatiramer acetate,
      mitoxantrone, natalizumab, fingolimod and teriflunomide, as well as recently
      approved therapeutics such as dimethyl fumarate and alemtuzumab. It also provides
      recommendations for monitoring the different drugs during therapy in order to
      avoid common side effects. 

PMID- 24102428
TI  - Serum angiopoietin-2 and CRP levels during COPD exacerbations.
AB  - BACKGROUND AND OBJECTIVE: Angiopoietin-2 (Ang-2) is an important mediator of
      angiogenesis and has been implicated in many inflammatory diseases. COPD is
      characterized by systemic inflammation, which is enhanced during exacerbations
      and may be assessed by measuring serum C-reactive protein (CRP). The aim of the
      study was to evaluate serum CRP and Ang-2 levels on the first (D1) and seventh
      day (D7) of hospitalization due to a COPD exacerbation and to examine possible
      associations of CRP and Ang-2 levels and kinetics with the length of hospital
      stay and outcome. METHODS: We conducted a prospective study and evaluated 90
      patients admitted to the hospital with a diagnosis of an acute exacerbation of
      COPD. A venous blood sample was obtained from all patients on D1 and D7 of
      hospitalization, for the measurement of Ang-2 and CRP. RESULTS: Serum Ang-2
      levels were significantly higher on D1 compared to D7 during the course of COPD
      exacerbation (p < 0.001). Serum CRP levels were also significantly higher on D1
      compared to D7 (p < 0.001). Serum Ang-2 presented a significant positive
      correlation with CRP levels both on D1 and D7 (r = 0.315 and r = 0.228,
      respectively). Patients with unfavorable outcome had significantly higher Ang-2
      levels both on D1 (p = 0.04) and D7 (p = 0.01). CONCLUSIONS: Serum Ang-2 levels
      are elevated at the onset of COPD exacerbations and are positively associated
      with CRP levels. Ang-2 levels decrease during the course of COPD exacerbations in
      patients with favorable outcome. Serum Ang-2 may serve as a biomarker that could
      predict the outcome of a COPD exacerbation.

PMID- 24102431
TI  - The application of induced pluripotent stem cells for bone regeneration: current
      progress and prospects.
AB  - Loss of healthy bone tissue and dysosteogenesis are still common and significant
      problems in clinics. Cell-based therapy using mesenchymal stem cells (MSCs) has
      been performed in patients for quite some time, but the inherent drawbacks of
      these cells, such as the reductions in proliferation rate and osteogenic
      differentiation potential that occur with aging, greatly limit their further
      application. Moreover, embryonic stem cells (ESCs) have brought new hope to
      osteoregenerative medicine because of their full pluripotent differentiation
      potential and excellent performance in bone regeneration. However, the ethical
      issues involved in destroying human embryos and the immune reactions that occur
      after transplantation are two major stumbling blocks impeding the clinical
      application of ESCs. Instead, induced pluripotent stem cells (iPSCs), which are
      ESC-like pluripotent cells that are reprogrammed from adult somatic cells using
      defined transcription factors, are considered a more promising source of cells
      for regenerative medicine because they present no ethical or immunological
      issues. Here, we summarize the primary technologies for generating iPSCs and the
      biological properties of these cells, review the current advances in iPSC-based
      bone regeneration and, finally, discuss the remaining challenges associated with
      these cells, particularly safety issues and their potential application for
      osteoregenerative medicine. 

PMID- 24102429
TI  - Tumor necrosis factor-alpha enhances RANKL expression in gingival epithelial
      cells via protein kinase A signaling.
AB  - OBJECTIVE AND BACKGROUND: Periodontitis is an inflammatory disorder of the
      supporting tissue of teeth, which is composed of gingival soft tissue, cementum
      covering the tooth root, alveolar bone and periodontal ligament. The receptor
      activator of nuclear factor kappa B ligand (RANKL) is known to be an essential
      factor for osteoclastogenesis. Recent clinical studies indicate that levels of
      RANKL in the gingival crevicular fluid are increased while levels of its decoy
      receptor, osteoprotegerin (OPG), are decreased in patients with periodontitis.
      Although the gingival sulcus is composed of gingival tissue, RANKL and OPG
      expression in gingival epithelial cells is not fully understood. The aim of this
      study is to investigate the expression of RANKL and OPG in gingival tissue and
      which factors regulate RANKL expression in gingival epithelial cells. MATERIAL
      AND METHODS: Reverse transcriptase polymerase chain reaction analysis, western
      blotting and immunohistochemistry were performed to confirm RANKL and OPG
      expression in gingival epithelial cells (GECs) and in gingival tissue.
      Immunostaining was also examined to confirm tumor necrosis factor (TNF)-alpha and
      TNF receptor type 1 (TNFR1) expression in gingival tissue. Ca9-22 cells, a human
      gingival epithelial cell line and human primary GECs were treated with TNF-alpha.
      Ca9-22 cells were treated by antibodies against TNF receptors, an inhibitor and
      an activator of protein kinase A (PKA) signaling and inhibitors of p38, Erk and
      NF-kappaB signaling to examine TNF-alpha-RANKL signaling pathways. RESULTS: RANKL
      mRNA and protein were expressed in GECs. Immunohistochemistry also showed RANKL
      expression in gingival tissue. On the other hand, the reverse transcriptase
      polymerase chain reaction and immunohistochemistry assay showed that GECs did not
      express OPG. In addition, TNF-alpha and TNFR1 proteins were expressed in
      junctional epithelium. TNF-alpha increased RANKL expression in GECs. TNF-alpha
      induced RANKL expression was inhibited by an antibody against TNFR1 and an
      inhibitor of PKA signaling. Surprisingly, forskolin, a PKA activator, increased
      TNF-alpha-induced RANKL expression. CONCLUSION: RANKL, TNF and TNFR1 were
      coexpressed in junctional epithelium of gingival tissue. TNF-alpha induced RANKL
      expression via TNFR1 and PKA signaling in GECs of junctional epithelium.

PMID- 24102432
TI  - Gene therapy briefs.

PMID- 24102433
TI  - Regenerative toxicology: the role of stem cells in the development of chronic
      toxicities.
AB  - INTRODUCTION: Human stem cell lines and their derivatives, as alternatives to the
      use of animal cells or cancer cell lines, have been widely discussed as cellular
      models in predictive toxicology. However, the role of stem cells in the
      development of long-term toxicities and carcinogenesis has not received great
      attention so far, despite growing evidence indicating the relationship of stem
      cell damage to adverse effects later in life. However, testing this in vitro is a
      scientific/technical challenge in particular due to the complex interplay of
      factors existing under physiological conditions. Current major research programs
      in stem cell toxicity are not aiming to demonstrate that stem cells can be
      targeted by toxicants. Therefore, this knowledge gap needs to be addressed in
      additional research activities developing technical solutions and defining
      appropriate experimental designs. AREAS COVERED: The current review describes
      selected examples of the role of stem cells in the development of long-term
      toxicities in the brain, heart or liver and in the development of cancer. EXPERT
      OPINION: The presented examples illustrate the need to analyze the contribution
      of stem cells to chronic toxicity in order to make a final conclusion whether
      stem cell toxicities are an underestimated risk in mechanism-based safety
      assessments. This requires the development of predictive in vitro models allowing
      the assessment of adverse effects to stem cells on chronic toxicity and
      carcinogenicity.

PMID- 24102434
TI  - Advances in copper complexes as anticancer agents.

PMID- 24102435
TI  - Oxidative palladium(II)-catalyzed C-7 alkenylation of indolines.
AB  - A mild procedure for C-7-selective C-H alkenylation of various indolines under
      oxidative palladium(II) catalysis is reported. A fully substituted urea, formed
      by carbamoylation of the indoline nitrogen atom, functions as a directing group.
      Both alpha,beta-unsaturated acceptors and styrenes participate in this direct C-H
      functionalization. With a free NH group at the urea terminus, the nitrogen atom
      subsequently cyclizes in a 1,4-fashion to yield a six-membered ring. 

PMID- 24102436
TI  - Inhibition of cadmium ion uptake in rice (Oryza sativa) cells by a wall-bound
      form of silicon.
AB  - The stresses acting on plants that are alleviated by silicon (Si) range from
      biotic to abiotic stresses, such as heavy metal toxicity. However, the mechanism
      of stress alleviation by Si at the single-cell level is poorly understood. We
      cultivated suspended rice (Oryza sativa) cells and protoplasts and investigated
      them using a combination of plant nutritional and physical techniques including
      inductively coupled plasma mass spectrometry (ICP-MS), the scanning ion-selective
      electrode technique (SIET) and X-ray photoelectron spectroscopy (XPS). We found
      that most Si accumulated in the cell walls in a wall-bound organosilicon
      compound. Total cadmium (Cd) concentrations in protoplasts from Si-accumulating
      (+Si) cells were significantly reduced at moderate concentrations of Cd in the
      culture medium compared with those from Si-limiting (-Si) cells. In situ
      measurement of cellular fluxes of the cadmium ion (Cd(2+) ) in suspension cells
      and root cells of rice exposed to Cd(2+) and/or Si treatments showed that +Si
      cells significantly inhibited the net Cd(2+) influx, compared with that in -Si
      cells. Furthermore, a net negative charge (charge density) within the +Si cell
      walls could be neutralized by an increase in the Cd(2+) concentration in the
      measuring solution. A mechanism of co-deposition of Si and Cd in the cell walls
      via a [Si-wall matrix]Cd co-complexation may explain the inhibition of Cd ion
      uptake, and may offer a plausible explanation for the in vivo detoxification of
      Cd in rice. 

PMID- 24102437
TI  - Minimal change disease in pregnancy.
AB  - BACKGROUND: New onset minimal change disease (MCD) is rare in pregnancy with the
      potential for serious complications including acute kidney injury (AKI). CASE: A
      case of MCD was diagnosed at 19 weeks gestation by renal biopsy. Within one month
      of starting steroids, the patient experienced normalization of renal function and
      resolution of nephrotic syndrome, although hemodialysis was needed as a
      temporizing measure. CONCLUSION: The differential diagnosis for new onset
      proteinuria in pregnancy should include MCD. In selected cases, renal biopsy can
      be used to confirm diagnosis, and when indicated, hemodialysis should be
      instituted while awaiting a response to steroid therapy.

PMID- 24102438
TI  - Statin restores cardiac autonomic response to acute hypoxia in
      hypercholesterolaemia.
AB  - BACKGROUND: Hypercholesterolaemia may alter cardiovascular autonomic function. We
      investigated the autonomic cardiovascular regulation during normoxia and hypoxia
      in familial isolated HC patients with or without statin treatment. MATERIALS AND
      METHODS: Low (LF-RR) and high (HF-RR) components of spectral analysis of RR
      interval and systolic arterial pressure (LF-SAP) were obtained during 5 min of
      normoxia and isocapnic hypoxia (10% O(2) ) in 10 normotensive familial HC
      patients without medication, in seven HC patients after a 12-week treatment
      period with 40 mg of simvastatin (HC + SVT) and in eight matched normal
      volunteers (CO). RESULTS: The HC patients had significant impairment of cardiac
      autonomic modulation parameters compared with CO at normoxia, which was
      maintained or even accentuated during hypoxia; these parameters included lower
      total variance of RR, increased normalized LF-RR, decreased normalized HF-RR,
      increased LF-RR/HF-RR ratio, higher LF-SAP component and reduced alpha index.
      However, the HC + SVT group had a significant improvement in all parameters: the
      LF-RR and LF-SAP decreased (indicating a decrease in cardiac and vascular
      sympathetic activity), the HF-RR increased (indicating an increase in
      parasympathetic activity) and the spontaneous baroreflex sensitivity improved.
      These changes were detected at normoxia and were maintained during hypoxia.
      CONCLUSIONS: Our data are the first to show that isolated HC is characterized by
      an increase in cardiac and vasomotor sympathetic drive, a decrease in cardiac
      vagal modulation and baroreflex impairment during normoxia and hypoxia. In
      addition, our data suggest that statin treatment has a potential role in
      restoring the physiological cardiovascular autonomic control at baseline and
      during cardiovascular challenge.

PMID- 24102439
TI  - Barriers of delivering oral health care to older people experienced by dentists:
      a systematic literature review.
AB  - OBJECTIVE: To identify barriers of delivering oral health care to older people
      experienced by dentists. METHODS: A comprehensive literature search was carried
      out for studies published in the period January 1990-December 2011, using free
      text and MESH term search strategies for PubMed (Medline), EMBASE and CINAHL.
      RESULTS: The initial search identified 236 potentially relevant publications:
      PubMed (Medline; n = 127), EMBASE (n = 108) and CINAHL (n = 1). After screening
      of titles and abstracts, 14 publications were revealed as relevant for further
      review. Seven articles, focusing on dentists delivering oral health care to older
      people in care homes, were suitable for this review, and seven articles did not
      meet the previously determined quality criteria. One of these articles also
      focused on barriers experienced by dentists working in their own practice and
      delivering oral health care to community-dwelling older people. CONCLUSIONS: The
      most common barriers of delivering oral health care to older people were
      identified respectively as: the lack of adequate equipment in a care home and no
      area for treatment available (n = 4) and the lack of adequate reimbursement for
      working in a care home (n = 5). In addition, the inadequate training and
      experience in delivering oral health care to older care home residents (n = 2)
      were mentioned. Four publications indicated the loss of time from private
      practice as a barrier to deliver oral health care in a care home. We suggest that
      additional research should be initiated to investigate more in detail the
      barriers dentists experience in delivering oral health care to older people in
      their own dental practices.

PMID- 24102440
TI  - Moderation of effects of AAC based on setting and types of aided AAC on outcome
      variables: an aggregate study of single-case research with individuals with ASD.
AB  - OBJECTIVE: The purpose of this meta-analysis was to evaluate the potential
      moderating effects of intervention setting and type of aided augmentative and
      alternative communication (AAC) on outcome variables for students with autism
      spectrum disorders. METHODS: Improvement rate difference, an effect size measure,
      was used to calculate aggregate effects across 35 single-case research studies.
      RESULTS: Results indicated that the largest effects for aided AAC were observed
      in general education settings. With respect to communication outcomes, both
      speech generating devices (SGDs) and the Picture Exchange Communication System
      (PECS) were associated with larger effects than other picture-based systems. With
      respect to challenging behaviour outcomes, SGDs produced larger effects than
      PECS. CONCLUSION: This aggregate study highlights the importance of considering
      intervention setting, choice of AAC system and target outcomes when designing and
      planning an aided AAC intervention.

PMID- 24102441
TI  - The effect of retinal defocus on simple eye-hand and eye-foot reaction time in
      traumatic brain injury (TBI).
AB  - PRIMARY OBJECTIVE: The purpose of the experiment was to assess the effect of
      retinal defocus on simple eye-hand (E-H) and eye-foot (E-F) reaction time (RT) in
      traumatic brain injury (TBI). DESIGN AND METHODS: Sixteen subjects with traumatic
      brain injury (five males and 11 females; aged 22-34 years) participated in the
      experiment. These were compared with 16 visually-normal, age/gender-match
      subjects. Retinal defocus was introduced optically (plano, +1, +2, +3, +4, +10D
      and +2D * 90) in the spectacle plane with binocular viewing. E-H and E-F RT were
      assessed binocularly using the RT-2S Simple Reaction Time Tester (Advanced
      Therapy Products, Glen Allen, VA). The test target colour and angular subtense
      simulated a conventional red/green traffic signal at 120 feet. RESULTS: There was
      no significant effect (p > 0.05) of retinal defocus on either E-H or E-F RT in
      each population. There was a significant effect (p < 0.05) of TBI on both E-H and
      E-F RT as compared with the normative data, with it being longer and more
      variable in TBI. Each RT condition was longest in those with moderate TBI.
      CONCLUSIONS: Both RTs were robust to retinal defocus, thus suggesting central
      nervous system insensitivity for this simple RT task. However, the increased RTs
      and related variability found in TBI, especially in moderate TBI, have potential
      safety implications (e.g. driving a car, ambulating).

PMID- 24102442
TI  - Level of lactate in amniotic fluid and its relation to the use of oxytocin and
      adverse neonatal outcome.
AB  - OBJECTIVE: To assess whether the frequency of adverse neonatal outcome at
      delivery is related to the level of lactate in amniotic fluid and to the use of
      oxytocin. DESIGN: Prospective observational study. SETTING: Soder Hospital,
      Stockholm, Sweden. POPULATION: Seventy-four women in active labor with a
      gestational age >=36 weeks and mixed parity. METHODS: Levels of lactate in
      amniotic fluid were analyzed bedside from an intrauterine catheter every 30 min
      during labor. Deliveries were divided into groups with and without oxytocin. MAIN
      OUTCOME MEASURES: The frequency of adverse neonatal outcome at delivery. RESULT:
      Of the deliveries 13.5% (10/74) concluded with an adverse neonatal outcome. The
      levels of lactate in amniotic fluid increased during labor, more so in deliveries
      where oxytocin was used. In the group with an adverse neonatal outcome, the level
      of lactate in amniotic fluid was significantly higher in the final sample before
      delivery (p = 0.04). In 18 deliveries, stimulation with oxytocin was temporarily
      halted for at least 30 min due to overly stimulated labor contractions. A
      decreasing level of lactate in amniotic fluid was shown within a median 5%/30
      min. In the group where the administration of oxytocin was halted, there was no
      adverse neonatal outcome. CONCLUSION: The frequency of adverse neonatal outcome
      was associated with the level of lactate in amniotic fluid and with the use of
      oxytocin. The level of lactate in amniotic fluid may be an additional valuable
      tool when oxytocin is administered during labor.

PMID- 24102443
TI  - Enrichment of functional properties of ice cream with pomegranate by-products.
AB  - Pomegranate peel rich in phenolics, and pomegranate seed which contain a
      conjugated fatty acid namely punicic acid in lipid fraction remain as by-products
      after processing the fruit into juice. Ice cream is poor in polyunsaturated fatty
      acids and phenolics, therefore, this study was conducted to improve the
      functional properties of ice cream by incorporating pomegranate peel phenolics
      and pomegranate seed oil. Incorporation of the peel phenolics into ice cream at
      the levels of 0.1% and 0.4% (w/w) resulted in significant changes in the pH,
      total acidity, and color of the samples. The most prominent outcomes of phenolic
      incorporation were sharp improvements in antioxidant and antidiabetic activities
      as well as the phenolic content of ice creams. Replacement of pomegranate seed
      oil by milk fat at the levels of 2.0% and 4.0% (w/w) increased the conjugated
      fatty acid content. However, perception of oxidized flavor increased with the
      additional seed oil. When one considers the functional and nutritional
      improvements in the enrichment of the ice cream together with overall
      acceptability results of the sensory analysis, then it follows from this study
      that ice creams enriched with pomegranate peel phenolics up to 0.4% (w/w) and
      pomegranate seed oil up to 2.0% (w/w) could be introduced to markets as
      functional ice cream. Enrichment of ice creams with pomegranate by-products might
      provide consumers health benefits with striking functional properties of
      punicalagins in pomegranate peel, and punicic acid in pomegranate seed oil. 

PMID- 24102444
TI  - Prognostic factors in pemphigus vulgaris and pemphigus foliaceus.
AB  - BACKGROUND: Pemphigus typically has a chronic course, although there is great
      variability in disease duration (DD) and time taken to disease remission (DR)
      between individuals with the disease. The reasons for this are unclear.
      OBJECTIVES: To explore the prognostic influence of epidemiological, clinical,
      immunological and genetic factors on disease course and remission in pemphigus
      vulgaris (PV) and pemphigus foliaceus (PF). METHODS: This was a retrospective
      study of patients with PV and PF, recruited from a single UK centre. Direct and
      indirect immunofluorescence and enzyme-linked immunosorbent assay studies for
      antidesmoglein (Dsg) antibodies were used to assess immunological factors.
      Polymerase chain reaction with sequence specific primers (PCR-SSP) was used to
      assess the Class II human leukocyte antigen status of patients. Prognostic
      endpoints investigated were time to initial first DR and total DD. RESULTS:
      Ninety-five patients were recruited (79 PV and 16 PF). Patients of Indo-Asian
      origin were significantly associated with longer DD than White-British patients
      (P = 0.029). In addition, younger age at onset was associated with a worse
      prognosis in terms of DD: the mean age at presentation of patients with DD of < 5
      years was 49 years (SEM = 3.4) compared with 40 years (SEM = 1.9) in those with
      DD > 5 years (P = 0.039). A higher initial intercellular antibody titre on normal
      human skin substrate was associated with a greater time to initial DR (P = 0.007)
      and high anti-Dsg 3 levels at baseline were associated with a longer total DD (P
      = 0.03). CONCLUSIONS: Ethnic group, age at presentation, initial intercellular
      antibody titre and initial Dsg 3 antibody levels all had a significant impact on
      prognosis of pemphigus.

PMID- 24102445
TI  - The end of hospital cost shifting and the quest for hospital productivity.

PMID- 24102446
TI  - Evaluating troponin C from Psoroptes cuniculi as a diagnostic antigen for a dot
      ELISA assay to diagnose mite infestations in rabbits.
AB  - The mite Psoroptes cuniculi is globally widespread and has a serious impact on
      commercial rabbit breeding. In China, diagnosis of P. cuniculi is currently based
      on conventional clinical methods that entail numerous disadvantages, including
      their failure to diagnose subclinical infections. Hence, alternative measures are
      required, and dot-ELISA is one of the most promising strategies. We cloned and
      expressed the recombinant P. cuniculi troponin C gene for use as a basis for
      novel dot-ELISA assay to detect P. cuniculi infections in rabbits. This amplified
      sequence encoded a 153 amino acid protein of 17.6 kDa and theoretical pI 4.18
      without signal peptide. The recombinant troponin C of P. cuniculi is an outer
      membrane protein and may also be a new P. cuniculi allergen. Results of dot-ELISA
      test showed that this novel assay had more than 90% sensitivity but low
      specificity in distinguishing infections with P. cuniculi or Sarcoptic scabiei,
      despite very high agreement between observers (97-99%; kappa values ranged from
      0.95 to 0.98 for inter- and intra-observer variability test). This study showed
      that this novel method, at present, lacks diagnostic utility. Therefore, although
      simple serological assays such as dot-ELISA show great promise as diagnostic
      tools, we suggest that troponin C is not a suitable diagnostic antigen candidate.

PMID- 24102447
TI  - Intrapulmonary rFVIIa for life threatening pulmonary hemorrhage in a case of
      relapsing acute lymphoblastic leukemia and platelet refractoriness.
AB  - Platelet refractoriness may lead to life-threatening gastro-intestinal,
      intracranial or pulmonary hemorrhage that is difficult to control despite massive
      platelet and red cell transfusion, antifibrinolytic agents, high dose
      corticosteroids, immunoglobulin and intravenous (I.V.) recombinant activated
      factor VII (rFVIIa). In cases with pulmonary hemorrhage, intrapulmonary
      administration of rFVIIa may be more effective in non-responsive cases. We report
      a 51-year-old man with relapsing acute lymphoblastic leukemia (ALL) and platelet
      refractoriness, who suffered a life-threatening pulmonary hemorrhage that was
      refractory to massive platelet transfusion, tranexamic acid, high dose
      corticosteroids, immunoglobulin and intravenous rFVIIa, but responded immediately
      to a single intrapulmonary dose of rFVIIa that was inhaled with a jet nebulizer
      assistance through the endotracheal tube.

PMID- 24102448
TI  - An interpersonal approach to religiousness and spirituality: implications for
      health and well-being.
AB  - The interpersonal tradition (Horowitz & Strack, 2011) provides a rich conceptual
      and methodological framework for theory-driven research on mechanisms linking
      religiousness and spirituality (R/S) with health and well-being. In three
      studies, we illustrate this approach to R/S. In Studies 1 and 2, undergraduates
      completed various self-report measures of R/S, interpersonal style, and other
      aspects of interpersonal functioning. In Study 3, a community sample completed a
      wide variety of R/S measures and a measure of interpersonal style. Many, but not
      all, aspects of religiousness (e.g., overall religiousness, intrinsic
      religiousness) were associated with a warm interpersonal style, and most aspects
      and measures of spirituality were associated with a warm and somewhat dominant
      style. Spirituality and related constructs (i.e., gratitude, compassion) were
      associated with interpersonal goals that emphasize positive relationships with
      others, and with beneficial interpersonal outcomes (i.e., higher social support,
      less loneliness, and less conflict). However, some aspects of R/S (e.g.,
      extrinsic religiousness, belief in a punishing God) were associated with a
      hostile interpersonal style. R/S have interpersonal correlates that may enhance
      or undermine health and emotional adjustment. This interpersonal perspective
      could help clarify why some aspects of religiousness and spirituality are
      beneficial and others are not. 

PMID- 24102450
TI  - Systematic evaluation of 2,6-linked pyridine-thiophene oligomers.
AB  - An efficient synthesis of alternating 2,6-linked pyridine-thiophene (Py-Th)
      oligomers allows systematic evaluation of their optical and electrochemical
      properties. The six- and eight-ring oligomers are revealed to be brightly
      luminescent, even in the solid state. The oligomers are easily reduced but cannot
      be electrochemically oxidized. The longer oligomers have reduction potentials
      similar to those reported for pyridine-thiophene polymers of less defined
      structure. Protonation of the pyridine or substitution at C4 are shown to further
      modulate the electronic properties and, in combination with the low-lying
      absolute LUMO energies, these data suggest that the compounds are potential n
      type materials worthy of further study. 

PMID- 24102452
TI  - Ultrafast shock initiation of exothermic chemistry in hydrogen peroxide.
AB  - We report observations of shock compressed, unreacted hydrogen peroxide at
      pressures up to the von Neumann pressure for a steady detonation wave, using
      ultrafast laser-driven shock wave methods. At higher laser drive energy we find
      evidence of exothermic chemical reactivity occurring in less than 100 ps after
      the arrival of the shock wave in the sample. The results are consistent with our
      MD simulations and analysis and suggest that reactivity in hydrogen peroxide is
      initiated on a sub-100 ps time scale under conditions found just subsequent to
      the lead shock in a steady detonation wave. 

PMID- 24102451
TI  - A novel method for three-dimensional culture of central nervous system neurons.
AB  - Neuronal signal transduction and communication in vivo is based on highly complex
      and dynamic networks among neurons expanding in a three-dimensional (3D) manner.
      Studies of cell-cell communication, synaptogenesis, and neural network plasticity
      constitute major research areas for understanding the involvement of neurons in
      neurodegenerative diseases, such as Huntington's, Alzheimer's, and Parkinson's
      disease, and in regenerative neural plasticity responses in situations, such as
      neurotrauma or stroke. Various cell culture systems constitute important
      experimental platforms to study neuronal functions in health and disease. A major
      downside of the existing cell culture systems is that the alienating planar cell
      environment leads to aberrant cell-cell contacts and network formation and
      increased reactivity of cell culture-contaminating glial cells. To mimic a
      suitable 3D environment for the growth and investigation of neuronal networks in
      vitro has posed an insurmountable challenge. Here, we report the development of a
      novel electrospun, polyurethane nanofiber-based 3D cell culture system for the in
      vitro support of neuronal networks, in which neurons can grow freely in all
      directions and form network structures more complex than any culture system has
      so far been able to support. In this 3D system, neurons extend processes from
      their cell bodies as a function of the nanofiber diameter. The nanofiber scaffold
      also minimizes the reactive state of contaminating glial cells. 

PMID- 24102453
TI  - Effects of natural hybrid and non-hybrid Epichloe endophytes on the response of
      Hordelymus europaeus to drought stress.
AB  - Interspecific hybrid endophytes of the genus Epichloe (Ascomycota,
      Clavicipitaceae) are prevalent in wild grass populations, possibly because of
      their larger gene variation, resulting in increased fitness benefits for host
      plants; however, the reasons are not yet known. We tested hypotheses regarding
      niche expansion mediated by hybrid endophytes, population-dependent interactions
      and local co-adaptation in the woodland grass Hordelymus europaeus, which
      naturally hosts both hybrid and non-hybrid endophyte taxa. Seedlings derived from
      seeds of four grass populations made endophyte free were re-inoculated with
      hybrid or non-hybrid endophyte strains, or left endophyte free. Plants were grown
      in the glasshouse with or without drought treatment. Endophyte infection
      increased plant biomass and tiller production by 10-15% in both treatments.
      Endophyte types had similar effects on growth, but opposite effects on
      reproduction: non-hybrid endophytes increased seed production, whereas hybrid
      endophytes reduced or prevented it completely. The results are consistent with
      the observation that non-hybrid endophytes in H. europaeus prevail at dry sites,
      but cannot explain the prevalence of hybrid endophytes. Thus, our results do not
      support the hypothesis of niche expansion of hybrid-infected plants. Moreover,
      plants inoculated with native relative to foreign endophytes yielded higher
      infections, but both showed similar growth and survival, suggesting weak co
      adaptation.

PMID- 24102454
TI  - 'A terrible dream'--case of idiopathic pituitary insufficiency presenting as
      prolonged delirium in a rural hospital.
AB  - CONTEXT: A 75-year-old female presented to a rural hospital with prolonged
      delirium, and the diagnosis was idiopathic pituitary insufficiency. ISSUE:
      Delirium is a common medical presentation but diagnostic pathways can be
      challenging in rural practice. LESSONS LEARNED: Delirium can be reversible if a
      treatable aetiology is detected.

PMID- 24102455
TI  - Disentangling the effects of geographic and ecological isolation on genetic
      differentiation.
AB  - Populations can be genetically isolated both by geographic distance and by
      differences in their ecology or environment that decrease the rate of successful
      migration. Empirical studies often seek to investigate the relationship between
      genetic differentiation and some ecological variable(s) while accounting for
      geographic distance, but common approaches to this problem (such as the partial
      Mantel test) have a number of drawbacks. In this article, we present a Bayesian
      method that enables users to quantify the relative contributions of geographic
      distance and ecological distance to genetic differentiation between sampled
      populations or individuals. We model the allele frequencies in a set of
      populations at a set of unlinked loci as spatially correlated Gaussian processes,
      in which the covariance structure is a decreasing function of both geographic and
      ecological distance. Parameters of the model are estimated using a Markov chain
      Monte Carlo algorithm. We call this method Bayesian Estimation of Differentiation
      in Alleles by Spatial Structure and Local Ecology (BEDASSLE), and have
      implemented it in a user-friendly format in the statistical platform R. We
      demonstrate its utility with a simulation study and empirical applications to
      human and teosinte data sets. 

PMID- 24102456
TI  - Systemic tentacles of chronic obstructive pulmonary disease: do we need to
      account for renal damage?

PMID- 24102458
TI  - Melody for the soul.

PMID- 24102457
TI  - Comparison of phenolic metabolism and primary metabolism between green 'Anjou'
      pear and its bud mutation, red 'Anjou'.
AB  - Green 'Anjou' pear and its bud mutation, red 'Anjou' were compared to understand
      their differences in phenolic metabolism and its effect on primary metabolism. In
      the flesh of the two cultivars, no difference was detected in the concentration
      of any phenolic compound, the transcript level of MYB10 or the transcript levels
      or activities of key enzymes involved in anthocyanin synthesis. Compared with
      green 'Anjou', the shaded peel of red 'Anjou' had higher anthocyanin
      concentrations, higher transcript levels of MYB10 and higher activity of UDP
      glucose:flavonoid 3-O-glycosyltransferase (UFGT), suggesting that MYB10 regulates
      UFGT to control anthocyanin synthesis in red 'Anjou' peel. In the sun-exposed
      peel, activities of phenylalanine ammonia lyase, dihydroflavonol reductase,
      flavonol synthase and anthocyanidin synthase as well as UFGT were higher in red
      'Anjou' than in green 'Anjou'. The peel of red 'Anjou' had higher activities of
      sorbitol dehydrogenase, raffinose synthase and sucrose synthase and higher levels
      of raffinose, myo-inositol and starch, indicating that sorbitol metabolism,
      raffinose synthesis and starch synthesis were upregulated in red 'Anjou'. The
      flesh of red 'Anjou' had higher concentrations of glucose, but lower activities
      of ATP-dependent phosphofructokinase, pyruvate kinase and glucose-6-phosphate
      dehydrogenase and lower dark respiration. The peel of red 'Anjou' had higher
      activities of glutaminase, asparagine synthetase and asparaginase, and higher
      concentrations of asparagine, aspartate, alanine, valine, threonine and
      isoleucine. The effects of anthocyanin synthesis on primary metabolism in fruit
      peel are discussed. 

PMID- 24102459
TI  - Herbal administration and interaction of cancer treatment.
AB  - The widespread impact of cancer worldwide and noncurative treatment methods
      despite all developments drive patients towards investigating and using
      nonconventional treatment methods. Herbs, which have an important role in
      complementary and alternative medicine practices, may cause unfavorable results
      when used especially with chemotherapeutics in cancer patients due to the
      substances they contain and due to the properties of some, which still cannot be
      clarified. Further overshadowing the success of the treatments, patients do not
      talk about these issues with their doctors and physicians are unable to
      comprehend these properties of herbs. In this compilation we aimed to clarify the
      concepts of complementary and alternative medicine, to gather the properties of
      important and frequently used herbs, and to increase the awareness of physicians
      on this subject.

PMID- 24102460
TI  - A profile of children with complex chronic conditions at end of life among
      Medicaid beneficiaries: implications for health care reform.
AB  - BACKGROUND: As the United States braces for full implementation of health care
      reform, the eyes of the nation are on Medicaid. The large number of newly
      eligible Medicaid beneficiaries may challenge health care resources and
      ultimately impact quality of care. This is a special concern among current
      Medicaid beneficiaries such as children with complex chronic conditions (CCCs)
      who have significant health care needs, especially at end of life (EOL). Yet, a
      comprehensive profile of these children is lacking. OBJECTIVE: To understand the
      demographic and health characteristics, health care utilization, and expenditures
      among Medicaid children with CCCs at EOL. METHODS: Our study used a retrospective
      cohort design with data from the 2007 and 2008 California Medicaid data files.
      Descriptive statistics were used to profile children in the last year of life.
      RESULTS: We found a diverse group of children who suffered with serious, multiple
      chronic conditions, and who accessed comprehensive, multidisciplinary care. Most
      children had neuromuscular conditions (54%), cardiovascular conditions (46%), and
      cancer (30%). A majority (56%) had multiple CCCs. Children with CCCs received
      comprehensive care including hospital inpatient (67%), primary (82%), ancillary
      (87%), and other acute care services (83%); however, few children utilized
      hospice and home health care services (26%). Significant age differences existed
      among the children. CONCLUSIONS: The current California Medicaid system appears
      to provide comprehensive care for children at EOL. The underutilization of
      hospice and home health services, however, represents an opportunity to improve
      the quality of EOL care while potentially reducing or remaining budget neutral.

PMID- 24102461
TI  - A framework for estimating the adverse health effects of contamination events in
      water distribution systems and its application.
AB  - Intentional or accidental releases of contaminants into a water distribution
      system (WDS) have the potential to cause significant adverse health effects among
      individuals consuming water from the system. A flexible analysis framework is
      presented here for estimating the magnitude of such potential effects and is
      applied using network models for 12 actual WDSs of varying sizes. Upper bounds
      are developed for the magnitude of adverse effects of contamination events in
      WDSs and evaluated using results from the 12 systems. These bounds can be applied
      in cases in which little system-specific information is available. The
      combination of a detailed, network-specific approach and a bounding approach
      allows consequence assessments to be performed for systems for which varying
      amounts of information are available and addresses important needs of individual
      utilities as well as regional or national assessments. The approach used in the
      analysis framework allows contaminant injections at any or all network nodes and
      uses models that (1) account for contaminant transport in the systems, including
      contaminant decay, and (2) provide estimates of ingested contaminant doses for
      the exposed population. The approach can be easily modified as better transport
      or exposure models become available. The methods presented here provide the
      ability to quantify or bound potential adverse effects of contamination events
      for a wide variety of possible contaminants and WDSs, including systems without a
      network model. 

PMID- 24102462
TI  - Intervention strategies for spatial orientation disorders in dementia: a
      selective review.
AB  - PURPOSE: This article provides a brief overview of the intervention strategies
      aimed at reducing spatial orientation disorders in elderly people with dementia.
      METHODS: Eight experimental studies using spatial cues, assistive technology
      programs, reality orientation training, errorless learning technique, and
      backward chaining programs are described. They can be classified into two main
      approaches: restorative and compensatory, depending on whether they rely or not
      on residual learning ability, respectively. RESULTS: A review of the efficacy of
      these intervention strategies is proposed. Results suggest that both compensatory
      and restorative approaches may be valuable in enhancing correct way-finding
      behavior, with various degrees of effectiveness. Some issues concerning (a)
      variability in participants' characteristics and experimental designs and (b)
      practicality of intervention strategies do not permit to draw a definite
      conclusion. CONCLUSIONS: Future research should be aimed at a direct comparison
      between these two strategies, and should incorporate an extensive
      neuropsychological assessment of spatial domain.

PMID- 24102463
TI  - Potentially preventable admissions to New Zealand public hospitals for dental
      care: a 20-year review.
AB  - OBJECTIVE: To describe the prevalence of admissions to New Zealand public
      hospitals for dental care and associated time trends for people of all ages
      during the 20-year period 1990-2009. METHODS: The New Zealand Ministry of Health
      National Minimum Data Set (NMDS), a collection that covers all publicly funded
      hospital discharges, was the primary data source for this study. Data over a 20
      year period from 1 January 1990 to 31 December 2009 were included, and a subset
      of ICD 10 codes (K02-K09 and K12 and K13) were selected to identify potentially
      preventable or ambulatory care sensitive conditions (ACSC) leading to admission
      to hospital. Volumes, proportions and rates of admission are presented to
      describe the patterns of admission to hospital. RESULTS: There were 120,046
      admissions to public hospitals in New Zealand between 1990 and 2009 for which the
      provision of dental care was the primary reason for admission. The rate of
      admission to hospital for dental care increased from 0.92 per 1000 population in
      the period 1990-1994 to 2.15 per 1000 population in 2005-2009. Dental admission
      rates were greatest in the 3- to 4-year-old age group, for Maori and Pacific
      people and for people in the most deprived quintile of the NZDep 2006 index.
      Almost one-third of people aged 18-34 years who were admitted to hospital
      primarily for dental care were acute admissions. CONCLUSION: Both the volume and
      the rate of admission to New Zealand public hospitals for dental care have
      increased over the period of this study. A continued focus on strategies to
      reduce the impact of dental disease, particularly in the early childhood
      population and on ensuring accessible primary dental care for the adult
      population, is required.

PMID- 24102465
TI  - Are you knowledgeable about knowledge translation?

PMID- 24102464
TI  - Differential IFN-gamma production by adult and neonatal blood CD56+ natural
      killer (NK) and NK-like-T cells in response to Trypanosoma cruzi and IL-15.
AB  - Early interferon-gamma (IFN-gamma) release by innate cells is critical to direct
      type 1 immune response able to control intracellular pathogens like Trypanosoma
      cruzi. Although CD56(bright) natural killer (NK) cells are reported to be potent
      early IFN-gamma producers, other CD56(+) cells like CD56(dim) NK cells and NK
      like T cells have recently been shown to also release IFN-gamma. We have here
      studied the contribution of each CD56(+) lymphocyte populations in early IFN
      gamma production in both adults and neonates. On this purpose, we analysed the
      kinetics of IFN-gamma production by RT-PCR, ELISA and flow cytometry from 2 h
      onwards after T. cruzi and IL-15 stimulation and sought for the responding
      CD56(+) cells. CD56(bright) and CD56(dim) CD16(-) NK cells were the more potent
      IFN-gamma early producers in response to IL-15 and parasites in adults and
      neonates. In both age groups, the majority of IFN-gamma producing cells were NK
      cells. However, on the contrary to neonates, CD3(+) CD56(+) NK-like T cells and
      CD3(+) CD56(-) 'classical' T cells also contributed to early IFN-gamma production
      in adults. Altogether, our results support that whereas NK cells responded almost
      similarly in neonates and adults, cord blood innate CD56(+) and CD56(-) T cells
      displayed major quantitative and qualitative defects that could contribute to the
      well-known neonatal immune immaturity. 

PMID- 24102466
TI  - Urban particulate matter induces pro-remodeling factors by airway epithelial
      cells from healthy and asthmatic children.
AB  - CONTEXT: Chronic exposure to ambient particulate matter pollution during
      childhood is associated with decreased lung function growth and increased
      prevalence of reported respiratory symptoms. The role of airway epithelium
      derived factors has not been well determined. OBJECTIVE: To determine if urban
      particulate matter (UPM) stimulates production of vascular endothelial growth
      factor (VEGF) and transforming growth factor-beta2 (TGF-beta2), and gene
      expression of mucin 5AC (MUC5AC) and interleukin-(IL)-8 by primary airway
      epithelial cells (AECs) obtained from carefully phenotyped healthy and atopic
      asthmatic school-aged children. METHODS: Primary AECs from 9 healthy and 14
      asthmatic children were differentiated in air--liquid interface (ALI) culture.
      The apical surface was exposed to UPM suspension or phosphate buffered saline
      (PBS) vehicle control for 96 h. VEGF and TGF-beta2 concentrations in cell media
      at baseline, 48 and 96 h were measured via ELISA. MUC5AC and IL-8 expression by
      AECs at 96 h was measured via quantitative polymerase chain reaction. RESULTS:
      Baseline concentrations of VEGF, but not TGF-beta2, were significantly higher in
      asthmatic versus healthy cultures. UPM stimulated production of VEGF, but not TGF
      beta2, at 48 and 96 h; the magnitude of change was comparable across groups. At
      96 h there was greater MUC5AC and IL-8 expression by UPM exposed compared to PBS
      exposed AECs. CONCLUSIONS: Induction of the pro-remodeling cytokine VEGF may be a
      potential mechanism by which UPM influences lung function growth in children
      irrespective of asthma status. Respiratory morbidity associated with UPM exposure
      in children may be related to increased expression of MUC5AC and IL-8.

PMID- 24102468
TI  - Pulmonary toxicity of printer toner following inhalation and intratracheal
      instillation.
AB  - The pulmonary effects of a finished toner were evaluated in intratracheal
      instillation and inhalation studies, using toners with external additives
      (titanium dioxide nanoparticles and amorphous silica nanoparticles). Rats
      received an intratracheal dose of 1 mg or 2 mg of toner and were sacrificed at 3
      days, 1 week, 1 month, 3 months and 6 months. The toner induced pulmonary
      inflammation, as evidenced by a transient neutrophil response in the low-dose
      groups and persistent neutrophil infiltration in the high-dose groups. There were
      increased concentrations of heme oxygenase-1 (HO-1) as a marker of oxidative
      stress in the bronchoalveolar lavage fluid (BALF) and the lung. In a 90-day
      inhalation study, rats were exposed to well-dispersed toner (mean of MMAD: 3.76
      um). The three mass concentrations of toner were 1, 4 and 16 mg/m(3) for 13
      weeks, and the rats were sacrificed at 6 days and 91 days after the end of the
      exposure period. The low and medium concentrations did not induce neutrophil
      infiltration in the lung of statistical significance, but the high concentration
      did, and, in addition, upon histopathological examination not only showed
      findings of inflammation but also of fibrosis in the lung. Taken together, the
      results of our studies suggest that toners with external additives lead to
      pulmonary inflammation and fibrosis at lung burdens suggest beyond the overload.
      The changes observed in the pulmonary responses in this inhalation study indicate
      that the high concentration (16 mg/m(3)) is an LOAEL and that the medium
      concentration (4 mg/m(3)) is an NOAEL.

PMID- 24102467
TI  - Toxicity of lunar dust assessed in inhalation-exposed rats.
AB  - Humans will again set foot on the moon. The moon is covered by a layer of fine
      dust, which can pose a respiratory hazard. We investigated the pulmonary toxicity
      of lunar dust in rats exposed to 0, 2.1, 6.8, 20.8 and 60.6 mg/m(3) of respirable
      size lunar dust for 4 weeks (6 h/day, 5 days/week); the aerosols in the nose-only
      exposure chambers were generated from a jet-mill ground preparation of a lunar
      soil collected during the Apollo 14 mission. After 4 weeks of exposure to air or
      lunar dust, groups of five rats were euthanized 1 day, 1 week, 4 weeks or 13
      weeks after the last exposure for assessment of pulmonary toxicity. Biomarkers of
      toxicity assessed in bronchoalveolar fluids showed concentration-dependent
      changes; biomarkers that showed treatment effects were total cell and neutrophil
      counts, total protein concentrations and cellular enzymes (lactate dehydrogenase,
      glutamyl transferase and aspartate transaminase). No statistically significant
      differences in these biomarkers were detected between rats exposed to air and
      those exposed to the two low concentrations of lunar dust. Dose-dependent
      histopathology, including inflammation, septal thickening, fibrosis and
      granulomas, in the lung was observed at the two higher exposure concentrations.
      No lesions were detected in rats exposed to <=6.8 mg/m(3). This 4-week exposure
      study in rats showed that 6.8 mg/m(3) was the highest no-observable-adverse
      effect level (NOAEL). These results will be useful for assessing the health risk
      to humans of exposure to lunar dust, establishing human exposure limits and
      guiding the design of dust mitigation systems in lunar landers or habitats.

PMID- 24102469
TI  - Computational fluid dynamics simulations of inhaled nano- and microparticle
      deposition in the rhesus monkey nasal passages.
AB  - Anatomically accurate computational fluid dynamics (CFD) models of the nasal
      passages of an infant (6 months old, 1.3 kg) and adult (7 years old, 11.9 kg)
      rhesus monkey were used to predict nasal deposition of inhaled nano- and
      microparticles. Steady-state, inspiratory airflow simulations were conducted at
      flow rates equal to 100, 200 and 300% of the estimated minute volume for resting
      breathing in each model. Particle transport and deposition simulations were
      conducted using the Lagrangian method to track the motion of inhaled particles.
      Nasal deposition fractions were higher in the infant model than the adult model
      at equivalent physiologic flow rates. Deposition curves collapsed when
      differences in nasal geometry were accounted for by plotting microparticle
      deposition versus the Stokes number and nanoparticle deposition as a function of
      the Schmidt number and diffusion parameter. Particle deposition was also
      quantified on major nasal epithelial types. Maximum olfactory deposition ranged
      from 5 to 14% for 1-2 nm particles in the adult and infant models, depending on
      flow rate. For these particle sizes, deposition on respiratory/transitional
      epithelia ranged from 40 to 50%. Increased deposition was also predicted for
      olfactory and respiratory/transitional epithelia for particle sizes >5 um in the
      infant model and >8 um in the adult model. Semi-empirical curves were developed
      based on the CFD simulation results to allow for simplified calculations of age
      based deposition in the rhesus monkey nasal passages that can be implemented into
      lung dosimetry models.

PMID- 24102470
TI  - Formulation and evaluation of metoclopramide solid lipid nanoparticles for rectal
      suppository.
AB  - OBJECTIVES: The purpose of this study was to formulate and characterize
      metoclopramide solid lipid nanoparticles (MCP-SLNs) and incorporating it into
      suppository bases for treatment of nausea and vomiting, produced with
      chemotherapeutic agents, using one dose per day. METHODS: MCP-SLNs was prepared
      using high shear homogenization (hot homogenization) technique using different
      surfactants (tween 80, poloxamer 407, poloxamer 188 and cremophore) in two
      different concentrations (2.5% and 5%) then solid lipid nanoparticle (SLN), whose
      release percentage above 50%, was incorporated into suppository for treatment of
      nausea and vomiting. The prepared SLN and suppositories were then evaluated and
      characterized. KEY FINDINGS: Formulation of poloxamer 407 with compritol and drug
      (F9) produced highest in-vitro % release (80%). Transmission electron microscopy
      showed that SLN had round and spherical shape in form of solid dispersion or drug
      enriched core. Particle size analysis of SLN showed a size range of 24.99-396.8
      nm. Negative zeta potential proves complete drug entrapment. In-vivo study of MCP
      SLN suppositories produced the same %GE as the market metoclopramide (MCP)
      suppository (Primperan) with sustained release effect. CONCLUSION: MCP-SLN
      suppositories (formula F) can reverse decrease in %GE because of emesis with
      sustained release effect. So it succeeded to be an alternative to MCP
      suppositories with no multiple dosing.

PMID- 24102471
TI  - Inducible nitric oxide synthase as a possible target in hypertension.
AB  - Nitric oxide (NO) is an important vasodilator produced by vascular endothelium.
      Its enzymatic formation is derived from three different synthases: neuronal
      (nNOS), endothelial (eNOS) and inducible (iNOS) synthases. While relatively small
      amounts of NO produced by eNOS are important to cardiovascular homeostasis, high
      NO levels produced associated with iNOS activity may have detrimental
      consequences to the cardiovascular system and contribute to hypertension. In this
      article, we reviewed current literature and found mounting evidence indicating
      that increased iNOS expression and activity contribute to the pathogenesis of
      hypertension and its complications. Excessive amounts of NO produced by iNOS up
      regulation can react with superoxide anions forming peroxynitrite, thereby
      promoting nitrosative stress and endothelial dysfunction. In addition, abnormal
      iNOS activity can up-regulate arginase activity, allowing it to compete with eNOS
      for L-arginine, thereby resulting in reduced NO bioavailability. This may also
      lead to eNOS uncoupling with enhanced production of superoxide anions instead of
      NO. All these alterations mediated by iNOS apparently contribute to hypertension
      and its complications. We also reviewed current evidence showing the effects of
      iNOS inhibitors on different animal models of hypertension. iNOS inhibition
      apparently exerts antihypertensive effects, decreases oxidative and nitrosative
      stress, and improves vascular function. Together, these studies highlight the
      possibility that iNOS is a potential pharmacological target in hypertension. 

PMID- 24102472
TI  - Pathophysiology and pharmacologic treatment of venous thromboembolism.
AB  - Venous thrombosis is a common medical disorder affecting nearly one million
      Americans each year. This review will focus primarily on the formation of venous
      thrombosis as well as current and future treatment options. While the full
      pathophysiology of venous thrombosis is not known, recent evidence points to a
      role for von Willebrand Factor, platelets, and neutrophils in thrombus formation.
      Many laboratory and imaging tests may be used for the diagnosis of venous
      thrombosis (VTE), but risk factor identification and clinical examination should
      not be overlooked as they are vital in assuring accurate treatment and patient
      identification. Historically heparin followed by a vitamin K antagonist has been
      the standard of care for treatment of VTE, but increasing data involving factor
      Xa inhibitors and direct thrombin inhibitors may mean a shift in first-line
      therapy in the very near future. Invasive therapies such as catheter-directed
      thrombolysis have also shown promise in the treatment of venous thrombosis and
      will likely see increased use in the future. 

PMID- 24102473
TI  - Genomic identification of potential targets unique to Candida albicans for the
      discovery of antifungal agents.
AB  - Despite of modern antifungal therapy, the mortality rates of invasive infection
      with human fungal pathogen Candida albicans are up to 40%. Studies suggest that
      drug resistance in the three most common species of human fungal pathogens viz.,
      C. albicans, Aspergillus fumigatus (causing mortality rate up to 90%) and
      Cryptococcus neoformans (causing mortality rate up to 70%) is due to mutations in
      the target enzymes or high expression of drug transporter genes. Drug resistance
      in human fungal pathogens has led to an imperative need for the identification of
      new targets unique to fungal pathogens. In the present study, we have used a
      comparative genomics approach to find out potential target proteins unique to C.
      albicans, an opportunistic fungus responsible for severe infection in immune
      compromised human. Interestingly, many target proteins of existing antifungal
      agents showed orthologs in human cells. To identify unique proteins, we have
      compared proteome of C. albicans [SC5314] i.e., 14,633 total proteins retrieved
      from the RefSeq database of NCBI, USA with proteome of human and non-pathogenic
      yeast Saccharomyces cerevisiae. Results showed that 4,568 proteins were
      identified unique to C. albicans as compared to those of human and later when
      these unique proteins were compared with S. cerevisiae proteome, finally 2,161
      proteins were identified as unique proteins and after removing repeats total
      1,618 unique proteins (42 functionally known, 1,566 hypothetical and 10 unknown)
      were selected as potential antifungal drug targets unique to C. albicans. 

PMID- 24102474
TI  - Modeling preparation condition and composition-activity relationship of
      perovskite-type LaxSr1-xFeyCo1-yO3 nano catalyst.
AB  - In this paper, an artificial neural network (ANN) is first applied to perovskite
      catalyst design. A series of perovskite-type oxides with the LaxSr1-xFeyCo1-yO3
      general formula were prepared with a sol-gel autocombustion method under
      different preparation conditions. A three-layer perceptron neural network was
      used for modeling and optimization of the catalytic combustion of toluene. A high
      R2 value was obtained for training and test sets of data: 0.99 and 0.976,
      respectively. Due to the presence of full active catalysts, there was no
      necessity to use an optimizer algorithm. The optimum catalysts were
      La0.9Sr0.1Fe0.5Co0.5O3 (Tc=700 and 800  degrees C and [citric
      acid/nitrate]=0.750), La0.9Sr0.1Fe0.82Co0.18O3 (Tc=700  degrees C, [citric
      acid/nitrate]=0.750), and La0.8Sr0.2Fe0.66Co0.34O3 (Tc=650  degrees C, [citric
      acid/nitrate]=0.525) exhibiting 100% conversion for toluene. More evaluation of
      the obtained model revealed the relative importance and criticality of
      preparation parameters of optimum catalysts. The structure, morphology,
      reducibility, and specific surface area of catalysts were investigated with XRD,
      SEM, TPR, and BET, respectively.

PMID- 24102475
TI  - Infrared spectral model for subwavelength particles of mixed composition based on
      the spectra of individual particles with calibration data for airborne dust.
AB  - A Mie-Bruggeman spectral model is presented which predicts the orientationally
      averaged, infrared spectra of individual mixed-composition particles or the
      average spectrum of collections of such particles. The model uses parameters
      extracted from sets of individual particle spectra of pure materials known to be
      in subject mixtures. The spectra of both calibrants and subject particles were
      recorded by trapping size-selected particles in the holes of plasmonic metal
      mesh. Calibrating data is presented for quartz, calcite, dolomite, three clays,
      gypsum, polyethylene, and living organic material (yeast cells). The individual
      particle spectra of these calibrants are averaged to account for crystal
      orientation effects, fit by a Mie theory model, and tabulated herein as
      dielectric functions of each component. The component dielectric functions are
      combined in this model with Bruggeman effective medium theory producing a
      spectral prediction for mixed-composition particles. The Mie-Bruggeman model was
      used to analyze the composition of dust from our lab air [K. E. Cilwa et al. J.
      Phys. Chem. C 2011, 115, 16910] based on the average spectrum of the dust
      particles. The model does a reasonable job of characterizing the dust in our
      laboratory air exhibiting promise for future applications. This work presents the
      model and illustrates potential; however, much more work will be required before
      its accuracy as a quantitative analytical method is established. 

PMID- 24102478
TI  - Pharmacokinetic evaluation of desogestrel as a female contraceptive.
AB  - INTRODUCTION: Desogestrel (DSG) is a third-generation 19-nortestosterone
      derivative progestogen. It is contained in many oral contraceptive preparations,
      both combined (COCs) to ethinyl-estradiol (EE) or alone in a progestin-only pill
      (POP). Its principal metabolite (etonogestrel, ETN) is the only progestin used
      for intravaginal combined contraception and one of the most used for subdermal
      hormonal contraception. AREAS COVERED: This is a review of the available data on
      the pharmacokinetics of DSG and ETN in hormonal contraception. The material
      included was searched and obtained via Medline, PubMed, and EMBASE up to July
      2013 using the search terms 'pharmacokinetics, metabolism' in combination with
      'desogestrel, etonogestrel, and progestins.' EXPERT OPINION: DSG and its
      metabolite ETN are very suitable molecules for use in hormonal contraception. For
      the oral use the molecule used is DSG, while for parenteral routes (intravaginal,
      subdermal) its metabolite ETN is the compound of choice. In both cases (oral and
      parenteral) the active molecule in the organism is the latter (ETN), due to the
      rapid in vivo metabolism of oral DSG. The contraceptive efficacy and tolerability
      of all the formulations present on the market (mono/multiphasic EE/DSG COCs, DSG
      POP, EE/ETN vaginal ring, ETN implant) are reassuring, permitting a long-term
      use. The estrogenic component increases the contraindications, forcing the
      prescription to the safer only-progestin preparations, DSG POP or ETN implant.

PMID- 24102479
TI  - Isolation and characterization of alveolar epithelial type II cells derived from
      mouse embryonic stem cells.
AB  - The use of embryonic stem cells (ESCs) to regenerate distal lung epithelia
      damaged by injuries or diseases requires development of safe and efficient
      methodologies that direct ESC differentiation into transplantable distal lung
      epithelial progenitors. Time-consuming culture procedure and low differentiation
      efficiency are major problems that are associated with conventional
      differentiation approaches via embryoid body formation. The use of a growth
      factor cocktail or a lung-specific cell-conditioned medium to enrich definitive
      endoderm for efficient differentiation of mouse ESCs (mESC) into alveolar
      epithelial progenitor type II cells (ATIICs) has been reported, but not yet
      successful for generating a homogenous population of ATIICs for tissue
      regeneration purpose, and it remains unclear whether or not those mESC-derived
      ATIICs possess normal biological functions. Here, we report a novel method using
      a genetically modified mESC line harboring an ATIIC-specific neomycin(R)
      transgene in Rosa 26 locus. We showed that ATIICs can be efficiently
      differentiated from mESCs as early as day 7 by culturing them directly on
      Matrigel-coated plates in DMEM containing 15% knockout serum replacement. With
      this culture condition, the genetically modified mESCs can be selectively
      differentiated into a homogenous population (>99%) of ATIICs. Importantly, the
      mESC-derived ATIICs (mESC-ATIICs) exhibited typical lamellar bodies and expressed
      surfactant protein A, B, and C as normal control ATIICs. When cultured with an
      air-liquid-interface culture system in Small Airway Epithelial Cell Growth
      Medium, the mESC-ATIICs can be induced to secrete surfactant proteins after being
      treated with dibutyryl cAMP+dexamethasone. These mESC-ATIICs can synthesize and
      secrete surfactant lipid in response to secretagogue, demonstrating active
      surfactant metabolism in mESC-ATIICs as that seen in normal control ATIICs. In
      addition, we demonstrated that the selected mESC-ATIICs can be maintained on
      Matrigel-coated plates for at least 4 days with robust proliferative capacity.
      When cultured in DMEM medium containing 10% FBS, mESC-ATIICs spontaneously
      differentiated into alveolar epithelial type I cells. Collectively, these data
      demonstrate that the genetically modified mESCs can be selectively differentiated
      into a homogenous population of functional ATIICs, providing a reliable cell
      source to explore their therapeutic potential in lung tissue regeneration. 

PMID- 24102480
TI  - Acupuncture and acupressure and massage health outcomes for patients with
      anorexia nervosa: findings from a pilot randomized controlled trial and patient
      interviews.
AB  - OBJECTIVES: This study examined the feasibility of conducting a randomized
      controlled trial of acupuncture compared with an active control in an inpatient
      setting, to examine individuals' experience of the interventions, clinical
      outcomes from the trial, and to integrate data to explain the trial findings.
      DESIGN: This was a pilot randomized controlled trial with in-depth interviews
      with trial participants. SETTING: The study was conducted at a private medical
      facility in Sydney, Australia. SUBJECTS: Twenty-six (26) patients with anorexia
      nervosa who were medically stable were the subjects. INTERVENTIONS: Treatment as
      usual was administered, and the intervention was delivered twice a week for the
      first 3 weeks, followed by weekly treatment for three weeks. The acupuncture
      group received acupuncture at the points Hegu (LI4), Zusanli (ST36), Neiguan
      (PC6), Taichong (LR3), Yanglingquan (GB34), and additional points based on the
      Traditional Chinese Medicine diagnosis. The control group received acupressure
      and massage. Acupressure involved consciously and gradually directing pressure to
      the center of the point being worked on. OUTCOME MEASURES: Clinical outcomes were
      measured at baseline and at 6 weeks following completion of the intervention. The
      primary outcome measure was body-mass index (BMI), and secondary outcomes
      included eating disorder psychopathology, anxiety, and depression. A
      semistructured interview was conducted asking questions about their interaction
      with the practitioner, what happened, how they felt, whether it made them feel
      differently, and what they attributed any change to. RESULTS: We found timely
      recruitment with the population recruited within a 5-month period. Study dropouts
      were 23% and treatment compliance was moderate, but acceptable for this
      challenging population. Participants in the control group demonstrated reduced
      eating concerns. Participants described both interventions positively, and
      experienced a sense of calmness and relaxation. CONCLUSIONS: Acupuncture and
      acupressure and massage may improve the patient's subjective sense of wellbeing,
      and further research is needed.

PMID- 24102481
TI  - Matrix-IR spectroscopic investigations of the thermolysis and photolysis of
      diazoamides.
AB  - Matrix photolysis of N,N-dialkyldiazoacetamides 1a-d at 7-10 K results in either
      the formation of C-H insertion products (in case of N,N-dimethyl and N,N-diethyl
      diazoamides) or almost exclusive Wolff rearrangement to ketenes (in the case of
      the cyclic diazoamides N-(diazoacetyl)azetidine and N-(diazoacetyl)pyrrolidine).
      This can be ascribed to higher activation barriers for the approach of the
      singlet carbene p orbital in 5 (or of the diazo carbon in an excited state of 1)
      to the stronger and "tied back" nature of the C-H bonds in the cyclic
      substituents. In contrast, flash vacuum thermolysis (FVT) of diazoamides 1a-d, in
      which reactions of excited states are excluded, gives rise to clean C-H insertion
      with only minor Wolff rearrangement to ketenes. 

PMID- 24102482
TI  - Estimation of urinary concentration of aflatoxin M1 in Chinese pregnant women.
AB  - Aflatoxin M1 (AFM1 ) is a main cause of hepatocarcenogenoma in Chinese
      population. Measurement of aflatoxin exposure in human may help in providing
      clear evidence for the exposure of specific environmental pollutants in certain
      population. "One child policy" in China offered parents more careful to choose
      safe food during pregnancy, but no reports published on the efficacy of their
      endeavor. In present study, we aimed to assess the exposure of AFM1 in Chinese
      pregnant women. The urine samples were collected from 600 volunteers from
      Zhejiang province, China and the urinary concentration of AFM1 was measured using
      ELISA kit. AFM1 was detected in 84% of the pregnant women. The geometric mean and
      95th percentile concentration of AFM1 in pregnant women were 50.3 ng/L and 633.5
      ng/L, respectively. Our results point out that pregnant women especially are at
      the high risk of exposure to AFM1 . Our results also indicate that although "one
      child policy" offered parents to pay more attention for the selection of safe
      food, but detection of AFM1 in urine of pregnant women indicate that more foods
      containing AFM1 still need to be detected. Highest exposure of AFM1 in pregnant
      women indicates that awareness campaigns must be started especially in the rural
      areas of China regarding the possible hazardous effects of AFM1 exposure in
      pregnant women. 

PMID- 24102483
TI  - Recommendations for using msBayes to incorporate uncertainty in selecting an abc
      model prior: a response to oaks et Al.
AB  - Prior specification is an essential component of parameter estimation and model
      comparison in Approximate Bayesian computation (ABC). Oaks et al. present a
      simulation-based power analysis of msBayes and conclude that msBayes has low
      power to detect genuinely random divergence times across taxa, and suggest the
      cause is Lindley's paradox. Although the predictions are similar, we show that
      their findings are more fundamentally explained by insufficient prior sampling
      that arises with poorly chosen wide priors that critically undersample
      nonsimultaneous divergence histories of high likelihood. In a reanalysis of their
      data on Philippine Island vertebrates, we show how this problem can be
      circumvented by expanding upon a previously developed procedure that accommodates
      uncertainty in prior selection using Bayesian model averaging. When these
      procedures are used, msBayes supports recent divergences without support for
      synchronous divergence in the Oaks et al. data and we further present a
      simulation analysis that demonstrates that msBayes can have high power to detect
      asynchronous divergence under narrower priors for divergence time. Our findings
      highlight the need for exploration of plausible parameter space and prior
      sampling efficiency for ABC samplers in high dimensions. We discus potential
      improvements to msBayes and conclude that when used appropriately with model
      averaging, msBayes remains an effective and powerful tool.

PMID- 24102484
TI  - Paediatric patients with abusive head trauma treated in US Emergency Departments,
      2006-2009.
AB  - OBJECTIVE: To study characteristics and outcomes of paediatric patients with
      abusive head trauma (AHT) treated in emergency departments. METHODS: Nationwide
      Emergency Department Sample (NEDS) data were analysed. The CDC recommended AHT
      definition was used to classify children <= 4 years with head trauma into AHT and
      non-AHT groups. Outcomes were compared between patients with AHT and patients
      with non-AHT. Logistic models were fitted to identify risk factors. RESULTS: An
      estimated 10 773 paediatric patients with AHT were treated in EDs in 2006-2009.
      The average annual rate was 12.83 per 100 000 for children <= 4 years. Children <
      1 year of age accounted for most AHT cases (60.6%) and males had a significantly
      higher AHT rate than females. Medicaid was the primary payer for 66.1% of AHT
      injuries and 40.3% of non-AHT injuries. The case mortality rate was 53.9 (95% CI
      = 41.0-66.7) per 1000 patients with AHT compared with 1.6 (95% CI = 1.4-1.9) per
      1000 patients with non-AHT. CONCLUSIONS: Child caregivers should be educated
      about the serious consequences of AHT and proper techniques for caring for
      infants. Unbiased and accurate documentation of AHT by physicians and medical
      coders is crucial for monitoring AHT injuries.

PMID- 24102485
TI  - The Arabidopsis RAD51 paralogs RAD51B, RAD51D and XRCC2 play partially redundant
      roles in somatic DNA repair and gene regulation.
AB  - The eukaryotic RAD51 gene family has seven ancient paralogs conserved between
      plants and animals. Among these, RAD51, DMC1, RAD51C and XRCC3 are important for
      homologous recombination and/or DNA repair, whereas single mutants in RAD51B,
      RAD51D or XRCC2 show normal meiosis, and the lineages they represent diverged
      from each other evolutionarily later than the other four paralogs, suggesting
      possible functional redundancy. The function of Arabidopsis RAD51B, RAD51D and
      XRCC2 genes in mitotic DNA repair and meiosis was analyzed using molecular
      genetic, cytological and transcriptomic approaches. The relevant double and
      triple mutants displayed normal vegetative and reproductive growth. However, the
      triple mutant showed greater sensitivity than single or double mutants to DNA
      damage by bleomycin. RNA-Seq transcriptome analysis supported the idea that the
      triple mutant showed DNA damage similar to that caused by bleomycin. On bleomycin
      treatment, many genes were altered in the wild-type but not in the triple mutant,
      suggesting that the RAD51 paralogs have roles in the regulation of gene
      transcription, providing an explanation for the hypersensitive phenotype of the
      triple mutant to bleomycin. Our results provide strong evidence that Arabidopsis
      XRCC2, RAD51B and RAD51D have complex functions in somatic DNA repair and gene
      regulation, arguing for further studies of these ancient genes that have been
      maintained in both plants and animals during their long evolutionary history. 

PMID- 24102486
TI  - Sucrose induces expression of the sorbitol-6-phosphate dehydrogenase gene in
      source leaves of loquat.
AB  - Rosaceae fruit trees use sorbitol and sucrose as translocating sugars and the
      sorbitol-to-sucrose ratio in source leaves determines apple fruit quality. Here,
      we investigate the effects of sugars on the expression of genes encoding key
      photosynthetic enzymes, including sorbitol-6-phosphate dehydrogenase (S6PDH, EC
      1.1.1.200), sucrose phosphate synthase (SPS, EC 2.4.1.14), and ADP-glucose
      pyrophosphorylase (ADPGPPase, EC 2.7.7.27) to understand the sugar-signaling
      mechanism in Rosaceae fruit trees. Mature leaf-petiole cuttings of loquat
      (Eriobotrya japonica Lindl. cv. Mogi) were supplied with a water, sorbitol or
      sucrose solution for 2 days at 20 degrees C. The relative levels of the
      transcripts were analyzed by real-time polymerase chain reaction (PCR). S6PDH
      transcription was decreased by sorbitol but drastically increased by sucrose. SPS
      and ADPGPPase large subunit transcription were decreased by sucrose and sorbitol.
      The simultaneous application of sorbitol and sucrose revealed that S6PDH
      transcription increased in a dose-dependent manner with sucrose. These results
      show that both sorbitol and sucrose work as signaling molecules in source organs
      of Rosaceae fruit trees. These trees have mechanisms to positively keep sorbitol
      as the dominant translocating sugar, suggesting that sorbitol plays an important
      role in their survival strategy. Effects of various sugars on S6PDH expression
      were investigated. Palatinose, a sucrose analog, increased S6PDH transcription
      much more drastically than sucrose. Mannose and 3-O-methylglucose, glucose
      analogs, also increased S6PDH transcription; however, glucose did not. Models of
      sugar signaling in source organs of Rosaceae fruit trees are discussed. 

PMID- 24102487
TI  - Voices from the past: comparing the rapid prompting method and facilitated
      communication.
AB  - OBJECTIVE: This article briefly reviews the history and damage caused by
      facilitated communication (FC) and highlights the parallels between FC and the
      Rapid Prompting Method (RPM). BACKGROUND: FC involves a therapist (or
      facilitator) supporting the hand of a person with autism while a message is typed
      on a letter board. FC is widely acknowledged to be a pseudoscientific, unsafe,
      and unethical treatment for people with autism. RPM is a more recent intervention
      for people with autism that involves the facilitator holding and moving the
      letter board while the individual with autism moves their own hand. Those who
      espouse the perceived benefits of FC and RPM make strikingly similar claims of
      hidden intelligence and extraordinary communication abilities in people with
      autism following treatment. CONCLUSION: Clients, proponents, and practitioners of
      RPM should demand scientific validation of RPM in order to ensure the safety of
      people with disabilities that are involved with RPM.

PMID- 24102488
TI  - Meta-analysis of pre-miRNA polymorphisms association with susceptibility to
      autoimmune diseases.
AB  - It has been suggested that the rs2910164 and rs3746444 polymorphisms of pre-miRNA
      are significantly associated with the risk of autoimmune diseases (ADs),
      described as candidate susceptibility factors, whereas results have yield
      conflicting findings. We conducted this meta-analysis to investigate whether
      these two polymorphisms contribute to susceptibility to ADs by using allele
      comparison and different genetic models, and we also performed stratified
      analyses by ethnicity and disease phenotype. Our meta-analysis demonstrated that
      increased risk of ADs was significantly associated with GC genotype in Asians for
      SNP rs2910164 in the stratified analyses by ethnicity; there was increased OR for
      GC genotype compared with that for GG+CC genotype in other disease subgroup,
      respectively (OR=0.89, 95% CI=0.79-0.99; OR=0.84, 95% CI=0.75-0.95,
      respectively). Moreover, elevated AD risk was found to be associated with CC
      genotype of rs3746444 in contrast to TT and TT+TC carriers, respectively
      (OR=0.55, 95% CI=0.34-0.90; OR=0.59, 95% CI=0.36-0.97, respectively). Taken
      together, these findings indicated that the rs2910164 and rs3746444 polymorphisms
      may play potential roles in the pathogenesis of ADs.

PMID- 24102489
TI  - Magnetic tuning of plasmonic excitation of gold nanorods.
AB  - By using gold nanorods as an example, we report the dynamic and reversible tuning
      of the plasmonic property of anisotropically shaped colloidal metal
      nanostructures by controlling their orientation using external magnetic fields.
      The magnetic orientational control enables instant and selective excitation of
      the plasmon modes of AuNRs through the manipulation of the field direction
      relative to the directions of incidence and polarization of light. 

PMID- 24102490
TI  - Algorithm for reaction classification.
AB  - Reaction classification has important applications, and many approaches to
      classification have been applied. Our own algorithm tests all maximum common
      substructures (MCS) between all reactant and product molecules in order to find
      an atom mapping containing the minimum chemical distance (MCD). Recent
      publications have concluded that new MCS algorithms need to be compared with
      existing methods in a reproducible environment, preferably on a generalized test
      set, yet the number of test sets available is small, and they are not truly
      representative of the range of reactions that occur in real reaction databases.
      We have designed a challenging test set of reactions and are making it publicly
      available and usable with InfoChem's software or other classification algorithms.
      We supply a representative set of example reactions, grouped into different
      levels of difficulty, from a large number of reaction databases that chemists
      actually encounter in practice, in order to demonstrate the basic requirements
      for a mapping algorithm to detect the reaction centers in a consistent way. We
      invite the scientific community to contribute to the future extension and
      improvement of this data set, to achieve the goal of a common standard. 

PMID- 24102491
TI  - Second thoughts on Agieren: listening to the enacted.
AB  - The author proposes an expanded notion of the concept of Agieren, introduced by
      Freud in his theory of transference, and to this effect discusses three
      metapsychological articulations. Firstly, the idea of the psyche is proposed
      containing different co-existing modalities of representing emotional experience.
      One is a verbal inscription governed by the logic of the dynamically repressed,
      and another is the registration of a mode of being, in the form of sequences of
      psychic gestures that the subject exchanges with his objects. The author proposes
      that the psychic gesture is the ideopictographic representation for certain
      emotional states never verbally thought and, consequently, its metapsychological
      status is unconscious but not repressed. Secondly, these unconscious registers
      contain specific modalities of processing reality, created by the projective
      attribution of the parental unconscious. Finally, by conceiving this model of
      unconscious, ideopictographically represented as psychic gestures, the author
      proposes that a patient's emotional state, becoming a psychic gesture of the
      analytic pair, is enacted within the analytic stage. His proposal departs from
      the frequent view of enactment as a result of the non-represented aspects of the
      psyche. It is assumed that what is played out by the analytic pair pertains to
      the unconscious imaginary represented.

PMID- 24102492
TI  - Novel mutations in typical and atypical genetic loci through exome sequencing in
      autosomal recessive cerebellar ataxia families.
AB  - Nearly a thousand mutations mapping to 60 different loci have been identified in
      cerebellar ataxias. However, almost 50% of the cases remain genetically
      uncharacterized and there is a difference in prevalence as well as in the
      phenotypic spectrum of ataxia among various geographical regions. This poses a
      challenge for setting up a genetic panel for screening ataxia. In our ataxic
      cohort of 1014 families, 61% are genetically uncharacterized (UC). We
      investigated the potential of whole exome sequencing in conjunction with
      homozygosity mapping (HM) to delineate the genetic defects in three
      uncharacterized families with recessive inheritance each manifesting some unusual
      phenotype: (i) infantile onset ataxia with hearing loss (IOAH), (ii) Juvenile
      onset cerebellar ataxia with seizures (JCS) and (iii) Friedreich ataxia-like (FA
      like). We identified a novel missense mutation in c10orf2 in the family with
      IOAH, compound heterozygous mutations in CLN6 in the family with JCS and a
      homozygous frame-shift mutation in SACS in the FA-like patient. Phenotypes
      observed in our families were concordant with reported phenotypes of known
      mutations in the same genes thus obviating the need for functional validation.
      Our study revealed novel variations in three genes, c10orf2, CLN6, and SACS, that
      have so far not been reported in India. This study also demonstrates the utility
      of whole exome screening in clinics for early diagnosis. 

PMID- 24102493
TI  - Feasibility of a new image processing (4D Auto LVQ) to assessing right
      ventricular function in patients with chronic obstructive pulmonary disease.
AB  - A new single-beat three-dimensional (3D) real time echocardiographic semi
      automatic images processing (4D Auto LVQ) allows accurate assessment of left
      ventricular function, but whether it is suitable for the evaluation of right
      ventricular function remains unknown. To evaluate the feasibility of this
      procedure for assessing right ventricular volumes and function, right ventricular
      end-diastolic volumes (RVEDV), end-systolic volumes (RVESV) and ejection fraction
      (RVEF), stroke volumes (SV) and cardiac output (CO) were computed in 49 patients
      with chronic obstructive pulmonary disease (COPD) using 4D Auto LVQ. The
      myocardial performance index (MPI) was obtained by Doppler tissue imaging. The RV
      function parameters were compared with MPI by linear correlation analysis. A
      comparison of the performance of these RV function parameters in discrimination
      between MPI at a value of >0.45 or not was done. Compared with normal subjects,
      patients with COPD had significantly greater RVEDV, RVESV, MPI and significantly
      lower RVEF. Significant correlations were found between RVEF and MPI (r = -0.67,
      p < 0.001). The areas under the receiver operating characteristic curve for RVEF
      in discrimination between MPI at a value of >0.45 or not were 0.72, while they
      were 0.55 for SV and 0.57 for CO, respectively. The overall sensitivity,
      specificity and accuracy for RVEF analysis in predicting a >0.45 MPI in patients
      with COPD was 78.57%, 66.67% and 73.46%, respectively. These data suggest that 4D
      Auto LVQ is a feasible method for right ventricular volumes and function
      quantification in patients with COPD. Further studies are needed to improve the
      accuracy of the measurements.

PMID- 24102494
TI  - Perception of risk and the attribution of responsibility for accidents.
AB  - Accidents, one often hears, "happen"; we accept, and even expect, that they will
      be part of daily life. But in situations in which injury or death result,
      judgments of responsibility become critical. How might our perceptions of risk
      influence the ways in which we allocate responsibility for an accident? Drawing
      from attribution and risk perception theory, this study investigates how
      perceived controllability and desirability of risk, in addition to perceived
      danger and recreational risk-taking, relate to attributions of responsibility for
      the cause of unintentional injury in a unique setting: U.S. national parks. Three
      parks, Mount Rainier, Olympic, and Delaware Water Gap, provide the setting for
      this survey-based study, which considers how park visitors (N = 447) attribute
      responsibility for the cause of a hypothetical visitor accident. Results suggest
      that respondents tended to make more internal (i.e., related to characteristics
      of the victim), rather than external (i.e., related to characteristics of the
      park, or park management) attributions. As respondents viewed park-related risk
      as controllable, they were more likely to attribute the cause of the accident to
      the victim. Moreover, among other significant variables, having experienced a
      similar accident predicted lower internal causal attribution. Opportunities for
      future research linking risk perception and attribution variables, as well as
      practical implications for the management of public outdoor settings, are
      presented. 

PMID- 24102495
TI  - Neutrophils have a protective role during early stages of Leishmania amazonensis
      infection in BALB/c mice.
AB  - Neutrophils are involved in the early stages of immune responses to pathogens.
      Here, we investigated the role of neutrophils during the establishment of
      Leishmania amazonensis infection in BALB/c and C57BL/6 mice. First, we showed an
      accumulation of neutrophils between 6 and 24 h post-infection, followed by a
      reduction in neutrophil numbers after 72 h. Next, we depleted neutrophils prior
      to infection using RB6-8C5 or 1A8 mAb. Neutrophil depletion led to faster lesion
      development, increased parasite numbers and higher arginase activity during the
      first week of infection in BALB/c mice, but not in C57BL/6 mice. Increased
      susceptibility was accompanied by augmented levels of anti-L. amazonensis IgG and
      increased production of IL-10 and IL-17. Because IL-10 is a mediator of
      susceptibility to Leishmania infection, we blocked IL-10 signalling in neutrophil
      depleted mice using anti-IL-10R. Interestingly, inhibition of IL-10 signalling
      abrogated the increase in parasite loads observed in neutrophil-depleted mice,
      suggesting that parasite proliferation is at least partially mediated by IL-10.
      Additionally, we tested the effect of IL-17 in inflammatory macrophages and
      observed that IL-17 increased arginase activity and favoured parasite growth.
      Taken together, our data indicate that neutrophils control parasite numbers and
      limit lesion development during the first week of infection in BALB/c mice. 

PMID- 24102496
TI  - Monocarboxylate transporter mediated uptake of moxifloxacin on human retinal
      pigmented epithelium cells.
AB  - OBJECTIVES: This work was aim to determine in vitro interaction of moxifloxacin
      with monocarboxylate transporter (MCT) using a human retinal pigment epithelium
      cells (ARPE-19). METHODS: In vitro moxifloxacin uptakes were performed at 37
      degrees C across ARPE-19 cells. Concentration-dependent uptake of moxifloxacin
      was performed to delineate moxifloxacin kinetics with MCT. Effects of MCT
      substrates, MCT inhibitors, pH and metabolic inhibitors on moxifloxacin uptake
      were conducted to delineate mechanism of moxifloxacin influx via MCT. KEY
      FINDINGS: Moxifloxacin uptake was found to exhibit saturable kinetics (K(m) =
      1.56 +/- 0.32 MUM and V(max) = 0.58 +/- 0.16 MUM/min/mg protein). Higher uptake
      of moxifloxacin was observed at acidic pH. MCT substrates such as salicylic acid,
      ofloxacin and L-lactic acid significantly inhibited the uptake of moxifloxacin.
      Furthermore, moxifloxacin uptake was significantly reduced in the presence of
      metabolic and MCT inhibitors. Overall, this study demonstrated an interaction of
      moxifloxacin with Na+ and H+-coupled transporter, most likely MCT1. CONCLUSIONS:
      Apart from the lipophilicity, we anticipate that lowest vitreal half-life of
      intravitreal moxifloxacin compared with other fluoroquinolones may be due to its
      interaction with MCT. This information might be crucial in clinical settings and
      can be further explored to improve vitreous half-life and therapeutic efficacy of
      moxifloxacin.

PMID- 24102497
TI  - Inequalities of dental prosthesis use under universal healthcare insurance.
AB  - BACKGROUND: Social inequalities in oral health exist in various countries. In
      Japan, a country with universal healthcare insurance policy, people can receive
      medical and dental care and pay only 10-30% of the total cost of treatment.
      Additionally, very poor Japanese can receive care without any charge, by the
      benefit of public assistance. These policies are considered to affect oral health
      inequalities. OBJECTIVES: This study examined the association between using a
      dental prosthesis and household income among older Japanese people. METHODS: Self
      administered questionnaires were mailed to subjects as part of the Japan
      Gerontological Evaluation Study (JAGES) project in 2010. Of the 8576 people aged
      65 years or more living in Iwanuma, Japan, 5058 responded. We used 4001
      respondents with no missing values. We stratified into two groups by having 20
      teeth or not. Then, cross-tabulation, univariate logistic regression, and
      multivariate logistic regression were conducted for these two groups. The
      covariates are sex, age, education, and size of household. RESULTS: Of the all
      respondents included in the analyses, poorer respondents tended to have lower
      proportions with 20 or more teeth, and 54.6% respondents used dental prostheses.
      In the respondents with 19 or fewer teeth, higher-income group tended to show
      significantly higher dental prosthesis use. But the poorest income group showed
      high prevalence of dental prosthesis use as same as highest income group.
      Multiple logistic regression among respondents with 19 or fewer teeth showed that
      after adjustment for sex, age, education, and size of household, compared with
      the respondents with annual incomes of US$ <5000, those with incomes of US$5000
      9999 and US$10 000-14 999 had significantly lower odds ratios for using a dental
      prosthesis (OR = 0.48 [95% CI = 0.28-0.83], 0.56 [95% CI = 0.33-0.95],
      respectively). The other respondents did not show significant differences.
      CONCLUSIONS: Although universal healthcare insurance covered dental prostheses, a
      social gradient in dental prosthesis use was still observed. Low-income
      respondents tended to not use dental prosthesis, but the poorest respondents
      showed dental prosthesis utilization as high as the highest income group.

PMID- 24102498
TI  - Different recommendations for empiric first-choice antibiotic treatment of
      uncomplicated urinary tract infections in Europe.
AB  - OBJECTIVE: Uncomplicated urinary tract infection (uUTI) is a common reason for
      antibiotic treatment in primary health care. Due to the increasing prevalence of
      antibiotic-resistant uropathogens it is crucial to use the most appropriate
      antibiotics for first-choice empiric treatment of uUTI. Particularly, it is
      important to avoid antibiotics associated with a high rate of antimicrobial
      resistance. This study compares national recommendations from six European
      countries, investigating recommendations for first-choice antibiotic therapy of
      uUTI. SETTING: General practice in six European countries. METHOD: Searches were
      undertaken on PubMed, the Cochrane Library databases, Google, and Google Scholar.
      Recommendations from different geographical regions in Europe were investigated:
      Northern Europe (Denmark, Sweden), Western Europe (Scotland), Central Europe
      (Germany), Southern Europe (Spain), and Eastern Europe (Croatia). RESULTS: The
      six countries recommended seven different antibiotics. Five countries recommended
      more than one antibiotic as first-choice treatment. Half of the countries
      recommended antibiotics associated with a high rate (> 10-20%) of resistant E.
      coli. All countries recommended at least one antibiotic associated with a low (<
      5%) resistance rate. DISCUSSION: The differences in first-choice treatment of
      uUTI could not be explained by differences in local bacterial aetiology or by
      different patterns of antimicrobial resistance. Despite resistance rates
      exceeding 10-20%, sulphamethizole, trimethoprim. or fluoroquinolones were
      recommended in half of the countries. CONCLUSION: Within the European countries
      there are considerable differences in recommendations for empiric first-choice
      antibiotic treatment of uUTI. In order to reduce the increasing antimicrobial
      resistance in Europe, it is important to agree on the most appropriate
      antibiotics for empiric treatment of uUTI.

PMID- 24102499
TI  - Stability of self-ordered thiol-coated silver nanoparticles: oxidative
      environment effects.
AB  - Here, we study the stability of the 2D organization of thiol-coated silver
      nanoparticles (NPs) by transmission electron microscopy. Whatever the alkyl chain
      length and the nature of the silver precursor, we show the rapid corrosion (over
      a few days) of the NPs by O2 from laboratory air whereas they remain stable for
      several weeks under a nitrogen atmosphere. We show that this phenomenon is
      amplified by the humidity in the air and by thiols trapped in the NP monolayers.
      We obtain evidence of these thiols in excess by infrared and energy-dispersive
      spectroscopies. This study of stability has been extended to gold nanoparticles
      (AuNPs) coated with dodecanethiols. The AuNPs remain stable under laboratory air
      because of the higher redox potential of Au compared to that of Ag and O2. 

PMID- 24102500
TI  - Thermochemistry and kinetics for 2-butanone-1-yl radical (CH2.C(?O)CH2CH3)
      reactions with O2.
AB  - Thermochemistry of reactants, intermediates, transition state structures, and
      products along with kinetics on the association of CH2.C(?O)CH2CH3 (2-butanone-1
      yl) with O2 and dissociation of the peroxy adduct isomers are studied.
      Thermochemical properties are determined using ab initio (G3MP2B3 and G3)
      composite methods along with density functional theory (B3LYP/6-311g(d,p)).
      Entropy and heat capacity contributions versus temperature are determined from
      structures, vibration frequencies, and internal rotor potentials. The
      CH2.C(?O)CH2CH3 radical + O2 association results in a chemically activated peroxy
      radical with 27 kcal mol(-1) excess of energy. The chemically activated adduct
      can react to stabilized peroxy or hydroperoxide alkyl radical adducts, further
      react to lactones plus hydroxyl radical, or form olefinic ketones and a
      hydroperoxy radical. Kinetic parameters are determined from the G3 composite
      methods derived thermochemical parameters, and quantum Rice-Ramsperger-Kassel
      (QRRK) analysis to calculate k(E) with master equation analysis to evaluate
      falloff in the chemically activated and dissociation reactions. One new, not
      previously reported, peroxy chemistry reaction is presented. It has a low barrier
      path and involves a concerted reaction resulting in olefin formation, H2O
      elimination, and an alkoxy radical. 

PMID- 24102501
TI  - Differentiated patterns of cognitive impairment 12 months after severe and
      moderate traumatic brain injury.
AB  - OBJECTIVE: To assess cognitive function at 12 months after moderate and severe
      traumatic brain injury (TBI) separately, as well as improvement from 3 to 12
      months and relationship to global outcome. METHODS: Cognitive function among
      patients with moderate (n = 30, Glasgow Coma Scale score (GCS) 9-3) and severe
      traumatic brain injury (n = 20, GCS score <= 8), recruited from an unselected
      neurosurgical cohort, all with MRI performed in the early phase were assessed
      with a neuropsychological test battery and Glasgow Outcome Scale Extended.
      Healthy volunteers (n = 47) matched for age, gender and years of education served
      as controls. RESULTS: Executive function was reduced at 12-months post-injury in
      patients with both moderate and severe TBI. However, motor function, processing
      speed and memory were reduced only among patients with severe TBI. Both patients
      with moderate and severe TBI improved their processing speed and visual memory.
      Patients with moderate TBI also improved motor function, while patients with
      severe TBI also improved executive function. CONCLUSION: Differentiating between
      patients with moderate and severe TBI yields a more accurate description of
      cognitive deficits and their improvement over time. Further, executive
      dysfunction and attention problems affected the ability to resume independent
      living and employment regardless of injury severity and age.

PMID- 24102502
TI  - Modulating "jousting" C-F---H-C interactions with a bit of hydrogen bonding.
AB  - We have synthesized a series of molecules wherein very close C-F---H-C sigma-bond
      interactions, which we have termed "jousting", can be perturbed through both red-
      and blue-shifted hydrogen bonding effects. These interactions were induced by the
      placement of various functional groups geminal to the H-C bond. "Jousting"
      interactions appear to be an admixture of F---H hydrogen bonding and C-H bond
      compression. The associated electronic effects from changes in the functional
      group at the X-position were also studied. 

PMID- 24102503
TI  - Functional genomics of adaptation to hypoxic cold-stress in high-altitude deer
      mice: transcriptomic plasticity and thermogenic performance.
AB  - In species that are distributed across steep environmental gradients, adaptive
      variation in physiological performance may be attributable to transcriptional
      plasticity in underlying regulatory networks. Here we report the results of
      common-garden experiments that were designed to elucidate the role of regulatory
      plasticity in evolutionary adaptation to hypoxic cold-stress in deer mice
      (Peromyscus maniculatus). We integrated genomic transcriptional profiles with
      measures of metabolic enzyme activities and whole-animal thermogenic performance
      under hypoxia in highland (4350 m) and lowland (430 m) mice from three
      experimental groups: (1) wild-caught mice that were sampled at their native
      elevations; (2) wild-caught/lab-reared mice that were deacclimated to low
      elevation conditions in a common-garden lab environment; and (3) the F(1) progeny
      of deacclimated mice that were maintained under the same low-elevation common
      garden conditions. In each experimental group, highland mice exhibited greater
      thermogenic capacities than lowland mice, and this enhanced performance was
      associated with upregulation of transcriptional modules that influence several
      hierarchical steps in the O(2) cascade, including tissue O(2) diffusion
      (angiogenesis) and tissue O(2) utilization (metabolic fuel use and cellular
      oxidative capacity). Most of these performance-related transcriptomic changes
      occurred over physiological and developmental timescales, suggesting that
      regulatory plasticity makes important contributions to fitness-related
      physiological performance in highland deer mice.

PMID- 24102504
TI  - Sunflower (Helianthus annuus) long-chain acyl-coenzyme A synthetases expressed at
      high levels in developing seeds.
AB  - Long chain fatty acid synthetases (LACSs) activate the fatty acid chains produced
      by plastidial de novo biosynthesis to generate acyl-CoA derivatives, important
      intermediates in lipid metabolism. Oilseeds, like sunflower, accumulate high
      levels of triacylglycerols (TAGs) in their seeds to nourish the embryo during
      germination. This requires that sunflower seed endosperm supports very active
      glycerolipid synthesis during development. Sunflower seed plastids produce large
      amounts of fatty acids, which must be activated through the action of LACSs, in
      order to be incorporated into TAGs. We cloned two different LACS genes from
      developing sunflower endosperm, HaLACS1 and HaLACS2, which displayed sequence
      homology with Arabidopsis LACS9 and LACS8 genes, respectively. These genes were
      expressed at high levels in developing seeds and exhibited distinct subcellular
      distributions. We generated constructs in which these proteins were fused to
      green fluorescent protein and performed transient expression experiments in
      tobacco cells. The HaLACS1 protein associated with the external envelope of
      tobacco chloroplasts, whereas HaLACS2 was strongly bound to the endoplasmic
      reticulum. Finally, both proteins were overexpressed in Escherichia coli and
      recovered as active enzymes in the bacterial membranes. Both enzymes displayed
      similar substrate specificities, with a very high preference for oleic acid and
      weaker activity toward stearic acid. On the basis of our findings, we discuss the
      role of these enzymes in sunflower oil synthesis. 

PMID- 24102505
TI  - The fibrous tapetum of the horse eye.
AB  - The tapetum lucidum is a light-reflective tissue in the eyes of many animals.
      Many ungulates have a fibrous tapetum. The horse has one of the largest eyes of
      any living animal and also has excellent vision in low-light environments. This
      study aimed to clarify the macroscopic tapetal shape, relationship between the
      tapetal thickness and the degree of pigmentation of the retinal pigment
      epithelium (RPE), spatial relationship between the visual streak and the tapetum,
      and wavelength of the light reflected from the tapetum in the horse.
      Macroscopically, weak light revealed the tapetum as a horizontal band located
      dorsal to and away from the optic disc. The tapetum expanded dorsally as the
      illumination increased. The tapetal tissue consisted of lamellae of collagen
      fibrils running parallel to the retinal surface; these spread over almost the
      entire ocular fundus and were thicker in the horizontal band dorsal to the disc.
      Only the horizontal band of the tapetum was covered by unpigmented RPE,
      suggesting that this band reflects light and is responsible for mesopic and
      scotopic vision. The visual streak was located in the ventral part of the
      horizontal band, ventral to the thickest part of the tapetum. The wavelength of
      the light reflected from the horizontal band of the tapetum was estimated from
      the diameter and interfibrous distance of the collagen fibrils to be
      approximately 468 nm. Therefore, the light reflected from the tapetum should be
      more effectively absorbed by rods than by cones, and should not interfere with
      photopic vision. 

PMID- 24102506
TI  - The mouse model of Chlamydia genital tract infection: a review of infection,
      disease, immunity and vaccine development.
AB  - Chlamydia trachomatis is the most common sexually transmitted bacterial infection
      worldwide. The impact of this pathogen on human reproduction has intensified
      research efforts to better understand chlamydial infection and pathogenesis.
      Whilst there are animal models available that mimic many aspects of human
      chlamydial infection, the mouse is regarded as the most practical and widely used
      of the models. Studies in mice have greatly contributed to our understanding of
      the host-pathogen interaction and provided an excellent medium for evaluating
      vaccines. Here we explore the advantages and disadvantages of all animal models
      of chlamydial genital tract infection, with a focus on the murine model and what
      we have learnt from it so far. 

PMID- 24102507
TI  - Automatic feedback to promote safe walking and speech loudness control in persons
      with multiple disabilities: two single-case studies.
AB  - OBJECTIVE: Assessing automatic feedback technologies to promote safe travel and
      speech loudness control in two men with multiple disabilities, respectively.
      METHOD: The men were involved in two single-case studies. In Study I, the
      technology involved a microprocessor, two photocells, and a verbal feedback
      device. The man received verbal alerting/feedback when the photocells spotted an
      obstacle in front of him. In Study II, the technology involved a sound-detecting
      unit connected to a throat and an airborne microphone, and to a vibration device.
      Vibration occurred when the man's speech loudness exceeded a preset level.
      RESULTS: The man included in Study I succeeded in using the automatic feedback in
      substitution of caregivers' alerting/feedback for safe travel. The man of Study
      II used the automatic feedback to successfully reduce his speech loudness.
      CONCLUSION: Automatic feedback can be highly effective in helping persons with
      multiple disabilities improve their travel and speech performance.

PMID- 24102510
TI  - N-acyl-homoserine lactone uptake and systemic transport in barley rest upon
      active parts of the plant.
AB  - Bacteria communicate with each other in a population density-dependent process
      known as quorum sensing. N-acyl-homoserine lactones (HSLs) are the autoinducers
      of Gram-negative bacteria and the best-studied quorum sensing signals so far.
      HSLs induce various responses in plants, including systemic resistance and root
      development. Here, we used different methods, including tritium labelling, sensor
      strain assays and monoclonal antibodies (mAbs), to analyse the uptake and
      translocation of C8- and C10- homoserine lactones into barley (Hordeum vulgare cv
      Barke). Both HSLs were already systemically transported into the shoot at 2 h
      after application. HSL uptake could be inhibited by orthovanadate, demonstrating
      that ABC transporters are involved in the uptake. Root transport occurs
      predominantly via the central cylinder, which was shown by transport inhibition
      via KCl application and autoradiography of root cross-sections. Furthermore, a
      newly established detection method with mAbs allowed the first detection of a
      systemic transport of long-chain HSLs in plants. The coupled use of different HSL
      detection methods demonstrated that the uptake and transport of HSLs into barley
      does not occur passively, but relies, at least partially, on active processes in
      the plant.

PMID- 24102511
TI  - Global variation in cleft palate repairs: an analysis of 352,191 primary cleft
      repairs in low- to higher-middle-income countries.
AB  - Objectives : Resources for repair of cleft lip and palate may be lacking in low-
      and middle-income countries. The Smile Train is a registered charity that
      supports cleft repair in resource-poor settings. In the global health care
      challenge, it has been suggested that many babies born with cleft palates are not
      repaired. This study aims to determine whether any variation exists in the
      proportion of cleft lip and cleft palate repairs undertaken in low- and middle
      income countries. Methods : Data were obtained from the Smile Train database of
      352,191 consecutive cleft operations performed between 2008 and 2011 in low- to
      higher-middle-income countries. The ratio of cleft lip to palate repair was
      analyzed as a function of geographic region and by country income (gross national
      income). Results : A significant correlation exists between both the income of a
      country and its geographical region to the ratio of lip and palate repair
      procedures undertaken. Higher-income countries had a higher ratio of cleft palate
      repairs. Countries in sub-Saharan Africa have the lowest proportion of cleft
      palate repairs. Conclusion : This study emphasizes that many babies born with
      cleft palates in resource-poor regions do not have their palates repaired. This
      finding may be explained by an increased neonatal mortality in cleft palate
      babies. Furthermore, fewer isolated palatal clefts may present to an appropriate
      health care facility or there may be a reluctance to treat cleft palate due to
      concerns regarding higher perioperative risks or the lack of available surgical
      and anesthetic expertise. 

PMID- 24102512
TI  - Association of NFE2L2 and KEAP1 haplotypes with amyotrophic lateral sclerosis.
AB  - Amyotrophic lateral sclerosis (ALS) is a degenerative motor neuron syndrome
      influenced by oxidative stress. The transcription factor Nrf2 and its repressor
      Keap1 constitute an important defence system in cellular protection against
      oxidative stress. Here we hypothesize that common genetic variations in the genes
      NFE2L2 and KEAP1, encoding Nrf2 and Keap1, may influence the risk and phenotype
      of ALS. Five hundred and twenty-two Swedish patients with sporadic ALS (SALS) and
      564 Swedish control subjects were studied. Eight tag SNPs in NFE2L2 and three tag
      SNPs in KEAP1 were genotyped by allelic discrimination and three functional
      NFE2L2 promoter SNPs were genotyped by sequencing. One NFE2L2 haplotype (GGGAC)
      was associated with decreased risk of SALS (OR = 0.62 per allele, p = 0.003) and
      one haplotype in KEAP1 (CGG) was associated with later SALS onset (+3.4 years per
      allele, p = 0.015). When stratified by subgroup, one haplotype in NFE2L2, GAGCAGA
      including three functional promoter SNPs associated with high Nrf2 protein
      expression, was associated with 4.0 years later disease onset per allele in
      subgroup ALS (p = 0.008). In conclusion, these results suggest that variations in
      NFE2L2 and KEAP1, encoding two central proteins in cellular oxidative stress
      defence, may influence SALS pathogenesis.

PMID- 24102513
TI  - Variations of pupil centration and their effects on video eye tracking.
AB  - PURPOSE: To evaluate measurement errors that are introduced in video eye tracking
      when pupil centration changes with pupil size. METHODS: Software was developed
      under Visual C++ to track both pupil centre and corneal centre at 87 Hz sampling
      rate at baseline pupil sizes of 4.75 mm (800 lux room illuminance) and while
      pupil constrictions were elicited by a flashlight. Corneal centres were
      determined by a circle fit through the pixels detected at the corneal margin by
      an edge detection algorithm. Standard deviations for repeated measurements were
      +/- 0.04 mm for horizontal pupil centre position and +/- 0.04 mm for horizontal
      corneal centre positions and +/-0.03 mm for vertical pupil centre position and +/
      0.05 mm for vertical corneal centre position. Ten subjects were tested (five
      female, five male, age 25-58 years). RESULTS: At 4 mm pupil sizes, the pupils
      were nasally decentred relative to the corneal centre by 0.18 +/- 0.19 mm in the
      right eyes and -0.14 +/- 0.22 mm in the left eyes. Vertical decentrations were
      0.30 +/- 0.30 mm and 0.27 +/- 0.29 mm, respectively, always in a superior
      direction. At baseline pupil sizes (the natural pupil sizes at 800 lux) of 4.75
      +/- 0.52 mm, the decentrations became less (right and left eyes: horizontal 0.17
      +/- 0.20 mm and -0.12 +/- 0.22 mm, and vertical 0.26 +/- 0.28 mm and 0.20 +/-
      0.25 mm). While pupil decentration changed minimally in eight of the subjects, it
      shifted considerably in two others. Averaged over all subjects, the shift of the
      pupil centre position per millimetre pupil constriction was not significant
      (right and left eyes: -0.03 +/- 0.07 mm and 0.03 +/- 0.04 mm nasally per mm pupil
      size change, respectively, and -0.04 +/- 0.06 mm and -0.05 +/- 0.12 mm
      superiorly). Direction and magnitude of the changes in pupil centration could not
      be predicted from the initial decentration at baseline pupil sizes. CONCLUSIONS:
      In line with data in the literature, the pupil centre was significantly decentred
      relative to the corneal centre in the nasal and superior direction. Pupil
      decentration changed significantly with pupil size by 0.05 mm on average for 1 mm
      of constriction. Assuming a Hirschberg ratio of 12 degrees  mm(-1) , a shift of
      0.05 mm is equivalent to a measurement error in a Purkinje image-based eye
      tracker of 0.6 degrees . However, the induced measurement error could also exceed
      1.5 degrees  in some subjects for only a 1 mm change in pupil size.

PMID- 24102514
TI  - BCSH/BSBMT guideline: diagnosis and management of veno-occlusive disease
      (sinusoidal obstruction syndrome) following haematopoietic stem cell
      transplantation.
AB  - DIAGNOSIS: It is recommended that the diagnosis of veno-occlusive disease
      (sinusoidal obstruction syndrome) [VOD (SOS)] be based primarily on established
      clinical criteria (modified Seattle or Baltimore criteria) (1A). Ultrasound
      imaging may be helpful in the exclusion of other disorders in patients with
      suspected VOD (SOS) (1C). It is recommended that liver biopsy be reserved for
      patients in whom the diagnosis of VOD (SOS) is unclear and there is a need to
      exclude other diagnoses (1C). It is recommended that liver biopsies are
      undertaken using the transjugular approach in order to reduce the risks
      associated with the procedure (1C). It is suggested that the role of plasminogen
      activator inhibitor 1 levels remains an area for further research but that these
      levels should not form part of the routine diagnostic work-up for VOD (SOS) at
      present (2C). RISK FACTORS: It is recommended that patients are assessed for risk
      factors for VOD (SOS) and that these risk factors are addressed prior to
      haematopoietic stem cell transplantation (1A). PROPHYLAXIS: Defibrotide is
      recommended at a dose of 6.25 mg/kg intravenously four times daily for the
      prevention of VOD (SOS) in children undergoing allogeneic stem cell
      transplantation with the following risk factors: pre-existing hepatic disease,
      second myeloablative transplant, allogeneic transplant for leukaemia beyond
      second relapse, conditioning with busulfan-containing regimens, prior treatment
      with gemtuzumab ozogamicin, diagnosis of primary haemophagocytic
      lymphohistiocytosis, adrenoleucodystrophy or osteopetrosis (1A). Defibrotide is
      suggested at a dose of 6.25 mg/kg intravenously four times daily for the
      prevention of VOD (SOS) in adults undergoing allogeneic stem cell transplantation
      with the following risk factors: pre-existing hepatic disease, second
      myeloablative transplant, allogeneic transplant for leukaemia beyond second
      relapse, conditioning with busulfan-containing regimens, prior treatment with
      gemtuzumab ozogamicin, diagnosis of primary haemophagocytic lymphohistiocytosis,
      adrenoleucodystrophy or osteopetrosis (2B). Prostaglandin E1 is not recommended
      in the prophylaxis of VOD (SOS) due to lack of efficacy and toxicity (1B).
      Pentoxifylline is not recommended in the prophylaxis of VOD (SOS) due to lack of
      efficacy (1A). Ursodeoxycholic acid is suggested for use in the prophylaxis of
      VOD (SOS) (2C). Heparin (unfractionated and low molecular weight) is not
      suggested for use in the prophylaxis of VOD (SOS) due to the risk of increased
      toxicity (2B). Antithrombin is not suggested for the prophylaxis of VOD (SOS) due
      to lack of efficacy (2B). TREATMENT: Defibrotide is recommended in the treatment
      of VOD (SOS) in adults and children (1B). Tissue plasminogen activator is not
      recommended for use in the treatment of VOD (SOS) due to the associated risk of
      haemorrhage (1B). N-acetylcysteine is not routinely recommended for use in the
      treatment of veno-occlusive disease due to lack of efficacy (1A).
      Methylprednisolone may be considered for use in the treatment of veno-occlusive
      disease with the appropriate caveats of caution regarding infection (2C).
      Judicious clinical care, particularly in the management of fluid balance, is
      recommended in the management of VOD (SOS) (1C). Early discussion with critical
      care specialists and a specialist hepatology unit is recommended in the
      management of VOD (SOS) and other treatment options including transjugular
      intrahepatic portosystemic shunt or hepatic transplantation may be considered
      (1C). SUMMARY: A joint working group established by the Haemato-oncology subgroup
      of the British Committee for Standards in Haematology (BCSH) and the British
      Society for Blood and Marrow Transplantation (BSBMT) has reviewed the available
      literature and made recommendations for the diagnosis and management of veno
      occlusive disease of the liver following haematopoietic stem cell transplantation
      (HSCT). This guideline includes recommendations for both prophylaxis and
      treatment of the condition and includes recommendations for children and adults
      undergoing HSCT.

PMID- 24102515
TI  - Changes in aspects of cognitive functioning in young patients with schizophrenia
      during group psychodynamic psychotherapy: a preliminary study.
AB  - BACKGROUND: The "Sveti Ivan" psychiatric hospital in Zagreb, Croatia, offers an
      outpatient Early Intervention Program for psychotic patients. This program
      consists of psycho-educational workshops and group psychodynamic psychotherapy.
      Two important objectives of the program are improving and maintaining adequate
      cognitive functioning. AIMS: The current study examined changes in aspects of
      cognitive functioning in young patients with schizophrenia after 18 months and
      after 3 years of psychodynamic group psychotherapy. METHODS: The study included
      28 patients who attended the Early Intervention Program for young patients with
      psychotic disorders; 10 patients had completed only the psycho-educational part
      of the program (comparative group), and 18 patients continued with group
      psychodynamic psychotherapy (experimental group). All patients completed the
      Revised Beta Examination. RESULTS: We observed a trend in the experimental group
      to achieve higher scores than the comparative group. The results for both groups
      tended to increase with time, and this increase was greater in the experimental
      group. CONCLUSIONS: While acknowledging the limitations of this preliminary
      study, we conclude that participating in psychodynamic group psychotherapy is
      related to increases in the cognitive functioning of patients with schizophrenia,
      and our results provide a sound basis for future research.

PMID- 24102517
TI  - Inter-bacterial correlations in subgingival biofilms: a large-scale survey.
AB  - AIM: Although the complexity of the oral ecology and the ecological differences
      between health and disease are well accepted, a clear view on the dynamics in
      relation to disease is lacking. In this study, the prevalence and abundance of 20
      key oral bacteria was assessed in health and disease and more importantly a
      closer look was given to the inter-bacterial relationships. MATERIALS AND
      METHODS: A blinded microbiological database was analysed in this cross-sectional,
      retrospective study. The database was constructed based on microbiological
      analyses of samples from 6308 patients, with gradations of periodontitis (healthy
      to periodontitis). Data concerning the abundance of 20 oral bacteria and probing
      pocket depth were provided. RESULTS: Porphyromonas gingivalis, Tannerella
      forsythia, Treponema denticola, Eubacterium nodatum, Porphyromonas micra and
      Porphyromonas intermedia showed a clear increase in abundance and prevalence with
      increasing pocket depth. Correlation matrices illustrated that almost all
      microorganisms were in one way correlated to other species and most of these
      correlations were significant. Several beneficial bacteria showed strong
      correlations with other beneficial bacteria. CONCLUSION: Knowledge on bacterial
      correlations can pave the way for new treatment options focusing on restoring the
      shifted balance.

PMID- 24102516
TI  - Synthesis and chemical and biological comparison of nitroxyl- and nitric oxide
      releasing diazeniumdiolate-based aspirin derivatives.
AB  - Structural modifications of nonsteroidal anti-inflammatory drugs (NSAIDs) have
      successfully reduced the side effect of gastrointestinal ulceration without
      affecting anti-inflammatory activity, but they may increase the risk of
      myocardial infarction with chronic use. The fact that nitroxyl (HNO) reduces
      platelet aggregation, preconditions against myocardial infarction, and enhances
      contractility led us to synthesize a diazeniumdiolate-based HNO-releasing aspirin
      and to compare it to an NO-releasing analogue. Here, the decomposition mechanisms
      are described for these compounds. In addition to protection against stomach
      ulceration, these prodrugs exhibited significantly enhanced cytotoxcity compared
      to either aspirin or the parent diazeniumdiolate toward nonsmall cell lung
      carcinoma cells (A549), but they were not appreciably toxic toward endothelial
      cells (HUVECs). The HNO-NSAID prodrug inhibited cylcooxgenase-2 and
      glyceraldehyde 3-phosphate dehydrogenase activity and triggered significant
      sarcomere shortening on murine ventricular myocytes compared to control.
      Together, these anti-inflammatory, antineoplasic, and contractile properties
      suggest the potential of HNO-NSAIDs in the treatment of inflammation, cancer, or
      heart failure. 

PMID- 24102520
TI  - Self-assembly of gold nanoparticles on gallium droplets: controlling charge
      transport through microscopic devices.
AB  - We describe the spontaneous assembly of ligand-stabilized gold nanoparticles on
      the surfaces of gallium droplets in suspension. By subsequent deposition of these
      coated droplets onto substrates with patterned electrodes, we form devices that
      have controlled architecture on the nanometer scale, which allows control of
      electron transport. In particular, we show that microscopic droplets can be
      brought into contact with one another with a monolayer of nanoparticles between
      them, resulting in a junction where electron transport is limited by the Coulomb
      blockade effect. We characterize the gallium surfaces by optical and electron
      microscopy and measurement of the interfacial tension. We measure the current
      voltage characteristics of devices consisting of one or more Ga droplets and
      nanoparticle layers in series. The results agree well with the conventional
      theory of the Coulomb blockade and show how this approach could be used to form
      hierarchically structured electronic devices. 

PMID- 24102519
TI  - Laboratory testing for and diagnosis of nutritional deficiencies in pregnancy
      before and after bariatric surgery.
AB  - OBJECTIVE: Bariatric surgery can reduce the risk of obesity-related complications
      of pregnancy, but may cause essential nutrient deficiencies. To assess adherence
      to laboratory testing guidelines, we examined frequency of testing for and
      diagnosis of deficiency during preconception and pregnancy using claims data in
      women with a delivery and bariatric surgery. METHODS: Retrospective analysis of
      claims from seven Blue Cross/Blue Shield plans between 2002 and 2008. We included
      women with a delivery and bariatric surgery within the study period. We used
      common procedural terminology (CPT) and ICD-9 codes to define laboratory testing
      and deficiencies for iron, folate, vitamin B12, vitamin D, and thiamine. Using
      Student's t-test and chi-square testing, we compared frequency of laboratory
      tests and diagnoses during 12 months preconception and 280 days of pregnancy
      between women with pregnancy before versus after surgery. We used multivariate
      logistic regression to evaluate for predictors of laboratory testing. RESULTS: We
      identified 456 women with pregnancy after bariatric surgery and 338 before
      surgery. The frequency of testing for any deficiency was low (9%-51%), but higher
      in those with pregnancy after surgery (p<0.003). The most common deficiency was
      vitamin B12 (12%-13%) with pregnancy after surgery (p<0.006). Anemia and number
      of health provider visits were independent predictors of laboratory testing.
      CONCLUSION: Women with pregnancy after bariatric surgery were tested for and
      diagnosed with micronutrient deficiencies more frequently than those with
      pregnancy before surgery. However, most laboratory testing occurred in less than
      half the women and was triggered by anemia. Increased testing may help identify
      nutrient deficiencies and prevent consequences for maternal and child health.

PMID- 24102521
TI  - Whole exome sequencing unravels disease-causing genes in consanguineous families
      in Qatar.
AB  - Whole exome sequencing (WES) has greatly facilitated the identification of causal
      mutations for diverse human genetic disorders. We applied WES as a molecular
      diagnostic tool to identify disease-causing genes in consanguineous families in
      Qatar. Seventeen consanguineous families with diverse disorders were recruited.
      Initial mutation screening of known genes related to the clinical diagnoses did
      not reveal the causative mutations. Using WES approach, we identified the
      definitive disease-causing mutations in four families: (i) a novel nonsense
      homozygous (c.1034C>G) in PHKG2 causing glycogen storage disease type 9C (GSD9C)
      in a male with initial diagnosis of GSD3; (ii) a novel homozygous 1-bp deletion
      (c.915del) in NSUN2 in a male proband with Noonan-like syndrome; (iii) a
      homozygous SNV (c.1598C>G) in exon 11 of IDUA causing Hurler syndrome in a female
      proband with unknown clinical diagnosis; (iv) a de novo known splicing mutation
      (c.1645+1G>A) in PHEX in a female proband with initial diagnosis of autosomal
      recessive hypophosphatemic rickets. Applying WES as a diagnostic tool led to the
      unambiguous identification of disease-causing mutations in phenotypically complex
      disorders or correction of the initial clinical diagnosis in ~25% of our cases.

PMID- 24102522
TI  - Inhibition of c-Met promoted apoptosis, autophagy and loss of the mitochondrial
      transmembrane potential in oridonin-induced A549 lung cancer cells.
AB  - OBJECTIVE: Herein, inhibition of hepatocyte growth factor receptor, c-Met,
      significantly increased cytochrome c release and Bax/Bcl-2 ratio, indicating that
      c-Met played an anti-apoptotic role. The following experiments are to elucidate
      this anti-apoptotic mechanism, then the effect of c-Met on autophagy has also
      been discussed. METHODS: Investigated was the influence of c-Met on apoptosis,
      autophagy and loss of mitochondrial transmembrane potential (Deltapsim), and the
      relevant proteins were examined. KEY FINDINGS: First, we found that activation of
      extracellular signal-regulated kinase (ERK), p53 was promoted by c-Met
      interference. Subsequent studies indicated that ERK was the upstream effector of
      p53, and this ERK-p53 pathway mediated release of cytochrome c and up-regulation
      of Bax/Bcl-2 ratio. Secondly, the inhibition of c-Met augmented oridonin-induced
      loss of mitochondrial transmembrane potential (Deltapsim), resulting apoptosis.
      Finally, the inhibition of c-Met increased oridonin-induced A549 cell autophagy
      accompanied by Beclin-1 activation and conversion from microtubule-associated
      protein light chain 3 (LC3)-I to LC3-II. Activation of ERK-p53 was also detected
      in autophagy process and could be augmented by inhibition of c-Met. Moreover,
      suppression of autophagy by 3-methyladenine (3-MA) or small interfering RNA
      against Beclin-1 or Atg5 decreased oridonin-induced apoptosis. Inhibition of
      apoptosis by pan-caspase inhibitor (z-VAD-fmk) decreased oridonin-induced
      autophagy as well and Loss of Deltapsim also occurred during autophagic process.
      CONCLUSION: Thus, inhibiting c-Met enhanced oridonin-induced apoptosis, autophagy
      and loss of Deltapsim in A549 cells.

PMID- 24102523
TI  - (S)-1-(Pent-4'-enoyl)-4-(hydroxymethyl)-azetidin-2-one derivatives as inhibitors
      of human fatty acid amide hydrolase (hFAAH): synthesis, biological evaluation and
      molecular modelling.
AB  - A series of lipophilic ester derivatives (2a-g) of (S)-1-(pent-4'-enoyl)-4
      (hydroxymethyl)-azetidin-2-one has been synthesised in three steps from (S)-4
      (benzyloxycarbonyl)-azetidin-2-one and evaluated as novel, reversible, beta
      lactamic inhibitors of endocannabinoid-degrading enzymes (human fatty acid amide
      hydrolase (hFAAH) and monoacylglycerol lipase (hMAGL)). The compounds showed IC50
      values in the micromolar range and selectivity for hFAAH versus hMAGL. The
      unexpected 1000-fold decrease in activity of 2a comparatively to the known
      regioisomeric structure 1a (i.e. lipophilic chains placed on N1 and C3 positions
      of the beta-lactam core) could be explained on the basis of docking studies into
      a revisited model of hFAAH active site, considering one or two water molecules in
      interaction with the catalytic triad.

PMID- 24102524
TI  - Exploring QSARs of the interaction of flavonoids with GABA (A) receptor using
      MLR, ANN and SVM techniques.
AB  - Quantitative Structure-Activity Relationship (QSAR) models for binding affinity
      constants (log Ki) of 78 flavonoid ligands towards the benzodiazepine site of
      GABA (A) receptor complex were calculated using the machine learning methods:
      artificial neural network (ANN) and support vector machine (SVM) techniques. The
      models obtained were compared with those obtained using multiple linear
      regression (MLR) analysis. The descriptor selection and model building were
      performed with 10-fold cross-validation using the training data set. The SVM and
      MLR coefficient of determination values are 0.944 and 0.879, respectively, for
      the training set and are higher than those of ANN models. Though the SVM model
      shows improvement of training set fitting, the ANN model was superior to SVM and
      MLR in predicting the test set. Randomization test is employed to check the
      suitability of the models.

PMID- 24102525
TI  - Inhibition of anthrax lethal factor by curcumin and chemically modified curcumin
      derivatives.
AB  - Curcumin (diferuloylmethane), the active ingredient in the eastern spice turmeric
      (Curcuma longa), has been shown to inhibit the activities of numerous enzymes and
      signaling molecules involved in cancer, bacterial and viral infections and
      inflammatory diseases. We have investigated the inhibitory activities of curcumin
      and chemically modified curcumin (CMC) derivatives toward lethal factor (LF), the
      proteolytic component of anthrax toxin produced by the bacterium Bacillus
      anthracis. Curcumin (Compound 1) appears to inhibit the catalytic activity of LF
      through a mixture of inhibitory mechanisms, without significant compromise to the
      binding of oligopeptide substrates, and one CMC derivative in particular,
      Compound 3 (4-phenylaminocarbonylbis-demethoxycurcumin), is capable of inhibiting
      LF with potency comparable with the parent compound, while also showing improved
      solubility and stability. The quantitative reduction in catalytic activity
      achieved by the different CMC derivatives appears to be a function of the
      proportion of the multiple mechanisms through which they inhibit the enzyme.

PMID- 24102526
TI  - Synthesis and biological evaluation of (E)-1-(substituted)-3-phenylprop-2-en-1
      ones bearing rhodanines as potent anti-microbial agents.
AB  - Herein, we report the design, syntheses and in vitro anti-microbial activity of
      two series of rhodanines with chalcone moiety. Anti-microbial tests showed that
      some of the synthesized compounds exhibited good inhibition (MIC = 1-8 ug/mL)
      against multi-drug-resistant Gram-positive organisms, including methicillin
      resistant and quinolone-resistant Staphylococcus aureus, in which the compound 4g
      was found to be the most potent with minimum inhibitory concentration (MIC) value
      of 1 ug/mL against two methicillin-resistant S. aureus.

PMID- 24102527
TI  - Chemical profiling and in vitro biological effects of Cardiospermum halicacabum
      L. (Sapindaceae) aerial parts and seeds for applications in neurodegenerative
      disorders.
AB  - Cardiospermum halicacabum is widely used in traditional medicine. Previous
      studies have focused on the aerial parts, while the seeds have been poorly
      investigated. This work aimed to analyse the chemical composition of extracts
      from aerial parts and seeds obtained using Naviglio and Soxhlet (PN, PS, and SN,
      SS, respectively), the inhibitory properties against tyrosinase,
      acetylcholinesterase (AChE), and butyrylcholinesterase (BChE) and the antioxidant
      effects. PN total extract showed significant anti-tyrosinase activity (IC50 value
      of 10.8 ug/mL). After partitioning with n-hexane, an HPLC method for analysing
      chemical constituents was established. Apigenin, luteolin, and apigenin-7-O
      glucoside are the predominant constituents. SN n-hexane fraction was the most
      active inhibitor of BChE (IC50 of 57.9 ug/mL). Gas chromatography-mass
      spectrometry analysis revealed fatty acids, including eicosanoic acid, methyl 11
      eicosenoate and oleic acid, as the major constituents. These findings suggest the
      potentiality of both seeds and aerial parts of C. halicacabum in the treatment of
      neurological disorders.

PMID- 24102528
TI  - Experimental and theoretical study of the kinetics and mechanism of the reaction
      of OH radicals with dimethyl ether.
AB  - The reaction of OH with dimethyl ether (CH3OCH3) has been studied from 195 to 850
      K using laser flash photolysis coupled to laser induced fluorescence detection of
      OH radicals. The rate coefficient from this work can be parametrized by the
      modified Arrhenius expression k = (1.23 +/- 0.46) * 10(-12) (T/298)(2.05+/-0.23)
      exp((257 +/- 107)/T) cm(3) molecule(-1) s(-1). Including other recent literature
      data (923-1423 K) gives a modified Arrhenius expression of k1 = (1.54 +/- 0.48) *
      10(-12) (T/298 K)(1.89+/-0.16) exp((184 +/- 112)/T) cm(3) molecule(-1) s(-1) over
      the range 195-1423 K. Various isotopomeric combinations of the reaction have also
      been investigated with deuteration of dimethyl ether leading to a normal isotope
      effect. Deuteration of the hydroxyl group leads to a small inverse isotope
      effect. To gain insight into the reaction mechanisms and to support the
      experimental work, theoretical studies have also been undertaken calculating the
      energies and structures of the transition states and complexes using high level
      ab initio methods. The calculations also identify pre- and post-reaction
      complexes. The calculations show that the pre-reaction complex has a binding
      energy of ~22 kJ mol(-1). Stabilization into the complex could influence the
      kinetics of the reaction, especially at low temperatures (<300 K), but there is
      no direct evidence of this occurring under the experimental conditions of this
      study. The experimental data have been modeled using the recently developed
      MESMER (master equation solver for multi energy well reactions) code; the
      calculated rate coefficients lie within 16% of the experimental values over the
      temperature range 200-1400 K with a model based on a single transition state.
      This model also qualitatively reproduces the observed isotope effects, agreeing
      closely above ~600 K but overestimating them at low temperatures. The low
      temperature differences may derive from an inadequate treatment of tunnelling
      and/or from an enhanced role of an outer transition state leading to the pre
      reaction complex.

PMID- 24102529
TI  - Reprogramming of Vibrio harveyi gene expression during adaptation in cold
      seawater.
AB  - The life and survival of the marine bacterium Vibrio harveyi during its
      adaptation in natural aquatic systems is highly influenced by the availability of
      nutrients and temperature. To learn about adaptation strategies evolved by this
      bacterium to cope with drastic temperature downshifts and nutrients depletion, we
      have studied the phenotypical and gene expression changes occurring in V. harveyi
      during its adaptation to cold seawater. We found that incubation in cold seawater
      up to 12 h did not cause any significant morphological changes in V. harveyi and
      had no effect on the number of viable and culturable cells. Microarray analysis
      revealed that the V. harveyi response to cold seawater leads to up- and
      downregulation of numerous genes controlling the central carbon metabolism,
      nucleotide and amino acid biosynthesis as well as DNA repair. In addition,
      expression of some genes controlling biosynthesis of lipids, molecular transport,
      and energy production was altered to likely affect the composition and properties
      of the V. harveyi cell envelope, thus implying the putative role of this
      compartment in adaptation to stress. Here, we discuss these results with regard
      to the putative adaptive responses likely triggered by V. harveyi to cope with
      environmental challenges in natural aquatic systems.

PMID- 24102530
TI  - Accumulation of anthocyanins in tomato skin extends shelf life.
AB  - Shelf life is one of the most important traits for the tomato (Solanum
      lycopersicum) industry. Two key factors, post-harvest over-ripening and
      susceptibility to post-harvest pathogen infection, determine tomato shelf life.
      Anthocyanins accumulate in the skin of Aft/Aft atv/atv tomatoes, the result of
      introgressing alleles affecting anthocyanin biosynthesis in fruit from two wild
      relatives of tomato, which results in extended fruit shelf life. Compared with
      ordinary, anthocyanin-less tomatoes, the fruits of Aft/Aft atv/atv keep longer
      during storage and are less susceptible to Botrytis cinerea, a major tomato
      pathogen, post-harvest. Using genetically modified tomatoes over-producing
      anthocyanins, we confirmed that skin-specific accumulation of anthocyanins in
      tomato is sufficient to reduce the susceptibility of fruit to Botrytis cinerea.
      Our data indicate that accumulation of anthocyanins in tomato fruit, achieved
      either by traditional breeding or genetic engineering can be an effective way to
      extend tomato shelf life.

PMID- 24102531
TI  - Electronic and ligand properties of annelated normal and abnormal (mesoionic) N
      heterocyclic carbenes: a theoretical study.
AB  - The effect of annelation and carbonylation on the electronic and ligating
      properties of N-heterocyclic carbenes (NHCs) has been studied quantum chemically.
      The thermodynamic and kinetic stability of these NHCs have been assessed on the
      basis of their singlet-triplet and HOMO-LUMO gaps respectively. Both annelation
      and carbonylation have been found to decrease the stability of NHCs. Compared to
      nonannelated carbenes, annelated and carbonylated carbenes are found to be weaker
      sigma donors but better pi acceptors. However, the effect of carbonylation is
      more pronounced than annelation toward increasing the pi acidity of the NHCs. The
      reactivity of these carbenes has been discussed in terms of nucleophilicity and
      electrophilicity indices. The calculated values of the relative redox potential
      and (31)P NMR chemical shifts of corresponding carbene-phosphinidene adducts have
      been found to correlate well with the pi acidity of the NHCs. 

PMID- 24102532
TI  - Delusional jealousy and person directed hostility: 5-year follow-up of a patient
      after anoxic brain injury.
AB  - AIM: This study presents a case report on the emergence of delusional jealousy
      and person-directed hostility in a patient following anoxic brain injury. CASE
      STUDY: The patient did not have a pre-injury history of mental illness, nor a
      family history of a psychotic disorder. This patient was followed-up over a 5
      year period and his history of treatment response, violence risk management and
      successful rehabilitation are presented. This study also highlights issues in
      relation to continuation of treatment with antipsychotic medication, use of
      compulsory admission under the Mental Health Act and principles of risk
      assessment and risk management.

PMID- 24102533
TI  - What is your diagnosis? Fluid surrounding a submandibular mass from a horse.

PMID- 24102534
TI  - Cluster analysis identifies characteristic phenotypes of asthma with accelerated
      lung function decline.
AB  - OBJECTIVE: While the majority of individuals with asthma retain normal lung
      function over time, some exhibit accelerated lung function decline. Preservation
      of lung function is an important aspect of asthma management. Whether the asthma
      guidelines can prevent lung function decline remains controversial. This study
      was performed to determine the distribution of asthmatic subjects with greater
      lung function decline and to identify characteristic clinical features of such
      subjects treated in accordance with clinical guidelines by using hierarchical
      cluster analysis. METHODS: Eighty-six asthmatic subjects without a history of
      smoking were assessed with respect to eight variables selected from clinical
      phenotypes by using step-wise multiple regression analysis. Hierarchical cluster
      analysis using Ward's method generated a dendrogram for estimation of the number
      of clusters within the population and the differences between them. RESULTS:
      Three distinct clusters were identified. Cluster 1 (n = 40) comprised women with
      late-onset asthma. Cluster 2 (n = 17) comprised subjects with early-onset asthma,
      atopy and long disease duration. Cluster 3 (n = 29) predominantly comprised older
      men who had late-onset asthma, a lower prevalence of exacerbation and a lower
      predicted % forced expiratory volume in 1 s (FEV1) at baseline. Subjects in
      cluster 3 showed a mean decline in FEV1 of 69 mL/year, which was the greatest
      lung function decline among the three clusters. CONCLUSION: We identified a
      subgroup of patients with accelerated lung function decline despite appropriate
      asthma treatment based on guidelines constructed by using subjective symptoms.

PMID- 24102535
TI  - A comparison of single particle tracking and temporal image correlation
      spectroscopy for quantitative analysis of endosome motility.
AB  - Single particle tracking (SPT) is becoming a standard method to extract transport
      parameters from time-lapse image sequences of fluorescent vesicles in living
      cells. Another method to obtain these data is temporal image correlation
      spectroscopy (TICS), but this method is less often used for measurement of
      intracellular vesicle transport. Here, we present an extensive comparison of SPT
      and TICS. First we examine the effect of photobleaching, shading and noise on SPT
      and TICS analysis using simulated image sequences. To this end, we developed a
      simple photophysical model, which relates spatially varying illumination
      intensity to the bleaching propensity and fluorescence intensity of the moving
      particles. We found that neither SPT nor TICS are affected by photobleaching per
      se, but the transport parameters obtained by both methods are sensitive to the
      signal-to-noise ratio. In addition, the number of obtained trajectories in SPT is
      affected by noise. Diffusion constants determined by TICS are significantly
      overestimated when large immobile fluorescent structures are present in the image
      sequences, while the opposite is true for SPT. To improve the performance of both
      techniques, we compare three different methods for image denoising. Appropriate
      denoising significantly reduced the effect of noise and of immobile structures on
      both methods. Shape fluctuations of simulated particles had a more pronounced
      effect on TICS than on SPT analysis. In denoised images of fluorescent beads or
      cytosolic vesicles containing fluorescent protein NPC2 in human skin fibroblast
      cells, the transport parameters acquired by SPT and TICS were comparable
      emphasizing the value of both analysis methods. 

PMID- 24102539
TI  - Strong selection genome-wide enhances fitness trade-offs across environments and
      episodes of selection.
AB  - Fitness trade-offs across episodes of selection and environments influence life
      history evolution and adaptive population divergence. Documenting these trade
      offs remains challenging as selection can vary in magnitude and direction through
      time and space. Here, we evaluate fitness trade-offs at the levels of the whole
      organism and the quantitative trait locus (QTL) in a multiyear field study of
      Boechera stricta (Brassicaceae), a genetically tractable mustard native to the
      Rocky Mountains. Reciprocal local adaptation was pronounced for viability, but
      not for reproductive components of fitness. Instead, local genomes had a
      fecundity advantage only in the high latitude garden. By estimating realized
      selection coefficients from individual-level data on viability and reproductive
      success and permuting the data to infer significance, we examined the genetic
      basis of fitness trade-offs. This analytical approach (Conditional Neutrality
      Antagonistic Pleiotropy, CNAP) identified genetic trade-offs at a flowering
      phenology QTL (costs of adaptation) and revealed genetic trade-offs across
      fitness components (costs of reproduction). These patterns would not have emerged
      from traditional ANOVA-based QTL mapping. Our analytical framework can be applied
      to other systems to investigate fitness trade-offs. This task is becoming
      increasingly important as climate change may alter fitness landscapes,
      potentially disrupting fitness trade-offs that took many generations to evolve. 

PMID- 24102541
TI  - Dynamic mean field theory for lattice gas models of fluid mixtures confined in
      mesoporous materials.
AB  - We present the extension of dynamic mean field theory (DMFT) for fluids in porous
      materials (Monson, P. A. J. Chem. Phys. 2008, 128, 084701) to the case of
      mixtures. The theory can be used to describe the relaxation processes in the
      approach to equilibrium or metastable equilibrium states for fluids in pores
      after a change in the bulk pressure or composition. It is especially useful for
      studying systems where there are capillary condensation or evaporation
      transitions. Nucleation processes associated with these transitions are emergent
      features of the theory and can be visualized via the time dependence of the
      density distribution and composition distribution in the system. For mixtures an
      important component of the dynamics is relaxation of the composition distribution
      in the system, especially in the neighborhood of vapor-liquid interfaces. We
      consider two different types of mixtures, modeling hydrocarbon adsorption in
      carbon-like slit pores. We first present results on bulk phase equilibria of the
      mixtures and then the equilibrium (stable/metastable) behavior of these mixtures
      in a finite slit pore and an inkbottle pore. We then use DMFT to describe the
      evolution of the density and composition in the pore in the approach to
      equilibrium after changing the state of the bulk fluid via composition or
      pressure changes. 

PMID- 24102540
TI  - Three-dimensional skeletal kinematics of the shoulder girdle and forelimb in
      walking Alligator.
AB  - Crocodylians occupy a key phylogenetic position for investigations of archosaur
      locomotor evolution. Compared to the well-studied hindlimb, relatively little is
      known about the skeletal movements and mechanics of the forelimb. In this study,
      we employed manual markerless XROMM (X-ray Reconstruction Of Moving Morphology)
      to measure detailed 3-D kinematics of the shoulder girdle and forelimb bones of
      American alligators (Alligator mississippiensis) walking on a treadmill. Digital
      models of the interclavicle, scapulocoracoid, humerus, radius and ulna were
      created using a 3-D laser scanner. Models were articulated and aligned to
      simultaneously recorded frames of fluoroscopic and standard light video to
      reconstruct and measure joint motion. Joint coordinate systems were established
      for the coracosternal, glenohumeral and elbow joints. Our analysis revealed that
      the limb joints only account for about half of fore/aft limb excursion; the
      remaining excursion results from shoulder girdle movements and lateral bending of
      the vertebral column. Considerable motion of each scapulocoracoid relative to the
      vertebral column is consistent with coracosternal mobility. The hemisellar design
      of the glenohumeral joint permits some additional translation, or sliding in the
      fore-aft plane, but this movement does not have much of an effect on the distal
      excursion of the bone. 

PMID- 24102542
TI  - Elimination of the antimicrobial action of the organoarsenical cancer
      therapeutic, 4-(N-(S-glutathionylacetyl)amino) phenylarsonous acid, before
      finished product sterility testing.
AB  - OBJECTIVES: Arsenical compounds have been used therapeutically for over 2000
      years finding particular relevance as antimicrobials. After being replaced by
      more selective and consequently less toxic antibiotics in the last century,
      arsenicals have recently made a resurgence as anticancer drugs (specifically
      arsenic trioxide and its derivatives). Arsenical parenteral formulations require
      post-manufacture sterility testing; however, their intrinsic antimicrobial
      activity must be neutralised before testing to eliminate the possibility of false
      (no-growth) test results. METHODS: A range of thiol-containing compounds was
      screened to establish a suitable deactivation agent for the novel organoarsenical
      compound, 4-(N-(S-glutathionylacetyl)amino) phenylarsonous acid (GSAO).
      Dimercatopropanol (DMP) was found to successful deactivate GSAO and was validated
      according to pharmacopoeial sterility test guidelines (specifically the method
      suitability test/sterility validation test). KEY FINDINGS: DMP is an effective
      way of deactivating GSAO before sterility testing and can be used for
      pharmacopoeial sterility tests. Our results affirm previous research highlighting
      the sensitivity of Staphylococcus aureus to arsenical compounds CONCLUSIONS: A
      method of deactivating the arsenical drug GSAO before the post-manufacture
      sterility test was established and validated. DMP is a commonly used
      chelator/deactivation agent so this work may have implications for other
      inorganic therapeutic agents.

PMID- 24102543
TI  - Commercially available blood storage containers.
AB  - Plastic blood bags improve the safety and effectiveness of blood component
      separation and storage. Progress towards optimal storage systems is driven by
      medical, scientific, business and environmental concerns and is limited by
      available materials, consumer acceptance and manufacturing and regulatory
      concerns. Blood bag manufacturers were invited to submit lists of the bags they
      manufacture. The lists were combined and sorted by planned use. The lists were
      analysed by experts to assess the degree to which the products attend to
      scientific problems. Specific issues addressed included the use of di-ethylhexyl
      phthalate (DEHP) as plasticizer for polyvinyl chloride (PVC) blood bags, the
      size, material and thickness of platelet bags, and the fracture resistance of
      plasma bags. Alternatives to DEHP for red blood cell (RBC) storage exist, but are
      mostly in a developmental stage. Plastic bags (DEHP-free, PVC-free) for platelet
      storage with better gas diffusion capabilities are widely available. Alternatives
      for plasma storage with better fracture resistance at low temperatures exist.
      Most RBC products are stored in DEHP-plasticized PVC as no fully satisfactory
      alternative exists that ensures adequate storage with low haemolysis. A variety
      of alternative platelet storage systems are available, but their significance -
      other than improved oxygen transport - is poorly understood. The necessity to
      remove DEHP from blood bags still needs to be determined. 

PMID- 24102544
TI  - PTEN inactivation by germline/somatic c.950_953delTACT mutation in patients with
      Lhermitte-Duclos disease manifesting progressive phenotypes.
AB  - Lhermitte-Duclos disease (LDD), a neurological manifestation of Cowden syndrome
      (CS), is a rare and benign cerebellar disorder, featured by dysplastic cerebellar
      ganglion cells which replace granular and Purkinje cells. Phosphatase and Tensin
      Homolog (PTEN) is confirmed as the susceptibility gene for CS which represents
      the most complex features and is not easily recognizable. We reported two index
      patients with LDD diagnosed either in an isolated form or coexist with CS. These
      two patients displayed progressive though comparable phenotypes and were found to
      carry an identical PTEN c.950_953delTACT mutation in either germline or somatic
      sources of DNA, respectively. Negative or moderate expression levels of PTEN were
      validated by immunohistochemistry in the corresponding patients' affected
      tissues. This study has revealed a novel pathogenicity locus to LDD/CS as a
      candidate for early molecular diagnosis. In addition, the differential PTEN
      mutation status with corresponding LDD phenotypes suggests a potential
      correlation between germline or somatic mutation and coexisting LDD/CS or
      isolated LDD, respectively. Furthermore, our data could lend some reference to
      the underlying molecular mechanism of LDD pathogenesis in the future. 

PMID- 24102545
TI  - Multilevel analysis of the association between posterior restorations and
      gingival health in young adults: a population-based birth cohort.
AB  - OBJECTIVE: To investigate the association of direct posterior restorations with
      gingival bleeding and dental calculus in young adults from a birth cohort.
      METHODS: A representative sample (n = 720) of 5914 infants born live in Pelotas,
      Brazil, in 1982, were prospectively investigated, and posterior restorations and
      periodontal health outcomes assessed when they were 24 years of age. Tooth-level
      exploratory variables included the presence and number of restoration's surfaces.
      Demographic and socio-economic characteristics, oral health instructions, dental
      floss usage, dental caries presence and smoking were also considered whilst
      gingival bleeding and dental calculus were the outcomes. Multilevel logistic
      regression was carried out. RESULTS: Class I cavities were found in 15.2% (95% CI
      14.5-15.9) of the teeth and class II in 3.6% (3.3-4.0). Percentage of teeth with
      gingival bleeding was 6.1% (5.6-6.6) and that with dental calculus 22% (21.2
      22.8). Even after all the individual variables were controlled for, the presence
      of a class I [OR1.51 (1.14-2.00)] and class II [OR 1.76 (1.04-2.97)] cavities was
      positively associated with gingival bleeding. Class I [OR1.36 (1.13-1.65)] and
      Class II [OR1.80 (1.28-2.53)] cavities were associated with dental calculus also.
      CONCLUSIONS: Posterior restoration and higher number of restored surfaces was
      associated with a higher prevalence of gingival bleeding and dental calculus
      around the restoration.

PMID- 24102547
TI  - Understanding health anxiety following breast cancer diagnosis.
AB  - Health anxiety is a persistent fear of illness or disease that often involves the
      misinterpretation of bodily symptoms as signs of serious illness. Evidence shows
      that health anxiety affects a proportion of women following a diagnosis of breast
      cancer, but there are some limitations to how health anxiety has been measured.
      The objectives of this study were to (1) provide an estimate of clinically
      elevated health anxiety in women after a diagnosis of breast cancer using a
      validated measure appropriate for medical populations and (2) understand patient,
      disease, and anxiety/vulnerability variables that predict health anxiety in this
      group. Canadian women (n = 137) diagnosed with breast cancer within the past five
      years completed an online survey measuring health anxiety, along with patient,
      disease, and anxiety/vulnerability variables. Clinically significant health
      anxiety was reported by 23.4% of the sample. The regression model revealed that
      younger age, more advanced stage of breast cancer, increased cognitive anxiety
      sensitivity, and greater body vigilance were significant unique predictors of
      health anxiety. These findings highlight that a proportion of women report
      substantial health anxiety following breast cancer diagnosis, with a combination
      of patient, disease, and anxiety/vulnerability variables associated with the
      experience. Further research is needed to better understand the impact of health
      anxiety in this population.

PMID- 24102548
TI  - Age-related difference in perceptual responses and interface pressure
      requirements for driver seat design.
AB  - Due to typical physiological changes with age, older individuals are likely to
      have different perceptual responses to and different needs for driver-seat
      interface design. To assess this, a study was conducted in which a total of 22
      younger and older participants completed six short-term driving sessions. Three
      subjective ratings (comfort, discomfort and overall) were obtained, along with 36
      driver-seat interface pressure measures, and were used to assess differences and
      similarities between the two age groups. For both age groups, localised comfort
      ratings were more effective at distinguishing between driver seats and
      workspaces. Older individuals appeared to be less sensitive to discomfort than
      younger individuals. Across age groups, two distinct processes were used in
      determining whole-body comfort and discomfort perceptions based on localised
      comfort/discomfort perceptions. Whole-body discomfort levels were largely
      affected by lower back discomfort in the younger group versus upper back
      discomfort in the older group. Four specific pressure measures at several body
      regions differed between the age groups, suggesting distinct contract pressure
      requirements and loading patterns among these groups.

PMID- 24102549
TI  - An overview of chemical straightening of human hair: technical aspects, potential
      risks to hair fibre and health and legal issues.
AB  - Personal image, as it relates to external beauty, has attracted much attention
      from the cosmetic industry, and capillary aesthetics is a leader in consumption
      in this area. There is a great diversity of products targeting both the treatment
      and beautification of hair. Among them, hair straighteners stand out with a high
      demand by costumers aiming at beauty, social acceptance and ease of daily hair
      maintenance. However, this kind of treatment affects the chemical structure of
      keratin and of the hair fibre, bringing up some safety concerns. Moreover, the
      development of hair is a dynamic and cyclic process, where the duration of growth
      cycles depends not only on where hair grows, but also on issues such as the
      individual's age, dietary habits and hormonal factors. Thus, although hair fibres
      are composed of dead epidermal cells, when they emerge from the scalp, there is a
      huge variation in natural wave and the response to hair cosmetics. Although it is
      possible to give the hair a cosmetically favourable appearance through the use of
      cosmetic products, for good results in any hair treatment, it is essential to
      understand the mechanisms of the process. Important information, such as the
      composition and structure of the hair fibres, and the composition of products and
      techniques available for hair straightening, must be taken into account so that
      the straightening process can be designed appropriately, avoiding undesirable
      side effects for hair fibre and for health. This review aims to address the
      morphology, chemical composition and molecular structure of hair fibres, as well
      as the products and techniques used for chemical hair relaxing, their potential
      risk to hair fibre and to health and the legal aspects of their use. 

PMID- 24102550
TI  - Bone growth, limb proportions and non-specific stress in archaeological
      populations from Croatia.
AB  - BACKGROUND: The effect of environmental factors and, in particular, non-specific
      stress on the growth patterns of limbs and other body dimensions of children from
      past populations is not well understood. AIMS: This study assesses whether growth
      of mediaeval and post-mediaeval children aged between 0-11.5 years from Adriatic
      (coastal) and continental Croatia varies by region and by the prevalence and type
      of non-specific stress. METHODS: Dental ages were estimated using the Moorrees,
      Fanning and Hunt (MFH) scoring method. Growth of long bone diaphyses (femur,
      tibia, humerus, radius and ulna) was assessed by using a composite Z-score
      statistic (CZS). Clavicular length was measured as a proxy for upper trunk width,
      distal metaphyseal width of the femur was measured as a proxy for body mass and
      upper and lower intra-limb indices were calculated. Differences between sub-sets
      sampled by (a) region and (b) active vs healed non-specific stress indicators and
      (c) intra-limb indices were tested by Mann--Whitney U-tests and Analysis of
      Covariance (ANCOVA). RESULTS: Adriatic children attained larger dimensions-per
      age than continental children. Children with healed stress lesions had larger
      dimensions-per-age than those with active lesions. No inter-regional difference
      was found in intra-limb indices. CONCLUSION: These findings highlight the
      complexity of growth patterns in past populations and indicate that variation in
      environmental conditions such as diet and differences in the nature of non
      specific stress lesions both exert a significant effect on long bone growth.

PMID- 24102551
TI  - Caffeine and other methylxanthines as interceptors of food-borne aromatic
      mutagens: inhibition of Trp-P-1 and Trp-P-2 mutagenic activity.
AB  - Caffeine is one of the most important biologically active food components. In
      this article, we demonstrate that caffeine and other methylxanthines
      significantly reduce the mutagenic activity of two food-derived heterocyclic
      aromatic amines, Trp-P-1 and Trp-P-2 in the Salmonella typhimurium TA98 strain.
      Moreover, protection against Trp-P-1-induced mutagenicity was independent of
      liver S9 enzymatic fraction, suggesting that mechanisms other than modulation of
      mutagen bioactivation can contribute to the observed protective effects. UV-vis
      spectroscopy and computational studies revealed that methylxanthines intercept
      Trp-P-1 and Trp-P-2 in noncovalent molecular complexes, with association
      constants (KAC) in the 10(2) M(-1) range. Enthalpy values (DeltaH about -30
      kJ.mol(-1)) of mutagen-methylxanthine heterocomplexation obtained
      microcalorimetrically correspond to stacking (pi-pi) interactions. Finally, we
      demonstrated that the biological activity of Trp-P-1 and Trp-P-2 is strictly
      dependent on the presence of the mutagen in a free (unbound with methylxanthine)
      form, suggesting that mutagen sequestration in stacking heterocomplexes with
      methylxanthines can decrease its bioavailability and diminish its biological
      effects. 

PMID- 24102552
TI  - Overfeeding and genetics affect the composition of intestinal microbiota in Anas
      platyrhynchos (Pekin) and Cairina moschata (Muscovy) ducks.
AB  - To investigate the effect of overfeeding on the ileal and cecal microbiota of two
      genotypes of ducks (Pekin and Muscovy), high-throughput 16S rRNA gene-based
      pyrosequencing was used. The ducks were overfed for 12 days with 58% maize flour
      and 42% maize grain. Samples were collected before the overfeeding period (at 12
      weeks), at 13 weeks, at 14 weeks, and 3 h after feeding. In parallel, ducks fed
      ad libitum were killed at the same ages. Whatever the digestive segment, the
      genotype, and the level of intake, Firmicutes and Bacteroidetes are the dominant
      phyla in the bacterial community of ducks (at least 80%). Before overfeeding,
      ileal samples were dominated by Bacilli, Clostridia, and Bacteroidia classes (>=
      70%), and cecal samples, by Bacteroidia and Clostridia classes (around 90%) in
      both Pekin and Muscovy ducks. The richness and diversity decreased in the ileum
      and increased in the ceca after overfeeding. Overfeeding triggers major changes
      in the ileum, whereas the ceca are less affected. Overfeeding increased the
      relative abundance of Clostridiaceae, Lactobacillaceae, Streptococcaceae, and
      Enterococcaceae families in the ileum, whereas genotype affects particularly
      three families: Lachnospiraceae, Bacteroidaceae, and Desulfovibrionaceae in the
      ceca.

PMID- 24102553
TI  - An enantioselective synthesis of voriconazole.
AB  - A new seven-step sequence to access voriconazole, a clinically used antifungal
      agent, was developed. The initial catalytic asymmetric cyanosilylation is the key
      to constructing the consecutive tetra- and trisubstituted stereogenic centers.
      The fluoropyrimidine unit frequently triggered unexpected side reactions, but
      careful amendment of the reaction sequence allowed for the concise
      enantioselective synthesis. 

PMID- 24102554
TI  - Comparison of components of biological variation between 3 equine
      thromboelastography assays.
AB  - BACKGROUND: There is a paucity of information about the analytical performance of
      thromboelastography (TEG) in horses, specifically concerning components of
      variation among different analytical methods. Such data may be obtained by nested
      analysis of repetitive standardized sampling of healthy individuals. OBJECTIVES:
      The objectives were (1) to assess the relative susceptibility to sources of
      preanalytical variation in a highly standardized setting, (2) to directly compare
      and evaluate the observed analytical variation, and (3) to assess the
      applicability of population-based reference intervals. METHODS: Blood was
      collected once from 20 healthy adult horses and weekly for 5 consecutive weeks
      from 8 healthy adult horses. TEG analyses were performed on citrated whole blood
      using nonactivated TEG and 2 TEG assays with human recombinant tissue factor (TF)
      or kaolin as activators. RESULTS: There were significant differences between
      nonactivated and activated assays for all measured parameters (P < .05). The
      intraindividual variation was significantly higher with the nonactivated assay
      compared with TF- and kaolin-activated protocols. Analytical variation was
      generally low and comparable for all 3 assays. Nonactivated TEG showed the
      highest degree of within-subject variation, TF-activated TEG (TF-TEG)
      intermediate and kaolin-activated TEG (K-TEG) the lowest degree of within-subject
      variation. CONCLUSIONS: Nonactivated TEG is more sensitive to preanalytical
      variation than both TF-TEG and K-TEG. Analytical variation was low and comparable
      for all assays, but not all parameters reached objective analytical goals. The
      results further indicate that population-based reference intervals can be readily
      applied to TF-TEG, but not to nonactivated or K-TEG, where critical difference
      may provide a better interpretation criterion.

PMID- 24102555
TI  - Nanobio interfaces: charge control of enzyme/inorganic interfaces for advanced
      biocatalysis.
AB  - Specific approaches to the rational design of nanobio interfaces for enzyme and
      protein binding to nanomaterials are vital for engineering advanced, functional
      nanobiomaterials for biocatalysis, sensing, and biomedical applications. This
      feature article presents an overview of our recent discoveries on structural,
      functional, and mechanistic details of how enzymes interact with inorganic
      nanomaterials and how they can be controlled in a systematic manner using alpha
      Zr(IV)phosphate (alpha-ZrP) as a model system. The interactions of a number of
      enzymes having a wide array of surface charges, sizes, and functional groups are
      investigated. Interactions are carefully controlled to screen unfavorable
      repulsions and enhance favorable interactions for high affinity, structure
      retention, and activity preservation. In specific cases, catalytic activities and
      substrate selectivities are improved over those of the pristine enzymes, and two
      examples of high activity near the boiling point of water have been demonstrated.
      Isothermal titration calorimetric studies indicated that enzyme binding is
      coupled to ion sequestration or release to or from the nanobio interface, and
      binding is controlled in a rational manner. We learned that (1) bound enzyme
      stabilities are improved by lowering the entropy of the denatured state; (2)
      maximal loadings are obtained by matching charge footprints of the enzyme and the
      nanomaterial surface; (3) binding affinities are improved by ion sequestration at
      the nanobio interface; and (4) maximal enzyme structure retention is obtained by
      biophilizing the nanobio interface with protein glues. The chemical and physical
      manipulations of the nanobio interface are significant not only for understanding
      the complex behaviors of enzymes at biological interfaces but also for desiging
      better functional nanobiomaterials for a wide variety of practical applications. 

PMID- 24102556
TI  - Asthma outcomes are poor among older adults with low health literacy.
AB  - OBJECTIVE: To examine the association of health literacy (HL) with asthma
      outcomes among older asthmatics. METHODS: The study included adults ages >=60
      with moderate to severe asthma in New York City and Chicago. We assessed asthma
      control with the Asthma Control Questionnaire (ACQ) and the percent predicted
      forced expiratory volume at 1 s (FEV1) by spirometry, hospitalizations and
      emergency department (ED) visits in the past 6 months, and quality of life. HL
      was assessed with the Short Test of Functional Health Literacy in Adults (S
      TOFHLA). Multivariate logistic regression models controlled for age, sex, race,
      income, general health and years with asthma. RESULTS: Among 433 individuals, 36%
      had low HL, 55% were over age 65, 38% were Hispanic and 22% were black. Poor
      asthma control was reported by 40% and 32% had FEV1 <70% of predicted; 9% had a
      hospital stay, 23% had an ED and 38% had poor quality of life. In multivariable
      analysis, individuals with low HL were more likely to have FEV1 <70% predicted
      (odds ratio [OR] 2.34, 95% confidence interval [CI] 1.39-3.94, p = 0.001),
      hospitalizations (OR 2.53, 95% CI 1.17-5.49, p = 0.02) and ED visits for asthma
      (OR 1.81, 95% CI 1.05-3.10, p = 0.03). There were no differences in self-reported
      asthma control and quality of life. CONCLUSIONS: Low HL is associated with poor
      asthma control by objective measure, and greater likelihood of ED visits and
      hospitalization. HL is a modifiable target for interventions to improve asthma
      outcomes in the elderly.

PMID- 24102557
TI  - Doxorubicin-induced death in tumour cells and cardiomyocytes: is autophagy the
      key to improving future clinical outcomes?
AB  - OBJECTIVES: Doxorubicin, a commonly used frontline chemotherapeutic agent for
      cancer, is not without side-effects. The original thinking that the drug causes
      necrosis in tumours has largely given way to its link with apoptosis over the
      past two decades. KEY FINDINGS: More recently, major biomarkers such as AMPK, p53
      and Bcl-2 have been identified as important to apoptosis induction by
      doxorubicin. It is Bcl-2 and its interaction with Beclin-1 that has refocussed
      research attention on doxorubicin, albeit this time for its ability to induce
      autophagy. Autophagy can be either anticancerous or procancerous however, so it
      is critical that the reasons for which cancer cells undergo this type of cell
      biological event be clearly identified for future exploitation. SUMMARY: Taking a
      step back from treating patients with large doses of doxorubicin, which causes
      toxicity to the heart amongst other organs, and further research with this drug's
      molecular signalling in not only neoplastic but normal cells, may indeed redefine
      the way doxorubicin is used clinically and potentially lead to better neoplastic
      disease management.

PMID- 24102558
TI  - Associations of season and region on objectively assessed physical activity and
      sedentary behaviour.
AB  - Seasonal and regional variation may influence physical activity (PA) patterns.
      These associations are in need of further investigation. The objective of the
      current study was to examine the association of season and region on objectively
      measured PA. The study was designed as a cross-sectional study with 1172
      participants living in Sweden. Data on PA were collected throughout a calendar
      year using accelerometry. Regions were categorised as south (Gotaland), central
      (Svealand) and north (Norrland). Outcome variables included accelerometer
      measured mean counts per minute, sedentary time and time in low intensity and
      moderate-intensity physical activity (MVPA) or greater. ANCOVA was used to
      determine the associations of season and region with PA, adjusting for sex, age,
      body mass index (BMI) and education. The results showed that during the Spring
      season more time was spent in MVPA than during the Autumn. For participants
      living in the south of Sweden, a significant trend for season was found for MVPA,
      with Spring having the highest MVPA (P = 0.025). Season had a borderline
      significant association with MVPA or higher intensity activities (P = 0.051). No
      significant effects of region or season on total PA, low-intensity PA and
      sedentary periods of time were observed. The results indicate that studies
      conducted in a population living in high latitudes, may not be significantly
      affected by seasonality or region when assessing PA.

PMID- 24102559
TI  - Factors influencing occupational therapy home visit practice: a qualitative
      study.
AB  - BACKGROUND: Home visits prior to discharge from hospital are an integral part of
      both occupational therapy practice and the discharge process. However, there is
      remarkably little understanding as to why they occur in practice and who is
      thought to best benefit from a home visit. The aims of this research were to
      explore occupational therapists' perceptions of home visits and to ascertain
      their clinical reasoning in respect of conducting home visits. Thematic analysis
      was used to analyse the data. RESULTS: The research revealed two different types
      of home visits: one with the patient and one without the patient. Both types
      aimed to enhance the discharge process. The key deciding factors for the chosen
      type of home visit were time issues and available resources. The therapist's
      justification for a home visit was also associated with the patient's living
      arrangements, impairments, and level of functioning. Occupational therapists
      rarely consulted patients about their preferred type of visit. CONCLUSION: This
      study is the first to identify therapists' reasoning between two types of home
      visits that occur in practice. Future trials are imperative to ascertain which
      visit is more effective in terms of both patient outcomes and cost effectiveness.

PMID- 24102560
TI  - The hooked element in the pes of turtles (Testudines): a global approach to
      exploring primary and secondary homology.
AB  - The hooked element in the pes of turtles was historically identified by most
      palaeontologists and embryologists as a modified fifth metatarsal, and often used
      as evidence to unite turtles with other reptiles with a hooked element. Some
      recent embryological studies, however, revealed that this element might represent
      an enlarged fifth distal tarsal. We herein provide extensive new myological and
      developmental observations on the hooked element of turtles, and re-evaluate its
      primary and secondary homology using all available lines of evidence. Digital
      count and timing of development are uninformative. However, extensive myological,
      embryological and topological data are consistent with the hypothesis that the
      hooked element of turtles represents a fusion of the fifth distal tarsal with the
      fifth metatarsal, but that the fifth distal tarsal dominates the hooked element
      in pleurodiran turtles, whereas the fifth metatarsal dominates the hooked element
      of cryptodiran turtles. The term 'ansulate bone' is proposed to refer to hooked
      elements that result from the fusion of these two bones. The available
      phylogenetic and fossil data are currently insufficient to clarify the secondary
      homology of hooked elements within Reptilia. 

PMID- 24102561
TI  - Automatic diagnosis of malaria based on complete circle-ellipse fitting search
      algorithm.
AB  - Diagnosis of malaria parasitemia from blood smears is a subjective and time
      consuming task for pathologists. The automatic diagnostic process will reduce the
      diagnostic time. Also, it can be worked as a second opinion for pathologists and
      may be useful in malaria screening. This study presents an automatic method for
      malaria diagnosis from thin blood smears. According to this fact that malaria
      life cycle is started by forming a ring around the parasite nucleus, the proposed
      approach is mainly based on curve fitting to detect parasite ring in the blood
      smear. The method is composed of six main phases: stain object extraction step,
      which extracts candidate objects that may be infected by malaria parasites. This
      phase includes stained pixel extraction step based on intensity and colour, and
      stained object segmentation by defining stained circle matching. Second step is
      preprocessing phase which makes use of nonlinear diffusion filtering. The process
      continues with detection of parasite nucleus from resulted image of previous step
      according to image intensity. Fourth step introduces a complete search process in
      which the circle search step identifies the direction and initial points for
      direct least-square ellipse fitting algorithm. Furthermore in the ellipse
      searching process, although parasite shape is completed undesired regions with
      high error value are removed and ellipse parameters are modified. Features are
      extracted from the parasite candidate region instead of whole candidate object in
      the fifth step. By employing this special feature extraction way, which is
      provided by special searching process, the necessity of employing clump splitting
      methods is removed. Also, defining stained circle matching process in the first
      step speeds up the whole procedure. Finally, a series of decision rules are
      applied on the extracted features to decide on the positivity or negativity of
      malaria parasite presence. The algorithm is applied on 26 digital images which
      are provided from thin blood smear films. The images are contained 1274 objects
      which may be infected by parasite or healthy. Applying the automatic
      identification of malaria on provided database showed a sensitivity of 82.28% and
      specificity of 98.02%. 

PMID- 24102562
TI  - Migration, mitochondria, and the yellow-rumped warbler.
AB  - Discordance between mitochondrial and nuclear DNA has been noted in many systems.
      Asymmetric introgression of mitochondria is a common cause of such discordances,
      although in most cases the drivers of introgression are unknown. In the yellow
      rumped warbler, evidence suggests that mtDNA from the eastern, myrtle warbler,
      has introgressed across much of the range of the western form, the Audubon's
      warbler. Within the southwestern United States myrtle mtDNA comes into contact
      with another clade that occurs in the Mexican black-fronted warbler. Both
      northern forms exhibit seasonal migration, whereas black-fronted warblers are
      nonmigratory. We investigated the link between mitochondrial introgression,
      mitochondrial function, and migration using novel genetic, isotopic, biochemical,
      and phenotypic data obtained from populations in the transition zone. Isotopes
      suggest the zone is coincident with a shift in migration, with individuals in the
      south being resident and populations further north becoming increasingly more
      migratory. Mitochondrial respiration in flight muscles demonstrates that myrtle
      type individuals have a significantly greater acceptor control ratio of
      mitochondria, suggesting it may be more metabolically efficient. To our knowledge
      this is the first time this type of intraspecific variation in mitochondrial
      respiration has been measured in wild birds and we discuss how such mitochondrial
      adaptations may have facilitated introgression. 

PMID- 24102564
TI  - Human platelet antigens - 2013.
AB  - To date, 33 human platelet alloantigens (HPAs) have been identified on six
      functionally important platelet glycoprotein (GP) complexes and have been
      implicated in alloimmune platelet disorders including foetal and neonatal
      alloimmune thrombocytopenia (FNAIT), posttransfusion purpura (PTP) and
      multitransfusion platelet refractoriness (MPR). The greatest number of recognized
      HPA (20 of 33) resides on the GPIIb/IIIa complex, which serves as the receptor
      for ligands important in mediating haemostasis and inflammation. These include
      HPA-1a, the most commonly implicated HPA in FNAIT and PTP in Caucasian
      populations. Other platelet GP complexes, GPIb/V/IX, GPIa/IIa and CD109, express
      the remaining 13 HPAs. Of the recognized HPAs, 12 occur as six serologically and
      genetically defined biallelic 'systems' where the -a form designates the higher
      frequency allele and the -b form, the lower. Twenty-one other HPAs are low
      frequency or rare antigens for which postulated higher frequency -a alleles have
      not yet been identified as antibody specificities. In addition to the HPA
      markers, platelets also express ABO and human leucocyte antigen (HLA) antigens;
      antibodies directed at the former are occasionally important in FNAIT, and to the
      latter, in MPR. 

PMID- 24102565
TI  - Huntington disease and Huntington disease-like in a case series from Brazil.
AB  - The aim of this study was to identify the relative frequency of Huntington's
      disease (HD) and HD-like (HDL) disorders HDL1, HDL2, spinocerebellar ataxia type
      2 (SCA2), SCA17, dentatorubral-pallidoluysian degeneration (DRPLA), benign
      hereditary chorea, neuroferritinopathy and chorea-acanthocytosis (CHAC), in a
      series of Brazilian families. Patients were recruited in seven centers if they or
      their relatives presented at least chorea, besides other findings. Molecular
      studies of HTT, ATXN2, TBP, ATN1, JPH3, FTL, NKX2-1/TITF1 and VPS13A genes were
      performed. A total of 104 families were ascertained from 2001 to 2012: 71
      families from South, 25 from Southeast and 8 from Northeast Brazil. There were 93
      HD, 4 HDL2 and 1 SCA2 families. Eleven of 104 index cases did not have a family
      history: 10 with HD. Clinical characteristics were similar between HD and non-HD
      cases. In HD, the median expanded (CAG)n (range) was 44 (40-81) units; R(2)
      between expanded HTT and age-at-onset (AO) was 0.55 (p=0.0001, Pearson). HDL2 was
      found in Rio de Janeiro (2 of 9 families) and Rio Grande do Sul states (2 of 68
      families). We detected HD in 89.4%, HDL2 in 3.8% and SCA2 in 1% of 104 Brazilian
      families. There were no cases of HDL1, SCA17, DRPLA, neuroferritinopathy, benign
      hereditary chorea or CHAC. Only six families (5.8%) remained without diagnosis.

PMID- 24102563
TI  - Evidence for phenylalanine zipper-mediated dimerization in the X-ray crystal
      structure of a magainin 2 analogue.
AB  - High-resolution structure elucidation has been challenging for the large group of
      host-defense peptides that form helices on or within membranes but do not
      manifest a strong folding propensity in aqueous solution. Here we report the
      crystal structure of an analogue of the widely studied host-defense peptide
      magainin 2. Magainin 2 (S8A, G13A, G18A) is a designed variant that displays
      enhanced antibacterial activity relative to the natural peptide. The crystal
      structure of magainin 2 (S8A, G13A, G18A), obtained for the racemic form,
      features a dimerization mode that has previously been proposed to play a role in
      the antibacterial activity of magainin 2 and related peptides. 

PMID- 24102566
TI  - Influence of mefenamic acid on the intestinal absorption and metabolism of three
      bioactive flavones in Radix Scutellariae and potential pharmacological impact.
AB  - CONTEXT: Mefenamic acid (MEF) and the dried root of Scutellaria baicalensis
      Georgi (Radix Scutellariae, RS) share a high possibility of combined medication
      to treat inflammation. OBJECTIVE: The present study investigates the impact of
      MEF on absorption/disposition of three major components in RS (baicalein, B;
      wogonin, W; oroxylin A, OA) and further pharmacological changes. MATERIALS AND
      METHODS: The apparent permeability (P(app)) and percentage of metabolism of B, W
      and OA at 10 MUMU were measured at the absence/presence of MEF (100 MUMU) in the
      Caco-2 cell monolayer model. A modified whole blood assay was employed to
      quantify prostaglandin E2 (PGE2) 4, 6 and 8 h post-oral administration with water
      suspension of MEF at 40 mg/kg and RS at 200 mg/kg. RESULTS: In the presence of
      MEF, Papp of B, W and OA were increased from 1.69 +/- 0.89 * 10-6, 1.57 +/- 0.10
      * 10-6 and 3.09 +/- 0.70 * 10-6 cm/sec to 5.24 +/- 0.27 * 10-6, 6.08 +/- 0.19 *
      10-6 and 4.13 +/- 0.38 * 10-6, whereas their percentage of metabolism was
      decreased from 72.75 +/- 2.44%, 73.27 +/- 3.25% and 89.84 +/- 2.99% to 21.11 +/-
      0.69%, 17.90 +/- 5.55% and 45.44 +/- 3.38%. PGE2 level was much lower in the co
      administration group (49.04 +/- 2.03 pg/ml) than in the MEF group (73.13 +/- 3.03
      pg/ml) or RS group (494.37 +/- 11.75 pg/ml) 4 h post MEF dosing, suggesting a
      synergic effect. DISCUSSION AND CONCLUSION: Co-administration of MEF and RS could
      induce potential alterations in their pharmacokinetic profiles and anti
      inflammatory effects.

PMID- 24102568
TI  - Functionalized low defect graphene nanoribbons and polyurethane composite film
      for improved gas barrier and mechanical performances.
AB  - A thermoplastic polyurethane (TPU) composite film containing hexadecyl
      functionalized low-defect graphene nanoribbons (HD-GNRs) was produced by solution
      casting. The HD-GNRs were well distributed within the polyurethane matrix,
      leading to phase separation of the TPU. Nitrogen gas effective diffusivity of TPU
      was decreased by 3 orders of magnitude with only 0.5 wt % HD-GNRs. The
      incorporation of HD-GNRs also improved the mechanical properties of the composite
      films, as predicted by the phase separation and indicated by tensile tests and
      dynamic mechanical analyses. The improved properties of the composite film could
      lead to potential applications in food packaging and lightweight mobile gas
      storage containers. 

PMID- 24102567
TI  - Impact of histidine residues on the transmembrane helices of viroporins.
AB  - Abstract The role of histidine in channel-forming transmembrane (TM) helices was
      investigated by comparing the TM helices from Virus protein 'u' (Vpu) and the M2
      proton channel. Both proteins are members of the viroporin family of small
      membrane proteins that exhibit ion channel activity, and have a single TM helix
      that is capable of forming oligomers. The TM helices from both proteins have a
      conserved tryptophan towards the C-terminus. Previously, alanine 18 of Vpu was
      mutated to histidine in order to artificially introduce the same HXXXW motif that
      is central to the proton channel activity of M2. Interestingly, the mutated Vpu
      TM resulted in an increase in helix tilt angle of 11 degrees  in lipid bilayers
      compared to the wild-type Vpu TM. Here, we find the reverse, when histidine 37 of
      the HXXXW motif in M2 was mutated to alanine, it decreased the helix tilt by 10
      degrees  from that of wild-type M2. The tilt change is independent of both the
      helix length and the presence of tryptophan. In addition, compared to wild-type
      M2, the H37A mutant displayed lowered sensitivity to proton concentration. We
      also found that the solvent accessibility of histidine-containing M2 is greater
      than without histidine. This suggests that the TM helix may increase the solvent
      exposure by changing its tilt angle in order to accommodate a polar/charged
      residue within the hydrophobic membrane region. The comparative results of M2,
      Vpu and their mutants demonstrated the significance of histidine in a
      transmembrane helix and the remarkable plasticity of the function and structure
      of ion channels stemming from changes at a single amino acid site. 

PMID- 24102569
TI  - Networking for philanthropy: increasing volunteer behavior via social networking
      sites.
AB  - Social networking sites (SNSs) provide a unique social venue to engage the young
      generation in philanthropy through their networking capabilities. An integrated
      model that incorporates social capital into the Theory of Reasoned Action is
      developed to explain volunteer behavior through social networks. As expected,
      volunteer behavior was predicted by volunteer intention, which was influenced by
      attitudes and subjective norms. In addition, social capital, an outcome of the
      extensive use of SNSs, was as an important driver of users' attitude and
      subjective norms toward volunteering via SNSs.

PMID- 24102570
TI  - Does Facebook promote self-interest? Enactment of indiscriminate one-to-many
      communication on online social networking sites decreases prosocial behavior.
AB  - Abstract Communication tools on social networking sites (SNSs) provide users with
      an efficient way to distribute information to the public and/or their friends
      simultaneously. In this article, we show that this kind of indiscriminate one-to
      many (i.e., monologue) communication, in which the diverse interests of
      recipients are not considered, may induce a tendency toward egocentrism that
      interferes with other-oriented concerns, resulting in a reduced inclination to
      display prosocial behavior. In Experiment 1, participants induced to post a
      public communication subsequently allocated less money to anonymous strangers in
      the dictator game than did control participants. In Experiment 2, participants
      directing a post about participation in an experiment to their Facebook friends
      volunteered to help code fewer data sheets than did controls. Moreover, an
      egocentric state was shown to mediate the relationship between indiscriminate one
      to-many communication and helping behavior. We provide the first demonstration
      that indiscriminate one-to-many communication on online social networks may be
      associated with a tendency toward self-interest. Our results suggest that the
      prevalence of monologue communication on SNSs may induce an egocentric tendency
      that undermines the likelihood of prosocial behavior. 

PMID- 24102571
TI  - Effects of dexmedetomidine on cerebral blood flow in critically ill patients with
      or without traumatic brain injury: a prospective controlled trial.
AB  - STUDY OBJECTIVE: To examine the effect of dexmedetomidine on CBF in critical ill
      patients with or without TBI. RESEARCH DESIGN: Prospective controlled trial
      (ISRCTN57998533). METHODS: Fifteen patients without TBI and 20 patients with TBI
      with a Glasgow Coma Scale score of 4-14 were assigned to CON or TBI groups,
      respectively. All patients received 1 MUg kg(-1) dexmedetomidine infused over 10
      minutes, followed by a 0.4 MUg kg(-1)h(-1) continuous infusion for 60 minutes.
      Blood pressure was maintained at the pre-sedation level with dopamine for all
      patients. The CBF and cerebral metabolic rate equivalent (CMRe) were measured
      before sedation and 70 minutes after dexmedetomidine administration. RESULTS:
      Dexmedetomidine administration significantly decreased CBF in patients of the CON
      group (difference = 3.3 ml s(-1), 95% confidence interval [CI] = 0.92-5.7 ml s(
      1), p = 0.008), without altering the CMRe and CMRe/CBF ratio. The dexmedetomidine
      induced change of CBF, CMRe and CMRe/CBF was not significant in the TBI group.
      The percentage of CBF reduction was greater in the CON group than in the TBI
      group (difference = 13.9%, 95% CI = 5.5-22.2%, p = 0.002). CONCLUSIONS:
      Dexmedetomidine may be used in patients with TBI without risk of affecting brain
      oxygenation.

PMID- 24102572
TI  - Sex-specific associations between thyrotropin and serum lipid profiles.
AB  - BACKGROUND: Population-based studies investigating the sex-specific association
      between thyrotropin (TSH) levels and serum lipid concentrations are scarce. We
      examined the association between TSH and total cholesterol, low-density
      lipoprotein (LDL) cholesterol, high-density lipoprotein (HDL) cholesterol, and
      triglycerides in men and women from the general population. Furthermore, the
      association with TSH outside and within the reference range and lipid levels was
      studied. METHODS: Individual data of 13,571 men and women without lipid
      medication of four population-based studies conducted in Western European adults
      were pooled for cross-sectional analyses. The association between TSH levels and
      lipid concentrations were analyzed by calculating sex-specific multivariable
      median regression models. RESULTS: In the pooled population, serum TSH levels
      were significantly positively associated with triglyceride values in men and with
      total cholesterol, LDL cholesterol, and triglyceride values in women. In the
      pooled male population, low serum TSH levels (<3.0 mIU/L) were significantly
      associated with lower total cholesterol, while high serum TSH levels (>= 3.0
      mIU/L) were associated with higher triglyceride values. In the pooled female
      population, low serum TSH levels were significantly associated with lower total
      cholesterol, LDL cholesterol, and HDL cholesterol. High TSH levels were
      associated with higher total cholesterol and LDL cholesterol in the pooled female
      population. In both sexes, serum TSH levels within the reference range (0.3-3.0
      mIU/L) were significantly positively associated with triglyceride concentrations.
      CONCLUSIONS: Increasing levels of TSH were associated with a less favorable lipid
      profile in both men and women from the general population. In both sexes, TSH
      levels within the reference range were significantly positively associated with
      triglyceride concentrations.

PMID- 24102573
TI  - Effect of chewing speed on energy expenditure in healthy subjects.
AB  - OBJECTIVE: The aim of the study was to investigate the effect of rate of chewing
      on energy expenditure in human subjects. MATERIALS AND METHODS: Fourteen healthy
      subjects (aged 18-24 years) within the normal range of BMI participated in a
      cross-over experiment consisting of two 6-min sessions of gum chewing, slow (~60
      cycles/min) and fast (~120 cycles/min) chewing. The resting energy expenditure
      (REE) and during gum chewing was measured using a ventilated hood connected to a
      gas analyzer system. The normality of data was explored using the Shapiro-Wilk
      test. The energy expenditure rate during chewing and the energy expenditure per
      chewing cycle were compared between the two chewing speeds using Wilcoxon signed
      ranks tests. RESULTS: The energy expenditure per chewing cycle during slow
      chewing (median 1.4, range 5.2 cal; mean 2.1+/-1.6 cal) was significantly higher
      than that during fast chewing (median 0.9, range 2.2 cal; mean 1.0+/-0.7 cal) (p
      < 0.005). However, the energy expenditure rate was not significantly different
      between the two chewing speeds (p > 0.05). CONCLUSIONS: The results of this study
      suggest that chewing at a slower speed could increase the energy expenditure per
      cycle and might affect the total daily energy expenditure.

PMID- 24102574
TI  - New insights into the biogeochemistry of extremely acidic environments revealed
      by a combined cultivation-based and culture-independent study of two stratified
      pit lakes.
AB  - The indigenous microbial communities of two extremely acidic, metal-rich
      stratified pit lakes, located in the Iberian Pyrite Belt (Spain), were
      identified, and their roles in mediating transformations of carbon, iron, and
      sulfur were confirmed. A combined cultivation-based and culture-independent
      approach was used to elucidate microbial communities at different depths and to
      examine the physiologies of isolates, which included representatives of at least
      one novel genus and several species of acidophilic Bacteria. Phosphate
      availability correlated with redox transformations of iron, and this (rather than
      solar radiation) dictated where primary production was concentrated. Carbon fixed
      and released as organic compounds by acidophilic phototrophs acted as electron
      donors for acidophilic heterotrophic prokaryotes, many of which catalyzed the
      dissimilatory reduction in ferric iron; the ferrous iron generated was re
      oxidized by chemolithotrophic acidophiles. Bacteria that catalyze redox
      transformations of sulfur were also identified, although these Bacteria appeared
      to be less abundant than the iron oxidizers/reducers. Primary production and
      microbial numbers were greatest, and biogeochemical transformation of carbon,
      iron, and sulfur, most intense, within a zone of c. 8-10 m depth, close to the
      chemocline, in both pit lakes. Archaea detected in sediments included two
      Thaumarchaeota clones, indicating that members of this recently described phylum
      can inhabit extremely acidic environments.

PMID- 24102575
TI  - Tuning the shape of mesoporous silica particles by alterations in parameter
      space: from rods to platelets.
AB  - The knowledge of how to control the pore size and morphology of separated
      mesoporous silica particles is crucial for optimizing their performance in
      applications, such as molecular sieves and drug delivery systems. In this work,
      we have systematically studied the effects of various synthesis parameters to
      gain a deeper understanding of how particle morphologies can be altered. It was
      found that the morphology for isolated particles of SBA-15 type, with unusually
      short and wide pores, could be altered from rods to platelets by variations in
      the NH4F concentration. The pore length is nearly constant (~300 nm) for the
      different morphologies, but the particle width is increasing from 200 nm to >3
      MUm when decreasing the amount of NH4F, and the pore size can be tuned between 10
      and 13 nm. Furthermore, other synthesis parameters such as heptane concentration,
      pH, silica precursor, and additions of ions have also been studied. The trend
      regarding particle width is independent of heptane concentration, at the same
      time as heptane increases the particle length up to a plateau value of ~500 nm.
      In all, parameters controlling particle width, length, and pore size have been
      separated in order to evaluate their function in the particle formation.
      Additionally, it was found that the formation time of the particles is strongly
      affected by the fluoride ion concentration, and a mechanism for particle
      formation for this system, where micelles transform from a foam, to multilamellar
      vesicles, and finally to cylindrical micelles, is suggested.

PMID- 24102576
TI  - Recovery of interleukin-17 production from interleukin-15-stimulated CD4+
      mononuclear cells in HIV-1-infected patients with sustained viral suppression.
AB  - Interleukin-17 (IL-17) is a pro-inflammatory cytokine that is mainly produced by
      CD4+ T cells. The role of Th17 during the human immunodeficiency virus (HIV)-1
      infection is still unclear, but HIV-1 infection can cause a preferential
      depletion of Th17 cells. It has been shown that IL-15 elicits IL-17 production
      from human peripheral blood mononuclear cells. We studied the effect of IL-15
      stimulation in vitro on IL-17 production from CD4+ mononuclear cells of HIV
      infected patients. We observed that IL-15 triggers, in a dose-dependent manner,
      IL-17 secretion. This effect was blocked by anti-IL-15 monoclonal antibody
      (P=0.01). Interestingly, IL-17 production was significantly lower in patients
      with detectable plasma viremia when compared with successfully treated HIV
      infected patients (P=0.02) and healthy controls, respectively (P<0.001). We also
      noticed a significant difference in IL-17 production between naive HIV-infected
      patients and patients with virological failure on combined antiretroviral therapy
      (cART) (P=0.02). Our results suggest that IL-15 can induce IL-17 production from
      peripheral CD4+ mononuclear cells of HIV-infected patients. Persistent HIV plasma
      viremia could cause a severe perturbation of IL-17 production from CD4+
      mononuclear cells. IL-17 production in HIV-infected patients could be recovered
      through a sustained suppression of the viral replication in the peripheral blood
      through cART. 

PMID- 24102577
TI  - Tailored vaccines targeting the elderly using whole inactivated influenza
      vaccines bearing cytokine immunomodulators.
AB  - Influenza and its complications disproportionately affect the elderly, leading to
      high morbidity and mortality in this ever-increasing population. Despite
      widespread vaccination efforts, the current influenza vaccines are less effective
      in the elderly; hence newer vaccine strategies are needed to improve their
      efficacy in this age group. We have previously shown that co-presentation of
      cytokines on the surface of inactivated influenza virus particles affords better
      protection from lethal homotypic viral challenge in young adult mice than
      conventional non-adjuvanted whole inactivated vaccine. Here, we determined the
      efficacy of these vaccine formulations in Balb/c mice "aged" to 17 months ("aged
      mice") along with the addition of a membrane-bound interleukin-12 (IL-12) vaccine
      formulation. Our investigations found that a single low-dose intramuscular
      vaccination with inactivated whole influenza vaccine co-presenting IL-12 was
      sufficient to provide enhanced protection from subsequent influenza challenge as
      compared with non-adjuvanted whole inactivated vaccine. Our results indicate that
      incorporation of cytokines such as IL-12 in a membrane-bound formulation in whole
      inactivated vaccine may provide a means to lower the vaccine dose while eliciting
      enhanced protective responses in the elderly, an age group that responds poorly
      to current vaccination regimens. 

PMID- 24102578
TI  - The role of the serum IL-33/sST2 axis and inflammatory cytokines in chronic
      obstructive pulmonary disease.
AB  - The IL-33/sST2 axis is associated with inflammation and cardiac stress. This
      study examined the roles of serum IL-33/sST2 and other inflammatory cytokines in
      chronic obstructive pulmonary disease (COPD) patients, with or without chronic
      cor pulmonale (CCP). The levels of serum IL-33 and sST2 in 36 COPD patients
      without CCP, 42 cases with CCP, and 37 healthy controls (HCs) were analyzed by
      enzyme-linked immunosorbent assay. The concentrations of serum TNF-alpha, IL
      1beta, IL-6, IL-8, IL-10, and IL-12 were analyzed by cytometric bead array. The
      pulmonary function was also determined. The levels of IL-33 in COPD patients were
      lower than in patients with CCP during the acute episode stage and HCs, and
      increased as patients transitioned into the stable phase, especially in patients
      whose modified medical research council scale values decreased. IL-33 levels were
      correlated positively with FEV1%pre, FVC%pre, FEF50%pre, and MMEF75/25%pre, while
      they correlated negatively with center airway resistance. There were no
      differences in the levels of sST2 among these groups. The concentrations of IL-6
      and IL-10 in COPD patients during acute episodes were significantly higher, and
      decreased during stable phases. IL-33 may be considered an important factor in
      the pathogenesis of COPD, and decreased IL-33 levels may be an indicator of the
      pulmonary function decline of COPD patients. 

PMID- 24102579
TI  - Ebola virus-like particles stimulate type I interferons and proinflammatory
      cytokine expression through the toll-like receptor and interferon signaling
      pathways.
AB  - Ebola viruses (EBOV) can cause severe hemorrhagic disease with high case fatality
      rates. Currently, no vaccines or therapeutics are approved for use in humans.
      Ebola virus-like particles (eVLP) comprising of virus protein (VP40),
      glycoprotein, and nucleoprotein protect rodents and nonhuman primates from lethal
      EBOV infection, representing as a candidate vaccine for EBOV infection. Previous
      reports have shown that eVLP stimulate the expression of proinflammatory
      cytokines in dendritic cells (DCs) and macrophages (MPhis) in vitro. However, the
      molecular mechanisms and signaling pathways through which eVLP induce innate
      immune responses remain obscure. In this study, we show that eVLP stimulate not
      only the expression of proinflammatory cytokines but also the expression of type
      I interferons (IFNs) and IFN-stimulated genes (ISGs) in murine bone marrow
      derived DCs (BMDCs) and MPhis. Our data indicate that eVLP trigger host responses
      through toll-like receptor (TLR) pathway utilizing 2 distinct adaptors, MyD88 and
      TRIF. More interestingly, eVLP activated the IFN signaling pathway by inducing a
      set of potent antiviral ISGs. Last, eVLP and synthetic adjuvants, Poly I:C and
      CpG DNA, cooperatively increased the expression of cytokines and ISGs. Further
      supporting this synergy, eVLP when administered together with Poly I:C conferred
      mice enhanced protection against EBOV infection. These results indicate that eVLP
      stimulate early innate immune responses through TLR and type I IFN signaling
      pathways to protect the host from EBOV infection. 

PMID- 24102580
TI  - The gingival biotype: measurement of soft and hard tissue dimensions - a
      radiographic morphometric study.
AB  - BACKGROUND: Gingival biotypes have been reported to influence the outcome of
      restorative therapies. The aim of this study was to evaluate the correlation of
      different morphometric parameters with the thickness of the buccal gingiva and
      alveolar bone at different apico-coronal levels. METHODS: In 60 periodontally
      healthy subjects, the central maxillary incisor was examined. Clinical parameters
      included the crown width/crown length ratio (CW/CL), gingival width (GW),
      gingival scallop (SC) and transparency of the periodontal probe through the
      gingival sulcus (TRAN). Gingival and alveolar bone dimensions were assessed on
      parallel profile radiographs. RESULTS: Crown width/crown length ratio was
      positively correlated with the thickness of the gingiva at the cementoenamel
      junction (G3) (r = 0.47) and to the thickness of the alveolar crest (A1) (r =
      0.46); whereas SC had a weak negative and GW had a moderate positive correlation
      with all radiographic measurements. TRAN had a stronger negative relation to the
      thickness at the free gingiva (r = -0.42) than to other tissue thicknesses. All
      gingival thickness values were correlated with A1 value. Multivariate models
      identified CW/CL and GW as significant predictors for G3 value, whereas CW/CL was
      a significant predictor for A1 value. CONCLUSION: Crown width/crown length ratio
      and GW could represent surrogate parameters to anticipate the gingival thickness
      at the cementoenamel junction, whereas CW/CL might also be an indicator for
      alveolar bone crest thickness. Periodontal probing has a limited prognostic value
      for these tissue dimensions.

PMID- 24102581
TI  - Human amniotic fluid stem cells suppress PBMC proliferation through IDO and IL-10
      dependent pathways.
AB  - Human amniotic fluid stem cells (hAFSCs) can be readily isolated from human
      amniotic fluid and display multi-differentiation potential and immunomodulatory
      properties. The mechanism of hAFSCs immunoregulation has not been defined. Here,
      we explore the immunomodulatory effects of hAFSCs derived from human amniotic
      fluid and evaluate the role of IL-10 and the tryptophan-catabolizing enzyme
      indoleamine 2,3-dioxygenase (IDO) in mediating the immunosuppressive actions of
      hAFSCs. Flow cytometry showed that hAFSCs were positive for the mesenchymal stem
      cell markers CD29, CD44, CD105, HLA-ABC, and more than 84% of the hAFSCs were
      positive for SSEA-4, which is a typical marker of embryonic stem cell (ESCs), and
      negative for HLA-DR. The RT-PCR and immunostaining results revealed that the
      multipotent stem cells expressed OCT-4, Nanog, CD44, SOX2 and SSEA-1. In vitro
      differentiation assays demonstrated that hAFSCs underwent osteogenic
      differentiation. We examined the immunomodulatory function of hAFSCs using a co
      culture system with phorbol 12-myristate 13-acetate (PMA) stimulated peripheral
      blood mononuclear cells (PBMCs). PBMC proliferation was suppressed by the hAFSCs
      in a dose-dependent manner. The inhibitory effect was caused by increased IL-10
      and IDO induction after co-culture. Neutralizing the IL-10 activity or blocking
      the function of IDO partially abolished the immunosuppressive action of the
      hAFSCs. In conclusion, these results suggest that the hAFSCs possess
      immunomodulatory properties, and IL-10 and IDO are involved in immunosuppression
      by hAFSCs. 

PMID- 24102582
TI  - Measuring kinematic changes of the foot using a gyro sensor during intense
      running.
AB  - Gyro sensor has been used to measure foot pronation during running with reliable
      results in previous studies, and the signals were not affected by the vibration
      of heel strikes. The purpose of this study was to observe the kinematic changes
      of the foot during intense running using a 3-axis gyro sensor. Fifteen male
      participants (average age: 24.5 +/- 1.7 years; mean height: 174.1 +/- 3.3 cm;
      mean body weight: 71.0 +/- 5.5 kg) were recruited in this study. Foot kinematic
      changes were observed in 30-min intense running protocols. The comparisons of the
      signals from gyro and motion analysis system were also performed to determine the
      accuracy of the gyro and showed positive results. In the main experiment, the
      ankle range of motion (ROM) in the frontal plane, measured using a motion system,
      showed a significant increase over time. Accordingly, peak angular velocity in
      the frontal plane also showed a significant increase. The correlation between
      ankle ROM and peak angular velocity in the frontal plane is significantly high (r
      = 0.975). Moreover, peak angular velocity in the frontal plane is also
      significantly correlated with both rate of perceived exertion (RPE) (r = 0.911)
      and heart rate (r = 0.960). This study concluded that an alarm system for foot
      kinematic changes related to running injuries can be built based on the peak
      angular velocity of the foot in the frontal plane.

PMID- 24102583
TI  - Mitochondrially targeted nitro-linoleate: a new tool for the study of
      cardioprotection.
AB  - BACKGROUND AND PURPOSE: Cardiac ischaemia-reperfusion (IR) injury remains a
      significant clinical problem with limited treatment options available. We
      previously showed that cardioprotection against IR injury by nitro-fatty acids,
      such as nitro-linoleate (LNO2 ), involves covalent modification of mitochondrial
      adenine nucleotide translocase 1 (ANT1). Thus, it was hypothesized that
      conjugation of LNO2 to the mitochondriotropic triphenylphosphonium (TPP(+) )
      moiety would enhance its protective properties. EXPERIMENTAL APPROACH: TPP(+) 
      LNO2 was synthesized from aminopropyl-TPP(+) and LNO2 , and characterized by
      direct infusion MS/MS. Its effects were assayed in primary cultures of
      cardiomyocytes from adult C57BL/6 mice and in mitochondria from these cells,
      exposed to simulated IR (SIR) conditions (oxygen and metabolite deprivation for
      1h followed by normal conditions for 1h) by measuring viability by LDH release
      and exclusion of Trypan blue. Nitro-alkylated mitochondrial proteins were also
      measured by Western blots, using antibodies to TPP(+) . KEY RESULTS: TPP(+) -LNO2
      protected cardiomyocytes from SIR injury more potently than the parent compound
      LNO2 . In addition, TPP(+) -LNO2 modified mitochondrial proteins, including ANT1,
      in a manner sensitive to the mitochondrial uncoupler carbonylcyanide-p
      trifluoromethoxyphenylhydrazone (FCCP) and the ANT1 inhibitor
      carboxyatractyloside. Similar protein nitro-alkylation was obtained in cells and
      in isolated mitochondria, indicating the cell membrane was not a significant
      barrier to TPP(+) -LNO2 . CONCLUSIONS AND IMPLICATIONS: Together, these results
      emphasize the importance of ANT1 as a target for the protective effects of LNO2 ,
      and suggest that TPP(+) -conjugated electrophilic lipid compounds may yield novel
      tools for the investigation of cardioprotection.

PMID- 24102584
TI  - Differentiated thyroid cancer: a new perspective with radiolabeled somatostatin
      analogues for imaging and treatment of patients.
AB  - BACKGROUND: The expression of somatostatin receptors (SSTR) in thyroid cells may
      offer the possibility to identify metastatic lesions and to select patients for
      peptide receptor radionuclide therapy (PRRT). We investigated (68)Ga-DOTATOC
      positron emission tomography/computed tomography (PET/CT) to select patients with
      progressive differentiated thyroid cancer (DTC) for PRRT as well as treatment
      response and toxicity in treated patients. METHODS: We enrolled 41 patients with
      progressive radioiodine-negative DTC (24 women and 17 men; mean age=54.3 years,
      median=59 years, range=19-78 years). In all patients, [(18)F]FDG-PET/CT was
      performed to determine recurrent disease with enhanced glucose metabolism, and
      (68)Ga-DOTATOC PET/CT was used to identify SSTR expression. Dosimetric evaluation
      was performed with (111)In-DOTATOC scintigraphy. Eleven patients were treated
      with PRRT receiving a fractionated injection of 1.5-3.7 GBq (90)Y
      DOTATOC/administration. Serial (68)Ga-DOTATOC PET/CT scans were performed in all
      treated patients to evaluate treatment response. Parameters provided by (68)Ga
      DOTATOC PET/CT were analyzed as potential therapeutic predictors to differentiate
      responding from nonresponding. In all treated patients, adverse events and
      toxicity were recorded. RESULTS: (68)Ga-DOTATOC PET/CT were positive in 24/41 of
      radioiodine-negative DTC patients. Based on the high expression of SSTR detected
      by (68)Ga-DOTATOC PET/CT, 13 patients were suitable for PRRT. Two out of 13
      patients were not treated due to the lack of fulfillment of other study inclusion
      criteria. PRRT induced disease control in 7/11 patients (two partial response and
      five stabilization) with a duration of response of 3.5-11.5 months. Objective
      response was associated with symptoms relief. Functional volume (FV) over time
      obtained by PET/CT was the only parameter demonstrating a significant difference
      between lesions responding and nonresponding to PRRT (p=0.001). Main PRRT adverse
      events were nausea, asthenia, and transient hematologic toxicity. One patient
      experienced permanent renal toxicity. CONCLUSIONS: In our series, SSTR imaging
      provided positive results in more than half of the cases with radioiodine
      negative DTC, and about one third of patients were eligible for PRRT. (68)Ga
      DOTATOC PET/CT seems a reliable tool both for patient selection and evaluation of
      treatment response. In our experience, FV determination over time seems to
      represent a reliable parameter to determine tumor response to PRRT, although
      further investigations are needed to better define its role.

PMID- 24102586
TI  - Hematologic reference intervals in Cynomolgus (Macaca fascicularis) monkeys.
AB  - BACKGROUND: Reference intervals are important aids for interpreting clinical
      pathology laboratory data especially in Cynomolgus monkey (Macaca fascicularis),
      the non-human primate species most widely used in biomedical research. The
      purpose of this study was to establish hematologic reference intervals for
      Cynomolgus according to the International Federation of Clinical Chemistry and
      Clinical and Laboratory Standards Institute guidelines using the databank at a
      primatology center. METHODS: Blood specimens from 272 healthy Cynomolgus imported
      from Mauritius, the Philippines and Vietnam, were analyzed. Reference intervals
      were established by nonparametric method. Effects of sex, age, body weight, and
      breeding origin were investigated. RESULTS: Hemoglobin, mean corpuscular
      hemoglobin, and mean corpuscular hemoglobin concentration decreased slightly and
      mean corpuscular volume increased slightly with age. Lower red blood cell
      concentration, hemoglobin, and hematocrit were observed in monkeys from the
      Philippines. CONCLUSIONS: These hematology reference intervals, established
      according to international recommendations, can be used in settings using similar
      animals and analyzers.

PMID- 24102585
TI  - Protein kinase C isoforms at the neuromuscular junction: localization and
      specific roles in neurotransmission and development.
AB  - The protein kinase C family (PKC) regulates a variety of neural functions
      including neurotransmitter release. The selective activation of a wide range of
      PKC isoforms in different cells and domains is likely to contribute to the
      functional diversity of PKC phosphorylating activity. In this review, we describe
      the isoform localization, phosphorylation function, regulation and signalling of
      the PKC family at the neuromuscular junction. Data show the involvement of the
      PKC family in several important functions at the neuromuscular junction and in
      particular in the maturation of the synapse and the modulation of
      neurotransmission in the adult. 

PMID- 24102587
TI  - Home Assessment of Person-Environment Interaction (HoPE): content validation
      process.
AB  - The purpose of this paper is to present the content validation, including a pilot
      test, of the Home Assessment of the Person-Environment Interaction (HoPE). The
      HoPE fills a gap for evaluating issues related to home adaptation. Using
      qualitative methods, a two-phase study was conducted: an expert consultation and
      a pilot test. The expert consultation was conducted via focus groups with
      occupational therapists (n = 20), and individual interviews with adults who had
      undergone home adaptation (n = 5). The pilot test was undertaken using a multiple
      case study design of four adults awaiting home adaptation. Data were audio
      recorded, transcribed, and analyzed using NUD.IST software. In phase 1, experts
      agreed with the content of HoPE and suggested minor changes. In phase 2, HoPE
      enabled occupational therapists to identify handicap-creating situations. After
      both phases, the final version of HoPE is more comprehensive than other current
      tools and addresses the complex experiences of clients with whom occupational
      therapists work which suggests a new approach for practice regarding home
      adaptation.

PMID- 24102588
TI  - Evidence-based practice in occupational therapy curricula.
AB  - The purpose of this study is to describe currently used educational strategies
      for teaching evidence-based practice (EBP) in entry-level master's degree
      occupational therapy programs in the United States. Fifty-eight entry-level
      occupational therapy program directors completed a survey. Results showed that
      occupational therapy programs consistently use a wide variety of EBP resources
      for teaching EBP including database searches, literature reviews, and the
      development of a research proposal. Less commonly used strategies include the use
      of case stories and journal clubs. The current study provides a baseline of
      existing strategies taught in entry level programs that may be built upon to
      gather more information about the content of EBP coursework, and determine ways
      to foster implementation of EBP in practice.

PMID- 24102589
TI  - Computer-based cognitive retraining for adults with chronic acquired brain
      injury: a pilot study.
AB  - This study evaluated the effectiveness of a computer-based cognitive retraining
      (CBCR) program on improving memory and attention deficits in individuals with a
      chronic acquired brain injury (ABI). Twelve adults with a chronic ABI
      demonstrating deficits in memory and attention were recruited from a convenience
      sample from the community. Using a quasi-experimental one-group pretest-posttest
      design, a significant improvement was found in both memory and attention scores
      postintervention using the cognitive screening tool. This study supported the
      effectiveness of CBCR programs in improving cognitive deficits in memory and
      attention in individuals with chronic ABI. Further research is recommended to
      validate these findings with a larger ABI population and to investigate transfer
      to improvement in occupational performance that supports daily living skills.

PMID- 24102590
TI  - Construct validity of the functionally simulated technology task: an exploratory
      study.
AB  - This study explored the construct validity of the Functional Simulated Technology
      Task (FSTT), online bill-pay version. The FSTT was administered to matched
      groups: persons with cognitive impairment and persons with no known cognitive
      impairment, established through the Montreal Cognitive Assessment (MoCA). Results
      indicated significance for construct validity by discriminating between the two
      groups. Results also indicated a good to excellent positive relationship between
      scores on the MoCA and the FSTT score areas of Outcome, Quality, Process, and
      Independence. The findings support the use of the FSTT to measure executive
      function using a simulated online bill-pay task.

PMID- 24102591
TI  - The DrivingHealth(r) Inventory as a clinical screening tool-assessment of face
      validity and acceptance.
AB  - To investigate the use and potential for patient acceptance of the
      DrivingHealth((r)) Inventory (DHI) in clinical practice, we administered the DHI
      to 360 community dwelling volunteers over age 50 at a Southeastern US
      rehabilitation hospital. Volunteers also completed surveys to document their
      health, driving habits, and impressions of the DHI. Volunteers reported strong
      agreement with statements that indicated that they believe the DHI measures
      abilities important for safe driving and that they would be willing to listen to
      advice about driving and safe mobility from medical professionals; however,
      responses to some items were more positive among drivers whose DHI results
      indicated no apparent loss of function that could impair driving. These results
      support the use of the DHI in clinical practice as a tool to raise awareness of
      factors that correlate to driving; however, further research will be necessary to
      investigate how the DHI may benefit diverse clinical populations. Experiences
      with using DHI as part of clinical practice are also discussed.

PMID- 24102594
TI  - Complete mitochondrial genome of a large-footed bat, Myotis macrodactylus
      (Vespertilionidae).
AB  - The complete mitochondrial genome was sequenced and characterized newly from a
      large-footed bat, Myotis macrodactylus (Vespertilionidae). The total length of
      the M. macrodactylus genome is 17,562 bp, with a base composition of 34.0% A,
      29.9% T, 23.0% C and 13.0% G. A short sequence of CATACG is repeated 60 times in
      D-loop region. Amino acid of M. macrodactylus was 92.7% similar to that of M.
      formosus. Nucleotide similarity was 86.6% in all the other gene regions except
      for D-loop with low 66.8% similarity.

PMID- 24102592
TI  - The validity of occupational performance assessments: a validity generalization
      meta-analysis.
AB  - The purpose of this meta-analysis was to determine sample weighted mean validity
      effect sizes for occupational performance assessments, and their generalizability
      from research to clinical settings. The bare-bones Validity Generalization (VG)
      guidelines developed by Hunter and Schmidt ( 2004 ) augmented by Maximum
      Likelihood (ML) procedures were used to complete the meta-analysis. The sample
      consisted of 27 studies in which convergent, divergent, and predictive validity
      estimates of occupational performance assessments were investigated. The mean
      coefficients of assessments validated in the studies constituting the sample for
      this meta-analysis ranged from medium to large. Further meta-analysis with
      complete dis-attenuation of observed mean validity coefficients is indicated.

PMID- 24102595
TI  - Unusual features of control region and a novel NADH 6 genes in mitochondrial
      genome of the finespot goby, Chaeturichthys stigmatias (Perciformes, Gobiidae).
AB  - In this article, we determined the complete mitogenome of finespot goby
      Chaeturichthys stigmatias with emphasis on the arranged gene order and gene
      feature with published Gobiidae species. The C. stigmatias mtDNA was 18,562 bp in
      length (56.94% AT), and comprised 37 genes (13 protein genes, 2 rRNAs and 22
      tRNAs) that was typical for mitochondrial genome of Gobiidae species. Unusually,
      the NADH 6 gene was very large in length compared with other Gobiidae species.
      Mitogenome of C. stigmatias had a long putative control region with high AT
      content (71.28%). Within this sequence, we determined repeat regions, the
      termination-associated sequence and the conserved sequence block for this region.
      The origin of L-strand replication in C. stigmatias was located in a cluster of
      five tRNA genes (WANCY). The conserved motif (5'-GCCGG-3') was also determined at
      the base of the stem in the tRNA-Cys gene. This study will provide a better
      understanding of Gobiidae mitogenomes and offer useful information for future
      studies concerning Gobiidae mitogenome evolution. 

PMID- 24102596
TI  - Complete mitochodrial genome of the redlip loach Leptobotia rubrilaris
      (Teleostei, Cypriniformes: Cobitidae).
AB  - In this study, the complete mitochondrial genome sequence of the Leptobotia
      rubrilaris has been obtained. The genome includes 13 protein-coding genes, 22
      tRNA genes, 2 rRNA genes and a non-coding control region with the total length of
      16,585 bp. The gene arrangement and composition were identical to other
      vertebrate. Most of the genes are encoded on heavy strand, except for eight tRNA
      and ND6 genes. The complete mitochondrial genome sequence of L. rubrilaris would
      contribute to better understand population genetics and protect its genetic
      diversity.

PMID- 24102597
TI  - Mitochondrial DNA diversity in the African American population.
AB  - Genetic polymorphism along mitochondrial DNA (mtDNA) defines population-specific
      signatures called mtDNA haplogroups. Estimation of mtDNA haplogroup distribution
      may be prone to errors, notably if the study sample is not drawn from a
      multicenter cohort. Here, we report on mtDNA diversity in a sample of African
      American individuals (n = 343) enrolled in a multicenter cohort. Sequencing of
      the hypervariable regions I and II of the D-loop control region showed that the
      most common mitochondrial variants are 73G, 146C, 150T, 152C, 189G, 16278T, and
      16311C. In agreement with the published data, we observed 17 common mtDNA
      haplogroups: L0, L1, L1b, L1c, L2, L2a, L2b, L2c, L2e, L3, L3b, L3d, L3e, L3f,
      L3h, L3x, and L4. The most commonly observed haplogroup is L2a (19.8%), followed
      by L1b (10.2%). Overall, the observed mtDNA haplogroup distribution in our study
      is similar to those published for the African American and the African
      populations. 

PMID- 24102598
TI  - Molecular detection of adulteration in chicken products based on mitochondrial
      12S rRNA gene.
AB  - The aim of this study is to detect the fraudulent in chicken products constitutes
      in order to protect consumers in Saudi Arabia from illegal substitutions. Two
      different approaches were used in this study, direct sequencing of specific
      fragments of amplified mitochondrial 12S rRNA gene in addition to species
      specific PCR primers for confirmation of the obtained Blast search results. The
      results showed that all processed chicken products were identified as chicken
      (Gallus gallus) by 90-98% homology depending on obtained sequence quality.
      Samples labeled with chicken luncheon (samples tested in this study) were
      identified as turkey meat (Meleagris gallopavo) by 98% homology, suggesting
      adulteration with inedible parts of turkey in chicken luncheon ingredients. The
      results showed also that not only chicken luncheon was mixed with inedible parts
      of turkey but also all chicken products tested in this study (chicken balls,
      chicken burger, chicken sausage and chicken mined meat) contained this turkey
      meat. Applying methods used in this study could be useful for accurate and rapid
      identification of commercial processed meat. 

PMID- 24102599
TI  - Mitochondrial DNA polymorphism in genes encoding ND1, COI and CYTB in canine
      malignant cancers.
AB  - The aim of the study was to identify DNA changes in mitochondrial gene fragments:
      NADH dehydrogenase subunit 1 (ND1), cytochrome c oxidase subunit I (COI) and
      cytochrome b (CYTB) in tumor tissue, normal tissue and blood, and to define their
      association with the tumor type in dogs. Molecular analysis included 144 tests in
      total. A functional effect of the non-synonymous protein coding SNP was
      predicted. The presence of polymorphisms in all tested gene fragments in
      individual tissues of dogs was observed. Heteroplasmic changes were found in ND1
      and CYTB in epithelioma glandulae sebacei and in CYTB in lymphoma
      centroblasticum. The results of in silico analysis show the impact of these
      alleles (COI: 507, ND1: 450, 216, CYTB: 748) on the functioning of proteins and
      thus their potential role in carcinogenesis. The possible harmful effects of
      changes in polypeptides in positions T193N, V98M, V118M and H196P were evaluated.
      It seems that polymorphisms occurring in cells can have a negative impact on
      functioning of proteins. This promotes disorders of the energy level in cells. 

PMID- 24102600
TI  - Complete mitochondrial genome sequence of the lined seahorse Hippocampus erectus
      Perry, 1810 (Gasterosteiformes: Syngnathidae).
AB  - The complete mitochondrial genome sequence of the lined seahorse Hippocampus
      erectus was first determined in this article. The total length of H. erectus
      mitogenome is 16,529 bp, which consists of 13 protein-coding genes, 22 tRNA and 2
      rRNA genes and 1 control region. The features of the H. erectus mitochondrial
      genome were similar to the typical vertebrates. The overall base composition of
      H. erectus is 31.8% A, 28.6% T, 24.3% C and 15.3% G, with a slight A + T rich
      feature (60.4%).

PMID- 24102601
TI  - Association study of mitochondrial DNA polymorphisms with type 2 diabetes in
      Tunisian population.
AB  - Mitochondrial DNA (mtDNA) variation may play an important role in the
      pathogenesis of type 2 diabetes (T2Ds). In this study, we aimed to explore
      whether mtDNA variants contribute to the susceptibility to T2Ds in a Tunisian
      population. The hypervariable region 1 (HVS1) of the mtDNA of 64 T2Ds patients
      and 77 healthy controls was amplified and sequenced. Statistical analysis was
      performed using the STATA program. Analysis of the total screened variants (N =
      88) from the HVS1 region showed no significant difference in the distribution of
      all polymorphisms between T2Ds and controls, except for the variant G16390A which
      was more frequent in T2Ds (15.9%) than in controls (5.4%) (p = 0.04). The
      association of G16390A was not detected after multivariate regression analysis.
      Similarly, analysis of the distribution of mitochondrial haplogroups within our
      dataset showed 18 distinct major haplogroups with no significant difference
      between T2Ds and controls. Except, the weakly association found for the G16390A
      variant, our results showed that none of the tested polymorphisms from the HVS1
      region have a major role in T2Ds pathogenesis in the studied Tunisian population
      even when taking into account the population stratification. 

PMID- 24102602
TI  - Characterization of complete mitochondrial genome of the skipper butterfly,
      Celaenorrhinus maculosus (Lepidoptera: Hesperiidae).
AB  - The skipper butterfly, Celaenorrhinus maculosus (Lepidoptera: Hesperiidae), is a
      small butterfly species that is widely distributed in Taiwan and mainland China.
      In this work, we sequenced and characterized the complete mitochondrial genome of
      the butterfly. The circular genome of 15,282 bp in length contains 13 protein
      coding genes, 22 transfer RNA genes, 2 ribosomal RNA genes and a non-coding AT
      rich region. Overall base composition of the complete mt genome was 33.97% A,
      39.90% T, 12.38% C and 7.75% G, with an AT bias of 79.87%. All protein-coding
      genes start with an ATN codon, and terminate with the typical stop codon TAA or a
      single T. The non-coding AT-rich region is 331 bp in length, including a 18 bp
      poly-T stretch and a microsatellite-like (TA)7 element. The genome sequence is
      useful for future studies of phylogenetics, molecular evolution, conservation
      genetics and agricultural control.

PMID- 24102603
TI  - Complete mitochondrial genome of the assassin bug Oncocephalus breviscutum
      (Hemiptera: Reduviidae).
AB  - The mitochondrial genome of an assassin bug, Oncocephalus breviscutum Reuter, is
      a typical circular DNA molecule of 15,984 bp with 37 genes and a large control
      region. The gene order is identical to that of the putative ancestral arrangement
      of insects. Twelve protein-coding genes start with ATN codon and ND4L uses GTG.
      All of the 22 tRNAs, ranging from 61 to 70 bp, have the clover-leaf structure
      except for the dihydrouridine (DHU) arm of trnS2 forms a simple loop. The control
      region is 1345 bp in length and includes six tandem repeats of three 31-nt and
      three 145-nt units.

PMID- 24102604
TI  - Complete mitochondrial genome of the Korean reeves's turtle Mauremys reevesii
      (Reptilia, Testudines, Geoemydidae).
AB  - The mitochondrial genome of Korean reeves's turtle Mauremys reevesii (Reptilia,
      Testudines, Geoemydidae) was studied. The complete mitochondrial genome sequence
      of M. reevesii was 16,784 bp in length and its gene arrangement pattern, gene
      content and gene organization is identical to those of geoemydids. The control
      region (CR) was located between the tRNA(Pro) and tRNA(Phe) genes and is 1253 bp
      in length. The typical conserved domains such as TAS and CSB-F, and CSB1, CSB2
      and CSB3 were identified in the CR of geoemydids.

PMID- 24102605
TI  - Complete mitochondrial genome of the amphidromous, red-tailed goby Sicyopterus
      lagocephalus (Pallas) (Teleostei, Gobiidae).
AB  - In this article, the complete mitogenome of the amphidromous, red-tailed goby,
      Sicyopterus lagocephalus has been amplified and sequenced by long polymerase
      chain reaction. This mitochondrial genome consists of 16,500 bp, with 13 protein
      coding genes, 2 ribosomal RNA genes, 22 transfer RNA genes, and a non-coding
      control region (CR), and its gene arrangement is identical to those of most
      vertebrates. The CR (841 bp) is located between tRNA(Pro) and tRNA(Phe). The
      overall base composition of the heavy strand is A, 28.9%; G, 16.4%; C, 28.3%; and
      T, 26.4%, with a slight AT bias of 55.3%. The complete mitogenomic data may
      provide more informative for phylogenetic approach for gobioid phylogeny
      especially for Sicydiine gobies. 

PMID- 24102606
TI  - The complete mitochondrial genome of Barbatula nuda (Cypriniformes:
      Nemacheilidae).
AB  - In this study, we cloned and sequenced the complete mitochondrial genome of
      Barbatula nuda. The genome was found to be 16,619 bp in size with a mostly
      conserved structural organization when compared with that of other teleost fish.
      It contained 37 genes (13 protein-coding genes, 22 transfer RNA genes, and 2
      ribosomal RNA genes) and 2 main non-coding regions (the control region and the
      origin of the light-strand replication). All protein-coding genes are initiated
      with ATG except for COX 1, which begin with GTG instead. However, the termination
      codons of 13 protein-coding genes varied with TAA, TA, T or TAG. The complete
      mitochondrial genome sequence is useful for phylogenetic analysis and studies of
      population genetics of B. nuda.

PMID- 24102607
TI  - Mitochondrial DNA sequence of the hybrid of Duroc (?) * [Landrace (?) * Yorshire
      (?)] pig.
AB  - Duroc (?) * [Landrace (?) * Yorshire (?)] (D * LY) pig is the popular hybrid pigs
      in order to make the most use of the heterosis in the world. In this study, the
      complete nucleotide sequence of D * LY pig mitochondrial genome was determined
      for the first time. Sequence analysis showed that the genome structure was in
      accordance with other pig breeds. It contained 22 tRNA genes, 2 ribosomal RNA
      genes, 13 protein-coding genes and 1 control region (D-loop region). The complete
      mitochondrial genome sequence of the D * LY pig provides an important data set
      for further study in genetic mechanism.

PMID- 24102608
TI  - Characterization of the complete mitochondrial genome of Oxygymnocypris stewartii
      (Cypriniformes: Cyprinidae).
AB  - The complete mitochondrial genome of Oxygymnocypris stewartii is 16,646 bp in
      size, containing 13 protein-coding genes, 22 transfer RNA genes, 2 ribosomal RNA
      genes and 2 non-coding regions (the control region and the origin of light-strand
      replication). The gene order of O. stewartii mitogenome is similar to those
      observed in most other vertebrates. The complete mitogenome sequence information
      of O. stewartii can provide useful data for further studies on phylogenetics,
      stock evaluation and conservation genetics.

PMID- 24102609
TI  - Complete mitochondrial genome sequences of two endangered Indian catfish species,
      Clarias batrachus and Pangasius pangasius.
AB  - Complete mitogenome sequences for Clarias batrachus (magur) and Pangasius
      pangasius (family Claridae and Pangasiidae, respectively) were generated, which
      were 16,511 and 16,476 bp, respectively. Both the mitogenomes contained 13
      protein-coding genes, 22 transfer RNAs, 2 ribosomal RNAs and 1 non-coding
      (control) region. The order of the genes was identical to that observed in most
      other vertebrates. The genome resource of complete mitogenome sequence of Indian
      catfish species generated during this study would be useful in phylogenetic
      studies.

PMID- 24102610
TI  - Weak hydrogen bonds formed by thiol groups in N-acetyl-(L)-cysteine and their
      response to the crystal structure distortion on increasing pressure.
AB  - The effect of hydrostatic pressure on single crystals of N-acetyl-l-cysteine was
      followed at multiple pressure points from 10(-4) to 6.2 GPa with a pressure step
      of 0.2-0.3 GPa by Raman spectroscopy and X-ray diffraction. Since in the crystals
      of N-acetyl-l-cysteine the thiol group is involved in intermolecular hydrogen
      bonds not as a donor only (bonds S-H...O) but also as an acceptor (bonds N
      H...S), increasing the pressure does not result in phase transitions. This makes
      a contrast with the polymorphs of l- and dl-cysteine, in which multiple phase
      transitions are observed already at relatively low hydrostatic pressures and are
      related to the changes in the conformation of the thiol side chains only weakly
      bound to the neighboring molecules in the structure and thus easily switching
      over the weak S-H...O and S-H...S hydrogen bonds. No phase transitions occur in N
      acetyl-l-cysteine with increasing pressure, and changes in cell parameters and
      volume vs pressure do not reveal any peculiar features. Nevertheless, a more
      detailed analysis of the changes in intermolecular distances, in particular, of
      the geometric parameters of the hydrogen bonds based on X-ray single crystal
      diffraction analysis, complemented by an equally detailed study of the positions
      of all the significant bands in Raman spectra, allowed us to study the fine
      details of subtle changes in the hydrogen bond network. Thus, as pressure
      increases, a continuous shift of the hydrogen atom of the thiol group from one
      acceptor (a carboxyl group) to another acceptor (a carbonyl group) is observed.
      Precise single-crystal X-ray diffraction and polarized Raman spectroscopy
      structural data reveal the formation of a bifurcated S-H...O hydrogen bond with
      increasing pressure starting with ~1.5 GPa. The analysis of the vibrational bands
      in Raman spectra has shown that different donor and acceptor groups start
      "feeling" the formation of the bifurcated S-H...O hydrogen bond in different
      pressure ranges. The results are discussed in relation to some of the previously
      published data on the effect of high pressure on the polymorphs of l-cysteine, dl
      cysteine, and glutathione, that show similarity with the effects reported here
      for N-acetyl-l-cysteine. The results obtained in this work allow one to suggest
      new models for the pressure-induced structural rearrangements in the whole family
      of cysteine-containing crystals. 

PMID- 24102611
TI  - Further validation of the psychometric properties of the Bowel Function Index for
      evaluating opioid-induced constipation (OIC).
AB  - OBJECTIVE: The BFI ? (Bowel Function Index) is a 3-item questionnaire for
      assessing opioid-induced constipation (OIC). The aim of this study was to
      contribute to the validation of the psychometric properties of the BFI by
      confirming a constipation threshold, and through correlation with other validated
      tools: KESS (Knowles Eccersley Scott Symptom) score and generic (12-Item Short
      Form Health Survey, SF-12) and specific (Patient Assessment of Constipation
      Quality of Life, PAC-QoL *) quality-of-life scores. METHODS: A survey on opioid
      requiring cancer-patients was carried out in France. A questionnaire was filled
      out for all patients that recorded their demographic characteristics, an
      assessment of their constipation using BFI and KESS scores, and included a self
      assessment of quality-of-life using PAC-QoL and SF-12. Correlation of BFI with
      KESS, PAC-QoL, and SF-12 was investigated. RESULTS: Five hundred and twenty
      patients participated in the entire data collection with no loss. BFI was shown
      to be statistically correlated (r = 0.571; p < 0.0001) with the KESS score and
      matches up with PAC-QoL and to a lesser extent with the SF-12 generic quality-of
      life questionnaire. A BFI threshold of 27-29 to discriminate constipated from non
      constipated patients was confirmed. KEY LIMITATIONS: This cross-sectional study
      in a selected population of cancer pain patients has validated the psychometric
      properties of the BFI. Further confirmation of the validity of the BFI could be
      sought through the use of longitudinal studies, and larger populations, such as
      non-cancer pain patients treated with opioids. CONCLUSION: This study contributes
      to the validation of the psychometric properties of the BFI. It confirms the BFI
      as an easy-to-use tool to assess constipation and its impact on quality-of-life
      in chronic pain patients.

PMID- 24102612
TI  - Synthesis and biological evaluation of direct thrombin inhibitors bearing 4
      (piperidin-1-yl)pyridine at the P1 position with potent anticoagulant activity.
AB  - The design and synthesis of a new class of nonpeptide direct thrombin inhibitors,
      built on the structure of 1-(pyridin-4-yl)piperidine-4-carboxamide, are
      described. Starting from a strongly basic 1-amidinopiperidine derivative (6)
      showing poor thrombin (fIIa) and factor Xa (fXa) inhibition activities, anti-fIIa
      activity and artificial membrane permeability were considerably improved by
      optimizing the basic P1 and the X-substituted phenyl P4 binding moieties.
      Structure-activity relationship studies, usefully complemented with molecular
      modeling results, led us to identify compound 13b, which showed excellent fIIa
      inhibition (Ki = 6 nM), weak anti-Xa activity (Ki = 5.64 MUM), and remarkable
      selectivity over other serine proteases (e.g., trypsin). Compound 13b showed in
      vitro anticoagulant activity in the low micromolar range and significant membrane
      permeability. In mice (ex vivo), 13b demonstrated anticoagulant effects at 2 h
      after oral dosing (100 mg.kg(-1)), with a significant 43% prolongation of the
      activated partial thromboplastin time (aPTT), over controls (P < 0.05). 

PMID- 24102613
TI  - Time-dependent decrement of dermal gadolinium deposits and significant
      improvement of skin symptoms in a patient with nephrogenic systemic fibrosis
      after temporary renal failure.
AB  - BACKGROUND: Nephrogenic systemic fibrosis (NSF) represents a rare fibrosing
      disorder occurring after administration of gadolinium-containing contrast agents
      during renal insufficiency. In order to prove the effect of gadolinium
      elimination on clinical signs, we identified and quantified gadolinium in skin
      biopsies of a 62-year-old patient with NSF with regard to improving skin lesions
      after recovery of renal function. METHODS: Gadolinium deposits were visualized
      and identified in NSF skin biopsies by light microscopy and transmission electron
      microscopy (EM) and by scanning EM. Inductively coupled plasma-mass spectrometry
      (ICPMS) was used for quantifying gadolinium concentration. RESULTS: Transmission
      EM studies revealed electron-dense material in connective matrix around blood
      vessels and inside lysosomes of histiocytes and fibroblasts. A remarkable
      reduction of gadolinium deposits was observed in transmission EM and scanning EM
      and confirmed by ICPMS in follow-up biopsies. After spontaneous recovery of renal
      function, his skin induration improved notably over the next 2 years.
      CONCLUSIONS: The reduction of clinical and histomorphological signs of NSF
      correlated with decreasing gadolinium concentration in skin biopsies within 3
      years. Our study suggests a possible pathogenetic mechanism of NSF including a
      chance for recovery after elimination of gadolinium and reduced histamine
      liberation by mast cells.

PMID- 24102614
TI  - Environmental and genetic control of brain and song structure in the zebra finch.
AB  - Birdsong is a classic example of a learned trait with cultural inheritance, with
      selection acting on trait expression. To understand how song responds to
      selection, it is vital to determine the extent to which variation in song
      learning and neuroanatomy is attributable to genetic variation, environmental
      conditions, or their interactions. Using a partial cross fostering design with an
      experimental stressor, we quantified the heritability of song structure and key
      brain nuclei in the song control system of the zebra finch and the genotype-by
      environment (G * E) interactions. Neuroanatomy and song structure both showed low
      levels of heritability and are unlikely to be under selection as indicators of
      genetic quality. HVC, in particular, was almost entirely under environmental
      control. G * E interaction was important for brain development and may provide a
      mechanism by which additive genetic variation is maintained, which in turn may
      promote sexual selection through female choice. Our study suggests that selection
      may act on the genes determining vocal learning, rather than directly on the
      underlying neuroanatomy, and emphasizes the fundamental importance of
      environmental conditions for vocal learning and neural development in songbirds. 

PMID- 24102615
TI  - In vitro-in vivo correlations for three different commercial immediate-release
      indapamide tablets.
AB  - The objective of this study was to develop and validate the in vitro-in vivo
      correlations (IVIVCs) of three commercially available immediate-release solid
      dosage forms of indapamide using drug dissolution/absorption simulating system
      (DDASS). The in vitro dissolution profiles of three brands of immediate-release
      tablets were obtained using the USP I basket method and DDASS. A single-dose,
      three-way, crossover pharmacokinetic study for the tablets was carried out in six
      beagle dogs. Correlation models were developed for each immediate release
      formulation using cumulative percentage dissolved/eluted (Fd) versus cumulative
      percentage absorbed (Fa) and cumulative percentage permeated (Fp) versus
      cumulative percentage absorbed (Fa). Prediction errors were estimated for the
      Cmax and AUC to determine the validity of the correlation. Level A IVIVCs were
      established for the three brands between in vitro (dissolution and permeation)
      data from DDASS and in vivo data from dogs. Predicted plasma concentrations of
      each commercial brand were obtained from the dissolution and permeation profile
      data using the correlation models. A percent prediction error of <15% for the
      Cmax and AUC was found for all of the formulations, which validates the internal
      predictability of the IVIVC models obtained. However, the IVIVC models from the
      permeation data failed to predict the AUC. The results support the use of in
      vitro dissolution and permeation data as a surrogate for bioequivalent study and
      suggest that DDASS can be applied as an in vitro system for the validated-IVIVC
      development of BCS II solid drug formulations.

PMID- 24102616
TI  - The impact of manufacturing variables on in vitro release of clobetasol 17
      propionate from pilot scale cream formulations.
AB  - OBJECTIVES: The purpose of the study was to evaluate the effect of different
      homogenization speeds and times, anchor speeds and cooling times on the viscosity
      and cumulative % clobetasol 17-propionate released per unit area at 72 h from
      pilot scale cream formulations. A 2(4) full factorial central composite design
      for four independent variables were investigated. MATERIALS AND METHODS: Thirty
      pilot scale batches of cream formulations were manufactured using a Wintech(r)
      cream/ointment plant. The viscosity and in vitro release of CP were monitored and
      compared to an innovator product that is commercially available on the South
      African market, namely, Dermovate(r) cream. RESULTS AND DISCUSSION: Contour and
      three-dimensional response surface plots were produced and the viscosity and
      cumulative % CP released per unit area at 72 h were found to be primarily
      dependent on the homogenization and anchor speeds. An increase in the
      homogenization and anchor speeds appeared to exhibit a synergistic effect on the
      resultant viscosity of the cream whereas an antagonistic effect was observed for
      the in vitro release of CP from the experimental cream formulations. The in vitro
      release profiles were best fitted to a Higuchi model and diffusion proved to be
      the dominant mechanism of drug release that was confirmed by use of the Korsmeyer
      Peppas model. CONCLUSION: The research was further validated and confirmed by the
      high prognostic ability of response surface methodology (RSM) with a resultant
      mean percentage error of (+/-SD) 0.17 +/- 0.093 suggesting that RSM may be an
      efficient tool for the development and optimization of topical formulations.

PMID- 24102617
TI  - Preparation of concentrated stable fenofibrate suspensions via liquid antisolvent
      precipitation.
AB  - A major challenge in achieving size stability for relatively high concentration
      of fine particles from poorly water-soluble drug fenofibrate (FNB) is addressed
      through T-mixing based liquid antisolvent precipitation in the presence of
      ultrasonication and judicious use of stabilizers. Multiple stabilizers were
      screened in a batch mode prior to their continuous formation via T-mixing. In
      both cases, the stable suspensions maintained their size after 2 days of storage
      at room temperature, with the smallest particle size of d50: ~1.2 um was achieved
      through a combination of HPMC with SDS or PF-68. The influence of processing
      parameters, such as sonication energy, sonication probe insert depth and
      solvent/antisolvent flow rate, on the particle size distribution (PSD) in T
      mixing were investigated, to identify optimum processing conditions. Optimal
      operating and formulation conditions also allowed increase in the drug loading
      from 0.32% to 4% (w/v), while keeping the median size 2.5 um. Interestingly, the
      primary particles observed in the SEM were spherical and under 100 nm in
      diameter, indicating agglomeration. It was shown that the stabilized particles
      could be centrifuged and did not show size growth upon resuspension, allowing for
      increase in the drug loading up to 27% (w/v), which is a significant novel
      outcome.

PMID- 24102618
TI  - Optimization of experimental parameters to determine the jetting regimes in
      electrohydrodynamic printing.
AB  - The harmony of ink and printing method is of importance in producing on-demand
      droplets and jets of ink. Many factors including the material properties, the
      processing conditions, and the nozzle geometry affect the printing quality. In
      electrohydrodynamic (EHD) printing where droplets or jets are generated by the
      electrostatic force, the physical as well as the electrical properties of the
      fluid should be taken into account to achieve the desired performance. In this
      study, a systematic approach was suggested for finding the processing windows of
      the EHD printing. Six dimensionless parameters were organized and applied to the
      printing system of ethanol/terpineol mixtures. On the basis of the correlation of
      the dimensionless voltage and the charge relaxation length, the jet diameter of
      cone-jet mode was characterized, and the semicone angle was compared with the
      theoretical Taylor angle. In addition, the ratio of electric normal force and
      electric tangential force on the charged surface of the Taylor cone was
      recommended as a parameter that determines the degree of cone-jet stability. The
      cone-jet became more stable as this ratio got smaller. This approach was a
      systematic and effective way of obtaining the Taylor cone of the cone-jet mode
      and evaluating the jetting stability. The control of the inks with optimized
      experimental parameters by this method will improve the jetting performance in
      EHD inkjet printing. 

PMID- 24102619
TI  - Cholesterol metabolism is a potential therapeutic target for Rett syndrome.

PMID- 24102620
TI  - ZnO microrods to nanowalled microtubes: optimization using simple fluorescence
      microscopy and enhanced photocatalytic properties.
AB  - ZnO microtubes (MTs) of nanoscale wall thickness were prepared by synthesis of
      ZnO microrods (MRs) followed by etching the MRs to form MTs. ZnO MRs were
      synthesized by a simple solution growth method using zinc chloride and hexamine
      as precursors. Using KOH, ZnO MRs are etched into ZnO MTs. ZnO MTs were
      characterized by fluorescence microscopy (FM), X-ray diffraction, scanning
      electron microscopy, UV-Vis and photoluminescence spectroscopy. ZnO MTs have a
      diameter of ~600 nm, wall thickness of 30-40 nm and length of ~7 MUm. The
      influence of the KOH concentration and etching time on ZnO MRs for the formation
      of the ZnO MTs were studied. The formation of nanowalled ZnO tubes from ZnO MRs
      is optimized by simple and inexpensive FM imaging. FM was utilized as a tool to
      observe the changes in optical properties on change in morphology from ZnO MRs to
      MTs. FM images reveal that at low KOH concentration (0.125 M) the tubes were not
      completely etched whereas at higher concentration (0.375 M) the tube walls were
      damaged. Etchant concentration (0.125 M) and etching time of 12 h were found to
      be the optimized parameters for the realization of ZnO MTs using FM analysis. ZnO
      MTs were tested as the catalyst for the photodegradation of the methylene blue
      dye. The result shows that the photodegradation efficiency of the tubes is twice
      as fast as compared to that of rods. 

PMID- 24102622
TI  - The mini-mental state examination and the Montreal Cognitive Assessment after
      traumatic brain injury: an early predictive study.
AB  - PRIMARY OBJECTIVE: To compare results on the Montreal Cognitive Assessment (MoCA)
      to those on the Mini-Mental State Examination (MMSE) in patients with traumatic
      brain injury (TBI) and to predict the outcome at discharge from the acute care
      setting. RESEARCH DESIGN: A retrospective study. METHODS AND PROCEDURES: The MoCA
      and the MMSE were administered to 214 patients with TBI during their acute care
      hospitalization in a Level I trauma centre. Outcome was measured with the
      Disability Rating Scale (DRS). MAIN OUTCOMES AND RESULTS: A linear regression
      determined that the MoCA, the MMSE, TBI severity, education level and presence of
      diffuse injuries predicted 57% of the total variability of the DRS scores. The
      model without the MMSE had a R2 of 53.7% and the model without the MoCA had a R2
      of 55.0%. The models without the MMSE or the MoCA had a R2 of 24.9%. CONCLUSIONS:
      These results indicated that the MoCA and the MMSE function as similar predictors
      of the DRS at discharge.

PMID- 24102621
TI  - Caspase cleavage of GFAP produces an assembly-compromised proteolytic fragment
      that promotes filament aggregation.
AB  - IF (intermediate filament) proteins can be cleaved by caspases to generate
      proapoptotic fragments as shown for desmin. These fragments can also cause
      filament aggregation. The hypothesis is that disease-causing mutations in IF
      proteins and their subsequent characteristic histopathological aggregates could
      involve caspases. GFAP (glial fibrillary acidic protein), a closely related IF
      protein expressed mainly in astrocytes, is also a putative caspase substrate.
      Mutations in GFAP cause AxD (Alexander disease). The overexpression of wild-type
      or mutant GFAP promotes cytoplasmic aggregate formation, with caspase activation
      and GFAP proteolysis. In this study, we report that GFAP is cleaved specifically
      by caspase 6 at VELD225 in its L12 linker domain in vitro. Caspase cleavage of
      GFAP at Asp225 produces two major cleavage products. While the C-GFAP (C-terminal
      GFAP) is unable to assemble into filaments, the N-GFAP (N-terminal GFAP) forms
      filamentous structures that are variable in width and prone to aggregation. The
      effect of N-GFAP is dominant, thus affecting normal filament assembly in a way
      that promotes filament aggregation. Transient transfection of N-GFAP into a human
      astrocytoma cell line induces the formation of cytoplasmic aggregates, which also
      disrupt the endogenous GFAP networks. In addition, we generated a neo-epitope
      antibody that recognizes caspase-cleaved but not the intact GFAP. Using this
      antibody, we demonstrate the presence of the caspase-generated GFAP fragment in
      transfected cells expressing a disease-causing mutant GFAP and in two mouse
      models of AxD. These findings suggest that caspase-mediated GFAP proteolysis may
      be a common event in the context of both the GFAP mutation and excess.

PMID- 24102623
TI  - Growth inhibition and apoptosis of Ehrlich ascites carcinoma cells by the
      methanol extract of Eucalyptus camaldulensis.
AB  - CONTEXT: Eucalyptus camaldulensis Dehnh. (Myrtaceae) is a tall evergreen tree
      found commonly in Bangladesh. Its use in traditional folk medicine for the
      treatment of various health complications are well known. OBJECTIVE: To explore
      the in vivo antitumor effect of Eucalyptus camaldulensis stem bark methanol
      extract (ME) against Ehrlich's ascites carcinoma (EAC) in Swiss albino mice.
      MATERIALS AND METHODS: The antitumor activity of ME was studied by determining
      viable tumor cell count, recording tumor weight and survival time, observing
      morphological changes and nuclear damage of EAC cells, and estimating
      hematological as well as biochemical parameters of experimental mice (25, 50 and
      100 mg/kg/day for 5 d, i.p.). RESULTS: ME showed 96% (p < 0.001) cell growth
      inhibition and reduced tumor burden significantly (81.4%; p < 0.01) when compared
      with control mice. It also increased the lifespan of EAC-bearing mice
      significantly (71.36%; p < 0.01). It also restored the altered hematological and
      biochemical parameters towards normal level. The high LD50 value (1120 mg/kg) of
      ME indicated its low host toxic effects. ME-treated EAC cells showed membrane
      blebbing, chromatin condensation, nuclear fragmentation (apoptotic features) in
      Hoechst 33342 staining under fluorescence microscope. The DNA profile in agarose
      gel (1.5%) electrophoresis also confirmed that ME caused EAC cell death by
      apoptosis. DISCUSSION AND CONCLUSION: Results showed that ME exhibits strong
      anticancer activity through apoptosis and stimulation of host immunity. Thus, E.
      camaldulensis may be considered as a promising resource in cancer chemotherapy.

PMID- 24102624
TI  - Direct asymmetric alpha-allylation of alpha-branched aldehydes by two catalytic
      systems with an achiral Pd complex and a chiral primary alpha-amino acid.
AB  - Direct alpha-allylation of alpha-branched aldehydes was successfully carried out
      with a readily available allyl ester by combined use of two catalytic systems:
      Tsuji-Trost allylation reaction with an achiral palladium complex and enamine
      catalysis with a chiral primary alpha-amino acid. A quaternary carbon stereogenic
      center was constructed stereoselectively to give various 2,2-disubstituted pent-4
      enals in good yields with high enantioselectivity. 

PMID- 24102625
TI  - Commercial DNA extraction kits impact observed microbial community composition in
      permafrost samples.
AB  - The total community genomic DNA (gDNA) from permafrost was extracted using four
      commercial DNA extraction kits. The gDNAs were compared using quantitative real
      time PCR (qPCR) targeting 16S rRNA genes and bacterial diversity analyses
      obtained via 454 pyrosequencing of the 16S rRNA (V3 region) amplified in single
      or nested PCR. The FastDNA((r)) SPIN (FDS) Kit provided the highest gDNA yields
      and 16S rRNA gene concentrations, followed by MoBio PowerSoil((r)) (PS) and MoBio
      PowerLyzerTM (PL) kits. The lowest gDNA yields and 16S rRNA gene concentrations
      were from the Meta-G-NomeTM (MGN) DNA Isolation Kit. Bacterial phyla identified
      in all DNA extracts were similar to that found in other soils and were dominated
      by Actinobacteria, Firmicutes, Gemmatimonadetes, Proteobacteria, and
      Acidobacteria. Weighted UniFrac and statistical analyses indicated that bacterial
      community compositions derived from FDS, PS, and PL extracts were similar to each
      other. However, the bacterial community structure from the MGN extracts differed
      from other kits exhibiting higher proportions of easily lysed beta- and gamma
      Proteobacteria and lower proportions of Actinobacteria and Methylocystaceae
      important in carbon cycling. These results indicate that gDNA yields differ
      between the extraction kits, but reproducible bacterial community structure
      analysis may be accomplished using gDNAs from the three bead-beating lysis
      extraction kits.

PMID- 24102626
TI  - Death preparedness: a concept analysis.
AB  - AIM: To report analysis of the concept death preparedness in the context of end
      of-life shared decisions and communication. BACKGROUND: Forty percent of older
      people require decision-making and communication in the final days of life.
      Elaborate defence mechanisms have yielded a public consciousness that no longer
      passively views death acceptance, but instead has a defensive orientation of
      preparedness. The term 'death preparedness' depicts this death attitude. DESIGN:
      Concept analysis. DATA SOURCES: Data were collected over 3 months in 2013. A
      series of searches of scholarly peer-reviewed literature published in English
      were conducted of multiple databases. Specific keywords included such phrases as:
      death acceptance, death avoidance, death rejection, death preparedness,
      resolution of life, breaking bad news and readiness to die. METHODS: Walker and
      Avant's method was chosen as a deductive method to distinguish between the
      defining attributes of death preparedness and its relevant attributes. RESULTS:
      Death preparedness involves a transition of facilitated communication with a
      healthcare provider that leads to awareness and/or acceptance of end of life, as
      evidenced by an implementation of a plan. An appraisal of attitudes towards death
      and one's mortality precedes the concept, followed by an improved quality of
      death and dignity at end of life. CONCLUSION: The concept of death preparedness
      in the process of dying should be the focus of research to explore areas to
      improve advanced directive planning and acceptance of palliation for chronic
      health conditions.

PMID- 24102627
TI  - Polymorphisms in the MT-ATP6 and MT-CYB genes in in vitro fertilization failure.
AB  - The purpose of this study was to investigate whether fertilization failure after
      in vitro fertilization could be explained by polymorphisms in MT-ATP6 and MT-CYB
      genes. We performed a prospective comparative study of 111 fresh IVF cycles in
      Han Chinese between July 2011 and February 2013. Human sperm mitochondrial DNA
      (mtDNA) variants in the MT-CYB and MT-ATP6 genes were screened by polymerase
      chain reaction (PCR) and direct sequencing. Forty-six couples had low
      fertilization rates (< or =30%) or total fertilization failure, and 65 controls
      with normal fertilization. One unreported point mutation (A15472G) was found in
      this study. There were 7 and 3 polymorphic sites in the MT-ATP6 and MT-CYB,
      respectively. Interestingly, the frequencies of points 8701 and 15301 homozygous
      variants in study group were significantly higher than those in control group.
      However, the frequencies of the points 8701, 9075 and 15,301 heterozygous
      variants in study group were significantly lower than those in control group
      (4.35% versus 16.92%, 15.22% versus 32.31% and 6.52% versus 33.84%, respectively,
      p < 0.05). In addition, the frequency in subjects harboring A8701G and G15301A
      variants in study group was significantly higher than that in control group
      (63.04% versus 33.85%, p < 0.05). This study suggests that, in part,
      polymorphisms in the MT-ATP6 and MT-CYB genes may contribute to the unexpected
      fertilization failure.

PMID- 24102630
TI  - Association of vitamin D receptor gene polymorphisms with chronic and aggressive
      periodontitis in Jordanian patients.
AB  - Vitamin D acts through binding with vitamin D receptor (VDR) and is responsible
      for regulating bone metabolism and mineralization; it also suppresses the immune
      system. The aim of this study was to investigate if VDR gene polymorphisms are
      associated with chronic periodontitis (CP) and aggressive periodontitis (AgP) in
      a Jordanian population. A total of 99 patients with CP, 63 patients with AgP, and
      126 controls were genotyped using PCR-restriction fragment length polymorphism
      (RFLP) for BsmI, ApaI, and TaqI single nucleotide polymorphisms (SNPs). The
      association was determined after correcting for confounding factors using
      multivariate logistic regression analysis. Estimation of haplotype frequencies
      was carried out using the EH program, and haplotypes were constructed using the
      phase 2.1 program. After correcting for confounding factors, multivariate
      logistic regression analysis revealed that inheritance of the BsmI bb genotype or
      the ApaI aa genotype was associated with increased risk of developing CP (OR =
      2.4 and OR = 3.4, respectively) but with reduced risk of developing AgP (OR = 0.4
      and OR = 0.3, respectively). This was further supported by association of the ba
      haplotype with CP but not with AgP. This study supports an association of VDR
      gene polymorphisms with CP and AgP in a Jordanian population; however, the
      pattern of association was different between the two diseases.

PMID- 24102631
TI  - Absence of intraocular infections after hematopoietic stem cell transplantation
      at a single center: the experience with current preventive regimens.
AB  - PURPOSE: To investigate the prevalence of intraocular infections after allogeneic
      stem cell transplantation (allo-SCT). METHODS: The study design was a single
      institutional retrospective noncomparative cohort of 135 consecutive patients in
      2006 and 2007 who underwent allo-SCT for hematological malignancy. The primary
      outcome was the development of intraocular infections after allo-SCT and
      secondary outcome consisted of development of other ocular disorders during
      follow-up. RESULTS: The most frequent ocular sequel to allo-SCT included ocular
      graft-versus-host disease (GvHD), which developed in 37/135 patients (27%).
      Intraocular infection occurred in 1 of 135 patients (0.7%). This patient
      developed infectious chorioretinitis together with osteomyelitis, endocarditis,
      and brain abscess with fungus Scedosporium and was successfully treated with a
      combination of voriconazole, amphotericine B, and surgical interventions. Viral
      and/or bacterial intraocular infections were not observed at all. CONCLUSIONS:
      Intraocular infections after allo-SCT are currently uncommon due to systematic
      use of preemptive treatment regimens, frequent controls, and early treatment of
      systemic infections.

PMID- 24102632
TI  - Leukocytoclastic vasculitis masking chronic vascular changes in previously
      undiagnosed erythropoietic protoporphyria.
AB  - A 31-year old man presented with swelling and purpura of the dorsum of the hands
      following sun exposure. There was a preceding lifelong history of
      photosensitivity, but this episode, which occurred after the recent commencement
      of oral iron therapy, and after recent alcohol ingestion, was much more severe
      than any preceding episode. Skin biopsy performed 48 h after the onset of
      symptoms showed features consistent with the early stages of leukocytoclastic
      vasculitis. Direct immunofluorescence showed homogeneous thick staining of the
      vessel walls with IgG, IgM and IgA, together with abundant perivascular
      fibrinogen. A subsequent periodic acid-Schiff (PAS) stain on the skin biopsy
      revealed thickening of the walls of dermal vessels, which was not discernible in
      routinely stained (hematoxylin/eosin) sections. The diagnosis of erythropoietic
      protoporphyria (EPP) was confirmed by significantly elevated erythrocyte
      protoporphyrin levels and positive plasma fluorimetry. The diagnosis of porphyria
      may have been missed by routine skin microscopy if not for the additional
      information provided by clinical history, direct immunofluorescence and PAS
      stain. The pathogenesis and histopathology of acute and chronic vascular changes
      in EPP are reviewed.

PMID- 24102633
TI  - Kinematic analysis of the backstroke start: differences between backstroke
      specialists and non-specialists.
AB  - The purpose of this study was to clarify factors to perform the hole-entry
      technique in the backstroke start. A total of 16 well-trained Japanese
      competitive swimmers were divided into two groups (backstroke specialists and non
      specialists) to compare their backstroke start motions. Their backstroke motions
      were videotaped, and two-dimensional co-ordinates for the swimmers were obtained
      from the video images using direct linear transformation methods. A non-paired t
      test and Mann-Whitney U-test were used to analyse the statistical difference of
      the kinematic variables between the groups. Backstroke specialists showed a
      significantly shorter 5 m time (P = 0.009, effect size = -1.54), a significantly
      higher position of the toe (P = 0.010, effect size = 1.47) at signal and of the
      hip at toe-off (P = 0.002, effect size = 1.94), a significantly larger hip joint
      angle at toe-off (P = 0.007, effect size = 1.60) and a significantly higher
      angular velocities of the hip joints (45-85%; P < 0.05) for the normalised time
      as compared to that of non-specialists. An earlier initiation of the extension
      and the maintenance of a higher extension speed at the hip joints were important
      factors in achieving an arched-back posture, which facilitated and water entrance
      with a small entry range.

PMID- 24102634
TI  - Cardiac stability at differing levels of temporal analysis in panic disorder,
      post-traumatic stress disorder, and healthy controls.
AB  - The panic disorder (PD) literature provides evidence for both physiologic
      rigidity and instability as pathognomonic features of this disorder. This
      ambiguity may be a result of viewing PD at differential levels of temporal
      analysis. We assessed cardiac variability across three levels of temporal scale
      in PD patients, post-traumatic stress disorder (PTSD) patients, and healthy
      controls. Sixteen healthy controls, 14 PD patients, 23 PTSD patients, and 16 PTSD
      + PD patients presented for a polysomnogram. Differences were assessed in
      respiratory sinus arrhythmia (RSA), autoregressive stability of heart rate (HR),
      and the number of nonspecific accelerations in HR over the night. No differences
      in RSA were found between groups; however, PD patients exhibited significantly
      lower autoregressive HR stability, and all patients had significantly more HR
      accelerations than controls. These data reinforce prior findings demonstrating
      physiologic instability in PD and indicate that prior equivocalities regarding
      physiologic variability in PD may be due to limited temporal scaling of
      measurements. 

PMID- 24102635
TI  - Identification of genes for melatonin synthetic enzymes in 'Red Fuji' apple
      (Malus domestica Borkh.cv.Red) and their expression and melatonin production
      during fruit development.
AB  - Melatonin is present in many edible fruits; however, the presence of melatonin in
      apple has not previously been reported. In this study, the genes for melatonin
      synthetic enzymes including tryptophan decarboxylase, tryptamine 5-hydroxylase
      (T5H), arylalkylamine N-acetyltransferase, and N-acetylserotonin
      methyltransferase were identified in 'Red Fuji' apple. Each gene has several
      homologous genes. Sequence analysis shows that these genes have little homology
      with those of animals and they only have limited homology with known genes of
      rice melatonin synthetic enzymes. Multiple origins of melatonin synthetic genes
      during the evolution are expected. The expression of these genes is fully
      coordinated with melatonin production in apple development. Melatonin levels in
      apple exhibit an inverse relationship with the content of malondialdehyde, a
      product of lipid peroxidation. Two major melatonin synthetic peaks appeared on
      July 17 and on October 8 in both unbagged and bagged apple samples. At the
      periods mentioned above, apples experienced rapid expansion and increased
      respiration. These episodes significantly elevate reactive oxygen species
      production in the apple. Current data further confirmed that melatonin produced
      in apple was used to neutralize the toxic oxidants and protect the developing
      apple against oxidative stress. 

PMID- 24102636
TI  - Insights into direct nose to brain delivery: current status and future
      perspective.
AB  - Now a day's intranasal (i.n) drug delivery is emerging as a reliable method to
      bypass the blood-brain barrier (BBB) and deliver a wide range of therapeutic
      agents including both small and large molecules, growth factors, viral vectors
      and even stem cells to the brain and has shown therapeutic effects in both
      animals and humans. This route involves the olfactory or trigeminal nerve systems
      which initiate in the brain and terminate in the nasal cavity at the olfactory
      neuroepithelium or respiratory epithelium. They are the only externally exposed
      portions of the central nervous system (CNS) and therefore represent the most
      direct method of noninvasive entry into the brain. This approach has been
      primarily used to explore therapeutic avenues for neurological diseases. The
      potential for treatment possibilities with olfactory transfer of drugs will
      increase as more effective formulations and delivery devices are developed.
      Recently, the apomorphine hydrochloride dry powders have been developed for i.n.
      delivery (Apomorphine nasal, Lyonase technology, Britannia Pharmaceuticals,
      Surrey, UK). The results of clinical trial Phase III suggested that the prepared
      formulation had clinical effect equivalent to subcutaneously administered
      apomorphine. In coming years, intranasal delivery of drugs will demand more
      complex and automated delivery devices to ensure accurate and repeatable dosing.
      Thus, new efforts are needed to make this noninvasive route of delivery more
      efficient and popular, and it is also predicted that in future a range of
      intranasal products will be used in diagnosis as well as treatment of CNS
      diseases. This review will embark the existing evidence of nose-to-brain
      transport. It also provides insights into the most relevant pre-clinical studies
      of direct nose-brain delivery and delivery devices which will provide relative
      success of intranasal delivery system. We have, herein, outlined the relevant
      aspects of CNS drugs given intranasally to direct the brain in treating CNS
      disorders like Alzheimer's disease, depression, migraine, schizophrenia, etc.

PMID- 24102637
TI  - The impact of age on the diagnosis and therapy of myelodysplastic syndromes:
      results from a retrospective multicenter analysis in Germany.
AB  - Myelodysplastic syndromes (MDS) is a disease of predominantly elderly patients
      with a median age of >70 yrs. However, data on the management of these patients
      outside of clinical trials are scarce. To assess patterns of MDS management in
      routine patient care with regard to the impact of age, we conducted a
      multicenter, representative survey of MDS health services in Germany. Data of 269
      patients treated at 57 institutions were collected from preplanned chart reviews
      and were analyzed retrospectively. At diagnosis, median age was 70 yrs, 50% of
      patients had a Karnofsky index (KI) of 90%, and 12% had a comorbidity index >= 3
      according to Sorror et al. (J Clin Oncol, 25, 2007, 4246). Cytogenetic analysis
      and International Prognostic Scoring System (IPSS) risk assessment were performed
      significantly less frequently in patients >75 yrs than in patients <= 75 yrs (P <
      0.001 and P = 0.019). In bivariate analysis, potential predictors for performing
      IPSS risk assessment were age <= 75 yrs (y/n, P = 0.019), diagnosis at a
      university hospital (y/n, P = 0.001), WHO subtypes RCUD (y/n, P = 0.028), RARS
      (y/n, P = 0.002), or RAEB II (y/n, P = 0.037). Patients <= 75 yrs were more
      likely to receive active therapies (i.e., chemotherapy, immunomodulatory therapy,
      or epigenetic therapy) than patients >75 yrs (51% vs. 37%, P = 0.007). In
      bivariate analysis age <= 75 yrs (y/n, P = 0.007) was a significant predictor for
      active treatment with no correlation with the other predictors [IPSS risk score
      int-2 or high (y/n, P = 0.005), WHO subtypes RCUD (y/n, P < 0.001), RCMD (y/n, P
      = 0.003), RAEB II (y/n, P < 0.001), or CMML I (y/n, P = 0.020)]. This survey
      confirms the impact of age on the thoroughness of MDS diagnosis and the decision
      for active treatment. As cytogenetic analysis and risk assessment are essential
      for the choice of appropriate therapy, elderly patients in particular may not be
      receiving adequate treatment.

PMID- 24102638
TI  - Fabrication of nitric oxide-releasing porous polyurethane membranes-coated needle
      type implantable glucose biosensors.
AB  - The active release of pharmaceutical agents and the use of porous sensor
      membranes represent the two most promising strategies for addressing the poor
      tissue biocompatibility of implantable glucose biosensors. Herein, we describe
      the combination of these approaches to create nitric oxide (NO)-releasing porous
      fiber mat-modified sensor membranes. An electrospinning method was used to
      directly modify needle-type glucose biosensors with the NO donor-loaded fibers.
      The resulting NO-releasing fiber mat (540 +/- 139 nm fiber diameter, 94.1 +/-
      3.7% porosity) released ~100 nmol of NO per mg of polyurethane over 6 h while
      maintaining a porous structure without leaching of the NO donor, even in serum.
      The porous fiber membrane did not influence the analytical performance of the
      biosensor when <=50 MUm thick.

PMID- 24102639
TI  - An investigation into the effect of the structure of bile salt aggregates on the
      binding interactions and ESIHT dynamics of curcumin: a photophysical approach to
      probe bile salt aggregates as a potential drug carrier.
AB  - This work demonstrates the utilization of bile salt aggregates as a potential
      biological host system for studying the binding interactions and dynamics of the
      poorly-water-soluble drug curcumin by means of photophysical techniques. We found
      that the level of degradation of curcumin is greatly suppressed upon
      encapsulation into the nanocavities of three different bile salt aggregates.
      However, NaTC aggregates are more effective to suppress the level of degradation
      of curcumin than NaCh and NaDC aggregates. We also report the modulation of the
      photophysical and dynamical properties of curcumin into the nanocavities of bile
      salt aggregates using steady-state and time-resolved fluorescence spectroscopy.
      The reduced level of interaction of curcumin with water upon incorporation into
      the different binding sites of bile salt aggregates results in an enhanced
      fluorescence intensity along with the blue shift in the emission maxima of
      curcumin. However, the observation of higher fluorescence quantum yield as well
      as longer fluorescence lifetime in NaTC aggregates compared to that in NaCh and
      NaDC aggregates clearly indicates a more effective decrease in the excited-state
      intramolecular hydrogen atom transfer (ESIHT) mediated nonradiative deactivation
      of curcumin by the interaction with the anionic headgroup of NaTC. The binding
      and location of curcumin into the bile salt aggregates has been further confirmed
      from the steady-state fluorescence anisotropy measurements. In addition, we have
      shown the effect of addition of salt on the photophysical properties of curcumin
      in the confined environments of bile salt aggregates. Our results indicate that
      on addition of salt the time scale of ESIHT process of curcumin in bile salt
      aggregates is markedly increased. 

PMID- 24102640
TI  - Proteomics and the stressful life of lactobacilli.
AB  - Lactobacilli occupy specific ecological niches, where they represent a major
      component of foods, human and animal microbial communities. Employing these
      bacteria in industrial fermentations or for human health benefits exposes them to
      certain life-threatening conditions where their ability to adapt plays a key role
      in their survival and continued microbial activity. Since the postgenomic era
      began, proteomics has become the first choice among research approaches available
      for environmental adaptation and stress response investigators. The latest
      developments in the applications of proteomics to understand physiological
      changes in Lactobacillus species under harsh conditions are remarkable. 

PMID- 24102641
TI  - Paranuclear dot-like cytokeratin MNF116 positivity in cutaneous myoepithelioma.

PMID- 24102642
TI  - Transthoracic echocardiographic detection of pulmonary valve involvement in
      Loeffler's endocarditis.
AB  - We are describing pulmonary valve involvement with thickening and stenosis
      detected by two-dimensional transthoracic echocardiography in an adult presenting
      with Loeffler's endocarditis. To our knowledge, this has not been described
      previously. Complete regression of the lesions occurred with corticosteroid
      therapy. Tricuspid valve thickening and stenosis and thickening and thrombus
      formation in the right ventricle also present initially disappeared completely
      with therapy. 

PMID- 24102643
TI  - The calmodulin-like protein CML43 functions as a salicylic-acid-inducible root
      specific Ca(2+) sensor in Arabidopsis.
AB  - Many signalling pathways in plants are regulated by the second messenger calcium
      (Ca(2+)). In the standard model, Ca(2+)-sensor proteins, such as CaM
      (calmodulin), detect Ca(2+) signals and subsequently regulate downstream targets
      to advance the signal transduction cascade. In addition to CaM, plants possess
      many CMLs (CaM-like proteins) that are predicted to function as Ca(2+) sensors,
      but which remain largely uncharacterized. In the present study, we examined the
      biochemical properties, subcellular localization and tissue-specific distribution
      of Arabidopsis CML43. Our data indicate that CML43 displays characteristics
      typical of Ca(2+) sensors, including high-affinity Ca(2+) binding, conformational
      changes upon Ca(2+) binding that expose hydrophobic regions and stabilization of
      structure in the presence of Mg(2+) or Ca(2+). In vivo localization analysis
      demonstrates that CML43 resides in cytosolic and nuclear compartments. Transgenic
      plants expressing a CML43:GUS (beta-glucoronidase) promoter reporter gene
      revealed that CML43 promoter activity is restricted almost exclusively to root
      tips under normal growth conditions. GUS reporter activity in these transgenic
      plants was strongly increased when exposed to the defence compound SA (salicylic
      acid). Furthermore, immunoblot analysis revealed that the CML43 protein
      accumulates following treatment with SA. Collectively, our findings suggest that
      CML43 functions as a Ca(2+) sensor in root tips during both normal growth and
      plant immune response.

PMID- 24102644
TI  - Visual functions in amblyopia as determinants of response to treatment.
AB  - PURPOSE: To describe the visual functions in amblyopia as determinants of
      response to treatment. METHODS: Sixty-nine patients with unilateral and bilateral
      amblyopia (114 amblyopic eyes) 3 to 15 years old (mean age: 8.80 +/- 2.9 years),
      40 males (58%) and 29 females (42%), were included in this study. All patients
      were treated by conventional occlusion 6 hours per day for mild to moderate
      amblyopia (visual acuity 0.70 or better) and full-time for 4 weeks followed by 6
      hours per day for severe amblyopia (visual acuity 0.8 or worse). During
      occlusion, near activities requiring hand-eye coordination were advised. The
      follow-up examination was done at 3 and 6 months. Improvement in visual acuity
      was evaluated on the logMAR chart and correlated with the visual functions.
      Statistical analysis was done using Wilcoxon rank sum test (Mann-Whitney U test)
      and Kruskal-Wallis analysis. RESULTS: There was a statistically significant
      association of poor contrast sensitivity with the grade of amblyopia (P < .001).
      The grade of amblyopia (P < .01), accommodation (P < .01), stereopsis (P = .01),
      and mesopic visual acuity (P < .03) were found to have a correlation with
      response to amblyopia therapy. CONCLUSIONS: The grade of amblyopia (initial
      visual acuity) and accommodation are strong determinants of response to amblyopia
      therapy, whereas stereopsis and mesopic visual acuity have some value as
      determinants.

PMID- 24102645
TI  - Cis-regulatory underpinnings of human GLI3 expression in embryonic craniofacial
      structures and internal organs.
AB  - The zinc finger transcription factor Gli3 is an important mediator of Sonic
      hedgehog (Shh) signaling. During early embryonic development Gli3 participates in
      patterning and growth of the central nervous system, face, skeleton, limb, tooth
      and gut. Precise regulation of the temporal and spatial expression of Gli3 is
      crucial for the proper specification of these structures in mammals and other
      vertebrates. Previously we reported a set of human intronic cis-regulators
      controlling almost the entire known repertoire of endogenous Gli3 expression in
      mouse neural tube and limbs. However, the genetic underpinning of GLI3 expression
      in other embryonic domains such as craniofacial structures and internal organs
      remain elusive. Here we demonstrate in a transgenic mice assay the potential of a
      subset of human/fish conserved non-coding sequences (CNEs) residing within GLI3
      intronic intervals to induce reporter gene expression at known regions of
      endogenous Gli3 transcription in embryonic domains other than central nervous
      system (CNS) and limbs. Highly specific reporter expression was observed in
      craniofacial structures, eye, gut, and genitourinary system. Moreover, the
      comparison of expression patterns directed by these intronic cis-acting
      regulatory elements in mouse and zebrafish embryos suggests that in accordance
      with sequence conservation, the target site specificity of a subset of these
      elements remains preserved among these two lineages. Taken together with our
      recent investigations, it is proposed here that during vertebrate evolution the
      Gli3 expression control acquired multiple, independently acting, intronic
      enhancers for spatiotemporal patterning of CNS, limbs, craniofacial structures
      and internal organs. 

PMID- 24102646
TI  - Metabolic flux is a determinant of the evolutionary rates of enzyme-encoding
      genes.
AB  - Relationships between evolutionary rates and gene properties on a genomic,
      functional, pathway, or system level are being explored to unravel the principles
      of the evolutionary process. In particular, functional network properties have
      been analyzed to recognize the constraints they may impose on the evolutionary
      fate of genes. Here we took as a case study the core metabolic network in human
      erythrocytes and we analyzed the relationship between the evolutionary rates of
      its genes and the metabolic flux distribution throughout it. We found that
      metabolic flux correlates with the ratio of nonsynonymous to synonymous
      substitution rates. Genes encoding enzymes that carry high fluxes have been more
      constrained in their evolution, while purifying selection is more relaxed in
      genes encoding enzymes carrying low metabolic fluxes. These results demonstrate
      the importance of considering the dynamical functioning of gene networks when
      assessing the action of selection on system-level properties. 

PMID- 24102647
TI  - On a vector space representation in genetic algorithms for sensor scheduling in
      wireless sensor networks.
AB  - Recent works raised the hypothesis that the assignment of a geometry to the
      decision variable space of a combinatorial problem could be useful both for
      providing meaningful descriptions of the fitness landscape and for supporting the
      systematic construction of evolutionary operators (the geometric operators) that
      make a consistent usage of the space geometric properties in the search for
      problem optima. This paper introduces some new geometric operators that
      constitute the realization of searches along the combinatorial space versions of
      the geometric entities descent directions and subspaces. The new geometric
      operators are stated in the specific context of the wireless sensor network
      dynamic coverage and connectivity problem (WSN-DCCP). A genetic algorithm (GA) is
      developed for the WSN-DCCP using the proposed operators, being compared with a
      formulation based on integer linear programming (ILP) which is solved with exact
      methods. That ILP formulation adopts a proxy objective function based on the
      minimization of energy consumption in the network, in order to approximate the
      objective of network lifetime maximization, and a greedy approach for dealing
      with the system's dynamics. To the authors' knowledge, the proposed GA is the
      first algorithm to outperform the lifetime of networks as synthesized by the ILP
      formulation, also running in much smaller computational times for large
      instances. 

PMID- 24102648
TI  - Distribution of dopamine transporter immunoreactive fibers in the human
      amygdaloid complex.
AB  - The nuclei of the human amygdaloid complex can be distinguished from each other
      on the basis of their cytoarchitecture, chemistry and connections, all of which
      process the information needed for the different functions (ranging from
      attention to memory and emotion) of the amygdala. This complex receives
      dopaminergic input that exerts modulatory effects over its intrinsic network and
      is critical for reward-related learning and fear conditioning. To determine the
      specific distribution of the dopaminergic input through the different nuclei and
      nuclear subdivisions of this structure we used stereological tools to quantify
      the fibers containing the dopamine transporter (used to signal the dopaminergic
      phenotype) in post-mortem samples from control individuals. Dopaminergic axons
      targeted every nucleus of the amygdaloid complex, and the density of dopamine
      transporter-containing axons varied considerably among its nuclear groups. The
      central group showed the greatest density of dopamine transporter-positive
      fibers, more than double the density of the basolateral group, the second most
      densely innervated structure. The dopamine transporter-positive innervation is
      very scant in the corticomedial group. The density of dopamine transporter
      positive fibers did not vary among the nuclei of the basolateral group - i.e.
      basal, lateral and accessory basal nuclei - although there were significant
      density gradients among the subdivisions of these nuclei. These detailed
      quantitative data on dopamine transporter-positive innervation in the human
      amygdaloid complex can offer a useful reference in future studies aimed at
      analysing putative dysfunctions of this system in diseases involving brain
      dopamine, such as certain anxiety disorders, Parkinson's disease and
      schizophrenia. 

PMID- 24102650
TI  - Swiss Nursing Homes Human Resources Project (SHURP): protocol of an observational
      study.
AB  - AIM: To explore the relationships among various nursing homes characteristics
      including work environment, careworker outcomes and resident outcomes in Swiss
      nursing homes. BACKGROUND: In Switzerland, a growing number of older people live
      in nursing homes. Although research has addressed the issue of quality of nursing
      care in such facilities, few have integrated a range of interrelated factors that
      may influence the quality and safety of residential care. The Swiss Nursing Homes
      Human Resources Project will comprehensively assess key organizational factors,
      their interrelationships and the associations between these factors and
      careworker and resident outcomes. DESIGN: Cross-sectional design. METHODS: Three
      year multi-centre study (2011-2013) including a representative sample of
      approximately 160 nursing homes across the three language regions in Switzerland.
      Survey data will come from approximately 6000 careworkers and 160 administrators.
      Survey questionnaires will include variables on organizational facility
      characteristics and resident outcomes, careworker socio-demographic and
      professional characteristics, the quality of their work environments, resident
      safety climates and careworker outcomes. Appropriate descriptive and comparative
      analysis will be used and multivariate and multilevel analyses will be applied to
      examine the relationships among the various factors including quality of the work
      environment, safety climate, work stressors, rationing of care, workload,
      careworker and resident characteristics, as well as resident and careworker
      outcomes. DISCUSSION: The study results will contribute to a comprehensive
      understanding of the interrelationships between key organizational factors and
      resident/careworker outcomes and will also support planning and conducting
      interventions to improve quality of care concerning organizational factors
      affecting careworkers in daily practice.

PMID- 24102651
TI  - Synergistic interaction and mode of action of Citrus hystrix essential oil
      against bacteria causing periodontal diseases.
AB  - CONTEXT: Citrus hystrix de Candolle (Rutaceae), an edible plant regularly used as
      a food ingredient, possesses antibacterial activity, but there is no current data
      on the activity against bacteria causing periodontal diseases. OBJECTIVE: C.
      hystrix essential oil from leaves and peel were investigated for antibiofilm
      formation and mode of action against bacteria causing periodontal diseases.
      MATERIALS AND METHODS: In vitro antibacterial and antibiofilm formation
      activities were determined by broth microdilution and time kill assay. Mode of
      action of essential oil was observed by SEM and the active component was
      identified by bioautography and GC/MS. RESULTS AND DISCUSSION: C. hystrix leaves
      oil exhibited antibacterial activity at the MICs of 1.06 mg/mL for P. gingivalis
      and S. mutans and 2.12 mg/mL for S. sanguinis. Leaf oil at 4.25 mg/mL showed
      antibiofilm formation activity with 99% inhibition. The lethal effects on P.
      gingivalis were observed within 2 and 4 h after treated with 4 * MIC and 2 * MIC,
      respectively. S. sanguinis and S. mutans were completely killed within 4 and 8 h
      after exposed to 4 * MIC and 2 * MIC of oil. MICs of tested strains showed 4
      times reduction suggesting synergistic interaction of oil and chlorhexidine.
      Bacterial outer membrane was disrupted after treatment with leaves oil.
      Additionally, citronellal was identified as the major active compound of C.
      hystrix oil. CONCLUSIONS: C. hystrix leaf oil could be used as a natural active
      compound or in combination with chlorhexidine in mouthwash preparations to
      prevent the growth of bacteria associated with periodontal diseases and biofilm
      formation.

PMID- 24102653
TI  - Socioeconomic, behavioral, and anthropometric risk factors for traumatic dental
      injuries in childhood: a cohort study.
AB  - AIM: To investigate risk factors for the occurrence of traumatic dental injuries
      (TDI) at 4 years of age. DESIGN: Prospective cohort study. METHODS: A birth
      cohort (n = 500) was recruited from the public healthcare system in Sao Leopoldo,
      Brazil. Demographic, socioeconomic, anthropometric, and behavioral variables were
      collected at 6 months, 1 year, and 4 years of age. Clinical examinations at 4
      years of age were carried out by a single examiner using the Andreasen
      classification. Poisson regression was used to determine risk factors for the
      occurrence of TDI at 4 years of age. RESULTS: A total of 23.7% of the children
      (80/337) exhibited TDI at 4 years of age. The risk of TDI was 35% lower among
      children who had been breastfeed for >=6 months relative risk (RR 0.65; 95% CI
      0.43-0.97) and more than twofold higher among those who were bottle fed >= three
      times a day (RR 2.37; 95% CI 1.10-5.11) at 12 months of age. Higher household
      income in the first year of life and greater height at 4 years of age were
      significantly associated with the outcome. CONCLUSIONS: The identification of
      behavioral, socioeconomic, and anthropometric risk factors for TDI in early
      childhood can contribute to the elaboration of prevention strategies.

PMID- 24102652
TI  - Conservation phylogeography: does historical diversity contribute to regional
      vulnerability in European tree frogs (Hyla arborea)?
AB  - Documenting and preserving the genetic diversity of populations, which conditions
      their long-term survival, have become a major issue in conservation biology. The
      loss of diversity often documented in declining populations is usually assumed to
      result from human disturbances; however, historical biogeographic events,
      otherwise known to strongly impact diversity, are rarely considered in this
      context. We apply a multilocus phylogeographic study to investigate the late
      Quaternary history of a tree frog (Hyla arborea) with declining populations in
      the northern and western part of its distribution range. Mitochondrial and
      nuclear polymorphisms reveal high genetic diversity in the Balkan Peninsula, with
      a spatial structure moulded by the last glaciations. While two of the main
      refugial lineages remained limited to the Balkans (Adriatic coast, southern
      Balkans), a third one expanded to recolonize Northern and Western Europe, loosing
      much of its diversity in the process. Our findings show that mobile and a priori
      homogeneous taxa may also display substructure within glacial refugia ('refugia
      within refugia') and emphasize the importance of the Balkans as a major European
      biodiversity centre. Moreover, the distribution of diversity roughly coincides
      with regional conservation situations, consistent with the idea that historically
      impoverished genetic diversity may interact with anthropogenic disturbances, and
      increase the vulnerability of populations. Phylogeographic models seem important
      to fully appreciate the risks of local declines and inform conservation
      strategies. 

PMID- 24102654
TI  - Benign lymphangioendothelioma: a clinical, histopathologic and
      immunohistochemical analysis of four cases.
AB  - BACKGROUND: Benign lymphangioendothelioma represents a rare lymphatic vascular
      proliferation characterized by proliferation of irregular and thin-walled vessels
      dissecting amongst dermal collagen. Immunohistochemical analysis has been lacking
      in most previously reported cases. METHODS: Herein, we report the clinical and
      histopathologic characteristics of four cases of benign lymphangioendothelioma.
      Immunohistochemical study was completed for all lesions. RESULTS: All lesions
      presented as large, red to brown patches or plaques. Three lesions were located
      on the thigh and one lesion was located on the neck. Histopathologically, all
      lesions showed proliferation of anastomotic or retiform thin-walled vessels with
      a single layer of endothelial cells that dissect the dermis. D2-40 and Prox1
      immunostains were positive and Wilms tumor 1 (WT-1) immunostain was negative in
      all cases. CONCLUSION: Benign lymphangioendothelioma represents a lymphatic
      vascular proliferation. A lack of expression of WT-1 suggests it represents a
      lymphatic vascular malformation.

PMID- 24102655
TI  - Evaluation of internal peer-review to train nurses recruiting to a randomized
      controlled trial--Internal Peer-review for Recruitment Training in Trials
      (InterPReTiT).
AB  - AIM: A discussion and qualitative evaluation of the use of peer-review to train
      nurses and optimize recruitment practice in a randomized controlled trial.
      BACKGROUND: Sound recruitment processes are critical to the success of randomized
      controlled trials. Nurses recruiting to trials must obtain consent for an
      intervention that is administered for reasons other than anticipated benefit to
      the patient. This requires not only patients' acquiescence but also evidence that
      they have weighed the relevant information in reaching their decision. How trial
      information is explained is vital, but communication and training can be
      inadequate. DESIGN: A discussion of a new process to train nurses recruiting to a
      randomized controlled trial. DATA SOURCES: Literature from 1999-2013 about
      consenting to trials is included. Over 3 months from 2009-2010, recruiting nurses
      reviewed recruitment interviews recorded during the pilot phase of a single-site
      randomized controlled trial and noted content, communication style and
      interactions. They discussed their findings during peer-review meetings, which
      were audio-recorded and analysed using qualitative methodology. IMPLICATIONS FOR
      NURSING: Peer-review can enhance nurses' training in trial recruitment procedures
      by supporting development of the necessary communication skills, facilitating
      consistency in information provision and sharing best practice. CONCLUSIONS:
      Nurse-led peer-review can provide a forum to share communication strategies that
      will elicit and address participant concerns and obtain evidence of participant
      understanding prior to consent. Comparing practice can improve consistency and
      accuracy of trial information and facilitate identification of recruitment
      issues. Internal peer-review was well accepted and promoted team cohesion.
      Further evaluation is needed.

PMID- 24102656
TI  - Complete heart block following valve surgery: violation of the "primum non
      nocere" maxim or a minor secondary event?

PMID- 24102657
TI  - The RNA-seq approach to discriminate gene expression profiles in response to
      melatonin on cucumber lateral root formation.
AB  - Cucumber is a model cucurbitaceous plant with a known genome sequence which is
      important for studying molecular mechanisms of root development. In this study,
      RNA sequencing was employed to explore the mechanism of melatonin-induced lateral
      root formation in cucumber under salt stress. Three groups of seeds were
      examined, that is, seeds primed without melatonin (CK), seeds primed in a
      solution containing 10 or 500 MUmol/L melatonin (M10 and M500, respectively).
      These seeds were then germinated in NaCl solution. The RNA-seq analysis generated
      16,866,670 sequence reads aligned with 17,920 genes, which provided abundant data
      for the analysis of lateral root formation. A total of 17,552, 17,450, and 17,393
      genes were identified from roots of the three treatments (CK, M10 and M500,
      respectively). The expression of 121 genes was significantly up-regulated, and
      196 genes were significantly down-regulated in M500 which showed an obvious
      increase on the number of lateral roots. These genes were significantly enriched
      in 57 KEGG pathways and 16 GO terms (M500 versus CK). Based on their expression
      pattern, peroxidase-related genes were selected as the candidates to be involved
      in the melatonin response. Several transcription factor families might play
      important roles in lateral root formation processes. A number of genes related to
      cell wall formation, carbohydrate metabolic processes, oxidation/reduction
      processes, and catalytic activity also showed different expression patterns as a
      result of melatonin treatments. This RNA-sequencing study will enable the
      scientific community to better define the molecular processes that affect lateral
      root formation in response to melatonin treatment.

PMID- 24102658
TI  - Glutamate neurons in the substantia nigra compacta and retrorubral field.
AB  - Dopaminergic neurons of the substantia nigra compacta (SNC), ventral tegmental
      area (VTA) and retrorubral field (RRF) play a role in reward, motivation,
      learning, memory, and movement. These neurons are intermingled with GABAergic
      neurons. Recent evidence shows that the VTA contains glutamatergic neurons
      expressing vesicular glutamate transporter type 2 (VGluT2); some of them co
      express tyrosine hydroxylase (TH). Here, we used a combination of radioactive in
      situ hybridisation and immunohistochemistry to explore whether any of the
      vesicular glutamate transporters [vesicular glutamate transporter type 1
      (VGluT1), VGluT2, or vesicular glutamate transporter type 3 (VGluT3)] were
      encoded by neurons in the SNC or RRF. We found expression of VGluT2 mRNA, but not
      of VGluT1 or VGluT3, in the SNC and RRF. These VGluT2 neurons rarely showed TH
      immunoreactivity. Within the SNC, the VGluT2 neurons were infrequently found at
      the rostral level, but were often seen at the medial and caudal levels
      intercalated in the mediolateral portion of the dorsal tier, at a ratio of one
      VGluT2 neuron per 4.4 TH neurons. At this level, VGluT2 neurons were also found
      in the adjacent substantia nigra reticulata and substantia nigra pars lateralis.
      Within the RRF, the VGluT2 neurons showed an increasing rostrocaudal gradient of
      distribution. The RRF proportion of VGluT2 neurons in relation to TH neurons was
      constant throughout the rostrocaudal levels, showing an average ratio of one
      VGluT2 neuron per 1.7 TH neurons. In summary, we provide evidence indicating that
      the SNC and RRF, which are traditionally considered to be dopaminergic areas,
      have neurons with the ability to participate in glutamate signaling. 

PMID- 24102659
TI  - Informal caregivers' participation when older adults in Norway are discharged
      from the hospital.
AB  - This paper describes the participation of informal caregivers in the discharge
      process when patients aged 80 and over who were admitted from home to different
      hospitals in Norway were discharged to long-term community care. Data for this
      cross-sectional survey were collected through telephone interviews with a
      consecutive sample of 262 caregivers recruited between October 2007 and May 2009.
      The Discharge of Elderly Questionnaire was developed by the research team and was
      designed to elicit data concerning informal caregivers' self-reported perceptions
      on participation in the discharge process. A descriptive and comparative analysis
      of Thompson's levels of participation reported by the older generation (spouses
      and siblings) and the younger generation (adult children and children-in-law,
      nieces and grandchildren) was undertaken using bivariate cross-tabulations and
      chi-square tests for association and trend. Analyses showed that the younger
      generation of caregivers received and provided information to hospital staff to a
      greater degree than the older generation. Overall, 52% of the informal caregivers
      reported co-operating with the staff to a high or to some degree. A multivariate
      logistic regression analysis was used to analyse factors predicting the
      likelihood of informal caregivers reporting co-operation with hospital staff. The
      odds of younger generation caregivers reporting co-operation were more than twice
      as high (OR = 2.121, P = 0.045) as the odds of the older generation. Caregivers
      of patients with a hearing impairment had higher odds of reporting co-operation
      (OR = 1.722, P = 0.049) than caregivers of patients with no such impairment. The
      length of hospital stay, the caregiver's and patient's gender and education level
      were not significantly associated with caregiver's co-operation. The informal
      caregivers' experiences with information practices and user participation in
      hospitals highlight important challenges that must be taken seriously to ensure
      co-operation between families and hospitals when elderly patients are discharged
      back to the community.

PMID- 24102661
TI  - Maize flour fortification in Africa: markets, feasibility, coverage, and costs.
AB  - The economic feasibility of maize flour and maize meal fortification in Kenya,
      Uganda, and Zambia is assessed using information about the maize milling
      industry, households' purchases and consumption levels of maize flour, and the
      incremental cost and estimated price impacts of fortification. Premix costs
      comprise the overwhelming share of incremental fortification costs and vary by
      50% in Kenya and by more than 100% across the three countries. The estimated
      incremental cost of maize flour fortification per metric ton varies from $3.19 in
      Zambia to $4.41 in Uganda. Assuming all incremental costs are passed onto the
      consumer, fortification in Zambia would result in at most a 0.9% increase in the
      price of maize flour, and would increase annual outlays of the average maize
      flour-consuming household by 0.2%. The increases for Kenyans and Ugandans would
      be even less. Although the coverage of maize flour fortification is not likely to
      be as high as some advocates have predicted, fortification is economically
      feasible, and would reduce deficiencies of multiple micronutrients, which are
      significant public health problems in each of these countries. 

PMID- 24102660
TI  - luxS in bacteria isolated from 25- to 40-million-year-old amber.
AB  - Interspecies bacterial communication is mediated by autoinducer-2, whose
      synthesis depends on luxS. Due to the apparent universality of luxS (present in
      more than 40 bacterial species), it may have an ancient origin; however, no
      direct evidence is currently available. We amplified luxS in bacteria isolated
      from 25- to 40-million-year-old amber. The phylogenies and molecular clocks of
      luxS and the 16S rRNA gene from ancient and extant bacteria were determined as
      well. Luminescence assays using Vibrio harveyi BB170 aimed to determine the
      activity of luxS. While the phylogeny of luxS was very similar to that of extant
      Bacillus spp., amber isolates exhibited unique 16S rRNA gene phylogenies. This
      suggests that luxS may have been acquired by horizontal transfer millions of
      years ago. Molecular clocks of luxS suggest slow evolutionary rates, similar to
      those of the 16S rRNA gene and consistent with a conserved gene. Dendograms of
      the 16S rRNA gene and luxS show two separate clusters for the extant and ancient
      bacteria, confirming the uniqueness of the latter group. 

PMID- 24102662
TI  - Secondary syphilis with numerous eosinophils.

PMID- 24102663
TI  - Low prevalence of renal dysfunction in HIV-infected pregnant women: implications
      for guidelines for the prevention of mother-to-child transmission of HIV.
AB  - OBJECTIVE: Emerging international guidelines for the prevention of mother-to
      child transmission of HIV infection across sub-Saharan Africa call for the
      initiation of a triple-drug antiretroviral regimen containing tenofovir, a
      potentially nephrotoxic agent, in all HIV-infected pregnant women at the first
      antenatal clinic visit. While there are significant benefits to the rapid
      initiation of antiretroviral therapy (ART) in pregnancy, there are few data on
      the prevalence of pre-existing renal disease in HIV-infected pregnant women and
      in turn, the potential risks of this approach are not well understood. METHODS:
      We analysed data on renal function in consecutive patients eligible for ART at a
      large primary healthcare clinic in Cape Town. All individuals were screened for
      renal dysfunction via serum creatinine and estimation of creatinine clearance via
      the Cockroft-Gault equation. RESULTS: Over a 2-year period, 238 pregnant women,
      1014 non-pregnant women and 609 men were screened to initiate ART. Pregnant women
      eligible were significantly younger, in earlier stages of HIV disease, had higher
      CD4 cell counts and lower HIV viral loads, than non-pregnant adults. The median
      serum creatinine in pregnant women (46 umol/L) was significantly lower and the
      median creatinine clearance (163 ml/min/1.73 m(2) ) was significantly higher than
      other groups (P < 0.001 and P = 0.004, respectively). Fewer than 1% of pregnant
      women had moderate renal dysfunction before ART initiation, with no instances of
      severe dysfunction observed, compared to 7% moderate or severe renal dysfunction
      in non-pregnant women or men (P < 0.001). CONCLUSION: Renal dysfunction in HIV
      infected pregnant women is significantly less common than in other HIV-infected
      adults eligible for ART. The risks associated with initiating tenofovir
      immediately in pregnant women before reviewing serum creatinine results may be
      limited, and the benefits of rapid ART initiation in pregnancy may outweigh
      possible risks of nephrotoxicity.

PMID- 24102664
TI  - Problems in methods for the detection of significant proteinuria in pregnancy.
AB  - AIM: The aim of this study was to underscore problems associated with the
      dipstick test and determination of protein concentration alone in spot-urine (P
      test) compared with spot-urine protein-to-creatinine ratio (P/Cr test) and to
      determine whether urine collection for 24-h test was complete. MATERIAL AND
      METHODS: Dipstick and P/Cr tests were performed simultaneously in 357 random spot
      urine specimens from 145 pregnant women, including 35 with pre-eclampsia.
      Positive results were defined as >= 1+ on dipstick test, protein concentration >=
      30 mg/dL on P-test, and P/Cr ratio >= 0.27 (mg/mg) on P/Cr test. Sixty-four 24-h
      urine tests (quantification of protein in urine collected during 24 h) were
      performed in 27 of the 145 women. We assumed that P/Cr ratio >= 0.27 predicted
      significant proteinuria (urinary protein >= 0.3 g/day). The 24-h urine collection
      was considered incomplete when urinary creatinine excretion was <11.0 mg/kg/day
      or >25.0 mg/kg/day. RESULTS: Forty-four percent (69/156) of specimens with a
      positive test result on dipstick test contained protein < 30 mg/dL. Dipstick test
      was positive for 25.7% (69/269) of specimens with protein < 30 mg/dL and for
      28.8% (79/274) of specimens with P/Cr ratio < 0.27. P-test results were positive
      for 7.3% (20/274) and negative for 18.1% (15/83) of specimens with P/Cr ratio <
      0.27 and >= 0.27, respectively. Incomplete 24-h urine collection occurred in
      15.6% (10/64) of 24-h urine tests. Daily urinary creatinine excretion was 702
      1397 mg, while creatinine concentration varied from 16 mg/dL to 475 mg/dL in spot
      urine specimens. CONCLUSION: Dipstick test and P-test were likely to over- and
      underestimate risks of significant proteinuria, respectively. The 24-h urine
      collection was often incomplete.

PMID- 24102665
TI  - Accuracy of low-field magnetic resonance imaging versus radiography for guiding
      injection of equine distal interphalangeal joint collateral ligaments.
AB  - Desmopathy of the distal interphalangeal joint collateral ligament is a common
      cause of lameness in the horse and carries a variable prognosis for soundness.
      Intralesional treatment has been proposed for improving outcome; however, limited
      reports describe methods for injecting this ligament. The purpose of this study
      was to compare accuracy of low-field magnetic resonance imaging (MRI) vs.
      radiography for injecting the collateral ligament of the distal interphalangeal
      joint. Equine cadaver digit pairs (n = 10) were divided by random assignment to
      injection of the ligament by either technique. An observer unaware of injection
      technique determined injection success based on postinjection MRI and/or gross
      sections acquired from the proximal, middle, and distal portions of the ligament.
      McNemar's test was performed to determine statistical difference between
      injection techniques, the number of injection attempts, and injection of the
      medial or lateral collateral ligament. Magnetic resonance imaging guided
      injection was successful more frequently than radiographic-guided injection based
      on postinjection MRI (24 of 30 vs. 9 of 30; P = 0.0006) and gross sections (26 of
      30 vs. 13 of 30; P = 0.0008). At each level of the ligament (proximal, middle,
      and distal), MRI-guided injection resulted in more successful injections than
      radiographic guidance. Statistical significance occurred at the proximal aspect
      of the collateral ligament based on postinjection MRI (P = 0.0143) and the middle
      portion of the ligament based on gross sections (P = 0.0253). Findings supported
      future testing of standing, low-field MRI as a technique for delivering
      intralesional regenerative therapy in live horses with desmopathy of these
      collateral ligaments. 

PMID- 24102666
TI  - Postoperative emergence delirium in pediatric patients undergoing cataract
      surgery--a comparison of desflurane and sevoflurane.
AB  - BACKGROUND: Desflurane and sevoflurane are associated with postoperative
      emergence delirium (ED) in children. The study aimed to compare the use of
      desflurane and sevoflurane to determine the postoperative ED in children
      undergoing cataract surgery using the validated Pediatric Anesthesia Emergence
      Delirium (PAED) scale. METHODS: In this randomized double-blinded study, 88
      children of American Society of Anesthesiologists (ASA) grade I and II aged 2-6
      years, anesthesia was maintained with 1-1.2 MAC concentration of desflurane or
      sevoflurane after induction with sevoflurane. Subtenon block was administered in
      all children with 0.08-0.10 ml.kg(-1) of 0.5% bupivacaine before surgical
      incision. Primary outcome measured was PAED scale at different time intervals
      between the two groups, and secondary outcome measured was preoperative anxiety
      scores, postoperative pain scores, emergence, incidence of delirium and adverse
      effects. RESULTS: Pediatric Anesthesia Emergence Delirium (PAED) scale showed no
      statistical difference between sevoflurane and desflurane at different time
      intervals. Incidence of ED using the cutoff of >12 in PAED scale was 8 of 44
      (18.18%) in sevoflurane group and 9 of 44 (20.45%) in desflurane groups (P =
      1.000). Emergence from anesthesia was faster in desflurane group (P = 0.001).
      Correlation between the m-YPAS anxiety scale and PAED scale in either group did
      not find any relationship (correlation coefficient = -0.060, P = 0.579). No
      correlation between the Face, Legs, Activity, Cry and Consolability (FLACC) scale
      and Pediatric Anesthesia Emergence Delirium (PAED) scale was found in 17 patients
      who had ED (correlation coefficient = 0.191, P-value = 0.462). Five patients of
      17 (i.e., three patients in Group S and two patients in Group D) had PAED >12 but
      FLACC <4. CONCLUSION: Emergence delirium (ED) after desflurane and sevoflurane
      anesthesia was comparable using a validated PAED scale in pediatric cataract
      surgery. There was no correlation between preoperative anxiety and ED in these
      children; however, children with higher pain scores were more likely to have a
      higher ED.

PMID- 24102667
TI  - Intracranial metastasis from a "giant" nonoperated sacrococcygeal chordoma: an
      underestimated metastatic potential?

PMID- 24102668
TI  - Left ventricular rotation and torsion in patients with perimembranous ventricular
      septal defect.
AB  - BACKGROUND: Assessment of left ventricular (LV) rotation has become an important
      approach for quantifying LV function. In this study, we sought to analyze LV
      rotation and twist using speckle tracking imaging (STI) in adult patients with
      isolated ventricular septal defects. METHODS: Using STI, the peak rotation and
      time to peak rotation of 6 segments in basal and apical short-axis were measured,
      respectively, in 32 patients with ventricular septal defect and 30 healthy
      subjects as controls. The global rotation of the 6 segments in basal and apical
      and LV twist versus time profile were drawn, the peak rotation and twist of LV
      were calculated. All the time to peak rotation/twist were expressed as a
      percentage of end-systole (end-systole = 100%). Left ventricular ejection
      fraction was measured by biplane Simpson method. RESULTS: In patients group, the
      peak rotation of posterior, inferior, and postsept wall in basal was higher(P <=
      0.05) and LV twist was also higher (P <= 0.05) than healthy controls. There were
      no significant differences between 2 groups in the peak rotation of the other 9
      segments and left ventricular ejection fraction. Different from the control
      group, the time to peak rotation of the 6 segments in basal were delayed and the
      global rotation of the base was delayed (P <= 0.05) in ventricular septal defect
      group. CONCLUSIONS: Left ventricular volume overload due to ventricular septal
      defect has significant effect on LV rotation and twist, and LV rotation and twist
      may be a new index predicting LV systolic function.

PMID- 24102669
TI  - Stimulating effects of quercetin and phenamil on differentiation of human dental
      pulp cells.
AB  - Dentin formation is preferred in the healing response of the pulp to pulp-capping
      agents during vital pulp therapy. Enhancement of the dentinogenic differentiation
      of dental pulp cells is thought to accelerate pulp repair. The aim of this study
      was to evaluate the dentinogenic activity of small molecules (three flavonoids
      and phenamil) that have been shown previously to induce osteoblast
      differentiation. Among the flavonoids (quercetin, genistein and baicalin),
      quercetin induced the highest alkaline phosphatase (ALP) activity of human dental
      pulp (HDP) cells. Phenamil, an amiloride derivative, elicited higher ALP activity
      than quercetin. However, increased expression of dentin sialophosphoprotein
      (DSPP) mRNA and mineral deposition were seen in cultures treated with quercetin
      compared with phenamil. This would seem to suggest that quercetin is the most
      dentinogenic agent among the tested chemicals. The increase in ALP activity in
      the quercetin-treated cells was not affected by ICI 182,780, an estrogen receptor
      inhibitor, and was partially blocked by PD98059, an extracellular signal
      regulated kinase 1/2 (ERK1/2) inhibitor. This suggests that ERK1/2 is activated
      in the quercetin-induced differentiation of HDP cells without the mediation of
      estrogen receptors, which are known to be involved in osteoblast differentiation
      induced by quercetin. 

PMID- 24102670
TI  - A molecular diagnostic tool for the preliminary assessment of host-parasitoid
      associations in biological control programmes for a new invasive pest.
AB  - Evaluation of host-parasitoid associations can be tenuous using conventional
      methods. Molecular techniques are well placed to identify trophic links and
      resolve host-parasitoid associations. Establishment of the highly invasive brown
      marmorated stink bug, Halyomorpha halys (Hemiptera: Pentatomidae), outside Asia
      has prompted interest in the use of egg parasitoids (Hymenoptera: Scelionidae) as
      biological control agents. However, little is known regarding their host ranges.
      To address this, a DNA barcoding approach was taken wherein general PCR primers
      for Scelionidae and Pentatomidae were developed to amplify and sequence >500-bp
      products within the DNA barcoding region of the cytochrome oxidase I (COI) gene
      that would permit the identification of key players in this association.
      Amplification of DNA from Pentatomidae and Scelionidae was consistent across a
      broad range of taxa within these families, and permitted the detection of
      Scelionidae eggs within H. halys 1 h following oviposition. In laboratory assays,
      amplification and sequencing of DNA from empty, parasitized eggs was successful
      for both host (100% success) and parasitoid (50% success). When applied to field
      collected, empty egg masses, the primers permitted host identification in 50-100%
      of the eggs analysed, and yielded species-level identifications. Parasitoid
      identification success ranged from 33 to 67% among field-collected eggs, with
      genus-level identification for most specimens. The inability to obtain species
      level identities for these individuals is due to the lack of coverage of this
      taxonomic group in public DNA sequence databases; this situation is likely to
      improve as more species are sequenced and recorded in these databases. These
      primers were able to detect and identify both pentatomid host and scelionid
      parasitoid in a hyperparasitized egg mass, thereby clarifying trophic links
      otherwise unresolved by conventional methodology.

PMID- 24102671
TI  - Structural responses to the obesity and non-communicable diseases epidemic: the
      Chilean Law of Food Labeling and Advertising.
AB  - In 12 July 2012, the Chilean Senate approved the Law of Food Labeling and
      Advertising, resulting from the joint efforts of a group of health professionals,
      researchers and legislators who proposed a regulatory framework in support of
      healthy diets and active living. Its goal was to curb the ongoing epidemic
      increase of obesity and non-communicable diseases. Two actions included: (i)
      improving point of food purchase consumer information by incorporating easy-to
      understand front-of-packages labeling and specific messages addressing critical
      nutrients, and (ii) decreasing children's exposure to unhealthy foods by
      restricting marketing, advertising and sales. We summarize the work related to
      the law's release and discuss the conclusions reached by the various expert
      committees that were convened by the Ministry of Health to guide the development
      of the regulatory norms. Throughout the process, the food industry has overtly
      expressed its disagreement with the regulatory effort. The final content of the
      regulatory norms is still pending; however there are suggestions that its
      implementation will be delayed and might be modified based on the industry
      lobbying actions. These lessons should contribute to show the need of
      anticipating and addressing potential barriers to obesity-prevention policy
      implementation, particularly with respect to the role of the private sector. 

PMID- 24102672
TI  - Pharmacokinetics, biodistribution and bioavailability of isoliquiritigenin after
      intravenous and oral administration.
AB  - CONTEXT: Isoliquiritigenin (ISL) has been shown to exhibit a variety of
      biological activities. However, there is little research on the pharmacokinetic
      behavior and tissues distribution of ISL. OBJECTIVE: Pharmacokinetics,
      biodistribution and bioavailability of ISL after intravenous and oral
      administration were determined by systematic investigation in Sprague-Dawley
      rats. MATERIALS AND METHODS: ISL was dissolved in medicinal ethanol-Tween 80-0.9%
      sodium chloride saline in a volume ratio of 10:15:75. The ISL solution was
      injected in rats via a tail vein at a single dose of 10, 20 and 50 mg/kg and
      administered orally in rats at a single dose of 20, 50 and 100 mg/kg,
      respectively. Blood samples were collected at time intervals of 0.08, 0.25, 0.5,
      0.75, 1, 1.5, 2, 3, 6, 8 and 12 h after intravenous injection. Tissues of
      interests in mice were collected immediately at each determined time point (0.5,
      1, 2, 3 and 6 h) after cervical dislocation. RESULTS: The dose-normalized AUC
      values were 7.3, 7.6 and 8.7 MUg * h/ml (calculated based on the dose of 10
      mg/kg) for intravenous doses of 10, 20 and 50 mg/kg, respectively. The
      elimination half-lifes (t1/2lambda) were 4.9, 4.6 and 4.8 h at 10, 20 and 50
      mg/kg intravenous doses, respectively. The F values were 29.86, 22.70, 33.62% for
      oral doses of 20, 50 and 100 mg/kg, respectively. Liver, heart and kidney were
      major distribution tissues of ISL in mice. The plasma protein binding of ISL in
      rats was 43.72%. CONCLUSION: The work may useful for further study of the
      bioactive mechanism of ISL.

PMID- 24102673
TI  - Plum pox virus and sharka: a model potyvirus and a major disease.
AB  - TAXONOMIC RELATIONSHIPS: Plum pox virus (PPV) is a member of the genus Potyvirus
      in the family Potyviridae. PPV diversity is structured into at least eight
      monophyletic strains. GEOGRAPHICAL DISTRIBUTION: First discovered in Bulgaria,
      PPV is nowadays present in most of continental Europe (with an endemic status in
      many central and southern European countries) and has progressively spread to
      many countries on other continents. GENOMIC STRUCTURE: Typical of potyviruses,
      the PPV genome is a positive-sense single-stranded RNA (ssRNA), with a protein
      linked to its 5' end and a 3'-terminal poly A tail. It is encapsidated by a
      single type of capsid protein (CP) in flexuous rod particles and is translated
      into a large polyprotein which is proteolytically processed in at least 10 final
      products: P1, HCPro, P3, 6K1, CI, 6K2, VPg, NIapro, NIb and CP. In addition, P3N
      PIPO is predicted to be produced by a translational frameshift. PATHOGENICITY
      FEATURES: PPV causes sharka, the most damaging viral disease of stone fruit
      trees. It also infects wild and ornamental Prunus trees and has a large
      experimental host range in herbaceous species. PPV spreads over long distances by
      uncontrolled movement of plant material, and many species of aphid transmit the
      virus locally in a nonpersistent manner. SOURCES OF RESISTANCE: A few natural
      sources of resistance to PPV have been found so far in Prunus species, which are
      being used in classical breeding programmes. Different genetic engineering
      approaches are being used to generate resistance to PPV, and a transgenic plum,
      'HoneySweet', transformed with the viral CP gene, has demonstrated high
      resistance to PPV in field tests in several countries and has obtained regulatory
      approval in the USA.

PMID- 24102674
TI  - Histopathology of the red lunula: new histologic features and clinical
      correlations of a rare type of erythronychia.
AB  - The lunula is the semi-lunar shaped area seen at the proximal aspect of the nail
      unit. It is the most distal aspect of the nail matrix that can be visualized
      through the transparent nail plate. The term red lunula describes erythema that
      partially or completely replaces the normal white color of the lunula. Red
      lunulae have been associated with a number of dermatologic and systemic
      conditions. However, the etiology and histopathology of the red lunula have not
      been characterized. We report a case of red lunulae of the fingernails in an
      adult male. Histopathologic examination revealed an increased density of benign
      appearing and mildly dilated vascular channels present in the superficial
      papillary dermis of the nail matrix. To our knowledge, this is the first report
      of distinct pathologic findings seen on histologic examination of a red lunula.
      The increased vascularity of the lunula seen microscopically correlates with the
      clinically observed red color. These findings raise the possibility that systemic
      or local factors are responsible for angiogenesis within the nail unit in
      disorders associated with the red lunula. 

PMID- 24102676
TI  - Antibodies to Toxoplasma gondii in individuals with mania.
AB  - OBJECTIVES: Increased rates of infection with Toxoplasma gondii have been found
      in individuals with schizophrenia as compared to control groups but this issue
      has not been studied in mania. METHODS: We measured immunoglobulin G (IgG) and
      IgM class antibodies to T. gondii in 57 individuals with mania who were assessed
      at up to three time-points. We also measured these antibodies in 743 individuals
      in other psychiatric groups and in 314 non-psychiatric controls. T. gondii
      antibody levels were compared among groups by multivariate analyses. IgG class
      and IgM class antibodies to cytomegalovirus were also measured in the same
      samples. T. gondii antibody levels were also compared over time in the mania
      group. RESULTS: The mania group had a significantly elevated level of IgM
      antibodies to T. gondii as compared to the control individuals without a
      psychiatric diagnosis [odds ratio (OR) = 2.33, p < 0.04 at hospital admission;
      and OR = 2.32, p < 0.02 at study entry during the hospital stay]. Elevated IgM
      class antibodies to T. gondii were not found in individuals with the other
      psychiatric diagnoses. We also did not find an increased level of IgG class
      antibodies to T. gondii or IgG or IgM class antibodies to CMV in the individuals
      with mania. Within the mania group, there was a significant difference between
      the prevalences of increased levels of T. gondii IgM at the baseline and the
      follow-up time-point (t = 2.97, p < 0.003). CONCLUSIONS: Infection with T. gondii
      may confer risk for mania.

PMID- 24102675
TI  - Intracerebral hemorrhage and delirium symptoms. Length of stay, function, and
      quality of life in a 114-patient cohort.
AB  - RATIONALE: The prognostic significance of delirium symptoms in intensive care
      unit (ICU) patients with focal neurologic injury is unclear. OBJECTIVES: To
      determine the relationship between delirium symptoms and subsequent functional
      outcomes and quality of life (QOL) after intracerebral hemorrhage. METHODS: We
      prospectively enrolled 114 patients. Delirium symptoms were routinely assessed
      twice daily using the Confusion Assessment Method for the ICU by trained nurses.
      Functional outcomes were recorded with modified Rankin Scale (scored from 0 [no
      symptoms] to 6 [dead]), and QOL outcomes with Neuro-QOL at 28 days, 3 months, and
      12 months. MEASUREMENTS AND MAIN RESULTS: Thirty-one (27%) patients had delirium
      symptoms ("ever delirious"), 67 (59%) were never delirious, and the remainder
      (14%) had persistent coma. Delirium symptoms were nearly always hypoactive, were
      detected mean 6 days after intracerebral hemorrhage presentation, and were
      associated with longer ICU length of stay (mean 3.5 d longer in ever vs. never
      delirious patients; 95% confidence interval, 1.5-8.3; P = 0.004) after correction
      for age, admit National Institutes of Health (NIH) Stroke Scale, and any
      benzodiazepine exposure. Delirium symptoms were associated with increased odds of
      poor outcome at 28 days (odds ratio, 8.7; 95% confidence interval, 1.4-52.5; P =
      0.018) after correction for admission NIH Stroke Scale and age, and with worse
      QOL in the domains of applied cognition-executive function and fatigue after
      correcting for the NIH Stroke Scale, age, benzodiazepine exposure, and time of
      follow-up. CONCLUSIONS: After focal neurologic injury, delirium symptoms were
      common despite low rates of infection and sedation exposure, and were predictive
      of subsequent worse functional outcomes and lower QOL.

PMID- 24102677
TI  - Total synthesis of hygrolines and pseudohygrolines.
AB  - A concise two-step synthesis of all four diastereoisomeric hygrolines ((-)
      hygroline (1), (+)-hygroline (2), (-)-pseudohygroline (3), (+)-pseudohygroline
      (4)) has been developed based on the (-)-sparteine (5)- or (+)-sparteine
      surrogate 11-mediated enantioselective lithiation of N-Boc pyrrolidine (6),
      followed by reaction of the chiral anion with (S)- or (R)-propylene oxide.
      Reduction of the resulting N-Boc amino alcohols furnished hygrolines and
      pseudohygrolines in 30% to 56% overall yields with dr's > 95:5. 

PMID- 24102678
TI  - Endocavitary structures in the outflow tract: anatomy and electrophysiology of
      the conus papillary muscles.
AB  - Catheter ablation is an increasingly used and successful treatment choice for
      right ventricular outflow tract (RVOT) arrhythmias. While the role of
      endocavitary structures and the regional morphology of the ventricular inflow
      tract and the right atrium as a cause for difficulty with successful ablation are
      well described, similar issues within the RVOT are not well understood. It is
      also not commonly appreciated that one of the papillary muscles is located within
      the proximal RVOT. We report 3 patients in which ventricular arrhythmia was
      targeted and ablated in the conus papillary muscle. The anatomic features,
      potential role of the fascicular conduction system, and unique challenges with
      mapping arrhythmia arising from this structure are discussed. 

PMID- 24102679
TI  - Synaptic vesicle protein 2A: basic facts and role in synaptic function.
AB  - In recent years, there has been considerable interest in determining the function
      of synaptic vesicle protein 2A and its role as a target for antiepileptic drugs.
      Although it is known that synaptic vesicle protein 2A is involved in normal
      synaptic vesicle function, its participation in synaptic vesicle cycling and
      neurotransmitter release in normal and pathological conditions is unclear.
      However, the experimental evidence suggests that synaptic vesicle protein 2A
      could be a vesicular transporter, regulate synaptic exocytosis as a gel matrix,
      or modulate synaptotagmin-1 activity. This review describes and discusses the
      participation of synaptic vesicle protein 2A in synaptic modulation in normal and
      pathological conditions. 

PMID- 24102680
TI  - Phytol, a diterpene alcohol, inhibits the inflammatory response by reducing
      cytokine production and oxidative stress.
AB  - Studies have shown that diterpenes have anti-inflammatory and redox-protective
      pharmacological activities. The present study aimed to investigate the anti
      inflammatory properties of phytol, a diterpene alcohol, in a mouse model of acute
      inflammation, and phytol effect on leukocyte recruitment, cytokines levels, and
      oxidative stress. The anti-inflammatory activities of phytol were assessed by
      measuring paw edema induced by different inflammatory agents (e.g., lambda
      carrageenan, compound 48/80, histamine, serotonin, bradykinin, and prostaglandin
      E2 [PGE2 ]), myeloperoxidase (MPO) activity, peritonitis model and cytokine
      levels. Further, oxidative stress was evaluated by determining glutathione (GSH)
      levels and malondialdehyde (MDA) concentration. The results showed that phytol
      (7.5, 25, 50, and 75 mg/kg) significantly reduced carrageenan-induced paw edema,
      in a dose-dependent manner. In addition, phytol (75 mg/kg) inhibited compound
      48/80-, histamine-, serotonin-, bradykinin- and PGE2 -induced paw edema. It also
      inhibited the recruitment of total leukocytes and neutrophils; decreased MPO
      activity, tumor necrosis factor-alpha (TNF-alpha) and interleukin-1beta (IL
      1beta) levels, and MDA concentration; and increased GSH levels during carrageenan
      induced acute inflammation. These results suggest that phytol attenuates the
      inflammatory response by inhibiting neutrophil migration that is partly caused by
      reduction in IL-1beta and TNF-alpha levels and oxidative stress. 

PMID- 24102681
TI  - Using the Diffusion of Innovations theory to understand the uptake of genetics in
      nursing practice: identifying the characteristics of genetic nurse adopters.
AB  - AIM: To identify the characteristics of nurses who are using genetics in practice
      and consider the implications of the findings for optimizing its wider uptake.
      BACKGROUND: Nurses are crucial in realizing the benefits from advances in genetic
      and genomic health care. Although many recognize genetics as an important
      component of disease, most feel unprepared to engage with it in practice. The
      Diffusion of Innovation theory provides a useful framework to describe different
      levels of engagement. Identifying the characteristics of nurses who have engaged
      with genetics (adopters) may provide insights of relevance to promoting wider
      adoption. DESIGN: A primarily quantitative approach over two phases, using online
      surveys conducted during 2011. METHOD: In phase 1, consensus (>75%) was sought
      from experts in genetics and nursing on four potential Indicators of Genetic
      Adoption could identify nurses who have adopted genetics. In phase 2, oncology
      and primary care nurses were surveyed to identify the characteristics and
      demographic indicators of genetic nurse adopters. RESULTS: A consensus was
      achieved to include all Indicators of Genetic Adoption (phase 1). In phase 2,
      27.3% of respondents (n = 24/88) were categorized as being adopters. Eighteen
      characteristics were determined to be statistically significant (Mann-Whitney) in
      defining an adopter and included being open to experience and being more
      knowledgeable of and confident in using genetics. CONCLUSION: Nurses can be
      categorized in terms of their engagement with genetics through several
      distinguishing characteristics. Further research is needed to test the
      generalizability of the findings to a larger sample and other areas of nursing
      practice.

PMID- 24102682
TI  - Adolescents let sufficient evidence accumulate before making a decision when
      large incentives are at stake.
AB  - Adolescent decision-making has been described as impulsive and suboptimal in the
      presence of incentives. In this study we examined the neural substrates of
      adolescent decision-making using a perceptual discrimination task for which small
      and large rewards were associated with correctly detecting the direction of
      motion of a cloud of moving dots. Adults showed a reward bias of faster reaction
      times on trials for which the direction of motion was associated with a large
      reward. Adolescents, in contrast, were slower to make decisions on trials
      associated with large rewards. This behavioral pattern in adolescents was
      paralleled by greater recruitment of fronto-parietal regions important in
      representing the accumulation of evidence sufficient for selecting one choice
      over its alternative and the certainty of that choice. The findings suggest that
      when large incentives are dependent on performance, adolescents may require more
      evidence to accumulate prior to responding, to be certain to maximize their
      gains. Adults, in contrast, appear to be quicker in evaluating the evidence for a
      decision when primed by rewards. Overall these findings suggest that rather than
      reacting hastily, adolescents can be incentivized to take more time to make
      decisions when large rewards are at stake. A video abstract of this article can
      be viewed at http://youtu.be/1g4F5vzFDl0. 

PMID- 24102683
TI  - Effects of sevoflurane on the expression of tau protein mRNA and Ser396/404 site
      in the hippocampus of developing rat brain.
AB  - BACKGROUND: General anesthesia induces a transient hyperphosphorylation of tau
      protein that is associated with neurotoxicity in neonatal rats, but the mechanism
      remains unknown. The current study sought to investigate the effects of
      sevoflurane on the levels of tau phosphorylation at phosphor-Ser396/404 and total
      tau mRNA in the hippocampus of neonatal rats. MATERIALS AND METHODS: Thirty-six 7
      day-old rats were randomly exposed for 6 h to either 3% sevoflurane (S) or air
      (NC) as a placebo. They were sacrificed at 1, 7 and 14 days after the anesthesia,
      respectively, and thus assigned to S1d , S7d , S14d , NC1d , NC7d , and NC14d
      groups (n = 6). Their brain tissues were harvested and then subjected to
      histopathologic, Western blot and real-time polymerase chain reaction analysis.
      RESULTS: Microtubule cytoskeletons were arranged in neat parallel rows in rats
      exposed only to air, whereas the microtubules were arranged in a disorderly and
      intermittent (nonparallel) fashion in rats exposed to sevoflurane. The levels of
      tau mRNA in the S1d and S7d groups were significantly higher than those in the
      NC1d and NC7d groups. There was no significant difference in the levels of tau
      mRNA between the S14d and NC14d groups. The levels of tau protein at Ser404 in
      the S1d , S7d, and S14d groups were significantly higher than those in NC1d ,
      NC7d, and NC14d groups. The levels of tau protein at Ser396 in the S1d , and S7d
      groups were significantly higher than those in the NC1d , and NC7d groups, while
      there was no significant difference in the levels of tau protein at Ser396
      between the S14d group and the NC14d group, respectively. CONCLUSION: In rat
      hippocampus, sevoflurane was associated with microtubular disarray as well as
      increased levels of tau mRNA and excessive phosphorylation of tau protein at
      Ser396 and Ser404. This implicates that sevoflurane may induce neurotoxicity.

PMID- 24102684
TI  - Mycobacterial chaperonins: the tail wags the dog.
AB  - Molecular chaperones are defined as proteins that assist the noncovalent assembly
      of other protein-containing structures in vivo, but which are not components of
      these structures when they are carrying out their normal biological functions.
      There are numerous families of protein that fit this definition of molecular
      chaperones, the most ubiquitous of which are the chaperonins and the Hsp70
      families, both of which are required for the correct folding of nascent
      polypeptide chains and thus essential genes for cell viability. The groE genes of
      Escherichia coli were the first chaperonin genes to be discovered, within an
      operon comprising two genes, groEL and groES, that function together in the
      correct folding of nascent polypeptide chains. The identification of multiple
      groEL genes in mycobacteria, only one of which is operon-encoded with a groES
      gene, has led to debate about the functions of their encoded proteins, especially
      as the essential copies are surprisingly often not the operon-encoded genes.
      Comparisons of these protein sequences reveals a consistent functional homology
      and identifies an actinomycete-specific chaperonin family, which may chaperone
      the folding of enzymes involved in mycolic acid synthesis and thus provide a
      unique target for the development of a new class of broad-spectrum
      antimycobacterial drugs. 

PMID- 24102685
TI  - Development of a standardized procedure for testing the efficacy of workplace
      cleansers.
AB  - BACKGROUND: Occupational skin cleansing is a risk factor for cumulative irritant
      dermatitis. Standardized methods are required to assess the cleaning efficacy of
      occupational skin cleansers, allowing us to choose the optimal cleanser with
      minimal irritation for specific workplaces. OBJECTIVES: To develop a standardized
      procedure for testing the cleaning efficacy of occupational skin cleansers.
      METHODS: In this single-blind, randomized, monocentric clinical trial in 24
      healthy volunteers, the cleaning efficacy of generic reference cleansers was
      assessed against standardized test dirts. The test procedure included
      standardized dirt application, standardized washing with an automated skin
      cleaning device, and quantification of the cleaning efficacy by chromametry. For
      two cleansers, reproducibility of the cleaning efficacy assessment was studied.
      Furthermore, the performance of two cleansers was compared with that of
      commercial skin cleansers. RESULTS: Cleaning factors ranged from 12% up to 97%
      for the respective model dirts. A high reproducibility of the washing and the
      assessment procedure could be shown. The comparison of the washing efficacies for
      two reference cleansers with those of commercial cleansers showed partly similar
      performances, but also a higher cleaning efficacy for some dirts of the reference
      cleansers. CONCLUSIONS: The testing procedure proved to be applicable to a wide
      spectrum of cleansers and model dirts.

PMID- 24102686
TI  - Nutrition transition in Bangladesh: is the country ready for this double burden.
AB  - Malnutrition has dominated Bangladesh development, encouraged by the Bangladesh
      Integrated Nutrition Programme under the first Sector-Wide Approach (SWAp) World
      Health Organization, and the United Nations Food and Agriculture Organization. To
      date, all the SWAps for health, nutrition and population well-being have
      identified malnutrition as a priority. Donors, United Nations organizations and
      non-governmental organizations provide extensive support to prevent and tackle
      malnutrition in the country. The government has delineated an effective policy
      response to the high prevalence of undernutrition. Bangladesh has a wide range of
      policies encouraging appropriate infant and young child feeding practices, 6
      months of paid maternity leave in the public sector, school meals for vulnerable
      communities, micronutrient supplementation interventions and more. However,
      almost all of these efforts address the undernutrition aspect of malnutrition,
      neglecting the other form of malnutrition - overnutrition. Trend data from
      national surveys show steady increases in overweight and steady decreases in
      underweight among women of reproductive age. This paper sheds light on the trend
      data, showing the transition from under- to overnutrition and the double burden
      of malnutrition among Bangladeshi women of reproductive age. It also discusses
      the national policy and programme responses to overweight and obesity in
      Bangladesh among the same population. 

PMID- 24102687
TI  - Elevated right ventricular end-diastolic pressure by Doppler echocardiography-a
      case report.
AB  - Careful analysis of the right-sided Doppler signals provides important data
      regarding right heart hemodynamics. Here, we illustrate the value of the combined
      analysis of flow across the hepatic vein, tricuspid valve, and pulmonary valve
      for the diagnosis of elevated right ventricular end-diastolic pressure. 

PMID- 24102688
TI  - Extrafacial indolent CD8-positive cutaneous lymphoid proliferation with unusual
      symmetrical presentation involving both feet.
AB  - Indolent CD8+ cutaneous lymphoid proliferation represents a recently described
      entity among cutaneous T-cell lymphomas that typically presents with solitary
      skin lesions on the face or at acral sites and usually follows an indolent
      clinical course. Histopathologically, this entity is characterized by a dense
      dermal infiltrate of non-epidermotropic, small- to medium-sized pleomorphic CD8+
      T-cells of the non-activated cytotoxic phenotype showing a clear-cut grenz zone
      and a low proliferation index. Distinction from otherwise aggressive T-cell
      lymphomas bearing a cytotoxic CD8+ phenotype is fundamental. We herein present an
      unusual case of indolent CD8+ cutaneous lymphoid proliferation presenting in
      bilateral symmetrical distribution on both feet and lacking the otherwise
      described grenz zone. Our case widens the spectrum of possible clinical and
      histomorphological variations of this entity. Taking into account the distinctive
      and unique clinical and microscopic features of all hitherto published cases of
      indolent CD8+ cutaneous lymphoid proliferation we suppose that this lymphoma
      subtype has to be included as a new and distinct entity in the World Health
      Organisation (WHO)-/European Organisation for Research and Treatment of Cancer
      (EORTC)-classification of cutaneous lymphomas. 

PMID- 24102689
TI  - Bayesian phylogeographic inferences reveal contrasting colonization dynamics
      among European groundwater isopods.
AB  - The potentially important role of northern microrefugia during postglacial
      dispersal is challenging the view of southern Europe as a refuge and source area
      of European biota. In groundwaters, large geographic ranges of presumably good
      dispersers are increasingly suspected to consist of assemblages of cryptic
      species with narrow ranges. Moreover, a large species range, even when confirmed
      by molecular evidence, tells us little about the spatiotemporal dynamics of
      dispersal. Here, we used phylogenetic inferences, species delineation methods and
      Bayesian phylogeographic diffusion models to test for the likelihood of
      postglacial colonization from distant refugia among five morphospecies of
      Proasellus (Isopoda, Asellidae). All morphospecies except one were monophyletic,
      but they comprised a total of 15-17 cryptic species. Three cryptic species
      retained ranges that spanned a distance >650 km, similar to that of the nominal
      morphospecies. Bayesian diffusion models based on mitochondrial markers revealed
      considerable spatiotemporal heterogeneity in dispersal rates, suggesting that
      short-time dispersal windows were instrumental in shaping species ranges. Only
      one species was found to experience a recent, presumably postglacial, range
      expansion. The Jura and Alpine foothills probably played a major role in
      maintaining diversity within Proasellus in northern regions by acting both as
      diversification hotspots and Pleistocene refugia. Gaining insight into the
      spatiotemporal heterogeneity of dispersal rates revealed contrasting colonization
      dynamics among species that were not consistent with a global postglacial
      colonization of Europe from distant refugia. 

PMID- 24102691
TI  - Mandibular trabecular bone as fracture indicator in 80-year-old men and women.
AB  - The objective of the present study was to compare assessments of the mandibular
      bone as fracture risk indicators for 277 men and women. The mandibular trabecular
      bone was evaluated in periapical radiographs, using a visual index, as dense,
      mixed dense and sparse, or sparse. Bone texture was analysed using a computer
      based method in which the number of transitions from trabeculae to
      intertrabecular spaces was calculated. The sum of the sizes and intensities of
      the spaces between the trabeculae was calculated using Jaw-X software. Women had
      a statistically significantly greater number of fractures and a higher frequency
      of sparse mandibular bone. The OR for having suffered a fracture with visually
      sparse trabecular bone was highest for the male group (OR = 5.55) and lowest for
      the female group (OR = 3.35). For bone texture as an indicator of previous
      fracture, the OR was significant for the female group (OR = 2.61) but not for the
      male group, whereas the Jaw-X calculations did not differentiate between
      fractured and non-fractured groups. In conclusion, all bone-quality assessments
      showed that women had a higher incidence of sparse trabecular bone than did men.
      Only the methods of visual assessment and trabecular texture were significantly
      correlated with previous bone fractures.

PMID- 24102692
TI  - Counselling and self-management therapies for temporomandibular disorders: a
      systematic review.
AB  - The aim of this review was to investigate the effectiveness of counselling and
      other self-management-based therapies on muscle and temporomandibular joint (TMJ)
      pain relief and increasing the functional abilities of patients with
      temporomandibular disorders (TMD). A systematic literature review was conducted
      by three independent reviewers and included articles published up to 2012. PubMed
      and Cochrane Library electronic databases were used in addition to hand-searching
      to assess clinical outcomes for counselling and self-management approaches for
      TMD treatment. The review yielded 581 records that were narrowed down to 7. All
      included studies were classified as blind-randomized controlled clinical trials.
      The selected articles analysed revealed that counselling was able to improve
      tenderness upon masticatory muscle palpation and maximum mouth opening with and
      without pain in patients with TMD, with similar results to those of interocclusal
      appliances approaches. Thus, counselling- and self-management-based therapies
      could be considered a conservative low-cost and beneficial treatment alternative
      for treating TMD to potentially improve psychological domains and remove harmful
      behaviours for the control of the signs and symptoms of TMD. 

PMID- 24102693
TI  - Molecular mechanisms linking the evolutionary conserved TORC1-Sch9 nutrient
      signalling branch to lifespan regulation in Saccharomyces cerevisiae.
AB  - The knowledge on the molecular aspects regulating ageing in eukaryotic organisms
      has benefitted greatly from studies using the budding yeast Saccharomyces
      cerevisiae. Indeed, many aspects involved in the control of lifespan appear to be
      well conserved among species. Of these, the lifespan-extending effects of calorie
      restriction (CR) and downregulation of nutrient signalling through the target of
      rapamycin (TOR) pathway are prime examples. Here, we present an overview on the
      molecular mechanisms by which these interventions mediate lifespan extension in
      yeast. Several models have been proposed in the literature, which should be seen
      as complementary, instead of contradictory. Results indicate that CR mediates a
      large amount of its effect by downregulating signalling through the TORC1-Sch9
      branch. In addition, we note that Sch9 is more than solely a downstream effector
      of TORC1, and documented connections with sphingolipid metabolism may be
      particularly interesting for future research on ageing mechanisms. As Sch9
      comprises the yeast orthologue of the mammalian PKB/Akt and S6K1 kinases, future
      studies in yeast may continue to serve as an attractive model to elucidate
      conserved mechanisms involved in ageing and age-related diseases in humans. 

PMID- 24102694
TI  - Diabetes mellitus and abnormalities in semen analysis.
AB  - AIM: The aim of this study was to compare the semen parameters of diabetic
      husbands of infertile couples with those of non-diabetic husbands of proven
      fertility. MATERIAL AND METHODS: Assuming a 5% fall in DNA integrity of sperms
      would affect fertility, the required sample size calculated was 103, with 80%
      power and 5% level of significance. During the study period (January 2010 to May
      2012), 52 husbands were found to have diabetes mellitus, by 2-h/post 75 g of
      glucose load (>= 200 mg %). Glycosylated hemoglobin level in each case was found
      to be more than 6.5% (study group). During the same period, six couples with
      infertility conceived spontaneously while undergoing evaluations, 60 couples
      conceived following treatment of ovulatory disorders in wives and all had ongoing
      pregnancies (more than 12 weeks). Husbands of these 66 couples were found to be
      non-diabetic (control group). Conventional semen analysis (World Health
      Organization criteria), hypo-osmotic swelling test and DNA integrity test
      (Acridine Orange test) were done in all cases. Body mass index was measured in
      each case. RESULTS: There were no differences in the mean age and body mass index
      between the two groups but significant differences were found in the following
      parameters: volume of the ejaculate (P = 0.004); total cells per ejaculate (P =
      0.01); percent motility (P = 0.0001); total motile cells per ejaculate (P =
      0.0001); percent of rapid progressive motility (P = 0.0001); percent normal
      morphology (P = 0.02); percent hypo-osmotic swelling test (0.0001); and percent
      normal DNA integrity (P = 0.0001). CONCLUSION: Diabetes mellitus can affect
      spermatogenesis at various levels, which can cause male-factor infertility.

PMID- 24102696
TI  - Copper-mediated dehydrogenative biaryl coupling of naphthylamines and 1,3-azoles.
AB  - A copper-mediated dehydrogenative biaryl cross-coupling of naphthylamines and 1,3
      azoles has been developed. The key to its success is the introduction of N,N
      bidentate coordination system based on the picolinamide directing group. The
      reaction proceeds smoothly without precious transition metal catalysts and
      provides highly pi-extended heterobiaryls directly. 

PMID- 24102695
TI  - Metagenomic 16S rDNA Illumina tags are a powerful alternative to amplicon
      sequencing to explore diversity and structure of microbial communities.
AB  - Sequencing of 16S rDNA polymerase chain reaction (PCR) amplicons is the most
      common approach for investigating environmental prokaryotic diversity, despite
      the known biases introduced during PCR. Here we show that 16S rDNA fragments
      derived from Illumina-sequenced environmental metagenomes (mi tags) are a
      powerful alternative to 16S rDNA amplicons for investigating the taxonomic
      diversity and structure of prokaryotic communities. As part of the Tara Oceans
      global expedition, marine plankton was sampled in three locations, resulting in
      29 subsamples for which metagenomes were produced by shotgun Illumina sequencing
      (ca. 700 Gb). For comparative analyses, a subset of samples was also selected for
      Roche-454 sequencing using both shotgun (m454 tags; 13 metagenomes, ca. 2.4 Gb)
      and 16S rDNA amplicon (454 tags; ca. 0.075 Gb) approaches. Our results indicate
      that by overcoming PCR biases related to amplification and primer mismatch, mi
      tags may provide more realistic estimates of community richness and evenness than
      amplicon 454 tags. In addition, mi tags can capture expected beta diversity
      patterns. Using mi tags is now economically feasible given the dramatic reduction
      in high-throughput sequencing costs, having the advantage of retrieving
      simultaneously both taxonomic (Bacteria, Archaea and Eukarya) and functional
      information from the same microbial community. 

PMID- 24102698
TI  - Ash dieback in the UK: a wake-up call.

PMID- 24102697
TI  - Rhythm-symptom correlation in patients on continuous monitoring after catheter
      ablation of atrial fibrillation.
AB  - INTRODUCTION: Correlation between symptoms and atrial fibrillation (AF) episodes
      after catheter ablation may have clinical relevance, especially for
      anticoagulation usage. The aim of our project was to analyze the relationship
      between symptoms and AF recurrences in unselected patients following AF catheter
      ablation during long-term follow-up. METHODS AND RESULTS: One hundred and forty
      three consecutive patients (mean age 59 +/- 9 years, 85% male) were implanted
      with a continuous cardiac monitor (RevealXT, Medtronic Inc., Minneapolis, MN,
      USA) following first pulmonary vein ablation procedure. Device data were
      downloaded every 3 months and correlated to patients' symptom diary. AF was
      paroxysmal in 55% and persistent in 45%. At a mean follow-up of 14 +/- 6 months,
      98/143 (69%) patients had at least one AF recurrence. Among these, 53 (54%)
      reported AF-related symptoms while 45 (46%) were totally asymptomatic.
      Conversely, 13 (29%) out of 45 patients without AF recurrences reported symptoms.
      Globally, a significant reduction of symptoms (from 82% at baseline to 44% at
      last follow-up; P < 0.0001) was observed. SF-12 questionnaire showed a
      significant improvement of physical and mental functioning (respectively 44.5 +/-
      8.5 vs 51.0 +/- 6.7, and 45.7 +/- 9.3 vs 49.2 +/- 6.1, P < 0.05 baseline vs last
      follow-up). At the 12-month follow-up, 80% and 77% of patients were on AAD and
      anticoagulant drugs, respectively. There were not differences in AAD usage in
      symptomatic and asymptomatic patients. CONCLUSIONS: Continuous ECG monitoring is
      a valuable tool for long-term follow-up after AF catheter ablation facilitating
      reliable assessment of symptomatic and asymptomatic AF episodes. This may have
      clinical implications with regards to anticoagulation therapy in high-risk
      patients.

PMID- 24102699
TI  - Spiritual care of the child with cancer at the end of life: a concept analysis.
AB  - AIM: The aim of this paper is to report an analysis of the concept of spiritual
      care of a child with cancer at the end of life. BACKGROUND: Spirituality is a
      vital dimension of a child's experience at the end of life; providing comfort;
      support; and a sense of connection. Spiritual care is paramount to address the
      substantial spiritual distress that may develop. DESIGN: Rodgers' method of
      evolutionary concept analysis guided the review process. DATA SOURCES: The
      literature search was not limited by start date and literature through the end of
      2012 was included. English, peer-reviewed texts in the databases CINAHL, ATLA and
      PubMed were included. METHODS: Critical analysis of the literature identified
      surrogate terms, related concepts, attributes, antecedents and consequences.
      RESULTS: The analysis identified six attributes: assessing spiritual needs;
      assisting the child to express feelings; guiding the child in strengthening
      relationships; helping the child to be remembered; assisting the child to find
      meaning; and aiding the child to find hope. Antecedents include existential
      questions and spiritual distress. Consequences include a peaceful death,
      spiritual growth, a relationship of trust and enhanced end-of-life care.
      CONCLUSION: Spiritual care is a vital aspect of holistic nursing care; however,
      gaps in knowledge and practice prevent children from receiving adequate spiritual
      care at the end of life. Nurses would benefit from increased awareness, skills
      and knowledge about spiritual care. Research is needed to identify interventions
      that exert the greatest effect on patient care outcomes.

PMID- 24102700
TI  - The epithelium specific cell cycle regulator 14-3-3sigma is required for
      preventing entry into mitosis following ultraviolet B.
AB  - BACKGROUND: Deoxyribonucleic acid damage activates cell cycle checkpoints in
      order to maintain genomic stability. We assessed the role of different checkpoint
      genes in response to ultraviolet B irradiation. METHODS: Cell lines expressing a
      dominant negative mutant of ataxia telangiectasia and Rad3 related (Atr) protein
      or overexpressing Cdc25A, cells deficient for 14-3-3sigma, Nijmegen breakage
      syndrome (Nbs), or Ataxia telangiectasia mutated (Atm) were treated with
      ultraviolet B (UVB) and harvested after 12 h, 24 h, or 48 h for analysis by flow
      cytometry. RESULTS: Functional loss of Atm, Atr, or Nbs did not result in a
      significant alteration of the cell cycle profile. Overexpression of Cdc25A led to
      a delayed arrest at the G1/S transition in response to low doses of UVB. Loss of
      14-3-3sigma, a negative cell cycle regulator and downstream target of p53, caused
      a transient arrest at the G2/M boundary. CONCLUSIONS: Loss of 14-3-3sigma
      sensitizes cells to UVB. After a transient cell cycle arrest, 14-3-3sigma
      deficient cells die by undergoing mitotic catastrophe. Cdc25A overexpression
      causes a delayed arrest in response to low doses of UVB. After higher doses,
      Cdc25A is no longer able to overrun the checkpoint. Atm, Atr, or Nbs are not
      essential for the checkpoint response to UVB, suggesting the existence of
      redundant signaling pathways.

PMID- 24102701
TI  - Brazilian obesity prevention and control initiatives.
AB  - Obesity prevalence in the Brazilian adult population is 12.5% among men and 16.9%
      among women. Obesity control has been a subject of concern in Brazilian health
      policies since the publication of the National Food and Nutrition Policy in 1999.
      The initiatives include a comprehensive national intersectorial plan for obesity
      prevention and control focused on confronting its social and environmental
      causes, development of a food and nutrition education framework aimed at
      intersectorial public policies in the food and nutritional security field,
      promotion and provision of healthy food in school environments (linked to family
      farming), structuring nutrition actions in primary healthcare in the national
      healthcare system, promoting community physical activity, food regulation and
      control, and encouragement of public participation and food control. We conclude
      that several initiatives have been developed in Brazil to deal with the challenge
      of implementing an intergovernmental, intersectorial response to reverse the
      rising overweight and obesity rates. The success of this response will depend on
      a governance model that promotes joint and integrated action by different sectors
      and active participation of society to consolidate the actions, places and laws
      that protect health and promote healthy lifestyles. 

PMID- 24102702
TI  - Parallel development of ERP and behavioural measurements of visual segmentation.
AB  - Visual segmentation, a process in which elements are integrated into a form and
      segregated from the background, is known to differ from adults at infancy. The
      further developmental trajectory of this process, and of the underlying brain
      mechanisms, during childhood and adolescence is unknown. The aim of the study was
      to investigate the developmental trajectory of ERP reflections of visual
      segmentation, and to relate this to behavioural performance. One hundred and
      eleven typically developing children from 7 to 18 years of age were divided into
      six age groups. Each child performed two visual tasks. In a texture segmentation
      task, the difference in event-related potential (ERP) response to homogeneous (no
      visual segmentation) and checkered stimuli (visual segmentation) was
      investigated. In addition, behavioural performance on integration of elements
      into contours was measured. Both behavioural and ERP measurements of visual
      segmentation differed from adults in 7-12 year-old children. Behaviourally, young
      children were less able to integrate elements into a contour than older children.
      In addition, a developmental change was present in the ERP pattern evoked by
      homogeneous versus checkered stimuli. The largest differences in behaviour and
      ERPs were found between 7-8- and 9-10-, and between 11-12- and 13-14-year-old
      children, indicating the strongest development between those age groups.
      Behavioural as well as ERP measurements at 13-14 years of age showed similar
      results to those of adults. These results reveal that visual segmentation
      continues to develop until early puberty. Only by 13-14 years of age, children do
      integrate and segregate visual information as adults do. These results can be
      interpreted in terms of functional connectivity within the visual cortex. 

PMID- 24102703
TI  - Alveolar ridge and maxillary sinus augmentation using rhBMP-2: a systematic
      review.
AB  - PURPOSE: The aim of this systematic review was to evaluate clinical and safety
      data for recombinant human bone morphogenetic protein-2 (rhBMP-2) in an
      absorbable collagen sponge (ACS) carrier when used for alveolar ridge/maxillary
      sinus augmentation in humans. MATERIALS AND METHODS: Clinical studies/case series
      published 1980 through June 2012 using rhBMP-2/ACS were searched. Studies meeting
      the following criteria were considered eligible for inclusion: >10 subjects at
      baseline and maxillary sinus or alveolar ridge augmentation not concomitant with
      implant placement. RESULTS: Seven of 69 publications were eligible for review.
      rhBMP-2/ACS yielded clinically meaningful bone formation for maxillary sinus
      augmentation that would allow placement of regular dental implants without
      consistent differences between rhBMP-2 concentrations. Nevertheless, the
      statistical analysis showed that sinus augmentation following autogenous bone
      graft was significantly greater (mean bone height: 1.6 mm, 95% CI: 0.5-2.7 mm)
      than for rhBMP-2/ACS (rhBMP-2 at 1.5 mg/mL). In extraction sockets, rhBMP-2/ACS
      maintained alveolar ridge height while enhancing alveolar ridge width. Safety
      reports did not represent concerns for the proposed indications. CONCLUSIONS:
      rhBMP-2/ACS appears a promising alternative to autogenous bone grafts for
      alveolar ridge/maxillary sinus augmentation; dose and carrier optimization may
      expand its efficacy, use, and clinical application.

PMID- 24102704
TI  - Discharge phone calls: a technique to improve patient care during the transition
      from hospital to home.
AB  - The discharge process is a transitional period when the patient's care is shifted
      from the hospital to the home and can be stressful for patients. One technique
      used to improve the quality and continuity of care is the discharge phone call
      (DPC). A large, metropolitan hospital implemented the DPC program to improve
      quality of care and decrease readmission rates. Qualitative interviews were
      performed with 24 hospital leaders, managers, and staff to determine the impact
      of the DPC program on the quality of care during the discharge process.
      Interviewees responded that the main benefits to the DPCs related to patient's
      medication management, follow-up appointment reminders, and answering questions.
      From a hospital perspective, the DPC can provide feedback to help improve the
      care delivery process related to discharge planning through improved discharge
      instructions and reinforcement of prescribed steps upon the patient's return
      home. 

PMID- 24102705
TI  - Flow mapping inside a left ventricular aneurism: a potential tool to demonstrate
      thrombogenicity.
AB  - We describe the use of vector flow mapping (VFM), a novel echocardiographic
      technique allowing intracardiac flow visualization, to quantify flow intensity
      inside a left ventricular aneurysm in a 68-year-old man. VFM successfully
      identified areas of stagnant flow corresponding to the wall region where a
      thrombus had been formed. 

PMID- 24102706
TI  - Factors influencing job satisfaction among registered nurses: a questionnaire
      survey in Mashhad, Iran.
AB  - BACKGROUND: Job satisfaction is a critical factor in health care. Strong
      empirical evidence supports a causal relationship between job satisfaction,
      patient safety and quality of care. OBJECTIVE: To determine the level of nurses'
      job satisfaction and its associated factors. METHOD: A stratified random sample
      of 421 registered nurses working at a large hospital in Mashhad, Iran was
      surveyed. RESULT: The results showed that autonomy, task requirement and work
      interaction had scores higher than their respective median on the subscales.
      There were significant differences between demographic characteristics and the
      autonomy, task requirement, work interaction, salary, work condition,
      professional development, supportive nursing management, decision making,
      professional status subscales and mean total job satisfaction. In univariate
      analysis, young age, being female and being married were significantly associated
      with a higher level of job satisfaction. The adjusted R(2) for this model was
      0.14, indicating that the model explained 14% of the variability. The regression
      model was highly significant, F (4298) = 13.194, P < 0.001. CONCLUSIONS AND
      IMPLICATIONS FOR NURSING MANAGEMENT: The authors emphasise that the human
      resources policies and incentives need to be re-visited. Efforts undertaken to
      improve working conditions, supportive nursing management, improved professional
      status, professional development and increased salaries are some of the ways for
      nurse managers to improve job satisfaction.

PMID- 24102707
TI  - Isolation and characterization of five lytic bacteriophages infecting a Vibrio
      strain closely related to Vibrio owensii.
AB  - Vibrio owensii is a potential bacterial pathogen in marine aquaculture system. In
      this study, five lytic phages specific against Vibrio strain B8D, closely related
      to V. owensii, were isolated from seawater of an abalone farm. The phages were
      characterized with respect to morphology, genome size, growth phenotype, as well
      as thermal, and pH stability. All phages were found to belong to the family
      Siphoviridae with long noncontractile tails and terminal fibers. Restriction
      analysis indicated that the five phages were dsDNA viruses with molecular weights
      ranging from c. 30 to 48 kb. One-step growth experiments revealed that the phages
      were heterogeneous in latent periods (10-70 min), rise periods (40-70 min), and
      burst sizes [23-331 plaque-forming units (PFU) per infected cell] at the same
      host strain. All phages were thermal stable and were tolerant to a wide range of
      pH. The results indicated that these phages could be potential candidates of a
      phage cocktail for biological control of V. owensii in aquaculture systems.

PMID- 24102708
TI  - Effect of mode of delivery on postpartum depression in Iranian women.
AB  - AIM: The aim of this study was to determine the relation between mode of delivery
      (cesarean section [CS] or unassisted vaginal delivery) and postpartum depression
      (PPD). MATERIAL AND METHODS: In a prospective study, 300 women who had
      experienced vaginal delivery (VD) or CS were recruited in Kashan, Iran. PPD was
      measured using the Edinburgh Postnatal Depression Scale (EPDS). A score of 13 or
      more was defined as PPD. Data collection was conducted at two assessment points:
      2 months and 4 months postpartum. Mean scores of EPDS and PPD were compared
      between the VD and CS groups. RESULTS: Differences in mean scores of EPDS between
      CS (n = 150) and VD (n = 150) groups at the first and the second assessments were
      not significant. The depression mean scores differences from the first to the
      second assessment were compared between the two groups; VD group showed more
      decrease on EPDS score (P = 0.006). Comparing the two assessments, the VD group
      showed a more decreased EPDS from the first to the second one. PPD prevalence
      rates (score >= 13) among the VD and CS groups were 24% and 20.7% for the first
      and 14.7% and 16.7% for the second assessment, respectively, which were not
      significantly different. The logistic regression showed that an unwanted
      pregnancy and PPD 2 months after delivery were determinants for PPD 4 months
      after delivery. CONCLUSION: There was no relation between delivery mode and PPD
      at 2 and 4 months after delivery; however, the VD group showed greater decrease
      in EPDS score from 2 to 4 months after delivery.

PMID- 24102709
TI  - Endoscopic ultrasonography-guided cholecystogastrostomy in patients with
      unresectable pancreatic cancer using anti-migratory metal stents: a new approach.
AB  - Cholecystectomy is contraindicated in patients with comorbidities or unresectable
      cancer. Percutaneous transhepatic gallbladder drainage (PTGBD) is typically
      offered with response rates ranging from 56% to 100%, but has several risks such
      as bleeding, pneumothorax, pneumoperitoneum, bile leak, and/or catheter
      migration. Endoscopic transpapillary gallbladder drainage (ETGD) and endoscopic
      ultrasound-guided transmural gallbladder drainage (EUS-GBD) are alternative
      endoscopic modalities that have a technical feasibility, efficacy and safety
      profile comparable with PTGBD. In this report, we present the first case series
      of transgastric EUS-GBD with placement of a fully covered self-expandable metal
      stent with anti-migratory fins. In three pancreatic cancer cases with acute
      cholecystitis when ETGD was unsuccessful, there were no bile leaks or
      procedurally related complications. There were no acute cholecystitis
      recurrences. In conclusion, EUS-GBD is a promising, minimally invasive treatment
      for acute cholecystitis. Additional comparative studies are needed to validate
      the benefit of this technique.

PMID- 24102710
TI  - Regulators with potential: substantiating myeloid-derived suppressor cells in
      human organ transplantation.

PMID- 24102711
TI  - Population genomic footprints of selection and associations with climate in
      natural populations of Arabidopsis halleri from the Alps.
AB  - Natural genetic variation is essential for the adaptation of organisms to their
      local environment and to changing environmental conditions. Here, we examine
      genomewide patterns of nucleotide variation in natural populations of the
      outcrossing herb Arabidopsis halleri and associations with climatic variation
      among populations in the Alps. Using a pooled population sequencing (Pool-Seq)
      approach, we discovered more than two million SNPs in five natural populations
      and identified highly differentiated genomic regions and SNPs using FST -based
      analyses. We tested only the most strongly differentiated SNPs for associations
      with a nonredundant set of environmental factors using partial Mantel tests to
      identify topo-climatic factors that may underlie the observed footprints of
      selection. Possible functions of genes showing signatures of selection were
      identified by Gene Ontology analysis. We found 175 genes to be highly associated
      with one or more of the five tested topo-climatic factors. Of these, 23.4% had
      unknown functions. Genetic variation in four candidate genes was strongly
      associated with site water balance and solar radiation, and functional
      annotations were congruent with these environmental factors. Our results provide
      a genomewide perspective on the distribution of adaptive genetic variation in
      natural plant populations from a highly diverse and heterogeneous alpine
      environment. 

PMID- 24102712
TI  - Benefit of thrombolysis for stroke is maintained around the clock: results from
      the SITS-EAST Registry.
AB  - BACKGROUND AND PURPOSE: The outcome of thrombolysis for early morning and sleep
      time strokes may be worse because of uncertainty of stroke onset time or
      differences in logistics. The aim of the study was to analyze if stroke outcome
      after intravenous thrombolysis differs depending on time of day when the stroke
      occurs. METHODS: The data collected in the Safe Implementation of Treatments in
      Stroke - Eastern Europe (SITS-EAST) Registry between September 2000 and December
      2011 were used. Strokes were categorized as night-time 00:00-07:59, day-time
      08:00-15:59 and evening-time 16:00-23:59 and were compared in terms of several
      outcome measures. All results were adjusted for baseline differences. RESULTS: A
      total of 8878 patients were enrolled: 18% had night-time, 54% day-time and 28%
      evening-time strokes. Onset-to-treatment time in patients with night-time strokes
      was 10 min longer than in day-time and evening-time strokes (P < 0.001).
      Symptomatic intracerebral hemorrhage by ECASS II definition occurred in 5.6%,
      5.6% and 5.3% (adjusted P = 0.41) of the night-time, day-time and evening-time
      stroke patients, respectively; by SITS definition it occurred in 2.5%, 1.9% and
      1.3% (adjusted P = 0.013) and by NINDS definition in 7.8%, 7.6% and 7.5%
      (adjusted P = 0.74). Patients with night-time, day-time and evening-time strokes
      achieved modified Rankin Scale score 0-1 in 33%, 31%, 31% (adjusted P = 0.34) and
      0-2 in 52%, 51%, 50% (adjusted P = 0.23), and 13%, 15%, 16% respectively of
      patients died (adjusted P = 0.17) by 3 months. CONCLUSIONS: The time when stroke
      occurs (day versus evening versus night) does not affect the outcome after
      thrombolysis despite the fact that patients with night-time strokes have worse
      time management.

PMID- 24102713
TI  - Unusual burn injury due to application of white vinegar and aspirin mixture.
AB  - Traditional medicine remedies are believed to provide relief from pain;
      nevertheless, it can be a risky procedure if these remedies are prepared
      inappropriately. Here, we describe a patient who suffered from a split-thickness
      leg burn after applying a self-inflicted mixture consisting of white vinegar and
      aspirin prepared for knee pain. This case report highlights a rare cause of a
      chemical burn that could become more common with increasing use of traditional
      remedies worldwide. 

PMID- 24102714
TI  - Aging and sleep deprivation induce the unfolded protein response in the pancreas:
      implications for metabolism.
AB  - Sleep disruption has detrimental effects on glucose metabolism through pathways
      that remain poorly defined. Although numerous studies have examined the
      consequences of sleep deprivation (SD) in the brain, few have directly tested its
      effects on peripheral organs. We examined several tissues in mice for induction
      of the unfolded protein response (UPR) following acute SD. In young animals, we
      found a robust induction of BiP in the pancreas, indicating an active UPR. At
      baseline, pancreata from aged animals exhibited a marked increase in a pro
      apoptotic transcription factor, CHOP, that was amplified by SD, whereas BiP
      induction was not observed, suggesting a maladaptive response to cellular stress
      with age. Acute SD increased plasma glucose levels in both young and old animals.
      However, this change was not overtly related to stress in the pancreatic beta
      cells, as plasma insulin levels were not lower following acute SD. Accordingly,
      animals subjected to acute SD remained tolerant to a glucose challenge. In a
      chronic SD experiment, young mice were found to be sensitized to insulin and have
      improved glycemic control, whereas aged animals became hyperglycemic and failed
      to maintain appropriate plasma insulin concentrations. Our results show that both
      age and SD cooperate to induce the UPR in pancreatic tissue. While changes in
      insulin secretion are unlikely to play a major role in the acute effects of SD,
      CHOP induction in pancreatic tissues suggests that chronic SD may contribute to
      the loss or dysfunction of endocrine cells and that these effects may be
      exacerbated by normal aging. 

PMID- 24102715
TI  - Poisons, toxungens, and venoms: redefining and classifying toxic biological
      secretions and the organisms that employ them.
AB  - Despite extensive study of poisonous and venomous organisms and the toxins they
      produce, a review of the literature reveals inconsistency and ambiguity in the
      definitions of 'poison' and 'venom'. These two terms are frequently conflated
      with one another, and with the more general term, 'toxin.' We therefore clarify
      distinctions among three major classes of toxins (biological, environmental, and
      anthropogenic or man-made), evaluate prior definitions of venom which
      differentiate it from poison, and propose more rigorous definitions for poison
      and venom based on differences in mechanism of delivery. We also introduce a new
      term, 'toxungen', thereby partitioning toxic biological secretions into three
      categories: poisons lacking a delivery mechanism, i.e. ingested, inhaled, or
      absorbed across the body surface; toxungens delivered to the body surface without
      an accompanying wound; and venoms, delivered to internal tissues via creation of
      a wound. We further propose a system to classify toxic organisms with respect to
      delivery mechanism (absent versus present), source (autogenous versus
      heterogenous), and storage of toxins (aglandular versus glandular). As examples,
      a frog that acquires toxins from its diet, stores the secretion within cutaneous
      glands, and transfers the secretion upon contact or ingestion would be
      heteroglandular-poisonous; an ant that produces its own toxins, stores the
      secretion in a gland, and sprays it for defence would be autoglandular
      toxungenous; and an anemone that produces its own toxins within specialized cells
      that deliver the secretion via a penetrating wound would be autoaglandular
      venomous. Adoption of our scheme should benefit our understanding of both
      proximate and ultimate causes in the evolution of these toxins.

PMID- 24102716
TI  - The structurally related auxin and melatonin tryptophan-derivatives and their
      roles in Arabidopsis thaliana and in the human malaria parasite Plasmodium
      falciparum.
AB  - Indole compounds are involved in a range of functions in many organisms. In the
      human malaria parasite Plasmodium falciparum, melatonin and other tryptophan
      derivatives are able to modulate its intraerythrocytic cycle, increasing the
      schizont population as well as parasitemia, likely through ubiquitin-proteasome
      system (UPS) gene regulation. In plants, melatonin regulates root development, in
      a similar way to that described for indoleacetic acid, suggesting that melatonin
      and indoleacetic acid could co-participate in some physiological processes due to
      structural similarities. In the present work, we evaluate whether the chemical
      structure similarity found in indoleacetic acid and melatonin can lead to similar
      effects in Arabidopsis thaliana lateral root formation and P. falciparum cell
      cycle modulation, as well as in the UPS of gene regulation, by qRT-PCR. Our data
      show that P. falciparum is not able to respond to indoleacetic acid either in the
      modulation of the intraerythrocytic cycle or in the gene regulation mediated by
      the UPS as observed for melatonin. The similarities of these indole compounds are
      not sufficient to confer synergistic functions in P. falciparum cell cycle
      modulation, but could interplay in A. thaliana lateral root formation. 

PMID- 24102718
TI  - Cervical column posture and airway dimensions in clinical bruxist adults: a
      preliminary study.
AB  - The aim of this study was to compare the cervical column posture and the upper
      airway dimensions between sleep bruxist and non-bruxist young adults. Twenty
      three sleep-grinders and 22 asymptomatic subjects, selected according to the
      American Academy of Sleep Medicine (AASM) criteria (report by a sleep partner and
      the presence of dental wear, according to Wetselaar et al.), were evaluated. The
      mean age was 23.8 years (range 18-30). All the subjects had complete permanent
      dentition and skeletal and occlusal class I. A digital cephalometric radiograph
      with natural head posture was performed for each subject. The craniocervical
      posture was traced and evaluated according to Solow and Tallgren, and the airway
      dimensions of the oropharynx and nasopharynx were evaluated in agreement with
      Sayinsu. The data were analysed with independent-samples t-tests and Mann-Whitney
      U-test. Significance was set at P < 0.05. Sleep bruxist young adults presented
      more forwarded cervical column posture and narrower measures of the oropharynx,
      when compared with controls (P < 0.05). As in children, anterior cervical column
      posture was found to be associated with sleep bruxism. 

PMID- 24102717
TI  - New dynamics in global obesity facing low- and middle-income countries.
AB  - Levels of overweight and obesity across low- and middle-income countries (LMIC)
      have approached levels found in higher-income countries. This is particularly
      true in the Middle East and North Africa and in Latin America and the Caribbean.
      Using nationally representative samples of women aged 19-49, n = 815,609, this
      paper documents the annualized rate of increase of overweight from the first
      survey in early 1990 to the last survey in the present millennium. Overweight
      increases ranged from 0.31% per year to 0.92% per year for Latin America and the
      Caribbean and for the Middle East and North Africa, respectively. For a sample of
      eight countries, using quantile regression, we further demonstrate that mean body
      mass index (BMI) at the 95th percentile has increased significantly across all
      regions, representing predicted weight increases of 5-10 kg. Furthermore we
      highlight a major new concern in LMICs, documenting waist circumference increases
      of 2-4 cm at the same BMI (e.g. 25) over an 18-year period. In sum, this paper
      indicates growing potential for increased cardiometabolic problems linked with a
      large rightward shift in the BMI distribution and increased waist circumference
      at each BMI level.

PMID- 24102719
TI  - Evaluation of risk factors for prediction of outcome in fetal spectrum of
      atrioventricular septal defects.
AB  - BACKGROUND: Atrioventricular septal defects (AVSD) are very commonly diagnosed in
      utero. Heterotaxy/chromosomal abnormalities frequently coexist with AVSD.
      However, outcomes of fetal AVSD are not precisely known. We attempted to define
      mortality risk factors in AVSD. METHOD: We retrospectively searched our database,
      electronic records, and echocardiograms with diagnosis of fetal AVSD from 2003 to
      2012. We investigated the following risk factors: atrial situs, heart
      rate/rhythm, ventricular dominance/morphology, atrioventricular valve
      regurgitation, cardiothoracic ratio, ejection fraction, and extracardiac
      anomalies. RESULTS: Forty-five fetuses with a median gestational age of 28 weeks
      (17.5-37.1) were determined to have AVSD during the 10 years, of which 12 were
      either lost to follow-up (6) or underwent termination (6). There were 16 deaths
      (48%); two died in utero. Isomerism was identified in 17 of 45 (37%) fetuses (11
      left atrial, 6 right atrial isomerism) and chromosomal abnormalities were
      identified in 12 (27%). Twenty-eight of 33 fetuses, not lost to follow-up or
      terminated, had extracardiac anomalies which had associated increased mortality
      (57% vs. 0%, P = .04). Heart block (75% vs. 43%, P = .12), left ventricular
      noncompaction (80% vs. 43%, P = .17), and isomerism (63% vs. 41%, P = .28) were
      associated with mortality but without statistical significance. Twenty-five of 45
      (56%) had unbalanced AVSD. Positional abnormalities of the great arteries or
      semilunar valve stenosis were present in 20/45 (44%) while venous anomalies were
      present in 16/45 (36%). Presence of ventricular dominance, atrioventricular valve
      regurgitation, elevated cardiothoracic ratio, or diminished ejection fraction
      were not associated with mortality. CONCLUSION: Overall mortality rate for
      fetuses with AVSD was 48%. The presence of extracardiac anomalies is an
      independent risk factor for prediction of fetal or neonatal demise. Heart block,
      isomerism, and noncompaction in fetal AVSD appear to be associated with poor
      outcomes as well but did not reach statistical significance. This information is
      useful for counseling parents with fetus AVSD.

PMID- 24102720
TI  - Flexural impact force absorption of mouthguard materials using film sensor
      system.
AB  - PURPOSE: Several methods have been used to measure the impact force absorption
      capacities of mouthguard materials; however, the relationships among these
      measurement systems have not been clearly determined. The purpose of the present
      study was to evaluate the impact force-absorbing capability of materials using a
      drop-ball system with film sensors and load cells to clarify the relationship
      between these two sensor systems. MATERIALS AND METHODS: Disk-shaped specimens
      (1, 2, and 3 mm thick) were prepared using three commercial thermoplastic
      mouthguard materials (Bioplast, Impact Guard, MG 21) and one experimental
      mouthguard material [mixture of Poly (ethyl methacrylate)]. Impact force was
      applied by letting a stainless steel ball drop free-fall onto the specimens and
      then measuring the impact load under each specimen using a film sensor system and
      a load cell sensor system. RESULTS: The total load measured with the film sensor
      system decreased with an increase in mouthguard thickness, while almost none of
      the transmitted impact forces measured with the load cell system were
      statistically different. CONCLUSIONS: The film sensor system was considered to be
      superior to the load cell system because the maximum stress and stress area could
      be determined.

PMID- 24102721
TI  - RhoD binds the Rab5 effector Rabankyrin-5 and has a role in trafficking of the
      platelet-derived growth factor receptor.
AB  - RhoD is a member of the classical Rho GTPases and it has essential roles in the
      regulation of actin dynamics. RhoD localizes to early endosomes and recycling
      endosomes, which indicates its important role in the regulation of endosome
      trafficking. Here, we show that RhoD binds to the Rab5 effector Rabankyrin-5, and
      RhoD and Rabankyrin-5 colocalize to Rab5-positive endosomes, which suggests a
      role for Rabankyrin-5 in the coordination of RhoD and Rab5 in endosomal
      trafficking. Interestingly, depletion of RhoD using siRNA techniques interfered
      with the internalization of the PDGFbeta receptor and the subsequent activation
      of the downstream signaling cascades. Our data suggest that RhoD and Rabankyrin-5
      have important roles in coordinating RhoD and Rab activities during
      internalization and trafficking of activated tyrosine kinase receptors. 

PMID- 24102722
TI  - Mobile genetic elements of Pseudomonas aeruginosa isolates from hydrotherapy
      facility and respiratory infections.
AB  - The content of mobile genetic elements in Pseudomonas aeruginosa isolates of a
      pristine natural mineral water system associated with healthcare was compared
      with clinical isolates from respiratory infections. One isolate, from the therapy
      pool circuit, presented a class 1 integron, with 100% similarity to a class 1
      integron contained in plasmid p4800 of the Klebsiella pneumoniae Kp4800 strain,
      which is the first time it has been reported in P. aeruginosa. Class 1 integrons
      were found in 25.6% of the clinical isolates. PAGI1 orf3 was more prevalent in
      environmental isolates, while PAGI2 c105 and PAGI3 sg100 were more prevalent in
      clinical isolates. Plasmids were not observed in either population.

PMID- 24102723
TI  - Different TRPV1-mediated brain responses to intragastric infusion of capsaicin
      and capsiate.
AB  - Capsaicin and capsiate, which is an analogue of capsaicin, are agonists of
      capsaicin-binding transient potential vanilloid 1 (TRPV1) receptors. However,
      their physiological effects are different. Capsaicin induces thermogenesis and
      nociception, while the different kinetics of capsiate result in thermogenesis
      without nociception in the oral cavity. In the present study, using functional
      magnetic resonance imaging, we compared the brain activation after intragastric
      infusion of non-nociceptive levels of capsaicin and capsiate in wild-type and
      TRPV1-knockout (KO) mice. Capsaicin activated several brain regions, such as the
      periaqueductal grey (PAG), thalamic nuclei and hypothalamus, including the medial
      preoptic area (mPOA) and ventromedial hypothalamus (VMH). Most of these areas
      were not activated in TRPV1-KO mice. Capsiate activated several regions,
      including the thalamic nuclei, mPOA and VMH but not PAG in wild-type mice. Most
      of the activated areas were not activated by intragastric capsiate infusion in
      TRPV1-KO mice. These results demonstrate that TRPV1 is critical for the induction
      of activation in the hypothalamus by capsaicin and capsiate, and these distinct
      brain activations could help to explain the individual physiological reactions of
      capsaicin and capsiate. 

PMID- 24102724
TI  - Targeted photochemotherapy in alopecia areata.
AB  - BACKGROUND/PURPOSE: Alopecia areata (AA) is a common cause of localized non
      scarring alopecia. Usage of targeted UVA after the topical application of 8
      methoxypsoralen (8-MOP) is one of the rising treatment modalities for AA. Our aim
      was to assess the efficacy and safety of topical 8-MOP plus targeted UVA
      phototherapy in the treatment of patchy AA. METHODS: Seven patchy AA patients
      were treated by topical 8-MOP application to the lesions followed by UVA
      irradiation 3 times a week, with 15 to 24 sessions in total. At the end of the
      treatment all patients were evaluated for response on a four-point scale (0 = no
      hair, 1 = white vellus hair, 2 = regrowth cosmetically acceptable for the
      patient, 3 = complete hair growth). RESULTS: The mean cumulative UVA dose was
      from 7.5 to 39.6 J/cm(2) . For all 7 patients, average response score was
      calculated as 2, which means cosmetically acceptable regrowth. CONCLUSION:
      Targeted UVA phototherapy combined with topical 8-MOP may be an effective and
      safe alternative treatment protocol for patchy AA, which should be kept in mind
      in order to choose the best for the patient, especially for patients incompatible
      with other treatments that are systemic and invasive.

PMID- 24102725
TI  - Factors associated with low back pain changes during the third trimester of
      pregnancy.
AB  - AIMS: (1) To investigate the course of pregnancy-related low back pain intensity
      and interference during the third trimester, and (2) to identify risk factors
      associated with changes in pain intensity and interference over time. BACKGROUND:
      Pregnancy-related low back pain is common and reaches its peak both in the
      prevalence and severity in the third trimester. DESIGN: A longitudinal design
      with consecutive sampling. METHODS: Three waves of data were collected from
      pregnant women in an antenatal care centre of a medical centre and a regional
      hospital in the northern Taiwan from February-June, 2010. Questionnaires were
      administered at gestational ages 28, 32 and 36 weeks. 214 women were enrolled and
      179 participants completed all measures. Generalized estimating equations were
      used to identify the risk factors associated with changes in pain intensity and
      pain interference over time. RESULTS: Pain interference increased over time
      during the third trimester. Pain catastrophizing and pain intensity at
      gestational age 24 weeks and time (from 28-36 weeks) were associated with
      increases in pregnancy-related low back pain intensity. These same factors plus
      depression were associated with an increase in pregnancy-related low back pain
      interference. CONCLUSIONS: This study identified a number of prospective factors
      related to increases in pain intensity and pain interference during the third
      trimester. Given that both catastrophizing and depression are modifiable, the
      findings indicate that research examining the benefits of treatments that address
      these (e.g. cognitive-behavioural therapy) on pain and pain interference is
      warranted.

PMID- 24102726
TI  - Systematic gene deletions evidences that laccases are involved in several stages
      of wood degradation in the filamentous fungus Podospora anserina.
AB  - Transformation of plant biomass into biofuels may supply environmentally friendly
      alternative biological sources of energy. Laccases are supposed to be involved in
      the lysis of lignin, a prerequisite step for efficient breakdown of cellulose
      into fermentable sugars. The role in development and plant biomass degradation of
      the nine canonical laccases belonging to three different subfamilies and one
      related multicopper oxidase of the Ascomycota fungus Podospora anserina was
      investigated by targeted gene deletion. The 10 genes were inactivated singly, and
      multiple mutants were constructed by genetic crosses. lac6(Delta), lac8(Delta)
      and mco(Delta) mutants were significantly reduced in their ability to grow on
      lignin-containing materials, but also on cellulose and plastic. Furthermore,
      lac8(Delta), lac7(Delta), mco(Delta) and lac6(Delta) mutants were defective
      towards resistance to phenolic substrates and H2 O2 , which may also impact
      lignocellulose breakdown. Double and multiple mutants were generally more
      affected than single mutants, evidencing redundancy of function among laccases.
      Our study provides the first genetic evidences that laccases are major actors of
      wood utilization in a fungus and that they have multiple roles during this
      process apart from participation in lignin lysis.

PMID- 24102727
TI  - Catheter-tissue contact force determines atrial electrogram characteristics
      before and lesion efficacy after antral pulmonary vein isolation in humans.
AB  - INTRODUCTION: Electrogram (EGM) characteristics are used to infer catheter-tissue
      contact. We examined if (a) atrial EGM characteristics predicted CF and (b)
      compared the value of CF versus other surrogates for predicting lesion efficacy.
      METHODS AND RESULTS: Twelve paroxysmal AF patients underwent pulmonary vein
      isolation using radiofrequency (RF) ablation facilitated by a novel CF-sensing
      catheter. Operators were blinded to CF. EGM amplitude, width, and morphology were
      measured pre- and post-RF. At each RF site, average CF, force-time integral
      (FTI), impedance fall, time to impedance plateau, maximum power, catheter tip
      temperature, and total energy delivered were recorded. An effective lesion was
      defined based on previously validated EGM criteria for transmural lesions. There
      was a moderate correlation between CF and EGM amplitude (r = 0.19) and EGM width
      (r = -0.22). Pre-RF, EGM amplitude, and width had modest to poor discriminative
      capacity for identifying preablation CF (e.g., EGM amplitude identified CF>20 g
      with sensitivity and specificity of 67% and 60%, respectively). Preablation CF,
      FTI, and total energy delivered during RF were the only independent predictors of
      effective lesion formation. Neither pre-RF EGM amplitude/width nor power,
      temperature, and impedance changes during RF predicted effective lesion
      formation. An average CF >16 g or FTI >404 g*s had excellent sensitivity and
      specificity (>80%) for identifying an effective lesion. CONCLUSIONS: EGM
      characteristics do not reliably predict either CF before the onset of RF, nor do
      they predict the likelihood of an effective lesion. CF parameters were superior
      to power, temperature, and impedance changes during RF in predicting lesion
      efficacy.

PMID- 24102728
TI  - Maintaining goal blood pressures after switching from olmesartan to other
      angiotensin receptor blockers.
AB  - This study assessed blood pressure (BP) goal maintenance in patients controlled
      with olmesartan monotherapy after switching to another angiotensin type II
      receptor blocker (ARB). Hypertensive patients prescribed olmesartan monotherapy
      were identified from GE Healthcare's Centricity electronic medical record between
      2007 and 2011. After documentation of BP goal (<140/90 mm Hg) attainment,
      patients were placed into the continuation cohort if olmesartan monotherapy was
      maintained or into the switch cohort if they were changed to irbesartan,
      losartan, or valsartan. Follow-up assessments were the first BP measurement 28 to
      390 days after attaining BP goal (continuation cohort) or after prescribing an
      alternative ARB (switch cohort). Of 3412 patients included (3027 continuation
      cohort, 385 switch cohort), 52% were women and mean age was 58.0 years. In the
      switch cohort, 310 (80.5%) were switched to losartan (n=236), irbesartan (n=58),
      or valsartan (n=16) monotherapy and 75 (19.5%) were switched to combination
      antihypertensive therapy. Mean baseline and follow-up BP were 122.5/75.8 mm Hg
      and 126.6/77.6 mm Hg, respectively, in the continuation cohort (P<.001) and
      123.5/75.4 mm Hg and 129.6/78.5 mm Hg, respectively, in the switch cohort
      (P<.001). BP goal maintenance was 78.7% and 72.2% in the continuation and switch
      cohort, respectively (odds ratio, 0.707; 95% confidence interval, 0.555-0.899).
      Patients who continued on olmesartan monotherapy after attaining BP goal had a
      higher percentage of BP goal maintenance than patients who switched therapy. 

PMID- 24102729
TI  - Three-dimensional echocardiographic evaluation of a patient with double-orifice
      mitral valve, bicuspid aortic valve, and coarctation of aorta.
AB  - A 16-year-old male patient was diagnosed with bicuspid aortic valve and
      coarctation of aorta, and had a history of a subclavian patch plasty operation at
      1 year of age. In addition, we detected double-orifice mitral valve (DOMV) at a
      routine evaluation and demonstrated by both two-dimensional and three-dimensional
      (3D) echocardiographic examinations. DOMV should be kept in mind in cases with
      left ventricular obstructive lesions and 3D echocardiography may provide a more
      detailed assessment of mitral valve and subvalvular apparatus.

PMID- 24102730
TI  - Nurses aged over 50 years and their experiences of shift work.
AB  - AIM: The Late Career Nurse project examined views and characteristics of nurses
      working in New Zealand who were born before 1960. This paper focuses on the
      experiences of such nurses who undertake shift work. BACKGROUND: The mean age of
      registered nurses in New Zealand has been rising steadily, and 40% are now aged
      50 years or over. While there is substantial literature on the phenomenon and
      consequences of the ageing nursing workforce, little is known of the particular
      experiences of nurses aged over 50 years who work shifts. METHOD: An anonymous
      online survey was emailed to eligible nurse New Zealand Nurses Organisation
      members aged over 50 years in February 2012. Quantitative and qualitative
      analyses of the 3273 responses received were undertaken. RESULT: Over 45% of
      respondents worked shifts or flexible hours. While shift work suited many, others
      noted deleterious effects on family and social relationships, physical and mental
      health (notably sleep patterns and fatigue), and decreasing tolerance for shift
      work as they age. Poor scheduling practices were particularly detrimental.
      CONCLUSION AND IMPLICATIONS FOR NURSING MANAGEMENT: Worldwide, workforce ageing
      means strategies are required to retain older nurses in the workforce. Improved
      scheduling practices including increasing access to flexible and part time work
      hours, and development of resources on coping with shift work are recommended.

PMID- 24102731
TI  - Serum thymus and activation-regulated chemokine as disease activity and response
      biomarker in alopecia areata.
AB  - Serum thymus and activation-regulated chemokine/CCL17 (sTARC) is known as a good
      indicator for atopic dermatitis severity. Herein, we investigate whether sTARC
      correlates with severity and therapeutic response for alopecia areata (AA) in our
      121 patients. The sTARC mean of AA totalis and universalis was significantly
      higher than mild AA. Next, we compared sTARC of diffuse AA (n = 14) and severity
      controlled patchy AA (n = 32) and found that sTARC in diffuse AA (564.2 +/- 400.0
      pg/mL) was significantly higher than that of the patchy type (344.0 +/- 239.8
      pg/mL), suggesting a potential role of TARC in active progression of diffuse AA.
      Ten patients with diffuse AA were treated with i.v. corticosteroid pulse therapy.
      Then, we tested whether sTARC can predict prognosis after the pulse therapy and
      found that baseline sTARC in the poor responders (1025.5 +/- 484.8 pg/mL) was
      significantly higher than that in the good responders (complete remission at 24
      months after the pulse therapy, 347.8 +/- 135.7 pg/mL), indicating sTARC as a
      response biomarker in the corticosteroid pulse therapy for diffuse AA. Finally,
      to investigate TARC production in the affected hair follicles, we performed
      immunohistochemical double staining of TARC and CD68 using scalp skin specimens
      of diffuse AA with high titers of sTARC. The results showed their co-localization
      in the infiltrating cells around the AA hair follicles, suggesting that TARC is
      mainly produced from CD68(+) histiocytes. In conclusion, sTARC is a disease
      activity and response biomarker in AA, providing new insight beyond the T-helper
      1/2 paradigm to solve the immunological pathogenesis of AA.

PMID- 24102732
TI  - Prognostic significance of thrombocytosis, platelet parameters and aggregation
      rates in epithelial ovarian cancer.
AB  - AIM: The aim of this study is to investigate the impact of preoperative platelet
      counts, parameters and aggregation rates (maximal aggregation rate: MAR) on
      prognosis in patients with epithelial ovarian cancer (EOC). METHODS: Preoperative
      platelet count, parameters and MAR in 182 EOC patients, 122 patients with benign
      ovarian tumor and 150 healthy women were retrospectively analyzed. The
      correlation between thrombocytosis, platelet parameters, MAR and
      clinicopathological factors were evaluated in EOC. RESULTS: Forty-five (24.73%)
      EOC patients had preoperative thrombocytosis in this study. The mean platelet
      count in the EOC group was significantly higher than that of benign and healthy
      groups (P < 0.001). The MAR in the EOC group was significantly higher than that
      in the healthy group (71.96% vs 57.03%, P = 0.025). The platelet parameters (mean
      platelet volume, platelet distribution width, thrombocytocrit and large platelet
      ratio) were consistently higher in the EOC group than those in the benign and
      healthy groups, but the differences were insignificant. A significant correlation
      between thrombocytosis and MAR was observed in EOC patients (r = 0.694, P <
      0.001). EOC patients with thrombocytosis were found to have significantly higher
      grade (P = 0.048), more advanced stage (P = 0.045), higher level carbohydrate
      antigen-125 (P = 0.007) and greater likelihood of suboptimal cytoreduction (P =
      0.035). EOC patients with both thrombocytosis and high MAR were found to have
      shorter progression-free survival (P = 0.001)and overall survival (P = 0.004).
      The combination of thrombocytosis and MAR, as well as stage and optimal
      cytoreduction, retained significance as an independent prognostic factor for
      overall survival. CONCLUSION: Thrombocytosis, accompanied by increasing of
      platelet aggregation rates, is associated with more aggressive tumor biology in
      EOC. The combination of thrombocytosis and MAR is an independent negative
      prognostic factor for overall survival in EOC patients.

PMID- 24102733
TI  - Population incidence of Guillain-Barre syndrome in parts of China: three large
      populations in Jiangsu province, 2008-2010.
AB  - BACKGROUND AND PURPOSE: It is important to have an estimate of the incidence of
      Guillain-Barre syndrome (GBS) because of the expansion of vaccination programs
      and the associated risks of vaccine-related GBS. Incidence information in Asia,
      especially in China, is scarce. This study attempts to describe GBS incidence in
      large Chinese populations located in three geographically different and
      moderately distant areas of the same province. METHODS: The surveyed areas were
      Nanjing, Yancheng and Xuzhou, which are three cities in Jiangsu province in
      China. Nanjing is in the south of Jiangsu province, Yancheng is in the middle and
      Xuzhou is in the north. The survey was carried out in regions that might have
      received patients meeting the case definition from 2008 to 2010. The population
      numbers came from the local Bureau of Statistics. Data analysis was conducted in
      2011. RESULTS: The incidence of GBS was 0.59 cases per 100,000 person-years. The
      GBS incidence increased with age amongst people <80 years old. Males had a higher
      incidence of GBS than females. GBS incidence in Nanjing was the highest amongst
      the three regions. CONCLUSIONS: The incidence rates in parts of Jiangsu province
      were lower than those in Europe and North America. There was one peak in
      incidence amongst older adults (70-80 years). Geographical differences in GBS
      incidence rates may be related to socioeconomic status. There were no significant
      seasonal variations of incidence in Jiangsu.

PMID- 24102734
TI  - Inferior early posttransplant outcomes for recipients of right versus left
      deceased and living donor kidneys.

PMID- 24102735
TI  - Soft coagulation in partial nephrectomy without renorrhaphy: feasibility of a new
      technique and early outcomes.
AB  - OBJECTIVES: To study the feasibility of a new partial nephrectomy technique using
      soft coagulation without renorrhaphy. METHODS: Open partial nephrectomy using
      soft coagulation without renorrhaphy was carried out on 39 consecutive patients
      with renal tumors. The renal artery was clamped in the initial 23 cases (59%),
      whereas 16 surgeries (41%) were carried out without clamping. The resected
      surface of the kidney was coagulated solely by soft coagulation without
      renorrhaphy. Suturing was used only when the urinary collecting system was
      opened. The surgical results and perioperative complications were retrospectively
      evaluated. RESULTS: The mean age of patients was 63.1 years. The mean tumor size
      was 28.2 mm (range 10-56 mm). The mean RENAL nephrometry score was 8.03 (range 4
      10). The mean cold ischemic time (in clamped cases) was 25 min. The mean
      operative time was 193 min (range 113-310 min), and the mean estimated total
      blood loss was 172 mL (range 20-530 mL) in all cases. All operations were
      uneventful, and none required blood transfusion or conversion to nephrectomy.
      Postoperative complications, such as hemorrhage, urinary fistula formation and
      requirement of hemodialysis, were not observed. All patients had negative
      surgical margins, and were free of disease recurrence during the follow-up period
      (3-49 months). Overall, a remarkable decrease in renal function was not evident
      at the end of the follow-up period. CONCLUSIONS: This new technique using soft
      coagulation appears to be safe and feasible for partial nephrectomy.

PMID- 24102736
TI  - Population genomics from pool sequencing.
AB  - Next generation sequencing of pooled samples is an effective approach for studies
      of variability and differentiation in populations. In this paper we provide a
      comprehensive set of estimators of the most common statistics in population
      genetics based on the frequency spectrum, namely the Watterson estimator thetaW,
      nucleotide pairwise diversity Pi, Tajima's D, Fu and Li's D and F, Fay and Wu's
      H, McDonald-Kreitman and HKA tests and FST, corrected for sequencing errors and
      ascertainment bias. In a simulation study, we show that pool and individual theta
      estimates are highly correlated and discuss how the performance of the statistics
      vary with read depth and sample size in different evolutionary scenarios. As an
      application, we reanalyse sequences from Drosophila mauritiana and from an
      evolution experiment in Drosophila melanogaster. These methods are useful for
      population genetic projects with limited budget, study of communities of
      individuals that are hard to isolate, or autopolyploid species. 

PMID- 24102737
TI  - Ocular manifestation of lymphoma in newly diagnosed cats.
AB  - Ocular manifestations of lymphoma are described in humans and dogs but rarely in
      cats. In this prospective study, cats with newly diagnosed and treatment-naive
      lymphoma were evaluated concerning clinical stage and ophthalmologic findings.
      Twenty-six cats were included. In 12 cats (48%), ocular changes were documented.
      Uveitis anterior and posterior were predominant findings, being present in 58% of
      affected individuals. Other findings included exophthalmos, corneal surface
      lesions and chemosis. Eight cats received chemotherapy, two of which had ocular
      involvement. In these two cats, a complete remission of an anterior and a partial
      remission of a posterior uveitis were documented. Due to the detection of ocular
      involvement, a stage migration from stage IV to V occurred in four patients. In
      the light of these findings, an opthalmological examination may be considered as
      an important part of staging in feline lymphoma as well as of follow-up
      examination in affected cats. 

PMID- 24102738
TI  - Constitutive or seed-specific overexpression of Arabidopsis G-protein gamma
      subunit 3 (AGG3) results in increased seed and oil production and improved stress
      tolerance in Camelina sativa.
AB  - Heterotrimeric G-proteins consisting of Galpha, Gbeta and Ggamma subunits play an
      integral role in mediating multiple signalling pathways in plants. A novel,
      recently identified plant-specific Ggamma protein, AGG3, has been proposed to be
      an important regulator of organ size and mediator of stress responses in
      Arabidopsis, whereas its potential homologs in rice are major quantitative trait
      loci for seed size and panicle branching. To evaluate the role of AGG3 towards
      seed and oil yield improvement, the gene was overexpressed in Camelina sativa, an
      oilseed crop of the Brassicaceae family. Analysis of multiple homozygous T4
      transgenic Camelina lines showed that constitutive overexpression of AGG3
      resulted in faster vegetative as well as reproductive growth accompanied by an
      increase in photosynthetic efficiency. Moreover, when expressed constitutively or
      specifically in seed tissue, AGG3 was found to increase seed size, seed mass and
      seed number per plant by 15%-40%, effectively resulting in significantly higher
      oil yield per plant. AGG3 overexpressing Camelina plants also exhibited improved
      stress tolerance. These observations draw a strong link between the roles of AGG3
      in regulating two critical yield parameters, seed traits and plant stress
      responses, and reveal an effective biotechnological tool to dramatically increase
      yield in agricultural crops. 

PMID- 24102739
TI  - Irrigating methicillin-resistant Staphylococcus aureus-colonised and -infected
      chronic wounds - why use tap water?

PMID- 24102740
TI  - Feeding by heterotrophic dinoflagellates and ciliates on the free-living
      dinoflagellate Symbiodinium sp. (Clade E).
AB  - To investigate heterotrophic protists grazing on Symbiodinium sp., we tested
      whether the common heterotrophic dinoflagellates Gyrodinium dominans, Gyrodinium
      moestrupii, Gyrodinium spirale, Oblea rotundata, Oxyrrhis marina, and Polykrikos
      kofoidii and the ciliates Balanion sp. and Parastrombidinopsis sp. preyed on the
      free-living dinoflagellate Symbiodinium sp. (clade E). We measured the growth and
      ingestion rates of O. marina and G. dominans on Symbiodinium sp. as a function of
      prey concentration. Furthermore, we compared the results to those obtained for
      other algal prey species. In addition, we measured the growth and ingestion rates
      of other predators at single prey concentrations at which these rates of O.
      marina and G. dominans were saturated. All predators tested in the present study,
      except Balanion sp., preyed on Symbiodinium sp. The specific growth rates of O.
      marina and G. dominans on Symbiodinium sp. increased rapidly with increasing mean
      prey concentration < ca. 740-815 ng C/ml (7,400-8,150 cells/ml), but became
      saturated at higher concentrations. The maximum growth rates of O. marina and G.
      dominans on Symbiodinium sp. (0.87 and 0.61/d) were much higher than those of G.
      moestrupii and P. kofoidii (0.11 and 0.04/d). Symbiodinium sp. did not support
      positive growth of G. spirale, O. rotundata, and Parastrombidinopsis sp. However,
      the maximum ingestion rates of P. kofoidii and Parastrombidinopsis sp. (6.7-10.0
      ng C/predator/d) were much higher than those of O. marina and G. dominans on
      Symbiodinium sp. (1.9-2.1 ng C/predator/d). The results of the present study
      suggest that Symbiodinium sp. may increase or maintain the populations of some
      predators.

PMID- 24102741
TI  - Bond strength of mineral trioxide aggregate to root dentin after exposure to
      different irrigation solutions.
AB  - AIM: The aim of the study was to evaluate the regional push-out bond strength of
      mineral trioxide aggregate (MTA) after exposure to sodium hypochlorite (NaOCl),
      ethylenediaminetetraacetic (EDTA), and peracetic acid (PAA) irrigation solutions.
      MATERIALS AND METHODS: 1-mm-thick longitudinal slabs of root dentin were obtained
      from freshly extracted human canine teeth (n = 80). Simulated root perforation
      defects, 1 mm in diameter, were prepared in the coronal, middle, and apical
      thirds of radicular dentin. Mineral trioxide aggregate was placed into the
      cavities, and the specimens were stored for 1 week at 37 degrees C. Thereafter,
      the specimens were randomly divided into four groups (n = 20) according to the
      irrigation solution applied over the repair sites: Group 1-10 ml of 5.25% NaOCl
      for 10 min; Group 2-10 ml of 5.25% NaOCl for 10 min, followed by 5 ml 17% EDTA
      for 5 min; Group 3-10 ml of 5.25% NaOCl for 10 min, followed by application of 5
      ml 1% PAA for 5 min; and Group 4-no irrigation. Push-out test was performed at a
      crosshead speed of 1 mm/min. Debonding values were compared statistically using
      two-way analysis of variance and Tukey tests (P < 0.05). RESULTS: The push-out
      bond strength of MTA was not affected by the type of irrigation solution or
      location of the perforation defects (both P < 0.05). Stereomicroscopic inspection
      of the samples showed that the bond failure was predominantly adhesive.
      CONCLUSION: Exposure of repaired root perforations to 5.25% NaOCl, 17% EDTA, or
      1% PAA does not alter the dislocation resistance of MTA at different locations of
      root dentin.

PMID- 24102742
TI  - Golgi-mediated glycosylation determines residency of the T2 RNase Rny1p in
      Saccharomyces cerevisiae.
AB  - The role of glycosylation in the function of the T2 family of RNases is not well
      understood. In this work, we examined how glycosylation affects the progression
      of the T2 RNase Rny1p through the secretory pathway in Saccharomyces cerevisiae.
      We found that Rny1p requires entering into the ER first to become active and uses
      the adaptor protein Erv29p for packaging into COPII vesicles and transport to the
      Golgi apparatus. While inside the ER, Rny1p undergoes initial N-linked core
      glycosylation at four sites, N37, N70, N103 and N123. Rny1p transport to the
      Golgi results in the further attachment of high-glycans. Whereas modifications
      with glycans are dispensable for the nucleolytic activity of Rny1p, Golgi
      mediated modifications are critical for its extracellular secretion. Failure of
      Golgi-specific glycosylation appears to direct Rny1p to the vacuole as an
      alternative destination and/or site of terminal degradation. These data reveal a
      previously unknown function of Golgi glycosylation in a T2 RNase as a sorting and
      secretion signal. 

PMID- 24102743
TI  - Perceived support from healthcare professionals, shock anxiety and post-traumatic
      stress in implantable cardioverter defibrillator recipients.
AB  - AIMS AND OBJECTIVES: To investigate (1) the extent to which shock anxiety and
      perceived support from healthcare professionals are related to post-traumatic
      stress disease (PTSD) symptoms and (2) the extent to which perceived support from
      healthcare professionals moderates the relationship between shock anxiety and
      PTSD symptoms in implantable cardioverter defibrillator recipients. An additional
      aim was to describe the level of PTSD symptoms and perceptions of support from
      healthcare professionals. BACKGROUND: Studies examining PTSD symptoms among
      implantable cardioverter defibrillator recipients are still sparse. In addition,
      little is known about how perceived support from healthcare professionals is
      related to PTSD symptoms. DESIGN: Cross-sectional survey design. METHODS:
      Recipients (n = 167) with implantable cardioverter defibrillator attending an
      outpatient device clinic completed questionnaires assessing shock anxiety, PTSD
      symptoms and perceived support from healthcare professionals. RESULTS: The
      results indicated that between ten and 15% of the recipients experienced moderate
      to severe symptoms of PTSD. Although a majority perceived constructive support
      from healthcare professionals, 12% perceived nonconstructive support. Regression
      analysis demonstrated that shock anxiety and perceived nonconstructive support
      from healthcare professionals had a statistically significant (p < 0.01)
      association with PTSD symptoms. Moreover, the results suggest that associations
      between shock anxiety and PTSD symptoms were significantly (p < 0.01) moderated
      by perceived nonconstructive support from healthcare professionals. Young age,
      short time since implantation and secondary prevention indication were also
      significantly associated with PTSD symptoms. CONCLUSIONS: The results indicate
      that nonconstructive support from healthcare professionals can increase the
      tendency to develop PTSD symptoms, particularly in those who experience shock
      anxiety. RELEVANCE TO CLINICAL PRACTICE: Healthcare professionals should pay more
      attention to the way in which they communicate information to the recipients
      during follow-up visits. Clinically based strategies and interventions targeting
      shock anxiety and PTSD symptoms should be carried out.

PMID- 24102744
TI  - Incidence of tracheobronchial anomalies found with hypoplastic left heart
      syndrome.
AB  - BACKGROUND: Tracheobronchial anomalies are rare congenital malformations that are
      typically managed conservatively. Several reports have documented their increased
      incidence in patients with congenital heart disease. However, none of these
      reports have detailed the incidence found among patients with hypoplastic left
      heart syndrome (HLHS). Airway obstruction, whether by extrinsic compression or an
      undiagnosed tracheobronchial anomaly, in the perioperative period may have
      significant morbidity in this tenuous population. METHODS: From June 2003 to
      August 2011, 164 consecutive patients with HLHS underwent a palliative surgical
      procedure for their cardiac disease. Sixty-three of these patients received
      either multidetector computed tomography (CT) of the chest or cardiac magnetic
      resonance imaging (MRI). A total of 124 studies (106 CT, 18 MRI) were performed
      during this time span. The studies were reviewed independently by a pediatric
      cardiologist and a pediatric radiologist. Length of intubation, intensive care
      unit (ICU) stay, and hospital stay were also reviewed for all patients. RESULTS:
      Three of the 63 patients had a congenital abnormality of the tracheobronchial
      tree (4.8%), which is higher than the incidence that has been reported in the
      general population. Two of the patients had bilateral left-sided bronchus with an
      absence of the right upper lobe bronchus. The third patient was found to have a
      very rudimentary right upper lobe bronchus with absence of the right upper lobe
      of the lung. The mean intubation time was not significantly different between the
      groups (P = .615). There was no significant difference of either the total ICU or
      hospital stay between the two groups. CONCLUSION: Our study demonstrates a higher
      incidence of tracheobronchial anomalies among patients with HLHS, a severe form
      of cyanotic congenital heart disease. Patients with a tracheobronchial
      abnormality did not show a difference in morbidity during the postoperative time
      period.

PMID- 24102745
TI  - PD First: peritoneal dialysis as the default transition to dialysis therapy.
AB  - Peritoneal dialysis (PD) and in-center hemodialysis (HD) are accepted as
      clinically equivalent dialysis modalities, yet in-center HD is the predominant
      renal replacement therapy (RRT) modality offered to new end-stage renal disease
      (ESRD) patients in the United States and most other industrialized nations. This
      predominance has little to do with clinical outcomes, patient choice, cost, or
      quality of life. It has been driven by ease of HD initiation, physician
      experience and training, inadequate pre-ESRD patient education, ample in-center
      HD capacity, and lack of adequate infrastructure for PD-related care. As compared
      with in-center HD, PD is a widely applicable, yet underutilized modality of RRT
      that provides comparable clinical outcomes, superior quality of life measures,
      significant cost savings, and many other unmeasured advantages. A "PD First"
      approach not only has advantages for patients but also physicians, healthcare
      systems, and society. In this review, we will summarize evidence demonstrating
      that PD should be the default modality when new ESRD patients are transitioning
      to dialysis therapy when preemptive transplantation is not an option and
      highlight the essential infrastructural requirements to allow for a "PD First"
      model. 

PMID- 24102746
TI  - Progress on obesity prevention over 20 years in Australia and New Zealand.
AB  - The lessons learned from over 20 years of obesity prevention efforts in Australia
      and New Zealand are presented. The obesity epidemic started in the 1980s but poor
      monitoring systems meant the rise in obesity prevalence initially went
      undetected. In the 1990 s, experts started advocating for government action;
      however, it was the rapid increase in media reports on obesity in the early 2000s
      which created the pressure for action. Several, comprehensive reports produced
      some programme investment but no regulatory policies were implemented. The
      powerful food industry lobby ensured this lack of policies on front-of-pack food
      labelling, restrictions on unhealthy food marketing to children, or taxes on
      unhealthy foods. The New Zealand government even backpedalled by rescinding
      healthy school food guidelines and withdrawing funding for the comprehensive
      national obesity strategy. In 2007, Australian Governments started a major long
      term-investment in preventive health in order to improve economic productivity.
      Other positive initiatives, especially in Australia, were: the establishment of
      several advocacy organizations; successful, long-term, whole-of-community
      projects reducing childhood obesity; a national knowledge exchange system for
      practitioners; and some innovative programmes and social marketing. However,
      despite multiple reports and strong advocacy, key recommended regulatory policies
      remain unimplemented, largely due to the private sector interests dominating
      public policy development.

PMID- 24102747
TI  - Hospital utilization in adults with single ventricle congenital heart disease and
      cardiac arrhythmias.
AB  - OBJECTIVES: The study sought to identify the impact of cardiac arrhythmias on
      hospitalizations in adults with single ventricle (SV) congenital heart disease
      (CHD). BACKGROUND: Surgical advances have dramatically improved survival in
      patients with CHD. Cardiac arrhythmias and sudden cardiac death are common in
      adults with CHD. METHODS AND RESULTS: Data from 43 pediatric hospitals in the
      2004 to 2011 Pediatric Health Information System database were used to identify
      patients >=18 years of age admitted with International Classification of Diseases
      9th Revision codes for a diagnosis of either hypoplastic left heart syndrome
      (HLHS), tricuspid atresia (TA) or common ventricle (CV), and a cardiac
      arrhythmia. Primary and secondary diagnoses, length of stay (LOS), hospital
      charges, and interventional procedures were determined. Multilevel models were
      used to evaluate differences in demographics, diagnoses, and clinical outcomes
      among the 3 subgroups (HLHS, TA, and CV). Interactions of charges with arrhythmia
      and admission year were examined using ANOVA. There were 642 admissions in 424
      patients with SV CHD and an arrhythmia diagnosis. A single arrhythmia diagnosis
      was present in 454 admissions (71%). Total hospital charges were $80.7 million
      with mean charge per admission of $127,296 +/- 243,094. The mean charge per
      hospital day was $16,653 +/- 17,516 and increased across the study period (P <
      0.01). Arrhythmia distributions were impacted by SV anatomic subtype (P < 0.001).
      Hospital resource utilization was significantly different among arrhythmia groups
      (P < 0.001). CONCLUSIONS: In adults with SV CHD, arrhythmias are affected by SV
      anatomic subtype and impact adversely upon hospital resource utilization.

PMID- 24102748
TI  - Management of severe asthma in childhood--state of the art and novel
      perspectives.
AB  - The majority of children with asthma have mild or moderate disease and can obtain
      adequate control of symptoms through avoidance of triggering factors and/or with
      the help of medications. There is still a group of children with severe asthma in
      whom symptom control is poor depending either on identifiable aggravating factors
      or on true therapy resistance. These children have a poor quality of life and are
      limited by the severity of their disease. There is a need for a staged approach
      to the assessment and treatment of this small but vulnerable and resource
      consuming group. The current review will provide an overview of a possible
      standardized approach to characterize this heterogeneous group of severely sick
      children including some newly developed ways of assessing asthma severity and
      potentialities of new asthma therapies. Furthermore, the umbrella term
      'problematic severe asthma' is described. The term encompasses children whose
      severe asthma is due to identifiable exacerbating factors, as well as children
      who are resistant to any conventional therapeutic approach. Characteristics of
      these two groups of children are described, as are possible biomarkers and
      current and emerging diagnostic tools for allergy evaluation. Some recent
      advances and future possibilities for treatment of severe asthma are also
      presented in this review. 

PMID- 24102749
TI  - Inactivation of the SecA2 protein export pathway in Listeria monocytogenes
      promotes cell aggregation, impacts biofilm architecture and induces biofilm
      formation in environmental condition.
AB  - Listeria monocytogenes has a dichotomous lifestyle, existing as an ubiquitous
      saprophytic species and as an opportunistic intracellular pathogen. Besides its
      capacity to grow in a wide range of environmental and stressful conditions, L.
      monocytogenes has the ability to adhere to and colonize surfaces. Morphotype
      variation to elongated cells forming rough colonies has been reported for
      different clinical and environmental isolates, including biofilms. This cell
      differentiation is mainly attributed to the reduced secretion of two SecA2
      dependent cell-wall hydrolases, CwhA and MurA. SecA2 is a non-essential SecA
      paralogue forming an alternative translocase with the primary Sec translocon.
      Following investigation at temperatures relevant to its ecological niches, i.e.
      infection (37 degrees C) and environmental (20 degrees C) conditions,
      inactivation of this SecA2-only protein export pathway led, despite reduced
      adhesion, to the formation of filamentous biofilm with aerial structures.
      Compared to the wild type strain, inactivation of the SecA2 pathway promoted
      extensive cell aggregation and sedimentation. At ambient temperature, this effect
      was combined with the abrogation of cell motility resulting in elongated
      sedimented cells, which got knotted and entangled together in the course of
      filamentous-biofilm development. Such a cell differentiation provides a decisive
      advantage for listerial surface colonization under environmental condition. As
      further discussed, this morphotypic conversion has strong implication on
      listerial physiology and is also of potential significance for asymptomatic
      human/animal carriage. 

PMID- 24102750
TI  - Progression of aortic pulse wave velocity in patients with chronic kidney
      disease.
AB  - Aortic pulse wave velocity (aPWV) is elevated in patients with chronic kidney
      disease (CKD) and predicts cardiovascular risk. However, the natural progression
      of arterial stiffness in these patients remains uncertain. Therefore, the main
      aim of this study was to investigate the development of aPWV and to identify
      potential factors associated with its progression. aPWV measurement was carried
      out in 70 CKD patients at baseline and after 12 months. Correlations to several
      variables, in particular annual glomerular filtration rate reduction and diabetes
      mellitus, were studied. In the cohort, aPWV significantly increased in 1 year by
      1.1 m/s (P<.01). Dividing the group into patients with stable and progressive
      aPWV, factors associated with accelerated progression were age, systolic blood
      pressure, and diabetes, whereas loss of renal function had no significant impact.
      The annual aPWV progression in CKD patients reached 1 m/s, which predicts an
      increased cardiovascular risk. Variables involved with progressive arterial
      stiffness need further evaluation. 

PMID- 24102751
TI  - Exploring nursing assistants' roles in the process of pain management for
      cognitively impaired nursing home residents: a qualitative study.
AB  - AIM: To explore nursing assistants' roles during the actual process of pain
      management (assessment, reporting, implementation of pain-relieving interventions
      and re-assessment) for cognitively impaired home residents with pain. BACKGROUND:
      Nursing assistants provide most of the direct care to residents and represent the
      major taskforce in nursing homes. They may develop specialized knowledge of
      residents' pain experience that enables them to play both a pivotal role in pain
      assessment and possibly a supporting role in pain treatment. Currently, there is
      a lack of research into nursing assistants' functions in pain management. DESIGN:
      This is a descriptive, exploratory qualitative study. METHODS: Forty-nine nursing
      assistants were recruited from 12 nursing homes, 12 of them participating in semi
      structured individual interviews and 37 in 8 semi-structured focus groups. All
      interviews were carried out from May to September 2010. Data collected via both
      data collection methods were transcribed verbatim and analysed by content
      analysis. RESULTS: Nursing assistants were found to play four roles in the pain
      management process: (1) pain assessor; (2) reporter; (3) subordinate implementing
      prescribed medications; and (4) instigator implementing non-pharmacological
      interventions. CONCLUSIONS: This study highlights the importance of nursing
      assistants in successful pain assessment and identifies their possible supporting
      roles in other aspects of pain management. However, nursing assistants' scope of
      practice resulted in their functions in pain management being continually
      undervalued by other healthcare professionals. Continuous in-service training,
      the use of a standardized pain management protocol and strategies for building
      coherent work teams in nursing homes are suggested to improve this situation.

PMID- 24102752
TI  - Pirfenidone: a potential new therapy for restrictive allograft syndrome?
AB  - This case report describes the evolution of pulmonary function findings (FVC,
      FEV1 and TLC) and CT features with pirfenidone treatment for restrictive
      allograft syndrome following lung transplantation. Furthermore, we herein report
      hypermetabolic activity on (18) F-FDG PET imaging in this setting, which could
      indicate active fibroproliferation and pleuroparenchymal remodeling. These
      findings may warrant further investigation. 

PMID- 24102753
TI  - Improving nurse faculty retention through a phased retirement process.

PMID- 24102754
TI  - Co-expression of Arabidopsis transcription factor, AtMYB12, and soybean
      isoflavone synthase, GmIFS1, genes in tobacco leads to enhanced biosynthesis of
      isoflavones and flavonols resulting in osteoprotective activity.
AB  - Isoflavones, a group of flavonoids, restricted almost exclusively to family
      Leguminosae are known to exhibit anticancerous and anti-osteoporotic activities
      in animal systems and have been a target for metabolic engineering in commonly
      consumed food crops. Earlier efforts based on the expression of legume isoflavone
      synthase (IFS) genes in nonlegume plant species led to the limited success in
      terms of isoflavone content in transgenic tissue due to the limitation of
      substrate for IFS enzyme. In this work to overcome this limitation, the
      activation of multiple genes of flavonoid pathway using Arabidopsis transcription
      factor AtMYB12 has been carried out. We developed transgenic tobacco lines
      constitutively co-expressing AtMYB12 and GmIFS1 (soybean IFS) genes or
      independently and carried out their phytochemical and molecular analyses. The
      leaves of co-expressing transgenic lines were found to have elevated flavonol
      content along with the accumulation of substantial amount of genistein
      glycoconjugates being at the highest levels that could be engineered in tobacco
      leaves till date. Oestrogen-deficient (ovariectomized, Ovx) mice fed with leaf
      extract from transgenic plant co-expressing AtMYB12 and GmIFS1 but not wild-type
      extract exhibited significant conservation of trabecular microarchitecture,
      reduced osteoclast number and expression of osteoclastogenic genes, higher total
      serum antioxidant levels and increased uterine oestrogenicity compared with Ovx
      mice treated with vehicle (control). The skeletal effect of the transgenic
      extract was comparable to oestrogen-treated Ovx mice. Together, our results
      establish an efficient strategy for successful pathway engineering of isoflavones
      and other flavonoids in crop plants and provide a direct evidence of improved
      osteoprotective effect of transgenic plant extract. 

PMID- 24102755
TI  - Effectiveness of public stroke educational interventions: a review.
AB  - BACKGROUND AND PURPOSE: Recognizing stroke symptoms and acting quickly can reduce
      death and disability, but public awareness of stroke risk factors, symptoms and
      what to do about them is still limited. Stroke educational campaigns are used
      worldwide but there are few published evaluations of such campaigns. METHODS: The
      literature from 1999 to 2012 on the effectiveness of stroke educational campaigns
      was reviewed and summarized with narrative synthesis. Web-based campaigns were
      also described. Three databases and one search engine were explored with two
      keywords (stroke campaign and stroke promotion). The reference lists of all
      included articles were also examined. RESULTS: Twenty-two intervention studies
      and five web-based campaigns were included in the review. Most interventions
      proved partially effective, in terms of gender preference (women) or type of
      information retained or media preferred. Only one intervention proved
      ineffective. Mass media campaigns can be effective but require sustained funding,
      and their ability to target high-risk subgroups, whether aging, linguistic or
      socioeconomic, is unclear. Three community-based participatory stroke promotion
      interventions proved partially effective, but the small sample sizes might have
      underpowered the results. Web-based campaigns are efficient in reaching a large
      number of people but tend to attract a selected and self-selected population.
      CONCLUSIONS: Stroke educational campaigns have the potential to improve knowledge
      and awareness and change the behavior of a large number of people. Health
      promoters and investigators must adopt flexibility and participatory mentality to
      develop cost-effective interventions. Both community-based campaigns and E-tools
      should be integrated within a comprehensive multifaceted stroke promotion
      strategy to expand their reach.

PMID- 24102756
TI  - Placental mesenchymal dysplasia differentially diagnosed from molar pregnancy by
      3-D inversion mode rendering: a case report.
AB  - Placental mesenchymal dysplasia (PMD) is a rare placental vascular anomaly which
      resembles partial molar pregnancy by 2-D ultrasonography. It is challenging but
      clinically important to distinguish between them in order to avoid unnecessary
      termination of pregnancy. A patient was referred to our centre at 13 weeks of
      gestation and 2-D ultrasound of the placenta showed a widespread vesicular
      pattern mixed with normal appearing placenta. Amniotic fluid volume was normal,
      and the fetus appeared to be an appropriate size for gestation without obvious
      structural abnormalities. 3-D reconstruction imaging of the placenta showed a
      large multi-cystic area arising from the chorionic plate which was adjacent to
      normal-appearing placenta. 3-D imaging rendered with 'inversion mode' revealed
      multiple fluid-filled structures with different sizes and appearances. Her serum
      hCG level was slightly elevated. All findings taken together, we suspected PMD
      rather than partial molar pregnancy. Histological examinations of the placenta
      after termination at 15 weeks confirmed the diagnosis. 

PMID- 24102757
TI  - Impact of coffee on liver diseases: a systematic review.
AB  - Coffee is one of the most commonly consumed beverages in the world. Its health
      benefits including improved overall survival have been demonstrated in a variety
      of disease states. To examine the association of coffee consumption with liver
      disease, a systematic review of studies on the effects of coffee on liver
      associated laboratory tests, viral hepatitis, nonalcoholic fatty liver disease
      (NAFLD), cirrhosis and hepatocellular carcinoma (HCC) was performed. Coffee
      consumption was associated with improved serum gamma glutamyltransferase,
      aspartate aminotransferase and alanine aminotransferase values in a dose
      dependent manner in individuals at risk for liver disease. In chronic liver
      disease patients who consume coffee, a decreased risk of progression to
      cirrhosis, a lowered mortality rate in cirrhosis patients, and a lowered rate of
      HCC development were observed. In chronic hepatitis C patients, coffee was
      associated with improved virologic responses to antiviral therapy. Moreover,
      coffee consumption was inversely related to the severity of steatohepatitis in
      patients with non-alcoholic fatty liver disease. Therefore, in patients with
      chronic liver disease, daily coffee consumption should be encouraged. 

PMID- 24102758
TI  - Population pharmacokinetics of ampicillin and sulbactam in patients with
      community-acquired pneumonia: evaluation of the impact of renal impairment.
AB  - AIMS: The aims of this study were to develop a population pharmacokinetic (PK)
      model of ampicillin and sulbactam, to identify patient characteristics
      influencing the PK, and to explore the relationship between dose regimen and
      degree of renal impairment with exposure and time above minimum inhibitory
      concentration (MIC). METHODS: This analysis was performed on PK data for
      ampicillin and sulbactam and MIC data from a clinical trial in Japanese patients
      with community acquired pneumonia. Simulations were performed to investigate the
      effects of different dosing intervals on exposure and time above MIC in various
      degrees of renal impairment. RESULTS: The plasma concentrations from 47 patients
      were adequately described by a two compartment model with simultaneous fit of
      ampicillin and sulbactam PK data, where creatinine clearance on clearance and
      body weight on volume in the peripheral compartment were identified as covariates
      for both drugs. Creatinine clearance contributed to reducing inter-individual
      variability of clearance by 16%. Mean clearance (inter-individual variability)
      for ampicillin and sulbactam was estimated to be 10.7 l h(-1) (14.8%) and 10.4 l
      h(-1) (15.2%), respectively. The time above MIC for each pathogen was generally >
      50% of the treatment period. Simulations for exposure and time above MIC
      supported currently recommended dose adjustments. CONCLUSIONS: This study
      provided a PK model for ampicillin and sulbactam, the time above MICs for
      identified pathogens and associated simulation results. These findings provide
      useful information and augment evidence for the established dosage regimens in
      patients with various degrees of renal impairment.

PMID- 24102759
TI  - Effects of carboxy methyl cellulose and thymol + carvacrol on performance,
      digesta viscosity and some blood metabolites of broilers.
AB  - This study was conducted to evaluate the effects of thymol + carvacrol as plant
      essential oils on performance, digesta viscosity and some blood metabolites of
      broilers fed diets supplemented with carboxy methyl cellulose (CMC) and/or
      thymol+carvacrol. In a completely randomized design with a 2 * 3 factorial
      arrangement, two levels of CMC (0% and 2%) and three levels of thymol+carvacrol
      (0, 100 and 200 mg/kg) were used. Each of the six dietary treatments was fed to
      five replicate pens of 12 birds each from 0 to 42 days of age. Body weight gain
      (BWG), feed intake, feed conversion ratio (FCR), intestinal digesta viscosity and
      pH, plasma lipids and some blood metabolites were recorded. The inclusion of 2%
      CMC decreased (p < 0.05) BWG by 2.2% and increased FCR by 2.3% at 42 days of age.
      Carboxy methyl cellulose significantly increased the digesta viscosity and
      decreased serum total cholesterol, but had no significant effect on triglyceride,
      pH, HDL, LDL and other blood metabolites measured in this experiment.
      Thymol+carvacrol had no effect on feed intake, but significantly increased (p <
      0.05) BWG from 1 to 42 days of age and improved FCR (p < 0.05) by the addition of
      100 and 200 mg/kg thymol+carvacrol respectively. Inclusion of thymol+carvacrol at
      levels of 100 and 200 mg/kg in the diets decreased digesta viscosity and serum
      total cholesterol (p < 0.05) and also increased AST at a 200 mg/kg
      thymol+carvacrol without any effect on creatine kinase (CK). Thymol+carvacrol
      significantly increased total protein (TP), albumin and globulin (p < 0.05). In
      conclusion, CMC at an inclusion level of 2% of diet increased digesta viscosity
      and reduced growth performance. However, thymol+carvacrol decreased digesta
      viscosity and consequently improved the performance of broilers fed the CMC-based
      diet. Therefore, thymol+carvacrol addition to viscose-based diets might be
      helpful to alleviate the negative effects of viscous compounds in poultry diets. 

PMID- 24102760
TI  - Improving accuracy of DNA diet estimates using food tissue control materials and
      an evaluation of proxies for digestion bias.
AB  - Ecologists are increasingly interested in quantifying consumer diets based on
      food DNA in dietary samples and high-throughput sequencing of marker genes. It is
      tempting to assume that food DNA sequence proportions recovered from diet samples
      are representative of consumer's diet proportions, despite the fact that captive
      feeding studies do not support that assumption. Here, we examine the idea of
      sequencing control materials of known composition along with dietary samples in
      order to correct for technical biases introduced during amplicon sequencing and
      biological biases such as variable gene copy number. Using the Ion Torrent
      PGM((c)) , we sequenced prey DNA amplified from scats of captive harbour seals
      (Phoca vitulina) fed a constant diet including three fish species in known
      proportions. Alongside, we sequenced a prey tissue mix matching the seals' diet
      to generate tissue correction factors (TCFs). TCFs improved the diet estimates
      (based on sequence proportions) for all species and reduced the average estimate
      error from 28 +/- 15% (uncorrected) to 14 +/- 9% (TCF-corrected). The
      experimental design also allowed us to infer the magnitude of prey-specific
      digestion biases and calculate digestion correction factors (DCFs). The DCFs were
      compared with possible proxies for differential digestion (e.g. fish protein%,
      fish lipid%) revealing a strong relationship between the DCFs and percent lipid
      of the fish prey, suggesting prey-specific corrections based on lipid content
      would produce accurate diet estimates in this study system. These findings
      demonstrate the value of parallel sequencing of food tissue mixtures in diet
      studies and offer new directions for future research in quantitative DNA diet
      analysis.

PMID- 24102761
TI  - Fluoride-sensitivity of growth and acid production of oral Actinomyces:
      comparison with oral Streptococcus.
AB  - Actinomyces are predominant oral bacteria; however, their cariogenic potential in
      terms of acid production and fluoride sensitivity has not been elucidated in
      detail and compared with that of other caries-associated oral bacteria, such as
      Streptococcus. Therefore, this study aimed to elucidate and compare the acid
      production and growth of Actinomyces and Streptococcus in the presence of
      bicarbonate and fluoride to mimic conditions in the oral cavity. Acid production
      from glucose was measured by pH-stat at pH 5.5 and 7.0 under anaerobic
      conditions. Growth rate was assessed by optical density in anaerobic culture.
      Although Actinomyces produced acid at a lower rate than did Streptococcus, their
      acid production was more tolerant of fluoride (IDacid production 50 = 110-170 ppm
      at pH 7.0 and 10-13 ppm at pH 5.5) than that of Streptococcus (IDacid production
      50 = 36-53 ppm at pH 7.0 and 6.3-6.5 ppm at pH 5.5). Bicarbonate increased acid
      production by Actinomyces with prominent succinate production and enhanced their
      fluoride tolerance (IDacid production 50 = 220-320 ppm at pH 7.0 and 33-52 ppm at
      pH 5.5). Bicarbonate had no effect on these variables in Streptococcus. In
      addition, although the growth rate of Actinomyces was lower than that of
      Streptococcus, Actinomyces growth was more tolerant of fluoride (IDgrowth 50 =
      130-160 ppm) than was that of Streptococcus (IDgrowth 50 = 27-36 ppm). These
      results indicate that oral Actinomyces are more tolerant of fluoride than oral
      Streptococcus, and bicarbonate enhances the fluoride tolerance of oral
      Actinomyces. Because of the limited number of species tested here, further study
      is needed to generalize these findings to the genus level. 

PMID- 24102762
TI  - Bellagio Declaration 2013: countering Big Food's undermining of healthy food
      policies.

PMID- 24102763
TI  - Cognitive performance in pediatric liver transplant recipients.
AB  - To date, the course of cognitive development in children after liver
      transplantation (Ltx) is poorly understood. Cognitive performance, however, is
      crucial in all developmental stages and for educational achievement. This cross
      sectional single-center study examined the prevalence of long-term cognitive
      impairment in a cohort of 64 pediatric patients after Ltx. Median age at Ltx was
      12 months. The revised Wechsler Intelligence Scale IV was administered to assess
      cognitive performance. Patients were compared with an age- and gender-matched
      group of children without a chronic health condition. Liver transplanted children
      performed significantly worse in three of four cognitive domains as well as in
      the Total Intelligence Quotient (Total IQ) (p = 0.017 to p = 0.005). Liver
      transplant recipients showed substantially more "serious delays" (IQ < 70)
      compared to the reference group (9.4% vs. 4.7%). Children with a genetic
      metabolic disease performed worse than the other groups in three of the four WISC
      Indices and in the Total IQ (p = 0.05 to p = 0.01). The strongest association was
      revealed between height at Ltx and Verbal Comprehension (R(2)  = 0.21),
      Perceptual Reasoning (R(2)  = 0.30), Working Memory (R(2)  = 0.23) and Total IQ
      (R(2)  = 0.25). Our results indicate a high impact of primary diagnosis and
      height percentile at Ltx even on children's long-term cognitive performance. 

PMID- 24102764
TI  - Ribosomal gene polymorphism in small genomes: analysis of different 16S rRNA
      sequences expressed in the honeybee parasite Nosema ceranae (Microsporidia).
AB  - To date, few organisms have been shown to possess variable ribosomal RNA,
      otherwise considered a classic example of uniformity by concerted evolution. The
      polymorphism for the 16S rRNA in Nosema ceranae analysed here is striking as
      Microsporidia are intracellular parasites which have suffered a strong reduction
      in their genomes and cellular organization. Moreover, N. ceranae infects the
      honeybee Apis mellifera, and has been associated with the colony-loss phenomenon
      during the last decade. The variants of 16S rRNA include single nucleotide
      substitutions, one base insertion-deletion, plus a tetranucleotide indel. We show
      that different gene variants are expressed. The polymorphic sites tend to be
      located in particular regions of the rRNA molecule, and the comparison to the
      Escherichia coli 16S rRNA secondary structure indicates that most variations
      probably do not preclude ribosomal activity. The fact that the polymorphisms in
      such a minimal organism as N. ceranae are maintained in samples collected
      worldwide suggest that the existence of differently expressed rRNA may play an
      adaptive role in the microsporidian. 

PMID- 24102765
TI  - Artificial dermis (Matriderm(r)) followed by skin graft as an option in
      dermatofibrosarcoma protuberans with complete circumferential and peripheral deep
      margin assessment.
AB  - Dermatofibrosarcoma protuberans (DFSP) is a locally invasive neoplasia with a
      pattern of infiltrative growth that leads to extended resections. To avoid
      unnecessary resections and spare tissues, its treatment requires an adequate
      assessment of the margins. We present a case where artificial dermis
      (Matriderm(r)) was used followed by skin graft for reconstruction. We present a
      50-year-old woman with a DFSP in the occipital region. She was referred to us
      after a first surgery with positive margins. A wide local excision with a 2-cm
      margin was performed and periosteal tissue was also removed, which led to
      exposure of the skull. Matriderm was placed on the bone surface and dressings
      were changed every other day. Meanwhile, margins were evaluated by the complete
      circumferential and peripheral deep margin assessment (CCPDMA) and were positive
      for DFSP in the superior margin. After 4 weeks the area was completely covered by
      granulation tissue and a new resection followed by reconstruction with a skin
      graft was performed. With regard to the difficulties in the margin assessment in
      DFSP, we present artificial dermis (Matriderm) as an option for reconstructive
      surgery in these patients, especially when a skin graft cannot be performed as a
      first option. 

PMID- 24102766
TI  - Nanosafety: towards safer design of nanomedicines.

PMID- 24102767
TI  - Exposure to ertapenem is possibly associated with Pseudomonas aeruginosa
      antibiotic resistance.
AB  - The role of antibiotic exposure in the evolution and emergence of resistance is
      challenging to assess. We used carbapenem-resistant Pseudomonas aeruginosa (PA)
      phenotypes to assess possible factors that are associated with the occurrence and
      prognosis of such a phenotype and to examine the possible contribution of
      antibiotic exposure to the evolution of antimicrobial resistance. We conducted a
      nested case-control study. Cases were defined as patients from whom carbapenem
      resistant ureidopenicillin-sensitive PA (CRUS-PA) was isolated; matched controls
      were PA patients who did not have isolation of CRUS-PA. We analysed potential
      predictors of CRUS-PA isolation and assessed their clinical significance
      (mortality and eventual isolation of pan-resistant PA), taking into account
      antibiotic exposures. We matched 800 case-control pairs. Case patients were more
      likely to have been exposed to anti-PA carbapenems (OR = 6.9; 95% CI, 2.5-18.6).
      This finding did not apply to the administration of other antibiotics. The
      mortality among CRUS-PA patients was similar to that of the controls (HR, 0.8
      95%; CI, 0.6-1.1). Subsequent isolation of pan-resistant PA was more frequent
      among case patients compared with non-pan-resistant controls (p-value <0.05).
      Among cases, the risk of eventual pan-resistant PA isolation was increased in
      ertapenem recipients, only after and not prior to the index specimen date (HR,
      1.9, 95%; CI, 1.01-3.4). Therefore we suggest that the CRUS-PA phenotype may
      represent pan beta-lactam resistance and that antibiotic exposure is associated
      with evolution of PA resistance phenotypes. We demonstrate a novel association of
      ertapenem with sequentially appearing PA resistance patterns.

PMID- 24102768
TI  - Diagnosis and treatment of resistant hypertension: the critical role of
      ambulatory blood pressure monitoring.

PMID- 24102769
TI  - Simple and direct assembly of kymographs from movies using KYMOMAKER.
AB  - In tracking analysis, the movement of cargos by motor proteins in axons is often
      represented by a time-space plot termed a 'kymograph'. Manual creation of
      kymographs is time-consuming and complicated for cell biologists. Therefore, we
      developed KYMOMAKER, a simple system that automatically creates a kymograph from
      a movie without generating multiple time-dissected movie stacks. In addition,
      KYMOMAKER can automatically extract faint vesicle traces, and can thereby
      effectively analyze cargos expressed at low levels in axons. A filter can be
      applied to remove traces of non-physiological movements and to extract meaningful
      traces of anterograde or retrograde cargo transport. For example, only cargos
      that move at a speed of >0.4 um/second for a distance of >1 um can be included.
      Another function of KYMOMAKER is to create a color kymograph in which the color
      of the trace varies according to the position of the fluorescent particle in the
      axis perpendicular to the long axis of the axon. Such positional information is
      completely lost in conventional kymographs. KYMOMAKER is an open access program
      that can be easily used to analyze vesicle transport in axons by cell biologists
      who do not have specific knowledge of bioimage informatics. 

PMID- 24102771
TI  - The significance of transesophageal echocardiography in assessing congenital
      heart disease: our experience.
AB  - BACKGROUND: The rapid expansion of pediatric cardiovascular surgery, along with
      the increase in the number of centers and operations, has also increased the use
      of intraoperative transesophageal echocardiography (TEE). Preoperative TEE allows
      for the confirmation of diagnoses established by transthoracic echocardiography
      and angiography, and also identifies possible additional pathologic conditions.
      TEE is also used to follow up on surgical repairs, determine the need for
      reintervention, and evaluate myocardial performance and the need for inotropic
      treatment. Our intention is to share the TEE findings before and after
      intervention for congenital heart disease in patients who received operations at
      our center, and the conclusions reached. PATIENTS AND METHOD: From October 2009
      to February 2013, 1008 patients underwent surgery for congenital heart disease.
      Of these, 265 were subjected to TEE in the operating room. Each patient entering
      the operating room with TEE planned had the echocardiography probe placed while
      intubated under general anesthesia. TEE studies used a GE Vivid S5. Different
      investigations, according to the patients' particular pathologic conditions, were
      also performed in addition to standard TEE studies. RESULTS: Of the 265 patients
      for whom surgery was indicated by transthoracic echocardiography and other
      appropriate examinations, 260 had the diagnosis confirmed by preoperative TEE and
      the indicated intervention was performed. For the remaining 5 patients (1.8%),
      the intervention plan was changed following preoperative TEE. Cardiopulmonary
      bypass was reinitiated in 12 (4.5%) patients because of residual defects
      identified by postoperative TEE. Thus, the preoperative plan was changed in 17
      (6.4%) patients out of a total of 265 owing to preoperative and postoperative TEE
      findings. CONCLUSION: The use of intraoperative TEE in surgical centers for
      congenital heart disease allows for a significant reduction in mortality and
      morbidity. Intraoperative TEE performed by experienced pediatric cardiologists is
      therefore an absolute necessity.

PMID- 24102770
TI  - Controversies in timing of dialysis initiation and the role of race and
      demographics.
AB  - Dialysis remains the predominant form of renal replacement therapy in the United
      States, but the optimal timing for the initiation of dialysis remains poorly
      defined. Not only clinical factors such as signs/symptoms of uremia, co-existing
      cardiovascular disease, and presence of diabetes but also key demographic
      characteristics including age, gender, race/ethnicity, and socioeconomics have
      all been considered as potential modifying factors in the decision for the timing
      of dialysis initiation. The 2012 Kidney Disease: Improving Global Outcomes
      (KDIGO) Clinical Practice Guideline for the Evaluation and Management of chronic
      kidney disease (CKD) suggests that dialysis be initiated when signs/symptoms
      attributable to kidney failure such as serositis, acid-base or electrolyte
      abnormalities, pruritus, poorly controlled volume status or blood pressure,
      deteriorating nutritional status despite dietary intervention, or cognitive
      impairment are visible or noted. These signs/symptoms typically occur when the
      glomerular filtration rate (GFR) is in the range of 5-10 ml/minute/1.73 m(2) ,
      although they may occur at higher levels of GFR. We review recent data on the
      timing of dialysis initiation, their implications for managing patients with late
      stage CKD, and the important role of considering key demographics in making
      patient-centered decisions for the timing of dialysis initiation.

PMID- 24102772
TI  - Suicide attempt by complete self-removal of a 12-year-old permanent pacemaker
      system: case report.
AB  - INTRODUCTION: Psychological adaption after pacemaker implantation can be
      challenging in patients with psychiatric disease. Suicide by self-removal of a
      permanent pacemaker system is a rare phenomenon described in a few cases in
      patients with psychiatric disorders. METHODS AND RESULTS: We describe a case of
      attempted suicide by complete self-removal of a 12-year-old permanent pacemaker
      system in a 70-year-old male patient with a bipolar disorder and a history of
      previous suicide attempts. CONCLUSIONS: Suicide attempt by self-removal of a
      permanent pacemaker system is very rare. In patients with a history of
      psychiatric disease and previous suicide attempts, careful information about the
      function of a pacemaker should be given.

PMID- 24102773
TI  - A prospective study analyzing one-year multidimensional outcomes in living lung
      transplant donors.
AB  - The success of living-donor lobar lung transplantation (LDLLT) largely depends on
      donor outcome; but to date, no authors have studied health-related quality of
      life (HRQOL) of donors. We prospectively evaluated multidimensional outcomes
      before and 1 year after donor lobectomies. Patient-reported HRQOL, dyspnea,
      psychological status and sleep quality, and physiological pulmonary function were
      determined. All donors were alive without any limitations in their activities of
      daily living after 1 year. Postoperative pulmonary function was better than the
      estimated preoperative values; but, with respect to HRQOL, four of the eight
      subscales of the Medical Outcomes Study 36-item short form (SF-36) deteriorated
      significantly after donation. In addition, dyspnea assessed by the modified
      Medical Research Council scale also worsened significantly. In contrast,
      postoperative anxiety assessed by the Hospital Anxiety and Depression Scale
      significantly improved from baseline. The donors whose recipients died reported
      lower SF-36 scores with worsening sleep quality measured by Pittsburgh Sleep
      Quality Index. Thus, although postoperative pulmonary functions in donors were
      preserved, their HRQOL and dyspnea deteriorated postoperatively. Moreover, HRQOL
      and sleep quality were impaired in recipients who experienced poor outcomes. To
      capture the comprehensive outcomes in LDLLT donors after donation, patient
      reported outcomes should be analyzed separately from physiological outcomes. 

PMID- 24102774
TI  - A qualitative study of regional anaesthesia for vitreo-retinal surgery.
AB  - AIM: The aim of this research was to collect experiential knowledge about
      regional ocular anaesthesia - an integral component of most vitreo-retinal
      surgery. BACKGROUND: Anaesthesia for vitreo-retinal surgery has predominantly
      used general anaesthesia, because of the length and complexity of the surgical
      procedure. However, recent advances in surgical instrumentation and techniques
      have reduced surgical times; this decision has led to the adoption of regional
      ocular anaesthesia for vitreo-retinal day surgery. Although regional ocular
      anaesthesia has been studied from several perspectives, knowledge about patients'
      experience of the procedure is limited. DESIGN: An interpretive qualitative
      research methodology underpinned by Gadamer's philosophical hermeneutics.
      METHODS: Eighteen participants were interviewed in-depth between July 2006
      December 2007 following regional ocular anaesthesia. Interview data were
      thematically analysed by coding and grouping concepts. FINDINGS: Four themes were
      identified: 'not knowing': the time prior to the experience of a regional eye
      block; 'experiencing': the experience of regional ocular anaesthesia; 'enduring':
      the capacity participants displayed to endure regional ocular anaesthesia with
      the hope that their vision would be restored; and 'knowing': when further surgery
      was required and past experiences were recalled. CONCLUSIONS: The experience of
      regional ocular anaesthesia had the capacity to invoke anxiety in the
      participants in this study. Many found the experience overwhelming and painful.
      What became clear was the participant's capacity to stoically 'endure' regional
      ocular anaesthesia, indicating the value people placed on visual function.

PMID- 24102775
TI  - The production of recombinant cationic alpha-helical antimicrobial peptides in
      plant cells induces the formation of protein bodies derived from the endoplasmic
      reticulum.
AB  - Synthetic linear antimicrobial peptides with cationic alpha-helical structures,
      such as BP100, are valuable as novel therapeutics and preservatives. However,
      they tend to be toxic when expressed at high levels as recombinant peptides in
      plants, and they can be difficult to detect and isolate from complex plant
      tissues because they are strongly cationic and display low extinction coefficient
      and extremely limited immunogenicity. We therefore expressed BP100 with a C
      terminal tag which preserved its antimicrobial activity and demonstrated
      significant accumulation in plant cells. We used a fluorescent tag to trace BP100
      following transiently expression in Nicotiana benthamiana leaves and showed that
      it accumulated in large vesicles derived from the endoplasmic reticulum (ER)
      along with typical ER luminal proteins. Interestingly, the formation of these
      vesicles was induced by BP100. Similar vesicles formed in stably transformed
      Arabidopsis thaliana seedlings, but the recombinant peptide was toxic to the host
      during latter developmental stages. This was avoided by selecting active BP100
      derivatives based on their low haemolytic activity even though the selected
      peptides remained toxic to plant cells when applied exogenously at high doses.
      Using this strategy, we generated transgenic rice lines producing active BP100
      derivatives with a yield of up to 0.5% total soluble protein. 

PMID- 24102777
TI  - Change of childbirth preference after delivery among nulliparous Chinese women
      and their partners.
AB  - AIM: The aim of the present study was to assess the effect of childbirth
      preference among nulliparous Chinese women and their partners on actual mode of
      delivery, and to assess women's change in preference from vaginal delivery to
      cesarean and the factors associated with this change. METHODS: A cohort study was
      conducted from July to October 2011 in the First Hospital of Tsinghua University,
      Beijing. Nulliparous women at the gestational age of 36-40 weeks and their
      partners were included. Their childbirth preference was recorded twice: once in
      pregnancy and again 2 or 3 days post-partum. RESULTS: Women preferring cesarean
      during pregnancy had a 3.9-fold higher chance of undergoing a cesarean than those
      preferring vaginal delivery (P = 0.004), while the partner's preference had no
      effect (P = 0.35). Preference for cesarean in the post-partum period increased
      significantly compared to that during pregnancy both among women, whose
      preference increased from 10.1% to 28.0%, and among their partners, whose
      preference increased from 7.8% to 16.7% (P < 0.001 for both). The rate of change
      in women's preference from vaginal delivery to cesarean was 26.0%. Women having
      high couple's monthly income, who were feeling depressed, whose partner preferred
      cesarean during pregnancy or who delivered by cesarean were more likely to
      experience this change due to fear of labor pain and perineal cutting and a
      greater perceived safety of cesarean. CONCLUSION: Women's cesarean preference
      during pregnancy was associated with actual cesarean delivery. Inadequate quality
      of care in labor and delivery and overestimation of cesarean safety underlie post
      partum women's increased preference for cesarean.

PMID- 24102776
TI  - Seasonally variable intestinal metagenomes of the red palm weevil (Rhynchophorus
      ferrugineus).
AB  - The intestinal microbes residing in the red palm weevil (RPW, Rhynchophorus
      ferrugineus) larva consume tender interior fibrous tissues of date palm trunks.
      The understanding of such microbiota at molecular level provides vital clues for
      the biological control of this devastating pest. Using pyrosequencing and shotgun
      strategy, we first study taxonomic profiles of the microbiota sampled at
      different months (March, July and November), and then confirm the impact of high
      temperature stress on the microbial populations based on data from 16S rRNA
      amplicons using both field and laboratory samples. We further identify Klebsiella
      pneumoniae in November and Lactococcus lactis in July as the dominant species of
      the microbiota. We find that the RPW gut microbiota degrades polysaccharides and
      sucrose with hydrolases and that different active bacterial species in November
      and July are responsible for the symbiotic relationship between the microbiota
      and the host. Our results provide vital information for pest control and
      cellulolytic bacterial species characterization. 

PMID- 24102778
TI  - Prevalence and epidemiological characteristics of vaginal candidiasis in the UAE.
AB  - Vaginal candidiasis (VC) continues to be a health problem to women worldwide.
      Although the majority of VC cases are caused by Candida albicans (C. albicans),
      non-albicans Candida spp. like C. glabrata and C. tropicalis are emerging as
      important and potentially resistant opportunistic agents of VC. The objective of
      this study was to evaluate the prevalence and epidemiology of VC in the UAE
      through retrospective analysis of pertinent data compiled by the microbiology and
      infection control unit at Latifa Hospital, Dubai between 2005 and 2011. The
      incidence of VC significantly increased from 10.76% in 2005 to 17.61% in 2011;
      average prevalence was 13.88%. C. albicans occurred at a frequency of 83.02%, C.
      glabrata at 16.5% and C. tropicalis at 1.2%. A single C. dubliniensis isolate was
      identified in the sample population. The percentage of C. albicans significantly
      decreased from 83.02% in the sample population as a whole to 60.8% in subjects
      over 45 years of age (P < 0.01) and that of C. glabrata, C. tropicalis and C.
      krusei significantly increased from 13.88%, 0.9% and 0.03% to 29.7%, 6.7% and
      1.4% (P < 0.05) respectively. The incidence of VC in the UAE is on the rise and
      the frequency of non-albicans Candida spp. is noticeably increasing especially in
      postmenopausal women. 

PMID- 24102779
TI  - Soluble immunoglobulin A in breast milk is inversely associated with atopic
      dermatitis at early age: the PASTURE cohort study.
AB  - BACKGROUND: The role of breastfeeding for the development of atopic diseases in
      childhood is contradictory. This might be due to differences in the composition
      of breast milk and levels of antimicrobial and anti-inflammatory components.
      OBJECTIVE: The objective of this study was to examine whether levels of total
      immunoglobulin A (IgA) or transforming growth factor-beta1 (TGF-beta1) in breast
      milk were associated with the risk of developing atopic dermatitis (AD), atopic
      sensitization or asthma at early age taking breastfeeding duration into account.
      METHODS: The birth cohort study PASTURE conducted in Finland, France, Germany and
      Switzerland provided 610 breast milk samples collected 2 months after delivery in
      which soluble IgA (sIgA) and TGF-beta1 levels were measured by ELISA. Duration of
      breastfeeding was assessed using weekly food frequency diaries from month 3 to
      month 12. Data on environmental factors, AD and asthma were collected by
      questionnaires from pregnancy up to age 6. Atopic status was defined by specific
      IgE levels in blood collected at the ages of 4 and 6 years. Multivariate logistic
      regression models were used for statistical analysis. RESULTS: Soluble IgA and
      TGF-beta1 levels in breast milk differed between countries, and sIgA levels were
      associated with environmental factors related to microbial load, for example,
      contact to farm animals or cats during pregnancy, but not with raw milk
      consumption. sIgA levels were inversely associated with AD up to the of age 2
      years (P-value for adjusted linear trend: 0.005), independent of breastfeeding
      duration. The dose of sIgA ingested in the first year of life was associated with
      reduced risk of AD up to the age of 2 (aOR, 95% CI: 0.74; 0.55-0.99) and 4 years
      (0.73; 0.55-0.96). No clear associations between sIgA and atopy or asthma up to
      age 6 were observed. TGF-beta1 showed no consistent association with any
      investigated health outcome. CONCLUSION AND CLINICAL RELEVANCE: IgA in breast
      milk might protect against the development of AD.

PMID- 24102780
TI  - Summer meeting 201--when the sleepers wake: the germination of spores of Bacillus
      species.

PMID- 24102782
TI  - Pressure ulcer stage IV caused by cervical collar in patients with multiple
      trauma in intensive care unit.

PMID- 24102781
TI  - Programme and policy options for preventing obesity in China.
AB  - By 2002, China's prevalence of overweight and obesity among adults was 18.9 and
      2.9%, respectively. The replacement of traditional Chinese diet with 'Western
      diet', major declines in all phases of activity and increased sedentary activity
      are cited as the main reasons explaining the rapid increase in overweight and
      obesity, which bring major economic and health costs. The Nutrition Improvement
      Work Management Approach was released in 2010. Overweight and obesity prevention
      related policies were added to national planning for disease prevention and
      control. The Guidelines for Prevention and Control of Overweight and Obesity of
      Chinese Adults and the School-age Children and Teenagers Overweight and Obesity
      Prevention and Control Guidelines in China were promulgated in 2003 and 2007,
      respectively. Few education programmes have been implemented. Selected academic
      intervention research projects dominate with a focus on reducing child obesity
      and promoting healthier diets; increasing physical activity and reducing
      sedentary time; and facilitating changes in family, school, social and cultural
      environments. Intervention samples are small and have not addressed the
      increasing rates of obesity throughout the entire population. Government
      provision of effective policy measures, multisectoral cooperation and increasing
      corporate social responsibility are keys to curbing the trend towards overweight
      and obesity in China. 

PMID- 24102783
TI  - Comparison of stool antigen immunoassay and serology for screening for
      Helicobacter pylori infection in intellectually disabled children.
AB  - Diagnosis of active Helicobacter pylori infection in intellectually disabled (ID)
      children is problematic because they are unable to cooperate with performance of
      invasive tests. In this study, the non-invasive methods of measuring serum IgG
      antibody concentrations and performing stool antigen tests were used to screen
      for H. pylori infection in ID children. Eighty-seven children with intellectual
      disabilities were studied. The amount of serum IgG antibody against H. pylori was
      measured by the ELISA method. Stool samples were examined using an amplified
      IDEIA HpStAR kit. To assess categorical variables, X(2) , Fisher's exact and
      Kappa tests were used. The stool antigen tests showed that 93.1% of the children
      had H. pylori antigen and the serology test that 85.1% of children were positive
      for H. pylori IgG antibodies. Agreement between results of H. pylori stool
      antigen (HpSA) testing and IgG antibody serology was 82.8%; however, according to
      the kappa measure of agreement this agreement is not statistically significant
      (value, 0.128; P = 0.19). Discordant results were observed for 15 children
      (17.2%): 11 (12.6%) who were positive on HpSA test but negative by serology and 4
      (4.6%) who were IgG seropositive but had negative HpSA tests. This study showed a
      notably higher rate of H. pylori infection in ID children than has been reported
      by others for non-ID children from the same geographical area. The HpSA test is a
      valid method for primary screening for H. pylori infection in ID children; it
      detects the specific antigens shed during active infections and has less cross
      reactivity than serological tests that detect antibodies. HpSA is a sensitive non
      invasive method for detecting infection in ID children and may serve as an
      accurate alternative to serology. 

PMID- 24102784
TI  - On the accumulation of deleterious mutations during range expansions.
AB  - We investigate the effect of spatial range expansions on the evolution of fitness
      when beneficial and deleterious mutations cosegregate. We perform individual
      based simulations of 1D and 2D range expansions and complement them with
      analytical approximations for the evolution of mean fitness at the edge of the
      expansion. We find that deleterious mutations accumulate steadily on the wave
      front during range expansions, thus creating an expansion load. Reduced fitness
      due to the expansion load is not restricted to the wave front, but occurs over a
      large proportion of newly colonized habitats. The expansion load can persist and
      represent a major fraction of the total mutation load for thousands of
      generations after the expansion. The phenomenon of expansion load may explain
      growing evidence that populations that have recently expanded, including humans,
      show an excess of deleterious mutations. To test the predictions of our model, we
      analyse functional genetic diversity in humans and find patterns that are
      consistent with our model. 

PMID- 24102785
TI  - ESCMID and ECMM joint clinical guidelines for the diagnosis and management of
      rare invasive yeast infections.
AB  - The mortality associated with invasive fungal infections remains high with that
      involving rare yeast pathogens other than Candida being no exception. This is in
      part due to the severe underlying conditions typically predisposing patients to
      these healthcare-related infections (most often severe neutropenia in patients
      with haematological malignancies), and in part due to the often challenging
      intrinsic susceptibility pattern of the pathogens that potentially leads to
      delayed appropriate antifungal treatment. A panel of experts of the European
      Society of Clinical Microbiology and Infectious Diseases (ESCMID) Fungal
      Infection Study Group (EFISG) and the European Confederation of Medical Mycology
      (ECMM) undertook a data review and compiled guidelines for the diagnostic tests
      and procedures for detection and management of rare invasive yeast infections.
      The rare yeast pathogens were defined and limited to the following
      genera/species: Cryptococcus adeliensis, Cryptococcus albidus, Cryptococcus
      curvatus, Cryptococcus flavescens, Cryptococcus laurentii and Cryptococcus
      uniguttulatus (often published under the name Filobasidium uniguttulatum),
      Malassezia furfur, Malassezia globosa, Malassezia pachydermatis and Malassezia
      restricta, Pseudozyma spp., Rhodotorula glutinis, Rhodotorula minuta and
      Rhodotorula mucilaginosa, Sporobolomyces spp., Trichosporon asahii, Trichosporon
      asteroides, Trichosporon dermatis, Trichosporon inkin, Trichosporon jirovecii,
      Trichosporon loubieri, Trichosporon mucoides and Trichosporon mycotoxinivorans
      and ascomycetous ones: Geotrichum candidum, Kodamaea ohmeri, Saccharomyces
      cerevisiae (incl. S. boulardii) and Saprochaete capitatae (Magnusiomyces
      (Blastoschizomyces) capitatus formerly named Trichosporon capitatum or Geotrichum
      (Dipodascus) capitatum) and Saprochaete clavata. Recommendations about the
      microbiological investigation and detection of invasive infection were made and
      current knowledge on the most appropriate antifungal and supportive treatment was
      reviewed. In addition, remarks about antifungal susceptibility testing were made.

PMID- 24102786
TI  - PNPLA3 I148M (rs738409) genetic variant and age at onset of at-risk alcohol
      consumption are independent risk factors for alcoholic cirrhosis.
AB  - BACKGROUND & AIMS: Environmental and genetic factors contribute to alcoholic
      cirrhosis onset. In particular, age at exposure to liver stressors has been shown
      to be important in progression to fibrosis in hepatitis C individuals. However,
      no definite data on the role of age at onset of at-risk alcohol consumption are
      available. Moreover, patatin-like phospholipase domain-containing protein 3
      (PNPLA3) I148M (rs738409) variant has been associated with alcoholic cirrhosis,
      but only in cross-sectional studies. The aim of this study was to investigate the
      role of age at onset of at-risk alcohol consumption and PNPLA3 I148M variant on
      alcoholic cirrhosis incidence. METHODS: A total of 384 at-risk alcohol drinkers
      were retrospectively examined. The association among age at onset of at-risk
      alcohol consumption, PNPLA3 I148M variant and cirrhosis incidence was tested.
      RESULTS: A higher incidence of alcoholic cirrhosis was observed in individuals
      with an older (>=24 years) compared with a younger (<24) age at onset of at-risk
      alcohol consumption (P-value < 0.001). Moreover, PNPLA3 148M allele carriers
      showed an increased incidence of cirrhosis (P-value < 0.001). Both age at onset
      of at-risk alcohol consumption and PNPLA3 148M allele were independent risk
      factors for developing cirrhosis (H.R. (95% C.I.): 2.76 (2.18-3.50), P-value <
      0.001; 1.53(1.07-2.19), P-value = 0.021 respectively). The 148M allele was
      associated with a two-fold increased risk of cirrhosis in individuals with a
      younger compared with an older age at onset of at-risk alcohol consumption (H.R.
      (95% C.I.): 3.03(1.53-6.00) vs. 1.61(1.09-2.38). CONCLUSIONS: Age at onset of at
      risk alcohol consumption and PNPLA3 I148M genetic variant are independently
      associated with alcoholic cirrhosis incidence.

PMID- 24102787
TI  - Dissecting functions of the conserved oligomeric Golgi tethering complex using a
      cell-free assay.
AB  - Vesicle transport sorts proteins between compartments and is thereby responsible
      for generating the non-uniform protein distribution along the eukaryotic
      secretory and endocytic pathways. The mechanistic details of specific vesicle
      targeting are not yet well characterized at the molecular level. We have
      developed a cell-free assay that reconstitutes vesicle targeting utilizing the
      recycling of resident enzymes within the Golgi apparatus. The assay has
      physiological properties, and could be used to show that the two lobes of the
      conserved oligomeric Golgi tethering complex play antagonistic roles in trans
      Golgi vesicle targeting. Moreover, we can show that the assay is sensitive to
      several different congenital defects that disrupt Golgi function and therefore
      cause glycosylation disorders. Consequently, this assay will allow mechanistic
      insight into the targeting step of vesicle transport at the Golgi, and could also
      be useful for characterizing some novel cases of congenital glycosylation
      disorders. 

PMID- 24102788
TI  - Angiotensin II regulates islet microcirculation and insulin secretion in mice.
AB  - OBJECTIVE: Angiotensin II causes potent increases in systemic and local pressure
      through its vasoconstrictive effect. Despite the importance of angiotensin II for
      local blood flow regulation, whether angiotensin II regulates the pancreatic
      islet microcirculation remains incompletely understood. We hypothesized that
      angiotensin II directly regulates the pancreatic islet microcirculation and
      thereby regulates insulin secretion. The aims of this study were to develop a new
      technique to visualize pancreatic islet hemodynamic changes in vivo and to
      analyze changes in islet circulation induced by angiotensin II or an angiotensin
      type 1 receptor blocker. METHODS: Using an in vivo imaging method, we observed
      the pancreatic islet microcirculation. Various doses of angiotensin II or an
      angiotensin type 1 receptor blocker were injected intravenously, and changes in
      islet microcirculation were observed. Glucose-stimulated insulin secretion from
      the pancreas was measured from the hepatic portal vein. RESULTS: We identified
      islet microcirculation using a fluorescent dye. Angiotensin II significantly
      induced blood vessel contraction in the islets in a dose-dependent manner. In
      contrast, the angiotensin type 1 receptor blocker induced vasodilation. Glucose
      stimulated insulin secretion was decreased by angiotensin II infusion.
      CONCLUSIONS: These results show that angiotensin II is involved in the regulation
      of pancreatic islet microcirculation and insulin secretion.

PMID- 24102789
TI  - More than a diagnosis.

PMID- 24102790
TI  - CD40-independent help by memory CD4 T cells induces pathogenic alloantibody but
      does not lead to long-lasting humoral immunity.
AB  - CD40/CD154 interactions are essential for productive antibody responses to T
      dependent antigens. Memory CD4 T cells express accelerated helper functions and
      are less dependent on costimulation when compared with naive T cells. Here, we
      report that donor-reactive memory CD4 T cells can deliver help to CD40-deficient
      B cells and induce high titers of IgG alloantibodies that contribute to heart
      allograft rejection in CD40-/- heart recipients. While cognate interactions
      between memory helper T and B cells are crucial for CD40-independent help, this
      process is not accompanied by germinal center formation and occurs despite
      inducible costimulatory blockade. Consistent with the extrafollicular nature of
      T/B cell interactions, CD40-independent help fails to maintain stable levels of
      serum alloantibody and induce differentiation of long-lived plasma cells and
      memory B cells. In summary, our data suggest that while CD40-independent help by
      memory CD4 T cells is sufficient to induce high levels of pathogenic
      alloantibody, it does not sustain long-lasting anti-donor humoral immunity and B
      cell memory responses. This information may guide the future use of CD40/CD154
      targeting therapies in transplant recipients containing donor-reactive memory T
      cells. 

PMID- 24102791
TI  - Usage patterns of 'over-the-counter' vs. prescription-strength nonsteroidal anti
      inflammatory drugs in France.
AB  - AIMS: Most risks of nonsteroidal anti-inflammatory drugs (NSAIDs) are
      pharmacological, dose and duration dependent. Usage patterns of prescription-only
      (POM) or 'over-the-counter (OTC)' NSAIDs may influence risks, but are not
      commonly described. METHODS: The Echantillon Generaliste de Beneficiaires
      database, the permanent 1/97 representative sample from the French national
      healthcare insurance systems, was queried over 2009-2010 to identify usage
      patterns, concomitant chronic diseases and cardiovascular medication in OTC and
      POM NSAID users. RESULTS: Over 2 years, 229 477 of 526 108 patients had at least
      one NSAID dispensation; 44 484 patients (19%) were dispensed only OTC NSAIDs (93%
      ibuprofen) and 121 208 (53%) only POM NSAIDs. The OTC users were younger (39.9
      vs. 47.4 years old) and more often female (57 vs. 53%); 69% of OTC users and 49%
      of POM users had only one dispensation. A mean of 14.6 defined daily doses (DDD)
      were dispensed over 2 years for OTC vs. 53 for POM; 93% OTC vs. 60% POM patients
      bought <= 30 DDD over 2 years, and 1.5 vs. 12% bought >= 90 DDD. Chronic
      comorbidities were found in 19% of OTC users vs. 28% of POM users; 24 vs. 37% had
      at least one dispensation of a cardiovascular drug over the 2 years. CONCLUSIONS:
      Most of the use of NSAIDs appears to be short term, especially for OTC-type
      NSAIDs, such as ibuprofen. The validity of risk estimates for NSAIDs extrapolated
      from clinical trials or from observational studies not including OTC-type usage
      may need to be revised.

PMID- 24102792
TI  - Histopathology of cryoballoon ablation-induced phrenic nerve injury.
AB  - INTRODUCTION: Hemi-diaphragmatic paralysis is the most common complication
      associated with cryoballoon ablation for atrial fibrillation, yet the
      histopathology of phrenic nerve injury has not been well described. METHODS AND
      RESULTS: A preclinical randomized study was conducted to characterize the
      histopathology of phrenic nerve injury induced by cryoballoon ablation and assess
      the potential for electromyographic (EMG) monitoring to limit phrenic nerve
      damage. Thirty-two dogs underwent cryoballoon ablation of the right superior
      pulmonary vein with the objective of inducing phrenic nerve injury. Animals were
      randomized 1:1 to standard monitoring (i.e., interruption of ablation upon
      reduction in diaphragmatic motion) versus EMG guidance (i.e., cessation of
      ablation upon a 30% reduction in the diaphragmatic compound motor action
      potential [CMAP] amplitude). The acute procedural endpoint was achieved in all
      dogs. Phrenic nerve injury was characterized by Wallerian degeneration, with
      subperineural injury to large myelinated axons and evidence of axonal
      regeneration. The degree of phrenic nerve injury paralleled the reduction in CMAP
      amplitude (P = 0.007). Animals randomized to EMG guidance had a lower incidence
      of acute hemi-diaphragmatic paralysis (50% vs 100%; P = 0.001), persistent
      paralysis at 30 days (21% vs 75%; multivariate odds ratio 0.12, 95% confidence
      interval [0.02, 0.69], P = 0.017), and a lesser severity of histologic injury (P
      = 0.001). Mature pulmonary vein ablation lesion characteristics, including
      circumferentiality and transmurality, were similar in both groups. CONCLUSION:
      Phrenic nerve injury induced by cryoballoon ablation is axonal in nature and
      characterized by Wallerian degeneration, with potential for recovery. An EMG
      guided approach is superior to standard monitoring in limiting phrenic nerve
      damage.

PMID- 24102793
TI  - Is an implantable cardiac monitor the standard of care for determining the
      success of atrial fibrillation ablation?

PMID- 24102794
TI  - Assessment of cardiovascular autonomic function in patients with polycystic ovary
      syndrome.
AB  - AIM: The study was conducted to assess the sympathovagal balance in patients with
      polycystic ovary syndrome (PCOS) using short-term heart rate variability (HRV)
      analysis and conventional autonomic function tests (CAFT). METHODS: Thirty-one
      newly diagnosed patients with PCOS and 30 age-matched controls were recruited.
      Body mass index (BMI), waist : hip ratio (WHR), cardiovascular parameters such as
      basal heart rate (BHR), systolic blood pressure (SBP), diastolic blood pressure
      (DBP) and rate-pressure product (RPP), and fasting blood glucose (FBG) were
      measured in both groups. Cardiovascular autonomic functions assessed were
      spectral analysis of HRV, heart rate and blood pressure response to standing
      (30:15 ratio), deep breathing (E:I ratio) and isometric handgrip (DeltaDBP(ihg)).
      RESULTS: The cases had significantly increased BMI, WHR, BHR, SBP, DBP and RPP.
      Ratio of low-frequency to high-frequency power of HRV (LF-HF ratio), the marker
      of sympathovagal balance was significantly increased in cases compared to
      controls. Time-domain indices of HRV and E:I ratio were decreased, and 30:15
      ratio, DeltaDBP(ihg) and FBG were increased in cases. Though there was a
      significant correlation of LF-HF ratio with BMI, WHR, BHR, RPP and FBG, only BHR
      and RPP had independent contribution to LF-HF ratio. CONCLUSION: We conclude that
      PCOS patients have altered autonomic modulation in the form of increased
      sympathetic and decreased parasympathetic reactivity and HRV. The sympathovagal
      imbalance exposes them to cardiovascular morbidities.

PMID- 24102795
TI  - Validation of cardiac output using real-time measurement of oxygen consumption
      during cardiac catheterization in children under 3 years of age.
AB  - OBJECTIVE: To validate a method for determination of cardiac index (CI) using
      real-time measurement of oxygen consumption (VO2 ) in young children undergoing
      cardiac catheterization. DESIGN: Retrospective review comparing thermodilution
      cardiac index (TDCI) to CI calculated by the Fick equation using real-time
      measured VO2 (RT-VO2 ) and VO2 derived from 2 published predictive equations.
      Paired t-test and Bland-Altman analysis were used to compare TDCI to Fick CI. A
      survey to ascertain pediatric cardiac catheterization practices regarding VO2
      determination was also conducted. SETTING: Quaternary care children's hospital
      cardiac catheterization laboratory. PATIENTS: Children <3 years old with
      structurally normal hearts undergoing cardiac catheterization under general
      anesthesia with at least one set of contemporaneous TDCI and RT-VO2 measurements.
      RESULTS: Thirty-six paired measurements of TDCI and RT-VO2 were made in 27
      patients over a 2-year period. Indications for catheterization included
      congenital diaphragmatic hernia postrepair (n = 13), heart disease post
      orthotopic heart transplant (n = 13), and suspected cardiomyopathy (n = 1). Mean
      age was 21.5 +/- 8 months; median weight was 9.9 kg (IQR 8.57, 12.2). RT-VO2 was
      higher than VO2 predicted by the LaFarge equation (190 +/- 31 vs. 173.8 +/- 12.8
      mL/min/m(2), P < .001), but there was no difference between TDCI and Fick CI
      calculated using VO2 from any method. Bland-Altman analysis showed excellent
      agreement between TDCI and Fick CI using RT-VO2 and VO2 predicted by the Lundell
      equation; Fick CI using VO2 predicted by the LaFarge equation showed fair
      agreement with TDCI. CONCLUSIONS: In children <3 years with a structurally normal
      heart, RT-VO2 generates highly accurate determinations of Fick CI as compared
      with TDCI. Additionally, in this population, VO2 derived from the LaFarge and
      Lundell equations generates accurate Fick CI compared with TDCI. Future studies
      are needed to identify factors associated with inaccurate VO2 generated from
      these predictive equations.

PMID- 24102796
TI  - Chlamydia screening in young people as an outcome of a HEADSS; Home, Education,
      Activities, Drug and alcohol use, Sexuality and Suicide youth psychosocial
      assessment tool.
AB  - AIMS AND OBJECTIVES: To identify the percentage of young people presenting to a
      primary healthcare service targeting homeless youth, in Melbourne, Australia,
      who, based on youth-specific Home, Education, Activities, Drug and alcohol use,
      Sexuality and Suicide (HEADSS) psychosocial assessment tool, were screened for
      the sexually transmitted infection Chlamydia and tested positive. BACKGROUND:
      Homeless young people are at high risk of poor health outcomes including sexual
      health. Chlamydia prevalence is highest in 16-24 years. Youth psychosocial
      assessment tools such as the HEADSS can engage young people and provide
      comprehensive health assessment that identifies health risks. DESIGN: A
      retrospective audit. METHODS: One hundred consecutive client files of youth who
      presented to a primary healthcare service for the first time were selected.
      Client data were collected at the health services' inner city drop-in clinic and
      clinical refuge outreach (CRO). HEADSS assessments were made on new presentations
      to identify those at risk of Chlamydia. These young people were then offered
      screening for Chlamydia using a first-pass urine sample. RESULTS: One hundred
      HEADSS assessments were audited, of which 15 were incomplete. Of the 85 completed
      HEADSS assessments, 43 were tested and 11 had Chlamydia-positive results.
      CONCLUSION: Comprehensive youth assessment tools, such as the HEADSS, can provide
      a valuable resource in identifying sexual health risks such as Chlamydia. In
      turn, skilled nursing staff can provide opportunistic screening. Early
      identification and treatment for Chlamydia can reduce the spread and sequela of
      this highly infectious STI. RELEVANCE TO CLINICAL PRACTICE: Youth health nurses
      can enhance their nursing practice in working with young people at risk of
      homelessness and improve their health outcomes by employing youth-specific
      assessments.

PMID- 24102797
TI  - Detection of high levels of Survivin-immunoglobulin M immune complex in sera from
      hepatitis C virus infected patients with cirrhosis.
AB  - AIM: The identification and surveillance of patients with liver dysfunctions and
      the discovering of new disease biomarkers are needed in the clinical practice.
      The aim of this study was to investigate on Survivin-immunoglobulin (Ig)M immune
      complex (IC) as a potential biomarker of chronic liver diseases. METHODS: Serum
      levels of Survivin-IgM were measured using an enzyme-linked immunoassay that had
      been standardized and validated in our laboratory in 262 individuals, including
      healthy subjects and patients with chronic viral hepatitis, cirrhosis and
      hepatocellular carcinoma (HCC). RESULTS: Survivin-IgM IC was lower in healthy
      subjects (median, 99.39 AU/mL) than in patients with chronic viral hepatitis
      (median, 148.03 AU/mL; P = 0.002) or with cirrhosis (median, 371.00 AU/mL; P <
      0.001). Among patients with cirrhosis, those with hepatitis C virus (HCV)
      infection showed the highest level of Survivin-IgM IC (median, 633.71 AU/mL; P <
      0.001). The receiver-operator curve analysis revealed that Survivin-IgM
      accurately distinguishes HCV correlated cirrhosis from chronic viral hepatitis
      (area under the curve [AUC], 0.738; sensitivity, 74.5%; specificity, 70.7%). A
      multivariate logistic regression model, including Survivin-IgM IC, aspartate
      aminotransferase (AST) and AST/alanine aminotransferase (ALT) ratio increased the
      prediction accuracy for the identification of the cirrhotic HCV patients (AUC,
      0.818; sensitivity, 87.2%; specificity, 65.9%). Conversely, Survivin-IgM IC
      significantly decreased in HCC patients (median, 165.72 AU/mL; P = 0.022).
      CONCLUSION: Our results suggest that Survivin-IgM immune complex may be used as a
      potential biomarker for liver damage, particularly for the identification of the
      HCV-related cirrhotic population.

PMID- 24102799
TI  - A novel membrane-bound E3 ubiquitin ligase enhances the thermal resistance in
      plants.
AB  - High temperature stress disturbs cellular homoeostasis and results in a severe
      retardation in crop growth and development. Thus, it is important to reveal the
      mechanism of plants coping with heat stress. In this study, a novel gene that we
      identified from Brassica napus, referred to as BnTR1, was found to play a key
      role in heat stress response in planta. BnTR1 is a membrane-bound RINGv (C4HC3)
      protein that displays E3 ligase activity in vitro. We demonstrated that modest
      expression of BnTR1 is sufficient to minimize adverse environmental influence and
      confers thermal resistance on development without any detrimental effects in B.
      napus and Oryza sativa. Our investigation into the action mechanism indicates
      that BnTR1 is likely to be involved in mediating Ca2+ dynamics by regulating the
      activity of calcium channels, which further alters the transcripts of heat shock
      factors and heat shock proteins contributing to plant thermotolerance. Hence, our
      study identified BnTR1 as a novel key factor underlying a conserved mechanism
      conferring thermal resistance in plants.

PMID- 24102798
TI  - Norepinephrine transporter heterozygous knockout mice exhibit altered transport
      and behavior.
AB  - The norepinephrine (NE) transporter (NET) regulates synaptic NE availability for
      noradrenergic signaling in the brain and sympathetic nervous system. Although
      genetic variation leading to a loss of NET expression has been implicated in
      psychiatric and cardiovascular disorders, complete NET deficiency has not been
      found in people, limiting the utility of NET knockout mice as a model for
      genetically driven NET dysfunction. Here, we investigate NET expression in NET
      heterozygous knockout male mice (NET(+/-) ), demonstrating that they display an
      approximately 50% reduction in NET protein levels. Surprisingly, these mice
      display no significant deficit in NET activity assessed in hippocampal and
      cortical synaptosomes. We found that this compensation in NET activity was due to
      enhanced activity of surface-resident transporters, as opposed to surface
      recruitment of NET protein or compensation through other transport mechanisms,
      including serotonin, dopamine or organic cation transporters. We hypothesize that
      loss of NET protein in the NET(+/-) mouse establishes an activated state of
      existing surface NET proteins. The NET(+/-) mice exhibit increased anxiety in the
      open field and light-dark box and display deficits in reversal learning in the
      Morris water maze. These data suggest that recovery of near basal activity in
      NET(+/-) mice appears to be insufficient to limit anxiety responses or support
      cognitive performance that might involve noradrenergic neurotransmission. The
      NET(+/-) mice represent a unique model to study the loss and resultant
      compensatory changes in NET that may be relevant to behavior and physiology in
      human NET deficiency disorders. 

PMID- 24102800
TI  - Increased epicardial adipose tissue thickness as a predictor for hypertension: a
      cross-sectional observational study.
AB  - The aim of the study was to determine whether epicardial adipose tissue thickness
      (EAT), a new cardiometabolic risk factor, is associated with essential
      hypertension. The sample included 127 asymptomatic patients with one or more
      cardiovascular risk factors consecutively referred for cardiac computed
      tomography angiography. Data were collected retrospectively and compared between
      hypertensive (n=39) and normotensive (n=88) patients. The hypertensive patients
      had a significantly higher mean EAT thickness than the normotensive group (2.81+/
      1.6 mm vs 2.07+/-1.43 mm; P=.011) and a significantly elevated mean coronary
      artery calcium score (316.8+/-512.6 vs 108.73+/-215; P=.0257). The odds ratio for
      a patient with tissue thickness >=2.4 mm having hypertension was 1.396 (95%
      confidence interval, 1.033-1.922). Factors independently associated with
      hypertension were body mass index, low-density lipoprotein, and age. A model
      score was developed using the logistic regression coefficients for calculation of
      individual risk. Hypertensive patients have significantly higher than normal EAT
      thickness. Epicardial adipose tissue thickness may serve as a risk indicator for
      hypertension and cardiovascular morbidity. 

PMID- 24102801
TI  - Ultra-processed products are becoming dominant in the global food system.
AB  - The relationship between the global food system and the worldwide rapid increase
      of obesity and related diseases is not yet well understood. A reason is that the
      full impact of industrialized food processing on dietary patterns, including the
      environments of eating and drinking, remains overlooked and underestimated. Many
      forms of food processing are beneficial. But what is identified and defined here
      as ultra-processing, a type of process that has become increasingly dominant, at
      first in high-income countries, and now in middle-income countries, creates
      attractive, hyper-palatable, cheap, ready-to-consume food products that are
      characteristically energy-dense, fatty, sugary or salty and generally obesogenic.
      In this study, the scale of change in purchase and sales of ultra-processed
      products is examined and the context and implications are discussed. Data come
      from 79 high- and middle-income countries, with special attention to Canada and
      Brazil. Results show that ultra-processed products dominate the food supplies of
      high-income countries, and that their consumption is now rapidly increasing in
      middle-income countries. It is proposed here that the main driving force now
      shaping the global food system is transnational food manufacturing, retailing and
      fast food service corporations whose businesses are based on very profitable,
      heavily promoted ultra-processed products, many in snack form. 

PMID- 24102803
TI  - Taenia crassiceps infection--an unusual presentation of a tapeworm diagnosed by
      FNA cytology and PCR.

PMID- 24102802
TI  - Lipooligosaccharide locus class of Campylobacter jejuni: sialylation is not
      needed for invasive infection.
AB  - Campylobacter jejuni is a highly diverse enteropathogen that is commonly detected
      worldwide. It can sometimes cause bacteraemia, but the bacterial characteristics
      facilitating bloodstream infection are not known. A total of 73 C. jejuni
      isolates, consecutively collected from blood-borne infections during a 10-year
      period all over Finland and for which detailed clinical information of the
      patients were available, were included. We screened the isolates by PCR for the
      lipooligosaccharide (LOS) locus class and for the presence of the putative
      virulence genes ceuE, ciaB, fucP, and virB11. The isolates were also tested for
      gamma-glutamyl transpeptidase production. The results were analysed with respect
      to the clinical characteristics of the patients, and the multilocus sequence
      types (MLSTs) and serum resistance of the isolates. LOS locus classes A, B, and
      C, which carry genes for sialylation of LOS, were detected in only 23% of the
      isolates. These isolates were not more resistant to human serum than those with
      the genes of non-sialylated LOS locus classes, but were significantly more
      prevalent among patients with underlying diseases (p 0.02). The fucose permease
      gene fucP was quite uncommon, but was associated with the isolates with the
      potential to sialylate LOS (p <0.0001). LOS locus classes and some of the
      putative virulence factors were associated with MLST clonal complexes. Although
      some of the bacterial characteristics studied here have been suggested to be
      important for the invasiveness of C. jejuni, they did not explain why the
      clinical isolates in the present study were able to cause bacteraemia.

PMID- 24102804
TI  - A validated model for predicting outcome after liver transplantation:
      implications on transplanting the extremely sick.
AB  - Given the organ shortage, there is a need to optimize outcome after liver
      transplantation (LT). We defined posttransplant hospital length of stay > 60 days
      (LOS > 60) as a surrogate of suboptimal outcome. In the first phase of the study,
      a 'Study cohort' (SC) of 643 patients was used to identify risk factors and
      construct a mathematical model to identify recipients with anticipated inferior
      results. In the second phase, a cohort of 417 patients was used for validation of
      the model ['Validation Cohort' (VC)]. In the SC, 65 patients (10.1%) had LOS > 60
      days. One- and 3-year patient/graft survival rates were 81.9%/76.1% and
      73.4%/67.4%, respectively. Patient and graft survival rates of those with LOS >
      60 days were inferior (P < 0.0001), while transplant cost was greater [3.42
      relative units (RU) vs. 1 RU, P < 0.0001]. In a multivariable analysis,
      pretransplant dialysis (P < 0.001), mechanical ventilation (P < 0.015), MELD (P <
      0.003), and age (P < 0.009) were predictors of LOS > 60 days [ROC curve - 0.75
      (95% CI 0.70, 0.81)]. In the VC, 53 patients (12.7%) were expected to have
      adverse outcome by the model. These patients had longer LOS (P < 0.0001), higher
      cost (<0.0001), and inferior patient and graft survival (P < 0.007).

PMID- 24102805
TI  - Oligomerization and higher-order assembly contribute to sub-cellular localization
      of a bacterial scaffold.
AB  - In Caulobacter crescentus, the PopZ polar scaffold protein supports asymmetric
      cell division by recruiting distinct sets of binding partners to opposite cell
      poles. To understand how polar organizing centres are established by PopZ, we
      investigated a set of mutated PopZ proteins for defects in sub-cellular
      localization and recruitment activity. We identified a domain within the C
      terminal 76 amino acids that is necessary and sufficient for accumulation as a
      single subcellular focus, a domain within the N-terminal 23 amino acids that is
      necessary for bipolar targeting, and a linker domain between these localization
      determinants that tolerates large variation. Mutations that inhibited dynamic
      PopZ localization inhibited the recruitment of other factors to cell poles.
      Mutations in the C-terminal domain also blocked discrete steps in the assembly of
      higher-order structures. Biophysical analysis of purified wild type and assembly
      defective mutant proteins indicates that PopZ self-associates into an elongated
      trimer, which readily forms a dimer of trimers through lateral contact. The final
      six amino acids of PopZ are necessary for connecting the hexamers into filaments,
      and these structures are important for sub-cellular localization. Thus, PopZ
      undergoes multiple orders of self-assembly, and the formation of an
      interconnected superstructure is a key feature of polar organization in
      Caulobacter. 

PMID- 24102806
TI  - Effect of a single autologous cord blood infusion on beta-cell and immune
      function in children with new onset type 1 diabetes: a non-randomized, controlled
      trial.
AB  - BACKGROUND: The application of autologous cord blood in children with type 1
      diabetes has been found to be safe, but not to preserve beta-cell function in a
      previous study, which, however, had not included a control group. OBJECTIVE: To
      compare the changes of metabolic and immune function over time between cord blood
      infused children and natural controls. SUBJECTS AND METHODS: Seven children with
      newly diagnosed type 1 diabetes underwent a single autologous cord blood infusion
      and 10 children were enrolled as natural controls in a non-randomized,
      controlled, open label intervention trial. Primary analyses were performed 1 year
      following cord blood infusion. Cases and controls were compared regarding
      metabolic [area under the curve (AUC) and peak C-peptide, insulin use, and HbA1c]
      and immune outcome (islet autoantibody titer and T-cell response), adjusted for
      age, gender, diabetes duration, and baseline levels. RESULTS: There were no
      significant adverse events related to the infusion. Metabolic and immune outcomes
      were not significantly different at 12 months follow-up between infused children
      and controls (e.g., adjusted p = 0.244 for AUC C-peptide, adjusted p = 0.820 for
      insulin use, adjusted p = 0.772 for peripheral regulatory T cells). Six-month
      change of AUC C-peptide correlated significantly with the number of infused CD34+
      cells (r = 0.931, p = 0.002). CONCLUSIONS: An autologous cord blood infusion does
      not change the natural course of metabolic and immune parameters after disease
      onset. However, the content of CD34+ cells in the stored blood sample might offer
      potential for improvement of future cell therapies.

PMID- 24102807
TI  - A C-type lectin receptor pathway is responsible for the pathogenesis of acute
      cyclophosphamide-induced cystitis in mice.
AB  - Hemorrhagic cystitis often arises after cyclophosphamide (CYP) administration. As
      yet, however, the mechanism involved in its pathogenesis is unknown. In this
      study, it was found that the Fc receptor gamma chain (FcRgamma)- caspase
      recruitment domain-containing protein 9 (CARD9)-dependent pathway rather than the
      myeloid differentiation primary response gene 88 (MyD88)-dependent pathway is
      involved in the pathogenesis of acute CYP-induced cystitis in mice. Rapid and
      transient production of interleukin (IL)-6 and IL-1beta was detected in the
      bladder at 4 hr, preceding IL-23 and IL-17A production and an influx of
      neutrophils, which reached a peak at 24 hr after injection. As assessed by
      weight, edema and neutrophil infiltration, cystitis was significantly attenuated
      in CARD9 knockout (KO) and FcRgammaKO mice, this attenuation being accompanied by
      impaired production of IL-1beta, IL-6, IL-23 and IL-17A. The major source of IL
      17A is the vesical gammadelta T cell population: IL-17AKO, CdeltaKO and Tyk2KO
      mice showed little IL-17A production and reduced neutrophil infiltration in the
      bladder after CYP injection. These results suggest that FcRgamma-CARD9-dependent
      production of proinflammatory cytokines such as IL-1beta, IL-6, and IL-23 and the
      subsequent activation of IL-17A-producing gammadelta T cells are at least partly
      involved in the pathogenesis of acute CYP-induced cystitis in mice. 

PMID- 24102808
TI  - Clinical grade manufacturing of human alloantigen-reactive regulatory T cells for
      use in transplantation.
AB  - Regulatory T cell (Treg) therapy has the potential to induce transplantation
      tolerance so that immunosuppression and associated morbidity can be minimized.
      Alloantigen-reactive Tregs (arTregs) are more effective at preventing graft
      rejection than polyclonally expanded Tregs (PolyTregs) in murine models. We have
      developed a manufacturing process to expand human arTregs in short-term cultures
      using good manufacturing practice-compliant reagents. This process uses CD40L
      activated allogeneic B cells to selectively expand arTregs followed by polyclonal
      restimulation to increase yield. Tregs expanded 100- to 1600-fold were highly
      alloantigen reactive and expressed the phenotype of stable Tregs. The alloantigen
      expanded Tregs had a diverse TCR repertoire. They were more potent than PolyTregs
      in vitro and more effective at controlling allograft injuries in vivo in a
      humanized mouse model. 

PMID- 24102811
TI  - Feasibility and validity of the ActiGraph GT3X accelerometer in measuring
      physical activity of Malawian toddlers.
AB  - AIM: To test the feasibility and validity of the ActiGraph GT3X accelerometer in
      measuring physical activity of rural Malawian toddlers. METHODS: Fifty-six
      children aged 16.0-18.5 months wore the accelerometer on their right hip for 7
      days. We analysed days with a minimum of 600 min of wear time, excluding night
      time and periods when the unit registered zero for 20 consecutive minutes. The
      first and last days were excluded as they were incomplete. Accelerometer counts
      were compared with coded free play video recordings to define median
      accelerometer counts for sedentary, light, moderate and vigorous activity. Count
      cut points were defined for moderate to vigorous physical activity, with
      predictive validity assessed using a second set of video recordings. RESULTS:
      Median wear time was 797 min/day, with 79% of participants completing at least
      four eligible days. Accelerometer counts were significantly higher for observed
      moderate to vigorous physical activity, than lighter activity, with cut points of
      208 counts/15 sec for vector magnitude and 35 counts/15 sec for vertical axis,
      showing sensitivity of 94.2% and 84.1% and specificity of 90.9% and 84.6%,
      respectively. CONCLUSION: The accelerometer proved a feasible and valid method of
      assessing physical activity among Malawian toddlers.

PMID- 24102810
TI  - Assessment of pain as a sequela in patients treated with intracavitary
      brachytherapy accelerated partial breast irradiation (IBAPBI): preliminary
      results of a prospective study.
AB  - To assess pain rates and relationship to radiation-induced fibrosis (RIF) in
      patients treated with intracavitary brachytherapy accelerated partial breast
      irradiation (IBAPBI). Thirty-nine patients treated with IBAPBI were assessed
      prospectively for development of pain pretreatment, 1 month post-IBAPBI, and
      every 6 months thereafter. A qualitative subjective Late Effects of Normal Tissue
      Subjective Objective Management Analytical (LENT-SOMA) questionnaire assessed
      pain. Use of pain medications was assessed as "no", "sometimes", or "regularly".
      A quantitative objective validated pressure threshold (PTH) measured pain in the
      site of IBAPBI breast (index) and its mirror-image in the nonirradiated breast
      (control). A validated tissue compliance meter (TCM) quantitatively assessed RIF
      in the index and control breasts at all time points. Mean DeltaPTH(kg) and
      DeltaTCM(mm) values reflected mean difference between the index and control
      breasts. Median follow-up is 44 months (range 5-59 months). According to LENT
      SOMA, pain occurred in 89% at 1 and 24 months, 67% at 30 months, 30% at 36
      months, 29% at 40 months, and 20% at 48 months. No patient used pain medication
      "regularly" but the use "sometimes" decreased over time: 61% at 1 month, 42% at
      18 and 24 months, 13% at 36 months, and 10% at 40 months. Mean DeltaPTH values,
      compared to Delta0 kg at baseline, peaked in absolute value by 1 month to -1.36
      kg (p < 0.0001), persisted after 18 months at -0.99 kg (p < 0.0001) and 24 months
      at -0.73 kg (p < 0.0001), and returned to nearly baseline by 40 months at -0.11
      kg (p < 0.57). Mean DeltaPTH and DeltaTCM correlated significantly with
      subjective patient reports of pain at each time point (p < 0.0001). To date, this
      is the first report to prospectively assess pain employing quantitative and
      qualitative inventories in patients treated with IBAPBI. Pain is experienced in
      the majority of patients experienced pain within the first 2 years, sometimes
      requiring a medication, and though subsides, it may persist 4 years after IBAPBI.

PMID- 24102812
TI  - The comparison between implant stability quotient and bone-implant contact
      revisited: an experiment in Beagle dog.
AB  - BACKGROUND: Resonance frequency analysis (RFA) is applied clinically for the
      assessment of implant stability, and the relevance of this application is widely
      accepted. However, the relationship between resonance frequency (RF) and other
      parameters of implant stability, such as the histomorphometrical bone-to-implant
      contact (BIC) parameter, has become controversial in the last decade. OBJECTIVE:
      To analyse and clarify the controversial relationship between RF and
      histomorphometrical BIC measurements. MATERIAL AND METHODS: A total of 36 dental
      implants (9 mm length, O 4.0 mm; Biohorizons((r)) Implant Systems Inc.,
      Birmingham, AL, USA) with a soluble blasting media (sandblasting with soluble
      particles) surface were implanted in six beagle dog mandibles. RFA assessments
      were performed with a magnetic Osstel Mentor((r)) device at the time of implant
      installation, and during the monitoring period at weeks 1, 2, 4, 6 and 8, before
      implant retrieval. The dogs were sacrificed and the implants were removed in
      block after 8, 6, 4, 2, 1 and 0 weeks, respectively. One group was obtained at
      time 0, immediately after the implantation. The samples were embedded in methyl
      methacrylate polymers (Technovit((r)) ) and cut along their long axis. BIC values
      were assessed by a non-subjective and systematic method based on backscattered
      scanning electron microscopy (BS-SEM) images. BIC% at the different time points
      was compared with the corresponding implant stability quotient (ISQ) values of
      the RFA assessment. RESULTS: No statistically significant correlation between BIC
      and ISQ values (Osstell Mentor((r)) ) was identified. The absence of a
      relationship between these two parameters is in agreement with several previous
      studies in humans and experimental animals. CONCLUSIONS: The lack of correlation
      between BIC and ISQ values suggests that ISQ as determined by RFA is not able to
      identify the relationship between RF and histomorphometrical data.

PMID- 24102809
TI  - Heteropatric speciation in a duck, Anas crecca.
AB  - Heteropatric differentiation is a mode of speciation with gene flow in which
      divergence occurs between lineages that are in sympatry and allopatry at
      different times during cyclic spatial movements. Empirical evidence suggests that
      heteropatric differentiation may prove to be common among seasonally migratory
      organisms. We examined genetic differentiation between the sedentary Aleutian
      Islands population of green-winged teal (Anas crecca-nimia) and its close
      migratory relative, the Eurasian, or Old World (OW), Anas c. crecca population, a
      portion of which passes through the range of nimia during its seasonal
      migrations. We also examined its relationship with the parapatric North American,
      New World (NW), A. c. carolinensis population. Sequence data from eight nuclear
      introns and the mtDNA control region showed that the nimia-crecca divergence
      occurred much more recently than the deeper crecca-carolinensis split (~83 000
      years vs. ~1.1 Myr). Despite considerable spatial overlap between crecca and
      nimia during seasonal migration, three key predictions of heteropatric
      differentiation are supported: significant genetic divergence (overall mean Phist
      = 0.07), low gene flow (2Ne m ~ 1.8), and an effective population size in nimia
      that is not especially low (Ne  ~ 80 000 individuals). Similar levels of gene
      flow have come into nimia from carolinensis, but no detectable nuclear gene flow
      has gone out of nimia into either OW (crecca) or NW (carolinensis) populations.
      We infer that adaptations of these populations to local optima in different
      places (e.g. each matching their reproductive effort to different resource
      blooms) promote genetic isolation and divergence despite periods of sympatry
      between them, as the heteropatric model predicts. 

PMID- 24102813
TI  - An interobserver reproducibility study on invasiveness of bladder cancer using
      virtual microscopy and heatmaps.
AB  - AIMS: The distinction between non-invasive (pTa) and invasive (pT1) non-muscle
      invasive bladder cancer (NMIBC) is subject to considerable interobserver
      variation. We aimed to generate a teaching set of images based on the diagnostic
      opinions of a panel of expert genitourinary pathologists. METHODS AND RESULTS:
      Twenty-five transurethral resection specimens initially reported as pT1 NMIBC
      from two university hospitals were selected on the basis of potential uncertainty
      of stromal invasion. Digitized slides were reviewed independently by a panel of
      eight genitourinary pathologists, who annotated any invasive area if present.
      Annotations were reviewed by the lead panel, and heatmaps of annotated areas were
      constructed. Reasons for discrepancies were analysed, and kappa scores were
      calculated to determine agreement among the eight panellists. Full agreement by
      the eight panellists was obtained in 11 of 25 cases (44%), with a multi-rater
      (Fleiss) kappa of 0.47 (P < 0.0001). After joint review of the seven discordant
      (agreement <75% of panellists) cases, consensus was obtained for six cases, and a
      teaching set of images was generated. CONCLUSIONS: Interobserver agreement among
      the panellists in the selected cases was moderate, but consensus could be reached
      in almost all cases. Heatmaps proved to be instrumental in generating a teaching
      set of images for standardization of histological criteria for NMIBC invasion.

PMID- 24102814
TI  - Quantitative trait loci for growth and body size in the nine-spined stickleback
      Pungitius pungitius L.
AB  - Body size is an ecologically important trait shown to be genetically variable
      both within and among different animal populations as revealed by quantitative
      genetic studies. However, few studies have looked into underlying genetic
      architecture of body size variability in the wild using genetic mapping methods.
      With the aid of quantitative trait loci (QTL) analyses based on 226
      microsatellite markers, we mapped body size and growth rate traits in the nine
      spined stickleback (Pungitius pungitius) using an F2 -intercross (n = 283
      offspring) between size-divergent populations. In total, 17 QTL locations were
      detected. The proportion of phenotypic variation explained by individual body
      size-related QTL ranged from 3% to 12% and those related to growth parameters and
      increments from 3% to 10%. Several of the detected QTL affected either early or
      late growth. These results provide a solid starting point for more in depth
      investigations of structure and function of genomic regions involved in
      determination of body size in this popular model of ecological and evolutionary
      research. 

PMID- 24102815
TI  - Pregnancy-associated osteoporosis presenting severe vertebral fractures.
AB  - The syndrome of pregnancy-associated osteoporosis (PAO) is a rare disorder which
      occurs either in late pregnancy or early post-partum period leading to fragility
      fracture(s), most commonly in the vertebral bodies. We presented two cases with
      PAO who had compression fractures at multiple levels involving five vertebrae in
      one case and 10 vertebrae in the other. Their spinal bone mineral density values
      were below -2.5 standard deviations. Anti-osteoporotic treatments with nasal
      calcitonin 400 IU/day, vitamin D 300.000 IU single dose, calcium 1000 mg/day,
      vitamin D 880 IU/day were initiated. In one case, kyphoplasty was performed by a
      spinal surgeon. In addition to a thoracolumbosacral orthosis, a rehabilitation
      program including muscle strengthening, range of motion, relaxation and weight
      bearing exercises was started for both cases. These cases emphasize that all
      pregnant women with complaints of back/lumbar pain should be carefully evaluated.

PMID- 24102816
TI  - Potential of a no-touch pincer ablation procedure for small hepatocellular
      carcinoma that uses a multipolar radiofrequency ablation system: An experimental
      animal study.
AB  - AIM: Treatment of hepatocellular carcinoma located on the liver surface is
      frequently difficult because direct puncture of the tumor must be avoided during
      needle insertion. The aim of this study was to investigate the utility of a no
      touch pincer ablation procedure that uses a multipolar radiofrequency ablation
      (RFA) system for a tumor located on the liver surface. METHODS: The experimental
      animals were three pigs, and RFA was performed with two internally cooled bipolar
      electrodes. Three ablative procedures were compared: linear insertion at regular
      13-mm intervals (pattern 1; virtual target tumor size, <10 mm); fan-shape
      insertion, maximum interval 20 mm (pattern 2; virtual target tumor size, <15 mm);
      and 25 mm (pattern 3; virtual target tumor size, <20 mm). All electrodes were
      inserted at a 30-mm depth. For patterns 1 and 2, ablation was performed on three
      other parts of the liver, and for pattern 3, ablation was performed on two other
      parts. RESULTS: For the median transverse and longitudinal diameter to the shaft,
      with the pattern 1 procedure, the ablative areas were 32 mm * 30 mm, and with the
      pattern 2 procedure, the ablative areas were 27 mm * 30 mm with carbonization of
      the liver surface. In contrast, with the pattern 3 procedure, the ablative areas
      were 45 mm * 26 mm; however, the ablative margin did not reach the surface, and
      carbonization was not apparent. CONCLUSION: The no-touch pincer ablation
      procedure (with an electrode interval of <=20 mm) may be useful when performed
      with two internally cooled bipolar electrodes for small nodules that protrude
      from the liver surface.

PMID- 24102817
TI  - Electrophysiological mapping and radiofrequency catheter ablation for ventricular
      tachycardia in a patient with peripartum cardiomyopathy.
AB  - A 38-year-old female with prior failed endocardial ablation for ventricular
      tachycardia (VT) was referred for further treatment. She had been diagnosed with
      peripartum cardiomyopathy 7 years before and had persistent left ventricular
      dysfunction with an ejection fraction of 20%. Epicardial voltage mapping showed
      extensive epicardial scar despite absence of endocardial scar. Five distinct VT
      morphologies were induced. Ablation was aided by electrogram characteristics,
      pace mapping, entrainment mapping, and establishing electrical inexcitability
      along areas of epicardial scar. After epicardial ablation no sustained VT was
      induced. She had been doing well without VT occurrence but died 1 year later
      unexpectedly at home. 

PMID- 24102818
TI  - Benign papillomas diagnosed on large-gauge vacuum-assisted core needle biopsy
      which span <1.5 cm do not need surgical excision.
AB  - The objective of our study is to determine if a carefully selected subset of
      benign breast papillomas (size <=1.5 cm) can be safely followed by imaging
      surveillance instead of immediate surgical excision. Over a 61/2-year period, 86
      breast lesions were diagnosed as a benign papilloma (BP) utilizing an 11- or 8
      gauge vacuum-assisted core needle biopsy (VACNB) device. In general, it was our
      intent to remove as much of the radiologically evident lesion as possible. These
      86 lesions underwent >=2 years of imaging surveillance, without surgical excision
      following initial detection. With >=2 years of radiologic follow-up, none of the
      86 BPs demonstrated imaging findings that necessitated repeat biopsy or surgical
      excision. Benign breast papillomas <=1.5 cm that are biopsied using an 11- or 8
      gauge VACNB device with intent to remove as much of the radiologically evident
      lesion as possible are safe to undergo serial imaging surveillance rather than
      immediate surgical excision.

PMID- 24102819
TI  - Multiplex real-time RT-qPCR for the detection of Norovirus in bottled and tap
      water using murine norovirus as a process control.
AB  - AIMS: To provide a rapid and sensitive method for detecting NoV GI and NoV GII in
      water and to evaluate the use of the murine norovirus (MNV-1) as a process
      control. METHODS AND RESULTS: The method is based on viral concentration by
      filtration on electropositive filters and direct lysis of adsorbed viruses from
      filters before RNA extraction and RT-qPCR amplification. An one-step multiplex RT
      qPCR assay was developed for the simultaneous detection of NoV GI, NoV GII and
      MNV-1. Then, water samples were artificially contaminated to determine mean virus
      recoveries and method sensitivity. The method showed a higher sensitivity for
      detecting NoV GII (10(3) genome copies per 0.5 l) than for NoV GI (10(4) genome
      copies per 0.5 l) in the presence of MNV-1 regardless of the type of water. The
      data also showed that MNV-1 is a robust option as process control. CONCLUSIONS:
      The method described provides a valuable tool for the monitoring of potential
      public health risks associated with NoV contamination in drinkable water.
      SIGNIFICANCE AND IMPACT OF STUDY: Given the increasing evidence for NoV
      involvement in food outbreaks, the one-step multiplex RT-qPCR assay we used in
      this study would be a very useful tool to investigate NoV contamination in other
      food products.

PMID- 24102820
TI  - Current concepts and systematic review of vascularized composite
      allotransplantation of the abdominal wall.
AB  - INTRODUCTION: Abdominal wall vascularized composite allotransplantation (AW-VCA)
      is a rarely utilized technique for large composite abdominal wall defects. The
      goal of this article is to systematically review the literature and current
      concepts of AW-VCA, outline the challenges ahead, and provide an outlook for the
      future. METHODS: Systematic review of the literature was performed using MEDLINE,
      EMBASE, and PubMed to identify relevant articles discussing results of AW-VCA.
      Cadaver and animal studies were excluded from the systematic review, but
      selectively included in the discussion. RESULTS: The resultant five papers report
      their results on AW-VCA(Transplantation, 85, 2008, 1607; Am J Transplant, 7,
      2007, 1304; Transplant Proc, 41, 2009, 521; Transplant Proc, 36, 2004, 1561;
      Lancet, 361, 2003, 2173). These papers represent the result of two study groups
      in which a total of 18 AW-VCA were performed in 17 patients. Two different
      operative approaches were used. Overall flap/graft survival was 88%. No mortality
      related to the transplant was reported. One cadaver study and two animal models
      were identified and separately presented (Transplant Proc, 43, 2011, 1701;
      Transplantation, 90, 2010, 1590; Journal of Surgical Research, 162, 2010, 314).
      CONCLUSION: Literature review reports AW-VCA is technically feasible with low
      morbidity and mortality. Functional outcomes are not reported and minimally
      considered. With advancements in vascularized composite allotransplantation
      research and decreasing toxicity of immunosuppression therapies and
      immunomodulatory regimens, AW-VCA can be applied in circumstances beyond
      conjunction with visceral transplantation.

PMID- 24102821
TI  - Ex vivo intracoronary gene transfer of adeno-associated virus 2 leads to superior
      transduction over serotypes 8 and 9 in rat heart transplants.
AB  - Heart transplant gene therapy requires vectors with long-lasting gene expression,
      high cardiotropism, and minimal pathological effects. Here, we examined
      transduction properties of ex vivo intracoronary delivery of adeno-associated
      virus (AAV) serotype 2, 8, and 9 in rat syngenic and allogenic heart transplants.
      Adult Dark Agouti (DA) rat hearts were intracoronarily perfused ex vivo with
      AAV2, AAV8, or AAV9 encoding firefly luciferase and transplanted heterotopically
      into the abdomen of syngenic DA or allogenic Wistar-Furth (WF) recipients. Serial
      in vivo bioluminescent imaging of syngraft and allograft recipients was performed
      for 6 months and 4 weeks, respectively. Grafts were removed for PCR-, RT-PCR, and
      luminometer analysis. In vivo bioluminescent imaging of recipients showed that
      AAV9 induced a prominent and stable luciferase activity in the abdomen, when
      compared with AAV2 and AAV8. However, ex vivo analyses revealed that
      intracoronary perfusion with AAV2 resulted in the highest heart transplant
      transduction levels in syngrafts and allografts. Ex vivo intracoronary delivery
      of AAV2 resulted in efficient transgene expression in heart transplants, whereas
      intracoronary AAV9 escapes into adjacent tissues. In terms of cardiac
      transduction, these results suggest AAV2 as a potential vector for gene therapy
      in preclinical heart transplants studies, and highlight the importance of
      delivery route in gene transfer studies.

PMID- 24102822
TI  - Effect of a Health Belief Model-based nursing intervention on Chinese patients
      with moderate to severe chronic obstructive pulmonary disease: a randomised
      controlled trial.
AB  - AIMS AND OBJECTIVES: To test the effect of a Health Belief Model-based nursing
      intervention on healthcare outcomes in Chinese patients with moderate to severe
      COPD. BACKGROUND: The Health Belief Model (HBM) has been internationally
      validated in a variety of chronic conditions. However, nursing intervention based
      on the HBM is less explored in Chinese patients with COPD. DESIGN: A randomised
      controlled trial. METHODS: Enrolled patients were randomly assigned to the
      intervention and control groups. Patients in the intervention group received a 20
      to 30-minute HBM-based nursing intervention every 2 days during the
      hospitalisation period after disease conditions were stable, with additional
      follow-ups after discharge. Patients in the control group received routine
      nursing care. RESULTS: Patients had significantly increased scores of health
      belief and self-efficacy after receiving the HBM-based nursing intervention.
      After receiving the 3-month follow-up, patients in the intervention group had
      significantly higher mean total scores in the Health Belief Scale and the COPD
      Self-Efficacy Scale, as well as in all the subscales, than those in the control
      group except the perceived disease seriousness. Results showed that the value of
      FEV1 /FVC ratio had a significant difference between study groups before and
      after the intervention. Results also indicated that mean scores of the Dyspnea
      Scale, 6-minute walking distance and ADL were significantly different between the
      groups and between the study time-points. CONCLUSIONS: Among patients with
      moderate to severe COPD, nursing intervention based on the HBM can enhance their
      health belief and self-efficacy towards the disease management, decrease dyspnoea
      and improve exercise tolerance and ADL. RELEVANCE TO CLINICAL PRACTICE: Nurses
      can use the HBM-based intervention to enhance patients' health belief and self
      efficacy towards the management of COPD, and subsequently benefit healthcare
      outcomes.

PMID- 24102823
TI  - Strong prediction of virological response to combination therapy by IL28B gene
      variants rs12979860 and rs8099917 in chronic hepatitis C genotype 4.
AB  - BACKGROUND: A strong association between single nucleotide polymorphisms (SNPs)
      of IL28B and treatment outcomes of pegylated interferon-alpha (PEG IFNalpha) and
      ribavirin (RBV) has been shown in chronic hepatitis C (CHC) patients with
      genotype 1. AIM: This study aimed to assess two SNPs of IL28B, rs12979860 and
      rs8099917, in predicting sustained virological responses (SVR) to treatment of
      CHC patients with genotype 4 (HCV-4). The value of rs8099917 was investigated in
      carriers of unfavourable genotypes of rs12979860. METHODS: This study included
      119 CHC patients with HCV-4 receiving combination therapy. Both SNPs of IL28B
      were determined by real-time detection polymerase chain reaction. RESULTS:
      Genotypes CC/CT/TT of rs12979860 were found in 42 (35.3%), 56 (47.1%) and 21
      (17.6%) and rs8099917 TT/TG/GG were found in 74 (62.2%), 40 (33.6%) and 5 (4.2%).
      In carriers of rs12979860 CC and rs8099917 TT, the rate of SVR was 87.5 and 65.7%
      respectively. In 54 patients heterozygous for the C allele of rs12979860, testing
      of rs8099917 revealed SVR in 42.3% of carriers of the TT genotype but no such
      responses in carriers of TG or GG (P < 0.0001, OR = 47.3, 95% CI: 2.33-767.2). By
      multivariate analysis, predictors of SVR were baseline ALT (P = 0.014, OR = 6.3,
      95% CI: 1.45-27.33), rs12979860 CC (P = 0.001, OR = 13.48, 95% CI: 2.95-61.69)
      and rs8099917 TT (P = 0.027, OR = 7.5, 95% CI: 1.25-44.88). CONCLUSION: In CHC
      genotype 4 patients, favourable genotypes of both SNPs of IL28B are valuable for
      predicting SVR. Additional genotyping of rs8099917 in carriers of the
      heterozygous C allele of rs12979860 can improve the prediction of SVR.

PMID- 24102825
TI  - Prevalence of impaired awareness of hypoglycemia and identification of predictive
      symptoms in children and adolescents with type 1 diabetes.
AB  - BACKGROUND: In children with type 1 diabetes mellitus (T1DM) the prevalence of
      impaired awareness of hypoglycemia (IAH) is uncertain. This study aimed to
      ascertain this with greater precision. Secondary aims were to assess symptoms of
      hypoglycemia and which of these best predict awareness of hypoglycemia in
      children. METHODS: Questionnaires were completed by 98 children with T1DM (mean
      age 10.6 yr) and their parent(s); hospital admission data for the previous year
      were collected. Awareness of hypoglycemia was assessed using two questionnaire
      based methods that have been validated in adults. For 4 wk, participants
      performed routine blood glucose measurements and completed questionnaires after
      each episode of hypoglycemia. Principal components analysis determined how
      symptoms correlate; multinomial logistic regression models identified which
      symptom aggregate best predicted awareness status. RESULTS: The 'Gold'
      questionnaire classified a greater proportion of the participants as having IAH
      than the 'Clarke' questionnaire (68.4 vs. 22.4%). Using the 'Clarke' method, but
      not the 'Gold' method, children with IAH were younger and more likely to require
      external assistance or hospital admission. Most aged >=9 yr (98.6%) were able to
      self-assess awareness status accurately. Puberty and increasing age, augmented
      symptom scores; duration of diabetes and glycemic control had no effect. In
      contrast to adults, behavioral symptoms were the best predictors of awareness
      status. CONCLUSIONS: IAH affects a substantial minority of children and impending
      hypoglycemia may be heralded by behavioral symptoms. The 'Clarke' method was more
      effective at identifying those at increased risk and could be used as a screening
      tool.

PMID- 24102826
TI  - Overview: Bellagio Conference on Program and Policy Options for Preventing
      Obesity in the Low- and Middle-Income Countries.
AB  - The Bellagio 'Conference on Program and Policy Options for Preventing Obesity in
      the Low- and Middle-Income Countries' (LMICs) was organized to pull together the
      current. We need not reiterate the importance of this topic or the speed of
      change in eating, drinking and moving facing us across the globe. The conference
      emerges from need to significantly step up the policies and programs to reduce
      obesity by learning from some current examples of best practice and strengthening
      the role of the academic and civil society players in translating global evidence
      and experience into action at the national level. There is also a need to empower
      the younger generation of scholars and activists in these countries to carry on
      this effort. The meeting was also timely because a number of funding agencies in
      the United States, Canada and the UK, at least, are beginning to focus attention
      on this topic. This set of papers provides not only examples of existing best
      practice but also a road map ahead for LMICs in the various areas of action
      needed to reduce obesity across LMICs. The meeting highlighted critical barriers
      to implementation that have blocked many initiatives. 

PMID- 24102824
TI  - Evaluation of heritable determinants of blood and brain serotonin homeostasis
      using recombinant inbred mice.
AB  - The biogenic amine serotonin (5-HT, 5-hydroxytryptamine) exerts powerful,
      modulatory control over multiple physiological functions in the brain and
      periphery, ranging from mood and appetite to vasoconstriction and
      gastrointestinal motility. In order to gain insight into shared and distinct
      molecular and phenotypic networks linked to variations in 5-HT homeostasis, we
      capitalized on the stable genetic variation present in recombinant inbred mouse
      strains. This family of strains, all derived from crosses between C57BL/6J and
      DBA/2J (BXD) parents, represents a unique, community resource with approximately
      40 years of assembled phenotype data that can be exploited to explore and test
      causal relationships in silico. We determined levels of 5-HT and 5
      hydroxyindoleacetic acid from whole blood, midbrain and thalamus/hypothalamus
      (diencephalon) of 38 BXD lines and both sexes. All 5-HT measures proved highly
      heritable in each region, although both gender and region significantly impacted
      between-strain correlations. Our studies identified both expected and novel
      biochemical, anatomical and behavioral phenotypes linked to 5-HT traits, as well
      as distinct quantitative trait loci. Analyses of these loci nominate a group of
      genes likely to contribute to gender- and region-specific capacities for 5-HT
      signaling. Analysis of midbrain mRNA variations across strains revealed
      overlapping gene expression networks linked to 5-HT synthesis and metabolism.
      Altogether, our studies provide a rich profile of genomic, molecular and
      phenotypic networks that can be queried for novel relationships contributing risk
      for disorders linked to perturbed 5-HT signaling. 

PMID- 24102827
TI  - Postural tachycardia syndrome following human papillomavirus vaccination.
AB  - BACKGROUND AND PURPOSE: Postural tachycardia syndrome (POTS) is a heterogeneous
      disorder of the autonomic nervous system that may have an autoimmune etiology.
      METHODS: Six patients who developed new onset POTS 6 days to 2 months following
      human papillomavirus vaccination are reported. RESULTS: Three patients also had
      neurocardiogenic syncope, and three patients were diagnosed with possible small
      fiber neuropathy. Symptoms in all patients improved over 3 years with
      pharmacotherapy and non-pharmacological measures but residual symptoms persisted.
      Molecular mimicry with formation of cross-reacting autoantibodies to the
      potential targets of the autonomic ganglia, neurons, cardiac proteins or vascular
      receptors is considered as a possible pathogenesis of new onset POTS after
      immunization. CONCLUSION: Correct diagnosis of POTS and awareness that POTS may
      occur after vaccination in young women is essential for prompt and effective
      management of this condition.

PMID- 24102828
TI  - Nuclear and nucleoid localization are independently conserved functions in
      bacteriophage terminal proteins.
AB  - Bacteriophage terminal proteins (TPs) prime DNA replication and become covalently
      linked to the DNA 5'-ends. In addition, they are DNA-binding proteins that direct
      early organization of phage DNA replication at the bacterial nucleoid and,
      unexpectedly, contain nuclear localization signals (NLSs), which localize them to
      the nucleus when expressed in mammalian cells. In spite of the lack of sequence
      homology among the phage TPs, these three properties share some common features,
      suggesting a possible evolutionary common origin of TPs. We show here that NLSs
      of three different phage TPs, Phi29, PRD1 and Cp-1, are mapped within the protein
      region required for nucleoid targeting in bacteria, in agreement with a
      previously proposed common origin of DNA-binding domains and NLSs. Furthermore,
      previously reported point mutants of Phi29 TP with no nuclear localization still
      can target the bacterial nucleoid, and Cp-1 TP contains two independent NLSs,
      only one of them required for nucleoid localization. Altogether, our results show
      that nucleoid and nucleus localization sequence requirements partially overlap,
      but they can be uncoupled, suggesting that conservation of both features could
      have a common origin but, at the same time, they have been independently
      conserved during evolution. 

PMID- 24102829
TI  - Recurrent miscarriage and cervical human papillomavirus infection.
AB  - PROBLEM: To investigate the possible relationship between human papillomavirus
      (HPV) infection and recurrent miscarriage (RM). METHODS: In this retrospective
      case-control study, 49 women with unexplained RM (Group 1 - cases) and 475 women
      without any miscarriage and with at least one pregnancy at term (Group 2 -
      controls) were checked for cervical HPV infection through Hybrid Capture((r)) II
      (HC 2) or polymerase chain reaction (PCR). RESULTS: HPV+ DNA tests were detected
      in 13 (26.53%) RM women and in 294 (61.89%) control women (P < 0.001). The
      prevalence rate in HPV+DNA tests was significantly different in the 30-39 years
      age range. No differences between groups were detected in HPV types, nor in the
      cytological and histological findings. CONCLUSION: Women with RM have a lower
      prevalence of HPV+DNA tests than controls. This suggests that immune reactivity
      potentially leading to RM could be in some way protective against genital HPV
      infection.

PMID- 24102830
TI  - Coronary revascularization in lung transplant recipients with concomitant
      coronary artery disease.
AB  - Coronary artery disease (CAD) is not uncommon among lung transplant candidates.
      Several small, single-center series have suggested that short-term outcomes are
      acceptable in selected patients who undergo coronary revascularization prior to,
      or concomitant with, lung transplantation. Our objective was to evaluate
      perioperative and intermediate-term outcomes in this patient population at our
      institution. We performed a retrospective, observational cohort analysis of 898
      lung transplant recipients between 1997 and 2010. Pediatric, multivisceral, lobar
      or repeat transplantations were excluded, resulting in 791 patients for
      comparative analysis, of which 49 (median age 62, 79.6% bilateral transplant)
      underwent concurrent coronary artery bypass and 38 (median age 64, 63.2%
      bilateral transplant) received preoperative percutaneous coronary intervention
      (PCI). Perioperative mortality, overall unadjusted survival and adjusted hazard
      ratio for cumulative risk of death were similar among both revascularization
      groups as well as controls. The rate of postoperative major adverse cardiac
      events was also similar among groups; however, concurrent coronary artery bypass
      was associated with longer postoperative length of stay, more time in the
      intensive care unit and more postoperative days requiring ventilator support.
      These results suggest that patients with CAD need not be excluded from lung
      transplantation. Preferential consideration should be given to preoperative PCI
      when feasible. 

PMID- 24102831
TI  - Daytime systolic ambulatory blood pressure with a direct switch between
      candesartan monotherapy and the fixed-dose combination olmesartan/amlodipine in
      patients with uncontrolled essential hypertension (SEVICONTROL-1).
AB  - A direct switch of candesartan to the fixed-dose combination
      olmesartan/amlodipine in uncontrolled hypertension is a frequent clinical
      requirement but is not covered by current labeling. An open-label, prospective,
      single-arm phase IIIb study was performed in patients with 32 mg candesartan
      followed by olmesartan/amlodipine 40/10 mg. The primary endpoint was change in
      mean daytime systolic blood pressure (BP). Mean daytime systolic BP was reduced
      by 9.2+/-12.6 mm Hg (P<.0001) after substituting candesartan for
      olmesartan/amlodipine (baseline BP 140.2+/-9.7 mm Hg). The reduction in office BP
      was 9.4+/-18.4/4.0+/-9.6 mm Hg; P<.002). Overall, 61.3% of patients achieved a
      target BP <140/90 mm Hg using office BP and <135/85 mm Hg using ambulatory BP
      measurement. There were 8 adverse events with a possible relation to study drug
      and 1 unrelated serious adverse events. In conclusion, patients with uncontrolled
      moderate arterial hypertension being treated using candesartan monotherapy
      achieve a further reduction of BP when switched directly to a fixed-dose
      combination of olmesartan 40 mg/amlodipine 10 mg. 

PMID- 24102832
TI  - GidB mutation as a phylogenetic marker for Q1 cluster Mycobacterium tuberculosis
      isolates and intermediate-level streptomycin resistance determinant in Lisbon,
      Portugal.
AB  - Development of streptomycin resistance in Mycobacterium tuberculosis is usually
      associated with mutations in rpsL and rrs genes, although up to 50% of clinical
      streptomycin-resistant isolates may present no mutation in either of these genes.
      In the present report we investigate the role of gidB gene mutations in
      streptomycin resistance. We have analyzed 52 streptomycin-resistant and 30
      streptomycin-susceptible Mycobacterium tuberculosis clinical isolates by
      sequencing and endonuclease analysis of the gidB and rpsL genes. All clinical
      isolates were genotyped by 12-loci MIRU-VNTR. The gidB gene of 18 streptomycin
      resistant isolates was sequenced and four missense mutations were found: F12L
      (1/18), L16R (18/18), A80P (4/18) and S100F (18/18). The remaining isolates were
      screened by endonuclease analysis for mutations A80P in the gidB gene and K43R in
      the rpsL gene. Overall, mutation A80P in the gidB gene was found in eight
      streptomycin-resistant isolates and 11 streptomycin-susceptible multidrug
      resistant isolates. Also noteworthy, is the fact that gidB mutations were only
      present in isolates without rpsL and rrs mutations, all from genetic cluster Q1.
      Streptomycin quantitative drug susceptibility testing showed that isolates
      carrying the gidB A80P mutation were streptomycin intermediate-level resistant
      and that standard drug susceptibility testing yielded inconsistent results,
      probably due to borderline resistance. We conclude that gidB mutations may
      explain the high number of streptomycin-resistant strains with no mutation in
      rpsL or rrs. These mutations might occasionally confer low-level streptomycin
      resistance that will go undetected in standard susceptibility testing. 

PMID- 24102833
TI  - Evaluating an holistic assessment tool for palliative care practice.
AB  - AIMS AND OBJECTIVES: To evaluate a holistic assessment tool for palliative care
      practice. This included identifying patients' needs using the holistic tool and
      exploring the usability, applicability and barriers and facilitators towards
      implementation in practice. BACKGROUND: The delivery of effective holistic
      palliative care requires a careful assessment of the patients' needs and
      circumstances. Whilst holistic assessment of palliative care needs is advocated,
      questions exist around the appropriateness of tools to assist this process.
      DESIGN: Mixed-method research design. METHODS: Data collection involved an
      analysis of piloted holistic assessments undertaken using the tool (n = 132) and
      two focus groups with healthcare professionals (n = 10). RESULTS: The tool
      enabled health professionals to identify and gain an understanding of the needs
      of the patients, specifically in relation to the physical healthcare needs.
      Differences, however, between the analysis of the tool documentation and focus
      group responses were identified in particular areas. For example, 59 (68.8%)
      respondents had discussed preferred priorities of care with the patient; however,
      focus group comments revealed participants had concerns around this. Similarly,
      whilst over half of responses (n = 50; 57.5%) had considered a prognostic
      clinical indicator for the patient as an action, focus group results indicated
      questions around healthcare professionals' knowledge and perceived usefulness of
      such indicators. Positive aspects of the tool were that it was easy to understand
      and captured the needs of individuals. Negative aspects of the tool were that it
      was repetitive and the experience of assessors required consideration.
      CONCLUSION: The tool evaluation identified questions regarding holistic
      assessment in palliative care practice and the importance of communication.
      RELEVANCE TO CLINICAL PRACTICE: A holistic assessment tool can support patient
      assessment and identification of patients' needs in the 'real world' of
      palliative care practice, but the 'tool' is merely an aid to assist professionals
      to discuss difficult and sensitive aspects of care.

PMID- 24102834
TI  - Ectopic expression of a BZR1-1D transcription factor in brassinosteroid
      signalling enhances carotenoid accumulation and fruit quality attributes in
      tomato.
AB  - The brassinosteroid (BR) response transcription factor Brassinazole resistant 1
      (BZR1)-mediated BR signalling regulates many specific developmental processes
      including fruit ripening. Here, we report the effect of 2,4-epibrassinolide (EBR)
      and BZR1-1D overexpression on carotenoid accumulation and quality attributes of
      tomato (Solanum lycopersicum) fruit. EBR-treated pericarp discs of ethylene
      insensitive mutant, Never ripe, accumulated significantly more carotenoid than
      those of the control. The results suggest that BR seems to be involved in
      modulating pigments accumulation. When three independent transgenic lines
      overexpressing the Arabidopsis BZR1-1D were used to evaluate the role of BZR1 in
      regulating tomato fruit carotenoid accumulation and quality attributes, fruits of
      all three transgenic lines exhibited enhanced carotenoid accumulation and
      increased soluble solid, soluble sugar and ascorbic acid contents during fruit
      ripening. In addition, the fruits of two transgenic lines showed dark green
      shoulder at mature green stage, in accordance with the up-regulated expression
      level of SlGLK2, which is involved in chloroplast development. Our results
      indicate the importance of BZR1-centred BR signalling in regulating carotenoid
      accumulation and quality attributes of tomato fruit and the potential application
      of the BZR1-like(s) for improvement of nutritional quality and flavour of tomato
      through genetic engineering. 

PMID- 24102835
TI  - Efficacy of eight commercial disinfectants against Microsporum canis and
      Trichophyton spp. infective spores on an experimentally contaminated textile
      surface.
AB  - BACKGROUND: An important part of treatment of dermatophytosis is the removal of
      infective material and decontamination of the environment. It is recognized that
      the role of disinfectants is to kill infective material not removed during the
      mechanical removal of debris and gross cleaning steps. A widely used disinfectant
      in the home is a dilute solution of sodium hypochlorite. HYPOTHESIS/OBJECTIVES:
      To determine whether over-the-counter products, particularly ready-to-use
      formulations, with label claim as fungicidal are effective against Microsporum or
      Trichophyton spores isolated from cat hair. METHODS: Eight commercial
      disinfectants were tested in vitro for fungicidal efficacy using three different
      trials and a 10 min contact time, as follows: a standard 1:10 spore dilution
      suspension test; 1 and 5 mL of disinfectant solution applied to contaminated
      gauze fabric; and, to simulate home use, one and five sprays of disinfectant
      applied to contaminated gauze. Good efficacy was defined as a product that
      completely inhibited growth. RESULTS: All products completely inhibited growth in
      the suspension test. Four of eight products showed complete inhibition of growth
      of both pathogens on the textile test after 1 mL or one spray; however, all eight
      products showed complete inhibition of pathogen growth after 5 mL or five sprays.
      CONCLUSIONS AND CLINICAL IMPORTANCE: Aggressive removal of contaminated material
      followed by thorough application of commercial ready-to-use disinfectants
      labelled as fungicidal against Trichophyton mentagrophytes are alternatives to
      dilute sodium hypochlorite.

PMID- 24102836
TI  - Increase of caffeine and decrease of corticosteroids for extremely low
      birthweight infants with respiratory failure from 1997 to 2011.
AB  - AIM: To compare treatment strategies for respiratory failure in extremely low
      birthweight (ELBW) infants in Germany in 1997 to Germany, Austria and Switzerland
      in 2011. METHODS: A detailed questionnaire about treatment strategies for ELBW
      infants was sent to all German centres treating ELBW infants in 1997. A follow-up
      survey was conducted in 2011 in Germany, Austria and Switzerland. RESULTS: In
      1997 and 2011, 63.6% and 66.2% of the hospitals responded. In 2011, the response
      rate was higher in Switzerland than in Germany, and in university hospitals
      versus nonuniversity hospitals. Treatment strategies did not differ between
      university and nonuniversity hospitals as well as NICUs of different sizes in
      2011. Differences between Germany, Austria and Switzerland were minimal.
      Administration of caffeine increased significantly, whereas theophylline and
      doxapram declined (all p < 0.001). While the use of dexamethasone decreased and
      the use of hydrocortisone increased, the overall use of corticosteroids declined
      (all p < 0.001). Between 1997 and 2011, therapy with inhalations and mucolytics
      decreased (both p < 0.001), whereas the use application of diuretics did not
      change significantly. In mechanically ventilated infants, the application of
      muscle relaxants and sedation declined significantly (p = 0.009 and p < 0.001),
      whereas analgesia use did not change. CONCLUSION: Treatment strategies for
      respiratory failure in ELBW infants have changed significantly between 1997 and
      2011.

PMID- 24102837
TI  - On minimizing assignment errors and the trade-off between false positives and
      negatives in parentage analysis.
AB  - Genetic parentage analyses provide a practical means with which to identify
      parent-offspring relationships in the wild. In Harrison et al.'s study (2013a),
      we compare three methods of parentage analysis and showed that the number and
      diversity of microsatellite loci were the most important factors defining the
      accuracy of assignments. Our simulations revealed that an exclusion-Bayes theorem
      method was more susceptible to false-positive and false-negative assignments than
      other methods tested. Here, we analyse and discuss the trade-off between type I
      and type II errors in parentage analyses. We show that controlling for false
      positive assignments, without reporting type II errors, can be misleading. Our
      findings illustrate the need to estimate and report both the rate of false
      positive and false-negative assignments in parentage analyses. 

PMID- 24102838
TI  - A proactive classroom management model to enhance self-efficacy levels in
      teachers of adolescents who display disruptive behaviors.
AB  - The aims of this project were to determine teachers' self-efficacy levels at
      baseline and after participating in a proactive classroom management model
      intervention. Teachers (N = 26) were recruited from a rural middle school in a
      south central state. Data required for analysis were drawn from the Teachers'
      Sense of Efficacy Scale (long form). A statistically significant difference
      (t[25] = 7.68, p < 0.001) was noted in teachers' self-efficacy levels from pre-
      to post-intervention. Findings support the need for proactive classroom
      management training for teachers as well as the need for psychiatric and mental
      health nurse consultants within the school system. Teacher classroom management
      strategies should also include appropriate response to individual student's
      needs, effective communication, and insight regarding the behaviors of students
      from diverse backgrounds.

PMID- 24102839
TI  - Health screening dialouges.
AB  - Nurses can play an important role in community-based health screenings, which are
      a practical resource to empower people living with mental and substance use
      disorders to make positive lifestyle changes. The experiences, struggles, and
      strengths of screening participants provides insights for nurses to engage people
      in health and wellness dialogues.

PMID- 24102840
TI  - Promoting wellness of peer providers through coaching.
AB  - Peer wellness coaching is workforce innovation that empowers individuals with
      mental and substance use disorders to achieve recovery. This article briefly
      describes how this approach can help peer providers develop self-care skills to
      improve job tenure and promote satisfaction. Promising results of this new
      approach are presented.

PMID- 24102841
TI  - The role of patient experience and its influence on adherence to antidepressant
      treatment.
AB  - Major depression can be a very challenging illness and although antidepressant
      agents are shown to provide benefit, many patients do not adhere to
      antidepressant treatment guidelines. Multiple factors contribute to adherence,
      including the influence of patient experience. The purpose of this article is to
      conduct a systematic review on the influence of patient experience with
      depression and antidepressant agents on treatment adherence. Thirteen research
      articles were selected for the review and revealed that patient past experience
      with depression and antidepressant agents, vicarious experiences, beliefs and
      attitudes, and the treatment experience itself can impact adherence. It is
      important for providers to be vigilant with assessment and include patient
      experience when developing a plan of care. This approach encourages shared
      decision making and a patient-centered focus for improved management of
      depression.

PMID- 24102842
TI  - The effects of cognitive-behavioral therapy on depression, anger, and self
      control for Korean soldiers.
AB  - This quasi-experimental study examined the effects of cognitive-behavioral
      therapy (CBT) to control depression, anger, and self-control in soldiers from
      South Korea. Using a pretest-posttest design, the sample was composed of an
      experimental group (n = 16) and a control group (n = 12). The experimental group
      participated in four sessions of CBT. No significant differences were found
      between the groups with regard to demographic characteristics. Changes in the
      variables after the intervention were analyzed using Wilcoxon's signed-rank sum
      test. The depression scores decreased significantly after the intervention (z = 
      3.05, p = 0.002); whereas, the scores of state-trait anger and self-control did
      not change. In the control group, none of the outcome variable scores changed
      significantly. The results indicate that the developed CBT program might be an
      effective modality to decrease the depression of soldiers who are in military
      service.

PMID- 24102843
TI  - Mandibular bone loss in ewe induced by hypothalamic-pituitary disconnection.
AB  - PURPOSE: It is supposed that the demographic change will lead to an increase in
      patients with impaired alveolar bone conditions. Large animal models are of
      particular interest in this context as they are suitable for developing and
      testing new dental implants. Recently, we demonstrated that surgical hypothalamo
      pituitary disconnection (HPD) causes a pronounced low-turnover situation leading
      to cortical and trabecular bone loss in sheep. In this study, we aimed to
      investigate the influence of the HPD procedure on the alveolar bone. METHODS: Ten
      adult Merino ewes were randomly assigned to two groups: Control and HPD. After 6
      months, we analysed the cortical and trabecular bone of all mandibles by
      histomorphometry and high-resolution peripheral quantitative computed tomography
      (HR-pQCT). RESULTS: HPD ewes showed a significant decrease in cortical thickness
      by ~20%, a significant increase in cortical porosity by ~20% and a significant
      decrease in bone volume by ~30% in comparison with Control ewes. CONCLUSION: Our
      results underline the importance of central regulatory mechanisms of bone
      turnover. However, further studies are needed to understand these central
      regulatory elements of bone turnover in detail and to judge the value of the HPD
      sheep for dental research.

PMID- 24102844
TI  - Role of ultrasound in diagnosing isolated torsion of fallopian tube.
AB  - AIM: To summarize the ultrasonic features of isolated fallopian tube torsion
      (IFTT) by retrospectively analyzing cases presenting at our hospital. METHODS:
      This analysis was approved by the ethical committee of our hospital. Medical
      records of surgically proven IFTT patients admitted to our hospital since 2002
      were collected. Clinical features and preoperative diagnoses of the patients were
      analyzed retrospectively. Ultrasonic images were reviewed and characteristics,
      including location, size, shape, echo and vascularity of the fallopian tube, were
      summarized. RESULTS: Eleven patients with IFTT were studied. No obvious
      association was found between the torsion and menstruation cycle. Only four
      accurate diagnoses were made before the operation. Degrees of torsion ranged 360
      2160 degrees . Most of them (9/11, 81.8%) were greater than 720 degrees .
      Sonograms of the 11 patients could be classified into four types: cystic masses,
      tube-like structures, heterogeneous masses and whirlpool signs. Cystic masses
      were the most commonly seen type (4/11, 36.4%), followed by tubular structures
      (3/11, 27.3%). Whirlpool sign was believed to be the most specific sign in
      diagnosing IFTT. CONCLUSION: Through review of the authors' experiences, it is
      possible to diagnose IFTT preoperatively by ultrasound. Sonograms of the IFTT
      could be divided into four types while clinical significance of this
      classification requires further confirmation.

PMID- 24102845
TI  - Case reports of portal vein thrombosis and bile duct stenosis after stereotactic
      body radiation therapy for hepatocellular carcinoma.
AB  - The aim of this study was to evaluate portal vein and bile duct toxicity after
      stereotactic body radiation therapy (SBRT) for hepatocellular carcinoma (HCC). We
      retrospectively reviewed 63 patients who were administrated SBRT once for HCC.
      The prescribed doses were from 48 Gy in four fractions to 60 Gy in eight
      fractions. Portal vein thrombosis and bile duct stenosis were evaluated. The dose
      received by 2% of the volume (D2 ) of the portal vein and bile duct was
      calculated. Portal vein thrombosis was observed in three patients (4.8%). Common
      points of these patients were Child-Pugh class B and D2 of the portal vein 40 Gy
      or more (BED3 >=200 Gy). Bile duct stenosis was observed in one patient (1.6%).
      The patient had a history of cholangiocarcinoma and left hepatic lobectomy.
      Portal vein thrombosis may be necessary to be considered when SBRT for HCC is
      administrated to patients in higher Child-Pugh class with higher D2 of the portal
      vein. 

PMID- 24102846
TI  - Obesity as a barrier to living kidney donation: a center-based analysis.
AB  - BACKGROUND: Obesity is a major epidemic and may present a significant barrier to
      living kidney donation. The purpose of our study was to determine the frequency
      of obesity as an exclusion factor and assess how often these donors lose weight
      and donate. METHODS: A single center, retrospective analysis of 104 potential
      living kidney donors between 2008 and 2012. RESULTS: Of the 104 donors, 19 (18%)
      had a normal body mass index (BMI) of <25. Eighty-five of the 104 (82%) donors
      spanned the overweight to morbidly obese classifications. Thirty-eight (37%) were
      overweight (BMI 25-29.9). Twenty-four (23%) were categorized as class I obesity
      (BMI 30-34.9), 17 (16%) as class II obesity (BMI 35-39.9), and six (6%) as class
      III obesity (BMI >40). There were a total of 23 donors (22%) who were considered
      moderately and morbidly obese (BMI >35). Of these, only three (13%) succeeded at
      losing weight and donating. CONCLUSIONS: Obesity may be a frequent barrier to
      living kidney donation, directly leading to exclusion as a potential kidney donor
      in about one in five instances. Successful weight loss leading to donation
      appears to be infrequent, suggesting need to address obesity in the donor
      population.

PMID- 24102847
TI  - The effectiveness of domestic cook on inactivation of murine norovirus in
      experimentally infected Manila clams (Ruditapes philippinarum).
AB  - AIM: The aim of this work was to evaluate the efficacy of domestic cooking in
      inactivating Manila clams experimentally infected with murine norovirus (MNV).
      METHODS AND RESULTS: A cooking pan was modified to enable electronic temperature
      probes to be positioned to record both flesh and environment temperature. Manila
      clams were infected with 10(4) TCID 50% ml(-1) of MNV. The infected whole-in
      shell clams, divided into three replicates, were cooked on an electric stove, and
      groups of nine clams were removed from the pan at fixed intervals. Pools of three
      digestive glands were examined by virus isolation to ascertain residual viral
      load. CONCLUSION: Results showed that 10 min of cooking by a traditional domestic
      method at a temperature close to 100 degrees C, for at least 2 min, can
      completely devitalize the MNV in infected clams. This is generally the time
      needed for the majority of valves to open up. SIGNIFICANCE AND IMPACT OF THE
      STUDY: At present, it is highly recommended to label all lagoon products as
      'requiring cooking before consumption', but no specifications are given on how
      long and at what temperature they should be cooked. Our results can provide the
      consumer with useful indications on how to cook clams to prevent any risk of
      foodborne illness.

PMID- 24102848
TI  - Outflow tract ventricular tachycardia mapped to the coronary arteries: anatomical
      correlates and management strategies.
AB  - BACKGROUND: The coronary cusps have been well described as a successful site for
      ablation in patients with symptomatic outflow tract ventricular tachycardia. The
      earliest site of activation is rarely found at the ostia or into the main
      coronary arteries. The exact anatomic substrate, diagnostic characteristics, and
      therapeutic approaches for such instances are poorly understood. METHODS: We
      retrospectively reviewed outflow tract ventricular arrhythmia (OTVA) ablations
      done at Mayo Clinic Rochester from 2003 to 2011 (total VT: 414; outflow tract VT:
      106). Three cases were identified where the earliest site of activation was not
      within the cusp but rather at or within the coronary ostia (3/414 for all VT:
      0.7%; 3/106 for all OTVT: 2.8%). RESULTS: In 1 patient, the left main coronary
      artery (LMCA) was found to have electrograms (EGMs) recorded with bipolar mapping
      that preceded activation in the cusps or the left ventricular outflow tract. In 2
      cases, the right coronary ostium and proximal right coronary artery recorded the
      earliest signals. Intracardiac echocardiographic guidance was used to
      successfully ablate these arrhythmias targeting the aortic route (1 patient) or
      the right coronary cusp (2 patients), and essentially isolated the focus of
      origin from the ventricular outflow tracts. Detailed mapping of surrounding
      structures, including the atrial appendages, the contralateral outflow tract, and
      the coronary venous system excluded far-field mapping in the artery as a cause
      for early activation at the ostial location. Local EGM characteristics suggested
      an unusually lengthy supravalvar myocardial extension as the likely
      arrhythmogenic substrate. Ablation was successful without coronary arterial or
      valvular injury and without valvular or root stenosis. CONCLUSIONS: Endocardial
      ablation isolating foci of origin in the vicinity of the coronary ostia is a
      challenging procedure but can be performed safely with appropriate visualization
      and is effective in the treatment of OTVA.

PMID- 24102849
TI  - Haitian variant ctxB producing Vibrio cholerae O1 with reduced susceptibility to
      ciprofloxacin is persistent in Yavatmal, Maharashtra, India, after causing a
      cholera outbreak.
AB  - Vibrio cholerae O1 biotype El Tor producing Haitian variant Cholera Toxin (HCT)
      and showing reduced susceptibility to ciprofloxacin caused a cholera outbreak
      associated with a high case fatality rate (4.5) in India. HCT-secreting strains
      responsible for severe cholera epidemics in Orissa (India), Western Africa and
      Haiti were associated with increased mortality. There is a pressing need for an
      integrated multidisciplinary approach to combat further spread of newly emerging
      variant strains. The therapeutic effect of ciprofloxacin was diminished whereas
      use of doxycycline in moderate to severe cholera patients was found to be
      effective in outbreak management. 

PMID- 24102850
TI  - Ex vivo MRI evaluation of breast tumors: a novel tool for verifying resection of
      nonpalpable only MRI detected lesions.
AB  - A fundamental question in surgery of only magnetic resonance imaging (MRI)
      detected breast lesions is to ensure their removal when they are not palpable by
      clinical examination and surgical exploration. This is especially relevant in the
      case of small tumors, carcinoma in situ or lobular carcinoma. Thirty-nine
      patients were enrolled in the study, 21 patients with breast lesions detected by
      both conventional imaging and breast MRI (bMRI) and 18 patients with bMRI
      findings only. Preoperative bMRI allowed staging the disease and localizing the
      lesion. In the operating theater, contrast medium was injected 1 minute before
      skin incision. After removal, surgical specimens were submitted to ex vivo MRI,
      performed using a dedicated surface coil and Spair inversion recovery sequences
      for suppression of fat signal intensity. All MRI enhancing lesions were
      completely included within the surgical specimen and visualized by ex vivo MRI.
      In the first 21 patients, bMRI was able to visualize branching margins or
      satellite nodules around the core lesion, and allowed for better staging of the
      surrounding in situ carcinoma; in the last 18 patients, eight of whom were breast
      cancer type 1 susceptibility protein (BRCA) mutation carriers, bMRI identified 12
      malignant tumors, otherwise undetectable, that were all visualized by ex vivo
      MRI. This is the first description of a procedure that re-enhances breast lesions
      within a surgical specimen, demonstrating the surgical removal of nonpalpable
      breast lesions diagnosed only with bMRI. This new strategy reproduces the
      morphology and the entire extension of the primary lesion on the specimen, with
      potentially better local surgical control, reducing additional unplanned surgery.

PMID- 24102851
TI  - Simultaneous compared with sequential blood pressure measurement results in
      smaller inter-arm blood pressure differences.
AB  - There are currently few recommendations on how to assess inter-arm blood pressure
      (BP) differences. The authors compared simultaneous with sequential measurement
      on mean BP, inter-arm BP differences, and within-visit reproducibility in 240
      patients stratified according to age (<50 or >=60 years) and BP (<140/90 mm Hg or
      >=140/90 mm Hg). Three simultaneous and three sequential BP measurements were
      taken in each patient. Starting measurement type and starting arm for sequential
      measurements were randomized. Mean BP and inter-arm BP differences of the first
      pair and reproducibility of inter-arm BP differences of the first and second pair
      were compared between both methods. Mean systolic BP was 1.3+/-7.5 mm Hg lower
      during sequential compared with simultaneous measurement (P<.01). However, the
      first sequential measurement was on average higher than the second, suggesting an
      order effect. Absolute systolic inter-arm BP differences were smaller on
      simultaneous (6.2+/-6.7/3.3+/-3.5 mm Hg) compared with sequential BP measurement
      (7.8+/-7.3/4.6+/-5.6 mm Hg, P<.01 for both). Within-visit reproducibility was
      identical (both r=0.60). Simultaneous measurement of BP at both arms reduces
      order effects and results in smaller inter-arm BP differences, thereby
      potentially reducing unnecessary referral and diagnostic procedures. 

PMID- 24102853
TI  - Examining correlates of self-reported and objectively measured physical activity
      among retirement village residents.
AB  - AIM: Physical activity (PA) patterns of retirement village residents were
      investigated using self-report and objective measures. METHODS: Residents (n =
      323) from retirement villages in Perth, Australia, were surveyed on PA behaviour
      and various demographic, residency, health-related and mobility factors. Most
      participants wore accelerometers for 7 days. Retirement village managers (n = 32)
      were surveyed on village descriptive characteristics, including the provision of
      amenities and facilities. Logistic regression models examined village and
      resident characteristics associated with PA. RESULTS: Based on objective
      measurement, only 27.1% of participants were sufficiently active (n = 288).
      Walking was one of the most popular PA modes. Few village characteristics were
      associated with PA; however, villages located in more walkable neighbourhoods
      increased participants' odds of transport walking. Travelling outside the village
      daily also increased PA odds. CONCLUSIONS: Most residents were insufficiently
      active to gain health benefits. Considering individual and environmental factors,
      within the retirement village and neighbourhood settings, and associations with
      PA, warrants attention.

PMID- 24102852
TI  - Improved fibrosis staging by elastometry and blood test in chronic hepatitis C.
AB  - AIMS: Our main objective was to improve non-invasive fibrosis staging accuracy by
      resolving the limits of previous methods via new test combinations. Our secondary
      objectives were to improve staging precision, by developing a detailed fibrosis
      classification, and reliability (personalized accuracy) determination. METHODS:
      All patients (729) included in the derivation population had chronic hepatitis C,
      liver biopsy, 6 blood tests and Fibroscan. Validation populations included 1584
      patients. RESULTS: The most accurate combination was provided by using most
      markers of FibroMeter and Fibroscan results targeted for significant fibrosis,
      i.e. 'E-FibroMeter'. Its classification accuracy (91.7%) and precision (assessed
      by F difference with Metavir: 0.62 +/- 0.57) were better than those of FibroMeter
      (84.1%, P < 0.001; 0.72 +/- 0.57, P < 0.001), Fibroscan (88.2%, P = 0.011; 0.68
      +/- 0.57, P = 0.020), and a previous CSF-SF classification of FibroMeter +
      Fibroscan (86.7%, P < 0.001; 0.65 +/- 0.57, P = 0.044). The accuracy for fibrosis
      absence (F0) was increased, e.g. from 16.0% with Fibroscan to 75.0% with E
      FibroMeter (P < 0.001). Cirrhosis sensitivity was improved, e.g. E-FibroMeter:
      92.7% vs. Fibroscan: 83.3%, P = 0.004. The combination improved reliability by
      deleting unreliable results (accuracy <50%) observed with a single test (1.2% of
      patients) and increasing optimal reliability (accuracy >=85%) from 80.4% of
      patients with Fibroscan (accuracy: 90.9%) to 94.2% of patients with E-FibroMeter
      (accuracy: 92.9%), P < 0.001. The patient rate with 100% predictive values for
      cirrhosis by the best combination was twice (36.2%) that of the best single test
      (FibroMeter: 16.2%, P < 0.001). CONCLUSION: The new test combination increased:
      accuracy, globally and especially in patients without fibrosis, staging
      precision, cirrhosis prediction, and even reliability, thus offering improved
      fibrosis staging.

PMID- 24102854
TI  - Cyclic changes and relationship between peripheral and endometrial NK cells from
      women with repeated failure after artificial insemination by donor sperm.
AB  - PROBLEM: Cyclic changes of peripheral natural killer (pNK) cells and/or
      endometrial NK (eNK) cells during menstrual cycle remain controversial, and their
      relationship remains uncertain. METHOD OF STUDY: Peripheral blood and endometrial
      biopsies were simultaneously obtained from women (n = 23) undergoing artificial
      insemination with donor sperm (AID) for at least three cycles at both
      proliferative (days 9-11) and secretory phases (days 20-23) of menstrual cycle.
      The percentages of CD3(-) CD56(+), CD3(-) CD56(dim) CD16(+), CD3(-) CD56(bright)
      CD16(-) pNK, and eNK cell subsets within lymphocytes were determined by three
      color flow cytometry. The correlation between the percentages of pNK and eNK
      cells was further analyzed by Spearman's test. RESULTS: The percentages of CD3(-)
      CD56(+), CD3(-) CD56(dim) CD16(+), and CD3(-) CD56(bright ) CD16(-) pNK cells
      were not statistically different between the proliferative and secretory phases
      (P > 0.05, respectively). However, the percentages of CD3(-) CD56(+) and CD3(-)
      CD56(bright ) CD16(-) eNK cells were significantly decreased at the secretory
      phase, compared with those in the proliferative phase (P < 0.05, respectively).
      No correlation between the percentages of all pNK cell parameters and those of
      CD3(-) CD56(bright ) CD16(-) eNK cells (the major subset of NK cells in uterus)
      was found in the same women throughout the menstrual cycle (P > 0.05).
      CONCLUSION: We found a menstrual-cycle-dependent change in the percentage of eNK
      cells in women undergoing AID treatment, but not pNK cells. Moreover, the
      percentage of pNK cells may not reflect that of eNK cells during menstrual cycle.

PMID- 24102855
TI  - Comamonas testosteroni uses a chemoreceptor for tricarboxylic acid cycle
      intermediates to trigger chemotactic responses towards aromatic compounds.
AB  - Bacterial chemotaxis towards aromatic compounds has been frequently observed;
      however, knowledge of how bacteria sense aromatic compounds is limited. Comamonas
      testosteroni CNB-1 is able to grow on a range of aromatic compounds. This study
      investigated the chemotactic responses of CNB-1 to 10 aromatic compounds. We
      constructed a chemoreceptor-free, non-chemotactic mutant, CNB-1Delta20, by
      disruption of all 19 putative methyl-accepting chemotaxis proteins (MCPs) and the
      atypical chemoreceptor in strain CNB-1. Individual complementation revealed that
      a putative MCP (tagged MCP2201) was involved in triggering chemotaxis towards all
      10 aromatic compounds. The recombinant sensory domain of MCP2201 did not bind to
      3- or 4-hydroxybenzoate, protocatechuate, catechol, benzoate, vanillate and
      gentisate, but bound oxaloacetate, citrate, cis-aconitate, isocitrate, alpha
      ketoglutarate, succinate, fumarate and malate. The mutant CNB-1DeltapmdF that
      lost the ability to metabolize 4-hydroxybenzoate and protocatechuate also lost
      its chemotactic response to these compounds, suggesting that taxis towards
      aromatic compounds is metabolism-dependent. Based on the ligand profile, we
      proposed that MCP2201 triggers taxis towards aromatic compounds by sensing TCA
      cycle intermediates. Our hypothesis was further supported by the finding that
      introduction of the previously characterized pseudomonad chemoreceptor (McpS) for
      TCA cycle intermediates into CNB-1Delta20 likewise triggered chemotaxis towards
      aromatic compounds. 

PMID- 24102856
TI  - Chronic kidney disease and diabetes in the national health service: a cross
      sectional survey of the U.K. national diabetes audit.
AB  - AIMS: We investigated the prevalence of chronic kidney disease and attainment of
      therapeutic targets for HbA1c and blood pressure in a large U.K.-based diabetes
      population. METHODS: The U.K. National Diabetes Audit provided data from 1
      January 2007 to 31 March 2008. Inclusion criteria were a documented urinary
      albumin:creatinine ratio and serum creatinine. Patients were stratified according
      to chronic kidney disease stage and albuminuria status. Chronic kidney disease
      was defined as an estimated glomerular filtration rate < 60 ml min(-1) 1.73 m(-2)
      , albuminuria or both. The proportions of patients achieving nationally defined
      glycaemic and systolic blood pressure targets were determined. RESULTS: The
      cohort comprised 1,423,669 patients, of whom 868,616 (61%) met inclusion
      criteria. Of the patients analysed, 92.2% had Type 2 diabetes. A higher
      proportion of people with Type 2 diabetes (42.3%) had renal dysfunction compared
      with those with Type 1 diabetes (32.4%). Achievement of systolic blood pressure
      and HbA1c targets was poor. Among people with Type 1 diabetes, 67.8% failed to
      achieve an HbA1c < 58 mmol/mol (7.5%). Of all people with diabetes, 37.8% failed
      to achieve a systolic blood pressure < 140 mmHg. Blood pressure control was poor
      in advanced chronic kidney disease. For example, mean (standard deviation)
      systolic blood pressure rose from 128.6 (15.4) mmHg among people with Type 1
      diabetes and normal renal function to 141.0 (23.6) mmHg in those with chronic
      kidney disease stage 5 and macroalbuminuria. CONCLUSIONS: The high prevalence of
      chronic kidney disease and poor attainment of treatment targets highlights a
      large subset of the diabetes population at increased risk of cardiovascular
      mortality or progressive kidney disease.

PMID- 24102857
TI  - Kidney intragraft donor-specific antibodies as determinant of antibody-mediated
      lesions and poor graft outcome.
AB  - Allograft pathology, antibody-tissue interaction as demonstrated by C4d
      deposition and serological evidence of donor-specific antibodies (DSA) are the
      cardinal diagnostic features of antibody-mediated lesions (AML) in kidney
      transplantation. However, discrepancy between histological and serological
      findings is common, and more reliable diagnostic tools are called for. Here, we
      asked whether the in situ detection of DSA could serve as marker for AML. To that
      end, we applied the anti-HLA single antigen flow bead assay to eluates from 51
      needle core graft biopsies performed for cause. Intragraft antibody profiles were
      correlated to serum DSA (sDSA), histological data and transplant outcome. The
      prevalence and the mean number of intragraft DSA (gDSA) were lower than that of
      sDSA (15/51 gDSA+ vs. 37/51 sDSA+ patients; 1.64 gDSA vs. 2.24 sDSA per patient).
      DSA were detected in all anti-HLA antibody-positive biopsies (15/15). The
      presence of gDSA was significantly associated with (1) microcirculation lesions
      taken individually (g, cg) and analyzed in functional clusters (ptc + g + cg > 0,
      cg + mm > 0), (2) C4d positivity and (3) a worse short-term transplant outcome (p
      = 0.05). These associations were not found for patients presenting only sDSA.
      Taken together, these results indicate that gDSA is a severity marker of antibody
      mediated pathogenic process.

PMID- 24102858
TI  - A comparison of maternal calcium and magnesium levels in pre-eclamptic and
      normotensive pregnancies: an observational case-control study.
AB  - OBJECTIVE: Supplementing pregnant women at high risk of developing pre-eclampsia
      with calcium may reduce the incidence of the disease. This study examines
      differences in serum and hair concentrations of calcium and magnesium between
      women with pre-eclamptic and normotensive pregnancies. DESIGN: Observational case
      control study. SETTING: Two teaching hospitals in Cape Town, South Africa.
      POPULATION: Women with pre-eclamptic (N = 96) or normotensive (N = 96)
      pregnancies, who delivered a single, live infant. METHODS: Demographic and
      current pregnancy details were retrieved from clinical notes. Each participant
      completed a dietary questionnaire. Venous blood samples were taken from each
      participant to assess serum calcium and magnesium concentrations. Hair samples
      were obtained from all participants and calcium and magnesium levels were
      measured by inductively coupled plasma optical emission spectrometry (ICPOES).
      MAIN OUTCOME MEASURE: Hair and serum calcium and magnesium concentrations were
      compared between women with pre-eclamptic and normotensive pregnancies. RESULTS:
      Diet and socio-economic status in the two groups were similar. There was no
      significant difference in the hair calcium level between women with pre-eclamptic
      [1241 parts per million (ppm); range, 331-4654 ppm] and normotensive (1146 ppm;
      range, 480-4136 ppm) pregnancies (P = 0.5). Hair calcium levels in both groups
      were not affected by HIV infection. CONCLUSION: Woman with pre-eclampsia showed
      no difference in chronic calcium status relative to normotensive women. This
      finding does not support the current belief that the mechanism by which calcium
      supplementation reduces the risk of developing pre-eclampsia is by correcting a
      nutritional deficiency.

PMID- 24102859
TI  - Neonatal hypoxic-ischaemic encephalopathy: most deaths followed end-of-life
      decisions within three days of birth.
AB  - AIM: To investigate the circumstances surrounding end-of life decisions (EoL) of
      infants with hypoxic-ischaemic encephalopathy (HIE) and examine changes over a 10
      year period. METHODS: Retrospective chart review of all infants with HIE who died
      during 2000-2004 and 2005-2009 in a Level III Neonatal Intensive Care Unit in
      Madrid, Spain. RESULTS: Of 70 infants with HIE, 18 died during the neonatal
      period. The mean age of death was 64.4 +/- 51 h. In 17 of the 18 infants (94%),
      death was preceded by an EoL decision, four after withholding therapy (WH) and 13
      after withdrawal therapy (WDT). All infants with WH were previously stable and
      without respiratory support, while all 13 infants in the WDT group had
      respiratory support and three were unstable. The age of death was greater in the
      WH group than the WDT group (122 +/- 63 h vs 50 +/- 34; p < 0.001). After the EoL
      decision, 11 (65%) infants received sedatives. There were no differences between
      the time periods. CONCLUSION: In our cohort, most deaths in newborns with HIE
      were preceded by EoL decisions mainly within the first 3 days after birth. We did
      not find changes over the first decade of the 21st century, and death was mainly
      determined by WDT.

PMID- 24102860
TI  - Pregnancy complications and obstetric care in women with inherited bleeding
      disorders.
AB  - Women with inherited bleeding disorders (IBD) require the input of a
      multidisciplinary team to improve outcomes of pregnancy. The role of the
      haemophilia nurse within the multidisciplinary team is to provide educational and
      emotional support to the women and to facilitate and co-ordinate patient-centred
      care. Prenatal diagnosis in cases of haemophilia is an integral part of the
      management of early pregnancy with a recent drive towards non-invasive prenatal
      diagnostic techniques. There is a current lack of data on the risk of miscarriage
      and bleeding complications during pregnancy. A clear association has only been
      established in women with fibrinogen and factor XIII deficiency. In the affected
      neonate with severe bleeding disorders such as haemophilia, the risk of head
      bleeding is significant, and appropriate management of labour and delivery has an
      important impact on reducing the risk. Women with IBD are at risk of both primary
      and secondary postpartum haemorrhage. Appropriate risk assessment and advance
      planning for haemostatic cover can reduce the bleeding risk. 

PMID- 24102861
TI  - Bayesian parentage analysis reliably controls the number of false assignments in
      natural populations.
AB  - Parentage analysis in natural populations is a powerful tool for addressing a
      wide range of ecological and evolutionary questions. However, identifying parent
      offspring pairs in samples collected from natural populations is often more
      challenging than simply resolving the Mendelian pattern of shared alleles. For
      example, large numbers of pairwise comparisons and limited numbers of genetic
      markers can contribute to incorrect assignments, whereby unrelated individuals
      are falsely identified as parent-offspring pairs. Determining which parentage
      methods are the least susceptible to making false assignments is an important
      challenge facing molecular ecologists. In a recent paper, Harrison et al. (2013a)
      address this challenge by comparing three commonly used parentage methods,
      including a Bayesian approach, in order to explore the effects of varied
      proportions of sampled parents on the accuracy of parentage assignments.
      Unfortunately, Harrison et al. made a simple error in using the Bayesian
      approach, which led them to incorrectly conclude that this method could not
      control the rate of false assignment. Here, I briefly outline the basic
      principles behind the Bayesian approach, identify the error made by Harrison et
      al., and provide detailed guidelines as to how the method should be correctly
      applied. Furthermore, using the exact data from Harrison et al., I show that the
      Bayesian approach actually provides greater control over the number of false
      assignments than either of the other tested methods. Lastly, I conclude with a
      brief introduction to solomon, a recently updated version of the Bayesian
      approach that can account for genotyping error, missing data and false matching. 

PMID- 24102862
TI  - Injecting drug use among young people in Pacific Island countries and
      territories: A review of the evidence.

PMID- 24102863
TI  - Leptin levels and risk of type 2 diabetes: gender-specific meta-analysis.
AB  - This meta-analysis aimed to assess the gender-specific differences in the
      relationship between circulating leptin levels and risk of type 2 diabetes.
      Published prospective studies that reported the association of leptin levels with
      risk of type 2 diabetes for a certain gender or those that reported gender
      specific associations were considered. Dose-response relationships were assessed
      by the generalized least squares trend estimation and summary relative risks
      (RRs) with 95% confidence interval (CI) were computed with the random-effects
      model. Stratified and sensitivity analyses were also performed to investigate
      potential sources of heterogeneity. Overall, 11 prospective studies were
      identified. The summary RR for an increment in leptin levels of 1-log ng mL(-1)
      was 1.37 (95% CI, 1.13-1.66) for men and 0.96 (95% CI, 0.90-1.03) for women. The
      differences between genders were statistically significant (P for interaction =
      0.006). Subgroup and sensitivity analyses generally confirmed the robustness of
      these findings. Furthermore, the increased risk in men appeared non-linear, with
      a tendency to plateau at high levels (P for non-linearity = 0.03). Little
      evidence of publication bias was found. Collectively, higher leptin levels were
      found to be associated with elevated risk of type 2 diabetes in men but not in
      women.

PMID- 24102864
TI  - Maternal floor infarction: management of an underrecognized pathology.
AB  - Maternal floor infarction is a relatively rare condition characterized clinically
      by severe early onset fetal growth restriction with features of uteroplacental
      insufficiency. It has a very high recurrence rate and carries a significant risk
      or fetal demise. Pathological characteristics include massive and diffuse fibrin
      deposition along the decidua basalis and the perivillous space of the basal
      plate. We present a case of recurrent maternal floor infarction and propose
      diagnostic clues as well as potential therapeutic options. 

PMID- 24102865
TI  - Antibodies are forever: a study using 12-26-year-old expired antibodies.
AB  - AIMS: The aim of this study was to investigate whether the shelf-life of
      diagnostic antibodies is longer than the expiry date on the label. METHODS AND
      RESULTS: Four independent laboratories tested a small number of diagnostic
      antibodies kept at +4 degrees C for 12-26 years, and found them to work perfectly
      on routine histology sections. CONCLUSIONS: Diagnostic antibodies may have a
      workable half-life in excess of 10 years, and the emphasis on performance should
      shift to the preservation of antigenic targets in the tissue.

PMID- 24102866
TI  - Responses of iliac conduit artery and hindlimb resistance vessels to luminal
      hyperfructosemia in the anaesthetized pig.
AB  - AIMS: High fructose levels are found in diabetes mellitus, associated with high
      corn syrup diets, and have been claimed to cause hypertension. As the direct
      effects on conduit and resistance arteries have not been previously reported, we
      measured these in vivo in the anaesthetized pig with instrumented iliac arteries.
      METHODS: Experiments were performed on the iliac artery preparation in the
      anaesthetized pig: blood flow, diameter and pressure were measured in the iliac.
      RESULTS: The change in diameter of an occluded iliac artery segment filled with
      hyperfructosemic (15 MUm) blood was 89.5 +/- 22.1 MUm (mean +/- SE), contrasted
      with 7.7 +/- 13.06 MUm control (P = 0.005, paired t-test, n = 6). There was no
      significant difference when compared with blood containing both hyperfructosemic
      blood and the nitric oxide synthesis inhibitor, N(G)-nitro-l-arginine methyl
      ester (250 MUg mL(-1)). Step changes in pressure and flow were achieved by
      progressive arterial stenosis during control saline and 15 MUm min(-1) fructose
      downstream intra-arterial infusions. Linear regression of the step changes in
      blood pressure versus the instantaneous step changes in blood flow showed a
      statistically significant decrease in slope of the conductance (P < 0.001,
      analysis of covariance), indicating an increase in instantaneous peripheral
      vascular resistance. Peripheral autoregulation and conduit artery shear-stress
      mediated dilatation were not significantly altered. CONCLUSION: An elevated level
      of fructose caused dilatation of a conduit artery but constriction of resistance
      vessels. The latter effect could account, if maintained long-term, for the
      hypertension claimed to be due to hyperfuctosemia.

PMID- 24102867
TI  - Volumetric dimensional changes of autogenous bone and the mixture of
      hydroxyapatite and autogenous bone graft in humans maxillary sinus augmentation.
      A multislice tomographic study.
AB  - PURPOSE: This multislice tomographic study evaluated the dimensional changes
      after maxillary sinus augmentation using autogenous bone or a mixture of
      hydroxyapatite and autogenous bone. MATERIALS AND METHODS: Ten selected patients,
      requiring a bilateral maxillary sinus augmentation, were divided, in a split
      mouth, design as follows: control group (CG n = 10 sinus grafted with autogenous
      bone) and test group (TG, n = 10 sinus grafted with a mixture of hydroxyapatite
      and autogenous bone at 80 : 20 w/w). Follow a healing period of 15 and 180 days,
      computed tomography (CT) measurements were taken by two blinded and calibrated
      examiners to verify the volumetric dimensional changes of the both groups.
      RESULTS: The interobserver agreement obtained ranged from good to excellent for
      both groups. Both groups presented significant dimensional changes after 180 days
      period healing (P < 0.05). The volumetric reduction in test group was lower
      (25.87%) when compared with the CG (42.30%) (P < 0.05). CONCLUSION: The both
      graft materials improved the bone volumetric ability to anchorage a dental
      implant. Moreover, the mixture of HA and autogenous bone graft showed lower
      degree of resorption and higher dimensional stability when compared with
      autogenous bone graft alone, at least at 180 days of healing. The CT exam
      protocol should be used as an important tool to measure bone grafts volumetric
      alterations.

PMID- 24102868
TI  - Prevalence and risk factors of hepatocellular carcinoma in Japanese patients with
      primary biliary cirrhosis.
AB  - Primary biliary cirrhosis (PBC) tends to affect females more than males. PBC
      selectively damages intrahepatic small bile ducts, particularly interlobular bile
      ducts. The clinical presentation of PBC has changed according to recent advances
      in clinicobiological diagnosis and improvements in therapeutic effects and
      prognosis. In particular, we encounter PBC patients with hepatocellular carcinoma
      (HCC), and the number of these patients appears to have increased. The precise
      reason for the increased number of PBC patients with HCC in recent decades
      remains unknown, but recognizing the current status of carcinogenesis in PBC
      patients, identifying the associated clinicopathological risk factors and
      understanding how the pathogenesis of PBC is directly associated with HCC, is
      important. In this review, we summarize the data from two nationwide surveys
      undertaken in Japan as well as recent data from Japanese and international
      studies. 

PMID- 24102869
TI  - Breast lesion excision sample (BLES biopsy) combining stereotactic biopsy and
      radiofrequency: is it a safe and accurate procedure in case of BIRADS 4 and 5
      breast lesions?
AB  - The aim of this study was to evaluate the accuracy and safety of breast lesion
      excision system (BLES) procedure with an Intact system device, under stereotactic
      and ultrasound guidance. Retrospective data review of 32 breast lesions BI-RADS 4
      or 5 underwent Intact procedures, from March 2010 to January 2012.
      Underestimation rates of atypical ductal hyperplasia (ADH) and ductal carcinoma
      in situ (DCIS) were evaluated; percentage of complete radiologic and histologic
      removal of the breast lesion were analyzed, as were the complications due to
      procedure. Complete radiologic excision of the target lesion was achieved in all
      masses and 58.6% of calcifications. Lesion size was less than 11 mm (mean size
      5.6 mm). Underestimation of ADH and DCIS was 0% and 10%, respectively. Low
      complication rate was noted: only one hematoma. BLES appears an accurate and safe
      biopsy system for sampling nonpalpable breast lesions, especially in case of
      microcalcifications clusters categorized as BI-RADS 4 and 5.

PMID- 24102870
TI  - Correlation between myocardial fibrosis and restrictive cardiac physiology in
      patients undergoing retransplantation.
AB  - After cardiac transplant, there is often development of restrictive cardiac
      physiology. Little is known about the factors that contribute to this physiology
      and its correlation with pathology. Heart retransplantation provides a valuable
      opportunity to further understand this relationship. In this study, we
      investigated the correlation of myocardial fibrosis and restrictive physiology,
      and possible risk factors utilizing data from all retransplants at our center. A
      retrospective review of the 30 patients who underwent retransplantation at our
      institution between 1994 and 2004 was performed. Hemodynamic and imaging data
      were reviewed for the presence of restrictive physiology. Pathology reports were
      reviewed for the presence of myocardial fibrosis in the explanted hearts. The
      cohort with restrictive physiology preceding redo heart transplant had
      significantly more patients exhibiting myocardial fibrosis compared with the non
      restrictive physiology group (94.1% vs. 15.4%, p < 0.001). We found no difference
      in the immunosuppressive regimen, history of rejection, and reason for
      transplant. In our study, we observed that myocardial fibrosis is an important
      contributor to the development of restrictive physiology. Further work needs to
      be done for risk stratification and the mechanism of fibrosis development.

PMID- 24102871
TI  - Oxylipins generation in Lactobacillus helveticus in relation to unsaturated fatty
      acid supplementation.
AB  - AIMS: Oxylipins are regarded as unsaturated fatty acids (UFAs) oxidation
      products, whose accumulation in plants and fungi is associated with stress. The
      aim of this study was to investigate if a metabolic pathway from UFAs to
      oxylipins was present also in lactic acid bacteria (LAB). METHODS AND RESULTS: A
      strain of Lactobacillus helveticus, incubated in the presence of oleic, linoleic
      and linolenic acids released, after 2 h, fatty acid oxidation products, mainly C6
      , C8 , C9 aldehydes and alcohols. An experiment with total carbon labelled
      linoleic acid, in the presence or not of an oxidative stress, demonstrated that
      oxylipins, such as hexanal, octanal, nonanal, 2-octenal, 2-octanal, originated
      mainly from the oxidation of this fatty acid. CONCLUSIONS: Since lipoxygenase,
      dioxygenase and cytochrome P450 genes have never been found in L. helveticus, a
      possible pathway for linoleic conversion and oxylipins formation could include,
      as a first step, the transient formation of hydroxylated linoleic acids by fatty
      acids hydratases. However, the sequence of steps from the linoleic acid to the C6
      and C8 aldehydes needs to be more deeply investigated. SIGNIFICANCE AND IMPACT OF
      THE STUDY: Due to the multiple role of oxylipins which are flavouring agents,
      antimicrobial compounds and interspecific signalling molecules, the knowledge of
      the mechanisms involved in their biosynthesis in food related bacteria could have
      an important biotechnological impact, also allowing the overproduction of
      selected bioactive molecules.

PMID- 24102872
TI  - beta-Blockers and chronic obstructive pulmonary disease: inappropriate avoidance?
AB  - Chronic obstructive pulmonary disease (COPD) is the third leading cause of death
      in the United States and is often accompanied by one or more comorbid conditions.
      While there are established morbidity and mortality benefits of beta-blocker (BB)
      use for certain cardiovascular conditions, data suggest that clinicians are often
      reluctant to prescribe them in the presence of COPD because of concerns for
      bronchoconstriction, despite evidence that they are typically well-tolerated
      among these patients. Treatment guidelines for COPD are consistent with those for
      cardiovascular disease management and support the role of BBs in management of
      particular cardiovascular conditions, even in the presence of severe COPD.
      Adherence to these guidelines could result in significant decreases in morbidity
      and mortality among patients with COPD. Additionally, current treatments for COPD
      are often linked to increased cardiovascular disease events. Further study is
      needed to clarify and guide therapeutic management in patients with COPD. 

PMID- 24102873
TI  - Is platelet transfusion necessary in cirrhotic patients with splenomegaly?

PMID- 24102875
TI  - CT imaging to guide CTI ablation: New tricks for an old dog.

PMID- 24102876
TI  - Invasive Aspergillus niger complex infections in a Belgian tertiary care
      hospital.
AB  - The incidence of invasive infections caused by the Aspergillus niger species
      complex was 0.043 cases/10 000 patient-days in a Belgian university hospital
      (2005-2011). Molecular typing was performed on six available A. niger complex
      isolates involved in invasive disease from 2010 to 2011, revealing A.
      tubingensis, which has higher triazole minimal inhibitory concentrations, in five
      out of six cases.

PMID- 24102874
TI  - Antiretroviral medication: an emerging category of prescription drug misuse.
AB  - BACKGROUND AND OBJECTIVES: Prescription drug abuse has been a focus of public
      health concern over the past two decades with many studies addressing patterns of
      narcotic analgesic abuse and diversion. Most research in this domain has centered
      on controlled substances with known abuse liability. However, the scientific
      literature has been virtually silent regarding other prescribed medications with
      previously undocumented addictive potential, such as antiretroviral (ARV)
      medications for treatment of human immunodeficiency virus. METHODS: This article
      reviews the available evidence that suggests a growing problem of ARV diversion
      and abuse and explores the reasons for the misuse of these medications based on
      the theoretical neuropsychiatric effects of ARVs and the drug-drug interactions
      between ARVs and other drugs of abuse. RESULTS: Review of media reports and
      qualitative studies suggest that ARV medications are emerging drugs of abuse.
      Claims about the psychoactive effects of ARV medications are supported by
      scientific case reports. CONCLUSIONS AND SCIENTIFIC SIGNIFICANCE: This article
      reviews the evidence to date of an emerging problem of diversion and misuse of
      ARV medications for recreational purposes. Implications of ARV misuse and
      diversion are discussed with suggestions for future research and intervention.

PMID- 24102877
TI  - Excess inpatient mortality for those with diabetes in England.

PMID- 24102878
TI  - Organizational support in the recruitment and transition of overseas-qualified
      nurses: lessons learnt from a study tour.
AB  - The migration of nurses has been a global phenomenon, and the integration of
      overseas-qualified nurses within host countries has led to debate worldwide.
      Evidence suggests that support provided by organizations can vary and that there
      is minimal information on the nature and extent of organizational support
      required to enhance a smooth transition of overseas-qualified nurses into nursing
      practice. This explorative study tour examined the organizational support
      provided to enhance overseas-qualified nurses' transition into the nursing
      workforce in two countries. The various support mechanisms provided to overseas
      qualified nurses in different organizations include transition, acculturation,
      mentoring programs, and initial settlement assistance. The successful transition
      of overseas-qualified nurses into a host country is a complex issue. A robust
      support system for these nurses should be based on ethical considerations and a
      team approach that is linked to strong leadership. In addition, education and
      support for existing staff is essential for a successful transition of overseas
      qualified nurses into practice. Lessons learnt from this study tour might also be
      relevant to the transition of other overseas-qualified health professionals, such
      as doctors and allied health professionals, in host countries.

PMID- 24102879
TI  - Intragraft donor-specific antibody detection: a new test to dichotomize HLA
      alloantibodies into high and low injurious activity.

PMID- 24102880
TI  - Association between maternal body mass index during pregnancy, short-term
      morbidity, and increased health service costs: a population-based study.
AB  - OBJECTIVE: To investigate the impact of maternal body mass index (BMI, kg/m(2))
      on clinical complications, inpatient admissions, and additional short-term costs
      to the National Health Service (NHS) in Scotland. DESIGN: Retrospective cohort
      study using an unselected population database. SETTING: Obstetric units in
      Scotland, 2003-2010. POPULATION: A total of 124,280 singleton deliveries in
      109,592 women with a maternal BMI recorded prior to 16 weeks of gestation.
      METHODS: Population-based retrospective cohort study of singleton deliveries,
      with multivariable analysis used to assess short-term morbidity and health
      service costs. MAIN OUTCOME MEASURES: Maternal and offspring outcomes, number and
      duration of hospital admissions, and healthcare costs. RESULTS: Using
      multivariable analysis, in comparison with women of normal weight, women who were
      overweight, obese, or severely obese had an increased risk of essential
      hypertension [1.87 (1.18-2.96), 11.90 (7.18-19.72), and 36.10 (18.33-71.10)],
      pregnancy-induced hypertension [1.76 (1.60-1.95), 2.98 (2.65-3.36), and 4.48
      (3.57-5.63)], gestational diabetes [3.39 (2.30-4.99), 11.90 (7.54-18.79), and
      67.40 (37.84-120.03)], emergency caesarean section [1.94 (1.71-2.21), 3.40 (2.91
      3.96), and 14.34 (9.38-21.94)], and elective caesarean section [2.06 (1.84-2.30),
      4.61 (4.06-5.24), and 17.92 (13.20-24.34)]. Compared with women of normal weight,
      women who were underweight, overweight, obese, or severely obese were associated
      with an 8, 16, 45, and 88% increase in the number of admissions, respectively,
      and women who were overweight, obese, or severely obese were associated with a 4,
      9, and 12% increase in the duration of stay (all P < 0.001). The additional
      maternity costs [mean (95% CI), adjusted analyses] for women who were
      underweight, overweight, obese, or severely obese were L102.27 (L48.49-156.06),
      L59.89 (L41.61-78.17), L202.46 (L178.61-226.31), and L350.75 (L284.82-416.69),
      respectively. CONCLUSIONS: Maternal BMI influences maternal and neonatal
      morbidity, the number and duration of maternal and neonatal admissions, and
      health service costs.

PMID- 24102883
TI  - Role of capsular polysaccharide (CPS) in biofilm formation and regulation of CPS
      production by quorum-sensing in Vibrio vulnificus.
AB  - Extracellular polysaccharides, such as lipopolysaccharide and loosely associated
      exopolysaccharides, are essential for Vibrio vulnificus to form biofilms. The
      role of another major component of the V. vulnificus extracellular matrix,
      capsular polysaccharide (CPS), which contributes to colony opacity, has been
      characterized in biofilm formation. A CPS-deficient mutant, whose wbpP gene
      encoding UDP-GlcNAc C4-epimerase was knocked out, formed significantly more
      biofilm than wild type, due to increased hydrophobicity of the cell surface,
      adherence to abiotic surfaces and cell aggregation. To elucidate the direct
      effect of CPS on biofilm structure, extracted CPS and a CPS-degrading enzyme,
      alpha-N-acetylgalactosaminidase, were added in biofilm assays, resulting in
      reduction and increment of biofilm sizes respectively. Therefore, it is suggested
      that CPS play a critical role in determining biofilm size by restricting
      continual growth of mature biofilms. Since CPS is required after maturation, CPS
      biosynthesis should be controlled in a cell density-dependent manner, e.g. by
      quorum-sensing (QS) regulation. Analysing transcription of the CPS gene cluster
      revealed that it was activated by SmcR, a QS master regulator, via binding to the
      upstream region of the cluster. Therefore, CPS was produced when biofilm cell
      density reached high enough to turn on QS regulation and limited biofilms to
      appropriate sizes. 

PMID- 24102884
TI  - Associations for birthweight of twin pairs in south India.
AB  - AIM: The aim of this study was to determine the distribution and associations of
      birthweight in twin pairs among a population of pregnant women in south India.
      MATERIAL AND METHODS: This was a retrospective case record analysis of 705 twin
      pair pregnancies during the period 2008-2012. Associations of birthweight with
      maternal age, parity, pregnancy-induced hypertension (PIH), gestational diabetes,
      obesity, chorionicity and sex of the twin pairs was explored using bivariate and
      multivariate analysis. RESULTS: The median birthweight (4250 g, interquartile
      range 3530-4810) of dichorionic twins was significantly higher (P < 0.0001) than
      monochorionic twins (3880 g, interquartile range 3000-4380). Birthweight was
      associated with chorionicity (t = 4.04, P < 0.001), obesity (t = 2.44, P = 0.03),
      nulliparity (t = -2.87, P = 0.004), and PIH (t = -2.11, P = 0.04) in a
      multivariate linear regression model. Birthweights did not differ significantly
      between female-male and female-female pairs (t = 0.11, P = 0.81), female-male and
      male-male pairs (t = -0.62, P = 0.54) or female-female and male-male pairs (t = 
      0.78, P = 0.43) in a multivariate linear regression model. The highest
      birthweight of the twin pair did not differ significantly (t = 1.27, P = 0.21) by
      sex of the twin. CONCLUSIONS: Birthweight of twins was significantly associated
      with chorionicity, obesity, PIH and nulliparity in this population. A potential
      masculinization effect was not found as the total birthweights did not differ
      significantly by sex of the twin pairs.

PMID- 24102885
TI  - Effectiveness of intensive, group therapy for teenagers who stutter.
AB  - BACKGROUND: Treatment of adolescents who stutter is an under-researched area that
      would benefit from greater attention. AIMS: To investigate whether an intensive
      treatment programme for older teenagers who stutter, aged over 16 years of age,
      is effective in reducing overt and covert aspects of stuttering. METHODS &
      PROCEDURES: A repeated-measures, single-subject experimental design was
      replicated across participants. The study consisted of a 5-week baseline phase, 2
      week intensive treatment phase, 5-week consolidation phase and 10-month follow-up
      phase. Participants were asked to make ten video recordings at home during each
      phase, while completing a reading and a conversation task. Recordings were
      analysed in terms of the percentage of stuttered syllables using a simplified
      time-series analysis. Participants completed self-report questionnaires at
      predetermined times throughout the study. Data are presented for three males aged
      17;7, 17;11 and 18;10. OUTCOMES & RESULTS: One participant completed all required
      recordings. Difficulties were encountered collecting follow-up data with the
      other two participants and data are available up to 5 months after the intensive
      therapy phase. A significant trend of reduced frequency of stuttering was found
      for all three participants during the intensive therapy phase. This trend
      continued throughout the consolidation phase and remained significant when
      available longer-term data were included in the analysis. Participants also
      reported increased self-efficacy about speaking and reduced overt and covert
      aspects of stammering. CONCLUSIONS & IMPLICATIONS: Findings show that this
      therapy programme for teenagers had a significant treatment effect for the
      participants studied in the short- and medium-term, however longer-term data were
      not available for all participants. Issues in conducting research with this
      client group are discussed.

PMID- 24102886
TI  - Evaluation of a new experimental model to study bone healing after ridge
      expansion with simultaneous implant placement--a pilot study in minipigs.
AB  - OBJECTIVE: To evaluate the suitability of a minipig model for the study of bone
      healing and osseointegration of dental implants following bone splitting and
      expansion of narrow ridges. MATERIAL AND METHODS: In four minipigs, the
      mandibular premolars and first molars were extracted together with removal of the
      buccal bone plate. Three months later, ridge splitting and expansion was
      performed with simultaneous placement of three titanium implants per quadrant. On
      one side of the mandible, the expanded bone gap between the implants was filled
      with an alloplastic biphasic calcium phosphate (BCP) material, while the gap on
      the other side was left unfilled. A barrier membrane was placed in half of the
      quadrants. After a healing period of 6 weeks, the animals were sacrificed for
      histological evaluation. RESULTS: In all groups, no bone fractures occurred, no
      implants were lost, all 24 implants were osseointegrated, and the gap created by
      bone splitting was filled with new bone, irrespective of whether BCP or a barrier
      membrane was used. Slight exposure of five implants was observed, but did not
      lead to implant loss. The level of the most coronal bone-to-implant contact
      varied without being dependent on the use of BCP or a barrier membrane. In all
      groups, the BCP particles were not present deep in the bone-filled gap. However,
      BCP particles were seen at the crestal bone margin, where they were partly
      integrated in the new bone. CONCLUSIONS: This new minipig model holds great
      promise for studying experimental ridge splitting/expansion. However, efforts
      must be undertaken to reduce implant exposure and buccal bone resorption.

PMID- 24102887
TI  - Identification and treatment of osteochondritis dissecans of the distal sagittal
      ridge of the third metacarpal bone.
AB  - REASONS FOR PERFORMING STUDY: Osteochondritis dissecans (OCD) of the distal
      sagittal ridge of the third metacarpal bone (McIII) has not previously been
      described in the literature. OBJECTIVES: To describe the clinical, radiological
      and arthroscopic features of OCD of the distal sagittal ridge of the McIII and to
      report outcome in a series of cases. STUDY DESIGN: Retrospective case series.
      METHODS: Case records and images of horses with OCD of the distal sagittal ridge
      of the McIII admitted to a single referral centre between February 2006 and
      February 2013 were reviewed. Follow-up information was obtained by telephone
      questionnaire and/or racing performance. RESULTS: Osteochondritis dissecans of
      the distal sagittal ridge of the McIII was found in 16 lame horses; 9
      unilaterally and 7 bilaterally. Lesions were consistently identified with flexed
      lateromedial radiographs and in 21 joints in dorsopalmar projections also. These
      were arthroscopically accessible from the dorsal compartment with
      metacarpophalangeal joints maximally flexed. This permitted fragment removal and
      lesion debridement. Thirteen of 14 horses with follow-up of >=12 months post
      surgery performed athletically including 11 of 12 Thoroughbreds that raced.
      CONCLUSIONS: Unlike more proximal lesions, OCD of the distal sagittal ridge
      appears to affect the McIII preferentially. Lesions were identified on
      dorsopalmar and flexed lateromedial radiographs only and are amenable to
      arthroscopic surgery. Clinicians should be aware of the potential for OCD to
      affect the distal sagittal ridge of the McIII together with the radiographic
      projections needed to identify its presence. A modified arthroscopic approach to
      the dorsal metacarpophalangeal joint is necessary in order to access lesions.

PMID- 24102888
TI  - Estimating relatedness and inbreeding using molecular markers and pedigrees: the
      effect of demographic history.
AB  - Estimates of inbreeding and relatedness are commonly calculated using molecular
      markers, although the accuracy of such estimates has been questioned. As a
      further complication, in many situations, such estimates are required in
      populations with reduced genetic diversity, which is likely to affect their
      accuracy. We investigated the correlation between microsatellite- and pedigree
      based coefficients of inbreeding and relatedness in laboratory populations of
      Drosophila melanogaster that had passed through bottlenecks to manipulate their
      genetic diversity. We also used simulations to predict expected correlations
      between marker- and pedigree-based estimates and to investigate the influence of
      linkage between loci and null alleles. Our empirical data showed lower
      correlations between marker- and pedigree-based estimates in our control
      (nonbottleneck) population than were predicted by our simulations or those found
      in similar studies. Correlations were weaker in bottleneck populations,
      confirming that extreme reductions in diversity can compromise the ability of
      molecular estimates to detect recent inbreeding events. However, this result was
      highly dependent on the strength of the bottleneck and we did not observe or
      predict any reduction in correlations in our population that went through a
      relatively severe bottleneck of N = 10 for one generation. Our results are
      therefore encouraging, as molecular estimates appeared robust to quite severe
      reductions in genetic diversity. It should also be remembered that pedigree-based
      estimates may not capture realized identity-by-decent and that marker-based
      estimates may actually be more useful in certain situations. 

PMID- 24102889
TI  - Post-traumatic neuroma following breast surgery.

PMID- 24102890
TI  - Adenoid cystic carcinoma of the salivary gland: a clinicopathological study of 49
      cases and of metallothionein expression with regard to tumour behaviour.
AB  - AIMS: Adenoid cystic carcinoma (AdCC) of the salivary glands shows heterogeneous
      behaviour, with metastasis as a key indicator of poor prognosis. Metallothionein
      (MT) expression has been associated with poor prognosis of diverse neoplasms. We
      evaluated prognostic factors for AdCC and the role played by MT, focusing on
      metastatic behaviour. METHODS AND RESULTS: We reviewed the files of the Brazilian
      National Institute of Cancer between 1997 and 2004, obtaining 49 cases. Fourteen
      tumours had metastasized during follow-up. Among these, we identified cases
      presenting with metastasis at patient admission as showing the poorest survival
      rates. MT immunostaining of the tumours was performed (using the E9 antibody),
      and evaluated for the parameters of proportion, intensity and distribution in
      tumour cells. Extent and intensity of staining, and Quickscore (a combined
      measure of extent and intensity), were higher in metastatic than non-metastatic
      tumours (for Quickscore, P = 0.044), with highest values found for cases of early
      metastasis. Most cases showing weak staining, and all with a predominantly
      cytoplasm-restricted staining pattern, were non-metastatic. Metastatic tumours of
      solid type received higher scores than solid non-metastatic (Intensity, P =
      0.0239; Quickscore, P = 0.0481). CONCLUSIONS: Our results demonstrated metastasis
      to be the most significant indicator of poor prognosis and deterioration for
      AdCC. Consistent patterns of MT expression were observed to correlate with
      metastatic behaviour, indicating that MT may potentially serve as a prognostic
      marker for AdCC.

PMID- 24102891
TI  - Family-based interventions for reducing sedentary time in youth: a systematic
      review of randomized controlled trials.
AB  - Family involvement in interventions to reduce sedentary time may help foster
      appropriate long-term screen-based habits in children. This review systematically
      synthesized evidence from randomized controlled trials of interventions with a
      family component that targeted reduction of sedentary time, including TV viewing,
      video games and computer use, in children. MEDLINE, PubMed, PsycInfo, CINAHL and
      Embase were searched from inception through March 2012. Seventeen articles were
      considered eligible and included in the review. Studies were judged to be at low
      to-moderate risk of bias. Despite inconsistent study results, level of parental
      involvement, rather than the setting itself, appeared an important determinant of
      intervention success. Studies including a parental component of medium-to-high
      intensity were consistently associated with statistically significant changes in
      sedentary behaviours. Participant age was also identified as a determinant of
      intervention outcomes; all three studies conducted in pre-school children
      demonstrated significant decreases in sedentary time. Finally, TV exposure
      appeared to be related to changes in energy intake rather than physical activity.
      Future studies should assess the effects of greater parental involvement and
      child age on success of sedentary behaviour interventions. More research is
      required to better understand the relationship between screen time and health
      behaviours, particularly energy intake. 

PMID- 24102892
TI  - Durable response after just one cycle of belotecan-based chemotherapy in a
      patient with relapsed primary peritoneal serous carcinoma.
AB  - The efficacy of second-line chemotherapy for relapsed primary peritoneal serous
      carcinoma has been numerously reported, but reports on durable response after
      second-line therapy have been rare. We report the case of a 66-year-old woman
      with relapsed primary peritoneal serous carcinoma who showed durable response
      after just one cycle of second-line belotecan-based therapy. The response might
      be a complete pathologic remission. Considering the fact that our patient
      suffered from neutropenic sepsis during her treatment, we concluded that
      belotecan-based chemotherapy could be a good option for second-line chemotherapy
      in some selected patients, so patient selection should be carefully performed due
      to the toxicity of belotecan. 

PMID- 24102893
TI  - Respiratory arrest following ingestion of wild mushrooms in 3 dogs (2006-2011).
AB  - OBJECTIVE: To describe the clinical course, treatment, and outcome of 3 dogs with
      respiratory arrest following mushroom ingestion. CASE SERIES SUMMARY: Three dogs
      were presented for mushroom toxicosis that developed respiratory arrest. Two of
      the dogs were treated with diazepam just prior to the development of respiratory
      arrest; 1 dog received no medications prior to respiratory arrest. Of the 3 dogs,
      1 was euthanized and the remaining 2 recovered fully with assisted and mechanical
      ventilation. NEW OR UNIQUE INFORMATION PROVIDED: This is the first documentation
      of respiratory arrest associated with mushroom toxicosis in dogs.

PMID- 24102894
TI  - Concurrent and prospective associations among biological maturation, and physical
      activity at 11 and 13 years of age.
AB  - This study examined concurrent and prospective associations between objective
      measures of biological maturation, body composition and physical activity (PA) in
      adolescent males (n = 671) and females (n = 680). Participants born to women
      recruited to the Avon Longitudinal Study of Parents and Children birth cohort
      study were assessed at 11 and 13 years. Percentage of predicted adult stature was
      used as an estimate of biological maturation. PA and time sedentary was assessed
      over 7 consecutive days using Actigraph accelerometers. Body composition was
      assessed using whole-body DXA scans. At 11 and 13 years, maturity in males was
      inversely associated with accelerometer counts-per-minute (CPM) and time engaged
      in light PA, and positively associated with time sedentary. In females, maturity
      was inversely associated with accelerometer (CPM) at 11 but not 13 years.
      Adjusting for accelerometer wear times and corresponding activity levels at 11
      years, maturity and percentage fat mass at 11 years did not predict any indices
      of PA or sedentary behavior in males or females at 13 years. Whereas advanced
      maturation in males is associated with less PA and more sedentary behavior at 11
      and 13 years, maturity at 11 does not predict PA or sedentary behavior at 13
      years in either sex. 

PMID- 24102895
TI  - The homoeobox gene SIX1 alters myosin heavy chain isoform expression in mouse
      skeletal muscle.
AB  - AIM: Six1 is necessary for the genesis of several tissues, but in adults, it is
      expressed primarily in skeletal muscle where its function is unclear.
      Overexpression of Six1 with a cofactor in skeletal muscle causes slow-to-fast
      fibre-type transition. We sought to characterize the effects of a physiologically
      relevant Six1 knockdown. METHODS: The tibialis anterior (TA) muscles of C57BL/6
      mice were electroporated with Six1 knockdown vector (siRNA) or empty vector.
      Muscles were collected at 2 or 14 days after transfection for Six1 and myosin
      heavy chain (MHC) expression analysis. C2C12 mouse myoblasts were grown in
      standard conditions. Cells were cotransfected with MHC promoter vectors and Six1
      expression vectors. Cells were harvested after 4 days of differentiation.
      RESULTS: In vivo, the Six1 siRNA caused a decreased expression of Six1,1.8-fold
      (+/-0.1, P < 0.05). With decreased Six1, MHC IIB expression decreased 2.7-fold
      (+/-0.7, P = 0.04). Proportion of muscle fibres expressing MHC IIB decreased
      (45.3 +/- 4.8% vs. 65.1 +/- 7.3% in control group, P = 0.04), and total area
      expressing MHC IIB decreased with decreased Six1 (59.6 +/- 4.3% vs. 75.2 +/- 5.4%
      in control group, P < 0.05). Decreased Six1 increased MHC IIA expression 1.9-fold
      (+/-0.3, P = 0.04). In vitro, Six1 overexpression increased promoter activation
      of MHC IIB 2.9-fold (+/-0.3, P < 0.01). Six1 knockdown repressed MHC IIB promoter
      2.9-fold (+/-0.1, P < 0.05) and MHC IIX 3.7-fold (+/-0.08, P < 0.01). CONCLUSION:
      Six1 knockdown caused a fast-to-slow shift in MHC isoform, and this was confirmed
      by promoter activity of MHC genes. Six1 may ultimately control the contractile
      and metabolic properties that define muscle fibre phenotype.

PMID- 24102896
TI  - The association of flushing bother, impact, treatment satisfaction and
      discontinuation of niacin therapy.
AB  - BACKGROUND: Niacin has lipid-modifying efficacy and cardiovascular benefit, but
      is underutilised because of niacin-induced flushing (NIF). This real-world,
      prospective, observational study characterised the severity and impact of NIF
      symptoms among participants who were newly prescribed extended-release (ER)
      niacin. METHODS: Participants were surveyed daily during week 1 of therapy, at
      weeks 5, 9, 13, and at months 7, 10 and 13. Surveys included the Flushing Symptom
      Questionnaire (FSQ), which includes the Global Flushing Severity Score (GFSS)
      question, the Flushing Impact Questionnaire (FIQ) and the Treatment Satisfaction
      Questionnaire for Medication (TSQM). RESULTS: Overall, 306 participants were
      enrolled. During week 1, 30.0% of participants reported a maximum GFSS >= 4
      (moderate or greater). Mean FIQ domain scores increased with increasing flushing
      severity, primarily driven by the Irritation/Frustration domain. By week 13, only
      2.5% of participants had attained a 2 g ER niacin dose. By month 13, 43.5% (n =
      133) had discontinued ER niacin. At discontinuation, only 3.1% of participants
      had attained the 2 g dose. Over half of the participants who discontinued
      experienced flushing symptoms: 82% reported moderate to extreme flushing (GFSS >=
      4), and 68% reported severe to extreme flushing (GFSS >= 7). Participants who
      discontinued and had flushing side effects reported high degrees of impact in the
      FIQ Irritation/Frustration domain, and high dissatisfaction as a result of side
      effects, as measured by the TSQM. CONCLUSION: In a real-world setting, NIF side
      effects were bothersome and had an impact on the continuation of therapy.

PMID- 24102898
TI  - A comparison of two doses of omeprazole in the treatment of equine gastric ulcer
      syndrome: a blinded, randomised, clinical trial.
AB  - REASONS FOR PERFORMING THE STUDY: Studies on omeprazole have reported that doses
      as low as 0.7 mg/kg bwt per os are potent suppressors of acid production. Yet, to
      date, no studies have compared treatment efficacy of different doses in clinical
      cases of equine gastric ulceration. Furthermore, no studies have been performed
      to compare the healing response of the squamous and glandular mucosa to acid
      suppression therapy. OBJECTIVES: To compare: 1) the efficacy of 2 doses of
      omeprazole in the treatment of primary squamous and glandular gastric ulceration;
      and 2) the healing response of primary squamous and glandular gastric ulceration
      to acid suppression therapy. STUDY DESIGN: A blinded, randomised, dose-response
      clinical trial. METHODS: Twenty Thoroughbred racehorses with grade >=2/4
      glandular ulceration were identified on gastroscopy. Seventeen horses also had
      grade >=2/4 squamous ulceration. Horses were randomly assigned to one of 2
      groups. Horses received either 2.0 g (high dose: 4.0 mg/kg bwt) or 0.8 g (low
      dose: 1.6 mg/kg bwt) of oral omeprazole per os once daily. Gastroscopy was
      repeated at 28-35 days. RESULTS: Time and dose significantly affected grades of
      squamous (P<0.0001, P = 0.02) and glandular (P = 0.006 and 0.005) ulceration.
      Data analysis did not support our hypothesis that the lower dose would have
      similar effects (i.e. be noninferior) to the higher dose when considering ulcer
      healing and ulcer improvement. Improvement was more likely with the high dose for
      the squamous (P = 0.05) but not glandular (P = 0.4) mucosa. The percentage of
      glandular ulcers that improved was less than squamous ulcers (P = 0.02).
      CONCLUSIONS: The results suggest that a dose-response exists for the treatment of
      both squamous and glandular ulcers. Improvement of glandular ulcers was not as
      complete as observed with squamous ulcers and current equine gastric ulcer
      syndrome treatment recommendations may not be appropriate for glandular disease.

PMID- 24102897
TI  - Combination therapy of fexofenadine and montelukast is effective in prurigo
      nodularis and pemphigoid nodularis.
AB  - In this study, we report on the efficacy of combination therapy of second
      generation antihistamine antagonist, fexofenadine hydrochloride, and leukotriene
      receptor inhibitor, montelukast sodium, for the treatment of 15 prurigo nodularis
      or pemphigoid nodularis patients, in whom conventional therapy was ineffective.
      All patients received 10 mg montelukast once a day and 240 mg fexofenadine twice
      a day for 4 weeks in addition to other medications they had been taking. We
      assessed the manifestations of the lesions and itching intensity before and after
      the therapy, and we evaluated each patient as (i) markedly improved, (ii)
      improved, (iii) slightly improved, (iv) no change, (v) worse. Two patients
      (13.3%) were evaluated as markedly improved, and the lesions of one patient
      completely disappeared. Three patients (20.0%) were evaluated as improved, and
      six patients (40.0%) as slightly improved. Thus, 11 of 15 cases (73.3%) improved
      by combination therapy of fexofenadine and montelukast, in which nine cases
      (75.0%) of prurigo nodularis and two cases (66.7%) of pemphigoid nodularis were
      involved. No patients revealed any side effects. This study revealed that
      combination therapy of fexofenadine and montelukast was effective for some
      patients with conventional therapy-resistant prurigo nodularis and pemphigoid
      nodularis.

PMID- 24102899
TI  - Effectiveness of a program to facilitate recovery for people with long-term
      mental illness in Japan.
AB  - Recovery is defined as the process of developing new meaning and purpose in life
      as one grows beyond the catastrophic effects of mental illness. This study aimed
      to develop a program to facilitate recovery and examine its effectiveness in a
      randomized controlled trial. The program was developed with three components that
      enhance benefit finding, personal meaning, and a sense of happiness. Sixty-three
      participants with long-term mental illness were randomly allocated to the
      intervention group (n = 32) or the control group (n = 31). The intervention group
      attended eight 2-h group sessions, with one held every week. Recovery was
      assessed at baseline, post-intervention, and at a three-month follow-up. In the
      per-protocol analysis, after excluding those who dropped out, the intervention
      group showed significant improvement in recovery compared with the control group
      (P < 0.05). In the intention-to-treat analysis, a repeated measures analysis of
      variance did not show any significant intervention effect (time * group) (P >
      0.05). The program had the potential to facilitate recovery.

PMID- 24102901
TI  - An uncommon cause of pacemaker-mediated ventricular tachycardia.

PMID- 24102903
TI  - Relationship between orofacial function, dentofacial morphology, and bite force
      in young subjects.
AB  - OBJECTIVE: The aim was to evaluate the relationship between orofacial function,
      dentofacial morphology, and bite force in young subjects. SUBJECTS AND METHODS:
      Three hundred and sixteen subjects were divided according to dentition stage
      (early, intermediate, and late mixed and permanent dentition). Orofacial function
      was screened using the Nordic Orofacial Test-Screening (NOT-S). Orthodontic
      treatment need, bite force, lateral and frontal craniofacial dimensions and
      presence of sleep bruxism were also assessed. The results were submitted to
      descriptive statistics, normality and correlation tests, analysis of variance,
      and multiple linear regression to test the relationship between NOT-S scores and
      the studied independent variables. RESULTS: The variance of NOT-S scores between
      groups was not significant. The evaluation of the variables that significantly
      contributed to NOT-S scores variation showed that age and presence of bruxism
      related to higher NOT-S total scores, while the increase in overbite measurement
      and presence of closed lip posture related to lower scores. Bite force did not
      show a significant relationship with scores of orofacial dysfunction. No
      significant correlations between craniofacial dimensions and NOT-S scores were
      observed. CONCLUSION: Age and sleep bruxism were related to higher NOT-S scores,
      while the increase in overbite measurement and closed lip posture contributed to
      lower scores of orofacial dysfunction.

PMID- 24102902
TI  - Defects in mitochondrial fatty acid synthesis result in failure of multiple
      aspects of mitochondrial biogenesis in Saccharomyces cerevisiae.
AB  - Mitochondrial fatty acid synthesis (mtFAS) shares acetyl-CoA with the Krebs cycle
      as a common substrate and is required for the production of octanoic acid (C8)
      precursors of lipoic acid (LA) in mitochondria. MtFAS is a conserved pathway
      essential for respiration. In a genetic screen in Saccharomyces cerevisiae
      designed to further elucidate the physiological role of mtFAS, we isolated
      mutants with defects in mitochondrial post-translational gene expression
      processes, indicating a novel link to mitochondrial gene expression and
      respiratory chain biogenesis. In our ensuing analysis, we show that mtFAS, but
      not lipoylation per se, is required for respiratory competence. We demonstrate
      that mtFAS is required for mRNA splicing, mitochondrial translation and
      respiratory complex assembly, and provide evidence that not LA per se, but fatty
      acids longer than C8 play a role in these processes. We also show that mtFAS- and
      LA-deficient strains suffer from a mild haem deficiency that may contribute to
      the respiratory complex assembly defect. Based on our data and previously
      published information, we propose a model implicating mtFAS as a sensor for
      mitochondrial acetyl-CoA availability and a co-ordinator of nuclear and
      mitochondrial gene expression by adapting the mitochondrial compartment to
      changes in the metabolic status of the cell. 

PMID- 24102904
TI  - Benign hidradenoma masquerading as ductal breast cancer-a rare case of false
      positive recurrence in cancer follow-up.

PMID- 24102905
TI  - Acute cellular and antibody-mediated rejection of the pancreas allograft:
      incidence, risk factors and outcomes.
AB  - Antibody-mediated rejection (AMR) after pancreas transplantation is a recently
      identified entity. We describe the incidence of, risk factors for, and outcomes
      after AMR, and the correlation of C4d immunostaining and donor-specific antibody
      (DSA) in the diagnosis of AMR. We retrospectively analyzed 162 pancreas
      transplants in 159 patients who underwent 94 pancreas allograft biopsies between
      2006 and 2009. Univariate and multivariate analyses were performed to evaluate
      risk factors for pancreas graft AMR. One-year rejection rates and survival after
      rejection were calculated by Kaplan-Meier methods. AMR occurred in 10% of
      patients by 1-year posttransplant. Multivariate risk factors identified for AMR
      include nonprimary simultaneous pancreas-kidney (SPK) transplant, primary
      solitary pancreas (PAN) transplant and race mismatch. After pancreas rejection,
      patient survival was 100% but 20% (8 of 41) of pancreas grafts failed within 1
      year. Graft survival after acute cellular rejection (ACR), AMR and mixed
      rejection was similar. Of biopsies that stained >5% C4d, 80% were associated with
      increased Class I DSA. In summary, AMR occurs at a measurable rate after pancreas
      transplantation, and the diagnosis should be actively sought using C4d staining
      and DSA levels in patients with graft dysfunction, especially after nonprimary
      SPK and primary PAN transplantation. 

PMID- 24102906
TI  - Methods for equine preantral follicles isolation: quantitative aspects.
AB  - The aim of this study was to test the use of mechanical and mechanical-enzymatic
      methods, saline solution (SS), and PBS solution for the manipulation and
      isolation of mare ovarian preantral follicles (PAFs). The ovaries were subjected
      to mechanical isolation (mixer) alone or in association with enzymatic digestion
      (collagenase). Incubation times of 10 and 20 min were employed. In the first
      group, 4.1 +/- 4.9 PAFs were harvested with the mechanical-enzymatic method vs
      71.1 +/- 19.2 with the mechanical procedure, showing a significant difference
      between methods; using SS and PBS, these numbers were 35.7 +/- 34.3 and 39.6 +/-
      39.6, respectively, with no significant difference between solutions. In the
      second group, there was significant difference between methods, with 7.1 +/- 10.6
      follicles harvested with the mechanical-enzymatic method vs 63.2 +/- 22.9 with
      the mechanical procedure; using SS and PBS, means were 35.5 +/- 36.4 and 34.9 +/-
      31.1, respectively. The mechanical method proved more effective than the
      mechanical-enzymatic approach. Both SS and PBS can be used as a media for equine
      PAFs preparation. 

PMID- 24102907
TI  - Repeat endocarditis: analysis of risk factors based on the International
      Collaboration on Endocarditis - Prospective Cohort Study.
AB  - Repeat episodes of infective endocarditis (IE) can occur in patients who survive
      an initial episode. We analysed risk factors and 1-year mortality of patients
      with repeat IE. We considered 1874 patients enrolled in the International
      Collaboration on Endocarditis - Prospective Cohort Study between January 2000 and
      December 2006 (ICE-PCS) who had definite native or prosthetic valve IE and 1-year
      follow-up. Multivariable analysis was used to determine risk factors for repeat
      IE and 1-year mortality. Of 1874 patients, 1783 (95.2%) had single-episode IE and
      91 (4.8%) had repeat IE: 74/91 (81%) with new infection and 17/91 (19%) with
      presumed relapse. On bivariate analysis, repeat IE was associated with
      haemodialysis (p 0.002), HIV (p 0.009), injection drug use (IDU) (p < 0.001),
      Staphylococcus aureus IE (p 0.003), healthcare acquisition (p 0.006) and previous
      IE before ICE enrolment (p 0.001). On adjusted analysis, independent risk factors
      were haemodialysis (OR, 2.5; 95% CI, 1.2-5.3), IDU (OR, 2.9; 95% CI, 1.6-5.4),
      previous IE (OR, 2.8; 95% CI, 1.5-5.1) and living in the North American region
      (OR, 1.9; 95% CI, 1.1-3.4). Patients with repeat IE had higher 1-year mortality
      than those with single-episode IE (p 0.003). Repeat IE is associated with IDU,
      previous IE and haemodialysis. Clinicians should be aware of these risk factors
      in order to recognize patients who are at risk of repeat IE.

PMID- 24102908
TI  - The density and type of MECA-79-positive high endothelial venules correlate with
      lymphocytic infiltration and tumour regression in primary cutaneous melanoma.
AB  - AIMS: Tumour-infiltrating lymphocytes have prognostic value in malignant
      melanoma. High endothelial venules (HEVs) are specialized vessels present in
      lymph nodes and tertiary lymphoid organs. CCL19, CCL21 and CCR7 regulate
      lymphocyte migration through HEVs. The aim of our study was to correlate HEV
      density in cutaneous primary and metastatic malignant melanomas with
      clinicopathological parameters, and with CCL19, CCL21 and CCR7 mRNA expression.
      METHODS AND RESULTS: High endothelial venule density was evaluated by
      immunohistochemistry with a specific antibody, MECA-79, and chemokine expression
      was evaluated by real-time PCR. MECA-79-positive vessels, covered by cuboidal (C
      HEV) or flat (F-HEV) endothelium, were detected in 55% of melanomas. HEV density
      was higher in primary melanomas than in metastases. Positive correlations were
      found between C-HEV density and lymphocytic infiltration, and between F-HEV
      density and tumour regression. Cases in which the number of C-HEVs exceeded that
      of F-HEVs had higher levels of CCL19, CCL21, and CCR7. CONCLUSIONS: Our results
      support a predominant role for C-HEV in the recruitment of lymphocytes in
      cutaneous melanomas, mediated by CCL19 and CCL21, whereas the density of F-HEV
      strongly correlates with tumour regression, Therefore, cuboidal and flat HEVs may
      serve as indicators of the active and late quiescent phases, respectively, of
      tumour regression in cutaneous malignant melanoma.

PMID- 24102909
TI  - Trade policy and obesity prevention: challenges and innovation in the Pacific
      Islands.
AB  - The Pacific Island countries experience some of the highest rates of obesity in
      the world in part due to substantial dietary changes that mirror changes in the
      food supply in the region. Economic and political ties, donor aid, and trade
      links are key drivers of the changing availability and accessibility of processed
      and imported foods. Pacific Island countries have been innovative in developing
      trade-related policy approaches to create a less obesogenic food environment.
      Taxation-based approaches that affect pricing in the region include increased
      import and excise tariffs on sugared beverages and other high-sugar products,
      monosodium glutamate, and palm oil and lowered tariffs on fruits and vegetables.
      Other approaches highlight some higher-fat products through labeling and
      controlling the supply of high-fat meats. The bans on high-fat turkey tails and
      mutton flaps highlight the politics, trade agreements and donor influences that
      can be significant barriers to the pursuit of policy options. Countries that are
      not signatories to trade agreements may have more policy space for innovative
      action. However, potential effectiveness and practicality require consideration.
      The health sector's active engagement in the negotiation of trade agreements is a
      key way to support healthier trade in the region. 

PMID- 24102910
TI  - Efficacy and 9 years' follow-up of posterior intravaginal slingplasty for genital
      prolapse.
AB  - AIM: The aim of this study was to assess the long-term efficacy and complication
      rates of posterior intravaginal slingplasty (IVS) in women suffering from genital
      prolapse. MATERIAL AND METHODS: Posterior IVS or infracoccygeal sacropexy is a
      minimally invasive procedure for suspension of the vagina with the goal of
      creating new uterosacral ligaments through the insertion of a polypropylene tape.
      Forty-four patients were enrolled: 25 patients, affected by uterovaginal
      prolapse, were subjected to vaginal hysterectomy and posterior IVS; and 19
      patients, diagnosed with vaginal vault prolapse, were subjected to posterior IVS
      alone. The primary outcome for posterior IVS was 12-month, 24-month and annual 9
      year postoperative efficacy that is based on a Pelvic Organ Prolapse Quantitative
      score of -5 at point C, which describes the vaginal apex. RESULTS: Of the 44
      patients who underwent posterior IVS, none required blood transfusions with an
      average reduction of perioperative hemoglobin of 1.2 +/- 0.4 g/dl, and the
      average time of hospitalization was 4.3 +/- 0.6 days. The rate of success was
      93.18% (41/44) at 9 years' follow-up. We had only one case of extrusion (2.27%)
      and three cases of recurrence (6.82%), such as two cases of cystocele and of
      rectocele. CONCLUSIONS: Most patients interviewed confirmed that their quality of
      life improved after surgery, 86.36% of the operated patients reported that their
      sexual performance improved and that they would recommend this surgery for their
      friends. Posterior IVS was a minimally invasive surgical procedure with a high
      success rate for genital prolapse.

PMID- 24102911
TI  - Emergency visits and occupational hazards in German Shepherd police dogs (2008
      2010).
AB  - OBJECTIVE: To describe the most common reasons for emergency medical visits in
      working police dogs. DESIGN: Retrospective case control study. ANIMALS: Two
      hundred three German Shepherd dogs (GSDs); 138 police dog visits by 74 dogs and
      138 pet (control) dog visits by 129 dogs. PROCEDURES: Medical records of all GSDs
      seen in the emergency service (ES) at the University of Pennsylvania Veterinary
      Hospital from July 2008 to July 2010 were reviewed. The recorded diagnoses from
      police GSD ES visits (defined as a new problem or new episode of a recurrent
      problem) were compared to those of randomly chosen pet GSD ES visits. RESULTS:
      There were significantly more intact male police GSDs than pet GSDs. Police GSDs
      were significantly younger than pet GSDs. The most common presenting complaint in
      both groups was gastrointestinal disease (eg, vomiting, diarrhea, gastric
      dilatation and volvulus). Pet GSDs were significantly more likely to present for
      geriatric conditions (eg, central nervous system disease, cardiovascular disease,
      and neoplastic conditions). Orthopedic issues were significantly more common in
      police GSDs. CONCLUSIONS AND CLINICAL RELEVANCE: Police GSDs are more likely to
      present for orthopedic injuries and less likely to present for geriatric
      diseases. Gastrointestinal disease is not unique to the working GSD and was
      equally represented in both populations. Preventative measures for all GSDs
      should focus on minimizing gastrointestinal disease. Preventive strategies
      focusing on physical fitness and conditioning as well as selective breeding
      programs may help reduce orthopedic injuries in police GSDs.

PMID- 24102912
TI  - Continuous vs interval training on glycemic control and macro- and microvascular
      reactivity in type 2 diabetic patients.
AB  - To determine the effects of continuous aerobic exercise training (CON) vs
      interval aerobic exercise training (INT) on glycemic control and endothelium
      dependent vasodilatation, 43 participants with type 2 diabetes were randomly
      allocated to the sedentary, CON, and INT groups. The CON and INT exercise
      training programs were designed to yield the same energy expenditure/exercise
      session and included walking on treadmill for 30 and 40 min/day, 3 times/week for
      12 weeks. Body fatness and heart rate at rest decreased and leg muscle strength
      increased (all P < 0.05) in both the CON and INT groups. Fasting blood glucose
      levels decreased (P < 0.05) in both exercise groups but glycosylated hemoglobin
      levels decreased (P < 0.05) only in the INT group. Maximal aerobic capacity, flow
      mediated dilation, and cutaneous reactive hyperemia increased significantly in
      both exercise groups; however, the magnitude of improvements was greater in the
      INT group. Only the INT group experienced reductions in erythrocyte
      malondialdehyde and serum von Willebrand factor and increases in plasma
      glutathione peroxidase and nitric oxide (all P < 0.05). We concluded that both
      continuous and interval training were effective in improving glycemic control,
      aerobic fitness, and endothelium-dependent vasodilation, but the interval
      training program appears to confer greater improvements than the continuous
      training program.

PMID- 24102914
TI  - Accidental aspiration of foreign bodies in dental practice: clinical management
      and prevention.
AB  - OBJECTIVE: Foreign body aspiration is a possible complication of dental treatment
      that may result in a life-threatening situation. The foreign body is often
      spontaneously ejected from the airway, but in other cases, surgical intervention
      is needed. Prevention, diagnostic procedures, treatment and complications are
      discussed. MATERIALS AND METHODS: Three cases of aspiration of dental instruments
      are described: the piece was localised in the right main bronchus in two cases
      and in the left main bronchus in one case. RESULTS: All three cases underwent
      surgery (resection and bronchoscopy); in one case, the surgical attempt failed,
      and the foreign body was not located by radiography; it was assumed to have been
      expelled spontaneously. CONCLUSION: The management of dental materials and
      instruments requires particular care, especially if the patient is supine or semi
      recumbent. The dentist must be able to manage emergency situations in which
      patients accidentally inspire or swallow dental instruments or materials during
      treatment. Preventive techniques must be put in place because these incidents are
      preventable if the correct precautions are taken.

PMID- 24102915
TI  - The Consumer Quality Index in an accident and emergency department: internal
      consistency, validity and discriminative capacity.
AB  - BACKGROUND: Patients' experiences are an indicator of health-care performance in
      the accident and emergency department (A&E). The Consumer Quality Index for the
      Accident and Emergency department (CQI A&E), a questionnaire to assess the
      quality of care as experienced by patients, was investigated. The internal
      consistency, construct validity and discriminative capacity of the questionnaire
      were examined. METHODS: In the Netherlands, twenty-one A&Es participated in a
      cross-sectional survey, covering 4883 patients. The questionnaire consisted of 78
      questions. Principal components analysis determined underlying domains. Internal
      consistency was determined by Cronbach's alpha coefficients, construct validity
      by Pearson's correlation coefficients and the discriminative capacity by
      intraclass correlation coefficients and reliability of A&E-level mean scores (G
      coefficient). RESULTS: Seven quality domains emerged from the principal
      components analysis: information before treatment, timeliness, attitude of health
      care professionals, professionalism of received care, information during
      treatment, environment and facilities, and discharge management. Domains were
      internally consistent (range: 0.67-0.84). Five domains and the 'global quality
      rating' had the capacity to discriminate among A&Es (significant intraclass
      correlation coefficient). Four domains and the 'global quality rating' were close
      to or above the threshold for reliably demonstrating differences among A&Es. The
      patients' experiences score on the domain timeliness showed the largest range
      between the worst- and best-performing A&E. CONCLUSIONS: The CQI A&E is a
      validated survey to measure health-care performance in the A&E from patients'
      perspective. Five domains regarding quality of care aspects and the 'global
      quality rating' had the capacity to discriminate among A&Es.

PMID- 24102916
TI  - Nurse qualifications and perceptions of patient safety and quality of care in
      South Africa.
AB  - A plethora of research links professional nurses' qualifications to patient
      outcomes. Also, research has shown that reports by nurses on the quality of care
      correspond with process or outcome measures of quality in a hospital. New to the
      debate is whether professional nurses' qualifications impact on their perceptions
      of patient safety and quality of care. This research aims to investigate
      professional nurses' perceptions of patient safety and quality of care in South
      Africa, and the relationship between these perceptions and professional nurses'
      qualifications. A cross-sectional survey of 1117 professional nurses from medical
      and surgical units of 55 private and 7 public hospitals was conducted.
      Significant problems with regard to nurse-perceived patient safety and quality of
      care were identified, while adverse incidents in patients and professional nurses
      were underreported. Qualifications had no correlation with perceptions of patient
      safety and quality of care, although perceptions may serve as a valid indicator
      of patient outcomes. Creating an organizational culture that is committed to
      patient safety and encourages the sharing of adverse incidents will contribute to
      patient safety and quality of care in hospitals. 

PMID- 24102917
TI  - Left bundle branch block tachycardia in a case of dextrocardia: what is the
      mechanism?

PMID- 24102918
TI  - Triple-phase helical computed tomography in dogs with hepatic masses.
AB  - The purpose of this study was to determine the utility of triple-phase helical
      computed tomography (CT) for differentiating canine hepatic masses. Seventy dogs
      with hepatic masses underwent triple-phase CT followed by surgical removal of the
      hepatic masses. Triple-phase helical CT scans for each dog included precontrast,
      arterial phase, portal venous phase, and delayed phase studies. The removed
      hepatic masses were histopathologically classified as hepatocellular carcinoma (n
      = 47), nodular hyperplasia (n = 14), and hepatic metastatic tumors (n = 9) in
      dogs. Of the 47 hepatocellular carcinomas, the most common CT findings included a
      heterogeneous pattern with hyper-, iso-, and hypoenhancement in both the arterial
      and portal venous phases (40/47, 85.1%). Of the 14 nodular hyperplasias, the most
      common CT findings were a homogeneous pattern with hyper- and isoenhancement in
      both the portal venous and delayed phases (13/14, 92.9%). Of nine hepatic
      metastatic tumors, the most common CT findings included a homogeneous
      hypoenhancement pattern in both the arterial and portal venous phases (8/9,
      88.9%). In addition, 5 (55.6%) showed homogeneous hypoenhancement patterns in the
      delayed phase. Findings from our study indicated that triple-phase CT is a useful
      tool for preoperative differentiation of hepatocellular carcinoma, nodular
      hyperplasia, and hepatic metastatic tumors in dogs. 

PMID- 24102919
TI  - Type A aortic dissection with situs inversus.

PMID- 24102920
TI  - The putative Poc complex controls two distinct Pseudomonas aeruginosa polar
      motility mechanisms.
AB  - Each Pseudomonas aeruginosa cell localizes two types of motility structures, a
      single flagellum and one or two clusters of type IV pili, to the cell poles.
      Previous studies suggested that these motility structures arrive at the pole
      through distinct mechanisms. Here we performed a swimming motility screen to
      identify polar flagellum localization factors and discovered three genes
      homologous to the TonB/ExbB/ExbD complex that have defects in both flagella
      mediated swimming and pilus-mediated twitching motility. We found that deletion
      of tonB3, PA2983 or PA2982 led to non-polar localization of the flagellum and
      FlhF, which was thought to sit at the top of the flagellar localization
      hierarchy. Surprisingly, these mutants also exhibited pronounced changes in pilus
      formation or localization, indicating that these proteins may co-ordinate both
      the pilus and flagellum motility systems. Thus, we have renamed PA2983 and
      PA2982, pocA and pocB, respectively, for polar organelle co-ordinator to reflect
      this function. Our results suggest that TonB3, PocA and PocB may form a membrane
      associated complex, which we term the Poc complex. These proteins do not exhibit
      polar localization themselves, but are required for increased expression of pilus
      genes upon surface association, indicating that they regulate motility structures
      through either localization or transcriptional mechanisms. 

PMID- 24102921
TI  - Intraparenchymal leiomyoma of the male breast.

PMID- 24102922
TI  - Evaluation of a relapse-prevention program for methamphetamine-dependent inmates
      using a self-teaching workbook and group therapy.
AB  - AIM: The aim of this study was to evaluate the effect of a relapse-prevention
      program for methamphetamine (MAP)-dependent inmates in a prison. METHODS:
      Participants were 251 male inmates with MAP-abuse problems. We compared scores on
      the Self-efficacy Scale for Drug Dependence (SSDD) and the Stages of Change
      Readiness and Treatment Eagerness Scale (SOCRATES) before and after intervention
      with a self-teaching workbook and group therapy. RESULTS: For all participants,
      only SSDD scores increased during the pre-intervention period. SOCRATES-8D scores
      increased after the start of the intervention using the self-teaching workbook,
      and both SSDD and SOCRATES-8D scores increased when group therapy was
      implemented. Changes in scores in participants with moderate and high MAP
      dependence were considerably different from the scores of those with low
      dependence during the pre-intervention and the self-teaching workbook periods.
      CONCLUSION: Intervention using a self-teaching workbook and group therapy in
      prisons might be effective for inmates with more than moderate severity of MAP
      abuse.

PMID- 24102923
TI  - Positivity for islet cell autoantibodies in patients with monogenic diabetes is
      associated with later diabetes onset and higher HbA1c level.
AB  - AIMS: Islet cell autoantibodies are associated with autoimmune insulitis and
      belong to the diagnostic criteria of type 1 diabetes mellitus. However, growing
      evidence suggests that autoantibodies are present in other types of diabetes.
      Here, we focus on the autoantibody incidence in Czech patients with maturity
      onset diabetes of the young and analyse their functional relevance in terms of
      diabetes onset and control. METHODS: Autoantibodies against glutamic acid
      decarboxylase (GAD) 65 and protein tyrosine phosphatase islet antigen 2 (IA-2)
      were measured in a cohort of 28 Czech patients with maturity-onset diabetes of
      the young, all confirmed by genetic testing. Selected clinical data were
      correlated to the status and kinetics of autoantibodies. RESULTS: One quarter of
      patients with maturity-onset diabetes of the young examined (7/28; 25%) was
      positive for GAD or IA-2 autoantibodies. GAD autoantibodies were more prevalent
      (7/7) than IA-2 autoantibodies (1/7). The incidence of autoantibodies did not
      correlate with human leukocyte antigen status. The patients who were positive for
      the autoantibodies developed diabetes later than those who were autoantibody
      negative, but had worse glycaemic control (increased HbA1c ). Expression of
      autoantibodies decreased with any improvement of diabetes compensation. Only one
      patient did not correspond to the above and displayed signs of combined signs of
      maturity-onset diabetes of the young and Type 1 diabetes. CONCLUSIONS: The data
      suggest transient but highly prevalent islet cell autoantibody expression in
      Czech patients with maturity-onset diabetes of the young. The autoantibodies were
      found in patients with delayed diabetes onset, and in times of insufficient
      diabetes control. As improvement of glycaemic control was associated with a
      decrease in levels of autoantibodies, their presence may reflect the kinetics of
      beta-cell destruction induced by causes other than autoimmune ones.

PMID- 24102924
TI  - Nursing practice in stroke rehabilitation: systematic review and meta
      ethnography.
AB  - AIMS AND OBJECTIVES: To identify and synthesise the available research evidence
      in order to generate an explanatory framework for nursing practice in stroke
      rehabilitation. BACKGROUND: Although nurses are the largest professional group
      working with stroke survivors, there is limited understanding of nursing practice
      in stroke units. In particular, there is currently very little evidence in
      respect of nurses' involvement in poststroke rehabilitation. DESIGN: Meta
      ethnography. METHOD: A systematic review was undertaken. The review question was:
      'What is the nature of nursing practice in the care and rehabilitation of
      inpatient stroke survivors?' Searches of 12 electronic databases identified
      14,655 publications, and after screening, 778 remained; 137 papers were obtained
      and 54 retained for mapping. Sixteen qualitative studies were included in the
      meta-ethnography. RESULTS: Nurses' involvement in poststroke rehabilitation was
      limited. Contextual factors impacted on nurses' perceptions and practice. Nurses'
      integration of rehabilitation skills was perceived to be contingent on adequate
      nurse staffing levels and management of demands on nurses' time. Team working
      practices and use of the built environment indicated separation of nursing and
      therapy work. Physical care and monitoring were prioritised. Stroke-specific
      education and training was evident, but not consistent in content or approach.
      Stroke survivors and families needed help to understand nurses' role in
      rehabilitation. CONCLUSION: The review provides compelling evidence that there is
      an need to re-examine the role of nurses in contributing to poststroke
      rehabilitation, including clarifying when this process can safely begin and
      specifying the techniques that can be integrated in nurses' practice. RELEVANCE
      TO CLINICAL PRACTICE: Integrating stroke-specific rehabilitation skills in
      nurses' practice could contribute substantially to improving outcomes for stroke
      survivors. The explanatory framework developed from the review findings
      identifies issues which will need to be addressed in order to maximise nurses'
      contribution to the rehabilitation of stroke survivors.

PMID- 24102925
TI  - Maternal liver damage delays meiotic resumption in bovine oocytes through
      impairment of signalling cascades originated from low p38MAPK activity in cumulus
      cells.
AB  - The main objective of the present study is to investigate the molecular mechanism
      underlying the delay in progression of nuclear maturation in oocytes derived from
      cows with damaged livers (DL cows), which was previously reported. In present
      study, delayed progression of nuclear maturation of oocytes derived from DL cows
      relative to oocytes derived from cows with healthy livers (HL cows) was
      accompanied by low maturation promoting factor (MPF) activity (0.43 fold, p <
      0.05). When cumulus cells were removed from cumulus-oocyte complexes and the
      denuded oocytes were cultured, there was no difference in the progression of
      nuclear maturation between the two liver conditions. In addition, gap junctional
      communication (GJC) between the oocyte and cumulus cells was higher in DL cows
      than in HL cows at 3 and 7 h of in vitro maturation (IVM) (p < 0.05).
      Supplementation of IVM medium with epidermal growth factor (EGF) increased the
      ratio of germinal vesicle breakdown (GVBD) of oocytes derived from DL cows to the
      level seen in oocytes derived from HL cows. Additionally, the level of p38MAPK
      phosphorylation at 0 h of IVM was significantly lower in cumulus cells derived
      from DL cows than in cumulus cells derived from HL cows (HL cows, 53.5%; DL cows,
      28.9%; p < 0.05). Thus, a low level of p38MAPK phosphorylation in cumulus cells
      induced slow GJC closure between oocyte and cumulus cells, which resulted in slow
      meiotic maturation of oocytes derived from DL cows. 

PMID- 24102926
TI  - Mineral trioxide aggregate enhances the odonto/osteogenic capacity of stem cells
      from inflammatory dental pulps via NF-kappaB pathway.
AB  - OBJECTIVE: This study was designed to investigate the effects of mineral trioxide
      aggregate (MTA) on the osteo/odontogenic differentiation of inflammatory dental
      pulp stem cells (iDPSCs). MATERIALS AND METHODS: inflammatory DPSCs were isolated
      from the inflammatory pulps of rat incisors and cocultured with MTA-conditioned
      medium. MTT assay and flow cytometry were performed to evaluate the proliferation
      of iDPSCs. Alkaline phosphatase (ALP) activity, alizarin red staining, real-time
      RT-PCR, and Western blot assay were used to investigate the differentiation
      capacity as well as the involvement of NF-kappaB pathway in iDPSCs. RESULTS:
      Mineral trioxide aggregate-treated iDPSCs demonstrated the higher ALP activity
      and formed more mineralized nodules than the untreated group. The
      odonto/osteoblastic markers (Alp, Runx2/RUNX2, Osx/OSX, Ocn/OCN, and Dspp/DSP,
      respectively) in MTA-treated iDPSCs were significantly upregulated as compared
      with untreated iDPSCs. Mechanistically, cytoplastic phos-P65 and nuclear P65 in
      MTA-treated iDPSCs were significantly increased in a time-dependent manner.
      Moreover, the inhibition of NF-kappaB pathway suppressed the MTA-induced
      odonto/osteoblastic differentiation of iDPSCs, as indicated by decreased ALP
      levels, weakened mineralization capacity and downregulated levels of
      odonto/osteoblastic genes (Osx, Ocn, and Dspp). CONCLUSIONS: Mineral trioxide
      aggregate enhances the odonto/osteogenic capacity of DPSCs from inflammatory
      sites via activating the NF-kappaB pathway.

PMID- 24102927
TI  - Thailand conquered under-nutrition very successfully but has not slowed obesity.
AB  - Under-nutrition in Thailand has been successfully controlled for over two
      decades. However, Thailand is now facing a double-burden malnutrition problem
      where under- and over-nutrition coexist. Overweight, obesity, and related
      diseases are the main nutritional challenges, leading to high costs for curative
      care. Thailand foresees that nutrition can be an effective strategy for
      preventing diet-related non-communicable chronic diseases, and the country aims
      to reduce costs for secondary and tertiary health care. Various organizations
      have conducted national programmes, focusing especially on nutrition education
      and public campaigns, which have been sustainable and not sustainable. Only milk
      and certain foods for children are mandated for nutrition labeling. Guideline
      daily amounts is now the nutrient profile mandated for snack foods in Thailand.
      To increase efficiency, Thailand's National Food Committee has been established
      to link food, nutrition and health via a multi-sectoral approach. 

PMID- 24102928
TI  - A phase 2a, randomized, crossover trial of gabapentin enacarbil for the treatment
      of postherpetic neuralgia in gabapentin inadequate responders.
AB  - OBJECTIVE: To compare the efficacy of high-dose (3,600 mg/day) vs low-dose (1,200
      mg/day) oral gabapentin enacarbil (GEn) on pain intensity in adults with
      postherpetic neuralgia (PHN) and a history of inadequate response to >=1,800
      mg/day gabapentin. DESIGN: Multicenter, randomized, double-blind, crossover study
      (NCT00617461). SETTING: Thirty-five outpatient centers in Germany and the United
      States. SUBJECTS: Subjects aged >=18 years with a diagnosis of PHN. METHODS:
      During a 2-week baseline period, subjects received open-label treatment with
      1,800 mg/day gabapentin. Subjects who had a mean 24-hour average pain intensity
      score >=4 during the last 7 days of the baseline period were randomized to
      receive GEn (1,200 or 3,600 mg/day) for treatment period 1 (28 days), followed by
      GEn 2,400 mg/day (4 days), and the alternate GEn dose for treatment period 2 (28
      days). RESULTS: There was a modest but significant improvement in pain intensity
      scores with GEn 3,600 mg vs 1,200 mg (adjusted mean [90% confidence interval]
      treatment difference, -0.29 [-0.48 to -0.10]; P = 0.013). The difference in
      efficacy between doses was observed primarily in subjects who received the higher
      dose during treatment period 2; certain aspects of the study design may have
      contributed to this outcome. Plasma steady-state gabapentin exposure during GEn
      treatment was as expected and consistent between treatment periods. No new safety
      signals or adverse event trends relating to GEn exposure were identified.
      CONCLUSIONS: While the overall results demonstrated efficacy in a PHN population,
      the differences between treatment periods confound the interpretation. These
      findings could provide insight into future trial designs.

PMID- 24102929
TI  - Allogeneic hematopoietic stem cell transplantation for infants with idiopathic
      myelofibrosis.
AB  - IMF is a rare disease in children that can present during infancy and has a
      protracted course. The only known curative approach for this disease in adult
      patients is allogeneic HSCT. There are very few reports describing the long-term
      outcome of young children following stem cell transplantation for IMF. We report
      on eight patients less than two yr of age with IMF that did not resolve with
      supportive care measures. All patients underwent myeloablative conditioning
      regimen with busulfan and cyclophosphamide +/- ATG followed by HSCT from matched
      related (n = 6) or unrelated donor (n = 2). All patients achieved neutrophil and
      platelet engraftment. Four patients had grade II-III acute GVHD, and chronic GVHD
      developed in five patients (three mild and two severe). At a median follow-up of
      eight and a half yr (0.7-9), all patients are alive with complete resolution of
      their hematologic manifestations. At the last follow-up, all patients had normal
      endocrine function except for one patient who developed hypothyroidism. To date,
      this is the largest cohort of young children with IMF treated successfully with
      HSCT, with the longest duration of follow-up. In conclusion, our study showed
      that HSCT is a curative option for infants with IMF. 

PMID- 24102930
TI  - Unusual presentation of a granular cell astrocytoma.

PMID- 24102931
TI  - Reduction in harm from tracheostomy-related patient safety incidents following
      introduction of the National Tracheostomy Safety Project: our experience from two
      hundred and eighty-seven incidents.

PMID- 24102932
TI  - Microwave endometrial ablation at a frequency of 2.45 GHz for menorrhagia:
      analysis of treatment results at a single facility.
AB  - AIM: We aimed to evaluate the efficacy of microwave endometrial ablation at a
      frequency of 2.45 GHz in women with menorrhagia. This method has been attracting
      attention as an alternative to hysterectomy in the treatment of functional and
      organic menorrhagia. MATERIAL AND METHODS: We performed microwave endometrial
      ablation in 103 women with menorrhagia between August 2007 and October 2012. All
      patients had completed child bearing. We evaluated the efficacy of microwave
      endometrial ablation using a visual analog scale for menorrhagia, dysmenorrhea,
      and patient satisfaction. We also evaluated the incidence of hypermenorrhea
      recurrence, amenorrhea, and procedure complications in relation to patients'
      clinical factors, such as the presence of myoma, adenomyosis, uterine size, and
      type of bleeding. RESULTS: A total of 76 patients completed the evaluation
      period. Excessive menstruation improved from a preoperative mean visual analog
      score of 10, to 1.9 after treatment. Dysmenorrhea improved from a mean score of
      4.2, to 1.3, and patient satisfaction had a mean score of 9.0. Hemoglobin levels
      improved from 10.1 g/dL preoperatively to 12.5 g/dL postoperatively. Four
      patients experienced recurrence of excessive menstruation. No related clinical
      factors could be identified for recurrence risk or the occurrence of
      postoperative infection. A total of 26 patients (34.2%) became amenorrheic; these
      patients were less likely to have myomata, intramural myomata, and myomata larger
      than 5 cm. CONCLUSIONS: Microwave endometrial ablation at a frequency of 2.45 GHz
      is an effective and safe treatment. It should be considered as a standard
      treatment for conservative therapy-resistant menorrhagia.

PMID- 24102933
TI  - Consistency and completeness of reported outcomes in randomized trials of primary
      immunosuppression in kidney transplantation.
AB  - Inconsistent and incomplete outcome reporting may make estimates of treatment
      effects from published randomized trials unreliable. We aimed to determine
      outcome reporting practices and source of differences in reporting quality among
      randomized trials of primary immunosuppression in kidney transplantation. We
      searched the Cochrane Renal Group's Specialized Register, 2000-2012, specified
      four core outcomes we expected trials to report, and recorded if and how
      completely each was reported. We identified 179 trials. One hundred sixty-eight
      (94%) reported death, 145 (81%) as number dead and 119 (66%) as time to death.
      One hundred sixty-five (92%) reported graft loss, 158 (88%) as number with graft
      loss and 127 (71%) as time to graft loss. One hundred twenty-one (68%) reported
      creatinine and 114 (64%) estimated GFR (eGFR). One hundred forty-one (79%)
      provided complete reports of number dead, 95 (53%) censored and 99 (55%)
      uncensored number with graft loss. Seventy-three (41%) provided complete reports
      of time to death, 67 (37%) censored and 31 (17%) uncensored time to graft loss.
      Complete reporting of graft function was infrequent: 62 (35%) eGFR and 50 (28%)
      creatinine. All four outcomes were reported in any form in 61 (34%) and
      completely in 28 (16%) trials. No single trial or journal characteristic was
      consistently associated with complete outcome reporting. Outcome reporting in
      kidney transplant trials is inconsistent and frequently incomplete, and published
      estimates of treatment effects may be unreliable. 

PMID- 24102934
TI  - Adaptations to changing speed, load, and gradient in human walking: cost of
      transport, optimal speed, and pendulum.
AB  - It has been observed that the optimal speed (OPT) of human walking is independent
      of load on level surfaces because of the unaltered trajectory of the center of
      mass and consequent conservation of the pendular mechanism. However, the role of
      the inverted pendulum mechanism that combines speed, load, and gradient during
      walking remains unknown. In the present study, 10 subjects walked on a treadmill,
      with and without loading (25% of the body mass), at different speeds and slopes
      (0%, +7%, and +15%). The three-dimensional motion and VO2 were simultaneously
      registered. The mechanical external and internal work and the cost of transport
      (C) changed with the speed and gradient, but the load only affected C. OPT
      decreased with increasing gradient, and the pendular mechanics (R) was modified
      mainly as a result of changes in speed and gradient. OPT and R were independent
      of the load in these gradients. Remarkably, R increased with increasing speed and
      decreased (to 30%) with an increasing gradient; moreover, R was independent of
      load. Therefore, the energy-saving strategy by the pendular mechanism persists,
      although at a diminished level, in loaded walking on gradients and partially
      explains the OPT in this condition.

PMID- 24102935
TI  - Ultrasonographic characteristics of lipiduria in clinically normal cats.
AB  - Echoes are frequently seen in the urinary bladder of cats during abdominal
      ultrasound. These have been attributed to hematuria, pyuria, crystalluria, and
      lipid. However, sonographic findings have not been previously correlated with
      urinalysis. We prospectively evaluated 40 clinically normal cats via ultrasound,
      serum chemistry, and urinalysis. Thin layer chromatography was performed on the
      urine to determine the amount (mg) of lipid subfractions including
      diacylglycerol, triglyceride, phospholipid, free fatty acid, cholesterol, and
      cholesterol ester. Ninety percent (36/40) of the cats in our population had
      sonographic echoes suspended in the urinary bladder, with most having a
      subjective score of mild echoes (n = 20). None of the sonographic echoes were
      gravity dependent or caused distal acoustic shadowing, reverberation, or twinkle
      artifact. Of the cats with sonographic echoes in the urine, 66% (24/36) had no
      significant findings on urinalysis other than the presence of lipid. The total
      amount of subjective sonographic echoes was not significantly related to the
      total amount of fat measured on thin layer chromatography or the number of lipid
      droplets seen on urinalysis. An increased amount of urine diacylglycerol was
      significantly associated with clumping of echoes (P = 0.02) and the amount of
      lipid droplets seen on urinalysis (P = 0.04). An association between increased
      amounts of urine diacylglycerol and the amount of echoes seen on ultrasound
      approached significance (P = 0.05). Findings from this study support previously
      published theories that sonographic echoes within the urinary bladder of
      clinically normal cats may be due to urine lipid. 

PMID- 24102936
TI  - Can research development bursaries for patient and public involvement have a
      positive impact on grant applications? A UK-based, small-scale service
      evaluation.
AB  - BACKGROUND: Increasingly, research grant awarding bodies are regarding
      involvement at all stages of research, including prior to funding, as good
      practice. However, it is unclear how researchers should pay for this. Therefore,
      a pre-funding bursary scheme was designed. Up to L500 could be requested for
      involvement to develop a grant application for which user involvement is a key
      requisite for the funding body concerned. As the bursary scheme had run for 2
      years, an evaluation was conducted to ascertain whether the scheme was effective
      for incorporating early involvement and in developing the grant proposal.
      RESULTS: Twelve applications were made of which all were funded. The mean amount
      requested was L432.91; with the mean amount awarded L308.72. The involvement
      activities conducted all used qualitative methodology. Feedback regarding the
      bursaries was positive: enabling refinement of the research question and design;
      developing dialogue between the service users and the researchers; and helping
      with team building, with service users sometimes becoming co-applicants or
      members of the steering groups. The bursaries provided a learning opportunity -
      about involvement for the researchers and about research for the service users.
      The ultimate aim of the scheme was to enhance the research grant. Regarding this,
      the involvement paid for by the bursary meant that applicants could complete the
      involvement sections with in-depth information and clarity. CONCLUSION: For a
      relatively small financial outlay, appropriate involvement was made possible at
      an important part of the research process which is usually neglected due to lack
      of funding. Recommendations for implementation made.

PMID- 24102937
TI  - Extinction and recolonization of maritime Antarctica in the limpet Nacella
      concinna (Strebel, 1908) during the last glacial cycle: toward a model of
      Quaternary biogeography in shallow Antarctic invertebrates.
AB  - Quaternary glaciations in Antarctica drastically modified geographical ranges and
      population sizes of marine benthic invertebrates and thus affected the amount and
      distribution of intraspecific genetic variation. Here, we present new genetic
      information in the Antarctic limpet Nacella concinna, a dominant Antarctic
      benthic species along shallow ice-free rocky ecosystems. We examined the patterns
      of genetic diversity and structure in this broadcast spawner along maritime
      Antarctica and from the peri-Antarctic island of South Georgia. Genetic analyses
      showed that N. concinna represents a single panmictic unit in maritime Antarctic.
      Low levels of genetic diversity characterized this population; its median-joining
      haplotype network revealed a typical star-like topology with a short genealogy
      and a dominant haplotype broadly distributed. As previously reported with nuclear
      markers, we detected significant genetic differentiation between South Georgia
      Island and maritime Antarctica populations. Higher levels of genetic diversity, a
      more expanded genealogy and the presence of more private haplotypes support the
      hypothesis of glacial persistence in this peri-Antarctic island. Bayesian Skyline
      plot and mismatch distribution analyses recognized an older demographic history
      in South Georgia. Approximate Bayesian computations did not support the
      persistence of N. concinna along maritime Antarctica during the last glacial
      period, but indicated the resilience of the species in peri-Antarctic refugia
      (South Georgia Island). We proposed a model of Quaternary Biogeography for
      Antarctic marine benthic invertebrates with shallow and narrow bathymetric ranges
      including (i) extinction of maritime Antarctic populations during glacial
      periods; (ii) persistence of populations in peri-Antarctic refugia; and (iii)
      recolonization of maritime Antarctica following the deglaciation process. 

PMID- 24102938
TI  - Benefits and limits of anticholinergic use in schizophrenia: focusing on its
      effect on cognitive function.
AB  - All currently available antipsychotic drugs are the dopamine D2 receptor
      antagonists and are capable of producing extrapyramidal side-effects (EPS).
      Anticholinergic drugs are primarily used to treat EPS or prevent EPS induced by
      antipsychotics in the treatment of psychosis and schizophrenia. However, they can
      cause a variety of distressing peripheral side-effects (e.g. dry mouth, urinary
      disturbances, and constipation) and central adverse effects (e.g. cognitive
      impairment, worsening of tardive dyskinesia, and delirium). Disturbances in
      cognitive abilities are cardinal features of schizophrenia from its earliest
      phases and account for much of the functional disability associated with the
      illness. It is likely that long-term concomitant administration of
      anticholinergics exacerbates the underlying cognitive impairment in patients with
      schizophrenia and subsequently affects patients' quality of life. Thus, current
      treatment guidelines for schizophrenia generally do not recommend the
      prophylactic and long-term use of anticholinergics. However, the high use of long
      term anticholinergic drugs with antipsychotics has been identified as an
      important issue in the treatment of schizophrenia in several countries. To assess
      the benefits and limits of anticholinergic use in psychosis and schizophrenia,
      this article will provide a brief review of the pharmacology and clinical
      profiles of anticholinergic drugs and will focus on their effects on cognitive
      function in schizophrenia, particularly during the course of the early phase of
      the illness. In addition, we will address the effects of discontinuation of
      anticholinergics on cognitive function in patients with schizophrenia and provide
      a strategy for adjunctive anticholinergic use in patients treated with long
      acting injectable antipsychotics. 

PMID- 24102939
TI  - The association between dietary patterns and type 2 diabetes: a systematic review
      and meta-analysis of cohort studies.
AB  - BACKGROUND: Observational studies suggest that dietary pattern intake plays an
      important role in the development of type 2 diabetes. A meta-analysis was
      performed of existing cohort studies on the association between dietary patterns
      and the risk of type 2 diabetes. METHODS: Pertinent studies were identified by
      searching MEDLINE, EMBASE, Cumulative Index to Nursing and Allied Health
      Literature, PROQUEST, MEDNAR and the Joanna Briggs Institute Library of
      Systematic Reviews, as well as the reference lists of all identified studies up
      to September 2012. A random-effects meta-analysis was performed to pool relative
      risk (RR) estimates from individual studies to assess the relationship between
      dietary pattern intake and the risk of type 2 diabetes. Statistical heterogeneity
      was assessed using I(2) and sensitivity analyses were conducted. Publication bias
      was evaluated by visual inspection of funnel plots and was formally assessed
      using Egger's test. RESULTS: There were fifteen cohort studies that met the
      inclusion criteria. There was evidence of a reduction in the risk of type 2
      diabetes in the highest adherence compared to the lowest adherence to healthy
      dietary patterns [RR = 0.79, 95% confidence interval (CI) = 0.74-0.86, P <
      0.005]. An increase in the risk of type 2 diabetes was evident for the highest
      adherence compared to the lowest adherence to unhealthy dietary patterns (RR =
      1.44, 95% CI = 1.33-1.57, P < 0.005). CONCLUSIONS: The results of this systematic
      review and meta-analysis indicate that dietary patterns may be associated with
      the risk of type 2 diabetes.

PMID- 24102940
TI  - Epidemiology of Helicobacter pylori in Bhutan: the role of environment and
      Geographic location.
AB  - BACKGROUND: Bhutan is small mountainous country bordering India and China and
      consists of four geographic regions, west, east, central, and south. The
      epidemiology of Helicobacter pylori infection and risk factors associated with in
      Bhutan are not previously studied. The World Health Organization reported the
      incidence of stomach cancer to be very high in Bhutan. AIM: We conducted a cross
      sectional study to determine the seroepidemiologic pattern of H. pylori among
      Bhutanese from the four regions with emphasis on water source and household
      sanitation. METHODS: Between June and November 2012, blood samples from patients
      with complaints of dyspepsia were collected after obtaining an informed consent.
      Demographic information, occupation, family size living in the same household,
      consumption of betel nut, and aspects of household environment including type of
      latrines, source of drinking water were collected. All serum samples were tested
      for H. pylori immunoglobulin G (IgG) by enzyme-linked immunosorbent assay (ELISA)
      using MAGIWELL ELISA kit from United Biotech, USA. RESULTS: Two hundred and forty
      four patients between 17 and 75 years of age participated in the study, of them,
      102 were men, and the mean age was 38 (+/-14.2) years. The overall prevalence of
      H. pylori among patients was 86% with no difference between men and women (90 vs
      83%, respectively, p = .12). The prevalence was almost identical among all age
      groups: 81% at 17-20, 84% at 20-29, 93% at 30-39, 82% at 40-49, 87% at 50-59, and
      82% at >=60 years (p = .51). H. pylori prevalence was lower in the southern
      region of Bhutan (78%) compared with the central region (97%) (OR = 8.6; 95% CI =
      1.1-55; p = .02), eastern region (91%) (OR = 2.7; 95% CI = 1.1-7.2, p = .004) or
      the western region (83%) (OR = 1.4, 95% CI = 0.8-3.1, p = .07). The prevalence of
      H. pylori was significantly lower among household with less than 4 persons living
      in the same household. Source of drinking water, type of occupation, type of
      latrines, or consumption of betel nut showed no association with H. pylori
      prevalence. Logistic regression analysis revealed that residing region was the
      only significant variable. CONCLUSIONS: The high prevalence of antibodies to H.
      pylori among patients and in all groups could contribute to the high incident
      rate of gastric cancer in Bhutan. Crowded living condition and the residing
      region contribute to the variation of the prevalence of the infection. The lowest
      prevalence in southern part of the country could be due to the difference in the
      ethnicity as most of its population is of Indian and Nepal origin. Further data
      regarding H. pylori in Bhutan are critical to developing surveillance and
      prevention strategies for gastric cancer.

PMID- 24102941
TI  - Adverse reactions to equine-derived F(ab')2 -antivenin in 54 dogs envenomated by
      Vipera berus berus.
AB  - OBJECTIVE: To describe the occurrence of acute and delayed adverse reactions
      following the administration of an equine-derived F(ab')2 -antivenin in dogs with
      Vipera berus berus envenomation. DESIGN: Prospective study (2006-2009). SETTING:
      Private small animal clinics and university small animal teaching hospital in
      Norway. ANIMALS: Fifty-four dogs with Vipera berus berus envenomation treated
      with F(ab')2 -antivenin. INTERVENTIONS: Administration of equine-derived
      antivenin for treatment of Vipera berus berus envenomation in dogs. MEASUREMENTS
      AND MAIN RESULTS: Acute adverse reactions to antivenin administration occurred in
      4/54 dogs (7%), and facial swelling occurred in 2/54 dogs (4%), sudden
      respiratory distress in 1 dog, and vomiting occurred in 1 dog. The adverse
      reactions were self-limiting in 3 of the dogs, while 1 dog was treated with
      corticosteroids to reduce the facial swelling that occurred during administration
      of antivenin. No delayed adverse reactions believed to be associated with the
      antivenin administration were noted. CONCLUSIONS: An occurrence of adverse
      effects comparable to the numbers reported in human medicine (10%) should be
      expected when administering F(ab')2 -antivenin to dogs with Vipera berus berus
      envenomation. The results are also comparable with rates of adverse effects
      reported with antivenin administration for crotalid-envenomated dogs. Further
      research is required to determine whether there is a relationship between adverse
      and the number of vials administered or repeated use in the same patient.

PMID- 24102942
TI  - Religious and spiritual beliefs, self-esteem, anxiety, and depression among
      nursing students.
AB  - Research of the role of religious belief and/or spirituality has been conducted
      on a wide range of health-related topics, across many disciplines, and in many
      countries. The purpose of this study was to determine the relationship between
      religious beliefs, self-esteem, anxiety, and depression in nursing students in
      Cyprus. One hundred and twenty-three nursing students were asked to complete a
      survey consisting of four self-report questionnaires (Beck Depression Inventory,
      State-Trait Anxiety Inventory, The Royal Free Interview for Religious and
      Spiritual Beliefs, and Rosenberg Self-esteem Scale). The lowest levels of
      depression were observed in the third and fourth study year. Normal self-esteem
      levels were found in the majority of the students (71.3%) and most of them
      perceived current stress at mild levels. No significant differences on the basis
      of sex were observed. The vast majority (98.2%) of the students stated a strong
      religious and/or a spiritual belief that was strongly positively correlated with
      increased self-esteem and negatively correlated with depression, current stress,
      and stress as personality trait.

PMID- 24102943
TI  - Clinical association between serum gamma-glutamyltransferase levels and the
      development of insulin resistance in Korean men: a 5-year follow-up study.
AB  - AIMS: In recent years, gamma-glutamyltransferase has emerged as a predictor of
      cardiovascular disease, Type 2 diabetes mellitus, the metabolic syndrome and
      hypertension. However, it is not yet certain whether gamma-glutamyltransferase is
      a predictor for insulin resistance. The aim of this study was to examine the
      longitudinal association between baseline gamma-glutamyltransferase level and the
      development of insulin resistance in Korean men. METHODS: We performed a
      prospective cohort study, involving 22 931 healthy Korean men without baseline
      insulin resistance (homeostasis model assessment of insulin resistance, HOMA-IR <
      2.7) for 5 years. We checked the HOMA-IR serially to monitor the development of
      insulin resistance (incidence of HOMA-IR >= 2.7). A Cox proportional hazards
      model was used to determine hazard ratios for insulin resistance by quartile
      groups of baseline serum gamma-glutamyltransferase levels. RESULTS: During 81
      208.6 person-years of follow-up, 3856 (16.8%) cases of insulin resistance
      developed between 2006 and 2010. After adjusting for multiple covariates,
      including baseline HOMA-IR, the hazard ratios (95% CI) for incident insulin
      resistance comparing the second to the fourth quartile of baseline serum gamma
      glutamyltransferase levels with the first quartile were 1.19 (1.06-1.33), 1.38
      (1.23-1.53) and 1.58 (1.41-1.77), respectively (P for trend < 0.001).
      CONCLUSIONS: Our findings show that serum gamma-glutamyltransferase level could
      be a predictor of the development of insulin resistance in Korean men.

PMID- 24102944
TI  - Patch augmentation for tricuspid valve tethering.

PMID- 24102945
TI  - The Registry Evaluating Functional Outcomes of Resynchronization Management
      (REFORM): quality of life and psychological functioning in patients receiving
      cardiac resynchronization therapy.
AB  - BACKGROUND: Cardiac resynchronization therapy (CRT) is a treatment for heart
      failure (HF) that improves cardiac, functional, and quality of life (QoL)
      outcomes. This study was designed to examine the effect of the addition of CRT
      (CRTD) to the implantable cardioverter defibrillator (ICD) on psychological
      functioning. METHODS AND RESULTS: Overall, 99 participants completed batteries
      before and 9 months after ICD or CRTD implantation in a registry of HF patients
      receiving device treatment in 3 US centers. Measures included validated indices
      of mental health (State Trait Anxiety Inventory, Patient Health Questionnaire:
      Depression) and generic and disease/device-specific QoL (Medical Outcomes Study
      Short Form-12, Kansas City Cardiomyopathy Questionnaire, Florida Patient
      Acceptance Survey, Florida Shock Anxiety Scale). Mixed between-within analyses of
      covariance were employed to compare device groups on each outcome controlling for
      cardiac and demographic covariates. Clinically significant anxiety was elevated
      in both groups at both time points (57% CRTD at baseline, 29% CRTD 9 months, 44%
      ICD at baseline, 45% ICD 9 months). Clinically significant depressive symptoms
      were high at baseline (38% CRTD, 31% ICD), but dropped at follow-up (16% CRTD, 7%
      ICD; P = 0.01). Participants with CRTD had improved mental component and disease
      specific QoL following CRT; however, CRTD patients had worse QoL, worse mental
      component QoL at baseline, and worse device acceptance at 9-month follow-up than
      patients with ICDs (all P < 0.05). CONCLUSIONS: Evidence of low QoL,
      psychological functioning, and device acceptance provides the impetus to increase
      research on well-being of HF patients being implanted with CRTD in research and
      clinical work.

PMID- 24102946
TI  - Silicified virus-like nanoparticles in an extreme thermal environment:
      implications for the preservation of viruses in the geological record.
AB  - Biofilms that grow around Gumingquan hot spring (T = 71  degrees C, pH = 9.2) in
      the Rehai geothermal area, Tengchong, China, are formed of various cyanobacteria,
      Firmicutes, Aquificae, Thermodesulfobacteria, Desulfurococcales, and
      Thermoproteales. Silicified virus-like nanoparticles, 40-200 nm in diameter, are
      common inside the microbial cells and the extracellular polymeric substances
      around the cells. These nanoparticles, which are formed of a core encased by a
      silica cortex, are morphologically akin to known viruses and directly comparable
      to silicified virus-like particles that were produced in biofilms cultured in the
      laboratory. The information obtained from examination of the natural and
      laboratory-produced samples suggests that viruses can be preserved by
      silicification, especially while they are still encased in their host cells.
      These results expand our views of virus-host mineral interaction in extreme
      thermal environments and imply that viruses can be potentially preserved and
      identified in the geological record. 

PMID- 24102947
TI  - Host genetic susceptibility to oral cancer: evidence from meta-analyses and
      pooled analyses.
AB  - BACKGROUND: A large number of meta-analyses and pooled analyses have been
      published on the topic of the genetic variants for oral cancer, and many positive
      results have been identified; however, there might be some false-positive
      results. The aim of this study was to identify the 'true positive' (noteworthy)
      results using the method of false-positive report probability (FPRP). METHODS:
      The PubMed database, Embase database, CNKI database, and Wanfang database were
      searched to retrieve the meta-analyses, pooled analyses, and genome-wide
      association studies (GWAS), which addressed the associations between genetic
      polymorphisms and the risk of oral cancer. The significant associations were
      further analyzed using the method of FPRP. RESULTS: A total of 14 variants were
      identified from meta-analyses and pooled analyses, which concern the associations
      between oral cancer and genetic variants. Among these 14 variants, 9 variants
      were reported to be significantly associated with the risk of oral cancer (CYP1A1
      MspI, CYP2E1-RsaI/PstI, MTHFR-C677T, p73-G4C14-to-A4T14, XRCC1-Arg194Trp, CYP1A1
      Ile462Val, GSTM1-+/-, and NAT2 slow vs rapid). After assessing the results of
      FPRP, none of the nine statistically significant associations were noteworthy
      (true positive). In addition, no noteworthy results were identified from GWAS.
      CONCLUSIONS: In summary, this study found no noteworthy associations between
      variants and the risk of oral cancer. Further candidate genes associations
      studies should be performed to explore the etiology of oral cancer.

PMID- 24102948
TI  - Infiltrating Foxp3(+) regulatory T cells from spontaneously tolerant kidney
      allografts demonstrate donor-specific tolerance.
AB  - Foxp3(+) regulatory T cells (Tregs) have an essential role in immune and
      allograft tolerance. However, in both kidney and liver transplantation in humans,
      FOXP3(+) Tregs have been associated with clinical rejection. Therefore, the role
      and function of graft infiltrating Tregs have been of great interest. In the
      studies outlined, we demonstrated that Foxp3(+) Tregs were expanded in tolerant
      kidney allografts and in draining lymph nodes in the DBA/2 (H-2(d) ) to C57BL/6
      (H-2(b) ) mouse spontaneous kidney allograft tolerance model. Kidney allograft
      tolerance was abrogated after deletion of Foxp3(+) Tregs in DEpletion of
      REGulatory T cells (DEREG) mice. Kidney allograft infiltrating Foxp3(+) Tregs (K
      Tregs) expressed elevated levels of TGF-beta, IL-10, interferon gamma (IFN
      gamma), the transcriptional repressor B lymphocyte-induced maturation protein-1
      (Blimp-1) and chemokine receptor 3 (Cxcr3). These K-Tregs had the capacity to
      transfer dominant tolerance and demonstrate donor alloantigen-specific tolerance
      to skin allografts. This study demonstrated the crucial role, potency and
      specificity of graft infiltrating Foxp3(+) Tregs in the maintenance of
      spontaneously induced kidney allograft tolerance. 

PMID- 24102949
TI  - Computed tomographic characteristics of odontogenic neoplasms in dogs.
AB  - Odontogenic neoplasms are locally invasive oral tumors in dogs. The purpose of
      this retrospective study was to describe CT characteristics for varying
      histopathologic types of canine odontogenic neoplasms. A board-certified
      veterinary radiologist who was unaware of histologic findings reviewed and scored
      imaging studies. A total of 29 dogs were included in the study. Twenty-three of
      these dogs had concurrent dental radiographs. The most common CT characteristics
      for all tumor types were a direct association with or in the region of multiple
      teeth in 96.4% (27/28), contrast enhancement in 96.3% (26/27), alveolar bone
      lysis in 93.1% (27/29), and mass-associated tooth displacement in 85.2% (23/27).
      Mass-associated cyst-like structures were identified in 53.6% (15/28) and were
      only present in tumors containing odontogenic epithelium. Canine acanthomatous
      ameloblastomas (n = 15) appeared as extra-osseous (10/15) or intra-osseous (5/15)
      masses. Intra-osseous canine acanthomatous ameloblastomas were more likely to
      have mass-associated cyst-like structures and were subjectively more aggressive
      when compared with extra-osseous canine acanthomatous ameloblastomas. Amyloid
      producing odontogenic tumors (n = 3) had subjectively uniform CT imaging
      characteristics and consisted of round soft tissue and mineral attenuating masses
      with multiple associated cyst-like structures. Fibromatous epulides of
      periodontal ligament origin (n = 4) were contrast enhancing extra-osseous masses
      that were rarely referred for CT examinations and 25% (1/4) were not visible with
      CT. Other odontogenic tumors were less represented or had more variable CT
      imaging characteristics. Mass-associated tooth destruction was appreciated more
      often with dental radiographs and extra-oral tumor extension was identified more
      often with CT.

PMID- 24102950
TI  - Tumor-educated myeloid cells: impact the micro- and macroenvironment.
AB  - Immune escape mechanisms of cancers include some of the mechanisms normally used
      for immune homeostasis, particular those preventing autoimmunity; one of these is
      the polarisation of myeloid cells. Thereby, tumors, i.e. the cancerous and
      stromal cells, also condition distant sites like spleen and bone marrow via
      soluble factors and membrane vesicles such as exosomes in order to create a tumor
      educated macroenvironment. Albeit these mechanisms are currently in the focus of
      (tumor-)immunologic research, the first evidence had been published almost 40
      years ago. One of these early reports will be discussed here. 

PMID- 24102951
TI  - Obesity prevention and management: Singapore's experience.
AB  - Singapore's obesity prevalence among adult Singapore residents aged 18-69
      increased from 6.9% (2004) to 10.8% (2010). Among school-going children, the
      prevalence of overweight and severely overweight (body weight > 120% standard
      weight for height) increased from 1.4% (1976) to 12.7% (2006) for primary 1
      students, and 2.2% to 15.9% for primary 6 students. Fundamentally, obesity is a
      function of excess energy intake (food consumption) and insufficient energy
      expenditure (physical activity). In 2010, about 40% did not have sufficient
      physical activity, and about 60% consumed excess energy. For students in the
      mainstream schools, only a fifth consumed at least two servings of fruits and
      vegetables every day, and a tenth were physically active for at least 60 min on 5
      or more days a week. From a public health perspective, the most powerful levers
      for influencing population health lie in interventions that make healthy living
      convenient and an unconscious choice by targeting the social and environmental
      context. Recognizing this, the Health Promotion Board has in recent years made a
      strategic shift away from just public education campaigns aimed at individual
      behaviours, to focus on creating a ground-up social movement to enable and
      empower individuals to live out a healthy lifestyle.

PMID- 24102952
TI  - Distinguishing adrenal cortical carcinomas and adenomas: a study of
      clinicopathological features and biomarkers.
AB  - AIMS: To determine clinicopathological criteria and molecular markers helpful in
      distinguishing adrenocortical carcinomas (ACCs) from adrenocortical adenomas
      (ACAs). METHODS AND RESULTS: We analysed retrospectively the clinical and
      pathological features of 50 adrenal cortical tumours, and tested the expression
      of miR483-3p by in-situ hybridization as well as the expression of IGF2 and Smad4
      by immunohistochemistry. We found that tumour size, tumour weight, hormonal
      function and the Weiss system are all high-efficacy criteria for differentiating
      malignant from benign tumours (P < 0.001). MiR483-3p was overexpressed in 68% (17
      of 25) of ACCs compared to 12% (three of 25) of ACAs (P < 0.05). Using a
      combination of miR483-3p and Smad4 improved diagnostic accuracy. Molecular
      markers were then tested in an independent set of 15 borderline tumours. We
      confirmed that the combined use of miR483-3p and Smad4 immunochemistry can
      complement the Weiss score in the diagnosis of ACC in cases that display
      borderline histology. CONCLUSIONS: Tumour size, tumour weight, hormonal function
      and the Weiss system are useful clinicopathological criteria that can result in
      accurate diagnosis of most ACCs and ACAs. In challenging cases, miR483-3p and
      Smad4 expression may help in distinguishing these two entities.

PMID- 24102953
TI  - Role of immunological factors in the pathophysiology and diagnosis of bipolar
      disorder: comparison with schizophrenia.
AB  - Several lines of evidence point to the key role of neurobiological mechanisms and
      shared genetic background in schizophrenia and bipolar disorder. For both
      disorders, neurodevelopmental and neurodegenerative processes have been
      postulated to be relevant for the pathogenesis as well as dysregulation of immuno
      inflammatory pathways. Inflammation is a complex biological response to harmful
      stimuli and it is mediated by cytokines cascades, cellular immune responses,
      oxidative factors and hormone regulation. Cytokines, in particular, are supposed
      to play a critical role in infectious and inflammatory processes, mediating the
      cross-talk between the brain and the immune system; they also possibly contribute
      to the development of the central nervous system. From this perspective, even
      though mixed results have been reported, it seems that both schizophrenia and
      bipolar disorder are associated with an imbalance in inflammatory cytokines; in
      fact, some of these could represent biological markers of illness and could be
      possible targets for pharmacological treatments. In light of these
      considerations, the purpose of the present paper was to provide a comprehensive
      and critical review of the existing literature about immunological abnormalities
      in bipolar disorder with particular attention to the similarities and differences
      with schizophrenia. 

PMID- 24102954
TI  - The effects of sacral nerve stimulation on continence are temporarily maintained
      after turning the stimulator off.
AB  - AIM: Sacral nerve stimulation is an effective treatment for urinary and faecal
      incontinence even though its mechanism of action is uncertain. Central nervous
      system involvement by 'setting-up' neurological mechanisms appointed to control
      pelvic function has been hypothesized. The study aimed to evaluate whether the
      effects of long-term sacral nerve stimulation are memorized and therefore
      maintained after switching off the stimulator. METHOD: Patients having sacral
      nerve stimulation for faecal and/or urinary incontinence for at least 1 year had
      the stimulator turned off and the results monitored. Data recorded with the
      stimulator off were compared with post-implant data. If symptoms recurred the
      stimulator was switched back on. Nineteen patients entered the study. Fourteen
      had faecal and/or urinary incontinence and five had faecal incontinence alone.
      The symptoms were assessed by means of a bowel function diary and dedicated
      questionnaire. RESULTS: In 10 patients symptoms recurred at different intervals
      after a median off period of 3.4 months with a probability of symptom relapse of
      55%. The Fecal Incontinence Quality of Life (FIQL) score did not show any
      significant difference in nine patients with the stimulator off for at least 1
      year. No factors predictive of symptom recurrence were identified although an
      idiopathic aetiology, severity of disease and urinary incontinence had higher
      hazard ratios. During the off period, none of the scores and episodes of
      incontinence showed significant changes compared with the on period. CONCLUSION:
      The effects of sacral nerve stimulation on faecal and urinary incontinence were
      maintained in about half of patients after switching the stimulator off, but in
      some symptoms returned after different periods of time. The data shed new light
      on possible effects of sacral nerve stimulation on brain neuroplasticity in the
      control of continence.

PMID- 24102955
TI  - Treatment for glossopharyngeal neuralgia with peripheral glycerol injection: our
      experience in twenty-one older patients.

PMID- 24102957
TI  - Prediction of parturition in bitches utilizing continuous vaginal temperature
      measurement.
AB  - The objective of this study was to determine sensitivity and specificity of a
      body temperature decline in bitches to predict parturition. Temperature loggers
      were placed into the vaginal cavity of 16 pregnant bitches on day 56-61 after
      estimated ovulation or first mating. This measurement technique has been
      validated previously and enabled continuous sampling of body temperature. The
      temperature loggers were expelled from the vagina before delivery of the first
      pup. The computed values for specificity (77-92%) were higher than sensitivity
      (53-69%), indicating a more precise prognosis of parturition not occurring. In
      conclusion, our findings may assist interpreting vaginal temperature measurements
      in order to predict parturition in bitches. 

PMID- 24102956
TI  - Whole-genome sequencing of two North American Drosophila melanogaster populations
      reveals genetic differentiation and positive selection.
AB  - The prevailing demographic model for Drosophila melanogaster suggests that the
      colonization of North America occurred very recently from a subset of European
      flies that rapidly expanded across the continent. This model implies a sudden
      population growth and range expansion consistent with very low or no population
      subdivision. As flies adapt to new environments, local adaptation events may be
      expected. To describe demographic and selective events during North American
      colonization, we have generated a data set of 35 individual whole-genome
      sequences from inbred lines of D. melanogaster from a west coast US population
      (Winters, California, USA) and compared them with a public genome data set from
      Raleigh (Raleigh, North Carolina, USA). We analysed nuclear and mitochondrial
      genomes and described levels of variation and divergence within and between these
      two North American D. melanogaster populations. Both populations exhibit negative
      values of Tajima's D across the genome, a common signature of demographic
      expansion. We also detected a low but significant level of genome-wide
      differentiation between the two populations, as well as multiple allele surfing
      events, which can be the result of gene drift in local subpopulations on the edge
      of an expansion wave. In contrast to this genome-wide pattern, we uncovered a 50
      kilobase segment in chromosome arm 3L that showed all the hallmarks of a soft
      selective sweep in both populations. A comparison of allele frequencies within
      this divergent region among six populations from three continents allowed us to
      cluster these populations in two differentiated groups, providing evidence for
      the action of natural selection on a global scale.

PMID- 24102958
TI  - Recurrence of ovarian endometrioma after laparoscopic excision: risk factors and
      prevention.
AB  - AIM: The aim of this study was to assess the cut-off age of the risk factors for
      postoperative recurrence of ovarian endometriomas and to evaluate the end-points
      of follow-up after laparoscopic excision of ovarian endometriomas. MATERIAL AND
      METHODS: We retrospectively reviewed 167 patients who underwent laparoscopic
      excision of ovarian endometriomas at our hospital between 2000 and 2009, and
      followed up the patients until 2010. Following surgery, patients chose to receive
      gonadotrophin-releasing hormone agonist, oral contraceptive pills (OCP),
      dienogest, or no medication and underwent regular ultrasonographic examinations.
      Potential risk factors for recurrence, including age at surgery, were assessed in
      the patients receiving no medication. Postoperative recurrence, defined as re
      appearance of an ovarian endometrioma > 2 cm in size, was assessed for each
      treatment group. RESULTS: Age at surgery was the only significant risk factor for
      recurrence, at a cut-off of 32 years, obtained through receiver-operator curve
      analysis. In patients not receiving medication, the recurrence rate gradually
      increased up to 50% over 5 years; there was no recurrence 5 years after surgery.
      Although no recurrence was seen in patients during continuous treatment with OCP
      or dienogest, the disease recurred in 55.5% of patients after discontinuing OCP.
      CONCLUSIONS: Although adjuvant therapy for all patients may represent
      overtreatment, the findings of the present study suggest that, in the interest of
      fertility preservation, continuous postoperative hormonal treatment should be
      administered, at least to patients younger than 32 years. In patients who decline
      hormonal treatment, we recommend that they undergo follow-up for recurrence until
      5 years after surgery.

PMID- 24102959
TI  - Challenges of implementing collaborative models of decision making with trans
      identified patients.
AB  - BACKGROUND: Factors health providers face during the doctor-patient encounter
      both impede and assist the development of collaborative models of treatment.
      OBJECTIVE: I investigated decision making among medical and therapeutic
      professionals who work with trans-identified patients to understand factors that
      might impede or facilitate the adoption of the collaborative decision-making
      model in their clinical work. DESIGN: Following a grounded theory approach, I
      collected and analysed data from semi-structured interviews with 10 U.S.
      physicians and 10 U.S. mental health professionals. RESULTS: Doctors and
      therapists often desire collaboration with their patients but experience dilemmas
      in treating the trans-identified patients. Dilemmas include lack of formal
      education, little to no institutional support and inconsistent understanding and
      application of the main documents used by professionals treating trans-patients.
      CONCLUSIONS: Providers face considerable risk in providing unconventional
      treatments due to the lack of institutional and academic support relating to the
      treatment for trans-people, and the varied interpretation and application of the
      diagnostic and treatment documents used in treating trans-people. To address this
      risk, the relationship with the patient becomes crucial. However, trust, a
      component required for collaboration, is thwarted when the patients feel obliged
      to present in ways aligned with these documents in order to receive desired
      treatments. When trust cannot be established, medical and mental health providers
      can and do delay or deny treatments, resulting in the imbalance of power between
      patient and provider. The documents created to assist in treatment actually
      thwart professional desire to work collaboratively with patients.

PMID- 24102960
TI  - Retrospective evaluation of hyperosmolar hyperglycemia in 66 dogs (1993-2008).
AB  - OBJECTIVES: To clinically characterize a large group of dogs with the
      hyperosmolar hyperglycemic state (HHS) and to determine whether 2 HHS subgroups,
      dogs with hyperosmolar ketonuric (HK) diabetes mellitus (DM) and dogs with
      hyperosmolar nonketonuric (HNK) DM were clinically different from one another.
      DESIGN: Retrospective study. Records of 1,250 diabetic dogs that were examined
      between January 1993 and July 2008 were reviewed in order to identify dogs with
      HHS. Inclusion required a calculated serum osmolality >=325 mOsm/kg, with or
      without ketonuria. SETTING: University teaching hospital. ANIMALS: Sixty-six dogs
      with HHS including 34 dogs with HK, 25 dogs with HNK, and 7 dogs with
      unclassified HHS. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: HHS was
      diagnosed in 5% of dogs with DM. HK and HNK dogs were similar to one another in
      regard to most historical, physical examination, and clinicopathologic variables
      as well as outcome. Sixty-two percent of dogs with HHS survived to discharge from
      the hospital. Poor outcome of HHS dogs was associated with abnormal mental status
      (P = 0.03) and a low venous pH (P = 0.045). Dogs with HK were significantly more
      likely to have acute pancreatitis (P = 0.046), higher body temperature (P =
      0.006), higher WBC count (P = 0.01), and a shorter duration of clinical signs (P
      = 0.02) compared to dogs with HNK. Dogs with HNK had significantly higher BUN and
      creatinine concentrations (P = 0.0002 and P = 0.008, respectively) and higher
      calculated osmolality (P = 0.001) compared to dogs with HK. CONCLUSIONS: HHS is a
      rare condition in which poor outcome is associated with abnormal mental status
      and low venous pH. Among dogs with HHS, the subgroup of dogs with HK has
      significantly more acute pancreatitis, shorter duration of clinical signs, and
      higher body temperature and WBC count compared to dogs with HNK, whereas dogs
      with HNK have more azotemia and higher calculated osmolality compared to dogs
      with HK.

PMID- 24102961
TI  - Donors' characteristics and impact on outcomes in pediatric heart transplant
      recipients.
AB  - Organ availability and acceptability limit pediatric HTx. What characteristics
      define an unacceptable or high-risk pediatric donor remains unclear. The purpose
      of this study was to characterize a large cohort of pediatric donors and
      determine the donor risk factors, including cumulative risk, that affect
      recipient survival. Data from the PHTS, a prospective multicenter study, were
      used to examine the impact of donor factors on the outcomes of patients listed
      <18 yr of age who received a HTx between 1993 and 2009. Donor data were available
      for 3149 of 3156 HTx (99.8%). Donor cause of death, need for inotropes, or CPR
      did not affect survival outcomes (p = 0.05). Ischemic time also did not have an
      impact on overall recipient survival; however, longer ischemic times negatively
      impacted one-yr post-transplant survival (p < 0.0001). There was no impact of
      cumulative risk factors on survival (p = 0.8). Although used in a minority of
      cases, hormonal therapy in the donor positively impacted survival (p = 0.03). In
      multivariate analysis, the only donor factor associated with decreased survival
      was smaller donor BSA, the other factors being related to the recipient
      characteristics. When analyzed by recipient age, there were no donor-related
      factors that affected survival for those who received a transplant at <6 months
      of age. Longer ischemic time (p < 0.0001) and greater age difference between the
      recipient and donor (p = 0.0098) were donor-related factors impacting early-phase
      survival for recipients who received a graft at >=10 yr of age. Factors perceived
      to define a marginal or high-risk pediatric heart donor including inotrope use,
      CPR and donor cause of death may have less impact on outcomes than previously
      thought. Longer ischemic times did impact one yr, but not overall survival, and
      this impact was much greater with older donors. Parameters for accepting a donor
      heart can potentially be expanded, especially in the infant age group, but strong
      consideration should always be given to the interaction between ischemic time and
      donor age. 

PMID- 24102963
TI  - Serum atrial natriuretic peptide level inversely associates with metabolic
      syndrome in older adults.
AB  - AIM: Atrial natriuretic peptide (ANP) is a potent lipolytic agent that acts in
      adipose tissue. Low levels of ANP might lead to reduced lipolysis and excessive
      weight gain, which could be one of the biological alterations that contribute to
      the development of obesity. The aim of the present study was to evaluate the
      relationship between metabolic syndrome and fasting serum ANP concentrations in
      older adults. METHODS: Fasting blood samples were obtained from 90 older adults.
      Metabolic syndrome and its components were defined using diagnostic criteria from
      the International Diabetes Federation. RESULTS: A total of 40 older adults
      (44.4%) had metabolic syndrome. Fasting ANP level was negatively correlated with
      metabolic syndrome (P = 0.015). Univariate linear regression analysis showed that
      high-density lipoprotein cholesterol (P < 0.001) was positively correlated with
      serum logANP levels, whereas waist circumference (P = 0.001) and body fat mass (P
      = 0.002) were negatively correlated with fasting serum logANP levels.
      Multivariate forward stepwise linear regression analysis of the significant
      variables showed that high-density lipoprotein cholesterol (beta = 0.419, R(2) =
      0.268, P < 0.001) and body fat mass (beta = -0.396, R(2) = 0.154, P = 0.002) were
      independent predictors of fasting serum logANP levels in geriatric persons.
      CONCLUSIONS: Serum ANP levels were reduced in geriatric persons affected by
      metabolic syndrome. Body fat mass and high-density lipoprotein cholesterol were
      independent predictors of fasting serum ANP levels in older adults.

PMID- 24102962
TI  - individual variation in sleep quality and duration is related to cerebral mu
      opioid receptor binding potential during tonic laboratory pain in healthy
      subjects.
AB  - OBJECTIVE: Although poor sleep is a consequence of pain, sleep disturbance
      reciprocally induces hyperalgesia and exacerbates clinical pain. Conceptual
      models of chronic pain implicate dysfunctional supraspinal pain processing
      mechanisms, mediated in part by endogenous opioid peptides. Our preliminary work
      indicates that sleep disruption impairs psychophysical measures of descending
      pain modulation, but few studies have investigated whether insufficient sleep may
      be associated with alterations in endogenous opioid systems. This preliminary,
      exploratory investigation sought to examine the relationship between sleep and
      functioning of the cerebral mu opioid system during the experience of pain in
      healthy participants. SUBJECTS AND DESIGN: Twelve healthy volunteers participated
      in a 90-minute positron emission tomography imaging scan using [11C]Carfentanil,
      a mu opioid receptors agonist. During the session, pain responses to a 10%
      topical capsaicin cream were continuously rated on a 0-100 scale. Participants
      also completed the Pittsburgh Sleep Quality Index (PSQI). RESULTS: Poor sleep
      quality (PSQI) was positively and significantly associated with greater binding
      potential (BP) in regions within the frontal lobes. In addition, sleep duration
      was negatively associated with BP in these areas as well as the temporal lobe and
      anterior cingulate. CONCLUSIONS: These findings suggest that poor sleep quality
      and short sleep duration are associated with endogenous opioid activity in these
      brain regions during the application of a noxious stimulus. Elucidating the role
      of the endogenous opioid system in mediating some of the associations between
      sleep and pain could significantly improve our understanding of the
      pathophysiology of chronic pain and might advance clinical practice by suggesting
      interventions that could buffer the adverse effects of poor sleep on pain.

PMID- 24102964
TI  - The impact of segmental volumetric changes on functional mitral regurgitation: a
      study using three-dimensional regional time-volume analysis combined with low
      dose dobutamine.
AB  - PURPOSE: Using transthoracic three-dimensional (3D) echo regional volume analysis
      combined with low-dose dobutamine to investigate the effects on regional volume,
      mitral configuration and functional mitral regurgitation (FMR). METHODS: Fifty
      six patients with ischemic cardiomyopathy (ICM) were included in this study. The
      effective regurgitant orifice area (EROA) of FMR secondary to ICM with depressed
      left ventricular ejection fraction was compared with mitral tenting area and
      coaptation height (CH) before and after low-dose dobutamine (10 MUg/kg per min).
      Using 3-DQ software we measured and calculated regional stroke-volumes (rSV), the
      ratio of the rSV to the whole left ventricular stroke volume (rgSVratio) in all
      17 segments and the average rgSVratio of 4 anterior-PM attached segments
      (rgSVratio-aver anter-PM), 4 posterior-PM attached segments (rgSVratio-aver post
      PM), 8 PMs attached segments (rgSVratio-aver PMs) and all 17 segments before and
      after dobutamine. RESULTS: Compared with the resting condition, the SVr and
      rgSVratio on the basal and mid segments of anterior, lateral, inferior, and
      posterior walls were increased after dobutamine infusion (P < 0.05). EROA at rest
      was associated with tenting area, CH and rgSVratio-aver of PMs and the reduction
      in EROA caused by dobutamine was associated with reductions in tenting area, CH
      and increases in rgSVratio-aver of PMs. Tenting area was associated with
      rgSVratio-aver of PMs and reduction caused by dobutamine was associated with
      increases in rgSVratio-aver of PMs. CONCLUSIONS: The FMR decreasing during low
      dose dobutamine is quantitatively associated with the regional LV volume change
      of attached PMs. Real time transthoracic three-dimensional echocardiography may
      provide a simple and noninvasive approach to assess regional LV time-volume
      characteristic during FMR.

PMID- 24102965
TI  - Accuracy assessment of catheter guidance technology in electrophysiology
      procedures: a comparison of a new 3D-based fluoroscopy navigation system to
      current electroanatomic mapping systems.
AB  - BACKGROUND: With increasing complexity in electrophysiology (EP) procedures, the
      use of electroanatomic mapping systems (EAMS) as a supplement to fluoroscopy has
      become common practice. This is the first study that evaluates spatial and point
      localization accuracy for 2 current EAMS, CARTO3((r)) (Biosense Webster, Diamond
      Bar, CA, USA) and EnSite Velocity((r)) (St. Jude Medical Inc., St. Paul, MN,
      USA), and for a novel overlay guidance (OG) software (Siemens AG, Forchheim,
      Germany) in a phantom experiment. METHODS AND RESULTS: A C-arm CT scan was
      performed on an acrylic phantom containing holes and location markers. Spatial
      accuracy was assessed for each system using distance measurements involving known
      markers inside the phantom and properly placed catheters. Anatomical maps of the
      phantom were acquired by each EAMS, whereas the 3D-based OG software superimposed
      an overlay image of the phantom, segmented from the C-arm CT data set, onto
      biplane fluoroscopy. Registration processes and landmark measurements
      quantitatively assessed the spatial accuracy of each technology with respect to
      the ground truth phantom. Point localization performance was 0.49 +/- 0.25 mm in
      OG, 0.46 +/- 0.17 mm in CARTO3((r)) and 0.79 +/- 0.83 mm in EnSite((r)) . The
      registration offset between virtual visualization and reality was 1.10 +/- 0.52
      mm in OG, 1.62 +/- 0.77 mm in CARTO3((r)) and 2.02 +/- 1.21 mm in EnSite((r)) .
      The offset to phantom C-arm CT landmark measurements was 0.30 +/- 0.26 mm in OG,
      0.24 +/- 0.21 mm in CARTO3((r)) and 1.32 +/- 0.98 mm in EnSite((r)) .
      CONCLUSIONS: Each of the evaluated EP guidance systems showed a high level of
      accuracy; the observed offsets between the virtual 3D visualization and the real
      phantom were below a clinically relevant threshold of 3 mm.

PMID- 24102966
TI  - The evolution of policy and actions to tackle obesity in England.
AB  - Tackling obesity has been a policy priority in England for more than 20 years.
      Two formal government strategies on obesity in 2008 and 2011 drew together a
      range of actions and developed new initiatives to fill perceived gaps. Today, a
      wide range of policies are in place, including support for breastfeeding and
      healthy weaning practices, nutritional standards in schools, restrictions on
      marketing foods high in fat, sugar and salt to children, schemes to boost
      participation in sport, active travel plans, and weight management services. Data
      from annual surveys show that the rate of increase in obesity has attenuated in
      recent years, but has not yet been reversed. This paper considers the actions
      taken and what is known about the impact of individual policies and the
      overarching strategy to tackle obesity in England. 

PMID- 24102967
TI  - Redo sternotomy and cardiopulmonary bypass to repair a right ventricular
      penetrating injury.

PMID- 24102968
TI  - The interference of ethanol with heroin-stimulated psychomotor activation in mice
      is not related to changed brain concentrations of the active metabolites 6MAM or
      morphine.
AB  - It has been suggested that the potentiating effect observed in human beings when
      combining alcohol and heroin may be due to an interference of ethanol with the
      pharmacokinetics of heroin, leading to accumulation of the biologically active
      metabolites, 6-monoacetylmorphine (6MAM) and morphine. However, experimental
      evidence for this hypothesis is lacking. In this study, we used mice and examined
      the effect of ethanol on the metabolism of heroin by combining a locomotor
      activity test, which is a behaviour model representative of psychomotor
      stimulation, with pharmacokinetic studies in blood and brain tissue. Pre
      treatment with ethanol (1 and 2.5 g/kg, po) affected heroin-stimulated (2.5 and
      15 MUmol/kg, sc) locomotor activation significantly, resulting in a dose
      dependent reduction in run distance. However, the change in the activity profiles
      did not indicate any increase in the concentration of active metabolites.
      Pharmacokinetic studies in blood and brain supported the behavioural findings,
      showing no change in the time-versus-concentration curves of either 6MAM or
      morphine after administration of heroin (15 MUmol/kg, sc) to mice pre-treated
      with ethanol (2.5 g/kg, po). The concentration of heroin itself was elevated, but
      is probably of minor importance because heroin has low biological activity by
      itself. The in vivo pharmacokinetic findings were supported by experiments in
      vitro. In conclusion, studies in mice do not support the hypothesis from
      epidemiological studies of a pharmacokinetic interaction between alcohol and
      heroin.

PMID- 24102969
TI  - Computed tomographic characteristics of eosinophilic pulmonary granulomatosis in
      five dogs.
AB  - Canine pulmonary eosinophilic granulomatosis is a rare inflammatory pulmonary
      disease characterized by formation of eosinophilic granulomas that tend to
      obliterate the normal pulmonary architecture. The purpose of this retrospective
      study was to describe the CT characteristics of confirmed idiopathic pulmonary
      eosinophilic granulomatosis in a group of dogs. Five dogs met inclusion criteria.
      All patients were young adult dogs of variable breeds. No dog had concurrent
      occult heartworm disease. Computed tomographic characteristics most commonly
      included pulmonary masses and nodules of variable size, and lesions were most
      commonly located in the caudal lung lobes. Four dogs had large pulmonary masses
      with or without additional nodules and one dog had nodular lesions disseminated
      throughout the entire lung parenchyma. All large eosinophilic granulomas were
      smoothly margined, heterogeneous pulmonary masses displaying heterogeneous
      contrast enhancement. A honeycomb-like enhancement pattern was observed in all
      but one mass and consisted of multiple hyperattenuating rims delineating central
      hypoattenuating areas, suggestive of bronchiectatic lung with peripheral
      enhancing airway walls and fluid-filled, necrotic bronchial lumen. One dog had
      evidence of tracheobronchial lymphadenopathy. Findings indicated that canine
      eosinophilic pulmonary granulomatosis should be included as a differential
      diagnosis for dogs with CT characteristics of multiple pulmonary masses and/or
      nodules in caudal lung lobes, and a honeycomb-like enhancement pattern in masses
      after intravenous administration of iodinated contrast medium. 

PMID- 24102970
TI  - Comparison of the long-term outcome of two therapeutic strategies for the
      management of abdominal abscess complicating Crohn's disease: percutaneous
      drainage or immediate surgical treatment.
AB  - AIM: The management of abdominal abscesses complicating Crohn's disease is
      complex and involves a difficult choice between medical, radiological and
      surgical procedures. The long-term outcome was compared for two strategies for
      the management of abdominal abscess: percutaneous drainage (PD) followed by
      rescue surgery in the case of failure vs direct immediate surgery (IS). We also
      compared the results of IS with surgery performed after PD failure. METHODS: We
      retrospectively identified 44 patients with Crohn's disease with an abdominal
      abscess from January 2000 to December 2009. Therapeutic success was defined as
      abscess resolution and no reappearance within 1 year of follow-up. RESULTS: The
      first therapeutic approach was PD in 22 cases and IS in the other 22 cases. IS
      had a higher therapeutic success rate than PD (95.5% vs 27.2% respectively; P <
      0.001). PD was the only independent variable related to treatment failure in the
      multivariate analysis after adjustment for possible confounders such as abscess
      size, multilocularity, presence of fistula and corticosteroid use (OR 88.26, 95%
      CI 7.38-1055.36; P < 0.001). Surgery after failure of PD (n = 16) was associated
      with longer total hospitalization (56.12 +/- 35.89 vs 27.52 +/- 15.11 days; P =
      0.017) and longer postoperative stay (44.0 +/- 83.7 vs 14.3 +/- 30 days; P =
      0.179) and needed a second operation more often (5/16, 31% vs 1/22, 4.5%; P =
      0.065) than IS. CONCLUSIONS: Percutaneous drainage provided durable abscess
      resolution in only one-third of the patients compared with more than 90% of those
      treated with IS. In addition, surgery performed after PD failure results in a
      poorer outcome than IS.

PMID- 24102971
TI  - Psoriatic keratinocytes are resistant to tumor necrosis factor alpha's induction
      of mRNA for the NMDA-R2C subunit.
AB  - Psoriatic individuals demonstrate accelerated healing and the Koebner phenomenon,
      suggesting that psoriatic proliferation of keratinocytes is not inhibited
      appropriately after skin injury. Serial analysis of gene expression in TNFalpha
      exposed keratinocytes shows the greatest alteration in expression of NMDA-R2C.
      Expression of the NMDA receptor is altered in diseased skin containing TNFalpha,
      and TNFalpha plays a prominent role in psoriasis. An abnormality in induction of
      NMDA-R2C by TNFalpha in psoriatic keratinocytes may explain their lack of growth
      inhibition. We compared the capacity of TNFalpha to induce expression of NMDA-R2C
      in normal and psoriatic (involved and uninvolved) keratinocytes in vitro. After
      72 h of incubation with TNFalpha, normal keratinocytes demonstrated a significant
      induction of NMDA-R2C mRNA compared with control cultures, whereas psoriatic
      keratinocytes showed no induction. In an in vitro model of wounding (scratches on
      monolayers), TNFalpha inhibited migration/proliferation of keratinocytes only at
      the edge of NMDA-R2C expressing wounded monolayers of normal keratinocytes. 

PMID- 24102972
TI  - Changes in diet, cardiovascular risk factors and modelled cardiovascular risk
      following diagnosis of diabetes: 1-year results from the ADDITION-Cambridge trial
      cohort.
AB  - AIMS: To describe change in self-reported diet and plasma vitamin C, and to
      examine associations between change in diet and cardiovascular disease risk
      factors and modelled 10-year cardiovascular disease risk in the year following
      diagnosis of Type 2 diabetes. METHODS: Eight hundred and sixty-seven individuals
      with screen-detected diabetes underwent assessment of self-reported diet, plasma
      vitamin C, cardiovascular disease risk factors and modelled cardiovascular
      disease risk at baseline and 1 year (n = 736) in the ADDITION-Cambridge trial.
      Multivariable linear regression was used to quantify the association between
      change in diet and cardiovascular disease risk at 1 year, adjusting for change in
      physical activity and cardio-protective medication. RESULTS: Participants
      reported significant reductions in energy, fat and sodium intake, and increases
      in fruit, vegetable and fibre intake over 1 year. The reduction in energy was
      equivalent to an average-sized chocolate bar; the increase in fruit was equal to
      one plum per day. There was a small increase in plasma vitamin C levels.
      Increases in fruit intake and plasma vitamin C were associated with small
      reductions in anthropometric and metabolic risk factors. Increased vegetable
      intake was associated with an increase in BMI and waist circumference. Reductions
      in fat, energy and sodium intake were associated with reduction in HbA1c , waist
      circumference and total cholesterol/modelled cardiovascular disease risk,
      respectively. CONCLUSIONS: Improvements in dietary behaviour in this screen
      detected population were associated with small reductions in cardiovascular
      disease risk, independently of change in cardio-protective medication and
      physical activity. Dietary change may have a role to play in the reduction of
      cardiovascular disease risk following diagnosis of diabetes.

PMID- 24102974
TI  - Iron reduction and mineralization of deep-sea iron reducing bacterium Shewanella
      piezotolerans WP3 at elevated hydrostatic pressures.
AB  - In this study, iron reduction and concomitant biomineralization of a deep-sea
      iron reducing bacterium (IRB), Shewanella piezotolerans WP3, were systematically
      examined at different hydrostatic pressures (0.1, 5, 20, and 50 MPa). Our results
      indicate that bacterial iron reduction and induced biomineralization are
      influenced by hydrostatic pressure. Specifically, the iron reduction rate and
      extent consistently decreases with the increase in hydrostatic pressure. By
      extrapolation, the iron reduction rate should drop to zero by ~68 MPa, which
      suggests a possible shut-off of enzymatic iron reduction of WP3 at this pressure.
      Nano-sized superparamagnetic magnetite minerals are formed under all the
      experimental pressures; nevertheless, even as magnetite production decreases, the
      crystallinity and grain size of magnetite minerals increase at higher pressure.
      These results imply that IRB may play an important role in iron reduction,
      biomineralization, and biogeochemical cycling in deep-sea environments. 

PMID- 24102973
TI  - Protein kinase C regulates tonic GABA(A) receptor-mediated inhibition in the
      hippocampus and thalamus.
AB  - Tonic inhibition mediated by extrasynaptic GABA(A) receptors (GABA(A) Rs) is an
      important regulator of neuronal excitability. Phosphorylation by protein kinase C
      (PKC) provides a key mode of regulation for synaptic GABA(A) Rs underlying phasic
      inhibition; however, less attention has been focused on the plasticity of tonic
      inhibition and whether this can also be modulated by receptor phosphorylation. To
      address this issue, we used whole-cell patch clamp recording in acute murine
      brain slices at both room and physiological temperatures to examine the effects
      of PKC-mediated phosphorylation on tonic inhibition. Recordings from dentate
      gyrus granule cells in the hippocampus and dorsal lateral geniculate relay
      neurons in the thalamus demonstrated that PKC activation caused downregulation of
      tonic GABA(A) R-mediated inhibition. Conversely, inhibition of PKC resulted in an
      increase in tonic GABA(A) R activity. These findings were corroborated by
      experiments on human embryonic kidney 293 cells expressing recombinant
      alpha4beta2delta GABA(A) Rs, which represent a key extrasynaptic GABA(A) R
      isoform in the hippocampus and thalamus. Using bath application of low GABA
      concentrations to mimic activation by ambient neurotransmitter, we demonstrated a
      similar inhibition of receptor function following PKC activation at physiological
      temperature. Live cell imaging revealed that this was correlated with a loss of
      cell surface GABA(A) Rs. The inhibitory effects of PKC activation on
      alpha4beta2delta GABA(A) R activity appeared to be mediated by direct
      phosphorylation at a previously identified site on the beta2 subunit, serine 410.
      These results indicate that PKC-mediated phosphorylation can be an important
      physiological regulator of tonic GABA(A) R-mediated inhibition.

PMID- 24102975
TI  - The reasons behind variation in Gleason grading of prostatic biopsies: areas of
      agreement and misconception among 266 European pathologists.
AB  - AIMS: The Gleason scoring system underwent revision at the International Society
      of Urological Pathology (ISUP) conference in 2005. It is not known how
      uropathologists have interpreted its recommendations. METHOD AND RESULTS: A web
      based survey to European Network of Uropathology members received replies from
      266 pathologists in 22 countries. Eighty-nine per cent claimed to follow ISUP
      recommendations. Key areas of disagreement included the following. Smoothly
      rounded cribriform glands were assigned Gleason pattern (GP) 3 by 51% and GP 4 by
      49%. Necrosis was diagnosed as GP 5 by 62%. Any amount of secondary pattern of
      higher grade in needle biopsies was included in the Gleason score by 58%.
      Tertiary GP of higher grade on needle biopsies was included in the Gleason score
      by only 58%. If biopsy cores were embedded separately, only 56% would give a
      Gleason score for each core/slide examined; 68% would give a concluding Gleason
      score and the most common method was a global Gleason score (77%). Among those
      who blocked multiple biopsy cores together, 46% would only give an overall
      Gleason score for the case. CONCLUSION: Misinterpretation of ISUP 2005 is
      widespread, and may explain the variation in Gleason scoring seen. Clarity and
      uniformity in teaching ISUP 2005 recommendations is necessary.

PMID- 24102976
TI  - Predictors of implantable pulse generator placement after sacral neuromodulation:
      who does better?
AB  - OBJECTIVES: Numerous studies have documented a relationship between provider
      variables, including surgeon volume and specialty, and outcomes for surgical
      procedures. In this study we analyzed claims data from a Medicare database to
      analyze outcomes of sacral neuromodulation (SNM) with respect to both provider
      and patient factors. MATERIALS AND METHODS: A 5% random sample of Medicare
      beneficiaries from 1997 to 2007 was the data source. Data retrieved included
      demographic information, ICD-9 diagnosis codes, and CPT procedure codes.
      Multivariate analysis was performed to identify predictors of progression to
      implantable pulse generator (IPG) implantation. RESULTS: After stage I testing,
      urologists were more likely than gynecologists to proceed to IPG placement
      (Center for Medicare and Medicaid Services: 49% vs. 43%, p < 0.0001). After
      percutaneous testing, gynecologists were more likely than urologists to proceed
      to battery placement (63% vs.44%, p = 0.005). Among the patient variables
      analyzed, women were more likely than men to progress to battery placement.
      Patients treated by high-volume providers had higher rates of IPG placement after
      formal stage I trials (71% vs. 33%, p < 0.0001). CONCLUSIONS: The rate of IPG
      implantation after SNM was greater among high-volume providers. Women had better
      outcomes than men. Further research may better define the relationship between
      outcomes of sacral neuromodulation and specific etiology of voiding dysfunction.

PMID- 24102977
TI  - Review of neurophysiological findings in patients with schizophrenia.
AB  - Schizophrenia has been conceptualized as a failure of cognitive integration, and
      abnormalities in neural circuitry have been proposed as a basis for this
      disorder. In this article, we focus on electroencephalography and
      magnetoencephalography findings in patients with schizophrenia. Auditory-P50, 
      N100, and -P300 findings, visual-P100, -N170, and -N400 findings, and neural
      oscillations in patients with schizophrenia are overviewed. Published results
      suggest that patients with schizophrenia have neurophysiological deficits from
      the very early phase of sensory processing (i.e., P50, P100, N100) to the
      relatively late phase (i.e., P300, N400) in both auditory and visual perception.
      Exploring the associations between neural substrates, including neurotransmitter
      systems, and neurophysiological findings, will lead to a more comprehensive
      understanding of the pathophysiology of schizophrenia.

PMID- 24102978
TI  - Stress rapidly dysregulates the glutamatergic synapse in the prefrontal cortex of
      cocaine-withdrawn adolescent rats.
AB  - Although several lines of evidence have shown that chronic cocaine use is
      associated with stress system dysregulation, the underlying neurochemical
      mechanisms are still elusive. To investigate whether the rapid stress-induced
      response of the glutamatergic synapse was influenced by a previous history of
      cocaine, rats were exposed to repeated cocaine injections during adolescence
      [from postnatal day (PND) 28-42], subjected to a single swim stress (5 minutes)
      three days later (PND 45) and sacrificed 15 minutes after the end of this
      stressor. Critical determinants of glutamatergic homeostasis were measured in the
      medial prefrontal cortex (mPFC) whereas circulating corticosterone levels were
      measured in the plasma. Exposure to stress in saline-treated animals did not show
      changes in the crucial determinants of the glutamatergic synapse. Conversely, in
      cocaine-treated animals, stress dynamically altered the glutamatergic synapse by:
      (1) enhancing the presynaptic vesicular mediators of glutamate release; (2)
      reducing the transporters responsible for glutamate clearance; (3) increasing the
      postsynaptic responsiveness of the N-methyl-D-aspartate subunit GluN1; and (4)
      causing hyperresponsive spines as evidenced by increased activation of the
      postsynaptic cdc42-Pak pathway. These findings indicate that exposure to cocaine
      during adolescence sensitizes mPFC glutamatergic synapses to stress. It is
      suggested that changes in glutamatergic signaling may contribute to the increased
      sensitivity to stress observed in cocaine users. Moreover, glutamatergic
      processes may play an important role in stress-induced reinstatement of cocaine
      seeking. 

PMID- 24102979
TI  - Heterosubtypic cross-protection induced by whole inactivated influenza virus
      vaccine in mice: influence of the route of vaccine administration.
AB  - BACKGROUND: Development of influenza vaccines capable of inducing broad
      protection against different virus subtypes is necessary given the ever-changing
      viral genetic landscape. Previously, we showed that vaccination with whole
      inactivated virus (WIV) induces heterosubtypic protection against lethal virus
      infection in mice. Whole inactivated virus-induced cross-protection was found to
      be mediated primarily by flu-specific CD8+ T cells. OBJECTIVES: As it has been
      demonstrated that the route of vaccine administration strongly influences both
      the quantity and quality of vaccine-induced immunity, in this study, we
      determined which route of WIV administration induces optimal heterosubtypic cross
      protection. METHODS: We compared the magnitude of the immune response and
      heterosubtypic protection against lethal A/PR/8/34 (H1N1) infection after
      subcutaneous (SC), intramuscular (IM), and intranasal (IN) vaccination with
      A/NIBRG-14 (H5N1) WIV. RESULTS: Subcutaneous and IM administration was superior
      to IN administration of influenza WIV in terms of flu-specific CD8+ T-cell
      induction and protection of mice against lethal heterosubtypic challenge.
      Surprisingly, despite the very low flu-specific CD8+ T-cell responses detected in
      IN-vaccinated mice, these animals were partially protected, most likely due to
      cross-reactive IgA antibodies. CONCLUSION: The results of this study show that
      the magnitude of WIV-induced flu-specific CD8+ T-cell activity depends on the
      applied vaccination route. We conclude that parenteral administration of WIV
      vaccine, in particular IM injection, is superior to IN vaccine delivery for the
      induction of heterosubtypic cross-protection and generally appears to elicit
      stronger immune responses than mucosal vaccination with WIV.

PMID- 24102980
TI  - Unearthing carrion beetles' microbiome: characterization of bacterial and fungal
      hindgut communities across the Silphidae.
AB  - Carrion beetles (Coleoptera, Silphidae) are well known for their behaviour of
      exploiting vertebrate carcasses for nutrition. While species in the subfamily
      Silphinae feed on large carcasses and on larvae of competing scavengers, the
      Nicrophorinae are unique in monopolizing, burying and defending small carrion,
      and providing extensive biparental care. As a first step towards investigating
      whether microbial symbionts may aid in carcass utilization or defence, we
      characterized the microbial hindgut communities of six Nicrophorinae (Nicrophorus
      spp.) and two Silphinae species (Oiceoptoma noveboracense and Necrophila
      americana) by deep ribosomal RNA amplicon sequencing. Across all species,
      bacteria in the family Xanthomonadaceae, related to Ignatzschineriao larvae, were
      consistently common, and several other taxa were present in lower abundance
      (Enterobacteriales, Burkholderiales, Bacilli, Clostridiales and Bacteroidales).
      Additionally, the Nicrophorinae showed high numbers of unusual Clostridiales,
      while the Silphinae were characterized by Flavobacteriales and Rhizobiales
      (Bartonella sp.). In addition to the complex community of bacterial symbionts,
      each species of carrion beetle harboured a diversity of ascomycetous yeasts
      closely related to Yarrowia lipolytica. Despite the high degree of consistency in
      microbial communities across the Silphidae--specifically within the Nicrophorinae
      -both the fungal symbiont phylogeny and distance-based bacterial community
      clustering showed higher congruence with sampling locality than host phylogeny.
      Thus, despite the possibility for vertical transmission via anal secretions, the
      distinct hindgut microbiota of the Silphidae appears to be shaped by frequent
      horizontal exchange or environmental uptake of symbionts. The microbial community
      profiles, together with information on host ecology and the metabolic potential
      of related microorganisms, allow us to propose hypotheses on putative roles of
      the symbionts in carcass degradation, detoxification and defence.

PMID- 24102981
TI  - Risk of kidney stones with surgical intervention in living kidney donors.
AB  - A kidney stone in a person with a solitary kidney requires urgent attention,
      which may result in surgical and/or hospital attention. We conducted a matched
      retrospective cohort study to determine if living kidney donors compared to
      healthy nondonors have a higher risk of: (i) kidney stones with surgical
      intervention, and (ii) hospital encounters for kidney stones. We reviewed all
      predonation charts for living kidney donations from 1992 to 2009 at five major
      transplant centers in Ontario, Canada, and linked this information to healthcare
      databases. We selected nondonors from the healthiest segment of the general
      population and matched 10 nondonors to every donor. Of the 2019 donors and 20 190
      nondonors, none had evidence of kidney stones prior to cohort entry. Median
      follow-up time was 8.4 years (maximum 19.7 years; loss to follow-up <7%). There
      was no difference in the rate of kidney stones with surgical intervention in
      donors compared to nondonors (8.3 vs. 9.7 events/10 000 person-years; rate ratio
      0.85; 95% confidence interval [CI] 0.47-1.53). Similarly there was no difference
      in the rate of hospital encounters for kidney stones (12.1 vs. 16.1 events/10 000
      person-years; rate ratio 0.75; 95% CI 0.45-1.24). These interim results are
      reassuring for the safety of living kidney donation.

PMID- 24102983
TI  - Effect of Nigella sativa oil on postoperative peritoneal adhesion formation.
AB  - AIM: We aim to evaluate the effect of Nigella sativa oil (NSO) on postoperative
      peritoneal adhesion formation in female rats. This experimental study is the
      first on the prevention of postoperative adhesion formation by NSO. METHODS:
      Twenty-four Wistar albino female rats were randomly assigned to three groups of
      eight rats each. Rats in group 1 were each injected i.p. with 1 mL of NSO. In
      group 2, an adhesion model was created with no injection of NSO. In group 3, an
      adhesion model was created and the area was covered with 1 mL of NSO. The rats
      were killed on postoperative day 8, and the severity of adhesions was evaluated
      macroscopically and histopathologically. RESULTS: There was a statistically
      significant difference in adhesion scores between group 2 (control) and group 3
      (NSO-treated) (P = 0.003). Statistically significant differences in angiogenesis,
      fibrosis and inflammation were observed between the control and Nigella sativa
      groups (P = 0.002, P = 0.001 and P = 0.004, respectively). CONCLUSION: Covering
      peritoneal surfaces with NSO after peritoneal trauma is effective in decreasing
      peritoneal adhesion formation.

PMID- 24102984
TI  - The origin of amniotic polymorphonuclear leucocytes in the mare.
AB  - The objective of this study was to investigate the presence and origin of
      polymorphonuclear leucocytes (PMNLs) in the amniotic fluid of mares giving birth
      to healthy foals. Material from 25 mares was included. Amniotic fluid was
      collected during parturition before breakage of the amniotic vesicle. Manual
      microscopic cytologic evaluation was made on cytospin preparations after
      staining. PMNLs were found in all amniotic samples examined. The genomic DNA was
      extracted from 12 of the amniotic fluid samples and was genotyped. The results
      indicate that the PMNLs originate from the foetus. 

PMID- 24102982
TI  - G-protein coupled receptor 56 promotes myoblast fusion through serum response
      factor- and nuclear factor of activated T-cell-mediated signalling but is not
      essential for muscle development in vivo.
AB  - Mammalian muscle cell differentiation is a complex process of multiple steps for
      which many of the factors involved have not yet been defined. In a screen to
      identify the regulators of myogenic cell fusion, we found that the gene for G
      protein coupled receptor 56 (GPR56) was transiently up-regulated during the early
      fusion of human myoblasts. Human mutations in the gene for GPR56 cause the
      disease bilateral frontoparietal polymicrogyria; however, the consequences of
      receptor dysfunction on muscle development have not been explored. Using knockout
      mice, we defined the role of GPR56 in skeletal muscle. GPR56(-/-) myoblasts have
      decreased fusion and smaller myotube sizes in culture. In addition, a loss of
      GPR56 expression in muscle cells results in decreases or delays in the expression
      of myogenic differentiation 1, myogenin and nuclear factor of activated T-cell
      (NFAT)c2. Our data suggest that these abnormalities result from decreased GPR56
      mediated serum response element and NFAT signalling. Despite these changes, no
      overt differences in phenotype were identified in the muscle of GPR56 knockout
      mice, which presented only a mild but statistically significant elevation of
      serum creatine kinase compared to wild-type. In agreement with these findings,
      clinical data from 13 bilateral frontoparietal polymicrogyria patients revealed
      mild serum creatine kinase increase in only two patients. In summary, targeted
      disruption of GPR56 in mice results in myoblast abnormalities. The absence of a
      severe muscle phenotype in GPR56 knockout mice and human patients suggests that
      other factors may compensate for the lack of this G-protein coupled receptor
      during muscle development and that the motor delay observed in these patients is
      likely not a result of primary muscle abnormalities. 

PMID- 24102985
TI  - Multiple listing for pediatric heart transplantation: is one child's gain,
      another child's loss?

PMID- 24102986
TI  - Does health-related quality of life predict hospitalization or mortality in
      patients with atrial fibrillation?
AB  - BACKGROUND: Poor health-related quality of life (QOL) is related to morbidity and
      mortality in coronary heart disease and ventricular arrhythmias as well as to
      mortality in patients with heart failure (HF) and atrial fibrillation (AF). This
      study examined the contributions of QOL to the prediction of 1-year
      hospitalization and mortality in patients with AF, independent of HF. METHODS:
      This study used the public use dataset from the NHLBI/NIH AFFIRM randomized
      clinical trial. Patients enrolled in the QOL substudy (N = 693) were randomly
      assigned to rate or rhythm control. QOL was assessed with the Medical Outcomes
      Study 36-item Short Form Health Survey (SF-36) and the Quality of Life Index
      Cardiac Version (QLI-CV). Data were analyzed with logistic regression to predict
      1-year hospitalization and Cox proportional hazards analysis to predict
      mortality. RESULTS: In the first year of participation in the study 37% (n = 256)
      were hospitalized; mortality was 14.3% (n = 93) with mean follow-up of 3.5 years.
      Patients' mean age was 69.8 +/- 8.2 years, were largely male (62%), and white
      (93%). Patient histories included 70.8% hypertension, 38.2% coronary artery
      disease (CAD), and 23.7% HF. History of stroke, HF, rhythm control arm, lower SF
      36 mental component scores (MCS), and lower SF-36 physical component scores (PCS)
      predicted hospitalization (P < 0.001). Diabetes, female gender, older age, CAD,
      hypertension, and lower PCS predicted mortality (P < 0.001). CONCLUSION: QOL adds
      meaningful information beyond traditional biomedical factors to the prediction of
      mortality and/or hospitalization of patients with AF. Interventions for improving
      QOL and helping patients adapt to AF treatments may decrease hospitalization and
      improve survival.

PMID- 24102988
TI  - Multifocal right atrial myxoma with multiple pulmonary embolism.

PMID- 24102987
TI  - Regional anesthesia does not consistently block ischemic pain: two further cases
      and a review of the literature.
AB  - OBJECTIVE: Ischemic pain is complex and poorly understood. There is controversy
      regarding whether or not regional anesthetic techniques block ischemic pain. We
      present two further cases where regional anesthesia did not block ischemic pain
      despite adequate motor and sensory block. CASE REPORT 1: A 29-year-old healthy
      male underwent elective right lateral ankle ligament reconstruction for ankle
      instability with single-injection femoral and sciatic nerve blocks as the sole
      anesthetic. He reported no pain during or after surgery; approximately 90 min
      after the cast dressing was applied, he complained of severe pain in his medial
      ankle despite persistent complete sensory and motor blockade. The cast was
      removed, and he had immediate and complete resolution of his pain, which was
      thought to be due to ischemia. CASE REPORT 2: A 45-year-old female with a history
      of diabetes mellitus, hypertension, and 30 pack-year smoking history presented
      with increasingly cold, cyanotic, and painful fingers in her right hand. She
      suffered necrotic lesions of her 4th and 5th fingers accompanied by severe
      ischemic type pain. A continuous C7 cervical paravertebral block was placed.
      Despite dense sensory and motor blockade, she still reported excruciating pain
      that ultimately required amputation after developing demarcated gangrene.
      CONCLUSION: The two cases support the growing body of evidence that ischemic pain
      is largely unaffected by regional anesthesia, even with adequate sensory and
      motor block. The prevailing understanding regarding peripheral nerve blocks in
      patients in danger of developing compartment syndrome should be reconsidered.

PMID- 24102989
TI  - Innovative strategies targeting obesity and non-communicable diseases in South
      Africa: what can we learn from the private healthcare sector?
AB  - Over 50% of South African adult women and 30% of adult men are either overweight
      or obese, and nearly half of all adults are insufficiently active, with major
      increases in obesity-associated healthcare expenditures since 1980, a high
      proportion of which are paid by private health insurance. In this paper, we
      describe the Vitality programme, an incentivized health promotion programme from
      South Africa's largest private health insurer, Discovery Health, with over 2.5
      million beneficiaries. Wellness activities of the programme include health risk
      assessments, subsidized gym memberships and smoking cessation or weight loss
      programmes with many incentives, including cash back on purchases of healthy
      foods. This incentive-based programme has shown a significant relationship
      between levels of engagement in wellness activities, in particular increasing
      participation in fitness-related activities, with lower healthcare expenditure
      and an increase in the overall ratio of healthy foods to total food purchases.
      This programme demonstrates that incentives may reduce the barriers for entry
      into care, increase preventive screening and increase engagement in healthy
      behaviours for prevention and management of obesity. This 'carrots versus sticks'
      approach may have implications for public health policy even in lower- and middle
      income settings and underserved communities. 

PMID- 24102990
TI  - Abnormal agitated saline study results after tetralogy of Fallot repair.
AB  - Residual intracardiac or extracardiac shunting is frequently seen in patients
      with repaired congenital heart disease and can cause systemic hypoxemia. We
      present the case of an adult with tetralogy of Fallot who underwent two
      corrective surgical procedures as a child with subsequent pulmonary valve
      replacement due to residual pulmonary insufficiency. Further details of her
      operative history were otherwise unknown. After being lost to follow-up for many
      years, she presented with unexplained cyanosis and a markedly abnormal agitated
      saline study on transthoracic echocardiography in which only the left heart
      filled after contrast administration. We review the differential diagnosis for
      such a presentation and discuss the utility of cardiac magnetic resonance imaging
      (MRI) to define the etiology. Cardiac MRI, a frequently used imaging modality to
      longitudinally assess adult patients with congenital heart disease, provides
      excellent image quality of cardiac structures and the ability to perform
      angiography in a variety of imaging planes. These advantages render cardiac MRI,
      a useful modality to determine the etiology of unexplained cyanosis in these
      patients as both intracardiac and extracardiac shunts can be detected. 

PMID- 24102991
TI  - Parastomal hernia: treatment and prevention 2013; where do we go from here?

PMID- 24102992
TI  - Simultaneous pheochromocytoma and third-degree atrioventricular block in 2 dogs.
AB  - OBJECTIVE: To describe the occurrence of pheochromocytoma with third-degree
      atrioventricular (AV) block in 2 dogs. CASE SERIES SUMMARY: Two dogs were
      referred for echocardiograms and further diagnostic and therapeutic treatment for
      third-degree AV block. Abdominal ultrasound of 1 dog revealed an adrenal mass,
      while that of the other dog revealed bilateral adrenal masses. While undergoing
      treatment, 1 dog experienced cardiac arrest and could not be revived with
      cardiopulmonary resuscitation, and the other dog was humanely euthanized.
      Histological findings of the masses were consistent with pheochromocytomas. NEW
      OR UNIQUE INFORMATION PROVIDED: To the authors' knowledge, this is the first
      report with histologic evidence of pheochromocytoma and clinical presentation of
      third-degree AV block in dogs. In human literature, simultaneous presentation of
      both disease states is rare and has been infrequently reported.

PMID- 24102993
TI  - Colorectal adenocarcinoma cancer in New Zealand in those under 25 years of age
      (1997-2007).
AB  - INTRODUCTION: Colorectal cancer is common and primarily a disease of older
      people. Colorectal cancer in patients aged 25 years and under is infrequent and
      may represent a unique subgroup of patients. This study aimed to describe the
      population of young people in New Zealand diagnosed with colorectal cancer, their
      tumour characteristics, management and outcomes. METHODS: A retrospective
      clinical study was conducted via review of medical records for all patients 25
      years of age and under, diagnosed with colorectal adenocarcinoma in New Zealand
      between 1 January 1997 and 31 December 2007. RESULTS: Fifty patients with
      colorectal adenocarcinoma were identified from the New Zealand Cancer Registry.
      Seven had a positive family history of colorectal cancer, while eight had
      predisposing factors (hereditary nonpolyposis colorectal cancer, familial
      adenomatous polyposis, ulcerative colitis, Crohn's disease, regional enteritis).
      The most common presenting symptoms were abdominal pain and weight loss. Twenty
      eight cases presented acutely. Eighteen presented with stage IV disease at
      diagnosis. Eighteen were referred to a genetics service. Five-year overall
      survival was 49%. DISCUSSION: Those aged 25 years and under that develop
      colorectal cancer tend to present acutely and move through the secondary care
      pathway swiftly, being diagnosed at a more advanced stage, and have a poorer
      prognosis than their adult counterparts. Familial cancers form a more significant
      component of youth colorectal cancers compared to the older population and input
      from genetic service should be considered.

PMID- 24102994
TI  - Invited review--Off-site PET imaging programs: challenges and opportunities.
AB  - Veterinarians are gaining interest in and access to Position Emission Tomography
      (PET and PET/CT) imaging for both clinical and research applications. This
      manuscript provides an overview of how veterinarians may approach the use of off
      site PET and PET/CT scanners already in use for human medical imaging in order to
      gain access to this technology without direct investment in costly equipment and
      infrastructure. An overview of general procedures, animal transport, and
      radiation safety considerations is offered along with references to key
      regulatory statutes that may apply to the operation of PET imaging facilities in
      individual states. 

PMID- 24102995
TI  - Alterations in ethanol-induced accumbal transmission after acute and long-term
      zinc depletion.
AB  - Alcoholism is subject to extensive research, but the role of changes in
      metabolism caused by alcohol consumption has been poorly investigated. Zinc
      (Zn(2+) ) deficiency is a common metabolic aberration among alcoholics and Zn(2+)
      influences the function of ligand-gated ion channels, known pharmacological
      targets of ethanol (EtOH). Here, we investigate whether manipulation of
      extracellular levels of Zn(2+) modulates EtOH-induced increases of dopamine (DA)
      output, as measured by in vivo microdialysis in the rat, and whether voluntary
      EtOH consumption is altered by Zn(2+) deficiency. Our findings show that the
      Zn(2+) -chelating agent tricine slowly raises DA levels when perfused in the
      nucleus accumbens (nAc), whereas the more potent Zn(2+) chelator TPEN reduces DA
      levels. We also show that pre-treatment with either tricine or TPEN blocks the
      EtOH-induced DA elevation. Chronic Zn(2+) deficiency induced by a Zn(2+) -free
      diet did not affect EtOH consumption, but excitatory transmission, assessed by
      striatal field-potential recordings in the nAc shell, was significantly modulated
      both by Zn(2+) -free diet and by EtOH consumption, as compared with the EtOH
      naive controls. The present study indicates that Zn(2+) influences EtOH's
      interaction with the brain reward system, possibly by interfering with glycine
      receptor and GABAA receptor function. This also implies that Zn(2+) deficiency
      among alcoholics may be important to correct in order to normalize important
      aspects of brain function. 

PMID- 24102996
TI  - Nurse-sensitive indicators suitable to reflect nursing care quality: a review and
      discussion of issues.
AB  - AIMS AND OBJECTIVES: To review nurse-sensitive indicators that may be suitable to
      assess nursing care quality. BACKGROUND: Patient safety concerns, fiscal
      pressures and patient expectation create a demand that healthcare providers
      demonstrate the quality of nursing care delivered. As a result, nurse managers
      are increasingly encouraged to provide evidence of nursing care quality. Nurse
      sensitive indicators are being proposed as a means of meeting this need. DESIGN:
      Literature review. METHODS: A review of the literature was conducted using CINAHL
      and MEDLINE from 2002-2011. Key search terms were nurs* and sensitive indicators,
      outcome measures, indicators, metrics and patient outcomes. RESULTS: Most of the
      research has examined the relationship between nursing structural variables and
      patient outcomes in acute care settings and have explored potential indicators
      for specific patient groups and nursing roles. When using nurse-sensitive
      indicators, issues concerning the selection, reporting and sustained use are
      important for nurse managers to consider. CONCLUSION: Evidence for the nurse
      sensitivity of some commonly used indicators is inconsistent due to the disparity
      in definitions used, data collection and analysis methods. Further research on
      the application and implementation of these indicators is required to assist
      nurse managers in attempting to quantify the quality of nursing care. Nurses need
      to continue to strive to achieve agreement on the definitions of indicators,
      gather strong consistent evidence of nurse-sensitivity, resolve issues of regular
      data collection and consider selection, reporting and sustainment when
      implementing nurse-sensitive indicators. RELEVANCE TO CLINICAL PRACTICE: Once
      identified, nurse-sensitive indicators can be applied for quality improvement
      purposes, but consensus is required to fully realise their potential. Nurse
      managers need to be aware of the factors that can influence the use of indicators
      at unit level. Strategies need to be implemented to promote these indicators
      becoming integrated with routine nursing care.

PMID- 24102997
TI  - TRPA1: a transducer and amplifier of pain and inflammation.
AB  - The transient receptor potential ankyrin 1 (TRPA1) ion channel on peripheral
      terminals of nociceptive primary afferent nerve fibres contributes to the
      transduction of noxious stimuli to electrical signals, while on central endings
      in the spinal dorsal horn, it amplifies transmission to spinal interneurons and
      projection neurons. The centrally propagating nociceptive signal that is induced
      and amplified by TRPA1 not only elicits pain sensation but also contributes to
      peripheral neurogenic inflammation through a peripheral axon reflex or a
      centrally mediated back propagating dorsal root reflex that releases vasoactive
      agents from sensory neurons in the periphery. Endogenous TRPA1 agonists that are
      generated under various pathophysiological conditions both in the periphery and
      in the spinal cord have TRPA1-mediated pro-nociceptive and pro-inflammatory
      effects. Among endogenous TRPA1 agonists that have been shown to play a role in
      the pathogenesis of pain and inflammatory conditions are, for example,
      methylglyoxal, 4-hydroxynonenal, 12-lipoxygenase-derived hepoxilin A3, 5,6
      epoxyeicosatrienoic acid and reactive oxygen species, while mustard oil and
      cinnamaldehyde are most commonly used exogenous TRPA1 agonists in experimental
      studies. Among selective TRPA1 antagonists are HC-030031, A-967079, AP-14 and
      Chembridge-5861528. Recent evidence indicates that TRPA1 plays a role also in
      transition of acute to chronic pain. Due to its location on a subpopulation of
      pain-mediating primary afferent nerve fibres, blocking the TRPA1 channel is
      expected to have antinociceptive, antiallodynic and anti-inflammatory effects. 

PMID- 24102998
TI  - Characteristics of cardiac epithelium at the esophagogastric junction of a
      pediatric population with gastroesophageal reflux.
AB  - Cardiac mucosa (CM) of the adult, regardless its location, shares phenotypic
      characteristics with Barrett's epithelium, namely villin expression and a
      Barrett's pattern of cytokeratins 7 and 20 expression. As far as we know, the
      phenotypic profile of CM in children has not been studied. The objective was to
      evaluate the phenotypic profile of cardiac mucosa from the esophagogastric
      junction of children with reflux symptoms. Biopsies routinely performed at the
      esophagogastric junction of children submitted to upper-gastrointestinal
      endoscopy for complaints suggestive of reflux were retrieved from the archive and
      used for the purposes of this study. Biopsies were assessed for the presence of
      squamous epithelium, cardiac and oxyntic mucosa and intestinal metaplasia.
      Samples displaying both squamous and columnar epithelia were
      immunohistochemically evaluated for the presence of villin and sucrase-isomaltae
      and for the expression of cytokeratins 7 and 20. From the 42 biopsies samples
      retrieved, 30 had simultaneously squamous and columnar epithelia. Cardiac mucosa
      was present in 86.7% of the cases, and intestinal metaplasia was observed only in
      one (3.3%). Villin expression in cardiac mucosa was observed in 96% of the cases
      and a cytokeratins 7 and 20 Barrett's pattern in 73%. Sucrase-isomaltase and MUC2
      were only expressed in the case with intestinal metaplasia. Cardiac mucosa was
      high prevalent in biopsies from the esophagogastric junction of children with
      reflux. As in adults, cardiac mucosa in children has an immunoprofile similar to
      Barrett's esophagus. For the first time, it was shown that pediatric cardiac
      mucosa frequently expresses villin. 

PMID- 24102999
TI  - Increased pituitary volume in subjects at risk for psychosis and patients with
      first-episode schizophrenia.
AB  - AIM: Enlarged pituitary gland has been reported in schizophrenia, possibly
      reflecting hypothalamic-pituitary-adrenal hyperactivity. The aim of the present
      study was to examine whether individuals at risk of psychosis also have similar
      changes. METHODS: Magnetic resonance imaging was used to examine the pituitary
      volume in 22 individuals with at-risk mental state (ARMS; 11 male, 11 female), 64
      first-episode patients with schizophrenia (FESz; 37 male, 27 female), and 86
      healthy controls. The control subjects were divided into age- and gender-matched
      controls for ARMS (11 male, 11 female) and FESz (37 male, 27 female). RESULTS:
      Both the ARMS and FESz groups had a larger pituitary volume compared with matched
      controls, but no difference was found between the ARMS and FESz subjects. There
      was no association between the pituitary volume and clinical variables
      (symptommeasures at scanning, daily dosage or duration of antipsychotic
      medication) in either clinical group. The pituitary volume did not differ
      significantly between the ARMS individuals who later developed schizophrenia (n =
      5) and those who did not (n = 17). The pituitary volume was larger in women than
      in men for all diagnostic groups. CONCLUSION: The finding of increased pituitary
      volume in both ARMS and FESz subjects may reflect a common vulnerability to
      stress in early psychosis. Further work in a larger ARMS sample is required to
      examine the possible relationship between pituitary volume and emergence of
      psychosis.

PMID- 24103000
TI  - Analysis of cerebral toxoplasmosis in a series of 170 allogeneic hematopoietic
      stem cell transplant patients.
AB  - INTRODUCTION: Cerebral toxoplasmosis is a rare but fatal complication in
      hematopoietic stem cell transplant patients, which mostly is caused by
      reactivation of latent disease. METHODS: In this study, we report an analysis of
      cerebral toxoplasmosis in a series of 170 allogeneic stem cell transplant
      patients during a 30-month period at our institution. RESULTS: Among these
      allogeneic stem cell transplant patients, 5 were diagnosed with cerebral
      toxoplasmosis by brain magnetic resonance imaging and polymerase chain reaction
      of Toxoplasma gondii DNA. The incidence of cerebral toxoplasmosis was found to be
      2.94%. CONCLUSION: Mortality rate is known to be very high in cerebral
      toxoplasmosis; therefore, it is life saving to diagnose the disease in the early
      stages and start treatment promptly, especially in high-endemic countries like
      Turkey.

PMID- 24103001
TI  - RIPK3-mediated necroptosis promotes donor kidney inflammatory injury and reduces
      allograft survival.
AB  - Kidney transplant injury occurs with ischemia and alloimmunity. Members of the
      receptor interacting protein kinase family (RIPK1,3) are key regulators of
      "necroptosis," a newly recognized, regulated form of necrosis. Necroptosis and
      apoptosis death appear to be counterbalanced as caspase-8 inhibition can divert
      death from apoptosis to necrosis. Inhibition of necroptosis in donor organs to
      limit injury has not been studied in transplant models. In this study,
      necroptosis was triggered in caspase inhibited tubular epithelial cells (TEC)
      exposed to tumor necrosis factor alpha in vitro, while RIPK1 inhibition with
      necrostatin-1 or use of RIPK3(-/-) TEC, prevented necroptosis. In vivo, short
      hairpin RNA silencing of caspase-8 in donor B6 mouse kidneys increased
      necroptosis, enhanced high-mobility group box 1 release, reduced renal function
      and accelerated rejection when transplanted into BALB/c recipients. Using
      ethidium homodimer perfusion to assess necrosis in vivo, necrosis was abrogated
      in RIPK3(-/-) kidneys postischemia. Following transplantation, recipients
      receiving RIPK3(-/-) kidneys had longer survival (p = 0.002) and improved renal
      function (p = 0.03) when compared to controls. In summary, we show for the first
      time that RIPK3-mediated necroptosis in donor kidneys can promote inflammatory
      injury, and has a major impact on renal ischemia-reperfusion injury and
      transplant survival. We suggest inhibition of necroptosis in donor organs may
      similarly provide a major clinical benefit.

PMID- 24103002
TI  - Dihydroavenanthramide D prevents UV-irradiated generation of reactive oxygen
      species and expression of matrix metalloproteinase-1 and -3 in human dermal
      fibroblasts.
AB  - Ultraviolet B (UVB) radiation induces photoageing by upregulating the expression
      of matrix metalloproteinases (MMPs) in human skin cells. Dihydroavenanthramide D
      (DHAvD) is a synthetic analog to naturally occurring avenanthramide, which is the
      active component in oats. Although anti-inflammatory, anti-atherosclerotic and
      antioxidant effects have been reported, the antiphotoageing effects of DHAvD are
      yet to be understood. In this study, we investigated the inhibitory effects of
      DHAvD on UVB-induced production of reactive oxygen species (ROS) and expression
      of MMPs, and its molecular mechanism in UVB-irradiated human dermal fibroblasts.
      Western blot and real-time PCR analyses revealed that DHAvD inhibited UVB-induced
      MMP-1 and MMP-3 expression. It also significantly blocked UVB-induced ROS
      generation in fibroblasts. Additionally, DHAvD attenuated UVB-induced
      phosphorylation of MAPKs, activation of NF-kappaB and AP-1. DHAvD regulates UVB
      irradiated MMP expression by inhibiting ROS-mediated MAPK/NF-kappaB and AP-1
      activation. DHAvD may be a useful candidate for preventing UV light-induced skin
      photoageing. 

PMID- 24103003
TI  - Newborn transition.
AB  - The transition from intrauterine to extrauterine life is a complex adaptation.
      Although, in a sense, the entire time in utero is in preparation for this
      transition, there are many specific anatomic and physiologic changes that take
      place in the weeks and days leading up to labor that facilitate a healthy
      transition. Some, including increasing pulmonary vasculature and blood flow, are
      part of an ongoing process of maturation. Others, such as a reversal in the lung
      from secreting fluid to absorbing fluid and the secretion of pulmonary
      surfactant, are associated with the hormonal milieu that occurs when spontaneous
      labor is impending. Interventions such as elective cesarean birth or induction of
      labor may interfere with this preparation for birth. Postnatal interventions such
      as immediate clamping of the umbilical cord and oropharyngeal suction may also
      compromise the normal process of newborn transition. This article reviews the
      physiology of the fetal to newborn transition and explores interventions that may
      facilitate or hinder the optimal process. 

PMID- 24103004
TI  - Fifty-five years of enzyme classification: advances and difficulties.
AB  - Since the publication of a list of enzymes classified according to the reactions
      that they catalysed, by Dixon and Webb in 1958, its content and presentation have
      undergone a number of significant changes. These have been necessitated by new
      information, as well as the need to improve clarity. The move from printed
      versions to the online environment, through the ExplorEnz website, has allowed
      the process of adding newly reported enzymes to be automated and the information
      content to be enriched. Search and output facilities have also been enhanced.
      These and the problems attendant on the use of the Enzyme Commission
      classification system for some groups of enzymes are the subject of this review. 

PMID- 24103005
TI  - Massive invasion of exotic Barbus barbus and introgressive hybridization with
      endemic Barbus plebejus in Northern Italy: where, how and why?
AB  - Biological invasions and introgressive hybridization are major drivers for the
      decline of native freshwater fish. However, the magnitude of the problem across a
      native species range, the mechanisms shaping introgression as well as invader's
      dispersal and the relative role of biological invasions in the light of multiple
      environmental stressors are rarely described. Here, we report extensive (N = 665)
      mtDNA sequence and (N = 692) microsatellite genotypic data of 32 Northern
      Adriatic sites aimed to unravel the invasion of the European Barbus barbus in
      Italy and the hybridization and decline of the endemic B. plebejus. We highlight
      an exceptionally fast breakthrough of B. barbus within the Po River basin,
      leading to widespread introgressive hybridization with the endemic B. plebejus
      within few generations. In contrast, adjacent drainage systems are still
      unaffected from B. barbus invasion. We show that barriers to migration are
      inefficient to halt the invasion process and that propagule pressure, and not
      environmental quality, is the major driver responsible for B. barbus success.
      Both introgressive hybridization and invader's dispersal are facilitated by
      ongoing fisheries management practices. Therefore, immediate changes in fisheries
      management (i.e. stocking and translocation measures) and a detailed conservation
      plan, focussed on remnant purebred B. plebejus populations, are urgently needed.

PMID- 24103006
TI  - Complexities and opportunities in monitoring and evaluating US and global changes
      by the food industry.
AB  - In developed nations and increasingly in the rest of the world, a large
      proportion of people's diets comes from manufactured food sources and food not
      produced at home. These types of products are constantly changing and have
      significant nutrition and health implications for the world's population.
      However, researchers, public health workers and policy makers face major
      complexities in understanding what these changes are and their relationships to
      diet and health outcomes. This paper will describe some of the complexities faced
      in monitoring and evaluating the nutritional composition of food products and
      what it means for population health. Importantly, no existing food composition
      database is able to keep up with the continuous reformulation and introductions
      and removals of packaged foods and food services. The paper will also discuss
      opportunities to improve and update the monitoring and evaluation of changes made
      by each of these key sectors of the modern food supply and how these changes can
      influence the nutrients purchased or consumed across the globe. The focus will be
      on the United States with some examples from other developed nations and a
      discussion of implications for low- and middle-income countries. 

PMID- 24103007
TI  - An adult patient of double-chambered right ventricle with ventricular septal
      defect incidentally diagnosed after presentation with acute myocardial
      infarction.
AB  - The double-chambered right ventricle (DCRV) is a rare congenital heart disease
      caused by hypertrophic anomalous muscle bands that divide the ventricular cavity,
      resulting in the formation of a high-pressure proximal chamber and other low
      pressure distal one. Because of its evolving nature, its diagnosis is usually
      made during childhood/adolescence and very rarely during adulthood. It accounts
      for approximately 0.5-1% of patients with congenital heart disease. We report a
      case of a 50-year-old man who presented to us with acute inferior wall myocardial
      infarction (MI). Echocardiography revealed the features of DCRV and ventricular
      septal defect. Coronary angiogram revealed significant stenosis in right coronary
      artery. This is the first case where an adult patient with DCRV incidentally
      diagnosed after presentation with acute MI and had undergone successful coronary
      angioplasty. 

PMID- 24103008
TI  - Prognostic significance of extramural vascular invasion in T4 rectal cancer.
AB  - AIM: Extramural vascular invasion (EMVI) has been proposed as an adverse
      prognostic indicator in colorectal cancer, although its use remains both variable
      and controversial. This study aimed to determine the survival effect of EMVI in
      T4 rectal cancer. METHOD: Patients undergoing surgery with curative intent for
      primary T4 rectal cancer between 1971 and 2011 were included from two
      prospectively collected rectal cancer databases. The main end-point was 3-year
      survival. RESULTS: From 1142 patients undergoing resection of rectal cancer
      during the study period, 126 (11.0%) had T4 rectal cancer and were included in
      the study group. Sphincter preservation was performed in 61 (48%) and a
      pathologically negative resection margin (R0) was achieved in 104 patients
      (82.5%). EMVI was present in 51 patients (40.5%) and was an independent predictor
      of positive lymph node status (adjusted odds ratio 2.66, P = 0.013). Considering
      all patients, EMVI was associated with reduced overall survival (P = 0.007) and
      disease-free survival (P = 0.002), but not local recurrence-free survival (P =
      0.198). In only those undergoing R0 resection, EMVI predicted reduced disease
      free survival with positive nodal status (P = 0.021); it did not predict survival
      with negative nodal status. CONCLUSION: Overall, EMVI was a strong prognostic
      marker of survival. However, after complete surgical resection in patients with
      node-negative disease, EMVI did not predict local recurrence.

PMID- 24103009
TI  - Urinary type IV collagen as a predictor for the incidence of microalbuminuria in
      young patients with Type 1 diabetes.
AB  - AIMS: To clarify whether urinary type IV collagen-to-creatinine ratio is a
      predictor for the incidence of microalbuminuria in patients with Type 1 diabetes.
      METHODS: A longitudinal observational cohort study was conducted; the subjects
      included normoalbuminuric patients diagnosed with Type 1 diabetes before the age
      of 30 years and who were less than 40 years old at the start of the observation.
      In total, 225 patients were enrolled (age, mean +/- SD: 25 +/- 5 years; male:
      32.9%). The endpoint was the incidence of microalbuminuria, defined as 30 mg/g Cr
      <= urinary albumin-to-creatinine ratio < 300 mg/g Cr. Patients were divided into
      two groups based on the median of urinary type IV collagen-to-creatinine ratio
      levels. RESULTS: During the median follow-up period of 8.8 years (range 1.0-12.8
      years), 13 patients with high urinary type IV collagen-to-creatinine ratio
      progressed to microalbuminuria. Meanwhile, only one patient with low urinary type
      IV collagen-to-creatinine ratio reached the endpoint. Kaplan-Meier estimates for
      the time to reach the endpoint were significantly faster for patients with a high
      ratio than for those with a low ratio (log-rank test, P < 0.001). In the
      multivariate Cox hazard analysis, the hazard ratio for patients with high vs. low
      urinary type IV collagen-to-creatinine ratio was 13.51 (95% CI 1.59-115.02, P =
      0.017). When urinary type IV collagen-to-creatinine ratio was treated as a
      continuous variable, logarithmically transformed urinary type IV collagen-to
      creatinine ratio, but not baseline albumin-to-creatinine ratio, was independently
      associated with reaching the endpoint (hazard ratio 19.23, 95% CI 1.53-242.30, P
      = 0.022). CONCLUSIONS: Urinary type IV collagen may be an important predictor for
      the incidence of microalbuminuria in young patients with Type 1 diabetes.

PMID- 24103010
TI  - "Typical" cavotricuspid isthmus-dependent atrial flutter without the cava.

PMID- 24103011
TI  - Outcomes after pulmonary metastasectomy for colorectal cancer.
AB  - BACKGROUND: Surgical resection offers the greatest likelihood of cure for
      appropriately selected patients with pulmonary colorectal carcinoma metastases.
      We hereby report our experience over the last 19 years at the Austin Hospital,
      Thoracic Surgery Unit. METHODS: This is a retrospective study of a consecutive
      series of patients with pulmonary colorectal cancer metastases. From 1994 to
      2012, 66 patients underwent 83 pulmonary metastasectomies for colorectal cancer
      at the Austin Hospital. RESULTS: Seventy per cent of patients were operated on
      for single pulmonary metastases. The most common procedure performed was a video
      assisted thoracoscopic surgery wedge resection. Median follow-up duration was 25
      months. Three-, five-, seven- and ten-year survival was 53.4, 39.6, 34.6 and
      23.1%, respectively. CONCLUSION: Pulmonary metastasectomy for metastatic
      colorectal carcinoma continues to offer the greatest survival advantage for
      appropriately selected patients.

PMID- 24103012
TI  - SMG1 is an ancient nonsense-mediated mRNA decay effector.
AB  - Nonsense-mediated mRNA decay (NMD) is a eukaryotic process that targets selected
      mRNAs for destruction, for both quality control and gene regulatory purposes.
      SMG1, the core kinase of the NMD machinery in animals, phosphorylates the highly
      conserved UPF1 effector protein to activate NMD. However, SMG1 is missing from
      the genomes of fungi and the model flowering plant Arabidopsis thaliana, leading
      to the conclusion that SMG1 is animal-specific and questioning the mechanistic
      conservation of the pathway. Here we show that SMG1 is not animal-specific, by
      identifying SMG1 in a range of eukaryotes, including all examined green plants
      with the exception of A. thaliana. Knockout of SMG1 by homologous recombination
      in the basal land plant Physcomitrella patens reveals that SMG1 has a conserved
      role in the NMD pathway across kingdoms. SMG1 has been lost at various points
      during the evolution of eukaryotes from multiple lineages, including an early
      loss in the fungal lineage and a very recent observable gene loss in A. thaliana.
      These findings suggest that the SMG1 kinase functioned in the NMD pathway of the
      last common eukaryotic ancestor.

PMID- 24103013
TI  - Low oxygen tension and relative defined culture medium with 3, 4-dihydroxyflavone
      are beneficial for yak-bovine interspecies somatic cell nuclear transfer embryo.
AB  - With an aim to improve the efficiency of yak-bovine interspecies somatic cell
      nuclear transfer (iSCNT), this study investigated the effect of different culture
      systems on the development, quality and gene expression profile of yak-bovine
      iSCNT embryo. Reconstructed embryos were cultured in modified synthetic oviductal
      fluid (mSOF) or relative defined culture medium (RDCM) with 5% or 20% oxygen
      tension. Relative mRNA abundance of Oct-4, IFNT, IGF-2, Bax, GPX-1, SOD-1, CAT
      and GSS was analysed in blastocysts with qRT-PCR. The blastocyst formation rate
      in RDCM under 5% oxygen tension was significantly higher than that under 20%
      oxygen tension (P < 0.05). The total cell number of blastocyst derived from RDCM
      with 20% oxygen tension was lower than that of other groups, whereas the group of
      RDCM with 5% oxygen tension showed a beneficial effect on apoptosis index and
      tolerance to cryopreservation (P < 0.05). However, under the same oxygen tension,
      the mRNA abundance of IFNT of RDCM groups was higher than that of the mSOF
      groups. In addition, high oxygen tension during in vitro culture (IVC) with RDCM
      significantly increases the mRNA expression of oxidative stress-related genes
      (GPX-1, SOD-1, CAT and GSS) (P < 0.05). 3, 4-Dihydroxyflavone (DHF) during high
      oxygen tension was able to improve the cloned blastocyst formation rate in RDCM
      (P < 0.05). These results for the first time showed that low oxygen tension and
      RDCM could improve the developmental competence and quality and alleviate the
      oxidative stress for yak-bovine iSCNT embryo during IVC. 

PMID- 24103014
TI  - Evaluation of ultrasound-guided vascular access in dogs.
AB  - OBJECTIVE: To describe the technique and determine the feasibility, success rate,
      perceived difficulty, and time to vascular access using ultrasound guidance for
      jugular vein catheterization in a cardiac arrest dog model. DESIGN: Prospective
      descriptive study. SETTING: University teaching hospital. ANIMALS: Nine Walker
      hounds. MEASUREMENTS AND MAIN RESULTS: A total of 27 jugular catheterizations
      were performed postcardiac arrest using ultrasound guidance. Catheterizations
      were recorded based on the order in which they were performed and
      presence/absence of a hematoma around the vein. Time (minutes) until successful
      vascular access and perceived difficulty in achieving vascular access (scale of 1
      = easy to 10 = difficult) were recorded for each catheterization. Mean time to
      vascular access was 1.9 minutes (95% confidence interval, 1.1-3.4 min) for
      catheterizations without hematoma, versus 4.3 minutes (1.8-10.1 min) for
      catheterizations with hematoma (P = 0.1). Median perceived difficulty was 2 of 10
      (range 1-7) for catheterizations without hematoma, versus 2 of 10 (range 1-8) for
      catheterizations with hematoma (P = 0.3). A learning curve was evaluated by
      comparing mean time to vascular access and perceived difficulty in initial versus
      subsequent catheterizations. Mean time to vascular access was 2.5 minutes (1.0
      6.4 min) in the initial 13 catheterizations versus 3.3 minutes (1.5-7.5 min) in
      the subsequent 14 catheterizations (P = 0.6). Median perceived difficulty in the
      first 13 catheterizations (3, range 1-8) was significantly greater (P = 0.049)
      than median perceived difficulty in the subsequent 14 catheterizations (2, range
      1-6). CONCLUSIONS: Ultrasound-guided jugular catheterization is associated with a
      learning curve but is successful in obtaining rapid vascular access in dogs.
      Further prospective studies are warranted to confirm the utility of this
      technique in a clinical setting.

PMID- 24103015
TI  - Elastographic characteristics of the metacarpal tendons in horses without
      clinical evidence of tendon injury.
AB  - Tendon and ligament injuries are common causes of impaired performance in equine
      athletes. Gray-scale ultrasonography is the current standard method for
      diagnosing and monitoring these injuries, however this modality only provides
      morphologic information. Elastography is an ultrasound technique that allows
      detection and measurement of tissue strain, and may provide valuable mechanical
      information about equine tendon and ligament injuries. The purpose of this study
      was to determine the feasibility, reproducibility, and repeatability of
      elastography; and to describe elastographic characteristics of metacarpal tendons
      in sound horses. Nineteen legs for 17 clinically sound horses without evidence of
      musculoskeletal pathology were included. Elastographic images of the superficial
      and deep digital flexor tendons and the branches of the suspensory ligament
      (tendon of the interosseous muscle) were described quantitatively and
      qualitatively. There was no statistically significant difference between
      operators (P = 0.86) nor within operators (P = 0.93). For qualitative
      assessments, reproducibility (0.46) was moderate and repeatability (0.78) was
      good. Similar to human Achilles tendons, equine tendons were classified as
      predominantly hard using elastography. There was no statistically significant
      difference in stiffness of the flexor tendons (P = 0.96). No significant
      difference in stiffness was found with altered leg position during standing (P =
      0.84) and while nonweight bearing (P = 0.61). The flexor tendons were softer when
      imaged in longitudinal versus transverse planes (P < 0.01) however, the
      suspensory branches were not (P = 0.67). Findings supported future clinical
      application of elastography as a noninvasive "stall-side" imaging modality for
      evaluation of the tendons and ligaments of the distal forelimb in horses. 

PMID- 24103017
TI  - Optical coherence tomography imaging of non-melanoma skin cancer undergoing
      imiquimod therapy.
AB  - PURPOSE: To explore the application of optical coherence tomography (OCT) imaging
      of basal cell carcinomas (BCC) and actinic keratosis (AK) before, during and
      after imiquimod treatment and the ability of OCT to predict treatment outcome.
      METHODS: The study subjects were 20 patients with biopsy-verified BCC (9) or AK
      (11). Patients were OCT-scanned before, after 1 and 4 weeks of imiquimod
      treatment and after 3 months. Lesions were identified clinically and with OCT.
      Thickness and morphology of the lesions were recorded at each visit. Any
      remaining lesions were biopsied at follow-up. RESULTS: Complete data sets were
      available for 16 patients (8 women and 8 men aged 52-82 years), four in-compliant
      patients were excluded. OCT identified all lesions. Previously suggested OCT
      criteria identified 5/8 BCCs. Crusting, ulceration and active treatment
      significantly reduced image quality. All BCCs cleared, but at follow-up residual
      structures were seen clinically in 4 cases. OCT and histology both ruled out
      residual BCC. For AKs significant thinning occurred after 1 week of treatment (P
      = 0.04). Imiquimod cleared 2/8 AKs, and significantly decreased the thickness of
      all lesions (P = 0.02). CONCLUSIONS: OCT could identify superficial BCC and AK
      before treatment. Monitoring during imiquimod treatment revealed impaired image
      quality most likely caused by inflammation, crusting and ulceration. On follow
      up, OCT showed thinning of AKs indicating effect of treatment. All treated BCCs
      cleared, but where residual tissue was suspected clinically this could be ruled
      out by OCT.

PMID- 24103016
TI  - Functional integrity of the habenula is necessary for social play behaviour in
      rats.
AB  - During post-weaning development, a marked increase in peer-peer interactions is
      observed in mammals, including humans, which is signified by the abundance of
      social play behaviour. Social play is highly rewarding, and known to be modulated
      through monoaminergic neurotransmission. Recently, the habenula has received
      widespread attention because of its role in the regulation of monoaminergic
      neurotransmission as well as in a variety of emotional and cognitive functions.
      Therefore, in the present study, we investigated the involvement of the habenula
      in social play behaviour. Using the neuronal activity maker c-fos, we showed that
      the habenula was activated after 24 h of social isolation in adolescent rats, and
      that a subsequent social play interaction reduced c-fos activity in the medial
      part of the lateral habenula. This suggested that habenula activity modulated the
      aversive properties of social isolation, which was alleviated by the positive
      effects of social play. Furthermore, after functional inactivation of the
      habenula, using a mixture of the GABA receptor agonists baclofen and muscimol,
      social play behaviour was markedly reduced, whereby responsiveness to play
      solicitation was more sensitive to habenula inactivation than play solicitation
      itself. Together, our data indicate an important role for the habenula in the
      processing of positive (i.e., social play behaviour) and negative (i.e., social
      isolation) social information in adolescent rats. Altered habenula function might
      therefore be related to the social impairments in childhood and adolescent
      psychiatric disorders such as autism, attention deficit/hyperactivity disorder
      and early-onset schizophrenia.

PMID- 24103018
TI  - Neurotoxicity of sedative and analgesia drugs in young infants with congenital
      heart disease: 4-year follow-up.
AB  - OBJECTIVES/AIM: To determine whether sedation/analgesia drugs used before,
      during, and after infant cardiac surgery are associated with neurocognitive and
      functional outcomes. BACKGROUND: Some animal models suggest neurotoxic effects of
      anesthetic drugs on the developing brain; however, potential human effects are
      unknown. Whether these results can be extrapolated to humans is unknown.
      METHODS/MATERIALS: Prospective follow-up project of all infants <=6 weeks old
      having surgery for congenital heart disease between 04/03 and 12/06. Demographic,
      perioperative, and sedation/analgesia variables were collected. Outcomes at
      kindergarten age were Wechsler Preschool and Primary Scale of Intelligence-III,
      Beery-Buktenica Developmental Test of Visual Motor Integration (VMI-V), and
      General Adaptive Composite (GAC) of the Adaptive Behavior Assessment System-II.
      Multivariable linear regression was used to identify predictor variables.
      RESULTS: From 135 infants who underwent heart surgery, 19 died, 17 were excluded,
      8 were lost to follow-up, leaving 91 children for analysis. Multiple linear
      regression found days on chloral hydrate [3.5 (3.7) days] was associated with
      lower performance intelligence quotient (PIQ) (Effect size -1.03; 95% CI -1.96, 
      0.10; P = 0.03), and cumulative dose [54.2 (60.3) mg.kg(-1) ] of benzodiazepines
      was associated with lower VMI scores (Effect size -0.07; 95% CI -0.12, -0.01; P =
      0.026). No other associations were found between sedation/analgesia variables and
      full-scale IQ, PIQ, Verbal IQ, VMI, or GAC. CONCLUSION: Assessment of this cohort
      at kindergarten age found a small statistically significant association between
      days on chloral hydrate and PIQ, and benzodiazepine cumulative dose and lower
      VMI. No other association between sedation/analgesia drugs and outcomes was
      found.

PMID- 24103020
TI  - Immunohistochemical characterization of prototypical endometrial clear cell
      carcinoma--diagnostic utility of HNF-1beta and oestrogen receptor.
AB  - AIMS: The great majority of ovarian clear cell carcinomas have a hepatocyte
      nuclear factor 1 homeobox B (HNF-1beta)-positive and oestrogen receptor (ER)
      negative immunoprofile. However, the pattern of HNF-1beta and ER immunostaining
      in clear cell carcinomas of the endometrium and the usefulness of this panel in
      distinguishing clear cell carcinoma from other histological types of endometrial
      carcinoma have yet to be well defined. METHODS AND RESULTS: We examined the
      immunostaining patterns of HNF-1beta, ER and p53 in 15 morphologically classic
      pure endometrial clear cell carcinomas, and compared these patterns with 15
      endometrioid and 15 serous carcinomas of the endometrium. We observed the
      presence of diffuse (>70%) moderate to strong nuclear HNF-1beta staining and
      negative ER staining in 14 of 15 clear cell carcinomas, with the remaining case
      showing both diffuse strong nuclear HNF-1beta staining and focal ER staining. In
      comparison, only one of 15 serous carcinomas and none of 15 endometrioid
      carcinomas showed a combination of diffuse moderate to strong HNF-1beta nuclear
      staining and negative ER staining. Aberrant p53 immunostaining was observed in
      five of 15 (33%) clear cell carcinomas. CONCLUSIONS: Overall, our findings
      demonstrate that, similarly to the situation for the ovary, a diagnostic panel of
      HNF-1beta and ER may be considered for separating clear cell carcinoma from
      endometrioid and serous carcinoma of the endometrium.

PMID- 24103019
TI  - Evaluation of the performance of the microscopic observation drug susceptibility
      assay for diagnosis of extrapulmonary tuberculosis in China: A preliminary study.
AB  - BACKGROUND AND OBJECTIVE: While commercial liquid culture techniques have emerged
      over 20 years ago, Ziehl-Neelsen (ZN) smear microscopy remains the primary method
      for diagnosis of tuberculosis (TB) in China because of cost considerations. The
      microscopic observation drug susceptibility (MODS) assay has been evaluated in
      different parts of the world to determine whether it can give comparable result
      to commercial liquid techniques. However, most reports detail evaluation of
      sputum specimens. This study evaluated the performance of MODS assay for
      detection of Mycobacterium tuberculosis in extrapulmonary specimens in a Chinese
      population. METHODS: A total of 173 samples, including pleural fluid (n = 112)
      and cerebrospinal fluid (CSF, n = 61) samples, were collected from patients
      suspected to have extrapulmonary TB and tested by ZN smear microscopy, Lowenstein
      Jensen (LJ) culture and the MODS assay. Discordant results among MODS assay and
      the other two methods were resolved by 90-day follow-up evaluation for all
      suspected patients. RESULTS: The sensitivity of the MODS assay on pleural fluid
      and CSF samples was 20.5% and 37.5%, respectively, while the specificity of MODS
      assay on both types of samples approximated 100%. The median time to culture
      results for the MODS and LJ methods was 14 days, 32 days for pleural fluid, and 9
      days and 31 days for CSF samples, respectively. CONCLUSIONS: MODS assay is useful
      to diagnose extrapulmonary TB and may be an effective and affordable method in
      resource-limited countries.

PMID- 24103021
TI  - They're not your daddy's inherited platelet disorders anymore.

PMID- 24103022
TI  - Acquired hypogammaglobulinemia in HIV-positive subjects after liver
      transplantation.
AB  - INTRODUCTION: As more solid organ transplantations are performed in patients
      infected with human immunodeficiency virus (HIV), post-transplant complications
      in this population are becoming better defined. METHODS: Using serum samples from
      the Solid Organ Transplantation in HIV: Multi-Site Study, we studied the
      epidemiology of acquired hypogammaglobulinemia (HGG) after liver transplantation
      (LT) in 79 HIV-infected individuals with a median CD4 count at enrollment of 288
      (interquartile range 200-423) cells/MUL. Quantitative immunoglobulin G (IgG)
      levels before and after LT were measured, with moderate and severe HGG defined as
      IgG 350-500 mg/dL and <350 mg/dL, respectively. Incidence, risk factors, and
      associated outcomes of moderate or worse HGG were evaluated using Kaplan-Meier
      estimator and proportional hazards (PH) models. RESULTS: The 1-year cumulative
      incidence of moderate or worse HGG was 12% (95% confidence interval [CI]: 6-22%);
      no new cases were observed between years 1 and 2. In a multivariate PH model,
      higher pre-transplant model for end-stage liver disease score (P = 0.04) and
      treated acute rejection (P = 0.04) were both identified as significant predictors
      of moderate or worse HGG. There was a strong association of IgG levels <500 mg/dL
      with non-opportunistic serious infection (hazard ratio [95% CI]: 3.5 [1.1-10.6];
      P = 0.03) and mortality (3.2 [1.1-9.4]; P = 0.04). These associations held after
      adjustment for important determinants of infection and survival among the entire
      cohort. CONCLUSION: These results suggest that a proportion of HIV-positive LT
      recipients will develop clinically significant HGG after transplantation.

PMID- 24103023
TI  - Key role of salsolinol in ethanol actions on dopamine neuronal activity of the
      posterior ventral tegmental area.
AB  - Ethanol excites dopamine (DA) neurons in the posterior ventral tegmental area
      (pVTA). This effect is responsible for ethanol's motivational properties and may
      contribute to alcoholism. Evidence indicates that catalase-mediated conversion of
      ethanol into acetaldehyde in pVTA plays a critical role in this effect.
      Acetaldehyde, in the presence of DA, condensates with it to generate salsolinol.
      Salsolinol, when administered in pVTA, excites pVTA DA cells, elicits DA
      transmission in nucleus accumbens and sustains its self-administration in pVTA.
      Here we show, by using ex vivo electrophysiology, that ethanol and acetaldehyde,
      but not salsolinol, failed to stimulate pVTA DA cell activity in mice
      administered alpha-methyl-p-tyrosine, a DA biosynthesis inhibitor that reduces
      somatodendritic DA release. This effect was specific for ethanol and acetaldehyde
      since morphine, similarly to salsolinol, was able to excite pVTA DA cells in
      alpha-methyl-p-tyrosine-treated mice. However, when DA was bath applied in slices
      from alpha-methyl-p-tyrosine-treated mice, ethanol-induced excitation of pVTA DA
      neurons was restored. This effect requires ethanol oxidation into acetaldehyde
      given that, when H2 O2 -catalase system was impaired by either 3-amino-1,2,4
      triazole or in vivo administration of alpha-lipoic acid, ethanol did not enhance
      DA cell activity. Finally, high performance liquid chromatography-tandem mass
      spectrometry analysis of bath medium detected salsolinol only after co
      application of ethanol and DA in alpha-methyl-p-tyrosine-treated mice. These
      results demonstrate the relationship between ethanol and salsolinol effects on
      pVTA DA neurons, help to untangle the mechanism(s) of action of ethanol in this
      area and contribute to an exciting research avenue prosperous of theoretical and
      practical consequences. 

PMID- 24103024
TI  - A novel HLA-DRB1 allele, HLA-DRB1*13:116, identified by sequencing-based typing
      in a member of the Czech National Marrow Donor Registry.
AB  - We describe the identification of a novel HLA-DRB1 allele, DRB1*13:116, in a
      member of the Czech National Marrow Donor Registry. The novel allele differs from
      the known DRB1*13:17 variant by a nucleotide exchange at position 227 (T/A) of
      the coding HLA-DRB1 sequence, which causes an amino acid substitution (Phe47Tyr)
      in the HLA-DR beta 1 chain. 

PMID- 24103025
TI  - Australian medical students and their choice of surgery as a career: a review.
AB  - BACKGROUND: Surgery is an emotionally, physically and mentally challenging
      profession, and medical students factor in many variables when choosing surgery
      as a career choice. The aim of this study is to review the available literature
      on the factors influencing Australian medical students' choice of surgery as
      their career. METHOD: A search of EMBASE and MEDLINE with the search terms
      'medical students' AND 'surgery'; 'medical students' AND 'career pathways';
      'medical students' AND 'career choices' was conducted. Additionally, Google
      Scholar and the reference list of some articles were canvassed for suitable areas
      of study. RESULTS: Lifestyle factors were the main reason influencing medical
      student's career choices. A balance between work, family and lifestyle was found
      to be important, and a surgical career choice was not always compatible with
      this. In particular, female students placed more importance on family and
      lifestyle factors when opting for non-surgical careers. Positive exposure and/or
      experiences in a surgical environment, perceived prestige and perceived financial
      reward were associated with surgical career choice. CONCLUSIONS: There is a need
      to better understand the factors influencing surgical and non-surgical career
      choice among Australian medical students, and develop appropriate interventions
      to promote surgery as a career. This article does not discuss personality traits
      of people who go into surgery.

PMID- 24103026
TI  - Mexico attempts to tackle obesity: the process, results, push backs and future
      challenges.
AB  - Mexico's obesity prevalence is one of the world's highest. In 2006, academics,
      and federal and state government agencies initiated efforts to design a national
      policy for obesity prevention. The Ministry of Health (MOH) established an expert
      panel to develop recommendations on beverage intake for a healthy life in 2008.
      Subsequently, the MOH, with support from academia, initiated the development of
      the National Agreement for Healthy Nutrition (ANSA). ANSA was signed by all
      relevant sectoral actors in 2010 and led to initiatives banning sodas and
      regulating unhealthy food in schools and the design of other yet to be
      implemented initiatives, such as a front-of-package labeling system. A main
      challenge of the ANSA has been the lack of harmonization between industry
      interests and public health objectives and effective accountability and
      monitoring mechanisms to assess implementation across government sectors. Bold
      strategies currently under consideration include taxation of sugar-sweetened
      beverages, improvement of norms for healthy food in schools, regulation of food
      and beverage marketing to children and implementation of a national front-of-pack
      labeling system. Strong civil society organizations have embraced the prevention
      of obesity as their goal and have used evidence from academia to position obesity
      prevention in the public debate and in the government agenda. 

PMID- 24103027
TI  - Thyroid autoimmunity in Type 1 diabetes: systematic review and meta-analysis.
AB  - AIMS: To review the incidence and evidence for screening for thyroid autoimmunity
      and thyroid dysfunction in Type 1 diabetes. METHODS: Systematic review and meta
      analysis. Inclusion criteria were prospective cohort studies screening for
      thyroid autoimmunity and/or dysfunction (defined as an abnormal thyroid
      stimulating hormone level) in Type 1 diabetes. Exclusion criteria included
      pregnancy and thyroid dysfunction before diabetes onset. Outcomes examined were:
      incidence of thyroid autoimmunity and/or dysfunction; association between thyroid
      autoimmunity and dysfunction; and cost-effectiveness. Data sources were MEDLINE,
      EMBASE, the Cochrane Library, manual searching and contact with authors, with
      limitations to English language and human studies. Meta-analysis was performed
      using random effects models. RESULTS: We identified 14 eligible studies,
      involving 2972 young people and 789 adults with Type 1 diabetes. Follow-up ranged
      from 1-18 years. None of the studies were of good methodological quality
      (Newcastle Ottowa Scale score > 7). The incidence of thyroid dysfunction (11
      studies) ranged from 27 (95% CI 15-45) to 246 (95% CI 118-453) per 10 000 patient
      years and thyroid autoimmunity (four studies) from 13 (95% CI 0.3-71) to 326 (95%
      CI 194-510). The risk of thyroid dysfunction was higher in those with thyroid
      autoimmunity: summary risk ratio 25 (95% CI 9-71) and was higher in children (49,
      95% CI 16-150) compared with adults (7, 95% CI 3-13). No studies examined cost
      effectiveness of screening. CONCLUSIONS: There is a markedly increased risk of
      thyroid dysfunction in people with Type 1 diabetes and thyroid autoimmunity. The
      optimal method or frequency of screening could not be determined from available
      data. Future studies should examine whether screening improves clinical outcomes
      in this population.

PMID- 24103028
TI  - Saccade and vergence eye movements: a review of motor and premotor commands.
AB  - Neuropsychology examines the relationship between cognitive activity and
      corresponding cerebral conditions. At one end, psychophysics meticulously
      describes the details of behavior. At the other, physiology records brain cell
      activity during cognitive tasks. Bridging the two, neuropsychology establishes
      the neural correlate of behaviour when correlation methods are used, and extends
      to the critical neural substrate when a causal relationship can be established.
      Here we revisit the Hering-versus-Helmholtz controversy on binocular coordination
      from the psychophysician's description of combined saccade-vergence eye movements
      to the neurophysiological recording of motor and premotor neurons of the
      oculomotor neural circuitry. Whilst neo-Heringian psychophysicians and
      physiologists have accumulated arguments for separate saccade and vergence
      systems, at both the behavioral and the neural premotor levels, neo-Helmholtzians
      have also provided evidence for monocular programmed eye movements and commands
      at the premotor level. Bridging the two, we conclude that Hering and Helmholtz
      were both right. Importantly, the latter's viewpoint brings to the fore the
      importance of adaptive processes throughout life, in view of the neurobiological
      constraints emphasized by the former. 

PMID- 24103029
TI  - Necroptosis in immunity and ischemia-reperfusion injury.
AB  - Transplantation is invariably associated with ischemia-reperfusion injury (IRI),
      inflammation and rejection. Resultant cell death has morphological features of
      necrosis but programmed cell death has been synonymous with apoptosis until
      pathways of regulated necrosis (RN) have been described. The best-studied RN
      pathway, necroptosis, is triggered by perturbation of caspase-8-mediated
      apoptosis and depends on receptor-interacting protein kinases 1 and 3
      (RIPK1/RIPK3) as well as mixed linage kinase domain like to form the
      necroptosome. The release of cytosolic content and cell death-associated
      molecular patterns (CDAMPs) can trigger innate and promote adaptive immune
      responses. Thus, the form of cell death can substantially influence alloimmunity
      and graft survival. Necroptosis is a key element of IRI, and RIPK1 interference
      by RN-specific inhibitors such as necrostatin-1 protects from IRI in kidney,
      heart and brain. Necroptosis may be a general mechanism in response to other
      forms of inflammatory organ injury, and will likely emerge as a promising target
      in solid organ transplantation. As second-generation RIPK1 and RIPK3 inhibitors
      become available, clinical trials for the prevention of delayed graft function
      and attenuation of allograft rejection-mediated injury will emerge. These efforts
      will accelerate upon further identification of critical necroptosis-triggering
      receptor(s). 

PMID- 24103030
TI  - Population structure of the Chagas disease vector, Triatoma infestans, at the
      urban-rural interface.
AB  - The increasing rate of biological invasions resulting from human transport or
      human-mediated changes to the environment has had devastating ecological and
      public health consequences. The kissing bug, Triatoma infestans, has dispersed
      through the Peruvian city of Arequipa. The biological invasion of this insect has
      resulted in a public health crisis, putting thousands of residents of this city
      at risk of infection by Trypanosoma cruzi and subsequent development of Chagas
      disease. Here, we show that populations of Tria. infestans in geographically
      distinct districts within and around this urban centre share a common recent
      evolutionary history although current gene flow is restricted even between
      proximal sites. The population structure among the Tria. infestans in different
      districts is not correlated with the geographical distance between districts.
      These data suggest that migration among the districts is mediated by factors
      beyond the short-range migratory capabilities of Tria. infestans and that human
      movement has played a significant role in the structuring of the Tria. infestans
      population in the region. Rapid urbanization across southern South America will
      continue to create suitable environments for Tria. infestans, and knowledge of
      its urban dispersal patterns may play a fundamental role in mitigating human
      disease risk.

PMID- 24103031
TI  - Downregulation of postsynaptic density-95-interacting regulator of spine
      morphogenesis reduces glutamate-induced excitotoxicity by differentially
      regulating glutamate receptors in rat cortical neurons.
AB  - Glutamate-induced excitotoxicity is involved in many neurological diseases.
      Preso, a novel postsynaptic scaffold protein, mediates excitatory synaptic
      transmission and various synaptic functions. In this study, we investigated the
      role of Preso in the regulation of glutamate-induced excitotoxicity in rat
      cortical neurons. Knockdown of Preso with small interfering RNA improved neuronal
      viability and attenuated the elevation of lactate dehydrogenase (LDH) release
      after glutamate treatment. Downregulation of Preso also inhibited an increase in
      the BAX/Bcl-2 ratio and cleavage of caspase-9 and caspase-3. Although the
      expression and distribution of metabotropic glutamate receptor (mGluR) 1/5, NR1,
      NR2A and NR2B were not changed by knockdown of Preso, downregulation of Preso
      protected neurons from glutamate-induced excitotoxicity by inhibiting mGluR and N
      methyl-D-aspartate receptor function. However, downregulation of Preso neither
      affected the expression of GluR1 and GluR2 nor influenced the function of alpha
      amino-3-hydroxy-5-methyl-4-isoxazole propionate receptor after glutamate
      treatment. Furthermore, intracellular Ca(2+) was an important downstream effector
      of Preso in the regulation of excitotoxicity. These results suggest that
      expression of Preso promotes the induction of excitotoxicity by facilitating
      different glutamate receptor signaling pathways. Therefore, Preso might be a
      potential pharmacological target for preventing and treating neurological
      diseases.

PMID- 24103032
TI  - Wide complex tachycardia: what is the mechanism?

PMID- 24103033
TI  - Workplace social capital in nursing: an evolutionary concept analysis.
AB  - AIM: To report an analysis of the concept of nurses' workplace social capital.
      BACKGROUND: Workplace social capital is an emerging concept in nursing with
      potential to illuminate the value of social relationships at work. A common
      definition is needed. DESIGN: Concept analysis. DATA SOURCES: The Cumulative
      Index to Nursing and Allied Health Literature, PubMed, PsychINFO and ProQuest
      Nursing. REVIEW METHODS: Databases were systematically searched using the
      keywords: workplace social capital, employee social capital, work environment,
      social capital and nursing. Sources published between January 1937-November 2012
      in English that described or studied social capital of nurses at work were
      included. A total of 668 resources were found. After removing 241 duplicates,
      literature was screened in two phases: (1) titles and abstracts were reviewed (n
      = 427); and (2) remaining data sources were retrieved and read (n = 70). Eight
      sources were included in the final analysis. RESULTS: Attributes of nurses'
      workplace social capital included networks of social relationships at work,
      shared assets and shared ways of knowing and being. Antecedents were
      communication, trust and positive leadership practices. Nurses' workplace social
      capital was associated with positive consequences for nurses, their patients and
      healthcare organizations. CONCLUSION: Nurses' workplace social capital is defined
      as nurses' shared assets and ways of being and knowing that are evident in, and
      available through, nurses' networks of social relationships at work. Future
      studies should examine and test relationships between antecedents and
      consequences of nurses' workplace social capital to understand this important
      aspect of healthy professional practice environments better.

PMID- 24103034
TI  - Two-week wait symptoms are prevalent in screened patients with a positive faecal
      occult blood test but do not predict cancer.
AB  - AIM: Lower gastrointestinal (LGI) symptoms are prevalent in patients screened for
      bowel cancer yet do not predict a finding of cancer. This study evaluates
      symptoms in patients with these characteristics against the 2-week wait (2ww)
      criteria to determine whether they predicted cancer in these patients. METHOD: A
      prospective cohort study was performed. Patients with a positive faecal occult
      blood (FOB) test attending our unit over a 7-month period were included. Data on
      symptom prevalence, frequency and duration were collected and assessed against
      the 2ww criteria. Associations between symptom prevalence and patient outcome
      were investigated using the chi(2) test. RESULTS: Three hundred and ninety-seven
      patients were included and 37 (9%) were found to have colorectal cancer (CRC).
      The prevalence of undefined LGI symptoms was 71% and appeared comparable between
      those with and without CRC (65 vs 72%, P = 0.385). 2ww symptoms were reported in
      147 (37%), with 2ww change in bowel habit in 10% and 2ww rectal bleeding in 31%.
      2ww symptom prevalence was similar in those with and without cancer (38 vs 37%, P
      = 0.915). No significant differences in overall 2ww prevalence or prevalence of
      individual 2ww symptoms were demonstrated between those with a normal colonoscopy
      or one showing cancer, polyps or other pathology. Twenty nine per cent of
      patients with 2ww symptoms had reported these to their GP. CONCLUSION: Undefined
      LGI symptoms are prevalent in FOB-positive patients but do not predict CRC. 2ww
      symptoms are also highly prevalent, yet similarly fail to predict cancer. Further
      efforts to increase public awareness of cancer symptoms are required, whilst
      false reassurance from a negative FOB result should be discouraged.

PMID- 24103035
TI  - Virus-induced gene silencing identifies Catharanthus roseus 7-deoxyloganic acid-7
      hydroxylase, a step in iridoid and monoterpene indole alkaloid biosynthesis.
AB  - Iridoids are a major group of biologically active molecules that are present in
      thousands of plant species, and one versatile iridoid, secologanin, is a
      precursor for the assembly of thousands of monoterpenoid indole alkaloids (MIAs)
      as well as a number of quinoline alkaloids. This study uses bioinformatics to
      screen large databases of annotated transcripts from various MIA-producing plant
      species to select candidate genes that may be involved in iridoid biosynthesis.
      Virus-induced gene silencing of the selected genes combined with metabolite
      analyses of silenced plants was then used to identify the 7-deoxyloganic acid 7
      hydroxylase (CrDL7H) that is involved in the 3rd to last step in secologanin
      biosynthesis. Silencing of CrDL7H reduced secologanin levels by at least 70%, and
      increased the levels of 7-deoxyloganic acid to over 4 mg g(-1) fresh leaf weight
      compared to control plants in which this iridoid is not detected. Functional
      expression of this CrDL7H in yeast confirmed its biochemical activity, and
      substrate specificity studies showed its preference for 7-deoxyloganic acid over
      other closely related substrates. Together, these results suggest that
      hydroxylation precedes carboxy-O-methylation in the secologanin pathway in
      Catharanthus roseus.

PMID- 24103036
TI  - Structure-activity relationship of human bone sialoprotein peptides.
AB  - In the current study, the relationship between the structure of the RGD
      containing human bone sialoprotein (hBSP) peptide 278-293 and its attachment
      activity toward osteoblast-like (MC3T3) cells was investigated. This goal was
      accomplished by examining the comparative cell-attachment activities of several
      truncated forms of peptide 278-293. Computer modeling of the various peptides was
      also performed to assess the role of secondary structure in peptide bioactivity.
      Elimination of tyrosine-278 at the N-terminus resulted in a more dramatic loss of
      cell-attachment activity compared with the removal of either tyrosine-293 or the
      arg-ala-tyr (291-293) tripeptide. Although replacement of the RGD (arg-gly-asp)
      peptide moiety with peptide KAE (lys-ala-glu) resulted in a dramatic loss of cell
      attachment activity, a peptide containing RGE (arg-gly-glu) in place of RGD
      retained 70-85% of the parental peptide's attachment activity. These results
      suggest that the N-terminal RGD-flanking region of hBSP peptide 278-293, in
      particular the tyrosine-278 residue, represents a second cell-attachment site
      that stabilizes the RGD-integrin receptor complex. Computer modeling also
      suggested that a beta-turn encompassing RGD or RGE in some of the hBSP peptides
      may facilitate its binding to integrins by increasing the exposure of the
      tripeptide. This knowledge may be useful in the future design of biomimetic
      peptides which are more effective in promoting the attachment of osteogenic cells
      to implant surfaces in vivo. 

PMID- 24103037
TI  - Effectiveness of seasonal influenza vaccine in preventing medically attended
      influenza infection in England and Wales during the 2010/2011 season: a primary
      care-based cohort study.
AB  - BACKGROUND: Estimates of seasonal influenza vaccine effectiveness (VE) are
      affected by factors such as the strain of the current circulating influenza virus
      and characteristics of the host. OBJECTIVE: The objective of this study was to
      provide VE estimates for the 2010/2011 seasonal trivalent influenza vaccine (TIV)
      in preventing medically attended influenza in England and Wales for the season
      2010/2011. METHODS: A cohort study design was employed using electronic health
      records extracted from 104 GP practices in the Royal College of General
      Practitioners (RCGP) primary care sentinel network. Endpoints included influenza
      like illness (ILI), lower respiratory tract infection (LTRI) as well as PCR
      confirmed influenza from patients swabbed from practices participating in a
      swabbing scheme. Adjustment was made for age, month, underlying chronic
      condition, region and number of consultations in the 12 months prior to the study
      period. In addition to the cohort analysis, a nested test-negative case-control
      analysis (TNCC) was carried out using the swab-negative results as controls.
      RESULTS: In the cohort analysis, VE against LRTI was -0.5% [95% CI: (-7.0%,
      7.5%)], against ILI was 37.8% [95% CI: (32.3%, 43.0%)] and against PCR-confirmed
      influenza was 50.0% [95% CI:(25.9%, 65.6%)] for type A and 44.4% [95% CI: (10.1%,
      65.6%)] for type B. Using the TNCC design, the type A VE was 56.5% [95% CI:
      (30.4%, 72.7%)] and for type B was 54.0% [95% CI: (21.0%, 73.3%)]. CONCLUSIONS:
      This study shows that the 2010/2011 TIV provided moderate protection against the
      circulating influenza strains for the 2010/2011 season. It also suggests that VE
      against the less specific diagnosis of ILI can be found, but less specific
      endpoints such as LRTI are not useful.

PMID- 24103038
TI  - Right ventricular wall-motion changes after infant open heart surgery--a tissue
      Doppler study.
AB  - BACKGROUND: Right ventricular (RV) dysfunction is a well-recognized complication
      of cardiopulmonary bypass surgery (CPB) in adults. Infants and neonates may also
      be at high risk for this due to immature myocardium. Conventional assessment of
      RV function is just qualitative, but novel tissue Doppler echocardiographic (TDI)
      markers including peak systolic strain rate (SR) and isovolumic contraction
      acceleration (IVA) permit noninvasive quantitation of RV function. This study
      assessed myocardial velocities, IVA and SR in infants and neonates undergoing
      open heart surgery using TDI to study regional myocardial function
      perioperatively. METHODS: Transthoracic TDI data were obtained in the OR before
      and 24 hours post-CPB on 53 consecutive infants (age 0.39 +/- 0.23 years). They
      were followed with TDI through hospital discharge. RESULTS: Mean CPB time was 87
      +/- 49 min (cross-clamp 52 +/- 26 min). Peak systolic (STDI ) and diastolic
      myocardial velocities (ETDI , ATDI ), IVA, and peak SR were recorded in RV and LV
      from standard views for offline analysis. Postoperatively, LV systolic function
      and diastolic longitudinal function were unchanged or improved from baseline. LV
      radial velocities were increased postoperatively indicating adequate support. In
      contrast, RV longitudinal systolic and diastolic function was significantly
      diminished after CPB. RV changes persisted through hospital discharge.
      CONCLUSIONS: In infants and neonates, perioperative measurements of systolic and
      diastolic tissue Doppler parameters are feasible and revealed significant RV
      systolic and diastolic dysfunction post-CPB with preserved LV function. As such,
      TDI provides a sensitive tool to monitor the infant heart after CPB and may
      potentially be useful to assess different myocardial protection strategies.

PMID- 24103039
TI  - The SNAP index does not correlate with the State Behavioral Scale in intubated
      and sedated children.
AB  - BACKGROUND: Ensuring appropriate levels of sedation for critically ill children
      is integral to pediatric critical care. Traditionally, clinicians have used
      subjective scoring tools to assess sedation levels. The SNAP II uses dual
      frequency processed electroencephalography to evaluate brain activity and may
      provide an objective assessment of sedation levels. OBJECTIVE: This study
      attempts to find an objective method to monitor sedation in critically ill
      pediatric patients. We compared the SNAP II, a processed electroencephalography
      device, with the State Behavioral Scale (SBS), a subjective sedation scoring
      tool. We hypothesize that the SNAP II correlates with the SBS and has less
      observer bias. METHODS: This was an IRB approved prospective, observational
      study. Patients receiving intravenous sedation while being mechanically
      ventilated were enrolled after informed consent. After the SNAP II monitoring
      electrodes were attached, blinded bedside nurses assessed sedation levels using
      the SBS. SNAP indices were collected and compared with SBS scores to determine
      correlation. RESULTS: We compared 417 paired data points from 15 patients using
      Pearson's correlation and least squares means to determine correlation between
      the SBS and SNAP indices. No correlation was observed. Using covariance model
      patterning for repeated measures to adjust for covariates again showed no
      correlation. CONCLUSION: The SNAP index does not correlate with SBS scores in our
      pediatric intensive care unit (PICU). Its use cannot be recommended to measure
      levels of sedation in our population. Future research should continue to explore
      objective ways of measuring sedation in critically ill children.

PMID- 24103040
TI  - Pilot study of a brief intervention based on the theory of planned behaviour and
      self-identity to increase chlamydia testing among young people living in deprived
      areas.
AB  - OBJECTIVES: This study sought to estimate the effects of a novel intervention,
      compared with usual chlamydia testing promotion, on chlamydia test uptake and
      intentions among young people living in deprived areas. The intervention was
      based on the theory of planned behaviour, augmented with self-identity, and
      targeted the significant predictors of chlamydia testing intentions identified in
      the previous research. METHODS: Cluster randomization was used to allocate
      college tutor groups (intervention n = 10; control n = 11) to the intervention or
      control group. The sample comprised 253 participants (intervention n = 145,
      control n = 108). The primary outcome was test offer uptake at the end of the
      session. Other outcomes measured at immediate follow-up were intention, attitude,
      subjective norm, perceived behavioural control, and self-identity. RESULTS:
      Generalized estimating equations, controlling for cluster effects and sexual
      activity, found a small but non-significant effect of condition on test offer
      uptake, OR = 1.65 (95% CI 0.70, 3.88) p = .25, with 57.5% of intervention
      participants accepting the offer of a test compared with 40.2% of control
      participants. Using the same analysis procedure, small-to-medium intervention
      effects were found on other outcome variables, including a significant effect on
      attitudes towards chlamydia testing, OR = 1.37 (95% CI 1.00, 1.87), p = .05.
      CONCLUSIONS: The results provide encouraging initial evidence that this theory
      based intervention, targeting the key determinants of chlamydia testing, may help
      to improve chlamydia testing uptake in a high-risk group. They support the
      conduct of a larger trial to evaluate the effectiveness of the intervention.
      STATEMENT OF CONTRIBUTION: What is already known on this subject? Young people
      living in areas of increased socio-economic deprivation have been identified as a
      high-risk group for chlamydia. Previous research within an extended model of the
      theory of planned behaviour (TPB) found that attitude, subjective norm, perceived
      behavioural control, and self-identity all significantly predicted chlamydia
      testing intentions in this high-risk group. What does this study add? Development
      and testing of a novel, TPB-based intervention targeting predictors of chlamydia
      testing intentions. The intervention led to significantly more positive attitudes
      towards chlamydia testing. Preliminary indication that a TPB-based intervention
      may help to improve chlamydia testing in a high-risk group.

PMID- 24103041
TI  - Legalization of Sunday alcohol sales and alcohol consumption in the United
      States.
AB  - AIMS: To investigate the relationship between legalization of Sunday alcohol
      sales and alcohol consumption in the United States. DESIGN: State-level per
      capita consumption of beer, wine and spirits was analyzed using difference-in
      differences econometric methods. SETTING: United States. PARTICIPANTS: Five
      treatment states that repealed their laws restricting Sunday alcohol sales during
      1990-2007 and 12 control states that retained their Sunday alcohol laws during
      the same period. MEASUREMENTS: Outcome measures are state-level per capita
      consumption of overall alcohol, beer, wine and spirits. FINDINGS: Among the
      states that legalized Sunday sales of alcoholic beverages, Delaware, Pennsylvania
      and New Mexico experienced significant increases in overall alcohol consumption
      (P < 0.05). However, the effect of the legalization of Sunday alcohol sales in
      Massachusetts and Rhode Island on per capita alcohol consumption was
      insignificant (P = 0.964 and P = 0.367). CONCLUSIONS: Three out of five states in
      the United States that repealed their laws restricting Sunday sale of alcoholic
      beverages during 1990-2007 experienced significant increases in per capita
      alcohol consumption. This finding implies that increased alcohol availability
      leads to an increase in alcohol consumption.

PMID- 24103042
TI  - Clinical predictors of severe acute pancreatitis: value-adding the view from the
      end of the bed.
AB  - BACKGROUND: Research into clinical determinants of severe acute pancreatitis
      remains important for therapeutic and preventive purposes. To contribute to
      prognostication, this study aimed to define clinical risk factors for the
      development of severe acute pancreatitis. METHODS: Study design was a prospective
      cohort study, using multiple logistic regression. From March 2004 to July 2007,
      153 cases of acute pancreatitis were recruited in a regional Australian hospital.
      Data were collected regarding demographic and clinical characteristics. The
      outcome measure was severe acute pancreatitis, as defined by composite consensus
      criteria. RESULTS: After adjustment for potential confounders, there was a
      significant positive association with waist circumference and a negative
      association with current smoking status. CONCLUSION: The study confirms other
      work suggesting central adiposity as a risk factor for severe acute pancreatitis.
      The finding of a possible protective effect for smoking may be physiologically
      plausible but merits further confirmatory research.

PMID- 24103043
TI  - Acute haemodynamic effects of continuous positive airway pressure in awake
      patients with heart failure.
AB  - BACKGROUND AND OBJECTIVE: Continuous positive airway pressure (CPAP) has been
      used to treat patients with chronic heart failure (CHF) and sleep-disordered
      breathing (SDB). CPAP treatment in severe CHF with concomitant SDB and atrial
      fibrillation has been linked to impairment of cardiac output (CO) as a potential
      cause for adverse outcome. The aim of the present study was to test whether
      incremental CPAP application in awake CHF patients with SDB, with and without
      atrial fibrillation, induces acute alterations of blood pressure (BP), heart rate
      (HR) and CO. METHODS: During daytime, we applied incremental CPAP (4-10 cmH2O) in
      37 stable patients with CHF and SDB. BP and HR were assessed after each 1 cmH2O
      CPAP increase in 5-min intervals in the entire sample, and CO was assessed at one
      centre (n = 11). RESULTS: Neither mean BP, HR nor CO changed significantly with
      incremental CPAP (at 0 and 10 cmH2O: 85 +/- 2 and 84 +/- 2 mm Hg, P = 1.0, 63 +/-
      1 to 61 +/- 2 b.p.m., P = 0.88 and 2.03 +/- 0.5 and 2.35 +/- 0.8 L/min/m2 , P =
      0.92, respectively). No significant differences in maximum BP drop or HR drop
      between patients with sinus rhythm and atrial fibrillation were found. In 1 of 37
      patients, a prespecified event of haemodynamic compromise (drop of mean BP >15 mm
      Hg) without clinical signs occurred. CONCLUSIONS: These results contribute to the
      evidence that CPAP does not cause haemodynamic compromise in the vast majority of
      normotensive CHF patients with SDB.

PMID- 24103044
TI  - Four novel HLA alleles, DRB1*04:11:03, DRB1*10:05, DRB1*15:94 and DRB1*16:22,
      identified in Brazilian individuals.
AB  - Four novel human leucocyte antigen (HLA) class II alleles were identified by
      sequencing-based typing (SBT) and analysis of the closest-matching alleles from
      volunteer subjects from the Brazilian Bone Marrow Donor Register (REDOME,
      Brazil). The new HLA alleles discovered include DRB1*04:11:03, DRB1*10:05,
      DRB1*15:94 and DRB1*16:22. Three of the novel alleles had single-nucleotide
      substitution polymorphisms when compared to their most homologous allele. Of
      these, one harboured a single-nucleotide polymorphism (SNP) identified as a
      silent substitution. 

PMID- 24103045
TI  - Use of implementation theory: a focus on PARIHS.
AB  - BACKGROUND: Limited understanding and application of theory in implementation
      research contributes to variable effectiveness of implementation studies. Better
      understanding of direct experiences with theory could improve implementation
      research and the potency of interventions. AIMS: This study was a conceptual
      exercise aimed at characterizing experiences with and applications of the
      Promoting Action on Research Implementation in Health Services (PARIHS)
      framework. METHODS: This was a structured, qualitative study involving document
      reviews and interviews used to answer the following overarching questions about
      nine implementation research centers: Why and how was PARIHS used? What strengths
      and weaknesses were identified for PARIHS? FINDINGS: PARIHS was being used for
      varied purposes, at varied levels, in varied ways, and to a varying extent within
      and across centers. Lack of implementation theory use in investigators' early
      years was common. Variability in the nature of theory use was attributable to
      characteristics of the centers, individual investigators, and features of PARIHS.
      Strengths and weaknesses of the PARIHS framework were identified. LINKING
      EVIDENCE TO ACTION: The study provides information to researchers and theorists
      about the use of one well-known implementation framework. The information
      suggests areas for improvements in PARIHS as well as theory use in general, and
      should assist in the development of theory-based programs of research.

PMID- 24103046
TI  - Surgical treatment options for grafting areas of gingival recession association
      with cervical lesions: a review.
AB  - STATEMENT OF THE PROBLEM: Gingival recession (GR) is a highly prevalent dental
      problem that may be associated with dentin hypersensitivity and aesthetic
      complaint. Furthermore, GR is often complicated by dental cervical wear of
      substance, such as erosion, abrasion, or abfraction lesions, as well as initial
      or more extensive carious involvement of the cervical area, which worsen the
      symptoms and make the treatment of this periodontal condition more challenging.
      THE PURPOSE OF THE STUDY: To provide an overview of surgical treatment options
      presented in the literature for sites affected by GR with carious cervical
      lesions (CCLs) or non-carious cervical lesions (NCCLs). METHODS: The Medline
      database was searched for items dealing with GR and its treatment options,
      especially on GR associated with CCLs or NCCLs. RESULTS: Several periodontal
      surgical techniques have shown good potential for treating GR over the years.
      Specifically, considering GR associated with CCL or NCCL, an assessment of both
      hard (dental) and soft (gingival) tissue characteristics of the involved site is
      recommended in selecting the surgical procedure. CONCLUSIONS: For GR associated
      with CCL or NCCL, hard and soft tissue characteristics of the involved site have
      to be carefully evaluated in order to choose the most appropriate surgical
      procedure. CLINICAL SIGNIFICANCE: A structured decision-making process,
      considering both hard and soft tissue characteristics of the involved site, is
      recommended in choosing the most appropriate surgical procedures to treat GR
      associated with CCL or NCCL defects. The restitutio ad integrum of the dento
      periodontal unit is an essential condition to restore the tooth to its original
      function and esthetics.

PMID- 24103047
TI  - Imaging diagnosis--meningoencephalitis secondary to suppurative rhinitis and
      meningoencephalocele infection in a dog.
AB  - Nasal encephaloceles (meningoceles or meningoencephaloceles) are rare and not
      reported to be infected or coupled with a facial deformity in dogs. This report
      describes an older dog with acute worsening of seizures due to suppurative
      meningoencephalitis with coexisting suppurative rhinitis and infection of a
      meningoencephalocele. Additionally, the dog had a facial deformity for at least 5
      years. The results of necropsy, computed tomography, and postmortem magnetic
      resonance imaging are compared. The development of nasal encephaloceles is
      discussed, including the potential role of early trauma, and whether separation
      of neural ectoderm from the surface ectoderm is part of the pathogenesis. 

PMID- 24103048
TI  - Podoplanin is expressed at the invasive front of esophageal squamous cell
      carcinomas and is involved in collective cell invasion.
AB  - The expression of podoplanin is reportedly involved in collective cell invasion,
      which is independent from the epithelial-mesenchymal transition (EMT). We focused
      on the expression of podoplanin in esophageal squamous cell carcinomas (ESCC) and
      investigated the correlation of podoplanin and EMT-related markers, and evaluated
      its prognostic significance. Five ESCC cell lines were subjected to western blot
      analysis for podoplanin and EMT markers. The effects of podoplanin on EMT and
      carcinoma invasion were evaluated with wound healing assays, invasion assays and
      3-D culture. Transfection of ectopic podoplanin into a podoplanin-negative ESCC
      cell line (TE-15) induced cell migration and invasive activity (P < 0.001 and P <
      0.05, respectively) without downregulation of E-cadherin. In contrast,
      transfection of si-podoplanin RNA into a podoplanin-positive ESCC cell line (TE
      13) reduced cell migration and invasive activity (P < 0.05). We reviewed 101
      patients who had undergone esophagectomy for ESCC. Podoplanin expression was
      observed in 58 patients (57.4%), and positive expression was positively
      correlated with expression of E-cadherin (P < 0.01), deeper wall invasion (P <
      0.01), venous invasion (P < 0.05) and poorer prognosis (P < 0.01). Multivariate
      Cox analysis revealed that expression of podoplanin was a significant and
      independent unfavorable predictor of survival (P < 0.05). These data suggest that
      podoplanin is significantly associated with and likely contributes to ESCC
      invasion in the absence of EMT.

PMID- 24103049
TI  - Necroptosis in solid organ transplantation: a missing link to immune activation?

PMID- 24103050
TI  - The Achilles tendon of preventing BK virus nephropathy.

PMID- 24103051
TI  - Eliciting a policy response for the rising epidemic of overweight-obesity in
      India.
AB  - India is experiencing multiple transitions with respect to nutrition patterns,
      epidemiology and demography. Along with staggering childhood undernutrition, a
      rapid rise in chronic diseases and their risk factors including overweight
      obesity (O-O), among all sections of society, is compounding India's health
      challenges. We present an overview of the O-O scenario (prevalence, determinants)
      and profile existing initiatives to address this modifiable risk factor in India.
      Urgent attention from all sectors, committed resources, policy support and
      targeted actions are warranted to combat the dual burden of malnutrition. The
      health systems should be reoriented and strengthened, in addition to enabling
      actions in other sectors, to address prevention and control of non-communicable
      diseases and associated risk factors like O-O. 

PMID- 24103052
TI  - Selecting the most appropriate inferential statistical test for your quantitative
      research study.
AB  - AIMS AND OBJECTIVES: To discuss the issues and processes relating to the
      selection of the most appropriate statistical test. A review of the basic
      research concepts together with a number of clinical scenarios is used to
      illustrate this. BACKGROUND: Quantitative nursing research generally features the
      use of empirical data which necessitates the selection of both descriptive and
      statistical tests. Different types of research questions can be answered by
      different types of research designs, which in turn need to be matched to a
      specific statistical test(s). DESIGN: Discursive paper. METHODS: This paper
      discusses the issues relating to the selection of the most appropriate
      statistical test and makes some recommendations as to how these might be dealt
      with. CONCLUSION: When conducting empirical quantitative studies, a number of key
      issues need to be considered. Considerations for selecting the most appropriate
      statistical tests are discussed and flow charts provided to facilitate this
      process. RELEVANCE TO CLINICAL PRACTICE: When nursing clinicians and researchers
      conduct quantitative research studies, it is crucial that the most appropriate
      statistical test is selected to enable valid conclusions to be made.

PMID- 24103053
TI  - KNIME-CDK: Workflow-driven cheminformatics.
AB  - BACKGROUND: Cheminformaticians have to routinely process and analyse libraries of
      small molecules. Among other things, that includes the standardization of
      molecules, calculation of various descriptors, visualisation of molecular
      structures, and downstream analysis. For this purpose, scientific workflow
      platforms such as the Konstanz Information Miner can be used if provided with the
      right plug-in. A workflow-based cheminformatics tool provides the advantage of
      ease-of-use and interoperability between complementary cheminformatics packages
      within the same framework, hence facilitating the analysis process. RESULTS:
      KNIME-CDK comprises functions for molecule conversion to/from common formats,
      generation of signatures, fingerprints, and molecular properties. It is based on
      the Chemistry Development Toolkit and uses the Chemical Markup Language for
      persistence. A comparison with the cheminformatics plug-in RDKit shows that KNIME
      CDK supports a similar range of chemical classes and adds new functionality to
      the framework. We describe the design and integration of the plug-in, and
      demonstrate the usage of the nodes on ChEBI, a library of small molecules of
      biological interest. CONCLUSIONS: KNIME-CDK is an open-source plug-in for the
      Konstanz Information Miner, a free workflow platform. KNIME-CDK is build on top
      of the open-source Chemistry Development Toolkit and allows for efficient cross
      vendor structural cheminformatics. Its ease-of-use and modularity enables
      researchers to automate routine tasks and data analysis, bringing complimentary
      cheminformatics functionality to the workflow environment.

PMID- 24103054
TI  - Multilocus phylogeographic assessment of the California Mountain Kingsnake
      (Lampropeltis zonata) suggests alternative patterns of diversification for the
      California Floristic Province.
AB  - Phylogeographic inference can determine the timing of population divergence,
      historical demographic processes, patterns of migration, and when extended to
      multiple species, the history of communities. Single-locus analyses can mislead
      interpretations of the evolutionary history of taxa and comparative analyses. It
      is therefore important to revisit previous single-locus phylogeographic studies,
      particularly those that have been used to propose general patterns for regional
      biotas and the processes responsible for generating inferred patterns. Here, we
      employ a multilocus statistical approach to re-examine the phylogeography of
      Lampropeltis zonata. Using nonparametic and Bayesian species delimitation, we
      determined that there are two well-supported species within L. zonata. Ecological
      niche modelling supports the delimitation of these taxa, suggesting that the two
      species inhabit distinct climatic environments. Gene flow between the two taxa is
      low and appears to occur unidirectionally. Further, our data suggest that gene
      flow was mediated by females, a rare pattern in snakes. In contrast to previous
      analyses, we determined that the divergence between the two lineages occurred in
      the late Pliocene (c. 2.07 Ma). Spatially and temporally, the divergence of these
      lineages is associated with the inundation of central California by the Monterey
      Bay. The effective population sizes of the two species appear to have been
      unaffected by Pleistocene glaciation. Our increased sampling of loci for L.
      zonata, combined with previously published multilocus analyses of other sympatric
      species, suggests that previous conclusions reached by comparative
      phylogeographic studies conducted within the California Floristic Province should
      be reassessed.

PMID- 24103055
TI  - The magnetic anal sphincter in faecal incontinence: is initial success sustained
      over time?
AB  - AIM: In the short term, implantation of a magnetic anal sphincter (MAS) is a safe
      and effective treatment for faecal incontinence (FI). In this paper we show that
      the initial results stand the test of time and patient satisfaction remains high
      in the medium term. METHOD: Data on 23 women [median age 64 (35-78) years]
      implanted with a MAS device between December 2008 and September 2012 were
      reviewed from a prospective database. Assessment was based on significant
      improvement of incontinence scores - the Cleveland Clinic Florida Incontinence
      Severity (CCF-IS) score, Faecal Incontinence Quality of Life (FIQoL) score - and
      patient satisfaction at 6, 12, 24 and 36 months after surgery. RESULTS: The
      device was removed in two patients owing to complications. Median follow-up was
      17.6 months. The median preoperative CCF-IS score was 15.2 and fell to 6.9, 7.7,
      7.8 and 5.3 at 6, 12, 24 and 36 months, respectively. The median FIQoL score
      significantly (P < 0.001) improved from 1.97 preoperatively to 3.19, 3.11, 2.92
      and 2.93, respectively, at the same time periods. The concordance of the CCF-IS
      and FIQoL scores was 91%. Sixteen of the 23 patients were satisfied but only 14
      would have recommended the MAS to someone else. Lack of improvement was the main
      reason for dissatisfaction. CONCLUSION: Good initial results tend to remain
      stable over time and about two-thirds of patients are satisfied after MAS
      implantation.

PMID- 24103056
TI  - Electrophysiological properties of the superior vena cava and venoatrial junction
      in patients with atrial fibrillation: relevance to catheter ablation.
AB  - BACKGROUND: Although the superior vena cava (SVC) has been well known to be one
      of the important foci triggering atrial fibrillation (AF), its
      electrophysiological characteristics have received little research attention. The
      aim of this study was to investigate the electrophysiological properties of the
      SVC and venoatrial junction (VAJ). METHODS: Twenty-five consecutive AF patients
      without structural heart disease undergoing electrical SVC isolation were
      included in this study. After pulmonary vein isolation, a circular decapolar
      catheter and 2 multipolar catheters were emplaced in the VAJ, right atrial
      appendage (RAA), and SVC, respectively. Burst pacing and single extrastimulus
      were applied from the RAA and SVC. The atrial and caval potentials on the
      circular catheter in the VAJ were investigated. RESULTS: Intracaval conduction
      delay and various degrees of conduction block over the VAJ were observed with
      burst pacing from both the RAA and SVC. A single extrastimulus from the RAA and
      SVC with a basic cycle length of 600 milliseconds prolonged the conduction time
      via the VAJ by 81 +/- 49.7 milliseconds and 61 +/- 58.7 milliseconds,
      respectively. The atrial and caval electrograms at the VAJ, which were separated
      from each other by pacing applications, facilitated mapping of the earliest
      activation site at the VAJ. CONCLUSIONS: Intracaval conduction delay and
      decremental conduction property via the VAJ were demonstrated using pacing
      maneuvers. Pacing applications from the RAA or SVC can help distinguish the
      atrial and caval potentials and can facilitate mapping of the optimal ablation
      sites to isolate the SVC.

PMID- 24103057
TI  - The Northern Finland Birth Cohort Eye Study: Design and baseline characteristics.
AB  - BACKGROUND: To describe the rationale and design of the Northern Finland Birth
      Cohort (NFBC) Eye Study. METHODS: The NFBC Eye Study is a randomised prospective
      cohort study. The original NFBC study population consists of 12058 subjects born
      in the region of Lapland and the Province of Oulu. A postal questionnaire
      covering extensively the medical and socioeconomical background was sent to the
      10300 subjects of the NFBC alive and residing in Finland. For the NFBC eye study
      the subjects were randomised to the screening group (50%) and the control group
      (50%). The screening protocol includes the following tests: automated and
      manifest refraction, best corrected visual acuity, central corneal thickness,
      intraocular pressure, Humphrey 24-2 perimetry, stereoscopic optic nerve head
      (ONH) and retinal nerve fibre layer (RNFL) photography and imaging with Scanning
      Laser Ophthalmoscopy (HRT), Scanning Laser Polarimetry (GDx) and Optical
      Coherence Tomography (OCT).Two ophthalmologists evaluate the ONH and RNFL
      photographs and the visual fields independently. All suspected glaucoma cases are
      re-evaluated by two independent glaucoma experts. HRT, GDx and OCT findings are
      assessed separately. In the future, both groups (100%) will be examined. The
      effectiveness and the cost-effectiveness of glaucoma screening will be
      calculated. The response rate of the questionnaire was 67% (n = 6855) and 871
      randomised subjects had undergone the eye screening protocol by the end of April
      2013. DISCUSSION: The trial is designed to address the following questions: what
      is the best combination of diagnostic tests for detecting glaucoma in an
      unscreened population, what are the benefits and disadvantages of the screening
      to the individual and the society and is glaucoma screening both effective and
      cost-effective. The prevalence, incidence and risk factors of glaucoma and other
      eye diseases will be evaluated, as well as their impact on quality of life.

PMID- 24103058
TI  - Upregulation of axon guidance molecules in the adult central nervous system of
      Nogo-A knockout mice restricts neuronal growth and regeneration.
AB  - Adult central nervous system axons show restricted growth and regeneration
      properties after injury. One of the underlying mechanisms is the activation of
      the Nogo-A/Nogo receptor (NgR1) signaling pathway. Nogo-A knockout (KO) mice show
      enhanced regenerative growth in vivo, even though it is less pronounced than
      after acute antibody-mediated neutralization of Nogo-A. Residual inhibition may
      involve a compensatory component. By mRNA expression profiling and immunoblots we
      show increased expression of several members of the Ephrin/Eph and
      Semaphorin/Plexin families of axon guidance molecules, e.g. EphrinA3 and EphA4,
      in the intact spinal cord of adult Nogo-A KO vs. wild-type (WT) mice. EphrinA3
      inhibits neurite outgrowth of EphA4-positive neurons in vitro. In addition,
      EphrinA3 KO myelin extracts are less growth-inhibitory than WT but more than Nogo
      A KO myelin extracts. EphA4 KO cortical neurons show decreased growth inhibition
      on Nogo-A KO myelin as compared with WT neurons, supporting increased EphA4
      mediated growth inhibition in Nogo-A KO mice. Consistently, in vivo, Nogo-A/EphA4
      double KO mice show increased axonal sprouting and regeneration after spinal cord
      injury as compared with EphA4 KO mice. Our results reveal the upregulation of
      developmental axon guidance cues following constitutive Nogo-A deletion, e.g. the
      EphrinA3/EphA4 ligand/receptor pair, and support their role in restricting
      neurite outgrowth in the absence of Nogo-A. 

PMID- 24103059
TI  - Efficacy and side effects of praziquantel in the treatment for Schistosoma
      mansoni infection in school children in Senbete Town, northeastern Ethiopia.
AB  - OBJECTIVE: To assess the efficacy and side effects of praziquantel in the
      treatment for Schistosoma mansoni infection in school children in Senbete Town,
      northeastern Ethiopia. METHODS: A single stool specimen was collected from 342
      school children and examined for S. mansoni ova using Kato-Katz technique (single
      slide) and formol-ether concentration technique. Positive individuals were
      treated with a single oral dose of praziquantel at 40 mg/kg body weight. Egg
      reduction and cure rates were assessed 4 weeks post-treatment. Structured
      questionnaires were also used to collect pre-treatment and 24-h post-treatment
      signs and symptoms to assess side effects of the drug. RESULTS: Praziquantel
      reduced the egg rate by 79.46% and achieved a cure rate of 82.89% 4 weeks post
      treatment. 86.67% of the children presented at least one transient drug-related
      sign and symptom 24-h post-treatment. CONCLUSION: Praziquantel demonstrated
      sufficient efficacy against S. mansoni in Senbete Town, northeastern Ethiopia.
      Mild and transient signs and symptoms associated with therapy disappeared within
      24 h without specific treatment.

PMID- 24103060
TI  - Did hardening occur among smokers in England from 2000 to 2010?
AB  - AIMS: To assess trends in the prevalence of 'hardcore' smoking in England between
      2000 and 2010, and to examine associations between hardcore smoking and socio
      demographic variables. DESIGN: Secondary analysis of data from the United
      Kingdom's General Lifestyle Survey (GLF) and the Health Survey for England (HSE).
      SETTING: Households in England. PARTICIPANTS: Self-reported adult current smokers
      resident in England aged 26 years and over. MEASUREMENTS: Hardcore smokers were
      defined in three ways: smokers who do not want to quit (D1), those who 'usually'
      smoke their first cigarette of the day within 30 minutes of waking (D2) and a
      combination of D1 and D2, termed D3. Multivariable logistic regression was used
      to explore associations between these variables and calendar year, age, sex and
      socio-economic status, and P-values for trends in odds were calculated. FINDINGS:
      The odds of smokers being defined as hardcore according to D3 increased over time
      in both the GLF (P < 0.001) and HSE (P = 0.04), even after adjusting for risk
      factors. Higher dependence (D2) was noted in men [odds ratio (OR): 1.19, 95%
      confidence interval (CI): 1.13-1.24], those of 50-59 years (OR: 1.94, 95% CI:
      1.80-2.09) and smokers in lower occupational groups (OR: 2.11, 95% CI: (1.97
      2.26). Lack of motivation to quit (D1) increased with age and was more likely in
      men. CONCLUSIONS: The proportion of smokers in England with both low motivation
      to quit and high dependence appears to have increased between 2000 and 2010,
      independently of risk factors, suggesting that 'hardening' may be occurring in
      this smoker population.

PMID- 24103061
TI  - Measuring the evidence: reviewing the literature of the measurement of
      therapeutic engagement in acute mental health inpatient wards.
AB  - Quality nursing plays a central role in the delivery of contemporary health and
      social care, with a positive correlation being demonstrated between patient
      satisfaction and the quality of nursing care received. One way to ensure such
      quality is to develop metrics that measure the effectiveness of various aspects
      of care across a variety of settings. Effective mental health nursing is
      predicated on understanding the lived experiences of service users in order to
      provide sensitively-attuned nursing care. To achieve this, mental health nurses
      need to establish the all-important therapeutic relationship, showing compassion
      and creating a dialogue whereby service users feel comfortable to share their
      experiences that help contextualize their distress. Indeed, service users value
      positive attitudes, being listened to, and being able to trust those who provide
      care, while mental health nurses value their ability to relate through talking,
      listening, and expressing empathy. However, the literature suggests that within
      mental health practice, a disproportionate amount of time is taken up by other
      activities, with little time being spent listening and talking to service users.
      The present study discusses the evidence relating to the therapeutic relationship
      in acute mental health wards and explores why, after five decades, it is not
      recognized as a fundamental metric of mental health nursing. 

PMID- 24103062
TI  - Evaluation of paediatric nursing-sensitive outcomes in an Australian population
      using linked administrative hospital data.
AB  - BACKGROUND: Research into nursing-sensitive outcomes using administrative health
      data has focussed on hospitalised adults. However, we developed algorithms for
      the identification of 13 paediatric nursing-sensitive outcomes, which we seek to
      examine for clinical utility. The aims were to determine the rates of paediatric
      nursing-sensitive outcomes in a Western Australian hospital and ascertain
      sociodemographic and clinical characteristics associated with a greater risk of
      developing nursing-sensitive outcomes in hospitalised children. METHOD: A
      retrospective cohort study used linked administrative data of all Western
      Australian children <=18 years admitted to the only tertiary paediatric hospital
      in Perth between 1999 and 2009. Rates per 1,000 hospital separations and per
      10,000 patient days were calculated for the following nursing-sensitive outcomes:
      lower respiratory tract infection (LRTI), gastrointestinal (GI) infection,
      pneumonia, sepsis, arrest/shock/respiratory failure, central nervous system
      complication, central venous line infection, infectious disease, pressure ulcer,
      failure to rescue, surgical wound infection, physiologic/metabolic derangement,
      and postoperative cardiopulmonary complications. Poisson multiple regression
      models were fitted to estimate rate ratios (RR) and 95% confidence intervals (CI)
      for suspected risk factors. RESULTS: Linked records of 129,719 hospital
      separations were analysed. Rates ranged from 0.5/1,000 for pressure ulcer to
      14.0/1,000 hospital separations for GI infections. Age was significantly
      associated with the risk of a nursing-sensitive outcome: compared with
      adolescents, toddlers had greater risk of GI infection (RR 9.89; 95% CI 6.24,
      15.69); infants had 7.74 times greater risk of LRTI (95% CI 5.11, 11.75), while
      neonates had lower risks for sepsis (RR 0.26; 95% CI 0.08, 0.90) and
      physiologic/metabolic derangement (RR 0.12; 95% CI 0.04, 0.35). The risk of
      surgical wound infection was 7.78 times greater (95% CI 5.10, 11.86) for
      emergency admissions than elective admissions. CONCLUSIONS: Seven of the 13
      defined nursing-sensitive outcomes occurred with sufficient frequency (>100
      events over the 10 year study period) to be potentially useful for monitoring the
      quality of nursing care. These nursing-sensitive outcomes are: LRTI, GI
      infection, pneumonia, surgical wound infection, physiologic/metabolic
      derangement, sepsis and postoperative cardiopulmonary complications. When used
      for quality improvement or to benchmark with other agencies, data need to be
      adjusted for, or stratified by age and admission type, to ensure equitable
      comparisons.

PMID- 24103063
TI  - Radiographic and histopathologic characteristics of pulmonary fibrosis in nine
      cats.
AB  - Pulmonary fibrosis is a progressive fatal interstitial lung disease that is often
      idiopathic, occurs in multiple species, and may be caused by a number of inciting
      factors. The purpose of this retrospective, multicenter study was to describe the
      radiographic and histopathologic characteristics of idiopathic and induced
      pulmonary fibrosis in a group of cats. Cats with thoracic radiographs and
      histopathologically confirmed pulmonary fibrosis were recruited using the
      American College of Veterinary Radiology list serve. A board-certified veterinary
      radiologist and diagnostic imaging intern reviewed radiographs and recorded
      characteristics by consensus. Findings from additional imaging modalities were
      also recorded when available. All histopathology samples were re-reviewed by a
      veterinary pathology resident. A total of nine cats met inclusion criteria. All
      patients had a broad range of radiographic characteristics that included broncho
      interstitial pattern, alveolar pattern, pulmonary masses, pulmonary bullae,
      pleural effusion, and cardiomegaly. Cats with available echocardiographic studies
      had characteristics that included right ventricular dilation and hypertrophy and
      pulmonary arterial hypertension interpreted to be secondary to primary lung
      disease. Cats with available CT studies had characteristics that included focally
      increased soft tissue attenuation, masses, and ventral consolidation that
      exhibited no improvement with dorsal versus ventral recumbency. Histopathology
      showed pulmonary fibrosis, type II pneumocyte hyperplasia, and smooth muscle
      hypertrophy in all patients. Epithelial metaplasia was present only in one
      patient. Findings from the current study indicated that cats with pulmonary
      fibrosis have highly variable radiographic characteristics and that these
      characteristics may mimic other diseases such as asthma, pneumonia, pulmonary
      edema, or neoplasia. 

PMID- 24103064
TI  - Cardiac assessment in pediatric mice: strain analysis as a diagnostic
      measurement.
AB  - Echocardiography is a robust tool for assessing cardiac function in both humans
      and laboratory animals. Conventional echocardiographic measurements, including
      chamber dimensions, wall thickness, and ejection fraction are routinely obtained
      to assess cardiac function in mice. Recently, myocardial strain and strain rate
      measurements have been added to functional assessments to provide additional
      details on regional abnormalities that are not evident using conventional
      measurements. To date, all studies of strain and strain rate in mice or rats have
      involved adult animals. This study serves to outline methods for acquiring
      echocardiographic images in pediatric mice and to provide myocardial strain and
      strain rate values for healthy C57BL/6J mice between 3 and 11 weeks old. Between
      weeks 3 and 11, left ventricular radial strain ranged from 32 to 43% and
      longitudinal strain ranged from -15 to -19%, with analysis over time showing no
      significant changes with aging (radial strain, P = 0.192 and longitudinal strain,
      P = 0.264; n = 4 for each time point evaluated). In conclusion, myocardial strain
      analysis in pediatric mice is technically feasible and has potential application
      in studying the pathophysiology of pediatric cardiovascular disease.

PMID- 24103065
TI  - MBL2 polymorphisms - manifestations in Bulgarian patients with adult
      dermatomyositis and systemic lupus erythematosus.
AB  - Deficiency in some complement factors is known to cause both systemic lupus
      erythematosus (SLE) and dermatomyositis (DM). Mannose-binding lectin (MBL) is a
      recognition molecule of the lectin pathway, and its low levels are reported to
      influence some autoimmune diseases. Furthermore, MBL2 polymorphisms have been
      described associated with low MBL serum levels due to impaired MBL structure and
      function. This is a pilot study to investigate the role of MBL2-550G/C (H/L), 
      221G/C (Y/X), Arg52Cys (D), Gly54Asp (B), Gly57Glu (C) polymorphisms and MBL
      serum levels as a risk factor for a development of adult DM and SLE in Bulgarian
      patients. None of the studied MBL2 polymorphisms appeared associated with the
      diseases investigated. However, we have found an increased OR of MBL2-221XY
      genotype in the patients with SLE (OR 1.64, 95%CI 0.77-3.52). MBL2 polymorphisms
      seemed to affect MBL serum levels and to be associated with the clinical features
      although none of the associations remained statistically significant after
      Bonferroni correction. The-550L allele showed an association with
      electromyography findings in patients with DM. The-221XY genotype was associated
      with photosensitivity in patients with SLE. The 54AB genotype showed an
      association with malar rash in patients with SLE, but it appeared decreased among
      SLE patients with ANA. In conclusion, our results suggest that the MBL2
      polymorphisms have rather a disease modifying role and they are not associated
      with the disease susceptibility in adult DM and SLE among Bulgarian patients. 

PMID- 24103066
TI  - Evaluation of the radiopacity of esthetic root canal posts.
AB  - The radiopacity of esthetic root canal posts may impair the assessment of their
      fit to the root canal when using radiographic images. This study determined in
      vitro the radiographic density of esthetic root canal posts using digital images.
      Thirty-six roots of human maxillary canines were assigned to six groups (N=6 per
      group): Reforpost (RP); Aestheti-Plus (AP); Reforpost MIX (RPM); D.T. Light Post
      (LP); Reforpost Radiopaque (RPR); and White Post DC (WP). Standardized digital
      images of the posts were obtained in different conditions: outside the root
      canal, inside the canal before and after cementation using luting material, and
      with a tissue simulator. Analysis of variance was used to compare the radiopacity
      mean values among the posts outside the root canal and among the posts under the
      other conditions, and the "t" unpaired test to compare the radiopacity between
      the posts and the dentin, and between the posts and the root canal space. There
      was no statistically significant difference in radiopacity between RP and RPM,
      and LP and WP. AP posts showed radiopacity values significantly lower than those
      for dentin. No statistically significant difference was found between posts (RP
      and AP) and the root canal space. A statistically significant difference was
      observed between the luted and non-luted posts; additionally, luted posts with
      and without tissue simulator showed no significant differences. Most of the
      cement-luted posts analyzed in this study were distinguishable from the density
      of adjacent dentin surfaces, allowing radiographic confirmation of the fit of the
      post in the canal. CLINICAL SIGNIFICANCE: The success of using esthetic root
      canal posts depends mainly on the fit of the post within the canal.[1] The
      radiopacity of a post allows for radiographic imaging to be used to determine the
      fit, an important factor in a clinical perspective.

PMID- 24103067
TI  - Loss-of-function of OsSTN8 suppresses the photosystem II core protein
      phosphorylation and interferes with the photosystem II repair mechanism in rice
      (Oryza sativa).
AB  - STN8 kinase is involved in photosystem II (PSII) core protein phosphorylation
      (PCPP). To examine the role of PCPP in PSII repair during high light (HL)
      illumination, we characterized a T-DNA insertional knockout mutant of the rice
      (Oryza sativa) STN8 gene. In this osstn8 mutant, PCPP was significantly
      suppressed, and the grana were thin and elongated. Upon HL illumination, PSII was
      strongly inactivated in the mutants, but the D1 protein was degraded more slowly
      than in wild-type, and mobilization of the PSII supercomplexes from the grana to
      the stromal lamellae for repair was also suppressed. In addition, higher
      accumulation of reactive oxygen species and preferential oxidation of PSII
      reaction center core proteins in thylakoid membranes were observed in the mutants
      during HL illumination. Taken together, our current data show that the absence of
      STN8 is sufficient to abolish PCPP in osstn8 mutants and to produce all of the
      phenotypes observed in the double mutant of Arabidopsis, indicating the essential
      role of STN8-mediated PCPP in PSII repair.

PMID- 24103068
TI  - Development and validation of the Pediatric Anesthesia Behavior score--an
      objective measure of behavior during induction of anesthesia.
AB  - BACKGROUND: Measuring perioperative behavior changes requires validated objective
      rating scales. We developed a simple score for children's behavior during
      induction of anesthesia (Pediatric Anesthesia Behavior score) and assessed its
      reliability, concurrent validity, and predictive validity. METHODS: Data were
      collected as part of a wider observational study of perioperative behavior
      changes in children undergoing general anesthesia for elective dental
      extractions. One-hundred and two healthy children aged 2-12 were recruited.
      Previously validated behavioral scales were used as follows: the modified Yale
      Preoperative Anxiety Scale (m-YPAS); the induction compliance checklist (ICC);
      the Pediatric Anesthesia Emergence Delirium scale (PAED); and the Post
      Hospitalization Behavior Questionnaire (PHBQ). Pediatric Anesthesia Behavior
      (PAB) score was independently measured by two investigators, to allow assessment
      of interobserver reliability. Concurrent validity was assessed by examining the
      correlation between the PAB score, the m-YPAS, and the ICC. Predictive validity
      was assessed by examining the association between the PAB score, the PAED scale,
      and the PHBQ. RESULTS: The PAB score correlated strongly with both the m-YPAS (P
      < 0.001) and the ICC (P < 0.001). PAB score was significantly associated with the
      PAED score (P = 0.031) and with the PHBQ (P = 0.034). Two independent
      investigators recorded identical PAB scores for 94% of children and overall,
      there was close agreement between scores (Kappa coefficient of 0.886 [P <
      0.001]). CONCLUSION: The PAB score is simple to use and may predict which
      children are at increased risk of developing postoperative behavioral
      disturbance. This study provides evidence for its reliability and validity.

PMID- 24103069
TI  - Phenotypical properties associated with virulence from clinical isolates
      belonging to the Candida parapsilosis complex.
AB  - The production of virulence attributes in three reference strains and 11 clinical
      isolates primarily identified as Candida parapsilosis was evaluated.
      Morphological and phenotypical tests were not able to discriminate among the
      three species of the C. parapsilosis complex; consequently, molecular methods
      were applied to solve this task. After employing polymerase chain reaction-based
      methods, nine clinical strains were identified as C. parapsilosis sensu stricto
      and two as C. orthopsilosis. Protease, catalase, and hemolysin were produced by
      all 14 strains, while 92.9% and 78.6% of strains secreted, respectively, esterase
      and phytase. No phospholipase producers were detected. Mannose/glucose, N
      acetylglucosamine, and sialic acid residues were detected at the surface of all
      strains, respectively, in high, medium, and low levels. All strains presented
      elevated surface hydrophobicity and similar ability to form biofilm. However, the
      adhesion to inert substrates and mammalian cells was extremely diverse, showing
      typical intrastrain variations. Overall, the strains showed (1) predilection to
      adhere to plastic over glass and the number of pseudohyphae was more prominent
      than yeasts and (2) the interaction process was slightly enhanced in macrophages
      than fibroblasts, with the majority of fungal cells detected inside them.
      Positive/negative correlations were demonstrated among the production of these
      virulence traits in C. parapsilosis complex.

PMID- 24103070
TI  - Time-scale separation--Michaelis and Menten's old idea, still bearing fruit.
AB  - Michaelis and Menten introduced to biochemistry the idea of time-scale
      separation, in which part of a system is assumed to be operating sufficiently
      fast compared to the rest so that it may be taken to have reached a steady state.
      This allows, in principle, the fast components to be eliminated, resulting in a
      simplified description of the system's behaviour. Similar ideas have been widely
      used in different areas of biology, including enzyme kinetics, protein allostery,
      receptor pharmacology, gene regulation and post-translational modification.
      However, the methods used have been independent and ad hoc. In the present study,
      we review the use of time-scale separation as a means to simplify the description
      of molecular complexity and discuss recent work setting out a single framework
      that unifies these separate calculations. The framework offers new capabilities
      for mathematical analysis and helps to do justice to Michaelis and Menten's
      insights about individual enzymes in the context of multi-enzyme biological
      systems. 

PMID- 24103071
TI  - Transitional cell carcinoma in a renal allograft with BK nephropathy.

PMID- 24103073
TI  - A food policy package for healthy diets and the prevention of obesity and diet
      related non-communicable diseases: the NOURISHING framework.
AB  - This paper presents the NOURISHING framework of food policies to promote healthy
      diets, and uses the framework to summarize the policy actions taken by the
      Bellagio meeting countries. NOURISHING was developed by WCRF International to
      formalize a comprehensive policy package that brings together the key domains of
      action and policy areas. It aims to provide global level recommendations for a
      comprehensive response, within which policymakers have the flexibility to select
      specific policy options suitable for their national/local contexts and target
      populations. It also aims to provide a framework for reporting, categorizing and
      monitoring policy actions taken around the world, and for systematically
      categorizing, updating, interpreting and communicating the evidence for policy to
      policymakers. In this paper we explain the structure for NOURISHING and the
      rationale behind it. We also use the framework to report on and categorize the
      policy actions implemented in the Bellagio countries. 

PMID- 24103072
TI  - Long-term exposure to belatacept in recipients of extended criteria donor
      kidneys.
AB  - Patients in the BENEFIT-EXT study received extended criteria donor kidneys and a
      more intensive (MI) or less intensive (LI) belatacept immunosuppression regimen,
      or cyclosporine A (CsA). Patients who remained on assigned therapy through year 3
      were eligible to enter a long-term extension (LTE) study. Three hundred four
      patients entered the LTE (n = 104 MI; n = 113 LI; n = 87 CsA), and 260 continued
      treatment through year 5 (n = 91 MI; n = 100 LI; n = 69 CsA). Twenty patients
      died during the LTE (n = 5 MI; n = 9 LI; n = 6 CsA), and eight experienced graft
      loss (n = 2 MI; n = 1 LI; n = 5 CsA). Three patients experienced an acute
      rejection episode (n = 2 MI; n = 1 LI). The incidence rate of serious adverse
      events, viral infections and fungal infections was similar across groups during
      the LTE. There were four cases of posttransplant lymphoproliferative disorder
      (PTLD) from the beginning of the LTE to year 5 (n = 3 LI; n = 1 CsA); two of
      three PTLD cases in the LI group were in patients who were seronegative for
      Epstein-Barr virus (EBV(-)) at transplantation. Mean +/- SD calculated GFR at
      year 5 was 55.9 +/- 17.5 (MI), 59.0 +/- 29.1 (LI) and 44.6 +/- 16.4 (CsA)
      mL/min/1.73 m(2) . Continued treatment with belatacept was associated with a
      consistent safety profile and sustained improvement in renal function versus CsA
      over time. 

PMID- 24103074
TI  - Towards the development of a gender-sensitive measure of women's mental health.
AB  - AIMS AND OBJECTIVES: To develop a gender-sensitive measure of women's mental
      health and to evaluate the measure's psychometric properties. BACKGROUND: Mental
      health problems are a leading global burden of disease, and gender differences in
      the prevalence of these problems are well documented. Improving mental health is
      as important as resolving mental health problems. Although many mental health
      scales have been developed, few measure women's positive mental health from a
      gender perspective. DESIGN: Instrument development and psychometric evaluation
      were used. METHODS: First, a new mental health scale (Women's Mental Health
      Scale) grounded in women's subjective experiences was formulated from the
      narratives of four female focus groups (n = 23). The new scale was evaluated
      using principal component analysis and internal consistency reliability in a
      sample of female participants (n = 106). Next, the Women's Mental Health Scale,
      the Chinese version of Beck Depression Inventory-II and Social Adjustment Scale
      Self-Report were used in a survey of female undergraduate students (n = 163) for
      examining the concurrent criterion-related validity. Finally, gender differences
      were examined by assessing the discriminated validity of the Women's Mental
      Health Scale in a sample of male and female undergraduate students (n = 357). All
      participants were recruited from communities and universities in middle and south
      Taiwan. RESULTS: A 50-item Women's Mental Health Scale with four concepts of
      self, interpersonal, family and social domains was developed. It revealed that
      the Women's Mental Health Scale had acceptable psychometric properties. There was
      a significant negative correlation between scores of the Women's Mental Health
      Scale and the Chinese version of Beck Depression Inventory-II and a significant
      positive correlation between scores of the Women's Mental Health Scale and Social
      Adjustment Scale Self-Report. There were significant gender differences in the
      family domain and social domain. Women reported greater mental health in the
      family domain and social domain than men. CONCLUSIONS: The Women's Mental Health
      Scale is a promising gender-sensitive tool to measure women's mental health.
      RELEVANCE TO CLINICAL PRACTICE: The Women's Mental Health Scale appears to be a
      gender-sensitive measure to assess the positive mental health potentials among
      women population.

PMID- 24103075
TI  - An irregular rhythm in a patient with ventricular preexcitation: what is the
      mechanism?

PMID- 24103076
TI  - Factors related to lymph node harvest: does a recovery of more than 12 improve
      the outcome of colorectal cancer?
AB  - AIM: The nodal harvest was studied to identify factors that affected the number
      of lymph nodes (LNs) retrieved in patients undergoing curative surgery for
      colorectal cancer. The influence of predictive factors on overall and disease
      free 5-year survival was analysed. METHOD: All patients diagnosed with colorectal
      cancer who underwent oncological resection consecutively from January 1996 to
      December 2011 in a single institution have been studied. Factors influencing LN
      retrieval were analysed. A logistic regression analysis was performed to
      determine the factors that predicted a recovery of more than 12 LNs. A Cox
      regression analysis was made to identify the predictive factors of overall and
      disease-free 5-year survival. RESULTS: A total of 1166 patients were included in
      the study. The factors associated with the number of LNs harvested in surgical
      resections were age, colorectal surgeon, right colectomy, total colectomy, year
      of surgery, number of LN metastases and lymphocyte response. The factors that
      predicted a recovery of >= 12 LNs were age < 60 years, right colectomy, year of
      surgery and expert pathologist. A recovery of >= 12 LNs did not show significant
      differences in overall and disease-free 5-year survival, but the factor of
      colorectal surgeon did. CONCLUSION: Number of LN metastases, lymphocyte response,
      type of surgical resection, age of patient and colorectal surgeon can predict the
      LN harvest. Survival in colorectal cancer, however, is probably more influenced
      by the performance of the operation by an expert surgeon than by recovery of more
      than 12 LNs.

PMID- 24103077
TI  - A Hidden Markov Model for identifying essential and growth-defect regions in
      bacterial genomes from transposon insertion sequencing data.
AB  - BACKGROUND: Knowledge of which genes are essential to the survival of an organism
      is critical to understanding the function of genes, and for the identification of
      potential drug targets for antimicrobial treatment. Previous statistical methods
      for assessing essentiality based on sequencing of tranposon libraries have
      usually limited their assessment to strict 'essential' or 'non-essential'
      categories. However, this binary view of essentiality does not accurately
      represent the more nuanced ways the growth of an organism might be affected by
      the disruption of its genes. In addition, these methods often limit their
      analysis to open-reading frames. We propose a novel method for analyzing sequence
      data from transposon mutant libraries using a Hidden Markov Model (HMM), along
      with formulas to adapt the parameters of the model to different datasets for
      robustness. This approach allows for the clustering of insertion sites into
      distinct regions of essentiality across the entire genome in a statistically
      rigorous manner, while also allowing for the detection of growth-defect and
      growth-advantage regions. RESULTS: We evaluate the performance of a 4-state HMM
      on a sequence dataset of M. tuberculosis transposon mutants. We also test the HMM
      on several synthetic datasets representing different levels of transposon
      insertion density and sequence coverage. We show that the HMM produces results
      that are highly correlated with previous assignments of essentiality for this
      organism. We also show that it detects growth-defect and growth-advantage genes
      previously shown to impair or enhance growth when disrupted. CONCLUSIONS: A 4
      state HMM provides an improved way of analyzing Tn-seq data and assessing
      different levels of essentiality that enables not only the characterization of
      essential and non-essential genes, but also genes whose disruption leads to
      impairment (or enhancement) of growth.

PMID- 24103078
TI  - Intra-cardiac thrombus resolution after anti-coagulation therapy with dabigatran
      in a patient with mid-ventricular obstructive hypertrophic cardiomyopathy: a case
      report.
AB  - INTRODUCTION: Although dabigatran, a novel oral anti-coagulant, has been approved
      for the prevention of thromboembolism in patients with non-valvular atrial
      fibrillation, the efficacy of dabigatran for the resolution of established intra
      cardiac thrombi has not been validated. Herein is describe a case in which
      dabigatran was effective for thrombus resolution in a patient with a left
      ventricular aneurysm. CASE PRESENTATION: A 59-year-old Japanese man with a mid
      ventricular obstructive hypertrophic cardiomyopathy-associated apical aneurysm
      presented with a left ventricular apical thrombus (15.0mm*17.0mm). Anti
      coagulation therapy with dabigatran (150mg b.i.d. with meals) was initiated.
      Following dabigatran administration, weekly echocardiographic examinations
      demonstrated gradual decreases in thrombus size. After three weeks, no thrombus
      was detected and no systemic thromboembolic events had occurred. CONCLUSIONS: The
      left ventricular apical thrombus resolved after dabigatran administration. Hence,
      dabigatran may represent an alternative to warfarin as a therapeutic option in
      patients with previously detected intra-cardiac thrombus.

PMID- 24103079
TI  - Anti-CEA-functionalized superparamagnetic iron oxide nanoparticles for examining
      colorectal tumors in vivo.
AB  - Although the biomarker carcinoembryonic antigen (CEA) is expressed in colorectal
      tumors, the utility of an anti-CEA-functionalized image medium is powerful for in
      vivo positioning of colorectal tumors. With a risk of superparamagnetic iron
      oxide nanoparticles (SPIONPs) that is lower for animals than other material
      carriers, anti-CEA-functionalized SPIONPs were synthesized in this study for
      labeling colorectal tumors by conducting different preoperatively and
      intraoperatively in vivo examinations. In magnetic resonance imaging (MRI), the
      image variation of colorectal tumors reached the maximum at approximately 24 h.
      However, because MRI requires a nonmetal environment, it was limited to
      preoperative imaging. With the potentiality of in vivo screening and
      intraoperative positioning during surgery, the scanning superconducting-quantum
      interference-device biosusceptometry (SSB) was adopted, showing the favorable
      agreement of time-varied intensity with MRI. Furthermore, biological
      methodologies of different tissue staining methods and inductively coupled plasma
      (ICP) yielded consistent results, proving that the obtained in vivo results
      occurred because of targeted anti-CEA SPIONPs. This indicates that developed anti
      CEA SPIONPs owe the utilities as an image medium of these in vivo methodologies. 

PMID- 24103081
TI  - High-throughput amplicon sequencing of rRNA genes requires a copy number
      correction to accurately reflect the effects of management practices on soil
      nematode community structure.
AB  - Nematodes are abundant consumers in grassland soils, but more sensitive and
      specific methods of enumeration are needed to improve our understanding of how
      different nematode species affect, and are affected by, ecosystem processes. High
      throughput amplicon sequencing is used to enumerate microbial and invertebrate
      communities at a high level of taxonomic resolution, but the method requires
      validation against traditional specimen-based morphological identifications. To
      investigate the consistency between these approaches, we enumerated nematodes
      from a 25-year field experiment using both morphological and molecular
      identification techniques in order to determine the long-term effects of annual
      burning and nitrogen enrichment on soil nematode communities. Family-level
      frequencies based on amplicon sequencing were not initially consistent with
      specimen-based counts, but correction for differences in rRNA gene copy number
      using a genetic algorithm improved quantitative accuracy. Multivariate analysis
      of corrected sequence-based abundances of nematode families was consistent with,
      but not identical to, analysis of specimen-based counts. In both cases,
      herbivores, fungivores and predator/omnivores generally were more abundant in
      burned than nonburned plots, while bacterivores generally were more abundant in
      nonburned or nitrogen-enriched plots. Discriminate analysis of sequence-based
      abundances identified putative indicator species representing each trophic group.
      We conclude that high-throughput amplicon sequencing can be a valuable method for
      characterizing nematode communities at high taxonomic resolution as long as rRNA
      gene copy number variation is accounted for and accurate sequence databases are
      available. 

PMID- 24103080
TI  - Study protocol: the Childhood to Adolescence Transition Study (CATS).
AB  - BACKGROUND: Puberty is a multifaceted developmental process that begins in late
      childhood with a cascade of endocrine changes that ultimately lead to sexual
      maturation and reproductive capability. The transition through puberty is marked
      by an increased risk for the onset of a range of health problems, particularly
      those related to the control of behaviour and emotion. Early onset puberty is
      associated with a greater risk of cancers of the reproductive tract and
      cardiovascular disease. Previous studies have had methodological limitations and
      have tended to view puberty as a unitary process, with little distinction between
      adrenarche, gonadarche and linear growth. The Childhood to Adolescence Transition
      Study (CATS) aims to prospectively examine associations between the timing and
      stage of the different hormonally-mediated changes, as well as the onset and
      course of common health and behavioural problems that emerge in the transition
      from childhood to adolescence. The initial focus of CATS is on adrenarche, the
      first hormonal process in the pubertal cascade, which begins for most children at
      around 8 years of age. METHODS/DESIGN: CATS is a longitudinal population-based
      cohort study. All Grade 3 students (8-9 years of age) from a stratified cluster
      sample of schools in Melbourne, Australia were invited to take part. In total,
      1239 students and a parent/guardian were recruited to participate in the study.
      Measures are repeated annually and comprise student, parent and teacher
      questionnaires, and student anthropometric measurements. A saliva sample was
      collected from students at baseline and will be repeated at later waves, with the
      primary purpose of measuring hormonal indices of adrenarche and gonadarche.
      DISCUSSION: CATS is uniquely placed to capture biological and phenotypic indices
      of the pubertal process from its earliest manifestations, together with
      anthropometric measures and assessment of child health and development. The
      cohort will provide rich detail of the development, lifestyle, external
      circumstances and health of children during the transition from childhood through
      to adolescence. Baseline associations between the hormonal measures and measures
      of mental health and behaviour will initially be examined cross-sectionally, and
      then in later waves longitudinally. CATS will make a unique contribution to the
      understanding of adrenarche and puberty in children's health and development.

PMID- 24103082
TI  - Healthcare provision for HIV co-infected tuberculosis patients in rural Zambia:
      an observational cohort study at primary care centers.
AB  - BACKGROUND: Linkage of healthcare services for tuberculosis (TB) and human
      immunodeficiency virus (HIV) remains a major challenge in resource-limited
      settings. Our operational research aimed to evaluate the linkage between TB and
      HIV services in a rural area of Zambia, and to explore factors associated with
      the enrolment of TB/HIV co-infected patients in HIV care services. METHODS: All
      TB patients newly diagnosed as HIV-positive in Chongwe district, Zambia between
      2009 and 2010 were included. Data from TB registers and medical records were
      reviewed. Patient referral to HIV services and provision of antiretroviral
      therapy (ART) were further examined through HIV registers and records. RESULTS:
      Of 621 patients (median age 33.0 years, female 42.4%) who started anti-TB
      treatment, clinic records indicated that 297 patients were newly diagnosed as HIV
      positive, and 176 (59.3%) of these were referred to an ART clinic. Analysis of
      records at the ART clinic found that only 85 (28.6%) of TB/HIV patients had
      actually been enrolled in HIV care, of whom only 58 (68.2%) had commenced ART.
      Logistic regression analyses demonstrated the following factors associated with
      lower enrolment: "male" sex (aOR, 0.45; 95% CI 0.26-0.78), "previous TB
      treatment" (aOR, 0.29; 95% CI, 0.11-0.75), "registration at sites that did not
      provide ART services (non-ART site)" (aOR, 0.10; 95% CI, 0.01-0.77) and "death on
      TB treatment outcome (aOR, 0.20; 95% CI, 0.06-0.65). However, patient
      registration at TB clinics in 2010 was associated with markedly higher enrolment
      in HIV care as compared to registration in 2009 (aOR, 2.80; 95% CI, 1.53-5.12).
      CONCLUSIONS: HIV testing for TB patients has been successfully scaled up. However
      referrals of co-infected patients still remain a challenge due to poor linkage
      between TB and HIV healthcare services. Committed healthcare workers, a well
      organized health services system and patient education are urgently required to
      ensure a higher rate of referral of TB/HIV co-infected patients for appropriate
      care.

PMID- 24103084
TI  - Imaging diagnosis-hypoglycemia associated with cholangiocarcinoma and peritoneal
      carcinomatosis in a horse.
AB  - An 8-year-old Thoroughbred mare presented for decreased appetite, ataxia, and
      weakness. Abdominal ultrasound revealed a large volume of anechoic fluid along
      with multiple masses involving the spleen, liver, and diaphragm. Pleural fluid
      was identified via ultrasonography and thoracic radiography. Thoracic radiographs
      also identified pulmonary interstitial nodules, an undulant dorsal diaphragmatic
      margin and enlargement of tracheobronchial lymph nodes. Clinical signs of
      weakness and mild seizures were concurrent with hypoglycemic episodes. The final
      diagnosis was cholangiocarcinoma with extensive metastasis. Clinical signs of
      weakness, ataxia, and seizures were attributed to a paraneoplastic syndrome of
      tumor-associated hypoglycemia that has been infrequently reported in horses. 

PMID- 24103085
TI  - Does estimated glomerular filtration rate have an effect on left ventricular
      function after ST-elevation myocardial infarction?
AB  - OBJECTIVES: Little is known about whether estimated glomerular filtration rates
      (eGFR) affect left ventricular (LV) function and gain benefit with antiremodeling
      treatment in patients with ST-elevation myocardial infarction (STEMI). We
      investigated the effect of eGFR on LV function using tissue Doppler imaging (TDI)
      parameters. In addition, we sought to evaluate the antiremodeling effect of
      standard treatment at follow-up in patients with renal insufficiency (RI) after
      STEMI. METHODS AND RESULTS: A retrospective analysis of 579 patients with STEMI
      was performed. Patients were divided into 3 groups according to eGFR (Group 1:
      eGFR > 90 mL/min per 1.73 m(2); Group 2: eGFR = 60-89 mL/min per 1.73 m(2); Group
      3: eGFR < 60 mL/min per 1.73 m(2)). Conventional echocardiography and TDI were
      performed within 48-72 hours after STEMI and at 6-month follow-up. The mean left
      ventricular ejection fraction (LVEF) was significantly lower in Group 3 than in
      Group 1 (P = 0.021). The mean peak systolic velocity (Sm) was significantly lower
      in Group 3 than in Group 1 and Group 2 (P = 0.002 and 0.006, respectively). The
      estimated GFR had a linear association with Sm and LVEF (P = 0.001, r = 0.161; P
      = 0.005, r = 0.132, respectively). Multivariate analysis showed that an eGFR < 60
      mL/min per 1.73 m(2) was an independent predictor of lower Sm and in-hospital
      mortality. In addition, an antiremodeling effect of standard treatment was seen
      in all groups at 6-month follow-up. CONCLUSIONS: Estimated glomerular filtration
      rate of <60 mL/min per 1.73 m(2) was associated with lower LV function after
      STEMI, and may gain an antiremodeling effect with standard treatment at follow
      up.

PMID- 24103083
TI  - Comparing actual and perceived causes of fever among community members in a low
      malaria transmission setting in northern Tanzania.
AB  - OBJECTIVE: To compare actual and perceived causes of fever in northern Tanzania.
      METHODS: In a standardised survey, heads of households in 30 wards in Moshi,
      Tanzania, were asked to identify the most common cause of fever for children and
      for adults. Responses were compared to data from a local hospital-based fever
      aetiology study that used standard diagnostic techniques. RESULTS: Of 810
      interviewees, the median (range) age was 48 (16, 102) years and 509 (62.8%) were
      women. Malaria was the most frequently identified cause of fever, cited by 353
      (43.6%) and 459 (56.7%) as the most common cause of fever for children and
      adults, respectively. In contrast, malaria accounted for 8 (2.0%) of adult and 6
      (1.3%) of paediatric febrile admissions in the fever aetiology study. Weather was
      the second most frequently cited cause of fever. Participants who identified a
      non-biomedical explanation such as weather as the most common cause of fever were
      more likely to prefer a traditional healer for treatment of febrile adults (OR
      2.7, P < 0.001). Bacterial zoonoses were the most common cause of fever among
      inpatients, but no interviewees identified infections from animal contact as the
      most common cause of fever for adults; two (0.2%) identified these infections as
      the most common cause of fever for children. CONCLUSIONS: Malaria is perceived to
      be a much more common cause of fever than hospital studies indicate, whereas
      other important diseases are under-appreciated in northern Tanzania. Belief in
      non-biomedical explanations of fever is common locally and has important public
      health consequences.

PMID- 24103086
TI  - Fracture resistance of premolar teeth restored with silorane-based or
      dimethacrylate-based composite resins.
AB  - STATEMENT OF PROBLEM: To restore posterior teeth using low-shrinkage composite to
      minimize microleakage. PURPOSE: To compare the fracture resistance of mesio
      occlusal-distal (MOD) cavity preparations restored with either low-shrinkage
      composite or with dimethacrylate-based composite in conjunction with cavity
      liners and without them. The null hypothesis of the study is that there are no
      differences in either fracture resistance or fracture mode between the silorane
      group and dimethacrylate groups with and without the use of cavity liners. METHOD
      AND MATERIALS: Sixty maxillary premolars were divided into six groups of 10. MOD
      cavities were prepared in four groups: F: posterior composite (Filtek P60); GF:
      0.5-mm Glass Ionomer (Fuji LC) + posterior composite; FF: 0.5-mm flowable
      composite (Filtek Supreme XT) + posterior composite; and S: low-shrinkage
      composite (Filtek P90). Negative (N) and positive (P) control groups consisted of
      unrestored and sound teeth, respectively. The specimens were thermocycled and
      loaded. Data were analyzed using analysis of variance, Tukey, and chi-square
      tests (alpha = 0.05). RESULTS: Groups FF (1643.09 +/- 187/80 N) and GF (1596.80
      +/- 163/93 N) (p = 0.06 > 0.05) were statistically identical, although less than
      group P (1742/33 +/- 110/08 N), but still demonstrated greater fracture
      resistance than the other groups. The fracture resistance of group S (1434/69 +/-
      107/62 N) was identical to GF and FF (p = 0.06 > 0.05). The fracture resistance
      of F (1353/19 +/- 233/90 N) was less than GF and FF, and statistically identical
      to S (p = 0.87 > 0.05). CONCLUSION: Silorane-based composite showed a resistance
      to fracture similar to methacrylate-based composite restorations regardless of
      whether cavity liners were used. CLINICAL SIGNIFICANCE: The findings of this
      study support the selection of silorane-based composite for the restoration of
      maxillary premolars with standardized Class II cavity preparations in order to
      strengthen the resistance to fracture to the same extent as do dimethacrylate
      composites using cavity liners or without them.

PMID- 24103087
TI  - Training family members to manage heroin overdose and administer naloxone:
      randomized trial of effects on knowledge and attitudes.
AB  - AIMS: To evaluate a heroin overdose management training programme for family
      members based on emergency recovery procedures and take-home naloxone (THN)
      administration. DESIGN: A two-group, parallel-arm, non-blinded, randomized
      controlled trial of group-based training versus an information-only control.
      SETTING: Training events delivered in community addiction treatment services in
      three locations in England. PARTICIPANTS: A total of 187 family members and
      carers allocated to receive either THN training or basic information on opioid
      overdose management (n = 95 and n = 92, respectively), with 123 participants
      completing the study. MEASUREMENTS: The primary outcome measure was a self
      completion Opioid Overdose Knowledge Scale (OOKS; range 0-45) and an Opioid
      Overdose Attitudes Scale (OOAS; range 28-140) was the secondary outcome measure.
      Each group was assessed before receiving their assigned condition and followed-up
      3 months after. Events of witnessing and managing an overdose during follow-up
      were also recorded. FINDINGS: At follow-up, study participants who had received
      THN training reported greater overdose-related knowledge relative to those
      receiving basic information only [OOKS mean difference, 4.08 (95% confidence
      interval, 2.10-6.06; P < 0.001); Cohen's d = 0.74 (0.37-1.10)]. There were also
      more positive opioid overdose-related attitudes among the trained group at follow
      up [OOAS mean difference, 7.47 (3.13-11.82); P = 0.001; d = 0.61 (0.25-0.97)]. At
      the individual level 35 and 54%, respectively, of the experimental group
      increased their knowledge and attitudes compared with 11 and 30% of the control
      group. During follow-up, 13 participants witnessed an overdose with naloxone
      administered on eight occasions: five among the THN-trained group and three among
      the controls. CONCLUSIONS: Take-home naloxone training for family members of
      heroin users increases opioid overdose-related knowledge and competence and these
      benefits are well retained after 3 months.

PMID- 24103088
TI  - Analyses of genetic ancestry enable key insights for molecular ecology.
AB  - Gene flow and recombination in admixed populations produce genomes that are
      mosaic combinations of chromosome segments inherited from different source
      populations, that is, chromosome segments with different genetic ancestries. The
      statistical problem of estimating genetic ancestry from DNA sequence data has
      been widely studied, and analyses of genetic ancestry have facilitated research
      in molecular ecology and ecological genetics. In this review, we describe and
      compare different model-based statistical methods used to infer genetic ancestry.
      We describe the conceptual and mathematical structure of these models and
      highlight some of their key differences and shared features. We then discuss
      recent empirical studies that use estimates of genetic ancestry to analyse
      population histories, the nature and genetic basis of species boundaries, and the
      genetic architecture of traits. These diverse studies demonstrate the breadth of
      applications that rely on genetic ancestry estimates and typify the genomics
      enabled research that is becoming increasingly common in molecular ecology. We
      conclude by identifying key research areas where future studies might further
      advance this field. 

PMID- 24103089
TI  - Glucocorticoid-induced hyperglycemia.
AB  - Corticosteroid-induced hyperglycemia is a common medical problem that can lead to
      frequent emergency room visits, hospital admissions and prolonged hospital stay,
      in addition to the well known morbidity associated with hyperglycemia. However,
      the diagnosis and treatment of corticosteroid-induced hyperglycemia is
      surprisingly undervalued by most professionals, probably because of the lack of
      quality studies to determine specific strategies of action. In the present
      review, we discuss the pathophysiology of corticosteroid-induced hyperglycemia,
      focusing on diverse patterns of hyperglycemia induced by the different
      formulations, and provide clues for diagnosis based on the duration of treatment
      and the administration schedule of corticosteroids. We propose a treatment
      strategy based on both the pathophysiology of the process and the mechanism of
      action of different corticosteroids, and take into account dosing and
      administration timing to predict the duration of therapy. Finally, we propose
      treatment goals that differ slightly between the transient and continuous use of
      corticosteroids based on evidence from clinical practice guidelines of diabetes
      care both in ambulatory and hospital settings. 

PMID- 24103090
TI  - Phenothiazine is a potent inhibitor of prostaglandin E2 production by Candida
      albicans biofilms.
AB  - Candida albicans is an important opportunistic yeast pathogen of humans and has
      the ability to form drug-resistant biofilms, with increased expression of
      multidrug ATP-binding cassette (ABC) transporters. These biofilms are also
      capable of secreting immune-modulating prostaglandin E2 (PGE2 ) from host-derived
      arachidonic acid (AA). Phenothiazine, an aromatic amine, and its derivatives
      display broad activity as inhibitors and antioxidants. These compounds have
      fungistatic and fungicidal activity against planktonic C. albicans and can
      inhibit ABC transporters of C. albicans. This study investigated the effect of
      phenothiazine on biofilm formation, ABC transporters and PGE2 production by C.
      albicans. This was carried out by growing C. albicans biofilms in the presence of
      AA and phenothiazine and measuring the biomass as well as reduction of 2,3-bis(2
      methoxy-4-nitro-5-sulphophenyl)-5[(phenylamino) carbonyl]-2H tetrazolium
      hydroxide. The effect on ABC transporters was determined by rhodamine 6G efflux,
      and the concentration of PGE2 was determined by a monoclonal PGE2 enzyme-linked
      immunosorbent assay and LC/MS/MS. Our results indicate that phenothiazine can
      cause a reduction in both the metabolic activity and biomass of C. albicans
      biofilms, without affecting biofilm morphology or ABC transporters. However, it
      is a potent inhibitor of PGE2 production by C. albicans biofilms.

PMID- 24103091
TI  - Harmful effect of ERbeta on BCRP-mediated drug resistance and cell proliferation
      in ERalpha/PR-negative breast cancer.
AB  - The role of estrogen receptor beta (ERbeta) in breast cancer is still under
      investigation. Various studies have provided evidence that ERbeta behaves as a
      tumor suppressor in breast cancer, whereas some studies of estrogen receptor
      alpha (ERalpha) negative breast cancer reported a positive correlation between
      high ERbeta expression and poor prognostic phenotypes, such as induced
      proliferation, invasion and metastasis. In the present immunohistochemistry study
      of 99 ERalpha/progesterone receptor (PR)-negative breast cancer samples, nuclear
      expression of ERbeta was positively associated with membranous expression of
      breast cancer resistance protein (BCRP), Ki67 (proliferation marker) and tumor
      size. Moreover, both endogenous and exogenous ERbeta upregulated BCRP expression
      which induced BCRP-mediated drug resistance and enhanced proliferation of ERalpha
      /PR- breast cancer cells in the presence of 17beta-estradiol, whereas these
      effects were reversed by additional use of tamoxifen (TAM). In addition, the
      regulation of BCRP via specific binding between ERbeta and estrogen response
      element (ERE) was demonstrated in an electrophoretic mobility shift assay.
      Overall, our findings manifest that ERbeta might act as a tumor promoter of cell
      proliferation and BCRP-mediated drug resistance in ERalpha-/PR- breast cancer.
      TAM routinely used for patients with ERalpha+/PR+, ERalpha+/PR- and ERalpha-/PR+
      breast cancer might also be effective in ERalpha-/PR- but ERbeta+ breast cancer.
      Therefore, the detection of ERbeta in clinic is valuable and should not be
      neglected in breast cancer, especially for the ERalpha-/PR- phenotype. 

PMID- 24103092
TI  - Delay in leaf senescence of Malus hupehensis by long-term melatonin application
      is associated with its regulation of metabolic status and protein degradation.
AB  - Melatonin has an important anti-aging role in plant physiology. We tested the
      effects of long-term melatonin exposure on metabolic status and protein
      degradation during natural leaf senescence in trees of Malus hupehensis Rehd. The
      2-month regular supplement of 100 MUm melatonin to the soil once every 6 days
      altered the metabolic status and delayed protein degradation. For example, leaves
      from treated plants had significantly higher photosynthetic activity, chlorophyll
      concentrations, and levels of three photosynthetic end products (sorbitol,
      sucrose, and starch) when compared with the control. The significant inhibition
      of hexose (fructose and glucose) accumulation possibly regulated the signaling of
      MdHXK1, a gene for which expression was also repressed by melatonin during
      senescence. The plants also exhibited better preservation of their nitrogen,
      total soluble protein, and Rubisco protein concentrations than the control. The
      slower process of protein degradation might be a result of melatonin-linked
      inhibition on the expression of apple autophagy-related genes (ATGs). Our results
      are the first to provide evidence for this delay in senescence based on the
      metabolic alteration and protein degradation. 

PMID- 24103093
TI  - Birds exploit herbivore-induced plant volatiles to locate herbivorous prey.
AB  - Arthropod herbivory induces plant volatiles that can be used by natural enemies
      of the herbivores to find their prey. This has been studied mainly for arthropods
      that prey upon or parasitise herbivorous arthropods but rarely for insectivorous
      birds, one of the main groups of predators of herbivorous insects such as
      lepidopteran larvae. Here, we show that great tits (Parus major) discriminate
      between caterpillar-infested and uninfested trees. Birds were attracted to
      infested trees, even when they could not see the larvae or their feeding damage.
      We furthermore show that infested and uninfested trees differ in volatile
      emissions and visual characteristics. Finally, we show, for the first time, that
      birds smell which tree is infested with their prey based on differences in
      volatile profiles emitted by infested and uninfested trees. Volatiles emitted by
      plants in response to herbivory by lepidopteran larvae thus not only attract
      predatory insects but also vertebrate predators. 

PMID- 24103094
TI  - Restorative proctocolectomy for ulcerative colitis: development and validation of
      a new scoring system for pouch dysfunction and quality of life.
AB  - AIM: The purpose of this study was to develop and validate a pouch dysfunction
      score that could identify the aspects of function which have the greatest impact
      on quality of life as perceived by the patient. METHOD: All (n = 1757) patients
      having restorative proctocolectomy in Denmark between 1980 and 2010 were
      identified. Of these, 1229 were available for study and were sent a questionnaire
      on bowel function and quality of life (QoL) designed specifically for this study.
      Function was correlated with QoL in a multivariate model using ordinal logistic
      regression with QoL as a dependent variable. The pouch dysfunction score was
      developed from a randomly selected half of the study population and the validity
      was tested on the other half. RESULTS: 1047 (85%) patients returned the
      questionnaire. On multivariate analysis, the symptom domains of 'incomplete
      emptying', 'severity of urgency', 'number of bowel movements/24 h', 'major
      incontinence' and 'use of anti-diarrhoeal medication' were associated with
      reduced QoL. The score was divided into three categories including 'none',
      'minor' and 'some/major' pouch dysfunction. The corresponding coefficients gave
      the score a range from 0 to 7.5. There was a highly significant difference (P <
      0.001) in score between the categories. The area under the receiver operating
      curve was 0.81. CONCLUSION: Urgency, incomplete emptying, number of bowel
      movements/24 h, major incontinence and use of anti-diarrhoeal medication have a
      major impact on QoL. There was a high accuracy for the score, demonstrating its
      potential clinical usefulness in relating symptoms to QoL.

PMID- 24103095
TI  - Shrimp pond effluent dominates foliar nitrogen in disturbed mangroves as mapped
      using hyperspectral imagery.
AB  - Conversion of mangroves to shrimp ponds creates fragmentation and eutrophication.
      Detection of the spatial variation of foliar nitrogen is essential for
      understanding the effect of eutrophication on mangroves. We aim (i) to estimate
      nitrogen variability across mangrove landscapes of the Mahakam delta using
      airborne hyperspectral remote sensing (HyMap) and (ii) to investigate links
      between the variation of foliar nitrogen mapped and local environmental
      variables. In this study, multivariate prediction models achieved a higher level
      of accuracy than narrow-band vegetation indices, making multivariate modeling the
      best choice for mapping. The variation of foliar nitrogen concentration in
      mangroves was significantly influenced by the local environment: (1) position of
      mangroves (seaward/landward), (2) distance to the shrimp ponds, and (3)
      predominant mangrove species. The findings suggest that anthropogenic
      disturbances, in this case shrimp ponds, influence nitrogen variation in
      mangroves. Mangroves closer to the shrimp ponds had higher foliar nitrogen
      concentrations.

PMID- 24103096
TI  - Distributions, possible sources and biological risk of DDTs, HCHs and chlordanes
      in sediments of Beibu Gulf and its tributary rivers, China.
AB  - Thirty-five surface sediment samples collected from Beibu Gulf and its tributary
      rivers, China were analyzed for DDTs, HCHs and chlordanes. Total concentrations
      of DDTs, HCHs and chlordanes in sediments ranged from 0.59 to 126 ng g(-)(1), ND
      to 2.65 ng g(-)(1) and 0.27 to 3.41 ng g(-)(1) based on dry weight (dw),
      respectively. Concentrations of DDTs were higher than those reported in the
      sediments from other regions of the world, while concentrations of HCHs and
      chlordanes were relatively low. High concentrations of DDTs were observed in the
      harbor region and aquaculture bases and high concentrations of HCHs were found in
      the Qin River Estuary. The ratios of (DDE+DDD)/DDTs reflected a mixed input of
      weathered and fresh DDTs. The predominant beta-HCH indicated that HCHs in the
      study area mainly originated from the historical usage of technical HCH. The
      residues of DDTs would pose adverse biological effects on the study area.

PMID- 24103097
TI  - Influence of fiber degradation and concentration of fermentable sugars on
      simultaneous saccharification and fermentation of high-solids spruce slurry to
      ethanol.
AB  - BACKGROUND: Saccharification and fermentation of pretreated lignocellulosic
      materials, such as spruce, should be performed at high solids contents in order
      to reduce the cost of the produced bioethanol. However, this has been shown to
      result in reduced ethanol yields or a complete lack of ethanol production.
      Previous studies have shown inconsistent results when prehydrolysis is performed
      at a higher temperature prior to the simultaneous saccharification and
      fermentation (SSF) of steam-pretreated lignocellulosic materials. In some cases,
      a significant increase in overall ethanol yield was reported, while in others, a
      slight decrease in ethanol yield was observed. In order to investigate the
      influence of prehydrolysis on high-solids SSF of steam-pretreated spruce slurry,
      in the present study, the presence of fibers and inhibitors, degree of fiber
      degradation and initial fermentable sugar concentration has been studied.
      RESULTS: SSF of whole steam-pretreated spruce slurry at a solids content of 13.7%
      water-insoluble solids (WIS) resulted in a very low overall ethanol yield, mostly
      due to poor fermentation. The yeast was, however, able to ferment the washed
      slurry and the liquid fraction of the pretreated slurry. Performing prehydrolysis
      at 48 degrees C for 22 hours prior to SSF of the whole pretreated slurry
      increased the overall ethanol yield from 3.9 to 62.1%. The initial concentration
      of fermentable sugars in SSF could not explain the increase in ethanol yield in
      SSF with prehydrolysis. Although the viscosity of the material did not appear to
      decrease significantly during prehydrolysis, the degradation of the fibers prior
      to the addition of the yeast had a positive effect on ethanol yield when using
      whole steam-pretreated spruce slurry. CONCLUSIONS: The results of the present
      study suggest that the increase in ethanol yield from SSF when performing
      prehydrolysis is a result of fiber degradation rather than a decrease in
      viscosity. The increased concentration of fermentable sugars at the beginning of
      the fermentation phase in SSF following prehydrolysis did not affect the overall
      ethanol yield in the present study.

PMID- 24103098
TI  - Using ontologies to study cell transitions.
AB  - BACKGROUND: Understanding, modelling and influencing the transition between
      different states of cells, be it reprogramming of somatic cells to pluripotency
      or trans-differentiation between cells, is a hot topic in current biomedical and
      cell-biological research. Nevertheless, the large body of published knowledge in
      this area is underused, as most results are only represented in natural language,
      impeding their finding, comparison, aggregation, and usage. Scientific
      understanding of the complex molecular mechanisms underlying cell transitions
      could be improved by making essential pieces of knowledge available in a formal
      (and thus computable) manner. RESULTS: We describe the outline of two ontologies
      for cell phenotypes and for cellular mechanisms which together enable the
      representation of data curated from the literature or obtained by bioinformatics
      analyses and thus for building a knowledge base on mechanisms involved in
      cellular reprogramming. In particular, we discuss how comprehensive ontologies of
      cell phenotypes and of changes in mechanisms can be designed using the entity
      quality (EQ) model. CONCLUSIONS: We show that the principles for building
      cellular ontologies published in this work allow deeper insights into the
      relations between the continuants (cell phenotypes) and the occurrents (cell
      mechanism changes) involved in cellular reprogramming, although implementation
      remains for future work. Further, our design principles lead to ontologies that
      allow the meaningful application of similarity searches in the spaces of cell
      phenotypes and of mechanisms, and, especially, of changes of mechanisms during
      cellular transitions.

PMID- 24103099
TI  - Ageing and apoE change DHA homeostasis: relevance to age-related cognitive
      decline.
AB  - Epidemiological studies fairly convincingly suggest that higher intakes of fatty
      fish and n-3 fatty acids are associated with reduced risk of Alzheimer's disease
      (AD). DHA in plasma is normally positively associated with DHA intake. However,
      despite being associated with lower fish and DHA intake, unexpectedly, plasma (or
      brain) DHA is frequently not lower in AD. This review will highlight some
      metabolic and physiological factors such as ageing and apoE polymorphism that
      influence DHA homeostasis. Compared with young adults, blood DHA is often
      slightly but significantly higher in older adults without any age-related
      cognitive decline. Higher plasma DHA in older adults could be a sign that their
      fish or DHA intake is higher. However, our supplementation and carbon-13 tracer
      studies also show that DHA metabolism, e.g. transit through the plasma, apparent
      retroconversion and beta-oxidation, is altered in healthy older compared with
      healthy young adults. ApoE4 increases the risk of AD, possibly in part because it
      too changes DHA homeostasis. Therefore, independent of differences in fish
      intake, changing DHA homeostasis may tend to obscure the relationship between DHA
      intake and plasma DHA which, in turn, may contribute to making older adults more
      susceptible to cognitive decline despite older adults having similar or sometimes
      higher plasma DHA than in younger adults. In conclusion, recent development of
      new tools such as isotopically labelled DHA to study DHA metabolism in human
      subjects highlights some promising avenues to evaluate how and why DHA metabolism
      changes during ageing and AD. 

PMID- 24103100
TI  - The microwave-assisted ionic liquid nanocomposite synthesis: platinum
      nanoparticles on graphene and the application on hydrogenation of styrene.
AB  - The microwave-assisted nanocomposite synthesis of metal nanoparticles on graphene
      or graphite oxide was introduced in this research. With microwave assistance, the
      Pt nanoparticles on graphene/graphite oxide were successfully produced in the
      ionic liquid of 2-hydroxyethanaminium formate [HOCH2CH2NH3][HCO2]. On
      graphene/graphite oxide, the sizes of Pt nanoparticles were about 5 to 30 nm from
      transmitted electron microscopy (TEM) results. The crystalline Pt structures were
      examined by X-ray diffraction (XRD). Since hydrogenation of styrene is one of the
      important well-known chemical reactions, herein, we demonstrated then the
      catalytic hydrogenation capability of the Pt nanoparticles on graphene/graphite
      oxide for the nanocomposite to compare with that of the commercial catalysts
      (Pt/C and Pd/C, 10 wt.% metal catalysts on activated carbon from Strem chemicals,
      Inc.). The conversions with the Pt nanoparticles on graphene are >99% from
      styrene to ethyl benzene at 100 degrees C and under 140 psi H2 atmosphere.
      However, ethyl cyclohexane could be found as a side product at 100 degrees C and
      under 1,520 psi H2 atmosphere utilizing the same nanocomposite catalyst. 

PMID- 24103101
TI  - Hepatitis E virus infection as a new probable cause of de novo membranous
      nephropathy after kidney transplantation.
AB  - Hepatitis E virus (HEV) has been identified as a cause of chronic viral hepatitis
      in immunocompromised patients. Some glomerular diseases were found to be
      associated with this infection. We report the first case, to our knowledge, of a
      kidney transplant recipient who developed an HEV infection and de novo membranous
      nephropathy (MN) concomitantly. The patient displayed a hepatic cytolysis first
      and a nephrotic syndrome occurred 3 months later. HEV infection was diagnosed
      upon positive polymerase chain reaction on plasma and stool samples, and renal
      allograft biopsy revealed de novo MN. Typical causes of MN were definitively
      excluded. A 3-month course of ribavirin monotherapy allowed the patient to mount
      a sustained viral response that was rapidly followed by complete remission of the
      nephrotic syndrome. The chronology of the onset and remission of both diseases is
      highly suggestive of a causal relationship between hepatitis E and MN.

PMID- 24103102
TI  - Impaired coronary flow reserve in patients with indeterminate form of Chagas'
      disease.
AB  - BACKGROUND: Previous studies suggest that microvascular abnormalities may
      contribute to the pathogenesis of Chagas' heart disease. Coronary flow reserve
      (CFR) expressed by the maximum achievable flow relative to baseline flow in the
      coronary microcirculation, may be useful in identifying patients who may be
      developing cardiac manifestations of the disease. This study aims to assess the
      CFR in patients with indeterminate form of Chagas' disease, and also to identify
      the determinants of CFR. METHODS: Sixty-four asymptomatic patients (37% male; age
      49.9 +/- 11.5 years) with normal cardiovascular exams classified as in
      indeterminate form of Chagas' disease underwent transthoracic dipyridamole (0.84
      mg/kg in 6 min) stress echocardiography, and were compared with a control group
      of healthy patients. Coronary flow reserve was assessed on left anterior
      descending artery using pulsed Doppler as the ratio of maximal peak vasodilation
      (dipyridamole) to rest diastolic flow velocity. A treadmill exercise test was
      performed to rule out ischemia. RESULTS: All patients had good functional
      capacity assessed by exercise testing with peak oxygen consumption (VO2 ) of 28
      +/- 11 mL/kg per minute, similar to the controls. There were no differences in
      the echocardiographic parameters of diastolic and systolic left ventricular
      function and right ventricular function between the patients and controls.
      Coronary flow reserve was significantly lower in Chagas' disease patients than
      those in healthy individuals (1.9 +/- 0.4 vs. 2.6 +/- 0.5; P < 0.001). Several
      factors were correlated with the CFR, including age, ejection fraction, left
      ventricular diastolic function, heart rate recovery, and the presence of Chagas'
      disease. In a multivariate analysis, age and positive serology for Chagas'
      disease were independent factors associated with the CFR. CONCLUSIONS: Coronary
      flow reserve was impaired in Chagas' disease patients in the indeterminate form
      compared with healthy individuals with similar clinical features. Among all
      variables tested, age and positive serology for Chagas' disease were independent
      factors associated with the CFR.

PMID- 24103103
TI  - Genetic characterization of CCL3, CCL4 and CCL5 in leporid genera Oryctolagus,
      Sylvilagus and Lepus.
AB  - The genetic diversity of C-C motif chemokine receptor 5 (CCR5) ligands CCL3, CCL4
      and CCL5 in the leporid genera Oryctolagus, Sylvilagus and Lepus was studied. Our
      results demonstrate that the three CCR5 chemokine ligands are under strong
      purifying selection as a result of possible functional binding constraints. 

PMID- 24103104
TI  - The role of adult attachment and social support in hoarding disorder.
AB  - BACKGROUND: Research concerning the role of attachment and social support in
      hoarding is currently under investigated. AIMS: To investigate whether hoarders
      experience less social support and more problematic relationships, the degree to
      which attachment and social support predicts hoarding and whether attachment
      moderates the relationship between social support and hoarding. METHOD: Measures
      of hoarding, attachment and social support were taken in a cross-sectional
      methodological design. Hoarders were identified via scores reaching caseness on
      the Savings Inventory-Revised (SI-R). RESULTS: Hoarders (N = 380) reported
      significantly higher levels of attachment anxiety and avoidance and significantly
      lower levels of social support than student (N = 670) and community (N = 379)
      controls. Attachment and social support predicted 13% of total SI-R scores for
      hoarders, and attachment anxiety (but not avoidance) moderated the inverse
      relationship between social support and hoarding. CONCLUSIONS: Attachment and
      social support appears problematic for hoarders. Clinical implications and
      methodological issues are noted.

PMID- 24103106
TI  - Separating viscoelastic and compressibility contributions in pressure-area
      isotherm measurements.
AB  - Monolayers of surface active molecules or particles play an important role in
      biological systems as well as in consumer products. Their properties are
      controlled by thermodynamics as well as the mechanical properties of the
      interface itself. For insoluble species forming Langmuir monolayers, surface
      pressure-area isotherms are typically used to characterize the thermodynamic
      state. A Langmuir trough equipped with a Wilhelmy plate is often used for such
      measurements. However, when Langmuir interfaces are compressed and become more
      structured, the elastic response of these interfaces can interfere with the
      measurement of the surface pressure-area isotherm, even when the compression
      speed is slow. Recent reports of compression data for highly elastic interfaces
      revealed a dependence of the apparent surface pressures on the geometry of the
      measurement trough. In the present work, this dependence is investigated by
      considering adequate constitutive models. Since deformations in such compression
      experiments can be large, linearized versions of the Kelvin-Voigt model do not
      suffice. We develop a framework for quasi-linear constitutive models by choosing
      suitable non-linear strain tensors, adequately separating the shear and
      dilatational effects in a frame invariant manner. The proposed constitutive
      models can be used as building blocks to describe viscoelastic behavior as well.
      The geometry dependence in isotherm measurements is then shown to be a
      consequence of varying contributions of the isotropic surface pressure and extra
      shear and dilatational elastic stresses. Using these insights, an approach is
      proposed to obtain the intrinsic surface pressure-area isotherms for elastic
      interfaces. As a case study, experimental data on graphene oxidesheets at the air
      water interface is investigated to evaluate the proposed model. 

PMID- 24103105
TI  - Evolutionary interactions between haemagglutinin and neuraminidase in avian
      influenza.
AB  - BACKGROUND: Reassortment between the RNA segments encoding haemagglutinin (HA)
      and neuraminidase (NA), the major antigenic influenza proteins, produces viruses
      with novel HA and NA subtype combinations and has preceded the emergence of
      pandemic strains. It has been suggested that productive viral infection requires
      a balance in the level of functional activity of HA and NA, arising from their
      closely interacting roles in the viral life cycle, and that this functional
      balance could be mediated by genetic changes in the HA and NA. Here, we
      investigate how the selective pressure varies for H7 avian influenza HA on
      different NA subtype backgrounds. RESULTS: By extending Bayesian stochastic
      mutational mapping methods to calculate the ratio of the rate of non-synonymous
      change to the rate of synonymous change (d(N)/d(S)), we found the average
      d(N)/d(S) across the avian influenza H7 HA1 region to be significantly greater on
      an N2 NA subtype background than on an N1, N3 or N7 background. Observed
      differences in evolutionary rates of H7 HA on different NA subtype backgrounds
      could not be attributed to underlying differences between avian host species or
      virus pathogenicity. Examination of d(N)/d(S) values for each subtype on a site
      by-site basis indicated that the elevated d(N)/d(S) on the N2 NA background was a
      result of increased selection, rather than a relaxation of selective constraint.
      CONCLUSIONS: Our results are consistent with the hypothesis that reassortment
      exposes influenza HA to significant changes in selective pressure through genetic
      interactions with NA. Such epistatic effects might be explicitly accounted for in
      future models of influenza evolution.

PMID- 24103107
TI  - Course of weight gain and metabolic abnormalities in first treated episode of
      psychosis: the first year is a critical period for development of cardiovascular
      risk factors.
AB  - Data on the long-term metabolic side-effects associated with antipsychotics are
      scarce. Prospective longitudinal studies in medication-naive patients with a
      first episode of psychosis are a valuable source of information as they provide
      an assessment prior to the antipsychotic exposure and minimize the effect of
      potential confounding factors. The aim of this study was to assess the course of
      weight gain and the incidence of metabolic abnormalities during the first 3 yr of
      antipsychotic treatment. Data were collected from a cohort of 170 first-episode
      psychosis patients. They were randomly assigned to haloperidol (32%); olanzapine
      (32%) and risperidone (36%). The dose used was flexible. The initial
      antipsychotic treatment was changed when required, based on clinical response and
      tolerability. The results showed that the mean weight gain at 3 yr was 12.1 kg
      (s.d. = 10.7). It appeared to increase rapidly during the first year (85% of the
      total mean weight gain) and then stabilized gradually over time. Total
      cholesterol, LDL-cholesterol and triglyceride levels followed a similar
      trajectory with a significant increase only during the first year. No significant
      changes were detected in the mean values of glycaemic parameters. Two patients
      with a family history of diabetes developed diabetes type II. At short-term the
      factors positively associated with weight gain were lower body mass index, male
      gender and olanzapine treatment. At long-term, functional status and clinical
      response were the main predictors. The results of our study indicate that the
      first year of antipsychotic treatment is a critical period for weight gain and
      metabolic changes. Identification of weight gain patterns may help to inform
      studies that aim to prevent or mitigate the metabolic adverse events associated
      with antipsychotic therapy. 

PMID- 24103108
TI  - Educational outreach visits to improve venous thromboembolism prevention in
      hospitalised medical patients: a prospective before-and-after intervention study.
AB  - BACKGROUND: Despite the availability of evidence-based guidelines on venous
      thromboembolism (VTE) prevention clinical audit and research reveals that
      hospitalised medical patients frequently receive suboptimal prophylaxis. The aim
      of this study was to evaluate the acceptability, utility and clinical impact of
      an educational outreach visit (EOV) on the provision of VTE prophylaxis to
      hospitalised medical patients in a 270 bed acute care private hospital in
      metropolitan Australia. METHODS: The study used an uncontrolled before-and-after
      design with accompanying process evaluation. The acceptability of the
      intervention to participants was measured with a post intervention survey;
      descriptive data on resource use was collected as a measure of utility; and
      clinical impact (prophylaxis rate) was assessed by pre and post intervention
      clinical audits. Doctors who admit >40 medical patients each year were targeted
      to receive the intervention which consisted of a one-to-one educational visit on
      VTE prevention from a trained peer facilitator. The EOV protocol was designed by
      a multidisciplinary group of healthcare professionals using social marketing
      theory. RESULTS: Nineteen (73%) of 26 eligible participants received an EOV. The
      majority (n = 16, 85%) felt the EOV was effective or extremely effective at
      increasing their knowledge about VTE prophylaxis and 15 (78%) gave a verbal
      commitment to provide evidence-based prophylaxis. The average length of each
      visit was 15 minutes (IQ range 15 to 20) and the average time spent arranging and
      conducting each visit was 92 minutes (IQ range 78 to 129). There was a
      significant improvement in the proportion of medical patients receiving
      appropriate pharmacological VTE prophylaxis following the intervention (54% to
      70%, 16% improvement, 95% CI 5 to 26, p = 0.004). CONCLUSIONS: EOV is effective
      at improving doctors' provision of pharmacological VTE prophylaxis to
      hospitalised medical patients. It was also found to be an acceptable
      implementation strategy by the majority of participants; however, it was resource
      intensive requiring on average 92 minutes per visit.

PMID- 24103109
TI  - Non-specific sex-differential effect of DTP vaccination may partially explain the
      excess girl child mortality in Ballabgarh, India.
AB  - OBJECTIVE: To test the hypothesis that a gender differential exists in the effect
      on child mortality of BCG, DTP, measles vaccine as administered under programme
      conditions in Ballabgarh HDSS area. METHODS: All live births in 28 villages of
      Ballabgarh block in North India from 2006 to 2011 were followed until 31 December
      2011 or 36 months of age whichever was earlier. The period of analysis was
      divided into four time periods based on eligibility for vaccines under the
      national immunisation schedule (BCG for tuberculosis, primary and booster doses
      of diphtheria-tetanus-pertussis and measles). Cox proportional hazards regression
      was used to assess the association between sex and risk of mortality by
      vaccination status using age as the timescale in survival analysis and adjusting
      for wealth index, access to health care, the presence of a health facility in the
      village, parental education, type of family, birth order of the child and year of
      birth. RESULTS: 702 deaths (332 boys and 370 girls) occurred among 12,142
      children in the cohort in the 3 years of follow-up giving a cumulative mortality
      rate of 57.5 per 1000 live births with 35% excess girl child mortality. Age at
      vaccination for the four vaccines did not differ by sex. There was significant
      excess mortality among girls after immunisation with DTP, for both primary (HR
      1.65; 95% CI:1.17-2.32) and DTPb (2.21; 1.24-3.93) vaccinations. No significant
      excess morality among girls was noted after exposure to BCG 1.06 (0.67-1.67) or
      measles 1.34 (0.85-2.12) vaccine. CONCLUSION: This study supports the contention
      that DTP vaccination is partially responsible for higher mortality among girls in
      this study population.

PMID- 24103110
TI  - Live imaging of symbiosis: spatiotemporal infection dynamics of a GFP-labelled
      Burkholderia symbiont in the bean bug Riptortus pedestris.
AB  - Many insects possess endosymbiotic bacteria inside their body, wherein intimate
      interactions occur between the partners. While recent technological advancements
      have deepened our understanding of metabolic and evolutionary features of the
      symbiont genomes, molecular mechanisms underpinning the intimate interactions
      remain difficult to approach because the insect symbionts are generally
      uncultivable. The bean bug Riptortus pedestris is associated with the
      betaproteobacterial Burkholderia symbiont in a posterior region of the midgut,
      which develops numerous crypts harbouring the symbiont extracellularly. Distinct
      from other insect symbiotic systems, R. pedestris acquires the Burkholderia
      symbiont not by vertical transmission but from the environment every generation.
      By making use of the cultivability and the genetic tractability of the symbiont,
      we constructed a transgenic Burkholderia strain labelled with green fluorescent
      protein (GFP), which enabled detailed observation of spatiotemporal dynamics and
      the colonization process of the symbiont in freshly prepared specimens. The
      symbiont live imaging revealed that, at the second instar, colonization of the
      symbiotic midgut M4 region started around 6 h after inoculation (hai). By 24 hai,
      the symbiont cells appeared in the main tract and also in several crypts of the
      M4. By 48 hai, most of the crypts were colonized by the symbiont cells. By 72
      hai, all the crypts were filled up with the symbiont cells and the symbiont
      localization pattern continued during the subsequent nymphal development.
      Quantitative PCR of the symbiont confirmed the infection dynamics quantitatively.
      These results highlight the stinkbug-Burkholderia gut symbiosis as an
      unprecedented model for comprehensive understanding of molecular mechanisms
      underpinning insect symbiosis.

PMID- 24103111
TI  - Monocytic myeloid-derived suppressor cells accumulate in renal transplant
      patients and mediate CD4(+) Foxp3(+) Treg expansion.
AB  - Myeloid-derived suppressor cells (MDSC) are negative regulators of the immune
      response and are in part responsible for the inhibition of the T cell-mediated
      immune responses. While MDSC have been demonstrated to participate in the
      induction of prolonged allograft survival in animal models of transplantation,
      little is known about their immune regulatory function in human transplant
      recipients. Here, we report that two subsets of human MDSC expressing CD11b(+),
      CD33(+) and HLA-DR(-) develop in renal patients posttransplantation. We found
      that CD14(+) expressing monocytic MDSC isolated from transplant recipients were
      highly efficient in suppressing the proliferation of CD4(+) T cells in mixed
      leukocyte reactions. In addition, we observed that CD11b(+) CD33(+) HLA-DR(-)
      MDSC are capable of expanding Treg in vitro, and their accumulation overtime
      after transplantation linearly correlated with an increase in Treg in vivo. This
      is the first study to link the presence of MDSC with the emergence of Treg in
      vivo in transplant recipients, and to define the subpopulation of MDSC derived
      from transplant recipients responsible for generation of Treg. Further studies
      are necessary to determine the alloimmune regulatory function of MDSC in human
      transplant recipients.

PMID- 24103112
TI  - Fever in children--a concept analysis.
AB  - AIMS AND OBJECTIVES: To undertake a concept analysis to clarify the meaning of
      the term 'fever' in children and to identify models of fever-related belief that
      may help in understanding the response of parents and professionals to fever in
      children. BACKGROUND: This concept analysis was undertaken because the approach
      to the treatment of fever varies widely and in particular that there is often a
      difference between what parents want for their children, official guidelines and
      what professionals do in practice. DESIGN: Concept analysis. METHODS: The study
      used a modified evolutionary method of concept analysis. The analysis was based
      on data from medical, nursing, popular and biological literature and used an
      iterative process to clarify the term. RESULTS: Fever has a number of distinct
      uses based on its meaning and history; these include its use to indicate an
      illness itself, as a beneficial symptom associated with disease, and a diagnostic
      sign. Three models of fever-related practice emerged from the analysis, these
      being a phobic-fearful approach that drives routine treatment, a scientific
      approach that sees fever as a potentially adaptive and beneficial response and a
      scientific but pragmatic approach that recognises potential benefit but results
      in treatment anyway. These different uses, which are often not clarified, go some
      way to explaining the different approaches to its treatment. CONCLUSIONS: When
      parents, clinicians, physiologists and guideline writers discuss fever, they
      attribute different meanings to it, which may go some way to explaining the
      dissonance between theory and practice. In the absence of new knowledge, the
      emphasis of practitioners should therefore be on their safe use. RELEVANCE TO
      PRACTICE: When discussing the meaning and treatment of fever, it is important to
      understand what is meant in different circumstances. The models of fever-related
      beliefs outlined here may go some way to helping this process.

PMID- 24103113
TI  - Long-term evaluation of ANKYLOS(r) dental implants, part i: 20-year life table
      analysis of a longitudinal study of more than 12,500 implants.
AB  - PURPOSE: Scientific evidence is limited regarding the long-term (>10 years)
      outcomes of large enough numbers of implants (>500) to allow for reliable
      comparison of subgroups. The purpose of this study was to analyze the outcomes of
      dental implants placed in an active University Clinic setting and followed for up
      to 20 years. MATERIALS AND METHODS: Data documenting the implant placement,
      prosthetic reconstruction, and annual follow-up of patients treated at Frankfurt
      University were extracted from a Structured Query Language database and patients'
      written records and evaluated statistically. RESULTS: Between April of 1991 and
      May of 2011, 12,737 ANKYLOS(r) (DENTSPLY Implants Manufacturing GmbH, Mannheim,
      Germany) implants were placed in 4,206 patients for a variety of clinical
      indications. The Kaplan-Meier cumulative survival rate (CSR) was 93.3% after 204
      months. Most of the failures (198/1.6%) occurred during the first year after
      implant placement and before prosthesis delivery. A significantly higher (p <
      .001) number of implants placed in the mandible and in hard quality bone failed
      than those placed in the maxilla or in weak and normal quality bone. Female
      patients had significantly higher CSRs (93.7% 204 months) than male patients
      (92.8% 204 months/p = .029). The implants showed low rates of peri-implant bone
      loss after 204 months (horizontal: <=1 mm: 85.7%, vertical: <=1 mm: 85.2%).
      CONCLUSION: ANKYLOS dental implants followed for up to 20 years have high CSRs
      and low rates of peri-implant bone loss.

PMID- 24103114
TI  - Radiologic assessment of retropharyngeal node involvement in oropharyngeal
      carcinomas stratified by HPV status.
AB  - Radiation of retropharyngeal nodes (RPN) results in increased toxicities. This
      study assessed characteristics associated with RPN involvement in 165 oropharynx
      cancer patients. Factors associated with involvement were stage N2c-3 disease and
      stage N2b disease with either advanced T-stage, ?3 involved cervical LN, and ?1
      involved contralateral LN, or lateral/posterior subsites. 

PMID- 24103116
TI  - [Attention to clinical study of monochorionic twin pregnancies].

PMID- 24103115
TI  - Incidence of intussusception in Singaporean children aged less than 2 years: a
      hospital-based prospective study.
AB  - BACKGROUND: Continuous surveillance for intussusception (IS) is important for
      monitoring the safety of second-generation rotavirus vaccines. The present study
      aimed to assess the incidence of IS in Singaporean children aged < 2 years.
      METHODS: This was a prospective, hospital-based, multi-center surveillance
      conducted in seven hospitals - two public hospitals and five private medical
      centers between May 2002 and June 2010 in Singapore. Diagnosis of IS (definite,
      probable, possible, suspected) was based on the case definition developed by the
      Brighton Collaboration. Children < 2 years of age who were diagnosed with IS were
      enrolled in this study. Incidence of IS was calculated per 100,000 child-year
      with its 95% confidence interval. RESULTS: Of the 178 children enrolled, 167
      children with definite IS cases were considered for final analyses; 11 were
      excluded (six diagnosed as probable IS and four diagnosed as suspected IS; one
      child's parents withdrew consent). Mean age of children with definite IS was 11.6
      +/- 6 months; 67.7% were males. The overall incidence of IS was 28.9 (95% CI:
      23.0-34.8) and 26.1 (95% CI: 22.2-30.0) per 100,000 child-year in children < 1
      year and < 2 years of age, respectively. The majority of IS cases (20 [12.0%])
      were reported in children aged 6 months. Most children (98.2% [164/167])
      recovered, two (1.2%) children recovered with sequelae and one (0.6%) child died
      of septic shock. CONCLUSIONS: The incidence of IS remained low and stable in
      Singaporean children aged < 2 years during the study period (May 2002 to June
      2010). TRIAL REGISTRATION: NCT01177839.

PMID- 24103117
TI  - [Perinatal outcome of monochorionic twin pregnancies].
AB  - OBJECTIVE: To study the perinatal outcome of monochorionic (MC) twin pregnancies.
      METHODS: The 197 cases of MC twin pregnancies delivered in obstetric unit of
      Prince of Wales Hospital from Jan. 2005 to Dec. 2010 were enrolled in this
      retrospective study,which were divided into 3 groups:uncomplicated MC pregnancy
      (136 cases), twin to twin transfusion syndrome (TTTS, 32 cases), selective
      intrauterine growth restriction (sIUGR, 29 cases). RESULTS: (1) The gestational
      age at delivery in TTTS (30 weeks vs.37 weeks, P<0.01) or sIUGR (34 weeks vs.37
      weeks, P<0.01) group were significantly lower than those in uncomplicated MC
      pregnancy. The number of live-born in TTTS (36 cases) or sIUGR (47 cases) group
      were significantly lower than those in uncomplicated MC pregnancy (261 cases,
      P<0.01). (2) The incidence of fetal death (IUFD) in TTTS [34% (11/32) vs. 4%
      (6/136), P<0.01] or sIUGR group [28% (8/29) vs. 4% (6/136), P<0.01] were
      significantly higher than those in uncomplicated MC pregnancy group. (3) The
      incidence of birth weight (BW) discordance>25% in TTTS [5/15 vs.7.7% (10/130),
      P<0.05] or sIUGR [33% (7/21) vs. 7.7% (10/130), P<0.05] group were significantly
      higher than those in uncomplicated MC pregnancy group. (4) The incidence of
      preterm delivery before 37 weeks was 49% (66/136) and 69% (20/29) respectively in
      uncomplicated MC pregnancy and sIUGR. The incidence of preterm delivery in sIUGR
      group were significantly higher than that in uncomplicated MC pregnancy group
      (P<0.05). (5) The incidence of perinatal mortality in TTTS[12%(5/41) vs.0.4%
      (1/262), P<0.01] or sIUGR [10%(5/52) vs. 0.4% (1/262), P<0.01] group were
      significantly higher than those in uncomplicated MC pregnancy group. (6) The
      incidence of estimated fetal weight (EFW) discordance>25% was 17% (23/136) in
      uncomplicated MC pregnancy, 52% (15/29) in sIUGR, 63% (20/32) in TTTS. In
      uncomplicated MC pregnancy or sIUGR, pregnancies with EFW discordance>25% was
      associated with lower gestational age at delivery, higher incidence of preterm
      delivery and admission to NICU than those with EFW discordance<=25% (P<0.05). In
      uncomplicated MC pregnancy, pregnancies with EFW discordance>25% was associated
      with higher incidence of neonatal asphyxia (Apgar score 1 minute<=7) than those
      with EFW discordance<=25% (P<0.05). (7) Compared to uncomplicated MC pregnancy,
      the incidence of umbilical artery (UmA) flow abnormality was higher in TTTS[38%
      (12/32) vs. 9.6% (13/136), P<0.01] or sIUGR [41% (12/29) vs. 9.6% (13/136),
      P<0.01]. The incidence of IUFD in pregnacies with UmA flow abnormality was 2/13,
      6/12 and 5/12 respectively in uncomplicated MC pregnancy, TTTS and sIUGR.
      CONCLUSIONS: MC pregnancies complicated by either TTTS or sIUGR have poorer
      perinatal outcome as compared with uncomplicated MC pregnancies. MC pregnancies
      with EFW discordance>25% and UmA flow abnormality are associated with even worse
      perinatal outcome. Close fetal monitoring is needed in MC pregnancies in order to
      reduce perinatal mortality.

PMID- 24103118
TI  - [Research of placental vascular distribution and clinical outcome in
      monochorionic twins].
AB  - OBJECTIVE: To study the placental vascular distribution of monochorionic (MC)
      twins with twin-to-twin transfusion syndrome (TTTS) or birth weight discordance.
      METHODS: Twenty-eight MC placentas were injected in Peking University Third
      Hospital between Feb. 2010 and Feb. 2011. The vascular distribution type
      (parallel, crossed, mixed and monoamniotic), the anastomosis of vessels and the
      placental sharing were recorded. The outcome of pregnancy and the placental
      characteristics of birth weight discordance (birth weight discordance>=20%) in
      non-TTTS MC twins were analyzed. RESULTS: (1) The outcome of pregnancy: the
      miscarriage or gestational weeks of 28 MC twins were 20 to 38 weeks (median of 35
      weeks). Six cases were TTTS, 3 of which received fetoscopic laser occlusion of
      communicating vessels (FLOC). There were 48 live births, with an average birth
      weight of (2036+/-623) g. (2) Type of placental vascular distribution:in the 28
      MC placentas, number of parallel, crossed, mixed and monoamniotic type of
      placental vascular distribution were 4 (14%), 14 (50%), 6 (21%) and 4 (14%)
      cases, respectively. No parallel type was found in TTTS. There was no significant
      difference of vascular anastomosis or unequal placental sharing among the
      different placental vascular distribution types (P>0.05). (3) Characteristics of
      placental vascular distribution in birth weight discordance twins:there were 20
      non-TTTS MC twin pregnancies, all of which got live births of both babies. Birth
      weight discordance equal to or more than 20% was found in 6 pairs of newborns,
      while birth weight discordance less than 20% was found in the rest 14 cases.
      Ratio of unequal placental sharing was significantly different between the two
      groups (P<0.01). There was no significant difference of umbilical cord insertion,
      placental vascular distribution and anastomosis in the two groups (P>0.01).
      CONCLUSIONS: Vascular distribution type of MC twins might be related to TTTS.
      Unequal placental sharing is a risk factor of birth weight discordance in non
      TTTS MC twins.

PMID- 24103119
TI  - [Perinatal outcome of monochorionic diamniotic twins with selective intrauterine
      growth restriction].
AB  - OBJECTIVE: To evaluate the perinatal outcome of three types of monochorionic
      diamniotic (MCDA) twins with selective intrauterine growth restriction (sIUGR).
      METHODS: From January 2005 to June 2012, clinical data of 42 pairs of MCDA twins
      (84 fetuses) with sIUGR and 71 pairs of normal MCDA twins (142 fetuses) in the
      same period were analyzed retrospectively in the First Affiliated Hospital of Sun
      Yat-Sen University. Fetuses with sIUGR were classified into three groups based on
      umbilical artery Doppler flow.There were 25 cases of type I, 11 cases of type II
      and 6 cases of type III. The perinatal outcome was compared between sIUGR and
      normal MCDA twins, and among the three types of sIUGR as well. Perinatal outcomes
      included gestational age at delivery, rate of intrauterine fetal death (IUFD),
      birth weight, intertwin discordance of birth weight, neonatal death and survival
      rate at 6 months. RESULTS: (1) The gestational age of sIUGR at delivery was
      significantly earlier than the control group [(34+/-3), (36+/-2) weeks,
      respectively], and the rate of IUFD of both fetuses of sIUGR was significantly
      higher (4.8%, 0, respectively). In the sIUGR group, the average birth weight of
      large or small twins [(2130+/-350), (1520+/-400) g, respectively] was smaller
      than those in the control group [(2470+/-500), (2340+/-460) g, respectively]. The
      difference was statistically significant (P<0.05, P<0.01, respectively). The
      intertwin discordance of birth weight in sIUGR group was significantly larger
      (27.6%) than the control group (4.0%, P<0.01). (2) The gestational age at
      delivery in type II and type III [(34+/-5), (34+/-2) weeks, respectively] was
      significantly earlier than the control group (P<0.05). The rate of IUFD of both
      fetuses in type II (18%) was significantly higher than in type I (0) and the
      control group (0, P<0.05). In sIUGR group, the average birth weight of small
      twins in type I, type II and type III was (1640+/-430), (1330+/-310) and (1500+/
      380) g respectively, all of which were significantly smaller than that in the
      control group (P<0.05). The average birth weight of small twins in type II was
      smaller than in type I and the difference was statistically significant (P<0.05).
      In sIUGR group, the intertwin discordance of birth weight in type I, type II and
      type III was 24.1%, 34.6%, 31.3% respectively, all of which were significantly
      larger than that in the control group (4.0%, P<0.05). There were no statistically
      significant differences of the intertwin discordance of birth weight among the
      three types of sIUGR (P>0.05). Survival rate at 6 months in type II (64%) was
      significantly lower than in type I (92%) and the control group (91.5%, P<0.01).
      CONCLUSIONS: The perinatal outcome of MCDA twins with sIUGR is poor. The outcome
      is different among the three types of sIUGR, and typeIIis the worst. Type II is
      associated with a high risk of intrauterine fetal demise. It is important to
      monitor the intrauterine situation closely.

PMID- 24103120
TI  - [Expression and function of chemokine TARC/CCR4 at fetal-maternal interface in
      first trimester].
AB  - OBJECTIVE: To investigate the expression and function of thymus and activation
      regulated chemokine (TARC) and its special receptor CCR4 at placenta villous in
      the first trimester placenta villous. METHODS: Placenta villous was collected
      from healthy women undergoing artificial abortion at 6 to 8 weeks of gestation.
      mRNA levels of TARC, CCR4 were analyzed using semi-quantitative reverse
      transcription (RT)-PCR methods. Immunohistochemistry assay was used to assess the
      protein localization and expression of TARC, CCR4. Additionally, extravillous
      cytotrophoblasts were isolated and cultured. Expression of TARC and CCR4 was
      measured by immunofluorescence assay. Invasion of cell line HTR8/SVneo was
      analyzed by transwell assay at concentration of 10, 25, 50 and 100 ng/ml of TARC
      matched with RPMI 1640 fetal bovine serum free culture medium as control group.
      In the mean time, blocking experiment was also added to detect TARC regulating
      cell invasion, which were classified into four groups: control, 100 ng/ml rhTARC,
      20 ug/ml anti-TARC+100 ng/ml rhTARC, 100 ng/ml rhTARC+20 ug/ml IgG. The influence
      of 100 ng/ml TARC on expression level of integrin-alpha5 and integrin-beta1 were
      measured by using western-blot assay. RESULTS: (1) In vivo assay:expression of
      TARC and CCR4 mRNA were detectable in first trimester placenta villous, TARC
      protein was localized in cytotrophoblasts, syncytiotrophoblasts and cell column
      especially on the distal portion, while CCR4 protein was localized on invading
      interstitial cytotrophobalsts. (2) In vitro assay: a. TARC, CCR4 was also
      expressed in primary isolated extravillous cytotrophoblasts by immunofluorescence
      assay; b. Matrigel invasion assay demonstrated that TARC had specific dose
      dependent stimulatory effects on the cells invading through the matrigel
      precoated filter, the number of cells migration into the lower chamber were:142+/
      31 at 10 ng/ml group, 161+/-46 at 25 ng/ml group, 201+/-30 at 50 ng/ml group,
      312+/-48 at 100 ng/ml group, 117+/-33 at control group, the significant response
      observed from 25 ng/ml (P<0.05) and reached a peak effect at 100 ng/ml (P<0.01);
      c. Blocking experiment demonstrated that when trophoblast invasion was monitored
      in response to TARC neutralizing antibody (15 ug/ml) together with rhTARC 100
      ng/ml. The stimulatory activity of rhTARC was completely overcome, with the cells
      invasion into the lower chambers were 100 ng/ml rhTARC, 20 ug/ml anti-TARC+100
      ng/ml rhTARC, 100 ng/ml rhTARC+20 ug/ml IgG, control: 313+/-47, 113+/-41, 287+/
      75 and 128+/-23, respectively; d. Western-blot assay demonstrated that if cells
      were treated with 100 ng/ml rhTARC, the expression of integrin-alpha5 were
      significantly increased (P<0.01), integrin-beta1 level also increased when
      compared with control (P<0.05). CONCLUSION: TARC was expressed specifically at
      human fetal-maternal interface. Trophoblast invasion and migration mainly was
      regulated by up-regulation integrin-alpha5 and integrin-beta1, which plays an
      role in trophoblasts differentiation and placentation.

PMID- 24103121
TI  - [Study on the facial and body terminal hair growth in women in Guangdong by using
      modified Ferriman-Gallwey scoring system].
AB  - OBJECTIVE: To study growth of facial and body terminal hair of women in Guangdong
      province and its relationship with age, menstrual irregularities and polycystic
      ovary, and determine normative cut-off score of modified Ferriman and Gallwey
      (mFG). METHODS: A cross-sectional study was conducted on 2988 women at age of 20
      45 years from 16 communities of two urban and two rural regions in Guangdong
      province from June 2008 to July 2009. Terminal body hair growth was assessed by
      using the modified Ferriman and Gallwey (mFG) scoring system. The normative cut
      off value of mFG were calculated by using the K-means cluster analysis (K=2).
      Those women were classified into following groups, including 982 women at group
      of ages of 20- years, 765 women at group of 26- years, 597 women at group of 31-
      years, 384 women at group of 36- years, 260 women at group of 41-45 years. Due to
      absence or errors of medical records, some cases were excluded from this study.
      Based on menses irregularities (MI), polycystic ovaries (PCO), there were 488
      cases in MI group, 2413 cases in normal menses group, 568 cases in PCO group, and
      2207 cases in non-PCO group finally. The incidences of acne, MI, acanthosis
      nigricans, and polycystic ovaries were also analyzed in all the hirsute groups.
      RESULTS: (1) among 2988 women, it was observed 149 women (5%) with mFG>=7,314
      women (10.5%) with >=5,747 women with mFG>=2. (2) Cluster analysis identified an
      mFG score of 5 as the cut-off value that define abnormal hirsute in the total
      population and all the sub-groups with/without MI or PCO; (3) Based on age
      classification, it was found that increased age was associated with decreased
      trends of the percentile and cut-off value of hirsutism. The value of hirsutism
      of mFG were 6 in group of 20- years, 5 in group of 26- years, 4 in groups of 31-
      years, 36- years and 41-45 years. (4) The prevalence of acne, menstrual
      irregularities and POC were 45.5% (143/314), 73.6% (231/314), 25.8% (81/314) in
      total population, 25.1% (671/2674), 16.1% (431/2674), 19.8% (529/2674) in normal
      hair women, which reached statistical difference (P<0.05). The prevalence of
      acne, menstrual irregularities and acanthosis nigricans were 44.4% (130/293),
      23.2% (68/293), 4.1% (12/293) in those age hirsute groups, 25.3% (681/2695),
      16.2% (437/2695), 1.9% (51/2695) in normal hair women, which reached statistical
      difference (P<0.05). CONCLUSIONS: (1) among women in Guangdong province, mFG
      scoring showed decreased trends in women with increasing age. (2) An mFG score>=5
      was cut-off value in diagnosis of hirsutism. (3) The hirsute women exhibited
      higher incidence of acne, menses irregularity, and acanthosis nigricans than
      those of women with normal hair growth.

PMID- 24103122
TI  - [Application of DHPLC screening TGFBR-3 gene in Chinese women with idiopathic
      premature ovarian failure].
AB  - OBJECTIVE: To evaluate clinical value of denaturing high performance liquid
      chromatography (DHPLC) used in detecting transforming growth factor beta receptor
      3 (TGFBR-3) exons 11 and 12 polymorphism in women with idiopathic premature
      ovarian failure (POF). METHODS: From Feb. 2009 to Dec. 2011, 110 patients with
      idiopathic POF undergoing treatment at Shenzhen Maternal & Child Health Institute
      affiliated to Southern Medical University were enrolled as POF group in this
      study. In the mean time, 110 women under 40 years old with normal hormonal level
      and menstrual cycles as control group. The exons 11 and 12 of TGFBR-3 gene
      polymorphism were screened by using DHPLC, and results of DNA sequencing was as
      golden standard. Some related indexes were calculated, such as sensitivity,
      specificity, false negative value, false positive value, Youden index, positive
      predictive value, and negative predictive value. At the same time, 20% of the
      tested specimens were chosen randomly and detected by DHPLC again. The value of
      Kappa index were calculated by comparing the results between the first and second
      DHPLC analysis. RESULTS: The exon 11 of TGFBR-3 were not identified gene
      polymorphism and two nucleotide polymorphisms were identified in exon 12. For
      2022 T/C polymorphism, the frequencies of CC with 0.9% (1/110), TC with 22.7%
      (25/110), TT with 76.4% (84/110), C with 12.3% (27/220) and T with 87.7%
      (193/220) in POF group were significantly different from CC with 0, TC with 9.1%
      (10/110) and TT with 90.9% (100/110), C with 4.5% (10/220) and T with 95.5%
      (210/220) in control group (all P<0.05). Allelic and genotypic frequencies of
      2161-75 C/T were not differed significantly between the two groups (all P>0.05).
      As DNA sequencing as golden standard, DHPLC showed that the sensitivity was 100%,
      specificity was 97.9%, Youden index was 97.9%, positive predictive value was
      96.3%, negative predictive value was 100%, and Kappa index was 0.888 (P<0.05).
      CONCLUSION: DHPLC analysis is higher validity, reliability and practicability
      method in detecting TGFBR-3 polymorphism in idiopathic premature ovarian failure.

PMID- 24103123
TI  - [Expression and clinical significance of E-cadherin and beta-catenin in the
      vulvar squamous cell carcinoma tissues].
AB  - OBJECTIVE: To investigate the expression of E-cadherin and beta-catenin in the
      Vulvar squamous cell carcinoma (VSCC) tissues. METHODS: A total of 63 documented
      paraffin blocks of VSCC (n=41), vulvar intraepithelial neoplasia (n=22), vulvar
      negative cutting edge tissues (n=10) diagnosed in department of pathology of
      Shengjing Hospital of China Medical University from January 2005 to April 2012
      were enrolled. EliVision immunohistochemical staining was used to detect the
      expression of E-cadherin and beta-catenin in the three groups. Then to do a
      statistical analysis among the expression of them with patients' menopause
      status, pathological grade, clinical stage and lymph node metastasis. Spearman
      correlation analysis was used to analyse the expression of E-cadherin and beta
      catenin in the vulvar lesion tissues. RESULTS: The abnormal immunoreactivity for
      E-cadherin [46%(19/41), 64% (14/22)] and beta-catenin [61% (25/41), 68% (15/22)]
      in VSCC and VINII-III were found, which were significantly different from that in
      normal epithelium samples (P<0.05). The abnormal expression of E-cadherin and
      beta-catenin have no statistically significant difference between VSCC group and
      VINII-III group (P>0.05). The abnormal expression of E-cadherin and beta-catenin
      were collected with tumor pathological grade and lymph node metastasis status
      (all P<0.05). The abnormal expression of E-cadherin and beta-catenin have no
      statistically significant difference between menopause and the surgical stage of
      patients (all P>0.05). The abnormal expression of E-cadherin and beta-catenin
      have a significant positive correlation in the same sample in the VSCC tissue
      (r=0.543, P=0.000). The abnormal expression of E-cadherin and beta-catenin have
      no correlation in the VINII-III tissue (r=0.295, P=0.182). CONCLUSIONS: The
      abnormal expression of E-cadherin and beta-catenin may occurs frequently in the
      VSCC. The abnormal expression of E-cadherin and beta-catenin have correlation
      with vulvar cancer pathological grade and lymph node metastasis, which may be
      important mechanisms promoting the invasion and metastasis of VSCC.

PMID- 24103124
TI  - [Impact of intrauterine device insertion surgery on women's mental state].
AB  - OBJECTIVE: To evaluate the impact of the intrauterine device (IUD) insertion on
      the mental state of women. METHODS: From Jan. 2009 to Jun. 2010, a multi-center
      clinical observational study was performed. Totally 641 women were selected in
      the six provinces' 18 family planning service stations and hospitals for IUD
      insertion surgery study. Analysis of the change of women's mental state which was
      evaluated by symptom checklist-90 (SCL-90) scale before and after IUD insertion
      surgery. RESULTS: Before and after IUD insertion surgery, 10 factors' scores in
      SCL-90 of the observed objects were between 1.1 to 1.2, total scores were 107+/
      27 and 105+/-25, respectively. Before and after surgery, total average score both
      were 1.2, the average score of positive items both were 2.1. The difference of
      the above results were not statistically significance (all P>0.05). Preoperative
      and postoperative, the rate of positive items was 9.2%-19.6% and 7.7%-17.6%,
      respectively.In addition to anxiety and fear, the rate of other factors' positive
      items postoperative was significantly lower than those in the preoperative (all
      P<0.05). The incidence of the observed objects postoperative of each factor
      score, "deteriorated" was in the range of 4.9% to 23.0%, "improved" was in the
      range of 26.3%-50.1%. The incidence of total scores, "deterioration" was 28.8%
      (166/575), "improved" was 45.6% (262/575). The incidence of the average score of
      positive items, "deterioration" was 3.7% (21/575), "improved" was 52.3%
      (301/575). Logistic analysis showed that, in addition to unit level, there were
      no other significant influencing factors for women' mental state of postoperative
      (all P>0.05). CONCLUSION: IUD insertion surgery has no adverse effect on women's
      mental state.

PMID- 24103125
TI  - [Role of epidermal growth factor signaling system in the pathogenesis of
      endometriosis under estrogen deprivation conditions].
AB  - OBJECTIVE: To study the role of epidermal growth factor (EGF) , epidermal growth
      factor receptor(EGFR), extracellular signal-regulated kinase 1/2 (p-ERK1/2) in
      the pathogenesis of endometriosis under estrogen deprivation conditions. METHODS:
      The estrogen was quickly-stripped in medium and the female nude mice were
      castrated by bilateral oophorectomy to build estrogen deprivation in vitro and in
      vivo experimental models, respectively. (1) In vitro experiments:according to
      different treatments the estrogen deprived ectopic endometrial cells were
      classified into 4 groups: a. EGF group:the ectopic endometrial cells were
      cultured for 72 hours with different concentrations of EGF (0.01, 0.1, 1, 10, 50,
      100 ng/ml), the results of EGF group were represented by the result of cells
      treated by 10 ng/ml EGF cultured for 72 hours; b. EGF+PD98059 group:the ectopic
      endometrial cells were cultured for 72 hours with 5*10(-2) mol/L PD98059
      (inhibitor of ERK), followed by a cultivation for 72 hours treated by 10 ng/ml
      EGF+5*10(-2) mol/L PD98059; c. EGF+ ICI182780 group: the ectopic endometrial
      cells were cultured for 72 hours with 10(-6) mol/L ICI182780 [inhibitor of
      estrogen receptor(ER)], followed by a cultivation for 72 hours treated by 10
      ng/ml EGF+10(-6) mol/L ICI182780; d. Blank control group:the ectopic endometrial
      cells were cultured with no treatment. The proliferation activity of ectopic
      endometrial cells in all groups after treatment were examined by methyl thiazolyl
      tetrazolium (MTT) method represented by absorbance value (A). The expression of p
      ERK1/2 protein were detected by western blot. (2) In vivo experiments: 64 female
      nude mice were randomly divided into control and castration groups (both n=32)
      using random number chart. The mice in castration group were castrated by
      bilateral oophorectomy on 3 weeks after the endometriosis model was established.
      The levels of EGF, EGFR, p-ERK1/2 protein in ectopic lesions of both groups were
      measured on 4, 6, 8 and 10 weeks after the endometriosis model was established by
      western blot. RESULTS: (1) The proliferation activity of ectopic endometrial
      cells:the proliferation activity of ectopic endometrial cells treated by
      different concentrations of EGF (0.01, 0.1, 1, 10, 50, 100 ng/ml) for 72 hours
      were 0.310+/-0.010, 0.340+/-0.020, 0.670+/-0.010, 0.980+/-0.030, 1.360+/-0.020,
      1.670+/-0.020, respectively, the proliferation activity was increased along with
      of EGF concentrations.The proliferation activity was 0.680+/-0.030 at EGF+
      PD98059 group, the differences exhibited significant difference when compared
      with that at EGF group with 100 ng/ml for 72 hours (P<0.01) .The proliferation
      activity of EGF+ ICI182780 and blank control groups were 0.330+/-0.030 and
      0.310+/-0.030, respectively, which did not reached statistical differences
      (P>0.05). (2) The expression of EGF, EGFR, pERK1/2 protein: a. In vitro
      experiments:the levels of p-ERK1/2 protein in EGF and blank control groups were
      0.670+/-0.020 and 0.600+/-0.010, respectively, which reached statistical
      differences (P<0.05). The level of p-ERK1/2 protein in EGF+ PD98059 group was
      0.610+/-0.020, which exhibited significant differences with that at blank control
      group (P>0.05). b. In vivo experiments:at 4, 6 and 8 weeks after the
      endometriosis models were established, the expression of EGF protein in the
      ectopic lesions of castration group and control group were (0.530+/-0.015 versus
      0.610+/-0.015), (0.400+/-0.029 versus 0.620+/-0.018), (0.560+/-0.026 versus
      0.630+/-0.021), respectively, the levels of EGFR protein were (0.500+/-0.030
      versus 0.640+/-0.030), (0.470+/-0.020 versus 0.630+/-0.020), (0.510+/-0.030
      versus 0.610+/-0.020) respectively, and the level of p-ERK1/2 protein were
      (0.500+/-0.020 versus 0.580+/-0.020), (0.490+/-0.020 versus 0.580+/-0.020),
      (0.570+/-0.020 versus 0.590+/-0.020), respectively. The difference of EGF, EGFR,
      p-ERK1/2 protein expression levels between two groups did not exhibited
      significant difference (P<0.01, P<0.01, P<0.05). At 10 weeks after the
      endometriosis models were established, the levels of EGF protein in castration
      group and control group were both 0.620+/-0.020, the levels of EGFR protein were
      both 0.610+/-0.020, and the level of p-ERK1/2 protein were 0.590+/-0.010 and
      0.600+/-0.020. No statistical difference (P>0.05) was found between those two
      groups (P>0.05). CONCLUSIONS: EGF could stimulate the proliferation of ectopic
      endometrial cells by activating the ERK pathway under estrogen deprivation
      conditions. The inhibition of EGF signaling system in ectopic lesions was
      alleviated along with the prolongation of the period of estrogen deprivation.

PMID- 24103126
TI  - [Effects of pregnancy on the ROS, NO, cytokine levels and lymphocytes activation
      from mouse peripheral blood].
AB  - OBJECTIVE: To investigate the influence of pregnancy on the production of
      reactive oxygen species (ROS) from mouse peripheral blood neutrophils (PMN), the
      levels of NO and cytokines from serum, the activation of T lymphocytes, and
      initially find the immune regulation effects of pregnancy on the mouse peripheral
      blood lymphocytes. METHODS: Take the BALB/c mice which were at the mid trimester
      of pregnancy (day 14) as the object, full blood staining using ROS probe 2',7'
      dichlorodihydrofluorescein diacetate (H2DCFDA) combing with flow cytometry was
      used to test the levels of ROS from PMN. The production of NO from peripheral
      blood serum were analyzed by Griess kit while the soluble cytokines interleukin
      (IL) 6, IL-10, monocyte chemotactic protein 1 (MCP-1), interferon gamma (IFN
      gamma), tumor necrosis factor alpha (TNF-alpha) and IL-12 were detected by liquid
      protein quantitative technology cytometric bead array (CBA) using flow cytometry.
      The activation of peripheral blood lymphocytes at early, middle and later phases
      which marked with CD69, CD25 and CD71 respectively were tested by flow cytometry
      and two-color fluorescent staining. RESULTS: Comparing to the normal non-pregnant
      mouse, pregnancy obviously promoted the production of ROS from PMN (101.1+/-2.2
      versus 134.5+/-10.3, P<0.05). Comparing to the normal non-pregnant mouse,
      pregnancy obviously promoted the secretion of NO [(22.7+/-0.7) versus (36.3+/
      1.2) umol/L, P<0.01]. In normal non-pregnant mouse, the serum levels of IL-6, IL
      10, MCP-1, IFN-gamma, TNF-alpha and IL-12 were (9.3+/-0.5), (26.7+/-0.9), (21.2+/
      1.6), (14.5+/-1.8), (22.6+/-1.6) and (8.4+/-1.2) pg/ml, while in pregnancy group
      the levels were (26.5+/-1.0), (40.4+/-2.5), (25.1+/-0.7), (457.4+/-17.9), (93.2+/
      4.3) and (7.5+/-0.9) pg/ml correspondingly; the levels of IL-6, IFN-gamma, TNF
      alpha from peripheral blood serum (P<0.01), while had no effects on the
      production of IL-10 and MCP-1 (P>0.05). About the CD+3 T lymphocytes activation,
      in normal non-pregnant mouse, the CD69, CD25 and CD71 expression rate were
      (0.43+/-0.15)%, (5.13+/-0.25)% and (0.37+/-0.11)%, while in pregnancy group the
      CD69, CD25 and CD71 expression rate were (0.40+/-0.10)%, (6.17+/-0.40)% and
      (6.10+/-0.31)%. The levels of middle and later phases markers as CD25 and CD71
      were highly up-regulated (P<0.05), while the early phase action CD69 had no
      obvious variation (P>0.05). CONCLUSION: The mid trimester of pregnancy promoted
      the production of ROS from PMN, the levels of NO, IL-6, IFN-gamma, TNF-alpha from
      peripheral blood serum, and the middle- and later-phase activation of T
      lymphocytes.

PMID- 24103127
TI  - Continuous exposure to dizocilpine facilitates escalation of cocaine consumption
      in male Sprague-Dawley rats.
AB  - BACKGROUND: Although the escalation of cocaine consumption is a hallmark of
      cocaine dependence, the neurobiological mechanisms that underlie this change in
      behavior are not well understood. METHODS: This study used an extended access
      version of the drug self-administration procedure to explore how N-methyl-d
      aspartate (NMDA) receptors are involved in escalation of cocaine consumption.
      Male Sprague-Dawley rats (n=59) were first trained to self-administer cocaine
      (0.33 mg/infusion, i.v.) under a fixed-ratio 1 (FR1) schedule of reinforcement.
      After training, rats were implanted with subcutaneous osmotic minipumps filled
      with vehicle or the non-competitive NMDAR antagonist, dizocilpine (0.2 or 0.4
      mg/kg/d), and subsequently allowed to self-administer cocaine in 2h or 6h self
      administration sessions. RESULTS: In the 6h groups, vehicle-treated rats
      escalated cocaine self-administration across 15 self-administration sessions;
      rats treated with dizocilpine escalated cocaine self-administration at a greater
      rate and to a greater degree. Rats that self-administered cocaine during 2h
      sessions did not escalate consumption of cocaine under any treatment condition.
      Discontinuation of dizocilpine treatment in the 6h access condition led to a
      substantial decrease in cocaine consumption, down to pre-escalation levels, and
      then control rates of escalation thereafter. Despite large differences in intake
      under the FR1 schedule, post-escalation break point under a progressive ratio
      schedule of reinforcement did not differ between groups. CONCLUSION: These data
      suggest that glutamate tone through NMDA receptors can play a dynamic role in
      regulating cocaine intake and escalation of consumption.

PMID- 24103128
TI  - Scaling up HIV prevention efforts targeting people who inject drugs in Central
      Asia: a review of key challenges and ways forward.
AB  - BACKGROUND: In Central Asia, between 33% and 72% of cumulative HIV infections has
      been attributed to unsafe injection practices among people who inject drugs
      (PWID). METHODS: We reviewed the current status and trends of national efforts in
      Central Asian countries to control HIV among PWID, and also reviewed the key
      structural and health-systems-related challenges that facilitate drug-use-related
      HIV risk in Central Asia. RESULTS: The spectrum and scale of HIV prevention
      services targeting PWID vary considerably among Central Asian countries. In all
      countries, the potential impact of these interventions is hindered by several key
      features: a restrictive legal environment, poor performance of service providers,
      widespread opposition to harm reduction, deficient human resources and funding
      mechanisms, poor services integration, insufficient community involvement, and
      other structural factors. CONCLUSIONS: Scaling up HIV prevention interventions in
      Central Asia will demand greater attention to the structural, health-care-related
      and social factors that facilitate HIV risk and impede service utilization among
      PWID. Multi-level combination prevention interventions should be developed with a
      focus on the sexual partners and risk networks of PWID, aiming at early detection
      of HIV, timely enrollment in HIV care, and retention in HIV care.

PMID- 24103129
TI  - Sorghum mutant RG displays antithetic leaf shoot lignin accumulation resulting in
      improved stem saccharification properties.
AB  - BACKGROUND: Improving saccharification efficiency in bioenergy crop species
      remains an important challenge. Here, we report the characterization of a Sorghum
      (Sorghum bicolor L.) mutant, named REDforGREEN (RG), as a bioenergy feedstock.
      RESULTS: It was found that RG displayed increased accumulation of lignin in
      leaves and depletion in the stems, antithetic to the trend observed in wild type.
      Consistent with these measurements, the RG leaf tissue displayed reduced
      saccharification efficiency whereas the stem saccharification efficiency
      increased relative to wild type. Reduced lignin was linked to improved
      saccharification in RG stems, but a chemical shift to greater S:G ratios in RG
      stem lignin was also observed. Similarities in cellulose content and structure by
      XRD-analysis support the correlation between increased saccharification
      properties and reduced lignin instead of changes in the cellulose composition
      and/or structure. CONCLUSION: Antithetic lignin accumulation was observed in the
      RG mutant leaf-and stem-tissue, which resulted in greater saccharification
      efficiency in the RG stem and differential thermochemical product yield in high
      lignin leaves. Thus, the red leaf coloration of the RG mutant represents a
      potential marker for improved conversion of stem cellulose to fermentable sugars
      in the C4 grass Sorghum.

PMID- 24103130
TI  - Insights into subunit interactions in the Sulfolobus acidocaldarius archaellum
      cytoplasmic complex.
AB  - Archaella are the archaeal motility structure that is the functional pendant of
      the bacterial flagellum but is assembled by a mechanism similar to that for type
      IV pili. Recently, it was shown by Banerjee et al. that FlaX, a crenarchaeal
      archaellum subunit from Sulfolobus acidocaldarius, forms a ring-like oligomer,
      and it was proposed that this ring may act as a static platform for torque
      generation in archaellum rotation [Banerjee A et al. (2012) J Biol Chem 287,
      43322-43330]. Moreover, the hexameric crystal structure of FlaI was solved, and
      its dual function in the assembly and the rotation of the archaellum was
      demonstrated [Reindl S et al. (2013) Mol Cell 49, 1069-1082]. In this study, we
      show by biochemical and biophysical techniques that FlaX from S. acidocaldarius
      acts as a cytoplasmic scaffold in archaellum assembly, as it interacts with FlaI
      as well as with the recA family protein FlaH, the only cytoplasmic components of
      the archaellum. Interaction studies using various truncated versions of FlaI
      demonstrated that its N- and C-termini interact with FlaX. Moreover, using
      microscale thermophoresis, we show that FlaI, FlaX and FlaH interact with high
      affinities in the nanomolar range. Therefore, we propose that these three
      proteins form the cytoplasmic motor complex of the archaellum.

PMID- 24103131
TI  - [Van Heerden: the first female doctor in South Africa].
AB  - Petronella van Heerden (1887-1975) was born in South Africa. She studied medicine
      in Amsterdam from 1908 to 1915 and then worked as the first female doctor in her
      native country for 4 years before specialising in gynaecology in London. She then
      returned to Amsterdam, where she gained a PhD in 1923 on a thesis on
      endometriosis that was written in Afrikaans. She settled in Cape Town and
      participated in many political and emancipatory activities alongside her work as
      a doctor. She wrote two autobiographies. 

PMID- 24103132
TI  - [Diagnostic and therapeutic strategies for the management of severe mitral valve
      regurgitation].
AB  - Mitral regurgitation is the second most frequent valvular heart disease.
      Echocardiography is the principal examination to determine severity, mechanism
      and hemodynamic consequences of mitral regurgitation and consequently contributes
      to the assessment and accurate timing of the best treatment strategy. To clarify
      clinical decision making in severe mitral regurgitation, this review will discuss
      the diagnostic work-up and treatment options according to the most recent
      guidelines. Mitral valve surgery, preferably repair, is indicated in symptomatic
      patients with severe, organic mitral regurgitation. Chronic, functional mitral
      regurgitation is often medically treated (including cardiac resynchronization
      therapy if indicated), however surgery (preferably annuloplasty) can be
      recommended. Percutaneous MitraClip-implantation may be considered as an
      alternative option in symptomatic patients with severe mitral regurgitation who
      are considered inoperable. At present, there is no consensus on the optimal care
      in asymptomatic patients with severe, organic mitral regurgitation and preserved
      left ventricular function. A prospective trial is highly needed to elucidate this
      best treatment strategy.

PMID- 24103133
TI  - [Combination therapy for hypertension].
AB  - The average systolic blood pressure-lowering effect of antihypertensive
      monotherapy is no more than 9.1 mmHg and for the diastolic value, 5.5 mmHg. Due
      to the limited effect of monotherapy, 2 or more antihypertensive agents are
      required in at least two-third of the hypertensive population. Because of their
      complementary blood pressure-lowering mechanisms and proven efficacy, it is
      advisable to initiate a combination of a renin-angiotensin-system (RAS) blocking
      agent with a RAS-independent agent; the choice of initial agents depends on age,
      ethnicity and co-morbidity. It is preferable that treatment is started using a
      stepwise approach: 1 agent is started and a second or third agent is added to the
      regimen. If the patient's actual blood pressure exceeds the target value by more
      than 20/10 mmHg, an alternative approach would be to start immediately with 2
      agents. Compliance to therapy and the continuation of antihypertensive treatment
      are notoriously poor; treatment using a combination preparation containing 2 or
      even 3 different components is therefore preferred.

PMID- 24103134
TI  - [Congenital CMV infections].
AB  - Only 10-15% of neonates with congenital cytomegalovirus infection have symptoms
      at birth. The most common symptoms are intrauterine growth retardation,
      microcephaly, petechiae, jaundice, hepatosplenomegaly, intracranial
      abnormalities, ophthalmological abnormalities and hearing loss. Symptomatic and
      asymptomatic CMV infections can both have long-term effects. CMV infection during
      pregnancy is diagnosed using a blood test and possible testing of the amniotic
      fluid for viral DNA. Infection of the fetus may be prevented by treating the
      mother with CMV hyperimmune globulin. In the neonate a diagnosis can be made by
      viral culture or PCR in urine. PCR in saliva could be an alternative. Blood
      testing is of limited value. If symptoms of CMV infection occur in the neonate,
      such as petechiae, microcephaly, central nervous system abnormalities,
      sensorineural hearing loss or chorioretinitis, antiviral treatment should be
      considered. Long-term follow-up is advisable because of the possibility of
      delayed-onset hearing loss and chorioretinitis.

PMID- 24103135
TI  - [Increased CK activity in serum without symptoms: further investigations often
      unnecessary].
AB  - Increased activity of the enzyme creatine kinase (CK) in serum is not
      infrequently encountered in routine diagnostic laboratory investigations.
      Patients are often referred to a neurologist specialized in neuromuscular
      disorders for evaluation. However, as in many cases hyperCKemia is physiological
      or results from physical activity or muscle trauma, further investigations are
      often unnecessary. We report four cases of hyperCKemia, two of which were
      physiological or due to non-neuromuscular factors (medication, physical
      activity). In the other two patients, the hyperCKemia was the first recognized
      sign of an underlying neuromuscular disorder. In these two cases, specific
      aspects of the history or physical examination prompted further investigations.
      We discuss various physiological and other non-neuromuscular factors that may
      cause hyperCKemia. It is important to recognize these causes before referral to a
      neurologist with neuromuscular expertise. We present guidelines for ancillary
      investigations by general practitioners or specialists. 

PMID- 24103136
TI  - [A women with an altered defaecation pattern].
AB  - A 74-year-old woman went to the gastroenterologist because of an altered
      defaecation pattern. Colonoscopy could not be completed due to sigmoid
      angulation. A CT-scan of the colon showed that the colon was located in the left
      side of the abdomen, as a result of embryonic non-rotation of the intestine. In
      adults this is generally asymptomatic. Non-specific abdominal complaints or
      volvulus seldom occur. Surgical intervention is rarely necessary. 

PMID- 24103137
TI  - [Volume replacement therapy; what is the solution?].
AB  - 2 types of infusion solutions are used for volume replacement: crystalline fluids
      (such as NaCl 0.9% and lactated Ringer's solution) and colloidal fluids made of
      hydroxyethyl cellulose, albumin or gelatine. The choice of fluids used appears to
      be determined by the personal preference of the physician or the department.
      Infusion of colloidal solutions results in rapid recovery of the circulating
      volume but can cause anaphylaxis, renal insufficiency and an increased bleeding
      tendency. The use of hydroxyethyl cellulose (HEC) is associated with higher
      mortality and renal impairment, and is therefore not very justifiable. Albumin
      based infusions appear to be predominantly indicated for septic patients with
      hypoalbuminaemia. Gelatin-based infusion fluids have not yet been extensively
      studied. The balanced lactated Ringer's solution, the composition of which is
      closer to plasma than that of NaCl 0.9%, is being used with ever-increasing
      frequency. Lactated Ringer's infusion solution does not cause hyperchloremic
      acidosis and probably less often leads to renal insufficiency than when NaCl 0.9%
      is infused.

PMID- 24103138
TI  - [White matter abnormalities following attempted suicide].
AB  - BACKGROUND: Delayed post-hypoxic leukoencephalopathy (DPHL) is a demyelinating
      disorder characterized by neuropsychiatric symptoms occurring a few days to some
      weeks following cerebral hypoxia. CASE DESCRIPTION: A 50-year old female patient
      showed rapidly progressive cognitive deterioration with apathy, mutism and
      regressive behaviour a few weeks after a suicide attempt with carbon monoxide
      (CO). This eventually leads to a state of akinetic mutism. Magnetic resonance
      imaging (MRI) of the brain showed diffuse white matter abnormalities. These MRI
      findings combined with CO intoxication and the clinical picture were highly
      suggestive for DPHL. CONCLUSION: This case emphasizes that a neurological cause
      should be considered if rapidly progressive neuropsychiatric symptoms occur, and
      that after suspected auto intoxication it is important to take possible hypoxia
      and its after-effects into consideration. Recognition of DPHL is important so
      that unnecessary invasive diagnostics and treatment can be avoided. Considering
      the favorable natural course of DPHL appropriate measures should be taken in
      order to provide supportive care and rehabilitation.

PMID- 24103139
TI  - [Pregnancy after isotretinoin use].
AB  - BACKGROUND: Acne is a common problem that is increasingly being effectively
      treated with isotretinoin, a highly teratogenic agent. According to the pregnancy
      prevention program, contraception should be used until at least one month after
      discontinuing the medication. CASE DESCRIPTION: A 29-year-old woman became
      pregnant shortly after discontinuing isotretinoin. She was referred to the
      gynaecologist for an abortion. However, since she wished to continue the
      pregnancy, she received personal advice on the risk of bearing a child with
      congenital abnormalities. After an uneventful pregnancy she gave birth to a
      healthy son. CONCLUSION: Given the teratogenicity of isotretinoin, every woman in
      the fertile phase of life should use contraception while taking the medication.
      If she becomes pregnant, however, the individual risk of having a child with
      congenital abnormalities can be carefully and reliably estimated by determining
      the precise date of conception through ultrasound and the date that isotretinoin
      was stopped.

PMID- 24103140
TI  - [A woman with a growing mass near the anus].
AB  - A 58-year-old woman visited the surgical outpatient clinic because of a mass near
      the anus that had existed for years and had now grown to a size that made sitting
      impossible. With histological examination of the 6 x 10 cm exofytic, condylomatic
      mass, the diagnosis 'giant condyloma acuminatum' was made. Radical excision was
      performed, the patient recovered well. 

PMID- 24103141
TI  - Safety of once-daily insulin detemir in patients with type 2 diabetes treated
      with oral hypoglycemic agents in routine clinical practice.
AB  - BACKGROUND: The aim of the present study was to identify demographic and
      treatment factors that were predictive of hypoglycemia in a large cohort of type
      2 diabetic patients initiating insulin detemir. METHODS: The present 24-week
      observational study of insulin initiation included 17 374 participants from 10
      countries. Severe hypoglycemia was defined as an event requiring third party
      assistance; minor hypoglycemia was defined as a daytime or nocturnal glucose
      measurement <3.1 mmol/L. RESULTS: Prior to initiating insulin therapy, 4.9% of
      the cohort reported hypoglycemia (pre-insulin hypoglycemia), with most (94.2%)
      reporting minor events and 9.6% reporting severe events. Compared with patients
      without pre-insulin hypoglycemia, those with pre-insulin hypoglycemia had a
      higher incidence of events of minor hypoglycemia (1.72 vs 4.46 events per patient
      year [ppy], respectively), nocturnal hypoglycemia (0.25 vs 1.09 events ppy,
      respectively), and severe hypoglycemia (<0.01 vs 0.04 events ppy, respectively)
      at final visit. Age (P < 0.047), body mass index (P < 0.001), a prior history of
      microvascular disease (P < 0.001), pre-insulin hypoglycemia (P < 0.001),
      increased number of oral hypoglycemic agents (OHAs; P < 0.001), OHA
      intensification (P < 0.001), and the use of glinides (P = 0.004) were all found
      to be independently associated with the occurrence of hypoglycemia during the
      study. CONCLUSIONS: Once-daily insulin detemir therapy was safe and effective,
      and rates of hypoglycemia were low. Concerns about hypoglycemia should not deter
      the initiation of basal insulin analogs.

PMID- 24103142
TI  - Mucormycosis as a rare cause of severe gastrointestinal bleeding after
      multivisceral transplantation.
AB  - Mucormycosis, an emerging fungal infection in solid organ transplant patients, is
      mostly located in rhino-orbito-cerebral, pulmonary, and cutaneous areas, or
      disseminated with poor prognosis. A 4-year-old girl with chronic intestinal
      pseudo-obstruction syndrome underwent a modified multivisceral transplantation,
      including half of the stomach, the duodeno-pancreas, the small bowel, and the
      right colon. On postoperative day 5, a digestive perforation was suspected.
      Surgical exploration found a small necrotic area on the native stomach, which was
      externally drained. The next day, massive gastric bleeding occurred. During the
      emergency laparotomy, 2 hemorrhagic ulcers were found and resected from the
      transplanted stomach. Pathology and fungal culture showed mucormycosis caused by
      Lichtheimia (formerly Absidia) ramosa in both the transplanted and native
      stomach. High-dose intravenous liposomal amphotericin B was immediately started.
      No other site of fungal infection was found. The child recovered, and 3 years
      after transplantation, is alive and well, off parenteral nutrition. The
      originality of this case is the very early presentation after transplantation,
      the unusual site, and the complete recovery after rapid medico-surgical
      management. The origin of the fungus and treatment are discussed. 

PMID- 24103143
TI  - Neuropsychological performance in children with temporal lobe epilepsy having
      normal MRI findings.
AB  - BACKGROUND AND AIMS: Most information on the neuropsychological performance of
      pediatric patients with temporal lobe epilepsy (TLE) is derived from selected
      surgical series. Non-lesional pediatric TLE patients were studied here at the
      population level in order to investigate the extent to which neuropsychological
      deficits predisposing to learning difficulties exist in this more common group.
      METHODS: Language, memory and executive functions were measured in children aged
      8-15 years with non-lesional TLE and of normal intelligence (n = 21), and their
      performance was compared with that of healthy age and gender-matched children (n
      = 21). The effects of clinical epilepsy variables on performance were examined.
      RESULTS: Although neuropsychological performance did not differ between the TLE
      patients and the healthy controls, female gender, early onset, longer duration
      and abnormal interictal EEG had a negative effect on neuropsychological
      performance. CONCLUSIONS: Children with early-onset epilepsy should be assessed
      carefully for neuropsychological impairment using sufficiently broad batteries of
      tests in order to detect even slight deficits. Our sample size was small and
      these findings should be interpreted as preliminary results and need to be
      confirmed in larger studies.

PMID- 24103144
TI  - Identification of brain tumour initiating cells using the stem cell marker
      aldehyde dehydrogenase.
AB  - Aldehyde dehydrogenase (ALDH) has been identified in stem cells from both normal
      and cancerous tissues. This study aimed to evaluate the potential of ALDH as a
      universal brain tumour initiating cell (BTIC) marker applicable to primary brain
      tumours and their biological role in maintaining stem cell status. Cells from
      various primary brain tumours (24paediatric and 6 adult brain tumours) were
      stained with Aldefluor and sorted by flow cytometry. We investigated the impact
      of ALDH expression on BTIC characteristics in vitro and on tumourigenic potential
      in vivo. Primary brain tumours showed universal expression of ALDH, with 0.3
      28.9% of the cells in various tumours identified as ALDH(+). The proportion of
      CD133(+) cells within ALDH(+) is higher than ALDH cells. ALDH(+) cells generate
      neurospheres with high proliferative potential, express neural stem cell markers
      and differentiate into multiple nervous system lineages. ALDH(+) cells tend to
      show high expression of induced pluripotent stem cell-related genes. Notably,
      targeted knockdown of ALDH1 by shRNA interference in BTICs potently disturbed
      their self-renewing ability. After 3months, ALDH(+) cells gave rise to tumours in
      93% of mice whereas ALDH cells did not. The characteristic pathology of mice
      brain tumours from ALDH(+) cells was similar to that of human brain tumours, and
      these cells are highly proliferative in vivo. Our data suggest that primary brain
      tumours contain distinct subpopulations of cells that have high expression levels
      of ALDH and BTIC characteristics. ALDH might be a potential therapeutic target
      applicable to primary brain tumours. 

PMID- 24103145
TI  - The clinical utility of the local inflammatory response in colorectal cancer.
AB  - BACKGROUND: The host immune response is important in the prevention of tumour
      progression in solid organ cancers. The aim was to evaluate the clinical utility
      of the local inflammatory response in patients with colorectal cancer. METHODS:
      Three hundred and sixty-five patients with primary operable colorectal cancer
      were included. The local inflammatory response was assessed using three different
      methods; (1) individual T-cell subtypes (CD3, CD8, CD45R0, FOXP3), (2) an
      immunohistochemistry-based immune score (Galon Immune Score) and (3) a
      histopathological assessment (Klintrup-Makinen grade). Relationships with tumour
      and host characteristics were established and the prognostic value of each method
      compared. RESULTS: A strong infiltration of tumour infiltrating lymphoctyes
      (TIL's) was associated with improved cancer-specific survival. When individual T
      cell subtypes were considered, CD3-positive cells were the strongest predictor of
      survival at the invasive margin (CD3(+) IM) while CD8-positive cells were the
      strongest predictor in the cancer cell nests (CD8(+) CCN). Infiltration of T
      cells was related to early tumour stage, expanding growth pattern and lower
      levels of venous invasion but was not influenced by host characteristics or
      degree of systemic inflammation. In summary, CD3(+) IM, CD8(+) CCN, The Galon
      Immune Score and the Klintrup-Makinen grade all exhibited similar survival
      relationships in both node-positive and node-negative colorectal cancer.
      CONCLUSION: A coordinated adaptive immune response is an important factor in
      predicting outcome in patients with primary operable colorectal cancer. By
      comparing different methodologies we have provided a foundation on which to
      develop a standardised approach for assessing the local inflammatory response in
      these patients.

PMID- 24103146
TI  - Quantitative and qualitative analysis of study-related patient information sheets
      in randomised neuro-oncology phase III-trials.
AB  - INTRODUCTION: In randomised controlled trials (RCTs), patient informed consent
      documents are an essential cornerstone of the study flow. However, these
      documents are often oversized in format and content. Clinical experience suggests
      that study information sheets are often not used as an aid to decision-making due
      to their complexity. MATERIAL AND METHODS: We analysed nine patient informed
      consent documents from clinical neuro-oncological phase III-studies running at a
      German Brain Tumour Centre with the objective to investigate the quality of these
      documents. Text length, formal layout, readability, application of ethical and
      legal requirements, scientific evidence and social aspects were used as rating
      categories. Results were assessed quantitatively by two independents
      investigators and were depicted using net diagrams. RESULTS: All patient informed
      consent documents were of insufficient quality in all categories except that
      ethical and legal requirements were fulfilled. Notably, graduate levels were
      required to read and understand five of nine consent documents. DISCUSSION:
      Quality deficits were consistent between the individual study information texts.
      Irrespective of formal aspects, a document that is intended to inform and
      motivate patients to participate in a study needs to be well-structured and
      understandable. We therefore strongly mandate to re-design patient informed
      consent documents in a patient-friendly way. Specifically, standardised
      components with a scientific foundation should be provided that could be
      retrieved at various times, adapted to the mode of treatment and the patient's
      knowledge, and could weigh information dependent of the stage of treatment
      decision.

PMID- 24103150
TI  - Analysis of Tomato spotted wilt virus NSs protein indicates the importance of the
      N-terminal domain for avirulence and RNA silencing suppression.
AB  - Recently, Tomato spotted wilt virus (TSWV) nonstructural protein NSs has been
      identified unambiguously as an avirulence (Avr) determinant for Tomato spotted
      wilt (Tsw)-based resistance. The observation that NSs from two natural resistance
      breaking isolates had lost RNA silencing suppressor (RSS) activity and Avr
      suggested a link between the two functions. To test this, a large set of NSs
      mutants was generated by alanine substitutions in NSs from resistance-inducing
      wild-type strains (NSs(RI) ), amino acid reversions in NSs from resistance
      breaking strains (NSs(RB)), domain deletions and swapping. Testing these mutants
      for their ability to suppress green fluorescent protein (GFP) silencing and to
      trigger a Tsw-mediated hypersensitive response (HR) revealed that the two
      functions can be separated. Changes in the N-terminal domain were found to be
      detrimental for both activities and indicated the importance of this domain,
      additionally supported by domain swapping between NSs(RI) and NSs(RB). Swapping
      domains between the closely related Tospovirus Groundnut ringspot virus (GRSV)
      NSs and TSWV NSs(RI) showed that Avr functionality could not simply be
      transferred between species. Although deletion of the C-terminal domain rendered
      NSs completely dysfunctional, only a few single-amino-acid mutations in the C
      terminus affected both functions. Mutation of a GW/WG motif (position 17/18)
      rendered NSs completely dysfunctional for RSS and Avr activity, and indicated a
      putative interaction between NSs and Argonaute 1 (AGO1), and its importance in
      TSWV virulence and viral counter defence against RNA interference.

PMID- 24103151
TI  - Genetic diversities of cytochrome B in Xinjiang Uyghur unveiled its origin and
      migration history.
AB  - BACKGROUND: Uyghurs are one of the many populations of Central Eurasia that is
      considered to be genetically related to Eastern and Western Eurasian populations.
      However, there are some different opinions on the relative importance of the
      degree of Eastern and Western Eurasian genetic influence. In addition, the
      genetic diversity of the Uyghur in different geographic locations has not been
      clearly studied. RESULTS: In this study, we are the first to report on the DNA
      polymorphism of cytochrome B in the Uyghur population located in Xinjiang in
      northwest China. We observed a total of 102 mutant sites in the 240 samples that
      were studied. The average number of mutated nucleotides in the samples was 5.126.
      A total of 93 different haplotypes were observed. The gene diversity and
      discrimination power were 0.9480 and 0.9440, respectively. There were founder and
      bottleneck haplotypes observed in Xinjiang Uyghurs. Xinjiang Uyghurs are more
      genetically related to Chinese population in genetics than to Caucasians.
      Moreover, there was genetic diversity between Uyghurs from the southern and
      northern regions. There was significance in genetic distance between the southern
      Xinjiang Uyghurs and Chinese population, but not between the northern Xinjiang
      Uyghurs and Chinese. The European vs. East Asian contribution to the ten regional
      Uyghur groups varies among the groups and the European contribution to the Uyghur
      increases from north to south geographically. CONCLUSION: This study is the first
      report on DNA polymorphisms of cytochrome B in the Uyghur population. The study
      also further confirms that there are significant genetic differences among the
      Uyghurs in different geographical locations.

PMID- 24103152
TI  - The clinical measurement, measurement method and experimental condition
      ontologies: expansion, improvements and new applications.
AB  - BACKGROUND: The Clinical Measurement Ontology (CMO), Measurement Method Ontology
      (MMO), and Experimental Condition Ontology (XCO) were originally developed at the
      Rat Genome Database (RGD) to standardize quantitative rat phenotype data in order
      to integrate results from multiple studies into the PhenoMiner database and data
      mining tool. These ontologies provide the framework for presenting what was
      measured, how it was measured, and under what conditions it was measured.
      RESULTS: There has been a continuing expansion of subdomains in each ontology
      with a parallel 2-3 fold increase in the total number of terms, substantially
      increasing the size and improving the scope of the ontologies. The proportion of
      terms with textual definitions has increased from ~60% to over 80% with greater
      synchronization of format and content throughout the three ontologies.
      Representation of definition source Uniform Resource Identifiers (URI) has been
      standardized, including the removal of all non-URI characters, and systematic
      versioning of all ontology files has been implemented. The continued expansion
      and success of these ontologies has facilitated the integration of more than
      60,000 records into the RGD PhenoMiner database. In addition, new applications of
      these ontologies, such as annotation of Quantitative Trait Loci (QTL), have been
      added at the sites actively using them, including RGD and the Animal QTL
      Database. CONCLUSIONS: The improvements to these three ontologies have been
      substantial, and development is ongoing. New terms and expansions to the
      ontologies continue to be added as a result of active curation efforts at RGD and
      the Animal QTL database. Use of these vocabularies to standardize data
      representation for quantitative phenotypes and quantitative trait loci across
      databases for multiple species has demonstrated their utility for integrating
      diverse data types from multiple sources. These ontologies are freely available
      for download and use from the NCBO BioPortal website at
      http://bioportal.bioontology.org/ontologies/1583 (CMO),
      http://bioportal.bioontology.org/ontologies/1584 (MMO), and
      http://bioportal.bioontology.org/ontologies/1585 (XCO), or from the RGD ftp site
      at ftp://rgd.mcw.edu/pub/ontology/.

PMID- 24103153
TI  - ZnO nanoneedle/H2O solid-liquid heterojunction-based self-powered ultraviolet
      detector.
AB  - ZnO nanoneedle arrays were grown vertically on a fluorine-doped tin oxide-coated
      glass by hydrothermal method at a relatively low temperature. A self-powered
      photoelectrochemical cell-type UV detector was fabricated using the ZnO
      nanoneedles as the active photoanode and H2O as the electrolyte. This solid
      liquid heterojunction offers an enlarged ZnO/water contact area and a direct
      pathway for electron transport simultaneously. By connecting this UV
      photodetector to an ammeter, the intensity of UV light can be quantified using
      the output short-circuit photocurrent without a power source. High
      photosensitivity, excellent spectral selectivity, and fast photoresponse at zero
      bias are observed in this UV detector. The self-powered behavior can be well
      explained by the formation of a space charge layer near the interface of the
      solid-liquid heterojunction, which results in a built-in potential and makes the
      solid-liquid heterojunction work in photovoltaic mode. 

PMID- 24103154
TI  - The expanding role of yeast in cancer research and diagnosis: insights into the
      function of the oncosuppressors p53 and BRCA1/2.
AB  - When the glucose supply is high, despite the presence of oxygen, Saccharomyces
      cerevisiae uses fermentation as its main metabolic pathway and switches to
      oxidative metabolism only when this carbon source is limited. There are
      similarities between glucose-induced repression of oxidative metabolism of yeast
      and metabolic reprogramming of tumor cells. The glucose-induced repression of
      oxidative metabolism is regulated by oncogene homologues in yeast, such as RAS
      and Sch9p, the yeast homologue of Akt. Yeast also undergoes an apoptosis-like
      programmed cell death process sharing several features with mammalian apoptosis,
      including oxidative stress and a major role played by mitochondria. Evasion of
      apoptosis and sustained proliferative signaling are hallmarks of cancer. This,
      together with the possibility of heterologous expression of human genes in yeast,
      has allowed new insights to be obtained into the function of mammalian
      oncogenes/oncosuppressors. Here, we elaborate on the similarities between tumor
      and yeast cells underpinning the use of this model organism in cancer research.
      We also review the achievements obtained through heterologous expression in yeast
      of p53, BRCA1, and BRCA2, which are among the best-known cancer-susceptibility
      genes, with the aim of understanding their role in tumorigenesis. Yeast-cell
      based functional assays for cancer genetic testing will also be dealt with. 

PMID- 24103156
TI  - Beliefs about voices and schemas about self and others in psychosis.
AB  - BACKGROUND: In people who experience auditory verbal hallucinations, beliefs the
      person holds about their voices appear to be clinically important as mediators of
      associated distress and disability. Whilst such beliefs are thought to be
      influenced by broader schematic representations the person holds about themselves
      and other people, there has been little empirical examination of this, in
      particular in relation to beliefs about voice intent and the personal meaning of
      the voice experience. METHOD: Thirty-four voice hearers with a diagnosis of
      schizophrenia or schizoaffective disorder completed the Psychotic Symptom Rating
      Scales and measures of beliefs about voices (Revised Beliefs About Voices
      Questionnaire, Interpretation of Voices Inventory) and schemas (Brief Core Schema
      Scales). RESULTS: Beliefs about voices were correlated with both negative voice
      content and schemas. After controlling for negative voice content, schemas were
      estimated to predict between 9% and 35% of variance in the six beliefs about
      voices that were measured. Negative-self schemas were the strongest predictors,
      and positive-self and negative-other schemas also showed potential relationships
      with beliefs about voices. CONCLUSIONS: Schemas, particularly those regarding the
      self, are potentially important in the formation of a range of clinically
      relevant beliefs about voices.

PMID- 24103157
TI  - Crestal Bone Stability around Implants with Horizontally Matching Connection
      after Soft Tissue Thickening: A Prospective Clinical Trial.
AB  - BACKGROUND: It has been shown that thin mucosal tissues may be an important
      factor in crestal bone loss etiology. Thus, it is possible that mucosal tissue
      thickening with allogenic membrane might reduce crestal bone loss. PURPOSE: The
      purpose of this study was to evaluate how implants with traditional connection
      maintain crestal bone level after soft tissue thickening with allogenic membrane.
      MATERIALS AND METHODS: One hundred three patients received 103 internal hex
      implants of 4.6 mm diameter with regular connection. According to gingiva
      thickness, patients were assigned into A (thin tissues, n = 34), B (thin,
      thickened with allogenic membrane, n = 35), and C group (thick tissues, n = 34).
      Groups A and C had one-stage approach, and in group B, implants were placed in
      two stages. Radiographic examination was performed after implant placement, 2
      months after healing, after restoration, and after 1-year follow-up. Crestal bone
      loss was calculated medially and distally. Significance was set to 0.05. RESULTS:
      After 1-year follow-up, implants in group A had 1.65 +/- 0.08-mm bone loss
      mesially and 1.81 +/- 0.06 mm distally. Group B had 0.31 +/- 0.05 mm mesially and
      0.34 +/- 0.05 mm distally. C group implants experienced bone loss of 0.44 +/-
      0.06 mm mesially and 0.47 +/- 0.07 mm distally. Differences between A and B, and
      A and C were significant (p = .000) both mesially and distally, whereas
      differences between B and C were not significant mesially (p = .166) and distally
      (p = .255). CONCLUSIONS: It can be concluded that thin mucosal tissues may cause
      early crestal bone loss, but their thickening with allogenic membrane may
      significantly reduce bone resorption. Implants in naturally thick soft tissues
      experienced minor bone remodeling.

PMID- 24103158
TI  - Comprehensive assessment and standardization of solid phase multiplex-bead arrays
      for the detection of antibodies to HLA-drilling down on key sources of variation.

PMID- 24103155
TI  - Genetic approaches to understanding post-traumatic stress disorder.
AB  - Post-traumatic stress disorder (PTSD) is increasingly recognized as both a
      disorder of enormous mental health and societal burden, but also as an anxiety
      disorder that may be particularly understandable from a scientific perspective.
      Specifically, PTSD can be conceptualized as a disorder of fear and stress
      dysregulation, and the neural circuitry underlying these pathways in both animals
      and humans are becoming increasingly well understood. Furthermore, PTSD is the
      only disorder in psychiatry in which the initiating factor, the trauma exposure,
      can be identified. Thus, the pathophysiology of the fear and stress response
      underlying PTSD can be examined and potentially interrupted. Twin studies have
      shown that the development of PTSD following a trauma is heritable, and that
      genetic risk factors may account for up to 30-40% of this heritability. A current
      goal is to understand the gene pathways that are associated with PTSD, and how
      those genes act on the fear/stress circuitry to mediate risk vs. resilience for
      PTSD. This review will examine gene pathways that have recently been analysed,
      primarily through candidate gene studies (including neuroimaging studies of
      candidate genes), in addition to genome-wide associations and the epigenetic
      regulation of PTSD. Future and on-going studies are utilizing larger and
      collaborative cohorts to identify novel gene candidates through genome-wide
      association and other powerful genomic approaches. Identification of PTSD
      biological pathways strengthens the hope of progress in the mechanistic
      understanding of a model psychiatric disorder and allows for the development of
      targeted treatments and interventions. 

PMID- 24103159
TI  - Patterns of engagement with the health care system and risk of subsequent
      hospitalization amongst patients with diabetes.
AB  - BACKGROUND: Re-hospitalization is common among patients with diabetes, and may be
      related to aspects of health care use. We sought to determine the association
      between patterns of health care engagement and risk of subsequent hospitalization
      within one year of discharge for patients with diabetes. METHODS: We identified
      adults with incident diabetes in Alberta, Canada, who had at least one
      hospitalization following their diabetes diagnosis between January 1, 2004 and
      March 31, 2011. We used Cox regression to estimate the association between
      factors related to health care engagement (prior emergency department use,
      primary care visits, and discharge disposition (i.e. whether the patient left
      against medical advice)) and the risk of subsequent all-cause hospitalization
      within one year. RESULTS: Of the 33,811 adults with diabetes and at least one
      hospitalization, 11,095 (32.8%) experienced a subsequent all-cause
      hospitalization within a mean (standard deviation) follow-up time of 0.68 (0.3)
      years. Compared to patients with no emergency department visits, there was a 4
      percent increased risk of a subsequent hospitalization for every emergency
      department visit occurring prior to the index hospitalization (adjusted Hazard
      Ratio [HR]: 1.04; 95% CI: 1.03-1.05). Limited and increased use of primary care
      was also associated with increased risk of a subsequent hospitalization. Compared
      to patients with 1-4 visits, patients with no visits to a primary care physician
      (adjusted HR: 1.11; 95% CI: 0.99-1.25) and those with 5-9 visits (adjusted HR:
      1.06; 95% CI: 1.00-1.12) were more likely to experience a subsequent
      hospitalization. Finally, compared to patients discharged home, those leaving
      against medical advice were more likely to have a subsequent hospitalization
      (adjusted HR: 1.74; 95% CI: 1.50-2.02) and almost 3 times more likely to have a
      diabetes-specific subsequent event (adjusted HR: 2.86; 95% CI: 1.82-4.49).
      CONCLUSIONS: Patterns of health care use and the circumstances surrounding
      hospital discharge are associated with an increased risk of subsequent
      hospitalization among patients with diabetes. Whether these patterns are related
      to the health care systems ability to manage complex patients within a primary
      care setting, or to access to primary care services, remains to be determined.

PMID- 24103160
TI  - The aluminium content of infant formulas remains too high.
AB  - BACKGROUND: Recent research published in this journal highlighted the issue of
      the high content of aluminium in infant formulas. The expectation was that the
      findings would serve as a catalyst for manufacturers to address a significant
      problem of these, often necessary, components of infant nutrition. It is
      critically important that parents and other users have confidence in the safety
      of infant formulas and that they have reliable information to use in choosing a
      product with a lower content of aluminium. Herein, we have significantly extended
      the scope of the previous research and the aluminium content of 30 of the most
      widely available and often used infant formulas has been measured. METHODS: Both
      ready-to-drink milks and milk powders were subjected to microwave digestion in
      the presence of 15.8 M HNO3 and 30% w/v H2O2 and the aluminium content of the
      digests was measured by TH GFAAS. RESULTS: Both ready-to-drink milks and milk
      powders were contaminated with aluminium. The concentration of aluminium across
      all milk products ranged from ca 100 to 430 MUg/L. The concentration of aluminium
      in two soya-based milk products was 656 and 756 MUg/L. The intake of aluminium
      from non-soya-based infant formulas varied from ca 100 to 300 MUg per day. For
      soya-based milks it could be as high as 700 MUg per day. CONCLUSIONS: All 30
      infant formulas were contaminated with aluminium. There was no clear evidence
      that subsequent to the problem of aluminium being highlighted in a previous
      publication in this journal that contamination had been addressed and reduced. It
      is the opinion of the authors that regulatory and other non-voluntary methods are
      now required to reduce the aluminium content of infant formulas and thereby
      protect infants from chronic exposure to dietary aluminium.

PMID- 24103161
TI  - The influences of maternal and neonatal factors on umbilical cord blood quality.

PMID- 24103162
TI  - Direct DNA and PNA probe binding to telomeric regions without classical in situ
      hybridization.
AB  - BACKGROUND: Fluorescence in situ Hybridization (FISH) utilizes peptide nucleic
      acid (PNA) probes to identify specific DNA sequences. Traditional techniques have
      required the heat denaturing of the DNA in formamide followed by multiple hours
      at moderated temperatures to allow the probe to hybridize to its specific target.
      Over the past 30 years, advancements in both protocols and probes have made FISH
      a more reliable technique for both biological research and medical diagnostics,
      additionally the protocol has been shortened to several minutes. These PNA probes
      were designed to target and hybridize to both DNA and RNA, and PNA-protein
      interactions still remain unclear. RESULTS: In this study we have shown that a
      telomeric single stranded specific PNA probe is able to bind to its target
      without heat denaturing of the DNA and without formamide. We have also identified
      a centromere specific probe, which was found to bind its target with only
      incubation with formamide. CONCLUSIONS: Certain PNA probes are able to hybridize
      with their targets with minimal to no denaturing of the DNA itself. This limited
      denaturing preserves the chromosome structure and may lead to more effective and
      specific staining.

PMID- 24103163
TI  - [Laryngopharyngeal reflux disease: questions, controversies and standardization].

PMID- 24103164
TI  - [Surface electromyographic study on swallowing in normal adults].
AB  - OBJECTIVE: To study the characteristics of surface electromyography (sEMG) during
      swallowing in normal adults. METHODS: The sEMG during swallowing was carried out
      in 126 normal adults. There were 66 males and 60 females with their age ranged
      from 18 to 65 years. The recording electrodes were placed on the skin above the
      superior thyroid notch and the duration and amplitude of muscle activities during
      every deglutition were recorded. Swallowing styles were dry swallow, 20 ml water
      swallow and 40 ml water swallow. RESULTS: The durations of sEMG at dry swallow,
      20 ml water swallow and 40 ml water swallow were (1.133 +/- 0.209)s (x- +/- s),
      (1.097 +/- 0.208)s, and (1.510 +/- 0.432)s, while the amplitudes were (0.332 +/-
      0.115)mV, (0.308 +/- 0.095)mV, and (0.399 +/- 0.139)mV in normal male group. The
      durations of sEMG at dry swallow, 20 ml water swallow and 40 ml water swallow
      were (1.118 +/- 0.170)s, (1.085 +/- 0.209)s, and (1.765 +/- 0.463)s, while the
      amplitudes were (0.292 +/- 0.100)mV, (0.261 +/- 0.113)mV, and (0.342 +/- 0.129)mV
      in normal female group. The amplitudes of sEMG in male were higher than those in
      female (P < 0.05) and the durations had no statistically significant difference
      between male and female (P > 0.05) in all swallow styles except that the duration
      of 40 ml water swallow in female was longer than that in male (P < 0.05). In all
      volunteers, the durations of sEMG at 40 ml water swallow were longer than those
      at dry swallow and 20 ml water swallow, and there was no statistically
      significant difference between dry swallow and 20 ml water swallow. The amplitude
      of sEMG at 40 ml water swallow was higher than that at dry swallow. The amplitude
      of sEMG in dry swallow was higher than that at 20 ml water swallow. There was no
      statistically significant difference in durations and amplitudes of sEMG among
      four different age groups of male. In the female groups, there was no
      statistically significant difference in durations and amplitudes of sEMG among
      four different age groups except that the duration at 40 ml water swallow was
      longer in younger group (<30 years old) than in older groups. CONCLUSIONS:
      Surface EMG of swallowing is a simple and noninvasive method for evaluating the
      swallowing function. The sEMG data of swallowing in normal adults obtained in
      this study may be used to provide reference for screening swallowing function in
      adults in the future.

PMID- 24103165
TI  - [Modified closed reduction for the arytenoid cartilage dislocation].
AB  - OBJECTIVE: To investigate the clinical characteristics of arytenoid cartilage
      dislocation and the outcome of modified closed reduction. METHODS: Sixty-seven
      patients with vocal fold immobility underwent modified closed reduction under
      local anesthesia through indirect laryngoscope. During reduction, a right-angled
      laryngeal forceps was used to hold the superior surface of the affected
      arytenoids and rotate in posterolateral or anteromedial direction according
      different situation of dislocation. Fifty-seven patients had previously undergone
      endotracheal intubation for surgery and 10 patients had nonintubated injury with
      blunt laryngeal trauma in 6 cases. Clinical characteristics, voice function,
      procedural skill and therapy outcome of those cases were evaluated. RESULTS: All
      patients complained of persistent hoarseness. Stroboscopy revealed vocal fold
      immobility (50 of 67 cases on the left side, 74.6%) and incomplete glottal
      closure with anterior arytenoid dislocations in 63 cases and posterior
      dislocations in 4 cases. The laryngeal electromyography (LEMG) results for 10 of
      38 patients (26.3%) of postintubation arytenoids dislocation displayed abnormal
      patterns with denervated potentials. The voice of all patients for postintubation
      arytenoids dislocation improved after modified closed reduction with normal in 51
      cases and slight hoarseness in 6 cases. The movement of the affected vocal folds
      recovered to normal in 54 cases and improved in 3 cases. Among the 10 patients
      with nonintubated vocal fold immobility, the voice and the movement of vocal
      folds were normal in 7 cases, improved in 1 case and no effective in 2 cases.
      CONCLUSIONS: Some cases of arytenoid dislocation were accompanied by an recurrent
      laryngeal nerve abnormality (mostly temporary and resolved after a reduction).
      The modified reduction technique under local anesthesia can restore patients'
      voice and vocal fold mobility within 6 weeks after dislocation. Nevertheless, the
      causes of vocal fold immobility following blunt laryngeal trauma were
      complicated, so the curative effect of arytenoids reduction in those cases may be
      limited by cicatricial contracture of laryngeal injured tissue.

PMID- 24103166
TI  - [Esophageal dynamic and laryngopharyngeal reflux play a role in pathogenesis of
      vocal cord polyps].
AB  - OBJECTIVE: Through monitoring esophageal dynamic change, and detection of
      laryngopharyngeal reflux(LPR) and gastroesophageal reflux events,to discuss the
      relationship of vocal cord polyps with laryngopharyngeal reflux. METHODS: Thirty
      two patients with vocal cord polyps were diagnosed by electronic laryngoscopy in
      Nanfang Hospital between October 2011 to May 2012. This study applied high
      resolution esophageal manometry (HRM) and ambulatory 24-hour multichannel
      intraluminal impedance-pH monitoring (MII-pH) to obtain the upper esophageal
      sphincter(UES) and lower esophageal sphincter pressure, characteristics of
      sectional esophageal motility; laryngopharyngeal reflux (LPR)and gastroesophageal
      reflux events, as well as the reflux properties of substances. Sixteen healthy
      volunteers were recruited as normal controls. RESULTS: UES relaxation duration,
      duration of UES relaxation time, UES relaxation recovery time and mean length of
      LES were all shorter than those of the control group (t were 2.244, 2.624, 2.310
      and -2.397, P < 0.05). There were 40.6% (13/32) LPR and 50.0% (16/32)
      gastroesophageal reflux found in vocal polyp patients. Median number (M [P25;
      P75]) of laryngopharyngeal acid reflux events were 0.5[0.0;3.5] and 0.0[0.0;0.0]
      in vocal polyp group and the controls, median mean time of laryngopharyngeal acid
      exposure 0.1[0.0;1.7] and 0.0[0.0;0.0] min, median clearance time of
      laryngopharyngeal acid were 3.5[0.0;53.5] and 0.0[0.0;0.0] s, median scores of
      DeMeester were 14.8[1.6;31.3] and 1.8[1.1;4.1] and median frequency of total
      liquid reflux episodes were 46.5[25.3;69.0] and 32.5[20.0;36.3], respectively.
      The median numbers of laryngopharyngeal acid reflux events, time of acid
      exposure, time of acid clearance, DeMeester scores and frequency of total liquid
      reflux episodes were increased or higher in vocal polyp group than those in the
      controls (z were 2.481, 2.767, 2.767, 2.344 and 1.980, P < 0.05). CONCLUSIONS:
      There are upper esophageal sphincter and Lower esophageal sphincter dismotility
      in vocal polyp patients with LPR. LPR events were dominated by acid reflux in
      upright position.Esophageal dynamic disfunction and LPR should be considered in
      the study of the pathogenesis of vocal cords polyps.

PMID- 24103167
TI  - [Study on the consistency of reflux score evaluated by three different level of
      throat physicians].
AB  - OBJECTIVE: The consistency of reflux finding score (RFS) was studied by three
      different level of throat physicians. METHODS: One hundred and ten laryngeal
      photos were chosen to assess the RFS test-retest reliability on two separate
      occasions at least more than one week. RESULTS: The mean total RFS scores for
      doctor A were 9.05 +/- 2.54, doctor B were 8.80 +/- 2.20, doctor C were 8.98 +/-
      2.21 at the initial screening, and 9.20 +/- 2.47, 9.03 +/- 2.14 and 8.91 +/- 2.30
      respectively at the repeat evaluation. The test-retest reliability of total RFS
      scores of three doctors were 0.860, 0.800 and 0.837 respectively, P all <0.001.
      The test-retest reliability of each item scores for doctor A were from 0.662 to
      1.000, doctor B were from 0.486 to 1.000 and doctor C were from 0.613 to 1.000.
      There were no differences in the total RFS scores comparing among each evaluation
      of the three doctors (chi(2) = 1.553, P = 0.907). Total RFS scores more than 7
      were considered as abnormal. The interobsever consistency was as follows: A with
      B was 83.6% (kappa = 0.617, P = 0.000), A with C was 85.5% (kappa = 0.644, P =
      0.000),B with C was 89.1% (kappa = 0.720, P = 0.000). The intraobserver
      consistency was 91.8% (kappa = 0.807, P = 0.000), 81.8% (kappa = 0.534, P =
      0.000), 90.9% (kappa = 0.741, P = 0.000) respectively. CONCLUSIONS: The result of
      this study shows that the assessment of RFS is not influenced by different
      educational backgrounds and clinical experience.RFS can be applied widely in
      China.

PMID- 24103168
TI  - [Application research on RBH perceptual evaluation of voice disorders].
AB  - OBJECTIVE: To investigate the reliability of RBH perceptual evaluation system,
      and the correlation between its perceptual and acoustic parameters inorder to
      providing the evidence for clinic practice. METHODS: The voice samples were
      collected from 100 patients with variable dysphonia and 15 normal people.
      According to the R, B, H parameters of the RBH system,voice samples were rated on
      4-point scale from 0 to 3. The interrater agreement and intrarater reliability
      were tested. The differences of the acoustic parameters between adjacent ranks in
      the perceptual parameters were investigated. The correlation between perceptual
      parameters and acoustic parameters were also studied. RESULTS: The interrater
      agreement and intrarater reliability were good. Intrarater reliability was
      varying from 0.428 to 0.608 using Kappa coefficient; intraclass correlation
      coefficients for interrater agreement were 0.741-0.797 and 0.689-0.762 in the
      twice perceptual assessments. The differences of the acoustic parameters between
      adjacent ranks in the perceptual parameters (R, B, H) were significant (P <
      0.05). The perceptual parameters (R, B, H) were significantly correlated with the
      acoustic parameters (Jitter, Shimmer, HNR, MPT and DSI, with r varying from 0.360
      to 0.551 or from -0.472 to -0.620, P < 0.01). CONCLUSION: The reliability of RBH
      perceptual evaluation system is good; its 4-point scale is acceptable; the
      perceptual parameters are correlated with the acoustic parameters; the RBH system
      has broad prospects in clinic practice.

PMID- 24103169
TI  - [Influence of the quantified surface electromyography of sternocleidomastoid on
      cervical vestibular evoked myogenic potential].
AB  - OBJECTIVE: This study investigated the correlations between electromyography
      (EMG) of sternocleidomastoid (SCM) and cervical vestibular evoked myogenic
      potentials (cVEMP), and intended to quantify the influence of EMG of SCM on cVEMP
      by recording the EMG of SCM and cVEMP in different head positions. METHODS:
      Thirty healthy subjects (60 ears), without the history of ear illnesses, were
      enrolled in this study. In addition, the recruited subjects also showed favorable
      differentiation of cVEMP waves induced by Blackman pip cVEMP, and EMG were
      recorded in different head positions(with sagittal at 90 degrees , 60 degrees ,45
      degrees  and 30 degrees angle), as well as to analyze and quantify the influence
      of EMG on cVEMP. RESULTS: In the case of the different EMG levels: P1 latency,
      (12.50 +/- 2.39)ms; N1 latency, (19.79 +/- 3.16)ms, and the latencies shown no
      statistical difference (P > 0.05). The amplitude was affected by EMG level, there
      was significant difference between the amplitudes(F = 55.47, P < 0.01). The
      different head positions on subjects their EMG level or area of EMG effects were
      statistically significant (P < 0.01). The study found a linear dependence of the
      amplitude from the EMG levels(r(2) = 0.591, Adjusted-r(2) = 9.590). CONCLUSIONS:
      The cVEMP amplitude increases as a function of EMG target level, and the latency
      remains constant. The quantized data will increase the amplitude in clinical
      diagnosis application of sensitivity, and it will improve the diagnosis of the
      vestibular system diseases and some related diseases.

PMID- 24103170
TI  - [CO2 laser supraglottoplasty for infantile laryngomalacia].
AB  - OBJECTIVE: To evaluate the feasibility and safety of CO2 laser supraglottoplasty
      for severe laryngomalacia in infants. METHODS: From January 2009 to December
      2011, 32 infants with severe laryngomalacia were confirmed by electronic
      laryngoscope and clinical assessment in Shenzhen Children's Hospital. According
      to the choice made by the parents, 16 children accepted CO2 laser
      supraglottoplasty (group 1), the others were treated conservatively (group 2).
      The beginning observation point T0 was defined as the age on the first medicine
      taking day or the age of surgery. T1, T3, T6 were defined as 1, 3, 6 months
      following T0. Clinical symptoms included stridor, dyspnea, aspiration, and
      respiratory infections. The body weight, PSG reports, laryngoscope findings, cure
      rates of the two groups were compared. RESULTS: The anatomical abnormalities were
      corrected surgically, and the symptoms ,such as stridor, dyspnea, and aspiration
      improved rapidly after the operation. The cure rates was higher in group 1 than
      in group 2 on T1, T3, T6 stage. There were statistically significant
      differences(chi(2) were 13.9, 28.1, 24.6 respectively; all P < 0.01). Children in
      group 1 gained weight better than in group 2. There was a statistically
      significant difference in Z scores median on T1, T3, T6 stage (z score were 
      0.848, -2.940, -4.110; P < 0.05, or P < 0.01 respectively). The lowest oxygen
      saturation in group 1 improved one month after the surgery (from average 0.686 +/
      0.106 to 0.901 +/- 0.041). There was a statistically significant difference (t =
      -7.876, P = 0.001). Complications included adhesion (1 case) and temporary new
      onset aspiration (1 case). CONCLUSIONS: The CO2 laser supraglottoplasty can
      resolve severe laryngomalacia symptoms including stridor, dyspnea and aspiration.
      It can reduce the frequency of respiratory infections, and contribute to weight
      gaining. The CO2 laser supraglottoplasty is effective, of high security and with
      rare complications.

PMID- 24103171
TI  - [Ultrastructure of the upper airway skeletal muscle in patients with obstructive
      sleep apnea hypopnea syndrome patients].
AB  - OBJECTIVE: To observe the ultrastructure of the upper airway skeletal muscle from
      patients with obstructive sleep apnea hypopnea syndrome (OSAHS) . METHODS:
      Sixteen OSAHS patients were recruited during Oct 2010 to Oct 2011. Ten patients
      with chronic tonsillitis were recruited as the control. Body mass index (BMI) was
      above 25 kg/m(2) in all patients. The upper air way skeletal muscle cells were
      observed by a transmission electron microscope .The relation between the
      ultrastructure and apnea hypopnea index (AHI), the lowest saturation of blood
      oxygen (LSaO2) was detected by statistic analysis. RESULTS: AHI and LSaO2 in
      OSAHS patients were (53.6 +/- 4.6)/h, and 0.754 +/- 0.023 while that of the
      control group were (2.27 +/- 1.1)/h and 0.968 +/- 0.014, which had statistically
      significant difference (t = 8.84, t = 6.90, P < 0.01). In OSAHS patients,
      electron microscope showed that muscle fibers can not be identified with
      disordered arrangement of structure, some of mitochondria were severe swollen and
      disrupted, a lot of liposome was observed. In the control group, muscle fibers
      were identified with well arrangement, also there were some mitochondria swollen,
      but no liposome was found. The amount of liposome in upper airway skeletal muscle
      in OSAHS patients was analyzed with shape counting scale, it was found that it
      had positive correlation with AHI (r(2) = 0.761, P < 0.01) but no correlation
      with BMI and LSaO2 (P > 0.05). CONCLUSION: Fatty change is the characteristic
      change of the upper airway skeletal muscle in OSAHS patients which was caused by
      hypoxia and vibration.

PMID- 24103172
TI  - [Nearby perforator flaps as alternative choices for anterolateral thigh flap when
      lacking useful perforator].
AB  - OBJECTIVE: To explore the proposal using nearby perforator flaps as alternative
      reconstructive choices for anterolateral thigh (ALT) flap when lacking useful
      perforator. METHODS: From August 2010 to August 2012, 8 cases with head and neck
      cancer were found lacking reliable perforator during ALT flap elevation, a tensor
      fascia latae (TFL) flap or an anteromedial thigh (AMT) flap was used to complete
      the reconstruction. RESULTS: All 8 alternative flaps were successfully harvested,
      other donor sites were not needed. Flap harvest time was 50-85 min. Of 5 TFL
      flaps, pedicle lengths were 6-10 cm, and the diameters of the arteries and veins
      were 2.5-3.0 mm and 2.5-3.5 mm respectively. Of 3 AMT flaps, pedicle lengths were
      10-15 cm, the rectus femoris branch was used as pedicle in 1 flap, with artery
      and vein more than 1.0 mm in diameter, and the descending branch of the lateral
      circumflex femoral artery was used as pedicle in other 2 flaps, the diameters of
      the arteries were 3.5 and 3.0 mm respectively, the diameters of the veins were
      3.5 mm. The donor sites were directly closed in 7 cases and skin graft was
      performed in another case. All the flaps were alive and no complication was found
      in the donor sites. CONCLUSION: TFL or AMT flap is an good alternative to ALT
      flap lacking useful perforator.

PMID- 24103173
TI  - [Transoral CO2 laser epiglottectomy for early epiglottic carcinomas].
AB  - OBJECTIVE: To compare the functional results of transoral CO2 laser
      epiglottectomy with transcervical supraglottic laryngectomy and to find the
      landmarks for CO2 laser surgery. METHODS: Forty-nine preoperatively untreated
      patients diagnosed as clinical T1-2N0M0 epiglottic carcinomas enrolled from June
      1, 2006, to November 1, 2009 in the Second Affiliated Hospital of Harbin Medical
      University were studied retrospectively. Seventeen cases were treated by CO2
      laser whereas 32 by open surgeries. The upper edge of thyroid cartilage and
      mucosal recess infra epiglottic tubercle could be used as intraoperation
      landmarks for transoral CO2 laser surgery. Optional neck dissections (II, III)
      were performed for 34 patients with tumors on laryngeal face, but not for 15 with
      tumors on the edges of epiglottis or small laryngeal face tumors. RESULTS: The
      follow-up for this study covers a period ranging from 3 to 6 years
      postoperatively. Four local recurrences were found for this study, 2 for laser
      surgery who underwent additional repeated exisions and 2 for conventional
      techniques, one received radiotherapy (60 Gy) and another with total
      laryngectomy. The incidence of lymph node metastasis was 10.2% (5/49) in all
      cases. Time of naso-feeding or hospitalisation was significantly shorter for CO2
      laser treated patients than that for open techniques. Overall 3 year's survival
      rates were 100% and 90.6% for CO2 laser and the open techniques respectively.
      CONCLUSIONS: Compared to the open technique, transoral CO2 laser epiglottectomy
      is a well-tolerated and promising resection technique with low morbidity for
      early epiglottic carcinomas, and the identification of landmarks is useful for
      entire resection of epiglottis.

PMID- 24103174
TI  - [Logistic regression analysis of contrast-enhanced ultrasound and ultrasonic
      elastography in differential diagnosis of thyroid nodules].
AB  - OBJECTIVE: To evaluate the contrast-enhanced ultrasound(CEUS) and ultrasonic
      elastography (UE) in diagnosis of thyroid nodules by a binary Logistic regression
      model. METHODS: A total 149 cases with thyroid nodules were examed by CEUS and UE
      and were confirmed by surgical pathology. A Logistic model was obtained on the
      basis of ultrasonographic features. Receiver operator characteris(ROC) curve was
      constructed to assess the performance of the Logistic model. RESULTS: Four
      ultrasonographic features including calcification, enhancement degree, biggest
      perfusion strength and elastic score were finally entered into the Logistic
      model. The percentage of correct prediction was 91.90%. CONCLUSION: Both CEUS and
      UE have high value in differential diagnosis of thyroid nodules and the Logistic
      regression model has high diagnostic rate.

PMID- 24103175
TI  - [MicroRNAs regulate epithelial-mesenchymal transition of supraglottic laryngeal
      cancer].
AB  - OBJECTIVE: To study microRNAs (miRNAs) expression profiles associated with
      epithelial-mesenchymal transition (EMT) in lymph node metastasis of supraglottic
      laryngeal squamous cell carcinomas(SGLSCC). METHODS: Primary tumor tissue samples
      of 12 SGLSCC patients were collected, including 6 patients clinically diagnosed
      with lymph nodes metastasis (N(+)) and 6 patients with lymph nodes metastasis
      free (N0), for miRNA microarray gene-expression profiling to identify the
      differences between N(+) and N0 groups. Differentially expressed miRNAs was
      verified using quantitative real-time PCR in 20 patients with N(+) and 20
      patients with N0. Target genes for the miRNAs associated with EMT in SGLSCC
      metastasis were analyzed. RESULTS: Ten miRNAs differentially expressed between
      N(+) group and N0 group were determined. Comparing with N0 group, nine miRNAs
      were over-expressed and one miRNA was expressed at lower level in N(+) group. The
      genes for miR-192, miR-143, miR-409 and miR-634 were predicted as target genes
      that could promote EMT of laryngeal cancer cells by targeted inhibiting Kruppel
      like factor 17(KLF17), E-cadherin and phosphatidylinositol 3 kinase (PI3K).
      CONCLUSIONS: The miRNAs over-expressed in group N(+) can be used to predict
      cervical lymph node metastasis in SGLSCC. The miRNAs as new markers could improve
      the diagnosis and treatment of SGLSCC.

PMID- 24103177
TI  - [Relationship between children's obstructive sleep apnea hypopnea syndrome and
      nasal diseases].
AB  - OBJECTIVE: To explore the relationship between children obstructive sleep apnea
      hypopnea syndrome (OSAHS) and nasal diseases. METHODS: Three hundred and thirty
      eight cases of pediatric OSAHS confirmed by polysomnography (PSG) had been
      enrolled as the treatment group, and divided into mild subgroup, moderate
      subgroup and severe subgroup according to the obstructive apnea index (OAI) and
      apnea hypoventilation index (AHI). The other two hundred and seven pediatric
      vocal cord nodule cases without OSAHS had been randomly selected as the control
      group. The retrospective analysis of upper respiratory tract infection frequency
      per year, expression levels of total IgE (tIgE) and allergen-specific IgE (sIgE),
      results of electronic nasopharyngoscope test and nasal sinus CT scans had been
      performed in all the pediatric cases. The data were analyzed by SPSS 17.0.
      RESULTS: The upper respiratory tract infection frequency per year, ratio of cases
      with positive results of tIgE, ratio of cases with nasosinusitis, ratio of cases
      with narrow nasal cavity in the experiment group were respectively 8.7 +/- 5.7,
      60.9%, 79.9% and 50.0%, while those in the control group were respectively 4.4 +/
      2.6, 32.8%, 12.1% and 6.3%, with significant difference between groups (t =
      7.578,chi(2) value was 41.943, 237.704, 110.322, all P < 0.01). The multiple
      regression analysis indicated that, nasosinusitis and narrow nasal cavity were
      the two major risk factors of pediatric OSAHS (OR1 = 16.008, OR2 = 4.671, all P <
      0.01), with combined effects (OR = 113.430, P < 0.01) . The rank test analysis in
      term of risk factors of severity of OSAHS had indicated that, prevalence of
      nasosinusitis and narrow nasal cavity were increased as rising severity of OSAHS
      (chi1(2) = 21.571, chi2(2) = 17.304, all P < 0.01). CONCLUSIONS: Infection and
      allergy are risk factors of pediatric OSAHS. Nasosinusitis and narrow nasal
      cavity are two major risk factors of pediatric OSAHS, which have positive
      relationship with the severity of OSAHS.

PMID- 24103176
TI  - [Analysis of allergen variation for 3292 patients with allergic rhinitis].
AB  - OBJECTIVE: To investigate the variation of common allergens in patients with
      allergic rhinitis in recent 4 years in Tianjin First Center Hospital. METHODS:
      The medical records of skin prick test on 3292 patients with allergic rhinitis
      between 2009 and 2012 were restrospectively analyzed. The changing trend of
      various allergens in 4 years and distribution differences were compared. The
      differences of the top 5 allergens in under age group, adult group and different
      gender group were further analyzed by SPSS 19.0 software. RESULTS: The positive
      rate of dermatophagoides farinae was increasing year by year, from 45.1% in 2009
      to 66.3% in 2012, and the positive rate of dermatophagoides pteronyssinus
      increased from 42.0% in 2009 to 58.6% in 2012, the difference was statistically
      significant (chi(2) value was 68.70, 41.55, all P < 0.01). The positive rate of
      dermatophagoides farinae and dermatophagoides pteronyssinus in adult group and
      male group showed significant upward trend year by year (chi(2) value was 75.85,
      69.93, 274.25, 42.62, all P < 0.01), but not in adult group and female group. The
      positive rate of quinoa, mugwort and humulus scandens decreased year by year
      between 2009 and 2011(chi(2) value was 22.08, 11.64, 203.19, all P < 0.01), but
      increased again in 2012(chi(2) value was 21.55, 29.38, 12.40, all P < 0.01).
      CONCLUSIONS: There is a tendency of change of allergens in patients with AR. This
      phenominon may be helpful for doctors to choose the type of skin prick liquid.

PMID- 24103178
TI  - [Logistic regression analysis on influence factors of chronic sinusitis after
      endoscopic sinus surgery].
AB  - OBJECTIVE: To explore the clinical effect and the influence factors after
      endoscopic surgery for chronic sinusitis. METHODS: The clinical data of 337
      patients with chronic sinusitis treated by endoscopic surgery were analyzed,
      including gender, age, culture level, course of the disease, the days of
      hospitalization, medical history, smoking, drinking, early surgery history,
      allergic rhinitis (AR) history, clinical classification, visual analogue scale
      (VAS) score, nasal endoscopy score, nasal polyps, CT examination score, side,
      nasal adhesion and postoperative follow-up compliance. The clinical effect of
      endoscopic sinus surgery was evaluated 6 months after operation according to the
      1997 Haikou standard. SPSS 18.0 software and conducted chi-square test and
      logistic regression analysis were used to analyze the data. RESULTS: Three
      hundred and thirty-seven chronic sinusitis patients were followed up after
      endoscopic surgery. It was found that 298 cases (88.4%) cured, 29 cases (8.6%)
      improved, 10 cases (3.0%) invalid. The clinical curative effect of the patients
      with chronic rhinosinusitis without nasal polyp was better than that of the
      patients with chronic rhinosinusitis with nasal polyp, the difference was
      statistically significant (chi(2) = 10.932, P < 0.01). After many factors
      Logistic regression analysis, the most important effect factor in the clinical
      curative effect were clinical type, AR or not, VAS score, nasal endoscopic
      examination score, CT examination score, multiple nasal polyp or not,
      postoperative nasal adhesion or not and postoperative follow-up compliance.
      CONCLUSION: The clinical effective of endoscopic sinus surgery is influenced by
      not only surgery itself, but also by clinical classification, whether and not
      with AR and so on.

PMID- 24103179
TI  - [Repairment of spontaneous cerebrospinal fluid otorrhea through middle fossa
      craniotomy and mastoid approach in two cases].

PMID- 24103180
TI  - [One case of cerebrospinal fluid rhinorrhea repairment with postoperative brain].

PMID- 24103181
TI  - [Report of 4 cases with trichofolliculoma].

PMID- 24103182
TI  - [Diagnosis and treatment of unusually located paragangliomas in head and neck: a
      report of 2 cases].

PMID- 24103183
TI  - [Advances in reasearch on congenital preauricular fistula].

PMID- 24103184
TI  - [Vocal dysphonia feature caused by the central diseases].

PMID- 24103185
TI  - [American head and neck surgery progress of in 2012].

PMID- 24103186
TI  - Thiol-blocking electrophiles interfere with labeling and detection of protein
      sulfenic acids.
AB  - Cellular exposure to reactive oxygen species induces rapid oxidation of DNA,
      proteins, lipids and other biomolecules. At the proteome level, cysteine thiol
      oxidation is a prominent post-translational process that is implicated in normal
      physiology and numerous pathologies. Methods for investigating protein oxidation
      include direct labeling with selective chemical probes and indirect tag-switch
      techniques. Common to both approaches is chemical blocking of free thiols using
      reactive electrophiles to prevent post-lysis oxidation or other thiol-mediated
      cross-reactions. These reagents are used in large excess, and their reactivity
      with cysteine sulfenic acid, a critical oxoform in numerous proteins, has not
      been investigated. Here we report the reactivity of three thiol-blocking
      electrophiles, iodoacetamide, N-ethylmaleimide and methyl methanethiosulfonate,
      with protein sulfenic acid and dimedone, the structural core of many sulfenic
      acid probes. We demonstrate that covalent cysteine -SOR (product) species are
      partially or fully susceptible to reduction by dithiothreitol, tris(2
      carboxyethyl)phosphine and ascorbate, regenerating protein thiols, or, in the
      case of ascorbate, more highly oxidized species. The implications of this
      reactivity on detection methods for protein sulfenic acids and S-nitrosothiols
      are discussed. 

PMID- 24103187
TI  - Neural correlates of rapid antidepressant response to ketamine in bipolar
      disorder.
AB  - OBJECTIVES: Ketamine, an N-methyl d-aspartate (NMDA) antagonist, has rapid
      antidepressant effects in depressed subjects with bipolar disorder (BD). Evidence
      supports a role for the glutamatergic system in the pathophysiology of BD. This
      double-blind, randomized, cross-over study sought to determine cerebral metabolic
      correlates of antidepressant response to ketamine. METHODS: Twenty-one subjects
      with BD currently in a depressed state underwent [(18) F]-fluorodeoxyglucose
      (FDG) positron emission tomography (PET) imaging after receiving a placebo
      infusion as well as after receiving a ketamine infusion. Metabolism was compared
      between ketamine and placebo infusions, and correlated with clinical response.
      Regional metabolic rate of glucose (rMRGlu) in regions of interest (ROIs) and
      Montgomery-Asberg Depression Rating Scale (MADRS) scores were the main outcome
      measures. RESULTS: The study found that change in metabolism between sessions was
      significantly correlated with percentage change in MADRS scores in the right
      ventral striatum; subjects who showed the greatest improvement had the largest
      metabolic increase after ketamine infusion compared to placebo. In a voxel-wise
      analysis, subjects with BD had significantly lower glucose metabolism in the left
      hippocampus following the ketamine infusion than following the placebo infusion.
      In addition, metabolism in the subgenual anterior cingulate cortex (ACC)
      following the placebo infusion was positively correlated with percentage
      improvement in MADRS score following the ketamine infusion. CONCLUSIONS: Taken
      together, the results suggest that higher activity in the subgenual ACC may
      predict antidepressant response to ketamine. Ketamine administration altered
      glucose metabolism in areas known to be involved in mood disorders; these
      alterations may partially underlie ketamine's mechanism of action.

PMID- 24103188
TI  - Short-term, daily intake of yogurt containing Bifidobacterium animalis ssp.
      lactis Bf-6 (LMG 24384) does not affect colonic transit time in women.
AB  - The present study investigated the effect of Bifidobacterium animalis ssp. lactis
      Bf-6 (LMG 24 384) (Bf-6)-supplemented yogurt on colonic transit time (CTT). A
      triple-blinded, randomised, placebo-controlled, two-period cross-over trial was
      conducted with sixty-eight women with a self-reported history of straining during
      bowel movements or hard or lumpy stools in the past 2 years. As per regulatory
      requirements for probiotic studies, eligible women were generally healthy and not
      actively constipated at the time of enrolment. Participants consumed both Bf-6
      and placebo yogurts for 14 d each in a randomised order, with a 6-week washout
      period between the treatments. The primary outcome, CTT, was assessed via Sitz
      marker X-rays. The average CTT was 42.1 h for the active period and 43.3 h for
      the control period (mean difference 1.2 h, 95 % CI - 4.9, 7.4). Since the
      statistical tests for the cross-over study implied that the mean CTT for the
      active and control periods in period 2 were biased, the standard protocol
      suggests examining the results of only period 1 as a traditional randomised
      controlled trial. This showed that the mean CTT was 35.2 h for the active period
      v. 52.9 h for the control period (P= 0.015). Bootstrapping demonstrated that both
      the mean and median differences remained significant (P= 0.016 and P= 0.045,
      respectively). Few adverse events were noted, with no differences among the
      active and control periods. The paired analysis showed no differences between the
      active and control periods during the cross-over trial. Further trials should be
      conducted in populations with underlying problems associated with disordered
      transit to determine the potential value of probiotic supplementation more
      accurately. 

PMID- 24103189
TI  - Cardiovascular safety trials: be careful what you wish for.

PMID- 24103190
TI  - Comparison of non-directive counselling and cognitive behaviour therapy for
      patients presenting in general practice with an ICD-10 depressive episode: a
      randomized control trial.
AB  - BACKGROUND: Most evidence in the UK on the effectiveness of brief therapy for
      depression concerns cognitive behaviour therapy (CBT). In a trial published in
      2000, we showed that non-directive counselling and CBT were equally effective in
      general practice for patients with depression and mixed anxiety and depression.
      Our results were criticized for including patients not meeting diagnostic
      criteria for a depressive disorder. In this reanalysis we aimed to compare the
      effectiveness of the two therapies for patients with an ICD-10 depressive
      episode. METHOD: Patients with an ICD-10 depressive episode or mixed anxiety and
      depression were randomized to counselling, CBT or usual general practitioner (GP)
      care. Counsellors provided nondirective, interpersonal counselling following a
      manual that we developed based on the work of Carl Rogers. Cognitive behaviour
      therapists provided CBT also guided by a manual. Modelling was carried out using
      generalized estimating equations with the multiply imputed datasets. Outcomes
      were mean scores on the Beck Depression Inventory, Brief Symptom Inventory, and
      Social Adjustment Scale at 4 and 12 months. RESULTS: A total of 134 participants
      were randomized to CBT, 126 to counselling and 67 to usual GP care. We undertook
      (1) an interaction analysis using all 316 patients who were assigned a diagnosis
      and (2) a head-to-head comparison using only those 130 (41%) participants who had
      an ICD-10 depressive episode at baseline. CBT and counselling were both superior
      to GP care at 4 months but not at 12 months. There was no difference in the
      effectiveness of the two psychological therapies. CONCLUSIONS: We recommend that
      national clinical guidelines take our findings into consideration in recommending
      effective alternatives to CBT.

PMID- 24103191
TI  - Erectile dysfunction and sex hormone changes in chronic obstructive pulmonary
      disease patients.
AB  - BACKGROUND: The prevalence of sexual dysfunction in patients with COPD is high
      and its significance has not been sufficiently stressed. The aim of this study is
      to investigate the incidence of erectile dysfunction (ED) and the factors
      affecting its frequency in COPD patients. METHODS: Seventy patients with COPD and
      68 healthy volunteers were included in the study. The International Index of
      Erectile Function questionnaire was used to evaluate ED, and the Beck Depression
      Inventory was used to evaluate depression. RESULTS: The smoking rate was higher
      and oxygen saturation (SaO2) and body mass index (BMI) were lower in the COPD
      group. Blood tests revealed higher levels of follicle stimulating hormone (FSH),
      luteinizing hormone (LH), and estradiol. Testosterone level was lower but it was
      not statistically significant. Various degrees of ED were detected in 78.6% of
      COPD patients and 55.8% of the controls. Depression was more common in the COPD
      group. There was a negative correlation between forced expiratory volume in 1 sec
      (FEV1) level and ED and between SaO2 and ED in the COPD group. A positive
      correlation was noted between age and ED in both groups. No significant
      correlation was found among hormonal status and FEV1, ED, depression, SaO2, or
      BMI. CONCLUSIONS: The present study provides further confirmation that COPD is a
      risk factor for erectile dysfunction. When establishing a treatment plan for
      improving the pulmonary function of COPD patients, sexual dysfunction and
      depression, which are usually neglected but diminish quality of life, should also
      be addressed.

PMID- 24103192
TI  - Nickel-containing nano-sized islands grown on Ge(111)-c(2 * 8) and Ag/Ge(111)-(?3
      * ?3) surfaces.
AB  - The formation of nano-islands on both a Ge(111)-c(2 * 8) surface and an
      Ag/Ge(111)-(?3 * ?3) surface evaporated with 0.1 ML Ni was investigated by
      scanning tunneling microscopy (STM). We have noticed that at temperatures lower
      than 670 K, the reaction between Ni and the individual substrate surfaces
      proceeds to form different structures: flat-topped islands with a 2?7 * 2?7 or a
      3 * 3 reconstruction on the Ni/Ge(111)-c(2 * 8) surface vs. islands with a 7 * 7
      reconstruction on the Ni/Ag/Ge(111)-(?3 * ?3) surface. From this we have inferred
      that within a temperature range between room temperature and 670 K, the
      intermediate Ag layer retards mixing between Ni and Ge atoms. As a result, the
      grown islands are composed of pure Ni atoms. Within a temperature range from 670
      to 770 K, most islands produced on the Ag/Ge(111)-(?3 * ?3) surface are identical
      with those formed on the Ni/Ge(111)-c(2 * 8) surface, suggesting that above 670
      K, Ni atoms are likely to bind with Ge atoms. However, an essential difference
      between STM images of the surfaces under study exists in the appearance of large
      elongated islands on the Ni/Ag/Ge(111)-(?3 * ?3) surface. The formation of the
      latter is explained in terms of a difference in energy for Ni diffusion on the
      Ge(111)-c(2 * 8) and Ag/Ge(111)-(?3 * ?3) surfaces. 

PMID- 24103193
TI  - SNPs detection in DHPS-WDR83 overlapping genes mapping on porcine chromosome 2 in
      a QTL region for meat pH.
AB  - BACKGROUND: The pH is an important parameter influencing technological quality of
      pig meat, a trait affected by environmental and genetic factors. Several
      quantitative trait loci associated to meat pH are described on PigQTL database
      but only two genes influencing this parameter have been so far detected:
      Ryanodine receptor 1 and Protein kinase, AMP-activated, gamma 3 non-catalytic
      subunit. To search for genes influencing meat pH we analyzed genomic regions with
      quantitative effect on this trait in order to detect SNPs to use for an
      association study. RESULTS: The expressed sequences mapping on porcine
      chromosomes 1, 2, 3 in regions associated to pork pH were searched in silico to
      find SNPs. 356 out of 617 detected SNPs were used to genotype Italian Large White
      pigs and to perform an association analysis with meat pH values recorded in
      semimembranosus muscle at about 1 hour (pH1) and 24 hours (pHu) post mortem.The
      results of the analysis showed that 5 markers mapping on chromosomes 1 or 3 were
      associated with pH1 and 10 markers mapping on chromosomes 1 or 2 were associated
      with pHu. After False Discovery Rate correction only one SNP mapping on
      chromosome 2 was confirmed to be associated to pHu. This polymorphism was located
      in the 3'UTR of two partly overlapping genes, Deoxyhypusine synthase (DHPS) and
      WD repeat domain 83 (WDR83). The overlapping of the 3'UTRs allows the co
      regulation of mRNAs stability by a cis-natural antisense transcript method of
      regulation. DHPS catalyzes the first step in hypusine formation, a unique amino
      acid formed by the posttranslational modification of the protein eukaryotic
      translation initiation factor 5A in a specific lysine residue. WDR83 has an
      important role in the modulation of a cascade of genes involved in cellular
      hypoxia defense by intensifying the glycolytic pathway and, theoretically, the
      meat pH value. CONCLUSIONS: The involvement of the SNP detected in the DHPS/WDR83
      genes on meat pH phenotypic variability and their functional role are suggestive
      of molecular and biological processes related to glycolysis increase during post
      mortem phase. This finding, after validation, can be applied to identify new
      biomarkers to be used to improve pig meat quality.

PMID- 24103194
TI  - Stroke-induced opposite and age-dependent changes of vessel-associated markers in
      co-morbid transgenic mice with Alzheimer-like alterations.
AB  - The pathophysiological concept of ischaemic stroke was recently expanded to a
      more comprehensive perspective, focussing on the vasculature as well as peri- and
      juxtavascular cells including astrocytes. Increasing evidence also supports a
      role of the vasculature in Alzheimer's disease (AD), but causal relationships are
      poorly understood. The purpose of this study was to examine vascular alterations
      due to cerebral ischaemia in aged wildtype (WT) mice and in the triple-transgenic
      (3xTg) mouse model of AD. Three- and 12-month-old WT and 3xTg mice underwent
      permanent middle cerebral artery occlusion. One day after ischaemia onset,
      expression of collagen IV and laminin as basement membrane constituents, and
      Solanum tuberosum lectin (STL) as endothelial marker was quantified in the
      ischaemic neocortex, striatum and hippocampus. Further, CD31- and aquaporin-4
      immunoreactivity served for coverage of endothelium and astrocyte endfeet.
      Ischaemia resulted in strong upregulation of collagen IV and laminin in the
      neocortex of 3-month-old WT and 3xTg mice, while STL appeared unaffected.
      Quantification confirmed collagen IV upregulation in the ischaemic neocortex of 3
      and 12-month-old WT and 3xTg mice, whereas striatal changes were limited to
      young WT mice. However, collagen IV expression in the hippocampus appeared nearly
      unaltered. Qualitative and quantitative data evidenced more severe degeneration
      of endothelial cells and astrocyte endfeet in 3xTg mice. In conclusion, this
      study supports the critical impact of the vasculature in the aged and AD brain by
      showing an age- and genetic background-dependent response of basement membranes
      to cerebral ischaemia, and a pronounced endothelial and astrocytic degeneration
      in the AD-like brain. 

PMID- 24103195
TI  - Protein quality control in time and space - links to cellular aging.
AB  - The evolutionary theory of aging regards aging as an evolved characteristic of
      the soma, and proponents of the theory state that selection does not allow the
      evolution of aging in unicellular species lacking a soma-germ demarcation.
      However, the life history of some microorganisms, reproducing vegetatively by
      either budding or binary fission, has been demonstrated to encompass an ordered,
      polar-dependent, segregation of damage leading to an aging cell lineage within
      the clonal population. In the yeast Saccharomyces cerevisiae and the bacterium
      Escherichia coli, such segregation is under genetic control and includes an
      asymmetrical inheritance of protein aggregates and inclusions. Herein, the
      ultimate and proximate causation for such an asymmetrical inheritance, with
      special emphasis on damaged/aggregated proteins in budding yeast, is reviewed. 

PMID- 24103196
TI  - How do people with persecutory delusions evaluate threat in a controlled social
      environment? A qualitative study using virtual reality.
AB  - BACKGROUND: Environmental factors have been associated with psychosis but there
      is little qualitative research looking at how the ongoing interaction between
      individual and environment maintains psychotic symptoms. AIMS: The current study
      investigates how people with persecutory delusions interpret events in a virtual
      neutral social environment using qualitative methodology. METHOD: 20 participants
      with persecutory delusions and 20 controls entered a virtual underground train
      containing neutral characters. Under these circumstances, people with persecutory
      delusions reported similar levels of paranoia as non-clinical participants. The
      transcripts of a post-virtual reality interview of the first 10 participants in
      each group were analysed. RESULTS: Thematic analyses of interviews focusing on
      the decision making process associated with attributing intentions of computer
      generated characters revealed 11 themes grouped in 3 main categories (evidence in
      favour of paranoid appraisals, evidence against paranoid appraisals, other
      behaviour). CONCLUSIONS: People with current persecutory delusions are able to
      use a range of similar strategies to healthy volunteers when making judgements
      about potential threat in a neutral environment that does not elicit anxiety, but
      they are less likely than controls to engage in active hypothesis-testing and
      instead favour experiencing "affect" as evidence of persecutory intention.

PMID- 24103197
TI  - A retrospective study of antipsychotic drug switching in a pediatric population.
AB  - BACKGROUND: Antipsychotic drugs can be used to help treat a wide variety of
      psychiatric disorders. However, specific antipsychotic drugs for any particular
      patient may need to be changed for a number of different reasons, including a
      lack of therapeutic efficacy and / or intolerance to medication side-effects.
      Drug switching may occur through a limited number of established patterns. The
      nature of these changes is not well characterized in youth, despite their
      frequent occurrence. METHODS: A retrospective analysis of antipsychotic drug
      switches was conducted on patients who had been admitted as inpatients to a
      tertiary care child and adolescent psychiatric institute. PharmaNet (a large,
      central administrative database) records of all medications prescribed in the 52
      weeks prior to admission, and then between admission and discharge, were analyzed
      for switching patterns. Additional data regarding diagnoses were obtained from
      medical chart review. RESULTS: Patients represented a diagnostically
      heterogeneous population, and almost all antipsychotic drugs were administered
      off-label. In the one year prior to and during admission to the hospital, a total
      of 31 out of 139 patients switched antipsychotic drugs. The frequency of
      switching increased closer to the time of admission, and the proportional rate of
      switching was even higher during hospital stay. The most common switch was from
      risperidone to quetiapine. Our analysis identified three main patterns of drug
      switching, all occurring with similar frequency: titrated drug switches, abrupt
      drug switches and concurrent drug administration. CONCLUSIONS: The present study
      indicates that antipsychotic drug switching in youth may be relatively common,
      particularly in the year prior to hospitalization. No specific manner of drug
      switching predominates. This study also demonstrates the feasibility of using
      large administrative databases to characterise switching patterns in youth.

PMID- 24103198
TI  - Relationships between the intention to use guidelines, behaviour of insurance
      physicians and their determinants.
AB  - BACKGROUND: We studied the intention of a group of insurance physicians to use
      the guidelines for depression, and their behaviour in disability assessments. We
      considered attitude, social norm and self-efficacy, knowledge/skills and stimuli,
      based on the Attitude-Social norm-self-Efficacy model (ASE model) as possible
      determinants of both intention and behaviour.The aim of this study was to
      understand the determinants of insurance physicians' behaviour when they are
      expected to use guidelines in daily practice. METHOD: A representative sample of
      42 insurance physicians participated in this study. Cross-sectional data were
      collected by means of a questionnaire based on the ASE model. We developed the
      questionnaire on the basis of literature and ascertained the content validity of
      it. Behaviour was made to comprise both "use of the guidelines" and "change in
      disability assessment behaviour" by the insurance physicians. Reliability
      analyses were performed to form additive scales of the ASE constructs. These
      scales were analysed with structural equations modelling (LISREL), by modifying a
      start model into a final model with a good fit, within theoretical constraints.
      In these analyses special attention was paid to the fact that the sample size was
      small. RESULTS: The most important determinants of the intention and the self
      reported use of the guidelines, were: the influence of colleagues, the self
      efficacy of the insurance physicians in their use of the guidelines, and the way
      the guidelines were implemented. The intention to use the guidelines for
      depression was not associated with the self-reported use of these guidelines, but
      there proved to be a faint, positive association with the self-reported change in
      assessment behaviour. CONCLUSIONS: Almost all the insurance physicians in this
      study intended to use at least elements of the guidelines. Their intention, self
      reported use of the guidelines and self-reported change in assessment behaviour
      were explored with help of the ASE model. The model suggested relationships
      between intention, self reported use of the guidelines and self-reported change
      in assessment behaviour on the on the one hand and various determinants on the
      other hand. Be that as it may, we see opportunities to improve insurance
      physicians' guideline adherence by offering them a multifaceted training in which
      they learn to apply the guidelines for depression.

PMID- 24103199
TI  - Asparagus racemosus ameliorates cisplatin induced toxicities and augments its
      antileishmanial activity by immunomodulation in vivo.
AB  - Current drugs for the treatment of visceral leishmaniasis are inadequate and
      their efficacies are also compromised due to suppression of immune function
      associated during the course of infection. To overcome this problem, efforts are
      needed to develop therapies with effective immunomodulatory agents where decrease
      of parasitic burden and simultaneous enhancement of adaptive immunity can be
      achieved. In this study we have evaluated a new therapeutic approach based on
      combination of Asparagus racemosus, an immunomodulatory drug, in combination with
      cisplatin against Leishmania donovani infected BALB/c mice. We demonstrate that
      A. racemosus (650 mg/kg b.wt./day for 15 days, orally) in combination with
      cisplatin (5 mg/kg b.wt./day for 5 days, intraperitoneally) enhanced the
      clearance of parasites as determined by Giemsa-stained liver impression smears.
      Besides having better killing activity, this combination group achieved increased
      production of disease resolving Th-1 response (IFN-gamma, IL-2), heightened DTH
      (delayed type hypersensitivity) response and augmented levels of IgG2a. Moreover,
      A. racemosus in combination with cisplatin not only provided enhanced protective
      immune response but also resulted in remarkable improved kidney and liver
      function tests as manifested by normal levels of SGOT, SGPT, alkaline
      phosphatase, creatinine and urea in blood plasma with normal histological
      observations as compared to only cisplatin treated L. donovani infected BALB/c
      mice. Through this study we have ascertained that A. racemosus in combination
      with cisplatin in L. donovani infected BALB/c mice boosted as well as restored
      both cellular and humoral immunity. Thus in view of severe immunosuppression in
      visceral leishmaniasis, a better and effective strategy for optimum efficacy of
      future antileishmanial drugs would direct not only killing of parasite by the
      drug, but also simultaneous generation of immunity against the disease.

PMID- 24103201
TI  - [The evaluation of fluid resuscitation].

PMID- 24103200
TI  - A thioredoxin reductase and/or thioredoxin system-based mechanism for antioxidant
      effects of ambroxol.
AB  - Long-term treatment with ambroxol (ABX), a bronchial expectorant, was found to
      prevent acute exacerbation of chronic obstructive pulmonary disease (AECOPD). The
      underlying mechanism remains unclear. To address this, we have investigated the
      effect of ABX on critical antioxidant proteins thioredoxin (Trx) and thioredoxin
      reductase (TrxR) that are decreased in patients with AECOPD. Trx, TrxR and
      NADP(H) form Trx system, which is involved in regulating numerous oxidative
      stress-related events. In human bronchial epithelial cells, treatment with ABX
      from 0 to 200 MUM gradually increased mRNA and protein levels of TrxR/Trx. At
      these ABX concentrations, TrxR activity was elevated progressively, whereas Trx
      activity exhibited a dose-dependent biphasic response, increasing at 50 and 75
      MUM, but decreasing at ABX over 150 MUM. Pre-treatment with 75 MUM ABX enhanced
      the capacity of the cells to eliminate reactive oxygen species, which was largely
      prevented by knockdown of cytosolic Trx (hTrx1). In a purified system, ABX
      shortened the initial lag phase during the reduction of insulin disulfide by Trx
      system. Pre-treatment of NADPH-reduced TrxR with ABX caused a dose- and time
      dependent increase in thiolate/selenolate species, i.e. the catalytically active
      form of TrxR. Kinetic analysis demonstrated that the reduction of H2O2 by TrxR or
      Trx system were enhanced by 100 or 200 MUM ABX. When hTrx1 was mixed with ABX in
      a molar ratio of 1:1 to 1:100 (which could occur in human plasma), changes in
      intrinsic Trp fluorescence occurred, and the response of reduced hTrx1 was
      especially remarkable. These data reveal an ABX-sensing mechanism of TrxR/Trx. We
      therefore conclude that the antioxidant actions of ABX at physiological
      concentrations are, at least partially, mediated by TrxR and/or Trx system.

PMID- 24103202
TI  - [Early secretory antigenic target protein-6/culture filtrate protein-10 fusion
      protein-specific Th1 and Th2 response and its diagnostic value in tuberculous
      pleural effusion].
AB  - OBJECTIVE: To detect the Th1 and Th2 cell percentage in pleural effusion
      mononuclear cells (PEMCs) stimulated by early secretory antigenic target protein
      6 (ESAT-6)/culture filtrate protein-10 (CFP-10) fusion protein (E/C) with flow
      cytometry (FCM), and therefore to explore the local antigen specific Th1 and Th2
      response and its diagnostic value in tuberculous pleuritis. METHODS: Forty
      patients with tuberculous pleural effusion and 30 patients with malignant pleural
      effusion were included in this study from Sep.2008 to Mar.2009. PEMCs were
      isolated and cryopreserved. After resuscitation, the cells were cultured with E/C
      (simultaneously with positive control and negative control), and antigen-specific
      Th1 and Th2 cells were detected with intracellular cytokine staining of FCM.
      Normal distribution data using t test, abnormal distribution data using Wilcoxon
      test. RESULTS: In the TB group,the medians (quartile range) of Th1 cells and
      Th1/Th2 ratio among PEMCs stimulated by ESAT-6/CFP-10 fusion protein were 3.06%
      (1.59%-6.92%) and 17 (7.38-35.53), significantly higher than those of the
      negative control [0.38% (0.02%-1.80%) and 3.59 (0.49-25.09)], the differences
      being statistically significant (Z = -5.345 and 3.314, P < 0.01). The percentage
      of Th2 cells [(0.22 +/- 0.19)%] was also increased compared with that of the
      negative control [(0.10 +/- 0.08)%], the difference being statistically
      significant (t = 4.108, P < 0.01). In the malignant effusion group, the medians
      (quartile range) of Th1 percentage and Th1/Th2 ratio were 0.12% (0.05%-0.39%) and
      1.05 (0.25-2.52), which were significantly different as compared with those of
      the TB group (Z = -6.624 and -5.536, P < 0.01). The Th2 percentage in the 2
      groups were (0.22 +/- 0.19)% and (0.15 +/- 0.02)%, respectively (t = 1.954, P >
      0.05). The receiver operating characteristic curve indicated that the area under
      the curve (AUC), sensitivity, and specificity were 0.937, 85.4%, and 90.6%
      respectively for Th1 to diagnose tuberculous pleurisy. For Th1/Th2, the AUC,
      sensitivity, and specificity were 0.883, 81.5%, and 90.6% respectively.
      CONCLUSIONS: The feature of ESAT-6/CFP-10 fusion protein-specific Th1 and Th2
      response in tuberculous pleurisy was a mixed reaction of Th1 and Th2 with Th1
      predominance. Th1 percentage and Th1/Th2 ratio could be diagnostic indexes for
      identifying tuberculous from malignant pleural effusions.

PMID- 24103203
TI  - [Analysis of resistance tendency of bloodstream-infecting pathogens in China].
AB  - OBJECTIVE: To investigate the resistance profiles and the trend of bloodstream
      infecting pathogens isolated from hospitalized patients during 2004-2010.
      METHODS: The bloodstream isolates were collected from 18 hospitals in 17 cities.
      Minimum inhibition concentrations (MIC) were determined using the agar dilution
      method recommended by CLSI (Clinical and Laboratory Standards Institute), and
      susceptibility results were analyzed according to the 2011 CLSI guideline.
      RESULTS: Among the 2004-2005, 2007-2008 and 2009-2010 periods, the proportions of
      clinical isolates were similar; 43.1% (149 isolates), 34.0% (151 isolates) and
      47.5% (776 isolates) for Gram positive strains, 56.9% (197 isolates), 66.0% (293
      isolates) and 52.5% (858 isolates) for Gram negative strains, respectively. The
      isolating rate of MRSA was 54.1% (20/37) in 2007-2008, which was the highest
      among the 3 periods during 2004 to 2010, while it decreased in 2009-2010 (36.5%,
      62/170). The MRCNS proportions were similar across the 3 periods. One (1.8%)
      vancomycin-resistant Enterococcus faecium and 1 linezolid-resistant Enterococcus
      faecalis were found. Although the isolating rates of penicillin non-sensitive
      strains (oral) were similar between 2009-2010 and 2007-2008 [54.5% (6/11) and
      53.9% (7/13), respectively], the resistant rates increased from 0% in 2007-2008
      to 30.8% (4/13) in 2009-2010. The results were similar according to the non
      meningitis criterion (IV), and the susceptibility rates decreased from 100.0% (11
      isolates) in 2007-2008 to 84.6% (11/13) in 2009-2010. ESBL-harboring strains in
      E. coli were similar among the 3 periods during 2004 to 2010 [66.7% (30/45),
      73.2% (71/97) and 67.9% (233/343), respectively]. ESBL-producing strains in
      Klebsilla pnuemoniae decreased year after year, 72.4% (21/29), 50.0% (18/36) and
      41.1% (65/158) in 2004-2005, 2007-2008 and 2009-2010, respectively. Except that
      the sensitive rate of Enterobacter cloacae to ertapenem was 80% (32/40), the
      sensitive rates of other strains to carbapenems were still above 90% and the
      resistance rates were less than 5%. Acinetobacter baumannii had the highest multi
      drug resistance rate (81.8%, 81/99). One strain (1.0%, 1/99) of Acinetobacter
      baumannii isolated in 2009-2010 was reported to be pan-resistant. CONCLUSIONS: We
      are facing a more serious situation of bacterial resistance. Acinetobacter
      baumannii resistance was most serious, usually with the characteristics of
      multiple drug resistance, and even pan-resistance. Carbapenems remain to be the
      most effective against enterobacteriaceae. Strains resistant to novel antibiotics
      (linezolid and tigecycline) have emerged.

PMID- 24103204
TI  - [Investigation of smoking status and tobacco control in hospital staffs in
      Shanghai during 2010-2011].
AB  - OBJECTIVE: To identify the current status of smoking in hospital staffs and their
      ability to participate in tobacco control, and therefore to increase their
      awareness and active behavior on tobacco control. METHODS: A total of 9330
      hospital staffs from clinical, administrative, logistic and laboratory diagnosis
      departments in 78 hospitals located in various districts in Shanghai were
      surveyed with a questionnaire on smoking status and tobacco control from
      September 2010 to June 2011. The questionnaire mainly included the basic
      information and smoking status of the participants, as well as the tobacco
      control ability of the hospitals. RESULTS: The total smoking rate in Shanghai
      hospital staffs was 21.8% (2036/9330) .The proportion of smoking in males (chi(2)
      = 1751.09, P < 0.01) , in the 41-50 age group (chi(2) = 84.610, P < 0.01) and the
      associate degree (chi(2) = 509.068, P < 0.01) group were significant higher than
      those in the other groups. The most frequent reasons for smoking were relieving
      nervous tension which accounting for 40.5% (825/2036) and habits which accounting
      for 54.3% (1106/2036). The average score of the Fagerstrom Test of Nicotine
      Dependence (FTND) was 3.75 +/- 2.63, which was generally considered as mild
      dependence on nicotine. 56.9% (1158/2036) of the hospital staffs had the history
      of smoking cessation but the major reason for unwillingness to try quitting was
      worrying about failure to quit, which accounted for 67.9% (1382/2036). 94.3%
      (8798/9330) of the hospital staffs had a good awareness of common diseases
      associated with smoking, but only 33.7% (3144/9330) of them had a better
      comprehension of smoking cessation scientific methods, such as nicotine
      replacement drugs. 52.0% (3456/6643) of the doctors had asked patients whether
      they were smoking while only 24.9% (1654/6643) of them had suggested them to quit
      smoking. Even more, as many as 81.7% (5427/6643) of the doctors did not write
      orders of smoking cessation in their practice. CONCLUSION: The results indicate
      that it is necessary to carry out tobacco control training and to improve the
      awareness of tobacco control for hospital staffs, and more detailed instruction
      for smoke cessation and service are needed for the patients.

PMID- 24103205
TI  - [The clinicopathological features of acute fibrinous and organizing pneumonia].
AB  - OBJECTIVE: To improve understanding of the clinical, radiological and
      pathological characteristics of acute fibrinous and organizing pneumonia (AFOP).
      METHODS: The clinical data of 5 AFOP patients were retrospectively analyzed. AFOP
      was diagnosed via percutaneous lung biopsy guided by chest computerized
      tomography (CT) in the Affiliated Drum Tower Hospital of Nanjing University
      Medical School during March 2011 to June 2012. The clinical, radiological and
      pathological characteristics of those patients were summarized. RESULTS: Among
      the 5 patients, 2 were male and 3 were female, aging 43-61 years. They were all
      subacute onset. The main clinical manifestations were dyspnea, productive cough,
      fever and chest pain with hypoxemia via blood gas analysis. Bilateral infiltrates
      with diffuse and pathy distribution were the predominant features in chest HRCT.
      The pathological examination revealed slightly widened alveolar septa, 1ymphocyte
      and plasma cell infiltration and the presence of intra-alveolar fibrin in the
      form of fibrin "balls" (organization) within the alveolar spaces. No neutrophil,
      and eosinophil infiltration and hyaline membrane formation were detected, which
      was different from other well-recognized histologic patterns of acute lung
      injury, such as diffuse alveolar damage, cryptogenic organizing pneumonia and
      eosinophilic pneumonia. All patients were treated by corticosteroids and showed
      significant clinical and radiological improvement. CONCLUSIONS: AFOP has
      nospecific features, and its diagnosis depends on pathological examination.
      Treatment with corticosteroids is optimal. However, whether it is a unique
      interstitial disease needs to be further clinically investigated.

PMID- 24103206
TI  - [Clinical application of a fully covered self-expandable metallic stent in
      treatment of airway fistula].
AB  - OBJECTIVE: To assess the feasibility, safety and efficacy of the use of a fully
      covered self-expandable stent for the treatment of airway fistula. METHODS: From
      August 2005 to November 2011, 9 patients underwent treatment by the introduction
      of a tracheo-bronchial or bronchial fully covered self-expandable metallic stent.
      There were 7 males and 2 females, aged from 28-65 years with a mean of 46 years.
      In this group, 7 cases were diagnosed as bronchopleural fistula, 1 case as
      tracheopleural fistula, 1 case as broncho-esophageal fistula, 8 cases with
      thoracic empyema. The fistula orifices were from 3.5-25.0 mm in diameter with a
      mean 8.4 mm. All patients received topical anesthesia, and L-shaped stent was
      placed in 6 patients and I-shaped stent in 3 patients under fluoroscopic
      guidance. After the stent placement, the patients with empyema were treated with
      continual irrigation of the empyema cavity. RESULTS: Stent placement in the
      tracheo-bronchial tree was technically successful in all patients, without
      procedure-related complications. The operating time was from 5-16 minutes, mean
      time (10 +/- 4) minutes. Except for 1 patient, immediate closure of the airway
      fistula was achieved in the other patients after the procedure, as shown by the
      immediate cessation of bubbling in the chest drain system or the contrast
      examination. In this study, 1 patient coughed the inserted stent out due to
      irritable cough on the 5th day and had to receive repositioning of a new stent.
      Among the patients who were with empyema, 1 patient died of septicemia on the 8th
      day and 1 patient died of brain metastases from lung cancer 6 months after the
      stent insertion with empyema not cured, the other 6 patients' empyema healed from
      2-5 months, mean time 3.7 months. Seven patients were followed from 3 to 36
      months with a median of 13.5 months. During follow-up, 1 stent was removed from a
      patient 8 months after the stent implantation without empyema recurred. The
      remaining patient presented good tolerability to the existence of stent. The
      stents remained stable, no migration occurred, no empyema recurred, and the
      patient with broncho-esophageal fistula fed and drunk well. CONCLUSION: The use
      of fully covered self-expandable stents proved to be a safe, effective and fast
      minimally invasive method to treat airway fistula, especially for patients with a
      higher surgical risk or other failed treatments.

PMID- 24103207
TI  - [The influence of intermittent hypoxia on long-term facilitation of hypoglossal
      nerve discharge in spontaneously breathing rats].
AB  - OBJECTIVE: To explore the impact of intermittent hypoxia on long-term
      facilitation (LTF) of hypoglossal nerve discharge. METHODS: Twelve adult SD rats
      were divided into the experimental group (CIH group, n = 6) and the control group
      (normoxia group, n = 6) by the random number table. The rats in the CIH group
      were fed in the intermittent hypoxia animal chambers, while the control group was
      placed in the normoxia animal chambers for 8 h per day (from 8:00 AM to 4:00 PM)
      for 4 consecutive weeks. After that, 5 min*3 stimulations of acute intermittent
      hypoxia (AIH) were administered and the hypoglossal never signals were recorded
      before and after AIH. RESULTS: The baseline frequency and average peak amplitude
      of hypoglossal nerve discharge in the CIH experimental group were significantly
      greater than those in the control group. The discharge frequency in the CIH and
      the control groups was (73 +/- 13) Hz, and (58 +/- 11) Hz, respectively(P <
      0.05); and the discharge amplitude in the 2 groups was (4.6 +/- 1.1) uV, and (3.3
      +/- 0.7) uV, respectively(P < 0.05). After intervention with AIH, the frequency
      and the average peak amplitude of the hypoglossal nerve discharge in the
      experimental and the control groups were significantly increased(all P < 0.05).
      The increased discharge lasted more than 1 h and this typical phenomenon was
      referred to as LTF. In the CIH group, the discharge frequency before and after
      exposure to AIH was (68 +/- 16) Hz and (133 +/- 20) Hz, respectively; and the
      discharge amplitude was (4.6 +/- 1.1) uV and (8.9 +/- 1.4) uV, respectively. In
      the control group, the discharge frequency before and after AIH was (59 +/- 12)
      Hz and (102 +/- 16) Hz, respectively; and the discharge amplitude was (3.3 +/-
      0.7) uV and (4.5 +/- 0.7) uV, respectively(P < 0.05). After AIH stimulation, the
      enhanced respiratory intensity of rats in CIH group was much higher than that in
      the control group [(408 +/- 149)% vs (242 +/- 31)%, P < 0.05]. CONCLUSION: Both
      AIH and CIH can induce LTF of the hypoglossal nerve discharge, while the
      induction of LTF by AIH can be strengthened by CIH.

PMID- 24103208
TI  - [The proteasome inhibitor MG132 attenuates skeletal muscle atrophy in a rat model
      of chronic obstructive pulmonary disease].
AB  - OBJECTIVE: To investigate the effect of the proteasome inhibitor MG-132 on
      skeletal muscle atrophy in a rat model of chronic obstructive pulmonary disease
      (COPD) and its potential mechanisms. METHODS: The COPD rat model was established
      by instillation of LPS and exposure to the cigarette smoke. Then the COPD rats
      were randomly divided into 3 groups (each group n = 12): COPD model control
      group, MG-132 high dose group (MG-132 0.1 mg.kg(-1).d(-1)) and low dose group (MG
      132 0.05 mg.kg(-1).d(-1)), and normal control group. After 1 week and 4 week, 6
      rats of each group were sacrificed, and then the following parameters were
      determined: the weight of the diaphragm muscle, the concentration of TNF-alpha in
      the serum and diaphragm via enzyme-linked immunosorbent assay (ELISA). Muscle
      atrophy F-box protein (MAFbx), NF-kappaBp65, and IkappaB-alpha mRNA levels were
      determined by RT-PCR. The protein levels of MAFbx, NF-kappaBp65 and IkappaB-alpha
      in diaphragm were measured by Western blot. The single factor analysis of
      variance was used for statistical analysis among the groups, while t test was
      used for comparison between 2 groups, and Pearson linear correlation analysis was
      also performed. RESULTS: The weight of diaphragm muscle from 1 week and 4 week
      normal control group [(0.99 +/- 0.06) mg and (1.20 +/- 0.04) mg] were reduced as
      compared to those of COPD model control group [(0.83 +/- 0.09) mg and (1.01 +/-
      0.06) mg], high dose group [(0.85 +/- 0.02) mg and (1.11 +/- 0.06) mg], and low
      dose group [(0.83 +/- 0.03) mg and (1.04 +/- 0.02) mg]. The reduction of
      diaphragm muscle weight in the high dose group and the low dose group was
      significantly less than that in the COPD model control group, with a more marked
      difference as compared with the 4 week high dose group. The TNF-alpha levels in
      diaphragm from 4 week high dose group [(106 +/- 8) ng/L] and low dose group [(122
      +/- 7) ng/L] were decreased as compared to that of the COPD model control group
      [(143 +/- 24) ng/L]. The levels of NF-kappaBp65 and MAFbx mRNA from the 4 week
      high dose group (2.17 +/- 0.42) and low dose group (1.74 +/- 0.14) and the
      protein expression (1.13 +/- 0.04 and 1.27 +/- 0.05) were also decreased as
      compared to those of the COPD model control group (mRNA 2.81 +/- 0.31 and 4.87 +/
      0.34, protein expression 1.32 +/- 0.04 and 1.44 +/- 0.07). The levels of IkappaB
      alpha mRNA and protein expression (0.96 +/- 0.08 and 0.83 +/- 0.06) were higher
      than those of the COPD model control group (0.25 +/- 0.02 and 0.58 +/- 0.06), (t
      = 1.57-24.9, P < 0.05). The levels of the TNF-alpha levels in serum and diaphragm
      were correlated positively with the levels of MAFbx and NF-kappaBp65 mRNA and
      protein expression (r = 0.672-0.875, P < 0.01), but negatively with the levels of
      IkappaB-alpha mRNA and protein expression (r = -0.656--0.927, P < 0.01).
      CONCLUSIONS: The proteasome inhibitor MG-132 significantly inhibited IkappaB
      alpha degradation thus preventing NF-kappaB activation. This effect resulted in
      preventing skeletal muscle atrophy in the COPD rats.

PMID- 24103209
TI  - [Application of fluorine-18 fluorodeoxyglucose-positron emission tomography in
      the diagnosis and therapy of patients with sarcoidosis].

PMID- 24103210
TI  - [The progress on allergen-specific immunotherapy for bronchial asthma].

PMID- 24103212
TI  - [Fulminant sepsis due to Capnocytophaga canimorsus: Diagnosis by matrix-assisted
      laser desorption/ionization-time of flight mass spectrometry].

PMID- 24103211
TI  - Plasma brain derived neurotrophic factor (BDNF) and response to ketamine in
      treatment-resistant depression.
AB  - Ketamine produces rapid antidepressant effects in treatment-resistant depression
      (TRD), but the magnitude of response varies considerably between individual
      patients. Brain-derived neurotrophic factor (BDNF) has been investigated as a
      biomarker of treatment response in depression and has been implicated in the
      mechanism of action of ketamine. We evaluated plasma BDNF and associations with
      symptoms in 22 patients with TRD enrolled in a randomized controlled trial of
      ketamine compared to an anaesthetic control (midazolam). Ketamine significantly
      increased plasma BDNF levels in responders compared to non-responders 240 min
      post-infusion, and Montgomery-Asberg Depression Rating Scale (MADRS) scores were
      negatively correlated with BDNF (r=-0.701, p = 0.008). Plasma BDNF levels at 240
      min post-infusion were highly negatively associated with MADRS scores at 240 min
      (r = -0.897, p=.002), 24 h (r = -0.791, p = 0.038), 48 h (r = -0.944, p = 0.001)
      and 72 h (r = -0.977, p = 0.010). No associations with BDNF were found for
      patients receiving midazolam. These data support plasma BDNF as a peripheral
      biomarker relevant to ketamine antidepressant response. 

PMID- 24103213
TI  - A socio-technical systems approach to studying interruptions: understanding the
      interrupter's perspective.
AB  - The purpose of this study was to understand the cognitive processes underlying
      nurses' decision to interrupt other nurses. The Institute of Medicine (2000)
      reported that interruptions are likely contributors to medical errors.
      Unfortunately, the research to date has been quite homogenous, focusing only on
      the healthcare provider being interrupted, ignoring the true complexities of
      interruptions. This study took a socio-technical approach being the first to
      examine interruptions from the viewpoint of the interrupting nurse. Over 15 h of
      observations and 10 open-ended interviews with expert nurses in a Neuroscience
      Surgical Intensive Care Unit were conducted. It was found that nurses conduct a
      quick cost-benefit assessment to determine the interruptibility of other nurses
      and whether an interruption is value-added vs. non-value added. To complete the
      assessment, nurses consider several conditional factors related to the
      interruptee, the interrupter, and the nature of the interruption content, and
      different potential consequences of the interruption. 

PMID- 24103214
TI  - The yeast model system as a tool towards the understanding of apoptosis
      regulation by sphingolipids.
AB  - It has been established that sphingolipids are engaged in the regulation of
      apoptosis both as direct executors and as signalling molecules. However, the
      peculiarities of this class of bioactive lipids, namely the interconnectivity of
      their metabolic pathways, the specific subcellular localization where they are
      generated and the transport mechanisms involved, introduce a considerably high
      level of complexity in deciphering their role in the signalling and regulation of
      programmed cell death. Although yeast is undeniably a simple model, the
      conservation of the sphingolipid metabolism and of the core machinery engaged in
      regulated cell death has already provided valuable clues to the understanding of
      metabolic pathways involved in distinct cellular processes, including apoptosis.
      It can be anticipated that studies using this model system will further unravel
      mechanisms underlying the regulation of apoptosis by sphingolipids and contribute
      to novel therapeutic strategies against serious human diseases associated with
      dysfunction of sphingolipid-dependent cell death programmes. 

PMID- 24103215
TI  - Abdominal surgical site infections: a prospective study of determinant factors in
      Harare, Zimbabwe.
AB  - Surgical site infections (SSIs) are reported in lower frequencies in the
      developed countries than in the developing world. A prospective evaluation of
      risk factors in 285 patients undergoing abdominal surgery procedures in Zimbabwe
      was therefore undertaken. Overall infection rate was 26%. The age group 30-39
      years had the highest number of dirty wounds and the highest rate of human
      immunodeficiency virus (HIV) infection. Multivariate regression analysis showed a
      correlation between wound class and SSI (P < 0.05). This was also noted for
      American Society of Anesthesiologists (ASA) score (P < 0.05). HIV-infected
      patients had 52% SSIs and non-infected patients had 26% (P < 0.05). Patients
      receiving blood transfusion had 51% SSIs and those not transfused had 17% (P <
      0.01). Patients receiving pre- and intra-operative prophylactic antibiotics had
      18% SSIs and those receiving postoperative administration had 37% (P < 0.01).
      Treatment ranged from dressings only in 11% to surgical intervention in 30%
      resulting in prolongation of median hospital stay from 8 to 18 days (P < 0.001).
      Mortality was 7%. High wound class, high ASA score, blood transfusion, HIV
      infection and delayed use of prophylactic antibiotics were risk factors for SSIs,
      resulting in surgical interventions, prolonged hospital stay and mortality. 

PMID- 24103216
TI  - Digital ankle-brachial index technology used in primary care settings to detect
      flow obstruction: a population based registry study.
AB  - BACKGROUND: Peripheral artery disease affects 8-18 million people in the United
      States. Patients with peripheral artery disease are known to have increased
      morbidity and mortality. Medical guidelines recognize ankle-brachial index
      testing as an effective screening tool that allows for early detection of this
      disease in primary care settings. Doppler ankle-brachial index, the standard
      method used, is time consuming and requires technical expertise. Automated
      (digital) ankle-brachial index testing through plethysmography may be a more
      attractive method in primary care settings due to its speed and ease of use. This
      observational study evaluated the use of one digital ankle-brachial index device
      in primary care settings to describe the population tested and the results
      obtained. RESULTS: A total of 19 medical practices throughout the United States
      provided data on 632 patient tests. In the population tested, the mean age was
      67.2 (+/-13.8) years, and 38% of patients were male. Additionally, 94.7% of the
      population had risk factors, signs and/or symptoms suspicious for peripheral
      artery disease, and 20.3% presented with claudication. Twelve percent (76/632) of
      patient tests showed an abnormal digital ankle-brachial index (<0.93), indicating
      a result positive for peripheral artery disease; the frequency of
      hypercholesterolemia, hypertension, and coronary artery disease in this group was
      62% (45/73), 69% (50/72) and 46% (34/74), respectively. CONCLUSION: The results
      of this study support the use of a digital ankle-brachial index device using
      blood volume plethysmography technology for evaluation of peripheral artery
      disease. Data is consistent with previously reported population characteristics
      with respect to peripheral artery disease prevalence, signs/symptoms, and risk
      factors. The device used in this study enabled evaluation for peripheral artery
      disease in primary care settings and may allow for early detection of the
      disease.

PMID- 24103217
TI  - Analytical validation of the Oncotype DX prostate cancer assay - a clinical RT
      PCR assay optimized for prostate needle biopsies.
AB  - BACKGROUND: The Oncotype DX Prostate Cancer Assay is a multi-gene RT-PCR
      expression assay that was developed for use with fixed paraffin-embedded (FPE)
      diagnostic prostate needle biopsies containing as little as 1 mm of prostate
      tumor in the greatest dimension. The assay measures expression of 12 cancer
      related genes representing four biological pathways and 5 reference genes which
      are algorithmically combined to calculate the Genomic Prostate Score (GPS). This
      biopsy-based assay has been analytically and subsequently clinically validated as
      a predictor of aggressive prostate cancer. The aim of this study was to validate
      the analytical performance of the Oncotype DX Prostate Cancer Assay using
      predefined acceptance criteria. RESULTS: The lowest quartile of RNA yields from
      prostate needle biopsies (six 5 MUm sections) was between 19 and 34 ng.
      Analytical validation of the process requiring as little as 5 ng of RNA met all
      pre-defined acceptance criteria. Amplification efficiencies, analytical
      sensitivity, and accuracy of gene assays were measured by serially diluting an
      RNA sample and analyzing features of the linear regression between RNA expression
      measured by the crossing point (Cp) versus the log2 of the RNA input per PCR
      assay well. Gene assays were shown to accurately measure expression over a wide
      range of inputs (from as low as 0.005 ng to 320 ng). Analytical accuracy was
      excellent with average biases at qPCR inputs representative of patient samples
      <9.7% across all assays while amplification efficiencies were within +/-6% of the
      median. Assessments of reproducibility and precision were performed by testing 10
      prostate cancer RNA samples over multiple instruments, reagent lots, operators,
      days (precision), and RNA input levels (reproducibility) using appropriately
      parameterized linear mixed models. The standard deviations for analytical
      precision and reproducibility were 1.86 and 2.11 GPS units (100-unit scale)
      respectively. CONCLUSIONS: The Oncotype DX Prostate Cancer Assay, a clinical RT
      PCR assay specifically designed for use with prostate needle biopsies, has been
      analytically validated using very limited RNA inputs. The assay requirements and
      analytical performance will provide physicians with test results from a robust
      and reliable assay which will enable improved treatment decisions for men
      diagnosed with early-stage prostate cancer.

PMID- 24103218
TI  - Economic and environmental assessment of propionic acid production by
      fermentation using different renewable raw materials.
AB  - Production of propionic acid by fermentation of glycerol as a renewable resource
      has been suggested as a means for developing an environmentally-friendly route
      for this commodity chemical. However, in order to quantify the environmental
      benefits, life cycle assessment of the production, including raw materials,
      fermentation, upstream and downstream processing is required. The economic
      viability of the process also needs to be analysed to make sure that any
      environmental savings can be realised. In this study an environmental and
      economic assessment from cradle-to-gate has been conducted. The study highlights
      the need for a highly efficient bioprocess in terms of product titre (more than
      100g/L and productivity more than 2g/(L . h)) in order to be sustainable. The
      importance of the raw materials and energy production for operating the process
      to minimize emissions of greenhouse gases is also shown.

PMID- 24103219
TI  - Vacuum immobilisation reduces tumour excursion and minimises intrafraction error
      in a cohort study of stereotactic ablative body radiotherapy for pulmonary
      metastases.
AB  - INTRODUCTION: The purpose of this study is to assess the impact of a vacuum
      immobilisation system on reproducibility of patient set-up, interfraction
      stability and tumour motion amplitude. METHODS: From February 2010 to February
      2012 as part of a prospective clinical trial 12 patients with solitary pulmonary
      metastases had consecutive four-dimensional computed tomography (4DCT) scans
      performed with and without vacuum immobilisation. The displacement of the tumour
      centroid position was recorded in each of the 10 phases of the 4DCT
      reconstruction. A further six patients with seven metastases underwent single
      fraction stereotactic ablative body radiotherapy (SABR) during this period (a
      total of 19 targets) and were included in an analysis of positional
      reproducibility and intrafraction immobilisation. Couch shifts recorded in the
      medio-lateral (X), cranio-caudal (Y) and ventero-dorsal (Z) planes. RESULTS: For
      the 19 treatments delivered, the median (0-90% range) shift required immediately
      pretreatment was 1 mm (0-3) in the X-plane, 2 mm (0-6) in the Y-plane and 4 mm (0
      8) in the Z-plane, respectively. The mean (+/- standard deviation) of mid
      treatment shifts were 0.3 mm (+/- 0.7), 1.1 mm (+/- 2) and 0.8 mm (+/- 1.5) in
      the X, Y and Z planes, respectively. Mid-treatment shifts were <2 mm in all
      directions (P = < 0.001). The length of treatment time correlated to the required
      shifts in the Z plane (r(2)  = 0.377, P = 0.005), but not in the X or Y planes (P
      = 0.198 and P = 0.653, respectively). In the subset of 12 patients who had two
      4DCTs, the median (range) amplitude of tumour displacements in the X, Y and Z
      planes when immobilised were 0.9 mm (0.3-2.9), 2.6 mm (0.2-10.6) and 1.6 mm (0.5
      5.5), respectively. Immobilisation reduced the volume of tumour displacement
      during respiration by a median of 52.6% (P = 0.021). CONCLUSIONS: Vacuum
      immobilisation reduces total tumour excursion, facilitates reproducible
      positioning and provides robust intrafractional immobilisation during SABR
      treatments for pulmonary metastases.

PMID- 24103220
TI  - Psychological distress and quality of life in older persons: relative
      contributions of fixed and modifiable risk factors.
AB  - BACKGROUND: With a rapidly ageing population and increasing life expectancy,
      programs directed at improving the mental health and quality of life (QOL) of
      older persons are extremely important. This issue may be particularly relevant in
      the aged-care residential sector, where very high rates of depression and poor
      QOL are evident. This study aims to investigate the fixed and modifiable risk
      factors of psychological distress and QOL in a cohort of Australians aged 60 and
      over living in residential and community settings. METHODS: The study examined
      the relationship between demographic, health and lifestyle factors and the
      outcome variables of self-reported QOL and psychological distress (K10 scores)
      based on data from 626 Australians aged 60 and over from the 45 and Up Study
      dataset. Univariate and multivariate regression analyses (performed on a subset
      of 496) examined risk factors related to psychological distress and QOL adjusting
      for age and residential status. RESULTS: Significant psychological distress was
      experienced by 15% of the residential sample and 7% of the community sample and
      in multivariate analyses was predicted by older age, more functional limitations,
      more time spent sleeping and lower levels of social support (accounting for 18%
      of the variance). Poorer QOL was predicted by more functional limitations and
      greater levels of psychological distress. Together these variables accounted for
      35% of the variance in QOL ratings. CONCLUSIONS: While psychological distress was
      more common in residential settings, programs targeting modifiable risk factors
      have the potential to improve QOL and reduce psychological distress in older
      persons living in both residential and community settings. In particular,
      promoting health and mobility, optimising sleep-wake cycles and increasing social
      support may reduce levels of psychological distress and improve QOL.

PMID- 24103222
TI  - Hot and humid: a bad combination for you, me, and patients with arrhythmogenic
      right ventricular dysplasia/cardiomyopathyCalkins.

PMID- 24103221
TI  - The COR trial: a randomized study with continuous rhythm monitoring to compare
      the efficacy of cryoenergy and radiofrequency for pulmonary vein isolation.
AB  - BACKGROUND: Results from randomized trials designed to compare cryoenergy with
      radiofrequency for pulmonary vein (PV) isolation are lacking. OBJECTIVE: To
      compare the efficacy of a simplified strategy for PV cryoablation (group C) vs PV
      isolation with open-irrigated radiofrequency catheters (group R). METHODS: Fifty
      patients with paroxysmal atrial fibrillation (AF) and 4 independent PVs received
      a Reveal XT implantable cardiac monitor and were randomized to group C or group
      R. In group C, PV ablation was done with a single Arctic Front balloon (23 or 28
      mm) per patient and two 300-second applications per PV. No further applications
      were delivered to close residual conduction gaps. In group R, bidirectional PV
      conduction block was pursued with Lasso and Navistar ThermoCool catheters and the
      CARTO system. The primary end point was the proportion of patients remaining free
      from AF recurrences >=2 minutes without taking antiarrhythmic drugs 12 months
      after ablation. RESULTS: The primary end point was met by 12 (48%) patients in
      group C and 25 (68%) patients in group R (odds ratio 0.43; P = .05). This
      difference disappeared after adjustment for acute procedural outcome. In patients
      for whom all 4 PVs were blocked at the end of the procedure, there was no
      difference between group C and group R in the primary end point (67% vs 68%; P =
      .94). CONCLUSIONS: The efficacy of the simplified strategy for PV cryoablation
      tested in this study is inferior to PV isolation using open-irrigated
      radiofrequency catheters with electrophysiological and electroanatomical
      guidance. Complete PV conduction block is critical to the success of AF ablation.

PMID- 24103223
TI  - Successful epicardial ablation of electrical storms due to recurrent ventricular
      fibrillation triggered by premature ventricular contractions.

PMID- 24103224
TI  - Management of focal atrial tachycardias originating from the atrial appendage
      with the combination of radiofrequency catheter ablation and minimally invasive
      atrial appendectomy.
AB  - BACKGROUND: Focal atrial tachycardias (ATs) originating from the left and the
      right atrial appendage (AA) were the most difficult to eliminate. OBJECTIVE: To
      evaluate the safety and long-term efficacy of minimally invasive surgical atrial
      appendectomy in combination with radiofrequency catheter ablation (RFCA) in the
      management of focal atrial appendage tachycardias (AATs). METHODS: We included 42
      consecutive patients with 42 AATs confirmed by activation mapping and contrast
      venography. Thirty of them were successfully managed with RFCA (RFCA-successful
      group), while the remaining 12 (28.6%) finally resorted to video-assisted
      thoracoscopic atrial appendectomy owing to RFCA failure (resort-to-surgery
      group). We searched for predictors of RFCA failure, and the need for surgery by
      using a binomial logistic regression model. RESULTS: In the RFCA-successful
      group, 6 (20.0%) patients experienced recurrence and re-do ablation and 11
      (36.7%) AATs originated from distal AAs. In the resort-to-surgery group, the
      tachycardias involved exclusively distal AAs and required more RFCA attempts
      compared with those of the RFCA-successful group (1.58 +/- 0.51 vs 1.20 +/- 0.41;
      P = .0165). During atrial appendectomy, incessant ATs were terminated immediately
      after resection of the AA at the base. Long-term success was achieved in all 42
      patients with a follow-up of 29.1 +/- 17.5 months. No complications occurred.
      Fourteen patients with tachycardia-induced cardiomyopathy recovered fully. We
      identified origin at distal AATs and longer time to tachycardia termination by
      ablation as predictors of RFCA failure and the need for surgical intervention.
      CONCLUSION: ATs originating from the distal portion of AA were more refractory to
      RFCA. The combination of catheter ablation and video-assisted thoracoscopic
      atrial appendectomy was an effective strategy to manage AATs.

PMID- 24103225
TI  - Restoring the resting potential brings maturity to induced stem cell-derived
      human cardiac myocytes.

PMID- 24103226
TI  - Prevalence and spectrum of electroencephalogram-identified epileptiform activity
      among patients with long QT syndrome.
AB  - BACKGROUND: Congenital long QT syndrome (LQTS) is a heritable cardiac disease
      whereby patients are at an increased risk for LQTS-triggered syncope, seizures,
      and sudden cardiac arrest. Seizure episodes are common in LQTS and most often
      seen in patients with type 2 LQTS (LQT2). OBJECTIVE: To determine the prevalence
      of electroencephalogram (EEG)-identified epileptiform activity among patients
      with LQTS. METHODS: A retrospective electronic medical record review of 610
      patients with LQTS (250 [41%] men), evaluated between 2000 and 2012, was
      performed to identify (1) all patients with LQTS who presented with
      seizures/seizure-like episodes, (2) patients with LQTS who underwent a subsequent
      neurologic evaluation and EEG study, and (3) patients with LQTS and abnormal EEG
      recordings that showed epileptiform activity during sinus rhythm, confirming a
      seizure independent from cardiac arrhythmia. RESULTS: Overall, seizures/seizure
      like episodes were recorded in 68 of 610 (11%) patients with LQTS. Ten patients
      were diagnosed with a seizure disorder by an epileptologist on the basis of the
      clinical findings and EEG studies, giving a prevalence of 10 of 610 (1.6%; 95%
      confidence interval 0.8%-3%) among patients with LQTS. A diagnosis of epilepsy
      was overrepresented in patients with LQT2 (7 of 190 [3.7%]) in comparison to all
      other LQT subgroups (3 of 420 [0.7%]; P = .0126). CONCLUSIONS: While the overall
      prevalence of epilepsy among patients with LQTS is low, 10 of 68 (15%) of the
      patients who presented with seizures/seizure-like episodes had EEG-identified
      epileptiform activity. Confirming earlier observational reports, epilepsy is more
      common in patients with LQT2, further supporting the shared pathogenetic link
      hypothesis of this KCNH2-encoded potassium channel that is expressed in both the
      heart and the brain.

PMID- 24103227
TI  - Baseline characteristics and effects of ten years of growth hormone (GH)
      replacement therapy in adults previously treated with pituitary irradiation.
AB  - CONTEXT: Little is known of the importance of previous irradiation therapy for
      baseline characteristics and responsiveness to GH replacement in GH deficient
      (GHD) adults. OBJECTIVE/DESIGN/PATIENTS: In this prospective, single-centre, open
      label study, the effects of 10-year GH replacement were determined in 18 GHD
      adults that had previously received conventional external fractionated pituitary
      irradiation therapy (IRR group) and 18 non-irradiated GHD patients (non-IRR
      group). All patients had adult onset disease and complete deficiency of anterior
      pituitary hormones and both groups were comparable in terms of age, gender, body
      mass index (BMI), and waist:hip ratio. RESULTS: At baseline, IRR patients had
      higher serum triglyceride (TG) and insulin levels and lower high density
      lipoprotein (HDL)-cholesterol (HDL-C) level than non-IRR patients (all p<0.05).
      The 10-year GH replacement improved body composition, bone mass and serum lipid
      profile without any between-group differences, except for a marginally more
      beneficial response in serum TG level in the IRR patients. After 10 years, there
      was no between-group difference in any variable after correction for a higher
      replacement dose of glucocorticoids in the IRR patients at study end using an
      analysis of covariance. During the 10-year GH replacement, 5 IRR patients
      suffered from vascular events (2 fatal) whereas only one non-fatal vascular event
      occurred in the non-IRR patients. CONCLUSIONS: IRR patients with GHD display a
      more severely impaired cardiovascular risk profile at baseline, which was
      reversed by the 10-year GH replacement after correction for the higher
      glucocorticoid dose at study end. However, vascular events occurred more
      frequently in the IRR patients.

PMID- 24103228
TI  - Inclusion complexes of cypermethrin and permethrin with monochlorotriazinyl-beta
      cyclodextrin: a combined spectroscopy, TG/DSC and DFT study.
AB  - The suitable size hydrophobic cavity and monochlorotriazinyl group as a reactive
      anchor make MCT-beta-CD to be widely used in fabric finishing. In this paper, the
      inclusion complexes of monochlorotriazinyl-beta-cyclodextrin (MCT-beta-CD) with
      cypermethrin (CYPERM) and permethrin (PERM) are synthesized and analyzed by
      TG/DSC, FT-IR and Raman spectroscopy. TG/DSC reveals that the decomposed
      temperatures of inclusion complexes are lower by 25-30  degrees C than that of
      physical mixtures. DFT calculations in conjunction with FT-IR and Raman spectral
      analyses are used to study the structures of MCT-beta-CD and their inclusion
      complexes. Four isomers of trisubstituted MCT-beta-CD are designed and DFT
      calculations reveal that 1,3,5-trisubstituted MCT-beta-CD has the lowest energy
      and can be considered as main component of MCT-beta-CD. The ground-state
      geometries, vibrational wavenumbers, IR and Raman intensities of MCT-beta-CD and
      their inclusion complexes were calculated at B3LYP/6-31G (d) level of theory.
      Upon examining the optimized geometry of inclusion complex, we find that the
      CYPERM and PERM are inserted into the toroid of MCT-beta-CD from the larger
      opening. The band at 1646 cm(-1) in IR and at 1668 cm(-1) in Raman spectrum
      reveals that monochloroazinyl group of MCT-beta-CD exists in ketone form but not
      in anion form. The noticeable IR and Raman shift of phenyl reveals that these two
      benzene rings of CYPERM and PERM stays inside the cavity of MCT-beta-CD and has
      weak interaction with MCT-beta-CD. This spectroscopy conclusion is consistent
      with theoretical predicted structure.

PMID- 24103229
TI  - DFT calculations and electronic absorption spectra of some, alpha- and gamma
      pyrone derivatives.
AB  - The electronic absorption spectra of 6-ethyl-4-hydroxy-2,5-dioxo-pyrano[3,2-c]
      quinoline 1, 6-ethyl-4-hydroxy-3-nitro-2,5-dioxo-pyrano[3,2-c] quinoline 2, 6
      ethyl-4-chloro-2,5-dioxo-pyrano[3,2-c] quinoline 3, 6-ethyl-3-nitro-4-chloro-2,5
      dioxo-pyrano[3,2-c] quinoline 4, 6-ethyl-4,5-dioxopyrano[3,2-c] quinoline 5, and
      6-ethyl-3-nitro-6H-pyrano [3,2-c]quinoline-4,5-dione 6, were measured in polar
      (methanol) as well as nonpolar (dioxane) solvents. The geometries were optimized
      using B3LYB/6-311G (p,d) method. The most stable geometry of the studied
      compounds, 1-6, is the planar structure as indicates by the values of the
      dihedral angles. The insertion of a nitro group in position 3 in both alpha- and
      gamma-pyrone ring decreases the energy gap and hence increases the reactivity of
      3 and 6 compounds. Assignment of the observed bands as localized, delocalized
      and/or of charge transfer (CT) has been facilitated by TD-DFT calculations. The
      correspondences between the calculated and experimental transition energies are
      satisfactory. The solvent and substituent effects have been investigated. Chloro
      substituent has a higher band position and intensity effects on the spectra more
      than hydroxyl or nitro groups.

PMID- 24103230
TI  - Thermal annealing effects on multi-walled carbon nanotube yarns probed by Raman
      spectroscopy.
AB  - The realized mechanical properties of CNT macrostructures such as webs and yarns
      remain significantly lower than those of the individual CNTs. Structural changes
      induced by thermal annealing under inert atmosphere were assessed using Raman
      spectroscopy. Annealing above 1000  degrees C resulted in a marked decrease in
      the D/G ratio which can be attributed to an increase in the crystallite size or
      the distance between defects. The band component parameters obtained by spectral
      deconvolution reveal that the D band peak maximum shifts to slightly higher
      energy with increased annealing temperature. In contrast, the energy of the G
      band did not change. The full widths at half height (FWHH) of the D and G bands
      are seen to decrease with increasing annealing temperature. The tensile
      properties of the yarns have been investigated and it was found that the yarn
      tenacity did not improve with these structural changes. The effect of impurities
      in the annealing system such as oxygen, adsorbed water or organic surface
      contamination was also investigated.

PMID- 24103231
TI  - Spectral and structural studies of the anti-cancer drug Flutamide by density
      functional theoretical method.
AB  - A comprehensive screening of the more recent DFT theoretical approach to
      structural analysis is presented in this section of theoretical structural
      analysis. The chemical name of 2-methyl-N-[4-nitro-3-(trifluoromethyl)phenyl]
      propanamide is usually called as Flutamide (In the present study it is
      abbreviated as FLT) and is an important and efficacious drug in the treatment of
      anti-cancer resistant. The molecular geometry, vibrational spectra, electronic
      and NMR spectral interpretation of Flutamide have been studied with the aid of
      density functional theory method (DFT). The vibrational assignments of the normal
      modes were performed on the basis of the PED calculations using the VEDA 4
      program. Comparison of computational results with X-ray diffraction results of
      Flutamide allowed the evaluation of structure predictions and confirmed B3LYP/6
      31G(d,p) as accurate for structure determination. Application of scaling factors
      for IR and Raman frequency predictions showed good agreement with experimental
      values. This is supported the assignment of the major contributors of the
      vibration modes of the title compound. Stability of the molecule arising from
      hyperconjugative interactions leading to its bioactivity, charge delocalization
      have been analyzed using natural bond orbital (NBO) analysis. NMR chemical shifts
      of the molecule were calculated using the gauge independent atomic orbital (GIAO)
      method. The comparison of measured FTIR, FT-Raman, and UV-Visible data to
      calculated values allowed assignment of major spectral features of the title
      molecule. Besides, Frontier molecular orbital analyze was also investigated using
      theoretical calculations.

PMID- 24103232
TI  - NIH EXAMINER: conceptualization and development of an executive function battery.
AB  - Executive functioning is widely targeted when human cognition is assessed, but
      there is little consensus on how it should be operationalized and measured.
      Recognizing the difficulties associated with establishing standard operational
      definitions of executive functioning, the National Institute of Neurological
      Disorders and Stroke entered into a contract with the University of California
      San Francisco to develop psychometrically robust executive measurement tools that
      would be accepted by the neurology clinical trials and clinical research
      communities. This effort, entitled Executive Abilities: Measures and Instruments
      for Neurobehavioral Evaluation and Research (EXAMINER), resulted in a series of
      tasks targeting working memory, inhibition, set shifting, fluency, insight,
      planning, social cognition and behavior. We describe battery conceptualization
      and development, data collection, scale construction based on item response
      theory, and lay the foundation for studying the battery's utility and validity
      for specific assessment and research goals.

PMID- 24103234
TI  - Ultrasound, tracheal intubation and cardiopulmonary resuscitation: Isn't there
      enough to do during a cardiac arrest?

PMID- 24103233
TI  - The effect of adherence to ACLS protocols on survival of event in the setting of
      in-hospital cardiac arrest.
AB  - AIM: Advanced Cardiac Life Support (ACLS) algorithms are the default standard of
      care for in-hospital cardiac arrest (IHCA) management. However, adherence to
      published guidelines is relatively poor. The records of 149 patients who
      experienced IHCA were examined to begin to understand the association between
      overall adherence to ACLS protocols and successful return of spontaneous
      circulation (ROSC). METHODS: A retrospective chart review of medical records and
      code team worksheets was conducted for 75 patients who had ROSC after an IHCA
      event (SE group) and 74 who did not survive an IHCA event (DNS group). Protocol
      adherence was assessed using a detailed checklist based on the 2005 ACLS Update
      protocols. Several additional patient characteristics and circumstances were also
      examined as potential predictors of ROSC. RESULTS: In unadjusted analyses, the
      percentage of correct steps performed was positively correlated with ROSC from an
      IHCA (p<0.01), and the number of errors of commission and omission were both
      negatively correlated with ROSC from an IHCA (p<0.01). In multivariable models,
      the percentage of correct steps performed and the number of errors of commission
      and omission remained significantly predictive of ROSC (p<0.01 and p<0.0001,
      respectively) even after accounting for confounders such as the difference in age
      and location of the IHCAs. CONCLUSIONS: Our results show that adherence to ACLS
      protocols throughout an event is correlated with increased ROSC in the setting of
      cardiac arrest. Furthermore, the results suggest that, in addition to correct
      actions, both wrong actions and omissions of indicated actions lead to decreased
      ROSC after IHCA.

PMID- 24103235
TI  - [Neurological symptoms in children with intussusception].
AB  - INTRODUCTION: Intussusception is a potentially severe obstructive disease that
      occurs when a more proximal portion of bowel invaginates into a more distal part
      of the bowel. Patients with intussusception often present with a wide range of
      non-specific systemic symptoms, with less than one quarter presenting with the
      classic triad of vomiting, abdominal pain, and bloody stools. An acute change in
      level of consciousness could be the only clinical symptom of this disorder.
      OBJECTIVES: To ascertain the frequency and nature of the neurological symptoms in
      children with intussusception, and to describe the characteristics of the
      patients presenting in this atypical way. PATIENTS AND METHODS: We
      retrospectively reviewed the records of 351 children presenting with
      intussusception from 2000 to 2012. General epidemiological data, abdominal and
      neurological signs and symptoms, duration of symptoms and effectiveness of
      treatment, were analysed in all patients. RESULTS: Of the 351 patients studied,
      15 (4.27%) had one or more neurological symptoms recorded at presentation, with
      lethargy being the most frequent (66.66%), followed by hypotonia, generalized
      weakness, paroxysmal events, and fluctuating consciousness. Sixty per cent of
      these fifteen patients showed isolated neurological symptomatology, and eleven of
      them (73.3%) needed a laparotomy to reduce the intussusception. CONCLUSIONS:
      Intussusception should be considered in the differential diagnosis in infants and
      young children presenting as a pediatric emergency with lethargy, hypotonia,
      generalized weakness, paroxysmal events and/or sudden changes in consciousness,
      even in the absence of the classical symptoms of intussusception. An early
      recognition of intussusception may improve the global prognosis and avoid
      ischaemic intestinal sequelae.

PMID- 24103236
TI  - [Usefulness of a real-time quantitative polymerase-chain reaction (PCR) assay for
      the diagnosis of congenital and postnatal cytomegalovirus infection].
AB  - INTRODUCTION: Cytomegalovirus (CMV) is the main virus causing congenital and
      postnatal infections in the pediatric population. The aim of this study is to
      evaluate the usefulness of a quantitative real-time PCR in the diagnosis of these
      infections using urine as a single sample. PATIENTS AND METHODS: We studied all
      the urine samples of newborns (< 7 days) with suspected congenital infection, and
      urine of patients with suspected postnatal infection (urine negative at birth).
      Urines were simultaneously studied by cell culture, qualitative PCR (PCRc), and
      quantitative real-time PCR (PCRq). RESULTS: We analyzed 332 urine samples (270 to
      rule out congenital infection and 62 postnatal infections). Of the first, 22 were
      positive in the PCRq, 19 in the PCRc, and 17 in the culture. PCRq had a
      sensitivity of 100%, on comparing the culture with the rest of the techniques.
      Using the PCRq as a reference method, culture had a sensitivity of 77.2%, and
      PCRc 86.3%. In cases of postnatal infection, PCRq detected 16 positive urines,
      the PCRq 12, and the cell culture 10. The urines showed viral loads ranging from
      2,178 to 116,641 copies/ml. CONCLUSIONS: The genomic amplification technique PCRq
      in real time was more sensitive than the other techniques evaluated. This
      technique should be considered as a reference (gold standard), leaving the cell
      culture as a second diagnostic level. The low cost and the automation of PCRq
      would enable the screening for CMV infection in large neonatal and postnatal
      populations.

PMID- 24103237
TI  - [Neurocognitive and behavioral disturbances after adenotonsillectomy in
      obstructive sleep apnea syndrome].
AB  - INTRODUCTION: Adenotonsillectomy is an effective treatment for sleep-disordered
      breathing in children, but its ability to resolve neurocognitive issues, is not
      clear. OBJECTIVE: To analyze the outcomes of cognitive and behavioral disorders
      after one year of adenotonsillectomy. METHOD: We studied the behavioral and
      cognitive abnormalities in 45 children with obstructive sleep apnea and 30
      healthy controls, aged 3 to 13 years. Psychological tests were performed in both
      groups at baseline and at 12 months. RESULTS: Preoperatively, all cognitive and
      behavioral disturbances were higher in the study group than in the control group:
      attention in 46.7% of cases in the study group versus 20% in the control group
      (P=.016), anxiety 60.9% versus 40.9% (not significant); memory 55.6% versus 36.7%
      (P=.019), spatial structuring 64.4% versus 36.7% (P=.017), hyperactivity 42.9%
      versus 12.5% (P=.016), and attention deficit 46.4% versus 8.3% (P=.003). After
      one year we observed more disturbances in all variables in the study group.
      However, significant differences remained only in spatial structure (31.3% versus
      3.3%, P=.017), and attention deficit (40.5% versus 16.7%, P=.031). The
      percentages of patients that improved in one year were not significantly
      different between both groups. CONCLUSION: Behavioral and cognitive disturbances
      in children with sleep apnea were partially resolved following
      adenotonsillectomy. Improvements in the cognitive and behavioral variables did
      not differ significantly from those the normal evolution of the individual, and
      were independent of the resolution of respiratory disorders.

PMID- 24103238
TI  - [Extubation failure due to prolonged residual block after vecuronium. Treatment
      with sugammadex].

PMID- 24103239
TI  - [Imerslund-Grasbeck syndrome: megaloblastic anaemia with proteinuria].

PMID- 24103240
TI  - [Knowledge of health care ethics in paediatric residents].
AB  - INTRODUCTION: Bioethics has been recently incorporated in to the educational
      programs of both medical students and medical residents as part of their
      curriculum. However, its training based on clinical practice is not well
      structured. OBJECTIVE: To evaluate the knowledge of bioethics in Spanish
      paediatric residents, and to analyse how this relates to the medical education
      during graduate and post-graduate training. MATERIAL AND METHODS: A questionnaire
      with 20 multiple choice questions was designed to evaluate the knowledge in basic
      ethics with potential implications in clinical practice. We evaluated the
      education received during graduate and post-graduate training, and the main
      ethical conflicts faced. RESULTS: A total of 210 completed questionnaires were
      received from medical residents in paediatrics from 20 different Spanish
      hospitals, of whom 47 of these were first year residents (R1), 49 were second
      year residents (R2), 57 were third year residents (R3), and the remaining 57 were
      final year residents (R4). The mean number of correct answers was 16.8 out of 20.
      No differences were found between residents in different years of training, nor
      were there any differences between the group that had received specific training
      in bioethics versus those who had not. Residents were more likely to give wrong
      answers related with informed consent, the law on the freedom of the patient,
      principles of quality of life, the case analysis system, and the dimension of
      distributive justice. CONCLUSIONS: Limitation of therapeutic efforts was
      identified as the main ethical problem faced in clinical practice by Spanish
      residents in paediatrics. Most of the knowledge of bioethics is acquired during
      graduate training, and improved very little throughout the period of medical
      residence. Our results suggest that efforts are required in organising and
      structuring the education in bioethics during the training of residents in
      paediatrics.

PMID- 24103241
TI  - [Fever and skin lesions in a patient with chronic granulomatous disease].

PMID- 24103242
TI  - [Presentation of "Continuum": The continuing education portal of the Spanish
      Paediatric Association].

PMID- 24103243
TI  - [Use of peritoneal dialysis in newborns undergoing cardiac surgery with
      cardiopulmonary bypass].
AB  - INTRODUCTION: Renal replacement therapy is required in up to 10% of children
      undergoing cardiac surgery. Peritoneal dialysis (PD) is the preferred treatment
      method in the neonatal period. OBJECTIVE: To evaluate safety, efficacy and
      perioperative factors associated with the need for PD. MATERIAL AND METHODS:
      Retrospective review of clinical charts over a two-year period of newborns
      undergoing cardiac surgery with cardiopulmonary bypass (CPB). The group of cases
      requiring PD were compared with a group of random controls that did not require
      any renal replacement therapy. RESULTS: A total of 76 infants underwent cardiac
      surgery with CPB, of which 24 required PD. The need for PD was associated with
      low cardiac output in the immediate postoperative period and longer mechanical
      ventilation. The most frequent indication was fluid overload. The technique was
      effective in 66% of patients. Complications were only recorded in one patient.
      CONCLUSIONS: The most common indication for PD after cardiac surgery with CPB in
      neonates is fluid overload. The need for renal replacement therapy is associated
      with low cardiac output and a longer duration of mechanical ventilation. PD is an
      effective technique with few complications in these patients.

PMID- 24103244
TI  - [What can be done in the emergency department in the case of a bite from a dog
      with suspected rabies?].

PMID- 24103245
TI  - [Full blood count reference values in children of 8 to 12 years old residing at
      2,760 m above sea level].
AB  - OBJECTIVE: To determine reference values for full blood count parameters in a
      population of children 8 to 12 years old, living at an altitude of 2760 m above
      sea level. MATERIAL AND METHODS: Our sample consisted of 102 individuals on whom
      a full blood count was performed. The parameters included: total number of red
      blood cells, platelets, white cells, and a differential count (millions/MUl and
      %) of neutrophils, lymphocytes, monocytes, eosinophils and basophils.
      Additionally, we obtained values for hemoglobin, hematocrit, mean corpuscular
      volume, mean corpuscular hemoglobin, concentration of corpuscular hemoglobin and
      red blood cell distribution width. The results were statistically analyzed with a
      non-parametric test, to divide the sample in quartiles and obtain the lower and
      upper limits for our intervals. Moreover, the values for the intervals obtained
      from this analysis were compared to intervals obtained estimating+- 2 standard
      deviations above and below from our mean values. RESULTS: Our results showed
      significant differences compared to normal interval values reported for the adult
      Mexican population in most of the parameters studied. CONCLUSIONS: The full blood
      count is an important laboratory test used routinely for the initial assessment
      of a patient. Values of full blood counts in healthy individuals vary according
      to gender, age and geographic location; therefore, each population should have
      its own reference values.

PMID- 24103246
TI  - [Endocrinological outcome in children and adolescents survivors of central
      nervous system tumours after a 5 year follow-up].
AB  - INTRODUCTION: Given the successful increase in survival rates with the current
      treatments for central nervous system tumours (CNST), survivors are at high risk
      for late adverse effects. PURPOSE: To evaluate the endocrine sequelae in children
      with CNST according to the type of tumour and treatment received. PATIENTS AND
      METHODS: A retrospective review of the clinical features, auxology, hormone
      determinations and imaging findings of 38 patients (36.8% females, 63.2% males)
      with CNST, with a minimum of 5 years follow-up, was performed. RESULTS: The mean
      age at diagnosis was 5.34 +/- 3.07 years, with 76.3% of the patients having at
      least one hormone deficiency, of which growth hormone (GH) (73.7% of all
      patients) was the most prevalent, followed by thyrotropin (TSH) (68.4%),
      corticotropin (31.6%), antidiuretic hormone (28.9%), and gonadotropin (LH/FSH)
      (21.1%) deficiency. Precocious puberty was found in 21.1% of patients. After 5
      years of follow-up, 28.9% were obese. Craniopharyngioma had more hormone
      deficiencies, obesity and recurrence rates. The most frequently administered
      treatment was surgery + chemotherapy + radiotherapy, in 47.4% of the patients.
      Mean final height (20 patients) was -1.2 1.6 SDS, with a mean difference of -0.53
      SDS regarding their target height. CONCLUSIONS: 1) The type of tumour and
      treatment received influence the endocrinological sequelae. 2) The most frequent
      hormone deficiencies in all types of CNST, regardless of the treatment received,
      were GH and TSH. 3) Early diagnosis and prompt intervention of endocrine
      dysfunction can reduce the morbidity and improve quality of life over the long
      term.

PMID- 24103247
TI  - [Subcutaneous emphysema and pneumomediastinum after dental extraction].

PMID- 24103248
TI  - [Pott's puffy tumor: a rare complication of frontal sinusitis].
AB  - Pott's puffy tumor is a rare complication of frontal sinusitis characterized by
      swelling and edema in the brow due to a subperiosteal abscess associated with
      frontal osteomyelitis. Added complications are cellulitis by extension to the
      orbit and intracranial infection by posterior extension, with high risk of
      meningitis, intracranial abscess, and venous sinus thrombosis. Early diagnosis
      and aggressive medical or surgical treatment are essential for optimal recovery
      of affected patients. In the antibiotic age it is extremely rare, with very few
      cases described in the recent literature. A case is presented of a Pott
      inflammatory tumor in a 7 year-old boy, as a complication of acute pansinusitis
      who presented with front preseptal swelling and intracranial involvement with
      thrombosis of ophthalmic and superior orbital veins and frontal epidural abscess
      extending to the subarachnoid space. 

PMID- 24103249
TI  - [Pervasive developmental disorders screening program in the health areas of
      Salamanca and Zamora in Spain].
AB  - OBJECTIVE: To evaluate the results of the Pervasive Developmental Disorders (PDD)
      screening program currently ongoing in the public health services in the health
      area of Salamanca and Zamora, Spain, in terms of feasibility, reliability and
      costs, with the purpose of extending the program at regional and national levels.
      METHOD: A total of 54 paediatric teams (nurses and paediatricians) from the
      provinces of Salamanca and Zamora participated in the training sessions for the
      PDD Screening Programme in September 2005, and agreed to administer the
      questionnaire M-CHAT(1) to all parents attending their clinics in any of these
      two visits: 18 months and/or 24 months within the Well-baby Check-up Program. A
      total of 9,524 children have participated up to December 2012. Additionally, we
      evaluated the participation and opinions of the paediatric teams using
      questionnaires, and costs per positive case have estimated. RESULTS: Out of a
      total of 852 (8.9%) children determined as PDD high-risk with the M-CHAT
      questionnaire results, 61 (7.1%) were confirmed as positive with the M-CHAT
      follow-up interview. Of these, 22 were diagnosed with a PDD and 31 other
      disorders of childhood onset according to DSM-IV-TR(2). Almost three-quarters
      (74%) of respondents felt the program was totally feasible, and 22% viable, but
      with reservations (n=54). CONCLUSIONS: This study has been able to show for the
      first time in Spain, the feasibility of a population-based PDD screening program
      within the public health system. Training in social and communicative
      development, and dissemination of the early signs of PDD among paediatricians, as
      well as the use of the M-CHAT, is essential for progress in the early detection
      of these disorders.

PMID- 24103250
TI  - [Validation of an acute bronchiolitis severity scale].
AB  - INTRODUCTION: Acute bronchiolitis (AB) is a very common disease, with a high rate
      of seasonal hospitalization. Its management requires homogeneous clinical
      interpretations for which there are different approaches depending on the scales,
      none of which are properly validated today. OBJECTIVE: To create an AB severity
      scale (ABSS) and to validate it. MATERIAL AND METHOD: The development of a
      parameterized construct with a gradual cumulative score of respiratory rate,
      heart rate, respiratory effort, auscultation of wheezing and crackles, and the
      inspiration/expiration ratio. Also, the validation of the ABSS performed on
      patients diagnosed with AB, the reliability measured by observing the behavior of
      internal consistency, test-retest, external validity and inter-observer
      agreement. RESULTS: From a total of 290 measurements a Cronbach's reliability
      alpha of 0.83 was obtained; Kappa agreement index of 0.93 in the test-retest
      agreement, and Kappa index of 0.682 (alpha<0.05) for inter-observer agreement.
      CONCLUSIONS: The ABSS can be a reliable tool for measuring the severity of AB.

PMID- 24103251
TI  - [Neonatal testicular tumour].

PMID- 24103252
TI  - [Complex febrile seizures: study of the associated pathology and practical use of
      complementary tests].
AB  - INTRODUCTION: Although one third of febrile seizures are complex, a consensus has
      still not been reached on how to manage them, as is the case with simple febrile
      seizures. The objective of this study is to estimate the usefulness of
      complementary examinations and the risk of associated serious intracranial
      pathology. PATIENTS AND METHODS: A retrospective review was conducted from 2003
      until 2011 on patients from 6 months to 6 years presenting with a complex febrile
      seizure admitted to a tertiary care hospital, excluding the cases with previous
      neurological disease. Epidemiological and clinic variables were collected, as
      well as complementary tests and complications. RESULTS: We found 65 patients (31
      females and 34 males), of whom 44 had repeated seizures in the first 24 hours,
      with 15 having focal seizures. The vast majority (90%) of the recurrences
      occurred before 15 hours. The mean age was 20.7 months and temperature was 39.1
      +/- 0.12 degrees C. None of the patients had severe intracranial pathology. The
      electroencephalogram gave no helpful information for the diagnosis. Neuroimaging
      was normal in all studied cases. CONCLUSIONS: The incidence of complications in
      complex febrile seizure in our series did not justify the systematic admission or
      the systematic study with complementary tests when the neurological examination
      was normal. The routine electroencephalogram does not appear to be justified.

PMID- 24103253
TI  - Low-methane yield sheep have smaller rumens and shorter rumen retention time.
AB  - In the present study, following the measurement of methane emissions from 160
      mature ewes three times, a subset of twenty ewes was selected for further
      emission and physiological studies. Ewes were selected on the basis of methane
      yield (MY; g CH4/kg DM intake) being low (Low MY: >1 sd below the mean; n 10) or
      high (High MY: >1 sd above the mean; n 10) when fed a blended chaff ration at a
      fixed feeding level (1.2-fold maintenance energy requirements). The difference
      between the Low- and High-MY groups observed at the time of selection was
      maintained (P= 0.001) when remeasured 1-7 months later during digesta kinetics
      studies. Low MY was associated with a shorter mean retention time of particulate
      (P< 0.01) and liquid (P< 0.001) digesta, less amounts of rumen particulate
      contents (P< 0.01) and a smaller rumen volume (P< 0.05), but not apparent DM
      digestibility (P= 0.27) or urinary allantoin excretion (P= 0.89). Computer
      tomography scanning of the sheep's rumens after an overnight fast revealed a
      trend towards the Low-MY sheep having more clearly demarcated rumen gas and
      liquid phases (P= 0.10). These findings indicate that the selection of ruminants
      for low MY may have important consequences for an animal's nutritional
      physiology.

PMID- 24103254
TI  - Pharmacokinetic and pharmacodynamic effects of methylphenidate and MDMA
      administered alone or in combination.
AB  - Methylphenidate and 3,4-methylenedioxymethamphetamine (MDMA, 'ecstasy') are
      widely misused psychoactive drugs. Methylphenidate increases brain dopamine and
      norepinephrine levels by blocking the presynaptic reuptake transporters. MDMA
      releases serotonin, dopamine and norepinephrine through the same transporters.
      Pharmacodynamic interactions of methylphenidate and MDMA are likely. This study
      compared the pharmacodynamic and pharmacokinetic effects of methylphenidate and
      MDMA administered alone or in combination in healthy subjects using a double
      blind, placebo-controlled, crossover design. Methylphenidate did not enhance the
      psychotropic effects of MDMA, although it produced psychostimulant effects on its
      own. The haemodynamic and adverse effects of co-administration of methylphenidate
      and MDMA were significantly higher compared with MDMA or methylphenidate alone.
      Methylphenidate did not change the pharmacokinetics of MDMA and vice versa.
      Methylphenidate and MDMA shared some subjective amphetamine-type effects;
      however, 125 mg of MDMA increased positive mood more than 60 mg of
      methylphenidate, and methylphenidate enhanced activity and concentration more
      than MDMA. Methylphenidate and MDMA differentially altered facial emotion
      recognition. Methylphenidate enhanced the recognition of sad and fearful faces,
      whereas MDMA reduced the recognition of negative emotions. Additionally, the
      present study found acute pharmacodynamic tolerance to MDMA but not
      methylphenidate. In conclusion, the combined use of methylphenidate and MDMA does
      not produce more psychoactive effects compared with either drug alone, but
      potentially enhances cardiovascular and adverse effects. The findings may be of
      clinical importance for assessing the risks of combined psychostimulant misuse.
      Trial registration identification number: NCT01465685
      (http://clinicaltrials.gov/ct2/show/NCT01465685).

PMID- 24103256
TI  - Boundary layer aerosol characteristics at Mahabubnagar during CAIPEEX-IGOC:
      modeling the optical and radiative properties.
AB  - An Integrated Ground Observational Campaign (IGOC) was conducted at Mahabubnagar-
      a tropical rural station in the southern peninsular India, under the Cloud
      Aerosol Interaction and Precipitation Enhancement Experiment (CAIPEEX) program
      during the period from July to November 2011. Measured chemical composition and
      carbonaceous aerosols from PM2.5 samples were used in an aerosol optical model to
      deduce crucial aerosol optical properties, which were then used in a radiative
      transfer model for radiative forcing estimations. The model derived aerosol
      optical depth (AOD at 500 nm), varied from 0.13 to 0.76 (mean of 0.40 +/- 0.18)
      whereas Angstrom exponent (AE) between 0.10 and 0.65 (mean of 0.33 +/- 0.17)
      suggests relative dominance of coarse particles over the station. On the other
      hand, single scattering albedo (SSA at 500 nm) was found to vary from 0.78 to
      0.92 (mean of 0.87 +/- 0.04) during the measurement period. The magnitude of
      absorption Angstrom exponent (AAE), varied from 0.83 to 1.33 (mean of 1.10 +/-
      0.15), suggests mixed type aerosols over the station. Aerosol direct radiative
      forcing was estimated and found to vary from -8.9 to -49.3 W m(-2) (mean of -27.4
      +/- 11.8 W m(-2)) at the surface and +9.7 to +44.5 W m(-2) (mean of +21.3 +/- 9.4
      W m(-2)) in the atmosphere during the course of measurements. The atmospheric
      forcing was observed to be ~30% higher during October (+ 29 +/- 9 W m(-2)) as
      compared to August (+21 +/- 7 W m(-2)) when the station is mostly influenced by
      continental polluted aerosols. The result suggests an additional atmospheric
      heating rate of 0.24 K day(-1) during October, which may be crucial for various
      boundary layer processes in favorable atmospheric conditions.

PMID- 24103255
TI  - The effects of temporally secondary co-morbid mental disorders on the
      associations of DSM-IV ADHD with adverse outcomes in the US National Comorbidity
      Survey Replication Adolescent Supplement (NCS-A).
AB  - BACKGROUND: Although DSM-IV attention deficit hyperactivity disorder (ADHD) is
      known to be associated with numerous adverse outcomes, uncertainties exist about
      how much these associations are mediated temporally by secondary co-morbid
      disorders. METHOD: The US National Comorbidity Survey Replication Adolescent
      Supplement (NCS-A), a national survey of adolescents aged 13-17 years (n = 6483
      adolescent-parent pairs), assessed DSM-IV disorders with the World Health
      Organization (WHO) Composite International Diagnostic Interview (CIDI).
      Statistical decomposition was used to compare direct effects of ADHD with
      indirect effects of ADHD through temporally secondary mental disorders (anxiety,
      mood, disruptive behavior, substance disorders) in predicting poor educational
      performance (suspension, repeating a grade, below-average grades), suicidality
      (ideation, plans, attempts) and parent perceptions of adolescent functioning
      (physical and mental health, interference with role functioning and distress due
      to emotional problems). RESULTS: ADHD had significant gross associations with all
      outcomes. Direct effects of ADHD explained most (51.9-67.6%) of these
      associations with repeating a grade in school, perceived physical and mental
      health (only girls), interference with role functioning and distress, and
      significant components (34.5-44.6%) of the associations with school suspension
      and perceived mental health (only boys). Indirect effects of ADHD on educational
      outcomes were predominantly through disruptive behavior disorders (26.9-52.5%)
      whereas indirect effects on suicidality were predominantly through mood disorders
      (42.8-59.1%). Indirect effects on most other outcomes were through both mood
      (19.8-31.2%) and disruptive behavior (20.1-24.5%) disorders, with anxiety and
      substance disorders less consistently important. Most associations were
      comparable for girls and boys. CONCLUSIONS: Interventions aimed at reducing the
      adverse effects of ADHD might profitably target prevention or treatment of
      temporally secondary co-morbid disorders.

PMID- 24103257
TI  - Ambient organic carbon to elemental carbon ratios: influence of the thermal
      optical temperature protocol and implications.
AB  - Ambient organic carbon (OC) to elemental carbon (EC) ratios are strongly
      associated with not only the radiative forcing due to aerosols but also the
      extent of secondary organic aerosol (SOA) formation. An inter-comparison study
      was conducted based on fine particulate matter samples collected during summer in
      Beijing to investigate the influence of the thermal-optical temperature protocol
      on the OC to EC ratio. Five temperature protocols were used such that the NIOSH
      (National Institute for Occupational Safety and Health) and EUSAAR (European
      Supersites for Atmospheric Aerosol Research) protocols were run by the Sunset
      carbon analyzer while the IMPROVE (the Interagency Monitoring of Protected Visual
      Environments network)-A protocol and two alternative protocols designed based on
      NIOSH and EUSAAR were run by the DRI analyzer. The optical attenuation measured
      by the Sunset carbon analyzer was more easily biased by the shadowing effect,
      whereas total carbon agreed well between the Sunset and DRI analyzers. The
      EC(IMPROVE-A) (EC measured by the IMPROVE-A protocol; similar hereinafter) to
      EC(NIOSH) ratio and the EC(IMPROVE-A) to EC(EUSAAR) ratio averaged 1.36 +/- 0.21
      and 0.91 +/- 0.10, respectively, both of which exhibited little dependence on the
      biomass burning contribution. Though the temperature protocol had substantial
      influence on the OC to EC ratio, the contributions of secondary organic carbon
      (SOC) to OC, which were predicted by the EC-tracer method, did not differ
      significantly among the five protocols. Moreover, the SOC contributions obtained
      in this study were comparable with previous results based on field observation
      (typically between 45 and 65%), but were substantially higher than the estimation
      provided by an air quality model (only 18%). The comparison of SOC and WSOC
      suggests that when using the transmittance charring correction, all of the three
      common protocols (i.e., IMPROVE-A, NIOSH and EUSAAR) could be reliable for the
      estimation of SOC by the EC-tracer method.

PMID- 24103258
TI  - [Tryptase of mast cells in immune organs of developing chicken embryos].
AB  - OBJECTIVE: To observe the form, distribution and emerging time of the mast cells
      (MCs) and tryptase positive cells (TPCs) in the immune organs of different days
      old chicken embryos. METHODS: The thymus, bursa of Fabricius and spleen of
      chicken embryos at different development time were taken and fixed in Carnoy's
      solution. The alcian blue/safranine O (AB/SO) and streptavidin-biotin complex
      (SABC) immunohistochemistry were used to observe the MCs and TPCs. RESULTS: MCs
      were first present in the thymus, bursa and spleen of day 13-14 embryos. The
      number of MCs increased along with the development days. On day 16, TPCs were
      first found in the immune organs. The form and distribution of TPCs were similar
      to MCs, but the emerging time of TPCs was later than that of MCs. CONCLUSION:
      Tryptase appears in the MCs in the immune organs of day 16 or later chicken
      embryos, and it is mainly located in the MCs of the connective tissues.

PMID- 24103259
TI  - [Effect of geniposide on LPS-induced activation of TLR4-NF-kappaB pathway in
      RAW264.7 macrophage cell line].
AB  - OBJECTIVE: To study the anti-inflammatory mechanism of geniposide and observe the
      effect of geniposide on the expression of Toll-like receptor 4 (TLR4), the
      activity of NF-kappaB, and the release of pro-inflammatory cytokines- TNF-alpha,
      IL-1, and IL-6-in the RAW264.7 macrophages treated with lipopolysaccharide (LPS).
      METHODS: There were three experimental groups, including the control group, LPS
      group and LPS combined with geniposide group in this study. RAW264.7 macrophage
      cells were treated with LPS to induce cellular inflammation. Cell proliferation
      was measured by CCK-8. The concentrations of TNF-alpha, IL-1, and IL-6 in cell
      culture media were measured by ELISA. mRNA levels of TLR4 and P65 were examined
      by real-time PCR. The protein levels of p-IkappaB, P65, p-P65 and TLR4 were
      detected by Western blotting. RESULTS: Geniposide had no effect on cell
      proliferation. However, geniposide down-regulated the expression of TNF-alpha, IL
      1, and IL-6, and also inhibited the expression of TLR4 and the activity of NF
      kappaB. CONCLUSION: Geniposide exerts its anti-inflammatory effect through
      inhibiting the activity of NF-kappaB in the TLR4-NF-kappaB pathway in
      macrophages.

PMID- 24103261
TI  - [Anti-inflammatory effect of Syk inhibitor in LPS stimulated macrophages].
AB  - OBJECTIVE: To investigate the role of spleen tyrosine kinase (Syk)on the Toll
      like receptor 4 (TLR4) signal transduction cascade. METHODS: RAW264.7 macrophages
      were treated with different concentrations of Syk inhibitor and then stimulated
      with 100 ng/mL lipopolysaccharide (LPS). The cell viability was tested by the
      Alarmarblue assay. The NO production was detected by Griess reagents and
      cytokines in culture supernatants were quantified by ELISA. The expression of
      iNOS was detected by Western blotting. Moreover, the activation of the
      transcription factors NF-kappaB and activator protein 1 (AP-1) was investigated
      using the reporter cell line RAW-Blue(TM);. RESULTS: The Syk inhibitor had no
      effect on the cell proliferation even at concentrations of 14 MUmol/L. However,
      the NO production (P<0.01) and iNOS expression resulting from LPS stimulation
      were inhibited, when the inhibitor concentration exceeded 1.5 MUmol/L, and the
      TNF-alpha and IL-6 production were inhibited even at lower concentrations
      (P<0.01). Moreover, inhibition of the activation of both the transcription
      factors NF-kappaB and AP-1 was observed. CONCLUSION: The Syk inhibitor shows a
      significant anti-inflammatory property due to its inhibitory effect on NO and
      cytokine production by LPS stimulated macrophages. This effect correlated with
      the reduced activation of both transcription factors NF-kappaB and AP-1, which
      places Syk downstream of the TLR4 signal pathway but upstream of the point of
      divergence of both transcription factors.

PMID- 24103260
TI  - [MicroRNA-10a accelerates endodermal lineage differentiation of mesenchymal stem
      cells from human placenta].
AB  - OBJECTIVE: To improve the potential of endodermal differentiation of human
      placenta-derived mesenchymal stem cells (PMSCs) by microRNA-10a (miR-10a)
      mediated post-transcriptional regulation of its mRNA targets. METHODS: Lentiviral
      vectors were used to stably and specifically over-express miR-10a and inhibited
      the miR-10a function by its antagomir. In addition, the relationship between miR
      10a and Hoxa1 expression was analyzed. Real-time quantitative PCR (qRT-PCR) and
      immunofluorescent cytochemical staining were utilized to test the mRNA and
      protein expression variation and assess the ability of PMSCs to differentiate
      into endodermal cells. Results Over-expression of miR-10a led to the suppression
      of endogenous Hoxa1 expression, and inhibition of miR-10a relieved the repression
      of Hoxa1. Over-expression of miR-10a in PMSCs resulted in the up-regulation of
      endoderm-specific genes (FoxA2, Sox-17, Pdx-1 and Cdx2) and the increased
      proportions of FOXA2, SOX-17 and PDX-1 positive events as compared with the
      control treated cells. CONCLUSION: miR-10a was up-regulated during endodermal
      differentiation of PMSCs and involved in its differentiation partially via the
      suppression of the Hoxa1 gene. Furthermore, the miR-10a accelerates endodermal
      differentiation, likely mediated by the up-reguation of endoderm-specific down
      stream genes.

PMID- 24103262
TI  - [Role of bone marrow-derived mesenchymal stem cells in treating colitis through
      Fas/FasL-mediated immune regulation].
AB  - OBJECTIVE: To investigate the difference in the therapeutic effects of bone
      marrow-derived mesenchymal stem cells (BMSCs) of mice from ovariectomy (OVX)
      group and sham group in treating colitis, and then further study the differences
      of Fas/FasL expression and downstream T cell migration and apoptosis between the
      two groups. METHODS: The osteoporosis animal models were set up by ovariectomy in
      C57BL6 mice. Meanwhile, 3% dextran sulfate sodium (DSS) was administered for
      inducing colitis. We compared the therapeutic effects of BMSCs from OVX and sham
      groups in treating colitis, in addition, detected the expression of Fas/FasL in
      BMSCsby means of RT-PCR and Western blotting. The ability of BMSCs from the two
      groups of inducing T cell migaration and apoptosis was also detected. RESULTS:
      Compared with the sham group, BMSCs from OVX mice expressed a lower level of
      Fas/FasL and displayed a decreased ability of inducing T cell migration and
      apoptosis, thus leading to an inferior therapeutic effect in treating colitis in
      animal models. CONCLUSION: Fas/FasL expression of BMSCs from the OVX mice is down
      regulated, thus leading to a decrease of the migration and apoptosis for T cells
      from mouse colitis.

PMID- 24103263
TI  - [Construction and identification of the eukaryotic expression vector expressing
      short hairpin RNA targeting human COL1A1].
AB  - OBJECTIVE: To construct the eukaryotic expression vector of short hairpin RNA
      (shRNA) targeting human collagen type 1 alpha 1 (COL1A1) and observe its
      inhibiting effect on the expression of target gene. METHODS: The complementary
      oligonucleotide sequences coding shRNA were designed and synthesized according to
      the sequence of human COL1A1 gene, and cloned into the linearized
      pSilencer(TM);2.1-U6 neo vector. The recombinant vector was confirmed by enzyme
      digestion analysis and DNA sequencing, and then the positive clones were
      transfected to human breast cancer cell MDA-MB-231 by Lipofectamine(TM);2000. The
      stable cell line was selected by G418. The expression of COL1A1 gene was detected
      by semi-quantitative RT-PCR and Western blot analysis. RESULTS: Double-enzyme
      digestion and DNA sequencing verified the correct sequences of the recombinant
      plasmid pshRNA-COL1A1. Compared with the control group, the expression level of
      COL1A1 mRNA and protein was inhibited markedly by pshRNA-COL1A1-1 or pshRNA
      COL1A1-2 transfection, and the inhibitory rates were respectively (44.41+/
      3.90)%, (63.05+/-3.13)% in RT-PCR and (45.50+/-2.71)%, (66.98+/-2.08)% in Western
      blot analysis. CONCLUSION: Specific shRNA interference plasmid vector targeting
      COL1A1 gene mRNA was constructed successfully.

PMID- 24103264
TI  - [Protective effect of anhydroicaritin against peritonitis in mice].
AB  - OBJECTIVE: To investigate the effect of anhydroicaritin (AHI) against zymosan
      induced peritonitis in mice. METHODS: Peritonitis was induced in mice by
      intraperitoneal injection of zymosan. All mice were monitored for systemic
      toxicity and mortality for 13 d after zymosan or saline administration. In
      another set of experiments, the peritoneal exudates were collected. The leukocyte
      numbers and the production of inflammatory cytokines (IL-6, IL-10, TNF-alpha, MCP
      1) were determined by flow cytometry. The release of nitric oxide (NO) was
      measured by a Griess reagent system. The Ca(2+); influx in bone marrow-derived
      macrophages was recorded by laser scanning confocal microscopy with Fluo4-AM
      loading. The expression of iNOS was determined by Western blotting. RESULTS: AHI
      (4 mg/kg) prolonged survival of peritonitis mice, inhibited massive leukocyte
      transmigration into the peritoneal cavity, and decreased the overproduction of
      NO, IL-10, TNF-alpha, MCP-1 and IL-6. In LPS-stimulated mouse macrophages, AHI (5
      MUmol/L) pretreatment significantly inhibited the elevation of intracellular
      Ca(2+);, and markedly decreased iNOS protein expression. CONCLUSION: AHI
      possesses significant protective effects on the zymosan-induced peritonitis mice,
      which might be associated with the regulation of Ca(2+); influx in macrophages
      and iNOS expression.

PMID- 24103265
TI  - [Effect of plasmid transfected shMRE11 on the drug-resistance of BEL7402/5-FU
      hepatoma cells].
AB  - OBJECTIVE: To investigate the impact of silencing meiotic recombination 11
      (MRE11) gene by shMRE11 on the chemotherapeutic drug sensitivity and the
      resistance-associated protein (MRP1) expression on the drug-resistant BEL7402/5
      FU hepatoma cells, and to confirm the relationship between MRE11 and drug
      resistance of hepatoma cells. METHODS: shMRE11 was transiently transfected into
      BEL7402/5-FU cells via cathodolyte liposome transfection method. The silencing
      efficiency was evaluated by quantitative real-time PCR (qRT-PCR) and Western
      blotting. MTT assay was used to detect the sensitivity of transfected BEL7402/5
      FU to cisplatin (DDP), mitomycin C (MMC), adriamycin (ADM) and 5-FU. qRT-PCR and
      Western blotting were employed respectively to detect the change in the mRNA and
      protein levels of drug-resistance protein MRP1 in transfected BEL7402/5-FU.
      RESULTS: The qRT-PCR and Western blotting showed that the silencing efficiency of
      MRE11 mRNA and protein was 78.0% and 56.1%, respectively. Compared with the
      control group, IC50; of shMRE11 group treated with DDP, MMC, ADM, 5-FU was
      reduced significantly as shown by MTT assay (P<0.05); qRT-PCR and Western blot
      analysis of MRP1 showed that its expression significantly decreased at the mRNA
      and protein levels (P<0.05). CONCLUSION: shMRE11 can effectively improve the
      sensitivity of BEL7402/5-FU cells to anticancer drugs and down-regulate the
      expression of multidrug resistance associated protein MRP1.

PMID- 24103266
TI  - [Comparison of site-mutated and error-prone PCR methods for constructing the
      secondary phage antibody libraries].
AB  - OBJECTIVE: To compare site-mutated PCR and error-prone PCR methods in
      constructing the secondary phage antibody libraries derived from a primary
      extracellular domain of cell adhesion molecule L1 (L1-ecd) binding single-chain
      variable fragment (scFv) antibody. METHODS: Secondary mutant phage libraries were
      established by transfecting the mutated phage at the DNA level to E.coli TG1 with
      designed site-mutated PCR or error-prone PCR primers. Using the selected phagemid
      as the template, the mutated plasmid was amplified by PCR and then constructed
      with restriction enzyme cutting and ligation. Phage-based ELISA was used to
      calculate the ratios of the positive monoclones from the two libraries and the
      results were statistically compared using the Pearson x(2); method. RESULTS: The
      size of the two libraries were 1.4*10(6); pfu/mL (site-mutated library) and
      2.5*10(6); pfu/mL (error-prone library), respectively. The ratios of positive
      clones were 32.5% and 35.5%, respectively. The P value was 0.67, showing no
      significant difference. CONCLUSION: These two methods can be widely used to
      obtain antibodies with a high affinity on the basis of the existing phage
      antibody.

PMID- 24103267
TI  - [Preparation of monoclonal antibodies against flagellin core protein of Vibrio
      vulnificus and its application in testing Vibrio vulnificus from food products].
AB  - OBJECTIVE: To prepare the monoclonal antibodies (mAbs) against flagellin core
      protein of Vibrio (V.) vulnificus and establish the double-antibody sandwich
      ELISA for testing V. vulnificus from food products. METHODS: BALB/c mice were
      immunized by flagellin which was extracted by differential centrifugation method
      from V. vulnificus ATCC 1.1758. The splenocytes taken from the immunized mice
      were fused with Sp2/0 myeloma cells when the antibody titer reached 1:32 000 in
      serum. The hybridoma cell lines were prepared and screened by hybridoma technique
      and ELISA. The cells secreting mAbs were cloned through the limited dilution. The
      hybridoma cell lines were used to generate ascites. The mAbs were obtained by
      purification from the ascites. RESULTS: Five hybridoma cell lines which stably
      secreted mAbs against flagellin were isolated and named VVNo.1-VVNo.5. The mAb
      titer in serum reached 1:(2*10(6);). SDS-PAGE showed that the relative molecular
      mass (Mr;) of flagellin protein was 44 000, and that the purity was high. Double
      antibody sandwich ELISA was set up using VVNo.5 antibody, and the sensitivity
      reached 10(3); CFU/mL culture broth. The ELISA showed that VVNo.5 antibody was
      highly specific to V. vulnificus. The detection limit was 2 CFU/25 g culture
      broth in artificial contaminated samples. CONCLUSION: The mAbs were obtained
      against flagellin core protein of V. vulnificus. The double-antibody sandwich
      ELISA was established using VVNo.5 mAb. The monoclonal antibody of VVNo.5 was
      highly specific to V. vulnificus, without cross reaction with non-target
      bacteria. Therefore the monoclonal antibodies of VVNo.5 could be widely used in
      detecting V. vulnificus from food samples as well as the clinical samples.

PMID- 24103268
TI  - [Changes and the implications of CD4(+);CD25(+);CD127(low); regulatory T cells in
      drug addicts during natural drug withdrawal].
AB  - OBJECTIVE: To study the changes of CD4(+);CD25(+);CD127(low); regulatory T cells
      (Tregs) and transforming growth factor beta 1 (TGF-beta1) mRNA in peripheral
      blood mononuclear cells (PBMCs) in drug addicts during natural drug withdrawal,
      and explore the effects of addictive drugs on their Tregs. METHODS: Peripheral
      blood was collected from 40 drug addicts with 6-month natural withdrawal, 40
      cases with 18-month natural withdrawal and 30 healthy controls. Then the Tregs
      were counted by flow cytometry and TGF-beta1 mRNA expression in PBMCs was
      detected by RT-PCR. RESULTS: Compared with the controls, Tregs and TGF-beta1 mRNA
      expression in PBMCs increased significantly in the group with one 18-month
      natural withdrawal, but no significant difference was found in the group with 6
      month natural withdrawal. CONCLUSION: Addictive drugs have a long-term effect on
      the Tregs in drug addicts, and the abnormal Tregs may result in the immune
      dysfunction in drug addicts.

PMID- 24103269
TI  - [Prokaryotic expression and immunogenicity analysis of phosphoglycerate kinase 1
      of Candida albicans].
AB  - OBJECTIVE: To construct prokaryotic expression plasmids of Candida albicans gene
      phosphoglycerate kinase 1 (pgk-1) and examine the immunogenicity of the
      recombinant protein. METHODS: The full-length coding sequence of pgk-1 was
      amplified by PCR and cloned into the prokaryotic expression vector pET30a. The
      6*His-tagged protein was induced by IPTG in E.coli BL-21(DE3) and the recombinant
      protein was identified by SDS-PAGE and Western blotting. The BALB/c mice were
      immunized with the purified recombinant protein to evaluate the antigenicity of
      the recombinant protein by ELISA. RESULTS: The full-length pgk-1 gene was cloned
      from SC5314 genome and pET-30a-pgk-1 was successfully constructed. The
      recombinant protein PGK-1 was highly expressed in E.coli with a relative molecule
      mass of 54 810. ELISA indicated that the titer of the antibody was about 1:1024.
      CONCLUSION: PGK-1 was successfully expressed by prokaryotic expression system and
      the recombinant protein showed favorable immunogenicity in mice.

PMID- 24103270
TI  - [Construction and identification of a recombinant replication-defective
      adenovirus vector encoding p53AIP1 and its expression in human HeLa cells].
AB  - OBJECTIVE: To construct a recombinant replication-defective adenovirus vector
      carrying p53AIP1 (p53-regulated apoptosis-inducing protein 1) gene and observe
      its expression in human HeLa cells. METHODS: Specific primers were designed
      according to p53AIP1 gene sequence and inserted specific enzyme cutting sites.
      P53AIP1 gene was amplified by PCR and cloned into the adenovirus shuttle plasmid
      pDC316 to construct the recombinant vector pDC316-p53AIP1, which was co
      transfected with helper plasmid pBHGloxdeltaE1, 3Cre into HEK293 cells by
      Lipofectamine(TM); 2000. The recombinant replication-defective adenovirus (Ad
      p53AIP1) was generated by means of homologous recombination of the two plasmids
      in HEK293 cells with the Cre-loxP recombinase system and harvested after 12 days.
      Ad-p53AIP1 and Ad-null were respectively transfected into HeLa cells at MOI=100.
      Then the expression of p53AIP1 gene was detected by Western blotting. RESULTS:
      pDC316-p53AIP1 was constructed successfully. The new constructed vector was
      confirmed by PCR analysis, double enzyme digestion and DNA sequencing. The
      results were in conformity with the expected. Western blotting demonstrated that
      the target p53AIP1 proteins were effectively expressed in the transfected HeLa
      cells. CONCLUSION: The recombinant adenovirus vector of Ad-p53AIP1 was
      successfully established, and it was proved to have a strong ability of
      infectivity.

PMID- 24103271
TI  - [Primary culture and multiple differentiation potency of mesenchymal stem cells
      from human umbilical cord].
AB  - OBJECTIVE: To establish a reliable method of isolation, culture and
      characterization of human umbilical cord-derived mesenchymal stem cells (hUCMSCs)
      and study its multiple differentiation potency. METHODS: HUCMSCs were isolated
      and cultured using Trypsin-type II collagen and hyaluronidase digestion method
      and tissue explant culture method, respectively. The cell growth of hUCMSCs was
      observed under an inverted microscope. Cell viability rate of the different
      passages was evaluated by trypan blue staining. The proliferation profile of
      hUCMSCs was analyzed by growth curve and MTT assay. Flow cytometry was used to
      study the cell cycle and immunophenotypage change. The differentiation potency of
      hUCMSCs towards the osteoblasts, adipocytes was assayed using the differentiation
      kits. The differentiation towards the cardiomyocytes and endothelial cells was
      tested by immunofluoresence staining with the specific markers. RESULTS: After 1
      day culture of the enzyme digested cells, under the inverted microscope, the
      adherent cells were round, and 4 days later, they grew quickly and presented
      fusiform. Seven days later, the cells proliferated from the center to the
      peripheral and fused by 80% on day 10. With the tissue explant culture method,
      the cells started to proliferate gradually from the periphery of the tissue and
      grew quickly and arrayed closely in monolayer after 10 days. The cell viability
      in both isolation methods were more than 96% as tested by trypan blue staining.
      The growth curve of the third passage presented an "S" shape. MTT assay showed
      that the optimal cell proliferation occured on day 3 to 5. The ratios of G0/G1
      phase and S+G2/M phase was 88.78% and 10.21% respectively by enzyme digestion,
      and 84.82% and 13.87% respectively by explant culture method. There was no
      significant difference in cell cycle. The positive rates of CD90, CD105, CD73
      were more than 99% and the expressions of CD45, CD34, CD14, CD11b, CD79a, CD19,
      HLA-DR were lower than 1%. The hUCMSCs isolated by the two methods could
      efficiently differentiate towards the osteoblasts, lipocytes, cardiac myocytes
      and endothelial cells, and the positive rates were all above 90%. CONCLUSION: The
      hUCMSCs can be effectively isolated by both enzyme digestion and explant culture
      methods. The enzyme isolation method presents a better method regarding the cell
      number obtained. This study showed the enzyme isolation method may be an optimal
      method to isolate the hUCMSCs for the cellular therapy and stem cell
      bioengineering.

PMID- 24103272
TI  - [The stability of synthesized EGFP mRNA in vitro transfected into human umbilical
      cord mesenchymal stem cells].
AB  - OBJECTIVE: To identify human umbilical cord mesenchymal stem cells (hUCMSCs) and
      increase the stability of the in vitro synthesized EGFP mRNA through
      modification. METHODS: Immunophenotype of hUCMSCs was examined by flow cytometry.
      Adipogenic and osteogenic differentiations were determined by oil red O and
      alkaline phosphatase staining, respectively. In vitro synthesized EGFP mRNA was
      modified through polyA tailing, capping and adding base analogues, and then
      transfected into the hUCMSCs. After transfection, the fluorescence intensity was
      detected by flow cytometry and cell viability was determined by Trypan blue
      staining. RESULTS: Flow cytometry revealed that the hUCMSCs were positive for
      CD29, CD44, CD105, and were negative for CD34, CD45 and HLA-DR. They had the
      capacity of differentiating into adipocytes and osteoblasts. Through the
      modification the in vitro synthesized mRNA was more stable than unmodified mRNA,
      and mRNA transfection had lower cytotoxicity than DNA. CONCLUSION: Modification
      can highly improve the stability of in vitro synthesized mRNA, which can be
      translated into protein in hUCMSCs.

PMID- 24103273
TI  - [Screening of short peptides that bind specifically to ovarian cancer cell line
      through whole-cell subtraction biopanning].
AB  - OBJECTIVE: To obtain short peptides that bind specifically to ovarian carcinoma
      cell line HO8910 by whole-cell subtraction biopanning as an ideal vector for
      targeted drug delivery in ovarian cancer therapy. METHODS: With the HO8910
      ovarian carcinoma cells as the target cells and human normal ovarian epithelial
      cells as the adherent cells, 4 rounds of panning from a PH.D-C7C phage-display
      peptide library were carried out. Individual phage clones were selected and
      identified by ELISA. Positive phage clones were characterized with DNA sequencing
      and bioinformatics analysis. The specific binding of the positive phage clones to
      HO8910 cells was tested with immunofluorescence cytochemistry. RESULTS: After 4
      rounds of biopanning, phage clones showed preferential binding to the target
      cells. ELISA identified 12 positve phage clones from 20 randomly selected ones.
      Heptapentide (SWQIGGN) that bound specifically to ovarian cancer cells was
      obtained by DNA sequencing. The results of immunofluorescence cytochemistry
      indicated that phage1 could be specifically bound to HO8910 cells. CONCLUSION: By
      means of whole-cell subtraction biopanning, we found a novel heptapentide which
      was able to bind specifically to ovarian cancer cells.

PMID- 24103274
TI  - Diagnostic accuracy of K-ras mutation for pancreatic carcinoma: a meta-analysis.
AB  - BACKGROUND: The conventional tests for the diagnosis of early stage pancreatic
      carcinoma are not acceptable. This meta-analysis is to evaluate the accuracy of K
      ras mutation for the diagnosis of pancreatic carcinoma. DATA SOURCES: A systemic
      search of all relevant literature was performed in Web of Science, EMBASE,
      Cochrane Database, and MEDLINE (PubMed as the search engine) prior to June 1,
      2011. Thirty-four studies fulfilled the inclusion criteria and data were pooled
      for analysis. RESULTS: The pooled estimates for K-ras mutation in diagnosis of
      pancreatic carcinoma were as follows: sensitivity 0.68 (95% CI: 0.66-0.71),
      specificity 0.87 (95% CI: 0.85-0.88), positive likelihood ratio 4.54 (95% CI:
      3.47-5.94), negative likelihood ratio 0.37 (95% CI: 0.30-0.44) and diagnostic
      odds ratio 14.90 (95% CI: 10.02-22.15). Summary receiver operating characteristic
      analysis demonstrated that the maximum joint sensitivity and specificity was
      0.79, and the overall area under the curve was 0.86. CONCLUSIONS: Diagnostic
      accuracy of K-ras mutation was not superior to that of conventional tests.
      Therefore, K-ras mutation analysis alone is not recommended for the diagnosis of
      pancreatic carcinoma.

PMID- 24103275
TI  - Prevention of recurrent hepatitis B infection after liver transplantation.
AB  - BACKGROUND: Recurrence of hepatitis B virus (HBV) infection after liver
      transplantation can lead to graft loss and a reduction in long-term survival. The
      purpose of this review is to summarize the current therapeutic options for
      preventing HBV recurrence in liver transplant recipients. DATA SOURCES: Up to
      January 2013, studies that were published in MEDLINE and EMBASE on prevention of
      HBV recurrence after liver transplantation were reviewed. RESULTS: There have
      been remarkable advancements in the past two decades on the prevention of HBV
      recurrence after liver transplantation, from the discovery of hepatitis B immune
      globulin (HBIG) and lamivudine monotherapy to the combination therapy using HBIG
      and lamivudine. With the development of newer and stronger antiviral agents, the
      need for life-long HBIG is doubtful. With their low resistance profile, oral
      antiviral prophylaxis using these new agents alone is sufficient and is
      associated with excellent outcome. CONCLUSIONS: Restoration of host HBV immunity
      with adoptive immunity transfer and vaccination may represent the ultimate
      strategy to withdraw prophylactic treatment and to achieve a drug free regimen
      against HBV recurrence after liver transplantation.

PMID- 24103276
TI  - Risk assessment in patients undergoing liver resection.
AB  - BACKGROUND: Liver resection is still a risky procedure with high morbidity and
      mortality. It is significant to predict the morbidity and mortality with some
      models after liver resection. DATA SOURCES: The MEDLINE/PubMed, Web of Science,
      Google Scholar, and Cochrane Library databases were searched using the terms
      "hepatectomy" and "risk assessment" for relevant studies before August 2012.
      Papers published in English were included. RESULTS: Thirty-four original papers
      were included finally. Some models, such as MELD, APACHE II, E-PASS, or POSSUM,
      widely used in other populations, are useful to predict the morbidity and
      mortality after liver resection. Some special models for liver resection are used
      to predict outcomes after liver resection, such as mortality, liver dysfunction,
      transfusion, or acute renal failure. However, there is no good scoring system to
      predict or classify surgical complications because of shortage of internal or
      external validation. CONCLUSION: It is important to validate the models for the
      major complications after liver resection with further internal or external
      databases.

PMID- 24103277
TI  - The diversity between pancreatic head and body/tail cancers: clinical parameters
      and in vitro models.
AB  - BACKGROUND: Pancreatic ductal adenocarcinoma (PDAC) can be divided into head,
      body and tail cancers according to the anatomy. Distinctions in tissue
      composition, vascularization and innervations have been clearly identified
      between the head and body/tail of the pancreas both in embryological development
      and in histopathology. To understand the postulated genotype difference, we
      present comprehensive information on two PDAC cell lines as typical
      representatives originating from pancreatic head and body/tail cancers,
      respectively. DATA SOURCE: In the present review, we compare the difference
      between pancreatic head and body/tail cancers regarding clinical parameters and
      introducing an in vitro model. RESULTS: Increasing evidence has shown that tumors
      at different locations (head vs body/tail) display different clinical
      presentation (e.g. incidence, symptom), treatment efficiency (e.g. surgery,
      chemotherapy) and thus patient prognosis. However, the genetic or molecular
      diversity (e.g. mutations, microRNA) between the two subtypes of PDAC has not
      been elucidated so far. They present different chemo- and/or radio-resistance,
      extracellular matrix adhesion and invasiveness, as well as genetic profiles.
      CONCLUSION: Genetic and tumor biological diversity exists in PDAC according to
      the tumor localization.

PMID- 24103278
TI  - Response to endoscopic therapy for biliary anastomotic strictures in deceased
      versus living donor liver transplantation.
AB  - BACKGROUND: Endoscopic therapy has been successful in the management of biliary
      complications after both deceased donor liver transplantation (DDLT) and living
      donor liver transplantation (LDLT). LDLT is thought to be associated with higher
      rates of biliary complications, but there are few studies comparing the success
      of endoscopic management of anastomotic strictures between the two groups. This
      study aims to compare our experience in the endoscopic management of anastomotic
      strictures in DDLT versus LDLT. METHODS: This is a retrospective database review
      of all liver transplant patients undergoing endoscopic retrograde
      cholangiopancreatography (ERCP) after liver transplantation. The frequency of
      anastomotic stricture and the time to develop and to resolve anastomotic
      stricture were compared between DDLT and LDLT. The response of anastomotic
      stricture to endoscopic therapy was also analyzed. RESULTS: A total of 362
      patients underwent liver transplantation between 2003 and 2011, with 125
      requiring ERCP to manage biliary complications. Thirty-three (9.9%) cases of DDLT
      and 8 (27.6%) of LDLT (P=0.01) were found to have anastomotic stricture. When
      comparing DDLT and LDLT, there was no difference in the mean time to the
      development of anastomotic strictures (98+/-17 vs 172+/-65 days, P=0.11),
      likelihood of response to ERCP [22 (66.7%) vs 6 (75.0%), P=0.69], mean time to
      the resolution of anastomotic strictures (268+/-77 vs 125+/-37 days, P=0.34), and
      the number of ERCPs required to achieve resolution (3.9+/-0.4 vs 4.7+/-0.9,
      P=0.38). CONCLUSIONS: Endoscopic therapy is effective in the majority of biliary
      complications relating to liver transplantation. Anastomotic strictures occur
      more frequently in LDLT compared with DDLT, with equivalent endoscopic treatment
      response and outcomes for both groups.

PMID- 24103279
TI  - Comparison of hepatitis B prophylactic outcomes in living donor liver
      transplantation recipients who meet the Milan or UCSF criteria.
AB  - BACKGROUND: The tumor burden before liver transplantation indicates that
      hepatitis B virus (HBV) may hide in the extrahepatic and micrometastatic sites
      which serve as a source of HBV replication. Currently, many liver transplant
      centers, especially in Western countries, use the Milan or UCSF criteria to
      select patients with hepatocellular carcinoma for liver transplantation. This
      study was undertaken to compare the HBV prophylactic outcomes in two groups of
      living donor liver transplantation (LDLT) recipients. Patients in group A met the
      Milan criteria and those in group B exceeded the Milan criteria but were within
      the UCSF criteria. METHODS: A database of adult-to-adult right-lobe LDLT
      performed at our institution for HBV-related hepatocellular carcinoma within the
      Milan or UCSF criteria between June 2002 and May 2012 was used to compare the HBV
      prophylactic outcomes between patients within the Milan criteria (group A, 41
      patients) and those exceeding the Milan criteria but within the UCSF criteria
      (group B, 19 patients). RESULTS: The 1-, 3-, and 5-year survival rates were
      similar between groups A and B (87.8%, 85.1% and 74.0% vs 73.3%, 61.1% and 61.1%,
      respectively, P=0.067). HBV recurred in 1 patient in 3.1 months after LDLT in
      group A and in 2 patients in group B (1 in 11.9 months and 1 in 24.1 months after
      LDLT). The 1-, 3-, and 5-year HBV recurrence rates were 2.6%, 2.6% and 2.6% in
      group A, and 7.3%, 17.9% and 17.9% in group B, respectively (P=0.118).
      CONCLUSION: LDLT recipients who exceed the Milan criteria but remain within the
      UCSF criteria may have post-transplant HBV prophylactic outcomes similar to those
      who meet the Milan criteria.

PMID- 24103280
TI  - Diagnostic accuracy of enhanced liver fibrosis test to assess liver fibrosis in
      patients with chronic hepatitis C.
AB  - BACKGROUND: The prognosis and clinical management of patients with chronic liver
      diseases are closely related to the severity of liver fibrosis. Liver biopsy is
      considered the gold standard for the staging of liver fibrosis. However, it is an
      invasive test sometimes related to complications. This study aimed to assess the
      diagnostic value of enhanced liver fibrosis (ELF) test to predict liver fibrosis
      in patients with chronic hepatitis C. METHODS: This study included 162 patients
      with liver disease and 67 healthy controls. Hyaluronic acid, tissue inhibitor of
      matrix metalloproteinase type 1, and amino-terminal propeptide type III
      procollagen were measured by enzyme-linked immunosorbent assay with the ELF test
      ADVIA Centaur(r) (Siemens Healthcare Diagnostics Inc.). Fibrosis stage was
      determined using the Metavir scoring system. RESULTS: In our study, for the
      diagnosis of significant fibrosis (Metavir F>=2) a cut-off value >7.72 provides a
      sensitivity of 93.0% and a specificity of 83.0%. The areas under the receiver
      operator characteristic curve, sensitivity, specificity, and positive and
      negative predictive values were 0.94, 93.3%, 81.0%, 93.3%, and 81.0%,
      respectively (P<0.001). For the diagnosis of cirrhosis (Metavir F=4) a cut-off
      value >9.3 provides a sensitivity of 93.0% and a specificity of 86.0%. The areas
      under the receiver operator characteristic curve, sensitivity, specificity, and
      positive and negative predictive values were 0.94, 79.1%, 90.8%, 75.6%, and
      92.3%, respectively (P<0.001). CONCLUSIONS: The ELF test is a promising non
      invasive method for assessing liver fibrosis in patients with chronic hepatitis
      C. It is effective in the diagnosis of both fibrosis and cirrhosis.

PMID- 24103281
TI  - Fine needle aspirating and cutting is superior to Tru-cut core needle in liver
      biopsy.
AB  - BACKGROUND: Liver biopsy is the "gold standard" for evaluating liver disorders,
      but controversies over the potential risk of complications and patient discomfort
      still exist. Using a 21G fine needle, we developed a new biopsy procedure, fine
      needle aspirating and cutting (FNAC). Our procedure obtains enough tissue for
      pathological examination and meanwhile, reduces the risk of biopsy complications.
      The present study was to determine the safety and efficiency of 21G FNAC compared
      with 18G Tru-cut core needle (TCN) in liver tumor biopsies. METHODS: Ninety-four
      patients with unresectable malignant tumors were included in this study. Patients
      were divided into 2 groups: 18G TCN and 21G FNAC. The total positive rate (TPR)
      and safety of both groups were compared. RESULTS: TPR was not different between
      the two groups. Liver puncture track subcapsular hemorrhage and arteriovenous
      shunt were reported with 18G TCN but not with 21G FNAC. The incidence of pain
      caused by biopsy was higher for the 18G TCN group compared to the 21G FNAC group
      (P<0.05). About 82.6% of the patients in the 18G TCN group had a sample length
      >0.5 cm, but 52.1% in the 21G FNAC group (P<0.05). More than 50% of patients in
      both groups had sufficient tissue for immunohistochemical examination.
      CONCLUSIONS: TPR is not different between the 21G FNAC and 18G TCN biopsy
      procedures, but the safety of 21G FNAC is superior to that of 18G TCN. Tissues
      obtained by either of these two procedures are sufficient for a pathological
      diagnosis.

PMID- 24103282
TI  - Risk factors and clinical characteristics of portal vein thrombosis after
      splenectomy in patients with liver cirrhosis.
AB  - BACKGROUND: Portal vein thrombosis (PVT) is a potential lethal complication and
      may have negative influence on the prognosis after splenectomy in patients with
      liver cirrhosis. Prevention and timely detection of PVT are quite significant.
      There is a lack of knowledge about the clinical features and risk factors of PVT.
      Our study aimed to investigate the risk factors and clinical characteristics of
      PVT in order to figure out the high-risk individuals. METHODS: We collected the
      clinical data of 472 consecutive patients with non-neoplastic liver cirrhosis who
      had undergone splenectomy from January 2008 to December 2010 in our institution.
      Clinical and surgical characteristics of patients who developed PVT
      postoperatively and those who did not develop PVT were compared. Univariate and
      multivariate analyses of risk factors of PVT were performed. The mortality and
      rebleeding rate of the patients were also evaluated. RESULTS: Of the 472
      patients, 52 were excluded from the study. PVT developed in 71 (71/420, 16.9%)
      patients. Multivariate analysis revealed that wider preoperative portal vein
      diameter, postoperative thrombocytosis, prolonged prothrombin time and
      periesophagogastric devascularization were significantly correlated with PVT
      development [odds ratio (OR): 5.701, 2.807, 1.850 and 2.090, respectively]. The
      incidence of PVT in patients who took antiplatelet drugs was not lower than that
      in those who did not. Follow-up showed that patients in the PVT group had a
      tendency towards reduced overall survival but it was not statistically
      significant. Gastrointestinal bleeding occurred more often in the PVT group than
      that in the non-PVT group (P=0.044). CONCLUSIONS: Wider preoperative portal vein
      diameter, postoperative thrombocytosis, prolonged prothrombin time and
      periesophagogastric devascularization are independent risk factors of PVT. PVT is
      related with higher risk of postoperative gastrointestinal hemorrhage but has no
      significant impact on the overall survival.

PMID- 24103283
TI  - Optimal central venous pressure during partial hepatectomy for hepatocellular
      carcinoma.
AB  - BACKGROUND: Low central venous pressure (CVP) affects hemodynamic stability and
      tissue perfusion. This prospective study aimed to evaluate the optimal CVP during
      partial hepatectomy for hepatocellular carcinoma (HCC). METHODS: Ninety-seven
      patients who underwent partial hepatectomy for HCC had their CVP controlled at a
      level of 0 to 5 mmHg during hepatic parenchymal transection. The systolic blood
      pressure (SBP) was maintained, if possible, at 90 mmHg or higher. Hepatitis B
      surface antigen was positive in 90 patients (92.8%) and cirrhosis in 84 patients
      (86.6%). Pringle maneuver was used routinely in these patients with clamp/unclamp
      cycles of 15/5 minutes. The average clamp time was 21.4+/-8.0 minutes. These
      patients were divided into 5 groups based on the CVP: group A: 0-1 mmHg; B: 1.1-2
      mmHg; C: 2.1-3 mmHg; D: 3.1-4 mmHg and E: 4.1-5 mmHg. The blood loss per
      transection area during hepatic parenchymal transection and the arterial blood
      gas before and after liver transection were analyzed. RESULTS: With active fluid
      load, a constant SBP >=90 mmHg which was considered as optimal was maintained in
      18.6% in group A (95% CI: 10.8%-26.3%); 39.2% in group B (95% CI: 29.5%-48.9%);
      72.2% in group C (95% CI: 63.2%-81.1%); 89.7% in group D (95% CI: 83.6%-95.7%);
      and 100% in group E (95% CI: 100%-100%). The blood loss per transection area
      during hepatic parenchymal transection decreased with a decrease in CVP. Compared
      to groups D and E, blood loss in groups A, B and C was significantly less
      (analysis of variance test, P<0.05). Compared with the baseline, the blood
      oxygenation decreased significantly when the CVP was reduced. Base excess and
      HCO3- in groups A and B were significantly decreased compared with those in
      groups C, D and E (P<0.05). CONCLUSION: In consideration of blood loss, SBP, base
      excess and HCO3-, a CVP of 2.1-3 mmHg was optimal in patients undergoing partial
      hepatectomy for HCC.

PMID- 24103284
TI  - Simultaneous recovery of dual pathways for ammonia metabolism do not improve
      further detoxification of ammonia in HepG2 cells.
AB  - BACKGROUND: Key enzyme deficiency in the dual-pathway of ammonia metabolism leads
      to low detoxification capacity of HepG2 cells. Previously, we established a
      HepG2/AFhGS cell line with overexpression of human glutamine synthetase (hGS) in
      pathway 1 and a HepG2/(hArgI+hOTC)4 cell line with overexpression of human
      arginase I (hArgI) and human ornithine transcarbamylase (hOTC) in pathway 2. The
      present study aimed to investigate whether simultaneous recovery of the two
      pathways contributes to the further improvement of ammonia detoxification in
      HepG2 cells. METHODS: We adopted a recombinant retrovirus carrying the hGS gene
      to infect HepG2/(hArgI+hOTC)4 cells and selected a new recombinant HepG2 cell
      line. The capacities of ammonia tolerance and detoxification in cells were
      detected by biochemical methods. Cell cycle PCR chip was used to assess the
      changes of gene expression. RESULTS: Introducing hGS into HepG2/(hArgI+hOTC)4
      cells did not lead to hGS overexpression, but inhibited hArgI expression. The
      levels of synthetic glutamine and urea in HepG2/(hArgI+hOTC+AFhGS)1 cells were
      significantly lower than those in HepG2/(hArgI+hOTC)4 cells when cultured in the
      medium with 10 and 15 mmol/L glutamate (Glu) and with 60 and 180 mmol/L NH4Cl,
      respectively. In addition, the comparison of different cell growth showed that
      HepG2/AFhGS cells significantly lagged behind the other cells by the 5th and 7th
      day, indicating that introduction of hGS impedes HepG2 cell proliferation.
      Analysis of the mechanism suggested that the decreased expression of BCL2 played
      an important role. CONCLUSIONS: This study demonstrated that the recovery of two
      ammonia metabolic pathways in HepG2 cells is not helpful in increasing ammonia
      metabolism. The reinforcement of the pathway of urea metabolism is more important
      and valuable in improving the ammonia metabolism capacity in HepG2 cells.

PMID- 24103285
TI  - Clinical and economic consequences of pancreatic fistula after elective
      pancreatic resection.
AB  - BACKGROUND: Postoperative pancreatic fistula is the main cause of morbidity after
      pancreatic resection. This study aimed to quantify the clinical and economic
      consequences of pancreatic fistula in a medium-volume pancreatic surgery center.
      METHODS: Hospital records from patients who had undergone elective pancreatic
      resection in our department were identified. Pancreatic fistula was defined
      according to the International Study Group on Pancreatic Fistula (ISGPF). The
      consequences of pancreatic fistula were determined by treatment cost, hospital
      stay, and out-patient follow-up until the pancreatic fistula was completely
      healed. All costs of the treatment are calculated in Euros. The cost increase
      index was calculated for pancreatic fistula of grades A, B, and C as multiples of
      the total cost for the no fistula group. RESULTS: In 54 months, 102 patients
      underwent elective pancreatic resections. Forty patients (39.2%) developed
      pancreatic fistula, and 54 patients (52.9%) had one or more complications. The
      median length of hospital stay for the no fistula, grades A, B, and C fistula
      groups was 12.5, 14, 20, and 59 days, respectively. The hospital stay of patients
      with fistula of grades B and C was significantly longer than that of patients
      with no fistula (P<0.001). The median total cost of the treatment was 4952, 4679,
      8239, and 30 820 Euros in the no fistula, grades A, B, and C fistula groups,
      respectively. CONCLUSIONS: The grading recommended by the ISGPF is useful for
      comparing the clinical severity of fistula and for analyzing the clinical and
      economic consequences of pancreatic fistula. Pancreatic fistula prolongs the
      hospital stay and increases the cost of treatment in proportion to the severity
      of the fistula.

PMID- 24103286
TI  - Overexpression of IQGAP1 in human pancreatic cancer.
AB  - BACKGROUND: Pancreatic cancer is a highly aggressive malignant tumor with the
      lowest survival rate. A better understanding of the molecular mechanisms which
      contribute to pancreatic cancer occurrence and progression will aid in the
      development of new approaches to the early diagnosis, prevention, and treatment
      of this deadly disease. The scaffold protein IQGAP1 shows elevated levels in a
      variety of cancer types. Currently, we investigated whether or not IQGAP1 is also
      overexpressed in pancreatic cancer. METHODS: IQGAP1 expression was examined in
      pancreatic cancer and normal tissues adjacent to cancerous tissues (adjacent
      tissues) by Western blotting and real-time RT-PCR as well as in paraffin sections
      of tissue microarray by immunohistochemistry. The correlations between IQGAP1
      expression and various clinicopathological characteristics were analyzed.
      RESULTS: Western blotting and real-time RT-PCR revealed that the levels of IQGAP1
      protein and mRNA expression in pancreatic cancer tissues were significantly
      increased compared with adjacent tissues. Immunohistochemistry analysis on tissue
      microarray showed that IQGAP1 protein expression was significantly higher in
      pancreatic cancer (80.0%, 48/60) compared with adjacent tissues (18.3%, 11/60)
      (P<0.001). Moreover, overexpression of IQGAP1 was shown to be associated with the
      grades of tumor differentiation (P<0.05). CONCLUSION: The overexpression of
      IQGAP1 may play an important role in pancreatic cancer occurrence and
      progression, and IQGAP1 may serve as a novel molecular target for the diagnosis
      and treatment of pancreatic cancer.

PMID- 24103287
TI  - The relationship between multiple clinicopathological features and nerve invasion
      in pancreatic cancer.
AB  - BACKGROUND: Nerve invasion is a specific type of tumor expansion and
      characteristic manifestation of pancreatic cancer (PC), with an incidence rate
      ranging from 50% to 100%. It is an important prognostic factor for pancreatic
      cancer, and its early detection is helpful in the management of the disease. This
      study was undertaken to analyze retrospectively the relationship between neural
      invasion and multiple clinicopathological features and to provide evidences for
      clinicians in the management of neural invasion in patients with PC. METHODS:
      Formalin-fixed paraffin-embeded specimens of PC taken from 215 patients were
      examined for the presence of neural invasion under a light microscope. Analyzed
      was the relationship between neural invasion and multiple clinicopathological
      feature including preoperative fasting blood glucose level, amylase level, serum
      CA19-9 level, abdominal pain, lumbar and back pain, and the expressions of p53
      and Ki67 in tumor tissues. RESULTS: Preoperative fasting blood glucose level,
      serum CA19-9 level and p53 positive cells in cancer tissue were increased with
      the rise of pathological grade (P<0.05). These indices were significantly higher
      in patients with neural invasion than in those without (P<0.05). Further analysis
      revealed a positive correlation between p53 and Ki67 overexpression and lymphatic
      metastasis (P<0.05). Referred pain was positively correlated with neural invasion
      (P<0.05). Patients with PC perineural invasion were more likely to have a higher
      pathological grade (P<0.05). CONCLUSIONS: Our data indicated that the
      preoperative fasting blood glucose level, serum CA19-9 level, and referred pain
      are novel predictive markers for neural invasion in patients with PC. p53 and
      Ki67 play important roles in neural invasion of PC. Management of hyperglycemia
      may serve as an auxiliary treatment to curb neural invasion in PC.

PMID- 24103288
TI  - Retrohepatic vena cava deroofing in living donor liver transplantation for
      caudate hepatocellular carcinoma.
AB  - The removal of tumor together with the native liver in living donor liver
      transplantation for hepatocellular carcinoma is challenged by a very close
      resection margin if the tumor abuts the inferior vena cava. This is in contrast
      to typical deceased donor liver transplantation where the entire retrohepatic
      inferior vena cava is included in total hepatectomy. Here we report a case of
      deroofing the retrohepatic vena cava in living donor liver transplantation for
      caudate hepatocellular carcinoma. In order to ensure clear resection margins, the
      anterior portion of the inferior vena cava was included. The right liver graft
      was inset into a Dacron vascular graft on the back table and the composite graft
      was then implanted to the recipient inferior vena cava. Using this technique, we
      observed the no-touch technique in tumor removal, hence minimizing the chance of
      positive resection margin as well as the chance of shedding of tumor cells during
      manipulation in operation. 

PMID- 24103289
TI  - Mattress sutures for the modification of end-to-end dunking
      pancreaticojejunostomy.
AB  - Despite the improvement of surgical techniques, the rate of anastomotic failure
      of pancreaticojejunostomy remains high (30%-50%). Here we describe the use of
      vertical mattress sutures in the modification of dunking pancreaticojejunal
      anastomosis. In 7 patients who used this technique, neither anastomotic failure
      nor any major postsurgical complication developed. This technique is an easy,
      safe, and promising for the performance of pancreaticojejunostomy. 

PMID- 24103290
TI  - The effects of improving hospital physicians working conditions on patient care:
      a prospective, controlled intervention study.
AB  - BACKGROUND: Physicians, particularly in hospitals, suffer from adverse working
      conditions. There is a close link between physicians' psychosocial work
      environment and the quality of the work they deliver. Our study aimed to explore
      whether a participatory work-design intervention involving hospital physicians is
      effective in improving working conditions and quality of patient care. METHODS: A
      prospective, controlled intervention study was conducted in two surgical and two
      internal departments. Participants were 57 hospital physicians and 1581
      inpatients. The intervention was a structured, participatory intervention based
      on continuous group meetings. Physicians actively analyzed problematic working
      conditions, developed solutions, and initiated their implementation. Physicians'
      working conditions and patients' perceived quality of care were outcome criteria.
      These variables were assessed by standardized questionnaires. Additional data on
      implementation status were gathered through interviews. RESULTS: Over the course
      of ten months, several work-related problems were identified, categorized, and
      ten solutions were implemented. Post-intervention, physicians in the intervention
      departments reported substantially less conflicting demands and enhanced quality
      of cooperation with patients' relatives, compared to control group physicians.
      Moreover, positive changes in enhanced colleague support could be attributed to
      the intervention. Regarding patient reports of care quality of care, patient
      ratings of physicians organization of care improved for physicians in the
      intervention group. Five interviews with involved physicians confirm the
      plausibility of obtained results, provide information on implementation status
      and sustainability of the solutions, and highlight process-related factors for re
      design interventions to improve hospital physicians work. CONCLUSIONS: This study
      demonstrates that participatory work design for hospital physicians is a
      promising intervention for improving working conditions and promoting patient
      quality of care.

PMID- 24103291
TI  - [Response to "Commentaries about the supplement "Scientific presentations and
      publications in Radiology: keys and advice for preparation""].

PMID- 24103292
TI  - UHPLC determination of catechins for the quality control of green tea.
AB  - An ultra-high performance liquid chromatography (UHPLC) with UV detection method
      was developed for the fast quantitation of the most represented and biologically
      important green tea catechins and caffeine. UHPLC system was equipped with C18
      analytical column (50mm*2.1mm, 1.8MUm), utilizing a mobile phase composed of pH
      2.5 triethanolamine phosphate buffer (0.1M) and acetonitrile in a gradient
      elution mode; under these conditions six major catechins and caffeine were
      separated in a 3min run. The method was fully validated in terms of precision,
      detection and quantification limits, linearity, accuracy, and it was applied to
      the identification and quantification of catechins and caffeine present in green
      tea infusions. In particular, commercially available green tea leaves samples of
      different geographical origin (Sencha, Ceylon Green and Lung Ching) were used for
      infusion preparations (water at 85 degrees C for 15min). The selectivity of the
      developed UHPLC method was confirmed by comparison with UHPLC-MS/MS analysis. The
      recovery of the main six catechins and caffeine on the three analyzed commercial
      tea samples ranged from 94 to 108% (n=3). Limits of detection (LOD) were
      comprised in the range 0.1-0.4MUgmL(-1). An orthogonal micellar electrokinetic
      (MEKC) method was applied for comparative purposes on selectivity and
      quantitative data. The combined use of the results obtained by the two techniques
      allowed for a fast confirmation on quantitative characterization of commercial
      samples. 

PMID- 24103293
TI  - Amputations and foot-related hospitalisations disproportionately affect dialysis
      patients.
AB  - Patients with diabetes have increased risk for foot ulcers, amputations and
      hospitalisations. We evaluated a closed cohort of patients with diabetes and
      established risk factors in two high risk groups: (i) dialysis patients and (ii)
      patients with previous foot ulceration. We used claims data for diabetes (ICD-9
      250.X), ulceration (ICD-9 707.10, 707.14 and 707.15) and dialysis (CPT 90935
      90937) from the Scott and White Health Plan to identify 150 consecutive patients
      with diabetes on dialysis (dialysis group) and 150 patients with a history of
      foot ulceration (ulcer history group). We verified these diagnoses by manually
      reviewing corresponding electronic medical records. Each patient was provided 30
      months follow-up period. The incidence of foot ulcers was the same in dialysis
      patients and patients with an ulcer history (210 per 1000 person-years). The
      amputation incidence rate was higher in dialysis patients (58.0 versus 13.3, P <
      0.001). Hospital admission was common in both study groups. The incidence of
      hospitalisation was higher in the ulcer history group (477.3 versus 381.3, P <
      0.001); however, there were more foot-related hospital admissions in the dialysis
      group (32.9% versus 14.0%, P < 0.001) during the 30-month evaluation period. The
      incidence of ulcers, amputations and all-cause hospitalisations is high in
      persons with diabetes and a history of foot ulceration or on dialysis treatment;
      however, those on dialysis treatment have disproportionately higher rates of foot
      related hospitalisations. Intervention strategies to reduce the burden of
      diabetic foot disease must target dialysis patients as a high-risk group. 

PMID- 24103294
TI  - Activation of peripheral nerve fibers by electrical stimulation in the sole of
      the foot.
AB  - BACKGROUND: Human nociceptive withdrawal reflexes (NWR) can be evoked by
      electrical stimulation applied to the sole of the foot. However, elicitation of
      NWRs is highly site dependent, and NWRs are especially difficult to elicit at the
      heel. The aim of the present study was to investigate potential peripheral
      mechanisms for any site dependent differences in reflex thresholds. RESULTS: The
      first part of the study investigated the neural innervation in different sites of
      the sole of the foot using two different staining techniques. 1) Staining for the
      Nav1.7 antigen (small nociceptive fibers) and 2) the Sihler whole nerve technique
      (myelinated part of the nerve). No differences in innervation densities were
      found across the sole of the foot using the two staining techniques: Nav1.7
      immunochemistry (small nociceptive fibers (1-way ANOVA, NS)) and the Sihler's
      method (myelinated nerve fibers (1-way ANOVA, NS)). However, the results indicate
      that there are no nociceptive intraepidermal nerve fibers (IENFs) innervating the
      heel.Secondly, mathematical modeling was used to investigate to what degree
      differences in skin thicknesses affect the activation thresholds of Adelta and
      Abeta fibers in the sole of the foot. The modeling comprised finite element
      analysis of the volume conduction combined with a passive model of the activation
      of branching cutaneous nerve fibers. The model included three different sites in
      the sole of the foot (forefoot, arch and heel) and three different electrode
      sizes (diameters: 9.1, 12.9, and 18.3 mm). For each of the 9 combinations of site
      and electrode size, a total of 3000 Abeta fibers and 300 Adelta fibers was
      modeled. The computer simulation of the effects of skin thicknesses and
      innervation densities on thresholds of modeled Adelta and Abeta fibers did not
      reveal differences in pain and perception thresholds across the foot sole as have
      been observed experimentally. Instead a lack of IENFs at the heel decreased the
      electrical activation thresholds compared to models including IENFs. CONCLUSIONS:
      The nerve staining and modeling results do not explain differences in NWR
      thresholds across the sole of the foot which may suggest that central mechanisms
      contribute to variation in NWR excitability across the sole of the foot.

PMID- 24103295
TI  - Adrenocortical carcinoma initially presenting with hypokalemia and hypertension
      mimicking hyperaldosteronism: a case report.
AB  - BACKGROUND: Adrenocortical carcinoma is a rare malignancy and rare cause of
      Cushing's syndrome. CASE PRESENTATION: A 65-year-old seemingly well male patient
      was referred to our clinic under the suspicion of hyperaldosteronism due to
      hypertension combined with hypokalemia. However, his serum aldosterone and plasma
      renin activity were within normal limits. Instead, Cushing's syndrome was
      diagnosed by elevated urine free cortisol and a non-suppressible dexamethasone
      test. Abdominal computed tomography showed a 7.8 * 4.8 cm mass lesion at the
      right adrenal gland with liver invasion. Etomidate infusion was performed to
      reduce his cortisol level before the patient received a right adrenalectomy and
      liver wedge resection. The pathology report showed adrenocortical carcinoma with
      liver and lymph node metastasis. According to the European Network for the Study
      of Adrenal Tumors (ENSAT) staging system, the tumor was classified as T4N1M1,
      stage IV. Recurrent hypercortisolism was found shortly after surgery. The patient
      died of Fournier's gangrene with septic shock on the 59th day after diagnosis.
      CONCLUSIONS: We report a case of rapidly progressive stage IV adrenocortical
      carcinoma with initial presentations of hypokaelmia and hypertension, mimicking
      hyperaldosteronism.

PMID- 24103296
TI  - Rumination, anxiety, depressive symptoms and subsequent depression in adolescents
      at risk for psychopathology: a longitudinal cohort study.
AB  - BACKGROUND: A ruminative style of responding to low mood is associated with
      subsequent high depressive symptoms and depressive disorder in children,
      adolescents and adults. Scores on self-report rumination scales correlate
      strongly with scores on anxiety and depression symptom scales. This may confound
      any associations between rumination and subsequent depression. METHODS: Our
      sample comprised 658 healthy adolescents at elevated risk for psychopathology.
      This study applied ordinal item (non-linear) factor analysis to pooled items from
      three self-report questionnaires to explore whether there were separate, but
      correlated, constructs of rumination, depression and anxiety. It then tested
      whether rumination independently predicted depressive disorder and depressive
      symptoms over the subsequent 12 months, after adjusting for confounding
      variables. RESULTS: We identified a single rumination factor, which was
      correlated with factors representing cognitive symptoms of depression, somatic
      symptoms of depression and anxiety symptoms; and one factor representing adaptive
      responses to low mood. Elevated rumination scores predicted onset of depressive
      disorders over the subsequent year (p = 0.035), and levels of depressive symptoms
      12 months later (p < 0.0005), after adjustment for prior levels of depressive and
      anxiety symptoms. CONCLUSION: High rumination predicts onset of depressive
      disorder in healthy adolescents. Therapy that reduces rumination and increases
      distraction/problem-solving may reduce onset and relapse rates of depression.

PMID- 24103297
TI  - Genomics of Compositae crops: reference transcriptome assemblies and evidence of
      hybridization with wild relatives.
AB  - Although the Compositae harbours only two major food crops, sunflower and
      lettuce, many other species in this family are utilized by humans and have
      experienced various levels of domestication. Here, we have used next-generation
      sequencing technology to develop 15 reference transcriptome assemblies for
      Compositae crops or their wild relatives. These data allow us to gain insight
      into the evolutionary and genomic consequences of plant domestication.
      Specifically, we performed Illumina sequencing of Cichorium endivia, Cichorium
      intybus, Echinacea angustifolia, Iva annua, Helianthus tuberosus, Dahlia hybrida,
      Leontodon taraxacoides and Glebionis segetum, as well 454 sequencing of Guizotia
      scabra, Stevia rebaudiana, Parthenium argentatum and Smallanthus sonchifolius.
      Illumina reads were assembled using Trinity, and 454 reads were assembled using
      MIRA and CAP3. We evaluated the coverage of the transcriptomes using BLASTX
      analysis of a set of ultra-conserved orthologs (UCOs) and recovered most of these
      genes (88-98%). We found a correlation between contig length and read length for
      the 454 assemblies, and greater contig lengths for the 454 compared with the
      Illumina assemblies. This suggests that longer reads can aid in the assembly of
      more complete transcripts. Finally, we compared the divergence of orthologs at
      synonymous sites (Ks) between Compositae crops and their wild relatives and found
      greater divergence when the progenitors were self-incompatible. We also found
      greater divergence between pairs of taxa that had some evidence of postzygotic
      isolation. For several more distantly related congeners, such as chicory and
      endive, we identified a signature of introgression in the distribution of Ks
      values. 

PMID- 24103298
TI  - MicroRNAs with analogous target complementarities perform with highly variable
      efficacies in Arabidopsis.
AB  - In plants, the silencing efficacy of microRNAs (miRNAs) is thought to be
      predominantly determined by the degree of complementarity to their target genes.
      Here, silencing efficacy was determined for Arabidopsis miR159 and four
      artificial miRNAs (amiRNAs) that all target MYB33/MYB65 with analogous
      complementarities. As determined through complementation of a loss-of-function
      mir159 mutant, the amiRNAs displayed highly variable efficacies, none of which
      was as strong as endogenous miR159. This was despite amiRNA expression levels
      being many fold-higher than miR159 in wild-type. The results highlight the
      variable nature of miRNA silencing efficacy in plants, where it appears that
      factors additional to complementarity strongly impact silencing. 

PMID- 24103299
TI  - Synthesis and structure-activity relationships of phenyl-substituted coumarins
      with anti-tubercular activity that target FadD32.
AB  - In an effort to develop new and potent agents for therapy against tuberculosis, a
      high-throughput screen was performed against Mycobacterium tuberculosis strain
      H37Rv. Two 6-aryl-5,7-dimethyl-4-phenylcoumarin compounds 1a and 1b were found
      with modest activity. A series of coumarin derivatives were synthesized to
      improve potency and to investigate the structure-activity relationship of the
      series. Among them, compounds 1o and 2d showed improved activity with IC90 of 2
      MUM and 0.5 MUM, respectively. Further optimization provided compound 3b with
      better physiochemical properties with IC90 0.4 MUM which had activity in a mouse
      model of infection. The role of the conformation of the 4- and 6-aryl
      substituents is also described.

PMID- 24103300
TI  - Synthesis and immunological activity of an oligosaccharide-conjugate as a vaccine
      candidate against Group A Streptococcus.
AB  - The synthesis and immunogenicity of a tetanus toxoid (TT)-conjugate of the
      hexasaccharide portion of the cell-wall polysaccharide (CWPS) of the Group A
      Streptococcus (GAS) is described. The synthesis relies on the reaction of an
      allyl glycoside of the hexasaccharide with cysteamine, followed by the reaction
      of the resultant amine with diethyl squarate to give the monoethyl squarate
      adduct. Subsequent reaction with the lysine epsilon-amino groups on TT gives the
      glycoconjugate containing 30 hexasaccharide haptens per TT molecule. The
      immunogenicity in mice is similar to that obtained with a native CWPS-TT
      conjugate, validating the glycoconjugate as a vaccine candidate against GAS
      infections. 

PMID- 24103301
TI  - Epigenetics targeted protein-vorinostat nanomedicine inducing apoptosis in
      heterogeneous population of primary acute myeloid leukemia cells including
      refractory and relapsed cases.
AB  - Aberrant epigenetics play a key role in the onset and progression of acute
      myeloid leukemia (AML). Herein we report in silico modelling based development of
      a novel, protein-vorinostat nanomedicine exhibiting selective and superior anti
      leukemic activity against heterogeneous population of AML patient samples (n=9),
      including refractory and relapsed cases, and three representative cell lines
      expressing CD34(+)/CD38(-) stem cell phenotype (KG-1a), promyelocytic phenotype
      (HL-60) and FLT3-ITD mutation (MV4-11). Nano-vorinostat having ~100nm size
      exhibited enhanced cellular uptake rendering significantly lower IC50 in AML cell
      lines and patient samples, and induced enhanced HDAC inhibition, oxidative
      injury, cell cycle arrest and apoptosis compared to free vorinostat. Most
      importantly, nanomedicine showed exceptional single-agent activity against the
      clonogenic proliferative capability of bone marrow derived leukemic progenitors,
      while remaining non-toxic to healthy bone marrow cells. Collectively, this
      epigenetics targeted nanomedicine appears to be a promising therapeutic strategy
      against various French-American-British (FAB) classes of AML. FROM THE CLINICAL
      EDITOR: Through the use of a protein-vorinostat agent, exceptional single-agent
      activity was demonstrated against the clonogenic proliferative capability of bone
      marrow derived leukemic progenitors, while remaining non-toxic to healthy bone
      marrow cells. The studied epigenetics targeted nanomedicine approach is a
      promising therapeutic strategy against various French-American-British classes of
      acute myeloid leukemia.

PMID- 24103302
TI  - Nanomechanical properties and molecular structures of in vitro mineralized
      tissues on anodically-oxidized titanium surfaces.
AB  - The biomechanical stability of mineralized tissues at the interface between
      implant surface and bone tissue is of critical importance. Anodically oxidized
      titanium prepared in a chloride solution results in enhanced mineralization of
      adherent osteoblasts and has antimicrobial activity against oral microorganisms.
      We evaluated the nanomechanical properties and molecular structures of the in
      vitro mineralized tissues developing around anodically oxidized titanium surfaces
      with and without preparation in chloride solution. Anodically oxidized titanium
      surfaces showed superior osteogenic gene expressions than those of thermally
      oxidized and bare titanium surfaces. Preparation of anodically oxidized titanium
      in chloride enhanced the production of mineralized tissue around it. However, the
      mineralized tissue around anodically oxidized titanium prepared without chloride
      had increased mineral:matrix and cross-linking ratios, resulting in higher
      hardness and lower elasticity. FROM THE CLINICAL EDITOR: In this study anodically
      oxidized titanium was used to enhance the biomechanical stability of mineralized
      tissues at the implant surface -- bone tissue interface. The mineralized tissue
      around anodically oxidized titanium prepared without chloride had increased
      mineral:matrix and cross-linking ratios, resulting in higher hardness and lower
      elasticity.

PMID- 24103303
TI  - Use of surface-enhanced Raman scattering for detection of cancer-related serum
      constituents in gastrointestinal cancer patients.
AB  - Laser-mediated surface-enhanced Raman scattering (SERS) has industrial and
      biological applications. We have developed a rapid and simple method for
      generating silver nanoscale hexagonal columns (NHCs) on the surface of a phosphor
      bronze chip for measurement of SERS spectra. This was used to detect SERS spectra
      from blood samples obtained from patients with gastric cancer, colorectal cancer,
      or benign diseases (n=12 each) using a low intensity helium-neon red laser beam
      with a 632.8-nm wavelength; the intensity of the SERS spectra was compared among
      the patient groups. The peak heights of SERS spectra from patients with benign
      diseases were significantly lower than those from patients with gastric or
      colorectal cancer, whereas those from patients with gastric cancer and colorectal
      cancer did not differ significantly. Thus, SERS using NHC chips holds promise for
      the easier and faster detection of cancer-related serum-constituents as
      biomarkers. FROM THE CLINICAL EDITOR: In this study, laser-mediated surface
      enhanced Raman scattering (SERS) was utilized as a sensitive detection method of
      cancer-related serum-constituents in gastric and colorectal cancer, via the use
      of silver nanoscale hexagonal columns on the surface of a phosphor bronze chip
      for measurement of SERS spectra, paving the way to the development of a rapid and
      high throughput tool for cancer screening and therapy monitoring.

PMID- 24103305
TI  - In vivo MRI detection of carotid atherosclerotic lesions and kidney inflammation
      in ApoE-deficient mice by using LOX-1 targeted iron nanoparticles.
AB  - Lectin-like Oxidized Low-Density Lipoprotein Receptor 1 (LOX-1) plays a key role
      in atherosclerotic plaque initiation, formation and rupture, as well as in
      hyperlipidemia-induced glomerular disease. Here we report a sensitive, specific
      and biocompatible LOX-1-targeted-USPIO for the noninvasive MR imaging of LOX-1
      within carotid atherosclerotic lesions and glomerular disease in apoE-deficient
      mice. In vitro analysis showed the highest uptake of targeted USPIOs in only
      activated RAW264.7 macrophages, and in vivo MRI studies showed signal loss in
      carotid atherosclerotic lesions after administration of targeted USPIOs at 8h and
      24h. These areas of signal loss were correlated with the presence of
      nanoparticles in the atherosclerotic lesions, and immunohistochemistry and Perl's
      staining confirmed the co-localization of the LOX-1/macrophages/MMP-9 and
      targeted nanoparticles. Finally, additional studies suggest that this targeted
      probe may have potential to noninvasively image early glomerular disease. This
      finding may provide important methods for characterizing vulnerable
      atherosclerotic plaques and hyperlipidemia-induced glomerular diseases. FROM THE
      CLINICAL EDITOR: A functionalized USPIO-based negative contrast material was used
      in this study, demonstrating feasibility of sensitive MRI-based detection of
      atherosclerotic plaque formation in the carotid arteries and in the renal cortex,
      paving the way to potential future clinical applications.

PMID- 24103306
TI  - Non-mammalian vertebrate embryos as models in nanomedicine.
AB  - Various in vivo biological models have been proposed for studying the
      interactions of nano-materials in biological systems. Unfortunately, the widely
      used small mammalian animal models (rodents) are costly and labor intensive and
      generate ethical issues and antagonism from the anti-vivisectionist movement.
      Recently, there has been increasing interest in the scientific community in the
      interactions between nano-materials and non-mammalian developmental organisms,
      which are now being recognized as valid models for the study of human disease.
      This review examines and discusses the biomedical applications and the
      interaction of nano-materials with embryonic systems, focusing on non-mammalian
      vertebrate models, such as chicken, zebrafish and Xenopus. FROM THE CLINICAL
      EDITOR: Animal models are critical components of preclinical biomedical research.
      This review discusses the feasibility and potential applications of non-mammalian
      vertebral animals, such as zebrafish, xenopus, and chicken as animal models in
      nanomedicine research.

PMID- 24103304
TI  - Gold nanoparticle mediated cancer immunotherapy.
AB  - Significant progress has been made in the field of cancer immunotherapy, where
      the goal is to activate or modulate the body's immune response against cancer.
      However, current immunotherapy approaches exhibit limitations of safety and
      efficacy due to systemic delivery. In this context, the use of nanotechnology for
      the delivery of cancer vaccines and immune adjuvants presents a number of
      advantages such as targeted delivery to immune cells, enhanced therapeutic
      effect, and reduced adverse outcomes. Recently, gold nanoparticles (AuNP) have
      been explored as immunotherapy carriers, creating new AuNP applications that
      merit a critical overview. This review highlights recent advances in the
      development of AuNP mediated immunotherapies that harness AuNP biodistribution,
      optical properties and their ability to deliver macromolecules such as peptides
      and oligonucleotides. It has been demonstrated that the use of AuNP carriers can
      improve the delivery and safety of immunotherapy agents, and that AuNP
      immunotherapies are well suited for synergistic combination therapy with existing
      cancer therapies like photothermal ablation. FROM THE CLINICAL EDITOR: Cancer
      immunotherapy approaches are rapidly evolving and are some of the most promising
      avenues to approach malignancies. This review summarizes the role of gold
      nanoparticles in immunotherapy agent delivery, and in the development of
      synergistic therapies such as photothermal ablation.

PMID- 24103307
TI  - Nanohybrid structure analysis and biomolecule release behavior of polysaccharide
      CDHA drug carriers.
AB  - Nanoscaled polymer composites were prepared from polysaccharide chitosan (CS) and
      Ca-deficient hydroxyapatite (CDHA). CS-CDHA nanocomposites were synthesized by in
      situ precipitation at pH 9, and the CS-CDHA carriers were then fabricated by
      ionic cross-linking methods using tripolyphosphate and chemical cross-linking
      methods by glutaraldehyde and genipin. Certain biomolecules such as vitamin B12,
      cytochrome c, and bovine serum albumin were loaded into the CS-CDHA carriers, and
      their release behaviors were investigated. Furthermore, these CS-CDHA carriers
      were examined by transmission electron microscopy, electron spectroscopy for
      chemical analysis, and X-ray diffraction. The release behavior of the
      biomolecules was controlled by the CS/CDHA ratios and cross-linked agents. By
      increasing the concentration of CS and the concentration of the cross-linking
      agents, cross-linking within carriers increases, and the release rate of the
      biomolecules is decreased. Moreover, the release rate of the biomolecules from
      the CS-CDHA carriers at pH 4 was higher than that at pH 10, displaying a pH
      sensitive behavior. Therefore, these CS-CDHA hydrogel beads may be useful for
      intelligent drug release and accelerate bone reconstruction. 

PMID- 24103308
TI  - Analysis of cases of 3-methylcrotonyl CoA carboxylase deficiency (3-MCCD) in the
      California newborn screening program reported in the state database.
AB  - BACKGROUND AND METHODS: There are considerable uncertainty and debate regarding
      all aspects of newborn screen-positive cases of 3-methylcrotonyl-CoA carboxylase
      deficiency (3-MCCD), including diagnostic criteria, clinical spectrum, morbidity,
      prognosis, and appropriate management. To address some of these questions, we
      queried data from the California Newborn Screening Program's Screening
      Information System (SIS) and available scanned laboratory reports on cases of 3
      MCCD reported by 15 state contracted metabolic specialty care centers born
      between July 2005 and December 2010. We evaluated the completeness and utility of
      the database as a tool for clinical disease characterization. RESULTS: During the
      study period, 2,959,108 infants were screened and 71 infants were diagnosed with
      3-MCCD for an overall incidence of 1:41,676. The availability of diagnostic
      biochemical laboratory data varied significantly from subject to subject. Using a
      new case classification based on biochemical severity, we found that 8 of the
      cases met our criteria for biochemically severe (category 1), 19 cases met our
      criteria for biochemically mild (category 2) that we suspect to possibly be
      hypomorphic variants or heterozygote carriers, and 44 cases could not be
      classified (category 3) as mild or severe based on the data available in SIS.
      Documentation of the treatment regimens also varied significantly with 49%
      receiving dietary modification and 44% receiving carnitine. 15% of cases were
      documented to have experienced at least one of the following symptoms: lethargy,
      vomiting, irritability, ketosis, poor feeding, or poor tone. The majority of the
      subjects were completely developmentally age appropriate at their last
      assessment. CONCLUSIONS: The results suggest that a significant portion of the 3
      MCCD "confirmed" cases have a mild biochemical phenotype. Moreover the majority
      of cases had insufficient data entered to allow for adequate clinical
      characterization of the cases. These findings raise the concern that a
      significant number of individuals receiving treatment for 3-MCCD may not have a
      clinically significant condition. Additionally, the utility of this data system
      could be improved if centers provided complete confirmatory test results and more
      specific documentation of clinical outcomes and health/developmental status.
      Further studies, including a clinical chart review, are necessary to validate the
      data and further characterize this cohort.

PMID- 24103309
TI  - Synthesis and antimycobacterial activity of novel thiadiazolylhydrazones of 1
      substituted indole-3-carboxaldehydes.
AB  - A series of novel thiocarbohydrazones of substituted indoles and their
      corresponding thiadiazole derivatives were prepared, and their structures were
      confirmed by different analytical and spectroscopic methods. The derivatives were
      prepared by a sequential synthetic strategy including substitution at N-1
      position of indole ring by various aliphatic and benzylic substituents, followed
      by condensation with thiocarbohydrazide, and finally cyclization by triethyl
      orthoformate. The derivatives were tested for their antimycobacterial activity
      against Mycobacterium bovis BCG, and the results revealed that among the
      synthesized compounds, thiadiazole derivatives 4e, 4f, 4n, 4p, 4q, and 4t
      exhibited the highest activity with IC50 value of 3.91 MUg/mL. The results
      indicate that the thiadiazole moiety plays a vital role in exerting
      antimycobacterial activity.

PMID- 24103311
TI  - Reversal of deficits in dendritic spines, BDNF and Arc expression in the amygdala
      during alcohol dependence by HDAC inhibitor treatment.
AB  - Development of anxiety-like behaviours during ethanol withdrawal has been
      correlated with increased histone deacetylase (HDAC) activity and decreased brain
      derived neurotrophic factor (BDNF) and activity-regulated cytoskeleton-associated
      protein (Arc) gene expression in the amygdala. Furthermore, HDAC-mediated histone
      modifications play a role in synaptic plasticity. In this study we used the HDAC
      inhibitor trichostatin A (TSA) to determine whether HDAC inhibition could prevent
      ethanol withdrawal-induced deficits in dendritic spine density (DSD), BDNF or Arc
      expression in the amygdala of rats. It was found that decreased BDNF and Arc
      expression in the central (CeA) and medial nucleus of amygdala (MeA), observed
      during withdrawal after chronic ethanol exposure, were normalized following acute
      TSA treatment. TSA treatment was also able to attenuate anxiety-like behaviours
      during ethanol withdrawal and correct the observed decrease in DSD in the CeA and
      MeA of ethanol-withdrawn rats. Taken together, these findings demonstrate that
      correcting the deficits in histone acetylation through TSA treatment also amends
      downstream synaptic plasticity-related deficits such as BDNF and Arc expression,
      and DSD in the CeA and MeA as well as attenuates anxiety-like behaviours in rats
      during withdrawal after chronic ethanol exposure. 

PMID- 24103310
TI  - Executive function in children with attention deficit/hyperactivity disorder: the
      NIH EXAMINER battery.
AB  - Theories of attention deficit/hyperactivity disorder (ADHD) increasingly
      highlight the role of neuropsychological impairment in ADHD; however, a
      consistent and identifiable pattern of performance on tests is not well
      established. The National Institutes of Health (NIH) Executive Abilities:
      Measures and Instruments for Neurobehavioral Evaluation and Research (EXAMINER)
      battery provides measures of common variance across multiple executive function
      tests within specific domains and was used to characterize which executive
      functions are most affected in children with ADHD. Thirty-two children (24 male),
      ages 8-15 years (M = 12.02; SD = 2.29), diagnosed with ADHD and no comorbid
      disorder completed the NIH EXAMINER battery. Sixty age and gender matched healthy
      controls were chosen from a database of participants enrolled in the NIH EXAMINER
      multi-site study. Children with ADHD performed worse on the working memory score
      compared with the controls. No differences were found on the cognitive control or
      fluency scores. For children with ADHD, poorer working memory performance
      predicted parent report of child learning problems. Cognitive control and fluency
      scores did not predict learning problems. In summary, working memory emerges as a
      primary impairment in children with ADHD who have no comorbid disorders.
      Furthermore, working memory weaknesses may underlie the academic problems often
      seen in children with ADHD.

PMID- 24103314
TI  - Aerobic Activity Preferences among Older Canadians: A Time Use Perspective.
AB  - Numerous health benefits are associated with a physically active population. This
      study sought to discover the aerobic activity preferences among older Canadians.
      Four cycles of nationally representative time use data were fused with energy
      expenditure information to determine both participation rates and time spent in
      the 10 most frequently reported aerobic activities. Aerobic activity preferences
      are dominated by domestic chores (15% to 30% participation for about two hours
      per day), recreational walking (15% to 30% participation for about one hour per
      day), and active transportation (generally less than 5% participation for less
      than 30 minutes per day). Although there have been several changes in older
      Canadians' revealed preferences for aerobic activities over the past three
      decades, the prevalence of domestic chores points towards the importance of
      policies that support older Canadians remaining in their homes, whereas the
      popularity of walking suggests that "walkability" needs to be considered in
      neighbourhood design.

PMID- 24103313
TI  - 17beta-Estradiol alters oxidative stress response protein expression and
      oxidative damage in the uterus.
AB  - The steroid hormone 17beta-estradiol (E2) has profound effects on the uterus.
      However, with the E2-induced increase in uterine cell proliferation and
      metabolism comes increased production of reactive oxygen species (ROS). We
      examined the expression of an interactive network of oxidative stress response
      proteins including thioredoxin (Trx), Cu/Zn superoxide dismutase (SOD1), apurinic
      endonuclease (Ape1), and protein disulfide isomerase (PDI). We demonstrated that
      treatment of ovariectomized C57BL/6J female mice with E2 increased the mRNA and
      protein levels of Trx, but decreased SOD1 and Ape1 mRNA and protein expression.
      In contrast, E2 treatment increased PDI protein levels but had no effect on PDI
      transcript levels. Interestingly, E2 treatment also increased two markers of
      cellular damage, lipid peroxidation and protein carbonylation. Our studies
      suggest that the decreased expression of SOD1 and Ape1 caused by E2 treatment may
      in the long term result in disruption of ROS regulation and play a role in
      endometrial carcinogenesis. 

PMID- 24103312
TI  - Mechanism of androgen receptor corepression by CKbetaBP2/CRIF1, a multifunctional
      transcription factor coregulator expressed in prostate cancer.
AB  - The transcription factor coregulator Casein kinase IIbeta-binding protein 2 or
      CR6-interacting factor 1 (CKbetaBP2/CRIF1) binds the androgen receptor (AR) in
      prostate cancer cells and in response to dihydrotestosterone localizes with AR on
      the prostate-specific antigen gene enhancer, but does not bind DNA suggesting
      CKbetaBP2/CRIF1 localization in chromatin is determined by AR. In this study we
      show also that CKbetaBP2/CRIF1 inhibits wild-type AR and AR N-terminal
      transcriptional activity, binds to the AR C-terminal region, inhibits interaction
      of the AR N- and C-terminal domains (N/C interaction) and competes with p160
      coactivator binding to the AR C-terminal domain, suggesting CKbetaBP2/CRIF1
      interferes with AR activation functions 1 and 2. CKbetaBP2/CRIF1 is expressed
      mainly in stromal cells of benign prostatic hyperplasia and in stroma and
      epithelium of prostate cancer. CKbetaBP2/CRIF1 protein is increased in epithelium
      of androgen-dependent prostate cancer compared to benign prostatic hyperplasia
      and decreased slightly in castration recurrent epithelium compared to androgen
      dependent prostate cancer. The multifunctional CKbetaBP2/CRIF1 is a STAT3
      interacting protein and reported to be a coactivator of STAT3. CKbetaBP2/CRIF1 is
      expressed with STAT3 in prostate cancer where STAT3 may help to offset the AR
      repressor effect of CKbetaBP2/CRIF1 and allow AR regulation of prostate cancer
      growth. 

PMID- 24103316
TI  - [Ruptured renal artery aneurysms in microscopic polyangiitis].
AB  - INTRODUCTION: Renal artery aneurysms are unusual manifestations of microscopic
      polyangiitis. OBSERVATION: We report the case of a 55 years old male patient,
      with a microscopic polyangiitis, which was revealed by a demyelinating
      polyradiculoneuropathy, the diagnosis was made with association of alveolar
      hemorrhage, peripheral neuropathy and glomerulonephritis with positive
      antineutrophil cytoplasmic antibodies (antimyeloperoxidase antibodies). The
      evolution was marked by a state of shock by rupture of aneurysms of intrarenal
      arteries. CONCLUSION: This case emphasizes the importance of looking for
      complications of unusual type of intrarenal aneurysms in patients with
      microscopic polyngiitis.

PMID- 24103315
TI  - Ethnic specificity of variants of the ESR1, HK3, BRSK1 genes and the 8q22.3
      locus: no association with premature ovarian failure (POF) in Serbian women.
AB  - OBJECTIVE: To identify whether variants found in a large Han Chinese cohort -
      8q22.3 SNPs rs3847153 and rs3108910; and one SNP each in HK3 (rs2278493), ESR1
      (rs2234693) and BRSK1 (rs12611091) - are associated with premature ovarian
      failure (POF) in a different ethnic group (Serbian). DESIGN: Case-control genetic
      association study in 197 Serbian POF cases and 552 matched controls. RESULTS:
      None of the SNPs found associated with POF in Chinese cohort were found to be
      associated in the Serbian sample. CONCLUSIONS: In contrast to Han Chinese, no
      association was found between POF in Serbian women and any of the four tested
      loci: 8q22.3, HK3, ESR1 and BRSK1. This indicates that ethnically distinct
      populations may show differences in gene-regulating pathways and genes causing
      POF.

PMID- 24103317
TI  - Synthesis of guanidinoacetate and creatine from amino acids by rat pancreas.
AB  - Creatine is an important molecule involved in cellular energy metabolism.
      Creatine is spontaneously converted to creatinine at a rate of 1.7% per d;
      creatinine is lost in the urine. Creatine can be obtained from the diet or
      synthesised from endogenous amino acids via the enzymes arginine:glycine
      amidinotransferase (AGAT) and guanidinoacetate N-methyltransferase (GAMT). The
      liver has high GAMT activity and the kidney has high AGAT activity. Although the
      pancreas has both AGAT and GAMT activities, its possible role in creatine
      synthesis has not been characterised. In the present study, we examined the
      enzymes involved in creatine synthesis in the pancreas as well as the synthesis
      of guanidinoacetate (GAA) and creatine by isolated pancreatic acini. We found
      significant AGAT activity and somewhat lower GAMT activity in the pancreas and
      that pancreatic acini had measurable activities of both AGAT and GAMT and the
      capacity to synthesise GAA and creatine from amino acids. Creatine
      supplementation led to a decrease in AGAT activity in the pancreas, though it did
      not affect its mRNA or protein abundance. This was in contrast with the reduction
      of AGAT activity and mRNA and protein abundance in the kidney, suggesting that
      the regulatory mechanisms that control the expression of this enzyme in the
      pancreas are different from those in the kidney. Dietary creatine increased the
      concentrations of GAA, creatine and phosphocreatine in the pancreas.
      Unexpectedly, creatine supplementation decreased the concentrations of S
      adenosylmethionine, while those of S-adenosylhomocysteine were not altered
      significantly.

PMID- 24103319
TI  - Rose geranium essential oil as a source of new and safe anti-inflammatory drugs.
AB  - BACKGROUND: Since the available anti-inflammatory drugs exert an extensive
      variety of side effects, the search for new anti-inflammatory agents has been a
      priority of pharmaceutical industries. AIMS: The aim of the present study was to
      assess the anti-inflammatory activities of the essential oil of rose geranium
      (RGEO). METHODS: The chemical composition of the RGEO was investigated by gas
      chromatography. The major components were citronellol (29.13%), geraniol
      (12.62%), and citronellyl formate (8.06%). In the carrageenan-induced paw edema,
      five different groups were established and RGEO was administered orally in three
      different doses. RESULTS: RGEO (100 mg/kg) was able to significantly reduce the
      paw edema with a comparable effect to that observed with diclofenac, the positive
      control. In addition, RGEO showed a potent anti-inflammatory activity by topical
      treatment in the method of croton oil-induced ear edema. When the dose was 5 or
      10 ul of RGEO per ear, the inflammation was reduced by 73 and 88%, respectively.
      This is the first report to demonstrate a significant anti-inflammatory activity
      of Algerian RGEO. In addition, histological analysis confirmed that RGEO
      inhibited the inflammatory responses in the skin. CONCLUSION: Our results
      indicate that RGEO may have significant potential for the development of novel
      anti-inflammatory drugs with improved safety profile.

PMID- 24103318
TI  - Wikis and collaborative writing applications in health care: a scoping review.
AB  - BACKGROUND: Collaborative writing applications (eg, wikis and Google Documents)
      hold the potential to improve the use of evidence in both public health and
      health care. The rapid rise in their use has created the need for a systematic
      synthesis of the evidence of their impact as knowledge translation (KT) tools in
      the health care sector and for an inventory of the factors that affect their use.
      OBJECTIVE: Through the Levac six-stage methodology, a scoping review was
      undertaken to explore the depth and breadth of evidence about the effective,
      safe, and ethical use of wikis and collaborative writing applications (CWAs) in
      health care. METHODS: Multiple strategies were used to locate studies. Seven
      scientific databases and 6 grey literature sources were queried for articles on
      wikis and CWAs published between 2001 and September 16, 2011. In total, 4436
      citations and 1921 grey literature items were screened. Two reviewers
      independently reviewed citations, selected eligible studies, and extracted data
      using a standardized form. We included any paper presenting qualitative or
      quantitative empirical evidence concerning health care and CWAs. We defined a CWA
      as any technology that enables the joint and simultaneous editing of a webpage or
      an online document by many end users. We performed qualitative content analysis
      to identify the factors that affect the use of CWAs using the Gagnon framework
      and their effects on health care using the Donabedian framework. RESULTS: Of the
      111 studies included, 4 were experimental, 5 quasi-experimental, 5 observational,
      52 case studies, 23 surveys about wiki use, and 22 descriptive studies about the
      quality of information in wikis. We classified them by theme: patterns of use of
      CWAs (n=26), quality of information in existing CWAs (n=25), and CWAs as KT tools
      (n=73). A high prevalence of CWA use (ie, more than 50%) is reported in 58%
      (7/12) of surveys conducted with health care professionals and students. However,
      we found only one longitudinal study showing that CWA use is increasing in health
      care. Moreover, contribution rates remain low and the quality of information
      contained in different CWAs needs improvement. We identified 48 barriers and 91
      facilitators in 4 major themes (factors related to the CWA, users' knowledge and
      attitude towards CWAs, human environment, and organizational environment). We
      also found 57 positive and 23 negative effects that we classified into processes
      and outcomes. CONCLUSIONS: Although we found some experimental and quasi
      experimental studies of the effectiveness and safety of CWAs as educational and
      KT interventions, the vast majority of included studies were observational case
      studies about CWAs being used by health professionals and patients. More primary
      research is needed to find ways to address the different barriers to their use
      and to make these applications more useful for different stakeholders.

PMID- 24103320
TI  - Differential associations of angiographic extent and severity of coronary artery
      disease with asymmetric dimethylarginine but not insulin resistance in non
      diabetic men with stable angina: a cross-sectional study.
AB  - BACKGROUND: Asymmetric dimethylarginine (ADMA), an endogenous nitric oxide
      synthesis inhibitor, and insulin resistance (IR) have been implicated in
      atherogenesis. Our aim was to estimate relations between ADMA, the magnitude of
      IR and angiographic indices of extent and severity of coronary atherosclerosis in
      non-diabetic men with stable coronary artery disease (CAD). METHODS: We studied
      151 non-diabetic men (mean age 57 +/- 11 years) with stable angina, obstructive
      CAD (at least 1 luminal diameter stenosis of >=70% in major coronary segments)
      and without heart failure, and 34 age-matched controls free of >=50% coronary
      narrowings. The following CAD indices were computed: the number of major
      epicardial vessels with >=70% stenosis, Sullivan extent score representing a
      proportion of the visible coronary tree with vessel wall irregularities, and
      Gensini score which reflects both CAD severity and extent, yet assigning a
      heavier weight to proximal segments and to the more severe narrowings by a non
      linear point system. An estimate of IR was derived by homeostasis model
      assessment (HOMA-IR) from fasting insulin and glucose. RESULTS: Among the CAD
      patients, the proportions of subjects with 1-vessel, 2- vessel and 3-vessel CAD
      were 26%, 25% and 49%, respectively. ADMA levels were higher in patients with
      obstructive CAD compared to the controls (0.51 +/- 0.10 vs. 0.46 +/- 0.09 MUmol/L
      [SD], P = 0.01), whereas HOMA-IR was similar (median, 3.2 [interquartile range:
      2.4-4.9] vs. 2.9 [2.3-4.7], P = 0.2). Within the CAD group, ADMA increased across
      ascending quartiles of Sullivan score (Spearman's rho = 0.23, P = 0.004), but not
      with Gensini score (rho = 0.12, P = 0.15) or the number of vessels involved (rho
      = 0.08, P = 0.3). ADMA correlated to log-transformed Sullivan score (Pearson's r
      = 0.21, P = 0.008), which was only slightly attenuated upon multivariate
      adjustment (beta = 0.19 +/- 0.08 [SEM], P = 0.015). HOMA-IR did not differ
      according to any measure of angiographic CAD (P >= 0.2). ADMA and log (HOMA-IR)
      were mutually unrelated (r = 0.07, P = 0.4). CONCLUSIONS: ADMA is associated with
      diffuse but not focal coronary atherosclerosis in non-diabetic men with stable
      CAD irrespectively of the degree of IR. The independent relationship between ADMA
      and coronary atherosclerotic burden may contribute to the well-recognized
      prognostic effect of ADMA in CAD.

PMID- 24103322
TI  - Examination of categorical approach to symptom assessment: cross-validation of
      foulds' Delusions-Symptoms-States Inventory with Korean non-patient and patient
      groups.
AB  - BACKGROUND: Foulds' Delusions-Symptoms-State Inventory (DSSI) has been purported
      to be a reliable, systematic categorical measure to assess the patients with
      schizophrenia according to the degree of illness. However, further cross
      validations using other clinical measures and diverse samples from other cultures
      have not been advanced recently. We aimed to examine the validity of the DSSI
      hierarchical class model using both Korean non-patient and patient (schizophrenia
      and depression) groups. METHOD: The hypothesis of inclusive, non-reflexive
      relationships among the DSSI classes was tested. The power of DSSI to detect
      presence of symptoms was assessed via cross-validation with other clinical
      measures, and the differences between the clinical features among the DSSI
      classes were examined using the Minnesota Multiphasic Personality Inventory
      (MMPI). RESULTS: The high rate of model conformity (91.1%) across the samples and
      cross-validation with other criterion measures provided further support for the
      validity of DSSI. CONCLUSIONS: DSSI is a reliable self-report measure that can be
      applied to both patient and non-patients to assess the presence and severity of
      psychiatric illness. Future studies that include more diverse clinical groups are
      necessary to lend further support for its utility in clinical practice.

PMID- 24103321
TI  - [Dementia: Where are the Lewy bodies?].
AB  - Dementia with Lewy bodies (DLB) is the second cause of degenerative dementia in
      autopsy studies. In clinical pratice however, the prevalence of DLB is much lower
      with important intercenter variations. Among the reasons for this low sensitivity
      of DLB diagnosis are (1) the imprecision and subjectivity of the diagnostic
      criteria; (2) the underestimation of non-motor symptoms (REM-sleep behavior
      disorder, dysautonomia, anosmia); mostly (3) the nearly constant association of
      Lewy bodies with Alzheimer's disease pathology, which dominates the clinical
      phenotype. With the avenue of targeted therapies against the protein agregates,
      new clinical scales able to apprehend the coexistence of Lewy pathology in
      Alzheimer's disease are expected. 

PMID- 24103323
TI  - Regional differences in trait-like characteristics of the waking EEG in early
      adolescence.
AB  - BACKGROUND: The human waking EEG spectrum shows high heritability and stability
      and, despite maturational cortical changes, high test-retest reliability in
      children and teens. These phenomena have also been shown to be region specific.
      We examined the stability of the morphology of the wake EEG spectrum in children
      aged 11 to 13 years recorded over weekly intervals and assessed whether the
      waking EEG spectrum in children may also be trait-like. Three minutes of eyes
      open and three minutes of eyes closed waking EEG was recorded in 22 healthy
      children once a week for three consecutive weeks. Eyes open and closed EEG power
      density spectra were calculated for two central (C3LM and C4LM) and two occipital
      (O1LM and O2LM) derivations. A hierarchical cluster analysis was performed to
      determine whether the morphology of the waking EEG spectrum between 1 and 20 Hz
      is trait-like. We also examined the stability of the alpha peak using an ANOVA.
      RESULTS: The morphology of the EEG spectrum recorded from central derivations was
      highly stable and unique to an individual (correctly classified in 85% of
      participants), while the EEG recorded from occipital derivations, while stable,
      was much less unique across individuals (correctly classified in 42% of
      participants). Furthermore, our analysis revealed an increase in alpha peak
      height concurrent with a decline in the frequency of the alpha peak across weeks
      for occipital derivations. No changes in either measure were observed in the
      central derivations. CONCLUSIONS: Our results indicate that across weekly
      recordings, power spectra at central derivations exhibit more "trait-like"
      characteristics than occipital derivations. These results may be relevant for
      future studies searching for links between phenotypes, such as psychiatric
      diagnoses, and the underlying genes (i.e., endophenotypes) by suggesting that
      such studies should make use of more anterior rather than posterior EEG
      derivations.

PMID- 24103324
TI  - Comparative studies on species identification of Noctuoidea moths in two nature
      reserve conservation zones (Beijing, China) using DNA barcodes and thin-film
      biosensor chips.
AB  - Rapid and accurate identification of species is required for the biological
      control of pest Noctuoidea moths. DNA barcodes and thin-film biosensor chips are
      two molecular approaches that have gained wide attention. Here, we compare these
      two methods for the identification of a limited number of Noctuoidea moth
      species. Based on the commonly used mitochondrial gene cytochrome c oxidase I
      (the standard DNA barcode for animal species), 14 probes were designed and
      synthesized for 14 species shared by two national nature reserves in Beijing and
      Hebei, China. Probes ranged in length from 18 to 27 bp and were designed as
      mismatch probes to guarantee that there were at least three base differences
      between the probe and nontarget sequences. The results on the chip could be
      detected by the naked eye without needing special equipment. No cross
      hybridizations were detected although we tested all probes on the 14 target and
      24 nontarget Noctuoidea species. The neighbour-joining tree of the 38 species
      based on COI sequences gave 38 highly supported independent groups. Both DNA
      barcoding and thin-film biosensor chips, based on the COI gene, are able to
      accurately identify and discriminate the 14 targeted moth species in this study.
      Because of its speed, high accuracy and low cost, the thin-film biosensor chip is
      a very practical means of species identification. Now, a more comprehensive chip
      will be developed for the identification of additional Noctuoidea moths for pest
      control and ecological protection. 

PMID- 24103325
TI  - Fixation of CO2 in Clostridium cellulovorans analyzed by 13C-isotopomer-based
      target metabolomics.
AB  - Clostridium cellulovorans has been one of promising microorganisms to use biomass
      efficiently; however the basic metabolic pathways have not been completely known.
      We carried out 13C-isotopomer-based target metabolome analysis, or carbohydrate
      conversion process analysis, for more profound understanding of metabolic
      pathways of the bacterium. Our findings that pyruvate + oxaloacetate, fumarate,
      and malate inside and outside cells exhibited 13C incorporation suggest that C.
      cellulovorans exactly fixed CO2 and partly operated the TCA cycle in a reductive
      manner. Accompanied with CO2 fixation, the microorganism was also found to
      produce and secrete lactate. Overall, our study demonstrates that a part of C.
      cellulovorans metabolic pathways related to glycolysis and the TCA cycle are
      involved in CO2 fixation. 

PMID- 24103326
TI  - Physical activity and sedentary behaviour in European children: the IDEFICS
      study.
AB  - OBJECTIVE: To estimate the prevalence of physical activity and sedentary
      behaviours in European children, and to evaluate the relationship between media
      availability in personal space and physical activity in relation to total screen
      time. DESIGN: Data from the baseline IDEFICS (Identification and prevention of
      dietary- and lifestyle-induced health effects in children and infants) cross
      sectional survey. Information on hours of television/digital video disk/video
      viewing and computer/games-console use (weekday and weekend days), media device
      availability in personal space, sports club membership, hours of active organized
      play and commuting (to and from school) were assessed via a self-reported
      parental questionnaire. Total screen time was defined as the sum of daily media
      use and subsequently dichotomized into meeting or not meeting the guidelines of
      the American Academy of Pediatrics. SETTING: Eight survey centres (Italy,
      Estonia, Cyprus, Belgium, Sweden, Germany, Hungary and Spain). SUBJECTS: Children
      (n 15 330; 51% males) aged 2-10 years. RESULTS: Percentage of children engaged in
      total screen time for >2 h/d was higher on weekend days (52% v. 20% on weekdays)
      and in the older group (71% in males; 57% in females), varying by country.
      Children with a television set in their bedroom were more likely not to meet the
      screen time recommendations (OR = 1.54; 95% CI 1.60, 1.74). CONCLUSIONS:
      Approximately a third of the children failed to meet current screen time
      recommendations. Availability of a television set in personal space increased the
      risk of excess total screen time. This information could be used to identify
      potential targets for public health promotion actions of young population groups.

PMID- 24103327
TI  - Soluble ST2 in ambulatory patients with heart failure: Association with
      functional capacity and long-term outcomes.
AB  - BACKGROUND: ST2 is involved in cardioprotective signaling in the myocardium and
      has been identified as a potentially promising biomarker in heart failure (HF).
      We evaluated ST2 levels and their association with functional capacity and long
      term clinical outcomes in a cohort of ambulatory patients with HF enrolled in the
      Heart Failure: A Controlled Trial Investigating Outcomes of Exercise Training (HF
      ACTION) study-a multicenter, randomized study of exercise training in HF. METHODS
      AND RESULTS: HF-ACTION randomized 2331 patients with left ventricular ejection
      fraction <0.35 and New York Heart Association class II to IV HF to either
      exercise training or usual care. ST2 was analyzed in a subset of 910 patients
      with evaluable plasma samples. Correlations and Cox models were used to assess
      the relationship among ST2, functional capacity, and long-term outcomes. The
      median baseline ST2 level was 23.7 ng/mL (interquartile range, 18.6-31.8). ST2
      was modestly associated with measures of functional capacity. In univariable
      analysis, ST2 was significantly associated with death or hospitalization (hazard
      ratio, 1.48; P<0.0001), cardiovascular death or HF hospitalization (hazard ratio,
      2.14; P<0.0001), and all-cause mortality (hazard ratio, 2.33; P<0.0001; all
      hazard ratios for log2 ng/mL). In multivariable models, ST2 remained
      independently associated with outcomes after adjustment for clinical variables
      and amino-terminal pro-B-type natriuretic peptide. However, ST2 did not add
      significantly to reclassification of risk as assessed by changes in the C
      statistic, net reclassification improvement, and integrated discrimination
      improvement. CONCLUSIONS: ST2 was modestly associated with functional capacity
      and was significantly associated with outcomes in a well-treated cohort of
      ambulatory patients with HF although it did not significantly affect
      reclassification of risk. CLINICAL TRIAL INFORMATION: URL:
      http://www.clinicaltrials.gov. Unique identifier: NCT00047437.

PMID- 24103328
TI  - Locking the active conformation of c-Src kinase through the phosphorylation of
      the activation loop.
AB  - Molecular dynamics umbrella sampling simulations are used to compare the relative
      stability of the active conformation of the catalytic domain of c-Src kinase
      while the tyrosine 416 in the activation loop (A-loop) is either unphosphorylated
      or phosphorylated. When the A-loop is unphosphorylated, there is considerable
      flexibility of the kinase. While the active conformation of the kinase is not
      forbidden and can be visited transiently, it is not the predominant state. This
      is consistent with the view that c-Src displays some catalytic activity even when
      the A-loop is unphosphorylated. In contrast, phosphorylation of the A-loop
      contributes to stabilize several structural features that are critical for
      catalysis, such as the hydrophobic regulatory spine, the HRD motif, and the
      electrostatic switch. In summary, the free-energy landscape calculations
      demonstrate that phosphorylation of tyrosine 416 in the A-loop essentially
      "locks" the kinase into its catalytically competent conformation. 

PMID- 24103329
TI  - Multiple mechanisms for E2F binding inhibition by phosphorylation of the
      retinoblastoma protein C-terminal domain.
AB  - The retinoblastoma protein C-terminal domain (RbC) is necessary for the tumor
      suppressor protein's activities in growth suppression and E2F transcription
      factor inhibition. Cyclin-dependent kinase phosphorylation of RbC contributes to
      Rb inactivation and weakens the Rb-E2F inhibitory complex. Here we demonstrate
      two mechanisms for how RbC phosphorylation inhibits E2F binding. We find that
      phosphorylation of S788 and S795 weakens the direct association between the N
      terminal portion of RbC (RbC(N)) and the marked-box domains of E2F and its
      heterodimerization partner DP. Phosphorylation of these sites and S807/S811 also
      induces an intramolecular association between RbC and the pocket domain, which
      overlaps with the site of E2F transactivation domain binding. A reduction in E2F
      binding affinity occurs with S788/S795 phosphorylation that is additive with the
      effects of phosphorylation at other sites, and we propose a structural mechanism
      that explains this additivity. We find that different Rb phosphorylation events
      have distinct effects on activating E2F family members, which suggests a novel
      mechanism for how Rb may differentially regulate E2F activities. 

PMID- 24103330
TI  - Polymorphism in the TOMM40 gene modifies the risk of developing sporadic
      inclusion body myositis and the age of onset of symptoms.
AB  - A polyT repeat in an intronic polymorphism (rs10524523) in the TOMM40 gene, which
      encodes an outer mitochondrial membrane translocase involved in the transport of
      amyloid-beta and other proteins into mitochondria, has been implicated in
      Alzheimer's disease and APOE-TOMM40 genotypes have been shown to modify disease
      risk and age at onset of symptoms. Because of the similarities between
      Alzheimer's disease and sporadic inclusion body myositis (s-IBM), and the
      importance of amyloid-beta and mitochondrial changes in s-IBM, we investigated
      whether variation in poly-T repeat lengths in rs10524523 also influence
      susceptibility and age at onset in a cohort of 90 Caucasian s-IBM patients (55
      males; age 69.1 +/- 9.6). In carriers of APOE epsilon3/epsilon3 or
      epsilon3/epsilon4, genotypes with a very long (VL) poly-T repeat were under
      represented in s-IBM compared to controls and were associated with a later age at
      symptom onset, suggesting that these genotypes may be protective. Our study is
      the first to suggest that polymorphisms in genes controlling mitochondrial
      function can influence susceptibility to s-IBM and have disease modifying
      effects. However, further studies in other s-IBM populations are needed to
      confirm these findings, as well as expression studies of different TOMM40 alleles
      in muscle tissue.

PMID- 24103331
TI  - Incidence of symptomatic A(H1N1)pdm09 influenza during the pandemic and post
      pandemic periods in a rural Indian community.
AB  - BACKGROUND: Data on influenza illness rates with population denominators are
      needed to quantify overall morbidity and to prioritize public health intervention
      strategies. METHODS: The rates of influenza A(H1N1)pdm09 infection during
      pandemic phases were determined in a longitudinal community cohort study as part
      of an influenza vaccine study in a rural community of North India. RESULTS:
      During the 711,731 person-weeks of surveillance, a total of 1410/7571 (19%)
      febrile acute respiratory illness cases were positive for influenza. Of these,
      749 (53%) were influenza A(H1N1)pdm09, 643 (46%) influenza B, and 18 (1%)
      influenza A (H3N2). The overall incidence rate of influenza-associated febrile
      acute respiratory illness was 128/1000 person-years. The incidence rates of
      influenza A(H1N1)pdm09 were high during both the pandemic phase (179/1000 person
      years; November 2009 to January 2010) and post-pandemic phase (156/1000 person
      years; August to October 2010), with children<18 years of age being at the
      greatest risk of influenza infection in the community. CONCLUSIONS: These
      findings provide important information for planning clinical and public health
      intervention strategies to mitigate the impact of influenza epidemics.

PMID- 24103332
TI  - Seroprevalence of Toscana virus infection in Tunisia.
AB  - OBJECTIVES: The main objective of this study was to assess the prevalence of IgG
      antibodies against Toscana virus (TOSV) by an ELISA test and to determine the
      extent of its circulation in Tunisia. METHODS: An indirect ELISA test was
      performed to detect anti-TOSV IgG. The results were compared to those of an
      indirect fluorescent antibody (IFA) test. RESULTS: The survey tested 494 healthy
      people from various regions of Tunisia by ELISA for anti-TOSV IgG; 47 people
      (9.5%) were found to be positive. Seroprevalence varied by bioclimatic region and
      gender. Two hundred and twelve samples, randomly chosen from the same selected
      population and tested with ELISA, were retested using an IFA for IgG antibodies.
      An 85% concordance between the IFA and ELISA was obtained (kappa=0.650).
      CONCLUSIONS: These serological data confirm the circulation of TOSV in different
      bioclimatic zones in Tunisia where the vector sand flies are found. The detection
      of IgG against TOSV suggests that the diagnosis of TOSV infection is often
      neglected, as this virus often causes asymptomatic infections, with only a few
      patients developing severe illnesses involving neurological manifestations.

PMID- 24103333
TI  - Molecular detection and genetic identification of Borrelia garinii and Borrelia
      afzelii from patients presenting with a rare skin manifestation of prurigo
      pigmentosa in Taiwan.
AB  - OBJECTIVES: To determine the genetic identity of Borrelia spirochetes isolated
      from patients with an unusual skin lesion of prurigo pigmentosa (PP) in Taiwan.
      The causative agents responsible for human borreliosis were clarified. METHODS:
      Serum samples and skin specimens were collected from 14 patients with suspected
      PP and five controls. Serological testing by Western immunoblot analysis and
      isolation of Borrelia spirochetes from skin specimens were used to verify the
      Borrelia infection. Genetic identities of isolated spirochetes were determined by
      analyzing the gene sequences amplified by PCR assay based on the 5S (rrf)-23S
      (rrl) intergenic spacer amplicon gene of Borrelia burgdorferi sensu lato.
      RESULTS: Borrelia spirochetes were isolated from skin biopsies of three patients.
      Serological evidence of Borrelia infection in these patients was also confirmed
      by elevated IgG and IgM antibodies against the major protein antigens of B.
      burgdorferi. Phylogenetic analysis revealed that these detected spirochetes are
      genetically affiliated to the genospecies of Borrelia garinii and Borrelia
      afzelii with high sequence homology within the genospecies of B. garinii (91.0
      98.7%) and B. afzelii (97%). CONCLUSIONS: This study provides the first evidence
      of B. garinii and B. afzelii isolated and identified in patients with PP. Whether
      this unusual skin lesion is a new manifestation of Lyme disease needs to be
      studied further.

PMID- 24103334
TI  - Spatio-temporal analysis of Salmonella surveillance data in Thailand.
AB  - This study evaluates the usefulness of spatio-temporal statistical tools to
      detect outbreaks using routine surveillance data where limited epidemiological
      information is available. A dataset from 2002 to 2007 containing information
      regarding date, origin, source and serotype of 29,586 Salmonella isolates from
      Thailand was analysed. Data was grouped into human and non-human categories and
      the analysis was performed for the top five occurring serovars for each year of
      the study period. A total 91 human and 39 non-human significant spatio-temporal
      clusters were observed, accounting for 11% and 16% of the isolates, respectively.
      Serovar-specific associations between human and non-human clusters were also
      evaluated. Results show that these statistical tools can provide information for
      use in outbreak prevention and detection, in countries where only limited data is
      available. Moreover, it is suggested that monitoring non-human reservoirs can be
      relevant in predicting future Salmonella human cases.

PMID- 24103335
TI  - Social media in public health.
AB  - INTRODUCTION OR BACKGROUND: While social media interactions are currently not
      fully understood, as individual health behaviors and outcomes are shared online,
      social media offers an increasingly clear picture of the dynamics of these
      processes. SOURCES OF DATA: Social media is becoming an increasingly common
      platform among clinicians and public health officials to share information with
      the public, track or predict diseases. AREAS OF AGREEMENT: Social media can be
      used for engaging the public and communicating key public health interventions,
      while providing an important tool for public health surveillance. AREAS OF
      CONTROVERSY: Social media has advantages over traditional public health
      surveillance, as well as limitations, such as poor specificity, that warrant
      additional study. GROWING POINTS: Social media can provide timely, relevant and
      transparent information of public health importance; such as tracking or
      predicting the spread or severity of influenza, west nile virus or meningitis as
      they propagate in the community, and, in identifying disease outbreaks or
      clusters of chronic illnesses. AREAS TIMELY FOR DEVELOPING RESEARCH: Further work
      is needed on social media as a valid data source for detecting or predicting
      diseases or conditions. Also, whether or not it is an effective tool for
      communicating key public health messages and engaging both, the general public
      and policy-makers.

PMID- 24103336
TI  - Comparative analyses of mitochondrial and nuclear genetic markers for the
      molecular identification of Rhipicephalus spp.
AB  - The genus Rhipicephalus (Acari: Ixodidae) comprises a large number of vectors of
      pathogens of substantial medical and veterinary concern; however, species
      identification based solely on morphological features is often challenging. In
      the present study, genetic distance within selected Rhipicephalus species (i.e.,
      Rhipicephalus bursa, Rhipicephalus guilhoni, Rhipicephalus muhsamae,
      Rhipicephalus sanguineus sensu lato and Rhipicephalus turanicus), were
      investigated based on molecular and phylogenetic analyses of fragments of the
      mitochondrial 16S, 12S and cytochrome c oxidase subunit 1 (cox1) genes, as well
      as of the whole sequences of the ribosomal internal transcribed spacer-2 (ITS-2)
      region. Mean values of inter-specific genetic distance (e.g., up to 12.6%, 11.1%
      and 15.2%), as well as of intra-specific genetic distance (e.g., 0.9%, 0.9% and
      1%), calculated using the Kimura-2 parameter substitution model with uniform
      rates among sites for 16S, 12S and cox1 genes, respectively, confirmed the
      differentiation of the rhipicephaline species herein examined. The molecular
      identification was also supported by the distinct separation of species-specific
      clades inferred from the phylogenetic analyses of all mitochondrial sequences.
      Conversely, little interspecific divergence was detected amongst ribosomal ITS-2
      sequences (i.e., up to 2.8%) for species belonging to the R. sanguineus complex,
      which resulted in the ambiguous placement of selected R. sanguineus s.l. and R.
      turanicus sequences in the corresponding phylogenetic tree. Results from this
      study confirm the suitability of mtDNA markers for the reliable identification of
      ticks within the Rhipicephalus genus and provide a framework for future studies
      of taxonomy, speciation history and evolution of this group of ticks. 

PMID- 24103337
TI  - Rapamycin prevents drug seeking via disrupting reconsolidation of reward memory
      in rats.
AB  - The maladaptive drug memory developed between the drug-rewarding effect and
      environmental cues contributes to difficulty in preventing drug relapse.
      Established reward memories can be disrupted by pharmacologic interventions
      following their reactivation. Rapamycin, an inhibitor of mammalian target of
      rapamycin (mTOR) kinase, has been proved to be involved in various memory
      consolidation. However, it is less well characterized in drug memory
      reconsolidation. Using a conditioned place preference (CPP) procedure, we
      examined the effects of systemically administered rapamycin on reconsolidation of
      drug memory in rats. We found that systemically administered rapamycin (0.1 or 10
      mg/kg, i.p.) after re-exposure to drug-paired environment, dose dependently
      decreased the expression of CPP 1 d later, and the effect lasted for up to 14 d
      and could not be reversed by a priming injection of morphine. The effect of
      rapamycin on morphine-associated memory was specific to drug-paired context, and
      rapamycin had no effect on subsequent CPP expression when rats were exposed to
      saline-paired context or homecage. These results indicated that systemic
      administration of rapamycin after memory reactivation can persistently inhibit
      the drug seeking behaviour via disruption of morphine memory reconsolidation in
      rats. Additionally, the effect of rapamycin on memory reconsolidation was
      reproduced in cocaine CPP and alcohol CPP. Furthermore, rapamycin did not induce
      conditioned place aversion and had no effect on locomotor activity and anxiety
      behaviour. These findings suggest that rapamycin could erase the acquired drug
      CPP in rats, and that mTOR activity plays an important role in drug
      reconsolidation and is required for drug relapse. 

PMID- 24103338
TI  - [Inherited retinal dystrophies: contributions of molecular genetics].
AB  - Inherited retinal dystrophies are Mendelian neurodegenerative conditions. The
      mutations of the responsible genes lead both to cell dysfunction and cell death
      in the retina. The majority of these diseases are responsible for a progressive
      vision loss ending in almost complete blindness. Recent breakthroughs in
      molecular genetics technologies (microchips, next generation sequencing) resulted
      in a much better understanding of these conditions. Their genetic heterogeneity
      is extremely large, with 191 causal genes disclosed today, knowing that this
      number will increase in the next years as a significant proportion of cases,
      especially those with retinitis pigmentosa, do not have mutations in the
      currently identified genes. A single phenotype is often caused by mutations in
      several different genes. In addition, exhaustive gene knowledge led to recognize
      gene-specific clinical features found in several different phenotypes and thus to
      propose a pathophysiological hypothesis available for experimental testing.
      Importantly, this vast field of knowledge opens the way to pre-clinical and
      clinical therapeutic trials, currently increasing exponentially, and eagerly
      awaited by the patients for whom the only issue until now was ineluctable
      blindness. 

PMID- 24103339
TI  - [Glaucoma today: detection and therapeutic progress].
AB  - Second leading cause of blindness worldwide, glaucoma is an optic neuropathy
      related mainly but not exclusively to an increase of intraocular pressure. Angle
      closure glaucoma is related to a blockade of aqueous humor to the trabecular
      meshwork, whereas open-angle glaucoma is a degeneration of the trabecular
      meshwork, the filter that allows aqueous outflow from the eye. Many improvements
      have been made in terms of diagnosis, follow-up and treatments, although the
      treatment of glaucoma is restricted to control intraocular pressure, in order to
      prevent optic nerve degeneration or to stop the progression of the disease toward
      blindness. The first line therapy is based on topical medications that are
      administered for the whole life span. Although globally efficient, these
      treatments, and most likely the preservative included in the excipient to prevent
      bottle contamination, induce side effects in the long-term that may impair the
      quality of life, patient compliance or directly induce ocular surface changes
      like inflammatory cytokine release, or tear film destruction, with further dry
      eye disease and chronic inflammation. A large body of evidence has been
      accumulated, showing that benzalkonium chloride, the preservative mainly used, is
      toxic over the long run and plays a role in such ocular surface impairment.
      Therefore efforts have been made in the last decade to eliminate or replace this
      compound, providing safer therapies to the patients. Furthermore, the
      identification of chemokines as playing a role in the trabecular degeneration has
      open new directions for treating glaucoma. The blockade of one receptor of CXCL12
      has been experimentally shown not only to decrease intraocular pressure but also
      to prevent trabecular cell degeneration. This is an innovative concept that could
      allow development of new treatments, more specifically targeting the disease at
      its onset, rather than attempting to reduce its progression in its later stages. 

PMID- 24103340
TI  - [Darwin or Lamarck? Understanding the ocular surface and its normal or abnormal
      differentiation in order to cure ocular surface destruction with corneal
      opacification].
AB  - According to the World Health Organization, 5.1% of blindnesses or visual
      impairments are related to corneal opacification. Cornea is a transparent tissue
      placed in front of the color of the eye. Its transparency is mandatory for
      vision. The ocular surface is a functional unit including the cornea and all the
      elements involved in maintaining its transparency i.e., the eyelids, the
      conjunctiva, the lymphoid tissue of the conjunctiva, the limbus, the lacrymal
      glands and the tear film. The destruction of the ocular surface is a disease
      caused by : traumatisms, infections, chronic inflammations, cancers, toxics,
      unknown causes or congenital abnormalities. The treatment of the ocular surface
      destruction requires a global strategy including all the elements that are
      involved in its physiology. The microenvironnement of the ocular surface must
      first be restored, i.e., the lids, the conjunctiva, the limbus and the structures
      that secrete the different layers of the tear film. In a second step, the
      transparency of the cornea can be reconstructed. A corneal graft performed in a
      healthy ocular surface microenvironnement will have a better survival rate. To
      achieve these goals, a thorough understanding of the renewal of the epitheliums
      and the role of the epithelial stem cells are mandatory. 

PMID- 24103341
TI  - [Retinitis pigmentosa: eye sight restoration by optogenetic therapy].
AB  - Retinitis pigmentosa (RP) is a hereditary retinal disease leading to blindness,
      which affects two million people worldwide. Restoring vision in these blind
      patients was proposed by gene delivery of microbial light-activated ionic
      channels or pumps "optogenetic proteins" to transform surviving cells into
      artificial photoreceptors. This therapeutic strategy was validated in blind
      animal models of RP by recording at the level of the retina and cortex and by
      behavioural tests. The translational potentials of these optogenetic approaches
      have been evaluated using in vitro studies on post-mortem human retinal tissues.
      Here, we review these recent results and discuss the potential clinical
      applications of the optogenetic therapy for RP patients. 

PMID- 24103342
TI  - [Restoring vision in blind patients following photoreceptor degeneration:
      clinical results and future challenges].
AB  - Retinal prostheses aim at restoring vision in patients blind from photoreceptor
      degeneration by electrically stimulating the residual retinal tissue. Currently,
      the most efficient implants are either inserted in the subretinal space or on the
      vitreal side of the retina (epi-retinal). Although the residual tissue can partly
      degenerate, it was shown that acute stimulation of residual neurones can induce
      visual percepts. Recently, a clinical trial with the epiretinal Argus2 device (60
      electrodes) from the company 2nd Sight enabled most patients to orient and find
      light targets, some even reading words. This device has received a CE mark.
      Surprisingly, when the subretinal implant from the company Retina Implant AG
      displaying many more electrodes (1500 electrodes) was evaluated in clinical
      trials, the patient visual performances were fairly similar. The restored visual
      performances of the patients demonstrate that blind patients can recover some
      visual function when their residual retina is properly stimulated. However, the
      resolution is not yet sufficient to perform complex tasks such as autonomous
      locomotion, face identification or text reading. Several challenges remain to
      generate an increase in pixel density corresponding to the increase in electrode
      number and density. These challenges include the stimulation modality, the
      tissue/implant interface design, the electrode materials, and the visual
      information encoder. This review will discuss these great challenges after
      introducing the major clinical results.

PMID- 24103343
TI  - [Temporal regulation of abscission, the last step of cell division].
AB  - Cell division is one of the most tightly controlled steps of the cell cycle.
      Indeed, the many steps of cell division have to be perfectly coordinated both in
      time and space in order to ensure an error-free division and an accurate
      transmission of the genome from the mother cell to the two daughter cells.
      Abscission, the last step of cytokinesis, consists in the severing of the
      intercellular bridge that connects the two daughter cells after the contraction
      of the acto-myosin ring. As is the case for any other step of cell division,
      abscission has to be precisely regulated in order to take place at the right time
      and the proper place. Whereas the spatial regulation of abscission is quite well
      understood, the study of temporal regulation is in its infancy. This review
      begins by describing the formation of the intercellular bridge, its organization,
      and its composition. Next the different models of abscission are discussed.
      Finally, the current understanding of the temporal regulation of abscission is
      detailed. In particular, I present my recent results on the role of forces
      exerted by the daughter cells on the intercellular bridge. 

PMID- 24103345
TI  - Active case detection for malaria elimination: a survey among Asia Pacific
      countries.
AB  - BACKGROUND: Moving from malaria control to elimination requires national malaria
      control programmes to implement strategies to detect both symptomatic and
      asymptomatic cases in the community. In order to do this, malaria elimination
      programmes follow up malaria cases reported by health facilities to carry out
      case investigations that will determine the origin of the infection, whether it
      has been imported or is due to local malaria transmission. If necessary, the
      malaria programme will also carry out active surveillance to find additional
      malaria cases in the locality to prevent further transmission. To understand
      current practices and share information on malaria elimination strategies, a
      survey specifically addressing country policies on case investigation and
      reactive case detection was carried out among fourteen countries of the Asia
      Pacific Malaria Elimination Network (APMEN). METHODS: A questionnaire was
      distributed to the malaria control programme managers amongst 14 countries in the
      Asia Pacific who have national or sub-national malaria elimination goals.
      RESULTS: Results indicate that there are a wide variety of case investigation and
      active case detection activities employed by the 13 countries that responded to
      the survey. All respondents report conducting case investigation as part of
      surveillance activities. More than half of these countries conduct investigations
      for each case. Over half aim to accomplish the investigation within one to two
      days of a case report. Programmes collect a broad array of demographic data
      during investigation procedures and definitions for imported cases are varied
      across respondents. Some countries report intra-national (from a different
      province or district) importation while others report only international
      importation (from a different country). Reactive case detection in respondent
      countries is defined as screening households within a pre-determined radius in
      order to identify other locally acquired infections, whether symptomatic or
      asymptomatic. Respondents report that reactive case detection can be triggered in
      different ways, in some cases with only a single case report and in others if a
      defined threshold of multiple cases occurs. The spatial range of screening
      conducted varies from a certain number of households to an entire administrative
      unit (e g, village). Some countries target symptomatic people whereas others
      target all people in order to detect asymptomatic infections. The majority of
      respondent programmes collect a range of information from those screened for
      malaria, similar to the range of information collected during case investigation.
      CONCLUSION: Case investigation and reactive case detection are implemented in the
      malaria elimination programmes in the Asia Pacific, however practices vary widely
      from country to country. There is little evidence available to support countries
      in deciding which methods to maintain, change or adopt for improved effectiveness
      and efficiency. The development and use of common evaluation metrics for these
      activities will allow malaria programmes to assess performance and results of
      resource-intensive surveillance measures and may benefit other countries that are
      considering implementing these activities.

PMID- 24103346
TI  - Azathioprine-induced neuro-psychiatric disorders.

PMID- 24103347
TI  - Phthalates in German daycare centers: occurrence in air and dust and the
      excretion of their metabolites by children (LUPE 3).
AB  - Phthalates have been used for decades in large quantities, leading to the
      ubiquitous exposure of the population. In an investigation of 63 German daycare
      centers, indoor air and dust samples were analyzed for the presence of 10
      phthalate diesters. Moreover, 10 primary and secondary phthalate metabolites were
      quantified in urine samples from 663 children attending these facilities. In
      addition, the urine specimens of 150 children were collected after the weekend
      and before they went to daycare centers. Di-isobutyl phthalate (DiBP), dibutyl
      phthalate (DnBP), and di-2-ethylhexyl phthalate (DEHP) were found in the indoor
      air, with median values of 468, 227, and 194ng/m(3), respectively. In the dust,
      median values of 888mg/kg for DEHP and 302mg/kg for di-isononyl phthalate (DiNP)
      were observed. DnBP and DiBP were together responsible for 55% of the total
      phthalate concentration in the indoor air, whereas DEHP and DiNP were responsible
      for 70% and 24% of the total phthalate concentration in the dust. Median
      concentrations in the urine specimens were 44.7MUg/l for the DiBP monoester,
      32.4MUg/l for the DnBP monoester, and 16.5MUg/l and 17.9MUg/l for the two
      secondary DEHP metabolites. For some phthalates, we observed significant
      correlations between their concentrations in the indoor air and dust and their
      corresponding metabolites in the urine specimens using bivariate analyses. In
      multivariate analyses, the concentrations in dust were not associated with
      urinary metabolite excretion after controlling for the concentrations in the
      indoor air. The total daily "high" intake levels based on the 95th percentiles
      calculated from the biomonitoring data were 14.1MUg/kg b.w. for DiNP and
      11.9MUg/kg b.w. for DEHP. Compared with tolerable daily intake (TDI) values, our
      "high" intake was 62% of the TDI value for DiBP, 49% for DnBP, 24% for DEHP, and
      9% for DiNP. For DiBP, the total daily intake exceeded the TDI value for 2.4% of
      the individuals. Using a cumulative risk-assessment approach for the sum of DEHP,
      DnBP, and DiBP, 20% of the children had concentrations exceeding the hazard index
      of one. Therefore, a further reduction of the phthalate exposure of children is
      needed. 

PMID- 24103348
TI  - Estimation of internal exposure of the thyroid to (131)I on the basis of (134)Cs
      accumulated in the body among evacuees of the Fukushima Daiichi Nuclear Power
      Station accident.
AB  - Namie Town was heavily contaminated by the Fukushima Daiichi Nuclear Power
      Station accident. The thyroid equivalent dose for residents who lived in Namie
      was estimated using results of whole body counting examinations which were
      carried out by the Japan Atomic Energy Agency a few months after the nuclear
      accident. Photon peaks of (131)I and (134)Cs were previously measured by the
      authors using a NaI(Tl) scintillation spectrometer and that information was used
      to estimate the (131)I/(134)Cs activity ratio of total intake in the present
      study. The maximum values of (131)I/(134)Cs activity ratio corresponding to
      thyroid uptake factors of 0.3, 0.1 and 0.03 were evaluated to be 0.9, 2.6 and
      8.7, respectively. The maximum value of the (131)I/(134)Cs activity ratio was
      used to obtain the most conservative thyroid equivalent dose estimation. The
      maximum internal exposure of the thyroid to (131)I on the basis of (134)Cs
      accumulated in the body measured by the whole body counter was estimated to be
      18mSv. This value was much smaller than 50mSv that the International Atomic
      Energy Agency recommends as the dose at which exposed persons should take stable
      iodine tablets. 

PMID- 24103349
TI  - Effect of ambient temperature and air pollutants on the risk of preterm birth,
      Rome 2001-2010.
AB  - INTRODUCTION: Although the prevalence of preterm births ranges from 5 to 13% and
      represents the leading cause of perinatal mortality and morbidity in developed
      countries, the etiology of preterm birth remains uncertain. We aimed to evaluate
      the effect of short-term exposure to high and low temperatures and air pollution
      on preterm delivery and to identify socio-demographic and clinical maternal risk
      factors enhancing individual susceptibility. METHODS: We analyzed all singleton
      live births by natural delivery that occurred in Rome in 2001-2010. A time-series
      approach was used to estimate the effect of exposure to minimum temperature,
      maximum apparent temperature, heat waves, particulate matter with an aerodynamic
      diameter of 10MUm or less (PM10), ozone, and nitrogen dioxide in the month
      preceding delivery; the analysis was conducted separately for cold and warm
      seasons. Socio-demographic and clinical risk factors were included as interaction
      terms. RESULTS: Preterm births comprised nearly 6% of our cohort. An increase of
      1.9% (95% confidence interval (CI) 0.86-2.87) in daily preterm births per 1
      degrees C increase in maximum apparent temperature in the 2days preceding
      delivery was estimated for the warm season. Older women, women with higher
      education levels, and women with obstetric or chronic pathologies reported during
      delivery had a lower effect of temperature on the risk of preterm birth, while
      women with a chronic disease in the two years before delivery and mothers<20years
      showed a higher effect. A +19% (95% CI 7.91-31.69) increase in preterm births was
      observed during heat waves. Temperature had no effect during the cold season. We
      detected a significant effect of PM10 on preterm-birth risk at a lag period of 12
      22days during the warm season (+0.69%; 95% CI 0.23-1.15, for 1MUg/m(3) increase
      of pollutant); women with obstetric pathologies and with a higher education level
      showed a higher risk. CONCLUSIONS: Our results suggest a possible short-term
      effect of heat and a more delayed and prolonged effect of PM10 exposure on
      preterm-birth risk, as well as the existence of more susceptible subgroups of
      women. Our observations support the few reported investigations, and may help to
      increase awareness among public-health stakeholders and clinicians regarding the
      role of these environmental exposures as risk factors for premature birth and
      health consequences for children later in life.

PMID- 24103350
TI  - Biomonitoring of the general population living near a modern solid waste
      incinerator: a pilot study in Modena, Italy.
AB  - BACKGROUND AND GOALS: As part of the authorization process for the solid waste
      incinerator (SWI) in Modena, Italy, a human biomonitoring cross-sectional pilot
      study was conducted to investigate the degree to which people living and working
      in the proximity of the plant were exposed to SWI emissions. METHODS: Between May
      and June 2010, 65 subjects living and working within 4km of the incinerator
      (exposed) and 103 subjects living and working outside this area (unexposed) were
      enrolled in the study. Blood, serum and urinary metals (Pb, Cd, Cu, Zn, Hg, Mn,
      Ni), urinary benzene, toluene, xylene (BTEX), S-phenylmercapturic acid (SPMA),
      and urinary polycyclic aromatic hydrocarbons (PAHs) were analysed. Information
      about lifestyle, anthropometric characteristics, residence, and health status was
      collected by a self-administered questionnaire. Exposure to particulate matter
      (PM) emitted from the SWI was estimated using fall-out maps from a quasi-Gaussian
      dispersion model. A multiple linear regression analysis investigated the
      relationship between biomarkers and the distance of a subject's place of
      residence from the SWI plant or the exposure to PM. RESULTS: Urinary BTEX and
      SPMA and blood, serum and urinary metals showed no differences between exposed
      and unexposed subjects. PAHs were higher in exposed than in unexposed subjects
      for phenanthrene, anthracene, and pyrene (median levels: 9.5 vs. 7.2ng/L, 0.8 vs.
      <0.5ng/L and 1.6 vs. 1.3ng/L, respectively, p<0.05). Multiple linear regression
      analysis showed that blood Cd and Hg and urinary Mn, fluorene, phenanthrene,
      anthracene and pyrene were inversely correlated to the distance of a subject's
      residence from the SWI. Urinary Mn, fluorene and phenanthrene were directly
      correlated to PM exposure. CONCLUSIONS: This study, although not representative
      of the general population, suggests that specific biomarkers may provide
      information about the degree of exposure the subjects working and living in the
      proximity of the SWI plant may have to emissions from that facility.

PMID- 24103351
TI  - Ethnicity and suicide attempt: analysis in bipolar disorder and schizophrenia.
AB  - BACKGROUND: Evidence is mixed as to whether White Europeans are at a higher risk
      for suicide attempts or completions compared to other ethnic groups. The present
      analysis assessed whether risk for suicide attempt was associated with White
      European ethnicity in 907 subjects with schizophrenia or bipolar disorder.
      METHODS: Subjects were diagnosed using the Structured Clinical Interview for DSM
      IV, and ethnicity was determined by self-report. Subjects were recruited from
      psychiatric care centers in Toronto, Canada. Logistic regression correcting for
      clinical covariates like age, gender and diagnosis, was used in this study.
      RESULTS: We found no difference in suicide attempter status in white and non
      white subjects who were diagnosed with schizophrenia and bipolar disorder.
      CONCLUSION: Our study does not support the evidence that White-European patients
      in North America are at higher risk for suicide attempt compared to non-European
      descent subjects. However, this result has to be replicated in larger studies in
      patients with these disorders.

PMID- 24103352
TI  - Validity, intra- and inter-observer reliability of automated devices for the
      assessment of ankle brachial index using photo-plethysmography.
AB  - BACKGROUND: Ankle-brachial-Index (ABI) measured by manual Dopplersonography is an
      easily assessable marker of global cardiovascular risk. The aim of this study was
      to establish novel photo-plethysmography (PPG)-based ABI assessments in an
      epidemiologic context and to compare its results with those of Doppler. METHODS:
      Two devices for PPG-based ABI assessments (Vicorder, Vascular Explorer) were
      tested and compared against Doppler in 56 putatively healthy subjects. We
      determined acceptance, time requirements, agreement of repeat measurements,
      agreement with Doppler and intra- and inter-observer concordances for both
      devices and compared the results. Differences between cuff inflation- and
      deflation-based methods were also studied for Vascular Explorer. RESULTS:
      Acceptance was similar for both devices but Vascular Explorer was more time
      consuming. Agreement of multiple measurements was moderate for both methods
      highlighting the importance of measurement replicates. Both automated devices
      showed significantly higher ABI compared to Doppler which can be traced back to
      higher brachial pressures (Vicorder) or higher ankle pressures (Vascular
      Explorer). This effect is more pronounced for Vascular Explorer but can be
      ameliorated using the deflation method of measurement. Intra-observer
      concordances were similar. Inter-observer concordance was non-significantly
      better for Vicorder. CONCLUSIONS: Both devices proved to be feasible in
      epidemiologic studies, but compared to Doppler, do not constitute an advantage
      regarding time requirement and accuracy of ABI assessment. Since PPG-based ABI
      values are inflated compared to Doppler, it will be necessary to adjust Doppler
      based cut-offs for risk stratification.

PMID- 24103353
TI  - Seroepidemiology of pertussis in a cross-sectional study of an adult general
      population in Denmark.
AB  - An increase in pertussis has been observed in several countries over the last
      decades, especially in adult populations. The seroprevalence of pertussis was
      determined in a cross-sectional study of the adult population in the Copenhagen
      area, Denmark, conducted between 2006 and 2008. Specific IgG antibodies against
      pertussis toxin (PT) were measured in 3440 persons resulting in an age
      standardized seroprevalence of 3.0% (95% confidence interval 1.9-4.7) using an
      IgG anti-PT cut-off of 75 IU/ml. By using antibody decay profiles from
      longitudinal data the estimated seroincidence was 143/1000 person-years. In
      contrast, an incidence of 0.03/1000 person-years was estimated from the official
      data of notified cases during the same period. Of the investigated risk factors,
      only age and education were significantly associated with pertussis infection.
      This study indicates that pertussis is highly underestimated in the adult
      population in Denmark, which has implications for future prevention strategies,
      including raising the awareness of pertussis.

PMID- 24103355
TI  - The use of MR imaging to detect residual versus recurrent nasopharyngeal
      carcinoma following treatment with radiation therapy.
AB  - OBJECTIVE: Residual tumor and fibrosis are commonly observed with magnetic
      resonance (MR) imaging following radiotherapy for nasopharyngeal carcinoma (NPC).
      Therefore, MR images of NPC following treatment with radiotherapy were
      retrospectively analyzed to evaluate whether post-radiation changes associated
      with residual tumors, recurrent tumors, and fibrosis could be distinguished 1
      month and 3-6 months after treatment. METHODS: MR images were analyzed for 108
      patients who completed radiotherapy for NPC and underwent 5-years of follow-up.
      The presence and incidence of residual tumor versus fibrosis was evaluated and
      compared with 5-year tumor recurrence rates. RESULTS: Residual tumors were
      detected in 54/108 (50.0%) patients 1 month after radiotherapy, and in 18/108
      (16.7%) patients 3-6 months after radiotherapy. Fibrosis was only detected in
      59/108 (54.6%) patients 3-6 months after radiotherapy. After 5 years, tumor
      recurrence occurred in 13/108 (12%) patients, with the average interval between
      tumor recurrence and the completion of radiotherapy being 29.15 months. In
      addition, the 1-, 2-, 3-, 4-, and 5-year relapse rates were 1.9%, 5.6%, 9.3%,
      11.1%, and 12.0%, respectively. Based on the images analyzed, significant
      differences in tumor recurrence and residual tumor rate (P = 0.038), and between
      tumor recurrence and fibrosis (P = 0.021), were observed 1 month and 3-6 months
      after radiotherapy, respectively. CONCLUSIONS: In this cohort, tumor recurrence
      was detected 2-3 year after irradiation and a strong correlation between 5-year
      recurrence rate and detection of residual tumor or fibrosis by MRI up to six
      months after radiotherapy was observed.

PMID- 24103354
TI  - Characterization of the enhancing lesions on dynamic contrast enhanced magnetic
      resonance imaging in patients with interstitial mammoplasty.
AB  - PURPOSE: The purpose of this study was to categorize the morphologic and kinetic
      features of enhancing lesions in breasts with interstitial mammoplasty using
      dynamic contrast-enhanced magnetic resonance imaging and to assess factors
      predictive of breast cancer. MATERIALS AND METHODS: We retrospectively reviewed
      the clinical and radiological data of 21 enhancing lesions in 19 patients with
      interstitial mammoplasty, who underwent breast magnetic resonance imaging and
      biopsy or an operation in our hospital from September 2008 to July 2012. These
      lesions were sorted by morphological and kinetic features and final assessment
      category according to the BI-RADS lexicon. RESULTS: Nine cases were confirmed to
      be ductal carcinoma in situ (n = 2) and invasive ductal carcinoma (n = 7), and
      the remaining 12 cases were fibrocystic disease (n = 2), fibroadenoma (n = 2),
      fat necrosis (n = 1), foreign body granuloma (n = 3) and silicone mastitis (n =
      1). Common features of malignancy included irregular shape (50.0%), spiculated
      margins (75.0%), heterogeneous enhancement (50.0%) and type III kinetic pattern
      (87.5%). The correlations of margins and kinetic curve pattern with benignity and
      malignancy approached statistical significance (p = 0.02, respectively). We found
      no correlation for shape (p = 0.33) or internal enhancement (p = 0.42) between
      lesion types. The malignancy rate of enhancing lesions was 42.8% (9/21). The
      sensitivity and specificity of dynamic contrast-enhanced magnetic resonance
      imaging were 100% and 16.67%, respectively. The positive predictive value,
      negative predictive value and accuracy of magnetic resonance imaging were 47.38%,
      100% and 52.38%. Overall inter-observer agreement for the kinetic curve pattern
      was good (kappa = 0.67). Moderate agreement was seen in describing the shape,
      margin, enhancement and assessing the final category (kappa = 0.59, 0.46, 0.58
      and 0.49, respectively). CONCLUSION: Dynamic contrast-enhanced magnetic resonance
      imaging had a high sensitivity, negative predictive value for the prediction of
      breast cancer but a low specificity due to features of foreign body-related
      lesions that mimicked malignant lesions. The significant predictive factors for
      malignancy were margins, kinetic curve pattern and final assessment category.
      Overall inter-observer agreement for the kinetic curve pattern was good.

PMID- 24103356
TI  - Comparison of 3D TOF-MRA and 3D CE-MRA at 3T for imaging of intracranial
      aneurysms.
AB  - PURPOSE: To compare 3T elliptical-centric CE MRA with 3T TOF MRA for the
      detection and characterization of unruptured intracranial aneurysms (UIAs), by
      using digital subtracted angiography (DSA) as reference. MATERIALS AND METHODS:
      Twenty-nine patients (12 male, 17 female; mean age: 62 years) with 41 aneurysms
      (34 saccular, 7 fusiform; mean diameter: 8.85 mm [range 2.0-26.4mm]) were
      evaluated with MRA at 3T each underwent 3D TOF-MRA examination without contrast
      and then a 3D contrast-enhanced (CE-MRA) examination with 0.1mmol/kg bodyweight
      gadobenate dimeglumine and k-space elliptic mapping (Contrast ENhanced Timing
      Robust Angiography [CENTRA]). Both TOF and CE-MRA images were used to evaluate
      morphologic features that impact the risk of rupture and the selection of a
      treatment. Almost half (20/41) of UIAs were located in the internal carotid
      artery, 7 in the anterior communicating artery, 9 in the middle cerebral artery
      and 4 in the vertebro-basilar arterial system. All patients also underwent DSA
      before or after the MR examination. RESULTS: The CE-MRA results were in all cases
      consistent with the DSA dataset. No differences were noted between 3D TOF-MRA and
      CE-MRA concerning the detection and location of the 41 aneurysms or visualization
      of the parental artery. Differences were apparent concerning the visualization of
      morphologic features, especially for large aneurysms (>13 mm). An irregular sac
      shape was demonstrated for 21 aneurysms on CE-MRA but only 13/21 aneurysms on 3D
      TOF-MRA. Likewise, CE-MRA permitted visualization of an aneurismal neck and
      calculation of the sac/neck ratio for all 34 aneurysms with a neck demonstrated
      at DSA. Conversely, a neck was visible for only 24/34 aneurysms at 3D TOF-MRA. 3D
      CE-MRA detected 15 aneurysms with branches originating from the sac and/or neck,
      whereas branches were recognized in only 12/15 aneurysms at 3D TOF-MRA.
      CONCLUSION: For evaluation of intracranial aneurysms at 3T, 3D CE-MRA is superior
      to 3D TOF-MRA for assessment of sac shape, detection of aneurysmal neck, and
      visualization of branches originating from the sac or neck itself, if the size of
      the aneurysm is greater than 13 mm. 3T 3D CE-MRA is as accurate and effective as
      DSA for the evaluation of UIAs.

PMID- 24103358
TI  - Discovery of a low-glycaemic index potato and relationship with starch digestion
      in vitro.
AB  - Potatoes are usually a high-glycaemic index (GI) food. Finding a low-GI potato
      and developing a screening method for finding low-GI cultivars are both health
      and agricultural priorities. The aims of the present study were to screen the
      commonly used and newly introduced cultivars of potatoes, in a bid to discover a
      low-GI potato, and to describe the relationship between in vitro starch
      digestibility of cooked potatoes and their in vivo glycaemic response. According
      to International Standard Organisation (ISO) guidelines, seven different potato
      cultivars were tested for their GI. In vitro enzymatic starch hydrolysis and
      chemical analyses, including amylose content analysis, were carried out for each
      potato cultivar, and correlations with the respective GI values were sought. The
      potato cultivars had a wide range of GI values (53-103). The Carisma cultivar was
      classified as low GI and the Nicola cultivar (GI = 69) as medium GI and the other
      five cultivars were classified as high GI according to ISO guidelines. The GI
      values were strongly and positively correlated with the percentage of in vitro
      enzymatic hydrolysis of starch in the cooked potatoes, particularly with the
      hydrolysis percentage at 120 min (r 0.91 and P <0.01). Amylose, dietary fibre and
      total starch content was not correlated with either in vitro starch digestibility
      or GI. The findings suggest that low-GI potato cultivars can be identified by
      screening using a high-throughput in vitro digestion procedure, while chemical
      composition, including amylose and fibre content, is not indicative.

PMID- 24103357
TI  - Tristetraprolin expression and microRNA-mediated regulation during simian
      immunodeficiency virus infection of the central nervous system.
AB  - BACKGROUND: The RNA-binding protein tristetraprolin (TTP) participates in normal
      post-transcriptional control of cytokine and chemokine gene expression,
      dysregulation of which contributes to the HIV-associated neurocognitive
      disorders. Transcriptional and post-transcriptional regulation of TTP has been
      described, including regulation by microRNA-29a. In the simian immunodeficiency
      virus (SIV) model of HIV CNS disease, control of cytokine/chemokine expression
      coincides with the end of acute phase infection. This control is lost during
      progression to disease. In this study, we assessed TTP regulation and association
      with cytokine regulation in the brain during SIV infection. RESULTS: Quantitation
      of TTP expression over the course of SIV infection revealed downregulation of TTP
      during acute infection, maintenance of relatively low levels during asymptomatic
      phase, and increased expression only during late-stage CNS disease, particularly
      in association with severe disease. The ability of miR-29a to regulate TTP was
      confirmed, and evidence for additional miRNA targeters of TTP was found. However,
      increased miR-29a expression in brain was not found to be significantly
      negatively correlated with TTP. Similarly, increased TTP during late-stage
      disease was not associated with lower cytokine expression. CONCLUSIONS: TTP
      expression is regulated during SIV infection of the CNS. The lack of significant
      negative correlation of miR-29a and TTP expression levels suggests that while miR
      29a may contribute to TTP regulation, additional factors are involved. Reduced
      TTP expression during acute infection is consistent with increased cytokine
      production during this phase of infection, but the increases in TTP observed
      during late-stage infection were insufficient to halt runaway cytokine levels.
      While antisense inhibitors of the post-transcriptional targeters of TTP
      identified here could conceivably be used further to augment TTP regulation of
      cytokines, it is possible that high levels of TTP are undesirable. Additional
      research is needed to characterize members of the miRNA/TTP/cytokine regulatory
      network and identify nodes that may be best targeted therapeutically to
      ameliorate the effects of chronic inflammation in retrovirus-associated CNS
      disease.

PMID- 24103359
TI  - Development and validation of an electronic FFQ to assess food intake in the
      Slovene population.
AB  - OBJECTIVE: To develop and validate an electronic FFQ that estimates the food and
      nutrient intakes, especially fat intake, in a healthy, adult population from the
      coastal (Mediterranean) part of Slovenia. DESIGN: A new electronic FFQ was
      developed for a survey entitled 'A multidisciplinary approach in the treatment of
      obesity', conducted at the University of Primorska, and validated against a 3 d
      weighed food record (FR). SETTING: Coastal region of Slovenia. SUBJECTS: Our
      study population included eighty-five healthy adults aged 25-49 years, recruited
      from the local coastal region of Slovenia. Intakes of food groups, macronutrients
      and energy, estimated by the FR and the FFQ, were compared using correlation
      coefficients, cross-classification and Bland-Altman plots. RESULTS: The mean
      value of most nutrient intakes tended to be higher in the FFQ compared with the
      FR, except for carbohydrate, fibre and energy. Regression analysis demonstrated
      an acceptable agreement between the FFQ and FR. The FFQ was moderately correlated
      with the FR (0.30-0.54), and most of the correlations increased after energy
      adjustment and after de-attenuation. Relatively high (more than 70 %) proportions
      of participants were correctly classified into the same or an adjacent quartile.
      Bland-Altman analysis confirmed an acceptable level of agreement between the two
      methods. CONCLUSIONS: The electronic FFQ, developed for a healthy adult Slovene
      population from the coastal region, was shown to be a valid tool to assess food
      group and nutrient intakes, especially fat intakes, and to rank individuals by
      their intakes within gene-nutrient studies.

PMID- 24103360
TI  - Concordance between in vivo and postmortem measurements of cholinergic
      denervation in rats using PET with [18F]FEOBV and choline acetyltransferase
      immunochemistry.
AB  - BACKGROUND: Fluorine-18 fluoroethoxybenzovesamicol ([18F]FEOBV) is a radioligand
      for the selective imaging of the vesicular acetylcholine transporter with
      positron emission tomography (PET). The current study demonstrates that
      pathological cortical cholinergic deafferentation can be quantified in vivo with
      [18F]FEOBV PET, yielding analogous results to postmortem histological techniques.
      METHODS: Fifteen male rats (3 months old) underwent a cerebral infusion of 192
      IgG-saporin at the level of the nucleus basalis magnocellularis. They were
      scanned using [18F]FEOBV PET, then sacrificed, and their brain tissues collected
      for immunostaining and quantification of cholinergic denervation using optical
      density (OD). RESULTS: For both PET binding and postmortem OD, the highest losses
      were found in the cortical areas, with the highest reductions in the
      orbitofrontal, sensorimotor, and cingulate cortices. In addition, OD
      quantification in the affected areas accurately predicts [18F]FEOBV uptake in the
      same regions when regressed linearly. CONCLUSIONS: These findings support
      [18F]FEOBV as a reliable imaging agent for eventual use in human
      neurodegenerative conditions in which cholinergic losses are an important aspect.

PMID- 24103361
TI  - Salt drying: a low-cost, simple and efficient method for storing plants in the
      field and preserving biological repositories for DNA diversity research.
AB  - Although a variety of methods have been optimized for the collection and storage
      of plant specimens, most of these are not suited for field expeditions for a
      variety of logistic reasons. Drying specimens with silica gel in polyethylene
      bags is currently the standard for field-sampling methods that are suitable for
      subsequent DNA extraction. However, silica-gel repositories are not readily
      available in remote areas, and its use is not very cost-effective for the long
      term storage of collections or in developing countries with limited research
      budgets. Salting is an ancient and traditional drying process that preserves food
      samples by dehydrating tissues and inhibiting water-dependent cellular
      metabolism. We compared salt and silica-gel drying methods with respect to
      dehydration rates overtime, DNA quality and polymerase chain reaction(PCR)
      success to assess whether dry salting can be used as an effective plant
      preservation method for DNA analysis. Specimens from eleven plant species
      covering a variety of leaf structures, leaf thicknesses and water contents were
      analysed. Experimental work indicated that (i) levels of dehydration in sodium
      chloride were usually comparable to those obtained when silica gel was used, (ii)
      no spoilage, fungal or bacterial growth was observed for any of the species with
      all drying treatments and (iii) good yields of quality genomic DNA suitable for
      PCR applications were obtained in the salt-drying treatments. The preservation of
      plant tissues in commercial table salt appears to be a satisfactory, and
      versatile method that may be suitable in remote areas where cryogenic resources
      and silica repositories are not available. 

PMID- 24103362
TI  - Modelling and simulation of effect of ultrasonic vibrations on machining of
      Ti6Al4V.
AB  - The titanium alloys cause high machining heat generation and consequent rapid
      wear of cutting tool edges during machining. The ultrasonic assisted turning
      (UAT) has been found to be very effective in machining of various materials;
      especially in the machining of "difficult-to-cut" material like Ti6Al4V. The
      present work is a comprehensive study involving 2D FE transient simulation of UAT
      in DEFORM framework and their experimental characterization. The simulation shows
      that UAT reduces the stress level on cutting tool during machining as compared to
      that of in continuous turning (CT) barring the penetration stage, wherein both
      tools are subjected to identical stress levels. There is a 40-45% reduction in
      cutting forces and about 48% reduction in cutting temperature in UAT over that of
      in CT. However, the reduction magnitude reduces with an increase in the cutting
      speed. The experimental analysis of UAT process shows that the surface roughness
      in UAT is lower than in CT, and the UATed surfaces have matte finish as against
      the glossy finish on the CTed surfaces. Microstructural observations of the chips
      and machined surfaces in both processes reveal that the intensity of thermal
      softening and shear band formation is reduced in UAT over that of in CT. 

PMID- 24103363
TI  - Cancer patients' relatives' perspectives on disclosure of bad news to patients.

PMID- 24103364
TI  - Mapping of an ultrasonic bath for ultrasound assisted extraction of mangiferin
      from Mangifera indica leaves.
AB  - The present work deals with the mapping of an ultrasonic bath for the maximum
      extraction of mangiferin from Mangifera indica leaves. I3(-) liberation
      experiments (chemical transformations) and extraction (physical transformations)
      were carried out at different locations in an ultrasonic bath and compared. The
      experimental findings indicated a similar trend in variation in an ultrasonic
      bath by both these methods. Various parameters such as position and depth of
      vessel in an ultrasonic bath, diameter and shape of a vessel, frequency and input
      power which affect the extraction yield have been studied in detail. Maximum
      yield of mangiferin obtained was approximately 31 mg/g at optimized parameters:
      distance of 2.54 cm above the bottom of the bath, 7 cm diameter of vessel, flat
      bottom vessel, 6.35 cm liquid height, 122 W input power and 25 kHz frequency. The
      present work indicates that the position and depth of vessel in an ultrasonic
      bath, diameter and shape of a vessel, frequency and input power have significant
      effect on the extraction yield. This work can be used as a base for all
      ultrasonic baths to obtain maximum efficiency for ultrasound assisted extraction.

PMID- 24103365
TI  - An oxygen enrichment device for lowlanders ascending to high altitude.
AB  - BACKGROUND: When ascending to the high altitude, people living in low altitude
      areas will suffer from acute mountain sickness. The aim of this study is to test
      the hypothesis that whether an oxygen concentration membrane can be made and used
      to construct a new portable oxygen enrichment device for individuals in acute
      exposure to the high altitude. METHODS: The membrane was fabricated using
      vinylsiloxane rubber, polyphenylene oxide hydrogen silicone polymers,
      chloroplatinic acid and isopropyl alcohol. The membrane was assembled in a frame
      and the performance was tested in terms of concentration of oxygen, flow rate of
      oxygen enriched air, pressure ratio across the membrane and ambient temperature.
      Furthermore, the oxygen concentration device was constructed using the membrane,
      a DC fan, vacuum pump and gas buffer. A nonrandomized preliminary field test was
      conducted, in which eight healthy male subjects were flown to Tibet (Lhasa, 3,700
      m). First, subjects wore the oxygen enrichment device and performed an
      incremental exercise on cycle ergometer. The test included heart rate (HR),
      saturation of peripheral oxygen (SpO2) and physical work capacity (PWC). Then,
      after a rest period of 4 hours, the experimental protocol was repeated without
      oxygen enrichment device. RESULTS: The testing showed that the membrane could
      increase the oxygen concentration by up to 30%. Simulation test indicated that
      although the performance of the oxygen enrichment device decreased with
      altitudes, the oxygen concentration could still maintain 28% with flow rate of
      enriched air 110 cm3/s at 5000 m. The field test showed that higher SpO2, lower
      HR, and better PWC (measured by the PWC-170) were observed from all the subjects
      using oxygen enrichment device compared with non-using (P < 0.01). CONCLUSIONS:
      We concluded that the new portable oxygen enrichment device would be effective in
      improving exercise performance when ascending to the high altitude.

PMID- 24103366
TI  - Cu(II)-disulfide complexes display simultaneous superoxide dismutase- and
      catalase-like activities.
AB  - Superoxide is a potentially toxic by-product of cellular metabolism. We have
      addressed here the in vitro ability of complexes formed between copper(II) ions
      and various biologically-occurring disulfides (RSSR: oxidized glutathione,
      cystine, homocystine and alpha-lipoic acid) to react with superoxide. The studied
      complexes were found to react with superoxide (generated by a xanthine/xanthine
      oxidase system) at rate constants (kCu(II)-RSSR) close to 10(6)M(-1)s(-1), which
      are three orders of magnitude lower than that reported for superoxide dismutase
      (SOD) but comparable to that of several other copper-containing complexes
      reported as SOD mimetics. The interaction between the tested Cu(II)-RSSR and
      superoxide, led to the generation and recovery of concentrations of hydrogen
      peroxide and oxygen that were, respectively, below and above those theoretically
      expected from a sole SOD mimetic action. Interestingly, oxygen was generated when
      the Cu(II)-RSSR complexes were directly incubated with hydrogen peroxide. Taken
      together, these results reveal that the Cu(II)-RSSR complexes not only have the
      capacity to dismutate superoxide but also to simultaneously act like catalase
      mimetic molecules. When added to superoxide-overproducing mitochondria (condition
      attained by its exposure to diclofenac), three of the tested complexes were able
      (2-4MUM), not only to totally restore, but also to lower below the basal level
      the mitochondrial production of superoxide. The present study is first in
      reporting on the potential of Cu(II)-disulfide complexes to act as SOD and
      catalase like molecules, suggesting a potential for these types of molecules to
      act as such under physiological and/or oxidative-stress conditions. 

PMID- 24103367
TI  - Activation of alpha2 adrenoceptors inhibited NMDA receptor-mediated nociceptive
      transmission in spinal dorsal horn of mice with inflammatory pain.
AB  - The alpha2 adrenoceptor is highly enriched in spinal dorsal horn and involved in
      descending noradrenergic pain modification. Following peripheral tissue injury,
      intrathecal application of alpha2 adrenoceptor agonists effectively alleviates
      the pathological pain hypersensitivity, although the precise mechanisms are not
      fully understood. The present study induced inflammatory pain by intraplantar
      injection of Complete Freund's Adjuvant (CFA), and prepared the spinal cord
      slices to assay the possible influence of alpha2 adrenoceptor agonist clonidine
      on the synaptic transmission mediated by NMDA receptor (NMDAR), a critical player
      in spinal sensitization. Whole-cell patch clamp recordings in lamina II neurons
      illustrated that clonidine significantly decreased the amplitudes of NMDAR
      mediated monosynaptic responses in inflamed mice through activation of alpha2A
      subtype adrenoceptor. No significant alteration in the paired-pulse ratio before
      and after clonidine application indicated the postsynaptic origin. Intracellular
      loading of nonhydrolyzable GDP analog GDP-beta-S blocked, whereas direct
      inhibition of cAMP-dependent protein kinase (PKA) mimicked, the inhibitory effect
      of clonidine on NMDAR currents, implicating that Galphai protein/PKA signaling
      was involved in clonidine action. Biochemical analysis in vivo revealed that
      intrathecal clonidine administration specifically decreased the content of GluN2B
      subunit-containing NMDAR at synaptosomal membrane fraction, a result associated
      closely with the alleviation of inflammatory pain. Electrophysiological
      recordings in vitro further demonstrated that GluN2B receptor-selective inhibitor
      ifenprodil dramatically reduced NMDAR synaptic responses in inflamed mice and
      more importantly, occluded the synaptic inhibition produced by clonidine. These
      data suggested that the noradrenergic suppression of inflammatory pain might
      involve the blockade of GluN2B receptor-mediated nociceptive transmission in
      spinal dorsal horn.

PMID- 24103368
TI  - Pathogenesis of acute stroke and the role of inflammasomes.
AB  - Inflammation is an innate immune response to infection or tissue damage that is
      designed to limit harm to the host, but contributes significantly to ischemic
      brain injury following stroke. The inflammatory response is initiated by the
      detection of acute damage via extracellular and intracellular pattern recognition
      receptors, which respond to conserved microbial structures, termed pathogen
      associated molecular patterns or host-derived danger signals termed damage
      associated molecular patterns. Multi-protein complexes known as inflammasomes
      (e.g. containing NLRP1, NLRP2, NLRP3, NLRP6, NLRP7, NLRP12, NLRC4, AIM2 and/or
      Pyrin), then process these signals to trigger an effector response. Briefly,
      signaling through NLRP1 and NLRP3 inflammasomes produces cleaved caspase-1, which
      cleaves both pro-IL-1beta and pro-IL-18 into their biologically active mature pro
      inflammatory cytokines that are released into the extracellular environment. This
      review will describe the molecular structure, cellular signaling pathways and
      current evidence for inflammasome activation following cerebral ischemia, and the
      potential for future treatments for stroke that may involve targeting
      inflammasome formation or its products in the ischemic brain.

PMID- 24103369
TI  - Quantitative analysis of site-specific N-glycans on sera haptoglobin beta chain
      in liver diseases.
AB  - The site-specific characterization of N-glycans in glycoproteins with the
      potential of clinical application is important. In our previous report, the
      overall N-glycans of sera haptoglobin (Hp) beta chain were found to be different
      in liver diseases. Hp beta chain contains four potential sites of N
      glycosylation. In this study, we investigated the potential change of N-glycans
      on Hp beta chain in a site-specific fashion. Sera Hp beta chain in healthy
      individuals as well as patients with hepatitis B virus (HBV), liver cirrhosis
      (LC) and hepatocellular carcinoma (HCC) were purified, digested and subjected to
      liquid chromatography-electrospray ionization-higher energy collision
      dissociation mass spectrometry, which allowed identification and structure
      determination of the glycopeptide, as well as the relative quantification of
      glycans present on each glycopeptide. The quantitative results revealed that the
      sialylation of NLFLN(207)HSEN(211)ATAK and the fucosylated structure at all
      glycopeptides increased significantly in LC and HCC patients compared with those
      in HBV patients and healthy individuals. A set of different N-glycan patterns of
      Hp beta chain in various liver diseases has been determined. Thus, the sialylated
      and fucosylated glycoforms of Hp beta chain might be related to early
      hepatocarcinogenesis and also might be useful as novel differential markers for
      LC and HCC patients. 

PMID- 24103370
TI  - Nucleotide signaling in astrogliosis.
AB  - Acute and chronic damage to the central nervous system (CNS) releases large
      quantities of ATP. Whereas the ATP concentration in the extracellular space is
      normally in the micromolar range, under these conditions it increases to
      millimolar levels. A number of ligand-gated cationic channels termed P2X
      receptors (7 mammalian subtypes), and G protein-coupled P2Y receptors (8
      mammalian subtypes) are located at astrocytes, as confirmed by the measurement of
      the respective mRNA and protein. Activation of both the P2X7 and P2Y1,2 subtypes
      identified at astrocytes initiates astrogliosis isolating damaged brain areas
      from surrounding healthy cells and synthesizing neurotrophins and pleotrophins
      that participate in neuronal recovery. Astrocytes are considered as cells of high
      plasticity which may alter their properties in a culture medium. Therefore,
      recent work concentrates on investigating nucleotide effects at in situ (acute
      brain slices) and in vivo astrocytes. A wealth of data relates to the involvement
      of purinergic mechanisms in astrogliosis induced by acute CNS injury such as
      mechanical trauma and hypoxia/ischemia. The released ATP may act within minutes
      as an excitotoxic molecule; at a longer time-scale within days it causes
      neuroinflammation. These effects sum up as necrosis/apoptosis on the one hand and
      proliferation on the other. Although the role of nucleotides in chronic
      neurodegenerative illnesses is not quite clear, it appears that they aggravate
      the consequences of the primary disease. Epilepsy and neuropathic pain are also
      associated with the release of ATP and a pathologic glia-neuron interaction
      leading to astrogliosis and cell death. In view of these considerations, P2
      receptor antagonists may open new therapeutic vistas in all forms of acute and
      chronic CNS damage. 

PMID- 24103371
TI  - No Colavita effect: increasing temporal load maintains equal auditory and visual
      processing in people with one eye.
AB  - We investigate whether the loss of one eye leads to enhanced multisensory
      processing. Previously, we measured discrimination of auditory, visual and
      audiovisual targets in people with one eye compared to controls viewing
      binocularly or with one eye patched. Both control groups demonstrated typical
      visual dominance (the Colavita effect) whereas people with one eye show no
      Colavita effect, and instead show equal preference for visual and auditory
      stimuli. Here, we loaded temporal processing in an attempt to favour audition and
      thereby reverse Colavita visual dominance with a modified repetition blindness
      paradigm. The Colavita effect was reduced for controls however, people with one
      eye continued to show no Colavita effect, reversed or otherwise. People with one
      eye display equal auditory and visual processing in this context, suggesting
      unbiased multisensory processing, likely as a form of cross-modal adaptation and
      compensation for their loss of binocularity. 

PMID- 24103372
TI  - Interleukin-1 alpha (rs1800587) genetic polymorphism is associated with specific
      cognitive functions but not depression or loneliness in elderly males without
      dementia.
AB  - Inflammatory process is considered to be a pathway that results in
      neurodegeneration, and numerous plasma cytokines have been examined for their
      association with cognitive function and depression. Interleukin-1 alpha (IL-1A)
      genetic polymorphism (rs1800587) has been found to be associated with Alzheimer's
      disease susceptibility. The aim of this study was to investigate the effect of IL
      1A rs1800587 genetic effects on cognitive functions, loneliness and depression
      severity in elderly males without dementia or major depression. 192 non-demented
      Chinese elderly male were recruited and underwent Cognitive Abilities Screening
      Instrument (CASI), Wechsler Digit Span Task, Geriatric Depression Scale-short
      form, and UCLA Loneliness Scale assessment. IL-1A rs1800587 is a C to T
      transition at position -889. Compared to the C/C carriers, the T allele carriers
      had significantly overall higher CASI score (p=0.017) after using age and total
      education years as co-variates. This was especially true in the four distinct
      domains of long-term memory (p<0.001), orientation (p=0.017), visual construction
      (p=0.003), and list-generating fluency (p=0.020). This polymorphism is not
      associated with Geriatric Depression Scale-short form or UCLA Loneliness Scale.
      Our data supports that the T allele of IL-1A rs1800587 genetic polymorphism is
      associated with better cognitive function in the elderly. Further research will
      be needed to better understand the molecular mechanism for IL-1A genetic effects
      on cognitive function in the elderly. 

PMID- 24103373
TI  - Juvenile play experience primes neurons in the medial prefrontal cortex to be
      more responsive to later experiences.
AB  - Juvenile play behavior in rats promotes later behavioral flexibility and appears
      to do so by modifying the neural systems that regulate the animal's response to
      unexpected challenges. For example, the experience of play has been shown to
      prune the dendritic arbor of the cells in the medial prefrontal cortex (mPFC),
      part of the brain's executive control system. The objective of the present study
      was to determine if the play-induced changes in the mPFC promotes greater
      plasticity to experiences later in life. In order to test this possibility,
      exposure to nicotine was used as the secondary experience given later in life, as
      it has been shown to produce later changes to the morphology of mPFC pyramidal
      neurons. Animals were either paired with three same-sex peers (play condition) or
      one adult (no play condition) during their juvenile period. As young adults, half
      of the rats from each condition were exposed to repeated injections of nicotine
      and the other half to injections of saline. The neural plasticity of the mPFC was
      measured by changes in length and branching of dendrites. Neural changes induced
      separately by play and by nicotine were consistent with previously published
      findings. The novel finding was that the cells in the mPFC exhibit a greater
      response to exposure to nicotine if the rats first had play experience. These
      findings suggest that juvenile play experiences enhance the plasticity of some
      neural systems. 

PMID- 24103374
TI  - Self-assembling nanofibers improve cognitive impairment in a transgenic mice
      model of Alzheimer's disease.
AB  - The peptide amphiphile (PA) with a laminin epitope IKVAV (IKVAV-PA) can be
      trigged into three-dimensional nanostructures in vivo. Application of IKVAV-PA to
      the injured spinal cord resulted in significant functional improvement in rodents
      with remarkable axonal regeneration at the lesion site. Here we showed that
      injection of IKVAV-PA into the hippocampus of a transgenic (Tg) mice model of
      Alzheimer's disease (AD) significantly improved cognitive impairment, accompanied
      by an enhanced neurogenesis in the hippocampus. Further examination demonstrated
      that IKVAV-PA injections also significantly reduced the levels of soluble Abeta1
      40, Abeta1-42, and amyloid-beta (Abeta) plaques in these brains. Our data suggest
      that IKVAV-PA may serve as a potential therapeutic intervention for the learning
      and memory losses in AD. 

PMID- 24103375
TI  - ERP evidence for human early visual sensitivity to co-linearity compared to co
      circularity.
AB  - Our complex visual environment is constrained by natural geometric regularities,
      including spatiotemporal regularity, co-linearity and co-circularity. To
      investigate human visual processing associated with these regularities we
      directly compared the neural processes in encoding dynamic co-linearity and co
      circularity using event-related potentials (ERPs). By recording ERPs to a target
      bar presented alone (no context) or in a dynamic sequence of bars following a co
      linear or co-circular path, we observed earlier ERPs to targets embedded in co
      linear sequence at early (66ms) and later stages (197ms) of post-target
      processing. In contrast, targets in co-circular sequence only modulated ERPs at
      later stages of processing. It is proposed that early visual processing may have
      adapted to efficiently process co-linearity to improve target identification,
      whereas sensitivity to co-circularity does not occur until later stages of
      processing. These results have significant impact for understanding brain
      behaviour relationships when processing natural geometric regularities. 

PMID- 24103376
TI  - Gender versus brain size effects on subcortical gray matter volumes in the human
      brain.
AB  - Previous studies had reported that volume differences of gray matter (GM) in
      subcortical regions of the human brain were mainly caused by gender. Meanwhile,
      other studies had found that the distribution of GM in the human brain varied
      based on individual brain sizes. Main effects of volume differences of GM in
      subcortical regions remain unclear. Therefore, the goals of this study are
      twofold, namely, to determine the main effects of volume differences of GM in
      subcortical regions of the human brain and to investigate the independent or
      joint contribution of gender and brain size to subcortical volume differences. In
      this study, 40 male and 40 female subjects with comparable brain sizes were
      selected from a population of 198 individuals. The sample was divided into the
      following four groups: male and female groups with comparably large brain sizes
      and male and female groups with comparably small brain sizes. The main effects of
      gender and of brain size and interactions between both factors in subcortical GM
      volumes were examined by analyses of covariance (ANCOVAs) using a 2*2 design
      matrix. Volumes of GM in subcortical regions were extracted and measured by an
      automatic segmentation method. Furthermore, we used two datasets to test the
      reliability of our methods. In both datasets, we found significant brain size
      effects in the right amygdala and the bilateral caudate nucleus and significant
      gender effects in the bilateral putamen. No interactions between brain size and
      gender were found. In conclusion, both gender and brain size independently
      contributed to volume distribution in different subcortical areas of the human
      brain. 

PMID- 24103377
TI  - Involvement of dopaminergic receptors of the rat nucleus accumbens in decreasing
      the conditioned place preference induced by lateral hypothalamus stimulation.
AB  - Our previous study showed that chemical stimulation of the lateral hypothalamus
      (LH) by carbachol can produce conditioned place preference (CPP) in rats. Also,
      it has been indicated that orexin activates the mesolimbic dopamine projecting
      neurons to the nucleus accumbens (NAc) and promotes the development of reward in
      rodents. Therefore, in this study, we tried to determine the role of intra
      accumbal D1 and D2 dopamine receptors in the development (acquisition) of reward
      related behaviors induced by chemical stimulation of the LH. Eighty-eight adult
      male Wistar rats were unilaterally implanted by two separate cannulae into the LH
      and NAc. For chemical stimulation of LH, carbachol (250nmol/0.5MUl saline) was
      microinjected once daily during 3-days conditioning phase (acquisition period) of
      CPP paradigm. In the next experiments, different doses of D1 receptor antagonist,
      SCH23390 (0.25, 1 and 4MUg/0.5MUl saline) or sulpiride (0.25, 1 and 4MUg/0.5MUl
      DMSO) as a D2 receptor antagonist were unilaterally microinjected into the NAc,
      5min prior to LH stimulation. One-way ANOVA showed that intra-accumbal
      administration of SCH23390 or sulpiride can decrease the development of LH
      stimulation-induced CPP in the rats. However, this decrease is more effective
      after blockade of the D2 dopamine receptor in the NAc. It seems that the
      dopaminergic system in this area is involved in place preference induced by LH
      stimulation. 

PMID- 24103378
TI  - Suggesting a possible role of CA1 histaminergic system in harmane-induced
      amnesia.
AB  - A number of tremorogenic beta-carboline alkaloids such as harmane are naturally
      present in the human food chain. They are derived from medicinal plants such as
      Peganum harmala that have been used as folk medicine in anticancer therapy. In
      the present study, effects of the histaminergic system of the dorsal hippocampus
      (CA1) on harmane-induced amnesia were examined. One-trial step-down was used to
      assess memory retention in adult male mice. The results showed that pre-training
      intra-CA1 administration of histamine (5MUg/mouse), ranitidine (H2 receptor
      antagonist; at the doses of 0.25 and 0.5MUg/mouse) and pyrilamine (H1 receptor
      antagonist; at the dose of 5MUg/mouse) decreased memory formation. Pre-training
      intraperitoneal (i.p.) administration of harmane (12mg/kg) also decreased memory
      formation. Moreover, pre-training intra-CA1 injection of a sub-threshold dose of
      histamine (2.5MUg/mouse) could reverse harmane (12mg/kg, i.p.)-induced impairment
      of memory. On the other hand, pre-training intra-CA1 injection of sub-threshold
      doses of ranitidine (0.0625MUg/mouse) and pyrilamine (2.5MUg/mouse) increased
      harmane-induced impairment of memory. In conclusion, the present findings suggest
      the involvement of the CA1 histaminergic system in harmane-induced impairment of
      memory formation. 

PMID- 24103380
TI  - Dietary intake of n-3 long-chain polyunsaturated fatty acids and risk of
      myocardial infarction in coronary artery disease patients with or without
      diabetes mellitus: a prospective cohort study.
AB  - BACKGROUND: A beneficial effect of a high n-3 long-chain polyunsaturated fatty
      acid (LCPUFA) intake has been observed in heart failure patients, who are
      frequently insulin resistant. We investigated the potential influence of impaired
      glucose metabolism on the relation between dietary intake of n-3 LCPUFAs and risk
      of acute myocardial infarction (AMI) in patients with coronary artery disease.
      METHODS: This prospective cohort study was based on the Western Norway B-Vitamin
      Intervention Trial and included 2,378 patients with coronary artery disease with
      available baseline glycosylated hemoglobin (HbA1c) and dietary data. Patients
      were sub-grouped as having no diabetes (HbA1c <5.7%), pre-diabetes (HbA1c
      >=5.7%), or diabetes (previous diabetes, fasting baseline serum glucose >=7.0, or
      non-fasting glucose >=11.1 mmol/L). AMI risk was evaluated by Cox regression (age
      and sex adjusted), comparing the upper versus lower tertile of daily dietary n-3
      LCPUFA intake. RESULTS: The participants (80% males) had a mean age of 62 and
      follow-up of 4.8 years. A high n-3 LCPUFA intake was associated with reduced risk
      of AMI (hazard ratio 0.38, 95%CI 0.18, 0.80) in diabetes patients (median HbA1c =
      7.2%), whereas no association was observed in pre-diabetes patients. In patients
      without diabetes a high intake tended to be associated with an increased risk
      (hazard ratio1.45, 95%CI 0.84, 2.53), which was significant for fatal AMI (hazard
      ratio 4.79, 95%CI 1.05, 21.90) and associated with lower HbA1c (mean +/- standard
      deviation 4.55 +/-0.68 versus 4.92 +/-0.60, P = 0.02). No such differences in
      HbA1c were observed in those with pre-diabetes or diabetes. CONCLUSIONS: A high
      intake of n-3 LCPUFAs was associated with a reduced risk of AMI, independent of
      HbA1c, in diabetic patients, but with an increased risk of fatal AMI and lower
      HbA1c among patients without impaired glucose metabolism. Further studies should
      investigate whether patients with diabetes may benefit from having a high intake
      of n-3 LCPUFAs and whether patients with normal glucose tolerance should be
      careful with a very high intake of these fatty acids. TRIAL REGISTRATION: This
      trial is registered at clinicaltrials.gov as NCT00354081.

PMID- 24103379
TI  - Psychosis in Alzheimer's disease.
AB  - Psychotic symptoms, delusions and hallucinations, occur in approximately 50% of
      individuals with Alzheimer's disease (AD) (AD with psychosis [AD + P]).
      Pharmacotherapies for AD + P have limited efficacy and can increase short-term
      mortality. These observations have motivated efforts to identify the underlying
      biology of AD + P. Psychosis in AD indicates a more severe phenotype, with more
      rapid cognitive decline beginning even before psychosis onset. Neuroimaging
      studies suggest that AD + P subjects demonstrate greater cortical synaptic
      impairments than AD subjects without psychosis, reflected in reduced gray matter
      volume, reduced regional blood flow, and reduced regional glucose metabolism.
      Neuroimaging and available postmortem evidence further indicate that the
      impairments in AD + P, relative to AD subjects without psychosis, are localized
      to neocortex rather than medial temporal lobe. Neuropathologic studies provide
      consistent evidence of accelerated accumulation of hyperphosphorylated
      microtubule associated protein tau in AD + P. Finally, studies of familial
      aggregation of AD + P have established that the risk for psychosis in AD is, in
      part, genetically mediated. Although no genes are established as associated with
      AD + P, the first genome-wide association study of AD + P has generated some
      promising leads. The study of the neurobiology of AD + P is rapidly accelerating
      and may be poised for translational discovery. This process can be enhanced by
      identifying points of convergence and divergence with the neurobiology of AD
      proper and of schizophrenia, by innovative extension of current approaches, and
      by development of relevant animal models. 

PMID- 24103381
TI  - Physical activity and the rejuvenation of Connswater (PARC study): protocol for a
      natural experiment investigating the impact of urban regeneration on public
      health.
AB  - BACKGROUND: There is a dearth of evidence regarding the impact of urban
      regeneration projects on public health, particularly the nature and degree to
      which urban regeneration impacts upon health-related behaviour change. Natural
      experiment methodology enables comprehensive large-scale evaluations of such
      interventions. The Connswater Community Greenway in Belfast is a major urban
      regeneration project involving the development of a 9 km linear park, including
      the provision of new cycle paths and walkways. In addition to the environmental
      improvements, this complex intervention involves a number of programmes to
      promote physical activity in the regenerated area. The project affords a unique
      opportunity to investigate the public health impact of urban regeneration.
      METHODS/DESIGN: The evaluation framework was informed by the socio-ecological
      model and guided by the RE-AIM Framework. Key components include: (1) a quasi
      experimental before-and-after survey of the Greenway population (repeated cross
      sectional design), in tandem with data from a parallel Northern Ireland-wide
      survey for comparison; (2) an assessment of changes in the local built
      environment and of walkability using geographic information systems; (3) semi
      structured interviews with a purposive sample of survey respondents, and a range
      of community stakeholders, before and after the regeneration project; and (4) a
      cost-effectiveness analysis. The primary outcome is change in proportion of
      individuals identified as being regularly physically active, according to the
      current UK recommendations. The RE-AIM Framework will be used to make an overall
      assessment of the impact of the Greenway on the physical activity behaviour of
      local residents. DISCUSSION: The Connswater Community Greenway provides a
      significant opportunity to achieve long-term, population level behaviour change.
      We argue that urban regeneration may be conceptualised meaningfully as a complex
      intervention comprising multiple components with the potential, individually and
      interactively, to affect the behaviour of a diverse population. The development
      and implementation of our comprehensive evaluation framework reflects this
      complexity and illuminates an approach to the empirical, rigorous evaluation of
      urban regeneration. More specifically, this study will add to the much needed
      evidence-base about the impact of urban regeneration on public health as well as
      having important implications for the development of natural experiment
      methodology.

PMID- 24103382
TI  - Incidence of acute respiratory infections in Australia.
AB  - We used a national survey of 7578 randomly selected respondents in 2008-2009 to
      identify the period prevalence of acute respiratory infection (ARI) by season and
      state, and to estimate the incidence of ARI in the Australian community. A case
      was defined as any episode of cold or flu with at least one of the following
      symptoms: fever, chills, sore throat, running nose, or cough in the past 4 weeks.
      Frequency data were weighted to the Australian population. The response rate to
      the survey was 49%, and 19.9% (1505/7578) of respondents reported an ARI in the
      previous 4 weeks, which extrapolated to 68.9 million cases [95% confidence
      interval (CI) 65.1-72.7] of ARI in Australia annually. The incidence was 3.2 (95%
      CI 3.0-3.4) cases of ARI/person per year, and was highest in young children and
      lowest in older people. ARI imposes a significant burden on Australian society.

PMID- 24103383
TI  - Removing QoF targets will take funding away from general practice, says Gerada.

PMID- 24103385
TI  - Cholesterol: fa(s)t-food for enterovirus genome replication.
AB  - Hijacking and remodeling of host membranes is an obligatory step in the
      replicative cycle of (+)RNA viruses, including enteroviruses. Ilnytska et al.
      unveiled in Cell Host & Microbe that enteroviruses usurp clathrin-mediated
      endocytosis to shuttle cholesterol to sites of genome replication and that
      cholesterol is needed for efficient replication. 

PMID- 24103384
TI  - Effects and costs of home-based training with telemonitoring guidance in low to
      moderate risk patients entering cardiac rehabilitation: The FIT@Home study.
AB  - BACKGROUND: Physical training has beneficial effects on exercise capacity,
      quality of life and mortality in patients after a cardiac event or intervention
      and is therefore a core component of cardiac rehabilitation. However, cardiac
      rehabilitation uptake is low and effects tend to decrease after the initial
      rehabilitation period. Home-based training has the potential to increase cardiac
      rehabilitation uptake, and was shown to be safe and effective in improving short
      term exercise capacity. Long-term effects on physical fitness and activity,
      however, are disappointing. Therefore, we propose a novel strategy using
      telemonitoring guidance based on objective training data acquired during exercise
      at home. In this way, we aim to improve self-management skills like self-efficacy
      and action planning for independent exercise and, consequently, improve long-term
      effectiveness with respect to physical fitness and physical activity. In
      addition, we aim to compare costs of this strategy with centre-based cardiac
      rehabilitation. METHODS/DESIGN: This randomized controlled trial compares a 12
      week telemonitoring guided home-based training program with a regular, 12-week
      centre-based training program of equal duration and training intensity in low to
      moderate risk patients entering cardiac rehabilitation after an acute coronary
      syndrome or cardiac intervention. The home-based group receives three supervised
      training sessions before they commence training with a heart rate monitor in
      their home environment. Participants are instructed to train at 70-85% of their
      maximal heart rate for 45-60 minutes, twice a week. Patients receive individual
      coaching by telephone once a week, based on measured heart rate data that are
      shared through the internet. Primary endpoints are physical fitness and physical
      activity, assessed at baseline, after 12 weeks and after one year. Physical
      fitness is expressed as peak oxygen uptake, assessed by symptom limited exercise
      testing with gas exchange analysis; physical activity is expressed as physical
      activity energy expenditure, assessed by tri-axial accelerometry and heart rate
      measurements. Secondary endpoints are training adherence, quality of life,
      patient satisfaction and cost-effectiveness. DISCUSSION: This study will increase
      insight in long-term effectiveness and costs of home-based cardiac rehabilitation
      with telemonitoring guidance. This strategy is in line with the trend to shift
      non-complex healthcare services towards patients' home environments. TRIAL
      REGISTRATION: Dutch Trial Register: NTR3780. Clinicaltrials.gov register:
      NCT01732419.

PMID- 24103386
TI  - Development, validation and high-throughput analysis of sequence markers in
      nonmodel species.
AB  - DNA sequences derived from multiple regions of the nuclear genome are essential
      for historical inferences in the fields of phylogeography and phylogenetics. The
      appropriate markers should be single-copy, variable, easy to amplify from
      multiple samples and easy to sequence using high-throughput technologies. This
      may be difficult to achieve for species lacking sequenced genomes and
      particularly challenging for species possessing large genomes, which consist
      mostly of repetitive sequences. Here, we present a cost-effective, broadly
      applicable framework for designing, validating and high-throughput sequencing of
      multiple markers in nonmodel species without sequenced genomes. We demonstrate
      its utility in two closely related species of newts, representatives of urodeles,
      a vertebrate group characterized by large genomes. We show that over 80 markers,
      c. 600 bp each, developed mainly from 3' untranslated transcript regions (3'UTR)
      may be effectively multiplexed and sequenced. Data are further processed using
      standard, freely available bioinformatic tools, producing phase-resolved
      sequences. The approach does not require barcoded PCR primers, and the cost of
      library preparation is independent of the number of markers investigated. We hope
      that this approach will be of broad interest for researchers working at the
      interface of population genetics and phylogenetics, exploring deep intraspecific
      genetic structure, species boundaries and phylogeographies of closely related
      species.

PMID- 24103388
TI  - Development of a competency framework for the nutrition in emergencies sector.
AB  - OBJECTIVE: There is a recognised need to strengthen capacity in the nutrition in
      emergencies sector and for greater clarity on the role of emergency nutritionists
      and the skills they require. Competency frameworks are an important tool for
      human resource development and have been developed for several other humanitarian
      sectors. We therefore developed a technical competency framework for
      practitioners in nutrition in emergencies. DESIGN: Existing competency frameworks
      were reviewed and interviews conducted to explore methods used in developing
      competency frameworks for other sectors. Competencies were identified through
      interviews with field experts, feedback from course trainees, academic course
      content and job specifications. Competencies were then categorised and
      behavioural indicators developed for each. The draft framework was then reviewed
      by members of the Global Nutrition Cluster and modified in an iterative process.
      SETTING: Global. SUBJECTS: Not applicable. RESULTS: A wide range of competencies
      were identified as essential for nutritionists working in emergencies, covering
      technical skills and general core competencies. The proposed framework contains
      twenty competency areas with 161 behavioural indicators categorised into three
      levels, corresponding to the requirements of progressively more senior roles.
      Many of the competencies are common across development and emergency nutrition.
      CONCLUSIONS: The proposed technical competency framework should prove to be a
      valuable tool in creating standards within the sector and promoting effective
      capacity strengthening and professionalisation. Continued research is needed to
      validate the framework, optimise methods for assessment, develop approaches to
      integrate it within the sector and measure its impact on performance.

PMID- 24103387
TI  - The role of APP and BACE1 trafficking in APP processing and amyloid-beta
      generation.
AB  - Neuritic plaques in the brain are a major neuropathological hallmark of
      Alzheimer's disease. They are formed by the deposition and aggregation of
      extracellular amyloid-beta protein (Abeta). Abeta is derived from the sequential
      cleavage of amyloid-beta precursor protein (APP) by beta-secretase and gamma
      secretase. beta-Site APP cleaving enzyme 1 (BACE1) functions as the primary, if
      not sole, beta-secretase in vivo and is essential for Abeta production.
      Regulation of APP processing is a major focus of research into AD pathogenesis.
      The trafficking systems of APP and its cleavage enzymes are complex. Transporting
      APP and secretases into the same subcellular organelles facilitates their
      interaction and favors APP processing. The role of APP and BACE1 trafficking in
      the amyloidgenic pathway and the underlying mechanisms for Abeta production are
      discussed in this review. In addition, the distinct mechanisms of amino- and
      carboxy-terminal Abeta generation are reviewed. 

PMID- 24103389
TI  - Head and neck squamous cell carcinoma in young patients.
AB  - Epidemiologic analyses have shown disproportional increases of head and neck
      squamous cell carcinoma (HNSCC) incidence in a younger age group (younger than 45
      years old), compared to patients above 45 years old. Although this group is small
      (5%), it includes a significant subset of the HNSCC patient population, and is
      characterized by a distinct clinical and etiological phenotype. HNSCC in young
      patients often presents without significant exposure to alcohol and tobacco and
      primarily affects the oropharynx and oral cavity. Exposure to human papilloma
      virus (HPV) has been identified as a major contributor to the pathogenesis of
      oropharyngeal carcinomas, and explains part of the observed incidence variation.
      Specific hereditary influences, including genetic predispositions accounting for
      an increased mutagen sensibility and inherited syndromes like Fanconi Anemia and
      Bloom's syndrome, have been identified as causative factors in a subgroup of
      young-onset HNSCC, but their cumulative influence remains at present likely
      underestimated. Circumstantial evidence suggests that young-onset HNSCC patients
      have a clinically different phenotype compared to older patients, however, the
      true impact of young age on HNSCC clinical behavior will remain difficult to
      determine unless multi-institutional databases will be combined. The rising
      incidence of young-onset HNSCC mandates intensification of research endeavors
      into its etiology, clinical phenotype and optimal management.

PMID- 24103390
TI  - Acute depletion of endothelial beta3-integrin transiently inhibits tumor growth
      and angiogenesis in mice.
AB  - RATIONALE: The dramatic upregulation of alphavbeta3-integrin that occurs in the
      vasculature during tumor growth has long suggested that the endothelial
      expression of this molecule is an ideal target for antiangiogenic therapy to
      treat cancer. This discovery led to the development of small-molecule inhibitors
      directed against alphavbeta3-integrin that are currently in clinical trials. In
      2002, we reported that beta3-integrin-knockout mice exhibit enhanced tumor growth
      and angiogenesis. However, as beta3-integrin is expressed by a wide variety of
      cells, endothelial cell-specific contributions to tumor angiogenesis are muddied
      by the use of a global knockout of beta3-integrin function. OBJECTIVE: Our aim
      was to examine the endothelial-specific contribution beta3-integrin makes to
      tumor growth and angiogenesis. METHODS AND RESULTS: We have crossed beta3
      integrin-floxed (beta3-floxed) mice to 2 endothelial-specific Cre models and
      examined angiogenic responses in vivo, ex vivo, and in vitro. We show that acute
      depletion of endothelial beta3-integrin inhibits tumor growth and angiogenesis
      preventatively, but not in already established tumors. However, the effects are
      transient, and long-term depletion of the molecule is ineffective. Furthermore,
      long-term depletion of the molecule correlates with many molecular changes, such
      as reduced levels of focal adhesion kinase expression and a misbalance in focal
      adhesion kinase phosphorylation, which may lead to a release from the inhibitory
      effects of decreased endothelial beta3-integrin expression. CONCLUSIONS: Our
      findings imply that timing and length of inhibition are critical factors that
      need to be considered when targeting the endothelial expression of beta3-integrin
      to inhibit tumor growth and angiogenesis.

PMID- 24103391
TI  - GABAergic excitation of vasopressin neurons: possible mechanism underlying sodium
      dependent hypertension.
AB  - RATIONALE: Increased arginine-vasopressin (AVP) secretion is a key physiological
      response to hyperosmotic stress and may be part of the mechanism by which high
      salt diets induce or exacerbate hypertension. OBJECTIVE: Using
      deoxycorticosterone acetate-salt hypertension model rats, we sought to test the
      hypothesis that changes in GABA(A) receptor-mediated inhibition in AVP-secreting
      magnocellular neurons contribute to the generation of Na(+)-dependent
      hypertension. METHODS AND RESULTS: In vitro gramicidin-perforated recordings in
      the paraventricular and supraoptic nuclei revealed that the GABAergic inhibition
      in AVP-secreting neurons was converted into excitation in this model, because of
      the depolarization of GABA equilibrium potential. Meanwhile, in vivo
      extracellular recordings in the supraoptic nuclei showed that the GABAergic
      baroreflexive inhibition of magnocellular neurons was transformed to excitation,
      so that baroreceptor activation may increase AVP release. The depolarizing GABA
      equilibrium potential shift in AVP-secreting neurons occurred progressively over
      weeks of deoxycorticosterone acetate-salt treatment along with gradual increases
      in plasma AVP and blood pressure. Furthermore, the shift was associated with
      changes in chloride transporter expression and partially reversed by bumetanide
      (Na(+)-K(+)-2Cl(-) cotransporter inhibitor). Intracerebroventricular bumetanide
      administration during deoxycorticosterone acetate-salt treatment hindered the
      development of hypertension and rise in plasma AVP level. Muscimol (GABA(A)
      agonist) microinjection into the supraoptic nuclei in hypertensive rats increased
      blood pressure, which was prevented by previous intravenous V1a AVP antagonist
      injection. CONCLUSIONS: We conclude that the inhibitory-to-excitatory switch of
      GABAA receptor-mediated transmission in AVP neurons contributes to the generation
      of Na(+)-dependent hypertension by increasing AVP release. We speculate that
      normalizing the GABA equilibrium potential may have some utility in treating
      Na(+)-dependent hypertension.

PMID- 24103392
TI  - Balance artistry: the healthy parent's role in the family when the other parent
      is in the palliative phase of cancer--challenges and coping in parenting young
      children.
AB  - OBJECTIVES: The aim of this review was to provide a systematic overview of
      knowledge on how advanced cancer in a parent impacts the healthy parent's role in
      a family with children aged 6-12 years, and the types of help that they require
      in order to cope. Despite the large number of families living with a parent
      affected by cancer, the literature is limited concerning the needs and outcomes
      for the healthy parents and their need for support in managing their children's
      needs, when the partner is seriously ill or is in the palliative phase of cancer.
      METHOD: Comprehensive literature searches were undertaken by systematically
      searching for qualitative articles published during the period 1989-2009. The
      quality assessment was evaluated using a predefined "checklist to assess
      qualitative research." RESULTS: Seven articles met our eligibility criteria. Four
      distinct themes emerged that describe the healthy parent's role in the family,
      whose life is now characterized by uncertainty and who is attempting to maintain
      a balance between the needs of their children, the patient, and themselves: (1)
      new roles without a script, (2) attempting to maintain a safe and normal life,
      (3) feeling alone even within the family, and (4) support to help young family
      members. SIGNIFICANCE OF RESULTS: The present review provides new knowledge and
      insight into how healthy parents manage the challenges in parenting young
      children, coping with their everyday lives, and taking on new roles when their
      partner has advanced cancer or is dying. The healthy parent cannot balance the
      needs of all family members. To reach the goals of palliative care, nurses and
      other health professionals are encouraged to offer the patient, the healthy
      parent, and the children practical and emotional support.

PMID- 24103393
TI  - Identification of water pathogens by Raman microspectroscopy.
AB  - Legionella species can be found living in water mostly in a viable but
      nonculturable state or associated with protozoa and complex biofilm formations.
      Isolation and afterwards identification of these pathogens from environmental
      samples by using common identification procedures based on cultivation are
      extremely difficult and prolonged. The development of fast and sensitive method
      based on the cultivation free identification of bacteria is necessary. In this
      study Raman microspectroscopy combined with multiclass support vector machines
      have been used to discriminate between Legionella and other common aquatic
      bacteria, to distinguish among clinically relevant Legionella species and to
      classify unknown Raman spectra for a fast and reliable identification. Recorded
      Raman spectra of the twenty-two Legionella species as well as the Raman spectra
      of Escherichia coli, Klebsiella pneumoniae and Pseudomonas aeruginosa were
      utilized to build the classification model. Afterwards, independent Raman spectra
      of eleven species were used to identify them on the basis of the classification
      model that was created. The present study shows that Raman microspectroscopy can
      be used as a rapid and reliable method to distinguish between Legionella species
      recognized as human pathogens and to identify samples which are unknown to the
      model based on multiclass support vector machines (MC-SVM). 

PMID- 24103394
TI  - Comparison of two different anaerobic feeding strategies to establish a stable
      aerobic granulated sludge bed.
AB  - Two different anaerobic feeding strategies were compared to optimize the
      development and performance of aerobic granules. A stable aerobic granulation of
      activated sludge was achieved with an anaerobic plug flow operation (PI) and a
      fast influent step followed by an anaerobic mixing phase (PII). Two lab scale
      sequencing batch reactors (SBRs) were operated to test the different operation
      modes. PI with plug flow and a reactor H/D (height/diameter) ratio of 9 achieved
      a biomass concentration of 20 g(TSS)/L and an effluent TSS concentration of 0.10
      g(TSS)/L. PII with the mixed anaerobic phase directly after feeding and a reactor
      H/D ratio of 2 achieved a biomass concentration of 9 g(TSS)/L and an effluent
      quality of 0.05 g(TSS)/L. Furthermore, it is shown that the plug flow regime
      during anaerobic feeding together with the lower H/D ratio of 2 led to channeling
      effects, which resulted in lower storage of organic carbon and a general
      destabilization of the granulation process. Compared to the plug flow regime
      (PI), the anaerobic mixing (PII) provided lower substrate gradients within the
      biofilm. However, these disadvantages could be compensated by higher mass
      transfer coefficients in PII (k(L) = 0.3 m/d for PI; k(L) = 86 m/d for PII)
      during the anaerobic phase.

PMID- 24103395
TI  - Sex differences in the composition of weight gain and loss in overweight and
      obese adults.
AB  - Sex differences in the ratio of fat mass (FM):fat-free mass (FFM) during weight
      change should differentially affect the extent of weight change during energy
      imbalance in men and women. In the present study, we determined FM and FFM
      contents by dual-energy X-ray absorptiometry and calculated the P-ratios (protein
      energy/total energy) of excess weight and weight loss during a randomised
      controlled trial of four commercial weight loss regimens. Overweight and obese
      women (n 210) and men (n 77) were studied at baseline and at 2 and 6 months
      during weight loss on four dietary regimens: Dr Atkins' New Diet Revolution; The
      Slim-Fast Plan; Weight-Watchers programme; Rosemary Conley's Diet and Fitness
      Plan. At baseline, the percentage of FFM (%FFM) and P-ratios of excess weight
      were 40 % and 0.071 for men and 27 % and 0.039 for women. At 2 months, men had
      lost twice as much weight as women and three times more FFM than women,
      indicating higher FFM content and P-ratios of weight loss for men, 0.052, than
      for women, 0.029, with no dietary effects. Between 2 and 6 months, the rate at
      which weight was lost decreased and the %FFM of weight loss decreased to similar
      low levels in men (7 %) and women (5 %): i.e. P-ratios of 0.009 and 0.006,
      respectively, with no dietary effects. Thus, for men compared with women, there
      were greater FFM content and P-ratios of weight change, which could partly, but
      not completely, explain their greater weight loss at 2 months. However, protein
      conserving adaptations occur with increasing weight loss and over time, more
      extensively in men, eventually eliminating any sex difference in the composition
      of weight loss.

PMID- 24103396
TI  - Partial penectomy and penile reconstruction. Initial surgical management of
      localized penile cancer.
AB  - INTRODUCTION: Surgical management for penile carcinoma is mutilating and affects
      significantly quality of life. Hereby we present our experience on penile
      reconstruction (PR) immediately after oncologic resection. MATERIALS AND METHODS:
      We included all patients from January 2007 until April 2012 who underwent PR
      after partial penectomy (PP). Patients included in the study were seen at four
      different hospitals. All procedures were done by the same surgeon. Information
      included were: oncological status at the moment of surgery, surgical technique
      used for reconstruction. Each case was also registered photographically. On
      follow-up visits data about outcome and patient's satisfaction were registered.
      RESULTS: During the study period 15 patients underwent PR. Average age at the
      moment of surgery was 49 years. Average follow-up was 15 months. In 12 patients
      PR was made at the same time as PP. Of those, four cases underwent glans
      resurfacing, 2 glandectomy, 6 partial penectomy, and the remaining 3 have had PP
      in a different time in the past. Every case underwent a split thickness graft
      procedure. Only 2 patients had postoperative complications. One of them presented
      urethral stricture and the other graft ischemia. Three patients had positive
      nodes at the moment of PP and two during the follow-up. None of the cases have
      presented local recurrence and only one died. On follow-up the remaining patients
      refer a good quality of life and felt happy with aesthetic results. CONCLUSIONS:
      Given the results presented hereby we propose that PR must be part of the same
      procedure as the PP.

PMID- 24103397
TI  - Antisense oligonucleotide suppression of human IGF-1R inhibits the growth and
      survival of in vitro cultured epithelial ovarian cancer cells.
AB  - BACKGROUND: Preclinical evaluation of the anti-neoplastic activity of antisense
      oligonucleotide (AS) suppression of human insulin-like growth factor I receptor
      (IGF-IR) in human epithelial ovarian cancer (EOC). METHODS: Ovarian cancer cells
      from 36 patients with EOC were investigated under serum-free tissue culture
      conditions. IGF-I production was evaluated by standard ELISA. IGF-IR and
      phosphorylated IRS-1, AKT, and MAP kinase expression and protein levels were
      evaluated by immunohistochemistry and Western blotting. Cancer cell growth and
      proliferation assays were performed in triplicates using MTT assay. Apoptosis was
      evaluated by TUNNEL assay. RESULTS: All ovarian cancer tissue samples tested
      produced IGF-I and expressed IGF-IR, supporting the existence of an autocrine
      loop. Treatment of primary ovarian cancer cell lines with an IGF-1R AS inhibited
      growth and proliferation and decreased clonogenicity in soft agar assay. AS
      treatment was demonstrated to inhibit the expression of IGF-1R and decrease the
      concentration of phosphorylated IRS-1, AKT, and MAP kinase signaling protein
      downstream of the IGF-IR. We also observed that the IGF-1R AS sensitized cancer
      cell lines to cisplatin in vitro through the PI3K pathway. CONCLUSIONS: IGF-IR
      enhances the proliferation and tumorigenicity of human ovarian cancer cells and
      inhibition of IGF-IR by AS oligonucleotide treatment potentiates the activity of
      cisplatin in vitro. Therefore, IGF-1R is a potential molecular target in ovarian
      cancer.

PMID- 24103398
TI  - Changes and tracking of fruit, vegetables and sugar-sweetened beverages intake
      from 18 months to 7 years in the Norwegian Mother and Child Cohort Study.
AB  - BACKGROUND: A few studies have investigated tracking of dietary patterns or
      nutrient intake in pre-school children, but no studies have been identified
      examining tracking of sugar-sweetened beverages (SSB), fruit and vegetable
      intakes in early childhood (1-7 year olds). The purpose of this study was to
      investigate changes and tracking of intakes of fruit, vegetables and SSB, and
      association between maternal education and dietary tracking, from 18 months to 7
      years of age. METHODS: Longitudinal data from the nation-wide Norwegian Mother
      and Child Cohort Study, conducted by the Norwegian Institute of Public Health
      were used, including 9025 children participating at three time points (18 months,
      36 months and 7 years). Frequencies of fruit, vegetables and SSB were assessed by
      questionnaire. Slightly different questions were used at each time point to
      collect information about intake. Maternal education was categorized into <= 12
      years, 13-16 years, >= 17 years. Cross-tabulation, Spearman's rho and multinomial
      logistic regression were used for assessing change, tracking and differences by
      maternal education. RESULTS: Analyses by gender indicated largest changes for
      intake of fruit and SSB from age 18 months to 7 years. Fair to moderate tracking
      coefficients (Spearman's rho = 0.23-0.46) for intake of fruit, vegetables and SSB
      were found and children assigned to low, medium and high frequency of consumption
      at 18 months continued to be in the same group at age 36 months and 7 years.
      Children of mothers with low education consumed fruit and vegetables less often
      and SSB more often compared to children of mothers with high education at 18
      months of age. Children with higher educated mothers had lower odds for
      increasing fruit intake or decreasing SSB intake, compared to children with lower
      educated mothers showing a stable intake. CONCLUSIONS: The tracking coefficients
      for intakes were fair to moderate and differences in intakes according to
      maternal education were found already at age 18 months. This suggests that
      promotion of healthy dietary behaviours at an early age is important to prevent
      unfavourable dietary behaviours later in childhood. Moreover, it seems important
      to target mothers in nutrition interventions for improving dietary habits among
      children.

PMID- 24103399
TI  - Schmallenberg virus detection in bovine semen after experimental infection of
      bulls.
AB  - To study Schmallenberg virus (SBV) excretion in bovine semen after experimental
      infection, two bulls were inoculated subcutaneously with a SBV isolate (1 ml Vero
      cell culture 106 TCID50). After inoculation (at day 0), semen was collected daily
      from both animals for 21 days and samples were tested for SBV by qRT-PCR assay.
      At 24 days post-inoculation both animals were subjected to necropsy and the
      genital organs and lymph nodes draining these organs were also tested for SBV RNA
      (qRT-PCR). After SBV infection both animals in the study showed viraemia (qRT
      PCR) with fever and diarrhoea. SBV RNA could be detected in semen from both
      animals. The highest SBV RNA concentrations in semen were found in the first week
      (days 4-7 post-inoculation) but concentrations were relatively low (Ct values 30
      39). Viable SBV was only isolated from blood samples and not from semen or
      genital tissues.

PMID- 24103400
TI  - Lifelong bilingualism contributes to cognitive reserve against white matter
      integrity declines in aging.
AB  - Recent evidence suggests that lifelong bilingualism may contribute to cognitive
      reserve (CR) in normal aging. However, there is currently no neuroimaging
      evidence to suggest that lifelong bilinguals can retain normal cognitive
      functioning in the face of age-related neurodegeneration. Here we explored this
      issue by comparing white matter (WM) integrity and gray matter (GM) volumetric
      patterns of older adult lifelong bilinguals (N=20) and monolinguals (N=20). The
      groups were matched on a range of relevant cognitive test scores and on the
      established CR variables of education, socioeconomic status and intelligence.
      Participants underwent high-resolution structural imaging for assessment of GM
      volume and diffusion tensor imaging (DTI) for assessment of WM integrity. Results
      indicated significantly lower microstructural integrity in the bilingual group in
      several WM tracts. In particular, compared to their monolingual peers, the
      bilingual group showed lower fractional anisotropy and/or higher radial
      diffusivity in the inferior longitudinal fasciculus/inferior fronto-occipital
      fasciculus bilaterally, the fornix, and multiple portions of the corpus callosum.
      There were no group differences in GM volume. Our results suggest that lifelong
      bilingualism contributes to CR against WM integrity declines in aging. 

PMID- 24103401
TI  - Temperamental precursors of infant attachment with mothers and fathers.
AB  - The degree to which parent sensitivity and infant temperament distinguish
      attachment classification was examined. Multilevel modeling was used to assess
      the effect of parent sensitivity and infant temperament on infant-mother and
      infant-father attachment. Data were collected from mothers, fathers, and their
      infants (N = 135) when the infant was 3-, 5-, 7-, 12-, and 14-months old.
      Temperament was measured using the Infant Behavior Questionnaire-Revised
      (Gartstein & Rothbart, 2003); parent sensitivity was coded during the Still Face
      Paradigm (Tronick, Als, Adamson, Wise, & Brazelton, 1978); attachment was coded
      using the Strange Situation (Ainsworth, Blehar, Waters, & Wall, 1978). Results
      indicate that mothers and fathers were less sensitive with insecure-avoidant
      infants. Whereas only one difference was found for infant-mother attachment
      groups and temperament, five significant differences emerged for infant-father
      attachment groups, with the majority involving insecure-ambivalent attachment.
      Infants classified as ambivalent with fathers were higher in perceptual
      sensitivity and cuddliness and these infants also showed a greater increase in
      low-intensity pleasure over time compared with other infants. Results indicate
      the importance of both parent sensitivity and infant temperament, though
      operating in somewhat different ways, in the development of the infant-mother and
      infant-father attachment relationship.

PMID- 24103402
TI  - Altered rate-dependent depression of the spinal H-reflex as an indicator of
      spinal disinhibition in models of neuropathic pain.
AB  - The unpredictable efficacy of current therapies for neuropathic pain may reflect
      diverse etiological mechanisms operating between, and within, diseases. As
      descriptions of pain rarely establish specific mechanisms, a tool that can
      identify underlying causes of neuropathic pain would be useful in developing
      patient-specific treatments. Rate-dependent depression (RDD), a measure of the
      change in amplitude of the Hoffman reflex over consecutive stimulations, is
      attenuated in diabetic rats that also exhibit impaired spinal gamma-aminobutyric
      acid (GABA)A receptor function, reduced spinal potassium chloride co-transporter
      (KCC2) expression, and indices of painful neuropathy. To investigate whether loss
      of RDD is a reliable indicator of the contribution of spinal GABAergic
      dysfunction to neuropathic pain, we assessed RDD, tactile allodynia, and formalin
      evoked hyperalgesia in 3 models: rats treated acutely with brain-derived
      neurotrophic factor (BDNF), diabetic rats treated with the BDNF-sequestering
      molecule tyrosine receptor kinase B/Fc (TrkB/Fc), and rats with paclitaxel
      induced neuropathy. Delivery of BDNF to the spinal cord of normal rats produced
      RDD deficits and features of painful neuropathy associated with disrupted GABAA
      receptor-mediated inhibitory function and reduced dorsal spinal KCC2 expression.
      Treating diabetic rats with TrkB/Fc restored RDD and alleviated indices of
      painful neuropathy. In paclitaxel-treated rats, RDD was not impaired and
      behavioral indices of neuropathic pain were not associated with spinal GABAergic
      dysfunction or reduced dorsal spinal KCC2 expression. Our data reveal BDNF as
      part of the mechanism underlying spinal cord disinhibition caused by altered
      GABAA receptor function in diabetic rats and suggest that RDD deficits may be a
      useful indicator of neuropathic pain states associated with spinal disinhibition,
      thereby revealing specific therapeutic targets. 

PMID- 24103403
TI  - Transjugular Balloon Pulmonary Valvuloplasty Through a Bidirectional Glenn Shunt
      for Dysplastic Pulmonary Valve Stenosis in an 8.7-Year-Old Boy with Inaccessible
      Femoral Veins.
AB  - An 8.7-year-old boy was affected by exertional dyspnea with cyanosis of the lip
      at 6 years old. Oxygen saturation (SpO2) was 66%. A bidirectional Glenn shunt
      (BGS) was constructed to successfully elevate SpO2 to 88%. Unfortunately, he
      again experienced exertional dyspnea with flagrant cyanosis of the lip at 8.5
      years old. SpO2 decreased to 65%. Echocardiography revealed a dysplastic
      pulmonary valve with severe stenosis. Considering the potential growth of the
      right ventricle and the branch pulmonary arteries, transjugular balloon pulmonary
      valvuloplasty (BPV) through a BGS was performed as a palliative treatment for
      cyanosis in this boy because of inaccessible femoral veins. After gradational
      BPV, the opening of the pulmonary valve was dilated from 2.59 mm to 6.65 mm, the
      pressure gradient decreased from 60 mmHg to 25 mmHg, and the SpO2 increased to
      85%. He became physically active and was free of exertional dyspnea at the 12
      month follow-up. BGS is irrefutably an alternative vascular access through which
      transjugular BPV could be performed to ameliorate cyanosis due to dysplastic
      pulmonary valve stenosis in patients with inaccessible femoral vessels.

PMID- 24103404
TI  - Breast cancer in systemic sclerosis: results of a cross-linkage of an Italian
      Rheumatologic Center and a population-based Cancer Registry and review of the
      literature.
AB  - OBJECTIVE: Increased frequency of few types of cancer in systemic sclerosis (SSc)
      has been reported in the literature; in particular, breast carcinoma has been
      proposed as one of the most frequent malignancy in SSc patients, even though data
      are not univocal. The aim of the present study was to retrospectively evaluate
      the prevalence of breast cancer in our SSc series, compared with sex-/age-matched
      general population of the same geographical area, and the possible correlations
      with SSc features, including X-ray exposure for clinical investigations. A review
      of the world literature about this topic was also done. METHODS: Clinical records
      of 318 consecutive SSc patients, 31 M and 287 F, age 51.5+/-14.5 SD years,
      disease duration 10+/-6.5 SD years, referred to our Rheumatology Unit between
      January 2002 and December 2012 were evaluated. RESULTS: Twelve (3.8%) cases of
      breast cancer were recorded, including 11/287 females (3.8%) and 1/31 (3.2%) male
      patients. Considering the subgroup of 202 SSc patients resident in the Province
      of Modena compared with data of the local Tumor Registry, the incidence of breast
      cancer observed in our SSc series is significantly higher than expected (SIR 2.1;
      95% interval of confidence: 1.13-3.90; p<0.01). On the whole, the comparison
      between SSc patients with cancer and those without did not show any significant
      differences with regard to SSc clinical features, including the X-ray exposure.
      Of note is the relatively shorter disease duration at the time of breast cancer
      detection (median 2.5years, range 1-21; disease duration of mean 10+/-6.5 SD
      years in the entire cohort). The review of the literature revealed that the
      observed incidence of breast cancer in our case series is comparable to the few
      studies reporting the highest percentages of this malignancy. CONCLUSIONS: A
      significant increase of breast cancer incidence compared to sex-age-matched
      general population from the same geographic area was observed. Moreover, a close
      temporal relationship between SSc and breast cancer onset was found,
      independently from clinical, serological, and instrumental features of SSc. The
      possible pathogenetic link between this systemic autoimmune disease and
      complicating breast cancer, as well as the results of previous studies, are
      discussed.

PMID- 24103405
TI  - Primary care patient willingness for genetic testing for salt-sensitive
      hypertension: a cross sectional study.
AB  - BACKGROUND: The current research into single nucleotide polymorphisms has
      extended the role of genetic testing to the identification of increased risk for
      common medical conditions. Advances in genetic research may soon necessitate
      preparation for the role of genetic testing in primary care medicine. This study
      attempts to determine what proportion of patients would be willing to undergo
      genetic testing for salt-sensitive hypertension in a primary care setting, and
      what factors are related to this willingness. METHODS: A cross-sectional study
      using a self-report questionnaire was conducted among outpatients in primary care
      clinics and hospitals in Japan. The main characteristics measured were education
      level, family medical history, personal medical history, concern about
      hypertension, salt preference, reducing salt intake, and willingness to undergo
      genetic testing for salt-sensitive hypertension. RESULTS: Of 1,932 potential
      participants, 1,457 (75%) responded to the survey. Of the respondents, 726 (50%)
      indicated a willingness to undergo genetic testing. Factors related to this
      willingness were being over 50 years old (adjusted odds ratio [ad-OR] = 1.42, 95%
      Confidence interval = 1.09 - 1.85), having a high level of education (ad-OR:
      1.83, 1.38 - 2.42), having a family history of hypertension (ad-OR: 1.36, 1.09 -
      1.71), and worrying about hypertension (ad-OR: 2.06, 1.59 - 2.68). CONCLUSIONS:
      Half of the primary care outpatients surveyed in this study wanted to know their
      genetic risk for salt-sensitive hypertension. Those who were worried about
      hypertension or had a family history of hypertension were more likely to be
      interested in getting tested. These findings suggest that primary care physicians
      should provide patients with advice on genetic testing, as well as address their
      anxieties and concerns related to developing hypertension.

PMID- 24103406
TI  - First human use of an allogeneic tissue-engineered vascular graft for
      hemodialysis access.
AB  - An arteriovenous fistula is the current gold standard for chronic hemodialysis
      access. Tunneled catheters or synthetic grafts have poorer outcomes and much
      higher risks of infection. This report presents the first clinical use of a
      completely biological, allogeneic, nonliving, and human tissue-engineered
      vascular graft. Tissue-engineered vascular grafts built from allogeneic
      fibroblasts were implanted as shunts in three hemodialysis patients. The tissue
      engineered vascular graft was stored for 9 months, without loss of mechanical
      strength. Implanted grafts showed no signs of degradation or dilation, with time
      points up to 11 months. Results of panel-reactive antibody and cross-reactivity
      tests showed no evidence of immune responses. 

PMID- 24103407
TI  - Open versus endoscopic great saphenous vein harvest for lower extremity
      revascularization of critical limb ischemia.
AB  - OBJECTIVE: This study determined wound complication rates, intervention rates,
      failure mechanisms, patency, limb salvage, and overall survival after lower
      extremity revascularization using open vein harvest (OVH) vs endoscopic vein
      harvest (EVH) for critical limb ischemia. METHODS: A single-institution review
      was conducted of consecutive patients who underwent infrainguinal bypass with a
      single-segment reversed great saphenous vein between 2005 and 2012. RESULTS: A
      total of 251 patients with critical limb ischemia underwent revascularization,
      comprising 153 with OVH and 98 with EVH. The OVH group had a lower mean body mass
      index (26.7 vs 29.9 kg/m(2); P = .001). There were no other differences in
      demographics, comorbidities, medications, smoking, or in the proximal or distal
      anastomotic site. Median operative times were 249 minutes (OVH) vs 316 minutes
      (EVH; P < .001). Median postoperative hospital length of stay was 7 days (OVH) vs
      5 days (EVH; P < .001). Median follow-up was 295 days (OVH) vs 313 days (EVH; P =
      .416). During follow-up, 21 OVH grafts (14%) and 27 EVH grafts (28%) underwent an
      intervention (P = .048). There were a similar number of surgical interventions:
      50% (OVH) vs 61% (EVH; P = .449). Failed grafts had a mean of 1.2 stenoses per
      graft, regardless of harvest method. Median stenosis length was 2.1 cm (OVH) vs
      2.5 cm (EVH; P = .402). At 1 and 3 years, the primary patency was 71% and 52%
      (OVH) vs 58% and 41% (EVH; P = .010), and secondary patency was 88% and 71% (OVH)
      vs 88% and 64% (EVH; P = .266). A secondary patency Cox proportional hazard model
      showed EVH had a hazard ratio of 2.93 (95% confidence interval, 1.03-8.33; P =
      .044). Overall and harvest-related wound complications were 44% and 29% (OVH) vs
      37% and 12% (EVH; P = .226 and P = .002). At 5 years, amputation-free survival
      was 48% (OVH) vs 54% (EVH; P = .305), and limb salvage was 89% (OVH) and 91%
      (EVH; P = .615). CONCLUSIONS: OVH and EVH have similar failure mechanisms, limb
      salvage, amputation-free survival, and overall survival. EVH is associated with
      impaired patency, increased need for intervention, longer operative times,
      shorter hospital stays, and decreased vein harvest site wound complications. OVH
      of the great saphenous vein may provide optimal patency but was not necessarily
      associated with better patient-centered outcomes. Similar limb salvage rates and
      amputation-free survival may justify the use of EVH, despite inferior patency, to
      capture shorter hospital stays and decreased wound complications.

PMID- 24103408
TI  - A rare case of axillobifemoral bypass graft infection caused by Helicobacter
      cinaedi.
AB  - Helicobacter cinaedi infection is rarely encountered in nonimmunocompromised
      patients. We report the case of an 85-year-old man who presented with
      axillobifemoral bypass graft infection caused by Helicobacter cinaedi. The
      patient was not immunocompromised. We successfully treated him by iliac stenting
      of the native iliac artery, with near-total removal of the infected graft. At
      present, 48 months later, the patient is doing well at home, with no evidence of
      infection. To the best of our knowledge, this is the first report of infection of
      a prosthetic graft caused by Helicobacter cinaedi.

PMID- 24103409
TI  - Community walking programs for treatment of peripheral artery disease.
AB  - BACKGROUND: Supervised walking programs offered at medical facilities for
      patients with peripheral artery disease (PAD) and intermittent claudication (IC),
      although effective, are often not used due to barriers, including lack of
      reimbursement and the need to travel to specialized locations for the training
      intervention. Walking programs for PAD patients that occur in community settings,
      such as those outside of supervised settings, may be a viable treatment option
      because they are convenient and potentially bypass the need for supervised
      walking. This review evaluated the various methods and outcomes of community
      walking programs for PAD. METHODS: A literature review using appropriate search
      terms was conducted within PubMed/MEDLINE and the Cochrane databases to identify
      studies in the English language that used community walking programs to treat PAD
      patients with IC. Search results were reviewed, and relevant articles were
      identified that form the basis of this review. The primary outcome was peak
      walking performance on the treadmill. RESULTS: Ten randomized controlled trials
      examining peak walking outcomes in 558 PAD patients demonstrated that supervised
      exercise programs were more effective than community walking studies that
      consisted of general recommendations for patients with IC to walk at home. Recent
      community trials that incorporated more advice and feedback for PAD patients in
      general resulted in similar outcomes, with no differences in peak walking time
      compared with supervised walking exercise groups. CONCLUSIONS: Unstructured
      recommendations for patients with symptomatic PAD to exercise in the community
      are not efficacious. Community walking programs with more feedback and monitoring
      offer improvements in walking performance for patients with claudication and may
      bypass some obstacles associated with facility-based exercise programs.

PMID- 24103410
TI  - Patellar resurfacing versus no resurfacing in two-stage revision of infected
      total knee arthroplasty.
AB  - BACKGROUND: Cartilage debridement and staged reimplantation are the most common
      treatments for infected total knee arthroplasty (TKA). Very few studies have
      focused on the management of primarily non-resurfaced patellae in infected TKA.
      The purpose of this study was to compare the outcomes of patellar resurfacing and
      non-resurfacing in two-stage revision of infected TKA. METHODS: This study
      involved a retrospective comparison of the reinfection rate and clinical outcomes
      of revision TKA patients managed with patellar resurfacing (22 patients, 23
      knees) and patients managed without patellar resurfacing (26 patients) at a
      minimum two-year follow-up. The mean age in the resurfacing group was 69.4years
      old, and the mean age in the non-resurfacing group was 67.3years old. Three
      scales were used in the assessment: the Knee Society Score, Western Ontario and
      McMaster Universities Osteoarthritis Index, and the Anterior Knee Pain Scale.
      RESULTS: Three knees had recurrent infections. All infections occurred in
      patients who had received patellar resurfacing. There were no significant
      differences between groups in clinical results and on the Anterior Knee Pain
      Scale. A lack of patellar resurfacing did not increase recurrence of infection
      and did not result in significant clinical differences compared to patellar
      resurfacing. CONCLUSIONS: This study indicates that preservation of the original
      patellar bone is a feasible option for patellar management in revision of septic
      TKA. LEVEL OF EVIDENCE: Level III, therapeutic study. See the Guidelines for
      Authors for a complete description of levels of evidence.

PMID- 24103411
TI  - Effects of surgical variables in balancing of total knee replacements using an
      instrumented tibial trial.
AB  - BACKGROUND: In total knee surgery, typically the bone cuts are made first to
      produce the correct overall alignment. This is followed by balancing, often using
      spacer blocks to obtain equal parallel gaps in flexion and extension. Recently an
      electronically instrumented tibial trial has been introduced, which measures
      lateral and medial contact forces. The goal of our study was to determine the
      effect of different surgical variables; changing component sizes, modifying bone
      cuts, or ligament releases; on the contact forces, as a method to achieve
      balancing. METHODS: A special rig was designed to fit on a standard operating
      table, on which tests on 10 lower extremity specimens were carried out. After
      making bone cuts for a posterior cruciate retaining knee using a navigation
      system, tibial thickness was determined in extension using the Sag Test.
      Different Surgical Variables were then implemented, and the changes in the
      condylar forces were determined throughout flexion using the Heel Push Test.
      RESULTS: condylar forces were found to consist of gravity forces due to the
      weight of the leg plus forces due to pretension in the collateral ligaments. The
      pretension force averaged 145 N but there was considerable variation because of
      ligament stiffness properties. Balancing from an imbalanced state could be
      achieved with adjustments within only 2 degrees  or 2 mm. CONCLUSION: The
      instrumented tibial trial provided force information which indicated which
      surgical correction options to carry out to achieve balancing. From an initial
      unbalanced state, relatively small changes could produce balancing, indicating
      the sensitivity of the procedure. CLINICAL RELEVANCE: Non-clinical. This study
      will assist in the balancing of the knee at total knee replacement surgery.

PMID- 24103412
TI  - Rapid warming in Tibet, China: public perception, response and coping resources
      in urban Lhasa.
AB  - BACKGROUND: Tibet, average altitude more than 4,000 meters, is warming faster
      than anywhere else in China. The increase in temperatures may aggravate existing
      health problems and lead to the emergence of new risks. However, there are no
      actions being taken at present to protect population health due to limited
      understanding about the range and magnitude of health effects of climate change.
      METHODS: The study was a cross-sectional survey of 619 respondents from urban
      Lhasa, Tibet in August 2012 with the aim to investigate public perceptions of
      risk, heat experiences, and coping resources. RESULTS: Respondents are aware of
      the warming that has occurred in Lhasa in recent years. Over 78% reported that
      rising temperature is either a "very" or "somewhat" serious threat to their own
      health, and nearly 40% reported they had experienced heat-related symptoms. Sex,
      age, education and income influenced perceived risks, health status, and heat
      experience. The vast majority of respondents reported that they had altered their
      behaviour on hot summer days. Bakuo, a sub-district at the city center, is
      considered especially vulnerable to heat because of sparse vegetation, high
      population density, poor dwelling conditions and a high proportion of low-income
      population. However, neighborhood social ties were stronger in Bakuo than other
      study locations. CONCLUSIONS: The study suggests that actions are needed now to
      minimize downside effects of rapid warming in Tibet, because of increasing human
      exposure to high temperatures and uneven distribution of the resources needed to
      cope.

PMID- 24103413
TI  - Prenatal mercury exposure and infant birth weight in the Norwegian Mother and
      Child Cohort Study.
AB  - OBJECTIVE: To examine the association between calculated maternal dietary
      exposure to Hg in pregnancy and infant birth weight in the Norwegian Mother and
      Child Cohort Study (MoBa). DESIGN: Exposure was calculated with use of a
      constructed database of Hg in food items and reported dietary intake during
      pregnancy. Multivariable regression models were used to explore the association
      between maternal Hg exposure and infant birth weight, and to model associations
      with small-for-gestational-age offspring. SETTING: The study is based on data
      from MoBa. SUBJECTS: The study sample consisted of 62 941 women who answered a
      validated FFQ which covered the habitual diet during the first five months of
      pregnancy. RESULTS: Median exposure to Hg was 0.15 MUg/kg body weight per week
      and the contribution from seafood intake was 88 % of total Hg exposure. Women in
      the highest quintile compared with the lowest quintile of Hg exposure delivered
      offspring with 34 g lower birth weight (95 % CI -46 g, -22 g) and had an
      increased risk of giving birth to small-for-gestational-age offspring, adjusted
      OR = 1.19 (95 % CI 1.08, 1.30). Although seafood intake was positively associated
      with increased birth weight, stratified analyses showed negative associations
      between Hg exposure and birth weight within strata of seafood intake.
      CONCLUSIONS: Although seafood intake in pregnancy is positively associated with
      birth weight, Hg exposure is negatively associated with birth weight. Seafood
      consumption during pregnancy should not be avoided, but clarification is needed
      to identify at what level of Hg exposure this risk might exceed the benefits of
      seafood.

PMID- 24103414
TI  - Control of thumb force using surface functional electrical stimulation and muscle
      load sharing.
AB  - BACKGROUND: Stroke survivors often have difficulties in manipulating objects with
      their affected hand. Thumb control plays an important role in object
      manipulation. Surface functional electrical stimulation (FES) can assist
      movement. We aim to control the 2D thumb force by predicting the sum of
      individual muscle forces, described by a sigmoidal muscle recruitment curve and a
      single force direction. METHODS: Five able bodied subjects and five stroke
      subjects were strapped in a custom built setup. The forces perpendicular to the
      thumb in response to FES applied to three thumb muscles were measured. We
      evaluated the feasibility of using recruitment curve based force vector maps in
      predicting output forces. In addition, we developed a closed loop force
      controller. Load sharing between the three muscles was used to solve the
      redundancy problem having three actuators to control forces in two dimensions.
      The thumb force was controlled towards target forces of 0.5 N and 1.0 N in
      multiple directions within the individual's thumb work space. Hereby, the
      possibilities to use these force vector maps and the load sharing approach in
      feed forward and feedback force control were explored. RESULTS: The force vector
      prediction of the obtained model had small RMS errors with respect to the actual
      measured force vectors (0.22 +/- 0.17 N for the healthy subjects; 0.17 +/- 0.13 N
      for the stroke subjects). The stroke subjects showed a limited work range due to
      limited force production of the individual muscles. Performance of feed forward
      control without feedback, was better in healthy subjects than in stroke subjects.
      However, when feedback control was added performances were similar between the
      two groups. Feedback force control lead, especially for the stroke subjects, to a
      reduction in stationary errors, which improved performance. CONCLUSIONS: Thumb
      muscle responses to FES can be described by a single force direction and a
      sigmoidal recruitment curve. Force in desired direction can be generated through
      load sharing among redundant muscles. The force vector maps are subject specific
      and also suitable in feedforward and feedback control taking the individual's
      available workspace into account. With feedback, more accurate control of muscle
      force can be achieved.

PMID- 24103415
TI  - The association between adult mortality risk and family history of longevity: the
      moderating effects of socioeconomic status.
AB  - Studies consistently show that increasing levels of socioeconomic status (SES)
      and having a familial history of longevity reduce the risk of mortality. But do
      these two variables interact, such that individuals with lower levels of SES, for
      example, may experience an attenuated longevity penalty by virtue of having long
      lived relatives? This article examines this interaction by analysing survival
      past age 40 based on data from the Utah Population Database on an extinct cohort
      of men born from the years 1840 to 1909. Cox proportional hazards regression and
      logistic regression are used to test for the main and interaction mortality
      effects of SES and familial excess longevity (FEL), a summary measure of an
      individual's history of longevity among his or her relatives. This research finds
      that the mortality hazard rate for men in the top 15th percentile of occupational
      status decreases more as FEL increases than it does among men in the bottom 15th
      percentile. In addition, the mortality hazard rate among farmers decreases more
      as FEL increases than it does for non-farmers. With a strong family history of
      longevity as a proxy for a genetic predisposition, this research suggests that a
      gene-environment interaction occurs whereby the benefits of familial excess
      longevity are more available to those who have occupations with more autonomy and
      greater economic resources and/or opportunities for physical activity.

PMID- 24103416
TI  - Validation of the Korean version of the Acupuncture Expectancy Scale.
AB  - OBJECTIVES: Expectancy has been shown to affect patients' responses to
      acupuncture therapy. However, no validated measure of expectancy for acupuncture
      is available in the Korean language. The Acupuncture Expectancy Scale (AES), a 4
      item self-reporting questionnaire, is the validated instrument for measuring
      expectancies regarding acupuncture therapy. We translated the AES into Korean and
      examined its test-retest reliability and construct validity. METHODS: The AES was
      translated using a forward and backward translation procedure. Internal
      consistency was assessed in 275 participants with item-total correlations.
      Construct validity was also assessed by performing principal component analysis
      and correlating scores on the scale with the participants' intention to receive
      acupuncture therapy. Test-retest reliability was assessed in 33 participants by
      calculating Cronbach's alpha and Spearman rank correlation coefficients. RESULTS:
      Internal consistency was high (Cronbach's alpha=0.910). Principal component
      analysis showed that expectancy of acupuncture treatment accounted for 79.2% of
      the variance. The AES was positively correlated with participants' intention to
      receive acupuncture treatment (r=0.695, p<0.001). Test-retest reliability in 33
      of the 275 participants was adequate, with the Spearman rank correlation
      coefficient ranging from 0.500 to 0.737 (p<0.001). CONCLUSIONS: The Korean
      version of the AES is a valid and reliable instrument for measuring patients'
      expectancies regarding acupuncture treatment in the Korean population.

PMID- 24103418
TI  - Dairy intensification in developing countries: effects of market quality on farm
      level feeding and breeding practices.
AB  - Smallholder dairy production represents a promising income generating activity
      for poor farmers in the developing world. Because of the perishable nature of
      milk, marketing arrangements for collection, distribution and sale are important
      for enhanced livelihoods in the smallholder dairy sector. In this study we
      examined the relationship between market quality and basic feeding and breeding
      practices at farm level. We define market quality as the attractiveness and
      reliability of procurement channels and associated input supply arrangements. We
      took as our study countries, India with its well-developed smallholder dairy
      sector, and Ethiopia where the smallholder dairy industry has remained relatively
      undeveloped despite decades of development effort. We conducted village surveys
      among producer groups in 90 villages across three States in India and two Regions
      in Ethiopia. Producer groups were stratified according to three levels of market
      quality - high, medium and low. Data showed that diet composition was relatively
      similar in India and Ethiopia with crop residues forming the major share of the
      diet. Concentrate feeding tended to be more prominent in high market quality
      sites. Herd composition changed with market quality with more dairy (exotic)
      cross-bred animals in high market quality sites in both India and Ethiopia. Cross
      bred animals were generally more prominent in India than Ethiopia. Herd
      performance within breed did not change a great deal along the market quality
      gradient. Parameters such as calving interval and milk yield were relatively
      insensitive to market quality. Insemination of cross-bred cows was predominantly
      by artificial insemination (AI) in India and accounted for around half of cross
      bred cow inseminations in Ethiopia. Data on perceptions of change over the last
      decade indicated that per herd and per cow productivity are both increasing in
      high market quality sites with a more mixed picture in medium and low-quality
      sites. Similarly dairy-derived income is on the increase in high market quality
      sites. This is accompanied by a strong increase in stall feeding at the expense
      of grazing. The study indicates that the first constraint to intensification of
      dairy production in Ethiopia is the genetic quality of the herd. There is less
      scope for improved AI provision in India since the cross-bred herd is mainly
      serviced by AI already. However, as for Ethiopia, there is considerable scope for
      closing yield gaps in India through improved feed use and supply. Results
      strongly show that well-developed markets with good procurement arrangements are
      key for sustainable dairy intensification. 

PMID- 24103417
TI  - Color signals through dorsal and ventral visual pathways.
AB  - Explanations for color phenomena are often sought in the retina, lateral
      geniculate nucleus, and V1, yet it is becoming increasingly clear that a complete
      account will take us further along the visual-processing pathway. Working out
      which areas are involved is not trivial. Responses to S-cone activation are often
      assumed to indicate that an area or neuron is involved in color perception.
      However, work tracing S-cone signals into extrastriate cortex has challenged this
      assumption: S-cone responses have been found in brain regions, such as the middle
      temporal (MT) motion area, not thought to play a major role in color perception.
      Here, we review the processing of S-cone signals across cortex and present
      original data on S-cone responses measured with fMRI in alert macaque, focusing
      on one area in which S-cone signals seem likely to contribute to color
      (V4/posterior inferior temporal cortex) and on one area in which S signals are
      unlikely to play a role in color (MT). We advance a hypothesis that the S-cone
      signals in color-computing areas are required to achieve a balanced neural
      representation of perceptual color space, whereas those in noncolor-areas provide
      a cue to illumination (not luminance) and confer sensitivity to the chromatic
      contrast generated by natural daylight (shadows, illuminated by ambient sky,
      surrounded by direct sunlight). This sensitivity would facilitate the extraction
      of shape-from-shadow signals to benefit global scene analysis and motion
      perception. 

PMID- 24103419
TI  - Incident atrial fibrillation among Asians, Hispanics, blacks, and whites.
AB  - BACKGROUND: Because the association between atrial fibrillation (AF) and race has
      only been rigorously compared in population-based studies that dichotomized
      participants as white or black, it is unclear whether white race confers elevated
      AF risk or black race affords AF protection. METHODS AND RESULTS: The Healthcare
      Cost and Utilization Project was used to identify patients receiving hospital
      based care in California between January 1, 2005 and December 31, 2009. The
      association between race and incident AF was examined using Cox proportional
      hazards models. Interaction analyses were performed to elucidate the mechanism
      underlying the race-AF association. Among 13 967 949 patients, 375 318 incident
      AF episodes were observed over a median 3.2 (interquartile range 1.8-4.3) years.
      In multivariable Cox models adjusting for patient demographics and established AF
      risk factors, blacks (hazard ratio, 0.84; 95% confidence interval, 0.82-0.85;
      P<0.001), Hispanics (hazard ratio, 0.78; 95% confidence interval, 0.77-0.79;
      P<0.001), and Asians (hazard ratio, 0.78; 95% confidence interval, 0.77-0.79;
      P<0.001) each exhibited a lower AF risk compared with whites. AF risk among
      whites was disproportionately higher in the absence of acquired cardiovascular
      risk factors and diminished or reversed in the presence of comorbid diseases.
      Although Hispanics and Asians also had a lower adjusted risk of incident atrial
      flutter compared with whites, the risk of flutter was significantly higher among
      blacks. CONCLUSIONS: In a large hospital-based cohort, whites have an increased
      risk of AF whether compared with blacks, Asians, or Hispanics. The heightened AF
      risk among whites is most pronounced in the absence of cardiovascular
      comorbidities.

PMID- 24103420
TI  - Crystal structure of native and a mutant of Lampyris turkestanicus luciferase
      implicate in bioluminescence color shift.
AB  - Firefly bioluminescence reaction in the presence of Mg(2+), ATP and molecular
      oxygen is carried out by luciferase. The luciferase structure alterations or
      modifications of assay conditions determine the bioluminescence color of firefly
      luciferase. Among different beetle luciferases, Phrixothrix hirtus railroad worm
      emits either yellow or red bioluminescence color. Sequence alignment analysis
      shows that the red-emitter luciferase from Phrixothrix hirtus has an additional
      arginine residue at 353 that is absent in other firefly luciferases. It was
      reported that insertion of Arg in an important flexible loop350-359 showed
      changes in bioluminescence color from green to red and the optimum temperature
      activity was also increased. To explain the color tuning mechanism of firefly
      luciferase, the structure of native and a mutant (E354R/356R/H431Y) of Lampyris
      turkestanicus luciferase is determined at 2.7A and 2.2A resolutions,
      respectively. The comparison of structure of both types of Lampyris turkestanicus
      luciferases reveals that the conformation of this flexible loop is significantly
      changed by addition of two Arg in this region. Moreover, its surface
      accessibility is affected considerably and some ionic bonds are made by addition
      of two positive charge residues. Furthermore, we noticed that the hydrogen
      bonding pattern of His431 with the flexible loop is changed by replacing this
      residue with Tyr at this position. Juxtaposition of a flexible loop (residues 351
      359) in firefly luciferase and corresponding ionic and hydrogen bonds are
      essential for color emission. 

PMID- 24103421
TI  - Obese but not lean adolescents spontaneously decrease energy intake after
      intensive exercise.
AB  - BACKGROUND: Acute intensive exercise has been shown to induce a decreased
      subsequent daily energy intake in obese adolescents without altering the
      subjective appetite feelings. It is however unclear whether or not those
      nutritional adaptations to acute exercise are affected by the adolescents' weight
      status. The aim of this study was to compare the energy intake and macronutrient
      preferences, appetite feeling and energy expenditure response to acute exercise
      between lean and obese adolescents. METHODS: Ten obese and nine normal weight 12
      15year old adolescents randomly completed a session with a 30minute cycling
      exercise at 75% VO2max and a sedentary session. During both sessions energy
      expenditure was assessed using Armband, ad libitum energy intake measured by
      weighing at both lunch and dinner time and appetite feelings assessed using
      visual analog scales. RESULTS: Daily, morning and afternoon energy expenditure
      were significantly higher in obese than in normal weight adolescents (p<0.001).
      Total energy expenditure was significantly higher during EX (1086+/-157kcal)
      compared to SED (853+/-154kcal) in lean (p<0.05) but not significantly different
      in obese (respectively 1865+/-222 and 1803+/-232kcal). Afternoon energy
      expenditure was significantly lower during EX compare to SED in obese (p<0.05)
      but not in normal weight adolescents. Lunch, dinner and total daily energy intake
      were significantly reduced after the exercise session in obese (p>0.05) but not
      in lean adolescents. No group or condition effects were observed on subjective
      appetite feelings. DISCUSSION: Post exercise spontaneous energy intake and energy
      expenditure are reduced in obese but not in normal weight adolescents, without
      appetite feeling changes. Acute exercise may have a greater impact on energy
      balance through the induced decreased energy intake in the absence of significant
      change in energy expenditure in obese youth.

PMID- 24103422
TI  - Inhibition of Mcl-1 expression by citrate enhances the effect of Bcl-xL
      inhibitors on human ovarian carcinoma cells.
AB  - The inhibition of two major anti-apoptotic proteins, Bcl-xL and Mcl-1, appears
      essential to destroy chemoresistant cancer cells. We have studied their
      concomitant inhibition, using ABT 737 or siRNA targeting XL1 and citrate, a
      molecule which reduces the expression level of Mcl-1.Two cisplatin-chemoresistant
      ovarian cell lines (SKOV3 and IGROV1-R10) were exposed to ABT 737 or siRNA
      targeting XL1 and citrate at various individual concentrations, or combined. Cell
      proliferation, cell cycle repartition and nuclear staining with DAPI were
      recorded. Western blot analyses were performed to detect various proteins implied
      in apoptotic cell death pathways.Mcl-1 expression was barely reduced when cells
      were exposed to citrate alone, whereas a mild reduction was observed after ABT
      737 treatment. Concomitant inhibition of Bcl-xL and Mcl-1 using ABT 737 or siXL1
      associated with citrate was far more effective in inhibiting cell proliferation
      and inducing cell death than treatment alone.Given that few, if any, specific
      inhibitors of Mcl-1 are currently available, anti-glycolytic agents such as
      citrate could be tested in association with synthetic inhibitors of Bcl-xL. 

PMID- 24103423
TI  - A birth cohort study of viral infections in Vietnamese infants and children:
      study design, methods and characteristics of the cohort.
AB  - BACKGROUND: In Ho Chi Minh City, Vietnam, more than one-third of admissions to
      the two paediatric hospitals are attributable to four infectious syndromes:
      dengue, diarrhoeal disease, acute respiratory infection, and hand, foot and mouth
      disease. We have established a large prospective birth cohort study to
      investigate individual, environmental, virological, and immunological
      determinants of infection and disease in infants. Specific research questions are
      focused on the role of maternal antibody in protection against infection in
      infancy, and the adaptive immune response to vaccination and natural infection.
      This paper presents the cohort design, methods, and baseline characteristics of
      the participants enrolled in the first two years. METHODS/DESIGN: Women are
      enrolled prior to delivery at one hospital in each of two catchment areas: an
      urban district in central HCMC, and a mixed urban/rural district in the Mekong
      Delta 150 km southwest of HCMC. Infants are enrolled within 3 days of birth, and
      maternal and cord blood samples are collected. Routine blood samples and data on
      growth, health status and vaccinations are collected from infants at scheduled
      visits at 4, 9 and 12 months. Clinical data and specimens are collected from
      infants presenting at a study clinic, or admitted to hospital, with any of the
      the four infectious syndromes of interest. DISCUSSION: In four years since since
      the study began in July 2009, >6400 infants have been enrolled, and enrolment is
      ongoing. Attrition is low: 84% of participants have completed the full 12-month
      follow-up period. Baseline characteristics of the first 4300 enrollees are
      presented here. We have demonstrated the feasibility of establishing a large
      prospective study of infectious diseases in infancy in a resource-limited
      setting, with minimal loss to follow-up. Our linked socio-demographic, clinical
      and laboratory data will help elucidate the viral aetiology and epidemiology of
      common infectious diseases of infancy, and can inform the implemention of
      existing and future vaccines. This study furthermore provides a platform to which
      additional endpoints could be added in the future.

PMID- 24103424
TI  - Characteristics of cases with unknown stage prostate cancer in a population-based
      cancer registry.
AB  - BACKGROUND: The New South Wales Central Cancer Registry (NSW CCR) is the only
      population-based cancer registry in Australia that has routinely collected
      summary stage at diagnosis since its inception in 1972. However, a large
      proportion of prostate cancer cases have "unknown" stage recorded by the
      registry. We investigated the characteristics of prostate cancer cases with
      "unknown" stage recorded by the NSW CCR, and examined survival for this group.
      METHODS: Data were obtained from the NSW CCR for all first primary prostate
      cancer cases diagnosed in 1999-2007. Summary stage was recorded as localised,
      regional, distant or "unknown". Associations between disease stage and patient
      characteristics (age, place of residence at diagnosis, year of diagnosis and
      country of birth) and prostate cancer specific survival were investigated using
      multivariable logistic regression and Cox proportional hazards models
      respectively. RESULTS: Of 39852 prostate cancer cases, 41.8% had "unknown" stage
      recorded by the NSW CCR. This proportion decreased significantly over time,
      increased with increasing age at diagnosis and was higher for those living in
      socio-economically disadvantaged areas. The proportion with "unknown" stage
      varied across area health services. Prostate cancer specific survival for cases
      with "unknown" stage was significantly poorer than for those with localised stage
      but better than for those with regional or distant stage. CONCLUSIONS:
      Researchers or others using cancer registry stage data to examine prostate cancer
      outcomes need to consider the differences between cases with "unknown" stage at
      diagnosis and those with known stage recorded by the registry, and what impact
      this may have on their results.

PMID- 24103425
TI  - A potentially functional polymorphism in the promoter region of let-7 family is
      associated with survival of hepatocellular carcinoma.
AB  - BACKGROUND: The let-7 family plays a vital role in the normal cellular activity
      of liver cells and the carcinogenesis of hepatocellular carcinoma (HCC). In the
      previous study, we have detected the association between single nucleotide
      polymorphisms (SNPs) in the promoter region of let-7 and susceptibility to HCC.
      However, it is still unknown whether these polymorphisms are associated with HCC
      prognosis. METHODS: We investigated the effect of two potentially functional SNPs
      in the promoter region of let-7 family, rs10877887 (T>C) and rs13293512 (T>C), on
      the overall survival of 331 HCC patients. Log-rank test and Cox proportional
      hazard models were used for the survival analyses. RESULTS: We found that HCC
      patients carrying the C allele of rs10877887 had a significantly increased death
      risk (adjusted HR=1.22, 95%CI=1.02-1.47, P=0.03 in the additive model), compared
      to those with T allele. In the stratified analysis, the risk effect was evident
      in HCC patients with Barcelona Clinic Liver Cancer (BCLC) stage B (adjusted
      HR=1.24, 95%CI=1.02-1.51, P=0.03) and in those who received chemotherapy or
      intervention (adjusted HR=1.25, 95%CI=1.02-1.53, P=0.04). CONCLUSIONS: Our
      results suggest that rs10877887 in the promoter region of let-7 may be a
      prognostic biomarker for HCC patients, which need the validation from other
      larger studies in different populations.

PMID- 24103427
TI  - Synthesis and antimycobacterial activity of isoniazid derivatives from renewable
      fatty acids.
AB  - This work describes the synthesis of a series of fatty acid hydrazide derivatives
      of isoniazid (INH). The compounds were tested against Mycobacterium tuberculosis
      H37Rv (ATCC 27294) as well as INH-resistant (ATCC 35822 and 1896 HF) and
      rifampicin-resistant (ATCC 35338) M. tuberculosis strains. The fatty acid
      derivatives of INH showed high antimycobacterial potency against the studied
      strains, which is desirable for a pharmaceutical compound, suggesting that the
      increased lipophilicity of isoniazid plays an important role in its
      antimycobacterial activity. 

PMID- 24103426
TI  - Reversal of chemosensitivity and induction of cell malignancy of a non-malignant
      prostate cancer cell line upon extracellular vesicle exposure.
AB  - BACKGROUND: Extracellular vesicle (EV) trafficking is a fundamental cellular
      process that occurs in cells and is required for different aspects of
      pathophysiology. EV trafficking leads to changes in cellular function including
      apoptosis, angiogenesis and proliferation required for increased tumor formation.
      RESULTS: We report several phenotypic changes mediated by EVs isolated from non
      malignant and malignant prostate cells as well as patient biopsied prostate tumor
      samples. EVs can reverse the resistance of prostate cancer cells to camptothecin
      EVs isolated from non-malignant PrECs (Prostate Epithelial Cells) can reverse
      soft agar colony formation of malignant DU145 cells, with the reciprocal effect
      observed. Isolation of EVs from 2 Gleason grade 8 prostate cancer patients
      significantly induced soft agar colony formation of non-malignant PrECs. We have
      identified proteins via antibody and Mass spectrometry analysis that may be
      responsible for the phenotypic changes. Mass spectrometry analysis of protein
      lysates using ProteoIQ revealed protein candidates associated with gene ontology
      annotations that may be responsible for this phenotypic change. Ingenuity Pathway
      Analysis was used to identify statistically relevant canonical pathways and
      functions associated the protein IDs and expression values obtained using
      ProteoIQ. Western blot analysis confirmed the increase of 14-3-3 zeta, pRKIP and
      prohibitin protein levels in PrEC cells co-cultured with patient EVs. 14-3-3
      proteins were also found as common proteins of 3 other Gleason grade 8 patients.
      CONCLUSION: Our study provides a rational basis to further investigate putative
      proteins, such as 14-3-3 and prohibitin and genetic factors that may be
      responsible for phenotypic changes that are associated with prostate cancer
      progression.

PMID- 24103428
TI  - Benzenesulfonamides with pyrimidine moiety as inhibitors of human carbonic
      anhydrases I, II, VI, VII, XII, and XIII.
AB  - Two groups of benzenesulfonamide derivatives, bearing pyrimidine moieties, were
      designed and synthesized as inhibitors of carbonic anhydrases (CA). Their binding
      affinities to six recombinant human CA isoforms I, II, VI, VII, XII, and XIII
      were determined by the thermal shift assay (TSA). The binding of several
      inhibitors was measured by isothermal titration calorimetry (ITC). Direct
      demonstration of compound inhibition was achieved by determining the inhibition
      constant by stopped-flow CO2 hydration assay. The most potent compounds
      demonstrated selectivity towards isoform I and affinities of 0.5 nM. The crystal
      structures of selected compounds in complex with CA II, XII, and XIII were
      determined to atomic resolution. Compounds described here were compared with
      previously published pyrimidinebenzenesulfonamides.(1) Systematic structure
      activity analysis of 40 compound interactions with six isoforms yields clues for
      the design of compounds with greater affinities and selectivities towards target
      CA isoforms.

PMID- 24103429
TI  - Quinazolinecarboline alkaloid evodiamine as scaffold for targeting topoisomerase
      I and sirtuins.
AB  - This paper reports the synthesis of a series of evodiamine derivatives. We
      assayed the ability to inhibit cell growth on three human tumour cell lines
      (H460, MCF-7 and HepG2) and we evaluated the capacity to interfere with the
      catalytic activity of topoisomerase I both by the relaxation assay and the
      occurrence of the cleavable complex. Moreover, whose effect on sirtuins 1, 2 and
      3 was investigated. Finally, molecular docking analyses were performed in an
      attempt to rationalize the biological results. 

PMID- 24103430
TI  - Inhibition of human carbonic anhydrase isoforms I-XIV with sulfonamides
      incorporating fluorine and 1,3,5-triazine moieties.
AB  - Reaction of cyanuryl fluoride with sulfanilamide or 4
      aminoethylbenzenesulfonamide afforded triazinyl-substituted benzenesulfonamides
      incorporating fluorine, which were further derivatized by reaction with amines,
      amino alcohols, amino acids or amino acid esters. Inhibition studies of all the
      human (h) carbonic anhydrase (CA, EC 4.2.1.1) isoforms, hCA I-XIV with these
      compounds revealed that they show moderate-weak inhibition of hCA III, IV, VA and
      XIII, rather moderate inhibition against hCA I, VI, and IX, and excellent
      inhibition of the physiologically relevant hCA II, VII and XII. The inhibition
      profile of these fluorine containing triazinyl sulfonamides is thus very
      different from the corresponding analogs incorporating chlorine, which were
      previously investigated as inhibitors of some of these enzymes. 

PMID- 24103431
TI  - Developmental changes in the acute ethanol sensitivity of glutamatergic and
      GABAergic transmission in the BNST.
AB  - Glutamatergic and GABAergic transmission undergo significant changes during
      adolescence. Receptors for both of these transmitters (NMDAR, and GABAA) are
      known to be key targets for the acute effects of ethanol in adults. The current
      study set out to investigate the acute effects of ethanol on both NMDAR-mediated
      excitatory transmission and GABAergic inhibitory transmission within the bed
      nucleus of the stria terminalis (BNST) across age. The BNST is an area of the
      brain implicated in the negative reinforcing properties associated with alcohol
      dependence, and the BNST plays a critical role in stress-induced relapse.
      Therefore, assessing the developmental regulation of ethanol sensitivity in this
      key brain region is important to understanding the progression of ethanol
      dependence. To do this, whole-cell recordings of isolated NMDAR-evoked excitatory
      postsynaptic currents (eEPSCs) or evoked GABAergic inhibitory postsynaptic
      currents (eIPSCs) were performed on BNST neurons in slices from 4- or 8-week-old
      male C57BL/6J mice. Ethanol (50 mm) produced greater inhibition of NMDAR-eEPSCs
      in adolescent mice than in adult mice. This enhanced sensitivity in adolescence
      was not a result of shifts in function of the GluN2B subunit of the NMDAR,
      measured by Ro25-6981 inhibition and decay kinetics measured across age.
      Adolescent mice also exhibited greater ethanol sensitivity of GABAergic
      transmission, as ethanol (50 mm) enhanced eIPSCs in the BNST of adolescent but
      not adult mice. Collectively, this work illustrates that a moderate dose of
      ethanol produces greater inhibition of transmission in the BNST (through greater
      excitatory inhibition and enhancement of inhibitory transmission) in adolescents
      compared to adults. Given the role of the BNST in alcohol dependence, these
      developmental changes in acute ethanol sensitivity could accelerate
      neuroadaptations that result from chronic ethanol use during the critical period
      of adolescence.

PMID- 24103433
TI  - Enantioselective determination of 3-n-butylphthalide (NBP) in human plasma by
      liquid chromatography on a teicoplanin-based chiral column coupled with tandem
      mass spectrometry.
AB  - A novel and sensitive liquid chromatography-tandem mass spectrometry (LC-MS/MS)
      method was developed and validated to determine the exposure of 3-n
      butylphthalide (NBP) enantiomers in human plasma. The NBP enantiomers were
      extracted from human plasma using methyl tert-butyl ether. The baseline
      separation of R-(+)-NBP and S-(-)-NBP was achieved within 11.0min using a
      teicoplanin-based Astec Chirobiotic T column (250mm*4.6mm i.d., 5MUm) under
      isocratic conditions at a flow rate of 0.6mL/min. The selection of the chiral
      stationary phase and the effect of the mobile phase composition on the resolution
      of the enantiomers were discussed. The selectivity, linearity, precision,
      accuracy, matrix effect, recovery, and stability were evaluated under optimized
      conditions. The LC-MS/MS method using 200MUL of human plasma was linear over the
      concentration range of 5.00-400ng/mL for each enantiomer. The lower limit of
      quantification (LLOQ) for both enantiomers was 5.00ng/mL. The intra- and inter
      assay precision values of the replicated quality control samples were within 8.0%
      for each enantiomer. The mean accuracy values for the quality control samples
      were within +/-6.1% of the nominal values for R-(+)-NBP and S-(-)-NBP. No chiral
      inversion was observed during sample storage, preparation, and analysis. The
      method proved suitable for enantioselective pharmacokinetic studies of NBP after
      an oral administration of a therapeutic dose of racemic NBP. 

PMID- 24103432
TI  - Antiviral activity of carnosic acid against respiratory syncytial virus.
AB  - BACKGROUND: Human respiratory syncytial virus (hRSV) is a leading cause of severe
      lower respiratory infection and a major public health threat worldwide. To date,
      no vaccine or effective therapeutic agent has been developed. In a screen for
      potential therapeutic agents against hRSV, we discovered that an extract of
      Rosmarinus officinalis exerted a strong inhibitory effect against hRSV infection.
      Subsequent studies identified carnosic acid as a bioactive constituent
      responsible for anti-hRSV activity. Carnosic acid has been shown to exhibit
      potent antioxidant and anti-cancer activities. Anti-RSV activity of carnosic acid
      was further investigated in this study. METHODS: Effects of extracts from various
      plants and subfractions from R. officinalis on hRSV replication were determined
      by microneutralization assay and plaque assay. Several constituents were isolated
      from ethyl acetate fraction of R. officinalis and their anti-RSV activities were
      assessed by plaque assay as well as reverse-transcription quantitative PCR to
      determine the synthesis of viral RNAs. RESULTS: Among the tested bioactive
      constituents of R. officinalis, carnosic acid displayed the most potent anti-hRSV
      activity and was effective against both A- and B-type viruses. Carnosic acid
      efficiently suppressed the replication of hRSV in a concentration-dependent
      manner. Carnosic acid effectively suppressed viral gene expression without
      inducing type-I interferon production or affecting cell viability, suggesting
      that it may directly affect viral factors. A time course analysis showed that
      addition of carnosic acid 8 hours after infection still effectively blocked the
      expression of hRSV genes, further suggesting that carnosic acid directly
      inhibited the replication of hRSV. CONCLUSIONS: The current study demonstrates
      that carnosic acid, a natural compound that has already been shown to be safe for
      human consumption, has anti-viral activity against hRSV, efficiently blocking the
      replication of this virus. Carnosic acid inhibited both A- and B- type hRSV,
      while it did not affect the replication of influenza A virus, suggesting that its
      antiviral activity is hRSV-specific. Collectively, this study suggests the need
      for further evaluation of carnosic acid as a potential treatment for hRSV.

PMID- 24103434
TI  - The application of axial superficial temporal artery island flap for repairing
      the defect secondary to the removal of the lower eyelid basal cell carcinoma.
AB  - Our aim was to investigate the repair of the defect that follows excision of a
      basal cell carcinoma (BCC) of the lower eyelid. Skin projections of the
      superficial temporal artery and its frontal branches were marked using Doppler
      ultrasonography. The lesion was excised with 0.5-1.5cm margins. Frozen sections
      were taken to clarify the diagnosis. The frontal flap was designed according to
      the preoperative labelling, and was 0.5cm larger than the defect. The pedicle was
      1.0-1.5cm longer than the distance between the pedicle and the defect, and the
      width of the pedicle was 3cm. If the lesion affected the full thickness of the
      lower eyelid, a conjunctival flap was sutured with the flap. A skin graft was
      applied when the defect was large. Such defects have been repaired successfully
      in 10 patients. There was no secondary defect or ectropion postoperatively. The
      superficial temporal artery frontal branch island flap is a satisfactory method
      for the repair of a defect secondary to a BCC of the lower eyelid.

PMID- 24103435
TI  - Waist:height ratio: a superior index in estimating cardiovascular risks in
      Turkish adults.
AB  - OBJECTIVE: To determine the best anthropometric measurement among waist: height
      ratio (WHtR), BMI, waist:hip ratio (WHR) and waist circumference (WC) associated
      with high CHD risk in adults and to define the optimal cut-off point for WHtR.
      DESIGN: Population-based cross-sectional study. SETTING: Balcova, Izmir, Turkey.
      SUBJECTS: Individuals (n 10 878) who participated in the baseline survey of the
      Heart of Balcova Project. For each participant, 10-year coronary event risk
      (Framingham risk score) was calculated using data on age, sex, smoking status,
      blood pressure, serum lipids and diabetes status. Participants who had risk
      higher than 10 % were defined as 'medium or high risk'. RESULTS: Among the
      participants, 67.7% were female, 38.2% were obese, 24.5% had high blood pressure,
      9.2% had diabetes, 1.5% had undiagnosed diabetes (>=126 mg/dl), 22.0% had high
      total cholesterol and 45.9% had low HDL-cholesterol. According to Framingham risk
      score, 32.7% of them had a risk score higher than 10 %. Those who had medium or
      high risk had significantly higher mean BMI, WHtR, WHR and WC compared with those
      at low risk. According to receiver-operating characteristic curves, WHtR was the
      best and BMI was the worst indicator of CHD risk for both sexes. For both men and
      women, 0.55 was the optimal cut-off point for WHtR for CHD risk. CONCLUSIONS: BMI
      should not be used alone for evaluating obesity when estimating cardiometabolic
      risks. WHtR was found to be a successful measurement for determining
      cardiovascular risks. A cut-off point of '0.5' can be used for categorizing WHtR
      in order to target people at high CHD risk for preventive actions.

PMID- 24103436
TI  - Lessons from history of socioeconomic improvements: a new approach to treating
      multi-drug-resistant tuberculosis.
AB  - This study investigated the trends in tuberculosis mortality through time in
      Switzerland. Information on the decline in mortality before chemotherapies were
      introduced may be useful in developing countries where drug-resistant
      tuberculosis is now becoming a major problem. Swiss data were collected from
      historical records and comparative data were obtained from the literature for
      England and Wales, New York, Japan, Brazil and Sierra Leone. Logistic curves were
      fitted to examine the rate of decline before introduction of pharmacotherapies
      and these show that the decline would have continued without the introduction of
      chemical therapies, including antibiotics. In Switzerland, England and Wales and
      New York, the decline had occurred long before the introduction of specific anti
      tuberculosis agents. In Brazil and Japan, chemical therapy was co-incident with
      the decline in tuberculosis mortality rates. Overall, it is suggested that the
      effective control of tuberculosis can be achieved through a combination of
      chemical interventions, conservative therapy (rest, good nutrition, ventilation,
      etc.) as well as public health interventions addressing hygiene, nutrition,
      reducing exposure to infections and educating the population about tuberculosis.

PMID- 24103437
TI  - The environmental characteristics of usage of coal gangue in bricking-making: a
      case study at Huainan, China.
AB  - The behaviors of natural radionuclides and toxic elements during coal gangue
      brick making processes are described. A simulation experiment of coal gangue
      brick firing was carried out to evaluate the enrichments of natural radionuclides
      and volatilizations of elements. Simultaneous sampling of coal gangue and
      corresponding combustion product (slag) was performed. The radioactivities of the
      radionuclide were determined by high-purity germanium gamma ray spectrometer, and
      the concentrations of toxic elements were analyzed by ICP-MS. Results have shown
      that the level of natural radionuclides may not cause immediate or acute
      environmental impacts because the Raeq values and Hex (in the brick) are 345 Bq
      kg(-1) and 0.89, lower than the limit values of 370 Bq kg(-1) and 1,
      respectively. However, the Raeq and Hex values are near the limit values, their
      chronic-environmental and health impacts should be considered noteworthy. The
      elements found in the emission could be categorized into two types: non
      volatilized elements (Co, Cr, Mn and V) and volatilized elements (As, Cd, Cu, Ni,
      Se, Sn and Zn). Understanding the behaviors of natural radionuclides and toxic
      elements during brick making processes is helpful for the assessment of their
      potential impacts to human health and the environment.

PMID- 24103438
TI  - Food utilization and growth of cutworm Spodoptera litura Fabricius larvae exposed
      to nickel, and its effect on reproductive potential.
AB  - Food utilization and growth of the 5th and 6th instar Spodoptera litura Fabricius
      larvae, and its effect on reproduction potential was evaluated by feeding larvae
      diets with different doses of Ni for 3 generations. Dose-dependent relationships
      between Ni levels and food consumption and growth were variable with different
      larval developmental period and Ni exposure duration. RCR, AD and RGR of the 6th
      instar larvae were much more affected by Ni exposure than those of 5th instar
      larvae, and the effects were strongest in the 3rd generation. It was found that
      RCR was significantly stimulated after 1 and 20 mg kg(-1) Ni exposure, while AD
      was significantly inhibited after 1, 5, 10 and 40 mg kg(-1) Ni exposure. However,
      lower levels of Ni (<=5 mg kg(-1)) significantly increased and higher levels of
      Ni (>=10 mg kg(-1)) significantly decreased RGR. In 3 successive generations, 10
      mg kg(-1) Ni significantly increased the ECI and ECD of the 5th instar larvae,
      and 5 mg kg(-1) Ni significantly increased the ECD of the 6th instar larvae.
      However, ECD were all significantly inhibited with 20 mg kg(-1) Ni exposure.
      Results also revealed that durations of larvae were shortened at low levels of
      Ni, but extended at high levels of Ni. Fecundity was inhibited by the highest Ni
      doses in each generation, while improved by low Ni doses in the 3rd generation.
      Hatching rates in all treatments were significantly decreased in a Ni dose
      dependent manner. Study indicated that effects of Ni on these parameters were
      predominant with the increasing Ni exposure period.

PMID- 24103439
TI  - Production of a monoclonal antibody and development of an immunoassay for
      detection of Cr(III) in water samples.
AB  - In this study we report the production of a monoclonal antibody (Mab) specific
      for Cr(III)-chelate and the development of a competitive immunoassay for
      detection of Cr(III) in water samples. In the assay, the complete antigen
      (Cr(III)-ITCBE-BSA) was used as coating antigen, and Cr(III)-ITCBE as competitor
      competes with coating antigen to bind with Mab. Using this approach, the spiked
      water samples with Cr(III) were detected. The linear range of the detection was
      0.7-12.4 ng mL(-1). The limit of the detection (LOD) was 0.51 ng mL(-1). The
      spiked results were also confirmed by ICP-MS, which showed a good correlation
      (R(2)=0.997) between the two methods. The results indicated that the developed
      assay was reliable and suitable for the detection of Cr(III) in water samples.

PMID- 24103440
TI  - Organochlorine pesticides (OCPs) and polychlorinated biphenyls (PCBs) in
      sediments from the Gulf of Batabano, Cuba.
AB  - The spatial distribution of various organochlorinated compounds, e.g. PCBs, DDTs,
      HCB and HCHs, were investigated in sediments of the Gulf of Batabano, Cuba. Among
      the target organochlorine compounds measured, SigmaDDT isomers were the
      predominant contaminant with concentrations ranging from 0.019 to 1.27 ng g(
      1)dry wt. Lindane was present at very low concentrations in the range n.d. to
      0.05 ng g(-1), while PCBs and other organochlorine pesticide residues, such as
      HCB, Heptaclor, Aldrin and Mirex were lower than detection limits (~0.010 ng g(
      1)). According to established sediment quality guidelines, the OCPs
      concentrations encountered in the surface sediments are probably not having an
      adverse effect on sediment dwelling organisms. Compared to concentrations
      reported in coastal environments from other parts of the world, PCBs and OCs
      concentrations in surface sediments of Batabano Gulf were low and similar to the
      reported for remote and pristine environments. These results contribute to the
      sparse regional database for organochlorinated compounds in the Caribbean marine
      environment.

PMID- 24103442
TI  - Release of phosphorus under reducing and simulated open drainage conditions from
      overfertilised soils.
AB  - Does removal of cations from soil solution during soil reduction stimulate
      phosphorus (P) release? An ion-exchange resin system was employed to provide a
      sink during the incubation of twelve soils under fully reducing conditions. This
      experimental design was considered to better simulate the loss of ions likely to
      occur under field conditions than more routine batch type closed extraction
      systems where solutes build-up in the extract solution. The small solute
      concentrations that remain in the equilibrating solution suggest the mixed resin
      system acted as an effective sink over the whole experimental period. By
      maintaining a small P concentration the resin system mimics soil drainage
      conditions and encourages P release from soil. Measurement of soil P forms by
      sequential extraction after the incubation period indicated an increase in the
      amorphous forms present. Here we show that even if the P-containing solution is
      retained by the soil, the potential for a subsequent P loss is increased under
      aerobic conditions. The management of drainage systems should try and avoid the
      onset of anaerobic conditions. Eventually, magnesium- and calcium-based
      precipitation products could recapture P from drains recycling it in topsoils as
      fertilizer. 

PMID- 24103441
TI  - Evaluation of the potential of benchmarking to facilitate the measurement of
      chemical persistence in lakes.
AB  - The persistence of chemicals in the environment is rarely measured in the field
      due to a paucity of suitable methods. Here we explore the potential of chemical
      benchmarking to facilitate the measurement of persistence in lake systems using a
      multimedia chemical fate model. The model results show that persistence in a lake
      can be assessed by quantifying the ratio of test chemical and benchmark chemical
      at as few as two locations: the point of emission and the outlet of the lake.
      Appropriate selection of benchmark chemicals also allows pseudo-first-order rate
      constants for physical removal processes such as volatilization and sediment
      burial to be quantified. We use the model to explore how the maximum persistence
      that can be measured in a particular lake depends on the partitioning properties
      of the test chemical of interest and the characteristics of the lake. Our model
      experiments demonstrate that combining benchmarking techniques with good
      experimental design and sensitive environmental analytical chemistry may open new
      opportunities for quantifying chemical persistence, particularly for relatively
      slowly degradable chemicals for which current methods do not perform well. 

PMID- 24103443
TI  - Free air, but where?

PMID- 24103445
TI  - Nobel prize is awarded for studies of intracellular transport mechanisms.

PMID- 24103444
TI  - Specialist geriatric medical assessment for patients discharged from hospital
      acute assessment units: randomised controlled trial.
AB  - OBJECTIVE: To evaluate the effect of specialist geriatric medical management on
      the outcomes of at risk older people discharged from acute medical assessment
      units. DESIGN: Individual patient randomised controlled trial comparing
      intervention with usual care. SETTING: Two hospitals in Nottingham and Leicester,
      UK. PARTICIPANTS: 433 patients aged 70 or over who were discharged within 72
      hours of attending an acute medical assessment unit and at risk of decline as
      indicated by a score of at least 2 on the Identification of Seniors At Risk tool.
      INTERVENTION: Assessment made on the acute medical assessment unit and further
      outpatient management by specialist physicians in geriatric medicine, including
      advice and support to primary care services. MAIN OUTCOME MEASURES: The primary
      outcome was the number of days spent at home (for those admitted from home) or
      days spent in the same care home (if admitted from a care home) in the 90 days
      after randomisation. Secondary outcomes were determined at 90 days and included
      mortality, institutionalisation, dependency, mental wellbeing, quality of life,
      and health and social care resource use. RESULTS: The two groups were well
      matched for baseline characteristics, and withdrawal rates were similar in both
      groups (5%). Mean days at home over 90 days' follow-up were 80.2 days in the
      control group and 79.7 in the intervention group. The 95% confidence interval for
      the difference in means was -4.6 to 3.6 days (P=0.31). No significant differences
      were found for any of the secondary outcomes. CONCLUSIONS: This specialist
      geriatric medical intervention applied to an at risk population of older people
      attending and being discharged from acute medical units had no effect on
      patients' outcomes or subsequent use of secondary care or long term care.

PMID- 24103446
TI  - Guides on commissioning 28 surgical procedures aim to end postcode lottery.

PMID- 24103447
TI  - Distribution of erythrocyte binding antigen 175 (EBA-175) gene dimorphic alleles
      in Plasmodium falciparum field isolates from Sudan.
AB  - BACKGROUND: The Erythrocyte Binding Antigen (EBA) 175 has been considered as one
      of the most important Plasmodium falciparum (P. falciparum) merozoite ligands
      that mediate invasion of the erythrocytes through their sialated receptor:
      Glycophorin A (GPA). The effect of the EBA 175 dimorphic alleles (F and C) on the
      severity of the disease is not yet fully understood. Therefore this study was
      designed to assess the distribution of the divergent dimorphic alleles of P.
      falciparum EBA-175 (F and C) in three different geographical areas in Sudan and
      the possible association of this dimorphism with the severity of the disease.
      METHODS: A sum of 339 field isolates of P. falciparum obtained from patients in
      three different geographical areas in Sudan were screened for the dimorphic
      alleles (F, C) of the EBA-175 using nested PCR. RESULTS: The percentage of F, C,
      and mixed F/C alleles were; 41%, 51%, and 8% respectively. F and C alleles showed
      significantly different distributions in the various geographic areas (p = 0.00).
      There was no significant association between malaria clinical manifestation and
      P. falciparum EBA-175 F and C alleles frequencies. CONCLUSIONS: This study showed
      a significant differential distribution of F and C alleles in different
      geographical malaria endemic areas. No significant association was observed
      between F and C alleles and different malaria phenotypes.

PMID- 24103448
TI  - What is learned during simultaneous temporal acquisition? An individual-trials
      analysis.
AB  - The processes involved in the acquisition of simultaneous temporal processing are
      currently less understood. For example, it is unclear whether scalar property
      emerges early during simultaneous temporal acquisition. Using an information
      processing model which accounts for the amount of information that each temporal
      process provides in regard to reward time, we predicted that scalar property
      would emerge early during the acquisition process, but that subjects should take
      about 27% longer (more trials) to acquire the long duration than the short
      duration. To evaluate these predictions, we performed individual-trials analyses
      to identify changes in timing behavior when rats simultaneously acquire two
      criterion durations, either 10s and 20s (group 10/20) or 20s and 40s (group
      20/40). To analyze the individual trials we used a change-point algorithm to
      identify changes in rats' wait time. For each individual rat, and for each
      criterion duration, analyses indicated that simultaneous temporal acquisition is
      characterized by a sudden change in waiting to a wait-time proportional to the
      associated criterion. The results failed to indicate group differences in regard
      to the number of trials it takes for the change in wait-time to occur, but that
      in both groups, it took longer (more trials) to acquire the long duration than
      the shorter one, not significantly different from the theoretical prediction.
      These results are discussed in the framework of an information-processing model
      informing both associative and temporal learning, thus providing a bridge between
      the two fields. This article is part of a Special Issue entitled: Associative and
      Temporal Learning. 

PMID- 24103450
TI  - 'The charmingest place': non-coding RNA, lineage tracing, tumor heterogeneity,
      metastasis and metabolism--new methods in mammary gland development and cancer:
      the fifth ENBDC Workshop.
AB  - The European Network for Breast Development and Cancer (ENBDC) Workshop on
      'Methods in Mammary Gland Development and Cancer' has grown into the essential,
      international technical discussion forum for scientists with interests in the
      normal and neoplastic breast. The fifth ENBDC meeting was held in Weggis,
      Switzerland in April, 2013, and focussed on emerging, state-of-the-art techniques
      for the study of non-coding RNA, lineage tracing, tumor heterogeneity, metastasis
      and metabolism.

PMID- 24103449
TI  - Ozone induces glucose intolerance and systemic metabolic effects in young and
      aged Brown Norway rats.
AB  - Air pollutants have been associated with increased diabetes in humans. We
      hypothesized that ozone would impair glucose homeostasis by altering insulin
      signaling and/or endoplasmic reticular (ER) stress in young and aged rats. One,
      4, 12, and 24 month old Brown Norway (BN) rats were exposed to air or ozone, 0.25
      or 1.0 ppm, 6 h/day for 2 days (acute) or 2 d/week for 13 weeks (subchronic).
      Additionally, 4 month old rats were exposed to air or 1.0 ppm ozone, 6 h/day for
      1 or 2 days (time-course). Glucose tolerance tests (GTT) were performed
      immediately after exposure. Serum and tissue biomarkers were analyzed 18 h after
      final ozone for acute and subchronic studies, and immediately after each day of
      exposure in the time-course study. Age-related glucose intolerance and increases
      in metabolic biomarkers were apparent at baseline. Acute ozone caused
      hyperglycemia and glucose intolerance in rats of all ages. Ozone-induced glucose
      intolerance was reduced in rats exposed for 13 weeks. Acute, but not subchronic
      ozone increased alpha2-macroglobulin, adiponectin and osteopontin. Time-course
      analysis indicated glucose intolerance at days 1 and 2 (2>1), and a recovery 18 h
      post ozone. Leptin increased day 1 and epinephrine at all times after ozone.
      Ozone tended to decrease phosphorylated insulin receptor substrate-1 in liver and
      adipose tissues. ER stress appeared to be the consequence of ozone induced acute
      metabolic impairment since transcriptional markers of ER stress increased only
      after 2 days of ozone. In conclusion, acute ozone exposure induces marked
      systemic metabolic impairments in BN rats of all ages, likely through sympathetic
      stimulation.

PMID- 24103451
TI  - A minimally invasive sinus tarsi approach with percutaneous plate and screw
      fixation for intra-articular calcaneal fractures.
AB  - According to characteristic of anatomical structure of calcaneus and sinus tarsi
      approach, the minimally invasive plate for treatment of displaced intra-articular
      calcaneal fractures had been designed. Here we aimed to review the effect of this
      treatment. Forty intra-articular calcaneal fractures in 38 patients from
      September 2006 to September 2008 were treated with percutaneous plate via sinus
      tarsi approach under the monitoring of C-shaped arms. All calcaneal anatomical
      parameters, including height, width, length, Bohlers angle and Gissane angle were
      measured by X-ray before and after surgery. Postoperative lateral wound healing
      was also evaluated and clinical functional outcomes were graded using the
      Maryland foot score. All patients had been followed up for an average of 12
      months ranged from 3 months to 24 months. X-ray indicated satisfactory
      restoration of the calcaneal height, width, length, Bohlers angle and Gissanes
      angle. Maryland foot score demonstrated that excellent result was achieved in 32
      cases, good in 6 cases, fair in 2 cases, and the excellent and good rate was 95%.
      Postoperative complications were not found in all fractured feet. Our results
      suggest that this minimally invasive sinus tarsi approach with new designed plate
      and screw fixation technique for the treatment of intra-articular calcaneal
      fractures can not only obtain the satisfactory outcomes, but also can effectively
      prevent surgical complications. 

PMID- 24103452
TI  - Phenol-Explorer 3.0: a major update of the Phenol-Explorer database to
      incorporate data on the effects of food processing on polyphenol content.
AB  - Polyphenols are a major class of bioactive phytochemicals whose consumption may
      play a role in the prevention of a number of chronic diseases such as
      cardiovascular diseases, type II diabetes and cancers. Phenol-Explorer, launched
      in 2009, is the only freely available web-based database on the content of
      polyphenols in food and their in vivo metabolism and pharmacokinetics. Here we
      report the third release of the database (Phenol-Explorer 3.0), which adds data
      on the effects of food processing on polyphenol contents in foods. Data on >100
      foods, covering 161 polyphenols or groups of polyphenols before and after
      processing, were collected from 129 peer-reviewed publications and entered into
      new tables linked to the existing relational design. The effect of processing on
      polyphenol content is expressed in the form of retention factor coefficients, or
      the proportion of a given polyphenol retained after processing, adjusted for
      change in water content. The result is the first database on the effects of food
      processing on polyphenol content and, following the model initially defined for
      Phenol-Explorer, all data may be traced back to original sources. The new update
      will allow polyphenol scientists to more accurately estimate polyphenol exposure
      from dietary surveys.

PMID- 24103453
TI  - Achromatic luminance contrast sensitivity in X-linked color-deficient observers:
      an addition to the debate.
AB  - It is a matter of debate whether X-linked dichromacy is accompanied by enhanced
      achromatic processing. In the present study, we used sinusoidally modulated
      achromatic gratings under photopic conditions to compare the contrast sensitivity
      (CS) of protanopes, deuteranopes, and normal trichromats. 36 male volunteers were
      examined. CS was tested in static and dynamic conditions at nine different
      spatial frequencies. The results support the assumption that X-linked color
      defective observers are at an advantage in terms of achromatic processing. Both
      protanopes and deuteranopes had significantly better CS than controls in both the
      static and the dynamic conditions. In the static condition, the advantage was
      observed especially at higher spatial frequencies, whereas in the dynamic
      condition, it was seen also at lower frequencies. The results are interpreted in
      terms of decreased chromatic modulation of the luminance channel and the early
      plasticity of the parvocellular system. 

PMID- 24103454
TI  - MiR-23a-mediated inhibition of topoisomerase 1 expression potentiates cell
      response to etoposide in human hepatocellular carcinoma.
AB  - BACKGROUND: microRNAs have been shown to regulate the chemosensitivity of cancer
      cells. The aim of this study is to investigate the role and mechanism of mir-23a
      in enhancing the anti-tumor effect of topoisomerase 2A (TOP2A) poison etoposide
      in human hepatocellular carcinoma (HCC). METHODS: The anti-tumor effect of
      chemotherapeutic agents in HCC cells were examined in vitro and in vivo xenograft
      model. Expression of mRNA and miRNAs were determined by quantitative real-time
      PCR. Protein expression was analyzed by immunoblotting. RESULTS: Overexpression
      of mir-23a could significantly potentiate the in vitro and in vivo anti-tumor
      effect of etoposide; however, ectopic expression of miR-23a fails to sensitize
      HCC cells to 5-fluorouracil treatment, indicating the miR-23a-induced cancer cell
      hypersensitivity in chemotherapy is TOP2A-specific though miR-23a overexpression
      could not directly up-regulate TOP2A expression. Topoisomerase 1(TOP1) is down
      regulated in miR-23a-overexpressed HCC cells. MiR-23a could directly bind to
      3'untranslated region of TOP1 mRNA, and suppress the corresponding protein
      expression and inhibition of miR-23a further arguments the expression of TOP1.
      MiR-23a was up-regulated during DNA damage in cancer cells in line with the p53
      expression. Up-regulation of p53 induces mir-23a expression, while suppression of
      p53 inhibits miR-23a in HCC cells. CONCLUSION: Our study sheds light on the role
      of miR-23a as a potential target in regulating chemosensitivity of HCC cells.

PMID- 24103455
TI  - Body mass index and overweight in relation to residence distance and population
      density: experience from the Northern Finland birth cohort 1966.
AB  - BACKGROUND: The effect of urban sprawl on body weight in Finland is not well
      known. To provide more information, we examined whether body mass index (BMI) and
      the prevalence of overweight are associated with an individual's distance to the
      local community centre and population density in his/her resident area. METHODS:
      The sample consisted of 5363 men and women, members of the Northern Finland Birth
      Cohort 1966 (NFBC), who filled in a postal questionnaire and attended a medical
      checkup in 1997, at the age of 31 years. Body mass index (BMI; kg/m(2)) and the
      prevalence of overweight (BMI >= 25.0 kg/m(2)) were regressed on each subject's
      road distance to the resident commune's centre and on population density in the 1
      km(2) geographical grid in which he/she resided, using a generalized additive
      model. Adjustments were made for sex, marital status, occupational class,
      education, leisure-time and occupational physical activity, alcohol consumption
      and smoking. RESULTS: The mean BMI among the subjects was 24.7 kg/m(2), but it
      increased by increasing road distance (by 1.3 kg/m(2) from 5-10 to 20-184 km) and
      by decreasing population density (by 1.7 kg/m(2) from 1000-19,192 to 1-5
      inhabitants/km(2)). The respective increases in overweight (overall prevalence
      41%) were 13 per cent units for distance and 14 per cent units for population
      density. Adjusted regressions based on continuous explanatory variables showed an
      inverse L-shaped pattern with a mean BMI of 24.6 kg/m(2) at distances shorter
      than 5 km and a rise of 2.6 kg/m(2) at longer distances, and an increase of 2.5
      kg/m(2) from highest to lowest population density. The associations with road
      distance were stronger for women than men, while the sex difference in
      association with population density remained indeterminate. CONCLUSIONS: We
      conclude that young adults in Northern Finland who live far away from local
      centres or in the most sparsely populated areas are fatter than those who live
      close to local centres or in densely populated areas. The likely explanations
      include variations in everyday physical activity in different residential
      environments, although causality of the associations remains to be confirmed.

PMID- 24103456
TI  - Pneumocephalus in pneumococcal meningitis.

PMID- 24103457
TI  - Impact of fibrinogen concentrate alone or with prothrombin complex concentrate
      (+/- fresh frozen plasma) on plasma fibrinogen level and fibrin-based clot
      strength (FIBTEM) in major trauma: a retrospective study.
AB  - BACKGROUND: Low plasma fibrinogen concentration is a predictor of poor outcome in
      major trauma patients. The role of fibrinogen concentrate for rapidly increasing
      fibrinogen plasma levels in severe trauma is not well defined. METHODS: In this
      retrospective study we included severe trauma patients treated with fibrinogen
      concentrate alone (FC group), fibrinogen concentrate with prothrombin complex
      concentrate (FC-PCC group) or fibrinogen concentrate with PCC and fresh frozen
      plasma (FC-PCC-FFP group). PCC was generally administered as the second step of
      intraoperative therapy, while FFP was only administered as a third step. All
      patients received >=1 g fibrinogen concentrate within 24 hours. Plasma fibrinogen
      concentration and ROTEM parameters upon emergency room (ER) admission, intensive
      care unit (ICU) admission, and after 24 hours were analysed. RESULTS: Among 157
      patients fulfilling the inclusion criteria, 83% were male; mean age was 44 years
      and median injury severity score (ISS) was 29. Standard coagulation tests
      reflected increasing severity of coagulopathy with increasing complexity of
      haemostatic therapy (highest severity in the FC-PCC-FFP group; p < 0.0001). Total
      24-hour fibrinogen concentrate dose also increased with complexity of haemostatic
      therapy. Plasma fibrinogen concentration was maintained, with no significant
      difference between ER admission and ICU admission in all patient groups. FIBTEM
      clot firmness at 10 minutes (CA10) was similarly maintained, albeit with a small
      increase in the FC-PCC group. Fibrinogen concentration and FIBTEM CA10 were
      within the normal range in all groups at 24 hours. The ratio of fibrinogen
      concentrate to red blood cells (g:U) ranged between 0.7:1.0 and 1.0:1.0.
      CONCLUSION: Fibrinogen concentrate therapy maintained fibrinogen concentration
      and FIBTEM CA10 during the initial phase of trauma care until ICU admission.
      After 24 hours, these parameters were comparable between the three groups and
      within the normal range for each of them. Further studies are warranted to
      investigate the effect of fibrinogen concentrate on clinical outcomes.

PMID- 24103458
TI  - Characteristics of fast-food/takeaway-food and restaurant/cafe-food consumers
      among New Zealand adults.
AB  - OBJECTIVE: To investigate: (i) the percentage of the New Zealand (NZ) population
      reporting fast food/takeaway food and restaurant/cafe food per day; (ii) examine
      demographic factors associated with their use; (iii) quantify their contribution
      to energy intake; and (iv) describe the specific types of foods reported from
      both sources. DESIGN: Twenty-four hour diet recalls from the cross-sectional
      2008/09 NZ Adult Nutrition Survey were used to identify fast-food and restaurant
      food consumers. SETTING: NZ households. SUBJECTS: Adults aged 15 years and older
      (n 4721). RESULTS: Overall 28 % reported consuming at least one fast food and 14
      % a restaurant food within the 24 h diet recall. Fast-food consumption was not
      associated with level of education or an area-based measure of socio-economic
      status, but a higher education was positively associated with restaurant-food
      consumption. Individual factors such as ethnicity, household size, age, sex and
      marital status were found to be important influences on the use of fast food and
      restaurant food. Fast-food consumption was more prevalent among participants
      living in urban areas, young adults (19-30 years) and Maori compared with NZ
      European and Others. The most frequently reported fast foods were bread-based
      dishes, potatoes (including fries) and non-alcoholic beverages. CONCLUSIONS:
      Given the high reported consumption of fast food by young adults, health
      promotion initiatives both to improve the nutritional quality of fast-food menus
      and to encourage healthier food choices would likely make a large impact on the
      overall diet quality of this group.

PMID- 24103459
TI  - Circulation of whale-bone artifacts in the northern Pyrenees during the late
      Upper Paleolithic.
AB  - The importance of coastal resources in the late Upper Paleolithic of western
      Europe has been reevaluated in recent years thanks to a growing body of new
      archeological evidence, including the identification of more than 50 implements
      made of whale bone in the Magdalenian level of the Isturitz cave (western
      Pyrenees). In the present study, the assemblages of osseous industry from 23
      Magdalenian sites and site clusters in the northern Pyrenees were investigated,
      systematically searching for whale-bone implements. The objective of this
      research was to determine if, and how, tools and weapons of coastal origin were
      circulated beyond Isturitz into the inland, and if similar implements existed on
      the eastern, Mediterranean side of the Pyrenees. A total of 109 whale-bone
      artifacts, mostly projectile heads of large dimensions, were identified in 11
      sites. Their geographic distribution shows that whale bone in the Pyrenean
      Magdalenian is exclusively of Atlantic origin, and that objects made of this
      material were transported along the Pyrenees up to the central part of the range
      at travel distances of at least 350 km from the seashore. This phenomenon seems
      to have taken place during the second half of the Middle Magdalenian and the
      first half of the Late Magdalenian, ca. 17,500-15,000 cal BP (calibrated years
      before present). The existence of a durable, extended coastal-inland interaction
      network including the circulation of regular tools is thus demonstrated.
      Additionally, differences between the whale-bone projectile heads of the Middle
      Magdalenian and those of the Late Magdalenian document an evolutionary process in
      the design of hunting weapons. 

PMID- 24103460
TI  - Reply to Comments on neonatal hair-Hg and birth weight in China: mercury in rice
      and fish.

PMID- 24103461
TI  - Comparison of postoperative stability of three rigid internal fixation techniques
      after sagittal split ramus osteotomy for mandibular advancement.
AB  - INTRODUCTION: The aim of this investigation was to compare the skeletal stability
      of three different rigid fixation methods after mandibular advancement. MATERIAL
      AND METHODS: Fifty-five class II malocclusion patients treated with the use of
      bilateral sagittal split ramus osteotomy and mandibular advancement were selected
      for this retrospective study. Group 1 (n = 17) had miniplates with monocortical
      screws, Group 2 (n = 16) had bicortical screws and Group 3 (n = 22) had the
      osteotomy fixed by means of the hybrid technique. Cephalograms were taken
      preoperatively, 1 week within the postoperative care period, and 6 months after
      the orthognathic surgery. Linear and angular changes of the cephalometric
      landmarks of the chin region were measured at each period, and the changes at
      each cephalometric landmark were determined for the time gaps. Postoperative
      changes in the mandibular shape were analyzed to determine the stability of
      fixation methods. RESULTS: There was minimum difference in the relapse of the
      mandibular advancement among the three groups. Statistical analysis showed no
      significant difference in postoperative stability. However, a positive
      correlation between the amount of advancement and the amount of postoperative
      relapse was demonstrated by the linear multiple regression test (p < 0.05).
      CONCLUSION: It can be concluded that all techniques can be used to obtain stable
      postoperative results in mandibular advancement after 6 months.

PMID- 24103462
TI  - Is buccal fat pad a better option than nasolabial flap for reconstruction of
      intraoral defects after surgical release of fibrous bands in patients with oral
      submucous fibrosis? A pilot study: a protocol for the management of oral
      submucous fibrosis.
AB  - PURPOSE: The aim this study was to compare the buccal fat pad (BFP) and
      nasolabial flap for reconstruction of intraoral defects after release of fibrous
      bands in patients with oral submucous fibrosis (OSF). MATERIALS AND METHODS: This
      is a comparative study. The study sample was derived from the population of
      patients who presented, with restricted mouth opening of less than 20 mm, to the
      Department of Oral and Maxillofacial Surgery, Swargiya Dada Saheb Kalmegh Dental
      College and Hospital Hingna Nagpur. The patients were divided into two groups. In
      Group I (n = 10) reconstruction was performed with a nasolabial flap and in Group
      II (n = 10) with BFP. Both groups were analysed separately for mouth opening
      (interincisal distance in millimetres) preoperatively and 20 months
      postoperatively, time taken for epithelialization of BFP and nasolabial flaps.
      Statistical analysis was performed with SPSS statistical software for Windows,
      version 8.0 (SPSS, Inc, Chicago, IL) using the _2 test and Student's t test.
      RESULTS: In all 20 patients the interincisal mouth opening was (mean) 11 mm (3-19
      mm) preoperatively which improved to a mean of 42 mm (23-52 mm). In Group I there
      were more complications as compared to Group II such as partial flap necrosis
      particularly at the tips, temporary widening of oral commissure and subluxation
      of TMJ. The unsightly extraoral scar and intraoral growth of hairs were not seen
      in Group II. CONCLUSION: BFP is the better choice for reconstruction in
      comparison to nasolabial flap.

PMID- 24103463
TI  - Postoperative bleeding risk for cutaneous surgery in the head and neck region
      with continued phenprocoumon therapy.
AB  - In a total of 171 surgical procedures for lesions in the head and neck region in
      patients in whom phenprocoumon therapy was not stopped, 16 (9%) postoperative
      bleeding events were observed over a follow-up period of two weeks. Local
      measures were sufficient in all cases except one severe case where blood
      transfusion was needed and anticoagulant treatment was stopped for 7 days. The
      bleeding risk was significantly higher for the surgical procedures of the nose
      than those in other areas (21% versus 6%, P = 0.014), but was not influenced by
      the international normalized ratio (INR) of blood coagulation, size, site and
      type of the lesion, surgical procedure, and sex and age of the patients. The
      bleeding rate in patients not on any anticoagulation therapy was significantly
      lower (6/211 = 3%). Across both groups, just over 80% of the bleeding episodes
      were within the first two days (55% on the same day and 32% on the next day) of
      the surgery. No bleeding was recorded after 5 days. Our data suggest that
      cutaneous surgery in the head and neck region can be safely performed with
      continued phenprocoumon therapy in most cases in an INR range of 1.3-3.4, but
      rarely severe bleeding does occur and can be managed with a close-contact follow
      up and with 24-h on call services during the first two days postoperatively. 

PMID- 24103464
TI  - Synthesis, characterization and in vitro studies of celecoxib-loaded poly(ortho
      ester) nanoparticles targeted for intraocular drug delivery.
AB  - The present investigation is aimed at improving the ocular bioavailability of a
      poorly water soluble drug, celecoxib, to offer new options in the treatment of
      chronic eye diseases, such as age-related macular degeneration and diabetic
      retinopathy. To do so, we developed a novel formulation of drug-loaded poly(ortho
      ester) nanoparticles (NPs). We characterized the NPs in terms of size,
      morphology, controlled-release, degradation and cytocompatibity. Stable and
      transparent NP emulsions were prepared following a double emulsion solvent
      diffusion method employing poloxamer 188 as a stabilizer. Physical properties
      showed a narrow range size distribution of 151-164nm with spherical morphology,
      negative zeta potentials and remarkably high celecoxib encapsulation efficiency
      (98%) and loading (64%) of poly(ortho ester) NPs. Drug release followed a zero
      order release by a surface erosion-controlled mechanism without any burst effect.
      Degradation of poly(ortho ester) NPs was observed by measuring the concentration
      of initial degradation product such as, lactic acid. MTT studies revealed minimal
      toxicity of NPs (up to 1mg/ml) toward HEK 293 cells. Poly(ortho ester) NPs were
      not internalized by either Muller or HEK 293 cells, which is highly desirable for
      a drug carrier to deliver the drugs for prolonged periods to the back of eye.
      These features have the potential to decrease the number of intraocular
      injections required to treat chronic eye diseases. 

PMID- 24103465
TI  - Rare recessive loss-of-function methionyl-tRNA synthetase mutations presenting as
      a multi-organ phenotype.
AB  - BACKGROUND: Methionyl-tRNA synthetase (MARS) catalyzes the ligation of methionine
      to its cognate transfer RNA and therefore plays an essential role in protein
      biosynthesis. METHODS: We used exome sequencing, aminoacylation assays, homology
      modeling, and immuno-isolation of transfected MARS to identify and characterize
      mutations in the methionyl-tRNA synthetase gene (MARS) in an infant with an
      unexplained multi-organ phenotype. RESULTS: We identified compound heterozygous
      mutations (F370L and I523T) in highly conserved regions of MARS. The parents were
      each heterozygous for one of the mutations. Aminoacylation assays documented that
      the F370L and I523T MARS mutants had 18 +/- 6% and 16 +/- 6%, respectively, of
      wild-type activity. Homology modeling of the human MARS sequence with the
      structure of E. coli MARS showed that the F370L and I523T mutations are in close
      proximity to each other, with residue I523 located in the methionine binding
      pocket. We found that the F370L and I523T mutations did not affect the
      association of MARS with the multisynthetase complex. CONCLUSION: This infant
      expands the catalogue of inherited human diseases caused by mutations in
      aminoacyl-tRNA synthetase genes.

PMID- 24103466
TI  - Re-thinking resuscitation: leaving blood pressure cosmetics behind and moving
      forward to permissive hypotension and a tissue perfusion-based approach.
AB  - Definitions of shock and resuscitation endpoints traditionally focus on blood
      pressures and cardiac output. This carries a high risk of overemphasizing
      systemic hemodynamics at the cost of tissue perfusion. In line with novel shock
      definitions and evidence of the lack of a correlation between macro- and
      microcirculation in shock, we recommend that macrocirculatory resuscitation
      endpoints, particularly arterial and central venous pressure as well as cardiac
      output, be reconsidered. In this viewpoint article, we propose a three-step
      approach of resuscitation endpoints in shock of all origins. This approach
      targets only a minimum individual and context-sensitive mean arterial blood
      pressure (for example, 45 to 50 mm Hg) to preserve heart and brain perfusion.
      Further resuscitation is exclusively guided by endpoints of tissue perfusion
      irrespectively of the presence of arterial hypotension ('permissive
      hypotension'). Finally, optimization of individual tissue (for example, renal)
      perfusion is targeted. Prospective clinical studies are necessary to confirm the
      postulated benefits of targeting these resuscitation endpoints. 

PMID- 24103467
TI  - Label-free in vitro toxicity and uptake assessment of citrate stabilised gold
      nanoparticles in three cell lines.
AB  - BACKGROUND: Reliable in vitro toxicity testing is needed prior to the
      commencement of in vivo testing necessary for hazard identification and risk
      assessment of nanoparticles. In this study, the cytotoxicity and uptake of 14 nm
      and 20 nm citrate stabilised gold nanoparticles (AuNPs) in the bronchial
      epithelial cell line BEAS-2B, the Chinese hamster ovary cell line CHO, and the
      human embryonic kidney cell line HEK 293 were investigated. METHODS: Cytotoxicity
      of the AuNPs was assessed via traditional XTT-, LDH-, and ATP-based assays,
      followed by cell impedance studies. Dark-field imaging and hyperspectral imaging
      were used to confirm the uptake of AuNPs into the cells. RESULTS: Interference of
      the AuNPs with the XTT- and ATP-based assays was overcome through the use of cell
      impedance technology. AuNPs were shown to be relatively non-toxic using this
      methodology; nevertheless CHO cells were the most sensitive cell type with 20 nm
      AuNPs having the highest toxicity. Uptake of both 14 nm and 20 nm AuNPs was
      observed in all cell lines in a time- and cell type-dependent manner.
      CONCLUSIONS: Using the cell impedance and dark-field hyperspectral imaging
      technologies, it was possible to study the toxicity of AuNPs in different cell
      lines and show that these cells could internalize AuNPs with their subsequent
      intracellular aggregation. It was also possible to show that this toxicity would
      not correlate with the level of uptake but it would correlate with cell-type and
      the size of the AuNPs. Therefore, these two label-free methodologies used in this
      study are suitable for in vitro studies on the effects of AuNPs, and could
      present themselves as appropriate and valuable methodologies for future
      nanoparticle toxicity and uptake studies.

PMID- 24103469
TI  - Testing the effect of the epidemiologic paradox: birth weight of newborns of
      immigrant and non-immigrant mothers in the region of Valencia, Spain.
AB  - The epidemiological paradox and 'healthy migrant effect' refer to the favourable
      health outcomes in unprivileged groups under unfavourable socioeconomic
      conditions. Weight at birth is associated with the epidemiological paradox.
      However, differences in fertility structure (mainly mother's age and first
      maternity) might be the cause of the difference in weight at birth between
      children of immigrant and non-immigrant mothers. This paper aims to analyse the
      impact of the epidemiologic paradox by distinguishing between the factors related
      to fertility structure, in addition to other socio-cultural factors. The
      importance of fertility structure as the cause of weight-at-birth differences of
      the newborns of immigrant and non-immigrant women, and between those of subgroups
      of immigrant mothers, is tested. Based on data from birth registries for the
      period 1998-2009, a variance analysis was performed for Spanish mothers and for
      those of five major immigrant subgroups living in the region of Valencia, Spain,
      which experienced significant migrant inflows within a short period of time. A
      Scheffe test between pairs of nationalities was carried out. Finally, linear
      regression models were built. The results suggest that the most relevant factors
      are those related to fertility structure, and that consequently the
      epidemiological paradox does not apply for immigrant mothers as a whole, although
      Bolivian immigrant offspring may be an exception. This unexpected result requires
      further research to test to what extent this is due to the special adaptation of
      multigenerational high-altitude populations in pregnancy. The factors associated
      with fertility structure must be controlled when trying to relate birth weight
      differences between ethnic groups to socioeconomic factors.

PMID- 24103468
TI  - Special issue on IS/IT Applications for the Support of Older People.

PMID- 24103470
TI  - Cell-free unnatural amino acid incorporation with alternative energy systems and
      linear expression templates.
AB  - Site-specific incorporation of unnatural amino acids (uAAs) during protein
      synthesis expands the proteomic code through the addition of unique residue
      chemistry. This field provides a unique tool to improve pharmacokinetics, cancer
      treatments, vaccine development, proteomics and protein engineering. The limited
      ability to predict the characteristics of proteins with uAA-incorporation creates
      a need for a low-cost system with the potential for rapid screening. Escherichia
      coli-based cell-free protein synthesis is a compelling platform for uAA
      incorporation due to the open and accessible nature of the reaction environment.
      However, typical cell-free systems can be expensive due to the high cost of
      energizing reagents. By employing alternative energy sources, we reduce the cost
      of uAA-incorporation in CFPS by 55%. While alternative energy systems reduce
      cost, the time investment to develop gene libraries can remain cumbersome. Cell
      free systems allow the direct use of PCR products known as linear expression
      templates, thus alleviating tedious plasmid library preparations steps. We report
      the specific costs of CFPS with uAA incorporation, demonstrate that LETs are
      suitable expression templates with uAA-incorporation, and consider the
      substantial reduction in labor intensity using LET-based expression for CFPS uAA
      incorporation.

PMID- 24103471
TI  - Evaluation of the quality of the management of cancer of the corpus uteri-
      selection of relevant quality indicators and implementation in Belgium.
AB  - OBJECTIVE: Describe the methodology and selection of quality indicators (QI) to
      be implemented in the EFFECT (EFFectiveness of Endometrial Cancer Treatment)
      project. EFFECT aims to monitor the variability in Quality of Care (QoC) of
      uterine cancer in Belgium, to compare the effectiveness of different treatment
      strategies to improve the QoC and to check the internal validity of the QI to
      validate the impact of process indicators on outcome. METHODS: A QI list was
      retrieved from literature, recent guidelines and QI databases. The Belgian
      Healthcare Knowledge Center methodology was used for the selection process and
      involved an expert's panel rating the QI on 4 criteria. The resulting scores and
      further discussion resulted in a final QI list. An online EFFECT module was
      developed by the Belgian Cancer Registry including the list of variables required
      for measuring the QI. Three test phases were performed to evaluate the relevance,
      feasibility and understanding of the variables and to test the compatibility of
      the dataset. RESULTS: 138 QI were considered for further discussion and 82 QI
      were eligible for rating. Based on the rating scores and consensus among the
      expert's panel, 41 QI were considered measurable and relevant. Testing of the
      data collection enabled optimization of the content and the user-friendliness of
      the dataset and online module. CONCLUSIONS: This first Belgian initiative for
      monitoring the QoC of uterine cancer indicates that the previously used QI
      selection methodology is reproducible for uterine cancer. The QI list could be
      applied by other research groups for comparison.

PMID- 24103472
TI  - Effect of the Go4it multidisciplinary group treatment for obese adolescents on
      health related quality of life: a randomised controlled trial.
AB  - BACKGROUND: We developed a Dutch outpatient multidisciplinary group treatment
      (Go4it) for obese adolescents, including cognitive behavioural therapy and
      education on healthy dietary and physical activity behaviour. This study examined
      the effect of Go4it on Health Related Quality of Life (HRQoL). METHODS: At our
      outpatient paediatric obesity clinic, obese adolescents (n = 122, 11-18 years)
      were randomly assigned to 1) Go4it, 7 sessions with an interval of 2 weeks or 2)
      current regular care consisting of referral to a dietician in the home care
      setting (controls). Linear mixed model analysis was performed to evaluate the
      intervention effects on HRQoL at 6 and 18-month follow-ups. HRQoL indicators
      included the Child Health Questionnaire, the Paediatric Quality of Life
      InventoryTM Version 4.0 (PedsQLTM4.0), and the Body Esteem Scale (BES). RESULTS:
      In total, 95 adolescents (Go4it 57, controls 38) were included in the current
      analysis with a mean age of 14.5 +/- 1.7 and mean BMI-SDS of 2.9 +/- 0.5. At
      baseline, all participants experienced lower levels of physical and psychosocial
      well-being compared to a normal weight reference group. At the 18 month follow
      up, we found small but beneficial intervention effects on all subscales of the
      PedsQLTM4.0 and BES questionnaires. Two subscales improved significantly; i.e.,
      physical health (between group difference 5.4; 95%CI: 0.3; 10.6), and school
      functioning (between group difference 7.4; 95%CI: 1.6; 13.2). CONCLUSION: Obese
      adolescents experienced lower HRQoL than their healthy peers. The Go4it
      intervention had small beneficial effects on HRQoL compared to the current
      regular care practices for obese adolescents. TRIAL REGISTRATION: Netherlands
      Trial Register: ISRCTN27626398, METC number: 05.134 (WMO, monocenter).

PMID- 24103474
TI  - Neuropathic pain as a result of acromegaly, treated with topical baclofen cream.

PMID- 24103475
TI  - From the battlefield to the palliative care arsenal: application of QuickClot
      Combat Gauze for aggressive palliation of hemorrhagic shock in the setting of end
      stage liver disease-associated compartment syndrome.

PMID- 24103476
TI  - Die in a foreign land or forgo cancer care: difficult choices faced by the
      expatriate workers in the United Arab Emirates.

PMID- 24103477
TI  - Methylenetetrahydrofolate reductase C677T and methionine synthase A2756G
      polymorphisms influence on leukocyte genomic DNA methylation level.
AB  - Methionine synthase (MTR) and methylenetetrahydrofolate reductase (MTHFR) enzymes
      are involved in the metabolism of methyl groups, and thus have an important role
      in the maintenance of proper DNA methylation level. In our study we aimed to
      evaluate the effect of the polymorphism A2756G (rs1805087) in the MTR gene on the
      level of human leukocyte genomic DNA methylation. Since the well-studied
      polymorphism C677T (rs1801133) in the MTHFR gene has already been shown to affect
      DNA methylation, we aimed to analyze the effect of MTR A2756G independently of
      the MTHFR C677T polymorphism. For this purpose, we collected the groups of 80
      subjects with the MTR 2756AA genotype and 80 subjects with the MTR 2756GG
      genotype, having equal numbers of individuals with the MTHFR 677CC and the MTHFR
      677TT genotypes, and determined the level of DNA methylation in each group.
      Individuals homozygous for the mutant MTR 2756G allele showed higher DNA
      methylation level than those harboring the MTR 2756AA genotype (5.061 +/- 1.761%
      vs. 4.501 +/- 1.621%, P=0.0391). Individuals with wild-type MTHFR 677SC genotype
      displayed higher DNA methylation level than the subjects with mutant MTHFR 677TT
      genotype (5.103 +/- 1.767% vs. 4.323 +/- 1.525%, P=0.0034). Our data provide
      evidence that the MTR A2756G polymorphism increases the level of DNA methylation
      and confirm the previous reports that the MTHFR C677T polymorphism is associated
      with DNA hypomethylation.

PMID- 24103478
TI  - Contribution of PTPN22, CD28, CTLA-4 and ZAP-70 variants to the risk of type 1
      diabetes in Tunisians.
AB  - Type 1 diabetes (T1D) is caused by an immune-mediated destruction of the insulin
      producing beta-cells. Several studies support the involvement of T cell
      activation molecules. In order to underline the role of the genes involved in
      this pathway, we investigated, using the Sequenom MassARRAY platform,
      polymorphisms of sixteen single-nucleotide polymorphisms (SNPs) belonging to
      PTPN22, CD28, CTLA-4, and ZAP-70 genes in 76 T1D patients and 162 unrelated
      healthy controls from Southern Tunisia. We confirmed the association with PTPN22
      (rs2476601, Corrected P (Pcorr)=0.002, OR=6.20) and CD28 gene (rs1879877,
      Pcorr=0.003; OR=4.27 and rs3181096, Pcorr=0.02; OR=1.73). We also identified an
      association with rs17695937 of ZAP-70 gene (Pcorr=0.02, OR=1.87). Our results
      suggest a significant effect on T1D susceptibility for A-C-A-G-C and T-C-C-T-A-C
      haplotypes, of ZAP-70 and CD28 genes, respectively. In addition, (A-G-C)
      combination of ZAP-70/CD28 gene was significantly increased in T1D patients as
      compared to controls, suggesting the possible interaction between these genes.
      These results confirm the involvement of PTPN22 and CD28 genes in the genetic
      susceptibility to T1D. Interestingly, ZAP-70 seems to contribute to the
      susceptibility to the disease in our population. However, this finding has to be
      confirmed in further studies.

PMID- 24103479
TI  - Variable expression of lineage regulators in differentiated stromal cells
      indicates distinct mechanisms of differentiation towards common cell fate.
AB  - Mesenchymal stem cells (MSCs) possess a multi-lineage differentiation capacity
      that makes them important players in the field of regenerative medicine. MSC
      populations derived from different tissues or donors have been shown to exhibit
      variable gene expression patterns. Further, it is widely acknowledged that MSC
      isolates are heterogeneous mixtures of cells at different developmental stages.
      However, the heterogeneity of expression of lineage regulators has not been
      linked to differentiation potential of different MSC populations towards
      mesenchymal lineages. Here, we analyzed variation of expression of
      differentiation markers across whole population and between single
      differentiating cells of multipotent stromal cell populations derived from
      adipose tissue (AdMSCs) and skin (FBs) of seven donors. The results of the
      analyses show that all cell populations exhibit similar differentiation potential
      towards adipocyte, osteoblast and chondrocyte lineages despite tissue type- and
      donor-specific variations of expression of differentiation-associated genes.
      Further, we detected variable expression of lineage regulators in individual
      differentiating cells. Together, our data indicate that single cells of stromal
      cell populations could use distinct molecular mechanisms to reach a common cell
      fate. 

PMID- 24103480
TI  - Novel complex re-arrangement of ARG1 commonly shared by unrelated patients with
      hyperargininemia.
AB  - BACKGROUND: Hyperargininemia is a very rare progressive neurometabolic disorder
      caused by deficiency of hepatic cytosolic arginase I, resulting from mutations in
      the ARG1 gene. Until now, some mutations were reported worldwide and none of them
      were of Southeast Asian origins. Furthermore, most reported mutations were point
      mutations and a few others deletions or insertions. OBJECTIVE: This study aims at
      identifying the disease-causing mutation in the ARG1 gene of Malaysian patients
      with hyperargininemia. METHODOLOGY: We employed a series of PCR amplifications
      and direct sequencing in order to identify the mutation. We subsequently used
      quantitative real-time PCR to determine the copy number of the exons flanking the
      mutation. We blasted our sequencing data with that of the reference sequence in
      the NCBI in order to obtain positional insights of the mutation. RESULTS: We
      found a novel complex re-arrangement involving insertion, inversion and gross
      deletion of ARG1 (designated
      g.insIVS1+1899GTTTTATCAT;g.invIVS1+1933_+1953;g.delIVS1+1954_IVS2+914;c.del116_18
      ;p.Pro20SerfsX4) commonly shared by 5 patients with hyperargininemia, each
      originating from different family. None of the affected families share known
      relationship with each other, although four of the five patients were known to
      have first-cousin consanguineous parents. CONCLUSION: This is the first report of
      complex re-arrangement in the ARG1. Further analyses showing that the patients
      have shared the same geographic origin within the northeastern part of Malaysia
      prompted us to suggest a simple molecular screening of hyperargininemia within
      related ethnicities using a long-range PCR.

PMID- 24103481
TI  - A novel mutation in PLP1 causes severe hereditary spastic paraplegia type 2.
AB  - Hereditary spastic paraplegia (HSP) type 2 is a proteolipid protein (PLP1)
      related genetic disorder that is characterized by dysmyelination of the central
      nervous system resulting primarily in limb spasticity, cognitive impairment,
      nystagmus, and spastic urinary bladder of varying severity. Previously reported
      PLP1 mutations include duplications, point mutations, or whole gene deletions
      with a continuum of phenotypes ranging from severe Pelizaeus-Merzbacher disease
      (PMD) to uncomplicated HSP type 2. In this manuscript we report a novel PLP1
      missense mutation (c.88G>C) in a family from Argentina. This mutation is in a
      highly conserved transmembrane domain of PLP1 and the mutant protein was found to
      be retained in the endoplasmic reticulum when expressed in vitro. Due to the
      variable expressivity that characterizes these disorders our report contributes
      to the knowledge of genotype-phenotype correlations of PLP1-related disorders. 

PMID- 24103482
TI  - Legumes and meat analogues consumption are associated with hip fracture risk
      independently of meat intake among Caucasian men and women: the Adventist Health
      Study-2.
AB  - OBJECTIVE: In contrast to non-vegetarians, vegetarians consume more legumes and
      meat analogues as sources of protein to substitute for meat intake. The present
      study aimed to assess the association between foods with high protein content
      (legumes, meat, meat analogues) by dietary pattern (vegetarians, non-vegetarians)
      and hip fracture incidence, adjusted for selected lifestyle factors. DESIGN: A
      prospective cohort of Adventist Health Study-2 (AHS-2) enrollees who completed a
      comprehensive lifestyle and dietary questionnaire between 2002 and 2007. SETTING:
      Every two years after enrolment, a short questionnaire on hospitalizations and
      selected disease outcomes including hip fractures was sent to these members.
      SUBJECTS: Respondents (n 33,208) to a baseline and a follow-up questionnaire.
      RESULTS: In a multivariable model, legumes intake of once daily or more reduced
      the risk of hip fracture by 64% (hazard ratio = 0.36, 95% CI 0.21, 0.61) compared
      with those with legumes intake of less than once weekly. Similarly, meat intake
      of four or more times weekly was associated with a 40% reduced risk of hip
      fracture (hazard ratio = 0.60, 95% CI 0.41, 0.87) compared with those whose meat
      intake was less than once weekly. Furthermore, consumption of meat analogues once
      daily or more was associated with a 49 % reduced risk of hip fracture (hazard
      ratio = 0.51, 95% CI 0.27, 0.98) compared with an intake of less than once
      weekly. CONCLUSIONS: Hip fracture incidence was inversely associated with legumes
      intake and, to a lesser extent, meat intake, after accounting for other food
      groups and important covariates. Similarly, a high intake of meat analogues was
      associated with a significantly reduced risk of hip fracture.

PMID- 24103484
TI  - Bilateral lesions of nucleus subpretectalis/interstitio-pretecto-subpretectalis
      (SP/IPS) selectively impair figure-ground discrimination in pigeons.
AB  - Earlier, we reported that nucleus rotundus (Rt) together with its inhibitory
      complex, nucleus subpretectalis/interstitio-pretecto-subpretectalis (SP/IPS), had
      significantly higher activity in pigeons performing figure-ground discrimination
      than in the control group that did not perform any visual discriminations. In
      contrast, color discrimination produced significantly higher activity than
      control in the Rt but not in the SP/IPS. Finally, shape discrimination produced
      significantly lower activity than control in both the Rt and the SP/IPS. In this
      study, we trained pigeons to simultaneously perform three visual discriminations
      (figure-ground, color, and shape) using the same stimulus displays. When birds
      learned to perform all three tasks concurrently at high levels of accuracy, we
      conducted bilateral chemical lesions of the SP/IPS. After a period of recovery,
      the birds were retrained on the same tasks to evaluate the effect of lesions on
      maintenance of these discriminations. We found that the lesions of the SP/IPS had
      no effect on color or shape discrimination and that they significantly impaired
      figure-ground discrimination. Together with our earlier data, these results
      suggest that the nucleus Rt and the SP/IPS are the key structures involved in
      figure-ground discrimination. These results also imply that thalamic processing
      is critical for figure-ground segregation in avian brain. 

PMID- 24103483
TI  - Phosphatidic acid, phospholipase D and tumorigenesis.
AB  - Phospholipase D (PLD) is a membrane protein with a double role: maintenance of
      the structural integrity of cellular or intracellular membranes and involvement
      in cell signaling through the product of the catalytic reaction, PA, and through
      protein-protein interaction with a variety of partners. Cross-talk during PLD
      signaling occurs with other cancer regulators (Ras, PDGF, TGF and kinases).
      Elevation of either PLD1 or PLD2 (the two mammalian isoforms of PLD) is able to
      transform fibroblasts and contribute to cancer progression. Elevated total PLD
      activity, as well as overexpression, is present in a wide variety of cancers such
      as gastric, colorectal, renal, stomach, esophagus, lung and breast. PLD provides
      survival signals and is involved in migration, adhesion and invasion of cancer
      cells, and all are increased during PLD upregulation or, conversely, they are
      decreased during PLD loss of function. Eventhough the end results of PLD action
      as relates to downstream signaling mechanisms are still currently being
      elucidated, invasion, a pre-requisite for metastasis, is directly affected by
      PLD. This review will introduce the classical mammalian PLD's, PLD1 and PLD2,
      followed by the mechanisms of intracellular regulation and a status of current
      investigation in the crucial involvement of PLD in cancer, mostly through its
      role in cell migration, invasion and metastasis, that has grown exponentially in
      the last few years. 

PMID- 24103485
TI  - Maternal behaviour and lamb survival: from neuroendocrinology to practical
      application.
AB  - Parental care promotes offspring survival and, for livestock species, this care
      is provided solely by the mother. Maternal behaviour in the sheep has been
      exceptionally well-studied compared with other species and many of the
      underpinning biological processes leading to the expression of maternal care are
      known. In this review the current state of play with regard to the biology of
      maternal care will be reviewed, and its application to provide practical
      solutions to reduce lamb mortality considered. For maternal care to be elicited
      at birth the ewe requires elevated circulating oestradiol in late gestation,
      which stimulates the expression of oxytocin receptors in both peripheral and
      central areas (particularly the hypothalamic and limbic areas of the brain). At
      birth stretching of the vaginocervical canal elicits a spinal reflex which
      triggers the release of oxytocin primarily from neurones within the
      paraventricular nucleus of the hypothalamus. Oxytocin release causes an increase
      in the neurotransmitters noradrenaline, acetylcholine, glutamate and gamma
      aminobutyric acid (GABA) in the olfactory bulb, and other brain regions important
      for maternal behaviour. Finally, sensory cues provided by the lamb, in particular
      the amniotic fluids surrounding it, lead to the expression of maternal behaviours
      (licking, low-pitched bleats, acceptance of the lamb at the udder and suckling).
      This allows the expression of the two facets of maternal behaviour in the ewe:
      nurturance of the young and maternal selectivity, whereby a specific olfactory
      memory for the ewes own lamb is formed and the expression of maternal care is
      restricted to this lamb. Variation in the expression of maternal care has been
      demonstrated in primiparous ewes compared with multiparous, in different sheep
      genotypes, with undernutrition, stress in pregnancy, following a difficult
      delivery, and may occur with variation in ewe temperament. An understanding of
      the importance of the timing of various events in late pregnancy and during
      parturition, as well as the factors that can disrupt these events, can help to
      design management activities to minimise risks to the successful onset of
      maternal behaviour. Management practices that work with the biology of the ewe
      will be the most successful in ensuring that maternal care is expressed, so
      improving the welfare of the ewe and lamb, and the profitability of the farm. 

PMID- 24103486
TI  - Exploring the impact of augmenting sedation assessment with physiologic monitors.
AB  - BACKGROUND: Pharmacological sedation is a necessary tool in the management of
      critically ill, mechanically ventilated patients. The intensive care unit (ICU)
      sedation strategy is to use the least amount of medication to meet safety and
      comfort goals. Titration of pharmacological agents is currently guided by
      clinical assessment tools. The purpose of this study was to determine whether the
      addition of a neurophysiological monitor, bispectral index (BIS), aided the ICU
      nurse in reducing the amount of drug used, compared to a clinical tool alone, in
      a general critical care population. METHODS: In this prospective clinical trial,
      mechanically ventilated adults (N=300) were randomised to sedation assessment
      using only the observational assessment tool (RASS) or a combination of
      observational and physiologic measures (RASS+BIS). Subjects were enrolled from a
      medical ICU (N=154), a trauma ICU (N=72) and a general mixed-use ICU (N=74).
      RESULTS: BIS-augmented sedation was only associated with the reduction of drug
      use when patients were sedated with propofol or narcotic agents (propofol [1.61
      mg/kg/h vs. 1.77 mg/kg/h; p<0.0001], fentanyl [54.73 mcg/h vs. 66.81 mcg/h;
      p<0.0001], and hydromorphone [0.97 mg/h vs. 4.00 mg/h: p<0.0001] compared to RASS
      alone. In contrast, patients sedated with dexmedetomidine or benzodiazepines were
      given higher doses under the BIS-augmented dexmedetomidine [0.46 mcg/kg/h vs.
      0.33 mcg/kg/h; p<0.0001], lorazepam [4.13 mg/h vs. 3.29 mg/h p<0.0001], and
      midazolam [3.73 mg/h vs 2.86 mg/h; p<0.0001]) protocol compared to clinical
      assessment alone. CONCLUSION: The clinical evaluation of depth of sedation
      remains the most reliable method for the titration of pharmacological sedation in
      the critical care unit. However, BIS-augmented assessment is helpful in reducing
      the amount of propofol and narcotic medication used and may be considered an
      adjunct when these agents are utilised.

PMID- 24103487
TI  - Use of antiplatelet agents in sepsis: a glimpse into the future.
AB  - As mechanisms of sepsis pathophysiology have been elucidated with time, sepsis
      may be considered nowadays, as an uncontrolled inflammatory and pro-coagulant
      response to a pathogen. In this cascade of events, platelets play a key role, via
      interaction with endothelial cells and modulation of both innate and adaptive
      immune system. In that manner, inhibition of platelet function could represent a
      useful tool for attenuating inflammatory response and improving outcomes. Data on
      current antiplatelet agents, including acetylsalicylic acid, P2Y12 inhibitors and
      GPIIb/IIIa antagonists, in animal models are promising. Clinical data in patients
      hospitalized for pneumonia, at risk for acute lung injury, and/or critically ill
      revealed an association between antiplatelet therapy and reduction in both short
      term mortality and prevalence of acute lung injury, as well as, the need for
      intensive care unit admission, without a concomitant increased bleeding risk. In
      need of innovative approach in the treatment of sepsis, further prospective,
      interventional, randomized trials are pivotal to establish potential use of
      antiplatelet agents in this context. 

PMID- 24103488
TI  - The risk of mothers losing an only child in China.
AB  - China's one-child policy has been quite successful in bringing down the country's
      fertility level but has produced a large number of one-child families. The risk
      of one-child families losing their only child has not received enough attention.
      In this paper, using an extension of Goldman & Lord (1983)'s method to measure
      widowhood, period life-table data from China's 2000 population census are used to
      examine age-specific and cumulative probabilities of mothers losing their only
      child. It is found that a mother faces a 14.94% probability of losing a son, and
      12.21% probability of losing a daughter. As the age of first-time mothers
      increases, the probability of losing a child declines. Urban and rural mothers
      have different indices regarding the loss of children. Based on these findings
      the prospects for China's one-child policy are discussed.

PMID- 24103489
TI  - Combinational analysis of linkage and exome sequencing identifies the causative
      mutation in a Chinese family with congenital cataract.
AB  - BACKGROUND: Congenital cataract is a Mendelian disorder that frequently causes
      blindness in infants. To date, various cataract-associated loci have been mapped;
      more than 30 genes have been identified by linkage analysis. However, the
      pathogenic loci in some affected families are still unknown, and new research
      strategies are needed. In this study, we used linkage-exome combinational
      analysis to further investigate the pedigree of a four-generation Chinese family
      with autosomal dominant coralliform cataract. METHODS: We combined whole exome
      sequencing and linkage analysis to identify the causative mutation. The exome
      capture and next-generation sequencing were used to sequence the protein-coding
      regions in the genome of the proband to identify rare mutations, which were
      further screened for candidate mutations in linkage regions. Candidate mutations
      were independently verified for co-segregation in the whole pedigree using Sanger
      sequencing. RESULTS: We identified a C to A transversion at nucleotide position
      c.70 in exon 2 of CRYGD, a cataract-associated gene. This mutation resulted in a
      threonine substitution for proline at amino acid residue 24. CONCLUSIONS: We
      identified a missense P24T mutation in CRYGD that was responsible for coralliform
      cataract in our studied family. Our findings suggest that the combination of
      exome sequencing and linkage analysis is a powerful tool for identifying
      Mendelian disease mutations that might be missed by the classic linkage analysis
      strategy.

PMID- 24103490
TI  - Dysfunction of orbitofrontal and dorsolateral prefrontal cortices in children and
      adolescents with high-functioning pervasive developmental disorders.
AB  - BACKGROUND: Several lines of evidence suggest that dysfunction of the
      dorsolateral prefrontal cortex (DLPFC) and orbitofrontal cortex (OFC) contributes
      to the pathophysiology of pervasive developmental disorders (PDD). The purpose of
      this study was to investigate neuropsychological dysfunctions in both the DLPFC
      and OFC of children and adolescents with high-functioning PDD. METHODS: The Iowa
      gambling task (IGT), which reflects OFC function, and the Wisconsin Card Sorting
      Test (WCST), which reflects DLPFC function, were assigned to 19 children and
      early adolescents with high-functioning PDD and 19 healthy controls matched for
      gender, age, and intelligence. RESULTS: Compared to healthy controls, patients
      with high-functioning PDD displayed poorer performance on the IGT and the WCST.
      CONCLUSIONS: These results indicate that both the DLPFC and OFC could be impaired
      in children and early adolescents with high-functioning PDD.

PMID- 24103491
TI  - New clinical application of high-intensity focused ultrasound: local control of
      synovial sarcoma.
AB  - High-intensity focused ultrasound (HIFU) is playing an increasingly important
      role in cancer therapy. Primary synovial sarcomas of the chest wall are extremely
      rare. We report the first case of noninvasive HIFU therapy for the control of
      synovial sarcoma. A 51-year-old man was diagnosed with spindle cell sarcoma on
      the left chest wall through lumpectomy. After four cycles of chemotherapy, local
      recurrence of the sarcoma was detected. Subsequent extended resection confirmed
      synovial sarcoma. After five cycles of a new chemotherapy option, the sarcoma
      relapsed again. Then the patient received five courses of HIFU; this completely
      ablated the sarcoma without complications. No chemotherapy, radiotherapy, or
      biological therapy has been applied since. Now the patient is stable and has a
      high quality of life. 

PMID- 24103492
TI  - Laboratory testing trends for respiratory syncytial virus, 2007-2011.
AB  - BACKGROUND: Antigen detection tests have been the most common diagnostic assay
      used to detect and diagnose respiratory syncytial virus (RSV). The utility and
      increased sensitivity of polymerase chain reaction (PCR) tests have been
      reported; however, their use in US hospital laboratories is not well
      characterized. OBJECTIVE: To describe changes in RSV test types used by US
      hospital-affiliated laboratories, focusing on PCR testing prevalence. STUDY
      DESIGN: Data were collected from 480 to 666 laboratories each RSV season (2007
      2008 through 2010-2011) across 50 states, the District of Columbia, and Puerto
      Rico. A descriptive analysis was conducted using this convenience sample of RSV
      tests conducted from November to April each season. Total numbers and types of
      RSV tests performed were reported weekly and weekly proportions by test type were
      calculated. Kendall tau rank correlation was used to quantify associations
      between time and proportions of each test type. RESULTS: PCR tests accounted for
      2%, 3%, 16%, and 21% of weekly tests (total range, 381,068-481,654 over 4
      seasons) conducted each season from 2007 to 2011, respectively. The proportion of
      laboratories reporting >=1 PCR tests was 4%, 5%, 10%, and 16%, respectively.
      Decreases in antigen testing and viral culture were similarly observed.
      CONCLUSIONS: Although antigen detection was the predominant test type reported in
      the sample of US hospital laboratories for RSV testing, PCR use increased to >20%
      of tests reported. These results demonstrate the increasing contribution of PCR
      to RSV surveillance. RSV surveillance systems relying solely on antigen detection
      results will not capture an increasing proportion of RSV test results.

PMID- 24103493
TI  - Excess body weight during pregnancy and offspring obesity: potential mechanisms.
AB  - The rates of child and adult obesity have increased in most developed countries
      over the past several decades. The health consequences of obesity affect both
      physical and mental health, and the excess body weight can be linked to an
      elevated risk for developing type 2 diabetes, cardiovascular problems, and
      depression. Among the factors that can influence the development of obesity are
      higher infant weights and increased weight gain, which are associated with higher
      risk for excess body weight later in life. In turn, mother's excess body weight
      during and after pregnancy can be linked to the risk for offspring overweight and
      obesity through dietary habits, mode of delivery and feeding, breast milk
      composition, and through the influence on infant gut microbiota. This review
      considers current knowledge of these potential mechanisms that threaten to create
      an intergenerational cycle of obesity. 

PMID- 24103494
TI  - External conditions inversely change the RNA polymerase II elongation rate and
      density in yeast.
AB  - Elongation speed is a key parameter in RNA polymerase II (RNA pol II) activity.
      It affects the transcription rate, while it is conditioned by the physicochemical
      environment it works in at the same time. For instance, it is well-known that
      temperature affects the biochemical reactions rates. Therefore in free-living
      organisms that are able to grow at various environmental temperatures, such as
      the yeast Saccharomyces cerevisiae, evolution should have not only shaped the
      structural and functional properties of this key enzyme, but should have also
      provided mechanisms and pathways to adapt its activity to the optimal performance
      required. We studied the changes in RNA pol II elongation speed caused by
      alternations in growth temperature in yeast to find that they strictly follow the
      Arrhenius equation, and that they also provoke an almost inverse proportional
      change in RNA pol II density within the optimal growth temperature range (26-37 
      degrees C). Moreover, we discovered that yeast cells control the transcription
      initiation rate by changing the total amount of available RNA pol II.

PMID- 24103495
TI  - Onset of heterogeneity in culture-expanded bone marrow stromal cells.
AB  - Inconsistencies among in vitro and in vivo experiments using adult mesenchymal
      stem cells (MSCs) confound development of therapeutic, regenerative medicine
      applications, and in vitro expansion is typically required to achieve sufficient
      cell numbers for basic research or clinical trials. Though heterogeneity in both
      morphology and differentiation capacity of culture-expanded cells is noted,
      sources and consequences are not well understood. Here, we endeavored to observe
      the onset of population heterogeneity by conducting long-term continuous in vitro
      observation of human adult bone marrow stromal cell (BMSC) populations, a subset
      of which has been shown to be stem cells (also known as bone marrow-derived
      MSCs). Semi-automated identification and tracking of cell division and migration
      enabled construction of cell lineage maps that incorporated cell morphology. We
      found that all BMSCs steadily grew larger over time; this growth was interrupted
      only when a cell divided, producing two equally sized, morphologically similar
      daughter cells. However, a finite probability existed that one or both of these
      daughters then continued to increase in size without dividing, apparently exiting
      the cell cycle. Thus, larger BMSCs are those cells that have exited the normal
      cell cycle. These results hold important implications for MSC in vitro culture
      expansion and biophysical sorting strategies. 

PMID- 24103497
TI  - The long-term cognitive consequences of early childhood malnutrition: the case of
      famine in Ghana.
AB  - We examine the role of early childhood health in human capital accumulation.
      Using a unique data set from Ghana with comprehensive information on individual,
      family, community, school quality characteristics and a direct measure of
      intelligence together with test scores, we examine the long-term cognitive
      effects of the 1983 famine on survivors. We show that differences in intelligence
      test scores can be robustly explained by the differential impact of the famine in
      different parts of the country and the impacts are most severe for children under
      two years of age during the famine. We also account for model uncertainty by
      using Bayesian Model Averaging. 

PMID- 24103498
TI  - Does health insurance improve health?: Evidence from a randomized community-based
      insurance rollout in rural Burkina Faso.
AB  - From 2004 to 2006, a community-based health insurance (CBI) scheme was rolled out
      in Nouna District, Burkina Faso, with the objective of improving access to health
      services and population health. We explore the random timing of the insurance
      rollout generated by the stepped wedge cluster-randomized design to evaluate the
      welfare and health impact of the insurance program. Our results suggest that the
      insurance had limited effects on average out-of-pocket expenditures in the target
      areas, but substantially reduced the likelihood of catastrophic health
      expenditure. The introduction of the insurance scheme did not have any effect on
      health outcomes for children and young adults, but appears to have increased
      mortality among individuals aged 65 and older. The negative health effects of the
      program appear to be primarily driven by the adverse provider incentives
      generated by the scheme and the resulting decline in the quality of care received
      by patients. 

PMID- 24103499
TI  - Prospect theory in the health domain: a quantitative assessment.
AB  - It is well-known that expected utility (EU) has empirical deficiencies.
      Cumulative prospect theory (CPT) has developed as an alternative with more
      descriptive validity. However, CPT's full function had not yet been quantified in
      the health domain. This paper is therefore the first to simultaneously measure
      utility of life duration, probability weighting, and loss aversion in this
      domain. We observe loss aversion and risk aversion for gains and losses, which
      for gains can be explained by probabilistic pessimism. Utility for gains is
      almost linear. For losses, we find less weighting of probability 1/2 and concave
      utility. This contrasts with the common finding of convex utility for monetary
      losses. However, CPT was proposed to explain choices among lotteries involving
      monetary outcomes. Life years are arguably very different from monetary outcomes
      and need not generate convex utility for losses. Moreover, utility of life
      duration reflects discounting, causing concave utility. 

PMID- 24103500
TI  - Useful beautiful minds-an analysis of the relationship between schizophrenia and
      employment.
AB  - This paper examines the relationship between schizophrenia and employment. We use
      longitudinal register data and show a considerable drop in the employment rate
      for people with schizophrenia six years before the first treatment at a
      psychiatric facility. After the first treatment, the employment rate stabilizes
      at 18%. The difference in the employment rate in 2007 for siblings with and
      without schizophrenia is estimated at 67%. This difference is reduced to 62% when
      we include additional control variables. The results remain unchanged when we
      apply a sibling fixed effects approach that controls for the unobserved family
      specific characteristics that the siblings share. 

PMID- 24103496
TI  - Chick stem cells: current progress and future prospects.
AB  - Chick embryonic stem cells (cESCs) can be derived from cells obtained from stage
      X embryos (blastoderm stage); these have the ability to contribute to all somatic
      lineages in chimaeras, but not to the germ line. However, lines of stem cells
      that are able to contribute to the germ line can be established from chick
      primordial germ cells (cPGCs) and embryonic germ cells (cEGCs). This review
      provides information on avian stem cells, emphasizing different sources of cells
      and current methods for derivation and culture of pluripotent cells from chick
      embryos. We also review technologies for isolation and derivation of chicken germ
      cells and the production of transgenic birds. 

PMID- 24103501
TI  - Exploring the intergenerational persistence of mental health: evidence from three
      generations.
AB  - This paper uses data from the 1970 British Cohort Study to quantify the
      intergenerational persistence of mental health, and the long-run economic costs
      associated with poor parental mental health. We find a strong and significant
      intergenerational correlation that is robust to different covariate sets, sample
      restrictions, model specifications and potential endogeneity. Importantly, the
      intergenerational persistence is economically relevant, with maternal mental
      health associated with lasting effects on the child's educational attainment,
      future household income and the probability of having criminal convictions. These
      results do not disappear after controlling for children's own childhood and
      adulthood mental health. 

PMID- 24103502
TI  - Bacterial adhesion to orthopaedic implant materials and a novel oxygen plasma
      modified PEEK surface.
AB  - Despite extensive use of polyetheretherketone (PEEK) in biomedical applications,
      information about bacterial adhesion to this biomaterial is limited. This study
      investigated Staphylococcus aureus and Staphylococcus epidermidis adhesion to
      injection moulded and machined PEEK OPTIMA((r)) using a custom-built adhesion
      chamber with medical grade titanium and Thermanox for comparison. Additionally,
      bacterial adhesion to a novel oxygen plasma modified PEEK was also investigated
      in both a pre-operative model in physiological saline, and additionally in a post
      operative model in human blood plasma. In the pre-operative model, the rougher
      machined PEEK had a significantly greater number of adherent bacteria compared to
      injection moulded PEEK. Bacterial adhesion to titanium and Thermanox was similar.
      Oxygen plasma surface modification of PEEK did not lead to a significant change
      in bacterial adhesion in the pre-operative contamination model, despite observed
      changes in surface characteristics. In the post-operative contamination model, S.
      aureus adhesion was increased from 5*10(5) CFU cm(-2) to approximately 1.3*10(7)
      CFU cm(-2) on the modified surfaces due to differential protein adhesion during
      the conditioning period. However, S. epidermidis adhesion to modified PEEK was
      less than to unmodified PEEK in the post-operative model. These results
      illustrate the importance of testing bacterial adhesion of several strains in
      both a pre-operative and post-operative, clinically relevant bacterial
      contamination model.

PMID- 24103503
TI  - Enhanced doxorubicin delivery and cytotoxicity in multidrug resistant cancer
      cells using multifunctional magnetic nanoparticles.
AB  - Carboxymethyl modified magnetic nanoparticles (CMC-MNPs) have been designed as a
      vehicle for drug delivery in both drug-sensitive and drug-resistant cancer cells.
      We have demonstrated that the CMC-MNPs were able to load doxorubicin (DOX) with a
      high loading efficiency while also maintaining a good colloidal stability in an
      aqueous solution. According to a drug release study, DOX-loaded CMC-MNPs showed
      that the pH-dependent drug release property had a much higher release rate in
      acidic pH. Compared to free DOX, the DOX-loaded CMC-MNPs showed higher DOX
      accumulation in drug-sensitive cancer cells and much higher accumulation in drug
      resistant cancer cells. These results indicate that our nanoplatform is highly
      efficient as a drug delivery system in both normal cancer cells and MDR cancer
      cells. In addition, the DOX-loaded CMC-MNPs can also enhance cytotoxicity against
      drug-resistant cancer cells in comparison to free DOX. The results obtained in
      this research demonstrate that our nanoplatform may be a promising approach in
      cancer chemotherapy and for overcoming multidrug-resistant cancer cells. 

PMID- 24103504
TI  - Toward one-pot lipase-catalyzed synthesis of poly(epsilon-caprolactone) particles
      in aqueous dispersion.
AB  - The preparation of polyester particles using enzyme-catalyzed (lipase from
      Candida antarctica B, CALB) ring-opening polymerization of epsilon-caprolactone
      (epsilon-CL) in aqueous dispersion was demonstrated for the first time.
      Immobilization of CALB enabled a significant increase of the number-average
      degree of polymerization of epsilon-CL oligomers (up to 38) as compared to
      dissolved CALB (8 at the maximum). The nature and amount of lipase, as well as
      the nature of the support material were identified as key parameters controlling
      ring-opening polymerization of epsilon-CL in aqueous dispersion. In addition, the
      involvement of solubilized monomers in polymerization elementary reactions was
      demonstrated and the consequences on oligomers average length were detailed. An
      overall mechanism of lipase-catalyzed epsilon-CL polymerization in aqueous
      dispersion taking into account the colloidal nature of reaction medium was
      proposed on the basis of experimental results.

PMID- 24103505
TI  - Preparation and characterization of thiophilic cryogels with 2-mercapto ethanol
      as the ligand for IgG purification.
AB  - In this study, thiophilic cryogels were prepared by two different approaches and
      they were used in purification of IgG from aqueous solutions and human plasma. In
      the first approach, poly(2-hydoxyethyl methacrylate) [PHEMA] cryogel disks were
      prepared. The PHEMA cryogel disks were activated by divinylsulfone (DVS) and 2
      mercapto ethanol was attached. In the second approach, poly(2-hydroxyethyl
      methacrylate-etylene glycol dimethacrylate) [P(HEMA-EGDMA)] beads were
      synthesized and 2-mercapto ethanol was attached to the beads as a thiophilic
      ligand. In order to increase the surface area, P(HEMA-EGDMA)/PHEMA composite
      cryogel disks were prepared by embedding the P(HEMA-EGDMA) beads into PHEMA
      cryogels. Both the thiophilic PHEMA (T-PHEMA) cryogel disks and the thiophilic
      P(HEMA-EGDMA)/PHEMA [T-P(HEMA-EGDMA)/PHEMA] composite cryogel disks were
      characterized by Fourier transform infrared spectroscopy, surface area
      measurements, elemental analysis, swelling tests and scanning electron
      microscopy. The effects of salt concentration, pH, temperature, initial IgG
      concentration were analysed for IgG adsorption from aqueous solutions in batch
      mode. When lyotropic salt, Na2SO4, was used, the adsorption capacity was 27.5
      mg/g and 68.7 mg/g for T-PHEMA and the T-P(HEMA-EGDMA)/PHEMA composite cryogel
      disks, respectively. 1.0 M NaCl was used as desorption agent. The change in
      adsorption capacity was not remarkable for a repetition of adsorption-desorption
      cycle ten times. Both the thiophilic cryogel disks and the thiophilic composite
      cryogel disks were also successfully used for IgG isolation from human plasma.
      The purity assayed by SDS-PAGE was 89%. The adsorption capacities were 74.8 mg/g
      and 137.4 mg/g in human plasma samples for the T-PHEMA cryogel disks and the T
      P(HEMA-EGDMA)/PHEMA composite cryogel disks, respectively.

PMID- 24103506
TI  - Boot swabs to collect environmental samples from common locations in dairy herds
      for Mycobacterium avium ssp. paratuberculosis (MAP) detection.
AB  - The aim of the present study was the examination of the boot swab sampling
      technique for the collection of environmental material in order to identify
      Mycobacterium avium ssp. paratuberculosis (MAP)-infected herds. Eight dairy herds
      were included into the study. Four of them had a well-known history of MAP
      infection from a herd surveillance programme conducted since 2006. Cows in these
      herds were repeatedly tested positive in Pourquier(r) MAP-ELISA (Pourquier,
      Montepellier, France); in some MAP could be isolated in individual faecal culture
      despite that symptoms of paratuberculosis were never reported. In four presumably
      negative herds nearly all cows were repeatedly tested serologically negative for
      MAP. The pathogen was never isolated from faecal samples of cows by culture. The
      study was initiated with the aim of standardising environmental samples as a herd
      diagnostics, in which overall 130 pairs of boot swab samples from the cows'
      surroundings were taken In 58 of 64 swab samples (90.6%) from confirmed MAP
      infected herds the organism could be isolated by mycobacterial culture of the
      boot swab. Contrarily, in 66 samples from presumably MAP-negative herds only one
      swab was positive (1.5%). The utilisation of boot swabs as a standardised
      technique for environmental sampling offers an effective and inexpensive tool for
      identifying herds infected with MAP. This is the first report of using boot swabs
      for the collection of environmental samples for MAP- detection in cattle herds.
      This easy to perform technique enables the economical detection of MAP herd
      status. 

PMID- 24103507
TI  - Osmium tetroxide labeling of (poly)methyl methacrylate corrosion casts for
      enhancement of micro-CT microvascular imaging.
AB  - In order to enhance micro-computer tomography (micro-CT) imaging of corrosion
      casts of fine vasculature, metals can be added to the casting resin before
      perfusion. However, perfused metals lead to vasoconstriction or vessel damage
      resulting in nonphysiologic vascular casts. A novel method for coating methyl
      methacrylate vascular casts with osmium tetroxide has been developed in order to
      increase micro-CT contrast without affecting the vascular structure. This
      technique was verified using corrosion casts of the lung vasculature of New
      Zealand white rabbits. Osmium tetroxide coating of methyl methacrylate vascular
      corrosion casts resulted in an increase in overall sample contrast that
      translated into an increase in the resolution of the vasculature. This method can
      therefore lead to increased resolution in the characterization of fine vascular
      structures. 

PMID- 24103508
TI  - FRED (a Framework for Reconstructing Epidemic Dynamics): an open-source software
      system for modeling infectious diseases and control strategies using census-based
      populations.
AB  - BACKGROUND: Mathematical and computational models provide valuable tools that
      help public health planners to evaluate competing health interventions,
      especially for novel circumstances that cannot be examined through observational
      or controlled studies, such as pandemic influenza. The spread of diseases like
      influenza depends on the mixing patterns within the population, and these mixing
      patterns depend in part on local factors including the spatial distribution and
      age structure of the population, the distribution of size and composition of
      households, employment status and commuting patterns of adults, and the size and
      age structure of schools. Finally, public health planners must take into account
      the health behavior patterns of the population, patterns that often vary
      according to socioeconomic factors such as race, household income, and education
      levels. RESULTS: FRED (a Framework for Reconstructing Epidemic Dynamics) is a
      freely available open-source agent-based modeling system based closely on models
      used in previously published studies of pandemic influenza. This version of FRED
      uses open-access census-based synthetic populations that capture the demographic
      and geographic heterogeneities of the population, including realistic household,
      school, and workplace social networks. FRED epidemic models are currently
      available for every state and county in the United States, and for selected
      international locations. CONCLUSIONS: State and county public health planners can
      use FRED to explore the effects of possible influenza epidemics in specific
      geographic regions of interest and to help evaluate the effect of interventions
      such as vaccination programs and school closure policies. FRED is available under
      a free open source license in order to contribute to the development of better
      modeling tools and to encourage open discussion of modeling tools being used to
      evaluate public health policies. We also welcome participation by other
      researchers in the further development of FRED.

PMID- 24103509
TI  - Thalamocortical mechanisms for integrating musical tone and rhythm.
AB  - Studies over several decades have identified many of the neuronal substrates of
      music perception by pursuing pitch and rhythm perception separately. Here, we
      address the question of how these mechanisms interact, starting with the
      observation that the peripheral pathways of the so-called "Core" and "Matrix"
      thalamocortical system provide the anatomical bases for tone and rhythm channels.
      We then examine the hypothesis that these specialized inputs integrate acoustic
      content within rhythm context in auditory cortex using classical types of
      "driving" and "modulatory" mechanisms. This hypothesis provides a framework for
      deriving testable predictions about the early stages of music processing.
      Furthermore, because thalamocortical circuits are shared by speech and music
      processing, such a model provides concrete implications for how music experience
      contributes to the development of robust speech encoding mechanisms.

PMID- 24103510
TI  - Mineral status of non-anemic Peruvian infants taking an iron and copper syrup
      with or without zinc from 6 to 18 months of age: a randomized controlled trial.
AB  - OBJECTIVES: We evaluated changes in the status of iron, zinc, and copper in non
      anemic Peruvian infants who were receiving daily supplements of 10 mg of iron and
      0.5 mg of copper with or without 10 mg of zinc from 6 to 18 mo of age. METHODS:
      Overall, 251 infants were randomized to receive one of two daily supplements.
      Venous blood draws at 6, 12, and 18 mo of age were taken to characterize
      hemoglobin, plasma ferritin, zinc, and copper concentrations. The urinary
      excretion of zinc was also measured at each time point. Repeated measures
      analysis of variance was used to evaluate changes over time and by supplement
      type. RESULTS: Both hemoglobin and copper concentrations increased significantly
      and plasma ferritin decreased from 6 to 12 mo of age (P < 0.05). Mean plasma zinc
      concentrations in the zinc treatment group were maintained over time, whereas
      zinc concentrations in the control group declined; differences by treatment were
      found at 12 and 18 mo of age (P < 0.05). Urinary zinc concentration was increased
      in the zinc group at 12 mo only. There was evidence that zinc treatment improved
      the hemoglobin level at 18 mo of age (P = 0.09). Compliance with supplementation
      was high, with 81% of the intended dose consumed over the 12-mo period.
      CONCLUSIONS: Daily mineral supplementation over the course of 1 y appears to be
      feasible and acceptable in this population. A combined supplement can improve the
      status of iron, zinc, and copper in infants at the same time.

PMID- 24103511
TI  - Influence of a nutritional intervention on dietary intake and quality of life in
      cancer patients: a randomized controlled trial.
AB  - OBJECTIVE: Weight loss is common in patients with malignant tumors and it can
      adversely affect quality of life and survival. The aim of the present study was
      to investigate the effects of a nutritional intervention in cancer patients in an
      outpatient setting. METHODS: Cancer outpatients (N = 58) who were classified as
      undernourished or at high risk for undernutrition by the Nutritional Risk
      Screening 2002 tool were randomized into two groups. One group (n = 30) received
      standardized individual nutritional therapy, including counseling by a dietitian,
      food fortification, and oral nutritional supplements if required. The second
      group (n = 28) received standard care. The nutritional intervention lasted 3 mo.
      Dietary intake (3-d dietary record), nutritional status (body weight), physical
      functioning (performance status, hand-grip strength) and quality of life
      (European Organization for Research and Treatment of Cancer Quality of Life
      Questionnaire version 3.0) were assessed at baseline and after 6 wk and 3 mo. An
      additional follow-up assessment was carried out 3 mo post-intervention. RESULTS:
      Nutritional intervention led to a significantly higher average energy and protein
      intake in the nutritional therapy group (+379 kcal; 95% confidence interval [CI],
      117-642; P = 0.007, respectively; +10.4 g; 95% CI, 2.3-18.5; P = 0.016). However,
      the increased dietary intake was not associated with improvements in nutritional
      status, physical functioning, or quality of life. CONCLUSIONS: Individual
      nutritional counseling significantly and positively influenced energy and protein
      intake, but did not improve nutritional or physical outcome or quality of life.
      These results indicate that nutritional therapy alone is of limited efficacy in
      cancer patients whose nutritional status has already deteriorated.

PMID- 24103512
TI  - Energy density, diet quality, and central body fat in a nationwide survey of
      young Spaniards.
AB  - OBJECTIVES: To determine the impact of energy density on diet quality and
      anthropometric proxy measures for central body fat in young Spaniards. METHODS:
      Data were obtained from a representative national sample of 2513 young Spaniards
      aged 10 to 24 y. Dietary assessment was performed with a 24-h recall. Adherence
      to the Mediterranean diet was measured by the KIDMED index. Reduced rank
      regression analysis was used to identify energy-density dietary patterns. Waist
      circumferences and height were measured. RESULTS: Pastries and sausages showed
      the strongest loading for the dietary energy density factor score (DED-FS), with
      fruits and vegetables at the opposite end of the scale. Multiple linear
      regression analysis showed a positive association (P < 0.01) of dietary energy
      density (DED) and the DED-FS with waist circumferences regressed on height and
      age (WCheight+age) and waist-to-height ratio (WHtR). The adjusted odds ratio for
      elevated WCheight+age and WHtR increased across quartile distribution of DED (P <
      0.001) and DED-FS (P < 0.05). Diet quality characterized by the KIDMED index was
      negatively associated (P < 0.001) with DED and the DED-FS. CONCLUSIONS: Higher
      DED is a risk for increased central fat distribution and is associated with low
      adherence to the Mediterranean diet.

PMID- 24103513
TI  - The STRONG(kids) nutritional screening tool in hospitalized children: a
      validation study.
AB  - OBJECTIVE: The STRONGkids is a nutritional screening tool for hospitalized
      children, which was found to predict a negative weight for height (WFH) standard
      deviation score (SDS) and a prolonged hospital length of stay (LOS) in a Dutch
      population of hospitalized children. This study aimed to test the ease of use and
      reproducibility of the STRONGkids, and to confirm its concurrent and prospective
      validity in a Belgian population of hospitalized children. METHODS:
      Reproducibility was tested in a cohort of 29 hospitalized children in a tertiary
      center and validity was tested in 368 children (105 hospitalized in a tertiary
      and 263 in three secondary hospitals) ages between 0.08 and 16.95 y (median 2.2
      y). RESULTS: Substantial intrarater (kappa = 0.66) and interrater (kappa = 0.61)
      reliabilities were found between observations. STRONGkids scores correlated
      negatively with WFH SDS of the patients (rho = -0.23; P < 0.01; odds ratio [OR],
      2.47; 95% confidence interval [CI], 1.11-5.49; P < 0.05). It had a sensitivity
      and negative predictive value (NPV) of respectively 71.9% and 94.8% to identify
      acutely undernourished children. STRONGkids did not correlate with weight loss
      during hospitalization, but correlated with LOS (rho = 0.25; OR 1.96; 95% CI,
      1.25-3.07; both P < 0.01) and the set-up of a nutritional intervention during
      hospitalization (OR, 18.93; 95% CI, 4.48-80.00; P < 0.01). The sensitivity and
      NPV to predict a LOS >= 4 d were respectively 62.6% and 72%, and respectively
      94.6% and 98.9% to predict a nutritional intervention. CONCLUSIONS: STRONGkids is
      an easy-to-use screening tool. Children classified as "low risk" have a 5%
      probability of being acutely malnourished, with only a 1% probability of a
      nutritional intervention during hospitalization.

PMID- 24103514
TI  - Effect of television viewing on food and nutrient intake among adolescents.
AB  - OBJECTIVE: Among the behaviors associated with food intake, exposure to
      television is particularly important given the number of adolescents exposed.
      Also, increased time spent watching television has been associated with physical
      inactivity and with less desirable dietary intake among adolescents. The aim of
      this study was to examine the association between television viewing and dietary
      intake among 13-y-old adolescents. METHODS: A cross-sectional evaluation was
      carried out in the 2003-2004 school year, including adolescents born in 1990 and
      enrolled in the schools of Porto, Portugal. Time spent watching TV was collected
      by self-administered questionnaires and dietary intake was evaluated using a food
      frequency questionnaire. Included in the analysis were 1436 adolescents. RESULTS:
      Spending more than 120 min per day watching TV was significantly associated with
      higher intake of total fat and polyunsaturated fat and with lower intake of
      magnesium, in both sexes. Additionally, in girls, spending more than 120 min per
      day watching TV was associated with lower intake of complex carbohydrates, fiber,
      total vitamin A, folate, vitamin C, calcium, iron, phosphorus, and potassium. In
      boys, higher intake of saturated fat and cholesterol was found among those
      spending more time watching TV. CONCLUSIONS: We found that television viewing is
      associated with higher consumption of foods containing more fats and sugars and a
      lower consumption of fruits and vegetables. Consequently, adolescents who watched
      more television had a higher intake of total fat and polyunsaturated fat and a
      lower intake of minerals and vitamins. This dietary behavior among adolescents
      may have long-term health implications, not only limited to obesity.

PMID- 24103515
TI  - The use of oral rehydration salt in managing children under 5 y old with diarrhea
      in the Gambia: knowledge, attitude, and practice.
AB  - OBJECTIVE: Diarrhea is a leading cause of mortality in children under the age of
      5 y in developing countries. To our knowledge, no other studies have investigated
      the management of diarrhea in the Gambia. The aim of this study was to assess
      maternal knowledge, attitude, and practice in the causes, prevention, and
      management of diarrhea in children under the age of 5 y in the Gambia. METHODS:
      Four hundred mothers with children who have diarrhea and are under the age of 5 y
      were randomly recruited. Data were collected using structured questionnaires,
      including demographic information, knowledge about diarrhea, attitude toward the
      management of diarrhea, and practice for the prevention and management of
      diarrhea. chi(2) and Student's t tests were used for the descriptive and
      quantitative analysis, respectively. Simple and multiple linear regressions were
      used to determine the association between the variables. A P-value < 0.05 was
      considered statistically significant. RESULTS: The mean of maternal knowledge
      (K), attitude (A), practice (P), and knowledge-attitude-practice sum (KAP) scores
      were 14.4, 6.3, 13.2, and 33.9, respectively. The mean of knowledge scores were
      significantly higher in mothers who responded positively for germs (13.4 versus
      12.6) and dirty hands (13.7 versus 13.0) as causes of diarrhea. Mothers with
      education had significantly higher knowledge (14.7 versus 14.2) and attitude
      scores (6.6 versus 6.1) in management of diarrhea. However, the study found a low
      use rate (4%) of oral rehydration solution in practice. Multiple linear
      regression analysis revealed that maternal age was positively associated with
      practice (beta = 0.061) and KAP scores (beta = 0.102). The number of children in
      the family was positively correlated with attitude scores (beta = 0.408).
      Socioeconomic status was positively associated with attitude (beta = 0.549),
      practice (beta = 0.841), and KAP scores (beta = 1.887). CONCLUSIONS: The mothers
      have high knowledge scores in the management of diarrhea; however, use of oral
      rehydration solution is low among children with diarrhea under the age of 5 y in
      the Gambia. Higher maternal age and socioeconomic status are correlated with
      higher practice and KAP scores.

PMID- 24103516
TI  - Distinct effects of leucine or a mixture of the branched-chain amino acids
      (leucine, isoleucine, and valine) supplementation on resistance to fatigue, and
      muscle and liver-glycogen degradation, in trained rats.
AB  - OBJECTIVE: The aim of this study was to evaluate the effects of the mixture of
      branched-chain amino acids (BCAAs) supplementation compared with leucine
      administered orally on muscle biochemical parameters of trained rats submitted to
      an exercise-induced protocol of glycogen depletion. METHODS: After 6 wk of
      swimming exercise, 8 wk-old (250 g, adult) male Wistar rats were randomly divided
      into three experimental groups (n = 8 per group): the mixture of BCAAs (BCAAs),
      leucine (LEU), and placebo (PLA). All groups were submitted to swimming exercise
      for 6 wk and supplemented with either the mixture of BCAAs, leucine, or placebo
      during the last week of training. At week 7 of the protocol, the rats were
      submitted to an intermittent, progressive swimming test until exhaustion and
      sacrificed. Muscle gastrocnemius and liver were depicted to determine total
      glycogen, tricarboxylic acid cycle (TCA) intermediates, and enzymatic activities.
      Statistical evaluation was performed by one-way analysis of variance with Tukey
      post hoc test. RESULTS: Both muscle and liver glycogen degradation ratio were
      significantly higher in the mixture of BCAAs group compared to the PLA group (P <
      0.05) and the LEU group presented decreased liver glycogen degradation ratio
      compared with the mixture of BCAAs group (P < 0.05). Both muscle and liver
      glycogen content were significantly spared in the mixture of BCAAs and LEU groups
      compared to the PLA group (P < 0.01). A performance test demonstrated that LEU
      supplementation enhanced resistance to exhaustion compared to the mixture of
      BCAAs (P < 0.001), however, no difference was found when LEU supplementation was
      compared to PLA (P > 0.05) Muscle citrate content was significantly higher in the
      mixture of BCAAs group compared with the PLA group (P < 0.001). Muscle malate
      content was significantly elevated in the mixture of BCAAs group compared with
      both the PLA (P < 0.001) and LEU groups (P < 0.001). BCAT activity was
      significantly reduced in the mixture of BCAAs supplementation group compared with
      the LEU group (P < 0.001). CONCLUSION: Leucine supplementation improved
      performance compared with the mixture of BCAAs supplementation, sparing muscle
      glycogen stores despite the augmentation of some TCA intermediate concentrations
      on the left side of the TCA cycle.

PMID- 24103517
TI  - Trigonelline isolated from fenugreek seed protects against isoproterenol-induced
      myocardial injury through down-regulation of Hsp27 and alphaB-crystallin.
AB  - OBJECTIVE: Protective effects of trigonelline (TRG) isolated from fenugreek seed
      were evaluated in isoproterenol (ISO)-induced myocardial dysfunctions in adult
      rats and a proteomic approach was applied to understand its mechanism of action.
      METHODS: In a preliminary experiment, effects of TRG at 20, 40, and 80 mg/kg for
      20 d were studied in ISO-induced (100 mg/kg) adult rats. As 40 mg/kg was found
      the most effective concentration, in the final experiment, effects of 40 mg/kg of
      the test drug were investigated using different indices including cardiac marker
      enzymes, lipid peroxidation, antioxidants, cardiac histology, and
      electrocardiogram. Proteomic analyses were also done in cardiac myocytes.
      RESULTS: ISO administration increased serum levels of cardiac markers (creatine
      kinase-MB, glutamate pyruvate transaminase, and lactate dehydrogenase) and
      exhibited a positive reaction in the TROP-T test. It also increased the cardiac
      lipid peroxidation and decreased the cellular antioxidants. Proteomic data
      revealed nine protein spots, seven were down-regulated and two up-regulated. The
      overexpressions of two small stress proteins, heat shock protein (Hsp)27 and
      alphaB crystallin were confirmed by Western blot analysis. All these alterations
      were restored to nearly normal values in 40 mg/kg of TRG-pretreated animals,
      suggesting its cardioprotective effects, which were further confirmed by
      histologic examinations and triphenyl tetrazolium chloride staining assay.
      CONCLUSION: For the first time, our study revealed the down-regulation of Hsp27
      and alphaB-crystallin and (CaMKII delta) isoform by TRG. As the test compound
      prevented the ISO-induced myocardial injury, its therapeutic use may further be
      explored.

PMID- 24103518
TI  - L-Threonine induces heat shock protein expression and decreases apoptosis in heat
      stressed intestinal epithelial cells.
AB  - OBJECTIVES: Osmotically acting amino acids can be cytoprotective following
      injury. As threonine (THR) induces osmotic cell swelling, our aim was to
      investigate the potential for THR to induce cellular protection in intestinal
      epithelial cells and evaluate possible mechanisms of protection. METHODS: Cells
      treated with a range of THR doses were evaluated following heat stress (HS)
      injury. Alpha-aminoisobutyric acid (AIB), a non-metabolizable amino acid analog,
      was used as an osmotic control. MTS assays were used to assess cell survival.
      Heat shock protein (HSP) expression and cleaved caspase-3 (CC3) were evaluated
      via Western blot. Cell morphology and cell size were analyzed via microscopy.
      RESULT: Following HS, THR treatment increased cell viability in a dose dependent
      manner vs. non-THR treated cells (CT). The non-metabolized amino acid analogue,
      AIB, also increased cell survival in heat-stressed cells versus HS controls.
      HSP70 and HSP25 expression increased with THR and AIB treatment versus HS
      controls. THR also increased HSP25 in non-stressed cells. Microscopic evaluation
      revealed both THR and AIB preserved the structural integrity of the actin
      cytoskeleton in heat-stressed cells versus HS controls. THR, but not AIB,
      enhanced nuclear translocation of HSP25 during HS. This nuclear translocation was
      associated with a 60% decrease in apoptosis in heat-stressed cells with THR. No
      antiapoptotic effect was observed with AIB. CONCLUSIONS: This is the first
      demonstration that THR increases HSP70 and HSP 25 and protects cells from HS.
      THR's mechanism of protection may involve cytoskeletal stabilization, HSP up
      regulation and nuclear translocation, and decreased apoptosis. THR's protection
      appears to involve both cell-swelling-dependent and -independent processes.

PMID- 24103519
TI  - Age-related macular degeneration: Effects of a short-term intervention with an
      oleaginous kale extract--a pilot study.
AB  - OBJECTIVE: Age-related macular degeneration (AMD) is a multifactorial
      degenerative disease of the retina, which accounts for slowly progressive visual
      impairment in the elderly. An increased dietary intake of xanthophylls is
      suggested to be inversely related to the risk of macular disease. METHODS: The
      present study was designed as a randomized, double-blind, placebo-controlled,
      parallel trial examining the influence of a short-term intervention with an
      oleaginous extract of Brassica oleracea var. sabellica L. (kale) on plasma
      xanthophyll concentrations and the optical density of the macular pigment
      xanthophylls (MPOD). Twenty patients with non-exudative AMD were recruited for a
      10-wk study period (2-wk run-in, 4-wk intervention, 4-wk washout). All
      participants received 50 mL of a beverage containing either an oleaginous extract
      of kale (kale) or refined rapeseed oil (placebo). The verum product provides 10
      mg lutein and 3 mg zeaxanthin per day. RESULTS: The concentrations of the
      xanthophylls in plasma and the MPOD increased significantly in the kale group
      after 4 wk of intervention. The successive washout period resulted in a
      significant decline of the values in plasma and macula. The values at the end of
      the study were still significantly higher than the initial values. Nevertheless,
      the improvements did not persist over 4 wk of washout. CONCLUSION: The
      distribution of the xanthophylls in the macula seems to be more dynamic than
      originally assumed.

PMID- 24103520
TI  - Nutrition therapy using a multidisciplinary team improves survival rates in
      patients with liver cirrhosis.
AB  - OBJECTIVES: Very few reports thus far have clinically elucidated the advantages
      of a nutrition support team (NST) in the field of liver diseases. The present
      study retrospectively analyzed whether nutrition therapy for liver cirrhosis
      (LC), performed by a multidisciplinary team that includes registered dieticians,
      improves survival rates. METHODS: In study 1, we compared survival rates between
      two groups of patients with LC to elucidate the effects of nutrition management
      by registered dieticians. The first group was comprised of 101 patients that
      received no dietary counseling from a dietician, and the second group was
      comprised of 133 patients that received nutritional counseling following
      nutrition assessment. In study 2, we split the patients who received nutritional
      counseling in study 1 into two groups and compared their survival rates with the
      objective of investigating the effects of a multidisciplinary team approach on
      survival rate. The first group was comprised of 51 patients that, in addition to
      regular nutritional counseling given by a dietician, regularly attended courses
      on liver disease given every 3 to 6 mo. The second group was comprised of 82
      patients that did not attend the liver-disease courses. RESULTS: During study 1,
      34 patients in the first group and 20 patients in the second group died,
      representing a significant difference (P < 0.05). This difference was even more
      pronounced in the subset of patients classified as Child-Pugh class A (P < 0.01),
      but no differences were seen among patients in classes B and C (P = 0.378).
      During study 2, four patients in the first group and 15 patients in the second
      group died, representing a significant difference (P < 0.05). CONCLUSIONS: This
      study showed that nutritional intervention using a multidisciplinary team during
      the treatment of LC improves survival rates and quality of life of the patients.

PMID- 24103521
TI  - Effect of coenzyme Q10 evaluated by 1990 and 2010 ACR Diagnostic Criteria for
      Fibromyalgia and SCL-90-R: four case reports and literature review.
AB  - Recently, Coenzyme Q10 (CoQ10) deficiency has been implicated in the
      pathophysiology of fibromyalgia (FM). It is our objective to present the findings
      of the FM evaluation before and after oral CoQ10 treatment using the American
      College of Rheumatology (ACR) Diagnostic Criteria of 1990 and 2010, and Symptom
      Checklist-Revised (Scl-90-R). Four patients with FM were examined using the
      trigger points, the Fibromyalgia Impact Questionnaire, visual analog scale (pain,
      fatigue, and sleep), Widespread Pain Index, symptom severity scale, and Scl-90-R.
      Previously, CoQ10 contents from patients were analyzed by high-performance liquid
      chromatography. All patients showed CoQ10 deficiency. All patients meet the ACR
      1990 and 2010 criteria. After treatment, all patients showed an important
      improvement in clinical symptoms in all evaluation methods. According to our
      results, and evaluated by three methods, patients with FM are candidates for
      treatment with CoQ10. However, more controlled clinical trials and investigations
      are needed to clarify the precise mechanism(s) by which CoQ10 may contribute in
      pathological and therapeutic processes of FM and to provide data on its
      effectiveness in FM. 

PMID- 24103522
TI  - Pellagra in a child--a rare entity.
AB  - This case has been presented as pellagra, which is very rare in children.
      Pellagra is due dietary deficiency of niacin. Usually seen in alcoholics,
      malabsorption syndromes occur very rarely in children. A 11-y-old girl presented
      with well-defined, hyperpigmented, hyperkeratotic, symmetrical, thick scaly
      plaques surrounded by erythema on the dorsum of the hands, arms, feet, legs up to
      knees, and along the sides of the neck. The child was given 100 mg of
      Nicotinamide. Skin lesions resolved rapidly with the treatment and the child
      improved. 

PMID- 24103523
TI  - Selenium pharmaconutrition in sepsis: to give or not to give? Is this still the
      question?

PMID- 24103524
TI  - CD24 and Nanog identify stem cells signature of ovarian epithelium and cysts that
      may develop to ovarian cancer.
AB  - Ovarian cancer is the most lethal gynecological cancer. There is a general debate
      whether ovarian cancer is an intrinsic or an imported disease. We investigated
      whether in normal morphological appearance and in early stages of ovarian
      tumorgenesis typical cancer cell markers such as CD24 and Nanog are expressed. In
      25% of normal appearing ovaries of post-menopausal women there was co
      localization of CD24 and Nanog in the walls of the ovarian cysts, leaving the
      epithelial cells on the surface of these ovaries free of Nanog or CD24
      expression. In benign ovarian tumors 37% of specimens were positive to CD24 and
      Nanog labeling while 26% of them were localized in the cyst walls. In contrast,
      in serous borderline tumors 79% specimens were labeled with CD24, 42% of them
      were localized in cysts and in 32% of them showed co-localization with CD24 and
      Nanog was evident: the rest were labeled in the ovarian epithelial cells. In
      serous ovarian carcinomas 81% specimens were labeled with CD24 antibodies. In 45%
      of them co-localization with Nanog was evident in the bulk of the cancerous
      tissue. In mucinous carcinomas no labeling with CD24 or Nanog was evident. In
      view of the synergistic effect of CD24 and Nanog expressed in malignant cancer
      development in other systems, it is suggested that such an analysis can be
      valuable for early detection of ovarian cancer. Moreover, the abundance of these
      markers in cysts in the development of ovarian cancer may suggest that they
      present an intrinsic source of the development of the highly malignant disease.
      Finally, since CD24 is exposed on the surface of the cancer cells, it may be
      highly beneficial to target these cells with antibodies to CD24 conjugated to
      cytotoxic drugs for more efficient treatment of this malignant disease. 

PMID- 24103525
TI  - Histological and histochemical investigations of the pharyngeal jaw apparatus of
      a carp Cirrhinus mrigala.
AB  - The histological organization and histochemical aspects of the pharyngeal jaw
      apparatus of the Indian major carp Cirrhinus mrigala are described. The
      pharyngeal jaw apparatus consists of a lower pharyngeal jaw and a chewing pad.
      Histochemical analysis reveals that the epithelium covering the lower pharyngeal
      jaw is mucogenic and is involved in the secretion of different classes of
      glycoproteins (GPs) including GPs with oxidizable vicinal diols, GPs with O
      sulphate esters and GPs with sialic acid residues with and without O-acyl
      substitution. Characteristically, the epithelium at irregular intervals is
      differentiated into simple or branched tubular pharyngeal glands, which often
      extend deep into the sub-epithelial tissues. Copious mucus secretion from
      pharyngeal glands may be associated with transportation of chewed food particles
      toward the esophagus. Histochemistry and fluorescence microscopy show that the
      epithelium covering the chewing pad is keratinized. The keratinized surface of
      the chewing pad may be considered to serve as an occlusion surface for the lower
      pharyngeal jaw teeth forming an efficient pharyngeal mill for chewing food
      materials. 

PMID- 24103526
TI  - Social influences on eating: implications for nutritional interventions.
AB  - We review recent research on the effect of social context on food intake and food
      choice and assess the implications for nutritional interventions. We focus on
      studies of modelling of eating behaviour and the impact of perceived eating norms
      on the amounts and types of food that individuals eat. We suggest that social
      context influences eating via multiple mechanisms, including identity signalling
      and self-presentation concerns. However, building on existing theoretical models,
      we propose that social factors may be particularly influential on nutrition
      because following the behaviour of others is adaptive and social norms inform
      individuals about behaviours that are likely to be optimal ('if everyone else is
      doing it, I probably should be'). Guided by understanding of the potential
      underlying mechanisms, we discuss how social norms might be used to promote
      healthier nutrition. 

PMID- 24103527
TI  - Role of ovarian secretions in mammary gland development and function in
      ruminants.
AB  - The mammary gland is a dynamic organ that undergoes cyclic developmental and
      regressive changes during the lifetime of a female mammal. Mammogenesis begins
      during embryonic life with the development of the first mammary gland rudiments
      and ductal system. After birth, during the pre-pubertal period, the ductal growth
      of the mammary parenchyma occurs through the fat pad. In most of the ruminant
      species allometric mammary parenchyma development begins with the onset of cyclic
      ovarian secretions activity. The two main hormones secreted during an ovarian
      cycle are estradiol and progesterone. These steroid hormones are derived from
      cholesterol and are synthesized by theca and granulosa cells in ovaries. During
      puberty, the mammary parenchyma develops in a compact, highly arborescent
      parenchymal mass surrounded by a dense connective matrix. Ductal elongation and
      lobulo-alveolar development are accomplished during growth and pregnancy to
      prepare for future milk production. At the end of lactation, the mammary gland
      undergoes involution, which corresponds to a regression of the secretory tissue,
      a reduction in the alveolar size and a loss of mammary epithelial cells (MECs).
      Ovarian steroids (estradiol and progesterone) appear to be key regulators of the
      different stages of mammogenesis and mammary function. Through this review, the
      role and the importance of ovarian steroids on mammary gland and on MECs is
      described. 

PMID- 24103528
TI  - Identification of exon 19 and 21 mutations of EGFR gene in Chinese patients with
      esophageal squamous cell carcinoma.
AB  - BACKGROUND: Although epidermal growth factor receptor (EGFR) inhibitor treatment
      showed modest response in several clinical trials in esophageal squamous cell
      carcinoma (ESCC) patients, it has been reported that the frequency of EGFR
      mutations varied largely. The aim of this study was to investigate the existence
      of EGFR mutations in Chinese esophageal squamous cell carcinomas. METHODS:
      Formalin-fixed paraffin-embedded surgically resected tumor samples were obtained
      from 127 randomly selected Chinese patients with ESCC. The most common EGFR
      mutations, including in-frame deletions in exon 19 and base substitutions in exon
      21, were detected by denaturing high performance liquid chromatography (DHPLC)
      and direct sequencing simultaneously. K-RAS mutations in codons 12 and 13 were
      detected by direct sequencing. RESULTS: In this study, L858R missense mutations
      of the EGFR gene were found in 8 out of 127 patients (6.3%) by DHPLC but no
      mutation was observed by direct sequencing. In addition, K-RAS mutation was
      detected in 2 out of 127 (1.6%) patients by direct sequencing. CONCLUSIONS: The
      incidence of EGFR mutations was relatively high using DHPLC method but no
      mutation with direct sequencing in Chinese ESCC patients.

PMID- 24103529
TI  - Outcome measures in rheumatoid arthritis randomised trials over the last 50
      years.
AB  - BACKGROUND: The development and application of standardised sets of outcomes to
      be measured and reported in clinical trials have the potential to increase the
      efficiency and value of research. One of the most notable of the current outcome
      sets began nearly 20 years ago: the World Health Organization and International
      League of Associations for Rheumatology core set of outcomes for rheumatoid
      arthritis clinical trials, originating from the OMERACT (Outcome Measures in
      Rheumatology) Initiative. This study assesses the use of this core outcome set by
      randomised trials in rheumatology. METHODS: An observational review was carried
      out of 350 randomised trials for the treatment of rheumatoid arthritis identified
      through The Cochrane Library (up to and including September 2012 issue). Reports
      of these trials were evaluated to determine whether or not there were trends in
      the proportion of trials reporting on the full set of core outcomes over time.
      Researchers who conducted trials after the publication of the core set were
      contacted to assess their awareness of it and to collect reasons for non
      inclusion of the full core set of outcomes in the study. RESULTS: Since the
      introduction of the core set of outcomes for rheumatoid arthritis, the
      consistency of measurement of the core set of outcomes has improved, although
      variation in the choice of measurement instrument remains. The majority of
      trialists who responded said that they would consider using the core outcome set
      in the design of a new trial. CONCLUSIONS: This observational review suggests
      that a higher percentage of trialists conducting trials in rheumatoid arthritis
      are now measuring the rheumatoid arthritis core outcome set. Core outcome sets
      have the potential to improve the evidence base for health care, but
      consideration must be given to the methods for disseminating their availability
      amongst the relevant communities.

PMID- 24103530
TI  - Objective Structured Assessment of Technical Skills (OSATS) evaluation of
      theoretical versus hands-on training of vaginal breech delivery management: a
      randomized trial.
AB  - OBJECTIVE: To compare the skills of performing a vaginal breech (VB) delivery
      after hands-on training versus demonstration. STUDY DESIGN: We randomized medical
      students to a 30-min demonstration (group 1) or a 30-min hands-on (group 2)
      training session using a standardized VB management algorithm on a pelvic
      training model. Subjects were tested with a 25 item Objective Structured
      Assessment of Technical Skills (OSATS) scoring system immediately after training
      and 72 h thereafter. OSATS scores were the primary outcome. Performance time
      (PT), self assessment (SA), confidence (CON), and global rating scale (GRS) were
      the secondary outcomes. Statistics were performed using the Mann-Whitney U-test,
      chi-square test, and multiple linear regression analysis. RESULTS: 172 subjects
      were randomized. OSATS scores (primary outcome) were significantly higher in
      group 2 (n=88) compared to group 1 (n=84) (21.18+/-2.29 vs. 20.19+/-2.37,
      respectively; p=0.006). The secondary outcomes GRS (10.31+/-2.28 vs. 9.17+/-2.21;
      p=0.001), PT (214.60+/-57.97 s vs. 246.98+/-59.34 s; p<0.0001), and CON (3.14+/
      0.89 vs. 2.85+/-0.90; p=0.04) were also significantly different between groups,
      favoring group 2. After 72 h, primary and secondary outcomes were not
      significantly different between groups. In a multiple linear regression analysis,
      group assignment (odds ratio [OR] 1.60; 95% confidence interval [CI] 1.14-2.05;
      p<0.0001) and gender (OR 2.91; 95% CI 2.45-3.38; p<0.0001) independently
      influenced OSATS scores. CONCLUSION: Hands-on training leads to a significant
      improvement of VB management in a pelvic training model, but this effect was only
      seen in the short term.

PMID- 24103531
TI  - A comparison of three different entry techniques in gynecological laparoscopic
      surgery: a randomized prospective trial.
AB  - OBJECTIVE: Laparoscopic entry techniques vary and still remain debated. We
      conducted a randomized control trial to compare three entry techniques. STUDY
      DESIGN: Women aged 18-70 years, nominated for laparoscopic surgery at University
      of Rome Campus Bio-Medico, were randomized into three different groups: Veress
      needle (VER), Direct trocar insertion (DIR) and Open technique (OP). For each
      group, minor complications (extra-peritoneal insufflation, trocar site bleeding,
      omental injury and surgical site infection), failed entry and time of entry of
      the main trocar were evaluated. Major complications were also considered. Between
      group comparisons were performed using chi-square test. Significance P value was
      <0.05. RESULTS: A series of 595 consecutive procedures were included: 193 in the
      VER group, 187 in the DIR group and 215 in the OP group. Minor complications
      occurred in 36 cases: extraperitoneal insufflation (n=6) in the VER group only,
      site bleeding (n=2 in the VER group, n=2 in the DIR group and n=1 in the OP
      group), site infection (n=5 in the VER and n=6 in OP group), and omental injury
      (n=6 in the VER group and n=3 in the DIR group). Failed entry occurred in 4 cases
      of the VER group and 1 case of the DIR group. Mean time of entry was 212.4, 71.4
      and 161.7s for the VER, DIR and OP groups respectively. Among major
      complications, one bowel injury resulted following the Veress technique.
      CONCLUSIONS: In our series, DIR and OP entry presented a lower risk of minor
      complications compared with VER. In addition, time of entry was shorter in DIR
      than with OP entry.

PMID- 24103532
TI  - Intracytoplasmic morphologically selected sperm injection is beneficial in cases
      of advanced maternal age: a prospective randomized study.
AB  - OBJECTIVE: To evaluate advanced maternal age as a rationale for performing
      intracytoplasmic morphologically selected sperm injection (IMSI). STUDY DESIGN:
      This study included couples undergoing intracytoplasmic sperm injection (ICSI) as
      a result of advanced maternal age (>=37 years old). Sample size calculations were
      based on the assumption that a 15% difference in implantation rate would mean a
      clinically significant difference. To achieve this difference, 33 cycles would be
      needed in each treatment arm (with a significance level of 5% and power of 85%).
      Couples were randomly allocated to one of two sperm selection procedures (ICSI,
      n=33; or IMSI, n=33). Sperm selection in the ICSI group was analyzed under a
      magnification of 400*. Sperm selection in the IMSI group was analyzed under high
      magnification of 6600*. The groups were compared with regard to the outcome of
      the cycles. RESULTS: IMSI cycles showed significantly higher implantation (4/33,
      12.1% vs. 18/47, 38.3%, p=0.026) and pregnancy (4/29, 13.8 vs. 18/30, 60.0%,
      p<0.001) rates. The IMSI procedure positively influenced the blastocyst formation
      rate (RC: 15.00, R2: 49.9%, p=0.001) and implantation rate (RC: 24.04, R2: 9.6,
      p=0.027), and was determinant to the increased odds of pregnancy (OR: 9.0, CI:
      2.17-37.38, p=0.001). CONCLUSION: It seems that the injection of a
      morphologically normal spermatozoon overcomes the low oocyte quality in older
      women, resulting in improved embryo quality and in a 9-fold increase in the
      clinical pregnancy rate in couples with advanced maternal age.

PMID- 24103533
TI  - Role of the aromatase inhibitor letrozole in the management of uterine leiomyomas
      in premenopausal women.
AB  - BACKGROUND: Uterine myomas are benign tumours affecting 20-40% women. Various
      medical and surgical therapeutic options are available but the search for an
      ideal medical option continues. Aromatase inhibitors have recently been reported
      to have a potential role in the management of oestrogen-dependent conditions like
      endometriosis and leiomyoma. OBJECTIVE: To evaluate the effect of letrozole on
      uterine myoma size and symptomatology in perimenopausal women. STUDY DESIGN:
      Prospective interventional study conducted on 30 premenopausal women aged between
      30 and 55 years with menstrual or pressure symptoms and having a single
      intrauterine myoma of size 4 cm or more with or without one or more additional
      myomata each of size 2 cm or less. They received tablet letrozole 2.5 mg a day
      for 12 weeks, and the effect of the drug on myoma size and volume and
      symptomatology was studied along with the adverse effect profile and patient
      satisfaction. RESULTS: The mean myoma size reduced from 5.4+/-1.3 cm to 4.3+/-0.9
      cm (p<0.05) and the myoma volume exhibited a reduction of 52.45% (p=0.00) at the
      end of 3 months. The symptomatology score showed a significant improvement that
      persisted up to 3 months after cessation of therapy. No significant effect was
      observed on lipid profile, serum estradiol, progesterone, testosterone and FSH
      and LH levels during the therapy. Nausea and hot flushes were the main adverse
      effects observed and were self-limiting. CONCLUSION: Letrozole significantly
      reduces myoma size and volume and also improves the associated symptoms. It has a
      good adverse effect profile and appears to be a promising medical option for
      management of uterine myomas.

PMID- 24103534
TI  - Messenger RNA levels of podocyte-associated proteins in subjects with different
      degrees of glucose tolerance with or without nephropathy.
AB  - BACKGROUND: To investigate gene expression of podocyte-specific proteins in urine
      of diabetes and prediabetes subjects and the association of these proteins with
      albuminuria. METHODS: Fifteen controls, 19 prediabetes, and 67 diabetes subjects
      were included. Messenger RNA of nephrin, podocin, podocalyxin, synaptopodin,
      TRPC6, alpha-actinin-4, and TGF-beta1 were measured using RT-PCR. Podocyte marker
      expression was correlated with albuminuria, glycemic control, and renal function.
      The diagnostic performance of the genes used to detect increased albuminuria was
      assessed using ROC curves and Poisson regressions. RESULTS: Podocyte marker
      expression was significantly higher in diabetic subjects. Urinary nephrin was
      correlated with increasing levels of albuminuria; risk of albuminuria increased
      by 20% for every one-unit increase in the log10 of nephrin mRNA. Nephrinuria was
      found in 53%, 71%, and 90% of normo-, micro-, and macroalbuminuric diabetes
      subjects, respectively (p = 0.023). Urinary nephrin, podocalyxin, TRPC6, podocin,
      and alpha actinin-4 were correlated with glycemic control and albuminuria but not
      with renal function. CONCLUSIONS: Diabetes subjects had higher urinary mRNA
      levels of podocyte proteins than nondiabetic subjects, even the normoalbuminuric
      patients. Nephrinuria was correlated with diabetic nephrophathy stage and
      predicted pathological albuminuria. Urinary mRNA levels of podocyte markers of
      prediabetic subjects did not differ from controls.

PMID- 24103535
TI  - Reliability of lower limb motor evoked potentials in stroke and healthy
      populations: how many responses are needed?
AB  - OBJECTIVE: To determine the intra- and inter-session reliability of motor evoked
      potential (MEP) size parameters in the lower limb of patients with stroke,
      focussing on the number of MEPs collected and the method of measuring MEP size.
      METHODS: Transcranial magnetic stimulation was used to elicit MEPs in the soleus
      muscle of patients with stroke (n=13) and age-matched healthy participants (n=13)
      during low level muscle activation. Two sets of 10 responses were collected in
      the first session and a further 10 responses collected in a second session held 7
      days later. Four MEP size measurements were made using 4, 6, 8, or all 10 of the
      MEPs collected. Intra- and inter-session reliability was examined using
      intraclass correlation coefficients (ICC) and typical percentage error. RESULTS:
      Intrasession ICC statistics using 6 or more MEPs were >0.85 in the stroke group
      but intersession values were all <0.5. Reliability was best when measuring
      parameters from individual MEPs rather than averaged responses. CONCLUSIONS:
      Reliability of intrasession MEP size is excellent in the lower limb of patients
      with stroke using as few as 6 MEPs but intersession reliability is poor.
      SIGNIFICANCE: Comparing MEP size measures across two or more sessions is
      questionable in the lower limb of patients with stroke.

PMID- 24103536
TI  - Re-thinking resuscitation goals: an alternative point of view!

PMID- 24103537
TI  - Aircraft noise and cardiovascular disease near Heathrow airport in London: small
      area study.
AB  - OBJECTIVE: To investigate the association of aircraft noise with risk of stroke,
      coronary heart disease, and cardiovascular disease in the general population.
      DESIGN: Small area study. SETTING: 12 London boroughs and nine districts west of
      London exposed to aircraft noise related to Heathrow airport in London.
      POPULATION: About 3.6 million residents living near Heathrow airport. Risks for
      hospital admissions were assessed in 12 110 census output areas (average
      population about 300 inhabitants) and risks for mortality in 2378 super output
      areas (about 1500 inhabitants). MAIN OUTCOME MEASURES: Risk of hospital
      admissions for, and mortality from, stroke, coronary heart disease, and
      cardiovascular disease, 2001-05. RESULTS: Hospital admissions showed
      statistically significant linear trends (P<0.001 to P<0.05) of increasing risk
      with higher levels of both daytime (average A weighted equivalent noise 7 am to
      11 pm, L(Aeq),16 h) and night time (11 pm to 7 am, Lnight) aircraft noise. When
      areas experiencing the highest levels of daytime aircraft noise were compared
      with those experiencing the lowest levels (>63 dB v <= 51 dB), the relative risk
      of hospital admissions for stroke was 1.24 (95% confidence interval 1.08 to
      1.43), for coronary heart disease was 1.21 (1.12 to 1.31), and for cardiovascular
      disease was 1.14 (1.08 to 1.20) adjusted for age, sex, ethnicity, deprivation,
      and a smoking proxy (lung cancer mortality) using a Poisson regression model
      including a random effect term to account for residual heterogeneity.
      Corresponding relative risks for mortality were of similar magnitude, although
      with wider confidence limits. Admissions for coronary heart disease and
      cardiovascular disease were particularly affected by adjustment for South Asian
      ethnicity, which needs to be considered in interpretation. All results were
      robust to adjustment for particulate matter (PM10) air pollution, and road
      traffic noise, possible for London boroughs (population about 2.6 million). We
      could not distinguish between the effects of daytime or night time noise as these
      measures were highly correlated. CONCLUSION: High levels of aircraft noise were
      associated with increased risks of stroke, coronary heart disease, and
      cardiovascular disease for both hospital admissions and mortality in areas near
      Heathrow airport in London. As well as the possibility of causal associations,
      alternative explanations such as residual confounding and potential for
      ecological bias should be considered.

PMID- 24103539
TI  - Airport noise and cardiovascular disease.

PMID- 24103538
TI  - Residential exposure to aircraft noise and hospital admissions for cardiovascular
      diseases: multi-airport retrospective study.
AB  - OBJECTIVE: To investigate whether exposure to aircraft noise increases the risk
      of hospitalization for cardiovascular diseases in older people (>= 65 years)
      residing near airports. DESIGN: Multi-airport retrospective study of
      approximately 6 million older people residing near airports in the United States.
      We superimposed contours of aircraft noise levels (in decibels, dB) for 89
      airports for 2009 provided by the US Federal Aviation Administration on census
      block resolution population data to construct two exposure metrics applicable to
      zip code resolution health insurance data: population weighted noise within each
      zip code, and 90th centile of noise among populated census blocks within each zip
      code. SETTING: 2218 zip codes surrounding 89 airports in the contiguous states.
      PARTICIPANTS: 6 027 363 people eligible to participate in the national medical
      insurance (Medicare) program (aged >= 65 years) residing near airports in 2009.
      MAIN OUTCOME MEASURES: Percentage increase in the hospitalization admission rate
      for cardiovascular disease associated with a 10 dB increase in aircraft noise,
      for each airport and on average across airports adjusted by individual level
      characteristics (age, sex, race), zip code level socioeconomic status and
      demographics, zip code level air pollution (fine particulate matter and ozone),
      and roadway density. RESULTS: Averaged across all airports and using the 90th
      centile noise exposure metric, a zip code with 10 dB higher noise exposure had a
      3.5% higher (95% confidence interval 0.2% to 7.0%) cardiovascular hospital
      admission rate, after controlling for covariates. CONCLUSIONS: Despite
      limitations related to potential misclassification of exposure, we found a
      statistically significant association between exposure to aircraft noise and risk
      of hospitalization for cardiovascular diseases among older people living near
      airports.

PMID- 24103540
TI  - New polyps, old tricks: controversy about removing benign bowel lesions.

PMID- 24103541
TI  - Why do we need nongenomic glucocorticoid mechanisms?
AB  - Glucocorticoids (GCs) are a class of steroid hormones that have been known to be
      involved in various physiological processes and to play a pivotal role in
      preserving basal and stress-related homeostasis. GCs are also widely used
      clinically as anti-inflammatory, immunosuppressive, anti-shock drugs. It is
      believed traditionally that GCs exert most of their effects genomically. In
      addition to the well-known classical genomic mechanisms, GCs also affect various
      functions via rapid, nongenomic mechanisms. The therapeutic benefits of
      nongenomic GC actions have been exploited in clinical medicine, especially with
      high-dose pulsed glucocorticoid administration. However, it is certainly not the
      case that the inherent nongenomic glucocorticoid mechanisms evolved only for
      their clinical utility. Here, we review the recent literature on nongenomic
      actions of GCs related to stress and the physiological significance of these
      actions, and we propose reasons why nongenomic mechanisms of GC actions are
      needed. 

PMID- 24103542
TI  - High-throughput genotyping system as a robust and useful tool in oncology:
      experience from a single institution.
AB  - BACKGROUND AND AIM: Single nucleotide polymorphisms (SNPs) are substitutions of
      one base for another in the gene sequence and conforms the basis for
      pharmacogenetics and the development of personalized medicine. Many methods have
      been developed for SNP genotyping. The aim of the present study was to validate
      the use of a novel high-throughput genotyping system. METHODS: Five SNPs
      (rs25487, rs25489, rs1799782, rs13181, and rs11615) were genotyped in 118 cancer
      patients using the classical method PCR restriction fragment length polymorphism
      (RFLP) and the high-throughput, automated assay Biotrove OpenArray((r)) NT
      Cycler, trying to explore the feasibility and reproducibility of the OpenArray
      system in the context of oncology. RESULTS: The call rates obtained ranged from
      95.7 to 100% for both techniques. The percentage of overlapping ranged from 96.2
      to 100% among both assays, showing a high reproducibility between the techniques.
      CONCLUSION: These findings, together with the low-cost and the simple and fast
      work flow, suggest that the OpenArray system is a robust and easy methodology for
      genotyping in the field of oncology.

PMID- 24103543
TI  - Systematic review of changes in maxillary incisor exposure and upper lip position
      with Le Fort I type osteotomies with or without cinch sutures and/or VY closures.
AB  - The aim was to systematically review the maxillary incisor exposure and upper lip
      position changes with Le Fort I type osteotomies for advancement +/- impaction
      with rigid internal fixation, taking into account the use of cinch sutures and VY
      closures. Electronic databases (Cochrane Library, Medline, Embase, and Web of
      Science) were searched using medical subject headings (MeSH), key words,
      truncations, and Boolean operators. Hand searching was also undertaken. Of 979
      articles identified, 15 were included (11 retrospective, two prospective, and two
      unspecified). Relevant study details and outcomes were recorded on a spreadsheet,
      along with an assessment of their quality. In total, these studies assessed 419
      patients (266 female, 118 male) with a mean age of 26.4 years (range 14-57
      years). Soft tissue changes were assessed on lateral cephalometric radiographs.
      The mean maxillary hard tissue advancement and impaction ranged between 0.94 and
      8.77 mm and -0.56 and 4.2 mm, respectively. The ranges of ratios demonstrated
      that from pronasale (0.24-0.35) to labrale superius (0.36-1.43), the soft tissues
      followed the underlying horizontal hard tissue movement increasingly more
      closely. Alar base cinch sutures and VY closures tended to increase these ratios.
      The soft tissue response was more variable vertically. None of the studies
      reported on maxillary incisor exposure change. More good quality prospective
      studies are needed.

PMID- 24103544
TI  - Postoperative radiotherapy after radical prostatectomy: let's work together to
      tackle the known unknowns.

PMID- 24103545
TI  - On endothelial cells and aneurysms.

PMID- 24103546
TI  - Burr holes for Moyamoya.

PMID- 24103547
TI  - Risk-stratification of ischemic stroke patients on the basis of anatomic criteria
      essential to the prevention of hospital-acquired conditions and performance along
      patient safety indicators.

PMID- 24103548
TI  - Lipomatosis of nerve.

PMID- 24103549
TI  - Research productivity and fellowship training in neurosurgery.

PMID- 24103550
TI  - Lateral canthotomy: part of a neurosurgeon's toolkit?

PMID- 24103551
TI  - Effect of storage and preservation of milk samples on the response of microbial
      inhibitor tests.
AB  - The aim of this study was to evaluate the effect of storage time (4  degrees C)
      on milk samples and the use of azidiol as preservative on the results of
      microbial inhibitor tests used to detect antimicrobials in milk. For this
      purpose, 16 milk bulk samples divided into two aliquots, preservative-free and
      with azidiol, spiked with 12 concentrations of amoxicillin, ampicillin,
      penicillin G and oxytetracycline, were used. The milk samples were analysed using
      the BRT MRL, Delvotest MCS Accelerator and Eclipse 100 at 0, 24, 48 and 72 h
      stored at 4  degrees C. The logistic regression model was applied to study the
      effect of storage time (ST), preservative (P) and their interaction (ST*P). At a
      concentration equivalent to the Detection Limit (DL), the positive results of
      microbial inhibitor tests do not remain stable during storage time. These results
      are more reproducible if samples are stored with a preservative. At Maximum
      Residue Limits (MRLs) concentration microbial inhibitor tests can detect
      penicillin for up to 72 h of storage. For oxytetracycline, the BRT MRL and
      Delvotest MCS tests presents DL exceeding the MRL, therefore they are not
      sensitivity to this tetracycline (0% positive results). By contrast Eclipse 100,
      whose DL is lower than the MRL, gave 100% positive results during the 72 h
      storage period. It can be concluded that it would be convenient to store milk
      samples with azidiol at 4  degrees C and to carry out analyses within the first
      48 h since milk sampling. 

PMID- 24103552
TI  - International test results for objective lens quality, resolution, spectral
      accuracy and spectral separation for confocal laser scanning microscopes.
AB  - As part of an ongoing effort to increase image reproducibility and fidelity in
      addition to improving cross-instrument consistency, we have proposed using four
      separate instrument quality tests to augment the ones we have previously
      reported. These four tests assessed the following areas: (1) objective lens
      quality, (2) resolution, (3) accuracy of the wavelength information from spectral
      detectors, and (4) the accuracy and quality of spectral separation algorithms.
      Data were received from 55 laboratories located in 18 countries. The largest
      source of errors across all tests was user error which could be subdivided
      between failure to follow provided protocols and improper use of the microscope.
      This truly emphasizes the importance of proper rigorous training and diligence in
      performing confocal microscopy experiments and equipment evaluations. It should
      be noted that there was no discernible difference in quality between confocal
      microscope manufactures. These tests, as well as others previously reported, will
      help assess the quality of confocal microscopy equipment and will provide a means
      to track equipment performance over time. From 62 to 97% of the data sets sent in
      passed the various tests demonstrating the usefulness and appropriateness of
      these tests as part of a larger performance testing regiment. 

PMID- 24103553
TI  - Continuous glucose sensors for glycaemic control in the ICU: have we arrived?
AB  - Dr Blixt and colleagues show in an elegant pilot study that the continuous
      measurement of glucose in venous blood by microdialysis in a central venous
      catheter is feasible in critically ill patients. The performance of this type of
      continuous glucose monitoring device equals the performance of the commonly used
      handheld blood glucose meters. But are we, as ICU physicians and nurses, now
      ready to implement such continuous blood glucose sensors into the daily practice
      of the ICU? The only yardstick to this is "are these devices truly helping us
      ...in our critically ill patients". 

PMID- 24103555
TI  - Decidual natural killer cell interactions with trophoblasts are impaired in
      pregnancies at increased risk of preeclampsia.
AB  - Transformation of the uterine spiral arteries (SAs) during pregnancy is critical
      to support the developing fetus, and is impaired in some pregnancy disorders,
      including preeclampsia. Decidual natural killer (dNK) cells play a role in SA
      remodeling, although their interactions with fetal trophoblast remain unclear. A
      uterine artery Doppler resistance index (RI) in the first trimester of pregnancy
      can be used as a proxy measure of the extent of SA remodeling; we have used this
      technique to characterize dNK cells from pregnancies with normal (normal RI) and
      impaired (high RI) SA remodeling, which display least and highest risk of
      developing preeclampsia, respectively. We examined the impact of dNK cell
      secreted factors on trophoblast motility, chemoattraction, and signaling pathways
      to determine the contribution of dNK cells to SA transformation. We demonstrated
      that the chemoattraction of the trophoblast by dNK cells is impaired in
      pregnancies with high RI, as is the ability to induce trophoblast outgrowth from
      placental villous explants. These processes are dependent on activation of the
      extracellular signal-regulated kinase 1/2 and phosphatidylinositol 3-kinase-Akt
      signaling pathways, which were altered in trophoblasts incubated with secreted
      factors from dNK cells from high RI pregnancies. Therefore, by characterizing
      pregnancies using uterine artery Doppler RI before dNK cell isolation, we have
      identified that impaired dNK-trophoblast interactions may lead to poor
      placentation. These findings have implications for pregnancy pathological
      conditions, such as preeclampsia.

PMID- 24103554
TI  - A review of the serotonin transporter and prenatal cortisol in the development of
      autism spectrum disorders.
AB  - The diagnosis of autism spectrum disorder (ASD) during early childhood has a
      profound effect not only on young children but on their families. Aside from the
      physical and behavioural issues that need to be dealt with, there are significant
      emotional and financial costs associated with living with someone diagnosed with
      ASD. Understanding how autism occurs will assist in preparing families to deal
      with ASD, if not preventing or lessening its occurrence.Serotonin plays a vital
      role in the development of the brain during the prenatal and postnatal periods,
      yet very little is known about the serotonergic systems that affect children with
      ASD. This review seeks to provide an understanding of the biochemistry and
      physiological actions of serotonin and its termination of action through the
      serotonin reuptake transporter (SERT). Epidemiological studies investigating
      prenatal conditions that can increase the risk of ASD describe a number of
      factors which elevate plasma cortisol levels causing such symptoms during
      pregnancy such as hypertension, gestational diabetes and depression. Because
      cortisol plays an important role in driving dysregulation of serotonergic
      signalling through elevating SERT production in the developing brain, it is also
      necessary to investigate the physiological functions of cortisol, its action
      during gestation and metabolic syndromes. 

PMID- 24103557
TI  - ICAM-1 deficiency exacerbates sarcoid-like granulomatosis induced by
      Propionibacterium acnes through impaired IL-10 production by regulatory T cells.
AB  - Propionibacterium acnes has been implicated as one of the suggested causative
      antigens for sarcoidosis, a systemic granulomatous disease. By injecting heat
      killed P. acnes into the dorsal skin of C57BL/6J mice on days 1, 3, 5, and 14,
      sarcoid-like granulomatosis was induced in skin and lungs of these mice on day
      28. To clarify the role of cell adhesion molecules in cutaneous sarcoidosis, we
      induced sarcoid-like granulomatosis in mice deficient of intercellular adhesion
      molecule (ICAM)-1, L-selectin, P-selectin, or E-selectin via repeated P. acnes
      injection. Histopathologic analysis revealed that granuloma formation was
      aggravated in the skin and lungs of ICAM-1-deficient mice compared with wild-type
      mice. Within skin granulomas of ICAM-1-deficient mice, P. acnes immunization up
      regulated mRNA expression of tumor necrosis factor-alpha, although it failed to
      induce IL-10 mRNA expression in contrast to wild-type mice. Infiltration of
      regulatory T cells into skin granuloma was similar between wild-type mice and
      ICAM-1-deficient mice. P. acnes immunization induced IL-10 production by
      CD4(+)CD25(+)Foxp3(+) regulatory T cells in lymph nodes of wild-type mice in
      vivo, which was absent in regulatory T cells of ICAM-1-deficient mice. Our
      results indicate that ICAM-1 is imperative for inducing regulatory T cells to
      produce IL-10 in vivo, which would prevent granuloma formation.

PMID- 24103556
TI  - Canonical transforming growth factor-beta signaling regulates disintegrin
      metalloprotease expression in experimental renal fibrosis via miR-29.
AB  - Fibrosis pathophysiology is critically regulated by Smad 2- and Smad 3-mediated
      transforming growth factor-beta (TGF-beta) signaling. Disintegrin
      metalloproteases (Adam) can manipulate the signaling environment, however, the
      role and regulation of ADAMs in renal fibrosis remain unclear. TGF-beta
      stimulation of renal cells results in a significant up-regulation of Adams 10,
      17, 12, and 19. The selective Smad2/3 inhibitor SB 525334 reversed these TGF-beta
      induced changes. In vivo, using ureteral obstruction to model renal fibrosis, we
      observed increased Adams gene expression that was blocked by oral administration
      of SB 525334. Similar increases in Adam gene expression also occurred in
      preclinical models of hypertension-induced renal damage and glomerulonephritis.
      miRNAs are a recently discovered second level of regulation of gene expression.
      Analysis of 3' untranslated regions of Adam12 and Adam19 mRNAs showed multiple
      binding sites for miR-29a, miR-29b, and miR-29c. We show that miR-29 family
      expression is decreased after unilateral ureter obstruction and this significant
      decrease in miR-29 family expression was observed consistently in preclinical
      models of renal dysfunction and correlated with an increase in Adam12 and Adam19
      expression. Exogenous overexpression of the miR-29 family blocked TGF-beta
      mediated up-regulation of Adam12 and Adam19 gene expression. This study shows
      that Adams are involved in renal fibrosis and are regulated by canonical TGF-beta
      signaling and miR-29. Therefore, both Adams and the miR-29 family represent
      therapeutic targets for renal fibrosis.

PMID- 24103558
TI  - High school dropout and long-term sickness and disability in young adulthood: a
      prospective propensity score stratified cohort study (the Young-HUNT study).
AB  - BACKGROUND: High school dropout and long-term sickness absence/disability pension
      in young adulthood are strongly associated. We investigated whether common risk
      factors in adolescence may confound this association. METHODS: Data from 6612
      school-attending adolescents (13-20 years old) participating in the Norwegian
      Young-HUNT1 Survey (1995-1997) was linked to long-term sickness absence or
      disability pension from age 24-29 years old, recorded in the Norwegian Labour and
      Welfare Organisation registers (1998-2008). We used logistic regression to
      estimate risk differences of sickness or disability for school dropouts versus
      completers, adjusting for health, health-related behaviours, psychosocial
      factors, school problems, and parental socioeconomic position. In addition, we
      stratified the regression models of sickness and disability following dropout
      across the quintiles of the propensity score for high school dropout. RESULTS:
      The crude absolute risk difference for long-term sickness or disability for a
      school dropout compared to a completer was 0.21% or 21% points (95% confidence
      interval (CI), 17 to 24). The adjusted risk difference was reduced to 15% points
      (95% CI, 12 to 19). Overall, high school dropout increased the risk for sickness
      or disability regardless of the risk factor level present for high school
      dropout. CONCLUSION: High school dropouts have a strongly increased risk for
      sickness and disability in young adulthood across all quintiles of the propensity
      score for dropout, i.e. independent of own health, family and socioeconomic
      factors in adolescence. These findings reveal the importance of early prevention
      of dropout where possible, combined with increased attention to labour market
      integration and targeted support for those who fail to complete school.

PMID- 24103559
TI  - Effect of breed on the expression of Sirtuins (Sirt1-7) and antioxidant capacity
      in porcine brain.
AB  - Sirtuins, NAD-dependent histone deacetylase (HDAC), are correlated to aging and
      antioxidant. The aim of this study was to determine breed differences of porcine
      Sirtuins expression and antioxidant capacity in brain between Jinhua pigs (a
      fatty breed of China) and Danish Landrace pigs (a leaner breed). Effect of age on
      Sirtuins' expression was also investigated. At the age of 180 days, the mRNA
      levels of Sirt1, as well as Sirt2 and Sirt4, in Jinhua pigs were greater, but the
      mRNA levels of Sirt3, Sirt5, Sirt6, and Sirt7 of Jinhua pigs were lower compared
      with Danish Landrace pigs. Likewise, at the same BW of 64 kg, the mRNA levels of
      Sirtuins, except Sirt5 and Sirt7, in Jinhua pigs were greater than Danish
      Landrace pigs. Meanwhile, Jinhua pigs possessed higher antioxidants activity than
      Danish Landrace pigs either at the same age or at the same BW. Furthermore, mRNA
      levels of Sirtuins were decreased with age in brain of the two breeds from 30 to
      120 days. The results indicated that Sirtuins expression in brain was different
      between fatty and lean pigs, and Sirtuins expression may be correlated to
      antioxidant capacity. In addition, age could down-regulate Siruins expression in
      porcine brain. 

PMID- 24103560
TI  - Costs of providing food assistance to HIV/AIDS patients in Sofala province,
      Mozambique: a retrospective analysis.
AB  - BACKGROUND: As care and antiretroviral treatment (ART) for people living with
      HIV/AIDS become widely available, the number of people accessing these resources
      also increases. Despite this exceptional progress, the estimated coverage in low-
      and middle-income countries is still less than half of all people who need
      treatment. In addition, treatment discontinuation and non-adherence are still
      concerns for ART programs. Governments and partner institutions have sought to
      implement a variety of interventions addressing the main reasons behind the low
      coverage of, discontinuation of, and non-adherence to ART. Food assistance is one
      of those interventions; increasing evidence suggests that this type of
      intervention has the potential to improve ART outcomes. However, to our
      knowledge, no study has estimated its costs in detail. The objective of this
      study was to assess the costs of a program providing food assistance to HIV/AIDS
      patients in Sofala province, Mozambique, in 2009. METHODS: We performed a
      retrospective analysis of the costs of providing food assistance, based on
      financial and economic costs. We used the ingredients approach to estimate costs,
      which involved multiplying the total estimated quantities of goods and services
      actually employed in providing the intervention by their respective unit prices.
      RESULTS: In 2009, the cost of providing food assistance to HIV/AIDS patients was
      $2.27 million, with capital and recurrent costs accounting for 1% and 99% of
      total costs, respectively. Food made up the largest component, at 49% of total
      costs. At 24%, transport operating costs were the second largest item. The cost
      per patient served was $288 over 3 months. CONCLUSION: The food distribution
      program carries significant costs. To assess whether it provides value for money,
      the present study results should be interpreted in conjunction with the program's
      impact, and in comparison with other programs that aim to improve adherence to
      ART. Our costing analysis revealed important management information, indicating
      that the program incurred relatively large overhead costs. This result raises
      questions regarding the efficiency of implementing this food distribution
      program.

PMID- 24103562
TI  - Undernutrition affects embryo quality of superovulated ewes.
AB  - To determine the effect of undernutrition on embryo production and quality in
      superovulated sheep, 45 ewes were allocated into two groups to be fed diets that
      provided 1.5 (control, C; n = 20) or 0.5 (low nutrition, L; n = 25) times daily
      requirements for maintenance, from oestrous synchronization with intravaginal
      sponges to embryo collection. Embryos were collected 7 days after the onset of
      oestrus (day 0). Low nutrition resulted in lower live weight and body condition
      at embryo collection (P < 0.05). Diet (P < 0.01) and day of sampling (P < 0.001)
      significantly affected plasma non-esterified fatty acid (NEFA) and insulin
      concentrations. Plasma leptin concentrations decreased on day 7 only in L ewes. A
      significant effect of dietary treatment (P < 0.05) and day (P < 0.0001) was
      observed on plasma insulin-like growth factor (IGF)-I concentrations. The number
      of recovered oocytes and embryos did not differ between the groups (L: 15.4 +/-
      0.4; C: 12.4 +/- 0.4). Recovery rate was lower (P < 0.05) in the L (60%) than in
      the C group (73%). The total number of embryos and number of viable-transferable
      embryos (5.0 +/- 0.3 and 3.4 +/- 0.3 embryos, respectively) of the L group were
      lower (P < 0.1) when compared with controls (8.4 +/- 0.4 and 6.2 +/- 0.4 embryos,
      respectively). Undernutrition during the period of superovulation and early
      embryonic development reduced total and viable number of embryos. These effects
      might be mediated by disruption of endocrine homeostasis, oviduct environment
      and/or oocyte quality.

PMID- 24103561
TI  - Cardiovascular risk and mortality in end-stage renal disease patients undergoing
      dialysis: sleep study, pulmonary function, respiratory mechanics, upper airway
      collapsibility, autonomic nervous activity, depression, anxiety, stress and
      quality of life: a prospective, double blind, randomized controlled clinical
      trial.
AB  - BACKGROUND: Chronic kidney disease (CKD) is one of the most serious public health
      problems. The increasing prevalence of CKD in developed and developing countries
      has led to a global epidemic. The hypothesis proposed is that patients undergoing
      dialysis would experience a marked negative influence on physiological variables
      of sleep and autonomic nervous system activity, compromising quality of life.
      METHODS/DESIGN: A prospective, consecutive, double blind, randomized controlled
      clinical trial is proposed to address the effect of dialysis on sleep, pulmonary
      function, respiratory mechanics, upper airway collapsibility, autonomic nervous
      activity, depression, anxiety, stress and quality of life in patients with CKD.
      The measurement protocol will include body weight (kg); height (cm); body mass
      index calculated as weight/height(2); circumferences (cm) of the neck, waist, and
      hip; heart and respiratory rates; blood pressures; Mallampati index; tonsil
      index; heart rate variability; maximum ventilatory pressures; negative expiratory
      pressure test, and polysomnography (sleep study), as well as the administration
      of specific questionnaires addressing sleep apnea, excessive daytime sleepiness,
      depression, anxiety, stress, and quality of life. DISCUSSION: CKD is a major
      public health problem worldwide, and its incidence has increased in part by the
      increased life expectancy and increasing number of cases of diabetes mellitus and
      hypertension. Sleep disorders are common in patients with renal insufficiency.
      Our hypothesis is that the weather weight gain due to volume overload observed
      during interdialytic period will influence the degree of collapsibility of the
      upper airway due to narrowing and predispose to upper airway occlusion during
      sleep, and to investigate the negative influences of haemodialysis in the
      physiological variables of sleep, and autonomic nervous system, and respiratory
      mechanics and thereby compromise the quality of life of patients. TRIAL
      REGISTRATION: The protocol for this study is registered with the Brazilian
      Registry of Clinical Trials (ReBEC RBR-7yhr4w and World Health Organization under
      Universal Trial Number UTN: U1111-1127-9390
      [http://www.ensaiosclinicos.gov.br/rg/RBR-7yhr4w/]).

PMID- 24103563
TI  - Impact of thulium VapoEnucleation of the prostate on erectile function: a
      prospective analysis of 72 patients at 12-month follow-up.
AB  - OBJECTIVE: To evaluate changes in erectile function after thulium VapoEnucleation
      of the prostate (ThuVEP) for the treatment of benign prostatic obstruction at 12
      month follow-up. MATERIALS AND METHODS: We prospectively evaluated 72 patients
      who underwent ThuVEP between January and July 2011. Preoperative evaluation
      included maximum urinary flow rate (Qmax), international prostate symptom score
      (IPSS), quality of life (QoL), postvoiding residual urine (PVR), and the Erectile
      function domain of the International Index of Erectile Function (IIEF-EF).
      According to preoperative IIEF-EF score, patients were classified into subgroup A
      (IIEF-EF >=19, n = 38) and subgroup B (IIEF-EF <19, n = 34). All complications
      during the perioperative period were noted and classified according to the
      modified Clavien classification system. All patients were reassessed at 12-month
      follow-up by Qmax, IPSS, QoL, PVR, and IIEF-EF score. Patient data were expressed
      as median (interquartile range). RESULTS: Median patient age was 70 (65-73)
      years, and the median prostate volume was 52.5 (39.75-72) mL, respectively. At 12
      month follow-up, IPSS (20 vs 4), QoL (4 vs 1), Qmax (9.7 vs 22.15 mL/s), and PVR
      (100 vs 15 mL) improved significantly in comparison with preoperative assessment
      (P <=.001) without differences between subgroup A and B. A slight but not
      statistically significant increase of the IIEF-EF domain score was reported at 12
      month follow-up (19.5 vs 20), which could be shown in subgroup A (25 vs 26) and B
      (6 vs 8). CONCLUSION: ThuVEP is a safe and effective procedure for the treatment
      of benign prostatic obstruction. At 12-month follow-up, marginal nonsignificant
      erectile function improvement was reported after surgery.

PMID- 24103564
TI  - Building a medical neighborhood in the safety net: an innovative technology
      improves hematuria workups.
AB  - OBJECTIVE: To analyze whether ereferral is associated with decreased time to
      completion of hematuria workup. METHODS: We included 100 individuals referred to
      Olive View-UCLA Medical Center for urologic consultation for hematuria. Half were
      referred before implementation of ereferral, and half were referred after the
      system was implemented. We performed bivariate analysis to assess correlations of
      baseline subject sociodemographic and clinical characteristics with ereferral
      status. We also created a multivariate linear regression model for log days to
      completion of hematuria workup, with ereferral as the main predictor and subject
      sociodemographic and clinical characteristics as covariates. RESULTS: Excluding
      cases with an infectious cause, the mean number of days from urinalysis
      documenting hematuria to completed hematuria workup was 404 days before ereferral
      and 192 days after implementation of ereferral (median 239 vs 170; 2-sample
      median P = .0013). Upper tract imaging was obtained at a median of 76 days after
      initial positive urinalysis in the absence of infection, 122 days before
      ereferral, and 41 days after implementation of ereferral (2-sample median P =
      .1114). In all cases, lower tract evaluation was completed after upper tract
      imaging. Our multivariable model evaluating factors associated with time to
      hematuria workup demonstrated that ereferral use was independently associated
      with shorter time to hematuria workup (P = .006). CONCLUSION: Electronic
      consultations can significantly shorten the time to work-up of hematuria in the
      safety net.

PMID- 24103565
TI  - Endo-PDI is required for TNFalpha-induced angiogenesis.
AB  - Protein disulfide isomerase (PDI) and its homologs are oxidoreductases
      facilitating protein folding in the ER. Endo-PDI (also termed ERp46) is highly
      expressed in endothelial cells. It belongs to the PDI family but its
      physiological function is largely unknown. We studied the role of Endo-PDI in
      endothelial angiogenic responses. Stimulation of human umbilical vein endothelial
      cells (with TNFalpha (10ng/ml) increased ERK1/2 phosphorylation. This effect was
      largely attenuated by Endo-PDI siRNA, whereas JNK and p38 MAP kinase
      phosphorylation was Endo-PDI independent. Similarly, TNFalpha-stimulated NF
      kappaB signaling determined by IkappaBalpha degradation as well as TNFalpha
      induced ICAM expression was unaffected by Endo-PDI siRNA. The action of Endo-PDI
      was not mediated by extracellular thiol exchange or cell surface PDI as
      demonstrated by nonpermeative inhibitors and PDI-neutralizing antibody. Moreover,
      exogenously added PDI failed to restore ERK1/2 activation after Endo-PDI
      knockdown. This suggests that Endo-PDI acts intracellularly potentially by
      maintaining the Ras/Raf/MEK/ERK pathway. Indeed, knockdown of Endo-PDI attenuated
      Ras activation measured by G-LISA and Raf phosphorylation. ERK activation
      influences gene expression by the transcriptional factor AP-1, which controls MMP
      9 and cathepsin B, two proteases required for angiogenesis. TNFalpha-stimulated
      MMP-9 and cathepsin B induction was reduced by silencing of Endo-PDI.
      Accordingly, inhibition of cathepsin B or Endo-PDI siRNA blocked the TNFalpha
      stimulated angiogenic response in the spheroid outgrowth assays. Moreover ex vivo
      tube formation and in vivo Matrigel angiogenesis in response to TNFalpha were
      attenuated by Endo-PDI siRNA. In conclusion, our study establishes Endo-PDI as a
      novel, important mediator of AP-1-driven gene expression and endothelial
      angiogenic function. 

PMID- 24103566
TI  - A risk table to assist health practitioners assess and prevent the onset of
      depression in later life.
AB  - OBJECTIVE: This study aimed to develop a simple risk table of modifiable factors
      prospectively associated with depression in later life that could be used to
      guide the assessment, management and introduction of preventive strategies in
      clinical practice. METHODS: This retrospective cohort study included 4636 men
      aged 65 to 83 years living in the community who denied history of past diagnosis
      or treatment for depression. They self-reported information about their physical
      activity, weight and height, smoking history, alcohol consumption and dietary
      habits, as well as history of hypertension, diabetes, coronary heart disease and
      stroke. We calculated the body mass index (BMI) in kg/m(2). Three to 8 years
      later they were assessed with the Geriatric Depression Scale 15 (GDS-15) and
      those with a total score of 7 or greater were considered to display clinically
      significant symptoms of depression. We used binomial exponentiated log-linked
      general linear models to estimate the risk ratio (RR) and 95% confidence interval
      (95% CI) of incident depression after adjusting for age, education, marital
      status and prevalent medical illnesses. We calculated the probability of
      depression for each individual combination of risk factors and displayed the
      results in a risk table. RESULTS: Two hundred and twenty-nine men (4.5%) showed
      evidence of incident depression 5.7+/-0.9 (mean+/-standard deviation) years
      later. Measured dietary factors showed no association with incident depression.
      The probability of depression was the highest for older men who were underweight,
      overweight or obese, physically inactive, risk drinkers and smokers (12.0%, 95%
      CI=7.0%, 17.1%), and the lowest for those who had all 4 healthy lifestyle
      markers: physically active, normal body mass, non-risk drinking and non-smoking
      (1.6%, 95% CI=0.6%, 2.5%). The probability of incident depression fell between
      these two extremes for different combinations of lifestyle practices. CONCLUSION:
      Four modifiable lifestyle factors can be used in combination to produce a risk
      table that predicts the probability of incident depression over a period of 3 to
      8 years. The risk table is simple, informative and can be easily incorporated
      into clinical practice to guide assessment and risk reduction interventions.

PMID- 24103567
TI  - Prevalence of metabolic syndrome and its influencing factors among the Chinese
      adults: the China Health and Nutrition Survey in 2009.
AB  - OBJECTIVE: We aimed to estimate the up-to-date prevalence of metabolic syndrome
      (MS) and its influencing factors among the Chinese adults. METHODS: Data were
      obtained from the China Health and Nutrition Survey conducted in 2009, which was
      a cross-sectional and partially nationally representative study including a total
      of 7488 Chinese adults (age >=18 years). RESULTS: The overall age-standardized
      prevalence estimates of the MS were 21.3% (95%confidence interval (CI): 20.4%
      22.2%), 18.2% (95%CI: 17.3%-19.1%) and 10.5% (95%CI: 9.8%-11.2%) based on
      definitions of revised NCEP ATPIII, IDF and CDS criteria, respectively.
      Individuals who were women (compared to men: odds ratio [OR]=1.37, 95% CI=1.16
      1.61), 40 years or older (compared to less than 40 years old: OR=2.82, 95%CI=2.37
      3.34 for 40-59 years; OR=4.41, 95%CI=3.68-5.29 for 60 years or older),
      overweight/obese (compared to normal weight: OR=4.32, 95%CI=3.77-4.95 for
      overweight; OR=11.24, 95%CI=9.53-13.26 for obese), and living in urban area
      (compared to living in rural area: OR=1.27, 95%CI=1.12-1.43) were more likely to
      have a higher prevalence estimate of MS. In addition, frequency of alcohol
      consumption and cigarette intake were also found to be significantly associated
      with probability of MS. CONCLUSIONS: Our results suggest an urgent need to
      develop national strategies for the prevention, detection, treatment and control
      of obesity and MS in China.

PMID- 24103568
TI  - Benign cutaneous plexiform hybrid tumor of perineurioma and cellular
      neurothekeoma arising from the nose.
AB  - Very recently, Requena et al. have demonstrated the detailed clinicopathological
      features of 9 cases of a benign cutaneous plexiform nerve sheath tumor with
      hybrid characteristics of perineurioma and cellular neurothekeoma, given the name
      as a benign cutaneous plexiform hybrid tumor of perineurioma and cellular
      neurothekeoma, all of which were peculiarly located on the lips. Herein we
      described the first case of that arising from the nose, but not the lip,
      representing a histological hybridoma of perineurioma and cellular neurothekeoma
      after thorough consideration especially with its immunohistochemical profile. 

PMID- 24103569
TI  - Trends from 1996 to 2007 in incidence and mortality outcomes of heart failure
      after acute myocardial infarction: a population-based study of 20,812 patients
      with first acute myocardial infarction in Western Australia.
AB  - BACKGROUND: Advances in treatment for acute myocardial infarction (AMI) are
      likely to have had a beneficial impact on the incidence of and deaths
      attributable to heart failure (HF) complicating AMI, although limited data are
      available to support this contention. METHODS AND RESULTS: Western Australian
      linked administrative health data were used to identify 20 812 consecutive
      patients, aged 40 to 84 years, without prior HF hospitalized with an index
      (first) AMI between 1996 and 2007. We assessed the temporal incidence of and
      adjusted odds ratio/hazard ratio for death associated with HF concurrent with AMI
      admission and within 1 year after discharge. Concurrent HF comprised 75% of
      incident HF cases. Between the periods 1996-1998 and 2005-2007, the prevalence of
      HF after AMI declined from 28.1% to 16.5%, with an adjusted odds ratio of 0.50
      (95% CI, 0.44 to 0.55). The crude 28-day case-fatality rate for patients with
      concurrent HF declined marginally from 20.5% to 15.9% (P < 0.05) compared with
      those without concurrent HF, in whom the case-fatality rate declined from 11.0%
      to 4.8% (P < 0.001). Concurrent HF was associated with a multivariate-adjusted
      odds ratio of 2.2 for 28-day mortality and a hazard ratio of 2.2 for 1-year
      mortality in 28-day survivors. Occurrence of HF within 90 days of the index AMI
      was associated with an adjusted hazard ratio of 2.7 for 1-year mortality in 90
      day survivors. CONCLUSIONS: Despite encouraging declines in the incidence of HF
      complicating AMI, it remains a common problem with high mortality. Increased
      attention to these high-risk patients is needed given the lack of improvement in
      their long-term prognosis.

PMID- 24103570
TI  - Fluorescent oxidation products and risk of coronary heart disease: a prospective
      study in women.
AB  - BACKGROUND: Oxidative stress is implicated in the etiology of coronary heart
      disease (CHD). New measures to capture oxidative stress are warranted.
      Fluorescent oxidation products (FlOPs) can be measured in plasma and have been
      shown to reflect levels of oxidative stress and to predict risk of CHD in men
      over 6 years of follow-up. The objective of this study is to determine whether
      measures of FlOPs are associated with risk of CHD in women over an extended
      follow-up period. METHODS AND RESULTS: We measured FlOP by spectrofluorometer in
      a nested case-control study within the Nurses' Health Study, with baseline blood
      collection in 1990 and follow-up of 397 incident CHD cases through 2004 matched
      1:2 with controls. Level of FlOPs was independently associated with CHD. The
      relative risk across extreme quintiles was 1.64 (95% confidence interval [CI],
      1.06 to 2.53) when adjusted for lifestyle factors, lipids and C-reactive protein
      (P trend across quintiles = 0.01). A slightly stronger association was observed
      when analyses were restricted to women fasting > 8 hours at blood draw (RR, 1.91;
      95% CI, 1.16 to 3.15). In exploratory time to event analyses, high levels of
      FlOPs measured >= 5 years before the CHD event, but not closer to the CHD event,
      were associated with the risk of CHD. CONCLUSIONS: Higher levels of FlOPs were
      associated with the risk of CHD in women. The association appeared strongest for
      long-term prediction of CHD events.

PMID- 24103571
TI  - Acute inhibition of excessive mitochondrial fission after myocardial infarction
      prevents long-term cardiac dysfunction.
AB  - BACKGROUND: Ischemia and reperfusion (IR) injury remains a major cause of
      morbidity and mortality and multiple molecular and cellular pathways have been
      implicated in this injury. We determined whether acute inhibition of excessive
      mitochondrial fission at the onset of reperfusion improves mitochondrial
      dysfunction and cardiac contractility postmyocardial infarction in rats. METHODS
      AND RESULTS: We used a selective inhibitor of the fission machinery, P110, which
      we have recently designed. P110 treatment inhibited the interaction of fission
      proteins Fis1/Drp1, decreased mitochondrial fission, and improved bioenergetics
      in three different rat models of IR, including primary cardiomyocytes, ex vivo
      heart model, and an in vivo myocardial infarction model. Drp1 transiently bound
      to the mitochondria following IR injury and P110 treatment blocked this Drp1
      mitochondrial association. Compared with control treatment, P110 (1 MUmol/L)
      decreased infarct size by 28 +/- 2% and increased adenosine triphosphate levels
      by 70+1% after IR relative to control IR in the ex vivo model. Intraperitoneal
      injection of P110 (0.5 mg/kg) at the onset of reperfusion in an in vivo model
      resulted in improved mitochondrial oxygen consumption by 68% when measured 3
      weeks after ischemic injury, improved cardiac fractional shortening by 35%,
      reduced mitochondrial H2O2 uncoupling state by 70%, and improved overall
      mitochondrial functions. CONCLUSIONS: Together, we show that excessive
      mitochondrial fission at reperfusion contributes to long-term cardiac dysfunction
      in rats and that acute inhibition of excessive mitochondrial fission at the onset
      of reperfusion is sufficient to result in long-term benefits as evidenced by
      inhibiting cardiac dysfunction 3 weeks after acute myocardial infarction.

PMID- 24103572
TI  - Tracking Neospora caninum parasites using chimera monoclonal antibodies against
      its surface antigen-related sequences (rNcSRS2).
AB  - Neosporosis, an infectious disease of cattle and dogs, causes an abortion in
      cattle, which has a major damage on the dairy industry worldwide. Tracking of
      Neospora caninum parasite that is responsible for neosporosis is required for the
      prevention of this infectious disease. We developed three chimera monoclonal
      antibodies consist of variable regions of murine antibody and constant regions of
      human antibody against N. caninum. Recombinant surface antigen-related sequence 2
      (rNcSRS2) of N. caninum was expressed in silkworm larvae, and immunized in mice
      to obtain phage displaying antibody library. Through three rounds of selection,
      three antibodies, A6, E1 and H3, were isolated and bound to rNcSRS2 with
      nanomolar to micromolar affinity. In immunofluorescent staining assays, A6 and E1
      bound to N. caninum strain Nc-Liv, demonstrating a successful tracking of the
      parasite. H3 clone bound to rNcSRS2 but not to a truncated protein without
      glycosylphosphatidylinositol (GPI) anchor domain in the carboxyl terminal. Amino
      acid sequences of A6 and E1 were similar, but that of H3 differed in the CDR-H1
      region, which might be the reason of their difference of affinity. These
      antibodies are thought to be useful for prevention of cattle from neosporosis.

PMID- 24103573
TI  - A population-based cohort study to elucidate temporal relationship between
      schizophrenia and metabolic syndrome (KCIS no. PSY3).
AB  - BACKGROUND: The bidirectional relationships between metabolic syndrome (MetS) and
      schizophrenia (SCZ) play a crucial role in clinical treatment of both diseases
      but such bidirectional causal effects have not been comprehensively elucidated.
      AIMS: To investigate the influence of MetS on incident SCZ and the opposite
      direction as well as their predictors for each direction with a population-based
      cohort sample. METHOD: We enrolled 76,545 subjects who had participated in a
      community-based health screening program during 1999-2004. After excluding those
      with the existing MetS or SCZ at baseline, the two normal prospective cohorts
      corresponding to each independent variable of MetS or SCZ, respectively, were
      followed over time to ascertain incident outcome of SCZ and MetS. The crude and
      adjusted hazard ratios for the effect of the predictor on each incident outcome
      were estimated after controlling for the possible confounding factors. RESULTS:
      The overall incidence rate (per 10(5)person-years) of SCZ was 61.15. The
      incidence rate in patients with MetS was lower than those without (44.24 versus
      64.20), indicating the presence of MetS failed to find an increased risk of
      developing incident SCZ. However, participants with abnormal waist circumference
      (WC) were two times (95% CI: 1.37 to 2.93) more likely to yield incident SCZ
      compared to those with normal WC. In the opposite direction, the incidence of
      MetS was statistically higher in patients with SCZ than those without SCZ (11.25%
      vs 7.94%, respectively), suggesting SCZ conferred a higher risk for yielding
      incident MetS (adjusted hazard ratio=1.89, 95% CI: 1.36, 2.63). CONCLUSIONS:
      After examining the bidirectional causal relationships between SCZ and MetS with
      the theoretically sound and large population-based prospective cohort study,
      central obesity, one of the individual components of MetS, was corroborated as an
      independent predictor for incident SCZ. Patients diagnosed with SCZ were at
      greater risk of having incident cases of MetS. Such significant temporal
      bidirectional relationships between SCZ and central obesity suggest a reciprocal
      interaction exits between SCZ and central obesity.

PMID- 24103574
TI  - Label-free electrochemical biosensor using home-made 10-methyl-3-nitro-acridone
      as indicator for picomolar detection of nuclear factor kappa B.
AB  - A new acridone derivative 10-methyl-3-nitro-acridone (MNA) with excellent
      electrochemical activity was synthesized in this paper. Using it as an
      electrochemical indicator, a signal-on and label-free electrochemical biosensor
      was developed for picomolar determination of nuclear factor kappa B (NF-kappaB)
      in serum. Initially, linear double-stranded DNA (dsDNA) probes, which contain a
      protein-binding site specific to NF-kappaB, were self-assembled on the surface of
      a glass carbon electrode (GCE). If the NF-kappaB was absent, the dsDNA probes
      were cut into ss-DNA fragments by the digestion of ExoIII, resulting in a low
      electrochemical signal of MNA due to the weak binding affinity of MNA to ss-DNA.
      On the contrary, in the presence of NF-kappaB, it could bind with the dsDNA
      probes at the specific site and hinder the digestion of ExoIII, resulting in a
      significant increase of electrochemical response due to the intercalation of MNA
      into the dsDNA probes. By employing the above strategy, this sensor could detect
      as low as 40 pM NF-kappaB with high specificity. To the best of our knowledge,
      the proposed sensor is the first attempt to use acridone derivative as an
      electrochemical indicator for NF-kappaB detection, which may represent a
      promising path toward clinical diagnosis and drug developments.

PMID- 24103575
TI  - Cell-based high-throughput odorant screening system through visualization on a
      microwell array.
AB  - The development of a cell-based high-throughput screening system has attracted
      much attention from researchers who study drug screening mechanisms and
      characterization of G-protein coupled receptors (GPCRs). Although olfactory
      receptors (ORs) constitute the largest group of GPCRs that play a critical role
      recognizing and discriminating odorants, only a few ORs have been characterized,
      and most remain orphan. The conventional cell-based assay system for
      characterizing GPCRs, including ORs, is very laborious, time consuming, and
      requires an expensive assay system. In this study, we developed a simple, low
      cost miniaturized odorant screening method by combining Micro-Electro-Mechanical
      system (MEMs) technique and visualization technique for detecting an odorant
      response. We fabricated PEG microwell from a photocrosslinkable polyethylene
      glycol diacrylate (PEGDA) solution and applied it to cell culture and a reverse
      transfection platform for cell-based high-throughput screening. For the first
      time, the olfactory receptors were expressed on the microwell platform using
      reverse transfection technique. The various olfactory receptors can be expressed
      simultaneously using this technique and the microwell spotted with olfactory
      receptor genes can be used as a high-throughput screening platform. The odorant
      response was detected via fluorescence analysis on the microwell using a cAMP
      response element (CRE) reporter assay. We tested this platform using four de
      orphaned ORs. This new cell-based screening method not only reduced numerous time
      consuming steps but also allowed for simple, efficient, and quantitative
      screening and patterning of large numbers of GPCRs including ORs, which can help
      to visualize the OR response to odorants on a microwell.

PMID- 24103577
TI  - Manipulation of anabolic and catabolic responses with bone morphogenetic protein
      and zoledronic acid in a rat spinal fusion model.
AB  - Bone fusion involves a complex set of regulated signaling pathways that control
      the formation of new bone matrix and the resorption of damaged bone matrix at the
      surgical site. It has been reported that systemically administering a single dose
      of zoledronic acid (ZA) at the optimal time increases the strength of the bone
      morphogenetic protein (BMP)-mediated callus. In the present study, we aimed to
      investigate the effect of BMP-2 and ZA in a rat spinal model. Sixty-seven rats
      were divided into 6 groups: group I (n=11) animals were implanted with a carrier
      alone, group II (n=12) animals were implanted with a carrier and a subcutaneous
      injection of ZA was administered 2weeks after surgery, group III (n=12) animals
      were implanted with a carrier containing 1MUg of rhBMP-2, group IV (n=12) animals
      were implanted with a carrier containing 1MUg of rhBMP-2 and a subcutaneous
      injection of ZA was administered 2weeks after surgery, group V (n=10) animals
      were implanted with a carrier containing 3MUg of rhBMP-2, and group VI (n=10)
      animals were implanted with a carrier containing 3MUg of rhBMP-2 and a
      subcutaneous injection of ZA was administered 2weeks after surgery. The rats were
      euthanized after 6weeks, and their spines were explanted and assessed by manual
      palpation, radiography, high-resolution micro-computerized tomography (micro-CT),
      and histologic analysis. The fusion rates in group VI (60%) were considerably
      higher than those in the groups I (0%), II (0%), III (12.5%), IV (20.8%), and V
      (35%), (P<0.05). Additionally, the radiographic scores of group VI were higher
      than those in the other groups, (P<0.05). In micro-CT analysis, the tissue and
      bone volumes of the callus were significantly higher in group VI than those in
      the other groups, (P<0.05). The trabecular number was significantly higher and
      the trabecular spacing was significantly lower in group VI than those in the
      other groups, (P<0.05). The combination of rhBMP-2 and ZA administered
      systemically as a single dose at the optimal time was efficacious in our rat
      spinal fusion model. Our results suggest that this combination facilitates spinal
      fusion and has potential clinical application. 

PMID- 24103576
TI  - ClC-7 expression levels critically regulate bone turnover, but not gastric acid
      secretion.
AB  - Mutations in the 2Cl(-)/1H(+)-exchanger ClC-7 impair osteoclast function and
      cause different types of osteoclast-rich osteopetrosis. However, it is unknown to
      what extent ClC-7 function has to be reduced to become rate-limiting for bone
      resorption. In osteoclasts from osteopetrosis patients expression of the mutated
      ClC-7 protein did not correlate with disease severity and resorption impairment.
      Therefore, a series of transgenic mice expressing ClC-7 in osteoclasts at
      different levels was generated. Crossing of these mice with Clcn7(-/-) mutants
      rescued the osteopetrotic phenotype to variable degrees. One resulting double
      transgenic line mimicked human autosomal dominant osteopetrosis. The trabecular
      bone of these mice showed a reduction of osteoblast numbers, osteoid, and
      osteoblast marker gene expression indicative of reduced osteoblast function. In
      osteoclasts from these mutants ClC-7 expression levels were 20 to 30% of wildtype
      levels. These reduced levels not only impaired resorptive activity, but also
      increased numbers, size and nucleus numbers of osteoclasts differentiated in
      vitro. Although ClC-7 was expressed in the stomach and PTH levels were high in
      Clcn7(-/-) mutants loss of ClC-7 did not entail a relevant elevation of gastric
      pH. In conclusion, we show that in our model a reduction of ClC-7 function by
      approximately 70% is sufficient to increase bone mass, but does not necessarily
      enhance bone formation. ClC-7 does not appear to be crucially involved in gastric
      acid secretion, which explains the absence of an osteopetrorickets phenotype in
      CLCN7-related osteopetrosis. 

PMID- 24103578
TI  - Multi-scale correlative microscopy investigation of both structure and chemistry
      of deformation twin bundles in Fe-Mn-C steel.
AB  - A multi-scale investigation of twin bundles in Fe-22Mn-0.6C (wt%) twinning
      induced plasticity steel after tensile deformation has been carried out by truly
      correlative means; using electron channelling contrast imaging combined with
      electron backscatter diffraction, high-resolution secondary ion mass
      spectrometry, scanning transmission electron microscopy, and atom probe
      tomography on the exact same region of interest in the sample. It was revealed
      that there was no significant segregation of Mn or C to the twin boundary
      interfaces. 

PMID- 24103579
TI  - Administration of antibiotics to ewes at the beginning of the dry-period.
AB  - The objective of the present paper is to review the significance of
      administration of antibiotics at the end of a lactation period/beginning of the
      dry-period in ewes. During the stage of active involution, there is an increased
      risk of new mastitis cases and recrudescence of subclinical infections that had
      occurred during the previous lactation period. The main pathogens involved in the
      so-called 'dry-period mastitis' are coagulase-negative staphylococci. The
      principle of antibiotic administration at the end of a lactation period involves
      the intramammary infusion of a preparation to both mammary glands of ewes in the
      flock. Although a variety of products is licensed for administration in ewes,
      preferably the product for administration should be selected on the results of
      susceptibility testing of bacteria to be isolated from samples from ewes in the
      flock. In many clinical studies from around the world, performed in dairy- or
      mutton-production flocks, administration of antimicrobial agents at the end of a
      lactation period has been found beneficial in curing intramammary infections
      present at cessation of a lactation period, as well as in minimising the risk for
      intramammary infections during the dry-period. In dairy flocks, there are also
      benefits from increase in milk yield and decrease flock bulk milk mean somatic
      cell counts during the subsequent lactation period. Antibiotic administration at
      drying-off may be performed to all animals in a flock ('complete') or only to
      those considered to be infected ('selective'). In all cases, after administration
      of the antibiotic, definite and complete cessation of the lactation period is
      essential for success of the procedure. Moreover, maintenance of the prescribed
      withdrawal periods is essential to safeguard public health. The procedure should
      always be applied as part of a strategic udder health management plan in a flock;
      implementation improves the welfare of animals and affords significant financial
      benefits to the farmer. A mastitis prevention scheme during lactation will
      minimise the incidence of the disease; effective treatment of cases of the
      disease during lactation will decrease the bacterial populations in the flock and
      limit risk of infection of other animals. Administration of antibiotics at the
      end of a lactation period will complement the above procedures and will
      contribute to improved mammary health for the forthcoming lactation period. 

PMID- 24103580
TI  - Novel 6beta-acylaminomorphinans with analgesic activity.
AB  - Aminomorphinans are a relatively young class of opioid drugs among which
      substances of high in vitro efficacy and favorable in vivo action are found. We
      report the synthesis and pharmacological evaluation of novel 6beta
      acylaminomorphinans. 6beta-Morphinamine and 6beta-codeinamine were
      stereoselectively synthesized by Mitsunobu reaction. The aminomorphinans were
      subsequently acylated with diversely substituted cinnamic acids. In vitro binding
      studies on cinnamoyl morphinamines showed moderate affinity for all opiate
      receptors with some selectivity for mu opioid receptors, while cinnamoyl
      codeinamines only showed affinity for mu opioid receptors. In vivo analgesia
      studies showed significant analgesic activity of 6beta-cinnamoylmorphinamine
      mediated by mu and delta receptors. The lead compound was found to be roughly
      equipotent to morphine (ED50 3.13 +/- 1.09 mg/kg) but devoid of the dangerous
      side-effect respiratory depression, a major issue associated with traditional
      opioid therapy.

PMID- 24103581
TI  - Enhancement effect of dihydroartemisinin on human gammadelta T cell proliferation
      and killing pancreatic cancer cells.
AB  - gammadelta T cells play important roles in innate immunity against tumors and
      infections. Inhibitory effect of dihydroartemisinin on growth of cancer cells has
      been found in recent years. In this study, we investigated the effect of
      dihydroartemisinin on human gammadelta T cell proliferation by MTT assay and
      killing activity against pancreatic cancer cells SW1990, BxPC-3 and PANC-1 by LDH
      release assay in vitro. Intracellular molecule alterations were verified by flow
      cytometry. The results suggested that appropriate concentration of
      dihydroartemisinin favored the expansion of gammadelta T cells and enhanced
      gammadelta T cell mediated killing activity against pancreatic cancer cells. Up
      regulation of intracellular perforin, granzyme B expression and IFN-gamma
      production may be the important mechanism of dihydroartemisinin on increased
      antitumor activity of gammadelta T cells. 

PMID- 24103582
TI  - A 5 item version of the Compliance Questionnaire for Rheumatology (CQR5)
      successfully identifies low adherence to DMARDs.
AB  - BACKGROUND: Taking DMARDs as prescribed is an essential part of self-management
      for patients with Rheumatoid Arthritis. To date, the Compliance Questionnaire for
      Rheumatology (CQR) is the only self-report adherence measure created specifically
      for and validated in rheumatic diseases. However, the factor structure of the CQR
      has not been reported and it can be considered lengthy at 19 items. The aim of
      this study was to test the factor structure of the CQR and reduce the number of
      items whilst retaining robust explanation of non-adherence to DMARDs. Such a
      reduction would increase the clinical utility of the scale, to identify patients
      with sub-optimal adherence to DMARDs in the clinic as well as for research
      purposes. METHODS: An exploratory factor analysis was performed to reduce the
      number of items in the CQR and then a confirmatory factor analysis was run to
      establish the fit of a 5 item version (CQR5) to the data. A discriminant function
      analysis was performed to determine the optimal combination of questions to
      identify suboptimal adherence. RESULTS: The factor analyses identified a
      unidimensional 5 item model that explains 50.3% of the variance in adherence and
      has good internal consistency and fit to the data. Discriminant function analysis
      shows that the CQR5 can affectively detect 69% of low adherers to DMARDs using
      Fisher's weighted regression equation. CONCLUSION: A shortened version of the CQR
      increases the clinical utility by reducing the patient burden whilst maintaining
      a good level of reliability and validity for a short, self-administered, self
      report questionnaire.

PMID- 24103583
TI  - MSX1 and PAX9 investigation in monozygotic twins with variable expression of
      tooth agenesis.
AB  - Non-syndromic agenesis of permanent teeth is one of the most common anomalies in
      human development, a multifactorial characteristic caused by genetic and
      environmental factors. We describe a pair of monozygotic twins who showed second
      premolar and third molar agenesis, albeit with different expressions. We studied
      the DNA of two genes, paired domain box gene 9 (PAX9) and muscle segment
      homeodomain-homeobox1 (MSX1), encoding transcription factors that earlier studies
      found were involved in the manifestation of this condition. No specific causative
      mutation was found. However, we detected a C->T change in MSX1 exon 2 in both
      twins, suggesting that this polymorphism might be involved in the trait's
      expression. 

PMID- 24103584
TI  - Another step in improving the diagnosis of disseminated intravascular coagulation
      in sepsis.
AB  - The diagnosis of disseminated intravascular coagulation (DIC) based on composite
      scoring systems using routinely available coagulation tests has been greatly
      facilitated. Such scoring instruments not only adequately assess the presence of
      DIC but also have strong prognostic power for morbidity and mortality. In this
      issue of Critical Care, Gando and colleagues report on the prospective validation
      of the Japanese Association of Acute Medicine score for DIC in patients with
      severe sepsis. 

PMID- 24103585
TI  - Atypical brain lateralisation in the auditory cortex and language performance in
      3- to 7-year-old children with high-functioning autism spectrum disorder: a child
      customised magnetoencephalography (MEG) study.
AB  - BACKGROUND: Magnetoencephalography (MEG) is used to measure the auditory evoked
      magnetic field (AEF), which reflects language-related performance. In young
      children, however, the simultaneous quantification of the bilateral auditory
      evoked response during binaural hearing is difficult using conventional adult
      sized MEG systems. Recently, a child-customised MEG device has facilitated the
      acquisition of bi-hemispheric recordings, even in young children. Using the child
      customised MEG device, we previously reported that language-related performance
      was reflected in the strength of the early component (P50m) of the auditory
      evoked magnetic field (AEF) in typically developing (TD) young children (2 to 5
      years old) [Eur J Neurosci 2012, 35:644-650]. The aim of this study was to
      investigate how this neurophysiological index in each hemisphere is correlated
      with language performance in autism spectrum disorder (ASD) and TD children.
      METHODS: We used magnetoencephalography (MEG) to measure the auditory evoked
      magnetic field (AEF), which reflects language-related performance. We
      investigated the P50m that is evoked by voice stimuli (/ne/) bilaterally in 33
      young children (3 to 7 years old) with ASD and in 30 young children who were
      typically developing (TD). The children were matched according to their age (in
      months) and gender. Most of the children with ASD were high-functioning subjects.
      RESULTS: The results showed that the children with ASD exhibited significantly
      less leftward lateralisation in their P50m intensity compared with the TD
      children. Furthermore, the results of a multiple regression analysis indicated
      that a shorter P50m latency in both hemispheres was specifically correlated with
      higher language-related performance in the TD children, whereas this latency was
      not correlated with non-verbal cognitive performance or chronological age. The
      children with ASD did not show any correlation between P50m latency and language
      related performance; instead, increasing chronological age was a significant
      predictor of shorter P50m latency in the right hemisphere. CONCLUSIONS: Using a
      child-customised MEG device, we studied the P50m component that was evoked
      through binaural human voice stimuli in young ASD and TD children to examine
      differences in auditory cortex function that are associated with language
      development. Our results suggest that there is atypical brain function in the
      auditory cortex in young children with ASD, regardless of language development.

PMID- 24103586
TI  - A semiparametric approach to estimate rapid lung function decline in cystic
      fibrosis.
AB  - PURPOSE: Detecting the onset of rapid lung function decline is important to
      reduce mortality rates in cystic fibrosis (CF) and other lung diseases. The most
      common approach is conventional linear mixed modeling-estimating a population
      level slope of lung function decline and using random effects to address serial
      correlation-but this ignores nonlinear features of disease progression and
      distinct sources of variability. The purpose of this article was to estimate
      patient-specific timing and degree of rapid decline while appropriately
      characterizing natural progression and variation in CF. METHODS: We propose
      longitudinal semiparametric mixed modeling and contrast it with the conventional
      approach, which restricts lung function (measured as forced expiratory volume in
      1 second as a percentage of predicted, FEV1%) to linear decline. Each approach is
      applied to clinical encounter data from the United States CF Foundation Patient
      Registry. RESULTS: Timing and degree of rapid FEV1% decline vary across patients
      and as a function of key covariates. Patients experience maximal FEV1% loss by
      early adulthood more severe than indicated by conventional slope analysis.
      CONCLUSIONS: Semiparametric mixed modeling provides a means to estimate patient
      specific changes in CF disease progression and may be used to inform prognostic
      decisions in chronic care settings and clinical studies.

PMID- 24103587
TI  - Replacement of acetate with citrate in dialysis fluid: a randomized clinical
      trial of short term safety and fluid biocompatibility.
AB  - BACKGROUND: The majority of bicarbonate based dialysis fluids are acidified with
      acetate. Citrate, a well known anticoagulant and antioxidant, has been suggested
      as a biocompatible alternative. The objective of this study was to evaluate short
      term safety and biocompatibility of a citrate containing acetate-free dialysis
      fluid. METHODS: Twenty four (24) patients on maintenance dialysis three times per
      week, 13 on on-line hemodiafiltration (HDF) and 11 on hemodialysis (HD), were
      randomly assigned to start with either citrate dialysis fluid (1 mM citrate, 1.5
      mM calcium) or control fluid (3 mM acetate, 1.5 mM calcium) in an open-labeled
      cross-over trial (6 + 6 weeks with 8 treatments wash-out in between). Twenty (20)
      patients, 11 on HDF and 9 on HD were included in the analyses. Main objective was
      short term safety assessed by acid-base status, plasma ionized calcium and
      parathyroid hormone (PTH). In addition, biocompatibility was assessed by markers
      of inflammation (pentraxin 3 (PTX-3), CRP, IL-6, TNF-alpha and IL-1beta) and
      thrombogenicity (activated partial thromboplastin time (APTT) and visual clotting
      scores). RESULTS: No differences dependent on randomization order or treatment
      mode (HD vs. HDF) were detected. Citrate in the dialysis fluid reduced the intra
      dialytic shift in pH (+0.04 week 6 vs. +0.06 week 0, p = 0.046) and base excess
      (+3.9 mM week 6 vs. +5.6 mM week 0, p = 0.006) over the study period. Using the
      same calcium concentration (1.5 mM), citrate dialysis fluid resulted in lower
      post-dialysis plasma ionized calcium level (1.10 mM vs. 1.27 mM for control, p <
      0.0001) and higher post-dialysis PTH level (28.8 pM vs. 14.7 pM for control, p <
      0.0001) while pre-dialysis levels were unaffected. Citrate reduced intra-dialytic
      induction of PTX-3 (+1.1 ng/ml vs. +1.4 ng/ml for control, p = 0.04) but had no
      effect on other markers of inflammation or oxidative stress. Citrate reduced
      visual clotting in the arterial air chamber during HDF (1.0 vs. 1.8 for control,
      p = 0.03) and caused an intra-dialytic increase in APTT (+6.8 s, p = 0.003)
      without affecting post-dialysis values compared to control. CONCLUSIONS: During
      this small short term study citrate dialysis fluid was apparently safe to use in
      HD and on-line HDF treatments. Indications of reduced treatment-induced
      inflammation and thrombogenicity suggest citrate as a biocompatible alternative
      to acetate in dialysis fluid. However, the results need to be confirmed in long
      term studies. TRIAL REGISTRATION ISRCTN: ISRCTN28536511.

PMID- 24103589
TI  - The complex understanding of Annexin A1 phosphorylation.
AB  - Annexin A1 (ANXA1) is the first characterized member of the annexins superfamily.
      It binds the cellular membrane phospholipids in Ca(2+) regulated manner. Annexin
      A1 has been found in several tissues and many physiological roles as hormones
      secretion, vesiculation, inflammatory response, apoptosis and differentiation
      have been shown. Its subcellular localization and binding with many partner
      proteins are altered accordingly with its physiological role. The Annexin A1
      membrane localization is crucial for binding to receptors, suggesting a paracrine
      and juxtacrine extracellular action. Annexin A1 is subjected to several post
      translational modifications. In particular the protein is phosphorylated on
      several residues both on the N-terminal functional domain and on the C-terminus
      core. Different kinases have been identified as responsible for the
      phosphorylation status of selective residues. The specific change in the
      phosphorylation status on the different sites alters ANXA1 localization, binding
      properties and functions. This review shows the physiological relevance of the
      ANXA1 phosphorylation leading to the conclusion that numerous and different roles
      of Annexin A1 could be associated with different phosphorylations to alter not
      only intracellular localization and bindings to its partners but also the
      extracellular receptor interactions. 

PMID- 24103588
TI  - Molecular bases of chronic lymphocytic leukemia in light of new treatments.
AB  - The human genome era heralded a fundamental progress in the field of cancer
      genetics that shifted from a candidate gene approach toward global views of
      genomes and transcriptomes. Whole genome/exome sequencing has disclosed the
      genetic landscape of several hematologic tumors, providing comprehensive catalogs
      of somatic mutations and new insights into the genes that contribute to cellular
      transformation. Thanks to these technical progresses, research on the molecular
      pathogenesis of chronic lymphocytic leukemia (CLL) has also advanced at a
      sustained pace in recent times revealing NOTCH1, SF3B1, BIRC3, and MYD88 as the
      most recurrently (>5%) mutated genes that have been identified in CLL. Beside
      mutations of cancer related genes, another mechanism involved in disease
      initiation and progression of mature B-cell tumors, including CLL, is represented
      by B cell receptor (BCR) signaling. The BCR plays a central role in disease
      pathogenesis and, consequently, BCR signaling might represent a suitable target
      for therapy in many patients. Currently, the Bruton tyrosine kinase (BTK)
      inhibitor ibrutinib, which acts downstream the BCR signaling pathway, appears to
      be particularly promising and shows important clinical activity in CLL. 

PMID- 24103590
TI  - RanBPM interacts with TbetaRI, TRAF6 and curbs TGF induced nuclear accumulation
      of TbetaRI.
AB  - Transforming growth factor beta (TGF-beta), a cytokine, and its receptors play a
      vital role during normal embryogenesis, cell proliferation, differentiation,
      apoptosis and migration. Ran-binding protein in the microtubule-organizing center
      (RanBPM) serves as a scaffold protein that has been shown to interact with many
      other proteins, such as MET, Axl/Sky, TRAF6, IFNR, TrKA and TrkB in addition to
      p75NTR. In the current study, we have identified RanBPM as a novel binding
      partner of TbetaRI by yeast two-hybrid assay. The TbetaRI and RanBPM association
      was confirmed by co-immunoprecipitation and GST pull-down experiments.
      Additionally, expression of RanBPM abrogated the interaction between TbetaRI and
      TRAF6. Furthermore, RanBPM could depress TGF-beta induced TRAF6 ubiquitination,
      subsequent NF-kappaB signaling pathway, and block TGF-beta induced TbetaRI
      nuclear accumulation. Taken together, our results reveal that RanBPM may modulate
      TGF-beta-mediated downstream signaling and biological functions. 

PMID- 24103591
TI  - Cost-effectiveness analysis of treatment with peginterferon-alfa-2a versus
      peginterferon-alfa-2b for patients with chronic hepatitis C under the public
      payer perspective in Brazil.
AB  - BACKGROUND: Chronic hepatitis C affects approximately 170 million people
      worldwide, and thus being one of the main causes of chronic liver disease. About
      20% of patients with chronic hepatitis C will develop cirrhosis over 20 years,
      and present an increased risk of developing hepatic complications. Sustained
      virological response (SVR) is associated with a better prognosis compared to
      untreated patients and treatment failures.The objective of this analysis was to
      compare treatment costs and outcomes of pegylated interferon-alfa-2a versus
      pegylated interferon-alfa-2b, both associated with ribavirin, in the therapeutic
      scheme of 24 weeks and 48 week for hepatitis C genotypes 2/3 and genotype 1,
      respectively, under the Brazilian Public Health System (SUS) scenario. METHODS:
      To project disease progression, a Markov model was built based on clinical stages
      of chronic disease. A Delphi panel was conducted to evaluate medical resources
      related to each stage, followed by costing of related materials, services,
      procedures and pharmaceutical products. The evaluation was made from a public
      payer perspective. The source used for costing was government reimbursement
      procedures list (SAI/SIH-SUS). Drug acquisition costs were obtained from the
      Brazilian Official Gazette and "Banco de Precos em Saude" (government official
      source). It was assumed a mean patient weight of 70 kg. Costs were reported in
      2011 Brazilian Reais (US$1 ~ $Brz1.80). A systematic review followed by a meta
      analysis of the 7 identified randomized controlled trials (RCTs) which compared
      pegylated interferons, was conducted for obtaining relative efficacy of both
      drugs: for genotype 2/3, mean rate of SVR was 79.2% for peginterferon-alfa-2a and
      73.8% for peginterferon-alfa-2b. For genotype 1, SVR mean rate was 42.09% versus
      33.44% (peginterferon-alfa-2a and peginterferon-alfa-2b respectively). Time
      horizon considered was lifetime. Discount rate for costs and outcomes was 5%,
      according to Brazilian guidelines for Health Technology Assessment (HTA).
      RESULTS: Analysis showed that peginterferon-alfa-2a is a dominant therapy
      compared to peginterferon-alfa-2b for genotype 1 ($Brz 4,345 savings and 0.10
      LY/0.25 QALY gains) as well for genotype 2/3 ($Brz 8,001 savings and 0.16 LY/0.39
      QALY gains). Projections indicated that for each 1000 patients treated with
      peginterferon-alfa-2a instead of peginterferon-alfa-2b, the amount of resources
      saved would be of $Brz 4.3 million for genotypes 2/3 and up to $Brz 8 million for
      genotype 1. CONCLUSION: These findings suggest that treatment with peginterferon
      alfa-2a is more effective and less costly when compared to peginterferon-alfa-2b
      under SUS perspective in Brazil.

PMID- 24103592
TI  - Measuring family caregiver efficacy for managing behavioral and psychological
      symptoms in dementia: a psychometric evaluation.
AB  - BACKGROUND: Caregiver efficacy for managing the behavioral and psychological
      symptoms of dementia (BPSD) is an important determinant of family caregiver
      stress and burden. This study aims to develop a measure of caregiver efficacy for
      responding to BPSD and to evaluate its psychometric properties. METHODS: The
      Caregiver Efficacy Scale adds an item for caregiver confidence in managing BPSD
      to each domain of the Neuropsychiatric Inventory (NPI). The validity, internal
      consistency, and factor structure of the scale were evaluated in 245 family
      caregivers. RESULTS: The results provide adequate support for the validity and
      reliability of the Caregiver Efficacy Scale. The internal consistency was found
      to be adequate (Cronbach's alpha = 0.79) and the scale demonstrated good
      concurrent, construct, and criterion validity. As expected, performance on the
      Caregiver Efficacy Scale was associated with all dimensions of the NPI, including
      BPSD frequency (r = 0.869, p < 0.01) and severity (r = 0.883, p < 0.01), and
      negative outcomes, including negative affect (r = 0.411, p < 0.01), depression (r
      = 0.362, p < 0.01), anxiety (r = 0.376, p < 0.01), and distress (r = 0.865, p <
      0.01). CONCLUSIONS: The Caregiver Efficacy Scale might have clinical implications
      in facilitating the development of improved caregiver interventions for dealing
      with BPSD, allowing interventions to be tailored according to individual
      caregiver needs, and also in evaluating the effectiveness of interventions aimed
      at improving caregiver self-efficacy for managing BPSD.

PMID- 24103593
TI  - What about politics and culture?
AB  - Given Van de Vliert's impressive dataset and prognoses, I will discuss three
      limitations. First, the evolutionary argument does not adequately take into
      account how political changes influence freedoms. Second, the operationalizations
      of needs and freedoms are limited and questionable. Third, a direct relationship
      between climate, monetary resources, and psychological variables is a
      simplification neglecting various intervening variables. 

PMID- 24103594
TI  - Navigating in a three-dimensional world.
AB  - The study of spatial cognition has provided considerable insight into how animals
      (including humans) navigate on the horizontal plane. However, the real world is
      three-dimensional, having a complex topography including both horizontal and
      vertical features, which presents additional challenges for representation and
      navigation. The present article reviews the emerging behavioral and
      neurobiological literature on spatial cognition in non-horizontal environments.
      We suggest that three-dimensional spaces are represented in a quasi-planar
      fashion, with space in the plane of locomotion being computed separately and
      represented differently from space in the orthogonal axis - a representational
      structure we have termed "bicoded." We argue that the mammalian spatial
      representation in surface-travelling animals comprises a mosaic of these locally
      planar fragments, rather than a fully integrated volumetric map. More generally,
      this may be true even for species that can move freely in all three dimensions,
      such as birds and fish. We outline the evidence supporting this view, together
      with the adaptive advantages of such a scheme.

PMID- 24103595
TI  - Semantic sides of three-dimensional space representation.
AB  - In this commentary, I propose that horizontal and vertical dimensions of space
      are represented together inside a common metrics mechanism located in the
      parietal cortex. Importantly, this network is also involved in the processing of
      number magnitudes and environment-directed actions. Altogether, the evidence
      suggests that different magnitude dimensions could be intertwined with the
      horizontality and verticality of our world representation.

PMID- 24103596
TI  - Human path navigation in a three-dimensional world.
AB  - Jeffery et al. propose a non-uniform representation of three-dimensional space
      during navigation. Fittingly, we recently revealed asymmetries between horizontal
      and vertical path integration in humans. We agree that representing navigation in
      more than two dimensions increases computational load and suggest that tendencies
      to maintain upright head posture may help constrain computational processing,
      while distorting neural representation of three-dimensional navigation.

PMID- 24103597
TI  - Learning landmarks and routes in multi-floored buildings.
AB  - Existing studies have proposed that humans preferentially memorize buildings as a
      collection of floors. Yet this might stem from the fact that environments were
      also explored by floors. We have studied this potential bias with a learning and
      recognition experiment. We have detected a positive influence of the learning
      route - by floors, and also crucially by columns - on spatial memory
      performances.

PMID- 24103598
TI  - Anisotropy and polarization of space: evidence from naive optics and
      phenomenological psychophysics.
AB  - Additional evidence is presented concerning the anisotropy between vertical and
      horizontal encoding, which emerges from studies of human perception and cognition
      of space in plane mirror reflections. Moreover, it is suggested that the non
      metric characteristic of polarization - that Jeffery et al. discuss with respect
      to gravity - is not limited to the vertical dimension.

PMID- 24103599
TI  - Navigating in a volumetric world: metric encoding in the vertical axis of space.
AB  - Animals navigate through three-dimensional environments, but we argue that the
      way they encode three-dimensional spatial information is shaped by how they use
      the vertical component of space. We agree with Jeffery et al. that the
      representation of three-dimensional space in vertebrates is probably bicoded
      (with separation of the plane of locomotion and its orthogonal axis), but we
      believe that their suggestion that the vertical axis is stored "contextually"
      (that is, not containing distance or direction metrics usable for novel
      computations) is unlikely, and as yet unsupported. We describe potential
      experimental protocols that could clarify these differences in opinion
      empirically.

PMID- 24103600
TI  - Navigating through a volumetric world does not imply needing a full three
      dimensional representation.

PMID- 24103601
TI  - Think local, act global: how do fragmented representations of space allow
      seamless navigation?
AB  - In this commentary, we highlight a difficulty for metric navigation arising from
      recent data with grid and place cells: the integration of piecemeal
      representations of space in environments with repeated boundaries. Put simply, it
      is unclear how place and grid cells might provide a global representation of
      distance when their fields appear to represent repeated boundaries within an
      environment. One implication of this is that the capacity for spatial inferences
      may be limited.

PMID- 24103602
TI  - Perceptual experience as a bridge between the retina and a bicoded cognitive map.
AB  - The bicoded cognitive maps described by Jeffery et al. are compared to metric
      perceptual representations. Systematic biases in perceptual experience of
      egocentric distance, height, and surface orientation may reflect information
      processing choices to retain information critical for immediate action (Durgin et
      al. 2010a). Different information processing goals (route planning vs. immediate
      action) require different metric information.

PMID- 24103603
TI  - Learning to navigate in a three-dimensional world: from bees to primates.
AB  - We discuss the idea that environmental factors influence the neural mechanisms
      that evolved to enable navigation, and propose that a capacity to learn different
      spatial relationship rules through experience may contribute to bicoded
      processing. Recent experiments show that free-flying bees can learn abstract
      spatial relationships, and we propose that this could be combined with optic flow
      processing to enable three-dimensional navigation.

PMID- 24103604
TI  - Spatial language as a window on representations of three-dimensional space.
AB  - Recent research investigating the language-thought interface in the spatial
      domain points to representations of the horizontal and vertical dimensions that
      closely resemble those posited by Jeffery et al. However, the findings suggest
      that such representations, rather than being tied to navigation, may instead
      reflect more general properties of the perception of space.

PMID- 24103605
TI  - Multi-floor buildings and human wayfinding cognition.
AB  - Multilevel wayfinding research in environmental psychology and architecture
      exhibits a strong compatibility with Jeffery et al.'s "bicoded" representation of
      space. We identify a need for capturing verticality in spatial analysis
      techniques such as space syntax and argue for investigating inter-individual
      differences in the ability to mentally integrate the cognitive maps of separate
      floors in buildings.

PMID- 24103606
TI  - Applying the bicoded spatial model to nonhuman primates in an arboreal multilayer
      environment.
AB  - Applying the framework proposed by Jeffery et al. to nonhuman primates moving in
      multilayer arboreal and terrestrial environments, we see that these animals must
      generate a mosaic of many bicoded spaces in order to move efficiently and safely
      through their habitat. Terrestrial light detection and ranging (LiDAR) technology
      and three-dimensional modelling of canopy movement may permit testing of Jeffery
      et al.'s framework in natural environments.

PMID- 24103607
TI  - The complex interplay between three-dimensional egocentric and allocentric
      spatial representation.
AB  - Jeffery et al. characterize the egocentric/allocentric distinction as discrete.
      But paradoxically, much of the neural and behavioral evidence they adduce
      undermines a discrete distinction. More strikingly, their positive proposal - the
      bicoded map hypothesis - reflects a more complex interplay between egocentric and
      allocentric coding than they acknowledge. Properly interpreted, their proposal
      about three-dimensional spatial representation contributes to recent work on
      embodied cognition.

PMID- 24103608
TI  - The planar mosaic fails to account for spatially directed action.
AB  - Humans' spatial representations enable navigation and reaching to targets above
      the ground plane, even without direct perceptual support. Such abilities are
      inconsistent with an impoverished representation of the third dimension. Features
      that differentiate humans from most terrestrial animals, including raised eye
      height and arms dedicated to manipulation rather than locomotion, have led to
      robust metric representations of volumetric space.

PMID- 24103609
TI  - Monkeys in space: primate neural data suggest volumetric representations.
AB  - The target article does not consider neural data on primate spatial
      representations, which we suggest provide grounds for believing that navigational
      space may be three-dimensional rather than quasi-two-dimensional. Furthermore, we
      question the authors' interpretation of rat neurophysiological data as indicating
      that the vertical dimension may be encoded in a neural structure separate from
      the two horizontal dimensions.

PMID- 24103610
TI  - Development of human spatial cognition in a three-dimensional world.
AB  - Jeffery et al. accurately identify the importance of developing an understanding
      of spatial reference frames in a three-dimensional world. We examine human
      spatial cognition via a unique paradigm that investigates the role of saliency
      and adjusting reference frames. This includes work with adults, typically
      developing children, and children who develop non-typically (e.g., those with
      autism).

PMID- 24103611
TI  - Has a fully three-dimensional space map never evolved in any species? A
      comparative imperative for studies of spatial cognition.
AB  - I propose that it is premature to assert that a fully three-dimensional map has
      never evolved in any species, as data are lacking to show that space coding in
      all animals is the same. Instead, I hypothesize that three-dimensional
      representation is tied to an animal's mode of locomotion through space. Testing
      this hypothesis requires a large body of comparative data.

PMID- 24103612
TI  - Making a stronger case for comparative research to investigate the behavioral and
      neurological bases of three-dimensional navigation.
AB  - The rich diversity of avian natural history provides exciting possibilities for
      comparative research aimed at understanding three-dimensional navigation. We
      propose some hypotheses relating differences in natural history to potential
      behavioral and neurological adaptations possessed by contrasting bird species.
      This comparative approach may offer unique insights into some of the important
      questions raised by Jeffery et al.

PMID- 24103613
TI  - Which animal model for understanding human navigation in a three-dimensional
      world?
AB  - Single-cell studies of monkey posterior parietal cortex (PPC) have revealed the
      extensive neuronal representations of three-dimensional subject motion and three
      dimensional layout of the environment. I propose that navigational planning
      integrates this PPC information, including gravity signals, with horizontal-plane
      based information provided by the hippocampal formation, modified in primates by
      expansion of the ventral stream.

PMID- 24103614
TI  - The study of blindness and technology can reveal the mechanisms of three
      dimensional navigation.
AB  - Jeffery et al. suggest that three-dimensional environments are not represented
      according to their volumetric properties, but in a quasi-planar fashion. Here we
      take into consideration the role of visual experience and the use of technology
      for spatial learning to better understand the nature of the preference of
      horizontal over vertical spatial representation.

PMID- 24103615
TI  - Augmented topological maps for three-dimensional navigation.
AB  - We describe an augmented topological map as an alternative for the proposed
      bicoded map. Inverting causality, the special nature of the vertical dimension is
      then no longer fixed a priori and the cause of specific navigation behavior, but
      a consequence of the combination of the specific geometry of the experimental
      environment and the motor capabilities of the experimental animals.

PMID- 24103616
TI  - Navigation bicoded as functions of x-y and time?
AB  - Evidence from egocentric space is cited to support bicoding of navigation in
      three-dimensional space. Horizontal distances and space are processed differently
      from the vertical. Indeed, effector systems are compatible in horizontal space,
      but potentially incompatible (or chaotic) during transitions to vertical motion.
      Navigation involves changes in coordinates, and animal models of navigation
      indicate that time has an important role.

PMID- 24103617
TI  - Vertical and veridical--2.5-dimensional visual and vestibular navigation.
AB  - Does the psychological and neurological evidence concerning three-dimensional
      localization and navigation fly in the face of optimality? This commentary brings
      a computational and robotic engineering perspective to the question of
      "optimality" and argues that a multicoding manifold model is more efficient in
      several senses, and is also likely to extend to "volume-travelling" animals,
      including birds or fish.

PMID- 24103618
TI  - Foreshortening affects both uphill and downhill slope perception at far
      distances.
AB  - Perceived slope varies with the viewing distance, and is consistent with the
      effects of foreshortening. Distant viewing makes uphill slopes appear steeper and
      downhill slopes flatter than does near viewing. These effects are obvious to
      skiers and climbers in mountainous country. They have also been measured in
      outdoor experiments with controlled viewing distances. There are many other
      sources of slope illusions.

PMID- 24103619
TI  - The problem of conflicting reference frames when investigating three-dimensional
      space in surface-dwelling animals.
AB  - In a surface-dwelling animal like the rat, experimental strategies for
      investigating the hippocampal correlates of three-dimensional space appear
      inevitably complicated by the interplay of global versus local reference frames.
      We discuss the impact of the resulting confounds on present and future empirical
      analysis of the "bicoded map" hypothesis by Jeffery and colleagues.

PMID- 24103620
TI  - Just the tip of the iceberg: the bicoded map is but one instantiation of scalable
      spatial representation structures.
AB  - Although the bicoded map constitutes an interesting candidate representation,
      proposing it as the predominant representation for three-dimensional space is too
      restrictive. We present and argue for scalable spatial representation structures
      as a more comprehensive alternative account that includes the bicoded map as a
      special case.

PMID- 24103621
TI  - What is optimized in an optimal path?
AB  - An animal confronts numerous challenges when constructing an optimal navigational
      route. Spatial representations used for path optimization are likely constrained
      by critical environmental factors that dictate which neural systems control
      navigation. Multiple coding schemes depend upon their ecological relevance for a
      particular species, particularly when dealing with the third, or vertical,
      dimension of space.

PMID- 24103622
TI  - Grid maps for spaceflight, anyone? They are for free!
AB  - We show that, given extensive exploration of a three-dimensional volume, grid
      units can form with the approximate periodicity of a face-centered cubic crystal,
      as the spontaneous product of a self-organizing process at the single unit level,
      driven solely by firing rate adaptation.

PMID- 24103623
TI  - What counts as the evidence for three-dimensional and four-dimensional spatial
      representations?
AB  - The dimension of spatial representations can be assessed by above-chance
      performance in novel shortcut or spatial reasoning tasks independent of accuracy
      levels, systematic biases, mosaic/segmentation across space, separate coding of
      individual dimensions, and reference frames. Based on this criterion, humans and
      some other animals exhibited sufficient evidence for the existence of three
      dimensional and/or four-dimensional spatial representations.

PMID- 24103624
TI  - Are all types of vertical information created equal?
AB  - The vertical component of space occurs in two distinct fashions in natural
      environments. One kind of verticality is orthogonal-to-horizontal (as in climbing
      trees, operating in volumetric spaces such as water or air, or taking elevators
      in multilevel buildings). Another kind of verticality, which might be
      functionally distinct, comes from navigating on sloped terrain (as in traversing
      hills or ramps).

PMID- 24103625
TI  - Map fragmentation in two- and three-dimensional environments.
AB  - The suggestion that three-dimensional space is represented by a mosaic of neural
      map fragments, each covering a small area of space in the plane of locomotion,
      receives support from studies in complex two-dimensional environments. How map
      fragments are linked, which brain circuits are involved, and whether metric is
      preserved across fragments are questions that remain to be determined.

PMID- 24103626
TI  - Does evidence from ethology support bicoded cognitive maps?
AB  - The presumption that navigation requires a cognitive map leads to its conception
      as an abstract computational problem. Instead of loading the question in favor of
      an inquiry into the metric structure and evolutionary origin of cognitive maps,
      the task should first be to establish that a map-like representation actually is
      operative in real animals navigating real environments.

PMID- 24103627
TI  - Miller Fisher syndrome with positivity of anti-GAD antibodies.

PMID- 24103628
TI  - Endovascular versus microsurgical treatment of small intracranial aneurysms
      presenting with subarachnoid hemorrhage.

PMID- 24103629
TI  - Microsurgical versus endovascular treatment of ruptured intracranial aneurysms in
      young patients.

PMID- 24103630
TI  - Whole-body anatomy localization via classification and regression forests.

PMID- 24103631
TI  - Use of milk amyloid A in the diagnosis of subclinical mastitis in dairy ewes.
AB  - Subclinical mastitis (SM) is one of the most important diseases affecting dairy
      ewes worldwide, with negative impact on the animal health, farm income and public
      health. Animals with SM often remain untreated because the disease may not be
      revealed. Increase in somatic cell count (SCC) and positive bacteriology for
      mastitis pathogens in milk samples are indicative of SM but the evidence of only
      one of these alterations must suggest an uncertain SM (UM). UM is defined when
      positive bacteriological examination (Latent-SM) or SCC>500 000 cells/ml (non
      specific-SM) are detected in milk. Nevertheless, SCC and bacteriological
      examination are expensive, time consuming and are not yet in use at the farm
      level in dairy ewes. Recently, a sensitive acute phase protein, amyloid A,
      displaying multiple isoforms in plasma and different body fluids including
      mammary secretion (milk amyloid A-MAA), has been investigated as a marker of
      mastitis in cows and, in a few studies, in sheep. The aim of this trial was to
      compare the concentration of MAA of single udder-halves in ewes with healthy
      udder-halves (HU-control group) and naturally occurring subclinical mastitis,
      both confirmed (SM group) and uncertain (UM groups: Latent-SM and non-specific
      SM), for monitoring udder health. The reliability of a specific ELISA kit for the
      measurement of MAA was also tested. During a 3-month trial period, 153 udder
      halves were assigned to the experimental groups based on their health status: 25
      with SM, 40 with UM (11 with latent-SM and 29 with non-specific-SM) and 88 HU.
      SCC and bacteriological analysis were performed to establish the control and
      subclinical mastitis groups. MAA concentrations in milk samples were measured
      using a specific commercially milk ELISA kit. The data were submitted to
      statistical analysis. Significant (P<0.05) differences among the groups SM, non
      specific-SM and HU were detected with the SM having the highest level and HU the
      lowest. MAA concentration is affected by the udder health status and is a useful
      indicator of subclinical mastitis and increased SCC in sheep. 

PMID- 24103632
TI  - Genotype variant associated with add-on memantine in bipolar II disorder.
AB  - Memantine is a non-competitive N-methyl-d-asparate (NMDA) receptor antagonist
      with a mood-stabilizing effect. We investigated whether using valproic acid (VPA)
      plus add-on memantine to treat bipolar II disorder (BP-II) is more effective than
      using VPA alone (VPA + Pbo). We also evaluated, in BP-II patients, the
      association between the brain-derived neurotrophic factor (BDNF) Val66Met
      polymorphism with treatment response to VPA + add-on memantine and to VPA + Pbo.
      In this randomized, double-blind, controlled 12 wk study, BP-II patients
      undergoing regular VPA treatments were randomly assigned to a group: VPA +
      Memantine (5 mg/day) (n = 115) or VPA + Pbo (n = 117). The Hamilton Depression
      Rating Scale (HDRS) and Young Mania Rating Scale (YMRS) were used to evaluate
      clinical response during week 0, 1, 2, 4, 8 and 12. The genotypes of the BDNF
      Val66Met polymorphisms were determined using polymerase chain reactions plus
      restriction fragment length polymorphism analysis. To adjust within-subject
      dependence over repeated assessments, multiple linear regression with generalized
      estimating equation methods was used to analyze the effects of the BDNF Val66Met
      polymorphism on the clinical performance of memantine. Both groups showed
      significantly decreased YMRS and HDRS scores after 12 wk of treatment; the
      differences between groups were non-significant. When stratified by the BDNF
      Val66Met genotypes, significantly greater decreases in HDRS scores were found in
      the VPA + memantine group in patients with the Val Met genotype (p = 0.004). We
      conclude that the BDNF Val66Met polymorphism influenced responses to add-on
      memantine by decreasing depressive symptoms in patients with BP-II. 

PMID- 24103633
TI  - Effect of vancomycin dose on treatment outcomes in severe Clostridium difficile
      infection.
AB  - Current guidelines recommend vancomycin 125 mg four times daily for the treatment
      of severe Clostridium difficile infection (CDI). However, the optimal dose of
      vancomycin has not been elucidated. This study was conducted to evaluate outcome
      differences in patients with severe CDI treated with either low-dose (<=500 mg
      daily) or high-dose (>500 mg daily) oral vancomycin. The medical records of 78
      patients with severe CDI were evaluated retrospectively. The primary outcome was
      time to clinical cure of CDI, defined as the first day of resolution of diarrhoea
      for >=48 h without development of a complication. Other endpoints included cure
      rates, complication rates and recurrence rates. Overall, 48 patients (61.5%)
      achieved clinical cure at Day 10 after treatment initiation. The cure rates in
      the high-dose and low-dose vancomycin groups were 60% and 64%, respectively (P =
      0.76). Using a multivariate Cox proportional hazards model adjusting for baseline
      discrepancies, vancomycin dose was not independently associated with clinical
      cure. No difference in time to cure, complication rates or mortality was observed
      between the groups. There was a trend towards lower rates of recurrence
      associated with higher doses of oral vancomycin (12% vs. 1.9%; P = 0.09). In
      conclusion, these data suggest that there is no difference in treatment outcomes
      between high-dose and low-dose vancomycin for the treatment of severe CDI. The
      potential difference in recurrence rates between the groups warrants further
      investigation.

PMID- 24103634
TI  - Cardiorespiratory and antinociceptive effects of two different doses of lidocaine
      administered to horses during a constant intravenous infusion of xylazine and
      ketamine.
AB  - BACKGROUND: This study investigated the antinociceptive effects of a constant
      rate infusion (CRI) of lidocaine during xylazine and ketamine anesthesia in
      horses and aimed to correlate these effects with cardiorespiratory variables,
      bispectral index (BIS) and plasma lidocaine concentrations. Six adult crossbred
      mares weighing 320-400 kg were anesthetized on three different occasions.
      Sedation was performed with xylazine (0.75 mg/kg IV) and anesthetic induction
      with guaifenesin (75 mg/kg IV) and ketamine (2 mg/kg IV). Anesthesia was
      maintained with 37.5 MUg/kg/min of xylazine and 87.5 MUg/kg/min of ketamine both
      administered intravenously for 75 min. The three treatments consisted of:
      lidocaine (loading dose: 5 mg/kg, CRI: 100 MUg/kg/min; THL); lidocaine (loading
      dose: 2.5 mg/kg; CRI: 50 MUg/kg/min: TLL); and saline (TS); all given 15 min
      after induction and maintained for 1 h. Antinociception was measured by response
      to electrical stimulation and bispectral index (BIS) was recorded during
      anesthesia. Parametric and non-parametric data were compared using ANOVA followed
      by Student-Newman-Keuls and Friedman tests, respectively. RESULTS: Plasma
      lidocaine concentrations peaked at the end of lidocaine loading dose and was
      greater in THL (9.61 +/- 2.75 MUg/mL) vs TLL (4.50 +/- 3.34 MUg/mL). Electrical
      noxious stimulation caused purposeful movement in all horses from TS, but no
      response in THL. The BIS was decreased in THL only and was less when compared to
      the other treatments throughout anesthesia. Blood pressure, PaO2 and PaCO2
      increased and heart rate (HR), respiratory rate (RR), pH, total plasma protein
      and temperature decreased during anesthesia in all treatments. PaCO2 and HR were
      greater and RR and pH less in THL compared to TLL and TS at 30 min during
      anesthesia. All recoveries were considered excellent. Time to standing was longer
      after THL (60 +/- 20 min) than following TLL and TS (32 +/- 17 and 30 +/- 15 min,
      respectively). CONCLUSIONS: At the highest dose administered (THL) lidocaine CRI
      during xylazine/ketamine anesthesia decreased BIS and motor response to noxious
      stimulation, and prolonged recovery time without significant added
      cardiorespiratory depression.

PMID- 24103636
TI  - Enrichment analysis applied to disease prognosis.
AB  - : Enrichment analysis is well established in the field of transcriptomics, where
      it is used to identify relevant biological features that characterize a set of
      genes obtained in an experiment.This article proposes the application of
      enrichment analysis as a first step in a disease prognosis methodology, in
      particular of diseases with a strong genetic component. With this analysis the
      objective is to identify clinical and biological features that characterize
      groups of patients with a common disease, and that can be used to distinguish
      between groups of patients associated with disease-related events. Data mining
      methodologies can then be used to exploit those features, and assist medical
      doctors in the evaluation of the patients in respect to their predisposition for
      a specific event.In this work the disease hypertrophic cardiomyopathy (HCM) is
      used as a case-study, as a first test to assess the feasibility of the
      application of an enrichment analysis to disease prognosis. To perform this
      assessment, two groups of patients have been considered: patients that have
      suffered a sudden cardiac death episode and patients that have not.The results
      presented were obtained with genetic data and the Gene Ontology, in two
      enrichment analyses: an enrichment profiling aiming at characterizing a group of
      patients (e.g. that suffered a disease-related event) based on their mutations;
      and a differential enrichment aiming at identifying differentiating features
      between a sub-group of patients and all the patients with the disease. These
      analyses correspond to an adaptation of the standard enrichment analysis, since
      multiple sets of genes are being considered, one for each patient.The preliminary
      results are promising, as the sets of terms obtained reflect the current
      knowledge about the gene functions commonly altered in HCM patients, thus
      allowing their characterization. Nevertheless, some factors need to be taken into
      consideration before the full potential of the enrichment analysis in the
      prognosis methodology can be evaluated. One of such factors is the need to test
      the enrichment analysis with clinical data, in addition to genetic data, since
      both types of data are expected to be necessary for prognosis purposes. 

PMID- 24103635
TI  - Development and characterization of an orodispersible film containing drug
      nanoparticles.
AB  - In this study, a novel orodispersible film (ODF) containing drug nanoparticles
      was developed with the goal of transforming drug nanosuspensions into a solid
      dosage form and enhancing oral bioavailability of drugs with poor water
      solubility. Nanosuspensions were prepared by high pressure homogenization and
      then transformed into ODF containing drug nanoparticles by mixing with
      hydroxypropyl methylcellulose solution containing microcrystalline cellulose, low
      substituted hydroxypropylcellulose and PEG-400 followed by film casting and
      drying. Herpetrione, a novel and potent antiviral agent with poor water
      solubility that extracted from Herpetospermum caudigerum, was chosen as a model
      drug and studied systematically. The uniformity of dosage units of the
      preparation was acceptable according to the criteria of Japanese Pharmacopoeia
      15. The ODF was disintegrated in water within 30s with reconstituted
      nanosuspensions particle size of 280 +/- 11 nm, which was similar to that of drug
      nanosuspensions, indicating a good redispersibility of the fast dissolving film.
      Result of X-ray diffraction showed that HPE in the ODF was in the amorphous
      state. In the in vitro dissolution test, the ODF containing HPE nanoparticles
      showed an increased dissolution velocity markedly. In the pharmacokinetics study
      in rats, compared to HPE coarse suspensions, the ODF containing HPE nanoparticles
      exhibited significant increase in AUC0-24h, Cmax and decrease in Tmax, MRT. The
      result revealed that the ODF containing drug nanoparticles may provide a
      potential opportunity in transforming drug nanosuspensions into a solid dosage
      form as well as enhancing the dissolution rate and oral bioavailability of poorly
      water-soluble drugs.

PMID- 24103637
TI  - National reporting of in vitro fertilization success rates: how do we get
      patients useful information?

PMID- 24103638
TI  - Uterus transplantation research at the cutting edge?

PMID- 24103639
TI  - Contrast-enhanced ultrasound: a new vision of microcirculation in the intensive
      care unit.
AB  - To gain new insights into renal perfusion and pathogenesis of acute kidney injury
      in intensive care unit (ICU) patients, we need new techniques to evaluate renal
      microcirculation. In addition, a bedside technique applicable in the ICU could be
      extremely useful for physicians to adjust the optimal therapeutic/preventive
      modalities for kidney perfusion in each patient. Contrast-enhanced ultrasound
      (CEUS) has been validated to assess and quantify the microcirculation up to
      capillary perfusion in several organs. In a recent issue, Schneider and
      colleagues suggest that CEUS is feasible, well tolerated and able to quantify
      cortical renal microcirculation in patients undergoing cardiac surgery. In
      addition, CEUS derived-parameters suggest a decrease in renal perfusion occurring
      within 24 hours of surgery in patients at risk of acute kidney injury. This study
      opens up new possibilities for the assessment of cortical renal microcirculation
      in ICU patients.

PMID- 24103640
TI  - Cold shock Y-box protein-1 proteolysis autoregulates its transcriptional
      activities.
AB  - BACKGROUND: The Y-box protein-1 (YB-1) fulfills pleiotropic functions relating to
      gene transcription, mRNA processing, and translation. It remains elusive how YB-1
      shuttling into the nuclear and cytoplasmic compartments is regulated and whether
      limited proteolysis by the 20S proteasome releases fragments with distinct
      function(s) and subcellular distribution(s). RESULTS: To address these questions,
      mapping of domains responsible for subcellular targeting was performed. Three
      nuclear localization signals (NLS) were identified. NLS-1 (aa 149-156) and NLS-2
      (aa 185-194) correspond to residues with unknown function(s), whereas NLS-3 (aa
      276-292) matches with a designated multimerization domain. Nuclear export
      signal(s) were not identified. Endoproteolytic processing by the 20S proteasome
      before glycine 220 releases a carboxy-terminal fragment (CTF), which localized to
      the nucleus, indicating that NLS-3 is operative. Genotoxic stress induced
      proteolytic cleavage and nuclear translocation of the CTF. Co-expression of the
      CTF and full-length YB-1 resulted in an abrogated transcriptional activation of
      the MMP-2 promoter, indicating an autoregulatory inhibitory loop, whereas it
      fulfilled similar trans-repressive effects on the collagen type I promoter.
      CONCLUSION: Compartmentalization of YB-1 protein derivatives is controlled by
      distinct NLS, one of which targets a proteolytic cleavage product to the nucleus.
      We propose a model for an autoregulatory negative feedback loop that halts
      unlimited transcriptional activation.

PMID- 24103642
TI  - Inhibition of histone deacetylase in utero causes sociability deficits in
      postnatal mice.
AB  - Exposure to sodium valproate (VPA) in utero increases the risk of language
      impairment and a diagnosis of autism spectrum disorder (ASD). Mice exposed to VPA
      while in utero have also shown postnatal social deficits. Inhibition of histone
      deacetylase (HDAC) is one of VPA's many biological effects. The main objective of
      this study was to test the hypothesis that HDAC inhibition causes these
      behavioral outcomes following prenatal VPA exposure in mice. We exposed embryonic
      mice to VPA, the HDAC inhibitor trichostatin A (TSA), or vehicle controls. TSA
      (1mg/kg) inhibited HDAC in embryonic tissue at a level comparable to 600 mg/kg
      VPA, resulting in significant increases in histone H3 and H4 acetylation, and
      histone H3 lysine 4 tri-methylation. Postnatally, decreases in ultrasonic
      vocalization, olfactory motivation and sociability were observed in TSA and VPA
      exposed pups. Treated mice exhibited elevated digging and grooming suggestive of
      mild restrictive and repetitive behaviors. Olfactory social preference, social
      novelty and habituation were normal. Together, these data indicate that embryonic
      HDAC inhibition alone can cause abnormal social behaviors in mice. This result
      serves as a molecular understanding of infant outcomes following mild VPA
      exposure in utero.

PMID- 24103641
TI  - Time-dependence of risperidone and asenapine sensitization and associated D2
      receptor mechanism.
AB  - When an antipsychotic drug is given repeatedly and intermittently, there is often
      a long-term increase in its behavioral efficacy, termed antipsychotic
      sensitization. With the passage of time, the magnitude of antipsychotic
      sensitization may increase or decrease based on the principle of time-dependent
      sensitization (TDS) or memory decay, respectively. In the present study, we
      examined the time-dependent feature and possible dopamine D2 receptor mechanism
      of sensitization induced by risperidone and asenapine in the conditioned
      avoidance response test. Well-trained male adult Sprague-Dawley rats were first
      repeatedly treated with risperidone (1.0mg/kg) or asenapine (0.2mg/kg) and tested
      for avoidance response daily for 5 consecutive days. Eight, 18 or 38 days after
      the 5th drug treatment, all rats were retested drug-free to assess the long-term
      impact of prior risperidone or asenapine treatment. Drug-pretreated rats had
      significantly lower avoidance than vehicle-pretreated ones on this test, and the
      group differences increased with the passage of time. In the subsequent drug
      challenge test at 10, 20 or 40 days after the 5th drug treatment, all rats were
      injected with a low dose of risperidone (0.3mg/kg) or asenapine (0.1mg/kg). Drug
      pretreated rats again made significantly fewer avoidances than controls,
      confirming the antipsychotic sensitization effect. Finally, in the quinpirole (a
      D2/3 receptor agonist, 1.0mg/kg, sc)-induced hyperlocomotion test, risperidone
      pretreated rats exhibited a significantly higher level of motor activity than the
      vehicle-pretreated ones. These findings suggest that risperidone and asenapine
      sensitization is long-lasting, follows the TDS principle, and is likely mediated
      by D2 receptor supersensitivity. 

PMID- 24103643
TI  - A systematic review of metabolic side effects related to the use of antipsychotic
      drugs in dementia.
AB  - BACKGROUND: In clinical practice, Second Generation Antipsychotics (SGAs) are
      often used as first-line treatment for the Behavioral and Psychological Symptoms
      of Dementia (BPSD) in older adults due to their fewer neurological adverse events
      and similar effectiveness compared with First Generation Antipsychotics (FGAs).
      SGAs, however, are associated with more severe metabolic side effects (weight
      gain, hyperglycemia, diabetes risk, and hyperlipidemia) than FGAs are. In
      general, older patients, especially those affected by dementia, are at increased
      risk for malnutrition, and tend to have lower basal metabolism and reduced liver
      and kidney function. However, little is known about the metabolic side effects of
      antipsychotic drugs in this population. METHODS: A comprehensive review of the
      literature published between January 1996 and December 2012 investigating the
      metabolic side effects related to FGAs and SGAs use in old patients affected by
      dementia. RESULTS: Antipsychotic drugs currently used to treat BPSD in subjects
      with mild to moderate dementia are associated with weight gain. Currently, there
      are insufficient data to support a causal relationship between the use of FGAs
      and SGAs and changes in glucose homeostasis or lipid metabolism in older persons
      affected by severe dementia (MMSE <14). CONCLUSION: A possible association
      between antipsychotic drugs use and weight gain might exist, in particular in
      subjects with mild to moderate dementia whereas no significant effects are
      demonstrated regarding glucose homeostasis and lipid metabolism. The
      antipsychotic drugs potential for causing metabolic abnormalities in older
      patients requires further specifically designed studies. Clinicians must be aware
      of this possibility even if the shorter periods of treatment administered in late
      life might not be as harmful as it is in younger individuals.

PMID- 24103644
TI  - Use of an extruder for pre-mixing enhances xylanase action on wheat bran at low
      water content.
AB  - The aim of the work was to test the hypothesis that at low water content enzyme
      action on biomass is enhanced when the raw material is in the form of a
      continuous mass instead of powder/granular form. Effects of two pre-mixing
      methods, blade-mixing and extrusion, on xylanase action were studied during
      stationary incubation of wheat bran of different particle sizes, also in
      comparison with incubation at high water content with continuous stirring. The
      use of an extruder enhanced arabinoxylan (AX) solubilisation at low water content
      (<54%), as compared to blade-mixing. AX solubilisation was highest in the high
      water stirring treatment, but based on molecular weight, xylanase action on
      solubilised AX was similar as in the extrusion-aided process. Pre-mixing by
      extrusion enabled efficient enzyme action at low water content without the
      requirement for continuous mixing, probably due to the enhanced diffusion by the
      formation of a continuous mass in the extruder. 

PMID- 24103645
TI  - Kinetics of levulinic acid and furfural production from Miscanthus * giganteus.
AB  - This study investigated the kinetics of acid hydrolysis of the cellulose and
      hemicellulose in Miscanthus to produce levulinic acid and furfural under mild
      temperature and high acid concentration. Experiments were carried out in an 8L
      batch reactor with 9%-wt. biomass loading, acid concentrations between 0.10 and
      0.53 M H2SO4, and at temperatures between 150 and 200 degrees C. The
      concentrations of xylose, glucose, furfural, 5-hydroxymethylfurfural and
      levulinic acid were used in two mechanistic kinetic models for the prediction of
      the performance of ideal continuous reactors for the optimisation of levulinic
      acid and the concurrent production of furfural. A two-stage arrangement was found
      to maximise furfural in the first reactor (PFR - 185 degrees C, 0.5M H2SO4, 27.3%
      mol). A second stage leads to levulinic acid yields between 58% and 72%-mol at
      temperatures between 160 and 200 degrees C.

PMID- 24103646
TI  - Role of circulating cell-free DNA levels in patients with severe preeclampsia and
      HELLP syndrome.
AB  - BACKGROUND: Increased plasma levels of circulating cell-free DNA (c-f DNA) have
      been recently described in diseases related to ischemia and/or hypoxia.
      Preeclampsia (PCL) is a hypertensive disorder of pregnancy, of unknown origin,
      where a defective placentation resulting in placental ischemia plays an important
      role. HELLP syndrome (haemolysis, elevated liver enzymes, and low platelet count)
      is the most serious form of PCL. The origin of the disease is unknown, and there
      are no markers to help us to make an early diagnosis of disease or to predict
      patients who are at risk of suffering serious complications. METHODS: We measured
      circulating c-f DNA levels in a group of control pregnant women (n = 20),
      patients with mild PCL (n = 9), patients with severe PCL (n = 24), and patients
      with HELLP syndrome (n = 8). RESULTS: Values of circulating c-f DNA were 333.59
      +/- 64.3 ng/ml in control subjects; 635.11 +/- 111.7 ng/ml in patients with mild
      PCL; 1,264.63 +/- 127.1 ng/ml in patients with severe PCL, and 1,595.95 +/- 269.8
      ng/ml in patients with HELPP syndrome. (P < 0.0001). Values of c-f DNA >950 ng/ml
      had a sensitivity and specificity for detecting severe PCL and/or HELLLP syndrome
      of 0.71 and 0.93, respectively. CONCLUSIONS: As far as we know, this is the first
      report of increased c-f DNA levels in HELLP syndrome. In this preliminary report,
      we have observed a gradual and strong relation between c-f DNA levels and range
      of severity of PCL, with it the highest in patients with HELLP syndrome. Further
      studies are needed for evaluating the utility of this technique in hypertensive
      disorders of pregnancy and, particularly, in HELLP syndrome.

PMID- 24103647
TI  - The JNK inhibitor, SP600125, potentiates the glial response and cell death
      induced by methamphetamine in the mouse striatum.
AB  - This study investigates the effect of the selective Jun NH2-terminal kinase 1/2
      (JNK1/2) inhibitor, (SP600125) on the striatal dopamine nerve terminal loss and
      on the increased interleukin-15 (IL-15) expression and glial response induced by
      methamphetamine (METH). Mice were given repeated low doses of METH (4 mg/kg,
      i.p., three times separated by 3 h) and killed 24 h or 7 d after the last dose.
      SP600125 (30 mg/kg, i.p) was administered 30 min before the last METH injection.
      Results indicate that METH produced dopaminergic axonal neurotoxicity reflected
      as a marked decrease in the striatal density of tyrosine hydroxylase
      immunoreactive (TH-ir) fibres and dopamine transporter-immunoreactivity (DAT-ir)
      24 h after dosing. These effects were not modified by SP600125. This compound
      also failed to prevent the long-term loss of dopamine levels and DAT observed 7 d
      following METH injection. Nevertheless, SP600125 potentiated METH-induced
      striatal cell loss reflected by an increase in Fluoro-Jade immunostaining,
      cleaved capase-3 immunoreactivity and the number of terminal deoxyncleotidyl
      transferase-mediated dUTP nick end labelling (TUNEL) positive cells. In line with
      a deleterious effect of JNK1/2 inhibition, SP600125 increased the astroglial and
      microglial response induced by METH and interfered with drug-induced IL-15
      expression. Together these data indicate that, not only does SP600125 fail to
      protect against the dopaminergic damage induced by METH but also, in fact, it
      potentiates the glial response and the non-dopaminergic striatal cell loss caused
      by the drug. 

PMID- 24103649
TI  - Helicobacter pylori FliD protein is a highly sensitive and specific marker for
      serologic diagnosis of H. pylori infection.
AB  - Screening for H. pylori in large populations continues to be a challenging task,
      since available tests have limited sensitivity and specificity, which, in
      population-based approaches, leads to significant numbers of false positive and
      false negative results. Various H. pylori proteins associated with virulence are
      highly immunogenic and therefore candidates to detect the infection. There are
      currently no defined markers that are recognized in all H. pylori infected
      patients and that do not show cross-reactivity with other bacterial proteins. We
      identified the H. pylori "hook-associated protein 2 homologue", FliD
      (UniProtKB/Swiss-Prot: P96786.4) as a novel marker of infection for serological
      analysis. The H. pylori FliD protein is an essential element in the assembly of
      the functional flagella. However, this virulence factor has not yet been tested
      as a diagnostic marker in serology. For this purpose FliD was recombinantly
      expressed in E. coli, purified by affinity chromatography and gel filtration and
      used to coat ELISA plates or immobilized on nitrocellulose stripes. To evaluate
      its antigenicity we screened a defined panel of patient sera. The recombinant H.
      pylori FliD protein reacted with a high percentage of human sera. Among 318
      samples reported positive by histology, 310 (97.4%) were tested positive by FliD
      Line assay, and 165 out of 170 samples were tested positive by ELISA (97%). We
      could also reconfirm 297 out of 300 (99%) negative sera by Line assay and 73 from
      76 (96%) by ELISA. Taken together, application of FliD in serological diagnosis
      of H. pylori infection presents a high specificity of up to 99% and a sensitivity
      of up to 97%. This makes especially the FliD ELISA a simple, cost effective and
      highly efficient tool to detect H. pylori infection in developing countries where
      prevalence is high and other screening methods are either not available or are
      unaffordable. 

PMID- 24103648
TI  - Monitoring and managing metabolic effects of antipsychotics: a cluster randomized
      trial of an intervention combining evidence-based quality improvement and
      external facilitation.
AB  - BACKGROUND: Treatment of psychotic disorders consists primarily of second
      generation antipsychotics, which are associated with metabolic side effects such
      as overweight/obesity, diabetes, and dyslipidemia. Evidence-based clinical
      practice guidelines recommend timely assessment and management of these
      conditions; however, research studies show deficits and delays in metabolic
      monitoring and management for these patients. This protocol article describes the
      project 'Monitoring and Management for Metabolic Side Effects of Antipsychotics,'
      which is testing an approach to implement recommendations for these practices.
      METHODS/DESIGN: This project employs a cluster randomized clinical trial design
      to test effectiveness of an evidence-based quality improvement plus facilitation
      intervention. Eligible study sites were VA Medical Centers with >=300 patients
      started on a new antipsychotic prescription in a six-month period. A total of 12
      sites, matched in pairs based on scores on an organizational practice survey,
      were then randomized within pairs to intervention or control conditions.Study
      participants include VA employees involved in metabolic monitoring and management
      of patients treated with antipsychotics at participating sites. The intervention
      involves researchers partnering with clinical stakeholders to facilitate
      tailoring of local implementation strategies to address barriers to metabolic
      side-effect monitoring and management. The intervention includes a Design Phase
      (initial site visit and subsequent development of a local implementation plan);
      Implementation Phase (guided by an experienced external facilitator); and a
      Sustainability Phase. Evaluation includes developmental, implementation-focused,
      progress-focused and interpretative formative evaluation components, as well as
      summative evaluation. Evaluation methods include surveys, qualitative data
      collection from provider participants, and quantitative data analysis of data for
      all patients prescribed a new antipsychotic medication at a study site who are
      due for monitoring or management of metabolic side effects during the study
      phases. Changes in rates of recommended monitoring and management actions at
      intervention and control sites will be compared using time series analyses.
      DISCUSSION: Improving monitoring for metabolic side effects of antipsychotics, as
      well as promoting timely evidence-based management when these effects emerge,
      will lead to improved patient safety and long-term outcomes. This article
      discusses key strengths and challenges of the study. TRIAL REGISTRATION:
      NCT01875861.

PMID- 24103650
TI  - Rare-earth-incorporated polymeric vector for enhanced gene delivery.
AB  - Cationic polymer PEI-CyD is doped with Nd by plasma technology to produce the
      gene vector: Nd@PEI-CyD. Luciferase expression and EGFP transfection experiments
      performed in vitro reveal that Nd@PEI-CyD has significantly higher transfection
      efficiency than lipofectamine 2000 and PEI-CyD and the mechanism is studied and
      proposed. The rare-earth element, Nd, stimulates the energy metabolism of cells,
      enhances cell uptake of complexes/pDNA, and regulates the cellular pathways.
      These special features suggest a new strategy involving metal-incorporated non
      viral gene vectors. 

PMID- 24103651
TI  - Specific lipase-responsive polymer-coated gadolinium nanoparticles for MR imaging
      of early acute pancreatitis.
AB  - Currently, available methods for diagnosis of acute pancreatitis (AP) are mainly
      dependent on serum enzyme analysis and imaging techniques that are too low in
      sensitivity and specificity to accurately and promptly diagnose AP. The lack of
      early diagnostic tools highlights the need to search for a highly effective and
      specific diagnostic method. In this study, we synthesized a conditionally
      activated, gadolinium-containing, nanoparticle-based MRI nanoprobe as a
      diagnostic tool for the early identification of AP. Gadolinium
      diethylenetriaminepentaacetic fatty acid (Gd-DTPA-FA) nanoparticles were
      synthesized by conjugation of DTPA-FA ligand and gadolinium acetate. Gd-DTPA-FA
      exhibited low cytotoxicity and excellent biocompatibility when characterized in
      vitro and in vivo studies. L-arginine induced a gradual increase in the intensity
      of the T1-weighted MRI signal from 1 h to 36 h in AP rat models. The increase in
      signal intensity was most significant at 1 h, 6 h and 12 h. These results suggest
      that the Gd-DTPA-FA as an MRI contrast agent is highly efficient and specific to
      detect early AP.

PMID- 24103652
TI  - Cyclodextrins in non-viral gene delivery.
AB  - Cyclodextrins (CDs) are naturally occurring cyclic oligosaccharides. They consist
      of (alpha-1,4)-linked glucose units, and possess a basket-shaped topology with an
      "inner-outer" amphiphilic character. Over the years, substantial efforts have
      been undertaken to investigate the possible use of CDs in drug delivery and
      controlled drug release, yet the potential of CDs in gene delivery has received
      comparatively less discussion in the literature. In this article, we will first
      discuss the properties of CDs for gene delivery, followed by a synopsis of the
      use of CDs in development and modification of non-viral gene carriers. Finally,
      areas that are noteworthy in CD-based gene delivery will be highlighted for
      future research. Due to the application prospects of CDs, it is anticipated that
      CDs will continue to emerge as an important tool for vector development, and will
      play significant roles in facilitating non-viral gene delivery in the forthcoming
      decades. 

PMID- 24103653
TI  - Polycation-functionalized nanoporous silicon particles for gene silencing on
      breast cancer cells.
AB  - Nanoporous silicon particles (pSi), with a pore size in the range of 20-60 nm,
      were modified with polyethyleneimine (PEI) to yield pSi-PEI particles, which were
      subsequently complexed with siRNA. Thus, pSi-PEI/siRNA particles were fabricated,
      with the PEI/siRNA nanocomplexes mainly anchored inside the nanopore of the pSi
      particles. These hybrid particles were used as carriers to deliver siRNA to human
      breast cancer cells. Due to the gradual degradation of the pSi matrix under
      physiological conditions, the PEI/siRNA nanocomplexes were released from the pore
      interior in a sustained manner. Physicochemical characterization revealed that
      the released PEI/siRNA nanocomplexes exhibited well-defined spherical shape and
      narrow particle size distribution between 15 and 30 nm. Gene knockdown against
      the ataxia telangiectasia mutated (ATM) cancer gene showed dramatic gene
      silencing efficacy. Moreover, comprehensive biocompatibility studies were
      performed for the pSi-PEI/siRNA particles both in vitro and in vivo and
      demonstrated that the pSi-PEI particles exhibited significantly enhanced
      biocompatibility. As a consequence, PEI-modified porous silicon particles may
      have substantial potential as safe and effective siRNA delivery systems.

PMID- 24103654
TI  - A high-capacity cell macroencapsulation system supporting the long-term survival
      of genetically engineered allogeneic cells.
AB  - The rapid increase in the number of approved therapeutic proteins, including
      recombinant antibodies, for diseases necessitating chronic treatments raises the
      question of the overall costs imposed on healthcare systems. It is therefore
      important to investigate alternative methods for recombinant protein
      administration. The implantation of genetically engineered cells is an attractive
      strategy for the chronic long-term delivery of recombinant proteins. Here, we
      have developed a high-capacity cell encapsulation system for the implantation of
      allogeneic myoblasts, which survive at high density for at least one year. This
      flat sheet device is based on permeable polypropylene membranes sealed to a
      mechanically resistant frame which confine cells seeded in a tailored biomimetic
      poly(ethylene glycol) (PEG)-based hydrogel matrix. In order to quantitate the
      number of cells surviving in the device and optimize initial conditions leading
      to high-density survival, we implant devices containing C2C12 mouse myoblasts
      expressing a luciferase reporter in the mouse subcutaneous tissue. We show that
      initial cell load, hydrogel stiffness and permeable membrane porosity are
      critical parameters to achieve long-term implant survival and efficacy.
      Optimization of these parameters leads to the survival of encapsulated myogenic
      cells at high density for several months, with minimal inflammatory response and
      dense neovascularization in the adjacent host tissue. Therefore, this
      encapsulation system is an effective platform for the implantation of genetically
      engineered cells in allogeneic conditions, which could be adapted to the chronic
      administration of recombinant proteins. 

PMID- 24103655
TI  - Self-assembled magnetic fluorescent polymeric micelles for magnetic resonance and
      optical imaging.
AB  - Stable and cytocompatible hybrid PEGylated micelles with multimodal imaging
      capabilities are described. The F3O4-encapsulated polymeric micelles composed of
      cores containing magnetic nanoparticles and polyethylene glycol (PEG) shells are
      synthesized by self-assembly of amphiphilic poly(HFMA-co-VBK)-g-PEG copolymers
      and oleic acid stabilized Fe3O4 nanoparticles. The Fe3O4 magnetic nanoparticles
      in the core produce T2-weighted MR imaging functionalities, whereas the small
      fluorescent monomer carbazole in the polymer shell introduces good fluorescent
      properties. The multifunctional micelles exhibit excellent paramagnetic
      properties with the maximum saturation magnetization of 9.61 emu/g and transverse
      relaxivity rate of 157.44 mM(-1) S(-1). In vivo magnetic resonance imaging (MRI)
      studies reveal enhanced contrast between the liver and spleen. Fluorescence
      spectra show characteristic emission peaks from carbazole at 350 nm and 365 nm
      and vivid blue fluorescence can be observed by 2-photon confocal scanning laser
      microscopy (CLSM). In vivo optical imaging demonstrates the unique fluorescent
      characteristics of the Fe3O4-encapsulated polymeric micelles in the liver and
      spleen and the excellent multifunctional properties suggest potential clinical
      use as nanocarriers in magnetic resonance imaging and optical imaging.

PMID- 24103656
TI  - Urogenital schistosomiasis in women of reproductive age and pregnant mothers in
      Kwale County, Kenya.
AB  - Generally, women residing in areas endemic for urinary schistosomiasis may suffer
      from female genital schistosomiasis which is acquired during childhood. The
      objective of this cross-sectional study was to estimate the prevalence and
      intensity of infection of Schistosoma haematobium in women of reproductive age
      (16-45 years) and to investigate whether S. haematobium had any effect on kidney
      function. A total of 394 women of known pregnancy status (158 pregnant and 236
      non-pregnant) were recruited from five villages (known for their high prevalence
      of infection of S. haematobium) in Kwale County. Serum samples were analysed to
      determine levels of urea and creatinine as proxy indicators of kidney function.
      Data revealed that pregnant women did not, on average, have a higher prevalence
      or intensity of infection of urinary schistosomiasis than non-pregnant women.
      During pregnancy, the level of prevalence and intensity of infection of S.
      haematobium was highest in the first trimester (0-13 weeks), dropped in the
      second trimester (14-26 weeks) and rose again in the third trimester (27-40
      weeks). In addition, 24.8% of women were infected with hookworm, while none were
      diagnosed with malaria parasites. Of 250 samples analysed for serum urea and
      creatinine, none had significant levels of pathology, either in pregnant or non
      pregnant women. Despite World Health Organization (WHO) recommendations that
      pregnant women should be treated with praziquantel after the first trimester, in
      practice this has not been the case in many countries, including Kenya. In view
      of this, healthcare providers should be informed to consider treatment of
      pregnant women infected with schistosomiasis during antenatal visits and whenever
      there is mass drug administration as recommended by the WHO. 

PMID- 24103657
TI  - Detection of preclinical neural dysfunction from functional connectivity graphs
      derived from task fMRI. An example from degeneration.
AB  - The early, preferably pre-clinical, identification of neurodegenerative diseases
      is important as treatment will be most successful before substantial neuronal
      loss. Here, we reasoned that functional brain changes as measured using
      functional magnetic resonance imaging (fMRI) will precede neurodegeneration.
      Three independent cohorts of patients with the genetic mutation leading to
      Huntington's Disease (HD) but without any clinical symptoms and matched controls
      performed three different fMRI tasks: Sequential finger tapping engaged the motor
      system, which is primarily affected by HD, whereas a working-memory task and a
      task aiming to induce irritation represented the range of low- and high-level
      cognitive functions also affected by HD. Each diagnostic group of every cohort
      included 11-16 subjects. After segmentation into 76 cortical and 14 subcortical
      regions, we extracted functional connectivity patterns through pairwise
      correlation between the signals in the regions. The resulting coefficients were
      directly embedded as input to a pattern classifier aiming to separate controls
      from gene mutation carriers. Alternatively, graph-theory measures such as degree
      and clustering coefficient were used as features for the discrimination.
      Classification accuracy never outperformed the accuracy of a grouping based on
      parameter estimates from a general-linear model approach or a grouping based on
      features extracted from anatomical images as reported in a previous analysis.
      Despite good within-subject stability between two runs of the same task, a high
      between-subject variability led to chance-level accuracy. These results indicate
      that standard graph-metrics are insufficient to detect subtle disease related
      changes when within-group variability is high. Developing methods that reduce
      variability related to noise should be the focus of future studies. 

PMID- 24103658
TI  - Functional tissue units and their primary tissue motifs in multi-scale
      physiology.
AB  - BACKGROUND: Histology information management relies on complex knowledge derived
      from morphological tissue analyses. These approaches have not significantly
      facilitated the general integration of tissue- and molecular-level knowledge
      across the board in support of a systematic classification of tissue function, as
      well as the coherent multi-scale study of physiology. Our work aims to support
      directly these integrative goals. RESULTS: We describe, for the first time, the
      precise biophysical and topological characteristics of functional units of
      tissue. Such a unit consists of a three-dimensional block of cells centred around
      a capillary, such that each cell in this block is within diffusion distance from
      any other cell in the same block. We refer to this block as a functional tissue
      unit. As a means of simplifying the knowledge representation of this unit, and
      rendering this knowledge more amenable to automated reasoning and classification,
      we developed a simple descriptor of its cellular content and anatomical location,
      which we refer to as a primary tissue motif. In particular, a primary motif
      captures the set of cellular participants of diffusion-mediated interactions
      brokered by secreted products to create a tissue-level molecular network.
      CONCLUSIONS: Multi-organ communication, therefore, may be interpreted in terms of
      interactions between molecular networks housed by interconnected functional
      tissue units. By extension, a functional picture of an organ, or its tissue
      components, may be rationally assembled using a collection of these functional
      tissue units as building blocks. In our work, we outline the biophysical
      rationale for a rigorous definition of a unit of functional tissue organization,
      and demonstrate the application of primary motifs in tissue classification. In so
      doing, we acknowledge (i) the fundamental role of capillaries in directing and
      radically informing tissue architecture, as well as (ii) the importance of taking
      into full account the critical influence of neighbouring cellular environments
      when studying complex developmental and pathological phenomena.

PMID- 24103659
TI  - Prestroke alcohol consumption and smoking are not associated with stroke
      severity, disability at discharge, and case fatality.
AB  - BACKGROUND: Heavy alcohol consumption and smoking are known risk factors for
      stroke, but their influence on stroke severity and outcome may also be important.
      We tested if alcohol consumption and smoking relate to initial stroke severity,
      disability at discharge from hospital, and outcome at 30 days and at 1 year in
      1049 patients of the Mures-Uzhgorod-Debrecen database. METHODS: Initial stroke
      severity was scored by the National Institutes of Health Stroke Scale. Case
      fatality and the modified outcome scale of the First International Stroke Trial
      were used to assess outcome. We used multiple regression analysis. RESULTS:
      Before their stroke, 24.5% were smokers and 24.7% admitted regular alcohol
      consumption. Neither smoking nor alcohol consumption status was associated with
      initial stroke severity. Case fatalities at discharge, at 30 days, and at 1 year
      were 12.2%, 16.9%, and 28.3%, respectively. Initial stroke severity, hemorrhagic
      subtype, and age in men over 60 years were strong predictors of outcome. We did
      not find significant difference among alcohol consumers and nonconsumers in 30
      day and in 1-year case fatality in all stroke patients and in ischemic stroke
      patients. In hemorrhagic stroke, there was a nonsignificant tendency for higher
      case fatality among alcohol consumers (39.5% versus 26.4%, P > .2, at 30 days and
      48.8% versus 35.8%, P > .2, at 1 year). Smoking did not influence significantly
      the outcome at 30 days and at 1 year. CONCLUSION: Despite being risk factors,
      prestroke smoking and alcohol consumption do not have a significant influence on
      stroke severity and on short- and long-term outcome.

PMID- 24103660
TI  - Carotid artery stiffness in patients with symptomatic carotid artery disease with
      contralateral asymptomatic carotid artery disease and in patients with bilateral
      asymptomatic carotid artery disease: a cine phase-contrast carotid MR study.
AB  - BACKGROUND: Atherosclerosis is a systemic inflammatory disease that may affect
      multiple arterial beds simultaneously. Vascular distensibility is increasingly
      used in the clinical assessment of patients with atherosclerotic disease. In this
      study, we assess distensibility of symptomatic atherosclerotic carotid artery and
      of contralateral asymptomatic side. We also investigate the distensibility of
      bilaterally asymptomatic atherosclerotic carotid arteries using cine phase
      contrast carotid magnetic resonance (MR) imaging. METHODS: Nineteen patients with
      bilateral carotid artery disease underwent cine phase-contrast carotid imaging on
      a 1.5 T MR system. Ten patients had ipsilateral symptomatic carotid artery
      disease and contralateral asymptomatic stenosis. Nine additional patients with
      bilateral asymptomatic carotid artery disease constituted historical control
      group. Cine phase-contrast MR imaging acquired at the common carotid artery,
      maximum luminal stenosis, and internal carotid artery was used to determine
      carotid distensibility bilaterally for carotid arteries in both patient groups.
      RESULTS: Symptomatic carotid arteries were found to be significantly less
      distensible (mean distensibility coefficient [DC] 35.4 +/- 6.12 * 10(-3)/kPa)
      than the contralateral asymptomatic vessels (mean DC 54.4 +/- 7.88 * 10(-3)/kPa,
      P = .03) at the level of the common carotid artery. A similar trend of high
      distensibility for asymptomatic side in the area of maximum stenosis and the
      internal carotid artery was seen, but it was not found to be statistically
      significant. Plaque burden was comparable between the 2 groups at all locations.
      DC was comparable for patients with bilateral asymptomatic carotid artery
      stenoses. Distensibility of bilaterally asymptomatic carotid arteries was greater
      than that of asymptomatic carotid artery contralateral to the symptomatic side.
      CONCLUSIONS: Symptomatic carotid artery is stiffer than the contralateral
      asymptomatic side, despite comparable plaque burden. Patients with bilateral
      asymptomatic carotid artery disease have comparable stiffness. Larger studies are
      warranted to further investigate the findings of this MR study.

PMID- 24103661
TI  - Cerebrovascular correlates of sleep disorders-rational and protocol of a door-to
      door survey in rural Coastal Ecuador.
AB  - BACKGROUND: Little is known on the role of sleep disorders in the increased
      prevalence of cerebrovascular diseases in the developing world. AIMS: The aim of
      this study is to assess the prevalence of major sleep disorders in a rural South
      American population and to determine whether these conditions are associated with
      stroke, ischemic heart disease, or with a poor cardiovascular health (CVH).
      DESIGN: Three-phase, population-based, door-to-door survey in Atahualpa. During
      phase I, all residents aged 40 years or older will be screened with validated
      Spanish versions of 5 questionnaires to evaluate major sleep disorders. In phase
      II, neurologists will examine persons suspected of having a sleep disorder and a
      random sample of negative individuals to assess the prevalence of these
      conditions and to validate the accuracy of questionnaires. In phase III, patients
      with a confirmed sleep disorder will undergo nocturnal polysomnography for
      achieving a more specific diagnosis. The occurrence of sleep disorders will be
      correlated with the CVH of the population and with the presence of stroke and
      ischemic heart disease. DISCUSSION: This epidemiologic study may prove cost
      effective in improving sleep conditions of people living in rural areas of
      developing countries and may be used as a model for the evaluation of sleep
      disorders and their cerebrovascular correlates in these populations.

PMID- 24103662
TI  - Disparities in acute stroke severity, outcomes, and care relative to health
      insurance status.
AB  - BACKGROUND: To examine the differences in risk factors and length of hospital
      stay (LOS) between the insured and uninsured stroke patients, identifying the
      root causes of increasing hospital stay. METHODS: Retrospective analysis of
      stroke registry data of acute stroke patients (N = 19,255) was analyzed to
      compare risk factors, severity, outcome, and LOS by insurance status. Chart
      review of patients from a comprehensive stroke center (N = 3290) was studied in
      greater detail for causes of extended length of stay. RESULTS: The uninsured
      patients had poorer control of risk factors and statistically significantly (P <
      .0001) higher initial stroke severity, mortality, and LOS as compared with
      insured patients (3.8 versus 4.5 days, respectively). The increased length of
      stay was largely accounted for by the inability to transfer uninsured patients to
      inpatient rehabilitation settings. CONCLUSION: This study highlights the need for
      public policies that provide funding for both primary stroke prevention and
      poststroke rehabilitation.

PMID- 24103663
TI  - Imaging negative stroke: diagnoses and outcomes in intravenous tissue plasminogen
      activator-treated patients.
AB  - BACKGROUND: Intravenous (IV) Alteplase (tissue plasminogen activator [t-PA])
      improves outcome in patients with acute ischemic stroke. Of those with full
      recovery, some may not have had ischemia. We analyzed the frequency and post
      treatment outcomes of stroke code patients with no imaging evidence of stroke to
      establish the incidence of neuroimaging negative cerebral ischemia (NNCI) and
      stroke mimics treated with t-PA. In addition, we compared these patients with the
      group of stroke patients with imaging evidence of acute stroke to determine
      whether there was a difference in adverse events and functional outcomes.
      METHODS: We included all adult stroke patients treated with IV t-PA within 3
      hours of stroke onset from the University of California, San Diego, Specialized
      Programs of Translational Research in Acute Stroke database through January 2013.
      The imaging positive stroke (IPS) code group comprised patients with neuroimaging
      evidence of acute ischemic stroke, whereas the imaging negative stroke code (INS)
      group included those patients without neuroimaging evidence of acute cerebral
      ischemia. All final diagnoses were reviewed by an adjudicating body. We reviewed
      medical records and neuroimaging; compared discharge diagnosis, 90-day modified
      Rankin Scale (mRS) score, and incidence of intracranial hemorrhage; and adjusted
      for age, admission National Institutes of Health Stroke Scale (NIHSS), prestroke
      mRS, and diabetes in multivariable models. RESULTS: We identified 106 patients,
      74 IPS patients and 32 INS patients, who had similar baseline characteristics,
      except for baseline NIHSS (IPS 12.9 +/- 8.2, INS 8.0 +/- 5.6, P = .002) and
      incidence of cardiac arrhythmias (IPS 32.4%, INS 12.5%, P = .034). The diagnoses
      in the INS group were stroke (23, 72%)-representing NNCI, somatization (6, 19%),
      tumor (1, 3%), seizure (1, 3%), and migraine (1, 3%). All IPS patients were
      diagnosed with acute ischemic stroke. Adjusted for age, baseline NIHSS, prestroke
      mRS, and diabetes, the INS patients had significantly higher rates (odds ratio
      3.04, P = .036) of good functional outcome (90-day mRS score 0-1). Intracerebral
      hemorrhage (ICH) was found in 24% of the IPS patients and was symptomatic in
      6.8%. None of the INS patients had ICH. CONCLUSIONS: Because most INS patients
      were found to have NNCI, which may represent either transient ischemic attack or
      aborted stroke, and there were no intracerebral hemorrhages in the INS group, our
      data support the safety of administering IV t-PA to all patients in whom acute
      ischemic stroke is clinically suspected. We have demonstrated that NNCI patients
      and stroke mimics are common, and future larger scale prospective studies are
      required to delineate the true frequencies of each and to evaluate differences in
      outcomes.

PMID- 24103664
TI  - Noninvasive evaluation of collateral blood flow through circle of Willis in
      cervical carotid stenosis using selective magnetic resonance angiography.
AB  - BACKGROUND: Preoperative assessment of intracranial collateral circulation is
      helpful in predicting cerebral ischemia during surgical procedures for cervical
      internal carotid artery (ICA) stenosis. However, magnetic resonance angiography
      (MRA) and other less-invasive techniques cannot evaluate collateral blood flow
      because these techniques are nonselective. Hence, by using a newly developed
      selective MRA technique, we attempted to visualize collaterals via the circle of
      Willis in patients with ICA stenosis. METHODS: Twelve patients who underwent
      carotid endarterectomy were prospectively examined with a 1.5-T MR scanner. Both
      selective and nonselective MRA were obtained using a 3-dimensional time-of-flight
      technique, with or without a cylindrical saturation pulse that suppresses the
      flow signal from the region of the target ICA. Maximum intensity projection MRA
      images were generated and compared with digital subtraction angiography (DSA)
      images. RESULTS: In all patients, the distal flow signal of the ipsilateral ICA
      was completely suppressed on selective MRA compared with nonselective MRA. In
      addition, collateral blood flow through the anterior and posterior communicating
      arteries was visualized in 5 and 2 patients, respectively. These findings
      corresponded well with the DSA imaging. CONCLUSIONS: Selective MRA techniques can
      readily suppress signals from the distal blood flow of the target artery and
      visualize the presence of collateral flows through the circle of Willis in
      patients with cervical ICA stenosis.

PMID- 24103665
TI  - Reversible cerebral vasoconstriction syndrome with multivessel cervical artery
      dissections and a double aortic arch.
AB  - Reversible cerebral vasoconstriction syndrome (RCVS) has been associated with
      exposure to vasoactive substances and few reports with cervical arterial
      dissections (CADs). We evaluated a 32-year-old woman with history of depression,
      migraines without aura, and cannabis use who presented with a thunderclap
      headache unresponsive to triptans. She was found to have bilateral occipital
      infarcts, bilateral extracranial vertebral artery dissections, bilateral internal
      carotid artery dissecting aneurysms, and extensive distal multifocal segmental
      narrowing of the anterior and posterior intracranial circulation with a "sausage
      on a string-like appearance" suggestive of RCVS. Subsequently, she was found to
      have a distal thrombus of the basilar artery, was anticoagulated, and discharged
      home with no residual deficits. We highlight the potential association of CADs
      and RCVS. The association of RCVS and a double aortic arch has not been
      previously reported. 

PMID- 24103667
TI  - The SAH Score: a comprehensive communication tool.
AB  - BACKGROUND: The Hunt and Hess grade and World Federation of Neurological Surgeons
      (WFNS) scale are commonly used to predict mortality after aneurysmal subarachnoid
      hemorrhage (aSAH). Our objective was to improve the accuracy of mortality
      prediction compared with the aforementioned scales by creating the "SAH score."
      METHODS: The aSAH database at our institution was analyzed for factors affecting
      in-hospital mortality using multiple logistic regression analysis. Scores were
      weighted based on relative risk of mortality after stratification of each of
      these variables. Glasgow Coma Scale (GCS) was subdivided into groups of 3-4
      (score = 1), 5-8 (score = 2), 9-13 (score = 3), and 14-15 (score = 4). Age was
      categorized into 4 subgroups: 18-49 (score = 1), 50-69 (score = 2), 70-79 (score
      = 3), and 80 years or more (score = 4). Medical comorbidities were subdivided
      into none (score = 1), 1 (score = 2), or 2 or more (score = 3). RESULTS: In
      total, 1134 patients were included; all-cause SAH hospital mortality was 18.3%.
      Admission GCS, age, and medical comorbidities significantly affected mortality
      after multivariate analysis (P < .05). Summated scores ranged from 0 to 8 with
      escalating mortality at higher scores (0 = 2%, 1 = 6%, 2 = 8%, 3 = 15%, 4 = 30%,
      5 = 58%, 6 = 79%, 7 = 87%, and 8 = 100%). Positive predictive value (PPV) for
      scores in the range 7-8 was 88.5%, whereas 6-8 was 83%. Negative predictive value
      (NPV) was 94% for range 0-2 and 92% for 0-3. The area under the curve (AUC) for
      the SAH score was .821 (good accuracy), compared with the WFNS scale (AUC .777,
      fair accuracy) and the Hunt and Hess grade (AUC .771, fair accuracy).
      CONCLUSIONS: The SAH score was found to be more accurate in predicting aSAH
      mortality compared with the Hunt and Hess grade and WFNS scale.

PMID- 24103666
TI  - Tracheostomy after severe ischemic stroke: a population-based study.
AB  - BACKGROUND: Stroke can result in varying degrees of respiratory failure. Some
      patients require tracheostomy in order to facilitate weaning from mechanical
      ventilation, long-term airway protection, or a combination of the two. Little is
      known about the rate and predictors of this outcome in patients with severe
      stroke. We aim to determine the rate of tracheostomy after severe ischemic
      stroke. METHODS: Using the Nationwide Inpatient Sample database from 2007 to
      2009, patients hospitalized with ischemic stroke were identified based on
      validated International Classification of Diseases, 9th revision, Clinical
      Modification codes. Next, patients with stroke were stratified based on whether
      they were treated with or without decompressive craniectomy, and the rate of
      tracheostomy for each group was determined. A logistic regression analysis was
      used to identify predictors of tracheostomy after decompressive craniectomy.
      Survey weights were used to obtain nationally representative estimates. RESULTS:
      In 1,550,000 patients discharged with ischemic stroke nationwide, the rate of
      tracheostomy was 1.3% (95% confidence interval [CI], 1.2-1.4%), with a 1.3% (95%
      CI, 1.1-1.4%) rate in patients without decompressive craniectomy and a 33% (95%
      CI, 26-39%) rate in the surgical treatment group. Logistic regression analysis
      identified pneumonia as being significantly associated with tracheostomy after
      decompressive craniectomy (odds ratio, 3.95; 95% CI, 1.95-6.91). CONCLUSIONS:
      Tracheostomy is common after decompressive craniectomy and is strongly associated
      with the development of pneumonia. Given its impact on patient function and
      potentially modifiable associated factors, tracheostomy may warrant further study
      as an important patient-centered outcome among patients with stroke.

PMID- 24103668
TI  - Factors associated with proximal carotid axis occlusion in patients with acute
      stroke and atrial fibrillation.
AB  - BACKGROUND: Patients with atrial fibrillation (AF) are more likely to exhibit
      proximal carotid axis occlusion than those without AF. However, clinical
      characteristics associated with proximal arterial occlusion (PAO) in acute stroke
      patients with AF are not fully known. This study was aimed to elucidate the
      factors correlated with PAO. METHODS: Consecutive patients with acute ischemic
      stroke developed in the middle cerebral artery (MCA) territory and AF who
      underwent magnetic resonance angiography (MRA) within 24 h from onset were
      retrospectively enrolled. Prior users of warfarin were excluded. Patients were
      divided into 3 groups based on the site of arterial occlusion: occlusion at the
      internal carotid artery (ICA), at the horizontal segment of the MCA (M1), and at
      the MCA branch or no identifiable occlusion. Clinical characteristics were
      compared between the 3 groups, and the factors associated with proximal vessel
      occlusion were evaluated with ordinal logistic regression analysis. All variables
      identified on univariable analyses with P values less than .1 were entered into
      the model. RESULTS: A total of 244 patients (124 women, median 80 years old
      [interquartile range 72-87], median National Institutes of Health Stroke Scale
      [NIHSS] score 16 [7-22]) were studied. MRA was performed median 2.7 h (1.5-8.9)
      after stroke onset. Occlusion site was the ICA in 34 patients, M1 in 78, and MCA
      branch or no occlusion in the remaining 132. As the occlusion site was more
      proximal, patients were older and more female, the initial NIHSS score was
      higher, levels of d-dimer and brain natriuretic peptide (BNP) were higher, and
      histories of heart failure and systemic embolism were more common. On
      multivariable ordinal logistic regression analysis, female sex (odds ratio [OR]
      1.83, 95% confidence interval [CI] 1.03-3.26), advanced age (OR 1.37, 95% CI 1.02
      1.84 for every 10 years), history of systemic embolism (OR 14.9, 95% CI 1.41
      157.75), and higher BNP level (OR 1.03, 95% CI 1.01-1.07 for every 100 pg/mL)
      were independent factors associated with the risk of occlusion at more proximal
      arteries. The risk was 2.68-fold higher (95% CI 1.28-5.61) in patients having 2
      of the following factors: female sex, age more than 80 years, systemic embolism,
      and BNP greater than 250 pg/mL; and 4.50-fold (2.11-9.59) higher in those having
      3 or 4 of the 4 factors compared with those without any of these factors.
      CONCLUSIONS: Female sex, advanced age, history of systemic embolism, and higher
      BNP level were independently associated with more proximal carotid axis
      occlusion. Patients with AF having these factors may be prone to have relatively
      large thrombi in the heart.

PMID- 24103669
TI  - Intravenous thrombolysis for ischemic stroke in recurrent oligodendroglioma: a
      case report.
AB  - Data on efficacy and safety of intravenous (IV) thrombolysis with recombinant
      tissue plasminogen activator (rtPA) in patients with acute ischemic stroke (AIS)
      and intracranial neoplasm are lacking. To date, only a handful of case reports
      have been published in the literature addressing the administration of IV rtPA to
      patients with AIS and coexisting brain neoplasms. We present the case of
      successful IV thrombolysis with rtPA for AIS in a patient with oligodendroglioma
      on bevacizumab without hemorrhagic complications. We summarize the published
      cases of thrombolysis in AIS in patients with intracranial neoplasms. 

PMID- 24103670
TI  - Does symptom onset to primary stroke center time goals affect stroke outcome?
AB  - BACKGROUND: Treating acute ischemic stroke (AIS) within 4.5 hours and door-to
      needle time of less than 60 minutes may optimize recovery. It is unknown if onset
      to Primary Stroke Center (PSC) time goals affect outcome. The purpose of this
      study was to examine effects of symptom onset to PSC time goals on outcome.
      METHODS: Analysis included prospectively collected data from the University of
      California San Diego Specialized Program of Treatment Research in Acute Stroke.
      All AIS patients treated with intravenous recombinant tissue plasminogen
      activator were included if treated within 270 minutes, and 90-day modified Rankin
      Scale (mRS) score was known. Primary outcome of the 90-day mRS was analyzed using
      multivariable logistic regression. Good outcome was defined as a 90-day mRS score
      of 0-2. Variables assessed were time from onset to arrival, stroke code,
      neurologic exam, imaging, laboratories, treatment decision, and treatment (by
      quartiles). RESULTS: Two hundred ninety-one patients were included (49.8% female,
      mean age 70.6 +/- 16.1, median National Institutes of Health Stroke Scale 10, SD
      = 8.5). Good outcome occurred in 45% of patients. Significant baseline
      differences included HTN (P <= .001), A fib (P <= .001), prestroke mRS (P <
      .001), and Hispanic ethnicity (P = .011). Comparing good with poor outcome
      groups: mean onset to arrival was 70.6 min versus 62.5 min (P = .129) and mean
      onset to treatment was 140.1 min versus 134.9 min (P = .118). Controlling for
      prespecified covariates, no PSC time goals were significant predictors of the 90
      day outcome. CONCLUSIONS: In our Comprehensive Stroke Center (CSC), onset to PSC
      time goals were not significant predictors of the 90-day outcome. Expedited care
      processes in CSC may compensate for differences in outcome. These results should
      be validated in a larger cohort and in PSCs versus CSCs.

PMID- 24103671
TI  - Dabigatran-related intracerebral hemorrhage resulting in hematoma expansion.
AB  - Warfarin-related intracerebral hemorrhage carries a particularly high risk of
      neurologic deterioration and death because of a high rate of hematoma expansion
      of about 50%. Novel oral anticoagulants (NOACs)--apixaban, dabigatran, and
      rivaroxaban--have a significantly smaller risk of intracerebral hemorrhage (ICH).
      However, two facts make this situation complicated: First, the risk of hematoma
      expansion is unknown for NOACs. Second, there is no specific antidote for neither
      of the NOACs. We present a case that suggests that hematoma expansion may occur
      after NOAC-related ICH.

PMID- 24103672
TI  - Acute foot drop syndrome mimicking peroneal nerve injury: an atypical
      presentation of ischemic stroke.
AB  - Foot drop syndrome is a frequent neurologic condition usually caused by peroneal
      nerve damage. On rare occasions, foot drop may present as the single neurologic
      manifestation of intracranial lesions. We presented a 43-year-old man admitted to
      our hospital with acute weakness in the dorsiflexion of his right foot that
      appeared 3 days before admission. Brain magnetic resonance imaging diffusion
      weighted sequence revealed a small area of restricted diffusion in the left
      frontal cortex. Three months later, his motor deficit had completely improved
      (modified Rankin scale score = 0). To our knowledge, this is the second report of
      sudden isolated foot drop caused by a cortical infarction. 

PMID- 24103673
TI  - Moyamoya disease associated with asymptomatic mosaic Turner syndrome: a rare
      cause of hemorrhagic stroke.
AB  - Moyamoya disease is a rare cerebrovascular anomaly involving the intracranial
      carotid arteries that can present clinically with either ischemic or hemorrhagic
      disease. Moyamoya syndrome, indistinguishable from moyamoya disease at
      presentation, is associated with multiple clinical conditions including
      neurofibromatosis type 1, autoimmune disease, prior radiation therapy, Down
      syndrome, and Turner syndrome. We present the first reported case of an adult
      patient with previously unrecognized mosaic Turner syndrome with acute
      subarachnoid and intracerebral hemorrhage as the initial manifestation of
      moyamoya syndrome. A 52-year-old woman was admitted with a subarachnoid
      hemorrhage with associated flame-shaped intracerebral hemorrhage in the left
      frontal lobe. Physical examination revealed short stature, pectus excavatum,
      small fingers, micrognathia, and mild facial dysmorphism. Cerebral angiography
      showed features consistent with bilateral moyamoya disease, aberrant
      intrathoracic vessels, and an unruptured 4-mm right superior hypophyseal
      aneurysm. Genetic analysis confirmed a diagnosis of mosaic Turner syndrome. Our
      case report is the first documented presentation of adult moyamoya syndrome with
      subarachnoid and intracerebral hemorrhage as the initial presentation of mosaic
      Turner syndrome. It illustrates the utility of genetic evaluation in patients
      with cerebrovascular disease and dysmorphism. 

PMID- 24103674
TI  - High cholesterol levels are associated with improved long-term survival after
      acute ischemic stroke.
AB  - BACKGROUND: Prior statin treatment and high admission cholesterol have been
      associated with favorable outcome after ischemic stroke (IS), a paradox not
      completely explained. The aim of this study was to investigate the effect of
      admission cholesterol levels and the impact of statin treatment on short- and
      long-term survival after IS. METHODS: Consecutive patients admitted in 2006 and
      2010 were included in the study. Total cholesterol of 4.6 mmol/L or more was
      defined as high. Logistic regression analysis was performed to assess predictors
      of 1-month mortality, and Cox proportional hazard regression analysis was applied
      to investigate predictors of long-term mortality. RESULTS: Of 190 patients
      included in the final analysis, 21 (11%) died within 1 month and 61 (32%) died
      during 7 years of observation. Low cholesterol was associated with older age,
      lower blood pressure (BP), presence of angina, and higher risk of death. Three
      month, 1-year, and 5-year survival rates were 100%, 98%, and 84%, respectively,
      in high cholesterol patients, compared with 92%, 87%, and 57% in low cholesterol
      group (P = .0001 with the log-rank test). Mortality risk was increased for
      patients with low cholesterol (hazard ratio: 1.97; 95% confidence interval [CI]:
      1.05-3.69), after adjustment for age and admission National Institutes of Health
      Stroke Scale score. After further adjustment for angina and admission BP, the
      effect of cholesterol on mortality risk was still obvious, yet attenuated (hazard
      ratio: 1.87; 95% CI: .94-3.32). CONCLUSIONS: High admission cholesterol may be
      associated with increased long-term survival after IS. Future studies on the
      temporal profile of cholesterol levels and stroke outcome would be of interest.

PMID- 24103675
TI  - The impact of comprehensive stroke care capacity on the hospital volume of stroke
      interventions: a nationwide study in Japan: J-ASPECT study.
AB  - BACKGROUND: The association between comprehensive stroke care capacity and
      hospital volume of stroke interventions remains uncertain. We performed a
      nationwide survey in Japan to examine the impact of comprehensive stroke care
      capacity on the hospital volume of stroke interventions. METHODS: A questionnaire
      on hospital characteristics, having tissue plasminogen activator (t-PA)
      protocols, and 25 items regarding personnel, diagnostic, specific expertise,
      infrastructure, and educational components recommended for comprehensive stroke
      centers (CSCs) was sent to 1369 professional training institutions. We examined
      the effect of hospital characteristics, having a t-PA protocol, and the number of
      fulfilled CSC items (total CSC score) on the hospital volume of t-PA infusion,
      removal of intracerebral hemorrhage, and coiling and clipping of intracranial
      aneurysms performed in 2009. RESULTS: Approximately 55% of hospitals responded to
      the survey. Facilities with t-PA protocols (85%) had a significantly higher
      likelihood of having 23 CSC items, for example, personnel (eg, neurosurgeons:
      97.3% versus 66.1% and neurologists: 51.3% versus 27.7%), diagnostic (eg, digital
      cerebral angiography: 87.4% versus 43.2%), specific expertise (eg, clipping and
      coiling: 97.2% and 54% versus 58.9% and 14.3%, respectively), infrastructure (eg,
      intensive care unit: 63.9% versus 33.9%), and education (eg, professional
      education: 65.2% versus 20.7%). On multivariate analysis adjusted for hospital
      characteristics, total CSC score, but not having a t-PA protocol, was associated
      with the volume of all types of interventions with a clear increasing trend (P
      for trend < .001). CONCLUSION: We demonstrated a significant association between
      comprehensive stroke care capacity and the hospital volume of stroke
      interventions in Japan.

PMID- 24103676
TI  - Clinical characteristics associated with abnormal diffusion-weighted images in
      patients with transient cerebral ischemic attack.
AB  - BACKGROUND: Precise associations between clinical characteristics of transient
      ischemic attack (TIA) patients and diffusion-weighted imaging (DWI) positivity
      are still controversial. Thus, the purposes of this were to investigate the
      clinical characteristics associated with DWI positivity in patients with TIA and
      to develop a risk score for the prediction of DWI positivity in TIA. METHODS:
      Between April 2008 and June 2011, we retrospectively enrolled consecutive
      patients, who were admitted to our hospital with TIA and underwent DWI within 24
      hours of admission. Patients were divided into a DWI-positive or DWI-negative
      group. The clinical characteristics of the 2 groups were compared, and a DWI
      positivity score was determined for each patient. We calculated the DWI
      positivity score by assigning a point value of 1 to the following factors: blood
      urea nitrogen to serum creatinine (BUN/Cr) ratio greater than 17.5, glucose
      greater than 161 mg/dL, and brain natriuretic peptide (BNP) greater than 55.4
      pg/dL. Values below these cutoffs were given a value of 0, and the 3 point values
      were summed to obtain the final DWI positivity score (from 0 to 3). RESULTS: A
      total of 41 patients (median age = 62 years; 8 women) were enrolled in this
      study. There were 14 (35%) patients with DWI positivity. The median of the BUN/Cr
      ratio, blood glucose, and BNP were significantly higher in the DWI-positive than
      that in the DWI-negative group. As the DWI positivity score increased, there was
      an increased rate of DWI positivity. CONCLUSIONS: Our data indicate that seminal
      scores that included BUN/Cr ratio, glucose, and BNP contributed to DWI positivity
      in TIA patients.

PMID- 24103678
TI  - Mechanistic pharmacology, new developments.

PMID- 24103679
TI  - Label-free receptor assays.

PMID- 24103677
TI  - Increase in the astaxanthin synthase gene (crtS) dose by in vivo DNA fragment
      assembly in Xanthophyllomyces dendrorhous.
AB  - BACKGROUND: Xanthophyllomyces dendrorhous is a basidiomycetous yeast that is
      relevant to biotechnology, as it can synthesize the carotenoid astaxanthin.
      However, the astaxanthin levels produced by wild-type strains are low. Although
      different approaches for promoting increased astaxanthin production have been
      attempted, no commercially competitive results have been obtained thus far. A
      promising alternative to facilitate the production of carotenoids in this yeast
      involves the use of genetic modification. However, a major limitation is the few
      available molecular tools to manipulate X. dendrorhous. RESULTS: In this work,
      the DNA assembler methodology that was previously described in Saccharomyces
      cerevisiae was successfully applied to assemble DNA fragments in vivo and
      integrate these fragments into the genome of X. dendrorhous by homologous
      recombination in only one transformation event. Using this method, the gene
      encoding astaxanthin synthase (crtS) was overexpressed in X. dendrorhous and a
      higher level of astaxanthin was produced. CONCLUSIONS: This methodology could be
      used to easily and rapidly overexpress individual genes or combinations of genes
      simultaneously in X. dendrorhous, eliminating numerous steps involved in
      conventional cloning methods.

PMID- 24103680
TI  - Cell-based assays for kinase drug discovery.

PMID- 24103682
TI  - Use of functional assays to detect and quantify functional selectivity.

PMID- 24103681
TI  - Image-based high-content reporter assays: limitations and advantages.

PMID- 24103683
TI  - Seeking ligand bias: assessing GPCR coupling to beta-arrestins for drug
      discovery.

PMID- 24103684
TI  - G protein-coupled receptor kinases: Specific phosphorylation of 7TM receptors and
      beyond.

PMID- 24103685
TI  - Use of small RNAs for therapeutic gene silencing: risk versus benefit.

PMID- 24103686
TI  - Epigenetics: tools and technologies.

PMID- 24103687
TI  - Epigenetic control of the immune system: histone demethylation as a target for
      drug discovery.

PMID- 24103688
TI  - Uncovering GPCR heteromer-biased ligands.

PMID- 24103689
TI  - An industrial perspective on positive allosteric modulation as a means to
      discover safe and selective drugs.

PMID- 24103690
TI  - Expression and distribution of GnRH, LH, and FSH and their receptors in
      gastrointestinal tract of man and rat.
AB  - BACKGROUND: Gonadotropin-releasing hormone (GnRH), luteinizing hormone (LH), and
      follicle-stimulating hormone (FSH) regulate the reproductive axis. Their analogs
      have been found to influence gastrointestinal activity and enteric neuronal
      survival. The aims of the study were to investigate expression and cellular
      distribution of GnRH, LH, and FSH and their receptors in human and rat
      gastrointestinal tract. METHODS: Bioinformatic analysis of publicly available
      microarray gene expression data and Real-Time PCR mRNA quantification were used
      to study mRNA expression levels of hormones and receptors in human intestinal
      tissue. Full-thickness sections of human ileum and colon, and rat stomach, ileum,
      and colon, were used for immunocytochemistry. Antibodies against human neuronal
      protein HuC/D (HuC/D) were used as general neuronal marker. LH and FSH, and GnRH
      , LH-, and FSH receptor immunoreactive (IR) neurons were evaluated. RESULTS:
      GnRH1 mRNA was detected in both small and large intestine, whereas GnRH2 was
      mainly expressed in small intestine. Approximately 20% of both submucous and
      myenteric neurons displayed LH receptor immunoreactivity in human ileum and
      colon. In rat, 4%-9% of all enteric neurons in fundus and ileum, and 13% of
      submucous neurons and 21% of myenteric neurons in colon were LH receptor-IR.
      Neither mRNA (man) nor the fully expressed proteins (man and rat) of LH and FSH,
      or GnRH and FSH receptors, could be detected. CONCLUSIONS: GnRH1 and GnRH2 mRNA
      are expressed in human intestine. LH receptor-IR enteric neurons are found along
      the entire gastrointestinal tract in both man and rat.

PMID- 24103691
TI  - Activation of intracellular matrix metalloproteinase-2 by reactive oxygen
      nitrogen species: Consequences and therapeutic strategies in the heart.
AB  - Reactive oxygen-nitrogen species play important roles in physiological and
      pathological processes in the heart. This review will focus on the activation of
      matrix metalloproteinases (MMPs) as a result of oxidative stress, and the
      consequences of this on heart function. Although the MMPs are considered to be
      secreted proteases acting on the extracellular matrix to effect tissue
      remodeling, it is now recognized that MMPs also rapidly act on intracellular
      protein targets to cause intracellular protein remodeling. Of the 23 known human
      MMPs, MMP-2 is widely expressed in almost all cell types, is one of the most
      abundant MMPs in cardiac tissue, and recent evidence has revealed mechanisms by
      which it is a bona fide intracellular protein. This review will discuss the
      intracellular localization and novel substrates of MMP-2 within the heart, how
      intracellular protein proteolysis leads to cardiac dysfunction, as well as the
      potential of MMPs inhibitors as therapy for cardiovascular diseases caused by
      enhanced reactive oxygen-nitrogen species.

PMID- 24103692
TI  - Has lung ultrasound an impact on the management of patients with acute dyspnea in
      the emergency department?

PMID- 24103693
TI  - Hypervigilance and avoidance in visual attention in children with social phobia.
AB  - BACKGROUND AND OBJECTIVES: Attentional bias towards threat in socially anxious
      adults is well documented; however, research on this bias in children with social
      phobia is rather scarce. The present study investigates whether the
      hypervigilance-avoidance hypothesis also applies to children with social phobia.
      METHODS: Thirty children (aged 8-12) with social phobia and 43 control children
      participated in an eye-tracking experiment while their attentional distribution
      was recorded. Social anxiety was induced in half of the children before the eye
      tracking task. Stimuli were presented for 3000 ms, and bias scores for initial
      fixations and the time span of attention were assessed. RESULTS: Results
      indicated initial vigilance towards angry faces for all children independent of
      anxiety induction, while hypervigilance (but not avoidance) was only established
      in children with social phobia for angry-neutral face pairs and with social fears
      induced. Self-report measures of anxiety correlated with bias towards threat with
      more pronounced associations occurring in the anxiety induction condition.
      LIMITATIONS: We did not record reaction times simultaneously which limits the
      opportunity to compare our results to some previous studies which focused on this
      variable as an indicator of attention. CONCLUSIONS: Cognitive biases in
      elementary school children (between 8 and 12 years) relate to hypervigilant
      rather than to avoidant information processing. Attentional distribution varies
      over time. Differences between clinical anxious and healthy children seem to be
      modified by anxiety induction, symptom severity and contextual stimuli, such as
      the emotional valence of a face and the context in which the threat stimulus
      appears.

PMID- 24103694
TI  - Regulating medical apps: which ones and how much?

PMID- 24103696
TI  - Emergency doctors exceed their planned hours by 20% or more, survey finds.

PMID- 24103695
TI  - Investigating the fallout of a suicide.

PMID- 24103697
TI  - Public prosecutor explains reasons for not prosecuting doctors who agreed to
      abort female fetuses.

PMID- 24103698
TI  - "Overly prescriptive" targets pose threat to clinical commissioning groups.

PMID- 24103699
TI  - A numerical investigation for robust stability of fractional-order uncertain
      systems.
AB  - This study presents numerical methods for robust stability analysis of closed
      loop control systems with parameter uncertainty. Methods are based on scan
      sampling of interval characteristic polynomials from the hypercube of parameter
      space. Exposed-edge polynomial sampling is used to reduce the computational
      complexity of robust stability analysis. Computer experiments are used for
      demonstration of the proposed robust stability test procedures. 

PMID- 24103700
TI  - The long non-coding RNA HOTAIR indicates a poor prognosis and promotes metastasis
      in non-small cell lung cancer.
AB  - BACKGROUND: The identification of cancer-associated long non-coding RNAs and the
      investigation of their molecular and biological functions are important for
      understanding the molecular biology and progression of cancer. HOTAIR (HOX
      transcript antisense intergenic RNA) has been implicated in several cancers;
      however, its role in non-small cell lung cancer (NSCLC) is unknown. The aim of
      the present study was to examine the expression pattern of HOTAIR in NSCLC and to
      evaluate its biological role and clinical significance in tumor progression.
      METHODS: Expression of HOTAIR was analyzed in 42 NSCLC tissues and four NSCLC
      cell lines by quantitative reverse-transcription polymerase chain reaction (qRT
      PCR). Over-expression and RNA interference (RNAi) approaches were used to
      investigate the biological functions of HOTAIR. The effect of HOTAIR on
      proliferation was evaluated by MTT and colony formation assays, and cell
      migration and invasion were evaluated by transwell assays. Tail vein injection of
      cells was used to study metastasis in nude mice. Protein levels of HOTAIR targets
      were determined by western blot analysis. Differences between groups were tested
      for significance using Student's t-test (two-tailed). RESULTS: HOTAIR was highly
      expressed both in NSCLC samples and cell lines compared with corresponding normal
      counterparts. HOTAIR upregulation was correlated with NSCLC advanced pathological
      stage and lymph-node metastasis. Moreover, patients with high levels of HOTAIR
      expression had a relatively poor prognosis. Inhibition of HOTAIR by RNAi
      decreased the migration and invasion of NSCLC cells in vitro and impeded cell
      metastasis in vivo. HOXA5 levels were affected by HOTAIR knockdown or over
      expression in vitro. CONCLUSIONS: Our findings indicate that HOTAIR is
      significantly up-regulated in NSCLC tissues, and regulates NSCLC cell invasion
      and metastasis, partially via the down-regulation of HOXA5. Thus, HOTAIR may
      represent a new marker of poor prognosis and is a potential therapeutic target
      for NSCLC intervention.

PMID- 24103702
TI  - Management of aquifer recharge in Lebanon by removing seawater intrusion from
      coastal aquifers.
AB  - This study investigates the feasibility of management of aquifer recharge (MAR)
      in Lebanon by designing well barriers to remove seawater intrusion from the
      fractured carbonate aquifers. Groundwater flow and saltwater/freshwater 50% sharp
      interface have been modeled along the coastal area using the Ghyben-Herzberg
      theory. The groundwater flow simulations have been supported by field
      transmissivity estimations and depth measurements carried out on 44 wells during
      2003. Results have shown the seawater intrusion in coastal aquifers at Jieh and
      Damour regions. Three well-injection barriers have been proposed. The water
      volumes for recharge and the barrier positions have been defined by means of
      groundwater flow simulations. MAR can provide a valuable contribution to colloid
      (even pathogen) removal from injectant water, although during water infiltration
      in subsoil the reduction of aquifer permeability causes clogging. A simple new
      model for estimating the soil-rock permeability reduction due to the well
      clogging has been presented. The MAR, including the soil aquifer treatment at
      Damour and Jieh regions, has been studied by considering aquifer transmissivity
      (and soil porosity) reduction caused by clogging. Furthermore, the appropriate
      mixing of the injectant water by using reclaimed water, groundwater and surface
      water can be simulated using the proposed models. The time required to achieve 5%
      of rock permeability reduction at the proposed well barriers ranged from 71 to
      935 d, by changing water quality and flow rate for recharge. This study can
      assist regional governments with water management in areas affected by scarcity
      of freshwater by implementing appropriate well-barrier projects. 

PMID- 24103701
TI  - MicroRNA-mediated mechanism of vitamin D regulation of innate immune response.
AB  - Macrophages play a critical role in innate immune response to protect the host
      from pathogenic microorganisms. Inflammatory response is regulated by negative
      feedback mechanisms to prevent detrimental effects. The SOCS family of proteins
      is key component of the negative feedback loop that regulates the intensity,
      duration and quality of cytokine signaling, whereas miR-155 is a key regulator of
      Toll-like receptor (TLR) signaling that targets SOCS1 in activated macrophages to
      block the negative feedback loop. Recently we showed that 1,25-dihydroxyvitamin D
      (1,25(OH)2D3) modulates innate immune response by targeting the miR-155-SOCS1
      axis. We found that Vdr deletion leads to hyper inflammatory response in mice and
      macrophage cultures when challenged with lipopolysaccharide (LPS), due to miR-155
      overproduction to excessively suppress SOCS1. Using mice with bic/miR-155
      deletion we confirmed that 1,25(OH)2D3 suppresses inflammation and stimulates
      SOCS1 by down-regulating miR-155. Mechanistically 1,25(OH)2D3 down-regulates bic
      transcription by blocking NF-kappaB activation, which is mediated by a kappaB cis
      DNA element identified within the first intron of the bic gene. At the molecular
      level, we demonstrated that VDR inhibits NF-kappaB activation by directly
      interacting with IKKbeta protein. Our studies identified a novel mechanism
      whereby VDR signaling attenuates TLR-mediated inflammation by enhancing the
      negative feedback regulation. This article is part of a Special Issue entitled
      '16th Vitamin D Workshop'. 

PMID- 24103703
TI  - Multi-nutrient supplement improves hormone ratio associated with cancer risk.
AB  - BACKGROUND: Gynecological cancers are among the most common in women and are
      directly related to a variety of hormonal factors. One potential risk factor
      associated with developing a gynecological malignancy is the ratio of two hormone
      metabolites, 2-Hydroxyestrone (2-HE) and 16alpha-Hydroxyestrone (16alpha-HE). A
      number of botanical constituents such as indoles, flavonoids, and resveratrol
      have been shown to have a favorable effect on the metabolic pathways that affect
      this ratio. The present study was designed to evaluate if a multi-nutrient
      supplement containing targeted botanical constituents would affect the 2-HE/16
      alpha-HE ratio in middle-aged women. METHODS: A retrospective analysis was
      performed on 76 female patients (mean age 54 years) who received 2-HE/16 alpha-HE
      ratio assessments at two separate time points. The ratio assessment was part of
      standard care for women who presented with risk indicators associated with a high
      proliferative state. All patients who completed pre and post assessments were
      included. Sixty-five of the patients received a multi-nutrient supplement,
      Lucentia Peak, during the study period. Eleven patients chose not to take the
      supplement, but did receive ratio assessments at similar time points as the
      treatment group, allowing for between group comparisons. Paired t-tests were used
      to compare the changes in the 2-HE and 16alpha-HE measures as well as their
      ratio, both within groups and between groups. RESULTS: The results demonstrated a
      significant increase in the 2-HE/16alpha-HE ratio in the treated group (pre 0.38
      to post 0.57, p<0.0001), and was significantly different (p=0.02) compared to the
      change in the control group (pre 0.65 to post 0.64). This change appears to be
      mediated primarily by an increase in the 2-HE level. Individually, 54 patients
      given Lucentia Peak had increased ratios while 11 patients had a decrease. In the
      control group, 3 patients had an increase in their ratio and 8 patients had a
      decrease. CONCLUSIONS: The results demonstrated that women receiving the Lucentia
      Peak multi-nutrient supplement had significant increases in their 2-HE:16alpha-HE
      ratio, which appears to be mediated primarily by increasing the 2-HE levels.
      These results suggest further research on phytonutrients that might positively
      affect estrogen metabolism is warranted.

PMID- 24103704
TI  - Feasibility and early safety of hybrid coronary revascularisation combining off
      pump coronary surgery through J-hemisternotomy with percutaneous coronary
      intervention.
AB  - AIMS: To assess the procedural feasibility and early safety of hybrid coronary
      revascularisation, combining off-pump left internal mammary artery grafting to
      the left descending coronary artery (LAD) through an inferior J-hemisternotomy
      (JOPCAB) with percutaneous coronary intervention (PCI) of non-LAD lesions.
      METHODS AND RESULTS: A total of 100 patients with multivessel coronary artery
      disease involving LAD were included in this prospective registry. Hybrid
      revascularisation was performed by JOPCAB, either prior to PCI (89%) or following
      PCI (11%). In 96% of the cases, the procedure was carried out according to the
      preoperative strategy and without perioperative (24 hours) major adverse cardiac
      or cerebral events. At one month, we observed no deaths, one stroke and two
      procedure-related myocardial infarctions. Five patients underwent reoperation for
      graft dysfunction, four of whom were identified by angiography without prior
      signs of ischaemia. Reoperation due to bleeding was necessary in six patients,
      and nine patients received red blood cell transfusion. CONCLUSIONS: Our
      prospective registry documented promising procedural feasibility and early safety
      of coronary hybrid revascularisation combining JOPCAB with PCI.
      ClinicalTrials.gov identifier: NCT01496664.

PMID- 24103705
TI  - Scanning electron microscopy of individual nanoparticle bio-markers in liquid.
AB  - We investigated SEM imaging of nanoparticle biomarkers suspended below a thin
      membrane, with the ultimate goal of integrating functional fluorescence and
      structural SEM measurements of samples kept at ambient or hydrated conditions. In
      particular, we investigated how resolving power in liquid SEM is affected by the
      interaction of the electron beam with the membrane. Simulations with the Geant4
      based Monte Carlo scheme developed by Kieft and Bosch (2008) [1] are compared to
      experimental results with suspended nanoparticles. For 20 nm and 50 nm thin
      membranes, we found a beam broadening of 1.5 nm and 3 nm, respectively, with an
      excellent agreement between simulations and experiments. 15 nm Au nanoparticles
      and bio-functionalized core-shell quantum dots can be individually resolved in
      denser clusters. We demonstrated the imaging of single EGF-conjugated quantum
      dots docked at filopodia during cellular uptake with both fluorescence microscopy
      and SEM simultaneously. These results open novel opportunities for correlating
      live fluorescence microscopy with structural electron microscopy.

PMID- 24103706
TI  - Treatment of infected thoracic aortic prosthetic grafts with the in situ
      preservation strategy: a review of its history, surgical technique, and results.
AB  - For cardiothoracic surgeons prosthetic graft infection still represents a
      difficult diagnostic and treatment problem to manage. An aggressive surgical
      strategy involving removal and in situ replacement of all the prosthetic material
      combined with extensive removal of the surrounding mediastinal tissue remains
      technically challenging in any case. Mortality and morbidity rates following such
      a major and risky surgical procedure are high due to the nature of the aggressive
      surgical approach and multi-organ failure typically caused by sepsis. However,
      removal of the infected prosthetic graft in patients who had an operation to
      reconstruct the ascending aorta and/or the aortic arch is not always possible or
      necessary for selected patients according to current alternative treatment
      options. Rather than following the traditional surgical concept of aggressive
      graft replacement nowadays a more conservative surgical approach with in situ
      preservation and coverage of the prosthetic graft by vascular tissue flaps can
      result in a good outcome. In this article, we review the relevant literature on
      this specific topic, particularly in terms of graft-sparing surgery for infected
      ascending/arch prosthetic grafts with special emphasis on staged treatment and
      the use of omentum transposition. 

PMID- 24103707
TI  - Radioactivity measurements in the aquatic environment using in-situ and
      laboratory gamma-ray spectrometry.
AB  - The in-situ underwater gamma-ray spectrometry method is validated by inter
      comparison with laboratory method. Deployments of the spectrometer KATERINA on a
      submarine spring and laboratory measurements of water samples with HPGe detector
      were performed. Efficiency calibrations, Monte Carlo simulations and the Minimum
      Detectable Activity (MDA) estimations were realized. MDAs varied from 0.19 to
      10.4 (lab) and 0.05 to 0.35 (in-situ) Bq/L, while activity concentrations
      differed from 7% (for radon progenies) up to 10% (for (40)K), between the two
      methods. 

PMID- 24103708
TI  - Prone versus supine position for adjuvant breast radiotherapy: a prospective
      study in patients with pendulous breasts.
AB  - PURPOSE: To analyze dosimetric parameters of patients receiving adjuvant breast
      radiotherapy (RT) in the prone versus supine position. METHODS AND MATERIALS:
      Forty-one out of 55 patients with pendulous breasts and candidates for adjuvant
      RT were enrolled in the study after informed consent. They underwent computed
      tomography (CT)-simulation in both prone and supine position. Target and non
      target volumes were outlined on CT images. Prescribed dose was 50 Gy delivered by
      two tangential photon fields followed by 10 Gy electron boost. Target coverage
      and dose homogeneity to clinical target volume (CTV) and planning target volume
      (PTV) were assessed by V95, V105 and V107 and dose to lung, heart and left
      anterior descending coronary artery (LAD) by V5, V10, V20, and mean and maximum
      dose. Data were analyzed by Student's t-test. RESULTS: CTV and PTV coverage was
      significantly better in supine than in prone position. Lung V5, V10, and V20 were
      significantly lower in prone than in supine position. Heart V5, V10, V20, and LAD
      mean and maximum dose, in the 17 patients with left breast tumor, were lower in
      prone than in supine position, but without statistical significance. Based on
      treatment planning data and on treatment feasibility, 29/41 patients (70.7%) were
      treated in prone position. Acute and late toxicities of patients treated in prone
      and in supine position were not statistically different. CONCLUSION: Prone
      position is a favorable alternative for irradiation of mammary gland in patients
      with pendulous breasts and in our series was adopted in 71% of the cases.

PMID- 24103709
TI  - Molecular and morphological characterization of the tapeworm Taenia hydatigena
      (Pallas, 1766) in sheep from Iran.
AB  - Although Taenia hydatigena is one of the most prevalent taeniid species of
      livestock, very little molecular genetic information exists for this parasite. Up
      to 100 sheep isolates of T. hydatigena were collected from 19 abattoirs located
      in the provinces of Tehran, Alborz and Kerman. A calibrated microscope was used
      to measure the larval rostellar hook lengths. Following DNA extraction, fragments
      of cytochrome c oxidase 1 (CO1) and 12S rRNA genes were amplified by the
      polymerase chain reaction method and the amplicons were subjected to sequencing.
      The mean total length of large and small hooks was 203.4 MUm and 135.9 MUm,
      respectively. Forty CO1 and 39 12S rRNA sequence haplotypes were obtained in the
      study. The levels of pairwise nucleotide variation between individual haplotypes
      of CO1 and 12S rRNA genes were determined to be between 0.3-3.4% and 0.2-2.1%,
      respectively. The overall nucleotide variation among all the CO1 haplotypes was
      9.7%, and for all the 12S rRNA haplotypes it was 10.1%. A significant difference
      was observed between rostellar hook morphometry and both CO1 and 12S rRNA
      sequence variability. A significantly high level of genetic variation was
      observed in the present study. The results showed that the 12S rRNA gene is more
      variable than CO1. 

PMID- 24103710
TI  - Different effectiveness of subthalamic deep brain stimulation in Parkinson's
      disease: A comparative cohort study at 1 year and 5 years.
AB  - BACKGROUND/PURPOSE: Subthalamic nucleus deep brain stimulation (STN-DBS) has been
      shown to produce long-term symptom improvement in Parkinson's disease. The aim of
      this study was to identify the target symptoms that show the most improvement at
      1 year and at 5 years after STN-DBS. METHODS: This was a 5-year cohort study of
      41 consecutive patients treated with bilateral STN-DBS. Clinical evaluations were
      performed 1 month prior to surgery and 1 year and 5 years after surgery. The
      outcome measurements at 1 year and 5 years were the changes compared with the
      baseline in Unified Parkinson's Disease Rating Scale (UPDRS) parts I, II, III,
      and IV scores, the Hoehn and Yahr stage, and Schwab and England Activities of
      Daily Living (SEADL) scores in the conditions of off-medication/on-stimulation
      and off-medication/off-stimulation. Further analysis included changes in the
      levodopa equivalent daily dose. RESULTS: When compared to the preoperative
      baseline off-medication condition, significant improvements were observed in the
      UPDRS parts I, II, III, and IV and SEADL (p < 0.001) scores in the off
      medication/on-stimulation condition 1 year after STN-DBS. Five years after STN
      DBS, improvements in UPDRS scores were observed only for parts II, III, and IV (p
      < 0.001). In the off-medication/off-stimulation condition, no significant
      improvement was observed. At 5 years, significant deteriorations were observed in
      scores for the UPDRS part III axial subitem (p = 0.005), UPDRS part I (p =
      0.005), UPDRS part II (p < 0.001), and SEADL (p = 0.001). CONCLUSION: The long
      term effect of STN-DBS on motor function is promising, although the magnitude of
      its effectiveness varied over the 5-year period.

PMID- 24103712
TI  - Measurements of the length and diameter of main bronchi on three-dimensional
      images in Asian adult patients in comparison with the height of patients.
AB  - OBJECTIVE: To measure the length and diameter of the main bronchus using the
      three-dimensional reconstruction images from the spiral chest computerized
      tomography scans in Asian adult patients, and to evaluate the relationship
      between the height of patients and the length and diameter of main bronchi.
      DESIGN: Prospective observational study. SETTING: Academic, tertiary care
      hospital. PARTICIPANTS: Two hundred Asian adults undergoing a chest spiral
      computerized tomography scan. INTERVENTION: No intervention. MEASUREMENTS AND
      MAIN RESULTS: The authors measured the anteroposterior and transverse diameters
      of the mid-portion of the right main bronchus and 2 cm below the carina of the
      left main bronchus. In addition, the length of both main bronchi was also
      measured. The length of the left main bronchus was about 3-4 times greater than
      its right counterpart. The main bronchus of women was oval-shape, with a large
      anteroposterior diameter, but the main bronchus of men was round-shape. There was
      no significant correlation between the measurements of main bronchi and the
      height of patients. CONCLUSIONS: The results showed that there is no direct
      relationship between the length and diameter of main bronchi and the height of
      patients. The height is not the criterion for choosing DLT size. Therefore, the
      authors proposed that 3-D images be used to determine the size of the main
      bronchi. The diameter of main bronchus using the 3-D images can be used to
      determine the optimal size of the DLT in a clinical setting, although further
      studies are needed.

PMID- 24103711
TI  - Reducing mortality in acute kidney injury patients: systematic review and
      international web-based survey.
AB  - OBJECTIVE: To identify all interventions that increase or reduce mortality in
      patients with acute kidney injury (AKI) and to establish the agreement between
      stated beliefs and actual practice in this setting. DESIGN AND SETTING:
      Systematic literature review and international web-based survey. PARTICIPANTS:
      More than 300 physicians from 62 countries. INTERVENTIONS: Several databases,
      including MEDLINE/PubMed, were searched with no time limits (updated February 14,
      2012) to identify all the drugs/techniques/strategies that fulfilled all the
      following criteria: (a) published in a peer-reviewed journal, (b) dealing with
      critically ill adult patients with or at risk for acute kidney injury, and (c)
      reporting a statistically significant reduction or increase in mortality.
      MEASUREMENTS AND MAIN RESULTS: Of the 18 identified interventions, 15 reduced
      mortality and 3 increased mortality. Perioperative hemodynamic optimization,
      albumin in cirrhotic patients, terlipressin for hepatorenal syndrome type 1,
      human immunoglobulin, peri-angiography hemofiltration, fenoldopam, plasma
      exchange in multiple-myeloma-associated AKI, increased intensity of renal
      replacement therapy (RRT), CVVH in severely burned patients, vasopressin in
      septic shock, furosemide by continuous infusion, citrate in continuous RRT, N
      acetylcysteine, continuous and early RRT might reduce mortality in critically ill
      patients with or at risk for AKI; positive fluid balance, hydroxyethyl starch and
      loop diuretics might increase mortality in critically ill patients with or at
      risk for AKI. Web-based opinion differed from consensus opinion for 30% of
      interventions and self-reported practice for 3 interventions. CONCLUSION: The
      authors identified all interventions with at least 1 study suggesting a
      significant effect on mortality in patients with or at risk of AKI and found that
      there is discordance between participant stated beliefs and actual practice
      regarding these topics.

PMID- 24103713
TI  - Effects of early inhaled epoprostenol therapy on pulmonary artery pressure and
      blood loss during LVAD placement.
AB  - OBJECTIVE: Several strategies have been used to reduce the incidence of right
      ventricular failure after left ventricular assist device (LVAD) placement,
      including pulmonary vasodilation. The inhaled prostacyclin, epoprostenol,
      selectively dilates the pulmonary vasculature of ventilated areas of the lung,
      but also has been shown to inhibit platelet aggregation.(1) The authors evaluated
      the impact of early initiation of epoprostenol administration during LVAD
      placement on pulmonary artery pressures, use of vasoactive drugs, and blood loss.
      DESIGN: Retrospective data review. SETTING: Single center, university hospital.
      PARTICIPANTS: A total of 37 consecutive patients undergoing LVAD (HeartMate II)
      placement were included. INTERVENTIONS: In the first group of 23 patients (group
      1), inhaled epoprostenol was not initiated until weaning from cardiopulmonary
      bypass (CPB). In a subsequent group of 14 patients (group 2), inhaled
      epoprostenol was started shortly after induction of anesthesia and continued
      throughout and post-CPB. MEASUREMENTS: Mean and systolic pulmonary artery
      pressures (mPAP, sPAP), vasoactive drugs, as well as hemodynamic parameters,
      blood loss, and use of blood products were recorded at the following time points:
      Baseline (BL), pre-CPB, post-CPB, and during postoperative days (POD) 0, 1, and
      2. Data are presented as mean+/-SD or median [25%, 75%]. RESULTS: Groups did not
      differ in demographic characteristics and comorbidities. BL sPAP (41+/-13 v 46+/
      15 mmHg; p = 0.051) and mPAP (32+/-8 v 34+/-8 mmHg; p = 0.483) values were not
      different between the groups. Systolic and mPAP in group 1 were significantly
      lower in the postoperative period compared with BL (sPAP on POD 0: 34+/-6 mmHg;
      p<0.001; mPAP on POD 0, 1, and 2: 24+/-4 mmHg, 25+/-4 mmHg, 27+/-6 mmHg; p<0.001
      0.003)). In contrast, in group 2, sPAP as well as mPAP were significantly lower
      during weaning from CPB (sPAP: 37+/-8; p = 0.002; mPAP: 28+/-5 mmHg; p = 0.016)
      as well as in the postoperative period (sPAP on POD 0, 1 and 2: 34+/-7, 35+/-7,
      and 37+/-10 mmHg; p<0.001-0.004; mPAP on POD 0, 1, and 2: 24+/-4 mmHg, 25+/-5
      mmHg, 27+/-6 mmHg; p<0.001-0.006). Blood loss on postoperative day 0 was
      significantly lower in group 1 (1646 mL [1137, 2300] v 2915 mL [2335, 6155]; p =
      0.006). Epoprostenol was a significant predictor of blood loss in the regression
      model (p<0.001) but did not predict a change in sPAP. CONCLUSIONS: Inhaled
      prostacyclin reduces sPAP and mPAP in the postoperative period after LVAD
      placement regardless of the timing of initiation. Early initiation seems to
      reduce sPAP as well as mPAP more effectively during the weaning process from CPB.
      However, early initiation is associated with an increased blood loss in the
      immediate postoperative period. The concept of preventively "bathing" the lung in
      prostacyclin should be evaluated critically in a prospective fashion to
      adequately examine this question.

PMID- 24103714
TI  - Mechanism of torrential regurgitation in mitral valve endocarditis: the usual
      chordal rupture-leaflet flail or another more dramatic structural defect?

PMID- 24103716
TI  - Remote ischemic preconditioning reduces cardiac troponin I release in cardiac
      surgery: a meta-analysis.
AB  - OBJECTIVES: To determine whether remote ischemic preconditioning (RIPC) reduces
      myocardial injury, mortality, morbidity, and resource utilization in cardiac
      surgery. DESIGN: Meta-analysis of controlled clinical trials. The primary outcome
      was cardiac troponin I (cTnI) concentrations. Secondary outcomes included cardiac
      troponin T (cTnT) concentrations, myocardial infarction, stroke, renal failure
      requiring hemodialysis, atrial fibrillation, inotropic score, mechanical
      ventilation time, length of intensive care unit stay, length of hospital stay,
      and death. SETTING: University hospitals. PATIENTS: Adult and pediatric patients
      undergoing cardiac surgery, including coronary artery bypass grafting, valve
      procedures, and correction of congenital cardiac anomalies. INTERVENTIONS: Remote
      ischemic preconditioning through limb ischemia. MEASUREMENTS AND MAIN RESULTS:
      Nineteen randomized trials involving 1,235 patients were included in the meta
      analysis. The cTnI concentrations at 6 (or 4-8) hours postoperatively and the
      total cTnI released after surgery showed a statistically significant reduction in
      the RIPC group compared with a control group (weighted mean difference [WMD] 
      2.03 ug/L, 95% confidence interval [CI] -3.25 to -0.82 ug/L, p = 0.001; WMD 
      65.74 ug/L*h, 95% CI -107.88 to -23.61 ug/L*h, p = 0.002, respectively). There
      were no differences in mortality, morbidity, and resource utilization between
      groups. CONCLUSIONS: Current evidence suggests that RIPC reduces cardiac troponin
      I release in patients undergoing cardiac surgery. The clinical significance of
      these observations merits further investigation.

PMID- 24103715
TI  - Perioperative conduction disturbances after transcatheter aortic valve
      replacement.
AB  - Cardiac conduction disturbances after transcatheter aortic valve replacement
      (TAVR) are common and important. The risk factors and outcome effects of atrial
      fibrillation after TAVR recently have been appreciated. The paucity of clinical
      trials has resulted in the absence of clinical guidelines for the management of
      this important arrhythmia in this high-risk patient population. Given this
      evidence gap and clinical necessity, it is likely that clinical trials in the
      near future will be designed and implemented to address these issues. Prompt
      recognition and proper management of atrioventricular block remain essential in
      the management of patients undergoing TAVR, because heart block of all types is
      common and may require permanent pacemaker implantation. The current evidence
      base has described the incidence, risk factors, and current outcomes of this
      conduction disturbance in detail. As the practice of TAVR evolves and novel valve
      prostheses are developed, a focus on minimizing damage to the cardiac conductive
      system remains paramount. It remains to be seen how the next generation of TAVR
      prostheses will affect the incidence, risk factors, and clinical outcomes of
      associated conduction disturbances. 

PMID- 24103718
TI  - Medium-sized molecules - Fertile or futile ground for drug discovery?

PMID- 24103717
TI  - Goal-directed coagulation management in the perioperative period of cardiac
      surgery.

PMID- 24103719
TI  - Methods for the synthesis of macrocycle libraries for drug discovery.

PMID- 24103720
TI  - Recombinant approaches to large polyketide molecules as potential drugs.

PMID- 24103721
TI  - Peptide scalpels for site-specific dissection of the DNA-protein interface.

PMID- 24103722
TI  - siRNAs as potential drugs.

PMID- 24103723
TI  - Synthetic host molecules and sequestrants as therapeutic agents.

PMID- 24103724
TI  - Nanobodies - from llamas to therapeutic proteins.

PMID- 24103725
TI  - "Until the trial is complete you can't really say whether it helped you or not,
      can you?": exploring cancer patients' perceptions of taking part in a trial of
      acupressure wristbands.
AB  - BACKGROUND: Nested qualitative studies within clinical trials provide data on
      patients' experiences of receiving trial interventions and can inform and improve
      trial designs. The present study explored patients' experiences of participating
      in a randomised controlled trial of acupressure wristbands for chemotherapy
      related nausea. METHODS: A randomised three-group sham-controlled trial was
      carried out to evaluate the effectiveness of acupressure wristbands in the
      management of chemotherapy-related nausea. A convenience sample of 26 patients
      volunteered to participate in a qualitative study to explore their experiences of
      using acupressure wristbands, and taking part in the clinical trial. Participants
      were recruited from each of the three UK geographical sites from which the trial
      was conducted: Manchester, Liverpool and Plymouth. In-depth semi-structured
      interviews were conducted with the participants in their own homes or other
      location convenient for participating patients. Interviews were audio-taped,
      transcribed verbatim and analysed using Framework methodology. RESULTS: The main
      motivational factors influencing participants to take part in the trial were a
      desire to 'give something back' and limit their own experience of nausea.
      Participants were largely satisfied with the organisation and running of the
      acupressure wristband trial. Many participants experienced positive outcomes as a
      result of taking part in the trial. Lapses in memory, or poor health as a result
      of their chemotherapy treatment, led to some participants failing to complete
      trial paperwork on designated days. Two sham wristband participants reported
      wearing the bands inappropriately resulting in pressure being applied to the
      acupoint. Almost all of the participants interviewed had only experienced mild
      nausea or vomiting during the trial. Participants were pragmatic on the extent to
      which the wristbands were responsible for this lack of nausea and vomiting during
      the trial. However, many participants, including some patients receiving sham
      acupressure, believed the wristbands to have had a positive impact on their
      nausea and vomiting; there was a perception that the wristbands were, at least in
      part, responsible for the lack of nausea and vomiting they had experienced.
      CONCLUSIONS: Participants perceive acupressure wristbands as reducing the level
      of nausea and vomiting experienced during chemotherapy treatment. Reports that
      some participants wore wristbands inappropriately, and/or delayed completion of
      trial paperwork could represent confounding variables and have implications for
      the trial results, and the design of clinical trials within the field of cancer.

PMID- 24103726
TI  - Developing a semantically rich ontology for the biobank-administration domain.
AB  - BACKGROUND: Biobanks are a critical resource for translational science. Recently,
      semantic web technologies such as ontologies have been found useful in retrieving
      research data from biobanks. However, recent research has also shown that there
      is a lack of data about the administrative aspects of biobanks. These data would
      be helpful to answer research-relevant questions such as what is the scope of
      specimens collected in a biobank, what is the curation status of the specimens,
      and what is the contact information for curators of biobanks. Our use cases
      include giving researchers the ability to retrieve key administrative data (e.g.
      contact information, contact's affiliation, etc.) about the biobanks where
      specific specimens of interest are stored. Thus, our goal is to provide an
      ontology that represents the administrative entities in biobanking and their
      relations. We base our ontology development on a set of 53 data attributes called
      MIABIS, which were in part the result of semantic integration efforts of the
      European Biobanking and Biomolecular Resources Research Infrastructure (BBMRI).
      The previous work on MIABIS provided the domain analysis for our ontology. We
      report on a test of our ontology against competency questions that we derived
      from the initial BBMRI use cases. Future work includes additional ontology
      development to answer additional competency questions from these use cases.
      RESULTS: We created an open-source ontology of biobank administration called
      Ontologized MIABIS (OMIABIS) coded in OWL 2.0 and developed according to the
      principles of the OBO Foundry. It re-uses pre-existing ontologies when possible
      in cooperation with developers of other ontologies in related domains, such as
      the Ontology of Biomedical Investigation. OMIABIS provides a formalized
      representation of biobanks and their administration. Using the ontology and a set
      of Description Logic queries derived from the competency questions that we
      identified, we were able to retrieve test data with perfect accuracy. In
      addition, we began development of a mapping from the ontology to pre-existing
      biobank data structures commonly used in the U.S. CONCLUSIONS: In conclusion, we
      created OMIABIS, an ontology of biobank administration. We found that basing its
      development on pre-existing resources to meet the BBMRI use cases resulted in a
      biobanking ontology that is re-useable in environments other than BBMRI. Our
      ontology retrieved all true positives and no false positives when queried
      according to the competency questions we derived from the BBMRI use cases.
      Mapping OMIABIS to a data structure used for biospecimen collections in a medical
      center in Little Rock, AR showed adequate coverage of our ontology.

PMID- 24103727
TI  - Congenital heart disease in 37,294 births in Tunisia: birth prevalence and
      mortality rate.
AB  - AIM: To investigate the previously unknown birth incidence, treatment, and
      mortality of children with congenital heart disease in Tunisia. METHODS: We
      undertook a retrospective review of medical records of all patients who were born
      in 2010 and 2011, and were diagnosed in Sfax (Tunisia) with congenital heart
      defect. RESULTS: Among 37,294 births, 255 children were detected to have
      congenital heart disease, yielding a birth incidence of 6.8 per 1000. The most
      frequently occurring conditions were ventricular septal defects (31%), ostium
      secundum atrial septal defects (12.9%), and pulmonary valve abnormalities (12%).
      Coarctation of the aorta, tetralogy of Fallot, univentricular physiology,
      pulmonary atresia with ventricular septal defect, and transposition of the great
      arteries were found in 4.3%, 6.2%, 3.4%, 2.7%, and 2.7%, respectively. During the
      follow-up of 1 year, 23% of the children died. About three-quarters of those
      deaths happened before surgery. CONCLUSION: The present study is in line with the
      general estimates in the world. It has revealed a high case of mortality among
      the patients awaiting corrective surgery. These children need more facilities.

PMID- 24103728
TI  - High throughput colorimetric assay for rapid urease activity quantification.
AB  - A novel high throughput colorimetric urease activity assay was compared to the
      Nessler method. The new method employs phenol red to determine the urease
      activity. This method reduces significantly sample processing time and allows
      real-time investigations. This method is rapid, sensitive, easy, cost-effective,
      and does not use any toxic chemical reagents. 

PMID- 24103729
TI  - Novel 5-aryloxypyrimidine SEN1576 as a candidate for the treatment of Alzheimer's
      disease.
AB  - Prefibrillar assembly of amyloid-beta (Abeta) is a major event underlying the
      development of neuropathology and dementia in Alzheimer's disease (AD). This
      study determined the neuroprotective properties of an orally bioavailable Abeta
      synaptotoxicity inhibitor, SEN1576. Binding of SEN1576 to monomeric Abeta 1-42
      was measured using surface plasmon resonance. Thioflavin-T and MTT assays
      determined the ability of SEN1576 to block Abeta 1-42-induced aggregation and
      reduction in cell viability, respectively. In vivo long-term potentiation (LTP)
      determined effects on synaptic toxicity induced by intracerebroventricular
      (i.c.v.) injection of cell-derived Abeta oligomers. An operant behavioural
      schedule measured effects of oral administration following i.c.v. injection of
      Abeta oligomers in normal rats. SEN1576 bound to monomeric Abeta 1-42, protected
      neuronal cells exposed to Abeta 1-42, reduced deficits in in vivo LTP and
      behaviour. SEN1576 exhibits the necessary features of a drug candidate for
      further development as a disease modifying treatment for the early stages of AD
      like dementia. 

PMID- 24103730
TI  - The safety and efficacy of midlines compared to peripherally inserted central
      catheters for adult cystic fibrosis patients: a retrospective, observational
      study.
AB  - BACKGROUND: Intravenous antibiotics are the cornerstone of treatment for patients
      with cystic fibrosis (CF). Midlines are a type of vascular access device (VAD)
      used exclusively in one treatment facility within Australia, most other centres
      use peripherally inserted central catheters (PICCs). OBJECTIVE: To ascertain the
      safety and efficacy of midlines for CF patients receiving intravenous
      antibiotics. DESIGN: Retrospective observational. SETTING: A large, major
      metropolitan teaching hospital in Adelaide, South Australia. PARTICIPANTS: Adult
      patients with a diagnosis of CF, who had a PICC or midline inserted for the
      commencement of antibiotic therapy during the period 2004-2010 to treat a
      respiratory exacerbation. METHODS: Medical records and hospital reports were used
      to record rates of adverse events and unexpected removal of VADs. The primary
      outcome was a composite measure of adverse events (catheter-related blood stream
      infection, deep vein thrombosis, occlusion, pain, infiltration, bleeding,
      phlebitis, catheter leakage and dislodgement) and whether the VAD was removed
      unexpectedly. RESULTS: There were 231 midlines and 97 PICCs inserted into 64
      patients (39 male and 25 female; age range 18-47 years old). Presented as per
      1000 VAD days, patients with PICCs and midlines had similar rates of adverse
      events (14 and 11 adverse events per 1000 VAD days, respectively). Unexpected
      removal was higher for patients with midlines (6.90 per 1000 VAD days) than for
      PICCs (2.89 per 1000 VAD days). Incident rate ratios (IRRs) showed that patients
      with midlines and PICCs had similar rates of adverse events (IRR 1.18, P=0.617,
      CI 0.62-2.22) although the removal rate of patients with midlines was twice that
      of patients with PICCs (IRR 2.24, P=0.079, CI 0.91-5.56). As an absolute risk
      there were only 4.09 more cases of removal for patients with midlines per 1000
      VAD days than those with PICCs. CONCLUSIONS: Midlines may be an alternative to
      PICCs for adult CF patients although further research is required with a larger
      sample size to enable definitive conclusions.

PMID- 24103731
TI  - Sustained reduction of alloantibody secreting plasma cells and donor specific
      antibody with proteasome inhibition in mice.
AB  - The long-lived plasma cells, which develop after alloantigen sensitization,
      produce donor specific alloantibodies (DSAs) that generate a positive serum cross
      match and preclude transplantation. Bortezomib, a proteasome inhibitor, is being
      investigated in clinical desensitization protocols, however preclinical studies
      in a transplant model are nonexistent. We hypothesized that sustained treatment
      with only a proteasome inhibitor would eliminate plasma cells and reduce DSA over
      time. Cardiac allografts were transplanted into murine recipients. Eight weeks
      after allograft rejection the proteasome inhibitor, bortezomib, was injected
      intravenously twice weekly for 60 days. Serum alloantibody responses were assayed
      using flow cross-match. Total and alloreactive plasma cell numbers were
      enumerated using flow cytometry and ELISPOT. All recipients of cardiac allografts
      rejected their graft promptly within 16 days and demonstrated alloantibody by
      flow cross-match. DSA was sustained in the control mice while mice treated with
      bortezomib had sustained elimination of DSA and a marked reduction in plasma cell
      population. Also, bortezomib was associated with an increased level of BLyS.
      Within a murine model, proteasome inhibition can eliminate alloantibody secreting
      plasma cells, and reduce alloantibody. Cessation of bortezomib is not associated
      with return of DSA.

PMID- 24103732
TI  - Effect of novel proteasome and immunoproteasome inhibitors on dendritic cell
      maturation, function, and expression of IkappaB and NFkappaB.
AB  - Dendritic cells (DC) play a central role in the pathophysiology of graft versus
      host disease (GvHD). Their antigen presenting capacity is nuclear factor kappaB-
      (NF-kappaB) dependent. Consequently, DC have emerged as a potential target for
      the prevention of GvHD and clinical trials with bortezomib are underway. We
      explored the activity of novel proteasome and immunoproteasome inhibitors on
      healthy volunteer peripheral blood DC. After incubation with the drug or drug
      combination, DC were stimulated with lipopolysaccharide, stained for maturation
      surface markers and then analyzed by flow cytometry. We found that the different
      molecule(s) inhibited DC maturation marker expression to variable degrees, with
      the constitutive proteasome-selective agent being the least active. In a DC and
      allogeneic CD4+ mixed lymphocyte reaction, DC incubation with the studied
      proteasome and immunoproteasome inhibitor(s), impeded T cell proliferation as
      measured by BrDU incorporation. Finally, we found that DC incubation with the
      drug(s) enhanced IkappaB expression and that oprozomib inhibited NF-kappaB
      expression. We concluded that based on its activity and oral bioavailability,
      oprozomib merits further investigation in an animal GvHD prevention model. We
      also suggest that altering IkappaB and NF-kappaB expressions may, in DC,
      represent a new mechanism of action of proteasome and immunoproteasome
      inhibitors. 

PMID- 24103733
TI  - Inhibiting cardiac allograft rejection with interleukin-35 therapy combined with
      decitabine treatment in mice.
AB  - BACKGROUND: Regulatory T (Treg) cells play a pivotal role in the maintenance of
      transplantation tolerance. It is of great interest to induce allograft tolerance
      mediated by regulatory CD4(+)CD25(+) T cells. METHODS: Here we investigated the
      effect of hydrodynamic IL-35-expressing plasmid injection in combination with a
      methyltransferase inhibitor (decitabine) on immune function and transplantation
      tolerance in mice. RESULTS: We showed that IL-35 and decitabine stimulated the
      proliferation of CD4(+)CD25(+) Tregs and suppressed CD8(+) T cell proliferation
      in an allogenic mixed lymphocyte culture in vitro. IL-35 gene therapy and
      decitabine administration prolonged the survival of the transplanted heart in the
      heterotopic abdominal heart transplantation model in mice. CONCLUSIONS: The
      possible mechanism through which IL-35 and decitabine treatment increased the
      survival of graft tissues is to enhance the proliferation of CD4(+)CD25(+) Treg
      cells and suppress the generation and function of effector T cells. Thus, IL-35
      gene therapy combined with decitabine provides a novel approach to induce
      transplantation tolerance.

PMID- 24103734
TI  - Cyanuric chloride/sodium borohydride: a new reagent combination for reductive
      opening of 4,6-benzylidene acetals of carbohydrates to primary alcohols.
AB  - In the first such example, NaBH4 in combination with cyanuric chloride (TCT) has
      been used to obtain 6-hydroxy-4-benzyl ether derivatives from 4,6-benzylidene
      acetals of carbohydrates. The nature of hydride donor determines the
      regioselectivity of acetal opening. High regioselectivity, scope for using a
      broad range of substrates, functional group tolerance, mild reaction conditions,
      easy handling process, inexpensive reagents and wide application mark the
      benefits of the newly developed reagent system. 

PMID- 24103735
TI  - Critical care rehabilitation trials: the importance of 'usual care'.
AB  - Denehy and colleagues conducted a novel randomized controlled trial evaluating a
      rehabilitation intervention starting in the ICU and continuing through the
      outpatient setting, with 1 year longitudinal follow-up. While the intervention
      did not demonstrate improved patient outcomes, this study illustrates important
      issues regarding 'usual care' control groups in clinical trials. 

PMID- 24103736
TI  - The wild boar (Sus scrofa Linnaeus, 1758) as secondary reservoir of Fasciola
      hepatica in Galicia (NW Spain).
AB  - Fasciolosis is an emerging or reemerging human and animal disease in numerous
      parts of the world. In Galicia (NW, Spain), the wild boar (Sus scrofa) is the
      main wild ungulate in terms of abundance and distribution. Its population has
      continuously increased over the past decades and this population growth has been
      accompanied by a reduction of habitats, so that the wild boar populations
      encroach more and more frequently onto agricultural lands. The increase of the
      interface area between livestock and the wild boars frequently involves the
      sharing of pastures and water sources, so that the circulation of common
      pathogens is propitiated. This is the first report concerning the importance of
      the wild boar as a possible reservoir of Fasciola hepatica infection in Spain.
      Livers from 358 hunted wild boars were analyzed showing that 11.2% were
      parasitized by F. hepatica, with burdens ranging from 1 to 14 flukes (mean=2.3).
      Fecal analysis demonstrated that 40.0% of parasitized animals shed F. hepatica
      eggs with a mean excretion of 6.1 eggs per gram of feces (epg). The presence of
      coproantigens analyzed by MM3-COPRO ELISA was positive in 62.9% of infected wild
      boars. After incubation, the percentage of hatched eggs ranged between 41.0% and
      90.0% suggesting that the wild boar is very likely to contribute to the
      environmental contamination with viable parasite eggs. Comparative morphometric
      data were obtained using a computer image analysis system (CIAS) on the basis of
      standardized measurements. F. hepatica from cattle, sheep and wild boars from the
      same geographical area presents a similar body development and gravidity. Our
      study shows for the first time that the F. hepatica uterus from the wild boar
      presents an intermediate size between that found in primary reservoir hosts such
      as cattle and sheep, i.e., the individual potential egg output capacity of the
      wild boar does not greatly differ from that detected in Galician livestock. These
      results show that F. hepatica in Galicia has a normal development in wild boars,
      presenting its own characteristics in shape and size in comparison with other
      host species. The high prevalence of infection detected in the wild boar, the
      normal fluke development in the liver, and the possibility of shedding F.
      hepatica eggs capable of embryonating and giving rise to viable miracidia with
      the potential to infect intermediate hosts suggest a possible role of this
      species as a secondary reservoir in this Spanish region.

PMID- 24103737
TI  - Toxoplasma gondii and Neospora caninum seroprevalence in dairy sheep and goats
      mixed stock farming.
AB  - Toxoplasma and Neospora infections are important causes of abortions and economic
      losses in animal production. Mixed stock farming of sheep and goats is a common
      practice in Mediterranean countries and could serve as a suitable model for the
      evaluation of differences between the two animal species regarding parasitic
      infections. In order to investigate the seroprevalence of T. gondii and N.
      caninum among flocks of small ruminants in Greece and to evaluate any prevalence
      difference between sheep and goats kept in mixed flocks, 833 sera samples (458
      sheep and 375 goats) from 50 mixed flocks in different areas of the country were
      examined by ELISA for the detection of specific antibodies. Specific IgG against
      T. gondii were detected in 53.71% and 61.3% and against N. caninum in 16.8% and
      6.9% of the sheep and goats, respectively. Goats had higher Toxoplasma
      seroprevalence than sheep (p<0.05), while sheep had higher Neospora
      seroprevalence than goats (p<0.05). The present study is the first report world
      wide, on the seroprevalence of T. gondii and N. caninum in sheep and goats that
      are kept together in mixed flocks.

PMID- 24103738
TI  - Radiotherapy in langerhans cell histiocytosis - a rare indication in a rare
      disease.
AB  - INTRODUCTION: Langerhans Cell Histiocytosis (LCH) represents a rare benign
      disorder, previously designated as "Histiocytosis X", "Type II Histiocytosis" or
      "Langerhans Cell Granulomatosis". Clinical presentation includes osteolysis,
      ulcerations of skin and soft tissues but also involvement of the CNS is
      described.Because treatment concepts are not well defined the German Cooperative
      Group on Radiotherapy for Benign Diseases performed a retrospective analysis.
      METHODS AND MATERIAL: Eight closely cooperating centres collected patients' data
      of the past 45 years. As study endpoints disease free survival, recurrent
      disease, death and therapy related side effects were defined. RESULTS: A total of
      80 patients with histologically proven LCH were irradiated within the past 45
      years. According to the LCH classification of Greenberger et al. 37 patients had
      stage Ia, 21 patients stage Ib, 13 patients stage II and 9 patients stage IIIb
      and the median age was 29 years. The median Follow up was 54 months (range 9-134
      months). A total of 39 patients had a surgical intervention and 23 patients a
      chemotherapy regimen.Radiation treatment was carried out with a median total dose
      of 15 Gy (range 3-50.4 Gy). The median single fraction was 2 Gy (range 1.8-3
      Gy).Overall, 77% patients achieved a complete remission and 12.5% achieved a
      partial remission. The long-term control rate reached 80%. Within an actuarial
      overall 5-year survival of 90% no radiogenic side and late effects >=EORTC/RTOG
      II degrees  were observed. CONCLUSION: In the present study a large collective of
      irradiated patients was analysed. Radiotherapy (RT) is a very effective and safe
      treatment option and even low RT doses show sufficient local control.

PMID- 24103739
TI  - Function of dynamic models in systems biology: linking structure to behaviour.
AB  - BACKGROUND: Dynamic models in Systems Biology are used in computational
      simulation experiments for addressing biological questions. The complexity of the
      modelled biological systems and the growing number and size of the models calls
      for computer support for modelling and simulation in Systems Biology. This
      computer support has to be based on formal representations of relevant knowledge
      fragments. RESULTS: In this paper we describe different functional aspects of
      dynamic models. This description is conceptually embedded in our "meaning facets"
      framework which systematises the interpretation of dynamic models in structural,
      functional and behavioural facets. Here we focus on how function links the
      structure and the behaviour of a model. Models play a specific role (teleological
      function) in the scientific process of finding explanations for dynamic
      phenomena. In order to fulfil this role a model has to be used in simulation
      experiments (pragmatical function). A simulation experiment always refers to a
      specific situation and a state of the model and the modelled system (conditional
      function). We claim that the function of dynamic models refers to both the
      simulation experiment executed by software (intrinsic function) and the
      biological experiment which produces the phenomena under investigation (extrinsic
      function). We use the presented conceptual framework for the function of dynamic
      models to review formal accounts for functional aspects of models in Systems
      Biology, such as checklists, ontologies, and formal languages. Furthermore, we
      identify missing formal accounts for some of the functional aspects. In order to
      fill one of these gaps we propose an ontology for the teleological function of
      models. CONCLUSION: We have thoroughly analysed the role and use of models in
      Systems Biology. The resulting conceptual framework for the function of models is
      an important first step towards a comprehensive formal representation of the
      functional knowledge involved in the modelling and simulation process. Any
      progress in this area will in turn improve computer-supported modelling and
      simulation in Systems Biology.

PMID- 24103740
TI  - Psychological correlates of HIV-related symptom distress.
AB  - This investigation sought to determine the association of symptom distress with
      selected psychological factors in HIV-infected persons. Data from a randomized
      controlled trial were used; all subjects who completed baseline data collection
      were included (N = 99). Data packets included these questionnaires: the Perceived
      Stress Scale, HIV-related Symptom Distress Scale, and Profile of Mood State.
      Significant correlations were included in a final regression model. The Perceived
      Stress Scale, total mood disturbance (including the Profile of Mood State
      subscales), self-rated current health, and HIV status were independently
      associated with both frequency of symptoms and symptom distress. Symptom
      frequency, depression, anger, and fatigue retained significance in the final
      regression model. Findings from this study indicated significant associations of
      multiple psychological correlates, suggesting that symptom distress is a complex
      outcome with a multifactorial etiology. Psychological factors such as depression,
      anger, and fatigue contribute to the level of distress experienced with HIV
      related symptoms.

PMID- 24103741
TI  - Nonoccupational postexposure HIV prophylaxis in sexual assault programs: a survey
      of SANE and FNE program coordinators.
AB  - This cross-sectional study describes sexual assault nurse examiner
      (SANE)/forensic nurse examiner (FNE) program practices related to HIV testing,
      nonoccupational postexposure prophylaxis (nPEP), and common barriers to offering
      HIV testing and nPEP. A convenience sample of 174 SANE/FNE programs in the United
      States and Canada was drawn from the International Association of Forensic Nurses
      database, and program coordinators completed Web-based surveys. Three fourths of
      programs had nPEP policies, 31% provided HIV testing, and 63% offered nPEP
      routinely or upon request. Using chi(2) and Fisher's exact tests, a greater
      proportion of Canadian programs had an nPEP protocol (p = .010), provided HIV
      testing (p = .004), and offered nPEP (p = .0001) than U.S.-based programs.
      Program coordinators rated providing pre- and/or posttest counseling and follow
      up as the most important barrier to HIV testing, and medication costs as the most
      important barrier to providing nPEP. Our results indicate HIV-related services
      are offered inconsistently across SANE/FNE programs. 

PMID- 24103742
TI  - Effectiveness of train-the-trainer HIV education: a model from Vietnam.
AB  - As HIV prevention and treatment efforts expand around the globe, local capacity
      building to update and maintain nurses' HIV competence is essential. The purpose
      of this project was to develop and sustain a national network of nurse-trainers
      who could provide ongoing HIV continuing education and training experiences to
      Vietnamese nurses. Over the course of 6 years, 87 nurses received training to
      become HIV trainers; their HIV knowledge increased significantly (p = .001), as
      did teaching self-confidence (p = .001 to .007). The 87 nurses subsequently
      reported training more than 67,000 health care workers. Recipients of train-the
      trainer-led workshops demonstrated increased HIV knowledge (p = .001) and
      increased willingness to provide nursing care for HIV-infected patients (p =
      .001). The program demonstrated that including a substantial amount of
      instruction in pedagogical strategies and experiential learning could enhance
      knowledge transfer, expand education outreach, and contribute to sustainable HIV
      competence among nurses.

PMID- 24103743
TI  - Implementation of PHQ-9 depression screening for HIV-infected patients in a real
      world setting.
AB  - The prevalence of depression is 20%-30% for people living with HIV, and while it
      is associated with poorer adherence to antiretrovirals, it is often unrecognized
      by medical providers. Although it has been challenging for some health care
      settings to develop consistent depression screening mechanisms, it is feasible to
      create screening protocols using the nine-item Patient Health Questionnaire (PHQ
      9). Establishing a depression screening and response protocol is an iterative
      process that involves preparing staff, determining screening frequency, and
      developing procedures for response and appropriate medical record documentation.
      While there are multiple issues and potential challenges during implementation,
      it is possible to incorporate systematic depression screening into HIV primary
      care in a manner that achieves staff buy-in, minimizes patient burden,
      streamlines communication, and efficiently uses the resources available in the
      medical setting. 

PMID- 24103744
TI  - The evolution of HIV education for nurses in Australia.

PMID- 24103745
TI  - Early healing and hearing improvement following type one tympanoplasty using the
      'drum sandwich' technique.
AB  - BACKGROUND: The results of a number of tympanic membrane perforation closure
      techniques have been reported. However, relatively little has been published on
      the 'drum sandwich' technique. METHOD: Retrospective chart review of 123 patients
      undergoing type one tympanoplasty, performed by one surgeon using the drum
      sandwich technique. RESULTS: Ninety-two per cent of perforations were
      successfully closed, and 87 per cent of patients had healed ears and were free
      from aural discharge 6 weeks following surgery. Post-operative hearing data were
      only available for 81 ears. Of these, 58 per cent had closure of the air-bone gap
      to within 10 dB. The mean hearing gain for the group was 10.6 dB. CONCLUSION: The
      drum sandwich technique produces rapid healing of the ear with acceptable hearing
      outcomes. Drum closure rates are comparable with those reported for other
      techniques.

PMID- 24103746
TI  - Trends in the knowledge, attitudes and practices of travel risk groups toward
      prevention of hepatitis B: results from the repeated cross-sectional Dutch
      Schiphol Airport Survey 2002-2009.
AB  - BACKGROUND: Previous studies investigating the travellers' knowledge, attitudes
      and practices (KAP) profile indicated an important educational need among those
      travelling to risk destinations. METHODS: In the years 2002-2009 an annually
      repeated cross-sectional questionnaire-based survey was conducted at the Dutch
      Schiphol Airport with the aim to study trends in KAP of travel risk groups toward
      prevention of hepatitis B. The frequently encountered risk groups last-minute
      travellers, solo-travellers, business travellers, travellers visiting friends and
      relatives (VFR) and elderly travellers were specifically studied. RESULTS: A
      total of 3045 respondents were included in the survey. Travellers to destinations
      with a high risk for hepatitis B had significantly less accurate risk perceptions
      (knowledge) than travellers to low-risk destinations but no differences were
      observed in past risk-taking attitude. Protection rates against hepatitis B were
      significantly higher in travellers to high-risk destinations. There was a
      positive trend over the years in the proportion of travellers to high-risk
      destinations seeking travel health advice. In accordance with this, trend
      analyses also indicated rising protection rates against hepatitis B. No
      significant trends in protection over time were observed for the travel risk
      groups. CONCLUSIONS: The results of this repeated cross-sectional survey suggest
      an annual 10% increase in protection rates against hepatitis B in Dutch
      travellers, both to destinations with a high risk and to destinations with a
      lower risk of hepatitis B, but these trends in protection rates were not observed
      for the travel risk groups to high-risk destinations. The KAP profile of last
      minute travellers and (to a lesser extent) VFRs showed an increased relative risk
      in hepatitis B, irrespective of the travel destination, underlining the need for
      specific targeting of these travel risk groups.

PMID- 24103747
TI  - Synergistic growth inhibition by acyclic retinoid and phosphatidylinositol 3
      kinase inhibitor in human hepatoma cells.
AB  - BACKGROUND: A malfunction of RXRalpha due to phosphorylation is associated with
      liver carcinogenesis, and acyclic retinoid (ACR), which targets RXRalpha, can
      prevent the development of hepatocellular carcinoma (HCC). Activation of PI3K/Akt
      signaling plays a critical role in the proliferation and survival of HCC cells.
      The present study examined the possible combined effects of ACR and LY294002, a
      PI3K inhibitor, on the growth of human HCC cells. METHODS: This study examined
      the effects of the combination of ACR plus LY294002 on the growth of HLF human
      HCC cells. RESULTS: ACR and LY294002 preferentially inhibited the growth of HLF
      cells in comparison with Hc normal hepatocytes. The combination of 1 MUM ACR and
      5 MUM LY294002, in which the concentrations used are less than the IC50 values of
      these agents, synergistically inhibited the growth of HLF, Hep3B, and Huh7 human
      HCC cells. These agents when administered in combination acted cooperatively to
      induce apoptosis in HLF cells. The phosphorylation of RXRalpha, Akt, and ERK
      proteins in HLF cells were markedly inhibited by treatment with ACR plus
      LY294002. Moreover, this combination also increased RXRE promoter activity and
      the cellular levels of RARbeta and p21(CIP1), while decreasing the levels of
      cyclin D1. CONCLUSION: ACR and LY294002 cooperatively increase the expression of
      RARbeta, while inhibiting the phosphorylation of RXRalpha, and that these effects
      are associated with the induction of apoptosis and the inhibition of cell growth
      in human HCC cells. This combination might therefore be effective for the
      chemoprevention and chemotherapy of HCC.

PMID- 24103748
TI  - Ephrin-A1 expression induced by S100A8 is mediated by the toll-like receptor 4.
AB  - The deregulation of Eph/ephrin protein expression has been shown to lead to tumor
      development and progression. Both mRNA and protein expression analyses using
      clinical samples have demonstrated that ephrin-A1 is over-expressed in various
      cancers and positively correlates with a poor prognosis for cancer patients. The
      prognosis of cancer patients depends on metastasis to distant organs. We
      previously demonstrated that ADAM12 metalloproteinase cleaved ephrin-A1 and
      ADAM12-cleaved ephrin-A1 enhanced vascular permeability by degrading VE-cadherin
      and the EphA2 receptor at the plasma membrane. An increase of soluble ephrin-A1
      levels in the serum facilitated tumor cell recruitment to the lungs, which
      resulted in lung metastasis. We also found that ephrin-A1 was overexpressed in
      3LL tumors, a highly metastatic tumor, in mice and TNFalpha, an authentic
      positive regulator of ephrin-A1, was not elevated in the tumors, whereas S100A8
      was. Moreover, S100A8 induced ephrin-A1 expression mediated by the toll-like
      receptor 4 (TLR4). S100A8 is known to be an endogenous ligand for TLR4 and its
      expression was shown to be increased in the lungs at the premetastatic phase.
      Thus, S100A8 and ephrin-A1 contribute to lung metastasis. Therefore, elucidating
      the regulation mechanism of ephrin-A1 overexpression is of importance and may
      lead to the development of therapeutic drugs against tumor growth and metastasis.

PMID- 24103749
TI  - The dual mTORC1 and mTORC2 inhibitor AZD8055 inhibits head and neck squamous cell
      carcinoma cell growth in vivo and in vitro.
AB  - The serine/threonine kinase mammalian target of rapamycin (mTOR) promotes cell
      survival and proliferation, and is constitutively activated in head and neck
      squamous cell carcinoma (HNSCC). Thus mTOR is an important target for drug
      development in this disease. Here we tested the anti-tumor ability of AZD8055,
      the novel mTOR inhibitor, in HNSCC cells. AZD8055 induced dramatic cell death of
      HNSCC lines (Hep-2 and SCC-9) through autophagy. AZD8055 blocked both mTOR
      complex (mTORC) 1 and mTORC2 activation without affecting Erk in cultured HNSCC
      cells. Meanwhile, AZD8055 induced significant c-Jun N-terminal kinase (JNK)
      activation, which was also required for cancer cell death. JNK inhibition by its
      inhibitors (SP 600125 and JNK-IN-8), or by RNA interference (RNAi) alleviated
      AZD8055-induced cell death. Finally, AZD8055 markedly increased the survival of
      Hep-2 transplanted mice through a significant reduction of tumor growth, without
      apparent toxicity, and its anti-tumor ability was more potent than rapamycin.
      Meanwhile, AZD8055 administration activated JNK while blocking mTORC1/2 in Hep-2
      tumor engrafts. Our current results strongly suggest that AZD8055 may be further
      investigated for HNSCC treatment in clinical trials. 

PMID- 24103750
TI  - Analysis of an intronic promoter within Synj2.
AB  - Synj2 (synaptojanin 2) encodes an inositol polyphosphate phosphatase that
      functions in recycling neurotransmitter vesicles and is implicated in
      spermatogenesis. Transcription of Synj2 is thought to occur from one of two
      promoters based on analysis of a variable 5' untranslated region. Clustering all
      known mouse Synj2 transcripts led us to uncover a novel subset of transcripts
      that appears to derive from a region located within intron 7. We identified two
      alternate splice variants emanating from use of this promoter. These alternate
      splice variants manifest developmental stage specificity and somatic versus
      gametic differences in expression. 

PMID- 24103751
TI  - Identification of the proteins required for fatty acid desaturation in zebrafish
      (Danio rerio).
AB  - Zebrafish Delta-5/Delta-6 fatty acid desaturase (Z-FADS) catalyzes the cascade
      synthesis of long-chain polyunsaturated fatty acids (PUFAs), thereby playing a
      pivotal role in several biological processes. In the current study, we report
      that the Z-FADS protein exists in close proximity to certain cytochrome b5
      reductases (CYB5R2 and 3) and elongases (ELOVL2, 4, 5 and 7) on the endoplasmic
      reticulum, as determined using fluorescence microscopy and fluorescence resonance
      energy transfer. HeLa cells co-transfected with zebrafish fads and elovl2, 4, and
      5 produced docosahexaenoic acid (DHA), as detected by gas chromatography. In
      addition, immunofluorescence cytochemistry and Western blot data revealed that Z
      FADS is present in the mitochondria of HeLa cells. Collectively, our results
      implicate that Z-FADS, the sole fatty acid desaturase ever been identified in
      zebrafish, can serve as a universal fatty acid desaturase during lipogenesis. 

PMID- 24103752
TI  - Increased parasite surface antigen-2 expression in clinical isolates of
      Leishmania donovani augments antimony resistance.
AB  - Resistance to sodium antimony gluconate (SAG) is a major cause of therapeutic
      failure in a large proportion of visceral leishmaniasis (VL) cases. Determinants
      of SAG resistance have been widely studied; however, the mechanism operating in
      clinical isolates is poorly understood. In the present study, expression of
      parasite surface antigen-2 (PSA-2) gene was studied in clinical isolates of
      Leishmania donovani comprising of antimony resistant (n=10) and sensitive (n=4)
      parasites. The expression of PSA-2 gene was found to be consistently high in SAG
      resistant clinical isolates (>=1.5-fold) at both transcript and protein level.
      Further, over-expression of PSA-2 in L. donovani isolates (LdPSA-2(++)) resulted
      in conversion of SAG sensitive phenotype to resistant. The LdPSA-2(++) parasites
      showed significantly decreased susceptibility towards SAG (>12-fold),
      amphotericin B (>4-fold) and miltefosine (>2.5-fold). Marked decrease in antimony
      accumulation and enhanced tolerance towards complement mediated lysis was evident
      in LdPSA-2(++) parasites. The study established the role of PSA-2 gene in SAG
      resistance and its potential as a biomarker to distinguish resistant and
      sensitive clinical isolates of L. donovani.

PMID- 24103753
TI  - Caffeic acid phenethyl ester downregulates phospholipase D1 via direct binding
      and inhibition of NFkappaB transactivation.
AB  - Upregulation of phospholipase D (PLD) is functionally linked with oncogenic
      signals and tumorigenesis. Caffeic acid phenethyl ester (CAPE) is an active
      compound of propolis extract that exhibits anti-proliferative, anti-inflammatory,
      anti-oxidant, and antineoplastic properties. In this study, we demonstrated that
      CAPE suppressed the expression of PLD1 at the transcriptional level via
      inhibition of binding of NFkappaB to PLD1 promoter. Moreover, CAPE, but not its
      analogs, bound to a Cys837 residue of PLD1 and inhibited enzymatic activity of
      PLD. CAPE also decreased activation of matrix metalloproteinases-2 induced by
      phosphatidic acid, a product of PLD activity. Ultimately, CAPE-induced
      downregulation of PLD1 suppressed invasion and proliferation of glioma cells.
      Taken together, the results of this study indicate that CAPE might contribute to
      anti-neoplastic effect by targeting PLD1. 

PMID- 24103754
TI  - Antibody against the actin-binding protein depactin attenuates Ca2+ signaling in
      starfish eggs.
AB  - Being present in starfish oocytes, the cofilin/ADF (actin-depolymerizing factor)
      family protein depactin severs actin filaments. Previously, we reported that
      exogenous cofilin microinjected into starfish eggs significantly augmented the
      Ca(2+) release in response to inositol 1,4,5-trisphosphate (InsP3) or fertilizing
      sperm, raising the possibility that intracellular Ca(2+) signaling could be
      modulated by the actin cytoskeleton. In this communication, we have targeted the
      endogenous depactin by use of the specific antibody that was raised against its
      actin-binding domain. The anti-depactin antibody microinjected into the starfish
      oocytes and eggs effectively altered the structure of the actin cytoskeleton, and
      significantly delayed the meiotic progression induced by 1-methyladenine. When
      microinjected into the mature eggs, the anti-depactin antibody markedly reduced
      the amplitude of the Ca(2+) response in a dose-dependent manner, corroborating
      the results of our previous study with cofilin. In addition, the eggs
      microinjected with the anti-depactin antibody displayed reduced rate of
      successful elevation of the fertilization envelope and an elevated tendency of
      polyspermic interaction. Taken together, our data suggest that the actin
      cytoskeleton is implicated not only in meiotic maturation and intracellular
      Ca(2+) signaling, but also in the fine regulation of gametes interaction and
      cortical granules exocytosis. 

PMID- 24103755
TI  - Down-regulation of PERK enhances resistance to ionizing radiation.
AB  - Although, ionizing radiation (IR) has been implicated to cause stress in
      endoplasmic reticulum (ER), how ER stress signaling and major ER stress sensors
      modulate cellular response to IR is unclear. Protein kinase RNA-like endoplasmic
      reticulum kinase (PERK) is an ER transmembrane protein which initiates unfolded
      protein response (UPR) or ER stress signaling when ER homeostasis is disturbed.
      Here, we report that down-regulation of PERK resulted in increased clonogenic
      survival, enhanced DNA repair and reduced apoptosis in irradiated cancer cells.
      Our study demonstrated that PERK has a role in sensitizing cancer cells to IR. 

PMID- 24103756
TI  - Beneficial effects of vildagliptin combined with miglitol on glucose tolerance
      and islet morphology in diet-controlled db/db mice.
AB  - Dipeptidyl peptidase-4 (DPP-4) inhibitors improve glycemic control in patients
      with type 2 diabetes primarily by increasing plasma active glucagon-like peptide
      1 (GLP-1) levels. While various combination therapies based on DPP-4 inhibitors
      have been proposed for treatment of type 2 diabetes, the effects of combination
      therapy of DPP-4 inhibitors and alpha-glucosidase inhibitors on beta-cell
      function are less characterized. We evaluated the effects of long-term treatment
      with vildagliptin, a DPP-4 inhibitor, on metabolic parameters and beta-cell
      function, in combination with miglitol, an alpha-glucosidase inhibitor, in diet
      controlled db/db mice. In this study, 6-week-old male db/db mice were provided
      with standard chow twice a day for 6 weeks. Meal tolerance tests and glucose
      tolerance tests showed that the combination therapy of vildagliptin with
      miglitol, but not each alone, suppressed postprandial glycemic excursion,
      enhanced postprandial active GLP-1 levels and prevented deterioration of glucose
      tolerance in the db/db mice. The combination treatment did not alter beta-cell
      mass, but resulted in preserved expression of glucose transporter 2, Zinc
      transporter 8 and MafA and reduced the number of alpha cells. These results
      suggest that the combination of vildagliptin and miglitol prevents the
      development of overt diabetes in diet-controlled pre-diabetic db/db mice by
      normalizing postprandial glucose and incretin response, and by preserving beta
      cell structure and the expression of factors essential for beta-cell function.

PMID- 24103757
TI  - Interleukin-3 plays dual roles in osteoclastogenesis by promoting the development
      of osteoclast progenitors but inhibiting the osteoclastogenic process.
AB  - Interleukin (IL)-3, a multilineage hematopoietic growth factor, is implicated in
      the regulation of osteoclastogenesis. However, the role of IL-3 in
      osteoclastogenesis remains controversial; whereas early studies showed that IL-3
      stimulates osteoclastogenesis, recent investigations demonstrated that IL-3
      inhibits osteoclast formation. The objective of this work is to further address
      the role of IL-3 in osteoclastogenesis. We found that IL-3 treatment of bone
      marrow cells generated a population of cells capable of differentiating into
      osteoclasts in tissue culture dishes in response to the stimulation of the
      monocyte/macrophage-colony stimulating factor (M-CSF) and the receptor activator
      of nuclear factor kappa B ligand (RANKL). The IL-3-dependent hematopoietic cells
      were able to further proliferate and differentiate in response to M-CSF
      stimulation and the resulting cells were also capable of forming osteoclasts with
      M-CSF and RANKL treatment. Interestingly, IL-3 inhibits M-CSF-/RANKL-induced
      differentiation of the IL-3-dependent hematopoietic cells into osteoclasts. The
      flow cytometry analysis indicates that while IL-3 treatment of bone marrow cells
      slightly affected the percentage of osteoclast precursors in the surviving
      populations, it considerably increased the percentage of osteoclast precursors in
      the populations after subsequent M-CSF treatment. Moreover, osteoclasts derived
      from IL-3-dependent hematopoietic cells were fully functional. Thus, we conclude
      that IL-3 plays dual roles in osteoclastogenesis by promoting the development of
      osteoclast progenitors but inhibiting the osteoclastogenic process. These
      findings provide a better understanding of the role of IL-3 in
      osteoclastogenesis. 

PMID- 24103758
TI  - AMPK regulates K(ATP) channel trafficking via PTEN inhibition in leptin-treated
      pancreatic beta-cells.
AB  - Leptin regulates pancreatic beta-cell excitability through AMP-activated protein
      kinase (AMPK)-mediated ATP-sensitive potassium (KATP) channel trafficking.
      However, the signaling components connecting AMPK to KATP channel trafficking are
      not identified. In this study, we discovered that AMPK inhibits phosphatase and
      tensin homologue (PTEN) via glycogen synthase kinase 3beta (GSK3beta) and this
      signaling pathway is crucial for KATP channel trafficking in leptin-treated
      pancreatic beta-cells. Pharmacologic or genetic inhibition of AMPK or GSK3beta,
      but not casein kinase 2 (CK2), impaired leptin-induced PTEN inactivation and
      thereby KATP channel trafficking. The PTEN mutant lacking both protein and lipid
      phosphatase activity is sufficient to induce KATP channel trafficking without
      leptin. These results present a novel signaling mechanism that underlies leptin
      regulation of KATP channel trafficking in pancreatic beta-cells. Our findings
      assist in gaining a broader perspective on the peripheral action of leptin on
      pancreatic beta-cell physiology and glucose homeostasis. 

PMID- 24103759
TI  - Thyroid hormone negatively regulates CDX2 and SOAT2 mRNA expression via induction
      of miRNA-181d in hepatic cells.
AB  - Thyroid hormones (THs) regulate transcription of many metabolic genes in the
      liver through its nuclear receptors (TRs). Although the molecular mechanisms for
      positive regulation of hepatic genes by TH are well understood, much less is
      known about TH-mediated negative regulation. Recently, several nuclear hormone
      receptors were shown to downregulate gene expression via miRNAs. To further
      examine the potential role of miRNAs in TH-mediated negative regulation, we used
      a miRNA microarray to identify miRNAs that were directly regulated by TH in a
      human hepatic cell line. In our screen, we discovered that miRNA-181d is a novel
      hepatic miRNA that was regulated by TH in hepatic cell culture and in vivo.
      Furthermore, we identified and characterized two novel TH-regulated target genes
      that were downstream of miR-181d signaling: caudal type homeobox 2 (CDX2) and
      sterol O-acyltransferase 2 (SOAT2 or ACAT2). CDX2, a known positive regulator of
      hepatocyte differentiation, was regulated by miR-181d and directly activated
      SOAT2 gene expression. Since SOAT2 is an enzyme that generates cholesteryl esters
      that are packaged into lipoproteins, our results suggest miR-181d plays a
      significant role in the negative regulation of key metabolic genes by TH in the
      liver. 

PMID- 24103760
TI  - 21-Methylpyrenyl-cholesterol stably and specifically associates with lipoprotein
      peripheral hemi-membrane: a new labelling tool.
AB  - Lipoproteins are important biological components. However, they have few
      convenient fluorescent labelling probes currently reported, and their
      physiological reliability can be questioned. We compared the association of two
      fluorescent cholesterol derivatives, 22-nitrobenzoxadiazole-cholesterol (NBD
      Chol) and 21-methylpyrenyl-cholesterol (Pyr-met-Chol), to serum lipoproteins and
      to purified HDL and LDL. Both lipoproteins could be stably labelled by Pyr-met
      Chol, but virtually not by NBD-Chol. At variance with NBD-Chol, LCAT did not
      esterify Pyr-met-Chol. The labelling characteristics of lipoproteins by Pyr-met
      Chol were well distinguishable between HDL and LDL, regarding dializability,
      associated probe amount and labelling kinetics. We took benefit of the pyrene
      labelling to approach the structural organization of LDL peripheral hemi
      membrane, since Pyr-met-Chol-labelled LDL, but not HDL, presented a fluorescence
      emission of pyrene excimers, indicating that the probe was present in an ordered
      lipid micro-environment. Since the peripheral membrane of LDL contains more
      sphingomyelin (SM) than HDL, this excimer formation was consistent with the
      existence of cholesterol- and SM-enriched lipid microdomains in LDL, as already
      suggested in model membranes of similar composition and reminiscent to the well
      described "lipid rafts" in bilayer membranes. Finally, we showed that Pyr-met
      Chol could stain cultured PC-3 cells via lipoprotein-mediated delivery, with a
      staining pattern well different to that observed with NBD-Chol non-specifically
      delivered to the cells. 

PMID- 24103761
TI  - DNA methylation of the BMAL1 promoter.
AB  - We previously analyzed transcriptional regulation of the BMAL1 gene, a critical
      component of the mammalian clock system and found that the BMAL1 gene is
      expressed with circadian oscillation and that its regulatory region is located in
      hypomethylated CpG islands with an open chromatin structure. Here, we found that
      the BMAL1 gene is not expressed with circadian oscillation in CPT-K cells because
      the CpG islands located in the BMAL1 promoter are hypermethylated and that 5-aza
      2'-deoxycytidine (aza-dC) recovered BMAL1 expression. In contrast, CpG islands in
      the PER2 promoter were hypomethylated, the PER2 gene was expressed and aza-dC
      enhanced PER2 gene expression in CPT-K cells. Reporter gene assays showed that
      intracellular transcriptional machinery for the BMAL1 gene is active, suggesting
      that BMAL1 inactivation is caused by DNA methylation and not by malfunctional
      promoter activity. Incubating CPT-K cells with aza-dC also increased CRY1
      expression, whereas CLOCK expression was not altered and the CRY1 promoter was
      unmethylated. These results suggest that aza-dC induces BMAL1 expression via DNA
      demethylation in the BMAL1 promoter and enhances PER2 and CRY1 transcription.
      Finally, aza-dC recovered the circadian oscillation of BMAL1 transcription. These
      results suggest that DNA methylation of the BMAL1 gene is critical for
      interfering with circadian rhythms. 

PMID- 24103762
TI  - Geraniol attenuates alpha-synuclein expression and neuromuscular impairment
      through increase dopamine content in MPTP intoxicated mice by dose dependent
      manner.
AB  - Parkinson's disease (PD) is characterized by progressive loss of dopamine (DA)
      neurons in the nigrostriatal system and by the presence of Lewy bodies (LB),
      proteinaceous inclusions mainly composed of filamentous alpha-synuclein (alpha
      Syn) aggregates. 1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) was adopted
      to generate PD models in C57BL/6 mice. In the present study, we investigated the
      effect of geraniol (GE) against alpha-Syn aggregation on MPTP induced mouse model
      of PD in dose dependant manner. When pretreatment of GE improved neuromuscular
      impairment, TH expressions and decreases alpha-Syn expressions in MPTP
      intoxicated PD mice by dose dependent manner. In addition, we confirmed that sub
      chronic administration of MPTP in mice leads to permanent neuromuscular deficits
      and depletion of dopamine and its metabolites. Our results suggest that GE is
      beneficial for the treatment of PD associated with neuromuscular disability and
      LB aggregation. 

PMID- 24103763
TI  - How a marriage with big pharma ended in divorce.

PMID- 24103765
TI  - The HTS dogma is shattered, and now there are fragments everywhere.

PMID- 24103766
TI  - In silico docking and scoring of fragments.

PMID- 24103764
TI  - Standardized cardiovascular magnetic resonance (CMR) protocols 2013 update.
AB  - This document is an update to the 2008 publication of the Society for
      Cardiovascular Magnetic Resonance (SCMR) Board of Trustees Task Force on
      Standardized Protocols. Since the time of the original publication, 3 additional
      task forces (Reporting, Post-Processing, and Congenital Heart Disease) have
      published documents that should be referred to in conjunction with the present
      document. The section on general principles and techniques has been expanded as
      more of the techniques common to CMR have been standardized. There is still a
      great deal of development in the area of tissue characterization/mapping, so
      these protocols have been in general left as optional. The authors hope that this
      document continues to standardize and simplify the patient-based approach to
      clinical CMR. It will be updated at regular intervals as the field of CMR
      advances. 

PMID- 24103767
TI  - Ligand efficiency as a guide in fragment hit selection and optimization.

PMID- 24103768
TI  - Fragments: past, present and future.

PMID- 24103769
TI  - Fragment library design: efficiently hunting drugs in chemical space.

PMID- 24103770
TI  - The heat is on: thermodynamic analysis in fragment-based drug discovery.

PMID- 24103771
TI  - Evolutionary perspective on hepatitis B virus with an expanded sampling strategy.
AB  - To investigate the role hepatitis B e antigen (HBeAg) plays in the evolution of
      hepatitis B virus (HBV), we sequenced the basic core promoter (BCP) and precore
      (preC) regions of 348 clones total from ten HBV Chinese patients. Eleven
      mutations were more frequent in HBeAg-negative patients than in HBeAg-positive
      patients. Further, the sequencing of dozens of variants was found to be necessary
      to obtain mutation profiles. Phylogenetic and median-joining network analyses
      suggested that variants from each patient had a single common ancestor
      (monophyly). Higher haplotype and nucleotide diversities were identified in HBeAg
      negative patients. Analysis of dN/dS suggested that viruses experiencing a
      stronger immune response had lower haplotype diversity. Because HBeAg
      seroconversion was associated with viral diversity it served as an indicator of
      HBV evolution. Significantly, this study indicated a larger sampling of variants
      from each patient was required to understand effectively the properties of HBV. 

PMID- 24103772
TI  - Safety and feasibility of novel technology fusing echocardiography and
      fluoroscopy images during MitraClip interventions.
AB  - AIMS: The EchoNavigator (EN) software (Philips Healthcare, Best, The Netherlands)
      enables real-time fusion of echocardiography and fluoroscopy by co-registration
      of the echocardiography probe on the x-ray image. We aimed to evaluate the
      feasibility and safety of this novel software during MitraClip procedures.
      METHODS AND RESULTS: Twenty-one patients were treated with the support of
      EchoNavigator software (EN+ patients). The primary (safety) endpoint was the
      total radiation dose. Secondary endpoints were fluoroscopy and total procedure
      time. The measurements were compared to those of 21 patients treated immediately
      before the installation of EchoNavigator (EN- patients). More MitraClips (45 vs.
      36) were implanted in the EN+ group, mirroring more complex interventions in this
      group. In EN+ patients, radiation dose (Gy/cm2) was similar compared to EN-
      patients (146.5+/-123.6 vs.146.8+/-134.1, p=0.9). Total procedure time (minutes)
      was similar in the EN+ group compared to EN- patients (136.2+/-50.2 vs. 125.7+/
      51.2, p=0.5). The main benefit of the EchoNavigator is the automated real-time
      fusion of echocardiography and fluoroscopy, leading to easier catheter
      manipulation. CONCLUSIONS: The use of EchoNavigator software was feasible and
      safe in all study patients. Further studies are necessary to confirm the benefits
      of using this software.

PMID- 24103773
TI  - Cytotoxic and genotoxic effects of water and sediment samples from gypsum mining
      area in channel catfish ovary (CCO) cells.
AB  - Man-made activities such as mining generate certain amounts of metal contaminated
      wastes which can reach aquatic environment and cause the serious effects on
      different organisms and ecosystem. Chemical analysis of the environmental samples
      is the most direct approach to reveal their pollution status but it cannot always
      provide information on biological effects to different organisms, including fish.
      This study was aimed to investigate the in vitro cytotoxicity and genotoxicity of
      water and sediment samples from gypsum mining area using the channel catfish
      ovary (CCO) cell line. Results obtained by the WST-1 assay and alkaline comet
      assay revealed that exposure of CCO cells to the same concentrations of
      contaminated water and sediment samples caused significant decrease in cell
      viability and increased DNA damages. Chemical analysis of water and sediment
      samples showed that increased concentrations of strontium, aluminum and iron were
      mainly responsible for the observed cytotoxic and genotoxic effects in CCO cells.
      The study suggested that fish CCO cells could be useful biological test-system
      for water and sediment cytotoxicity and genotoxicity assessments. 

PMID- 24103774
TI  - To adapt or not to adapt: the question of domain-general cognitive control.
AB  - What do perceptually bistable figures, sentences vulnerable to misinterpretation
      and the Stroop task have in common? Although seemingly disparate, they all
      contain elements of conflict or ambiguity. Consequently, in order to monitor a
      fluctuating percept, reinterpret sentence meaning, or say "blue" when the word
      RED is printed in blue ink, individuals must regulate attention and engage
      cognitive control. According to the Conflict Monitoring Theory (Botvinick,
      Braver, Barch, Carter, & Cohen, 2001), the detection of conflict automatically
      triggers cognitive control mechanisms, which can enhance resolution of subsequent
      conflict, namely, "conflict adaptation." If adaptation reflects the recruitment
      of domain-general processes, then conflict detection in one domain should
      facilitate conflict resolution in an entirely different domain. We report two
      novel findings: (i) significant conflict adaptation from a syntactic to a non
      syntactic domain and (ii) from a perceptual to a verbal domain, providing strong
      evidence that adaptation is mediated by domain-general cognitive control. 

PMID- 24103775
TI  - Pathophysiology of paradoxical embolism: evaluation of the role of interatrial
      septum anatomy based on the intracardiac echocardiography assessment of patients
      with right-to-left shunting.
AB  - BACKGROUND: Detailed anatomic variants of the interatrial septum in patients with
      right-to-left shunt and contribution of specific anatomies to the risk of
      ischaemic recurrences has not yet been comprehensively classified. OBJECTIVE: To
      report a classification of the anatomic variants of the interatrial septum as
      observed by intracardiac echocardiography and its correlation with clinical and
      functional characteristics. METHODS: We retrospectively reviewed the medical and
      instrumental data of 520 consecutive patients (mean age 44+/-15. 5 years, 355
      women) who had over a 10-year period undergone intracardiac echocardiography and
      right-to-left shunt catheter-based closure. The four main features used to
      analyse were: (a) diameter of the oval fossa, (b) presence and length of the
      channel, (c) presence and degree of atrial septal aneurysm, and (d) rim
      thickness. The presence of Eustachian valve was also tabulated. RESULTS: The
      combinations of interatrial septum anatomical features were classified into six
      main anatomical subgroups. Recurrent embolism, multiple ischaemic foci on brain
      magnetic resonance imaging, high grade shunt, and permanent shunt before
      transcatheter closure procedure were associated with type 2, type 4, and type 6.
      Type 4 anatomical subtype (OR 4.1, 1.5-8 [95% CI], p<0.001) and type 2+presence
      of Eustachian valve (OR 4.3, 1.6-9 [95% CI], p<0.001) were the strongest
      predictors of recurrent ischaemic events before transcatheter closure.
      CONCLUSION: Our study showed that interatrial septum anatomy greatly differs
      among patients with right-to-left shunt, as well as the risk of ischaemic
      recurrences in different anatomies.

PMID- 24103776
TI  - Cnm is a major virulence factor of invasive Streptococcus mutans and part of a
      conserved three-gene locus.
AB  - Cnm, a collagen- and laminin-binding protein present in a subset of Streptococcus
      mutans strains, mediates binding to extracellular matrices (ECM), intracellular
      invasion and virulence in the Galleria mellonella model. Antibodies raised
      against Cnm were used to confirm expression and the cell surface localization of
      Cnm in the highly invasive OMZ175 strain. Sequence analysis identified two
      additional genes (cnaB and cbpA) encoding putative surface proteins immediately
      upstream of cnm. Inactivation of cnaB and cbpA in OMZ175, individually or in
      combination, did not decrease the ability of this highly invasive and virulent
      strain to bind to different ECM proteins, invade human coronary artery
      endothelial cells (HCAEC), or kill G. mellonella. Similarly, expression of cnaB
      and cbpA in the cnm(-) strain UA159 revealed that these genes did not enhance Cnm
      related phenotypes. However, integration of cnm in the chromosome of UA159
      significantly increased its ability to bind to collagen and laminin, invade
      HCAEC, and kill G. mellonella. Moreover, the presence of antibodies against Cnm
      nearly abolished the ability of OMZ175 to bind to collagen and laminin and invade
      HCAEC, and significantly protected G. mellonella against OMZ175 infection. We
      concluded that neither CnaB nor CbpA is necessary for the expression of Cnm
      related traits. We also provided definitive evidence that Cnm is an important
      virulence factor and a suitable target for the development of novel preventive
      and therapeutic strategies to combat invasive S. mutans strains. 

PMID- 24103778
TI  - Frequency domain mediolateral balance assessment using a center of pressure
      tracking task.
AB  - Since impaired mediolateral balance can increase fall risk, especially in the
      elderly, its quantification and training might be a powerful preventive tool. We
      propose a visual tracking task (VTT) with increasing frequencies (.3-2.0Hz) and
      with center of pressure as visual feedback as an assessment method. This
      mediolateral balance assessment (MELBA) consists of two tasks, tracking a
      predictable target signal to determine physical capacity and tracking an
      unpredictable target signal to determine sensorimotor integration limitations.
      Within and between sessions learning effects and reliability in balance
      performance descriptors in both tasks were studied in 20 young adults. Balance
      performance was expressed as the phase-shift (PS) and gain (G) between the target
      and CoP in the frequency domain and cut-off frequencies at which the performance
      dropped. Results showed significant differences between the MELBA tasks in PS and
      G indicating a lower delay and higher accuracy in tracking the predictable
      target. Significant within and between sessions learning effects for the same
      measures were found only for the unpredictable task. Reliability of the cut-off
      frequencies at which PS and G performance declined and the average values within
      cut-off frequencies was fair to good (ICC .46-.66) for the unpredictable task and
      fair to excellent for the predictable task (ICC .68-.87). In conclusion, MELBA
      can reliably quantify balance performance using a predictable VTT. Additionally,
      the unpredictable tasks can give insight into the visuomotor integration
      mechanisms controlling balance and highlights MELBA's potential as a training
      tool. 

PMID- 24103777
TI  - Walking the interactome to identify human miRNA-disease associations through the
      functional link between miRNA targets and disease genes.
AB  - BACKGROUND: MicroRNAs (miRNAs) are important post-transcriptional regulators that
      have been demonstrated to play an important role in human diseases. Elucidating
      the associations between miRNAs and diseases at the systematic level will deepen
      our understanding of the molecular mechanisms of diseases. However, miRNA-disease
      associations identified by previous computational methods are far from
      completeness and more effort is needed. RESULTS: We developed a computational
      framework to identify miRNA-disease associations by performing random walk
      analysis, and focused on the functional link between miRNA targets and disease
      genes in protein-protein interaction (PPI) networks. Furthermore, a bipartite
      miRNA-disease network was constructed, from which several miRNA-disease co
      regulated modules were identified by hierarchical clustering analysis. Our
      approach achieved satisfactory performance in identifying known cancer-related
      miRNAs for nine human cancers with an area under the ROC curve (AUC) ranging from
      71.3% to 91.3%. By systematically analyzing the global properties of the miRNA
      disease network, we found that only a small number of miRNAs regulated genes
      involved in various diseases, genes associated with neurological diseases were
      preferentially regulated by miRNAs and some immunological diseases were
      associated with several specific miRNAs. We also observed that most diseases in
      the same co-regulated module tended to belong to the same disease category,
      indicating that these diseases might share similar miRNA regulatory mechanisms.
      CONCLUSIONS: In this study, we present a computational framework to identify
      miRNA-disease associations, and further construct a bipartite miRNA-disease
      network for systematically analyzing the global properties of miRNA regulation of
      disease genes. Our findings provide a broad perspective on the relationships
      between miRNAs and diseases and could potentially aid future research efforts
      concerning miRNA involvement in disease pathogenesis.

PMID- 24103779
TI  - Immediate-early gene expression in structures outside the basal ganglia is
      associated to l-DOPA-induced dyskinesia.
AB  - Long-term l-3,4-dihydroxyphenylalanine (l-DOPA) treatment in Parkinson's disease
      (PD) leads to l-DOPA-induced dyskinesia (LID), a condition thought to primarily
      involve the dopamine D1 receptor-expressing striatal medium spiny neurons.
      Activation of the D1 receptor results in increased expression of several
      molecular markers, in particular the members of the immediate-early gene (IEG)
      family, a class of genes rapidly transcribed in response to an external stimulus.
      However, several dopaminoceptive structures in the brain that are likely to be
      affected by the exogenously produced DA have received little attention although
      they might play a key role in mediating those l-DOPA-induced abnormal behaviours.
      DeltaFosB, ARC, FRA2 and Zif268 IEGs expression patterns were thus characterised,
      using unbiased stereological methods, in the whole brain of dyskinetic and non
      dyskinetic rats to identify brain nuclei displaying a transcriptional response
      specifically related to LID. Within the basal ganglia, the striatum and the
      substantia nigra pars reticulata showed an increased expression of all four IEGs
      in dyskinetic compared to non-dyskinetic rats. Outside the basal ganglia, there
      was a striking increased expression of the four IEGs in the motor cortex, the bed
      nucleus of the stria terminalis, the dorsal hippocampus, the pontine nuclei, the
      cuneiform nucleus and the pedunculopontine nuclei. Moreover, the zona incerta and
      the lateral habenula displayed an overexpression of DeltaFosB, ARC and Zif268.
      Among these structures, the IEG expression in the striatum, the bed nucleus of
      the stria terminalis, the lateral habenula, the pontine nuclei and the cuneiform
      nucleus correlate with LID severity. These results illustrate a global
      transcriptional response to a dyskinetic state in the whole brain suggesting the
      possible involvement of these structures in LID. 

PMID- 24103780
TI  - Effects of passive smoking on adult nasal respiratory mucosa.
AB  - OBJECTIVE: The present study aimed to investigate nasal mucosal changes in
      response to passive exposure to cigarette smoke. STUDY DESIGN: The study included
      20 women aged 35-51 years who were scheduled for non-rhinological surgical
      procedures, and who had at least 10 years' prolonged passive exposure to
      household cigarette smoke. During surgery, two 1-mm3 biopsies of nasal mucosa
      were taken from the lower border of the inferior turbinate. Specimens were
      processed and examined with light and transmission electron microscopy. RESULTS:
      Examination of the nasal mucosa showed several histopathological changes. The
      severity of structural changes increased with duration of smoke exposure. No
      allergic or neoplastic changes were seen. CONCLUSION: Passive exposure to
      cigarette smoke has a deleterious effect on the nasal respiratory mucosa.
      Prolonged passive smoke exposure may also induce other, significant changes not
      detected in the present study.

PMID- 24103781
TI  - Analysis of GAGE, NY-ESO-1 and SP17 cancer/testis antigen expression in early
      stage non-small cell lung carcinoma.
AB  - BACKGROUND: The unique expression pattern and immunogenic properties of
      cancer/testis antigens make them ideal targets for immunotherapy of cancer. The
      MAGE-A3 cancer/testis antigen is frequently expressed in non-small cell lung
      cancer (NSCLC) and vaccination with MAGE-A3 in patients with MAGE-A3-positive
      NSCLC has shown promising results. However, little is known about the expression
      of other cancer/testis antigens in NSCLC. In the present study the expression of
      cancer/testis antigens GAGE, NY-ESO-1 and SP17 was investigated in patients with
      completely resected, early stage, primary NSCLC. METHODS: Tumor biopsies from
      normal lung tissue and from a large cohort (n = 169) of NSCLC patients were
      examined for GAGE, NY-ESO-1 and SP17 protein expression by immunohistochemical
      analysis. The expression of these antigens was further matched to clinical and
      pathological features using univariate cox regression analysis. RESULTS: GAGE and
      NY-ESO-1 cancer/testis antigens were not expressed in normal lung tissue, while
      SP17 was expressed in ciliated lung epithelia. The frequency of GAGE, NY-ESO-1
      and SP17 expression in NSCLC tumors were 26.0% (44/169), 11.8% (20/169) and 4.7%
      (8/169), respectively, and 33.1% (56/169) of the tumors expressed at least one of
      these antigens. In general, the expression of GAGE, NY-ESO-1 and SP17 was not
      significantly associated with a specific histotype (adenocarcinoma vs. squamous
      cell carcinoma), but high-level GAGE expression (>50%) was more frequent in
      squamous cell carcinoma (p = 0.02). Furthermore, the frequency of GAGE expression
      was demonstrated to be significantly higher in stage II-IIIa than stage I NSCLC
      (17.0% vs. 35.8%; p = 0.02). Analysis of the relation between tumor expression of
      GAGE and NY-ESO-1 and survival endpoints revealed no significant associations.
      CONCLUSION: Our study demonstrates that GAGE, NY-ESO-1 and SP17 cancer/testis
      antigens are candidate targets for immunotherapy of NSCLC and further suggest
      that multi-antigen vaccines may be beneficial.

PMID- 24103782
TI  - Evaluation of reactive oxygen species scavenging activities and DNA damage
      prevention effect of Pleioblastus kongosanensis f. aureostriatus leaf extract by
      chemiluminescence assay.
AB  - Reactive oxygen species scavenging effect of Pleioblastus kongosanensis f.
      aureostriatus leaf extract against O2(-), OH and H2O2 were investigated by
      chemiluminescence methods in vitro. Bamboo grass leaves were extracted with 70%
      ethanol solution and sequentially partitioned with solvents in an order of
      increasing polarity. Among fractions of different polarity, BuOH and EtOAc
      fractions showed powerful scavenging activities than others, and showed better
      scavenging ability on OH than that of O2(-)and H2O2, with IC50 of 0.55 MUg/mL and
      0.60 MUg/mL, respectively. Both OH-induced DNA damage model by chemiluminescence
      assay and plasmid pUC18 double-strand break model by agarose gel electrophoresis
      showed that BuOH and EtOAc fractions had remarkable concentration-dependent
      prevention effect on the OH-induced damage of DNA attribute to their good
      scavenging effects on ROS. Results from the compositional analysis of different
      fractions indicate that the flavonoids in the Pleioblastus kongosanensis f.
      aureostriatus leaf may be responsible for its ROS scavenging activity and DNA
      damage prevention ability.

PMID- 24103783
TI  - Characterization of the role of EGF-A of low density lipoprotein receptor in
      PCSK9 binding.
AB  - Proprotein convertase subtilisin kexin-like 9 (PCSK9) promotes the degradation of
      low density lipoprotein receptor (LDLR) and plays an important role in regulating
      plasma LDL-cholesterol levels. We have shown that the epidermal growth factor
      precursor homology domain A (EGF-A) of the LDLR is critical for PCSK9 binding at
      the cell surface (pH 7.4). Here, we further characterized the role of EGF-A in
      binding of PCSK9 to the LDLR. We found that PCSK9 efficiently bound to the LDLR
      but not to other LDLR family members. Replacement of EGF-A in the very low
      density lipoprotein receptor (VLDLR) with EGF-A of the LDLR promoted the
      degradation of the mutant VLDLR induced by PCSK9. Furthermore, we found that
      PCSK9 bound to recombinant EGF-A in a pH-dependent manner with stronger binding
      at pH 6.0. We also identified amino acid residues in EGF-A of the LDLR important
      for PCSK9 binding. Mutations G293H, D299V, L318D, and L318H reduced PCSK9 binding
      to the LDLR at neutral pH without effect at pH 6.0, while mutations R329P and
      E332G reduced PCSK9 binding at both pH values. Thus, our findings reveal that EGF
      A of the LDLR is critical for PCSK9 binding at the cell surface (neutral pH) and
      at the acidic endosomal environment (pH 6.0), but different determinants
      contribute to efficient PCSK9 binding in different pH environments. 

PMID- 24103784
TI  - Long-term live cell microscopy studies of lipid droplet fusion dynamics in
      adipocytes.
AB  - During the adipogenic differentiation process of mesenchymal stem cells, lipid
      droplets (LDs) grow slowly by transferring lipids between each other. Recent
      findings hint at the possibility that a fusion pore is involved. In this study,
      we analyze lipid transfer data obtained in long-term label-free microscopy
      studies in the framework of a Hagen-Poiseuille model. The data obtained show a LD
      fusion process in which the lipid transfer directionality depends on the size
      difference between LDs, whereas the respective rates depend on the size
      difference and additionally on the diameter of the smaller LDs. For the data
      analysis, the viscosity of the transferred material has to be known. We
      demonstrate that a viscosity-dependent molecular rotor dye can be used to measure
      LD viscosities in live cells. On this basis, we calculate the diameter of a
      putative lipid transfer channel which appears to have a direct dependence on the
      diameter of the smaller of the two participating LDs. 

PMID- 24103785
TI  - [Molecular and therapeutic advances in Hairy cell leukemia].
AB  - Hairy cell leukemia is a rare chronic lymphoproliferative disorder. Its diagnosis
      remains difficult due to different variant forms and differential diagnosis that
      are splenic marginal zone lymphoma and b-prolymphocytic leukemia. The prognosis
      of this malignancy has been transformed by purine nucleoside analogs, interferon,
      monoclonal antibodies and recombinant immunotoxins usually used in refractory or
      relapsed disease. The discovery of BRAF V600E mutation has become the milestone
      in the disease's history since it was uniformly identified in a HCL series in
      2011. This mutation, commonly identified in melanoma, involves the protooncogene
      BRAF, a MAP3Kinase belonging to the RAF-MEK-ERK signaling pathway, which is the
      central key in several oncogenic processes. This mutation suggests disease
      specific oncogene dependence. The detection of this mutation provides an
      additional diagnosis marker (because not found in variant forms), a best for
      monitoring minimal residual disease and a therapeutic target with the BRAF
      inhibitors in specific subgroups of patients, already tested in melanoma. This
      review aims to summarize the clinical and biological aspects and treatment of
      hairy cell leukemia and discusses the perspectives provided by the discovery of
      BRAF mutation in this disease. 

PMID- 24103786
TI  - Clinical implications of cardiac hyperpolarized magnetic resonance imaging.
AB  - Alterations in cardiac metabolism are now considered a cause, rather than a
      result, of cardiac disease. Although magnetic resonance spectroscopy has allowed
      investigation of myocardial energetics, the inherently low sensitivity of the
      technique has limited its clinical application in the study of cardiac
      metabolism. The development of a novel hyperpolarization technique, based on the
      process of dynamic nuclear polarization, when combined with the metabolic tracers
      [1-(13)C] and [2-(13)C] pyruvate, has resulted in significant advances in the
      understanding of real time myocardial metabolism in the normal and diseased heart
      in vivo. This review focuses on the changes in myocardial substrate selection and
      downstream metabolism of hyperpolarized 13C labelled pyruvate that have been
      shown in diabetes, ischaemic heart disease, cardiac hypertrophy and heart failure
      in animal models of disease and how these could translate into clinical practice
      with the advent of clinical grade hyperpolarizer systems.

PMID- 24103787
TI  - Perineal burn care: French working group recommendations.
AB  - OBJECTIVES: Burns to the perineum are frequently exposed to faeces. Diverting
      colostomy is often described to prevent faecal soiling. Because this technique is
      invasive with frequent complications, use of non-surgical devices including
      specifically designed faecal management systems has been reported in perineal
      burns. METHODS: In order to standardise the faecal management strategy in
      patients with perineal burns, a group of French experts was assembled. This group
      first evaluated the ongoing practice in France by analysing a questionnaire sent
      to every French burn centre. Based on the results of this study and on literature
      data, the experts proposed recommendations on the management of perineal burns in
      adults. RESULTS: Specifically designed faecal management systems are the first
      line method to divert faeces in perineal burns. The working group proposed
      recommendations and an algorithm to assist in decisions in the management of
      perineal burns in four categories of patients, depending on total burn skin area,
      depth and extent of the perineal burn. CONCLUSION: In France, non-surgical
      devices are the leading means of faecal diversion in perineal burns. The proposed
      algorithm may assist in decisions in the management of perineal burns. The expert
      group emphasises that large clinical studies are needed to better evaluate these
      devices.

PMID- 24103788
TI  - Modelling olanzapine-induced weight gain in rats.
AB  - The second-generation antipsychotic drug olanzapine has become a widely
      prescribed drug in the treatment of schizophrenia and bipolar disorder.
      Unfortunately, its therapeutic benefits are partly outweighed by significant
      weight gain and other metabolic side effects, which increase the risk for
      diabetes and cardiovascular disease. Because olanzapine remains superior to other
      antipsychotic drugs that show less weight gain liability, insight into the
      mechanisms responsible for olanzapine-induced weight gain is crucial if it is to
      be effectively addressed. Over the past few decades, several groups have
      investigated the effects of olanzapine on energy balance using rat models.
      Unfortunately, results from different studies have not always been consistent and
      it remains to be determined which paradigms should be used in order to model
      olanzapine-induced weight gain most accurately. This review summarizes the
      effects of olanzapine on energy balance observed in different rat models and
      discusses some of the factors that appear to contribute to the inconsistencies in
      observed effects. In addition it compares the effects reported in rats with
      clinical findings to determine the predictive validity of different paradigms. 

PMID- 24103789
TI  - The role of EPH receptors in cancer-related epithelial-mesenchymal transition.
AB  - Erythropoietin-producing hepatoma (EPH) receptors are considered the largest
      family of receptor tyrosine kinases and play key roles in physiological and
      pathologic processes in development and disease. EPH receptors are often
      overexpressed in human malignancies and are associated with poor prognosis.
      However, the functions of EPH receptors in epithelial-mesenchymal transition
      (EMT) remain largely unknown. This review depicts the relationship between EPH
      receptors and the EMT marker E-cadherin as well as the crosstalk between EPH
      receptors and the signaling pathways involved EMT. Further discussion is focused
      on the clinical significance of EPH receptors as candidates for targeting in
      cancer therapeutics. Finally, we summarize how targeted inhibition of both EPH
      receptors and EMT-related signaling pathways represents a novel strategy for
      cancer treatment. 

PMID- 24103790
TI  - Recent advances regarding the role of ABC subfamily C member 10 (ABCC10) in the
      efflux of antitumor drugs.
AB  - ABCC10, also known as multidrug-resistant protein 7 (MRP7), is the tenth member
      of the C subfamily of the ATP-binding cassette (ABC) superfamily. ABCC10 mediates
      multidrug resistance (MDR) in cancer cells by preventing the intracellular
      accumulation of certain antitumor drugs. The ABCC10 transporter is a 171-kDa
      protein that is localized on the basolateral cell membrane. ABCC10 is a broad
      specificity transporter of xenobiotics, including antitumor drugs, such as
      taxanes, epothilone B, vinca alkaloids, and cytarabine, as well as modulators of
      the estrogen pathway, such as tamoxifen. In recent years, ABCC10 inhibitors,
      including cepharanthine, lapatinib, erlotinib, nilotinib, imatinib, sildenafil,
      and vardenafil, have been reported to overcome ABCC10-mediated MDR. This review
      discusses some recent and clinically relevant aspects of the ABCC10 drug efflux
      transporter from the perspective of current chemotherapy, particularly its
      inhibition by tyrosine kinase inhibitors and phosphodiesterase type 5 inhibitors.

PMID- 24103792
TI  - The cost-effectiveness of supervised exercise for the treatment of intermittent
      claudication.
AB  - BACKGROUND: Supervised exercise (SE) is thought to result in improvements in
      walking distance and quality of life compared with unsupervised exercise (USE) in
      people with intermittent claudication. However, the cost-effectiveness of SE is
      unclear. As a result, many patients are currently unable to access supervised
      programmes. METHODS: We searched MEDLINE, Embase, Cochrane, and Cinahl databases
      to identify randomised controlled trials comparing USE with SE in adults with
      intermittent claudication. A Markov model was developed to estimate costs and
      quality adjusted life years (QALYs) from an NHS and personal social services
      perspective. Quality of life was obtained from the included clinical trials.
      Resource use was modelled on current programmes and unit costs were based on
      published sources. RESULTS: Depending on estimated rates of compliance, SE was
      cost-effective in over 75% of model simulations, with an incremental cost
      effectiveness ratio of L711 to L1,608 per QALY gained. The model was sensitive to
      long-term effects of exercise on cardiovascular risk and quality of life.
      CONCLUSIONS: SE is more cost-effective than USE for the treatment of people with
      intermittent claudication. Supervised programmes should be made widely available
      and offered as a first line treatment to people with intermittent claudication.

PMID- 24103791
TI  - A prospective analysis of factors that influence weight loss in patients
      undergoing radiotherapy.
AB  - Malnutrition occurs frequently in patients with cancer. Indeed, a variety of
      nutritional and tumor-related factors must be taken into account in these
      patients. Recognizing this relationship, we aimed to prospectively evaluate the
      risk factors that influence weight loss in patients undergoing radiotherapy with
      oral nutritional supplementation and dietetic counseling. Weight loss of 74
      patients during radiotherapy and 1 month after treatment was analyzed. Parameters
      such as age, gender, tumor location, tumor stage, Eastern Cooperative Oncology
      Group performance status (ECOG PS) score, and the use of chemotherapy were
      analyzed to evaluate their influence on weight loss. All patients underwent oral
      nutritional supplementation and dietetic counseling. Forty-six (65.7%) patients
      lost weight, with a mean weight loss of (4.73 +/- 3.91) kg, during radiotherapy.
      At 1 month after treatment, 45 (66.2%) patients lost weight, presenting a mean
      weight loss of (4.96 +/- 4.04) kg, corresponding to a (6.84 +/- 5.24)% net
      reduction from their baseline weight. Head and neck cancer patients had a mean
      weight loss of (3.25 +/- 5.30) kg, whereas the remaining patients had a mean
      weight loss of (0.64 +/- 2.39) kg (P = 0.028) during radiotherapy. In the
      multivariate analysis, the head and neck tumor location (P = 0.005), use of
      chemotherapy (P = 0.011), and ECOG PS score of 2-3 (P = 0.026) were considered
      independent risk factors. Nutritional status and parameters, such as tumor
      location (especially the head and neck), the use of chemotherapy, and the ECOG PS
      score, should be evaluated before radiotherapy because these factors can
      influence weight loss during radiotherapy and 1 month after treatment. 

PMID- 24103793
TI  - Corynebacterium endocarditis of a percutaneously placed transcatheter pulmonary
      valve.
AB  - We report a case of endocarditis of a transcatheter pulmonary valve-in-valve in a
      14-year-old boy with tetralogy of Fallot. He presented with recurrent low-grade
      fevers, lethargy, and anorexia. Multiple blood cultures grew a gram-positive rod,
      Corynebacterium pseudodiphtheriticum. He was taken to the operating room for
      removal of the vegetative endocarditis and pulmonary valve replacement. 

PMID- 24103794
TI  - Carotid dissection mimicking a new attack of cluster headache.
AB  - BACKGROUND: Symptomatic cluster headache (CH) secondary to internal carotid
      artery dissection (ICAD) has been frequently reported, however, as far as we
      know, the coexistence of episodic CH and acute symptomatic CH secondary to ICAD
      has not. CASE REPORT: A 39 year-old man, affected by episodic CH since the age of
      19, presented an atypical headache associated with his usual autonomic symptoms.
      After a series of negative tests, MRA eventually revealed dissection of the right
      distal internal carotid artery. DISCUSSION AND CONCLUSIONS: The coexistence of
      episodic CH and acute CH symptomatic of ICAD in our patient suggests that, at
      least in some cases, CH and ICAD may be different expressions of a common
      underlying cause: hidden vessel wall damage. When risk factors and the change -
      though partial - of clinical features suggest symptomatic cases, CH patients have
      to be strictly monitored over time. Given the lack of a gold standard
      investigation for dynamic diseases such as dissections, these patients require
      multimodal diagnostic investigation over time, even in cases where exams are
      normal at onset.

PMID- 24103795
TI  - 3D pharmacophore elucidation and virtual screening.

PMID- 24103796
TI  - 3D pharmacophores as tools for activity profiling.

PMID- 24103797
TI  - Grid-derived structure-based 3D pharmacophores and their performance compared to
      docking.

PMID- 24103798
TI  - Strategies for 3D pharmacophore-based virtual screening.

PMID- 24103799
TI  - 'Fuzziness' in pharmacophore-based virtual screening and de novo design.

PMID- 24103800
TI  - Conformations and 3D pharmacophore searching.

PMID- 24103801
TI  - History of 3D pharmacophore searching: commercial, academic and open-source
      tools.

PMID- 24103802
TI  - The scaffold hopping potential of pharmacophores.

PMID- 24103804
TI  - Thiamine deficiency leads to reduced nitric oxide production and vascular
      dysfunction in rats.
AB  - BACKGROUND AND AIMS: Thiamine deficiency is a condition that is known to cause
      damage to the nervous and cardiovascular systems because it interferes with
      cellular metabolism. It is well known that the control of vascular function is
      highly dependent on the production of nitric oxide (NO) by NO synthases. Studies
      exploring the physiological relevance of NO signaling under conditions of
      thiamine deficiency are scarce. The present study sought to investigate whether
      chronic metabolic changes would cause alterations in vascular responsiveness.
      METHODS AND RESULTS: By removing thiamine from the diet, we observed a reduced
      acetylcholine-mediated relaxation and an increased phenylephrine-mediated
      vasoconstriction in the aortas containing functional endothelium. Removal of the
      endothelium or the pre-treatment of vessels with l-NAME restored the contractile
      responses to the level of controls. Conversely, indomethacin did not modify
      phenylephrine-mediated contractions. We also used carbon microsensors to
      continually measure NO production in situ while simultaneously measuring the
      vascular tone. The results revealed a significant decrease in NO production.
      Western blot analysis showed a decreased expression of the total eNOS in the
      thiamine-deficient aorta compared to the control. Concentration-response curves
      for phenylephrine indicated no difference between the control and deficient
      groups in the presence and absence of SOD or Tyron. The NO donor DEA-NONOate
      produced a concentration-dependent relaxation response in the endothelium-denuded
      vessels that did not differ between the control and thiamine-deficient rats.
      CONCLUSION: Thiamine deficiency modulates eNOS-dependent NO production, leading
      to a decreased vasorelaxation and an increased contractile response in the rat
      aorta.

PMID- 24103805
TI  - Biphasic positive airway pressure minimizes biological impact on lung tissue in
      mild acute lung injury independent of etiology.
AB  - INTRODUCTION: Biphasic positive airway pressure (BIVENT) is a partial support
      mode that employs pressure-controlled, time-cycled ventilation set at two levels
      of continuous positive airway pressure with unrestricted spontaneous breathing.
      BIVENT can modulate inspiratory effort by modifying the frequency of controlled
      breaths. Nevertheless, the optimal amount of inspiratory effort to improve
      respiratory function while minimizing ventilator-associated lung injury during
      partial ventilatory assistance has not been determined. Furthermore, it is
      unclear whether the effects of partial ventilatory support depend on acute lung
      injury (ALI) etiology. This study aimed to investigate the impact of spontaneous
      and time-cycled control breaths during BIVENT on the lung and diaphragm in
      experimental pulmonary (p) and extrapulmonary (exp) ALI. METHODS: This was a
      prospective, randomized, controlled experimental study of 60 adult male Wistar
      rats. Mild ALI was induced by Escherichia coli lipopolysaccharide either
      intratracheally (ALI(p)) or intraperitoneally (ALI(exp)). After 24 hours, animals
      were anesthetized and further randomized as follows: (1) pressure-controlled
      ventilation (PCV) with tidal volume (V(t)) = 6 ml/kg, respiratory rate = 100
      breaths/min, PEEP = 5 cmH2O, and inspiratory-to-expiratory ratio (I:E) = 1:2; or
      (2) BIVENT with three spontaneous and time-cycled control breath modes (100, 75,
      and 50 breaths/min). BIVENT was set with two levels of CPAP (P(high) = 10 cmH2O
      and P(low) = 5 cmH2O). Inspiratory time was kept constant (T(high) = 0.3 s).
      RESULTS: BIVENT was associated with reduced markers of inflammation, apoptosis,
      fibrogenesis, and epithelial and endothelial cell damage in lung tissue in both
      ALI models when compared to PCV. The inspiratory effort during spontaneous
      breaths increased during BIVENT-50 in both ALI models. In ALI(p), alveolar
      collapse was higher in BIVENT-100 than PCV, but decreased during BIVENT-50, and
      diaphragmatic injury was lower during BIVENT-50 compared to PCV and BIVENT-100.
      In ALI(exp), alveolar collapse during BIVENT-100 and BIVENT-75 was comparable to
      PCV, while decreasing with BIVENT-50, and diaphragmatic injury increased during
      BIVENT-50. CONCLUSIONS: In mild ALI, BIVENT had a lower biological impact on lung
      tissue compared to PCV. In contrast, the response of atelectasis and
      diaphragmatic injury to BIVENT differed according to the rate of
      spontaneous/controlled breaths and ALI etiology.

PMID- 24103803
TI  - The SH2B1 obesity locus and abnormal glucose homeostasis: lack of evidence for
      association from a meta-analysis in individuals of European ancestry.
AB  - BACKGROUND/AIMS: The development of type 2 diabetes (T2D) is influenced both by
      environmental and by genetic determinants. Obesity is an important risk factor
      for T2D, mostly mediated by obesity-related insulin resistance. Obesity and
      insulin resistance are also modulated by the genetic milieu; thus, genes
      affecting risk of obesity and insulin resistance might also modulate risk of T2D.
      Recently, 32 loci have been associated with body mass index (BMI) by genome-wide
      studies, including one locus on chromosome 16p11 containing the SH2B1 gene.
      Animal studies have suggested that SH2B1 is a physiological enhancer of the
      insulin receptor and humans with rare deletions or mutations at SH2B1 are obese
      with a disproportionately high insulin resistance. Thus, the role of SH2B1 in
      both obesity and insulin resistance makes it a strong candidate for T2D. However,
      published data on the role of SH2B1 variability on the risk for T2D are
      conflicting, ranging from no effect at all to a robust association. METHODS: The
      SH2B1 tag SNP rs4788102 (SNP, single nucleotide polymorphism) was genotyped in
      6978 individuals from six studies for abnormal glucose homeostasis (AGH),
      including impaired fasting glucose, impaired glucose tolerance or T2D, from the
      GENetics of Type 2 Diabetes in Italy and the United States (GENIUS T2D)
      consortium. Data from these studies were then meta-analyzed, in a Bayesian
      fashion, with those from DIAGRAM+ (n = 47,117) and four other published studies
      (n = 39,448). RESULTS: Variability at the SH2B1 obesity locus was not associated
      with AGH either in the GENIUS consortium (overall odds ratio (OR) = 0.96; 0.89
      1.04) or in the meta-analysis (OR = 1.01; 0.98-1.05). CONCLUSION: Our data
      exclude a role for the SH2B1 obesity locus in the modulation of AGH.

PMID- 24103806
TI  - Cross-sectional study: Does combining optical coherence tomography measurements
      using the 'Random Forest' decision tree classifier improve the prediction of the
      presence of perimetric deterioration in glaucoma suspects?
AB  - OBJECTIVES: To develop a classifier to predict the presence of visual field (VF)
      deterioration in glaucoma suspects based on optical coherence tomography (OCT)
      measurements using the machine learning method known as the 'Random Forest'
      algorithm. DESIGN: Case-control study. PARTICIPANTS: 293 eyes of 179 participants
      with open angle glaucoma (OAG) or suspected OAG. INTERVENTIONS: Spectral domain
      OCT (Topcon 3D OCT-2000) and perimetry (Humphrey Field Analyser, 24-2 or 30-2
      SITA standard) measurements were conducted in all of the participants. VF damage
      (Ocular Hypertension Treatment Study criteria (2002)) was used as a 'gold
      standard' to classify glaucomatous eyes. The 'Random Forest' method was then used
      to analyse the relationship between the presence/absence of glaucomatous VF
      damage and the following variables: age, gender, right or left eye, axial length
      plus 237 different OCT measurements. MAIN OUTCOME MEASURES: The area under the
      receiver operating characteristic curve (AROC) was then derived using the
      probability of glaucoma as suggested by the proportion of votes in the Random
      Forest classifier. For comparison, five AROCs were derived based on: (1) macular
      retinal nerve fibre layer (m-RNFL) alone; (2) circumpapillary (cp-RNFL) alone;
      (3) ganglion cell layer and inner plexiform layer (GCL+IPL) alone; (4) rim area
      alone and (5) a decision tree method using the same variables as the Random
      Forest algorithm. RESULTS: The AROC from the combined Random Forest classifier
      (0.90) was significantly larger than the AROCs based on individual measurements
      of m-RNFL (0.86), cp-RNFL (0.77), GCL+IPL (0.80), rim area (0.78) and the
      decision tree method (0.75; p<0.05). CONCLUSIONS: Evaluating OCT measurements
      using the Random Forest method provides an accurate prediction of the presence of
      perimetric deterioration in glaucoma suspects.

PMID- 24103807
TI  - Bordetella pertussis: why is it still circulating?
AB  - Bordetella pertussis is the causal agent of whooping cough, a highly contagious
      respiratory disease that is life-threatening in infants under the age of three
      months and may also be very severe in pregnant women and seniors. This disease
      can be prevented by vaccination but it remains a public health problem in many
      developed and developing countries.(1) So, why is B. pertussis still circulating?
      We need to consider several aspects of this vaccine-preventable disease when
      answering this question: (i) the history of the disease and the historical
      context in which the vaccine was developed; (ii) the type of vaccine used; (iii)
      the vaccination strategy and coverage; (iv) the disease surveillance after the
      introduction of generalized vaccination and (v) the surveillance for the causal
      agent of the disease. 

PMID- 24103808
TI  - Full evaporation headspace gas chromatography for sensitive determination of high
      boiling point volatile organic compounds in low boiling matrices.
AB  - Determination of volatile organic components (VOC's) is often done by static
      headspace gas chromatography as this technique is very robust and combines easy
      sample preparation with good selectivity and low detection limits. This technique
      is used nowadays in different applications which have in common that they have a
      dirty matrix which would be problematic in direct injection approaches. Headspace
      by nature favors the most volatile compounds, avoiding the less volatile to reach
      the injector and column. As a consequence, determination of a high boiling
      solvent in a lower boiling matrix becomes challenging. Determination of VOCs
      like: xylenes, cumene, N,N-dimethylformamide (DMF), dimethyl sulfoxide (DMSO),
      N,N-dimethylacetamide (DMA), N-methyl-2-pyrrolidone (NMP), 1,3-dimethyl-2
      imidazolidinone (DMI), benzyl alcohol (BA) and anisole in water or water soluble
      products are an interesting example of the arising problems. In this work, a
      headspace variant called full evaporation technique is worked out and validated
      for the mentioned solvents. Detection limits below 0.1 MUg/vial are reached with
      RSD values below 10%. Mean recovery values ranged from 92.5 to 110%. The
      optimized method was applied to determine residual DMSO in a water based cell
      culture and DMSO and DMA in tetracycline hydrochloride (a water soluble sample).

PMID- 24103809
TI  - Impact of plasmid size on the purification of model plasmid DNA vaccines by
      phenyl membrane adsorbers.
AB  - Plasmid DNA (pDNA) offers a versatile platform for the development of new
      pharmaceuticals. This versatility also adds in variability among plasmid products
      most of the times sharing only the same basic molecular structure. Membrane
      chromatography experiments performed with a Sartorius((r)) Phenyl 3 mL spiral
      cartridge and differently sized plasmids (3.70 kbp, 6.05 kbp and 10.4 kbp) show
      that the strength of interaction of pDNA isoforms with HIC membrane adsorbers
      depends on size. These differences in relative binding strength were explored
      using a stepwise elution strategy of decreasing buffer conductivities in order to
      increase the purity of supercoiled (SC) pDNA isoforms. The open circular (OC)
      isoforms of all plasmids eluted earlier at a similar conductivity of 190 mS/cm,
      independently of the hydrodynamic diameter (Dh). A drop in conductivity of 16.0
      mS/cm, 23 mS/cm and 19 mS/cm had to be imposed to elute the supercoiled (SC)
      counterparts of the 3.70 kbp, 6.05 kbp and 10.4 kbp, respectively. This
      corresponds to relative binding strengths of the SC over OC isoforms of 1.09,
      1.14 and 1.11. Unlike the OC isoforms, the behavior of SC isoforms was dependent
      of the Dh. The purified and pooled plasmid fractions were assayed and
      demonstrated high degree of purity, compliant with regulatory agencies criteria:
      over 99% RNA removal, endotoxin levels below 0.001 EU/MUg pDNA and undetectable
      protein content by BCA assay.

PMID- 24103810
TI  - Analytical solutions and moment analysis of chromatographic models for
      rectangular pulse injections.
AB  - This work focuses on the analysis of two standard liquid chromatographic models,
      namely the lumped kinetic model and the equilibrium dispersive model. Analytical
      solutions, obtained by means of Laplace transformation, are derived for
      rectangular single solute concentration pulses of finite length and breakthrough
      curves injected under linear conditions. In order to analyze the solute transport
      behavior by means of the two models, the temporal moments up to fourth order are
      calculated from the Laplace-transformed solutions. The limiting cases of
      continuous injection and negligible mass transfer limitations are evaluated. For
      validation, the analytical solutions are compared with the numerical solutions of
      models using the discontinuous Galerkin finite element method. Results of
      different case studies are discussed for linear and nonlinear adsorption
      isotherms. The discontinuous Galerkin method is employed to obtain moments for
      both linear and nonlinear models numerically. Analytically and numerically
      determined concentration profiles and moments were found to be in good agreement.

PMID- 24103812
TI  - High-dose glucocorticoid aggravates TBI-associated corticosteroid insufficiency
      by inducing hypothalamic neuronal apoptosis.
AB  - Emerging experimental and clinical data suggest that severe illness, such as
      traumatic brain injury (TBI), can induce critical illness-related corticosteroid
      insufficiency (CIRCI). However, underlying mechanisms of this TBI-associated
      CIRCI remain poorly understood. We hypothesized that dexamethasone (DXM), a
      synthetic glucocorticoid, which was widely used to treat TBI, induces
      hypothalamic neuronal apoptosis to aggravate CIRCI. To test this hypothesis, we
      have evaluated the dose effect of DXM (1 or 10mg/kg) on the development of acute
      CIRCI in rats with fluid percussion injury-induced TBI and on cultured rat
      hypothalamic neurons in vitro (DXM, 10(-5)-10(-8)mol/L). Corticosterone Increase
      Index was recorded as the marker for CIRCI. In addition, MTT and TUNEL assays
      were used to measure the viability and apoptosis of hypothalamic neurons in
      primary culture. Moreover, high-resolution hopping probe ion conductance
      microscopy (HPICM) was used to monitor the DXM-induced morphological changes in
      neurons. The incidence of acute CIRCI was significantly higher in the high-dose
      DXM group on post-injury day 7. Cellular viability was significantly decreased
      from 12h to 24h after the treatment with a high-dose of DXM. A significantly
      increase in TUNEL positive cells were detected in cultured cells treated with a
      high-dose of DXM after 18h. Neurites of hypothalamic neuron were dramatically
      thinner and the numbers of dendritic beadings increased in neurons treated with
      the high dose of DXM for 12h. In conclusion, high-dose DXM induced hypothalamic
      neurons to undergo apoptosis in vivo and in vitro, which may aggravate TBI
      associated CIRCI. 

PMID- 24103811
TI  - Magnesium modulates parathyroid hormone secretion and upregulates parathyroid
      receptor expression at moderately low calcium concentration.
AB  - BACKGROUND: The interest on magnesium (Mg) has grown since clinical studies have
      shown the efficacy of Mg-containing phosphate binders. However, some concern has
      arisen for the potential effect of increased serum Mg on parathyroid hormone
      (PTH) secretion. Our objective was to evaluate the direct effect of Mg in the
      regulation of the parathyroid function; specifically, PTH secretion and the
      expression of parathyroid cell receptors: CaR, the vitamin D receptor (VDR) and
      FGFR1/Klotho. METHODS: The work was performed in vitro by incubating intact rat
      parathyroid glands in different calcium (Ca) and Mg concentrations. RESULTS:
      Increasing Mg concentrations from 0.5 to 2 mM produced a left shift of PTH-Ca
      curves. With Mg 5 mM, the secretory response was practically abolished. Mg was
      able to reduce PTH only if parathyroid glands were exposed to moderately low Ca
      concentrations; with normal-high Ca concentrations, the effect of Mg on PTH
      inhibition was minor or absent. After 6-h incubation at a Ca concentration of 1.0
      mM, the expression of parathyroid CaR, VDR, FGFR1 and Klotho (at mRNA and protein
      levels) was increased with a Mg concentration of 2.0 when compared with 0.5 mM.
      CONCLUSIONS: Mg reduces PTH secretion mainly when a moderate low calcium
      concentration is present; Mg also modulates parathyroid glands function through
      upregulation of the key cellular receptors CaR, VDR and FGF23/Klotho system.

PMID- 24103813
TI  - Hyaluronic acid-coated chitosan nanoparticles: molecular weight-dependent effects
      on morphology and hyaluronic acid presentation.
AB  - Chitosan nanoparticles are popular carriers for the delivery of macromolecular
      payloads, e.g. nucleic acids. In this study, nanoparticles were prepared via
      complexation with triphosphate (TPP) anions and were successively coated with
      hyaluronic acid (HA). Key variables of the preparative process (e.g. chitosan and
      HA molecular weight) were optimised in view of the maximisation of loading with
      DNA, of the Zeta potential and of the dimensional stability, and the resulting
      particles showed excellent storage stability. We have focused on the influence of
      chitosan molecular weight on nanoparticle properties. Larger molecular weight
      increased their porosity (=decreased cross-link density), and this caused also
      larger dimensional changes in response to variations in osmotic pressure or upon
      drying. The dependency of nanoparticle porosity on chitosan molecular weight had
      a profound effect on the adsorption of HA on the nanoparticles; HA was apparently
      able to penetrate deeply into the more porous high molecular weight (684 kDa)
      chitosan nanoparticles, while it formed a corona around those composed of more
      densely cross-linked low molecular weight (25 kDa) chitosan. Atomic Force
      Microscopy (AFM) allowed not only to highlight the presence of this corona, but
      also to estimate its apparent thickness to about 20-30 nm (in a dry state). The
      different morphology has a significant effect on the way HA is presented to
      biomolecules, and this has specific relevance in relation to interactions with HA
      receptors (e.g. CD44) that influence kinetics and mechanism of nanoparticle
      uptake. Finally, it is worth to mention that chitosan molecular weight did not
      appear to greatly affect the efficiency of nanoparticle loading with DNA, but
      significantly influenced its chitosanase-triggered release, with high molecular
      chitosan nanoparticles seemingly more prone to degradation by this enzyme.

PMID- 24103814
TI  - Hypoxic resistance of hypodermically transplanted pancreatic islets by using cell
      absorbable antioxidant Tat-metallothionein.
AB  - Subcutaneous site is ideal for clinical islet transplantation because it has the
      advantage of simple operation procedure under local anesthesia and can be
      biopsied when needed. However, the transplantation outcomes at subcutaneous site
      have been disappointing due to hypoxia-induced oxidative stress by poor
      vascularization. We hypothesized that subcutaneously transplanted islets would
      have hypoxia resistance by using internalization of metallothionein (MT), an
      antioxidant scavenging enzyme, which was mediated by fusion between MT and cell
      penetrating Tat peptide. The Tat-MT was dose-dependently transduced into islets
      without any damage. Tat-MT-treated islets could be protected from oxidative
      stress induced by intracellular nitric oxide donor, sodium nitroprusside (SNP).
      When Tat-MT-treated islets were subcutaneously transplanted into diabetic nude
      mice, they normally controlled the blood glucose levels without severe
      fluctuation (median survival time (MST): >30 days), whereas most untreated islets
      were rejected (MST 17 days). From the intraperitoneal glucose tolerance test 5
      days after posttransplantation, glucose responsiveness of Tat-MT-treated islets
      was similar to that of normal healthy mice, while untreated islets had delayed
      glucose responsiveness. From the results of immunohistochemical stain, Tat-MT
      treated islets had strong anti-insulin positive cells and lower anti-HIF-1alpha
      positive cells. However, untreated islets had rare anti-insulin positive cells
      and strong anti-HIF-1alpha-positive cells. Collectively, these findings
      demonstrated that Tat-MT delivery into islet could offer a new strategy for
      successful islet transplantation under subcutaneous space.

PMID- 24103815
TI  - Molecular docking simulation studies on potent butyrylcholinesterase inhibitors
      obtained from microbial transformation of dihydrotestosterone.
AB  - BACKGROUND: Biotransformation is an effective technique for the synthesis of
      libraries of bioactive compounds. Current study on microbial transformation of
      dihydrotestosterone (DHT) (1) was carried out to produce various functionalized
      metabolites. RESULTS: Microbial transformation of DHT (1) by using two fungal
      cultures resulted in potent butyrylcholinesterase (BChE) inhibitors.
      Biotransformation with Macrophomina phaseolina led to the formation of two known
      products, 5alpha-androstan-3beta,17beta-diol (2), and 5beta-androstan
      3alpha,17beta-diol (3), while biotransformation with Gibberella fujikuroi yielded
      six known metabolites, 11alpha,17beta-dihydroxyandrost-4-en-3-one (4), androst
      1,4-dien-3,17-dione (5), 11alpha-hydroxyandrost-4-en-3,17-dione (6), 11alpha
      hydroxyandrost-1,4-dien-3,17-dione (7), 12beta-hydroxyandrost-1,4-dien-3,17-dione
      (8), and 16alpha-hydroxyandrost-1,4-dien-3,17-dione (9). Metabolites 2 and 3 were
      found to be inactive, while metabolite 4 only weakly inhibited the enzyme.
      Metabolites 5-7 were identified as significant inhibitors of BChE. Furthermore,
      predicted results from docking simulation studies were in complete agreement with
      experimental data. Theoretical results were found to be helpful in explaining the
      possible mode of action of these newly discovered potent BChE inhibitors.
      Compounds 8 and 9 were not evaluated for enzyme inhibition activity both in vitro
      and in silico, due to lack of sufficient quantities. CONCLUSION:
      Biotransformation of DHT (1) with two fungal cultures produced eight known
      metabolites. Metabolites 5-7 effectively inhibited the BChE activity.
      Cholinesterase inhibition is among the key strategies in the management of
      Alzheimer's disease (AD). The experimental findings were further validated by in
      silico inhibition studies and possible modes of action were deduced.

PMID- 24103816
TI  - Alteration of consciousness in focal epilepsy: the global workspace alteration
      theory.
AB  - Alteration of consciousness (AOC) is an important clinical manifestation of
      partial seizures that greatly impacts the quality of life of patients with
      epilepsy. Several theories have been proposed in the last fifty years. An
      emerging concept in neurology is the global workspace (GW) theory that postulates
      that access to consciousness (from several sensorial modalities) requires
      transient coordinated activity from associative cortices, in particular the
      prefrontal cortex and the posterior parietal associative cortex. Several lines of
      evidence support the view that partial seizures alter consciousness through
      disturbance of the GW. In particular, a nonlinear relation has been shown between
      excess of synchronization in the GW regions and the degree of AOC. Changes in
      thalamocortical synchrony occurring during the spreading of the ictal activity
      seem particularly involved in the mechanism of altered consciousness. This link
      between abnormal synchrony and AOC offers new perspectives in the treatment of
      the AOC since means of decreasing consciousness alteration in seizures could
      improve patients' quality of life.

PMID- 24103817
TI  - Certain secondary antiepileptic drugs can rescue hippocampal injury following a
      critical growth period despite poor anticonvulsant activity and cognitive
      deficits.
AB  - Clinical and experimental studies have shown that many common secondary
      antiepileptic drugs (AEDs) are ineffective at blocking seizures in adulthood;
      however, some afford neuroprotection. In early development, certain AEDs cause
      apoptosis; however, it is unknown whether these drugs are neurotoxic to the
      juvenile brain following a developmentally regulated proapoptotic period and
      whether they alter the seizure threshold, seizure-induced neuronal vulnerability,
      and/or cognitive function. Lamotrigine (LTG), carbamazepine (CBZ), phenytoin
      (PHT), valproate (VPA), and topiramate (TPM) were systemically administered to
      rat pups for 7days beginning on postnatal (P) day 14 (P14), then half the animals
      were injected with kainate (KA) to trigger seizures, an age when the CA1
      subregion becomes preferentially sensitive to status epilepticus. Histological
      outcome, seizure severity, and learning and memory were determined with an
      electroencephalograph (EEG), silver impregnation, and a water-maze swim task.
      None of the AEDs tested significantly attenuated behavioral or electrographic
      seizures. Phenytoin increased mortality, identifying a detrimental side effect of
      this drug. The other drugs (LTG, VPA, TPM, and CBZ) afforded different amounts of
      protection to the CA1 subregion but not to the CA3 subregion or extrahippocampal
      structures. With the exception of VPA, AED-treated animals lagged behind during
      swim task acquisition. All groups improved in the water-maze swim task over time,
      particularly on the last trials; however, the average escape latency was still
      impaired for TPM-treated animals and all AED+KA-treated groups. Thus, while
      certain AEDs demonstrated some neuroprotective effects, poor antiepileptic
      activity, memory impairment, and other deleterious side effects were observed
      with these drugs suggesting that the search for potentially more effective and
      tolerated agents is essential for improving clinical outcome in children and
      adolescents with epilepsy. 

PMID- 24103818
TI  - [Vitamin D and breast cancer: physiopathology, biological and clinical
      implications].
AB  - There is a recent increase in interest of vitamin D and breast cancer, facing the
      number of publications on the subject. This increase have several reasons, on the
      one hand, vitamin D deficiency is more and more prevalent and, on the other hand,
      there are new data that highlights the extra-bone effects of vitamin D,
      especially in breast cancer, the vitamin D is involved in the breast cancer risk
      factor, the prognosis, and the interaction with breast cancer treatments. This
      combination between vitamin D deficiency and breast cancer is extremely usual,
      and combined with all cancer clinical parameters: the incidence, the tumour
      biology, the clinical presentation, the prognosis, and the antineoplastic
      treatment tolerance. This vitamin D deficiency is increased after adjuvant cancer
      treatments. And yet, this problem increases bone metabolism disruptions in breast
      cancer patients, inducing osteoporotic risk at long time, even though this
      population is curable. This problem is therefore serious in the adjuvant breast
      cancer treatment. Unfortunately, in this population, the current recommendations
      are clearly insufficient, and the current randomized clinical trial results would
      contribute to define the best way to correct the vitamin D deficiency, quickly
      and secure.

PMID- 24103819
TI  - Anatomic assessment of femoral tunnel by transtibial drilling technique in double
      bundle anterior cruciate ligament reconstruction: an in vivo study.
AB  - OBJECTIVE: To evaluate the anatomy of femoral tunnels created by simulated
      transtibial technique in double-bundle anterior cruciate ligament (ACL)
      reconstruction. METHODS: Two tibial tunnels, anteromedial (AM) and posterolateral
      (PL), were drilled 45?and 55?to tibial plateau respectively. On the femoral side,
      the AM and PL tunnels were drilled through anteriomedial portal. After the four
      tunnels were established, the shaft of a reamer was introduced into the joint
      through tibial tunnel and reached against the lateral wall of intercondylar
      notch. The position that the reamer shaft can reach was marked and recorded.
      RESULTS: Neither femoral AM nor PL tunnel opening can be fully or partially
      reached by the reamer shaft through the tibial AM tunnel in all cases. The
      evaluation through the tibial PL tunnel showed that only in 8 of 50 cases (16%)
      the femoral AM tunnel opening and in 4 cases (8%) the PL opening can be fully
      reached. On the other hand, in 12 cases (24%) the femoral AM tunnel opening and
      in 10 cases (20%) the PL opening can be partially reached by the shafts through
      the tibial PL tunnel. CONCLUSION: The result strongly suggests that transtibial
      technique is not well competent for femoral tunnel drilling in anatomic double
      bundle ACL reconstruction as we have hypothesized.

PMID- 24103820
TI  - Local effect of celecoxib on peripheral nerve repair combined with silicone
      tubulization in rat.
AB  - OBJECTIVE: To assess local effect of celecoxib on nerve regeneration in a rat
      sciatic nerve transection model. METHODS: Forty-five male healthy white Wistar
      rats were randomly divided into three experimental groups (n equal to 15 for
      each): sham-operation (SHAM), control (SIL) and celecoxib treated (SIL/CLX)
      groups. In SHAM group after anesthesia left sciatic nerve was exposed and after
      homeostasis muscle was sutured. In SIL group the left sciatic nerve was exposed
      in the same way and transected proximal to tibioperoneal bifurcation leaving a 10
      mm gap. Proximal and distal stumps were each inserted into a silicone tube and
      filled with 10 microlitre phosphate buffered solution. In SIL/CLX group defect
      was bridged using a silicone tube filled with 10 microlitre celecoxib (0.1 g/L).
      RESULTS: Functional study and gastrocnemius muscle mass confirmed faster and
      better recovery of regenerated axons in SIL/CLX than in SIL group (P less than
      0.05). Morphometric indices of regenerated fibers showed number and diameter of
      the myelinated fibers in SIL/CLX were significantly greater than those in control
      group. In immunohistochemistry, location of reactions to S-100 in SIL/CLX was
      clearly more positive than that in SIL group. CONCLUSION: Response to local
      treatment of celecoxib demonstrates that it influences and improves functional
      recovery of peripheral nerve regeneration.

PMID- 24103821
TI  - A two-choice strategy through a medial tibial approach for the treatment of pilon
      fractures with posterior or anterior fragmentation.
AB  - OBJECTIVE: The anterolateral approach to the tibia has been popularized for the
      management of tibial pilon fractures. For complex fracture patterns a combined
      anterolateral/anteromedial approach is suitable but a high rate of complication
      has been reported. In our retrospective study a two-choice strategy adopting a
      medial tibial approach was proposed for the treatment of pilon fractures with
      anterior or posterior fragmentation. METHODS: Based on an anatomic study of
      tibial pilon fractures, we retrospectively analyzed the fractures with primary
      posterior, posterior-lateral or anterior, anterior-lateral (Tillaux-Chaput)
      involvement of the distal tibia. This retrospective study consisted of 18
      patients with a closed tibial plafond fracture. The inclusion criteria were: (1)
      pre- sence of an anterior/anterolateral type fragment or a posterior (Volkmann)
      type fragment involving larger than 25% of the articular surface, (2) a minimum
      follow-up of 12 months, (3) a fibula fracture associated with a medial column
      fracture of the distal tibia, and (4) soft tissue conditions at the time of
      operation that did not compromise the choice of surgical access (Tscherne
      classification for closed fractures: grade 0 and grade 1). Tibial plafond
      fractures were classified into two groups: one presenting anterior and the other
      with posterior rim (Volkmann) fragments. RESULTS: Most patients achieved a good
      clinical recovery in terms of range of motion and Olerud-Molander scale scores.
      Only three patients presented a grade 2 osteoarthritis at the 12 month follow-up.
      CONCLUSION: Our two-choice strategy highlights concepts which have been
      previously debated and described in the literature. But a new extended protocol
      for surgical approach to the distal tibia, including more fracture patterns and
      their association should be further investigated.

PMID- 24103822
TI  - Effect of osteoprotegerin in combination with interleukin-6 on inhibition of
      osteoclast differentiation.
AB  - OBJECTIVE: To observe the effect of recombinant interleukin-6 (IL-6) and
      osteoprotegerin (OPG) on inhibiting bone absorption induced by receptor activator
      for nuclear factor-kB ligand (RANKL) in murine osteoclast precursor cells (OCPs)
      model. METHODS: RAW 264.7 cells were solely treated with 50 ng/ml RANKL for 1
      day, and then they were divided into three groups: RANKL (control group),
      RANKL+IL-6 (IL-6 group) and RANKL+IL-6+OPG (combination group). These cells were
      harvested and investigated by means of HE staining under light microscope after
      consecutive 9 days. Furthermore, staining tartrate-resistant acid
      phosphatase(TRAP)-positive multinucleated cells were detected by inverted phase
      contrast microscope. The absorption pits of bone slices were observed under
      scanning electron microscope. RESULTS: The number of mature osteoclast cells in
      control group was more than that in IL-6 alone or IL-6 combined with OPG group (P
      less than 0.05). Interestingly, this experiment has also demonstrated that there
      was a large number of TRAP-positive multinucleated osteoclasts (more than 3
      nuclei) and several bone absorption formation in the control group, whereas the
      outcome was completely different in both IL-6 group and IL-6+OPG group (P less
      than 0.05). CONCLUSION: IL-6 can suppress the differentiation of mature
      osteoclasts as directly adding it into the RAW 264.7 cells induced by 50 ng/ml
      RANKL, and further the effect of osteolysis is remarkably reduced. When treatment
      with IL-6 combined with OPG, a more effective strategy for the treatment of
      osteoporosis is reached.

PMID- 24103823
TI  - Educational level and age as contributing factors to road traffic accidents.
AB  - OBJECTIVE: This research analyzes data on road traffic accidents (RTA) in Fars
      province, whose roads are among the highly dangerous ones in Iran. It
      investigates educational level and age involved in RTA in order to discover
      patterns that can prevent or decrease accidents. METHODS: This research made use
      of data visualization techniques to find hidden patterns. The data included
      mortality rate related to RTA in Fars province and were obtained from Fars
      Forensic Medicine Registry covering a period of 1 year from March 21, 2010 to
      March 21, 2011. All data were analyzed using SPSS 11.5. The results were reported
      as descriptive indices such as frequency (percentage). The Chi-square test was
      applied to the data concerning educational level and age. P value less than 0.05
      was considered significant. RESULTS: In the mentioned period, 1 831 people were
      killed, out of whom un/lowly educated people (69.6%) accounted for the highest
      mortality rate. The significant relationship between educational level and
      mortality rate was found (X2 equal to 275.98, P less than 0.0001).Also three was
      a significant association between age and mortality rate (X2 equal to 371.20, P
      less than 0.0001). Young people (age between 20 and 29 years) contribute to
      higher RTA mortality rate compared with other age groups. CONCLUSION: The
      educational level and age are significantly correlated to mortality rate. The
      youth and un/lowly educated people suffer more fatal RTA.

PMID- 24103824
TI  - Brachiocephalic trunk and left brachiocephalic vein injuries following
      penetrating right sternoclavicular junction trauma: a case report.
AB  - A 46-year-old male sustained severe pe- netrating injury by a sharp instrument to
      his right upper sternoclavicular junction. The wound tract was from suprasternal
      notch to mediastinum. Exploratory operation via median sternotomy under general
      anesthesia found a large mediastinal septum hematoncus, as well as
      brachiocephalic trunk and left brachiocephalic vein injuries. The perforating
      vascular wounds were repaired with 5-0 prolene suture. He was recovered
      uneventfully and discharged 9 days after operation. There was no sequel found
      during 7 years follow-up. 

PMID- 24103825
TI  - Tubercular arthritis of the elbow joint following olecranon fracture fixation and
      the role of TGF-beta in its pathogenesis.
AB  - Tuberculosis (TB) occurring after a closed bone fracture in the patient with no
      history of TB and no evidence of TB infection at the time of initial fracture is
      a rare entity. We report one such case of a 48-year-old female, who presented in
      the emergency department with an olecranon fracture which was open reduced and
      internally fixed with tension band wiring. Patient presented in the outpatient
      department with serosanguineous discharge at 3 weeks after surgery. The discharge
      was sent for culture and sensitivity tests, and the patient was managed by
      antibiotics and daily dressings. There was wound dehiscence and the underlying
      implant was exposed, which was removed at 12 weeks after surgery. Repeat
      debridements and dressings continued for 6 months, but the discharge from the
      wound site continued. X-rays of the elbow performed at 6 months raised the
      suspicion of TB, which was confirmed by Ziel-Neelsen staining and
      histopathological examination of the debrided tissue. Following the confirmation,
      patient was put on antitubercular drugs. The patient responded to antitubercular
      drug therapy (ATT), the purulent discharge from the wound ceased, and eventually
      the wound healed after 2 months of starting ATT. 

PMID- 24103826
TI  - Kirschner wire migration from the right second rib to the right ventricle: a case
      report.
AB  - Migrations of orthopedic wires to cardiovascular system are uncommon and rarely
      reported. We report a case of right ventricle embolization with the Kirschner
      wire that was used for right 2nd rib osteosynthesis 2 years and 8 months
      previously in a 50-year-old man. The patient was asymptomatic and migration of
      the Kirschner wire was discovered by routine chest X-ray. An 8 cm-long Kirschner
      wire was successfully retrieved from the right ventricle. The treatment strategy
      for Kirschner wire removal from right ventricle is discussed. 

PMID- 24103827
TI  - Double floating arm injury in a child: a case report and review of the
      literature.
AB  - The combination of ipsilateral humeral fractures at three different levels namely
      proximal, shaft and supracondyle has been rarely defined in the literature. We
      present a case report on such a complex injury in a 10-year-old child after
      falling down from the second floor of his house while playing. To the best of our
      knowledge, no such case report exists in the English literature. We define it as
      double floating arm injury. Firstly, shaft of humerus was open reduced and fixed
      with 4.5 mm narrow dynamic compression plate. Then closed reduction and pinning
      of the supracondylar humerus under an image intensifier was obtained. Open
      reduction using deltopectoral approach to the proximal humerus was done and the
      fracture was fixed with three K-wires. Ipsilateral multiple fractures in children
      often result from high energy trauma. Immediate reduction and fixation is
      required. Usually surgeons need to treat simple fractures firstly, which makes
      the subsequent treatment of complex fractures easier. 

PMID- 24103828
TI  - Complete palmer lunate enucleation---is proximal row carpectomy or wrist
      arthrodesis the only choice?
AB  - Perilunate dislocations are rare injuries of the wrist and complete dislocation
      of the lunate is also rare. There is controversy in literature regarding the
      optimal management of such injuries. Complete lunate enucleation is associated
      with high rate of osteonecrosis of lunate thus wrist arthrodesis or proximal row
      carpectomy has been advocated as primary treatment for such injuries. We report a
      case of transradial styloid complete palmar lunate enucleation in a 25-year-old
      male patient who sustained injury to the left wrist due to fall on outstretched
      hand. Carpal row salvage surgery initially by closed reduction and wrist
      distractor application followed by open reduction and internal fixation with K
      wires along with ligamentous repair resulted in restoration of normal wrist
      anatomy and good functional outcome. As many of these injuries are missed on
      initial presentation and outcome is poor for missed injuries, prompt diagnosis
      and early surgical management to restore vascularity of lunate is recommended. 

PMID- 24103829
TI  - Acute femoral artery pseudoaneurysm due to lesser trochanter fragment: an unusual
      complication of an intertrochanteric fracture.
AB  - False aneurysm of the femoral artery is a rare complication of intertrochanteric
      fracture. Most of these situations are due to iatrogenic trauma or the trauma
      itself and are rarely caused by dislocated bone fragments. Here we report a case
      of a 72-year-old man who presented acutely with a pseudoaneurysm of the
      superficial femoral artery from the spike of a lesser trochanter fragment.
      Percutaneous endovascular treatment of the pseudoaneurysm with a covered stent
      was undertaken on an urgent basis. Five days later, the patient was operated upon
      and the lesser trochanter fragment was excised through an anterior incision and
      the intertrochanteric fracture was fixed using dynamic hip screws. The fracture
      was united at 10 weeks. At one-year's follow-up, there were no graft-related
      complications. This case illustrates that an intertrochanteric fracture with a
      displaced lesser trochanter fragment can present acutely with bleeding and a
      pseudoaneurysm of the femoral artery. 

PMID- 24103830
TI  - Femoral head fracture without hip dislocation.
AB  - Femoral head fractures without dislocation or subluxation are extremely rare
      injuries. We report a neglected case of isolated comminuted fracture of femoral
      head without hip dislocation or subluxation of one year duration in a 36-year-old
      patient who sustained a high energy trauma due to road traffic accident. He
      presented with painful right hip and inability to bear full weight on right lower
      limb with Harris hip score of 39. He received cementless total hip replacement.
      At latest follow-up of 2.3 years, functional outcome was excellent with Harris
      hip score of 95. Such isolated injuries have been described only once in the
      literature and have not been classified till now. The purpose of this report is
      to highlight the extreme rarity, possible mechanism involved and a novel
      classification system to classify such injuries. 

PMID- 24103831
TI  - Compartment syndrome of thigh and lower leg with disruption of the popliteal
      vascular bundle after being run over by a 25-ton truck.
AB  - Compartment syndrome of the thigh is a rare condition, potentially resulting in
      devastating functional outcome. Increasing intracompartmental pressure which
      suppresses microcirculation and capillary perfusion may lead to cellular anoxia
      and muscle ischemia. The muscle compartments in the thigh have a more compliant
      fascia and blend anatomically into the open compartments of the pelvis, thus
      compensating higher volumes than the compartments in the lower leg. We present a
      previously unreported case in which the limb of a 36-year-old man was run over by
      a 25-ton truck. He presented with a sensomotor deficit in his left lower leg with
      full paralysis of the shank muscles and absence of all foot pulses. CT scan
      showed a huge haematoma in the thigh with active bleeding out of the popliteal
      artery into the haematoma which has already expanded into the muscle compartments
      of the lower leg. The limb had a disastrous compartment syndrome of the thigh and
      lower leg with disruption of the popliteal neurovascular bundle; however, no
      bones in the limb were fractured. A complete fasciotomy of all the lower limb
      muscle compartments was immediately performed. The artery was reconstructed with
      interposition of the smaller saphenous vein, which was already interrupted
      through the initial trauma. 

PMID- 24103832
TI  - Simplified pancreatoduodenectomy for complex blunt pancreaticoduodenal injury.
AB  - A 34-year-old man admitted to our department with complex blunt
      pancreaticoduodenal injury after a car accident. The wall of the first, second,
      and third portions of the duodenum was extensively lacerated, and the pancreas
      was longitudinally transected along the superior mesenteric vein-portal vein
      trunk. The pancreatic head and the uncinate process were devitalized and the
      distal common bile duct and the proximal main pancreatic duct were completely
      detached from the Vater ampulla. The length of the stump of distal common bile
      located at the cut surface of remnant pancreas was approximately 0.6 cm. A
      simplified Kausch-Whipple's procedure was performed after debridement of the
      devitalized pancreatic head and resection of the damaged duodenum in which the
      stump of distal common bile duct and the pancreatic remnant were embedded into
      the jejunal loop. Postoperative wound abscess appeared that eventually recovered
      by conservative treatment. During 16 months follow-up the patient has been stable
      and healthy. A simplified pancreaticoduodenectomy is a safe alternative for the
      Whipple procedure in managing complex pancreaticoduodenal injury in a
      hemodynamically stable patient. 

PMID- 24103833
TI  - Periprosthetic subtrochanteric femoral fracture in a megaprosthesis of the knee.
AB  - We report a rare case of periprosthetic posttraumatic fracture of subtrochanteric
      region of femur after a megaprosthesis of the knee, done for resistant nonunion
      of distal femur with secondary osteoarthrosis in a 51 years old man. Treatment
      with a locking femoral plate was able to achieve primary union with a good
      result. 

PMID- 24103834
TI  - Designing trauma registry system using a logical framework approach.
AB  - While trauma registries provide the mechanisms to collect comprehensive, timely
      and accurate data related to the injuries and evaluate trauma care systems, they
      have not been established in most developing countries. On the other hand, in
      complex projects that have large aims, a logical framework approach (LFA) can
      help summarize and describe the multiple branches of the project systematically,
      and elucidate the main goals, extensive objectives, activities and expected
      outcomes. Therefore a LFA can be used to design and guide trauma registry project
      management, to integrate the cultural, clinical and capacity variations among
      countries; and to ensure early alignment of the project's design and evaluation. 

PMID- 24103836
TI  - Innovative methods in drug regulatory sciences.

PMID- 24103837
TI  - Is quantitative benefit-risk modelling of drugs desirable or possible?

PMID- 24103835
TI  - Hypoxia and HIFs in regulating the development of the hematopoietic system.
AB  - Many physiologic processes during the early stages of mammalian ontogeny,
      particularly placental and vascular development, take place in the low oxygen
      environment of the uterus. Organogenesis is affected by hypoxia inducible factor
      (HIF) transcription factors that are sensors of hypoxia. In response to hypoxia,
      HIFs activate downstream target genes - growth and metabolism factors. During
      hematopoietic system ontogeny, blood cells and hematopoietic progenitor/stem
      cells are respectively generated from mesodermal precursors, hemangioblasts, and
      from a specialized subset of endothelial cells that are hemogenic. Since HIFs are
      known to play a central role in vascular development, and hematopoietic system
      development occurs in parallel to that of the vascular system, several studies
      have examined the role of HIFs in hematopoietic development. The response to
      hypoxia has been examined in early and mid-gestation mouse embryos through
      genetic deletion of HIF subunits. We review here the data showing that
      hematopoietic tissues of the embryo are hypoxic and express HIFs and HIF
      downstream targets, and that HIFs regulate the development and function of
      hematopoietic progenitor/stem cells. 

PMID- 24103838
TI  - Patient opinions and preferences in drug development and regulatory decision
      making.

PMID- 24103839
TI  - New approaches to strengthen pharmacovigilance.

PMID- 24103840
TI  - On the edge of new technologies (advanced therapies, nanomedicines).

PMID- 24103842
TI  - Post-innovation innovation of medicinal products.

PMID- 24103841
TI  - Weighing benefit-risk of medicines: concepts and approaches.

PMID- 24103843
TI  - Metabolic syndrome and major depression.
AB  - Major depression is associated with a 4-fold increased risk for premature death,
      largely accounted by cardiovascular disease (CVD). The relationship between
      depression and CVD is thought to be mediated by the so-called metabolic syndrome
      (MeS). Epidemiological studies have consistently demonstrated a co-occurrence of
      depression with MeS components, ie, visceral obesity, dyslipidemia, insulin
      resistance, and hypertension. Although the exact mechanisms linking MeS to
      depression are unclear, different hypotheses have been put forward. On the one
      hand, MeS could be the hallmark of the unhealthy lifestyle habits of depressed
      patients. On the other, MeS and depression might share common alterations of the
      stress system, including the hypothalamus-pituitary-adrenal (HPA) axis, the
      autonomic nervous system, the immune system, and platelet and endothelial
      function. Both the conditions induce a low grade chronic inflammatory state that,
      in turn, leads to increased oxidative and nitrosative (O&NS) damage of neurons,
      pancreatic cells, and endothelium. Recently, neurobiological research revealed
      that peripheral hormones, such as leptin and ghrelin, which are classically
      involved in homeostatic energy balance, may play a role in mood regulation.
      Metabolic risk should be routinely assessed in depressed patients and taken into
      account in therapeutic decisions. Alternative targets should be considered for
      innovative antidepressant agents, including cytokines and their receptors,
      intracellular inflammatory mediators, glucocorticoids receptors, O&NS pathways,
      and peripheral mediators. 

PMID- 24103844
TI  - Propulsion of swimming microrobots inspired by metachronal waves in ciliates:
      from biology to material specifications.
AB  - The quest for swimming microrobots originates from possible applications in
      medicine, especially involving navigation in bodily fluids. Swimming
      microorganisms have become a source of inspiration because their propulsion
      mechanisms are effective in the low-Reynolds number regime. In this study, we
      address a propulsion mechanism inspired by metachronal waves, i.e. the
      spontaneous coordination of cilia leading to the fast swimming of ciliates. We
      analyse the biological mechanism (referring to its particular embodiment in
      Paramecium caudatum), and we investigate the contribution of its main features to
      the swimming performance, through a three-dimensional finite-elements model, in
      order to develop a simplified, yet effective artificial design. We propose a
      bioinspired propulsion mechanism for a swimming microrobot based on a continuous
      cylindrical electroactive surface exhibiting perpendicular wave deformations
      travelling longitudinally along its main axis. The simplified propulsion
      mechanism is conceived specifically for microrobots that embed a micro-actuation
      system capable of executing the bioinspired propulsion (self-propelled
      microrobots). Among the available electroactive polymers, we select polypyrrole
      as the possible actuation material and we assess it for this particular
      embodiment. The results are used to appoint target performance specifications for
      the development of improved or new electroactive materials to attain metachronal
      waves-like propulsion. 

PMID- 24103845
TI  - A review of vitamin D status and CVD.
AB  - Beyond the well-accepted effects on the skeleton, low vitamin D status has been
      linked to increased risk of several non-skeletal disease, including CVD. If low
      serum 25-hydroxyvitamin D (25(OH)D) concentration is causally linked to risk of
      CVD then this is important not only because low vitamin D status is quite common
      particularly in winter in countries above 40 degrees N, but also of key relevance
      is the fact that such low vitamin D status can be improved by food-based
      strategies. The overarching aim of the present paper is to review the current
      evidence-base to support a link between low vitamin D status and CVD risk. The
      review initially briefly overviews how mechanistically vitamin D may play a role
      in CVD and then reviews the current available evidence-base to support a link
      between low vitamin D status and CVD risk, with particular emphasis on data from
      the randomised control trials, cohort studies and recent meta-analysis data as
      well as to the conclusions of a number of authoritative agencies/bodies. Finally,
      the review summarises current serum 25(OH)D concentrations within a select number
      of adult populations in the context of different definitions of vitamin D status
      proposed recently, and then briefly highlights food-based strategies for
      increasing vitamin D intake and status. In conclusion, at present the data for a
      causal link between low vitamin D status and CVD are mixed and ambiguous;
      however, should causality be affirmed by ongoing and future studies, there are
      food-based strategies for enhanced vitamin D status in the population which could
      ultimately lower risk of CVD. 

PMID- 24103847
TI  - Activation of signaling pathways downstream of the brain-derived neurotrophic
      factor receptor, TrkB, in the rat brain by vagal nerve stimulation and
      antidepressant drugs.
AB  - Vagal nerve stimulation (VNS) has been approved for treatment resistant
      depression (TRD) by the Food and Drug Administration (FDA) since 2005. However,
      the cellular and molecular targets responsible for its effects are still not
      characterized. Previously, chronic administration of VNS to rats was found to
      phosphorylate tyrosine 515 on TrkB, the neurotrophin receptor, whereas
      traditional antidepressants did not do this. In the present study, Western blot
      analysis was used to characterize activation due to phosphorylation in the
      hippocampus of down-stream pathways linked to specific key tyrosine residues on
      TrkB (namely Y816 and Y515) after either acute or chronic administration of VNS
      and traditional antidepressant drugs. Chronic administration of VNS caused
      phosphorylation of effectors linked to Y 515; namely Akt, ERK and p70S6 kinase,
      but this was not produced by either desipramine or sertraline. All the
      treatments, when given chronically, caused phosphorylation of the transcription
      factor, CREB. Acute administration of all the treatments also caused
      phosphorylation of PLCgamma1 but this was not maintained with chronic treatment.
      Further research is required to determine what role, if any, activation of down
      stream targets of Y515 plays in the behavioural effects of VNS. 

PMID- 24103846
TI  - Role of IGF-1 pathway in lung fibroblast activation.
AB  - BACKGROUND: IGF-1 is elevated in pulmonary fibrosis and acute lung injury, where
      fibroblast activation is a prominent feature. We previously demonstrated that
      blockade of IGF pathway in murine model of lung fibrosis improved outcome and
      decreased fibrosis. We now expand that study to examine effects of IGF pathway on
      lung fibroblast behaviors that could contribute to fibrosis. METHODS: We first
      examined mice that express alphaSMA promoter upstream of GFP reporter treated
      with A12, a blocking antibody to IGF-1 receptor, after bleomycin induced lung
      injury. We then examined the effect of IGF-1 alone, or in combination with the
      pro-fibrotic cytokine TGFbeta on expression of markers of myofibroblast
      activation in vitro, including alphaSMA, collagen alpha1, type 1, collagen
      alpha1, type III, and TGFbeta expression. RESULTS: After bleomycin injury, we
      found decreased number of alphaSMA-GFP + cells in A12 treated mice, validated by
      alphaSMA immunofluorescent staining. We found that IGF-1, alone or in combination
      with TGF-beta, did not affect alphaSMA RNA expression, promoter activity, or
      protein levels when fibroblasts were cultured on stiff substrate. IGF-1
      stimulated Col1a1 and Col3a1 expression on stiff substrate. In contrast, IGF-1
      treatment on soft substrate resulted in upregulation of alphaSMA gene and protein
      expression, as well as Col1a1 and Col3a1 transcripts. In conclusion, IGF-1
      stimulates differentiation of fibroblasts into a myofibroblast phenotype in a
      soft matrix environment and has a modest effect on alphaSMA stress fiber
      organization in mouse lung fibroblasts.

PMID- 24103848
TI  - CDKN2B expression in adipose tissue of familial combined hyperlipidemia patients.
AB  - The purpose of this study was to determine the core biological processes
      perturbed in the subcutaneous adipose tissue of familial combined hyperlipidemia
      (FCHL) patients. Annotation of FCHL and control microarray datasets revealed a
      distinctive FCHL transcriptome, characterized by gene expression changes
      regulating five overlapping systems: the cytoskeleton, cell adhesion and
      extracellular matrix; vesicular trafficking; lipid homeostasis; and cell cycle
      and apoptosis. Expression values for the cell-cycle inhibitor CDKN2B were
      increased, replicating data from an independent FCHL cohort. In 3T3-L1 cells,
      CDKN2B knockdown induced C/EBPalpha expression and lipid accumulation. The minor
      allele at SNP site rs1063192 (C) was predicted to create a perfect seed for the
      human miRNA-323b-5p. A miR-323b-5p mimic significantly reduced endogenous CDKN2B
      protein levels and the activity of a CDKN2B 3'UTR luciferase reporter carrying
      the rs1063192 C allele. Although the allele displayed suggestive evidence of
      association with reduced CDKN2B mRNA in the MuTHER adipose tissue dataset, family
      studies suggest the association between increased CDKN2B expression and FCHL
      lipid abnormalities is driven by factors external to this gene locus. In
      conclusion, from a comparative annotation analysis of two separate FCHL adipose
      tissue transcriptomes and a subsequent focus on CDKN2B, we propose that
      dysfunctional adipogenesis forms an integral part of FCHL pathogenesis. 

PMID- 24103850
TI  - Reconstructing spatially extended brain sources via enforcing multiple transform
      sparseness.
AB  - Accurate estimation of location and extent of neuronal sources from EEG/MEG
      remain challenging. In the present study, a new source imaging method, i.e.
      variation and wavelet based sparse source imaging (VW-SSI), is proposed to better
      estimate cortical source locations and extents. VW-SSI utilizes the L1-norm
      regularization method with the enforcement of transform sparseness in both
      variation and wavelet domains. The performance of the proposed method is assessed
      by both simulated and experimental MEG data, obtained from a language task and a
      motor task. Compared to L2-norm regularizations, VW-SSI demonstrates
      significantly improved capability in reconstructing multiple extended cortical
      sources with less spatial blurredness and less localization error. With the use
      of transform sparseness, VW-SSI overcomes the over-focused problem in classic SSI
      methods. With the use of two transformations, VW-SSI further indicates
      significantly better performance in estimating MEG source locations and extents
      than other SSI methods with single transformations. The present experimental
      results indicate that VW-SSI can successfully estimate neural sources (and their
      spatial coverage) located in close areas while responsible for different
      functions, i.e. temporal cortical sources for auditory and language processing,
      and sources on the pre-bank and post-bank of the central sulcus. Meantime, all
      other methods investigated in the present study fail to recover these phenomena.
      Precise estimation of cortical source locations and extents from EEG/MEG is of
      significance for applications in neuroscience and neurology. 

PMID- 24103851
TI  - Investigating age-related differences in responses to screening items for
      internalising disorders in three national surveys.
AB  - BACKGROUND: Epidemiological studies typically report lower prevalence of mental
      disorders among older adults relative to middle-aged and young adults. A possible
      explanation is that age-related bias in the screening items of diagnostic
      instruments leads to older adults being differentially screened out of the full
      assessment. This study investigated potential age-related bias in screening items
      for internalising disorders in three epidemiological surveys. METHOD: Measurement
      invariance was estimated for the internalising disorder screening items in the
      2007 and 1997 Australian National Survey of Mental Health and Wellbeing, and the
      2001-2002 National Epidemiologic Survey on Alcohol and Related Conditions. These
      surveys assessed mental disorders using the Composite International Diagnostic
      Interview (CIDI) and the Alcohol Use Disorder and Associated Disabilities
      Interview Schedule-DSM-IV Version (AUDADIS-IV). A series of multi-group
      confirmatory factor analyses (CFA) were performed for each survey across older
      (65-85 years), middle (35-64 years) and young (16-34 years) adults. RESULTS:
      Differences between successive CFA models for each survey were negligible,
      indicating measurement invariance across age groups for the CIDI and AUDADIS-IV
      screening items. LIMITATIONS: The number of items and symptoms representing
      internalising pathology differed between surveys. The samples excluded people in
      aged-care institutions. CONCLUSIONS: While findings do not rule out that other
      measurement errors may be present (e.g., age-related bias in the remaining
      items), these results support the validity of the screening items in the CIDI and
      AUDADIS-IV. Low prevalence estimates of internalising disorders in older adults
      are unlikely attributable to differences in response patterns to screening items.

PMID- 24103849
TI  - Fusing DTI and fMRI data: a survey of methods and applications.
AB  - The relationship between brain structure and function has been one of the centers
      of research in neuroimaging for decades. In recent years, diffusion tensor
      imaging (DTI) and functional magnetic resonance imaging (fMRI) techniques have
      been widely available and popular in cognitive and clinical neurosciences for
      examining the brain's white matter (WM) micro-structures and gray matter (GM)
      functions, respectively. Given the intrinsic integration of WM/GM and the
      complementary information embedded in DTI/fMRI data, it is natural and well
      justified to combine these two neuroimaging modalities together to investigate
      brain structure and function and their relationships simultaneously. In the past
      decade, there have been remarkable achievements of DTI/fMRI fusion methods and
      applications in neuroimaging and human brain mapping community. This survey paper
      aims to review recent advancements on methodologies and applications in
      incorporating multimodal DTI and fMRI data, and offer our perspectives on future
      research directions. We envision that effective fusion of DTI/fMRI techniques
      will play increasingly important roles in neuroimaging and brain sciences in the
      years to come. 

PMID- 24103852
TI  - Prevalence of minor depression in elderly persons with and without mild cognitive
      impairment: a systematic review.
AB  - BACKGROUND: Minor depression (MinD) and mild cognitive impairment (MCI) are
      common disorders in late life that often coexist. The aim of the present review
      is to demonstrate prevalence rates of minor depression in older patients with and
      without MCI. METHODS: Electronic database searches were performed through
      Medline, ISI Web of Knowledge, Psycinfo, and Cochrane library. Two independent
      reviewers extracted the original studies based on inclusion criteria:
      representative study population aged 55 and older, diagnostics of MinD according
      to DSM. Data on prevalence rates, risk factors, comorbidity and health care usage
      were analyzed. RESULTS: Point prevalence for MinD is higher in medical settings
      (median 14.4%) than in the community-based settings (median 10.4%) and primary
      care patients (median 7.7%). Although minor depression is rarely investigated in
      elderly persons with MCI, nearly 20% of patients with MCI seem to suffer from
      MinD. No data was found on the prevalence of MCI in patients with MinD. Risk
      factors associated with MinD include female gender, history of cerebrovascular
      diseases, generalized anxiety disorder, loneliness, and long-term institutional
      care. LIMITATIONS: Methodological differences of included studies resulted in a
      broad range of prevalence rates. No data is shown regarding the prevalence of MCI
      in MinD group due to insufficient evidence. CONCLUSIONS: Our review indicates
      that MinD is frequent in elderly population. MCI among those subjects has not
      been sufficiently investigated. Future studies based on clinical structured
      interviews should be performed in longitudinal design in order to differentiate
      late-life depression from progressive MCI or early manifestation of Alzheimer's
      disease.

PMID- 24103853
TI  - Neurocognitive changes in depressed patients in psychodynamic psychotherapy,
      therapy with fluoxetine and combination therapy.
AB  - BACKGROUND: Randomized controlled trials (RCTs) examining the efficacy of
      different forms of therapy for depression are relatively common. However, there
      are not many RCTs comparing neurocognitive effects of these treatments.
      Neurocognitive changes across three types of treatment for depression were
      compared. Long-term psychodynamic psychotherapy (LTPP) was compared with
      fluoxetine treatment, and their combination, in the treatment of moderate
      depression. METHODS: A 272 adult patients with beck depression inventory (BDI)
      scores 20-35 were randomized to receive LTPP, fluoxetine monotherapy or their
      combination for a 24 months period. The Wechsler adult intelligence scale version
      III (WAIS-III) was the primary neuropsychological measure. RESULT: Multilevel
      mixed model analyses indicated that there were neurocognitive changes within and
      between treatments, with statistically significant differences over time (p>.01).
      LTPP and combined treatment seemed to be more efficacious in modifying specific
      areas of cognition than fluoxetine alone. LIMITATIONS: Sample very homogenous,
      threatening external validity. CONCLUSIONS: LTPP and its combination with
      fluoxetine demonstrated to be effective for specific neurocognitive increasing in
      patients with moderate depression. This study suggests marked differences over
      time in the neurocognitive effects between the three treatment forms compared.
      Results found here may be of clinical relevance for building bridges between
      pharmacotherapy and psychodynamic psychotherapy.

PMID- 24103854
TI  - Depression, anxiety and loss of resilience after multiple traumas: an
      illustration of a mediated moderation model of sensitization in a group of
      children who survived the Nazi Holocaust.
AB  - BACKGROUND: Depressive and anxiety disorders (DAD) have become a major public
      health problem. Multiple trauma is known to increase the risk of DAD through a
      sensitization mechanism. We investigate the hypothesis that resilience is a
      mediator of this mechanism. METHODS: Former Hidden Children (FHC), the Jewish
      youths who spent World War II in various hideaway shelters across Nazi-occupied
      Europe, were compared with a control group. In each group, we measured the
      presence of multiple traumas, the resilience with the Resilience Scale for
      Adults, which has a six factors solution, and the DAD with the Hopkins Symptoms
      Checklist. We test a mediated moderation model with childhood trauma as the
      predictor; Later trauma as the moderator; Resilience as the mediator; and DAD as
      the outcome variable. RESULTS: Results are consistent with a sensitization model
      of DAD mediated by resilience: confrontation with a primary trauma during
      childhood followed by secondary trauma(s) after childhood damages resilience,
      which, in turn, results in higher level of DAD. LIMITATIONS: We are unable to
      differentiate if the sensitization process is a consequence of the nature of the
      trauma endured by FHC (long-standing exposure to extreme external events) or a
      consequence of the fact that this first trauma occurred during childhood.
      CONCLUSIONS: Resilience construct is multi-factorial and a limited damaging of
      some of the factors is sufficient to lead to DAD even if other factors remain
      unaltered. Resilience can be altered by multiple traumas and, therefore, needs to
      be bolstered in therapy sessions.

PMID- 24103855
TI  - Editorial (for "The billboard").

PMID- 24103858
TI  - Go East.

PMID- 24103856
TI  - Calreticulin transacetylase mediated upregulation of thioredoxin by 7,8-diacetoxy
      4-methylcoumarin enhances the antioxidant potential and the expression of
      vascular endothelial growth factor in peripheral blood mononuclear cells.
AB  - Extensive research carried out in our group on polyphenolic acetates (PAs)
      substantiated the potential role of PAs in causing diverse biological and
      pharmacological actions. Our earlier investigations firmly established the
      calreticulin transacetylase (CRTAase) catalyzed activation of nitric oxide
      synthase (NOS) by PAs. In this report, we have studied the effect of 7,8
      diacetoxy-4-methylcoumarin (DAMC, a model PA) and other acetoxy coumarins on the
      thioredoxin and VEGF expression in human peripheral blood mononuclear cells
      (PBMCs), with a view to substantiate our earlier observation that DAMC was a
      superb inducer of angiogenesis. Real time RT-PCR analysis revealed the enhanced
      expression of thioredoxin reductase (TRXR) and diminished expression of
      thioredoxin interacting protein (TRXIP) leading to the increased expression and
      activity of thioredoxin (TRX) in PBMCs due to the the action of DAMC. The fact
      that TRX activity of PBMCs was enhanced by various acetoxy coumarins in tune with
      their affinity to CRTAase as substrate, suggested the possible activation of TRX
      due to acetylation. The overexpression of thioredoxin was found to correlate with
      that of VEGF as proved by real time RT-PCR and VEGF -ELISA results, apart from
      the DAMC-caused enhanced production of NO acting as an inducer of VEGF. Moreover,
      the intracellular ROS levels were also found to be reduced drastically, by DAMC
      thus reducing the oxidative stress in cells. These observations strongly
      evidenced the crucial role of TRX in DAMC-induced tissue angiogenesis with the
      involvement of VEGF. 

PMID- 24103859
TI  - [Is the surgeon still the main prognosis factor?].
AB  - Assessment of surgeon's influence on the results of cancer surgery is complex.
      Investigation field is extremely large and should differentiate surgeon's impact
      from the one of surgery. This can result in major differences in the rate of
      postoperative complications and deaths, in the indication and use of technically
      difficult surgeries, and also in long-term results. The surgeon's impact is
      correlated with his activity volume for each type of major procedures and is
      independent from hospital activity volume. It persists independently of major
      progresses in hospital organization and process standardization. Data from the
      literature confirm the prognosis importance of the surgeon in cancer outcome. In
      the future, the timely implementation of established, evidence-based guidelines
      and checklists programs could prevent large number of deaths and complications
      and reduce the surgeon specific impact. 

PMID- 24103861
TI  - Metabolic engineering of Escherichia coli and in silico comparing of
      carboxylation pathways for high succinate productivity under aerobic conditions.
AB  - A novel aerobic succinate production system was strategically designed that
      allows Escherichia coli to produce and accumulate succinate with high specific
      productivity under aerobic conditions. Mutations in the tricarboxylic acid cycle
      (sdhA, iclR) and byproduct formation pathways (poxB, ackA-pta, mgsA) of E. coli
      were created to construct the glyoxylate cycle and oxidative branch of the TCA
      cycle for aerobic succinate production. Strain ZJG13 (DeltasdhA, DeltaackA-pta,
      DeltapoxB, DeltamgsA, DeltaiclR) exhibited normal growth behavior and accumulated
      succinate with an average specific productivity of 0.50mmolg CDW(-1)h(-1) during
      the fermentation. The glyoxylate shunt operon aceKBA was overexpressed by
      introducing plasmid pT9aceKAB to ZJG13; the resulting strain had minor effect on
      productivity improvement. To fully understand the effect of the carboxylation
      reactions on succinate production, three reactions catalyzed by pyruvate
      carboxylase (PYC), malic enzyme (MAEA) and phosphoenolpyruvate carboxylase (PPC)
      were analyzed by a Computational Approach for Strain Optimization aiming at high
      Productivity (CASOP). Based on the CASOP analysis, carboxylation reaction
      catalyzed by PYC was the most suitable one to obtain high productivity. When pyc
      was overexpressed in ZJG13, the specific succinate productivity further increased
      to 0.76mmolg CDW(-1)h(-1). Fed-batch culture of the strain ZJG13/pT184pyc led to
      a titer of 36.1g/L succinate, with a specific productivity of 2.75mmolg CDW(-1)h(
      1) which stands for the highest value among currently reported aerobic bacterial
      succinate producers. These results indicate that the CASOP strategy is useful as
      a guiding tool for the rational strain design with high productivity. 

PMID- 24103860
TI  - Diabetes risk factors, diabetes risk algorithms, and the prediction of future
      frailty: the Whitehall II prospective cohort study.
AB  - OBJECTIVE: To examine whether established diabetes risk factors and diabetes risk
      algorithms are associated with future frailty. DESIGN: Prospective cohort study.
      Risk algorithms at baseline (1997-1999) were the Framingham Offspring, Cambridge,
      and Finnish diabetes risk scores. SETTING: Civil service departments in London,
      United Kingdom. PARTICIPANTS: There were 2707 participants (72% men) aged 45 to
      69 years at baseline assessment and free of diabetes. MEASUREMENTS: Risk factors
      (age, sex, family history of diabetes, body mass index, waist circumference,
      systolic and diastolic blood pressure, antihypertensive and corticosteroid
      treatments, history of high blood glucose, smoking status, physical activity,
      consumption of fruits and vegetables, fasting glucose, HDL-cholesterol, and
      triglycerides) were used to construct the risk algorithms. Frailty, assessed
      during a resurvey in 2007-2009, was denoted by the presence of 3 or more of the
      following indicators: self-reported exhaustion, low physical activity, slow
      walking speed, low grip strength, and weight loss; "prefrailty" was defined as
      having 2 or fewer of these indicators. RESULTS: After a mean follow-up of 10.5
      years, 2.8% of the sample was classified as frail and 37.5% as prefrail.
      Increased age, being female, stopping smoking, low physical activity, and not
      having a daily consumption of fruits and vegetables were each associated with
      frailty or prefrailty. The Cambridge and Finnish diabetes risk scores were
      associated with frailty/prefrailty with odds ratios per 1 SD increase
      (disadvantage) in score of 1.18 (95% confidence interval: 1.09-1.27) and 1.27
      (1.17-1.37), respectively. CONCLUSION: Selected diabetes risk factors and risk
      scores are associated with subsequent frailty. Risk scores may have utility for
      frailty prediction in clinical practice.

PMID- 24103862
TI  - Effects of FMN riboswitch on antioxidant activity in Deinococcus radiodurans
      under H2O2 stress.
AB  - The flavin mononucleotide (FMN) riboswitch is structured noncoding RNA domains
      that control gene expression by selectively binding FMN or sensing surrounding
      changes without protein factors, which are involved in the biosynthesis and
      transport of riboflavin and related compounds. We constructed the deletion mutant
      of FMN riboswitch to investigate its possible role in response to H2O2 stress in
      Deinococcus radiodurans. The results showed that the deletion of FMN riboswitch
      resulted in an obvious growth delay in D. radiodurans. Compared with the survival
      rate of 56% of D. radiodurans, only 40% of the mutant survived after treated with
      50 mM of H2O2, indicating that deletion of FMN riboswitch obviously increased the
      susceptibility to H2O2. Compared with the wild type R1 strain of D. radiodurans,
      FMN riboswitch knockout cells accumulated a higher level of intracellular
      reactive oxygen species (ROS) while their total catalase activity reduced
      significantly. Results from quantitative real-time PCR analysis implies
      structural alterations of in response to H2O2 challenge. Our data suggest a
      critical role of FMN riboswitch in the oxidation tolerance system of D.
      radiodurans.

PMID- 24103863
TI  - Holarrhena antidysenterica as a resistance modifying agent against Acinetobacter
      baumannii: Its effects on bacterial outer membrane permeability and efflux pumps.
AB  - Increasing rates of infections caused by multidrug resistant Acinetobacter
      baumannii (MDRAB) and extensively drug resistant A. baumannii (XDRAB) have caused
      the need for searching alternative agents. The purposed of this project was to
      search plant-derived natural products that act as resistant modifying agents
      (RMAs) against A. baumannii. In this study, we further evaluated the activity of
      Holarrhena antidysenterica that has been previously proposed as RMA of novobiocin
      for a model strain, A. baumannii ATCC 19606 on clinically isolated non-MDRAB,
      MDRAB, and XDRAB. Effects of H. antidysenterica on outer membrane permeability
      and efflux pumps of the pathogen were conducted to preliminary elucidate
      mechanisms of this resistant modifier. Novobiocin was selected as a model
      antibiotic because it is well-established as an effective agent against Gram
      positive pathogens. But, it possessed low level of antibacterial activity against
      Gram-negative pathogens due to an effective permeability barrier of these
      pathogens. H. antidysenterica ethanol extract possessed weak intrinsic
      antibacterial activity with minimum inhibitory concentration (MIC) more than 1000
      MUg/mL. The extract, at concentrations of 250, 125, and 62.5 MUg/mL, remarkably
      enhanced the inhibitory effects of novobiocin (1/4 * MIC; 1-4 MUg/mL) against
      XDRAB isolates. Synergistic effects of novobiocin at 1/4 * MIC and 1/8 * MIC in
      combination with H. antidysenterica either at 31.2, 15.6, or 7.8 MUg/mL against
      clinical isolates non-MDRAB, MDRAB, and XDRAB were evidenced for 80% of the
      combinations (189 out of 234 combinations). Although, no enhancement of the
      accumulation of ethidium bromide was observed after treated with H.
      antidysenterica, this plant extract weakened the outer membrane of the pathogen
      as indicated by an increase in the N-phenyl-1-naphthylamine uptake. Our results
      suggested that H. antidysenterica which primarily interrupts membrane
      permeability should be further investigated as a promising resistant modifier for
      A. baumannii.

PMID- 24103864
TI  - Jasmonate: A decision maker between cell death and acclimation in the response of
      plants to singlet oxygen.
AB  - Under stress conditions that bring about excessive absorption of light energy in
      the chloroplasts, the formation of singlet oxygen ( (1)O2) can be strongly
      enhanced, triggering programmed cell death. However, the (1)O2 signaling pathway
      can also lead to acclimation to photooxidative stress, when (1)O2 is produced in
      relatively low amounts. This acclimatory response is associated with a strong
      downregulation of the jasmonate biosynthesis pathway and the maintenance of low
      jasmonate levels, even under high light stress conditions that normally induce
      jasmonate synthesis. These findings suggest a central role for this phytohormone
      in the orientation of the (1)O2 signaling pathway toward cell death or
      acclimation. This conclusion is confirmed here in an Arabidopsis double mutant
      obtained by crossing the (1)O2-overproducing mutant ch1 and the jasmonate
      deficient mutant dde2. This double mutant was found to be constitutively
      resistant to (1)O2 stress and to display a strongly stimulated growth rate
      compared with the single ch1 mutant. However, the involvement of other
      phytohormones, such as ethylene, cannot be excluded.

PMID- 24103865
TI  - Fracture characteristics to distinguish between accidental injury and non
      accidental injury in dogs.
AB  - Non-accidental injury (NAI) refers to trauma arising from deliberate physical
      abuse and is increasingly recognised as an important differential diagnosis in
      veterinary medicine. Given the sensitivity and importance of identifying NAI,
      clinicians, pathologists, and veterinary forensic experts need clear scientific
      evidence to support their diagnosis. The aim of this study was to investigate
      fractures occurring in accidental and NAI in dogs by comparing the radiographic
      features of fractures in 19 dogs with abuse fractures and 135 dogs with
      accidental fractures. Radiographic findings indicated that the following five
      features should raise the index of suspicion of and support a diagnosis of NAI:
      (1) the presence of multiple fractures; (2) fractures occurring on more than one
      region of the body (forelimb, hindlimb, or axial); (3) transverse fractures; (4)
      fractures presenting at a later stage of healing (delayed presentation); and (5)
      multiple fractures at different stages of healing. Staffordshire bull terriers
      were over-represented in the NAI group. Many findings in this study correlate
      with patterns seen in human NAI fractures. However some aspects show significant
      differences, serving as a reminder that veterinary forensics cannot rely on data
      from existing human studies. 

PMID- 24103866
TI  - Control of medication in horses: detection time, withdrawal time and beyond.

PMID- 24103867
TI  - Evaluation of renal impairment in dogs after envenomation by the common European
      adder (Vipera berus berus).
AB  - Envenomation by the common European adder (Vipera berus berus) causes clinical
      renal injury in dogs. In this study, serum concentrations of albumin, creatinine,
      total protein and urea were measured in 32 dogs bitten by adders. Urinary
      creatinine, protein, and retinol binding protein 4 concentrations, and the
      activities of gamma-glutamyl transpeptidase (GGT) and alkaline phosphatase (ALP),
      were measured in 32 affected dogs and 23 healthy controls. Clinical assessment
      was conducted with a grading scale and a renal function score was applied to
      classify dogs based on laboratory findings. Urinary protein:creatinine,
      GGT:creatinine and ALP:creatinine ratios appear to be useful in evaluating renal
      impairment in dogs with adder envenomation. Increasing kidney function score was
      correlated with increased urinary ALP:creatinine and GGT:creatinine ratios. 

PMID- 24103868
TI  - [The clinical characteristics and prognostic analysis of 147 cases of diffuse
      large B-cell lymphoma].
AB  - OBJECTIVE: To investigate the relationship between the clinical features,
      pathogenesis, immunophenotype, different classification models and prognosis in
      Chinese patients with diffuse large B-cell lymphoma (DLBCL). METHODS: A total of
      147 patients with DLBCL who were treated with CHOP-like or R-CHOP were subjected
      to analysis. Standard two-step Envision method of immunohistochemical staining
      was used to assess the expression of CD10, Bcl-6, MUM1, FOXP1, GCET1, CD5, Bcl-2,
      Ki-67, then according to Hans algorithm, Choi algorithm and Molecular markers, we
      compared the differences of their prognoses. RESULTS: (1) Kaplan-Meier univariate
      analysis of the clinical data of 147 DLBCL patients found that the 3-year overall
      survival (OS) rates were better in early stage (P=0.032), low IPI score
      (P=0.001), less than one extranodal involvement (P=0.014), and complete remission
      (P<0.01). The prognoses had no significant difference in terms of gender, age,
      LDH, B symptoms and treatment options (P value> 0.05). (2 )For Hans model, GCB
      group had 42 cases, the ABC group 85 cases; GCB were 47 cases, ABC 80 cases
      (according to Choi model). Choi model suggested GCB subtype showed much better
      prognosis than ABC subtype (P=0.047), while Hans model shed no statistically
      significant difference (P=0.285). (3) Ki-67 of 75% was found to significantly
      discriminate patients with good or bad prognosis. In R-CHOP group at the same
      time, low Ki-67 (P=0.017) and CD5-negative groups (P=0.012) were better. Cox
      proportional hazards regression model showed that IPI score (P=0.002) and Ki-67
      (P=0.019) were independent adverse prognostic factors. CONCLUSION: The Ann Arbor
      stage, IPI score, extranodal involvement status and Ki-67 were significantly
      associated with prognosis .Compared to Hans algorithm, Choi had an advantage to
      predict the different prognosis between subtypes, and ABC group had poor outcome.
      Finally, both Ki-67 and IPI score were independent adverse prognostic factors.

PMID- 24103869
TI  - [Dexamethasone and vorinostat cooperatively promote differentiation and apoptosis
      in Kasumi-1 leukemia cells through ubiquitination and degradation of AML1-ETO].
AB  - OBJECTIVE: To probe the effects of dexamethasone (DEX) combined with histone
      deacetylase (HDAC) inhibitor vorinostat on inhibiting proliferation and inducing
      differentiation and apoptosis in Kasumi-1 leukemia cells, and its possible
      mechanisms in order to provide a theoretical basis for the treatment of AML1-ETO
      positive AML. METHODS: The cell survival, differentiation and apoptosis rates
      were tested by MTT or flow cytometry analysis after Kasumi-1 cells were treated
      by DMSO, DEX (20 nmol/L), vorinostat (1 MUmol/L) or DEX (20 nmol/L) in
      combination with vorinostat (1 MUmol/L). WB and IP-WB were performed to detect
      AML1-ETO and its ubiquitination. RESULTS: Treatment with the combination of DEX
      and vorinostat for 48 h led to statistically significant differences of inhibited
      proliferation [(42.06+/-8.20)%], increased differentiation [(52.83+/-8.97)%] and
      apoptosis [(52.92+/-2.53)%] of Kasumi-1 cells when compared with vorinostat
      [(33.82+/-9.41)%, (43.93+/-9.04)% and (42.98+/-3.01)%, respectively], DEX
      [(17.30+/-3.49)%, (22.53+/-4.51)% and (19.57+/-2.17)%, respectively] or control
      [(6.96+/-0.39)%, (21.73+/-2.03)% and (6.96+/-0.39)%, respectively]. Also
      significant ubiquitination and decreased AML1-ETO protein in Kasumi-1 cells after
      the combination treatment over single agent or control were observed. CONCLUSION:
      The results indicated that DEX and vorinostat could synergistically inhibit the
      Kasumi-1 cells proliferation, induce Kasumi-1 cells differentiation and apoptosis
      through ubiquitination and degradation of AML1-ETO.

PMID- 24103870
TI  - [Reconstitution kinetics of T helper cells subsets post unmanipulated allogeneic
      blood and marrow transplantation].
AB  - OBJECTIVE: To compare the differences of the T helper cell reconstitution
      kinetics between HLA matched or HLA mismatched allo-HSCT through exploring the
      reconstitution kinetics of CD4+ CD25+Foxp3+ cells (CD4+ Treg), CD8+CD25+Foxp3+
      cells (CD8+Treg), CD4+CD25-CD127+ conventional T cells (Tcon) and the secretion
      of IL-17a and IFN-gamma in CD4+ T cells (Th17 and Th1 cells) or CD8+ T cells
      (Tc17 and Tc17 cells) post allogeneic hematopoietic stem cells transplantation
      (allo-HSCT). METHODS: From December 2011 to October 2012, the peripheral blood
      (PB) of 20 patients undergoing HLA matched (10 patients) or mismatched (10
      patients) allo- HSCT without acute graft-versus-host disease (aGVHD) and of 10
      related healthy donors were collected to analyze the expression of CD25+Foxp3+,
      IL-17a, IFN-gamma and CD127 expression through 8-colour Flow cytometer. RESULTS:
      (1) The reconstitution kinetics of CD3+ T cells, CD4+ T cells, CD8+ T cells
      absolute numbers were comparable within 2 month post HLA matched and mismatched
      transplantation. (2)The absolute numbers of CD4+ Treg cells[+30 d, 8.46 (0.36
      27.41) cells/MUl 1.10 (0.04-8.03) cells/MUl, P<0.05; +60 d, 8.50 (1.16-36.20)
      cells/MUl vs 2.73 (0.34-6.84) cells/MUl, P<0.05], Tcon cells[+30 d, 72.69 (3.85
      211.73) cells/MUl vs 13.41 (0.48-96.17) cells/MUl, P<0.05; +60 d, 100.85 (16.28
      267.20) cells/MUl vs 47.75 (6.34-143.04) cells/MUl, P<0.05], as well as Th17
      cells[+30 d, 2.34 (0.02-6.87) cells/MUl vs 0.20 (0.02-1.34) cells/MUl, P<0.05; +
      60 d, 1.90 (0.36- 7.82) cells/MUl vs 0.46 (0.03-1.39) cells/MUl, P<0.05]and Tc17
      cells[+ 30 d, 1.08 (0.07-15.03) cells/MUl vs 0.25 (0.01- 0.81) cells/MUl,
      P<0.05;+60 d, 1.85 (0.63-26.57) cells/MUl vs 0.46 (0.01-3.66) cells/MUl,
      P<0.05]within 2 month post HLA matched HSCT were significantly higher than those
      post HLA- mismatched HSCT. However, the absolute numbers of Th1 cells or Tc1
      cells within 2 month post HLA-matched or HLA-mismatched HSCT were comparable. (3)
      The ratio of Th1 and Th17 cells, or the ratio of Tc1 and Tc17 cells were
      significantly higher within 2 month post HLA-mismatched allo-HSCT compared to
      those post HLA-matched HSCT. CONCLUSION: The reconstitution kinetics of T helper
      cells subset were different at early stage post HLA-matched or HLA-mismatched
      allo-HSCT, which might be help to explain the different rate or the different
      involved organ of the acute graft-versus-host diseases (aGVHD) post HLA-matched
      or -mismatched allo-HSCT.

PMID- 24103871
TI  - [Congenital afibrinogenemia caused by a novel insertion mutation in the FGB
      gene].
AB  - OBJECTIVE: To investigate the genetic defect and its mechanism in a patient with
      congenital afibrinogenemia. METHODS: The plasma fibrinogen activity and antigen
      of the patient was determined using the Clauss method and immuno-nephelometric
      assay, respectively. Genomic DNA was isolated from peripheral blood of the
      proband and his related family members. All exons and exon-intron boundaries of
      the three fibrinogen genes (FGA, FGB, FGG) were amplified by PCR followed by
      direct sequencing. Thrombin fibrin aggregation curve were detected in the plasma
      of the patient. Wild-type and mutation type fibrinogen vectors were constructed,
      and then transfected into COS-7 cells. The wild-type and mutant proteins from the
      culture media and cell lysates were tested by Western blot and ELISA. RESULTS:
      APTT, PT, TT were significantly longer in the proband. Plasma fibrinogen activity
      and antigen of the patient could not be detected using the Clauss method and
      immuno-nephelometry, respectively. Gene analysis revealed that a novel homozygous
      GTTT insertion between nucleotides 2833 and 2834 in FGB exon 2 in the proband.
      The proband's father, mother, brother and son were heterozygous. The
      polymerization curves of the patient did not show a lag phase or final turbidity,
      compared with the normal controls. Western blot analysis showed the lack of
      complete half-molecules of the fibrinogen molecule and fibrinogen in patient's
      plasma under non-reducing conditions. It also could not detect the truncated
      Bbeta chain under reducing conditions. Abnormal fibrinogen molecule (molecule
      weight>340 000) were found in transfected COS-7 cells by Western blot, which
      indicated that the mutation caused the abnormal intracellular fibrinogen molecule
      assembly. The fibrinogen band was absent in culture media transfected by the
      mutation. Fibrinogen levels of mutant fibrinogen were no significant different
      from those of wild-type fibrinogen in cell lysates by ELISA analysis [(2.47 +/-
      0.30) MUg/ml vs (2.65+/-0.60) MUg/ml, P=0.0889]; However, the levels of the
      mutant fibrinogen were statistically significant lower than those of wild type
      fibrinogen in culture media [(0.01 +/- 0.01) MUg/ml vs (3.80+/-0.80) MUg/ml,
      P=0.0001]. CONCLUSION: Congenital afibrinogenemia was caused by this frameshift
      mutation in exon 2 of FGB. This novel mutation impaired fibrinogen assembly and
      secretion.

PMID- 24103872
TI  - [Establishment of a high efficient human coagulation factor VIII eukaryotic
      expression system using lentiviral vector].
AB  - OBJECTIVE: To establish a high efficient human coagulation factor VIII (FVIII)
      eukaryotic stable expression system using lentiviral vector, and determine its
      biosafety. METHODS: Lentiviral transfer plasmid carrying human B-domain-deleted
      FVIII(BDDhFVIII)-IRES-GFP(BDDhFVIII/pXZ9)or IRES-GFP(pXZ9) was constructed.
      Lentivirus particles were produced by transiently co-transfected 3-plasmids into
      293FT cells and further concentrated via ultracentrifugation. CHO cells were
      infected, 72h later, the FVIII antigen (FVIII:Ag) concentration in the medium was
      examined by ELISA, the activity was detected via one stage coagulation,and the
      transcription of FVIII in the infected CHO cells was determined by RT-PCR.Virus
      infection ability in the medium and the gag gene in CHO cells were determined to
      evaluate the model's biosafety. RESULTS: Lentiviral transfer plasmid BDDhFVIII
      IRES-GFP(BDDhFVIII/pXZ9)carrying human B-domain-deleted FVIII or IRES-GFP (pXZ9)
      was successfully constructed, and high titer lentiviruses has been prepared. The
      lentivirus could infect CHO cells efficiently, after an additional 72 h, the
      FVIII:Ag concentration had up to (1724.9+/-283.7) mU/ml, the FVIII:C level
      increased to (10.58+/-1.55)%, and transcripts of BDDhFVIII mRNA could be measured
      by RT-PCR. Neither the gag gene nor the virus in the supernatant was detected.
      CONCLUSION: Lentivirus-mediated human coagulation factor VIII could be expressed
      efficiently in CHO cells. The system couldn't produce offspring virus, proving a
      good biosafety.

PMID- 24103873
TI  - [Effects of imatinib mesylate on the levels of endocrine hormones].
AB  - OBJECTIVE: To measure the levels of hormones in chronic myelogenous leukemia
      (CML) patients receiving imatinib mesylate (IM) and evaluate the effects of IM on
      endocrine system. METHODS: 69 patients with CML while taking IM were enrolled and
      a total of 86 peripheral blood samples were detected. The levels of total
      triiodothyronine (TT3), total tetraiodothyronine (TT4), thyroid stimulating
      hormone (TSH), testosterone, progesterone, estradiol (E2), plasma total cortisol
      (PTC) at 8:00-10:00 am measured. Concentration of hormones in different groups
      were measured to evaluate the effects of IM on endocrine system and relationships
      with its administration duration, plasma concentration and clinical symptoms.
      RESULTS: (1) Of the 7 types of hormones, an elevation of TSH level was found in
      14 patients (20.3%), a decrease of TT3 and testosterone in 8 patients (11.6%) and
      8 males (18.6%), respectively. (2) A significant decline of TT3 and testosterone
      was observed in all patients divided by different administration duration.
      Negative correlation was seen between TT3 level and duration of administration
      (r=-0.273, P=0.010), which was also found for testosterone (r=-0.302, P=0.025).
      (3) There was no correlation between serum levels of the seven hormones and
      concentration of IM. CONCLUSION: IM affect the levels of thyroid and sex hormones
      in some patients with clinical manifestations: a decrease of TT3, testosterone
      and testosterone, an increase of TSH, which have relationship with the duration
      of administration.

PMID- 24103874
TI  - [Analysis of a hereditary protein C deficient consanguineous pedigree caused by
      Phe139Val homozygous mutation].
AB  - OBJECTIVE: To analyze genetic mutation and explore its molecular pathogenesis for
      an hereditary protein C (PC) deficient consanguineous pedigree. METHODS: The
      pedigree included three generations and contained eight members. PC activity
      (PC:A), PC antigen (PC:Ag) and other coagulant parameters were detected for all
      family members. Protein C gene (PROC) include all the exons and intron exon
      boundaries were amplified by PCR for the proband, then analyzed by direct
      sequencing. Mutation sites were detected for the other family members. RESULTS:
      The PC:A and PC:Ag in the proband plasma were 20% (normal range 70% -140%) and
      13.2% (normal range 70%-130%). A homozygous missense mutation g.6128T>G in exon 7
      resulting in Phe139Val was identified in the proband. The PC:A and PC:Ag in her
      younger brother were 31% and 18.90%, Phe139Val homozygous was also found. The
      left family members were heterozygous for Phe139Val. CONCLUSION: Phe139Val
      homozygous missense mutation in exon 7 of PROC caused serious hereditary protein
      C deficiency. We speculated that homozygous mutation might be resulted from this
      consanguineous marriage.

PMID- 24103875
TI  - [The relationship of telomere and telomerase activity with outcome of aplastic
      anemia after immunosuppressive therapy].
AB  - OBJECTIVE: To observe the changes of telomere length and telomerase activity in
      patients with aplastic anemia (AA), and relationship with immunosuppressive
      therapy (IST) efficacy, to explore the pathogenesis of AA and the role of
      telomere length in evaluating immunosuppressive therapy efficacy. METHODS: 71
      cases of AA patients between September 2010 and March 2013 were enrolled into
      this study. 3 ml peripheral blood specimens from this cohort of patients were
      collected to test the telomere length in peripheral blood mononuclear cell
      (PBMNC) with flow-FISH and detect telomerase activity with TRAP-PCR-ELISA method.
      RESULTS: Telomere length and age showed negative correlation (b=-0.387, P=0.001)
      in normal control, NSAA and SAA + VSAA groups, telomere length became shorter
      with the growth of age, and normal control group telomere length decreased along
      with the age growth slightly greater than the other two groups (NSAA, SAA+VSAA).
      Besides the effect of age on telomere length, no significant difference was
      observed between NSAA and SAA+VSAA groups (P=0.573), and NSAA, SAA+VSAA (30.957
      +/- 4.502,29.510 +/- 5.911)groups were significantly shorter than normal control
      group (51.086+/-10.844) (P<0.01). Telomere length in NR group (25.357+/-4.848)was
      significantly lower than normal control group (51.086 +/- 10.844) (P=0.005),
      telomere length in CR(32.808 +/- 4.685)/PR groups (30.334+/-4.464) compared with
      normal control group had no significant difference (P=0.517, P=0.254). Telomere
      length below 29.21% obviously decreased outcomes of IST. Telomerase activity had
      significant difference (chi2=20.385, P<0.01). The telomerase activity had no
      significant difference in terms of age and gender in three groups, multiple
      comparison found that telomerase activities in SAA + VSAA (0.324+/-0.178)
      (P<0.01), and NSAA (0.234+/-0.175) groups (P=0.002) were significantly higher
      than normal control group (0.107+/-0.083). CONCLUSION: Telomere length of PBMNC
      in AA patients was significantly shortened than normal control group with
      telomerase activity increased, and telomere shorted more apparently in NR group,
      these patients should adjust the treatment as early as possible. Telomeres could
      predict the curative effect of IST.

PMID- 24103876
TI  - [The expression and clinical significance of miR-203 in pediatric acute
      leukemia].
AB  - OBJECTIVE: To investigate the methylation, expression and clinical significance
      of miR-203 in pediatric acute leukemia. METHODS: The methylation status of miR
      203 promoter CpG islands was detected with methylation-specific polymerase chain
      reaction. The expression of miR-203 was detected by Taqman real- time
      quantitative polymerase chain reaction. And the clinical significance of miR-203
      in pediatric acute leukemia (ALL) was also analyzed. RESULTS: The promoter of miR
      203 was unmethylated in all of 31 pediatric acute lymphoblastic leukemia, all of
      15 pediatric acute myeloid leukemia (AML) and all of 23 controls. The relative
      expression levels of miR-203 in controls, pediatric acute leukemia, ALL and AML
      were 16.93+/-6.31, 48.97+/-10.38, 55.88+/-12.91, 24.28+/-9.10 respectively. The
      results indicated that miR-203 was significantly up- regulated in pediatric acute
      leukemia (P=0.011) and ALL (P=0.009), not in pediatric AML (P=0.514) compared
      with control. The expression of miR-203 was significantly related with the
      gender, immunophenotype, chromosome, fusion gene, BCR-ABL, SIL-TAL1 and
      prednisone experiment in pediatric ALL and the gender, chromosome, fusion gene,
      SIL-TAL1 in pediatric acute leukemia (P<0.05). And in risk stratification
      pairwise comparisons, the expression of miR-203 in the medium-risk and high-risk
      groups appeared significantly different (P=0.022). CONCLUSION: miR-203 may not be
      regulated with methylation mechanism in pediatric acute leukemia. miR- 203 may be
      a protooncogene involved in the formation of pediatric acute leukemia and ALL.
      Further analyses indicated that high expression of miR-203 may be associated with
      poor prognosis of pediatric ALL and acute leukemia.

PMID- 24103877
TI  - [Effects of immature dendritic cells to express CCR7 on graft-versus-host disease
      in allogeneic bone marrow transplant mouse model].
AB  - OBJECTIVE: To investigate the effects of immature dendritic cells (imDC)
      expressing chemokine receptor-7 (CCR7) on acute graft-versus-host disease (aGVHD)
      in allogeneic bone marrow transposed (allo-BMT) mouse model. METHODS: We
      constructed the lentiviral vectors carrying mouse CCR7 gene and infect imDC
      effectively in vitro. GVHD model was established with C57BL/6(H-2b) donor mice
      and BALB/c (H-2d) recipient mice. After irradiation, recipients were injected
      with donor bone marrow and spleen cells along with CCR7-modified dendritic cells.
      Mice were randomized into irradiation, transplant control, pXZ9-imDC (empty
      vector control) and CCR7-imDC groups. Survival, GVHD score, histopathological
      analysis and plasma levels of inflammatory cytokines were observed. RESULTS: The
      mean survival in irradiation, transplantation, pXZ9-imDC and CCR7-imDC groups
      were (8.20+/-1.48)d, (12.20+/-2.78)d, (20.70+/-6.01)d and (27.5+/-7.55)d
      respectively. The survival in CCR7- imDC group was significantly improved
      compared with other groups (P<0.05). GVHD scores in transplantation, pXZ9-imDC
      and CCR7-imDC groups were (6.90+/-1.66), (5.60+/-0.97) and (4.10+/-1.79)
      respectively. CCR7-imDC group had significantly lower GVHD score and minor tissue
      damages shown by histopathological analysis than the other groups. Plasma IFN
      gamma level increased and reached the peak at +10 day in transplant group, while
      it gradually decreased in pXZ9-imDC and CCR7-imDC groups, and then reached the
      nadir at +20 day post-allo-BMT, with the lowest level in CCR7-imDC group
      (P<0.01). Plasma IL-4 decreased in transplant group, while it gradually increased
      in pXZ9-imDC and CCR7-imDC groups and reached the highest level at + 10 day in
      CCR7- imDC group (P<0.01). The 95%-100% of H-2b positive cells in recipient mice
      on + 30 day post-allo-BMT demonstrated the complete donor- type implantation.
      CONCLUSION: Genetically modified immature DC by CCR7 gene could alleviate damages
      by GVHD and prolong survival of recipient mice after allo-BMT.

PMID- 24103878
TI  - [Alterations of connexin 43 expression and SDF-1alpha secretion of bone marrow
      mesenchymal stem cells co-cultured with myeloma cells].
AB  - OBJECTIVE: To construct a co- culture system of mesenchymal stem cells (MSC) and
      multiple myeloma (MM) cells and investigate the alterations of connexin 43 (CX43)
      expression and stromal derived growth factor (SDF)- 1alpha secretion of MSC.
      METHODS: CX43 expression and SDF- 1alpha secretion of MM cell lines (RPMI8226)
      and human primary MM cells were analyzed by western blot and immunofluorescence.
      Western blot, RT- PCR and immunofluorescence were employed to detect the
      alterations of CX43 expression and distribution in MSC directly and indirectly co
      cultured with myeloma cells. Lucifer yellow dye spread was utilized to evaluate
      gap junctional intercellular communication (GJIC) between co- cultured MSC.
      Transwell was applied to study the transmigration of RPMI8266 induced by MSC
      under the condition of 18alpha- glycyrrhetinic acid (18alpha-GA). The level of
      SDF- 1alpha was detected by EILSA. RESULTS: RPMI8266, U266 and one-third primary
      MM cells expressed CX43 at low or moderate levels. CX43 wasn't expressed in XG- 4
      and XG- 7 cells but highly expressed in MSC. The expressions of CX43 mRNA of MSC
      were up- regulated after directly and indirectly co- cultured with RPMI8226, 1.36
      and 2.10 times that of MSC cultured alone respectively. Western blot analysis
      showed that CX43 protein expression of MSC was also up-regulated, mainly
      distributed in cytoplasm. Lucifer yellow dye spread showed that GJIC was up
      regulated in MSC. SDF-1alpha concentration in supernatant of MSC directly and
      indirectly co-cultured with RPMI8226 were (373.02+/-10.11)pg/ml and (309.71+/
      10.71)pg/ml respectively, which were higher than that of MSC cultured alone
      (237.84+/-9.23)pg/ml (P<0.01), and could be inhibited by 18alpha-GA [(237.84+/
      9.23)pg/ml and (94.31+/-6.44)pg/ml] respectively (P<0.01). 18alpha-GA could
      inhibit the transmigration of RPMI8226 induced by MSC, decrease from (8.00+/
      0.67)% to (4.82+/-0.19)%. CONCLUSION: CX43 expression of MSC was up-regulated
      after directly and indirectly co-cultured with MM cells, which could improve the
      level of SDF-1alpha secretion of MSC. GJ inhibitor could downregulate SDF-1alpha
      secretion of MSC and inhibit the transmigration of MM cells induced by MSC.

PMID- 24103879
TI  - [Inhibitory effects of gamma secretase inhibitor on human multiple myeloma
      xenograft mouse model].
AB  - OBJECTIVE: To explore the tumor growth inhibition of gamma secretase inhibitor
      MRK003 on human multiple myeloma xenograft mice by inhibition of AKT and Notch1
      expression. METHODS: NOD/SCID mice were injected with human multiple myeloma cell
      lines RPMI8226 to establish a xenograft mouse model. Mice were randomized into
      two groups:the experimental group were injected with MRK003 at a dose of 5 mg* kg
      1*d-1 for 14 days; the inhibitor was replaced by an equal saline in the control
      group. Mice were sacrificed by cervical dislocation on the next day after the
      last injection and tumor tissue was removed to detect the expression of Notch1
      and AKT by immunohistochemistry. RESULTS: After subcutaneous injection with
      RPMI8226, mice had tumor formation in 5-7 days and the largest tumor block in 10
      12 days. Before RPMI8226 injection, the mean sizes of tumor block in the
      experimental and the control groups were 509.2 mm3, 511.2 mm3(P>0.05). 9 days
      after injection, the mean sizes of tumor tissue in the experimental and the
      control groups were 636.6 mm3, 691.2 mm3(P<0.01). On the next day after the last
      injection, the tumor sizes of the experimental and the control groups were 683.5
      mm3 and 1798.7 mm3(P<0.01). The size of tumor block in the experimental group was
      significantly smaller than that of the control group(P<0.01).
      Immunohistochemistry staining showed that the positive expression rates of
      Notch1(11.1%, P<0.01) and AKT(13.3%, P<0.01) in experimental group were
      significantly decreased compared with the control group(Notch1: 95.6%; AKT:
      93.3%). Western blot results showed that Notch1 and AKT protein in experimental
      group were significantly lower than those in the control group. CONCLUSION:
      MRK003 could inhibit the tumor growth of human multiple myeloma xenograft mice by
      downregulated expression of Notch1 signaling pathway.

PMID- 24103880
TI  - [Mechanisms of arsenic trioxide induced apoptosis in Karpas299 cell].

PMID- 24103881
TI  - [The expression of IL-21 in immune thrombocytopenic purpura and its effect on
      proliferation of peripheral blood mononuclear cells].

PMID- 24103882
TI  - [Dynamic analysis of the pathological intestine and T cell activation from
      mesenteric lymph nodes in GVHD mouse].

PMID- 24103883
TI  - [Multicenter, retrospective study of biapenem in the treatment of 1090 cases with
      hematological diseases complicated with infections].

PMID- 24103884
TI  - [Gene therapy for hemophilia B].

PMID- 24103885
TI  - [The impact of anti- HLA antibody on the outcome of allogeneic hematopoietic stem
      cell transplantation].

PMID- 24103886
TI  - [Chinese guidelines for diagnosis and treatment of diffuse large B cell
      lymphoma(2013)].

PMID- 24103887
TI  - [Chinese guidelines for diagnosis and treatment of follicular lymphoma(2013)].

PMID- 24103888
TI  - Infant cortisol and behavioral habituation to weekly maternal separations: links
      with maternal prenatal cortisol and psychosocial stress.
AB  - INTRODUCTION: Our aim was to examine infants' behavioral and physiological stress
      responses to three weekly maternal separations, in relation to maternal prenatal
      psychosocial stress and cortisol. The hypothesis was that more prenatal stress
      and higher cortisol concentrations would predict smaller decreases in negative
      behavior and cortisol responses over the separations (i.e. less habituation).
      METHODS: General and pregnancy-related feelings of stress and anxiety, as well as
      circadian cortisol levels, were measured in 107 mothers in the third trimester of
      pregnancy. At 9 months of age, infants were subjected to three weekly 1-h
      maternal separations in their homes. Salivary cortisol was obtained from the
      infants prior to the separation and at 35, 75, and 90 min after the mother had
      left. For each separation, the area under the curve to the ground (AUCg) was
      calculated to measure the infants' cortisol response, and the sum of the time
      spent crying and fussing was calculated to measure the infants' behavioral
      response. RESULTS: Maternal pregnancy cortisol awakening response (CAR)
      significantly predicted infants' cortisol and behavioral responses. A lower CAR
      was related to a decreasing cortisol response, while a higher CAR was related to
      a stable cortisol response over all separations, as well as to less crying and
      fussing over all separations. CONCLUSIONS: Increased maternal prenatal stress, as
      measured by the CAR, is related to altered behavioral and cortisol responses to a
      repeated stressor in the 9-month-old infant. These responses might result in
      prolonged periods with high cortisol levels that may affect the child's
      development.

PMID- 24103889
TI  - Corticotropin (ACTH)-reactive immunoglobulins in adolescents in relation to
      antisocial behavior and stress-induced cortisol response. The TRAILS study.
AB  - Elevated levels of corticotropin (ACTH)-reactive immunoglobulins (ACTH IgG) were
      found in males with conduct disorder, suggesting their involvement in the biology
      of antisocial behavior. We first aimed to confirm these findings in a large
      general population sample of adolescents. Secondly, we studied the association
      between ACTH IgG levels and hypothalamic-pituitary-adrenal (HPA) axis response to
      stress. Free and total ACTH IgG levels were measured in sera of 1230 adolescents
      (15-18 years). HPA axis activity was determined by measuring salivary cortisol
      before, during, and after a social stress test. Antisocial behavior was assessed
      using the Antisocial Behavior Questionnaire. ACTH peptide and IgG affinity
      kinetics for ACTH were assayed in a subsample of 90 adolescents selected for high
      or low ACTH IgG levels. In boys, higher total ACTH IgG levels were associated
      with higher antisocial behavior scores (beta=1.05, p=0.04), especially at high
      levels of free ACTH IgG. In girls, antisocial behavior was associated with low
      free ACTH IgG levels (beta=-0.20, p=0.04). Stress-induced cortisol release was
      associated with free ACTH IgG in boys (betaareaunderthecurve=-0.67, p<0.01), and
      with total ACTH IgG in girls (betarecovery=0.84, p=0.05). The affinity kinetics
      assay showed that ACTH IgG association rates were lower in both boys and girls
      with high ACTH IgG levels. These data show that ACTH IgG levels are related to
      antisocial behavior and HPA axis response to stress in adolescents. The
      mechanisms behind these associations, including different ACTH binding properties
      of IgG in subjects with antisocial behavior, deserve further attention. 

PMID- 24103890
TI  - Peri-pubertal gonadotropin-releasing hormone agonist treatment affects sex biased
      gene expression of amygdala in sheep.
AB  - The nature of hormonal involvement in pubertal brain development has attracted
      wide interest. Structural changes within the brain that occur during pubertal
      development appear mainly in regions closely linked with emotion, motivation and
      cognitive functions. Using a sheep model, we have previously shown that peri
      pubertal pharmacological blockade of gonadotropin releasing hormone (GnRH)
      receptors, results in exaggerated sex-differences in cognitive executive function
      and emotional control, as well as sex and hemisphere specific patterns of
      expression of hippocampal genes associated with synaptic plasticity and endocrine
      signaling. In this study, we explored effects of this treatment regime on the
      gene expression profile of the ovine amygdala. The study was conducted with 30
      same-sex twin lambs (14 female and 16 male), half of which were treated with the
      GnRH agonist (GnRHa) goserelin acetate every 4th week, beginning before puberty,
      until approximately 50 weeks of age. Gene expression profiles of the left and
      right amygdala were measured using 8*15 K Agilent ovine microarrays. Differential
      expression of selected genes was confirmed by qRT-PCR (Quantitative real time
      PCR). Networking analyses and Gene Ontology (GO) Term analyses were performed
      with Ingenuity Pathway Analysis (IPA), version 7.5 and DAVID (Database for
      Annotation, Visualization and integrated Discovery) version 6.7 software
      packages, respectively. GnRHa treatment was associated with significant sex- and
      hemisphere-specific differential patterns of gene expression. GnRHa treatment was
      associated with differential expression of 432 (|logFC|>0.3, adj. p value <0.05)
      and 46 (p value <0.0.5) genes in the left and right amygdala, respectively, of
      female animals, relative to the reference sample which consisted of all a pooled
      sample from control and treated animals of both sexes. No genes were found to be
      differentially expressed as a result of GnRHa treatment in the male animals. The
      results indicated that GnRH may, directly and/or indirectly, be involved in the
      regulation of sex- and hemisphere-specific differential expression of genes in
      the amygdala. This finding should be considered when long-term peri-pubertal
      GnRHa treatment is used in children.

PMID- 24103891
TI  - Early social deprivation impairs pair bonding and alters serum corticosterone and
      the NAcc dopamine system in mandarin voles.
AB  - Early life stress has a long-term negative impact on emotion, learning, memory
      and adult sexual behavior, and these deficits most likely impair pair bonding.
      Here, we investigated whether early social deprivation (ED) affects the formation
      of pair bonds in socially monogamous mandarin voles (Microtus mandarinus). In a
      partner preference test (PPT), ED-reared adult females and males did not show a
      preference for their partner, spent more time exploring the cage of an unfamiliar
      animal and directed high levels of aggression toward unfamiliar animals. In
      social interaction test, ED increased exploring behavior only in females, but
      increased movement around the partner and reduced inactivity in both males and
      females. Three days of cohabitation did not alter serum corticosterone levels in
      ED-reared males, but increased corticosterone levels in males that received bi
      parental care (PC). Interestingly, serum corticosterone levels in ED- and PC
      reared females declined after cohabitation. ED significantly increased basal
      serum corticosterone levels in males, but had no effect on females. ED
      significantly up-regulated the levels of dopamine and the mRNA expression of
      dopamine 1-type receptor (D1R) in the nucleus accumbens (NAcc) in females and
      males. ED suppressed dopamine 2-type receptor mRNA (D2R) expression in females,
      but increased this in males. After three days of cohabitation, levels of D1R mRNA
      and D2R mRNA expression changed in opposite directions in PC-reared voles, but in
      the same direction in ED-reared males, and only the expression of D2R mRNA
      increased in ED-reared females. Our results indicate that early social
      deprivation inhibits pair bonding at adulthood. This inhibition is possibly
      associated with sex-specific alterations in serum corticosterone, levels of
      dopamine and mRNA expression of two types of dopamine receptors in the NAcc. 

PMID- 24103893
TI  - Diagnosing and managing Lyme disease.
AB  - All primary care providers should be familiar with the symptoms, diagnostic
      criteria, and treatments for Lyme disease. This tick-borne illness is increasing
      in incidence and geographic spread in the United States. 

PMID- 24103894
TI  - Updated guidelines for managing chronic kidney disease.
AB  - Chronic kidney disease (CKD) is the most costly disease covered by Medicare, and
      two common causes of CKD, diabetes and hypertension, are increasing worldwide.
      More than 60% of Americans will develop CKD in their lifetimes. This article
      reviews updated guidelines for managing CKD in primary care. 

PMID- 24103892
TI  - Viral and cellular requirements for the nuclear entry of retroviral
      preintegration nucleoprotein complexes.
AB  - Retroviruses integrate their reverse transcribed genomes into host cell
      chromosomes as an obligate step in virus replication. The nuclear envelope
      separates the chromosomes from the cell cytoplasm during interphase, and
      different retroviral groups deal with this physical barrier in different ways.
      Gammaretroviruses are dependent on the passage of target cells through mitosis,
      where they are believed to access chromosomes when the nuclear envelope dissolves
      for cell division. Contrastingly, lentiviruses such as HIV-1 infect non-dividing
      cells, and are believed to enter the nucleus by passing through the nuclear pore
      complex. While numerous virally encoded elements have been proposed to be
      involved in HIV-1 nuclear import, recent evidence has highlighted the importance
      of HIV-1 capsid. Furthermore, capsid was found to be responsible for the viral
      requirement of various nuclear transport proteins, including transportin 3 and
      nucleoporins NUP153 and NUP358, during infection. In this review, we describe our
      current understanding of retroviral nuclear import, with emphasis on recent
      developments on the role of the HIV-1 capsid protein. 

PMID- 24103896
TI  - Evaluation of serogroup C and ACWY meningococcal vaccine programs: projected
      impact on disease burden according to a stochastic two-strain dynamic model.
AB  - OBJECTIVE: Advisory committees in Canada and the United States have updated
      recommendations for quadrivalent meningococcal conjugate vaccines against
      serogroups A, C, W135, and Y. Our objective was to evaluate optimally effective
      meningococcal vaccination policies using a stochastic dynamic model. Canada was
      used as an example. METHODS: Our stochastic dynamic model of Neisseria
      meningitidis (Nm) transmission in an age-structured population assumed partial
      cross-immunity among two aggregated serogroup categories: 'AWY' containing A,
      W135, and Y; and 'Other' containing B, C, and ungroupable types. We compared the
      impact of monovalent C versus quadrivalent ACWY vaccination on Nm carriage and
      invasive meningococcal disease (IMD). Our model was parameterized with Canadian
      epidemiological and demographic data and employed probabilistic sensitivity
      analysis. RESULTS: Routine infant immunization at 12 months and boosting at 15
      years with a quadrivalent vaccine is projected to have the largest impact on
      total IMD incidence: a 74% reduction over 40 years. Routine infant immunization
      with a monovalent vaccine at 12 months only has much less impact and also
      generates strain replacement appearing after approximately ten years of
      continuous use. CONCLUSIONS: Immunizing infants at 12 months and boosting
      adolescents at 15 years with an ACWY vaccine is predicted to be most effective at
      reducing IMD incidence.

PMID- 24103897
TI  - Are community pharmacists equipped to ensure the safe use of oral anticancer
      therapy in the community setting? Results of a cross-country survey of community
      pharmacists in Canada.
AB  - PURPOSE: Oral anticancer agents offer significant benefits over parenteral
      anticancer therapy in terms of patient convenience and reduced intrusiveness.
      Oral anticancer agents give many cancer patients freedom from numerous hospital
      visits, allowing them to obtain their medications from their local community
      pharmacy. However, a major concern with increased use of oral anticancer agents
      is shift of responsibility in ensuring the proper use of anticancer agents from
      the hospital/clinical oncology team to the patient/caregiver and other healthcare
      providers such as the community pharmacists who may not be appropriately trained
      for this. This study assessed the readiness of community pharmacists across
      Canada to play this increased role with respect to oral anticancer agents.
      METHODS: Using a structured electronic mailing strategy, a standardized survey
      was mailed to practicing pharmacists in five provinces where community
      pharmacists were dispensing the majority of oral anticancer agents. In addition
      to collecting basic demographic and their practice setting, the survey assessed
      the pharmacists' knowledge regarding cancer therapy and oral anticancer agents in
      particular, their education needs and access to resources on oral anticancer
      agents, the quality of prescriptions for oral anticancer agents received by them
      in terms of the required elements, their role in patient education, and steps to
      enhance patient and personal safety. RESULTS: There were 352 responses to the
      survey. Only 13.6% of respondents felt that they had received adequate oncology
      education at the undergraduate level and approximately 19% had attended a
      continuing education event related to oncology in the past 2 years. Only 24% of
      the pharmacists who responded were familiar with the common doses of oral
      anticancer agents and only 9% felt comfortable educating patients on these
      medications. CONCLUSIONS: A substantial portion of community pharmacists in
      Canada lack a solid understanding of oral anticancer agents and thus are poorly
      equipped to play a major role in ensuring their appropriate use. More education
      and training on oral anticancer agents are urgently required.

PMID- 24103895
TI  - Safety and infectivity of two doses of live-attenuated recombinant cold-passaged
      human parainfluenza type 3 virus vaccine rHPIV3cp45 in HPIV3-seronegative young
      children.
AB  - BACKGROUND: Human parainfluenza virus type 3 (HPIV3) is a common cause of upper
      and lower respiratory tract illness in infants and young children. Live
      attenuated cold-adapted HPIV3 vaccines have been evaluated in infants but a
      suitable interval for administration of a second dose of vaccine has not been
      defined. METHODS: HPIV3-seronegative children between the ages of 6 and 36 months
      were randomized 2:1 in a blinded study to receive two doses of 105 TCID50 (50%
      tissue culture infectious dose) of live-attenuated, recombinant cold-passaged
      human PIV3 vaccine (rHPIV3cp45) or placebo 6 months apart. Serum antibody levels
      were assessed prior to and approximately 4-6 weeks after each dose. Vaccine virus
      infectivity, defined as detection of vaccine-HPIV3 in nasal wash and/or a>=4-fold
      rise in serum antibody titer, and reactogenicity were assessed on days 3, 7, and
      14 following immunization. RESULTS: Forty HPIV3-seronegative children (median age
      13 months; range 6-35 months) were enrolled; 27 (68%) received vaccine and 13
      (32%) received placebo. Infectivity was detected in 25 (96%) of 26 evaluable
      vaccinees following doses 1 and 9 of 26 subject (35%) following dose 2. Among
      those who shed virus, the median duration of viral shedding was 12 days (range 6
      15 days) after dose 1 and 6 days (range 3-8 days) after dose 2, with a mean peak
      log10 viral titer of 3.4 PFU/mL (SD: 1.0) after dose 1 compared to 1.5 PFU/mL
      (SD: 0.92) after dose 2. Overall, reactogenicity was mild, with no difference in
      rates of fever and upper respiratory infection symptoms between vaccine and
      placebo groups. CONCLUSION: rHPIV3cp45 was immunogenic and well-tolerated in
      seronegative young children. A second dose administered 6 months after the
      initial dose was restricted in those previously infected with vaccine virus;
      however, the second dose boosted antibody responses and induced antibody
      responses in two previously uninfected children.

PMID- 24103898
TI  - A curious case of oxaliplatin-induced neurotoxicity: recurrent, self-limiting
      dysarthria.
AB  - This report presents a unique case of oxaliplatin-induced neurotoxicity featuring
      acute, recurrent, self-limiting dysarthria following multiple subsequent
      infusions of oxaliplatin. A 65-year-old man started chemotherapy for metastatic
      pancreatic adenocarcinoma with oxaliplatin-irinotecan-leucovorin-5-fluorouracil
      (FOLFIRINOX). During the first and subsequent infusions of oxaliplatin, the
      patient developed episodes of dysarthria that lasted between 2 and 4 h after
      oxaliplatin infusions, followed by their complete and uneventful resolution. A
      thorough neurological examination showed no new neurologic deficits except for
      very fine tongue fasciculations. Recognizing this self-limiting toxic effect of
      oxaliplatin is important in order to avoid dose reductions that may affect
      clinical outcomes. 

PMID- 24103899
TI  - Trastuzumab therapy in breast cancer: To reload or not to reload?

PMID- 24103900
TI  - Severe hypoglycemia and cognitive decline in older people with type 2 diabetes:
      the Edinburgh type 2 diabetes study.
AB  - OBJECTIVE: People with type 2 diabetes are at increased risk of age-related
      cognitive decline and dementia. Hypoglycemia is a candidate risk factor, but the
      direction of association between episodes of severe hypoglycemia and cognitive
      decline in type 2 diabetes remains uncertain. RESEARCH DESIGN AND METHODS: In the
      Edinburgh Type 2 Diabetes Study, cognitive function was assessed in 831 adults
      with type 2 diabetes (aged 60-75 years) at baseline and after 4 years. Scores on
      seven neuropsychological tests were combined into a standardized general ability
      factor g. Self-reported history of severe hypoglycemia at baseline (history of
      hypoglycemia) and at follow-up (incident hypoglycemia) was recorded. RESULTS: A
      history of hypoglycemia was reported by 9.3% of subjects, and 10.2% reported
      incident hypoglycemia. Incident hypoglycemia was associated with poorer cognitive
      ability at baseline (age- and sex-adjusted odds ratio for lowest tertile of g
      2.04 [95% CI 1.25-3.31], P = 0.004). Both history of hypoglycemia and incident
      hypoglycemia were also associated with greater cognitive decline during follow-up
      (mean follow-up g adjusted for age, sex, and baseline g -0.25 vs. 0.03 [P = 0.02]
      and -0.28 vs. 0.04 [P = 0.01], respectively), including after addition of
      vascular risk factors and cardiovascular and microvascular disease to the models
      (-0.23 vs. 0.03 [P = 0.04] and -0.21 vs. 0.05 [P = 0.03], respectively).
      CONCLUSIONS: The relationship between cognitive impairment and hypoglycemia
      appeared complex, with severe hypoglycemia associated with both poorer initial
      cognitive ability and accelerated cognitive decline.

PMID- 24103901
TI  - Prevention of type 2 diabetes in subjects with prediabetes and metabolic syndrome
      treated with phentermine and topiramate extended release.
AB  - OBJECTIVE To evaluate over 108 weeks the effect of phentermine and topiramate
      extended release (PHEN/TPM ER) treatment on progression to type 2 diabetes and/or
      cardiometabolic disease in subjects with prediabetes and/or metabolic syndrome
      (MetS) at baseline. RESEARCH DESIGN AND METHODS Subanalysis of a phase 3,
      randomized, placebo-controlled, double-blind study of overweight/obese subjects
      (BMI >=27 to <=45 kg/m(2)) with two or more comorbidities. Subjects were
      randomized to placebo, PHEN 7.5 mg/TPM ER 46 mg (7.5/46), or PHEN 15 mg/TPM ER 92
      mg (15/92) plus lifestyle modifications for 108 weeks. Percent weight loss in the
      intent-to-treat population using multiple imputation (ITT-MI), annualized
      incidence rate of progression to type 2 diabetes, and changes in glycemia, lipid
      parameters, blood pressure, and waist circumference were evaluated. RESULTS At
      baseline, 475 subjects met the criteria for prediabetes and/or MetS. After 108
      weeks, subjects with prediabetes and/or MetS in the placebo, 7.5/46, and 15/92
      groups experienced mean percent weight loss of 2.5, 10.9, and 12.1%, respectively
      (ITT-MI; P < 0.0001 vs. placebo), associated with reductions of 70.5 and 78.7% in
      the annualized incidence rate of type 2 diabetes for those receiving 7.5/46 and
      15/92, respectively (ITT, P < 0.05), versus placebo. The ability of PHEN/TPM ER
      to prevent diabetes was related to degree of weight lost and was accompanied by
      significant improvements in cardiometabolic parameters. PHEN/TPM ER was well
      tolerated by this subgroup over 2 years. CONCLUSIONS PHEN/TPM ER plus lifestyle
      modification produced significant weight loss and markedly reduced progression to
      type 2 diabetes in overweight/obese patients with prediabetes and/or MetS,
      accompanied by improvements in multiple cardiometabolic disease risk factors. 

PMID- 24103902
TI  - Real-time continuous glucose monitoring significantly reduces severe hypoglycemia
      in hypoglycemia-unaware patients with type 1 diabetes.
AB  - OBJECTIVE: To evaluate the effect of continuous glucose monitoring (CGM) on the
      frequency of severe hypoglycemia (SH) in patients with established hypoglycemia
      unawareness. RESEARCH DESIGN AND METHODS: We conducted a retrospective audit of
      35 patients with type 1 diabetes and problematic hypoglycemia unawareness,
      despite optimized medical therapy (continuous subcutaneous insulin
      infusion/multiple daily insulin injections), who used CGM for >1 year. RESULTS:
      Over a 1-year follow-up period, the median rates of SH were reduced from 4.0
      (interquartile range [IQR] 0.75-7.25) episodes/patient-year to 0.0 (0.0-1.25)
      episodes/patient-year (P < 0.001), and the mean (+/-SD) rates were reduced from
      8.1 +/- 13 to 0.6 +/- 1.2 episodes/year (P = 0.005). HbA1c was reduced from 8.1
      +/- 1.2% to 7.6 +/- 1.0% over the year (P = 0.005). The mean Gold score, measured
      in 19 patients, did not change: 5.1 +/- 1.5 vs. 5.2 +/- 1.9 (P = 0.67).
      CONCLUSIONS: In a specialist experienced insulin pump center, in carefully
      selected patients, CGM reduced SH while improving HbA1c but failed to restore
      hypoglycemia awareness.

PMID- 24103903
TI  - Therapeutic cell encapsulation techniques and applications in diabetes.
AB  - The encapsulation of therapeutic cells permits the implantation of allogeneic and
      xenogeneic cells for the regulation of certain physiological processes damaged by
      the death or senescence of host tissues. The encapsulation of pancreatic cells
      for the treatment of diabetes is emphasized; however, many of the techniques are
      applicable to a wide array of mammalian cell applications. The summary of both
      established and novel encapsulation techniques, clinical trials, and commercial
      product developments highlights the metered but steady pace of therapeutic cell
      encapsulation towards implementation. 

PMID- 24103904
TI  - Partial neural protection with prophylactic low-dose melatonin after asphyxia in
      preterm fetal sheep.
AB  - Melatonin is a naturally occurring indolamine with mild antioxidant properties
      that is neuroprotective in perinatal animals. There is limited information on its
      effects on preterm brain injury. In this study, 23 chronically instrumented fetal
      sheep received 25 minutes of complete umbilical cord occlusion at 101 to 104 days
      gestation (term is 147 days). Melatonin was administered to the ewe 15 minutes
      before occlusion (0.1 mg/kg bolus followed by 0.1 mg/kg per hour for 6 hours,
      n=8), or the equivalent volume of vehicle (2% ethanol, n=7), or saline (n=8), or
      maternal saline plus sham occlusion (n=8). Sheep were killed after 7 days
      recovery in utero. Fetal blood pressure, heart rate, nuchal activity, and
      temperature were similar between groups. Vehicle infusion was associated with
      improved neuronal survival in the caudate nucleus, but greater neuronal loss in
      the regions of the hippocampus, with reduced proliferation and increased ameboid
      microglia in the white matter (P<0.05). Maternal melatonin infusion was
      associated with faster recovery of fetal EEG, prolonged reduction in carotid
      blood flow, similar neuronal survival to vehicle, improved numbers of mature
      oligodendrocytes, and reduced microglial activation in the white matter (P<0.05).
      Prophylactic maternal melatonin treatment is partially protective but its effects
      may be partly confounded by ethanol used to dissolve melatonin. 

PMID- 24103905
TI  - Angiographic circulation time and cerebral blood flow during balloon test
      occlusion of the internal carotid artery.
AB  - Angiography-based balloon test occlusion (BTO) has been empirically used to
      predict tolerance to permanent carotid artery occlusion. We tested the hypothesis
      that the laterality of the hemispheric circulation time (HCT) of the contrast
      medium at cerebral angiography would reflect bilateral asymmetry of the cerebral
      blood flow (CBF) during BTO. Thirty-one consecutive patients who underwent BTO of
      the internal carotid artery were retrospectively analyzed. HCT was defined as the
      interval between the time-to-peak in the middle cerebral artery and the cortical
      veins calculated using time-density curve. The difference in HCT between the
      occluded and nonoccluded side was calculated at the carotid or dominant vertebral
      angiograms obtained during BTO. We estimated the correlation between the
      difference in HCT and bilateral asymmetry of the CBF, which was quantitatively
      determined by single-photon emission computed tomography. The HCT was 5.3+/-1.5
      seconds and regional CBF was 41.3+/-11.3 mL/100 g per minute in the occluded
      side, compared with 3.6+/-0.9 seconds and 48.4+/-14.9 mL/100 g per minute in the
      nonoccluded side, respectively. The difference in HCT was strongly correlated
      with the asymmetry ratio of the CBF (r(2)=0.89, P<0.0001). Angiographically based
      measurement of the cerebral circulation time can provide valuable information
      concerning cerebral hemodynamics. 

PMID- 24103906
TI  - Comparison of PrestoBlue and MTT assays of cellular viability in the assessment
      of anti-proliferative effects of plant extracts on human endothelial cells.
AB  - INTRODUCTION: PrestoBlue (PB) is a new, simple and extremely fast live assay to
      monitor cell viability and cytotoxicity. Herein, we compared two in vitro
      cytotoxicity assays, new (PB) and classic (MTT), in the assessment of viability
      of human umbilical vein endothelial cells (HUVECs) in the presence of selected
      plant extracts. METHODS: The anti-proliferative effects of two extracts from
      medicinal plants, i.e., walnut husk extract and spent hop extract, used at the
      concentration range of 1-200 MUg/ml of gallic acid equivalent, were compared with
      the effects recorded for resveratrol--a natural polyphenolic compound. Reduction
      of dyes by endothelial cells was determined colorimetrically (MTT and PB) and
      fluorometrically (PB). RESULTS: At higher concentrations, all tested compounds
      caused significant loss of cell viability. Regardless of plant compound, the PB
      assay, when measured colorimetrically, produced higher EC50 values compared to
      other modes of measurement, however, the statistically significant differences in
      EC50 values among the assays were revealed only for spent hop extract.
      Conversely, the EC50 values for each plant compound obtained in MTT (colorimetric
      assay) and PB (fluorometric assay) were similar. According to EC50 values, the
      cytotoxicity of plant compounds ranked as follows: spent hop
      extract>resveratrol>walnut husk extract. Furthermore, the MTT assay showed
      overall lower inter-assay variability and higher signal-to-noise ratio compared
      to PB assay. DISCUSSION: In conclusion, we recommend fluorometric PrestoBlue
      assay for cytotoxicity assessment in human endothelial cells. Due to substantial
      differences in EC50 values and S/N ratios between spectrophotometric PB and MTT
      or fluorometric PB assays, colorimetric quantification of HUVECs' viability with
      the use of PB reagent should be avoided.

PMID- 24103907
TI  - Do gender and age moderate the symptom structure of PTSD? Findings from a
      national clinical sample of children and adolescents.
AB  - A substantial body of evidence documents that the frequency and intensity of
      posttraumatic stress disorder (PTSD) symptoms are linked to such demographic
      variables as female sex (e.g., Kaplow et al., 2005) and age (e.g., Meiser-Stedman
      et al., 2008). Considerably less is known about relations between biological sex
      and age with PTSD's latent factor structure. This study systematically examined
      the roles that sex and age may play as candidate moderators of the full range of
      factor structure parameters of an empirically supported five-factor PTSD model
      (Elhai et al., 2011). The sample included 6591 trauma-exposed children and
      adolescents selected from the National Child Traumatic Stress Network's Core Data
      Set. Confirmatory factor analysis using invariance testing (Gregorich, 2006) and
      comparative fit index difference values (Cheung and Rensvold, 2002) reflected a
      mixed pattern of test item intercepts across age groups. The adolescent subsample
      produced lower residual error variances, reflecting less measurement error than
      the child subsample. Sex did not show a robust moderating effect. We conclude by
      discussing implications for clinical assessment, theory building, and future
      research. 

PMID- 24103908
TI  - Anti-brain autoantibodies in the serum of schizophrenic patients: a case-control
      study.
AB  - Schizophrenia is considered a neurodevelopmental disorder with a multifactorial
      pathogenesis where autoimmune factors may play a significant role. The aim of
      this study was to verify the presence of anti-brain autoantibodies in the serum
      of schizophrenic patients compared to healthy controls. Autoantibodies against
      brain were detected by the immunofluorescence method, utilizing sections of rat
      hippocampus and hypothalamus and of monkey cerebellum. Three different
      fluorescence patterns were observed, staining the nucleus-cytoplasm of neurons,
      the neuroendothelial of blood vessel and the neurofilaments. Search for other
      organ-specific and non organ-specific autoantibodies was performed in all sera by
      indirect immunofluorescence method, enzyme linked immunosorbent assay and
      chemiluminescence immunoassay. Results showed a significant association between
      schizophrenia and anti-brain autoantibodies against the neuroendothelium of blood
      vessel in hypothalamus, hippocampus and cerebellum; a significant nuclear and
      cytoplasmic staining of neurons was assessed only for the hippocampus. No other
      significant association was found, except between schizophrenia and anti-nuclear
      autoantibodies on HEp-2 cells. In conclusion, these results support the
      hypothesis of a significant association between schizophrenia and circulating
      anti-brain autoantibodies, suggesting a diffuse reactivity against the
      neuroendothelium of blood vessel and highlighting a nuclear and cytoplasmic
      staining of the neurons of hippocampus. 

PMID- 24103909
TI  - Superior mentalizing abilities of female patients with schizophrenia.
AB  - Mentalizing abilities are severely disrupted in patients with schizophrenia, but
      gender-related differences in this domain are virtually unexplored. Given the
      importance of these abilities in understanding psychopathology, social
      functioning and outcome, this study aimed to examine the mentalizing abilities of
      male and female patients with schizophrenia. The cognitive and affective
      mentalizing abilities of self and other of clinically stable male and female
      patients with schizophrenia were analyzed using the abbreviated version of the
      Metacognitive Assessment Scale (MAS-A). Compared to their male counterparts, the
      female patients demonstrated superior overall mentalizing abilities. This
      advantage was also evident when mentalizing about the Self or the Other. When
      examining cognitive versus affective mentalizing, women were significantly better
      in their ability to attribute and understand the affective mental states of
      others. These differences were unrelated to intelligence or psychopathology. The
      superior mentalizing abilities of female patients extend gender-related
      differences in schizophrenia to include social cognition. This suggests that our
      current knowledge of socio-cognitive abilities in schizophrenia is generalizable
      to male but not to female patients. The findings also provide important insights
      to understanding how etiological differences affect social cognition. Awareness
      to such differences has important implications for diagnosis and clinical
      treatment. 

PMID- 24103910
TI  - A clinical and demographic comparison between a forensic and a general sample of
      female patients with schizophrenia.
AB  - Diagnoses of psychiatric diseases do not include criminal behavior. In
      schizophrenia, a non-negligible subgroup is incarcerated for capital and other
      crimes. Most studies that compared offender and non-offender patients with
      schizophrenia have only focused on male patients. With this study, we compared
      demographic and disease-related characteristics between 35 female incarcerated
      forensic patients (fSZ) and 35 female inpatients with schizophrenia (SZ). Basic
      clinical documentation and basic forensic clinical documentation revealed
      significant clinical and demographic differences between the two groups. Compared
      to SZ, fSZ were more severely clinically impaired, showing higher rates of
      comorbid alcohol and substance disorder, more suicide attempts, had more previous
      hospitalizations, and were younger at disease onset. Regarding demographic
      variables, fSZ showed a higher rate of unemployment and homelessness and had to
      rely more often on housing and legal guardianships compared to SZ. These results
      suggest that female forensic patients with schizophrenia are more severely
      affected by clinical and non-clinical variables requiring an adapted intervention
      program. These results may also indicate two developmental trajectories for
      criminal and non-criminal schizophrenia in females. 

PMID- 24103911
TI  - Mutations in B4GALNT1 (GM2 synthase) underlie a new disorder of ganglioside
      biosynthesis.
AB  - Glycosphingolipids are ubiquitous constituents of eukaryotic plasma membranes,
      and their sialylated derivatives, gangliosides, are the major class of
      glycoconjugates expressed by neurons. Deficiencies in their catabolic pathways
      give rise to a large and well-studied group of inherited disorders, the lysosomal
      storage diseases. Although many glycosphingolipid catabolic defects have been
      defined, only one proven inherited disease arising from a defect in ganglioside
      biosynthesis is known. This disease, because of defects in the first step of
      ganglioside biosynthesis (GM3 synthase), results in a severe epileptic disorder
      found at high frequency amongst the Old Order Amish. Here we investigated an
      unusual neurodegenerative phenotype, most commonly classified as a complex form
      of hereditary spastic paraplegia, present in families from Kuwait, Italy and the
      Old Order Amish. Our genetic studies identified mutations in B4GALNT1 (GM2
      synthase), encoding the enzyme that catalyzes the second step in complex
      ganglioside biosynthesis, as the cause of this neurodegenerative phenotype.
      Biochemical profiling of glycosphingolipid biosynthesis confirmed a lack of GM2
      in affected subjects in association with a predictable increase in levels of its
      precursor, GM3, a finding that will greatly facilitate diagnosis of this
      condition. With the description of two neurological human diseases involving
      defects in two sequentially acting enzymes in ganglioside biosynthesis, there is
      the real possibility that a previously unidentified family of ganglioside
      deficiency diseases exist. The study of patients and animal models of these
      disorders will pave the way for a greater understanding of the role gangliosides
      play in neuronal structure and function and provide insights into the development
      of effective treatment therapies. 

PMID- 24103912
TI  - Use of quadrupedal step training to re-engage spinal interneuronal networks and
      improve locomotor function after spinal cord injury.
AB  - Can lower limb motor function be improved after a spinal cord lesion by re
      engaging functional activity of the upper limbs? We addressed this issue by
      training the forelimbs in conjunction with the hindlimbs after a thoracic spinal
      cord hemisection in adult rats. The spinal circuitries were more excitable, and
      behavioural and electrophysiological analyses showed improved hindlimb function
      when the forelimbs were engaged simultaneously with the hindlimbs during
      treadmill step-training as opposed to training only the hindlimbs. Neuronal
      retrograde labelling demonstrated a greater number of propriospinal labelled
      neurons above and below the thoracic lesion site in quadrupedally versus
      bipedally trained rats. The results provide strong evidence that actively
      engaging the forelimbs improves hindlimb function and that one likely mechanism
      underlying these effects is the reorganization and re-engagement of rostrocaudal
      spinal interneuronal networks. For the first time, we provide evidence that the
      spinal interneuronal networks linking the forelimbs and hindlimbs are amenable to
      a rehabilitation training paradigm. Identification of this phenomenon provides a
      strong rationale for proceeding toward preclinical studies for determining
      whether training paradigms involving upper arm training in concert with lower
      extremity training can enhance locomotor recovery after neurological damage. 

PMID- 24103913
TI  - Restoration of sensorimotor functions after spinal cord injury.
AB  - The purpose of this review is to discuss the achievements and perspectives
      regarding rehabilitation of sensorimotor functions after spinal cord injury. In
      the first part we discuss clinical approaches based on neuroplasticity, a term
      referring to all adaptive and maladaptive changes within the sensorimotor systems
      triggered by a spinal cord injury. Neuroplasticity can be facilitated through the
      training of movements with assistance as needed, and/or by electrical stimulation
      techniques. The success of such training in individuals with incomplete spinal
      cord injury critically depends on the presence of physiological proprioceptive
      input to the spinal cord leading to meaningful muscle activations during movement
      performances. The addition of rehabilitation technology, such as robotic devices
      allows for longer training times and provision of feedback information regarding
      changes in movement performance. Nevertheless, the improvement of function by
      such approaches for rehabilitation is limited. In the second part, we discuss
      preclinical approaches to restore function by compensating for the loss of
      descending input to spinal networks following complete spinal cord injury. This
      can be achieved with stimulation of spinal networks or approaches to restore
      their descending input. Electrical and pharmacological stimulation of spinal
      neural networks is still in an experimental stage; and despite promising repair
      studies in animal models, translations to humans up to now have not been
      convincing. It is likely that combinations of techniques targeting the promotion
      of axonal regeneration and meaningful plasticity are necessary to advance the
      restoration of function. In the future, refinement of animal studies may
      contribute to greater translational success. 

PMID- 24103915
TI  - Improving breast cancer detection using ultrasonography in asymptomatic women
      with non-fatty breast density.
AB  - BACKGROUND: Mammography (MX) is a reliable modality for detection of breast
      cancer in asymptomatic women. Use of additional whole breast ultrasonography (US)
      for breast cancer screening is widely recognized, in particular in women with
      dense breast parenchyma. PURPOSE: To determine the subgroup of women, according
      to breast density and age, who receive most benefit from US following MX for
      detection of breast cancer in an asymptomatic condition. MATERIAL AND METHODS:
      The study was conducted in asymptomatic women who had non-fatty breast parenchyma
      using MX and US during January 2006 and December 2007. Mammographic breast
      density was classified as recommended by ACR BI-RADS lexicon. Non-fatty breast
      referred to D2, D3, and D4. US was performed by the same radiologists who
      interpreted MX with a handheld machine during the same visit. Data on
      demographics, cancer detection rate (CDR), and incremental cancer detection rate
      (ICDR) were analyzed using 95% confident interval (CI). RESULTS: Of 14,483 breast
      cancer screenings in women who had non-fatty breast density, 115 cancers were
      documented. The mean age of cancer patients was 49.6 years. Of 115 cancers, 105
      were evidenced on images (31 with MX alone, 19 with US alone, and 55 with both MX
      and US). Overall CDR was 7.9 per 1000 examination (95% CI, 6.5-9.5). CDR for MX
      only (MX-CDR) was 6.5 per 1000 examinations (95% CI, 5.2-7.9). Additional US
      could significantly improve CDR (P < 0.001; 95% CI, 0.9-2.2); US-ICDR was 1.4 per
      1000 examinations. According to age group, the group of 40-59 years had
      statistically significant improvement of ICDR (P < 0.001). The ICDR was highest
      in D4 breast density (D4) (US-ICDR = 2.5 per 1000 examinations). CONCLUSION: Use
      of US adjunct to MX for detection of breast cancer in asymptomatic non-fatty,
      average-risk women for detection of breast cancer is a promising diagnostic
      procedure. A significant benefit was documented, in particular, in women aged 40
      59 years old, and in women with D4 breast density.

PMID- 24103916
TI  - Imaging characteristics of primary intracranial teratoma.
AB  - BACKGROUND: Primary intracranial teratomas are rare intracranial neoplasms, and
      are subdivided into mature, immature, and those with malignant transformation. To
      date, only a few studies of teratoma imaging have been reported. PURPOSE: To
      describe and characterize the magnetic resonance imaging (MRI) findings in a
      series of 18 patients (16 men/boys and 2 women/girls; mean age, 14.5 years) with
      pathologically proven teratomas. MATERIAL AND METHODS: Findings from medical
      records and imaging examinations in 18 patients with pathologically confirmed
      intracranial teratomas from 2001 to 2011 were retrospectively reviewed at our two
      institutions. Two radiologists evaluated the lesion location, shape, size,
      number, edge, homogeneous or heterogeneous appearance, attenuation, signal
      intensity, and degree of enhancement. RESULTS: All tumors were located within the
      pineal (n = 13), parasellar (n = 2), or suprasellar (n = 3) regions. The lesions
      appeared of mixed intensity on MRI, reflecting the histologic heterogeneity,
      including fibrosis, fatty tissue, calcification, cysts, and keratinocytes. In
      mature teratomas (n = 9), seven of nine tumors showed non-enhanced
      multilocularity or heterogeneous enhancement of the cyst wall on contrast
      enhanced T1-weighted (T1W) images. Two of nine tumors showed moderate,
      heterogeneous enhancement in the solid portion of the lesion; whereas in immature
      (n = 7) or malignant transformation (n = 2) teratomas, heterogeneous, ring-like,
      intratumoral patchy enhancement was noted on T1W images with contrast.
      CONCLUSION: Primary intracranial teratomas are usually localized in the pineal
      and the suprasellar regions, and often present an ovoid or lobulated mass with or
      without multilocularity on MRI. Marked enhancement of the solid portion or the
      thick wall of the tumor was the key feature for distinguishing mature teratoma
      and malignant teratoma.

PMID- 24103914
TI  - Understanding nuclear receptor form and function using structural biology.
AB  - Nuclear receptors (NRs) are a major transcription factor family whose members
      selectively bind small-molecule lipophilic ligands and transduce those signals
      into specific changes in gene programs. For over two decades, structural biology
      efforts were focused exclusively on the individual ligand-binding domains (LBDs)
      or DNA-binding domains of NRs. These analyses revealed the basis for both ligand
      and DNA binding and also revealed receptor conformations representing both the
      activated and repressed states. Additionally, crystallographic studies explained
      how NR LBD surfaces recognize discrete portions of transcriptional coregulators.
      The many structural snapshots of LBDs have also guided the development of
      synthetic ligands with therapeutic potential. Yet, the exclusive structural focus
      on isolated NR domains has made it difficult to conceptualize how all the NR
      polypeptide segments are coordinated physically and functionally in the context
      of receptor quaternary architectures. Newly emerged crystal structures of the
      peroxisome proliferator-activated receptor-gamma-retinoid X receptor alpha
      (PPARgamma-RXRalpha) heterodimer and hepatocyte nuclear factor (HNF)-4alpha
      homodimer have recently revealed the higher order organizations of these receptor
      complexes on DNA, as well as the complexity and uniqueness of their domain-domain
      interfaces. These emerging structural advances promise to better explain how
      signals in one domain can be allosterically transmitted to distal receptor
      domains, also providing much better frameworks for guiding future drug discovery
      efforts. 

PMID- 24103917
TI  - CT angiography for pulmonary embolism detection: the effect of breathing on
      pulmonary artery enhancement using a 64-row detector system.
AB  - BACKGROUND: Computed tomography pulmonary angiography (CTPA) is used most often
      in routine clinical practice for the assessment of a suspected pulmonary
      embolism. The diagnostic accuracy relies on sufficient contrast enhancement.
      PURPOSE: To evaluate whether image acquisition during shallow breathing can
      improve the image quality in patients with insufficient contrast enhancement
      during breath-hold examinations. MATERIAL AND METHODS: A total of 2786 CT
      pulmonary angiographies, acquired on a 64-row CT during deep-inspiration breath
      hold, were reviewed. Twenty-four examinations were considered non-diagnostic due
      to poor contrast enhancement in the pulmonary arteries (PA), although they showed
      preserved vascular enhancement of the superior vena cava (SVC) and the ascending
      aorta (AO). Eleven flawed CTPA examinations, including severe breathing artifacts
      and incorrect triggering were excluded. In 13 of the remaining patients, the
      examination was repeated during shallow breathing. Vascular contrast enhancement
      was compared between both scans by measuring the relative enhancement within the
      SVC, the main PA, and the AO. Image quality was scored by two, clinically
      experienced radiologists. The values are given as median and [25th;75th]
      quartile. RESULTS: There was a significant difference in the CT values for the PA
      between the repeated scans (P = 0.0002, Wilcoxon test), and with the CTPA in deep
      inspiration showing a median enhancement of 97 HU (59-173), compared with 303 HU
      (239-385) in the CTPA acquired during free breathing. The differences for both
      the AO (P = 0.54) and the SVC (P = 0.78) were not significant. Scoring for the
      attenuation quality rose significantly (P = 0.0002) and no severe motion
      artifacts were detected on either scans. CONCLUSION: If there is insufficient
      pulmonary artery enhancement during CTPA, attenuation of the pulmonary arteries
      can be improved by acquisition during shallow breathing and is without
      significant loss of the overall diagnostic image quality.

PMID- 24103918
TI  - Serum concentrations of anti-thyroid peroxidase and anti-thyroglobulin antibodies
      in children and adolescents without apparent thyroid disorders.
AB  - OBJECTIVE: The age-dependent prevalence and clinical relevance of anti-thyroid
      peroxidase (TPOAb) and anti-thyroglobulin (TGAb) antibodies in children and
      adolescents without thyroid diseases are unknown. The aim of this study was to
      measure the concentration of these thyroid autoantibodies in a large cohort of
      hospitalized and out-patient subjects. Additionally, we investigated the
      correlation of TPOAb and TGAb with thyroid parameters as well as with putative
      confounding parameters such as standard deviation scores (SDS) of height, BMI-SDS
      and CRP. METHODS: Serum samples from 841 patients with non-thyroid related
      diseases between 1 day post partum and 20 years of age were used in a cross
      sectional study. TPOAb, TGAb, thyroid parameters (TSH, fT3, fT4 and
      thyroglobulin) and CRP were measured by the Modular System (Roche, Mannheim).
      RESULTS: The values of TPOAb and TGAb showed an age-dependent maximum of antibody
      frequency for both genders during the first year of life with concentrations of
      163 IU/mL and 161 IU/mL in the 95th percentile. In girls, a second maximum was
      observed during puberty with concentrations of 82 IU/mL TPOAb and 582 IU/mL TGAb
      in the 95th percentile. Both antibodies correlated significantly (p<0.05) with
      each other, with fT3, fT4, BMI-SDS (only TPOAb) and CRP and TSH (only TGAb).
      CONCLUSION: The prevalence of TPOAb and TGAb was shown to be age-dependent with
      increased values in the first year of life and during puberty. The increased
      "physiological" concentrations of TPOAb and TGAb have to be considered when used
      as diagnostic indicators of autoimmune thyroid disease in a paediatric
      population.

PMID- 24103919
TI  - [Health situation and issues in the Seychelles in 2012].
AB  - Off the coast of Kenya, the Seychelles, home to 87,400 inhabitants mostly of
      African origin, have largely completed their demographic and epidemiologic
      transitions. Major investments in infrastructure and social services have
      fostered steady economic growth. Health care and education are free. The
      predominance of chronic non-communicable diseases and rapid aging of the
      population nonetheless present significant challenges for public health and the
      health system. Like the other small island states in the region, the Seychelles
      continue to be threatened by arbovirus outbreaks. Health indicators are good, but
      the geographic isolation, the small and aging population, and limited resources
      make a major challenge maintaining and sustaining an effective workforce of
      health professionals, a constantly evolving technical platform, and increasing
      amount of medications particularly in view of the increasing burden of chronic
      diseases.

PMID- 24103920
TI  - OsKAT2 is the prevailing functional inward rectifier potassium channels in rice
      guard cell.
AB  - AtKAT1 plays roles as a major channel to uptake K(+) in guard cell when stomata
      open in dicot model plant Arabidopsis. In a recent publication, we isolated 3 KAT
      like potassium channels in rice. We expressed them in CHO cell to identify
      electrophysiological characteristics of the channels. OsKAT2 showed much bigger
      inwardly rectifying potassium channel activities among them. The histochemical X
      glu staining of transgenic rice leaf blades expressing beta-glucuronidase fused
      with OsKAT2 promoter showed that the OsKAT2 is dominantly expressed in rice guard
      cell. These findings indicate that OsKAT2 may be a functional ortholog of AtKAT1
      in rice. Thus this gene will be the prime target for engineering the guard cell
      movement to improve drought tolerance in monocot plants, including most major
      crops.

PMID- 24103921
TI  - Patterns of growth in ambulatory males with Duchenne muscular dystrophy.
AB  - OBJECTIVE: To provide weight-for-age, height-for-age, and body mass index-for-age
      growth reference standards for ambulatory, steroid-naive males, ages 2-12 years,
      with Duchenne muscular dystrophy (DMD) and to compare these growth curves to the
      2000 Centers for Disease Control and Prevention growth charts for boys, which
      serve as references of physical size and growth for the general male pediatric
      population in the US. STUDY DESIGN: Through a multi-state population-based
      surveillance of individuals with muscular dystrophy, a total of 1877 weight and
      1544 height measurements ascertained during 1985-2010 from 513 males with DMD
      were obtained retrospectively from medical record review. Cases were classified
      as DMD if loss of ambulation occurred before the 12th birthday or, if younger
      than 12 years and still ambulating, the earliest symptoms of dystrophinopathy
      occurred before the 6th birthday. Each growth chart was constructed using 5
      percentiles: 10th, 25th, 50th, 75th, and 90th. Smoothing procedures were applied
      in 2 stages to the irregular plots of the empirical percentile values. RESULTS: A
      set of growth curves, derived from a large cohort of male youth with DMD, are
      presented. These curves demonstrate that DMD males are shorter and tend to the
      extremes of weight and body mass index compared with the general male pediatric
      population in the US. CONCLUSION: Charts representing the pattern of growth in
      ambulatory, steroid-naive males with DMD can facilitate monitoring of growth and
      early detection of unusual growth patterns. Use of these growth standards also
      will assist in monitoring responses to corticosteroid treatment.

PMID- 24103923
TI  - Orientation dependent wavefront correction system under grazing incidence.
AB  - Making use of the stretching effect of grazing incident laser beam, a novel
      method of wavefront correction was promoted. Without adding any extra beam
      expanding components, aberrations of wavefront could achieve satisfying
      correction by two grazing reflections along orthogonal directions on the
      deformable mirrors. The stretching effect expanded the beam size along grazing
      direction and the orientation dependent varying aberrations were well compensated
      as more actuators took effect in the correction process. Analysis showed that the
      fitting coefficient of all the first 30 order Zernike polynomials could be
      controlled within 5% by this method. 

PMID- 24103924
TI  - Resonant transport of light from planar polymer waveguide into liquid-crystal
      microcavity.
AB  - We demonstrate the resonant transfer of light from a planar waveguide to a
      nematic liquid-crystal microdroplet immersed in water. A wide spectrum of light
      from a supercontinuum laser source is coupled into a high-refractive-index
      polymer waveguide using a prism-film coupler. The waveguide is in contact with a
      water dispersion of droplets from the nematic liquid-crystal 5CB. The evanescent
      field of the light in the waveguide is resonantly coupled to the whispering
      gallery mode resonances, sustained by 5 - 20 MUm-sized nematic liquid-crystal
      droplets, which are in close proximity to the waveguide. The resonant transfer of
      light is tuned by the temperature-induced shifting of the WGM resonances due to
      the temperature dependence of the refractive index of the nematic liquid crystal.
      The measurements are compared to the calculations of the coupled-mode theory.

PMID- 24103922
TI  - The increase of the functional entropy of the human brain with age.
AB  - We use entropy to characterize intrinsic ageing properties of the human brain.
      Analysis of fMRI data from a large dataset of individuals, using resting state
      BOLD signals, demonstrated that a functional entropy associated with brain
      activity increases with age. During an average lifespan, the entropy, which was
      calculated from a population of individuals, increased by approximately 0.1 bits,
      due to correlations in BOLD activity becoming more widely distributed. We
      attribute this to the number of excitatory neurons and the excitatory conductance
      decreasing with age. Incorporating these properties into a computational model
      leads to quantitatively similar results to the fMRI data. Our dataset involved
      males and females and we found significant differences between them. The entropy
      of males at birth was lower than that of females. However, the entropies of the
      two sexes increase at different rates, and intersect at approximately 50 years;
      after this age, males have a larger entropy. 

PMID- 24103925
TI  - Laser-induced fluorescence of uranyl complexes in aqueous solutions: the role of
      diffusion-controlled excited states annihilation.
AB  - We present the analysis of diffusion-controlled annihilation of excited U(VI)
      complexes in aqueous media that leads to appearance of rapid non-exponential
      fluorescence decay. We show that under typical experimental conditions the impact
      of annihilation processes can't be neglected when determining U(VI) complexes
      fluorescence lifetimes: at excitation intensities between 10(6) W/cm(2) and 10(8)
      W/cm(2), the rate of excited states deactivation increases, and then an opposite
      trend is observed. The latter can be interpreted as the consequence of optical
      breakdown in water.

PMID- 24103926
TI  - Performance analysis for IEEE 802.11 distributed coordination function in radio
      over-fiber-based distributed antenna systems.
AB  - In this paper, we analyze the performance of IEEE 802.11 distributed coordination
      function in simulcast radio-over-fiber-based distributed antenna systems (RoF
      DASs) where multiple remote antenna units (RAUs) are connected to one wireless
      local-area network (WLAN) access point (AP) with different-length fiber links. We
      also present an analytical model to evaluate the throughput of the systems in the
      presence of both the inter-RAU hidden-node problem and fiber-length difference
      effect. In the model, the unequal delay induced by different fiber length is
      involved both in the backoff stage and in the calculation of Ts and Tc, which are
      the period of time when the channel is sensed busy due to a successful
      transmission or a collision. The throughput performances of WLAN-RoF-DAS in both
      basic access and request to send/clear to send (RTS/CTS) exchange modes are
      evaluated with the help of the derived model. 

PMID- 24103927
TI  - Shaping of light beams along curves in three dimensions.
AB  - We present a method for efficient and versatile generation of beams whose
      intensity and phase are prescribed along arbitrary 3D curves. It comprises a non
      iterative beam shaping technique that does not require solving inversion problems
      of light propagation. The generated beams have diffraction-limited focusing with
      high intensity and controlled phase gradients useful for applications such as
      laser micro-machining and optical trapping. Its performance and feasibility are
      experimentally demonstrated on several examples including multiple trapping of
      micron-sized particles. 

PMID- 24103928
TI  - Evolution of dissipative solitons in a fiber laser oscillator in the presence of
      strong Raman scattering.
AB  - As recently revealed, chirped dissipative solitons (DSs) generated in a long
      cavity fiber laser are subject to action of stimulated Raman scattering (SRS).
      Here we present theoretical and experimental study of the DS formation and
      evolution in the presence of strong SRS. The results demonstrate that the rising
      noisy Raman pulse (RP) acts not only as an additional channel of the energy
      dissipation destroying DS, but on the contrary can support it that results in
      formation of a complex of the bound DS and RP of comparable energy and duration.
      In the complex, the DS affords amplification of the RP, whereas the RP stabilizes
      the DS via temporal-spectral filtering. Stable 25 nJ SRS-driven chirped DS pulses
      are generated in all-fiber ring laser cavities with lengths of up to 120 m. The
      DS with duration up to 70 ps can be externally dechirped to <300 fs thus
      demonstrating the record compression factor. 

PMID- 24103929
TI  - One-step leapfrog ADI-FDTD method for simulating electromagnetic wave propagation
      in general dispersive media.
AB  - The one-step leapfrog alternating-direction-implicit finite-difference time
      domain (ADI-FDTD) method is reformulated for simulating general electrically
      dispersive media. It models material dispersive properties with equivalent
      polarization currents. These currents are then solved with the auxiliary
      differential equation (ADE) and then incorporated into the one-step leapfrog ADI
      FDTD method. The final equations are presented in the form similar to that of the
      conventional FDTD method but with second-order perturbation. The adapted method
      is then applied to characterize (a) electromagnetic wave propagation in a
      rectangular waveguide loaded with a magnetized plasma slab, (b) transmission
      coefficient of a plane wave normally incident on a monolayer graphene sheet
      biased by a magnetostatic field, and (c) surface plasmon polaritons (SPPs)
      propagation along a monolayer graphene sheet biased by an electrostatic field.
      The numerical results verify the stability, accuracy and computational efficiency
      of the proposed one-step leapfrog ADI-FDTD algorithm in comparison with
      analytical results and the results obtained with the other methods. 

PMID- 24103930
TI  - 3D dynamic holographic display by modulating complex amplitude experimentally.
AB  - Complex amplitude modulation method is presented theoretically and performed
      experimentally for three-dimensional (3D) dynamic holographic display with
      reduced speckle using a single phase-only spatial light modulator. The
      determination of essential factors is discussed based on the basic principle and
      theory. The numerical simulations and optical experiments are performed, where
      the static and animated objects without refinement on the surfaces and without
      random initial phases are reconstructed successfully. The results indicate that
      this method can reduce the speckle in reconstructed images effectively;
      furthermore, it will not cause the internal structure in the reconstructed
      pixels. Since the complex amplitude modulation is based on the principle of phase
      only hologram, it does not need the stringent alignment of pixels. This method
      can be used for high resolution imaging or measurement in various optical areas. 

PMID- 24103931
TI  - Semi-analytical approach for guided mode resonance in high-index-contrast
      photonic crystal slab: TE polarization.
AB  - In high-contrast (HC) photonic crystals (PC) slabs, the high-order coupling is so
      intense that it is indispensable for analyzing the guided mode resonance (GMR)
      effect. In this paper, a semi-analytical approach is proposed for analyzing GMR
      in HC PC slabs with TE-like polarization. The intense high-order coupling is
      included by using a convergent recursive procedure. The reflection of radiative
      waves at high-index-contrast interfaces is also considered by adopting a strict
      Green's function for multi-layer structures. Modal properties of interest like
      band structure, radiation constant, field profile are calculated, agreeing well
      with numerical finite-difference time-domain simulations. This analysis is
      promising for the design and optimization of various HC PC devices. 

PMID- 24103933
TI  - Co-enhancing and -confining the electric and magnetic fields of the broken
      nanoring and the composite nanoring by azimuthally polarized excitation.
AB  - We present a novel broken-nanoring, which can realize strongly localized
      confinement and highly enhancement for both electric and magnetic fields at two
      resonant modes excited by normal incident azimuthally polarized light. Two
      resonant modes of the broken-nanoring are formed by different resonant mechanisms
      as different resonant lengths. The physical model for two resonant modes is also
      proposed to explain the mechanisms of the electromagnetic enhancement. The
      enhancement of the electric and magnetic fields can be further improved by adding
      a nanoring at the outside of the broken-nanoring to form a composite nanoring,
      which can freely tune or easily merge the resonant modes of the solitary broken
      nanoring while keeping larger enhancement of the electric and magnetic fields. 

PMID- 24103932
TI  - High quality factor silica microspheres functionalized with self-assembled
      nanomaterials.
AB  - With extremely low material absorption and exceptional surface smoothness, silica
      based optical resonators can achieve extremely high cavity quality (Q) factors.
      However, the intrinsic material limitations of silica (e.g., lack of second order
      nonlinearity) may limit the potential applications of silica-based high Q
      resonators. Here we report some results in utilizing layer-by-layer self-assembly
      to functionalize silica microspheres with nonlinear and plasmonic nanomaterials
      while maintaining Q factors as high as 10(7). We compare experimentally measured
      Q factors with theoretical estimates, and find good agreement.

PMID- 24103934
TI  - Formation of microcavity polaritons in ZnO nanoparticles.
AB  - We report the formation of microcavity polaritons in a dielectric microcavity
      embedded with solution processed ZnO nanoparticles. Evidence of strong coupling
      between the excitons and cavity photons is demonstrated via anticrossing in the
      dispersion of the polariton states. At low temperatures (<150K), multiple
      polariton states arising due to coupling between different excitonic states and
      the cavity mode is observed. Rabi splitting of ~90 meV is shown to persist even
      at room temperature in the ZnO - dielectric microcavity. 

PMID- 24103935
TI  - Automatic electronic-controlled mode locking self-start in fibre lasers with non
      linear polarisation evolution.
AB  - The present work demonstrates a fibre-laser system with automatic electronic
      controlled triggering of dissipative soliton generation mode. Passive mode
      locking based on the effect of non-linear polarisation evolution has been
      achieved through a polarisation controller containing a single low-voltage liquid
      crystal plate whose optimal wave delay was determined from analysis of inter-mode
      beat spectrum of the output radiation. 

PMID- 24103936
TI  - Electron trajectory selection for high harmonic generation inside a short hollow
      fiber.
AB  - The 19th harmonic beam divergences from a Ti:sapphire laser generated using a gas
      jet and 10-mm-long hollow fibers with bore diameters of 300 and 200 MUm were
      investigated. The beam quality factor M(2) of the harmonic beam generated in a
      300-MUm hollow fiber was found to be better than the gas jet using the phase
      match including the atomic dipole phase induced by the short trajectory. On the
      other hand, a 200-MUm hollow fiber was found to generate a more divergent beam
      with a larger M(2) because of the long trajectory. The electron trajectory
      contributing to high harmonic generation was selected using the phase-matching
      process inside a short hollow fiber.

PMID- 24103937
TI  - Temperature-dependent Sellmeier equations of nonlinear optical crystal
      La(2)CaB(10)O(19).
AB  - The thermal dependence principal refractive indices ofLa(2)CaB(10)O(19) (LCB)
      crystal at wavelengths of 0.254, 0.365, 0.405, 0.480, 0.546, 0.644, 0.852, 1.014,
      and 2.325 MUm were accurately measured by using the vertical incidence method
      within the temperature range from 25 to 170  degrees C. We derived equations of
      thermal refractive index coefficients as a function of wavelength that could be
      used to calculate the principal thermal refractive indices at different
      wavelengths. The temperature-dependent Sellmeier equations were also derived and
      used to calculate the phase-matching angles for the third-harmonic generation of
      LCB crystal at different temperatures. Theoretical and experimental phase
      matching angles for the type I third-harmonic generation of LCB crystal at
      different temperatures were in good agreement.

PMID- 24103938
TI  - A wavelength-preserving photonic integrated regenerator for NRZ and RZ signals.
AB  - This paper presents a novel Indium Phosphide based photonic integrated circuit
      (PIC) for all-optical regeneration of both nonreturn-to-zero (NRZ) and return-to
      zero (RZ) on-off-keying (OOK) signals. The PIC exploits cross gain compression in
      two semiconductor optical amplifiers to simultaneously obtain a wavelength
      preserved and reshaped copy, and a wavelength-converted yet inverted copy of the
      input signal. Regeneration of 10 Gb/s signals on multiple wavelengths is
      demonstrated, showing a Q-factor improvement from 1.5 to 4 for NRZ-OOK signals
      and from 2.3 to 3.6 for RZ-OOK signals, and a BER improvement up to 1.5 decades. 

PMID- 24103939
TI  - Mie scattering from submicron-sized CO2 clusters formed in a supersonic expansion
      of a gas mixture.
AB  - A detailed mathematical model is presented for a submicron-sized cluster
      formation in a binary gas mixture flowing through a three-staged conical nozzle.
      By measuring the angular distribution of light scattered from the clusters, the
      size of CO(2) clusters, produced in a supersonic expansion of the mixture gas of
      CO(2)(30%)/H(2)(70%) or CO(2)(10%)/He(90%), has been evaluated using the Mie
      scattering method. The mean sizes of CO(2) clusters are estimated to be 0.28 +/-
      0.03 MUm for CO(2)/H(2) and 0.26 +/- 0.04 MUm for CO(2)/He, respectively. In
      addition, total gas density profiles in radial direction of the gas jet,
      measuring the phase shift of the light passing through the target by utilizing an
      interferometer, are found to be agreed with the numerical modeling within a
      factor of two. The dryness (= monomer/(monomer + cluster) ratio) in the targets
      is found to support the numerical modeling. The apparatus developed to evaluate
      the cluster-gas targets proved that our mathematical model of cluster formation
      is reliable enough for the binary gas mixture.

PMID- 24103940
TI  - Tuning the transmission lineshape of a photonic crystal slab guided-resonance
      mode by polarization control.
AB  - We demonstrate a system consisting of a two-dimensional photonic crystal slab and
      two polarizers which has a tunable transmission lineshape. The lineshape can be
      tuned from a symmetric Lorentzian to a highly asymmetric Fano lineshape by
      rotating the output polarizer. We use temporal coupled mode theory to explain the
      measurement results. The theory also predicts tunable phase shift and group
      delay. 

PMID- 24103941
TI  - Deep sub-wavelength imaging lithography by a reflective plasmonic slab.
AB  - By utilizing a reflective plasmonic slab, it is demonstrated numerically and
      experimentally in this paper deep sub-wavelength imaging lithography for nano
      characters with about 50 nm line width and dense lines with 32 nm half pitch
      resolution (about 1/12 wavelength). Compared with the control experiment without
      reflective plasmonic slab, resolution and fidelity of imaged resist patterns are
      remarkably improved especially for isolated nano features. Further numerical
      simulations show that near field optical proximity corrections help to improve
      imaging fidelity of two dimensional nano patterns.

PMID- 24103942
TI  - Vectorial optical field generator for the creation of arbitrarily complex fields.
AB  - Generation of vectorial optical fields with complex spatial distribution in the
      cross section is of great interest in areas where exotic optical fields are
      desired, including particle manipulation, optical nanofabrication, beam shaping
      and optical imaging. In this work, a vectorial optical field generator capable of
      creating arbitrarily complex beam cross section is designed, built and tested.
      Based on two reflective phase-only liquid crystal spatial light modulators, this
      generator is capable of controlling all the parameters of the spatial
      distributions of an optical field, including the phase, amplitude and
      polarization (ellipticity and orientation) on a pixel-by-pixel basis. Various
      optical fields containing phase, amplitude and/or polarization modulations are
      successfully generated and tested using Stokes parameter measurement to
      demonstrate the capability and versatility of this optical field generator. 

PMID- 24103943
TI  - Optical properties of solid-core photonic crystal fibers filled with nonlinear
      absorbers.
AB  - A theoretical and experimental investigation of the transmission of solid-core
      photonic crystal fibers (PCFs) filled with nonlinear absorbers shows a sharp
      change in the threshold for optical limiting and in leakage loss as the
      refractive index of the material in the holes approaches that of the glass
      matrix. Theoretical calculations of the mode profiles and leakage loss of the PCF
      are in agreement with experimental results and indicate that the change in
      limiting response is due to the interaction of the evanescent field of the guided
      mode with the nonlinear absorbers in the holes. 

PMID- 24103945
TI  - A new balanced-path heterodyne I/Q-interferometer scheme for low environmental
      noise, high sensitivity phase measurements for both reflection and transmission
      geometry.
AB  - A new heterodyne interferometer scheme which has open accesses to both the
      geometrically balanced probe beam (PB) and reference beam (RB) paths, for which,
      depending on the nature of a specific sensing mechanism, a transmission geometry
      or a reflection geometry can be employed, is presented. We will show that,
      because of a small separation between the short length PB and RB running parallel
      to each other our newly proposed optical arrangement allows high rejection of
      unlocalized environmental perturbations. In fact, the geometrically balanced
      optical arrangement provides 19 dB rejection of any vibrations parallel to the
      direction of beam propagation, which cannot be achieved in a conventional
      interferometer scheme. Applications of this new interferometer scheme are
      discussed. As an example, we will show that our newly proposed interferometer
      scheme can be applied for high sensitivity measurements of concentration
      dependent refractive indexes in various solutions.

PMID- 24103944
TI  - Two-photon lensless endoscope.
AB  - We report a first demonstration of two-photon endoscopic imaging with a lensless
      endoscope. The endoscope probe is a double-clad bundle of single-mode fibers;
      point excitation and scanning is achieved by coherent combining of femtosecond
      light pulses propagating in the single-mode fibers; and back-scattered two-photon
      signal is collected through the multi-mode inner cladding. We demonstrate the two
      photon endoscope on a test sample of rhodamine 6G crystals. 

PMID- 24103946
TI  - Inhomogeneity measurement at oblique incidence by phase measuring
      interferometers.
AB  - The huge power solid-state lasers require large optical materials with high
      quality. The inhomogeneity must be required to be measured. Inhomogeneity
      measurement is often done at normal incidence by interferometer, while the size
      of large blanks is limited to the interferometer aperture. A five-step method to
      measure refractive index inhomogeneity over the interferometer aperture is
      proposed in this paper. The variation of the refractive index inhomogeneity of
      the glass blank is directly calculated using five interferograms measured at
      oblique incidence. The high repeatability of the results is given. The
      reliability of the method is further verified by comparing the same part measured
      at normal incidence. 

PMID- 24103947
TI  - Dielectric back scattering patterns for light trapping in thin-film Si solar
      cells.
AB  - We experimentally compare the light trapping efficiency of dielectric and
      metallic backscattering patterns in thin-film a-Si:H solar cells. We compare
      devices with randomly patterned Ag back contacts that are covered with either
      flat or patterned aluminum-doped ZnO (AZO) buffer layers and find the
      nanostructure at the AZO/a-Si:H interface is key to achieve efficient light
      trapping. Simulations show that purely dielectric scattering patterns with flat
      Ag and a patterned AZO/a-Si:H interface can outperform geometries in which the Ag
      is also patterned. The scattering from the dielectric patterns is due to
      geometrical Mie resonances in the AZO nanostructures. The optimized dielectric
      geometries avoid parasitic Ohmic losses due to plasmon resonances in the Ag, and
      open the way to a large number of new light trapping designs based on purely
      dielectric resonant light scattering. 

PMID- 24103948
TI  - Characterization of energy-efficient and colorless ONUs for future TWDM-PONs.
AB  - The Full Services Access Network group has recently selected the time and
      wavelength division multiplexed passive optical network (TWDM-PON) as the base
      technology solution for next-generation PON stage-2 (NG-PON2). Meeting the core
      requirements of NG-PON2 necessitates the following additional features in the
      transceivers of the optical network unit (ONU) that is located at subscriber
      premises: (a) legacy system compliant; (b) wavelength tunable; (c) cost
      efficient; and (d) energy-efficient. To address these features, we investigate
      the properties of short-cavity vertical-cavity surface-emitting lasers (SC
      VCSELs) for implementation as colorless ONU transmitters in future TWDM-PONs.
      Specifically, we investigate the tunability and transmission performance of the
      SC-VCSEL across the C-minus wavelength band for legacy system compliance. We
      report on error-free transmission across a 800 GHz tuning range with a potential
      aggregate upstream capacity of 80 Gbps over a system reach of 40 km and with a
      split ratio of 1:128 per wavelength channel. Results were achieved without
      dispersion compensation and electronic equalization. We also evaluate the energy
      efficiency of the SC-VCSEL in active, doze, and sleep mode. When in active mode,
      the SC-VCSEL transmitter block consumes 91.7% less power than a distributed
      feedback (DFB) laser transmitter block. When transitioning between doze and
      active modes, the transmitter block has a short settling time of only 205 ns,
      thus increasing the power-saving duration and consequently reducing the overall
      power consumption of the ONU. Through numerical analysis, evaluation of the
      energy-savings of the SC-VCSEL ONU over the DFB ONU under various modes of
      operation, demonstrates up to 84% of energy-savings. The capacity, tuning range,
      split ratio, system reach, and energy-savings arising from SC-VCSEL ONU
      implementation as reported in this work, exceed the minimum requirements of NG
      PON2 for future TWDM-PON deployments. 

PMID- 24103949
TI  - Efficient transition between photonic and plasmonic guided modes at abrupt
      junction of MIM plasmonic waveguide.
AB  - We propose a novel metal-insulator-metal (MIM) waveguide mode transition scheme
      by the use of the abrupt junction of MIM plasmonic waveguide. Power coupling
      between anti-symmetric plasmonic mode and fundamental photonic mode can be easily
      done by reflection at the waveguide junction with an oblique MIM mode incidence
      due to the field intersection between those modes. With numerical simulation we
      find that mode conversion efficiency can be obtained up to 60% for single
      junction geometry, and it can be further increased up to 82% with the suppression
      of non-transited mode by adapting Bragg grating structure composed of periodical
      arranges of MIM junctions. 

PMID- 24103950
TI  - Trapping mid-infrared rays in a lossy film with the Berreman mode, epsilon near
      zero mode, and magnetic polaritons.
AB  - Triple mechanisms were employed to trap mid-infrared (mid-IR) rays within a semi
      transparent SiO(2) film sandwiched between gold gratings and a gold substrate.
      Dimensions of four absorbers were explicitly determined using an LC (inductor
      capacitor) circuit model considering the role transition of SiO(2) film. The film
      behaves as a capacitance and an inductance when the real part of relative
      electric permittivity for SiO(2) is positive and negative, respectively. At the
      normal incidence of transverse magnetic waves, every absorptance spectrum of
      absorbers showed a peak at wavelength lambda = 10 MUm due to the first mode
      excitation of magnetic polaritons (MP). At oblique incidence, the Berreman mode
      led to another peak at lambda = 8 MUm while its bandwidth was expanded with
      epsilon near zero mode excited by diffracted waves. The full-width-at-half
      maximum of both peaks exceeded 0.6 MUm thanks to the SiO(2) loss. Other minor
      absorptance peaks in the mid-IR were caused by variants of the same MP mode.

PMID- 24103951
TI  - Polarization-dependent photon switch in a one-dimensional coupled-resonator
      waveguide.
AB  - Polarization-dependent photon switch is one of the most important ingredients in
      building future large-scale all-optical quantum network. We present a scheme for
      a single-photon switch in a one-dimensional coupled-resonator waveguide, where
      N(a) Lambda-type three-level atoms are individually embedded in each of the
      resonator. By tuning the interaction between atom and field, we show that an
      initial incident photon with a certain polarization can be transformed into its
      orthogonal polarization state. Finally, we use the fidelity as a figure of merit
      and numerically evaluate the performance of our photon switch scheme in varieties
      of system parameters, such as number of atoms, energy detuning and dipole
      couplings.

PMID- 24103952
TI  - 1.95 MUm kHz-linewidth single-frequency fiber laser using self-developed heavily
      Tm3+-doped germanate glass fiber.
AB  - We demonstrated a kHz-linewidth single-frequency laser at 1.95 MUm using the self
      developed heavily Tm(3+)-doped single-mode germanate glass fiber with the net
      gain coefficient of 2.3 dB per centimeter. The maximum output power of the stable
      single longitudinal mode continuous wave laser is over 200 mW. The slope
      efficiency measured versus the absorbed pump power is 34.8%, the signal-to-noise
      ratio is higher than 68 dB and laser linewidth is less than 7 kHz. A wavelength
      tuning from 1949.55 to 1951.23 nm was also demonstrated based on changing the
      tension on the fiber Bragg grating outside the cavity.

PMID- 24103953
TI  - Deterministic signal associated with a random field.
AB  - Stochastic fields do not generally possess a Fourier transform. This makes the
      second-order statistics calculation very difficult, as it requires solving a
      fourth-order stochastic wave equation. This problem was alleviated by Wolf who
      introduced the coherent mode decomposition and, as a result, space-frequency
      statistics propagation of wide-sense stationary fields. In this paper we show
      that if, in addition to wide-sense stationarity, the fields are also wide-sense
      statistically homogeneous, then monochromatic plane waves can be used as an
      eigenfunction basis for the cross spectral density. Furthermore, the eigenvalue
      associated with a plane wave, exp[i(k . r-omegat)], is given by the
      spatiotemporal power spectrum evaluated at the frequency (k, omega). We show that
      the second-order statistics of these fields is fully described by the
      spatiotemporal power spectrum, a real, positive function. Thus, the second-order
      statistics can be efficiently propagated in the wavevector-frequency
      representation using a new framework of deterministic signals associated with
      random fields. Analogous to the complex analytic signal representation of a
      field, the deterministic signal is a mathematical construct meant to simplify
      calculations. Specifically, the deterministic signal associated with a random
      field is defined such that it has the identical autocorrelation as the actual
      random field. Calculations for propagating spatial and temporal correlations are
      simplified greatly because one only needs to solve a deterministic wave equation
      of second order. We illustrate the power of the wavevector-frequency
      representation with calculations of spatial coherence in the far zone of an
      incoherent source, as well as coherence effects induced by biological tissues.

PMID- 24103954
TI  - Paper like cholesteric interferential mirror.
AB  - A new type of flexible cholesteric liquid crystal mirror is presented. The simple
      and effective method for the deposition of a cholesteric mixture on a paper
      substrate and the particular design of the device give a homogeneous alignment of
      the cholesteric texture providing mirrors with an intense and uniform light
      reflectance. A desired polarization state for the reflected light, linear or
      circular, can be easily obtained varying the thickness and optical anisotropy of
      the polymer cover film. By using non-azobenzene based photosensitive materials a
      permanent array of RGB mirrors with high reflectivity can be obtained on the same
      device. Paper like reflective mirrors are versatile and they can find
      applications in reflective displays, adaptive optics, UV detectors and
      dosimeters, information recording, medicine and IR converters. 

PMID- 24103955
TI  - Optimizing nanophotonic cavity designs with the gravitational search algorithm.
AB  - Designing photonic crystal cavities with high quality factors and low mode
      volumes is of great importance for maximizing interactions of light and matter in
      metamaterials. Previous work on photonic crystal cavities has revealed dramatic
      improvements in performance by fine-tuning the device design. In L3 cavities,
      slight shifts of the holes on the edge of the cavity have been found to greatly
      increase quality factors without significantly altering the mode volume. Here we
      demonstrate utilizing a nature inspired search algorithm to efficiently explore a
      large parameter space. The results converge upon a new cavity model with a high
      quality factor to mode volume ratio (Q/V = 798,000 (lambda/n)(-3)).

PMID- 24103956
TI  - Hitless wavelength-selective switch with quadruple series-coupled microring
      resonators using multiple-quantum-well waveguides.
AB  - We demonstrate a hitless wavelength-selective switch (WSS) based on InGaAs/InAlAs
      five-layer asymmetric coupled quantum well (FACQW) quadruple series-coupled
      microring resonators. The WSS is driven by the electric-field-induced change in
      refractive index in the FACQW core layer caused by the quantum-confined Stark
      effect (QCSE) for high-speed operation. The WSS with high-mesa waveguides is
      fabricated on a molecular beam epitaxy-grown wafer by dry etching. The fabricated
      WSS consists of four microrings, each with a round-trip length of 350 MUm and
      five directional couplers with shallow grooves. A boxlike spectral response and
      hitless switching with higher extinction ratios than a double series-coupled
      microring resonator are successfully demonstrated. In addition, we propose the
      improvement of switching characteristics by controlling the coupling efficiencies
      at the directional couplers. 

PMID- 24103957
TI  - Investigation of PMD in direct-detection optical OFDM with zero padding.
AB  - We investigate the polarization-mode dispersion (PMD) effect of zero padding OFDM
      (ZP-OFDM) in direct-detection optical orthogonal frequency division multiplexing
      (DDO-OFDM) systems. We first study the conventional equalization method for ZP
      OFDM. Then an equalization method based on sorted QR decomposition is proposed to
      further improve the performance. It is found that the performance improvement of
      ZP-OFDM is due to the frequency domain oversampling (FDO) induced inter-carrier
      interference (ICI). Numerical simulation results show that compared with cyclic
      prefix OFDM (CP-OFDM), ZP-OFDM has a significantly higher tolerance to PMD in DDO
      OFDM systems when the channel spectral nulls occur at certain differential group
      delay (DGD) values. 

PMID- 24103958
TI  - High-efficiency GaN-based light-emitting diodes fabricated with identical Ag
      contact formed on both n- and p-layers.
AB  - The authors report high-efficiency GaN-based light-emitting diodes (LEDs)
      fabricated with identical Ag contact formed on both n- and p-layers. Ag contacts
      thermally annealed at optimized conditions yielded low specific contact
      resistances of 4.5 * 10(-4) and 9.4 * 10(-4) Omegacm(2), and high optical
      reflectivity (at 450 nm) of 88.1 and 85.3% for n- and p-contact, respectively.
      LEDs fabricated with identical Ag contacts formed on both layers showed 31%
      brighter light output power and nearly the same forward voltages as compared to
      reference LEDs. This indicates that Ag contact can be used as a reflective
      electrode for both n- and p-layers, leading to enhanced extraction efficiency and
      fewer process steps.

PMID- 24103959
TI  - An improved refractive index sensor based on genetic optimization of plasmon
      waveguide resonance.
AB  - Plasmon waveguide resonance (PWR) sensors are particularly useful for biosensing
      due to their unique ability to perform sensing with two different polarizations.
      In this paper we report a comprehensive performance comparison between the
      surface plasmon resonance (SPR) sensor and the PWR sensor in terms of the
      sensitivity and the refractive index resolution. Both sensors were optimized
      using a genetic algorithm to acquire their best performance for bulk sensing
      applications. The experimental results show that the PWR sensor has a refractive
      index resolution of 5 * 10(-7) RIU which is 6 times smaller than that of the
      optimized SPR sensor. The TE polarization in the PWR sensor has a resolution of
      1.4 * 10(-6) RIU which is smaller than the SPR sensor. The polarization diversity
      in the PWR sensor is another advantage which can be used to improve the
      measurement reliability.

PMID- 24103960
TI  - Honeycomb-lattice plasmonic absorbers at NIR: anomalous high-order resonance.
AB  - We design, fabricate and characterize a plasmonic honeycomb lattice absorber with
      almost perfect absorption at 1140 nm over a wide incident angle range. This
      absorber also possesses a narrow-band, angle- and polarization-dependent high
      order resonance in the short-wavelength range, with a bandwidth of 19 nm and
      angle sensitivity of 3 nm per degree. The nature of this high-order absorption
      band is analyzed through finite-element simulations. We believe it is due to
      Bragg coupling of the incident light to the backward-propagating surface plasmon
      polariton through the periodic modulation of the structure.Such fine absorption
      bands can find applications in plasmonic sensors and spectrally selective thermal
      emitters. 

PMID- 24103961
TI  - Compact polarizing beam splitter based on a metal-insulator-metal inserted into
      multimode interference coupler.
AB  - We propose and analyze a compact polarizing beam splitter (PBS) based on a metal
      insulator-metal (MIM) structure inserted into a multimode interference coupler
      (MMI). Owing to the MIM structure, the TE polarized state is reflected by the cut
      off condition while the TM polarized state is transmitted by the surface plasmon
      polariton, and the two polarized states can thus be separated. In this paper, the
      dependence of the reflected TE and transmitted TM field intensities on the MIM
      length and the gap thickness has been studied systematically. The proposed PBS
      structure, with a total size of 4 * 0.7 * 44 um(3) is designed with MIM length,
      gap thickness, and metal thickness of 0.6 um, 0.5 um, and 0.05 um, respectively.
      In the designed PBS, the transmittance for the TM polarized light, reflectance
      for the TE polarized light, extinction ratio, and insertion losses of the TE and
      TM modes are obtained using a 3D finite-difference time-domain method to be 0.9,
      0.88, 12.55 dB, and 1.1 dB and 0.9 dB, respectively. The designed PBS has a much
      shorter length, 44 um, compared to previous PBS devices.

PMID- 24103962
TI  - Graphene-based tunable broadband hyperlens for far-field subdiffraction imaging
      at mid-infrared frequencies.
AB  - Considering the dielectric permittivity of graphene can be tuned to be negative
      by external electric field, we propose to construct alternating
      graphene/dielectric multilayer based optical hyperlens for far-field
      subdiffraction imaging at mid-infrared frequencies. For such a scheme, hyperbolic
      dispersion curve can be achieved under the condition that the thickness of
      dielectric layer is made comparable to that of graphene layer, which is capable
      of supporting the propagation of evanescent wave with large wave vector.
      Simulation results by finite-element method demonstrate that two point sources
      with separation far below the diffraction limit can be magnified by the systems
      to the extent that conventional far-field optical microscopy can further
      manipulate. Such a hyperlens has the advantage of operating in a wideband region
      due to the tunability of graphene's dielectric permittivity as opposed to
      previous metal based hyperlens, enabling the potential applications in real-time
      super-resolution imaging, nanolithography, and sensing. 

PMID- 24103963
TI  - Surface phonon-polariton enhanced optical forces in silicon carbide
      nanostructures.
AB  - The enhanced optical forces induced by surface phonon-polariton (SPhP) modes are
      investigated in different silicon carbide (SiC) nanostructures. Specifically, we
      calculate optical forces using the Maxwell stress tensor for three different
      geometries: spherical particles, slab waveguides, and rectangular waveguides. We
      show that SPhP modes in SiC can produce very large forces, more than one order of
      magnitude larger than the surface plasmon-polariton (SPP) forces in analogous
      metal nanostructures. The material and geometric basis for these large optical
      forces are examined in terms of dispersive permittivity, separation distance, and
      operating wavelength. 

PMID- 24103964
TI  - Temperature effects in tuning fork enhanced interferometric photoacoustic
      spectroscopy.
AB  - Temperature dependent measurements with a compact fiber coupled sensor for trace
      gas detection in the near-infrared based on tuning fork enhanced interferometric
      photoacoustic spectroscopy are presented. The temperature effects on the sensor
      have been investigated in a range from T = -41  degrees C to T = 107  degrees C,
      in particular the influence on the resonance frequency and the Q-factor of the
      micro tuning fork. The refined sensor head contains a combination of a silicon
      tuning fork and an acoustic off-beam resonator and permits methane detection with
      a detection limit of S = (3.85 +/- 0.01) ppm. The functional capability of a
      numerical model for the optimization of acoustic off-beam resonators in COMSOL
      Multiphysics(r) is presented.

PMID- 24103965
TI  - High-repetition-rate, stretch-lens-based actively-mode-locked femtosecond fiber
      laser.
AB  - We propose and demonstrate a novel actively mode-locked fiber laser based on a
      stretch-type time-lens. The pulse generated by this scheme has high repetition
      rate and large bandwidth while no nonlinearity is participated. A 10-GHz chirped
      pulse train with 18-ps duration and 11.6-nm bandwidth is obtained, which is then
      extra-cavity compressed down to 825 fs. The pulse characteristics dependent on
      the cavity dispersion and time-lens strength are discussed. Pulse propagation in
      the laser is similar with dissipative soliton in all-normal-dispersion laser. The
      results demonstrate that the stretch-lens inside the actively mode-locked laser
      can effectively broaden the spectral bandwidth, instead of the fiber
      nonlinearity, which can then support a high-repetition-rate "linear dissipative
      soliton" pulse shaping in a very compact design. 

PMID- 24103966
TI  - Excitability and optical pulse generation in semiconductor lasers driven by
      resonant tunneling diode photo-detectors.
AB  - We demonstrate, experimentally and theoretically, excitable nanosecond optical
      pulses in optoelectronic integrated circuits operating at telecommunication
      wavelengths (1550 nm) comprising a nanoscale double barrier quantum well resonant
      tunneling diode (RTD) photo-detector driving a laser diode (LD). When perturbed
      either electrically or optically by an input signal above a certain threshold,
      the optoelectronic circuit generates short electrical and optical excitable
      pulses mimicking the spiking behavior of biological neurons. Interestingly, the
      asymmetric nonlinear characteristic of the RTD-LD allows for two different
      regimes where one obtain either single pulses or a burst of multiple pulses. The
      high-speed excitable response capabilities are promising for neurally inspired
      information applications in photonics. 

PMID- 24103967
TI  - Broadband photon time-of-flight spectroscopy of pharmaceuticals and highly
      scattering plastics in the VIS and close NIR spectral ranges.
AB  - We present extended spectroscopic analysis of pharmaceutical tablets in the close
      near infrared spectral range performed using broadband photon time-of-flight
      (PTOF) absorption and scattering spectra measurements. We show that the
      absorption spectra can be used to perform evaluation of the chemical composition
      of pharmaceutical tablets without need for chemo-metric calibration. The
      spectroscopic analysis was performed using an advanced PTOF spectrometer
      operating in the 650 to 1400 nm spectral range. By employing temporal
      stabilization of the system we achieve the high precision of 0.5% required to
      evaluate the concentration of tablet ingredients. In order to further illustrate
      the performance of the system, we present the first ever reported broadband
      evaluation of absorption and scattering spectra from pure and doped
      Spectralon(r). 

PMID- 24103968
TI  - About the role of phase matching between a coated microsphere and a tapered
      fiber: experimental study.
AB  - Coatings of spherical optical microresonators are widely employed for different
      applications. Here the effect of the thickness of a homogeneous coating layer on
      the coupling of light from a tapered fiber to a coated microsphere has been
      studied. Spherical silica microresonators were coated using a 70SiO(2)- 30HfO(2)
      glass doped with 0.3 mol% Er(3+) ions. The coupling of a 1480 nm pump laser
      inside the sphere has been assessed using a tapered optical fiber and observing
      the 1530-1580 nm Er(3+) emission outcoupled to the same tapered fiber. The
      measurements were done for different coating thicknesses and compared with
      theoretical calculations to understand the relationship of the detected signal
      with the whispering gallery mode electric field profiles.

PMID- 24103969
TI  - Submicrometer 3D structures fabrication enabled by one-photon absorption direct
      laser writing.
AB  - We demonstrate a new 3D fabrication method to achieve the same results as those
      obtained by the two-photon excitation technique, by using a simple one-photon
      elaboration method in a very low absorption regime. Desirable 2D and 3D
      submicrometric structures, such as spiral, chiral, and woodpile architectures,
      with feature size as small as 190 nm have been fabricated, by using just a few
      milliwatts of a continuous-wave laser at 532 nm and a commercial SU8 photoresist.
      Different aspects of the direct laser writing based on ultralow one-photon
      absorption (LOPA) technique are investigated and compared with the TPA technique,
      showing several advantages, such as simplicity and low cost. 

PMID- 24103970
TI  - A mathematical model of the single freeform surface design for collimated beam
      shaping.
AB  - Incoherent collimated beam has a wide application, and reshaping the collimated
      beam with freeform optics has become a popular and challenging topic of
      noniamging design. In this paper, we address this issue, embedded in three
      dimensional space without any symmetry, with a freeform surface from a new
      perspective. A mathematical model is established for achieving the one-freeform
      surface design based on the problem of optimal mass transport. A numerical
      technique for solving this design model is disclosed for the first time, and
      boundary conditions for balancing light are presented. Besides, some key issues
      in achieving complex illuminations are addressed, and the influence of caustic
      surface on this design model is also discussed. Design examples are given to
      verify these theories. The results show elegance of the design model in tackling
      complex illumination tasks. The conclusions obtained in this paper can be
      generalized to achieve LED illumination and tackle multiple freeform surfaces
      illumination design. 

PMID- 24103971
TI  - Efficient 1856 nm emission from Tm,Mg:LiNbO3 laser.
AB  - Efficient continuous-wave laser emission at 1856 nm from a Tm,Mg:LiNbO(3) crystal
      slab with high Tm(3+) doping concentration is reported. A maximum output power of
      2.62 W is realized with a slope efficiency of 19.6% and the beam quality factor
      M(2) of 1.7 at room temperature. We believe that this is the first demonstration
      of watt-level laser operation in Tm,Mg:LiNbO(3) crystal and the output power is
      four orders of magnitude higher than that reported previously in Tm-doped
      LiNbO(3) crystal. Performance degradation due to the photorefractive effect under
      high intensity 1856 nm laser is not observed thanks to the co-doping of magnesium
      ions. Quantitative analysis about the long-term photorefractive effect is also
      provided. Multi-wavelength laser operation is realized by using different narrow
      band output couplers. This demonstration opens up a viable pathway towards 2-MUm
      integrated optic devices for achieving laser oscillation, electro-optic and
      nonlinear optical effects within just one sample simultaneously.

PMID- 24103972
TI  - SFDR enhancement in analog photonic links by simultaneous compensation for
      dispersion and nonlinearity.
AB  - A method to improve the spurious-free dynamic range (SFDR) of analog photonic
      links has been proposed and experimentally demonstrated, which only consists of a
      phase modulator (PM), a polarizer and an optical filter. Such structure could
      compensate for the chromatic dispersion and the nonlinearity of the modulator
      simultaneously. In addition, by adjusting the states of polarization (SOPs)
      launching into the PM and the polarizer, the proposed scheme could also be
      reconfigured to mitigate the second harmonic nonlinearity induced by the
      photodetector. Experimental results show that the suppressions of the second
      order and third-order intermodulation distortions (IMD2 & IMD3) are larger than
      14-dB and 25.4-dB, respectively. Furthermore, the SFDR can achieve ~110-dB .
      Hz(4/5) for 40-km fiber transmission, which is 26-dB higher than that of the link
      without compensation.

PMID- 24103973
TI  - Rapid 3D light-sheet microscopy with a tunable lens.
AB  - The in-vivo investigation of highly dynamic biological samples, for example the
      beating zebrafish heart, requires high-speed volume imaging techniques. Light
      sheet microscopy is ideal for such samples as it records high-contrast images of
      entire planes within large samples at once. However, in order to obtain images of
      different planes, it has been necessary to move the sample relative to the fixed
      focal plane of the detection objective lens. This mechanical movement limits
      speed, precision and may be harmful to the sample. We have built a light-sheet
      microscope that uses remote focusing with an electrically tunable lens (ETL).
      Without moving specimen or objective we have thereby achieved flexible volume
      imaging at much higher speeds than previously reported. Our high-speed microscope
      delivers 3D snapshots of sensitive biological samples. As an example, we imaged
      17 planes within a beating zebrafish heart at 510 frames per second, equivalent
      to 30 volume scans per second. Movements, shape changes and signals across the
      entire volume can be followed which has been impossible with existing
      reconstruction techniques. 

PMID- 24103974
TI  - Fluoro-graphene: nonlinear optical properties.
AB  - In the present work, we report on the investigation of the third-order nonlinear
      optical response of graphene fluoride dispersed in DMF and also of
      fluorosurfactant-stabilized graphene fluoride dispersed in water under visible
      (532 nm) and infrared (1064 nm), picosecond and nanosecond laser excitation. Both
      graphene derivatives were found to exhibit large nonlinear optical response,
      while significant differences on their nonlinear optical response have been
      observed (e.g. different sign of nonlinear refraction and absorption). These
      findings highlight the important role of the degree of fluorination of the
      graphene sheets on their optical and electronic properties. Furthermore, DMF
      dispersed graphene fluoride was found to exhibit important broadband optical
      limiting action under nanosecond laser excitation, making it promising candidate
      for optical limiting applications.

PMID- 24103976
TI  - Calibration methods for division-of-focal-plane polarimeters.
AB  - Division-of-focal plane (DoFP) imaging polarimeters are useful instruments for
      measuring polarization information for a variety of applications. Recent advances
      in nanofabrication have enabled the practical manufacture of DoFP sensors for the
      visible spectrum. These sensors are made by integrating nanowire polarization
      filters directly with an imaging array, and size variations of the nanowires due
      to fabrication can cause the optical properties of the filters to vary up to 20%
      across the imaging array. If left unchecked, these variations introduce
      significant errors when reconstructing the polarization image. Calibration
      methods offer a means to correct these errors. This work evaluates a scalar and
      matrix calibration derived from a mathematical model of the polarimeter behavior.
      The methods are evaluated quantitatively with an existing DoFP polarimeter under
      varying illumination intensity and angle of linear polarization. 

PMID- 24103978
TI  - Holographic optical element to generate achromatic vortices.
AB  - A compound holographic optical element to generate achromatic vortices with high
      efficiency, based on the combination of two volume phase holograms, is designed
      and constructed. This element is compact and easy to align. It has high damage
      threshold, so it can be used with ultraintense laser pulses. 

PMID- 24103980
TI  - 640 Gbaud (1.28 Tbit/s/ch) optical Nyquist pulse transmission over 525 km with
      substantial PMD tolerance.
AB  - We report a substantial increase in PMD tolerance in a single-channel ultrahigh
      speed transmission using optical Nyquist pulses. We demonstrate both analytically
      and experimentally a large reduction in depolarization-induced crosstalk with
      optical Nyquist pulses, which is one of the major obstacles facing polarization
      multiplexed ultrashort pulse transmission. By taking advantage of the high PMD
      tolerance, a low-penalty 1.28 Tbit/s/ch optical Nyquist TDM transmission at 640
      Gbaud was achieved over 525 km. 

PMID- 24103982
TI  - Selection and generation of multipass modes in an open resonator.
AB  - The original numerical wave model of the open resonator has been employed in the
      investigation of conditions for multipass mode generation. It is shown that for
      Fresnel numbers larger than unity, multiple reflections of radiation from the
      stable resonator mirrors lead to sustained quasi-stationary oscillations which
      are indicative of multipass mode generation. Various types of ray trajectories
      have been considered at the paraxial resonance conditions. Trajectory selecting
      techniques are suggested to provide the high quality output beams at large
      Fresnel numbers. The results of numerical experiments on amplitude-phase
      distribution of output radiation are presented for the suggested schemes. 

PMID- 24103983
TI  - Hybrid terahertz plasmonic waveguide for sensing applications.
AB  - The suitability of a terahertz plasmonic sensor for sensing applications is
      successfully demonstrated using a hybrid planar waveguide composed of a
      subwavelength plastic ribbon waveguide and a diffraction metal grating. The
      subwavelength-confined terahertz plasmons on the hybrid waveguide resonantly
      reflect from the periodic metal structure under phase-matched conditions and
      perform resonant transmission dips. The resonant plasmonic frequencies are found
      to be strongly dependent on the refractive indices and thicknesses of analytes
      laid on the hybrid planar waveguide. Both plastic films with varying thicknesses
      and granular analytes in different quantities are successfully identified
      according to the spectral shifts of resonant dips. An optimal refractive index
      sensitivity of 261 GHz per refractive index unit is achieved. Within localized
      and enhanced terahertz plasmonic fields, the minimum detectable optical path
      difference can be reduced to 2.7 MUm corresponding to lambda/289, and the minimum
      detectable amount of analytes in powdered form reaches 17.3 nano-mole/mm(2). The
      sensing technique can be used to detect particles in a chemical reaction or
      monitor pollutants.

PMID- 24103984
TI  - Design and demonstration of a colorless WDM-OFDMA PON system architecture
      achieving symmetric 20-Gb/s transmissions with residual interference
      compensation.
AB  - In this paper, we propose a two-tiered colorless WDM-OFDMA PON system
      architecture that draws strengths from each individual WDM and OFDM PON systems.
      Specifically, the two-tiered architecture enables a colorless transceiver to be
      shared by a group of ONUs, resulting in drastic reduction of the system cost. For
      achieving colorlessness via reusing downstream light sources, we discover the
      residual power of downstream signal unexpectedly springs back after
      transmissions, causing severe interference to the upstream signal, and thus
      limiting the data rate of the upstream signal. We devise a method of adopting a
      common dispersion compensation module at OLT to reduce the residual power over
      all wavelengths. Experimental results show that, with an improvement of upstream
      signal's SNR up to 10 dB, the system successfully achieves 20-Gb/s bidirectional
      OFDM-signal transmissions on the same wavelength over a 20-km SMF.

PMID- 24103985
TI  - Monostatic coaxial 1.5 MUm laser Doppler velocimeter using a scanning Fabry-Perot
      interferometer.
AB  - We present a laser Doppler velocimeter (LDV) in monostatic coaxial arrangement
      consisting of off-the-shelf telecom-grade components: a single frequency laser
      (wavelength lambda = 1.5 MUm) and a high-finesse scanning Fabry-Perot
      interferometer (sFPI). In contrast to previous 1.5 MUm LDV systems based on
      heterodyne detection, our sFPI-LDV has the advantages of having large remote
      sensing range not limited by laser coherence, high velocity dynamic range not
      limited by detector bandwidth and inherent sign discrimination of Doppler shift.
      The more optically efficient coaxial arrangement where transmitter and receiver
      optics share a common axis reduces the number of components and greatly
      simplifies the optical alignment. However, the sensitivity to unwanted
      backreflections is increased. To circumvent this problem, we employ a custom
      optical circulator design which compared to commercial fiber-optic circulator
      achieves ~40 dB reduction in strength of unwanted reflections (i.e. leakage)
      while maintaining high optical efficiency. Experiments with a solid target
      demonstrate the performance of the sFPI-LDV system with high sensitivity down to
      pW level at present update rates up to 10 Hz. 

PMID- 24103986
TI  - Tuneable Gaussian to flat-top resonator by amplitude beam shaping.
AB  - We outline a simple laser cavity comprising an opaque ring and a circular
      aperture that is capable of producing spatially tuneable laser modes, from a
      Gaussian beam to a Flat-top beam. The tuneability is achieved by varying the
      diameter of the aperture and thus requires no realignment of the cavity. We
      demonstrate this principle using a digital laser with an intra-cavity spatial
      light modulator, and confirm the predicted properties of the resonator
      experimentally. 

PMID- 24103988
TI  - XUV coherent diffraction imaging in reflection geometry with low numerical
      aperture.
AB  - We present an experimental realization of coherent diffraction imaging in
      reflection geometry illuminating the sample with a laser driven high harmonic
      generation (HHG) based XUV source. After recording the diffraction pattern in
      reflection geometry, the data must be corrected before the image can be
      reconstructed with a hybrid-input-output (HIO) algorithm. In this paper we
      present a detailed investigation of sources of spoiling the reconstructed image
      due to the nonlinear momentum transfer, errors in estimating the angle of
      incidence on the sample, and distortions by placing the image off center in the
      computation grid. Finally we provide guidelines for the necessary parameters to
      realize a satisfactory reconstruction within a spatial resolution in the range of
      one micron for an imaging scheme with a numerical aperture NA < 0.03. 

PMID- 24103987
TI  - Absolute phase measurement in fringe projection using multiple perspectives.
AB  - A technique for absolute phase measurement in fringe projection for shape
      measurement is presented. A standard fringe projection system is used, comprising
      a camera and a projector fixed relative to each other. The test object is moved
      to different orientations relative to the fringe projection system. Using the
      system calibration parameters, the technique identifies homologous surface areas
      imaged from different perspectives and resolves the 2 pi phase ambiguity between
      them simultaneously. The technique is also used to identify regions of the phase
      maps corresponding to discrete surfaces on the object. The methods described are
      suitable for automatic shape measurement with a lightweight fringe projection
      probe mounted to a coordinate measuring machine.

PMID- 24103989
TI  - Improved calibration of SOIR/Venus Express spectra.
AB  - The SOIR instrument on board the ESA Venus Express mission has been operational
      since the insertion of the satellite around Venus in April 2006. Since then, it
      has delivered high quality IR solar occultation spectra of the atmosphere of
      Venus. The different steps from raw spectra to archived data are described and
      explained in detail here. These consist of corrections for the dark current and
      for the non-linearity of the detector; removing bad pixels, as well as deriving
      noise. The spectral calibration procedure is described, along with all ancillary
      data necessary for the understanding and interpretation of the SOIR data. These
      include the full characterization of the AOTF filter, one of the major elements
      of the instrument. All these data can be found in the ESA PSA archive. 

PMID- 24103990
TI  - Spectral relationships for atmospheric correction. I. Validation of red and near
      infra-red marine reflectance relationships.
AB  - The present study provides an extensive overview of red and near infra-red (NIR)
      spectral relationships found in the literature and used to constrain red or NIR
      modeling schemes in current atmospheric correction (AC) algorithms with the aim
      to improve water-leaving reflectance retrievals, rhow(lambda), in turbid waters.
      However, most of these spectral relationships have been developed with restricted
      datasets and, subsequently, may not be globally valid, explaining the need of an
      accurate validation exercise. Spectral relationships are validated here with
      turbid in situ data for rhow(lambda). Functions estimating rhow(lambda) in the
      red were only valid for moderately turbid waters (rhow(lambdaNIR) < 3.10(-3)). In
      contrast, bounding equations used to limit rhow(667) retrievals according to the
      water signal at 555 nm, appeared to be valid for all turbidity ranges presented
      in the in situ dataset. In the NIR region of the spectrum, the constant NIR
      reflectance ratio suggested by Ruddick et al. (2006) (Limnol. Oceanogr. 51, 1167
      1179), was valid for moderately to very turbid waters (rhow(lambdaNIR) < 10(-2))
      while the polynomial function, initially developed by Wang et al. (2012) (Opt.
      Express 20, 741-753) with remote sensing reflectances over the Western Pacific,
      was also valid for extremely turbid waters (rhow(lambdaNIR) > 10(-2)). The
      results of this study suggest to use the red bounding equations and the
      polynomial NIR function to constrain red or NIR-modeling schemes in AC processes
      with the aim to improve rhow(lambda) retrievals where current AC algorithms fail.

PMID- 24103991
TI  - Spectral relationships for atmospheric correction. II. Improving NASA's standard
      and MUMM near infra-red modeling schemes.
AB  - Spectral relationships, reflecting the spectral dependence of water-leaving
      reflectance, rhow(lambda), can be easily implemented in current AC algorithms
      with the aim to improve rhow(lambda) retrievals where the algorithms fail. The
      present study evaluates the potential of spectral relationships to improve the
      MUMM [Ruddick et al., 2006, Limnol. Oceanogr. 51, 1167-1179] and standard NASA
      [Bailey et al., 2010, Opt. Express 18, 7521-7527] near infra-red (NIR) modeling
      schemes included in the AC algorithm to account for non-zero rhow(lambdaNIR),
      based on in situ coastal rhow(lambda) and simulated Rayleigh corrected
      reflectance data. Two modified NIR-modeling schemes are investigated: (1) the
      standard NASA NIR-modeling scheme is forced with bounding relationships in the
      red spectral domain and with a NIR polynomial relationship and, (2) the constant
      NIR rhow(lambda) ratio used in the MUMM NIR-modeling scheme is replaced by a NIR
      polynomial spectral relationship. Results suggest that the standard NASA NIR
      modeling scheme performs better for all turbidity ranges and in particular in the
      blue spectral domain (percentage bias decreased by approximately 50%) when it is
      forced with the red and NIR spectral relationships. However, with these new
      constraints, more reflectance spectra are flagged due to non-physical Chlorophyll
      a concentration estimations. The new polynomial-based MUMM NIR-modeling scheme
      yielded lower rhow(lambda) retrieval errors and particularly in extremely turbid
      waters. However, including the polynomial NIR relationship significantly
      increased the sensitivity of the algorithm to errors on the selected aerosol
      model from nearby clear water pixels. 

PMID- 24103992
TI  - Brillouin scattering of visible and hard X-ray photons from optically synthesized
      phonon wavepackets.
AB  - We monitor how destructive interference of undesired phonon frequency components
      shapes a quasi-monochromatic hypersound wavepacket spectrum during its local real
      time preparation by a nanometric transducer and follow the subsequent decay by
      nonlinear coupling. We prove each frequency component of an optical
      supercontinuum probe to be sensitive to one particular phonon wavevector in bulk
      material and cross-check this by ultrafast x-ray diffraction experiments with
      direct access to the lattice dynamics. Establishing reliable experimental
      techniques with direct access to the transient spectrum of the excitation is
      crucial for the interpretation in strongly nonlinear regimes, such as soliton
      formation. 

PMID- 24103993
TI  - Complete wavefront and polarization control for ultrashort-pulse laser
      microprocessing.
AB  - We report on new developments in wavefront and polarization control for
      ultrashort-pulse laser microprocessing. We use two Spatial Light Modulators in
      combination to structure the optical fields of a picosecond-pulse laser beam,
      producing vortex wavefronts and radial or azimuthal polarization states. We also
      carry out the first demonstration of multiple first-order beams with vortex
      wavefronts and radial or azimuthal polarization states, produced using Computer
      Generated Holograms. The beams produced are used to nano-structure a highly
      polished metal surface. Laser Induced Periodic Surface Structures are observed
      and used to directly verify the state of polarization in the focal plane and help
      to characterize the optical properties of the setup. 

PMID- 24103994
TI  - Distributed Raman amplification using ultra-long fiber laser with a ring cavity:
      characteristics and sensing application.
AB  - Distributed Raman amplification (DRA) based on ultra-long fiber laser (UL-FL)
      pumping with a ring cavity is promising for repeaterless transmission and
      sensing. In this work, the characteristics (including gain, nonlinear impairment
      and noise figure) for forward and backward pumping of the ring-cavity based DRA
      scheme are fully investigated. Furthermore, as a typical application of the
      proposed configuration, ultra-long-distance distributed sensing with Brillouin
      optical time-domain analysis (BOTDA) over 142.2 km fiber with 5m spatial
      resolution and +/- 1.5  degrees C temperature uncertainty is achieved, without
      any repeater. The key point for the significant performance improvement is the
      system could offer both of uniform gain distribution and considerably suppressed
      pump-probe relative intensity noise (RIN) transfer, by optimized design of system
      structure and parameters.

PMID- 24103995
TI  - Fiber-connected UWB sensor network for high-resolution localization using optical
      time-division multiplexing.
AB  - A fiber-connected ultra-wideband (UWB) sensor network for high-resolution
      localization which consists of a central station and several sensor nodes is
      proposed and demonstrated. To make the central station easily identify the
      received UWB pulses from different sensor nodes, optical time-division
      multiplexing (OTDM), realized by inserting a certain length of optical fiber
      between every two sensor nodes, is implemented. Due to the OTDM technology, the
      UWB pulses received by different sensors are mapped into different time slots, so
      neither parameter estimation nor clock synchronization is required in the UWB
      sensor node. All complex signal processing is completed in the central station,
      which greatly improve the localization accuracy and simplify the system. A proof
      of-concept experiment for two-dimensional localization is demonstrated. Spatial
      resolution as high as 3.9 cm is achieved. 

PMID- 24103996
TI  - Counterdiabatic mode-evolution based coupled-waveguide devices.
AB  - The goal in designing mode-evolution based devices is to realise short and high
      fidelity components. The counterdiabatic protocol in coherent quantum state
      control can be used to cancel unwanted coupling between adiabatic modes in mode
      evolution but is not directly realisable in the coupled-waveguide system. By
      finding alternative coupled-mode equations that links to the same interaction
      picture dynamical equation as the counterdiabatic protocol via unitary
      transformations, we have derived a universal formalism for the design of short
      and high-fidelity mode-evolution based coupled-waveguide devices. Starting from a
      traditional adiabatic device design, the counterdiabatic protocol leads to a high
      fidelity device, with its evolution following the adiabatic modes exactly even
      when the adiabatic condition is violated. Tolerance analysis shows that the
      countera-diabatic devices combine the advantages of adiabatic and resonant
      devices. The formalism is used to design asymmetric waveguide couplers. 

PMID- 24103997
TI  - Modeling of spectral and statistical properties of a random distributed feedback
      fiber laser.
AB  - For the first time we report full numerical NLSE-based modeling of generation
      properties of random distributed feedback fiber laser based on Rayleigh
      scattering. The model which takes into account the random backscattering via its
      average strength only describes well power and spectral properties of random DFB
      fiber lasers. The influence of dispersion and nonlinearity on spectral and
      statistical properties is investigated. The evidence of non-gaussian intensity
      statistics is found. 

PMID- 24103998
TI  - Four-wave mixing analysis on injection-locked quantum dot semiconductor lasers.
AB  - We derive a simplified rate equation model for the four-wave mixing (FWM)
      analysis on quantum dot (QD) semiconductor lasers subject to optical injection.
      The regenerative and the amplitude modulation spectra of the FWM signals with
      different intrinsic laser parameters and external injection conditions are
      investigated. By curve fitting the regenerative and the amplitude modulation
      spectra obtained experimentally, the intrinsic parameters of a commercial single
      mode QD laser under different injection conditions are extracted. The linewidth
      enhancement factor alpha at different injection levels and detunings are shown,
      where a reduction of up to 39% from its free-running value is demonstrated. By
      increasing the injection strength, the alpha can be further reduced to minimized
      the chirp in optical communications. 

PMID- 24103999
TI  - Study of the thermo-optical constants of Yb doped Y2O3, Lu2O3 and Sc2O3 ceramic
      materials.
AB  - Thermally induced depolarization and thermal lens of three Konoshima Chemical Co.
      laser-ceramics samples Yb(3+):Lu(2)O(3)(C(Yb) ~ 1.8 at.%), Yb(3+):Y(2)O(3)(C(Yb)
      ~ 1.8 at.%), and Yb(3+):Sc(2)O(3) (C(Yb) ~ 2.5 at.%) were measured in experiment
      at different pump power. The results allowed us to estimate the thermal
      conductivity of the investigated ceramic samples and compare their thermo-optical
      properties. The thermo-optical constants P and Q and its sign measured for these
      materials at the first time.

PMID- 24104000
TI  - Pulfrich autostereo display with micro-prism array.
AB  - A micro-prism film, with spectral characteristics, is attached on a display panel
      to show images appearing with + 10 degrees  ~ + 50 degrees  and -10 degrees  ~-50
      degrees  bright regions and with a + 10 degrees  ~-10 degrees  dark region. When
      both eyes separately receive the bright region and the dark region of an image,
      interocular delay would appear to generate a stereo perception. With the optical
      simulation software, LightTools 7.3.0, to simulate the brightness change, the
      light with lower brightness appears on the 0 degrees  region and the light with
      the highest brightness appears on the +/- 10 degrees  region. The optimal viewing
      distance of 25 cm could accurately deliver the image with shading parallax to
      both eyes. The actual measurement of brightness presents the shading
      distribution, achieving the condition of binocular retinal illumination, and the
      angle of visibility appears on the +/- 50 degrees  region, causing interocular
      delay so that the viewer generates the stereo perception.

PMID- 24104001
TI  - Reverse design of a bull's eye structure based on the plasmonic far-field
      pattern.
AB  - We present a novel concept on designing a bull's eye structure for a single
      wavelength optical source. The plasmonic far-field around a subwavelength
      aperture on a thin gold film is calculated by finite-difference time-domain
      method. Based on the annular field intensity distribution on the film surface, we
      present a method for determining a fairly optimal first groove radius and a
      periodicity of the grooves that show enhanced transmission. By additionally fine
      tuning groove width and groove depth, we have achieved a transmission factor of
      9.74. Our novel method has high potential in applications such as silicon
      infrared sensors. 

PMID- 24104002
TI  - Design and characterization of low loss 50 picoseconds delay line on SOI
      platform.
AB  - We design and experimentally demonstrate 50 picoseconds (ps) low loss delay line
      on 300 nm SOI platform. The delay line unit consists of straight rib waveguide
      and strip bend section linked by a transition taper waveguide. Low propagation
      loss of ~0.1 dB/cm is achieved on the straight rib waveguide. With taking into
      account both low loss and desirable delay, a complete design and characterization
      process for passive delay line is presented. Our measurement results show that
      about 0.7 dB excess loss is achievable for 50 ps delay. The loss can be further
      reduced by adjusting the layout parameters. 

PMID- 24104003
TI  - Integration of microfluidics with grating coupled silicon photonic sensors by one
      step combined photopatterning and molding of OSTE.
AB  - We present a novel integration method for packaging silicon photonic sensors with
      polymer microfluidics, designed to be suitable for wafer-level production
      methods. The method addresses the previously unmet manufacturing challenges of
      matching the microfluidic footprint area to that of the photonics, and of robust
      bonding of microfluidic layers to biofunctionalized surfaces. We demonstrate the
      fabrication, in a single step, of a microfluidic layer in the recently introduced
      OSTE polymer, and the subsequent unassisted dry bonding of the microfluidic layer
      to a grating coupled silicon photonic ring resonator sensor chip. The
      microfluidic layer features photopatterned through holes (vias) for optical fiber
      probing and fluid connections, as well as molded microchannels and tube
      connectors, and is manufactured and subsequently bonded to a silicon sensor chip
      in less than 10 minutes. Combining this new microfluidic packaging method with
      photonic waveguide surface gratings for light coupling allows matching the size
      scale of microfluidics to that of current silicon photonic biosensors. To
      demonstrate the new method, we performed successful refractive index measurements
      of liquid ethanol and methanol samples, using the fabricated device. The minimum
      required sample volume for refractive index measurement is below one nanoliter. 

PMID- 24104004
TI  - Measurement depth enhancement in terahertz imaging of biological tissues.
AB  - We demonstrate the use of a THz penetration-enhancing agent (THz-PEA) to enhance
      the terahertz (THz) wave penetration depth in tissues. The THz-PEA is a
      biocompatible material having absorption lower than that of water, and it is
      easily absorbed into tissues. When using glycerol as a THz-PEA, the peak value of
      the THz signal which was transmitted through the fresh tissue and reflected by a
      metal target, was almost doubled compared to that of tissue without glycerol. THz
      time-of-flight imaging (B-scan) was used to display the sequential glycerol
      delivery images. Enhancement of the penetration depth was confirmed after an
      artificial tumor was located below fresh skin. We thus concluded that the THz-PEA
      technique can potentially be employed to enhance the image contrast of the
      abnormal lesions below the skin. 

PMID- 24104005
TI  - Improving the retrieval of water inherent optical properties in noisy
      hyperspectral data through statistical modeling.
AB  - The use of the Mahalanobis distance in a lookup table approach to retrieval of in
      water Inherent Optical Properties (IOPs) led to significant improvements in the
      accuracy of the retrieved IOPs, as high as 50% in some cases, with an average
      improvement of 20% over a wide range of case II waters. Previous studies have
      shown that inherent noise in hyperspectral data can cause significant errors in
      the retrieved IOPs. For LUT-based retrievals that rely on spectrum matching, the
      particular metric used for spectral comparisons has a significant effect on the
      accuracy of the results, especially in the presence of noise in the data. In this
      study, we have compared the Euclidean distance and the Mahalanobis distance as
      metrics for spectral comparison. In addition to providing justification for the
      preference of the Mahalanobis Distance over the Euclidean Distance, we have also
      included a statistical description of noisy hyperspectral data. 

PMID- 24104006
TI  - Electromagnetic waves in a topological insulator thin film stack: helicon-like
      wave mode and photonic band structure.
AB  - We theoretically explore the electromagnetic modes specific to a topological
      insulator superlattice in which topological and conventional insulator thin films
      are stacked periodically. In particular, we obtain analytic formulas for low
      energy mode that corresponds to a helicon wave, as well as those for photonic
      bands. We illustrate that the system can be modeled as a stack of quantum Hall
      layers whose conductivity tensors alternately change signs, and then we analyze
      the photonic band structures. This subject is a natural extension of a previous
      study by Tselis et al., which took into consideration a stack of identical
      quantum Hall layers but their discussion was limited into a low energy mode. Thus
      we provide analytic formulas for photonic bands and compare their features
      between the two systems. Our central findings in the topological insulator
      superlattice are that a low energy mode corresponding to a helicon wave has
      linear dispersion instead of the conventional quadratic form, and that a robust
      gapless photonic band appears although the system considered has spacial
      periodicity. In addition, we demonstrate that the photonic bands agree with the
      numerically calculated transmission spectra. 

PMID- 24104007
TI  - Time-resolved photoluminescence of silicon microstructures fabricated by
      femtosecond laser in air.
AB  - Green photoluminescence (PL) from silicon microstructures fabricated by
      femtosecond laser in air was studied at different temperature by time-resolved
      spectroscopy. The PL decay profiles are well fitted by a stretched exponential
      function: I(t)=I(0)*exp[-(t/tau)beta]. The dependence of the decay time constant
      tau and of the stretching index beta on PL photon energy and on the temperature
      is investigated. A model of transport and recombination of the carriers is
      introduced as a possible explanation of the stretched exponential decay. The
      nonradiative recombination rate of the localized carriers, which is dependent on
      the carrier density and influenced by the trapping site density and the
      temperature, is deduced to be responsible for this kind of decay.

PMID- 24104008
TI  - Intense supercontinuum generation exceeding 300eV using a two-color field in
      combination with a 400-nm few-cycle control pulse.
AB  - We propose a method to control the harmonic process by using a two-color field in
      combination with a 400-nm few-cycle control pulse for the generation of an ultra
      broadband supercontinuum with high efficiency. The ionization and acceleration
      steps in the harmonic process can be simultaneously controlled by using a three
      color field synthesized by a 2000-nm driving pulse and two weak 800-nm and 400-nm
      control pulses. Then an intense supercontinuum covered by the spectral range from
      140 eV to 445 eV is produced. The 3D macroscopic propagation is also employed to
      select the short quantum path of the supercontinuum, then intense isolated sub
      100-as pulses with tunable central wavelengths are directly obtained within water
      window region. In addition, the generation of isolated attosecond pulses in the
      far field is also investigated. An isolated 52-as pulse can be generated by using
      a filter centered on axis to select the harmonics in the far field.

PMID- 24104009
TI  - Terahertz wave generation from hyper-Raman lines in two-level quantum systems
      driven by two-color lasers.
AB  - Based on spatial-temporal symmetry breaking mechanism, we propose a novel scheme
      for terahertz (THz) wave generation from hyper-Raman lines associated with the
      0th harmonic (a particular even harmonic) in a two-level quantum system driven by
      two-color laser fields. With the help of analysis of quasi-energy, the frequency
      of THz wave can be tuned by changing the field amplitude of the driving laser. By
      optimizing the parameters of the laser fields, we are able to obtain arbitrary
      frequency radiation in the THz regime with appreciable strength (as strong as the
      typical harmonics). Our proposal can be realized in experiment in view of the
      recent experimental progress of even-harmonics generation by two-color laser
      fields. 

PMID- 24104010
TI  - Optical Kerr phase shift in a nanostructured nickel-doped zinc oxide thin solid
      film.
AB  - The optical Kerr effect exhibited by a nickel doped zinc oxide thin solid film
      was explored with femto- and pico-second pulses using the z-scan method. The
      samples were prepared by the ultrasonic spray pyrolysis technique. Opposite signs
      for the value of the nonlinear refractive index were observed in the two
      experiments. Self-defocusing together with a two-photon absorption process was
      observed with 120 ps pulses at 1064 nm, while a dominantly self-focusing effect
      accompanied by saturated absorption was found for 80 fs pulses at 825 nm.
      Regarding the nanostructured morphology of the resulting film, we attribute the
      difference in the two ultrafast optical responses to the different physical
      mechanism responsible of energy transfer generated by multiphoton processes under
      electronic and thermal effects. 

PMID- 24104011
TI  - Adjustable exciton-photon coupling with giant Rabi-splitting using layer-by-layer
      J-aggregate thin films in all-metal mirror microcavities.
AB  - Developing of highly absorbing thin films is essential for exploration of light
      matter interaction and polariton-based applications. We demonstrate here layer-by
      layer assembled J-aggregate thin films of (DEDOC) cyanine dyes that have high
      absorption coefficient and controlled thicknesses, leading to adjustable exciton
      photon coupling and Rabi splitting exceeding 400 meV at room temperature in all
      metal mirror microcavities. 

PMID- 24104012
TI  - High power 2 um femtosecond fiber laser.
AB  - A high power polarization maintaining femtosecond Tm-doped fiber laser system is
      demonstrated. A chirped fiber Bragg grating with normal dispersion was used to
      compensate the anomalous dispersion from the regular fiber in the 2 um seed
      oscillator to generate mode locked pulses with a pulse repetition rate of 30.84
      MHz. After chirped pulse amplification, an amplified power of 78 W was obtained.
      The pulse was compressed by a chirped volume Bragg grating based pulse
      compressor. A pulse duration of 760 fs and an average power of 36 W were obtained
      after compressor. 

PMID- 24104013
TI  - Spectral tuning of lasing emission from optofluidic droplet microlasers using
      optical stretching.
AB  - We introduce tunable optofluidic microlasers based on active optical resonant
      cavities formed by optically stretched, dye-doped emulsion droplets confined in a
      dual-beam optical trap. To achieve tunable dye lasing, optically pumped droplets
      of oil dispersed in water are stretched by light in the dual-beam trap.
      Subsequently, resonant path lengths of whispering gallery modes (WGMs)
      propagating in the droplet are modified, leading to shifts in the microlaser
      emission wavelengths. Using this technique, we present all-optical, almost
      reversible spectral tuning of the lasing WGMs and show that the direction of
      tuning depends on the position of the pump beam focus on the droplet. In
      addition, we study the effects of temperature changes on the spectral position of
      lasing WGMs and demonstrate that droplet heating leads to red-tuning of the
      droplet lasing wavelength. 

PMID- 24104014
TI  - Graphene/liquid crystal based terahertz phase shifters.
AB  - Due to its high electrical conductivity and excellent transmittance at terahertz
      frequencies, graphene is a promising candidate as transparent electrodes for
      terahertz devices. We demonstrate a liquid crystal based terahertz phase shifter
      with the graphene films as transparent electrodes. The maximum phase shift is
      10.8 degree and the saturation voltage is 5 V with a 50 um liquid crystal cell.
      The transmittance at terahertz frequencies and electrical conductivity depending
      on the number of graphene layer are also investigated. The proposed phase shifter
      provides a continuous tunability, fully electrical controllability, and low DC
      voltage operation. 

PMID- 24104015
TI  - A compact thermo-optical multimode-interference silicon-based 1 * 4 nano-photonic
      switch.
AB  - An ultra-compact multimode-interference (MMI)-based 1 * 4 nano-photonic switch is
      demonstrated by employing silicon thermo-optical effect on SOI platform. The
      device performance is systematically characterized by comprehensively
      investigating the constituent building blocks, including 1 * 4 power splitter, 4
      * 4 MMI coupler and groove-isolated thermo-optical heaters. An instructive model
      is established to statistically estimate the required power consumption and
      investigate the influence of the power imbalance of the 4 * 4 MMI coupler on the
      switching performance. At the designed wavelength of 1550 nm, the average
      insertion loss of different switching states is 1.7 dB, and the transmission
      imbalance is 1.05 dB. The worst extinction ratio and crosstalk of all the output
      ports reach 11.48 dB and -11.38 dB, respectively.

PMID- 24104016
TI  - Plasmon resonance of silver micro-sphere in fiber taper.
AB  - We have experimentally studied the plasmon resonance phenomenon of a silver micro
      sphere with a diameter of 2.3 MUm in cone-shaped air cavity of a hollow fiber
      taper. To take insight into the plasmon resonance phenomenon, we move the micro
      sphere along the fiber and observe the significant shift of the resonance peak.
      We also explore the light response in both infrared and visible wavelength band
      by finite difference time domain method. The significant variations of the
      magnetic and power field distribution are observed. The interesting results imply
      that the configuration has great potential in optical sensors and color filters.

PMID- 24104017
TI  - Fiber looped phase conjugation of polarization multiplexed signals for pre
      compensation of fiber nonlinearity effect.
AB  - Compensation of nonlinear distortion of polarization-multiplexed (PolMux) signals
      in optical fiber is evaluated experimentally using all-optical signal pre
      distortion and fiber loop phase-conjugation at the transmitter. An improved bit
      error rate is shown for high baud rate, 80 Gb/s RZ-DPSK PolMux signals before
      transmission in a 728 km long dispersion-managed fiber link employing a direct
      detection receiver. The partial compensation of nonlinear distortion for both
      single channel and 3 * 80 Gb/s WDM PolMux signals is observed, despite the impact
      from the inter-polarization nonlinearity and the associated polarization
      scattering. Evidence of the limited compensation of inter-polarization
      nonlinearity is shown. 

PMID- 24104018
TI  - Correlated multielectron dynamics in mid-infrared laser pulse interactions with
      neon atoms.
AB  - The multielectron dynamics in nonsequential triple ionization (NSTI) of neon
      atoms driven by mid-infrared (MIR) laser pulses is investigated with the three
      dimensional classical ensemble model. In consistent with the experimental result,
      our numerical result shows that in the MIR regime, the triply charged ion
      longitudinal momentum spectrum exhibits a pronounced double-hump structure at low
      laser intensity. Back analysis reveals that as the intensity increases, the
      responsible triple ionization channels transform from direct (e, 3e) channel to
      the various mixed channels. This transformation of the NSTI channels leads to the
      results that the shape of ion momentum spectra becomes narrow and the distinct
      maxima shift towards low momenta with the increase of the laser intensity. By
      tracing the triply ionized trajectories, the various ionization channels at
      different laser intensities are clearly identified and these results provide an
      insight into the complex dynamics of the correlated three electrons in NSTI. 

PMID- 24104019
TI  - A novel optical film to provide a highly collimated planar light source.
AB  - In this paper, we proposed a novel optical film 'Collimation Film with Equivalent
      Focal Reflective Aperture' (CFEFRA) that can collocate with the proper light
      guide plate (LGP) to provide a highly collimated planar light source (HCPLS) that
      not only has high intensity peak but also good uniformity. The CFEFRA has micro
      cylindrical lenses and inverted-prism-like micro-teeth on its upper surface and
      lower surface, respectively. The lower micro-teeth that are aligned with the
      upper lenses can deflect the light emitting from the LGP at large declination
      into the normal, and then the deflected light with transverse fan-out is further
      converged by the upper lens to become the collimated light. The exact alignment
      between the upper and lower micro-structures is fulfilled by the method 'auto
      secure-alignment by focusing of a collimated exposure beam'. The vertical and
      horizontal full width at half maximum (FWHM) of angular intensity of the HCPLS
      for the optimal case are of 14 and 6 degrees, respectively. Moreover, it still
      has high optical efficiency with light output of over 90% despite the resultant
      emitting light is such collimated. Most importantly, CFEFRA just needs to
      collocate with a relatively low-cost and easily-manufactured LGP so the HCPLS
      adopting the CFEFRA can be extended for large-sized application. Both optical
      model and experimental samples are demonstrated in this paper, and the simulation
      results are consistent with the experimental results. The consistency proves our
      design concept and optical model are convincible and feasible. 

PMID- 24104020
TI  - High performance GaN-based LEDs on patterned sapphire substrate with patterned
      composite SiO2/Al2O3 passivation layers and TiO2/Al2O3 DBR backside reflector.
AB  - GaN-based light-emitting diodes (LEDs) on patterned sapphire substrate (PSS) with
      patterned composite SiO(2)/Al(2)O(3) passivation layers and TiO(2)/Al(2)O(3)
      distributed Bragg reflector (DBR) backside reflector have been proposed and
      fabricated. Highly passivated Al(2)O(3) layer deposited on indium tin oxide (ITO)
      layer with excellent uniformity and quality has been achieved with atomic layer
      deposition (ALD) technology. With a 60 mA current injection, an enhancement of
      21.6%, 59.7%, and 63.4% in the light output power (LOP) at 460 nm wavelength was
      realized for the LED with the patterned composite SiO(2)/Al(2)O(3) passivation
      layers, the LED with the patterned composite SiO(2)/Al(2)O(3) passivation layers
      and Ag mirror + 3-pair TiO(2)/SiO(2) DBR backside reflector, and the LED with the
      patterned composite SiO(2)/Al(2)O(3) passivation layer and Ag mirror + 3-pair ALD
      grown TiO(2)/Al(2)O(3) DBR backside reflector as compared with the conventional
      LED only with a single SiO(2) passivation layer, respectively.

PMID- 24104021
TI  - Spectral attenuation limits of silica hollow core negative curvature fiber.
AB  - In this paper we discuss the limits of attenuation of silica hollow core negative
      curvature fibers in the wavelength range from 800 nm up to 4.5 um. Both numerical
      and experimental results are presented and show good agreement. A minimum
      attenuation of 24.4 dB/km was measured at around 2400 nm wavelength, while 85
      dB/km was measured at 4000 nm.

PMID- 24104022
TI  - Lipid detection in atherosclerotic human coronaries by spectroscopic
      intravascular photoacoustic imaging.
AB  - The presence of lipids in atherosclerotic coronary lesions is an important
      determinant of their potential to trigger acute coronary events. Spectroscopic
      intravascular photoacoustic imaging (sIVPA) has the potential to automatically
      detect lipids in atherosclerotic lesions. For real-time in vivo imaging, limiting
      the number of excitation wavelengths is crucial. We explored methods for plaque
      lipid detection using sIVPA, with the aim to minimize the number of laser pulses
      per image line. A combined intravascular ultrasound (IVUS) and photoacoustic
      imaging system was used to image a vessel phantom and human coronary arteries ex
      vivo. We acquired co-registered cross-sectional images at several wavelengths
      near 1200 nm, a lipid-specific absorption band. Correlating the photoacoustic
      spectra at 6 or 3 wavelengths from 1185 to 1235 nm with the absorption spectrum
      of cholesterol and peri-adventitial tissue, we could detect and differentiate the
      lipids in the atherosclerotic plaque and peri-adventitial lipids, respectively.
      With two wavelengths, both plaque and peri-adventitial lipids were detected but
      could not be distinguished. 

PMID- 24104023
TI  - Colloidal particle lens arrays-assisted nano-patterning by harmonics of a
      femtosecond laser.
AB  - We consider nanopatterning of dielectric substrates by harmonics of single
      powerful femtosecond pulses from a Ti:Sapphire laser. The nanopatterning is
      mediated by closely packed monolayers of polystyrene microspheres that act as
      microlenses at the surface. Observed modification of the material proceeds via
      ionization. By our theory, the second harmonic is more effective in multi-photon
      ionization and is better focused than the fundamental frequency which is
      effective in multiplying of the amount of free electrons via impact ionization.
      Experiments show that conversion of a part of the pulse energy into the second
      harmonic decreases the modification threshold and improves the localization of
      the structures. Optimization of the time offset between the harmonics could
      further improve the efficiency and quality of nanostructuring. 

PMID- 24104024
TI  - ONU migration in dynamic Time and Wavelength Division Multiplexed Passive Optical
      Network (TWDM-PON).
AB  - We propose a novel Optical Network Units (ONU) migration mechanism within the
      Time and Wavelength Division Multiplexed PON (TWDM-PON) framework by rearranging
      the working ONUs to a minimum number of wavelengths and turning off the rest to
      save power. We show through simulation that the number of working wavelengths can
      be minimized up to a theoretical lower bound, e.g. 23%, under the typical ONU
      online profiles. We further investigate how the migration interval and delay
      influence the user Service Level Agreement (SLA). We find that under the example
      ONU online profiles, 99.99% ONU SLA can be realized with the migration delay of
      1000 milli-seconds. However to realize 99.999% ONU SLA, the migration delay must
      be 100 milli-seconds or lower. 

PMID- 24104025
TI  - Polarisation charges and scattering behaviour of realistically rounded plasmonic
      nanostructures.
AB  - We study the effect of realistically rounding nanorod antennae and gap antennae
      on their far field and near field properties. The simulations show that both
      scattering behaviour and polarisation charge distribution depend significantly on
      rounding. Rounding is also seen to have a major effect on coupling between
      nanostructures. The results suggest that it is important to incorporate the
      effect of rounding to be able to design plasmonic nanostructures with desired
      properties. 

PMID- 24104026
TI  - Quality control of oblique incidence optical coatings based on normal incidence
      measurement data.
AB  - We demonstrate selection of reliable approaches for post-production
      characterization of oblique incidence multilayer optical coatings. The approaches
      include choice of input information, selection of adequate coating model,
      corresponding numerical characterization algorithm, and verification of the
      results. Applications of the approaches are illustrated with post-production
      characterization of oblique incidence edge filter, oblique incidence beam
      splitter and oblique incidence 43-layer quarter-wave mirror. 

PMID- 24104027
TI  - Design and fabrication of ultra-steep notch filters.
AB  - We present the design and production approach of an ultra-steep notch filter. The
      notch filter that does not have thin layers is optimized utilizing the
      constrained optimization technique, and this is well suitable for accurate
      monitoring with the electron beam deposition technique. Single layer SiO(2) and
      Ta(2)O(5) films were deposited and carefully characterized in order to determine
      tooling factors and refractive indices wavelength dependencies accurately. We
      produced the ultra-steep notch filter with indirect monochromatic monitoring
      strategy and demonstrated the excellent correspondence to the theoretical
      spectral performance.

PMID- 24104029
TI  - Giant optical nonlocality near the Dirac point in metal-dielectric multilayer
      metamaterials.
AB  - The giant optical nonlocality near the Dirac point in lossless metal-dielectric
      multilayer metamaterials is revealed and investigated through the analysis of the
      band structure of the multilayer stack in the three-dimensional omega-k space,
      according to the transfer-matrix method with the optical nonlocal effect. The
      position of the Dirac point is analytically located in the omega-k space. It is
      revealed that the emergence of the Dirac point is due to the degeneracy of the
      symmetric and the asymmetric eigenmodes of the coupled surface plasmon
      polaritons. The optical nonlocality induced epsilon-near-zero frequency shift for
      the multilayer stack compared to the effective medium is studied. Furthermore,
      the giant optical nonlocality around the Dirac point is explored with the iso
      frequency contour analysis, while the beam splitting phenomenon at the Dirac
      point due to the optical nonlocal effect is also demonstrated. 

PMID- 24104028
TI  - Predictive control of thermally induced wavefront aberrations.
AB  - In this paper we experimentally demonstrate the proof of concept for predictive
      control of thermally induced wavefront aberrations in optical systems. On the
      basis of the model of thermally induced wavefront aberrations and using only past
      wavefront measurements, the proposed adaptive optics controller is able to
      predict and to compensate the future aberrations. Furthermore, the proposed
      controller is able to correct wavefront aberrations even when some parameters of
      the prediction model are unknown. The proposed control strategy can be used in
      high power optical systems, such as optical lithography machines, where the
      predictive correction of thermally induced wavefront aberrations is a crucial
      issue. 

PMID- 24104030
TI  - Broad parameter optimization of polarization-diversity 2D grating couplers for
      silicon photonics.
AB  - Polarization-diversity couplers, which are designed to couple the unknown
      polarization state of an optical fiber into the TE-polarized modes of integrated
      waveguides, are important for the development of practical all-optical circuits.
      We describe the use of a full 3D finite difference time domain (FDTD) calculation
      campaign to rigorously optimize the 2D photonic crystal grating that couples a
      single-mode telecom fiber to the silicon waveguides of a Silicon-on-Insulator
      (SOI) platform. With this approach we identify the unique optimum combination of
      etch-depth, hole-radius, and grating-pitch of the photonic crystal array for best
      performance at 1550 nm. The mean (polarization-averaged) coupling efficiency of
      48% (-3.2dB) exceeds reported efficiencies of analogous couplers, and has only a
      marginal dependence on the polarization state of the input fiber (48 +/- 3%). In
      addition, 3D-FDTD calculations are used to characterize the propagation
      direction, mode-profile, and polarization of light coupled from the fiber into
      the SOI slab. Such information is crucial for component design and goes beyond
      previously available results from existing approximations and simulations of 2D
      grating coupler performance. Calculations of photonic mode dispersion in the
      grating coupler, by means of guided-mode expansion, indicate that the coupling is
      due to an optically active resonant guided mode in the photonic crystal array.
      This points towards a fast optimization scheme that enhances both the performance
      and the physical interpretation of 3D-FDTD simulations. 

PMID- 24104031
TI  - Phase noise tolerant inter-carrier-interference cancellation for WDM
      superchannels with sub-Nyquist channel spacing.
AB  - We propose and demonstrate a novel multi-input multi-output (MIMO) equalization
      based inter-carrier-interference (ICI) cancellation approach employing constant
      modulus algorithm (CMA) for supperchanels with sub-Nyquist channel spacing, where
      optical combs are used as optical sources. Compared with the least mean square
      (LMS) algorithm based ICI canceller, the proposed approach has comparable
      capability to accomplish the ICI mitigation for 56 Gbaud dual-polarization
      quadrature phase shift keying (DP-QPSK) signals with tight channel spacing till
      50 GHz. In particular, compared with the LMS-MIMO based ICI canceller, the
      optical linewidth tolerance of 6 MHz is relaxed to 20 MHz given a 1dB required
      optical signal-to-noise ratio (OSNR) penalty for the CMA-MIMO based ICI
      canceller. Meanwhile, the CMA-MIMO based ICI canceller is ideal for real-time
      processing, since the number of parallel processing pipelines can be greater than
      240 even in the presence of large linewidth. 

PMID- 24104032
TI  - Laser induced breakdown spectroscopy of pure aluminum with high temporal
      resolution.
AB  - We report on a Laser Induced Breakdown Spectroscopy (LIBS) system with a very
      high temporal resolution, using femtosecond and picosecond pulse laser excitation
      of pure aluminum (Al). By using a 140 fs Ti:Sapphire laser in an ultrafast
      optical Kerr gate (OKG), we demonstrate LIBS sampling with a sub-ps time
      resolution (0.8 +/- 0.08 ps) in a 14 ns window. The width of the gating window in
      this system was as narrow as 0.8 ps, owing to the inclusion of a carbon disulfide
      (CS(2)) cell, which has a fast response and a large nonlinear coefficient.
      Furthermore, when using a 100 ps pulsed Nd:YAG laser and a fast photomultiplier
      tube (PMT) we demonstrate a LIBS system with a nanosecond time resolution (2.20
      +/- 0.08 ns) in a microsecond window. With this sort of temporal resolution, a
      non-continuous decay in the Al signal could be observed. After 50 ns decay of the
      first peak, the second peak at 230 ns is started to perform. Experimental results
      with such short temporal windows in LIBS, in both nanosecond and microsecond
      ranges, are important for fast temporal evolution measurements and observations
      of early continuum emission in materials.

PMID- 24104033
TI  - Integrated nonlinear Mach Zehnder for 40 Gbit/s all-optical switching.
AB  - We report on the experimental demonstration of a novel silicon based fully
      integrated nonlinear Mach Zehnder device. A standard silicon waveguide is used as
      a nonlinear arm, conversely a large mode SU-8 waveguide acts as a purely linear
      arm. Given this asymmetry, an intensity dependent phase shift can be introduced
      between the two interferometric arms. Thanks to a fine tuning of the silicon arm
      optical properties, a low power, ultrafast, picosecond operation is demonstrated,
      allowing the use of this device for ultrafast all-optical signal processing in
      high density communication networks. 

PMID- 24104034
TI  - Optical temperature sensing of NaYbF4: Tm3+@SiO2 core-shell micro-particles
      induced by infrared excitation.
AB  - NaYbF(4):Tm3+@SiO(2) core-shell micro-particles were synthesized by a
      hydrothermal method and subsequent ultrasonic coating process. Optical
      temperature sensing has been observed in NaYbF4: Tm(3+)@SiO(2)core-shell micro
      particles with a 980 nm infrared laser as excitation source.The fluorescence
      intensity ratios, optical temperature sensitivity, and temperature dependent
      population re-distribution ability from the thermally coupled (1)D(2)/(1)G(4) and
      (3)F(2) /(3)H(4) levels of the Tm(3+) ion have been analyzed as a function of
      temperature in the range of 100~700 K in order to check its availability as a
      optical temperature sensor. A better behavior as a lowtemperature sensor has been
      obtained with a minimum sensitivity of 5.4 * 10(-4) K(-1) at 430 K. It exhibits
      temperature induced population re-distribution from (1)D(2) /(1)G(4) thermally
      coupled levels at higher temperature range.

PMID- 24104035
TI  - Probe-sample optical interaction: size and wavelength dependence in localized
      plasmon near-field imaging.
AB  - The probe-sample optical interaction in apertureless near-field optical
      microscopy is studied at 633 nm and 808 nm excitation wavelengths using gold
      nanodisks as model systems. The near-field distributions of the dipolar and
      quadrupolar surface plasmon modes have been mapped successfully using metal
      coated probes with different polarization combinations of excitation and
      detection except when the incident and the scattered light polarizations are
      chosen to be parallel to the probe axis. For the parallel polarization of the
      incident and the scattered light, the pattern of the near-field distribution
      differs from the inherent plasmon mode structures of the sample, depending
      sensitively on the sample size and excitation energy. For a given excitation
      energy, the near-field amplitude shifts from one pole to the other as the sample
      size increases, having nearly equal amplitude at the two poles when the plasmon
      resonance peak spectrally overlaps with the excitation energy. 

PMID- 24104036
TI  - Coherent time-stretch transformation for real-time capture of wideband signals.
AB  - Time stretch transformation of wideband waveforms boosts the performance of
      analog-to-digital converters and digital signal processors by slowing down analog
      electrical signals before digitization. The transform is based on dispersive
      Fourier transformation implemented in the optical domain. A coherent receiver
      would be ideal for capturing the time-stretched optical signal. Coherent
      receivers offer improved sensitivity, allow for digital cancellation of
      dispersion-induced impairments and optical nonlinearities, and enable decoding of
      phase-modulated optical data formats. Because time-stretch uses a chirped
      broadband (>1 THz) optical carrier, a new coherent detection technique is
      required. In this paper, we introduce and demonstrate coherent time stretch
      transformation; a technique that combines dispersive Fourier transform with
      optically broadband coherent detection. 

PMID- 24104037
TI  - A chip-scale, telecommunications-band frequency conversion interface for quantum
      emitters.
AB  - We describe a chip-scale, telecommunications-band frequency conversion interface
      designed for low-noise operation at wavelengths desirable for common single
      photon emitters. Four-wave-mixing Bragg scattering in silicon nitride waveguides
      is used to demonstrate frequency upconversion and downconversion between the 980
      nm and 1550 nm wavelength regions, with signal-to-background levels > 10 and
      conversion efficiency of ~ -60 dB at low continuous wave input pump powers (< 50
      mW). Finite element simulations and the split-step Fourier method indicate that
      increased input powers of ~ 10 W (produced by amplified nanosecond pulses, for
      example) will result in a conversion efficiency > 25 % in existing geometries.
      Finally, we present waveguide designs that can be used to connect shorter
      wavelength (637 nm to 852 nm) quantum emitters with 1550 nm.

PMID- 24104038
TI  - Accurate geometric characterization of gold nanorod ensemble by an inverse
      extinction/scattering spectroscopic method.
AB  - Aspect ratio, width, and end-cap factor are three critical parameters defined to
      characterize the geometry of metallic nanorod (NR). In our previous work [Opt.
      Express 21, 2987 (2013)], we reported an optical extinction spectroscopic (OES)
      method that can measure the aspect ratio distribution of gold NR ensembles
      effectively and statistically. However, the measurement accuracy was found to
      depend on the estimate of the width and end-cap factor of the nanorod, which
      unfortunately cannot be determined by the OES method itself. In this work, we
      propose to improve the accuracy of the OES method by applying an auxiliary
      scattering measurement of the NR ensemble which can help to estimate the mean
      width of the gold NRs effectively. This so-called optical extinction/scattering
      spectroscopic (OESS) method can fast characterize the aspect ratio distribution
      as well as the mean width of gold NR ensembles simultaneously. By comparing with
      the transmission electron microscopy experimentally, the OESS method shows the
      advantage of determining two of the three critical parameters of the NR ensembles
      (i.e., the aspect ratio and the mean width) more accurately and conveniently than
      the OES method. 

PMID- 24104039
TI  - Switching using PT symmetry in plasmonic systems: positive role of the losses.
AB  - We analyze the operation of 2 * 2 switches composed of two coupled waveguides
      operating on the basis of parity-time (PT) symmetry: the two waveguides differ
      through their gain or loss factors and not through the real part of their
      propagation constant. Plasmonics constitutes a preferred application for such
      systems, since combination of plasmonics with gain is increasingly mastered. The
      exact PT-symmetric case (gain and loss of identical absolute value) is considered
      as well as various unbalanced cases, thanks to their respective switching
      diagrams. Although perfect signal-conserving cross and bar states are not always
      possible in the latter cases, they can nevertheless form the basis of very good
      switches if precise design rules are followed. We draw from the analysis what the
      optimal configurations are in terms of, e.g., guide gain or gain-length product
      to operate the switch. Many analytical or semi-analytical results are pointed
      out. A practical example based on the coupling of a long-range surface-plasmon
      polariton and a polymeric waveguide having gain is provided. 

PMID- 24104040
TI  - Synchronized photonic modulators driven by surface acoustic waves.
AB  - Photonic modulators are one of the most important elements of integrated
      photonics. We have designed, fabricated, and characterized a tunable photonic
      modulator consisting of two 180 degrees -dephased output waveguide channels,
      driven by a surface acoustic wave in the GHz frequency range built on (Al,Ga)As.
      Odd multiples of the fundamental driven frequency are enabled by adjusting the
      applied acoustic power. A good agreement between theory and experimental results
      is achieved. The device can be used as a building block for more complex
      integrated functionalities and can be implemented in several material platforms. 

PMID- 24104041
TI  - Monolithic 626 nm single-mode AlGaInP DBR diode laser.
AB  - Single-mode lasers below 630 nm are still realized using complex laser systems.
      We present distributed Bragg reflector (DBR) ridge waveguide lasers (RWL) based
      on AlGaInP. When packaged into sealed TO-3 housings and cooled internally to
      about 0 degrees C the DBR-RWL emit more than 50 mW at a wavelength of 626.0 nm
      into a nearly diffraction-limited single longitudinal mode with a spectral width
      below 1 MHz. These new monolithic diode lasers have the potential to drastically
      miniaturize existing set-ups e.g. for quantum information processing. 

PMID- 24104042
TI  - Optimally shaped narrowband picosecond pulses for femtosecond stimulated Raman
      spectroscopy.
AB  - A comparison between a Fabry-Perot etalon filter and a conventional grating
      filter for producing the picosecond (ps) Raman pump pulses for femtosecond
      stimulated Raman spectroscopy (FSRS) is presented. It is shown that for pulses of
      equal energy the etalon filter produces Raman signals twice as large as that of
      the grating filter while suppressing the electronically resonant background
      signal. The time asymmetric profile of the etalon-generated pulse is shown to be
      responsible for both of these observations. A theoretical discussion is presented
      which quantitatively supports this hypothesis. It is concluded that etalons are
      the ideal method for the generation of narrowband ps pulses for FSRS because of
      the optical simplicity, efficiency, improved FSRS intensity and reduced
      backgrounds. 

PMID- 24104043
TI  - Adjoint shape optimization applied to electromagnetic design.
AB  - We present an adjoint-based optimization for electromagnetic design. It embeds
      commercial Maxwell solvers within a steepest-descent inverse-design optimization
      algorithm. The adjoint approach calculates shape derivatives at all points in
      space, but requires only two "forward" simulations. Geometrical shape
      parameterization is by the level set method. Our adjoint design optimization is
      applied to a Silicon photonics Y-junction splitter that had previously been
      investigated by stochastic methods. Owing to the speed of calculating shape
      derivatives within the adjoint method, convergence is much faster, within a
      larger design space. This is an extremely efficient method for the design of
      complex electromagnetic components. 

PMID- 24104044
TI  - Tunable microwave-photonic filter using frequency-to-time mapping-based delay
      lines.
AB  - A new implementation of microwave-photonic filters (MPFs) based on tunable
      optical delay lines is proposed and demonstrated. The variable delay is based on
      mapping of the spectral components of an incoming waveform onto the time domain,
      the application of linearly-varying temporal phase offsets, and an inverse
      mapping back to the frequency domain. The linear phase correction is equivalent
      to a frequency offset, and realized though suppressed-carrier single-sideband
      modulation by a radio-frequency sine wave. The variable delay element, controlled
      by the selected frequency, is used in one arm of a two-tap MPF. In a proof-of
      concept experiment, the free spectral range (FSR) of the MPF was varied by over a
      factor of four: between 1.2 GHz and 5.3 GHz. 

PMID- 24104045
TI  - Multi foci with diffraction limited resolution.
AB  - The generation of multi foci is an established method for high-speed parallel
      direct laser writing, scanning microscopy and for optical tweezer arrays.
      However, the quality of multi foci reduces with increasing resolution due to
      interference effects. Here, we report on a spatial-light-modulator-based method
      that allows for highly uniform, close to Gaussian spots with diffraction limited
      resolution using a wavelength of 780 nm. We introduce modifications of a standard
      algorithm that calculates a field distribution on the entrance pupil of a high
      numerical aperture objective splitting the focal volume into a multitude of
      spots. Our modified algorithm compares favourably to a commonly used algorithm in
      full vectorial calculations as well as in point-spread-function measurements. The
      lateral and axial resolution limits of spots generated by the new algorithm are
      found to be close to the diffraction limit. 

PMID- 24104046
TI  - A boracite metal-organic framework displaying selective gas sorption and guest
      dependent spin-crossover behaviour.
AB  - A metal-organic framework, [{Fe(NCS)2}3(TPB)4].x(guest) [.x(guest), TPB = 1,3,5
      tris(4-pyridyl)benzene], shows selective gas adsorption and guest-dependent spin
      crossover behaviour. 

PMID- 24104047
TI  - A patient with loin hematuria syndrome and chronic flank pain treated with pulsed
      radiofrequency of the splanchnic nerves.
AB  - INTRODUCTION: Chronic abdominal and flank pain can be multifactorial and
      difficult to treat. Loin pain hematuria syndrome (LPHS) is a rare clinical cause
      of chronic abdominal and flank pain and is a diagnosis of exclusion with limited
      treatment options, ranging from medications to renal autotransplantation or even
      nephrectomy in resistant cases. CASE DESCRIPTION: A 50-year-old man with a
      history of recurrent nephrolithiasis secondary to hypercalcemia presented to the
      pain clinic with bilateral flank pain. After failed conservative medical
      management, the decision was made to proceed to interventional modalities. He
      responded for a short duration to a splanchnic nerve block and subsequently had a
      longer analgesic response to pulsed radiofrequency (PRF) ablation to the
      splanchnic nerves. DISCUSSION: LPHS is a difficult clinical scenario to diagnose
      and treat. Conservative options are often unsuccessful, but the more extreme
      interventions such as renal autotransplantation and nephrectomies are invasive
      and not always effective. In this case report, we describe the novel use of PRF
      to the splanchnic nerves as an alternative treatment modality for patients with
      LPHS.Although the exact mechanism of action of PRF on nerve tissue is unclear,
      its indication in pain management requires further research and discussion. Our
      patient experienced substantial and sustained relief of his flank pain. PRF may
      be a viable option for patients with LPHS.

PMID- 24104048
TI  - Favorable outcome of an acute complex regional pain syndrome with immunoglobulin
      infusions.
AB  - OBJECTIVE: To emphasize that complex regional pain syndrome (CRPS), a disabling
      disorder with the implication of aberrant inflammation, vasomotor dysfunction,
      and maladaptive neuroplasticity, might be treated with a high dose of intravenous
      immunoglobulin infusions (IVIG). METHODS: We describe a patient who presented
      with CRPS in the acute phase of the disease. RESULTS: The CRPS developed
      secondary to sciatic compression in a young patient and was treated within 10
      days by high-dose IVIG (2 g/kg). It resolved completely within days after
      infusions. DISCUSSION: This observational study emphasizes that high-dose IVIG
      may be a treatment option in the acute phase of CRPS.

PMID- 24104050
TI  - An experimental study on the effects of peer drinking norms on adolescents'
      drinker prototypes.
AB  - BACKGROUND: Adolescents form impressions about the type of peers who drink (i.e.,
      drinker prototypes). The evaluation of, and perceived similarity to these
      prototypes are related to adolescents' drinking. Peer drinking norms play an
      important role in the formation of prototypes. We experimentally examined whether
      manipulation of peer norms changed the evaluation of and perceived similarity to
      drinker prototypes and whether these changes were moderated by peers' popularity.
      METHODS: In a pre-test, we assessed heavy drinker, moderate drinker and abstainer
      prototypes, drinking behaviors and peer-perceived popularity among 599
      adolescents. Additionally, 88 boys from this sample participated in a simulated
      chat room, in which they interacted with peers from school. These peers were in
      fact pre-programmed e-confederates, who were either popular or unpopular and who
      communicated either pro-alcohol or anti-alcohol norms. After the chat room
      interaction we assessed participants' drinker prototypes. RESULTS: Participants
      exposed to anti-alcohol norms were more negative about, and perceived themselves
      as less similar to heavy drinker prototypes, than participants exposed to pro
      alcohol norms. We found no effects of peer norms on moderate drinker and
      abstainer prototypes. Effects were not moderated by peers' popularity. We did
      find a main effect of popularity on perceived similarity to all prototypes. This
      indicated that participants rated themselves as more similar to heavy and
      moderate drinker prototypes and less similar to abstainer prototypes when they
      interacted with unpopular peers than with popular peers. CONCLUSIONS: Exposure to
      anti-alcohol norms of peers leads adolescents to form more negative prototypes of
      the heavy drinker. This could be an important finding for prevention and
      intervention programs aimed to reduce alcohol consumption among adolescents.

PMID- 24104049
TI  - Psychological and neural mechanisms of experimental extinction: a selective
      review.
AB  - The present review examines key psychological concepts in the study of
      experimental extinction and implications these have for an understanding of the
      underlying neurobiology of extinction learning. We suggest that many of the
      signature characteristics of extinction learning (spontaneous recovery, renewal,
      reinstatement, rapid reacquisition) can be accommodated by the standard
      associative learning theory assumption that extinction results in partial erasure
      of the original learning together with new inhibitory learning. Moreover, we
      consider recent behavioral and neural evidence that supports the partial erasure
      view of extinction, but also note shortcomings in our understanding of extinction
      circuits as these relate to the negative prediction error concept. Recent work
      suggests that common prediction error and stimulus-specific prediction error
      terms both may be required to explain neural plasticity both in acquisition and
      extinction learning. In addition, we suggest that many issues in the content of
      extinction learning have not been fully addressed in current research, but that
      neurobiological approaches should be especially helpful in addressing such
      issues. These include questions about the nature of extinction learning
      (excitatory CS-No US, inhibitory CS-US learning, occasion setting processes),
      especially as this relates to studies of the micro-circuitry of extinction, as
      well as its representational content (sensory, motivational, response). An
      additional understudied problem in extinction research is the role played by
      attention processes and their underlying neural networks, although some research
      and theory converge on the idea that extinction is accompanied by attention
      decrements (i.e., habituation-like processes). 

PMID- 24104051
TI  - Fructan metabolism in developing wheat (Triticum aestivum L.) kernels.
AB  - Although fructans play a crucial role in wheat kernel development, their
      metabolism during kernel maturation is far from being understood. In this study,
      all major fructan-metabolizing enzymes together with fructan content, fructan
      degree of polymerization and the presence of fructan oligosaccharides were
      examined in developing wheat kernels (Triticum aestivum L. var. Homeros) from
      anthesis until maturity. Fructan accumulation occurred mainly in the first 2
      weeks after anthesis, and a maximal fructan concentration of 2.5 +/- 0.3 mg
      fructan per kernel was reached at 16 days after anthesis (DAA). Fructan synthesis
      was catalyzed by 1-SST (sucrose:sucrose 1-fructosyltransferase) and 6-SFT
      (sucrose:fructan 6-fructosyltransferase), and to a lesser extent by 1-FFT
      (fructan:fructan 1-fructosyltransferase). Despite the presence of 6G-kestotriose
      in wheat kernel extracts, the measured 6G-FFT (fructan:fructan 6G
      fructosyltransferase) activity levels were low. During kernel filling, which
      lasted from 2 to 6 weeks after anthesis, kernel fructan content decreased from
      2.5 +/- 0.3 to 1.31 +/- 0.12 mg fructan per kernel (42 DAA) and the average
      fructan degree of polymerization decreased from 7.3 +/- 0.4 (14 DAA) to 4.4 +/-
      0.1 (42 DAA). FEH (fructan exohydrolase) reached maximal activity between 20 and
      28 DAA. No fructan-metabolizing enzyme activities were registered during the
      final phase of kernel maturation, and fructan content and structure remained
      unchanged. This study provides insight into the complex metabolism of fructans
      during wheat kernel development and relates fructan turnover to the general
      phases of kernel development.

PMID- 24104052
TI  - New approaches to the biology of stomatal guard cells.
AB  - CO2 acts as an environmental signal that regulates stomatal movements. High CO2
      concentrations reduce stomatal aperture, whereas low concentrations trigger
      stomatal opening. In contrast to our advanced understanding of light and drought
      stress responses in guard cells, the molecular mechanisms underlying stomatal CO2
      sensing and signaling are largely unknown. Leaf temperature provides a convenient
      indicator of transpiration, and can be used to detect mutants with altered
      stomatal control. To identify genes that function in CO2 responses in guard
      cells, CO2-insensitive mutants were isolated through high-throughput leaf thermal
      imaging. The isolated mutants are categorized into three groups according to
      their phenotypes: (i) impaired in stomatal opening under low CO2 concentrations;
      (ii) impaired in stomatal closing under high CO2 concentrations; and (iii)
      impaired in stomatal development. Characterization of these mutants has begun to
      yield insights into the mechanisms of stomatal CO2 responses. In this review, we
      summarize the current status of the field and discuss future prospects. 

PMID- 24104054
TI  - [Causes and pathogenesis of noma in Zinder (Niger): a socio-anthropological
      study].
AB  - OBJECTIVES: Noma is a gangrenous affliction that destroys the soft and hard
      tissue of the face. It affects exclusively young children from developing
      countries. Although the risk factors (malnutrition and debilitating diseases) are
      known, the cause remains a topic of debate. Etiological studies have tried to
      identify bacterial or viral agents responsible for the illness. We examine for
      the first time the possibility of a link between this illness and the social
      practices surrounding childbirth. METHODS: This study took place in Niger, where
      we conducted 18 ethnographic interviews with mothers from four villages. Noma was
      known in two villages, but unknown in the other two. RESULTS: Our results show
      that inadequate practices related to breastfeeding, weaning, and nutritional
      supplementation practices are by themselves insufficient to initiate the disease,
      insofar as most of these practices, paradoxically, were found in the villages not
      affected by the disease. CONCLUSION: The results indicate that these practices
      are not sufficient to explain noma. They suggest, however, that poor maternal
      health and nutritional status before and during pregnancy may have an
      irreversible negative impact on the child's overall health.

PMID- 24104055
TI  - Does liking or wanting determine repeat consumption delay?
AB  - Does liking or wanting predict the delay between consumption episodes? Although
      these psychological processes are correlated, we find that memory for liking,
      rather than wanting, determines the number of days that pass until the
      consumption of a food is repeated. Experiment 1 found that liking (but not
      wanting) for a food at the end of a consumption experience predicted how many
      days passed until participants wanted to consume it again. Experiment 2 showed
      that mitigating the decrease in liking resulting from the repeated consumption of
      a food eliminates its effect on delay. Together, these findings suggest that end
      liking has a greater influence on when people will consume a food again in the
      future. 

PMID- 24104053
TI  - Transport of the influenza virus genome from nucleus to nucleus.
AB  - The segmented genome of an influenza virus is encapsidated into ribonucleoprotein
      complexes (RNPs). Unusually among RNA viruses, influenza viruses replicate in the
      nucleus of an infected cell, and their RNPs must therefore recruit host factors
      to ensure transport across a number of cellular compartments during the course of
      an infection. Recent studies have shed new light on many of these processes,
      including the regulation of nuclear export, genome packaging, mechanisms of
      virion assembly and viral entry and, in particular, the identification of Rab11
      on recycling endosomes as a key mediator of RNP transport and genome assembly.
      This review uses these recent gains in understanding to describe in detail the
      journey of an influenza A virus RNP from its synthesis in the nucleus through to
      its entry into the nucleus of a new host cell. 

PMID- 24104057
TI  - Secondary diphosphine and diphosphido ligands: synthesis, characterisation and
      group 1 coordination compounds.
AB  - Two types of secondary diphosphines, 1,8-(ArPH)2C14H8 (1a: Ar = Tripp, 2,4,6
      triisopropylphenyl; 1b: Ar = Mes, 2,4,6-trimethylphenyl) and 1,3
      ((t)BuPHCH2)2C6H4 (2), based on rigid 1,8-anthracene and flexible m-xylyl
      frameworks, respectively, have been synthesized using different strategies.
      Compounds 1a and 1b were formed by nucleophilic aromatic substitution of a
      potassium organophosphido salt onto 1,8-difluoroanthracene, while compound 2 was
      obtained by addition of the Grignard reagent [1,3-(ClMgCH2)2C6H4]x to a
      dichloroorganophosphine, followed by reduction to the diphosphine. These
      compounds were isolated as ca. 1 : 1 mixtures of rac and meso diastereomers as
      determined by multinuclear NMR spectroscopy. Borane and selenide derivatives of
      2, 1,3-((t)BuPH(BH3)CH2)2C6H4 (3) and 1,3-((t)BuPH(Se)CH2)2C6H4 (4), were
      obtained. Preferential crystallization of one diastereomer of 3 and 4 was
      observed; X-ray crystallographic studies identified this as the rac isomer for
      diselenide 4. Metallation studies of compounds 1a and 2 yielded several alkali
      metal salts. The reaction of KH or K metal with 1a yielded the compounds 1,8
      (TrippPK)2C14H8.xTHF (5) and 1,8-(TrippPK)2C14H10.xTHF (6), respectively; in
      complex 6 the central aromatic ring has been reduced to yield a bent
      dihydroanthracene backbone. A crown ether derivative of 6, [K(18-crown
      6)(THF)2]2[1,8-(TrippP)2C14H10] (7), was characterised crystallographically.
      Double deprotonation of compound 2 with (n)BuLi/TMEDA (TMEDA = N,N,N',N'
      tetramethylethylenediamine) afforded the yellow dilithium complex 1,3
      ((t)BuPLiCH2)2C6H4.TMEDA (8), which crystallized as a dimer featuring lithium
      arene pi interactions.

PMID- 24104058
TI  - RETRACTED: Auricular prosthesis fabrication using computer-aided design and rapid
      prototyping technologies.
AB  - At the request of the editorMayank Shah 'Auricular prosthesis fabrication using
      computer-aided design and rapid prototyping technologies' Prosthetics and
      Orthotics International, published online before print on October 8, 2013 as
      doi:10.1177/0309364613504779has been retracted. This is because it contains
      unattributed overlap withK. Subburaj, C. Nair, S. Rajesh, S. M. Meshram, B. Ravi
      'Rapid development of auricular prosthesis using CAD and rapid prototyping
      technologies' International Journal of Oral & Maxillofacial Surgery 2007; 36: 938
      943 doi:10.1016/j.ijom.2007.07.013.

PMID- 24104056
TI  - Rabaptin-5 and Rabex-5 are neoplastic tumour suppressor genes that interact to
      modulate Rab5 dynamics in Drosophila melanogaster.
AB  - Endocytosis plays an important role in the regulation of tumour growth and
      metastasis. In Drosophila, a number of endocytic neoplastic tumour suppressor
      genes have been identified that when mutated cause epithelial disruption and over
      proliferation. Here we characterise the Drosophila homologue of the Rab5 effector
      Rabaptin-5, and show that it is a novel neoplastic tumour suppressor. Its ability
      to bind Rab5 and modulate early endosomal dynamics is conserved in Drosophila, as
      is its interaction with the Rab5 GEF Rabex5, for which we also demonstrate
      neoplastic tumour suppressor characteristics. Surprisingly, we do not observe
      disruption of apico-basal polarity in Rabaptin-5 and Rabex-5 mutant tissues;
      instead the tumour phenotype is associated with upregulation of Jun N-terminal
      Kinase (JNK) and Janus Kinase (JAK)/Signal Transducer and Activator of
      Transcription (STAT) signalling. 

PMID- 24104059
TI  - Inter-dependent tissue growth and Turing patterning in a model for long bone
      development.
AB  - The development of long bones requires a sophisticated spatial organization of
      cellular signalling, proliferation, and differentiation programs. How such
      spatial organization emerges on the growing long bone domain is still unresolved.
      Based on the reported biochemical interactions we developed a regulatory model
      for the core signalling factors IHH, PTCH1, and PTHrP and included two cell
      types, proliferating/resting chondrocytes and (pre-)hypertrophic chondrocytes. We
      show that the reported IHH-PTCH1 interaction gives rise to a Schnakenberg-type
      Turing kinetics, and that inclusion of PTHrP is important to achieve robust
      patterning when coupling patterning and tissue dynamics. The model reproduces
      relevant spatiotemporal gene expression patterns, as well as a number of relevant
      mutant phenotypes. In summary, we propose that a ligand-receptor based Turing
      mechanism may control the emergence of patterns during long bone development,
      with PTHrP as an important mediator to confer patterning robustness when the
      sensitive Turing system is coupled to the dynamics of a growing and
      differentiating tissue. We have previously shown that ligand-receptor based
      Turing mechanisms can also result from BMP-receptor, SHH-receptor, and GDNF
      receptor interactions, and that these reproduce the wildtype and mutant patterns
      during digit formation in limbs and branching morphogenesis in lung and kidneys.
      Receptor-ligand interactions may thus constitute a general mechanism to generate
      Turing patterns in nature. 

PMID- 24104060
TI  - Review of 10 years of clinical experience with Chinese domestic trivalent
      influenza vaccine Anflu(r).
AB  - Influenza viruses cause annual winter epidemics globally and influenza
      vaccination is most effective way to prevent the disease or severe outcomes from
      the illness, especially in developing countries. However, the majority of the
      world's total production capacity of influenza vaccine is concentrated in several
      large multinational manufacturers. A safe and effective preventive vaccine for
      the developing countries is urgent. Anflu(r), a Chinese domestic preservative
      free, split-virus trivalent influenza vaccine (TIV), was introduced by Sinovac
      Biotech Ltd. in 2006. Until now, 20.6 million doses worldwide of Anflu(r) were
      sold. Since 2003, 13 company-sponsored clinical studies investigating the
      immunogenicity and safety of Anflu(r) have been completed, in which 6642 subjects
      participated and were vaccinated by Anflu(r). Anflu(r) was generally well
      tolerated in all age groups, and highly immunogenic in healthy adults and elderly
      and exceeded the licensure criteria in Europe. This review presents and discusses
      the experience with Anflu(r) during the past decade. A new Chinese domestic,
      preservative-free, unadjuvanted, inactivated split-virus trivalent influenza
      vaccine (TIV), Anflu(r), was introduced into human clinical trials in 2003 and
      then licensed in China in 2006. The vaccine contains 15 ug/0.5 ml hemagglutinin
      from each of the 3 influenza virus strains (including an H1N1 influenza A virus
      subtype, an H3N2 influenza A virus subtype, and an influenza B virus) that are
      expected to be circulating in the up-coming influenza season. The clinical data
      pertaining to Anflu(r) will be reviewed and compared with other TIVs available at
      present.

PMID- 24104061
TI  - Permethrin exposure from fabric-treated military uniforms under different wear
      time scenarios.
AB  - The objective of the project was to ascertain whether urinary biomarkers of
      permethrin exposure are detected after wearing post-tailored, fabric-treated
      military uniforms under two different wear-time exposure scenarios. Study A
      occurred over 3.5 days and involved six participants wearing treated uniforms
      continuously for 30-32 h. Urine collection occurred at scheduled time points
      before, during, and after wearing the uniform. Study B, conducted over 19 days,
      included 11 participants wearing treated uniforms for 3 consecutive days, 8 h
      each day (with urine collection before, during, and after wear). Urinary
      biomarkers of permethrin (3-phenoxybenzoic acid (3PBA), cis- 2,2-(dichlorovinyl)
      2,2-dimethylcyclopropane-1-carboxylic acid (cDCCA), trans- 2,2-(dichlorovinyl)
      2,2-dimethylcyclopropane-1-carboxylic acid (tDCCA)) were detected during and
      after wear. Biomarker detection generally occurred over the 10- to 12-h period
      after putting on the uniform and subsided 24 h following uniform removal (in both
      Study A and B scenarios). Those wearing permethrin-treated uniforms under the
      longer wear-time scenario (Study A) excreted significantly higher cumulative mean
      levels compared with those in Study B (3.29 times higher for 3PBA and 2.23 times
      higher for the sum of c/tDCCA (P<=0.001)). Findings suggest that wearing
      permethrin-treated clothing does increase absorbed, internal dose levels of
      permethrin above population levels and is significantly related to wear-time
      duration.

PMID- 24104064
TI  - Synthesis of 2,3-butanediol by Synechocystis sp. PCC6803 via heterologous
      expression of a catabolic pathway from lactic acid- and enterobacteria.
AB  - The direct and efficient conversion of CO2 into liquid energy carriers and/or
      bulk chemicals is crucial for a sustainable future of modern society. Here we
      describe the production of 2,3-butanediol in Synechocystis sp. PCC6803 expressing
      a heterologous catabolic pathway derived from enteric- and lactic acid bacteria.
      This pathway is composed of an acetolactate synthase, an acetolactate
      decarboxylase and an acetoin reductase. Levels of up to 0.72 g/l (corresponding
      to 8 mmol/L) of C(4) products, including a level of 0.43 g/l (corresponding to
      4.7 mmol/L) 2,3-butanediol production are observed with the genes encoding these
      three enzymes integrated into the cyanobacterial genome, as well as when they are
      plasmid encoded. Further optimization studies revealed that Synechocystis
      expresses significant levels of acetolactate synthase endogenously, particularly
      under conditions of restricted CO2 supply to the cells. Co-expression of a
      soluble transhydrogenase or of an NADPH-dependent acetoin reductase allows one to
      drive the last step of the engineered pathway to near completion, resulting in
      pure meso-2,3-butanediol being produced.

PMID- 24104065
TI  - Cognitive processing speed has minimal influence on the construct validity of
      Multiple Sclerosis Walking Scale-12 scores.
AB  - BACKGROUND: The Multiple Sclerosis Walking Scale-12 (MSWS-12) has been a commonly
      used patient reported outcome for measuring walking impairment in research
      involving multiple sclerosis (MS). OBJECTIVE: We examined the possibility that
      cognitive processing speed (CPS) influences the association between MSWS-12
      scores and other measures of ambulation (i.e., construct validity). METHODS: 96
      MS patients completed the MSWS-12, underwent a neurological examination for
      generating an Expanded Disability Status Scale (EDSS) score, and completed the
      Symbol Digit Modalities Test (SDMT), Timed 25-Foot Walk (T25FW), 4 trials on the
      GAITRiteTM for generating the functional ambulatory profile (FAP) score, and Six
      minute Walk (6MW). RESULTS: The SDMT was significantly correlated with MSWS-12
      scores (r=-.428) and T25FW (r=-.459), 6MW (r=.512), FAP (r=.275), and EDSS (r=
      .404) scores. There were statistically significant correlations between MSWS-12
      and T25FW (r=.568), 6MW (r=-.680), FAP (r=-.595), and EDSS (r=.737) scores.
      Lastly, four separate hierarchical linear regression analyses indicated that,
      after controlling for age, gender, disease duration, and clinical course, T25FW,
      6MW, FAP, and EDSS scores individually were significant correlates of MSWS-12
      scores, and the associations (i.e., standardized beta-coefficients) were still
      statistically significant with minimal attenuation when controlling for SDMT
      scores. CONCLUSION: There was minimal evidence that CPS influenced the construct
      validity of MSWS-12 scores.

PMID- 24104066
TI  - Homogenization of three-dimensional metamaterial objects and validation by a fast
      surface-integral equation solver.
AB  - A homogenization model is applied to describe the wave interaction with finite
      three-dimensional metamaterial objects composed of periodic arrays of
      magnetodielectric spheres and is validated with full-wave numerical simulations.
      The homogenization is based on a dipolar model of the inclusions, which is shown
      to hold even in the case of densely packed arrays once weak forms of spatial
      dispersion and the full dynamic array coupling are taken into account. The
      numerical simulations are based on a fast surface-integral equation solver that
      enables the analysis of scattering from complex piecewise homogeneous objects. We
      validate the homogenization model by considering electrically large disk- and
      cube-shaped arrays and quantify the accuracy of the transition from an array of
      spheres to a homogeneous object as a function of the array size. Simulation
      results show that the fields scattered from large arrays with up to one thousand
      spheres and equivalent homogeneous objects agree well, not only far away from the
      arrays but also near them. 

PMID- 24104067
TI  - Aperiodic CrSc multilayer mirrors for attosecond water window pulses.
AB  - Extending single attosecond pulse technology from currently sub-200 eV to the so
      called 'water window' spectral range may enable for the first time the unique
      investigation of ultrafast electronic processes within the core states of bio
      molecules as proteins or other organic materials. Aperiodic multilayer mirrors
      serve as key components to shape these attosecond pulses with a high degree of
      freedom and enable tailored short pulse pump-probe experiments. Here, we report
      on chirped CrSc multilayer mirrors, fabricated by ion beam deposition with sub
      angstrom precision, designed for attosecond pulse shaping in the 'water window'
      spectral range. 

PMID- 24104068
TI  - Coupled mode enhanced giant magnetoplasmonics transverse Kerr effect.
AB  - We show that the enhancement of the transverse magneto-optical Kerr effect of a
      smooth magnetic dielectric film covered by a noble metal grating, is strongly
      dependent on the precise geometry of this grating. Up till now this
      magnetoplasmonic enhancement was solely attributed to a nonreciprocal shift of
      the dispersion of the surface plasmon polariton resonances at the interface with
      the magnetized substrate. It is demonstrated that by hybridization of surface and
      cavity resonances in this 1D plasmonic grating, the transverse Kerr effect can be
      further enhanced, extinguished or even switched in sign and that without
      inverting or modifying the film's magnetization. This strong geometrical
      dispersion and the accompanying anomalous sign change of the magneto-plasmonic
      effects in such systems has never been considered before, and might find
      interesting applications in sensing and nanophotonics.

PMID- 24104062
TI  - Hypoxia induces phenotypic plasticity and therapy resistance in melanoma via the
      tyrosine kinase receptors ROR1 and ROR2.
AB  - An emerging concept in melanoma biology is that of dynamic, adaptive phenotype
      switching, where cells switch from a highly proliferative, poorly invasive
      phenotype to a highly invasive, less proliferative one. This switch may hold
      significant implications not just for metastasis, but also for therapy
      resistance. We demonstrate that phenotype switching and subsequent resistance can
      be guided by changes in expression of receptors involved in the noncanonical
      Wnt5A signaling pathway, ROR1 and ROR2. ROR1 and ROR2 are inversely expressed in
      melanomas and negatively regulate each other. Furthermore, hypoxia initiates a
      shift of ROR1-positive melanomas to a more invasive, ROR2-positive phenotype.
      Notably, this receptor switch induces a 10-fold decrease in sensitivity to BRAF
      inhibitors. In patients with melanoma treated with the BRAF inhibitor
      vemurafenib, Wnt5A expression correlates with clinical response and therapy
      resistance. These data highlight the fact that mechanisms that guide metastatic
      progression may be linked to those that mediate therapy resistance. SIGNIFICANCE:
      These data show for the fi rst time that a single signaling pathway, the Wnt
      signaling pathway, can effectively guide the phenotypic plasticity of tumor
      cells, when primed to do so by a hypoxic microenvironment. Importantly, this
      increased Wnt5A signaling can give rise to a subpopulation of highly invasive
      cells that are intrinsically less sensitive to novel therapies for melanoma, and
      targeting the Wnt5A/ROR2 axis could improve the efficacy and duration of response
      for patients with melanoma on vemurafenib.

PMID- 24104069
TI  - A carrier removal method in phase measuring deflectometry based on the analytical
      carrier phase description.
AB  - In phase measuring deflectometry (PMD), a camera observes a sinusoidal fringe
      pattern via the surface of a specular object under test. Any slope variations of
      the surface lead to distortions of the observed pattern. Without height-angle
      ambiguity, carrier removal process is adopted to evaluate the variation of
      surface slope from phase distribution when a quasi-plane is measured. However, in
      the usual measurement system, the carrier phase will be nonlinear due to the
      restrictions of system geometries. In this paper, based on the analytical carrier
      phase description in PMD, a carrier removal method is proposed to remove the
      nonlinear carrier phase. Both the theoretical analysis and the experiment results
      are presented. By comparison with reference-subtraction method and series
      expansion method, this proposed method can achieve carrier removal process with
      only the measurement of one single object, as well as high accuracy and time
      saving. 

PMID- 24104070
TI  - Blind channel estimation for MLSE receiver in high speed optical communications:
      theory and ASIC implementation.
AB  - Blind channel estimation is critical for digital signal processing (DSP)
      compensation of optical fiber communications links. The overall channel consists
      of deterministic distortions such as chromatic dispersion, as well as random and
      time varying distortions including polarization mode dispersion and timing
      jitter. It is critical to obtain robust acquisition and tracking methods for
      estimating these distortions effects, which, in turn, can be compensated by means
      of DSP such as Maximum Likelihood Sequence Estimation (MLSE). Here, a novel blind
      estimation algorithm is developed, accompanied by inclusive mathematical
      modeling, and followed by extensive set of real time experiments that verify
      quantitatively its performance and convergence. The developed blind channel
      estimation is used as the basis of an MLSE receiver. The entire scheme is fully
      implemented in a 65 nm CMOS Application Specific Integrated Circuit (ASIC).
      Experimental measurements and results are presented, including Bit Error Rate
      (BER) measurements, which demonstrate the successful data recovery by the MLSE
      ASIC under various channel conditions and distances.

PMID- 24104071
TI  - Photorefractive inhibition of second harmonic generation in periodically poled
      MgO doped LiNbO3 waveguide.
AB  - The inhibition of high power second-harmonic generation (SHG) in a periodically
      poled MgO doped LiNbO3 (PPMgLN) waveguide operating at near the room temperature
      has been interpreted by systematically investigating the SHG process based on the
      coupled mode equations in combination with the photorefraction and the
      temperature nonuniformities. The simulation results show that significant
      refractive index nonuniformities are induced by the photorefractive effect along
      the irradiated zone while those induced by the thermal effect are very minor.
      Therefore, the photorefractive effect instead of the thermal effect is the main
      factor that inhibits the SHG conversion efficiency. In addition, comparison of
      PPMgLN waveguides with different transverse dimensions shows that the waveguides
      with larger transverse dimension is advantageous in high power SHG since the
      photorefractive effect is weaker.

PMID- 24104072
TI  - Origin of Bragg reflection peaks splitting in gratings fabricated using a
      multiple order phase mask.
AB  - We have studied the effect of waveguide alignment on the reflection spectrum of
      Bragg gratings fabricated using a multiple order phase mask. We have demonstrated
      that splitting of certain Bragg peaks observed in earlier experiments reported in
      literature is caused by formation of the gratings with different periodicities in
      the waveguide tilted with respect to the phase mask plane due to the interference
      of non-symmetrical diffraction orders. Analytical expressions for spectral
      separation of the split peaks have been derived and verified against the
      experimental data recently presented in literature. The analytical predictions
      were also confirmed by numerical simulations of intensity distributions behind
      the multiple order diffraction grating and its projection on the tilted
      waveguide. 

PMID- 24104073
TI  - Occlusion culling for computer generated hologram based on ray-wavefront
      conversion.
AB  - We propose a new method for occlusion culling in the computation of a hologram
      based on the mutual conversion between light-rays and wavefront. Since the
      occlusion culling is performed with light-ray information, conventional rendering
      techniques such as ray-tracing or image-based rendering can be employed. On the
      other hand, the wavefront is derived for the calculation of light propagation,
      the hologram of 3-D objects can be obtained in high accuracy. In the numerical
      experiment, we demonstrate that our approach can reproduce a high-resolution
      image for deep 3-D scene with correct occlusion effect between plural objects. 

PMID- 24104074
TI  - Picosecond pulsed laser induced optical dichroism in glass with embedded metallic
      nanoparticles.
AB  - Picosecond (~10 ps) pulsed laser irradiation at 532 nm led to the efficient and
      scalable fabrication of dichroic areas in glass with spherical silver
      nanoparticles of ~30 - 40 nm in diameter embedded in a surface layer of thickness
      ~20 MUm. The observed dichroism is due to the uniform and permanent shape
      transformation of the nanoparticles - from spherical to spheroidal shapes -
      throughout the irradiated areas and along the laser polarization direction,
      paving the way for affordable manufacture of polarization-selective diffractive
      optical elements. The shape modification threshold and the dichroism as a result
      of Surface Plasmon Resonance band separation were identified. The process was
      then studied as a function of the laser polarization, repetition rate and the
      number of pulses fired per spot.

PMID- 24104075
TI  - MEMS Fabry-Perot sensor interrogated by optical system-on-a-chip for simultaneous
      pressure and temperature sensing.
AB  - We present a micro-electro-mechanical systems (MEMS) based Fabry-Perot (FP)
      sensor along with an optical system-on-a-chip (SOC) interrogator for simultaneous
      pressure and temperature sensing. The sensor employs a simple structure with an
      air-backed silicon membrane cross-axially bonded to a 45 degrees  polished
      optical fiber. This structure renders two cascaded FP cavities, enabling
      simultaneous pressure and temperature sensing in close proximity along the
      optical axis. The optical SOC consists of a broadband source, a MEMS FP tunable
      filter, a photodetector, and the supporting circuitry, serving as a miniature
      spectrometer for retrieving the two FP cavity lengths. Within the measured
      pressure and temperature ranges, experimental results demonstrate that the sensor
      exhibits a good linear response to external pressure and temperature changes.

PMID- 24104076
TI  - Direct optical switching of bistable cholesteric textures in chiral azobenzene
      doped liquid crystals.
AB  - The direct optical switching of bistable cholesteric textures (i.e., planar and
      focal conic textures) in chiral azobenzene-doped liquid crystals (LCs) is
      demonstrated. Chiral azobenzene is a chiral dopant with optically tuned helical
      twisting power that results from the photo-isomerization between trans- and cis-
      isomers via exposure to UV or visible light. The pitch length of the material can
      be optically and repeatedly elongated and shortened. With regard to free energy,
      LCs tend to be stable at planar (focal conic) textures when pitch length is
      elongated (shortened) by exposure to UV (visible) light. Thus, direct optical
      switchable LC displays are investigated. 

PMID- 24104077
TI  - Frequency resolved transverse mode instability in rod fiber amplifiers.
AB  - Frequency dynamics of transverse mode instabilities (TMIs) are investigated by
      testing three 285/100 rod fibers in a single-pass amplifier setup reaching up to
      ~200W of extracted output power without beam instabilities. The pump power is
      increased well above the TMI threshold to uncover output dynamics, and allowing a
      simple method for determining TMI threshold based on standard deviation. The TMI
      frequency component is seen to appear on top of system noise that may trigger the
      onset. A decay of TMI threshold with test number is identified, but the threshold
      is fully recovered between testing to the level of the pristine fiber by thermal
      annealing the fiber output end to 300 degrees C for 2 h.

PMID- 24104078
TI  - Optical near-field-mediated polarization asymmetry induced by two-layer
      nanostructures.
AB  - We demonstrate that a two-layer shape-engineered nanostructure exhibits
      asymmetric polarization conversion efficiency thanks to near-field interactions.
      We present a rigorous theoretical foundation based on an angular-spectrum
      representation of optical near-fields that takes account of the geometrical
      features of the proposed device architecture and gives results that agree well
      with electromagnetic numerical simulations. The principle used here exploits the
      unique intrinsic optical near-field processes associated with nanostructured
      matter, while eliminating the need for conventional scanning optical fiber
      probing tips, paving the way to novel nanophotonic devices and systems.

PMID- 24104079
TI  - Coupling of air/metal and substrate/metal surface plasmon polaritons in Au slit
      arrays fabricated on quartz substrate.
AB  - We report on the coupling of the air/metal mode and the substrate/metal mode
      surface plasmon polaritons in one-dimensional metallic slit arrays fabricated on
      a dielectric substrate. Anti-crossing is exhibited at an incident angle where the
      two independent modes can be resonantly excited at a specific wavelength. The
      size of the anti-crossing gap was measured while changing the metal thickness. 

PMID- 24104080
TI  - Analysis of rainbow scattering by a chiral sphere.
AB  - Based on the scattering theory of a chiral sphere, rainbow phenomenon of a chiral
      sphere is numerically analyzed in this paper. For chiral spheres illuminated by a
      linearly polarized wave, there are three first-order rainbows, with whose rainbow
      angles varying with the chirality parameter. The spectrum of each rainbow
      structure is presented and the ripple frequencies are found associated with the
      size and refractive indices of the chiral sphere. Only two rainbow structures
      remain when the chiral sphere is illuminated by a circularly polarized plane
      wave. Finally, the rainbows of chiral spheres with slight chirality parameters
      are found appearing alternately in E-plane and H-plane with the variation of the
      chirality.

PMID- 24104081
TI  - Pulse shaping with birefringent crystals: a tool for quantum metrology.
AB  - A method for time differentiation based on a Babinet-Soleil-Bravais compensator
      is introduced. The complex transfer function of the device is measured using
      polarization spectral interferometry. Time differentiation of both the pulse
      field and pulse envelope are demonstrated over a spectral width of about 100 THz
      with a measured overlap with the objective mode greater than 99.8%. This pulse
      shaping technique is shown to be perfectly suited to time metrology at the
      quantum limit.

PMID- 24104082
TI  - A flatbed scanner for large-area thickness determination of ultra-thin layers in
      printed electronics.
AB  - Enabling solution-based printing techniques for sub-100 nm thin semiconductors
      for the application in large-area organic electronics is a challenging task. In
      order to optimize the process parameters, the layers have to be characterized on
      a large lateral scale while determining the nanometer thickness at the same time.
      We present a lateral and vertical resolving measurement method for large-area,
      semi-transparent thin films based on optical interference effects. We analyzed
      the RGB color images of up to 150 mm square-sized thin film samples obtained by a
      modified commercial flatbed scanner. Utilizing and comparing theoretical and
      measured color contrast values, we determined most probable thickness values of
      the imaged sample area pixel by pixel. Within specific boundary conditions, we
      found very good agreement between the presented imaging color reflectometry and
      reference methods. Due to its simple setup, our method is suitable to be
      implemented as part of a color vision inspection system in in-line printing and
      coating processes.

PMID- 24104083
TI  - Effect of core boundary curvature on the confinement losses of hollow
      antiresonant fibers.
AB  - We use numerical simulations to investigate how the curvature of the fiber core
      boundary influences the attenuation of hollow antiresonant fibers. We show the
      importance of a "negative" curvature core boundary in reducing confinement losses
      and also how, for certain curvatures, optical power is coupled resonantly to
      cladding modes. We simulate bending losses and find results in agreement with
      previously-reported experiments.

PMID- 24104084
TI  - Third- and second-harmonic generation microscopy of individual metal nanocones
      using cylindrical vector beams.
AB  - We demonstrate third- (THG) and second-harmonic generation (SHG) microscopy of
      individual silver nanocones using tightly focused cylindrical vector beams
      (CVBs). Although THG is expected to be a weaker process than SHG, the yield for
      THG with radial polarization was higher than for SHG. We also found an excellent
      correlation between the imaging properties of THG and SHG, suggesting that both
      are governed by the same overall features of the individual nanocone. We also
      found that the transverse spatial resolution of THG with CVBs, particularly RP,
      exceeds that of SHG. Our work establishes the potential of THG microscopy with
      CVBs for structure-sensitive imaging of three-dimensional (3D) metal nano
      objects.

PMID- 24104085
TI  - Experimental demonstration of 110-Gb/s unsynchronized band-multiplexed
      superchannel coherent optical OFDM/OQAM system.
AB  - In this paper, we experimentally demonstrate the first 110-Gb/s multi-band
      superchannel coherent optical orthogonal frequency-division multiplexing based on
      offset quadrature amplitude modulation (OFDM/OQAM) system. Unlike the
      conventional orthogonal band-multiplexed OFDM system, no timing or frequency
      synchronization is required for the OFDM/OQAM system. We further investigate the
      influence of guard band, and find that very trivial guard band spacing (< 20 MHz)
      is required without any sensitivity performance or spectral efficiency
      degradation. Thus, the newly designed scheme would significantly reduce the
      implementation constrains for the band-multiplexed superchannel coherent optical
      OFDM system.

PMID- 24104086
TI  - Performance investigation of a hybrid fiber optical parametric amplifier.
AB  - We demonstrate reduction of four-wave mixing crosstalk using hybrid optical
      parametric amplifier with erbium-doped fiber amplifier. Crosstalk reduction of
      more than 13 dB has been achieved while providing 20-dB gain. Noise figures of
      different amplifier configurations are compared. Bit error rate measurements
      confirm the hybrid configuration introduces < 0.5 dB and < 1.5 dB power penalties
      in signal and idler wavelength, respectively, compared with a pure optical
      parametric amplifier.

PMID- 24104087
TI  - Homogenization of bi-anisotropic metasurfaces.
AB  - Ultrathin metamaterial layers are modeled by a homogeneous bi-anisotropic film to
      represent various kinds of broken symmetries in photonic nanostructures, and
      specifically in optical metamaterials and metasurfaces. Two algorithms were
      developed to obtain the electromagnetic (EM) wave response from a metasurface
      (direct solver) or the metasurface parameters from the EM wave response (inverse
      solver) for a bi-anisotropic, subwavelength-thick nanostructured film. The
      algorithm is applied to two different metasurfaces to retrieve their effective
      homogeneous bi-anisotropic parameters. The effective layer of the same physical
      thickness is shown to produce the same response to plane wave excitation as the
      original metasurface.

PMID- 24104088
TI  - THz radiation from two electron-beams interaction within a bi-grating and a sub
      wavelength holes array composite sandwich structure.
AB  - Two electron-beams' interaction in a sandwich structure composed of a bi-grating
      and a sub-wavelength holes array is suggested to generate THz radiation in this
      paper. It shows that this system takes advantage of both bi-grating and sub
      wavelength holes array structures. The results demonstrate that surface waves on
      a bi-grating can couple with mimicking surface plasmons of a sub-wavelength holes
      array so that the wave-coupling is strong and the field intensity is high in this
      structure. Moreover, compared with the interaction in the bi-grating structure
      and sub-wavelength holes array structure, respectively, it shows that in this
      composite system the two electron-beams' interaction is more efficient and the
      modulation depth and radiation intensity have been enhanced significantly. The
      modulation depth and efficiency can reach 22% and 4%, respectively, and the
      starting current density is only 12 A/cm2. This radiation system may provide good
      opportunities for development of multi-electron beam-driven THz radiation
      sources.

PMID- 24104089
TI  - Waveguide coupled air-slot photonic crystal nanocavity for optomechanics.
AB  - We investigate a structure consisting of two parallel GaAs thin membranes with an
      air-slot type photonic crystal (PhC) nanocavity, which is designed to achieve
      highly efficient optomechanical coupling. The structure shows a large theoretical
      optomechanical coupling factor of ~990 GHz/nm. We designed, fabricated, and
      performed optical characterization of a system consisting of a grating coupler, a
      PhC waveguide, and a PhC nanocavity, which achieves highly efficient vertical
      emission using the band folding technique. The experimentally obtained overall
      efficiency is about 0.3% for a microscope objective lens with a moderate
      numerical aperture of 0.65. This waveguide coupled air-slot PhC nanocavity with
      efficient vertical light coupling can be useful for on-chip cavity optomechanical
      systems.

PMID- 24104090
TI  - Full field tabletop EUV coherent diffractive imaging in a transmission geometry.
AB  - We demonstrate the first general tabletop EUV coherent microscope that can image
      extended, non-isolated, non-periodic, objects. By implementing keyhole coherent
      diffractive imaging with curved mirrors and a tabletop high harmonic source, we
      achieve improved efficiency of the imaging system as well as more uniform
      illumination at the sample, when compared with what is possible using Fresnel
      zone plates. Moreover, we show that the unscattered light from a semi-transparent
      sample can be used as a holographic reference wave, allowing quantitative
      information about the thickness of the sample to be extracted from the retrieved
      image. Finally, we show that excellent tabletop image fidelity is achieved by
      comparing the retrieved images with scanning electron and atomic force microscopy
      images, and show superior capabilities in some cases.

PMID- 24104091
TI  - Transferring the attoclock technique to velocity map imaging.
AB  - Attosecond angular streaking measurements have revealed deep insights into the
      timing of tunnel ionization processes of atoms in intense laser fields. So far
      experiments of this type have been performed only with a cold-target recoil-ion
      momentum spectrometer (COLTRIMS). Here, we present a way to apply attosecond
      angular streaking experiments to a velocity map imaging spectrometer (VMIS) with
      few-cycle pulses at a repetition rate of 10 kHz and a high ionization yield per
      pulse. Three-dimensional photoelectron momentum distributions from strong-field
      ionization of helium with an elliptically polarized, sub-10-fs pulse were
      retrieved by tomographic reconstruction from the momentum space electron images
      and used for the analysis in the polarization plane. 

PMID- 24104092
TI  - Numerical characterization of an ultra-high NA coherent fiber bundle part I:
      modal analysis.
AB  - Advances in fiber optics and CCD technology in the last decades have allowed for
      a large reduction in outer diameter (from centimeters to submillimeter) of
      endoscopes. Attempts to reduce the outer diameter even further, however, have
      been hindered by the trade-off, inherent to conventional endoscopes, between
      outer diameter, resolution and field of view. Several groups have shown the
      feasibility of further miniaturization towards so called micro-endoscopes, albeit
      at the cost of a very reduced field of view. In previous work we presented the
      design of an ultra-high NA (0.928) Coherent FiberBundle (CFB) that, in
      combination with proximal wave front shaping, could be used to circumvent this
      trade-off thus paving the way for even smaller endoscopes. In this paper we
      analyze how the modal properties of such an ultra-high NA CFB determine the
      required input field to achieve any desired output field. We use the periodicity
      of the hexagonal lattice which characterizes a CFB, to define a unit cell of
      which we analyze the eigen-modes. During the modal analysis, we also take into
      account realistic variations in lattice constant, core size and core shape due to
      the limitations of the fabrication technology. Realistic values for these types
      of fabrication-induced irregularities were obtained via SEM images of a CFB
      fabricated according to the aforementioned design. The presence of these
      irregularities results, for a desired output, in the required input to be
      different from the required input for a defect-free CFB. We find that of the
      different types of fabrication-induced irregularities present in the CFB,
      variations in core ellipticity have the biggest impact on the required input for
      a given desired output. 

PMID- 24104093
TI  - Full-vectorial whispering-gallery-mode cavity analysis.
AB  - We present a full-vectorial three-dimensional whispering-gallery-mode microcavity
      analysis technique. With this technique, optical properties such as resonance
      wavelength, quality factor, and electromagnetic field distribution of a
      microcavity in the presence of individual nanoparticle adsorption can be
      simulated with high accuracy, even in the presence of field distortion from
      plasmon effects at a wavelength close to plasmon resonance. This formulation is
      applicable to a wide variety of whispering-gallery related problems, such as
      waveguide to cavity coupling and full wave propagation analysis of a general
      whispering-gallery-mode microcavity where axisymmetry along the azimuthal
      direction is not required. 

PMID- 24104094
TI  - All-optical photoacoustic imaging system using fiber ultrasound probe and hollow
      optical fiber bundle.
AB  - An all-optical 3D photoacoustic imaging probe that consists of an optical fiber
      probe for ultrasound detection and a bundle of hollow optical fibers for
      excitation of photoacoustic waves was developed. The fiber probe for ultrasound
      is based on a single-mode optical fiber with a thin polymer film attached to the
      output end surface that works as a Fabry Perot etalon. The input end of the
      hollow fiber bundle is aligned so that each fiber in the bundle is sequentially
      excited. A thin and flexible probe can be obtained because the probe system does
      not have a scanning mechanism at the distal end.

PMID- 24104095
TI  - A tunable notch filter using microelectromechanical microring with gap-variable
      busline coupler.
AB  - A microelectromechanical tunable notch filter using silicon-photonic freestanding
      waveguides is proposed, and the basic characteristics are experimentally
      investigated. The proposed filter is composed of a wavelength-tunable silicon
      microring resonator and a busline switch. The tunable microring consists of
      freestanding single-mode waveguides and air-gap directional waveguide couplers.
      The optical path length of the microring is varied physically by a displacement
      of electrostatic comb-drive actuator. The busline switch consists of a gap
      variable waveguide coupling mechanism, which enables coupling the tunable
      microring with the busline by another electrostatic comb-drive actuator. During
      the wavelength tuning of microring, the busline can be disconnected from the
      microring. Therefore, the proposed device operates as a hitless wavelength
      selective switch if they are connected in series. The waveguides are 320 nm in
      width and 340 nm in thickness. The resonant wavelength shift of the microring is
      9.96 nm at the voltage of 26 V with the actuator displacement of 1.0 MUm. The
      coupling to busline is adjusted from the switch-off state at the gap of 600 nm to
      the switch-on state corresponding to the critical coupling condition at the gap
      of 383 nm. The whole size of the wavelength-tunable filter with hitless mechanism
      is about 150 MUm by 80 MUm. Due to the capacitive operation of the comb-drive
      actuators, the power consumption is negligibly small.

PMID- 24104096
TI  - White emission of Yb2+:fluoride glasses efficiently excited with near-UV light.
AB  - Various Yb2+-containing fluoride glasses melting under a reductive atmosphere
      were prepared. The brightest white light emission was observed for an AlF3-based
      fluoride glass not containing Hf or Zr. The largest full width at half maximum of
      the white emission spectra was 202 nm. In addition, incorporation of chloride
      into the AlF3-based glass enabled efficient excitation with near-ultraviolet
      light corresponding to a GaN bandgap of 3.4 eV and the maximum internal quantum
      efficiency of Yb2+: AlF3-based fluoride glass was 42%.

PMID- 24104097
TI  - Optical properties of ordered carbon nanotube arrays grown in porous anodic
      alumina templates.
AB  - We have synthesized ordered carbon nanotube (CNT) arrays in porous anodic alumina
      (PAA) matrix, and have characterized their total optical reflectance and bi
      directional reflectance distribution function after each processing step of the
      microwave plasma chemical vapor deposition process (MPCVD). For a PAA sample
      without CNT growth, the reflectance shows an oscillating pattern with wavelength
      that agrees reasonably with a multilayer model. During the MPCVD process, heating
      the sample significantly reduces the reflectance by 30-40%, the plasma treatment
      reduces the reflectance by another 5-10%, and the CNT growth further reduces the
      reflectance by 2-3%. After an atomic layer deposition (ALD) process, the
      reflectance increases to the embedded CNT arrays. After etching and exposure of
      CNT tips, the reflectance almost returns to the original pattern with slightly
      higher reflectance. Bi-directional reflectance distribution function (BRDF)
      measurements show that the CNT-PAA surface is quite specular as indicated by a
      large lobe at the specular angle, while the secondary lobe can be attributed to
      surface roughness.

PMID- 24104098
TI  - Phase-sensitive amplification in a single bi-directional PPLN waveguide.
AB  - We investigate phase-sensitive amplification (PSA) and phase regeneration of a
      binary phase-shift keying (BPSK) signal using a single periodically poled lithium
      niobate (PPLN) waveguide. The PPLN is operated bi-directionally in order to
      simultaneously achieve phase correlated signals and phase-sensitive (PS)
      operation. We use injection-locking for carrier phase recovery and a lead
      zirconate titanate (PZT) fiber stretcher to correct path length deviations in the
      in-line phase regenerator. We observe a trade-off between high PS gain provided
      by high pumping power and stability of the device.

PMID- 24104099
TI  - High efficiency ring-lens supercritical angle fluorescence (SAF) detection for
      optimum bioassay performance.
AB  - We present a polymer biochip with embedded optics which allows the detection of
      supercritical angle fluorescence (SAF) without losses due to total internal
      reflection within the substrate. The chip design comprises structured spherical
      and aspherical optical elements on the bottom, while the top is chemically
      functionalized for direct binding of biomolecules. Furthermore, this design
      facilitates integration in lab-on-a-chip systems with appropriate microfluidics.
      In the confocal optical setup an ellipsoidal mirror is used for collection of SAF
      light above the critical angle of the water-polymer interface, which is detected
      by a photon-counting detector. The work presented here represents a proof of
      concept for performing sensitive and rapid point-of-care testing, using this low
      cost, robust and disposable optical biochip platform. The performance of the
      platform was validated using direct binding DNA and human IgG assays which
      yielded low limits of detection 10 pM for DNA and 10 pg/ml for human IgG.

PMID- 24104100
TI  - Broadband telecom transparency of semiconductor-coated metal nanowires: more
      transparent than glass.
AB  - Metallic nanowires (NW) coated with a high permittivity dielectric are proposed
      as means to strongly reduce the light scattering of the conducting NW, rendering
      them transparent at infrared wavelengths of interest in telecommunications. Based
      on a simple, universal law derived from electrostatics arguments, we find
      appropriate parameters to reduce the scattering efficiency of hybrid metal
      dielectric NW by up to three orders of magnitude as compared with the scattering
      efficiency of the homogeneous metallic NW. We show that metal@dielectric
      structures are much more robust against fabrication imperfections than analogous
      dielectric@metal ones. The bandwidth of the transparent region entirely covers
      the near IR telecommunications range. Although this effect is optimum at normal
      incidence and for a given polarization, rigorous theoretical and numerical
      calculations reveal that transparency is robust against changes in polarization
      and angle of incidence, and also holds for relatively dense periodic or random
      arrangements. A wealth of applications based on metal-NWs may benefit from such
      invisibility. 

PMID- 24104101
TI  - Enhancing light extraction efficiency of polymer light-emitting diodes with a 12
      fold photonic quasi crystal.
AB  - This work demonstrates the enhancement of light extraction of polymer light
      emitting diodes (PLEDs) by incorporating a 12-fold photonic quasi crystal (PQC)
      in the device structure. Multi-exposure two-beam interference technique combined
      with inductively coupled plasma etching was employed to pattern a 12-fold PQC
      structure on the ITO film on a glass substrate of the diode. The air-hole
      coverage (AHC) and etching depth dependences of the light emitting performance of
      the 12-fold PQC patterned PLEDs were investigated. For AHC within the range
      between 6.4% and 32.3%, a nearly constant enhancement of the luminance efficiency
      of the PQC PLEDs was observed. On the other hand, the light emitting performance
      of the PQC PLEDs is very sensitive to the etching depth. The photoluminescence
      intensity of the PQC PLEDs increases monotonically with the etching depth. In
      contrast, the electro luminance efficiency shows a non-monotonic dependence on
      etching depth with a maximum occurring at 55 nm etching depth. The maximum
      improvement of luminance efficiency of the 12-fold PQC PLEDs reaches nearly 95%
      compared with an un-patterned PLED at an injection current of 110 mA.

PMID- 24104102
TI  - Kilometer-range depth imaging at 1,550 nm wavelength using an InGaAs/InP single
      photon avalanche diode detector.
AB  - We have used an InGaAs/InP single-photon avalanche diode detector module in
      conjunction with a time-of-flight depth imager operating at a wavelength of 1550
      nm, to acquire centimeter resolution depth images of low signature objects at
      stand-off distances of up to one kilometer. The scenes of interest were scanned
      by the transceiver system using pulsed laser illumination with an average optical
      power of less than 600 uW and per-pixel acquisition times of between 0.5 ms and
      20 ms. The fiber-pigtailed InGaAs/InP detector was Peltier-cooled and operated at
      a temperature of 230 K. This detector was used in electrically gated mode with a
      single-photon detection efficiency of about 26% at a dark count rate of 16
      kilocounts per second. The system's overall instrumental temporal response was
      144 ps full width at half maximum. Measurements made in daylight on a number of
      target types at ranges of 325 m, 910 m, and 4.5 km are presented, along with an
      analysis of the depth resolution achieved.

PMID- 24104103
TI  - Optical phase modulation based on directly modulated reflection-mode OIL-VCSEL.
AB  - Optical phase modulation based on directly modulated reflection-mode optically
      injection-locked VCSEL is investigated based on standard OIL rate equations and
      reflection-mode OIL model. The phase information of both static and dynamic state
      is simulated. The difference of static state phase information between
      transmission- and reflection-mode OIL is numerically analyzed. With specific OIL
      parameters, the output power of directly modulated OIL-VCSEL remains constant and
      phase deviation of 0.934pi rad is obtained. Results show that a directly
      modulated OIL-VCSEL can function as a key component in QPSK or 8PSK transmitters.
      Preliminary 2.5 Gb/s PSK modulation characteristic is demonstrated
      experimentally.

PMID- 24104104
TI  - Q selection for an electro-optical earth imaging system: theoretical and
      experimental results.
AB  - This paper explores practical design considerations for selecting Q for an
      electro-optical earth imaging system, where Q is defined as (lambda FN) / pixel
      pitch. Analytical methods are used to show that, under imaging conditions with
      high SNR, increasing Q with fixed aperture cannot lead to degradation of image
      quality regardless of the angular smear rate of the system. The potential for
      degradation of image quality under low SNR is bounded by an increase of the
      detector noise scaling as Q. An imaging test bed is used to collect
      representative imagery for various Q configurations. The test bed includes real
      world errors such as image smear and haze. The value of Q is varied by changing
      the focal length of the imaging system. Imagery is presented over a broad range
      of parameters. 

PMID- 24104105
TI  - Nanoscale resolution for fluorescence microscopy via adiabatic passage.
AB  - We propose the use of the subwavelength localization via adiabatic passage
      technique for fluorescence microscopy with nanoscale resolution in the far field.
      This technique uses a Lambda-type medium coherently coupled to two laser pulses:
      the pump, with a node in its spatial profile, and the Stokes. The population of
      the Lambda system is adiabatically transferred from one ground state to the other
      except at the node position, yielding a narrow population peak. This coherent
      localization allows fluorescence imaging with nanometer lateral resolution. We
      derive an analytical expression to asses the resolution and perform a comparison
      with the coherent population trapping and the stimulated-emission-depletion
      techniques. 

PMID- 24104106
TI  - Automatic clocking optimization for compensating two-dimensional tolerances.
AB  - Clocking of lens elements is frequently used as an effective method of
      compensating for two-dimensional tolerances such as material inhomogeneity and
      surface figure errors. Typically, the lens designer has to determine the optimum
      angles of rotation by manually modeling lens element clocking in the commercial
      optical design software because the nature of errors resolved by lens clocking
      does not lead to good convergences for clocking optimization. In this paper, a
      method of automatic clocking optimization is developed. The method is implemented
      using a combination of particle swarm optimization algorithm and commercial
      optical design software. The optimum angles of rotation and predicted imaging
      performance are automatically calculated using this method. Methods of
      implementation and optimization examples are also given.

PMID- 24104107
TI  - Autocorrelation function of channel matrix in few-mode fibers with strong mode
      coupling.
AB  - Channel matrix plays a critical role in receiver design and ultimate channel
      performance. To fully describe the channel matrix of a few-mode fiber (FMF), we
      choose the generalized high-dimensional Gell-Mann matrices, an equivalent of the
      2-dimensional Pauli matrices used for a single-mode fiber (SMF), as the basis for
      the channel matrix decomposition. The frequency dependence of channel matrix can
      be studied in terms of the autocorrelation function (ACF), showing how fast
      channel changes in frequency domain. In this paper, we derive a canonical
      stochastic differential equation (SDE) for the FMF channel matrix in the regime
      of strong coupling. With the SDE, we develop an analytical form for the ACF of
      FMF channel matrix, from which the channel correlation bandwidth is obtained. 

PMID- 24104108
TI  - Pilot-symbols-aided cycle slip mitigation for DP-16QAM optical communication
      systems.
AB  - A pilot-symbols-aided phase unwrapping (PAPU), which utilizes the time-division
      multiplexed pilot symbols that are transmitted with data, is proposed to do cycle
      slip detection and correction with the carrier phase estimation (CPE). Numerical
      simulations for 10 Gbaud dual-polarization 16-ary quadrature amplitude modulation
      (DP-16QAM) systems show that the block averaging quadrature phase-shift keying
      (QPSK) partitioning with PAPU greatly eliminates the performance degradation
      caused by cycle slips, maintains a low CS probability with less influence of
      filter length, and achieves a bit-error-rate (BER) performance below soft
      decision forward error correction (FEC) limit 2 * 10-2 at 15 dB optical signal-to
      noise ratio with only 1.56% overhead and 6 MHz combined laser linewidth.

PMID- 24104109
TI  - Near-field thermal radiation between graphene-covered doped silicon plates.
AB  - The present work describes a theoretical investigation of the near-field thermal
      radiation between doped Si plates coated with a mono-layer of graphene. It is
      found that the radiative heat flux between doped Si plates can be either enhanced
      or suppressed by introducing graphene layer, depending on the Si doping
      concentration and chemical potential of graphene. Graphene can enhance the heat
      flux if it matches resonance frequencies of surface plasmon at vacuum-source and
      vacuum-receiver interfaces. In particular, significant enhancement is achieved
      when graphene is coated on both surfaces that originally does not support the
      surface plasmon resonance. The results obtained in this study provide an
      important guideline into enhancing the near-field thermal radiation between doped
      Si plates by introducing graphene. 

PMID- 24104110
TI  - Investigation of upconversion and near infrared emission properties in CeO2:
      Er3+, Yb3+ inverse opals.
AB  - The upconversion emission of rare earth ions can be modified in photonic
      crystals, however, the influence of upconversion emission modification of rare
      earths on near infrared emission has not been investigated yet in the photonic
      crystals. In the paper, CeO2: Er3+, Yb3+ inverse opals with the photonic band
      gaps at 545, 680 and 450 nm were prepared by polystyrene colloidal crystal
      templates. The upconversion and the near infrared emission properties of Er3+
      ions were systematically investigated in the CeO2: Er3+, Yb3+ inverse opals.
      Comparing with the reference sample, significant suppression of both the green
      and red upconversion luminescence of Er3+ ions were observed in the inverse
      opals. It is interesting that the infrared emission located at 1,560 nm was
      enhanced due to inhibition of upconversion emission in the inverse opals.
      Additionally, mechanism of upconversion emission of the inverse opal was
      discussed. The photon avalanche upconversion process is observed.

PMID- 24104111
TI  - Swept-frequency feedback interferometry using terahertz frequency QCLs: a method
      for imaging and materials analysis.
AB  - The terahertz (THz) frequency quantum cascade laser (QCL) is a compact source of
      high-power radiation with a narrow intrinsic linewidth. As such, THz QCLs are
      extremely promising sources for applications including high-resolution
      spectroscopy, heterodyne detection, and coherent imaging. We exploit the
      remarkable phase-stability of THz QCLs to create a coherent swept-frequency
      delayed self-homodyning method for both imaging and materials analysis, using
      laser feedback interferometry. Using our scheme we obtain amplitude-like and
      phase-like images with minimal signal processing. We determine the physical
      relationship between the operating parameters of the laser under feedback and the
      complex refractive index of the target and demonstrate that this coherent
      detection method enables extraction of complex refractive indices with high
      accuracy. This establishes an ultimately compact and easy-to-implement THz
      imaging and materials analysis system, in which the local oscillator, mixer, and
      detector are all combined into a single laser. 

PMID- 24104112
TI  - Oversampled triangulation of AWARE-10 monocentric ball lens using an auto
      stigmatic microscope.
AB  - In our development of multiscale, gigapixel camera architectures, there is a need
      for an accurate three-dimensional position alignment of large monocentric lenses
      relative to hemispherical dome structures. In this work we describe a method for
      estimating the position of the objective lens in our AWARE-10 four-gigapixel
      camera using the retro-reflected signal of a custom-designed auto-stigmatic
      microscope. We show that although the physical constraints of the system limit
      the numerical aperture of the microscope probe beam to around 0.016, which
      results in poor sensitivity in the axial direction, the lateral sensitivity is
      more than sufficient to verify that the position of the objective is within
      optical tolerances. 

PMID- 24104113
TI  - 3D beam reconstruction by fluorescence imaging.
AB  - We present a technique for mapping the complete 3D spatial intensity profile of a
      laser beam from its fluorescence in an atomic vapour. We propagate shaped light
      through a rubidium vapour cell and record the resonant scattering from the side.
      From a single measurement we obtain a camera limited resolution of 200 * 200
      transverse points and 659 longitudinal points. In constrast to invasive methods
      in which the camera is placed in the beam path, our method is capable of
      measuring patterns formed by counterpropagating laser beams. It has high
      resolution in all 3 dimensions, is fast and can be completely automated. The
      technique has applications in areas which require complex beam shapes, such as
      optical tweezers, atom trapping and pattern formation.

PMID- 24104114
TI  - Generation of arbitrary complex quasi-non-diffracting optical patterns.
AB  - Due to their unique ability to maintain an intensity distribution upon
      propagation, non-diffracting light fields are used extensively in various areas
      of science, including optical tweezers, nonlinear optics and quantum optics, in
      applications where complex transverse field distributions are required. However,
      the number and type of rigorously non-diffracting beams is severely limited
      because their symmetry is dictated by one of the coordinate system where the
      Helmholtz equation governing beam propagation is separable. Here, we demonstrate
      a powerful technique that allows the generation of a rich variety of quasi-non
      diffracting optical beams featuring nearly arbitrary intensity distributions in
      the transverse plane. These can be readily engineered via modifications of the
      angular spectrum of the beam in order to meet the requirements of particular
      applications. Such beams are not rigorously non-diffracting but they maintain
      their shape over large distances, which may be tuned by varying the width of the
      angular spectrum. We report the generation of unique spiral patterns and patterns
      involving arbitrary combinations of truncated harmonic, Bessel, Mathieu, or
      parabolic beams occupying different spatial domains. Optical trapping experiments
      illustrate the opto-mechanical properties of such beams. 

PMID- 24104115
TI  - Development of a low cost high precision three-layer 3D artificial compound eye.
AB  - Artificial compound eyes are typically designed on planar substrates due to the
      limits of current imaging devices and available manufacturing processes. In this
      study, a high precision, low cost, three-layer 3D artificial compound eye
      consisting of a 3D microlens array, a freeform lens array, and a field lens array
      was constructed to mimic an apposition compound eye on a curved substrate. The
      freeform microlens array was manufactured on a curved substrate to alter incident
      light beams and steer their respective images onto a flat image plane. The
      optical design was performed using ZEMAX. The optical simulation shows that the
      artificial compound eye can form multiple images with aberrations below 11 MUm;
      adequate for many imaging applications. Both the freeform lens array and the
      field lens array were manufactured using microinjection molding process to reduce
      cost. Aluminum mold inserts were diamond machined by the slow tool servo method.
      The performance of the compound eye was tested using a home-built optical setup.
      The images captured demonstrate that the proposed structures can successfully
      steer images from a curved surface onto a planar photoreceptor. Experimental
      results show that the compound eye in this research has a field of view of 87
      degrees . In addition, images formed by multiple channels were found to be evenly
      distributed on the flat photoreceptor. Additionally, overlapping views of the
      adjacent channels allow higher resolution images to be re-constructed from
      multiple 3D images taken simultaneously.

PMID- 24104116
TI  - The evanescent wavefield part of a cylindrical vector beam.
AB  - The evanescent wave of the cylindrical vector field is analyzed using the vector
      angular spectrum of the electromagnetic beam. Comparison between the
      contributions of the TE and TM terms of both the propagating and the evanescent
      waves associated with the cylindrical vector field in free space is demonstrated.
      The physical pictures of the evanescent wave and the propagating wave are well
      illustrated from the vectorial structure, which provides a new approach to
      manipulating laser beams by choosing the states of polarization in the cross
      section of the field. 

PMID- 24104117
TI  - Suppression of Rayleigh-scattering-induced noise in OEOs.
AB  - Optoelectronic oscillators (OEOs) are hybrid RF-photonic devices that promise to
      be environmentally robust high-frequency RF sources with very low phase noise.
      Previously, we showed that Rayleigh-scattering-induced noise in optical fibers
      coupled with amplitude-to-phase noise conversion in photodetectors and amplifiers
      leads to fiber-length-dependent noise in OEOs. In this work, we report on two
      methods for the suppression of this fiber-length-dependent noise: altering the
      amplitude-dependent phase delay of the OEO loops and suppressing the Rayleigh
      scattering-induced noise in optical fibers. We report a 20 dB reduction in the
      flicker phase noise of a 6 km OEO via these suppression techniques.

PMID- 24104118
TI  - Tri-wavelength laser generation based on neodymium doped disordered crystal
      waveguide.
AB  - We demonstrate a tri-wavelength laser generation from a Nd-doped calcium niobium
      gallium garnet disordered crystal waveguide. The laser threshold obtained was 83
      mW of launched pumping laser corresponding to a slope efficiency of 5.1%.
      According to the laser spectrum, the output light was found to be a tri
      wavelength laser, with wavelengths of 1058 nm, 1060 nm and 1064 nm, respectively.
      The stability of the output laser was investigated, which found that the output
      laser was a continuous laser.

PMID- 24104119
TI  - Photo-thermal modulation of surface plasmon polariton propagation at
      telecommunication wavelengths.
AB  - We report on photo-thermal modulation of thin film surface plasmon polaritons
      (SPP) excited at telecom wavelengths and traveling at a gold/air interface. By
      operating a modulated continuous-wave or a Q-switched nanosecond pump laser, we
      investigate the photo-thermally induced modulation of SPP propagation mediated by
      the temperature-dependent ohmic losses in the gold film. We use a fiber-to-fiber
      characterization set-up to measure accurately the modulation depth of the SPP
      signal under photo-thermal excitation. On the basis of these measurements, we
      extract the thermo-plasmonic coefficient of the SPP mode defined as the
      temperature derivative of the SPP damping constant. Next, we introduce a figure
      of merit which is relevant to characterize the impact of temperature onto the
      properties of bounded or weakly leaky SPP modes supported by a given metal at a
      given wavelength. By combining our measurements with tabulated values of the
      temperature-dependent imaginary part of gold dielectric function, we compute the
      thermo-optical coefficients (TOC) of gold at telecom wavelengths. Finally, we
      investigate a pulsed photo-thermal excitation of the SPP in the nanosecond
      regime. The experimental SPP depth of modulation obtained in this situation are
      found to be in fair agreement with the modulation depths computed by using our
      values of gold TOC.

PMID- 24104120
TI  - Fluorescence of bioaerosols: mathematical model including primary fluorescing and
      absorbing molecules in bacteria.
AB  - This paper describes a mathematical model of fluorescent biological particles
      composed of bacteria, viruses, or proteins. The fluorescent and/or light
      absorbing molecules included in the model are amino acids (tryptophan, etc.);
      nucleic acids (DNA, RNA, etc.); coenzymes (nicotinamide adenine dinucleotides,
      flavins, and vitamins B6 and K and variants of these); and dipicolinates. The
      concentrations, absorptivities, and fluorescence quantum yields are estimated
      from the literature, often with large uncertainties. The bioparticles in the
      model are spherical and homogeneous. Calculated fluorescence cross sections for
      particles excited at 266, 280, and 355 nm are compared with measured values from
      the literature for several bacteria, bacterial spores and albumins. The
      calculated 266- and 280-nm excited fluorescence is within a factor of 3.2 of the
      measurements for the vegetative cells and proteins, but overestimates the
      fluorescence of spores by a factor of 10 or more. This is the first reported
      modeling of the fluorescence of bioaerosols in which the primary fluorophores and
      absorbing molecules are included.

PMID- 24104121
TI  - Multicolour laser from a single bandgap-graded CdSSe alloy nanoribbon.
AB  - Multicolour lasing with wavelength varying from 578 nm to 640 nm is realized from
      a single bandgap-graded CdSSe alloy nanoribbon, by selecting the excited spot at
      room temperature. Though reabsorption is a serious problem to achieve lasing at
      short wavelength, multiple scatters on the nanoribbon form localized cavities,
      and thus lasing at different wavelengths is realized. By increasing the
      excitation area, multicolour lasing from the same nanoribbon is also observed
      simultaneously.

PMID- 24104122
TI  - InGaN/GaN microcolumn light-emitting diode arrays with sidewall metal contact.
AB  - In this study, we produce InGaN/GaN microcolumn LED (MC-LED) arrays having
      nonpolar metal sidewall contacts using a top-down method, where the metal
      contacts only with the sidewall of the columnar LEDs with an open top for
      transparency. The trapezoidal profile of the as-etched columns was altered to a
      rectangular profile through KOH treatment, exposing the nonpolar sidewalls. While
      the MC-LED with no treatment emitted no light because of the etch-damaged region,
      the MC-LEDs with KOH treatment exhibited much improved the electrical properties
      with the much higher shunt resistance due to the removal of the etch-damaged
      region. The optical output power was strongest for the MC-LED with a 5-min
      treatment indicating an almost complete removal of the damaged region.

PMID- 24104123
TI  - Distributed Bragg reflector structures based on PT-symmetric coupling with lowest
      possible lasing threshold.
AB  - A new approach towards the design of optimized distributed Bragg reflector (DBR)
      structures is proposed by taking advantage of recent developments related to the
      concept of parity-time (PT) in optics. This approach is based on using
      unidirectional gratings that provide coupling between co-propagating modes. Such
      couplers with PT symmetric gratings can provide co-directional mode coupling
      occurring only in one direction. This specific coupling property is achieved
      through a combined contribution of superimposed index and gain/loss modulations
      with same grating periodicity, but shifted with respect to one another by a
      quarter periods. Based on the transfer matrix approach, the transmission and
      reflection properties of the structure are modeled. One of the unique
      characteristics of the structure is very low lasing threshold. Such low threshold
      can be achieved by 100% reflectivity of the both Bragg grating mirrors, and by
      releasing the amplified signal in one single direction through a PT symmetric
      grating assisted co-directional coupler. Besides the lasing applications, the
      proposed structure can be implemented as an optical memory unit of replicating
      any input optical waveform. 

PMID- 24104124
TI  - Self-compensation of thermally induced depolarization in CaF2 and definite cubic
      single crystals.
AB  - Compensation of thermally induced depolarization in laser active elements at
      small birefringence without additional phase elements was proposed and observed
      experimentally. Requirements to the crystals were formulated. An order of
      magnitude reduction of depolarization degree was obtained experimentally. A
      further modification of the scheme was developed. 

PMID- 24104125
TI  - Simultaneous measurement of the microscopic dynamics and the mesoscopic
      displacement field in soft systems by speckle imaging.
AB  - The constituents of soft matter systems such as colloidal suspensions, emulsions,
      polymers, and biological tissues undergo microscopic random motion, due to
      thermal energy. They may also experience drift motion correlated over mesoscopic
      or macroscopic length scales, e.g. in response to an internal or applied stress
      or during flow. We present a new method for measuring simultaneously both the
      microscopic motion and the mesoscopic or macroscopic drift. The method is based
      on the analysis of spatio-temporal cross-correlation functions of speckle
      patterns taken in an imaging configuration. The method is tested on a translating
      Brownian suspension and a sheared colloidal glass. 

PMID- 24104126
TI  - Tunable quantum dot parametric source.
AB  - We report on the modeling of an electrically pumped nonlinear source for
      spontaneous parametric down-conversion in an AlGaAs single-sided Bragg waveguide.
      Laser emission from InAs quantum dots embedded in the waveguide core is designed
      to excite a Bragg pump mode at 950 nm. This mode is phase matched with two cross
      polarized total-internal-reflection fundamental signal and idler modes around
      1900 nm. Besides numerically evaluating the source efficiency, we discuss the
      crucial role played by the quantum dots in the practical implementation of the
      phase-matching condition along with the tuning capabilities of this promising
      active device.

PMID- 24104127
TI  - Electronic and thermal refractive index changes in ytterbium-doped fiber
      amplifiers.
AB  - We develop a theoretical framework to analyze the mechanism of refractive index
      changes (RIC) in double-clad Yb3+ doped optical fibers under resonant core or
      clad pumping, and with signal amplification. The model describes and compares
      thermal and electronic contributions to the phase shifts induced on the amplified
      signal at 1064 nm and the probe signal at 1550 nm, i.e. located inside and
      outside of the fiber amplification band, respectively. The ratio between the
      thermal and electronic phase shifts is evaluated as a function of the pump pulse
      duration, the gain saturation, the amplified beam power and for a variety of
      fiber parameters.

PMID- 24104128
TI  - Lens refractive index measurement based on fiber point-diffraction longitudinal
      interferometry.
AB  - A non-immersive lens refractive index measurement method based on fiber point
      diffraction longitudinal interferometry is presented. The lens imaging process is
      simplified to the single refraction of the back surface if the object point is
      located at the vertex of the front surface. The lens refractive index is derived
      through measuring its thickness, radius of curvature of the back surface, the
      distance between the object point and the image point. Experiments indicate its
      accuracy is better than 2.2 * 10-4. Since the front surface is excluded in the
      imaging process, even an aspherical lens could be accurately measured by this
      method.

PMID- 24104129
TI  - Optical characterization of two-dimensional array of 2,048 tilting micromirrors
      for astronomical spectroscopy.
AB  - A micromirror array composed of 2048 silicon micromirrors measuring 200 * 100
      MUm2 and tilting by 25 degrees  was developed as a reconfigurable slit mask for
      multi-object spectroscopy (MOS) in astronomy. The fill factor, contrast, and
      mirror deformation at both room and cryogenic temperatures were investigated.
      Contrast was measured using an optical setup that mimics a MOS instrument, and
      mirror deformation was characterized using a Twyman-Green interferometer. The
      results indicate that the array exhibited a fill factor of 82%, a contrast ratio
      of 1000:1, and surface mirror deformations of 8 nm and 27 nm for mirrors tilted
      at 298 K and 162 K, respectively.

PMID- 24104130
TI  - Two-photon absorption-induced photoacoustic imaging of Rhodamine B dyed
      polyethylene spheres using a femtosecond laser.
AB  - In the present paper we demonstrate the possibility to image dyed solids, i.e.
      Rhodamine B dyed polyethylene spheres, by means of two-photon absorption-induced
      photoacoustic scanning microscopy. A two-photon luminescence image is recorded
      simultaneously with the photoacoustic image and we show that location and size of
      the photoacoustic and luminescence image match. In the experiments photoacoustic
      signals and luminescence signals are generated by pulses from a femtosecond
      laser. Photoacoustic signals are acquired with a hydrophone; luminescence signals
      with a spectrometer or an avalanche photo diode. In addition we derive the
      expected dependencies between excitation intensity and photoacoustic signal for
      single-photon absorption, two-photon absorption and for the combination of both.
      In order to verify our setup and evaluation method the theoretical predictions
      are compared with experimental results for liquid and solid specimens, i.e. a
      carbon fiber, Rhodamine B solution, silicon, and Rhodamine B dyed microspheres.
      The results suggest that the photoacoustic signals from the Rhodamine B dyed
      microspheres do indeed stem from two-photon absorption. 

PMID- 24104131
TI  - Simultaneous generation of sub-20 fs deep and vacuum ultraviolet pulses in a
      single filamentation cell and application to time-resolved photoelectron imaging.
AB  - Sub-20 fs pulses of the third, fourth, and fifth harmonics of a Ti:sapphire laser
      are simultaneously generated using cascaded four-wave mixing in filamentation
      propagation of the fundamental frequency and the second harmonic pulses in Ne
      gas. Reflective optics under vacuum are employed after the four-wave mixing to
      minimize material dispersion of the optical pulses. The cross-correlation between
      198 and 159 nm pulses of 18 fs is achieved without dispersion compensation. This
      new light source is applied to time-resolved photoelectron imaging of carbon
      disulfide (CS2).

PMID- 24104132
TI  - Metal-optic cavity for a high efficiency sub-fF germanium photodiode on a silicon
      waveguide.
AB  - We propose two designs of nanoscale sub-fF germanium photodiodes which are
      efficiently integrated with silicon waveguides. The metal-optic cavities are
      simulated with the finite difference time domain method and optimized using
      critical coupling concepts. One design is for a metal semiconductor metal
      photodiode with <200 aF capacitance, 39% external quantum efficiency, and 0.588
      (lambda/n)3 cavity volume at 1.5 um wavelength. The second design is for a
      vertical p-i-n photodiode with <100 aF capacitance, 51% external quantum
      efficiency, and 0.804 (lambda/n)3 cavity volume. Both designs make use of CMOS
      compatible materials germanium and aluminum metal for potential future monolithic
      integration with silicon photonics.

PMID- 24104133
TI  - Drop-port study of microresonator frequency combs: power transfer, spectra and
      time-domain characterization.
AB  - We use a drop-port geometry to characterize frequency combs generated from
      silicon nitride on-chip microresonators in the normal group velocity regime. In
      sharp contrast with the traditional transmission geometry, we observe smooth
      output spectra with comparable powers in the pump and adjacent comb lines. The
      power transfer into the comb may be explained to a large extent by the coupling
      parameters characterizing the linear operation of the resonances studied.
      Furthermore, comparison of thru- and drop-port spectra shows that much of the ASE
      noise is filtered out by transmission to the drop-port. Autocorrelation
      measurements are performed on the drop-port output, without the need to filter
      out or suppress the strong pump line as is necessary in thru-port experiments.
      Passively mode-locked pulses with low background are observed in a normal
      dispersion microcavity.

PMID- 24104134
TI  - Synthetic Fourier transform light scattering.
AB  - We present synthetic Fourier transform light scattering, a method for measuring
      extended angle-resolved light scattering (ARLS) from individual microscopic
      samples. By measuring the light fields scattered from the sample plane and
      numerically synthesizing them in Fourier space, the angle range of the ARLS
      patterns is extended up to twice the numerical aperture of the imaging system
      with unprecedented sensitivity and precision. Extended ARLS patterns of
      individual microscopic polystyrene beads, healthy human red blood cells (RBCs),
      and Plasmodium falciparum-parasitized RBCs are presented.

PMID- 24104135
TI  - Phase measurement of fast light pulse in electromagnetically induced absorption.
AB  - We report the phase measurement of a fast light pulse in electromagnetically
      induced absorption (EIA) of the 5S1/2 (F = 2)-5P3/2 (F' = 3) transition of 87Rb
      atoms. Using a beat-note interferometer method, a stable measurement without
      phase dithering of the phase of the probe pulse before and after it has passed
      through the EIA medium was achieved. Comparing the phases of the light pulse in
      air and that of the fast light pulse though the EIA medium, the phase of the fast
      light pulse at EIA resonance was not shifted and maintained to be the same as
      that of the free-space light pulse. The classical fidelity of the fast light
      pulse according to the advancement of the group velocity by adjusting the atomic
      density was estimated to be more than 97%.

PMID- 24104137
TI  - Investigations on single and multiple pulse laser-induced damages in HfO2/SiO2
      multilayer dielectric films at 1,064 nm.
AB  - Nanosecond single and multiple pulse laser damage studies on HfO2/SiO2 high
      reflective coatings were performed at 1064 nm. The evolution of LIDT and 100%
      damage probability threshold under multiple irradiations revealed that fatigue
      effects were affected by both laser fluence and shot numbers. And the damage
      probability curves exhibiting different behaviors confirmed experimentally that
      this fatigue effect of the dielectric coatings was due to material modification
      rather than statistical effects. By using a model assuming Gaussian distribution
      of defect threshold, the fitting results of LID probability curves indicated the
      turning point appeared in the damage probability curves under large shot number
      irradiations was just the representation of the existence of newly created
      defects. The thresholds of these newly created defects were exponential decrease
      with irradiated shot numbers. Besides, a new kind of damage morphologies under
      multiple shot irradiations were characterized to further expose the fatigue
      effect caused by cumulative laser-induced material modifications.

PMID- 24104136
TI  - Low loss 40 Gbit/s silicon modulator based on interleaved junctions and
      fabricated on 300 mm SOI wafers.
AB  - We demonstrate high-speed silicon modulators based on carrier depletion in
      interleaved pn junctions fabricated on 300 mm-SOI wafers using CMOS foundry
      facilities. 950 um-long Mach Zehnder (MZ) and ring resonator (RR) modulator with
      a 100 um radius, were designed, fabricated and characterized. 40 Gbit/s data
      transmission has been demonstrated for both devices. The MZ modulator exhibited a
      high extinction ratio of 7.9 dB with only 4 dB on-chip losses at the operating
      point.

PMID- 24104138
TI  - Real-time calibration of laser absorption spectrometer using spectral correlation
      performed with an in-line gas cell.
AB  - A real-time drift correction and calibration method using spectral correlation
      based on a revolving in-line gas cell for laser-based spectroscopic trace-gas
      measurements has been developed and evaluated experimentally. This technique is
      relatively simple to implement in laser spectroscopy systems and assures long
      term stability of trace-gas measurements by minimizing the effects of external
      sources of drift in real-time. Spectroscopic sensitivity sufficient for
      environmental monitoring and effective drift suppression has been achieved for
      long-term measurements of CO2 with a quantum cascade laser based spectrometer.

PMID- 24104139
TI  - Dynamic bending compensation while focusing through a multimode fiber.
AB  - Multimode fiber endoscopes have recently been shown to provide sub-micrometer
      resolution, however, imaging through a multimode fiber is highly sensitive to
      bending. Here we describe the implementation of a coherent beacon source placed
      at the distal tip of the multimode fiber, which can be used to compensate for the
      effects of bending. In the first part of this paper, we show that a diffraction
      limited focused spot can be generated at the distal tip of the multimode fiber
      using the beacon. In the second part, we demonstrate focusing even when the fiber
      is bent by dynamically compensating for it. The speckle pattern at the proximal
      fiber end, generated by the beacon source placed at its distal end, is highly
      dependent on the fiber conformation. We experimentally show that by intensity
      correlation, it is possible to identify the fiber conformation and maintain a
      focus spot while the fiber is bent over a certain range. Once the fiber
      configuration is determined, previously calibrated phase patterns could be stored
      for each fiber conformation and used to scan the distal spot and perform imaging.

PMID- 24104140
TI  - Research on a novel composite structure Er3+-doped DBR fiber laser with a pi
      phase shifted FBG.
AB  - A simple composite cavity structure Er3+-doped fiber laser was proposed and
      demonstrated experimentally. The resonant cavity consists of a pair of uniform
      fiber Bragg gratings (FBGs) and a pi-phase shifted FBG. By introducing the pi
      phase shifted FBG into the cavity as the selective wavelength component, it can
      increase the effective length of the laser cavity and suppress the multi
      longitudinal modes simultaneously. The narrow linewidth of 900 Hz and low RIN of 
      95 dB/Hz were obtained. And the lasing wavelength was rather stable with the pump
      power changing. The SMRS was more than 67 dB. The results show that the proposed
      fiber laser has a good performance and considerable potential application for
      fiber sensor and optical communication.

PMID- 24104141
TI  - Spectral response of an upconversion detector and spectrometer.
AB  - We investigate the spectral response of an upconversion detector theoretically
      and experimentally, and discuss implications for its use as an infrared
      spectrometer. Upconversion detection is based on high-conversion-efficiency, sum
      frequency generation (SFG). The spectral selectivity of an upconversion
      spectrometer is determined by the SFG spectral response function. This function
      changes with varying pump power. Working at maximum internal conversion
      efficiency is desirable for high sensitivity of the system, but the spectral
      response function is different at this pump power compared to the response
      function at low power. We calculate the theoretical spectral response of the
      upconversion detector as a function of pump power and obtain excellent agreement
      with upconversion spectra measured in a periodically poled LiNbO3 waveguide.

PMID- 24104142
TI  - Pulsed dipole radiation in a transformation-optics wedge waveguide designed by
      azimuthal space compression.
AB  - A transformation-optics wedge waveguide designed for the simultaneous collection
      and directional collimation of pulsed dipole radiation is described and tested
      with numerical simulation. Azimuthal compression of free space toward a narrow
      fan-shaped waveguide sector allows dipole pulse radiation in free space to be
      transformed into a directional non-dispersive pulse propagating within that
      sector. The collection and collimation ability of the proposed structure is
      compared with classical approaches using metallic wedge mirrors and parabolic
      mirrors, which inherently allow multiple internal reflections and thus generate
      significant pulse distortion and low light-collection efficiency. It is shown
      that the optical pulse generated by the dipole and propagated through the
      proposed transformation-optics waveguide maintains its original shape within the
      structure, and demonstrates enhanced optical power. 

PMID- 24104143
TI  - A one-dimensional tunable magnetic metamaterial.
AB  - We present experimental data on a one-dimensional super-conducting metamaterial
      that is tunable over a broad frequency band. The basic building block of this
      magnetic thin-film medium is a single-junction (rf-) superconducting quantum
      interference device (SQUID). Due to the nonlinear inductance of such an element,
      its resonance frequency is tunable in situ by applying a dc magnetic field. We
      demonstrate that this results in tunable effective parameters of our metamaterial
      consisting of 54 rf-SQUIDs. In order to obtain the effective magnetic
      permeability MUr,eff from the measured data, we employ a technique that uses only
      the complex transmission coefficient S21.

PMID- 24104144
TI  - Linearized silicon modulator based on a ring assisted Mach Zehnder inteferometer.
AB  - We demonstrate a Linearized Ring Assisted Mach-Zehnder Interferometer (L-RAMZI)
      modulator in a miniature silicon device. We measure a record high degree of
      linearization for a silicon device, with a Spurious Free Dynamic Range (SFDR) of
      106dB/Hz2/3 at 1GHz, and 99dB/Hz2/3 at 10GHz.

PMID- 24104145
TI  - Simultaneous generation of monoenergetic tunable protons and carbon ions from
      laser-driven nanofoils.
AB  - Simultaneous generation of monoenergetic tunable protons and carbon ions from
      intense laser multi-component nanofoil interaction is demonstrated by using
      particle-in-cell simulations. It is shown that, the protons with the largest
      charge-to-mass ratio are instantly separated from other ion species and are
      efficiently accelerated in the "phase stable" way. The carbon ions always ride on
      the heavier oxygen ion front with an electron-filling gap between the protons and
      carbon ions. At the cost of widely spread oxygen ions, monoenergetic collimated
      protons and carbon ions are obtained simultaneously. By modulating the heavier
      ion densities in the foil, it is capable to control the final beam quality, which
      is well interpreted by a simple analytical model. 

PMID- 24104146
TI  - Enhancing the radiation efficiency of dye doped whispering gallery mode
      microresonators.
AB  - We present a novel form of a Whispering Gallery Mode (WGM) sensor that exploits
      dye doped polystyrene microspheres, as active resonators, positioned onto the tip
      of a Microstructured Optical Fiber (MOF) as a means of overcoming the limited Q
      factors for small resonators. We show that it is possible to substantially
      enhance the fluorescence emission of selected WGMs of the microspheres, resulting
      in an increase of the signal-to-noise ratio of the modes and of the effective Q
      factor. This is done by positioning the resonator into one of the holes of a
      suspended core MOF and matching the resonator diameter with the hole diameter
      where it sits, effectively breaking the symmetry of the environment surrounding
      the sphere. Furthermore we demonstrate that using this experimental
      configuration, the lasing efficiency of the dye-doped microspheres is also
      significantly enhanced, which also contributes to an enhancement in the observed
      Q-factor. 

PMID- 24104147
TI  - Accelerated solution of the frequency-domain Maxwell's equations by engineering
      the eigenvalue distribution of the operator.
AB  - We introduce a simple method to accelerate the convergence of iterative solvers
      of the frequency-domain Maxwell's equations for deep-subwavelength structures.
      Using the continuity equation, the method eliminates the high multiplicity of
      near-zero eigenvalues of the operator while leaving the operator nearly positive
      definite. The impact of the modified eigenvalue distribution on the accelerated
      convergence is explained by visualizing residual vectors and residual
      polynomials.

PMID- 24104148
TI  - Processing and phase analysis of fringe patterns with contrast reversals.
AB  - A method for demodulating fringe patterns containing contrast reversals is
      proposed. It consists of two steps. First, the absolute value of the fringe
      intensity distribution with its background removed is calculated. Then, two
      dimensional continuous wavelet transform with enhanced ridge extraction algorithm
      is applied to extract the fringe phase map. Proposed approach allows to dispose
      of phase jumps along the contrast reversal bands. The method requires only one
      image and has no special demands concerning the fringe pattern design. Method
      validity and robustness is confirmed using experimentally acquired time-averaged
      interferograms of vibrating silicon micromembranes.

PMID- 24104149
TI  - Spectral shifts and spectral switches produced by the scattering system of two
      anisotropic particles in different distance.
AB  - We investigate the scattering of polychromatic plane light wave incident upon a
      system formed with two anisotropic particles in different distance. The
      analytical expression for the spectrum of the scattered field is derived.
      Numerical examples show the phenomena of spectral shifts and spectral switches of
      the scattered field. The influences of the scattering direction and the
      difference of the particles on the spectral switch are illustrated. 

PMID- 24104150
TI  - Optimization of output power in a fiber optical parametric oscillator.
AB  - Fiber optical parametric oscillators (FOPOs) are coherent sources that can
      provide ultra-broadband tunability and high output power levels and are been
      considered for applications such as medical imaging and sensing. While most
      recent literature has focused on advancing the performance of these devices
      experimentally, theoretical studies are still scarce. In contrast, ordinary laser
      theory is very mature, has been thoroughly studied and is now well understood
      from the point of view of fundamental physics. In this work, we present a
      theoretical study of OPOs and in particular we theoretically discuss the process
      of gain saturation in optical parametric amplifiers. In order to emphasize the
      significant difference between the two coherent sources, we compare the optimized
      coupling ratios for maximum output powers of the ordinary laser and the optical
      parametric oscillator and demonstrate that in contrast to ordinary lasers,
      highest output powers in optical parametric oscillators are achieved with output
      coupling ratios close to 1. We confirm experimentally our theoretical studies by
      building a narrowband fiber optical parametric oscillator at 1450nm with multi
      watt output power. We show that the device is robust to intracavity losses and
      achieve peak power as high as 2.4W. 

PMID- 24104151
TI  - Experimental study on subaperture testing with iterative triangulation algorithm.
AB  - Applying the iterative triangulation stitching algorithm, we provide an
      experimental demonstration by testing a Phi120 mm flat mirror, a Phi1450 mm off
      axis parabolic mirror and a convex hyperboloid mirror. By comparing the stitching
      results with the self-examine subaperture, it shows that the reconstruction
      results are in consistent with that of the subaperture testing. As all the
      experiments are conducted with a 5-dof adjustment platform with big adjustment
      errors, it proves that using the above mentioned algorithm, the subaperture
      stitching can be easily performed without a precise positioning system. In
      addition, with the algorithm, we accomplish the coordinate unification between
      the testing and processing that makes it possible to guide the processing by the
      stitching result.

PMID- 24104153
TI  - High quantum-efficiency photon-number-resolving detector for photonic on-chip
      information processing.
AB  - The integrated optical circuit is a promising architecture for the realization of
      complex quantum optical states and information networks. One element that is
      required for many of these applications is a high-efficiency photon detector
      capable of photon-number discrimination. We present an integrated photonic system
      in the telecom band at 1550 nm based on UV-written silica-on-silicon waveguides
      and modified transition-edge sensors capable of number resolution and over 40 %
      efficiency. Exploiting the mode transmission failure of these devices, we
      multiplex three detectors in series to demonstrate a combined 79 % +/- 2 %
      detection efficiency with a single pass, and 88 % +/- 3 % at the operating
      wavelength of an on-chip terminal reflection grating. Furthermore, our optical
      measurements clearly demonstrate no significant unexplained loss in this system
      due to scattering or reflections. This waveguide and detector design therefore
      allows the placement of number-resolving single-photon detectors of predictable
      efficiency at arbitrary locations within a photonic circuit - a capability that
      offers great potential for many quantum optical applications.

PMID- 24104152
TI  - Cuticle structure of the scarab beetle Cetonia aurata analyzed by regression
      analysis of Mueller-matrix ellipsometric data.
AB  - Since one hundred years it is known that some scarab beetles reflect elliptically
      and near-circular polarized light as demonstrated by Michelson for the beetle
      Chrysina resplendens. The handedness of the polarization is in a majority of
      cases left-handed but also right-handed polarization has been found. In addition,
      brilliant colors with metallic shine are observed. The polarization and color
      effects are generated in the beetle exoskeleton, the so-called cuticle. The
      objective of this work is to demonstrate that structural parameters and materials
      optical functions of these photonic structures can be extracted by advanced
      modeling of spectral multi-angle Mueller-matrix data recorded from beetle
      cuticles. A dual-rotating compensator ellipsometer is used to record normalized
      Mueller-matrix data in the spectral range 400 - 800 nm at angles of incidence in
      the range 25-75 degrees . Analysis of data measured on the scarab beetle Cetonia
      aurata are presented in detail. The model used in the analysis mimics a chiral
      nanostructure and is based on a twisted layered structure. Given the complexity
      of the nanostructure, an excellent fit between experimental and model data is
      achieved. The obtained model parameters are the spectral variation of the
      refractive indices of the cuticle layers and structural parameters of the chiral
      structure.

PMID- 24104154
TI  - Carrier-envelope phase stable few-cycle pulses at 400 kHz for electron-ion
      coincidence experiments.
AB  - Coincident electron-ion detection after photoionization in a "reaction
      microscope" is a very powerful tool to study atomic and molecular dynamics.
      However, the implementation of this tool in the field of attosecond science has
      so far been rather limited, due to the lack of high repetition rate laser sources
      capable of delivering few-cycle pulses with sufficient energy per pulse. In this
      article, the development of a Non-collinear Optical Parametric Amplifier (NOPA)
      capable of delivering Carrier-Envelope Phase (CEP) stable pulses with sub-6 fs
      duration and pulse energies in the few-uJ range is presented. The potential of
      combining the high repetition rate source and a reaction microscope operating at
      this high frequency is demonstrated in a proof-of-principle experiment on strong
      field ionization of Ar atoms.

PMID- 24104155
TI  - Absorption engineering of NbN nanowires deposited on silicon nitride nanophotonic
      circuits.
AB  - We investigate the absorption properties of U-shaped niobium nitride (NbN)
      nanowires atop nanophotonic circuits. Nanowires as narrow as 20nm are realized in
      direct contact with Si3N4 waveguides and their absorption properties are
      extracted through balanced measurements. We perform a full characterization of
      the absorption coefficient in dependence of length, width and separation of the
      fabricated nanowires, as well as for waveguides with different cross-section and
      etch depth. Our results show excellent agreement with finite-element analysis
      simulations for all considered parameters. The experimental data thus allows for
      optimizing absorption properties of emerging single-photon detectors co
      integrated with telecom wavelength optical circuits. 

PMID- 24104156
TI  - A continuous wave 10 W cryogenic fiber amplifier at 1015 nm and frequency
      quadrupling to 254 nm.
AB  - A stable, continuous wave, single frequency fiber amplifier system at 1015 nm
      with 10 W output power is presented. It is based on a large mode double clad
      fiber cooled to liquid nitrogen temperature. The amplified light is frequency
      quadrupled to 254 nm and used for spectroscopy of the 61S -> 63P transition in
      mercury.

PMID- 24104157
TI  - Orthogonally polarized dual-wavelength single-longitudinal-mode Tm,Ho:LLF laser.
AB  - We first report a diode-pumped continuous wave orthogonally polarized dual
      wavelength single-longitudinal-mode laser with a single c-cut Tm,Ho:LuLiF4 laser
      crystal. The simultaneous dual-wavelength single-longitudinal-mode laser near 2
      MUm is realized by using two uncoated intracavity Fabry-Perot etalons. The output
      wavelengths are 2064 nm in pi-polarization and 2066 nm in sigma-polarization
      respectively, which are orthogonal to each other. At the absorbed pump power of 1
      W, the maximum single-longitudinal-mode output powers at 2064 and 2066 nm are 76
      and 32 mW respectively. The orthogonally polarized dual-wavelength single
      longitudinal-mode laser is possible to be applied to the 2 MUm differential
      absorption lidar and the generation of THz radiation.

PMID- 24104158
TI  - Long-range coupling of silicon photonic waveguides using lateral leakage and
      adiabatic passage.
AB  - We present a new approach to long range coupling based on a combination of
      adiabatic passage and lateral leakage in thin shallow ridge waveguides on a
      silicon photonic platform. The approach enables transport of light between two
      isolated waveguides through a mode of the silicon slab that acts as an optical
      bus. Due to the nature of the adiabatic protocol, the bus mode has minimal
      population and the transport is highly robust. We prove the concept and examine
      the robustness of this approach using rigorous modelling. We further demonstrate
      the utility of the approach by coupling power between two waveguides whilst
      bypassing an intermediate waveguide. This concept could form the basis of a new
      interconnect technology for silicon integrated photonic chips. 

PMID- 24104159
TI  - Highly-efficient fully resonant vertical couplers for InP active-passive
      monolithic integration using vertically phase matched waveguides.
AB  - A new active-passive monolithic integration approach for photonic components
      based on vertical evanescent coupling is presented. Two vertically stacked
      waveguides are used in order to provide full resonant power transfer between them
      and avoiding the need of tapered structures. Light confinement in each waveguide
      is achieved combining strong lateral asymmetric structures and bent waveguides,
      both defined during lithography. Low propagation losses for the active waveguide
      and coupling efficiencies to the passive section as high as 97% have been
      obtained. 

PMID- 24104161
TI  - Picosecond and nanosecond pulse delivery through a hollow-core Negative Curvature
      Fiber for micro-machining applications.
AB  - We present high average power picosecond and nanosecond pulse delivery at 1030 nm
      and 1064 nm wavelengths respectively through a novel hollow-core Negative
      Curvature Fiber (NCF) for high-precision micro-machining applications. Picosecond
      pulses with an average power above 36 W and energies of 92 uJ, corresponding to a
      peak power density of 1.5 TWcm-2 have been transmitted through the fiber without
      introducing any damage to the input and output fiber end-faces. High-energy
      nanosecond pulses (>1 mJ), which are ideal for micro-machining have been
      successfully delivered through the NCF with a coupling efficiency of 92%.
      Picosecond and nanosecond pulse delivery have been demonstrated in fiber-based
      laser micro-machining of fused silica, aluminum and titanium.

PMID- 24104160
TI  - Two-colour generation in a chirped seeded free-electron laser: a close look.
AB  - We present the experimental demonstration of a method for generating two
      spectrally and temporally separated pulses by an externally seeded, single-pass
      free-electron laser operating in the extreme-ultraviolet spectral range. Our
      results, collected on the FERMI@Elettra facility and confirmed by numerical
      simulations, demonstrate the possibility of controlling both the spectral and
      temporal features of the generated pulses. A free-electron laser operated in this
      mode becomes a suitable light source for jitter-free, two-colour pump-probe
      experiments. 

PMID- 24104162
TI  - Determination of the effective refractive index of nanoparticulate ITO layers.
AB  - Nanoparticles of transparent conducting oxides, such as indium tin oxide, can be
      used in printing techniques to generate functional layers for various
      optoelectronic devices. Since these deposition methods do not create fully
      consolidated films, the optical properties of such layers are expected to be
      notably different from those of the bulk material and should be characterized on
      their own. In this work we present a way to measure the effective refractive
      index of a particulate ITO layer by refraction of light. The obtained data points
      are used to identify an accurate layer model for spectroscopic ellipsometry. In
      this way the complex refractive index of the particle layer is determined in a
      wide spectral range from ultra violet to near infrared. 

PMID- 24104163
TI  - Effect of bending on surface plasmon resonance spectrum in microstructured
      optical fibers.
AB  - We analyzed the effect of fiber bending on spectral position and strength of the
      surface plasmon resonance arising due to the interaction of the fundamental mode
      guided in the core of the microstructured fiber with a metal layer. Fully
      vectorial simulations were performed using the finite element method with
      perfectly matched layers boundary conditions. To conduct the simulations, we
      adopted the concept of an equivalent bent fiber developed recently on the ground
      of transformation optics formalism. In this approach, the bent fiber with a metal
      layer is replaced by an equivalent fiber with appropriate spatial distributions
      of electric permittivity and magnetic permeability tensors. The obtained results
      explain the mechanisms responsible for the change in the SPR spectrum induced by
      bending and by the geometry of the microstructured fiber. By modifying the holes
      layout in the microstructured cladding, we designed the fiber, in which the depth
      of the surface plasmon resonance is in a high degree tunable by bending. 

PMID- 24104164
TI  - Polarization-time coding for PDL mitigation in long-haul PolMux OFDM systems.
AB  - In this paper, we present a numerical, theoretical and experimental study on the
      mitigation of Polarization Dependent Loss (PDL) with Polarization-Time (PT) codes
      in long-haul coherent optical fiber transmissions using Orthogonal Frequency
      Division Multiplexing (OFDM). First, we review the scheme of a polarization
      multiplexed (PolMux) optical transmission and the 2 * 2 MIMO model of the optical
      channel with PDL. Second, we introduce the Space-Time (ST) codes originally
      designed for wireless Rayleigh fading channels, and evaluate their performance,
      as PT codes, in mitigating PDL through numerical simulations. The obtained
      behaviors and coding gains are different from those observed on the wireless
      channel. In particular, the Silver code performs better than the Golden code and
      the coding gains offered by PT codes and forward-error-correction (FEC) codes
      aggregate. We investigate the numerical results through a theoretical analysis
      based on the computation of an upper bound of the error probability of the
      optical channel with PDL. The derived upper bound yields a design criterion for
      optimal PDL-mitigating codes. Furthermore, a transmission experiment of PDL
      mitigation in a 1,000 km optical fiber link with inline PDL validates the
      numerical and theoretical findings. The results are shown in terms of Q-factor
      distributions. The mean Q-factor is improved with PT coding and the variance is
      also narrowed.

PMID- 24104165
TI  - Self-seeded lasing in ionized air pumped by 800 nm femtosecond laser pulses.
AB  - We report on the lasing in air and pure nitrogen gas pumped by a single 800 nm
      femtosecond laser pulse. Depending on gas pressure, incident laser power and beam
      convergence, different lasing lines are observed in the forward direction with
      rapid change of their relative intensities. The lines are attributed to
      transitions between vibrational and rotational levels of the first negative band
      of the singly charged nitrogen molecule-ion. We show that self-seeding plays an
      important role in the observed intensity changes. 

PMID- 24104166
TI  - A time- and wavelength-division multiplexing sensor network with ultra-weak fiber
      Bragg gratings.
AB  - A time- and wavelength-division multiplexing sensor network based on ultra-weak
      fiber Bragg gratings (FBGs) was proposed. The low insertion loss and the high
      multiplexing capability of the proposed sensor network were investigated through
      both theoretical analysis and experimental study. The demodulation system, which
      consists of two semiconductor optical amplifiers and one high-speed charge
      coupled device module, was constructed to interrogate 2000 serial ultra-weak FBGs
      with peak reflectivity ranging from -47 dB to -51 dB and a spatial resolution of
      2 m along an optical fiber. The distinct advantages of the proposed sensor
      network make it an excellent candidate for the large-scale sensing network.

PMID- 24104167
TI  - A single-channel 1.92 Tbit/s, 64 QAM coherent optical pulse transmission over 150
      km using frequency-domain equalization.
AB  - We demonstrate a single-channel 1.92 Tbit/s, 64 QAM coherent optical pulse
      optical time-division multiplexing (OTDM) transmission by utilizing frequency
      domain equalization (FDE). FDE makes it possible to compensate precisely for the
      waveform distortions caused by hardware imperfections thus greatly improving the
      error vector magnitude (EVM) of the demodulated 64 QAM signal compared with that
      obtained with a conventional FIR filter. As a result, a coherent 64 QAM OTDM
      transmission over 150 km with a bit error rate of below the forward error
      correction limit of 2 x 10-3 (requiring 7% overhead) was achieved for the first
      time.

PMID- 24104168
TI  - Towards more accurate microcavity sensors: maximum likelihood estimation applied
      to a combination of quality factor and wavelength shifts.
AB  - Optical microcavities are widely used for biological and chemical sensing
      applications. In these devices, a sensing event is estimated by measuring the
      shift in the resonant wavelength, or in the quality factor of the microcavity.
      However, all published works to date only use one of these measures to estimate
      the sensing event. Here, we show that the estimation accuracy of a sensing event
      can be improved by employing a combination of both the quality factor and the
      resonant wavelength measurements in a microcavity sensor. We further demonstrate
      an experimental application of this model by introducing a refractive index
      change for a microtoroidal cavity sensor immersed in a liquid. By further using
      the finite element method simulations in conjunction with the estimator model, we
      show the existence of three distinct measurement regimes as a function of the
      quality factor of the microcavity. Finally, the estimator model is extended to
      develop a sensing metric to compare performance of optical or non-optical
      sensors. 

PMID- 24104169
TI  - Overcoming Si3N4 film stress limitations for high quality factor ring resonators.
AB  - Silicon nitride (Si3N4) ring resonators are critical for a variety of photonic
      devices. However the intrinsically high film stress of silicon nitride has
      limited both the optical confinement and quality factor (Q) of ring resonators.
      We show that stress in Si3N4 films can be overcome by introducing mechanical
      trenches for isolating photonic devices from propagating cracks. We demonstrate a
      Si3N4 ring resonator with an intrinsic quality factor of 7 million, corresponding
      to a propagation loss of 4.2 dB/m. This is the highest quality factor reported to
      date for high confinement Si3N4 ring resonators in the 1,550 nm wavelength range.

PMID- 24104170
TI  - Expressions for the nonlinear transmission performance of multi-mode optical
      fiber.
AB  - We develop an analytical theory which allows us to identify the information
      spectral density limits of multimode optical fiber transmission systems. Our
      approach takes into account the Kerr-effect induced interactions of the
      propagating spatial modes and derives closed-form expressions for the spectral
      density of the corresponding nonlinear distortion. Experimental characterization
      results have confirmed the accuracy of the proposed models. Application of our
      theory in different FMF transmission scenarios has predicted a ~10% variation in
      total system throughput due to changes associated with inter-mode nonlinear
      interactions, in agreement with an observed 3dB increase in nonlinear noise power
      spectral density for a graded index four LP mode fiber. 

PMID- 24104171
TI  - A performance investigation of correlation-based and pilot-tone-assisted
      frequency offset compensation method for CO-OFDM.
AB  - We carry out a comprehensive analysis to examine the performance of our recently
      proposed correlation-based and pilot-tone-assisted frequency offset compensation
      method in coherent optical OFDM system. The frequency offset is divided into two
      parts: fraction part and integer part relative to the channel spacing. Our
      frequency offset scheme includes the correlation-based Schmidl algorithm for
      fraction part estimation as well as pilot-tone-assisted method for integer part
      estimation. In this paper, we analytically derive the error variance of fraction
      part estimation methods in the presence of laser phase noise using different
      correlation-based algorithms: Schmidl, Cox and Cyclic Prefix based. This
      analytical expression is given for the first time in the literature. Furthermore,
      we give a full derivation for the pilot-tone-assisted integer part estimation
      method using the OFDM model. 

PMID- 24104172
TI  - Multi-channel deep tissue flowmetry based on temporal diffuse speckle contrast
      analysis.
AB  - Recently, diffuse speckle contrast analysis (DSCA) was introduced as a competent
      modality for deep tissue blood flow measurement, where the speckle contrast is
      calculated over spatial domain on the CCD image of diffuse reflectance. In this
      paper, we introduce time-domain DSCA where temporal statistics are used for
      speckle contrast calculation and results in the same deep tissue flow
      measurement. This new modality is especially suitable for multi-channel real-time
      flowmetry, and we demonstrate its performance on human arm during cuff occlusion
      test. Independent component analysis (ICA) study on multi-channel data shows
      promising results about underlying physiology.

PMID- 24104173
TI  - Microwave Photonics: current challenges towards widespread application.
AB  - Microwave Photonics, a symbiotic field of research that brings together the
      worlds of optics and radio frequency is currently facing several challenges in
      its transition from a niche to a truly widespread technology essential to support
      the ever-increasing values for speed, bandwidth, processing capability and
      dynamic range that will be required in next generation hybrid access networks. We
      outline these challenges, which are the subject of the contributions to this
      focus issue. 

PMID- 24104174
TI  - Fiber Bragg gratings for microwave photonics subsystems.
AB  - Microwave photonics (MWP) is an emerging filed in which photonic technologies are
      employed to enable and enhance functionalities in microwave systems which are
      usually very challenging to fulfill directly in the microwave domain. Various
      photonic devices have been used to achieve the functions. A fiber Bragg grating
      (FBG) is one of the key components in microwave photonics systems due to its
      unique features such as flexible spectral characteristics, low loss, light
      weight, compact footprint, and inherent compatibility with other fiber-optic
      devices. In this paper, we discuss the recent development in employing FBGs for
      various microwave photonics subsystems, with an emphasis on subsystems for
      microwave photonic signal processing and microwave arbitrary waveform generation.
      The limitations and potential solutions are also discussed. 

PMID- 24104175
TI  - Faster than fiber: over 100-Gb/s signal delivery in fiber wireless integration
      system.
AB  - We summarize several different approaches for the realization of large capacity
      (>100Gb/s) fiber wireless integration system, including optical polarization
      division-multiplexing (PDM) combined with multiple-input multiple-output (MIMO)
      reception, advanced multi-level modulation, optical multi-carrier modulation,
      electrical multi-carrier modulation, antenna polarization multiplexing and multi
      band multiplexing. These approaches can effectively reduce the signal baud rate
      as well as the required bandwidth for optical and electrical devices. We also
      investigate the problems, such as wireless multi-path effect due to different
      wireless transmission distance, existing in the large capacity fiber wireless
      integration system. We demonstrate these problems can be effectively solved based
      on advanced digital-signal-processing (DSP) algorithms including classic constant
      modulus algorithm (CMA). Moreover, based on the combination of these approaches
      as well as advanced DSP algorithms, we have successfully demonstrated a 400G
      fiber wireless integration system, which creates a capacity record of wireless
      delivery and ushers in a new era of ultra-high bit rate (>400Gb/s) optical
      wireless integration communications at mm-wave frequencies. 

PMID- 24104176
TI  - Photonic generation and independent steering of multiple RF signals for software
      defined radars.
AB  - As the improvement of radar systems claims for digital approaches, photonics is
      becoming a solution for software defined high frequency and high stability signal
      generation. We report on our recent activities on the photonic generation of
      flexible wideband RF signals, extending the proposed architecture to the
      independent optical beamforming of multiple signals. The scheme has been tested
      generating two wideband signals at 10 GHz and 40 GHz, and controlling their
      independent delays at two antenna elements. Thanks to the multiple
      functionalities, the proposed scheme allows to improve the effectiveness of the
      photonic approach, reducing its cost and allowing flexibility, extremely wide
      bandwidth, and high stability.

PMID- 24104177
TI  - Integrable high order UWB pulse photonic generator based on cross phase
      modulation in a SOA-MZI.
AB  - We propose and experimentally demonstrate a potentially integrable optical scheme
      to generate high order UWB pulses. The technique is based on exploiting the cross
      phase modulation generated in an InGaAsP Mach-Zehnder interferometer containing
      integrated semiconductor optical amplifiers, and is also adaptable to different
      pulse modulation formats through an optical processing unit which allows to
      control of the amplitude, polarity and time delay of the generated taps.

PMID- 24104178
TI  - Microwave photonic signal processing.
AB  - Photonic signal processing offers the advantages of large time-bandwidth
      capabilities to overcome inherent electronic limitations. In-fibre signal
      processors are inherently compatible with fibre optic microwave systems that can
      integrate with wireless antennas, and can provide connectivity with in-built
      signal conditioning and electromagnetic interference immunity. Recent methods in
      wideband and adaptive signal processing, which address the challenge of realising
      programmable microwave photonic phase shifters and true-time delay elements for
      phased array beamforming; ultra-wideband Hilbert transformers; single passband,
      widely tunable, and switchable microwave photonic filters; and ultra-wideband
      microwave photonic mixers, are described. In addition, a new microwave photonic
      mixer structure is presented, which is based on using the inherent frequency
      selectivity of the stimulated Brillouin scattering loss spectrum to suppress the
      carrier of a dual-phase modulated optical signal. Results for the new microwave
      photonic mixer demonstrate an extremely wide bandwidth operation of 0.2 to 20 GHz
      and a large conversion efficiency improvement compared to the conventional
      microwave photonic mixer. 

PMID- 24104179
TI  - Silicon nitride microwave photonic circuits.
AB  - We present an overview of several microwave photonic processing functionalities
      based on combinations of Mach-Zehnder and ring resonator filters using the high
      index contrast silicon nitride (TriPleXTM) waveguide technology. All
      functionalities are built using the same basic building blocks, namely straight
      waveguides, phase tuning elements and directional couplers. We recall previously
      shown measurements on high spurious free dynamic range microwave photonic (MWP)
      link, ultra-wideband pulse generation, instantaneous frequency measurements,
      Hilbert transformers, microwave polarization networks and demonstrate new
      measurements and functionalities on a 16 channel optical beamforming network and
      modulation format transformer as well as an outlook on future microwave photonic
      platform integration, which will lead to a significantly reduced footprint and
      thereby enables the path to commercially viable MWP systems.

PMID- 24104180
TI  - Silicon photonics-wireless interface ICs for micro-/millimeter-wave fiber
      wireless networks.
AB  - We present two types of Si photonics-wireless interface (PWI) integrated circuits
      (ICs) realized in standard Si technology. Our PWI ICs convert optical signals
      into radio-frequency (RF) signals for downlink remote antenna units in fiber
      wireless networks. Characterization and modeling of Si avalanche photodetectors
      (APDs) fabricated in two different Si technologies are carried out and used for
      PWI IC design. A 5-GHz RF-over-fiber PWI IC composed of APD, preamplifier, and
      power amplifier (PA) is fabricated in 0.18-MUm CMOS technology and its
      performance is verified by 54-Mb/s wireless local area network data transmission.
      A 60-GHz baseband-over-fiber PWI IC containing APD, baseband photoreceiver, 60
      GHz binary phase-shift keying (BPSK) modulator, and 60-GHz PA is realized in 0.25
      MUm SiGe BiCMOS technology. Error-free transmission of 1.6-Gb/s BPSK data in 60
      GHz with this PWI IC is successfully achieved.

PMID- 24104181
TI  - Photonic synthesis of high fidelity microwave arbitrary waveforms using near
      field frequency to time mapping.
AB  - Photonic radio-frequency (RF) arbitrary waveform generation (AWG) based on
      spectral shaping and frequency-to-time mapping has received substantial
      attention. This technique, however, is critically constrained by the far-field
      condition which imposes strict limits on the complexity of the generated
      waveforms. The time bandwidth product (TBWP) decreases as the inverse of the RF
      bandwidth which limits one from exploiting the full TBWP available from modern
      pulse shapers. Here we introduce a new RF-AWG technique which we call near-field
      frequency-to-time mapping. This approach overcomes the previous restrictions by
      predistorting the amplitude and phase of the spectrally shaped optical signal to
      achieve high fidelity waveforms with radically increased TBWP in the near field
      region.

PMID- 24104182
TI  - Coherent terahertz photonics.
AB  - We present a review of recent developments in THz coherent systems based on
      photonic local oscillators. We show that such techniques can enable the creation
      of highly coherent, thus highly sensitive, systems for frequencies ranging from
      100 GHz to 5 THz, within an energy efficient integrated platform. We suggest that
      such systems could enable the THz spectrum to realize its full applications
      potential. To demonstrate how photonics-enabled THz systems can be realized, we
      review the performance of key components, show recent demonstrations of
      integrated platforms, and give examples of applications.

PMID- 24104183
TI  - Advanced radio over fiber network technologies.
AB  - The evolution of wireless communication networks supporting emerging broadband
      services and applications offers new opportunities for realizing integrated
      optical and wireless network infrastructures. We report on some of our recent
      activities investigating advanced technologies for next generation converged
      optical wireless networks. Developments in Active Antenna Systems, mobile
      fronthaul architectures, and 60 GHz fiber distributed wireless networks are
      described. We also discuss the potential for analog radio over fiber distribution
      links as a viable solution for meeting the capacity requirements of new network
      architectures. 

PMID- 24104184
TI  - Multi-conformation dynamic pharmacophore modeling of the peroxisome proliferator
      activated receptor gamma for the discovery of novel agonists.
AB  - Activation of the peroxisome proliferator-activated receptor gamma (PPARgamma) is
      important for the treatment of type 2 diabetes and obesity through the regulation
      of glucose metabolism and fatty acid accumulation. Hence, the discovery of novel
      PPARgamma agonists is necessary to overcome these diseases. In this study, a
      newly developed approach, multi-conformation dynamic pharmacophore modeling
      (MCDPM), was used for screening candidate compounds that can properly bind
      PPARgamma. Highly populated structures obtained from molecular dynamics (MD)
      simulations were selected by clustering analysis. Based on these structures,
      pharmacophore models were generated from the ligand-binding pocket and then
      validated to check the rationality. Consequently, two hits were retrieved as
      final candidates by utilizing virtual screening and molecular docking
      simulations. These compounds can be used in the design of novel PPARgamma
      agonists. 

PMID- 24104185
TI  - The RNA-binding protein FPA regulates flg22-triggered defense responses and
      transcription factor activity by alternative polyadenylation.
AB  - RNA-binding proteins (RBPs) play an important role in plant host-microbe
      interactions. In this study, we show that the plant RBP known as FPA, which
      regulates 3'-end mRNA polyadenylation, negatively regulates basal resistance to
      bacterial pathogen Pseudomonas syringae in Arabidopsis. A custom microarray
      analysis reveals that flg22, a peptide derived from bacterial flagellins, induces
      expression of alternatively polyadenylated isoforms of mRNA encoding the defence
      related transcriptional repressor ETHYLENE RESPONSE FACTOR 4 (ERF4), which is
      regulated by FPA. Flg22 induces expression of a novel isoform of ERF4 that lacks
      the ERF-associated amphiphilic repression (EAR) motif, while FPA inhibits this
      induction. The EAR-lacking isoform of ERF4 acts as a transcriptional activator in
      vivo and suppresses the flg22-dependent reactive oxygen species burst. We propose
      that FPA controls use of proximal polyadenylation sites of ERF4, which
      quantitatively limit the defence response output. 

PMID- 24104186
TI  - A review of peripheral biomarkers in major depression: the potential of
      inflammatory and oxidative stress biomarkers.
AB  - Biomarkers are regularly used in medicine to provide objective indicators of
      normal biological processes, pathogenic processes or pharmacological responses to
      therapeutic interventions, and have proved invaluable in expanding our
      understanding and treatment of medical diseases. In the field of psychiatry,
      assessment and treatment has, however, primarily relied on patient interviews and
      questionnaires for diagnostic and treatment purposes. Biomarkers in psychiatry
      present a promising addition to advance the diagnosis, treatment and prevention
      of psychiatric diseases. This review provides a summary on the potential of
      peripheral biomarkers in major depression with a specific emphasis on those
      related to inflammatory/immune and oxidative stress/antioxidant defences. The
      complexities associated with biomarker assessment are reviewed specifically
      around their collection, analysis and interpretation. Focus is placed on the
      potential of peripheral biomarkers to aid diagnosis, predict treatment response,
      enhance treatment-matching, and prevent the onset or relapse of major depression.

PMID- 24104187
TI  - Sympathetic axonopathies and hyperinnervation in the small intestine smooth
      muscle of aged Fischer 344 rats.
AB  - It is well documented that the intrinsic enteric nervous system of the
      gastrointestinal (GI) tract sustains neuronal losses and reorganizes as it ages.
      In contrast, age-related remodeling of the extrinsic sympathetic projections to
      the wall of the gut is poorly characterized. The present experiment, therefore,
      surveyed the sympathetic projections to the aged small intestine for
      axonopathies. Furthermore, the experiment evaluated the specific prediction that
      catecholaminergic inputs undergo hyperplastic changes. Jejunal tissue was
      collected from 3-, 8-, 16-, and 24-month-old male Fischer 344 rats, prepared as
      whole mounts consisting of the muscularis, and processed immunohistochemically
      for tyrosine hydroxylase, the enzymatic marker for norepinephrine, and either the
      protein CD163 or the protein MHCII, both phenotypical markers for macrophages.
      Four distinctive sympathetic axonopathy profiles occurred in the small intestine
      of the aged rat: (1) swollen and dystrophic terminals, (2) tangled axons, (3)
      discrete hyperinnervated loci in the smooth muscle wall, including at the bases
      of Peyer's patches, and (4) ectopic hyperplastic or hyperinnervating axons in the
      serosa/subserosal layers. In many cases, the axonopathies occurred at localized
      and limited foci, involving only a few axon terminals, in a pattern consistent
      with incidences of focal ischemic, vascular, or traumatic insult. The present
      observations underscore the complexity of the processes of aging on the neural
      circuitry of the gut, with age-related GI functional impairments likely
      reflecting a constellation of adjustments that range from selective neuronal
      losses, through accumulation of cellular debris, to hyperplasias and
      hyperinnervation of sympathetic inputs. 

PMID- 24104188
TI  - Phosphatidylserine index as a marker of the procoagulant phenotype of acute
      myelogenous leukemia cells.
AB  - Patients with acute myelogenous leukemia (AML) are at risk for thrombotic
      complications. Risk to develop thrombosis is closely tied to leukemia subtype,
      and studies have shown an association between leukocytosis and thrombosis in AML
      M3. We evaluated the relative roles of cell count and the surface expression of
      tissue factor (TF) and phosphatidylserine (PS) in the procoagulant phenotype of
      AML cell lines. The TF-positive AML M3 cell lines, NB4 and HL60, and AML M2 cell
      line, AML14, exhibited both extrinsic tenase and prothrombinase activity in a
      purified system and promoted experimental thrombus formation. In contrast, the TF
      negative AML cell line, HEL, exhibited only prothrombinase activity and did not
      affect the rate of occlusive thrombus formation. In plasma, NB4, HL60 and AML14
      shortened clotting times in a cell-count, PS- and TF-dependent manner. Exposure
      of cultured NB4, HL60, and AML14 cells to the chemotherapeutic agent daunorubicin
      increased their extrinsic tenase activity and PS expression. Clot initiation time
      inversely correlated with logarithm of PS index, defined as the product of
      multiplying leukocyte count with cell surface PS exposure. We propose that
      leukemia cell PS index may serve as a biomarker for procoagulant activity. 

PMID- 24104189
TI  - [Knowledge, attitudes, and practices relative to the risk of transmission of
      hepatitis B and C viruses in a hospital in Togo].
AB  - OBJECTIVE: To assess the knowledge, the attitudes, and the practices of hospital
      nursing staff in relation to the infectious risks of the hepatitis B and C
      viruses. METHODS: Cross-sectional descriptive survey conducted at the Lome Campus
      Teaching Hospital among the nursing staff present during at least one of the 2
      consecutive workdays of the survey. RESULTS: The total nursing staff included 190
      people, 115 (60.5%) of whom participated in the investigation. Slightly more than
      three-fifths were men (61.7%). Their mean age was 37.9 +/- 10.7 years. The
      contaminated materials encountered most often were blood (94.8%), needle-drawn
      fluids (77.4%), and biopsy samples (53.9%). Staff most often did not comply with
      protective measures: 75.5% did not use gloves regularly and 46.0% did not use
      bibs. More than one third of the nursing staff (34.8%) had had such a needle
      stick or related accident, but only 8.8% had reported them: 74.2% because of the
      potential administrative difficulties and 25.8% because of ignorance (25.8%).
      Staff knowledge about the means of transmission of these viruses was good
      (98.3%). The vaccination coverage rate of the nurses questioned was 51.3%.
      CONCLUSION: Training and awareness campaigns about the occupational risks of HBV
      and HCV remain necessary.

PMID- 24104191
TI  - Dilution of urine drug tests: is it random?
AB  - BACKGROUND: The purpose of this study was to determine whether the act of in vivo
      urine dilution is a random phenomenon. METHODS: The sample population was divided
      into 4 groups for each of the drugs tested. The groups are precreatinine
      normalization laboratory positive, precreatinine normalization laboratory
      negative, and postcreatinine normalization laboratory drug positive, and
      postcreatinine normalization laboratory drug negative. The nonparametric Kruskal
      Wallis 1-way ANOVA by ranks with post hoc Mann-Whitney U testing Bonferroni
      adjustment was used to compare the mean urine creatinine concentration of each
      group. RESULTS: The Kruskal-Wallis test revealed that each drug had a
      statistically significant difference in group comparisons. Post hoc testing found
      that cocaine demonstrated no statistically significant difference between the
      prenormalization drug positive and negative groups. Amphetamines, marijuana, and
      opiates did confirm statistically significant differences between the
      prenormalization drug positive and negative groups. The examination of
      phencyclidine was limited by the lack of a prenormalization drug positive group;
      therefore, no definitive findings can be presented. Statistically significant
      differences were found between the postnormalization drug positive and negative
      groups for each drug tested. CONCLUSIONS: This study supports the theory that
      urine dilution is not a random happening and it may adversely affect the
      integrity of the drug-testing process.

PMID- 24104192
TI  - Magnetic exchange coupling of a synthetic Co(II)-complex to a ferromagnetic Ni
      substrate.
AB  - On-surface assembly of a spin-bearing and non-aromatic porphyrin-related
      synthetic Co(II)-complex on a ferromagnetic Ni thin film substrate and subsequent
      magnetic exchange interaction across the interface were studied by scanning
      tunnelling microscopy (STM), X-ray absorption spectroscopy (XAS), X-ray magnetic
      circular dichroism (XMCD) and density functional theory +U (DFT + U)
      calculations.

PMID- 24104190
TI  - Increased incidence of cardiovascular conditions among older adults with
      pathological gambling features in a prospective study.
AB  - OBJECTIVES: To evaluate the prospective associations between at
      risk/problem/pathological gambling (ARPG) and incident medical conditions among
      older adults. METHODS: Secondary data analysis of the National Epidemiologic
      Survey on Alcohol and Related Conditions, waves 1 and 2, collected from 2001 to
      2002 and 2004 to 2005, respectively. Participants are adults aged 55 years and
      older (n = 10,231) who were selected from a nationally representative community
      sample of adults residing in the United States. Past-year diagnostic criteria for
      pathological gambling at wave 1 were evaluated with the Alcohol Use Disorder and
      Associated Disabilities Interview Schedule-Diagnostic and Statistical Manual of
      Mental Disorders-Fourth Edition. Physical health conditions were assessed at wave
      1 and wave 2. Logistic regression modeling was conducted on groups categorized as
      ARPG (participants endorsing 1 or more inclusionary criteria for pathological
      gambling) and non-ARPG (nongambling/low-frequency gambling or gambling without
      endorsement of pathological gambling criteria). RESULTS: Relative to non-ARPG,
      ARPG is prospectively associated with elevated incidences of arteriosclerosis and
      any heart condition, independently of wave-1 sociodemographic characteristics,
      psychiatric comorbidity, substance use, and body mass index. CONCLUSIONS: Older
      adults who demonstrate risky or problematic levels of gambling may be at
      particular risk for the onset of some physical health conditions. Individuals
      with at-risk/problem/pathological gambling features should be monitored more
      closely for the development of these conditions and encouraged to adopt
      activities that confer health benefits. Efforts should be made to educate older
      adults and their caretakers on the adverse incident physical health conditions
      associated with ARPG.

PMID- 24104193
TI  - Alpinetin inhibits LPS-induced inflammatory mediator response by activating PPAR
      gamma in THP-1-derived macrophages.
AB  - Alpinetin, a novel plant flavonoid derived from Alpinia katsumadai Hayata, has
      been reported to have anti-inflammatory properties. However, the anti
      inflammatory mechanism of alpinetin has not been fully elucidated. The purpose of
      this study was to investigate the anti-inflammatory mechanism of alpinetin in
      modifying lipopolysaccharide (LPS)-induced signaling pathways in human THP-1
      macrophages. The cells were stimulated with LPS in the presence or absence of
      alpinetin. The pro-inflammatory cytokines were evaluated by ELISA and qRT-PCR.
      Toll-like receptor 4 (TLR4), nuclear factor-kappaB (NF-kappaB), inhibitory kappa
      B (IkappaBalpha) protein, p38, extracellular signal-regulated kinase (ERK), c-Jun
      N-terminal kinase (JNK) and PPAR-gamma were determined by Western blotting. The
      results showed that alpinetin inhibited TNF-alpha, IL-6 and IL-1beta expression
      in LPS-stimulated human THP-1 macrophages in a dose-dependent manner. Western
      blot analysis showed that alpinetin suppressed LPS-induced NF-kappaB activation,
      IkappaBalpha degradation, phosphorylation of ERK, JNK and P38. Furthermore,
      alpinetin could significantly down-regulated the expression of TLR4 stimulating
      by LPS. We also found that alpinetin could activate PPAR-gamma and the anti
      inflammatory effects of alpinetin can be reversed by GW9662, a specific
      antagonist for PPAR-gamma. These results suggest that alpinetin activates PPAR
      gamma, thereby attenuating TLR4 expression and TLR4 mediated NF-kappaB and MAPK
      activation and the release of pro-inflammatory cytokines. These findings suggest
      that alpinetin may be a therapeutic agent against inflammatory diseases.

PMID- 24104194
TI  - A comparison of methods for quantifying training load: relationships between
      modelled and actual training responses.
AB  - PURPOSE: To assess the validity of methods for quantifying training load, fitness
      and fatigue in endurance athletes using a mathematical model. METHODS: Seven
      trained runners (VO2max: 51.7 +/- 4.5 mL kg(-1) min(-1), age: 38.6 +/- 9.4 years,
      mean +/- SD) completed 15 weeks of endurance running training. Training sessions
      were assessed using a heart rate (HR), running pace and rating of perceived
      exertion (RPE). Training dose was calculated using the session-RPE method,
      Banisters TRIMP and the running training stress score (rTSS). Weekly running
      performance (1,500-m time trial), fitness (submaximal HR, resting HR) and fatigue
      [profile of mood states, heart rate variability (HRV)] were measured. A
      mathematical model was applied to the training data from each runner to provide
      individual estimates of performance, fitness and fatigue. Correlations assessed
      the relationships between the modelled and actual weekly performance, fitness and
      fatigue measures within each runner. RESULTS: Training resulted in 5.4 +/- 2.6 %
      improvement in 1,500-m performance. Modelled performance was correlated with
      actual performance in each subject, with relationships being r = 0.70 +/- 0.11,
      0.60 +/- 0.10 and 0.65 +/- 0.13 for the rTSS, session-RPE and TRIMP input
      methods, respectively. There were moderate correlations between modelled and
      actual fitness (submaximal HR) for the session-RPE (-0.43 +/- 0.37) and TRIMP (
      0.48 +/- 0.39) methods and moderate-to-large correlations between modelled and
      actual fatigue measured through HRV indices for both session-RPE (-0.48 +/- 0.39)
      and TRIMP (-0.59 +/- 0.31) methods. CONCLUSIONS: These findings showed that each
      of the training load methods investigated are appropriate for quantifying
      endurance training dose and that submaximal HR and HRV may be useful for
      monitoring fitness and fatigue, respectively.

PMID- 24104195
TI  - Anticoagulation management in nonvalvular atrial fibrillation: current and future
      directions.
AB  - Oral anticoagulant therapy, either with vitamin K antagonists (VKAs) or with
      novel oral anticoagulants such as dabigatran, rivaroxaban, and apixaban, is the
      mainstay for thromboprophylaxis in patients with atrial fibrillation (AF).
      Thromboembolic risk factors associated with AF and risk factors for bleeding
      associated with oral anticoagulant therapy are largely the same, and bleeding
      risk very rarely outweighs individual benefit of thrombosis prevention, thus
      resulting in positive net clinical benefit of oral anticoagulant therapy in
      almost all AF patients. Prevention of AF-related thromboembolic events most
      commonly requires long-term oral anticoagulant therapy. Over time, various
      clinical situations may occur in a given patient (e.g., a need for an urgent
      surgery or invasive intervention, acute stroke, etc.), which may require a
      temporary or permanent modification of anticoagulant therapy regardless of which
      anticoagulant drug has been used. This may be particularly challenging for
      physicians because many issues regarding optimal use of oral anticoagulant drugs
      in specific clinical situations still remain to be solved. In this review
      article, we discuss the periprocedural management of oral anticoagulant therapy,
      bridging, transition to another oral anticoagulant, the occurrence of acute
      stroke in a patient already taking an oral anticoagulant, and decision when it is
      safe to resume oral anticoagulation therapy after stroke. We summarize the
      available evidence and current (and future) approaches to oral anticoagulation
      management in such clinical situations. 

PMID- 24104196
TI  - Essential role of the cytochrome P450 enzyme CYP2A5 in olfactory mucosal toxicity
      of naphthalene.
AB  - Naphthalene (NA), a ubiquitous environmental pollutant that can cause pulmonary
      and nasal toxicity in laboratory animals, requires cytochrome P450 (P450)
      mediated metabolic activation to cause toxicity. Our recent study using a Cyp2f2
      null mouse showed that CYP2F2 plays an essential role in NA-induced lung
      toxicity, but not in NA-induced nasal toxicity. The aim of this study was to
      determine whether mouse CYP2A5, abundantly expressed in nasal olfactory mucosa
      (OM) and the liver, but less in the lung, plays a major role in the bioactivation
      and toxicity of NA in the OM. We found, by comparing Cyp2a5-null and wild-type
      (WT) mice, that the loss of CYP2A5 expression led to substantial decreases in
      rates of NA metabolic activation by OM microsomes. The loss of CYP2A5 did not
      cause changes in systemic clearance of NA (at 200 mg/kg, i.p.). However, the
      Cyp2a5-null mice were much more resistant than were WT mice to NA-induced nasal
      toxicity (although not lung toxicity), when examined at 24 hours after NA dosing
      (at 200 mg/kg, i.p.), or to NA-induced depletion of total nonprotein sulfhydryl
      in the OM (although not in the lung), examined at 2 hours after dosing. Thus,
      mouse CYP2A5 plays an essential role in the bioactivation and toxicity of NA in
      the OM, but not in the lung. Our findings further illustrate the tissue-specific
      nature of the role of individual P450 enzymes in xenobiotic toxicity, and provide
      the basis for a more reliable assessment of the potential risks of NA nasal
      toxicity in humans. 

PMID- 24104198
TI  - Evaluation and mechanistic analysis of the cytotoxicity of the acyl glucuronide
      of nonsteroidal anti-inflammatory drugs.
AB  - The chemical reactivity of acyl glucuronide (AG) has been thought to be
      associated with the toxic properties of drugs containing carboxylic acid
      moieties, but there has been no direct evidence showing that AG formation is
      related to the observed toxicity. In the present study, the cytotoxicity of AGs,
      especially that associated with the inflammatory response, was investigated. The
      changes in the mRNA and protein expression levels of interleukin 8 (IL-8) and
      monocyte chemoattractant protein (MCP)-1 induced by the treatment of human
      peripheral blood mononuclear cells (PBMCs) with diclofenac (Dic), probenecid
      (Pro), tolmetin (Tol), ibuprofen (Ibu), naproxen (Nap), and their AGs were
      investigated by real-time reverse transcription polymerase chain reaction, and
      the viabilities of CD3+, CD14+, and CD19+ cells were measured by flow cytometry.
      Treatment with Dic-AG, Pro-AG, and Tol-AG significantly increased the expression
      levels of IL-8 and MCP-1. In addition, Dic-AG, Pro-AG, and Tol-AG significantly
      decreased the viability of CD14+ cells. Of these three AGs, Dic-AG showed the
      most potent changes, followed by Tol-AG and Pro-AG. Treatment with Ibu-AG and Nap
      AG affected neither the expression levels of IL-8 and MCP-1 nor the viability of
      CD14+ cells. None of the drugs affected the CD3+ and CD19+ cell populations. Dic
      AG increased the phosphorylation of p38 mitogen-activated protein (MAP) kinase
      and c-Jun N-terminal kinase (JNK)1/2. The pretreatment of peripheral blood
      mononuclear cells (PBMCs) with SB203580 (p38 inhibitor) significantly suppressed
      the Dic-AG-induced expression of inflammatory factors and cytotoxicity of CD14+
      cells. In conclusion, AGs induce inflammatory responses and cytotoxicity against
      CD14+ cells via the p38 MAPK pathway. These factors may be useful biomarkers for
      evaluating the toxicity of AGs. 

PMID- 24104197
TI  - Candidate gene polymorphisms in patients with acetaminophen-induced acute liver
      failure.
AB  - Acetaminophen is a leading cause of acute liver failure (ALF). Genetic
      differences might predispose some individuals to develop ALF. In this exploratory
      study, we evaluated genotype frequency differences among patients enrolled by the
      ALF Study Group who had developed ALF either intentionally from a single-time
      point overdose of acetaminophen (n = 78), unintentionally after chronic high
      doses of acetaminophen (n = 79), or from causes other than acetaminophen (n =
      103). The polymorphisms evaluated included those in genes encoding putative
      acetaminophen-metabolizing enzymes (UGT1A1, UGT1A6, UGT1A9, UGT2B15, SULT1A1,
      CYP2E1, and CYP3A5) as well as CD44 and BHMT1. Individuals carrying the CYP3A5
      rs776746 A allele were overrepresented among ALF patients who had intentionally
      overdosed with acetaminophen, with an odds ratio of 2.3 (95% confidence interval,
      1.1-4.9; P = 0.034) compared with all other ALF patients. This finding is
      consistent with the enhanced bioactivation of acetaminophen by the CYP3A5 enzyme.
      Persons homozygous for the CD44 rs1467558 A allele were also overrepresented
      among patients who had unintentionally developed ALF from chronic acetaminophen
      use, with an odds ratio of 4.0 (1.0-17.2, P = 0.045) compared with all other ALF
      subjects. This finding confirms a prior study that found elevated serum liver
      enzyme levels in healthy volunteers with the CD44 rs1467558 AA genotype who had
      consumed high doses of acetaminophen for up to 2 weeks. However, both genetic
      associations were considered relatively weak, and they were not statistically
      significant after adjustment for multiple comparisons testing. Nevertheless, both
      CYP3A5 rs776746 and CD44 rs1467558 warrant further investigation as potential
      genomic markers of enhanced risk of acetaminophen-induced ALF. 

PMID- 24104200
TI  - Vitamin D Therapy and Cardiac Function in Chronic Kidney Disease-Reply.

PMID- 24104199
TI  - MicroRNA-561 promotes acetaminophen-induced hepatotoxicity in HepG2 cells and
      primary human hepatocytes through downregulation of the nuclear receptor
      corepressor dosage-sensitive sex-reversal adrenal hypoplasia congenital critical
      region on the X chromosome, gene 1 (DAX-1).
AB  - One of the major mechanisms involved in acetaminophen (APAP)-induced
      hepatotoxicity is hepatocyte nuclear factor 4alpha (HNF4alpha)-mediated
      activation of pregnane X receptor (PXR) and constitutive androstane receptor
      (CAR). In the present study, we investigated the role of miR-561 and its target
      gene DAX-1 encoding a corepressor of HNF4alpha in the process of APAP-induced
      hepatotoxicity. We used both human hepatocellular liver carcinoma cell line
      (HepG2) cells and primary human hepatocytes in this study and monitored the
      levels of reactive oxygen species, lactate dehydrogenase, and glutathione. Our
      bioinformatics study suggests an association between miR-561 and DAX-1, but not
      HNF4alpha. Treatment of HepG2 cells with APAP significantly reduced the
      expression of DAX-1 in a concentration-dependent manner. miR-561 was induced by
      APAP treatment in HepG2 cells. Transfection of HepG2 cells with an miR-561 mimic
      exacerbated APAP-induced hepatotoxicity. HNF4alpha is physically associated with
      DAX-1 in HepG2 cells. A decreased protein level of DAX-1 by APAP treatment was
      also enhanced by miR-561 mimic transfection in HepG2 cells and primary human
      hepatocytes. The basal and APAP-induced expression of PXR and CAR was enhanced by
      miR-561 mimic transfection; however, transfection of HepG2 cells or primary human
      hepatocytes with a miR-561 inhibitor or DAX-1 small interfering RNA reversed
      these effects. Additionally, the chromatin immunoprecipitation assay revealed
      that recruitment of DAX-1 onto the PXR promoter was inversely correlated with the
      recruitment of peroxisome proliferator-activated receptor-alpha coactivator
      1alpha and HNF4alpha on APAP treatment. These results indicate that miR-561
      worsens APAP-induced hepatotoxicity via inhibition of DAX-1 and consequent
      transactivation of nuclear receptors. 

PMID- 24104201
TI  - Molecular degradation of ancient documents revealed by 1H HR-MAS NMR
      spectroscopy.
AB  - For centuries mankind has stored its knowledge on paper, a remarkable biomaterial
      made of natural cellulose fibers. However, spontaneous cellulose degradation
      phenomena weaken and discolorate paper over time. The detailed knowledge of
      products arising from cellulose degradation is essential in understanding
      deterioration pathways and in improving durability of cultural heritage. In this
      study, for the first time, products of cellulose degradation were individually
      detected in solid paper samples by means of an extremely powerful proton HR-MAS
      NMR set-up, in combination to a wise use of both ancient and, as reference,
      artificially aged paper samples. Carboxylic acids, in addition to more complex
      dicarboxylic and hydroxy-carboxylic acids, were found in all samples studied.
      Since these products can catalyze further degradation, their knowledge is
      fundamental to improve conservation strategies of historical documents.
      Furthermore, the identification of compounds used in ancient production
      techniques, also suggests for artifacts dating, authentication and provenance. 

PMID- 24104203
TI  - Detection of PCV-2 DNA in stool samples from infants vaccinated with RotaTeq(r).
AB  - Rotarix(r) and RotaTeq(r) vaccines have led to a dramatic reduction in rotavirus
      disease worldwide. However, the detection of porcine circovirus type 1 (PCV-1)
      and 2 (PCV-2) DNA in these vaccines raised some safety concerns. Studies
      examining shedding of rotavirus in stool from rotavirus vaccine recipients have
      been performed but no published data exist regarding the shedding of PCV virus in
      stools of vaccinees. The goal of this study was to determine if PCV-1 and/or PCV
      2 is shed in the feces of infants vaccinated with RotaTeq(r). Using multiple PCR
      assays for detection of PCV DNA, we tested for PCV-1 and PCV-2 in 826 stool swab
      samples collected serially during the first 9 d after vaccination from 102
      children vaccinated with RotaTeq(r). Since the vaccine is recommended and uptake
      is high, we did not have samples from unvaccinated infants. A total of 235
      (28.5%) samples from 59 vaccine recipients were positive for PCV-2 DNA by one or
      more assays used in this study. PCV-1 DNA was not detected in RotaTeq(r) or any
      of the stool swab extracts. Twenty-two of the 102 vaccine recipients (21.6%) shed
      RotaTeq(r) vaccine strain and 10 of these vaccinees (9.8%) were shedding both PCV
      DNA and rotavirus vaccine RNA. PCV DNA was detected up to 9 d post vaccination
      and was most frequently detected in the first 5 d after vaccination. This study
      demonstrated shedding of PCV-2 DNA by RotaTeq(r) vaccinees but we did not find
      evidence that this DNA was associated with viable PCV. Findings from this study
      support the continued use of current rotavirus vaccines.

PMID- 24104204
TI  - Characterization of genome-wide transcriptional changes in liver and adipose
      tissues of ZDF (fa/fa) rats fed R-alpha-lipoic acid by next-generation
      sequencing.
AB  - We report on the characterization of lipogenic tissue transcriptional networks
      that support physiological responses of obese rats to a lipid-lowering bioactive
      food compound, R-alpha-lipoic acid (LA). Nine-week-old male Zucker diabetic fatty
      (fa/fa) rats were fed a chow diet supplemented with 3 g LA per kg diet or pair
      fed for 2 wk. At the end of the trial, high-quality RNA was extracted from the
      liver and epididymal fat and subjected to transcriptome analysis by RNA-Seq
      technology. Results showed a substantially higher number of differentially
      expressed genes [DEG, false discovery rate adjusted P <= 0.05 and absolute log2
      (fold change) >= 1] in the liver (110 genes) vs. epididymal fat (10 genes). Most
      epididymal fat DEG were also differentially expressed in liver and shared
      directionality of change. Gene Ontology (GO) analysis of these transcripts
      revealed significant enrichment of GO categories related to immune response,
      stress response, lipid metabolism, and carboxylic acid metabolic processes. Of
      interest, interferon-related genes involved in defense against microorganisms and
      innate immune response were induced by LA. Lipid metabolism-related transcript
      changes observed in LA-fed animals included downregulation of lipogenic genes
      (Pnpla3, Pnpla5, Elovl6, Acly, Gpam, and Aacs) and concomitant upregulation of
      short-, medium-, and long-chain fatty acid metabolic processes (Acot1, Acot2,
      Acsf2, and Crat). Transcriptional changes were accompanied by the lowering of
      abdominal adiposity and blood triacylglycerol levels. We conclude that LA dietary
      supplementation induces prominent gene expression changes in liver in support of
      significant improvement of whole-body lipid status.

PMID- 24104205
TI  - Reducing milking frequency during nutrient restriction has no effect on the
      hepatic transcriptome of lactating dairy cattle.
AB  - The objective of this study was to investigate if a reduced milking frequency
      altered the effect of dietary energy restriction on the hepatic transcriptome of
      grazing dairy cows during early lactation. Multiparous Holstein-Friesian and
      Holstein-Friesian * Jersey cows (n = 120) were milked twice daily (2*) from
      calving until 34 +/- 6 days in milk (mean +/- SD). Cows were then allocated to
      one of four treatments in a 2 * 2 factorial arrangement. Treatments consisted of
      two milking frequencies [2* or once daily (1*)] and two feeding levels for 3 wk:
      adequately fed (AF) or underfed (UF, 60% of AF). Liver tissue was biopsied from
      12 cows per treatment after 3 wk of treatment, and the hepatic transcriptome was
      profiled with an Agilent 4 * 44k bovine microarray. Over 2,900 genes were
      differentially expressed in response to the energy restriction; however, no
      effects resulted from changes to milking frequency. This may indicate that after
      3 wk of 1* milking, any changes to the liver transcriptome that may have occurred
      earlier have returned to normal. After 3 wk of energy restriction, gene
      expression patterns indicate that glucose-sparing pathways were activated, and
      gluconeogenesis was increased in UF cows. Genes involved in hepatic stress were
      upregulated in response to the energy restriction indicative of the pressure
      energy restriction places on liver function. Other pathways upregulated included
      "cytoskeletal remodeling," indicating that a 3 wk energy restriction resulted in
      molecular changes to assist tissue remodeling. Overall, 1* milking does not
      modify the hepatic transcriptome changes that occur in response to an energy
      restriction.

PMID- 24104206
TI  - Primary care professional's perspectives on treatment decision making for
      depression with African Americans and Latinos in primary care practice.
AB  - Increasing interest has been shown in shared decision making (SDM) to improve
      mental health care communication between underserved immigrant minorities and
      their providers. Nonetheless, very little is known about this process. The
      following is a qualitative study of fifteen primary care providers at two
      Federally Qualified Health Centers in New York and their experience during
      depression treatment decision making. Respondents described a process
      characterized in between shared and paternalistic models of treatment decision
      making. Barriers to SDM included discordant models of illness, stigma, varying
      role expectations and decision readiness. Respondents reported strategies used to
      overcome barriers including understanding illness perceptions and the role of the
      community in the treatment process, dispelling stigma using cultural terms,
      orienting patients to treatment and remaining available regarding the treatment
      decision. Findings from this study have implications for planning SDM
      interventions to guide primary care providers through treatment engagement for
      depression. 

PMID- 24104208
TI  - Impact of an online survivorship primer on clinician knowledge and intended
      practice changes.
AB  - The number of adult cancer survivors in the USA is expected to double by the year
      2050. A call for increased survivorship care and provider training came from the
      Institute of Medicine (IOM) in the form of a landmark report in 2006. A shortage
      of physicians complicates the burden of survivorship care. The purpose of this
      effort was to design, develop, and evaluate a fully accredited, evidence-based
      continuing medical education (CME) and continuing education (CE) intervention to
      address the established knowledge gap for breast cancer, prostate cancer,
      colorectal cancer, and non-Hodgkin lymphoma survivorship education. Delivered
      through the Medscape Education (WebMD) platform, the course covered epidemiology,
      survivor issues, and currently available guidelines using illustrative patient
      cases. Knowledge gain was evaluated using a pretest-posttest design. Program
      evaluation was assessed by survey. Additional areas examined included post
      intervention inquiry regarding expected changes to clinical practice. The results
      of this educational intervention demonstrated the effectiveness of internet-based
      CME/CE for cancer survivorship. Learning gain was significant (p < 0.0005).
      Effect size (d = 1.71) suggested extremely high practical significance, as the
      difference between the means was larger than 1 standard deviation. Significant
      knowledge gains were observed for each survivorship knowledge question across all
      clinical specialties studied. Nearly 100% of participants agreed that the course
      contributed to survivorship care and was organized effectively. Participants
      reported that the course was designed effectively (97.2%), and 68.1% responded in
      favor of adopting alternative communication strategies with patients and families
      upon completion of the course.

PMID- 24104209
TI  - Restoration of the coagulation cascade on CPB: a case report.
AB  - Coagulopathy can sometimes be observed when CPB times are prolonged. Correction
      of coagulopathy post CPB can present the surgical team with a number of
      challenges, including right ventricular volume overload, hemodilution, anemia and
      excessive cell salvage with further loss of coagulation factors. Restoration of
      the coagulation cascade on CPB may help to avoid these issues. This case report
      is of a 64-year-old male with a delayed diagnosis of aortic dissection. The
      patient presented to the cardiac surgery operating room with hepatic and renal
      shock/failure, with the resulting coagulopathy. The described technique is
      representative of a technique that we sometimes employ to restore the clotting
      mechanism before separating from bypass. 

PMID- 24104211
TI  - Elastic behavior of a red blood cell with the membrane's nonuniform natural
      state: equilibrium shape, motion transition under shear flow, and elongation
      during tank-treading motion.
AB  - Direct numerical simulations of the mechanics of a single red blood cell (RBC)
      were performed by considering the nonuniform natural state of the elastic
      membrane. A RBC was modeled as an incompressible viscous fluid encapsulated by an
      elastic membrane. The in-plane shear and area dilatation deformations of the
      membrane were modeled by Skalak constitutive equation, while out-of-plane bending
      deformation was formulated by the spring model. The natural state of the membrane
      with respect to in-plane shear deformation was modeled as a sphere ([Formula: see
      text]), biconcave disk shape ([Formula: see text]) and their intermediate shapes
      ([Formula: see text]) with the nonuniformity parameter [Formula: see text], while
      the natural state with respect to out-of-plane bending deformation was modeled as
      a flat plane. According to the numerical simulations, at an experimentally
      measured in-plane shear modulus of [Formula: see text] and an out-of-plane
      bending rigidity of [Formula: see text] of the cell membrane, the following
      results were obtained. (i) The RBC shape at equilibrium was biconcave discoid for
      [Formula: see text] and cupped otherwise; (ii) the experimentally measured fluid
      shear stress at the transition between tumbling and tank-treading motions under
      shear flow was reproduced for [Formula: see text]; (iii) the elongation
      deformation of the RBC during tank-treading motion from the simulation was
      consistent with that from in vitro experiments, irrespective of the [Formula: see
      text] value. Based on our RBC modeling, the three phenomena (i), (ii), and (iii)
      were mechanically consistent for [Formula: see text]. The condition [Formula: see
      text] precludes a biconcave discoid shape at equilibrium (i); however, it gives
      appropriate fluid shear stress at the motion transition under shear flow (ii),
      suggesting that a combined effect of [Formula: see text] and the natural state
      with respect to out-of-plane bending deformation is necessary for understanding
      details of the RBC mechanics at equilibrium. Our numerical results demonstrate
      that moderate nonuniformity in a membrane's natural state with respect to in
      plane shear deformation plays a key role in RBC mechanics. 

PMID- 24104214
TI  - Effect of abiotic stress stimuli on S-nitrosoglutathione reductase in plants.
AB  - S-nitrosylation of protein cysteine thiol groups has recently emerged as a
      widespread and important reversible post-translational protein modification,
      involved in redox signalling pathways of nitric oxide and reactive nitrogen
      species. S-nitrosoglutathione reductase (GSNOR), member of class III alcohol
      dehydrogenase family (EC 1.1.1.1), is considered the key enzyme in the catabolism
      of major low molecular S-nitrosothiol, S-nitrosoglutathione, and hence to control
      the level of protein S-nitrosylation. Changes of GSNOR activity after exposure to
      different abiotic stress conditions, including low and high temperature,
      continuous dark and de-etiolation, and mechanical injury, were investigated in
      important agricultural plants. Significantly higher GSNOR activity was found
      under normal conditions in leaves of Cucumis spp. genotype sensitive to
      biotrophic pathogen Golovinomyces cichoracearum. GSNOR activity was generally
      increased in all studied plants by all types of stress conditions. Strong down
      regulation of GSNOR was observed in hypocotyls of etiolated pea plants, which did
      not recover to values of green plants even 168 h after the transfer of etiolated
      plants to normal light regime. These results point to important role of GSNOR
      during normal plant development and in plant responses to several types of
      abiotic stress conditions. 

PMID- 24104216
TI  - Sensing with magnetic dipolar resonances in semiconductor nanospheres.
AB  - In this work we propose two novel sensing principles of detection that exploit
      the magnetic dipolar Mie resonance in high-refractive-index dielectric
      nanospheres. In particular, we theoretically investigate the spectral evolution
      of the extinction and scattering cross sections of these nanospheres as a
      function of the refractive index of the external medium (next). Unlike resonances
      in plasmonic nanospheres, the spectral position of magnetic resonances in high
      refractive-index nanospheres barely shifts as next changes. Nevertheless, there
      is a drastic reduction in the extinction cross section of the nanospheres when
      next increases, especially in the magnetic dipolar spectral region, which is
      accompanied with remarkable variations in the radiation patterns. Thanks to these
      changes, we propose two new sensing parameters, which are based on the detection
      of: i) the intensity variations in the transmitted or backscattered radiation by
      the dielectric nanospheres at the magnetic dipole resonant frequency, and ii) the
      changes in the radiation pattern at the frequency that satisfies Kerker's
      condition of near-zero forward radiation. To optimize the sensitivity, we
      consider several semiconductor materials and particles sizes.

PMID- 24104210
TI  - Using human induced pluripotent stem cells to treat retinal disease.
AB  - The eye is an ideal target for exploiting the potential of human induced
      pluripotent stem cell (hiPSC) technology in order to understand disease pathways
      and explore novel therapeutic strategies for inherited retinal disease. The aim
      of this article is to map the pathway from state-of-the art laboratory-based
      discoveries to realising the translational potential of this emerging technique.
      We describe the relevance and routes to establishing hiPSCs in selected models of
      human retinal disease. Additionally, we define pathways for applying hiPSC
      technology in treating currently incurable, progressive and blinding retinal
      disease. 

PMID- 24104215
TI  - Predictors of prolonged length of intensive care unit stay after stage I
      palliation: a report from the National Pediatric Cardiology Quality Improvement
      Collaborative.
AB  - The objective of this study is to identify predictors of prolonged intensive care
      unit (ICU) length of stay (LOS) for single ventricle patients following Stage I
      palliation. We hypothesize that peri-operative factors contribute to prolonged
      ICU stay among children with hypoplastic left heart syndrome (HLHS) and its
      variants. In 2008, as a part of the Joint Council on Congenital Heart Disease
      initiative, the National Pediatric Cardiology-Quality Improvement Collaborative
      established a data registry for patients with HLHS and its variants undergoing
      staged palliation. Between July 2008 and August 2011, 33 sites across the United
      States submitted discharge data essential to this analysis. Data describing the
      patients, their procedures, and their hospital experience were entered. LOS
      estimates were generated. Prolonged LOS in the ICU was defined as stay greater
      than or equal to 26 days (i.e., 75th percentile). Statistical analyses were
      carried out to identify pre-operative, operative, and post-operative predictors
      of prolonged LOS in the ICU. The number of patients with complete discharge data
      was 303, and these subjects were included in the analysis. Univariate and
      multivariate analyses were performed. Multivariate analysis revealed that lower
      number of enrolled participants (e.g., 1-10) per site, the presence of pre
      operative acidosis, increased circulatory arrest time, the occurrence of a
      central line infection, and the development of respiratory insufficiency
      requiring re-intubation were associated with prolonged LOS in the ICU. Prolonged
      LOS in the ICU following Stage I palliation in patients with HLHS and HLHS
      variant anatomy is associated with site enrollment, circulatory arrest time, pre
      operative acidosis, and some post-operative complications, including central line
      infection and re-intubation. Further study of these associations may reveal
      strategies for reducing LOS in the ICU following the Norwood and Norwood-variant
      surgeries.

PMID- 24104217
TI  - Crossed fiber optic Bessel beams for curvilinear optofluidic transport of
      dielectric particles.
AB  - Due to its unique non-diffracting and self-reconstructing nature, Bessel beams
      have been successfully adopted to trap multiple particles along the beam's axial
      direction. However, prior bulk-optic based Bessel beams have a fundamental form
      factor limitation for in situ, in-vitro, and in-vivo applications. Here we
      present a novel implementation of Fourier optics along a single strand of hybrid
      optical fiber in a monolithic manner that can generate pseudo Bessel beam arrays
      in two-dimensional space. We successfully demonstrate unique optofluidic
      transport of the trapped dielectric particles along a curvilinear optical route
      by multiplexing the fiber optic pseudo Bessel beams. The proposed technique can
      form a new building block to realize reconfigurable optofluidic transportation of
      particulates that can break the limitations of both prior bulk-optic Bessel beam
      generation techniques and conventional microfluidic channels.

PMID- 24104218
TI  - Electrically driven green, olivine, and amber color nanopyramid light emitting
      diodes.
AB  - We report the fabrication and studies of electrically driven green, olivine, and
      amber color nanopyramid GaN light emitting diodes (LEDs). InGaN/GaN multiple
      quantum wells (MQWs) were grown on the nanopyramid semipolar facets. Compared
      with the commonly used (0001) c-plane MQWs, the semipolar facet has lower
      piezoelectric field, resulting in much faster radiative recombination efficiency.
      This is important for high In content MQWs. The measured internal quantum
      efficiencies for green, olivine, and amber color LED are 30%, 25%, and 21%,
      respectively. The radiative and non-radiative lifetime of the semipolar MQWs are
      also investigated.

PMID- 24104219
TI  - Design of plasmonic nano-antenna for total internal reflection fluorescence
      microscopy.
AB  - We propose a gold modified bow-tie plasmonic nano-antenna, which can be suitably
      used in combination with total internal reflection fluorescence microscopy. The
      plasmonic nano-antenna, supporting well-separated multiple resonances, not only
      concentrates the total internal reflection evanescent field at the deep
      subwavelength scale, but also enhances fluorescence emission by the Purcell
      effect. Finite-difference time-domain computations show that the enhancement of
      the excitation light strongly correlates with the far-field radiation pattern
      radiated from the antenna. Depending on the antenna geometry, the resonant modes
      are widely tuned and their wavelengths can be easily matched to the diverse
      emission or excitation wavelengths of fluorophores.

PMID- 24104220
TI  - Colorless monolithically integrated 120 degrees  downconverter.
AB  - We numerically demonstrate colorless reception of dense wavelength division
      multiplexed channels in the C-band for high-order QAM (16-64 QAM) signals on a
      120 degrees  monolithically integrated downconverter, based on a 2x3 MMI with
      calibrated analog IQ recovery. It is shown that the proposed calibrated 120
      degrees  downconverter can increase up to 80 the number of coincident channels in
      an efficient way, exhibiting good signal dynamic range and high fabrication
      yield. As this downconverter makes use of the minimum number of power outputs
      required for perfect recovery of IQ signals, it becomes an interesting
      alternative to conventional 90 degrees  based downconverters.

PMID- 24104221
TI  - Adaptive pulse oximeter with dual-wavelength based on wavelet transforms.
AB  - Pulse oximeter is widely used in the monitoring of blood oxygen in clinic for its
      convenience and efficiency. However, synchronizing light source flashing with
      data collecting is required, otherwise the separation of the data from different
      LEDs will fail. More importantly, synchronous acquisition makes the pulse
      oximetry system vulnerable. Meanwhile, the pulse waveform extraction is a crucial
      procedure in the measurement. Hence, in this paper, an asynchronous acquisition
      pulse oximetry system based on wavelet transform has been built.
      PhotoPlethysmoGraph (PPG) and photoelectric detection technology are applied in
      our homemade system. The adaptive soft-threshold de-noising is realized by
      Stein's Unbiased Risk Estimate (SURE). The principle and system configuration are
      described. The preliminary experiment results from wavelet transforms and Fourier
      transforms are compared. The results show that our homemade system is adaptive,
      accurate, robust and simple.

PMID- 24104222
TI  - Fast full-color computational imaging with single-pixel detectors.
AB  - Single-pixel detectors can be used as imaging devices by making use of structured
      illumination. These systems work by correlating a changing incident light field
      with signals measured on a photodiode to derive an image of an object. In this
      work we demonstrate a system that utilizes a digital light projector to
      illuminate a scene with approximately 1300 different light patterns every second
      and correlate these with the back scattered light measured by three spectrally
      filtered single-pixel photodetectors to produce a full-color high-quality image
      in a few seconds of data acquisition. We utilize a differential light projection
      method to self normalize the measured signals, improving the reconstruction
      quality whilst making the system robust to external sources of noise. This
      technique can readily be extended for imaging applications at non-visible
      wavebands. 

PMID- 24104223
TI  - Semianalytical estimation of the four-wave mixing noise based on extreme value
      theory.
AB  - Four-wave mixing (FWM) is one the limiting factors for existing and future
      wavelength division multiplexed optical networks. A semianalytical method based
      on Monte Carlo and Extreme Value theory is proposed and applied to study the
      influence of the FWM noise on the performance of WDM systems. The statistical
      behavior of the FWM noise is investigated while the Bit-Error rate is calculated
      for various combinations of the design parameters and for both single and
      multiple span WDM systems. The semianalytical method is also compared to the
      Multicanonical Monte Carlo (MCMC) method showing the same efficiency and accuracy
      with the former providing however the advantage of deriving closed-form
      approximations for the cumulative distribution functions of the photocurrents in
      the mark and the space state and the BER.

PMID- 24104224
TI  - Modification of electric and magnetic dipole emission in anisotropic plasmonic
      systems.
AB  - In order to investigate the effects of plasmonic environments on spontaneous
      emission of magnetic and electric dipoles, we have studied luminescence of Eu3+
      ions in close vicinity to gold nanostrip arrays. Significant changes in the
      emission kinetics, emission polarization, and radiation patterns have been
      observed in the wavelength range corresponding to the plasmonic resonance. The
      effect of the plasmonic resonance on the magnetic dipole transition 5D0-->7F1 is
      found to be very different from its effect on the electric dipole transitions.
      This makes Eu3+- containing complexes promising for mapping local distributions
      of magnetic and electric fields in metamaterials and plasmonic systems.

PMID- 24104225
TI  - Nanoplasmonic surfaces enabling strong surface-normal electric field enhancement.
AB  - Conventional two-dimensional (2D) plasmonic arrays provide electric field
      intensity enhancement in the plane, typically with a surface coverage around 50%
      in the plan-view. Here, we show nanoplasmonic three-dimensional (3D) surfaces
      with 100% surface coverage enabling strong surface-normal field enhancement.
      Experimental measurements are found to agree well with the full electromagnetic
      solution. Along with the surface-normal localization when using the plasmonic 3D
      surface, observed maximum field enhancement is 7.2-fold stronger in the 3D
      surface than that of the 2D counterpart structure. 3D-plasmonic nonplanar
      surfaces provide the ability to generate volumetric field enhancement, possibly
      useful for enhanced plasmonic coupling and interactions.

PMID- 24104226
TI  - A simple photonic generation of linearly chirped microwave pulse with large time
      bandwidth product and high compression ratio.
AB  - Based on the heterodyne beating between the pre-chirped optical pulse and the
      continuous wave (CW) light in a wideband photodetector (PD), linearly chirped
      microwave pulse with time duration of 3.2ns and bandwidth of 33GHz, which yields
      a large time-bandwidth product (TBWP) of 106 and high compression ratio of 160,
      is generated in our experiment. Dispersion compensation fiber (DCF) with uniform
      response across broad bandwidth is used for providing the original linear chirp
      in our method, which shows the promise to generate linearly chirped microwave
      pulse with bandwidth of up to THz. The flexibility of the center frequency and
      the stability of the time-frequency performance are demonstrated by generating
      different types of linearly chirped microwave pulses. The range resolution of our
      generated microwave pulse is also verified by off-line processing.

PMID- 24104227
TI  - Distance estimation using a single computational camera with dual off-axis color
      filtered apertures.
AB  - In this paper, we present a novel computational imaging system using a dual off
      axis color filtered aperture (DCA) for distance estimation in a single-camera
      framework. The DCA consists of two off-axis apertures that are covered by red and
      cyan color filters. The two apertures generate misaligned color channels in which
      the amount of misalignment of points in the image plane are a function of the
      distance from the camera of the corresponding points in the object plane. The
      primary contribution of this paper is the derivation of a mathematical model of
      the relationship between the color shifting values and distance of an object from
      the camera when the camera parameters and the baseline distance between the two
      apertures in the DCA are given. The proposed computational imaging system can be
      implemented simply by inserting an appropriately sized DCA into any general
      optical system. Experimental results show that the DCA camera is able to estimate
      the distances of objects within a single-camera framework.

PMID- 24104228
TI  - Non-exponential spontaneous emission dynamics for emitters in a time-dependent
      optical cavity.
AB  - We have theoretically studied the effect of deterministic temporal control of
      spontaneous emission in a dynamic optical microcavity. We propose a new paradigm
      in light emission: we envision an ensemble of two-level emitters in an
      environment where the local density of optical states is modified on a time scale
      shorter than the decay time. A rate equation model is developed for the excited
      state population of two-level emitters in a time-dependent environment in the
      weak coupling regime in quantum electrodynamics. As a realistic experimental
      system, we consider emitters in a semiconductor microcavity that is switched by
      free-carrier excitation. We demonstrate that a short temporal increase of the
      radiative decay rate depletes the excited state and drastically increases the
      emission intensity during the switch time. The resulting time-dependent
      spontaneous emission shows a distribution of photon arrival times that strongly
      deviates from the usual exponential decay: A deterministic burst of photons is
      spontaneously emitted during the switch event. 

PMID- 24104229
TI  - Characterization and reduction of spectral distortions in silicon-on-insulator
      integrated Bragg gratings.
AB  - A major issue in the fabrication of integrated Bragg grating filters in highly
      confined waveguides is the average effective index fluctuations caused by
      waveguide dimension variations. Lateral variations are caused by the sidewall
      roughness created during the etching process while vertical variations are coming
      from the wafer silicon layer thickness non-uniformity. Grating spectral
      distortions are known to result solely from the low spatial frequency components
      of these variations. As a result, in this work, we present an experimental method
      to quantify such relevant spatial components by stitching a hundred high
      resolution scanning electron microscope images. Additionally, we propose two
      techniques to reduce, in the design, the phase noise impact on integrated Bragg
      gratings without relying on fabrication process improvements. More specifically,
      we show that the use of hybrid multimode/singlemode waveguides reduce by more
      than one order of magnitude the effect of sidewall roughness on integrated Bragg
      gratings while we show that the fabrication of ultra-compact gratings in spiral
      waveguides mitigate the impact of the silicon layer thickness variations.

PMID- 24104231
TI  - High-speed height measurement by a light-source-stepping method using a linear
      LED array.
AB  - High-speed height measurement is required in industrial fields for analyzing the
      behavior of a breaking object, a vibrating object or a rotating object. A shape
      measurement performed using a phase-shifting method can measure the shape with
      high spatial resolution because the coordinates can be obtained pixel by pixel. A
      light-source-stepping method (LSSM) that uses a linear LED array by means of a
      whole-space tabulation method (WSTM) has been proposed. Accurate shape
      measurement can be performed using this method. The response speed of the LED
      array is greater than 12 kHz. In this paper, height measurement is performed
      using WSTM and LSSM with a linear LED array and a high-speed camera. It was
      verified that the response speed of the linear LED is greater than 200 kHz. The
      phase shifting was performed at 12 kHz, and the height measurement of the
      vibrating woofer was performed at 4 kHz using a 3-step phase-shifting method.

PMID- 24104230
TI  - All-optical osteotomy to create windows for transcranial imaging in mice.
AB  - Surgical procedures as a prelude to optical imaging are a rate-limiting step in
      experimental neuroscience. Towards automation of these procedures, we describe
      the use of nonlinear optical techniques to create a thinned skull window for
      transcranial imaging. Metrology by second harmonic generation was used to map the
      surfaces of the skull and define a cutting path. Plasma-mediated laser ablation
      was utilized to cut bone. Mice prepared with these techniques were used to image
      subsurface cortical vasculature and blood flow. The viability of the brain tissue
      was confirmed via histological analysis and supports the utility of solely
      optical techniques for osteotomy and potentially other surgical procedures. 

PMID- 24104232
TI  - Scattering and absorption from strongly anisotropic nanoparticles.
AB  - Strongly anisotropic particles with hyperbolic dispersion that are small compared
      with the wavelength show strong resonance in the near infrared. The unique
      resonance modes are insensitive to the host refractive index and independent of
      particle size. In addition, the far-field direction of scattering does not depend
      on incident angle. Because the strength of resonance is comparable to a plasmonic
      nanoparticle in the visible region, a hyperbolic-dispersed particle is a
      promising scatterer as well as local heater in the near infrared. 

PMID- 24104233
TI  - Bright broadband coherent fiber sources emitting strongly blue-shifted resonant
      dispersive wave pulses.
AB  - We predict and realize the targeted wavelength conversion from the 1550-nm band
      of a fs Er:fiber laser to an isolated band inside 370-850 nm, corresponding to a
      blue-shift of 700-1180 nm. The conversion utilizes resonant dispersive wave
      generation in widely available optical fibers with good efficiency (~7%). The
      converted band has a large pulse energy (~1 nJ), high spectral brightness (~1
      mW/nm), and broad Gaussian-like spectrum compressible to clean transform-limited
      ~17 fs pulses. The corresponding coherent fiber sources open up portable
      applications of optical parametric oscillators and dual-output synchronized
      ultrafast lasers. 

PMID- 24104234
TI  - Study of the distributed thermal lens of LD end pumped rectangular gain.
AB  - In the LD end pumped rectangular laser gain medium, the thermal induced
      refractive index is not only non-uniformly transversely, but also non-uniformly
      and distributed along the pumping beam propagation, the effect of thermal lens is
      a distributed not a lumped lens effect as previously considered. In this paper,
      the effect of a distributed thermal lens is analyzed. 

PMID- 24104235
TI  - Frequency-domain acquisition of fourth-order correlation by spectral intensity
      interferometry.
AB  - We report on the spectral intensity interferometer (SII) which is a frequency
      domain variant of the fourth-order interferometry. In the SII, the power spectrum
      of the intensity is acquired for light fields of an interferometer. It produces a
      fringed spectral interferogram which can be acquired by means of an electric
      spectrum analyzer in keeping the relative time delay constant during the
      acquisition. Through both theoretical and experimental investigations, we have
      found that the SII interferogram provides the intensity correlation information
      without concern of field-sensitive disturbances which are vulnerable to minute
      variations of the optical paths. As an application example, a precision time-of
      flight measurement was demonstrated by using a fiber-optic SII with an amplified
      spontaneous emission (ASE) light source. A large delay of 4.1-km long fiber was
      successfully analyzed from the fringe period. Its wavelength-dependent group
      delay or the group velocity dispersion (GVD) was also measured from the phase
      shift of the cosine fringe with a sub-picosecond delay precision.

PMID- 24104236
TI  - Inverse design of the absorbing layer for detection enhancement in near-infrared
      range.
AB  - In spite of rapidly increasing demand and various applications of infrared (IR)
      detectors, their design process for the performance improvement has been mostly
      dependent on researchers' intuition and knowledge. We present two-dimensional
      unit structure design of the absorbing layer in IR detectors. A systematic
      approach is introduced to enhance the absorbing efficiency of incident beam in
      the near-infrared wavelength range. We derived a layered structure composed of a
      silicon nitride (Si3N4) layer and an amorphous silicon (a-Si) one in turn by the
      so called topology optimization in association with the time variant finite
      element analysis (FEA). It is confirmed that thickness at each layer is in
      associated with the IR wavelength so that detail dimensions of each layer are
      inferred. A prototype of the layered structure was fabricated and its performance
      has been verified through experimental measurement.

PMID- 24104237
TI  - Modeling electro-optical characteristics of broad area semiconductor lasers based
      on a quasi-stationary multimode analysis.
AB  - To increase the brightness of broad area laser diodes, it is necessary to tailor
      the optical properties of their waveguide region. For this purpose, there is the
      need for simulation tools which can predict the optical properties of the
      complete device and thus of the outcoupled light. In the present publication, we
      show a numerical method to calculate typical intensity distributions of the
      multimode beam inside a high-power semiconductor laser. The model considers
      effects of mode competition and the influence of the gain medium on the optical
      field. Simulation results show a good agreement with near and far field
      measurements of the analyzed broad area laser diodes.

PMID- 24104238
TI  - Entanglement distribution over 300 km of fiber.
AB  - We report the distribution of time-bin entangled photon pairs over 300 km of
      optical fiber. We realized this by using a high-speed and high signal-to-noise
      ratio entanglement generation/evaluation setup that consists of periodically
      poled lithium niobate waveguides and superconducting single photon detectors. The
      observed two-photon interference fringes exhibited a visibility of 84%. We
      confirmed the violation of Bell's inequality by 2.9 standard deviations. 

PMID- 24104239
TI  - Top-hat beam output of a single-mode microstructured optical fiber: impact of
      core index depression.
AB  - A new strategy to obtain a single-mode fiber with a flattened intensity profile
      distribution is presented. It is based on the use of an OVD-made high index ring
      deposited on a silica rod having a refractive index slightly lower than the
      silica used for the microstructured cladding. Using this strategy, we realized
      the first single-mode fiber with a quasi-perfect top-hat intensity profile around
      1 um. Numerical studies clearly demonstrate the advantage of using a core index
      depression to insure the single-mode operation of the fiber at the working
      wavelength.

PMID- 24104240
TI  - Mid-infrared Raman-soliton continuum pumped by a nanotube-mode-locked sub
      picosecond Tm-doped MOPFA.
AB  - We demonstrate a mid-infrared Raman-soliton continuum extending from 1.9 to 3 um
      in a highly germanium-doped silica-clad fiber, pumped by a nanotube mode-locked
      thulium-doped fiber system, delivering 12 kW sub-picosecond pulses at 1.95 um.
      This simple and robust source of light covers a portion of the atmospheric
      transmission window.

PMID- 24104241
TI  - Light absorption in hybrid silicon-on-insulator/quantum dot waveguides.
AB  - We analyze the absorption coefficient of planarized silicon-on-insulator
      waveguides coated by close packed mono- and multilayers of colloidal PbS/CdS
      quantum dots (QDs). Experimental data clearly show the influence of the QDs on
      the waveguide absorbance around 1500 nm, where we find that QDs absorb stronger
      in thicker layers. To simulate the absorption coefficient of QD functionalized
      waveguides, the QD layer is replaced by an effective medium with a dielectric
      function determined by dipolar coupling between neighbouring QDs. Using the host
      dielectric constant epsilonh as an adjustable parameter, excellent agreement with
      the experimental results is obtained. In this way, the increase in absorption
      cross section with layer thickness can be traced back to an increasing epsilonh.
      We argue that this reflects the decreasing influence of the surroundings on the
      epsilonh, which therefore evolves from an extrinsic property for monolayers to a
      more intrinsic film property for multilayers.

PMID- 24104242
TI  - Si3N4 ring resonator-based microwave photonic notch filter with an ultrahigh peak
      rejection.
AB  - We report a simple technique in microwave photonic (MWP) signal processing that
      allows the use of an optical filter with a shallow notch to exhibit a microwave
      notch filter with anomalously high rejection level. We implement this technique
      using a low-loss, tunable Si3N4 optical ring resonator as the optical filter, and
      achieved an MWP notch filter with an ultra-high peak rejection > 60 dB, a tunable
      high resolution bandwidth of 247-840 MHz, and notch frequency tuning of 2-8 GHz.
      To our knowledge, this is a record combined peak rejection and resolution for an
      integrated MWP filter.

PMID- 24104243
TI  - Differential receivers with highly -uniform MSM Germanium photodetectors capped
      by SiGe layer.
AB  - Waveguide integrated MSM (metal-semiconductor-metal) Germanium (Ge)
      photodetectors (PDs) with a SiGe capping layer were exploited for silicon
      photonics integration. Under optimized epitaxial growth conditions, the capping
      layer passivated the Ge surface, resulting in sufficiently low dark current of
      the PDs. In addition, the PDs exhibited a narrower distribution of the dark
      current than PDs with a Si capping layer, probably due to the lower surface
      leakage current. Low-noise differential receivers with uniform MSM Ge PDs
      exhibiting 10 Gbps data transmission were realized.

PMID- 24104244
TI  - Robust destriping method with unidirectional total variation and framelet
      regularization.
AB  - Multidetector imaging systems often suffer from the problem of stripe noise and
      random noise, which greatly degrade the imaging quality. In this paper, we
      propose a variational destriping method that combines unidirectional total
      variation and framelet regularization. Total-variation-based regularizations are
      considered effective in removing different kinds of stripe noise, and framelet
      regularization can efficiently preserve the detail information. In essence, these
      two regularizations are complementary to each other. Moreover, the proposed
      method can also efficiently suppress random noise. The split Bregman iteration
      method is employed to solve the resulting minimization problem. Comparative
      results demonstrate that the proposed method significantly outperforms state-of
      the-art destriping methods on both qualitative and quantitative assessments.

PMID- 24104246
TI  - Demonstration of a vertical pin Ge-on-Si photo-detector on a wet-etched Si
      recess.
AB  - In this paper, we demonstrate a vertical pin Ge-on-Si photo-detector on a wet
      etched Si recess on a SOI wafer. A 120 nm-deep Si recess is etched on the SOI
      wafer with a 340 nm-thick top Si layer by the TMAH solution. The measured results
      show that the responsivity is more than 0.60 A/W for TE polarization and is more
      than 0.65 A/W for TM polarization at 1550 nm wavelength. Compared to the photo
      detector without the Si recess, the responsivities for both TE and TM
      polarizations are improved by ~10%. A low dark current of 170 nA is achieved at a
      bias voltage of -1 V. And, the 3 dB-bandwidth at a bias voltage of -3 V is 21.5
      GHz. This approach can be used to improve the coupling and absorption for high
      responsivity of photo-detector while maintain its high speed on a thick SOI
      platform based on the simulation results.

PMID- 24104247
TI  - A full ellipsometric approach to optical sensing with Bloch surface waves on
      photonic crystals.
AB  - We report on the investigation on the resolution of optical sensors exploiting
      Bloch surface waves sustained by one dimensional photonic crystals. A figure of
      merit is introduced to quantitatively assess the performance of such sensors and
      its dependency on the geometry and materials of the photonic crystal. We show
      that the figure of merit and the resolution can be improved by adopting a full
      ellipsometric phase-sensitive approach. The theoretical predictions are confirmed
      by experiments in which, for the first time, such type of sensors are operated in
      the full ellipsometric scheme. 

PMID- 24104248
TI  - Phase retrieval for object and probe using a series of defocus near-field images.
AB  - Full field x-ray propagation imaging can be severely deteriorated by wave front
      aberrations. Here we present an extension of ptychographic phase retrieval with
      simultaneous probe and object reconstruction suitable for the near-field
      diffractive imaging setting. Update equations used to iteratively solve the phase
      problem from a set of near-field images in view of reconstruction both object and
      probe are derived. The algorithm is tested based on numerical simulations
      including photon shot noise. The results indicate that the approach provides an
      efficient way to overcome restrictive idealizations of the illumination wave in
      the near-field (propagation) imaging.

PMID- 24104249
TI  - Direct generation of broadband chaos by a monolithic integrated semiconductor
      laser chip.
AB  - A solitary monolithic integrated semiconductor laser (MISL) chip with a size of
      780 micrometer is designed and fabricated for broadband chaos generation. Such a
      MISL chip consists of a DFB section, a phase section and an amplification
      section. Test results indicate that under suitable operation conditions, this
      laser chip can be driven into broadband chaos. The generated chaos covers an RF
      frequency range, limited by our measurement device, of 26.5GHz, and possesses
      significant dimension and complexity. Moreover, the routes into and out of chaos
      are also characterized through extracting variety dynamical states of temporal
      waveforms, phase portraits, RF spectra and statistical indicators.

PMID- 24104250
TI  - Directly phase-modulation-mode-locked doubly-resonant optical parametric
      oscillator.
AB  - We present results on direct mode-locking of a doubly-resonant optical parametric
      oscillator (DRO) using an electro-optic phase modulator with low resonant
      frequency of 80 MHz as the single mode-locking element. Pumped by a cw laser at
      532 nm and based on MgO:sPPLT as the nonlinear material, the DRO generates 533 ps
      pulses at 80 MHz and 471 ps pulses at 160 MHz. Stable train of mode-locked pulses
      is obtained at a modulation depth of 1.83 radians when the modulation frequency
      is precisely tuned and the cavity length is carefully adjusted. The effects of
      frequency detuning, modulation depth, input laser pump power, crystal temperature
      and position of modulator inside the cavity, on pulse duration and repetition
      rate have been studied. Operating at degeneracy, under mode-locked condition, the
      signal-idler spectrum exhibits a bandwidth of ~31 nm, and the spectrum has been
      investigated for different phase-matching temperatures. Mode-locked operation has
      been confirmed by second-harmonic-generation of the DRO output in a beta-BaB2O4
      crystal, where a 4 times enhancement in green power is observed compared to cw
      operation.

PMID- 24104251
TI  - Silicon nitride based plasmonic components for CMOS back-end-of-line integration.
AB  - Silicon nitride waveguides provide low propagation loss but weak mode confinement
      due to the relatively small refractive index contrast between the Si3N4 core and
      the SiO2 cladding. On the other hand, metal-insulator-metal (MIM) plasmonic
      waveguides offer strong mode confinement but large propagation loss. In this
      work, MIM-like plasmonic waveguides and passive devices based on horizontal Cu
      Si3N4-Cu or Cu-SiO2-Si3N4-SiO2-Cu structures are integrated in the conventional
      Si3N4 waveguide circuits using standard CMOS backend processes, and are
      characterized around 1550-nm telecom wavelengths using the conventional fiber
      waveguide-fiber method. The Cu-Si3N4(~100 nm)-Cu devices exhibit ~0.78-dB/MUm
      propagation loss for straight waveguides, ~38% coupling efficiency with the
      conventional 1-MUm-wide Si3N4 waveguide through a 2-MUm-long taper coupler, ~0.2
      dB bending loss for sharp 90 degrees  bends, and ~0.1-dB excess loss for
      ultracompact 1 * 2 and 1 * 4 power splitters. Inserting a ~10-nm SiO2 layer
      between the Si3N4 core and the Cu cover (i.e., the Cu-SiO2(~10 nm)-Si3N4(~100 nm)
      SiO2(~10 nm)-Cu devices), the propagation loss and the coupling efficiency are
      improved to ~0.37 dB/MUm and ~52% while the bending loss and the excess loss are
      degraded to ~3.2 dB and ~2.1 dB, respectively. These experimental results are
      roughly consistent with the numerical simulation results after taking the
      influence of possible imperfect fabrication into account. Ultracompact plasmonic
      ring resonators with 1-MUm radius are demonstrated with an extinction ratio of
      ~18 dB and a quality factor of ~84, close to the theoretical prediction.

PMID- 24104252
TI  - Intrinsic photocurrent characteristics of graphene photodetectors passivated with
      Al2O3.
AB  - The intrinsic photo-response of chemical vapor deposited (CVD) graphene
      photodetectors were investigated after eliminating the influence of
      photodesorption using an atomic layer deposited (ALD) Al2O3 passivation layer. A
      general model describing the intrinsic photocurrent generation in a graphene is
      developed using the relationship between the device dimensions and the level of
      intrinsic photocurrent under UV illumination.

PMID- 24104253
TI  - Two-photon quantum interference in integrated multi-mode interference devices.
AB  - Multi-mode interference (MMI) devices fabricated in silicon oxynitride (SiON)
      with a refractive index contrast of 2.4% provide a highly compact and stable
      platform for multi-photon non-classical interference. MMI devices can introduce
      which-path information for photons propagating in the multi-mode section which
      can result in degradation of this non-classical interference. We theoretically
      derive the visibility of quantum interference of two photons injected in a MMI
      device and predict near unity visibility for compact SiON devices. We complement
      the theoretical results by experimentally demonstrating visibilities of up to
      97.7% in 2*2 MMI devices without the requirement of narrow-band photons.

PMID- 24104255
TI  - Tunable and stable UV-NIR photoluminescence from annealed SiOx with Si
      nanoparticles.
AB  - We demonstrate stable and tunable light emission in ultraviolet to near infrared
      regime by using annealed SiOx sample. By adjusting the ratio of Si and O of SiOx,
      different wavelengths such as ultraviolet, visible and near infrared
      photoluminescence can be tuned. From the results of transmission electron
      microscope, various sizes (1~4 nm) of the embedded Si nanoparticles were formed.
      Nanoparticles with smaller sizes were indeed formed for UV-blue emitting samples
      and the origin of light emission may be misattributed to the quantum confinement
      effects. However, we found the efficient and stable light emission in UV-blue
      regime, with lifetime on the order of nanoseconds, is dominantly from the
      defects.

PMID- 24104254
TI  - Low-voltage, high speed, compact silicon modulator for BPSK modulation.
AB  - A low voltage, high speed, compact silicon Mach-Zehnder Interferometer (MZI)
      modulator for Binary Phase Shift Keying (BPSK) modulation has been demonstrated.
      High modulation efficiency, VpiLpi equals to 0.45V.cm, was obtained in a 1mm
      length device owing to a higher doping concentration and low-loss traveling-wave
      electrode. 25 Gb/s non-return-to-zero(NRZ)-BPSK with 6Vpp RF driving signal was
      achieved. Driven by a very low 3Vpp RF signal, the 10 Gb/s NRZ-BPSK was also
      realized benefiting from the high modulation efficiency and the low-voltage
      driving scheme. The power consumption for the BPSK modulation was as low as 0.118
      W. These results prove that the silicon modulator is suitable for advanced
      communication system with low power consumption.

PMID- 24104256
TI  - Spectroscopic properties and diode end-pumped 2.79 MUm laser performance of
      Er,Pr:GYSGG crystal.
AB  - We demonstrate a 968 nm diode end-pumped Er,Pr:GYSGG (Gd1.17Y1.83Sc2Ga3O12) laser
      at 2.79 MUm operated in the pulse and continuous-wave (CW) modes. The lifetimes
      for the upper laser level 4I11/ 2 and lower level 4I13/2 are 0.52 and 0.60 ms,
      respectively. The laser produces 284 mW of power in the CW mode, corresponding to
      the optical-to-optical efficiency of 14.8% and slope efficiency of 17.4%. The
      maximum laser energy achieved is 2.4 mJ at a repetition rate of 50 Hz and pulse
      duration of 0.5 ms, corresponding to a peak power of 4.8 W and slope efficiency
      of 18.3%. These results suggest that doping deactivator Pr3+ ions can effectively
      decrease the lower-level lifetime and improve the laser efficiency.

PMID- 24104257
TI  - Intermodulation distortion suppression for intensity-modulated analog fiber-optic
      link incorporating optical carrier band processing.
AB  - An intermodulation distortion suppression method based on the optical carrier
      band processing is demonstrated. A systematic analysis of the main optical
      spectrum contributors for the third-order intermodulation distortion in the
      nonlinear system is presented. Theoretical analysis shows that the third-order
      intermodulation distortion terms can cancel each other if a proper phase shifting
      is imposed to the optical carrier band. We experimentally demonstrate the
      approach with a two-tone test and a suppression of about 33 dB in the third-order
      intermodulation distortion is obtained. Experimental results show that an overall
      fundamental to third-order intermodulation distortion ratio of up to 64 dB is
      achieved and the link dynamic range is improved by 14.7 dB, compared with the
      conventional link without the proposed optical carrier band processing. 

PMID- 24104259
TI  - Demonstration of a wavelength monitor comprised of racetrack-ring resonators with
      defect mediated photodiodes operating in the C-band.
AB  - A CMOS compatible wavelength monitor comprised of two thermally tuned racetrack
      ring resonators with defect mediated photodiode structures is experimentally
      demonstrated in monolithic silicon. Each resonator is independently tuned so as
      to determine an unknown input wavelength by tuning the resonance peak locations
      until there is overlap between the two comb spectra. The presence of two of these
      resonator/heater components, each with a different free spectral range, increases
      the unambiguous measurement range when compared to one component used on its own.

PMID- 24104258
TI  - Generation of pseudonondiffracting optical beams with superlattice structures.
AB  - We demonstrate an approach to generate a class of pseudonondiffracting optical
      beams with the transverse shapes related to the superlattice structures. For
      constructing the superlattice waves, we consider a coherent superposition of two
      identical lattice waves with a specific relative angle in the azimuthal
      direction. We theoretically derive the general conditions of the relative angles
      for superlattice waves. In the experiment, a mask with multiple apertures which
      fulfill the conditions for superlattice structures is utilized to generate the
      pseudonondiffracting superlattice beams. With the analytical wave functions and
      experimental patterns, the pseudonondiffracting optical beams with a variety of
      structures can be generated systematically.

PMID- 24104260
TI  - Energy shedding during nonlinear self-focusing of optical beams.
AB  - Self-focusing of intense laser beams and pulses of light in real nonlinear media
      is in general accompanied by material losses that require corrections to the
      conservative Nonlinear Schrodinger equations describing their propagation. Here
      we examine loss mechanisms that exist even in lossless media and are caused by
      shedding of energy away from the self-trapping beam making it to relax to an
      exact solution of lower energy. Using the conservative NLS equations with
      absorbing boundary conditions we show that energy shedding not only occurs during
      the initial reshaping process but also during oscillatory propagation induced by
      saturation of the nonlinear effect. For pulsed input we also show that, depending
      on the sign and magnitude of dispersion, pulse splitting, energy shedding,
      collapse or stable self-focusing may result. 

PMID- 24104261
TI  - Theoretical description of bifacial optical nanomaterials.
AB  - In general, optical nanomaterials composed of noncentrosymmetric nanoscatterers
      are bifacial, meaning that two counter-propagating waves inside the material
      behave differently. Thus far a practical theory for the description of such
      materials has been missing. Herein, we present a theory that connects the design
      of the bifacial nanomaterial's "atoms" with the refractive index and wave
      impedance of the medium. We also introduce generalized Fresnel coefficients and
      investigate the role of electromagnetic multipoles on the bifaciality. We find
      that in any material two counter-propagating waves must experience the same
      refractive index, but their impedances can differ. The model is demonstrated in
      practice by the design of a nanomaterial slab with one of its facets being
      optically reflective, while the other being totally non-reflective.

PMID- 24104262
TI  - Vacuum Rabi splitting in a coupled system of single quantum dot and photonic
      crystal cavity: effect of local and propagation Green's functions.
AB  - We investigate the light emission characteristics for single two level quantum
      dot (QD) in a realistic photonic crystal (PC) L3 cavity based upon the local
      coupling strength between the QD and cavity together with the Green's function in
      which the propagation function related to the position of the detector is taken
      into account. We find for a PC cavity that the line shape of the propagation
      function in frequency domain is identical to that of the cavity and independent
      on the detector's position. We confirm that this identity is not influenced by
      the horizontal decay of the cavity. Furthermore, it is revealed that the vacuum
      fluorescence spectrum of the coupled system never give the triplet in strong
      coupling regime. Our work demonstrates that the experimental spectral-triplet in
      coupled system of single QD and PC cavity cannot be individually understood by
      vacuum Rabi splitting without including other physics mechanism. 

PMID- 24104263
TI  - Novel D-shape LSPR fiber sensor based on nano-metal strips.
AB  - In this study, a novel D-shaped localized surface plasmon resonance (LSPR) fiber
      sensor was introduced. The construction of this sensor involved etching of a
      single-mode fiber on the cladding layer and core layer, followed by plating using
      nano-metal strips. The design and calculations of the entire sensor were based on
      a numerical simulation method combining the finite element method (FEM) and the
      eigenmode expansion method (EEM). By using graphical representations of the
      algorithm results, the excitation of the LSPR was clearly observed. The finished
      D-shaped LSPR fiber sensor possesses several excellent properties, including a
      short length (2494.4301 MUm), high resolution (approximately 35 dB), and high
      sensitivity (approximately 20183.333 nm/RIU). In addition, compared with LPG-SPR
      fiber sensor, the framework provides three advantages, namely, a fabrication
      process that is compatible with semiconductor fabrication, as well as the low
      temperature cross-talk and high-temperature stability of surface grating.

PMID- 24104264
TI  - Hybrid metal-dielectric ring resonators for homogenizable optical metamaterials
      with strong magnetic response at short wavelengths down to the ultraviolet range.
AB  - We derive an analytical LC model from Maxwell's equations for the magnetic
      resonance of subwavelength ring resonators. Using the LC model, we revisit the
      scaling of split-ring resonators. Inspired by the LC model, we propose a hybrid
      metal-dielectric ring resonator mainly composed of high index dielectric material
      (e.g., TiO2) with some gaps filled with metal (e.g., Ag). The saturation
      frequency of magnetic response for the hybrid metal-dielectric ring resonator is
      much higher (up to the ultraviolet range) than that for split-ring resonators,
      and can be controlled by the metal fraction in the ring. The hybrid metal
      dielectric ring resonator can also overcome the homogenization problem of all
      dielectric magnetic resonators, and therefore can form homogenizable magnetic
      metamaterials at short wavelengths down to the ultraviolet range.

PMID- 24104265
TI  - Long time exposure digital in-line holography for 3-D particle trajectography.
AB  - One advantage of digital in-line holography is the ability for a user to know the
      3-D location of a moving particle recorded at a given time. When the time
      exposure is much larger than the time required for grabbing the particle image at
      a given location, the diffraction pattern is spread along the trajectory of this
      particle. This can be seen as a convolution between the diffraction pattern and a
      blurring function resulting from the motion of the particle during the camera
      exposure. This article shows that the reconstruction of holograms recorded under
      such conditions exhibit traces that could be processed for extracting 3D
      trajectories.

PMID- 24104266
TI  - Surface sensitivity of Rayleigh anomalies in metallic nanogratings.
AB  - Sensing schemes based on Rayleigh anomalies (RAs) in metal nanogratings exhibit
      an impressive bulk refractive-index sensitivity determined solely by the grating
      period. However, the surface sensitivity (which is a key figure of merit for
      label-free chemical and biological sensing) needs to be carefully investigated to
      assess the actual applicability of this technological platform. In this paper, we
      explore the sensitivity of RAs in metal nanogratings when local refractive-index
      changes are considered. Our studies reveal that the surface sensitivity
      deteriorates up to two orders of magnitude by comparison with the corresponding
      bulk value; interestingly, this residual sensitivity is not attributable to the
      wavelength shift of the RAs, which are completely insensitive to local refractive
      index changes, but rather to a strictly connected plasmonic effect. Our analysis
      for increasing overlay thickness reveals an ultimate surface sensitivity that
      approaches the RA bulk value, which turns out to be the upper-limit of grating
      assisted surface-plasmon-polariton sensitivities.

PMID- 24104267
TI  - High countrate real-time FCS using F2Cor.
AB  - We present a fluorescence correlation spectroscopy setup based on a software
      correlator. The setup can process autocorrelation curves in real-time at
      countrate as high as 8 MHz, with time resolution of 1 us. It uses the F2Cor
      autocorrelation algorithm, a low cost counting board and a desktop computer.
      Symmetrical normalization, which improves the signal to noise ratio of the FCS
      curve for large values of the lag-time, is adapted to the F2Cor algorithm. A new
      acquisition mode, which we call oscilloscope-mode, is presented. It takes
      advantage of the flexibility F2Cor, and proves to be very useful for optical
      setup adjustment. As an application of this setup, we performed FCS measurements
      on a reference tetramethylrhodamine solution at high concentration, up to 2.5 uM,
      which extend to the micromolar range the concentration applicable in FCS, using a
      conventional optical setup. At such high countrates the FCS curves need to be
      corrected for dead-time of the photo-detector, which was done successfully.

PMID- 24104268
TI  - A compact optical pickup head in blue wavelength with high horizontal stability
      for laser thermal lithography.
AB  - A compact optical pickup head in blue wavelength with a single-axial actuator
      i.e. focusing, for laser thermal lithography was designed, fabricated, and
      tested. The numerical aperture of the objective lens was 0.85. The linear range
      of the focus error signal was 3 MUm. A planar spring structure for improving the
      horizontal stability was designed and incorporated into the actuator. We applied
      a modified push-pull method together with a static Blu-ray re-writable disc to
      test the horizontal stability of the pickup head. We found that the in-plane
      jitter of the pickup head in two orthogonal directions were 0.34 nm and 1.59 nm,
      respectively. We demonstrated an example of applying the pickup head to write an
      inorganic photo-resist GeSbSnO film, and well-defined pattern was obtained with
      ~220 nm spot size.

PMID- 24104269
TI  - Dynamical characteristics and their applications of semiconductor lasers subject
      to both optical injection and optical feedback.
AB  - We experimentally investigate the dynamical characteristics of semiconductor
      lasers subject to both the optical injection (OI) and the optical feedback (OF).
      By coupling the OI and the OF lights into the same fiber before injecting into
      the slave laser (SL), the ratio between the two perturbations can be accurately
      determined and controlled. The frequency shifts in the cavity resonance frequency
      of the SL (nu<sub>SL</sub>) induced by the OI and the OF lights are compared
      quantitatively. To study the competition between the OI and the OF in the SL, the
      mapping of the dynamical scenarios and states are plotted in the parameter space.
      This mapping serves as the guideline for choosing the appropriate operation
      conditions in various applications employing both the OI and the OF at the same
      time. In this paper, the suitable feedback strengths to narrow the linewidths of
      photonic microwave signals generated by the OI are studied. The limitation of
      using OI in enhancing the bandwidths of the chaos states generated by the OF is
      discussed. Moreover, to suppress the unwanted dynamics due to the feedback, the
      optimal injection parameters of the OI are shown. 

PMID- 24104270
TI  - Geospatial analysis based on GIS integrated with LADAR.
AB  - In this work, we describe multi-layered analyses of a high-resolution broad-area
      LADAR data set in support of expeditionary activities. High-level features are
      extracted from the LADAR data, such as the presence and location of buildings and
      cars, and then these features are used to populate a GIS (geographic information
      system) tool. We also apply line-of-sight (LOS) analysis to develop a path
      planning module. Finally, visualization is addressed and enhanced with a gesture
      based control system that allows the user to navigate through the enhanced data
      set in a virtual immersive experience. This work has operational applications
      including military, security, disaster relief, and task-based robotic path
      planning.

PMID- 24104271
TI  - Silica microtoroid resonator sensor with monolithically integrated waveguides.
AB  - Due to their wide operating range, silica toroidal whispering gallery mode
      microresonators have enabled numerous applications from fundamental physics to
      lasing and sensing. However, the integration of a waveguide with these
      microresonators has not been achieved which limits their integration with
      additional on-chip components. Here, we demonstrate a novel approach for
      monolithically integrating a silica microtoroid with an on-chip waveguide to form
      a fully integrated microtoroid-waveguide system with quality factors in excess of
      4 million. Similar to the conventional toroidal cavities, power-independent
      operation is demonstrated. UV and temperature sensing experiments are also
      performed using the monolithically integrated microtoroid-waveguide system.

PMID- 24104272
TI  - Handedness control in a 2-MUm optical vortex parametric oscillator.
AB  - We present the first handedness control of an optical vortex output from a vortex
      pumped optical parametric oscillator. The handedness of the optical vortex was
      identical to that of the pump vortex beam. Over 2 mJ, 2-MUm optical vortex with a
      topological charge of +/- 1 was achieved. We found that the handedness of a
      fractional vortex with a half integer topological charge can also be selectively
      controlled.

PMID- 24104273
TI  - Development of a high speed laser scanning confocal microscope with an
      acquisition rate up to 200 frames per second.
AB  - There has been an increasing interest for observing fast biological phenomena
      such as cell movements in circulations and action potentials. The laser scanning
      confocal microscopy offers a good spatial resolution and optical sectioning
      ability to observe various in vivo animal models. We developed a high speed laser
      scanning confocal microscope capable of acquiring 512 by 512 pixel images at 200
      fps (frames per second). We have incorporated a fast rotating polygonal scanning
      mirror with 128 facets for the X-axis scanner. In order to increase the
      throughput of the Y-axis scanner, we applied a bi-directional scanning method for
      vertical scanning. This made it possible to scan along the Y-axis two times
      during each scanner motion cycle. For the image acquisition, we used a custom
      photomultiplier tube amplifier with a broad frequency band. In addition, custom
      imaging software was written for the new microscope. In order to verify the
      acquisition speed of the developed confocal microscope, a resolution target
      moving at a series of constant speeds and a sedated mouse with slight movements
      due to heartbeats were observed. By comparing successive frames, the frame
      acquisition speeds were calculated. 

PMID- 24104274
TI  - Tunablity of the unconventional Fano resonances in coated nanowires with radial
      anisotropy.
AB  - We establish full-wave electromagnetic scattering theory to study the near-field
      and far-field spectra of radially anisotropic coated nanowires. For coated
      nanowires containing radially anisotropic core and plasmonic shell,
      unconventional Fano resonances are predicted due to the interference between
      dipole cloaking mode and dipole resonant mode. In contrast to Z-shaped Fano
      profile with small modulation depth for coated nanospheres in Argyropoulos et al,
      Phys. Rev. Lett. 108, 263905 (2012), we predict S-shaped Fano profile with high
      depth for coated nanowires. An off-resonance field enhancement in the radially
      anisotropic core is found at the Fano dip, and its' magnitude is approximately
      the same as that the one at the low-energy resonant wavelength. Furthermore, with
      our adjustment of the inner size and the permittivity elements of the anisotropic
      core, tunable Fano-like profiles can be realized. These results may be useful for
      potential applications in different fields of nanotechnology.

PMID- 24104275
TI  - Experimental demonstration of near-infrared epsilon-near-zero multilayer
      metamaterial slabs.
AB  - Near-infrared epsilon-near-zero (ENZ) metamaterial slabs based on silver
      germanium (Ag-Ge) multilayers are experimentally demonstrated. Transmission,
      reflection and absorption spectra are characterized and used to determine the
      complex refractive indices and the effective permittivities of the ENZ
      metamaterial slabs, which match the results obtained from both the numerical
      simulations and the optical nonlocalities analysis. A rapid post-annealing
      process is used to reduce the collision frequency of silver and therefore
      decrease the optical absorption loss of multilayer metamaterial slabs.
      Furthermore, multilayer grating structures are studied to enhance the optical
      transmission and also tune the location of ENZ wavelength. The demonstrated near
      infrared ENZ multilayer metamaterial slabs are important for realizing many
      exotic applications, such as phase front shaping and engineering of photonic
      density of states.

PMID- 24104276
TI  - Finite-size limitations on Quality factor of guided resonance modes in 2D
      photonic crystals.
AB  - High-Q guided resonance modes in two-dimensional photonic crystals, enable high
      field intensity in small volumes that can be exploited to realize high
      performance sensors. We show through simulations and experiments how the Q-factor
      of guided resonance modes varies with the size of the photonic crystal, and that
      this variation is due to loss caused by scattering of in-plane propagating modes
      at the lattice boundary and coupling of incident light to fully guided modes that
      exist in the homogeneous slab outside the lattice boundary. A photonic crystal
      with reflecting boundaries, realized by Bragg mirrors with a band gap for in
      plane propagating modes, has been designed to suppress these edge effects. The
      new design represents a way around the fundamental limitation on Q-factors for
      guided resonances in finite photonic crystals. Results are presented for both
      simulated and fabricated structures. 

PMID- 24104277
TI  - Full-duplex lightwave transport systems based on long-haul SMF and optical free
      space transmissions.
AB  - A full-duplex lightwave transport system employing wavelength-division
      multiplexing (WDM) and optical add-drop multiplexing techniques, as well as
      optical free-space transmission scheme is proposed and experimentally
      demonstrated. Over an 80-km single-mode fiber (SMF) and 2.4 m optical free-space
      transmissions, impressive bit error rate (BER) performance is obtained for long
      haul fiber link and finite free-space transmission distance. Such a full-duplex
      lightwave transport system based on long-haul SMF and optical free-space
      transmissions has been successfully demonstrated, which cannot only present its
      advancement in lightwave application, but also reveal its simplicity and
      convenience for the real implementation. Our proposed systems are suitable for
      the lightwave communication systems in wired and wireless transmissions. 

PMID- 24104278
TI  - Hologram synthesis of three-dimensional real objects using portable integral
      imaging camera.
AB  - We propose a portable hologram capture system based on integral imaging. An
      integral imaging camera with an integrated micro lens array captures spatio
      angular light ray distribution of the three-dimensional scene under incoherent
      illumination. The captured light ray distribution is then processed to synthesize
      corresponding hologram. Experimental results show that the synthesized hologram
      is optically reconstructed successfully, demonstrating accommodation and motion
      parallax of the reconstructed three-dimensional scene. 

PMID- 24104279
TI  - X-ray phase tomography of a moving object.
AB  - We propose an algorithm for tomographic reconstruction of the refractive index
      map of an object translated across a fan-shaped X-ray beam. We adopt a forward
      image model valid under the non-paraxial condition, and use a unique mapping of
      the acquired projection images to reduce the computational cost. Even though the
      imaging setup affords only a limited angular coverage, our algorithm provides
      accurate refractive index values by employing the positivity and piecewise
      smoothness constraints. 

PMID- 24104280
TI  - Novel method for converting digital Fresnel hologram to phase-only hologram based
      on bidirectional error diffusion.
AB  - We report a novel and fast method for converting a digital, complex Fresnel
      hologram into a phase-only hologram. Briefly, the pixels in the complex hologram
      are scanned sequentially in a row by row manner. The odd and even rows are
      scanned from opposite directions, constituting to a bidirectional error diffusion
      process. The magnitude of each visited pixel is forced to be a constant value,
      while preserving the exact phase value. The resulting error is diffused to the
      neighboring pixels that have not been visited before. The resulting novel phase
      only hologram is called the bidirectional error diffusion (BERD) hologram. The
      reconstructed image from the BERD hologram exhibits high fidelity as compared
      with those obtained with the original complex hologram. 

PMID- 24104281
TI  - Analytical theory for the nonlinear optical response of a Kerr-type standing-wave
      cavity side-coupling to a MIM waveguide.
AB  - In this article, an analytical theory to describe the nonlinear dynamic response
      characteristics of a typical SPP waveguide-cavity structure formed by a Kerr-type
      standing-wave cavity side-coupling to a metal-insulator-metal (MIM) waveguide is
      proposed by combining the temporal coupled mode theory and the Kerr nonlinearity.
      With the analytical theory, the optical bistability with the hysteresis behavior
      is successfully predicted, and the optical bistability evolutions and its dynamic
      physical mechanism are also phenomenologically analyzed. Moreover, the influence
      of the quality factors Q0 and Q1 on the first-turnning point (FTP) power of
      optical bistability and the bistable region width, the approaches to decrease the
      FTP power and to broaden the bistable region are also discussed in detail with
      our analytical theory. This work can help us understand the physical mechanism of
      the nonlinear dynamical response at nanoscale, and may be useful to design
      nonlinear nanophotonic systems for applications in ultra-compact all-optical
      devices and storages.

PMID- 24104282
TI  - Bias-dependent distortion in optical comb-based analog optical links.
AB  - We provide the first experimental demonstration of the impact of bias-frequency
      on second-order distortion in sampled analog optical links. We show proper
      selection of bias frequency yields >48 dB improvement in second-order distortion
      performance. In addition, we demonstrate that measurement of the average
      frequency of the optical comb may be used to determine the optimum bias frequency
      - without the need for involved radio-frequency distortion measurements. 

PMID- 24104283
TI  - Novel vortex-transform for high frequency modulated patterns.
AB  - A novel vortex-transform is proposed. This transform allows for generating
      complex-valued functions from modulated intensity patterns, including high
      frequency components from modulation, without the generation of unstable phase
      singularities. From these complex-valued functions it is possible to obtain
      intensity and pseudo-phase maps to analyze the intensity recordings without the
      necessity of phase retrieval techniques. The intensity and pseudo-phase maps
      obtained by using this transform preserve the modulation structure onto the
      intensity and phase modulo 2pi maps, including stable phase singularities.

PMID- 24104284
TI  - Giant omnidirectional radiation enhancement via radially anisotropic zero-index
      metamaterial.
AB  - We demonstrate a remarkable enhancement of isotropic radiation via radially
      anisotropic zero-index metamaterial (RAZIM). The radiation power can be enhanced
      by an order of magnitude when a line source and a dielectric particle is enclosed
      by a RAZIM shell. Based on the extended Mie theory, we illustrate that the basic
      physics of this isotropic radiation enhancement lies in the confinement of higher
      order anisotropic modes by the RAZIM shell. The confinement results in some high
      field regions within the RAZIM shell and thus enables strong scattering from the
      dielectric particle therein, giving rise to a giant amplification of isotropic
      radiation out of the system. The influence of the loss inherent in the RAZIM
      shell is also examined. It is found that the attenuation of omnidirectional power
      enhancement due to the loss in the RAZIM can be compensated by gain particles.

PMID- 24104285
TI  - First harmonic with wavelength modulation spectroscopy to measure integrated
      absorbance under low absorption.
AB  - Integrated absorbance (IA) can be used to infer gas temperature and concentration
      directly, in this paper, we proposed a new method that uses the 1st harmonic to
      measure the IA under low absorption conditions (<10%). Subsequently, a large
      number of numerical simulations are used to validate the reliability and accuracy
      of this method, and several absorption lines of CO2 and H2O molecules near 6981
      cm-1 are selected to determine the IA and species concentration in experiments.
      Calculation and experiment results show that the proposed method can accurately
      measure IA in actual measurements.

PMID- 24104286
TI  - Terahertz wireless communications based on photonics technologies.
AB  - There has been an increasing interest in the application of terahertz (THz) waves
      to broadband wireless communications. In particular, use of frequencies above 275
      GHz is one of the strong concerns among radio scientists and engineers, because
      these frequency bands have not yet been allocated at specific active services,
      and there is a possibility to employ extremely large bandwidths for ultra
      broadband wireless communications. Introduction of photonics technologies for
      signal generation, modulation and detection is effective not only to enhance the
      bandwidth and/or the data rate, but also to combine fiber-optic (wired) and
      wireless networks. This paper reviews recent progress in THz wireless
      communications using telecom-based photonics technologies towards 100 Gbit/s. 

PMID- 24104287
TI  - Terahertz wave transmission in flexible polystyrene-lined hollow metallic
      waveguides for the 2.5-5 THz band.
AB  - A low-loss and low-dispersive optical-fiber-like hybrid HE11 mode is developed
      within a wide band in metallic hollow waveguides if their inner walls are coated
      with a thin dielectric layer. We investigate terahertz (THz) transmission losses
      from 0.5 to 5.5 THz and bending losses at 2.85 THz in a polystyrene-lined silver
      waveguides with core diameters small enough (1 mm) to minimize the number of
      undesired modes and to make the waveguide flexible, while keeping the
      transmission loss of the HE11 mode low. The experimentally measured loss is below
      10 dB/m for 2 < nu < 2.85 THz (~4-4.5 dB/m at 2.85 THz) and it is estimated to be
      below 3 dB/m for 3 < nu < 5 THz according to the numerical calculations. At ~1.25
      THz, the waveguide shows an absorption peak of ~75 dB/m related to the transition
      between the TM11-like mode and the HE11 mode. Numerical modeling reproduces the
      measured absorption spectrum but underestimates the losses at the absorption
      peak, suggesting imperfections in the waveguide walls and that the losses can be
      reduced further.

PMID- 24104288
TI  - Physical layer secret key generation for fiber-optical networks.
AB  - We propose and experimentally demonstrate a method for generating and sharing a
      secret key using phase fluctuations in fiber optical links. The obtained key can
      be readily used to support secure communication between the parties. The security
      of our approach is based on a fundamental asymmetry associated with the optical
      physical layer: the sophistication of tools needed by an eavesdropping adversary
      to subvert the key establishment is significantly greater and more costly than
      the complexity needed by the legitimate parties to implement the scheme. In this
      sense, the method is similar to the classical asymmetric algorithms (Diffie
      Hellman, RSA, etc.).

PMID- 24104289
TI  - Femtosecond-laser-induced shockwaves in water generated at an air-water
      interface.
AB  - We report generation of femtosecond-laser-induced shockwaves at an air-water
      interface by millijoule femtosecond laser pulses. We document and discuss the
      main processes accompanying this phenomenon, including light emission,
      development of the ablation plume in the air, formation of an ablation cavity,
      and, subsequently, a bubble developing in water. We also discuss the possibility
      of remotely controlling the characteristics of laser-induced sound waves in water
      through linear acoustic superposition of sound waves that results from millijoule
      femtosecond laser-pulse interaction with an air-water interface, thus opening up
      the possibility of remote acoustic applications in oceanic and riverine
      environments. 

PMID- 24104290
TI  - Shockwave based nonlinear optical manipulation in densely scattering opaque
      suspensions.
AB  - Optical manipulation of particulate-loaded, highly scattering (opaque)
      suspensions is considered impossible. Here we demonstrate theoretically and
      experimentally optical manipulation of the local properties of such opaque
      suspensions. We show that the optical forces exerted by multiply-scattered light
      give rise to dense shock fronts of particle concentration, propagating deep
      inside the opaque suspensions, where the optical field is completely diffuse. We
      exploit these waves to demonstrate a plethora of optofluidic manipulations,
      ranging from optical transport and concentration of large populations of
      nanoparticles, to light-induced 'writing' of concentrated spots in the
      suspensions and light-induced phase-transition from suspension to gel in
      localized volumes inside the fluids. 

PMID- 24104291
TI  - A novel structure for tunable terahertz absorber based on graphene.
AB  - Graphene can be used as a platform for tunable absorbers for its tunability of
      conductivity. In this paper, we proposed an "uneven dielectric slab structure"
      for the terahertz (THz) tunable absorber based on graphene. The absorber consists
      of graphene-dielectric stacks and an electric conductor layer, which is easy to
      fabricate in the manufacturing technique. Fine tuning of the absorption
      resonances can be conveniently achieved by adjusting the bias voltage. Both
      narrowband and broadband tunable absorbers made of this structure are
      demonstrated without using a patterned graphene. In addition, this type of
      graphene-based absorber exhibits stable resonances with a wide range angles of
      obliquely incident electromagnetic waves. 

PMID- 24104292
TI  - Ambient refractive index-independent bending vector sensor based on seven-core
      photonic crystal fiber using lateral offset splicing.
AB  - A novel, simple, and compact optical fiber directional bending vector sensor
      based on Mach-Zehnder interferometer (MZI) is proposed and experimentally
      demonstrated. The device consists of a piece of seven-core photonic crystal fiber
      (PCF) sandwiched between two single mode fibers (SMFs) with a lateral offset
      splicing joint that covering two cores of PCF. Bending sensitivity of the seven
      core PCF based MZI is changed by an axial rotation angle, which shows its
      capacity for recognizing positive and negative directions. Within a curvature
      range of -7.05 m-1 to 7.05 m-1, the calculated bending sensitivities of two
      resonant central wavelengths with opposite fiber orientations are 1.232 nm/m-1
      and 1.174 nm/m-1, respectively. This novel MZI is formed by invoking interference
      between the LP01-like supermode and other higher order supermodes in the core,
      which leads to insensitive to ambient refractive index (ARI). We have also
      investigated the transmission characteristics of the sensor with the temperature
      change.

PMID- 24104293
TI  - Photon counting compressive depth mapping.
AB  - We demonstrate a compressed sensing, photon counting lidar system based on the
      single-pixel camera. Our technique recovers both depth and intensity maps from a
      single under-sampled set of incoherent, linear projections of a scene of interest
      at ultra-low light levels around 0.5 picowatts. Only two-dimensional
      reconstructions are required to image a three-dimensional scene. We demonstrate
      intensity imaging and depth mapping at 256 * 256 pixel transverse resolution with
      acquisition times as short as 3 seconds. We also show novelty filtering,
      reconstructing only the difference between two instances of a scene. Finally, we
      acquire 32 * 32 pixel real-time video for three-dimensional object tracking at 14
      frames-per-second. 

PMID- 24104294
TI  - Low-loss hybrid fiber with zero dispersion wavelength shifted to 1 um.
AB  - We proposed and investigated a novel type of all-glass hybrid fiber where light
      is confined in the low-index core due to both total internal reflection and
      coherent Fresnel reflection (a photonic bandgap mechanism). The hybrid mode has
      an anomalous dispersion of 13 ps/(nm km) at 1064 nm and low loss (~6 dB/km), and
      it can be easily excited by splicing with a single-mode step-index fiber. The
      compression of positively chirped 8 ps pulses down to 330 fs was demonstrated
      with the fabricated hybrid fiber. 

PMID- 24104295
TI  - 2-um Tm:Lu2O3 ceramic disk laser intracavity-pumped by a semiconductor disk
      laser.
AB  - A proof-of-principle study of a 1.97-um Tm:Lu<sub>2</sub>O<sub>3</sub> ceramic
      disk laser, intracavity pumped by a 1.2-um semiconductor disk laser, is
      presented. The demonstrated concept allows for improved pump absorption and takes
      advantage of the broad wavelength coverage provided by semiconductor disk laser
      technology. For thin disk lasers the small thickness of the gain element
      typically leads to inefficient pump light absorption. This problem is usually
      solved by using a complex multi-pass pump arrangement. In this study we address
      this challenge with a new laser concept of an intracavity pumped ceramic thin
      disk laser. The output power at 1.97 um was limited to 250 mW due to heat
      spreader-less mounting scheme of the ceramic gain disk. 

PMID- 24104296
TI  - Study of heating capacity of focused IR light soldering systems.
AB  - An experimental study about four optical setups used for developing a Focused IR
      Light Soldering System (FILSS) for Surface Mount Technology (SMT) lead-free
      electronic devices specifically for Ball Grid Arrays (BGA) is presented. An
      analysis of irradiance and infrared thermography at BGA surface is presented, as
      well as heat transfer by radiation and conduction process from the surface of the
      BGA to the solder balls. The results of this work show that the heating provided
      by our proposed optical setups, measured at the BGA under soldering process,
      meets the high temperature and uniform thermal distribution requirements, which
      are defined by the reflow solder method for SMT devices. 

PMID- 24104297
TI  - Experimental observation of vector solitons in a highly birefringent cavity of
      ytterbium-doped fiber laser.
AB  - We report on the first experimental observation of dark-bright and dark-dark
      vector solitons in a highly birefringent cavity of all-normal-dispersion
      ytterbium-doped fiber laser. With the usage of different length of polarization
      maintaining fibers in the cavity, totally four types of vector solitons with
      different features were observed.

PMID- 24104298
TI  - All-optical hash code generation and verification for low latency communications.
AB  - We introduce an all-optical, format transparent hash code generator and a hash
      comparator for data packets verification with low latency at high baudrate. The
      device is reconfigurable and able to generate hash codes based on arbitrary
      functions and perform the comparison directly in the optical domain. Hash codes
      are calculated with custom interferometric circuits implemented with a Fourier
      domain optical processor. A novel nonlinear scheme featuring multiple four-wave
      mixing processes in a single waveguide is implemented for simultaneous phase and
      amplitude comparison of the hash codes before and after transmission. We
      demonstrate the technique with single polarisation BPSK and QPSK signals up to a
      data rate of 80 Gb/s.

PMID- 24104299
TI  - A Zernike mode decomposition decoupling control algorithm for dual deformable
      mirrors adaptive optics system.
AB  - A simple but effective decoupling control algorithm based on Zernike mode
      decomposition for adaptive optics systems with dual deformable mirrors is
      proposed. One of the two deformable mirrors is characterized with a large stroke
      (woofer) and the other with high spatial resolutions (tweeter). The algorithm
      works as follows: wavefront gradient vector is decoupled using the Zernike modes
      at first, and then the control vector for the woofer is generated with low order
      Zernike coefficients to eliminate high order modes. At the same time the control
      vector for the tweeter is reset by a constraint matrix in order to avoid coupling
      error accumulation. Simulation indicates the algorithm could get better
      performance compared with traditional Zernike mode decomposition control
      algorithms. Experiments demonstrate that this algorithm can effectively
      compensate for phase distortions and significantly suppress the coupling between
      the woofer and tweeter.

PMID- 24104300
TI  - Simple full-range carrier frequency offset estimation for high speed CO-OFDM.
AB  - We propose a simple, full-range carrier frequency offset (CFO) algorithm for
      coherent optical orthogonal frequency division multiplexing (CO-OFDM) systems. By
      applying the Chinese remainder theorem (CRT) to training symbol of single
      frequency, the proposed CFO algorithm has wide range with shorter training
      symbol. We numerically and experimentally demonstrate the performance of CRT
      based algorithms in a 16-ary quadrature amplitude modulation (QAM) CO-OFDM
      system. The results show that the estimation range of the CRT-based algorithm is
      full-range corresponding to the sampling frequency. Also, the bit error ratio
      (BER) degradation of the proposed algorithm with one training symbol is
      negligible. These results indicate that the proposed algorithm can be used as a
      wide range CFO estimator with an increased data rate in high speed CO-OFDM
      systems. 

PMID- 24104301
TI  - Low-loss light transport at the subwavelength scale in silicon nano-slot based
      symmetric hybrid plasmonic waveguiding schemes.
AB  - A hybrid plasmonic structure comprising a silicon slot waveguide separated from
      an inverse metal ridge by a thin low-index insulator gap is proposed and
      investigated. Owing to its symmetric hybrid configuration containing closely
      spaced silicon rails near the metal ridge, the fundamental symmetric hybrid slot
      mode supported by the structure is demonstrated to be capable of simultaneously
      achieving low propagation loss and subwavelength field confinement within a wide
      range of physical dimensions at the telecom wavelength. Comprehensive numerical
      investigations regarding the effects of key geometric parameters on the guided
      modes' properties, including the slot sizes, the shape and dimension of the
      silicon rails, the width of the gap region as well as the height of metallic
      nanoridge, have been conducted. It is revealed that the propagation distance of
      the symmetric mode can be more than several millimeters (even up to the
      centimeter range), while simultaneously achieving a subwavelength mode size and
      tight field confinement inside the gap region. In addition to the studies on the
      modal characteristics, excitation strategies of the guided hybrid modes and the
      conversion between dielectric slot and hybrid slot modes are also numerically
      demonstrated. The studied platform potentially combines the advantages of silicon
      slot and plasmonic structures, which might lay important groundwork for future
      hybrid integrated photonic components and circuits.

PMID- 24104302
TI  - A fast fluorescence imaging flow cytometer for phytoplankton analysis.
AB  - We report a fast fluorescence imaging flow cytometer for phytoplankton analysis
      that can achieve a volume flow rate up to 1ml/min. The instrument shows a high
      immunity to motion blur in image captured with a lateral resolution of 0.75 +/-
      0.06 MUm for a wide size range ~1 MUm to ~200 MUm. This is made possible by
      suppressing the out-of-focus light using thin light sheet illumination and image
      deconvolution, and by precluding the motion-blur with a unique flow
      configuration. Preliminary results from untreated coastal water samples show the
      technique has high potential as a practical field instrument for monitoring
      phytoplankton abundance and species composition.

PMID- 24104303
TI  - Lower operation voltage in dual-frequency cholesteric liquid crystals based on
      the thermodielectric effect.
AB  - Dual-frequency cholesteric liquid crystal (DFCLC) devices characteristically
      require high operation voltage, which hinders their further development in thin
      film-transistor driving. Here we report on a lower-voltage switching method based
      on the thermodielectric effect. This technique entails applying a high-frequency
      voltage to occasion dielectric oscillation heating so to induce the increase in
      crossover frequency. The subsequent change in dielectric anisotropy of the DFCLC
      allows the switching, with a lower operation voltage, from the planar state to
      the focal conic or homeotropic state. The temperature rise incurred by the
      dielectric heating is described.

PMID- 24104304
TI  - Dynamic focus-tracking MEMS scanning micromirror with low actuation voltages for
      endoscopic imaging.
AB  - We demonstrate a 3-D scanning micromirror device that combines 2-D beam scanning
      with focus control in the same device using micro-electro-mechanical-systems
      (MEMS) technology. 2-D beam scanning is achieved with a biaxial gimbal structure
      and focus control is obtained with a deformable mirror membrane surface. The
      micromirror with 800 micrometer diameter is designed to be sufficiently compact
      and efficient so that it can be incorporated into an endoscopic imaging probe in
      the future. The design, fabrication and characterization of the device are
      described in this paper. Using the focus-tracking MEMS scanning mirror, we
      achieved an optical scanning range of >16 degrees with <40 V actuation voltage at
      resonance and a tunable focal length between infinity and 25 mm with <100V
      applied bias. 

PMID- 24104305
TI  - Experimental characterization of an uniaxial angle cut whispering gallery mode
      resonator.
AB  - The usual configuration of uniaxial whispering gallery mode resonators is a disk
      shaped geometry where the optic axis points along the symmetry axis, a so called
      z-cut resonator. Recently x-cut resonators, where the optic axis lies in the
      equatorial plane, became of interest as they enable extremely broadband second
      harmonic generation. In this paper we report on the properties of a more
      generalized system, the so called angle-cut resonator, where the optic axis
      exhibits an arbitrary angle against the symmetry axis. We show experimentally
      that the modal structure and quality factors are similar to common resonators but
      that the polarization properties differ quite significantly: due to the asymmetry
      the polarization depends on the equatorial position and is, in general,
      elliptical. 

PMID- 24104306
TI  - Generation of ultra-narrow, stable and tunable millimeter- and terahertz- waves
      with very low phase noise.
AB  - The interference between two spectral lines of the frequency comb of a fiber
      femtosecond laser is used to generate millimeter-wave and terahertz tones. The
      two lines are selected by stimulated Brillouin scattering (SBS) amplification.
      All other modes are strongly rejected based on polarization discrimination, using
      the polarization-pulling effect that is associated with SBS. The inherent high
      spectral quality of a femtosecond fiber laser comb allows generation of
      millimeter- and terahertz waves with linewidths below 1 Hz, and a phase noise of 
      105 dBc/Hz at 10 kHz offset. The generation, free-space transmission and
      detection of continuous waves at 1 THz are demonstrated as well. Lastly, the
      generated millimeter-wave carriers are modulated by 40 Gbit/s data. The entire
      system consists of a fiber laser and standard equipment of optical
      telecommunications. Besides metrology, spectroscopy and astronomy, the method can
      be utilized for the emergent field of wireless millimeter-wave and THz
      communications at ultra-high data rates.

PMID- 24104307
TI  - Three-beam interference with circular polarization for structured illumination
      microscopy.
AB  - Three-dimensional structured illumination microscopy (3D-SIM) is a wide-field
      technique that can provide doubled resolution and improved image contrast. In
      this work, we demonstrate a simple approach to 3D-SIM - using three-beam
      interference with circular polarization to generate the pattern of structured
      illumination, so that the modulation contrast is routinely maintained at all
      orientations without a complicated polarization rotator or mechanical motion. We
      derive the resultant intensity distribution of the interference pattern to
      confirm the modulation contrast independent of orientation, and compare the
      result with those using interfering beams of linear polarization. To evaluate the
      influence of the modulation contrast on imaging, we compare the simulated SIM
      images of 100-nm beads. Experimental results are presented to confirm the
      simulations. Our approach requires merely a lambda/4-wave plate to alter the
      interfering beams from linear to circular polarization. This simplicity together
      with the use of a spatial light modulator to control the interference pattern
      facilitates the implementation of a 3D-SIM system and should broaden its
      application. 

PMID- 24104308
TI  - Fiber fault location utilizing traffic signal in optical network.
AB  - We propose and experimentally demonstrate a method for fault location in optical
      communication network. This method utilizes the traffic signal transmitted across
      the network as probe signal, and then locates the fault by correlation technique.
      Compared with conventional techniques, our method has a simple structure and low
      operation expenditure, because no additional device is used, such as light
      source, modulator and signal generator. The correlation detection in this method
      overcomes the tradeoff between spatial resolution and measurement range in pulse
      ranging technique. Moreover, signal extraction process can improve the location
      result considerably. Experimental results show that we achieve a spatial
      resolution of 8 cm and detection range of over 23 km with -8-dBm mean launched
      power in optical network based on synchronous digital hierarchy protocols. 

PMID- 24104309
TI  - Imaging through scattering microfluidic channels by digital holography for
      information recovery in lab on chip.
AB  - We tackle the problem of information recovery and imaging through scattering
      microfluidic chips by means of digital holography (DH). In many cases the chip
      can become opalescent due to residual deposits settling down the inner channel
      faces, biofilm formation, scattering particle uptake by the channel cladding or
      its damaging by corrosive substances, or even by condensing effect on the
      exterior channels walls. In these cases white-light imaging is severely degraded
      and no information is obtainable at all about the flowing samples. Here we
      investigate the problem of counting and estimating velocity of cells flowing
      inside a scattering chip. Moreover we propose and test a method based on the
      recording of multiple digital holograms to retrieve improved phase-contrast
      images despite the strong scattering effect. This method helps, thanks to DH, to
      recover information which, otherwise, would be completely lost.

PMID- 24104310
TI  - What percentage of the oceanic mixed layer is accessible to marine Lidar? Global
      and the Gulf of Mexico prospective.
AB  - The oceanic mixed layer is a nearly homogenous region of the upper ocean which,
      in principle, has a little or no variation in turbulence strength, temperature or
      density with depth. This layer mediates oceanic fluxes of gas, momentum and heat.
      Here, based on the chosen marine Lidar system, we have carried out estimates of
      the depth penetration of the Lidar when compared to the local mixed layer depth.
      On average, we have found that at least 50% of the global oceanic mixed layer
      depth is accessible to the Lidar observations. When operating in a single
      scattering mode, which is more attenuating but more amenable to analysis, the
      modeled Lidar was found to access 0.4 of global mixed layer depth in half of the
      cases. The single scattering Lidar was found to access a large fraction of the
      equatorial mixed layer - a region very important when addressing global climatic
      issues. In a coastal environment such as the Gulf of Mexico the single scattering
      Lidar was found to penetrate upper half of the mixed layer, underscoring the
      potential for Lidar to address environmental issues there.

PMID- 24104311
TI  - Sparsity-based super-resolution and phase-retrieval in waveguide arrays.
AB  - We present a scheme for recovering the complex input field launched into a
      waveguide array, from partial measurements of its output intensity, given advance
      knowledge that the input is sparse. In spite of the fact that in general the
      inversion problem is ill-conditioned, we demonstrate experimentally and in
      simulations that the prior knowledge of sparsity helps overcome the loss of
      information. Our method is based on GESPAR, a recently proposed efficient phase
      retrieval algorithm. Possible applications include optical interconnects and
      quantum state tomography, and the ideas are extendable to other multiple input
      and multiple output (MIMO) communication schemes. 

PMID- 24104312
TI  - Assessment of the flow velocity of blood cells in a microfluidic device using
      joint spectral and time domain optical coherence tomography.
AB  - Although Doppler optical coherence tomography techniques have enabled the imaging
      of blood flow in mid-sized vessels in biological tissues, the generation of
      velocity maps of capillary networks remains a challenge. To better understand the
      origin and information content of the Doppler signal from small vessels and
      limitations of such measurements, we used joint spectral and time domain optical
      coherence tomography to monitor the flow in a model, semitransparent microchannel
      device. The results obtained for Intralipid, whole blood, as well as separated
      red blood cells indicate that the technique is suitable to record velocity
      profiles in vitro, in a range of microchannel configurations. 

PMID- 24104313
TI  - Impact of fiber outer boundaries on leaky mode losses in leakage channel fibers.
AB  - In a leakage channel fiber, the desired fundamental mode (FM) has negligible
      waveguide loss. Higher-order modes (HOM) are designed to have much higher
      waveguide losses so that they are practically eliminated during propagation.
      Coherent reflection at the fiber outer boundary can lead to additional
      confinement especially for highly leaky HOM, leading to lower HOM losses than
      what are predicted by conventional FEM mode solver considering infinite cladding.
      In this work, we conducted, for the first time, careful measurements of HOM
      losses in two leakage channel fibers (LCF) with circular and rounded hexagonal
      boundary shapes respectively. Impact on HOM losses from coiling, fiber boundary
      shapes and coating indexes were studied in comparison to simulations. This work,
      for the first time, demonstrates the limit of the simulation method commonly used
      in the large-mode-area fiber designs and the need for an improved approach. More
      importantly, this work also demonstrates that a deviation from circular fiber
      outer shape may be an effective method to mitigate HOM loss reduction from
      coherent reflection from fiber outer boundary, even in double-clad fibers, with
      HOM losses in excess of 20 dB/m measured in the hexagonal LCF with ~50 um core
      diameter while keeping FM loss negligible.

PMID- 24104314
TI  - Absorption mechanism of the second pulse in double-pulse femtosecond laser glass
      microwelding.
AB  - The absorption mechanism of the second pulse is experimentally and theoretically
      investigated for high-efficiency microwelding of photosensitive glass by double
      pulse irradiation using a femtosecond laser. The transient absorption change
      during the second pulse irradiation for various energies induced by the first
      pulse is measured at different delay times. The resulting effects depend on
      whether the delay time is 0-30 ps (time domain I) or 30- several ns (domain II).
      By solving rate equations for the proposed electronic processes, the excitation
      and relaxation times of free electrons in time domain I are estimated to be 0.98
      and 20.4 ps, respectively, whereas the relaxation times from the conduction band
      to a localized state and from the localized state to the valence band in domain
      II are 104.2 and 714.3 ps, respectively. Single-photon absorption of the second
      pulse by free electrons dominates in domain I, resulting in high bonding
      strength. In time domain II, about 46% of the second pulse is absorbed by a
      single photon due to the localized state, which is responsible for higher bonding
      strength compared with that prepared by single-pulse irradiation.

PMID- 24104315
TI  - High-speed transport-of-intensity phase microscopy with an electrically tunable
      lens.
AB  - We present a high-speed transport-of-intensity equation (TIE) quantitative phase
      microscopy technique, named TL-TIE, by combining an electrically tunable lens
      with a conventional transmission microscope. This permits the specimen at
      different focus position to be imaged in rapid succession, with constant
      magnification and no physically moving parts. The simplified image stack
      collection significantly reduces the acquisition time, allows for the diffraction
      limited through-focus intensity stack collection at 15 frames per second, making
      dynamic TIE phase imaging possible. The technique is demonstrated by profiling of
      microlens array using optimal frequency selection scheme, and time-lapse imaging
      of live breast cancer cells by inversion the defocused phase optical transfer
      function to correct the phase blurring in traditional TIE. Experimental results
      illustrate its outstanding capability of the technique for quantitative phase
      imaging, through a simple, non-interferometric, high-speed, high-resolution, and
      unwrapping-free approach with prosperous applications in micro-optics, life
      sciences and bio-photonics.

PMID- 24104316
TI  - Temperature-compensated fiber-optic 3D shape sensor based on femtosecond laser
      direct-written Bragg grating waveguides.
AB  - Temperature-compensated 3D fiber shape sensing is demonstrated with femtosecond
      laser direct-written optical and Bragg grating waveguides that were distributed
      axially and radially inside a single coreless optical fiber. Efficient light
      coupling between the laser-written optical circuit elements and a standard single
      mode fiber (SMF) was obtained for the first time by 3D laser writing of a 1 * 3
      directional coupler to meet with the core waveguide in the fusion-spliced SMF.
      Simultaneous interrogation of nine Bragg gratings, distributed along three
      laterally offset waveguides, is presented through a single waveguide port at 1
      kHz sampling rate to follow the Bragg wavelength shifts in real-time and thereby
      infer shape and temperature profile unambiguously along the fiber length. This
      distributed 3D strain and thermal sensor is freestanding, flexible, compact,
      lightweight and opens new directions for creating fiber cladding photonic devices
      for a wide range of applications from shape and thermal sensing to guidance of
      biomedical catheters and tools in minimally invasive surgery. 

PMID- 24104317
TI  - Folded cavity angled-grating broad-area lasers.
AB  - The angled-grating broad-area laser is a promising candidate for high power, high
      brightness diode laser source. The key point in the design is the angled gratings
      which can simultaneously support the unique snake-like zigzag lasing mode and
      eliminate the direct Fabry-Perot (FP) feedback. Unlike a conventional laser
      waveguide mode, the phase front of the zigzag mode periodically changes along the
      propagation direction. By use of the mirror symmetry of the zigzag mode, we
      propose and demonstrate the folded cavity angled-grating broad-area lasers. One
      benefit of this design is to reduce the required wafer space compared to a
      regular angled-grating broad-area laser, especially in a long cavity laser for
      high power operation. Experimental results show that the folded cavity laser
      exhibits good beam quality in far field with a slightly larger threshold and
      smaller slope efficiency due to the additional interface loss. 

PMID- 24104318
TI  - Coherent-form energy conservation relation for the elastic scattering of a guided
      mode in a symmetric scattering system.
AB  - We propose a coherent-form energy conservation relation (ECR) that is generally
      valid for the elastic transmission and reflection of a guided mode in a symmetric
      scattering system. In contrast with the classical incoherent-form ECR, |tau|2 +
      |rho|2<=1 with tau and rho denoting the elastic transmission and reflection
      coefficients of a guided mode, the coherent-form ECR is expressed as |tau +
      rho|<=1, which imposes a constraint on a coherent superposition of the
      transmitted and reflected modes. The coherent-form ECR is rigorously demonstrated
      and is numerically tested by considering different types of modes in various
      scattering systems. Further discussions with the scattering matrix formalism
      indicate that two coherent-form ECRs, |tau + rho|<=1 and |tau-rho|<=1, along with
      the classical ECR |tau|2 + |rho|2<=1 constitute a complete description of the
      energy conservation for the elastic scattering of a guided mode in a symmetric
      scattering system. The coherent-form ECR provides a common tool in terms of
      energy transfer for understanding and analyzing the scattering dynamics in
      currently interested scattering systems.

PMID- 24104319
TI  - Simulating the spatial luminance distribution of planar light sources by sampling
      of ray files.
AB  - Ray files offer a very accurate description of the optical characteristics of a
      light source. This is essential whenever optical components are positioned in
      close proximity (near-field) of the light source in order to perform accurate ray
      tracing simulations. However, a ray file does not allow for a direct simulation
      of the spatial luminance distribution, i.e. luminance map, by off-the-shelf ray
      tracers. Simulating luminance maps of light sources or luminaires is especially
      important in general lighting in order to predict their general perception when
      viewed by the observer, and more specific, the perception of glare of luminaires
      having a non-uniform luminance distribution. To enable the simulation of
      luminance maps while maintaining the high accuracy offered by a ray file, a
      sampling method is presented. To validate the approach, near-field
      goniophotometer measurements of two planar light sources were performed. From
      these measurement data, ray files were extracted to which the sampling method was
      applied in order to obtain a set of surface sources. This approach was validated
      by comparing measured luminance images with simulated luminance images. A good
      agreement was found, validating the presented method. 

PMID- 24104320
TI  - Righting the handedness' dichotomy: schemes of Sagnac interferometer containing
      chiral elements for suppression of dependence on circular birefringence and
      circular dichroism.
AB  - We present two configurations (one with and another without a half-wave plate) of
      a Sagnac interferometer (SI) containing chiral optical elements where either the
      Sagnac loop mirror's (SLM) reflectance is circular birefringence (CB) independent
      or polarization dependence/circular dichroism (CD) is canceled in both reflection
      and transmission. These schemes allow use of chiral components as feedback
      elements/filters in SLM of a laser and in switches/modulators and sensors
      requiring compensation of chiral media CD, as well as allowing calibration of CD
      measurements. We also compare/show the differences between SI containing devices
      with either CB or linear birefringence (LB). 

PMID- 24104322
TI  - Observation of CEP effect via filamentation in transparent solids.
AB  - We report on the first direct observation of carrier-envelope-phase (CEP) effect
      during the interaction between few-cycle laser pulses and bulk solid materials.
      Using 2-cycle mid-infrared laser pulses with stabilized CEP, the CEP effect of
      tunneling ionization during the laser filamentation in a fused silica is
      revealed. The phase variation of the accompanying supercontinuum (SC) emission
      with filamentation at different CEPs of laser pulses can be measured by means of
      spectral interference technique, as a direct manifestation of the strong field
      tunneling ionization dynamics in transparent solids. 

PMID- 24104324
TI  - Large-area electromagnetic enhancement by a resonant excitation of surface waves
      on a metallic surface with periodic subwavelength patterns.
AB  - We theoretically investigate the electromagnetic enhancement on a metallic
      surface patterned with periodic subwavelength structures. Fully-vectorial
      calculations show a large-area electromagnetic enhancement (LAEE) on the surface,
      which strongly contrasts with the previously reported "hot spots" that occur in
      specific tiny regions and which relieves the rigorous requirement of the nano
      scale location of sample molecules. The LAEE allows for designing more
      practicable substrates for many enhanced-spectra applications. By building up
      microscopic models, the LAEE is shown due to a resonant excitation of surface
      waves that include both the surface plasmon polariton (SPP) and a quasi
      cylindrical wave (QCW). The surface waves propagate on the substrate over a long
      distance and thus greatly enlarge the area of electromagnetic enhancement
      compared to the nano-sized hot spots caused by localized modes. Gain medium is
      introduced to further strengthen the large-area surface-wave resonance, with
      which an enhancement factor (EF) of electric-field intensity up to a few
      thousands is achieved.

PMID- 24104323
TI  - Far-red fluorescence gene reporter tomography for determination of placement and
      viability of cell-based gene therapies.
AB  - Non-invasive injectable cellular therapeutic strategies based on sustained
      delivery of physiological levels of BMP-2 for spinal fusion are emerging as
      promising alternatives, which could provide sufficient fusion without the
      associated surgical risks. However, these injectable therapies are dependent on
      bone formation occurring only at the specific target region. In this study, we
      developed and deployed fluorescence gene reporter tomography (FGRT) to provide
      information on in vivo cell localization and viability. This information is
      sought to confirm the ideal placement of the materials with respect to the area
      where early bone reaction is required, ultimately providing three dimensional
      data about the future fusion. However, because almost all conventional
      fluorescence gene reporters require visible excitation wavelengths, current in
      vivo imaging of fluorescent proteins is limited by high tissue absorption and
      confounding autofluorescence. We previously administered fibroblasts engineered
      to produce BMP-2, but is difficult to determine 3-D information of placement
      prior to bone formation. Herein we used the far-red fluorescence gene reporter,
      IFP1.4 to report the position and viability of fibroblasts and developed 3-D
      tomography to provide placement information. A custom small animal, far-red
      fluorescence tomography system integrated into a commercial CT scanner was used
      to assess IFP1.4 fluorescence and to demark 3-D placement of encapsulated
      fibroblasts with respect to the vertebrae and early bone formation as assessed
      from CT. The results from three experiments showed that the placement of the
      materials within the spine could be detected. This work shows that in vivo
      fluorescence gene reporter tomography of cell-based gene therapy is feasible and
      could help guide cell-based therapies in preclinical models. 

PMID- 24104325
TI  - A merged photonic crystal slot waveguide embedded in ALD-TiO2.
AB  - We demonstrate the concept of a merged nanoscale photonic crystal slot waveguide
      that acts as a bandpass filter in the near infrared region of the spectrum. The
      device is based on the integration of a photonic crystal cavity in a slot
      waveguide on a silicon on insulator substrate. The device is further embedded in
      amorphous titanium dioxide using atomic layer deposition, which allows to reduce
      two-photon absorption losses and creates the possibility to combine nonlinear
      guided-wave optics resulting from the strong field confinement in the slot region
      with slow light effects in the photonic crystal cavity. Our approach is fully
      compatible with complementary metal oxide semiconductor technology and opens up
      new perspectives for the integration of all-optical signal processing
      functionalities in hybrid silicon nanophotonics platforms. 

PMID- 24104326
TI  - Conformal metamaterial absorber for curved surface.
AB  - In this paper, three different unit cells are designed on the basis split-ring
      cross resonators, and each unit cell has an absorption rate greater than 90% at
      incident angles of 0 degrees , 30 degrees , and 45 degrees , respectively. They
      are non-periodically placed in three different zones on the curved surface.
      Therefore, the proposed conformal metamaterial absorber can achieve a high
      absorption rate. The performance of the proposed absorber is compared with that
      of a metallic curved surface and a conformal metamaterial absorber with the same
      unit cells.

PMID- 24104327
TI  - Modeling of the electromagnetic field and level populations in a waveguide
      amplifier: a multi-scale time problem.
AB  - A new algorithm based on auxiliary differential equation and finite difference
      time domain method (ADE-FDTD method) is presented to model a waveguide whose
      active layer is constituted of a silica matrix doped with rare-earth and silicon
      nanograins. The typical lifetime of rare-earth can be as large as some ms,
      whereas the electromagnetic field in a visible range and near-infrared is
      characterized by a period of the order of fs. Due to the large difference between
      these two characteristic times, the conventional ADE-FDTD method is not suited to
      treat such systems. A new algorithm is presented so that the steady state of rare
      earth and silicon nanograins electronic levels populations along with the
      electromagnetic field can be fully described. This algorithm is stable and
      applicable to a wide range of optical gain materials in which large differences
      of characteristic lifetimes are present. 

PMID- 24104328
TI  - Femtosecond laser nanomachining initiated by ultraviolet multiphoton ionization.
AB  - We report on the experimental results of 300 nm features generated on fused
      silica using a near-infrared (IR) femtosecond laser pulse initiated by an
      ultraviolet (UV) pulse. With both pulses at a short (~60 fs) delay, the damage
      threshold of the UV pulse is only 10% of its normal value. Considerable reduction
      of UV damage threshold is observed when two pulses are at +/- 1.3 ps delay. The
      damage feature size of the combined pulses is similar to that of a single UV
      pulse. A modified rate equation model with the consideration of defect states is
      used to help explain these results. This concept can be applied to shorter
      wavelengths, e.g. XUV and X-ray, with the required fluence below their normal
      threshold.

PMID- 24104329
TI  - Mapping the coherence time of far-field speckle scattered by disordered media.
AB  - The polarization and temporal coherence properties of light are altered by
      scattering events. In this paper, we follow a far-field approach, modelizing the
      scattering from disordered media with the scattering matrix formalism. The degree
      of polarization and coherence time of the scattered light are expressed with
      respect to the characteristics of the incident field. 

PMID- 24104330
TI  - The role of stimulated Raman scattering in supercontinuum generation in bulk
      diamond.
AB  - We report on experimental results of supercontinuum generation in bulk diamond.
      The spectrum of supercontinuum generated with 800 nm pump extends up to 600 nm
      towards short wavelengths. We present the numerical model explaining the
      phenomenon, in which the role of different nonlinear effects including stimulated
      Raman scattering is discussed. Unlike in other materials, in diamond the feature
      of supercontinuum due to stimulated Raman response is apparently visible. 

PMID- 24104331
TI  - Reflection-mode optical-resolution photoacoustic microscopy based on a reflective
      objective.
AB  - We developed a new reflection-mode optical-resolution photoacoustic microscopy
      (OR-PAM) based on the cooperation of a reflective objective and an ultrasonic
      transducer. The reflective objective is used to produce nearly diffraction
      limited optical focusing, and the excited ultrasound waves are then directly
      detected by an ultrasonic transducer that was placed in the central cone of the
      objective. This new design avoids the coupling between optical focusing and
      ultrasound transmission in the reflection mode. Moreover, the proposed system is
      able to provide lateral resolution of 1.2 MUm at 580 nm, penetration depth of 0.9
      mm in biological tissues, and a work distance of 6.0 mm. We present in vivo
      imaging of the microvasculature in mouse ears and in vitro imaging of red blood
      cells (RBCs), which demonstrate the capability of the system to study
      microcirculation.

PMID- 24104332
TI  - High sensitivity UV fluorescence spectroscopy based on an optofluidic jet
      waveguide.
AB  - A novel spectroscopic sensor based on an optofluidic liquid jet waveguide is
      presented. In this device, a liquid jet waveguide is generated with the solution
      under analysis. This stream, exploiting total internal reflection, acts as an
      optical waveguide confining the autofluorescence light produced by chemical or
      biological samples when opportunely excited. Using a self-aligned configuration,
      the liquid jet is directly coupled with a multimode optical fiber collecting the
      fluorescence towards the detection system. Experimental measurements have been
      performed using an UV excitation source on water solutions containing
      representative water pollutants as aromatic hydrocarbons or bacteria showing very
      low limit of detection.

PMID- 24104333
TI  - Development of high-density single-mode polymer waveguides with low crosstalk for
      chip-to-chip optical interconnection.
AB  - High-density single-mode polymer waveguides were fabricated for chip-to-chip
      optical interconnection. The waveguides were designed as minimized mode field
      diameters for the lowest inter-channel crosstalk caused by mode coupling. The
      optimum relative index difference chosen was 1.2% to ensure compatibility with
      low crosstalk and wide fabrication tolerances. The 60-mm-length linear waveguides
      demonstrated a low propagation loss of 0.6 dB/cm and -45 dB crosstalk at 1310 nm.
      Also, a new crosstalk mechanism for a curved waveguide was revealed. 

PMID- 24104334
TI  - Semiclassical evaluation of frequency splittings in coupled optical microdisks.
AB  - When two microdisks are placed close to each other and the evanescent fields of
      their whispering gallery modes are overlapped, a strong coupling can be induced
      in the modes and lead to a doublet state. We attempt to evaluate the frequency
      splittings of the doublets by applying a semiclassical analysis in the regime of
      small wavelengths. Since a whispering gallery mode in a microdisk is a leaky
      mode, an established semiclassical method that deals with coupled closed systems
      is modified. As a result, we attain an analytic formula which can conveniently
      compute the frequency splittings of coupled whispering gallery modes. The derived
      formula is verified by demostrating a perfect agreement with numerical solutions
      of Maxwell's equations. 

PMID- 24104335
TI  - Amplified spontaneous emission in graded-index polymer optical fibers: theory and
      experiment.
AB  - In this work we analyze experimentally and theoretically the properties of
      amplified spontaneous emission (ASE) in a rhodamine-6G-doped graded-index polymer
      optical fiber. A theoretical model based on the laser rate equations describes
      the ASE features successfully. The dependence of the ASE threshold and efficiency
      on fiber length is analyzed in detail. 

PMID- 24104336
TI  - Active polarisation control of a quantum cascade laser using tuneable
      birefringence in waveguides.
AB  - We discuss the design, modelling, fabrication and characterisation of an
      integrated tuneable birefringent waveguide for quantum cascade lasers. We have
      fabricated quantum cascade lasers operating at wavelengths around 4450 nm that
      include polarisation mode converters and a differential phase shift section. We
      employed below laser threshold electroluminescence to investigate the single pass
      operation of the integrated device. We use a theory based on the electro-optic
      properties of birefringence in quantum cascade laser waveguides combined with a
      Jones matrix based description to gain an understanding of the
      electroluminescence results. With the quantum cascade lasers operating above
      threshold we demonstrated polarisation control of the output. 

PMID- 24104337
TI  - Mid-infrared ZBLAN fiber supercontinuum source using picosecond diode-pumping at
      2 um.
AB  - We present the first demonstration of mid-IR supercontinuum generation directly
      pumped with picosecond pulses from a Thulium fiber-amplified gain-switched laser
      diode at 2 um. We achieve more than two octaves of bandwidth from 750 - 4000 nm
      in step-index ZBLAN fiber with Watt-level average power and spectral flatness of
      less than 1.5 dB over a 1300 nm range in the mid-IR from 2450 - 3750 nm. The
      system offers high stability, power-scaling capability to the 10 W regime, and
      demonstrates an attractive route towards relatively inexpensive, versatile and
      practical sources of high power broadband mid-IR radiation.

PMID- 24104338
TI  - Reverse polarity optical-OFDM (RPO-OFDM): dimming compatible OFDM for gigabit VLC
      links.
AB  - Visible light communications (VLC) technology permits the exploitation of light
      emitting diode (LED) luminaries for simultaneous illumination and broadband
      wireless communication. Optical orthogonal frequency-division multiplexing (O
      OFDM) is a promising modulation technique for VLC systems, in which the real
      valued O-OFDM baseband signal is used to modulate the instantaneous power of the
      optical carrier to achieve gigabit data rates. However, a major design challenge
      that limits the commercialization of VLC is how to incorporate the industry
      preferred pulse-width modulation (PWM) light dimming technique while maintaining
      a broadband and reliable communication link. In this work, a novel signal format,
      reverse polarity O-OFDM (RPO-OFDM), is proposed to combine the fast O-OFDM
      communication signal with the relatively slow PWM dimming signal, where both
      signals contribute to the effective LED brightness. The advantages of using RPO
      OFDM include, (1) the data rate is not limited by the frequency of the PWM
      signal, (2) the LED dynamic range is fully utilized to minimize the nonlinear
      distortion of the O-OFDM communication signal, and (3) the bit-error performance
      is sustained over a large fraction of the luminaire dimming range. In addition,
      RPO-OFDM offers a practical approach to utilize off-the-shelf LED drivers. We
      show results of numerical simulations to study the trade-offs between the PWM
      duty cycle, average electrical O-OFDM signal power, radiated optical flux as well
      as human perceived light.

PMID- 24104339
TI  - Non-Poissonian formation of multiple excitons in photoexcited CdTe colloidal
      quantum qots by femtosecond nonresonant two-photon absorption.
AB  - Using direct multiexcitonic spectroscopy, we experimentally observe for the first
      time the non-Poissonian formation of multiple excitons by femtosecond nonresonant
      two-photon absorption process in semiconductor colloidal quantum dots (QDs). Each
      of the multiple excitons is individually generated via the absorption of a pair
      of photons during the femtosecond pulse irradiation. The non-Poissonian
      distribution of the generated excitons is reflected as a non-quadratic dependence
      on the pulse intensity of the average number of excitons per QD. This is the main
      observation of the present work. It is explained by a multiexcitonic formation
      model that is based on the phenomenon of intrapulse state filling of the few
      quantum electronic states accessed by the two-photon transitions. The experiments
      are conducted with 3.9-nm CdTe QDs in room-temperature hexane solution using the
      femtosecond pump-probe transient absorption technique, where an intense pump
      pulse generates the excitons and a weak probe pulse measures their number via
      intraband one-photon absorption.

PMID- 24104340
TI  - Above-threshold ionization by few-cycle phase jump pulses.
AB  - We theoretically investigate the above-threshold ionization of hydrogen atoms
      driven by few-cycle phase jump laser pulses. By numerically solving the three
      dimensional time-dependent Schrodinger equation, we demonstrate that the phase
      jump plays an important role in the ionization process. The cutoff of the
      photoelectron energy spectrum can extend to a range of very high energy, and the
      yield of the photoelectrons can be dramatically enhanced by choosing proper phase
      jump times. Both the classical simulations and Fourier transform method are used
      to understand the spectra features found in our investigation.

PMID- 24104341
TI  - Guided-mode resonance enhanced excitation and extraction of two-photon
      photoluminescence in a resonant waveguide grating.
AB  - Guided-mode resonances enhanced excitation and extraction of two-photon
      photoluminescence (TPP) is demonstrated with a one-dimensional resonant waveguide
      grating (RWG) with a layer of fluorescent polymer (polyfluorene, PFO) on top. In
      this work, we design and fabricate a PFO RWG, in which two dispersive resonant
      modes in TE-polarization were measured. By aligning the red-shifting resonant
      mode with excitation wavelength in the infrared range, and the blue-shifting
      resonant mode with TPP spectrum in the visible range, the intensity of TPP can be
      enhanced up to 300-fold compared with that from a flat film with the same
      thickness coated on a glass slide. Such high enhancement results from firstly the
      strong evanescent local field in the waveguide layer due to the resonance between
      the incident light and the waveguide structure according to the results of
      rigorous coupled-wave analysis calculation, and secondly the enhanced extraction
      of the emission light which also resonates with the waveguide structure.

PMID- 24104342
TI  - Dual mode fused optical fiber couplers suitable for mode division multiplexed
      transmission.
AB  - We experimentally demonstrate 2 * 2 and 3 * 3 fused fiber couplers made from dual
      mode fiber. A unique mode dependent power transfer characteristics as a function
      of pulling length is obtained that support various optical functionalities.
      Exploiting this we demonstrate several devices of interest for mode division
      multiplexed data transmission including LP11 mode filter, LP11 mode tap coupler,
      and 50:50 power splitter for both LP01 and LP11 modes.

PMID- 24104343
TI  - Cavity-enhanced spectroscopy of a rare-earth-ion-doped crystal: observation of a
      power law for inhomogeneous broadening.
AB  - We experimentally demonstrate cavity-enhanced spectroscopy of a rare-earth-ion
      doped crystal (Pr3+:Y2SiO5). We succeeded in observing very small absorption due
      to the ions appropriately prepared by optical pumping, which corresponds to the
      single-pass absorption of 4 * 10-6. We also observed a power law for the
      inhomogeneous broadening of optical transitions of ions in the crystal. Compared
      with a theoretical model, the result of the power law indicates that the dominant
      origin of the inhomogeneous broadening may be some charged defects.

PMID- 24104344
TI  - Nonlinear spectral management: linearization of the lossless fiber channel.
AB  - Using the integrable nonlinear Schrodinger equation (NLSE) as a channel model, we
      describe the application of nonlinear spectral management for effective
      mitigation of all nonlinear distortions induced by the fiber Kerr effect. Our
      approach is a modification and substantial development of the so-called
      "eigenvalue communication" idea first presented in A. Hasegawa, T. Nyu, J.
      Lightwave Technol. 11, 395 (1993). The key feature of the nonlinear Fourier
      transform (inverse scattering transform) method is that for the NLSE, any input
      signal can be decomposed into the so-called scattering data (nonlinear spectrum),
      which evolve in a trivial manner, similar to the evolution of Fourier components
      in linear equations. We consider here a practically important weakly nonlinear
      transmission regime and propose a general method of the effective
      encoding/modulation of the nonlinear spectrum: The machinery of our approach is
      based on the recursive Fourier-type integration of the input profile and, thus,
      can be considered for electronic or all-optical implementations. We also present
      a novel concept of nonlinear spectral pre-compensation, or in other terms, an
      effective nonlinear spectral pre-equalization. The proposed general technique is
      then illustrated through particular analytical results available for the
      transmission of a segment of the orthogonal frequency division multiplexing
      (OFDM) formatted pattern, and through WDM input based on Gaussian pulses.
      Finally, the robustness of the method against the amplifier spontaneous emission
      is demonstrated, and the general numerical complexity of the nonlinear spectrum
      usage is discussed.

PMID- 24104345
TI  - Laser induced sponge-like Si in Si-rich oxides for photovoltaics.
AB  - We show that a sponge-like structure of interconnected Si nanowires embedded in a
      dielectric matrix can be obtained by laser annealing of silicon rich oxides
      (SRO). Due to quantum confinement, the large bandgap displayed by these
      percolated nanostructures can be utilized as a tandem stage in 3rd generation
      thin-film solar cells. Well passivated by the SiO2 dielectric matrix, they are
      expected to overcome the difficulty of carrier separation encountered in the case
      of isolated crystalline quantum dots. In this study PECVD grown SRO were
      irradiated by a cw Ar+ laser. Raman spectroscopy has been used to assess the
      crystallinity of the Si nanostructures and thus to optimize the annealing
      conditions as dwell times and power densities. In addition, Si plasmon imaging in
      the transmission electron microscope was applied to identify the sponge-like
      structure of phase-separated silicon.

PMID- 24104346
TI  - Light turning mirrors for hybrid integration of SiON-based optical waveguides and
      photo-detectors.
AB  - For hybrid integration of an optical chip with an electronic chip containing
      photo-diodes and processing electronics, light must be coupled from the optical
      to the electronic chip. This paper presents a method to fabricate quasi-total
      internal-reflecting mirrors on an optical chip, placed at an angle of 45 degrees 
      with the chip surface, that enable 90 degrees  out-of-plane light coupling
      between flip-chip bonded chips. The fabrication method utilizes a metal-free,
      parallel process and is fully compatible with conventional fabrication of optical
      chips. The mirrors are created using anisotropic etching of 45 degrees  facets in
      a Si substrate, followed by fabrication of the optical structures. After removal
      of the mirror-defining Si structures by isotropic etching, the obtained
      interfaces between optical structure and air direct the output from optical
      waveguides to out-of-plane photo-detectors on the electronic chip, which is aimed
      to be flip-chip mounted on the optical chip. For transverse-electric (transverse
      magnetic) polarization simulations predict a functional loss of 7% (15%), while
      7% (18%) is measured.

PMID- 24104347
TI  - Improved generalized regularized phase tracker for demodulation of a single
      fringe pattern.
AB  - A generalized regularized phase tracker (GRPT) for demodulation of a single
      fringe pattern was recently proposed. It is very successful for many fringe
      patterns. However, the GRPT has poor performance in the area where the fringe
      pattern is sparse. An improved GRPT (iGRPT) with two novel improvements is
      proposed to overcome the problem. First, the fixed window used in the GRPT is
      replaced by a spatially adaptive window. Second, a background regularization term
      and a modulation regularization term are incorporated in the cost function. With
      these two improvements, the proposed iGRPT can successfully demodulate sparse
      fringes and thus improves the demodulation capability of the GRPT. Simulation and
      experimental results are presented to verify the performance of the iGRPT.

PMID- 24104348
TI  - Simplified model for optical rectification of broadband terahertz pulses in lossy
      waveguides including a new generalized expression for the coherence length.
AB  - We present a simplified coupled mode theory (CMT), suited for high losses, to
      describe ultra-broadband THz generation through optical rectification (OR) of fs
      infrared pulses in waveguides. We derive a new expression that incorporates loss
      effects into the coherence length for OR. The simplified approach reproduces the
      results of a computationally rigorous integral CMT that must be used for
      broadband THz generation. With the new model we perform a parametric study to
      establish the optimal conditions for OR in symmetric, five-layer,
      metal/cladding/core structures with electro optic polymer cores. We find
      conversion efficiencies as high as 35 * 10-4 W-1 and bandwidths up to 20 THz when
      pumping at 1900 nm. We find that low-loss-cladding layers enhance the efficiency
      for phase-matched structures, increase the interaction length, and improve the
      stability of the efficiency with respect to variations in waveguide parameters.

PMID- 24104349
TI  - Radiation force of abruptly autofocusing Airy beams on a Rayleigh particle.
AB  - The radiation force of circular Airy beams (CAB) on a dielectric Rayleigh
      particle is investigated in this paper. Our results show that the CAB can be used
      to trap the particle whose refractive index is larger than the ambient at
      different positions along the beam axis. Comparing with the Gaussian beam under
      the same conditions, the longitudinal and the transverse gradient force of CAB on
      the Rayleigh particle are increased, and the particle can be trapped more stable.
      Our analyses also demonstrate that the trapping properties of CAB can be
      modulated by controlling corresponding parameters of CAB. 

PMID- 24104350
TI  - Control of ribosome traffic by position-dependent choice of synonymous codons.
AB  - Messenger RNA (mRNA) encodes a sequence of amino acids by using codons. For most
      amino acids, there are multiple synonymous codons that can encode the amino acid.
      The translation speed can vary from one codon to another, thus there is room for
      changing the ribosome speed while keeping the amino acid sequence and hence the
      resulting protein. Recently, it has been noticed that the choice of the
      synonymous codon, via the resulting distribution of slow- and fast-translated
      codons, affects not only on the average speed of one ribosome translating the
      mRNA but also might have an effect on nearby ribosomes by affecting the
      appearance of 'traffic jams' where multiple ribosomes collide and form queues. To
      test this 'context effect' further, we here investigate the effect of the
      sequence of synonymous codons on the ribosome traffic by using a ribosome traffic
      model with codon-dependent rates, estimated from experiments. We compare the
      ribosome traffic on wild-type (WT) sequences and sequences where the synonymous
      codons were swapped randomly. By simulating translation of 87 genes, we
      demonstrate that the WT sequences, especially those with a high bias in codon
      usage, tend to have the ability to reduce ribosome collisions, hence optimizing
      the cellular investment in the translation apparatus. The magnitude of such
      reduction of the translation time might have a significant impact on the cellular
      growth rate and thereby have importance for the survival of the species. 

PMID- 24104351
TI  - Preparation of allylboronates by Pd-catalysed borylative cyclisation of dienynes.
AB  - Reaction of a variety of dienynes with bis(pinacolato)diboron catalysed by Pd
      bis(trifluoroacetate) affords allylic boronates containing five or six membered
      carbo- or heterocycles, by concomitant formation of one C-C and one C-B bonds.
      Resulting allylboronates can be employed for a variety of subsequent
      transformations. 

PMID- 24104352
TI  - Isoangustone A, a novel licorice compound, inhibits cell proliferation by
      targeting PI3K, MKK4, and MKK7 in human melanoma.
AB  - Licorice root is known to possess various bioactivities, including anti
      inflammatory and anticancer effects. Glycyrrhizin, a triterpene compound, is the
      most abundant constituent of dried licorice root. However, high intake or long
      term consumption of glycyrrhizin causes several side effects, such as
      hypertension, hypertensive encephalopathy, and hypokalemia. Therefore, finding
      additional active compounds other than glycyrrhizin in licorice that exhibit
      anticancer effects is worthwhile. We found that isoangustone A (IAA), a novel
      flavonoid from licorice root, suppressed proliferation of human melanoma cells.
      IAA significantly blocked cell-cycle progression at the G1-phase and inhibited
      the expression of G1-phase regulatory proteins, including cyclins D1 and E in the
      SK-MEL-28 human melanoma cell line. IAA suppressed the phosphorylation of Akt,
      GSK-3beta, and JNK1/2. IAA also bound to phosphoinositide 3-kinase (PI3K), MKK4,
      and MKK7, strongly inhibiting their kinase activities in an ATP-competitive
      manner. Moreover, in a xenograft mouse model, IAA significantly decreased tumor
      growth, volume, and weight of SK-MEL-28 xenografts. Collectively, these results
      suggest that PI3K, MKK4, and MKK7 are the primary molecular targets of IAA in the
      suppression of cell proliferation. This insight into the biologic actions of IAA
      provides a molecular basis for the potential development of a new
      chemotherapeutic agent.

PMID- 24104353
TI  - Esculetin suppresses proliferation of human colon cancer cells by directly
      targeting beta-catenin.
AB  - The Wnt pathway is a promising therapeutic and preventive target in various human
      cancers. The transcriptional complex of beta-catenin-T-cell factor (Tcf), a key
      mediator of canonical Wnt signaling, has been implicated in human colon cancer
      development. Current treatment of colon cancer depends on traditional cytotoxic
      agents with limited effects. Therefore, the identification of natural compounds
      that can disrupt the beta-catenin-TcF complex to suppress cancer cell growth with
      fewer adverse side effects is needed. To identify compounds that inhibit the
      association between beta-catenin and Tcf, we used computer docking to screen a
      natural compound library. Esculetin, also known as 6,7-dihydroxycoumarin, is a
      derivative of coumarin and was identified as a potential small-molecule inhibitor
      of the Wnt-beta-catenin pathway. We then evaluated the effect of esculetin on the
      growth of various human colon cancer cell lines and its effect on Wnt-beta
      catenin signaling in cells and in an embryonic model. Esculetin disrupted the
      formation of the beta-catenin-Tcf complex through direct binding with the Lys312,
      Gly307, Lys345, and Asn387 residues of beta-catenin in colon cancer cells. In
      addition, esculetin effectively decreased viability and inhibited anchorage
      independent growth of colon cancer cells. Esculetin potently antagonized the
      cellular effects of beta-catenin-dependent activity, and in vivo treatment with
      esculetin suppressed tumor growth in a colon cancer xenograft mouse model. Our
      data indicate that the interaction between esculetin and beta-catenin inhibits
      the formation of the beta-catenin-Tcf complex, which could contribute to
      esculetin's positive therapeutic and preventive effects against colon
      carcinogenesis.

PMID- 24104357
TI  - Study, North Conway, New Hampshire: David Johnson.

PMID- 24104358
TI  - SAMHSA: Pain medication abuse a common path to heroin: experts say this pattern
      likely driving heroin resurgence.

PMID- 24104354
TI  - The involvement of endoplasmic reticulum stress in the suppression of colorectal
      tumorigenesis by tolfenamic acid.
AB  - The nonsteroidal anti-inflammatory drug tolfenamic acid has been shown to
      suppress cancer cell growth and tumorigenesis in different cancer models.
      However, the underlying mechanism by which tolfenamic acid exerts its
      antitumorigenic effect remains unclear. Previous data from our group and others
      indicate that tolfenamic acid alters expression of apoptosis- and cell-cycle
      arrest-related genes in colorectal cancer cells. Here, we show that tolfenamic
      acid markedly reduced the number of polyps and tumor load in APC(min)(/+) mice,
      accompanied with cyclin D1 downregulation in vitro and in vivo. Mechanistically,
      tolfenamic acid promotes endoplasmic reticulum (ER) stress, resulting in
      activation of the unfolded protein response (UPR) signaling pathway, of which
      PERK-mediated phosphorylation of eukaryotic translation initiation factor 2alpha
      (eIF2alpha) induces the repression of cyclin D1 translation. Moreover, the PERK
      eIF2alpha-ATF4 branch of the UPR pathway plays a role in tolfenamic acid-induced
      apoptosis in colorectal cancer cells, as silencing ATF4 attenuates tolfenamic
      acid-induced apoptosis. Taken together, these results suggest ER stress is
      involved in tolfenamic acid-induced inhibition of colorectal cancer cell growth,
      which could contribute to antitumorigenesis in a mouse model.

PMID- 24104359
TI  - FDA advisory panel recommends approval of drug for preoperative treatment of
      breast cancer.

PMID- 24104360
TI  - New drugs improve glycemic control in type 2 diabetes, but improving heart health
      remains elusive.

PMID- 24104361
TI  - AHA: Severe obesity in US youth is increasing and difficult to treat.

PMID- 24104371
TI  - A piece of my mind. As if he were family.

PMID- 24104372
TI  - Adjuvant chemotherapy with gemcitabine and long-term outcomes among patients with
      resected pancreatic cancer: the CONKO-001 randomized trial.
AB  - IMPORTANCE: The prognosis for patients with pancreatic cancer is poor, even after
      resection with curative intent. Gemcitabine-based chemotherapy is standard
      treatment for advanced pancreatic cancer, but its effect on survival in the
      adjuvant setting has not been demonstrated. OBJECTIVE: To analyze whether
      previously reported improvement in disease-free survival with adjuvant
      gemcitabine therapy translates into improved overall survival. DESIGN, SETTING,
      AND PATIENTS: CONKO-001 (Charite Onkologie 001), a multicenter, open-label, phase
      3 randomized trial to evaluate the efficacy and toxicity of gemcitabine in
      patients with pancreatic cancer after complete tumor resection. Patients with
      macroscopically completely removed pancreatic cancer entered the study between
      July 1998 and December 2004 in 88 hospitals in Germany and Austria. Follow-up
      ended in September 2012. INTERVENTIONS: After stratification for tumor stage,
      nodal status, and resection status, patients were randomly assigned to either
      adjuvant gemcitabine treatment (1g/m2 d 1, 8, 15, q 4 weeks) for 6 months or to
      observation alone. MAIN OUTCOMES AND MEASURES: The primary end point was disease
      free survival. Secondary end points included treatment safety and overall
      survival, with overall survival defined as the time from date of randomization to
      death. Patients lost to follow-up were censored on the date of their last follow
      up. RESULTS: A total of 368 patients were randomized, and 354 were eligible for
      intention-to-treat-analysis. By September 2012, 308 patients (87.0% [95% CI,
      83.1%-90.1%]) had relapsed and 316 patients (89.3% [95% CI, 85.6%-92.1%]) had
      died. The median follow-up time was 136 months. The median disease-free survival
      was 13.4 (95% CI, 11.6-15.3) months in the treatment group compared with 6.7 (95%
      CI, 6.0-7.5) months in the observation group (hazard ratio, 0.55 [95% CI, 0.44
      0.69]; P < .001). Patients randomized to adjuvant gemcitabine treatment had
      prolonged overall survival compared with those randomized to observation alone
      (hazard ratio, 0.76 [95% CI, 0.61-0.95]; P = .01), with 5-year overall survival
      of 20.7% (95% CI, 14.7%-26.6%) vs 10.4% (95% CI, 5.9%-15.0%), respectively, and
      10-year overall survival of 12.2% (95% CI, 7.3%-17.2%) vs 7.7% (95% CI, 3.6%
      11.8%). CONCLUSIONS AND RELEVANCE: Among patients with macroscopic complete
      removal of pancreatic cancer, the use of adjuvant gemcitabine for 6 months
      compared with observation alone resulted in increased overall survival as well as
      disease-free survival. These findings provide strong support for the use of
      gemcitabine in this setting. TRIAL REGISTRATION: isrctn.org Identifier:
      ISRCTN34802808.

PMID- 24104373
TI  - Asymptomatic aortic stenosis in the elderly: a clinical review.
AB  - IMPORTANCE: Aortic stenosis is the most common form of valvular heart disease.
      Progression of aortic stenosis is very slow and highly variable. Decisions about
      when to perform valve surgery are made by subjective assessment of patient
      symptoms and objective measures of the valve and ventricular function by
      transthoracic echocardiography. OBJECTIVE: To review current concepts regarding
      the development, progression, and assessment of aortic stenosis; the appropriate
      monitoring intervals for transthoracic echocardiography; and the indications for
      valve procedures. EVIDENCE REVIEW: Guidelines and literature search. FINDINGS:
      Angina, exertional syncope, and heart failure are key symptoms indicating a need
      for intervention. The frequency of valvular monitoring by transthoracic
      echocardiography is guided by the disease severity. Despite evidence of severe
      disease, valve procedures can safely be deferred if patients experience no
      symptoms and have normal left ventricular ejection fraction. Asymptomatic
      patients with severe aortic stenosis may subconsciously curtail their activities
      to avoid symptoms. Apparently, asymptomatic patients can undergo a carefully
      monitored exercise stress test to confirm both their asymptomatic status and
      hemodynamic response to exercise. Bioprosthetic valves are a good replacement
      alternative for older patients who are good surgical candidates and who have no
      need for warfarin therapy. For patients who are at high or very high risk of
      cardiac surgery, transcutaneous aortic valve implantation is an increasing
      available and preferred over medical management. CONCLUSIONS AND RELEVANCE:
      Asymptomatic patients with severe aortic stenosis require frequent monitoring of
      their subjective symptoms combined with objective measurement of aortic valve
      gradient and ventricular function by transthoracic echocardiography. Although
      conventional surgical replacement remains the mainstay of therapy for aortic
      stenosis, transcutaneous aortic valve implantation options are evolving.

PMID- 24104374
TI  - Abnormal gallbladder finding in a septic patient with blood loss.

PMID- 24104375
TI  - Single- vs multiple-fraction radiotherapy for bone metastases from prostate
      cancer.

PMID- 24104376
TI  - Assays for cardiac troponins.

PMID- 24104377
TI  - Assays for cardiac troponins--reply.

PMID- 24104378
TI  - Nonadherence to medications.

PMID- 24104379
TI  - Nonadherence to medications.

PMID- 24104380
TI  - Nonadherence to medications.

PMID- 24104381
TI  - Nonadherence to medications.

PMID- 24104382
TI  - Nonadherence to medications--reply.

PMID- 24104385
TI  - The senses of taste and smell. October 4, 1913.

PMID- 24104386
TI  - JAMA patient page. Breast cancer and axillary lymph nodes.

PMID- 24104387
TI  - Toxicological effects of multi-walled carbon nanotubes adsorbed with nonylphenol
      on earthworm Eisenia fetida.
AB  - The high surface area of multi-walled carbon nanotubes (MWCNTs) tends to adsorb a
      large variety of toxic chemicals, which may enhance the toxicity of both MWCNTs
      and chemicals to organisms. In order to evaluate the combined toxicity of
      nonylphenol (NP) and MWCNTs to the earthworm Eisenia fetida in soil, artificial
      soil systems containing distilled water, 0.1 g kg(-1) MWCNTs, 1 g kg(-1) MWCNTs,
      1 g kg(-1) MWCNTs absorbed 5 mg kg(-1) NP, and 10 mg kg(-1) NP alone were
      prepared and exposed to earthworms for 7 days. Antioxidative responses, and
      activities of cellulase, Na(+), K(+)-ATPase and acetylcholinesterase (TChE) as
      well as DNA damage were chosen as toxicological endpoints. The results showed
      that 1 g kg(-1) MWCNTs adsorbed 5 mg kg(-1) NP from the soil which caused much
      more adverse effects on the earthworms than each chemical alone, evident from the
      responses of cellulase, Na(+), K(+)-ATPase and comet assay. This study indicated
      that MWCNTs facilitated the bioavailability of NP to the earthworm and increased
      the harmful effects of NP. 

PMID- 24104388
TI  - Primary aldosteronism: a new insight into pathogenesis, diagnosis, and treatment
      in hypertensive patients.
AB  - Primary aldosteronism (PA) seems to be a pathogenetically heterogenous disease.
      It is suggested that approximately 30% of all hypertensive patients are affected
      by this disease. Autonomous hypersecretion of aldosterone, which is observed in
      this patient group, may be caused by an adrenal adenoma (aldosteronoma),
      hyperplasia of the zona glomerulosa, mutation of the KCNJ5 potassium channel, or
      other rare pathogenetic factors. Contrary to what was believed before, PA may be
      the cause of resistant hypertension rather than mild hypertension, while 70% of
      the patients have normal serum potassium levels rather than hypokalemia
      (previously believed to be a classical PA symptom). Hypertensive patients with
      normal or elevated aldosteronemia (A), suppressed plasma renin activity (PRA) and
      an elevated A/PRA ratio should undergo further diagnostic work-up for PA. PA is
      suspected to be the continuum of low-renin hypertension. First-choice therapy of
      PA should be based on long-term administration of low-dose mineralocorticoid
      receptor antagonists (spironolactone, eplerenone) and, in the nearest future,
      probably also aldosterone synthase antagonists such as CLI699, regardless of the
      morphological type of PA. It is still unknown whether pharmacological treatment
      will totally replace surgical treatment in some types of PA. Long-term
      administration of low-dose aldosterone antagonists is an effective and often
      underscored antihypertensive treatment, which rarely causes serious hyperkalemia
      if the kidney function is not impaired.

PMID- 24104389
TI  - The diagnostic classification of eating disorders: current situation, possible
      alternatives and future perspectives.
AB  - The current nosography of eating disorders (ED) has various limitations in terms
      of validity and accuracy. The changes adopted in the DSM-5 limit some of the
      current problems, such as excessive prevalence of ED not otherwise specified
      (EDNOS) and the lack of longitudinal stability, but are unlikely to adequately
      capture the clinical complexity of ED. Many authors suggest the need for a
      thorough review of the current nosography to support evidence-based
      classification. In this paper, we discuss the validity of the current diagnostic
      categories and their possible reorganization. Furthermore, we review the main
      empirical models of classification and the diagnostic approach from a personality
      perspective, with particular attention to research and to the prognostic and
      therapeutic implications. 

PMID- 24104390
TI  - DNA methylome: Unveiling your biological age.
AB  - Hannum and colleagues performed DNA methylation sequencing to examine the
      relationship between DNA methylome and aging rate. Notably, they succeeded in
      building a quantitative and reproducible model based on the epigenetic bio
      markers to predict aging rate with high accuracy. This progress enlightens us in
      many aspects particularly in applying this novel set of bio-markers on studying
      the mechanism of aging rate using adult tissue-specific stem cells, building up a
      potential quantitative model to explore the mechanism for other epigenetic
      factors like non-coding RNA, and understanding the principle and mechanism of 3D
      chromatin structure in epigenetic modulation.

PMID- 24104391
TI  - Protein dynamics elucidated by NMR technique.

PMID- 24104392
TI  - Identification and functional analysis of phosphorylation residues of the
      Arabidopsis BOTRYTIS-INDUCED KINASE1.
AB  - Arabidopsis BOTRYTIS-INDUCED KINASE1 (BIK1) is a receptor-like cytoplasmic kinase
      acting early in multiple signaling pathways important for plant growth and innate
      immunity. It is known to form a signaling complex with a cell-surface receptor
      FLS2 and a co-receptor kinase BAK1 to transduce signals upon perception of
      pathogen-associated molecular patterns (PAMPs). Although site-specific
      phosphorylation is speculated to mediate the activation and function of BIK1, few
      studies have been devoted to complete profiling of BIK1 phosphorylation residues.
      Here, we identified nineteen in vitro autophosphorylation sites of BIK1 including
      three phosphotyrosine sites, thereby proving BIK1 is a dual-specificity kinase
      for the first time. The kinase activity of BIK1 substitution mutants were
      explicitly assessed using quantitative mass spectrometry (MS). Thr-237, Thr-242
      and Tyr-250 were found to most significantly affect BIK1 activity in
      autophosphorylation and phosphorylation of BAK1 in vitro. A structural model of
      BIK1 was built to further illustrate the molecular functions of specific
      phosphorylation residues. We also mapped new sites of FLS2 phosphorylation by
      BIK1, which are different from those by BAK1. These in vitro results could
      provide new hypotheses for more in-depth in vivo studies leading to deeper
      understanding of how phosphorylation contributes to BIK1 activation and mediates
      downstream signaling specificity.

PMID- 24104393
TI  - Structural basis for a homodimeric ATPase subunit of an ECF transporter.
AB  - The transition metal cobalt, an essential cofactor for many enzymes in
      prokaryotes, is taken up by several specific transport systems. The CbiMNQO
      protein complex belongs to type-1 energy-coupling factor (ECF) transporters and
      is a widespread group of microbial cobalt transporters. CbiO is the ATPase
      subunit (A-component) of the cobalt transporting system in the gram-negative
      thermophilic bacterium Thermoanaerobacter tengcongensis. Here we report the
      crystal structure of a nucleotide-free CbiO at a resolution of 2.3 A. CbiO
      contains an N-terminal canonical nucleotide-binding domain (NBD) and C-terminal
      helical domain. Structural and biochemical data show that CbiO forms a homodimer
      mediated by the NBD and the C-terminal domain. Interactions mainly via conserved
      hydrophobic amino acids between the two C-terminal domains result in formation of
      a four-helix bundle. Structural comparison with other ECF transporters suggests
      that non-conserved residues outside the T-component binding groove in the A
      component likely act as a specificity determinant for T components. Together, our
      data provide information on understanding of the structural organization and
      interaction of the CbiMNQO system.

PMID- 24104394
TI  - MicroRNA187 overexpression is related to tumor progression and determines
      sensitivity to bortezomib in peripheral T-cell lymphoma.
AB  - MicroRNAs (miRs) are involved in tumorigenesis by regulating tumor suppressor
      genes and/or oncogenes. MiR187 was overexpressed in peripheral T-cell lymphoma,
      not otherwise specified (PTCL-NOS) and associated with high Ki67 expression,
      elevated lactate dehydrogenase, advanced International Prognostic Index and poor
      prognosis of patients. In vitro, ectopic expression of miR187 in T-lymphoma cell
      lines accelerated tumor cell proliferation, whereas treatment with miR187
      inhibitor reduced cell growth. MiR187 downregulated tumor suppressor gene
      disabled homolog-2 (Dab2), decreased the interaction of Dab2 with adapter protein
      Grb2, resulting in Ras activation, phosphorylation/activation of extracellular
      signal-regulated kinase (ERK) and AKT, and subsequent stabilization of MYC
      oncoprotein. MiR187-overexpressing cells were resistant to chemotherapeutic
      agents like doxorubicin, cyclophosphamide, cisplatin and gemcitabine, but
      sensitive to the proteasome inhibitor bortezomib. Bortezomib inhibited T-lymphoma
      cell proliferation by downregulating miR187, dephosphorylating ERK and AKT and
      degrading MYC. In a murine xenograft model established with subcutaneous
      injection of Jurkat cells, bortezomib particularly retarded the growth of miR187
      overexpressing tumors, consistent with the downregulation of miR187, Ki67 and MYC
      expression. Collectively, these findings indicated that miR187 was related to
      tumor progression in PTCL-NOS through modulating Ras-mediated ERK/AKT/MYC axis.
      Although potentially oncogenic, miR187 indicated the sensitivity of T-lymphoma
      cells to bortezomib. Cooperatively targeting ERK and AKT could be a promising
      clinical strategy in treating MYC-driven lymphoid malignancies. 

PMID- 24104395
TI  - Differences in outcomes of newly diagnosed acute myeloid leukemia for
      adolescent/young adult and younger patients: a report from the Children's
      Oncology Group.
AB  - BACKGROUND: Studies comparing survival of adolescent and young adult (AYA)
      patients to that of younger patients with newly diagnosed acute myeloid leukemia
      (AML) have yielded conflicting results. In order to more accurately characterize
      relative survival and other outcomes of AYA patients, a cross-study analysis was
      conducted using data from recent trials conducted by the Children's Cancer Group
      (CCG) and Children's Oncology Group (COG). METHODS: Data were combined from the
      CCG-2891, CCG-2941, CCG-2961, and AAML03P1 trials. The data set included 1840
      patients, comprising 238 AYA and 1602 younger patients. RESULTS: Overall survival
      was not significantly different in the 2 groups (AYA, 49% +/- 7% versus younger,
      54% +/- 3% (+/- 2 standard errors), P = .058). Relapse was lower in AYA patients
      (30% +/- 7% versus 41% +/- 3%, P = .002), but treatment-related mortality (TRM)
      was higher (25% +/- 6% versus 12% +/- 2%, P < .001). After adjustment for other
      factors, older age remained strongly associated with TRM (hazard ratio = 2.30,
      95% CI = 1.59-3.33, P < .001). Infection accounted for the excess TRM in AYA
      patients. CONCLUSIONS: Survival in AYA and younger patients with newly diagnosed
      AML is similar; however, older patients are at higher risk for TRM. More
      effective strategies for preventing mortality from infection in AYA patients are
      needed.

PMID- 24104396
TI  - Deep transcriptome sequencing of wild halophyte rice, Porteresia coarctata,
      provides novel insights into the salinity and submergence tolerance factors.
AB  - Porteresia coarctata is a wild relative of rice with capability of high salinity
      and submergence tolerance. The transcriptome analyses of Porteresia can lead to
      the identification of candidate genes involved in salinity and submergence
      tolerance. We sequenced the transcriptome of Porteresia under different
      conditions using Illumina platform and generated about 375 million high-quality
      reads. After optimized assembly, a total of 152 367 unique transcript sequences
      with average length of 794 bp were obtained. Many of these sequences might
      represent fragmented transcripts. Functional annotation revealed the presence of
      genes involved in diverse cellular processes and 2749 transcription factor (TF)
      encoding genes in Porteresia. The differential gene expression analyses
      identified a total of 15 158 genes involved in salinity and/or submergence
      response(s). The stress-responsive members of different TF families, including
      MYB, bHLH, AP2-EREBP, WRKY, bZIP and NAC, were identified. We also revealed key
      metabolic pathways, including amino acid biosynthesis, hormone biosynthesis,
      secondary metabolite biosynthesis, carbohydrate metabolism and cell wall
      structures, involved in stress tolerance in Porteresia. The transcriptome
      analyses of Porteresia are expected to highlight genes/pathways involved in
      salinity and submergence tolerance of this halophyte species. The data can serve
      as a resource for unravelling the underlying mechanism and devising strategies to
      engineer salinity and submergence tolerance in rice. 

PMID- 24104398
TI  - Predicting substrate specificity of adenylation domains of nonribosomal peptide
      synthetases and other protein properties by latent semantic indexing.
AB  - Successful genome mining is dependent on accurate prediction of protein function
      from sequence. This often involves dividing protein families into functional
      subtypes (e.g., with different substrates). In many cases, there are only a small
      number of known functional subtypes, but in the case of the adenylation domains
      of nonribosomal peptide synthetases (NRPS), there are >500 known substrates.
      Latent semantic indexing (LSI) was originally developed for text processing but
      has also been used to assign proteins to families. Proteins are treated as
      ''documents'' and it is necessary to encode properties of the amino acid sequence
      as ''terms'' in order to construct a term-document matrix, which counts the terms
      in each document. This matrix is then processed to produce a document-concept
      matrix, where each protein is represented as a row vector. A standard measure of
      the closeness of vectors to each other (cosines of the angle between them)
      provides a measure of protein similarity. Previous work encoded proteins as
      oligopeptide terms, i.e. counted oligopeptides, but used no information regarding
      location of oligopeptides in the proteins. A novel tokenization method was
      developed to analyze information from multiple alignments. LSI successfully
      distinguished between two functional subtypes in five well-characterized
      families. Visualization of different ''concept'' dimensions allows exploration of
      the structure of protein families. LSI was also used to predict the amino acid
      substrate of adenylation domains of NRPS. Better results were obtained when
      selected residues from multiple alignments were used rather than the total
      sequence of the adenylation domains. Using ten residues from the substrate
      binding pocket performed better than using 34 residues within 8 A of the active
      site. Prediction efficiency was somewhat better than that of the best published
      method using a support vector machine.

PMID- 24104397
TI  - Rotenone induces reductive stress and triacylglycerol deposition in C2C12 cells.
AB  - Environmental rotenone is associated with Parkinson's disease due to its
      inhibitory property to the complex I of mitochondrial respiration chain. Although
      environmental pollution has been postulated as a causal factor for the increasing
      prevalence of obesity, the role of rotenone in the pathogenesis of obesity has
      not been studied. We employed muscle-derived cell C2C12 as a model and shotgun
      lipidomics as a tool for lipid analysis and found that treatment with rotenone
      led to the profound deposition of intracellular triacylglycerol (TAG) in a time-
      and dose-dependent fashion. The TAG deposition resulted from complex I
      inhibition. Further studies revealed that rotenone induced mitochondrial stress
      as shown by decreased mitochondrial oxygen consumption rate, increased NADH/NAD+
      ratio (i.e., reductive stress) and mitochondrial metabolites. We demonstrated
      that rotenone activated fatty acid de novo synthesis and TAG synthesis and
      ultimately resulted in intracellular TAG deposition. These studies suggested that
      increased mitochondrial stresses might be an underlying mechanism responsible for
      TAG accumulation manifest in obesity. 

PMID- 24104399
TI  - Challenges and triumphs to genomics-based natural product discovery.
AB  - Genome sequencing is rapidly changing the field of natural products research by
      providing opportunities to assess the biosynthetic potential of strains prior to
      chemical analysis or biological testing. Ready access to sequence data is driving
      the development of new bioinformatic tools and methods to identify the products
      of silent or cryptic pathways. While genome mining has fast become a useful
      approach to natural product discovery, it has also become clear that identifying
      pathways of interest is much easier than finding the associated products. This
      has led to bottlenecks in the discovery process that must be overcome for the
      potential of genomics-based natural product discovery to be fully realized. In
      this perspective, we address some of these challenges in the context of our work
      with the marine actinomycete genus Salinispora, which is proving to be a useful
      model with which to apply genome mining as an approach to natural product
      discovery. 

PMID- 24104401
TI  - Raising the performance of a 4 V supercapacitor based on an EMIBF4-single walled
      carbon nanotube nanofluid electrolyte.
AB  - Addition of a single walled carbon nanotube in ionic liquids of EMIBF4 produced a
      nanofluid with increased ionic conductivity. It, as the electrolyte, allowed the
      increase of the capacitance, energy density and cycling stability of a
      supercapacitor operated at 4 V. 

PMID- 24104400
TI  - Stress in multiple sclerosis: review of new developments and future directions.
AB  - In the experimental autoimmune encephalitis model of multiple sclerosis, the
      effects of stress on disease severity depend on multiple factors, including the
      animal's genetics and the type of stressor. The studies in humans relating stress
      to the risk of developing multiple sclerosis have found discordant results. The
      studies looking at the association of stress with relapses show a fairly
      consistent association, where higher stress is associated with a higher risk of
      relapse. Higher stress levels also appear to increase the risk of development of
      gadolinium-enhancing lesions. A recent randomized trial shows that reducing
      stress using stress management therapy (SMT), a cognitive-behavioral therapy
      approach, results in a statistically significant reduction in new magnetic
      resonance imaging lesions. The magnitude of this effect is large and comparable
      to the effects of existent disease-modifying therapies, but no data exist yet
      proving that SMT reduces relapses or clinical progression; the effect of SMT
      appears to be short-lived. Additional work is needed to improve the duration of
      this effect and make this therapy more widely accessible. 

PMID- 24104402
TI  - Ultrasound elastography in children: establishing the normal range of muscle
      elasticity.
AB  - BACKGROUND: Ultrasound elastography allows assessment of tissue elasticity. To
      the best of our knowledge, the elastography appearance of muscles in normal
      children has not been described. OBJECTIVE: To determine the US elasticity of
      muscles in children at rest and following exercise. MATERIALS AND METHODS: Cine
      elastography of biceps brachii and rectus femoris muscles was obtained at rest
      and after exercise in 42 healthy children (23 males, 19 females; mean: 11.2 +/-
      4.4 years, range: 2-18 years). Elastography scores were assigned to each clip
      based on a five-point color scale. Mean elastography scores and standard
      deviations were calculated and resting and postexercise elastography scores were
      compared. RESULTS: Resting muscle elasticity was lower in the biceps brachii than
      in the rectus femoris (P = 0.008), and higher in the dominant than in the
      nondominant biceps brachii (P < 0.032). Rectus femoris elasticity was higher in
      males than females (P = 0.051). Postexercise muscle elasticity significantly
      increased in both the dominant and nondominant biceps brachii (P < 0.001) and in
      the rectus femoris (P < 0.001). There was no significant gender-related
      difference in postexercise muscle elasticity. Biceps brachii elasticity decreased
      and rectus femoris elasticity increased with increasing body mass index. Younger
      subjects had a greater change in muscle elasticity with exercise. CONCLUSION:
      Resting muscle elasticity in children is significantly lower in the biceps
      brachii than in the rectus femoris and in the nondominant biceps brachii than in
      the dominant biceps brachii. Elasticity significantly increases immediately
      postexercise in both muscle groups; resting differences between biceps brachii
      and rectus femoris elasticity, and dominant and nondominant biceps brachii
      elasticity, do not persist after exercise. The change in muscle elasticity with
      exercise is higher in younger children.

PMID- 24104405
TI  - Local accumulation time for the formation of morphogen gradients from a Levy
      diffusion process.
AB  - Morphogen gradients provide very precise spatial information on the control of
      cell fate specification in many developing tissues. In previous studies,
      morphogen gradient formation was commonly modelled as Fickian diffusion. However,
      the complexity of morphogen transport and anisotropy of intracellular and
      extracellular environments in vivo can lead to Levy flights of morphogens. In
      this case, a natural question is whether morphogen gradients reach steady states
      on timescales relevant to developmental patterning. Here, we build and analyse a
      Levy diffusion model of morphogen transport, which is based on a continuous time
      random walk with a long-tailed jump length distribution. Importantly, we derive
      the analytical expression of local accumulation time that provides a time scale
      that characterizes relaxation to a steady state at an arbitrary position within
      the patterned field, and shows that this time depends on cell positions in a
      nonlinear and asymmetric manner. Our analytical result provides an explicit
      connection between the key parameters of the problem and the time needed to reach
      a steady state value at an arbitrarily given position, which is important for a
      better understanding of tissue patterning by morphogen gradients in a more real
      case. 

PMID- 24104404
TI  - Nlgn4 knockout induces network hypo-excitability in juvenile mouse somatosensory
      cortex in vitro.
AB  - Neuroligins (Nlgns) are postsynaptic cell adhesion molecules that form
      transynaptic complexes with presynaptic neurexins and regulate synapse maturation
      and plasticity. We studied the impact of the loss of Nlgn4 on the excitatory and
      inhibitory circuits in somatosensory cortical slices of juvenile mice by
      electrically stimulating these circuits using a multi-electrode array and
      recording the synaptic input to single neurons using the patch-clamp technique.
      We detected a decreased network response to stimulation in both excitatory and
      inhibitory circuits of Nlgn4 knock-out animals as compared to wild-type controls,
      and a decreased excitation-inhibition ratio. These data indicate that Nlgn4 is
      involved in the regulation of excitatory and inhibitory circuits and contributes
      to a balanced circuit response to stimulation. 

PMID- 24104406
TI  - Effect of a lifestyle therapy program using cardiac rehabilitation resources on
      metabolic syndrome components.
AB  - PURPOSE: To assess the effect of a lifestyle therapy program using cardiac
      rehabilitation (CR) resources for patients at risk for metabolic syndrome (MetS).
      METHODS: We designed a cardiometabolic program (CMP) using CR facilities and
      resources. We compared MetS components of 240 patients classified as either obese
      (body mass index, >=30 kg/m) or hyperglycemic (fasting glucose, >100 mg/dL): 58
      enrolled and completed the CMP, 59 signed up for the CMP but never attended or
      dropped out early (control 1) but had followup data, and 123 did not sign up for
      the CMP (control 2). RESULTS: The CMP group showed a significant improvement at 6
      weeks in waist circumference, body weight, diastolic blood pressure, and total
      cholesterol. At 6 months, fasting glucose also improved. In contrast,
      improvements in control 1 and control 2 were modest at best. Comparing the 6
      month changes in the CMP group versus control 1 group, those in the CMP had
      pronounced weight loss (-4.5 +/- 5 kg vs. -0.14 +/- 6 kg; P < .001), decreased
      systolic blood pressure (-1.1 +/- 17 mm Hg vs. +9.6 +/- 20 mm Hg; P = .004), and
      decreased diastolic blood pressure (-4.6 +/- 11 mm Hg vs. +3.4 +/- 15 mm Hg; P =
      .002). Similarly, comparing CMP group versus control 2 group, body weight (-4.5
      +/- 5 kg vs. -0.9 +/- 3 kg; P < .001) and diastolic blood pressure (-4.6 +/- 11
      mm Hg vs. -0.7 +/- 9 mm Hg; P = .02) declined in the CMP group. CONCLUSION: A
      lifestyle therapy program using resources of a CR program is effective for
      individuals who have or are at risk for MetS, although enrollment and completion
      rates are low.

PMID- 24104407
TI  - Daily steps threshold to improve cardiovascular disease risk factors during the
      year after an acute coronary syndrome.
AB  - PURPOSE: To evaluate the daily steps threshold associated with improved
      cardiovascular disease risk factors during the first year following an acute
      coronary syndrome. METHODS: Subjects (N = 41) were recruited during
      hospitalization for an acute coronary syndrome. A blinded pedometer with a 7-day
      memory (NL-2000) was used at baseline, 3, 6, 9, and 12 months following
      hospitalization. Cardiovascular disease risk factors were measured at baseline,
      6, and 12 months after discharge. Subjects who maintained a mean of 7500 steps
      per day or more at each time period were classified into the active group,
      whereas those who did not maintain this threshold were classified into the less
      active group. RESULTS: The active group included 25 subjects, whereas 16 subjects
      were included in the less active group. Daily steps mean +/- SEM was different
      between groups at 6 and 12 months followup (11 320 +/- 3380 vs 5503 +/- 1502 and
      10 507 +/- 2861 vs 6624 +/- 3295 steps per day, respectively; both P < .001).
      Based on the analysis of variance for repeated measures (ANOVA-RM), the active
      group showed lower triglycerides (P < .01), lower waist circumference (P < .01),
      and higher high-density lipoprotein-cholesterol (HDL-C) (P = .04) at 12 months.
      Interaction effects (group * followup) were also significant for HDL-C (P = .01)
      and triglycerides (P = .01) after adjustment for age, gender, and baseline waist
      circumference. CONCLUSION: Targeting $7500 daily steps during 1 year may be
      efficient to maintain lowest waist circumference and to improve lipid profile
      during the year following an acute coronary syndrome. It could be considered a
      starting target point to initiate changes in physical activity behavior.

PMID- 24104408
TI  - Hematopoietic stem cell transplantation activity in Europe.
AB  - PURPOSE OF REVIEW: This review describes the current use of hematopoietic stem
      cell transplantation (HSCT) and aims to assess recent trends, to analyze factors
      associated with use and trends, and to discuss potential implications of such
      developments on future use. RECENT FINDINGS: The one millionth HSCT worldwide was
      announced in early 2013. More than 35 000 HSCT (40% allogeneic and 60%
      autologous) were reported in 2011 to the European Group for Blood and Marrow
      Transplantation, with more than 60 000 worldwide. Total numbers increased in
      Europe over the last 10 years by 50%, with the highest increase being for
      allogeneic HSCT from an unrelated donor. Change in HSCT numbers was different for
      each indication with novel indications emerging. There were significant
      differences in absolute numbers and increase in transplant rates between
      countries concerning main indication, donor type, and stem cell source or
      transplant technology. Trends showed a widening gap between countries with high
      or low national income. The high costs of HSCT impact on its use; availability of
      resources, presence of a national registry, and numbers of registered donors are
      the most closely associated with unrelated donor transplant rates. SUMMARY:
      Timely and comprehensive data on HSCT activity reveal trends and provide
      essential information for decision making to patients, physicians, healthcare
      administrators, or competent authorities alike.

PMID- 24104410
TI  - Stem cell transplantation for primary immune deficiency.
AB  - PURPOSE OF REVIEW: In this article, we summarize the recent advances in treating
      primary immune deficiency (PID) disorders by stem cell transplantation (SCT); we
      have focused on articles published in the past 2 years since the last major
      review of SCT for PID. RECENT FINDINGS: Analyses of the outcomes of SCT for PID
      by specific molecular defect have clarified which conditions are receptive to
      unconditioned transplants and which require more myeloablative conditioning.
      Improved outcomes for 'difficult' conditions [adenosine deaminase-severe combined
      immunodeficiency (ADA-SCID), major histocompatibility complex class II
      deficiency] and potential advantages of using cord blood as a stem cell source
      have also been described. Newborn screening for SCID identifies well babies with
      SCID: the optimal SCT protocol for such young infants remains to be determined.
      Reduced toxicity conditioning has been successfully used to treat conditions such
      as Wiskott-Aldrich syndrome and chronic granulomatous disease, offering curative
      engraftment with reduced transplant-related mortality. Similarly, treating
      children with familial hemophagocytic lymphohistiocytosis using reduced intensity
      conditioning SCT results in much improved outcomes. Advances in next generation
      sequencing have identified new diseases amenable to SCT, such as DOCK8
      deficiency, resulting in improved quality of life and protection from malignancy.
      SUMMARY: Recent studies suggest that further improvements in treating PID with
      SCT are possible with a greater understanding of the genetics and immunobiology
      of these diseases, facilitating the matching of donor type and conditioning
      regimens, or indeed alternative therapies (such as gene therapy) to specific PID
      disorders.

PMID- 24104403
TI  - Meningococcal disease and the complement system.
AB  - Despite considerable advances in the understanding of the pathogenesis of
      meningococcal disease, this infection remains a major cause of morbidity and
      mortality globally. The role of the complement system in innate immune defenses
      against invasive meningococcal disease is well established. Individuals deficient
      in components of the alternative and terminal complement pathways are highly
      predisposed to invasive, often recurrent meningococcal infections. Genome-wide
      analysis studies also point to a central role for complement in disease
      pathogenesis. Here we review the pathophysiologic events pertinent to the
      complement system that accompany meningococcal sepsis in humans. Meningococci use
      several often redundant mechanisms to evade killing by human complement. Capsular
      polysaccharide and lipooligosaccharide glycan composition play critical roles in
      complement evasion. Some of the newly described protein vaccine antigens interact
      with complement components and have sparked considerable research interest. 

PMID- 24104409
TI  - Transplantation for myelodysplastic syndromes 2013.
AB  - PURPOSE OF REVIEW: The only current treatment capable of curing patients with
      myelodysplastic syndromes (MDS) is allogeneic haematopoietic stem cell
      transplantation (HCT). However, many MDS patients are older, often with
      substantial comorbid conditions, and the disease is heterogeneous. As a
      consequence, results of HCT vary considerably, and the practices of HCT for MDS
      are evolving. RECENT FINDINGS: The newly published modified International
      Prognostic Scoring System (IPSS-R), developed for nontransplanted patients, also
      correlates with post-HCT outcome, with the patient's karyotype having the
      strongest impact. The presence of monosomal karyotype and various genetic and
      molecular markers have also been shown to have a prognostic value. The use of
      hypomethylating agents, before or after HCT, may reduce the post-HCT relapse risk
      or delay relapse. Low and reduced-intensity conditioning regimens have allowed to
      transplant growing numbers of older patients with MDS, and the development of
      novel regimens may lead to improved relapse-free survival even in patients with
      high-risk cytogenetics. The optimal stem cell source may differ for different
      patient populations and different disease risk categories. SUMMARY: Transplant
      results for MDS have improved in recent years. Some patients even in the eighth
      decade of life have been transplanted successfully. Ongoing studies are aimed at
      further reducing transplant-related toxicity, graft-versus-host disease and post
      HCT relapse.

PMID- 24104411
TI  - Allogeneic hematopoietic cell transplantation for indolent non-Hodgkin lymphoma:
      indications and outcomes.
AB  - PURPOSE OF REVIEW: Allogeneic hematopoietic cell transplantation (HCT) can
      potentially cure indolent non-Hodgkin lymphoma (NHL). However, the optimal timing
      and indications remain unclear. Here, we review recent published reports on the
      subject and summarize our approach. RECENT FINDINGS: Recent prospective clinical
      trials of allogeneic HCT in indolent NHL are marked by substantial variation in
      eligibility criteria, patient populations, and transplant approach. Nonetheless,
      several common themes are apparent. Indolent NHL is highly susceptible to
      immunologic graft-versus-lymphoma effects and relapse rates after allogeneic HCT
      are uniformly low. Allogeneic HCT early in the disease course produces the
      highest overall and progression-free survival, but also increases patient
      exposure to potential transplant-related complications such as chronic graft
      versus-host disease. In contrast, allogeneic HCT can be reserved as a 'last
      resort' for patients who are refractory to conventional chemotherapy, delaying
      their exposure to graft-versus-host disease and other transplant-associated
      risks. No trials have directly addressed the optimal timing of allogeneic HCT in
      indolent NHL nor prospectively compared different transplant approaches. SUMMARY:
      Excellent outcomes have been reported with allogeneic HCT for indolent NHL, both
      early and late in the disease course. The optimal timing of allogeneic HCT is
      unknown and depends heavily on patient preferences.

PMID- 24104412
TI  - Haematopoietic stem cell transplantation for acquired aplastic anaemia.
AB  - PURPOSE OF REVIEW: Survival outcomes from haematopoietic stem cell
      transplantation (HSCT) in severe aplastic anaemia (SAA) have improved steadily
      over the past decades, largely reflecting progress in supportive care and
      conditioning regimens. Here we review recently published data that highlight the
      improvements and current issues. RECENT FINDINGS: Human leukocyte antigen (HLA)
      matched sibling donor (MSD) HSCT remains the gold standard for SAA patients
      younger than 40-50 years, with HLA-matched unrelated donor (MUD) HSCT for second
      line after failure to respond to immunosuppressive therapy (IST). The use of
      alternative donor sources for aplastic anaemia patients remains limited and
      problematic, but novel conditioning regimens, particularly in the haploidentical
      setting, justify further evaluation. In recent studies when comparing alemtuzumab
      based conditioning with standard antithymocyte globulin conditioning regimens,
      lower rates of acute and chronic graft-versus-host disease and better tolerance
      in older patients are seen. SUMMARY: Improving outcomes may lead to an expanded
      frontline HSCT role in the future. In children lacking a MSD, increasingly MUD
      HSCT is being considered as first-line treatment and is also being considered
      more for young adults. Further research is needed to advance our understanding of
      the role HSCT has to play in SAA with particular emphasis on alternative donor
      sources and identifying optimal conditioning regimens.

PMID- 24104413
TI  - Massive transfusion: blood component ratios.
AB  - PURPOSE OF REVIEW: This review will address recent developments in the
      transfusion management of massively transfused trauma patients, focusing on the
      use of fixed blood component ratios in massive transfusion protocols. RECENT
      FINDINGS: The majority of trauma centers have migrated from laboratory-based
      transfusion protocols to massive transfusion protocols with fixed blood component
      ratios. These protocols with red blood cell : plasma : platelet ratio of 1 : 1 :
      1 are associated with improved survival in severely injured patients. However,
      alternate ratios have also demonstrated improved survival. Thus, the optimal
      ratio has not been determined. In addition, the use of medications, such as
      antifibrinolytics, and point of care testing, such as thromboelastography, are
      increasingly being used as part of massive transfusion protocols to adjust
      transfusion therapy and decrease bleeding. However, their optimal integration has
      yet to be determined. SUMMARY: Massive transfusion protocols with fixed ratios of
      red blood cells to plasma and platelets have improved survival in both civilian
      and military trauma patients. Continued studies of ratios as well as integration
      of other therapies and testing are ongoing in order to continue to improve
      patient outcome.

PMID- 24104414
TI  - Age of blood: does older blood yield poorer outcomes?
AB  - PURPOSE OF REVIEW: Possible adverse effects of prolonged storage of red blood
      cell concentrates (RBCs) are being formally assessed both by observational
      studies and in randomized controlled trials. New mechanisms have been put forth
      to explain earlier conflicting observations. This review summarizes ongoing
      investigations into clinical and basic science studies on RBC storage effects.
      RECENT FINDINGS: Research into possible deleterious clinical effects of prolonged
      storage of RBCs has explored the contribution of various RBC production aspects
      (e.g. overnight hold, centrifugation speed, storage solution), seldom previously
      reported. Other studies investigated putative underlying mechanisms like free
      iron, inflammation, cytokines, and so on. Many publications include multiple
      analyses, like different cut-off values for 'old', or taking into account both
      oldest and average RBC storage time. Also, more studies correct for possible
      confounding effects to get a better estimate of associations. An alarming and
      ironic observation is that several studies found higher risks with fresh RBCs
      after correction for confounding. The results from the first large randomized
      controlled trials show no differences between old and fresh RBCs. SUMMARY: We
      still do not know whether older red cells have adverse effects, and if so, what
      determines such clinical effects after transfusion of 'old' RBCs. RBC production
      factors, previously seldom reported, may play an important role and should be
      reported.

PMID- 24104416
TI  - Pathogen inactivation: coming of age.
AB  - PURPOSE OF REVIEW: In the past 20 years, several pathogen inactivation
      technologies have been developed to be applied to blood components. This review
      is intended to summarize the data currently available about the technologies and
      the clinical use of products inactivated by those techniques. RECENT FINDINGS:
      Technologies for inactivating pathogens in plasma and platelets are available,
      and are increasingly used in many countries. Cumulative experience over the last
      decade in routine use supports the concept of the safety and efficacy of the
      blood components treated with pathogen inactivation technologies. SUMMARY: In
      recent years, an increase in the use of pathogen inactivation technologies for
      plasma and platelets has been observed. Their routine use in addition to
      experience generated in controlled clinical trials confirms that the treated
      blood components meet the required efficacy and safety criteria. Differences in
      epidemiology between countries, infectious risk perception, concerns about
      potential adverse effects associated with its use, and economic considerations of
      national blood systems might explain the differences observed in its
      implementation.

PMID- 24104415
TI  - Blood donor iron status: are we bleeding them dry?
AB  - PURPOSE OF REVIEW: This review examines the recent research on the prevalence,
      determinants and importance of low iron in blood donors, and on the efforts to
      reduce or prevent iron depletion in donor populations. RECENT FINDINGS: Female
      donors, especially younger women, are at highest risk for donation-induced low
      iron, but menopausal women and high-frequency donors of both sexes also face
      considerable risk for iron depletion. Predonation screening for hemoglobin
      contributes little information on donor iron status. Consumption of supplemental
      iron is helpful in preventing or reversing low iron, and waiting longer between
      donations also facilitates the recovery of the iron lost through donation.
      SUMMARY: Although the impact of phlebotomy-related iron depletion on donor health
      requires better documentation, measures are available now that can be deployed on
      a targeted or standardized basis. Blood centers, regulators, and donors should
      continue to evaluate different approaches for addressing this problem, with the
      likely outcome that no single measure is optimal for maintaining adequate
      collections while safeguarding donor health.

PMID- 24104417
TI  - Novel thrombin and factor Xa inhibitors: challenges to reversal of their
      anticoagulation effects.
AB  - PURPOSE OF REVIEW: Warfarin has been the sole oral anticoagulant used in the
      management of thromboembolic disorders for over 60 years. Target-specific oral
      anticoagulants (TSOAs) have recently emerged as alternatives to warfarin, because
      they do not require laboratory monitoring. Nevertheless, with the rising use of
      TSOAs, there is growing concern among clinicians regarding management of bleeding
      in patients taking them. Unlike warfarin, there is no antidote or reversal agent
      for TSOAs. This review summarizes recent developments and attempts to provide a
      systematic approach to patients on TSOAs presenting with bleeding complications.
      RECENT FINDINGS: Currently, data involving clinical management of TSOAs are
      limited and primarily based on ex-vivo or animal models using hemostatic agents
      with uncertain implications in bleeding patients. There is a pressing need for
      randomized clinical trials evaluating the safety and efficacy of hemostatic
      agents. SUMMARY: Without evidence-based guidelines for TSOA management,
      appropriate patient care requires an understanding of TSOA pharmacology, their
      effect on coagulation tests and, hence, a correct interpretation of test results,
      as well as a systematic approach to bleeding complications.

PMID- 24104418
TI  - Geometric light trapping with a V-trap for efficient organic solar cells.
AB  - The efficiency of today's most efficient organic solar cells is primarily limited
      by the ability of the active layer to absorb all the sunlight. While internal
      quantum efficiencies exceeding 90% are common, the external quantum efficiency
      rarely exceeds 70%. Light trapping techniques that increase the ability of a
      given active layer to absorb light are common in inorganic solar cells but have
      only been applied to organic solar cells with limited success. Here, we analyze
      the light trapping mechanism for a cell with a V-shape substrate configuration
      and demonstrate significantly improved photon absorption in an 5.3%-efficient
      PCDTBT:PC(70)BM bulk heterojunction polymer solar cell. The measured short
      circuit current density improves by 29%, in agreement with model predictions, and
      the power conversion efficiency increases to 7.2%, a 35% improvement over the
      performance in the absence of a light trap.

PMID- 24104419
TI  - Broadband absorption and efficiency enhancement of an ultra-thin silicon solar
      cell with a plasmonic fractal.
AB  - We report in this work that quantum efficiency can be significantly enhanced in
      an ultra-thin silicon solar cell coated by a fractal-like pattern of silver nano
      cuboids. When sunlight shines this solar cell, multiple antireflection bands are
      achieved mainly due to the self-similarity in the fractal-like structure.
      Actually, several kinds of optical modes exist in the structure. One is cavity
      modes, which come from Fabry-Perot resonances at the longitudinal and transverse
      cavities, respectively; the other is surface plasmon (SP) modes, which propagate
      along the silicon-silver interface. Due to the fact that several feature sizes
      distribute in a fractal-like structure, both low-index and high-index SP modes
      are simultaneously excited. As a whole effect, broadband absorption is achieved
      in this solar cell. Further by considering the ideal process that the lifetime of
      carriers is infinite and the recombination loss is ignored, we demonstrate that
      external quantum efficiency of the solar cell under this ideal condition is
      significantly enhanced. This theoretical finding contributes to high-performance
      plasmonic solar cells and can be applied to designing miniaturized compact
      photovoltaic devices. 

PMID- 24104420
TI  - Periodic dielectric structures for light-trapping in InGaAs/GaAs quantum well
      solar cells.
AB  - We study dielectric diffraction gratings for light-trapping in quantum well solar
      cells and compare their performance with plasmonic and Lambertian light-trapping
      structures. The optimum structural parameters are identified for symmetric uni
      periodic, symmetric bi-periodic and asymmetric bi-periodic gratings. The
      enhancement in short-circuit current density from the quantum well region with
      respect to a reference cell with no diffraction grating is calculated. The ratio
      of this enhancement to the maximum achievable enhancement (i.e. no transmission
      losses) is 33%, 75% and 74%, respectively for these structures. The optimum
      asymmetric and symmetric bi-periodic structures perform closest to Lambertian
      light-trapping, while all three optimum grating structures outperform optimum
      plasmonic light-trapping. We show that the short-circuit current density from the
      quantum well region is further enhanced by incorporating a rear reflector. 

PMID- 24104421
TI  - Microcavity effects on the generation, fluorescence, and diffusion of excitons in
      organic solar cells.
AB  - We compute the short-circuit diffusion current of excitons in an organic solar
      cell, with special emphasis on fluorescence losses. The exciton diffusion length
      is not uniform but varies with its position within the device, even with moderate
      fluorescence quantum efficiency. With large quantum efficiencies, the rate of
      fluorescence can be strongly reduced with proper choices of the geometrical and
      dielectric parameters. Hence, through proper micro-cavity design, the diffusion
      length can be increased and the device performance significantly improved without
      recourse to triplet excitonic states. 

PMID- 24104422
TI  - Large-size, high-uniformity, random silver nanowire networks as transparent
      electrodes for crystalline silicon wafer solar cells.
AB  - Metal nanowire networks are emerging as next generation transparent electrodes
      for photovoltaic devices. We demonstrate the application of random silver
      nanowire networks as the top electrode on crystalline silicon wafer solar cells.
      The dependence of transmittance and sheet resistance on the surface coverage is
      measured. Superior optical and electrical properties are observed due to the
      large-size, highly-uniform nature of these networks. When applying the nanowire
      networks on the solar cells with an optimized two-step annealing process, we
      achieved as large as 19% enhancement on the energy conversion efficiency. The
      detailed analysis reveals that the enhancement is mainly caused by the improved
      electrical properties of the solar cells due to the silver nanowire networks. Our
      result reveals that this technology is a promising alternative transparent
      electrode technology for crystalline silicon wafer solar cells. 

PMID- 24104423
TI  - Light harvesting enhancement in solar cells with quasicrystalline plasmonic
      structures.
AB  - Solar cells are important in the area of renewable energies. Since it is
      expensive to produce solar-grade silicon [Electrochem. Soc. Interface 17, 30
      (2008)], especially thin-film solar cells are interesting. However, the
      efficiency of such solar cells is low. Therefore, it is important to increase the
      efficiency. The group of Polman has shown that a periodic arrangement of metal
      particles is able to enhance the absorbance of light [Nano Lett. 11, 1760
      (2011)]. However, a quasicrystalline arrangement of the metal particles is
      expected to enhance the light absorbance independent of the incident polar and
      azimuthal angles due to the more isotropic photonic bandstructure. In this paper,
      we compare the absorption enhancement of a quasiperiodic photonic crystal to that
      of a periodic photonic crystal. We indeed find that the absorption enhancement
      for the quasicrystalline arrangement shows such an isotropic behavior. This
      implies that the absorption efficiency of the solar cell is relatively constant
      during the course of the day as well as the year. This is particularly important
      with respect to power distribution, power storage requirements, and the stability
      of the electric grid upon massive use of renewable energy. 

PMID- 24104424
TI  - Multi-resonant absorption in ultra-thin silicon solar cells with metallic
      nanowires.
AB  - We propose a design to confine light absorption in flat and ultra-thin amorphous
      silicon solar cells with a one-dimensional silver grating embedded in the front
      window of the cell. We show numerically that multi-resonant light trapping is
      achieved in both TE and TM polarizations. Each resonance is analyzed in detail
      and modeled by Fabry-Perot resonances or guided modes via grating coupling. This
      approach is generalized to a complete amorphous silicon solar cell, with the
      additional degrees of freedom provided by the buffer layers. These results could
      guide the design of resonant structures for optimized ultra-thin solar cells. 

PMID- 24104425
TI  - Enhanced efficiency of thin film solar cells using a shifted dual grating
      plasmonic structure.
AB  - We propose an ultrathin solar cell architecture design which incorporates two
      periodic layers of metallic and dielectric gratings. Both layers couple the
      incident light to photonic and plasmonic modes, thus increasing absorption within
      the cell. The relative position between the two gratings is examined, and is
      shown to have significant impact on absorption. A lateral shift between the two
      layers introduces structural asymmetry, and enables coupling of the incident
      field to optically dark photonic modes. Furthermore, the lateral shift influences
      mode interactions. Current density enhancement is calculated under AM1.5 G solar
      illumination, and is found to reach a value of 1.86. The structure proposed is
      optimized and compared to solar cells with a single layer of metallic or
      dielectric nanostructures.

PMID- 24104426
TI  - FDTD modeling of solar energy absorption in silicon branched nanowires.
AB  - Thin film nanostructured photovoltaic cells are increasing in efficiency and
      decreasing the cost of solar energy. FDTD modeling of branched nanowire 'forests'
      are shown to have improved optical absorption in the visible and near-IR spectra
      over nanowire arrays alone, with a factor of 5 enhancement available at 1000 nm.
      Alternate BNW tree configurations are presented, achieving a maximum absorption
      of over 95% at 500 nm. 

PMID- 24104427
TI  - Tailored free-form optics with movement to integrate tracking in concentrating
      photovoltaics.
AB  - The economic use of high-efficiency solar cells in photovoltaics requires high
      concentration of sunlight and therefore precise dual-axis tracking of the sun.
      Due to their size and bulkiness, these trackers are less adequate for small- to
      mid-scale installations like flat rooftops. Our approach to combine concentrating
      and tracking of sunlight utilizes two laterally moving lens arrays. The presented
      analytic optics design method allows direct calculation of the free-form lens
      surfaces while incorporating the lateral movement. The obtained concentration
      performance exceeds a factor of 500. This demonstrates that one can benefit from
      high-efficiency solar cells and more compact and flexible single-axis trackers at
      the same time. 

PMID- 24104428
TI  - Conversion efficiency of broad-band rectennas for solar energy harvesting
      applications.
AB  - Optical antennas have been proposed as an alternative option for solar energy
      harvesting. In this work the power conversion efficiency of broadband antennas,
      log-periodic, square-spiral, and archimedian-spiral antennas, coupled to Metal
      Insulator-Metal and Esaki rectifying diodes has been obtained from both
      theoretical and numerical simulation perspectives. The results show efficiencies
      in the order of 10(-6) to 10(-9) for these rectifying mechanisms, which is very
      low for practical solar energy harvesting applications. This is mainly caused by
      the poor performance of diodes at the given frequencies and also due to the
      antenna-diode impedance mismatch. If only losses due to antenna-diode impedance
      mismatch are considered an efficiency of about 10(-3) would be obtained. In order
      to make optical antennas useful for solar energy harvesting new rectification
      devices or a different harvesting mechanism should be used.

PMID- 24104429
TI  - The role of propagating modes in silver nanowire arrays for transparent
      electrodes.
AB  - Silver nanowires have been shown to demonstrate enhanced transmission and
      promising potential for next-generation transparent electrodes. In this paper, we
      systematically investigated the electrical and optical properties of 1D and 2D
      silver nanowire arrays as a function of diameter and pitch and compared their
      performance to that of silver thin films. Silver nanowires were found to exhibit
      enhanced transmission over thin films due to propagating resonance modes between
      nanowires. We evaluated the angular dependence and dispersion relation of these
      propagating modes and demonstrate that larger nanowire diameters and pitches are
      favored for achieving higher solar transmission at a particular sheet resistance.
      Silver nanowires may achieve achieve solar transmission > 90% with sheet
      resistances of a few Omega/sq and figure of merit sigmadc/sigmaop > 1000. 

PMID- 24104430
TI  - Focus issue introduction: renewable energy and the environment.
AB  - This focus issue highlights selected contributions from authors who presented
      promising concepts at OSA's Renewable Energy and the Environment Optics and
      Photonics Congress held 11-15 November 2012 in Eindhoven, The Netherlands. 

PMID- 24104431
TI  - Dual gratings for enhanced light trapping in thin-film solar cells by a layer
      transfer technique.
AB  - Thin film solar cells benefit significantly from the enhanced light trapping
      offered by photonic nanostructures. The thin film is typically patterned on one
      side only due to technological constraints. The ability to independently pattern
      both sides of the thin film increases the degrees of freedom available to the
      designer, as different functions can be combined, such as the reduction of
      surface reflection and the excitation of quasiguided modes for enhanced light
      absorption. Here, we demonstrate a technique based on simple layer transfer that
      allows us to independently pattern both sides of the thin film leading to
      enhanced light trapping. We used a 400 nm thin film of amorphous hydrogenated
      silicon and two simple 2D gratings for this proof-of-principle demonstration.
      Since the technique imposes no restrictions on the design parameters, any type of
      structure can be made. 

PMID- 24104432
TI  - The impact of the non-linearity of the radiant flux on the thermal load of the
      color conversion elements in phosphor converted LEDs under different current
      driving schemes.
AB  - For a systematic approach to improve the reliability and the white light quality
      of phosphor converted light-emitting diodes (LEDs) it is imperative to gain a
      better understanding of the individual parameters that affect color temperature
      constancy and maintenance. By means of a combined optical and thermal simulation
      procedure, in this contribution we give a comprehensive discussion on the impact
      of different current driving schemes on the thermal load of the color conversion
      elements (CCEs) of phosphor converted LEDs. We show that on the one hand a
      decreasing duty cycle under pulse width modulation driving conditions may cause a
      notable temperature variation and on the other hand also effects due to the non
      linearity between the blue radiant flux and the current have to be considered for
      the thermal load of the CCEs. 

PMID- 24104433
TI  - Combining randomly textured surfaces and photonic crystals for the photon
      management in thin film microcrystalline silicon solar cells.
AB  - Photon management aims at optimizing the solar cell efficiency by, e.g.,
      incorporating supporting optical nanostructures for absorption enhancement. Their
      geometrical design, however, is usually a compromise since requirements in
      different spectral domains need to be accommodated. This issue can be mitigated
      if multiple optical nanostructures are integrated. Here, we present a photon
      management scheme that combines the benefits of a randomly textured surface and
      an opaline photonic crystal. Moreover, upon considering the device with an
      increasing complexity, we show that a structure that respects the mutual
      fabrication constraints has the best performance, i.e., a device where the
      photonic crystal is not perfect but to some extent amorphous as enforced by the
      presence of the texture. 

PMID- 24104434
TI  - Disordered photonic structures for light harvesting in solar cells.
AB  - The effect of periodic and disordered photonic structures on the absorption
      efficiency of amorphous and crystalline Silicon thin-film solar cells is
      investigated numerically. We show that disordered patterns possessing a short
      range correlation in the position of the holes yield comparable, or even
      superior, absorption enhancements than periodic (photonic crystal) patterns. This
      work provides clear evidence that non-deterministic photonic structures represent
      a viable alternative strategy for photon management in thin-film solar cells,
      thereby opening the route towards more efficient and potentially cheaper
      photovoltaic technologies. 

PMID- 24104435
TI  - Effect of polymer morphology on P3HT-based solid-state dye sensitized solar
      cells: an ultrafast spectroscopic investigation.
AB  - Solid-state dye sensitized solar cell devices are fabricated with poly(3
      hexylthiophene) (P3HT) as the hole transporting layer. Upon annealing treatment
      we obtained ~ 70% increase in the device efficiency compared to un-annealed
      devices. Our investigation, by means of ultrafast transient absorption
      spectroscopic characterization, correlates the increased device performances to a
      more efficient hole-transfer at the dye/polymer interface in the thermally
      treated P3HT.

PMID- 24104436
TI  - Nitride micro-LEDs and beyond--a decade progress review.
AB  - Since their inception, micro-size light emitting diode (uLED) arrays based on III
      nitride semiconductors have emerged as a promising technology for a range of
      applications. This paper provides an overview on a decade progresses on realizing
      III-nitride uLED based high voltage single-chip AC/DC-LEDs without power
      converters to address the key compatibility issue between LEDs and AC power grid
      infrastructure; and high-resolution solid-state self-emissive microdisplays
      operating in an active driving scheme to address the need of high brightness,
      efficiency and robustness of microdisplays. These devices utilize the photonic
      integration approach by integrating uLED arrays on-chip. Other applications of
      nitride uLED arrays are also discussed. 

PMID- 24104437
TI  - Anisotropic light emissions in luminescent solar concentrators-isotropic systems.
AB  - In this paper we develop a model to describe the emission profile from randomly
      oriented dichroic dye molecules in a luminescent solar concentrator (LSC)
      waveguide as a function of incoming light direction. The resulting emission is
      non-isotropic, in contradiction to what is used in almost all previous
      simulations on the performance of LSCs, and helps explain the large surface
      losses measured in these devices. To achieve more precise LSC performance
      simulations we suggest that the dichroic nature of the dyes must be included in
      the future modeling efforts. 

PMID- 24104438
TI  - Free-form optics for Fresnel-lens-based photovoltaic concentrators.
AB  - The Concentrated Photovoltaics (CPV) promise relies upon the use of high
      efficiency triple-junction solar cells (with proven efficiencies of over 44%) and
      upon high-performance optics that allow for high concentration concurrent with
      relaxed manufacturing tolerances (all key elements for low-cost mass production).
      Additionally, uniform illumination is highly desirable for efficiency and
      reliability reasons. All of these features have to be achieved with inexpensive
      optics containing only a few (in general no more than 2) optical elements. In
      this paper we show that the degrees of freedom using free-forms allow the
      introduction of multiple functionalities required for CPV with just 2 optical
      elements, one of which is a Fresnel lens. 

PMID- 24104439
TI  - Luminescent solar concentrators with fiber geometry.
AB  - The potential of a fibre luminescent solar concentrator has been explored by
      means of both analytical and ray-tracing techniques. Coated fibres have been
      found to be more efficient than homogeneously doped fibres, at low absorption.
      For practical fibres concentration is predicted to be linear with fibre length. A
      1 m long, radius 1 mm, fibre LSC doped with Lumogen Red 305 is predicted to
      concentrate the AM1.5 g spectrum up to 1100 nm at normal incidence by ~35 x. The
      collection efficiency under diffuse and direct irradiance in London has been
      analysed showing that, even under clear sky conditions, in winter the diffuse
      contribution equals the direct.

PMID- 24104440
TI  - Photonic crystals and optical mode engineering for thin film photovoltaics.
AB  - In this paper, we present the design, analysis, and experimental results on the
      integration of 2D photonic crystals in thin film photovoltaic solar cells based
      on hydrogenated amorphous silicon. We introduce an analytical approach based on
      time domain coupled mode theory to investigate the impact of the photon lifetime
      and anisotropy of the optical resonances on the absorption efficiency. Specific
      design rules are derived from this analysis. We also show that, due to the
      specific properties of the photonic crystal resonances, the angular acceptance of
      such solar cells is particularly high. Rigorous Coupled Wave Analysis simulations
      show that the absorption in the a-Si:H active layers, integrated from 300 to 750
      nm, is only decreased from 65.7% to 60% while the incidence angle is increased
      from 0 to 55 degrees . Experimental results confirm the stability of the incident
      light absorption in the patterned stack, for angles of incidence up to 50 degrees
      .

PMID- 24104441
TI  - Automated spray coating process for the fabrication of large-area artificial
      opals on textured substrates.
AB  - 3D photonic crystals, such as opals, have been shown to have a high potential to
      increase the efficiency of solar cells by enabling advanced light management
      concepts. However, methods which comply with the demands of the photovoltaic
      industry for integration of these structures, i. e. the fabrication in a low
      cost, fast, and large-scale manner, are missing up to now. In this work, we
      present the spray coating of a colloidal suspension on textured substrates and
      subsequent drying. We fabricated opaline films of much larger lateral dimensions
      and in much shorter times than what is possible using conventional opal
      fabrication methods. 

PMID- 24104442
TI  - Enhanced light absorption in thin-film solar cells with light propagation
      direction conversion.
AB  - Enhancement of optical absorption in thin-film solar cells (TF-SCs) has been the
      long-lasting issue to achieve high efficiencies. Grating couplers have been
      studied for the conversion of incident light into guided modes propagating along
      TF-SCs to extend optical path for higher optical absorption. However the
      wavelength band for the efficient conversion remained relatively narrow and the
      overall improvement of TF-SC efficiencies has been limited. This paper
      demonstrates that the grating height design as well as the phase matching
      condition is important for the enhancement of optical absorption in TF-SCs with
      the calculation of short-circuit currents as a figure of merit for optimization.
      The influence of the light absorption coefficients and grating coupling strengths
      on the light absorption bandwidth is also discussed. 

PMID- 24104443
TI  - Misaligned conformal gratings enhanced light trapping in thin film silicon solar
      cells.
AB  - The effect of the relative lateral displacement between the front and back
      sinusoidal textured layers of a conformal grating solar cell on light trapping
      was investigated. For various amount of relative lateral displacements and
      thicknesses of the active layer, the external quantum efficiency (EQE) of the
      misaligned solar cell structures and their EQE enhancement relative to the
      aligned structure were studied. For both aligned and misaligned solar cell
      structures, the electric field distribution at the wavelength corresponding to
      the EQE peaks was analyzed, and the corresponding guided modes were identified.
      Additional modes were observed in the misaligned grating structures. A 25.1 times
      enhancement of the EQE at the wavelength of 950 nm and an average of 2.2 times
      enhancement in the wavelength range from 700 to 900 nm were observed. For the
      misaligned grating structure with the phase shift beta = pi/4 and the active
      layer thickness D(Si) = 230 nm, a maximum short circuit current density J(sc)
      enhancement of 34% was achieved for normal incidence, and a short circuit current
      enhancement of more than 15% was obtained for the incident angle between -15
      degrees  and + 15 degrees .

PMID- 24104444
TI  - Efficient light management in vertical nanowire arrays for photovoltaics.
AB  - Vertical arrays of direct band gap III-V semiconductor nanowires (NWs) hold the
      prospect of cheap and efficient next-generation photovoltaics, and guidelines for
      successful light-management are needed. Here, we use InP NWs as a model system
      and find, through electrodynamic modeling, general design principles for
      efficient absorption of sun light in nanowire arrays by systematically varying
      the nanowire diameter, the nanowire length, and the array period. Most
      importantly, we discover the existence of specific band-gap dependent diameters,
      170 nm and 410 nm for InP, for which the absorption of sun light in the array is
      optimal, irrespective of the nanowire length. At these diameters, the individual
      InP NWs of the array absorb light strongly for photon energies just above the
      band gap energy due to a diameter-tunable nanophotonic resonance, which shows up
      also for other semiconductor materials of the NWs. Furthermore, we find that for
      maximized absorption of sun light, the optimal period of the array increases with
      nanowire length, since this decreases the insertion reflection losses. 

PMID- 24104445
TI  - Pre-fractal multilayer structure for polarization- insensitive temporally and
      spatially coherent thermal emitter.
AB  - We investigate electromagnetic wave propagation through one-dimensional stacks
      arranged as truncated pre-fractal Cantor multilayer. Taking into account
      materials' dispersion as well as real absorptive losses, we studied the spectral
      and spatial emissivity in both on-axis and off-axis direction. The typical cavity
      mode resonances associated to the pre-fractal structure are exploited to design a
      polarization-insensitive infrared emitter pertaining both temporal and spatial
      coherence. 

PMID- 24104446
TI  - Differences in muscle activation patterns during step recovery in elderly women
      with and without a history of falls.
AB  - BACKGROUND AND AIMS: This study aimed at comparing the patterns of muscle
      activation used in stepping to regain balance during a forward fall between
      subjects with and without a history of falling and at identifying the causes of
      functional deficits in recovery stepping. METHODS: Elderly women with and without
      a history of falling (fallers: n = 12, mean age +/- SD = 82.8 +/- 4.5 years; non
      fallers: n = 17, age = 81.4 +/- 3.4 years) participated in the study. The
      subjects were suspended in a forward-leaning position by a lean-control cable
      with a load of 15 % of body weight and instructed to regain standing balance upon
      release by taking a single step forward. Electromyography (EMG) data were
      obtained from five lower extremity muscles on the stepping side, and the muscle
      activation patterns were compared between fallers and non-fallers. RESULTS:
      Fallers had a shorter step length and slower step velocity than non-fallers. The
      EMG time-to-peak for the gastrocnemius muscle, which provides push-off prior to
      foot lift-off, was slower for fallers than for non-fallers, whereas the EMG onset
      times of the biceps femoris and gastrocnemius muscles were similar between the
      groups. The fallers exhibited significantly delayed muscle deactivation of the
      upper leg and increased co-contraction between the rectus femoris and biceps
      femoris during the stepping phase than did the non-fallers. CONCLUSIONS: These
      findings suggest that the muscle activation pattern during the regain balance may
      reflect an inability to step forward rapidly in elderly women with a history of
      falls.

PMID- 24104447
TI  - Antitumor activity of the beta-glucan paramylon from Euglena against
      preneoplastic colonic aberrant crypt foci in mice.
AB  - In the present study, the effects of beta-glucans isolated from Euglena on the
      formation of preneoplastic aberrant crypt foci (ACF) in the colon were examined
      in mice. Mice were fed a semi-purified AIN-93M diet containing cellulose or the
      same diet but with the cellulose replaced with beta-glucans in the form of
      Euglena, paramylon, or amorphous paramylon, for 11 weeks. After consuming these
      dietary supplements for 8 days, half of the mice were intraperitoneally
      administered 1,2-dimethylhydrazine (DMH) at a dose of 20 mg kg(-1) body weight
      every week for 6 weeks. Among the DMH-treated groups, the paramylon- and
      amorphous paramylon-fed mice displayed a significantly lower number of ACF than
      the control group. Also, the liver weight of the paramylon group was markedly
      decreased compared with those of the control and Euglena groups, whereas the
      cecal content weight and fecal volume of the paramylon group were significantly
      increased. As for the levels of organic acids in the cecal contents, the
      paramylon group displayed significantly increased lactic acid levels compared
      with the control and Euglena groups. From these findings, although the mechanism
      of the ACF-inhibiting effects of paramylon remains unclear, it is considered that
      beta-glucans, such as paramylon and its isomer amorphous paramylon, have
      preventive effects against colon cancer and are more effective against the
      condition than Euglena. 

PMID- 24104448
TI  - Sensitivity and feasibility of lung ultrasound in bronchiolitis -- reply to the
      correspondence letter by Catalano.

PMID- 24104449
TI  - X-ray image enhancement via determinant based feature selection.
AB  - Previous work has investigated the feasibility of using Eigenimage-based
      enhancement tools to highlight abnormalities on chest X-rays (Butler et al in J
      Med Imaging Radiat Oncol 52:244-253, 2008). While promising, this approach has
      been limited by computational restrictions of standard clinical workstations, and
      uncertainty regarding what constitutes an adequate sample size. This paper
      suggests an alternative mathematical model to the above referenced singular value
      decomposition method, which can significantly reduce both the required sample
      size and the time needed to perform analysis. Using this approach images can be
      efficiently separated into normal and abnormal parts, with the potential for
      rapid highlighting of pathology. 

PMID- 24104450
TI  - Orientational variation, solvate composition and molecular flexibility in well
      ordered cocrystals of the fullerene C70 with
      bis(ethylenedithio)tetrathiafulvalene.
AB  - Cocrystallization of C70 with bis(ethylenedithio)tetrathiafulvalene (ET) produces
      two different solvates, C70.ET.C6H6 and 2C70.2ET.CS2, which show distinctly
      different overlap between the fullerene and ET molecules. 

PMID- 24104451
TI  - Thrombospondin-1-induced smooth muscle cell chemotaxis and proliferation are
      dependent on transforming growth factor-beta2 and hyaluronic acid synthase.
AB  - Angioplasty causes local vascular injury, leading to the release of
      thrombospondin-1 (TSP-1), which stimulates vascular smooth muscle cell (VSMC)
      migration and proliferation, important steps in the development of intimal
      hyperplasia. Transforming growth factor beta 2 (TGF-beta2) and hyaluronic acid
      synthase (HAS) are two pro-stenotic genes upregulated in VSMCs by TSP-1. We
      hypothesized that inhibition of TGF-beta2 or HAS would inhibit TSP-1-induced VSMC
      migration, proliferation, and TSP-1 signaling. Our data demonstrate that
      Inhibition of either TGF-beta2 or HAS inhibited TSP-1-induced VSMC migration and
      proliferation. Activation of ERK 1 was decreased by TGF-beta2 inhibition and
      unaffected by HAS inhibition. TGF-beta2 and HAS are not implicated in TSP-1
      induced thbs1 expression, while they are each implicated in TSP-1-induced
      expression of their own gene. In summary, TSP-1-induced VSMC migration and
      proliferation rely on intact TGF-beta2 signaling and HAS function. TSP-1
      activation of ERK 1 is dependent on TGF-beta2. These data further expand our
      understanding of the complexity of TSP-1 cellular signaling and the involvement
      of TGF-beta2 and HAS. 

PMID- 24104452
TI  - Inhibition of autophagy enhances apoptosis induced by proteasome inhibitor
      bortezomib in human glioblastoma U87 and U251 cells.
AB  - Glioblastoma is the most aggressive cerebral gliomas. Despite advances in
      therapies, the prognosis is still very poor. Therefore, novel therapeutic
      strategies are required. As a proteasome inhibitor, bortezomib has shown its
      efficacy as an active antitumor agent against a variety of tumors. However,
      inhibition of proteasome activity leads to cell death and also induces cell
      autophagy, and due to the dual roles of autophagy in the survival and death of
      tumor cells, the effect of inhibition of autophagy on glioblastoma cells remains
      to be explored. We therefore assessed whether bortezomib is capable of inducing
      autophagy, and investigated the antitumor effect of bortezomib combined with
      autophagy inhibitors on human glioblastoma U251 and U87 cells. Cell viability was
      measured by MTT assay. The expressions of autophagy and apoptosis-related
      proteins were determined by Western blot analysis. U251 and U87 cells
      proliferation was inhibited in a dose-dependent manner. Both apoptosis and
      autophagy induced by bortezomib were observed in human glioblastoma U87 and U251
      cells. However, when U251 and U87 cells were co-treated with bortezomib and
      autophagy inhibitors 3-MA or Atg7 siRNA, the autophagy inhibitors blocked the
      autophagy in the cells and resulted in a further inhibition of cell proliferation
      and a further increase in cell apoptosis as compared with that treated with
      bortezomib alone. These findings indicated that combination of bortezomib and
      autophagy inhibitors may shed new light on glioblastoma treatment.

PMID- 24104453
TI  - Human umbilical cord mesenchymal stem cells inhibit C6 glioma growth via
      secretion of dickkopf-1 (DKK1).
AB  - Mesenchymal stem cells (MSCs) represent a potential therapeutic target for
      glioma. We determined the molecular mechanism of inhibitory effect of human
      umbilical cord-derived MSCs (hUC-MSCs) on the growth of C6 glioma cells. We
      demonstrated that hUC-MSCs inhibited C6 cell growth and modulated the cell cycle
      to G0/G1 phase. The expression of beta-catenin and c-Myc was downregulated in C6
      cells by conditioned media from hUC-MSCs, and the levels of secreted DKK1 were
      positively correlated with concentrations of hUCMSCs-CM. The inhibitory effect of
      hUC-MSCs on C6 cell proliferation was enhanced as the concentration of DKK1 in
      hUCMSCs-CM increased. When DKK1 was neutralized by anti-DKK1 antibody, the
      inhibitory effect of hUC-MSCs on C6 cells was attenuated. Furthermore, we found
      that conditioned media from hUC-MSCs transfection with siRNA targeting DKK1 mRNA
      or pEGFPN1-DKK1 plasmid lost or enhanced the abilities to regulate the Wnt
      signaling in C6 cells. Therefore, hUC-MSCs inhibited C6 glioma cell growth via
      secreting DKK1, an inhibitor of Wnt pathway, may represent a novel therapeutic
      strategy for malignant glioma.

PMID- 24104454
TI  - Functional role and analysis of cysteine residues of the salt tolerance protein
      Sod2.
AB  - Sod2 is the major salt tolerance plasma membrane protein of Schizosaccharomyces
      pombe. It functions to remove excess intracellular sodium (or lithium) in
      exchange for protons. We investigated the role of cysteine residues and created a
      cysteine-free Sod2 protein. Each cysteine residue of the ten present was
      individually mutated to serine and the different proteins expressed and
      characterized in S. pombe. Western blotting revealed that all the individual
      mutant proteins were expressed. We examined the ability of the mutant proteins to
      confer salt tolerance to S. pombe with the endogenous Sod2 protein deleted. Only
      proteins with C26S and C374S mutations were partially reduced in their ability to
      confer salt tolerance. Additionally, they showed a change in conformation in
      comparison to the wild-type protein, indicated by differential sensitivity to
      trypsin. Deletion of all the cysteine residues of Sod2 resulted in a functional
      protein that was expressed in S. pombe at levels similar to the wild type and
      also conferred salt tolerance. The conformation of the cysteine-free Sod2 protein
      was not altered relative to the wild-type protein. We examined the accessibility
      of amino acids of the cysteineless protein present on putative extracellular loop
      2. A cysteine placed at position Ala119 was accessible to externally applied [2
      (trimethylammonium)ethyl] methane thiosulfonate bromide. The results demonstrate
      that cysteines in the Sod2 protein can be changed to serine residues resulting in
      an expressed, functional protein. The utility of the cysteine-free Sod2 protein
      for determination of topology and amino acid accessibility is demonstrated. 

PMID- 24104455
TI  - A comparative study of glycoproteomes in androgen-sensitive and -independent
      prostate cancer cell lines.
AB  - Prostate cancer is one of the most common malignancies in men and is predicted to
      be the second leading cause of cancer-related deaths. After 6-18 months, hormone
      ablation treatment results in androgen-independent growth of cancer cells,
      metastasis and progression. The mechanism of androgen-independent growth of
      prostatic carcinoma cells is still unknown. Identification of factors that
      facilitate the transition from androgen-dependent to independent states is
      crucial in designing future diagnostics and medication strategies. To understand
      the biochemical meaning of hormone dependency deprivation, glycoproteins enriched
      profiles were compared between DU145 (hormone non-responding) and LNCaP (hormone
      responding) prostate cancer cells. These results allow for anticipation on the
      important role of glycosylation in malignant transformation. Both Tn antigen and
      complex antennary N-oligosaccharides were recognized. Their occurrence might be
      involved in the development and progression of tumor, and failure of hormone
      ablation therapy. Among identified proteins in androgen-sensitive cells nucleolin
      (P19338) was found that is widely described as apoptosis inhibitor, and also
      transporter of molecules from the membrane to the cytoplasm or nucleus. In
      addition, 14-3-3 protein family (P27348, P31946, P61981, P63104, P62258, Q04917,
      and P31947) was investigated across available databases as it forms stable
      complexes with glycoproteins. Our studies indicate that isoforms: sigma and eta
      were found in androgen-dependent prostate cancer cells, while other isoforms were
      present in androgen non-responding cells. 14-3-3 binding partners are involved in
      cancer pathogenesis. These findings may contribute to a better understanding of
      prostate cancer tumorigenesis and to a more efficient prognosis and individual
      therapy in a future. However, it still remains to be revealed how important those
      changes are for androgen dependency loss in prostate cancer patients carried out
      on clinically relevant populations. 

PMID- 24104456
TI  - Probing protein ensemble rigidity and hydrogen-deuterium exchange.
AB  - Protein rigidity and flexibility can be analyzed accurately and efficiently using
      the program floppy inclusion and rigid substructure topography (FIRST). Previous
      studies using FIRST were designed to analyze the rigidity and flexibility of
      proteins using a single static (snapshot) structure. It is however well known
      that proteins can undergo spontaneous sub-molecular unfolding and refolding, or
      conformational dynamics, even under conditions that strongly favor a well-defined
      native structure. These (local) unfolding events result in a large number of
      conformers that differ from each other very slightly. In this context, proteins
      are better represented as a thermodynamic ensemble of 'native-like' structures,
      and not just as a single static low-energy structure. Working with this notion,
      we introduce a novel FIRST-based approach for predicting rigidity/flexibility of
      the protein ensemble by (i) averaging the hydrogen bonding strengths from the
      entire ensemble and (ii) by refining the mathematical model of hydrogen bonds.
      Furthermore, we combine our FIRST-ensemble rigidity predictions with the ensemble
      solvent accessibility data of the backbone amides and propose a novel
      computational method which uses both rigidity and solvent accessibility for
      predicting hydrogen-deuterium exchange (HDX). To validate our predictions, we
      report a novel site specific HDX experiment which characterizes the native
      structural ensemble of Acylphosphatase from hyperthermophile Sulfolobus
      solfataricus (Sso AcP). The sub-structural conformational dynamics that is
      observed by HDX data, is closely matched with the FIRST-ensemble rigidity
      predictions, which could not be attained using the traditional single 'snapshot'
      rigidity analysis. Moreover, the computational predictions of regions that are
      protected from HDX and those that undergo exchange are in very good agreement
      with the experimental HDX profile of Sso AcP. 

PMID- 24104457
TI  - Role of type 1 natural killer T cells in pulmonary immunity.
AB  - Mucosal sites are populated by a multitude of innate lymphoid cells and "innate
      like" T lymphocytes expressing semiconserved T-cell receptors. Among the latter
      group, interest in type I natural killer T (NKT) cells has gained considerable
      momentum over the last decade. Exposure to NKT cell antigens is likely to occur
      continuously at mucosal sites. For this reason, and as they rapidly respond to
      stress-induced environmental cytokines, NKT cells are important contributors to
      immune and inflammatory responses. Here, we review the dual role of mucosal NKT
      cells during immune responses and pathologies with a particular focus on the
      lungs. Their role during pulmonary acute and chronic inflammation and respiratory
      infections is outlined. Whether NKT cells might provide a future attractive
      therapeutic target for treating human respiratory diseases is discussed. 

PMID- 24104459
TI  - Obstructive sleep apnea, atrial fibrillation, and erectile dysfunction: are they
      only coexisting conditions or a new clinical syndrome? The concept of the OSAFED
      syndrome.
AB  - Patients rarely suffer from only 1 disease. Most of them have several conditions
      with common risk factors and etiology, and which often increase the severity of
      each other. The phenotypes linked to 1 condition are often linked to many others.
      We describe 3 patients with obstructive sleep apnea (OSA), atrial fibrillation
      (AF), and erectile dysfunction (ED), all of which are highly prevalent in the
      general population. OSA is one of the most common sleep disorders, affecting
      approximately 24% of men and 9% of women between 30 and 60 years of age. AF is
      one of the most common arrhythmias, present in approximately 2% of the
      population, and erectile dysfunction can be found in 18% to 40% of the male
      population older than 20 years. The presence of these 3 conditions in the same
      patient may be not only a coincidence but rather a new clinical syndrome. We
      present data which allow one to consider OSA, AF, and ED as parts of a clinical
      syndrome: OSAFED (obstructive sleep apnea, atrial fibrillation, and erectile
      dysfunction), with a larger effect on the cardiovascular risk profile than those
      3 conditions taken alone. Introducing the OSAFED acronym into everyday clinical
      practice would have the tremendous advantage of reminding health care workers to
      screen every patient with either OSA, AF, or ED for the remaining 2 diseases.
      This would result in an early diagnosis and break the vicious circle of mutual
      disease exacerbation. 

PMID- 24104460
TI  - Half-dose recombinant tissue plasminogen activator treatment in venous
      thromboembolism.
AB  - INTRODUCTION: Pulmonary embolism (VTE) comes in different degrees of severity
      from massive pulmonary embolism to nonmassive pulmonary embolism with no symptoms
      or hypoxia. Thrombolytic therapy is a lifesaver especially for patients who are
      in the high-risk group. In this study, we aimed at evaluating symptoms and
      clinical and laboratory findings in patients who had a diagnosis of massive or
      submassive VTE and treated with 50-mg recombinant tissue plasminogen activator
      (rt-PA) per hour for various problems as opposed to the standard dose, which is
      100 mg every 2 hours. MATERIALS AND METHODS: Forty-six patients with a diagnosis
      of massive or submassive VTE who received thrombolytic therapy were evaluated
      retrospectively. Twenty-three patients who were treated with 50-mg rt-PA per hour
      were included in the study group. On the other hand, 23 patients who were treated
      with 100 mg of intravenous infusion of rt-PA every 2 hours were included in the
      control group. Echocardiographic assessment of the right ventricular size,
      systolic pulmonary artery pressure (sPAP), oxygen saturation, systemic arterial
      pressure, and heart rate before the thrombolytic therapy and in the first 24
      hours after the administration of therapy were checked and noted in both of the
      groups. RESULTS: No significant difference was found between the 2 groups with
      regard to demographic data, Wells scores, type of embolism, average symptom
      duration, sPAP, and oxygen saturation. Differences in recovery, as inferred from
      vital symptoms and sPAP measurements, were not significant between the 2 groups.
      CONCLUSIONS: Lower-dose thrombolytic therapy showed similar efficacy versus the
      standard dose in VTE. Thrombolytic therapy is a life-saving treatment in massive
      VTE. Furthermore, a harm/benefit analysis may lead to the administration of half
      dose therapy in selected cases when it is contraindicated for various reasons.

PMID- 24104458
TI  - Characterizing CEACAM5 interaction with CD8alpha and CD1d in intestinal
      homeostasis.
AB  - Normal intestinal epithelial cells (IECs) could act as non-professional antigen
      presenting cells, selectively activating CD8(+)-suppressor T cells. An epithelial
      cell surface glycoprotein, gp180, recognized by monoclonal antibodies B9 and L12
      was determined to be critical in this process. Purification and sequence analysis
      of mAb B9 reactive material revealed amino-acid sequence homology with CEACAM5.
      We demonstrate that CEACAM5 has properties attributed to gp180, such as CD8alpha
      binding and activation of CD8-associated Lck. CEACAM5 is the only CEACAM member
      interacting with CD1d through the B3 domain. Its N domain (recognized by B9) is
      required for CD8alpha binding. Removal of the N-domain glycosylated residues
      reduces B9 recognition, CD8alpha binding affinity, and activation of LcK.
      Therefore, conformational changes in CEACAM5 glycosylation site are critical for
      its interaction with CD8alpha. CEACAM5-activated CD8(+) T cells acquire the
      ability to suppress the proliferation of CD4(+) T cells in vitro in the presence
      of interleukin (IL)-15 or IL-7. We provide new insights into the role of CEACAM5
      and define its specific immunoregulatory properties among the CEACAMs expressed
      on IECs. We suggest that unique set of interactions between CEACAM5, CD1d, and
      CD8 render CD1d more class I-like molecule, facilitating antigen presentation and
      activation of CD8(+)-suppressor regulatory T cells. 

PMID- 24104462
TI  - Physiological responses to the Glittre-ADL test in patients with chronic
      obstructive pulmonary disease.
AB  - OBJECTIVE: The aim of this study was to investigate the physiological responses
      induced by the Glittre-ADL test (TGlittre) test in patients with chronic
      obstructive pulmonary disease (COPD) and compare them with those induced by the 6
      minute walk test (6MWT). DESIGN: Cross-sectional observational study. SUBJECTS:
      Eighteen patients with COPD 66 years (standard deviation (SD) 8) and forced
      expiratory volume in 1 s of 40.4% (SD 16.8) predicted) who performed in
      randomized order the 6MWT and TGlittre on 2 separate days. RESULTS: Baseline
      cardiopulmonary variables were similar between the 6MWT and TGlittre (p > 0.05).
      TGlittre induced slightly higher final VO2 than 6MWT 83.6 ml/min (SD 163.9); p <
      0.05) and oxygen consumption (VO2) reached a plateau after the third lap during
      TGlittre. The other physiological variables, except respiratory exchange rate,
      were similar at the end of both tests (p > 0.05). All measured variables were
      significantly correlated between the 2 tests (p < 0.05). CONCLUSION: TGlittre can
      induce slightly higher oxygen uptake than the 6MWT with similar cardiovascular
      and ventilatory demand and ventilatory efficiency.

PMID- 24104461
TI  - Alcohol and sexual risk reduction interventions among people living in Russia: a
      systematic review and meta-analysis.
AB  - Russia has one of the highest rates of alcohol consumption and is experiencing
      one of the fastest-growing HIV epidemics in the world. Given these co-occurring
      health problems, we systematically reviewed combined alcohol and sexual risk
      interventions to reduce HIV among Russians. We completed comprehensive electronic
      searches to locate studies that (a) sampled people living in Russia, (b) used a
      behavioral intervention, and (c) assessed both alcohol and sexual risk behavior.
      These searches yielded 584 studies, of these, two were included. Compared with
      controls, intervention participants reported increasing their condom use (ds
      ranged from 0.12 to 0.85). Within-group improvements in sexual behaviors were
      found for both groups (ds ranged from 0.19 to 1.94); participants reported fewer
      sexual partners, more condom use, and reduced alcohol or drug use before sex.
      These findings support the need and potential benefits for alcohol and HIV
      interventions among Russians, and suggest directions for public policy. 

PMID- 24104463
TI  - Hypoglycemic and hypolipidemic effects of protein hydrolysates from zebra blenny
      (Salaria basilisca) in alloxan-induced diabetic rats.
AB  - The present study investigates the hypoglycemic and hypolipidemic effects of
      protein hydrolysates obtained from zebra blenny (Salaria basilisca) muscles
      treated with three different crude alkaline protease extracts in alloxan-induced
      diabetic rats (AIDR). Analysis of amino acid composition revealed that zebra
      blenny protein hydrolysates (ZBPHs) were valuable sources of essential amino
      acids and rich in leucine, which is one of the active ingredients for blood
      glucose control by inducing insulin release in both rats and humans. Treatment of
      AIDR with ZBPHs revealed a significant inhibition of alpha-amylase activity in
      serum and the intestine, as well as a reduction of blood glucose and glycated
      hemoglobin (HbA1c) levels in diabetic rats. Further, ZBPHs also decreased
      significantly the triglyceride (TG), total-cholesterol (TC) and LDL-cholesterol
      (LDL-c) levels in the serum and liver of diabetic rats, while they increased the
      HDL-cholesterol (HDL-c) level, which helped to maintain the homeostasis of blood
      lipids. Furthermore, ZBPHs exhibited potent protective effects against heart
      attack markers by reversing myocardial enzyme serum back to normal levels. ZBPHs
      may also exert significant protective effects on liver function, evidenced by a
      marked decrease in the level of serum bilirubin as well as in the activities of
      alanine aminotransferase (ALT), alkaline phosphatase (ALP), and gamma-glutamyl
      transpeptidase (GGT). These beneficial effects of ZBPHs were confirmed by
      histological findings in the hepatic and pancreatic tissues of diabetic rats.
      Indeed, they avoid lipid accumulation in the hepatocytes and protect the
      pancreatic beta-cells from degeneration. Overall, the findings of the current
      study indicate that ZBPHs significantly attenuated hyperglycemia and
      hyperlipidemia in AIDR. 

PMID- 24104464
TI  - Coordination-driven nanosized lanthanide 'Molecular Lanterns' as luminescent
      chemosensors for the selective sensing of magnesium ions.
AB  - Novel cerium-based 'Molecular Lanterns' Ce-DBDS, Ce-DBBS and Ce-DBOS were
      achieved via self-assembly from bis-tridentate ligands H4DBDS, H4DBBS and H4DBOS,
      respectively. Structure analysis of Ce-DBDS shows that six oxygen atoms of the
      ether bond groups on the ligands form a lantern-like cavity inside the compound.
      Thus the 'Molecular Lanterns' exhibit crown ether recognition behavior and could
      be applied in luminescent magnesium chemosensors. The restricted geometry
      constraints of the internal cavities provide high selectivities of the lantern
      like probes towards the Mg(2+) ion over other different-sized metal ions such as
      Al(3+), Li(+), Ca(2+), Na(+), Ba(2+) and K(+). Ce-DBBS which contains three fully
      substituted benzyl groups exhibited better sensitivity by the cation-pi
      interaction between Mg(2+) and the benzyl group, compared to the Ce-DBDS.
      However, Ce-DBOS can work as an artificial chemosensor for selective fluorescent
      detection of Al(3+) rather than Mg(2+), due to its cavity being much smaller than
      Ce-DBDS and Ce-DBBS.

PMID- 24104466
TI  - Soft truncation thresholding for gene set analysis of RNA-seq data: application
      to a vaccine study.
AB  - Gene set analysis (GSA) has been used for analysis of microarray data to aid the
      interpretation and to increase statistical power. With the advent of next
      generation sequencing, the use of GSA is even more relevant, as studies are often
      conducted on a small number of samples. We propose the use of soft truncation
      thresholding and the Gamma Method (GM) to determine significant gene set (GS),
      where a generalized linear model is used to assess per-gene significance. The
      approach was compared to other methods using an extensive simulation study and
      RNA-seq data from smallpox vaccine study. The GM was found to outperform other
      proposed methods. Application of the GM to the smallpox vaccine study found the
      GSs to be moderately associated with response, including focal adhesion (p =
      0.04) and extracellular matrix receptor interaction (p = 0.05). The application
      of GSA to RNA-seq data will provide new insights into the genomic basis of
      complex traits. 

PMID- 24104467
TI  - Growth of Kluyveromyces marxianus and formation of ethyl acetate depending on
      temperature.
AB  - Conversion of lactose into ethyl acetate by Kluyveromyces marxianus allows
      economic reuse of whey-borne sugar. The high volatility of ethyl acetate enables
      its process-integrated recovery by stripping. This stripping is governed by both
      the aeration rate and the partition coefficient, K EA,L/G. Cultivation at
      elevated temperatures should decrease the K EA,L/G value and thus favor
      stripping. K. marxianus DSM 5422 as a potent producer of ethyl acetate was
      cultivated aerobically in whey-borne media for studying temperature-dependent
      growth and ester formation. Shake flask cultivation proved thermal tolerance of
      this yeast growing from 7 to 47  degrees C with a maximum rate of 0.75 h(-1) at
      40  degrees C. The biomass yield was 0.41 g/g at moderate temperatures while low
      and high temperatures caused distinct drops. The observed MU-T and Y X/S-T
      dependencies were described by mathematical models. Further cultivations were
      done in an 1-L stirred reactor for exploring the effect of temperature on ester
      synthesis. Cultivation at 32  degrees C caused significant ester formation (Y
      EA/S = 0.197 g/g) while cultivation at 42  degrees C suppressed ester synthesis
      (Y EA/S = 0.002 g/g). The high temperature affected metal dissolution from the
      bioreactor delivering iron for yeast growth and preventing ester synthesis.
      Cultivation at 32  degrees C with a switch to 42  degrees C at the onset of ester
      synthesis allowed quick and efficient ester production (Y EA/S = 0.289 g/g). The
      high temperature lowered the K EA,L/G value from 78 to 44 L/L which heightened
      the gas-phase ester concentration (favoring ester recovery) without increasing
      the liquid-phase concentration (avoiding product inhibition).

PMID- 24104468
TI  - Optimization of arylacetonitrilase production from Alcaligenes sp. MTCC 10675 and
      its application in mandelic acid synthesis.
AB  - Alcaligenes sp. MTCC 10675 has been isolated from soil sample using enrichment
      method and has nitrilase catalytic system which is highly specific for the
      hydrolysis of arylaliphatic nitriles. Optimization of culture conditions using
      response surface methodology and inducer-mediated approach enhanced
      arylacetonitrilase production significantly (2.4-fold). Isobutyronitrile acted as
      an effective inducer for the induction of arylacetonitrilase, and it is highly
      specific for arylacetonitriles (phenyl acetonitrile and mandelonitrile).
      Arylacetonitrilase has no effect on its relative velocity (V r) up to 20 mM
      substrate (mandelonitrile) concentration and at 30 mM mandelonitrile, 23.4 %
      degree of inhibition (I d) was recorded. Half life of arylacetonitrilase of
      Alcaligenes sp. MTCC 10675 was 27.5 h at 25  degrees C. Hg(2+), Ag(+), Pb(3+),
      and Co(2+) were strong inhibitor of arylacetonitrilase activity which resulted
      into 100 %, 91 %, 84 %, and 83 % inhibition, respectively. Polar protic solvent
      (dichloromethane, dimethylsulphooxide, and n-butanol) reduce arylacetonitrilase
      activity up to 80-94 % at 10 % concentration. Alcaligenes sp. MTCC 10675 has
      higher biocatalytic activity, i.e., 3.9 gg(-1) dcw, which is highest in
      comparison to till reported organism. Arylacetonitrilase-mediated hydrolysis of
      racemic mandelonitrile resulted into R-(-) mandelic acid with 99.0 % enantiomeric
      excess (e.e.).

PMID- 24104465
TI  - Seasonal H3N2 influenza A virus fails to enhance Staphylococcus aureus co
      infection in a non-human primate respiratory tract infection model.
AB  - Staphylococcus aureus community-acquired pneumonia is often associated with
      influenza or an influenza-like syndrome. Morbidity and mortality due to
      methicillin-resistant S. aureus (MRSA) or influenza and pneumonia, which includes
      bacterial co-infection, are among the top causes of death by infectious diseases
      in the United States. We developed a non-lethal influenza A virus (IAV) (H3N2)/S.
      aureus co-infection model in cynomolgus macaques (Macaca fascicularis) to test
      the hypothesis that seasonal IAV infection predisposes non-human primates to
      severe S. aureus pneumonia. Infection and disease progression were monitored by
      clinical assessment of animal health; analysis of blood chemistry, nasal swabs,
      and X-rays; and gross pathology and histopathology of lungs from infected
      animals. Seasonal IAV infection in healthy cynomolgus macaques caused mild
      pneumonia, but unexpectedly, did not predispose these animals to subsequent
      severe infection with the community-associated MRSA clone USA300. We conclude
      that in our co-infection model, seasonal IAV infection alone is not sufficient to
      promote severe S. aureus pneumonia in otherwise healthy non-human primates. The
      implication of these findings is that comorbidity factors in addition to IAV
      infection are required to predispose individuals to secondary S. aureus
      pneumonia. 

PMID- 24104469
TI  - The biophysical model for accuracy of cellular sensing spatial gradients of
      multiple chemoattractants.
AB  - Spatial gradients of surrounding chemoattractants are the key factors in
      determining the directionality of eukaryotic cell movement. Thus, it is important
      for cells to accurately measure the spatial gradients of surrounding
      chemoattractants. Here, we study the precision of sensing the spatial gradients
      of multiple chemoattractants using cooperative receptor clusters. Cooperative
      receptors on cells are modeled as an Ising chain of Monod-Wyman-Changeux clusters
      subject to multiple chemical-gradient fields to study the physical limits of
      multiple chemoattractants spatial gradients sensing. We found that eukaryotic
      cells cannot sense each chemoattractant gradient individually. Instead, cells can
      only sense a weighted sum of surrounding chemical gradients. Moreover, the
      precision of sensing one chemical gradient is signicantly affected by coexisting
      chemoattractant concentrations. These findings can provide a further insight into
      the role of chemoattractants in immune response and help develop novel treatments
      for inflammatory diseases. 

PMID- 24104470
TI  - Gadd45 in stress signaling, cell cycle control, and apoptosis.
AB  - The first identified Gadd45 gene, Gadd45a, encodes a ubiquitously expressed
      protein that is often induced by DNA damage and other stress signals associated
      with growth arrest and apoptosis. This protein and the other two members of this
      small gene family, Gadd45b and Gadd45g, have been implicated in a variety of the
      responses to cell injury including cell cycle checkpoints, apoptosis, and DNA
      repair. In vivo, many of the prominent roles for the Gadd45 proteins are
      associated with signaling mediated by p38 mitogen-activated protein kinases
      (MAPK). Gadd45 proteins can contribute to p38 activation either by activation of
      upstream kinase(s) or by direct interaction. In vivo, there are important tissue
      and cell-type-specific differences in the roles for Gadd45 in MAPK signaling. In
      addition to being p53-regulated, Gadd45a has been found to contribute to p53
      activation via p38. Like other stress and signaling proteins, Gadd45 proteins
      show complex regulation and numerous effectors. 

PMID- 24104471
TI  - Gadd45 in modulation of solid tumors and leukemia.
AB  - The stress response gadd45 gene family participates in cell cycle control, cell
      survival, apoptosis, maintenance of genomic stability, DNA repair, and active DNA
      demethylation, in response to environmental and physiological stress including
      oncogenic stress. Given these diverse functions, it is anticipated that gadd45
      genes can influence the initiation and progression of malignancy and the response
      to different treatments. This chapter will provide an overview of how the
      different members of the gadd45 gene family are expressed in different tumors and
      leukemia, how this may impact on progression of disease, and what happens when
      expression is manipulated. Studies from human tumor/leukemia samples, cell lines,
      and animal models are included in this review. An overriding theme is that each
      of the gadd45 genes has both tumor suppressor and tumor promoter functions,
      dependent on the tissue/cell type and transforming event. 

PMID- 24104472
TI  - Gadd45 proteins: key players of repair-mediated DNA demethylation.
AB  - The three growth arrest and DNA damage 45 (Gadd45) family genes encode for stress
      response proteins that are rapidly induced upon cellular stress or
      differentiation cues. They are well-characterized regulators of cell cycle,
      senescence, survival, and apoptosis. More recently, it has become clear that
      Gadd45 proteins promote active DNA demethylation thereby mediating gene
      activation. This epigenetic function of Gadd45 is important for differentiation
      and transcriptional regulation during development. Mechanistically, Gadd45 acts
      as an adapter for DNA repair factors at gene-specific loci to promote removal of
      5-methylcytosine from DNA. Hence, Gadd45 is a nexus between DNA repair and
      epigenetic gene regulation. 

PMID- 24104473
TI  - Gadd45 proteins in immunity.
AB  - The vertebrate immune system protects the host against invading pathogens such as
      viruses, bacteria and parasites. It consists of an innate branch and an adaptive
      branch that provide immediate and long-lasting protection, respectively. As the
      immune system is composed of different cell types and distributed throughout the
      whole body, immune cells need to communicate with each other. Intercellular
      communication in the immune system is mediated by cytokines, which bind to
      specific receptors on the cell surface and activate intracellular signalling
      networks. Growth arrest and DNA damage-inducible 45 (Gadd45) proteins are
      important components of these intracellular signalling networks. They are induced
      by a number of cytokines and by bacterial lipopolysaccharide. Within the innate
      immune system, Gadd45 proteins are crucial for the differentiation of myeloid
      cells as well as for the function of granulocytes and macrophages. Moreover,
      Gadd45beta regulates autophagy, a catabolic pathway that also degrades
      intracellular pathogens. Regarding adaptive immunity, Gadd45 proteins are
      especially well characterized in T cells. For instance, Gadd45beta and
      Gadd45gamma regulate cytokine expression and Th1 differentiation, while
      Gadd45alpha inhibits p38 kinase activation downstream of the T cell receptor. Due
      to their many functions in the immune system, deficiency in Gadd45 proteins
      causes autoimmune diseases and less efficient tumour immunosurveillance. 

PMID- 24104474
TI  - Gadd45 in the liver: signal transduction and transcriptional mechanisms.
AB  - Injury and growth stimulation both remarkably increase the hepatic expression of
      Gadd45beta. In liver cancer, promoter methylation frequently silences Gadd45beta,
      demonstrating due to a suppressive function that is often proapoptotic. This
      contrasts with normal hepatocytes, where Gadd45beta facilitates cell survival,
      growth, and proliferation. Gadd45beta binds MKK7-downstream of TNFalpha and its
      receptors-to prevent this kinase from activating JNK2. Hence, the Gadd45b-/-
      genotype increases cell injury and decreases cell proliferation during liver
      regeneration (i.e., compensatory growth and proliferation). Liver hyperplasia
      (i.e., de novo growth and proliferation) is an alternate form of growth, caused
      by drugs that activate the nuclear receptor, CAR. As in regeneration, the Gadd45b
      /- genotype considerably slows growth during hyperplasia. However, there is no
      injury and the slowing occurs because Gadd45beta normally binds to CAR and
      activates its transcriptional stimulation. Thus, Gadd45beta protects the liver
      through two entirely different processes: binding MKK7 to block damaging signal
      transduction or binding CAR to coactivate anabolic transcription. 

PMID- 24104475
TI  - The role of the Gadd45 family in the nervous system: a focus on neurodevelopment,
      neuronal injury, and cognitive neuroepigenetics.
AB  - The growth arrest and DNA damage-inducible (Gadd)45 proteins have been associated
      with numerous cellular mechanisms including cell-cycle control, DNA damage
      sensation and repair, genotoxic stress, neoplasia, and molecular epigenetics. The
      genes were originally identified in in vitro screens of irradiation- and
      interleukin-induced transcription and have since been implicated in a host of
      normal and aberrant central nervous system processes. These include early and
      postnatal development, injury, cancer, memory, aging, and neurodegenerative and
      psychiatric disease states. The proteins act through a variety of molecular
      signaling cascades including the MAPK cascade, cell-cycle control mechanisms,
      histone regulation, and epigenetic DNA demethylation. In this review, we provide
      a comprehensive discussion of the literature implicating each of the three
      members of the Gadd45 family in these processes. 

PMID- 24104476
TI  - Gadd45 stress sensors in preeclampsia.
AB  - Preeclampsia is a pregnancy-induced complex of multiple pathological changes.
      Numerous stresses during pregnancy, including hypoxia, immune activation,
      inflammatory cytokines, and oxidative stress were reported as contributing
      factors to the preeclamptic pathology. Seeking common sensors of various
      stressors in preeclampsia is of new interest and can potentially benefit in
      disease prevention and treatment. Recent studies have highlighted the role of the
      Gadd45a protein as a stress sensor in preeclampsia. In response to various
      pathophysiological stressors, notably hypoxia, inflammatory cytokines, and AT1
      AAs, Gadd45a activates Mkk3-p38 and or JNK signaling. This, in turn, results in
      immunological and inflammatory changes as well as triggering the production of
      circulating factors such as sFlt-1, which are believed to account for many of the
      pathophysiological-related symptoms of preeclampsia. Activation of
      inflammatory/immune responses in preeclampsia may function in a feedback loop to
      maintain elevated expression of Gadd45a protein. 

PMID- 24104477
TI  - A competitive protein interaction network buffers Oct4-mediated differentiation
      to promote pluripotency in embryonic stem cells.
AB  - Pluripotency in embryonic stem cells is maintained through the activity of a
      small set of transcription factors centred around Oct4 and Nanog, which control
      the expression of 'self-renewal' and 'differentiation' genes. Here, we combine
      single-cell quantitative immunofluorescence microscopy and gene expression
      analysis, together with theoretical modelling, to investigate how the activity of
      those factors is regulated. We uncover a key role for post-translational
      regulation in the maintenance of pluripotency, which complements the well
      established transcriptional regulatory layer. Specifically, we find that the
      activity of a network of protein complexes involving Nanog, Oct4, Tcf3, and beta
      catenin suffices to account for the behavior of ES cells under different
      conditions. Our results suggest that the function of the network is to buffer the
      transcriptional activity of Oct4, which appears to be the main determinant to
      exit pluripotency. The protein network explains the mechanisms underlying the
      gain and loss of function in different mutants, and brings us closer to a full
      understanding of the molecular basis of pluripotency. 

PMID- 24104478
TI  - Natural sequence variants of yeast environmental sensors confer cell-to-cell
      expression variability.
AB  - Living systems may have evolved probabilistic bet hedging strategies that
      generate cell-to-cell phenotypic diversity in anticipation of environmental
      catastrophes, as opposed to adaptation via a deterministic response to
      environmental changes. Evolution of bet hedging assumes that genotypes
      segregating in natural populations modulate the level of intraclonal diversity,
      which so far has largely remained hypothetical. Using a fluorescent P(met17)-GFP
      reporter, we mapped four genetic loci conferring to a wild yeast strain an
      elevated cell-to-cell variability in the expression of MET17, a gene regulated by
      the methionine pathway. A frameshift mutation in the Erc1p transmembrane
      transporter, probably resulting from a release of laboratory strains from
      negative selection, reduced P(met17)-GFP expression variability. At a second
      locus, cis-regulatory polymorphisms increased mean expression of the Mup1p
      methionine permease, causing increased expression variability in trans. These
      results demonstrate that an expression quantitative trait locus (eQTL) can
      simultaneously have a deterministic effect in cis and a probabilistic effect in
      trans. Our observations indicate that the evolution of transmembrane transporter
      genes can tune intraclonal variation and may therefore be implicated in both
      reactive and anticipatory strategies of adaptation.

PMID- 24104481
TI  - Chronic kidney disease in general populations and primary care: diagnostic and
      therapeutic considerations.
AB  - PURPOSE OF REVIEW: The majority of people with chronic kidney disease (CKD) are
      managed by primary care physicians and nurses, but much of the initial research
      on CKD care was based in secondary care. The purpose of this article is to review
      the important recent studies of CKD in primary care that are starting to provide
      an evidence base for the strategies to improve the management and outcomes of the
      unreferred majority of people with CKD. RECENT FINDINGS: People with CKD in
      primary care populations differ substantially from those familiar to
      nephrologists in secondary care by being older, having less reduction in
      glomerular filtration rate (GFR) and lower prevalence of proteinuria. These
      differences have important implications for management priorities. Detailed
      studies have identified widespread deficiencies in the care of patients with CKD
      in primary care (though these are also reported in secondary care). Interventions
      that may improve performance include automated reporting of estimated GFR,
      incentivizing primary care practitioners to achieve therapeutic goals and quality
      improvement strategies such as audit-based education. SUMMARY: Studies have
      identified a need for improved management of CKD in primary care as well as
      methods to achieve this. Future studies should focus on the promotion of self
      management through telemedicine and the Internet.

PMID- 24104479
TI  - A negative genetic interaction map in isogenic cancer cell lines reveals cancer
      cell vulnerabilities.
AB  - Improved efforts are necessary to define the functional product of cancer
      mutations currently being revealed through large-scale sequencing efforts. Using
      genome-scale pooled shRNA screening technology, we mapped negative genetic
      interactions across a set of isogenic cancer cell lines and confirmed hundreds of
      these interactions in orthogonal co-culture competition assays to generate a high
      confidence genetic interaction network of differentially essential or
      differential essentiality (DiE) genes. The network uncovered examples of
      conserved genetic interactions, densely connected functional modules derived from
      comparative genomics with model systems data, functions for uncharacterized genes
      in the human genome and targetable vulnerabilities. Finally, we demonstrate a
      general applicability of DiE gene signatures in determining genetic dependencies
      of other non-isogenic cancer cell lines. For example, the PTEN(-/-) DiE genes
      reveal a signature that can preferentially classify PTEN-dependent genotypes
      across a series of non-isogenic cell lines derived from the breast, pancreas and
      ovarian cancers. Our reference network suggests that many cancer vulnerabilities
      remain to be discovered through systematic derivation of a network of
      differentially essential genes in an isogenic cancer cell model. 

PMID- 24104480
TI  - Temporal control of self-organized pattern formation without morphogen gradients
      in bacteria.
AB  - Diverse mechanisms have been proposed to explain biological pattern formation.
      Regardless of their specific molecular interactions, the majority of these
      mechanisms require morphogen gradients as the spatial cue, which are either
      predefined or generated as a part of the patterning process. However, using
      Escherichia coli programmed by a synthetic gene circuit, we demonstrate here the
      generation of robust, self-organized ring patterns of gene expression in the
      absence of an apparent morphogen gradient. Instead of being a spatial cue, the
      morphogen serves as a timing cue to trigger the formation and maintenance of the
      ring patterns. The timing mechanism enables the system to sense the domain size
      of the environment and generate patterns that scale accordingly. Our work defines
      a novel mechanism of pattern formation that has implications for understanding
      natural developmental processes. 

PMID- 24104483
TI  - The relationship between tort reform and medical utilization.
AB  - INTRODUCTION: The hidden cost of defensive medicine has been cited by
      policymakers as a significant driving force in the increase of our nation's
      health-care costs. If this hypothesis is correct, one would expect that states
      with higher levels of tort reform will have a decrease in Medicare utilization
      and that medical utilization will decrease after tort reform is enacted. METHODS:
      State-level reimbursement data for years 1999 to 2010 (the last year available)
      was obtained from the Dartmouth Atlas of Health Care. Medical tort rankings for
      the 50 states were obtained from the Pacific Research Institute (PRI) and
      correlated with state medical utilization for the year 2010. In 3 states,
      Mississippi, Nevada, and Texas, data were available to make pretort and posttort
      reform comparisons. RESULTS: Data analysis between total state Medicare
      Reimbursements and the PRI's tort rankings showed no significant observed
      correlation. In 6 Medicare utilization categories (total Medicare, hospital and
      skilled nursing facility, physician, home health agency, hospice, and durable
      medical equipment), a negative trend was observed when correlated with PRI tort
      rankings. This trend does not support the hypothesis that defensive medicine is a
      major driver of health-care expenditures. Tracking expenditures in the states of
      Texas, Nevada, and Mississippi, before and after passage of comprehensive medical
      tort reform gave inconsistent results and did not demonstrate substantial or
      meaningful total Medicare savings. In Mississippi, there was a trend of decreased
      expenditures after medical tort reform was passed. However, in Texas, where 80%
      of the analyzed enrollees resided, there was a trend of progressive increasing
      expenditures after tort reform was passed. CONCLUSION: The comparison of the
      Dartmouth Atlas Medicare Reimbursement Data with Malpractice Reform State
      Rankings, which are used by the PRI, did not support the hypothesis that
      defensive medicine is a driver of rising health-care costs. Additionally,
      comparing Medicare reimbursements, premedical and postmedical tort reform, we
      found no consistent effect on health-care expenditures. Together, these data
      indicate that medical tort reform seems to have little to no effect on overall
      Medicare cost savings.

PMID- 24104484
TI  - A stable dual-functional system of visible-light-driven Ni(II) reduction to a
      nickel nanoparticle catalyst and robust in situ hydrogen production.
AB  - A stable hydrogen photogeneration system containing fluorescein as a
      photosensitizer with nickel(II) chloride as a catalyst precursor in basic
      solution was found to undergo in situ photoreduction of nickel(II) to zero-valent
      Ni nanoparticles to catalyze highly efficient hydrogen evolution under visible
      light irradiation.

PMID- 24104486
TI  - Modeling and analysis of high-performance, multicolored anti-reflection coatings
      for solar cells.
AB  - In this work solar cell anti-reflection coatings tuned to give a specific hue
      under solar illumination are investigated. We demonstrate that it is possible to
      form patterned coatings with large color contrast and high transmittance. We use
      colorimetric and thin film optics models to explore the relationship between the
      color and performance of bilayer anti-reflection coatings on Si, and predict the
      photocurrent generation from an example Si solar cell. The colorimetric
      predictions were verified by measuring a series of coatings deposited on Si
      substrates. Finally, a patterned Si sample was produced using a simple, low-cost
      photolithography procedure to selectively etch only the top layer of a bilayer
      coating to demonstrate a high-performance anti-reflection coating with strong
      color contrast. 

PMID- 24104485
TI  - Molecular and culture dependent characterization of endolithic bacteria in two
      beach sand samples and description of Rhizobium endolithicum sp. nov.
AB  - Endolithic metagenome analysis of two beach samples collected form Chilika,
      Odisha, India indicated rich bacterial diversity. While the metagenome analysis
      of sample one yielded 16S rRNA gene sequences which represent six phyla and 16
      genera, sample two yielded very rich diversity representing 17 phyla and 286
      genera. Six species of bacteria were isolated from the endolithic enrichments and
      most of them have 16S rRNA gene sequence similarity of >99 % with known taxa,
      except for strain JC140(T) having <97 % sequence similarity with taxa with valid
      names. Strain JC140(T) is Gram-stain-negative and motile. 16S rRNA gene based
      EzTaxon-e BLAST analysis indicated that strain JC140(T) is closely related with
      the type strains of Rhizobium yanglingense SH22623(T) (96.8 %), R. alkalisoli
      CCBAU 01393(T) (96.3 %), R. vignae CCBAU 05176(T) (96.2 %), R. mesosinicum CCBAU
      25010(T) (96.1 %) and other members of the genus Rhizobium with <96 % sequence
      similarity. Strain JC140(T) was characterized based on polyphasic taxonomic
      analysis. Strain JC140(T) could tolerate up to 5 % salinity, resistant to
      rifampicin (10 MUg) and was positive for catalase and oxidase. The major fatty
      acid is summed feature 8 (C18:1omega7c/C18:1omega6c) with minor amounts of C19:0
      cycloomega8c, C16:0, C18:0, C17:0cyclo, summed feature 2 (C14:03OH/C16:1 isoI),
      summed feature 3 (C16:1omega7c/C16:1omega6c) and 2-hydroxyacid of C15:0.
      Diphosphatidylglycerol, phosphatidylethanol-amine, phosphatidylcholine,
      phosphatidylglycerol, unidentified lipids (L1, 2), unidentified phospholipid (PL1
      4) constitute the polar lipids of strain JC140(T). The strain has bacteriohopane
      derivative (BHD2), diplopterol and two unidentified hopanes (UH1, 2) as major
      hopanoids. Q-10 is the major quinone of strain JC140(T). Based on polyphasic
      taxonomic analysis, strain JC140(T) represents a species in the genus Rhizobium
      for which, the name R. endolithicum sp. nov. is proposed. The type strain is
      JC140(T) (= KCTC32077(T) = CCUG64352(T) = MTCC11723(T) = HAMBI 2447(T)).

PMID- 24104487
TI  - Light trapping in periodically textured amorphous silicon thin film solar cells
      using realistic interface morphologies.
AB  - The influence of realistic interface morphologies on light trapping in amorphous
      silicon thin-film solar cells with periodic surface textures is studied.
      Realistic interface morphologies are obtained by a 3D surface coverage algorithm
      using the substrate morphology and layer thicknesses as input parameters. Finite
      difference time domain optical simulations are used to determine the absorption
      in the individual layers of the thin-film solar cell. The influence of realistic
      interface morphologies on light trapping is determined by using solar cells
      structures with the same front and back contact morphologies as a reference.
      Finally the optimal surface textures are derived. 

PMID- 24104488
TI  - Surface-concentrated light and efficient carrier collection in microhole
      patterned Si solar cells.
AB  - We investigate photovoltaic characteristics of crystalline Si solar cells with
      microhole-patterned surface. We compare patterned samples with different hole
      widths and periods with a planar counterpart. From the finite-difference time
      domain simulation, the patterned and planar samples are expected to have similar
      short circuit current density, J(sc) (difference: 1.2%). In contrast, the
      difference in the measured J(sc) is as large as 12.6%. The simulated optical
      field patterns reveal that the sample with more significantly concentrated light
      near the surface has higher quantum efficiency due to more efficient carrier
      collection. We report the highest efficiency of 15.6% among the hole-patterned
      solar cells.

PMID- 24104489
TI  - First-principle calculation of solar cell efficiency under incoherent
      illumination.
AB  - Because of the temporal incoherence of sunlight, solar cells efficiency should
      depend on the degree of coherence of the incident light. However, numerical
      computation methods, which are used to optimize these devices, fundamentally
      consider fully coherent light. Hereafter, we show that the incoherent efficiency
      of solar cells can be easily analytically calculated. The incoherent efficiency
      is simply derived from the coherent one thanks to a convolution product with a
      function characterizing the incoherent light. Our approach is neither heuristic
      nor empiric but is deduced from first-principle, i.e. Maxwell's equations.
      Usually, in order to reproduce the incoherent behavior, statistical methods
      requiring a high number of numerical simulations are used. With our method, such
      approaches are not required. Our results are compared with those from previous
      works and good agreement is found. 

PMID- 24104490
TI  - Fabrication of resonant patterns using thermal nano-imprint lithography for thin
      film photovoltaic applications.
AB  - A single-step, low-cost fabrication method to generate resonant nano-grating
      patterns on poly-methyl-methacrylate (PMMA; plexiglas) substrates using thermal
      nano-imprint lithography is reported. A guided-mode resonant structure is
      obtained by subsequent deposition of thin films of transparent conductive oxide
      and amorphous silicon on the imprinted area. Referenced to equivalent planar
      structures, around 25% and 45% integrated optical absorbance enhancement is
      observed over the 450-nm to 900-nm wavelength range in one- and two-dimensional
      patterned samples, respectively. The fabricated elements provided have 300-nm
      periods. Thermally imprinted thermoplastic substrates hold potential for low-cost
      fabrication of nano-patterned thin-film solar cells for efficient light
      management. 

PMID- 24104491
TI  - Illumination performance and energy saving of a solar fiber optic lighting
      system.
AB  - The illumination performance and energy savings of a solar fiber optic lighting
      system have been verified in a study hall--corridor interior. The system provides
      intensive white light with a high luminous flux of 4500 lm under 130000 lx direct
      sun radiation at a 10 m fiber distance from the sun-tracking light collector. The
      color temperature that describes the light color perceived is 5800 +/- 300 K,
      i.e. close to the direct sunlight outside, and the color rendering index (86),
      that describes how well colors are rendered under the light source, is higher for
      the solar lights than for the supplementary fluorescent lights (77). Thus this
      high quality solar lighting improves the visibility of all kinds of objects
      compared to the fluorescent lights. Annual lighting energy savings of 19% in
      Uppsala, Sweden and 46% in southern Europe were estimated for a study hall
      interior, as well as 27% and 55% respectively in an interior illuminated 16 h per
      day all days of a year.

PMID- 24104492
TI  - Designing optimized nano textures for thin-film silicon solar cells.
AB  - Thin-film silicon solar cells (TFSSC), which can be manufactured from abundant
      materials solely, contain nano-textured interfaces that scatter the incident
      light. We present an approximate very fast algorithm that allows optimizing the
      surface morphology of two-dimensional nano-textured interfaces. Optimized nano
      textures scatter the light incident on the solar cell stronger leading to a
      higher short-circuit current density and thus efficiency. Our algorithm combines
      a recently developed scattering model based on the scalar scattering theory, the
      Perlin-noise algorithm to generate the nano textures and the simulated annealing
      algorithm as optimization tool. The results presented in this letter allow to
      push the efficiency of TFSSC towards their theoretical limit. 

PMID- 24104493
TI  - Optical design of transparent metal grids for plasmonic absorption enhancement in
      ultrathin organic solar cells.
AB  - Transparent metal grid combining with plasmonic absorption enhancement is a
      promising replacement to indium tin oxide thin films. We numerically demonstrate
      metal grids in one or two dimension lead to plasmonic absorption enhancements in
      ultrathin organic solar cells. In this paper, we study optical design of metal
      grids for plasmonic light trapping and identify different plasmonic modes of the
      surface plasmon polaritons excited at the interfaces of glass/metal grids, metal
      grids/active layers, and the localized surface plasmon resonance of the metal
      grids using numerical calculations. One dimension metal grids with the optimal
      design of a width and a period lead to the absorption enhancement in the
      ultrathin active layers of 20 nm thickness by a factor of 2.6 under transverse
      electric polarized light compared to the case without the metal grids. Similarly,
      two dimensional metal grids provide the absorption enhancement by a factor of 1.8
      under randomly polarized light. 

PMID- 24104494
TI  - Broadband, polarization-insensitive and wide-angle absorption enhancement of a
      Si:H/MUc-Si:H tandem solar cells by nanopatterning a-Si:H layer.
AB  - A photonic crystal design that significantly enhances the absorption of tandem
      thin-film solar cells composed by amorphous and microcrystalline silicon (i.e., a
      Si:H/MUc-Si:H tandem cell) is proposed. The top junction with a-Si:H is
      nanopatterned as a one-dimensional photonic crystal. Considering the photocurrent
      matching, we optimally design the junction thickness and the configuration of the
      nanopattern; moreover, both transverse electric and magnetic incidences with
      various illuminating angles are taken into account. Calculations by rigorous
      coupled-wave approach and finite-element method show that the nanophotonic
      crystal design can improve the absorption and output photocurrent by over 20%,
      which shows very low sensitivity to the incident polarization. Moreover, the
      proposed structure is able to sustain the performance for a very wide angle
      ranges from 0 degrees  to ~80 degrees . 

PMID- 24104495
TI  - CCT- and CRI-tuning of white light-emitting diodes using three-dimensional non
      close-packed colloidal photonic crystals with photonic stop-bands.
AB  - This study exhibited the correlated color temperature (CCT)- and color-rendering
      index (CRI)-tuning behavior of light emission from white light-emitting diodes
      (WLEDs) using three-dimensional non-close-packed (3D NCP) colloidal photonic
      crystals (CPhCs). The CCT of approximately 5300 K (characteristic of cold WLEDs)
      of white light propagated through the NCP CPhCs dropped to 3000 K (characteristic
      of warm WLEDs) because of the photonic stop-bands based on the photonic band
      structures of NCP CPhCs. This study successfully developed a novel technique that
      introduces lower-cost CCT- and CRI-tuning cold WLEDs with a CRI of over 90 that
      of warm WLEDs by using 3D NCP CPhCs. 

PMID- 24104496
TI  - The three A symmetry Raman modes of kesterite in Cu2ZnSnSe4.
AB  - We investigate CZTSe films by polarization dependent Raman spectroscopy. The main
      peaks at 170 cm(-1), and 195 cm(-1) are found to have A symmetry. The Raman
      signal at 170 cm(-1) is found to be composed of two modes at 168 cm(-1) and 172
      cm(-1). We attribute these three Raman peaks to the three A symmetry modes
      predicted for kesterite ordered Cu(2)ZnSnSe(4). The main Raman peak is
      asymmetrically broadened towards lower energies. Possible sources of the
      broadening are tested through temperature and depth dependent measurements. The
      broadening is attributed to phonon confinement effects related to the presence of
      lattice defects.

PMID- 24104497
TI  - Effect of laser pulse energy on orthogonal double femtosecond pulse laser-induced
      breakdown spectroscopy.
AB  - In this paper, the effect of laser pulse energy on orthogonal double femtosecond
      pulse laser induced breakdown spectroscopy (LIBS) in air is studied. In the
      experiment, the energy of the probe pulse is changeable, while the pump pulse
      energy is held constant. At the same time, a systematic study of the laser
      induced breakdown spectroscopy signal dependence on the inter-pulse delay between
      the two pulses is performed. It is noted that the double pulse orthogonal
      configuration yields 2-32 times signal enhancement for the ionic and atomic lines
      as compared to the single pulse LIBS spectra when an optimum temporal separation
      between the two pulses is used, while there is no significant signal enhancement
      for the molecular lines in the studied range of the delay. It is also noted that
      the dependence of the enhancement factor for ionic and atomic lines on the inter
      pulse delay can be fitted by Gaussian function. Furthermore, the electron
      temperature obtained by the relative line-to-continuum intensity ratio method was
      used to explain the LIBS signal enhancement. 

PMID- 24104498
TI  - Enhanced efficiency of light-trapping nanoantenna arrays for thin-film solar
      cells.
AB  - We suggest a new type of efficient light-trapping structures for thin-film solar
      cells based on arrays of planar nanoantennas operating far from their plasmon
      resonances. The operation principle of our structures relies on the excitation of
      collective modes of the nanoantenna arrays whose electric field is localized
      between the adjacent metal elements. We calculate a substantial enhancement of
      the short-circuit photocurrent for photovoltaic layers as thin as 100-150 nm. We
      compare our light-trapping structures with conventional anti-reflecting coatings
      and demonstrate that our design approach is more efficient. We show that it may
      provide a general background for different types of broadband light-trapping
      structures compatible with large-area fabrication technologies for thin-film
      solar cells. 

PMID- 24104499
TI  - Temperature dependent emission and absorption cross section of Yb3+ doped yttrium
      lanthanum oxide (YLO) ceramic and its application in diode pumped amplifier.
AB  - Temperature dependent absorption and emission cross-sections of 5 at% Yb(3+)
      doped yttrium lanthanum oxide (Yb:YLO) ceramic between 80K and 300 K are
      presented. In addition, we report on the first demonstration of ns pulse
      amplification in Yb:YLO ceramic. A pulse energy of 102 mJ was extracted from a
      multi-pass amplifier setup. The amplification bandwidth at room temperature
      confirms the potential of Yb:YLO ceramic for broad bandwidth amplification at
      cryogenic temperatures.

PMID- 24104500
TI  - DNA repair gene XRCC3 polymorphisms and bladder cancer risk: a meta-analysis.
AB  - The X-ray repair cross-complementing group 3 (XRCC3) in homologous recombination
      repair (HRR) pathway plays a vital role in DNA double-strand break repair (DSBR).
      Variants in the XRCC3 gene might result in altered protein structure or function
      which may influence DSBR efficiency and lead to cancer. Numerous epidemiological
      studies have been conducted to evaluate the association between XRCC3
      polymorphisms and bladder cancer risk. However, the results of these previous
      studies have been inconsistent. To derive a more precise estimation of the
      association, we performed a meta-analysis of all available studies relating XRCC3
      polymorphisms and bladder cancer. All studies published up to April 2013 on the
      association between XRCC3 polymorphisms and bladder cancer risk were identified
      by searching electronic databases PubMed, EMBASE, and Chinese Biomedical
      Literature databases. The association between the XRCC3 polymorphisms and bladder
      cancer risk was assessed by odds ratios (ORs) together with their 95% confidence
      intervals (CIs). A total of 16 case-control studies met the inclusion criteria
      and were selected. With respect to C18067T polymorphism, significant increased
      bladder cancer risk was found when all eligible studies were pooled into the meta
      analysis (TT vs. CC: OR = 1.174, 95%CI = 1.033-1.335, P = 0.014 and recessive
      model TT vs. TC + CC: OR = 1.147, 95%CI = 1.020-1.290, P = 0.022, respectively).
      The results were still significant after excluding the Hardy-Weinberg equilibrium
      violation studies (TT vs. CC: OR = 1.178, 95%CI = 1.036-1.339, P = 0.013 and
      recessive model TT vs. TC + CC: OR = 1.144, 95%CI = 1.017-1.287, P = 0.025,
      respectively). In subgroup analysis by ethnicity, significant elevated risk was
      found among Asians (dominant model TT + TC vs. CC: OR = 1.285, 95%CI = 1.012
      1.631). In the subgroup analyses according to smoking status, no significant
      association was detected in all genetic comparison models. With respect to
      A17893G and A4541G polymorphisms, no significant association with bladder cancer
      risk was observed in the overall and subgroup analyses. This meta-analysis
      suggests that the XRCC3 C18067T polymorphism was associated with increased
      bladder cancer risk especially among Asians. However, the XRCC3 A17893G and
      A4541G polymorphisms may not play important roles in bladder carcinogenesis.
      Further studies with larger sample sizes are needed to validate our finds.

PMID- 24104501
TI  - The CIK cells stimulated with combination of IL-2 and IL-15 provide an improved
      cytotoxic capacity against human lung adenocarcinoma.
AB  - Generation of cytokine-induced killer (CIK) cells is an emerging approach in
      adoptive donor lymphocyte infusion for patients with a wide range of tumors.
      However, our previous in vitro studies have shown that the killing efficacy of
      CIK cells against lung cancer was lower than other tumor cells, while the
      underlying mechanisms are not clear. We explored the feasibility to improve CIK
      cells mediated cytotoxicity against lung cancer. Interleukin (IL)-15 is a
      pleiotropic cytokine that stimulates cytolytic activity and cytokine secretion of
      NK cells, which may enhance the cytotoxic activity of CIK cells. In this study,
      we intended to stimulate the CIK cells by IL-2 in combination with IL-15 in cell
      expansion to achieve enhanced cytotoxicity against lung cancer cells. The
      different phenotypes of IL-2 or combination of IL-2 and IL-15 stimulated cytokine
      induced killer cells were determined, and the improved cytotoxicity of IL-2 and
      IL-15 induced CIK cells against lung adenocarcinoma were evaluated both in vitro
      and in vivo. CIK cells stimulated with both IL-2 and IL-15 has shown greater
      proliferative potential than CIK cells treated with IL-2 alone. IL-15 induction
      also has driven the expansion of CD3+CD56+ subset and significantly enhanced
      cytotoxicity against tumor cells. Further analysis has demonstrated that CIKIL
      2&IL-15 injected mice models have shown significant tumor regression and lower
      expression level of CyclinD1 in tumor tissue. This study has provided preclinical
      evidences that CIKIL-2&IL-15 with enhanced cytotoxicity may offer alternative
      treatment option for patients with lung cancer. 

PMID- 24104502
TI  - Models of acute mucosal tolerance to radiotherapy alone applied to synchronous
      chemoradiation schedules in head and neck cancer.
AB  - Three models defining mucosal tolerance when radiotherapy alone is delivered have
      been published. Modelling studies have converted the contribution of synchronous
      chemotherapy to the rate of grade 3 mucositis to biologically effective dose
      (BED). The purpose of this study was to apply radiotherapy mucosal tolerance
      models to studies of synchronous chemoradiation. Trials of synchronous cisplatin
      and radiotherapy were identified. The BED for cell kill for each regime was
      calculated. Initially, this was done using the protocol parameters and a global
      value for the contribution of chemotherapy of 5.1 Gy10. These values were then
      compared with the BED cell kill ceiling values from each of the models calculated
      using the intended overall treatment time. These steps were then repeated using
      the delivered radiotherapy parameters and a value for the contribution from
      chemotherapy calculated to take into account dose intensity. Eight eligible
      treatment arms were identified. When using the intended radiotherapy parameters,
      six of these appeared to be tolerable when compared with the ceiling values for
      two of the models. All were found intolerable by one model. When using the actual
      delivered radiotherapy doses and overall treatment times and correcting for
      chemotherapy dose intensity, one treatment arm remained intolerable by all three
      models, a further treatment arm by two models and four treatment arms by one
      model. Two current models of mucosal tolerance derived from radiotherapy data
      predict a majority of previously reported chemoradiation study arms to be
      tolerable particularly when the delivered parameters are used for calculation. 

PMID- 24104503
TI  - The double-edged sword of grandiose narcissism: implications for successful and
      unsuccessful leadership among U.S. Presidents.
AB  - Recent research and theorizing suggest that narcissism may predict both positive
      and negative leadership behaviors. We tested this hypothesis with data on the 42
      U.S. presidents up to and including George W. Bush, using (a) expert-derived
      narcissism estimates, (b) independent historical surveys of presidential
      performance, and (c) largely or entirely objective indicators of presidential
      performance. Grandiose, but not vulnerable, narcissism was associated with
      superior overall greatness in an aggregate poll; it was also positively
      associated with public persuasiveness, crisis management, agenda setting, and
      allied behaviors, and with several objective indicators of performance, such as
      winning the popular vote and initiating legislation. Nevertheless, grandiose
      narcissism was also associated with several negative outcomes, including
      congressional impeachment resolutions and unethical behaviors. We found that
      presidents exhibit elevated levels of grandiose narcissism compared with the
      general population, and that presidents' grandiose narcissism has been rising
      over time. Our findings suggest that grandiose narcissism may be a double-edged
      sword in the leadership domain. 

PMID- 24104504
TI  - On the nature and nurture of intelligence and specific cognitive abilities: the
      more heritable, the more culture dependent.
AB  - To further knowledge concerning the nature and nurture of intelligence, we
      scrutinized how heritability coefficients vary across specific cognitive
      abilities both theoretically and empirically. Data from 23 twin studies (combined
      N = 7,852) showed that (a) in adult samples, culture-loaded subtests tend to
      demonstrate greater heritability coefficients than do culture-reduced subtests;
      and (b) in samples of both adults and children, a subtest's proportion of
      variance shared with general intelligence is a function of its cultural load.
      These findings require an explanation because they do not follow from mainstream
      theories of intelligence. The findings are consistent with our hypothesis that
      heritability coefficients differ across cognitive abilities as a result of
      differences in the contribution of genotype-environment covariance. The
      counterintuitive finding that the most heritable abilities are the most culture
      dependent abilities sheds a new light on the long-standing nature-nurture debate
      of intelligence. 

PMID- 24104505
TI  - Do age-related increases in tip-of-the-tongue experiences signify episodic memory
      impairments?
AB  - Tip-of-the-tongue experiences (TOTs), in which a name is known but cannot be
      immediately retrieved from memory, can be a cause of concern if these experiences
      are viewed as a sign of memory decline. The current study was conducted to
      investigate the relation between age and TOT frequency, and the influence of
      episodic memory, which is the type of memory most often assessed to detect memory
      problems, on that relation. In a sample of adults, increased age was found to be
      associated with more TOTs across different types of materials, and additional
      analyses suggested that these relations between age and TOT frequency were not
      attributable to the use of different response criteria or to different amounts of
      knowledge. Because statistical control of a measure of episodic memory had little
      effect on the relation between age and TOT frequency, age-related increases in
      TOTs and age-related decreases in episodic memory appear to be at least partially
      independent phenomena. 

PMID- 24104506
TI  - Turning body and self inside out: visualized heartbeats alter bodily self
      consciousness and tactile perception.
AB  - Prominent theories highlight the importance of bodily perception for self
      consciousness, but it is currently not known whether bodily perception is based
      on interoceptive or exteroceptive signals or on integrated signals from these
      anatomically distinct systems. In the research reported here, we combined both
      types of signals by surreptitiously providing participants with visual
      exteroceptive information about their heartbeat: A real-time video image of a
      periodically illuminated silhouette outlined participants' (projected, "virtual")
      bodies and flashed in synchrony with their heartbeats. We investigated whether
      these "cardio-visual" signals could modulate bodily self-consciousness and
      tactile perception. We report two main findings. First, synchronous cardio-visual
      signals increased self-identification with and self-location toward the virtual
      body, and second, they altered the perception of tactile stimuli applied to
      participants' backs so that touch was mislocalized toward the virtual body. We
      argue that the integration of signals from the inside and the outside of the
      human body is a fundamental neurobiological process underlying self
      consciousness. 

PMID- 24104507
TI  - The association between emotional and behavioral problems and gastrointestinal
      symptoms among children with high-functioning autism.
AB  - This study investigated the association between gastrointestinal symptoms and a
      broad set of emotional and behavioral concerns in 95 children with high
      functioning autism and IQ scores >= 80. Gastrointestinal symptoms were assessed
      via the Autism Treatment Network's Gastrointestinal Symptom Inventory, and data
      were gathered on autism symptom severity, adaptive behavior, and multiple
      internalizing and externalizing problems. The majority (61%) of children had at
      least one reported gastrointestinal symptom. Emotional and behavioral problems
      were also common but with a high degree of variability. Children with and without
      gastrointestinal problems did not differ in autism symptom severity, adaptive
      behavior, or total internalizing or externalizing problem scores. However,
      participants with gastrointestinal problems had significantly higher levels of
      affective problems. This finding is consistent with a small body of research
      noting a relationship between gastrointestinal problems, irritability, and mood
      problems in autism spectrum disorder. More research to identify the mechanisms
      underlying this relationship in autism spectrum disorder is warranted. Future
      research should include a medical assessment of gastrointestinal concerns,
      longitudinal design, and participants with a range of autism spectrum disorder
      severity in order to clarify the directionality of this relationship and to
      identify factors that may impact heterogeneity in the behavioral manifestation of
      gastrointestinal concerns.

PMID- 24104508
TI  - Parent reflections of experiences of participating in a randomized controlled
      trial of a behavioral intervention for infants at risk of autism spectrum
      disorders.
AB  - BACKGROUND: Despite the mounting evidence of efficacy of early intervention for
      children with autism spectrum disorders, there is little research that considers
      the various perceptions and resources with which parents respond to the pressures
      and opportunities associated with participation in early intervention. Research
      is particularly lacking surrounding experiences of parents with infants who are
      at risk of autism spectrum disorders but do not (yet) have a diagnosed condition.
      OBJECTIVES: This qualitative study aimed to explore the experiences of caregivers
      following their participation in a randomized controlled trial of Adapted
      Responsive Teaching, a parent-infant relationship-focused intervention for
      infants at risk of autism spectrum disorders in a community sample. Parents were
      randomized into either the treatment group, in which they participated in the
      Adapted Responsive Teaching intervention, or the community services group, in
      which they were provided with information regarding local early intervention
      services and were encouraged, but not required to, seek community services as
      part of their inclusion in the randomized controlled trial. METHODS:
      Semistructured interviews were conducted with families following the completion
      of the randomized controlled trial. Participants consisted of 13 mothers and 4
      fathers. Five dyads were interviewed together for a total of 14 families. Child
      ages ranged from 39 to 46 months at the time of interview. Analysis was conducted
      on 14 interviews from 10 families who were randomized into the treatment group
      and 4 families randomized into the community services group. Analysis was
      informed by a thematic analysis approach, which involved a systematic process of
      coding and theme identification both across and within groups. RESULTS: Themes
      that emerged across groups included Working against all odds, Value of the
      personal relationship, Getting the ball rolling, and Getting dad on board. One
      broad theme represented the data within the groups: Win-win (Adapted Responsive
      Teaching group) and Navigating amidst ambiguity (community services group).
      CONCLUSIONS: This study illuminates the personal experiences and contextual
      influences affecting families who are participating in the randomized controlled
      trial through early identification of "risk" status for autism spectrum disorders
      in their infants. Insights gained from these interviews may serve to refine and
      enhance intervention models and to enhance early intervention services for
      families.

PMID- 24104509
TI  - Pathological demand avoidance: exploring the behavioural profile.
AB  - 'Pathological Demand Avoidance' is a term increasingly used by practitioners in
      the United Kingdom. It was coined to describe a profile of obsessive resistance
      to everyday demands and requests, with a tendency to resort to 'socially
      manipulative' behaviour, including outrageous or embarrassing acts. Pathological
      demand avoidance is thought to share aspects of social impairment with autism
      spectrum disorders, but autism spectrum disorder-appropriate strategies, such as
      routine and repetition, are described as unhelpful. Outrageous acts and lack of
      concern for their effects draw parallels with conduct problems and callous
      unemotional traits. However, reward-based techniques, effective with conduct
      problems and callous-unemotional traits, seem not to work in pathological demand
      avoidance. Despite increasing interest and controversy over the pathological
      demand avoidance label, there is only one published study to date. We present the
      first systematic comparison of the behavioural profile of children receiving the
      term pathological demand avoidance (N = 25) to children with autism spectrum
      disorders (N = 39) or conduct problems and callous-unemotional traits (N = 28),
      using parent-report indices of psychopathology. The pathological demand avoidance
      group displayed comparable levels of autistic traits and peer problems to the
      autism spectrum disorders group and anti-social traits approaching those seen in
      the conduct problems and callous-unemotional traits group. Emotional symptoms in
      pathological demand avoidance exceeded both comparison groups. Findings highlight
      the extreme behavioural impairment associated with pathological demand avoidance
      and the need to explore whether behavioural overlap reflects a similar
      neurocognitive basis to existing groups.

PMID- 24104510
TI  - Video game access, parental rules, and problem behavior: a study of boys with
      autism spectrum disorder.
AB  - Environmental correlates of problem behavior among individuals with autism
      spectrum disorder remain relatively understudied. The current study examined the
      contribution of in-room (i.e. bedroom) access to a video game console as one
      potential correlate of problem behavior among a sample of 169 boys with autism
      spectrum disorder (ranging from 8 to 18 years of age). Parents of these children
      reported on (1) whether they had specific rules regulating their child's video
      game use, (2) whether their child had in-room access to a variety of screen-based
      media devices (television, computer, and video game console), and (3) their
      child's oppositional behaviors. Multivariate regression models showed that in
      room access to a video game console predicted oppositional behavior while
      controlling for in-room access to other media devices (computer and television)
      and relevant variables (e.g. average number of video game hours played per day).
      Additionally, the association between in-room access to a video game console and
      oppositional behavior was particularly large when parents reported no rules on
      their child's video game use. The current findings indicate that both access and
      parental rules regarding video games warrant future experimental and longitudinal
      research as they relate to problem behavior in boys with autism spectrum
      disorder.

PMID- 24104511
TI  - Correlation of cognitive and social outcomes among children with autism spectrum
      disorder in a randomized trial of behavioral intervention.
AB  - Although social impairments are considered the hallmark deficit of autism, many
      behavioral intervention studies rely on cognitive functioning as a primary
      outcome. Fewer studies have examined whether changes in cognition are associated
      with changes in social functioning. This study examined whether cognitive gains
      among 192 students from 47 kindergarten-through-second-grade autism support
      classrooms participating in a year-long behavioral intervention study were
      associated with gains in social functioning. Children's gains in cognitive
      ability were modestly associated with independent assessors' and teachers'
      evaluations of social functioning but were not associated with changes in parent
      ratings. Observed social gains were not commensurate with gains in cognition,
      suggesting the need both for interventions that directly target social
      functioning and relevant field measures of social functioning. 

PMID- 24104512
TI  - Demographic and clinical correlates of autism symptom domains and autism spectrum
      diagnosis.
AB  - Demographic and clinical factors may influence assessment of autism symptoms.
      This study evaluated these correlates and also examined whether social
      communication and interaction and restricted/repetitive behavior provided unique
      prediction of autism spectrum disorder diagnosis. We analyzed data from 7352
      siblings included in the Interactive Autism Network registry. Social
      communication and interaction and restricted/repetitive behavior symptoms were
      obtained using caregiver-reports on the Social Responsiveness Scale. Demographic
      and clinical correlates were covariates in regression models predicting social
      communication and interaction and restricted/repetitive behavior symptoms.
      Logistic regression and receiver operating characteristic curve analyses
      evaluated the incremental validity of social communication and interaction and
      restricted/repetitive behavior domains over and above global autism symptoms.
      Autism spectrum disorder diagnosis was the strongest correlate of caregiver
      reported social communication and interaction and restricted/repetitive behavior
      symptoms. The presence of comorbid diagnoses also increased symptom levels.
      Social communication and interaction and restricted/repetitive behavior symptoms
      provided significant, but modest, incremental validity in predicting diagnosis
      beyond global autism symptoms. These findings suggest that autism spectrum
      disorder diagnosis is by far the largest determinant of quantitatively measured
      autism symptoms. Externalizing (attention deficit hyperactivity disorder) and
      internalizing (anxiety) behavior, low cognitive ability, and demographic factors
      may confound caregiver-report of autism symptoms, potentially necessitating a
      continuous norming approach to the revision of symptom measures. Social
      communication and interaction and restricted/repetitive behavior symptoms may
      provide incremental validity in the diagnosis of autism spectrum disorder.

PMID- 24104513
TI  - See what I see, do as I do: promoting joint attention and imitation in
      preschoolers with autism spectrum disorder.
AB  - Since imitation and joint attention are both important abilities for young
      children and since children with autism spectrum disorder show a range of
      problems in these domains, imitation and joint attention are important targets
      for intervention. In this study, we examined the possibility of promoting
      imitation and joint attention by means of a training programme specifically
      designed for low-intensity, non-residential treatment. Two matched groups of 18
      children each participated in the study. The experimental group, receiving the
      training programme, improved significantly more on joint attention than the group
      receiving only treatment as usual. Only the experimental group obtained a
      significantly higher imitation score during the post-test compared to the pre
      test. This study shows that it is possible to promote joint attention with a low
      intensity treatment programme. The results concerning imitation are more modest.
      Future replications should involve measures of stability and generalization.

PMID- 24104514
TI  - Augmentative and alternative communication supports for adults with autism
      spectrum disorders.
AB  - Many adults with autism spectrum disorders have complex communication needs and
      may benefit from the use of augmentative and alternative communication. However,
      there is a lack of research examining the specific communication needs of these
      adults, let alone the outcomes of interventions aimed at addressing them. The aim
      of this study was to explore the views and experiences of support workers and
      family members regarding the outcomes of providing low-technology communication
      aids to adults with autism spectrum disorders. The participants were six support
      workers and two family members of six men and women with autism spectrum
      disorders, who had received low-technology communication aids. Using semi
      structured, in-depth interviews and following thematic analysis, the results
      revealed strong support for, and the potential benefits of, augmentative and
      alternative communication for both adults with autism spectrum disorders and
      their communication partners. The results also revealed inconsistencies in the
      actions taken to support the use of the prescribed augmentative and alternative
      communication systems, pointing to the clinical need to address common barriers
      to the provision of augmentative and alternative communication support. These
      barriers include organisational practices and limitations in the knowledge and
      skills of key stakeholders, as well as problematic attitudes. 

PMID- 24104515
TI  - Parenting stress and autism: the role of age, autism severity, quality of life
      and problem behaviour of children and adolescents with autism.
AB  - While stress is a common experience for parents caring for a child with a
      developmental disability, current measures fail to distinguish between general
      stress in parents and the demands of parenting and perceptions of parenting
      skills (parenting stress). This study examined differences in 'parenting stress'
      reported by parents of children with autism and typically developing children.
      This study examined the role of child characteristics (age, autism severity,
      child quality of life and problem behaviour) on parenting stress in 150 parents
      of cognitively able children and adolescents with autism. The results revealed
      that child hyperactivity was the only factor significantly related to parenting
      stress in parents of children with autism, overruling measures of autism severity
      and child quality of life. This finding indicates the significant influence of
      problematic behaviours on parenting demands and perceptions of parenting skills
      in parents of children with autism, over other child characteristics conceived as
      within the parent's control. Study implications for future research are
      discussed.

PMID- 24104516
TI  - Parents' views of the National Autistic Society's EarlyBird Plus Programme.
AB  - Parent training interventions are recommended for parents soon after their
      child's autism spectrum condition diagnosis with the aim of improving parents'
      psychological well-being and coping, as well as the child's behaviour. This
      report explores parents' views of the EarlyBird Plus Programme through data
      collected routinely in the post-programme questionnaire. Participants' reported
      increased understanding of autism and improvements in their communication with
      their child and their ability to manage their child's behaviour. Parents appeared
      to value the opportunity to meet with other parents, and the programme seemed
      acceptable to the majority of parents who attended.

PMID- 24104517
TI  - Pilot clinical application of an adaptive robotic system for young children with
      autism.
AB  - It has been argued that clinical applications of advanced technology may hold
      promise for addressing impairments associated with autism spectrum disorders.
      This pilot feasibility study evaluated the application of a novel adaptive robot
      mediated system capable of both administering and automatically adjusting joint
      attention prompts to a small group of preschool children with autism spectrum
      disorders (n = 6) and a control group (n = 6). Children in both groups spent more
      time looking at the humanoid robot and were able to achieve a high level of
      accuracy across trials. However, across groups, children required higher levels
      of prompting to successfully orient within robot-administered trials. The results
      highlight both the potential benefits of closed-loop adaptive robotic systems as
      well as current limitations of existing humanoid-robotic platforms. 

PMID- 24104518
TI  - The association between parental interaction style and children's joint
      engagement in families with toddlers with autism.
AB  - PURPOSE: This study examines the relationship between parental interaction style
      (responsive vs directive) and child-initiated joint engagement within caregiver
      child interactions with toddlers diagnosed with autism spectrum disorders.
      METHOD: Videotaped interactions of 85 toddler-caregiver dyads were coded for
      child engagement and both parental responsiveness and directiveness. RESULTS:
      Altogether, children spent less than one-third of the interaction jointly
      engaged. After controlling for child characteristics, parental style was
      associated with the initiator (child or parent) of joint engagement.
      Specifically, responsiveness predicted total time in child-initiated joint
      engagement, while directiveness predicted total time in parent-initiated joint
      engagement. Children's social behaviours were associated with child-initiated
      joint engagement. DISCUSSION: Social initiations are a key target for children
      with autism spectrum disorders. Results demonstrate that child initiations and
      global social behaviour ratings are associated with parental responsivity.
      Responsivity may be a critical factor to facilitate children's initiations.

PMID- 24104519
TI  - Explicit versus implicit social cognition testing in autism spectrum disorder.
AB  - Although autism spectrum disorder is defined by reciprocal social-communication
      impairments, several studies have found no evidence for altered social cognition
      test performance. This study examined explicit (i.e. prompted) and implicit (i.e.
      spontaneous) variants of social cognition testing in autism spectrum disorder. A
      sample of 19 adolescents with autism spectrum disorder and 19 carefully matched
      typically developing controls completed the Dewey Story Test. 'Explicit'
      (multiple-choice answering format) and 'implicit' (free interview) measures of
      social cognition were obtained. Autism spectrum disorder participants did not
      differ from controls regarding explicit social cognition performance. However,
      the autism spectrum disorder group performed more poorly than controls on
      implicit social cognition performance in terms of spontaneous perspective taking
      and social awareness. Findings suggest that social cognition alterations in
      autism spectrum disorder are primarily implicit in nature and that an apparent
      absence of social cognition difficulties on certain tests using rather explicit
      testing formats does not necessarily mean social cognition typicality in autism
      spectrum disorder.

PMID- 24104520
TI  - Commentary: the five Ws of a Fracture Liaison Service: why, who, what, where, and
      how? In osteoporosis, we reap what we sow.
AB  - Establishing a Fracture Liaison Service (FLS) to identify and treat patients with
      a recent fragility fracture has been shown to be effective, save money, useful to
      document high quality of care, and makes good clinical sense. A FLS starts with
      an osteoporosis champion and encompasses identification of patients with a recent
      fracture, diagnostic workup, treatment, and follow-up. A FLS is most effective
      when it is able to function in multiple settings: the hospital, emergency
      department, and outpatient clinic. Implementation may be somewhat easier in a
      closed healthcare system but can be feasible even in an open system. There are
      many barriers to implementation which can be addressed. The future of FLS care
      lies in a collaborative systems-based approach with appropriate stakeholder
      engagement, leading to seamless integration of osteoporosis care. 

PMID- 24104522
TI  - Substrate curvature sensing through Myosin IIa upregulates early osteogenesis.
AB  - Topographical cues mimicking the extracellular matrix (ECM) have demonstrated
      control over a diverse range of cellular behaviours including: initial adhesion,
      migration, cell growth, differentiation and death. How cells sense, and in turn
      translate, the topographical cues remains to be answered, but likely involves
      interactions through interfacial forces that influence cytoskeletal structure and
      integrin clustering, leading to the downstream activity of intracellular
      signalling cascades. Electrospun fibers have shown significant success as a
      biomimetic topography for bone tissue engineering applications, but mechanisms by
      which osteoprogenitor cells translate the fiber geometry into intracellular
      signalling activity is only recently being examined. We hypothesized that
      increased cellular differentiation observed on fibrous topography is due to acto
      myosin contractility and cellular stiffness via the small GTPase RhoA. In order
      to evaluate this hypothesis, MC3T3-E1 osteoprogenitor cells were grown on
      poly(methyl methacrylate) (PMMA) fibers of 1.153 +/- 0.310 MUm diameter. The
      elastic modulus of the cell surface was measured by atomic force microscopy (AFM)
      with a colloidal probe. Overall cellular stiffness was found to increase more
      than three-fold in osteoprogenitors adhered to a fiber, as opposed to those grown
      on a flat substrate. Pharmacological inhibition of RhoA signalling activity
      decreased cellular stiffness and cytoskeletal integrity of osteoprogenitors
      growing on fibrous substrates. Finally, we demonstrated not only RhoA activity
      through its effector Rho-associated coiled coil kinase II (ROCKII), but also
      Myosin IIa promotes early osteogenic differentiation, as shown by alkaline
      phosphatase (ALP) staining. Previous studies have demonstrated the importance of
      ROCKII on early differentiation. Our results shed light on mechanisms underlying
      geometry sensing by highlighting the role of Myosin IIa in addition to ROCKII and
      could ultimately contribute to scaffold design strategies. 

PMID- 24104523
TI  - H6phospa-trastuzumab: bifunctional methylenephosphonate-based chelator with 89Zr,
      111In and 177Lu.
AB  - The acyclic chelator H6phospa and the bifunctional derivative p-SCN-Bn-H6phospa
      have been synthesized using nosyl protection chemistry and evaluated with (89)Zr,
      (111)In, and (177)Lu. The p-SCN-Bn-H6phospa derivative was successfully
      conjugated to trastuzumab with isotopic dilution assays indicating 3.3 +/- 0.1
      chelates per antibody and in vitro cellular binding assays indicating an
      immunoreactivity value of 97.9 +/- 2.6%. Radiolabeling of the H6phospa
      trastuzumab immunoconjugate was achieved with (111)In in 70-90% yields at room
      temperature in 30 minutes, while (177)Lu under the same conditions produced more
      inconsistent yields of 40-80%. Stability experiments in human serum revealed the
      (111)In-phospa-trastuzumab complex to be 52.0 +/- 5.3% intact after 5 days at 37 
      degrees C, while the (177)Lu-phospa-trastuzumab to be only 2.0 +/- 0.3% intact.
      Small animal SPECT/CT imaging using mice bearing subcutaneous SKOV-3 ovarian
      cancer xenografts was performed, and it was found that (111)In-phospa-trastuzumab
      successfully identified and delineated small (~2 mm in diameter) tumors from
      surrounding tissues, despite visible uptake in the kidneys and bone due to
      moderate chelate instability. As predicted from stability assays in serum, the
      (177)Lu-phospa-trastuzumab conjugate served as a negative control and displayed
      no tumor uptake, with high uptake in bones indicating rapid and complete
      radiometal dissociation and suggesting a potential application of H6phospa in
      transient lanthanide chelation for bone-delivery. Radiolabeling with (89)Zr was
      attempted, but even with elevated temperatures of 37  degrees C, the maximum
      observed radiometal incorporation over 18 hours was 12%. It can be concluded from
      this work that H6phospa is not superior to the previously studied H4octapa for
      use with (111)In and (177)Lu, but improvements in (89)Zr radiolabeling were
      observed over H4octapa, suggesting H6phospa to be an excellent starting point for
      elaboration of (89)Zr-based radiopharmaceutical development. To our knowledge,
      H6phospa is the best desferrioxamine alternative for (89)Zr radiolabeling to be
      studied to date.

PMID- 24104524
TI  - Replication of a GWAS signal in a Caucasian population implicates ADD3 in
      susceptibility to biliary atresia.
AB  - In the United States, biliary atresia (BA) is the most frequent indication for
      liver transplantation in pediatric patients. BA is a complex disease, with
      suspected environmental and genetic risk factors. A genome-wide association study
      in Chinese patients identified association to the 10q24.2 (hg18) genomic region.
      This signal was upstream of two genes, XPNPEP1 and ADD3, both expressed in
      intrahepatic bile ducts. We tested association to this region in 171 BA patients
      and 1,630 controls of European descent and found the strongest signal to be at
      rs7099604 (p = 2.5 * 10(-3)) in intron 1 of the ADD3 gene. Moreover, expression
      data suggest that ADD3, but not XPNPEP1, is differentially expressed in BA
      patients. The role of ADD3 in biliary development is unclear, but our findings
      suggest that this gene may be functionally relevant for the development of BA.

PMID- 24104526
TI  - Carpal tunnel syndrome in pregnancy: a review.
AB  - The incidence of carpal tunnel syndrome in pregnant women reported in the
      literature varies from 2 to 70%. Hormonal fluctuations, fluid accumulation with
      tendency to oedemas, nerve hypersensitivity and glucose level fluctuations are
      factors that predispose pregnant women to the development of symptoms. The
      syndrome is rarely a matter of concern, as the symptoms are mild and no treatment
      is needed in majority of patients. The diagnosis is basically clinical and
      electrodiagnostic or sonographic testing provides no meaningful diagnostic aid.
      If necessary, the treatment starts with wrist splinting in the night, followed by
      steroid injection in the carpal tunnel. Most women experience symptomatic
      improvement following delivery or breastfeeding; however, some women may continue
      to experience symptoms for up to 3 years. 

PMID- 24104529
TI  - Lower limb spasticity assessment using an inertial sensor: a reliability study.
AB  - Spasticity is a common motor impairment in patients with neurological disorders
      that can prevent functional recovery after rehabilitation. In the clinical
      setting, its assessment is carried out using standardized clinical scales. The
      aim of this study was to verify the applicability of inertial sensors for an
      objective measurement of quadriceps spasticity and evaluate its test-retest and
      inter-rater reliability during the implementation of the Wartenberg pendulum
      test. Ten healthy subjects and 11 patients in vegetative state with severe brain
      damage were enrolled in this study. Subjects were evaluated three times on three
      consecutive days. The test-retest reliability of measurement was assessed in the
      first two days. The third day was devoted to inter-rater reliability assessment.
      In addition, the lower limb muscle tone was bilaterally evaluated at the knee
      joint by the modified Ashworth scale. The factorial ANOVA analysis showed that
      the implemented method allowed us to discriminate between healthy and
      pathological conditions. The fairly low SEM and high ICC values obtained for the
      pendulum parameters indicated a good test-retest and inter-rater reliability of
      measurement. This study shows that an inertial sensor can be reliably used to
      characterize leg kinematics during the Wartenberg pendulum test and provide
      quantitative evaluation of quadriceps spasticity. 

PMID- 24104530
TI  - [Examine of quality of life of elderly indivudals suffering pain].
AB  - OBJECTIVES: This study aims to examine the quality of life of elderly individuals
      suffering pain. METHODS: The study was carried out on 84 individuals over the age
      of 65 resident at a local authority administered nursing home in Izmir who were
      suffering pain at the time of the interview. The individuals' introduction form,
      made up of 12 questions, was used to identify the individuals' socio-demographic
      characteristics, and the McGill Melzack Pain Questionnaire was used to assess the
      pain, and the WHOQOL-OLD (World health Organization Quality of Life Scale Older
      Adults Module) was applied. RESULTS: A significant relationship was found between
      the current pain severity and the quality of life scale's sensory capacity,
      today's activities and future activities, and relationship sub-fields and the
      total points (p<0.05). CONCLUSION: It was established, as well as the elderly
      individuals' socio-demographic characteristics, sub-sections such as the
      features, severity and time of pain also had an effect on the quality of life.

PMID- 24104525
TI  - Cancer genomics identifies disrupted epigenetic genes.
AB  - Latest advances in genome technologies have greatly advanced the discovery of
      epigenetic genes altered in cancer. The initial single candidate gene approaches
      have been coupled with newly developed epigenomic platforms to hasten the
      convergence of scientific discoveries and translational applications. Here, we
      present an overview of the evolution of cancer epigenomics and an updated catalog
      of disruptions in epigenetic pathways, whose misregulation can culminate in
      cancer. The creation of these basic mutational catalogs in cell lines and primary
      tumors will provide us with enough knowledge to move diagnostics and therapy from
      the laboratory bench to the bedside. 

PMID- 24104531
TI  - [A comparison of vertical infraclavicular and coracoid approaches in forearm
      surgery].
AB  - OBJECTIVES: Despite several risks, infraclavicular approaches to the brachial
      plexus gained popularity. The present study compared success rates, block onset
      times, block performance times, and frequency of adverse effects of vertical
      infraclavicular (VIB) and coracoid blocks (CB) in patients undergoing forearm
      surgery. METHODS: After ethical committee approval and informed consent 40
      patients undergoing forearm surgery were included. The brachial plexus was
      located using a nerve stimulator and an insulated pencil point needle. Thirty ml
      bupivacaine 0.5% was used for the block. The blocks were assessed every minute
      for the first 5 min, then every 5 min for 15 min and then every 15 min and at the
      end of the operation. RESULTS: Block onset times of both groups were similar.
      Higher rates of sensory block were found in group CB at the 5th, 10th, and 15th
      minutes of assessment. Also higher rates of motor block were found in group CB at
      the 5th, 10th, 15th and 30th minutes of assessment. Time to perform block was
      shorter in group VIB. One patient in CB group required general anaesthesia.
      Except two vascular punctures in group CB no other side-effects were observed.
      CONCLUSION: Coracapid block provided higher rates of sensorial and motor blocks
      in a similar onset time without serious complications. CB can be accepted as a
      safe and reliable alternative to VIB for forearm surgery.

PMID- 24104527
TI  - Bevacizumab (BVZ)-associated toxicities in children with recurrent central
      nervous system tumors treated with BVZ and irinotecan (CPT-11): a Pediatric Brain
      Tumor Consortium Study (PBTC-022).
AB  - BACKGROUND: The incidence and spectrum of acute toxicities related to the use of
      bevacizumab (BVZ)-containing regimens in children are largely unknown. This
      report describes the adverse events in a recently completed large phase 2 trial
      of BVZ plus irinotecan (CPT-11) in children with recurrent central nervous system
      tumors. METHODS: Pediatric Brain Tumor Consortium trial-022 evaluated the
      efficacy and toxicity of BVZ (10 mg/kg administered intravenously) as a single
      agent for 2 doses given 2 weeks apart and then combined with CPT-11 every 2 weeks
      (1 course = 4 weeks) in children with recurrent central nervous system tumors.
      Children were treated until they experienced progressive disease, unacceptable
      toxicity or completed up to a maximum of 2 years of therapy. Toxicities were
      graded according to the National Cancer Institute Common Terminology Criteria for
      Adverse Events, version 3.0. Patients who received at least 1 dose of BVZ were
      included for toxicity assessment. RESULTS: Between October 2006 and June 2010, 92
      patients evaluable for toxicity were enrolled and received 687 treatment courses.
      The most common toxicities attributable to BVZ included grade I-III hypertension
      (38% of patients), grade I-III fatigue (30%), grade I-II epistaxis (24%), and
      grade I-IV proteinuria (22%). Twenty-two patients (24%) stopped therapy due to
      toxicity. CONCLUSIONS: The combination of BVZ and CPT-11 was fairly well
      tolerated, and most severe BVZ-related toxicities were rare, self-limiting, and
      manageable.

PMID- 24104532
TI  - [Comparison of ilioinguinal-iliohypogastric nerve block versus spinal anesthesia
      techniques for single sided inguinal herniorrhaphy].
AB  - OBJECTIVES: The aim of the study is to compare the hemodynamic effects,
      postoperative analgesia, time to achieve discharge criteria, and patient-surgeon
      satisfaction of patients who are assigned for single sided inguinal hernia repair
      operated under iliohypogastric ilioingiinal nerve block (IHNB) or spinal
      anesthesia. METHODS: Twenty-five ASA I-III patients in Group S received 15 mg
      0.5% hyperbaric bupivacaine intrathecally, and 25 ASA I-III patients in Group I
      received IHNB with 20 mL 0.5% plain bupivacaine. RESULTS: Mean block application
      duration (16.4+/-3 vs 6.5+/-2.1 min), mean sensory block rise time (25.2+/-5.1 vs
      6.9+/-3.4 min), and time to sensory block termination (262.4+/-65.2 vs 116.6+/
      102.5 min) was found to longer in Group I with respect to Group S (p<0.001). Mean
      time to first mobilization (307.1+/-146.9 vs 456.9+/-131.7 min), and mean time to
      meet discharge criteria (4.6+/-0.8 vs 8.1+/-2.7 hr) was shorter in group I. Mean
      VAS scores in postoperative 1, 2, 4 and 6 th and mean tramadole consumption in 24
      hr (375.6+/-113.1 vs 180.5+/-17.9 mg) were higher in Group S (p<0.001).
      Hemodynamic parameters, patient and surgeon satisfaction were comparable
      (p>0.05). CONCLUSION: IHNB provides longer postoperative analgesia and earliar
      discharge, although takes more time to perform and to produce maximum effect, for
      single sided inguinal henia repair.

PMID- 24104533
TI  - [Retrospective evaluation of the patients with chronic pain admitted to the
      algology polyclinic between 2000-2010].
AB  - OBJECTIVES: The aim of this study is to evaluate the patients who admitted to
      algology polyclinic with malign and non-malign pain, sociodemographic
      characteristics, type of pain and pain management retrospectively. METHODS: In
      this study we examined the medical assessement files of patients who admitted to
      our outpatient clinic of Algology Department for chronic pain between January
      2000- December 2010. The sociodemographic characteristics of the patients, pain
      properties and treatments were reviewed retrospectively. RESULTS: Within the
      eleven years period, a total of 6647 patients have been admitted to our clinic.
      66.9% of the patients were between the ages of 19 and 64. There was no
      significant difference between gender. The most common causes of pain were
      myofascial pain, neuropathic pain, low back pain and headache. Among malignancy
      related cases the most common sources were gastrointenstinal system, lung and
      breast regions. In 83.4% of patients, pharmacological and invasive treatments
      were utilized. The most common invasive treatment modalities were, trigger point
      injection, dry needle application and epidural catheter application. CONCLUSION:
      In conclusion, pain treatments with multidisciplinary approach applied by the
      increasing number of pain clinics provide favorouble results and patients quality
      of life is also increased. We hope our retrospective study may provide helpful
      data for future studies on chronic pain with its comprehensive base of patient
      data which covers an eleven years period.

PMID- 24104534
TI  - Results of the assessment of the council of multidisciplinary pain.
AB  - OBJECTIVES: The aim of this study was to emphasize the necessity of
      multidisciplinary pain council by demonstrating the patient profile, treatment
      approaches, outcomes, and patient satisfaction levels obtained from our council.
      METHODS: In this study, the age, gender, number of council evaluations, diagnoses
      and recommended therapies of patients were determined retrospectively. The status
      of the patients >1 year, outcomes of the therapies, and satisfaction levels of
      the patients were questioned on the phone. RESULTS: The patients were most
      commonly diagnosed as chronic low back pain (35%) and vertebral tumor or
      metastasis (10%). 74 % of the patients were evaluated because of vertebral
      causes. 23% of the patients had good, 27% had moderate and 35% had poor benefit;
      beneficence was calculated as 85%. Patient satisfaction was found as 24%, 23%,
      and 32%, respectively; satisfaction was calculated as 79%. CONCLUSION: Evaluation
      of complex patients by physicians from different disciplines has better
      diagnostic and treatment outcomes. In addition, multidisciplinary approach offer
      and perform different therapy options and this has positive effects on treatment
      efficiency and patient satisfaction. We are in the opinion that instead of
      standard treatment protocols, determining individualized multidisciplinary
      treatment protocols should be useful.

PMID- 24104535
TI  - [Postspinal subacute subdural hematoma: case report].
AB  - The development of intracranial subdural hematoma after spinal anesthesia is a
      rare and serious complication that can be fatal if untreated. Needle puncture to
      the dura mater can cause leakage of cerebrospinal fluid, and lead to stretching
      and rupture of the meningeal blood vessels with resultant bleeding. A 24-year-old
      patient, with a completely normal history and laboratory analysis, has got a L4-5
      level spinal anesthesia well done at first try, using a Quinke 25 G needle and
      12,5 mg bupivacaine heavy. The first day after spinal anesthesia, the patient
      started to have a headache. He applied to another hospital where he received
      conservative treatment with a diagnosis of post-spinal headache. But, persistence
      of the headache made the patient refer to our pain clinic. The headache was
      located behind the left ear non-postural in nature, and was associated with
      tinnitus. Emergency cranial computerized tomography was obtained and acute fronto
      temporo-parietal subdural hematoma was reported. After spinal anesthesia,
      continued atypical headache and presence of tinnitus must alert against an
      underlying subdural hematoma. Early diagnosis can be made by history of the
      patient combined with neurological and radiological imaging methods. 

PMID- 24104536
TI  - Combined use of ultrasound guided infraclavicular block and lateral femoral
      cutaneous nerve block in upper extremity reconstruction requiring large skin
      graft: case report.
AB  - Combined nerve blocks of the upper extremity and lower limb in same operation
      rarely performed due to the risk of systemic toxicity of local anesthetics.
      Therefore, general anesthesia is generally preferred in this operations. However,
      use of ultrasound allows reliable deposition of the anesthetic around the nerves,
      potentially lowering the local anesthetic requirement. In this case report, we
      present a 44-year-old, ASA physical status I, male patient who was operated for
      upper extremity reconstruction requiring skin graft from anterolateral thigh
      region under ultrasound-guided infraclavicular brachial plexus block and lateral
      femoral cutaneous nerve block. The block was successful and no block-related
      complications were noted. We think that combining an ultrasound guided
      infraclavicular brachial plexus block and a lateral femoral cutaneous nerve block
      is a clinically useful and safe technique and an alternative anesthetic method
      for procedures requiring skin grafts for the upper extremity. 

PMID- 24104537
TI  - [The epidural blood patch technique for the management of headache due to
      spontaneous intracranial hypotension].
AB  - Spontaneous intracranial hypotension is a clinical entity characterized by
      orthostatic headache, low CSF pressure and specific cranial imaging techniques.
      Headache can be accompanied by the symptoms such as tinnitus, vertigo, diplopia,
      nausea and vomiting. It is important for the diagnosis to show the level of CSF
      leakage. Epidural blood patch should be planned for the treatment of patients
      with no reduction of the complaints following conservative treatment. In this
      case report, we have discussed the diagnostic methods of spontaneous intracranial
      hypotension and the importance of an epidural blood patch for its treatment in
      the light of the literature. 

PMID- 24104538
TI  - A case of cerebral venous thrombosis accompanying with intracranial hypotension:
      headache that changing character.
AB  - Spontaneous intracranial hypotension was first described by Schalternbarn. Severe
      complications like cerebral venous thrombosis and subdural hemorrhage are
      seldomly seen. A 40-year-old man was examined for weakness of right arm started 9
      months earlier and aggravated in last 3 months. He was undergo a lumbar punction
      because of a demyelinating plaque at C2 level in MRI. After 10 days of lumbar
      punction he experienced a generalised tonic clonic seizure. At cranial MRI and
      venography thrombosed superior sagittal and right transverse sinus and image of
      pachymeningitis, caused by intracranial hypotension were observed. Coincidence of
      these two situations together was seldomly found at literature. Thrombosis can
      both effect the sinuses and cortical veins. Spontaneous intracranial hypotension
      is a risk factor for CVT, but at only 2% CVT is seen as a complication. We think
      that our case can add addition to literature by having this coincidence. 

PMID- 24104539
TI  - Ultrasound guided brachial plexus block can be advantageous in patients with
      avulsion type upper extremity injuries.

PMID- 24104542
TI  - Acute apnea swimming: metabolic responses and performance.
AB  - Competitive swimmers regularly perform apnea series with or without fins as part
      of their training, but the ergogenic and metabolic repercussions of acute and
      chronic apnea have not been examined. Therefore, we aimed to investigate the
      cardiovascular, lactate, arterial oxygen saturation and hormonal responses to
      acute apnea in relation to performance in male swimmers. According to a
      randomized protocol, 15 national or regional competitive swimmers were monitored
      while performing four 100-m freestyle trials, each consisting of four 25-m
      segments with departure every 30 seconds at maximal speed in the following
      conditions: with normal frequency breathing with fins (F) and without fins (S)
      and with complete apnea for the four 25-m segments with (FAp) and without fins
      (SAp). Heart rate (HR) was measured continuously and arterial oxygen saturation,
      blood, and saliva samples were assessed after 30 seconds, 3 minutes, and 10
      minutes of recovery, respectively. Swimming performance was better with fins than
      without both with normal frequency breathing and apnea (p < 0.001). Apnea induced
      no change in lactatemia, but a decrease in arterial oxygen saturation in both SAp
      and FAp (p < 0.001) was noted and a decrease in HR and swimming performance in
      SAp (p < 0.01). During apnea without fins, performance alteration was correlated
      with bradycardia (r = 0.63) and arterial oxygen desaturation (r = -0.57). Saliva
      dehydroepiandrosterone was increased compared with basal values whatever the
      trial (p <= 0.05), whereas no change was found in saliva cortisol or
      testosterone. Further studies are necessary to clarify the fin effect on HR and
      performance during apnea swimming.

PMID- 24104541
TI  - Wide-ranging barcoding aids discovery of one-third increase of species richness
      in presumably well-investigated moths.
AB  - Rapid development of broad regional and international DNA barcode libraries have
      brought new insights into the species diversity of many areas and groups. Many
      new species, even within well-investigated species groups, have been discovered
      based initially on differences in DNA barcodes. We barcoded 437 collection
      specimens belonging to 40 pre-identified Palearctic species of the Elachista
      bifasciella group of moths (Lepidoptera, Elachistidae). Although the study group
      has been a subject of several careful morphological taxonomic examinations, an
      unexpectedly high number of previously undetected putative species is revealed,
      resulting in a 34% rise in species number in the study area. The validity of
      putative new species was subsequently supported with diagnostic morphological
      traits. We show that DNA barcodes provide a powerful method of detecting
      potential new species even in taxonomic groups and geographic areas that have
      previously been under considerable morphological taxonomic scrutiny. 

PMID- 24104540
TI  - Protein tyrosine phosphatase PTP1B in cell adhesion and migration.
AB  - Cell migration requires a highly coordinated interplay between specialized plasma
      membrane adhesion complexes and the cytoskeleton. Protein
      phosphorylation/dephosphorylation modifications regulate many aspects of the
      integrin-cytoskeleton interdependence, including their coupling, dynamics, and
      organization to support cell movement. The endoplasmic reticulum-bound protein
      tyrosine phosphatase PTP1B has been implicated as a regulator of cell adhesion
      and migration. Recent results from our laboratory shed light on potential
      mechanisms, such as Src/FAK signaling through Rho GTPases and integrin
      cytoskeletal coupling. 

PMID- 24104543
TI  - T-lymphocytes are directly involved in the clinical expression of migratory
      circinate erythema in epidermolysis bullosa simplex patients.
AB  - Epidermolysis bullosa simplex with migratory circinate erythema (EBS-MCE) is a
      rare EBS subtype characterised by migratory blistering lesions that resolve with
      brownish pigmentation. It is caused by a recurrent readthrough mutation,
      c.1649delG, in the tail of keratin 5. Here, we report a child with EBS-MCE and
      investigated the immunologic mechanisms underlying the migratory lesions in this
      patient. A skin biopsy from the patient from an active border of an erythematous
      lesion was used for the immunohistochemical characterisation of the inflammatory
      infiltrate and for TUNEL assay to detect apoptotic cells. We found abundant CD4+
      and CD8+ T lymphocytes infiltrating the papillary dermis and lining the dermal
      epidermal junction. A number of these cells expressed the activation marker CD69.
      CD83+ dendritic cells were present both in the epidermis and papillary dermis.
      Finally, TUNEL staining showed apoptosis of basal and suprabasal keratinocytes.
      These findings suggest a critical role of the cellular immunity in determining
      the EBS-MCE phenotype.

PMID- 24104549
TI  - Blue two-photon fluorescence metal cluster probe precisely marking cell nuclei of
      two cell lines.
AB  - A bifunctional peptide was designed to in situ reduce Cu ions and anchor a Cu
      cluster. The peptide-Cu cluster probe, mainly composed of Cu14, emitted blue two
      photon fluorescence under femtosecond laser excitation. Most important, the probe
      can specifically mark the nuclei of HeLa and A549 cells, respectively. 

PMID- 24104550
TI  - Deregulation of cancer-related miRNAs is a common event in both benign and
      malignant human breast tumors.
AB  - MicroRNAs (miRNAs) are endogenous non-coding RNAs, which play an essential role
      in the regulation of gene expression during carcinogenesis. The role of miRNAs in
      breast cancer has been thoroughly investigated, and although many miRNAs are
      identified as cancer related, little is known about their involvement in benign
      tumors. In this study, we investigated miRNA expression profiles in the two most
      common types of human benign tumors (fibroadenoma/fibroadenomatosis) and in
      malignant breast tumors and explored their role as oncomirs and tumor suppressor
      miRNAs. Here, we identified 33 miRNAs with similar deregulated expression in both
      benign and malignant tumors compared with the expression levels of those in
      normal tissue, including breast cancer-related miRNAs such as let-7, miR-21 and
      miR-155. Additionally, messenger RNA (mRNA) expression profiles were obtained for
      some of the same samples. Using integrated mRNA/miRNA expression analysis, we
      observed that overexpression of certain miRNAs co-occurred with a significant
      downregulation of their candidate target mRNAs in both benign and malignant
      tumors. In support of these findings, in vitro functional screening of the
      downregulated miRNAs in non-malignant and breast cancer cell lines identified
      several possible tumor suppressor miRNAs, including miR-193b, miR-193a-3p, miR
      126, miR-134, miR-132, miR-486-5p, miR-886-3p, miR-195 and miR-497, showing
      reduced growth when re-expressed in cancer cells. The finding of deregulated
      expression of oncomirs and tumor suppressor miRNAs in benign breast tumors is
      intriguing, indicating that they may play a role in proliferation. A role of
      cancer-related miRNAs in the early phases of carcinogenesis and malignant
      transformation can, therefore, not be ruled out. 

PMID- 24104551
TI  - Estrogen receptor alpha or beta loss in the colon of Min/+ mice promotes crypt
      expansion and impairs TGFbeta and HNF3beta signaling.
AB  - Adenomatous polyposis coli (APC)-regulated Wnt and transforming growth factor
      beta (TGFbeta) signaling cooperate in the intestine to maintain normal enterocyte
      functions. Human clinical trials showed that estrogen [17beta-estradiol (E2)],
      the ligand of nuclear receptors estrogen receptor alpha (ERalpha) and ERbeta,
      inhibited colorectal cancer (CRC) in women. Consistent with this finding, we
      reported that E2, ERalpha and ERbeta suppressed intestinal tumorigenesis in the
      C57BL/6J-Min/+ (Min/+) mouse, a CRC model. Here, we extended our results with
      further comparisons of colon and small intestine from intact female Apc (+/+)
      (WT), Min/+ and ER-deficient Min/+ mice. In the colon of ER-deficient Min/+ mice,
      ER loss reduced TGFbeta signaling in crypt base cells as evidenced by minimal
      expression of the effectors Smad 2, 3 and 4 in these strains. We also found
      reduced expression of Indian hedgehog (Ihh), bone morphogenetic protein 4 and
      hepatocyte nuclear factor 3beta or FoxA2, factors needed for paracrine signaling
      between enterocytes and mesenchyme. In proximal colon, ER loss produced a >10
      fold increased incidence of crypt fission, a marker for wound healing and tumor
      promotion. These data, combined with our previous work detailing the specific
      roles of E2, ERalpha and ERbeta in the colon, suggest that ER activity helps to
      maintain the intestinal stem cell (ISC) microenvironment by modulating epithelial
      stromal crosstalk in ways that regulate cytokine, Wnt and Ihh availability in the
      extracellular matrix (ECM). 

PMID- 24104552
TI  - Cooperative behavior of the nuclear receptor superfamily and its deregulation in
      prostate cancer.
AB  - The current study aimed to assess the topology of the nuclear receptor (NR)
      superfamily in normal prostate epithelial cells and its distortion in prostate
      cancer. Both in vitro and in silico approaches were utilized to profile NRs
      expressed in non-malignant RWPE-1 cells, which were subsequently investigated by
      treating cells with 132 binary NR ligand combinations. Nine significant
      cooperative interactions emerged including both superadditive [22(R)
      hydroxycholesterol and eicosatetraenoic acid] and subadditive [1alpha,25(OH)2D3
      and chenodeoxycholic acid] cellular responses, which could be explained in part
      by cooperative control of cell-cycle progression and candidate gene expression.
      In addition, publicly available data were employed to assess NR expression in
      human prostate tissue. Common and significant loss of NR superfamily expression
      was established in publicly available data from prostate tumors, in part
      predicting parallel distortion of targeting microRNA. These findings suggest that
      the NR superfamily in the prostate cooperatively integrates signals from dietary,
      hormonal and metabolic cues, and is significantly distorted in prostate cancer. 

PMID- 24104553
TI  - CYLD controls c-MYC expression through the JNK-dependent signaling pathway in
      hepatocellular carcinoma.
AB  - Posttranslational modification of different proteins via direct ubiquitin
      attachment is vital for mediating various cellular processes. Cylindromatosis
      (CYLD), a deubiquitination enzyme, is able to cleave the polyubiquitin chains
      from the substrate and to regulate different signaling pathways. Loss, or reduced
      expression, of CYLD is observed in different types of human cancer, such as
      hepatocellular carcinoma (HCC). However, the molecular mechanism by which CYLD
      affects cancerogenesis has to date not been unveiled. The aim of the present
      study was to examine how CYLD regulates cellular functions and signaling pathways
      during hepatocancerogenesis. We found that mice lacking CYLD were highly
      susceptible to chemically induced liver cancer. The mechanism behind proved to be
      an elevated proliferation rate of hepatocytes, owing to sustained c-Jun N
      terminal kinase 1 (JNK1)-mediated signaling via ubiquitination of TNF receptor
      associated factor 2 and expression of c-MYC. Overexpression of wild-type CYLD in
      HCC cell lines prevented cell proliferation, without affecting apoptosis,
      adhesion and migration. A combined immunohistochemical and tissue microarray
      analysis of 81 human HCC tissues revealed that CYLD expression is negatively
      correlated with expression of proliferation markers Ki-67 and c-MYC. To conclude,
      we found that downregulation of CYLD induces tumor cell proliferation,
      consequently contributing to the aggressive growth of HCC. Our findings suggest
      that CYLD holds potential to serve as a marker for HCC progression, and its link
      to c-MYC via JNK1 may provide the foundation for new therapeutic strategies for
      HCC patients. 

PMID- 24104554
TI  - Potentially functional variants of p14ARF are associated with HPV-positive
      oropharyngeal cancer patients and survival after definitive chemoradiotherapy.
AB  - Since p14 (ARF) and human papillomavirus (HPV) 16 E6/E7 oncoproteins are
      important regulators participating in the p53/Rb pathways, genetic variations of
      p14 (ARF) may modify tumor HPV16 status and survival of HPV16-positive squamous
      cell carcinoma of the oropharynx (SCCOP) patients. We determined tumor HPV16
      status and expression of p14/p53 and genotyped p14 (ARF) -rs3731217 and 
      rs3088440 polymorphisms in 552 incident SCCOP patients. We found that patients
      having variant genotypes for each p14 (ARF) polymorphism were approximately two
      or three times as likely to have HPV16-positive tumors compared with patients
      with corresponding common homozygous genotype, and such an association was
      particularly pronounced in patients with variant genotypes of both polymorphisms.
      After definitive chemoradiotherapy, patients having p14 (ARF) rs3731217 TG/GG
      variant genotypes had significantly better overall, disease-specific and disease
      free survival than those having TT genotype, respectively. Multivariable analysis
      found that patients with p14 (ARF) -rs3731217 TT genotype had an ~7-, 11- and 3
      fold increased risk for death overall, death due to SCCOP and recurrence than
      those with TG/GG variant genotypes, respectively. Furthermore, such significantly
      prognostic effect was also found when survival analysis was limited to HPV16
      positive patients. Additionally, potentially functional relevance of the two
      variants was characterized to explore the genotype-phenotype correlation. Our
      findings indicate p14 (ARF) variants may predict tumor HPV16-positive SCCOP
      patients and survival. 

PMID- 24104555
TI  - Geographic origins and dietary transitions during the Bronze Age in the Oman
      Peninsula.
AB  - The nature of the Bronze Age transition from the Umm an-Nar (ca. 2700-2000 BC) to
      the Wadi Suq (ca. 2000-1300 BC) period in the Oman Peninsula has been highly
      debated by archaeologists, with some characterizing the latter as a time of
      cultural isolation, social collapse, and/or population replacement following the
      successful involvement of the area in widespread interregional exchange networks
      across Arabia and South Asia. The hypothesis that a substantial change in
      residential mobility, immigration, and diet took place in response to
      considerable societal changes as reflected by the archaeological record was
      tested using stable oxygen and carbon isotope analysis. Archaeological human
      dental enamel from individuals interred in six Umm an-Nar (n = 100) and seven
      Wadi Suq (n = 16) communal tombs in the United Arab Emirates was used. Oxygen
      isotope data reveal largely homogeneous ratios indicative of a predominantly
      local population that acquired water from isotopically similar sources, although
      the presence of immigrants during both periods suggests that the region was not
      as isolated as previously held. Carbon isotope data exhibit a substantial
      temporal shift from an extremely varied to a more restricted diet, demonstrating
      that while considerable changes in subsistence strategies and social organization
      took place in the early second millennium BC, population continuity and sustained
      (although lessened) participation in pan-Gulf trade systems best characterizes
      this regional transformation.

PMID- 24104556
TI  - Letter in response to Dr Segal's commentary.

PMID- 24104557
TI  - Review: no evidence that stimulant medication for ADHD influences lifetime risk
      of substance use or dependence.

PMID- 24104558
TI  - Suicidal behaviours are common among US adolescents and are associated with
      mental health disorders.

PMID- 24104559
TI  - mRNAs and miRNAs profiling of mesenchymal stem cells derived from amniotic fluid
      and skin: the double face of the coin.
AB  - Mesenchymal stem cells (MSCs) can be isolated from different adult sources and,
      even if the minimal criteria for defining MSCs have been reported, the scientific
      question about the potential distinctions among MSCs derived from different
      sources is still open. In particular, it is debated whether MSCs of different
      origin have the same grade of stemness or whether the source affects their
      undifferentiated status. Here, we report not only the isolation and the
      traditional characterization of MSCs derived from amniotic fluid (AF-MSCs) and
      skin (S-MSCs) but also a molecular characterization based on mRNAs and miRNAs
      profiling. Our results show that, even if both AF- and S-MSCs are mostly
      regulated by the same pathways (such as Wnt, MAPK and TGF-beta), there are some
      important differences at the molecular level that directly affect important
      cellular features, such as the ability to differentiate into adipocytes. In
      conclusion, even if further studies are necessary to improve the knowledge about
      the role of each dysregulated miRNAs gene, these differences may actually
      strengthen the question about the importance of tissue origin. 

PMID- 24104560
TI  - Improvement of liver fibrosis by infusion of cultured cells derived from human
      bone marrow.
AB  - We develop "autologous bone marrow cell infusion (ABMi) therapy" for the
      treatment of human decompensated liver cirrhosis and confirm the efficacy and
      safety of this treatment in multicenter clinical studies. With the goal of
      further expanding the applications of ABMi, we first cultured human bone marrow
      cells and then determined whether a cell fraction found to be effective in
      improving liver fibrosis can be amplified. Cells harvested after two passages (P2
      cells) consistently contained approximately 94% mesenchymal stem cells (MSCs);
      conversely, the cells harvested after only medium change (P0 cells) contained
      many macrophages. MSCs (2.8 * 10(8)) in P2 cells were harvested from 3.8 * 10(8)
      bone marrow-derived mononuclear cells after 22 days. DNA-chip analysis also
      showed during the culturing step that bone marrow-derived cells decreased with
      macrophage phenotype. The infused 5 * 10(5) P2 cells significantly improved liver
      fibrosis in the nonobese diabetic/severe combined immunodeficient (NOD-SCID)
      mouse carbon tetrachloride (CCl4) liver cirrhosis model and induced the
      expression of matrix metalloproteinase (MMP)-9 and suppressed expressions of
      alpha smooth muscle actin (alphaSMA), tumor necrosis factor alpha (TNFalpha) and
      transforming growth factor beta (TGFbeta) in the liver. Cultured human bone
      marrow-derived cells (P2 cells) significantly inhibited liver fibrosis. The
      increase of MMP-9 and suppressed activation of hepatic stellate cells (HSCs)
      through the regulation of humoral factors (TNFalpha and TGFbeta) contribute to
      the improvement of liver fibrosis by MSCs comprising about 94% of P2 cells. MSCs
      in cultured human bone marrow-derived mono-nuclear cells (BM-MNCs) proliferate
      sufficiently in cell therapy, so we believe our cultured bone marrow-derived cell
      therapy can lead to expanded clinical applications and enable outpatient therapy.

PMID- 24104561
TI  - Preimplantation genetic diagnosis (PGD) influences adrenal development and
      response to cold stress in resulting mice.
AB  - Preimplantation genetic diagnosis (PGD) has gained widespread application in
      clinical medicine and hence the health of PGD offspring needs to be
      systematically assessed. Given the critical role of the stress response in growth
      and health, assessments of the development and function of the stress system
      might help to clarify the health outcomes of PGD. In this study, we constructed a
      PGD-conceived mouse model and used naturally conceived mice as controls; we used
      this model to evaluate the potential effect of PGD procedures on the stress
      system of the offspring. Serum and tissues of stress organs, namely the
      hypothalamus, locus coeruleus and adrenal gland, were collected from 5-week-old
      mice in the basal state or after cold stress. The serum levels of stress-related
      hormones and the structural and functional indices of the stress organs were then
      examined. In the basal state, ultrastructural abnormalities and low expression of
      genes involved in steroid hormone synthesis were found in the adrenals of the PGD
      mice, which had low corticosterone and high epinephrine levels compared with
      those of control mice. After acute cold stress, the PGD mice continued to show
      structural and glucocorticoid secretion abnormalities resulting in a late
      response to the environmental change. Thus, our study indicates that PGD
      manipulations affect adrenal development, result in structural and functional
      abnormalities of the adrenals in the offspring and influence their reactivity and
      adaptability to cold stress. 

PMID- 24104562
TI  - Salvage treatment of trigeminal neuralgia by occipital nerve stimulation.
AB  - BACKGROUND: Although most patients suffering from trigeminal neuralgia (TN)
      respond to medical or surgical treatment, nonresponders remain in very severe
      painful condition. CASE RESULT: We describe for the first time a case of severe
      refractory classical TN treated successfully (follow-up one year) by chronic
      bilateral occipital nerve stimulation (ONS), because other classic medical and
      surgical options failed or could not be performed. CONCLUSIONS: This single case
      suggests that ONS might be offered to TN patients refractory both to standard
      drugs and interventions, with a favorable risk/benefit ratio, although its long
      term efficacy remains unknown.

PMID- 24104564
TI  - In vivo intracellular pH measurements in tobacco and Arabidopsis reveal an
      unexpected pH gradient in the endomembrane system.
AB  - The pH homeostasis of endomembranes is essential for cellular functions. In order
      to provide direct pH measurements in the endomembrane system lumen, we targeted
      genetically encoded ratiometric pH sensors to the cytosol, the endoplasmic
      reticulum, and the trans-Golgi, or the compartments labeled by the vacuolar
      sorting receptor (VSR), which includes the trans-Golgi network and prevacuoles.
      Using noninvasive live-cell imaging to measure pH, we show that a gradual
      acidification from the endoplasmic reticulum to the lytic vacuole exists, in both
      tobacco (Nicotiana tabacum) epidermal (DeltapH -1.5) and Arabidopsis thaliana
      root cells (DeltapH -2.1). The average pH in VSR compartments was intermediate
      between that of the trans-Golgi and the vacuole. Combining pH measurements with
      in vivo colocalization experiments, we found that the trans-Golgi network had an
      acidic pH of 6.1, while the prevacuole and late prevacuole were both more
      alkaline, with pH of 6.6 and 7.1, respectively. We also showed that endosomal pH,
      and subsequently vacuolar trafficking of soluble proteins, requires both vacuolar
      type H(+) ATPase-dependent acidification as well as proton efflux mediated at
      least by the activity of endosomal sodium/proton NHX-type antiporters. 

PMID- 24104563
TI  - Nanoparticles and their applications in cell and molecular biology.
AB  - Nanoparticles can be engineered with distinctive composition, size, shape, and
      surface chemistry to enable novel techniques in a wide range of biological
      applications. The unique properties of nanoparticles and their behavior in
      biological milieu also enable exciting and integrative approaches to studying
      fundamental biological questions. This review will provide an overview of various
      types of nanoparticles and concepts of targeting nanoparticles. We will also
      discuss the advantages and recent applications of using nanoparticles as tools
      for drug delivery, imaging, sensing, and for the understanding of basic
      biological processes. 

PMID- 24104565
TI  - Reticulate evolution of the rye genome.
AB  - Rye (Secale cereale) is closely related to wheat (Triticum aestivum) and barley
      (Hordeum vulgare). Due to its large genome (~8 Gb) and its regional importance,
      genome analysis of rye has lagged behind other cereals. Here, we established a
      virtual linear gene order model (genome zipper) comprising 22,426 or 72% of the
      detected set of 31,008 rye genes. This was achieved by high-throughput transcript
      mapping, chromosome survey sequencing, and integration of conserved synteny
      information of three sequenced model grass genomes (Brachypodium distachyon, rice
      [Oryza sativa], and sorghum [Sorghum bicolor]). This enabled a genome-wide high
      density comparative analysis of rye/barley/model grass genome synteny. Seventeen
      conserved syntenic linkage blocks making up the rye and barley genomes were
      defined in comparison to model grass genomes. Six major translocations shaped the
      modern rye genome in comparison to a putative Triticeae ancestral genome.
      Strikingly dissimilar conserved syntenic gene content, gene sequence diversity
      signatures, and phylogenetic networks were found for individual rye syntenic
      blocks. This indicates that introgressive hybridizations (diploid or polyploidy
      hybrid speciation) and/or a series of whole-genome or chromosome duplications
      played a role in rye speciation and genome evolution.

PMID- 24104566
TI  - Arabidopsis receptor-like protein30 and receptor-like kinase suppressor of BIR1
      1/EVERSHED mediate innate immunity to necrotrophic fungi.
AB  - Effective plant defense strategies rely in part on the perception of non-self
      determinants, so-called microbe-associated molecular patterns (MAMPs), by
      transmembrane pattern recognition receptors leading to MAMP-triggered immunity.
      Plant resistance against necrotrophic pathogens with a broad host range is
      complex and yet not well understood. Particularly, it is unclear if resistance to
      necrotrophs involves pattern recognition receptors. Here, we partially purified a
      novel proteinaceous elicitor called sclerotinia culture filtrate elicitor1
      (SCFE1) from the necrotrophic fungal pathogen Sclerotinia sclerotiorum that
      induces typical MAMP-triggered immune responses in Arabidopsis thaliana. Analysis
      of natural genetic variation revealed five Arabidopsis accessions (Mt-0, Lov-1,
      Lov-5, Br-0, and Sq-1) that are fully insensitive to the SCFE1-containing
      fraction. We used a forward genetics approach and mapped the locus determining
      SCFE1 sensitivity to receptor-like protein30 (RLP30). We also show that SCFE1
      triggered immune responses engage a signaling pathway dependent on the regulatory
      receptor-like kinases brassinosteroid insensitive1-associated receptor kinase1
      (BAK1) and Suppressor of BIR1-1/evershed (SOBIR1/EVR). Mutants of RLP30, BAK1,
      and SOBIR1 are more susceptible to S. sclerotiorum and the related fungus
      Botrytis cinerea. The presence of an elicitor in S. sclerotiorum evoking MAMP
      triggered immune responses and sensed by RLP30/SOBIR1/BAK1 demonstrates the
      relevance of MAMP-triggered immunity in resistance to necrotrophic fungi.

PMID- 24104567
TI  - Arabidopsis J-protein J20 delivers the first enzyme of the plastidial isoprenoid
      pathway to protein quality control.
AB  - Plastids provide plants with metabolic pathways that are unique among eukaryotes,
      including the methylerythritol 4-phosphate pathway for the production of
      isoprenoids essential for photosynthesis and plant growth. Here, we show that the
      first enzyme of the pathway, deoxyxylulose 5-phosphate synthase (DXS), interacts
      with the J-protein J20 in Arabidopsis thaliana. J-proteins typically act as
      adaptors that provide substrate specificity to heat shock protein 70 (Hsp70), a
      molecular chaperone. Immunoprecipitation experiments showed that J20 and DXS are
      found together in vivo and confirmed the presence of Hsp70 chaperones in DXS
      complexes. Mutants defective in J20 activity accumulated significantly increased
      levels of DXS protein (but no transcripts) and displayed reduced levels of DXS
      enzyme activity, indicating that loss of J20 function causes posttranscriptional
      accumulation of DXS in an inactive form. Furthermore, J20 promotes degradation of
      DXS following a heat shock. Together, our data indicate that J20 might identify
      unfolded or misfolded (damaged) forms of DXS and target them to the Hsp70 system
      for proper folding under normal conditions or degradation upon stress. 

PMID- 24104568
TI  - A 7-deoxyloganetic acid glucosyltransferase contributes a key step in secologanin
      biosynthesis in Madagascar periwinkle.
AB  - Iridoids form a broad and versatile class of biologically active molecules found
      in thousands of plant species. In addition to the many hundreds of iridoids
      occurring in plants, some iridoids, such as secologanin, serve as key building
      blocks in the biosynthesis of thousands of monoterpene indole alkaloids (MIAs)
      and many quinoline alkaloids. This study describes the molecular cloning and
      functional characterization of three iridoid glucosyltransfeases (UDP-sugar
      glycosyltransferase6 [UGT6], UGT7, and UGT8) from Madagascar periwinkle
      (Catharanthus roseus) with remarkably different catalytic efficiencies.
      Biochemical analyses reveal that UGT8 possessed a high catalytic efficiency
      toward its exclusive iridoid substrate, 7-deoxyloganetic acid, making it better
      suited for the biosynthesis of iridoids in periwinkle than the other two iridoid
      glucosyltransfeases. The role of UGT8 in the fourth to last step in secologanin
      biosynthesis was confirmed by virus-induced gene silencing in periwinkle plants,
      which reduced expression of this gene and resulted in a large decline in
      secologanin and MIA accumulation within silenced plants. Localization studies of
      UGT8 using a carborundum abrasion method for RNA extraction show that its
      expression occurs preferentially within periwinkle leaves rather than in
      epidermal cells, and in situ hybridization studies confirm that UGT8 is
      preferentially expressed in internal phloem associated parenchyma cells of
      periwinkle species.

PMID- 24104570
TI  - Efficiency and loss mechanisms of plasmonic Luminescent Solar Concentrators.
AB  - Using a hybrid nanoscale/macroscale model, we simulate the efficiency of a
      luminescent solar concentrator (LSC) which employs silver nanoparticles to
      enhance the dye absorption and scatter the incoming light. We show that the
      normalized optical efficiency can be increased from 10.4% for a single dye LSC to
      32.6% for a plasmonic LSC with silver spheres immersed inside a thin dye layer.
      Most of the efficiency enhancement is due to scattering of the particles and not
      due to dye absorption/re-emission. 

PMID- 24104571
TI  - A bioinspired solution for spectrally selective thermochromic VO2 coated
      intelligent glazing.
AB  - We present a novel approach towards achieving high visible transmittance for
      vanadium dioxide (VO(2)) coated surfaces whilst maintaining the solar energy
      transmittance modulation required for smart-window applications. Our method
      deviates from conventional approaches and utilizes subwavelength surface
      structures, based upon those present on the eyeballs of moths, that are
      engineered to exhibit broadband, polarization insensitive and wide-angle
      antireflection properties. The moth-eye functionalised surface is expected to
      benefit from simultaneous super-hydrophobic properties that enable the window to
      self-clean. We develop a set of design rules for the moth-eye surface
      nanostructures and, following this, numerically optimize their dimensions using
      parameter search algorithms implemented through a series of Finite Difference
      Time Domain (FDTD) simulations. We select six high-performing cases for
      presentation, all of which have a periodicity of 130 nm and aspect ratios between
      1.9 and 8.8. Based upon our calculations the selected cases modulate the solar
      energy transmittance by as much as 23.1% whilst maintaining high visible
      transmittance of up to 70.3%. The performance metrics of the windows presented in
      this paper are the highest calculated for VO(2) based smart-windows.

PMID- 24104569
TI  - Morphine biosynthesis in opium poppy involves two cell types: sieve elements and
      laticifers.
AB  - Immunofluorescence labeling and shotgun proteomics were used to establish the
      cell type-specific localization of morphine biosynthesis in opium poppy (Papaver
      somniferum). Polyclonal antibodies for each of six enzymes involved in converting
      (R)-reticuline to morphine detected corresponding antigens in sieve elements of
      the phloem, as described previously for all upstream enzymes transforming (S)
      norcoclaurine to (S)-reticuline. Validated shotgun proteomics performed on whole
      stem and latex total protein extracts generated 2031 and 830 distinct protein
      families, respectively. Proteins corresponding to nine morphine biosynthetic
      enzymes were represented in the whole stem, whereas only four of the final five
      pathway enzymes were detected in the latex. Salutaridine synthase was detected in
      the whole stem, but not in the latex subproteome. The final three enzymes
      converting thebaine to morphine were among the most abundant active latex
      proteins despite a limited occurrence in laticifers suggested by
      immunofluorescence labeling. Multiple charge isoforms of two key O-demethylases
      in the latex were revealed by two-dimensional immunoblot analysis. Salutaridine
      biosynthesis appears to occur only in sieve elements, whereas conversion of
      thebaine to morphine is predominant in adjacent laticifers, which contain
      morphine-rich latex. Complementary use of immunofluorescence labeling and shotgun
      proteomics has substantially resolved the cellular localization of morphine
      biosynthesis in opium poppy. 

PMID- 24104572
TI  - Polarized white light from LEDs using remote-phosphor layer sandwiched between
      reflective polarizer and light-recycling dichroic filter.
AB  - This study introduces an efficient polarized, white phosphor-converted, light
      emitting diode (pc-LED) using a remote phosphor film sandwiched between a
      reflective polarizer film (RPF) and a short-wavelength pass dichroic filter
      (SPDF). The on-axis brightness of polarized white light emission of a RPF/SPDF
      sandwiched phosphor film over a blue LED, showed greater recovery than that of a
      conventional unpolarized remote phosphor film over blue LED, due to the recycling
      effect of yellow light from an SPDF. The relative luminous efficacy of an
      RPF/SPDF-sandwiched phosphor film was made 1.40 times better by adding an SPDF on
      the backside of an RPF-capped phosphor film. A polarization ratio of 0.84 was
      demonstrated for a white LED with an RPF/SPDF-sandwiched phosphor film, in good
      agreement with the measured results from the RPF-only sample. 

PMID- 24104573
TI  - Diffractive coupling and plasmon-enhanced photocurrent generation in silicon.
AB  - Arrays of metal nanoparticles are considered candidates for improved light
      coupling into silicon. In periodic arrays the coherent diffractive coupling of
      particles can have a large impact on the resonant properties of the particles. We
      have investigated the photocurrent enhancement properties of Al nanoparticles
      placed on top of a silicon diode in periodic as well as in random arrays. The
      photocurrent of the periodic array sample is enhanced relative to that of the
      random array due to the presence of a Fano-like resonance not observed for the
      random array. Measurements of the photocurrent as a function of angle, reveal
      that the Fano-like enhancement is caused by diffractive coupling in the periodic
      array, which is accordingly identified as an important design parameter for
      plasmon-enhanced light-coupling into silicon. 

PMID- 24104574
TI  - Plasmonic silicon solar cells: impact of material quality and geometry.
AB  - We study n-i-p amorphous silicon solar cells with light-scattering nanoparticles
      in the back reflector. In one configuration, the particles are fully embedded in
      the zinc oxide buffer layer; In a second configuration, the particles are placed
      between the buffer layer and the flat back electrode. We use stencil lithography
      to produce the same periodic arrangement of the particles and we use the same
      solar cell structure on top, thus establishing a fair comparison between a novel
      plasmonic concept and its more traditional counterpart. Both approaches show
      strong resonances around 700 nm in the external quantum efficiency the position
      and intensity of which vary strongly with the nanoparticle shape. Moreover,
      disagreement between simulations and our experimental results suggests that the
      dielectric data of bulk silver do not correctly represent the reality. A better
      fit is obtained by introducing a porous interfacial layer between the silver and
      zinc oxide. Without the interfacial layer, e.g. by improved processing of the
      nanoparticles, our simulations show that the nanoparticles concept could
      outperform traditional back reflectors. 

PMID- 24104575
TI  - Effect of surface type on structural and optical properties of Ag nanoparticles
      formed by dewetting.
AB  - Integration of an array of Ag nanoparticles in solar cells is expected to
      increase light trapping through field enhancement and plasmonic scattering.
      Requirement of Ag nanoparticle decoration of cell surfaces or interfaces at the
      macro-scale, calls for a self-organized fabrication method such as thermal
      dewetting. Optical properties of a 2D array of Ag nanoparticles are known to be
      very sensitive to their shape and size. We show that these parameters depend on
      the type of the substrate used. We observe that the average nanoparticle size
      decreases with increasing substrate thermal conductivity and nanoparticle size
      distribution broadens with increasing surface roughness. 

PMID- 24104576
TI  - Light trapping in thin-film solar cells with randomly rough and hybrid textures.
AB  - We study light-trapping in thin-film silicon solar cells with rough interfaces.
      We consider solar cells made of different materials (c-Si and MUc-Si) to
      investigate the role of size and nature (direct/indirect) of the energy band gap
      in light trapping. By means of rigorous calculations we demonstrate that the
      Lambertian Limit of absorption can be obtained in a structure with an optimized
      rough interface. We gain insight into the light trapping mechanisms by analysing
      the optical properties of rough interfaces in terms of Angular Intensity
      Distribution (AID) and haze. Finally, we show the benefits of merging ordered and
      disordered photonic structures for light trapping by studying a hybrid interface,
      which is a combination of a rough interface and a diffraction grating. This
      approach gives a significant absorption enhancement for a roughness with a modest
      size of spatial features, assuring good electrical properties of the interface.
      All the structures presented in this work are compatible with present-day
      technologies, giving recent progress in fabrication of thin monocrystalline
      silicon films and nanoimprint lithography. 

PMID- 24104577
TI  - Single-material zinc sulfide bi-layer antireflection coatings for GaAs solar
      cells.
AB  - We demonstrated the efficiency improvement of GaAs single-junction (SJ) solar
      cells with the single-material zinc sulfide (ZnS) bi-layer based on the
      porous/dense film structure, which was fabricated by the glancing angle
      deposition (GLAD) method, as an antireflection (AR) coating layer. The porous ZnS
      film with a low refractive index was formed at a high incident vapor flux angle
      of 80 degrees  in the GLAD. Each optimum thickness of ZnS bi-layer was determined
      by achieving the lowest solar weighted reflectance (SWR) using a rigorous coupled
      wave analysis method in the wavelength region of 350-900 nm, extracting the
      thicknesses of 20 and 50 nm for dense and porous films, respectively. The ZnS bi
      layer with a low SWR of ~5.8% considerably increased the short circuit current
      density (J(sc)) of the GaAs SJ solar cell to 25.57 mA/cm(2), which leads to a
      larger conversion efficiency (eta) of 20.61% compared to the conventional one
      without AR layer (i.e., SWR~31%, J(sc) = 18.81 mA/cm(2), and eta = 14.82%).
      Furthermore, after the encapsulation, its J(sc) and eta values were slightly
      increased to 25.67 mA/cm(2) and 20.71%, respectively. For the fabricated solar
      cells, angle-dependent reflectance properties and external quantum efficiency
      were also studied.

PMID- 24104578
TI  - Multiphoton near-infrared quantum cutting luminescence phenomena of Tm3+ ion in
      (Y1-xTm(x))3Al5O12 powder phosphor.
AB  - In the present study, the multiphoton near-infrared downconversion quantum
      cutting luminescence phenomena of Tm3+ ion in (Y(1-x)Tm(x))(3)Al(5)O(12) powder
      phosphor, which is currently a hot research topic throughout the world, is
      reported. The x-ray diffraction spectra, the visible to near-infrared excitation
      and emission spectra, and fluorescence lifetimes are measured. It is found that
      Tm:YAG powder phosphor has intense two-photon quantum cutting luminescence, and,
      for the first time, it is found that Tm:YAG powder phosphor has strong four
      photon near-infrared quantum cutting luminescence of 1788 nm (3)F4 -> (3)H6
      fluorescence of Tm(3+) ion. It is also found that the theoretical up-limit of
      four-photon near-infrared quantum cutting efficiency is about 282.12%, which
      results from both the {(1)D2 -> (3)F2, (3)H6 -> (3)H4} and {(3)H4 -> (3)F4, (3)H6
      -> (3)F4} cross-energy transfers.

PMID- 24104579
TI  - Nano-photonic light trapping near the Lambertian limit in organic solar cell
      architectures.
AB  - A critical step to achieving higher efficiency solar cells is the broad band
      harvesting of solar photons. Although considerable progress has recently been
      achieved in improving the power conversion efficiency of organic solar cells,
      these cells still do not absorb upto ~50% of the solar spectrum. We have designed
      and developed an organic solar cell architecture that can boost the absorption of
      photons by 40% and the photo-current by 50% for organic P3HT-PCBM absorber layers
      of typical device thicknesses. Our solar cell architecture is based on all layers
      of the solar cell being patterned in a conformal two-dimensionally periodic
      photonic crystal architecture. This results in very strong diffraction of photons
      that increases the photon path length in the absorber layer, and plasmonic light
      concentration near the patterned organic-metal cathode interface. The absorption
      approaches the Lambertian limit. The simulations utilize a rigorous scattering
      matrix approach and provide bounds of the fundamental limits of nano-photonic
      light absorption in periodically textured organic solar cells. This solar cell
      architecture has the potential to increase the power conversion efficiency to 10%
      for single band gap organic solar cells utilizing long-wavelength absorbers. 

PMID- 24104580
TI  - Morphology-dependent light trapping in thin-film organic solar cells.
AB  - The active layer materials used in organic photovoltaic (OPV) cells often self
      assemble into highly ordered morphologies, resulting in significant optical
      anisotropies. However, the impact of these anisotropies on light trapping in
      nanophotonic OPV architectures has not been considered. In this paper, we show
      that optical anisotropies in a canonical OPV material, P3HT, strongly affect
      absorption enhancements in ultra-thin textured OPV cells. In particular we show
      that plasmonic and gap-mode solar cell architectures redistribute electromagnetic
      energy into the out-of-plane field component, independent of the active layer
      orientation. Using analytical and numerical calculations, we demonstrate how the
      absorption in these solar cell designs can be significantly increased by
      reorienting polymer domains such that strongly absorbing axes align with the
      direction of maximum field enhancement. 

PMID- 24104581
TI  - Dual-wavelength GaN-based LEDs grown on truncated hexagonal pyramids formed by
      selective-area regrowth on Si-implanted GaN templates.
AB  - GaN-based blue light-emitting diodes (LEDs) with micro truncated hexagonal
      pyramid (THP) array were grown on selective-area Si-implanted GaN (SIG)
      templates. The GaN epitaxial layer regrown on the SIG templates exhibited
      selective growth and subsequent lateral growth to form the THP array. The
      observed selective-area growth was attributed to the different crystal structures
      between the Si-implanted and implantation-free regions. Consequently, LEDs grown
      on the GaN THP array emitted broad electroluminescence spectra with multiple
      peaks. Spatially resolved cathodoluminescence revealed that the broad spectra
      originated from different areas within each THP. Transmission electron microscopy
      showed the GaN-based epitaxial layers, including InGaN/GaN multi-quantum wells
      regrown at different growth rates (or with different In content in the InGaN
      wells) between the semi-polar and c-face planes of each THP. 

PMID- 24104582
TI  - Experimental broadband absorption enhancement in silicon nanohole structures with
      optimized complex unit cells.
AB  - We design silicon membranes with nanohole structures with optimized complex unit
      cells that maximize broadband absorption. We fabricate the optimized design and
      measure the optical absorption. We demonstrate an experimental broadband
      absorption about 3.5 times higher than an equally-thick thin film. 

PMID- 24104583
TI  - Increased upconversion quantum yield in photonic structures due to local field
      enhancement and modification of the local density of states--a simulation-based
      analysis.
AB  - In upconversion processes, two or more low-energy photons are converted into one
      higher-energy photon. Besides other applications, upconversion has the potential
      to decrease sub-band-gap losses in silicon solar cells. Unfortunately,
      upconverting materials known today show quantum yields, which are too low for
      this application. In order to improve the upconversion quantum yield, two
      parameters can be tuned using photonic structures: first, the irradiance can be
      increased within the structure. This is beneficial, as upconversion is a non
      linear process. Second, the rates of the radiative transitions between ionic
      states within the upconverter material can be altered due to a varied local
      density of photonic states. In this paper, we present a theoretical model of the
      impact of a photonic structure on upconversion and test this model in a
      simulation based analysis of the upconverter material beta -NaYF(4):20% Er(3+)
      within a dielectric waveguide structure. The simulation combines a finite
      difference time-domain simulation model that describes the variations of the
      irradiance and the change of the local density of photonic states within a
      photonic structure, with a rate equation model of the upconversion processes. We
      find that averaged over the investigated structure the upconversion luminescence
      is increased by a factor of 3.3, and the upconversion quantum yield can be
      improved in average by a factor of 1.8 compared to the case without the structure
      for an initial irradiance of 200 Wm(-2).

PMID- 24104584
TI  - Surface plasmon-enhanced photoluminescence of DCJTB by using silver nanoparticle
      arrays.
AB  - It is demonstrated that photoluminescence of DCJTB can be enhanced by surface
      plasmons occurred in silver nanoparticle arrays on glass substrates fabricated by
      using nanosphere lithography (NSL) combined with reactive ion etching (RIE). By
      changing the size of the seed polystyrene nanosphere with fixed thickness of
      SiO(2) film as a buffer layer between silver nanoparticles and fluorescent dye,
      we systematically studied the interaction between surface plasmons in Ag
      nanostructures and fluorescent dye by measuring the photoluminescence and time
      resolved photoluminescence (TRPL) of the samples. As compared with pure DCJTB, it
      is observed that PL enhancement as high as 9.4 times and life time shortening
      from 0.966 ns shortened to 0.63 ns can be achieved with polystyrene nanosphere
      430 nm in diameter. The physical origin due to plasmonic excitation has been
      clarified from 3D finite element simulations, as well as the assistance of UV
      visible reflectance spectrum.

PMID- 24104586
TI  - Long-term outcome of abdominal aortic aneurysm repair via a retroperitoneal
      approach.
AB  - BACKGROUND: A retroperitoneal approach for abdominal aortic aneurysm repair has
      demonstrated similar short-term postoperative outcomes compared with the
      transperitoneal approach. However, there is no long-term survival data utilizing
      exclusively open repair via retroperitoneal approach. METHODS: We have conducted
      a retrospective analysis to evaluate the long-term survival of 142 patients with
      infrarenal aortic aneurysm undergoing elective open surgical repair via a
      retroperitoneal approach. RESULTS: Our cohort of patients consisted of 82% males,
      59% whites, and a mean age of 72.6+/-7.7 years. The 30-day mortality rate was
      3.5% for open repair via retroperitoneal approach. Post-operative complications
      were low, with renal failure (9.9%), pulmonary complication (9.9%), and limb
      ischemia (6.3%) being the most prevalent. Five years after surgery, the
      cumulative survival rate was 70.1%. CONCLUSIONS: The elective management of
      infrarenal aortic aneurysms with open repair via a retroperitoneal approach
      offers a good prognosis demonstrated with up to 5 year follow up.

PMID- 24104587
TI  - [No disadvantage of pathogen-reduced platelets?].

PMID- 24104588
TI  - [PICC: higher risk of venous thromboembolism than conventional central venous
      catheters? Definitely more venous thrombosis with PICCs--especially in patients
      at high risk].

PMID- 24104589
TI  - [How safe are dimenhydrinate suppositories?].
AB  - HISTORY: A 13-month-old girl suffered from 3 generalized tonic-clonic seizures
      for several minutes within a total period of 9 hours. History revealed that the
      child received a total of 5 dimenhydrinate containing suppositories a 40 mg
      during the previous 2 days (i. e. 23 mg dimenhydrinate per kg body weight) due to
      enteritis with vomiting. The first seizure occurred 10 hours after the last
      administration. INVESTIGATIONS: The plasma level of diphenhydramin was 230 ug/l
      approximately one hour after the first seizure. Electroencephalography showed no
      pathological signs, an MRI scan of the brain was normal except of several small
      gliotic spots and body temperature was regularly. TREATMENT AND COURSE: Two
      stationary occurring seizures were stopped with 5 mg diazepam rectally. Continued
      surveillance and an EEG two days later showed age-appropriate normal findings.
      There were no further seizures in the next 4 years. CONCLUSION: Infants have the
      risk to develop dimenhydrinate intoxication, especially in cases where
      suppositories were given repeatedly because of intermittent defecation.

PMID- 24104590
TI  - [49-year-old patient with acute abdominal pain. Acute colonic pseudo
      obstruction].

PMID- 24104591
TI  - [Chronic lymphocytic leukemia].
AB  - Chronic lymphocytic leukemia (CLL) is a lymphoproliferative disorder that
      accounts for approximately 30 % of adult leukemias and 25 % of Non-Hodgkin
      lymphomas (NHL). It is the most common form of leukemia in the western world
      (incidence 3-5/100 000). Elderly people are mainly affected, median age at
      diagnosis is around 70 years and there is a slight predominance in men. The
      etiology of the disease is unknown. The initial symptoms are nonspecific.
      Cervical lymphadenopathy and splenomegaly followed by general fatigue are seen
      most commonly. Other possible symptoms include night sweats, fever, loss of
      weight (so-called B symptoms) and frequent infections. Several patients develop
      autoimmune complications as autoimmune hemolytic anemia (AIHA) or immune
      thrombocytopenia (ITP). To confirm the diagnosis more than 5000 B-lymphocytes/ul
      need to be present. The expression of the typical surface markers CD5, CD19, and
      CD23 has to be confirmed by flow cytometry. Imaging studies as X-ray of the
      chest, ultrasound of the abdomen, or CT scan are used to assess the degree of
      lymphadenopathy or organomegaly. A bone marrow biopsy is not mandatory for the
      diagnosis. According to the European Binet staging system, CLL is divided into 3
      stages (A, B and C). Patients in Binet stage A have 0 to 2 areas of node or organ
      enlargement with normal levels of hemoglobin and platelets. Binet stage B
      patients have 3 to 5 areas of node or organ enlargement and normal or slightly
      decreased levels of hemoglobin and platelets. Binet stage C patients have anemia
      (hemoglobin < 10 g/dl) and/or thrombocytopenia (platelet counts < 100 000/ul),
      with or without lymphadenopathy or organomegaly. As there is no survival benefit
      associated with early intervention, asymptomatic patients with early stage CLL
      (Binet stage A and B) are usually not treated but are followed on a "watch and
      wait" principle. Treatment indications include stage Binet C or signs of an
      active disease as rapidly progressive lymphadenopathy or organomegaly together
      with physical limitation, B symptoms that cannot be tolerated, rapidly
      deteriorating blood values, or rapidly increasing leukocyte counts. The patient's
      physical condition has major impact on the treatment decision. Currently
      immunochemotherapy with fludarabine, cyclophosphamide and the CD20-antibody
      rituximab (FCR) is the standard of care in previously untreated and physically
      fit CLL-patients. An alternative regimen is the combination of bendamustine and
      rituximab (BR). Physically compromised patients can be treated with the oral drug
      chlorambucil or with bendamustine with or without rituximab. Due to high
      morbidity and mortality, allogeneic stem cell transplantation is limited to a
      small group of patients and should be discussed in a high-risk situation, such as
      17p deletion, lack of response to standard therapy or early relapse.

PMID- 24104592
TI  - First imaging results of an intraindividual comparison of (11)C-acetate and (18)F
      fluorocholine PET/CT in patients with prostate cancer at early biochemical first
      or second relapse after prostatectomy or radiotherapy.
AB  - PURPOSE: (18)F-Fluorocholine (FCH) and (11)C-acetate (ACE) PET are widely used
      for detection of recurrent prostate cancer (PC). We present the first results of
      a comparative, prospective PET/CT study of both tracers evaluated in the same
      patients presenting with recurrence and low PSA to compare the diagnostic
      information provided by the two tracers. METHODS: The study group comprised 23
      patients studied for a rising PSA level after radical prostatectomy (RP, 7
      patients, PSA <= 3 ng/ml), curative radiotherapy (RT, 7 patients, PSA <= 5 ng/ml)
      or RP and salvage RT (9 patients, PSA <= 5 ng/ml). Both FCH and ACE PET/CT scans
      were performed in a random sequence a median of 4 days (range 0 to 11 days)
      apart. FCH PET/CT was started at injection (307 +/- 16 MBq) with a 10-min dynamic
      acquisition of the prostate bed, followed by a whole-body PET scan and late (45
      min) imaging of the pelvis. ACE PET/CT was performed as a double whole-body PET
      scan starting 5 and 22 min after injection (994 +/- 72 MBq), and a late view (45
      min) of the prostate bed. PET/CT scans were blindly reviewed by two independent
      pairs of two experienced nuclear medicine physicians, discordant subgroup results
      being discussed to reach a consensus for positive, negative end equivocal
      results. RESULTS: PET results were concordant in 88 out of 92 local, regional and
      distant findings (Cohen's kappa 0.929). In particular, results were concordant in
      all patients concerning local status, bone metastases and distant findings. Lymph
      node results were concordant in 19 patients and different in 4 patients. On a per
      patient basis results were concordant in 22 of 23 patients (14 positive, 5
      negative and 3 equivocal). In only one patient was ACE PET/CT positive for nodal
      metastases while FCH PET/CT was overall negative; interestingly, the ACE-positive
      and FCH-negative lymph nodes became positive in a second FCH PET/CT scan
      performed a few months later. CONCLUSION: Overall, ACE and FCH PET/CT showed
      excellent concordance, on both a per-lesion and a per-patient basis, suggesting
      that both tracers perform equally for recurrent prostate cancer staging.

PMID- 24104593
TI  - Area under the cumulative SUV-volume histogram is not a viable metric of
      intratumoral metabolic heterogeneity: further comments.

PMID- 24104596
TI  - Hollow fibers networked with perovskite nanoparticles for H2 production from
      heavy oil.
AB  - Design of catalytic materials has been highlighted to build ultraclean use of
      heavy oil including liquid-to-gas technology to directly convert heavy
      hydrocarbons into H2-rich gas fuels. If the H2 is produced from such heavy oil
      through high-active and durable catalysts in reforming process that is being
      constructed in hydrogen infrastructure, it will be addressed into renewable
      energy systems. Herein, the three different hollow fiber catalysts networked with
      perovskite nanoparticles, LaCr(0.8)Ru(0.2)O3, LaCr(0.8)Ru(0.1)Ni(0.1)O3, and
      LaCr(0.8)Ni(0.2)O3 were prepared by using activated carbon fiber as a sacrificial
      template for H2 production from heavy gas oil reforming. The most important
      findings were arrived at: (i) catalysts had hollow fibrous architectures with
      well-crystallized structures, (ii) hollow fibers had a high specific surface area
      with a particle size of ~50 nm, and (iii) the Ru substituted ones showed high
      efficiency for H2 production with substantial durability under high
      concentrations of S, N, and aromatic compounds.

PMID- 24104595
TI  - Gene regulatory network of renal primordium development.
AB  - Animal development progresses through the stepwise deployment of gene regulatory
      networks (GRN) encoded in the genome. Comparative analyses in different species
      and organ systems have revealed that GRN blueprints are composed of subcircuits
      with stereotypical architectures that are often reused as modular units. In this
      review, we report the evidence for the GRN underlying renal primordium
      development. In vertebrates, renal development is initiated by the induction of a
      field of intermediate mesoderm cells competent to undergo lineage specification
      and nephric (Wolffian) duct formation. Definition of the renal field leads to the
      activation of a core regulatory subcircuit composed of the transcription factors
      Pax2/8, Gata3 and Lim1. These transcription factors turn on a second layer of
      transcriptional regulators while also activating effectors of tissue
      morphogenesis and cellular specialization. Elongation and connection of the
      nephric duct to the cloaca (bladder/urethra primordium) is followed by
      metanephric kidney induction through signals emanating from the metanephric
      mesenchyme. Central to this process is the activation and positioning of the
      glial cell line-derived neurotrophic factor (Gdnf)-Ret signaling pathway by
      network subcircuits located in the mesenchyme and epithelial tissues of the
      caudal trunk. Evidence shows that each step of the renal primordium developmental
      program is regulated by structured GRN subunits organized in a hierarchical
      manner. Understanding the structure and dynamics of the renal GRN will help us
      understand the intrinsic phenotypical variability of congenital anomalies of the
      kidney and urinary tract and guide our approaches to regenerative medicine. 

PMID- 24104594
TI  - Epigenetics, autism spectrum, and neurodevelopmental disorders.
AB  - Epigenetic marks are modifications of DNA and histones. They are considered to be
      permanent within a single cell during development, and are heritable across cell
      division. Programming of neurons through epigenetic mechanisms is believed to be
      critical in neural development. Disruption or alteration in this process causes
      an array of neurodevelopmental disorders, including autism spectrum disorders
      (ASDs). Recent studies have provided evidence for an altered epigenetic landscape
      in ASDs and demonstrated the central role of epigenetic mechanisms in their
      pathogenesis. Many of the genes linked to the ASDs encode proteins that are
      involved in transcriptional regulation and chromatin remodeling. In this review
      we highlight selected neurodevelopmental disorders in which epigenetic
      dysregulation plays an important role. These include Rett syndrome, fragile X
      syndrome, Prader-Willi syndrome, Angelman syndrome, and Kabuki syndrome. For each
      of these disorders, we discuss how advances in our understanding of epigenetic
      mechanisms may lead to novel therapeutic approaches. 

PMID- 24104597
TI  - Outcome of adolescents and young adults with acute myeloid leukemia treated on
      COG trials compared to CALGB and SWOG trials.
AB  - BACKGROUND: A retrospective meta-analysis of adolescents and young adults (AYAs)
      with acute myeloid leukemia (AML) was performed to determine if differences in
      outcome exist following treatment on pediatric versus adult oncology treatment
      regimens. METHODS: Outcomes were compared of 517 AYAs with AML aged 16 to 21
      years who were treated on Children's Oncology Group (COG), Cancer and Leukemia
      Group B (CALGB), and Southwest Oncology Group (SWOG) frontline AML trials from
      1986 to 2008. RESULTS: There was a significant age difference between AYA cohorts
      in the COG, CALGB, and SWOG trials (median, 17.2 versus 20.1 versus 19.8 years, P
      < .001). The 10-year event-free survival of the COG cohort was superior to the
      combined adult cohorts (38% +/- 6% versus 23% +/- 6%, log-rank P = .006) as was
      overall survival (45% +/- 6% versus 34% +/- 7%), with a 10-year estimate
      comparison of P = .026. However, the younger age of the COG cohort is
      confounding, with all patients aged 16 to 18 years doing better than those aged
      19 to 21 years. Although the 10-year relapse rate was lower for the COG patients
      (29% +/- 6% versus 57% +/- 8%, Gray's P < .001), this was offset by a higher
      postremission treatment-related mortality of 26% +/- 6% versus 12% +/- 6% (Gray's
      P < .001). Significant improvements in 10-year event-free survival and overall
      survival were observed for the entire cohort in later studies. CONCLUSIONS:
      Patients treated on pediatric trials had better outcomes than those treated on
      adult trials, but age is a major confounding variable, making it difficult to
      compare outcomes by cooperative group.

PMID- 24104598
TI  - Decoupling of QT interval variability from heart rate variability with ageing.
AB  - Ageing has been associated with changes in cardiac electrophysiology that result
      in QT interval prolongation. The effect of age on rate-adaptation dynamics of the
      QT interval is less well understood. The aim of this study was to assess age
      related changes in the temporal relationship between QT and RR interval
      variability. Resting ECG of 20 young and 20 elderly healthy subjects were
      analyzed. Beat-to-beat RR and QT interval time series were automatically
      extracted. Coupling between QT and RR was assessed by means of the QT variability
      index, coherence in the frequency domain, rate-corrected QT interval, cross
      multiscale entropy, information based similarity index and joint symbolic
      dynamics. In addition to QT interval prolongation (433 +/- 31 versus 405 +/- 33
      ms, p = 0.008), elderly subjects were characterized by a significantly increased
      QT variability index (-1.26 +/- 0.28 versus -1.52 +/- 0.22 ms, p < 0.0001),
      reduced coherence in high (0.11 +/- 0.09 versus 0.29 +/- 0.14 ms, p = 0.003), and
      low frequency bands (0.20 +/- 0.16 versus 0.49 +/- 0.15 ms, p < 0.0001), reduced
      information domain synchronization index (0.13 +/- 0.07 versus 0.19 +/- 0.05 ms,
      p = 0.001) as well as increased entropy and disparity in joint symbolic dynamics
      of QT and RR interval time series. In conclusion, ageing is associated with
      decoupling of QT variability from heart rate variability. Complexity analysis in
      addition to standard metrics may provide additional insight. 

PMID- 24104601
TI  - Variations in serum TARC and I-TAC levels reflect minor changes in disease
      activity and pruritus in atopic dermatitis.

PMID- 24104599
TI  - Efficient gene delivery to pig airway epithelia and submucosal glands using
      helper-dependent adenoviral vectors.
AB  - Airway gene delivery is a promising strategy to treat patients with life
      threatening lung diseases such as cystic fibrosis (CF). However, this strategy
      has to be evaluated in large animal preclinical studies in order to translate it
      to human applications. Because of anatomic and physiological similarities between
      the human and pig lungs, we utilized pig as a large animal model to examine the
      safety and efficiency of airway gene delivery with helper-dependent adenoviral
      vectors. Helper-dependent vectors carrying human CFTR or reporter gene LacZ were
      aerosolized intratracheally into pigs under bronchoscopic guidance. We found that
      the LacZ reporter and hCFTR transgene products were efficiently expressed in lung
      airway epithelial cells. The transgene vectors with this delivery can also reach
      to submucosal glands. Moreover, the hCFTR transgene protein localized to the
      apical membrane of both ciliated and nonciliated epithelial cells, mirroring the
      location of wild-type CF transmembrane conductance regulator (CFTR). Aerosol
      delivery procedure was well tolerated by pigs without showing systemic toxicity
      based on the limited number of pigs tested. These results provide important
      insights into developing clinical strategies for human CF lung gene
      therapy.Molecular Therapy-Nucleic Acids (2013) 2, e127; doi:10.1038/mtna.2013.55;
      published online 8 October 2013. 

PMID- 24104602
TI  - Significance of Arg3, Arg54, and Tyr58 of L-aspartate alpha-decarboxylase from
      Corynebacterium glutamicum in the process of self-cleavage.
AB  - PURPOSE OF WORK: We have elucidated the significance of three key amino acid
      residues of L-aspartate alpha-decarboxylase that act remotely from its cleavage
      site for its functional self-cleavage as well as for its catalytic activity.
      These results provide useful fundamental information for engineering L-aspartate
      alpha-decarboxylase. L-Aspartate alpha-decarboxylase (ADC) from Corynebacterium
      glutamicum, and encoded by panD, was cloned and expressed in Escherichia coli and
      then purified. Three amino acid residues were found to be related to ADC self
      cleavage. Mutating R3 to either A, Q, N, L, D, or E produced only the unprocessed
      pro-enzyme. Although mutating R54 and Y58 into A or K and A or T, respectively,
      partly influenced ADC self-cleavage, the specific activity of each of the four
      betamutants decreased to 3.5, 4, 2.4, and 2.6 U mg(-1), respectively, compared
      with a specific activity of 690 U mg(-1) for the wild-type enzyme. Thus, R3
      triggers ADC self-cleavage and completes the modification of the active site with
      assistance by R54 and Y58. These results will help to engineer ADC for improved
      industrial applications.

PMID- 24104603
TI  - Electrofluidics fabricated by space-selective metallization in glass microfluidic
      structures using femtosecond laser direct writing.
AB  - Space-selective metallization of the inside of glass microfluidic structures
      using femtosecond laser direct-write ablation followed by electroless plating is
      demonstrated. Femtosecond laser direct writing followed by thermal treatment and
      successive chemical etching allows us to fabricate three-dimensional microfluidic
      structures inside photosensitive glass. Then, femtosecond laser ablation followed
      by electroless metal plating enables flexible deposition of patterned metal films
      on desired locations of not only the top and bottom walls but also the sidewalls
      of fabricated microfluidic structures. A volume writing scheme for femtosecond
      laser irradiation inducing homogeneous ablation on the sidewalls of microfluidic
      structures is proposed for sidewall metallization. The developed technique is
      used to fabricate electrofluidics in which microelectric components are
      integrated into glass microchannels. The fabricated electrofluidics are applied
      to control the temperature of liquid samples in the microchannels for the
      enhancement of chemical reactions and to manipulate the movement of biological
      samples in the microscale space. 

PMID- 24104604
TI  - Critical review of complementary and alternative medicine use in menopause: focus
      on prevalence, motivation, decision-making, and communication.
AB  - OBJECTIVE: This study aims to undertake the first critical review of
      complementary and alternative medicine (CAM) use among menopausal women (a term
      here used to include premenopausal, perimenopausal and postmenopausal women) by
      focusing on the prevalence of CAM use and CAM users' characteristics, motivation,
      decision-making, and communication with healthcare providers. METHODS: A
      comprehensive search of 2002-2012 international literature in the Medline,
      CINAHL, AMED, and SCOPUS databases was conducted. The search was confined to peer
      reviewed articles published in English with abstracts and reporting new empirical
      research findings regarding CAM use and menopause. RESULTS: A considerable level
      of CAM use was observed among women in menopause. Many menopausal women use CAM
      concurrently with their conventional medicine. However, communication regarding
      CAM between menopausal women and healthcare providers seems less than optimal,
      with a demand for further information on the safety and efficacy of medicines.
      Existing literature is of variable methodological rigor, often presenting small
      sample sizes and low-quality data collection. Further rigorous research on this
      topic-including quantitative and qualitative methods using large national
      samples, where relevant-is required. CONCLUSIONS: The findings of this critical
      review provide insights for those practicing and managing health care in this
      area of women's health. Healthcare providers should prepare to inform menopausal
      women about all treatment options, including CAM, and should be aware of the
      possible adverse effects of CAM and potential interactions between CAM and
      conventional medicine among women in menopause who are under their care.

PMID- 24104605
TI  - Menopausal medicine: how to educate the next generation of menopause clinicians.

PMID- 24104607
TI  - Issues of affinity: exploring population structure in the Middle and Regional
      Developments Periods of San Pedro de Atacama, Chile.
AB  - The Middle Period (AD 400-1000) in northern Chile's Atacama oases is
      characterized by an increase in social complexity and regional interaction, much
      of which was organized around the power and impact of the Tiwanaku polity.
      Despite the strong cultural influence of Tiwanaku and numerous other groups
      evident in interactions with Atacamenos, the role of immigration into the oases
      during this period is unclear. While archaeological and bioarchaeological
      research in the region has shown no evidence that clearly indicates large groups
      of foreign immigrants, the contemporary increase in interregional exchange
      networks connecting the oases to other parts of the Andes suggests residential
      mobility and the possibility that movement of people both into and out of the
      oases accompanied these foreign influences. Here, we analyze biodistance through
      cranial non-metric traits in a skeletal sample from prehistoric San Pedro de
      Atacama to elucidate the extent of foreign influence in the oases and discuss its
      implications. We analyzed 715 individuals from the Middle Period (AD 400-1000)
      and later Regional Developments Period (AD 1000-1450), and found greater
      phenotypic differences between Middle Period cemeteries than among cemeteries in
      the subsequent period. We argue that this greater diversity extends beyond the
      relationship between the oases and the renowned Tiwanaku polity and reflects the
      role of the oases and its different ayllus as a node and way station for the
      Middle Period's myriad interregional networks.

PMID- 24104608
TI  - Synbindin in extracellular signal-regulated protein kinase spatial regulation and
      gastric cancer aggressiveness.
AB  - BACKGROUND: The molecular mechanisms that control the aggressiveness of gastric
      cancer (GC) remain poorly defined. Here we show that synbindin contributes to the
      aggressiveness of GC by activating extracellular signal-regulated protein kinase
      (ERK) signaling on the Golgi apparatus. METHODS: Expression of synbindin was
      examined in normal gastric mucosa (n = 44), intestinal metaplastic gastric mucosa
      (n = 66), and GC tissues (n=52), and the biological effects of synbindin on tumor
      growth and ERK signaling were detected in cultured cells, nude mice, and human
      tissue samples. The interaction between synbindin and mitogen-activated protein
      kinase kinase (MEK1)/ERK was determined by immunofluorescence and fluorescence
      resonance energy transfer assays. The transactivation of synbindin by nuclear
      factor kappa-light-chain-enhancer of activated B cells (NF-kappaB) was detected
      using luciferase reporter assay and chromatin immunoprecipitation. RESULTS: High
      expression of synbindin was associated with larger tumor size (120.8 vs 44.8
      cm(3); P = .01), advanced tumor node metastasis (TNM) stage (P = .003), and
      shorter patient survival (hazard ratio = 1.51; 95% confidence interval [CI] =
      1.01 to 2.27; P = .046). Synbindin promotes cell proliferation and invasion by
      activating ERK2 on the Golgi apparatus, and synbindin is directly transactivated
      by NF-kappaB. Synbindin expression level was statistically significantly higher
      in human GCs with activated ERK2 than those with low ERK2 activity (intensity
      score of 11.5, 95% CI = 10.4 to 12.4 vs intensity score of 4.6, 95% CI 3.9 to
      5.3; P < .001). Targeting synbindin in xenograft tumors decreased ERK2
      phosphorylation and statistically significantly reduced tumor volume (451.2mm(3),
      95% CI = 328.3 to 574.1 vs 726.1mm(3), 95% CI = 544.2 to 908.2; P = .01).
      CONCLUSIONS: Synbindin contributes to malignant phenotypes of GC by activating
      ERK on the Golgi, and synbindin is a potential biomarker and therapeutic target
      for GC.

PMID- 24104609
TI  - Altered GABAA receptor expression and seizure threshold following acute ethanol
      challenge in mice lacking the RIIbeta subunit of PKA.
AB  - Ethanol causes pathological changes in GABAA receptor trafficking and function.
      These changes are mediated in part by ethanol activation of protein kinase A
      (PKA). The current study investigated the expression of the GABAA alpha1 and
      alpha4 subunits and the kinase anchoring protein AKAP150, as well as bicuculline
      induced seizure threshold, at baseline and following acute injection of ethanol
      (3.5 g/kg IP) in a mouse line lacking the regulatory RIIbeta subunit of PKA.
      Whole cerebral cortices were harvested at baseline, 1 h, or 46 h following
      injection of ethanol or saline and subjected to fractionation and western blot
      analysis. Knockout (RIIbeta-/-) mice had similar baseline levels of PKA RIIalpha
      and GABAA alpha1 and alpha4 subunits compared to wild type (RIIbeta+/+)
      littermates, but had deficits in AKAP150. GABAA alpha1 subunit levels were
      decreased in the P2 fraction of RIIbeta-/-, but not RIIbeta+/+, mice following 1
      h ethanol, an effect that was driven by decreased alpha1 expression in the
      synaptic fraction. GABAA alpha4 subunits in the P2 fraction were not affected by
      1 h ethanol; however, synaptic alpha4 subunit expression was increased in
      RIIbeta+/+, but not RIIbeta-/- mice, while extrasynaptic alpha4 and delta subunit
      expression were decreased in RIIbeta-/-, but not RIIbeta+/+ mice. Finally,
      RIIbeta knockout was protective against bicuculline-induced seizure
      susceptibility. Overall, the results suggest that PKA has differential roles in
      regulating GABAA receptor subunits. PKA may protect against ethanol-induced
      deficits in synaptic alpha1 and extrasynaptic alpha4 receptors, but may
      facilitate the increase of synaptic alpha4 receptors. 

PMID- 24104611
TI  - Reply to comment "Comment on Jugun et al.: The safety and efficacy of high-dose
      daptomycin combined with rifampicin for the treatment of Gram-positive
      osteoarticular infections" by Lu et al.

PMID- 24104610
TI  - Localization of mitochondrial carnitine/acylcarnitine translocase in sensory
      neurons from rat dorsal root ganglia.
AB  - The carnitine/acylcarnitine transporter is a transport system whose function is
      essential for the mitochondrial beta-oxidation of fatty acids. Here, the presence
      of carnitine/acylcarnitine carrier (CACT) in nervous tissue and its sub-cellular
      localization in dorsal root ganglia (DRG) neurons have been investigated. Western
      blot analysis using a polyclonal anti-CACT antibody produced in our laboratory
      revealed the presence of CACT in all the nervous tissue extracts analyzed.
      Confocal microscopy experiments performed on fixed and permeabilized DRG neurons
      co-stained with the anti-CACT antibody and the mitochondrial marker MitoTracker
      Red clearly showed a mitochondrial localization for the carnitine/acylcarnitine
      transporter. The transport activity of CACT from DRG extracts reconstituted into
      liposomes was about 50 % in respect to liver extracts. The experimental data here
      reported represent the first direct evidence of the expression of the
      carnitine/acylcarnitine transporter in sensory neurons, thus supporting the
      existence of the beta-oxidation pathway in these cells. 

PMID- 24104612
TI  - Female gender doubles pre-hospital delay times for patients experiencing ST
      segment elevation myocardial infarction in Saudi Arabia.
AB  - INTRODUCTION: Pre-hospital delay has a significant impact on patients' mortality
      and morbidity in ST segment elevation myocardial infarction (STEMI).
      Internationally many factors including female gender have been implicated, but no
      research has been conducted in Arab cultures. We aimed to explore the factors
      contributing to pre-hospital delay among female STEMI patients in Saudi Arabia.
      METHOD: This sequential, explanatory mixed methods study comprised a consecutive
      sample of 311 patients, presenting with STEMI to three hospitals in Riyadh, from
      March 2011-August 2011. Of these, 189 patients (36 females) were eligible and
      interviewed using the Response to Symptoms Questionnaire. A purposive sample of
      18 patients (9 females) then participated in qualitative interviews that were
      taped and transcribed prior to thematic analysis. FINDINGS: The median pre
      hospital delay for males was 5 h and 12.9 h for females (p<0.002). Standard
      multiple regression determined female gender as the strongest predictor of
      transfer delay-from decision to seek help to hospital arrival. Qualitative
      analysis produced five gender-related themes: (a) women require a male relative's
      permission to seek medical help; (b) women cannot travel to hospital unless
      accompanied by a male relative; (c) women prioritise family responsibilities over
      seeking help; (d) women lack knowledge of myocardial infarction (MI) symptoms and
      treatment; and (e) perception that women should not attract attention.
      CONCLUSION: This study provides new insight into how cultural factors increase
      pre-hospital delay for women within Saudi Arabia. While the quantitative data
      demonstrates that women experience much longer delays, the qualitative interviews
      confirm that cultural factors are implicated. Further research is urgently
      required.

PMID- 24104615
TI  - Generation of sub-20-fs deep-ultraviolet pulses by using chirped-pulse four-wave
      mixing in CaF2 plate.
AB  - Sub-20-fs deep ultraviolet (DUV) pulses are generated by using nondegenerate,
      chirped-pulse four-wave mixing of the fundamental and second-harmonic pulses from
      a commercial Ti:sapphire amplifier in a CaF(2) plate. The energy of the DUV
      pulses is 3.8 MUJ, with a conversion efficiency from total pump energy to DUV of
      ~3.8%. The DUV pulse is compressed using a pre-chirp, introduced via a fused
      silica window in the fundamental beam. The central wavelength of the DUV spectrum
      can be tuned from 257 to 277 nm by adjusting the cross angle between the two pump
      beams. The spectrum can reach a width of 16.8 nm, which can support a pulse
      duration of 8.7 fs.

PMID- 24104614
TI  - Evaluation of disparate laser beam deflection technologies by means of number and
      rate of resolvable spots.
AB  - We introduce a method to objectively evaluate systems of differing beam
      deflection technologies that commonly are described by disparate technical
      specifications. Using our new approach based on resolvable spots we will compare
      commercially available random-access beam deflection technologies, namely
      galvanometer scanners, piezo scanners, MEMS scanners, acousto-optic deflectors,
      and electro-optic deflectors. 

PMID- 24104613
TI  - Telephone monitoring of adverse events during an MF59(r)-adjuvanted H5N1
      influenza vaccination campaign in Taiwan.
AB  - This study was conducted to explore a telephone-based approach for identifying
      and quantifying the occurrence of adverse events following immunization (AEFIs)
      during an MF59(r)-adjuvanted H5N1 vaccination program in Taiwan. From March to
      August 2011, each H5N1 vaccine recipient who voluntarily registered as
      participants within 72 h of vaccination was phone interviewed at postvaccination
      7-10 and 21-24 d. Among the 292 participants, 270 and 263 interviews were
      completed at 7-10 and 21-24 d. Overall, 127 (48%) respondents reported local and
      86 (33%) reported systemic reactions. Females (odds ratio [OR] 2.06, 95%
      confidence interval [CI] 1.18-3.63), nonelderly adults aged 18-59 y (OR 3.08, 95%
      CI 1.11-9.45), and first-dose recipients (OR 2.16, 95% CI 1.22-3.86) were
      independently associated with having an AEFI within the first 7-10 d. None of the
      AEFIs reported were serious adverse events. In conclusion, most AEFIs to H5N1
      vaccine were anticipated but varied with sex, age, and vaccine dose number. The
      use of modern information technologies will be a scalable alternative to
      efficiently enroll and monitor recipients with possible AEFIs in large campaigns
      involving influenza or other emerging vaccines. Further studies should compare
      the detection of AEFIs using telephone monitoring and standard pharmacovigilance
      reporting.

PMID- 24104616
TI  - Limits to the representation capacity of imaging in random media.
AB  - The information capacity of an image in the atmosphere, ocean, or biological
      media does not grow indefinitely with increasing light power but has well defined
      limits. Here, the exact effects of the propagation of light in random
      inhomogeneous media are elucidated and upper bounds to the capacity of image
      pixels to represent a corresponding point in the object are described. 

PMID- 24104617
TI  - Self-reconstructing all-optical poling in polymer fibers.
AB  - Self-sustained all-optical poling second-harmonic generation (SHG) experiments
      are conducted in single-core and multicore dye-doped poly(methyl methacrylate)
      optical fibers. By tuning the polarization of the fundamental beam, the SHG
      signal is degraded and is reconstructed spontaneously up to its initial level. We
      found a new situation in which the photo-induced self-organization of azo
      polymers creates a well-ordered periodic structure. 

PMID- 24104618
TI  - Weak-values technique for velocity measurements.
AB  - In a recent Letter, Brunner and Simon proposed an interferometric scheme using
      imaginary weak values with a frequency-domain analysis to outperform standard
      interferometry in longitudinal phase shifts [Phys. Rev. Lett105, 010405 (2010)].
      Here we demonstrate an interferometric scheme combined with a time-domain
      analysis to measure longitudinal velocities. The technique employs the near
      destructive interference of non-Fourier limited pulses, one Doppler shifted due
      to a moving mirror in a Michelson interferometer. We achieve a velocity
      measurement of 400 fm/s and show our estimator to be efficient by reaching its
      Cramer-Rao bound.

PMID- 24104619
TI  - Green-induced blue absorption in MgO-doped lithium niobate crystals.
AB  - We have measured the intrinsic and 532 nm-induced optical absorption of 5 mol. %
      MgO-doped lithium niobate crystals at 488 nm wavelength. The measurements have
      been conducted employing a photothermal common-path interferometer. The
      absorption at 488 nm increases on simultaneous illumination with 532 nm light.
      This induced absorption rises linearly with the stimulating 532 nm radiation
      power and saturates for intensities larger than 50 kW/cm(2). A model developed
      recently, considering the excitation of electrons from levels near the valence
      band into iron centers, is applied to explain the observations.

PMID- 24104620
TI  - Generation of sub-diffraction-limited pure longitudinal magnetization by the
      inverse Faraday effect by tightly focusing an azimuthally polarized vortex beam.
AB  - In this Letter we report on the generation of sub-diffraction-limited pure
      longitudinal magnetization in optomagnetic materials. The interaction between
      polarization singularities of cylindrically polarized beams and optical vortices
      in the tight focus of a high numerical-aperture objective as well as the induced
      magnetic fields through the inverse Faraday effect are investigated. A pure
      longitudinal magnetization distribution throughout the entire focal plane, which
      has a 15% reduction in the lateral full width at half-maximum, is achieved by
      tightly focusing an azimuthally polarized vortex beam. 

PMID- 24104621
TI  - Design trade-offs for silicon-on-insulator-based AWGs for (de)multiplexer
      applications.
AB  - We demonstrate compact silicon-on-insulator-based arrayed waveguide gratings
      (AWGs) for (de)multiplexing applications with a large free spectral range (FSR).
      The large FSR is obtained by reducing the arm aperture pitch without changing the
      device footprint. We demonstrate 4 * 100 GHz, 8 * 250 GHz, and 12 * 400 GHz AWGs
      with FSRs of 6.9, 24.8, and 69.8, respectively. We measured an insertion loss
      from -2.45 dB for high to -0.53 dB for low-resolution AWGs. The crosstalk varies
      between 17.12 and 21.37 dB. The bandwidth remains nearly constant, and the
      nonuniformity between the center wavelength channel and the outer wavelength
      channel improves with larger FSR values.

PMID- 24104622
TI  - Infrared luminescence in bismuth-doped AgCl crystals.
AB  - Experimental and computer-modeling studies of the spectral properties of
      crystalline AgCl doped with metal bismuth or bismuth chloride are performed. The
      broad near-IR luminescence band in the 0.8-1.2 MUm range with time dependence
      described by two exponential components corresponding to the lifetimes of 1.5 and
      10.3 MUs is excited mainly by 0.39-0.44 MUm radiation. Computer modeling of
      probable Bi-related centers in the AgCl lattice is performed. On the basis of
      experimental and calculation data, a conclusion is drawn that IR luminescence can
      be caused by Bi+ ion centers substituted for Ag+ ions.

PMID- 24104623
TI  - Spectrally multiplexed and tunable-wavelength photon pairs at 1.55 MUm from a
      silicon coupled-resonator optical waveguide.
AB  - Using a compact optically pumped silicon nanophotonic chip consisting of coupled
      silicon microrings, we generate photon pairs in multiple pairs of wavelengths
      around 1.55 MUm. The wavelengths are tunable over several nanometers,
      demonstrating the capability to generate wavelength division multiplexed photon
      pairs at freely chosen telecommunications-band wavelengths.

PMID- 24104624
TI  - Spectral dynamics of incoherent waves with a noninstantaneous nonlinear response.
AB  - We study the influence of a constant background noise on the dynamics of spectral
      incoherent solitons, which are incoherent structures sustained by a
      noninstantaneous (Raman-like) nonlinearity. As the level of the noise background
      increases, the incoherent wave enters a novel nonlinear regime characterized by
      oscillatory dynamics of the incoherent spectrum, which develop within a spectral
      cone during the propagation. In contrast to the conventional Raman-like spectral
      red shift, such incoherent spectral dynamics can be characterized by a
      significant spectral blue shift. On the basis of the kinetic wave theory, we
      derive explicit analytical expressions of these incoherent oscillatory spectral
      dynamics. 

PMID- 24104625
TI  - Observation of nitrogen vacancy photoluminescence from an optically levitated
      nanodiamond.
AB  - We present what we believe to be the first evidence of nitrogen vacancy (NV)
      photoluminescence (PL) from a nanodiamond suspended in a free-space optical
      dipole trap at atmospheric pressure. The PL rates are shown to decrease with
      increasing trap laser power, but are inconsistent with a thermal quenching
      process. For a continuous-wave trap, the neutral charge state (NV(0)) appears to
      be suppressed. Chopping the trap laser yields higher total count rates and
      results in a mixture of both NV(0) and the negative charge state (NV(-).

PMID- 24104626
TI  - Fast second-harmonic generation frequency-resolved optical gating using only a
      pulse shaper.
AB  - In many ultrafast contexts, a collinear pulse-shaping frequency-resolved optical
      gating (FROG) technique is desired. Some applicable techniques already exist, but
      they suffer from one of two issues: either they require many time points to allow
      for Fourier filtering, or they do not yield a traditional FROG trace. To overcome
      these issues, we propose and demonstrate a fast new phase-cycled FROG technique
      using a pulse shaper. 

PMID- 24104627
TI  - Combined soliton pulse compression and plasma-related frequency upconversion in
      gas-filled photonic crystal fiber.
AB  - We numerically investigate self-frequency blueshifting of a fundamental soliton
      in a gas-filled hollow-core photonic crystal fiber. Because of the changing
      underlying soliton parameters, the blueshift gives rise to adiabatic soliton
      compression. Based on these features, we propose a device that enables frequency
      shifting over an octave and pulse compression from 30 fs down to 2.3 fs.

PMID- 24104628
TI  - Classical imaging theory of a microlens with super-resolution.
AB  - Super-resolution in imaging through a transparent spherical microlens has
      attracted lots of attention because of recent promising experimental results with
      remarkable resolution improvement. To provide physical insight for this super
      resolution phenomenon, previous studies adopted a phenomenological explanation
      mainly based on the super-focusing effect of a photonic nanojet, while a direct
      imaging calculation with classical imaging theory has rarely been studied. Here
      we theoretically model the imaging process through a microlens with vectorial
      electromagnetic analysis, and then exclude the previously plausible explanation
      of super-resolution based on the super-focusing effect. The results showed that,
      in the context of classical imaging theory subject to the two-point resolution
      criterion, a microlens with a perfect spherical shape cannot achieve the
      experimentally verified sub-100 nm resolution. Therefore, there must be some
      other physical mechanisms that contribute to the reported ultrahigh resolution
      but have not been revealed in theory.

PMID- 24104629
TI  - Improving polarization squeezing in Sagnac interferometer configuration using
      photonic crystal fiber.
AB  - The greater confinement of light that is possible in photonic crystal fibers
      (PCFs) leads to greater effective nonlinearity, which promises to yield greater
      quantum squeezing than is possible in standard optical fiber. However,
      experimental work to date has not achieved improvements over standard fiber. We
      present a comprehensive numerical investigation of polarization squeezing in PCF
      in a Sagnac configuration. By including loss, a noninstantaneous Raman response,
      excess phase-noise, second- and third-order dispersion, and self-steepening, the
      simulations are able to identify the physical factors that limit current PCF
      squeezing experiments. 

PMID- 24104630
TI  - Relation between transmission eigenchannels and single-channel optimizing modes
      in a disordered medium.
AB  - The wave transport through disordered media, although a random process, has some
      universal physical properties. One of these properties that has been investigated
      in this report is the relation between transmission eigenchannels and the so
      called single-channel optimizing mode, which maximizes the intensity of the
      transmitted wave at a single specific output channel. Since single-channel
      optimizing modes have higher transmittance than the uncontrolled waves, it has
      been predicted before that transmission eigenchannels with higher transmittance
      preferentially contribute to the single-channel optimizing modes in proportion to
      the square of eigenvalues. In this Letter, we report the experimental validation
      of this prediction by measuring cross-correlation between the single-channel
      optimizing modes and the transmission eigenchannels. 

PMID- 24104631
TI  - Rapid time-gated polarimetric Stokes imaging using photoelastic modulators.
AB  - We report a rapid time-gated full Stokes imaging approach without mechanically
      moving parts, which is well-suited for biomedical applications, using two
      photoelastic modulators (PEMs). A charge-coupled device (CCD) with microsecond
      time-gating capability was used to acquire the images. To synchronize the CCD
      with the PEMs, thus gaining signal-to-noise ratio advantage, a field programmable
      gate array was employed. After calibration, an evolutionary algorithm was used to
      select four time points from which the full Stokes vector can be recovered. Using
      the images taken by the camera at these four times (in ~80 ms), the images of the
      full Stokes vectors of different incident polarization states were accurately
      derived.

PMID- 24104632
TI  - Integrated optical modulators and switches using coherent perfect loss.
AB  - We propose a new type of amplitude modulator for integrated optics based on phase
      controllable coherent perfect loss (CPL) from a resonant cavity. Temporal coupled
      mode theory is employed to derive a simple set of equations that describe the
      device operation, and finite-difference time-domain simulations are used to
      verify these equations. Two examples of CPL modulators are described with this
      formalism: a ring resonator and a 1D photonic crystal cavity. We show that
      internal resonator loss, and thus critical coupling, are not strict requirements
      for CPL operation. These devices are simple to design and can act as compact
      switches and modulators for integrated optics. 

PMID- 24104633
TI  - Ultracompact and broadband polarization beam splitter utilizing the evanescent
      coupling between a hybrid plasmonic waveguide and a silicon nanowire.
AB  - An ultracompact polarization beam splitter (PBS) is proposed based on an
      asymmetrical directional coupler consisting of a silicon hybrid plasmonic
      waveguide (HPW) and a silicon nanowire. The widths of the two coupling waveguides
      are chosen so that the phase-matching condition is satisfied for TE polarization
      only while the phase mismatch is significant for TM polarization. A sharply bent
      silicon HPW is connected at the thru port to play the role of polarizer by
      utilizing its polarization-dependent loss. With the present principle, the
      designed PBS has a footprint as small as only ~1.9 MUm * 3.7 MUm, which is the
      shortest PBS reported until now, even when large waveguide dimensions (e.g., the
      waveguide widths w(1,2) = ~300 nm and the gap width w(gap) = ~200 nm) are chosen
      to simplify the fabrication process. The numerical simulations show that the
      designed PBS has a very broad band (~120 nm) with an extinction ratio >12 dB and
      a large fabrication tolerance to allow a waveguide width variation of +/- 30 nm.

PMID- 24104634
TI  - Fast convergent Fourier modal method for the analysis of periodic arrays of
      graphene ribbons.
AB  - Li's Fourier factorization rules [J. Opt. Soc. Am. A13, 1870 (1996)] should be
      applied to achieve a fast convergence rate in the analysis of diffraction
      gratings with the Fourier modal method. I show, however, that Li's inverse rule
      cannot be applied for periodic patterns of graphene when the conventional
      boundary condition is used. I derive an approximate boundary condition in which a
      nonzero but sufficiently small height is assumed for the boundary. The proposed
      boundary condition enables us to apply the inverse rule, leading to a
      significantly improved convergence rate. A periodic array of graphene ribbons is
      in fact a special type of finite-conductivity strip grating, and thus the
      proposed approach is also applicable to these kinds of structures. 

PMID- 24104635
TI  - 3 W, 300 MUJ, 25 ns pulsed 473 nm blue laser based on actively Q-switched Nd:YAG
      single-crystal fiber oscillator at 946 nm.
AB  - We report the realization of a frequency doubled, actively Q-switched and
      polarized oscillator based on Nd:YAG single-crystal fiber. A laser output of 8 W,
      10 kHz, and 30 ns at 946 nm is reported. The laser is extracavity frequency
      doubled in a BiBO crystal to obtain 3 W and 300 MUJ of blue laser with a beam
      quality of M(2)y=1.12 and M(2)x=1.38. The obtained blue power is stable with a
      root-mean-square stability of less than 2% in 1 h. This is more than two times
      the previously reported average power and energy at 473 nm.

PMID- 24104636
TI  - Continuous wide-field characterization of drug release from skin substitute using
      off-axis interferometry.
AB  - We achieved continuous, noncontact wide-field imaging and characterization of
      drug release from a polymeric device in vitro by uniquely using off-axis
      interferometric imaging. Unlike the current gold-standard methods in this field,
      which are usually based on chromatography and spectroscopy, our method requires
      no user intervention during the experiment and involves less lab consumable
      instruments. Using a simplified interferometric imaging system, we experimentally
      demonstrate the characterization of anesthetic drug release (Bupivacaine) from a
      soy-based protein matrix, which is used as a skin substitute for wound dressing.
      Our results demonstrate the potential of interferometric imaging as an
      inexpensive and easy-to-use alternative for characterization of drug release in
      vitro. 

PMID- 24104637
TI  - High-energy, high-repetition-rate picosecond pulses from a quasi-CW diode-pumped
      Nd:YAG system.
AB  - We report on a high-power quasi-CW pumped Nd:YAG laser system, producing 130 mJ,
      64 ps pulses at 1064 nm wavelength with a repetition rate of 300 Hz. Pulses from
      a Nd:YVO(4) oscillator are first amplified by a regenerative amplifier to the
      millijoule level and then further amplified in quasi-CW diode-pumped Nd:YAG
      modules. Pulsed diode pumping enables a high gain at repetition rates of several
      hundred hertz, while keeping thermal effects manageable. Birefringence
      compensation and multiple thermal-lensing-compensated relay-imaging stages are
      used to maintain a top-hat beam profile. After frequency doubling, 75 mJ pulses
      are obtained at 532 nm. The intensity stability is better than 1.1%, which makes
      this laser an attractive pump source for a high-repetition-rate optical
      parametric amplification system.

PMID- 24104639
TI  - Dispersion mapping at the micrometer scale using tri-band optical frequency
      domain imaging.
AB  - Techniques to differentiate between materials are a powerful addition to the
      structural information traditionally available from optical coherence tomography
      images. We present label-free detection of water and lipid at a micrometer scale
      by evaluating their unique dispersion properties. Using a tri-band swept source
      configuration, we measure both beta(2) and beta(3) and show how to identify the
      two materials at sample thicknesses of 40 and 90 MUm, respectively.

PMID- 24104638
TI  - Modeling absorbance-modulation optical lithography in photochromic films.
AB  - A kinetic model describing the conversion of a photochromic layer under complex
      illumination conditions is applied to absorbance-modulation optical lithography
      to determine the influence of the material characteristics on the confinement to
      subdiffraction dimensions of the transmitted dose. We show that the most
      important parameters are the intensity ratio between the confining and writing
      beams, the overall absorption at the writing wavelength, the relative absorption
      coefficients, and the photoreaction quantum yields at the two wavelengths. As the
      confining beam ultimately determines the transferred dose pattern, we conclude
      that the modulation of the writing beam is not strictly necessary to produce
      subwavelength apertures. 

PMID- 24104640
TI  - Independence of elemental intensity ratio on plasma property during laser-induced
      breakdown spectroscopy.
AB  - The authors report that the elemental composition ratio of Ga to In in a CuIn(1
      x)Ga(x)Se(2) compound semiconductor, a thin-film solar cell material, can be
      measured with little influence of plasma property changes by laser-induced
      breakdown spectroscopy (lambda = 1064 nm, tau = 5 ns). It is shown that the
      similarity in excitation energy levels of the selected Ga and In emission lines
      and the fact that these elements belong to the same group of the periodic table
      are the critical factors ensuring the independence of intensity ratio on plasma
      conditions.

PMID- 24104641
TI  - Optical fiber in-line Mach-Zehnder interferometer based on dual internal mirrors
      formed by a hollow sphere pair.
AB  - We demonstrate a fiber in-line Mach-Zehnder interferometer based on dual internal
      mirrors formed by a hollow sphere pair and fabricated by femtosecond laser
      micromachining together with the fusion splicing technique. The hollow sphere
      surface adjacent to the fiber core can reflect part of the incident light beam to
      the air-cladding interface, where the light beam is reflected again before
      returning to the fiber core by another hollow sphere surface and recombining with
      the light beam remaining in the fiber core. Such an interferometer is miniature
      and robust, and is sensitive to environmental variations and allows simultaneous
      surrounding refractive index, temperature, and curvature measurement. 

PMID- 24104642
TI  - Dysprosium-doped PbGa2S4 laser generating at 4.3 MUm directly pumped by 1.7 MUm
      laser diode.
AB  - In this Letter, we demonstrate the pulsed and CW operation of the Dy:PbGa(2)S(4)
      laser directly pumped by the 1.7 MUm laser diode. In the pulsed regime (pulse
      duration 5 ms; repetition rate 20 Hz), the maximum mean output power of 9.5 mW
      was obtained with the slope efficiency of 9.3% with respect to the absorbed pump
      power. The generated wavelength was 4.32 MUm, and the laser beam cross section
      was approximately Gaussian on both axes. Stable CW laser generation was also
      successfully obtained with the maximum output power of 67 mW and the slope
      efficiency of 8%. Depopulation of the lower laser level by 1.7 MUm pump radiation
      absorption followed by 1.3 MUm upconversion fluorescence was demonstrated. These
      results show the possibility of construction of the compact diode-pumped solid
      state pulsed or CW laser generating at 4.3 MUm in the power level of tens mW
      operating at room temperature.

PMID- 24104643
TI  - Fabrication of large curvature microlens array using confined laser swelling
      method.
AB  - This Letter proposes a confined laser swelling method to fabricate large
      curvature microlens arrays. Unlike the polymers in conventional free laser
      swelling, the swelling polymer, which is methyl red-doped polymethyl methacrylate
      here, is confined between walls formed by a substrate and a flexible cover layer.
      Because swelling occurs in an enclosed space, decomposed segments remain in the
      matrix, resulting in a large hump at the side of the flexible cover layer. The
      results show that these humps are tens of times higher than those acquired by
      conventional methods and this method has potential for high efficiency large
      curvature microlens fabrication. 

PMID- 24104644
TI  - Evaluating Laguerre-Gaussian beams with an invariant parameter.
AB  - We define a new parameter for Laguerre-Gaussian (LG) beams, named Q(p,l), which
      is only related to mode indices p and l. This parameter is able to distinguish
      and evaluate LG beams. The Q(p,l) values are first calculated theoretically and
      then measured experimentally for several different LG beams. Another mode quality
      parameter, M(2) values, are also measured. The comparison between Q(p,l) and M(2)
      shows the same trend for the quality of the LG mode, while the measurement of
      Q(p,l) is much easier than M(2).

PMID- 24104645
TI  - Widely tunable dual-mode distributed feedback laser fabricated by selective area
      growth technology integrated with Ti heaters.
AB  - A widely tunable dual-mode distributed feedback (DFB) laser fabricated by
      selective area growth (SAG) technology integrated with Ti heaters was
      demonstrated. In the device, an original mode spacing of 4 nm was obtained by the
      simple SAG technology. Ti thin-film heaters were integrated with a novel
      procedure, which simplifies the fabrication of such heaters greatly. A large
      electrical resistance of the heaters is obtained at the same time, resulting in a
      high wavelength tuning efficiency. An accurate mode spacing as small as 0.34 nm
      and as large as 8.06 nm is achieved, which corresponds to a wide beat frequency
      range from 42.2 GHz to 1 THz. The simple fabrication process indicates that it is
      promising for reducing the cost of dual-mode DFB laser in fabricating self
      pulsation lasers and THz generators.

PMID- 24104646
TI  - Restoration of blurred images due to phase distortion based on polarization
      insensitive phase conjugation in second-order nonlinear medium.
AB  - Broadband and polarization-insensitive phase conjugation, achieved based on
      difference-frequency generation in a second-order nonlinear composite consisting
      of stacked KTiOPO(4) (KTP) plates, was exploited to restore blurred images due to
      phase distortion as a novel scheme. Due to the quasi-phase matching in the
      stacked KTP crystals, our result reveals that the image restoration is
      insensitive to the polarization direction and wavelength of the input beam.

PMID- 24104647
TI  - Fundamental limit to the use of effective medium theories in optics.
AB  - The effective medium refractive index of a surface-bound submonolayer of
      polystyrene nanospheres in water is found to be ill-defined below a rather
      specific sphere occupied area limit. The submonolayer takes on a recognizable
      thickness and refractive index only when the average center separation between
      spheres is at or below the inverse of the wavenumber. An anticipated limit to the
      Maxwell Garnett theory is therefore confirmed. It is proposed that this reveals a
      fundamental property of light scattering that is not of the Huygens spherical
      secondary wave type. 

PMID- 24104649
TI  - 20 W continuous-wave cladding-pumped Nd-doped fiber laser at 910 nm.
AB  - We demonstrate a double-clad fiber laser operating at 910 nm with a record power
      of 20 W. Laser emission on the three-level scheme is enabled by the combination
      of a small inner cladding-to-core diameter ratio and a high brightness pump
      source at 808 nm. A laser conversion efficiency as high as 44% was achieved in CW
      operating regime by using resonant fiber Bragg reflectors at 910 nm that prevent
      the lasing at the 1060 nm competing wavelength. Furthermore, in a master
      oscillator power-amplifier scheme, an amplified power of 14.8 W was achieved at
      914 nm in the same fiber.

PMID- 24104648
TI  - Identification of a dynamical model of a thermally actuated deformable mirror.
AB  - Using the subspace identification technique, we identify a finite dimensional,
      dynamical model of a recently developed prototype of a thermally actuated
      deformable mirror (TADM). The main advantage of the identified model over the
      models described by partial differential equations is its low complexity and low
      dimensionality. Consequently, the identified model can be easily used for high
      performance feedback or feed-forward control. The experimental results show good
      agreement between the dynamical response predicted by the model and the measured
      response of the TADM. 

PMID- 24104650
TI  - Coupler-apodized Bragg-grating add-drop filter.
AB  - We demonstrate an apodization technique using tapered coupler gaps in grating
      assisted asymmetric couplers, which circumvents the need for tapered waveguide
      perturbations and enables a higher tolerance to fabrication errors. A high
      sidelobe suppression ratio of 30 dB has been obtained on the submicrometer
      silicon-on-insulator platform using a CMOS-compatible photonics process with 193
      nm lithography.

PMID- 24104651
TI  - 2.7 MUm emission in Er3+:CaF2 nanocrystals embedded oxyfluoride glass ceramics.
AB  - Using conventional melt-quenching and subsequent thermal treatment, Er(3+) doped
      CaF(2) transparent glass ceramic (GC) was prepared. X-ray diffraction and high
      resolution transmission electron microscopy confirmed the formation and
      microstructure of CaF(2) nanocrystals in glass. An energy-dispersive spectrometer
      was used to investigate the distribution of Er(3+) ions and CaF(2) nanocrystals
      in glass. It was found that Er(3+) ions prefer to concentrate in the CaF(2)
      nanocrystals rather than in a glass matrix, and the amount of Er(3+) ions plays a
      key role in the formation of CaF(2) nanocrystals in a glass matrix with the
      Er(3+) ions as nucleating agent. An intense 2.7 MUm emission due to Er(3+):
      I(11/2)4 -> I(13/2)4 was achieved upon excitation at 980 nm with a laser diode,
      while the 2.7 MUm emission can be neglected in the as-prepared glass counterpart,
      which confirmed the incorporation of Er(3+) ions into CaF(2) nanocrystals. An
      obvious enhancement of 2.7 MUm emerged in the GC doped with 3% Er(3+) and heat
      treated at 620  degrees C.

PMID- 24104652
TI  - High efficiency Nd:YAG ceramic eye-safe laser operating at 1442.8 nm.
AB  - We report on a diode-pumped Nd:YAG ceramic laser operating at 1442.8 nm for the
      first time. In our experiment, two different Nd:YAG ceramics with the Nd-doped
      concentrations of 1.0 and 0.6 at. % and a Nd:YAG with the Nd-doped concentration
      of 1.0 at. % were used as the laser gain mediums, respectively. At a pump power
      of 20.7 W, a maximum output power of up to 3.96 W with optical-to-optical
      efficiency of up to 19.1% was obtained by using the 1.0 at. % Nd-doped ceramic as
      the laser gain medium. To the best of our knowledge, this is the highest output
      power of a LD-pumped 1.44 MUm Nd:YAG ceramic laser and the highest optical-to
      optical efficiency of a LD-pumped 1.44 MUm Nd-doped crystal laser.

PMID- 24104653
TI  - Plasmonic waveguides with low polarization dependence.
AB  - Plasmonic waveguides essentially support only transverse magnetic modes. A novel
      plasmonic waveguide consisting of hybrid plasmonic waveguides in both vertical
      and horizontal directions is proposed to reduce the polarization dependence. In a
      combined waveguide, surface plasmon polariton (SPP) modes polarized in both
      vertical and horizontal directions exist in the correspondingly oriented hybrid
      plasmonic waveguide. In an optimized structure, anticrossing mode coupling is
      observed between these two SPP modes with a low birefringence by finite
      difference time-domain simulation. The energy flux clearly shows the polarization
      selective coupling between the polarized guided modes in the feeding silicon
      waveguide and those in the combined waveguide. Coupling efficiency above 65% is
      obtained for both polarizations. The proposed plasmonic combined waveguide has a
      potential application in guiding and processing of light from a fiber with a
      random polarization state. 

PMID- 24104654
TI  - Strip/slot hybrid arsenic tri-sulfide waveguide with ultra-flat and low
      dispersion profile over an ultra-wide bandwidth.
AB  - A strip/slot hybrid arsenic tri-sulfide waveguide with a horizontal silicon
      dioxide slot is proposed. The waveguide exhibits an ultra-flat and low dispersion
      profile with four zero-dispersion wavelengths. Tuning structural parameters of
      the waveguide causes tailoring the dispersion. There is only a low dispersion of
      approximately +/- 3 ps/(nm . km) over a 1035 nm bandwidth. It is shown that the
      waveguide has less sensitivity to the variations of the structural parameters and
      fabrication errors compared to silicon waveguides. Moreover, nonlinear
      coefficient, figure of merit, third-order dispersion and phase-matching condition
      in four-wave mixing are studied. This waveguide has a great potential for
      nonlinear applications in a wide range of wavelengths.

PMID- 24104655
TI  - Polarization-independent coherent perfect absorption by a dipole-like
      metasurface.
AB  - We show that polarization-independent coherent perfect absorption can be realized
      in a simple dipole-like metasurface by precisely engineering the ratio between
      the scattering loss gamma(s) and the dissipation loss gamma(l). This effect can
      be traced to a critical condition on the scattering matrix in a dipolar picture,
      which requires that the scattering and dissipation losses are equivalent, i.e.,
      gamma(s) = gamma(l), at the resonant frequency f(0). This work expands the
      capability of metasurface in getting extreme optical properties, allowing for
      many potential applications.

PMID- 24104656
TI  - Low-loss terahertz waveguide Bragg grating using a two-wire waveguide and a paper
      grating.
AB  - We propose a low-loss terahertz waveguide Bragg grating (TWBG) fabricated using a
      plasmonic two-wire waveguide and a micromachined paper grating for potential
      applications in terahertz (THz) communications. Two TWBGs were fabricated with
      different periods and lengths. Transmission spectra of these TWBGs show 16 dB
      loss and 14 dB loss in the middle of their respective stop bands at 0.637 and
      0.369 THz, with Q factors of 142 and 105, respectively. Insertion loss of 1-4 dB
      in the whole 0.1-0.7 THz region was also measured. Finally, TWBG modal dispersion
      relations, modal loss, and field distributions were studied numerically, and low
      loss, high-coupling-efficiency operation of TWBGs was confirmed.

PMID- 24104657
TI  - Observation of photorefractive surface waves in self-defocusing LiNbO3:Fe
      crystal.
AB  - Photorefractive (PR) surface waves (SWs) in self-defocusing LiNbO(3):Fe are
      studied theoretically and experimentally. We demonstrate that SWs can also be
      formed in a self-defocusing nonlinear medium and that the nonlocal nonlinearity
      (such as the diffusion component of PR nonlinearity in this Letter) is the
      essential cause. The forming process of PR SWs with a self-deflection course of
      light beams has been observed. The results indicate the possibility of
      concentrating light energy in self-defocusing media, taking advantage of SWs.

PMID- 24104658
TI  - All-fiber optical filter with an ultranarrow and rectangular spectral response.
AB  - Optical filters with an ultranarrow and rectangular spectral response are highly
      desired for high-resolution optical/electrical signal processing. An all-fiber
      optical filter based on a fiber Bragg grating with a large number of phase shifts
      is designed and fabricated. The measured spectral response shows a 3 dB bandwidth
      of 650 MHz and a rectangular shape factor of 0.513 at the 25 dB bandwidth. This
      is the narrowest rectangular bandpass response ever reported for an all-fiber
      filter, to the best of our knowledge. The filter has also the intrinsic
      advantages of an all-fiber implementation.

PMID- 24104659
TI  - Revealing interference by continuous variable discordant states.
AB  - In general, a pair of uncorrelated Gaussian states mixed in a beam splitter (BS)
      produces a correlated state at the output. However, when the inputs are identical
      Gaussian states the output state is equal to the input, and no correlations
      appear, as the interference had not taken place. On the other hand, since
      physical phenomena do have observable effects, and the BS is there, a question
      arises on how to reveal the interference between the two beams. We prove
      theoretically and demonstrate experimentally that this is possible if at least
      one of the two beams is prepared in a discordant, i.e., Gaussian correlated,
      state with a third beam. We also apply the same technique to reveal the erasure
      of polarization information. Our experiment involves thermal states and the
      results show that Gaussian discordant states, even when they show a positive
      Glauber P-function, may be useful to achieve specific tasks. 

PMID- 24104660
TI  - Miniature varifocal objective lens for endomicroscopy.
AB  - A miniature catadioptric lens for endoscopic imaging based on the principle of
      wavelength division multiplexing is presented. We demonstrate change of the
      magnification and the field of view (FOV) of the lens without any mechanical
      adjustment of the optical elements. The lens provides magnifications of ~-1.5* at
      406-750 nm and ~-0.2* at 800 nm. The lens is used to demonstrate large-FOV (1.3
      mm) reflectance imaging and high-resolution (0.57 MUm) multiphoton fluorescence
      imaging of unstained mouse tissues.

PMID- 24104661
TI  - Precision Doppler measurements with steep dispersion.
AB  - Controlling the group velocity of light is a valuable resource for quantum and
      classical optical processing and high performance sensor technologies. In this
      context, slow-light (SL) and the associated steep dispersion have been proposed
      to increase the sensitivity of certain types of interferometers. Here, we show
      that the interaction of two intensity-balanced light beams in a SL medium can be
      used to detect Doppler shifts with extremely high sensitivity. By using this
      effect in a liquid crystal light-valve, we have been able to measure Doppler
      shifts as low as 1 MUHz with an integration time of only 1 s. The shot noise
      limited sensitivity inversely depends on the steepness of the beam-coupling
      dispersive response. This method allows for remote sensing of very slowly moving
      objects with a linear response over 5 orders of magnitude.

PMID- 24104662
TI  - Imaging using cylindrical vector beams in a high-numerical-aperture microscopy
      system.
AB  - Imaging of object structures using cylindrical vector beams in an aplanatic solid
      immersion lens (SIL) microscope is investigated. Based on a complete optical
      model of an aplanatic SIL microscope, images of some object structures using
      radial polarization, azimuthal polarization, and azimuthal vortex beams are
      simulated. Some interesting imaging effects of these object structures are
      observed. For example, counterintuitively, it is found that, compared to linear
      and circular polarizations, radial polarization requires a larger pinhole to
      acquire a good image and resolution. Similarly, it is shown that an azimuthal
      vortex beam provides good images for a variety of object structures and pinhole
      sizes. Theories and explanations are provided to justify the observed effects.
      The presented results play an important role in high-numerical-aperture optical
      imaging. 

PMID- 24104663
TI  - GeO2-SiO2-chitosan-medium-coated hollow optical fiber for cell immobilization.
AB  - A GeO(2)-SiO(2)-chitosan-medium (GSCM)-coated hollow optical fiber (HOF) is
      proposed. The HOF consists of three parts: the fiber core (air), cladding
      (SiO(2)), and coating (GSCM), which shows the highest refractive index of the
      three. The HOF's luminescence properties and surface morphology are investigated.
      Their adsorption capacity for Rhodopseudomonas palustris CQK 01 is also assayed.
      We discovered that when the amount of 2GeO(2)-SiO(2) sol dopant is 0.9 mass
      percent, the HOF exhibits the highest luminous intensity and uniform light
      distribution, and the adsorption capacity for the cell is 3.2 times higher than
      that of a normal solid optical fiber.

PMID- 24104664
TI  - Absorption efficiency enhancement in inorganic and organic thin film solar cells
      via plasmonic honeycomb nanoantenna arrays.
AB  - We demonstrate theoretically that by embedding plasmonic honeycomb nanoantenna
      arrays into the active layers of inorganic (c-Si) and organic
      (P3HT:PCBM/PEDOT:PSS) thin film solar cells, absorption efficiency can be
      improved. To obtain the solar cell absorption spectrum that conforms to the solar
      radiation, spectral broadening is achieved by breaking the symmetry within the
      Wigner-Seitz unit cell on a uniform hexagonal grid. For optimized honeycomb
      designs, absorption efficiency enhancements of 106.2% and 20.8% are achieved for
      c-Si and P3HT:PCBM/PEDOT:PSS thin film solar cells, respectively. We have
      demonstrated that the transverse modes are responsible for the enhancement in c
      Si solar cells, whereas both the longitudinal and transverse modes, albeit
      weaker, are the main enhancement mechanisms for P3HT:PCBM/PEDOT:PSS solar cells.
      For both inorganic and organic solar cells, the absorption enhancement is
      independent of polarization. 

PMID- 24104665
TI  - Control of terahertz emission in photoconductive antennas through an additional
      optical continuous wave.
AB  - The manipulation of the operating conditions of photoconductive antennas by means
      of an additional continuous wave (CW) is reported. It is used to control a fiber
      based terahertz (THz) time-domain-spectroscopy system at telecom wavelengths. The
      injection of an optical CW into the transmitter allows the control of the THz
      amplitude without causing major degradation to the system performance. This, for
      instance, can be exploited to perform modulation of the THz signal. 

PMID- 24104666
TI  - Three-dimensional movable metamaterial using electric split-ring resonators.
AB  - We have demonstrated a three-dimensional movable metamaterial (MM) with
      reconfigurable electric split-ring resonators (eSRR) at terahertz frequencies.
      This is accomplished by making planar arrays of eSRR with movable stress curved
      beams (eSRR-MSCBs) which are actuated out-of-plane by electrostatic force. Our
      results have demonstrated that the eSRR-MSCBs possess blueshifting capabilities
      and polarization dependent state at terahertz frequencies, while such adaptive
      MMs offer significant potential in realizing electromagnetic functionality with
      diversified applications, such as sensors, switches, and filters. 

PMID- 24104667
TI  - Photonic crystal nanofishbone nanocavity.
AB  - We propose a photonic crystal (PhC) nanofishbone (NFB) nanocavity, which confines
      an ultrahigh Q (~1.8 * 10(7)) transverse-magnetic (TM) mode. With thin slab
      thickness and only few PhC periods, the TM mode in NFB nanocavity shows higher Q,
      larger confinement factor and smaller mode volume than that in PhC nanobeam
      nanocavity, while the total etched-surface area is also significantly reduced.
      This PhC NFB nanocavity with very compact device size will be very beneficial for
      quantum cascade lasers, plasmonic nanolasers, and other applications needing high
      Q TM modes.

PMID- 24104668
TI  - Isotropic spiral plasmonic metamaterial for sensing large refractive index
      change.
AB  - We numerically investigate the optical properties of a spiral G-shaped
      metamaterial, which exhibits both a sharp resonance with a high-quality factor
      and a broad resonance with a long linear slope in the near-infrared region. By
      employing the sharp resonating mode, refractive index sensing with sensitivity up
      to 410 nm/RIU is demonstrated theoretically. In addition, the metamaterial shows
      single wavelength sensing ability, which allows fast determination of
      environmental refractive index changes as large as 0.5 by simply monitoring
      variations in the transmitted intensity of a certain wavelength, which will be
      beneficial to the development of refractive index sensors based on monochromatic
      light sources and detectors. As the resonances are independent of the
      polarization direction of a linearly polarized wave, the sensor manufacturing
      process will benefit as a result of the lack of an alignment requirement for the
      axis of polarizers with the metamaterials' orientation.

PMID- 24104669
TI  - Generation of a flat optical frequency comb based on a cascaded polarization
      modulator and phase modulator.
AB  - A scheme to generate a flat optical frequency comb (OFC) with a fixed phase
      relationship between the comb lines is proposed and experimentally demonstrated
      based on a cascaded polarization modulator (PolM) and phase modulator. Because
      the PolM introduces more controllable parameters compared with the conventional
      intensity modulator, 9, 11, and 13 comb lines can be generated with relatively
      low RF powers, or 15, 17, and 19 comb lines can be obtained if high RF powers are
      applied. The experimentally generated 9, 11, and 13 OFCs have a flatness of 1,
      1.3, and 2.1 dB, respectively. The scheme requires no DC bias to the modulators,
      no optical filter, and no frequency divider or multiplier, which is simple and
      stable.

PMID- 24104671
TI  - Polymer-stabilized liquid crystal microlens array with large dynamic range and
      fast response time.
AB  - We report a polymer-stabilized liquid crystal (LC) microlens array with a large
      dynamic range and fast response time. The top substrate has a planar indium-tin
      oxide (ITO) electrode, while the bottom substrate has two patterned ITO
      electrodes for generating a fringing field and uniform longitudinal field. The
      fringing field is utilized to create the desired gradient refractive index
      profile in the LC/monomer layer, which is later stabilized by UV curing to form
      polymer networks. To tune the focal length, we apply a longitudinal field to
      change the lens shape. This microlens array offers several attractive features,
      such as large dynamic range, fast response time, and good mechanical stability. 

PMID- 24104670
TI  - Enhancement of photoacoustic tomography by ultrasonic computed tomography based
      on optical excitation of elements of a full-ring transducer array.
AB  - Photoacoustic computed tomography (PACT) is a hybrid technique that combines
      optical excitation and ultrasonic detection to provide high-resolution images in
      deep tissues. In the image reconstruction, a constant speed of sound (SOS) is
      normally assumed. This assumption, however, is often not strictly satisfied in
      deep tissue imaging, due to acoustic heterogeneities within the object and
      between the object and the coupling medium. If these heterogeneities are not
      accounted for, they will cause distortions and artifacts in the reconstructed
      images. In this Letter, we incorporated ultrasonic computed tomography (USCT),
      which measures the SOS distribution within the object, into our full-ring array
      PACT system. Without the need for ultrasonic transmitting electronics, USCT was
      performed using the same laser beam as for PACT measurement. By scanning the
      laser beam on the array surface, we can sequentially fire different elements. As
      a first demonstration of the system, we studied the effect of acoustic
      heterogeneities on photoacoustic vascular imaging. We verified that constant SOS
      is a reasonable approximation when the SOS variation is small. When the variation
      is large, distortion will be observed in the periphery of the object, especially
      in the tangential direction. 

PMID- 24104672
TI  - Mid-infrared dual-comb spectroscopy with an optical parametric oscillator.
AB  - We present the first implementation of mid-infrared dual-comb spectroscopy with
      an optical parametric oscillator. Methane absorption spectroscopy was
      demonstrated with a resolution of 0.2 cm(-1) (5 GHz) at an acquisition time of
      ~10.4 ms over a spectral coverage at 2900-3050 cm(-1). The average power from
      each individual mid-infrared comb line was ~1 MUW, representing a power level
      much greater than typical difference-frequency-generation sources. Mid-infrared
      dual-comb spectroscopy opens up unique opportunities to perform broadband
      spectroscopic measurements with high resolution, high requisition rate, and high
      detection sensitivity.

PMID- 24104673
TI  - All-fiber polarization-dependent optical vortex beams generation via flexural
      acoustic wave.
AB  - We report on a novel type of optical mode conversion in fiber acousto-optics. The
      all-fiber narrowband complete transformation of the fundamental mode into the
      frequency downshifted optical vortex beam of topological charge +1 or -1 via a
      lowest-order flexural acoustic wave is theoretically demonstrated. Moreover, such
      a process is found to be polarization dependent: both the topological charge and
      polarization state of the produced optical vortex are governed by the circular
      polarization handedness of the input mode. The possible applications of the
      established conversion for optical vortex manipulation are discussed. 

PMID- 24104674
TI  - High-power dense wavelength division multiplexing of multimode diode laser
      radiation based on volume Bragg gratings.
AB  - We present a dense wavelength division multiplexer based on volume Bragg gratings
      (VBGs) with a channel spacing of Deltalambda = 1.5 nm. Multiplexing efficiencies
      of etaSM = 97% have been demonstrated with single-mode, frequency-stabilized
      diode laser radiation. By use of VBGs in an external-cavity laser we constrict
      the spectral bandwidth of passively cooled multimode diode laser bars with 19
      broad-area emitters to deltalambda95% = 120 pm. When the multimode high-power
      diode laser radiation with a beam propagation factor of M(2) ~ 45 is overlaid,
      the multiplexing efficiency decreases to etaMM = 85%. Temperature control of the
      VBGs expands the high-efficiency operation range.

PMID- 24104675
TI  - Numerical study of the suppressed efficiency droop in blue InGaN LEDs with
      polarization-matched configuration.
AB  - In blue InGaN light-emitting diodes (LEDs), the intuitive approaches to suppress
      Auger recombination by reducing carrier density, e.g., increasing the number of
      quantum wells (QWs) and thickening the width of wells, suffer from nonuniform
      carrier distribution and more severe spatial separation of electron and hole wave
      functions. To resolve this issue, LED structures with thick InGaN wells and
      polarization-matched AlGaInN barriers are proposed theoretically. Furthermore,
      the number of QWs is reduced for the purpose of mitigating the additional
      compressive strain in AlGaInN barriers. Simulation results reveal that, in the
      proposed structures, the quantum-confined Stark effect in strained wells is
      nearly eliminated through the utilization of polarization-matched barriers, which
      efficiently promotes internal quantum efficiency. Furthermore, the phenomenon of
      efficiency droop is also markedly improved because of the uniformly distributed
      or dispersed carriers, and accordingly the suppressed Auger recombination. 

PMID- 24104676
TI  - Three-dimensional imaging and visualization using off-axially distributed image
      sensing.
AB  - This Letter presents an off-axially distributed image sensing (ODIS) system for
      three-dimensional (3D) imaging and visualization. The off-axially distributed
      sensing method provides both lateral and longitudinal perspectives for 3D scenes
      even though the sensor moves along a slanted, one-dimensional path. A 3D volume
      is generated from a set of recorded images by use of a computational algorithm
      based on ray backprojection. Preliminary experimental results are presented to
      illustrate the feasibility of the proposed system. To the best of our knowledge,
      this is the first report on 3D imaging and visualization using ODIS. 

PMID- 24104677
TI  - Low polarization-sensitive asymmetric multi-quantum well semiconductor amplifier
      for next-generation optical access networks.
AB  - A broadband and low-polarization-sensitive multi-quantum well semiconductor
      optical amplifier with an asymmetric structure is reported for operation in the E
      band wavelength range. A gain peak of 20 dB for a bandwidth of more than 50 nm is
      measured for both TE and TM polarizations. A maximum polarization sensitivity of
      3 dB is measured for a broad wavelength range from 1340 to 1440 nm.

PMID- 24104678
TI  - Birefringence dispersion compensation demodulation algorithm for polarized low
      coherence interferometry.
AB  - A demodulation algorithm based on the birefringence dispersion characteristics
      for a polarized low-coherence interferometer is proposed. With the birefringence
      dispersion parameter taken into account, the mathematical model of the polarized
      low-coherence interference fringes is established and used to extract phase shift
      information between the measured coherence envelope center and the zero-order
      fringe, which eliminates the interferometric 2 pi ambiguity of locating the zero
      order fringe. A pressure measurement experiment using an optical fiber Fabry
      Perot pressure sensor was carried out to verify the effectiveness of the proposed
      algorithm. The experiment result showed that the demodulation precision was 0.077
      kPa in the range of 210 kPa, which was improved by 23 times compared to the
      traditional envelope detection method.

PMID- 24104679
TI  - Holographic display based on a spatial DMD array.
AB  - The image space of the reconstructed image from the hologram displayed on a
      digital micromirror device (DMD) is defined by the diffraction pattern induced by
      the 2D pixel pattern of the DMD, which works as a 2D blazed grating. Within this
      space, a reconstructed image of 100 mm * 20 mm is spatially multiplexed by a 2 *
      5 DMD array that is aligned on a board, without using any extra optics. Each DMD
      chip reconstructs an image piece of the size 20 mm (width) * 10 mm (height). The
      reconstructed image looks somewhat noisy but regenerates the original object
      image faithfully.

PMID- 24104680
TI  - High light-directing micrometer-sized parabolic mirror arrays.
AB  - Excellent light-directing abilities are demonstrated by well-designed three
      dimensional micrometer-sized parabolic mirrors that are fabricated by direct
      laser writing and subsequent surface coating of titanium and silver. The full
      width at half-maximum of the measured light divergence for the mirrors with
      different geometries is much less than 20 MUm, even when the height is up to 130
      MUm. These results are beneficial for developing highly collimating light
      emitting diodes. The simulation for the mirrors reveals that the electric field
      intensity distribution is highly confined toward the central axis of the mirrors,
      which is consistent with the experimental results.

PMID- 24104681
TI  - Magnetic fluid-filled microhole in the collapsed region of a photonic crystal
      fiber for the measurement of a magnetic field.
AB  - A method for measurement of a magnetic field by filling a microhole with magnetic
      fluid (MF) in a photonic crystal fiber (PCF) is presented and experimentally
      demonstrated. A microhole is created in the collapsed region between the PCF and
      the single-mode fiber by using femtosecond laser micromachining, and a PCF-based
      Mach-Zehnder interferometer is formed. The MF is filled into the microhole. Due
      to the tunable refractive index property of the MF, the mode field diameter of
      the propagation light is changed with the external magnetic field, and the
      magnetic field can be detected by measuring the visibility contrast of the white
      light interferogram. The experimental results show that sensitivity of up to
      0.042 dB/Oe is achieved.

PMID- 24104683
TI  - Absolute frequency of cesium 6S-8S 822 nm two-photon transition by a high
      resolution scheme.
AB  - We present an alternative scheme for determining the frequencies of cesium (Cs)
      atom 6S-8S Doppler-free transitions. With the use of a single electro-optical
      crystal, we simultaneously narrow the laser linewidth, lock the laser frequency,
      and resolve a narrow spectrum point by point. The error budget for this scheme is
      presented, and we prove that the transition frequency obtained from the Cs cell
      at room temperature and with one-layer MU-metal shielding is already very near
      that for the condition of zero collision and zero magnetic field. We point out
      that a sophisticated linewidth measurement could be a good guidance for choosing
      a suitable Cs cell for better frequency accuracy. 

PMID- 24104684
TI  - Compact all-fiber laser delivering conventional and dissipative solitons.
AB  - We report the simultaneous generation of conventional soliton (CS) and
      dissipative soliton (DS) in a mode-locked fiber laser exploiting chirped fiber
      Bragg grating and four-port circulator. The bandwidth and duration of the CS are
      0.28 nm and 15.1 ps, respectively. However, the giant-chirp DS exhibits a quasi
      rectangular spectrum with a bandwidth of 9.5 nm. The duration of the output DS is
      7.3 ps and can be compressed to 0.55 ps external to the cavity. Our numerical
      results agree well with the experimental observations. The flexible all-fiber
      laser can provide three different pulse sources, which is convenient and
      attractive for practical applications.

PMID- 24104685
TI  - Mid-infrared laser filamentation in molecular gases.
AB  - We observed the filamentation of mid-infrared ultrashort laser pulses (3.9 MUm,
      80 fs) in molecular gases. It efficiently generates a broadband supercontinuum
      over two octaves in the 2.5-6 MUm spectral range, with a red-shift up to 500 nm
      due to the Raman effect, which dominates over the blue shift induced by self
      steepening and the gas ionization. As a result, the conversion efficiency into
      the Stokes region (4.3-6 MUm) 65% is demonstrated.

PMID- 24104686
TI  - Cloning and characterization of a biotic-stress-inducible glutathione transferase
      from Phaseolus vulgaris.
AB  - Glutathione transferases (GSTs, EC 2.5.1.18) are ubiquitous proteins in plants
      that play important roles in stress tolerance and in the detoxification of toxic
      chemicals and metabolites. In this study, we systematically examined the
      catalytic diversification of a GST isoenzyme from Phaseolus vulgaris (PvGST)
      which is induced under biotic stress treatment (Uromyces appendiculatus
      infection). The full-length cDNA of this GST isoenzyme (termed PvGSTU3-3) with
      complete open reading frame, was isolated using RACE-RT and showed that the
      deduced amino acid sequence shares high homology with the tau class plant GSTs.
      PvGSTU3-3 catalyzes several different reactions and exhibits wide substrate
      specificity. Of particular importance is the finding that the enzyme shows high
      antioxidant catalytic function and acts as hydroperoxidase, thioltransferase, and
      dehydroascorbate reductase. In addition, its K m for GSH is about five to ten
      times lower compared to other plant GSTs, suggesting that PvGSTU3-3 is able to
      perform efficient catalysis under conditions where the concentration of reduced
      glutathione is low (e.g., oxidative stress). Its ability to conjugate GSH with
      isothiocyanates may provide an additional role for this enzyme to act as a
      regulator of the released isothiocyanates from glucosinolates as a response of
      biotic stress. Molecular modeling showed that PvGSTU3-3 shares the same overall
      fold and structural organization with other plant cytosolic GSTs, with major
      differences at their hydrophobic binding sites (H-sites) and some differences at
      the level of C-terminal domain and the linker between the C- and N-terminal
      domains. PvGSTU3-3, in general, exhibits restricted ability to bind xenobiotics
      in a nonsubstrate manner, suggesting that the biological role of PvGSTU3-3, is
      restricted mainly to the catalytic function. Our findings highlight the
      functional and catalytic diversity of plant GSTs and demonstrate their pivotal
      role for addressing biotic stresses in Phaseolus vulgaris. 

PMID- 24104687
TI  - RNA-seq analysis of antibiotic-producing Bacillus subtilis SC-8 in response to
      signal peptide PapR of Bacillus cereus.
AB  - Bacillus subtilis SC-8 produces an antibiotic that has narrow antagonistic
      activity against bacteria in the Bacillus cereus group. In B. cereus group
      bacteria, peptide-activating PlcR (PapR) plays a significant role in regulating
      the transcription of virulence factors. When B. subtilis SC-8 and B. cereus are
      co-cultured, PapR is assumed to stimulate antibiotic production by B. subtilis SC
      8. To better understand the effect of PapR on this interspecies interaction, the
      global transcriptome profile of B. subtilis SC-8 was analyzed in the presence of
      PapR. Significant changes were detected in 12.8 % of the total transcripts. Genes
      related to amino acid transport and metabolism (16.5 %) and transcription (15 %)
      were mainly upregulated, whereas genes involved in carbohydrate transport and
      metabolism (12.7 %) were markedly downregulated. The expression of genes related
      to transcription, including several transcriptional regulators and proteins
      involved in tRNA biosynthesis, was increased. The expression levels of genes
      associated with several transport systems, such as antibiotic, cobalt, and iron
      complex transporters, was also significantly altered. Among the downregulated
      genes were transcripts associated with spore formation, the subtilosin A gene
      cluster, and nitrogen metabolism. 

PMID- 24104688
TI  - Optimization of dilute sulfuric acid pretreatment to maximize combined sugar
      yield from sugarcane bagasse for ethanol production.
AB  - Increasing fermentable sugar yields per gram of biomass depends strongly on
      optimal selection of varieties and optimization of pretreatment conditions. In
      this study, dilute acid pretreatment of bagasse from six varieties of sugarcane
      was investigated in connection with enzymatic hydrolysis for maximum combined
      sugar yield (CSY). The CSY from the varieties were also compared with the results
      from industrial bagasse. The results revealed considerable differences in CSY
      between the varieties. Up to 22.7 % differences in CSY at the optimal conditions
      was observed. The combined sugar yield difference between the best performing
      variety and the industrial bagasse was 34.1 %. High ratio of carbohydrates to
      lignin and low ash content favored the release of sugar from the substrates. At
      mild pretreatment conditions, the differences in bioconversion efficiency between
      varieties were greater than at severe condition. This observation suggests that
      under less severe conditions the glucose recovery was largely determined by
      chemical composition of biomass. The results from this study support the
      possibility of increasing sugar yields or improving the conversion efficiency
      when pretreatment optimization is performed on varieties with improved
      properties. 

PMID- 24104689
TI  - Biodegradation of tetracycline under various conditions and effects on microbial
      community.
AB  - Five hundred tons of antibiotics are consumed yearly in the world. In this study,
      the biodegradation characteristics of tetracycline (TET) under nitrate-reducing,
      sulfate-reducing, and methanogenic conditions were determined by batch tests.
      Also, effects of TET on mixed microbial cultures were revealed by microbiological
      analysis. In this scope, gas generation and composition, dissolved organic
      carbon, and electron acceptor concentrations were monitored during 120 days.
      Additionally, changes on quantities of specific microbial groups were determined
      by Q-PCR. TET showed non-biodegradable behavior under nitrate- and sulfate
      reducing conditions, whereas slightly biodegradable behavior under methanogenic
      conditions approximately 46 % degradation. The effects of TET on the abundance of
      mixed culture varied according to taxonomic units. Sulfate-reducing bacteria were
      inhibited by TET, while archaeal, bacterial, and methanogenic populations were
      not affected significantly. 

PMID- 24104690
TI  - Controlled production of exopolysaccharides from Enterobacter A47 as a function
      of carbon source with demonstration of their film and emulsifying abilities.
AB  - The bacterium Enterobacter A47 has demonstrated the ability to synthesise
      distinct exopolysaccharides (EPS) as a function of the substrate used. The
      culture's performance was evaluated in experiments using either glucose or
      xylose, as single carbon sources, and compared with the substrate (glycerol) used
      in previous studies. The highest EPS production (13.23 g L(-1)) was obtained in
      the glucose fed assay, with a volumetric productivity of 3.38 g L(-1) day(-1).
      The use of xylose resulted in lower productivity (1.39 g L(-1) day(-1)). The
      synthesised polymers have the same main sugar monomers (fucose, glucose,
      galactose and glucuronic acid), but their relative proportion varied with the
      substrate used. The acyl groups' content and composition were also affected by
      the substrate used. The polymers produced from glycerol (EPS-s) and glucose (EPS
      g) had identical shear-thinning behaviour and good emulsion-stabilising capacity
      and their films had similar mechanical and water vapour properties. However, the
      emulsions stabilised with EPS-g were less stable and destabilised within short
      periods of time or when subjected to heat and freezing/thawing procedures. On the
      other hand, the polymer produced from xylose had little emulsion-stabilising
      capacity and lower apparent viscosity than EPS-s and EPS-g, but its films were
      considerably more elastic. 

PMID- 24104691
TI  - The antimicrobial effects and metabolomic footprinting of carboxyl-capped bismuth
      nanoparticles against Helicobacter pylori.
AB  - Organic salts of bismuth are currently used as antimicrobial agents against
      Helicobacter pylori. This study evaluated the antibacterial effect of elemental
      bismuth nanoparticles (Bi NPs) using a serial agar dilution method for the first
      time against different clinical isolates and a standard strain of H. pylori. The
      Bi NPs were biologically prepared and purified by a recently described method and
      subjected to further characterization by infrared spectroscopy and anti-H. pylori
      evaluation. Infrared spectroscopy results showed the presence of carboxyl
      functional groups on the surface of biogenic Bi NPs. These biogenic nanoparticles
      showed good antibacterial activity against all tested H. pylori strains. The
      resulting MICs varied between 60 and 100 MUg/ml for clinical isolates of H.
      pylori and H. pylori (ATCC 26695). The antibacterial effect of bismuth ions was
      also tested against all test strains. The antimicrobial effect of Bi ions was
      lower than antimicrobial effect of bismuth in the form of elemental NPs. The
      effect of Bi NPs on metabolomic footprinting of H. pylori was further evaluated
      by (1)H NMR spectroscopy. Exposure of H. pylori to an inhibitory concentration of
      Bi NPs (100 MUg/ml) led to release of some metabolites such as acetate, formic
      acid, glutamate, valine, glycine, and uracil from bacteria into their
      supernatant. These findings confirm that these nanoparticles interfere with Krebs
      cycle, nucleotide, and amino acid metabolism and shows anti-H. pylori activity. 

PMID- 24104692
TI  - Angiokeratomas - When is a few too many?
AB  - Many patients have a few scattered angiokeratoma and we reassure them that this
      it is normal; however, if they are numerous, Fabry disease should be considered
      and the family history should be checked. 

PMID- 24104693
TI  - The HVTN503/Phambili HIV vaccine trial: a comparison of younger and older
      participants.
AB  - By comparing younger to older participants enrolled in a HIV vaccine efficacy
      trial, we aimed to gain insights into the inclusion of adolescents in future
      trials. This was a sub-analysis of a multisite HIV vaccine randomized clinical
      trial in South Africa, conducted January-September 2007. Motivations for trial
      enrolment, social harms, adverse events and loss to follow-up were compared
      between younger (18-20 years old) and older participants (21-35 years old). Both
      younger (n = 238) and older participants (n = 563) were equally likely to report
      enrolling for altruistic reasons. Younger females were less likely than older
      participants to join for trial reimbursement (p = 0.005), while younger males
      were more likely to enrol because the vaccine may provide protection from HIV
      acquisition (p < 0.001). There were no significant differences in the number of
      social harms reported. Compared to males over 20 years old, 18-20-year-old
      females were less likely to experience adverse events (OR = 0.1, CI 0.01-0.80)
      and no more likely to be lost to follow-up (OR = 0.7, CI 0.39-1.25), while 18-20
      year-old males were no more likely to experience adverse events (OR = 1.3, CI
      0.58-2.83) or loss to follow-up (OR = 0.8, CI 0.51-1.41). Our data support the
      inclusion of younger participants who are at risk for HIV in future HIV vaccine
      efficacy trials.

PMID- 24104694
TI  - Haemoglobin recovery among HIV-1 infected patients on zidovudine-based
      antiretroviral therapy and other regimens in north-central Nigeria.
AB  - We conducted a study to assess trends in haemoglobin recovery among HIV-infected
      patients initiated on zidovudine-based combination antiretroviral therapy (cART)
      stratified by baseline haemoglobin level. Haemoglobin data from non-pregnant
      adult patients initiating cART in rural north-central Nigeria between June 2009
      and May 2011 were analysed using a linear mixed effects model to assess the
      interaction between time, zidovudine-containing regimen and baseline haemoglobin
      level on the outcome of subsequent haemoglobin level. Best-fit curves were
      created for baseline haemoglobin in the 10th, 25th, 75th and 90th percentiles. We
      included 313 patients with 736 measures of haemoglobin in the analysis (239 on
      zidovudine and 74 on non-zidovudine-containing regimens). Median haemoglobin
      increased over time in both groups, with differences in haemoglobin response over
      time related to baseline haemoglobin levels and zidovudine use (p = 0.003). The
      groups of patients on zidovudine at the 10th and 90th percentiles had downward
      sloping curves while all other groups had upward trending haemoglobin levels.
      Although haemoglobin levels increased overall for patients on zidovudine
      containing regimens, for those in the 10th and 90th percentiles haemoglobin
      levels trended downward over time. These results have implications for decisions
      regarding when to initiate, switch from or avoid the use of zidovudine.

PMID- 24104695
TI  - Impact of fatty acids on human UDP-glucuronosyltransferase 1A1 activity and its
      expression in neonatal hyperbilirubinemia.
AB  - While breast milk has been known as a cause of neonatal hyperbilirubinemia, the
      underlying mechanism of breast milk-induced jaundice has not been clarified.
      Here, the impact of fatty acids on human UDP-glucuronosyltransferase (UGT) 1A1-
      the sole enzyme that can metabolize bilirubin--were examined. Oleic acid,
      linoleic acid, and docosahexaenoic acid (DHA) strongly inhibited UGT1A1 activity.
      Forty-eight hours after a treatment with a lower concentration of DHA (10 mg/kg),
      total bilirubin significantly increased in neonatal hUGT1 mice, which are human
      neonatal jaundice models. In contrast, treatments with higher concentrations of
      fatty acids (0.1-10 g/kg) resulted in a decrease in serum bilirubin in hUGT1
      mice. It was further demonstrated that the treatment with higher concentrations
      of fatty acids induced UGT1A1, possibly by activation of peroxisome proliferator
      activated receptors. Our data indicates that activation of peroxisome
      proliferator-activated receptors would increase UGT1A1 expression, resulting in
      reduction of serum bilirubin levels in human infants.

PMID- 24104696
TI  - The impact of abnormal muscle tone from hemiplegia on reclining wheelchair
      positioning: a sliding and pressure evaluation.
AB  - BACKGROUND: Little is known about the influence of existing muscle tone
      abnormality on the sitting posture of stroke patients in reclining wheelchairs.
      AIM: To investigate the impact of muscle tone abnormality from hemiplegia on the
      forward sliding and pressure of stroke patients while sitting in reclining
      wheelchairs. DESIGN: Experimental study. SETTING: The Assistive
      Devices/Technology Center at the Rehabilitation Department of hospital.
      POPULATION: 14 able-bodied elders and nonambulatory elderly stroke patients with
      flaccid (N.=12) or spastic hemiplegia (N.=13) participated in this study. Of the
      12 patients with flaccid hemiplegia, 8 suffered from left-sided hemiplegia and 4
      from right-sided hemiplegia. Of the 13 patients with spastic hemiplegia, 6
      suffered from left-sided hemiplegia and 7 from right-sided hemiplegia. METHODS:
      We performed 3 reclining cycles in wheelchairs with conventional seats and V
      shaped seats for each participant. The sliding along the backrest (BS) plane and
      the seat (SS) plane, mean sitting pressure (MP), and sacral peak pressure (SPP)
      of the participants were recorded. The Kruskal-Wallis test was used to compare
      the difference in BS, SS, MP, and SPP between able-bodied elders and stroke
      patients. RESULTS: The BS, SS, and SPP during repetitive reclining were generally
      greatest in flaccid hemiplegic participants, followed by spastic hemiplegic
      participants, and finally by able-bodied participants. There was no significant
      difference in MP among three subject groups on both conventional seats and V
      shaped seats in most comparisons. Able-bodied participants' buttocks tended to
      slide forward on conventional seats but backward on V-shaped seats, whereas
      hemiplegic participants' buttocks slid forward on both seat types. CONCLUSION:
      Stroke patients with flaccid hemiplegia are the most vulnerable to sacral sitting
      and higher sacral pressure in reclining wheelchairs, followed by patients with
      spastic hemiplegia. There is a difference in the displacement pattern between
      participants with normal muscle tone and those with abnormal muscle tone during
      wheelchair positioning. People who have hemiplegia with spasticity do not have
      incremental forward sliding with repetitive reclining in the same way as those
      who have a flaccid hemiplegia. CLINICAL REHABILITATION IMPACT: The findings are
      valuable for wheelchair prescription and caregiver education.

PMID- 24104697
TI  - Determinants in predicting duration of treatment in an out-patient rehabilitation
      orthopedic-traumatologic service.
AB  - BACKGROUND: Duration of rehabilitation is an important rehabilitation clinical
      outcome both from a clinical and administrative point of view. Very few studies
      have looked at predictors oftreatment duration in out-patient rehabilitation
      setting especially in patients with orthopedic-traumatologic conditions. AIM: We
      undertook a prospective study to assess treatment duration and identify variables
      predicting this outcome measure (primary outcome) and efficiency in range of
      motion and activities of daily living (secondary outcome). DESIGN: Prospective
      and observational study. SETTING: Out-patient Service for Rehabilitation.
      POPULATION: Two hundred and ten patients admitted to Out-patient Service for
      Rehabilitation of orthopedic disorders were enrolled: 94 patients had limb
      fracture (35 wrist fracture, 28 ankle fracture, 27 shoulder fracture), and 120
      and undergone elective orthopedic surgery (27 cruciate reconstruction, 93 rotator
      cuff repair). METHODS: Univariate Regression analysis was applied to analyze
      relationships among variables and length of rehabilitation while backward
      stepwise regression analysis was used to predict treatment duration. The
      independent variables were age, gender, work, type of physical therapy,
      comorbidity, pain, onset to admission interval, initial disability, initial range
      of motion percentage (ROM), and diagnosis group. RESULTS: Mean treatment duration
      was 29.7+/-15 days. Treatment duration following rotator cuff repair was
      significantly longer than that of cruciate reconstruction (P=0.005), wrist
      fracture (P<0.001), and ankle fracture (P=0.002). Treatment duration was related
      to working status, admission disability, onset to admission interval, diagnosis
      group, admission pain, and admission range of motion. In multivariate regression
      analysis, admission range of motion and onset to admission interval were the only
      independent predictors of treatment duration and efficiency in range of motion,
      while admission range of motion and admission Health Assessment Questionnaire
      were predictors of efficiency in Health Assessment Questionnaire score.
      CONCLUSION: The study highlights that rehabilitative treatment duration has
      strong relationship with admission range of motion and onset admission interval.
      CLINICAL REHABILITATION IMPACT. These findings should be useful for physicians
      for planning therapeutic measures in patients with orthopedic-traumatologic
      conditions and for managing the usual activities of an Out-patient Rehabilitative
      Service.

PMID- 24104698
TI  - Feasibility and test-retest reliability of measuring lower-limb strength in young
      children with cerebral palsy.
AB  - BACKGROUND: Quantifying leg muscle strength in young children with cerebral palsy
      (CP) is essential for identifying muscle groups for treatment and for monitoring
      progress. AIM: To study the feasibility, intratester reliability and the optimal
      test design (number of test occasions and repetitions) of measuring lower-limb
      strength with handheld dynamometry (HHD) and dynamic ankle plantar flexor
      strength with the standing heel-rise (SH) test in 3-10 year aged children with
      CP. DESIGN: Test-retest design. SETTING: Rehabilitation centre, special needs
      school for children with disabilities, and university medical centre. METHODS:
      Knee extensor, hip abductor and calf muscle strength was assessed in 20
      ambulatory children with spastic CP (3-5 years [N.=10] and 6-10 years [N.=10]) on
      two test occasions. Intraclass correlation coefficients (ICC) and Smallest
      Detectable Differences (SDD) were calculated to determine the optimal test design
      for detecting changes in strength. RESULTS: All isometric strength tests had
      acceptable SDDs (9-30%), when taking the mean values of 2-3 test occasions
      (separate days) and 2-3 repetitions. The one-leg SH test had large SDDs (40-128%
      for younger group, 23-48% for older group). CONCLUSION: Isometric strength
      (improvements) can only be measured reliably with HHD in young children with CP
      when the average values over at least 2 test occasions are taken. Reliability of
      the SH test is not sufficient for measuring individual changes in dynamic muscle
      strength in the younger children. CLINICAL REHABILITATION IMPACT: Results of this
      study can be used to determine the optimal number of test occasions and
      repetitions for reliable HHD measurements depending on expected changes, muscle
      group and age in 3-10 year old children with CP.

PMID- 24104699
TI  - Daily pilates exercise or inactivity for patients with low back pain: a clinical
      prospective observational study.
AB  - BACKGROUND: Studies have shown the effectiveness of a few weekly pilates sessions
      as helping to reduce lower back pain (LBP). However many patients fear that
      physical activity can actually make the pain and disability worse. DESIGN: We
      carried out this observational prospective clinical study to look at the effects
      that taking part in daily pilates has one on side and on the other the effects of
      LBP management without physical exercise. SETTING: The volunteers who
      participated in this study were recruited from among some local cultural
      associations. POPULATION: Patients affected by LBP were evaluated. METHODS: The
      subjects were 60 volunteers (27 males and 33 females) with a mean age of 51.2
      years who had chronic low back pain (CLBP). They were allocated to pilates group
      (N.=30) or inactivity control group (N.=30). The pilates group performed one-hour
      lesson of pilates exercise, 5 lessons per week during the following 6 months. The
      inactivity group continued with their normal daily activities. The Roland-Morris
      Disability, the Oswestry, the SF-36 and the Spinal Functional Sort Questionaries
      of all subjects were measured at the baseline (T1) and at 6 months (T2). RESULTS:
      At T2 improvements were observed in the pilates group with increases in physical
      and social functioning, general health and vitality (P<0.05) and decreases in
      disability and pain (P<0.05). The inactivity group showed worsening in the same
      measures at T2. CONCLUSION: We found an important improvement of pain, disability
      and physical and psychological perception of health in individuals who did the
      daily sessions of pilates. CLINICAL REHABILITATION IMPACT: Some authors
      underlined the possible risk of a lack of adherence to an exercise program at
      home. This study suggests that a daily pilates program is effective for the
      management of CLBP. On the other hand, the inactivity contributes to further
      worsening, inducing a vicious cycle in which pain and physical activity
      intolerance follow each other.

PMID- 24104700
TI  - Depression and anxiety levels in mothers of children with cerebral palsy: a
      controlled study.
AB  - BACKGROUND: Studies investigating depression and anxiety levels in mothers of
      children with CP and related factors are limited, and controversial findings are
      reported in these studies. AIM: The study was aimed to determine depression and
      anxiety levels in mothers of children with cerebral palsy (CP) and to define
      factors related to depression and anxiety levels. DESIGN: A descriptive study.
      SETTING: Outpatient physical medicine and rehabilitation clinic of an education
      and research hospital. POPULATION: The study was composed of two groups: group 1,
      116 mothers of children with CP and group 2, 114 mothers of healthy children.
      METHODS: Mothers of children with spastic-type CP were included into group 1.
      Functional levels in children with CP were investigated with The Gross Motor
      Function Classification System (GMFCS). Depression levels of mothers in both
      groups were assessed with Beck Depression Inventory (BDI), and anxiety levels
      with Beck Anxiety Inventory (BAI). RESULTS: BDI and BAI scores were statistically
      and significantly higher in group 1, compared to group 2. Among mothers in group
      1, a positive correlation was determined between GMFCS score, and depression and
      anxiety levels. However, no correlation was detected between depression and
      anxiety levels, and body involvement of CP, education status, age and economic
      level among patients. In logistic regression analysis, the most significant risk
      factors of depressive symptoms were detected to be GMFCS score and speech
      defects. CONCLUSION: Our findings indicate that depression and anxiety levels of
      mothers with CP children are higher than those with healthy children and
      associated with speech defects and functional disability levels in children with
      CP. Healthcare professionals should take into account that depression and anxiety
      levels may be higher in mothers of children with CP. CLINICAL REHABILITATION
      IMPACT: For an effective rehabilitation program related to children with CP,
      depression and anxiety levels in mothers of such children should be taken into
      account, and mothers should closely be followed and if necessary, psychologically
      supported.

PMID- 24104701
TI  - A red fluorescence 'off-on' molecular switch for selective detection of Al3+,
      Fe3+ and Cr3+: experimental and theoretical studies along with living cell
      imaging.
AB  - A spirobenzopyran-quinoline (SBPQ) based sensor was synthesized which selectively
      detects trivalent ions viz. Al(3+), Fe(3+) and Cr(3+) through a fluorescence turn
      on signal in the red region (~675 nm) with the detection limit in the order of
      10(-8) M. The potentiality of the probe was confirmed by employing it for
      fluorescence bio-imaging with Al(3+) in three different types of live-cells.

PMID- 24104702
TI  - Possibility of cross-species/subtype reassortments in influenza A viruses: an
      analysis of nonstructural protein variations.
AB  - The reassortment of genetic segments from different host species and from
      different subtypes of influenza A viruses occurs frequently, which may generate
      new strains causing flu epidemic or pandemic. However, the underlined mechanisms
      of reassortment were less addressed from the viewpoint of protein variations.
      Recently, we used the amino-acid pair predictability as an indicator to convert
      eight types of influenza A virus proteins into predictable portion of amino-acid
      pairs, and then applied the models I and II ANOVA to estimate their differences
      in terms of subtypes and host species. In order to get a full picture, 2729 and
      1063 non-structural 1 and 2 proteins of influenza A viruses were analyzed in this
      study. The results are consistent with those obtained from hemagglutinin,
      neuraminidase, nucleoprotein, polymerase acidic protein, polymerase basic
      proteins 1 and 2, and matrix proteins 1 and 2, indicating that inter
      species/subtypes variations are smaller than intra-species/subtype ones. Our
      findings provide statistical evidence that can partially explains why cross
      subtype mutation and cross-species infection easily occur during co-infecting of
      different strains. 

PMID- 24104703
TI  - Opioid requirement, opioid receptor expression, and clinical outcomes in patients
      with advanced prostate cancer.
AB  - BACKGROUND: Preclinical studies show that opioids stimulate angiogenesis and
      tumor progression through the mu opioid receptor (MOR). Although MOR is
      overexpressed in several human malignancies, the effect of chronic opioid
      requirement on cancer progression or survival has not been examined in humans.
      METHODS: We performed a retrospective analysis on 113 patients identified in the
      Minneapolis VA Tumor Registry (test cohort) and 480 patients from the national VA
      Central Cancer Registry (validation cohort) who had been diagnosed with stage IV
      prostate cancer between 1995 and 2010 to examine whether MOR expression or opioid
      requirement is associated with disease progression and survival. All opioids were
      converted to oral morphine equivalents for comparison. Laser scanning confocal
      microscopy was used to analyze MOR immunoreactivity in prostate cancer biopsies.
      The effects of variables on outcomes were analyzed in univariable and
      multivariable models. RESULTS: In patients with metastatic prostate cancer, MOR
      expression and opioid requirement were independently associated with inferior
      progression-free survival (hazard ratio [HR] 1.65, 95% confidence interval [CI]
      1.33-2.07, P<.001 and HR 1.08, 95% CI 1.03-1.13, P<.001, respectively) and
      overall survival (HR 1.55, 95% CI 1.20-1.99, P<.001 and HR 1.05, 95% CI 1.00
      1.10, P = .031, respectively). The validation cohort confirmed that increasing
      opioid requirement was associated with worse overall survival (HR 1.005, 95% CI
      1.002-1.008, P = .001). CONCLUSION: Higher MOR expression and greater opioid
      requirement are associated with shorter progression-free survival and overall
      survival in patients with metastatic prostate cancer. Nevertheless, clinical
      practice should not be changed until prospective randomized trials show that
      opioid use is associated with inferior clinical outcomes, and that abrogation of
      the peripheral activities of opioids ameliorates this effect.

PMID- 24104705
TI  - Conservative treatment modalities in retinoblastoma.
AB  - Retinoblastoma is the most common primary intraocular malignancy of childhood. A
      potentially curable cancer, its treatment has improved significantly over the
      last few decades. The purpose of this article is to review the literature on
      various conservative treatment modalities available for the treatment of
      retinoblastoma and their effectiveness, when used alone or in combination.
      Pubmed, Medline, Embase, and the Cochrane library were searched through 2012 for
      published peer reviewed data on conservative treatment modalities for
      retinoblastoma. Various studies show that while enucleation remains the standard
      of care for advanced intraocular tumors, conservative modalities that can result
      in globe salvage and preservation of useful vision are being increasingly
      employed. Such modalities include systemic chemotherapy, focal consolidation with
      transpupillary thermotherapy, laser photocoagulation and cryotherapy, plaque
      brachytherapy, and delivery of local chemotherapy using subconjunctival, sub
      tenon, or intra-arterial routes. When used alone or in combination, these
      treatment modalities can help in avoidance of external beam radiotherapy or
      enucleation, thus reducing the potential for long-term side effects, while
      salvaging useful vision. Radioactive plaque brachytherapy has an established role
      in selected patients with intraocular retinoblastoma. Local injections of
      chemotherapeutic agents via the sub-tenon or sub-conjunctival route have been
      used with varying degrees of success, usually as an adjunct to systemic
      chemotherapy. Intra-arterial ophthalmic artery delivery of melphalan has shown
      promising results. It is important to recognize that today, several treatment
      options are available that can obviate the need for enucleation, and cure the
      cancer with preservation of functional vision. A thorough knowledge and
      understanding of these conservative treatment modalities is essential for
      appropriate management. 

PMID- 24104704
TI  - Anti-vascular endothelial growth factor in age-related macular degeneration:
      puzzle or a silent beginning!

PMID- 24104706
TI  - Demographic and clinical profile of vernal keratoconjunctivitis at a tertiary eye
      care center in India.
AB  - PURPOSE: To study the demographic and clinical profile of patients with vernal
      keratoconjunctivitis (VKC) at a tertiary eye care center in India. MATERIALS AND
      METHODS: Retrospective chart analysis of 468 patients of VKC seen from January
      2006 to December 2006. RESULTS: Mean age at presentation was 12 years. Majority
      of the patients had mixed pattern disease (72%). Chronic perennial disease was
      seen in 36% patients. Personal or family history of allergies was noted in 5%
      patients. Severe disease based on clinical grading was present in 37% patients.
      Moderate to severe vision loss was seen in 12% of total population. Persistent
      disease beyond 20 years of age was found in 12% patients. VKC-related
      complications such as corneal scarring (11%), shield ulcer (3%), keratoconus
      (6%), and limbal stem cell deficiency (1.2%) were seen. Treatment-related
      complications like corticosteroid-induced cataract and glaucoma were seen in 6%
      and 4% of patients, respectively. CONCLUSION: Clinical pattern of VKC seen in the
      tropical climate of India is essentially similar to that seen in other tropical
      countries. Few distinct features that we noted represent chronic perennial
      disease, low association with atopy, and higher propensity for disease and
      treatment-related complications.

PMID- 24104707
TI  - Intravitreal anti-VEGF monotherapy for thick submacular hemorrhage of less than 1
      week duration secondary to neovascular age-related macular degeneration.
AB  - AIM: To investigate the role of anti-VEGF monotherapy in patients with thick
      submacular hemorrhage (SMH) of <= 1 week duration secondary to neovascular age
      related macular degeneration (N-AMD). MATERIALS AND METHODS: A retrospective
      chart review of 14 eyes of 14 patients presenting with acute decrease in central
      vision of <= 1 week duration secondary to a thick SMH measuring >= 2 MPS disk
      areas from N-AMD was performed. Intravitreal injections of bevacizumab 1.25 mg
      (13 eyes) or ranibizumab 0.5 mg (1 eye) were given monthly until resolution of
      SMH and less frequently thereafter, based on treat-and-extend approach utilizing
      spectral domain optical coherence tomography (SDOCT). Patients with follow-up of
      >= 6 months were included. RESULTS: Patients presented after a median of 4 (range
      1-7) days from the onset of SMH. Mean lesion size was 27.9 mm2 (range 5.47-100,
      median 15), with blood comprising 77-98% of the lesion. Presenting visual acuity
      (VA) ranged from 20/60 to hand motions (median 20/200). Patients received a mean
      of 11.4 (range 5-20) injections over 18.4 (range 7-50) months. SMH resolved in
      all eyes in a mean of 4.8 (range 2-8) months. At 6 months follow-up, mean VA gain
      was -0.54 logMAR (range: -1.5 to +1, Snellen range 20/25-20/400, median 20/100, P
      = 0.0037), with 11 gaining >= 0.2 logMAR. Mean change in VA from baseline at
      final follow-up was -0.58 logMAR (range -1.6 to +1, Snellen range 20/30-20/400,
      median 20/60; P = 0.0022). CONCLUSION: A good anatomical and visual outcome can
      be accomplished in patients with thick SMH secondary to N-AMD treated with anti
      VEGF monotherapy within 1 week.

PMID- 24104708
TI  - Causes and characteristics of work-related eye injuries in western Turkey.
AB  - OBJECTIVES: To analyze descriptive data and characteristics of work-related eye
      injuries (WREI) admitted into the emergency department (ED) and obtain
      information to utilize in planning measures to prevent WREI. MATERIALS AND
      METHODS: This prospective study recruited patients with WREI admitted to the
      center in the two-year study period. Only the casualties occurred at the
      workplace and while working constituted the sample. The data were collected via
      face-to-face contact in the ED. RESULTS: Males comprised the majority of the
      sample (95.3%, n = 778) and mean age of the patients was 28.1 +/- 6.5 (range: 15
      54) with the biggest percentage in between 25 and 34 years of age (46.2%, n =
      377). Most patients were working in the metal and machinery sectors (66.4%, n =
      542). Nearly half of the patients had less than 1 year of experience (50.4%, n =
      411). The most common mechanism of WREI was noted to be exposures to welding
      light (26.9%, n = 219), followed by drilling/cutting injuries (21.1%, n = 172).
      "Carelessness" and "hurrying up" were the most commonly reported causes of WREIs
      among 'worker-related causes' (21.4% and 16.1%, respectively). Lack of protective
      measures ranked the highest among workplace-related causes (18.7%, n = 207).
      CONCLUSIONS: Programs to increase awareness on workplace safety and sound
      preventive strategies for both parties-employers and employees are to be pursued.
      Occupational safety efforts should include training on workplace eye safety and
      campaigns to raise knowledgeability on this disease among workers.

PMID- 24104709
TI  - Prognostic factors for open globe injuries and correlation of ocular trauma score
      at a tertiary referral eye care centre in Singapore.
AB  - OBJECTIVE: To evaluate the factors influencing final vision outcome after
      surgical repair of open globe injuries and to correlate the Ocular trauma score.
      MATERIALS AND METHODS: Retrospective case analysis of patients with open globe
      injuries at a tertiary referral eye care centre in Singapore was performed. Pre
      operative factors affecting final vision outcome in patients with open globe
      injury and correlation of ocular trauma score in our study with international
      ocular trauma scoring system was performed. RESULTS: Case records of 172 eyes
      with open globe injury were analyzed. Mean age was 36. 67 years. Mean follow up
      was 12.26 m. Males were pre-dominantly affected. Initial visual acuity was >=
      20/40, 20/50 < 20/200, 20/200- CF, HM- PL and NLP in 24 (14%), 39 (22.7%), 16
      (9.3%), 66 (38.4%) and 27 (15.7%) eyes respectively. Final visual acuity was <=
      20/40, 20/50 < 20/200, 20/200- 1/200, HM- PL and NLP in 76 (44.2%), 28 (16.3%),
      11 (6.4%), 30 (17.4%) and 27 (15.7%) eyes respectively. Ocular trauma score in
      our study correlates with international ocular trauma scoring system. CONCLUSION:
      The present study showed pre-operative variables such as mode of injury, pre
      operative visual acuity, traumatic cataract, hyphaema, relative afferent
      papillary defect, vitreous lossand vitreous hemorrhage to be adversely affecting
      the final vision outcome. Our study showed a good synchrony with international
      ocular trauma score (OTS) and based on this study we were able to validate
      application of OTS in Singapore population. Recognizing these factors can help
      the surgeon in evidence based counseling.

PMID- 24104710
TI  - Foveal slope measurements in subjects with high-risk of age-related macular
      degeneration.
AB  - BACKGROUND: Recent reports indicated that the slope of the foveal depression
      influences the macular pigment (MP) spatial profile. MP has been shown to confer
      possible protection against age-related macular degeneration (ARMD) because of
      its antioxidant properties. AIMS: To study the configuration of foveal slope and
      the foveal thickness in fellow eyes of subjects with unilateral neovascular ARMD.
      SETTINGS AND DESIGN: Case-control series. MATERIALS AND METHODS: The study
      population consisted of 30 cases aged >50, who had unilateral choroidal
      neovascular membrane (CNVM) or disciform scar in the fellow eye and 29 controls
      aged >50, who had no sign of ARMD in the either eye. Using spectral-domain
      optical coherence tomography, foveal thickness at different locations including
      the central subfield foveal thickness (CSFT) was noted. The foveal slopes were
      calculated in the six radial scans (between 0.25 degrees  and 1 degrees  retinal
      eccentricity) as well as the 3D scan. RESULTS: Cases had a significantly higher
      CSFT when compared to controls (215.1 +/- 36.19 MU vs. 193.0 +/- 17.38 MU, P =
      0.004). On the 3D scan, the cases had shallower superior (cases 1.32 +/- 0.32 vs.
      controls 1.45 +/- 0.13, P = 0.04) and temporal slopes (cases 1.27 +/- 0.21 vs.
      controls 1.39 +/- 0.12, P = 0.01) in comparison to the controls. CONCLUSIONS: We
      noted a shallower superior and temporal foveal slope and a higher CSFT in the
      fellow eyes of subjects with a unilateral neovascular ARMD. Prospective studies
      observing the development of CNVM in subjects with altered foveal slope might
      provide more information on this optical coherence tomography finding.

PMID- 24104711
TI  - Donor disc attachment assessment with intraoperative spectral optical coherence
      tomography during descemet stripping automated endothelial keratoplasty.
AB  - Optical coherence tomography has already been proven to be useful for pre- and
      post-surgical anterior eye segment assessment, especially in lamellar
      keratoplasty procedures. There is no evidence for intraoperative usefulness of
      optical coherence tomography (OCT). We present a case report of the
      intraoperative donor disc attachment assessment with spectral-domain optical
      coherence tomography in case of Descemet stripping automated endothelial
      keratoplasty (DSAEK) surgery combined with corneal incisions. The effectiveness
      of the performed corneal stab incisions was visualized directly by OCT scan
      analysis. OCT assisted DSAEK allows the assessment of the accuracy of the
      Descemet stripping and donor disc attachment. 

PMID- 24104712
TI  - Bilateral central serous chorioretinopathy with retinal pigment epithelium tears
      following epidural steroid injection.
AB  - The cause of central serous chorioretinopathy (CSC) is mostly idiopathic. Other
      cause such as stressful event or use of corticosteroid has been associated with
      severe form of CSC. Atypical presentation of CSC has widespread degeneration of
      retinal pigment epithelium (RPE) or bullous retinal detachment. In this report,
      we describe a case of bilateral CSC with RPE tear after epidural steroid
      injection. 

PMID- 24104713
TI  - An unusual case of self-inflicted multiple needles injuries to eye.
AB  - Self-inflicted eye injuries among psychiatric patients are rare but important
      group of ophthalmic conditions that require close cooperation between different
      medical specialties to ensure optimum care of the severely disturbed patient.
      They have been associated with a variety of disorders, including paranoid
      schizophrenia, drug-induced psychosis, obsessive-compulsive disorder, depression,
      mental retardation, and ritualistic behavior. It has been described in both
      adults and children, but occurs most commonly in young adults with acute or
      chronic psychoses. 

PMID- 24104714
TI  - Peeling and aspiration of elschnig pearls! An effective alternative to Nd:YAG
      laser capsulotomy!
AB  - To evaluate the efficacy of peeling and aspiration of Elschnig pearls.
      Retrospective study in a medical college hospital. Records of 217 eyes which
      underwent surgical peeling and aspiration for membranous PCO between 2006 and
      2009, was reviewed. Peeling and aspiration was fashioned with a blunt tipped 20G
      cannula after stabilizing anterior chamber with anterior chamber maintainer. Post
      operative vision and complications were analyzed. Mc Nemar and Chi square tests.
      The mean age was 56.84 years. 85.71% patients achieved best corrected visual
      acuity (BCVA) of 20/20 at 3 m. Recurrence of pearls, uveitis and cystoid macular
      edema were the most common causes of reduced vision. Peeling and aspiration of
      pearls seem to be a viable alternative to Neodymium yttrium garner aluminium (Nd:
      YAG) laser capsulotomy for membranous PCO. 

PMID- 24104715
TI  - Reverse masquerade syndrome: fungal adnexal infection mimicking carcinoma in a
      HIV-positive patient.
AB  - A known HIV-positive male patient presented with a rapidly progressive ulcerative
      lesion involving the conjunctiva, lids, and anterior orbit along with a decrease
      in vision in the right eye. He was on anti retro-viral and anti-tubercular
      therapy. In view of the clinical features, our provisional clinical diagnosis was
      a malignant lesion of the eyelid with orbital involvement, possibly squamous cell
      carcinoma. However, incisional biopsy revealed absence of malignant cells. On
      Gomori Methenamine Silver staining, plenty of fungal filaments were seen, which
      was confirmed by culture as Candida albicans. Hence, it turned out to be a case
      of fungal adnexal infection mimicking carcinoma in a HIV-positive patient. The
      patient responded well to systemic anti-fungals. 

PMID- 24104716
TI  - Growth of Scytalidium sp. in a counterfeit bevacizumab bottle.
AB  - After drawing a dose from an closed bevacizumab (Avastin) bottle, a fungus-like
      foreign body was observed inside. Samples from the vial were cultured in
      Sabouraud Emmons media. Growth of multiple light brown colonies with dark pigment
      was observed after 10 days. The species was identified as Scytalidium sp.Vial,
      analysis reported that the seal was lacking proper identification measures and
      that the label, batch number and expiry date did not correspond to a genuine
      product. Chemical analysis showed no protein, but 3% of polyethylene glycol,
      citrate and ethanol. Counterfeit bevacizumab is a real situation that poses a
      significant risk for ophthalmology and oncology patients. The medical community
      should be aware of this situation in order to enforce adequate preventive
      measures. 

PMID- 24104717
TI  - Comparison of efficiency of intravitreal ceftazidime and intravitreal cefepime in
      the treatment of experimental Pseudomonas aeruginosa endophthalmitis.
AB  - In this study, we evaluated the efficiency of cefepime in the treatment of
      experimental Pseudomonas aeruginosa endophthalmitis. We compared the findings
      with the standard dose of ceftazidime (1 mg/0.1 ml). Thirty-six New-Zealand White
      rabbits were divided into 6 equal groups and were treated with different methods
      (Group 1 = sham, Group 2 = 0.5 mg/0.1 ml cefepime, Group 3 = 1 mg/0.1 ml
      cefepime, Group 4 = 2 mg/0.1 ml cefepime, Group 5 = 1 mg/0.1 ml ceftazidime,
      Group 6 = control). The eyes of rabbits in each group were examined clinically on
      1 st , 3 rd , and 6 th day of the experiment. At 6 th day, 0.1 ml vitreous humor
      aspirates were obtained and plated for quantification on the blood agar and the
      results were expressed as colony-forming unit/ml. Subsequently, the eyeballs were
      enucleated and the histopathological evaluation was performed. Our findings
      denoted beneficial effects of cefepime in treatment groups (especially, in Groups
      3 and 4). Intravitreal cefepime may be an alternative drug in the treatment of P.
      aeruginosa endophthalmitis. 

PMID- 24104718
TI  - One day wonder: fast resolution of macular edema following intravitreal
      ranibizumab in retinal venous occlusions.
AB  - Macular edema is a significant cause of vision loss in patients with central
      retinal vein occlusions and branch retinal vein occlusions. Vascular endothelial
      growth factor (VEGF) appears to be a key factor in the pathogenesis of this
      disease. Anti-VEGF therapy, such as intravitreal ranibizumab provides an
      effective treatment against vision-threatening macular edema. We report three
      patients of retinal vein occlusion with macular edema who demonstrated overnight
      resolution of macular edema following treatment with intravitreal ranibizumab
      (0.5 mg). 3D optical coherence tomography (Optovue) was used as a tool for
      comparison of the macular thickness before and after treatment. The significant
      reductions in the central foveal thickness demonstrated in these patients one
      night after intravitreal injections could have significant influence on modifying
      current treatment protocols. Early treatment of macular edema related to retinal
      venous occlusive disease with anti-VEGF injections could result in faster visual
      rehabilitation in these patients. 

PMID- 24104719
TI  - SD-OCT based management of traumatic sub-macular hemorrhage-Our experience.

PMID- 24104720
TI  - Eat the pie or imbibe the ribbon: an epochal moment at the crossroads of
      mechanized cataract surgery.

PMID- 24104721
TI  - Structural-functional dissociation in glaucoma: an attempt to end controversy.

PMID- 24104722
TI  - Incidence of pupillary involvement, course of anisocoria and ophthalmoplegia in
      diabetic Oculomotor nerve palsy.

PMID- 24104723
TI  - Factors having implications on re-retinal detachments after silicone oil removal.

PMID- 24104724
TI  - Pharmaceutical analysis by solid-substrate electrospray ionization mass
      spectrometry with wooden tips.
AB  - Electrospray ionization (ESI) using wooden tips as solid substrates allows direct
      ionization of various samples and their simple and efficient analyses by mass
      spectrometry (MS). In this study, wooden-tip ESI-MS was used for pharmaceutical
      analysis. A wide variety of active components present in pharmaceuticals with
      forms of tablets, capsules, granules, dry suspensions, suspensions, drops, and
      oral liquids, etc., were all successfully ionized directly for mass spectrometric
      analysis. Trace degradation products were also sensitively detected using wooden
      tip ESI-MS. This strategy was extended to construct chemical fingerprints of
      herbal products containing complex and unknown components, and the fingerprints
      provided valuable information for their quality assessment and origin tracing.
      Our experimental data demonstrated that wooden-tip ESI-MS is a useful tool for
      rapid pharmaceutical analysis, with high sensitivity and wide applicability,
      showing promising perspectives for quality assessment and control,
      authentication, and origin tracing of pharmaceuticals. 

PMID- 24104725
TI  - Loss of molar occlusion and mandibular morphology in adults in an ancient human
      population consuming a coarse diet.
AB  - The purpose of the study is to investigate the link between number of molar teeth
      retained in occlusion and mandibular morphology in adults in an ancient, high
      dental wear human population. The study material comprises skeletons from
      Mediaeval Wharram Percy, England (N = 50 female, 69 male adults). It was
      hypothesized that adults retaining fewer occluding molars would show reduction in
      mandibular dimensions, particularly in the ascending ramus and gonial regions
      where the main muscles of mastication have their insertions. Molar occlusal
      status is assessed using the concept of functional units. Mandibular morphology
      is assessed using a suite of ten linear measurements plus the mandibular angle.
      Results show no evidence for any association between number of molars retained in
      occlusion and mandibular angle. There was an association between mandibular size
      and number of molars retained in occlusion, with smaller mandibular dimensions in
      those retaining fewer occluding molars. Some measurements were affected more than
      others so that there was also some shape alteration. Alteration of mandibular
      dimensions was more clearly demonstrable in females than in males. Only in
      females could significant reduction in the ascending ramus and gonial regions be
      demonstrated. Reasons for the apparent difference in response to loss of molar
      occlusion between male and female mandibles are unclear, but sex differences in
      bony metabolism mediated by hormonal factors may be implicated. Results suggest
      that care should be exercised when including mandibles from individuals showing
      loss of molar occlusion in morphological studies.

PMID- 24104726
TI  - Low-dimensional dynamics of resting-state cortical activity.
AB  - Endogenous brain activity supports spontaneous human thought and shapes
      perception and behavior. Connectivity-based analyses of endogenous, or resting
      state, functional magnetic resonance imaging (fMRI) data have revealed the
      existence of a small number of robust networks which have a rich spatial
      structure. Yet the temporal information within fMRI data is limited, motivating
      the complementary analysis of electrophysiological recordings such as
      electroencephalography (EEG). Here we provide a novel method based on
      multivariate time-frequency interdependence to reconstruct the principal resting
      state network dynamics in human EEG data. The stability of network expression
      across subjects is assessed using resampling techniques. We report the presence
      of seven robust networks, with distinct topographic organizations and high
      frequency (~ 5-45 Hz) fingerprints, nested within slow temporal sequences that
      build up and decay over several orders of magnitude. Interestingly, all seven
      networks are expressed concurrently during these slow dynamics, although there is
      a temporal asymmetry in the pattern of their formation and dissolution. These
      analyses uncover the complex temporal character of endogenous cortical
      fluctuations and, in particular, offer an opportunity to reconstruct the low
      dimensional linear subspace in which they unfold.

PMID- 24104727
TI  - Effects of temperature on the dynamics of the LacI-TetR-CI repressilator.
AB  - We studied the behaviour of the repressilator at 28  degrees C, 30  degrees C, 33
      degrees C, and 37  degrees C. From the fluorescence in each cell over time, we
      determined the period of oscillations, the functionality (fraction of cells
      exhibiting oscillations) and the robustness (fraction of expected oscillations
      that occur) of this circuit. We show that the oscillatory dynamics differs with
      temperature. Functionality is maximized at 30  degrees C. Robustness decreases
      beyond 30  degrees C, as most cells exhibit 'failed' oscillations. These failures
      cause the distribution of periods to become bimodal, with an 'apparent period'
      that is minimal at 30  degrees C, while the true period decreases with increasing
      temperature. Based on previous studies, we hypothesized that the failures are due
      to a loss of functionality of one protein of the repressilator, CI. To test this,
      we studied the kinetics of a genetic switch, formed by the proteins CI and Cro,
      whose expression is controlled by PRM and PR, respectively. By probing the
      activity of PRM by in vivo detection of MS2-GFP tagged RNA, we find that, beyond
      30  degrees C, the production of the CI-coding RNA changes from sub-Poissonian to
      super-Poissonian. Given this, we suggest that the decrease in efficiency of CI as
      a repressor with temperature hinders the robustness of the repressilator beyond
      30  degrees C. We conclude that the repressilator is sensitive but not robust to
      temperature. Replacing CI for a less temperature-dependent protein should enhance
      robustness. 

PMID- 24104728
TI  - The best laid plans: community-based natural resource management (CBNRM) group
      capacity and planning success.
AB  - As community-based natural resource management (CBNRM) increases in popularity,
      the question of the capacity of such groups to successfully manage natural
      resources becomes increasingly relevant. However, few studies have quantifiably
      analyzed how the amount or type of capacity in a CBNRM organization directly
      affects the outputs or the environmental outcomes produced. This paucity of
      research exists in part due to the diversity of indicators for CBNRM group
      capacity, as well as the ensuing debate over how to best define and measure
      success in CBNRM initiatives. Although concrete outputs vary widely, many efforts
      center on creating natural resource management plans (RMPs). The primary
      objective of our research was to explore the link between capacity and RMP
      implementation success, as perceived by practitioners among CBNRM groups across
      Illinois. A short online survey was constructed, utilizing findings from focus
      groups in combination with an extensive literature review, to measure CBNRM
      participants' (n = 190) perceptions of 10 key capacity indicators and RMP
      implementation success. Results show that capacity perceptions varied
      significantly among respondents in low, moderate, and high RMP implementation
      success groups, and that group capacity was predictive of the degree of perceived
      RMP implementation success. Further, our findings suggest that bonding social
      capital and outreach are crucial in predicting low versus moderate RMP success,
      while leadership, motivation, and vision best distinguish the moderately
      successful and highly successful groups.

PMID- 24104729
TI  - The role of ownership in environmental performance: evidence from coalbed methane
      development.
AB  - One way coalbed methane production differs from traditional oil and gas
      extraction is in the large quantities of produced water. This water must be
      disposed of for production to occur. Surface discharge has proven to be a low
      cost alternative; regulations are in place to protect surface water quality. This
      paper investigates the effects of alternative ownership regimes on regulatory
      compliance. A unique dataset linking coalbed methane wells in Wyoming to water
      disposal permit violations is used to explore differences in environmental
      performance across severed and unified minerals. Empirical analysis of these data
      suggest that ownership does impact environmental compliance behavior. Most
      violations occur on split estate. Federal split estate wells have more severe
      violations, though not necessarily more of them. Federal unified wells performed
      best, with fewer and less serious violations. Wells on private land have more,
      though not necessarily more severe, violations. These results suggest some room
      for policy proposals accounting for alternative ownership regimes. 

PMID- 24104730
TI  - In need of an upgrade.

PMID- 24104731
TI  - Amgen swallows Onyx whole.

PMID- 24104733
TI  - China clampdown on GSK linked to drug costs.

PMID- 24104735
TI  - Scripps boosts research coffers by selling reagents to Sigma-Aldrich.

PMID- 24104737
TI  - Neurodevice startups target peripheral nervous system.

PMID- 24104742
TI  - From the bottom of a DNA cocktail glass.

PMID- 24104740
TI  - Mars collaborates to sequence Africa's neglected food crops.

PMID- 24104744
TI  - India's onslaught on drug patents continues.

PMID- 24104745
TI  - Big oil turns on biofuels.

PMID- 24104746
TI  - Top US universities, institutes for life sciences in 2012.

PMID- 24104747
TI  - What is the point of large-scale collections of human induced pluripotent stem
      cells?

PMID- 24104748
TI  - A proposal to use gamete cycling in vitro to improve crops and livestock.

PMID- 24104749
TI  - The regulatory landscape for actively personalized cancer immunotherapies.

PMID- 24104750
TI  - The value of non-human primates in the development of monoclonal antibodies.

PMID- 24104751
TI  - DREAMing of a patent-free human genome for clinical sequencing.

PMID- 24104753
TI  - Phospho-specific antibodies by design.

PMID- 24104754
TI  - Modified RNA kick-starts cardiac repair.

PMID- 24104755
TI  - Differences that matter in cancer genomics.

PMID- 24104757
TI  - The anatomy of successful computational biology software.

PMID- 24104758
TI  - The missing piece to changing the university culture.

PMID- 24104760
TI  - What is patient adherence? A terminology overview.
AB  - It is well known that patient adherence to appropriately prescribed medications
      is essential for treatment efficacy and positive therapeutic outcomes. It is also
      understood that patients who are prescribed medications do not necessarily take
      them as prescribed. Indeed, variation in patients' medication-taking is an age
      old conundrum which remains the focus of much interest amongst researchers and
      clinicians owing to its far-reaching consequences. Despite the extensive
      adherence-related research over the last four decades and a recent surge in this
      field, there remains a lack of uniformity in the terminology used to describe
      adherence and its related concepts. In turn, it is often difficult to conduct
      comparisons between adherence-related studies, which may be associated with the
      non-cumulative nature of work in this field. The purpose of this commentary is to
      provide an overview of key terminology relating to the field of adherence
      research. 

PMID- 24104761
TI  - Treatment of multiple sclerosis in Germany: an analysis based on claims data of
      more than 30,000 patients.
AB  - BACKGROUND: Multiple sclerosis (MS) is an incurable disease of the central
      nervous system. In addition to symptomatic treatment, immunomodulatory and
      immunosuppressant agents are used to prevent attacks and to influence the course
      of disease. OBJECTIVE: The goal of this study was to assess the drug use of MS
      patients in outpatient care considering gender-related and regional differences.
      SETTING: We analyzed outpatient claims data of the single largest German health
      insurance fund (about 9 million insurants) for the year 2010. METHOD: Patients
      with MS were identified by outpatient ICD-10-GM-diagnosis code 'G35'. All age
      groups were included. MS-specific drug use was analysed for those patients,
      considering regional and gender-related differences in specific drug
      prescriptions. MAIN OUTCOME MEASURE: Prescription rates for symptomatic
      treatment, relapse treatment and disease-modifying treatment. RESULTS: 31,248
      patients with a diagnosis of MS were identified (0.35 % of all insurants). Their
      mean age was 50.4 +/- 14.1 years, 77.7 % of them were female. 37.6 % of the
      included patients were treated with disease-modifying drugs, 23.4 % got
      prescriptions for corticosteroids, drugs of choice for relapse therapy, and 63.1
      % received symptomatic treatment as defined in the study. Women with MS were
      prescribed significantly more non-steroidal anti-inflammatory drugs, urinary
      antispasmodics, antidepressants, tranquilizer and hypnotic drugs. Regional
      variations were also found, with highest usage of disease-modifying drugs in
      eastern regions of Germany. CONCLUSION: This study gives an insight into the
      treatment of MS in daily practice by using the claims data of a large health
      insurance company. The prescription rate for disease modifying drugs was
      relatively low suggesting that early treatment was not routine practice.
      Furthermore, the results indicated that women with MS were more likely to receive
      treatment for psychiatric symptoms and pain.

PMID- 24104762
TI  - Drug utilization pattern and cost for the treatment of severe sepsis and septic
      shock in critically ill cancer patients.
AB  - BACKGROUND: Cancer patients are at high risk for developing sepsis. To our
      knowledge, there are no studies that evaluated the type of medications utilized
      and the associated cost in cancer patients with severe sepsis and septic shock.
      OBJECTIVE: To describe the drug utilization pattern and drug cost in the
      treatment of cancer patients with severe sepsis and septic shock. SETTING: 12-bed
      medical/surgical intensive care unit (ICU) of a comprehensive teaching cancer
      center. METHODS: A retrospective cohort study of cancer patients with severe
      sepsis or septic shock who were treated in the ICU between January and December,
      2010. The ICU sepsis database was used to identify patients. The patient
      demographics and characteristics were recorded. In addition, the number and type
      of prescribed medications, total cost for each medication, type of infection, and
      culture results were determined. MAIN OUTCOME MEASURE: The main outcomes were the
      type of medication classes utilized and the cost of the medications. RESULTS:
      During the study period, 116 cases were identified. Upon presentation, the mean
      Acute Physiology and Chronic Health Evaluation II (APACHE II) score was 21.8 (SD
      +/- 7.8), 30 (25.9 %) patients had neutropenia, and 94 (81 %) had positive
      cultures. The total cost of the medications prescribed for this cohort of
      patients was 291,030 Euro. The mean number of medications prescribed per patient
      and the mean total cost per patient were 11.7 (SD +/- 4.7) and 2,509 Euro (SD +/-
      2,844), respectively. The most commonly prescribed medication classes were acid
      suppressive therapy, glycopeptides, penicillins/cephalosporins and vasopressors
      prescribed in 113 (97 %), 104 (89.7 %), 103 (88.9 %), and 102 (88 %) patients,
      respectively. The highest medication costs were associated with antifungals (mean
      1,288 Euro/patient) and colony stimulating factors (mean 829 Euro/patient),
      prescribed in 55 (47.4 %) and 37 (31.9 %) patients, respectively. Medication
      costs were higher in non-survivors, compared to survivors (3,664 Euro vs. 1,430
      Euro, p = 0.0001), and in patients with positive cultures, compared to patients
      with negative cultures (3,198 Euro vs. 1,865 Euro, p = 0.0004). CONCLUSION: In
      cancer patients with severe sepsis and septic shock, multiple medications are
      prescribed which are associated with high cost.

PMID- 24104763
TI  - A randomized comparison of target-controlled propofol infusion and patient
      controlled sedation during ERCP.
AB  - BACKGROUND AND STUDY AIMS: Propofol is widely used during endoscopic retrograde
      cholangiopancreatography (ERCP) but high doses are recognized as a risk factor
      for sedation-related complications. The aim of this study was to compare target
      controlled infusion (TCI) with patient self-administration (patient-controlled
      sedation, PCS) of propofol during ERCP. Propofol consumption, the ease of ERCP
      performance, and speed of recovery were recorded. PATIENTS AND METHODS: A total
      of 82 patients undergoing elective ERCP were randomized 1:1 to receive propofol
      10 mg/mL using TCI (initial targeted effect-site concentration 2 MUg/mL) or PCS
      (single bolus 1 mL, lockout time set at zero). Alfentanil was administered if
      signs of insufficient analgesia occurred. Consumption of propofol and alfentanil
      was recorded, sedation levels and vital signs were monitored, the ease of ERCP
      performance, speed of recovery, and satisfaction with sedation were evaluated.
      RESULTS: All procedures were performed without interruptions or major sedation
      related complications. The mean (+/- SD) consumption of propofol was 306 +/- 124
      mg in the TCI group and 224 +/- 101 mg in the PCS group (P = 0.002). Patients in
      the PCS group recovered faster (P = 0.035). The mean (+/- SD) consumption of
      alfentanil was 0.5 +/- 0.4 mg in both groups. The combination of propofol and
      alfentanil was associated with an increased risk of sedation-related adverse
      events (P = 0.031). CONCLUSIONS: No benefits of TCI over PCS could be
      demonstrated in this study. We recommend considering PCS as a feasible option for
      propofol administration during ERCP because of its ease of use, high success
      rate, reduced consumption of propofol, and faster recovery.

PMID- 24104767
TI  - Understanding and reducing serious maternal morbidity: a step in the right
      direction.

PMID- 24104765
TI  - Cilioplasm is a cellular compartment for calcium signaling in response to
      mechanical and chemical stimuli.
AB  - Primary cilia with a diameter of ~200 nm have been implicated in development and
      disease. Calcium signaling within a primary cilium has never been directly
      visualized and has therefore remained a speculation. Fluid-shear stress and
      dopamine receptor type-5 (DR5) agonist are among the few stimuli that require
      cilia for intracellular calcium signal transduction. However, it is not known if
      these stimuli initiate calcium signaling within the cilium or if the calcium
      signal originates in the cytoplasm. Using an integrated single-cell imaging
      technique, we demonstrate for the first time that calcium signaling triggered by
      fluid-shear stress initiates in the primary cilium and can be distinguished from
      the subsequent cytosolic calcium response through the ryanodine receptor.
      Importantly, this flow-induced calcium signaling depends on the ciliary
      polycystin-2 calcium channel. While DR5-specific agonist induces calcium
      signaling mainly in the cilioplasm via ciliary CaV1.2, thrombin specifically
      induces cytosolic calcium signaling through the IP3 receptor. Furthermore, a non
      specific calcium ionophore triggers both ciliary and cytosolic calcium responses.
      We suggest that cilia not only act as sensory organelles but also function as
      calcium signaling compartments. Cilium-dependent signaling can spread to the
      cytoplasm or be contained within the cilioplasm. Our study thus provides the
      first model to understand signaling within the cilioplasm of a living cell. 

PMID- 24104768
TI  - Maintaining quality, improving access: looking beyond the individual to the team.

PMID- 24104769
TI  - Clear and proper light for obstetric research reporting.

PMID- 24104770
TI  - Credentialing based on surgical volume, physician workforce challenges, and
      patient access.
AB  - Advances within the medical profession have resulted in an increase in available
      medical therapeutic options and minimally invasive surgical techniques for common
      gynecologic conditions. In many circumstances, this has led to a reduction in
      surgical volume for many common conditions in benign gynecology. There is also
      some evidence that a threshold number of cases may exist, below which surgical
      competence may be affected. Although the practice of medicine continues to
      evolve, there is broad recognition of a projected workforce shortage of
      physicians. If credentialing or privileging bodies establish criteria based
      solely on the number of procedures performed by an individual physician, patient
      access may be greatly affected. From a public health perspective, these issues
      cannot be considered in isolation. Thoughtful analysis of existing data and
      recognition of patient access issues should be carefully weighed before any
      dramatic changes in hospital privileging or hiring practices. Consideration for
      ongoing maintenance of credentialing should be carefully balanced and strategies
      for ongoing assurance of competency may require creative alternatives to simple
      numerical documentation. Differential approaches to regions with different
      densities of physicians may also be necessary. 

PMID- 24104771
TI  - Development of a comorbidity index for use in obstetric patients.
AB  - OBJECTIVE: To develop and validate a maternal comorbidity index to predict severe
      maternal morbidity, defined as the occurrence of acute maternal end-organ injury,
      or mortality. METHODS: Data were derived from the Medicaid Analytic eXtract for
      the years 2000-2007. The primary outcome was defined as the occurrence of
      maternal end-organ injury or death during the delivery hospitalization through 30
      days postpartum. The data set was randomly divided into a two-thirds development
      cohort and a one-third validation cohort. Using the development cohort, a
      logistic regression model predicting the primary outcome was created using a
      stepwise selection algorithm that included 24-candidate comorbid conditions and
      maternal age. Each of the conditions included in the final model was assigned a
      weight based on its beta coefficient, and these were used to calculate a maternal
      comorbidity index. RESULTS: The cohort included 854,823 completed pregnancies, of
      which 9,901 (1.2%) were complicated by the primary study outcome. The derived
      score included 20 maternal conditions and maternal age. For each point increase
      in the score, the odds ratio for the primary outcome was 1.37 (95% confidence
      interval [CI] 1.35-1.39). The c-statistic for this model was 0.657 (95% CI 0.647
      0.666). The derived score performed significantly better than available
      comorbidity indices in predicting maternal morbidity and mortality. CONCLUSION:
      This new maternal comorbidity index provides a simple measure for summarizing the
      burden of maternal illness for use in the conduct of epidemiologic, health
      services, and comparative effectiveness research. LEVEL OF EVIDENCE: II.

PMID- 24104772
TI  - Increased pressure pain sensitivity in women with chronic pelvic pain.
AB  - OBJECTIVE: To determine whether women with chronic pelvic pain and variable
      degrees of endometriosis demonstrate altered pain sensitivity relative to pain
      free healthy women in a control group and whether such differences are related to
      the presence or severity of endometriosis or comorbid pain syndromes. METHODS:
      Four patient subgroups (endometriosis with chronic pelvic pain [n=42],
      endometriosis with dysmenorrhea [n=15], pain-free endometriosis [n=35], and
      chronic pelvic pain without endometriosis [n=22]) were each compared with 30
      healthy women in a control group in this cross-sectional study. All patients
      completed validated questionnaires regarding pain symptoms and underwent
      screening for comorbid pain disorders. Pain sensitivity was assessed by applying
      discrete pressure stimuli to the thumbnail using a previously validated protocol.
      RESULTS: While adjusting for age and education, pain thresholds were lower in all
      subgroups of women with pelvic pain relative to healthy women in the control
      group (all P values <.01). There was no difference in pain thresholds when
      comparing patients with endometriosis without pelvic pain with healthy women in
      the control group (mean difference 0.02 kg/m2, 95% confidence interval -0.43 to
      0.47). The presence and severity of endometriosis and number of comorbid pain
      syndromes were not associated with a difference in pain thresholds. CONCLUSION:
      Women with chronic pelvic pain demonstrate increased pain sensitivity at a
      nonpelvic site compared with healthy women in a control group, which is
      independent of the presence or severity of endometriosis or comorbid pain
      syndromes. These findings support the notion that central pain amplification may
      play a role in the development of pelvic pain and may explain why some women with
      pelvic pain do not respond to therapies aimed at eliminating endometriosis
      lesions. LEVEL OF EVIDENCE: II.

PMID- 24104773
TI  - Age as a predictor of osteoporotic fracture compared with current risk-prediction
      models.
AB  - OBJECTIVE: To compare several fracture risk-prediction models and their
      predictive values. METHODS: Women older than age 49 years were sent for dual
      energy X-ray absorptiometry screening between January 2007 and March 2009. Data
      collection included multiple osteoporosis risk factors. The ability to identify
      fractures was analyzed and compared using the North American Menopause Society
      2006 and 2010 Position Statements, The Fracture Risk Assessment Tool, along with
      age alone. The area under the curve (AUC) comparison with chance (AUC 0.50) and
      paired AUC comparisons between models were used to investigate the efficacy of
      each model in predicting osteoporotic fractures. RESULTS: Among the 615 women
      studied, with mean (standard deviation) age of 61.4 (8.3) years and 94.5% being
      white, 15 have experienced a fracture. All screening approaches were
      significantly better than chance at predicting fractures. Paired comparisons of
      the detection ability of fracture prediction models showed no significant
      differences. Age alone was a significant predictor for fracture (AUC 0.79, 95%
      confidence interval [CI] 0.67-0.91, P<.001) with the optimal cutoff age of 65
      years, which was associated with a sensitivity (95% CI) of 80% (77-83%) and
      specificity (95% CI) of 73% (70-77%). Compared with young postmenopausal women
      (younger than 65 years), the odds ratio (95% CI) of fractures in older women (65
      years or older) is 10.2 (2.32-44.97). In addition, when age was added, it
      significantly increased the AUC of each model. CONCLUSION: These data suggest
      that all current screening modalities are effective in predicting fracture but
      not significantly better than age alone. Age should be considered carefully while
      evaluating patients for osteoporosis screening and treatment. LEVEL OF EVIDENCE:
      II.

PMID- 24104774
TI  - Prevalence of symptomatic pelvic floor disorders among gynecologic oncology
      patients.
AB  - OBJECTIVE: To describe the prevalence of urinary incontinence and pelvic organ
      prolapse (POP) in patients with gynecologic cancer before cancer treatment.
      METHODS: A screening questionnaire on pelvic floor dysfunction was administered
      as part of the baseline health questionnaire to 549 consecutive new patients
      presenting to a gynecologic oncology practice. Patients were asked whether they
      felt a bulge from their vagina or experienced loss of urine associated with
      activity or urge to urinate. The prevalence of urinary incontinence, POP, or both
      was determined for each malignancy and benign conditions. chi2 analyses and
      logistic regression were used to assess significance of differences. RESULTS:
      Among the 347 women with a gynecologic malignancy, 49.9% women had uterine, 21.0%
      ovarian, and 14.4% cervical cancer. More than half of the patients with cancer
      reported baseline urinary incontinence (UI) and 10.9% felt a bulge from their
      vagina. Approximately 19% of these women had moderate-to-severe symptoms. The
      prevalence of baseline UI (P=.86) and POP (P=.08) did not differ by gynecologic
      cancer nor did they differ compared with women with benign gynecologic conditions
      (UI P=.89, POP P=.20). Logistic regression demonstrated an association between
      incontinence symptoms and increased age and body mass index (BMI). CONCLUSIONS:
      Women with gynecologic cancer show high prevalence of symptomatic POP and UI. Age
      and BMI are risk factors for UI. Coordinated surgical intervention to address
      both the malignancy and pelvic floor dysfunction could be considered in select
      patients to enhance postoperative quality of life and to reduce the economic and
      quality-of-life costs of multiple surgeries. LEVEL OF EVIDENCE: II.

PMID- 24104775
TI  - Long-term patient satisfaction with michigan four-wall sacrospinous ligament
      suspension for prolapse.
AB  - OBJECTIVE: To describe patient satisfaction after Michigan four-wall sacrospinous
      ligament suspension for prolapse and identify factors associated with
      satisfaction. METHODS: Four hundred fifty-three patients were asked to rate their
      satisfaction with surgery and complete validated quality-of-life instruments.
      Postoperative support was extracted from the medical record and assessed when
      possible. Factors independently associated with patients who were "highly
      satisfied" were identified with multivariable logistic regression. RESULTS: Sixty
      two percent (242/392) reported how satisfied they were 8.0+/-1.7 years later.
      Fifty-seven percent had failed prior prolapse surgery, and 56% had a preoperative
      prolapse 4 cm or greater beyond the hymen. Ninety percent were satisfied; 76%
      were "completely" or "very" satisfied and they were considered "highly satisfied"
      for analysis. Fourteen percent reporting being "moderately" satisfied and they
      were considered among those "less satisfied." Women with lower scores on the
      postoperative Pelvic Floor Distress Inventory-20 were more likely to be "highly
      satisfied." Postoperative anatomic data were available for 67% (162/242) and
      vaginal support was observed at or above the hymen in 86%. Women with
      preoperative Baden Walker grade 3 or 4 prolapse were more likely than those with
      grade 2 prolapse to be "highly satisfied." Women with advanced postoperative
      prolapse (grade 3 or 4) were less likely and those with grade 2 support were as
      likely to be "highly satisfied" as those with grade 0 or 1 support. CONCLUSION:
      The Michigan four-wall sacrospinous ligament suspension is an anatomically
      effective approach to vault suspension with a high rate of long-term patient
      satisfaction. Postoperative vaginal support at the hymen does not negatively
      affect patient satisfaction. LEVEL OF EVIDENCE: III.

PMID- 24104776
TI  - Childbirth and female sexual function later in life.
AB  - OBJECTIVE: To examine relationships among parity, mode of delivery, and other
      parturition-related factors with women's sexual function later in life. METHODS:
      Self-administered questionnaires examined sexual desire, activity, satisfaction,
      and problems in a multiethnic cohort of women aged 40 years and older with at
      least one past childbirth event. Trained abstractors obtained information on
      parity, mode of delivery, and other parturition-related factors from archived
      records. Multivariable regression models examined associations with sexual
      function controlling for age, race or ethnicity, partner status, diabetes, and
      general health. RESULTS: Among 1,094 participants, mean (standard deviation) age
      was 56.3 (+/-8.7) years, 568 (43%) were racial or ethnic minorities (214 African
      American, 171 Asian, and 183 Latina), and 963 (88%) were multiparous. Fifty-six
      percent (n=601) reported low sexual desire; 53% (n=577) reported less than
      monthly sexual activity, and 43% (n=399) reported low overall sexual
      satisfaction. Greater parity was not associated with increased risk of reporting
      low sexual desire (adjusted odds ratio [OR] 1.08, confidence interval [CI] 0.96
      1.21 per each birth), less than monthly sexual activity (adjusted OR 1.05, CI
      0.93-1.20 per each birth), or low sexual satisfaction (adjusted OR 0.96, CI 0.85
      1.09 per each birth). Compared with vaginal delivery alone, women with a history
      of cesarean delivery were not significantly more likely to report low desire
      (adjusted OR 0.71, CI 0.34-1.47), less than monthly sexual activity (adjusted OR
      1.03, CI 0.46-2.32), or low sexual satisfaction (adjusted OR 0.57, CI 0.26-1.22).
      Women with a history of operative-assisted delivery were more likely to report
      low desire (adjusted OR 1.38, CI 1.04-1.83). CONCLUSIONS: Among women with at
      least one childbirth event, parity and mode of delivery are not major
      determinants of sexual desire, activity, or satisfaction later in life. LEVEL OF
      EVIDENCE: II.

PMID- 24104777
TI  - Interpregnancy weight change and risk for adverse perinatal outcome.
AB  - OBJECTIVE: To examine the association between interpregnancy weight change and
      the risk for adverse maternal and neonatal outcomes. METHODS: All live-born
      singleton births delivered at 21-42 weeks of gestation in women who had their
      first two consecutive births between 2009 and 2011 in Flanders (the northern part
      of Belgium) and who were included in the Study Center for Perinatal Epidemiology
      database (N=7,897) were included. Interpregnancy weight change was calculated as
      the difference between the prepregnancy body mass index (BMI) of the first
      pregnancy and the prepregnancy BMI of the second pregnancy. Multivariate logistic
      regression analysis to predict gestational diabetes mellitus, pregnancy-induced
      hypertension, cesarean delivery, macrosomia (4,000 g or greater), low birth
      weight (less than 2,500 g), and congenital malformations were performed. RESULTS:
      The adjusted odds ratio (OR) for gestational diabetes mellitus was 2.25 (95%
      confidence interval [CI] 1.33-3.78; P=.002) for interpregnancy weight retention
      of 2 or more BMI units, and the adjusted OR for pregnancy-induced hypertension
      was 3.76 (95% CI 2.16-6.57; P<.001) with an increase of 3 or more BMI units
      between pregnancies, but these associations were only present in underweight and
      normal-weight women. In overweight and obese women, the adjusted OR was 2.04 (95%
      CI 1.41-2.95; P<.001) for cesarean delivery for an interpregnancy weight
      retention of 2 or more BMI units. In underweight and normal-weight women, the
      risk for macrosomia was halved if women lost more than 1 BMI unit between
      pregnancies, but at the same time, the risk for low birth weight doubled.
      CONCLUSION: We show that weight retention between the first and second pregnancy
      is associated with an increased risk for perinatal complications, even in
      underweight and normal-weight women. Stabilizing interpregnancy weight appears an
      important target for reducing adverse perinatal outcomes in a second pregnancy.
      LEVEL OF EVIDENCE: II.

PMID- 24104778
TI  - Outcomes of vaginal prolapse surgery among female Medicare beneficiaries: the
      role of apical support.
AB  - OBJECTIVE: Recurrent pelvic organ prolapse (POP) has been attributed to many
      factors, one of which is lack of vaginal apical support. To assess the role of
      vaginal apical support and POP, we analyzed a national dataset to compare long
      term reoperation rates after prolapse surgery performed with and without apical
      support. METHODS: Public use file data on a 5% random national sample of female
      Medicare beneficiaries were obtained from the Centers for Medicare and Medicaid
      Services. Women with POP who underwent surgery during 1999 were identified by
      relevant International Classification of Diseases, 9th Revision, Clinical
      Modification, and Current Procedural Terminology, Fourth Edition codes.
      Individual patients were followed-up through 2009. Prolapse repair was
      categorized as anterior, posterior, or anterior-posterior with or without a
      concomitant apical suspension procedure. The primary outcome was the rate of
      retreatment for POP. RESULTS: In 1999, 21,245 women had a diagnosis of POP. Of
      these, 3,244 (15.3%) underwent prolapse surgery that year. There were 2,756 women
      who underwent an anterior colporrhaphy, posterior colporrhaphy, or both with or
      without apical suspension. After 10 years, cumulative reoperation rates were
      highest among women who had an isolated anterior repair (20.2%) and significantly
      exceeded reoperation rates among women who had a concomitant apical support
      procedure (11.6%; P<.01). CONCLUSION: Ten years after surgery for POP, the
      reoperation rate was significantly reduced when a concomitant apical suspension
      procedure was performed. This analysis of a national cohort suggests that the
      appropriate use of a vaginal apical support procedure at the time of surgical
      treatment of POP might reduce the long-term risk of prolapse recurrence. LEVEL OF
      EVIDENCE: II.

PMID- 24104779
TI  - Terminal fetal heart decelerations and neonatal outcomes.
AB  - OBJECTIVE: To describe the incidence and characteristics of terminal fetal heart
      rate decelerations and to estimate their association with acidemia. METHODS: A 5
      year retrospective cohort study of all women with singleton, nonanomalous
      gestations who labored and reached complete dilation at or after 37 weeks of
      gestation. The 30 minutes of electronic fetal monitoring before delivery were
      interpreted by two formally trained research nurses, blind to clinical data,
      using American College of Obstetricians and Gynecologists guidelines. Terminal
      decelerations (decelerations without recovery of 120 seconds or more) defined the
      exposure. Terminal bradycardia (10 minutes or more) was secondarily explored.
      Univariable and multivariable analyses were performed to estimate risk of
      acidemia (umbilical cord gas arterial pH level 7.10 or less). RESULTS: Of 5,388
      women meeting inclusion criteria, 951 (17.7%) experienced a terminal deceleration
      whereas 4,437 (82.3%) did not. The incidence of acidemia among the 951 women with
      a terminal deceleration was low (1.3%; n=12). However, acidemia (adjusted odds
      ratio [OR] 18.6; 95% confidence [CI] 5.0-68.9) and higher-level nursery admission
      (adjusted OR 5.4; 95% CI 1.9-15.3) were more likely if the terminal deceleration
      was 10 minutes or more. Terminal decelerations were longer among neonates with
      acidemia (6.7 minutes compared with 3.2 minutes; P<.01). For every additional 120
      seconds of duration beyond the first 120 seconds, there was a corresponding
      decrease in umbilical cord gas pH level by 0.042 (95% CI 0.040-0.048; P<.01).
      CONCLUSIONS: More than 98% of term fetuses with terminal decelerations deliver
      with normal umbilical cord gas pH levels. However, bradycardia is associated with
      increased risk of acidemia and higher-level nursery admission. This information
      can be incorporated into clinical decision-making regarding urgency of delivery.
      LEVEL OF EVIDENCE: II.

PMID- 24104780
TI  - Association between vaginal birth after cesarean delivery and primary cesarean
      delivery rates.
AB  - OBJECTIVE: To estimate the association between vaginal birth after cesarean
      delivery (VBAC) rates and primary cesarean delivery rates in California
      hospitals. METHODS: Hospital VBAC rates were calculated using birth certificate
      and discharge data from 2009, and hospitals were categorized by quartile of VBAC
      rate. Multivariable logistic regression analysis was performed to estimate the
      odds of cesarean delivery among low-risk nulliparous women with singleton
      pregnancies at term in vertex presentation (nulliparous term singleton vertex) by
      hospital VBAC quartile while controlling for many patient-level and hospital
      level confounders. RESULTS: There were 468,789 term singleton births in
      California in 2009 at 255 hospitals, 125,471 of which were low-risk nulliparous
      term singleton vertex. Vaginal birth after cesarean delivery rates varied between
      hospitals, with a range of 0-44.6%. Rates of cesarean delivery among low-risk
      nulliparous term singleton vertex women declined significantly with increasing
      VBAC rate. When adjusted for maternal and hospital characteristics, low-risk
      nulliparous term singleton vertex women who gave birth in hospitals in the
      highest VBAC quartile had an odds ratio of 0.55 (95% confidence interval 0.46
      0.66) of cesarean delivery compared with women at hospitals with the lowest VBAC
      rates. Each percentage point increase in a hospital's VBAC rate was associated
      with a 0.65% decrease in the low-risk nulliparous term singleton vertex cesarean
      delivery rate. CONCLUSION: Hospitals with higher rates of VBAC have lower rates
      of primary cesarean delivery among low-risk nulliparous women with singleton
      pregnancies at term in vertex presentation. LEVEL OF EVIDENCE: II.

PMID- 24104781
TI  - Twenty-four-month continuation of reversible contraception.
AB  - OBJECTIVE: To estimate 24-month continuation rates of all reversible
      contraceptive methods for women enrolled in the Contraceptive CHOICE Project.
      METHODS: We analyzed 24-month data from the 9,256 participants enrolled in the
      Contraceptive CHOICE Project, a prospective observational cohort study that
      provides no-cost contraception to women in the St. Louis region. The project
      promoted the use of long-acting reversible contraception (LARC) (intrauterine
      devices [IUDs] and implants) in an effort to reduce the rates of unintended
      pregnancy. This analysis includes participants who received their baseline
      contraceptive method within 3 months of enrollment and who completed a 24-month
      follow-up survey (N=6,153). RESULTS: Twenty-four month continuation rates for
      long-acting reversible contraception and non-LARC methods were 77% and 41%,
      respectively. Continuation rates for the levonorgestrel and the copper IUDs were
      similar (79% compared with 77%), whereas the implant continuation rate was
      significantly lower (69%, P<.001) compared with IUDs at 24 months. There was no
      statistically significant difference in 24-month continuation rates among the
      four non-LARC methods (oral contraceptive pill [OCP] 43%, patch 40%, ring 41%,
      depot medroxyprogesterone acetate [DMPA] 38%; P=.72). Participants who chose a
      LARC method at enrollment were at significantly lower risk of contraceptive
      method discontinuation (adjusted hazard ratio 0.29, 95% confidence interval 0.26
      0.32) compared with women who selected a non-LARC method. CONCLUSION:
      Intrauterine devices and the implant have the highest rates of continuation at 24
      months. Given their effectiveness and high continuation rates, IUDs and implants
      should be first-line contraceptive options and shorter-acting methods such as
      OCPs, patch, ring, and DMPA should be second tier. LEVEL OF EVIDENCE: II.

PMID- 24104782
TI  - Racial disparities in the treatment of advanced epithelial ovarian cancer.
AB  - OBJECTIVE: To examine whether treatment with guideline-recommended care (surgery
      and chemotherapy) is associated with mortality differences between black and
      white women with advanced epithelial ovarian cancer. METHODS: We conducted an
      observational cohort study using the Surveillance, Epidemiology, and End Results
      (SEER) linked to Medicare claims for 1995-2007. We evaluated long-term survival
      for 4,695 black and white women with stage III or stage IV epithelial ovarian
      cancer with Kaplan-Meier analysis and Cox regression, and then in patients
      matched by propensity score to create two similar cohorts for comparison. We
      investigated the association between race, stage, and survival among women who
      were treated with guideline-recommended care and those who received incomplete
      treatment. RESULTS: Black women with advanced epithelial ovarian cancer were more
      likely to die than white women (unadjusted hazard ratio [HR] 1.27; 95% confidence
      interval [CI] 1.10-1.46). Black women were less likely than white women to
      receive guideline-recommended care (54% compared with 68%; P<.001), and women who
      did not receive recommended treatment had lower survival rates than women who
      received recommended care. Cox proportional hazards models demonstrated no
      differences in black women compared with white women regarding mortality among
      women who were treated with guideline-recommended care (adjusted HR 1.04; 95% CI
      0.85-1.26), or among women who received incomplete treatment (adjusted HR 1.09;
      95% CI 0.89-1.34). The survival analysis of patients matched by propensity score
      confirmed these analyses. CONCLUSIONS: Differences in rates of treatment with
      guideline-recommended care are associated with black-white mortality disparities
      among women with advanced epithelial ovarian cancer. LEVEL OF EVIDENCE: III.

PMID- 24104783
TI  - Cerebral autoregulation in normal pregnancy and preeclampsia.
AB  - OBJECTIVE: To test the hypothesis that preeclampsia is associated with impaired
      dynamic cerebral autoregulation. METHODS: In a prospective cohort analysis,
      cerebral blood flow velocity of the middle cerebral artery (determined by
      transcranial Doppler), blood pressure (determined by noninvasive arterial volume
      clamping), and end-tidal carbon dioxide were simultaneously collected during a 7
      minute period of rest. The autoregulation index was calculated. Values of 0 and 9
      indicated absent and perfect autoregulation, respectively. Student t test was
      used, with P<.05 considered significant. RESULTS: Women with preeclampsia (before
      treatment, n=20) and their normotensive counterparts (n=20) did not differ with
      respect to baseline characteristics, except for earlier gestational age at
      delivery (36 3/7 [24 4/7-40 2/7] compared with 39 2/7 [32 0/7-41 0/7]; P<.001)
      and higher blood pressure in women with preeclampsia. Autoregulation index was
      significantly reduced in preeclamptic women compared with normotensive women in
      the control group (5.5+/-1.7 compared with 6.7+/-0.6; P=.004). There was no
      correlation between the autoregulation index and blood pressure. CONCLUSION:
      Women with preeclampsia have impaired dynamic cerebral autoregulation. The fact
      that blood pressure does not correlate with autoregulation functionality may
      explain why cerebral complications such as eclampsia can occur without sudden or
      excessive elevation in blood pressure. LEVEL OF EVIDENCE: II.

PMID- 24104784
TI  - Disclosing a diagnosis of cancer: considerations specific to gynecologic oncology
      patients.
AB  - OBJECTIVE: To characterize gynecologic oncology patients' perceptions of the
      process of disclosure of a cancer diagnosis. METHODS: We surveyed 100 gynecologic
      oncology patients between December 2011 and September 2012. An 83-item tool based
      on three validated assessment tools evaluated patient-centered factors, physician
      behavior and communication skills, and environmental factors. Associations
      between patients' satisfaction and these variables were analyzed using Wilcoxon
      rank-sum, Kruskal-Wallis, and Spearman's rho tests. Poisson regression was used
      to assess factors associated with patient's satisfaction. RESULTS: Twenty-four
      percent of patients were notified of their diagnosis by phone, 60% in the
      physician's office, and 16% in the hospital. Disclosure was performed by an
      obstetrician-gynecologist (58%), gynecologic oncologist (26%), primary care
      physician (8%), or other (8%). Fifty-two percent of all patients were accompanied
      by a support person. Higher patient satisfaction scores were associated with face
      to-face disclosure (mean score 91% compared with over the phone 72%, P=.02), a
      private setting (mean score 92% compared with impersonal setting 72%, P=.004),
      and duration of the encounter of greater than 10 minutes (mean score 94% compared
      with less than 10 minutes 79%, P<.001). Multivariate analysis confirmed that both
      physician communication skills (P<.001) and patient-centered factors (eg,
      perception of physician sensitivity and empathy, opportunities to ask questions
      and express emotion, and set the pace of conversation; P=.013) were associated
      with higher patient satisfaction. CONCLUSIONS: Effective physician communication
      skills and patient-centered factors resulted in higher patient satisfaction with
      the gynecologic cancer diagnosis disclosure experience. LEVEL OF EVIDENCE: II.

PMID- 24104785
TI  - Scope of global health training in U.S. obstetrics and gynecology residency
      programs.
AB  - OBJECTIVE: To enumerate global health training activities in U.S. obstetrics and
      gynecology residency programs and to examine the worldwide distribution of
      programmatic activity relative to the maternal and perinatal disease burden.
      METHODS: Using a systematic, web-based protocol, we searched for global health
      training opportunities at all U.S. obstetrics and gynecology residency programs.
      Country-level data on disability-adjusted life-years resulting from maternal and
      perinatal conditions were obtained from the Global Burden of Disease study. We
      calculated Spearman's rank correlation coefficients to estimate the cross-country
      association between programmatic activity and disease burden. RESULTS: Of the 243
      accredited U.S. obstetrics and gynecology residency programs, we identified 41
      (17%) with one of several possible predefined categories of programmatic
      activity. Thirty-three residency programs offered their residents opportunities
      to participate in one or more elective-based rotations, eight offered extended
      field-based training, and 18 offered research activities. A total of 128
      programmatic activities were dispersed across 64 different countries. At the
      country level, the number of programmatic activities had a statistically
      significant association with the total disease burden resulting from maternal
      (Spearman's rho=0.37, 95% confidence interval [CI] 0.14-0.57) and perinatal
      conditions (rho=0.34, 95% CI 0.10-0.54) but not gynecologic cancers (rho=-0.24,
      95% CI -0.46 to 0.01). CONCLUSIONS: There are few global health training
      opportunities for U.S. obstetrics and gynecology residents. These activities are
      disproportionately distributed among countries with greater burdens of disease.
      LEVEL OF EVIDENCE: II.

PMID- 24104786
TI  - Challenges in academic obstetrics and gynecology departments.
AB  - OBJECTIVE: In 2011, the Association of American Medical Colleges conducted a
      multicenter survey to assess faculty satisfaction, engagement, and retention.
      This subanalysis describes the perceptions of academic obstetrician-gynecologists
      (ob-gyns). METHOD: Fourteen U.S. institutions offered voluntary faculty survey
      participation. We analyzed demographic information and responses to items within
      the 10 work-related dimensions. This analysis used pooled cohort data for 329 ob
      gyn respondents across institutions. RESULTS: The mean response rate was 61.7%
      (9,600/15,570) overall and 66.9% for ob-gyn respondents. Most ob-gyn respondents
      reported satisfaction with work-related autonomy (72.2%) and a sense of
      accomplishment in their day-to-day activities (81.9%), including clarity about
      how their day-to-day activities fit into their medical school's mission (68.4%).
      In an average week, ob-gyn respondents reported working 59.4 hours on average.
      The mean percentage of effort varied by activity: patient care (54.8%), teaching
      (18.1%), research and scholarship (17.0%), and administration (15%). The mean
      proportion of ob-gyn respondents reporting that far too much or too much of their
      time and effort was spent on patient care was 35.1%, with more than half (59.5%)
      reporting far too little or too little of their time and effort was spent on
      research and scholarship and a third (33.3%) reporting far too little or too
      little time and effort devoted to teaching. Although 60.9% of respondents thought
      a mentor at their institution was important, only 22.2% reported a formal
      mentoring relationship. In the next 1-2 years, 13.4% reported seriously planning
      or being undecided (18.8%) about leaving their medical school. CONCLUSION:
      Academic obstetrics and gynecology departments face challenges balancing faculty
      members' academic desires and clinical demands. LEVEL OF EVIDENCE: II.

PMID- 24104788
TI  - A suggested approach for implementing CONSORT guidelines specific to obstetric
      research.
AB  - The conduct and reporting of randomized controlled trials (RCTs) are enhanced by
      being compliant with the CONsolidated Standards of Reporting Trials (CONSORT)
      statement. The statement was meant to be general and was aimed at most RCTs
      without any particular focus on specific groups of patients. However, research in
      pregnancy presents important unique issues and challenges that are not addressed
      in the CONSORT statement. Thus, we suggest that there is a need to amend the
      statement to address RCTs enrolling pregnant or postpartum women. We propose
      CONSORT-OB (OBstetrics), with more than 30 modifications to the current
      statement. We hope the CONSORT group would consider our proposal, and we
      respectfully suggest that investigators incorporate these additional data into
      their reporting of RCTs involving pregnant or postpartum women. 

PMID- 24104789
TI  - Exclusion of pregnant women from industry-sponsored clinical trials.
AB  - OBJECTIVE: The lack of human data available to inform evidence-based treatment
      for illness during pregnancy has led to calls for greater inclusion of pregnant
      women in research, but the extent of their current representation is poorly
      characterized. Our objective was to measure the current exclusion of pregnant
      women from industry-sponsored clinical trials as a baseline for future
      comparison. METHODS: We compiled data from studies enrolling women of
      childbearing potential posted on www.ClinicalTrials.gov between 1 October 2011
      and 31 January 2012. The review was limited to open United States-based phase IV
      interventional studies sponsored by the pharmaceutical industry evaluating
      treatment of conditions that may be experienced by but are not limited to
      pregnant women and did not involve a medication classified as potentially
      teratogenic. If there was no mention of pregnancy in the inclusion or exclusion
      criteria, we contacted a study representative to confirm that pregnant women
      could be enrolled. RESULTS: Of 558 qualifying industry-sponsored studies, five
      (1%) were designed specifically for pregnant women. Of 367 phase IV clinical
      trials with verified inclusion and exclusion criteria, 348 (95%) excluded
      pregnant women and 19 (5%) did not. CONCLUSION: We found the exclusion of
      pregnant women from industry-sponsored clinical trials to be common practice.
      Moving beyond reflexive exclusion and developing thoughtful criteria for
      inclusion of pregnant women in clinical research would likely advance the
      evidence base to inform treatment decisions during pregnancy and lead to better
      health outcomes for women and children.

PMID- 24104787
TI  - Contemporary labor patterns and maternal age.
AB  - OBJECTIVE: To evaluate labor progress and length according to maternal age.
      METHODS: Data were abstracted from the Consortium on Safe Labor, a multicenter
      retrospective study from 19 hospitals in the U.S. We studied 120,442 laboring
      gravid women with singleton, term, cephalic fetuses with normal outcomes and
      without a prior cesarean delivery from 2002 to 2008. Maternal age categories were
      younger than 20 years of age, 20-29 years of age, 30-39 years of age, and 40
      years of age or older with the reference being younger than 20 years of age.
      Interval-censored regression analysis was used to determine median traverse times
      (progression centimeter by centimeter) with 95th percentiles adjusting for
      covariates (race, admission body mass index, diabetes, gestational age,
      induction, augmentation, epidural use, and birth weight). A repeated-measures
      analysis with an eighth-degree polynomial model was used to construct mean labor
      curves for each maternal age category stratified by parity. RESULTS: Traverse
      times for nulliparous women demonstrated the time to progress from 4 to 10 cm
      decreased as age increased up to age 40 years (median 8.5 hours compared with 7.8
      hours in those 20-29 years of age group and 7.4 hours in the 30-39 years of age
      group, P<.001); the length of the second stage with and without epidural
      increased with age (P<.001). For multiparous women, time to progress from 4 to 10
      cm decreased as age increased (median 8.8 hours, 7.5, 6.7, and 6.5 from the
      youngest to oldest maternal age groups, P<.001). Labor progressed faster with
      increasing maternal age in both nulliparous and multiparous women in the labor
      curves analysis. CONCLUSION: The first stage of labor progressed more quickly
      with increasing age for nulliparous women up to age 40 years and all multiparous
      women. Contemporary labor management should account for maternal age. LEVEL OF
      EVIDENCE: II.

PMID- 24104790
TI  - Oral nifedipine or intravenous labetalol for hypertensive emergency in pregnancy:
      a randomized controlled trial.
AB  - OBJECTIVE: To compare the effectiveness of orally administered nifedipine and
      intravenously administered labetalol for acute blood pressure control in
      hypertensive emergency of pregnancy. METHODS: In this double-blind, randomized,
      controlled trial, pregnant women with sustained increase in systolic blood
      pressure of 160 mm Hg or higher or diastolic blood pressure of 110 mm Hg or
      higher were randomized to receive nifedipine (10 mg tablet orally up to five
      doses) and intravenous placebo saline injection or intravenous labetalol
      injection in escalating doses of 20, 40, 80, 80, and 80 mg and a placebo tablet
      every 20 minutes until the target blood pressure of 150 mm Hg systolic and 100 mm
      Hg diastolic, or lower, was achieved. Crossover treatment was administered if the
      initial treatment failed. The primary endpoint of the study was time necessary to
      achieve target blood pressure. Secondary endpoints were number of dosages
      required, adverse maternal and neonatal effects, side effect profile, and
      perinatal outcome. RESULTS: From October 2012 to April 2013, we enrolled 60
      patients. The median time taken to achieve target blood pressure was 40 minutes
      (interquartile range, 20-60 minutes) compared with 60 minutes (interquartile
      range 40-85 minutes) for nifedipine and labetalol, respectively (P=.008). The
      median dose required was two (interquartile range 1-3) compared with three
      (interquartile range 2-4.25) for nifedipine and labetalol, respectively (P=.008).
      No serious adverse maternal or perinatal side effects were witnessed in either
      group. CONCLUSION: As administered in this trial, oral nifedipine lowered blood
      pressure more quickly than did intravenous labetalol during hypertensive
      emergency in pregnancy. CLINICAL TRIAL REGISTRATION: Clinical Trials Registry
      India, www.ctri.nic.in, CTRI/2013/02/003350. LEVEL OF EVIDENCE: I.

PMID- 24104791
TI  - Terahertz surface plasmon excitation via nonlinear mixing of lasers in a metal
      coated optical fiber.
AB  - Terahertz (THz) surface plasmon generation via nonlinear mixing of laser
      eigenmodes in an optical fiber coated with ultrathin metal foil and possessing a
      dielectric constant ripple of wave number q is investigated. The fiber supports
      THz surface plasma wave (SPW) with plasmon resonance in the THz domain and is
      controllable by film thickness. The lasers exert a difference frequency
      ponderomotive force on the electrons of the metal film. The ponderomotive force
      induces a nonlinear current driving the difference frequency THz SPW. THz
      amplitude to laser amplitude ratio of the order ~10(-2) can be achieved by CO2
      laser in megawatt range.

PMID- 24104792
TI  - Route to stabilized ultrabroadband microresonator-based frequency combs.
AB  - We perform the first theoretical modeling of the full spectral-temporal dynamics
      of octave-spanning parametric microresonator comb generation through use of the
      Lugiato-Lefever model extended to include higher-order dispersion and self
      steepening. We show that three distinct stages are necessary to achieve single
      pulse modelocking and discuss the dispersion characteristics required for
      ultrabroadband, stabilized comb generation. Our simulations agree well with
      previous experimental demonstrations and predict many of the observed features,
      including multipulse generation, dispersive wave generation, modelocking, and
      comb stabilization. 

PMID- 24104793
TI  - Tolerant polarization converter for InGaAsP-InP photonic integrated circuits.
AB  - We report the fabrication and characterization of a new polarization converter
      for InGaAsP-InP photonic integrated circuits. The converter consists of two right
      trapezoidal sections with the angled sidewalls etched wetly. The converters show
      a greatly improved tolerance to variations of the fabrication, an averaged
      efficiency of polarization conversion of 99.8% and a loss of about 0.7 dB at a
      wavelength of 1.535 MUm. 

PMID- 24104794
TI  - Quantum-confined photoluminescence from Ge(1-x)Sn(x)/Ge superlattices on Ge
      buffered Si(001) substrates.
AB  - We report the first observation of room-temperature quantum-confined
      photoluminescence (PL) from low-dimensional Ge(1-x)Sn(x)/Ge superlattices (SLs)
      up to a high Sn content of 6.96%. Both direct and indirect emissions associated
      with the interband transitions between minibands in the conduction bands and
      valence band were observed at room temperature. As the Sn content is increased,
      the energy difference between the lowest direct and indirect transitions is
      reduced, indicating an effective modification of the band structure desired for
      optoelectronics. The integrated PL intensity ratio of direct to indirect
      recombinations is significantly enhanced with increasing Sn content due to the
      reduced Gamma-L energy separation and quantum confinement effect. Those results
      suggest that Sn-based low-dimensional structures are promising material for
      efficient Si-based lasers.

PMID- 24104795
TI  - BER performance of MSK in ground-to-satellite uplink optical communication under
      the influence of atmospheric turbulence and detector noise.
AB  - Minimum shift keying (MSK) has been widely used in fiber optical communication
      and free-space optical communication. In order to introduce MSK into satellite
      laser communication, the bit-error rate (BER) performance of the MSK scheme is
      investigated in uplink communications under the influence of atmospheric
      turbulence consisting of weak fluctuation and beam wander. Numerical results
      indicate that the BER performance of MSK is much better than the performance of
      on-off keying (OOK). With the laser power being 4 W, the improvement is 5 dB in
      coherent demodulation and 15 dB in delay coherent demodulation. Furthermore,
      compared with OOK, optimal values of the divergence angle, receiver diameter, and
      transmitter beam radius are easier and more practical to achieve in the MSK
      scheme. The work can benefit ground-to-satellite laser uplink communication
      system design. 

PMID- 24104796
TI  - Subwavelength plasmonics for graded-index optics on a chip.
AB  - Planar plasmonic devices are becoming attractive for myriad applications, owing
      to their potential compatibility with standard microelectronics technology and
      the capability for densely integrating a large variety of plasmonic devices on a
      chip. Mitigating the challenges of using plasmonics in on-chip configurations
      requires precise control over the properties of plasmonic modes, in particular
      their shape and size. Here we achieve this goal by demonstrating a planar
      plasmonic graded-index lens focusing surface plasmons propagating along the
      device. The plasmonic mode is manipulated by carving subwavelength features into
      a dielectric layer positioned on top of a uniform metal film, allowing the local
      effective index of the plasmonic mode to be controlled using a single binary
      lithographic step. Focusing and divergence of surface plasmons is demonstrated
      experimentally. The demonstrated approach can be used for manipulating the
      propagation of surface plasmons, e.g., for beam steering, splitting, cloaking,
      mode matching, and beam shaping applications. 

PMID- 24104797
TI  - Wavelength reuse in a bidirectional radio-over-fiber link based on cross-gain and
      cross-polarization modulation in a semiconductor optical amplifier.
AB  - Wavelength reuse in a bidirectional radio-over-fiber link is proposed and
      demonstrated based on the cross-gain modulation (XGM) and the cross-polarization
      modulation in a semiconductor optical amplifier (SOA). With a polarization beam
      splitter placed at the remote antenna unit, the polarization-modulated signal
      generated at the SOA is converted into noninverted and inverted intensity
      modulated signals. The noninverted signal is used to cancel the inverted XGM
      induced intensity-modulated signal to form a clean optical carrier for wavelength
      reuse in upstream signal transmission, while the inverted intensity-modulated
      signal is combined constructively to enhance the XGM-induced signal, providing
      robust downlink service. A bidirectional transmission of 5 GHz RF signal carrying
      a 50 MBaud 16 quadrature amplitude modulation baseband signal is experimentally
      implemented. The error vector magnitude degradation due to the fiber transmission
      for both the downlink and uplink signal is about 0.2%. 

PMID- 24104798
TI  - Broadband infrared quarter wave plate realized through perpendicular-to-helical
      axis wave propagation in a helix array.
AB  - The ability of helix arrays to filter circularly polarized light efficiently when
      the light propagates parallel to the helical axis has been demonstrated recently.
      In this Letter, we present a broadband linear-to-circular polarization
      transformer composed of metal microhelices. The device provides significant
      transformation performance combined with high transmittance over a broad infrared
      wave band. High performance is achieved through fine adjustment of a finite
      element electromagnetic model. The array design assumes wave propagation
      perpendicular to the helical axis, which distinguishes it from well-studied
      analogous designs that filter light propagating parallel to the helical axis. To
      the best of our knowledge, this is the first time this scheme has been realized
      in the infrared range. 

PMID- 24104799
TI  - 40 Gb/s dynamic wavelength-division-multiplexing/time-division-multiplexing
      hybrid access network with energy and data stream synchronized transmission.
AB  - A dynamic wavelength-division-multiplexing/time-division-multiplexing hybrid
      access network with energy and data synchronized transmission is proposed to
      support flexible resource allocation. Dynamic scheduling of wavelength with
      different split ratio nodes is realized by the control model at the optical
      distribution network (ODN). All-optical amplification of the optical data signal
      and energy supply are also incorporated in the ODN. A proof-of-concept experiment
      is implemented to verify the feasibility of the proposal. 

PMID- 24104800
TI  - Tunable, pulsed multiline intracavity optical parametric oscillator using two
      dimensional MgO: periodically poled lithium niobate-aperiodically poled lithium
      niobate.
AB  - We report a tunable, pulsed multiline intracavity optical parametric oscillator
      (IOPO) realized in an Nd:YVO4 laser using a two-dimensionally domain engineered
      MgO:LiNbO3 as simultaneously an electro-optic Bragg Q switch and a multichannel
      optical parametric downconverter. The MgO:LiNbO3 was periodically and
      aperiodically poled along the crystallographic y and x axes, respectively, to
      simultaneously satisfy the phase-matching conditions required by the two quasi
      phase-matching devices. When Q switched by 1 kHz, 300 V pulses, three signal
      lines at 1518, 1526, and 1534 nm were simultaneously generated, each with a peak
      power of ~1  kW from the IOPO at 8.3 W diode power at 50 degrees C. Spectral
      tuning of the three-line IOPO with temperature was demonstrated.

PMID- 24104801
TI  - Fermat principle based reflector design for fast and contactless freeform optical
      component inspections.
AB  - We propose a well-designed reflector, based on the Fermat principle, that is
      placed on a transmitted optical path to reflect the impinging light on the
      surface so that the null testing of the interference inspection for the freeform
      lens can be realized. The design methodology of such a reflector for a freeform
      lens with rotational symmetry is given and a reflector designed for a high-order
      aspheric surface is manufactured. Our investigations show that the theoretical
      accuracy of such an interference inspection can be up to 10(-7)  mm with the
      designed reflector. We fabricated the designed reflector by a single point
      diamond turning machine and a high-order aspheric lens was measured with our
      methods, showing a good agreement with conventional interference inspection
      approaches. This might open a way to the fast inspection of freeform surfaces and
      thus improve the efficiencies of optical testing.

PMID- 24104802
TI  - Macroscopic response in active nonlinear photonic crystals.
AB  - We derive macroscopic equations of motion for the slowly varying electric field
      amplitude in three-dimensional active nonlinear optical nanostructures. We show
      that the microscopic Maxwell equations and polarization dynamics can be
      simplified to a macroscopic one-dimensional problem in the direction of group
      velocity. For a three-level active material, we derive the steady-state equations
      for normal mode frequency, threshold pumping, nonlinear Bloch mode amplitude, and
      lasing in photonic crystals. Our analytical results accurately recapture the
      results of exact numerical methods. 

PMID- 24104803
TI  - Beam deflection measurement of time and polarization resolved ultrafast nonlinear
      refraction.
AB  - We modify the well-known photothermal beam deflection technique to study
      ultrafast nonlinearities. Using phase-sensitive detection we directly measure the
      temporal and polarization dynamics of nonlinear refraction (NLR) with sensitivity
      to optically induced phase changes of approximately lambda/20,000. We use the
      relative polarization dependence of excitation and probe to separate the
      isotropic and reorientational components of the NLR. 

PMID- 24104804
TI  - Radiative transfer theory verified by controlled laboratory experiments.
AB  - We report the results of high-accuracy controlled laboratory measurements of the
      Stokes reflection matrix for suspensions of submicrometer-sized latex particles
      in water and compare them with the results of a numerically exact computer
      solution of the vector radiative transfer equation (VRTE). The quantitative
      performance of the VRTE is monitored by increasing the volume packing density of
      the latex particles from 2% to 10%. Our results indicate that the VRTE can be
      applied safely to random particulate media with packing densities up to ~2%. VRTE
      results for packing densities of the order of 5% should be taken with caution,
      whereas the polarized bidirectional reflectivity of suspensions with larger
      packing densities cannot be accurately predicted. We demonstrate that a simple
      modification of the phase matrix entering the VRTE based on the so-called static
      structure factor can be a promising remedy that deserves further examination. 

PMID- 24104805
TI  - Multiple zone multifocal phase designs.
AB  - New multifocal phase designs aiming at expanding depth of focus in the presbyopic
      eye are presented. The designs consist of multiple radial or angular zones of
      different powers or of combined low- and high-order aberrations. Multifocal
      performance was evaluated in terms of the dioptric range for which the optical
      quality is above an appropriate threshold, as well as in terms of the area under
      the through-focus optical quality curves. For varying optical power designs
      optimal through-focus performance was found for a maximum of three to four zones.
      Furthermore adding more zones decreased the optical performance of the solution.
      Angular zone designs provided better multifocal performance (1.95 times on
      average) than radial zone designs with identical number of zones and the same
      power range. The optimal design (angular design with three zones) surpassed by
      33% the multifocal performance of a bifocal angular zone design and by 32% a
      standard multifocal phase plate with induced spherical aberration only. By using
      combinations of low- and high-order aberrations the through-focus range can be
      extended further by another 0.5 D beyond that of the best design of varying
      optical power. These designs can be implemented in adaptive optics systems for
      testing their visual performance in subjects and converted into multifocal
      contact lenses, intraocular lenses, or presbyopic corneal laser ablation
      profiles. 

PMID- 24104806
TI  - Fabrication of silicon reflection-type arrayed-waveguide gratings with
      distributed Bragg reflectors.
AB  - Silicon reflection-type arrayed-waveguide gratings (AWGs) consisting of all
      straight array waveguides are experimentally demonstrated for the first time to
      our knowledge. The AWG has 14 output channels with 400 GHz channel spacing and a
      footprint of 230  MUm*530  MUm. The minimum on-chip loss of 3.0 dB and crosstalk
      of -20  dB are achieved by using a second-order distributed Bragg reflector
      facet. 

PMID- 24104807
TI  - Trap-door optical buffering using a flat-top coupled microring filter: the
      superluminal cavity approach.
AB  - We propose and analyze theoretically a trap-door optical buffer based on a
      coupled microrings flat-top add/drop filter (ADF). By tuning one of the
      microrings into and out of resonance we can effectively open and close the buffer
      trap door and, consequently, trap and release optical pulses. To attain a
      maximally flat filter we present a new design approach utilizing the concept of a
      white light cavity to attain an ADF that resonates over a wide spectral band. We
      show that the resulting ADF exhibits superior performance in terms of bandwidth
      and flatness compared to previous design approaches. We also present a realistic
      silicon-on-insulator-based design and a performance analysis, taking into
      consideration the realistic properties and limitations of the materials and the
      fabrication process, leading to delays exceeding 5 ns for an 80 GHz bandwidth and
      a corresponding delay-bandwidth product of approximately 400. 

PMID- 24104808
TI  - Noninterferometric single-shot quantitative phase microscopy.
AB  - We present a noninterferometric single-shot quantitative phase microscopy
      technique with the use of the transport of intensity equation (TIE). The optical
      configuration is based on a Michelson-like architecture attached to a nonmodified
      inverted transmission bright field microscope. Two laterally separated images
      from different focal planes can be obtained simultaneously by a single camera
      exposure, enabling the TIE phase recovery to be performed at frame rates that are
      only camera limited. Precise measurement of a microlens array validates the
      principle and demonstrates the accuracy of the method. Investigations of chemical
      induced apoptosis and the phagocytosis process of macrophages are then presented,
      suggesting that the method developed can provide promising applications in the
      dynamic study of cellular processes. 

PMID- 24104809
TI  - N-doped ZnO thin film for development of magnetic field sensor based on surface
      plasmon resonance.
AB  - Magnetic-field-dependent optical properties of nitrogen-doped ZnO (ZnO:N) thin
      films were investigated using surface plasmon resonance (SPR) and a highly
      sensitive (4.65/Tesla) magnetic field sensor has been realized. The refractive
      index (RI) of ZnO:N film increases from 1.949 to 2.025 with increase in N doping
      from 0% to 10% demonstrating tunable RI. In contrast to pure ZnO, SPR curves for
      ZnO:N films exhibit a shift toward lower angles with increasing applied magnetic
      field from 0 to 35 mT due to change in reflectance of light upon reflection from
      ferromagnetic surface. Results indicate promising application of ferromagnetic
      ZnO:N film as a magnetic field sensor. 

PMID- 24104810
TI  - Exact solution to simultaneous intensity and phase encryption with a single phase
      only hologram.
AB  - A phase-only hologram applies a modal transformation to an optical transverse
      spatial mode via phase encoding and intensity masking. Accurate control of the
      optical field crucially depends on the method employed to encode the hologram. In
      this Letter, we present a method to encode the amplitude and the phase of an
      optical field into a phase-only hologram, which allows the exact control of
      spatial transverse modes. Any intensity masking method modulates the amplitude
      and alters the phase of the optical field. Our method consists in correcting for
      this unwanted phase alteration by modifying the phase encryption accordingly. We
      experimentally verify the accuracy of our method by applying it to the generation
      and detection of transverse spatial modes in mutually unbiased bases of dimension
      two and three. 

PMID- 24104811
TI  - Nonlinear control of absorption in one-dimensional photonic crystal with graphene
      based defect.
AB  - Perfect, narrow-band absorption is achieved in an asymmetric 1D photonic crystal
      with a monolayer graphene defect. Thanks to the large third-order nonlinearity of
      graphene and field localization in the defect layer we demonstrate the
      possibility to achieve controllable, saturable absorption for the pump frequency.

PMID- 24104812
TI  - Free-space to single-mode collection efficiency enhancement using photonic
      lanterns.
AB  - We demonstrate single-mode collection efficiency enhancement for free space
      optical systems using a photonic lantern to collect scattered infrared light from
      diffuse objects at far- and near-field distances. A single-mode collection
      efficiency improvement of ~8  dB is demonstrated in the near-field region
      relative to standard single-mode fiber. The insertion loss properties of the
      photonic lantern are also analyzed, and an additional insertion loss penalty is
      observed for near-field distances when the transmitted beam is collimated. The
      photonic lantern can be used for coherent detection systems such as light
      detection and ranging and free-space optical communication with improved
      collection efficiency and nearly perfect mode matching. 

PMID- 24104813
TI  - Femtosecond double-pulse fabrication of hierarchical nanostructures based on
      electron dynamics control for high surface-enhanced Raman scattering.
AB  - This Letter presents a simple, efficient approach for high surface-enhanced Raman
      scattering by one-step controllable fabrication of hierarchical structures
      (nanoparticles+subwavelength ripples) on silicon substrates in silver nitrate
      solutions using femtosecond double pulses based on nanoscale electron dynamics
      control. As the delays of the double pulses increase from 0 fs to 1 ps, the
      hierarchical structures can be controlled with (1) nanoparticles--the number of
      nanoparticles in the range of 40-100 nm reaches the maximum at 800 fs and (2)
      ripples--the subwavelength ripples become intermittent with decreased ablation
      depths. The redistributed nanoparticles and the modified ripple structures
      contribute to the maximum enhancement factor of 2.2*10(8) (measured by 10(-6)  M
      rhodamine 6G solution) at the pulse delay of 800 fs.

PMID- 24104814
TI  - Thermo-optical bistability with Si nanocrystals in a whispering gallery mode
      resonator.
AB  - We report on the observation of optical bistability in an integrated planar
      microresonator with embedded silicon nanocrystals (Si-ncs). The phenomenon
      originates from the thermo-optical modulation of the silica-embedded Si-ncs
      refractive index, which in turn alters the spectral position of the resonator
      mode. The estimated thermo-optical coefficient of the Si nanocrystalline
      material, dn/dT~2.92*10(-5)>  K(-1), is an order of magnitude lower than that of
      bulk silicon. Both time-resolved pump-and-probe experiments and numerical
      simulations confirm that the silica host is responsible for the heat dissipation
      from the resonator. Moreover, a negligible Q-factor degradation at pump powers as
      high as 100 mW, along with the absence of a fast component in time-resolved
      measurements, confirm the minute contribution from excited carriers effects.
      These observations, combined with the already published large third-order
      nonlinearities of Si-ncs (an order of magnitude larger than in bulk Si), make
      this system an outstanding candidate for low-power on-chip nonlinear comb
      generation.

PMID- 24104816
TI  - Effective magnetic fields for photons in waveguide and coupled resonator
      lattices.
AB  - A method to realize effective magnetic fields for photons in square lattices of
      coupled optical waveguides or resonators is suggested, which is inspired by an
      optical analogue of photon-assisted tunneling of atom optics. It is shown that an
      artificial magnetic field can be achieved by application of an index gradient and
      periodic lumped phase shifts or modulation of the propagation
      constants/resonances, without the need to modulate the coupling strength. 

PMID- 24104815
TI  - Quantitative assessment of renal arterial occlusion in a porcine model using
      spatial frequency domain imaging.
AB  - We present the results of a feasibility study with spatial frequency domain
      imaging (SFDI) to produce quantitative measurements of optical property and
      chromophore concentration maps of three porcine kidneys utilizing a renal
      occlusion model at the near-infrared wavelengths of 658, 730, and 850 nm. Using
      SFDI, we examined the dynamics of absolute oxygen saturation (StO2). The mean
      StO2 for the kidneys varied from approximately 60% before occlusion, to 20%
      during occlusion, to 55% after reperfusion. We also present, for the first time
      to the best of our knowledge, reduced scattering coefficient (MU(s)') maps of the
      kidney during occlusion. We observed a substantial decrease in the wavelength
      dependence of scattering (i.e., scattering power) in the three kidneys, with a
      mean decrease of 18%+/-2.6%, which is indicative of an increase in scatterer
      size, and is likely due to tissue changes such as edema that follow from
      occlusion and inflammation.

PMID- 24104817
TI  - Closed-loop locking of an optical frequency comb to a large ring laser.
AB  - We report on the frequency locking of a 16  m2 ring laser to a single tooth of an
      optical frequency comb referenced to a hydrogen maser, obtaining a frequency
      stability of 1 kHz over several days. In common mode operation, where the
      counterpropagating laser beams run on the same longitudinal mode index, a
      sensitivity to rotation of 3*10(-9) relative to Earth's rotation is obtained. To
      test a proposal to bypass time-varying backscatter-induced readout errors in
      large ring laser gyroscopes, we have operated the laser on adjacent longitudinal
      cavity modes. The Sagnac frequency due to Earth's rotation obtained in this
      fashion was strongly influenced by atmospheric pressure changes because the
      counterpropagating beams within the cavity are affected differently by geometric
      cavity fluctuations.

PMID- 24104818
TI  - MTF formalism for measurement of spectral resolution of acousto-optical devices
      with synthesized transmission function.
AB  - We demonstrate use of the modulation transfer function method in the spectral
      domain for dynamic measurement of the spectral resolution and modulation contrast
      of acousto-optic light dispersive delay lines and programmable filters with
      synthesized transmission. The method is useful for performance characterization
      of acousto-optic devices for ultrafast pulse shaping and adaptive spectroscopy. 

PMID- 24104819
TI  - High-speed thermoreflectance microscopy using charge-coupled device-based Fourier
      domain filtering.
AB  - We present a Fourier-domain filtering method for charge-coupled device (CCD)
      based thermoreflectance microscopy to improve the thermal imaging speed while
      maintaining high thermal sensitivity. The time-varying reflected light
      distribution from the surface of bias-modulated microresistor was recorded by a
      CCD camera in free-run mode and converted to the frequency domain using the fast
      Fourier transform (FFT) for all pixels of the CCD. After frequency peak filtering
      followed by inverse FFT, a thermoreflectance image was obtained. The imaging
      results of the proposed method were quantitatively compared with those of the
      conventional four-bucket method, showing that the Fourier-domain filtering method
      can provide thermal imaging 24-42 times faster than the four-bucket method,
      depending on the required thermal sensitivity. 

PMID- 24104820
TI  - Interactions between self-channeled optical beams in soft-matter systems with
      artificial nonlinearities.
AB  - We demonstrate optical interactions between stable self-trapped optical beams in
      soft-matter systems with pre-engineered saturable self-focusing optical
      nonlinearities. Our experiments, carried out in dilute suspensions of particles
      with negative polarizabilities, show that optical beam interactions can vary from
      attractive to repulsive, or can display an energy exchange depending on the
      initial relative phases. The corresponding observations are in good agreement
      with theoretical predictions. 

PMID- 24104821
TI  - Colorless grating couplers realized by interleaving dispersion engineered
      subwavelength structures.
AB  - We investigate the waveguide dispersion of subwavelength structures, and propose
      that the waveguide dispersion can be reduced by reducing the period of
      subwavelength structures. A 3 dB bandwidth increment of 20% has been observed by
      introducing this concept into previously demonstrated grating couplers. To fully
      exploit the bandwidth merits of the structures, gratings with interleaved
      subwavelength structures were designed and fabricated. Two typical types of
      interleaving geometries have been investigated. Both demonstrated a 1 dB
      bandwidth ~70  nm, a 3 dB bandwidth ~117  nm, and a peak efficiency ~-5.1  dB at
      1570 nm for transverse-electric polarized light. The simulation confirms that the
      dispersion engineering adds an extra 12 nm to the 1 dB bandwidth. 

PMID- 24104822
TI  - Two techniques for temporal pulse compression in gas-filled hollow-core kagome
      photonic crystal fiber.
AB  - We demonstrate temporal pulse compression in gas-filled kagome hollow-core
      photonic crystal fiber (PCF) using two different approaches: fiber-mirror
      compression based on self-phase modulation under normal dispersion, and soliton
      effect self-compression under anomalous dispersion with a decreasing pressure
      gradient. In the first, efficient compression to near-transform-limited pulses
      from 103 to 10.6 fs was achieved at output energies of 10.3 MUJ. In the second,
      compression from 24 to 6.8 fs was achieved at output energies of 6.6 MUJ, also
      with near-transform-limited pulse shapes. The results illustrate the potential of
      kagome-PCF for postprocessing the output of fiber lasers. We also show that,
      using a negative pressure gradient, ultrashort pulses can be delivered directly
      into vacuum. 

PMID- 24104823
TI  - Waveguide-enhanced 2D-IR spectroscopy in the gas phase.
AB  - A method for obtaining high-quality 2D-IR spectra of gas-phase samples is
      presented. Time-resolved IR absorption spectroscopy techniques, such as 2D-IR
      spectroscopy, often require that beams are focused into the sample. This limits
      the exploitable overlapped path length through samples to a few millimeters. To
      circumvent this limitation, 2D-IR experiments have been performed within a hollow
      waveguide. This has enabled acquisition of 2D-IR spectra of low-concentration gas
      phase samples, with more than an order of magnitude signal enhancement compared
      with the equivalent experiment in free space. The technique is demonstrated by
      application to the 2D-IR spectroscopy of iron pentacarbonyl. 

PMID- 24104824
TI  - High-sensitivity roll-angle interferometer.
AB  - A roll-angle interferometer with high sensitivity is presented in this Letter.
      Two sets of centrosymmetric beams are used to travel through the measurement and
      reference arms of the roll-angle interferometer, which contains two specific
      optical devices: wedge prism assembly and wedge mirror assembly. Changes of the
      optical path in the interferometric arms caused by roll are differential and
      converted into phase shift through a particular interferometer system. The
      interferometric beams are a completely common path for the adoption of the
      centrosymmetric measurement structure, and the cross talk of the straightness,
      yaw, and pitch errors is avoided. The dead path is minimized, so the stability
      and the accuracy of the measurement can be greatly enhanced. The experimental
      results fit well with the theoretical analysis, and a measurement resolution of
      sub-microradian is achieved experimentally. 

PMID- 24104825
TI  - Fiber-based tunable microcavity fluidic dye laser.
AB  - We investigate a tunable fluidic dye laser formed by a microcavity filled with a
      dye solution. We achieve a wide 18 nm tunability of the laser wavelength by
      controlling the cavity length for the first time. The microcavity is made of a
      silica capillary and two aligned fibers with end faces Au-coated. The Rhodamine
      6G dye solution flowing through the microcavity is pumped by 532 nm wavelength
      laser pulses. Laser emission around 570 nm in the form of TE mode with a
      threshold of about 58  MUJ/pulse is obtained. This work suggests a fiber-based
      convenient approach to achieve wavelength tunability and integration with lab-on
      a-chip systems. 

PMID- 24104826
TI  - Ultralow-loss silicon waveguide crossing using Bloch modes in index-engineered
      cascaded multimode-interference couplers.
AB  - We investigate the loss mechanism in three-moded multimode-interference couplers
      that are the building blocks of a compact and low-loss waveguide crossing
      structure. Broadband silicon waveguide crossing arrays with <0.01  dB insertion
      loss per crossing are proposed using cascaded multimode-interference couplers,
      where lateral subwavelength nanostructures are used to reduce the insertions
      loss. We design and fabricate a 101*101 waveguide crossing array with a pitch of
      3.08 MUm. Insertion loss of ~0.02  dB per crossing and crosstalk <-40  dB at 1550
      nm operating wavelength and a broad transmission spectrum ranging from 1520 to
      1610 nm are experimentally demonstrated. 

PMID- 24104827
TI  - Light-spectrum modification of warm white-light-emitting diodes with 3D colloidal
      photonic crystals to approximate candlelight.
AB  - This study presents the light-spectrum modification of warm white-light-emitting
      diodes (w-WLEDs) with 3D colloidal photonic crystals (3D CPhCs) to approximate
      candlelight. The study measures the angular-resolved transmission properties of
      the w-WLEDs with CPhCs, which exhibit photonic stop bands based on the CPhC
      photonic band structures. The w-WLEDs with 3D CPhCs produce a low correlated
      color temperature of 1963 K, a high color-rendering index of 85, and a luminous
      flux of 22.8 lm (four times that of a candle). This study presents the successful
      development of a novel low-cost technique to produce candlelight w-WLEDs for use
      as an indoor light source. 

PMID- 24104828
TI  - Normal dispersion femtosecond fiber optical parametric oscillator.
AB  - We propose and demonstrate a synchronously pumped fiber optical parametric
      oscillator (FOPO) operating in the normal dispersion regime. The FOPO generates
      chirped pulses at the output, allowing significant pulse energy scaling potential
      without pulse breaking. The output average power of the FOPO at 1600 nm was ~60 
      mW (corresponding to 1.45 nJ pulse energy and ~55% slope power conversion
      efficiency). The output pulses directly from the FOPO were highly chirped (~3  ps
      duration), and they could be compressed outside of the cavity to 180 fs by using
      a standard optical fiber compressor. Detailed numerical simulation was also
      performed to understand the pulse evolution dynamics around the laser cavity. We
      believe that the proposed design concept is useful for scaling up the pulse
      energy in the FOPO using different pumping wavelengths. 

PMID- 24104829
TI  - Demonstration of side coupling to cladding modes through zinc oxide nanorods
      grown on multimode optical fiber.
AB  - A novel concept is introduced that utilizes the scattering properties of zinc
      oxide nanorods to control light guidance and leakage inside optical fibers coated
      with nanorods. The effect of the hydrothermal growth conditions of the nanorods
      on light scattering and coupling to optical fiber are experimentally
      investigated. At optimum conditions, 5% of the incident light is side coupled to
      the cladding modes. This coupling scheme could be used in different applications
      such as distributed sensors and light combing. Implementation of the nanorods on
      fiber provides low cost and controllable nonlithography-based solutions for free
      space to fiber coupling. Higher coupling efficiencies can be achieved with
      further optimization. 

PMID- 24104830
TI  - Generation of tightly compressed solitons with a tunable frequency shift in Raman
      free fibers.
AB  - Optimization of the compression of input N-solitons into robust ultra-narrow
      fundamental solitons, with a tunable up- or downshifted frequency, is proposed in
      photonic crystal fibers free of the Raman effect. Due to the absence of the Raman
      self-frequency shift, these fundamental solitons continue propagation,
      maintaining the acquired frequency, once separated from the input N soliton's
      temporal slot. A universal optimal value of the relative strength of the third
      order dispersion is found, providing the strongest compression of the fundamental
      soliton is found. It depends only on the order of the injected N-soliton. The
      largest compression degree significantly exceeds the analytical prediction
      supplied by the Satsuma-Yajima formula. The mechanism behind this effect, which
      remains valid in the presence of the self-steepening, is explained. 

PMID- 24104831
TI  - Parallel multiphoton microscopy with cylindrically polarized multifocal arrays.
AB  - Diffraction-limited cylindrically polarized multifocal arrays are created in the
      focal region of a high numerical-aperture objective for multiphoton microscopy by
      applying the dynamic phase modulation on an incident light beam. We show that
      this kind of cylindrical-polarization multifocal multiphoton microscopy exhibits
      a parallel imaging capacity but also a dynamic switching-on or -off feature of
      individual focal spots. The parallel multiphoton microscopy results of the
      polarization-sensitive gold nanorods under the illumination of radially or
      azimuthally polarized multifocal arrays allow for the fast determination of the
      orientation of nanorods. 

PMID- 24104832
TI  - High-Q filters with complete transmission by quasi-periodic dielectric
      multilayers.
AB  - A multiple narrow bandpass filter with both high Q factor and complete
      transmission using quasi-periodic Thue-Morse dielectric multilayers is proposed.
      The Q factor of the system increases exponentially with the generation order.
      Even though the Q factor of resonances increases as the generation order of the
      multilayers increases, these resonances are still complete resonances. The number
      of resonance peaks for the bandpass filter of the system also increases as the
      generation order increases. These resonance peaks have a multifractal
      distribution throughout the frequency range, which is different from that in
      traditional periodical multilayers. 

PMID- 24104833
TI  - Origin and control of the subpicosecond pedestal in femtosecond laser systems.
AB  - The picosecond time scale pedestal of a multiterawatt femtosecond laser pulse is
      investigated experimentally and analytically. The origin of the pedestal is
      related to the finite bandwidth of the laser system. By deliberately introducing
      a modulated spectrum with minima that match this limited bandwidth, the pedestal
      can be reduced, with no deleterious effect on the main pulse. Using this
      technique, we experimentally demonstrate a subpicosecond scale order of magnitude
      enhancement of contrast ratio while preserving the energy in the main pulse. 

PMID- 24104834
TI  - Quantum phase transition in fiber-coupled quantum networks.
AB  - We explore the quantum criticality in a one-dimensional quantum network, where
      adjacent nodes are connected by a fiber and each node consists of a cavity doped
      with N two-level atoms. We investigate the phase diagrams for cases of different
      atom numbers on resonance by making use of the mean-field approximation and find
      that both the fidelity and entanglement entropy for the ground state have
      dramatic changes near the critical points. Finally, the photon population
      imbalance of adjacent cavities is analytically explored via the two-node quantum
      network as the forerunner of phase transition. 

PMID- 24104835
TI  - Sub-3-cycle vortex pulses of tunable topological charge.
AB  - Novel types of reflective spiral micro-electro-mechanical systems were used to
      generate few-cycle vortex pulses of variable topological charge from a
      Ti:sapphire laser oscillator. The phase profile of these components was
      controlled by varying the temperature. The temporal properties of the pulses were
      characterized with spatially resolved nonlinear autocorrelation. The beam
      structure resembles a slightly distorted Laguerre-Gaussian distribution. The
      different topological charges were indicated by detecting Poynting-vector maps
      with a programmable Shack-Hartmann sensor of enhanced angular sensitivity. 

PMID- 24104836
TI  - On the temporal behavior of Nd3+ random lasers.
AB  - The temporal dynamics of random laser emission from Nd-doped crystal powders has
      been investigated by using an improved detection device. The precise conditions
      to detect high contrast, fast oscillations are described. The measured period is
      about one order of magnitude shorter than the one given in the literature for
      relaxation oscillations in these materials. The origin of these differences is
      discussed. 

PMID- 24104837
TI  - Long-lived quantum coherence of two-level spontaneous emission models within
      structured environments.
AB  - We investigate the long-lived quantum coherence of two-level spontaneous emission
      models within structured environments. The population of the system under the
      asymptotic non-Markovian dynamics is linked to the spectral density of the
      reservoir through a general functional relation between them. We figure out
      explicitly the preservation of quantum coherence, via notions of entanglement and
      quantum discord, in connection with the spectral parameters of Ohmic class
      reservoirs, and then show how to achieve them optimally. We expect these results
      to contribute to reservoir engineering with the aim of enhancing stationary
      quantum coherence in noisy environments. 

PMID- 24104838
TI  - Narrow linewidth single-frequency terahertz source based on difference frequency
      generation of vertical-external-cavity source-emitting lasers in an external
      resonance cavity.
AB  - We demonstrate a continuous wave, single-frequency terahertz (THz) source
      emitting 1.9 THz. The linewidth is less than 100 kHz and the generated THz output
      power exceeds 100 MUW. The THz source is based on parametric difference frequency
      generation within a nonlinear crystal located in an optical enhancement cavity.
      Two single-frequency vertical-external-cavity source-emitting lasers with
      emission wavelengths spaced by 6.8 nm are phase locked to the external cavity and
      provide pump photons for the nonlinear downconversion. It is demonstrated that
      the THz source can be used as a local oscillator to drive a receiver used in
      astronomy applications. 

PMID- 24104839
TI  - Kapitza homogenization of deep gratings for designing dielectric metamaterials.
AB  - We theoretically investigate the homogenization of the dielectric response to
      transverse electric waves of a transverse grating characterized by the Kapitza
      condition; i.e., the permittivity is rapidly modulated with a modulation depth
      scaling as the large wavelength-to-modulation-period ratio. We show that the
      resulting effective dielectric permittivity, in addition to the standard average
      of the underlying dielectric profile, has a further contribution arising from the
      fast and deep dielectric modulation. Such a contribution turns out to be
      comparable with the other one and hence can provide an additional method for
      designing dielectric metamaterials. As an example, we discuss an effective metal
      to-dielectric transition produced by the Kapitza contribution obtained by
      changing the grating depth, a remarkable result for applications involving
      epsilon-near-zero metamaterial design. 

PMID- 24104840
TI  - Stable and flexible ring-shaped optical-lattice generation by use of axially
      symmetric polarization elements.
AB  - To overcome a trade-off issue between stability and flexibility in the generation
      of ring-shaped optical lattices, we proposed and demonstrated a novel generation
      method by using axially symmetric polarization elements. While two optical
      vortices were coaxially generated, electrically controlled phase difference
      between them by an electro-optic modulator enabled a precise rotation of the
      lattice. Our method has the capability to fulfill the high stability and rapid
      rotation. 

PMID- 24104841
TI  - Frequency stability of a 10 GHz optical frequency comb from a semiconductor-based
      mode-locked laser with an intracavity 10,000 finesse etalon.
AB  - An optical frequency comb is constructed using a semiconductor gain medium with a
      fiber-coupled external cavity and stabilized to an intracavity 10,000 finesse
      etalon, which is temperature stabilized and held in a vacuum chamber at 10(-6) 
      Torr. Optical frequency stability measurements show that the comb has a reduced
      sensitivity to environmental fluctuations. An upper limit on the optical
      frequency variation of 100 kHz over >12  min of continuous operation is measured
      using a real-time spectrum analyzer. This measurement is limited by the linewidth
      of the reference source, and further measurements with a frequency counter show a
      fractional deviation of 2*10(-11) at 50 ms. Furthermore, out-of-band ASE
      rejection is shown to be >36  dB, a tenfold improvement over that of a laser with
      a 1000 finesse FPE.

PMID- 24104842
TI  - High temperature luminescence of Dy3+ in crystalline silicon in the optical
      communication and eye-safe spectral regions.
AB  - We report on photoluminescence in the 1.3 and 1.7 MUm spectral ranges in silicon
      doped with dysprosium. This is attributed to the Dy3+ internal transitions
      between the second Dy3+ excited state and the ground state, and between the third
      Dy3+ excited state and the ground state. Luminescence is achieved by Dy
      implantation into Si substrates codoped with boron, to form dislocation loops,
      and show a strong dependence on fabrication process. The spectra consist of
      several sharp lines with the strongest emission at 1736 nm, observed up to 200 K.
      No Dy3+ luminescence is observed in samples without B codoping, showing the
      paramount importance of dislocation loops to enable the Dy emission.

PMID- 24104843
TI  - Arrayed free space continuous-wave terahertz photomixers.
AB  - We present free space coherent arrays of continuous-wave terahertz (THz)
      photomixers and compare the results to on-chip arrays. By altering the relative
      phases of the exciting laser signals, the relative THz phase between the array
      elements can be tuned, allowing for beam steering. In addition, the constructive
      interference of the emission of N elements leads to an increase of the focal
      intensity by a factor of N2 while reducing the beam width by ~N(-1), below the
      diffraction limit of a single source. Such array architectures strongly improve
      the THz power distribution for stand-off spectroscopy and imaging systems while
      providing a huge bandwidth at the same time. We demonstrate this by beam profiles
      generated by a 2*2 and a 4*1 array for a transmission distance of 4.2 m. Spectra
      between 70 GHz and 1.1 THz have been recorded with these arrays.

PMID- 24104844
TI  - Enhanced light-matter interaction at nanoscale by utilizing high-aspect-ratio
      metallic gratings.
AB  - We report the design, fabrication, and experimental characterization of high
      aspect-ratio metallic gratings integrated with nanoscale semiconductor
      structures, which enable efficient light-matter interaction at the nanoscale over
      interaction lengths as long as two times of the effective optical wavelength. The
      efficient light-matter interaction at the nanoscale is enabled by excitation of
      the guided modes of subwavelength slab waveguides formed by the high-aspect-ratio
      metallic gratings. By controlling the height of the high-aspect-ratio gratings,
      the wavelength of the guided modes through the nanoscale semiconductor structures
      is determined. 

PMID- 24104845
TI  - Nanowire photovoltaic efficiency enhancement using plasmonic coupled nano-fractal
      antennas.
AB  - We suggest the use of nano-fractal antennas for plasmonic coupling to enhance
      nanowire (NW) photovoltaic power conversion efficiency. Silicon radial pn
      junction NWs positioned inside Apollonian and Sierpinski nano-fractal antennas
      are simulated with different topologies and NW lengths. An enhancement in power
      conversion efficiency ranging from 12% to up to 24% over the same NW without
      antenna case is achieved. 

PMID- 24104846
TI  - Amplitude-phase retrieval attack free cryptosystem based on direct attack to
      phase-truncated Fourier-transform-based encryption using a random amplitude mask.
AB  - We propose a simple amplitude-phase retrieval attack free cryptosystem based on
      direct attack to phase-truncated Fourier-transform-based encryption using a
      random amplitude mask (RAM). The RAM that is not saved during the encryption
      provides extremely high security for the two private keys, and no iterative
      calculations are involved in the nonlinear encryption process. Lack of enough
      constraints makes the specific attack based on iterative amplitude-phase
      retrieval algorithms unusable. Numerical simulation results are given for testing
      the validity and security of the proposed approach. 

PMID- 24104847
TI  - THz-wave sensing via pump and signal wave detection interacted with evanescent
      THz waves.
AB  - We report a novel sensing technique that uses an evanescent terahertz (THz) wave,
      without detecting the THz wave directly. When a THz wave generated by Cherenkov
      phase matching via difference frequency generation undergoes total internal
      reflection, the evanescent THz wave is subject to a phase change and an amplitude
      decrease. The reflected THz wave, under the influence of the sample, interferes
      with the propagating THz wave and the changing electric field of the THz wave
      interacts with the electric field of the pump waves. We demonstrate a sensing
      technique for detecting changes in the electric field of near-infrared light,
      transcribed from changes in the electric field of a THz wave. 

PMID- 24104848
TI  - Dual-wavelength laser speckle imaging to simultaneously access blood flow, blood
      volume, and oxygenation using a color CCD camera.
AB  - We developed a dual-wavelength laser speckle imaging system using a single
      industrial-grade color CCD camera with Bayer filters to simultaneously image
      changes in blood flow, blood volume, and oxygenation. One frame of a color image
      recorded with dual-wavelength laser illumination provides not only the intensity
      fluctuation of the speckle pattern, but also the dual-wavelength optical
      reflectance signal. The method was validated using a tissue phantom and cuff
      ischemia experiments in the human arm. This system achieves complete time
      synchronization, unlike conventional time-sharing systems. Compared with a
      multicamera system, it also avoids the problem of image registration and can be
      less expensive. 

PMID- 24104849
TI  - Correlated photons in one-dimensional waveguides.
AB  - We study two-photon transport in a one-dimensional waveguide with a side-coupled
      two-level system. Depending on the momentum of the incoming photons, we find that
      the nature of the scattering process changes considerably. We further show that
      bunching behavior can be found in the scattered light. As a result, we find that
      the waveguide dispersion has a strong influence on the photon correlations. By
      modifying the momentum of the pulse, the nature of the correlations can therefore
      be altered or optimized. 

PMID- 24104850
TI  - Efficient L1 regularization-based reconstruction for fluorescent molecular
      tomography using restarted nonlinear conjugate gradient.
AB  - For the ill-posed fluorescent molecular tomography (FMT) inverse problem, the L1
      regularization can protect the high-frequency information like edges while
      effectively reduce the image noise. However, the state-of-the-art L1
      regularization-based algorithms for FMT reconstruction are expensive in memory,
      especially for large-scale problems. An efficient L1 regularization-based
      reconstruction algorithm based on nonlinear conjugate gradient with restarted
      strategy is proposed to increase the computational speed with low memory
      consumption. The reconstruction results from phantom experiments demonstrate that
      the proposed algorithm can obtain high spatial resolution and high signal-to
      noise ratio, as well as high localization accuracy for fluorescence targets. 

PMID- 24104851
TI  - Vector optical fields with bipolar symmetry of linear polarization.
AB  - We focus on a new kind of vector optical field with bipolar symmetry of linear
      polarization instead of cylindrical and elliptical symmetries, enriching members
      of family of vector optical fields. We design theoretically and generate
      experimentally the demanded vector optical fields and then explore some novel
      tightly focusing properties. The geometric configurations of states of
      polarization provide additional degrees of freedom assisting in engineering the
      field distribution at the focus to the specific applications such as lithography,
      optical trapping, and material processing. 

PMID- 24104852
TI  - Faster and better.

PMID- 24104853
TI  - Clinical outcome of penetrating keratoplasty in patients 5 years or younger:
      peters anomaly versus sclerocornea.
AB  - PURPOSE: To investigate and compare the clinical outcome of primary penetrating
      keratoplasty in pediatric patients with Peters anomaly and sclerocornea. METHODS:
      Medical records of 20 eyes of 18 patients with Peters anomaly or sclerocornea who
      underwent primary penetrating keratoplasty when they were 5 years or younger were
      reviewed. The survival rates and median survival times of corneal grafts were
      evaluated to determine the surgical outcome. Demographics of patients, the
      preoperative characteristics of recipient eyes, surgical procedures, causes of
      graft failure, and postoperative complications were analyzed to identify the
      factors affecting graft survival. RESULTS: A total of 20 penetrating
      keratoplasties were performed in 18 patients. Eight patients had Peters anomaly,
      and 10 patients had sclerocornea. Overall, 50% of corneal grafts survived during
      the follow-up of 92.7 +/- 10 months. The graft survival was 65% at 6 months and
      remained 50% at 12 months, 2 years, and 5 years after surgery. The mean survival
      time and survival rate were significantly different between patients with Peters
      anomaly and those with sclerocornea (the survival time, 135.6 +/- 17.9 vs. 36.4
      +/- 16.1 months, P = 0.014; the survival rate, 87.5% vs. 25.0%, P = 0.02). The
      presence of opacity or vascularization in the limbus and in the peripheral cornea
      and the diameter of the recipient cornea were significantly correlated with graft
      failure. CONCLUSIONS: Penetrating keratoplasty in patients who were 5 years or
      younger had an excellent surgical outcome in patients with Peters anomaly,
      whereas the graft survival was poor in patients with sclerocornea.

PMID- 24104854
TI  - 18F-FDG PET-CT imaging in the neoadjuvant setting for stages II-III breast
      cancer: association of loco-regional SUVmax with classical prognostic factors.
AB  - AIM: Classical prognostic and predictive factors serve to predict outcome and
      response to neoadjuvant treatment in stage II and III breast cancer. The purpose
      is to determine the relation between the SUVmax of the locoregional disease with
      these classical prognostic factors. METHODS: A prospective study including 43
      stage II and III breast cancer patients was performed. In all the patients, two
      18F-FDG PET-CT studies were performed before and after neoadjuvant chemotherapy.
      After this treatment, surgery and adjuvant treatment were carried out. To combine
      the information of the locoregional disease, the SUVmax of the lesion (tumor or
      abnormal lymphnodes) with the highest uptake was used. SUVmax and prognostic
      factors were studied with the Kruskal-Wallis non-parametric test and with the
      Mann-Whitney U. RESULTS: A statistically significant association between elevated
      SUVmax value and absence of estrogen receptors (ER) expression (16 vs.. 10;
      P<0.019) was found. Locorregional disease with positive HER2 phenotype had a
      statistically significant SUVmax value greater than Luminal A (estrogen and/or
      progesterone positive receptors with Ki67<15%) and B (estrogen and/or
      progesterone positive receptors with Ki67>=to 15%) (13.4 vs. 7.9 and 8.9; P<0.022
      and P<0.024, respectively). Triple negative phenotype disease had higher SUVmax
      than Luminal A and B (15.4; P<0.030 and P<0.038). Positive correlation between
      the percentage of the Ki67 Proliferation Index and SUVmax (P<0.007) was
      demonstrated. High grade disease had a higher SUVmax than low grade (P<0.004).
      CONCLUSION: Locorregional SUVmax is associated to prognostic and predictive
      factors and reaffirms the utility of PET-CT as a tool in the common clinical
      practice.

PMID- 24104855
TI  - Synthesis and characterisation of ruthenium dihydrogen complexes and their
      reactivity towards B-H bonds.
AB  - In this paper the synthesis and characterisation of ruthenium dihydrogen
      complexes bearing rigid aliphatic PNP pincer-type ligands are described. As one
      result hydride complexes were synthesised in good to high yields by a one-pot
      direct hydrogenation reaction. As another finding the dihydrogen complex,
      stabilised with a N-Me group in the ligand frame, can be converted with
      dimethylamine borane into a rare sigma-boron complex [RuH2(BH3)(Me-PNP)] with
      rapid B-N decoupling. Additionally, we present the first mass spectrometric
      analysis of the synthesised sigma-complexes via liquid injection field
      desorption/ionisation technique (LIFDI-MS). 

PMID- 24104856
TI  - Evidence-based patient information programme in early multiple sclerosis: a
      randomised controlled trial.
AB  - OBJECTIVE: To evaluate the efficacy of an evidence-based patient information
      programme aiming to increase informed choice in patients with early multiple
      sclerosis (MS). BACKGROUND: Patients with early MS face a number of uncertainties
      concerning diagnosis, prognosis and effectiveness of immunotherapy. Prior studies
      suggest that evidence-based patient information combined with group education can
      promote informed choice in MS patients. METHODS: A 12-month, six-centre, double
      blind randomised controlled clinical trial with 192 patients with a diagnosis of
      confirmed relapsing-remitting MS or clinical isolated syndrome in Germany. A 4-h
      interactive evidence-based educational programme was compared with a 4-h MS
      specific stress management programme. The primary endpoint was informed choice
      after 6 months comprising risk knowledge and congruency between attitude towards
      immunotherapy and actual immunotherapy uptake. Secondary endpoints included
      autonomy preference, decision autonomy, decisional conflict and satisfaction,
      anxiety and depression, and number of immunotherapies. RESULTS: For the primary
      endpoint, a significant difference was shown with 50 of 85 (59%) participants in
      the intervention group achieving informed choice after 6 months compared with 18
      of 89 (20%) in the control group (OR 0.2 (95% CI 0.1 to 0.4), p<0.001). Four
      weeks after the intervention, more participants in the intervention group showed
      good risk knowledge (difference between groups 39% (95% CI 26% to 53%), p<0.001).
      There were no significant differences between groups for attitude towards
      immunotherapy and for immunotherapy uptake. There were trends towards increased
      autonomy preference after the intervention and increased adherence to
      immunotherapies in the intervention group. CONCLUSIONS: The intervention
      significantly increased informed choice and relevant risk knowledge without
      negative side effects.

PMID- 24104857
TI  - Current transport mechanism at metal-semiconductor nanoscale interfaces based on
      ultrahigh density arrays of p-type NiO nano-pillars.
AB  - The present work focuses on a qualitative analysis of localised I-V
      characteristics based on the nanostructure morphology of highly dense arrays of p
      type NiO nano-pillars (NiO-NPs). Vertically aligned NiO-NPs have been grown on
      different substrates by using a glancing angle deposition (GLAD) technique. The
      preferred orientation of as grown NiO-NPs was controlled by the deposition
      pressure. The NiO-NPs displayed a polar surface with a microscopic dipole moment
      along the (111) plane (Tasker's type III). Consequently, the crystal plane
      dependent surface electron accumulation layer and the lattice disorder at the
      grain boundary interface showed a non-uniform current distribution throughout the
      sample surface, demonstrated by a conducting AFM technique (c-AFM). The variation
      in I-V for different points in a single current distribution grain (CD-grain) has
      been attributed to the variation of Schottky barrier height (SBH) at the metal
      semiconductor (M-S) interface. Furthermore, we observed that the strain produced
      during the NiO-NPs growth can modulate the SBH. Inbound strain acts as an
      external field to influence the local electric field at the M-S interface causing
      a variation in SBH with the NPs orientation. This paper shows that vertical
      arrays of NiO-NPs are potential candidates for nanoscale devices because they
      have a great impact on the local current transport mechanism due to its
      nanostructure morphology. 

PMID- 24104858
TI  - Gate control of electronic phases in a quarter-filled manganite.
AB  - Electron correlation often produces a variety of electrically insulating states
      caused by self-organization of electrons, which are particularly stable at
      commensurate fillings. Although collapsing such ordered states by minute external
      stimuli has been a key strategy toward device applications, it is difficult to
      access their true electronic phase boundaries due to the necessity of fine-tuning
      of material parameters. Here, we demonstrate the ambipolar resistance switching
      in Pr(1-x)Sr(x)MnO3 thin films (x = 0.5; an effectively 1/4-filled state) by
      quasi-continuous control of the doping level x and band-width W using gate
      voltage and magnetic field, enabled by the extreme electric-field formed at the
      nanoscale interface generated in an electrolyte-gated transistor. An
      electroresistance peak with unprecedented steepness emerges on approaching a
      critical point in the x-W phase diagram. The technique opens a new route to Mott
      insulator based transistors and to discovering singularities hitherto unnoticed
      in conventional bulk studies of strongly correlated electron systems.

PMID- 24104859
TI  - Fusion reactions initiated by laser-accelerated particle beams in a laser
      produced plasma.
AB  - The advent of high-intensity-pulsed laser technology enables the generation of
      extreme states of matter under conditions that are far from thermal equilibrium.
      This in turn could enable different approaches to generating energy from nuclear
      fusion. Relaxing the equilibrium requirement could widen the range of isotopes
      used in fusion fuels permitting cleaner and less hazardous reactions that do not
      produce high-energy neutrons. Here we propose and implement a means to drive
      fusion reactions between protons and boron-11 nuclei by colliding a laser
      accelerated proton beam with a laser-generated boron plasma. We report proton
      boron reaction rates that are orders of magnitude higher than those reported
      previously. Beyond fusion, our approach demonstrates a new means for exploring
      low-energy nuclear reactions such as those that occur in astrophysical plasmas
      and related environments. 

PMID- 24104860
TI  - Assembly of catalase-based bioconjugates for enhanced anticancer efficiency of
      photodynamic therapy in vitro.
AB  - An oxygen generation core-shell structure uploading rose bengal has been
      fabricated by covalent assembly of catalase and alginate dialdehyde via Schiff's
      base. The composite can catalyze the decomposition of intracellular H2O2 to
      increase the concentration of O2, which effectively enhances the anticancer
      efficiency of photodynamic therapy in vitro. 

PMID- 24104861
TI  - Cr(VI) imposed toxicity in maize seedlings assessed in terms of disruption in
      carbohydrate metabolism.
AB  - The present study examined the toxic effects of Cr(VI; 100, 250 and 500 MUM) in
      maize seedlings by investigating the changes in carbohydrate metabolism after 48,
      96, and 144 h of exposure. Cr-stress results in severe alterations in the
      contents of carbohydrates and reducing sugars and the activities of carbohydrate
      metabolizing enzymes, amylases, phosphatases and phosphorylases, and invertases
      in maize seedlings. Under Cr stress, the contents of carbohydrates and reducing
      sugars declined in roots, whereas an increase was noticed in leaves. The
      catalytic activity of carbohydrate metabolizing enzymes, except invertases, in
      roots declined in the presence of Cr(VI) in a concentration- and exposure time
      dependent manner. In contrast, the activities of these enzymes were enhanced in
      leaves under Cr(VI) stress. The activity of invertases increased with increasing
      amount of Cr(VI) but declined with an increase in the time interval. In
      conclusion, our results show that carbohydrate metabolism is severely affected
      under Cr(VI) toxicity. The study suggests that Cr-induced perturbations in the
      carbohydrate metabolism are one of the factors resulting in growth inhibition
      under Cr(VI) stress.

PMID- 24104862
TI  - Deep transcriptome sequencing of rhizome and aerial-shoot in Sorghum propinquum.
AB  - Transcriptomic data for Sorghum propinquum, the wild-type sorghum, are limited in
      public databases. S. propinquum has a subterranean rhizome and transcriptome data
      will help in understanding the molecular mechanisms underlying rhizome formation.
      We sequenced the transcriptome of S. propinquum aerial-shoot and rhizome using an
      Illumina platform. More than 70 % of the genes in the S. propinquum genome were
      expressed in aerial-shoot and rhizome. The expression patterns of 1963 and 599
      genes, including transcription factors, were specific or enriched in aerial-shoot
      and rhizome respectively, indicating their possible roles in physiological
      processes in these tissues. Comparative analysis revealed several cis-elements,
      ACGT box, GCCAC, GATC and TGACG box, which showed significantly higher abundance
      in aerial-shoot-specific genes. In rhizome-specific genes MYB and ROOTMOTIFTAPOX1
      motifs, and 10 promoter and cytokinin-responsive elements were highly enriched.
      Of the S. propinquum genes, 27.9 % were identified as alternatively spliced and
      about 60 % of the alternative splicing (AS) events were tissue-specific,
      suggesting that AS played a crucial role in determining tissue-specific cellular
      function. The transcriptome data, especially the co-localized rhizome-enriched
      expressed transcripts that mapped to the publicly available rhizome-related
      quantitative trait loci, will contribute to gene discovery in S. propinquum and
      to functional studies of the sorghum genome. Deep transcriptome sequencing
      revealed a clear difference in the expression patterns of genes between aerial
      shoot and rhizome in S. propinquum. This data set provides essential information
      for future studies into the molecular genetic mechanisms involved in rhizome
      formation. 

PMID- 24104863
TI  - Identification of a novel type of WRKY transcription factor binding site in
      elicitor-responsive cis-sequences from Arabidopsis thaliana.
AB  - Using a combination of bioinformatics and synthetic promoters, novel elicitor
      responsive cis-sequences were discovered in promoters of pathogen-upregulated
      genes from Arabidopsis thaliana. One group of functional sequences contains the
      conserved core sequence GACTTTT. This core sequence and adjacent nucleotides are
      essential for elicitor-responsive gene expression in a parsley protoplast system.
      By yeast one-hybrid screening, WRKY70 was selected with a cis-sequence harbouring
      the core sequence GACTTTT but no known WRKY binding site (W-box). Transactivation
      experiments, mutation analyses, and electrophoretic mobility shift assays
      demonstrate that the sequence CGACTTTT is the binding site for WRKY70 in the
      investigated cis-sequence and is required for WRKY70-activated gene expression.
      Using several cis-sequences in transactivation experiments and binding studies,
      the CGACTTTT sequence can be extended to propose YGACTTTT as WRKY70 binding site.
      This binding site, designated WT-box, is enriched in promoters of genes
      upregulated in a WRKY70 overexpressing line. Interestingly, functional WRKY70
      binding sites are present in the promoter of WRKY30, supporting recent evidence
      that both factors play a role in the same regulatory network. 

PMID- 24104865
TI  - ["About how much do you think a doctor in general practice earns, and how much
      should a doctor earn?" Results of a survey in Germany's population].
AB  - BACKGROUND: As a result of divergent information about doctors' income in the
      media, the general public might consider medical doctors to be either over- or
      underpaid. In the ALLBUS 2010 survey the general public was asked to estimate the
      incomes of general practitioners and other professions and to state how much, in
      their view, they should earn. METHOD: The respondents were chosen using a 2-stage
      random sample (1. communities; 2. population register) and interviewed at home.
      Data were collected via computer administered self-interview. RESULTS: 1,388
      persons took part; 39.9% consider general practitioners to be underpaid, 39.0%
      consider their earnings fair. On average, general practitioners' income was
      estimated at ? 6,711 gross per month and respondents thought that they should
      earn ? 7,050. Chairmen of large national corporations are considered overpaid by
      80.3% and cabinet ministers by 71.9% of the respondents. Shop assistants and
      unskilled workers are considered underpaid by 79.1% and 73.7% respectively.
      DISCUSSION: The estimates of general practitioners' income vary widely, but only
      21.1% of the population considers them overpaid. The means of the estimated
      income and the "should-earn" income of general practitioners are actually quite
      close, but most respondents think that unskilled workers and shop assistants
      should earn more.

PMID- 24104864
TI  - Incidence and prognostic impact of KRAS and BRAF mutation in patients undergoing
      liver surgery for colorectal metastases.
AB  - BACKGROUND: Molecular biomarkers offer the potential for refining prognostic
      determinants in patients undergoing cancer surgery. Among patients with
      colorectal cancer, KRAS and BRAF are important biomarkers, but their role in
      patients undergoing surgical therapy for liver metastases is unknown. In this
      study, the incidence and prognostic significance of KRAS and BRAF mutations were
      determined in patients undergoing surgical therapy of colorectal liver metastases
      (CRLM). METHODS: KRAS and BRAF analysis was performed on 202 patients undergoing
      surgery for CRLM between 2003 and 2008. Tumor samples were analyzed for somatic
      mutations using sequencing analysis (KRAS, codon12/13, BRAF, V600E). The
      frequency of mutations was ascertained, and their impact on outcome was
      determined relative to other clinicopathologic factors. RESULTS: KRAS gene
      mutations were detected in 58/202 patients (29%). In contrast, mutation in the
      BRAF gene was identified in very low frequency in this surgical cohort, found in
      only 4/202 (2%) patients. On multivariate analysis, KRAS mutation was associated
      with worse survival (hazard ratio [HR], 1.99; 95% confidence interval [CI], 1.21
      3.26), as well as recurrence risk (HR, 1.68; 95% CI, 1.04-2.70). Although other
      clinicopathologic features, including tumor number, carcinoembryonic antigen, and
      primary stage were also associated with survival, KRAS status remained
      independently predictive of outcome. The low incidence of BRAF mutation limited
      assessment of its prognostic impact. CONCLUSION: Whereas KRAS mutations were
      found in approximately one third of patients, BFAF mutations were found in only
      2% of patients undergoing surgery for CRLM. KRAS status was an independent
      predictor of overall and recurrence-free survival. Molecular biomarkers such as
      KRAS may help to refine our prognostic assessment of patients undergoing surgical
      therapy for CRLM.

PMID- 24104866
TI  - [The health-care situation in outpatient psychiatry--results of a survey among
      members of the Germany Association of Psychotherapists (DPtV)].
AB  - BACKGROUND: Mental-health problems are of increasing importance in the German
      population. Nonetheless there is a lack of data concerning outpatient
      psychotherapeutic care, especially with a focus on psychotherapy sessions
      approved by social health insurances and performed by psychological
      psychotherapists and paediatric psychotherapists. METHODS: The study presents the
      results of a survey among all members of the German Association of
      Psychotherapists (DPtV) and is based on questionnaires filled in by 2,497
      psychotherapists (return rate 33.3%). The assessment is based on the therapists'
      data without an external validation. Main topics of the survey were
      characteristics of the supply of psychotherapeutic care, therapeutic time
      contingents per patient and their utilisation and demographic and socio-economic
      features of patients. Evaluating the survey, the results were analysed overall
      and by groups of therapists varying in demographic features, professional
      qualifications and regional criteria, using bivariate as well as multivariate
      methods. RESULTS: The study provides evidence indicating an underprovision of
      outpatient psychotherapeutic care. Psychotherapists who use a waiting list
      reported average waiting times of more than 2.5 months. Additionally there are
      differences in psychotherapeutic care between various patient groups. In regions
      with lower population density we found less provision of psychotherapeutic care
      compared to regions with higher population density. Taking into account
      epidemiological data, the study indicates that the participation of men, persons
      of older age and patients with lower levels of education in psychotherapeutic
      care is below average. CONCLUSION: The results suggest a considerable degree of
      underprovision and inadequate provision of outpatient psychotherapeutic care.
      With regard to special population groups, further research is necessary to
      identify utilisation barriers towards psychotherapy.

PMID- 24104868
TI  - Extramedullary haematopoiesis presenting with paraparesis.

PMID- 24104869
TI  - Bi-tangential hybrid IMRT for sparing the shoulder in whole breast irradiation.
AB  - BACKGROUND AND PURPOSE: A bi-tangential technique is proposed to reduce undesired
      doses to the shoulder produced by standard tangential irradiation. PATIENTS AND
      METHODS: A total of 6 patients affected by shoulder pain and reduced functional
      capacity after whole-breast irradiation were retrospectively analysed. The
      standard tangential plan used for treatment was compared with (1) a single bi
      tangential plan where, to spare the shoulder, the lateral open tangent was split
      into two half-beams at isocentre, with the superior portion rotated by 10-20
      degrees  medially with respect to the standard lateral beam; (2) a double bi
      tangential plan, where both the tangential open beams were split. The planning
      target volume (PTV) coverage and the dose to the portion of muscles and axilla
      included in the standard tangential beams were compared. RESULTS: PTV95 % of
      standard plan (91.9 +/- 3.8) was not significantly different from single bi
      tangential plan (91.8 +/- 3.4); a small but significant (p < 0.01) decrease was
      observed with the double bi-tangential plan (90.1 +/- 3.7). A marked dose
      reduction to the muscle was produced by the single bi-tangential plan around 30
      40 Gy. The application of the double bi-tangential technique further reduced the
      volume receiving around 20 Gy, but did not markedly affect the higher doses. The
      dose to the axilla was reduced both in the single and the double bi-tangential
      plans. CONCLUSION: The single bi-tangential technique would have been able to
      reduce the dose to shoulder and axilla, without compromising target coverage.
      This simple technique is valuable for irradiation after axillary lymph node
      dissection or in patients without dissection due to negative or low-volume
      sentinel lymph node disease.

PMID- 24104870
TI  - Localization and quantification of the delivered dose to the spinal cord.
      Predicting actual delivered dose during daily MVCT image-guided tomotherapy.
AB  - PURPOSE: The goal of the present work was to localize and quantify the actual
      delivered dose to the cervical spinal cord (SC) during head and neck cancer (H&N)
      treatment. MATERIALS AND METHODS: A total of 20 H&N patients treated with
      bilateral nodal irradiation with helical tomotherapy (HT) were analyzed. Daily
      MVCTs were performed for image guidance. On every second MVCT, the SC was
      recontoured and the delivered dose for the given treatment fraction (12 fractions
      per patient) was recalculated. The magnitude and localization (CT slice, spinal
      cord quadrant) of the Dmax to the SC on the planning CT (PLAN-Dmax) and of the
      actual delivered Dmax (a-Dmax) were analyzed. RESULTS: A systematic deviation
      from the PLAN-Dmax was observed in 15 out of 20 patients. Large interpatient
      variability of the a-Dmax in the spinal cord was noted (4.5+/-4%). Intrapatient
      variability in a-Dmax was, generally, minimal (1.8+/-2.7%). Throughout the
      treatment course, the higher dose was located in the same CT slices and in the
      same quadrants (anterior right and anterior left) for the same patient.
      CONCLUSION: Exact localization and quantification of the change of the a-Dmax can
      be made for most patients by recalculating the dose on the daily IGRT-MVCTs. This
      could be helpful in assessing whether replanning is necessary in patients with
      doses close to the known tolerance doses of the spinal cord.

PMID- 24104871
TI  - Brain metastasis from non-small cell lung cancer (NSCLC): prognostic importance
      of the number of involved extracranial organs.
AB  - BACKGROUND AND PURPOSE: This study investigated the potential prognostic value of
      the number of involved extracranial organs in patients with brain metastasis from
      non-small cell lung cancer (NSCLC). MATERIAL AND METHODS: A total of 472 patients
      who received whole-brain radiotherapy (WBRT) alone with 5 * 4 Gy or 10 * 3 Gy for
      brain metastasis from NSCLC were included in this retrospective study. In
      addition to the number of involved extracranial organs, 6 further potential
      prognostic factors were investigated including WBRT regimen, age, gender,
      Karnofsky Performance Score (KPS), number of brain metastases, and the interval
      from cancer diagnosis to WBRT. Subgroup analyses were performed for patients with
      metastatic involvement of one (lung vs. bone vs. other metastasis) and two (lung
      + bone vs. lung+lymph nodes vs. other combinations) extracranial organs. RESULTS:
      The survival rates at 6 months of the patients with involvement of 0, 1, 2, 3,
      and >= 4 extracranial organs were 52, 27, 17, 4, and 14%, respectively (p<0.001).
      On multivariate analysis, the number of involved extracranial organs remained
      significant (risk ratio 1.32; 95% confidence interval 1.19-1.46; p<0.001). Age
      <65 years (p=0.004), KPS >= 70 (p<0.001), and only 1-3 brain metastases (p=0.022)
      were also significantly associated with survival in the multivariate analysis. In
      the separate analyses of patients with involvement of one and two extracranial
      organs, survival was not significantly different based on the pattern of
      extracranial organ involvement. CONCLUSION: The number of involved extracranial
      organs is an independent prognostic factor of survival in patients with brain
      metastasis from NSCLC, irrespective of the pattern of extracranial organ
      involvement.

PMID- 24104872
TI  - Brain metastasis. Prognostic value of the number of involved extracranial organs.
AB  - BACKGROUND AND PURPOSE: This study was performed to evaluate the prognostic role
      for survival of the number and the type of involved extracranial organs in
      patients with brain metastasis. MATERIAL AND METHODS: The data of 1146 patients
      who received whole-brain radiotherapy (WBRT) alone for brain metastasis have been
      retrospectively analyzed. In addition to the number of involved extra cranial
      organs, seven potential prognostic factors were investigated including WBRT
      regimen, age, gender, Karnofsky Performance Score (KPS), primary tumor type,
      number of brain metastases, and the interval from cancer diagnosis to WBRT.
      Additionally, subgroup analyses were performed for patients with involvement of
      one (lung vs. bone vs. liver vs. other metastasis) and two (lung + lymph nodes
      vs. lung + bone vs. lung + liver vs. liver + bone vs. other combinations)
      extracranial organs. RESULTS: The 6-month survival rates for the involvement of
      0, 1, 2, 3, and >=4 extracranial organs were 51, 30, 16, 13, and 10%,
      respectively (p<0.001). On multivariate analysis, the number of involved
      extracranial organs maintained significance (risk ratio 1.26; 95% confidence
      interval 1.18-1.34; p<0.001). According to the multivariate analysis, age
      (p<0.001), gender (p=0.002), and KPS (p<0.001) were also independent prognostic
      factors for survival. In the subgroup analyses of patients with involvement of
      one and two extracranial organs, survival was not significantly different based
      on the extracranial organ involved. CONCLUSION: The number of involved
      extracranial organs proved to be an independent prognostic factor in patients
      with brain metastasis, regardless of the organs involved. The number of involved
      extracranial organs should be considered in future trials designed for patients
      with brain metastasis.

PMID- 24104873
TI  - [Prediction of local-regional failures in urothelial carcinoma of the bladder
      after radical cystectomy. A novel risk stratification].

PMID- 24104874
TI  - Hepatocellular carcinoma mimicking an atrial mixoma.

PMID- 24104875
TI  - Early short-term doxycycline therapy in patients with acute myocardial infarction
      and left ventricular dysfunction to prevent the ominous progression to adverse
      remodelling: the TIPTOP trial.
AB  - AIMS: Experimental studies suggest that doxycycline attenuates post-infarction
      remodelling and exerts protective effects on myocardial ischaemia/reperfusion
      injury. However, the effects of the drug in the clinical setting are unknown. The
      aim of this study was to examine the effect of doxycycline on left ventricular
      (LV) remodelling in patients with acute ST-segment elevation myocardial
      infarction (STEMI) and LV dysfunction. METHODS AND RESULTS: Open-label,
      randomized, phase II trial. Immediately after primary percutaneous coronary
      intervention, patients with STEMI and LV ejection fraction < 40% were randomly
      assigned to doxycycline (100 mg b.i.d. for 7 days) in addition to standard
      therapy, or to standard care. The echo LV end-diastolic volumes index (LVEDVi)
      was determined at baseline and 6 months. (99m)Tc-Sestamibi-single-photon emission
      computed tomography infarct size and severity were assessed at 6 months. We
      calculated a sample size of 110 patients, assuming that doxycycline may reduce
      the increase in the LVEDVi from baseline to 6 months > 50% compared with the
      standard therapy (statistical power > 80% with a type I error = 0.05). The 6
      month changes in %LVEDVi were significant smaller in the doxycycline group than
      in the control group [0.4% (IQR: -16.0 to 14.2%) vs.13.4% (IQR: -7.9 to 29.3%); P
      = 0.012], as well as infarct size [5.5% (IQR: 0 to 18.8%) vs. 10.4% (IQR: 0.3 to
      29.9%) P = 0.052], and infarct severity [0.53 (IQR: 0.43-0.62) vs. 0.44 (IQR:
      0.29-0.60), P = 0.014], respectively. CONCLUSION: In patients with acute STEMI
      and LV dysfunction, doxycycline reduces the adverse LV remodelling for comparable
      definite myocardial infarct size (NCT00469261).

PMID- 24104876
TI  - High population prevalence of cardiac troponin I measured by a high-sensitivity
      assay and cardiovascular risk estimation: the MORGAM Biomarker Project Scottish
      Cohort.
AB  - AIMS: Our aim was to test the prediction and clinical applicability of high
      sensitivity assayed troponin I for incident cardiovascular events in a general
      middle-aged European population. METHODS AND RESULTS: High-sensitivity assayed
      troponin I was measured in the Scottish Heart Health Extended Cohort (n = 15 340)
      with 2171 cardiovascular events (including acute coronary heart disease and
      probable ischaemic strokes), 714 coronary deaths (25% of all deaths), 1980
      myocardial infarctions, and 797 strokes of all kinds during an average of 20
      years follow-up. Detection rate above the limit of detection (LoD) was 74.8% in
      the overall population and 82.6% in men and 67.0% in women. Troponin I assayed by
      the high-sensitivity method was associated with future cardiovascular risk after
      full adjustment such as that individuals in the fourth category had 2.5 times the
      risk compared with those without detectable troponin I (P < 0.0001). These
      associations remained significant even for those individuals in whom levels of
      contemporary-sensitivity troponin I measures were not detectable. Addition of
      troponin I levels to clinical variables led to significant increases in risk
      prediction with significant improvement of the c-statistic (P < 0.0001) and net
      reclassification (P < 0.0001). A threshold of 4.7 pg/mL in women and 7.0 pg/mL in
      men is suggested to detect individuals at high risk for future cardiovascular
      events. CONCLUSION: Troponin I, measured with a high-sensitivity assay, is an
      independent predictor of cardiovascular events and might support selection of at
      risk individuals.

PMID- 24104877
TI  - Ryanodine receptor phosphorylation by oxidized CaMKII contributes to the
      cardiotoxic effects of cardiac glycosides.
AB  - AIMS: Recent studies suggest that proarrhythmic effects of cardiac glycosides
      (CGs) on cardiomyocyte Ca(2+) handling involve generation of reactive oxygen
      species (ROS). However, the specific pathway(s) of ROS production and the
      subsequent downstream molecular events that mediate CG-dependent arrhythmogenesis
      remain to be defined. METHODS AND RESULTS: We examined the effects of digitoxin
      (DGT) on Ca(2+) handling and ROS production in cardiomyocytes using a combination
      of pharmacological approaches and genetic mouse models. Myocytes isolated from
      mice deficient in NADPH oxidase type 2 (NOX2KO) and mice transgenically
      overexpressing mitochondrial superoxide dismutase displayed markedly increased
      tolerance to the proarrhythmic action of DGT as manifested by the inhibition of
      DGT-dependent ROS and spontaneous Ca(2+) waves (SCW). Additionally, DGT-induced
      mitochondrial membrane potential depolarization was abolished in NOX2KO cells.
      DGT-dependent ROS was suppressed by the inhibition of PI3K, PKC, and the
      mitochondrial KATP channel, suggesting roles for these proteins, respectively, in
      activation of NOX2 and in mitochondrial ROS generation. Western blot analysis
      revealed increased levels of oxidized CaMKII in WT but not in NOX2KO hearts
      treated with DGT. The DGT-induced increase in SCW frequency was abolished in
      myocytes isolated from mice in which the Ser 2814 CaMKII phosphorylation site on
      RyR2 is constitutively inactivated. CONCLUSION: These results suggest that the
      arrhythmogenic adverse effects of CGs on Ca(2+) handling involve PI3K- and PKC
      mediated stimulation of NOX2 and subsequent NOX2-dependent ROS release from the
      mitochondria; mitochondria-derived ROS then activate CaMKII with consequent
      phosphorylation of RyR2 at Ser 2814.

PMID- 24104878
TI  - A transgenic mouse model for the simultaneous monitoring of ANF and BNP gene
      activity during heart development and disease.
AB  - AIM: The expression of Nppa (ANF) and Nppb (BNP) marks the chamber myocardium in
      the embryo, and both genes serve as early and accurate markers for hypertrophy
      and heart failure. Non-invasive visualization of Nppa-Nppb expression in living
      mice would enable to evaluate the disease state during the course of time in
      heart disease models. We sought to develop a method to assess the pattern and
      level of Nppa and Nppb expression within living mice. METHODS AND RESULTS: A
      modified bacterial artificial chromosome containing a genomic segment spanning
      the Nppa-Nppb locus was randomly integrated into the mouse genome. Firefly
      Luciferase was inserted into Nppa and the red fluorescent protein gene Katushka
      into Nppb. Both reporters precisely recapitulated the spatio-temporal patterns of
      Nppa and Nppb, respectively. In a hypertrophy model (transverse aortic
      constriction) and myocardial infarction model (left anterior descending coronary
      artery occlusion), the non-invasively measured bioluminescent signal from
      Luciferase correlated with Nppa expression, and the intensity of red fluorescence
      with levels of the expression of Katushka and Nppb. After myocardial infarction,
      the border zone of the infarct area was readily identified by an increased
      intensity of Katushka fluorescence. CONCLUSIONS: A genomic region sufficient to
      regulate the developmental pattern and stress response of Nppa and Nppb has been
      defined. The double reporter mice can be used for the functional imaging and
      investigation of cardiac hypertrophy and myocardial infarction in vivo.

PMID- 24104879
TI  - Role of AMP-activated protein kinase in regulating hypoxic survival and
      proliferation of mesenchymal stem cells.
AB  - AIMS: Mesenchymal stem cells (MSCs) are widely used for cell therapy,
      particularly for the treatment of ischaemic heart disease. Mechanisms underlying
      control of their metabolism and proliferation capacity, critical elements for
      their survival and differentiation, have not been fully characterized. AMP
      activated protein kinase (AMPK) is a key regulator known to metabolically protect
      cardiomyocytes against ischaemic injuries and, more generally, to inhibit cell
      proliferation. We hypothesized that AMPK plays a role in control of MSC
      metabolism and proliferation. METHODS AND RESULTS: MSCs isolated from murine bone
      marrow exclusively expressed the AMPKalpha1 catalytic subunit. In contrast to
      cardiomyocytes, a chronic exposure of MSCs to hypoxia failed to induce cell death
      despite the absence of AMPK activation. This hypoxic tolerance was the
      consequence of a preference of MSC towards glycolytic metabolism independently of
      oxygen availability and AMPK signalling. On the other hand, A-769662, a well
      characterized AMPK activator, was able to induce a robust and sustained AMPK
      activation. We showed that A-769662-induced AMPK activation inhibited MSC
      proliferation. Proliferation was not arrested in MSCs derived from AMPKalpha1
      knockout mice, providing genetic evidence that AMPK is essential for this
      process. Among AMPK downstream targets proposed to regulate cell proliferation,
      we showed that neither the p70 ribosomal S6 protein kinase/eukaryotic elongation
      factor 2-dependent protein synthesis pathway nor p21 was involved, whereas p27
      expression was increased by A-769662. Silencing p27 expression partially
      prevented the A-769662-dependent inhibition of MSC proliferation. CONCLUSION:
      MSCs resist hypoxia independently of AMPK whereas chronic AMPK activation
      inhibits MSC proliferation, p27 being involved in this regulation.

PMID- 24104880
TI  - Identification of two novel BRCA1-partner genes in the DNA double-strand break
      repair pathway.
AB  - M1775R and A1789T are two missense variants located within the BRCT domains of
      BRCA1 gene. The M1775R is a known deleterious variant, while the A1789T is an
      unclassified variant that has been analyzed and classified as probably
      deleterious for the first time by our group. In a previous study, we described
      the expression profile of HeLa G1 cells transfected with the two variants and we
      found that they altered molecular mechanisms critical for cell proliferation and
      genome integrity. Considering that the mutations in the BRCA1 C terminus (BRCT)
      domains are associated to a phenotype with an altered ability in the DNA double
      strand break repair, we chose three of the genes previously identified, EEF1E1,
      MRE11A, and OBFC2B, to be tested for an homologous recombination (HR) in vitro
      assay. For our purpose, we performed a gene expression knockdown by siRNA
      transfection in HeLa cells, containing an integrated recombination substrate
      (hprtDRGFP), for each of the target genes included BRCA1. The knockdown of BRCA1,
      OBFC2B, MRE11A, and EEF1E1 reduces the HR rate, respectively, of 97.6, 28.6,
      41.8, and 42.3 % compared to cells transfected with a scrambled negative control
      duplex and all these differences are statistically significant (P < 0.05; Kruskal
      Wallis test). Finally, we analyzed the effect of target gene depletion both on HR
      that on cell survival after DNA-damage induction by ionizing radiation. The
      clonogenic assay showed that the down-regulation of the target genes reduced the
      cell survival, but the effect on the HR, is not evident. Only the BRCA1-siRNA
      confirmed the inhibition effect on HR. Overall these results confirmed the
      involvement of MRE11A in the HR pathway and identified two new genes, OBFC2B and
      EEF1E1, which according to these data and the knowledge obtained from literature,
      might be involved in BRCA1-pathway. 

PMID- 24104881
TI  - Prognosis of metastatic breast cancer subtypes: the hormone receptor/HER2
      positive subtype is associated with the most favorable outcome.
AB  - Contrary to the situation in early breast cancer, little is known about the
      prognostic relevance of the hormone receptor (HR) and human epidermal growth
      factor receptor 2 (HER2) in metastatic breast cancer. The objectives of this
      study were to present survival estimates and to determine the prognostic impact
      of breast cancer subtypes based on HR and HER2 status in a recent cohort of
      metastatic breast cancer patients, which is representative of current clinical
      practice. Patients diagnosed with metastatic breast cancer between 2007 and 2009
      were included. Information regarding patient and tumor characteristics and
      treatment was collected. Patients were categorized in four subtypes based on the
      HR and HER2 status of the primary tumor: HR positive (+)/HER2 negative (-),
      HR+/HER2+, HR-/HER2+ and triple negative (TN). Survival was estimated using the
      Kaplan-Meier method. Cox proportional hazards model was used to determine the
      prognostic impact of breast cancer subtype, adjusted for possible confounders.
      Median follow-up was 21.8 months for the 815 metastatic breast cancer patients
      included; 66 % of patients had the HR+/HER2- subtype, 8 % the HR-/HER2+ subtype,
      15 % the TN subtype and 11 % the HR+/HER2+ subtype. The longest survival was
      observed for the HR+/HER2+ subtype (median 34.4 months), compared to 24.8 months
      for the HR+/HER2- subtype, 19.8 months for the HR-/HER2+ subtype and 8.8 months
      for the TN subtype (P < 0.0001). In the multivariate analysis, subtype was an
      independent prognostic factor, as were initial site of metastases and metastatic
      free interval. The HR+/HER2+ subtype was associated with the longest survival
      after diagnosis of distant metastases. 

PMID- 24104883
TI  - Blood levels of vitamin D and early stage breast cancer prognosis: a systematic
      review and meta-analysis.
AB  - Vitamin D regulates expression of genes important in development and progression
      of breast cancer. The association of vitamin D with breast cancer outcomes among
      breast cancer patients is controversial. We conducted a systematic review and
      meta-analysis of this association in early stage breast cancer outcome. We
      searched MEDLINE (1982-May 1, 2013), the American Society of Clinical Oncology
      (2009-2012), and the San Antonio Breast Cancer Symposium (2010-2012) for
      abstracts, using the following keywords: "breast cancer" and "prognosis" or
      "survival", and "vitamin D" or" calcitriol" to identify studies reporting the
      associations of blood vitamin D levels (drawn close to diagnosis) with breast
      cancer outcomes. Meta-analyses were performed using an inverse-variance weighted
      fixed-effects model with Stata Version 12. Eight studies including 5,691 patients
      were identified. Vitamin D deficiency was variably categorized across studies; a
      median of 36.8 % of patients were classified as deficient. Low vitamin D levels
      were associated with a pooled hazard ratio of 2.13 (95 % CI 1.64-2.78) and 1.76
      (95 % CIs 1.35-2.30) for recurrence (six studies) and death (four studies),
      respectively, with no evidence of significant heterogeneity across studies. There
      was potential evidence of a publication bias in studies examining associations
      with death (but not in those examining associations with recurrence). These
      findings support an association of low levels of vitamin D with increased risk of
      recurrence and death in early stage breast cancer patients. Given the
      observational nature of the included studies, it cannot be concluded that this
      association is causal. Further research is warranted to investigate the potential
      beneficial effects of vitamin D in breast cancer. 

PMID- 24104882
TI  - Multivitamin and mineral use and breast cancer mortality in older women with
      invasive breast cancer in the women's health initiative.
AB  - Multivitamin use is common in the United States. It is not known whether
      multivitamins with minerals supplements (MVM) used by women already diagnosed
      with invasive breast cancer would affect their breast cancer mortality risk. To
      determine prospectively the effects of MVM use on breast cancer mortality in
      postmenopausal women diagnosed with invasive breast cancer, a prospective cohort
      study was conducted of 7,728 women aged 50-79 at enrollment in the women's health
      initiative (WHI) in 40 clinical sites across the United States diagnosed with
      incident invasive breast cancer during WHI and followed for a mean of 7.1 years
      after breast cancer diagnosis. Use of MVM supplements was assessed at WHI
      baseline visit and at visit closest to breast cancer diagnosis, obtained from
      vitamin pill bottles brought to clinic visit. Outcome was breast cancer
      mortality. Hazard ratios and 95 % confidence intervals (CIs) for breast cancer
      mortality comparing MVM users to non-users were estimated using Cox proportional
      hazard regression models. Analyses using propensity to take MVM were done to
      adjust for potential differences in characteristics of MVM users versus non
      users. At baseline, 37.8 % of women reported MVM use. After mean post-diagnosis
      follow-up of 7.1 +/- 4.1 (SD) years, there were 518 (6.7 %) deaths from breast
      cancer. In adjusted analyses, breast cancer mortality was 30 % lower in MVM users
      as compared to non-users (HR = 0.70; 95 % CI 0.55, 0.91). This association was
      highly robust and persisted after multiple adjustments for potential confounding
      variables and in propensity score matched analysis (HR = 0.76; 95 % CI 0.60
      0.96). Postmenopausal women with invasive breast cancer using MVM had lower
      breast cancer mortality than non-users. The results suggest a possible role for
      daily MVM use in attenuating breast cancer mortality in women with invasive
      breast cancer but the findings require confirmation. 

PMID- 24104884
TI  - Response to Primack's comment: Mother's milk.

PMID- 24104885
TI  - New therapeutic avenues in ulcerative colitis: thinking out of the box.
AB  - Ulcerative colitis (UC) is a chronic idiopathic inflammatory disease of the
      gastrointestinal tract that affects the mucosal lining of the colon. Recent
      epidemiological data show that its incidence and prevalence are increasing in
      many parts of the world, in parallel with altered lifestyles, improved access to
      health, improved sanitation and industrialisation rates. Current therapeutic
      strategies for treating UC have only been moderately successful. Despite major
      recent advances in inflammatory bowel disease therapeutic resources, a
      considerable proportion of patients are still refractory to conventional
      treatment. Less than half of all patients achieve long-term remission, many
      require colectomy, and the disease still has a major impact on patients' lives.
      Moreover, recent data point to slightly raised mortality. While these outcomes
      could be partly improved by optimising current therapeutic strategies, they
      clearly highlight the need to develop new therapies. Currently, a number of
      promising and innovative therapeutic approaches are being explored, some of which
      will hopefully survive to reach the clinic. Until such a time arrives, it is
      important that a better understanding of the clinical particularities of the
      disease, an improved knowledge of the host-microbiome negative interactions and
      of the environmental factors beyond disease development is achieved to obtain the
      final and desired outcome: to provide better treatment and quality of life for
      patients with this disabling disease. 

PMID- 24104886
TI  - Recent advances in inflammatory bowel disease: mucosal immune cells in intestinal
      inflammation.
AB  - The intestine and its immune system have evolved to meet the extraordinary task
      of maintaining tolerance to the largest, most complex and diverse microbial
      commensal habitat, while meticulously attacking and containing even minute
      numbers of occasionally incoming pathogens. While our understanding is still far
      from complete, recent studies have provided exciting novel insights into the
      complex interplay of the many distinct intestinal immune cell types as well as
      the discovery of entirely new cell subsets. These studies have also revealed how
      proper development and function of the intestinal immune system is dependent on
      its specific microbiota, which appears to have evolutionarily co-evolved. Here we
      review key immune cells that maintain intestinal homeostasis and, conversely,
      describe how altered function and imbalances may lead to inflammatory bowel
      disease (IBD). We highlight the latest developments within this field, covering
      the major players in IBD including intestinal epithelial cells, macrophages,
      dendritic cells, adaptive immune cells, and the newly discovered innate lymphoid
      cells, which appear of characteristic importance for immune function at mucosal
      surfaces. We set these mucosal immune pathways in the functional context of IBD
      risk genes where such insight is available. Moreover, we frame our discussion of
      fundamental biological pathways that have been elucidated in model systems in the
      context of results from clinical trials in IBD that targeted key mediators
      secreted by these cells, as an attempt of 'functional' appraisal of these
      pathways in human disease. 

PMID- 24104887
TI  - Red but not white meat consumption is associated with metabolic syndrome, insulin
      resistance and lipid peroxidation in Brazilian middle-aged men.
AB  - BACKGROUND: The influence of diet on metabolic syndrome and oxidative stress are
      not completely known. DESIGN: This cross-sectional study assessed the association
      of red meat and white meat consumption with metabolic syndrome, insulin
      resistance and lipid peroxidation in Brazilian middle-aged men. METHODS: A total
      of 296 subjects (age: 50.5 +/- 5.0 years, body mass index: 25.8 +/- 3.5 kg/m(2))
      were evaluated. Anthropometry, lifestyle features, blood biochemical parameters,
      diagnosis of metabolic syndrome, homeostatic model assessment for insulin
      resistance, a lipid peroxidation marker (oxidized low-density lipoprotein) and
      triglycerides:high-density lipoprotein cholesterol ratio were assessed. Dietary
      intake was estimated by a food frequency questionnaire. RESULTS: The subjects
      included in the highest tertile red meat (>=81.5 g/d) and saturated fatty acid
      from red meat consumption (>=4.3 g/d) had higher occurrence of central obesity
      (nearly 60%, p < 0.01), hypertriglyceridaemia (nearly 43%, p < 0.01) and
      metabolic syndrome (35%, p < 0.01). They also had higher values of homeostatic
      model assessment for insulin resistance, oxidized low-density lipoprotein, and
      triglycerides:high-density lipoprotein cholesterol ratio, regardless of
      interfering factors. There were no associations of highest white meat tertile
      (>=39.4 g/d) and saturated fatty acid from white meat (>=1.0 g/d) consumption
      with the assessed parameters (p > 0.05). CONCLUSIONS: Red meat consumption was
      cross-sectionally associated with the occurrence of central obesity,
      hypertriglyceridaemia, and metabolic syndrome as well as with higher homeostatic
      model assessment for insulin resistance, oxidized low-density lipoprotein
      concentrations and triglycerides:high-density lipoprotein cholesterol ratio. The
      content of saturated fatty acid from red meat consumption may be a factor that
      contributed to this relationship, while white meat consumption was not associated
      with metabolic syndrome and the assessed biomarkers.

PMID- 24104889
TI  - Disturbed adiponectin - AMPK system in skeletal muscle of patients with metabolic
      syndrome.
AB  - Patients with metabolic syndrome are characterized by low circulating adiponectin
      levels and reduced adiponectin sensitivity in skeletal muscles. Through binding
      on its main skeletal muscle receptor AdipoR1, adiponectin activates AMP-activated
      protein kinase (AMPK), a key player in energy homeostasis. Fourteen metabolic
      syndrome patients and seven healthy control subjects were included. Blood samples
      were taken to determine insulin resistance, adiponectin, lipoproteins, and C
      reactive protein. Muscle biopsies (m. vastus lateralis) were obtained to assess
      mRNA expression of AdipoR1 and both AMPKalpha1 and AMPKalpha2 subunits, as well
      as downstream targets in lipid and glucose metabolism. Skeletal muscle mRNA
      expression of AMPKalpha1 and AMPKalpha2 was lower in metabolic syndrome patients
      (100 +/- 6 vs. 122 +/- 8 AU, p = 0.030 and 64 +/- 4 vs. 85 +/- 9 AU, p = 0.044,
      respectively), whereas the expression of AdipoR1 was upregulated (138 +/- 9 vs.
      105 +/- 7, p = 0.012). AMPKalpha1 and AdipoR1 correlated positively in both the
      control (r = 0.964, p < 0.001) and the metabolic syndrome group (r = 0.600, p =
      0.023). However, this relation was shifted upwards in metabolic syndrome
      patients, indicating increased AdipoR1mRNA expression for a similar AMPKalpha1
      expression. Previously, a blunted stimulatory effect of adiponectin on AMPK
      activation has been shown in metabolic syndrome patients. The present data
      suggest that the disturbed interaction of adiponectin with AMPK is located
      downstream of the AdipoR1 receptor.

PMID- 24104888
TI  - Role of electrocardiography and echocardiography in prevention and predicting
      outcome of subjects at increased risk of heart failure.
AB  - BACKGROUND: Asymptomatic left ventricular dysfunction (ALVD) is relatively common
      in both community and high-risk populations. Early pharmacological intervention
      can improve clinical outcomes in subjects with this condition. OBJECTIVES: This
      multicentre study consists on electrocardiographic and echocardiographic
      examination of stage A and B heart failure (HF) asymptomatic subjects with one or
      more cardiovascular risk factors, to assess the prognostic value of
      cardiovascular risk factors per se, clinical history, and electrocardiographic
      and echocardiographic parameters in prediction of progression of HF and/or in
      development of cardiovascular primary or secondary events. MATERIAL AND METHODS:
      A total of 2142 asymptomatic subjects (mean age 63 years, 1162 males) performed
      an electrocardiographic and echocardiographic examination. Electrocardiogram
      (ECG) pathological signs according to Minnesota code and left ventricular
      dysfunction both systolic and diastolic by echocardiography were evaluated. There
      were 2002 subjects who were followed up for 26 +/- 11 months, observing their
      primary and secondary end points. RESULTS: At follow up, the study population
      presented 111 primary end points (5.2%) and 441 secondary end points (20.6%). ECG
      criteria of LV hypertrophy and signs of ischaemia or previous myocardial
      infarction (p < 0.0001) were highly significantly related to primary end points.
      Both ECG and echocardiography (systolic function) are able at Kaplan-Meier
      cumulative survival curves to predict primary end points (p < 0.0001).
      CONCLUSIONS: Presence or absence of left ventricular systolic and /or diastolic
      dysfunction has an incremental value in comparison to cardiovascular risk
      factors, clinical history, and ECG findings to predict both the evolution towards
      a more severe HF stage (stage C) and also the occurrence of cardiovascular
      events.

PMID- 24104924
TI  - A substantial prehistoric European ancestry amongst Ashkenazi maternal lineages.
AB  - The origins of Ashkenazi Jews remain highly controversial. Like Judaism,
      mitochondrial DNA is passed along the maternal line. Its variation in the
      Ashkenazim is highly distinctive, with four major and numerous minor founders.
      However, due to their rarity in the general population, these founders have been
      difficult to trace to a source. Here we show that all four major founders, ~40%
      of Ashkenazi mtDNA variation, have ancestry in prehistoric Europe, rather than
      the Near East or Caucasus. Furthermore, most of the remaining minor founders
      share a similar deep European ancestry. Thus the great majority of Ashkenazi
      maternal lineages were not brought from the Levant, as commonly supposed, nor
      recruited in the Caucasus, as sometimes suggested, but assimilated within Europe.
      These results point to a significant role for the conversion of women in the
      formation of Ashkenazi communities, and provide the foundation for a detailed
      reconstruction of Ashkenazi genealogical history. 

PMID- 24104926
TI  - "The stems of future corneal research development are already in our hands" 18th
      annual meeting of the Kyoto Cornea Club, December 7-8, 2012.

PMID- 24104925
TI  - Improvement of sequence selectivity in triple helical recognition of RNA by
      phenylalanine-derived PNA.
AB  - Modified peptide nucleic acids (PNA) containing one or two thymine PNA monomers
      derived from phenylalanine were synthesized. Triple helix formation by these
      modified PNAs with RNA and DNA hairpins having a variable base pair in the middle
      of the helix were studied using isothermal titration calorimetry and compared
      with triple helix formation by non-modified PNAs. While unmodified PNA had low
      sequence selectivity against mismatched hairpins, introduction of one or two
      phenylalanine-derived monomers significantly increased the mismatch
      discrimination and sequence selectivity of the modified PNA. Consistent with our
      previous observations, PNA formed more stable triple helices with RNA than with
      DNA. Interestingly, the phenylalanine modification further improved the
      preference of PNA for RNA over DNA hairpin. 

PMID- 24104927
TI  - Development and prospects of organ replacement regenerative therapy.
AB  - Current approaches for the development of regenerative therapies have been
      influenced by our understanding of embryonic development, stem cell biology, and
      tissue engineering technology. The ultimate goal of regenerative therapy is to
      develop fully functioning bioengineered organs to replace lost or damaged organs
      that result from disease, injury, or aging. Almost all organs including
      ectodermal organs, such as teeth, hair, salivary glands, and lacrimal glands,
      arise from organ germs induced by reciprocal epithelial-mesenchymal interactions
      in the developing embryo. A novel concept to generate a bioengineered organ is to
      recreate organogenesis and thereby develop fully functioning bioengineered organs
      from the resulting bioengineered organ germ generated via 3-dimensional cell
      manipulation using immature stem cells in vitro. We have previously developed a
      bioengineering method for forming a 3-dimensional organ germ in the early
      developmental stages, termed the "bioengineered organ germ method." Recently, we
      reported fully functioning bioengineered tooth replacements after transplantation
      of a bioengineered tooth germ or a mature tooth unit comprising the bioengineered
      tooth and periodontal tissues. This concept could be adopted to generate not only
      teeth but also bioengineered hair follicles, salivary glands, and lacrimal
      glands. These studies emphasize the potential for bioengineered organ replacement
      in future regenerative therapies. In this review, we will summarize the
      strategies and the recent progress of research and development for the
      establishment of organ replacement regenerative therapies.

PMID- 24104928
TI  - Us3, a multifunctional protein kinase encoded by herpes simplex virus 1: how does
      it function in vivo?
AB  - Phosphorylation is a common protein modification by which a cell or virus
      regulates protein activity, and subsequently cellular and viral functions.
      Herpesviruses commonly encode protein kinases that regulate their own replicative
      processes and modify host cellular machinery, by phosphorylating target proteins.
      Although numerous studies have revealed the multiple downstream effects of viral
      protein kinases and their potential molecular mechanisms, it remains unknown
      whether herpes viral protein kinases are involved in viral replication and
      pathogenicity in vivo. This review focuses on Us3 protein kinase encoded by
      herpes simplex virus 1 and provides a current overview of its functions in
      infected cells, with a special focus on their relevancy in vivo.

PMID- 24104929
TI  - Evolution of endothelial keratoplasty.
AB  - Endothelial keratoplasty has evolved into a popular alternative to penetrating
      keratoplasty (PK) for the treatment of endothelial dysfunction. Although the
      earliest iterations were challenging and were not widely adopted, the iteration
      known as Descemet stripping endothelial keratoplasty (DSEK) has gained widespread
      acceptance. DSEK combines a simplified technique for stripping dysfunctional
      endothelium from the host cornea and microkeratome dissection of the donor
      tissue, a step now commonly completed in advance by eye bank technicians. Studies
      show that a newer endothelial keratoplasty iteration, known as Descemet membrane
      endothelial keratoplasty (DMEK), provides an even faster and better visual
      recovery than DSEK does. In addition, DMEK significantly reduces the risk of
      immunologic graft rejection episodes compared with that in DSEK or in PK.
      Although the DMEK donor tissue, consisting of the bare endothelium and Descemet
      membrane without any stroma, is more challenging to prepare and position in the
      recipient eye, recent improvements in instrumentation and surgical techniques are
      increasing the ease and the reliability of the procedure. DSEK successfully
      mitigates 2 of the main liabilities of PK: ocular surface complications and
      structural problems (including induced astigmatism and perpetually weak wounds),
      whereas DMEK further mitigates the 2 principal remaining liabilities of PK:
      immunologic graft reactions and secondary glaucoma from prolonged topical
      corticosteroid use.

PMID- 24104930
TI  - Who pays the toll for solving the enigma of corneal herpes?
AB  - In herpetic stromal keratitis (HSK), herpes simplex virus type-1 DNA fragments
      and herpes simplex virus-immunoglobulin G immune complexes are present in corneas
      long after the infective virus has disappeared. These viral components are highly
      immunogenic and potentiate the production of proinflammatory cytokines and
      chemokines via Toll-like receptors expressed on corneal cells and macrophages. In
      addition, angiogenic factors, such as the vascular endothelium growth factor and
      the tissue-damaging enzyme, matrix metalloproteinase 9, are induced by corneal
      cells and macrophages through the recognition of these viral components in the
      pathogenesis of HSK. Upon neovascularization, robust infiltration of leukocytes
      via leaky new vessels is elicited. Activated polymorphonuclear leukocytes (PMNs)
      secrete hydrogen peroxide and myeloperoxidase, which inhibit viral growth. PMNs
      also produce tumor necrosis factor, monokine-induced by interferon-gamma (CXCL9),
      and nitric oxide. These factors provide a local environment that can induce the
      differentiation of peripheral CD4* T cells to induce Th1-predominant
      immunopathology. Thus, strategies developed to alter these pathways should lead
      to new preventative and therapeutic measures for the treatment of HSK.

PMID- 24104931
TI  - Microsporidia infection of the cornea--a unique and challenging disease.
AB  - Microsporidia are a diverse group of obligate, intracellular, eukaryotic, spore
      forming parasites. Traditionally, these were considered as protozoans but
      recently have been reclassified as fungi. Microsporidia behave as opportunistic
      pathogens causing systemic infections. In the eye, Microsporidia cause
      keratoconjunctivitis, corneal stromal keratitis, scleritis, and endophthalmitis.
      This review shares our experiences with anterior segment infections caused by
      this pathogen. Keratoconjunctivitis is a common form of ocular infection caused
      by the parasite. Although early reports described it as occurring only in
      immunosuppressed individuals, it can also occur in immunocompetent individuals.
      The disease shows a seasonal pattern with a peak incidence during the rainy
      season. Although several drugs have been considered, our experience suggests that
      keratoconjunctivitis is a self-limiting disease. In contrast to
      keratoconjunctivitis, stromal keratitis is an ill-defined disease. We collected
      30 cases and analyzed the various aspects of this disease. Stromal keratitis is
      characterized by a slowly progressive course. The corneal picture resembles
      herpes simplex virus stromal keratitis or fungal keratitis cases, and is
      characterized by deep stromal infiltrates with overlying and surrounding stromal
      edema and keratic precipitates. The diagnosis of Microsporidia infection is
      confirmed by a microscopic examination of smears from patients with ulcerative
      keratitis or by a histopathological examination of corneal tissues. Definitive
      genus identification requires the examination of specimens by electron microscopy
      or by molecular methods. In the absence of a definitive medical treatment, nearly
      all patients require surgical treatment. The confusion regarding Microsporidia is
      not only limited to their classification but also extends to various aspects of
      the corneal disease caused by them.

PMID- 24104932
TI  - Multidrug-resistant bacteria induce recurrent keratoconjunctivitis in a patient
      with common variable immunodeficiency: case report and literature review.
AB  - PURPOSE: We present a case study regarding a patient with recurrent
      keratoconjunctivitis that presented as an initial manifestation of common
      variable immunodeficiency (CVID). METHODS: We describe a case and review the
      recent relevant medical literature. RESULTS: A 33-year-old male had recurrent
      keratoconjunctivitis induced by multidrug-resistant bacteria. Topical vancomycin
      treatment was effective, but infection recurred when the vancomycin treatment was
      stopped. The patient was transferred to the Department of Medicine to rule out
      potential systemic immune diseases and was finally diagnosed with CVID.
      Intravenous immunoglobulin (IVIG) was administered, and the patient was followed
      up monthly without any recurrence of infection to date. IVIG will be administered
      monthly for the patient's lifetime. CONCLUSIONS: Keratoconjunctivitis is a CVID
      associated manifestation, sometimes appearing as the first presentation. CVID
      should be considered when unexplained recurrent conjunctival and/or corneal
      bacterial infections are observed. Topical therapy is not sufficient to treat
      this infection and IVIG is necessary.

PMID- 24104933
TI  - The role of extracellular matrix in corneal wound healing.
AB  - During wound healing, cell migration, proliferation, differentiation, and
      enhanced biosynthetic activities are observed at the sites of injury.
      Interactions between extracellular matrix (ECM) components and specific cell
      surface receptors, such as integrins, initiate cascades of signal transduction
      leading to various cellular responses. This review will focus on the biological
      functions of several ECM components, such as osteopontin (OPN), tenascin (TCN),
      and lumican (Lum). The loss of OPN or TCN reduces macrophage invasion and
      myofibroblast differentiation in the healing stroma and is associated with the
      suppression of fibrogenic gene expression in response to injury sustained in
      mice. Gene expression analysis showed that the lack of OPN or TCN resulted in the
      inhibition of proinflammatory and fibrogenic gene expression. It has been shown
      that Lum also modulates cell adhesion, migration, and proliferation, thus
      contributing to corneal epithelial wound healing. Interestingly, OPN-, TCN-, or
      Lum-null mice had reduced Smad activity and epithelial-mesenchymal transitions.
      Smads are nuclear effectors of transforming growth factor-beta and regulate
      transcription. However, it is still not clear as to how individual ECM components
      initiate the signaling pathway. We hypothesized that a cell surface receptor for
      these ECM components may mediate the matrikine functions of Lum. To identify the
      specific receptor for Lum, we developed purified recombinant glutathione S
      transferase-Lum. Using this, we identified a potential receptor for Lum that
      modulated wound healing.

PMID- 24104934
TI  - Effect of subconjunctival lacrimal gland transplantation in a rabbit dry eye
      model.
AB  - PURPOSE: The main and accessory lacrimal glands are involved in reflex and basal
      secretion of tears, respectively, with the glandular tissue anatomy being similar
      for both glands. We transplanted part of the main lacrimal gland under the
      palpebral conjunctiva in a rabbit dry eye model and assessed the therapeutic
      effect of this procedure. METHODS: In New Zealand White rabbits, the greater
      superficial petrosal nerve was cut unilaterally under a microscope. The other eye
      served as a normal control. For transplantation, approximately 0.07 g of the main
      lacrimal gland was harvested from the normal side, labeled with
      octadecylindocarbocyanine, and transplanted under the palpebral conjunctivae of
      both eyes. At 1 week and 1 month after the transplantation, the eyes were
      observed, and the Schirmer tear test and histological examination of the
      palpebral conjunctiva were performed. RESULTS: On the denervated side, tear flow,
      measured by the Schirmer tear test, recovered at 1 month after the
      transplantation of the main lacrimal gland compared with that before
      transplantation. The contralateral control side showed no changes. On the
      denervated side, the fluorescein score significantly improved at 1 month after
      transplantation compared with that before transplantation (P < 0.005), whereas
      the rose bengal score showed no difference. Histological examination revealed
      that octadecylindocarbocyanine-labeled transplanted main lacrimal gland tissue
      was present under the palpebral conjunctiva. CONCLUSIONS: These results suggest
      that the partial transplantation of the main lacrimal gland may be effective for
      treatment of dry eyes.

PMID- 24104935
TI  - Development of automated conjunctival hyperemia analysis software.
AB  - Conjunctival hyperemia is observed in a variety of ocular inflammatory
      conditions. The evaluation of hyperemia is indispensable for the treatment of
      patients with ocular inflammation. However, the major methods currently available
      for evaluation are based on nonquantitative and subjective methods. Therefore, we
      developed novel software to evaluate bulbar hyperemia quantitatively and
      objectively. First, we investigated whether the histamine-induced hyperemia of
      guinea pigs could be quantified by image analysis. Bulbar conjunctival images
      were taken by means of a digital camera, followed by the binarization of the
      images and the selection of regions of interest (ROIs) for evaluation. The ROIs
      were evaluated by counting the number of absolute pixel values. Pixel values
      peaked significantly 1 minute after histamine challenge was performed and were
      still increased after 5 minutes. Second, we applied the same method to antigen
      (ovalbumin)-induced hyperemia of sensitized guinea pigs, acquiring similar
      results except for the substantial upregulation in the first 5 minutes after
      challenge. Finally, we analyzed human bulbar hyperemia using the new software we
      developed especially for human usage. The new software allows the automatic
      calculation of pixel values once the ROIs have been selected. In our clinical
      trials, the percentage of blood vessel coverage of ROIs was significantly higher
      in the images of hyperemia caused by allergic conjunctival diseases and hyperemia
      induced by Bimatoprost, compared with those of healthy volunteers. We propose
      that this newly developed automated hyperemia analysis software will be an
      objective clinical tool for the evaluation of ocular hyperemia.

PMID- 24104936
TI  - Keratoplasty postoperative treatment update.
AB  - Immunosuppressive therapy is the main postoperative treatment for keratoplasty,
      but there are considerable differences in protocols for the use of steroids and
      other immunosuppressants. Therefore, we conducted 2 prospective randomized
      clinical trials and 1 prospective nonrandomized clinical trial on keratoplasty
      postoperative treatment. One study evaluated the efficacy and safety of long-term
      topical corticosteroids after a penetrating keratoplasty was performed. Patients
      who underwent keratoplasty and maintained graft clarity for >1 year were randomly
      assigned to either a steroid or a no-steroid group. At the 12-month follow-up,
      the no-steroid group developed significantly more endothelial rejection than did
      the steroid group. A second study elucidated the effectiveness and safety of
      systemic cyclosporine in high-risk corneal transplantation. The patients were
      assigned to a systemic cyclosporine or control group. At a mean follow-up of 42.7
      months, no difference was observed in the endothelial rejection rates and graft
      clarity loss between the 2 groups. A third study elucidated the effectiveness and
      the safety of systemic tacrolimus in high-risk corneal transplantation. Of 11
      consecutive eyes decompensated despite systemic cyclosporine treatment, there was
      no irreversible rejection in eyes treated with tacrolimus, which was
      significantly better than in previous penetrating keratoplasty with systemic
      cyclosporine treatment. Prognosis after keratoplasty in patients with keratoconus
      is relatively good, but special attention is required for patients with atopic
      dermatitis. Postkeratoplasty atopic sclerokeratitis (PKAS) is a severe form of
      sclerokeratitis after keratoplasty in atopic patients. Our retrospective study
      showed that 35 eyes of 29 patients from a total of 247 keratoconus eyes
      undergoing keratoplasty were associated with atopic dermatitis, of which 6 eyes
      of 5 patients developed PKAS. Eyes with PKAS had a significantly higher incidence
      of atopic blepharitis and preoperative corneal neovascularization, and therefore,
      we suggest systemic corticosteroids or cyclosporine to prevent PKAS in such high
      risk cases.

PMID- 24104937
TI  - Validity of noninvasive meibography systems: noncontact meibography equipped with
      a slit-lamp and a mobile pen-shaped meibograph.
AB  - Meibomian glands (MGs) secrete lipids (meibum) into the tear film and prevent
      excessive evaporation. MG dysfunction (MGD) is a major cause of evaporative dry
      eye. Recent studies have demonstrated that evaporative dry eye resulting from MGD
      is far more common than aqueous-deficient dry eye is. Meibography is the only
      technique that can be used to observe the structure of MGs in silhouette, by
      illuminating the eyelids from the skin side, and can detect the morphological
      abnormalities in MGs. However, conventional meibography uses a transilluminating
      light probe directly applied onto the eyelid and thus is invasive. To assess this
      problem, we developed 2 noninvasive meibography systems (a slit-lamp type and
      mobile type). In this review, various clinical applications of noninvasive
      meibography systems are demonstrated. Changes in MGs were examined in contact
      lens wearers or in patients with allergic conjunctivitis, MGD, aqueous-deficient
      dry eye, or long-term antiglaucoma eye drop use. The use of a noninvasive
      meibography system could detect morphological changes such as dropout,
      shortening, dilation, and distortion of MGs in patients. The ability to detect
      detailed changes of MGs using noninvasive meibography enhances the power to
      diagnose MGD and correctly decide the most effective treatment for patients with
      MGD.

PMID- 24104938
TI  - Utility of real-time PCR analysis for appropriate diagnosis for keratitis.
AB  - Real-time polymerase chain reaction (PCR) is a quantitative method to measure the
      amount of amplified PCR product in real time with high sensitivity. We have
      applied this method to detect pathogens in cases of keratitis with an unknown
      cause. The scraped corneal epithelium for epithelial keratitis or aqueous humor
      for stromal or endothelial keratitis was obtained and DNA was extracted. The DNA
      from specific pathogens was amplified using specific primers and TaqMan probe,
      and assessed quantitatively. Here, we review previously reported noteworthy
      examples of keratitis diagnosed by our real-time PCR system as follows: cases
      with Acanthamoeba keratitis whose causative pathogen was only detected by real
      time PCR despite not being detected by histological examination and culture;
      zoster sine herpete with atypical pseudodendrite; acyclovir-resistant herpetic
      keratitis estimated by changes in viral DNA copy numbers before and after
      treatment; and corneal endotheliitis positive for cytomegalovirus, human herpes
      virus-7, or human herpes virus-8. Real-time PCR helps ophthalmologists to make an
      early diagnosis and provide appropriate treatment for keratitis with complex
      clinical appearances.

PMID- 24104939
TI  - Bullous keratopathy as a progressive disease: evidence from clinical and
      laboratory imaging studies.
AB  - Bullous keratopathy is categorized as a corneal endothelial disease. However,
      pathological changes, including subepithelial fibrosis and the accumulation of
      extracellular matrix, have been detected in the corneal stroma of individuals
      with this condition. In vivo confocal microscopy allows the visualization of
      human corneal cellular structures and has provided information regarding how eyes
      are affected by various diseases. However, the determination of disease
      pathogenesis on the basis of in vivo confocal microscopic observations is
      problematic. We evaluated the structural alterations in the corneal stroma of
      eyes affected by bullous keratopathy using second harmonic generation microscopy
      and laser confocal immunofluorescence microscopy of whole-mount preparations.
      Using these approaches, we detected the transdifferentiation of keratocytes into
      fibroblasts and myofibroblasts at the anterior and posterior stroma and the
      presence of subepithelial fibrosis at the anterior stroma and disorganized
      collagen lamellae at the posterior stroma of the bullous keratopathy cornea.
      These changes were only detected in specimens from eyes with stromal edema
      lasting at least 12 months. Similar time-dependent changes were apparent by using
      in vivo confocal microscopy in the corneal stroma of patients with bullous
      keratopathy after performing a Descemet stripping automated endothelial
      keratoplasty surgery and were associated with an unfavorable outcome with regard
      to postoperative visual acuity. Our observations suggest that pathological
      changes in the corneal stroma of patients with bullous keratopathy are
      progressive and affect postoperative visual acuity after a Descemet stripping
      automated endothelial keratoplasty surgery is performed.

PMID- 24104941
TI  - Theoretical determination of spin Hamiltonians with isotropic and anisotropic
      magnetic interactions in transition metal and lanthanide complexes.
AB  - The determination of anisotropic magnetic parameters is a task of both
      experimental and theoretical interest. The added value of theoretical
      calculations can be crucial for analyzing experimental data by (i) allowing
      assessment of the validity of the phenomenological spin Hamiltonians, (ii)
      allowing discussion of the values of parameters extracted from experiments, and
      (iii) proposing rationalizations and magneto-structural correlations to better
      understand the relations between geometry, electronic structure, and properties.
      In this review, we discuss the model Hamiltonians that are used to describe
      magnetic properties, the computational approaches that can be used to compute
      magnetic parameters, and review their applications to transition metal and (to a
      lesser extent) lanthanide based complexes. Perspectives concerning current
      methodological challenges will then be presented, and finally the need for
      further joint experimental/theoretical efforts will be underlined. 

PMID- 24104940
TI  - New findings for an old disease: morphological studies on pseudoexfoliation
      syndrome-related keratopathy and binocular asymmetry.
AB  - PURPOSE: To review our previous studies regarding the morphology of the cornea in
      pseudoexfoliation syndrome (PEX) and anatomical discrepancies between PEX and
      contralateral eyes in unilateral PEX. METHODS: We used in vivo confocal
      microscopy to observe the corneas of PEX, contralateral, and normal control eyes.
      Morphological alterations correlated with the corneal sensitivity of the eyes
      with PEX. Anterior segment optical coherence tomography was used to study
      patients diagnosed with unilateral PEX. Dynamic dark-light changes of the
      anterior chamber angle and iris were captured by anterior segment optical
      coherence tomography real-time video recording. Anterior chamber angle parameters
      and iridolenticular contact distance were analyzed. The result of a national
      survey on the etiology of bullous keratopathy is presented. RESULTS: Corneal cell
      density was decreased in PEX eyes compared with that of normal control eyes. The
      density of the subbasal nerve plexus was significantly decreased but with
      increased tortuosity. Morphological changes correlated with decreased corneal
      sensitivity. Contralateral PEX eyes shared similar morphological changes with PEX
      eyes. Eyes with PEX had a significantly shallower anterior chamber and decreased
      angle openness during light-induced pupil constriction. The iridolenticular
      contact distance was significantly greater in PEX eyes than in contralateral
      eyes. A Japanese national survey demonstrated the increased incidence of PEX
      endotheliopathy as the cause of unknown bullous keratopathy. CONCLUSIONS: PEX
      keratopathy involves all layers of the cornea. Morphological changes of the
      anterior chamber may contribute to PEX progression. Contralateral eyes were at
      preclinical stages of the PEX process. PEX endotheliopathy accounts for an
      increased incidence of bullous keratopathy, especially in a country with a large
      aged population, such as Japan.

PMID- 24104942
TI  - The French initiated FESUM - historical development, experience and perspectives.
AB  - FESUM is an association dedicated to management, research and education of hand
      trauma. Created by surgeons in 1979, it is now accepted by the national and
      regional health administrations. The first goal of FESUM is to apply strict
      guidelines for specialized hand trauma centers. These guidelines are verified on
      site by 2 FESUM surgeons, and re-checked every 3 years. Patients are selected to
      be directed to the FESUM cen-ters following very simple recommendations: every
      severe trauma must be addressed to and accepted by FESUM centers, 24/7. Seemingly
      less severe lesions such as deep palmar lacerations must also be systematically
      explored in FESUM centers to ensure patients have the best opportunity for
      treatment. Prevention is also a very important part of FESUM activities. The
      FESUM prevention campaigns are currently focused more specifically on daily life
      trauma, that represents 2/3 of the total injuries and is very poorly managed by
      authorities. 

PMID- 24104944
TI  - Improvement of functional recovery of donor heart following cold static storage
      with doxycycline cardioplegia.
AB  - Injury to the donor heart during cold preservation has a negative impact on graft
      survival before transplantation. This study aims to examine whether doxycycline,
      known as an MMP-2 inhibitor, has a positive effect on donor heart preservation
      via its antioxidant action when added to standard preservation solution. Hearts
      were obtained from 3-month-old male Wistar rats and randomly divided into three
      groups: hearts stored for 1 h at 4  degrees C (1) with doxycycline preservation
      solution (DOX cardioplegia) with low Ca(2+); (2) with standard cardioplegia with
      low Ca(2+); and (3) unstored hearts. All hearts were perfused in working mode,
      arrested at 37  degrees C, removed from the perfusion system, reattached in
      Langendorff perfusion system, and converted to working mode for 1 h. At the end
      of the storage period, hearts preserved in DOX cardioplegia had significantly
      less weight gain than those preserved in the standard cardioplegia. DOX
      cardioplegia-induced preservation resulted in significantly higher heart rates
      and better recovery quality during reperfusion in aortic flow compared to the
      standard cardioplegia group. Recovery in the left ventricular function and
      Lambeth Convention Arrhythmia scores during 1 h reperfusion were also
      significantly better in the DOX cardioplegia group. Biochemical data showed that
      DOX cardioplegia prevented an increase in MMP-2 activity and blocked apoptosis
      through increased activity of the pro-survival kinase Akt in the donor heart
      homogenates. DOX cardioplegia also led to a balanced oxidant/antioxidant level in
      the heart homogenates. This is the first study to report that cardioplegia
      solution containing doxycycline provides better cardioprotection via the
      preservation of heart function, through its role in controlling cellular redox
      status during static cold storage. 

PMID- 24104943
TI  - Human babesiosis in Europe: what clinicians need to know.
AB  - Although best known as an animal disease, human babesiosis is attracting
      increasing attention as a worldwide emerging zoonosis. Humans are commonly
      infected by the bite of ixodid ticks. Rare ways of transmission are
      transplacental, perinatal and transfusion-associated. Infection of the human host
      can cause a very severe host-mediated pathology including fever, and hemolysis
      leading to anemia, hyperbilirubinuria, hemoglobinuria and possible organ failure.
      In recent years, apparently owing to increased medical awareness and better
      diagnostic methods, the number of reported cases in humans is rising steadily
      worldwide. Hitherto unknown zoonotic Babesia spp. are now being reported from
      geographic areas where babesiosis was not previously known to occur and the
      growing numbers of travelers and immunocompromised individuals suggest that the
      frequency of cases in Europe will also continue to rise. Our review is intended
      to provide clinicians with practical information on the clinical management of
      this rare, but potentially life-threatening zoonotic disease. It covers
      epidemiology, phylogeny, diagnostics and treatment of human babesiosis and the
      potential risk of transfusion-transmitted disease with a special focus on the
      European situation. 

PMID- 24104945
TI  - Kidney function after the intraoperative use of 6% tetrastarches (HES 130/0.4 and
      0.42).
AB  - Concerns about the nephrotoxicity of tetrastarches have recently increased with
      the accumulation of new evidence, particularly in relationship to septic
      patients. Two meta-analyses in 2011 and early 2012 also raised concerns about
      nephrotoxicity in surgical patients and prompted the present review of the
      nephrotoxicity of tetrastarches solely in the surgical setting. Seven reports
      consisting of two review articles and five single-trial papers published between
      2012 and August 2013 were examined. Six of the seven studies did not show any
      adverse renal outcomes following the intraoperative use of tetrastarch, although
      their data are not robust enough to confirm definitive safety. Moreover, balanced
      electrolyte solutions are strongly recommended as a carrier solution for
      tetrastarches to reduce adverse outcomes. 

PMID- 24104946
TI  - Autoimmune limbic encephalitis and anesthesia.

PMID- 24104947
TI  - Reassessing manual proportions in Australopithecus afarensis.
AB  - Previous analyses of hand morphology in Australopithecus afarensis have concluded
      that this taxon had modern human-like manual proportions, with relatively long
      thumbs and short fingers. These conclusions are based on the A.L.333 composite
      fossil assemblage from Hadar, Ethiopia, and are premised on the ability to assign
      phalanges to a single individual, and to the correct side and digit. Neither
      assignment is secure, however, given the taphonomy and sample composition at
      A.L.333. We use a resampling approach that includes the entire assemblage of
      complete hand elements at Hadar, and takes into account uncertainties in
      identifying phalanges by individual, side and digit number. This approach
      provides the most conservative estimates of manual proportions in Au. afarensis.
      We resampled hand long bone lengths in Au. afarensis and extant hominoids, and
      obtained confidence limits for distributions of manual proportions in the latter.
      Results confirm that intrinsic manual proportions in Au. afarensis are dissimilar
      to Pan and Pongo. However, manual proportions in Au. afarensis often fall at the
      upper end of the distribution in Gorilla, and very lower end in Homo,
      corresponding to disproportionately short thumbs and long medial digits in Homo.
      This suggests that manual proportions in Au. afarensis, particularly metacarpal
      proportions, were not as derived towards Homo as previously described, but rather
      are intermediate between gorillas and humans. Functionally, these results suggest
      Au. afarensis could not produce precision grips with the same efficiency as
      modern humans, which may in part account for the absence of lithic technology in
      this fossil taxon.

PMID- 24104948
TI  - Effective synthesis of kynurenine-containing peptides via on-resin ozonolysis of
      tryptophan residues: synthesis of cyclomontanin B.
AB  - The preparation of Kyn-containing peptides is difficult, owing to the low
      reactivity of Kyn in the coupling reaction. In this report, Kyn-containing
      peptides were efficiently obtained via on-resin ozonolysis of the corresponding
      Trp-containing peptide. In addition, a Kyn-containing cyclic peptide,
      cyclomontanin B, has been synthesized by this strategy in the combination with
      serine/threonine ligation (STL)-mediated cyclization. 

PMID- 24104949
TI  - [Practice guidelines for management of the difficult airway: update by the
      American Society of Anesthesiologists task force].
AB  - In February 2013 the Committee of the American Society of Anesthesiologists (ASA)
      Task Force published the amended version of the "Practice guidelines for
      management of the difficult airway" which replace the recommendations from 2003.
      The amended version re-evaluated the recommendations from 2003 in 2011, evaluated
      recently published studies and recommendations and included them in the new
      practice guidelines. In particular, new technical developments, such as the
      recently established video-assisted intubation procedure were taken into
      consideration. Despite the many publications in the field of airway management
      the evidence resulting from the data obtained from recent publications is so low
      that the new information does not necessitate any amendments to the existing
      guidelines. In short, the current guidelines basically correspond to the previous
      version published 10 years ago but are, however, more than twice as extensive.
      This article summarizes and comments on the cornerstones of the guidelines. 

PMID- 24104950
TI  - [Treatment gaps in acute pain therapy?: only a question of interpretation].

PMID- 24104951
TI  - How peer pressure shapes consensus, leadership, and innovations in social groups.
AB  - What is the effect of the combined direct and indirect social influences--peer
      pressure (PP)--on a social group's collective decisions? We present a model that
      captures PP as a function of the socio-cultural distance between individuals in a
      social group. Using this model and empirical data from 15 real-world social
      networks we found that the PP level determines how fast a social group reaches
      consensus. More importantly, the levels of PP determine the leaders who can
      achieve full control of their social groups. PP can overcome barriers imposed
      upon a consensus by the existence of tightly connected communities with local
      leaders or the existence of leaders with poor cohesiveness of opinions. A
      moderate level of PP is also necessary to explain the rate at which innovations
      diffuse through a variety of social groups.

PMID- 24104953
TI  - Cardiac motion and strain detection using 4D CT images: comparison with tagged
      MRI, and echocardiography.
AB  - Ischemic heart disease is a leading cause of death in the modern world. Coronary
      obstruction is the basis for ischemic heart disease and leads to decreased
      cardiac supply and decreased contractility of the myocardium. Recently, high
      quality 4D computed tomography (CT) has become available for cardiac imaging and
      provides the clinician with high quality anatomical images. In this article, a
      new method is proposed to detect 3D motion and strain from 4D cardiac CT images
      by constraining intensity constancy, myocardial volume changes and motion
      smoothness assumptions. The proposed method is validated by using manual tracking
      of the cardiac CT landmarks. The average error for the manual tracking, by an
      expert, was 2.9 +/- 0.9 mm. As an additional validation, the cardiac CT strain
      values were compared to the cardiac tagged magnetic resonance imaging (MRI) and
      2D B-mode echocardiography strain values of the same patients. The correlation
      ratio was significantly high for CT and tagged MRI radial strain values (r =
      0.76, 95% confidence interval, P < 0.001). The correlation ratio was meaningful
      for CT and echocardiography radial strain values as well (r = 0.67, 95%
      confidence interval, P < 0.001). The correlation ratio for CT and tagged MRI
      circumferential strain values was acceptable (r = 0.73, 95% confidence interval,
      P < 0.001), while the correlation ratio for CT and echocardiography
      circumferential strain values was good as well (r = 0.61, 95% confidence
      interval, P < 0.001). In general, motion and strain values computed from cardiac
      CT images agree with motion and strain values computed from tagged MRI and
      echocardiography images.

PMID- 24104952
TI  - Impact of white blood cell count on myocardial salvage, infarct size, and
      clinical outcomes in patients undergoing primary percutaneous coronary
      intervention for ST-segment elevation myocardial infarction: a magnetic resonance
      imaging study.
AB  - We sought to determine the relationship between white blood cell count (WBCc) and
      infarct size assessed by cardiovascular magnetic resonance imaging (CMR) in
      patients undergoing primary percutaneous coronary intervention (PCI) for ST
      elevation myocardial infarction (STEMI). In 198 patients undergoing primary PCI
      for STEMI, WBCc was measured upon arrival and CMR was performed a median of 7
      days after the index event. Infarct size was measured on delayed enhancement
      imaging and the area at risk (AAR) was quantified on T2-weighted images. Baseline
      characteristics were not significantly different between the high WBCc group
      (>11,000/mm(3), n = 91) and low WBCc group (<=11,000/mm(3), n = 107). The median
      infarct size was larger in the high WBCc group than in the low WBCc group [22.0%
      (16.7-33.9) vs. 14.7% (8.5-24.7), p < 0.01]. Compared with the low WBCc group,
      the high WBCc group had a greater extent of AAR and a smaller myocardial salvage
      index [MSI = (AAR-infarct size)/AAR * 100]. The major adverse cardiovascular
      events (MACE) including cardiac death, nonfatal reinfarction, and
      rehospitalization for congestive heart failure at 12-month occurred more
      frequently in the high WBCc group (12.1 vs. 0.9%, p < 0.01). In multivariate
      analysis, high WBCc significantly increased the risk of a large infarct (OR 3.04
      95% CI 1.65-5.61, p < 0.01), a low MSI (OR 2.08, 95% CI 1.13-3.86, p = 0.02), and
      1-year MACE (OR 16.0, 95% CI 1.89-134.5, p = 0.01). In patients undergoing
      primary PCI for STEMI, an elevated baseline WBCc is associated with less salvaged
      myocardium, larger infarct size and poorer clinical outcomes.

PMID- 24104954
TI  - Event-related potentials in substance use disorders: a narrative review based on
      articles from 1984 to 2012.
AB  - Mechanisms that mediate the transition from occasional, controlled, drug use to
      the impaired control that characterizes severe dependence are still a matter of
      investigation. The etiology of substance use disorders (SUDs) is complex, and in
      this context of complexity, the concept of "endophenotype," has gained extensive
      popularity in recent years. The main aim of endophenotypes is to provide a
      simpler, more proximal target to discover the biological underpinnings of a
      psychiatric syndrome. In this view, neurocognitive and neurophysiological
      impairments that suggest functional impairments associated with SUDs have been
      proposed as possible endophenotypes. Because of its large amplitude and
      relatively easy elicitation, the most studied of the cognitive brain event
      related potentials (ERPs), the P300 component, has been proposed as one possible
      candidate. However, if a P300 amplitude alteration is a common finding in SUDs,
      it is also observable in other psychiatric afflictions, suggesting that the
      associations found may just reflect a common measure of brain dysfunction. On
      this basis, it has been proposed that a multivariate endophenotype, based on a
      weighted combination of electrophysiological features, may provide greater
      diagnostic classification power than any single endophenotype. The rationale for
      investigating multiple features is to show that combining them provides extra
      useful information that is not available in the individual features, leading
      ultimately to a multivariate phenotype.The aim of the present article is to
      outline the potential usefulness of this kind of "combined electrophysiological
      procedure" applied to SUDs. We present a review of ERP studies, combining data
      from people with SUD, family members, and normal control subjects, to verify
      whether the combination of 4ERPs (P50, MMN, P300, and N400) may produce profiles
      of cortical anomalies induced by different types of SUD (alcohol vs cocaine vs
      cannabis vs heroin). 

PMID- 24104955
TI  - First evidence of a 200-day non-stop flight in a bird.
AB  - Being airborne is considered to be energetically more costly as compared with
      being on the ground or in water. Birds migrating or foraging while airborne are
      thought to spend some time resting on the ground or water to recover from these
      energetically demanding activities. However, for several decades ornithologists
      have claimed that some swifts may stay airborne for almost their whole lifetime.
      Here we present the first unequivocal evidence that an individual bird of the
      Alpine swift (Tachymarptis melba) can stay airborne for migration, foraging and
      roosting over a period of more than 6 months. To date, such long-lasting
      locomotive activities had been reported only for animals living in the sea. Even
      for an aerodynamically optimized bird, like the Alpine swift, flying requires a
      considerable amount of energy for continuous locomotive control. Our data imply
      that all vital physiological processes, including sleep, can be perpetuated
      during flight. 

PMID- 24104956
TI  - Intracellular cytokine and cathelicidin secretion from monocytes and neutrophils
      in childhood tuberculosis.
AB  - Human cathelicidin (hCAP 18) is one of the main immunomodulators in the local
      immune response to Mycobacterium tuberculosis. There has been no information
      regarding the role of hCAP 18+ in the in vivo production of cytokine in childhood
      pulmonary tuberculosis (TB). We aimed to determine the intracellular cytokine
      secretion, including hCAP 18+ from monocytes and neutrophils of pulmonary TB in
      children, compared with healthy children. Fifteen patients with pulmonary TB were
      enrolled in the study as the study group, and 15 healthy children as the control
      group, between the age of 1 and 16 years. The patients' 25 hydroxyvitamin D
      levels were measured. The expression of hCAP 18+, TNF alpha, INF-gamma and IL-8
      from CD14+ monocytes and CD15 + neutrophils was analyzed using the flow cytometry
      method. The statistical analysis was performed with PASW Statistics v.13.0. The
      mean vitamin D level was similar in both groups (P = 0.78). The expression of
      hCAP 18+ (P = 0.0001) and IL-8 from CD14 + (P = 0.0001) monocytes were
      significantly higher in the study group compared with the control group. There
      was no difference in the hCAP 18+ and IL-8 expression in CD 15+ neutrophils in
      both groups. The expression of TNF alpha, INF-gamma from CD14+ monocytes and CD
      15+ neutrophils, in both study and control groups revealed no statistical
      differences.The level of hCAP 18+ and IL-8 released from monocytes were enhanced
      in the serum in childhood pulmonary TB. The present study is the first report
      detecting the intracellular hCAP 18+ expression in vivo in childhood pulmonary
      TB. 

PMID- 24104957
TI  - Urinary tract infection in outpatient febrile infants younger than 30 days of
      age: a 10-year evaluation.
AB  - BACKGROUND: To determine the prevalence of outpatient-diagnosed urinary tract
      infection (UTI) in consecutive febrile neonates <= 30 days of age and correlate
      demographic, laboratory and radiographic imaging results with infectious
      etiology. METHODS: Review of medical records of consecutive febrile infants <= 30
      days of age presenting to an urban pediatric emergency department during a 10
      year period, whose policy is to perform a sepsis evaluation (urine culture
      obtained by bladder catheterization) and hospitalize for parenteral antibiotic
      therapy pending culture results. RESULTS: Of 670 febrile neonates <= 30 days of
      age evaluated for sepsis, urine culture was obtained in 651 cases (97%). Of 100
      patients with UTI (15.4%), 73% were male; the most common uropathogens were
      Escherichia coli (71%), Enterococcus (10%) and Klebsiella sp. (10%). In all, 39%
      had a maximum documented fever >= 102  degrees F, and 40% had CBC total white
      blood cells count >= 15,000/mm(3). Urine dipstick test was positive for leukocyte
      esterase or nitrite in 79%. Renal ultrasound performed in 95 patients (95%)
      showed anatomic abnormalities in 47%; 5/26 (24%) with hydronephrosis had
      vesicoureteral reflux on voiding cystourethrogram. Four patients had urosepsis;
      none had bacterial meningitis and no patients died. CONCLUSIONS: UTI affects
      approximately 1 in 6 febrile neonates <= 30 days of age. Males are affected 2.5
      times greater than females. E. coli continues to be the predominant uropathogen.
      Clinical parameters like height of fever, CBC total white blood cell count and
      urine dipstick test lack sensitivity in identifying UTI risk in the outpatient
      setting. Only 4 infants had urosepsis (4%). Nearly half of neonates with UTI have
      a radiographically identified anatomic abnormality. All febrile young infants
      should receive performance of a urine culture; those with UTI require imaging.

PMID- 24104958
TI  - Human parechovirus central nervous system infections in southern California
      children.
AB  - BACKGROUND: Human parechoviruses (hPeV) are increasingly recognized as
      significant etiological agents for meningoencephalitis especially in young
      children, but testing of cerebrospinal fluid (CSF) for hPeV by PCR is not
      routinely performed. METHODS: We used real-time reverse transcriptase PCR for
      detection of serotypes 1-6 in CSF samples of 440 children who underwent a lumbar
      puncture to exclude an infectious etiology of their clinical presentation. We
      then compared the prevalence and clinical presentation of children with hPeV
      positive CSF with that of children with enterovirus (EV)-positive CSF. RESULTS:
      HPeV was detected in 2.7% and EV in 10.7% of CSF samples. Many hPeV-positive
      patients were <3 months of age and usually had CSF parameters within the age
      adjusted normal range. However, children with hPeV-positive CSF presented with
      neurologic symptoms more frequently than those with EV-positive CSF. CONCLUSIONS:
      HPeV infections of the central nervous system occurred mainly in young infants
      and were more commonly associated with neurologic symptoms at presentation,
      despite the fact that CSF findings were within the normal range in the vast
      majority of these cases. HPeV should be included in the differential diagnosis of
      young children with central nervous system symptoms and sepsis-like illness, even
      in the presence of normal CSF parameters.

PMID- 24104960
TI  - [Development and first results of fast and cost-effective examination methods for
      an ophthalmological screening within the National Cohort].
AB  - BACKGROUND: For an implemented ophthalmological screening within a German long
      term cohort study (National Cohort) simple and effective methods for an
      examination of visual acuity and for non-mydriatic retina photografies should be
      evaluated. Furthermore standard operating-procedures (SOP) should be developed.
      METHODS: In the years 2011 and 2012 pinhole visual acuity measurements and
      automated retina photographies (DRS, CenterVue S. p. a., Padua, Italy) were made
      at three different epidemiological study centers within Germany. Furthermore,
      anterior segment images were taken by the camera. Standard operating procedures
      (SOP) regarding the ophthalmological screening were developed and evaluated
      within the study. The main question was whether it is possible to implement the
      screening methods within the National Cohort. Further main outcomes were quality
      and interpretability of the taken images. RESULTS: 457 subjects (914 eyes) were
      examined within the investigation. Median VA was 0.8 for right and left eyes (p >
      0.42). Image quality of the photographies was good in 491 cases (54 %), fair in
      239 cases (26 %) and bad in 179 cases (20 %). The usability of the images was
      without limitations in 686 cases (75 %), limited in 152 cases (17 %) and not
      given in 71 cases (8 %). Increasing age of the subjects was slightly correlated
      with decreasing image quality (r = 0.26) and decreasing image usability (r =
      0.2). Anterior segment photographies were usable in 176 eyes (56 %). CONCLUSION:
      The developed screening method fulfilled the specifications of the National
      Cohort. The used pinhole visual acuity examination was fast and cheap. Image
      quality and usability of the retina photographies could be improved with
      prolonged pupil recovery times. The quality of the anterior segment images could
      not fulfill the expectations and were taken out of the further examinations of
      the ophthalmological screening. The written SOP showed good acceptance within the
      investigators' daily routine. The ophthalmological screening within the National
      Cohort generates information (e. g., pathologies of the vessels or of the retina)
      which are useful not only from an ophthalmological point of view.

PMID- 24104959
TI  - George Feher: a pioneer in reaction center research.
AB  - Our understanding of photosynthesis has been greatly advanced by the elucidation
      of the structure and function of the reaction center (RC), the membrane protein
      responsible for the initial light-induced charge separation in photosynthetic
      bacteria and green plants. Although today we know a great deal about the details
      of the primary processes in photosynthesis, little was known in the early days.
      George Feher made pioneering contributions to photosynthesis research in
      characterizing RCs from photosynthetic bacteria following the ground-breaking
      work of Lou Duysens and Rod Clayton (see articles in this issue by van Gorkom and
      Wraight). The work in his laboratory at the University of California, San Diego,
      started in the late 1960s and continued for over 30 years. He isolated a pure RC
      protein and used magnetic resonance spectroscopy to study the primary reactants.
      Following this pioneering work, Feher studied the detailed structure of the RC
      and the basic electron and proton transfer functions that it performs using a
      wide variety of biophysical and biochemical techniques. These studies, together
      with work from many other researchers, have led to our present detailed
      understanding of these proteins and their function in photosynthesis. The present
      article is a brief historical account of his pioneering contributions to
      photosynthesis research. A more detailed description of his work can be found in
      an earlier biographical paper (Feher in Photosynth Res 55:1-40, 1998a).

PMID- 24104961
TI  - [Functional and morphological correlations in macular hole surgery].
AB  - BACKGROUND: The purpose of this study is to establish the correlation between
      functional and morphological aspects before and 12 months after macular hole
      surgery. METHODS: In this prospective, interventional, consecutive study 16 eyes
      of 16 patients were included. All eyes received a successful transconjunctival 23
      gauge vitrectomy with ILM peeling after initial diagnosis and maximum duration of
      symptoms of two months. Preoperatively and 3, 6 and 12 months postoperatively
      determinations of best-corrected visual acuity (logMAR), a 10 degrees 
      microperimetry (MP-1) and a spectral-domain based optical coherence tomography
      (SD-OCT) examination were performed. The photoreceptor layer (inner and outer
      segment, IS/OS) was evaluated based on SD-OCT images and correlated with data
      assessed by microperimetry analysis in the foveal and parafoveal region. RESULTS:
      After three months a stabilisation of BCVA with regeneration of the IS/OS line,
      an improvement of the fixation behaviour and the macular sensitivity could be
      observed. A significant restitution of the IS/OS line was observed after 12
      months. Best corrected visual acuity, mean overall macular sensitivity and
      fixation improved significantly within the twelve month observation period (p <
      0.05). Comparison of patients with at least two lines of visual acuity gain with
      patients having less than two lines of visual acuity gain 12 months after surgery
      showed no statistically significant difference in regeneration of the IS/OS
      integrity in the fovea (p = 0.433), but a difference was seen in the parafoveal
      region. A postoperative visual acuity gain of at least two lines was
      significantly more often seen in eyes with postoperative continuous IS/OS line in
      the parafoveal sectors compared to eyes with persistent IS/OS defects (p < 0.02).
      CONCLUSION: Correlations of morphological and functional improvements can be
      observed after successful micro-invasive macular hole surgery. The extent of the
      preoperative IS/OS defect, particularly in the parafoveal region, is a good
      predictive parameter for the postoperatively obtained macular sensitivity. The
      prediction of the postoperative visual acuity should not be made on the basis of
      a single clinical, anatomic finding.

PMID- 24104962
TI  - High-risk features in radiation-associated breast angiosarcomas.
AB  - BACKGROUND: Radiation-associated breast angiosarcoma (RT-AS) is an uncommon
      malignancy with an incidence of less than 1 % of all soft tissue sarcomas. The
      overall prognosis is quite dismal with high rates of recurrences and poor overall
      survival. There is an obvious paucity of data regarding clinical outcomes of
      patients with breast RT-AS. METHODS: We identified all patients with RT-AS
      treated at the Memorial Sloan-Kettering Cancer Center between 1982-2011 and
      collected their correlative clinical information. RESULTS: We identified 79 women
      with RT-AS with a median age of 68 (range 36-87). The median interval between
      radiation and development of RT-AS was 7 years (range 3-19). The median time to
      local and distant recurrence was 1.29 years (95 % CI 0.72-NA) and 2.48 years (95
      % CI 1.29-NA), respectively. The median disease-specific survival was 2.97 years
      (95 % CI 2.21-NA). Independent predictors of worse disease-specific survival
      included age ?68 years (HR 3.11, 95 % CI 1.20-8.08, P=0.020) and deep tumors (HR
      3.23, 95 % CI 1.02-10.21, P=0.046.) CONCLUSION: RT-AS has high local/distant
      recurrence rates, limited duration on standard chemotherapy and poor disease
      specific survival.

PMID- 24104963
TI  - Somatic copy number changes in DPYD are associated with lower risk of recurrence
      in triple-negative breast cancers.
AB  - BACKGROUND: Genomic rearrangements at the fragile site FRA1E may disrupt the
      dihydropyrimidine dehydrogenase gene (DPYD) which is involved in 5-fluorouracil
      (5-FU) catabolism. In triple-negative breast cancer (TNBC), a subtype of breast
      cancer frequently deficient in DNA repair, we have investigated the
      susceptibility to acquire copy number variations (CNVs) in DPYD and evaluated
      their impact on standard adjuvant treatment. METHODS: DPYD CNVs were analysed in
      106 TNBC tumour specimens using multiplex ligation-dependent probe amplification
      (MLPA) analysis. Dihydropyrimidine dehydrogenase (DPD) expression was determined
      by immunohistochemistry in 146 tumour tissues. RESULTS: In TNBC, we detected 43
      (41%) tumour specimens with genomic deletions and/or duplications within DPYD
      which were associated with higher histological grade (P=0.006) and with
      rearrangements in the DNA repair gene BRCA1 (P=0.007). Immunohistochemical
      analysis revealed low, moderate and high DPD expression in 64%, 29% and 7% of all
      TNBCs, and in 40%, 53% and 7% of TNBCs with DPYD CNVs, respectively. Irrespective
      of DPD protein levels, the presence of CNVs was significantly related to longer
      time to progression in patients who had received 5-FU- and/or anthracycline-based
      polychemotherapy (hazard ratio=0.26 (95% CI: 0.07-0.91), log-rank P=0.023;
      adjusted for tumour stage: P=0.037). CONCLUSION: Genomic rearrangements in DPYD,
      rather than aberrant DPD protein levels, reflect a distinct tumour profile
      associated with prolonged time to progression upon first-line chemotherapy in
      TNBC.

PMID- 24104964
TI  - MicroRNA-based molecular classification of non-BRCA1/2 hereditary breast tumours.
AB  - BACKGROUND: Hereditary breast cancer comprises 5-10% of all breast cancers.
      Mutations in two high-risk susceptibility genes, BRCA1 and BRCA2, along with rare
      intermediate-risk genes and common low-penetrance alleles identified, altogether
      explain no more than 45% of the high-risk breast cancer families, although the
      majority of cases are unaccounted for and are designated as BRCAX tumours. Micro
      RNAs have called great attention for classification of different cancer types and
      have been implicated in a range of important biological processes and are
      deregulated in cancer pathogenesis. METHODS: Here we have performed an
      exploratory hypothesis-generating study of miRNA expression profiles in a large
      series of 66 primary hereditary breast tumours by microarray analysis. RESULTS:
      Unsupervised clustering analysis of miRNA molecular profiles revealed distinct
      subgroups of BRCAX tumours, 'normal-like' BRCAX-A, 'proliferative' BRCAX-B,
      'BRCA1/2-like' BRCAX-C and 'undefined' BRCAX-D subgroup. These findings introduce
      a new insight in the biology of hereditary breast cancer, defining specific BRCAX
      subgroups, which could help in the search for novel susceptibility pathways in
      hereditary breast cancer. CONCLUSION: Our data demonstrate that BRCAX hereditary
      breast tumours can be sub-classified into four previously unknown homogenous
      groups characterised by specific miRNA expression signatures and
      histopathological features.

PMID- 24104965
TI  - Identification of serum miRNAs as novel non-invasive biomarkers for detection of
      high risk for early gastric cancer.
AB  - BACKGROUND: Many micro-RNAs (miRNAs) are differentially expressed in Helicobacter
      pylori-infected gastric mucosa and in gastric cancer tissue and previous reports
      have suggested the possibility of serum miRNAs as complementary tumour markers.
      The aim of the study was to investigate serum miRNAs and pepsinogen levels in
      individuals at high risk for gastric cancer both before and after H. pylori
      eradication. METHODS: Patients with recent history of endoscopic resection for
      early gastric cancer and the sex- and age-matched controls were enrolled. Serum
      was collected from subjects before or after eradication and total RNA was
      extracted to analyse serum levels of 24 miRNAs. Serum pepsinogen (PG) I and II
      levels were measured using enzyme-linked immunosorbent assay kits. RESULTS: Using
      miR-16 as an endogenous control, the relative levels of miR-106 and let-7d before
      and after H. pylori eradication and miR-21 after eradication were significantly
      higher in the high-risk group than in the controls. H. pylori eradication
      significantly decreased miR-106b levels and increased let-7d only in the control
      group. After eradication, the combination MiR-106b with miR-21 was superior to
      serum pepsinogen and the most valuable biomarker for the differentiating high
      risk group from controls. CONCLUSION: Serum miR-106b and miR-21 may provide a
      novel and stable marker of increased risk for early gastric cancer after H.
      pylori eradication.

PMID- 24104966
TI  - Sigma-2 receptor ligand as a novel method for delivering a SMAC mimetic drug for
      treating ovarian cancer.
AB  - BACKGROUND: The sigma-2 receptor has been validated as a biomarker for
      proliferating tumours. Second mitochondria-derived activator of caspase (Smac) is
      a protein released from mitochondria into the cytosol, leading to apoptosis. In
      this study, we investigated a sigma-2 ligand as a tumour-targeting drug delivery
      agent for treating ovarian cancer. METHODS: A sigma-2 ligand, SW 43, was
      conjugated with a Smac mimetic compound (SMC), SW IV-52s, to form SW III-123. The
      delivery function of the sigma-2 moiety and cell killing mechanisms of SW III-123
      were examined in human ovarian cancer cell lines. RESULTS: SW III-123
      internalisation into ovarian cancer cells was mediated by sigma-2 receptors. SW
      III-123, but not SW IV-52s or SW 43, exhibited potent cytotoxicity in human
      ovarian cancer cell lines SKOV-3, CaOV-3 and BG-1 after 24-h treatment,
      suggesting that the sigma-2 ligand successfully delivered SMC into ovarian cancer
      cells. SW III-123 induced rapid degradation of inhibitor of apoptosis proteins
      (cIAP1 and cIAP2), accumulation of NF-kappaB-inducing kinase (NIK) and
      phosphorylation of NF-kappaB p65, suggesting that SW III-123 activated both
      canonical and noncanonical NF-kappaB pathways in SKOV-3 cells. SW III-123 cleaved
      caspase-8, -9 and -3. Tumour necrosis factor alpha (TNFalpha) antibody markedly
      blocked SW III-123-induced cell death and caspase-3 activity in SKOV-3 cells,
      indicating that SW III-123 activated both intrinsic and extrinsic apoptotic
      pathways and induced TNFalpha-dependent cell death in SKOV-3 cells. CONCLUSION:
      Sigma-2 ligands are a promising tumour-targeting drug delivery agent. Sigma-2
      conjugated SMC exemplifies a novel class of therapeutic drugs for treating
      ovarian cancer.

PMID- 24104967
TI  - Recruitment of trimeric proliferating cell nuclear antigen by G1-phase cyclin
      dependent kinases following DNA damage with platinum-based antitumour agents.
AB  - BACKGROUND: In cycling tumour cells, the binary cyclin-dependent kinase
      Cdk4/cyclin D or Cdk2/cyclin E complex is inhibited by p21 following DNA damage
      to induce G1 cell-cycle arrest. However, it is not known whether other proteins
      are also recruited within Cdk complexes, or their role, and this was
      investigated. METHODS: Ovarian A2780 tumour cells were exposed to the platinum
      based antitumour agent 1R,2R-diaminocyclohexane(trans
      diacetato)(dichloro)platinum(IV) (DAP), which preferentially induces G1 arrest in
      a p21-dependent manner. The Cdk complexes were analysed by gel filtration
      chromatography, immunoblot and mass spectrometry. RESULTS: The active forms of
      Cdk4 and Cdk2 complexes in control tumour cells have a molecular size of ~140
      kDa, which increased to ~290 kDa when inhibited following G1 checkpoint
      activation by DAP. Proteomic analysis identified Cdk, cyclin, p21 and
      proliferating cell nuclear antigen (PCNA) in the inhibited complex, and
      biochemical studies provided unequivocal evidence that the increase in ~150 kDa
      of the inhibited complex is consistent with p21-dependent recruitment of PCNA as
      a trimer, likely bound to three molecules of p21. Although p21 alone was
      sufficient to inhibit the Cdk complex, PCNA was critical for stabilising p21.
      CONCLUSION: G1 Cdk complexes inhibited by p21 also recruit PCNA, which inhibits
      degradation and, thereby, prolongs activity of p21 within the complex.

PMID- 24104969
TI  - Calculating and assigning rovibrational energy levels of (15N2O)2, (15N14NO)2,
      14N2O-15N2O and 15N14NO-15N2O.
AB  - In this paper we report transition frequencies and rotational constants computed
      for several isotopologues of the nitrous oxide dimer. A previously reported
      intermolecular potential, the symmetry adapted Lanczos algorithm and an uncoupled
      product basis set are used to do the calculations. Rotational transition
      frequencies and rotational constants are in good agreement with experiment. We
      calculate states localized in both polar and nonpolar wells on the potential
      surface. Two of the four isotopologues we study have inequivalent monomers. They
      have wavefunctions localized over a single polar well. 

PMID- 24104968
TI  - Aurora kinase A (AURKA) expression in colorectal cancer liver metastasis is
      associated with poor prognosis.
AB  - BACKGROUND: Five-year survival after resection of colorectal cancer liver
      metastasis (CRLCM) is <30%. We recently found that aurora kinase A (AURKA) drives
      20q gain-associated tumour progression and is associated with disease recurrence.
      This study evaluates the prognostic value of AURKA expression in CRCLM of
      patients who underwent liver resection. METHODS: Tissue microarrays (TMAs) were
      generated using formalin-fixed paraffin-embedded CRCLM and matched primary tumour
      from a multi-institutional cohort of patients with CRCLM who underwent liver
      resection between 1990 and 2010. Tissue microarrays were stained for AURKA using
      immunohistochemistry, and a hazard rate ratio (HRR) for the association between
      overall survival (OS) and nuclear AURKA expression in CRCLM was calculated.
      Results were validated by 500-fold cross-validation. RESULTS: The expression of
      AURKA was evaluated in CRCLM of 343 patients. High AURKA expression was
      associated with poor OS (HRR 1.55, P<0.01), with a cross-validated average HRR of
      1.57 (P=0.02). Average HRR was adjusted for the established prognostic
      clinicopathological variables in a multivariate analysis (average HRR 1.66;
      P=0.02). The expression of AURKA in CRCLM was correlated to its expression in
      corresponding primary tumour (P<0.01). CONCLUSION: The expression of AURKA
      protein is a molecular biomarker with prognostic value for patients with CRCLM,
      independent of established clinicopathological variables.

PMID- 24104970
TI  - Cardiac changes with subclinical hypothyroidism in obese women.
AB  - OBJECTIVES: Obesity has been linked to a spectrum of minor cardiovascular
      changes. The aim of this study was to determine the effect of obesity on cardiac
      functions and its relations with subclinical hypothyroidism in healthy women.
      STUDY DESIGN: Eighty-eight consecutive "healthy" females (mean age: 31.2+/-6.6
      years) were included in the study. Thyroid function tests and echocardiography
      studies were performed in all patients. Height, weight, and waist and hip
      circumference were also measured. A body mass index (BMI) above 30 kg/m2 was
      considered obese. RESULTS: Left ventricular mass (LVM) was higher in obese
      subjects (p<0.001). Doppler-derived indices of LV diastolic filling showed clear
      abnormalities of myocardial relaxation in obese subjects with higher E/e'
      (p=0.001) and larger left atrial volume (LAV) (p<0.001). LV myocardial
      performance index was also significantly higher in obese subjects (p=0.033).
      Thyroid-stimulating hormone (TSH) levels were significantly higher in obese
      subjects (p=0.011) and were positively correlated with BMI, waist circumference,
      LAV, and LVM. The prevalence of abnormal systolic and diastolic functions showed
      stepwise increases with higher TSH levels in obese subjects. Multiple regression
      analysis was used to evaluate the association of E/e' with anthromorphometric and
      biochemical parameters, and waist circumference was found to be the strongest
      independent variable correlated with the E/e' ratio. CONCLUSION: Cardiac
      structural and functional deteriorations may be related with subclinical
      hypothyroidism in obese subjects.

PMID- 24104971
TI  - [Comparison of pneumatic compression device and sand bag with respect to
      peripheral vascular complications in elective cardiac catheterization and
      percutaneous femoral artery interventions].
AB  - OBJECTIVES: After coronary angiography and percutaneous coronary intervention
      (PCI), the classic sand bag method and compression devices are widely used for
      control of bleeding and prevention of vascular complications. The purpose of our
      study was to assess the major peripheral vascular complications and to compare
      the sand bag and a pneumatic compression device ("Close Pad") in terms of major
      peripheral vascular complications after coronary interventions. STUDY DESIGN:
      Between June 2011 and November 2011, a total of 434 patients who admitted to the
      Department of Cardiology of Uludag University Faculty of Medicine were included
      in the study. 396 patients underwent coronary angiography and 38 patients
      underwent PCI. Sand bag was applied in 209 patients. Bleeding requiring
      transfusion, hematoma larger than 10 cm(2), pseudoaneurysm, and arteriovenous
      (AV) fistula were defined as the major local complications. Logistic regression
      analysis were used to evaluate the datas. RESULTS: Major vascular complications
      occurred in 2% of diagnostic angiography and in 13.2% of PCI patients (p=0.003).
      The major vascular complications were significantly higher with the Close Pad
      device compared with sand bag (5.3% vs. 0.5%, p=0.007). Smoking, PCI, Close Pad,
      clopidogrel, and anticoagulants were observed to have increased risk of major
      local complications. In the logistic regression analysis, only smoking and Close
      Pad usage were evaluated as independent variables that increased the risk of
      major vascular complications (p<0.05). CONCLUSION: Close Pad usage demonstrated
      increased risk of vascular complications when compared with the sand bag in
      patients undergoing cardiac catheterizations. After the PCI, patients should be
      selected carefully for application of the Close Pad.

PMID- 24104972
TI  - Predictors and long-term prognostic significance of angiographically visible
      distal embolization during primary percutaneous coronary intervention.
AB  - OBJECTIVES: We aimed to identify the predictors of angiographically visible
      distal embolization (AVDE) during primary percutaneous coronary intervention (p
      PCI) as well as to assess its impact on short- and long-term clinical outcomes in
      patients with acute ST-segment elevation myocardial infarction (STEMI). STUDY
      DESIGN: We retrospectively enrolled 2007 patients with STEMI who underwent p-PCI.
      We assessed the clinical and angiographic characteristics of patients in order to
      identify the predictors of AVDE and compared the outcomes of patients with and
      without AVDE during p-PCI. RESULTS: Distal embolization developed in 135 (6.7%)
      patients. Age (for each 10- year increase, Odds Ratio (OR) 1.34, 95% Confidence
      Interval (CI) 1.16-1.52, p<0.001), treatment of right coronary artery (OR 2.52,
      95% CI 1.30-4.87, p=0.034), repeated balloon dilatation (OR 1.84, 95% CI 1.16
      2.94, p=0.009), cut-off occlusion pattern (OR 2.17, 95% CI 1.38-3.42, p=0.001),
      lesion length >15 mm (OR 1.67, 95% CI 1.09-2.58, p=0.019), and reference vessel
      diameter >3.5 mm (OR 5.08, 95% CI 3.32-7.65, p<0.001) were independent predictors
      of AVDE. In-hospital (8.1% vs. 3.8%, p=0.014) and one-month (10.8% vs. 4.9%,
      p=0.004) all-cause mortality rates were higher in patients with AVDE. At the long
      term follow-up (median: 42 months), both all-cause (21.5% vs. 10.4%, p<0.001) and
      cardiac mortality rates (18.4% vs. 8.0%, p<0.001) were higher in patients with
      AVDE. CONCLUSION: AVDE is associated with worse clinical outcome at both the
      short- and long-term follow-up of STEMI patients treated early with p-PCI.

PMID- 24104973
TI  - Distal embolization during primary percutaneous coronary interventions.

PMID- 24104974
TI  - Efficacy and benefits of catheter ablation of ventricular premature complexes in
      patients younger and older than 65 years of age.
AB  - OBJECTIVES: Catheter ablation of ventricular premature complexes (VPC) improves
      clinical status and systolic performance of the left ventricle (LV) in a certain
      subset of patients; however, whether or not VPC ablation is equally effective in
      younger (<=65 years) and older (>65 years) patients remains unclear. We aimed to
      assess the clinical benefits of catheter ablation of VPCs in elderly patients.
      STUDY DESIGN: Fifty-one consecutive patients (66+/-10 years, 49 male) who
      underwent catheter ablation for symptomatic VPCs were included into the study.
      Twenty-seven patients were aged >65 years and 24 patients <=65 years. Frequency
      of VPCs per total heart beats by 24-hour Holter monitoring, LV ejection fraction
      (LVEF) and end-systolic diameters (LVEDD) were evaluated before and 6+/-3 months
      after ablation. RESULTS: The pre-ablation 24-hour VPC burden and VPC number were
      significantly higher in patients >65 years compared to those <=65 years (31+/
      15.3 vs. 21.9+/-12.6, p=0.04 and 34493+/-21226 vs. 23554+/-13792, p=0.026,
      respectively). At the follow-up after catheter ablation, the mean VPC burden had
      decreased to 9.1+/-10.3% (p<0.001) in patients >65 years and to 3.8+/-7.1
      (p<0.001) in patients <=65 years. Mean LVEF showed a significant increase in both
      groups after ablation (43.4+/-10.4 vs. 51.5+/-8.2, p=0.005 for age >65 years and
      40.8+/-13.2 vs. 49.5+/-11.8, p=0.003 for age <=65 years). The improvement in LVEF
      was accompanied by a significant decrease in LVEDD (p=0.032 for age >65 years and
      p=0.047 for <=65 years). CONCLUSION: Catheter ablation is effective for treatment
      of frequent VPCs in all age groups.

PMID- 24104975
TI  - Results of percutaneous coronary intervention for chronic total occlusions of
      coronary arteries: a single center report.
AB  - OBJECTIVES: Percutaneous coronary intervention (PCI) for chronic total occlusions
      (CTOs) is associated with lower rates of procedural success and higher
      complication rates compared with PCIs in non-CTO lesions. The purpose of this
      study was to analyze the relationship between lesion characteristics and
      procedural success rates and in-hospital outcomes after PCI for CTO with novel
      equipment. STUDY DESIGN: We evaluated the prospectively entered data of 63
      consecutive patients undergoing PCI for CTO at our institute between August 2009
      and June 2012. RESULTS: A total of 63 patients (mean age: 64+/-11, 71% male) with
      one CTO lesion each underwent PCI. There were 46 patients (mean age: 63+/-10, 70%
      male) in the CTO success group and 17 patients (mean age: 65+/-13, 76.5% male) in
      the CTO failure group. Successful revascularization was achieved in 73% of
      patients. We used antegrade approach in 61 cases and retrograde approach in 2
      cases. Our predominant strategy was single-wire technique, which was used in 54
      cases (85.7%), followed by parallel-wire technique in 7 cases (11.1%). Moderate
      to-severe tortuosity (odds ratio [OR]: 9.732, 95% confidence interval [CI]: 1.783
      53.115, p=0.009) and occlusion duration (OR: 1.536, 95% CI: 1.178-2.001, p=0.002)
      were independent predictors of procedural failure in the multivariate analysis.
      No in-hospital major cardiac events occurred. CONCLUSION: We have reported a
      study with a relatively high success rate of PCI with very low procedural and in
      hospital complications. Moderate-to-severe tortuosity was observed as the most
      challenging problem despite the utilisation of novel equipment and techniques for
      CTO recanalization.

PMID- 24104976
TI  - Success in chronic total occlusion: "benefit for the patient" or "satisfaction
      for the operator"?

PMID- 24104977
TI  - Effect of overweight on P-wave and QT dispersions in childhood.
AB  - OBJECTIVES: The effects of obesity on atrial conduction and ventricular
      repolarization have been studied in detail, but these parameters have not been
      well documented in overweight children. The aim of our study was to investigate
      the effects of overweight on atrial conduction and ventricular repolarization in
      children by using P-wave dispersion (Pw-d) and QT dispersion (QT-d) analyses.
      STUDY DESIGN: Sixty-seven overweight children and 70 children within normal
      limits were included in this cross-sectional prospective controlled study. All
      subjects underwent electrocardiographic and anthropometric evaluation, and blood
      samples were obtained. Pw-d and QT-d were investigated between two groups.
      RESULTS: Homeostatic model assessment of insulin resistance levels were higher in
      the overweight group (2.9+/-1.2 vs. 1.1+/-0.8, p=0.001). No statistically
      significant differences were found in Pw-d and QT-d when the groups were
      compared. The following findings were recorded for the overweight and control
      groups, respectively: mean RR interval (635+/-42 msec vs. 645+/-45 msec,
      p=0.867), Pw-d [30 (10-55) msec vs. 27.5 (15-50) msec, p=0.441] and QT-d (30 (15
      55) msec vs. 22.5 (10-60) msec, p=0.476). In addition, Pw-d and QT-d were not
      correlated with the levels of insulin or body mass index. CONCLUSION: There was
      no significant difference in atrial conduction or ventricular repolarization
      features between overweight children and normal-weight children.

PMID- 24104978
TI  - Safe right bundle branch block pattern during permanent right ventricular pacing:
      a case report.
AB  - We present the case of a 72-year-old male who underwent a permanent transvenous
      DDD pacemaker implantation for symptomatic complete heart block. The
      postoperative surface electrocardiogram (ECG) revealed a right bundle branch
      block (RBBB) pacing pattern with transition in lead V3 and left bundle branch
      block (LBBB) in D1, suggesting a malpositioned ventricular lead in the left
      heart. Malposition of a lead was ruled out by chest X-ray and echocardiogram
      confirming apical right ventricular pacing. After a literature review, a surface
      ECG maneuver, by placing leads V1 and V2 one intercostal space lower, restored
      the usual patterns of paced LBBB pattern. We discuss the literature concerning
      safe-paced RBBB. 

PMID- 24104979
TI  - An unusual cause of spontaneous hemothorax: cardiac angiosarcoma.
AB  - Angiosarcoma, the most common primary malignant neoplasm of the heart in adults,
      usually presents as pericardial effusion or right-sided heart failure. Rupture of
      an angiosarcoma-infiltrated cardiac chamber as a cause of hemothorax is very rare
      in the literature. In this report, we describe a 34-year-old male patient, who
      presented to emergency service with sudden chest pain and dyspnea. The diagnostic
      work-up revealed spontaneous right-sided hemothorax and a large right atrial (RA)
      mass with suspicious atrial perforation. An urgent surgery showed a vascularized
      irregular RA mass invading the parietal pericardium and pleura and a perforation
      of the RA free wall. Histopathologic examination confirmed the diagnosis of
      angiosarcoma, and the patient was subsequently referred for radiotherapy and
      chemotherapy. 

PMID- 24104980
TI  - [Severe thrombosis of bioprosthesis mitral valve after dabigatran].
AB  - A 41-year-old female was admitted to our hospital with an unidentified source of
      fever, dyspnea and dizziness. Transthoracic echocardiography demonstrated severe
      mitral valve regurgitation, and further examination with transesophageal
      echocardiography (TEE) revealed a 7 mm vegetation on the anterior mitral leaflet.
      Blood cultures were negative, and after 45 days of empiric 12 g/day ampicillin
      sulbactam therapy, the vegetation was shown to have disappeared. However, due to
      ongoing severe mitral regurgitation and valve deformity, a prosthetic metallic
      mitral valve replacement was performed. After the operation, TEE was performed
      again due to subfebrile fever; however, the valve was normal and blood cultures
      were negative. Because of the probable relapse risk of infective endocarditis,
      the preoperative intravenous antibiotherapy was continued for 21 days and then
      orally for one week. Then, she was placed on follow-up by our outpatient clinic.
      As her INR was highly unstable during this period and she developed new-onset
      subfebrile fever, she was hospitalized again, and the TEE demonstrated
      vegetation. Blood cultures were still negative, and a combination of vancomycin
      rifampicin-gentamicin was started. While under that therapy, first stroke and
      after a few days recurrent trans-ischemic attack developed, and the vegetation
      was seen to have enlarged. Urgent valve operation was performed with a
      bioprosthetic mitral valve, and ampicillin-sulbactam therapy was added to her
      previous antibiotherapy at the suggestion of the Microbiology Department. Oral
      anticoagulant therapy was planned for three months; however, during the
      postoperative period, her INR levels were highly unstable and could not be
      maintained in therapeutic ranges for even two consecutive days. Adjusted dosage
      of dabigatran to 110 mg/bid according to renal clearance in combination with 150
      mg/day aspirin was started. However, valve thrombosis and a massive stroke
      developed under this therapy. The thrombosis disappeared after continuous heparin
      infusion, and she was discharged with neurological sequelae on 150 mg/day aspirin
      55 days after her last operation. During the follow-up period of four months, no
      other clinical events occurred. 

PMID- 24104981
TI  - A case of renal artery embolism treated by selective intra-arterial infusion of
      tissue plasminogen activator.
AB  - Thromboembolic obstruction of the renal artery is a serious clinical problem, but
      rarely diagnosed. The diagnosis is not usually established until irreversible
      renal parenchymal damage occurs. Here, we present a case of renal artery
      thromboembolism in a patient who had atrial fibrillation and was treated by
      selective intra-arterial infusion of tissue plasminogen activator (TPA). A 69
      year-old male was admitted to our hospital with a one-hour history of palpitation
      and epigastric pain. He had inferior myocardial infarction and percutaneous
      coronary intervention to the right coronary artery two weeks before. Coronary
      angiogram was performed, and no significant stenosis was detected. One hour
      later, epigastric pain spread to the left flank region. Spiral computerized
      tomography showed occlusion of the left renal artery. Emergency abdominal
      angiography was performed, and selective intra-arterial infusion of TPA was
      started promptly. The abdominal pain disappeared, and urine output remained
      adequate. Forty-eight hours later, angiographic follow-up confirmed the complete
      lysis of the thrombus in the left renal artery. No renal or hemorrhagic
      complications were observed, and the patient was discharged four days later with
      normalized renal function on oral anticoagulation. 

PMID- 24104982
TI  - [Monomorphic ventricular tachycardia during the ajmaline test].
AB  - A 44-year-old male patient admitted with palpitations was diagnosed with
      tachycardia with wide QRS, but recovered after being treated with amiodarone. The
      patient's coronary angiography was normal. As the patient's resting ECG was
      compatible with Brugada type 2, an ajmaline challenge test was scheduled. The
      infusion procedure was suspended following an observation of type 1 ECG findings
      in the 4th minute of infusion. Approximately 10-15 seconds later, a monomorphic
      ventricular tachycardia with a rate of 150 beats/minute developed. In the follow
      up, the patient's heartbeat returned spontaneously to the sinus rhythm within 3-4
      minutes. Polymorphic ventricular tachycardia or ventricular fibrillation
      tachyarrhythmias usually result in syncope or sudden cardiac death in cases of
      Brugada syndrome, while monomorphic tachycardia, as in our case, is rare. Here,
      we present a rare case of monomorphic ventricular tachycardia, which was observed
      during the ajmaline challenge test. 

PMID- 24104983
TI  - [Right atrial perforation after an endocardial screw-in atrial lead
      implantation].
AB  - A 24-year-old female underwent implantation of a right-sided dual chamber
      permanent pacemaker for cardioinhibitory syncope with active fixation atrial
      lead. Five days after the procedure, the patient developed pleuritic chest pain
      and difficulty in breathing. Minimal pericardial effusion and right
      hemopneumothorax were found. The atrial active screw-in lead was visualized just
      above the right atrial appendage with its helix perforating the right atrial
      wall, pericardium and pleura, reaching the right mid-lobe. Lead extraction was
      performed, and a passive bipolar atrial lead was implanted during the same
      session without any problems. 

PMID- 24104984
TI  - [Cardiac resynchronization therapy in heart failure patients with atrial
      fibrillation].
AB  - Despite advances in treatment, heart failure (HF) remains a highly prevalent,
      worldwide problem with a high morbidity and mortality. Cardiac resynchronization
      therapy (CRT) has become an essential therapeutic tool in HF patients with
      significant dyssynchrony due to intrinsic conduction disease. Although the
      prevalence of atrial fibrillation (AF) in patients with advanced HF is high,
      those patients are excluded or underrepresented in most of the CRT trails. In
      randomized studies supporting the benefits and indications for CRT, only 2% of
      patients had AF. Observational studies, a randomized trial and several meta
      analyses showed that HF patients with AF may experience benefits similar to
      patients with a sinus rhythm in terms of functional capacity and reverse
      remodeling, quality of life, and even survival. With this review, it was aimed to
      discuss the clinical issues related to CRT, efficacy, heart rate control
      strategies, and their effects on the therapy. 

PMID- 24104985
TI  - [How to interpret the results of pulmonary function tests?].

PMID- 24104986
TI  - Malignant ventricular arrhythmia as the first manifestation of cardiac
      sarcoidosis.

PMID- 24104987
TI  - "Windsock caught amidst a sandstorm" - echocardiographic images of a patient with
      ruptured sinus of Valsalva aneurysm.

PMID- 24104988
TI  - Three-vessel myocardial bridging causing severe angina.

PMID- 24104989
TI  - Criss-cross heart with atrial inversion and juxtaposed atrial appendages: an
      echocardiographic study.

PMID- 24104990
TI  - Angiographically detectable infracardiac TAPVC in a 7-month-old patient who had
      single ventricle physiology and left modified Blalock-Taussig shunt,
      dextrocardia, and large midline liver.

PMID- 24104991
TI  - Single port surgery for rectal cancer-going up or down?

PMID- 24104992
TI  - A lesson in continence from spinal cord injury.

PMID- 24104993
TI  - Resection of rectal cancer via an abdominal single-port access: short-term
      results and comparison with standard laparoscopy.
AB  - BACKGROUND: Rectal surgery via a single-port access is complex with unknown
      benefits. OBJECTIVE: This study aimed to compare the short-term outcome between
      single-port and multiport procedures. DESIGN: We undertook a retrospective
      analysis of prospectively collected data in a large, tertiary care cancer center
      in France. PATIENTS: From November 2008 to June 2012, 45 patients underwent a
      sphincter-saving rectal resection through a single-port (n = 13) or a multiport
      (n = 32) approach. The single-port approach used an abdominal single port (n = 6)
      alone or a combined abdominal and transanal single port (n = 7). MAIN OUTCOME
      MEASURES: This study analyzed the morbidity, mortality, pain, and quality of the
      oncologic resection. RESULTS: The groups had a similar median operative time (290
      vs 280 minutes, p = 0.54) and conversion rates (8% vs 6%, p = 0.90). No mortality
      occurred, and there was no difference in major morbidity (23% vs 16%, p = 0.50),
      anastomotic leakage (8% vs 9%, p = 1), or the length of the hospital stay (12 vs
      14 days, p = 0.23). The median pain score was lower on postoperative day 2 in the
      single-port group (1.5 vs 4, p = 0.01). The 2 groups had similar quality criteria
      for oncologic resection, namely the median number of harvested lymph nodes (14 vs
      15, p = 0.63), a good mesorectal dissection rate (85% vs 75%, p = 0.56), and
      positive resection margins (0% vs 6%, p = 0.10). LIMITATIONS: This study's
      limitations include the retrospective nature of the data and the small number of
      patients. CONCLUSIONS: Rectal cancer surgery through a single-port access is
      feasible with similar outcomes and less postoperative pain than with multiport
      laparoscopy.

PMID- 24104994
TI  - Serrated polyposis: colonic phenotype, extracolonic features, and familial risk
      in a large cohort.
AB  - BACKGROUND: Serrated polyposis is a poorly understood and likely underdiagnosed
      condition. Little is known regarding the colorectal cancer risk, extracolonic
      phenotype, and cause of serrated polyposis. OBJECTIVE: The aim of this study is
      to describe the clinical and family history features of a large cohort of
      individuals with serrated polyposis. DESIGN: This is a retrospective cohort study
      from 2 prospectively collected registries. PATIENTS: Patients meeting the updated
      2010 World Health Organization criteria for serrated polyposis were included.
      MAIN OUTCOME MEASURES: We report descriptive statistics for clinical and family
      history factors. RESULTS: A total of 52 individuals met criteria for serrated
      polyposis. Of these, one had Lynch syndrome and was not included in the
      statistical analyses. Median age at serrated polyposis diagnosis was 51 years
      (range, 18-77). Twenty-four (47%) patients were male, and 25 (49%) had a history
      of smoking. Two hundred sixty-eight lower endoscopic procedures were performed;
      42 (82%) patients had colorectal adenomas, 8 (16%) had a personal history of
      colorectal cancer (only 1 was diagnosed during follow-up), 12 (24%) had
      extracolonic tumors (4 had more than 1 primary tumor), and 19 (37%) reported a
      family history of colorectal cancer. Esophagogastroduodenoscopy in 30 individuals
      revealed only 1 (3%) with unexplained gastroduodenal polyps. No association was
      found between colorectal cancer diagnosis and sex, age at serrated polyposis
      diagnosis, extracolonic tumor, history of adenoma, or smoking status.
      LIMITATIONS: This was a retrospective study with no comparison groups.
      CONCLUSIONS: Gastroduodenal polyps are uncommon and likely not associated with
      serrated polyposis. Although extracolonic tumors were common in our cohort, it is
      still unclear whether these are associated with serrated polyposis. Our data,
      along with previous studies, support an association between serrated polyposis
      and smoking. Further work is still needed to clarify the effect of smoking on
      polyp development/progression in serrated polyposis.

PMID- 24104995
TI  - Statin therapy is associated with improved pathologic response to neoadjuvant
      chemoradiation in rectal cancer.
AB  - BACKGROUND: Achieving a pathologic complete response to neoadjuvant
      chemoradiation improves prognosis in rectal cancer. Statin therapy has been shown
      to enhance the impact of treatment in several malignancies, but little is known
      regarding the impact on rectal cancer response to neoadjuvant chemoradiation.
      OBJECTIVE: The purpose of this study was to determine whether statin use during
      neoadjuvant chemoradiation improves pathologic response in rectal cancer. DESIGN:
      This was a retrospective cohort study based on data from a prospectively
      maintained colorectal cancer database. The 2 cohorts were defined by statin use
      during neoadjuvant chemoradiation. SETTING: This study was performed at a single
      tertiary referral center. PATIENTS: Four hundred seven patients with primary
      rectal adenocarcinoma who underwent neoadjuvant therapy then proctectomy between
      2000 and 2012 were included. Ninety-nine patients (24.3%) took a statin
      throughout the entire course of neoadjuvant therapy. MAIN OUTCOME MEASURES: The
      primary outcome measure was pathologic response to neoadjuvant chemoradiotherapy
      as defined by the American Joint Committee on Cancer tumor regression grading
      system, grades 0 to 3. RESULTS: Patients in the statin cohort had a lower median
      regression grade (1 vs 2, p = 0.01) and were more likely to have a better
      response (grades 0-1 vs 2-3) than those not taking a statin (65.7% vs 48.7%, p =
      0.004). Statin use remained a significant predictor of an American Joint
      Committee on Cancer grade 0 to 1 (OR, 2.25; 95% CI, 1.33-3.82) in multivariate
      analyses. Although statin use itself did not significantly improve oncologic
      outcomes, an American Joint Committee on Cancer grade 0 to 1 response was
      associated with statistically significant improvements in overall survival,
      disease-free survival, cancer-specific mortality, and local recurrence.
      LIMITATIONS: This was a retrospective study and subject to nonrandomization of
      patients and incorporated patients on variable statin agents and doses.
      CONCLUSIONS: Statin therapy is associated with an improved response of rectal
      cancer to neoadjuvant chemoradiation. These data provide the foundation for a
      prospective clinical trial.

PMID- 24104996
TI  - The efficacy of self-expanding metal stents for malignant colorectal obstruction
      by noncolonic malignancy with peritoneal carcinomatosis.
AB  - BACKGROUND: Although self-expanding metal stents for colorectal obstruction is
      preferred over emergency surgery, the efficacy of self-expanding metal stents in
      patients with malignant colorectal obstruction by a noncolonic malignancy with
      peritoneal carcinomatosis has not been demonstrated. OBJECTIVE: The aim of this
      study was to evaluate the survival and long-term clinical outcome of self
      expanding metal stents as the initial interventional approach in patients with
      malignant colorectal obstruction due to a noncolonic malignancy with peritoneal
      carcinomatosis. DESIGN: This is a retrospective study. SETTINGS: This study was
      conducted at 2 tertiary care academic medical centers in South Korea. PATIENTS:
      The patients were included who underwent self-expanding metal stent insertion for
      palliation of a malignant colorectal obstruction by a noncolonic malignancy with
      peritoneal carcinomatosis between July 2004 and January 2010. Inclusion criteria
      were incurable status, noncolorectal cancer, obstructive symptoms and/or signs,
      and colonoscopic findings of obstruction. MAIN OUTCOME MEASURES: The survival and
      success rate of patients undergoing self-expanding metal stents insertion was
      assessed. RESULTS: Twenty patients were included during the study period.
      Technical success of self-expanding metal stents was achieved in 18/20 (90.0%)
      patients, and obstructive symptoms were resolved within 72 hours in 17/20 (85.0%)
      patients. Ten patients (10/20, 50%) did not need further intervention during the
      follow-up period after the first stent insertion. Eight patients ultimately
      underwent surgery during the follow-up period. One of the remaining 2 patients
      underwent additional endoscopic treatment without surgery. Another patient
      refused further intervention and thus received conservative management. Mean
      event-free survival was 119.0 days, and the mean overall survival of the included
      patients was 156.3 days. LIMITATION: The number of study patients was small.
      CONCLUSION: Self-expanding metal stent insertion appears to be a reasonable first
      treatment option in patients with malignant colorectal obstruction by noncolonic
      malignancy with peritoneal carcinomatosis.

PMID- 24104997
TI  - Timing of colonoscopy after resection for colorectal cancer: are we looking too
      soon?
AB  - BACKGROUND: Based on current National Comprehensive Cancer Network guidelines,
      colonoscopic surveillance after colorectal cancer resection should begin at 1
      year. OBJECTIVE: The aim of this study was to determine whether the incidence of
      cancer or advanced polyp detection rate was high enough to justify colonoscopy at
      1 year. DESIGN: The Ochsner Clinic Tumor Registry Database was queried for
      patients who underwent a segmental colectomy or proctectomy between 2002 and
      2010. Patients who had a preoperative colonoscopy and at least 1 documented
      postoperative colonoscopy were included. We considered new cancer or polyps of
      >=1 cm as missed on the preoperative colonoscopy. Patients with an identified
      genetic trait causing a predisposition to colorectal cancer were excluded.
      RESULTS: Five hundred twelve patients underwent resection, and 155 met our
      inclusion criteria. The average age was 64 years, and 53% patients were male.
      There were 32.9% with stage I disease, 35% with stage II disease, 27.1% with
      stage III disease, and 5.2% with stage IV disease. Of these patients, 52.2% had a
      right colectomy, 7.1% had a left colectomy, 16.8% had a sigmoid colectomy, 22%
      had a low anterior resection, and 1.3% had a transanal resection. The average
      time to first postoperative colonoscopy was 478 days (SD +/-283 days). Twenty
      four patients had adenomatous polyps detected on their first surveillance
      colonoscopy, but only 5 (3.2%) polyps were >=1 cm, and there was no correlation
      between stage of cancer and finding a polyp. No new cancers were detected, but 3
      (1.9%) had an anastomotic recurrence. CONCLUSIONS: The performance of
      surveillance colonoscopy at 1 year resulted in the detection of only 5 missed
      polyps >=1 cm and no metachronous cancers. Anastomotic recurrences were rare, and
      the majority were in patients who had rectal cancer that could be evaluated by in
      office flexible sigmoidoscopy. Extending the time to first colonoscopy appears to
      be safe and would help conserve valuable resources, including physician and
      facility time, which is imperative in the current health care climate.

PMID- 24104998
TI  - High-resolution anoscopy: clinical features of anal intraepithelial neoplasia in
      HIV-positive men.
AB  - BACKGROUND: High-resolution anoscopy is increasingly advocated to screen HIV+ men
      who have sex with men for anal cancer and its precursor lesions, anal
      intraepithelial neoplasia. A systematic comparison between clinical features and
      the histopathology of suspect lesions is lacking. OBJECTIVE: This study aims to
      analyze interobserver agreement in classifying features of intra-anal lesions
      suspect for anal intraepithelial neoplasia and to compare these features with
      their histopathological outcome. DESIGN: This study is a cross-sectional survey
      regarding high-resolution anoscopy with images and biopsies of suspect lesions.
      Two dermatologists experienced in high-resolution anoscopy, blinded for
      histopathological outcome, independently classified the lesions on clinical
      features. SETTING: This investigation was conducted at the Dermatology outpatient
      clinic of the Academic Medical Center in Amsterdam, The Netherlands. PATIENTS:
      Included in the study were 163 HIV+ men who have sex with men, older than 18
      years, with no history of anal cancer. MAIN OUTCOME MEASURES: The primary
      outcomes measured were the kappa-coefficient for interobserver agreement and the
      proportions of anal intraepithelial neoplasia per clinical feature. RESULTS:
      Three hundred four biopsies were taken from 163 patients. One hundred sixty-eight
      biopsies (55%) showed anal intraepithelial neoplasia, and 67/304 (22%) showed
      high-grade anal intraepithelial neoplasia. The kappa-coefficient was 0.65 for
      condylomatous lesions, 0.14 for surface configuration, 0.54 for punctation, 0.08
      for mosaicism, and 0.43 for atypical vessels. Condylomatous lesions showed high
      grade anal intraepithelial neoplasia in 18% (95% CI, 11%-27%). In lesions with
      flat leukoplakia, punctation, and atypical vessels, high-grade anal
      intraepithelial neoplasia was seen in 25%, 30%, and 23%. In lesions with the
      combination punctation/atypical vessels and punctation/flat leukoplakia/atypical
      vessels, high-grade anal intraepithelial neoplasia was found in 38% and 40%.
      LIMITATIONS: We did not take biopsies of healthy-looking mucosa. Furthermore, the
      real-time description of features during high-resolution anoscopy, instead of the
      use of images, would improve the recognition of subtle mucosal abnormalities.
      CONCLUSIONS: A moderate to substantial interobserver agreement was demonstrated
      in recognizing condylomas, punctation, and atypical vessels. Furthermore, high
      grade anal intraepithelial neoplasia is present in a high proportion of intra
      anal condylomata. A combination of punctation, flat leukoplakia, and atypical
      vessels is the best predictor for high-grade anal intraepithelial neoplasia.

PMID- 24104999
TI  - Operative strategy modifies risk of pouch-related outcomes in patients with
      ulcerative colitis on preoperative anti-tumor necrosis factor-alpha therapy.
AB  - BACKGROUND: Whether preoperative biological therapy increases postoperative
      complications after restorative proctocolectomy remains controversial. OBJECTIVE:
      This study aims to evaluate the influence of preoperative use of biologics on
      outcomes after restorative proctocolectomy and to assess whether a staged
      approach modifies any negative influence of these medications. SETTING: The study
      was conducted at a single tertiary institution. DESIGN AND PATIENTS: Patients who
      were operated on for medically refractory ulcerative or indeterminate colitis
      were identified and classified by initial surgery, whether subtotal colectomy or
      total proctocolectomy, then categorized into biologics user and nonuser groups.
      Demographics, perioperative data, postoperative complications, pouch function,
      and quality of life were collected. OUTCOME MEASURE: Cumulative 1-year
      complication rates were estimated by using the Kaplan-Meier curve, and
      independent predictors for infectious complications were identified by using Cox
      proportional hazards regression models. RESULTS: From 2006 to 2010, 407 and 181
      patients underwent initial subtotal colectomy with end ileostomy or total
      proctocolectomy with IPAA. For the 181 patients who underwent total
      proctocolectomy straightaway, pre- and perioperative data were comparable for
      biologics users (n = 25) and nonusers (n = 156). Cumulative 1-year pelvic sepsis
      rate was significantly greater in patients on biologics (32% vs 16%, p = 0.012).
      Multivariate analysis demonstrated that preoperative anti-tumor necrosis factor
      therapy (HR, 2.62; p = 0.027) was an independent risk factor for postoperative
      pelvic sepsis after total proctocolectomy. After subtotal colectomy, no
      differences occurred in both 30-day and cumulative 1-year postoperative
      complications between biologics users (n = 142) and nonusers (n = 265). Outcomes
      were also similar when biologics users (n = 88) and nonusers (n = 164) underwent
      subsequent completion proctectomy with ileal pouch creation after initial
      colectomy. LIMITATIONS: The retrospective nature of this study and physician's
      preference were limitations. CONCLUSIONS: Preoperative exposure to biologics is
      associated with an increased risk of pelvic sepsis after total proctocolectomy
      with IPAA. This risk is mitigated by the performance of an initial subtotal
      colectomy.

PMID- 24105000
TI  - Impact of stress dose steroids on the outcomes of restorative proctocolectomy in
      patients with ulcerative colitis.
AB  - BACKGROUND: Stress dose steroids are administered during the perioperative period
      to prevent complications of secondary hypoadrenalism, which can occur after long
      term steroid treatment. Steroids also increase postoperative morbidity. Patients
      with ulcerative colitis often require steroid therapy before definitive surgery
      and often receive perioperative steroids in a variety of doses. OBJECTIVE: The
      aim of this study was to evaluate the impact of stress dose steroid
      administration on short-term postoperative outcomes after restorative
      proctocolectomy in patients with ulcerative colitis. DESIGN: This was a
      retrospective cohort study. SETTING: The investigation took place in a high
      volume, specialized colorectal surgery department. PATIENTS: Patients who had
      been treated with steroids for ulcerative colitis and underwent a restorative
      proctocolectomy from January 2009 to July 2011 were identified and categorized
      into 2 groups based on whether they received stress dose steroids. MAIN OUTCOME
      MEASURES: Both cohorts were compared for patient demographics, duration of
      steroid treatment before surgery, and operative and postoperative outcomes.
      RESULTS: Eighty-nine patients received stress dose steroids and 146 patients did
      not. Stress dose steroids were more frequently administered to patients who were
      under steroid treatment immediately before restorative proctocolectomy (37.1%
      versus 10.3%; p < 0.001). A sinus tachycardia developed more frequently in
      patients who received stress dose steroids during surgery (p = 0.03). One patient
      in the stress dose steroid group died on postoperative day 25 because of
      anastomotic leak. Although no patients in either group had an adrenal crisis
      during surgery, 1 patient in the stress dose steroid group was diagnosed with
      adrenal insufficiency postoperatively. LIMITATIONS: This study was limited by its
      retrospective and nonrandomized nature. CONCLUSIONS: Although administration of
      stress dose steroids is not related to increased postoperative complications, the
      steroids do not appear to affect adrenal insufficiency outcomes. Patients who
      were treated with steroids for ulcerative colitis should be monitored carefully
      in the perioperative and early postoperative periods for signs of adrenal
      insufficiency, regardless of the steroid regimen used.

PMID- 24105001
TI  - Colonoscopy following nonoperative management of uncomplicated diverticulitis may
      not be warranted.
AB  - BACKGROUND: Following the nonoperative management of acute diverticulitis,
      guidelines recommend routine follow-up colonoscopy; however, evidence to support
      this recommendation are lacking. OBJECTIVE: This study aims to determine the
      diagnostic yield of endoscopy for clinically significant neoplasia following the
      successful nonoperative management of acute diverticulitis. DESIGN: This study is
      a retrospective review. SETTING: This study was conducted in a large urban health
      region. PATIENTS: Adult patients who were admitted with a diagnosis of acute
      diverticulitis confirmed by CT and who were successfully managed nonoperatively
      to hospital discharge were included. Patients who underwent colonoscopy within 2
      years of presentation were excluded. MAIN OUTCOME MEASURE: The primary outcome
      measured was the incidence of clinically significant neoplasia (invasive
      malignancy or advanced adenoma) on follow-up endoscopy within 1 year of
      admission. RESULTS: Four hundred fifty-eight patients were selected for analysis,
      of which 249 patients (54%) underwent endoscopy within 1 year of admission.
      Seventy-seven (30.9%) patients were found to have polyps, 19 (7.6%) patients had
      advanced adenomas, and 4 (1.6%) patients had an invasive malignancy; 23 patients
      (9.2%) were found to have clinically significant neoplasia. On subgroup analysis,
      patients presenting with complicated diverticulitis (n = 74) had a significantly
      higher incidence of advanced adenoma (18.9% vs 5%, p = 0.001) and invasive
      malignancy (5.4% vs 0%, p = 0.007) in comparison with patients who presented with
      uncomplicated diverticulitis (n = 175). On multivariate analysis, patient age (OR
      1.04 (1.01-1.08), p = 0.02) and the presence of abscess (OR 4.15 (1.68-10.3), p =
      0.002) were identified as significant risk factors for clinically significant
      neoplasia. LIMITATIONS: The use of retrospective data was a limitation of this
      study; 54% of selected patients underwent endoscopic follow-up. CONCLUSIONS: The
      incidence of clinically significant neoplasia on endoscopic follow-up after the
      nonoperative management of acute diverticulitis is 9.2%. Those with complicated
      diverticulitis are at higher risk, whereas the incidence of clinically
      significant neoplasia in those with uncomplicated diverticulitis is equal to the
      incidence in average-risk individuals. Routine diagnostic colonoscopy following
      the nonoperative management of acute uncomplicated diverticulitis may not be
      warranted.

PMID- 24105002
TI  - Risk of morbidity, mortality, and recurrence after parastomal hernia repair: a
      nationwide study.
AB  - BACKGROUND: Surgical outcome results after repair for parastomal hernia are
      sparsely reported and based on small-scale studies. OBJECTIVE: This study aims to
      analyze surgical risk factors for 30-day reoperation and mortality, and,
      secondarily, to report the risk of reoperation for recurrence. DESIGN: This is a
      retrospective analysis of nationwide perioperative surgical variables. The
      primary outcome was reoperation for surgical complications and/or mortality
      within 30 days after parastomal hernia repair. Follow-up was obtained from the
      Danish National Patient Register. Detailed patient-related data were based on
      hospital files. Multivariate analysis was based on a compound parameter: 30-day
      reoperation or death. SETTING AND PATIENTS: All patients with a parastomal hernia
      repair registered in the Danish Hernia Database from January 1, 2007 to December
      31, 2010 were included. MAIN OUTCOME MEASURES: Univariate and logistic regression
      was used to identify risk factors for 30-day reoperation or death. RESULTS: The
      study included 174 patients with a parastomal hernia repair (142 elective and 32
      emergency repairs; 56 open and 118 laparoscopic repairs). Median follow-up was 20
      months (range, 0-47). A total of 13.2% were reoperated because of postoperative
      complications, and 6.3% of patients died within the first 30 postoperative days.
      Emergency repair was the strongest risk factor for reoperation or death in
      multivariate analyses (OR, 7.6; 95% CI, 2.7-21.5). No difference was found in
      preoperative risk of poor outcome between elective and emergency repairs
      (Charlson score 4 (range, 0-12) vs 5 (0-11), p = 0.07). After 3 years, the
      cumulated reoperation rate for recurrence was 10.8% (open 17.2% and laparoscopic
      3.8%). LIMITATIONS: Patients' comorbidity was based on retrospective data, and
      the study had a relatively short follow-up. CONCLUSION: In the present nationwide
      study, repair for a parastomal hernia was associated with high rates of
      morbidity, mortality, and repair for recurrence. Emergency repair was the only
      important risk factor to predict poor 30-day postoperative outcome.

PMID- 24105003
TI  - Fecal continence revisited: the anal external sphincter continence reflex.
AB  - BACKGROUND: None of the current theories on fecal incontinence can explain fecal
      continence adequately. OBJECTIVE: This study aims to evaluate the mechanism
      controlling fecal continence. DESIGN: Anal electrosensitivity, anorectal
      pressures, and rectal pressure volumetry tests were performed in 17 controls
      before and after superficial local anal anesthesia and in 6 controls before and
      after spinal anesthesia. The same tests were performed in 1 patient before and
      after injected local anal anesthesia and in 3 patients with spinal cord lesions
      at levels Th3 to L3. RESULTS: After superficial local anal anesthesia, anal
      electrosensitivity decreased, but basal anal pressure remained unaltered. Squeeze
      pressure decreased and rectal filling sensation levels remained. Local anesthesia
      reduced anal pressure recorded in the distal anal canal during progressive rectal
      filling. This was also the case, albeit more explicit, after the local anal
      anesthetic was injected. After spinal anesthesia, the anal canal became
      insensitive to electric stimulation, but basal and squeeze pressure values
      decreased substantially, and the increase in anal pressure during the balloon
      retaining test disappeared completely. In the patients with spinal cord lesions,
      the external sphincter could not be squeezed on command, but during the balloon
      retaining test, the anal sphincter did squeeze autonomously at more than 300
      mmHg. LIMITATIONS: These were partially experimental measurements. The relevance
      of the found model in the daily clinical practice will have to be studied in a
      following study. CONCLUSIONS: Our results support the hypothesis that the
      component of fecal continence mediated by contraction of the external sphincter
      depends on a anal external sphincter continence reflex without involving the
      brain. Presumably, the afferent receptors of this reflex are contact receptors
      located superficially in the mucosa or submucosa of the distal anal canal. A
      nonfunctioning anal external sphincter continence reflex would, therefore, result
      in fecal incontinence (see Video, Supplemental Digital Content 1,
      http://links.lww.com/DCR/A116).

PMID- 24105004
TI  - Anatomical disruption and length-tension dysfunction of anal sphincter complex
      muscles in women with fecal incontinence.
AB  - BACKGROUND: Anal sphincter complex muscles, the internal anal sphincter, external
      anal sphincter, and puborectalis muscles, play an important role in the anal
      continence mechanism. Patients with symptoms of fecal incontinence have weak anal
      sphincter complex muscles; however, their length-tension properties and
      relationship to anatomical disruption have never been studied. OBJECTIVE: This
      study aimed to assess the anatomy of the anal sphincter complex muscles with the
      use of a 3-dimensional ultrasound imaging system and to determine the
      relationship between the anatomical defects and the length-tension property of
      external anal sphincter and puborectalis muscles in women with incontinence
      symptoms and in control subjects. DESIGN: Severity of anal sphincter muscle
      damage was determined by static and dynamic 3-dimensional ultrasound imaging. The
      length-tension property was determined by anal and vaginal pressure with the use
      of custom-designed probes. PATIENTS: Forty-four asymptomatic controls and 24
      incontinent patients participated in this study. MAIN OUTCOME MEASURES: The
      anatomical defects and length-tension dysfunction of anal sphincter complex
      muscles in patients with fecal incontinence were evaluated. RESULTS: The
      prevalence of injury to sphincter muscles is significantly greater in the
      incontinent patients than in the controls. Eighty-five percent of patients but
      only 9% controls reveal damage to >=2 of the 3 muscles of the anal sphincter
      complex. Anal and vaginal squeeze pressures increased with the increase in the
      probe size (length-tension curve) in the majority of controls. In patients, the
      increase in anal and vaginal squeeze pressures was either significantly smaller
      than in controls or it decreased with the increasing probe size (abnormal length
      tension). LIMITATIONS: We studied patients with severe symptoms. Whether our
      findings are applicable to patients with mild to moderate symptoms remains to be
      determined. CONCLUSIONS: The length-tension property of the external anal
      sphincter and puborectalis muscles is significantly impaired in incontinent
      patients. Our findings have therapeutic implications for the treatment of anal
      incontinence.

PMID- 24105005
TI  - In vivo recovery of the injured anal sphincter after repair and injection of
      myogenic stem cells: an experimental model.
AB  - OBJECTIVE: This study aims to evaluate in vivo function of the external anal
      sphincter after transection and repair augmented with myogenic stem cells, and to
      establish normative electromyography parameters of the rodent external anal
      sphincter. DESIGN AND SETTING: Thirty-three Sprague-Dawley rodents underwent
      baseline needle electromyography of the external anal sphincter. Motor unit
      action potentials were obtained and normative parameters established. Animals
      were randomly assigned to a myogenic stem cell group (n = 24) or control group (n
      = 9). All underwent proctoepisiotomy. The control group underwent layered repair
      with phosphate-buffered saline injection to the external anal sphincter. The
      treatment group underwent identical repair with injection of myogenic stem cells
      5.0 * 10. Baseline anal pressure recordings were collected and repeated 2 weeks
      postintervention, and electromyography was repeated at 2 and 4 weeks. Groups were
      compared across 3 time points with the use of repeated measures ANOVA. MAIN
      OUTCOME MEASURES: The primary outcomes measured were the functional recovery of
      rat anal sphincters after stem cell transplantation as assessed by objective
      electromyography and anal pressure measures. RESULTS: A mean of 17 motor unit
      action potentials were sampled per animal. At 2 weeks postrepair, there was a
      significant difference between control and transplant groups with respect to
      amplitude, duration, turns, and phases (p < 0.01 for each). No significant
      electromyography differences were seen at 4 weeks. Resting and peak anal
      pressures declined significantly at 2 weeks postinjury in the control but not in
      the stem cell group. LIMITATIONS: Use of a murine animal population limited the
      subjective feedback and wider applicability. CONCLUSIONS: In vivo functional
      studies show recovery of anal sphincter pressures and electromyography to
      preinjury levels by day 14 in the myogenic stem cell group but not controls. At 4
      weeks, all electromyography parameters returned to baseline irrespective of
      group. Restoration of function may be accelerated by the transplantation of
      myogenic stem cells and associated trophic factors.

PMID- 24105006
TI  - Building a business case for colorectal surgery quality improvement.
AB  - BACKGROUND: Improving surgical quality is a priority, but building a business
      case for the efforts could be challenging. Bridging the gap between the
      clinicians and hospital leaders is the first step to align quality and financial
      priorities within health care. OBJECTIVE: The aim of this study was to evaluate
      the financial impact of the surgical comprehensive unit-based safety program on
      colorectal surgery procedures. DESIGN: This a retrospective cohort study.
      SETTING: This study was conducted at a university-based tertiary care hospital.
      PATIENTS: All patients undergoing colectomy or proctectomy between July 2010 and
      June 2012 were included. INTERVENTION: A comprehensive unit-based safety program
      focused on colorectal surgical site infection reduction was implemented. Three
      surgeons participated in the program in year 1, and 5 surgeons participated in
      year 2. Patients were categorized as participating or nonparticipating based on
      the surgeon who performed the procedure. MAIN OUTCOME MEASURES: Resource
      utilization and cost were the main outcome measures. RESULTS: During the 2 years,
      there were 626 patients who met the selection criteria. Participating surgeons
      operated on 444 patients (70.9%), and the nonparticipating surgeons operated on
      182 patients (29.1%). After adjusting for covariates, the variable direct cost
      was significantly lower for the participating surgeons in laboratory work by $191
      (p = 0.009), operating room utilization by $149 (p = 0.05), and supplies by $615
      (p = 0.003). The surgical site infection rates, need for an intensive care unit
      stay, and length of stay were not significantly different between the 2 groups.
      LIMITATIONS: The multiple biases related to surgeon self-selection for program
      participation and surgeon training and clinical skills were not addressed in this
      study owing to the limitations in sample size and data collection. CONCLUSION: A
      comprehensive unit-based safety program implementation, including dedicated
      frontline providers who focused on the standardization of protocols, was able to
      reduce the variation in resource utilization and costs in comparison with a
      control group.

PMID- 24105008
TI  - The tissue-selecting technique: segmental stapled hemorrhoidopexy.
AB  - We describe a technique for the management of prolapsing hemorrhoids, with the
      aim to minimize the risk of anal stricture and rectovaginal fistula and to reduce
      the impact of the stapling technique on rectal compliance. This modified
      procedure was successfully applied in China, and preliminary data showed
      promising outcomes (see Video, Supplemental Digital Content 1,
      http://links.lww.com/DCR/A117). 

PMID- 24105007
TI  - Diabetes mellitus and colorectal cancer prognosis: a meta-analysis.
AB  - BACKGROUND: Diabetes mellitus is associated with an increased incidence of
      colorectal cancer, but the impact of diabetes mellitus on colorectal cancer
      prognosis is not clear. OBJECTIVE: We conducted a meta-analysis of observational
      studies to examine the association between preexisting diabetes mellitus and
      colorectal cancer all-cause mortality, cancer-specific mortality, and recurrence.
      DATA SOURCES: Medline and Embase were searched through August 22, 2012. STUDY
      SELECTION: We included studies reporting all-cause mortality, cancer-specific
      mortality, disease-free survival, or recurrence in patients who have colorectal
      cancer according to diabetic status. INTERVENTION: Meta-analyses were performed
      by the use of random-effects models. MAIN OUTCOME MEASURES: The primary outcomes
      measured were all-cause mortality, cancer-specific mortality, and disease-free
      survival. RESULTS: Twenty-six articles met our inclusion criteria. Patients with
      colorectal cancer who had diabetes mellitus had a 17% increased risk of all-cause
      mortality (relative risk, 1.17; 95% CI, 1.09-1.25) and a 12% increased risk of
      cancer-specific mortality (relative risk, 1.12; 95% CI, 1.01-1.24) in comparison
      with those who did not have diabetes mellitus. Those with diabetes mellitus also
      had poorer disease-free survival (relative risk, 1.54; 95% CI, 1.08-2.18)
      compared with their nondiabetic counterparts. In subgroup analyses, diabetes
      mellitus was associated with all-cause mortality in both rectal (relative risk,
      1.24; 95% CI, 1.07-1.29) and colon cancer patients (relative risk, 1.17; 95% CI,
      1.07-1.29). Sensitivity analyses including only patients with nonmetastatic
      disease identified stronger associations between diabetes mellitus and both all
      cause (relative risk, 1.32; 95% CI, 1.21-1.44) and cancer-specific (relative
      risk, 1.27; 95% CI, 1.06-1.52) mortality. LIMITATIONS: Some studies had short
      follow-up or did not report mean or median follow-up. The included studies were
      heterogeneous in study population, diabetes mellitus diagnostic criteria, and
      outcome ascertainment. CONCLUSION: Patients with colorectal cancer who have
      diabetes mellitus are at greater risk for all-cause and cancer-specific mortality
      and have worse disease-free survival than those who do not have diabetes
      mellitus. Studies are warranted to determine whether the proper treatment could
      attenuate the excess mortality among patients with colorectal cancer who have
      diabetes mellitus.

PMID- 24105009
TI  - The revised faecal incontinence scale: a critical appraisal.

PMID- 24105010
TI  - The authors reply.

PMID- 24105013
TI  - Building social currency with foreskin cuts: a coping mechanism of Papua New
      Guinea health workers and the implications for new programmes.
AB  - BACKGROUND: Recent research as part of a multi-disciplinary investigation on the
      acceptability and impact of male circumcision for HIV prevention in Papua New
      Guinea (PNG) has shown that health workers (HWs) undertake unauthorized forms of
      penile cutting practices in public health facilities or in community settings, at
      times within a traditional context. Participation in these activities shares
      common features with coping mechanisms, strategies used by HWs to alleviate the
      burden of unsatisfactory living and working conditions. Coping mechanisms,
      however, are typically described as motivated by economic advantage, but in PNG
      evidence exists that the behaviours of HWs are also influenced by opportunities
      for social capital. METHODS: Twenty-five in-depth interviews (IDIs) were
      completed with a variety of HWs from 2009 until 2011 and were triangulated with
      findings from 45 focus group discussions and 82 IDIs completed with community
      members as part of a wider qualitative study. Thematic analysis examined HW
      participation in unauthorized penile cutting services. RESULTS: The emergence of
      unauthorized practices as a coping mechanism in PNG is compelled by mutual
      obligations and social capital arising from community recognition and
      satisfaction of moral, professional and cultural obligations. Using the example
      of unauthorized penile cutting practices amongst HWs in PNG, the research shows
      that although economic gains are not explicitly derived, evidence exists that
      they meet other community and socio cultural responsibilities forming a social
      currency within local traditional economies. CONCLUSIONS: Coping mechanisms
      create an opportunity to extend the boundaries of a health system at the
      discretion of the HW. Fragile health systems create opportunities for coping
      mechanisms to become institutionalized, pre-empting appropriate policy
      development or regulation in the introduction of new programmes. In order to
      ensure the success of new programmes, the existence of such practices and their
      potential implications must be addressed within programme design, and in
      implementation and regulation.

PMID- 24105014
TI  - Laparoscopic cholecystectomy in a patient with situs inversus totalis: case
      report with review of literature.
AB  - Situs inversus totalis is a rare autosomal recessive disorder which can cause
      diagnostic confusion in a lot of clinical conditions including calculous
      cholecystitis due to the reversed anatomical positions of abdominal viscera.
      Laparoscopic cholecystectomy is much more challenging in the presence of this
      disorder due to loss of usual orientation. We present a case of a 43-year-old
      woman who was diagnosed at our centre to have calculous cholecystitis in the
      presence of situs inversus totalis. Laparoscopic cholecystectomy was performed
      safely after adjustment of the positions of the team inside the operative theatre
      and of the port sites. The patient tolerated the operation very well and was
      discharged home after 24h. On follow-up visit the patient was doing very well and
      completely free of symptoms. 

PMID- 24105015
TI  - From multidisciplinary to personalized treatment of colorectal liver metastases:
      4 reasons to consider RAS.

PMID- 24105016
TI  - Examining risk factor goal attainment and adherence to treatment among US heart
      failure patients: the National Health and Nutrition Examination Survey 2007-2010.
AB  - PURPOSE: Data are limited regarding the adequacy of risk factor control and
      adherence to recommended therapies among adults with heart failure (HF). We
      evaluated the adequacy of risk factor control and adherence to recommended
      pharmacologic therapies among non-institutionalized US adults with HF. METHODS:
      We examined data from US adults aged 18 years and older with a self-reported
      history of HF from the US National Health and Nutrition Examination Survey 2007
      2008 and 2009-2010. We estimated the proportions of subjects who reported
      recommended lifestyle modification and medications and were at target levels of
      blood pressure, low-density lipoprotein cholesterol (LDL-C), and hemoglobin A1c.
      RESULTS: Among 371 subjects with HF in our study, 73.7 % were non-smokers, while
      only 69.1, 51.9, and 56.2 % were at goal for blood pressure, LDL-C, and
      hemoglobin A1c (if diabetic), respectively; only 9.0 % were at goal for all
      measures. The proportions of non-smokers were lower in males (p < 0.01) and
      lowest in non-Hispanic blacks (p < 0.01). Subjects with less than a high school
      education (p < 0.05) were least likely to be at recommended blood pressure
      levels. The proportions exercising moderately, with recommended alcohol and
      sodium intakes, and with a normal body mass index were 8.3, 41.4, 28.9, and 17.5
      %, respectively. 83.3 % of HF patients were taking only one of the recommended
      four classes of drugs [beta-blockers, angiotensin converting enzyme
      inhibitors/angiotensin receptor blockers (ACEIs/ARBs), diuretics, and digoxin];
      only 50.1 % were additionally on a lipid-lowering agent. CONCLUSION: We observed
      a significant gap between adherence and control of HF risk factors and treatment
      among non-institutionalized US adults.

PMID- 24105017
TI  - Effects of N-acetylcysteine on the cardiac remodeling biomarkers and major
      adverse events following acute myocardial infarction: a randomized clinical
      trial.
AB  - AIMS: The aims of this study were to evaluate the effects of N-acetylcysteine
      (NAC) on cardiac remodeling and major adverse events following acute myocardial
      infarction (AMI). METHODS: In a prospective, double-blind, randomized clinical
      trial, the effect of NAC on the serum levels of cardiac biomarkers was compared
      with that of placebo in 98 patients with AMI. Also, the patients were followed up
      for a 1-year period for major adverse cardiac events (MACE), including the
      occurrence of recurrent myocardial infarction, death, and need for target vessel
      revascularization. RESULTS: In patients who received NAC, the serum levels of
      matrix metalloproteinase (MMP)-9 and MMP-2 after 72 h were significantly lower
      than those in the placebo group (p = 0.014 and p = 0.045, respectively). The
      length of hospitalization in patients who received NAC was significantly shorter
      than that in the placebo group (p = 0.024). With respect to MACE, there was a
      significant difference between those who received NAC (14 %) and those patients
      on placebo (25 %) (p = 0.024). Re-infarction took place in 4 % of patients in the
      NAC group as compared with 16.7 % in patients who received placebo (p = 0.007).
      CONCLUSION: NAC can be beneficial in preventing early remodeling by reducing the
      level of MMP-2 and MMP-9. Moreover, NAC decreased the length of hospital stays in
      patients after AMI. By decreasing MACE, NAC could possibly be introduced as a
      'magic bullet' in the pharmacotherapy of patients with AMI. Further studies are
      needed to elucidate NAC's role in this population.

PMID- 24105018
TI  - New drug avenues for cardioprotection in patients with acute myocardial
      infarction.

PMID- 24105020
TI  - Is posterior fixation alone effective to prevent the late kyphosis after T-L
      fracture?
AB  - INTRODUCTION: The posterior transpedicular fixation technique is a standard
      procedure for stabilizing the injured thoracolumbar spine but the long-term
      results of this approach are controversial. Clear guidelines are missing and the
      literature shows complete disagreement regarding indications, approaches,
      surgical techniques, and type of fixation. MATERIAL AND METHOD: The objective of
      this study is to investigate if the surgical treatment by posterior approach
      alone is always enough to prevent the late kyphotic deformity through the
      retrospective analysis of 219 patients affected with a thoracolumbar injury.
      Follow-up examinations included radiographic measurements of the sagittal index
      (SI) and the sagittal plane kyphosis (SPK). RESULT: Results show that, at the
      follow-up, the SI remains almost stable after the surgical correction, while the
      SPK (which describes the eventual injury of the affected intervertebral disc)
      decreases indicating a progressive regional kyphotic deformity. Thus, in some
      cases posterior fixation alone is not sufficient for long-term spinal
      stabilization and often can be not effective to prevent the late kyphotic
      deformity.

PMID- 24105019
TI  - The transpedicular approach for the study of intervertebral disc regeneration
      strategies: in vivo characterization.
AB  - PURPOSE: To characterize in vivo the transpedicular approach (TA) as an
      alternative route to study intervertebral disc (IVD) regeneration strategies in a
      sheep model. METHODS: 48 IVD of 12 sheep were used. TA was performed under
      fluoroscopy, followed by nucleotomy (2-mm shaver resector). A polyurethane
      scaffold was used to repair the end-plate. X-ray and MRI images were acquired pre
      , intra- and post-operatively (1, 3, 6 months). Complications were recorded.
      RESULTS: TA was feasible in all animals; nucleus pulposus (NP) from L1 to L5 was
      accessible. Nucleotomy followed by end-plate repair was achieved. Loss of NP
      signal intensity was shown in MRI images of the nucleotomy group. CONCLUSIONS: TA
      is feasible in vivo, repeatable after only a short learning period and safely
      performed without significant morbidity. This animal model allows the study of
      IVD degeneration physiopathology and investigation of IVD regeneration techniques
      in vivo.

PMID- 24105021
TI  - A SNP in the 5'UTR of GDF5 is associated with susceptibility to symptomatic
      lumbar disc herniation in the Chinese Han population.
AB  - PURPOSE: The aim of the present study is to assess whether the single nucleotide
      polymorphism in the GDF5 (+104T/C; rs143383) is associated with the symptomatic
      lumbar disc herniation in the Chinese Han population and the identification of
      the mechanisms of its action. METHODS: This study consisted of 231 patients with
      symptomatic lumbar disc herniation as the case group and 370 patients who had a
      lifetime lack of symptoms as the control group. PCR products were genotyped.
      Thirty-eight disc specimens derived from the cases were analyzed by
      immunohistochemical staining. The stain intensity of immunohistochemistry was
      quantified using a computerized image analysis system. RESULTS: Significant
      differences in genotypic and allelic frequencies were found between case group
      and control group (TT genotype P < 0.001; CC genotype P = 0.002; T allele P <
      0.001). The T allele was more frequent in the case group regardless of gender
      (Female P = 0.018; Male P < 0.001). Significant differences were found in the
      genotype frequencies when stratified by gender except the comparison between the
      CC genotype and other genotypes combined among the female samples (P > 0.05). A
      semi-quantification of collagen protein in the nucleus pulposus showed that the
      average collagen protein content in TC group was higher than in TT group (P <
      0.05). CONCLUSION: Our results suggested that the GDF5 polymorphism is associated
      with a susceptibility to symptomatic lumbar disc herniation in the Chinese Han
      population and type II collagen in the nucleus pulposus may be a key factor in
      susceptibility to symptomatic lumbar disc herniation.

PMID- 24105022
TI  - Decreased Kruppel-like factor 4 (KLF4) expression may correlate with poor
      survival in gastric adenocarcinoma.
AB  - Kruppel-like factors (KLFs) play either anti- or pro-proliferation roles in
      different human cancers. Here, we investigated the expression of KLF4 in gastric
      cancers and its correlation with clinicopathological parameters and overall
      survival. KLF4 expression was measured in 118 surgical specimens by
      immunohistochemical microarray assay. No association of cytoplasmic KLF4
      expression with gender, TNM status, stage, survival, and pathological type was
      found. Using Kaplan-Meier analysis, significantly higher overall survival rate
      was observed in patients with high cytoplasmic KLF4 expression compared to low
      cytoplasmic KLF4 expression. Univariate analysis revealed that cytoplasmic KLF4
      expression, grade, histological type, lymph node metastasis, and stages were
      correlated to longer overall survival. Our results suggest that KLF4 may play an
      anti-oncogenic role in gastric tumorigenesis. 

PMID- 24105023
TI  - Hemophagocytic lymphohistiocytosis (HLH): a review of literature.
AB  - Hemophagocytic lymphohistiocytosis (HLH) is a rare disease in children and an
      exceptionally rare occurrence in adults. It is categorized broadly into primary
      (familial) or the secondary types; the latter being associated most commonly with
      an underlying malignancy. HLH carries a high rate of mortality, and the treatment
      itself is associated with significant morbidity and risk of mortality. A high
      degree of suspicion for the diagnosis, early treatment and aggressive supportive
      care is critical for management. We present a comprehensive review of literature
      describing the clinical features, diagnosis, management and outcome of HLH. 

PMID- 24105024
TI  - Enhanced biofuel production through coupled acetic acid and xylose consumption by
      engineered yeast.
AB  - The anticipation for substituting conventional fossil fuels with cellulosic
      biofuels is growing in the face of increasing demand for energy and rising
      concerns of greenhouse gas emissions. However, commercial production of
      cellulosic biofuel has been hampered by inefficient fermentation of xylose and
      the toxicity of acetic acid, which constitute substantial portions of cellulosic
      biomass. Here we use a redox balancing strategy to enable efficient xylose
      fermentation and simultaneous in situ detoxification of cellulosic feedstocks. By
      combining a nicotinamide adenine dinucleotide (NADH)-consuming acetate
      consumption pathway and an NADH-producing xylose utilization pathway, engineered
      yeast converts cellulosic sugars and toxic levels of acetate together into
      ethanol under anaerobic conditions. The results demonstrate a breakthrough in
      making efficient use of carbon compounds in cellulosic biomass and present an
      innovative strategy for metabolic engineering whereby an undesirable redox state
      can be exploited to drive desirable metabolic reactions, even improving
      productivity and yield. 

PMID- 24105025
TI  - Mineralization of DNA into nanoparticles of hydroxyapatite.
AB  - Encapsulation of DNA into hydroxyapatite (HAp) has been investigated using a
      rational approach that involves computer simulation and experimental techniques.
      The temporal evolution of the radial distribution functions derived from
      atomistic molecular dynamics simulations of Ca(2+), PO4(3-) and OH(-)-containing
      aqueous solutions in the presence and absence of B-DNA has been used to conclude
      that the backbone of the double helix acts as a template for HAp growth. More
      specifically, results reveal the formation of calcium phosphate clusters at the
      first stages of the simulations, which subsequently re-organize to nucleate HAp.
      This effect is produced in the absence and, especially, presence, of DNA
      indicating that the biomolecules do not inhibit but even promote mineral growth.
      Furthermore, computer simulations suggest that the diffusion of the OH(-) anions
      through the inorganic solution is the limiting step for the nucleation of the
      biomineral. Nanocapsules and crystalline nanorods of HAp containing DNA molecules
      inside have been prepared by mixing solutions containing Ca(2+) and PO4(3-) ions
      with fish sperm DNA at high pH. The dimensions and morphology of such
      nanostructures have been examined by transmission electron microscopy, while the
      characterization of the biomineral has been focused on the identification of DNA
      inside HAp using infrared, X-ray photoelectron and UV-vis spectroscopies, as well
      as gel electrophoresis. The biominerals reported in this work are important for
      biomedical applications requiring the protection of DNA from aggressive
      environmental conditions. 

PMID- 24105026
TI  - Neuroprotective effects of farnesene against hydrogen peroxide-induced
      neurotoxicity in vitro.
AB  - Oxidative stress is highly damaging to cellular macromolecules and is also
      considered a main cause of the loss and impairment of neurons in several
      neurodegenerative disorders. Recent reports indicate that farnesene (FNS), an
      acyclic sesquiterpene, has antioxidant properties. However, little is known about
      the effects of FNS on oxidative stress-induced neurotoxicity. We used hydrogen
      peroxide (H2O2) exposure for 6 h to model oxidative stress. Therefore, this
      experimental design allowed us to explore the neuroprotective potential of
      different FNS isomers (alpha-FNS and beta-FNS) and their mixture (Mix-FNS) in
      H2O2-induced toxicity in newborn rat cerebral cortex cell cultures for the first
      time. For this aim, both MTT and lactate dehydrogenase assays were carried out to
      evaluate cell viability. Total antioxidant capacity (TAC) and total oxidative
      stress (TOS) parameters were used to assess oxidative alterations. In addition to
      determining of 8-hydroxy-2-deoxyguanosine (8-OH-dG) levels in vitro, the comet
      assay was also performed for measuring the resistance of neuronal DNA to H2O2
      induced challenge. Our results showed that survival and TAC levels of the cells
      decreased, while TOS, 8-OH-dG levels and the mean values of the total scores of
      cells showing DNA damage (comet assay) increased in the group treated with H2O2
      alone. But pretreatment of FNS suppressed the cytotoxicity, genotoxicity and
      oxidative stress, which were increased by H2O2 in clear type of isomers and
      applied concentration-dependent manners. The order of antioxidant effectiveness
      for modulating H2O2-induced oxidative stress-based neurotoxicity and genotoxicity
      is as beta-FNS > Mix-FNS > alpha-FNS. 

PMID- 24105027
TI  - Peculiar magnetism of BiFeO3 nanoparticles with size approaching the period of
      the spiral spin structure.
AB  - Size effect of multiferroics is important for its potential applications in new
      type miniaturized multifunctional devices and thus has been widely studied.
      However, is there special size effect in the materials with spiral modulated spin
      structure (such as BiFeO3)? It is still an issue to be investigated. In this
      report, structural, magnetic and magnetoelectric coupling properties are
      investigated for sol-gel prepared BiFeO3 nanoparticles with various sizes. It is
      found that a structural anomaly arises for the particles with size close to the
      62 nm period of the spiral modulated spin structure, which induces an obviously
      increased ferromagnetism. In addition, large magnetoelectric coupling effect is
      observed in 62 nm BiFeO3 nanoparticles. Our result provides another insight into
      the size effect of BiFeO3, and also a clue to the magnetic structure at
      nanoscale.

PMID- 24105028
TI  - Parallel synthesis and splicing redirection activity of cell-penetrating peptide
      conjugate libraries of a PNA cargo.
AB  - A novel method for the parallel synthesis of peptide-biocargo conjugates was
      developed that utilizes affinity purification for fast isolation of the
      conjugates in order to avoid time consuming HPLC purification. The methodology
      was applied to create two libraries of cell-penetrating peptide (CPP)-PNA705
      conjugates from parallel-synthesized peptide libraries. The conjugates were
      tested for their ability to induce splicing redirection in HeLa pLuc705 cells.
      The results demonstrate how the novel methodology can be applied for screening
      purposes in order to find suitable CPP-biocargo combinations and further
      optimization of CPPs. 

PMID- 24105029
TI  - DNA/long peptide vaccination against conserved regions of SIV induces partial
      protection against SIVmac251 challenge.
AB  - OBJECTIVES: We recently developed a HIVconsv vaccine strategy, consisting of
      combined conserved regions of HIV-1, to adequately cover viral diversity. To
      evaluate efficacy in nonhuman primates, an equivalent SIV-derived immunogen
      SIVconsv was designed and delivered as plasmid DNA or synthetic long peptides.
      DESIGN: Rhesus macaques lacking protective MHC class I alleles Mamu-A*001 : 01,
      B*008 : 01, B*017 : 01 were immunized with either SIVconsv synthetic long
      peptides (S) alone or in combination with plasmid DNA encoding the same conserved
      regions (D) using SSS or DDSS regimens. METHODS: The SIVconsv synthetic long
      peptide vaccine consisted of 46 approximately 30-amino acid-long peptides
      emulsified in Montanide ISA-720 and adjuvanted with pegylated type I interferon
      and imiquimod. RESULTS: Both SSS and DDSS regimens generated high frequencies of
      SIV-specific IFN-gamma-producing cells comparable with reported adenoviral vector
      systems. Strong polyfunctional CD4+ T-cell and modest CD8+ T-cell responses were
      generated, which were of central memory T-cell phenotype. Furthermore, SIVconsv
      specific antibody responses were induced capable of recognizing the Env
      glycoprotein. Eight weeks after the last immunization, control and SIVconsv
      vaccinated animals were challenged intrarectally with 10 MID50 of pathogenic
      SIVmac251. Two out of six animals in the DDSS group were protected against
      infection, while all 14 animals in the SSS and two control groups were infected.
      Vaccine induced SIV-specific IgG responses in mucosal washes prechallenge were
      highest in the two protected animals. CONCLUSION: This study demonstrates that
      vaccine-elicited responses towards conserved regions can afford partial
      protection against a high-dose intrarectal SIVmac251 challenge.

PMID- 24105031
TI  - Supplementation effect with slow-release urea in feed blocks for Thai beef cattle
      -nitrogen utilization, blood biochemistry, and hematology.
AB  - Four Thai male native beef cattle, initial body weight (BW) of 100 +/- 3.0 kg
      were randomly assigned in a 4 * 4 Latin square design to receive four dietary
      treatments with inclusion of urea calcium sulphate mixture (U-cas) in feed block
      (FB) at 0, 120, 150, and 180 g/kg dry matter (DM). Total intakes were increased
      with the increasing level of U-cas supplementation in FB and the result obtained
      the highest when supplementation of U-cas in FB at 180, followed by 150, 120, and
      0 g/kg DM, respectively. Moreover, supplementation of U-cas in FB at 180 g/kg DM
      could reduce total N excretion (4.1 g/day), as compared to others treatments,
      while N retention and proportion of N retention to N intake were increased up to
      6.9 g/day and 14.9 %, respectively. On the other hand, the blood biochemistry and
      hematological parameters were not different among treatments except concentration
      of plasma urea N, plasma glucose, and total blood protein were improved
      especially with U-cas supplementation at 180 g/kg DM in FB. In conclusion,
      supplementation of U-cas at 180 g/kg in FB improved feed intake, N utilization,
      and blood biochemistry in Thai native beef cattle fed on rice straw.

PMID- 24105030
TI  - Cause-specific mortality among HIV-infected individuals, by CD4(+) cell count at
      HAART initiation, compared with HIV-uninfected individuals.
AB  - OBJECTIVES: To compare the proportion, timing and hazards of non-AIDS death and
      AIDS death among men and women who initiated HAART at different CD4 cell counts
      to mortality risks of HIV-uninfected persons with similar risk factors. DESIGN:
      Prospective cohort studies. METHODS: We used parametric mixture models to compare
      proportions of AIDS and non-AIDS mortality and ages at death, and multivariable
      Cox models to compare cause-specific hazards of mortality, across levels of CD4
      cell count at HAART initiation (<=200 cells/MUl: 'late', 201-350 cells/MUl:
      'intermediate', >350 cells/MUl: 'early') and with HIV-uninfected individuals from
      the Multicenter AIDS Cohort Study and the Women's Interagency HIV Study. We used
      multiple imputation methods to address lead-time bias in sensitivity analysis.
      RESULTS: Earlier initiators were more likely to die of non-AIDS causes (early:
      78%, intermediate: 74%, late: 49%), and at older ages (median years 72, 69, 66),
      relative to later initiators. Estimated median ages at non-AIDS death for each
      CD4 cell count category were lower than that estimated for the HIV-uninfected
      group (75 years). In multivariable analysis, non-AIDS death hazard ratios
      relative to early initiators were 2.15 for late initiators (P < 0.01) and 1.66
      for intermediate initiators (P = 0.01); AIDS death hazard ratios were 3.26 for
      late initiators (P < 0.01) and 1.20 for intermediate initiators (P = 0.28).
      Strikingly, the adjusted hazards for non-AIDS death among HIV-uninfected
      individuals and early initiators were nearly identical (hazard ratio 1.01).
      Inferences were unchanged after adjustment for lead-time bias. CONCLUSION:
      Results suggest the possibility of reducing the risk of non-AIDS mortality among
      HIV-infected individuals to approximate that faced by comparable HIV-uninfected
      individuals.

PMID- 24105032
TI  - Technical note: 3D representation and analysis of enthesis morphology.
AB  - This comparison of methods for assessing the development of muscle insertion
      sites, or entheses, suggests that three-dimensional (3D) quantification of
      enthesis morphology can produce a picture of habitual muscle use patterns in a
      past population that is similar to one produced by ordinal scores for describing
      enthesis morphology. Upper limb skeletal elements (humeri, radii, and ulnae) from
      a sample of 24 middle-aged adult males from the Pottery Mound site in New Mexico
      were analyzed for both fibrous and fibrocartilaginous enthesis development with
      three different methods: ordinal scores, two-dimensional (2D) area measurements,
      and 3D surface areas. The methods were compared using tests for asymmetry and
      correlations among variables in each quantitative data set. 2D representations of
      enthesis area did not agree as closely as ordinal scores and 3D surface areas did
      regarding which entheses were significantly asymmetrical. There was significant
      correlation between 3D and 2D data, but correlation coefficients were not
      consistently high. Intraobserver error was also assessed for the 3D method.
      Cronbach's alpha values fell between 0.68 and 0.73, and error rates for all
      entheses fell between 10% and 15%. Marginally acceptable intraobserver error and
      the analytic versatility of 3D images encourage further investigation of using 3D
      scanning technology for quantifying enthesis development.

PMID- 24105033
TI  - Clinical effectiveness of seasonal influenza vaccine among adult cancer patients.
AB  - BACKGROUND: Patients with cancer are at increased risk of developing
      complications of influenza. In this study, the authors assessed the effectiveness
      of influenza vaccination among cancer patients. METHODS: A prospective,
      noninterventional cohort study was conducted during the 2010 to 2011 influenza
      season. The cohort included adult cancer patients with solid malignancies who
      were receiving chemotherapy and hematologic patients who had active disease.
      Patients who died between October and November 2010 (N = 43) were excluded. A
      comparison was made between patients who received the 2011 seasonal influenza
      vaccine with those who did not. The primary outcome was a composite of
      hospitalizations for fever or acute respiratory infections, pneumonia, and/or
      infection-related chemotherapy interruptions. All-cause mortality was a secondary
      outcome. A propensity-matched analysis was conducted based on the propensity for
      vaccination. RESULTS: Of 806 patients who were included, 387 (48%) were
      vaccinated. Factors that were associated independently with vaccination included
      past influenza vaccination, past pneumococcal vaccination, >6 months since cancer
      diagnosis, country of birth, and cancer type/status. The primary outcome occurred
      in 111 of 387 (28.7%) vaccinated patients versus 112 of 419 (26.7%) unvaccinated
      patients (P = .54). No association was observed between vaccination and the
      primary outcome in a propensity-matched analysis (N = 436) or during peak
      influenza activity. The mortality rate was 11.9% (46 of 387 patients) in
      vaccinated patients versus 19.1% (80 of 419 patients) in unvaccinated patients (P
      = .005). Vaccination retained a significant association with mortality on
      multivariable analysis (odds ratio, 2.31; 95% confidence interval, 1.4-3.79) and
      in a propensity-matched analysis (odds ratio, 2.39; 95% confidence interval, 1.32
      4.32). CONCLUSIONS: Influenza vaccination was associated with lower mortality
      among cancer patients, although an association with infection-related
      complications could not be demonstrated. The current results support efforts to
      promote influenza vaccination in patients with cancer.

PMID- 24105035
TI  - Impact of Pt additives on the surface reactions between SnO2, water vapour, CO
      and H2; an operando investigation.
AB  - The impact of Pt doping on the surface reactions between tin dioxide, water
      vapour, CO and H2 was investigated by a combination of simultaneously performed
      operando DRIFT (Diffuse Reflectance Infrared Fourier Transform) spectroscopy, DC
      resistance measurements and analysis of the reaction products by using a MS (Mass
      Spectrometer). Both undoped and Pt doped tin dioxide sensors were exposed to
      different test gases in synthetic air or in N2 backgrounds. The approach made it
      possible to identify the differences between the two materials with respect to
      their surface chemistry and their impact on the gas sensing performance. The main
      finding is that the presence of Pt changes the reaction partners' nature for
      water vapour and H2 on the one hand, and CO on the other hand when the sensors
      are operated in air. In this way the cross interference effect of humidity, which
      is responsible for the loss of CO sensing performance for the sensors based on
      undoped SnO2, is reversed. 

PMID- 24105034
TI  - Oryza sativa polyamine oxidase 1 back-converts tetraamines, spermine and
      thermospermine, to spermidine.
AB  - KEY MESSAGE: Oryza sativa polyamine oxidase 1 back-converts spermine (or
      thermospermine) to spermidine. Considering the previous work, major path of
      polyamine catabolism in rice plant is suggestive to be back-conversion but not
      terminal catabolism. Rice (Oryza sativa) contains seven genes encoding polyamine
      oxidases (PAOs), termed OsPAO1 to OsPAO7, based on their chromosomal number and
      gene ID number. We previously showed that three of these members, OsPAO3, OsPAO4
      and OsPAO5, are abundantly expressed, that their products localize to peroxisomes
      and that they catalyze the polyamine back-conversion reaction. Here, we have
      focused on OsPAO1. The OsPAO1 gene product shares a high level of identity with
      those of Arabidopsis PAO5 and Brassica juncea PAO. Expression of OsPAO1 appears
      to be quite low under physiological conditions, but is markedly induced in rice
      roots by spermine (Spm) or T-Spm treatment. Consistent with the above finding,
      the recombinant OsPAO1 prefers T-Spm as a substrate at pH 6.0 and Spm at pH 8.5
      and, in both cases, back-converts these tetraamines to spermidine, but not to
      putrescine. OsPAO1 localizes to the cytoplasm of onion epidermal cells. Differing
      in subcellular localization, four out of seven rice PAOs, OsPAO1, OsPAO3, OsPAO4
      and OsPAO5, catalyze back-conversion reactions of PAs. Based on the results, we
      discuss the catabolic path(s) of PAs in rice plant.

PMID- 24105037
TI  - [Ability of smelling is reduced reversibly by acute smoking and permanently by
      chronic smoking].
AB  - BACKGROUND: Whether smoking affects the sense of smell is in debate. To exclude a
      bias by presbyosmia, we analyzed the influence of acute and chronic smoking on
      the ability to smell in young adults. MATERIAL AND METHODS: 40 smokers (23 women,
      17 men) aged between 18-34 years were included. They smoked in average 19.6
      cigarettes per day and had an average of 7.96 pack years (minimum: 2.5; maximum:
      25). The sense of smell was evaluated using the Sniffin' sticks(c) olfactory test
      battery in 215 min 5 times. The impact of a 2 h controlled abstinence time and
      subsequent smoking of a cigarette were measured. 43 never smokers were tested as
      control group. RESULTS: Smoking had a 2-fold impact on the sense of smell: there
      was a reversible impairment after acute smoking and a permanent reduction of
      olfaction in relation to the pack years. In summary, the young smokers remained
      normosmic, although they showed significantly worse test results compared to the
      group of never smokers. The olfactory capacity of different groups of smokers
      differed up to maximum of 4.5 TDI points (sum of olfactory threshold-,
      discrimination- and identification-score). CONCLUSIONS: The damage caused by
      smoking seems to be settled in the border area between norm- and hyposmia. In
      case of an expert opinion the patient should be asked for the pack years and
      should keep 2 h controlled smoking abstinence prior to olfactory testing.

PMID- 24105038
TI  - [A phonation-related phase-model of the velopharyngeal closure based on high
      resolution manometry].
AB  - OBJECTIVE: The production of many speech sounds requires a complete
      velopharyngeal closure (VPC) caused by muscular contractions and approximation of
      the pharyngeal walls. The contraction pressure of the muscles involved needs to
      be high enough to withstand phonation pressure. It is postulated that sustained
      phonation consists of 3 velopharyngeal phases: an initial pressure buildup, a
      steady state and a final pressure decrease. To test this hypothesis, phonation
      induced pressure changes in the VPC were measured in healthy participants.
      MATERIAL AND METHODS: High resolution manometry was performed on 8 participants
      during the sustained phonation of the vowel / i:/. Individual pressure curves
      have been compared in order to verify the postulated model and intraindividual
      reproducibility has been tested. RESULTS: The intraindividual pressure curves
      were found to be reproducible, but an interindividual variation was observed. An
      initial pressure increase was detected in all participants at the onset of
      phonation, followed by a stable phase during sustained phonation. At the offset
      the pressures returned to the initial value during rest. CONCLUSIONS: The
      postulated model was verified in all participants. An initial phase, a stable
      phase and a terminal phase could be differentiated. Further classifications can
      be made regarding the on- and offset of phonation allowing for a more detailed
      characterization of the VPC. Further studies should evaluate if this model is
      useful to describe changes in the VPC pressure profile of patients affected by
      rhinophonia.

PMID- 24105039
TI  - [Adoption of the new patient rights law: more paperwork hassles in the clinic and
      general practice].

PMID- 24105040
TI  - [Letter to the editor on the publication by H. Rudert: Report on the iatrogenic
      injury of the internal carotid artery at adenoidectomy In: Laryngo-Rhino-Otology
      2013; 92: 256-257].

PMID- 24105041
TI  - [Not Available].

PMID- 24105042
TI  - [Skull base trauma in the otorhinolaryngologic specialty].

PMID- 24105043
TI  - [Optimizing diagnosis, medical management and planning of surgery - optimizing
      diagnosis - II].

PMID- 24105045
TI  - Management and outcome of high-grade multicentric gliomas: a contemporary single
      institution series and review of the literature.
AB  - BACKGROUND: Multicentric malignant gliomas are well-separated tumours in
      different lobes or hemispheres, without anatomical continuity between lesions.
      The purpose of this study was to explore the clinical features, the pathology and
      the outcome according to the management strategies in a consecutive series of
      patients treated at a single institution. In addition, an analysis of the
      existing literature is presented. METHODS: For the institutional analysis, a
      retrospective review of all patients who underwent treatment for multicentric
      gliomas in the last 7 years was performed. For the analysis of the literature, a
      MEDLINE search with no date limitations was accomplished for surgical treatment
      of multicentric malignant gliomas. RESULTS: Two hundred and thirty-nine patients
      with glioma were treated in our department. Eighteen patients (7.5 %) with a mean
      age of 64 years (age range, 37-78 years) presented multicentric malignant
      gliomas. Thirteen patients (72 %) underwent surgical resection of at least one
      lesion that was followed by adjuvant treatment in all but one case. Five patients
      (28 %) underwent stereotactic biopsy and thereafter received chemotherapy. A
      survival advantage was associated with resection of at least one lesion followed
      by adjuvant treatment (median overall survival 12 months) compared with 4 months
      for stereotactic biopsy followed by chemotherapy. Similar results were obtained
      from the review of the literature. CONCLUSIONS: Resection of at least one lesion
      seems to play a significant role in the management of selected patients with
      multicentric malignant gliomas. Multi-institutional studies on larger series are
      warranted to define how aggressively the patients with malignant multicentric
      gliomas should be treated.

PMID- 24105046
TI  - Venous air embolism (VAE) associated with stereotactic biopsies.
AB  - BACKGROUND: Venous air embolism (VAE) is a serious potential complication of
      neurosurgical procedures. Stereotactic biopsies can also cause VAE; therefore, we
      evaluated VAE patients to call attention to the risk of VAE associated with
      stereotactic biopsies. METHODS: In this report, symptomatic VAE was defined as
      paroxysmal coughing with associated symptoms. Air in the dural sinus, cortical
      vein and/or pterygoid plexus on postoperative computed tomography (CT) scans was
      considered to be a radiographic VAE. RESULTS: Three patients developed
      symptomatic VAE following 36 stereotactic biopsies, and the incidence of
      symptomatic VAE was 8.3 % (3/36). There were five patients with evidence of
      radiographic VAE on postoperative CT scans, with an incidence of 13.8 % (5/36). A
      high angle of the head seemed to be associated with VAE, allowing air to flow
      into the central venous system. CONCLUSIONS: The present report emphasizes that
      VAE should be recognized as an important adverse effect of stereotactic biopsies
      because VAE occasionally requires additional treatment and/or termination of
      surgery. Surgeons must be aware of the possibility of VAE, especially when it is
      necessary to position the patient's head at a high angle.

PMID- 24105047
TI  - Peroxiredoxin 3 is resistant to oxidation-induced apoptosis of Hep-3b cells.
AB  - OBJECTIVE: Although peroxiredoxin 3 (PRX3) was reported to be overexpressed in
      liver cancer, the precise function of PRX3 in the development and/or progression
      of liver cancer remained to be obscure. The present study was conducted to
      investigate the response of PRX3 to oxidative stress in hepatocellular carcinoma
      (HCC) cells. METHODS: After successful knockdown of PRX3 expression by small
      interfering RNA, we treated HCC cell lines Hep-3b and Hep-G2 with gradient
      concentrations of H2O2 and detected cell proliferation, apoptosis, and the level
      of reactive oxygen species (ROS) in the cells. RESULTS: After low-dose (5-20
      MUmol/l) H2O2 treatment, the ROS level was significantly higher in PRX3-knockdown
      Hep-3b cells than in controls. In addition, PRX3 down-regulation resulted in
      decreased proliferation, increased apoptosis, and increased caspase 3 activity of
      Hep-3b cells. We did not notice significant difference between PrxIII knockdown
      and control Hep-G2 cells in ROS level, cell viability or apoptosis. CONCLUSION:
      Our results suggest that PRX3 is an indispensable ROS scavenger that protects
      tumor cells against oxidative damage and subsequent apoptosis, which provides a
      clue that PRX3 may be involved in the chemotherapeutic resistance of liver
      cancer. The underlying mechanism for PRX3 function needs further investigation.

PMID- 24105048
TI  - Concurrent chemoradiotherapy with low-dose docetaxel inhibits the growth of DU
      145 prostate cancer xenografts.
AB  - INTRODUCTION: Concurrent chemoradiotherapy (CCRT) has been widely used during the
      past decades in clinical trials and has now become a common treatment option in
      many clinical settings. The present study was designed to evaluate the efficacy
      of combining radiation with low-dose docetaxel in DU-145 prostate cancer
      xenograft models. METHODS: Male BALB/c nude mice bearing human DU-145 prostate
      tumors were assigned to four treatment groups: (1) control, (2) docetaxel (10
      mg/kg/week, i.v., *3 weeks), (3) radiation (2 Gy, q.d. *5, *3 weeks), (4) CCRT
      (the combination of docetaxel and radiation). Treatment efficacy was determined
      by tumor volume and tumor regression measurements. The extent of apoptosis in
      tumors in response to treatments was assessed via terminal deoxynucleotidyl
      transferase-mediated nick-end labeling (TUNEL) assay. In addition,
      immunohistochemical staining of CD34 was done to quantify microvessel density in
      the tumors. RESULTS: Our in vivo studies using DU-145 xenograft models in nude
      mice showed that CCRT compared to either alone significantly inhibited tumor
      growth, and the percentages of tumor regression were 32.6, 44.2, and 68.6 % for
      docetaxel, radiation, and CCRT, respectively. Moreover, CCRT did not
      significantly affected mice weight as compared to docetaxel or radiation alone.
      TUNEL assays showed that significantly more apoptotic cells were induced in the
      tumors treated with CCRT than either treatment alone. Anti-CD34
      immunohistochemical staining indicated that CCRT significantly inhibited tumor
      angiogenesis. CONCLUSION: These findings suggest that CCRT with low-dose
      docetaxel inhibits the growth of DU-145 prostate cancer xenografts, by enhancing
      apoptosis and suppressing angiogenesis. Based on these preclinical findings, we
      suggest that CCRT for the treatment of prostate cancer deserves further
      development.

PMID- 24105049
TI  - [Multidisciplinary treatment strategy for gastric cancer with peritoneal
      metastasis].
AB  - As no treatment method has a sufficient level of evidence of success in the
      treatment of gastric cancer with peritoneal metastasis, there is an urgent need
      to develop a new treatment that takes into account the pathophysiology of the
      disease. A novel multidisciplinary treatment approach combining intraperitoneal
      (IP) paclitaxel (PTX), systemic chemotherapy, and gastrectomy is one of the
      promising treatment options. We designed a combination chemotherapy regimen of S
      1, weekly intravenous and IP PTX and determined the recommended dose in a phase I
      study. In the phase II study, the median survival time (MST) was 23.6 months. Out
      of 100 patients treated with this regimen, we performed gastrectomy on 62
      patients after disappearance or obvious shrinkage of the peritoneal metastasis,
      and the MST was 34.5 months. Currently, we are carrying out a phase III trial
      (PHOENIX-GC trial) comparing our IP regimen to S-1 plus CDDP.

PMID- 24105050
TI  - [Present status and future prospects of multi-disciplinary therapy for malignant
      gliomas].
AB  - The prognosis of malignant gliomas is poor. The 5-year survival rate of patients
      with glioblastomas is still less than 10%. It is difficult to cure this disease
      by a single treatment modality, and thus, the use of multi-disciplinary therapy
      mainly comprising surgery, radiotherapy, and chemotherapy is necessary. Malignant
      gliomas invade the adjacent brain tissue; however, it is well known that greater
      the extent of tumor resection better is the prognosis. Maximal resection is very
      important, and various procedures such as intraoperative navigation, evoked
      potential, photodynamic diagnosis, intraoperative magnetic resonance imaging
      (MRI), and awake surgery are performed to preserve speech and motor function in
      patients. According to a phase III trial by the European Organization for
      Research and Treatment for Cancer (EORTC), the standard therapy for glioblastomas
      is radiotherapy with concomitant administration of temozolomide; however, the
      median survival time is only 14.6 months. Multi-institutional, cooperative trials
      are necessary for the development of more effective and safe standard therapy.

PMID- 24105051
TI  - [Current situation and future prospects of radiotherapy for malignant gliomas].
AB  - Prognosis of malignant gliomas remains poor, although adjuvant radiotherapy
      increases survival time. To improve treatment outcomes, high-precision
      radiotherapy techniques such as three-dimensional conformal radiotherapy,
      stereotactic irradiation, intensity modulated radiotherapy, and charged particle
      radiotherapy have been developed for dose distribution optimization and dose
      escalation. Improvements in clinical outcomes with these new treatment strategies
      have been reported; however, the efficacy of these treatment strategies has not
      yet been verified in randomized trials. Further development of radiation delivery
      techniques, including boron neutron capture therapy, and ways of achieving more
      adequate target volume delineation using modern multimodality imaging technology
      are currently being intensively investigated to further improve patient outcomes.

PMID- 24105052
TI  - [Chemotherapy for malignant gliomas: an update].
AB  - Gliomas account for approximately 30% of all brain tumors and are thus the most
      common primary tumors of the central nervous system (CNS). Despite treatment with
      aggressive surgical resection, chemotherapy, and radiotherapy, high-grade (WHO
      grades III and IV) malignant gliomas, especially glioblastoma (GBM), the most
      common glioma in adults, kill patients within a median time span of a year after
      diagnosis. In Japan, alkylating agents such as 1-(4-amino-2-methyl-5-pyridiminyl)
      methyl-3-(2-chloroethyl)-3-nitrosourea (ACNU) and methyl-6-[3-(2-chloroethyl)-3
      nitrosoureido]-6-deoxy-alpha-D-glucopyranoside (MCNU) have been used to treat
      malignant gliomas for a long time; however, this treatment provides few clinical
      benefits. Temozolomide (TMZ), an oral alkylating agent, has been demonstrated to
      possess antitumor activity against malignant gliomas with minimal additional
      toxicity; furthermore, a previous study found that treatment with TMZ
      significantly prolonged median survival time. In 2006, TMZ was certified as the
      treatment agent for malignant gliomas by the National Ministry of Health and
      Welfare of Japan. It is now used as first-line therapy. However, its clinical
      outcomes depend on the O6-methylguanine-DNA methyltransferase (MGMT) status, and
      MGMT modification is one of the key factors to deriving greater clinical benefits
      in the future. Combination therapy with TMZ and other antitumor drugs, especially
      anti-vascular endothelial growth factor (VEGF) antibody (Avascin), has been
      aggressively investigated for treating gliomas. Some of these drugs have been
      studied in experimental animal models and advanced to clinical trials. These
      studies suggest that combination therapy with TMZ and other antitumor drugs might
      further improve the clinical outcome of malignant gliomas as compared to TMZ plus
      radiotherapy. Based on these data, the next step will be to carry out phase II to
      III clinical studies to improve treatment of malignant brain tumors further.

PMID- 24105053
TI  - [Multidisciplinary approach to management of patients with brain metastases].
AB  - The incidence of brain metastases has increased over time as a consequence of an
      increase in the overall survival of patients with various types of cancer and the
      improved detection by magnetic resonance imaging (MRI). In this study, the
      guidelines and evidence for the radiotherapeutic, surgical, and chemotherapeutic
      management of patients newly diagnosed with brain metastases have been reviewed.
      For patients with good prognosis (expected survival, >= 3 months) and single
      brain metastases (> 3-4 cm) in whom safe complete resection is possible, whole
      brain radiotherapy (WBRT) and surgery (level 1) should be considered. Another
      alternative is surgery and radiation boost to the resection cavity (level 3). For
      single brain metastases (< 3-4 cm) that are not resectable, WBRT and
      radiosurgery, or radiosurgery alone should be considered (level 1). For selected
      patients with a limited number of multiple brain metastases (all < 3-4 cm) and
      good prognosis (expected survival, >= 3 months), radiosurgery alone, WBRT and
      radiosurgery, or WBRT alone should be considered (level 1). However, data from
      recent clinical trials have shown that adjuvant WBRT after radiosurgery or
      surgery for a limited number of brain metastases reduces intracranial relapses
      and neurologic deaths but fails to improve the duration of functional
      independence and overall survival. Many clinical studies have reported the
      effectiveness of molecular targeted therapies for brain metastases. Gefitinib or
      erlotinib should be considered for the treatment of asymptomatic patients
      harboring activating epidermal growth factor receptor (EGFR) mutations. Lapatinib
      should also be considered for the treatment of patients with brain metastases
      from human epidermal growth factor receptor (HER)-2-overexpressing metastatic
      breast cancer. In Japan, the intravenous administration of bevacizumab is
      currently being used for the treatment of symptomatic radiation necrosis of the
      brain.

PMID- 24105054
TI  - [Examination of clinical presentation in terminal-phase lung cancer patients at a
      single palliative care unit].
AB  - OBJECTIVE: To study the clinical presentation of lung cancer patients at our
      palliative care unit (PCU). DESIGN: We examined the clinical presentation of lung
      cancer patients at our PCU and compared it with the clinical presentation of
      patients with malignant tumors besides those indicative of lung cancer. RESULTS:
      The PCU occupancy ratio of lung cancer patients to inpatients was 24%, which was
      dependent on the type of carcinoma. Lung cancer patients in need of oxygen
      inhalation and/or terminal sedation were more in number than those with other
      types of malignant tumors. On the other hand, few patients needed treatment.
      Dyspnea is the major reason for the terminal sedation of lung cancer patients.
      CONCLUSION: Severe dyspnea appeared to be the typical clinical presentation of
      terminal-phase lung cancer patients.

PMID- 24105055
TI  - [Neoadjuvant chemotherapy with combined S-1 plus weekly low-dose cisplatin
      followed by surgical resection for advanced gastric cancer].
AB  - We retrospectively examined patients with advanced gastric cancer who underwent
      gastrectomy following neoadjuvant chemotherapy (NAC) with S-1 plus weekly low
      dose cisplatin (CDDP). Between 2007 and 2009, 27 patients with advanced gastric
      cancer not amenable to curative surgery were enrolled. One course of NAC
      comprised S-1 (80 mg/m2/day) for 21 consecutive days and CDDP (20 mg/m2) on days
      1, 8, and 15; this was followed by a 2-week rest after the end of S-1
      administration. Grade 3 side effects were observed in 5 patients: 3 experienced
      neutropenia and 2 experienced digestive symptoms. The outpatient completion rate
      was 81.5% (22/27); there was no incidence of renal dysfunction. During pretherapy
      diagnosis, depth of invasion was classified as T4 in all cases. Postoperative
      pathologic results showed that the depth of invasion was T3 or lower in 4
      patients. In addition, the number of patients with N0 and M0 classification
      increased and downstaging was observed in 12 patients (44.4%). A comprehensive
      assessment revealed that a partial response (PR) was observed in 13 patients and
      stable disease (SD) was observed in 12 patients, resulting in a response rate of
      48.1%. The median survival time was 580 days, and the 1-year survival rate was
      72%. NAC with S-1 plus weekly low-dose CDDP can also be administered on an
      outpatient basis, and it is a potential regimen for the treatment of advanced
      gastric cancer associated with a poor prognosis.

PMID- 24105056
TI  - [Assessment of the vulnerable elders survey as a predictive test for elderly
      patients with advanced or metastatic gastric cancer treated with combined S-1 and
      docetaxel therapy].
AB  - Ten patients aged 75 years or more with advanced or metastatic gastric cancer
      were prescribed S-1 plus docetaxel (DOC) combination therapy. None of the
      patients showed complete response, but 2 showed partial response and 4 showed
      stable disease. Grade 3 or 4 toxicities occurred in 3 patients. Three patients
      with performance status (PS) 1 achieved partial response or stable disease and
      were free of Grade 3 or 4 toxicities, whereas the response and occurrence of
      adverse events in 7 patients with PS 2 varied widely. In these patients, an
      investigation of the relationship between response to treatment and the
      Vulnerable Elders Survey (VES-13) score showed that VES-13 scores were higher in
      the non-response group than in the other patients and in patients who experienced
      adverse events than in those who did not. These findings suggest that VES-13
      could be a useful screening tool for predicting response and the occurrence of
      adverse events in elderly patients undergoing combined S-1 plus DOC therapy for
      advanced or metastatic gastric cancer.

PMID- 24105057
TI  - [Continuation of chemotherapy with bevacizumab for advanced and recurrent
      colorectal cancer].
AB  - We evaluated the association between the number of treatment courses with the
      concomitant use of bevacizumab(BV) and the reasons for discontinuation of the
      regimen in patients who received FOLFOX with or without BV as first-line
      chemotherapy and FOLFIRI with or without BV as second-line chemotherapy for
      advanced and recurrent colorectal cancer. In first-line treatment, 12 (2-46) and
      10 (2-60) treatment courses were administered with and without BV, respectively,
      and this difference was not significant (p=0.60). In second-line treatment after
      first-line treatment with the concomitant use of BV, 11 (1-23) and 3 (1-12)
      treatment courses were administered with and without BV, respectively, and this
      difference was significant (p<0.01). Discontinuation due to adverse reactions was
      more frequent for first-line treatment (34.9%) than for second-line treatment
      (6.2%; p<0.01). The reasons for discontinuation due to adverse reactions during
      first-line treatment with BV were often associated with BV, and those during
      first-line treatment without BV were most often associated with peripheral
      neuropathy. Therefore, we conclude that early detection and prevention of adverse
      reactions are important in first-line treatment and that pharmacists as well
      should be involved in the monitoring and management of adverse reactions,
      although continued administration of BV even during second-line treatment after
      first-line treatment with BV is recommended.

PMID- 24105058
TI  - [Clinical experience with gemcitabine treatment for metastatic breast cancer].
AB  - It is difficult to cure recurrent or metastatic breast cancer (MBC). Therefore,
      it is important to continue treatment for MBC with maintenance of quality of life
      (QOL). Gemcitabine has been approved for MBC since February 2010. We administered
      gemcitabine to 39 patients with MBC between February 1, 2010 and March 31, 2012.
      Depending on the case, taxane or trastuzumab was added. Almost all patients had
      received prior chemotherapy or hormonal therapy. The median age of patients was
      61 years (range, 33-82 years), and the median number of previous treatment
      regimens was 3 (range, 0-6). The response rate was 15.4%, the disease control
      rate was 56.4%, and the clinical benefit rate was 33.3%. The main hematological
      adverse event was neutropenia, and the main non-hematological adverse event was
      fatigue. Neutropenia could be managed by reducing the gemcitabine dose or
      withdrawing treatment. Adverse events requiring hospitalization were not
      observed. These findings suggest that gemcitabine-based regimens are feasible in
      terms of efficacy and maintenance of QOL for patients with MBC.

PMID- 24105059
TI  - [Ice application for reducing pain associated with goserelin acetate injection].
AB  - We investigated the effectiveness of using an ice pack for reducing the pain
      associated with goserelin acetate injection. In this study, 39 patients with
      prostate cancer and 1 patient with breast cancer receiving hormonal therapy with
      goserelin acetate were enrolled. All patients completed a questionnaire regarding
      the use of ice application. We used the numerical rating scale (NRS) to assess
      the pain associated with injection. The NRS scores indicated that the pain was
      significantly less with ice application than with the usual method (p < 0.001).
      Further, ice application could decrease the duration of pain sensation. Ice
      application at the injection site is safe and effective for reducing pain.

PMID- 24105063
TI  - Quantum anomalous Hall effect and tunable topological states in 3d transition
      metals doped silicene.
AB  - Silicene is an intriguing 2D topological material which is closely analogous to
      graphene but with stronger spin orbit coupling effect and natural compatibility
      with current silicon-based electronics industry. Here we demonstrate that
      silicene decorated with certain 3d transition metals (Vanadium) can sustain a
      stable quantum anomalous Hall effect using both analytical model and first
      principles Wannier interpolation. We also predict the quantum valley Hall effect
      and electrically tunable topological states could be realized in certain
      transition metal doped silicene where the energy band inversion occurs. Our
      findings provide new scheme for the realization of quantum anomalous Hall effect
      and platform for electrically controllable topological states which are highly
      desirable for future nanoelectronics and spintronics application. 

PMID- 24105062
TI  - Chronic exposure of river sediments to environmentally relevant levels of
      tetracycline affects bacterial communities but not denitrification rates.
AB  - The effects of tetracycline (TC) at chronic sub-inhibitory exposure
      concentrations on benthic denitrification rates and bacterial communities were
      explored. River sediments were continuously exposed to different TC
      concentrations (0.5, 20 and 10,000 MUg L(-1)) for 2 weeks in flow-through
      reactors allowing denitrification and bacterial growth conditions. Bacterial
      communities were fingerprinted by Denaturing Gradient Gel Electrophoresis of 16S
      rRNA gene amplification products. Cultivable denitrifiers enriched from the
      sediment were tested for TC resistance (2-128 mg L(-1)). Denitrification rates
      were unaffected by exposure to TC, regardless of concentration. In contrast, the
      bacterial community composition changed significantly from sub-inhibitory (ng-MUg
      L(-1)) to therapeutic (mg L(-1)) exposure concentrations. Furthermore the
      cultivable denitrifiers showed a high TC sensitivity (<4 mg L(-1)). Maintenance
      of efficient benthic denitrification rates, even at the highest level of TC
      exposure most likely originated from an adaptation of the autochthonous bacterial
      community where dominant species become those that acquire, or already have
      resistance to antibiotics.

PMID- 24105064
TI  - Fast-pulsing NMR techniques for the detection of weak interactions: successful
      natural abundance probe of hydrogen bonds in peptides.
AB  - Structural investigations of peptides using NMR spectroscopy rarely include the
      detection of N-H...O=C and N-H...N hydrogen bonds, because the relevant
      heteronuclei have a low natural abundance while the small trans hydrogen bond
      scalar couplings reduce the sensitivity. Fast repetition NMR techniques combined
      with state of the art spectrometer specifications allowed the enhancement of the
      sensitivity for detection of hydrogen bonds at natural isotopic abundance.

PMID- 24105065
TI  - Heavy metal bioaccumulation in sediment, common reed, algae, and blood worm from
      the Shoor river, Iran.
AB  - Concentrations of 11 metals (cadmium, zinc, copper (Cu), vanadium (V), lead,
      magnesium (Mg), manganese, aluminum, iron (Fe), chromium (Cr), and nickel), and
      one metalloid (arsenic (As)) were measured in sediment, common reed (Phragmites
      australis), algae (Spirogyra sp.), and blood worm (Chironomus sp.) tissues of
      samples collected from the Shoor river. Samples were dried, acid digested, and
      the concentrations of metals were measured using inductively coupled plasma
      optical emission spectrometer. A higher concentration of heavy metals was
      accumulated in Spirogyra and Chironomids than sediment and common reed. The
      highest rate of accumulation was found for Mg, V, Fe, As, Cu, and Cr. Spirogyra
      and Chironomids are capable of accumulating and thereby removing metals from
      polluted water bodies and are suitable for biomonitoring purposes. 

PMID- 24105066
TI  - Effect of feeding graded doses of citrinin on apoptosis and oxidative stress in
      male Wistar rats through the F1 generation.
AB  - The objective of the present study was to study the effect of graded doses of
      citrinin (CIT) on apoptosis and oxidative stress in male Wistar rats till F1
      generation. The animals were divided into four groups comprising 25 males and 25
      females each, that is, group I: 1 ppm CIT; group II: 3 ppm CIT; group III: 5 ppm
      CIT; and group IV was kept as a control. The male and female animals of all the
      groups were kept separately and were fed basal rations containing the above
      mentioned concentrations of CIT for 10 weeks. After 10 weeks, male and female
      animals of respective groups were kept for mating (one male/two females). After
      getting 10 pregnant females, the males were killed. These 10 pregnant females
      were allowed to give birth to young ones (F1 generation) naturally which were fed
      CIT in the above-mentioned doses till the age of 6 weeks and then were killed.
      Apoptosis was analysed in kidneys, liver and testes by DNA ladder pattern,
      terminal deoxynucleotidyl transferase deoxyuridine triphosphate nick end
      labelling assay and Bcl-2/Bax ratio. Besides, tissue oxidative stress was also
      analysed. It was concluded in the present study that CIT induces its toxic
      effects till F1 generation, and apoptosis and oxidative stress both play a very
      important role in toxicity. The effect of CIT was observed in a dose-dependent
      manner. However, in kidneys, both the mechanisms (apoptosis and oxidative stress)
      play their role in inflicting renal damage, while in liver only reactive oxygen
      species play a major role. Finally, the CIT toxicity did not lead to apoptosis
      and oxidative stress in male gonads till F1 generation.

PMID- 24105067
TI  - Oral nanoparticulate curcumin combating arsenic-induced oxidative damage in
      kidney and brain of rats.
AB  - Arsenic exposure through drinking water causes oxidative stress and tissue damage
      in the kidney and brain. Curcumin (CUR) is a good antioxidant with limited
      clinical application because of its hydrophobic nature and limited
      bioavailability, which can be overcome by the encapsulation of CUR with
      nanoparticles (NPs). The present study investigates the therapeutic efficacy of
      free CUR and NP-encapsulated CUR (CUR-NP) against sodium arsenite-induced renal
      and neuronal oxidative damage in rat. The CUR-NP prepared by emulsion technique
      and particle size ranged between 120 and 140 nm, with the mean particle size
      being 130.8 nm. Rats were divided into five groups (groups 1-5) with six animals
      in each group. Group 1 served as control. Group 2 rats were exposed to sodium
      arsenite (25 ppm) daily through drinking water for 42 days. Groups 3, 4, and 5
      were treated with arsenic as in Group 2; however, these animals were also
      administered with empty NPs, CUR (100 mg/kg body weight), and CUR-NP (100 mg/kg),
      respectively, by oral gavage during the last 14 days of arsenic exposure. Arsenic
      exposure significantly increased serum urea nitrogen and creatinine levels.
      Arsenic increased lipid peroxidation (LPO), reduced glutathione content and the
      activities of superoxide dismutase, catalase, glutathione peroxidase, and
      glutathione reductase were depleted significantly in both kidney and brain.
      Treatment with free CUR and CUR-NP decreased the LPO and increased the enzymatic
      and nonenzymatic antioxidant system in kidney and brain. Histopathological
      examination showed that kidney and brain injury mediated by arsenic was
      ameliorated by treatment. However, the amelioration percentage indicates that CUR
      NP had marked therapeutic effect on arsenic-induced oxidative damage in kidney
      and brain tissues. 

PMID- 24105068
TI  - Chronic exposure of Rutilus rutilus caspicus fingerlings to ambient copper:
      Effects on food intake, growth performance, biochemistry and stress resistance.
AB  - An 8-week trial was conducted to investigate the effect of ambient copper (Cu) on
      growth performance, physiological characteristics and stress resistance of
      Caspian roach, Rutilus rutilus caspicus. Fish were exposed to 0 (control), 0.02,
      0.04 and 0.06 ppm Cu, and their food intake and growth performance were
      fortnightly recorded. Also, serum cortisol, glucose, alanine aminotransferase
      (ALT) and sodium (Na) levels were determined after 2 and 8 weeks exposure to
      ambient Cu. At the end of trial, serum total protein, albumin, globulin and
      albumin-globulin ratio (A:G) levels, whole body proximate composition and stress
      tolerance of the fish were measured. Results showed that Cu exposure resulted in
      a significant suppression in food intake after 2 weeks, which was eliminated
      after 4 weeks in 0.02 ppm groups and after 6 weeks in 0.04 and 0.06 ppm groups.
      Cu exposure brought about an inferior growth that recovered in line with the
      experiment progression, following a dose-dependent manner. Cu-exposed fish showed
      a dose-dependent increase in serum cortisol, glucose and ALT as well as decrease
      in serum Na, after 2 weeks. These parameters showed a full recovery in 0.02 ppm
      group and a partial recovery in 0.04 and 0.06 ppm groups, at the 8th week.
      Significant suppression in serum total protein, albumin, globulin and A:G levels
      and whole body dry matter, lipid and protein levels as well as stress resistance
      was observed in 0.04 and 0.06 ppm groups. It is concluded that Cu exposure could
      adversely affect growth performance, physiological characteristics and stress
      resistance of Caspian roach, which might affect its ecological features.

PMID- 24105069
TI  - Monocrotophos induced oxidative stress and alterations in brain dopamine and
      serotonin receptors in young rats.
AB  - Human exposure to monocrotophos, an organophosphate pesticide, could occur due to
      its high use in agriculture to protect crops. Recently, we found that
      postlactational exposure to monocrotophos impaired cholinergic mechanisms in
      young rats and such changes persisted even after withdrawal of monocrotophos
      exposure. In continuation to this, the effect of monocrotophos on noncholinergic
      targets and role of oxidative stress in its neurotoxicity has been studied.
      Exposure of rats from postnatal day (PD)22 to PD49 to monocrotophos (0.50 or 1.0
      mg kg(-1) body weight, perorally) significantly impaired motor activity and motor
      coordination on PD50 as compared to controls. A significant decrease in the
      binding of (3)H-spiperone to striatal membrane (26%, p < 0.01; 30%, p < 0.05) in
      rats exposed to monocrotophos at both the doses and increase in the binding of
      (3)H-ketanserin to frontocortical membrane (14%, p > 0.05; 37%, p < 0.05) in
      those exposed at a higher dose, respectively, was observed on PD50 compared with
      the controls. Alterations in the binding persisted even after withdrawal of
      monocrotophos exposure on PD65. Increased oxidative stress in brain regions
      following exposure of rats to monocrotophos was also observed on PD50 that
      persisted 15 days after withdrawal of exposure on PD65. The results suggest that
      monocrotophos exerts its neurobehavioral toxicity by affecting noncholinergic
      functions involving dopaminergic and serotonergic systems associated with
      enhanced oxidative stress. The results also exhibit vulnerability of developing
      brain to monocrotophos as most of the changes persisted even after withdrawal of
      its exposure.

PMID- 24105070
TI  - Allelopathic effect of methanolic extracts of genetically modified and non
      genetically modified canola on soybean.
AB  - This study on the effect of genetically modified (GM) and non-GM canola on
      soybean was carried out for physiological and biochemical biosafety assessment of
      GM canola. Methanolic extracts of GM and non-GM canola were assessed on seed
      germination and growth of soybean (Glycine max L.) under sterilized conditions.
      The extracts applied were of 3, 5, and 10% concentrations. The results showed
      that methanolic extracts of both GM and non-GM canola improved the germination
      percentage. However, germination rate index was significantly decreased with
      concomitant increase in mean germination time of soybean. A significant rate of
      decrease was observed in root fresh weight while increase in shoot length took
      place; when treatment of GM canola extracts were applied, however, no effect was
      observed in shoot fresh weight. A significant increase in protein contents, as
      well as phenolic, carotenoids, proline, and chlorophyll a content, was observed
      when different GM canola treatments (3, 5, and 10%) were applied to soybean;
      however, a significant rate of reduction in chlorophyll b content was observed by
      the application of GM canola treatment. Similar results were observed for
      superoxide dismutase, peroxidase, and catalase activities. A significant increase
      in the sugar content levels was observed when GM canola treatments (3, 5, and
      10%) were applied to soybean. 

PMID- 24105071
TI  - Association of serum pigment epithelium-derived factor with high-sensitivity C
      reactive protein in women with polycystic ovary syndrome.
AB  - BACKGROUND: The basic studies showed that Pigment epithelium-derived factor
      (PEDF) plays an important role in inflammation. AIM: This study aims to
      investigate the association of serum PEDF with high-sensitivity C-reactive
      protein (hs-CRP) in women with polycystic ovary syndrome (PCOS). METHODS: Ninety
      six PCOS women and 63 healthy, age-matched controls were enrolled in this study.
      Serum levels of PEDF, hs-CRP, Complement C3 (C3), glucose, insulin, lipids, and
      total testosterone were measured. Ninety-six PCOS women and 20 controls underwent
      hyperinsulinemiceuglycemic clamp to assess their insulin sensitivity, which was
      expressed as M value. RESULTS: Serum PEDF levels and hs- CRP levels were much
      higher in PCOS women than in controls. In PCOS women, PEDF positively correlated
      with body mass index (BMI), hs-CRP, C3, LDL cholesterol (LDL-c), and systolic
      blood pressure (SBP), and negatively correlated with M value and HDL cholesterol
      (HDL-c). After controlling for BMI, PEDF was still positively correlated with hs
      CRP. Multiple linear regression analysis revealed that in PCOS women, hs-CRP,
      SBP, LDL-c and M value were independent determinants of serum PEDF. CONCLUSION:
      The serum PEDF levels are closely associated with hs-CRP in women with PCOS. PEDF
      may play a role in the development of chronic inflammation in PCOS.

PMID- 24105072
TI  - Clinical efficacy and metabolic impact of two different dosages of ethinyl
      estradiol in association with drospirenone in normal-weight women with polycystic
      ovary syndrome: a randomized study.
AB  - BACKGROUND: The estrogenic component of estro- progestin (EP) is responsible for
      a negative impact on the metabolic and lipid assessment in women with polycystic
      ovary syndrome (PCOS). AIM: To evaluate the risk/benefit ratio of two EP
      combinations, containing the same progestin (3 mg drospirenone) and a different
      dose of ethinyl-estradiol (EE) (20 vs 30 MUg) and to compare their effects on the
      clinical and endocrine-metabolic parameters in normal-weight PCOS women.
      MATERIAL/SUBJECTS AND METHODS: In this randomized pilot study, we enrolled 30
      young normal-weight PCOS women. Fifteen subjects were allocated to group A (20
      MUg EE) and 15 PCOS subjects to group B (30 MUg EE). Hirsutism score, hormonal
      assays, oral glucose tolerance test, euglycemic hyperinsulinemic clamp and lipid
      profile were performed at baseline, and after 6 and 12 months of therapy. Main
      outcome measures were signs of hyperandrogenism, glucose and insulin metabolism,
      lipid profile. RESULTS: Both treatment regimens induced a significant improvement
      in hirsutism score, testosterone, DHEAS, and SHBG levels. Androstenedione
      significantly dropped only in patients of Group A, while 17(OH)P only in those
      from Group B. Both the formulations did not significantly modify gluco
      insulinemic metabolism. Total cholesterol, LDL cholesterol, and HDL cholesterol
      levels significantly increased in both groups. Triglycerides levels, which
      increased as well, resulted more markedly influenced by the formulation with 30
      MUg EE. CONCLUSIONS: In association with drospirenone, 20 MUg EE results as
      effective as 30 MUg in improving clinical and hormonal features of normal-weight
      PCOS women, while exhibiting a milder influence on lipidic parameters.

PMID- 24105073
TI  - Glucose intolerance states in women with the polycystic ovary syndrome.
AB  - The polycystic ovary syndrome (PCOS), the most common hyperandrogenic disorder
      affecting 4-7% of women, is often associated with metabolic alterations, chiefly
      insulin resistance and obesity. Based on available scientific evidence, PCOS
      should be regarded as an independent risk for the development of glucose
      intolerance states. This short review summarizes the available literature on the
      prevalence and incidence of impaired glucose tolerance and Type 2 diabetes in
      this disorder. In addition, some insights on potential factors responsible for
      individual susceptibility are discussed. Targeted intervention studies focused on
      prevention and treatment of glucose intolerance states in PCOS are warranted. 

PMID- 24105075
TI  - Randomized phase 2 study of pegylated SN-38 (EZN-2208) or irinotecan plus
      cetuximab in patients with advanced colorectal cancer.
AB  - BACKGROUND: Irinotecan is cytotoxic in patients with advanced colorectal cancer
      (CRC). SN-38 (10-hydroxy-7-ethyl-camptothecin) is the active metabolite of
      irinotecan. Attachment of polyethylene glycol (PEG) polymer chains (pegylation)
      to SN-38 (EZN-2208) increases the solubility, exposure, and half-life of SN-38.
      Preclinical studies demonstrated superior in vitro efficacy of EZN-2208 when it
      was tested in irinotecan-refractory human CRC cell lines. METHODS: Patients with
      metastatic or locally recurrent CRC who had previously received 5-flurouracil (5
      FU), oxaliplatin, and irinotecan were assigned to receive EZN-2208 monotherapy (9
      mg/m(2) on days 1, 8, and 15 every 28 days for patients with KRAS-mutant tumors
      only [arm A]), and patients with KRAS wild-type tumors were randomized (2:1) to
      receive either EZN-2208 plus cetuximab (400 mg/m(2) loading dose on day 1
      followed by 250 mg/m(2) weekly starting on day 8 [arm B]) or irinotecan 125
      mg/m(2) on days 1 and 8 every 21 days plus cetuximab at the same doses indicated
      above (arm C). RESULTS: The overall response rate and progression-free survival
      were 0% and 1.8 months, respectively, in arm A; 10.7% and 4.9 months (95%
      confidence interval [CI], 3.2-5.8 months), respectively, in arm B; and 14.3% and
      3.7 months (95% CI, 2.1-5.8 months), respectively, in arm C. EZN-2208 was well
      tolerated in combination with cetuximab. No statistically significant difference
      in survival was observed between arm B (9.8 months; 95% CI, 7.2-11.2 months) and
      arm C (9.1 months; 95% CI, 6.0-13.0 months). CONCLUSIONS: EZN-2208, either as
      monotherapy or in combination with cetuximab, was well tolerated in patients with
      refractory CRC. Overall survival and progression-free survival were similar in
      the cetuximab plus irinotecan arm and the EZN-2208 arm.

PMID- 24105076
TI  - Detergent quantification in membrane protein samples and its application to
      crystallization experiments.
AB  - The structural characterization of membrane proteins remains a challenging field,
      largely because the use of stabilizing detergents is required. Researchers must
      first select a suitable detergent for the solubility and stability of their
      protein during in vitro studies. In addition, an appropriate concentration of
      detergent in membrane protein samples can be essential for protein solubility,
      stability, and experimental success. For example, in membrane protein
      crystallography, detergent concentration in the crystallization drop can be a
      critical parameter influencing crystal growth. Over the past decade, multiple
      techniques have been developed for the measurement of detergent concentration
      using a wide variety of strategies. These methods include colorimetric reactions,
      which target specific detergent classes, and analytical techniques applicable to
      a wide variety of detergents. This review will summarize and discuss the
      available options. It will be a useful resource to those selecting a strategy
      that best fits their experimental requirements and available instruments. 

PMID- 24105077
TI  - Indoleamine 2,3-dioxygenase 2 (IDO2) and the kynurenine pathway: characteristics
      and potential roles in health and disease.
AB  - The kynurenine pathway is the major route for the oxidative degradation of the
      amino acid tryptophan. Activity of the pathway is involved in several disease
      conditions, both in the periphery and the central nervous system, including
      cancer, inflammatory disorders, neurological conditions, psychiatric disorders
      and neurodegenerative diseases. Three enzymes are now known to catalyze the first
      and rate-limiting step in the catabolism of tryptophan along this pathway:
      tryptophan 2,3-dioxygenase (TDO) and indoleamine 2,3-dioxygenase (IDO,
      subsequently named IDO1), both of which have been extensively studied, and a
      third enzyme, indoleamine 2,3-dioxygenase 2 (IDO2), a relative newcomer to the
      kynurenine pathway field. The adjuvant chemotherapeutic agent, 1-methyl-D
      tryptophan, was intially suggested to target IDO2, implying involvement of IDO2
      in tumorigenesis. Subsequently this compound has been suggested to have
      alternative actions and the physiological and pathophysiological roles of IDO2
      are unclear. Targeted genetic interventions and selective inhibitors provide
      approaches for investigating the biology of IDO2. This review focuses on the
      current knowledge of IDO2 biology and discusses tools that will assist in further
      characterizing the enzymes of the kynurenine pathway. 

PMID- 24105078
TI  - Prevalence of medication use for somatic disease in institutionalized psychiatric
      patients.
AB  - INTRODUCTION: Psychiatric patients may use medications for their psychiatric
      condition as well as for treating concurrent somatic diseases or somatic side
      effects of psychiatric medicines. The objective of this study was to estimate the
      prevalence of use of medication for somatic disease in institutionalized
      psychiatric patients and changes therein during 2006-2010. METHOD: A cross
      sectional study in institutionalized psychiatric patients was performed.
      Medication use for somatic disease on 10 time points between 2006 and 2010 was
      investigated and stratified by gender, age, psychiatric medication class and the
      number of different psychiatric medication classes used. RESULTS: The prevalence
      of use of medication for somatic disease increased from 67.5% in 2006 to 76.9% in
      2010. The median number of medications used for somatic disease per patient was 3
      between 2006 and 2010. Approximately one-third (34.1%) of the patients received
      >= 3 medications intended for treating somatic disease in 2006 which increased to
      46.3% in 2010. In 2010, the prevalence of medication use for somatic disease was
      highest for analgesics and antirheumatics (34.0%), acid and bowel related
      medication (25.6%) and anticholinergic medication (24.2%). Medication use for
      somatic disease was highest in patients >= 60 years (95.3%), patients treated
      with more than one psychiatric medication class (87.5%) and patients treated with
      mood stabilizers (90.6%). DISCUSSION: Somatic medication use is high in
      institutionalized psychiatric patients. More attention is needed for co-use of
      psychiatric and somatic medications to prevent side effects, drug-disease or drug
      drug interactions. More research is needed to investigate if somatic care is
      optimal in institutionalized psychiatric patients.

PMID- 24105079
TI  - Association between antidepressant prescribing and suicide rates in OECD
      countries: an ecological study.
AB  - INTRODUCTION: We have conducted an ecological study to assess the association
      between antidepressant prescribing and suicide rates using the Organisation for
      Economic Co-operation and Development (OECD) health data, making this the largest
      ecological study in recent times. METHOD: Data were derived for the years 1995
      2008 from the OECD health data set. The residuals for all variables were adjusted
      for country and year within each country. These were then analysed to identify
      predictors of suicide rate. Pearson's rank correlation coefficient and linear
      regression model were employed to assess associations and identify significant
      predictors of suicide rate. RESULTS: Suicide rate has significant positive
      correlations with antidepressant rates (p=0.031) and unemployment (p=0.028). It
      also has a significant negative correlation with inpatient psychiatric beds
      (p=0.039). The actual coefficients are less than +/-0.16, indicating weak
      relationships. After adjusting for other variables, the only variable that is a
      statistically significant predictor of suicide rate is antidepressant prescribing
      (p=0.005, r2=0.09). DISCUSSION: Our analysis using this large data set suggests a
      statistically significant, albeit weak positive, association between
      antidepressant prescribing and suicide rates.

PMID- 24105074
TI  - Moonlighting proteins and protein-protein interactions as neurotherapeutic
      targets in the G protein-coupled receptor field.
AB  - There is serious interest in understanding the dynamics of the receptor-receptor
      and receptor-protein interactions in space and time and their integration in GPCR
      heteroreceptor complexes of the CNS. Moonlighting proteins are special
      multifunctional proteins because they perform multiple autonomous, often
      unrelated, functions without partitioning into different protein domains.
      Moonlighting through receptor oligomerization can be operationally defined as an
      allosteric receptor-receptor interaction, which leads to novel functions of at
      least one receptor protomer. GPCR-mediated signaling is a more complicated
      process than previously described as every GPCR and GPCR heteroreceptor complex
      requires a set of G protein interacting proteins, which interacts with the
      receptor in an orchestrated spatio-temporal fashion. GPCR heteroreceptor
      complexes with allosteric receptor-receptor interactions operating through the
      receptor interface have become major integrative centers at the molecular level
      and their receptor protomers act as moonlighting proteins. The GPCR
      heteroreceptor complexes in the CNS have become exciting new targets for
      neurotherapeutics in Parkinson's disease, schizophrenia, drug addiction, and
      anxiety and depression opening a new field in neuropsychopharmacology. 

PMID- 24105080
TI  - Inhibition of olanzapine-induced weight gain by the retinoid analog AM-80.
AB  - INTRODUCTION: Weight gain and metabolic abnormalities are common side effects of
      antipsychotic treatment. Retinoids have been suggested as promising substances to
      suppress obesity. This study has investigated the effects of a retinoid agonist
      AM-80 on olanzapine-induced weight gain and metabolic changes in rats. METHODS:
      Female Sprague-Dawley rats (7 weeks) were treated with AM-80 (1 mg/kg/day,
      subcutaneously) and/or olanzapine (4 mg/kg/day, intraperitoneally) for 21 days.
      Body weight and food/water intake were measured daily. The open field (OFT) and
      prepulse inhibition (PPI) tests were done on days 18 and 21, respectively.
      Animals were sacrificed on day 22 to measure weight of adipose tissues and serum
      levels of adiponectin and leptin levels. RESULTS: Olanzapine significantly
      increased body weight, food/water intake and the mass of inguinal adipose tissue
      (IAT) compared to vehicle-treated rats. AM-80 demonstrated significant inhibition
      of weight gain. No significant effect of olanzapine or AM-80 was found on
      behaviors or serum adiponectin/leptin levels. CONCLUSION: These findings suggests
      that AM-80 is a potential therapeutic agent to attenuate weight gain and
      metabolic side effects associated with olanzapine.

PMID- 24105081
TI  - Female neuregulin 1 heterozygous mice require repeated exposure to Delta9
      tetrahydrocannabinol to alter sensorimotor gating function.
AB  - INTRODUCTION: The schizophrenia susceptibility gene neuregulin 1 (NRG1) confers
      vulnerability to the neurobehavioural eff ects of cannabinoids differently across
      sexes. Male but not female Nrg1 heterozygous (HET) mice display facilitation of
      prepulse inhibition (PPI) to acute Delta9-tetrahydrocannabinol (THC) exposure
      compared to WT controls. We aim to observe whether repeated administration of THC
      may overcome the acute insensitivity of female Nrg1 HET mice to THC exposure.
      METHODS: Female Nrg1 HET mice and WT controls were administered THC daily for 21
      days, with PPI and anxiety-related behaviour in the light-dark test (LD) examined
      on the fi rst and last day of treatment and 21 days after cessation of dosing.
      RESULTS: Following repeated, but not acute THC exposure, female Nrg1 HET mice
      displayed THC-induced facilitation of PPI which was not observed in WT mice
      treated with THC. There were no residual eff ects of THC on PPI in either
      genotype when assessed 21 days following the final THC dose. An anxiogenic
      response to THC was evident following repeated, but not acute, administration in
      the LD test in both genotypes. DISCUSSION: These findings show that the acute
      insensitivity of female Nrg1 HET mice to THC-induced PPI facilitation may be
      overcome following repeated THC exposure.

PMID- 24105083
TI  - Stable isotope ratio analysis of breastfeeding and weaning practices of children
      from medieval Fishergate House York, UK.
AB  - Rib collagen of 51 juveniles and 11 adult females from the late medieval
      Fishergate House cemetery site (York, UK) were analyzed using nitrogen and carbon
      stable isotope ratio analysis to determine the weaning age for this population
      and to reconstruct diet. The juveniles' ages ranged from fetal to 5-6 years,
      while the females were of reproductive age. Previous researchers suggested that
      the children from Fishergate House might have been weaned later than the medieval
      British norm of 2 years, based on a mortality peak at 4-6 years of age. The
      results show weaning was complete by 2 years of age, agreeing with previous
      British weaning studies. The adult female delta(15) N values have a mean of
      11.40/00 +/- 1.10/00 and the delta(13) C values have a mean of -19.40/00 +/-
      0.40/00. These findings are consistent with previous isotopic studies of female
      diet in York during this period, though slightly lower. The weaned juvenile
      nitrogen values were found to be higher than the adult females (12.40/00 +/-
      1.00/00 for delta(15) N and -19.70/00 +/- 0.50/00 for delta(13) C), which might
      indicate a dependence on higher trophic level proteins such as marine fish or
      pork. Marine fish is considered a high status food and children are considered
      low-status individuals at this time, making this a particularly interesting
      finding. Weaning does not appear to coincide with peak mortality, suggesting
      environment factors may be playing a larger role in child mortality at Fishergate
      House.

PMID- 24105082
TI  - Intestinal microbiome and digoxin inactivation: meal plan for digoxin users?
AB  - There is an increasing interest in the role of intestinal microbiome in human
      diseases and therapeutic agents' bioavailability, activity and toxicity.
      Epidemiological data show that the bioavailability of digoxin, a widely used
      agent for heart disease, varies among individuals. The inactivation of digoxin
      was found when it was incubated with gut bacterium Eggerthella lenta in vitro
      decades ago. However, the underlying mechanisms of digoxin inactivation are still
      unclear. A recent study using animal models uncovered this mystery, which
      suggested that arginine supplements might be a potential intervention in
      increasing digoxin activity by inhibiting the expression of cardiac glycoside
      reductase gene operons that inactivated digoxin. This perspective summarizes the
      connections among the intestinal microbiome, the digoxin inactivation, the
      metabolism of arginine. We also discuss several issues yet to be addressed in the
      future, making better strategies in the application of dietary arginine
      supplements for digoxin users. 

PMID- 24105084
TI  - The embrace device significantly decreases scarring following scar revision
      surgery in a randomized controlled trial.
AB  - BACKGROUND: Mechanically offloading or shielding an incision significantly
      reduces scarring in both animal and first-in-human studies. Whether or not this
      strategy would be effective following scar revision surgery was previously
      unknown. In this article, the authors report that the embrace device, which uses
      principles of mechanomodulation, significantly improves aesthetic outcomes
      following scar revision surgery. METHODS: A prospective, open-label, randomized,
      single-center study was conducted to evaluate the appearance of scars following
      revision and embrace treatment. Revision surgery was performed on 12 patients,
      each acting as his or her own control, and outcomes were assessed at 6 months. A
      visual analogue scale was used to evaluate each scar, rated by four independent
      surgeons who were not involved in the study. RESULTS: Evaluation of 6-month scar
      images by four independent surgeons using the visual analogue scale demonstrated
      a highly significant improvement in scar appearance following embrace treatment
      (p < 0.005). CONCLUSION: The embrace device represents a powerful new technology
      for significantly improving scar appearance following revision surgery. CLINICAL
      QUESTION/LEVEL OF EVIDENCE: Therapeutic, II.

PMID- 24105085
TI  - Applications of acellular dermal matrix in revision breast reconstruction
      surgery.
AB  - BACKGROUND: Acellular dermal matrix has been used for over a decade in primary
      breast reconstruction. Few articles have specifically examined its use in
      revision breast reconstruction for fold malposition, capsular contracture,
      rippling, and symmastia. METHODS: One hundred thirty-five revision breast
      reconstructive procedures using acellular dermal matrix (AlloDerm) in 118
      patients (154 breasts) over a 5-year period were reviewed. Most procedures were
      revisions or part of the second stage of previous mastectomy reconstructions;
      three were revisions after reconstruction of congenital chest wall deformities.
      RESULTS: Fifty-seven revisions (37 percent) were for inferior fold malposition,
      followed by 40 (25.9 percent) for inferior pole support, 42 (27.2 percent) for
      capsular contracture, 10 (6.4 percent) for rippling, and five (3.2 percent) for
      symmastia. The overall complication rate was 5 percent. Revisions with acellular
      dermal matrix were successful in 147 of 154 breasts (95.5 percent). The most
      common complication was capsular contracture, occurring in five breasts (3.2
      percent). There was one infection (0.6 percent), failure to lower the
      inframammary fold in one breast (0.6 percent), and one persistence of rippling
      (0.6 percent). The mean follow-up was 207 days. CONCLUSIONS: Acellular dermal
      matrix has proven to be a reliable tool for managing some of the most common and
      challenging problems in implant-based breast reconstruction. Although there are
      few published data on the success of more conventional solutions to fold
      malposition, lower pole support, and capsular contracture, the addition of
      acellular dermal matrix to buttress these repairs has been shown to provide a
      high likelihood of success with a low risk of complications.

PMID- 24105086
TI  - Measuring outcomes that matter to face-lift patients: development and validation
      of FACE-Q appearance appraisal scales and adverse effects checklist for the lower
      face and neck.
AB  - BACKGROUND: The FACE-Q is a new patient-reported outcome instrument to evaluate a
      range of outcomes for patients undergoing any type of facial cosmetic operation,
      minimally invasive cosmetic procedure, or facial injectable. This article
      describes the development and validation of FACE-Q scales relevant to face-lift
      patients. METHODS: The FACE-Q was developed by following international guidelines
      for patient-reported outcome instrument development. For outcomes following a
      face lift, the authors developed five appearance appraisal scales (i.e.,
      Satisfaction with Cheeks, Satisfaction with Lower Face and Jawline, Appraisal of
      Nasolabial Folds, Appraisal of Area Under the Chin, and Appraisal of the Neck)
      and an adverse effects checklist. A field test of these scales was performed in a
      sample of 225 face-lift patients, and were evaluated using both modern and
      traditional psychometric methods. RESULTS: The five FACE-Q appearance appraisal
      scales were found to be clinically meaningful, reliable, valid, and responsive to
      clinical change. These findings were supported by Rasch measurement theory
      analysis (e.g., overall chi-square values of p >= 0.18; Person Separation Index
      >= 0.88). Responsiveness analyses showed that patient scores for facial
      appearance improved significantly after treatment (p < 0.001); changes in scores
      were associated with moderate effect sizes (range effect size, 0.40 to 0.79;
      range standardized response mean, 0.37 to 0.69). Traditional psychometric
      statistics provided further support (e.g., Cronbach's alpha values >= 0.94)
      CONCLUSIONS:: The FACE-Q appearance appraisal scales are scientifically sound and
      clinically meaningful and can be used with the adverse effects checklist to
      measure patient-reported outcomes following a face lift.

PMID- 24105087
TI  - Massive panniculectomy in the super obese and super-super obese: retrospective
      comparison of primary closure versus partial open wound management.
AB  - BACKGROUND: The incidence of obesity is on the rise in the United States and
      worldwide. Complications following panniculectomy are higher for super obese
      patients, often requiring readmission and additional interventions. In this
      study, the authors compare the outcomes of patients who underwent primary closure
      of their resection wounds to the outcomes of patients who underwent initial open
      wound management with a negative-pressure dressing. METHODS: The records of all
      patients who underwent panniculectomy between 2007 and 2012 were reviewed. Of 14
      patients with a body mass index greater than 50, nine underwent primary closure
      and five were treated with open wound management. A retrospective chart review
      was performed. RESULTS: There were no statistically significant differences in
      age or preoperative comorbidities, but body mass index was higher for the open
      wound management group (66.4 versus 58.9, p = 0.039). There were no statistically
      significant differences in mean operative time, resection weight, estimated blood
      loss, or hospital length of stay. The primary closure group had a 44 percent
      readmission rate and a 33 percent reoperation rate for wound complications. The
      open wound management group had no wound-related readmissions or secondary
      procedures for debridement. CONCLUSIONS: Open wound management in the massive
      panniculectomy patient reduces hospital readmission and secondary operations.
      This case series provides reasons to support the consideration of open wound
      management following massive panniculectomy in the super morbidly obese patient
      population.

PMID- 24105088
TI  - Comparative outcomes of two nasoalveolar molding techniques for bilateral cleft
      nose deformity.
AB  - BACKGROUND: Bilateral cleft nose deformity is increasingly being treated before
      primary repair with nasoalveolar molding. With the Grayson technique, nasal
      molding is started when the alveolar gap is reduced to 5 mm, whereas with the
      Figueroa technique, nasal molding and alveolar molding are performed at the same
      time. Both techniques significantly lengthen the columella, but their comparative
      efficacy, efficiency, and incidence of complications have not been investigated.
      METHODS: In this blinded, retrospective study of 58 patients with complete
      bilateral cleft lip-cleft palate, 27 underwent Grayson nasoalveolar molding and
      31 underwent Figueroa nasoalveolar molding. Outcomes were compared by analyzing
      pretreatment and posttreatment facial photographs and clinical charts for
      efficacy (i.e., columella length ratio, alar width ratio, alar base width ratio,
      nostril shape, nasal tip angle, nasolabial angle, and nasal base angle),
      efficiency (i.e., molding frequency), and incidence of complications (e.g.,
      facial irritation and oral mucosal ulceration). RESULTS: Grayson and Figueroa
      nasoalveolar molding did not differ in treatment efficacy for columellar length
      ratio, alar width ratio, alar base width ratio, nostril shape, nasal tip angle,
      nasolabial angle, or nasal base angle (all p > 0.05). Grayson nasoalveolar
      molding was less efficient (i.e., required more adjustments) (10.8 +/- 4.1 versus
      7.6 +/- 1.5; p = 0.001) and had a higher incidence of oral mucosal ulceration (26
      percent versus 3 percent; p < 0.05). CONCLUSIONS: Both Grayson and Figueroa
      nasoalveolar molding similarly improve nasal deformities and reduce alveolar
      gaps; however, the Figueroa technique is associated with fewer oral mucosal
      complications and more efficiency.

PMID- 24105089
TI  - Soft-tissue coverage of the hand: a case-based approach.
AB  - Adequate soft-tissue coverage of the hand is paramount to achieve optimal
      aesthetic and functional results in patients with complex hand defects. In this
      article, the authors present four illustrative clinical cases and discuss
      potential reconstructive modalities. For each scenario, two surgical options are
      discussed: one established and one nontraditional method of reconstruction. The
      authors' preferred method and technical pearls for execution are presented.

PMID- 24105090
TI  - Predictors of readmission after outpatient plastic surgery.
AB  - BACKGROUND: Hospital readmissions have become a topic of focus for quality care
      measures and cost-reduction efforts. However, no comparative multi-institutional
      data on plastic surgery outpatient readmission rates currently exist. The authors
      endeavored to investigate hospital readmission rates and predictors of
      readmission following outpatient plastic surgery. METHODS: The 2011 National
      Surgical Quality Improvement Program database was reviewed for all outpatient
      procedures. Unplanned readmission rates were calculated for all 10 tracked
      surgical specialties (i.e., general, thoracic, vascular, cardiac, orthopedics,
      otolaryngology, plastics, gynecology, urology, and neurosurgery). Multivariate
      logistic regression models were used to determine predictors of readmission for
      plastic surgery. RESULTS: A total of 7005 outpatient plastic surgery procedures
      were isolated. Outpatient plastic surgery had a low associated readmission rate
      (1.94 percent) compared with other specialties. Seventy-five patients were
      readmitted with a complication. Multivariate regression analysis revealed obesity
      (body mass index >= 30), wound infection within 30 days of the index surgery, and
      American Society of Anesthesiologists class 3 or 4 physical status as significant
      predictors for unplanned readmission. CONCLUSIONS: Unplanned readmission after
      outpatient plastic surgery is infrequent and compares favorably to rates of
      readmission among other specialties. Obesity, wound infection within 30 days of
      the index operation, and American Society of Anesthesiologists class 3 or 4
      physical status are independent predictors of readmission. As procedures continue
      to transition into outpatient settings and the drive to improve patient care
      persists, these findings will serve to optimize outpatient surgery use.

PMID- 24105091
TI  - Effect of endoscopic brow lift on contractures and synkinesis of the facial
      muscles in patients with a regenerated postparalytic facial nerve syndrome.
AB  - BACKGROUND: Delayed recovery after facial palsy results in aberrant nerve
      regeneration with symptomatic movement disorders, summarized as the postparalytic
      facial nerve syndrome. The authors present an alternative surgical approach for
      improvement of periocular movement disorders in patients with postparalytic
      facial nerve syndrome. The authors proposed that endoscopic brow lift leads to an
      improvement of periocular movement disorders by reducing pathologically raised
      levels of afferent input. METHODS: Eleven patients (seven women and four men)
      with a mean age of 54 years (range, 33 to 85 years) and with postparalytic facial
      nerve syndrome underwent endoscopic brow lift under general anesthesia. Patients'
      preoperative condition was compared with their postoperative condition using a
      retrospective questionnaire. Subjects were also asked to compare the therapeutic
      effectiveness of endoscopic brow lift and botulinum toxin type A. RESULTS: Mean
      follow-up was 52 months (range, 22 to 83 months). No intraoperative or
      postoperative complications occurred. During follow-up, patients and physicians
      observed an improvement of periorbital contractures and oculofacial synkinesis.
      Scores on quality of life improved significantly after endoscopic brow lift. Best
      results were obtained when botulinum toxin type A was adjoined after the
      endoscopic brow lift. Patients described a cumulative therapeutic effect.
      CONCLUSIONS: These findings suggest endoscopic brow lift as a promising
      additional treatment modality for the treatment of periocular postparalytic
      facial nerve syndrome-related symptoms, leading to an improved quality of life.
      Even though further prospective investigation is needed, a combination of
      endoscopic brow lift and postsurgical botulinum toxin type A administration could
      become a new therapeutic standard.

PMID- 24105092
TI  - The anterolateral thigh flap for groin and lower abdominal defects: a better
      alternative to the rectus abdominis flap.
AB  - BACKGROUND: Historically, the mainstay of soft-tissue reconstruction in the groin
      and lower abdomen has been the anatomically consistent, easily elevated rectus
      abdominis flap, with variations. Insetting the rectus abdominis flap here
      requires creating an abdominal wall defect through which to pass the pedicle,
      which raises the risk of donor-site morbidity. Although popular as a free flap,
      the anterolateral thigh flap as a pedicled flap in the groin and lower abdomen
      has not been directly compared with the rectus abdominis flap. METHODS:
      Retrospective record review was conducted on 39 patients who underwent groin or
      lower abdominal wall reconstruction (30 anterolateral thigh flap and 10 rectus
      abdominis flap procedures) to address oncologic defects, lymphadenectomy, and
      complications of vascular bypass. Patient demographics and comorbidities, flap
      characteristics, postoperative complications, and time to heal were compared.
      RESULTS: All patients in both the anterolateral thigh and rectus abdominis flap
      groups healed at the flap recipient sites. Despite similar patient
      characteristics, wound cause was different between the groups, with more infected
      wounds being treated in the anterolateral thigh flap group. Early postoperative
      complication rates were similar in both groups. Anterolateral thigh flap patients
      had shorter time to healing, with lower rates of delayed (>30 days) postoperative
      complications compared with rectus abdominis flap patients. Six rectus abdominis
      flap patients developed delayed abdominal incisional hernias. No donor- or
      recipient-site complications were encountered in anterolateral thigh flap
      patients after 90 days. CONCLUSION: The pedicled anterolateral thigh flap is the
      preferred choice for reconstruction of wounds in the groin and lower abdomen.

PMID- 24105097
TI  - Impact of delisting ARBs, apart from losartan, on ARB utilisation patterns in
      Denmark: implications for other countries.
AB  - INTRODUCTION: Renin-angiotensin inhibitor drugs have been a target for health
      authority initiatives across Europe with the potential for substantial savings
      once generic angiotensin-converting enzyme inhibitors (ACEIs) became available
      without compromising care. Recently, losartan was the first angiotensin receptor
      blocker (ARB) to lose its patent. In Denmark, the authorities removed all other
      ARBs from the reimbursement list, apart from losartan, as they were all seen as
      essentially similar for the management of hypertension or congestive heart
      failure at appropriate doses, but more expensive. Similarly, all other ARB fixed
      dose combinations (FDCs), apart from losartan, were removed from the
      reimbursement list. OBJECTIVE: The aims of the study were to (i) assess the
      impact of these reimbursement changes on the subsequent utilisation of losartan
      and other ARBs alone or as FDCs; (ii) assess changes in the prices of losartan
      and other ARBs post-generic losartan to calculate potential savings; and (iii)
      compare the impact of the policies in Denmark with other European countries to
      provide guidance. METHODOLOGY: This was a retrospective segmented regression
      analysis of an interrupted time-series design comparing utilisation patterns
      before and after the changes in ARB reimbursement status. Utilisation was
      measured in defined daily doses (DDDs). Changes in total expenditure and
      expenditure/DDD were also assessed over time. RESULTS: Losartan utilisation grew
      from 31 to 33 % of total single ARB utilisation before generic losartan, to 93 %
      by October 2011. There was a corresponding decrease in the utilisation of all
      other ARBs. Both changes were significant (p < 0.001). Total expenditure on
      single ARBs in 2011 was 77 % below 2009 levels despite a 16 % increase in
      utilisation. Estimated savings were 290.5 million Danish Kroner (DKK). A similar
      trend was seen for losartan FDCs, which was also significant (p < 0.001).
      DISCUSSION: Losartan utilisation grew appreciable following the changes. The
      change was much greater than seen in countries that had eased prescribing
      restrictions for losartan but not the other ARBs. Active therapeutic switching
      programmes plus education and financial incentives also significantly enhanced
      losartan utilisation following generics in two countries and regions; however,
      the increase in losartan utilisation was less than that seen in Denmark.

PMID- 24105098
TI  - Bond and mode selectivity in the OH + NH2D reaction: a quasi-classical trajectory
      calculation.
AB  - A state-to-state dynamics study was performed to analyze the effects of
      vibrational excitation on the dynamics of the OH + NH2D gas-phase reaction, which
      are connected to issues such as bond and mode selectivity. This reaction can
      evolve along two channels: H-abstraction, H2O(nu) + NHD(nu); and D-abstraction,
      HOD(nu) + NH2(nu). Based on an analytical potential energy surface previously
      developed by our group, quasi-classical trajectory calculations and subsequent
      normal mode analysis were performed. While vibrational excitation of the NH-sym
      mode of NH2D slightly favours H-abstraction over the D-abstraction, vibrational
      excitation of the ND mode shows that there is no clear preference for the H- or D
      abstraction. These results show that this reaction does not exhibit bond
      selectivity, suggesting a breakdown of the spectator model. For H-abstraction,
      vibrational excitation of the non-reactive ND mode is partially retained in the
      NHD product; and for D-abstraction, excitation of the non-reactive NH mode is
      also partially retained in the products, indicating that this reaction exhibits
      mode selectivity only partially. In sum, we rule out bond and mode selectivity
      for this reaction. All these results were interpreted on the basis of strong
      coupling between modes along the reaction path, a behaviour which seems to be
      more the general tendency than the exception in polyatomic reactions. 

PMID- 24105099
TI  - 1H, 13C and 15N resonance assignments for the full-length mammalian cytochrome b5
      in a membrane environment.
AB  - Microsomal cytochrome b5 plays a key role in the oxidation of a variety of
      exogenous and endogenous compounds, including drugs, fatty acids, cholesterol and
      steroid hormones. To better understand its functional properties in a membrane
      mimic environment, we carried out high-resolution solution NMR studies. Here we
      report resonance assignments for full-length rabbit cytochrome b5 embedded in
      dodecylphosphocholine micelles. 

PMID- 24105100
TI  - Association between alcohol consumption and plasma fetuin-A and its contribution
      to incident type 2 diabetes in women.
AB  - AIMS/HYPOTHESIS: The benefits of moderate alcohol consumption for type 2 diabetes
      have been postulated to involve a mechanism of improved insulin sensitivity.
      Fetuin-A, which is known to inhibit insulin signalling, has emerged as a
      biomarker for diabetes risk. Alcohol consumption may influence circulating fetuin
      A concentrations and subsequently diabetes risk by altering the insulin signal.
      We therefore hypothesised that moderate alcohol consumption would be associated
      with lower fetuin-A concentration and that fetuin-A would partly explain the
      association between alcohol consumption and incident type 2 diabetes. METHODS:
      Among diabetes-free female participants in the Nurses' Health Study (n = 1,331),
      multiple linear regression was conducted to assess the association between
      alcohol consumption and plasma fetuin-A. Least-squares means (lsmeans) of fetuin
      A were estimated in categories of alcohol consumption (0, 0.1-4.9, 5-14.9 and >=
      15 g/day). The proportion of alcohol consumption and diabetes association
      explained by baseline fetuin-A was assessed in 470 matched incident diabetes case
      control pairs with follow-up 2000-2006. RESULTS: Higher alcohol consumption was
      associated with lower plasma fetuin-A (p for trend = 0.009): lsmean +/- SE 476.5
      +/- 5.9 MUg/ml for abstainers, 468.9 +/- 5.2 MUg/ml for 0.1-4.9 g/day consumers,
      455.9 +/- 7.0 MUg/ml for 5.0-14.9 g/day consumers, and 450.0 +/- 9.4 MUg/ml for
      >= 15.0 g/day consumers. Fetuin-A and fasting insulin explained 18.4% and 54.8%,
      respectively, of the inverse association between alcohol consumption and diabetes
      after multiple adjustment (both p for contribution <0.04).
      CONCLUSIONS/INTERPRETATION: Moderate alcohol consumption is associated with lower
      plasma fetuin-A in diabetes-free women. Fetuin-A and insulin explain a
      significant proportion of the association between alcohol consumption and
      incident type 2 diabetes. Further studies are needed to examine potential
      biological mechanisms underlying this association.

PMID- 24105102
TI  - Synthesis, antimicrobial evaluation and QSAR studies of 2-hydroxy propanoic acid
      derivatives.
AB  - A series of 2-hydroxypropanoic acid derivatives (1-26) was synthesized and
      characterized by physicochemical and spectral means. The synthesized compounds
      were evaluated for their in vitro antimicrobial potential and the results
      indicated that compounds 5 and 12 were found to be the most potent antimicrobial
      agents having pMICam values 1.67 and 1.64 uM/ml respectively. QSAR studies
      indicated the importance of topological parameter, Kier's valance second order
      molecular connectivity index (2chiv) in describing the antimicrobial activities
      of synthesized 2-hydroxypropanoic acid derivatives. 

PMID- 24105101
TI  - Use of imaging and biomarker tests for posttreatment care of early-stage breast
      cancer survivors.
AB  - BACKGROUND: The American Society of Clinical Oncology (ASCO) recently released a
      "Top Five" list of opportunities to improve the quality of cancer care. Item 4 on
      the list advises against using advanced imaging and biomarkers for surveillance
      in patients with breast cancer who are treated with curative intent. This study
      examined concordance with ASCO follow-up care guidelines for breast cancer
      survivors treated at an academic medical center. METHODS: Claims data and medical
      records were reviewed and abstracted for early stage breast cancer survivors
      starting 1 year post diagnosis. A trained abstractor classified imaging tests as
      diagnostic or surveillance. Proportions and frequencies were generated for
      receipt of services. Multilevel logistic regression was used to estimate factors
      associated with receiving recommended and nonrecommended services and biomarker
      tests. RESULTS: Records were available for 258 patients. Mean age at diagnosis
      was 58 years (standard deviation of 13 years), mean time since diagnosis was 6
      years (standard deviation of 2 years), and 71% were stage 0/1. Only 47% of the
      sample received a mammogram within 1 year of diagnosis, and 55% of the sample
      received at least 1 nonrecommended imaging service for surveillance purposes.
      Seventy-seven percent of the sample received at least 1 nonrecommended biomarker
      test. Regression results indicate that main treating physician, advanced disease
      stage, younger age at diagnosis, and greater number of years since diagnosis were
      associated with receiving nonrecommended services for surveillance. CONCLUSIONS:
      Use of nonrecommended services for surveillance occurs frequently among early
      stage breast cancer survivors. There are opportunities to increase use of
      guideline concordant posttreatment care for breast cancer survivors.

PMID- 24105103
TI  - Bioequivalence studies for 2 different strengths of
      irbesartan/hydrochlorothiazide combination in healthy volunteers: 300/25 mg and
      300/12.5 mg film-coated tablets.
AB  - Two bioequivalence studies of irbesartan (CAS 138402-11-6) and
      hydrochlorothiazide (CAS 58-93-5) combination at 300/12.5 mg and 300/25 mg
      strengths were carried out in order to assess the bioequivalence of these film
      coated tablet formulations in comparison with the marketed reference
      formulations.Both studies were performed with 30 healthy volunteers according to
      an open label, randomized, 2-period, 2-sequence, crossover, single dose and
      fasting conditions design. In each study, test and reference formulations were
      administered in 2 treatment days, separated by a washout period of 7 days. Blood
      samples were drawn up to 72 h following drug administration in case of irbesartan
      and up to 24 h in case of hydrochlorothiazide. Plasma concentrations of both
      analytes were obtained by a validated HPLC method using MS/MS detection. Log
      transformed AUC0-t and Cmax values were tested for bioequivalence based on the
      ratios of the geometric LSmeans (test/reference).For both studies, the 90%
      confidence intervals of the geometric LSmean values for the test/reference ratios
      for AUC0-t [(irbesartan: 300/12.5 mgstrength: 95.33-111.74%. 300/25 mg strength:
      91.27-103.93%) (hydrochlorothiazide: 300/12.5 mg strength: 99.63-107.50%. 300/25
      mg strength: 95.72-102.24%)] and Cmax [(irbesartan: 300/12.5 mg strength: 98.73
      115.03%. 300/25 mg strength: 97.27-112.12%) (hydrochlorothiazide: 300/12.5 mg
      strength: 97.34-112.06%. 300/25 mg strength: 93.29-106.38%)] were within the bio
      equivalence acceptance range of 80-125%.According to the European Guideline on
      the Investigation of Bioequivalence it may be therefore concluded that both test
      formulations are bioequivalent to the corresponding reference formulations.
      Overall, it was judged that both studies were conducted with a good tolerance of
      the subjects to study drugs. 

PMID- 24105104
TI  - Combined inhibition of PDE4 and PI3Kdelta modulates the inflammatory component
      involved in the progression of chronic obstructive pulmonary disease.
AB  - Chronic Obstructive Pulmonary Disease (COPD) represents a group of disorders with
      several underlying causes that hamper airflow into the lungs. Despite current
      intervention therapies, COPD remains a disease with a significant unmet medical
      need. Treatment with Phosphodiesterase (PDE) 4 inhibitors results in modest
      efficacy at clinically relevant doses. The objective of the current study is to
      evaluate the combination of a PDE4 (Roflumilast) and a Phosphoinositide-3-kinase
      (PI3K) delta (IC87114) inhibitor for their therapeutic potential in diminishing
      the inflammatory response associated with COPD. Due to their divergent and
      independent pathways, we hypothesize that the combination would be efficacious at
      low concentrations in an in vitro setting. Inhibition of TNFalpha, pAkt, MMP-9 in
      differentiated U937 macrophages upon stimulation with LPS/CSE was determined.
      Neutrophil functionality manifested by a modulation of elastase activity was
      estimated. Protective effect of drug combination on CSE induced apoptosis of lung
      epithelial cells was also determined. Data demonstrated that the combination of
      Roflumilast and IC87114 reduced TNFalpha, pAkt and MMP-9 at nanomolar
      concentrations and was several fold potent than either of the compounds alone.
      Inhibition of neutrophil elastase was also increased significantly with the
      combination along with a better protection against CSE induced apoptosis in
      alveolar epithelial cells, thereby providing a rationale for their evaluation in
      COPD patients. 

PMID- 24105105
TI  - Effect of cyanocobalamin (vitamin B12) in the induction and expression of
      morphine tolerance and dependence in mice.
AB  - The antinociceptive effect of cyanocobalamin (Vit B12) has been reported in
      animal models and human studies. Our previous study showed the effect of Vit B12
      on morphine tolerance. The dependence and tolerance were induced in male mice
      using subcutaneous morphine injections, 3 times a day (50, 50 and 75 mg/kg/day)
      for 3 days. Mice also received Vit B12 (100, 250 and 500 ug/kg), clonidine,
      memantine and saline intraperitoneally before morphine administration. On fourth
      day mice received only 7 mg /kg morphine just before tail-flick test. To
      determine the expression of morphine dependence and tolerance, all compounds were
      injected once intraperitoneally on the day of experiment. The tolerance was
      evaluated by the tail-flick test. The effect of Vit B12 and other agents on
      dependence were evaluated by counting the number of jumps (induced by naloxone 5
      mg/kg). Co-administration of Vit B12 (100-500 ug/kg) and morphine in 3 days
      reduced the development of tolerance to morphine analgesic effect (8.2+/-0.5 and
      7.83+/-0.5 s. vs. normal saline, 3.57+/-0.3 s). Repeated administration of Vit
      B12, also, diminished the reduced naloxane withdrawal signs of naloxone
      withdrawal test (100-500 ug/kg: 5+/-1.9 and 1.2+/-0.8 jumps vs. normal saline
      72.6+/-12.2). However, Vit B12 had no effect on the expression of morphine
      tolerance and physical dependence. It is concluded that co-administration of Vit
      B12 and morphine could reduce tolerance to analgesic effect of morphine chronic
      administration and also reduce its withdrawal symptoms. 

PMID- 24105106
TI  - Pharmacokinetics, safety and tolerability of triflusal and its main active
      metabolite HTB in healthy Chinese subjects.
AB  - Triflusal presents comparable antiplatelet activity to aspirin while presenting a
      more favourable safety profile, and is used in the treatment of thrombosis. The
      study aimed to evaluate the pharmacokinetics and safety of triflusal and its
      major metabolite 2-(hydroxyl)-4-(trifluoromethyl)- benzoic acid (HTB) in healthy
      Chinese subjects.30 healthy subjects were recruited in this randomized, single
      center, and open-label, parallel, single ascending doses (300, 600, 900 mg) and
      multiple doses (600 mg, once daily for 7 days) study. Plasma samples were
      analyzed with a validated liquid chromatography tandem mass spectrometry
      (LC/MS/MS) method. Safety was assessed by adverse events, ECG, laboratory
      testing, and vital signs.Triflusal was safe and well tolerated. After single-dose
      administration, triflusal was rapidly absorbed with a mean Tmax of 0.55-0.92 h
      and a mean t1/2 kel of 0.35-0.65 h, HTB was absorbed with a mean Tmax of 2.35
      3.03 h and a mean t1/2 kel of 52.5-65.57 h. Cmax and AUC for triflusal and HTB
      were approximately dose proportional over the 300-900 mg dose range. In the
      steady state, the accumulation index (R) indicated that the exposure of triflusal
      increased slightly with repeated dosing, and the exposure of HTB increased
      obviously. 3 adverse events certainly related to the investigational drugs
      occurred in the multiple-dose phase.Following oral dosing under fasting
      condition, triflusal is promptly absorbed and rapidly depleted from the systemic
      circulation. HTB is quickly generated from triflusal and slowly eliminated.
      Triflusal accumulates slightly in the body. HTB plasma concentration builds up
      progressively toward steady-state. 

PMID- 24105108
TI  - [Total aortic arch replacement for severe atherosclerotic aortic
      aneurysms;consecutive 135 cases study].
AB  - OBJECTIVE: We study the validity of surgical procedure for total aortic arch
      replacement according to the atherosclerosis in the aortic arch. METHODS: From
      2007 to June 2013, Consecutive 185 patients underwent total aortic arch
      replacement for thoracic aortic anuerysm. We studied 135 patients[96 males 72.1
      year(38~89year)]except emergency operation. We assessed the atherosclerosis in
      the aortic arch by preoperative enhanced computed tomography (CT)scan and
      intraoperative epiaortic echocardiography. Based on the degree of atherosclerosis
      in the aortic arch, we divided into 2 groups:group 1(G1)included 97 patients with
      mild or moderate atherosclerosis and group 2 (G2) 38 patients with severe
      atherosclerosis. We used ascending aorta as arterial cannulation site in G1 and
      axillary artery with 8 mm graft in G2 .We compared with both groups for
      preoperative comorbidities and outcomes( mortality and stroke). RESULTS: Three
      patients died in the hospital (2%). In-hospital neurological events occurred in
      12 patients, including major stroke in 4 patients, minor stroke in 4 patients and
      asymptomatic convulsion in 4 patients, although they were transient and clear
      before discharge except major stroke. There were no statistically significant
      differences in preoperative characteristics, cardiopulmonary bypass, brain
      protection, mortality, and neurological events between the 2 groups. There was a
      statistically difference in operation time( 388.8 minutes vs 448.5 minutes,
      p<0.01), intensive care unit( ICU) stay( 3.1 day vs 6.5 days, p<0.05) and
      hospital stay( 19.2 days vs 28.0 days, p<0.05). CONCLUSIONS: We selected surgical
      procedure for total aortic arch replacement (TAR) according to atherosclerosis in
      the aortic arch. Although the rate of stroke was largely acceptable, we much need
      to be improved in prevention of stroke.

PMID- 24105107
TI  - Fluorogenic small molecules requiring reaction with a specific protein to create
      a fluorescent conjugate for biological imaging--what we know and what we need to
      learn.
AB  - We seek fluorogenic small molecules that generate a fluorescent conjugate signal
      if and only if they react with a given protein-of-interest (i.e., small molecules
      for which noncovalent binding to the protein-of-interest is insufficient to
      generate fluorescence). Consequently, it is the new chemical entity afforded by
      the generally irreversible reaction between the small molecule and the protein-of
      interest that enables the energy of an electron occupying the lowest unoccupied
      molecular orbital (LUMO) of the chromophore to be given off as a photon instead
      of being dissipated by nonradiative mechanisms in complex biological
      environments. This category of fluorogenic small molecules is created by starting
      with environmentally sensitive fluorophores that are modified by an essential
      functional group that efficiently quenches the fluorescence until a
      chemoselective reaction between that functional group and the protein-of-interest
      occurs, yielding the fluorescent conjugate. Fluorogenic small molecules are
      envisioned to be useful for a wide variety of applications, including live cell
      imaging without the requirement for washing steps and pulse-chase kinetic
      analyses of protein synthesis, trafficking, degradation, etc.

PMID- 24105109
TI  - [Brain protection during operation for aortic arch aneurysms].
AB  - Aortic arch replacement has been safely performed by moderate hypothermic
      circulatory arrest, and antegrade selective cerebral perfusion. To prevent
      permanent neurological deficit, it is important to precisely evaluate brain, neck
      vessels and atherosclerotic thoracic aorta by computed tomography(CT), magnetic
      resonance imaging (MRI)and intraoperative epiaortic echography, which can lead
      the safest cannulation site, careful manipulation of cerebral perfusion
      catheters. It is also important to make good exposure of surgical site,
      especially in distal anastomosis, and irrigate and flush atheromatous debris.
      Since 1991 to 2013, our consecutive 410 cases of total and hemi arch replacement
      of aorta, including 57 emergency cases, result in 22 cases( 5.4%) of mortality(
      3.1% of elective, 19.3% of emergency) and 10 cases( 2.4%) of stroke( 2.3% of
      elective, 3.5% of emergency). Mortality and morbidities are more likely be
      occurred in emergency cases. It is possible to keep good operative results with
      reliable brain protection of selective antegrade cerebral perfusion which gives
      enough time for secure open distal anastomosis to every surgeon, but
      atheroemborism from shaggy aorta remains as a problem yet to be solved. 

PMID- 24105110
TI  - [Surgical strategy for extended aortic arch aneurysm].
AB  - The management of an extended aortic arch aneurysm still remains a clinical
      challenge. Open surgery can be invasive for the patients with comorbidities.
      Since thoracic endovascular aneurysm repair (TEVAR) was introduced, hybrid
      therapy has been applied for the extended arch aneurysm. From 1997 to 2013, 379
      patients have undergone aortic arch surgery. Of those, 241 patients of non
      dissection aneurysm were studied. Open surgical repair with L-shaped thoracotomy
      was done in 28 patients, frozen elephant trunk( FET) in 30 patients, long
      elephant trunk( LET) with 2nd TEVAR in 21 patients, debranched TEVAR in 10
      patients and standard arch grafting in 152 patients as a control group. The brain
      infarction rate was high in debranched TEVAR (40%) and L-shaped group (25%). The
      paraplegia rate was high in FET group( 23.3%). The respiratory failure rate was
      high in the L-shaped group and the LET group. In-hospital mortality was 0.0% in
      the L-shaped group, 6.7% in the FET group, 4.8% in the LET group, 20% in the
      debranched group and 0.7% in the control group. The debranched TEVAR group is our
      early experience, and the recent outcomes of this procedure have improved. The
      management of extended aortic arch aneurysm has changed with hybrid approach
      combined with TEVAR. Open repair is still the gold standard, but hybrid therapy
      is used for high-risk patients. Off-pump debranched TEVAR tends to be applied for
      extended arch aneurysm. 

PMID- 24105111
TI  - [Outcomes after total arch replacement using antegrade selective cerebral
      perfusion under right axillary artery perfusion].
AB  - Although the outcomes of total arch replacement have been improving, the
      prevention of cerebral infarction is still an important consideration in aortic
      arch surgery. Herein, we reviewed our experience with total arch replacement
      using antegrade selective cerebral perfusion under right axillary artery
      perfusion. Between January 2002 and March 2013, total arch replacement was
      performed for 125 patients including 31 patients with acute aortic dissection. An
      8 mm polyester grafts was sutured to the axillary artery through the right
      subclavicular incision and was connected to cardiopulmonary bypass circuit.
      Antegrade selective cerebral perfusion under hypothermic circulatory arrest was
      initiated using right axillary artery perfusion. Postoperative cerebral
      infarction occurred in 5.6% of patients. Hospital mortality rate was 3.2%. The 5
      year rate of freedom from aortic event was 83%. The 5-year survival rate was 75%.
      We consider that right axillary artery perfusion is advantageous for preventing
      cerebral infarction in total arch replacement. 

PMID- 24105112
TI  - [Total aortic arch replacement;our current surgical management and outcomes].
AB  - OBJECTIVE: We report our current surgical management and early and late outcomes
      of total arch replacement. METHOD: From October 1999 to December 2012, 372
      consecutive patients (mean age 71.8+/-12.0) underwent total arch replacement
      through a median sternotomy at our institute. Mean Japan score (predicted 30 day
      mortality) was 8.0+/-9.2( median 4.4). Our current surgical approach included the
      following:(1) meticulous selection of arterial cannulation site and type of
      arterial cannula;(2) circulatory arrest at tympanic temperature (below 23 
      degrees C) and rectal temperature (below 30  degrees C);(3) antegrade selective
      cerebral perfusion and cerebral monitoring of regional cerebral saturation;(4)
      early rewarming just after distal anastomosis;(5)maintaining fluid balance below
      1,000 ml during cardiopulmonary bypass. RESULTS: Overall 30 day and in-hospital
      mortality was 1.6%( 6/372) and 3.8%( 14/372), and was 1.0%(3/308)and 2.6% (8/308)
      in elective cases. Permanent neurologic deficit occurred in 2.2%(8/372) of
      patients. The mean follow up period were46+/-39months(range2~165 months).
      Survival at 5 and 10 years after surgery was 75.8+/-2.8% and 66.0+/-3.8%,
      respectively. During follow up period, there was only one total arch replacement
      related problem (proximal anastomosis aneurysm). Freedom from additional aortic
      surgery and aortic related event at 5 and 10 years was 90.8 +/-2.2% and 86.1+/
      3.4%,respectively. CONCLUSION: Our current approach for total aortic arch
      replacement was associated with low hospital mortality and morbidities and with
      favorable long-term outcome.

PMID- 24105113
TI  - [Recent outcomes of open total arch repair using selective cerebral perfusion
      with some technical improvement].
AB  - OBJECTIVE: Recently, some technical improvements in aortic arch repair have
      brought better outcomes. In this article, we reviewed our surgical results of
      open arch repair using selective cerebral perfusion(SCP). METHODS: Between 2001
      and 2012, a total of 813 patients (median age of 70 years) underwent total arch
      replacement with SCP. We preferably use the right axillary artery cannulation for
      SCP and stepwise technique for distal anastomosis. The temperature at hypothermic
      circulatory arrest was moder ate in 46%, and deep in 54%.Of them, 22% had
      emergency surgery. RESULTS: Early mortality was 5.2% in all. The incidences of
      permanent( PND) and temporary neurological deficits were 3.4% and 7.3%. No spinal
      cord injury occurred, even with moderate hypothermia. The cumulative survival
      rates were 78.4% and 49.9% at 5 and 10 years, respectively. The freedom from arch
      reoperation was 98.0% and 96.2% at 5 and 10 years, respectively. CONCLUSIONS:
      Open total arch replacement using selective cerebral perfusion with some
      technical improvement provides favorable outcome, even in long-term period.

PMID- 24105114
TI  - [Long-term results of open stent-grafting applied with a Matsui-Kitamura( MK)
      stent in treatment of arch aneurysm].
AB  - We report the initial and long-term results of open stent-grafting (OSG) applied
      with a Matsui-Kitamura (MK) stent in the treatment of thoracic aortic aneurysm
      (TAA). From August 2005 to March 2013, OSG for TAA was applied in 46 cases(
      male/female, 36/10, 54-86 years old, mean age 71). During deep hypothermic
      circulatory arrest with antegrade selective cerebral perfusion, stent graft was
      delivered through the transected proximal aortic arch, followed by arch
      replacement with a 4-branched prosthesis. Operative mortality within 30 days was
      6.5%(respiratory failure in 1, multiple organ failure in 1and ischemic enteritis
      in 1) and there was 1 in hospital death due to brain stem infarction.
      Perioperative morbidity included 2( 4.3%) stroke, 5( 10.9%) spinal cord injuries(
      paraplegia in 1, paraparesis in 1 and transient paraparesis in 3). In long-term
      follow-up, survival was 86.8%, 77.2%, and 72.0% for 1, 3 and 5 years. Freedom
      from aortic event was 97.3%, 93.8% and 89.1% for 1, 3 and 5 years. Theseresults
      suggested the OSG method applied with a MK stent is a useful surgical procedure
      for the treatment of TAA. 

PMID- 24105115
TI  - [Total debranching through mini-sternotomy].
AB  - Aneurysms of the aortic arch are technically challenging to repair with thoracic
      endovascular aneurysm repair (TEVAR). Various optional techniques such as
      debranching or hybrid TEVAR enable landing zones to extend, however, there is
      still room for improvement. We have performed total debranching to facilitate
      TEVAR with adequate central neck length more than 2.5 cm. In summary our
      procedure has 3 features:mini-thoracotomy to minimize its surgical stress which
      might cause post-operative respiratory failure, side-to-side anastomosis of
      trifurcated graft with ascending aorta to avoid its kinking after chest closure,
      and the usage of Pruitt-Inahara shunt tube during anastomoses of the carotid
      artery. 

PMID- 24105116
TI  - [Pulmonary resection in renal cell carcinoma metastasis;the influence of
      histologic atypia of the metastatic focus on preoperative or perioperative
      diagnosis].
AB  - The diagnostic potential of histological atypia grades in distinguishing between
      primary lung tumors and renal pulmonary metastases. OBJECTIVE: In cases of
      pulmonary resection for renal cell carcinoma patients, both the preoperative and
      perioperative diagnosis of lung cancer may be complicated by the need to
      distinguish between a primary lung tumor and metastatic renal tumor. The degree
      of histological atypia (grade) of the suspected metastatic focus may indicate the
      source of the lesion. The aim of this study was to evaluate the preoperative and
      perioperative diagnostic potential of histological atypia in determining the
      origin of lung tumors. STUDY DESIGN: Five cases that involved surgery for
      suspected lung metastasis from renal cell carcinoma were investigated. RESULTS:
      In cases for which the precise diagnosis of the metastatic focus was uncertain,
      histological atypia of the metastatic focus was of grade 3, whereas that of the
      primary renal cancer was of grade 1 or 2. CONCLUSION: These findings suggest that
      lung metastases with grade 3 histological atypia are suspected to be primary lung
      tumors on the basis of preoperative imaging, and preoperative distinction between
      primary lung tumors and metastases from renal cell carcinoma is therefore
      difficult. In such cases, the choice of operative method needs to be very
      carefully considered.

PMID- 24105117
TI  - [Long-term survival case of primitive neuroectodermal tumor in the chest wall of
      a young adult].
AB  - A very rare case of Askin's tumor is described. A 22-year-old male was admitted
      to our hospital because of an abnormal shadow on chest roentgenogram. His chest X
      ray film showed a tumor shadow (4.0*5.0 cm) of chest wall protruding into the
      upper right lung field. The tumor shadow had markedly enlarged in size compared
      to previous examinations of chest X-ray film 1 month before. Chest computed
      tomography(CT) and magnetic resonance imaging( MRI) revealed an heterogenous
      tumor fixed on the right 4th rib, which did not infiltrate the surrounding
      tissues. In the examination of bone scintigram, no abnormal accumulation was seen
      at the site of the chest wall tumor. Because of the possibility of malignancy, an
      en bloc excision of the tumor was performed including the surrounding pleura. The
      histologic examination revealed primitive neuroectodermal tumors of the chest
      wall (Askin's tumor).The patient underwent both additional adjuvant chemotherapy
      and radiation therapy postoperatively, being alive and well without any sign of
      recurrence 10 years after the operation. Askin's tumor is a very rare disease
      with an extremely poor prognosis, however, the effective treatment has not been
      established yet. Complete excision at initial operation seemed to be correlated
      with long-term survival in this case. 

PMID- 24105118
TI  - [Spontaneous tension hemothorax due to rupture of a solitary fibrous tumor of the
      posterior mediastinum].
AB  - A 37-year-old man was transported by ambulance to our hospital due to abrupt
      chest pain. The pain began when he was practicing a combative-type sport. He
      denied any impact or blunt trauma. A chest radiograph revealed massive left
      pleural effusion with a mediastinal shift. Thoracentesis revealed a
      hemothorax;therefore, we performed an emergency thoracotomy. The intraoperative
      findings revealed a rupture of a posterior mediastinal tumor itself located
      between the descending aorta and the thoracic vertebra. After we identified the
      artery of Adamkiewicz that originates away from the tumor and evaluated the
      degree of tumor extension into the inter-vertebral foramen, we safely performed
      an elective tumor resection 1 month after the initial emergency operation. In
      patients with a hemothorax caused by rupture of the tumor itself, an elective
      tumor resection after detailed investigation should be considered if hemostasis
      can be achieved in the emergency thoracotomy. 

PMID- 24105119
TI  - [Empyema from spontaneous esophageal rupture treated by thoracoscopic surgery].
AB  - A 61-year-old man who had been admitted for vomiting and abdominal pain 5 days
      before at another hospital was transferred to our hospital. He was diagnosed as
      pyo-pneumothorax, and chest drainage was initiated. Seven days after admission,
      food residue was observed in the drainage tube. A subsequent gastrointestinal
      fiberscopic examination could not identify the esophageal injury, but the acute
      empyema caused by spontaneous esophageal rupture was suggested by clinical signs.
      Thoracoscopic surgery for curettage and irrigation of the pleural cavity was
      performed. Esophageal rupture could not be confirmed at surgery. Spontaneous
      closure of the fistula was observed 2 weeks post-surgery. 

PMID- 24105120
TI  - [Surgery for benign schwannoma arising at the thoracic apex].
AB  - It is difficult to determine surgical approaches for treating a tumor arising at
      the thoracic outlet. Here we report a case of benign schwannoma arising at the
      thoracic apex, in which both pleural and cervical approaches were adopted. Chest
      radiographs of a 58-year-old male at the medical checkup in 2009 showed a tumor
      shadow in the right apical region that was increasing since 2003. He had no
      symptoms. Computed tomography(CT)and magnetic resonance imaging (MRI) showed a 35
      mm tumor, which had a smooth surface and was suspected as a neurogenic tumor
      arising at the right thoracic outlet. Surgery for this tumor was performed by the
      thoracoscopic approach with a mini thoracotomy through the 3 intercostal space 1.
      The tumor was suspected to arise from the brachial plexus, and was not able to be
      enucleated. Then we made a cervical incision and the tumor was resected safely
      using a pleural approach together with a cervical approach. The pathological
      finding was benign shwannoma. Mild ulnar nerve palsy was observed in the patient
      after surgery, which gradually improved within 3 years. 

PMID- 24105121
TI  - [Rapid growth of peripheral lung lipoma;report of a case].
AB  - Peripheral lung lipoma is extremity rare entity. To date 13 English literature
      and 5 Japanese cases including our case were published since Buchman's 1st report
      in 1911. A 53 year-old man was sent to our hospital with 2.5 cm lung mass
      detected on chest X-ray by annual health check. Computed tomography(CT)scan
      revealed homogenous fat density mass which was thought benign tumor, however,
      because of rapid growth lung mass which has not been detected on chest X-ray 1
      year before, surgery was inevitable choice for diagnosis. On operative findings,
      lung adhesion and many vessels were seen around the mass. These facts suggested
      some possibility of the relationship between inflammation and the occurrence,
      growth of lipoma. We present a rare case of peripheral lung lipoma with rapid
      growth pattern. 

PMID- 24105122
TI  - [Schwannoma of the chest wall showing a bead-like appearance;report of a case].
AB  - A 35-year-old man with a chest abnormal shadow was referred to our hospital.
      Computed tomography(CT) revealed a bead-like shaped mass along the right 7th rib.
      The lesion appeared to have 2 narrow parts and was divided into 3 round portions.
      T2-weighted images of the magnetic resonance imaging(MRI) revealed marked
      hyperintensity in the peripheral portions and nodule-like intermediate signal
      intensity in one of the central zone of the round portions, which is so-called
      "target appearance". The bead-like mass with 3 round portions revealed to be a
      mass of the right 7th intercostal nerve. The tumor was diagnosed as benign
      schwannoma of mixed Antoni type A and type B histologically. 

PMID- 24105123
TI  - The relationship between typhoons' peripheral circulation and ground-level ozone
      concentrations in central Taiwan.
AB  - Surface data of meteorological parameters (wind speed, wind direction, and mixing
      height) and air pollutant concentrations (O3, NO, and NO2) were collected for a
      92-day period associated with typhoon formation in 2005. The influence of
      typhoons on O3 concentration were defined by azimuth and distance from Taiwan,
      and Types A, B, and C correspond to typhoons less than 1,500 km from Taiwan and
      located between azimuths 45 degrees  and 135 degrees , 135 degrees  and 225
      degrees , and 225 degrees  and 45 degrees , respectively. Type D corresponds to
      typhoons more than 1,500 km from Taiwan. Titration reactions were conducted at
      three temporal phases: 2000-0700, 0800-1100, and 1200-1400 LST (Local Standard
      Time). The air pollution model (TAPM) was used to simulate wind fields and
      trajectories of air masses. It was determined that typhoon position affected O3
      concentration, temporal and spatial patterns of O3 titration and vertical
      meteorological characteristics, which were not all at the statistically
      significant level. 

PMID- 24105125
TI  - Monitoring water quality in Sydney Harbour using blue mussels during remediation
      of the Sydney Tar Ponds, Nova Scotia, Canada.
AB  - Using mussels as monitoring tools we measured water quality in Sydney Harbour
      during a large scale, multi-year remediation project of the Sydney Tar Ponds
      (STPs); one of Canada's most contaminated sites. Chemical contaminants were
      measured in blue mussels (Mytilus edulis) in Sydney Harbour, which were used as
      monitoring tools to assess the spatio-temporal distribution of polycyclic
      aromatic hydrocarbons (PAHs); polychlorinated biphenyls (PCBs); metals (As, Cd,
      Cu, Hg, Pb, Zn) and lipid content during baseline and 3 years of remediation. The
      overall spatio-temporal distribution of chemicals in mussels was also compared to
      contaminants in other marine indicators (e.g., sediment, water and crab tissue).
      Measured metal concentrations in mussels showed some minor temporal variability
      (4 years), but these did not appear to be directly related to remediation
      activities, with the highest concentrations of As, Hg and Zn measured at
      reference stations. Most measured contaminants showed stable or potentially
      decreasing concentrations during the study, except Pb and Zn. Individual PAH
      compounds were mostly undetected during baseline and remediation, except for
      fluoranthene and pyrene. Concentrations of fluoranthene in mussels and deep water
      samples were moderately related. Generally, PCBs were undetected (<0.05 MUg g(
      1)), except during year 2 remediation at some near-field stations. Contaminants
      measured during this study were at much lower concentrations than previously
      reported in other studies of mussels in Sydney Harbour and eastern Canada. This
      is likely due to the ongoing natural recovery of Sydney Harbour and to a lesser
      extent because of the environmental mitigation protection measures implemented
      during remediation activities at the STPs. The lack of detection of most
      individual PAHs and PCBs, plus relatively low bio-accumulation of metals observed
      during baseline and remediation attest to the effectiveness of using mussels as
      monitoring tools for environmental quality. 

PMID- 24105124
TI  - Biomonitoring of polycyclic aromatic hydrocarbons in urban and industrial
      environments of the Western Black Sea Region, Turkey.
AB  - This research was carried out in the cities of Zonguldak and Eregli, which have
      been characterized as urban and industrial environments of the Western Black Sea
      Region, Turkey, in order to assess the contamination of polycyclic aromatic
      hydrocarbons (PAHs) using mosses as biomonitors. The methodology involved the
      collection of moss samples (Hypnum cupressiforme), ultrasonic extraction with
      dichloromethane, cleanup using silica gel and analysis by liquid chromatography
      with ultraviolet detection. The total PAH concentrations ranged from 78.1 to
      1693.5 ng g(-1) in Zonguldak and from 15.2 to 275.1 ng g(-1) in Eregli. The total
      PAH concentration in Eregli was about six times lower than that in Zonguldak,
      revealing the importance of switching from coal to natural gas in residential
      heating. The diagnostic ratios and the correlation analysis have indicated that
      coal combustion and traffic emissions were the major PAH sources at both sites.
      The contour maps were constructed for the determination of spatial distributions
      of total PAHs, and it was shown for Zonguldak as well as for Eregli that the PAH
      pollution was much more predominant in highly populated regions. Moving away from
      the city centres, a gradual decrease in PAH pollution rates was observed. 

PMID- 24105249
TI  - Antibacterial properties of 2% lidocaine and reduced rate of endophthalmitis
      after intravitreal injection.
AB  - PURPOSE: To determine whether the application of subconjunctival 2%
      lidocaine/0.1% methylparaben for anesthesia may reduce rates of endophthalmitis
      after intravitreal (IVT) injection. METHODS: We performed in vitro experiments to
      determine the antibacterial properties of 2% lidocaine/0.1% methylparaben
      (lidocaine) against causative organisms of endophthalmitis. Isolates of
      Staphylococcus aureus, Staphylococcus epidermidis, and Streptococcus viridans
      from patients with endophthalmitis were incubated with or without lidocaine.
      Aliquots (100 uL) were plated on Mueller-Hinton (S. aureus and S. epidermidis) or
      blood agar plates (S. viridans) at 0, 10, 30, 120, and 240 minutes, and colonies
      were counted after 24 hours. A retrospective review of 15,042 IVT injections was
      performed from January 2004 to February 2011 to determine the rate of
      endophthalmitis with or without application of subconjunctival lidocaine for
      anesthesia. RESULTS: Lidocaine demonstrated rapid bactericidal effects against
      all 3 organisms. After 10 minutes of exposure, there was approximately a 90% (P <
      0.01), 95% (P < 0.001), and 92% (P < 0.001) reduction in colony forming units
      when compared with time 0 for S. aureus, S. epidermidis, and S. viridans,
      respectively. Complete elimination of colony forming units occurred at subsequent
      time points for each organism in contrast to logarithmic increase for control
      plates. There were a total of 0 cases of endophthalmitis of 6,853 IVT injections
      performed with subconjunctival lidocaine and 8 cases of endophthalmitis of 8,189
      (0.1%) IVT injections performed with other methods of anesthesia (P = 0.03).
      CONCLUSION: Application of subconjunctival 2% lidocaine/0.1% methylparaben for
      anesthesia may reduce the incidence of endophthalmitis after IVT injection.

PMID- 24105250
TI  - Long-term high-fat consumption leads to downregulation of Akt phosphorylation of
      eNOS at Ser1177 and upregulation of Sirtuin-1 expression in rat cavernous tissue.
AB  - Long-term consumption of high-fat diets negatively interferes with metabolic
      status and promotes endothelial dysfunction and inflammation. In the cavernous
      tissue, these outcomes become conspicuous in the elderly and strongly affect
      penile erection, a vascular process highly dependent on local nitric oxide
      bioavailability. Although epidemiological data links erectile dysfunction to
      nutritional patterns, the underlying molecular mechanisms remain unclear.
      Therefore, we investigated the effects of long-term high-fat diet on endothelial
      nitric oxide synthase (eNOS)-Sirtuin-1 axis and Akt/eNOS phosphorylation in the
      cavernous tissue of Sprague-Dawley rats, and compared with energy-restricted
      animals. We demonstrated that high-fat diet intake led to a noteworthy decrease
      in eNOS phosphorylation at Ser1177 residue through the Akt pathway, which seems
      to be compensated by upregulation of phosphorylation at Ser615, but without an
      increment in nitric oxide production. These results are accompanied by an
      increase of systemic inflammatory markers and upregulation of the inducible NOS
      and of the deacetylase Sirtuin-1 in the cavernous tissue to levels apparently
      detrimental to cells and to metabolic homeostasis. Conversely, in long-term
      energy-restricted animals, the rate of phosphorylation of eNOS at Ser1177
      diminished, but the activation of the enzyme increased through phosphorylation of
      eNOS at Ser615, resulting in an enhancement in nitric oxide bioavailability.
      Taken together, our results demonstrate that long-term nutritional conditions
      override the influence of age on the eNOS expression and activation in rat
      cavernous tissue. 

PMID- 24105251
TI  - Three-Tesla dynamic contrast-enhanced MRI: a critical assessment of its use for
      differentiation of renal lesion subtypes.
AB  - PURPOSE: To evaluate the ability of dynamic contrast-enhanced (DCE) 3-T MRI for
      preoperative differentiation between benign and malignant renal tumors and RCC
      subtypes. METHODS: Sixty consecutive patients undergoing preoperative DCE 3-T MRI
      of the kidney were evaluated in this retrospective IRB-approved evaluation. Fifty
      four malignant tumors and 17 benign tumors upon surgical verification were
      included. Relative enhancement values of complete lesions and the most enhancing
      part of the lesions (hotspot) were measured using four repetitions: precontrast,
      arterial, venous, and delayed. RESULTS: Mean relative enhancement patterns
      between malignant and benign lesions did not differ significantly during any
      postcontrast phase (p > 0.05). The highest mean enhancement during all
      postcontrast phases was identified in clear cell RCC followed by chromophobic
      RCC. The enhancement pattern in papillary RCC was significantly less than that of
      non-papillary RCC lesions. Arterial enhancement was an independent predictor for
      RCC subtypes (papillary vs. non-papillary, p = 0.008). The diagnostic accuracy
      for differentiation of papillary from non-papillary RCC based on ROC analysis was
      76.4% [95% CI 62.2-87.2%]; p < 0.0001. CONCLUSIONS: Dynamic contrast-enhanced MRI
      at 3 T showed intermediate diagnostic capability for differentiation between
      papillary and non-papillary RCC subtypes but could not differentiate between
      benign and malignant renal lesions.

PMID- 24105252
TI  - Pharmacokinetic comparisons of bepotastine besilate and bepotastine salicylate in
      healthy subjects.
AB  - BACKGROUND AND OBJECTIVE: Bepotastine is a second-generation histamine H(1)
      receptor antagonist that is indicated in allergic rhinitis, urticaria, and
      pruritus associated with skin disease. The aim of the present study was to
      compare the pharmacokinetics of two different bepotastine formulations
      [bepotastine besilate 10 mg (reference) and bepotastine salicylate 9.64 mg
      (test)], both containing 7.11 mg bepotastine base, to satisfy regulatory
      requirements for marketing. METHODS: A single-center, randomized, single-dose,
      open-label, two-period, two-sequence crossover study with a 7-day washout period
      was conducted in 26 healthy male subjects. Plasma samples for drug analysis were
      collected up to 24 h after drug treatment. Pharmacokinetic parameters, including
      maximum plasma concentration (C(max)) and area under the plasma concentration
      time curve (AUC), were calculated. ANOVA for bioequivalence was conducted using
      log-transformed C(max) and AUC values, and the mean ratios and their 90 %
      confidence intervals were calculated. RESULTS: Of the 26 participants initially
      enrolled, 24 healthy participants completed both treatment periods. All
      pharmacokinetic parameters of bepotastine exhibited no significant differences
      between the two formulations. The observed mean (standard deviation) C(max), AUC
      from time zero to the time of the last measurable concentration (AUC(last)), and
      AUC from time zero to infinity (AUC(infinity)) values for the reference
      formulation were 99.9 (31.4) ng/mL, 388.9 (102.6) ng.h/mL, and 392.4 (103.6)
      ng.h/mL, respectively. Corresponding values for the test formulation were 101.0
      (26.3) ng/mL, 389.8 (112.2) ng.h/mL, and 393.7 (111.7) ng.h/mL. The geometric
      mean ratios (90 % CI) between the two formulations were 1.0220 (0.9224-1.1324)
      for C(max), 0.9928 (0.9521-1.0351) for AUC(last), and 0.9959 (0.9549-1.0387) for
      AUC(infinity). During the study period, two adverse events were reported in the
      test formulation group, but both were transient, mild, and resolved completely
      during the treatment period. These adverse events were considered unrelated to
      the study drugs. CONCLUSION: The results of the present study revealed that
      bepotastine besilate 10 mg (reference) and bepotastine salicylate 9.64 mg (test)
      formulations have comparable pharmacokinetic characteristics and that these two
      formulations meet the regulatory criteria for bioequivalence. Both bepotastine
      formulations were generally well-tolerated in this population.

PMID- 24105253
TI  - Residual activity after radioembolization of liver tumours with 90Y resin
      microspheres. A safe calculation method.
AB  - The actual number of resin microspheres is approximately 30-60 times higher than
      glass microspheres per 3 GBq vial. Thus, radioembolization (RE) with resin
      microspheres exerts an embolization effect besides the radiation effect. This
      embolization effect can occasionally cause early back flow of the microspheres
      before application of the entire calculated dose. To avoid these adverse side
      effects, RE has to be terminated at an earlier time point. Measurement of the
      residual activity in the delivery box, which includes the v-vial, tube and
      catheter, to calculate the achieved target dose is often challenging. The aim of
      the current study was to establish a post-RE measurement method comparable to the
      glass microspheres method without unnecessary radiation exposure to the staff and
      risk of contamination. METHODS: Two different measurements were performed. First,
      total radioactivity in the shipping vial was measured in an ion chamber and then
      it was put in the delivery box and the radiation was measured from a 30 cm
      distance from the centre of the box with a dosimeter. The required radioactivity
      was then transferred to the v-vial, and the shipping vial was measured again.
      After that, the v-vial was measured from the same distance from the centre of the
      box with dosimeter. RESULTS: Altogether 62 times the shipping vial with different
      activities were measured with a significant positive correlation between the
      amount of the activity measured in the iron chamber and the radiation dose,
      measured with dosimeter (r2 = 0.98; p< 0.001). There was also a strong positive
      correlation between these measurements of the v-vial (r2 = 0.98; p< 0.001).
      CONCLUSION: With measurement of the residual activity in the delivery box using a
      dosimeter the percentage of the whole injected activity can be easily calculated.
      This facilitates the calculation of the actual, achieved target and non-target
      dose in those cases, where therapy had to be stopped because of eminent flow
      reversal or obstruction.

PMID- 24105254
TI  - Therapeutic effect and risk factors for complications of excision in 76 patients
      with schwannoma.
AB  - BACKGROUND: Benign schwannoma is the most common tumor of peripheral nerves.
      However, the clinical course of excision and risk factors associated with
      postoperative neurological deficits are not well known. We evaluated the
      incidence of preoperative symptoms, the incidence of postoperative neurological
      deficits, and the risk factors of neurological deficits. METHODS: We
      retrospectively reviewed data of 76 patients with schwannomas treated at our
      institution. We reviewed the clinical characteristics, and postoperative results,
      and determined the possible risk factors influencing the development of
      complications. RESULTS: Excision of schwannoma improved the Tinel-like signs in
      47 of 51 patients and spontaneous pain in 14 of 15. Eleven of 17 patients with
      sensory deficits showed complete recovery, but six continued to show deficits
      with or without improvement. Motor deficits that were observed in four patients
      persisted in one. New neurological deficits developed in 21 patients and
      persisted until final follow-up in 8. Tinel-like signs was the risk factor of
      surgery-related neurological deficits (p = 0.009). CONCLUSIONS: New deficits
      developed predominantly in patients with preoperative Tinel-like signs. Attention
      should be given to patients with the factor.

PMID- 24105255
TI  - Three-coordinate gold(I) N-heterocyclic carbene complexes: a new class of
      strongly luminescent derivatives.
AB  - A selected group of cationic three-coordinate Au(I)-NHC complexes of the form
      [Au(NHC)(dppbz)]OTf have been prepared from a commercially available bidentate
      phosphine. All complexes have been fully characterised by NMR and mass
      spectroscopy. The [Au(NHC)](+) fragment shows a pronounced tendency to form
      linear complexes which is confirmed by the molecular structure of
      [Au(IPr)(dppbz)]OTf in the solid state. The complexes are brightly luminescent
      and present very high quantum yield values in the solid state. The assignments of
      the electronic transitions involved in the emissions are of a phosphorescent
      nature and it is proposed that the origin of the emissions is derived from the
      ligand (dppbz) to metal-ligand (Au-NHC) charge-transfer (LML'CT) transition.

PMID- 24105256
TI  - Vaporisation and thermal decomposition of dialkylimidazolium halide ion ionic
      liquids.
AB  - Vaporisation and liquid phase thermal decomposition, TD, of two halide ion ionic
      liquids, 1-octyl-3-methylimidazolium chloride, [C8C1Im]Cl, and 1-octyl-3
      methylimidazolium iodide, [C8C1Im]I, are investigated using temperature
      programmed desorption (TPD) line of sight mass spectrometry (LOSMS) at ultra-high
      vacuum (UHV). The ability to use MS to distinguish between vaporisation and TD
      allows the thermodynamics/kinetics of both vaporisation and TD to be investigated
      within the same experiments. Vaporisation of both halide ion ionic liquids is
      demonstrated. For both [C8C1Im]Cl and [C8C1Im]I the vapour is shown to be
      composed of neutral ion pairs (NIPs). The enthalpy of vaporisation at temperature
      T, DeltavapHT, was experimentally determined as DeltavapH455 = 151 +/- 10 kJ mol(
      1) for [C8C1Im]Cl and DeltavapH480 = 149 +/- 8 kJ mol(-1) for [C8C1Im]I.
      Extrapolation of DeltavapHT to the reference temperature, 298 K, gave
      DeltavapH298 = 166 +/- 10 kJ mol(-1) for [C8C1Im]Cl and DeltavapH298 = 167 +/- 8
      kJ mol(-1) for [C8C1Im]I, higher than most DeltavapH298 values measured to date
      for other [C8C1Im](+)-containing ionic liquids. In addition, predictions of
      DeltavapH298 for other halide ion ionic liquids are made. Liquid phase TD is
      shown to proceed via nucleophilic substitution to give two sets of products: 1
      octylimidazole and methylhalide, and 1-methylimidazole and 1-octylhalide. The
      activation energy of TD at a temperature T, Ea,TD,T, is measured for the
      nucleophilic substitution of [C8C1Im]I to give methyliodide; Ea,TD,480 = 136 +/-
      15 kJ mol(-1). Ea,TD,T is measured for the nucleophilic substitution of
      [C8C1Im]Cl to give methylchloride; Ea,TD,455 = 132 +/- 10 kJ mol(-1). The fact
      that DeltavapHT and Ea,TD,T are the same (within error) for both ionic liquids is
      commented upon, and conclusions are drawn as to the thermal stability of these
      ionic liquids. 

PMID- 24105258
TI  - Biomarker-driven therapeutic management of Alzheimer's disease: establishing the
      foundations.
AB  - Biomarkers are characteristics that are objectively measured and evaluated as
      indicators of normal biological processes, pathogenic processes, or pharmacologic
      responses to a therapeutic intervention. Amyloid measures become abnormal early
      in the Alzheimer's disease process and have only weak correlations with disease
      progression and cognitive decline; cerebrospinal fluid tau, brain atrophy, and
      reduced cortical metabolism correlate with cognitive measures and disease
      progression. Combinations of biomarkers have higher correlations and are better
      predictors of future decline than single biomarkers. Current biomarkers do not
      account for all of the variance in Alzheimer's disease; a more complete
      repertoire of biomarkers that more comprehensively assay the disease process is
      needed.

PMID- 24105259
TI  - Abuse, danger, and security in transnational marriages: polity and community in
      India and the United Kingdom.
AB  - The aim of this article is to show the way in which concepts of abuse, danger,
      and security have informed recent U.K. legal and policy developments relating to
      the protection of women in transnational marriages from violence within families
      and communities. It also demonstrates the way in which the same concepts inform
      debates on violence against women in families in India to provide a greater
      understanding of the interaction between "polity" and "community" in
      transnational marriages. 

PMID- 24105257
TI  - Antiobesity pharmacotherapy: new drugs and emerging targets.
AB  - Obesity is a growing pandemic, and related health and economic costs are
      staggering. Pharmacotherapy, partnered with lifestyle modifications, forms the
      core of current strategies to reduce the burden of this disease and its sequelae.
      However, therapies targeting weight loss have a significant history of safety
      risks, including cardiovascular and psychiatric events. Here, evolving strategies
      for developing antiobesity therapies, including targets, mechanisms, and
      developmental status, are highlighted. Progress in this field is underscored by
      Belviq (lorcaserin) and Qsymia (phentermine/topiramate), the first agents in more
      than 10 years to achieve regulatory approval for chronic weight management in
      obese patients. On the horizon, novel insights into metabolism and energy
      homeostasis reveal guanosine 3',5'-cyclic monophosphate (cGMP) signaling circuits
      as emerging targets for antiobesity pharmacotherapy. These innovations in
      molecular discovery may elegantly align with practical off-the-shelf approaches,
      leveraging existing approved drugs that modulate cGMP levels for the management
      of obesity.

PMID- 24105260
TI  - Membrane driven spatial organization of GPCRs.
AB  - Spatial organization of G-protein coupled receptors (GPCRs) into dimers and
      higher order oligomers has been demonstrated in vitro and in vivo. The
      pharmacological readout was shown to depend on the specific interfaces, but why
      particular regions of the GPCR structure are involved, and how ligand-determined
      states change them remains unknown. Here we show why protein-membrane hydrophobic
      matching is attained upon oligomerization at specific interfaces from an analysis
      of coarse-grained molecular dynamics simulations of the spontaneous diffusion
      interaction of the prototypical beta2-adrenergic (beta2AR) receptors in a POPC
      lipid bilayer. The energy penalty from mismatch is significantly reduced in the
      spontaneously emerging oligomeric arrays, making the spatial organization of the
      GPCRs dependent on the pattern of mismatch in the monomer. This mismatch pattern
      is very different for beta2AR compared to the highly homologous and structurally
      similar beta1AR, consonant with experimentally observed oligomerization patterns
      of beta2AR and beta1AR. The results provide a mechanistic understanding of the
      structural context of oligomerization. 

PMID- 24105261
TI  - Courtship feeding in humans? The effects of feeding versus providing food on
      perceived attraction and intimacy.
AB  - Food sharing may be used for mate attraction, sexual access, or mate retention in
      humans, as in many other species. Adult humans tend to perceive more intimacy in
      a couple if feeding is observed, but the increased perceived intimacy may be due
      to resource provisioning rather than feeding per se. To address this issue, 210
      university students (66 male) watched five short videos, each showing a different
      mixed-sex pair of adults dining together and including feeding or simple
      provisioning or no food sharing. A survey concerning attraction and intimacy in
      the dyad was completed after each video. Both provisioning and feeding produced
      higher ratings of "Involvement," with feeding producing the highest ratings.
      Similarly, the perceived attraction of each actor to the other was lowest when no
      food sharing was shown and highest when feeding was displayed. These findings are
      consistent with a view of feeding as a courtship display in humans. 

PMID- 24105262
TI  - Analysis of ESCRT functions in exosome biogenesis, composition and secretion
      highlights the heterogeneity of extracellular vesicles.
AB  - Exosomes are extracellular vesicles (EVs) secreted upon fusion of endosomal
      multivesicular bodies (MVBs) with the plasma membrane. The mechanisms involved in
      their biogenesis have not yet been fully identified although they could be used
      to modulate exosome formation and therefore are a promising tool in understanding
      exosome functions. We have performed an RNA interference screen targeting 23
      components of the endosomal sorting complex required for transport (ESCRT)
      machinery and associated proteins in MHC class II (MHC II)-expressing HeLa-CIITA
      cells. Silencing of HRS, STAM1 or TSG101 reduced the secretion of EV-associated
      CD63 and MHC II but each gene altered differently the size and/or protein
      composition of secreted EVs, as quantified by immuno-electron microscopy. By
      contrast, depletion of VPS4B augmented this secretion while not altering the
      features of EVs. For several other ESCRT subunits, it was not possible to draw
      any conclusions about their involvement in exosome biogenesis from the screen.
      Interestingly, silencing of ALIX increased MHC II exosomal secretion, as a result
      of an overall increase in intracellular MHC II protein and mRNA levels. In human
      dendritic cells (DCs), ALIX depletion also increased MHC II in the cells, but not
      in the released CD63-positive EVs. Such differences could be attributed to a
      greater heterogeneity in size, and higher MHC II and lower CD63 levels in
      vesicles recovered from DCs as compared with HeLa-CIITA. The results reveal a
      role for selected ESCRT components and accessory proteins in exosome secretion
      and composition by HeLa-CIITA. They also highlight biogenetic differences in
      vesicles secreted by a tumour cell line and primary DCs.

PMID- 24105263
TI  - STARD3 or STARD3NL and VAP form a novel molecular tether between late endosomes
      and the ER.
AB  - Inter-organelle membrane contacts sites (MCSs) are specific subcellular regions
      favoring the exchange of metabolites and information. We investigated the
      potential role of the late-endosomal membrane-anchored proteins StAR related
      lipid transfer domain-3 (STARD3) and STARD3 N-terminal like (STARD3NL) in the
      formation of MCSs involving late-endosomes (LEs). We demonstrate that both STARD3
      and STARD3NL create MCSs between LEs and the endoplasmic reticulum (ER). STARD3
      and STARD3NL use a conserved two phenylalanines in an acidic tract (FFAT)-motif
      to interact with ER-anchored VAP proteins. Together, they form an LE-ER tethering
      complex allowing heterologous membrane apposition. This LE-ER tethering complex
      affects organelle dynamics by altering the formation of endosomal tubules. An in
      situ proximity ligation assay between STARD3, STARD3NL and VAP proteins
      identified endogenous LE-ER MCS. Thus, we report here the identification of
      proteins involved in inter-organellar interaction. 

PMID- 24105264
TI  - The cilium-like region of the Drosophila spermatocyte: an emerging flagellum?
AB  - Primary cilia and flagella are distinct structures with different functions in
      eukaryotic cells. Despite the fact that they share similar basic organization and
      architecture, a direct developmental continuity among them has not been reported
      until now. The primary cilium is a dynamic structure that typically assembles and
      disassembles during mitotic cell cycles, whereas the sperm axoneme is nucleated
      by the centriole inherited by the differentiating spermatid at the end of
      meiosis. Fruit flies display a remarkable exception to this general rule.
      Drosophila spermatocytes have an unusual axoneme-based structure reminiscent of
      primary cilia (the cilium-like region, or CLR). This structure persists through
      the meiotic divisions when it is internalized with the centriole to organize the
      centrosome and is finally inherited by young spermatids. Examination of
      elongating spermatids by transmission electron microscopy (EM) and cold regrowth
      experiments suggests that the motile axoneme derives directly from the elongation
      and remodelling of the immotile CLR. Both the CLR and elongating spermatid
      flagella have incomplete C-tubules that form longitudinal sheets associated with
      the B-tubule wall, unlike axonemes of other organisms in which C-tubules stop
      growing at the transition between the basal body and the axonemal doublets.
      Moreover, both the CLR and spermatid flagella lack a structured transition zone,
      a characteristic feature of ciliated cells. Uncoordinated (unc) mutants that lack
      C-remnants have short centrioles, suggesting that the C-sheets play a role in the
      elongation of the centriole after it docks to the cell membrane. The structural
      similarities between CLR and sperm axoneme suggest that the CLR can be considered
      as the basal region of the future axoneme and could represent the start point for
      its elongation. 

PMID- 24105265
TI  - Short transmembrane domains with high-volume exoplasmic halves determine
      retention of Type II membrane proteins in the Golgi complex.
AB  - It is still unclear why some proteins that travel along the secretory pathway are
      retained in the Golgi complex whereas others make their way to the plasma
      membrane. Recent bioinformatic analyses on a large number of single-spanning
      membrane proteins support the hypothesis that specific features of the
      transmembrane domain (TMD) are relevant to the sorting of these proteins to
      particular organelles. Here we experimentally test this hypothesis for Golgi and
      plasma membrane proteins. Using the Golgi SNARE protein Sft1 and the plasma
      membrane SNARE protein Sso1 from Saccharomyces cerevisiae as model proteins, we
      modified the length of their TMDs and the volume of their exoplasmic hemi-TMD,
      and determined their subcellular localization both in yeast and mammalian cells.
      We found that short TMDs with high-volume exoplasmic hemi-TMDs confer Golgi
      membrane residence, whereas TMDs with low-volume exoplasmic hemi-TMDs, either
      short or long, confer plasma membrane residence to these proteins. Results
      indicate that the shape of the exoplasmic hemi-TMD, in addition to the length of
      the entire TMD, determine retention in the Golgi or exit to the plasma membrane
      of Type II membrane proteins. 

PMID- 24105267
TI  - Smad2 and Smad3 cooperate and antagonize simultaneously in vertebrate
      neurogenesis.
AB  - The transforming growth factor beta (TGF-beta) pathway plays key roles in
      development and cancer. TGF-beta signaling converges on the Smad2 and Smad3
      effectors, which can either cooperate or antagonize to regulate their
      transcriptional targets. Here we performed in vivo and in silico experiments to
      study how such cooperativity and antagonism might function during neurogenesis.
      In vivo electroporation experiments in the chick embryo neural tube show that
      Smad2 and Smad3 cooperate to promote neurogenesis, as well as the transcription
      of Smad3-specific targets. Knockdown of Smad2 enhances neurogenesis and the
      transcription of Smad3-specific targets. A mathematical model of the TGF-beta
      pathway fits the experimental results and predicts that the proportions of the
      three different trimeric complexes formed dictates the transcriptional responses
      of the R-Smad proteins. As such, Smad2 targets are activated solely by the Smad2
      Smad2-Smad4 complex, whereas Smad3 targets are activated both by Smad2-Smad3
      Smad4 and Smad3-Smad3-Smad4 trimers. We have modeled the Smad responses onto
      arbitrary genes and propose that this mechanism might be extended to additional
      activities of TGF-beta in development and disease. 

PMID- 24105266
TI  - Glycosylation of closely spaced acceptor sites in human glycoproteins.
AB  - Asparagine-linked glycosylation of proteins by the oligosaccharyltransferase
      (OST) occurs when acceptor sites or sequons (N-x?P-T/S) on nascent polypeptides
      enter the lumen of the rough endoplasmic reticulum. Metazoan organisms assemble
      two isoforms of the OST that have different catalytic subunits (STT3A or STT3B)
      and partially non-overlapping cellular roles. Potential glycosylation sites move
      past the STT3A complex, which is associated with the translocation channel, at
      the protein synthesis elongation rate. Here, we investigated whether close
      spacing between acceptor sites in a nascent protein promotes site skipping by the
      STT3A complex. Biosynthetic analysis of four human glycoproteins revealed that
      closely spaced sites are efficiently glycosylated by an STT3B-independent process
      unless the sequons contain non-optimal sequence features, including extreme close
      spacing between sequons (e.g. NxTNxT) or the presence of paired NxS sequons (e.g.
      NxSANxS). Many, but not all, glycosylation sites that are skipped by the STT3A
      complex can be glycosylated by the STT3B complex. Analysis of a murine
      glycoprotein database revealed that closely spaced sequons are surprisingly
      common, and are enriched for paired NxT sites when the gap between sequons is
      less than three residues.

PMID- 24105268
TI  - Predicting the type of hearing loss using click auditory brainstem response in
      babies referred from newborn hearing screening.
AB  - OBJECTIVES: This study examined the ability of click auditory brainstem response
      (ABR) undertaken below the age of 6 months (from expected date of delivery) to
      differentiate between conductive and sensorineural hearing loss (SNHL), using the
      latency of wave V measured 20 dB above threshold. DESIGN: Subjects were recruited
      if they had an ABR threshold of >= 40 dB nHL and <= 70 dB nHL in one or both ears
      measured below the age of 6 months and they had also attended follow-up
      appointments for behavioral assessment of their hearing in which the type of
      hearing loss had been confirmed. Forty-five children (84 ears) with SNHL, 82
      children (141 ears) with temporary conductive hearing loss (TCHL), and 5 children
      (10 ears) with permanent conductive hearing loss (PCHL) were recruited. The
      differences between mean wave V latencies measured 20 dB above ABR threshold were
      examined using the independent t-test for the groups of cases with SNHL, TCHL,
      and PCHL. Signal-detection theory was used to examine the relationship between
      sensitivity and specificity when the latency of wave V 20 dB above threshold was
      used to identify the presence of SNHL. Receiver operating characteristics were
      generated and the coordinates of the curve examined for the best compromise
      between sensitivity and false-alarm rate. The specificity, positive predictive
      value, and probability of missing a true case were determined for the most
      promising criteria. RESULTS: There were significant differences between the two
      groups with SNHL and TCHL. The mean latency of wave V 20 dB above threshold was 1
      msec shorter in those with SNHL compared with those with TCHL. There were
      significant differences between children with PCHL and SNHL but no difference
      between those with PCHL and TCHL. When a criterion of < 7.6 msec was chosen to
      predict the presence of SNHL the test sensitivity was 0.98, test specificity
      0.71, and positive predictive value was 0.66. Nine out of 10 of those with a
      latency 20 dB above threshold of < 7.0 msec had an SNHL. CONCLUSIONS: The latency
      of wave V 20 dB above threshold measured using click ABR is a useful indicator of
      the type of hearing loss in babies referred from newborn hearing screening.

PMID- 24105269
TI  - Acceptance and practicability of a visual communication tool in smoking cessation
      counselling: a randomised controlled trial.
AB  - BACKGROUND: Smoking cessation advice is important for reducing the worldwide
      burden of disease resulting from tobacco smoking. Appropriate risk communication
      formats improve the success of counselling interventions in primary care. AIMS:
      To test the feasibility and acceptance of a smoking cessation counselling tool
      with different cardiovascular risk communication formats including graphs, in
      comparison with the International Primary Care Respiratory Group (IPCRG) 'quit
      smoking assistance' tool. METHODS: GPs were randomised into an intervention group
      (using our communication tool in addition to the IPCRG sheet) and a control group
      (using the IPCRG sheet only). We asked participants for socioeconomic data,
      smoking patterns, understanding of information, motivation, acceptance and
      feasibility, and measured the duration and frequency of counselling sessions.
      RESULTS: Twenty-five GPs performed 2.8 counselling sessions per month in the
      intervention group and 1.7 in the control group (p=0.3) with 114 patients. The
      median duration of a session was 10 mins (control group 11 mins, p=0.09 for
      difference). Median patients' motivation for smoking cessation was 7 on a 10
      point visual analogue scale with no significant difference before and after the
      intervention (p=0.2) or between groups (p=0.73 before and p=0.15 after the
      intervention). Median patients' ratings of motivation, selfconfidence,
      understanding of information, and satisfaction with the counselling were 3-5 on a
      5-point Likert scale, similar to GPs' ratings of acceptance and feasibility, with
      no significant difference between groups. CONCLUSIONS: Among Swiss GPs and
      patients, both our innovative communication tool and the IPCRG tool were well
      accepted and both merit further dissemination and application in research.

PMID- 24105270
TI  - Lactobacillus plantarum HY7712 protects against the impairment of NK-cell
      activity caused by whole-body gamma-irradiation in mice.
AB  - While searching for lactic acid bacteria that can restore aging-impaired immune
      responses, we isolated the Toll-like receptor (TLR) 2/NF-kappaB-activating strain
      Lactobacillus plantarum HY7712 from kimchi and investigated its immunomodulating
      effect in whole-body gamma-irradiated mice. Exposure to HY7712 strongly activated
      NF-kappaB signaling in RAW264.7 cells, but inhibited lipopolysaccharide
      stimulated NF-kappaB activation. Moreover, HY7712 protected against the
      downregulation of interferon (IFN)-gamma and upregulation of interleukin (IL)-13
      caused by gamma-irradiation in mice. In mice, gamma-irradiation impaired NK-cell
      activity against YAC-1 tumor cells, but following HY7712 exposure, the activity
      of NK cells was restored to 91.5% of the level measured in control mice (p <
      0.05). These findings suggest that HY7712 activates the TLR2/NF-kappaB signaling
      pathway and protects against the impairment of NK-cell activity caused by gamma
      irradiation or aging.

PMID- 24105271
TI  - Comparative proteomic analyses of synovial fluids and serums from rheumatoid
      arthritis patients.
AB  - Rheumatoid arthritis (RA) is a chronic and systemic inflammatory disorder that
      primarily affects the flexible joints and may also affect a number of tissues and
      organs. The progression of RA involves an inflammatory response of the capsule
      around the joint, swelling of synovial cells with excess synovial fluid (SF), and
      the development of fibrous tissue in the synovium. Since the progressive
      pathology of the disease often leads to the irreversible destruction of articular
      cartilage and ankylosis of the joint, early diagnosis of RA is essential. Thus,
      we undertook a comparative proteomic approach to investigate novel biomarkers for
      early diagnosis using SFs and serums from RA patients. As a result, we identified
      32 differentially expressed spots in SFs and 34 spots in serums. The differential
      expression of the STEAP4 and ZNF 658 proteins were validated using immunoblotting
      of the SFs and serums, respectively. These data suggest that differentially
      expressed proteins in SFs and serums could be used as RA-specific biomarkers for
      the diagnosis and monitoring of RA. Furthermore, these findings advance our
      understanding of the molecular etiopathogenesis of RA. 

PMID- 24105272
TI  - Decreased expression of SERPINB1 correlates with tumor invasion and poor
      prognosis in hepatocellular carcinoma.
AB  - SERPINB1 (serine protease inhibitor, clade B, member1) is a member of the SERPINB
      family. Recent studies suggested that SERPINB1 may suppress the migration and
      invasion of lung and breast cancers. In this study, we investigated a possible
      involvement of SERPINB1 in the regulation of hepatocellular carcinoma metastasis
      (HCC). The expression of SERPINB1 was evaluated using western blot analysis in 8
      paired fresh HCC specimens and immunohistochemistrical assay on 67 paraffin
      embedded HCC slices. SERPINB1 was downregulated in HCC specimens and
      correlatively related with two clinicopathologic features of HCC, metastasis (P =
      0.000) and vein invasion (P = 0.006). Univariate and multivariate survival
      analyses showed a lower level of SERPINB1 expression is associated with poor
      prognosis and clinical outcome (P = 0.001). In addition, small interfering RNA
      targeting SERPINB1 was used to knock down the expression of SERPINB1 in Huh7 and
      BEL-7404 cells. We showed that interference of SERPINB1 promoted migration and
      invasion of HCC cells, while cell proliferation was not affected. Finally, we
      observed an apparent increase in the level of active matrix metalloproteinase-2
      (MMP2) after SERPINB1 knockdown, implying that SERPINB1 might participate in the
      regulation of HCC metastasis through modulating the activation of matrix
      metalloproteinases. Overall, our results suggested an inhibitory role of SERPINB1
      in the migration and invasion of HCC, implying that SERPINB1 might be a potential
      prognostic indicator of HCC metastasis. 

PMID- 24105273
TI  - The genetic causes of convergent evolution.
AB  - The evolution of phenotypic similarities between species, known as convergence,
      illustrates that populations can respond predictably to ecological challenges.
      Convergence often results from similar genetic changes, which can emerge in two
      ways: the evolution of similar or identical mutations in independent lineages,
      which is termed parallel evolution; and the evolution in independent lineages of
      alleles that are shared among populations, which I call collateral genetic
      evolution. Evidence for parallel and collateral evolution has been found in many
      taxa, and an emerging hypothesis is that they result from the fact that mutations
      in some genetic targets minimize pleiotropic effects while simultaneously
      maximizing adaptation. If this proves correct, then the molecular changes
      underlying adaptation might be more predictable than has been appreciated
      previously. 

PMID- 24105276
TI  - Evolution: Speciation goes with the flow.

PMID- 24105274
TI  - Mutations in regulators of the epigenome and their connections to global
      chromatin patterns in cancer.
AB  - Malignancies are characterized by extensive global reprogramming of epigenetic
      patterns, including gains or losses in DNA methylation and changes to histone
      marks. Furthermore, high-resolution genome-sequencing efforts have discovered a
      wealth of mutations in genes encoding epigenetic regulators that have roles as
      'writers', 'readers' or 'editors' of DNA methylation and/or chromatin states. In
      this Review, we discuss how these mutations have the potential to deregulate
      hundreds of targeted genes genome wide. Elucidating these networks of epigenetic
      factors will provide mechanistic understanding of the interplay between genetic
      and epigenetic alterations, and will inform novel therapeutic strategies. 

PMID- 24105275
TI  - Advanced genetic tools for plant biotechnology.
AB  - Basic research has provided a much better understanding of the genetic networks
      and regulatory hierarchies in plants. To meet the challenges of agriculture, we
      must be able to rapidly translate this knowledge into generating improved plants.
      Therefore, in this Review, we discuss advanced tools that are currently available
      for use in plant biotechnology to produce new products in plants and to generate
      plants with new functions. These tools include synthetic promoters, 'tunable'
      transcription factors, genome-editing tools and site-specific recombinases. We
      also review some tools with the potential to enable crop improvement, such as
      methods for the assembly and synthesis of large DNA molecules, plant
      transformation with linked multigenes and plant artificial chromosomes. These
      genetic technologies should be integrated to realize their potential for
      applications to pressing agricultural and environmental problems. 

PMID- 24105277
TI  - Rebiopsy of non-small cell lung cancer patients with acquired resistance to
      epidermal growth factor receptor-tyrosine kinase inhibitor: Comparison between
      T790M mutation-positive and mutation-negative populations.
AB  - BACKGROUND: The secondary epidermal growth factor receptor (EGFR) mutation
      Thr790Met (T790M) accounts for approximately half of acquired resistances to EGFR
      tyrosine kinase inhibitor (TKI). Recent reports have demonstrated that the
      emergence of T790M predicts a favorable prognosis and indolent progression.
      However, rebiopsy to confirm T790M status can be challenging due to limited
      tissue availability and procedural feasibility, and little is known regarding the
      differences among patients with or without T790M mutation. METHODS: The study
      investigated 78 EGFR-mutant patients who had undergone rebiopsy after TKI
      failure. The peptide nucleic acid-locked nucleic acid polymerase chain reaction
      clamp method was used in EGFR mutational analyses. Various patient
      characteristics and postprogression survivals (PPSs) after initial TKI failure
      were retrospectively compared in patients with and without T790M. RESULTS: The
      T790M mutation was identified in 4 (17%) of 24 central nervous system lesions,
      and in 22 (41%) of 54 other lesions (P = .0417). No other characteristics had a
      statistical association with T790M prevalence. Median PPS was 31.4 months in 26
      patients with T790M, and 11.4 months in 52 patients without T790M (P = .0017). In
      the multivariate analysis, statistically significant factors for longer PPS
      included T790M-positive, good performance status, and no carcinomatous
      meningitis. CONCLUSIONS: The emergence of T790M in central nervous system lesions
      was rare, compared with other lesions. Patients with T790M after TKI failure
      appear to have better prognoses than those without T790M. TKI rechallenge or
      continuous administration beyond progression may be effective after initial TKI
      failure.

PMID- 24105278
TI  - A synopsis of techniques for paraesophageal hernia repair: different approaches
      to current controversies.

PMID- 24105279
TI  - Laparoscopic paraesophageal hernia repair.
AB  - The last 2 decades have witnessed a revolution in the treatment of patients with
      paraesophageal hernia (PEH). Nowadays, the laparoscopic repair with
      fundoplication is considered as the primary treatment modality in most academic
      centers for symptomatic patients. Three findings have clearly emerged: (1) this
      procedure is technically demanding; (2) it is associated with relief of symptoms
      in most patients; and (3) most recurrences are small and asymptomatic. This
      article describes our approach step-by-step to the repair of a paraesophageal
      hiatal hernia, focusing on several technical controversies. 

PMID- 24105280
TI  - Laparoscopic paraesophageal hernia repair: critical steps and adjunct techniques
      to minimize recurrence.
AB  - INTRODUCTION: Laparoscopic repair of paraesophageal hernias (PEH) is associated
      with a high objective hernia recurrence rate. Tension is a key factor in the
      repair of any hernia, and tension is a cause for hernia recurrence. METHODS: This
      is a review of my current technique for PEH repair, and represents the
      culmination of years of experience and modifications in an effort to minimize
      objective hernia recurrence rates in my own practice. RESULTS: There are 4
      critical steps that must be part of every PEH repair in my opinion. These are
      excision of the hernia sac, mediastinal esophageal mobilization, crural repair,
      and fundoplication. Tension on the repair comes in the form of axial tension
      related to esophageal shortening and lateral tension related to widely splayed
      crura. Axial tension is addressed with a Collis gastroplasty, while lateral
      tension requires a right, left, or bilateral crural relaxing incision. The crura
      should not be bridged with mesh, rather a relaxing incision allows primary crural
      approximation even with very splayed crura. The primary crural closure is
      routinely reinforced with absorbable mesh. Follow-up with upper endoscopy or
      videoesophagram shows a low recurrence rate using these 4 steps and the adjunct
      techniques to reduce tension when necessary. DISCUSSION: Efforts to reduce the
      objective recurrence rate after laparoscopic PEH repair should focus on
      minimizing tension with the use of a Collis gastroplasty and crural relaxing
      incisions when necessary. Similar to hernias at other sites, the use of mesh
      likely is another adjunct step that will improve outcomes with PEH repair, but to
      avoid erosion synthetic mesh should be avoided.

PMID- 24105281
TI  - Laparoscopic paraesophageal hernia repair.
AB  - Repair of the large paraesophageal hernias-types II, III, and IV is a challenging
      surgical problem. There are many technical modifications to the numerous aspects
      of surgical repair. The 2 most critical aspects of repair are: (1) aggressive
      mobilization of the esophagus to restore and ensure length and (2) the
      underestimated and understudied technique of hiatal closure. We describe the
      techniques and unique modifications such as a combined Hill and Nissen repair
      utilized at Swedish Medical Center There remains considerable opportunity through
      research and surgical innovation to improve on existing techniques in the repair
      of the paraesophageal hernia. 

PMID- 24105282
TI  - Laparoscopic paraesophageal hernia repair: current controversies.
AB  - The advent of laparoscopy has significantly improved postoperative outcomes in
      patients undergoing surgical repair of a paraesophageal hernia. Although this
      minimally invasive approach considerably reduces postoperative pain and recovery
      times, and may improve physiologic outcomes, laparoscopic paraesophageal hernia
      repair remains a complex operation requiring advanced laparoscopic skills and
      experience with the anatomy of the gastroesophageal junction and diaphragmatic
      hiatus. In this article, we describe our approach to patient selection,
      preoperative evaluation, operative technique, and postoperative management.
      Specific attention is paid to performing an adequate hiatal dissection and
      esophageal mobilization, the decision of whether to use a mesh to reinforce the
      crural repair, and construction of an adequate antireflux barrier (ie,
      fundoplication). 

PMID- 24105283
TI  - Laparoscopic paraesophageal hernia repair.
AB  - Laparoscopic paraesophageal hernia repair is an operation that allows for relief
      of gastrointestinal and respiratory symptoms with a minimal recovery time and a
      high degree of satisfaction. It is a difficult and complex operation; however, if
      the important tenets are adhered to by surgeons with a lot of experience in
      laparoscopic PEH repair, the results are good. Patient selection is important.
      Older or frail patients who are asymptomatic should not have an operation, and
      some who are very symptomatic should probably consider just a reduction of their
      gastric volvulus and gastropexy. Still, most of the patients will be symptomatic
      and will be able to tolerate a laparoscopic definitive repair. The important
      aspects of repair include: complete resection of the hernia sac from the
      mediastinum, adequate esophageal mobilization, adequate closure of the hiatus,
      and fundoplication. The most troublesome aspect of the operation is the
      recurrence rate, which is up to 50% at 5 years of follow-up. Fortunately, most
      recurrences are asymptomatic and the vast majority of patients still have greatly
      improved quality of life. 

PMID- 24105284
TI  - Postoperative Dysphagia in laparoscopic paraesophageal hernia repair: the effect
      of distal esophageal angulation.
AB  - BACKGROUND: Dysphagia following laparoscopic paraesophageal hernia repair is an
      uncommon but difficult problem that may be due to technical factors. We looked
      for an association between esophageal angulation after posterior crural repair
      and postoperative dysphagia. MATERIALS AND METHODS: Patients undergoing
      paraesophageal hiatus hernia repair were identified from a prospectively
      maintained dedicated database. All patients underwent a standardized laparoscopic
      repair. Essentially the hernia sac was dissected from the mediastinum, a
      posterior hiatal repair was carried out with interrupted polyester sutures, and
      augmented with mesh on lay. A partial posterior fundoplication was then carried
      out. We used the number of posterior sutures as a proxy for anterior esophageal
      angulation. Quality-of-life data and dysphagia scores were recorded
      preoperatively, at 6 weeks postoperatively and 12 months postoperatively using
      validated instruments. RESULTS: Between November 2004 and September 2010, 114
      consecutive patients underwent paraesophageal hiatus hernia repair. There was 1
      postoperative death in the series. Median age was 67 years (interquartile range,
      59 to 77 y) and 90 (79%) were female. Median hospital stay was 3 days
      (interquartile range, 2 to 5 y). Follow-up data were available in 87 (76%) of
      patients at 6 weeks and 94 (82%) of patients at 12 months postoperation. Overall,
      there was a significant improvement in quality of life that was sustained out to
      12 months (P<0.001). Dakkak dysphagia scores were significantly improved
      postoperatively. Improvement was sustained out to 12 months (P<0.001). Three
      patients underwent endoscopic esophageal dilation for dysphagia following
      surgery. There was no significant correlation between the number of posterior
      sutures used and dysphagia outcome. Specifically there was no association with
      overall Dakkak scores or change in Dakkak score. CONCLUSIONS: Anterior angulation
      due to posterior hiatal repair does not result in worsening dysphagia, even in
      patients with large hiatal defects. A posterior repair should therefore remain
      the standard approach for hiatal closure.

PMID- 24105285
TI  - Endoscopic treatment of biliary fistulas developing after liver resections.
AB  - Bile leaks are a major cause of mortality and morbidity after liver resections.
      We prospectively evaluated the safety and efficacy of endoscopic treatment of
      biliary fistulas developing after liver resections in 15 patients. Fistulas
      developed after extended right hepatectomy in 4, extended left hepatectomy in 8,
      and segmentectomy in 3 patients. Median time interval between surgery and
      endoscopic intervention was 10 days (range, 7 to 35 d). Endoscopic sphincterotomy
      followed by a nasobiliary drain insertion was the initial treatment. If the
      fistula persisted after 2 weeks, nasobiliary drain was replaced by a plastic
      stent. The effect of output (low in 10 and high in 5 patients) and the origin of
      fistula (stump in 10 and resection surface of the liver in 5 patients) on the
      time for closure were evaluated. Bile leakage ceased by only nasobiliary drainage
      catheter placement in 11 patients (73.3%). Plastic stents were inserted in 4
      patients. There was a significant correlation between the output of bile leakage
      and the time needed for fistula closure. Endoscopic treatment methods are
      effective in patients with bile leaks due to liver resections. 

PMID- 24105286
TI  - The "lost anvil": an original technique for laparoscopic colorectal anastomosis.
AB  - AIM: During laparoscopic colorectal anastomosis, the rectal introduction of the
      circular stapler is achieved without hand assistance, increasing the risk of
      rectal injury. Therefore, we describe a technical adjustment facilitating rectal
      advancement of the stapler. MATERIALS AND METHODS: Two hundred consecutive
      patients with benign condition underwent laparoscopic sigmoidectomy. Before any
      stapling, the complete circular stapler is introduced into the anus. The anvil is
      released in the lumen of the colon to be resected. After cross-stapling the
      rectum, the anvil is retrieved in the resected specimen before the final steps of
      the anastomosis. Feasibility, safety, and long-term results were evaluated.
      RESULTS: In 194 patients, the anastomosis was successfully performed at upper
      rectal level. Only, 1 rectal wall injury was observed. At a median follow-up of
      44 months, 3 patients presented anastomotic stenosis and 2 small-bowel
      obstructions. CONCLUSIONS: "Lost anvil" technique allows easy and safe circular
      stapler rectal advancement for laparoscopic colorectal anastomosis in benign
      diseases.

PMID- 24105287
TI  - Plastic freezer bags: a cost-effective method to protect extraction sites in
      laparoscopic colorectal procedures?
AB  - PURPOSE: To review surgical-site infection (SSI) and retrieval-site tumor
      recurrence rates in laparoscopic colorectal procedures when using a plastic
      freezer bag as a wound protector. METHODS: Laparoscopic colorectal procedures
      where a plastic freezer bag used as a wound protector at the extraction site were
      reviewed between 1991 and 2008 from a prospectively collected database. chi test
      was used to compare SSI and tumor recurrence rates between groups. Costing data
      were obtained from the operating room supplies department. RESULTS: A total of
      936 cases with 51 (5.45%) surgical-site infections were identified. SSI rates did
      not differ when comparing groups based on demographic factors, diagnosis, or
      location of procedure. Retrieval-site tumor recurrence rate was 0.21% (1/474).
      Cost of plastic freezer bags including sterilization ranged from $0.25 to $3.
      CONCLUSIONS: Plastic freezer bags as wound protectors in laparoscopic colorectal
      procedures are cost effective and have SSI and retrieval-site tumor recurrence
      rates that compare favorably to published data.

PMID- 24105288
TI  - Application of minimally invasive video-assisted technique in papillary thyroid
      microcarcinoma.
AB  - BACKGROUND: Minimally invasive video-assisted technique (MIVAT) was initially
      described by Miccoli and colleagues in Italy. The MIVAT without gas infusion was
      introduced in the clinical practice to treat small benign thyroid nodules and had
      advantages in terms of cosmetic results compared with the conventional approach.
      OBJECT: To compare the outcome in papillary thyroid microcarcinoma (PTMC)
      patients treated with MIVAT and conventional procedure, and evaluate the
      feasibility of MIVAT applied in PTMC patients. MATERIALS AND METHODS: Data of 35
      PTMC patients with MIVAT and 33 others with conventional procedure were analyzed
      and compared, including postoperative outcomes, operative time, incidence of
      complications, the completeness of operation, and the prognosis of tumor after a
      follow-up of 5 years. RESULTS: With regard to the postoperative outcomes, a
      significantly statistical difference was found between MIVAT group and the
      conventional procedure group. The mean operative time in the MIVAT group was
      longer than that in the conventional group. However, it was similar to the
      convention group when only the mean operative time of the last 5 patients in the
      MIVAT group was estimated. The rate of temporary hypoparathyroidism was
      significantly lower in MIVAT group compared with the convention group, and the
      incidences of other complications had no significant difference. With regard to
      the completeness of operation and the prognosis of tumor, no differences were
      found between the 2 groups. CONCLUSIONS: MIVAT can be safely applied in PTMC
      patients with positive impact on patients outcome by comparable results to a
      conventional procedure after a median follow-up of 5 years. Thus it is a better
      alternative therapeutic treatment for patients with PTMC.

PMID- 24105289
TI  - Percutaneous cholecystostomy for treatment of acute cholecystitis in the era of
      early laparoscopic cholecystectomy.
AB  - BACKGROUND: Acute cholecystitis is a common surgical problem that is optimally
      managed by early laparoscopic cholecystectomy when possible. Percutaneous
      cholecystostomy (PC) has been used in certain high-risk cases as a bridge to
      surgery or for definitive therapy. The aim of this study was to determine the
      short-term and long-term outcomes of patients with acute cholecystitis treated by
      PC. STUDY DESIGN: Patients with acute cholecystitis treated by PC between 2005
      and 2011 in a tertiary hospital were identified from a prospectively maintained
      database. Outcome differences between patients with acalculous acute
      cholecystitis (AAC) and those with acute cholecystitis relating to gallstones
      were determined. RESULTS: There were 32 cases from a total of 443 patients with
      acute cholecystitis treated by PC during the study period. The overall 30-day
      mortality rate after PC was 9%. There were 8 patients with AAC in this series.
      Ischemic heart disease and chronic renal failure were noted in 47% and 41% of
      patients, respectively. In all cases, patients were considered unfit for surgery.
      AAC was more common in male patients. In all other aspects patients with AAC had
      similar characteristics to those with gallstones. Patients underwent percutaneous
      drainage a median of 3 days after admission with a direct transperitoneal route
      used in 16 (75%) cases. Positive bile cultures from the gallbladder were noted in
      60% of cases tested. Complications were noted in 53% of patients and were related
      to the cholecystostomy tube in 19% of cases. Subsequent cholecystectomy was
      performed in 9 (28%) patients, at a median of 73 days after initial tube
      insertion. No differences in morbidity and mortality were noted between patients
      with AAC and those with gallstones. The overall mean and 12 months survival was
      43 months and 72%, respectively. Hypotension at presentation (odds ratio 9.2; 95%
      confidence interval, 1.4-59.8; P=0.019) and absence of bile duct filling on
      cholecystography (odds ratio 4.6; 95% confidence interval, 1.2-16.3; P=0.017)
      were independently associated with decreased survival. CONCLUSIONS: PC can be
      performed safely in patients considered unfit for surgery at presentation.
      Outcomes are similar in patients with or without gallstones. Hypotension and
      absence of common bile duct filling on initial cholangiography are markers of
      decreased long-term survival. A significant number of patients require subsequent
      definitive cholecystectomy.

PMID- 24105290
TI  - Initial experience with robotic gasless transaxillary thyroidectomy for the
      management of graves disease: comparison of conventional open versus robotic
      thyroidectomy.
AB  - PURPOSE: The aim of this study was to report on our initial experiences with
      robotic gasless transaxillary thyroidectomy for the management of Graves disease
      (GD). METHODS: Among 257 patients with benign thyroid diseases who underwent
      thyroidectomy, 16 patients who underwent thyroidectomy for GD were analyzed from
      January 2009 to December 2010. These patients included 7 individuals who
      underwent robotic gasless transaxillary thyroidectomy (robot group; RG) and 9 who
      underwent conventional open thyroidectomy (open group; OG). Regardless of the
      type of surgery, all patients underwent subtotal thyroidectomy. The clinical
      characteristics and surgical outcomes of the 2 groups were compared. RESULTS:
      Patients in the RG were significantly younger at the time of surgery compared
      with those in the OG (P=0.028). The mean operative time was 171.29+/-18.88
      minutes for the RG and 89.44+/-7.08 minutes for the OG (P=0.001). The mean weight
      of the resected glands was 77.43+/-12.29 g for the RG and 85.56+/-20.37 g for the
      OG (P=0.896). The RG had a significantly shorter mean hospitalization period of
      3.0+/-0 days compared with 3.78+/-0.22 days of the OG. The mean number of times
      analgesics were used for pain control were 2.43+/-0.29 for the RG and 4.0+/-0.52
      for the OG (P=0.039). No cases in the RG were converted to open thyroidectomy.
      During a mean follow-up period of 14.43+/-1.49 months for the RG, no patients
      continued antithyroid drugs or developed recurrent GD. CONCLUSIONS: Robotic
      gasless transaxillary thyroidectomy is a technically feasible and safe procedure
      for the patients with GD that results in a scarless outcome on the neck. This
      procedure can be a promising alternative for endoscopic or conventional open
      thyroidectomy for the management of GD.

PMID- 24105291
TI  - Laparoscopic loop colostomy using an esophageal retractor and a penrose drain:
      surgical technique.
AB  - Laparoscopic Loop colostomy has been described in the literature as a safe and
      useful minimally invasive technique. It is indicated in patients with large
      perineal wounds requiring fecal diversion, obstructing lesions of the distal
      colon or rectum. The purpose of this article is to describe a modified version of
      this procedure which was used by 1 surgeon in our institution on a series of 5
      patients. In this method, an esophageal retractor and Penrose drain are used to
      tent up and exteriorize the desired segment of colon to be used for the colostomy
      site. Results were that all 5 were completed laparoscopically and there were no
      complications. In conclusion, this variation in the technique has been useful in
      our institution and others may find it worthwhile to consider. 

PMID- 24105292
TI  - Esophageal circumferential en bloc endoscopic submucosal dissection: assessment
      of a new technique.
AB  - BACKGROUND: Endoscopic esophageal piecemeal mucosectomy for high-grade dysplasia
      on Barrett's esophagus leads to suboptimal histologic evaluation, as well as
      recurrence on remaining mucosa. Circumferential en bloc mucosal resection would
      significantly improve the management of dysplastic Barrett's esophagus. Our aim
      was to describe a new method of esophageal circumferential endoscopic en bloc
      submucosal dissection (CESD) in a swine model. METHODS: After submucosal
      injection, circumferential incision was performed at each end of the esophageal
      segment to be removed. Mechanical submucosal dissection was performed from the
      proximal to the distal incision, using a mucosectomy cap over the endoscope. The
      removed mucosal ring was retrieved. Clinical, endoscopic, and histologic data
      were prospectively collected. RESULTS: Esophageal CESD was conducted on 5 pigs. A
      median mucosal length of 6.5 cm (range, 4 to 8 cm) was removed in the lower third
      of the esophagus. The mean duration of the procedure was 36 minutes (range, 17 to
      80 min). No procedure-related complication, including perforation, was observed.
      All animals exhibited a mild esophageal stricture at day 7, and a severe
      symptomatic stricture at day 14. Necropsy confirmed endoscopic findings with
      cicatricial fibrotic strictures. On histologic examination, an inflammatory cell
      infiltrate, diffuse fibrosis reaching the muscular layer, and incomplete
      reepithelialization were observed. CONCLUSIONS: CESD enables expeditious
      resection and thorough examination of large segments of esophageal mucosa in safe
      procedural conditions, but esophageal strictures occur in the majority of the
      cases. Efficient methods for stricture prevention are needed for this technique
      to be developed in humans.

PMID- 24105293
TI  - Hybrid endolaparoscopic management of biliary tract pathology in bariatric
      patients after gastric bypass: case report and review of a single-institution
      experience.
AB  - Obesity is the major risk factor in cholesterol crystal and gallstone formation.
      After an Roux-en-Y gastric bypass, biliary duct dilatation can appear and
      gallstone formation can cause biliary duct obstruction or gallstone pancreatitis.
      Management of this clinical situation can be challenging and many approaches have
      been reported. Endoscopic retrograde cholangiopancreatography plays an important
      role in the management of biliary duct obstruction in these patients. However, a
      previous modified anatomy makes this procedure technically difficult. For these
      reason, we describe our single-institution experience in the management of
      biliary duct obstruction utilizing a hybrid approach combining laparoscopy and
      flexible endoscopy. 

PMID- 24105294
TI  - Splenic infarction after N-butyl-2-cyanoacrylate injection for gastric varices:
      why does it happen?
AB  - Recent guidelines and consensus reports recommend endoscopic injection therapy
      with N-butyl-2-cyanoacrylate as the first-line treatment for bleeding-isolated
      gastric varices and gastroesophageal varices types 1 and 2. Embolization is a
      rare but serious complication of cyanoacrylate injection, which may be fatal in
      some cases. Herein, we present a patient who developed splenic infarction after N
      butyl-cyanoacrylate injection for gastroesophageal varices type 2 and discuss the
      potential reasons and tips to prevent the occurence of embolization. 

PMID- 24105295
TI  - Transumbilical single-incision laparoscopic hepatectomy using precoagulation and
      clipless technique in a patient with combined hepatocellular-cholangiocarcinoma:
      a case report.
AB  - We report our first case of single-incision laparoscopic hepatectomy in a 43-year
      old woman with a 30-mm solitary combined hepatocellular-cholangiocarcinoma. A
      port of single-incision laparoscopic surgery was inserted through the abdominal
      wall using a 2.5-cm single incision in the umbilical area. To obtain adequate
      operative view for the tumor in segment 6, a 5-mm flexible endoscope, roticulated
      instruments, and a miniloop retractor were used. After precoagulation with a 5-mm
      flexible microwave probe, liver resection was performed using laparoscopic
      ultrasonic shears, soft-coagulation devices, and a tissue-sealing knife.
      Subsequently, cholecystectomy was carried out for a gallbladder polyp. The
      procedure was successfully completed without conversion to conventional
      laparoscopic technique. The operation time was 180 minutes and operative blood
      loss was uncountable. Transumbilical single-incision laparoscopic hepatectomy
      using precoagulation and clipless techniques is feasible and seems to provide
      better cosmetic appearance in selected cases by qualified endoscopic liver
      surgeons. 

PMID- 24105296
TI  - Laparoscopic adrenalectomy for hemorrahagic adrenal pseudocyst discovered during
      pregnancy: report of a case.
AB  - Adrenal pseudocysts are rare cystic masses usually nonfunctional and
      asymptomatic, discovered incidentally during diagnostic imaging or when
      complicated by rupture and hemorrhage or infection. Few cases of hemorrhagic
      adrenal pseudocyst during pregnancy are reported, but a causal relationship
      between pregnancy and pseudocyst formation has not been shown. We describe a case
      of a 30-year-old pregnant woman referred to our surgical unit at the 20th week of
      gestation for incidental detection of left-side upper abdominal cystic mass, with
      signs of intralesion hemorrhage. The lesion was monitored and the woman gave
      birth at the 39th week, without complications. After 3 months from delivery, a
      multislide computed tomography scan confirmed a cystic mass measuring 10*7*10 cm.
      An elective transperitoneal laparoscopy was performed and a well-capsulated,
      hemorrhagic adrenal pseudocyst was removed. The optimal surgical treatment for
      hemorrhagic adrenal pseudocyst during pregnancy is still controversial. The
      present case shows that adrenal pseudocyst should be carefully monitored and can
      be treated by elective laparoscopic surgery after delivery. 

PMID- 24105297
TI  - Eosinophil depletion protects mice from tongue squamous cell carcinoma induced by
      4-nitroquinoline-1-oxide.
AB  - AIMS: Tumor-associated tissue eosinophilia (TATE) has been correlated with
      prognosis in oral squamous cell carcinoma (OSCC). This study aimed to investigate
      whether eosinophils depletion affects experimental oral carcinogenesis. METHODS
      AND RESULTS: BALB/c (wild type - WT) and eosinophil-deficient (Deltadb/GATA-1)
      mice were treated with the carcinogen 4-nitroquinoline-1-oxide (4NQO) in drinking
      water for 28 weeks. Tongues were collected for histopathological and
      immunohistochemical analysis, as well as for the evaluation of
      cytokines/chemokines by ELISA. The tongue SCC induced by 4NQO was associated with
      a rise in eosinophil numbers. WT-treated group showed a significantly increased
      incidence of SCC, with higher cytological atypia, in comparison with Deltadb/GATA
      1 mice. Consistently, the proliferative index was higher in WT compared to the
      Deltadb/GATA-1-treated group. No significant changes in the concentration of
      CCL3, CCL11 and TNF-alpha were detected for both groups after 4NQO treatment.
      CONCLUSIONS: These results suggest that eosinophils might be responsible for the
      deleterious outcome of experimental tongue carcinogenesis, given that their
      ablation protects mice from OSCC.

PMID- 24105298
TI  - PrP(Sc)-specific antibodies do not induce prion disease or misfolding of PrP(C)
      in highly susceptible Tga20 mice.
AB  - Transmissible spongiform encephalopathies (TSEs) are fatal neurodegenerative
      disorders caused by misfolding of a cellular protein PrP(C) into an infectious
      conformation PrP(Sc). Previously our group demonstrated induction of PrP(Sc)
      specific antibodies with a SN6b vaccine that targets regions of the protein that
      are exposed upon misfolding. There are concerns that these antibodies could
      function as templates to promote misfolding and cause disease. To evaluate the
      consequences of prolonged exposure to PrP(Sc)-specific antibodies in a prion
      sensitized animal, tga20 mice were vaccinated with the SN6b vaccine. No clinical
      signs of disease were detected up to 255 d post-vaccination, and postmortem assay
      of brains and spleens revealed no proteinase-K resistant PrP. These results
      suggest that vaccinating against TSEs with the SN6b antigen is safe from the
      standpoint of prion disease induction. 

PMID- 24105299
TI  - Clinical pharmacokinetics and pharmacodynamics of dapagliflozin, a selective
      inhibitor of sodium-glucose co-transporter type 2.
AB  - Sodium-glucose co-transporter 2 (SGLT2) is predominantly expressed in the S1
      segment of the proximal tubule of the kidney and is the major transporter
      responsible for mediating renal glucose reabsorption. Dapagliflozin is an orally
      active, highly selective SGLT2 inhibitor that improves glycemic control in
      patients with type 2 diabetes mellitus (T2DM) by reducing renal glucose
      reabsorption leading to urinary glucose excretion (glucuresis). Orally
      administered dapagliflozin is rapidly absorbed generally achieving peak plasma
      concentrations within 2 h. Dose-proportional systemic exposure to dapagliflozin
      has been observed over a wide dose range (0.1-500 mg) with an oral
      bioavailability of 78 %. Dapagliflozin has extensive extravascular distribution
      (mean volume of distribution of 118 L). Dapagliflozin metabolism occurs
      predominantly in the liver and kidneys by uridine diphosphate
      glucuronosyltransferase-1A9 to the major metabolite dapagliflozin 3-O-glucuronide
      (this metabolite is not an SGLT2 inhibitor at clinically relevant exposures).
      Dapagliflozin is not appreciably cleared by renal excretion (<2 % of dose is
      recovered in urine as parent). Dapagliflozin 3-O-glucuronide elimination occurs
      mainly via renal excretion, with 61 % of a dapagliflozin dose being recovered as
      this metabolite in urine. The half-life for orally administered dapagliflozin 10
      mg was 12.9 h. Maximal increases in urinary glucose excretion were seen at doses
      >=20 mg/day in patients with T2DM. No clinically relevant differences were
      observed in dapagliflozin exposure with respect to age, race, sex, body weight,
      food, or presence of T2DM. Pharmacodynamic changes are dependent on plasma
      glucose and renal function, and decreases in urinary glucose excretion were
      observed due to the lower filtered load (plasma glucose * glomerular filtration
      rate) in healthy volunteers compared to subjects with T2DM. After multiple doses
      of dapagliflozin, urinary glucose excretion was associated with dose-related
      decreases in plasma glucose parameters in subjects with T2DM. Patients with
      severe renal or hepatic impairment show higher systemic exposure to
      dapagliflozin. No clinically relevant drug interactions were observed that would
      necessitate dose adjustment of dapagliflozin when administered with other
      antidiabetic or cardiovascular medications, as well as drugs that could
      potentially influence dapagliflozin metabolism.

PMID- 24105300
TI  - First-principles study of the structural transformation, electronic structure,
      and optical properties of crystalline 2,6-diamino-3,5-dinitropyrazine-1-oxide
      under high pressure.
AB  - Periodic first-principles calculations have been performed to study the effect of
      high pressure on the geometric, electronic, and absorption properties of 2,6
      diamino-3,5-dinitropyrazine-1-oxide (LLM-105) under hydrostatic pressures of 0-50
      GPa. Obvious irregular changes in lattice constants, unit-cell angles, bond
      lengths, bond angles, and band gaps showed that crystalline LLM-105 undergoes
      four structural transformations at 8, 17, 25, and 42 GPa, respectively. The
      intramolecular H-bonds were strong at pressures of 0-41 GPa but weakened in the
      range 42-50 GPa. The lengths of the intermolecular H-bonds (<1.47 A) indicated
      that these H-bonds have covalent character and tend to induce the formation of a
      new twelve-membered ring. Analysis of the DOS showed that the interactions
      between electrons, especially the valence electrons, strengthen under the
      influence of pressure. The p states play a very important role in chemical
      reactions of LLM-105. The absorption spectrum of LLM-105 displayed more bands--as
      well as stronger bands--in the fundamental absorption region when the pressure
      was high rather than low. A new absorption peak due to O-H stretching appeared at
      18.3 eV above 40 GPa, indicating that covalent O-H bonds and a new twelve
      membered ring are present in LLM-105.

PMID- 24105301
TI  - Nitric oxide mediates Cd-dependent induction of signaling- associated genes.
AB  - The first reaction of plants to stress factors, including cadmium, is activation
      of signal transduction pathways leading to the mobilization of defense
      mechanisms. In a recent study we have demonstrated that cadmium causes a rapid
      induction of several genes associated with cellular signaling in soybean
      seedlings. Here we show that nitric oxide can be an important signaling molecule
      mediating observed increase in genes expression under short-term cadmium stress.

PMID- 24105302
TI  - Leaf water dynamics of Arabidopsis thaliana monitored in-vivo using terahertz
      time-domain spectroscopy.
AB  - The declining water availability for agriculture is becoming problematic for many
      countries. Therefore the study of plants under water restriction is acquiring
      extraordinary importance. Botanists currently follow the dehydration of plants
      comparing the fresh and dry weight of excised organs, or measuring their osmotic
      or water potentials; these are destructive methods inappropriate for in-vivo
      determination of plants' hydration dynamics. Water is opaque in the terahertz
      band, while dehydrated biological tissues are partially transparent. We used
      terahertz spectroscopy to study the water dynamics of Arabidopsis thaliana by
      comparing the dehydration kinetics of leaves from plants under well-irrigated and
      water deficit conditions. We also present measurements of the effect of dark
      light cycles and abscisic acid on its water dynamics. The measurements we present
      provide a new perspective on the water dynamics of plants under different
      external stimuli and confirm that terahertz can be an excellent non-contact probe
      of in-vivo tissue hydration. 

PMID- 24105304
TI  - Blood transfusion safety: patients at risk from human errors.

PMID- 24105305
TI  - Measuring the units: improving care of patients with alcohol-related liver
      disease.

PMID- 24105303
TI  - Induced hypothermia in severe bacterial meningitis: a randomized clinical trial.
AB  - IMPORTANCE: Despite advances in care, mortality and morbidity remain high in
      adults with acute bacterial meningitis, particularly when due to Streptococcus
      pneumoniae. Induced hypothermia is beneficial in other conditions with global
      cerebral hypoxia. OBJECTIVE: To test the hypothesis that induced hypothermia
      improves outcome in patients with severe bacterial meningitis. DESIGN, SETTING,
      AND PATIENTS: An open-label, multicenter, randomized clinical trial in 49
      intensive care units in France, February 2009-November 2011. In total, 130
      patients were assessed for eligibility and 98 comatose adults (Glasgow Coma Scale
      [GCS] score of <=8 for <12 hours) with community-acquired bacterial meningitis
      were randomized. INTERVENTIONS: Hypothermia group received a loading dose of 4
      degrees C cold saline and were cooled to 32 degrees C to 34 degrees C for 48
      hours. The rewarming phase was passive. Controls received standard care. MAIN
      OUTCOMES AND MEASURES: Primary outcome measure was the Glasgow Outcome Scale
      score at 3 months (a score of 5 [favorable outcome] vs a score of 1-4
      [unfavorable outcome]). All patients received appropriate antimicrobial therapy
      and vital support. Analyses were performed on an intention-to-treat basis. The
      data and safety monitoring board (DSMB) reviewed severe adverse events and
      mortality rate every 50 enrolled patients. RESULTS: After inclusion of 98
      comatose patients, the trial was stopped early at the request of the DSMB because
      of concerns over excess mortality in the hypothermia group (25 of 49 patients
      [51%]) vs the control group (15 of 49 patients [31%]; relative risk [RR], 1.99;
      95% CI, 1.05-3.77; P = .04). Pneumococcal meningitis was diagnosed in 77% of
      patients. Mean (SD) temperatures achieved 24 hours after randomization were 33.3
      degrees C (0.9 degrees C) and 37.0 degrees C (0.9 degrees C) in the hypothermia
      and control group, respectively. At 3 months, 86% in the hypothermia group
      compared with 74% of controls had an unfavorable outcome (RR, 2.17; 95% CI, 0.78
      6.01; P = .13). After adjustment for age, score on GCS at inclusion, and the
      presence of septic shock at inclusion, mortality remained higher, although not
      significantly, in the hypothermia group (hazard ratio, 1.76; 95% CI, 0.89-3.45; P
      = .10). Subgroup analysis on patients with pneumococcal meningitis showed similar
      results. Post hoc analysis showed a low probability to reach statistically
      significant difference in favor of hypothermia at the end of the 3 planned
      sequential analyses (probability to conclude in favor of futility, 0.977).
      CONCLUSIONS AND RELEVANCE: Moderate hypothermia did not improve outcome in
      patients with severe bacterial meningitis and may even be harmful. Careful
      evaluation of safety issues in future trials on hypothermia are needed and may
      have important implications in patients presenting with septic shock or stroke.
      TRIAL REGISTRATION: clinicaltrials.gov Identifier: NCT00774631.

PMID- 24105307
TI  - The role of neurosciences intensive care in trauma and neurosurgical conditions.
AB  - The creation of neurosciences intensive care units was born out of the awareness
      that a group of neurological and neurosurgical patients required specialized
      intensive medical and nursing care. This first of two articles describes the role
      of neurosciences intensive care in the management of trauma and neurosurgical
      conditions. 

PMID- 24105308
TI  - The role of neurosciences intensive care in neurological conditions.
AB  - The neurosciences intensive care unit provides specialized medical and nursing
      care to both the neurosurgical and neurological patient. This second of two
      articles describes the role it plays in the management of patients with
      neurological conditions. 

PMID- 24105309
TI  - Idiopathic normal pressure hydrocephalus: an important differential diagnosis.
AB  - Idiopathic normal pressure hydrocephalus, an uncommon but important differential
      diagnosis for ataxia, cognitive impairment and urinary incontinence, is
      surgically treatable, unlike many of its differential diagnoses. This article
      discusses its assessment, investigation and therapeutic interventions. 

PMID- 24105310
TI  - Computed tomography urography 1: techniques and technology.
AB  - Contrast-enhanced computed tomography urography has become possible because of
      the development of multidetector technology, which has evolved to try and
      increase its diagnostic efficacy and reduce the radiation exposure. This review
      highlights important aspects of computed tomography urography as an imaging
      technique. 

PMID- 24105311
TI  - Management of open fractures of the lower limb.
AB  - This article gives a practical guide for the management of open lower limb
      fractures. It outlines the referral criteria and pathway for definitive care in a
      specialist centre, the initial management steps that should be taken in the
      emergency department, and the principles of fixation, soft tissue coverage and
      antibiotic therapy. 

PMID- 24105312
TI  - The effect of medical school on postgraduate fitness to practise decisions: a
      retrospective cohort study.
AB  - Given evidence of differences between UK medical schools' curricula and
      assessments, and their graduates' performance in Royal college examinations, this
      retrospective cohort study analyses the effect of medical school on the incidence
      of General Medical Council fitness to practise sanctions. 

PMID- 24105313
TI  - Charles McBurney: pioneer in the diagnosis and treatment of appendicitis.

PMID- 24105315
TI  - Varicella and secondary pneumonia in a healthy child: is it time to introduce
      varicella vaccine in the UK?
AB  - A previously healthy 8-month-old boy presented to the emergency department with a
      1-week history of chickenpox infection. His routine immunizations were up-to
      date. His parents reported a high temperature (up to 39.5 degrees C) in the
      preceding 48 hours and that he also had a mild cough, episodes of vomiting and
      loose stools. He had fed poorly in the 24 hours before presentation. Clinical
      assessment revealed a temperature of 36.7 degrees C, heart rate 130/min,
      respiratory rate of 34/min and crusted chickenpox lesions. The infant was alert,
      smiling and playful, and systemic examination was otherwise unremarkable. He was
      admitted for monitoring of his fluid intake and temperature. As the infant
      continued to vomit intermittently in the 6 hours post admission, blood
      investigations were done and intravenous fluids were commenced. Laboratory
      investigations did not reveal biochemical evidence of dehydration, but they did
      show raised inflammatory markers: white blood cell count 24.8 * 109/litre,
      neutrophil count 19.8 * 109/litre and C-reactive protein 227mg/litre. In view of
      these results and the ongoing high fever, a chest X-ray was performed, revealing
      right upper lobe consolidation and collapse (Figure 1). Oral amoxicillin and
      flucloxacillin were started and oral feeding was successfully reestablished over
      the next 24 hours. He was discharged home after 48 hours, to complete a full 7
      day course of oral antibiotics. 

PMID- 24105314
TI  - The acute prescription of oxygen in orthopaedic trauma patients.
AB  - BACKGROUND: In trauma and orthopaedic surgery high flow oxygen can save lives by
      preventing severe hypoxaemia. Conversely, excessive oxygen can cause harm, and
      inadequate monitoring of its use has been reported in both pre-hospital and
      hospital audits. In 2008 the British Thoracic Society published guidelines on the
      use of emergency oxygen in adults. METHOD: Data were collected before, 3 months
      after and 12 months after the introduction of an oxygen prescription chart and
      education of junior doctors and ward staff. RESULTS: A total of 84 patients were
      recorded in the first study, 76 in the second and 72 in the third. After
      education and introduction of an oxygen prescription section on the drug charts
      the number of oxygen treatments correctly prescribed increased from 10/84 (12%)
      to 56/76 patients (74%, P<0.001) at 3 months. Twelve months after education and
      introduction of an oxygen prescription section on the drug charts the number of
      oxygen treatments prescribed decreased to 37/72 (51%, P<0.001). CONCLUSIONS:
      Education and the use of oxygen prescribing charts significantly improved the
      prescription of oxygen. The effect of the intervention fell at 12 months,
      suggesting poor sustainability. Continued education and feedback to ward staff is
      vital to maintain change and improve sustainability.

PMID- 24105316
TI  - Recurrent headaches: a case of neurological Behcet's disease.
AB  - A 48-year-old black male, of Nigerian heritage, presented with a 24-hour history
      of frontal headache of gradual onset. The headache characteristic was migranous,
      being described as throbbing in nature and located to the right frontal area with
      associated blurring of vision. Although similar to prior frequent headaches,
      there was now increasing unsteadiness on walking. Diagnosed 10 years earlier with
      Behcet's disease, the initial presentation was with oral and genital ulceration.
      Recurrent episodes of headache caused by neurological flare-ups resulted in a
      stroke at the age of 46 years. This previous stroke was ischaemic in character
      with involvement of the brainstem, pons, midbrain and right cerebral peduncle
      with extension into the right internal capsule. Surveillance brain imaging
      (computed tomographic and magnetic resonance imaging with venography) 10 months
      earlier showed brainstem disease activity (Figure 1a) with disease quiescence a
      month later (Figure 1b) following an escalation of immunosuppressant therapy.
      Regular medications comprised prednisolone 10 mg (however, regular recurrences
      had resulted in him taking doses of between 20 and 30 mg/day of prednisolone for
      most of the past 24 months) and azathioprine 150 mg daily, aspirin 75 mg daily,
      one adcal D3 twice daily with weekly alendronic acid, and omeprazole 20 mg daily.
      For headache he took topiramate 25 mg daily and for depression mirtazepine 15 mg
      daily. The patient was also addicted to a high level of cannabis use which he was
      reluctant to stop as he felt it helped his symptoms. On examination he was
      apyrexial and cardiovascularly stable. Neurological examination revealed a
      residual horizontal nystagmus to the right on lateral gaze, mild left hemiparesis
      with moderate spasticity, in addition to dysarthria and dysphonia from his prior
      stroke. A new feature was an exacerbation of gait unsteadiness. Blood tests were
      unremarkable and specifically the erythrocyte sedimentation rate was normal at 2
      mm/hr (normal range 0-10 mm/hr). Immediate therapy involved an increase in
      steroid dosage to methyl prednisolone 1 g/day for 3 days, followed by oral
      prednisolone 60 mg daily. This was maintained for 2 weeks and then reduced by 10
      mg/week to a maintenance dose of 10 mg/day. Magnetic resonance scanning revealed
      a marked increase in inflammation of the brainstem (Figure 1c). The patient
      required physiotherapy and occupational therapy with psychiatric input and was
      able to leave the hospital after 29 days. 

PMID- 24105317
TI  - Subclinical vasculitis in polymyalgia rheumatica.

PMID- 24105318
TI  - Keogh report: the focus on patients is essential.

PMID- 24105320
TI  - B-type natriuretic peptide for predicting morbidity and mortality after non
      cardiac surgery.

PMID- 24105321
TI  - Gene expression: RNA granules: the clock within.

PMID- 24105323
TI  - An unconventional case of scurvy.

PMID- 24105322
TI  - RNA in unexpected places: long non-coding RNA functions in diverse cellular
      contexts.
AB  - The increased application of transcriptome-wide profiling approaches has led to
      an explosion in the number of documented long non-coding RNAs (lncRNAs). While
      these new and enigmatic players in the complex transcriptional milieu are encoded
      by a significant proportion of the genome, their functions are mostly unknown.
      Early discoveries support a paradigm in which lncRNAs regulate transcription via
      chromatin modulation, but new functions are steadily emerging. Given the
      biochemical versatility of RNA, lncRNAs may be used for various tasks, including
      post-transcriptional regulation, organization of protein complexes, cell-cell
      signalling and allosteric regulation of proteins. 

PMID- 24105324
TI  - The impact of the lacto-ovo vegetarian diet on the erythrocyte superoxide
      dismutase activity: a study in the Romanian population.
AB  - BACKGROUND/OBJECTIVES: Recent studies have shown that vitamin B12 scavenges
      superoxide anion as effectively as superoxide dismutase (SOD), and has a key role
      in the defense against oxidative stress. The status of vitamin B12 is suboptimal
      in a substantial number of vegans and even vegetarians. We therefore evaluated in
      lacto-ovo vegetarians (LOVs) who did not take vitamin B12 supplements the impact
      of the duration of this diet on the vitamin B12 status, the erythrocyte SOD
      activity and the serum malondialdehyde (MDA) concentration. SUBJECTS/METHODS: The
      study group included 38 non-vegetarians and 48 LOVs divided, according to the
      duration of this diet, into two subgroups: LOV1 (2-10 years) and LOV2 (11-29
      years). The erythrocyte SOD activity and the serum concentrations of vitamin B12
      and MDA were assayed. RESULTS: In LOVs, the mean serum vitamin B12 concentration,
      the erythrocyte SOD activity and the mean serum MDA concentration were
      statistically significantly lower that in non-vegetarians. No significant
      association between the serum vitamin B12 and MDA concentrations and the duration
      of the LOV diet were observed. A significant inverse linear correlation between
      SOD activity and the duration of adherence to LOV diet was observed in LOVs.
      CONCLUSIONS: The duration of LOV diet has impact only on SOD activity. Further
      researches, both in vitro and in vivo, are necessary to understand the underlying
      molecular mechanism.

PMID- 24105325
TI  - Glycemic index claims on food labels: review of Health Canada's evaluation.
AB  - Recently Health Canada (HC) published its opinion that including glycemic index
      (GI) values on food labels would be misleading and not add value to nutrition
      labeling and dietary guidelines to help consumers make healthier food choices.
      Important areas of concern were identified by HC, but the discussion of them is
      scientifically invalid. HC concluded that GI has poor precision for labeling
      purposes based on incorrect application of the standard deviation. In fact, GI
      methodology is precise enough to distinguish, with high probability, low-GI (GI
      <= 55) from high-GI (GI >= 70) foods and to pass the Canadian Food Inspection
      Agency Nutrition Compliance Test procedure. HC rightly concluded that GI does not
      respond to portion size, whereas glycemic response does, but no valid evidence
      was provided to support the assertion that a lower-GI food could have a higher
      glycemic response. HC's focus on glycemic response could promote a low
      carbohydrate diet inconsistent with nutrition recommendations. HC correctly
      concluded that GI is unresponsive to the replacement of available- with
      unavailable-carbohydrate but this is irrelevant to GI labeling. HC is rightly
      concerned about promoting unhealthy low-GI foods; however, this could be avoided
      by prohibiting GI labeling on such foods. Therefore, HC has provided neither a
      helpful nor scientifically valid evaluation of GI for labeling purposes but has
      contributed to the wealth of misinformation about GI in the literature.
      Currently, Canadian consumers only have access to unregulated and misleading
      information about GI; well-crafted guidelines for GI labeling would provide
      consumers accurate information about GI and help them make healthier food
      choices.

PMID- 24105326
TI  - Frequency of KRAS mutations in adult Korean patients with acute myeloid leukemia.
AB  - Mutation of KRAS genes occurs with a frequency of 0.5-32 % in AML. In the present
      study, mutations of KRAS codon 12, 13, and 61 were detected by pyrosequencing and
      direct sequencing in AML. Seven KRAS mutations (7/123, 5.7 %) were detected. The
      most common mutation was a G-to-A transition in the second base of KRAS codon 13.
      No mutations were detected in KRAS codon 61. Combinations of KRAS and FLT3
      mutation were not found in the same patient. There was no statistically
      significant difference between patients with KRAS mutations and patients with
      wild-type KRAS in terms of sex, age, CBC at diagnosis, CD34 positivity, MPO
      positivity, FLT3 mutation, karyotype, progression-free survival, and overall
      survival, although this may be attributable to the small sample size. To our
      knowledge, this is the first report of the detection of KRAS mutation in Asian
      AML patients using pyrosequencing and direct sequencing. These two methods showed
      identical efficiencies in their ability to detect KRAS mutations in 84 patients.

PMID- 24105328
TI  - "Footprinting" her diagnosis: hypocalcaemia-induced muscle contraction.

PMID- 24105327
TI  - A research agenda on the management of intra-abdominal candidiasis: results from
      a consensus of multinational experts.
AB  - INTRODUCTION: intra-abdominal candidiasis (IAC) may include Candida involvement
      of peritoneum or intra-abdominal abscess and is burdened by high morbidity and
      mortality rates in surgical patients. Unfortunately, international guidelines do
      not specifically address this particular clinical setting due to heterogeneity of
      definitions and scant direct evidence. In order to cover this unmet clinical
      need, the Italian Society of Intensive Care and the International Society of
      Chemotherapy endorsed a project aimed at producing practice recommendations for
      the management of immune-competent adult patients with IAC. METHODS: A
      multidisciplinary expert panel of 22 members (surgeons, infectious disease and
      intensive care physicians) was convened and assisted by a methodologist between
      April 2012 and May 2013. Evidence supporting each statement was graded according
      to the European Society of Clinical Microbiology and Infection Diseases (ESCMID)
      grading system. RESULTS: Only a few of the numerous recommendations can be
      summarized in the Abstract. Direct microscopy examination for yeast detection
      from purulent and necrotic intra-abdominal specimens during surgery or by
      percutaneous aspiration is recommended in all patients with nonappendicular
      abdominal infections including secondary and tertiary peritonitis. Samples
      obtained from drainage tubes are not valuable except for evaluation of
      colonization. Prophylactic usage of fluconazole should be adopted in patients
      with recent abdominal surgery and recurrent gastrointestinal perforation or
      anastomotic leakage. Empirical antifungal treatment with echinocandins or lipid
      formulations of amphotericin B should be strongly considered in critically ill
      patients or those with previous exposure to azoles and suspected intra-abdominal
      infection with at least one specific risk factor for Candida infection. In
      patients with nonspecific risk factors, a positive mannan/antimannan or (1->3)
      beta-D-glucan (BDG) or polymerase chain reaction (PCR) test result should be
      present to start empirical therapy. Fluconazole can be adopted for the empirical
      and targeted therapy of non-critically ill patients without previous exposure to
      azoles unless they are known to be colonized with a Candida strain with reduced
      susceptibility to azoles. Treatment can be simplified by stepping down to an
      azole (fluconazole or voriconazole) after at least 5-7 days of treatment with
      echinocandins or lipid formulations of amphotericin B, if the species is
      susceptible and the patient has clinically improved. CONCLUSIONS: Specific
      recommendations were elaborated on IAC management based on the best direct and
      indirect evidence and on the expertise of a multinational panel.

PMID- 24105329
TI  - Nutrition support during extracorporeal membrane oxygenation (ECMO) in adults.

PMID- 24105330
TI  - Out-of-hospital cardiac arrest survival in Beirut, Lebanon.
AB  - BACKGROUND: Out-of-hospital cardiac arrest (OHCA) is used to evaluate the
      performance of the emergency medical service (EMS) system. Our study examined the
      characteristics and outcomes of OHCA cases presenting to a tertiary care center
      in Beirut, Lebanon. METHODS: A retrospective chart review of all adult OHCA
      patients admitted to the emergency department (ED) over a 3-year period was
      carried out. Data collection and analysis was performed using the Utstein
      guidelines. RESULTS: A total of 214 OHCA patients were presumed to have cardiac
      etiology; of them 205 (95.8%) underwent ED resuscitation. The mean age was 69+/
      15.4 years. More than half of the patients (54.2%) were witnessed, but
      unfortunately the bystander cardiopulmonary resuscitation rate was low (4.2%).
      Most of them were transported by EMS (71.5%). An automatic external defibrillator
      was rarely used (0.9%). Asystole was the predominant presenting rhythm in ED
      (81.8%). Eleven patients (5.5%) survived to hospital discharge and five (45.4%)
      had good neurological outcome. CONCLUSION: The OHCA survival rate in Beirut,
      Lebanon, is low. Bystander cardiopulmonary resuscitation and early defibrillation
      should be prioritized to achieve better outcomes.

PMID- 24105332
TI  - The healing of alkali-injured cornea is stimulated by a novel matrix regenerating
      agent (RGTA, CACICOL20): a biopolymer mimicking heparan sulfates reducing
      proteolytic, oxidative and nitrosative damage.
AB  - The efficacy of a chemically modified dextran - heparan sulfate mimicking
      regenerating agent (RGTA) on the healing of the rabbit cornea injured with alkali
      was examined. The eyes were injured with 0.15 N NaOH applied on the cornea or
      with 1.0 N NaOH using a 8 mm diameter filter paper disk. Then RGTA or placebo was
      applied on the cornea. In the last group of rabbits, corneas injured with the
      high alkali concentration were left without any treatment for four weeks;
      subsequently, the corneas were treated with RGTA or placebo. The central corneal
      thickness was measured using a pachymeter. The corneas were examined
      morphologically, immunohistochemically and for real time-PCR. Compared to control
      (unaffected) corneas, following the application of low alkali concentration the
      expression of urokinase-type plasminogen activator, metalloproteinase 9, nitric
      oxide synthase and xanthine oxidase was increased in the injured corneal
      epithelium of placebo-treated eyes, whereas the expression of antioxidant enzymes
      was reduced. Nitrotyrosine and malondialdehyde stainings appeared in the corneal
      epithelium. RGTA application suppressed the antioxidant/prooxidant imbalance and
      reduced the expression of the above-mentioned immunohistochemical markers. The
      corneal thickness increased after alkali injury, decreased during corneal healing
      after RGTA treatment faster than after placebo application. Following the injury
      with the high alkali concentration, corneal inflammation and neovascularization
      were highly pronounced in placebo-treated corneas, whereas in RGTA-treated
      corneas they were significantly supressed. When RGTA or placebo application was
      started later after alkali injury and corneas were ulcerated, subsequent RGTA
      treatment healed the majority of them. In conclusion, RGTA facilitates the
      healing of injured corneas via a reduction of proteolytic, oxidative and
      nitrosative damage.

PMID- 24105331
TI  - Surgical treatment of non-cystic fibrosis bronchiectasis in Brazilian children.
AB  - PURPOSE: To determine the clinical characteristics of patients submitted to
      surgical treatment for non-cystic fibrosis (CF) bronchiectasis, the indications
      for surgery, and the results obtained at a referral facility for pediatric
      thoracic surgery. METHODS: Between January 1998 and December 2009, we
      retrospectively reviewed the medical charts of 109 pediatric patients with non-CF
      bronchiectasis who underwent surgical treatment. These findings were subsequently
      analyzed by focusing on postoperative complications and long-term results.
      RESULTS: Of the 109 patients undergoing pulmonary resection, the mean age was 7.6
      years (ranging from 1 to 15.5 y-o) with male predominance (59 %). The most common
      procedure was segmentectomy (43 %) followed by left lower lobectomy (38 %). Minor
      postoperative complications occurred in 36 % of the patients; the most common was
      transient atelectasis (26 %), followed by air leak (6 %), and postoperative pain
      (4 %). There was one death within the 30-day postoperative period, but it was
      unrelated to the procedure. Eighty-three children were followed after discharge,
      with a mean follow-up period of 667 days. Sixty-five (76 %) patients showed
      improvement of clinical symptoms after surgery. CONCLUSIONS: Lung resection for
      the treatment of non-CF bronchiectasis in children is a safe procedure, with no
      life-treating morbidity and low mortality. This procedure also leads to
      significant improvements in symptoms and quality of life.

PMID- 24105333
TI  - Sustained life-like waveform capnography after human cadaveric tracheal
      intubation.
AB  - INTRODUCTION: Fresh frozen cadavers are effective training models for airway
      management. We hypothesised that residual carbon dioxide (CO2) in cadaveric lung
      would be detectable using standard clinical monitoring systems, facilitating
      detection of tracheal tube placement and further enhancing the fidelity of
      clinical simulation using a cadaveric model. METHODS: The tracheas of two fresh
      frozen unembalmed cadavers were intubated via direct laryngoscopy. Each tracheal
      tube was connected to a self-inflating bag and a sidestream CO2 detector. The
      capnograph display was observed and recorded in high-definition video. The
      cadavers were hand-ventilated with room air until the capnometer reached zero or
      the waveform approached baseline. RESULTS: A clear capnographic waveform was
      produced in both cadavers on the first postintubation expiration, simulating the
      appearances found in the clinical setting. In cadaver one, a consistent
      capnographic waveform was produced lasting over 100 s. Maximal end-tidal CO2 was
      8.5 kPa (65 mm Hg). In cadaver two, a consistent capnographic waveform was
      produced lasting over 50 s. Maximal end-tidal CO2 was 5.9 kPa (45 mm Hg).
      CONCLUSIONS: We believe this to be the first work to describe and quantify
      detectable end-tidal capnography in human cadavers. We have demonstrated that
      tracheal intubation of fresh frozen cadavers can be confirmed by life-like
      waveform capnography. This requires further validation in a larger sample size.

PMID- 24105335
TI  - The extended ppGalNAc-T family and their functional involvement in the metastatic
      cascade.
AB  - O-linked glycosylation of proteins begins with the attachment of a single N
      acetylgalactosamine (GalNAc) residue to a serine or threonine residue of the
      polypeptide and glycosylation of proteins can dramatically change their
      properties, interactions and activities. This initial attachment is catalysed by
      members of a family of 20 isoenzymes, the UDP-N-alpha-D-galactosamine:
      polypeptide N-acetylgalactosaminyltransferases or ppGalNAc-Ts. Why such a large
      family of isoenzymes are required to perform, apparently, a single function has
      been the subject of intense interest. The ppGalNAc-Ts, in fact, have overlapping,
      but distinct, substrate specificities and are differentially expressed in
      different cells and tissues and under different conditions of differentiation and
      development, allowing subtle and complex control of cellular glycosylation.
      Intriguingly, there is a growing body of evidence showing that altered expression
      of members of this transferase family are a common feature of many types of
      cancer and, crucially, that the resulting aberrant glycosylation has functional
      effects. Here, we review what is known of the expression and distribution of
      these intriguing transferases in health and in malignancy and, for the first
      time, bring together what is known of the functional and molecular effects of
      their disregulation in each step of the complex cascade of cancer metastasis.

PMID- 24105334
TI  - Rheumatoid arthritis in the elderly in the era of tight control.
AB  - The principles of treating rheumatoid arthritis (RA) have changed considerably in
      recent years. Disease-modifying treatment (if possible, methotrexate) should be
      started as soon as the diagnosis of RA is made. The purpose of treatment is to
      achieve remission or, alternatively, low disease activity, and patients should be
      assessed every 1-3 months if they have early RA in order to achieve this aim. The
      same principles of treatment should apply in the elderly. However, it is more
      difficult to assess RA activity in the elderly. Overall disease activity and/or
      pain may be overestimated, as elderly patients may suffer from other diseases.
      Conversely, the number of joints with synovitis can be underestimated compared
      with young patients, and regular ultrasound assessment should therefore be
      considered. Treatment may be more difficult because of concomitant diseases and
      the increase in drug-related side effects. The role of corticosteroids is still
      controversial as their short-term symptomatic effects on clinical activity and
      potential medium-term effect on structural deterioration are counter-balanced by
      their side effects. Dosages of methotrexate need to be adjusted for creatinine
      clearance. The anti-tumor necrosis factors (TNFs) appear to be slightly less
      effective in the elderly. The frequency of adverse effects of anti-TNFs is higher
      in an elderly population, although the same is seen with comparator disease
      modifying treatments. Limited information is available for rituximab and
      tocilizumab. Uncertainties remain about the management of RA in the elderly as
      there have been few studies in this population. The safety of the biotherapies
      therefore still needs to be confirmed, together with the benefit-risk balance of
      corticosteroid therapy compared with biological therapy.

PMID- 24105337
TI  - High serum 25-hydroxyvitamin D levels do not retard postmenopausal bone loss in
      Japanese women: the Yokogoshi study.
AB  - We conducted a cohort study exploring an association between serum 25
      hydroxyvitamin D (serum 25(OH)D) and parathyroid hormone (PTH) levels and 5-year
      changes in bone mineral density (BMD) in 482 postmenopausal women. High serum
      25(OH)D levels do not retard postmenopausal bone loss within the lumbar spine or
      femoral neck, and high PTH levels potentially increase hip bone loss. PURPOSE:
      The aim of this study was to explore an association between serum 25(OH)D levels
      and 5-year changes in BMD in postmenopausal women. METHODS: This 5-year cohort
      study included 482 women between 55 and 74 years of age who lived in a community
      in Japan. Medical examinations were conducted in 2005 and 2010. Data were
      obtained on baseline serum 25(OH)D and intact parathyroid hormone (iPTH) levels.
      Outcomes of this study were 5-year changes in BMDs of the lumbar spine and
      femoral neck. Covariates included years since menopause, body mass index (BMI),
      lifestyle factors, and weight change. Changes in BMDs among quartiles of serum
      25(OH)D were compared with analysis of covariance. RESULTS: The mean age of
      subjects was 63.1 years, and mean serum 25(OH)D levels were 56.0 nmol/L. Age and
      decrease in weight were significantly associated with decreases in BMDs of both
      the lumbar spine (P for trend < 0.001 and =0.002, respectively) and femoral neck
      (P for trend = 0.026 and <0.001, respectively); low BMI was associated with a
      decrease in lumbar spine BMD (P for trend < 0.001). No significant associations
      were found between serum 25(OH)D levels and changes in BMDs. High serum iPTH
      levels were associated with a greater decrease in femoral neck BMD (P for trend =
      0.026). CONCLUSIONS: High serum 25(OH)D levels do not retard postmenopausal bone
      loss within the lumbar spine or femoral neck, and high PTH levels potentially
      increase hip bone loss.

PMID- 24105336
TI  - Recombinant human prion protein inhibits prion propagation in vitro.
AB  - Prion diseases are associated with the conformational conversion of the cellular
      prion protein (PrP(C)) into the pathological scrapie isoform (PrP(Sc)) in the
      brain. Both the in vivo and in vitro conversion of PrP(C) into PrP(Sc) is
      significantly inhibited by differences in amino acid sequence between the two
      molecules. Using protein misfolding cyclic amplification (PMCA), we now report
      that the recombinant full-length human PrP (rHuPrP23-231) (that is unglycosylated
      and lacks the glycophosphatidylinositol anchor) is a strong inhibitor of human
      prion propagation. Furthermore, rHuPrP23-231 also inhibits mouse prion
      propagation in a scrapie-infected mouse cell line. Notably, it binds to PrP(Sc),
      but not PrP(C), suggesting that the inhibitory effect of recombinant PrP results
      from blocking the interaction of brain PrP(C) with PrP(Sc). Our findings suggest
      a new avenue for treating prion diseases, in which a patient's own unglycosylated
      and anchorless PrP is used to inhibit PrP(Sc) propagation without inducing immune
      response side effects. 

PMID- 24105338
TI  - Factors related to osteoporosis of postmenopausal women in Phayao, Thailand.
AB  - INTRODUCTION: This study was to investigate the associations between personal
      factors, health-related factors, history of fractures, and lifestyles and
      osteoporosis in the postmenopausal women. METHODS: This study was based on a
      retrospective case-control study design conducted in the Phayao Hospital, Phayao
      Province, Thailand. The 136 menopausal women aged 40 years and older were
      examined for bone density with dual x-ray absorptiometry. Those who had test
      results less than or equal to -2.5 standard deviation when compared to the
      maximum mean bone mineral density of young women (T score <= -2.5) were
      classified as the case group, and those who had test results more than -2.5
      standard deviation when compared to the maximum mean bone mineral density of
      young women (T score > -2.5) were classified as the control group. Data were
      collected using questionnaires. Binary logistic regression with forward stepwise
      (likelihood ratio) model selection was used to explore the associated factors.
      RESULTS: The factors statistically related to osteoporosis were body mass index
      (BMI; adjusted odds ratio (OR) = 0.81; 95 % confidence interval (CI), 0.71-0.93),
      age at menopause (OR = 0.88; 95 % CI, 0.79-0.99), history of fractures (OR =
      10.00; 95 % CI, 2.71-36.94), family history of osteoporosis (OR = 2.66; 95 % CI,
      1.04-6.77), and non-consumption of foods containing legumes, dried beans, and
      grains (OR = 13.84; 95 % CI, 2.08-92.11). CONCLUSIONS: It is recommended that
      more studies should be conducted on finding the optimal BMI and on the
      consumption of legumes, dried beans, and grains as osteoporotic protective
      factors.

PMID- 24105339
TI  - Concern and risk perception of osteoporosis and fracture among post-menopausal
      Australian women: results from the Global Longitudinal Study of Osteoporosis in
      Women (GLOW) cohort.
AB  - PURPOSE: The purpose of this study is to identify factors associated with concern
      and perception of risks of osteoporosis and osteoporotic fractures and determine
      whether bone mineral density (BMD) testing influenced concern and risk
      perception. METHODS: Study subjects (n = 1,082, age 55-94 years) were female
      Australian participants of the Global Longitudinal Study of Osteoporosis in Women
      (GLOW). Self-administered questionnaires were sent annually from 2007 to 2010.
      Study outcomes included 'concern about osteoporosis', 'perception of getting
      osteoporosis' and 'perception of fracture risk' compared to similar aged women.
      The closest post-BMD testing or baseline questionnaires were used for women with
      and without BMD testing, respectively. Multinomial logistic regression was used
      for the analysis. RESULTS: BMD testing, prior fracture after age 45, younger age
      and lower self-reported general health were significantly associated with being
      'very' or 'somewhat concerned' about osteoporosis and having a 'much higher' or
      'little higher' risk perception of osteoporosis and fractures. A poorer BMD
      result was associated with higher concern and higher risk perceptions. The
      presence of comorbidities, having >=2 falls in the preceding year and maternal
      osteoporosis were associated with higher concern. Maternal osteoporosis, presence
      of comorbidities, weight loss of >=5 kg in the preceding year and low body mass
      index were associated with higher perceptions of osteoporosis risk. CONCLUSION:
      Women's concern and risk perception of osteoporosis and osteoporotic fractures
      were reasonably well founded. However, increasing age, height loss, smoking and
      drinking were not associated with concern and perception despite being known
      osteoporosis risk factors. These factors should be considered in planning for
      education and awareness raising programmes.

PMID- 24105340
TI  - Short telomere lengths in peripheral blood leukocytes are associated with an
      increased risk of oral premalignant lesion and oral squamous cell carcinoma.
AB  - BACKGROUND: Oral premalignant lesions (OPLs) are precursors of oral squamous cell
      carcinoma (OSCC). Short telomeres in peripheral blood leukocytes (PBLs) are
      associated with increased risks of several cancers. However, it is unclear
      whether short leukocyte telomere length (LTL) predisposes individuals to OPL and
      OSCC. METHODS: LTL was measured in PBLs from 266 patients who had a diagnosis of
      either OPL (N = 174) or OSCC (N = 92) and from 394 age-matched and sex-matched
      controls. The association between LTL and the risk of OPL or OSCC, as well as the
      interaction of telomere length, cigarette smoking, and alcohol drinking on the
      risk of OPL or OSCC, were analyzed. RESULTS: The age-adjusted relative LTL was
      shortest in the OSCC group (1.64 +/- 0.29), intermediate in the OPL group (1.75
      +/- 0.43), and longest in the control group (1.82 +/- 0.36; Ptrend < .001). When
      the analysis was dichotomized at the median value in controls, adjusting for age,
      sex, smoking status, and alcohol drinking status, the odds ratio for the risk of
      OPL and OSCC associated with short LTL was 2.03 (95% confidence interval, 1.29
      3.21) and 3.47 (95% CI, 1.84-6.53), respectively, with significant dose-response
      effects for both associations. Among 174 patients with OPL, 23 progressed to
      OSCC, and the mean LTL was shorter in progressors than in nonprogressors (mean +/
      standard deviation: 1.66 +/- 0.35 vs 1.77 +/- 0.44, respectively), although the
      difference did not reach statistical significance (P = .258), probably because of
      the small number of progressors. An interaction analysis identified short LTL,
      smoking, and drinking alcohol as independent risk factors for OPL and OSCC.
      CONCLUSIONS: Short LTL was associated with increased risks of developing OPL and
      OSCC. The current results also indicated that short LTL likely predisposes
      patients to the malignant progression of OPL.

PMID- 24105341
TI  - Pain: A painful addiction.

PMID- 24105344
TI  - Glia: Reprogramming the residents.

PMID- 24105342
TI  - Molecular logic of neocortical projection neuron specification, development and
      diversity.
AB  - The sophisticated circuitry of the neocortex is assembled from a diverse
      repertoire of neuronal subtypes generated during development under precise
      molecular regulation. In recent years, several key controls over the
      specification and differentiation of neocortical projection neurons have been
      identified. This work provides substantial insight into the 'molecular logic'
      underlying cortical development and increasingly supports a model in which
      individual progenitor-stage and postmitotic regulators are embedded within highly
      interconnected networks that gate sequential developmental decisions. Here, we
      provide an integrative account of the molecular controls that direct the
      progressive development and delineation of subtype and area identity of
      neocortical projection neurons.

PMID- 24105345
TI  - The minimally invasive far medial subvastus approach for total knee arthroplasty
      in valgus knees.
AB  - PURPOSE: The lateral approach in the valgus knee asks for a lot of soft tissue
      releases during the arthrotomy. The hypothesis of this study was that the far
      medial subvastus approach could be used in valgus knees and would guarantee both
      functional and radiological good to excellent results. METHODS: This is a
      retrospective study on 78 patients (84 knees) undergoing primary total knee
      arthroplasty (TKA) for type I or II fixed valgus knees. The mean (SD)
      preoperative mechanical alignment was 187 degrees  (4 degrees ) HKA angle.
      Functional recovery, pain, tourniquet times, necessary soft tissue releases as
      well as radiological alignment were measured. RESULTS: The Knee Score improved
      significantly from 45 (10) to 90 (10) (P < 0.05) and the function score improved
      as well from 35 (20) to 85 (10) (P < 0.05). Flexion improved from 110 degrees 
      (10 degrees ) to 137 degrees  (8 degrees ). Hospital stay was 4 (1.2) days.
      Alignment was corrected to 181 degrees  (1.5 degrees ) HKA angle with a
      postoperative joint line shift of +2.8 (3.2) mm. No clinical instability, as
      evaluated by the senior author, or osteolytic lines was observed at minimal one
      year radiological follow-up. CONCLUSION: The far medial subvastus approach is an
      excellent approach to perform Krackow type I and II TKA with primary PS implants.

PMID- 24105343
TI  - The neurobiology of psychopathic traits in youths.
AB  - Conduct disorder is a childhood behaviour disorder that is characterized by
      persistent aggressive or antisocial behaviour that disrupts the child's
      environment and impairs his or her functioning. A proportion of children with
      conduct disorder have psychopathic traits. Psychopathic traits consist of a
      callous-unemotional component and an impulsive-antisocial component, which are
      associated with two core impairments. The first is a reduced empathic response to
      the distress of other individuals, which primarily reflects reduced amygdala
      responsiveness to distress cues; the second is deficits in decision making and in
      reinforcement learning, which reflects dysfunction in the ventromedial prefrontal
      cortex and striatum. Genetic and prenatal factors contribute to the abnormal
      development of these neural systems, and social-environmental variables that
      affect motivation influence the probability that antisocial behaviour will be
      subsequently displayed. 

PMID- 24105347
TI  - Influences of knee flexion angle and portal position on the location of femoral
      tunnel outlet in anterior cruciate ligament reconstruction with anteromedial
      portal technique.
AB  - PURPOSE: To evaluate the influences of knee flexion angle and portal position on
      the location of femoral tunnel outlet in anterior cruciate ligament (ACL)
      reconstruction with the anteromedial (AM) portal technique. METHODS: We recruited
      6 volunteers with 12 normal knees. Each knee was flexed 120 degrees  or 135
      degrees  and scanned with an open MRI. A 3D knee model was created. Virtual
      femoral tunnels were created on the footprint of the AM bundle and the
      posterolateral (PL) bundle of the ACL from three arthroscopic portals: the
      standard AM portal, the far medial and low portal, and the far medial and high
      (FMH) portal. The location of the femoral tunnel outlet was evaluated by
      comparing to the dissected cadaveric knee. RESULTS: Both increased flexion angle
      and lowering the drilling portal have a similar influence on the femoral tunnel
      outlet by moving them anterior and distally. Medialization of the portal moves
      them posteriorly and distally. PL tunnels created on the 120 degrees  knee model
      are more likely to be located under the lateral head of the gastrocnemius
      especially when they are drilled through the AM or FMH portals. CONCLUSION: If
      the femoral tunnel outlet is located under the soft tissue such as gastrocnemius
      attachment, suspension fixation devices may lapse into fixation failure by
      sitting on the soft tissue rather than the cortex bone surface. It is more
      desirable to drill in 135 degrees  knee flexion rather than 120 degrees , and
      through a lower portal, to avoid creating the femoral tunnel outlet under soft
      tissues.

PMID- 24105346
TI  - Comparison of 1.5- and 3-T MR imaging for evaluating the articular cartilage of
      the knee.
AB  - PURPOSE: The aim of this prospective study was to compare routine MRI scans of
      the knee at 1.5 and 3 T obtained in the same individuals in terms of their
      performance in the diagnosis of cartilage lesions. METHODS: One hundred patients
      underwent MRI of the knee at 1.5 and 3 T and subsequent knee arthroscopy. All MR
      examinations consisted of multiplanar 2D turbo spin-echo sequences. Three
      radiologists independently graded all articular surfaces of the knee joint seen
      at MRI. With arthroscopy as the reference standard, the sensitivity, specificity,
      and accuracy of 1.5- and 3-T MRI for detecting cartilage lesions and the
      proportion of correctly graded cartilage lesions within the knee joint were
      determined and compared using resampling statistics. RESULTS: For all readers and
      surfaces combined, the respective sensitivity, specificity, and accuracy for
      detecting all grades of cartilage lesions in the knee joint using MRI were 60,
      96, and 87% at 1.5 T and 69, 96, and 90% at 3 T. There was a statistically
      significant improvement in sensitivity (p < 0.05), but not specificity or
      accuracy (n.s.) for the detection of cartilage lesions at 3 T. There was also a
      statistically significant (p < 0.05) improvement in the proportion of correctly
      graded cartilage lesions at 3 T as compared to 1.5 T. CONCLUSION: A 3-T MR
      protocol significantly improves diagnostic performance for the purpose of
      detecting cartilage lesions within the knee joint, when compared with a similar
      protocol performed at 1.5 T. LEVEL OF EVIDENCE: III.

PMID- 24105349
TI  - Synthesis, characterization and reactivity of potassium and barium complexes
      containing phosphane-borane stabilized methanides.
AB  - The polymeric potassium complex [K{CH(PPh2BH3)2}]infinity (1) was prepared and
      used as a starting material for the syntheses of related N,N,N',N'
      tetramethylethylenediamine (tmeda) and N,N,N',N',N''
      pentamethyldiethylenetriamine (pmdta) ligated potassium derivatives
      [K{CH(PPh2BH3)2}(tmeda)2]infinity (2) and [K{CH(PPh2BH3)2}(pmdta)]2 (3). Salt
      metathesis reactions with [BaI2(thf)5] allowed the synthesis of the barium
      derivatives [BaI{CH(PPh2BH3)2}(thf)5] (5) and [Ba{CH(PPh2BH3)2}2(solv)2}] (solv =
      Et2O, thf) (6), which are more prone to subsequent reactions than the potassium
      derivatives. One of the resulting products,
      [Ba4O{CH(PPh2BH3)2}3{Ph2PCH(BH3)PPh2BH3}3] (7), which contains two different
      isomeric forms of the bis(borane) adduct of Ph2PCHPPh2, was isolated. The
      complexes were characterized by NMR techniques and single crystal X-ray
      diffraction measurements. 

PMID- 24105348
TI  - Femoral sizing in total knee arthroplasty is rotation dependant.
AB  - PURPOSE: The mismatch between the medio-lateral (ML) and the antero-posterior
      (AP) size of femoral components in total knee arthroplasty (TKA) has been linked
      to gender, ethnicity, morphotype and height differences in patients. The
      hypothesis of this study was that the AP size measurement of a femoral component
      increases with more external rotation in posterior referencing TKA. METHODS:
      During a 2-year period, 201 patients were included in this prospective study. The
      AP distance of the distal femur was measured with an AP sizer of the Vanguard
      (Biomet, Warsaw, US) knee system. This AP sizer allows to dial in external
      rotation by 1 degrees  increments and to determine the femoral size with an
      anterior boom. AP size was noted at 0 degrees , 3 degrees  and 5 degrees  of
      external rotation and then compared for ML matching. RESULTS: Antero-posterior
      and corresponding ML sizes match perfectly for the Vanguard at 0 degrees  of
      external rotation and a central boom position on the anterior femoral surface.
      Then, the anterior boom was positioned on the antero-lateral cortex and the AP
      size increased a mean (SD) 1 (0.5) mm. With 3 degrees  of external rotation, the
      AP size increased a mean (SD) 2.3 (0.4) mm and for 5 degrees  a mean (SD) 3.8
      (0.3) mm (P < 0.05). This increase in AP size resulted in ML overhang of 2.2
      (1.2) mm for 3 degrees  and 4.8 (2.6) mm for 5 degrees  (P < 0.05). CONCLUSIONS:
      Antero-posterior size measurement of the distal femur is determined by the
      anatomy of the anterior surface with a higher antero-lateral cortex and the
      amount of external rotation that is dialled in during surgery. Since these
      parameters vary case per case, the availability of narrow components offers more
      surgical options to the surgeon and its importance extends beyond the gender
      aspect allowing different amounts of external rotation to be used without ML
      overhang. LEVEL OF EVIDENCE: II.

PMID- 24105350
TI  - Modeling bicortical screws under a cantilever bending load.
AB  - Cyclic loading of surgical plating constructs can precipitate bone screw failure.
      As the frictional contact between the plate and the bone is lost, cantilever
      bending loads are transferred from the plate to the head of the screw, which over
      time causes fatigue fracture from cyclic bending. In this research, analytical
      models using beam mechanics theory were developed to describe the elastic
      deflection of a bicortical screw under a statically applied load. Four analytical
      models were developed to simulate the various restraint conditions applicable to
      bicortical support of the screw. In three of the models, the cortical bone near
      the tip of the screw was simulated by classical beam constraints (1) simply
      supported, (2) cantilever, and (3) split distributed load. In the final
      analytical model, the cortices were treated as an elastic foundation, whereby the
      response of the constraint was proportional to screw deflection. To test the
      predictive ability of the new analytical models, 3.5 mm cortical bone screws were
      tested in a synthetic bone substitute. A novel instrument was developed to
      measure the bending deflection of screws under radial loads (225 N, 445 N, and
      670 N) applied by a surrogate surgical plate at the head of the screw. Of the
      four cases considered, the analytical model utilizing an elastic foundation most
      accurately predicted deflection at the screw head, with an average difference of
      19% between the measured and predicted results. Determination of the bending
      moments from the elastic foundation model revealed that a maximum moment of 2.3 N
      m occurred near the middle of the cortical wall closest to the plate. The
      location of the maximum bending moment along the screw axis was consistent with
      the fracture location commonly observed in clinical practice. 

PMID- 24105351
TI  - Remote gaze tracking system on a large display.
AB  - We propose a new remote gaze tracking system as an intelligent TV interface. Our
      research is novel in the following three ways: first, because a user can sit at
      various positions in front of a large display, the capture volume of the gaze
      tracking system should be greater, so the proposed system includes two cameras
      which can be moved simultaneously by panning and tilting mechanisms, a wide view
      camera (WVC) for detecting eye position and an auto-focusing narrow view camera
      (NVC) for capturing enlarged eye images. Second, in order to remove the
      complicated calibration between the WVC and NVC and to enhance the capture speed
      of the NVC, these two cameras are combined in a parallel structure. Third, the
      auto-focusing of the NVC is achieved on the basis of both the user's facial width
      in the WVC image and a focus score calculated on the eye image of the NVC.
      Experimental results showed that the proposed system can be operated with a gaze
      tracking accuracy of +/-0.737 degrees ~+/-0.775 degrees  and a speed of 5~10
      frames/s. 

PMID- 24105353
TI  - Effect of tight flavin mononucleotide wrapping and its binding affinity on carbon
      nanotube covalent reactivities.
AB  - The controlled functionalization of single-walled carbon nanotubes (SWNTs) is a
      key to using them in high-end applications. We show that nanotube reactivity
      after covalent diazonium modification is governed by a chirality-specific
      surfactant binding affinity to SWNTs. Both metallic and semiconducting SWNTs
      tightly organized by a helical flavin mononucleotide (FMN) assembly exhibit two
      hundred times slower reactivity toward 4-methoxy benzenediazonium (4-MBD) than
      those wrapped by sodium dodecyl sulfate and this reactivity enables chirality-
      and metallicity-specific behaviours to be probed, as confirmed by absorption,
      Raman, and photoluminescence (PL) spectroscopy. Each reaction kinetic of the two
      step SWNT PL decays originating from electron transfer and the covalent reaction
      of 4-MBD, respectively, is inversely proportional to the binding affinity (Ka)
      between FMN and the SWNTs. The observed marginally higher reaction rate of the
      metallic nanotube compared to the semiconducting one results from the weaker Ka
      value of the metallic nanotubes with FMN. An enrichment demonstration of a few
      nanotube chiralities using selective and slow covalent diazonium chemistry
      demonstrates the importance of the binding affinity between the surfactant and
      the SWNTs. The study provides a handle on chirality-specific covalent chemistry
      via surfactant-SWNT binding affinity and impacts on future-sensing schemes. 

PMID- 24105352
TI  - Respiratory involvements among women exposed to the smoke of traditional biomass
      fuel and gas fuel in a district of Bangladesh.
AB  - OBJECTIVES: Burning of biomass fuel (cow-dung, crop residue, dried leaves, wood,
      etc.) in the kitchen releases smoke, which may impair the respiratory functions
      of women cooking there. This paper aimed to compare the respiratory symptoms
      between biomass fuel users and gas fuel users in Bangladesh. METHODS: A cross
      sectional survey was conducted through face-to-face interviews and chest
      examination of 224 adult women using biomass fuel in a rural village and 196
      adult women using gas fuel in an urban area. RESULTS: The prevalence of
      respiratory involvement (at least one among nine symptoms and two diseases) was
      significantly higher among biomass users than among gas users (29.9 vs. 11.2 %).
      After adjustment for potential confounders by a logistic model, the odds ratio
      (OR) of the biomass users for the respiratory involvement was significantly
      higher (OR = 3.23, 95 % confidence interval 1.30-8.01). The biomass fuel use
      elevated symptoms/diseases significantly; the adjusted OR was 3.04 for morning
      cough, 7.41 for nasal allergy, and 5.94 for chronic bronchitis. The mean peak
      expiratory flow rate of biomass users (253.83 l/min) was significantly lower than
      that of gas users (282.37 l/min). CONCLUSIONS: The study shows significant
      association between biomass fuel use and respiratory involvement among rural
      women in Bangladesh, although the potential confounding of urban/rural residency
      could not be ruled out in the analysis. The use of smoke-free stoves and adequate
      ventilation along with health education to the rural population to increase
      awareness about the health effects of indoor biomass fuel use might have roles to
      prevent these involvements.

PMID- 24105354
TI  - Seizures caused by ingestion of Atropa belladonna in a homeopathic medicine in a
      previously well infant: case report and review of the literature.
AB  - Atropa belladonna is a poisonous plant that can cause anticholinergic effects
      when ingested. Roots, leaves, and fruits of the plant contain the alkaloids
      atropine, hyoscyamine, and scopolamine, which can lead to an anticholinergic
      toxidrome; however, not all characteristics of the toxidrome are necessarily
      present in each case of poisoning. We present an infant who suffered serious
      seizures after ingestion of a homeopathic agent containing A. belladonna. The 20
      day-old infant arrived at the emergency department with fever and generalized
      seizures for 30 minutes, 2 hours after ingesting the correct dose of a
      homeopathic medication agent used for infantile colic. The patient was treated
      with intravenous benzodiazepines and antibiotics after a full sepsis work up; all
      the laboratory results were normal and the fever resolved after several hours.
      The infant recovered fully with normal neurological function and a normal
      electroencephalogram. This infant probably manifested what is known as the
      central anticholinergic syndrome. We discuss his presentation and review of the
      literature on this topic. 

PMID- 24105355
TI  - Thalidomide-induced hemorrhagic rash in a patient with myelofibrosis and delta
      granule storage pool disease.
AB  - Thalidomide is one of the immunomodulating agents used in current oncology
      practice. We present a case of hemorrhagic rash induced by thalidomide in a
      patient with delta granule storage pool disease. The patient was getting
      thalidomide for underlying myelofibrosis. 

PMID- 24105356
TI  - Integrative Reiki for cancer patients: a program evaluation.
AB  - OBJECTIVE: This mixed methods study sought to evaluate the outcomes of an
      integrative Reiki volunteer program in an academic medical oncology center
      setting. METHOD: We used de-identified program evaluation data to perform both
      quantitative and qualitative analyses of participants' experiences of Reiki
      sessions. The quantitative data were collected pre- and postsession using a
      modified version of the distress thermometer. The pre- and postsession data from
      the distress assessment were analyzed using a paired Student's : test. The
      qualitative data were derived from written responses to open-ended questions
      asked after each Reiki session and were analyzed for key words and recurring
      themes. RESULTS: Of the 213 pre-post surveys of first-time sessions in the
      evaluation period, we observed a more than 50% decrease in self-reported distress
      (from 3.80 to 1.55), anxiety (from 4.05 to 1.44), depression (from 2.54 to 1.10),
      pain (from 2.58 to 1.21), and fatigue (from 4.80 to 2.30) with P < .001 for all.
      Using conservative estimates that treat missing data as not endorsing Reiki, we
      found 176 (82.6%) of participants liked the Reiki session, 176 (82.6%) found the
      Reiki session helpful, 157 (73.7%) plan to continue using Reiki, and 175 (82.2%)
      would recommend Reiki to others. Qualitative analyses found that individuals
      reported that Reiki induced relaxation and enhanced spiritual well-being.
      CONCLUSIONS: An integrative Reiki volunteer program shows promise as a component
      of supportive care for cancer patients. More research is needed to evaluate and
      understand the impact that Reiki may have for patients, caregivers, and staff
      whose lives have been affected by cancer.

PMID- 24105357
TI  - A novel herbal formula induces cell cycle arrest and apoptosis in association
      with suppressing the PI3K/AKT pathway in human lung cancer A549 cells.
AB  - AIM OF THE STUDY: In recent years, the incidence of lung cancer, as well as the
      mortality rate from this disease, has increased. Moreover, because of acquired
      drug resistance and adverse side effects, the effectiveness of current
      therapeutics used for the treatment of lung cancer has decreased significantly.
      Chinese medicine has been shown to have significant antitumor effects and is
      increasingly being used for the treatment of cancer. However, as the mechanisms
      of action for many Chinese medicines are undefined, the application of Chinese
      medicine for the treatment of cancer is limited. The formula tested has been used
      clinically by the China National Traditional Chinese Medicine Master, Professor
      Zhonging Zhou for treatment of cancer. In this article, we examine the efficacy
      of Ke formula in the treatment of non-small cell lung cancer and elucidate its
      mechanism of action. METHODS: A Balb/c nude mouse xenograft model using A549
      cells was previously established. The mice were randomly divided into normal,
      mock, Ke, cisplatin (DDP), and co-formulated (Ke + DDP) groups. After 15 days of
      drug administration, the animals were sacrificed, body weight and tumor volume
      were recorded, and the tumor-inhibiting rate was calculated. A cancer pathway
      finder polymerase chain reaction array was used to monitor the expression of 88
      genes in tumor tissue samples. The potential antiproliferation mechanism was also
      investigated by Western blot analysis. RESULTS: Ke formula minimized chemotherapy
      related weight loss in tumor-bearing mice without exhibiting distinct toxicity.
      Ke formula also inhibited tumor growth, which was associated with the
      downregulation of genes in the PI3K/AKT, MAPK, and WNT/beta-catenin pathways. The
      results from Western blot analyses further indicated that Ke blocked the cell
      cycle progression at the G1/S phase and induced apoptosis mainly via the PI3K/AKT
      pathway. CONCLUSION: Ke formula inhibits tumor growth in an A549 xenograft mouse
      model with no obvious side effects. Moreover, Ke exhibits synergistic antitumor
      effects when combined with DDP. The mechanism of action of Ke is to induce cell
      cycle arrest and apoptosis by suppressing the PI3K/AKT pathway. Further research
      will be required to determine the mechanism of action behind the synergistic
      effect of Ke and DDP.

PMID- 24105358
TI  - A randomized placebo-controlled pilot study of the impact of healing touch on
      fatigue in breast cancer patients undergoing radiation therapy.
AB  - PURPOSE: This is a pilot study investigating the effect of healing touch (HT) on
      fatigue in breast cancer patients undergoing radiation therapy (RT).
      METHODS/DESIGN: This study presents the results of a within-subjects design
      randomized clinical trial where the treatment group was treated with HT, whereas
      the control group experienced sham therapy. The setting was a university RT
      clinic. The participants were breast cancer patients treated with lumpectomy or
      mastectomy, 21 to 75 years old with an Eastern Cooperative Oncology Group (ECOG)
      score of 0 to 2. The intervention was a 45-minute session of HT or sham therapy
      once a week during RT. Outcome measures included fatigue, quality of life (QOL),
      and anxiety/depression. RESULT: A total of 70 patients were approached, with 41
      completing the study. At completion, the HT participants tended to report higher
      levels of fatigue, statistically significant for interference ( : = .010) and
      usual fatigue ( : = .024). The control group tended to report greater reductions
      in fatigue relative to their own means than the HT group (Cohen's : = 0.30 to
      0.49 vs 0.06 to 0.18, respectively). There were no statistically significant
      differences between the groups for QOL. CONCLUSION: Our enrollment and retention
      indicate that HT is feasible for women during RT. Our pilot findings do not
      support a beneficial effect of HT on fatigue or QOL. Future research may explore
      increasing dose and teasing out therapist effect.

PMID- 24105359
TI  - A pilot study of a home-based motivational exercise program for African American
      breast cancer survivors: clinical and quality-of-life outcomes.
AB  - INTRODUCTION: African American breast cancer survivors engage in less physical
      activity compared with their Caucasian counterparts. There is a need for exercise
      intervention research that focuses on improving the overall health and long-term
      survivorship of African American breast cancer survivors, especially because they
      often have worse outcomes than Caucasian survivors. Study objectives were to
      determine whether African American participants increase physical activity and
      explore whether exercise had a positive impact on fitness and health. METHODS:
      African American breast cancer survivors, stage 0 to IIIA, within 2 years of
      completing primary cancer treatments were recruited for a 16-week home-based
      aerobic and resistance training exercise pilot study. Outcome measures assessed
      at baseline and postintervention included physical activity questionnaires and
      accelerometry, cardiopulmonary function (VO2peak) with gas exchange, muscle
      strength, Selective Functional Movement Assessment, and dual energy X-ray
      absorptiometry scans for body composition analysis. Assessments for fatigue and
      quality of life (QOL) were also completed at baseline and postintervention.
      Motivational interviewing was utilized to determine goals and explore exercise
      facilitators/barriers. Participants completed weekly exercise logs and received
      weekly phone calls. Wilcoxon signed rank tests were used to detect significant
      changes in physical activity and also changes in fitness/health parameters,
      fatigue, and QOL. Spearman correlation coefficients were used to examine
      relationships between physical activity and health measures. RESULTS: A total of
      17 women enrolled; 13 completed the intervention (76%). Mean age of the
      participants was 51 years. There was a significant increase in total minutes of
      weekly physical activity postintervention ( : = 271 minutes, S: = 151; : = .001).
      Significant improvements were found in cardiopulmonary fitness as measured by
      VO2peak with a mean increase of 2.03 mL/kg/min ( : = .01). Several strength
      measures significantly increased and also functional movement ( : = .005).
      Positive correlations existed between physical activity and several physical
      measures, with significant relationships between functional movement and some
      strength measures (eg, left arm extension: RS : = 0.61, : = .002). Total QOL and
      fatigue scores improved, but neither was significant. CONCLUSIONS: The
      intervention led to increased physical activity. As a result of increased levels
      of physical activity, improvements on several fitness/health parameters occurred.

PMID- 24105360
TI  - Effect of botanical immunomodulators on human CYP3A4 inhibition: implications for
      concurrent use as adjuvants in cancer therapy.
AB  - PURPOSE: Many botanical immunomodulators are used as adjuvants along with cancer
      chemotherapy. However, information on the impact of concurrent administration of
      such botanicals on pharmacokinetics of chemotherapy agents is inadequate. This
      study investigates inhibitory activities of 3 popular botanical adjuvants:
      ASPARAGUS RACEMOSU: (root aqueous extract; ARE), WITHANIA SOMNIFER: (root aqueous
      extract; WSE), and TINOSPORA CORDIFOLI: (stem aqueous extract, TCE) on human
      CYP3A4 isoenzyme, responsible for metabolism of several chemotherapy agents.
      EXPERIMENTAL DESIG: . Testosterone 6-beta hydroxylation was monitored using high
      performance liquid chromatography as an indicator of CYP3A4 catalytic activities.
      Ketoconazole (positive control) and extracts were studied at their in vivo
      relevant concentrations. RESULTS: TCE showed mild inhibition while no significant
      inhibitory activities were observed in WSE and ARE. TCE was further fractionated
      to obtain polar and nonpolar fractions. The nonpolar fraction showed significant
      CYP3A4 inhibition with IC50 13.06 +/- 1.38 ug/mL. Major constituents of nonpolar
      fraction were identified using HPLC-DAD-MS profiling as berberine, jatrorrhizine,
      and palmatine, which showed IC50 values as 6.25 +/- 0.30, 15.18 +/- 1.59, and
      15.53 +/- 1.89 ug/mL, respectively. CONCLUSION: Our findings suggest that
      constituents of TCE extract especially protoberberine alkaloids have the
      potential to interact with cancer chemotherapy agents that are metabolized by
      CYP3A4 in vivo.

PMID- 24105361
TI  - Psychosocial therapies for patients with cancer: a current review of
      interventions using psychoneuroimmunology-based outcome measures.
AB  - BACKGROUND: As part of a new standard of quality cancer care, the Institute of
      Medicine has recommended inclusion of therapies that address psychosocial needs
      of cancer patients. A range of psychosocial therapies for managing acute and
      chronic stress have been developed for patients with cancer, based on the
      scientific framework of psychoneuroimmunology (PNI). The current review aimed to
      identify studies of new and emerging PNI-based psychosocial therapies in patients
      with cancer that have used neuroendocrine-immune biomarkers as outcomes.
      Specifically, this review aimed to evaluate studies based on the cancer
      populations involved, types of psychosocial therapies, and PNI measures employed.
      METHOD: Methodology was guided by the Preferred Reporting Items for Systematic
      Reviews and Meta-Analyses (PRISMA) statement. The PubMed, EMBASE, PsychINFO,
      CINAHL, and Google Scholar online databases were searched using combinations of
      keywords obtained from previous reviews of psychosocial interventions. Studies
      from 2001 to 2012 were included if they ( : ) were published in English, ( : )
      used experimental or quasi-experimental designs, ( : ) evaluated psychosocial
      therapies, ( : ) involved cancer patients, and ( : ) reported results on at least
      one neuroendocrine or immune outcome measure. The search strategy identified 403
      records and 2 stages of screening were used to eliminate irrelevant studies.
      RESULT: A total of 24 cancer-specific studies of psychosocial therapies that used
      PNI-based outcome measures were included in this review. Most studies included
      early-stage breast cancer patients, and 2 major types of therapies emerged,
      cognitive-behavioral therapies and complementary medical therapies. Durations of
      interventions ranged widely, from 1.3 hours over a single week to 27 hours over
      18 weeks. Considerable diversity in PNI outcomes made statistical comparisons
      problematic. Studies of cognitive-behavioral therapies were found to have
      reported the most success in impacting PNI-based measures, which were typically
      functional measures of the immune system, for example, cytokines. CONCLUSION:
      Several issues related to research methodology are discussed. Most important,
      studies examining dose-response associations and resource allocation are needed
      to guide future research. A standardized panel of psychosocial instruments and
      biomarkers for PNI-based studies would enhance comparability of findings across
      studies when evaluating this body of research and assist with integrating
      psychosocial therapies into the standard of cancer care.

PMID- 24105362
TI  - Compliance with national nutrition recommendations among breast cancer survivors
      in "stepping stone".
AB  - INTRODUCTION: Compared with White breast cancer survivors, African American
      survivors are more likely to be overweight and obese. Differences in weight
      status may be attributed to differences in dietary intake; however, there is
      limited research pertaining to the dietary habits of African American breast
      cancer survivors. METHODS: We compared baseline dietary intakes of 31 overweight
      and obese African American breast cancer survivors enrolled in a healthy
      lifestyle intervention to national dietary guidelines and also examined beverage
      intake habits. Dietary intake was assessed using the National Cancer Institute's
      Diet History Questionnaire and beverage intake was assessed using 3-day food
      intake records. RESULTS: Overall, the majority of survivors consumed the
      recommended daily servings of fruits and vegetables (71.0%) and red meat (83.9%);
      however, survivors exceeded national recommendations for energy intake from fat
      (64.5%), saturated fat (87.1%), and added sugars (77.4%). Few women met the
      guidelines for whole grain and fiber intake (6.5% and 35.5%, respectively).
      Additionally, survivors consumed ~10% of total energy intake from beverages alone
      and drank only ~3.5 cups of water daily. CONCLUSIONS: Current dietary guidelines
      for cancer survivors recommend consuming >5 servings per day of fruits and
      vegetables and broad guidelines regarding limiting discretionary fat and added
      sugars but do not specify beverage intake recommendations. Future dietary
      interventions in African American breast cancer survivors should focus on
      reducing intake from dietary fat and added sugar, as well as increasing whole
      grain consumption as a means for increasing daily fiber intake. Furthermore,
      substituting caloric beverages with water or noncaloric beverages may be a
      strategy to decrease caloric intake in African American breast cancer survivors.
      Nutrition information targeting these nutrients could be administered during
      treatments or doctor's visits as a means to prevent weight gain that often occurs
      following diagnosis.

PMID- 24105364
TI  - Does gender matter? A one year follow-up of autistic, attention and anxiety
      symptoms in high-functioning children with autism spectrum disorder.
AB  - Gender differences in autism spectrum disorder (ASD) symptoms and associated
      problem behaviours over development may provide clues regarding why more males
      than females are diagnosed with ASD. Fifty-six high-functioning children with
      ASD, and 44 typically developing controls, half of the participants female, were
      assessed at baseline (aged 7-12 years) and one-year later, collecting measures of
      autism, attention and anxiety symptoms, school placement and support information.
      Findings indicated no gender differences in autistic symptoms. Males were more
      hyperactive and received more integration-aide support in mainstream schools, and
      females were more socially anxious. Overall, similar gender profiles were present
      across two time points. Lower hyperactivity levels in females might contribute to
      their under-identification. Implications are discussed using a biopsychosocial
      model of gender difference. 

PMID- 24105363
TI  - IgG4-related membranous nephropathy with high blood and low urine IgG4/IgG ratio:
      a case report and review of the literature.
AB  - Membranous nephropathy (MN) is a rare manifestation of IgG4-related disease.
      Interestingly, the significance of IgG4 has also been documented in idiopathic MN
      (IMN). Previous studies reported that urine IgG4/IgG ratios were significantly
      higher in IMN compared with other kinds of nephropathy, indicating that
      impairment of charge selectivity barrier seemed to be an obvious characteristic
      of IMN. Although high blood concentration of IgG4 is very common in IgG4-related
      MN, no study about the urine IgG4 has been described before. Here, we present a
      55-year-old male with IgG4-related MN. Complete remission of proteinuria was
      promptly achieved by glucocorticoid treatment without immunosuppressant.
      Consistent with previous reports, the serum antibody against M-type phospholipase
      A2 receptor was negative. Surprisingly, although the blood concentration of
      IgG4/IgG reached as high as 36 %, the urine concentration of IgG4/IgG was only 5
      %. The calculated ratio of the renal clearance of IgG4 to IgG of this patient
      (0.15) was obviously lower than that of five patients with IMN (0.53~0.81). We
      speculated that this phenomenon might be a clue of the different pathogenesis
      between IgG4-related MN and IMN. 

PMID- 24105365
TI  - Clinical features and treatment of ulcerative colitis-related severe
      gastroduodenitis and enteritis with massive bleeding after colectomy.
AB  - INTRODUCTION: Ulcerative colitis (UC) has been recognised as a systemic immune
      disorder that is not as restricted as colitis. UC-related gastrointestinal
      lesions with bleeding can develop soon after colectomy and can progress rapidly.
      Therefore, we considered the clinical features and treatment of these UC-related
      lesions. METHODS: We reviewed the patient data in our UC surgery database to
      evaluate its prevalence and features. RESULTS: We found 7/1,100 patients with UC
      related lesions between January 2000 and April 2013. These lesions developed at a
      mean of 24 (range 8-480) days after colectomy. Six of the seven patients suffered
      from gastrointestinal bleeding as an initial symptom that rapidly developed into
      massive bleeding or perforations. All of the patients were diagnosed with
      pancolitis; at the time of colectomy, fulminant, severe, moderate, and mild
      colitis were presented by four, one, one, and one patients, respectively. All
      patients with enteritis had consecutively developed other infectious
      complications, including anastomotic leakage, pyoderma gangrenosum, wound
      infection, and pneumonia. Although patients with bleeding did not respond to
      treatment with corticosteroids, they responded well to infliximab soon after its
      administration. Although six of the seven patients showed cytomegalo virus re
      activation in blood or pathological examinations, ganciclovir was not effective
      in its elimination. CONCLUSION: Although UC-related lesions with an unknown
      aetiology can occur after colectomy, immediate examination and treatment are
      required if gastrointestinal bleeding is found after surgery. Because
      gastrointestinal bleeding from UC-related lesions can worsen rapidly and may be
      related to mortality, early potent immunosuppressive therapy should be
      considered.

PMID- 24105366
TI  - Mutations in SH3PXD2B cause Borrone dermato-cardio-skeletal syndrome.
AB  - Borrone Dermato-Cardio-Skeletal (BDCS) syndrome is a severe progressive autosomal
      recessive disorder characterized by coarse facies, thick skin, acne conglobata,
      dysmorphic facies, vertebral abnormalities and mitral valve prolapse. We
      identified a consanguineous kindred with a child clinically diagnosed with BDCS.
      Linkage analysis of this family (BDCS1) identified five regions homozygous by
      descent with a maximum LOD score of 1.75. Linkage analysis of the family that
      originally defined BDCS (BDCS3) identified an overlapping linkage peak at
      chromosome 5q35.1. Sequence analysis identified two different homozygous
      mutations in BDCS1 and BDCS3, affecting the gene encoding the protein SH3 and PX
      domains 2B (SH3PXD2B), which localizes to 5q35.1. Western blot analysis of
      patient fibroblasts derived from affected individuals in both families
      demonstrated complete loss of SH3PXD2B. Homozygosity mapping and sequence
      analysis in a second published BDCS family (BDCS2) excluded SH3PXD2B. SH3PXD2B is
      required for the formation of functional podosomes, and loss-of-function
      mutations in SH3PXD2B have recently been shown to underlie 7 of 13 families with
      Frank-Ter Haar syndrome (FTHS). FTHS and BDCS share some overlapping clinical
      features; therefore, our results demonstrate that a proportion of BDCS and FTHS
      cases are allelic. Mutations in other gene(s) functioning in podosome formation
      and regulation are likely to underlie the SH3PXD2B-mutation-negative BDSC/FTHS
      patients. 

PMID- 24105368
TI  - Clinical utility gene card for: Xeroderma pigmentosum.

PMID- 24105367
TI  - Mate pair sequencing for the detection of chromosomal aberrations in patients
      with intellectual disability and congenital malformations.
AB  - Recently, microarrays have replaced karyotyping as a first tier test in patients
      with idiopathic intellectual disability and/or multiple congenital abnormalities
      (ID/MCA) in many laboratories. Although in about 14-18% of such patients, DNA
      copy-number variants (CNVs) with clinical significance can be detected,
      microarrays have the disadvantage of missing balanced rearrangements, as well as
      providing no information about the genomic architecture of structural variants
      (SVs) like duplications and complex rearrangements. Such information could
      possibly lead to a better interpretation of the clinical significance of the SV.
      In this study, the clinical use of mate pair next-generation sequencing was
      evaluated for the detection and further characterization of structural variants
      within the genomes of 50 ID/MCA patients. Thirty of these patients carried a
      chromosomal aberration that was previously detected by array CGH or karyotyping
      and suspected to be pathogenic. In the remaining 20 patients no causal SVs were
      found and only benign aberrations were detected by conventional techniques.
      Combined cluster and coverage analysis of the mate pair data allowed precise
      breakpoint detection and further refinement of previously identified balanced and
      (complex) unbalanced aberrations, pinpointing the causal gene for some patients.
      We conclude that mate pair sequencing is a powerful technology that can provide
      rapid and unequivocal characterization of unbalanced and balanced SVs in patient
      genomes and can be essential for the clinical interpretation of some SVs. 

PMID- 24105370
TI  - Clinical utility gene card for: 16p13.11 microdeletion syndrome.

PMID- 24105369
TI  - The CF-modifying gene EHF promotes p.Phe508del-CFTR residual function by altering
      protein glycosylation and trafficking in epithelial cells.
AB  - The three-base-pair deletion c.1521_1523delCTT (p.Phe508del, F508del) in the
      cystic fibrosis transmembrane conductance regulator (CFTR) is the most frequent
      disease-causing lesion in cystic fibrosis (CF). The CFTR gene encodes a chloride
      and bicarbonate channel at the apical membrane of epithelial cells. Altered ion
      transport of CFTR-expressing epithelia can be used to differentiate
      manifestations of the so-called CF basic defect. Recently, an 11p13 region has
      been described as a CF modifier by the North American CF Genetic Modifier Study
      Consortium. Selecting the epithelial-specific transcription factor EHF (ets
      homologous factor) as the likely candidate gene on 11p13, we have genotyped two
      intragenic microsatellites in EHF to replicate the 11p13 finding in the patient
      cohort of the European CF Twin and Sibling Study. We could observe an association
      of rare EHF haplotypes among homozygotes for c.1521_1523delCTT in CFTR, which
      exhibit a CF-untypical manifestation of the CF basic defect such as CFTR-mediated
      residual chloride secretion and low response to amiloride. We have reviewed
      transcriptome data obtained from intestinal epithelial samples of homozygotes for
      c.1521_1523delCTT in CFTR, which were stratified for their EHF genetic
      background. Transcripts that were upregulated among homozygotes for
      c.1521_1523delCTT in CFTR, who carry two rare EHF alleles, were enriched for
      genes that alter protein glycosylation and trafficking, both mechanisms being
      pivotal for the effective targeting of fully functional p.Phe508del-CFTR to the
      apical membrane of epithelial cells. We conclude that EHF modifies the CF
      phenotype by altering capabilities of the epithelial cell to correctly process
      the folding and trafficking of mutant p.Phe508del-CFTR. 

PMID- 24105371
TI  - Novel myosin mutations for hereditary hearing loss revealed by targeted genomic
      capture and massively parallel sequencing.
AB  - Hereditary hearing loss is genetically heterogeneous, with a large number of
      genes and mutations contributing to this sensory, often monogenic, disease. This
      number, as well as large size, precludes comprehensive genetic diagnosis of all
      known deafness genes. A combination of targeted genomic capture and massively
      parallel sequencing (MPS), also referred to as next-generation sequencing, was
      applied to determine the deafness-causing genes in hearing-impaired individuals
      from Israeli Jewish and Palestinian Arab families. Among the mutations detected,
      we identified nine novel mutations in the genes encoding myosin VI, myosin VIIA
      and myosin XVA, doubling the number of myosin mutations in the Middle East.
      Myosin VI mutations were identified in this population for the first time.
      Modeling of the mutations provided predicted mechanisms for the damage they
      inflict in the molecular motors, leading to impaired function and thus deafness.
      The myosin mutations span all regions of these molecular motors, leading to a
      wide range of hearing phenotypes, reinforcing the key role of this family of
      proteins in auditory function. This study demonstrates that multiple mutations
      responsible for hearing loss can be identified in a relatively straightforward
      manner by targeted-gene MPS technology and concludes that this is the optimal
      genetic diagnostic approach for identification of mutations responsible for
      hearing loss. 

PMID- 24105372
TI  - A novel in-frame deletion affecting the BAR domain of OPHN1 in a family with
      intellectual disability and hippocampal alterations.
AB  - Oligophrenin-1 (OPHN1) is one of at least seven genes located on chromosome X
      that take part in Rho GTPase-dependent signaling pathways involved in X-linked
      intellectual disability (XLID). Mutations in OPHN1 were primarily described as an
      exclusive cause of non-syndromic XLID, but the re-evaluation of the affected
      individuals using brain imaging displayed fronto-temporal atrophy and cerebellar
      hypoplasia as neuroanatomical marks. In this study, we describe clinical, genetic
      and neuroimaging data of a three generation Brazilian XLID family co-segregating
      a novel intragenic deletion in OPHN1. This deletion results in an in-frame loss
      of exon 7 at transcription level (c.781_891del; r.487_597del), which is predicted
      to abolish 37 amino acids from the highly conserved N-terminal BAR domain of
      OPHN1. cDNA expression analysis demonstrated that the mutant OPHN1 transcript is
      stable and no abnormal splicing was observed. Features shared by the affected
      males of this family include neonatal hypotonia, strabismus, prominent root of
      the nose, deep set eyes, hyperactivity and instability/intolerance to
      frustration. Cranial MRI scans showed large lateral ventricles, vermis hypoplasia
      and cystic dilatation of the cisterna magna in all affected males. Interestingly,
      hippocampal alterations that have not been reported in patients with loss-of
      function OPHN1 mutations were found in three affected individuals, suggesting an
      important function for the BAR domain in the hippocampus. This is the first
      description of an in-frame deletion within the BAR domain of OPHN1 and could
      provide new insights into the role of this domain in relation to brain and
      cognitive development or function. 

PMID- 24105373
TI  - Exome sequencing reveals HINT1 mutations as a cause of distal hereditary motor
      neuropathy.
AB  - Distal hereditary motor neuropathies (dHMNs) are a heterogenous group of genetic
      disorders with length-dependent degeneration of motor axons. Obtaining a genetic
      diagnosis in patients with dHMN remains challenging. We performed exome
      sequencing in a diagnostic setting in 12 patients with a clinical diagnosis of
      dHMN. Potential disease-causing variants in genes associated with dHMN and other
      forms of inherited neuropathies/motor neuron diseases were validated using
      Sequenom. The coverage in the genes studied was >95% with an average coverage of
      >50 times. In none of the patients a mutations was found in genes previously
      reported to be associated with dHMN. However, in 2/12 patients a recessive
      mutation in histidine triad nucleotide binding protein 1 (HINT1, recently
      discovered as a cause of axonal neuropathy with neuromyotonia) was identified.
      Our results demonstrate the diagnostic value of exome sequencing for patients
      with inherited neuropathies. The phenotypic spectrum of recessive mutations in
      HINT1 includes dHMN. HINT1 should be added to the list of genes to check for in
      dHMN. 

PMID- 24105374
TI  - Genetic genealogy reveals true Y haplogroup of House of Bourbon contradicting
      recent identification of the presumed remains of two French Kings.
AB  - Genetic analysis strongly increases the opportunity to identify skeletal remains
      or other biological samples from historical figures. However, validation of this
      identification is essential and should be done by DNA typing of living relatives.
      Based on the similarity of a limited set of Y-STRs, a blood sample and a head
      were recently identified as those belonging respectively to King Louis XVI and
      his paternal ancestor King Henry IV. Here, we collected DNA samples from three
      living males of the House of Bourbon to validate the since then controversial
      identification of these remains. The three living relatives revealed the
      Bourbon's Y-chromosomal variant on a high phylogenetic resolution for several
      members of the lineage between Henry IV and Louis XVI. This 'true' Bourbon's
      variant is different from the published Y-STR profiles of the blood as well as of
      the head. The earlier identifications of these samples can therefore not be
      validated. Moreover, matrilineal genealogical data revealed that the published
      mtDNA sequence of the head was also different from the one of a series of
      relatives. This therefore leads to the conclusion that the analyzed samples were
      not from the French kings. Our study once again demonstrated that in order to
      realize an accurate genetic identification of historical remains DNA typing of
      living persons, who are paternally or maternally related with the presumed donor
      of the samples, is required. 

PMID- 24105375
TI  - Clinical utility gene card for: Huntington's disease.

PMID- 24105377
TI  - Ensuring accuracy within the medicare physician fee schedule: an example from
      radiation oncology.

PMID- 24105378
TI  - WITHDRAWN: Hyaluronate for temporomandibular joint disorders.

PMID- 24105379
TI  - Bayesian estimation of the sensitivity and specificity of individual fecal
      culture and Paralisa to detect Mycobacterium avium subspecies paratuberculosis
      infection in young farmed deer.
AB  - A Bayesian latent class model was used to estimate the sensitivity and
      specificity of an immunoglobulin G1 serum enzyme-linked immunosorbent assay
      (Paralisa) and individual fecal culture to detect young deer infected with
      Mycobacterium avium subsp. paratuberculosis. Paired fecal and serum samples were
      collected, between July 2009 and April 2010, from 20 individual yearling (12-24
      month-old) deer in each of 20 South Island and 18 North Island herds in New
      Zealand and subjected to culture and Paralisa, respectively. Two fecal samples
      and 16 serum samples from 356 North Island deer, and 55 fecal and 37 serum
      samples from 401 South Island deer, were positive. The estimate of individual
      fecal culture sensitivity was 77% (95% credible interval [CI] = 61-92%) with
      specificity of 99% (95% CI = 98-99.7%). The Paralisa sensitivity estimate was 19%
      (95% CI = 10-30%), with specificity of 94% (95% CI = 93-96%). All estimates were
      robust to variation of priors and assumptions tested in a sensitivity analysis.
      The data informs the use of the tests in determining infection status at the
      individual and herd level.

PMID- 24105381
TI  - Determination of methomyl in the stomach contents of baited wildlife by gas
      chromatography-mass spectrometry.
AB  - The poisoning of wildlife with fly-bait containing the active ingredient methomyl
      is an intentional and illegal act in many jurisdictions. A case of 2 animals
      poisoned by methomyl through consumption of tainted bait at multiple stations is
      described. Although thermally and ultraviolet-labile, methomyl can be identified
      by gas chromatography-mass spectrometry and is detected in abundance in bait
      samples; however, it is not readily observed in tissues, owing to its rapid
      metabolism and elimination. The application of derivatizing functionalities, such
      as trimethylsilyl groups, stabilizes the methomyl-oxime metabolite to facilitate
      its detectability during exposure to the relatively harsh conditions of gas
      chromatography. This brief communication reports on the analytical detection of
      methomyl in baits and biological samples from poisoned wildlife. Essential to the
      case were the added determination of a fly-bait coactive ingredient, (Z)-9
      tricosene, and identification of a chemical indicator, caffeine, to confirm both
      the type of pesticide product involved in the poisoning incident and the vehicle
      used to perpetrate its delivery.

PMID- 24105380
TI  - Extra-adrenal retroperitoneal paraganglioma in a dog.
AB  - An extra-adrenal retroperitoneal paraganglioma was observed in a 10.5-year-old
      male Boxer dog. Additionally, the dog had an aortic base tumor, multiple thyroid
      adenomas, multiple testicular interstitial cell tumors, bilateral nodular adrenal
      cortical hyperplasia, and parathyroid gland hyperplasia. The hypothesis that the
      retroperitoneal mass represents a primary extra-adrenal paraganglioma rather than
      metastatic mass from the aortic body tumor is considered. Either primary or
      metastatic extra-adrenal retroperitoneal paragangliomas are rarely reported in
      dogs. 

PMID- 24105382
TI  - Lingual neurofibroma causing dysaesthesia of the tongue.
AB  - Neurofibroma is a benign tumour derived from the neural sheaths of peripheral
      nerves and composed of Schwann cells, fibroblast-like cells and intermediate
      cells. The usual clinical presentation of an oral neurofibroma is swelling. A 62
      year-old woman was referred to our department of otorhinolaryngology with
      irritation and dysaesthesia of the lateral aspect of the tongue. The only finding
      was a slightly red area from which a biopsy was taken. The macroscopic findings
      observed by the surgeon were consistent with normal tongue tissue. The
      histopathological examination showed a small, rounded tumour closely approximated
      to an invagination of the surface epithelium and with a small lymphatic
      infiltrate. The tumour was a neurofibroma. A Schwannoma type B was considered but
      the presence of small nerves and positive neurofilament reaction favoured a
      neurofibroma. The patient had no other neurofibromas or skin lesions. At a 3-week
      follow-up visit all symptoms had resolved. 

PMID- 24105383
TI  - Fatal measles pneumonitis during Hodgkin's lymphoma.
AB  - The treatment of measles pneumonitis in immunocompromised adults is not
      established. We describe a patient with Hodgkin's lymphoma who developed acute
      pneumonia during a measles infection. On day 13, intravenous ribavirin and
      immunoglobulins were administrated. On day 18, the patient developed acute
      respiratory failure. An examination of transbronchial pulmonary biopsies showed
      Warthin-Finkeldey giant cells that are pathognomonic of measles pneumonitis. The
      patient died despite aggressive supportive care. Our case and a review of
      literature show that measles pneumonitis is routinely fatal in patients with
      cancer. We suggest that antiviral drugs should be considered as soon as the
      diagnosis has been established. 

PMID- 24105384
TI  - Ureteral injury after posterior lumbar discectomy with interbody screw fixation.
AB  - We report a case of iatrogenic ureteral injury secondary to L5 laminectomy and
      microdiscectomy with L5-S1 bone graft with posterior lumbar interbodyfusion using
      presacral cancellous screw fixation, managed by initial ureteral stent placement
      and subsequent Boari bladder flap repair. A 33-year-old woman underwent L5
      laminectomy and microdiscectomy with L5-S1 bone graft with posterior lumbar
      interbody fusion using presacral cancellous screw fixation. On postoperative day
      10, she developed lower abdominal pain, vomiting and fever. Ultrasonogram and
      contrast-enhanced CT demonstrated a large pelvic urinoma secondary to a right
      lower ureteric injury. This was managed initially by ureteral stent placement and
      subsequent Boari bladder flap repair. Ureteral injury following spinal surgery is
      a rare surgical complication with significant morbidity and mortality. A high
      index of suspicion is essential for early appropriate management and renal
      salvage.

PMID- 24105385
TI  - Renal arteriovenous fistula revealed by severe hypertension during pregnancy.
AB  - A 35-year-old woman developed severe hypertension resistant to antihypertensive
      treatment during the second trimester of pregnancy at 24 weeks gestation. Doppler
      ultrasonography achieved the diagnosis of idiopathic renal arteriovenous fistula
      in the left kidney associated with parenchymal hypoperfusion. A Caesarean section
      was performed 6 days after the diagnosis because of severe pre-eclampsia. After
      delivery, the symptoms disappeared. Fistula persisted after follow-up for over 1
      year but with a dramatic decrease in its blood flow and normalisation of the left
      kidney hemodynamics. Nevertheless, embolisation was performed without
      complications to prevent recurrence during the next pregnancy expected by the
      patient. 

PMID- 24105386
TI  - Sternoclavicular joint septic arthritis: an interesting lesson in clinical
      anatomy.
AB  - An otherwise healthy 45-year-old man presented to our emergency department
      holding his left arm in abduction and external rotation. He reported pain in his
      left shoulder and chest for the preceding 10 days that had become much worse over
      the last 48 h and was eased only by holding his arm in this position. The CT of
      the chest revealed soft tissue swelling around the left sternoclavicular joint
      consistent with sternoclavicular joint septic arthritis with significant
      inflammatory involvement of the medial component of the left pectoralis major
      muscle. The patient was taken to theatre for washout of the left sternoclavicular
      joint and is currently recovering well at home on intravenous antibiotics. 

PMID- 24105387
TI  - Ultra-wide field imaging of retinopathy of prematurity (ROP) using Optomap-200TX.

PMID- 24105388
TI  - Bamboo spine and the lungs.

PMID- 24105389
TI  - Response of microchip solid-state laser to external frequency-shifted feedback
      and its applications.
AB  - The response of the microchip solid-state Nd:YAG laser, which is subjected to
      external frequency-shifted feedback, is experimentally and theoretically
      analysed. The continuous weak response of the laser to the phase and amplitude of
      the feedback light is achieved by controlling the feedback power level, and this
      system can be used to achieve contact-free measurement of displacement,
      vibration, liquid evaporation and thermal expansion with nanometre accuracy in
      common room conditions without precise environmental control. Furthermore, a
      strong response, including chaotic harmonic and parametric oscillation, is
      observed, and the spectrum of this response, as examined by a frequency
      stabilised Nd:YAG laser, indicates laser spectral linewidth broadening. 

PMID- 24105390
TI  - Reduced fat oxidation rates during submaximal exercise in adolescents with
      Crohn's disease.
AB  - BACKGROUND: Children with Crohn's disease (CD) suffer from malnutrition.
      Understanding substrate utilization during exercise may help patients with CD
      sustain a healthy active lifestyle without compromising nutrition. The aim of
      this study was to determine whether substrate utilization and bioavailability
      during exercise are altered in children with CD compared with controls. METHODS:
      Seven children with CD (mean age +/- SD: 15.2 +/- 2.3 yr) and 7 controls (14.4 +/
      2.3 yr) were matched by sex and biological age. Participants completed 60
      minutes of cycling at an intensity equivalent to 50% of their peak mechanical
      power. Rates of total fat and carbohydrate (CHO) oxidation, the amount of fat and
      CHO oxidized, and the contribution of fat and CHO to total energy expenditure
      were calculated from expired gases collected during exercise. Blood was collected
      before, during, and at the end of exercise and analyzed for insulin, free fatty
      acids, and glucose. RESULTS: Whole-body fat oxidation rate (expressed in mg . kg(
      1) of body weight per min) during exercise was lower in children with CD (5.8 +/-
      1.0) compared with controls (8.0 +/- 2.2, P < 0.05). Children with CD relied
      significantly more on CHO, with approximately 10% greater contribution toward
      total energy expenditure (P < 0.05) than controls. There were no differences in
      plasma insulin, free fatty acids, or glucose between the groups. CONCLUSIONS: Fat
      metabolism during exercise seems to be impaired in children with CD. A greater
      reliance on CHO is required to meet the energy demands of submaximal exercise.

PMID- 24105391
TI  - 6-Thioguanine levels in pediatric IBD patients: adherence is more important than
      dose.
AB  - BACKGROUND: Thiopurine immunosuppressants such as 6-mercaptopurine (6-MP) are
      widely used to maintain remission in children with both Crohn's disease and
      ulcerative colitis. Therapeutic efficacy is associated with higher red blood cell
      levels of the thiopurine metabolite 6-thioguanine (6-TGN). Studies in both
      children and adults have inexplicably failed to demonstrate a significant
      correlation between prescribed dose and level of 6-TGN. We aimed to quantify the
      relationship between 6-TGN levels and adherence. METHODS: We used electronic
      monitoring devices to assess adherence in children and adolescents with
      inflammatory bowel diseases who were prescribed 6-MP. RESULTS: During 3230 days
      of monitoring in 19 subjects, adherence to 6-MP was 74.2%. Due to the generally
      low adherence to the prescribed dose of 6-MP, the 6-TGN level was not correlated
      with the prescribed dose. The 6-TGN level was significantly correlated with the
      adherence-adjusted dose (R(2) = 0.395). It was also significantly correlated to
      adherence alone (R(2) = 0.478). Adherence to 5-aminosalicylic acid and 6-MP were
      significantly positively correlated (r(s)(9) = 0.82, P = 0.00), and a significant
      relationship was found between 5-aminosalicylic acid adherence and 6-TGN levels
      independent of 6-MP adherence. Furthermore, low adherence to 6-MP was associated
      with increased likelihood of escalation of medical therapy. CONCLUSIONS: Red
      blood cell 6-TGN levels are strongly correlated with the dose, when the dose is
      actually taken. Lack of efficacy of thiopurines may often be the result of poor
      adherence. Novel ways of assessing and improving adherence are necessary. Future
      trials should assess adherence in study participants. Intake of 5-aminosalicylic
      acid positively influences 6-TGN levels.

PMID- 24105392
TI  - Association of circulating vitamin D concentrations with intestinal but not
      systemic inflammation in inflammatory bowel disease.
AB  - BACKGROUND: Vitamin D may mediate immunomodulatory effects in patients with
      inflammatory bowel disease (IBD). The relationships between disease activity and
      circulating levels of total, free, and bioavailable 25(OH) vitamin D (25(OH)D)
      are poorly defined. The aim of this study was to measure circulating components
      of the vitamin D axis in patients with IBD and healthy controls and to correlate
      these with markers of disease activity, adjusting for potential confounders.
      METHODS: Clinical data were obtained and serum was analyzed for 25(OH)D and
      vitamin D-binding protein in patients with IBD and controls. Markers of systemic
      and intestinal (fecal calprotectin) inflammation were measured. RESULTS: Serum
      25(OH)D concentration was similar across 23 controls, 40 patients with Crohn's
      disease, and 31 with ulcerative colitis. An inverse correlation between 25(OH)D
      and calprotectin was noted in Crohn's disease (Pearson's r = -0.35, P = 0.040),
      ulcerative colitis (r = -0.39, P = 0.039), and all IBD together (r = -0.37, P =
      0.003), but not with systemic markers. A similar trend was noted for free and
      bioavailable 25(OH)D. This inverse correlation remained after partial correlation
      analysis correcting for sunlight exposure, total oral vitamin D intake, and
      obesity and was also noted among the subgroup without small intestinal
      involvement. CONCLUSIONS: Despite total, free, and bioavailable 25(OH)D
      concentrations being similar to those in a healthy control population, they
      inversely correlated strongly with intestinal inflammation. This was independent
      of potential malabsorption, sunlight exposure, and total vitamin D intake and
      obesity. Vitamin D may play an immunomodulatory role in IBD.

PMID- 24105394
TI  - Cutaneous manifestations in patients with inflammatory bowel diseases:
      pathophysiology, clinical features, and therapy.
AB  - The skin is one of the most common extraintestinal organ system affected in
      patients with inflammatory bowel disease (IBD), including both Crohn's disease
      and ulcerative colitis. The skin manifestations associated with IBD are
      polymorphic and can be classified into 4 categories according to their
      pathophysiology: (1) specific, (2) reactive, (3) associated, and (4) induced by
      IBD treatment. Cutaneous manifestations are regarded as specific if they share
      with IBD the same granulomatous histopathological pattern: perianal or metastatic
      Crohn's disease (commonly presenting with abscesses, fistulas or hidradenitis
      suppurativa-like features) is the prototype of this setting. Reactive cutaneous
      manifestations are different from IBD in the histopathology but have close
      physiopathological links: pyoderma gangrenosum, a neutrophil-mediated
      autoinflammatory skin disease typically manifesting as painful ulcers, is the
      paradigm of this group. Among the cutaneous diseases associated with IBD, the
      most commonly seen are erythema nodosum, a form of panniculitis most commonly
      involving bilateral pretibial areas, and psoriasis, a T helper 1/T helper 17
      mediated erythematous squamous inflammatory disease. Finally, the number of
      cutaneous adverse reactions because of IBD therapies is progressively increasing.
      The most frequent drug-induced cutaneous manifestations are psoriasis-like,
      eczema-like, and lichenoid eruptions, as well as cutaneous lupus erythematosus
      for biologics, and nonmelanoma skin cancer, mainly basal cell and squamous cell
      carcinomas for thiopurines.

PMID- 24105393
TI  - Comparative outcomes of younger and older hospitalized patients with inflammatory
      bowel disease treated with corticosteroids.
AB  - BACKGROUND: Data on the differences in inpatient treatment approaches and
      outcomes between younger and older patients with inflammatory bowel disease (IBD)
      are limited. Therefore, we used a parallel cohort study design to compare
      outcomes between younger and older patients with IBD. METHODS: All anti-tumor
      necrosis factor (TNF)-naive patients aged 60 years and older hospitalized at our
      institution between 2003 and 2011 and treated with corticosteroids for an IBD
      flare were matched 1:1 to younger patients aged 18 to 50 years. Rates of
      corticosteroid response, colectomy, and initiation of anti-TNF therapy were
      compared. RESULTS: Sixty-five patients were identified in each cohort. Median
      ages were 70 years (range, 60-94) and 30 years (range, 18-50) for the older and
      younger groups, respectively. Twenty-three percent of older patients were
      refractory to corticosteroids compared with 38% of the younger cohort (odds
      ratio, 0.5; 95% confidence intervals, 0.2-1.1). Older corticosteroid-refractory
      patients had surgery (80% versus 72%) and were started on anti-TNF therapy (20%
      versus 12%; P = 0.71), at a similar frequency as younger patients. Older steroid
      responsive patients were less likely to start an anti-TNF agent during the first
      year of follow-up than younger patients (7% versus 31%, P = 0.006), but there was
      no difference in 1-year colectomy rates (27% versus 28%, P = 0.63). CONCLUSIONS:
      Corticosteroid response was similar in older and younger patients hospitalized
      for IBD. Inpatient treatment for corticosteroid-refractory patients was similar
      between cohorts. Older corticosteroid-responsive patients were less likely to be
      treated with an anti-TNF than younger patients.

PMID- 24105395
TI  - Gut microbiota affects sensitivity to acute DSS-induced colitis independently of
      host genotype.
AB  - Caspase-deficient mice and wild-type (WT) mice show significant differences in
      their gut microbiota composition. These differences coincide with the observation
      that caspase-3-deficient mice carrying a natural caspase-11 mutation (Casp3/11(-/
      )) are less sensitive to acute dextran sodium sulfate-induced colitis than WT
      mice. For these reasons, we investigated the role of the microbiota in the
      development of colitis by cohousing WT and Casp3/11(-/-) mice. Microbial
      community fingerprinting by denaturing gradient gel electrophoresis analysis
      revealed that the similarities in gut microbial composition of WT and Casp3/11(-/
      ) mice increased after cohousing. In the acute dextran sodium sulfate-induced
      colitis model, Casp3/11(-/-) mice that were cohoused with WT mice showed
      increased weight loss and disease activity scores and increased neutrophil
      infiltration and inflammatory cytokine levels in their colon tissue compared with
      Casp3/11(-/-) mice that were not cohoused with WT mice. Also, we demonstrate that
      only the microbiota of the Casp3/11(-/-) mice cohoused with WT mice showed an
      important increase in Prevotella species. In conclusion, our cohousing
      experiments revealed that the colitogenic activity of the WT microbiota is
      transferable to Casp3/11(-/-) mice and that Prevotella species are likely to be
      involved. By contrast, the relative protection of Casp3/11(-/-) mice against
      dextran sodium sulfate damage is not transferred to WT mice after cohousing.
      These results underscore the need for in-depth studies of the bilateral
      interaction of host genes and microbiota to gain insight into the mechanisms of
      disease pathogenesis. Our findings also have important implications for the
      experimental design of disease studies in genetically modified mice and
      conclusions drawn from them.

PMID- 24105396
TI  - Some controversies in endovenous laser ablation of varicose veins addressed by
      optical-thermal mathematical modeling.
AB  - Minimally invasive treatment of varicose veins by endovenous laser ablation
      (EVLA) becomes more and more popular. However, despite significant research
      efforts performed during the last years, there is still a lack of agreement
      regarding EVLA mechanisms and therapeutic strategies. The aim of this article is
      to address some of these controversies by utilizing optical-thermal mathematical
      modeling. Our model combines Mordon's light absorption-based optical-thermal
      model with the thermal consequences of the thin carbonized blood layer on the
      laser fiber tip that is heated up to temperatures of around 1,000  degrees C due
      to the absorption of about 45% of the laser light. Computations were made in
      MATLAB. Laser wavelengths included were 810, 840, 940, 980, 1,064, 1,320, 1,470,
      and 1,950 nm. We addressed (a) the effect of direct light absorption by the vein
      wall on temperature behavior, comparing computations by using normal and zero
      wall absorption; (b) the prediction of the influence of wavelength on the
      temperature behavior; (c) the effect of the hot carbonized blood layer
      surrounding the fiber tip on temperature behavior, comparing wall temperatures
      from using a hot fiber tip and one kept at room temperature; (d) the effect of
      blood emptying the vein, simulated by reducing the inside vein diameter from 3
      down to 0.8 mm; (e) the contribution of absorbed light energy to the increase in
      total energy at the inner vein wall in the time period where the highest inner
      wall temperature was reached; (f) the effect of laser power and pullback velocity
      on wall temperature of a 2-mm inner diameter vein, at a power/velocity ratio of
      30 J/cm at 1,470 nm; (g) a comparison of model outcomes and clinical findings of
      EVLA procedures at 810 nm, 11 W, and 1.25 mm/s, and 1,470 nm, 6 W, and 1 mm/s,
      respectively. Interestingly, our model predicts that the dominating mechanism for
      heating up the vein wall is not direct absorption of the laser light by the vein
      wall but, rather, heat flow to the vein wall and its subsequent temperature
      increase from two independent heat sources. The first is the exceedingly hot
      carbonized layer covering the fiber tip; the second is the hot blood surrounding
      the fiber tip, heated up by direct absorption of the laser light. Both mechanisms
      are about equally effective for all laser wavelengths. Therefore, our model
      concurs the finding of Vuylsteke and Mordon (Ann Vasc Surg 26:424-433, 2012) of
      more circumferential vein wall injury in veins (nearly) devoid of blood, but it
      does not support their proposed explanation of direct light absorption by the
      vein wall. Furthermore, EVLA appears to be a more efficient therapy by the
      combination of higher laser power and faster pullback velocity than by the
      inverse combination. Our findings suggest that 1,470 nm achieves the highest EVLA
      efficacy compared to the shorter wavelengths at all vein diameters considered.
      However, 1,950 nm of EVLA is more efficacious than 1,470 nm albeit only at very
      small inner vein diameters (smaller than about 1 mm, i.e., veins quite devoid of
      blood). Our model confirms the efficacy of both clinical procedures at 810 and
      1,470 nm. In conclusion, our model simulations suggest that direct light
      absorption by the vein wall is relatively unimportant, despite being the supposed
      mechanism of action of EVLA that drove the introduction of new lasers with
      different wavelengths. Consequently, the presumed advantage of wavelengths
      targeting water rather than hemoglobin is flawed. Finally, the model predicts
      that EVLA therapy may be optimized by using 1,470 nm of laser light, emptying of
      the vein before treatment, and combining a higher laser power with a greater
      fiber tip pullback velocity.

PMID- 24105397
TI  - Optical-thermal mathematical model for endovenous laser ablation of varicose
      veins.
AB  - Endovenous laser ablation (EVLA) is successfully used to treat varicose veins.
      However, the exact working mechanism is still not fully identified and the
      clinical procedure is not yet standardized. Mathematical modeling of EVLA could
      strongly improve our understanding of the influence of the various EVLA
      processes. The aim of this study is to combine Mordon's optical-thermal model
      with the presence of a strongly absorbing carbonized blood layer on the fiber
      tip. The model anatomy includes a cylindrically symmetric blood vessel surrounded
      by an infinite homogenous perivenous tissue. The optical fiber is located in the
      center of the vessel and is withdrawn with a pullback velocity. The fiber tip
      includes a small layer of strongly absorbing material, representing the layer of
      carbonized blood, which absorbs 45% of the emitted laser power. Heat transfer due
      to boiling bubbles is taken into account by increasing the heat conduction
      coefficient by a factor of 200 for temperatures above 95  degrees C. The
      temperature distribution in the blood, vessel wall, and surrounding medium is
      calculated from a numerical solution of the bioheat equation. The simulations
      were performed in MATLABTM and validated with the aid of an analytical solution.
      The simulations showed, first, that laser wavelength did virtually not influence
      the simulated temperature profiles in blood and vessel wall, and, second, that
      temperatures of the carbonized blood layer varied slightly, from 952 to 1,104 
      degrees C. Our improved mathematical optical-thermal EVLA model confirmed
      previous predictions and experimental outcomes that laser wavelength is not an
      important EVLA parameter and that the fiber tip reaches exceedingly high
      temperatures.

PMID- 24105398
TI  - Effect of measurement on the ballistic-diffusive transition in turbid media.
AB  - The dependence of the transition between the ballistic and the diffusive regimes
      of turbid media on the experimental solid angle of the detection system is
      analyzed theoretically and experimentally. A simple model is developed which
      shows the significance of experimental conditions on the location of the
      ballistic-diffusive transition. It is demonstrated that decreasing the solid
      angle expands the ballistic regime; however, this benefit is bounded by the
      initial Gaussian beam diffraction. In addition, choosing the appropriate
      wavelength according to the model's principles provides another means of
      expanding the ballistic regime. Consequently, by optimizing the experimental
      conditions, it should be possible to extract the ballistic image of a tissue with
      a thickness of 1 cm.

PMID- 24105399
TI  - Measurements of erbium laser-ablation efficiency in hard dental tissues under
      different water cooling conditions.
AB  - Laser triangulation measurements of Er:YAG and Er,Cr:YSGG laser-ablated volumes
      in hard dental tissues are made, in order to verify the possible existence of a
      "hydrokinetic" effect that has been proposed as an alternative to the "subsurface
      water expansion" mechanism for hard-tissue laser ablation. No evidence of the
      hydrokinetic effect could be observed under a broad range of tested laser
      parameters and water cooling conditions. On the contrary, the application of
      water spray during laser exposure of hard dental material is observed to diminish
      the laser-ablation efficiency (AE) in comparison with laser exposure under the
      absence of water spray. Our findings are in agreement with the generally accepted
      principle of action for erbium laser ablation, which is based on fast subsurface
      expansion of laser-heated water trapped within the interstitial structure of hard
      dental tissues. Our measurements also show that the well-known phenomenon of
      ablation stalling, during a series of consecutive laser pulses, can primarily be
      attributed to the blocking of laser light by the loosely bound and recondensed
      desiccated minerals that collect on the tooth surface during and following laser
      ablation. In addition to the prevention of tooth bulk temperature buildup, a
      positive function of the water spray that is typically used with erbium dental
      lasers is to rehydrate these minerals, and thus sustaining the subsurface
      expansion ablation process. A negative side effect of using a continuous water
      spray is that the AE gets reduced due to the laser light being partially absorbed
      in the water-spray particles above the tooth and in the collected water pool on
      the tooth surface. Finally, no evidence of the influence of the water absorption
      shift on the hypothesized increase in the AE of the Er,Cr:YSGG wavelength is
      observed.

PMID- 24105400
TI  - Structure & bonding of the gold-subhalide cluster I-Au144Cl60[z].
AB  - The structure and bonding of the gold-subhalide compounds Au144Cl60([z]) are
      related to those of the ubiquitous thiolated gold clusters, or Faradaurates, by
      iso-electronic substitution of thiolate by chloride. Exact I-symmetry holds for
      the [z] = [2+,4+] charge-states, in accordance with new electrospray mass
      spectrometry measurements and the predicted electron shell filling. The high
      symmetry facilitates analysis of the global structure as well as the bonding
      network, with some striking results. 

PMID- 24105401
TI  - Saporin-S6: a useful tool in cancer therapy.
AB  - Thirty years ago, the type 1 ribosome-inactivating protein (RIP) saporin-S6 (also
      known as saporin) was isolated from Saponaria officinalis L. seeds. Since then,
      the properties and mechanisms of action of saporin-S6 have been well
      characterized, and it has been widely employed in the construction of conjugates
      and immunotoxins for different purposes. These immunotoxins have shown many
      interesting results when used in cancer therapy, particularly in hematological
      tumors. The high enzymatic activity, stability and resistance to conjugation
      procedures and blood proteases make saporin-S6 a very useful tool in cancer
      therapy. High efficacy has been reported in clinical trials with saporin-S6
      containing immunotoxins, at dosages that induced only mild and transient side
      effects, which were mainly fever, myalgias, hepatotoxicity, thrombocytopenia and
      vascular leak syndrome. Moreover, saporin-S6 triggers multiple cell death
      pathways, rendering impossible the selection of RIP-resistant mutants. In this
      review, some aspects of saporin-S6, such as the chemico-physical characteristics,
      the structural properties, its endocytosis, its intracellular routing and the
      pathogenetic mechanisms of the cell damage, are reported. In addition, the recent
      progress and developments of saporin-S6-containing immunotoxins in cancer
      immunotherapy are summarized, including in vitro and in vivo pre-clinical studies
      and clinical trials. 

PMID- 24105402
TI  - Small chemical chromatin effectors alter secondary metabolite production in
      Aspergillus clavatus.
AB  - The filamentous fungus Aspergillus clavatus is known to produce a variety of
      secondary metabolites (SM) such as patulin, pseurotin A, and cytochalasin E. In
      fungi, the production of most SM is strongly influenced by environmental factors
      and nutrients. Furthermore, it has been shown that the regulation of SM gene
      clusters is largely based on modulation of a chromatin structure. Communication
      between fungi and bacteria also triggers chromatin-based induction of silent SM
      gene clusters. Consequently, chemical chromatin effectors known to inhibit
      histone deacetylases (HDACs) and DNA-methyltransferases (DNMTs) influence the SM
      profile of several fungi. In this study, we tested the effect of five different
      chemicals, which are known to affect chromatin structure, on SM production in A.
      clavatus using two growth media with a different organic nitrogen source. We
      found that production of patulin was completely inhibited and cytochalasin E
      levels strongly reduced, whereas growing A. clavatus in media containing soya
      derived peptone led to substantially higher pseurotin A levels. The HDAC
      inhibitors valproic acid, trichostatin A and butyrate, as well as the DNMT
      inhibitor 5-azacytidine (AZA) and N-acetyl-D-glucosamine, which was used as a
      proxy for bacterial fungal co-cultivation, had profound influence on SM
      accumulation and transcription of the corresponding biosynthetic genes. However,
      the repressing effect of the soya-based nitrogen source on patulin production
      could not be bypassed by any of the small chemical chromatin effectors.
      Interestingly, AZA influenced some SM cluster genes and SM production although no
      Aspergillus species has yet been shown to carry detectable DNA methylation. 

PMID- 24105403
TI  - Impact of risk assessments on prophylactic antiemetic prescription and the
      incidence of postoperative nausea and vomiting: a cluster-randomized trial.
AB  - BACKGROUND: Clinical prediction models have been shown to have moderate
      sensitivity and specificity, yet their use will depend on implementation in
      clinical practice. The authors hypothesized that implementation of a prediction
      model for postoperative nausea and vomiting (PONV) would lower the PONV incidence
      by stimulating anesthesiologists to administer more "risk-tailored" prophylaxis
      to patients. METHODS: A single-center, cluster-randomized trial was performed in
      12,032 elective surgical patients receiving anesthesia from 79 anesthesiologists.
      Anesthesiologists were randomized to either exposure or nonexposure to automated
      risk calculations for PONV (without patient-specific recommendations on
      prophylactic antiemetics). Anesthesiologists who treated less than 50 enrolled
      patients were excluded during the analysis to avoid too small clusters, yielding
      11,613 patients and 57 anesthesiologists (intervention group: 5,471 and 31; care
      as-usual group: 6,142 and 26). The 24-h incidence of PONV (primary outcome) and
      the number of prophylactic antiemetics administered per patient were studied for
      risk-dependent differences between allocation groups. RESULTS: There were no
      differences in PONV incidence between allocation groups (crude incidence
      intervention group 41%, care-as-usual group 43%; odds ratio, 0.97; 95% CI, 0.87
      1.1; risk-dependent odds ratio, 0.92; 95% CI, 0.80-1.1). Nevertheless,
      intervention-group anesthesiologists administered more prophylactic antiemetics
      (rate ratio, 2.0; 95% CI, 1.6-2.4) and more risk-tailored than care-as-usual
      group anesthesiologists (risk-dependent rate ratio, 1.6; 95% CI, 1.3-2.0).
      CONCLUSIONS: Implementation of a PONV prediction model did not reduce the PONV
      incidence despite increased antiemetic prescription in high-risk patients by
      anesthesiologists. Before implementing prediction models into clinical practice,
      implementation studies that include patient outcomes as an endpoint are needed.

PMID- 24105404
TI  - Diaphragmatic function is preserved during severe hemorrhagic shock in the rat.
AB  - BACKGROUND: Acute diaphragmatic dysfunction has been reported in septic and
      cardiogenic shock, but few data are available concerning the effect of
      hemorrhagic shock on diaphragmatic function. The authors examined the impact of a
      hemorrhagic shock on the diaphragm. METHODS: Four parallel groups of adult rats
      were submitted to hemorrhagic shock induced by controlled exsanguination
      targeting a mean arterial blood pressure of 30 mmHg for 1 h, followed by a 1-h
      fluid resuscitation with either saline or shed blood targeting a mean arterial
      blood pressure of 80 mmHg. Diaphragm and soleus strip contractility was measured
      in vitro. Blood flow in the muscle microcirculation was measured in vivo using a
      Laser Doppler technique. Muscle proinflammatory cytokine concentrations were also
      measured. RESULTS: Hemorrhagic shock was characterized by a decrease in mean
      arterial blood pressure to 34 +/- 5 mmHg (-77 +/- 4%; P< 0.05) and high plasma
      lactate levels (7.6 +/- 0.9 mM; P < 0.05). Although tetanic tension of the
      diaphragm was not altered, hemorrhagic shock induced dramatic impairment of
      tetanic tension of the soleus (-40 +/- 19%; P < 0.01), whereas proinflammatory
      cytokine levels were low and not different between the two muscles. Resuscitation
      with either blood or saline did not further modify either diaphragm or soleus
      performance and proinflammatory cytokine levels. The shock-induced decrease in
      blood flow was much more pronounced in the soleus than in the diaphragm (-75 +/-
      13% vs. -17 +/- 10%; P = 0.02), and a significant interaction was observed
      between shock and muscle (P < 0.001). CONCLUSION: Diaphragm performance is
      preserved during hemorrhagic shock, whereas soleus performance is impaired, with
      no further impact of either blood or saline fluid resuscitation.

PMID- 24105407
TI  - Discovery of polymorphism-dependent emission for crystalline boron-dipyrromethene
      dye.
AB  - 4-Methoxycarbonylphenyl-substituted BODIPY (boron-dipyrromethene) dye gives, in
      the solid state, three polymorphs. In spite of the absence of any strong
      intermolecular interactions in all crystalline forms, the three polymorphs show
      different photoluminescence properties. This behavior highlights the importance
      of molecular arrangements of the BODIPY moieties in the crystalline state in
      perturbing their photophysical properties. 

PMID- 24105406
TI  - Long-term results of a prospective comparison of Roux-en-Y gastric bypass versus
      a variant of biliopancreatic diversion in a non-superobese population (BMI 35-50
      kg/m(2)).
AB  - BACKGROUND: This study presents late results of a previously published 2-year
      prospective comparison between Roux-en-Y gastric bypass (RYGBP) versus
      biliopancreatic diversion with Roux-en-Y gastric bypass (BPD-RYGBP) in an
      exclusively non-superobese population. METHODS: From a cohort of 130 patients
      with a BMI of 35-50 kg/m(2), 65 were randomly selected to undergo RYGBP and 65 to
      BPD-RYGBP. All underwent follow-up evaluation at 1, 3, 6, and 12 months
      postoperatively and every year thereafter. RESULTS: Follow-up at the eighth year
      was achieved in 60% of the BPD-RYGBP and in 58% of the RYGBP group (p = 1.00).
      Mean excess weight loss (EWL%), was significantly higher following BPD-RYGBP
      (76.89 +/- 1.53) as compared to RYGBP (67.17 +/- 1.43) (p = 0.0004). The mean
      success rate (percentage of patients with EWL% >=50%) was significantly higher
      after BPD-RYGBP (95.85 +/- 1.01) than RYGBP (75.91 +/- 3.58) (p = 0.0001). No
      significant differences were observed for late non-metabolic complications. The
      incidence of anemia, iron deficiency, B12 deficiency, and low-ferritin levels was
      relatively high in both groups with not always significant differences. Severe
      protein malnutrition occurred in four patients (three BPD-RYGBP and one RYGBP) (p
      = 0.37). In only one BPD-RYGBP patient (1.54%) was revision surgery to RYGBP
      necessary, due to recurrent episodes of hypoproteinemia. The remaining patients
      were treated successfully with total parenteral nutrition and nutritional
      counseling. CONCLUSIONS: Late results presented in this paper agree with the
      previously published 2-year results of the same patient cohort. Although both
      procedures are safe and effective, BPD-RYGBP seems to prevail in terms of
      successful weight loss without a significantly higher incidence of metabolic and
      non-metabolic complications.

PMID- 24105408
TI  - Postpartum translabial 2D and 3D ultrasound measurements of the anal sphincter
      complex in primiparous women delivering by vaginal birth versus Cesarean
      delivery.
AB  - INTRODUCTION AND HYPOTHESIS: Consensus on normal translabial ultrasound (TL-US)
      anal sphincter complex measurements for postpartum women is lacking. We aimed to
      evaluate normative measurements in 2D and 3D TL-US for the anal sphincter complex
      (ASC) at 6 months postpartum and compare these measurements in women who had a
      vaginal birth (VB) and in those who had a Cesarean delivery (CD). METHODS: A
      large, prospective cohort of primiparous women underwent 2D and 3D TL-US 6 months
      after their first delivery. For normative sphincter measurements, we excluded
      women with third- or fourth-degree lacerations or with sphincter interruption on
      TL-US. Measurements included the sphincter thickness at the 3, 6, 9, and 12
      o'clock positions of the external anal sphincter (EAS) and the internal anal
      sphincter (IAS) at proximal, mid, and distal levels. We also measured the mean
      coronal diameter of the pubovisceralis muscle (PVM). RESULTS: 696 women consented
      to participate, and 433 women presented for ultrasound imaging 6 months later.
      Women who sustained a third- or fourth-degree laceration had significantly
      thicker EAS measurements at 12 o'clock. Sphincter asymmetry was common (69 %),
      but was not related to mode of delivery. Only IAS measurements at the proximal
      and distal 12 o'clock position were significantly thicker for CD patients. There
      were no significant differences in the EAS or PVM measurements between VB and CD
      women. CONCLUSIONS: There appear to be few differences in normative sphincter
      ultrasound measurements between primiparous patients who had VB or CD.

PMID- 24105409
TI  - Is there a need for postoperative follow-up after routine urogynaecological
      procedures? Patients will self-present if they have problems.
AB  - INTRODUCTION AND HYPOTHESIS: The value of outpatient appointments for
      postoperative review has been questioned for many years, and the surgeon practice
      around this issue is varied. The aim of this study, as part of a larger study
      assessing postoperative follow-up, was to assess how many patients self-present
      to their general practitioner (GP) or the emergency department after surgery for
      urogynaecology procedures. METHODS: A retrospective observational study of
      postoperative urogynaecology patients between 2007 and 2012 was performed using
      the British Society of Urogynaecology (BSUG) database to identify patients. These
      records were correlated with hospital and GP records to assess whether any
      patient was seen postoperatively for a procedure-related problem. RESULTS: There
      were 244 patients with complete data on the BSUG database, of whom 25 (10 %)
      presented to hospital/secondary care in the year following their surgery; only
      three of these were admitted for problems related to their surgery. There was a
      response rate of 70 % from GPs for access to their records. This represented 171
      patients, 90 of whom (52.3 %) presented to their GP within a year of surgery
      mostly for a minor procedure-related event: 11 of these were re-referred to
      secondary care, and the remainder were treated in the community. CONCLUSIONS: The
      most important aspect of patient care is safety, and this should not be
      compromised if, for example, postoperative review were to be moved to primary
      care. As expected, this study shows that patients will self-present if they have
      problems postoperatively.

PMID- 24105410
TI  - General immune dampening is associated with disturbed metabolism at diagnosis of
      type 1 diabetes.
AB  - BACKGROUND: Type 1 diabetes (T1D) is a serious diagnosis with the prospect of
      grave short- and long-term complications and even death if poorly managed. An
      attempt has been made to describe how clinical and immunological deviations might
      influence each other close to the diagnosis of T1D. METHODS: Sixty-nine newly
      diagnosed T1D children were studied together with a reference group of 30 healthy
      children. Cytokines (interleukin (IL)-6, IL-10, IL-13, IL-17, interferon-gamma,
      and tumor necrosis factor-alpha) were detected in in vitro culture by multiplex
      fluorochrome technique. Information of clinical status of the patients such as
      BMI, weight loss, pubertal stage, duration of symptoms, previous and/or ongoing
      infections, insulin requirement, and ketoacidosis were gathered together with the
      analysis of C-peptide and glycosylated hemoglobin (HbA1c). RESULTS: In general,
      low cytokine secretion was found at diagnosis of T1D. However, high C-peptide,
      short duration of symptoms, or an infection prior to diagnosis was associated
      with increased immune activity including proinflammatory, Th2-associated, and Tr1
      associated cytokines. In contrast, ketoacidosis and later pubertal stage at onset
      of disease were more related to a Th1-prone response. CONCLUSION: There is a
      general immune dampening at diagnosis of T1D, which appears to be related to the
      metabolic state close to diagnosis.

PMID- 24105411
TI  - Change in fractional anisotropy during treatment of diabetic ketoacidosis in
      children.
AB  - BACKGROUND: The pathophysiology resulting in cerebral edema in pediatric diabetic
      ketoacidosis (DKA) is unknown. To investigate the changes in white matter
      microstructure in this disease, we measured diffusion tensor imaging (DTI)
      parameters, including apparent diffusion coefficient (ADC), fractional anisotropy
      (FA), and radial and axial diffusivity in children with DKA at two time points
      during treatment. METHODS: A prospective observational study was conducted at
      Seattle Children's Hospital, Seattle, WA. Thirty-two children admitted with DKA
      (pH < 7.3, bicarbonate < 15 mEq/l, glucose > 300 mg/dl, and ketosis; 11.9 +/- 3.2
      y; and 47% male) were enrolled and underwent two serial paired diffusion magnetic
      resonance imaging (MRI) scans following hospital admission. Seventeen of the 32
      participants had diffusion tensor images of adequate quality for tract-based
      spatial statistics (TBSS) analysis. RESULTS: TBSS mapping demonstrated main white
      matter tract areas with a significant increase in FA and areas with a significant
      decrease in ADC, from the first to the second MRI. Both radial and axial
      diffusivity terms showed change, with a diffuse pattern of involvement.
      CONCLUSION: Consistent DTI changes occurred during DKA treatment over a short
      time frame. These findings describe widespread water diffusion abnormalities in
      DKA, supporting an association between clinical illness and DTI markers of
      microstructural change in white matter.

PMID- 24105412
TI  - The mechanical properties of human adipose tissues and their relationships to the
      structure and composition of the extracellular matrix.
AB  - Adipose tissue (AT) expansion in obesity is characterized by cellular growth and
      continuous extracellular matrix (ECM) remodeling with increased fibrillar
      collagen deposition. It is hypothesized that the matrix can inhibit cellular
      expansion and lipid storage. Therefore, it is important to fully characterize the
      ECM's biomechanical properties and its interactions with cells. In this study, we
      characterize and compare the mechanical properties of human subcutaneous and
      omental tissues, which have different physiological functions. AT was obtained
      from 44 subjects undergoing surgery. Force/extension and stress/relaxation data
      were obtained. The effects of osmotic challenge were measured to investigate the
      cellular contribution to tissue mechanics. Tissue structure and its response to
      tensile strain were determined using nonlinear microscopy. AT showed nonlinear
      stress/strain characteristics of up to a 30% strain. Comparing paired
      subcutaneous and omental samples (n = 19), the moduli were lower in subcutaneous:
      initial 1.6 +/- 0.8 (means +/- SD) and 2.9 +/- 1.5 kPa (P = 0.001), final 11.7 +/
      6.4 and 32 +/- 15.6 kPa (P < 0.001), respectively. The energy dissipation
      density was lower in subcutaneous AT (n = 13): 0.1 +/- 0.1 and 0.3 +/- 0.2 kPa,
      respectively (P = 0.006). Stress/relaxation followed a two-exponential time
      course. When the incubation medium was exchanged for deionized water in specimens
      held at 30% strain, force decreased by 31%, and the final modulus increased
      significantly. Nonlinear microscopy revealed collagen and elastin networks in
      close proximity to adipocytes and a larger-scale network of larger fiber bundles.
      There was considerable microscale heterogeneity in the response to strain in both
      cells and matrix fibers. These results suggest that subcutaneous AT has greater
      capacity for expansion and recovery from mechanical deformation than omental AT. 

PMID- 24105413
TI  - Autocrine role of interleukin-13 on skeletal muscle glucose metabolism in type 2
      diabetic patients involves microRNA let-7.
AB  - Low-grade inflammation associated with type 2 diabetes (T2DM) is postulated to
      exacerbate insulin resistance. We report that serum levels, as well as IL-13
      secreted from cultured skeletal muscle, are reduced in T2DM vs. normal glucose
      tolerant (NGT) subjects. IL-13 exposure increases skeletal muscle glucose uptake,
      oxidation, and glycogen synthesis via an Akt-dependent mechanism. Expression of
      microRNA let-7a and let-7d, which are direct translational repressors of the IL
      13 gene, was increased in skeletal muscle from T2DM patients. Overexpression of
      let-7a and let-7d in cultured myotubes reduced IL-13 secretion. Furthermore,
      basal glycogen synthesis was reduced in cultured myotubes exposed to an IL-13
      neutralizing antibody. Thus, IL-13 is synthesized and released by skeletal muscle
      through a mechanism involving let-7, and this effect is attenuated in skeletal
      muscle from insulin-resistant T2DM patients. In conclusion, IL-13 plays an
      autocrine role in skeletal muscle to increase glucose uptake and metabolism,
      suggesting a role in glucose homeostasis in metabolic disease. 

PMID- 24105415
TI  - Overexpression of NF-kappaB p65 in macrophages ameliorates atherosclerosis in
      apoE-knockout mice.
AB  - The transcription factor NF-kappaB p65 is a key regulator in the regulation of an
      inflammatory response and in the pathology of atherosclerosis. However, there is
      no direct evidence for the role of NF-kappaB in macrophages in the development of
      atherosclerosis. We investigated whether macrophage overexpression of p65 in apoE
      knockout mice could improve atherosclerosis. Transgenic (Tg) mice overexpressing
      p65 in macrophages were generated by crossing fatty acid-binding protein 4 (aP2)
      promoter-controlled p65 mice with apoE-knockout (KO) mice. Tg mice exhibited
      functional activation of NF-kappaB signaling in macrophages and fat tissues. We
      observed that the atherosclerotic lesion was 40% less in the Tg mice compared
      with the apoE-KO controls fed a standard atherogenic diet for 16 wk (n = 12). The
      Tg mice were leaner from reduced fat mass by increased energy expenditure.
      Moreover, the overexpression of p65 in macrophages suppressed foam cell
      formation. Our results show that there is 1) an increased fatty acid oxidation in
      macrophages, 2) a reduced scavenger receptor CD36 expression and lipid
      accumulation in microphages, 3) reduced-inflammation cytokines in serum, and 4)
      enhanced energy expenditure in Tg mice. Our data suggest that activation of NF
      kappaB in macrophages has atheroprotective effects in mice by enhancing lipid
      metabolism and energy expenditure. 

PMID- 24105414
TI  - The food intake-suppressive effects of glucagon-like peptide-1 receptor signaling
      in the ventral tegmental area are mediated by AMPA/kainate receptors.
AB  - Glucagon-like peptide-1 receptor (GLP-1R) activation in the ventral tegmental
      area (VTA) is physiologically relevant for the control of palatable food intake.
      Here, we tested whether the food intake-suppressive effects of VTA GLP-1R
      activation are mediated by glutamatergic signaling within the VTA. Intra-VTA
      injections of the GLP-1R agonist exendin-4 (Ex-4) reduced palatable high-fat food
      intake in rats primarily by reducing meal size; these effects were mediated in
      part via glutamatergic AMPA/kainate but not NMDA receptor signaling. Additional
      behavioral data indicated that GLP-1R expressed specifically within the VTA can
      partially mediate the intake- and body weight-suppressive effects of systemically
      administered Ex-4, offering the intriguing possibility that this receptor
      population may be clinically relevant for food intake control. Intra-VTA Ex-4
      rapidly increased tyrosine hydroxylase levels within the VTA, suggesting that GLP
      1R activation modulates VTA dopaminergic signaling. Further evidence for this
      hypothesis was provided by electrophysiological data showing that Ex-4 increased
      the frequency of AMPA-mediated currents and reduced the paired/pulse ratio in VTA
      dopamine neurons. Together, these data provide novel mechanisms by which GLP-1R
      agonists in the mesolimbic reward system control for palatable food intake. 

PMID- 24105417
TI  - Synthesis, characterization and antimicrobial activity of conjugates based on
      fluoroquinolon-type antibiotics and gelatin.
AB  - Different fluoroquinolon-type antibiotics were conjugated to gelatin with the aim
      to synthesize biomacromolecules with antimicrobial properties. The covalent
      linkage of the antibiotic was performed by a radical process involving the
      residues in the side chains of gelatin able to undergo oxidative modifications.
      The conjugation of antibiotic moieties onto the protein structure was confirmed
      by FT-IR, UV-Vis, fluorescence, and calorimetric analyses. Biocompatibility tests
      were performed on human bone marrow mesenchymal stromal cells and the
      antibacterial properties of bioactive polymers were investigated by appropriate
      tests against Klebsiella pneumoniae and Escherichia coli. With regard to the
      tests conducted in the presence of E. coli, a minimum inhibitory concentration
      (MIC) ranging from 0.05 to 0.40 MUg mL(-1) was recorded, while in the presence of
      K. pneumoniae this concentration varies from 0.10 to 1.60 MUg mL(-1). In all the
      conjugates, the drug moieties retain their biological activity and the MIC values
      are lower than the resistance parameters of fluoroquinolon-type antibiotics
      versus Enterobacteriacae. The collected data suggest a broad range of
      applications, from biomedical to pharmaceutical and food science for all
      conjugates.

PMID- 24105418
TI  - Effect of para halogen modification of S-3-(phenoxy)-2-hydroxy-2-methyl-N-(4
      nitro-3-trifluoromethyl-phenyl)-propionamides on metabolism and clearance.
AB  - The purpose of this study was to better understand why para-halogen modifications
      of S-3-(4-halophenoxy)-2-hydroxy-2-methyl-N-(4-nitro-3-trifluoromethylphenyl)
      propionamide selective androgen receptor modulators (SARMs) had the opposite of
      expected effects on total clearance, in which electron-withdrawing groups
      generally protect benzene ring from hydroxylation. We determined the plasma
      protein binding of this series of halogen substituted SARMs and characterized the
      qualitative effects of B-ring halogen substitution on in vivo metabolism. In vivo
      metabolism of S-9, S-10, and S-11 were determined in rats using LC-MS(n)
      analysis. Intrinsic clearance was measured by in vitro metabolism using rat liver
      microsomes. Rat plasma protein binding was measured by equilibrium dialysis and
      drug concentrations after dialysis were analyzed by LC-MS. The major metabolic
      pathways of the halogen-substituted SARMs examined were very similar and included
      three major phase I pathways; (1) hydrolysis of the amide bond, (2) B-ring
      hydroxylation, and (3) A-ring nitro reduction to an aromatic amine. In plasma
      protein binding studies, S-1 (F, fu = 0.78 +/- 0.17 %) showed the greatest
      unbound fraction, followed by S-9 (Cl, fu = 0.10 +/- 0.04 %), S-10 (Br, fu = 0.03
      +/- 0.01 %), and S-11 (I, fu = 0.008 +/- 0.001 %). The CLint values of S-1, S-9,
      S-10, and S-11 were 2.4, 2.5, 2.8, and 4.6 MUL/min/mg, respectively. These
      findings suggest that as lipophilicity increased the free fraction was reduced
      thus compensating for metabolic liability and resulting in the apparent
      discrepancy between CLint and CL total of halogen-substituted SARMs series.

PMID- 24105419
TI  - Platycodi radix saponin inhibits alpha-glucosidase in vitro and modulates hepatic
      glucose-regulating enzyme activities in C57BL/KsJ-db/db mice.
AB  - This study investigated anti-diabetic activity of a concentrated saponin fraction
      from Platycodi radix (SK1) in C57BL/KsJ-db/db mice and its underlying mechanism.
      Mice were fed diet with 0.5 % SK1 (w/w) for 6 weeks. SK1 significantly lowered
      the blood glucose and glycosylated hemoglobin levels and improved glucose and
      insulin tolerance. The plasma and pancreatic insulin and C-peptide levels and
      fecal cholesterol content were increased, whereas plasma urea nitrogen, free
      fatty acid and triglyceride levels were decreased by SK1 supplementation.
      Glucokinase (GK) activity in the liver was significantly higher in the SK1 group
      than the control group, whereas the glucose-6-phosphatase (G6Pase) activity was
      lower. SK1 significantly down-regulated GK mRNA expression compared to the
      control group but did not affect G6Pase and glucose transporter 2 mRNA.
      Phosphoenolpyruvate carboxykinase activity and mRNA levels did not differ between
      groups. SK1 also markedly inhibited the small intestinal disaccharidases
      activities compared to those of control db/db mice. Furthermore, SK1 was a more
      effective alpha-glucosidase inhibitor than acarbose in vitro. Overall, these
      findings suggest that SK1 is a potential glucose-lowering agent that functions
      via inhibition of carbohydrate digestive enzyme activities and modulation of
      glucose-regulating enzyme activities in db/db mice.

PMID- 24105416
TI  - Molecular mechanisms that drive estradiol-dependent burst firing of Kiss1 neurons
      in the rostral periventricular preoptic area.
AB  - Kisspeptin (Kiss1) neurons in the rostral periventricular area of the third
      ventricle (RP3V) provide excitatory drive to gonadotropin-releasing hormone
      (GnRH) neurons to control fertility. Using whole cell patch clamp recording and
      single-cell (sc)RT-PCR techniques targeting Kiss1-CreGFP or tyrosine hydroxylase
      (TH)-EGFP neurons, we characterized the biophysical properties of these neurons
      and identified the critical intrinsic properties required for burst firing in
      17beta-estradiol (E2)-treated, ovariectomized female mice. One-fourth of the RP3V
      Kiss1 neurons exhibited spontaneous burst firing. RP3V Kiss1 neurons expressed a
      hyperpolarization-activated h-current (Ih) and a T-type calcium current (IT),
      which supported hyperpolarization-induced rebound burst firing. Under voltage
      clamp conditions, all Kiss1 neurons expressed a kinetically fast Ih that was
      augmented 3.4-fold by high (LH surge-producing)-E2 treatment. scPCR analysis of
      Kiss1 neurons revealed abundant expression of the HCN1 channel transcripts. Kiss1
      neurons also expressed a Ni(2+)- and TTA-P2-sensitive IT that was augmented
      sixfold with high-E2 treatment. CaV3.1 mRNA was also highly expressed in these
      cells. Current clamp analysis revealed that rebound burst firing was induced in
      RP3V Kiss1 neurons in high-E2-treated animals, and the majority of Kiss1 neurons
      had a hyperpolarization threshold of -84.7 mV, which corresponded to the
      V&frac12; for IT de-inactivation. Finally, Kiss1 neurons in the RP3V were
      hyperpolarized by MU- and kappa-opioid and GABAB receptor agonists, suggesting
      that these pathways also contribute to rebound burst firing. Therefore, Kiss1
      neurons in the RP3V express the critical channels and receptors that permit E2
      dependent rebound burst firing and provide the biophysical substrate that drives
      the preovulatory surge of GnRH. 

PMID- 24105420
TI  - Exercise-induced cardioprotection: a role for eNOS uncoupling and NO metabolites.
AB  - Exercise is an efficient strategy for myocardial protection against ischemia
      reperfusion (IR) injury. Although endothelial nitric oxide synthase (eNOS) is
      phosphorylated and activated during exercise, its role in exercise-induced
      cardioprotection remains unknown. This study investigated whether modulation of
      eNOS activation during IR could participate in the exercise-induced
      cardioprotection against IR injury. Hearts isolated from sedentary or exercised
      rats (5 weeks training) were perfused with a Langendorff apparatus and IR
      performed in the presence or absence of NOS inhibitors [N-nitro-L-arginine methyl
      ester, L-NAME or N5-(1-iminoethyl)-L-ornithine, L-NIO] or tetrahydrobiopterin
      (BH4). Exercise training protected hearts against IR injury and this effect was
      abolished by L-NAME or by L-NIO treatment, indicating that exercise-induced
      cardioprotection is eNOS dependent. However, a strong reduction of eNOS
      phosphorylation at Ser1177 (eNOS-PSer1177) and of eNOS coupling during early
      reperfusion was observed in hearts from exercised rats (which showed higher eNOS
      PSer1177 and eNOS dimerization at baseline) in comparison to sedentary rats.
      Despite eNOS uncoupling, exercised hearts had more S-nitrosylated proteins after
      early reperfusion and also less nitro-oxidative stress, indexed by lower
      malondialdehyde content and protein nitrotyrosination compared to sedentary
      hearts. Moreover, in exercised hearts, stabilization of eNOS dimers by BH4
      treatment increased nitro-oxidative stress and then abolished the exercise
      induced cardioprotection, indicating that eNOS uncoupling during IR is required
      for exercise-induced myocardial cardioprotection. Based on these results, we
      hypothesize that in the hearts of exercised animals, eNOS uncoupling associated
      with the improved myocardial antioxidant capacity prevents excessive NO synthesis
      and limits the reaction between NO and O2.- to form peroxynitrite (ONOO-), which
      is cytotoxic.

PMID- 24105421
TI  - Let's sp(l)ice up pluripotency!

PMID- 24105422
TI  - Postoperative pancreatic fistula formation according to ISGPF criteria after D2
      gastrectomy in Western patients.
AB  - BACKGROUND: Limited information is available on the incidence of postoperative
      pancreatic fistula (POPF) after D2 gastrectomy with the strict use of the
      International Study Group of Pancreatic Fistula (ISGPF) criteria, particularly so
      in Western patients. METHODS: All patients who underwent gastrectomy for
      adenocarcinoma at the Karolinska University Hospital Huddinge from 2006 until
      June 2012 were identified via hospital records and reviewed for type of surgical
      procedure, postoperative morbidity, incidence, and risk factors for POPF.
      RESULTS: Ninety-two of 107 cases had a D2 gastrectomy eligible for evaluation of
      POPF, of which 83 (90 %) also underwent bursectomy. Seven patients fulfilled the
      criteria for POPF grade A (7.6 %), 5 met the criteria for POPF grade B (5.4 %),
      and 6 the criteria for POPF grade C (6.5 %). The incidence of POPF grade B or C
      was 4.9 % among the 82 patients for whom no pancreatic resection was performed
      and 70 % among 10 cases with concomitant pancreatic resection. The latter (OR
      156.2, 95 % CI 8.00-3046.93) and age (OR 1.2, 95 % CI 1.02-1.35) were found to be
      the only risk factors for POPF after gastrectomy upon a multivariate analysis.
      CONCLUSIONS: In this series of Western patients, POPF grade B or C according to
      the ISGPF criteria was uncommon after D2 gastrectomy without pancreatic
      resection. Bursectomy was not a risk factor for POPF.

PMID- 24105423
TI  - Conformational change of Sos-derived proline-rich peptide upon binding Grb2 N
      terminal SH3 domain probed by NMR.
AB  - Growth factor receptor-bound protein 2 (Grb2) is a small adapter protein composed
      of a single SH2 domain flanked by two SH3 domains. The N-terminal SH3 (nSH3)
      domain of Grb2 binds a proline-rich region present in the guanine nucleotide
      releasing factor, son of sevenless (Sos). Using NMR relaxation dispersion and
      chemical shift analysis methods, we investigated the conformational change of the
      Sos-derived proline-rich peptide during the transition between the free and Grb2
      nSH3-bound states. The chemical shift analysis revealed that the peptide does not
      present a fully random conformation but has a relatively rigid structure. The
      relaxation dispersion analysis detected conformational exchange of several
      residues of the peptide upon binding to Grb2 nSH3. 

PMID- 24105424
TI  - Beclometasone for chronic obstructive pulmonary disease.
AB  - BACKGROUND: Chronic obstructive pulmonary disease (COPD) is a chronic obstructive
      lung condition, diagnosed in patients with dyspnoea, chronic cough or sputum
      production and/or a history of risk factor exposure, if their postbronchodilator
      forced expiratory lung volume in 1 second (FEV1)/forced vital lung capacity (FVC)
      ratio is less than 0.70, according to the international GOLD (Global Initiative
      for Obstructive Lung Disease) criteria.Inhaled corticosteroid (ICS) medications
      are now recommended for COPD only in combination treatment with long-acting beta2
      agonists (LABAs), and only for patients of GOLD stage 3 and stage 4 severity, for
      both GOLD groups C and D.ICS are expensive and how effective they are is a topic
      of controversy, particularly in relation to their adverse effects (pneumonia),
      which may be linked to more potent ICS. It is unclear whether beclometasone
      dipropionate (BDP), an unlicensed but widely used inhaled steroid, is a safe and
      effective alternative to other ICS. OBJECTIVES: To determine the effectiveness
      and safety in COPD of inhaled beclometasone alone compared with placebo, and of
      inhaled beclometasone in combination with LABAs compared with LABAs alone. SEARCH
      METHODS: We searched the Cochrane Airways Group Specialised Register of trials
      (CAGR) (includes Cochrane Central Register of Controlled Trials (CENTRAL),
      MEDLINE, EMBASE, CINAHL, AMED and PsycINFO, and handsearching of respiratory
      journals and meeting abstracts) (February 2013), conference abstracts, ongoing
      studies and reference lists of articles. We contacted pharmaceutical companies
      and drug marketing authorisation bodies/ethics committees in 49 countries and
      obtained licensing information. SELECTION CRITERIA: Randomised controlled trials
      of BDP compared with placebo, or BDP/LABA compared with LABA, in stable COPD.
      Minimum trial duration is 12 weeks. DATA COLLECTION AND ANALYSIS: Inclusion, bias
      assessment and data extraction were conducted by two review authors
      independently. The analysis was performed by one review author. Study authors
      were contacted to obtain missing information. MAIN RESULTS: For BDP versus
      placebo, two studies were included, of which one trial (participants n = 194) was
      included in the quantitative analysis. This study was a very high-dose trial with
      stable stage 2 and 3 COPD participants. No statistically significant results in
      change in lung function, mortality, exacerbations, dyspnoea scores or withdrawal
      were obtained. The quality of the evidence of all these outcomes was graded low
      to very low. Data on risk of pneumonia were lacking.The main focus of the review
      was the more clinically relevant BDP/LABA versus LABA arm. Therefore the findings
      are reported more fully.For BDP/LABA versus LABA, one study (n = 474) was
      included, with a further ongoing study identified for future inclusion. The
      included trial was a high-dose study of stable stage 3 COPD participants.
      Compared with LABA, people receiving BDP/LABA showed a statistically significant
      improvement in FEV1 lung function measurements of 0.051 L (95% confidence
      Interval (CI) 0.001 to 0.102, P = 0.046) (high quality of evidence) and in (self
      reported) days without rescue bronchodilators (mean difference 7.05, 95% CI 0.84
      to 13.26, P = 0.03) (low quality), both of which are unlikely to be clinically
      significant. Participants receiving BDP/LABA also had a statistically significant
      increased rate of exacerbations leading to hospitalisation (risk ratio (RR) 1.84,
      95% CI 1.17 to 2.90, P = 0.008) (moderate quality), although this finding is
      debatable as this study's post hoc analysis showed no statistically significant
      difference when accounting for country-specific differences in hospitalisation
      policies. We did not find statistically significant differences for mortality
      (very low quality), pneumonia (low quality), exacerbations, exercise capacity,
      quality of life and dyspnoea scores, adverse events and withdrawal (all moderate
      quality). AUTHORS' CONCLUSIONS: We found little evidence to suggest that
      beclometasone is a safer or more effective treatment option for people with COPD
      when compared with placebo or when used in combination with LABA; when
      statistically significant differences were found, they mostly were not clinically
      meaningful or were based on data from only one study. The review was limited by
      an inability to obtain data from one study and likely publication bias for BDP
      versus placebo, and by the inclusion of one study only for BDP/LABA versus LABA.
      An ongoing study of BDP/LABA versus LABA may have a further impact on these
      conclusions.

PMID- 24105425
TI  - Shifts of visuospatial attention do not cause the spatial distortions of the
      Roelofs effect.
AB  - When a visible frame is offset left or right of an observer's objective midline,
      subjective midline is pulled toward the frame's center, resulting in an illusion
      of perceived space known as the Roelofs effect. However, a large frame is not
      necessary to generate the effect-even a small peripheral stimulus is sufficient,
      raising the possibility that the effect would be brought about by any stimulus
      that draws attention away from the midline. To assess the relationship between
      attention and distortions of perceived space, we adopted a paradigm that included
      a spatial cue that attracted the participant's attention, and an occasional probe
      whose location was to be reported. If shifts of attention cause the Roelofs
      effect, the probe's perceived location should vary with the locus of attention.
      Exogenous attentional cues caused a Roelofs-like effect, but these cues created
      an asymmetry in the visual display that may have driven the effect directly. In
      contrast, there was no mislocation after endogenous cues that contained no
      asymmetry in the visual display. A final experiment used color-contingent
      attentional cues to eliminate the confound between cue location and asymmetry in
      the visual display, and provided a clear demonstration that the Roelofs effect is
      caused by an asymmetric visual display, independent of any shift of attention. 

PMID- 24105426
TI  - Optical coherence tomography monitoring of enhanced skin optical clearing in rats
      in vivo.
AB  - A comparative study of physical, chemical, and combined enhancement of
      transdermal transport of optical clearing agents (OCAs) is presented. As a
      physical enhancer of diffusivity, ultrasound (US) with a frequency 1 MHz and a
      power 1.1 W in the continuous mode was used, and dimethyl sulfoxide (DMSO) was
      used as a chemical enhancer. OCA (glycerol and polyethylene glycol-400 in equal
      proportion) was topically applied to the rat skin in vivo as alone or as together
      with the enhancers. Monitoring of skin optical clearing was implemented using an
      optical coherence tomography. The results have shown that the attenuation
      coefficient of intact skin dermis after the application of US-DMSO-OCA, US-OCA
      (both for 4 min), and DMSO-OCA (for 20 min) combinations decreased approximately
      by 31%, 19%, and 5%, respectively, while OCA alone did not induce a noticeable
      clearing effect for 20 min. Control skin sites with removed epidermis were used
      for modeling the upper limit of dermis optical clearing, i.e., maximal degree of
      optical clearing, by using the studied enhancers. They demonstrated that the
      attenuation coefficient decreases by 32%, 30%, 17%, and 16% at the action of US
      DMSO-OCA, US-OCA, DMSO-OCA, and OCA, respectively. It can be concluded that US
      DMSO-OCA combination only allowed reaching the upper limit of skin optical
      clearing.

PMID- 24105427
TI  - Comparative in vitro study and biomechanical testing of two different magnesium
      alloys.
AB  - In this in vitro study, magnesium plates of ZEK100 and MgCa0.8 alloy similar to
      common titanium alloy osteosynthesis plates were investigated as degradable
      biomedical materials with a focus on primary stability. Immersion tests were
      performed in Hank's Balanced Salt Solution at 37. The bending strength of the
      samples was determined using the four-point bending test according to ISO
      9585:1990. The initial strength of the noncorroded ZEK100 plate was 11% greater
      than that of the MgCa0.8 plate; both were approximately 65% weaker than a
      titanium plate. The bending strength was determined after 48 and 96 h of
      immersion in Hank's Balanced Salt Solution; both magnesium alloys decreased by
      approximately 7% after immersion for 96 h. The degradation rate and the Mg(2+)
      release of ZEK100 were lower than those of MgCa0.8. Strong pitting and filiform
      corrosion were observed in the MgCa0.8 samples after 96 h of immersion. The
      surface of the ZEK100 plates exhibited only small areas of filiform corrosion.
      The results of this in vitro study indicate that the ZEK100 alloy may be more
      suitable for biomedical applications.

PMID- 24105428
TI  - Gelatin powders accelerate the resorption of calcium phosphate cement and improve
      healing in the alveolar ridge.
AB  - The aim of this study was to show the effectiveness of combining calcium
      phosphate cement and gelatin powders to promote bone regeneration in the canine
      mandible. We mixed gelatin powders with calcium phosphate cement to create a
      macroporous composite. In four beagle dogs, two saddle-type bone defects were
      created on each side of the mandible, and calcium phosphate cement alone or
      calcium phosphate cement containing composite gelatin powders was implanted in
      each of the defects. After a healing period of six months, mandibles were removed
      for uCT and histological analyses. The uCT and histological analyses showed that
      at experimental sites at which calcium phosphate cement alone had been placed new
      bone had formed only around the periphery of the residual calcium phosphate
      cement and that there had been little or no ingrowth into the calcium phosphate
      cement. On the other hand, at experimental sites at which calcium phosphate
      cement containing composite gelatin powders had been placed, we observed
      regenerated new bone in the interior of the residual calcium phosphate cement as
      well as around its periphery. The amount of resorption of calcium phosphate
      cement and bone regeneration depended on the mixing ratio of gelatin powders to
      calcium phosphate cement. New bone replacement was significantly better in the
      sites treated with calcium phosphate cement containing composite gelatin powders
      than in those treated with calcium phosphate cement alone. 

PMID- 24105429
TI  - Cytotoxic agents are detrimental to bone formed by distraction osteogenesis.
AB  - Distraction osteogenesis can be used to replace segmental bone loss when treating
      malignant bone tumors in children and adolescents. These patients often receive
      cytotoxic chemotherapy as part of their treatment regimen. The effect of
      cytotoxic drugs on the cellular processes during distraction osteogenesis and the
      structural and mechanical properties of regenerate bone is unknown. We therefore
      used a rabbit model of distraction osteogenesis to determine that cytotoxic
      agents had a detrimental effect on regenerate bone formed by this technique. We
      administered adriamycin and cisplatinum to 20 rabbits using two different
      simulated chemotherapy regimens. All rabbits underwent an osteotomy at 12 weeks
      of age. Distraction osteogenesis began 24 h later at a rate of 0.75 mm a day for
      10 days, followed by 18 days without correction to allow for consolidation.
      Regenerate bone was assessed using plain radiographs, bone densitometry, and
      mechanical testing. Peri-operative chemotherapy decreased the mechanical
      properties of the regenerate with regard to yield strain (3.7 * 10(-2) vs. 5.2 *
      10(-2)) and energy at yield (2.73 * 10(7) vs. 3.92 * 10(7)). Preoperative
      chemotherapy in isolation reduced bone mineral density (0.38 vs. 0.5 g/cm(2)),
      bone mineral content (0.24 vs. 0.36 g), and volumetric bone mineral density (0.57
      vs. 0.65 g/cm(2)) with no alterations in the mechanical properties. CONCLUSIONS:
      Preoperative chemotherapy appears to decrease the volume of regenerate bone,
      without affecting structural integrity, suggesting that the callus formed is of
      good quality. The converse appears true for peri-operative chemotherapy.

PMID- 24105430
TI  - RGS2 regulates urotensin II-induced intracellular Ca2+ elevation and contraction
      in glomerular mesangial cells.
AB  - Urotensin II (UII), a vasoactive peptide modulates renal hemodynamics. However,
      the physiological functions of UII in glomerular cells are unclear. In
      particular, whether UII alters mesangial tone remains largely unknown. The
      present study investigates the physiological effects of UII on glomerular
      mesangial cells (GMCs). This study also tested the hypothesis that the regulator
      of G-protein signaling (RGS) controls UII receptor (UTR) activity in GMCs. RT
      PCR, Western immunoblotting, and immunofluorescence revealed UTR expression in
      cultured murine GMCs. Mouse UII (mUII) stimulated Ca(2+) release from
      intracellular stores and activated store-operated Ca(2+) entry (SOCE) in the
      cells. mUII also caused a reduction in planar GMC surface area. mUII-induced
      [Ca(2+)]i elevation and contraction were attenuated by SB 657510, a UTR
      antagonist, araguspongin B, an inositol 1,4,5-trisphosphate receptor antagonist,
      thapsigargin, a sarco/endoplasmic reticulum Ca(2+)-ATPase inhibitor, and La(3+),
      a store-operated Ca(2+) channel blocker, but not nimodipine, an L-type Ca(2+)
      channel blocker. In situ proximity ligation assay indicated molecular proximity
      between endogenous RGS2 and UTR in the cells. Treatment of GMCs with mUII
      elevated plasma membrane expression of RGS2 by ~2-fold. mUII also increased the
      interaction between RGS2 and UTR in the cells. siRNA-mediated knockdown of RGS2
      in murine GMCs increased mUII-induced [Ca(2+)]i elevation and contraction by ~35
      and 31%, respectively. These findings indicate that mUII-induced SOCE results in
      murine GMC contraction. These data also suggest that UTR activation stimulates
      RGS2 recruitment to GMC plasma membrane as a negative feedback mechanism to
      regulate UTR signaling.

PMID- 24105431
TI  - Performance of risk assessment instruments for predicting osteoporotic fracture
      risk: a systematic review.
AB  - We systematically reviewed the literature on the performance of osteoporosis
      absolute fracture risk assessment instruments. Relatively few studies have
      evaluated the calibration of instruments in populations separate from their
      development cohorts, and findings are mixed. Many studies had methodological
      limitations making susceptibility to bias a concern. INTRODUCTION: The aim of
      this study was to systematically review the literature on the performance of
      osteoporosis clinical fracture risk assessment instruments for predicting
      absolute fracture risk, or calibration, in populations other than their
      derivation cohorts. METHODS: We performed a systematic review, and MEDLINE,
      Embase, Cochrane Library, and multiple other literature sources were searched.
      Inclusion and exclusion criteria were applied and data extracted, including
      information about study participants, study design, potential sources of bias,
      and predicted and observed fracture probabilities. RESULTS: A total of 19,949
      unique records were identified for review. Fourteen studies met inclusion
      criteria. There was substantial heterogeneity among included studies. Six studies
      assessed the WHO's Fracture Risk Assessment (FRAX) instrument in five separate
      cohorts, and a variety of risk assessment instruments were evaluated in the
      remainder of the studies. Approximately half found good instrument calibration,
      with observed fracture probabilities being close to predicted probabilities for
      different risk categories. Studies that assessed the calibration of FRAX found
      mixed performance in different populations. A similar proportion of studies that
      evaluated simple risk assessment instruments (<=5 variables) found good
      calibration when compared with studies that assessed complex instruments (>5
      variables). Many studies had methodological features making them susceptible to
      bias. CONCLUSIONS: Few studies have evaluated the performance or calibration of
      osteoporosis fracture risk assessment instruments in populations separate from
      their development cohorts. Findings are mixed, and many studies had
      methodological limitations making susceptibility to bias a possibility, raising
      concerns about use of these tools outside of the original derivation cohorts.
      Further studies are needed to assess the calibration of instruments in different
      populations prior to widespread use.

PMID- 24105432
TI  - Amplitudes and time scales of picosecond-to-microsecond motion in proteins
      studied by solid-state NMR: a critical evaluation of experimental approaches and
      application to crystalline ubiquitin.
AB  - Solid-state NMR provides insight into protein motion over time scales ranging
      from picoseconds to seconds. While in solution state the methodology to measure
      protein dynamics is well established, there is currently no such consensus
      protocol for measuring dynamics in solids. In this article, we perform a detailed
      investigation of measurement protocols for fast motions, i.e. motions ranging
      from picoseconds to a few microseconds, which is the range covered by dipolar
      coupling and relaxation experiments. We perform a detailed theoretical
      investigation how dipolar couplings and relaxation data can provide information
      about amplitudes and time scales of local motion. We show that the measurement of
      dipolar couplings is crucial for obtaining accurate motional parameters, while
      systematic errors are found when only relaxation data are used. Based on this
      realization, we investigate how the REDOR experiment can provide such data in a
      very accurate manner. We identify that with accurate rf calibration, and explicit
      consideration of rf field inhomogeneities, one can obtain highly accurate
      absolute order parameters. We then perform joint model-free analyses of 6
      relaxation data sets and dipolar couplings, based on previously existing, as well
      as new data sets on microcrystalline ubiquitin. We show that nanosecond motion
      can be detected primarily in loop regions, and compare solid-state data to
      solution-state relaxation and RDC analyses. The protocols investigated here will
      serve as a useful basis towards the establishment of a routine protocol for the
      characterization of ps-MUs motions in proteins by solid-state NMR.

PMID- 24105433
TI  - High-functioning autism spectrum disorder as a basic disorder in adult psychiatry
      and psychotherapy: psychopathological presentation, clinical relevance and
      therapeutic concepts.
AB  - Autism spectrum disorder (ASD) is characterized by deficits in social cognition
      and competence, communication, highly circumscribed interests and a strong desire
      for routines. Besides, there are specific abnormalities in perception and
      language. Typical symptoms are already present in early childhood. Traditionally
      autism has been regarded as a severe form of neurodevelopmental disorder which
      goes along with overtly abnormal language, learning difficulties and low IQ in
      the majority of cases. However, over the last decades, it has become clear that
      there are also many patients with high-functioning variants of ASD. These are
      patients with normal language at a superficial level of description and normal
      and sometimes above average intelligence. In high-functioning variants of the
      disease, they may run unrecognized until late in adult life. High-functioning ASD
      is associated with a very high prevalence of comorbid classical psychiatric
      disorders such as depression, anxiety, ADHD, tics, psychotic symptoms or
      emotionally unstable syndromes. In many such cases, there is a causal
      relationship between ASD and the comorbid psychiatric conditions in that the
      specific ASD symptoms result in chronic conflicts, misunderstandings and failure
      in private and vocational relationships. These problems in turn often lead to
      depression, anxiety and sometimes psychosis-like stress reactions. In this
      constellation, ASD has to be regarded as a basic disorder with causal relevance
      for secondary psychiatric syndromes. In this paper, we summarize the classical
      presentation of high-functioning ASD in adult psychiatry and psychotherapy and
      suggest a nosological model to classify different ASD conditions instead. To
      conclude, we outline first treatment concepts in out- and in-patient settings. 

PMID- 24105434
TI  - Diagnostic value of "bedside ultrasonography" and the "water bath technique" in
      distal forearm, wrist, and hand bone fractures.
AB  - Bedside ultrasonography (BUS) has been widely used in many emergency evaluations,
      but the technique was not thoroughly evaluated for use in adult fractures. The
      water bath technique (WBT) is a modality which overcomes some important
      limitations of using BUS in extremity fractures. The study aims to evaluate and
      compare diagnostic values of BUS and WBT. The sensitivity, specificity, positive
      and negative predictive values (PPV and NPV), positive and negative likelihood
      ratios (LR+ and LR-), and accuracy of BUS and WBT were calculated and compared by
      the McNemar chi-square test. BUS had the highest sensitivity, specificity, PPV,
      and LR+ in the distal forearm. The highest NPV and LR- of BUS were seen in
      phalangeal and wrist injuries, respectively. The WBT examination had the highest
      sensitivity in phalangeal injuries and the highest specificity, PPV, and LR+ in
      the distal forearm. The highest NPV and LR- of the WBT examination were seen in
      phalangeal and wrist injuries, respectively. The McNemar chi (2) values for the
      comparison of BUS and WBT indicate that the two techniques provide statistically
      different results. The ultrasound revealed excellent diagnostic values which make
      it a favorable alternative in evaluating upper extremity fractures in adults. The
      WBT provides even better results. 

PMID- 24105435
TI  - Comparison of carotid artery stenting and carotid endarterectomy in patients with
      symptomatic carotid artery stenosis: a single center study.
AB  - INTRODUCTION: Carotid artery stenting (CAS) is believed to be an alternative to
      carotid endarterectomy (CEA); however, recent studies have demonstrated an
      increase of complications with stenting that does not reflect our experience. We
      thus wanted to compare the periprocedural and 1-year follow-up outcomes of CAS
      with those of CEA among patients with symptomatic extracranial carotid stenosis
      in a population from eastern Turkey. METHODS: The hospital records of all
      patients who underwent carotid artery revascularization were retrospectively
      reviewed. Patients were divided into two groups based on the type of carotid
      revascularization performed, namely CEA or CAS. Comparisons were made with
      respect to 30-day and 1-year outcomes of transient ischemic attack (TIA),
      myocardial infarction (MI), stroke, and all-cause death rates. Composite
      endpoints for both groups were also analyzed. RESULTS: Thirty-two CEA and 33 CAS
      procedures were performed for symptomatic occlusive carotid disease. Baseline
      characteristics were similar between both groups except for the incidence of
      diabetes mellitus. No significant differences were found with respect to 30-day
      mortality, MI, and neurologic morbidity endpoints for CEA and CAS procedures. In
      the postprocedural 1-year follow-up, only TIA was observed to be significantly
      higher in the CAS group; the other endpoints did not differ significantly. One
      year composite endpoints did not differ between both groups (log-rank P = 0.300).
      CONCLUSION: In our trial of patients with symptomatic carotid artery stenosis, no
      significant difference could be shown in periprocedural outcomes, postprocedural
      outcomes except TIA, and in composite endpoints between the CEA and CAS groups.
      CAS is a safe and efficacious alternative for the treatment of symptomatic
      carotid artery stenosis.

PMID- 24105436
TI  - Genetic mapping of sterile genes with epistasis in backcross designs.
AB  - The mapping of sterile genes is an essential issue, which should be solved for
      the investigation of sterility mechanism in wide hybridization of plants.
      However, the methods formerly developed cannot address the problem of mapping
      sterile loci with epistasis. In this study, we developed a new method to map
      sterile genes with epistasis in wide hybridizations of plants using a backcross
      design. The maximum likelihood method was used to estimate the parameters of
      recombination fractions and effects of sterile genes, and the convergent results
      of these parameters were obtained using the expectation maximization (EM)
      algorithm. The application and efficiency of this method were tested and
      demonstrated by a set of simulated data and real data analysis. Results from the
      simulation experiments showed that the method works well for simultaneously
      estimating the positions and effects of sterile genes, as well as the epistasis
      between sterile genes. A real data set of a backcross (BC) population from an
      interspecific hybrid between cultivated rice, Oryza sativa, and its wild African
      relative, Oryza longistaminata, was analyzed using the new method. Five sterile
      genes were detected on the chromosomes of 1, 3, 6, 8 and 10, and significant
      epistatic effects were found among the four pairs of sterile genes.

PMID- 24105437
TI  - Pollen flow in fragmented landscapes maintains genetic diversity following stand
      replacing disturbance in a neotropical pioneer tree, Vochysia ferruginea Mart.
AB  - In forests with gap disturbance regimes, pioneer tree regeneration is typically
      abundant following stand-replacing disturbances, whether natural or
      anthropogenic. Differences in pioneer tree density linked to disturbance regime
      can influence pollinator behaviour and impact on mating patterns and genetic
      diversity of pioneer populations. Such mating pattern shifts can manifest as
      higher selfing rates and lower pollen diversity in old growth forest populations.
      In secondary forest, where more closely related pollen donors occur, an increase
      in biparental inbreeding is a potential problem. Here, we investigate the
      consequences of secondary forest colonisation on the mating patterns and genetic
      diversity of open-pollinated progeny arrays for the long-lived, self-compatible
      pioneer tree, Vochysia ferruginea, at two Costa Rican sites. Five microsatellite
      loci were screened across adult and seed cohorts from old growth forest with
      lower density, secondary forest with higher density, and isolated individual
      trees in pasture. Progeny from both old growth and secondary forest contexts were
      predominantly outcrossed (tm=1.00) and experienced low levels of biparental
      inbreeding (tm-ts=0.00-0.04). In contrast to predictions, our results indicated
      that the mating patterns of V. ferruginea are relatively robust to density
      differences between old growth and secondary forest stands. In addition, we
      observed that pollen-mediated gene flow possibly maintained the genetic diversity
      of open-pollinated progeny arrays in stands of secondary forest adults. As part
      of a natural resource management strategy, we suggest that primary forest
      remnants should be prioritised for conservation to promote restoration of genetic
      diversity during forest regeneration. 

PMID- 24105438
TI  - Prediction of heterosis using genome-wide SNP-marker data: application to egg
      production traits in white Leghorn crosses.
AB  - Prediction of heterosis has a long history with mixed success, partly due to low
      numbers of genetic markers and/or small data sets. We investigated the prediction
      of heterosis for egg number, egg weight and survival days in domestic white
      Leghorns, using ~400 000 individuals from 47 crosses and allele frequencies on
      ~53 000 genome-wide single nucleotide polymorphisms (SNPs). When heterosis is due
      to dominance, and dominance effects are independent of allele frequencies,
      heterosis is proportional to the squared difference in allele frequency (SDAF)
      between parental pure lines (not necessarily homozygous). Under these
      assumptions, a linear model including regression on SDAF partitions crossbred
      phenotypes into pure-line values and heterosis, even without pure-line
      phenotypes. We therefore used models where phenotypes of crossbreds were
      regressed on the SDAF between parental lines. Accuracy of prediction was
      determined using leave-one-out cross-validation. SDAF predicted heterosis for egg
      number and weight with an accuracy of ~0.5, but did not predict heterosis for
      survival days. Heterosis predictions allowed preselection of pure lines before
      field-testing, saving ~50% of field-testing cost with only 4% loss in heterosis.
      Accuracies from cross-validation were lower than from the model-fit, suggesting
      that accuracies previously reported in literature are overestimated. Cross
      validation also indicated that dominance cannot fully explain heterosis.
      Nevertheless, the dominance model had considerable accuracy, clearly greater than
      that of a general/specific combining ability model. This work also showed that
      heterosis can be modelled even when pure-line phenotypes are unavailable. We
      concluded that SDAF is a useful predictor of heterosis in commercial layer
      breeding. 

PMID- 24105439
TI  - Could interallelic interactions be a key to the epigenetic aspects of fitness
      trait inbreeding depression?

PMID- 24105440
TI  - Extensive mitochondrial introgression in North American Great Black-backed Gulls
      (Larus marinus) from the American Herring Gull (Larus smithsonianus) with little
      nuclear DNA impact.
AB  - Recent genetic studies have shown that introgression rates among loci may greatly
      vary according to their location in the genome. In particular, several cases of
      mito-nuclear discordances have been reported for a wide range of organisms. In
      the present study, we examine the causes of discordance between mitochondrial
      (mtDNA) and nuclear DNA introgression detected in North American populations of
      the Great Black-backed Gull (Larus marinus), a Holarctic species, from the
      Nearctic North American Herring Gull (Larus smithsonianus). Our results show that
      extensive unidirectional mtDNA introgression from Larus smithsonianus into Larus
      marinus in North America cannot be explained by ancestral polymorphism but most
      likely results from ancient hybridization events occurring when Larus marinus
      invaded the North America. Conversely, our nuclear DNA results based on 12
      microsatellites detected very little introgression from Larus smithsonianus into
      North American Larus marinus. We discuss these results in the framework of
      demographic and selective mechanisms that have been postulated to explain mito
      nuclear discrepancies. We were unable to demonstrate selection as the main cause
      of mito-nuclear introgression discordance but cannot dismiss the possible role of
      selection in the observed pattern. Among demographic explanations, only drift in
      small populations and bias in mate choice in an invasive context may explain our
      results. As it is often difficult to demonstrate that selection may be the main
      factor driving the introgression of mitochondrial DNA in natural populations, we
      advocate that evaluating alternative demographic neutral hypotheses may help to
      indirectly support or reject hypotheses invoking selective processes. 

PMID- 24105441
TI  - Upregulated dynorphin opioid peptides mediate alcohol-induced learning and memory
      impairment.
AB  - The dynorphin opioid peptides control glutamate neurotransmission in the
      hippocampus. Alcohol-induced dysregulation of this circuit may lead to
      impairments in spatial learning and memory. This study examines whether changes
      in the hippocampal dynorphin and glutamate systems are related, and contribute to
      impairment of spatial learning and memory in a rat model of cognitive deficit
      associated with alcohol binge drinking. Hippocampal dynorphins (radioimmunoassay)
      and glutamate (in vivo microdialysis) were analyzed in Wistar rats exposed to
      repeated moderate-dose ethanol bouts that impair spatial learning and memory in
      the Water Maze Task (WMT). The highly selective, long-acting kappa-opioid
      receptor (KOR) antagonist nor-binaltorphimine (nor-BNI) was administered
      systemically or into the hippocampal CA3 region to test a role of dynorphins in
      alcohol-induced dysregulations in glutamate neurotransmission and behavior in the
      WMT. The ethanol treatment impaired learning and memory, upregulated dynorphins
      and increased glutamate overflow in the CA3 region. Administration of nor-BNI
      after cessation of ethanol exposure reversed ethanol-induced changes in glutamate
      neurotransmission in animals exposed to ethanol and normalized their performance
      in the WMT. The findings suggest that impairments of spatial learning and memory
      by binge-like ethanol exposure are mediated through the KOR activation by
      upregulated dynorphins resulting in elevation in glutamate levels. Selective KOR
      antagonists may correct alcohol-induced pathological processes, thus representing
      a novel pharmacotherapy for treating of ethanol-related cognitive deficits. 

PMID- 24105442
TI  - Seasonal variation of serotonin turnover in human cerebrospinal fluid, depressive
      symptoms and the role of the 5-HTTLPR.
AB  - Studying monoaminergic seasonality is likely to improve our understanding of
      neurobiological mechanisms underlying season-associated physiological and
      pathophysiological behavior. Studies of monoaminergic seasonality and the
      influence of the serotonin-transporter-linked polymorphic region (5-HTTLPR) on
      serotonin seasonality have yielded conflicting results, possibly due to lack of
      power and absence of multi-year analyses. We aimed to assess the extent of
      seasonal monoamine turnover and examined the possible involvement of the 5
      HTTLPR. To determine the influence of seasonality on monoamine turnover, 5
      hydroxyindoleacetic acid (5-HIAA) and homovanillic acid (HVA) were measured in
      the cerebrospinal fluid of 479 human subjects collected during a 3-year period.
      Cosine and non-parametric seasonal modeling were applied to both metabolites. We
      computed serotonin (5-HT) seasonality values and performed an association
      analysis with the s/l alleles of the 5-HTTLPR. Depressive symptomatology was
      assessed using the Beck Depression Inventory-II. Circannual variation in 5-HIAA
      fitted a spring-peak cosine model that was significantly associated with sampling
      month (P=0.0074). Season of sampling explained 5.4% (P=1.57 * 10(-7)) of the
      variance in 5-HIAA concentrations. The 5-HTTLPR s-allele was associated with
      increased 5-HIAA seasonality (standardized regression coefficient=0.12, P=0.020,
      N=393). 5-HIAA seasonality correlated with depressive symptoms (Spearman's
      rho=0.13, P=0.018, N=345). In conclusion, we highlight a dose-dependent
      association of the 5-HTTLPR with 5-HIAA seasonality and a positive correlation
      between 5-HIAA seasonality and depressive symptomatology. The presented data set
      the stage for follow-up in clinical populations with a role for seasonality, such
      as affective disorders. 

PMID- 24105443
TI  - Altered fusiform connectivity during processing of fearful faces in social
      anxiety disorder.
AB  - Social anxiety disorder (SAD) has been associated with hyper-reactivity in limbic
      brain regions like the amygdala, both during symptom provocation and emotional
      face processing tasks. In this functional magnetic resonance imaging study we
      sought to examine brain regions implicated in emotional face processing, and the
      connectivity between them, in patients with SAD (n=14) compared with healthy
      controls (n=12). We furthermore aimed to relate brain reactivity and connectivity
      to self-reported social anxiety symptom severity. SAD patients exhibited hyper
      reactivity in the bilateral fusiform gyrus in response to fearful faces, as well
      as greater connectivity between the fusiform gyrus and amygdala, and decreased
      connectivity between the fusiform gyrus and ventromedial prefrontal cortex.
      Within the SAD group, social anxiety severity correlated positively with amygdala
      reactivity to emotional faces, amygdala-fusiform connectivity and connectivity
      between the amygdala and superior temporal sulcus (STS). These findings point to
      a pivotal role for the fusiform gyrus in SAD neuropathology, and further suggest
      that altered amygdala-fusiform and amygdala-STS connectivity could underlie
      previous findings of aberrant socio-emotional information processing in this
      anxiety disorder. 

PMID- 24105444
TI  - Maternal positions and mobility during first stage labour.
AB  - BACKGROUND: It is more common for women in both high- and low-income countries
      giving birth in health facilities, to labour in bed. There is no evidence that
      this is associated with any advantage for women or babies, although it may be
      more convenient for staff. Observational studies have suggested that if women lie
      on their backs during labour this may have adverse effects on uterine
      contractions and impede progress in labour, and in some women reduce placental
      blood flow. OBJECTIVES: To assess the effects of encouraging women to assume
      different upright positions (including walking, sitting, standing and kneeling)
      versus recumbent positions (supine, semi-recumbent and lateral) for women in the
      first stage of labour on duration of labour, type of birth and other important
      outcomes for mothers and babies. SEARCH METHODS: We searched the Cochrane
      Pregnancy and Childbirth Group's Trials Register (31 January 2013). SELECTION
      CRITERIA: Randomised and quasi-randomised trials comparing women randomised to
      upright versus recumbent positions in the first stage of labour. DATA COLLECTION
      AND ANALYSIS: We used methods described in the Cochrane Handbook for Systematic
      Reviews of Interventions for carrying out data collection, assessing study
      quality and analysing results. Two review authors independently evaluated
      methodological quality and extracted data for each study. We sought additional
      information from trial authors as required. We used random-effects analysis for
      comparisons in which high heterogeneity was present. We reported results using
      the average risk ratio (RR) for categorical data and mean difference (MD) for
      continuous data. MAIN RESULTS: Results should be interpreted with caution as the
      methodological quality of the 25 included trials (5218 women) was variable.For
      Comparison 1: Upright and ambulant positions versus recumbent positions and bed
      care, the first stage of labour was approximately one hour and 22 minutes shorter
      for women randomised to upright as opposed to recumbent positions (average MD 
      1.36, 95% confidence interval (CI) -2.22 to -0.51; 15 studies, 2503 women; random
      effects, T(2) = 2.39, Chi(2) = 203.55, df = 14, (P < 0.00001), I(2) = 93%). Women
      who were upright were also less likely to have caesarean section (RR 0.71, 95% CI
      0.54 to 0.94; 14 studies, 2682 women) and less likely to have an epidural (RR
      0.81, 95% CI 0.66 to 0.99, nine studies, 2107 women; random-effects, T(2) = 0.02,
      I(2) = 61%). Babies of mothers who were upright were less likely to be admitted
      to the neonatal intensive care unit, however this was based on one trial (RR
      0.20, 95% CI 0.04 to 0.89, one study, 200 women). There were no significant
      differences between groups for other outcomes including duration of the second
      stage of labour, or other outcomes related to the well being of mothers and
      babies.For Comparison 2: Upright and ambulant positions versus recumbent
      positions and bed care (with epidural: all women), there were no significant
      differences between groups for outcomes including duration of the second stage of
      labour, or other outcomes related to the well being of mothers and babies.
      AUTHORS' CONCLUSIONS: There is clear and important evidence that walking and
      upright positions in the first stage of labour reduces the duration of labour,
      the risk of caesarean birth, the need for epidural, and does not seem to be
      associated with increased intervention or negative effects on mothers' and
      babies' well being. Given the great heterogeneity and high performance bias of
      study situations, better quality trials are still required to confirm with any
      confidence the true risks and benefits of upright and mobile positions compared
      with recumbent positions for all women. Based on the current findings, we
      recommend that women in low-risk labour should be informed of the benefits of
      upright positions, and encouraged and assisted to assume whatever positions they
      choose.

PMID- 24105445
TI  - Molecular characterization of cancer reveals interactions between ionizing
      radiation and chemicals on rat mammary carcinogenesis.
AB  - Although various mechanisms have been inferred for combinatorial actions of
      multiple carcinogens, these mechanisms have not been well demonstrated in
      experimental carcinogenesis models. We evaluated mammary carcinogenesis initiated
      by combined exposure to various doses of radiation and chemical carcinogens.
      Female rats at 7 weeks of age were gamma-irradiated (0.2-2 Gy) and/or exposed to
      1-methyl-1-nitrosourea (MNU) (20 or 40 mg/kg, single intraperitoneal injection)
      or 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP) (40 mg/kg/day by gavage
      for 10 days) and were observed until 50 weeks of age. The incidence of mammary
      carcinoma increased steadily as a function of radiation dose in the absence of
      chemicals; mathematical analysis supported an additive increase when radiation
      was combined with a chemical carcinogen, irrespective of the chemical species and
      its dose. Hras mutations were characteristic of carcinomas that developed after
      chemical carcinogen treatments and were overrepresented in carcinomas induced by
      the combination of radiation and MNU (but not PhIP), indicating an interaction of
      radiation and MNU at the level of initiation. The expression profiles of seven
      classifier genes, previously shown to distinguish two classes of rat mammary
      carcinomas, categorized almost all examined carcinomas that developed after
      individual or combined treatments with radiation (1 Gy) and chemicals as
      belonging to a single class; more comprehensive screening using microarrays and a
      separate test sample set failed to identify differences in gene expression
      profiles among these carcinomas. These results suggest that a complex, multilevel
      interaction underlies the combinatorial action of radiation and chemical
      carcinogens in the experimental model. 

PMID- 24105446
TI  - Seven-year follow-up study of symptoms in asylum seekers and refugees with PTSD
      treated with trauma-focused groups.
AB  - OBJECTIVE: To examine sustainability of symptom outcomes of a 1-year phase-based
      trauma-focused, multimodal, and multicomponent group therapy in a day treatment
      program for posttraumatic stress disorder (PTSD) over an average period of 7
      years. METHOD: Iranian and Afghan patients (N = 69) were assessed with self-rated
      symptom checklists for PTSD, anxiety, and depression symptoms before (T1), after
      (T2), and up to 11 years upon completion of the treatment (T3). A series of mixed
      model regression analyses was applied to determine the course of the measured
      symptoms over time. RESULTS: At T2, all symptoms were reduced, but PTSD symptoms
      showed the strongest reduction. The trend of symptom reduction continued up to 5
      years posttreatment and was similar for all the examined symptoms. After 5 years,
      all symptoms started to worsen, but remained under baseline levels at T3.
      CONCLUSIONS: The applied treatment appears to improve mental health of the
      studied sample on both the short and longer term.

PMID- 24105447
TI  - Reduced-fat bologna sausages with improved lipid fraction.
AB  - BACKGROUND: This applied research was done in order to obtain cooked products
      (bologna sausages) with significantly lower amounts of energy, total fat and
      saturated fat and higher amounts of omega-3 fatty acids than conventional ones.
      Two subsequent experiments were performed. RESULTS: Experiment 1 aimed at pork
      back-fat reduction and enabled sausages to be obtained with 84 g kg-1 fat and
      1334 kcal kg-1, without significant negative effects on sensory quality.
      Carrageenan was used as fat replacer. Experiment 2 aimed at improving the lipid
      profile of the 'energy-reduced' sausages previously developed, by a partial
      substitution of the pork back-fat with a linseed oil-in water emulsion
      (substitution levels: 25-100%). Using the 100% substitution level gave rise to
      products with 27 g kg-1 alpha-linolenic acid, and low saturated fat content (13.5
      g kg-1), showing good sensory results regarding taste, smell and texture. The use
      of antioxidant maintained low TBARs (thiobarbituric acid reactive substances)
      values in all formulations. CONCLUSION: It is possible to obtain cooked meat
      products (bologna sausages) with low energy, low saturated fat and a high amount
      of omega-3 fatty acids simultaneously, applying a combination of the use of
      carrageenan, linseed oil emulsion and increment of water, without significant
      effects on sensory quality. Functional products, interesting from a nutritional
      standpoint, were achieved.

PMID- 24105448
TI  - Predicted cancer risks induced by computed tomography examinations during
      childhood, by a quantitative risk assessment approach.
AB  - The potential adverse effects associated with exposure to ionizing radiation from
      computed tomography (CT) in pediatrics must be characterized in relation to their
      expected clinical benefits. Additional epidemiological data are, however, still
      awaited for providing a lifelong overview of potential cancer risks. This paper
      gives predictions of potential lifetime risks of cancer incidence that would be
      induced by CT examinations during childhood in French routine practices in
      pediatrics. Organ doses were estimated from standard radiological protocols in 15
      hospitals. Excess risks of leukemia, brain/central nervous system, breast and
      thyroid cancers were predicted from dose-response models estimated in the
      Japanese atomic bomb survivors' dataset and studies of medical exposures.
      Uncertainty in predictions was quantified using Monte Carlo simulations. This
      approach predicts that 100,000 skull/brain scans in 5-year-old children would
      result in eight (90 % uncertainty interval (UI) 1-55) brain/CNS cancers and four
      (90 % UI 1-14) cases of leukemia and that 100,000 chest scans would lead to 31
      (90 % UI 9-101) thyroid cancers, 55 (90 % UI 20-158) breast cancers, and one (90
      % UI <0.1-4) leukemia case (all in excess of risks without exposure). Compared to
      background risks, radiation-induced risks would be low for individuals throughout
      life, but relative risks would be highest in the first decades of life.
      Heterogeneity in the radiological protocols across the hospitals implies that 5
      10 % of CT examinations would be related to risks 1.4-3.6 times higher than those
      for the median doses. Overall excess relative risks in exposed populations would
      be 1-10 % depending on the site of cancer and the duration of follow-up. The
      results emphasize the potential risks of cancer specifically from standard CT
      examinations in pediatrics and underline the necessity of optimization of
      radiological protocols.

PMID- 24105449
TI  - Proteomics in radiation research: present status and future perspectives.
AB  - Rapidly developing postgenome research has made proteins an attractive target for
      biological analysis. The well-established term of proteome is defined as the
      complete set of proteins expressed in a given cell, tissue or organism. Unlike
      the genome, a proteome is rapidly changing as it tends to adapt to
      microenvironmental signals. The systematic analysis of the proteome at a given
      time and state is referred to as proteomics. This technique provides information
      on the molecular and cellular mechanisms that regulate physiology and
      pathophysiology of the cell. Applications of proteome profiling in radiation
      research are increasing. However, the large-scale proteomics data sets generated
      need to be integrated into other fields of radiation biology to facilitate the
      interpretation of radiation-induced cellular and tissue effects. The aim of this
      review is to introduce the most recent developments in the field of radiation
      proteomics. 

PMID- 24105450
TI  - Prevention of hemolysis-induced organ damage by nutritional activation of the
      vagal anti-inflammatory reflex*.
AB  - OBJECTIVES: Acute hemolysis is associated with organ damage, inflammation, and
      impaired vascular function. Stimulation of the cholecystokinin-1 receptor
      dependent vagal anti-inflammatory reflex with lipid-rich enteral nutrition was
      demonstrated to prevent tissue damage and attenuate inflammation. This study
      investigates the effects of nutritional activation of the vagal anti-inflammatory
      reflex on organ integrity, systemic inflammation, and microcirculation during
      hemolysis. DESIGN: Prospective randomized controlled study. SETTING: University
      research unit. SUBJECTS: Male Sprague-Dawley rats. INTERVENTIONS: Intravascular
      hemolysis was simulated by infusion of prelysed erythrocytes. Animals were fasted
      or received lipid-rich enteral nutrition. Pegylated (PEG)-CCK9A, A70104 (a
      cholecystokinin-1 receptor antagonist), and chlorisondamine (a nicotinic
      acetylcholine receptor antagonist) were applied to investigate involvement of the
      vagal reflex. MEASUREMENTS AND MAIN RESULTS: Nutritional intervention reduced
      hemolysis-related renal tubular cell damage, hepatocyte damage, ileal leakage of
      horseradish peroxidase, and bacterial translocation compared with food
      deprivation (all p < 0.05). Also circulating interleukin (IL)-6 levels were
      decreased by enteral nutrition (p < 0.05). Blockage of the cholecystokinin-1
      receptor or the nicotinic acetylcholine receptor reversed the protective
      nutritional effects compared with vehicle (p < 0.05), whereas PEG-CCK9 mimicked
      the impact of enteral feeding in fasted animals (p < 0.05). Furthermore,
      nutritional intervention increased renal, hepatic, and intestinal blood flow
      compared with fasting (all p < 0.05), as evaluated using fluorescent
      microspheres. CONCLUSIONS: Nutritional activation of the vagal anti-inflammatory
      reflex preserves tissue integrity and attenuates systemic inflammation in a
      rodent model of acute hemolysis. In addition, lipid-rich nutrition improves
      renal, hepatic, and intestinal microcirculation. These findings implicate
      stimulation of the autonomic nervous system by nutritional means as a potential
      therapy to prevent complications of acute hemolysis. (Crit Care Med 2013; 41:e361
      e367).

PMID- 24105452
TI  - Multidisciplinary team training to enhance family communication in the ICU.
AB  - OBJECTIVES: Current guidelines from the U.S. Society for Critical Care Medicine
      state that training in "good communication skills...should become a standard
      component of medical education and ... available for all ICU caregivers". We
      sought to train multidisciplinary teams of ICU caregivers in communicating with
      the families of critically ill patients to improve staff confidence in
      communicating with families, as well as family satisfaction with their
      experiences in the ICU. DESIGN: Pre- and postintervention design. SETTING:
      Community hospital medical and surgical ICUs. PATIENTS: All patients admitted to
      ICU during the two time periods. INTERVENTION: Ninety-eight caregivers in
      multidisciplinary teams of five to eight individuals trained in a standardized
      approach to communicating with families of ICU patients using the Setup,
      Perception, Invitation, Knowledge, Emotions, Strategy (or Subsequent) (SPIKES)
      protocol followed by participation in a simulated family conference.
      MEASUREMENTS: Staff confidence in communicating with family members of critically
      ill patients was measured immediately before and 6-8 weeks after training
      sessions using a validated tool. Family satisfaction using seven items measuring
      effectiveness of communication from the Family Satisfaction in the ICU (24) tool
      in surveys received from family members of 121 patients admitted to the ICU
      before and 121 patients admitted to the ICU after trainings was completed. MAIN
      RESULTS: Using 46 matched pre- and postsurveys, staff confidence in communicating
      with family members of critically ill patients increased significantly (p <
      0.001) in each of 21 separate measures. Family satisfaction with communication
      showed significant (p < 0.05 or better) improvement in three of seven individual
      items compared with those same items pretraining. There was no decline in any
      individual item. CONCLUSIONS: A simple intervention resulted in improvement in
      staff confidence, as well as in multiple measures of family satisfaction with
      communication. This intervention is easily reproduced.

PMID- 24105451
TI  - Orexinergic activity modulates altered vital signs and pituitary hormone
      secretion in experimental sepsis.
AB  - OBJECTIVES: Sepsis is a common, lethal poorly understood disorder affecting
      nearly a million Americans annually. The syndrome is characterized by altered
      cardiodynamics, respiration, metabolism, pituitary function, arousal, and
      impaired interaction among organ systems. The immunologic and endocrine systems,
      which are in part responsible for organ-organ communication, have been studied
      extensively in sepsis. However, little is known about sepsis-induced changes in
      central nervous system activity. HYPOTHESIS: A defect in hypothalamic neurons
      secreting the neurotransmitter orexin modulates physiologic derangements in
      sepsis. DESIGN: Animal study. SETTING: University Research Laboratory.
      INTERVENTIONS: Male C57Bl6 mice were made septic using cecal ligation and
      puncture. Data were collected 24 or 48 hours later, blood was collected, animals
      were killed, and brain tissue was harvested, fixed, and sectioned. Hypothalamic
      sections were subjected to immunohistochemistry using antibodies to orexin and c
      Fos, a marker of neuronal activity. In a separate cohort of mice, cannulas were
      placed in the right lateral cerebral ventricle. Cecal ligation and puncture was
      performed 1 week later. At 24 or 48 hours post-cecal ligation and puncture, vital
      signs were measured, and1 uL of saline with or without 3 nmol orexin-A was
      infused. Vital signs were repeated at 25 or 49 hours post-cecal ligation and
      puncture, blood was collected, animals were killed, and brains were removed,
      fixed, sectioned, and stained. MEASUREMENTS AND MAIN RESULTS: Orexinergic
      activity decreased six-fold following cecal ligation and puncture. This change
      was associated with decreases in arousal, temperature, and heart and respiratory
      rates. Levels of selected pituitary hormones increased 24 hours post-cecal
      ligation and puncture but were significantly lower than baseline at 48 hours.
      Injection of orexin-A increased vital signs to baseline levels. Hormone levels
      were unaffected at 25 hours but increased to supranormal levels at 49 hours.
      CONCLUSIONS: Sepsis-induced changes in activity, vital signs, and pituitary
      hormones are modulated by the orexinergic system. This finding implicates central
      nervous system dysfunction in the pathogenesis of sepsis, suggesting further
      study of neurological dysfunction to identify novel approaches to management.

PMID- 24105453
TI  - Feasibility and perceived benefits of a framework for physician-parent follow-up
      meetings after a child's death in the PICU.
AB  - OBJECTIVE: To evaluate the feasibility and perceived benefits of conducting
      physician-parent follow-up meetings after a child's death in the PICU according
      to a framework developed by the Collaborative Pediatric Critical Care Research
      Network. DESIGN: Prospective observational study. SETTING: Seven Collaborative
      Pediatric Critical Care Research Network-affiliated children's hospitals.
      SUBJECTS: Critical care attending physicians, bereaved parents, and meeting
      guests (i.e., parent support persons, other health professionals). INTERVENTIONS:
      Physician-parent follow-up meetings using the Collaborative Pediatric Critical
      Care Research Network framework. MEASUREMENTS AND MAIN RESULTS: Forty-six
      critical care physicians were trained to conduct follow-up meetings using the
      framework. All meetings were video recorded. Videos were evaluated for the
      presence or absence of physician behaviors consistent with the framework. Present
      behaviors were evaluated for performance quality using a 5-point scale (1 = low,
      5 = high). Participants completed meeting evaluation surveys. Parents of 194
      deceased children were mailed an invitation to a follow-up meeting. Of these, one
      or both parents from 39 families (20%) agreed to participate, 80 (41%) refused,
      and 75 (39%) could not be contacted. Of 39 who initially agreed, three meetings
      were canceled due to conflicting schedules. Thirty-six meetings were conducted
      including 54 bereaved parents, 17 parent support persons, 23 critical care
      physicians, and 47 other health professionals. Physician adherence to the
      framework was high; 79% of behaviors consistent with the framework were rated as
      present with a quality score of 4.3 +/- 0.2. Of 50 evaluation surveys completed
      by parents, 46 (92%) agreed or strongly agreed the meeting was helpful to them
      and 40 (89%) to others they brought with them. Of 36 evaluation surveys completed
      by critical care physicians (i.e., one per meeting), 33 (92%) agreed or strongly
      agreed the meeting was beneficial to parents and 31 (89%) to them. CONCLUSIONS:
      Follow-up meetings using the Collaborative Pediatric Critical Care Research
      Network framework are feasible and viewed as beneficial by meeting participants.
      Future research should evaluate the effects of follow-up meetings on bereaved
      parents' health outcomes.

PMID- 24105454
TI  - Percutaneous coronary intervention for nonculprit vessels in cardiogenic shock
      complicating ST-segment elevation acute myocardial infarction.
AB  - OBJECTIVES: We investigated the clinical impact of multivessel percutaneous
      coronary intervention in ST-segment elevation myocardial infarction complicated
      by cardiogenic shock with multivessel disease. DESIGN: A prospective,
      multicenter, observational study. SETTING: Cardiac ICU of a university hospital.
      PATIENTS: Between November 2005 and September 2010, 338 patients were selected.
      Inclusion criteria were as follows: 1) ST-segment elevation myocardial infarction
      with cardiogenic shock and 2) multivessel disease with successful primary
      percutaneous coronary intervention for the infarct-related artery. Patients were
      divided into multivessel percutaneous coronary intervention and culprit-only
      percutaneous coronary intervention. INTERVENTIONS: None. MEASUREMENTS AND MAIN
      RESULTS: Primary outcome was all-cause mortality. Median follow-up duration was
      224 days (interquartile range, 46-383 d). Multivessel percutaneous coronary
      intervention was performed during the primary percutaneous coronary intervention
      in 60 patients (17.8%). In-hospital mortality was similar in both groups
      (multivessel percutaneous coronary intervention vs culprit-only percutaneous
      coronary intervention, 31.7% vs 24.5%; p = 0.247). All-cause mortality during
      follow-up was not significantly different between the two groups after adjusting
      for patient, angiographic, and procedural characteristics as well as propensity
      scores for receiving multivessel percutaneous coronary intervention (35.0% vs
      30.6%; adjusted hazard ratio, 1.06; 95% CI, 0.61-1.86; p = 0.831). There were no
      significant differences between the groups in rates of major adverse cardiac
      events (41.7% vs 37.1%; adjusted hazard ratio, 1.03; 95% CI, 0.62-1.71; p =
      0.908) and any revascularization (6.7% vs 4.7%; adjusted hazard ratio, 1.88; 95%
      CI, 0.51-6.89; p = 0.344). CONCLUSIONS: Multivessel percutaneous coronary
      intervention could not reduce the prevalence of mortality in patients with
      cardiogenic shock complicating ST-segment elevation myocardial infarction and
      multivessel disease during primary percutaneous coronary intervention.

PMID- 24105455
TI  - Adjuvant treatment with a mammalian target of rapamycin inhibitor, sirolimus, and
      steroids improves outcomes in patients with severe H1N1 pneumonia and acute
      respiratory failure.
AB  - OBJECTIVES: Severe H1N1 pneumonia with acute respiratory failure results in
      infiltration of lungs due to the presence of hyperactive immune cells. Rapamycin
      and corticosteroids inhibit this immune response by blocking the activation of T
      and B cells. DESIGN: Open-label prospective randomized controlled trial. SETTING:
      A tertiary medical center, Chang Gung Memorial Hospital, located in Taiwan.
      PATIENTS: Between 2009 and 2011, of 4,012 H1N1-infected patients, 38 patients
      with severe H1N1 pneumonia and acute respiratory failure were enrolled.
      MEASUREMENTS AND MAIN RESULTS: Thirty-eight patients with confirmed H1N1
      pneumonia and on mechanical ventilatory support were randomized to receive
      adjuvant treatment of corticosteroids with an mTOR inhibitor, either with
      sirolimus (Rapamune 2 mg/d) (sirolimus group, n = 19) for 14 days or without
      sirolimus (nonsirolimus group, n = 19). The clinical values measured included
      PaO2/FIO2, Sequential Organ Failure Assessment score, duration of ventilatory
      support, and mortality. The baseline demography was similar between the two
      groups. After treatment, the PaO2/FIO2 values on day 3 (167.5 [95% CI, 86.7-209.2
      mm Hg], n = 19 vs 106.8 [95% CI, 73.0-140.7 mm Hg], n = 19; p = 0.025] and day 7
      (241.6 [95% CI, 185.2-297.9 mm Hg], n = 19 vs 147.0 [95% CI, 100.7-193.7 mm Hg],
      n = 17; p = 0.008) in the sirolimus group were significantly better over the
      nonsirolimus group. Similarly, the Sequential Organ Failure Assessment score on
      day 3 (4.3 [95% CI, 3.1-5.5]; p = 0.029) and day 7 (5.9 [95% CI, 4.8-6.9], n = 19
      and 6.2 [95% CI, 4.7-7.8], n = 17, respectively) significantly improved in the
      sirolimus group. The liberation from a mechanical ventilator at 3 months was also
      better in the sirolimus combined with corticosteroids treatment. Similarly, the
      duration of ventilator use was significantly shorter in the sirolimus group
      (median, 7 vs 15 d; p = 0.03 by log-rank test). In the sirolimus combined with
      corticosteroids treatment group, a rapid clearance of virus also occurred after 7
      days of treatment. CONCLUSIONS: In patients with severe H1N1 pneumonia, early
      adjuvant treatment with corticosteroids and an mTOR inhibitor was associated with
      improvement in outcomes, such as hypoxia, multiple organ dysfunction, virus
      clearance, and shortened liberation of ventilator and ventilator days.

PMID- 24105456
TI  - Effect of oropharyngeal povidone-iodine preventive oral care on ventilator
      associated pneumonia in severely brain-injured or cerebral hemorrhage patients: a
      multicenter, randomized controlled trial.
AB  - OBJECTIVE: To evaluate the efficacy and safety of oral care with povidone-iodine
      on the occurrence of ventilator-associated pneumonia in a high-risk population.
      DESIGN: A multicenter, placebo-controlled, randomized, double-blind, two-parallel
      group trial performed between May 2008 and May 2011. SETTING: Six ICUs in France.
      PATIENTS: One hundred seventy-nine severely brain-injured patients (Glasgow Coma
      Scale <= 8) or cerebral hemorrhage expected to be mechanically ventilated for
      more than 24 hours. INTERVENTIONS: Participants were randomly assigned to receive
      oropharyngeal care with povidone-iodine (n = 91) or placebo (n = 88) six times
      daily until mechanical ventilation withdrawal. MEASUREMENTS AND MAIN RESULTS:
      Primary endpoint was the rate of ventilator-associated pneumonia. Secondary
      endpoint included the rates of ventilator-associated tracheobronchitis and acute
      respiratory distress syndrome and patient's outcome. The number of patients
      evaluable for the primary endpoint (preplanned modified intention-to-treat
      population) was 150 (78 in the povidone-iodine group, 72 in the placebo group).
      Ventilator-associated pneumonia occurred in 24 patients (31%) in the povidone
      iodine group and 20 (28%) in the placebo group (relative risk, 1.11 [95% CI, 0.67
      1.82]; p = 0.69). There was no significant difference between the two groups for
      ventilator-associated tracheobronchitis: eight patients (10%) in the povidone
      iodine group and five patients (7%) in the placebo group (relative risk, 1.48
      [95% CI, 0.51-4.31]; p = 0.47). Acute respiratory distress syndrome occurred in
      five patients in the povidone-iodine group but not in the placebo group (p =
      0.06). There was no difference between groups for ICU and hospital lengths of
      stay, as well as ICU and 90-day mortality. CONCLUSIONS: There is no evidence to
      recommend oral care with povidone-iodine to prevent ventilator-associated
      pneumonia in high-risk patients. Furthermore, this strategy seems to increase the
      rate of acute respiratory distress syndrome.

PMID- 24105458
TI  - Silica supported Fe(3)O(4) magnetic nanoparticles for magnetic solid-phase
      extraction and magnetic in-tube solid-phase microextraction: application to
      organophosphorous compounds.
AB  - This work demonstrates the application of silica supported Fe3O4 nanoparticles as
      sorbent phase for magnetic solid-phase extraction (MSPE) and magnetic on-line in
      tube solid-phase microextraction (Magnetic-IT-SPME) combined with capillary
      liquid chromatography-diode array detection (CapLC-DAD) to determine
      organophosphorous compounds (OPs) at trace level. In MSPE, magnetism is used as
      separation tool while in Magnetic-IT-SPME, the application of an external
      magnetic field gave rise to a significant improvement of the adsorption of OPs on
      the sorbent phase. Extraction efficiency, analysis time, reproducibility and
      sensitivity have been compared. This work showed that Magnetic-IT-SPME can be
      extended to OPs with successful results in terms of simplicity, speed, extraction
      efficiency and limit of detection. Finally, wastewater samples were analysed to
      determine OPs at nanograms per litre. 

PMID- 24105457
TI  - Isomorphic red blood cells using automated urine flow cytometry is a reliable
      method in diagnosis of bladder cancer.
AB  - BACKGROUND: We aimed to identify patients with a chief complaint of hematuria who
      could safely avoid unnecessary radiation and instrumentation in the diagnosis of
      bladder cancer (BC), using automated urine flow cytometry to detect isomorphic
      red blood cells (RBCs) in urine. METHODS: We acquired urine samples from 134
      patients over the age of 35 years with a chief complaint of hematuria and a
      positive urine occult blood test or microhematuria. The data were analyzed using
      the UF-1000i ((r)) (Sysmex Co., Ltd., Kobe, Japan) automated urine flow cytometer
      to determine RBC morphology, which was classified as isomorphic or dysmorphic.
      The patients were divided into two groups (BC versus non-BC) for statistical
      analysis. Multivariate logistic regression analysis was used to determine the
      predictive value of flow cytometry versus urine cytology, the bladder tumor
      antigen test, occult blood in urine test, and microhematuria test. RESULTS: BC
      was confirmed in 26 of 134 patients (19.4 %). The area under the curve for RBC
      count using the automated urine flow cytometer was 0.94, representing the highest
      reference value obtained in this study. Isomorphic RBCs were detected in all
      patients in the BC group. On multivariate logistic regression analysis, only
      isomorphic RBC morphology was significantly predictive for BC (p < 0.001).
      Analytical parameters such as sensitivity, specificity, positive predictive
      value, and negative predictive value of isomorphic RBCs in urine were 100.0,
      91.7, 74.3, and 100.0 %, respectively. CONCLUSION: Detection of urinary
      isomorphic RBCs using automated urine flow cytometry is a reliable method in the
      diagnosis of BC with hematuria.

PMID- 24105460
TI  - Modeling guidance and recognition in categorical search: bridging human and
      computer object detection.
AB  - Search is commonly described as a repeating cycle of guidance to target-like
      objects, followed by the recognition of these objects as targets or distractors.
      Are these indeed separate processes using different visual features? We addressed
      this question by comparing observer behavior to that of support vector machine
      (SVM) models trained on guidance and recognition tasks. Observers searched for a
      categorically defined teddy bear target in four-object arrays. Target-absent
      trials consisted of random category distractors rated in their visual similarity
      to teddy bears. Guidance, quantified as first-fixated objects during search, was
      strongest for targets, followed by target-similar, medium-similarity, and target
      dissimilar distractors. False positive errors to first-fixated distractors also
      decreased with increasing dissimilarity to the target category. To model
      guidance, nine teddy bear detectors, using features ranging in biological
      plausibility, were trained on unblurred bears then tested on blurred versions of
      the same objects appearing in each search display. Guidance estimates were based
      on target probabilities obtained from these detectors. To model recognition, nine
      bear/nonbear classifiers, trained and tested on unblurred objects, were used to
      classify the object that would be fixated first (based on the detector estimates)
      as a teddy bear or a distractor. Patterns of categorical guidance and recognition
      accuracy were modeled almost perfectly by an HMAX model in combination with a
      color histogram feature. We conclude that guidance and recognition in the context
      of search are not separate processes mediated by different features, and that
      what the literature knows as guidance is really recognition performed on blurred
      objects viewed in the visual periphery. 

PMID- 24105461
TI  - A novel homozygous mutation in G6PC3 presenting as cyclic neutropenia and severe
      congenital neutropenia in the same family.
AB  - PURPOSE: Patients with autosomal recessive cyclic neutropenia have no known
      causative genetic defect yet. METHODS: Autozygosity mapping on two branches of an
      extended multiplex consanguineous family presenting with cyclic neutropenia or
      severe congenital neutropenia to look for candidate gene, followed by candidate
      gene selection and sequencing. RESULTS: A single autozygous interval on
      Chr17:33,901,938-45,675,414 that is exclusively shared by the affected members
      was identified. This interval spans 11.8 Mb and contains 30 genes. Review of
      these genes highlighted G6PC3 as the most likely candidate given its known role
      in neutrophil biology. Direct sequencing revealed a novel homozygous mutation
      (NM_138387.3, c.974T > G, p.Leu325Arg). Two of our patients had associated
      congenital defects that are known to occur in patients with G6PC3 mutations,
      including congenital heart disease and intermittent thrombocytopenia. CONCLUSION:
      Biallelic G6PC3 defects should be considered in patients with autosomal recessive
      cyclic neutropenia, especially those with typical associated congenital defects.

PMID- 24105462
TI  - A 1-year-old girl with a gain-of-function STAT1 mutation treated with
      hematopoietic stem cell transplantation.

PMID- 24105463
TI  - Thy1+ Sca1+ innate lymphoid cells infiltrate the CNS during autoimmune
      inflammation, but do not contribute to disease development.
AB  - IL-23 is absolutely crucial for the development of T-cell driven autoimmune
      disease in mice. Even though IL-23 is widely held to be involved in the
      stabilization of IL-17-secreting T cells, naive T cells lack the IL-23 receptor.
      Thus, the primary cellular target of IL-23 in the context of autoimmunity is a
      subject of some debate. Innate lymphoid cells (ILCs) are a recently discovered
      family of lymphocytes being involved in early host defense, particularly at
      mucosal epithelial surfaces. Given the fact that RORgammat-dependent ILCs (group
      3 ILCs) constitutively express the IL-23-receptor, and that they have been
      implicated in intestinal autoimmunity, we hypothesized that ILCs could contribute
      to the early development of autoimmune neuroinflammation. Through systematic
      analysis, we detected a sizable population of Thy1(+) Sca1(+) ILCs in the
      inflamed CNS tissue. CNS-infiltrating ILCs were characterized by expression of
      the IL-7-receptor and production of proinflammatory IL-17 and IFN-gamma.
      Furthermore, genetic fate-mapping revealed their dependence on the transcription
      factor RORgammat. However, upon specific in vivo ablation of this cell
      population, we found that they do not influence the course of the disease. 

PMID- 24105464
TI  - TDP-43 Phosphorylation by casein kinase Iepsilon promotes oligomerization and
      enhances toxicity in vivo.
AB  - Dominant mutations in transactive response DNA-binding protein-43 (TDP-43) cause
      amyotrophic lateral sclerosis. TDP-43 inclusions occur in neurons, glia and
      muscle in this disease and in sporadic and inherited forms of frontotemporal
      lobar degeneration. Cytoplasmic localization, cleavage, aggregation and
      phosphorylation of TDP-43 at the Ser409/410 epitope have been associated with
      disease pathogenesis. TDP-43 aggregation is not a common feature of mouse models
      of TDP-43 proteinopathy, and TDP-43 is generally not thought to acquire an
      amyloid conformation or form fibrils. A number of putative TDP-43 kinases have
      been identified, but whether any of these functions to regulate TDP-43
      phosphorylation or toxicity in vivo is not known. Here, we demonstrate that human
      TDP-43(Q331K) undergoes cytoplasmic localization and aggregates when misexpressed
      in Drosophila when compared with wild-type and M337V forms. Coexpression of Q331K
      with doubletime (DBT), the fly homolog of casein kinase Iepsilon (CKIepsilon),
      enhances toxicity. There is at best modest basal phosphorylation of misexpressed
      human TDP-43 in Drosophila, but coexpression with DBT increases Ser409/410
      phosphorylation of all TDP-43 isoforms tested. Phosphorylation of TDP-43 in the
      fly is specific for DBT, as it is not observed using the validated tau kinases
      GSK-3beta, PAR-1/MARK2 or CDK5. Coexpression of DBT with TDP-43(Q331K) enhances
      the formation of high-molecular weight oligomeric species coincident with
      enhanced toxicity, and treatment of recombinant oligomeric TDP-43 with rat CKI
      strongly enhances its toxicity in mammalian cell culture. These data identify
      CKIepsilon as a potent TDP-43 kinase in vivo and implicate oligomeric species as
      the toxic entities in TDP-43 proteinopathies. 

PMID- 24105465
TI  - RNA sequencing-based identification of aberrant imprinting in cloned mice.
AB  - Animals cloned by somatic cell nuclear transfer (SCNT) provide a unique model for
      understanding the mechanisms of nuclear epigenetic reprogramming to a state of
      totipotency. Though many phenotypic abnormalities have been demonstrated in
      cloned animals, the underlying mechanisms are not well understood. In this study,
      we performed transcriptome-wide allelic expression analyses in brain and
      placental tissues of cloned mice. We found that Gab1, Sfmbt2 and Slc38a4 showed
      loss of imprinting in all cloned mice analyzed, which might be involved in
      placentomegaly of cloned mice. These three genes did not require de novo DNA
      methylation in growing oocytes for the establishment of imprinting, implying the
      involvement of a de novo DNA methylation-independent mechanism. Loss of Dlk1-Dio3
      imprinting was also observed in nearly half of cloned mouse embryos and showed a
      strong correlation with embryonic lethality. Our findings are essential to
      understand the underlying mechanisms of developmental abnormalities of cloned
      animals. We also emphasize that particular attention should be paid to specific
      imprinted genes for therapeutic and agricultural applications of SCNT.

PMID- 24105466
TI  - MeCP2: a novel Huntingtin interactor.
AB  - Transcriptional dysregulation has been proposed to play a major role in the
      pathology of Huntington's disease (HD). However, the mechanisms that cause
      selective downregulation of target genes remain unknown. Previous studies have
      shown that mutant huntingtin (Htt) protein interacts with a number of
      transcription factors thereby altering transcription. Here we report that Htt
      directly interacts with methyl-CpG binding protein 2 (MeCP2) in mouse and
      cellular models of HD using complimentary biochemical and Fluorescent Lifetime
      Imaging to measure Forster Resonance Energy Transfer approaches. Htt-MeCP2
      interactions are enhanced in the presence of the expanded polyglutamine (polyQ)
      tract and are stronger in the nucleus compared with the cytoplasm. Furthermore,
      we find increased binding of MeCP2 to the promoter of brain-derived neurotrophic
      factor (BDNF), a gene that is downregulated in HD, in the presence of mutant Htt.
      Finally, decreasing MeCP2 levels in mutant Htt-expressing cells using siRNA
      increases BDNF levels, suggesting that MeCP2 downregulates BDNF expression in HD.
      Taken together, these findings suggest that aberrant interactions between Htt and
      MeCP2 contribute to transcriptional dysregulation in HD. 

PMID- 24105467
TI  - Presenilin influences glycogen synthase kinase-3 beta (GSK-3beta) for kinesin-1
      and dynein function during axonal transport.
AB  - Within axons, molecular motors transport essential components required for
      neuronal growth and viability. Although many levels of control and regulation
      must exist for proper anterograde and retrograde transport of vital proteins,
      little is known about these mechanisms. We previously showed that presenilin
      (PS), a gene involved in Alzheimer's disease (AD), influences kinesin-1 and
      dynein function in vivo. Here, we show that these PS-mediated effects on motor
      protein function are via a pathway that involves glycogen synthase kinase-3beta
      (GSK-3beta). PS genetically interacts with GSK-3beta in an activity-dependent
      manner. Excess of active GSK-3beta perturbed axonal transport by causing axonal
      blockages, which were enhanced by reduction of kinesin-1 or dynein. These GSK
      3beta-mediated axonal defects do not appear to be caused by disruptions or
      alterations in microtubules (MTs). Excess of non-functional GSK-3beta did not
      affect axonal transport. Strikingly, GSK-3beta-activity-dependent axonal
      transport defects were enhanced by reduction of PS. Collectively, our findings
      suggest that PS and GSK-3beta are required for normal motor protein function. Our
      observations propose a model, in which PS likely plays a role in regulating GSK
      3beta activity during transport. These findings have important implications for
      our understanding of the complex regulatory machinery that must exist in vivo and
      how this system is coordinated during the motility of vesicles within axons. 

PMID- 24105468
TI  - Parkin overexpression ameliorates hippocampal long-term potentiation and beta
      amyloid load in an Alzheimer's disease mouse model.
AB  - Alzheimer's disease (AD) is a progressive neurodegenerative disorder
      characterized by a severe decline of memory performance. A widely studied AD
      mouse model is the APPswe/PSEN1DeltaE9 (APP/PS1) strain, as mice exhibit amyloid
      plaques as well as impaired memory capacities. To test whether restoring synaptic
      plasticity and decreasing beta-amyloid load by Parkin could represent a potential
      therapeutic target for AD, we crossed APP/PS1 transgenic mice with transgenic
      mice overexpressing the ubiquitin ligase Parkin and analyzed offspring
      properties. Overexpression of Parkin in APP/PS1 transgenic mice restored activity
      dependent synaptic plasticity and rescued behavioral abnormalities. Moreover,
      overexpression of Parkin was associated with down-regulation of APP protein
      expression, decreased beta-amyloid load and reduced inflammation. Our data
      suggest that Parkin could be a promising target for AD therapy. 

PMID- 24105469
TI  - Recessive TTN truncating mutations define novel forms of core myopathy with heart
      disease.
AB  - Core myopathies (CM), the main non-dystrophic myopathies in childhood, remain
      genetically unexplained in many cases. Heart disease is not considered part of
      the typical CM spectrum. No congenital heart defect has been reported, and
      childhood-onset cardiomyopathy has been documented in only two CM families with
      homozygous mutations of the TTN gene. TTN encodes titin, a giant protein of
      striated muscles. Recently, heterozygous TTN truncating mutations have also been
      reported as a major cause of dominant dilated cardiomyopathy. However, relatively
      few TTN mutations and phenotypes are known, and titin pathophysiological role in
      cardiac and skeletal muscle conditions is incompletely understood. We analyzed a
      series of 23 families with congenital CM and primary heart disease using TTN M
      line-targeted sequencing followed in selected patients by whole-exome sequencing
      and functional studies. We identified seven novel homozygous or compound
      heterozygous TTN mutations (five in the M-line, five truncating) in 17% patients.
      Heterozygous parents were healthy. Phenotype analysis identified four novel
      titinopathies, including cardiac septal defects, left ventricular non-compaction,
      Emery-Dreifuss muscular dystrophy or arthrogryposis. Additionally, in vitro
      studies documented the first-reported absence of a functional titin kinase domain
      in humans, leading to a severe antenatal phenotype. We establish that CM are
      associated with a large range of heart conditions of which TTN mutations are a
      major cause, thereby expanding the TTN mutational and phenotypic spectrum.
      Additionally, our results suggest titin kinase implication in cardiac
      morphogenesis and demonstrate that heterozygous TTN truncating mutations may not
      manifest unless associated with a second mutation, reassessing the paradigm of
      their dominant expression. 

PMID- 24105471
TI  - Methylene blue rescues heart defects in a Drosophila model of Friedreich's
      ataxia.
AB  - Friedreich's ataxia (FRDA), the most common hereditary ataxia, is characterized
      by progressive degeneration of the central and peripheral nervous system,
      hypertrophic cardiomyopathy and a high risk of diabetes. FRDA is caused by
      abnormally low levels of frataxin, a highly conserved mitochondrial protein.
      Drosophila has been previously successfully used to model FRDA in various cell
      types, including neurons and glial cells. Here, we report the development of a
      Drosophila cardiac model of FRDA. In vivo heart imaging revealed profound
      impairments in heart function in frataxin-depleted Drosophila, including a strong
      increase in end-systolic and end-diastolic diameters and a decrease in fractional
      shortening (FS). These features, reminiscent of pathological phenotypes in
      humans, are fully rescued by complementation with human frataxin, suggesting
      conserved cardiac functions of frataxin between the two organisms. Oxidative
      stress is not a major factor of heart impairment in frataxin-depleted flies,
      suggesting the involvement of other pathological mechanisms notably mitochondrial
      respiratory chain (MRC) dysfunction. Accordingly, we report that methylene blue
      (MB), a compound known to act as an alternative electron carrier that bypasses
      mitochondrial complexes I-III, was able to prevent heart dysfunction. MB also
      partially rescued the phenotype when administered post-symptomatically. Analysis
      of MB derivatives demonstrates that only compounds with electron carrier
      properties are able to prevent the heart phenotype. Thus MB, a compound already
      used for several clinical applications, appears promising for the treatment of
      the heart dysfunctions that are a major cause of death of FRDA patients. This
      work provides the grounds for further evaluation of MB action in mammals. 

PMID- 24105470
TI  - A meta-analysis of genome-wide association studies for adiponectin levels in East
      Asians identifies a novel locus near WDR11-FGFR2.
AB  - Blood levels of adiponectin, an adipocyte-secreted protein correlated with
      metabolic and cardiovascular risks, are highly heritable. Genome-wide association
      (GWA) studies for adiponectin levels have identified 14 loci harboring variants
      associated with blood levels of adiponectin. To identify novel adiponectin
      associated loci, particularly those of importance in East Asians, we conducted a
      meta-analysis of GWA studies for adiponectin in 7827 individuals, followed by two
      stages of replications in 4298 and 5954 additional individuals. We identified a
      novel adiponectin-associated locus on chromosome 10 near WDR11-FGFR2 (P = 3.0 *
      10(-14)) and provided suggestive evidence for a locus on chromosome 12 near OR8S1
      LALBA (P = 1.2 * 10(-7)). Of the adiponectin-associated loci previously
      described, we confirmed the association at CDH13 (P = 6.8 * 10(-165)), ADIPOQ (P
      = 1.8 * 10(-22)), PEPD (P = 3.6 * 10(-12)), CMIP (P = 2.1 * 10(-10)), ZNF664 (P =
      2.3 * 10(-7)) and GPR109A (P = 7.4 * 10(-6)). Conditional analysis at ADIPOQ
      revealed a second signal with suggestive evidence of association only after
      conditioning on the lead SNP (Pinitial = 0.020; Pconditional = 7.0 * 10(-7)). We
      further confirmed the independence of two pairs of closely located loci (<2 Mb)
      on chromosome 16 at CMIP and CDH13, and on chromosome 12 at GPR109A and ZNF664.
      In addition, the newly identified signal near WDR11-FGFR2 exhibited evidence of
      association with triglycerides (P = 3.3 * 10(-4)), high density lipoprotein
      cholesterol (HDL-C, P = 4.9 * 10(-4)) and body mass index (BMI)-adjusted waist
      hip ratio (P = 9.8 * 10(-3)). These findings improve our knowledge of the genetic
      basis of adiponectin variation, demonstrate the shared allelic architecture for
      adiponectin with lipids and central obesity and motivate further studies of
      underlying mechanisms. 

PMID- 24105473
TI  - Methods to elicit probability distributions from experts: a systematic review of
      reported practice in health technology assessment.
AB  - BACKGROUND: Elicitation is a technique that can be used to obtain probability
      distribution from experts about unknown quantities. We conducted a methodology
      review of reports where probability distributions had been elicited from experts
      to be used in model-based health technology assessments. METHODS: Databases
      including MEDLINE, EMBASE and the CRD database were searched from inception to
      April 2013. Reference lists were checked and citation mapping was also used.
      Studies describing their approach to the elicitation of probability distributions
      were included. Data was abstracted on pre-defined aspects of the elicitation
      technique. Reports were critically appraised on their consideration of the
      validity, reliability and feasibility of the elicitation exercise. RESULTS:
      Fourteen articles were included. Across these studies, the most marked features
      were heterogeneity in elicitation approach and failure to report key aspects of
      the elicitation method. The most frequently used approaches to elicitation were
      the histogram technique and the bisection method. Only three papers explicitly
      considered the validity, reliability and feasibility of the elicitation
      exercises. CONCLUSION: Judged by the studies identified in the review, reports of
      expert elicitation are insufficient in detail and this impacts on the perceived
      usability of expert-elicited probability distributions. In this context, the
      wider credibility of elicitation will only be improved by better reporting and
      greater standardisation of approach. Until then, the advantage of eliciting
      probability distributions from experts may be lost.

PMID- 24105474
TI  - The diagnostic accuracy of two tense measures for identifying 3-year-olds with
      language impairment.
AB  - PURPOSE: The authors of this study investigated the diagnostic accuracy of the
      Finite Verb Morphology Composite (FVMC; Bedore & Leonard, 1998) and the Tense and
      Agreement Productivity Score (TAPS; Hadley & Short, 2005) in identifying 3-year
      olds with language impairment (LI). METHOD: Eighteen pairs of 3-year-olds with
      and without LI participated in the current study. The FVMC and the TAPS were
      computed from 100- and 50-utterance language samples. RESULTS: The FVMC and TAPS
      demonstrated higher diagnostic accuracy in the 100-utterance samples than in the
      50-utterance samples. For 100-utterance samples, when children's age or severity
      was not considered, the FVMC showed a slight advantage over the TAPS in
      diagnostic accuracy. However, when children's age or severity was considered, the
      opposite pattern was observed. CONCLUSION: Both the FVMC and TAPS can be used to
      differentiate 3-year-olds with and without LI. To reliably identify 3-year-olds
      with LI by using tense measures, language samples with at least 100 utterances
      are recommended.

PMID- 24105472
TI  - NLRP7 affects trophoblast lineage differentiation, binds to overexpressed YY1 and
      alters CpG methylation.
AB  - Maternal-effect mutations in NLRP7 cause rare biparentally inherited hydatidiform
      moles (BiHMs), abnormal pregnancies containing hypertrophic vesicular trophoblast
      but no embryo. BiHM trophoblasts display abnormal DNA methylation patterns
      affecting maternally methylated germline differentially methylated regions
      (gDMRs), suggesting that NLRP7 plays an important role in reprogramming imprinted
      gDMRs. How NLRP7-a component of the CATERPILLAR family of proteins involved in
      innate immunity and apoptosis-causes these specific DNA methylation and
      trophoblast defects is unknown. Because rodents lack NLRP7, we used human
      embryonic stem cells to study its function and demonstrate that NLRP7 interacts
      with YY1, an important chromatin-binding factor. Reduced NLRP7 levels alter DNA
      methylation and accelerate trophoblast lineage differentiation. NLRP7 thus
      appears to function in chromatin reprogramming and DNA methylation in the
      germline or early embryonic development, functions not previously associated with
      members of the NLRP family. 

PMID- 24105475
TI  - Retrospective cost-effectiveness analysis of treatments for aphasia: an approach
      using experimental data.
AB  - PURPOSE: Evidence supports the effectiveness of speech-language treatment for
      individuals with aphasia, yet less is known about the cost-effectiveness of such
      treatments. The purpose of this study was to examine the incremental cost and
      cost-effectiveness of aphasia treatment using previously published data. METHOD:
      The authors completed a retrospective cost-effectiveness analysis using
      experimental data that they extracted from 19 previously published aphasia
      treatment studies. Average and incremental cost-effectiveness ratios were
      calculated based on participants' pre- and posttreatment proficiency scores.
      RESULTS: The average cost-effectiveness ratio for all sessions was $9.54 for each
      1% increase in the outcome of interest. Measures of incremental cost
      effectiveness indicated that aphasia treatments resulted in statistically
      significant improvements up to and including 17 treatment sessions. Increases in
      proficiency occurred at a cost of approximately $7.00 per 1% increase for the
      first 3 sessions to more than $20.00 in the 14th session; the ratio was either
      not statistically significant or dominated (more costly and less effective) in
      later sessions. CONCLUSIONS: This cost-effectiveness analysis demonstrated that
      initial aphasia treatment sessions resulted in relatively larger and more cost
      effective benefits than did later aphasia treatment sessions. The findings
      reported here are preliminary and have limitations. Prospective studies are
      needed to examine the cost-effectiveness of speech-language treatment for
      individuals with aphasia.

PMID- 24105476
TI  - Sterol regulatory element-binding protein-1/fatty acid synthase involvement in
      proliferation inhibition and apoptosis promotion induced by progesterone in
      endometrial cancer.
AB  - BACKGROUND: The number of endometrial cancer (EC) cases is escalating rapidly,
      with no evident improvements in survival rates. The downregulation of
      progesterone receptor, resulting in progestin resistance, is presently a major
      problem regarding the therapeutic aspect. On the basis of this, we can focus more
      on the downstream signaling pathways that are controlled by progesterone. Lipid
      biosynthesis mediated by sterol regulatory element-binding protein-1/fatty acid
      synthase (SREBP-1/FASN) is of utmost importance to the growth and the
      proliferation of EC cells, so we hypothesize that SREBP-1/FASN might be involved
      in suppressing the proliferation and promoting apoptosis in EC cells through the
      effects induced by progesterone. MATERIAL AND METHODS: The Cell Counting Kit-8
      was used to analyze the growth inhibition ratio of Ishikawa cells upon treatment
      with megestrol acetate (MA; MA is a progesterone derivative, also known as
      17alpha-acetoxy-6-dehydro-6-methylprogesterone) and to determine the 50%
      inhibitory concentration. Apoptosis ratio was analyzed by treatment of the cells
      with MA at 50% inhibitory concentration at different time intervals using Annexin
      V-FITC/propidium iodide. The protein and messenger RNA levels of SREBP-1 and FASN
      were compared between the experimental and control groups (MA-treated Ishikawa
      cells were considered to be the experimental group). RESULTS: The experimental
      group showed obvious growth inhibition that was time and concentration dependent.
      The apoptosis ratio was also significantly higher in the experimental group
      compared with the control group (P < 0.01). The protein and messenger RNA levels
      of SREBP-1 and FASN were significantly reduced by MA too. CONCLUSIONS: Sterol
      regulatory element-binding protein-1/FASN is involved in the proliferation
      suppression and apoptosis promotion brought about by MA in Ishikawa cells.

PMID- 24105477
TI  - The effects of Dickkopf-4 on the proliferation, differentiation, and apoptosis of
      osteoblasts.
AB  - The Dickkopf family of proteins is comprised of four members (Dkk1, Dkk2, Dkk3,
      Dkk4) that are known to modulate Wnt/beta-catenin signaling, which is activated
      during bone formation. Although the effects of Dkk1 on Wnt/beta-catenin signaling
      have been well studied, little is known about the effects of Dkk4. Therefore, to
      evaluate the role of Dkk4 in osteoblastogenesis, we used the mouse osteoblastic
      cell line MC3T3-E1, in which Dkk4 expression was suppressed by small interfering
      RNA knockdown. Our results showed that the suppression of Dkk4 expression
      promoted osteoblast proliferation and differentiation and suppressed apoptosis.
      In colony-forming unit alkaline phosphatase assay, Dkk4 knockdown cells possessed
      markedly higher alkaline phosphatase activity compared with Dkk1 knockdown cells.
      Reduced Dkk4 expression also led to the up-regulation of beta-catenin levels,
      beta-catenin/T cell factor activity, and Wnt-target genes. In contrast,
      overexpression of Dkk4 in MC3T3-E1 cells led to inhibition of osteoblast
      differentiation. Our findings reveal that Dkk4 functions as an inhibitor of
      osteoblastogenesis through Wnt/beta-catenin signaling, providing new insights
      into the relationship between Wnt/beta-catenin signaling and Dkk4 in bone
      formation. 

PMID- 24105479
TI  - Novel effects of chromosome Y on cardiac regulation, chromatin remodeling, and
      neonatal programming in male mice.
AB  - Little is known about the functions of chromosome Y (chrY) genes beyond their
      effects on sex and reproduction. In hearts, postpubertal testosterone affects the
      size of cells and the expression of genes differently in male C57BL/6J than in
      their C57.Y(A) counterparts, where the original chrY has been substituted with
      that from A/J mice. We further compared the 2 strains to better understand how
      chrY polymorphisms may affect cardiac properties, the latter being sexually
      dimorphic but unrelated to sex and reproduction. Genomic regions showing
      occupancy with androgen receptors (ARs) were identified in adult male hearts from
      both strains by chromatin immunoprecipitation. AR chromatin immunoprecipitation
      peaks (showing significant enrichment for consensus AR binding sites) were mostly
      strain specific. Measurements of anogenital distances in male pups showed that
      the biologic effects of perinatal androgens were greater in C57BL/6J than in
      C57.Y(A). Although perinatal endocrine manipulations showed that these
      differences contributed to the strain-specific differences in the response of
      adult cardiac cells to testosterone, the amounts of androgens produced by fetal
      testes were not different in each strain. Nonetheless, chrY polymorphisms
      associated in newborn pups' hearts with strain-specific differences in genomic
      regions showing either AR occupancy, accessible chromatin sites, or
      trimethylation of histone H3 Lysine 4 marks, as well as with differential
      expression of 2 chrY-encoded histone demethylases. In conclusion, the effects of
      chrY on adult cardiac phenotypes appeared to result from an interaction of this
      chromosome with the organizational programming effects exerted by the neonatal
      testosterone surge and show several characteristics of being mediated by an
      epigenetic remodeling of chromatin. 

PMID- 24105478
TI  - Exendin-4 improves beta-cell function in autophagy-deficient beta-cells.
AB  - Autophagy is cellular machinery for maintenance of beta-cell function and mass.
      The implication of autophagy failure in beta-cells on the pathophysiology of type
      2 diabetes and its relation to the effect of treatment of diabetes remains
      elusive. Here, we found increased expression of p62 in islets of db/db mice and
      patients with type 2 diabetes mellitus. Treatment with exendin-4, a glucagon like
      peptide-1 receptor agonist, improved glucose tolerance in db/db mice without
      significant changes in p62 expression in beta-cells. Also in beta-cell-specific
      Atg7-deficient mice, exendin-4 efficiently improved blood glucose level and
      glucose tolerance mainly by enhanced insulin secretion. In addition, we found
      that exendin-4 reduced apoptotic cell death and increased proliferating cells in
      the Atg7-deficient islets, and that exendin-4 counteracted thapsigargin-induced
      cell death of isolated islets augmented by autophagy deficiency. Our results
      suggest the potential involvement of reduced autophagy in beta-cell dysfunction
      in type 2 diabetes. Without altering the autophagic state in beta-cells, exendin
      4 improves glucose tolerance associated with autophagy deficiency in beta-cells.
      This is mainly achieved through augmentation of insulin secretion. In addition,
      exendin-4 prevents apoptosis and increases the proliferation of beta-cells
      associated with autophagy deficiency, also without altering the autophagic
      machinery in beta-cells. 

PMID- 24105480
TI  - Antagonistic roles of Dmrt1 and Foxl2 in sex differentiation via estrogen
      production in tilapia as demonstrated by TALENs.
AB  - Transcription activator-like effector nucleases (TALENs) are a powerful approach
      for targeted genome editing and have been proved to be effective in several
      organisms. In this study, we reported that TALENs can induce somatic mutations in
      Nile tilapia, an important species for worldwide aquaculture, with reliably high
      efficiency. Six pairs of TALENs were constructed to target genes related to sex
      differentiation, including dmrt1, foxl2, cyp19a1a, gsdf, igf3, and nrob1b, and
      all resulted in indel mutations with maximum efficiencies of up to 81% at the
      targeted loci. Effects of dmrt1 and foxl2 mutation on gonadal phenotype, sex
      differentiation, and related gene expression were analyzed by histology,
      immunohistochemistry, and real-time PCR. In Dmrt1-deficient testes, phenotypes of
      significant testicular regression, including deformed efferent ducts, degenerated
      spermatogonia or even a complete loss of germ cells, and proliferation of
      steroidogenic cells, were observed. In addition, disruption of Dmrt1 in XY fish
      resulted in increased foxl2 and cyp19a1a expression and serum estradiol-17beta
      and 11-ketotestosterone levels. On the contrary, deficiency of Foxl2 in XX fish
      exhibited varying degrees of oocyte degeneration and significantly decreased
      aromatase gene expression and serum estradiol-17beta levels. Some Foxl2-deficient
      fish even exhibited complete sex reversal with high expression of Dmrt1 and
      Cyp11b2. Furthermore, disruption of Cyp19a1a in XX fish led to partial sex
      reversal with Dmrt1 and Cyp11b2 expression. Taken together, our data demonstrated
      that TALENs are an effective tool for targeted gene editing in tilapia genome.
      Foxl2 and Dmrt1 play antagonistic roles in sex differentiation in Nile tilapia
      via regulating cyp19a1a expression and estrogen production. 

PMID- 24105481
TI  - Triiodothyronine rapidly alters the TSH content and the secretory granules
      distribution in male rat thyrotrophs by a cytoskeleton rearrangement-independent
      mechanism.
AB  - Rapid actions of T3 on TSH synthesis in posttranscriptional steps, such as
      polyadenylation and translation rate, have already been described. The focus of
      this paper was to characterize rapid actions of T3 on TSH secretion and the
      involvement of actin and microtubule cytoskeleton in this process. For that, sham
      operated (SO) and thyroidectomized (Tx) rats were subjected to acute or chronic
      treatment with T3. We observed a disarrangement in microtubule and actin
      cytoskeletons and an increase in Tshb mRNA levels in Tx rats, whereas the total
      TSH protein content was reduced in the pituitary gland as a whole, but increased
      in the secretory granules close to the plasma membrane of thyrotrophs, as well as
      in the extracellular space. The acute T3 dose promoted a rapid increase and
      redistribution of TSH secretory granules throughout the cytoplasm, as well as a
      rearrangement in actin and microtubule cytoskeletons. The T3 chronic treatment
      outcome reinforces the acute effects observed and, additionally, evinces an
      increase in the alpha-tubulin content and a rearrangement in microtubule
      cytoskeleton. Thus, T3 is able to rapidly suppress TSH secretion and, in
      parallel, to promote a rearrangement in actin and microtubules assembly
      throughout the pituitary gland, effects that seem to be independent from each
      other. 

PMID- 24105482
TI  - Inhibition of hippocampal aromatization impairs spatial memory performance in a
      male songbird.
AB  - Recent studies have revealed the presence and regulation of aromatase at the
      vertebrate synapse, and identified a critical role played by presynaptic
      estradiol synthesis in the electrophysiological response to auditory and other
      social cues. However, if and how synaptic aromatization affects behavior remains
      to be directly tested. We have exploited 3 characteristics of the zebra finch
      hippocampus (HP) to test the role of synaptocrine estradiol provision on spatial
      memory function. Although the zebra finch HP contains abundant aromatase
      transcripts and enzyme activity, immunocytochemical studies reveal widespread pre
      and postsynaptic, but sparse to undetectable somal, localization of this enzyme.
      Further, the superficial location of the avian HP makes possible the more
      exclusive manipulation of its neurochemical characteristics without perturbation
      of the neuropil and the resultant induction of astroglial aromatase. Last, as in
      other vertebrates, the HP is critical for spatial memory performance in this
      species. Here we report that local inhibition of hippocampal aromatization
      impairs spatial memory performance in an ecologically valid food-finding task.
      Local aromatase inhibition also resulted in lower levels of estradiol in the HP,
      but not in adjacent brain areas, and was achieved without the induction of
      astroglial aromatase. The observed decrement in acquisition and subsequent memory
      performance as a consequence of lowered aromatization was similar to that
      achieved by lesioning this locus. Thus, hippocampal aromatization, much of which
      is achieved at the synapse in this species, is critical for spatial memory
      performance. 

PMID- 24105484
TI  - Hypothalamic WNT signalling is impaired during obesity and reinstated by leptin
      treatment in male mice.
AB  - The WNT pathway has been well characterized in embryogenesis and tumorigenesis.
      In humans, specific polymorphisms in the T cell-specific transcription factor 7
      and the WNT coreceptor, low-density lipoprotein receptor-related protein-6 (LRP
      6), both prominent components of this pathway, correlate with a higher incidence
      of type 2 diabetes, suggesting that the WNT pathway might be involved in the
      control of adult glucose homeostasis. We previously demonstrated that glycogen
      synthase-kinase-3beta (GSK-3beta), the key enzyme of the WNT pathway, is
      increased in the hypothalamus during obesity and exacerbates high-fat diet
      induced weight gain as well as glucose intolerance. These data suggest that WNT
      action in the hypothalamus might be required for normal glucose homeostasis. Here
      we characterized whether WNT signaling in general is altered in the hypothalamus
      of adult obese mice relative to controls. First we identified expression of
      multiple components of this pathway in the murine arcuate nucleus by in situ
      hybridization. In this region mRNA of ligands and target genes of the WNT pathway
      were down-regulated in obese and glucose-intolerant leptin-deficient mice.
      Similarly, the number of cells immunoreactive for the phosphorylated (active)
      form of the WNT-coreceptor LRP-6 was also decreased in leptin-deficient mice.
      Leptin treatment normalized expression of the WNT-target genes Axin-2 and Cylin
      D1 and increased the number of phospho-LRP-6-immunoreactive cells reaching levels
      of lean controls. Leptin also increased the levels of phosphorylated (inactive)
      GSK-3beta in the arcuate nucleus, and this effect was colocalized to neuropeptide
      Y neurons, suggesting that inactivation of GSK-3beta may contribute to the
      neuroendocrine control of energy homeostasis. Taken together our findings
      identify hypothalamic WNT signaling as an important novel pathway that integrates
      peripheral information of the body's energy status encoded by leptin. 

PMID- 24105483
TI  - The effects of testosterone deprivation and supplementation on proteasomal and
      autophagy activity in the skeletal muscle of the male mouse: differential effects
      on high-androgen responder and low-androgen responder muscle groups.
AB  - Men with prostate cancer who receive androgen deprivation therapy show profound
      skeletal muscle loss. We hypothesized that the androgen deficiency activates not
      only the ubiquitin-proteasome systems but also the autophagy and affects key
      aspects of the molecular cross talk between protein synthesis and degradation.
      Here, 2-month-old male mice were castrated and treated with either testosterone
      (T) propionate or vehicle for 7 days (short term) or 43 days (long term), and
      with and without hydroxyflutamide. Castrated mice showed rapid and profound
      atrophy of the levator ani muscle (high androgen responder) at short term and
      lesser atrophy of the triceps muscle (low androgen responder) at long term.
      Levator ani and triceps muscles of castrated mice showed increased level of
      autophagy markers and lysosome enzymatic activity; only the levator ani showed
      increased proteasomal enzymatic activity. The levator ani muscle of the castrated
      mice showed increased level and activation of forkhead box protein O3A, the
      inhibition of mechanistic target of rapamicyn, and the activation of tuberous
      sclerosis complex protein 2 and 5'-AMP-activated protein kinase. Similar results
      were obtained in the triceps muscle of castrated mice. T rescued the loss of
      muscle mass after orchiectomy and inhibited lysosome and proteasome pathways dose
      dependently and in a seemingly IGF-I-dependent manner. Hydroxyflutamide
      attenuated the effect of T in the levator ani muscle of castrated mice. In
      conclusion, androgen deprivation in adult mice induces muscle atrophy associated
      with proteasomal and lysosomal activity. T optimizes muscle protein balance by
      modulating the equilibrium between mechanistic target of rapamicyn and 5'-AMP
      activated protein kinase pathways. 

PMID- 24105485
TI  - Oral versus intravenous antibiotic treatment for febrile neutropenia in cancer
      patients.
AB  - BACKGROUND: Fever occurring in a neutropenic patient remains a common life
      threatening complication of cancer chemotherapy. The common practice is to admit
      the patient to hospital and treat him or her empirically with intravenous broad
      spectrum antibiotics. Oral therapy could be an alternative approach for selected
      patients. OBJECTIVES: To compare the efficacy of oral antibiotics versus
      intravenous (IV) antibiotic therapy in febrile neutropenic cancer patients.
      SEARCH METHODS: The Cochrane Central Register of Controlled Trials (CENTRAL)
      (2013, Issue 1) in The Cochrane Library, MEDLINE (1966 to January week 4, 2013),
      EMBASE (1980 to 2013 week 4) and LILACS (1982 to 2007). We searched several
      databases for ongoing trials. We checked the conference proceedings of the
      Interscience Conference of Antimicrobial Agents and Chemotherapy (ICAAC) (1995 to
      2007), and all references of included studies and major reviews were scanned.
      SELECTION CRITERIA: Randomised controlled trials (RCTs) comparing oral
      antibiotic(s) to intravenous antibiotic(s) for the treatment of neutropenic
      cancer patients with fever. The comparison between the two could be started
      initially (initial oral) or following an initial course of intravenous antibiotic
      treatment (sequential). DATA COLLECTION AND ANALYSIS: Two review authors
      independently assessed trial eligibility and methodological quality and extracted
      data. Data concerning mortality, treatment failures and adverse events were
      extracted from the included studies assuming an 'intention-to-treat' basis for
      the outcome measures whenever possible. Risk ratios (RR) with 95% confidence
      intervals (CI) were estimated for dichotomous data. Risk of bias assessment was
      also made in line with methodology of The Cochrane Collaboration. MAIN RESULTS:
      Twenty-two trials (3142 episodes in 2372 patients) were included in the analyses.
      The mortality rate was similar when comparing oral to intravenous antibiotic
      treatment (RR 0.95, 95% CI 0.54 to 1.68, 9 trials, 1392 patients, median
      mortality 0, range 0% to 8.8%). Treatment failure rates were also similar (RR
      0.96, 95% CI 0.86 to 1.06, all trials). No significant heterogeneity was shown
      for all comparisons but adverse events. The effect was stable in a wide range of
      patients. Quinolones alone or combined with another antibiotic were used with
      comparable results. Adverse reactions, mostly gastrointestinal, were more common
      with oral antibiotics. AUTHORS' CONCLUSIONS: Based on the present data, oral
      treatment is an acceptable alternative to intravenous antibiotic treatment in
      febrile neutropenic cancer patients (excluding patients with acute leukaemia) who
      are haemodynamically stable, without organ failure, and do not have pneumonia,
      infection of a central line or a severe soft-tissue infection. The wide CI for
      mortality allows the present use of oral treatment in groups of patients with an
      expected low risk for mortality, and further research should be aimed at
      clarifying the definition of low risk patients.

PMID- 24105486
TI  - Messenger RNA vaccine based on recombinant MS2 virus-like particles against
      prostate cancer.
AB  - Prostate cancer (PCa) is the most diagnosed cancer in the western male population
      with high mortality. Recently, alternative approaches based on immunotherapy
      including mRNA vaccines for PCa have shown therapeutic promise. However, for mRNA
      vaccine, several disadvantages such as the instability of mRNA, the high cost of
      gold particles, the limited production scale for mRNA-transfected dendritic cells
      in vitro, limit their development. Herein, recombinant bacteriophage MS2 virus
      like particles (VLPs), which based on the interaction of a 19-nucleotide RNA
      aptamer and the coat protein of bacteriophage MS2, successfully addressed these
      questions, in which target mRNA was packaged by MS2 capsid. MS2 VLP-based mRNA
      vaccines were easily prepared by recombinant protein technology, nontoxic and
      RNase-resistant. We show the packaged mRNA was translated into protein as early
      as 12 hr after phagocytosed by macrophages. Moreover, MS2 VLP-based mRNA vaccines
      induced strong humoral and cellular immune responses, especially antigen-specific
      cytotoxic T-lymphocyte (CTL) and balanced Th1/Th2 responses without upregulation
      of CD4(+) regulatory T cells, and protected C57BL/6 mice against PCa completely.
      As a therapeutic vaccine, MS2 VLP-based mRNA vaccines delayed tumor growth. Our
      results provide proof of concept on the efficacy and safety of MS2 VLP-based mRNA
      vaccine, which provides a new delivery approach for mRNA vaccine and implies
      important clinical value for the prevention and therapy of PCa. 

PMID- 24105487
TI  - Brain magnetic resonance imaging (MRI) pattern recognition in Pol III-related
      leukodystrophies.
AB  - Pol III-related leukodystrophies are caused by mutations in POLR3A and POLR3B
      genes and all share peculiar imaging and clinical features. The objectives of
      this study are (1) to define the neuroradiologic pattern in a cohort of POLR3A
      and POLR3B subjects and (2) to compare the neuroradiologic pattern of Pol III
      related leukodystrophies with other hypomyelinating disorders. The magnetic
      resonance imaging (MRI) examinations of 13 patients with POLR3A and POLR3B
      mutations and of 14 patients with other hypomyelinating disorders were analyzed.
      All the subjects with Pol III-related leukodystrophies presented hypomyelination
      associated with T2 hypointensity of the thalami and/or the pallida. Twelve
      subjects (92%) presented T2 hypointensity of the optic radiations. Cerebellar
      atrophy was observed in most patients (92%). The combination of the analyzed
      criteria identified patients with Pol III-related leukodystrophies with a
      sensitivity of 84.6% and a specificity of 92.9%. 

PMID- 24105488
TI  - Subependymal giant cell astrocytomas in patients with tuberous sclerosis complex:
      considerations for surgical or pharmacotherapeutic intervention.
AB  - Tuberous sclerosis complex is a genetic disorder caused by mutations in either
      the TSC1 or TSC2 gene that can result in the growth of hamartomas in multiple
      organ systems. Subependymal giant cell astrocytomas are slow-growing brain tumors
      associated primarily with tuberous sclerosis complex. They are usually located in
      the ventricles, often near the foramen of Monro, where they can cause an
      obstruction if they grow too large, leading to increased intracranial pressure.
      Surgery to remove a tumor has been the mainstay of treatment but can be
      associated with postoperative morbidity and mortality. Not all tumors and/or
      patients are suitable for surgery. The recent development of mammalian target of
      rapamycin inhibitors that target the pathway affected by TSC1/TSC2 mutations
      offers a novel pharmacotherapeutic option for these patients. We review the
      timing and use of surgery versus pharmacotherapy for the treatment of
      subependymal giant cell astrocytoma in patients with tuberous sclerosis complex. 

PMID- 24105489
TI  - Evidence of programmed cell death induced by reconditioning after cold stress in
      cucumber fruit and possible involvement of ethylene.
AB  - BACKGROUND: Cucumber fruit is susceptible to chilling injury (CI), which could be
      accelerated significantly with subsequent shelf-life. This type of CI culminates
      in deterioration of organs and eventually leads to cell death. In this study,
      evidence of programmed cell death (PCD), involving cell death induced by cold
      stress, was investigated in cucumber. Harvested cucumber (Cucumis sativus L. cv.
      Zhexiu-1) fruits were stored at 2  degrees C for 3, 6 or 9 days and subsequently
      transferred to 20  degrees C for 2 days. RESULTS: Significant cell death
      acceleration was observed upon reconditioning after 9 days' cold stress when the
      hallmark of PCD - DNA laddering - was clearly observed. Further evidence of
      nuclear DNA cleavage was confirmed by the in situ TdT-mediated dUTP nick end
      labeling (TUNEL) assay. Chromatin condensation and nucleus distortion were
      observed by nuclear staining of DPI. Ethylene burst was observed upon
      reconditioning after 9 days of consecutive cold stress. CONCLUSION: The features
      of PCD process induced by reconditioning after cold stress in cucumber fruit may
      be mainly attributed to ethylene burst.

PMID- 24105491
TI  - Association between melanocortin-4 receptor mutations and eating behaviors in
      obese patients: a case--control study.
AB  - Melanocortin-4 receptor (MC4R) gene mutations are involved in the leptin
      melanocortin pathways that control food intake. The effect of these mutations on
      eating behavior phenotypes is still debated. To determine the association between
      functional MC4R mutations and eating behaviors, dietary intake and physical
      activity, we sequenced the MC4R gene in 4653 obese adults. Among them, 19 adults
      carriers of functional MC4R mutation were matched on age, sex and body mass index
      with two randomly-paired controls without MC4R mutation (n=57). We found that
      eating behaviors and physical activity did not differ between groups. In
      particular, cases were not at increased risk of binge eating disorders. Subjects
      carriers of MC4R mutation reported a higher proportion of dietary carbohydrates
      intakes (43.2+/-7.1 and 39.2+/-8.1% of total energy intake, respectively,
      P=0.048) and a lower proportion of dietary lipids (34.3+/-6.7 and 38.5+/-6.7% of
      total energy intake, respectively, P=0.018). In conclusion, mutation carriers
      differ from controls by a higher consumption of carbohydrates counterbalanced by
      a lower consumption of lipids expressed as percentage of total energy intake.
      However, functional MC4R mutations do not have a higher risk of compulsive eating
      contrary to what was previously suggested. 

PMID- 24105493
TI  - Quadrature and number fluctuations produced by parametric devices driven by
      pulsed pumps.
AB  - Two sets of formulas are derived for the field-quadrature and photon-number
      fluctuations (variances and correlations) produced by parametric amplifiers and
      frequency convertors that are driven by pulsed pumps and act on pulsed signals.
      The first set is based on the Green functions for the underlying parametric
      processes, whereas the second is based on the associated Schmidt coefficients and
      modes. These formulas facilitate the modeling and performance optimization of
      parametric devices used in a wide variety of applications. 

PMID- 24105494
TI  - Label-free DNA sensing using millimeter-wave silicon WGM resonator.
AB  - A planar dielectric waveguide based structure for bio-sensing purpose is
      introduced. The proposed device is a silicon-based WGM disc resonator operating
      within the range of 75-110 GHz (W-band). The sensor is an integrated,
      miniaturized, low-cost, and easy-to-fabricate bio-sensor structure. The proposed
      sensor can be used for a number of DNA characterization tasks including Mutation
      in DNA oligonucleotide. Two types of DNAs, single strand and double strand DNAs,
      are successfully tested by our integrated sensor. The measurement repeatability
      and selectivity of the proposed sensor are examined through the different
      experimental lab-tests. 

PMID- 24105492
TI  - Heart failure in patients with atrial fibrillation is associated with a high
      symptom and hospitalization burden: the RealiseAF survey.
AB  - BACKGROUND: Atrial fibrillation (AF) and heart failure (HF) often coexist; the
      consequences of such coexistence are unclear. HYPOTHESIS: HF in patients with AF
      is associated with poor outcomes. METHODS: This post hoc analysis of RealiseAF, a
      survey of AF patients, compared symptoms, hospitalizations, management, and AF
      control in patients with vs without HF. A total of 10,523 AF patients were
      analyzed according to presence/absence of HF. RESULTS: History of HF was present
      in 45.8%, and in more patients with permanent vs persistent, paroxysmal, or first
      episode AF (55.6%, 44.3%, 32.9%, and 29.8%, respectively; P < 0.0001). Patients
      with vs those without history of HF, and patients with HF and reduced ejection
      fraction (HF-REF) vs those with HF and a preserved ejection fraction (HF-PEF),
      had more frequent cardiovascular (CV) risk factors and more severe symptoms.
      Presence vs absence of HF, and HF-REF vs HF-PEF, were associated with lower rates
      of AF control (54.6% vs 62.8% and 49.3% vs 60.3%, respectively; both P < 0.0001).
      The rate-control strategy was used more frequently in HF patients, particularly
      those with HF-REF, than the rhythm-control strategy. CV hospitalizations occurred
      more frequently in patients with HF than those without (41.8% vs 17.5%; P <
      0.001) and more frequently in patients with HF-REF than in those with HF-PEF
      (51.6% vs 35.6%; P < 0.0001). CONCLUSIONS: AF patients with HF, particularly HF
      REF, experience heavy symptom and hospitalization burdens, and have relatively
      low rates of AF control. Further studies are needed to identify ways to improve
      the management and treatment outcomes of this very high-risk patient population.

PMID- 24105495
TI  - Quantum frequency conversion of quantum memory compatible photons to
      telecommunication wavelengths.
AB  - We report an experiment demonstrating quantum frequency conversion of weak light
      pulses compatible with atomic quantum memories to telecommunication wavelengths.
      We use a PPLN nonlinear waveguide to convert weak coherent states at the single
      photon level with a duration of 30 ns from a wavelength of 780 nm to 1552 nm. We
      measure a maximal waveguide internal (external) conversion efficiency eta(int) =
      0.41 (eta(ext) = 0.25), and we show that the signal to noise ratio (SNR) is good
      enough to reduce the input photon number below 1. In addition, we show that the
      noise generated by the pump beam in the crystal is proportional to the spectral
      bandwidth of the device, suggesting that narrower filtering could significantly
      increase the SNR. Finally, we demonstrate that the quantum frequency converter
      can operate in the quantum regime by converting a time-bin qubit and measuring
      the qubit fidelity after conversion.

PMID- 24105496
TI  - Porous silicon integrated Mach-Zehnder interferometer waveguide for biological
      and chemical sensing.
AB  - Optical waveguides comprised of nanoporous materials are uniquely suited for on
      chip sensing applications, because they allow for a target chemical or analyte to
      directly infiltrate the optical material that comprises the core of the
      waveguide. We describe here the fabrication and characterization of nanoporous
      waveguides, and demonstrate their usefulness in measuring small changes in
      refractive index when exposed to a test analyte. We use a process of
      electrochemical etching and laser oxidation to produce channel waveguides and
      integrated on-chip Mach-Zehnder structures, and we compare the responsivity and
      interferometric stability of the integrated sensor to that of a fiber-based
      interferometer. We quantify the detection capability by selectively applying
      isopropanol to a 200 MUm length waveguide segment in one arm of the
      interferometer, which produces a phase shift of 9.7 pi. The integrated
      interferometer is shown to provide a more stable response in comparison to a
      comparable fiber-based implementation.

PMID- 24105497
TI  - Wavelength tunable coherent burst-mode receiver design under transient frequency
      offset.
AB  - Wavelength tunable optical coherent burst-mode receivers (BMR) can offer
      flexibility and sub-wavelength granularity for dynamic WDM networks. A new BMR
      design with dispersion equalizer plus frequency offset estimator is proposed for
      simultaneous dispersion compensation and frequency offset estimation. Its good
      performance is verified by simulations. A training sequence as short as 4 K
      symbols, corresponding to an initialization time of 160 ns, is found to be enough
      to support 200 km transmission distance plus over +/- 5 GHz frequency offset. The
      new BMR design can also work under the case when transient frequency offset from
      wavelength tuning exists in the system.

PMID- 24105498
TI  - Optical data encryption using time-dependent dynamics of refractive index changes
      in LiNbO3.
AB  - We present a method for optical encryption of information, based on the time
      dependent dynamics of writing and erasure of refractive index changes in a bulk
      lithium niobate medium. Information is written into the photorefractive crystal
      with a spatially amplitude-modulated laser beam which when overexposed
      significantly degrades the stored data making it unrecognizable. We show that the
      degradation can be reversed and that a one-to-one relationship exists between the
      degradation and recovery rates. It is shown that this simple relationship can be
      used to determine the erasure time required for decrypting the scrambled index
      patterns. In addition, this method could be used as a straightforward general
      technique for determining characteristic writing and erasure rates in
      photorefractive media. 

PMID- 24105499
TI  - Optimization of efficiency-loss figure of merit in carrier-depletion silicon Mach
      Zehnder optical modulator.
AB  - In this paper we study the optimization of interleaved Mach-Zehnder silicon
      carrier depletion electro-optic modulator. Following the simulation results we
      demonstrate a phase shifter with the lowest figure of merit (modulation
      efficiency multiplied by the loss per unit length) 6.7 V-dB. This result was
      achieved by reducing the junction width to 200 nm along the phase-shifter and
      optimizing the doping levels of the PN junction for operation in nearly fully
      depleted mode. The demonstrated low FOM is the result of both low V(pi)L of ~0.78
      Vcm (at reverse bias of 1V), and low free carrier loss (~6.6 dB/cm for zero
      bias). Our simulation results indicate that additional improvement in performance
      may be achieved by further reducing the junction width followed by increasing the
      doping levels.

PMID- 24105500
TI  - 10 Gbps silicon waveguide-integrated infrared avalanche photodiode.
AB  - We have fabricated monolithic silicon avalanche photodiodes capable of 10 Gbps
      operation at a wavelength of 1550 nm. The photodiodes are entirely CMOS process
      compatible and comprise a p-i-n junction integrated with a silicon-on-insulator
      (SOI) rib waveguide. Photo-generation is initiated via the presence of deep
      levels in the silicon bandgap, introduced by ion implantation and modified by
      subsequent annealing. The devices show a small signal 3 dB bandwidth of 2.0 GHz
      as well as an open eye pattern at 10 Gbps. A responsivity of 4.7 +/- 0.5 A/W is
      measured for a 600 um device at a reverse bias of 40 V. 

PMID- 24105501
TI  - Demonstration of tunable optical delay lines based on apodized grating
      waveguides.
AB  - High-speed and tunable integrated optical delay lines are demonstrated based on
      silicon grating waveguides apodized by the super-Gaussian function. The submicron
      channel waveguides with inward-apodized gratings are fabricated by deep
      ultraviolet optical lithography. Characterization of the compact delay lines
      shows that they offer true-time delays as long as 132 ps, tuning range of ~86 ps,
      and a minimum bit rate of ~13 Gb/s. For lower bit rates, delays as high as 220 ps
      and tuning range of 174 ps are feasible. 

PMID- 24105502
TI  - Slow and stored light by photo-isomerization induced transparency in dye doped
      chiral nematics.
AB  - Decelerating and stopping light is fundamental for optical processing, high
      performance sensor technologies and digital signal treatment, many of these
      applications relying on the ability of controlling the amplitude and phase of
      coherent light pulses. In this context, slow-light has been achieved by various
      methods, as coupling light into resonant media, Brillouin scattering in optical
      fibers, beam coupling in photorefractive and liquid crystal media or engineered
      dispersion in photonic crystals. Here, we present a different mechanism for
      slowing and storing light, which is based on photo-isomerization induced
      transparency of azo-dye molecules hosted in a chiral liquid crystal structure.
      Sharp spectral features of the medium absorption/dispersion, and the long
      population lifetime of the dye metastable state, enable the storage of light
      pulses with a significant retrieval after times much longer than the medium
      response time. 

PMID- 24105503
TI  - Sub-pg mass sensing and measurement with an optomechanical oscillator.
AB  - Mass sensing based on mechanical oscillation frequency shift in micro/nano scale
      mechanical oscillators is a well-known and widely used technique. Piezo-electric,
      electronic excitation/detection and free-space optical detection are the most
      common techniques used for monitoring the minute frequency shifts induced by
      added mass. The advent of optomechanical oscillator (OMO), enabled by strong
      interaction between circulating optical power and mechanical deformation in high
      quality factor optical microresonators, has created new possibilities for
      excitation and interrogation of micro/nanomechanical resonators. In particular,
      radiation pressure driven optomechanical oscillators (OMOs) are excellent
      candidates for mass detection/measurement due to their simplicity, sensitivity
      and all-optical operation. In an OMO, a high quality factor optical mode
      simultaneously serves as an efficient actuator and a sensitive probe for precise
      monitoring of the mechanical eigen-frequencies of the cavity structure. Here, we
      show the narrow linewidth of optomechanical oscillation combined with harmonic
      optical modulation generated by nonlinear optical transfer function, can result
      in sub-pg mass sensitivity in large silica microtoroid OMOs. Moreover by
      carefully studying the impact of mechanical mode selection, device dimensions,
      mass position and noise mechanisms we explore the performance limits of OMO both
      as a mass detector and a high resolution mass measurement system. Our analysis
      shows that femtogram level resolution is within reach even with relatively large
      OMOs. 

PMID- 24105504
TI  - Speckle noise suppression in digital holography by angular diversity with phase
      only spatial light modulator.
AB  - A speckle noise suppression method in digital holography is proposed by the
      angular diversity with a phase-only spatial light modulator (SLM). The minimal
      angular difference of illumination beams is quantitatively analyzed to ensure the
      noncorrelation of any two speckle patterns, and then the phase-only SLM is
      employed to generate a series of tilted illumination beams. Comparing with the
      typical methods, the tilted illumination beams are controlled dynamically and
      accurately, which makes it possible to record a large number of holograms.
      Finally, using an image-plane digital holographic system, 117 holograms are
      recorded respectively, and the synthesized reconstructed images are obtained with
      the greatly suppressed speckle noise which is in good agreement with the
      theoretical results. The experimental results demonstrate the effectiveness,
      repeatability, and practicability of the proposed approach. 

PMID- 24105505
TI  - A high-speed multi-protocol quantum key distribution transmitter based on a dual
      drive modulator.
AB  - We propose a novel source based on a dual-drive modulator that is adaptable and
      allows Alice to choose between various practical quantum key distribution (QKD)
      protocols depending on what receiver she is communicating with. Experimental
      results show that the proposed transmitter is suitable for implementation of the
      Bennett and Brassard 1984 (BB84), coherent one-way (COW) and differential phase
      shift (DPS) protocols with stable and low quantum bit error rate. This could
      become a useful component in network QKD, where multi-protocol capability is
      highly desirable. 

PMID- 24105506
TI  - Silicon photonics plasma-modulators with advanced transmission line design.
AB  - We have investigated two novel concepts for the design of transmission lines in
      travelling wave Mach-Zehnder interferometer based Silicon Photonics depletion
      modulators overcoming the analog bandwidth limitations arising from cross-talk
      between signal lines in push-pull modulators and reducing the linear losses of
      the transmission lines. We experimentally validate the concepts and demonstrate
      an E/O -3 dBe bandwidth of 16 GHz with a 4V drive voltage (in dual drive
      configuration) and 8.8 dB on-chip insertion losses. Significant bandwidth
      improvements result from suppression of cross-talk. An additional bandwidth
      enhancement of ~11% results from a reduction of resistive transmission line
      losses. Frequency dependent loss models for loaded transmission lines and E/O
      bandwidth modeling are fully verified. 

PMID- 24105507
TI  - Fundamentally mode-locked, femtosecond waveguide oscillators with multi-gigahertz
      repetition frequencies up to 15 GHz.
AB  - We demonstrate passively mode-locked Yb(3+)-doped glass waveguide lasers in a
      quasi-monolithic configuration with a maximum pulse repetition frequency up to
      15.2 GHz. A semiconductor saturable absorber mirror (SESAM) is used to achieve
      stable mode-locking around 1050 nm with pulse durations as short as 811 fs and an
      average power up to 27 mW. Different waveguide samples are also employed to
      deliver pulses with repetition rates of 4.9 GHz, 10.4 GHz and 12 GHz with an
      average power of 32 mW, 60 mW and 45 mW, respectively. The group velocity
      dispersion control in the cavity is provided by changing the gap between the
      SESAM and the waveguide end-face to facilitate a soliton mode-locking regime.

PMID- 24105508
TI  - Ge-rich SiGe-on-insulator for waveguide optical modulator application fabricated
      by Ge condensation and SiGe regrowth.
AB  - We have numerically analyzed plasma dispersion effect in a Ge-rich SiGe layer for
      optical modulator applications. Since strain induces reduction in effective
      masses of electron and hole, we expect enhanced plasma dispersion effect in a
      strained Ge-rich SiGe layer. The plasma dispersion effects of Si(0.15)Ge(0.85) on
      Si(0.2)Ge(0.8) for hole and electron are expected to be approximately 3.0 and 1.5
      times larger than those of Si. To realize Ge-rich SiGe-based waveguide optical
      modulators, we have also investigated the fabrication procedure of SiGe-on
      insulator (SGOI) wafers. We have successfully fabricated Ge-rich SGOI wafers
      without any thick SiGe buffer layers by using Ge condensation in conjunction with
      the SiGe regrowth technique. We have evaluated the SGOI by Raman spectroscopy,
      atomic force microscopy (AFM), reflected high energy electron diffraction (RHEED)
      and transmission electron microscopy (TEM). Ge-rich SiGe waveguides have been
      fabricated on the SGOI wafer. The propagation loss was found to be approximately
      13 dB/mm, which can be reduced to be below 2 dB/mm by optimizing the Ge
      condensation process. We expect that strained SiGe grown on the fabricated SGOI
      exhibits more than 2.3 times higher plasma dispersion than Si in case of a
      carrier injection type, suitable for high-performance waveguide optical
      modulators.

PMID- 24105509
TI  - Nanowires and sidewall Bragg gratings in silicon as enabling technologies for
      microwave photonic filters.
AB  - We describe the use of various silicon photonic device technologies to implement
      microwave photonic filters (MPFs). We demonstrate four-wave mixing in a silicon
      nanowire waveguide (SNW) to increase the number of taps for MPFs based on finite
      impulse response filter designs. Using a 12 mm long SNW reduces the footprint by
      five orders of magnitude compared to silica highly nonlinear fiber while only
      requiring approximately two times more input power. We also demonstrate optical
      delays based on serial sidewall Bragg grating arrays and step-chirped sidewall
      Bragg gratings in silicon waveguides. We obtain up to 63 ps delay in discrete
      steps from 15 ps to 32 ps over a wide bandwidth range from 33 nm to at least 62
      nm. These components can be integrated with other silicon-based components such
      as integrated spectral shapers and modulators to realize a fully integrated MPF. 

PMID- 24105510
TI  - Structural optical design of the complex multi-group zoom systems by means of
      matrix optics.
AB  - New matrix formulas for structural optical design have been obtained from
      analysis of derivative of the system matrix in respect to construction parameters
      and movements of components. Functional parameters of the optical system become
      elements of the matrix, presenting working conditions of the optical system.
      Developed methodology of structural design multi-group zoom systems with
      unlimited number of components and with mechanical-electronic compensation is
      presented. Any optical system, such as the objective lens, reproduction system,
      or telescopic system, can be analyzed with this methodology. Kinematics of
      components pertaining to a full tract of the zoom system is determined for a
      discrete number of positions. Three examples of the structural design of complex
      zoom systems with five-components and high zooming ratio are provided. 

PMID- 24105511
TI  - Para-magneto- and electro-optic microcavities for blue wavelength modulation.
AB  - We report on microcavities comprising para-magnetic garnet and electro-optic
      films (MPMEO) for modulation of the polarization rotation angle of light at near
      UV wavelengths with a slight intensity change, with applying a low voltage. The
      MPMEO are composed of para-magnetic garnet and electro-optic films sandwiched
      between two Bragg mirrors. The microcavity states in MPMEO are split and yield
      both the large rotation angle and high optical efficiency. Significant
      enhancement and modulation by applied voltages are verified through a
      conventional matrix calculation approach. High optical efficiency (>90%) and
      large modulation (~90 degree) of the polarization rotation are proved. 

PMID- 24105512
TI  - Measuring the thickness of soap bubbles with phase-shift interferometry.
AB  - A model for the optical path difference introduced by a soap bubble in
      transmission is described. The model is then used with interferometric data to
      solve for the fringe order, and to define a procedure to extract the global film
      thickness in presence of turbulence flows occurring during the drainage process
      due to gravity. Experimental results on soap bubbles examined in single-pass
      phase-shift interferometry are presented. 

PMID- 24105513
TI  - P-side up AlGaInP-based light emitting diodes with dot-patterned GaAs contact
      layers.
AB  - High-brightness p-side up AlGaInP-based red light emitting diodes (LEDs) with dot
      patterned GaAs contact layer and surface rough structure are presented in this
      article. Initial LED structure of p-GaP/AlGaInP/GaAs is epitaxially grown using
      metal organic chemical vapor deposition technique. Using novel twice transferring
      process, the p-GaP layer is remained at the top side as both the current
      spreading and-window layer. Dot patterned GaAs contact dots are formed between
      main structure and rear mirror to improve light reflection and current spreading.
      Moreover, the surface of p-GaP window is further textured by nano-sphere
      lithography technique for improving the light extraction. Significant improvement
      in output power is found for AlGaInP LEDs with GaAs contact dots and roughened p
      GaP window as compared with those of LEDs with traditional n-side up and p-side
      up structures without roughened surfaces. 

PMID- 24105514
TI  - Polarization and incidence insensitive dielectric electromagnetically induced
      transparency metamaterial.
AB  - In this manuscript, we demonstrate numerically classical analogy of
      electromagnetically induced transparency (EIT) with a windmill type metamaterial
      consisting of two dumbbell dielectric resonator. With proper external excitation,
      dielectric resonators serve as EIT bright and dark elements via electric and
      magnetic Mie resonances, respectively. Rigorous numerical analyses reveal that
      dielectric metamaterial exhibits sharp transparency peak characterized by large
      group index due to the destructive interference between EIT bright and dark
      resonators. Furthermore, such EIT transmission behavior keeps stable property
      with respect to polarization and incidence angles. 

PMID- 24105515
TI  - Phase-sensitive imaging of tissue acoustic vibrations using spectrally encoded
      interferometry.
AB  - Acoustic vibrations in tissue are often difficult to image, requiring high-speed
      scanning, high sensitivity and nanometer-scale axial resolution. Here we use
      spectrally encoded interferometry to measure the vibration pattern of two
      dimensional surfaces, including the skin of a volunteer, at nanometric
      resolution, without the need for rapid lateral scanning and with no prior
      knowledge of the driving acoustic waveform. Our results demonstrate the
      feasibility of this technique for measuring tissue biomechanics using simple and
      compact imaging probes. 

PMID- 24105516
TI  - Self-trapped leaky waves in lattices: discrete and Bragg soleakons.
AB  - We propose lattice soleakons: self-trapped waves that self-consistently populate
      slowly-attenuating leaky modes of their self-induced defects in periodic
      potentials. Two types, discrete and Bragg, lattice soleakons are predicted.
      Discrete soleakons that are supported by combination of self-focusing and self
      defocusing nonlinearities propagate robustly for long propagation distances. They
      eventually abruptly disintegrate because they emit power to infinity at an
      increasing pace. In contrast, Bragg soleakons self-trap by only self-focusing
      nonlinearity. Also, they do not disintegrate because they emit power at a
      decreasing rate. 

PMID- 24105517
TI  - 4Pi fluorescence detection and 3D particle localization with a single objective.
AB  - Coherent detection through two opposing objectives (4Pi configuration) improves
      the precision of three-dimensional (3D) single-molecule localization
      substantially along the axial direction, but suffers from instrument complexity
      and maintenance difficulty. To address these issues, we have realized 4Pi
      fluorescence detection by sandwiching the sample between the objective and a
      mirror, and create interference of direct incidence and mirror-reflected signal
      at the camera with a spatial light modulator. Multifocal imaging using this
      single-objective mirror interference scheme offers improvement in the axial
      localization similar to the traditional 4Pi method. We have also devised several
      PSF engineering schemes to enable 3D localization with a single emitter image,
      offering better axial precision than normal single-objective localization methods
      such as astigmatic imaging. 

PMID- 24105519
TI  - Widely tunable Vernier ring laser on hybrid silicon.
AB  - A hybrid silicon tunable Vernier ring laser is designed and fabricated by
      integration of two intra-cavity ring resonators, hybrid III-V-on-silicon gain
      elements, and resistive heaters for thermal tuning. Thermal tuning of more than
      40 nm is demonstrated with side mode suppression ratio greater than 35 dB and
      linewidth of 338 kHz. 

PMID- 24105518
TI  - Directional terahertz emission from corrugated InAs structures.
AB  - The terahertz (THz) radiation from transient dipoles, formed by distinct
      diffusion coefficients between oppositely charged carriers as often observed in
      low band gap semiconductors, propagates with an anisotropic amplitude
      distribution perpendicular to the dipole axis along the diffusive motion. By
      directionally adjusting the electronic diffusion, we conceptualize groove
      patterned THz emitters based on (100) InAs thin films and demonstrate the
      unidirectional radiation. Line-of-sight emission along the surface-normal
      direction is greatly enhanced in a distributed asymmetric trapezoid with its
      period similar to the electronic diffusion length of InAs. This directional
      enhancement is in clear contrast to the constant emission amplitude along the
      lateral direction, regardless of pattern scale, which manifests the role of
      groove patterns as microscale reflectors in laterally corrugating the carrier
      density. In contrast to the rather limited nonlinearity in (100) plane, the
      azimuthal angle dependence of the THz field amplitude in corrugated samples shows
      a combined effect of diffusive transport and second-order nonlinearity, whose
      compositional contributions varies in different structures. 

PMID- 24105520
TI  - Diode-pumped simultaneously Q-switched and mode-locked YVO4/Nd:YVO4/YVO4 crystal
      self-Raman first-Stokes laser.
AB  - A diode-end-pumped simultaneously Q-switched and modelocked self-Raman
      YVO(4)/Nd:YVO(4)/YVO(4) laser at first-Stokes wavelength of 1175.9 nm was
      demonstrated. The shortest mode-locked pulse width of the laser was obtained to
      be ~23.57 ps, with the corresponding timebandwidth product of ~0.51. The maximum
      average output power, the highest pulse energy and the highest peak power were
      obtained to be 1.83 W, 6.1 MUJ and 220 kW, respectively. The nonlinear Raman
      process improved the Q-switched mode-locking performance of the Stokes pulses.

PMID- 24105521
TI  - High power all fiber mid-IR supercontinuum generation in a ZBLAN fiber pumped by
      a 2 MUm MOPA system.
AB  - High power all fiber mid-IR supercontinuum (SC) generation in a ZBLAN fiber
      pumped by a 2 MUm master oscillator power amplifier (MOPA) system is
      demonstrated. A semiconductor saturable absorber mirror (SESAM) passively mode
      locked laser with pulse width of 26 ps at 1960 nm is used as the seed of the MOPA
      system. A laser spectrum extending from ~1.9 MUm to beyond 2.6 MUm is generated
      in a subsequent thulium-doped fiber amplifier (TDFA). Then, the spectrum is
      further broadened to the mid-IR region in the ZBLAN fiber. A mid-IR SC extending
      from 1.9 to 3.9 MUm with 7.11 W average output power is obtained based on a large
      mode area TDFA, the SC power for wavelengths longer than 2.5 MUm is 3.52 W with a
      power ratio of 49.5% with respect to the total SC power. The overall optical
      conversion efficiency from the 790 nm pump of the large mode area TDFA to the
      total SC output is 10.4%. To the best of our knowledge, both the 7.11 W total
      average power and 3.52 W average power in wavelengths beyond 2.5 MUm are the
      highest power ever reported for a mid-IR SC generation in ZBLAN fiber pumped by 2
      MUm fiber lasers and TDFAs. 

PMID- 24105522
TI  - Segmented chirped-pulse Fourier transform submillimeter spectroscopy for
      broadband gas analysis.
AB  - Chirped-pulse Fourier transform spectroscopy has recently been extended to
      millimeter wave spectroscopy as a technique for the characterization of room
      temperature gas samples. Here we present a variation of this technique that
      significantly reduces the technical requirements on high-speed digital
      electronics and the data throughput, with no reduction in the broadband spectral
      coverage and no increase in the time required to reach a given sensitivity level.
      This method takes advantage of the frequency agility of arbitrary waveform
      generators by utilizing a series of low-bandwidth chirped excitation pulses
      paired in time with a series of offset single frequency local oscillators, which
      are used to detect the molecular free induction decay signals in a heterodyne
      receiver. A demonstration of this technique is presented in which a 67 GHz
      bandwidth spectrum of methanol (spanning from 792 to 859 GHz) is acquired in 58
      MUs.

PMID- 24105523
TI  - Overlapping-based optical freeform surface construction for extended lighting
      source.
AB  - The freeform optical system for an extended source was constructed by partially
      overlapping a few numbers of point-source freeform surfaces (PFSs) and extracting
      their contour. Each PFS redistributed the Lambertian emission of a point source
      into the prescribed light distribution or more frequently into a modified
      distribution. By adjusting the relative positions of the PFSs and the pattern of
      the modified light distribution, the optimized freeform surface could be
      obtained. As an example, an optical system with a height only four times the
      source radius is designed for achieving a uniform-illuminance distribution on the
      target. The optimized freeform surface was formed by two PFSs. The virtue-point
      sources of the PFSs were located symmetrically on the extended source with a
      distance of a quarter of the source diameter from each other. Each PFS achieved
      an increasing-illuminance distribution. The illumination uniformity of this model
      can be improved by 55.4%, while the optical efficiency within the target area is
      maintained above 80%. 

PMID- 24105524
TI  - Wired/wireless access integrated RoF-PON with scalable generation of multi
      frequency MMWs enabled by tunable optical frequency comb.
AB  - In this paper, a novel wired/wireless access integrated radio-over-fiber passive
      optical network (RoF-PON) system that utilizes scalable multiple-frequency
      millimeter-wave (MF-MMW) generation based on tunable optical frequency comb
      (TOFC) is proposed. The TOFC is performed by cascading a phase modulator (PM) and
      two intensity modulators (IMs), and with proper selection of the peak-to-peak
      voltage of the PM, a flat and effective optical comb with tens of frequency lines
      is achieved. The MF-MMWs are generated by beating the optical comb line pairs
      with an interval about 60 GHz. The feasibility and scalability of the proposed
      wired/wireless access integrated RoF-PON scheme are confirmed by the simulations
      of simultaneous distribution of wired and wireless data with the proposed
      multiple frequency MMW generation technology.

PMID- 24105525
TI  - Probability theory for 3-layer remote sensing in ideal gas law environment.
AB  - We extend the probability model for 3-layer radiative transfer [Opt. Express 20,
      10004 (2012)] to ideal gas conditions where a correlation exists between
      transmission and temperature of each of the 3 layers. The effect on the
      probability density function for the at-sensor radiances is surprisingly small,
      and thus the added complexity of addressing the correlation can be avoided. The
      small overall effect is due to (a) small perturbations by the correlation on
      variance population parameters and (b) cancellation of perturbation terms that
      appear with opposite signs in the model moment expressions.

PMID- 24105526
TI  - Nanocavity-based self-frequency conversion laser.
AB  - Self-frequency conversion (SFC), where both laser oscillation and nonlinear
      frequency conversion occurs in the same laser crystal, has been used to
      efficiently extend the operational wavelength of lasers. Downsizing of the cavity
      mode volume (V) and increasing the quality factor (Q) could lead to a more
      efficient conversion process, mediated by enhanced n-th order nonlinearities that
      generally scale as (Q/V)(n). Here, we demonstrate nanocavity-based SFC by
      utilizing photonic crystal nanocavity quantum dot lasers. The high Q and small V
      supported in semiconductor-based nanocavities facilitate efficient SFC to
      generate visible light, even with only a few photons present in the laser cavity.
      The combined broadband quantum dot gain and small device footprint enables the
      monolithic integration of 26 different-color nanolasers (spanning 493-627 nm)
      within a micro-scale region. These nanolasers provide a new platform for studying
      few-photon nonlinear optics, and for realizing full-color lasers on a single
      semiconductor chip.

PMID- 24105527
TI  - The multiparty coherent channel and its implementation with linear optics.
AB  - The continuous-variable coherent (conat) channel is a useful resource for
      coherent communication, supporting coherent teleportation and coherent superdense
      coding. We extend the conat channel to multiparty conditions by proposing
      definitions on multiparty position-quadrature and momentum-quadrature conat
      channel. We additionally provide two methods to implement this channel using
      linear optics. One method is the multiparty version of coherent communication
      assisted by entanglement and classical communication (CCAECC). The other is
      multiparty coherent superdense coding. 

PMID- 24105528
TI  - An optical fiber Bragg grating force sensor for monitoring sub-bandage pressure
      during compression therapy.
AB  - Graduated compression bandaging of the lower limbs is the primary therapy for
      venous leg ulcers with its efficacy believed to be predominantly dependent on the
      amount and the distribution of the compressive pressure applied. There has been
      on-going demand for an ideal sensor to facilitate in-vivo monitoring of the sub
      bandage pressure. Several methods and devices have been reported but each has its
      limitations, such as bulkiness, low tolerance to movement, susceptible to thermal
      noise and single point sensing. An optical fiber force sensor is demonstrated,
      consisting of two arrays of fiber Bragg grating (FBG) entwined in a double helix
      form and packaged with contact-force sensitivity. This sensor array has inherent
      temperature immunity and is capable of real-time, distributed sensing of sub
      bandage pressure. The calibration results of the sensor array, as well as the
      validation human trial results, are presented. 

PMID- 24105530
TI  - Tilted elemental image array generation method for moire-reduced computer
      generated integral imaging display.
AB  - In this paper, we propose a tilted elemental image array generation method for
      computer generated integral imaging display with reduced moire patterns. The
      pixels of the tilted elemental image array are divided into border pixels and
      effective pixels. According to the optimal tilted angle, the effective pixels are
      arranged with uniform arrangement. Also, a pixel mapping method is proposed.
      Appropriate experiments are carried out and the experimental results show that
      not only the color moire patterns are reduced remarkably, but also the resolution
      of the reconstructed 3D images are improved through the proposed method. 

PMID- 24105529
TI  - Self-supporting polymer pipes for low loss single-mode THz transmission.
AB  - In this paper, a self-supporting polymer pipe is proposed and investigated for
      THz wave transmission. Utilizing fiber drawing technique for polymer fiber, self
      supporting pipes with wall thickness of several tens micrometers can be
      fabricated using polymethylmethacrylate (PMMA). The guiding mechanism and
      transmission characteristics of the self-supporting pipes are investigated
      theoretically, showing that it can support single-mode transmission at THz band.
      The self-supporting pipe samples with different structure parameters are
      fabricated and measured experimentally, showing that it can support single HE(11)
      mode transmission. Theoretical analysis and experimental results show that this
      self-supporting polymer pipe is a promising candidate for low loss THz fibers.

PMID- 24105531
TI  - Wideband wavelength conversion of 16 Gbaud 16-QAM and 5 Gbaud 64-QAM signals in a
      semiconductor optical amplifier.
AB  - We demonstrate wavelength conversion based on four-wave mixing in a semiconductor
      optical amplifier of signals with quadrature amplitude modulation (QAM). We first
      demonstrate wavelength conversion of 16 Gbaud 16-QAM signals over the entire C
      band using two co-polarized pumps with low power penalty at the forward error
      correction threshold (FEC) for a wide range of input optical-signal-to-noise
      ratio (OSNR). We also demonstrate for the first time wavelength conversion of 5
      Gbaud 64-QAM signals in a semiconductor optical amplifier with bit-error rate
      below the FEC threshold over the entire C-band and investigate the dependence of
      the power penalty on input OSNR with a single pump configuration. 

PMID- 24105532
TI  - Photonic band structures of periodic arrays of pores in a metallic host: tight
      binding beyond the quasistatic approximation.
AB  - We have calculated the photonic band structures of metallic inverse opals and of
      periodic linear chains of spherical pores in a metallic host, below a plasma
      frequency omegap. In both cases, we use a tight-binding approximation, assuming a
      Drude dielectric function for the metallic component, but without making the
      quasistatic approximation. The tight-binding modes are linear combinations of the
      single-cavity transverse magnetic (TM) modes. For the inverse-opal structures,
      the lowest modes are analogous to those constructed from the three degenerate
      atomic p-states in fcc crystals. For the linear chains, in the limit of small
      spheres compared to a wavelength, the results bear some qualitative resemblance
      to the dispersion relation for metal spheres in an insulating host, as calculated
      by Brongersma et al. [Phys. Rev. B 62, R16356 (2000)]. Because the
      electromagnetic fields of these modes decay exponentially in the metal, there are
      no radiative losses, in contrast to the case of arrays of metallic spheres in
      air. We suggest that this tight-binding approach to photonic band structures of
      such metallic inverse materials may be a useful approach for studying photonic
      crystals containing metallic components, even beyond the quasistatic
      approximation.

PMID- 24105533
TI  - Multi-frame super-resolution algorithm for complex motion patterns.
AB  - Multi-frame super-resolution algorithms offer resolution enhancement for
      sequences of images with sampling limited resolution. However, classical
      approaches have been constrained by the accuracy of motion estimation while
      nonlocal approaches that use implicit motion estimation have attained only modest
      resolution improvement. In this paper, we propose a new multi-frame optical flow
      based super-resolution algorithm, which provides significant resolution
      enhancement for image sequences containing complex motion. The algorithm uses the
      standard camera image formation model and a variational super-resolution
      formulation with an anisotropic smoothness term adapting to local image
      structures. The key elements enabling super-resolution of complex motion patterns
      are the computation of two-way optical flow between the images and use of two
      corresponding uncertainty measures that approximate the optical flow
      interpolation error. Using the developed algorithm, we are able to demonstrate
      super-resolution of images for which optical flow estimation experiences near
      breakdown, due to the complexity of the motion patterns and the large magnitudes
      of the displacements. In comparison, we show that for these images some
      conventional super-resolution approaches fail, while others including nonlocal
      super-resolution technique produce distortions and provide lower (1-1.8 dB) image
      quality enhancement compared to the proposed algorithm.

PMID- 24105534
TI  - Dynamic electro-optic response of graphene/graphitic flakes in nematic liquid
      crystals.
AB  - Electric field induced dynamic reorientation phenomenon of graphene/graphitic
      flakes in homogeneously aligned nematic liquid crystal (NLC) medium has been
      demonstrated by optical microscopy. The flakes reorient from parallel to
      perpendicular configuration with respect to boundary plates of confining cells
      for an applied field strength of as low as tens of millivolt per micrometer.
      After field removal the reoriented flakes recover to their initial state with the
      help of relaxation of NLC. Considering flake reorientation phenomenon both in
      positive and negative dielectric anisotropy NLCs, the reorientation process
      depends on interfacial Maxwell-Wagner polarization and NLC director
      reorientation. We propose a phenomenological model based on electric field
      induced potential energy of graphitic flakes and coupling contribution of
      positive NLC to generate the rotational kinetic energy for flake reorientation.
      The model successfully explains the dependence of flake reorientation time over
      flake shape anisotropy, electric-field strength, and flake area. Using present
      operating scheme it is possible to generate dark field-off state and bright field
      on state, having application potential for electro-optic light modulation
      devices. 

PMID- 24105535
TI  - Fully updatable three-dimensional holographic stereogram display device based on
      organic monolithic compound.
AB  - Holographic technique is a unique method to reproduce object on a device in three
      dimensions (3D). It allows us real 3D images with full parallax without special
      eye glasses or any special optical devices. we present fully updatable
      holographic 3D display system using a holographic stereographic technique with a
      transparent optical device of poly(methylmethacrylate) doped organic compound of
      3-[(4-nitrophenyl)azo]-9H-carbazole-9-ethanol (NACzE). 100 elemental holograms
      which are a series of pictures of object took from different angles can
      completely reproduce updatable entire hologram of object. Former hologram of
      object can be over-recorded and immediately replaced by new hologram of object
      without erasing process. Typical recording time for an elemental hologram is 200
      ms, and total recording time including translational stage movement for 100
      elemental holograms is 28 s. The present system with preferred memory is a good
      candidate for 3D signage application. 

PMID- 24105536
TI  - All-optical amplitude-phase transmultiplexing of RZ-OOK and RZ-BPSK to RZ-QPSK by
      polarization-insensitive XPM using a nonlinear birefringent AlGaAs waveguide.
AB  - Polarization-insensitive (PI) phase-transmultiplexing (PTM) of a 10-Gb/s return
      to-zero ON-OFF keying (RZ-OOK) pump and a 10-Gb/s RZbinary phase-shift keying (RZ
      BPSK) probe to 20-Gb/s RZ-quadrature-PSK (RZ-QPSK) has been successfully
      demonstrated for the first time in a passive, birefringent AlGaAs waveguide,
      utilizing PI cross-phase modulation (PI-XPM). For differential QPSK (DQPSK)
      detection, a 10 - 9-BER pre-amplified receiver sensitivity penalty of ~ 2.5 dB
      for the in-phase component and ~ 4.9 dB for the quadrature component were found.
      The penalties were relative to the FPGA-precoded RZ-DQPSK baseline for a pump
      probe detuning of ~ 12 nm, when the probe state of polarization was scrambled and
      the pump was launched off-axis into the waveguide.

PMID- 24105537
TI  - Heterodyne interferometer for absolute amplitude vibration measurements with
      femtometer sensitivity.
AB  - A heterodyne interferometer for highly sensitive vibration measurements in the
      range 100 kHz - 1.3GHz is presented. The interferometer measures absolute
      amplitude and phase. The signal processing of the setup is analyzed and described
      in detail to optimize noise suppression. A noise floor of 7.1 fm/Hz(1/2) at 21
      MHz was achieved experimentally where the bandwidth is the inverse of all time
      needed for filter settling and signal sampling. To demonstrate the
      interferometer, measurements up to 220 MHz were performed on arrays of capacitive
      micromachined ultrasonic transducers (CMUTs). The measurements provided detailed
      information e.g. about the frequency response, vibration patterns and array
      uniformity. Such measurements are highly valuable in the design process of
      ultrasonic transducers.

PMID- 24105538
TI  - Projection angle dependence in grating-based X-ray dark-field imaging of ordered
      structures.
AB  - Over the recent years X-ray differential phase-contrast imaging was developed for
      the hard X-ray regime as produced from laboratory X-ray sources. The technique
      uses a grating-based Talbot-Lau interferometer and was shown to yield image
      contrast gain, which makes it very interesting to the fields of medical imaging
      and non-destructive testing, respectively. In addition to X-ray attenuation
      contrast, the differential phase-contrast and dark-field images provide different
      structural information about a specimen. For the dark-field even at length scales
      much smaller than the spatial resolution of the imaging system. Physical
      interpretation of the dark-field information as present in radiographic and
      tomographic (CT) images requires a detailed look onto the geometric orientation
      between specimen and the setup. During phase-stepping the drop in intensity
      modulation, due to local scattering effects within the specimen is reproduced in
      the dark-field signal. This signal shows strong dependencies on micro-porosity
      and micro-fibers if these are numerous enough in the object. Since a grating
      interferometer using a common unidirectional line grating is sensitive to X-ray
      scattering in one plane only, the dark-field image is influenced by the fiber
      orientations with respect to the grating bars, which can be exploited to obtain
      anisotropic structural information. With this contribution, we attempt to extend
      existing models for 2D projections to 3D data by analyzing dark-field contrast
      tomography of anisotropically structured materials such as carbon fiber
      reinforced carbon (CFRC). 

PMID- 24105539
TI  - Optically tunable and detectable magnetoelectric effects in the composite
      consisting of magnetic thin films and InGaN/GaN multiple quantum wells.
AB  - An optically tunable and detectable magnetoeletric (ME) effect has been
      discovered in the composite consisting of InGaN/GaN multiple quantum wells and
      magnetostrictive ferromagnetic Ni or FeCo thin films at room temperature. Due to
      the interactively optical and piezoelectric properties of nitride semiconductors,
      this composite provides an intriguing optically accessible system, in which the
      magnetoelectric effect can be both easily tuned and detected. The underlying
      mechanism can be well accounted for by the interplay among magnetostrictive,
      piezoelectric and optical transition. It thus offers a new paradigm to generate
      artificial material systems with magnetic/electric/optical inter
      related/controllable properties. 

PMID- 24105540
TI  - Pre- and post-processing for tomographic reconstruction of terahertz time-domain
      spectroscopy.
AB  - Reflection-type terahertz tomography is obtained using time-domain spectroscopy.
      Due to different velocities of the terahertz ray in free space and inside a
      sample, the tomographic transverse plane is not obtained by a simple
      reconstruction using time index. A pre-processing method is proposed to
      compensate for the different velocities of the terahertz ray for tomographic
      reconstruction. Maximum intensity projection, averaging, and short-time Fourier
      transform are proposed as post-processing methods along the depth direction for
      the terahertz tomography. Log-scale display is also suggested for a better
      visualization. Some experimental results with the pre- and post-processing are
      demonstrated. 

PMID- 24105541
TI  - VCSEL-based, high-speed, in situ TDLAS for in-cylinder water vapor measurements
      in IC engines.
AB  - We report the first application of a vertical-cavity surfaceemitting laser
      (VCSEL) for calibration- and sampling-free, high-speed, in situ H2O concentration
      measurements in IC engines using direct TDLAS (tunable diode laser absorption
      spectroscopy). Measurements were performed in a single-cylinder research engine
      operated under motored conditions with a time resolution down to 100 MUs (i.e.,
      1.2 crank angle degrees at 2000 rpm). Signal-to-noise ratios (1sigma) up to 29
      were achieved, corresponding to a H2O precision of 0.046 vol.% H2O or 39 ppm . m.
      The modulation frequency dependence of the performance was investigated at
      different engine operating points in order to quantify the advantages of VCSEL
      against DFB lasers.

PMID- 24105542
TI  - Experimental demonstration of a multi-wavelength distributed feedback
      semiconductor laser array with an equivalent chirped grating profile based on the
      equivalent chirp technology.
AB  - We report, to the best of our knowledge, the first realization of a multi
      wavelength distributed feedback (DFB) semiconductor laser array with an
      equivalent chirped grating profile based on equivalent chirp technology. All the
      lasers in the laser array have an identical grating period with an equivalent
      chirped grating structure, which are realized by nonuniform sampling of the
      gratings. Different wavelengths are achieved by changing the sampling functions.
      A multi-wavelength DFB semiconductor laser array is fabricated and the lasing
      performance is evaluated. The results show that the equivalent chirp technology
      is an effective solution for monolithic integration of a multi-wavelength laser
      array with potential for large volume fabrication. 

PMID- 24105543
TI  - Photonic band gap in isotropic hyperuniform disordered solids with low dielectric
      contrast.
AB  - We report the first experimental demonstration of a TE-polarization photonic band
      gap (PBG) in a 2D isotropic hyperuniform disordered solid (HUDS) made of
      dielectric media with a dielectric index contrast of 1.6:1, very low for PBG
      formation. The solid is composed of a connected network of dielectric walls
      enclosing air-filled cells. Direct comparison with photonic crystals and
      quasicrystals permitted us to investigate band-gap properties as a function of
      increasing rotational isotropy. We present results from numerical simulations
      proving that the PBG observed experimentally for HUDS at low index contrast has
      zero density of states. The PBG is associated with the energy difference between
      complementary resonant modes above and below the gap, with the field
      predominantly concentrated in the air or in the dielectric. The intrinsic
      isotropy of HUDS may offer unprecedented flexibilities and freedom in
      applications (i. e. defect architecture design) not limited by crystalline
      symmetries. 

PMID- 24105544
TI  - Long-term stable, sub-femtosecond timing distribution via a 1.2-km polarization
      maintaining fiber link: approaching 10(-21) link stability.
AB  - Long-term stable, sub-femtosecond timing distribution over a 1.2-km polarization
      maintaining (PM) fiber-optic link using balanced optical cross-correlators for
      link stabilization is demonstrated. Novel dispersion-compensating PM fiber was
      developed to construct a dispersion-slope-compensated PM link, which eliminated
      slow timing drifts and jumps previously induced by polarization mode dispersion
      in standard single-mode fiber. Numerical simulations of nonlinear pulse
      propagation in the fiber link confirmed potential sub-100-as timing stability for
      pulse energies below 70 pJ. Link operation for 16 days showed ~0.6 fs RMS timing
      drift and during a 3-day interval only ~0.13 fs drift, which corresponds to a
      stability level of 10(-21).

PMID- 24105545
TI  - Controlling the duty cycle of the eigenstates in laser with multiple optical
      feedback.
AB  - The polarization dynamics of a quasi-isotropic single-mode laser subjected to
      multiple optical feedback is presented. The variable duty cycle of two
      eigenstates is observed in high-frequency optical fringes. The high-frequency
      optical fringes are induced by the multiple reflections in the asymmetry feedback
      cavity. The duty cycle of two eigenstates can be controlled easily by adjusting
      the position of polarization flipping due to the residual stress of laser mirror.
      Particularly, when the frequency difference results from residual stress is
      reduced to 1.5MHz, the position of polarization flipping moves to the edge of
      each fringe which can be used to measure small displacement with direction
      sensitivity and high resolution. 

PMID- 24105546
TI  - Direct observation of keyhole characteristics in deep penetration laser welding
      with a 10 kW fiber laser.
AB  - Keyhole formation is a prerequisite for deep penetration laser welding.
      Understanding of the keyhole dynamics is essential to improve the stability of
      the keyhole. Direct observation of the keyhole during deep penetration laser
      welding of a modified "sandwich" specimen with a 10 kW fiber laser is presented.
      A distinct keyhole wall and liquid motion along the wall are observed directly
      for the first time. The moving liquid "shelf" on the front keyhole wall and the
      accompanying hydrodynamic and vapor phenomena are observed simultaneously. Micro
      droplets torn off the keyhole wall and the resultant bursts of vapor are also
      visualized. The hydrodynamics on the keyhole wall has a dominant effect on the
      weld defects. The emission spectrum inside the keyhole is captured accurately
      using a spectrometer to calculate the characteristics of the keyhole plasma
      plume. 

PMID- 24105547
TI  - Single-focus x-ray zone plate by stagger arrangement of zones.
AB  - In this paper a novel single-focus x-ray zone plate is proposed by stagger
      arrangement of zones, which would be technically easier to manufacture.
      Theoretical design shows that the transmission function of the plate is a cosine
      function of radius, like that of a Gabor zone plate. Numerical simulation at the
      wavelength of 0.275 nm shows that the plate is of single-order focusing, with
      spatial resolution limit the same as that of the corresponding conventional zone
      plate, and the first-order diffraction efficiency of 11.5%. The plate can also
      work for single-order focusing at other x-ray wavelengths. 

PMID- 24105548
TI  - Strong confinement of light in low index materials: the Photon Cage.
AB  - New photonic microstructures are proposed for an efficient light trapping in low
      index media. Cylindrical hollow cavities formed by bending a photonic crystal
      membrane are designed. Using numerical simulations, strong confinement of photons
      is demonstrated for very open resonators. The resulting strong light matter
      interaction can be exploited in optical devices comprising an active material
      embedded in a low index matrix like polymer or even gaz. 

PMID- 24105549
TI  - DFG-based mid-IR generation using a compact dual-wavelength all-fiber amplifier
      for laser spectroscopy applications.
AB  - We demonstrate a compact mid-infrared (mid-IR) radiation source based on
      difference frequency generation (DFG) in periodically poled lithium niobate
      (PPLN) crystal. The system incorporates a dual-wavelength master oscillator power
      amplifier (MOPA) source capable of simultaneous amplification of 1064 nm and 1548
      nm signals in a common active fiber co-doped with erbium and ytterbium ions. Two
      low-power seed lasers were amplified by a factor of 14.4 dB and 23.7 dB for 1064
      nm and 1548 nm, respectively and used in a nonlinear DFG setup to generate 1.14
      mW of radiation centered at 3.4 MUm. The system allowed for open-path detection
      of methane (CH(4)) in ambient air with estimated minimum detectable concentration
      at a level of 26 ppbv.

PMID- 24105550
TI  - Experimental quasi-single-photon transmission from satellite to earth.
AB  - Free-space quantum communication with satellites opens a promising avenue for
      global secure quantum network and large-scale test of quantum foundations.
      Recently, numerous experimental efforts have been carried out towards this
      ambitious goal. However, one essential step--transmitting single photons from the
      satellite to the ground with high signal-to-noise ratio (SNR) at realistic
      environments--remains experimental challenging. Here, we report a direct
      experimental demonstration of the satellite-ground transmission of a quasi-single
      photon source. In the experiment, single photons (~0.85 photon per pulse) are
      generated by reflecting weak laser pulses back to earth with a cube-corner retro
      reflector on the satellite CHAMP, collected by a 600-mm diameter telescope at the
      ground station, and finally detected by single-photon counting modules after 400
      km free-space link transmission. With the help of high accuracy time
      synchronization, narrow receiver field-of-view and high-repetition-rate pulses
      (76 MHz), a SNR of better than 16:1 is obtained, which is sufficient for a secure
      quantum key distribution. Our experimental results represent an important step
      towards satellite-ground quantum communication.

PMID- 24105551
TI  - Design and analysis of ultra-compact EO polymer modulators based on hybrid
      plasmonic microring resonators.
AB  - Ultra-compact EO polymer modulators based on hybrid plasmonic microring
      resonators are proposed, simulated and analyzed. Comparing with Si slot microring
      modulator, hybrid plasmonic microring modulator shows about 6-times enhancement
      of the figure of merit when the bending radius is around 510 nm, due to its much
      larger intrinsic quality factor in sub-micron radius range. Influences of the EO
      polymer height and Si height on the device's performance are analyzed and optimal
      design is given. When operating with a bias of 3.6 V, the proposed device has
      optical modulation amplitude of 0.8 and insertion loss of about 1 dB. The
      estimated power consumption is about 5 fJ/bit at 100 GHz.

PMID- 24105552
TI  - Root cause analysis and solution to the degradation of wavelength division
      multiplexing (WDM) couplers in high power fiber amplifier system.
AB  - In the evaluation a fused biconical taper 1480/1580 nm WDM's ability to handle
      high power cascaded Raman laser throughput (>100 W) a significant degradation in
      performance was observed. A systematic root cause investigation was conducted and
      it is experimentally confirmed that the WDM degradation was caused by an
      interaction between the high power 1480 nm line, an out-of-band Stokes line, and
      the -OH content of the glass optical fiber. Slanted fiber Bragg grating (SFBG)
      was introduced to filter out the 1390 nm out-of-band Stokes line in an attempt to
      avoid this interaction. Ultimately a series of tests were conducted and it was
      confirmed that the addition of a 1390 nm SFBG in between a high power Raman laser
      and the high power WDM has successfully prevented the degradation which therefore
      allowed the continued high power operation of the WDM. NAVAIR Public Release SPR
      2013-469 Distribution Statement A-"Approved for Public release; distribution is
      unlimited". 

PMID- 24105553
TI  - Mode-locked pulse generation from an all-fiberized, Tm-Ho-codoped fiber laser
      incorporating a graphene oxide-deposited side-polished fiber.
AB  - An in-depth experimental investigation was conducted into the use of a graphene
      oxide-based saturable absorber implemented on a side-polished fiber platform for
      femtosecond pulse generation in the 2 MUm region. First, it was experimentally
      shown that an all-fiberized thulium-holmium (Tm-Ho)-codoped fiber ring laser with
      reduced cavity length can produce stable femtosecond pulses by incorporating a
      graphene oxide-deposited side-polished fiber. Second, the measurement accuracy
      issue in obtaining a precise pulse-width value by use of an autocorrelator
      together with a silica fiber-based 2 MUm-band amplifier was investigated. It
      showed that the higher-order soliton compression effect caused by the combination
      of anomalous dispersion and Kerr nonlinearity can provide incorrect pulse-width
      information. Third, an experimental investigation into the precise role of the
      graphene oxide-deposited side-polished fiber was carried out to determine whether
      its polarization-dependent loss (PDL) can be a substantial contributor to mode
      locking through nonlinear polarization rotation. By comparing its performance
      with that of a gold-deposited side-polished fiber, the PDL contribution to mode
      locking was found to be insignificant, and the dominant mode-locking mechanism
      was shown to be saturable absorption due to mutual interaction between the
      evanescent field of the oscillated beam and the deposited graphene oxide
      particles. 

PMID- 24105554
TI  - Ray-leakage-free sawtooth-shaped planar lightguide solar concentrators.
AB  - This paper details the design of a ray-leakage-free sawtooth-shaped planar
      lightguide solar concentrator. The concentrator combines Unger's dimpled planar
      lightguide solar concentrators [1] with a prism array dimpled planar lightguide
      solar concentrator. The use of a sawtooth-shaped boundary on the planar
      lightguide prevents leakages of the guiding ray after multiple reflections in the
      lightguide. That is, the proposed solar concentrator can achieve a higher
      geometrical concentration ratio, while maintaining a high optical efficiency at
      the same time. Numerical results show that the proposed sawtooth-shaped planar
      lightguide solar concentrator achieves 2300x geometrical concentration ratio
      without any guiding ray-leakages from the planar lightguide. 

PMID- 24105555
TI  - Third-order random lasing via Raman gain and Rayleigh feedback within a half-open
      cavity.
AB  - Third-order random lasing operating in 1670 nm spectral band is experimentally
      demonstrated for the first time to the best of our knowledge, with only 2.45 W
      pump threshold. The lasing cavity is formed by G.652 fiber and fiber loop mirrors
      (FLMs), while the former acts as the distributed reflector and the latter acts as
      the point reflector. The G.652 fiber and the FLMs are connected via a multi-band
      wavelength-division-multiplexer, which ensures each of the three Raman Stokes
      components generated in the long fiber is routed to one FLM and then reflected
      back with minimum loss. Unlike existing half-open random lasing cavities using
      fiber Bragg gratings, the reflection bandwidth of FLMs is wide enough to preserve
      the intrinsic spectral features of each lasing bands, providing a valuable
      platform to study the mechanism of high-order random lasing in fibers. Also, the
      reflection efficiency can be treated as an invariant as the pump power grows,
      significantly reducing the threshold of high-order random lasing. The stationary
      model is used to calculate the output power, and the results fit the experimental
      data well.

PMID- 24105556
TI  - Motion-blurred star acquisition method of the star tracker under high dynamic
      conditions.
AB  - The star tracker is one of the most promising attitude measurement devices used
      in spacecraft due to its extremely high accuracy. However, high dynamic
      performance is still one of its constraints. Smearing appears, making it more
      difficult to distinguish the energy dispersive star point from the noise. An
      effective star acquisition approach for motion-blurred star image is proposed in
      this work. The correlation filter and mathematical morphology algorithm is
      combined to enhance the signal energy and evaluate slowly varying background
      noise. The star point can be separated from most types of noise in this manner,
      making extraction and recognition easier. Partial image differentiation is then
      utilized to obtain the motion parameters from only one image of the star tracker
      based on the above process. Considering the motion model, the reference window is
      adopted to perform centroid determination. Star acquisition results of real on
      orbit star images and laboratory validation experiments demonstrate that the
      method described in this work is effective and the dynamic performance of the
      star tracker could be improved along with more identified stars and guaranteed
      position accuracy of the star point. 

PMID- 24105557
TI  - Enhancement of broadband optical absorption in photovoltaic devices by band-edge
      effect of photonic crystals.
AB  - We numerically investigate broadband optical absorption enhancement in thin, 400
      nm thick microcrystalline silicon (uc-Si) photovoltaic devices by photonic
      crystals (PCs). We realize absorption enhancement by coupling the light from the
      free space to the large area resonant modes at the photonic band-edge induced by
      the photonic crystals. We show that multiple photonic band-edge modes can be
      produced by higher order modes in the vertical direction of the Si photovoltaic
      layer, which can enhance the absorption on multiple wavelengths. Moreover, we
      reveal that the photonic superlattice structure can produce more photonic band
      edge modes that lead to further optical absorption. The absorption average in
      wavelengths of 500-1000 nm weighted to the solar spectrum (AM 1.5) increases
      almost twice: from 33% without photonic crystal to 58% with a 4 * 4 period
      superlattice photonic crystal; our result outperforms the Lambertian textured
      structure. 

PMID- 24105558
TI  - Fiber-optic multi-sensor array for detection of low concentration volatile
      organic compounds.
AB  - In this paper, we proposed a new type high sensitive volatile organic compounds
      (VOCs) gas sensor array that is based on the pulse width modulation technique.
      Four different types of solvatochromic dyes and two different types of polymers,
      were used to make the five different types of sensing membranes. These were
      deposited on the five side-polished optical fibers by a spin coater to make the
      five different sensing elements of the array. In order to ascertain the
      effectiveness of the sensors, five VOC gases were tested. Finally, principal
      component analysis (PCA) has been used to discriminates different types of VOCs. 

PMID- 24105559
TI  - Enhanced resolution in Fourier incoherent single channel holography (FISCH) with
      reduced optical path difference.
AB  - Fourier incoherent single channel holography (FISCH) is a method for recording
      spatially incoherent digital Fourier holograms. We present a general design of
      enhanced FISCH with a smaller optical path difference between interfering beams,
      when compared to our initial design [Opt. Lett. 37, 3723 (2012)]. This reduction
      enables a proper system operation with a wider bandwidth. Potential resolution
      enhancement of the images reconstructed from the FISCH holograms consequentially
      follows. 

PMID- 24105560
TI  - A novel setup for femtosecond pump-repump-probe IR spectroscopy with few cycle
      CEP stable pulses.
AB  - We present a three-color mid-IR setup for vibrational pump-repump-probe
      experiments with a temporal resolution well below 100 fs and a freely selectable
      spectral resolution of 20 to 360 cm(-1) for the pump and repump. The usable probe
      range without optical realignment is 900 cm(-1). The experimental design employed
      is greatly simplified compared to the widely used setups, highly robust and
      includes a novel means for generation of tunable few-cycle pulses with stable
      carrier-envelope phase. A Ti:sapphire pump system operating with 1 kHz and a
      modest 150 fs pulse duration supplies the total pump energy of just 0.6 mJ. The
      good signal-to-noise ratio of the setup allows the determination of spectrally
      resolved transient probe changes smaller than 6.10(-5) OD at 130 time delays in
      just 45 minutes. The performance of the spectrometer is demonstrated with
      transient IR spectra and decay curves of HDO molecules in lithium nitrate
      trihydrate and ice and a first all MIR pump-repump-probe measurement.

PMID- 24105562
TI  - High-pulse-energy, linear optical parametric oscillator with narrow and
      symmetrical far field.
AB  - A new method to obtain a narrow and symmetrical far field from a high-pulse
      energy optical parametric oscillator (OPO) with a linear resonator has been
      tested. The OPO employs two identical nonlinear crystals that are cut for type II
      phase matching, rotated such that their walk-off planes are orthogonal, and
      separated by a broadband half-wave plate. The OPO has a simple geometry, can be
      double-pass pumped, is wavelength tunable and operates stably with high
      conversion efficiency. The method has been demonstrated in a KTP-based OPO pumped
      at 1064 nm and a BBO-based OPO pumped at 532 nm, with output pulse energies up to
      60 mJ and 75 mJ, respectively. 

PMID- 24105561
TI  - Integrated micro-optical light guide plate.
AB  - In this paper, we propose an integrated micro-optical light guide plate (MOLGP),
      of which the top surface is designed as aspheric semi-cylindrical micro
      concentrator structure (ASCMCS) arrays and the bottom surface is fused with micro
      prism arrays coated with a high-reflective film. And we also present the
      optimized structural parameters and distribution pattern of the MOLGP. By the
      simulation of the professional optical software Lighttools, it's verified that
      the integrated MOLGP we proposed can achieve the functions of five complex
      structure films in current typical backlight module (BLM), and the Five
      Parameters (light energy utilization efficiency, average illuminance and
      luminance, uniformity of illuminance and uniformity of luminance) in the BLM with
      integrated MOLGP are respectively 1.49, 1.40, 1.07, 0.91 and 0.97 times than
      those in the typical BLM. Obviously, the performance parameters of the MOLGP
      exceed the traditional design. Moreover, we design two sets of four-step masks of
      the ASCMCS by the graphical user interface (GUI). At last, we fabricate a 1.8
      inch integrated MOLGP sample. Comparative experiments show that the Five
      Parameters of the fabricated MOLGP sample are respectively 1.43, 1.43, 0.97, 0.89
      and 0.70 times than those of the typical BLM. The experimental results verify the
      feasibility of the concept of the integrated MOLGP proposed in this paper. 

PMID- 24105563
TI  - Power enhancement and phase regimes in embedded microring resonators in analogy
      with electromagnetically induced transparency.
AB  - Coupled microresonators exhibit great potential for nonlinear applications. In
      the present work, we explore the nonlinear performance of an embedded ring
      resonator analogous to an electromagnetically induced transparency (EIT) medium,
      also known as coupled resonator induced transparency (CRIT). Interestingly, an
      EIT-like amplitude response can have a remarkably different power enhancement
      factor that varies by more than one order of magnitude, which is attributed to
      the different phase regimes of the embedded micro-ring resonators. In addition to
      the non-monotonic phase profile reported in atomic EIT systems, the phase
      responses featuring 2 pi and 4 pi monotonic transitions are identified and
      analyzed. We also present an interesting phenomenon, in which the power
      enhancement changes greatly, even with the same transfer function (both intensity
      and phase responses). This reveals that wisely choosing the operating regime is
      critical to optimize nonlinear performance of the embedded double resonator
      system, without adding to design or fabrication difficulty.

PMID- 24105564
TI  - Applying implicit training to polarization-division-multiplexed coherent optical
      systems.
AB  - We report the use of implicit training-aided channel estimation (ITA-CE) for
      polarization-division-multiplexed (PDM) single-carrier coherent optical systems.
      With the concept of ITA-CE, where the training sequence (TS) is arithmetically
      added onto the information symbols rather than appearing in separate time slots,
      overhead-free transmission can be achieved with minor optical signal to noise
      ratio (OSNR) penalty. ITA-CE system enables simple digital pilot-tone based
      frequency-offset compensation, and inherits the benefits from typical training
      aided channel acquisition and data recovery. Furthermore, we address the issue of
      self-interference to channel estimation (CE) of ITA-CE system in this paper. The
      data-induced interference can be eliminated by removing the cyclic mean of the
      transmitted signal, which can accelerate the convergence of the CE and allows
      smaller power to be allocated to the TS, leading to enhanced system performance.
      Numerical simulations and experiments for both PDM-QPSK and PDM-16-QAM systems
      have been conducted to verify the proposed scheme. Comparable performance to the
      conventional blind equalization system can be achieved when employing the
      transmitter side pre-distortion approach to the ITA-CE system. 

PMID- 24105565
TI  - Classifying hidden colors behind an opaque layer with the acoustically modulated
      laser speckle contrast technique.
AB  - The acoustically modulated laser speckle contrast technique has been employed to
      quantify and classify 25 colors (made up by different percentages of the two base
      colors cyan and magenta) hidden behind a 5 mm thick opaque layer with 0.24%
      transmittance. The main components included two He-Ne lasers (543 and 633 nm), a
      consumer grade digital camera (Nikon 1 J1), focusing optics and a loudspeaker.
      The camera captured the laser speckle patterns with the sound on and off,
      respectively, from which the speckle contrast differences were calculated and
      used in a nearest neighbor classification algorithm. The classification accuracy
      was between 55% and 88% depending on the underlying reflectance of all the colors
      to be classified. 

PMID- 24105566
TI  - The metal grating design of plasmonic hybrid III-V/Si evanescent lasers.
AB  - A hybrid III-V/silicon laser design with a metal grating layer inserted in
      between is proposed and numerically studied. The metal grating layer is buried in
      a silicon ridge waveguide surrounded by silicon dioxide, and its structural
      parameters such as periodicity, width and depth can be varied for optimization
      purpose. The plasmonic effect originated from the grating layer can manage
      optical fields between III-V and silicon layers in hopes of dimension reduction.
      The substrate is planarized to minimize the bonding failure. A numerical
      algorithm with various combinations of metal grating and waveguide structural
      parameters was created and the optimal design with 730 nm grating period and 600
      nm of buried waveguide ridge height was obtained by minimizing the corresponding
      laser threshold. With top AlInGaAs quantum wells and optimized design of hybrid
      metal/silicon waveguide, a 0.6 MUm(-1) threshold gain can be achieved.

PMID- 24105567
TI  - Reconfigurable add-drop multiplexer for spatial modes.
AB  - We show how a spatial mode can be extracted from a light beam, leaving the other
      orthogonal modes undisturbed, and allowing a new signal to be retransmitted on
      that mode. The method is self-aligning, avoids fundamental splitting losses, and
      uses only local feedback loops on controllable beam splitters and phase shifters.
      It could be implemented with Mach-Zehnder interferometers in planar optics. The
      method can be extended to multiple simultaneous mode extractions. As a spatial
      reconfigurable optical add-drop multiplexer, it is hitless, allowing
      reconfiguration without interrupting the transmission of any channel. 

PMID- 24105568
TI  - Generation and evolution of the terahertz vortex beam.
AB  - Based on the complementary V-shaped antenna structure, ultrathin vortex phase
      plates are designed to achieve the terahertz (THz) optical vortices with
      different topological charges. Utilizing a THz holographic imaging system, the
      two dimensional complex field information of the generated THz vortex beam with
      the topological number l=1 is directly obtained. Its far field propagation
      properties are analyzed in detail, including the rotation, the twist direction,
      and the Gouy phase shift of the vortex phase. An analytic Laguerre-Gaussian mode
      is used to simulate and explain the measured phenomena. The experimental and
      simulation results overlap each other very well. 

PMID- 24105569
TI  - Penalized maximum likelihood estimation of lifetime and amplitude images from
      multi-exponentially decaying fluorescence signals.
AB  - We investigated the penalized maximum likelihood estimation of lifetime and
      amplitude images for fluorescence lifetime imaging microscopy. The proposed
      method penalizes large variations in the lifetimes and amplitudes in the spatial
      domain to reduces noise in the images, which is a serious problem in the
      conventional maximum likelihood estimation method. For an effective optimization
      of the objective function, we applied an optimization transfer method that is
      based on a separable surrogate function. Simulations show that the proposed
      method outperforms the conventional MLE method in terms of the estimation
      accuracy, and the proposed method yielded less noisy images in real experiments. 

PMID- 24105570
TI  - Antireflective surface structures in glass by self-assembly of SiO2 nanoparticles
      and wet etching.
AB  - We describe the fabrication of an antireflective surface structure with sub
      wavelength dimensions on a glass surface using scalable low-cost techniques
      involving sol-gel coating, thermal annealing, and wet chemical etching. The glass
      surface structure consists of sand dune like protrusions with 250 nm periodicity
      and a maximum peak-to-valley height of 120 nm. The antireflective structure
      increases the transmission of the glass up to 0.9% at 700 nm, and the
      transmission remains enhanced over a wide spectral range and for a wide range of
      incident angles. Our measurements reveal a strong polarization dependence of the
      transmission change. 

PMID- 24105571
TI  - Dynamic light scattering microscope: accessing opaque samples with high spatial
      resolution.
AB  - We developed a new technique that conducts dynamic light scattering (DLS) under a
      microscope with high spatial resolution. This technique dramatically extends the
      range of DLS application from transparent to opaque samples. The total scattered
      electric field contains both electric field generated from the samples and time
      independent reflected electric field. These two components are decomposed by
      applying a partial heterodyne method. By using this technique, we successfully
      calculate the characteristic size distribution of both multiple-scattering
      samples and strong light-absorbing samples. This is the first study to observe
      the collective motion of particles in a highly concentrated solution by using
      DLS. 

PMID- 24105572
TI  - Common-path spectral interferometry with temporal carrier for highly sensitive
      surface plasmon resonance sensing.
AB  - Incorporating the temporal carrier technique with common-path spectral
      interferometry, we have successfully demonstrated an advanced surface plasmon
      resonance (SPR) biosensing system which achieves refractive index resolution
      (RIR) up to 2 * 10(-8) refractive index unit (RIU) over a wide dynamic range of 3
      * 10(-2) RIU. While this is accomplished by optimizing the SPR differential phase
      sensing conditions with just a layer of gold, we managed to address the spectral
      phase discontinuity with a novel spectral-temporal phase measurement scheme. As
      the new optical setup supersedes its Michelson counterpart in term of simplicity,
      we believe that it is a significant contribution for practical SPR sensing
      applications.

PMID- 24105573
TI  - Ultrafast all-optical modulation in a silicon nanoplasmonic resonator.
AB  - Ultrafast all-optical modulation in silicon-based metal-insulator-semiconductor
      insulator-metal nanoring resonators through photogeneration of free-carriers
      using two-photon absorption is presented 3-D through finite difference time
      domain simulations. In a compact device footprint of only 1.4 um(2), a 13.1 dB
      modulation amplitude was obtained with a switching time of only 2 ps using a
      modest pump pulse energy of 16.0 pJ. The larger bandwidth associated with more
      compact nanorings is shown to result in increased modulation amplitude.

PMID- 24105574
TI  - SiOC thin films: an efficient light source and an ideal host matrix for Eu2+
      ions.
AB  - The intense luminescence of SiOC layers is studied and its dependence on the
      parameters of the thermal annealing process elucidated. Although the emission of
      SiOC is bright enough to be interesting for practical applications, this material
      is even more promising as a host matrix for optically active Eu ions. Indeed,
      when incorporated in a SiOC matrix, Eu(3+) ions are efficiently reduced to
      Eu(2+), producing a very strong visible luminescence peaked at 440 nm. Eu(2+)
      ions benefit also of the occurrence of an energy transfer mechanism involving the
      matrix, which increases the efficiency of photon absorption for exciting
      wavelengths shorter than 300 nm. We evaluate that Eu doping of SiOC produces an
      enhancement of the luminescence intensity at 440 nm accounting for about a factor
      of 15. These properties open the way to new promising perspectives for the
      application of Eu-doped materials in photonic and lighting technologies.

PMID- 24105575
TI  - Lasing in plasmon-induced transparency nanocavity.
AB  - We propose a plasmon-induced transparency (PIT) nanocavity for achieving
      nanoscopic coherent light source. The compact cavity is constructed by a pair of
      detuned nano-stubs incorporated with four-level gain medium. The PIT response
      enables the reduction of the coupling loss from cavity to waveguide while keeping
      the cavity size unchanged, different from the end-facet Fabry-Perot cavity in
      which the radiation loss decreases at the cost of size increment. In order to
      study the lasing behavior of surface plasmon wave in the PIT cavity, the self
      consistent finite element method is employed to model the interactions between
      gain and propagating surface plasmons. The dynamics of the whole lasing process
      is observed, and the linear output-input relation is obtained for the single mode
      plasmon lasing. It is demonstrated that smaller stub-pair detuning provides
      stronger feedback inside the cavity. Consequently, the lasing threshold of
      pumping rate decreases quadratically with the decreasing of detuning. However,
      the output-input extraction efficiency will improve when the detuning is not so
      small. One of the advantages for the proposal is that the lasing output power
      from the cavity can directly couple towards the metal-dielectric-metal waveguide
      platform, facilitating the field of integrated plasmonic circuits and molecular
      scale coherent light source. 

PMID- 24105576
TI  - Optical parametric gain and bandwidth in highly nonlinear tellurite hybrid
      microstructured optical fiber with four zero-dispersion wavelengths.
AB  - The parametric amplification gain and bandwidth in highly nonlinear tellurite
      hybrid microstructured optical fiber (HMOF) are simulated based on four wave
      mixing process. The fiber core and cladding materials are made of TeO(2)-Li(2)O
      WO(3)-MoO(3)-Nb(2)O(5) and TeO(2)-ZnO-Na(2)O-P(2)O(5) glass, respectively. The
      fiber has four zero-dispersion wavelengths and the chromatic dispersion is
      flattened near the zerodispersion wavelengths. A broad gain bandwidth as wide as
      1200 nm from 1290 to 2490 nm can be realized in the near infrared window by using
      a tellurite HMOF as short as 25 cm.

PMID- 24105577
TI  - Transmission and pass-drop operations of mixed baudrate Nyquist OTDM-WDM signals
      for all-optical elastic network.
AB  - We propose the use of Nyquist OTDM-WDM signal for highly efficient, fully elastic
      all-optical networks. With the possibility of generation of ultra-coarse yet
      flexible granular channels, Nyquist OTDM-WDM can eliminate guard-bands in
      conventional WDM systems, and hence improves the spectral efficiency in network
      perspective. In this paper, transmission and pass-drop operations of mixed
      baudrate Nyquist OTDM-WDM channels from 43 Gbaud to dual-polarization 344 Gbaud
      are successfully demonstrated over 320 km fiber link with four FlexGrid
      compatible WSS nodes. A stable clock recovery is also carried out for different
      baudrate Nyquist OTDMs by optical null-header insertion technique. 

PMID- 24105578
TI  - Optical control of scattering, absorption and lineshape in nanoparticles.
AB  - We find exact conditions for the enhancement or suppression of internal and/or
      scattered fields in any smooth particle and the determination of their spatial
      distribution or angular momentum through the combination of simple fields. The
      incident fields can be generated by a single monochromatic or broad band light
      source, or by several sources, which may also be impurities embedded in the
      nanoparticle. We can design the lineshape of a particle introducing very narrow
      features in its spectral response. 

PMID- 24105579
TI  - HyDRa: control of parameters for deterministic polishing.
AB  - Deterministic hydrodynamic polishing with HyDRa requires a precise control of
      polishing parameters, such as propelling air pressure, slurry density, slurry
      flux and tool height. We describe the HyDRa polishing system and prove how
      precise, deterministic polishing can be achieved in terms of the control of these
      parameters. The polishing results of an 84 cm hyperbolic mirror are presented to
      illustrate how the stability of these parameters is important to obtain high
      quality surfaces. 

PMID- 24105580
TI  - Ergodic capacity comparison of optical wireless communications using adaptive
      transmissions.
AB  - Ergodic capacity is investigated for the optical wireless communications
      employing subcarrier intensity modulation with direct detection, and coherent
      systems with and without polarization multiplexing over the Gamma-Gamma
      turbulence channels. We consider three different adaptive transmission schemes:
      (i) variable-power, variable-rate adaptive transmission, (ii) complete channel
      inversion with fixed rate, and (iii) truncated channel inversion with fixed rate.
      For the considered systems, highly accurate series expressions for ergodic
      capacity are derived using a series expansion of the modified Bessel function and
      the Mellin transformation of the Gamma-Gamma random variable. Our asymptotic
      analysis reveals that the high SNR ergodic capacities of coherent, subcarrier
      intensity modulated, and polarization multiplexing systems gain 0.33 bits/s/Hz,
      0.66 bits/s/Hz, and 0.66 bits/s/Hz respectively with 1 dB increase of average
      transmitted optical power. Numerical results indicate that a polarization control
      error less than 10 degrees  has little influence on the capacity performance of
      polarization multiplexing systems. 

PMID- 24105581
TI  - The ratio of the kinetic inductance to the geometric inductance: a key parameter
      for the frequency tuning of the THz semiconductor split-ring resonator.
AB  - By introducing the frequency tuning sensitivity, an analytical model based on
      equivalent LC circuit is developed for the relative frequency tuning range of THz
      semiconductor split-ring resonator (SRR). And the model reveals that the relative
      tuning range is determined by the ratio of the kinetic inductance to the
      geometric inductance (RKG). The results show that under the same carrier density
      variation, a larger RKG results in a larger relative tuning range. Based on this
      model, a stacked SRR-dimer structure with larger RKG compared to the single SRR
      due to the inductive coupling is proposed, which improves the relative tuning
      range effectively. And the results obtained by the simple analytical model agree
      well with the numerical FDTD results. The presented analytical model is robust
      and can be used to analyze the relative frequency tuning of other tunable THz
      devices. 

PMID- 24105582
TI  - Error vector magnitude based parameter estimation for digital filter back
      propagation mitigating SOA distortions in 16-QAM.
AB  - We investigate the performance of digital filter back-propagation (DFBP) using
      coarse parameter estimation for mitigating SOA nonlinearity in coherent
      communication systems. We introduce a simple, low overhead method for parameter
      estimation for DFBP based on error vector magnitude (EVM) as a figure of merit.
      The bit error rate (BER) penalty achieved with this method has negligible penalty
      as compared to DFBP with fine parameter estimation. We examine different bias
      currents for two commercial SOAs used as booster amplifiers in our experiments to
      find optimum operating points and experimentally validate our method. The coarse
      parameter DFBP efficiently compensates SOA-induced nonlinearity for both SOA
      types in 80 km propagation of 16-QAM signal at 22 Gbaud. 

PMID- 24105583
TI  - Tailoring optical properties of surface charged dielectric nanoparticles based on
      an effective medium theory.
AB  - We propose an effective-medium theory (EMT) for the surface charged dielectric
      nanoparticles (CDNPs) in the long wavelength limit, in which a homogenous CDNP is
      demonstrated to be equivalent to a conventional absorbing neutral particle of the
      same size but with different constitutive parameters (effective permittivity
      epsilone and effective permeability MUe). It is found that while the surface
      charge induces negligible change of magnetic permeability in particle, it gives
      rise to a significant change of electric permittivity. The change in permittivity
      depends on the charge, the particle size, and the working frequency but is
      independent of the constituent material. In infrared frequencies, both the real
      and imaginary parts of the particle permittivity may be changed considerably by
      surface charging. At higher frequency, the surface charge can lead to a
      remarkable decrease in the real part of the permittivity while keeping its
      imaginary part nearly unchanged. Therefore, based on EMT we can tailor the
      optical properties of CDNPs by optimizing their parameters, allowing for many
      exotic phenomena, such as vanishing scattering efficiency, great enhancement of
      light absorption efficiency, and surface charge induced surface plasmon
      resonance. 

PMID- 24105584
TI  - White light conical diffraction.
AB  - Conical diffraction occurs when light is incident along the optic axis of a
      biaxial crystal. The light spreads out into a hollow cone inside the crystal,
      emerging as a hollow cylinder. The intensity distribution beyond the crystal is
      described using an adapted paraxial wave dispersion model. We show,
      experimentally and theoretically, how this results in a transition from conical
      diffraction for wavelengths at which the crystal is aligned to double refraction
      for misaligned wavelengths when using a white light source. The radius of the
      ring and location of the focal image plane (FIP) are also observed to have a
      wavelength dependency. The evolution of the conically diffracted beam beyond the
      FIP into the far field is studied and successfully described using a theoretical
      model. 

PMID- 24105585
TI  - Shear stress sensing with Bragg grating-based sensors in microstructured optical
      fibers.
AB  - We demonstrate shear stress sensing with a Bragg grating-based microstructured
      optical fiber sensor embedded in a single lap adhesive joint. We achieved an
      unprecedented shear stress sensitivity of 59.8 pm/MPa when the joint is loaded in
      tension. This corresponds to a shear strain sensitivity of 0.01 pm/uepsilon. We
      verified these results with 2D and 3D finite element modeling. A comparative FEM
      study with conventional highly birefringent side-hole and bow-tie fibers shows
      that our dedicated fiber design yields a fourfold sensitivity improvement. 

PMID- 24105586
TI  - Five-level polybinary signaling for 10 Gbps data transmission systems.
AB  - This paper presents a revitalization effort towards exploiting multilevel
      polybinary signals for spectral efficient data links. Specifically, we present
      five level polybinary signaling for 10 Gbps signals. By proper coding to avoid
      error propagation and degeneracy of the bit error rate performance, a 10 Gbps
      polybinary signal is successfully generated employing a 1.8 GHz Bessel filter
      with an electrical spectral efficiency of 5.5 bit/s/Hz. The experimental results
      show bit error rate performances below FEC level for transmission in singlemode
      and dispersion shifted fibers up to 20 km length.

PMID- 24105587
TI  - Squeezing of the mirror motion via periodic modulations in a dissipative
      optomechanical system.
AB  - We investigate the generation of squeezed state of the mirror motion in a
      dissipative optomechanical system driven with a strong laser field accompanied
      with two periodically-modulated lights. Using the density operator approach we
      calculate the variances of quantum fluctuations around the classical orbits. Both
      the numerical and analytical results predict that the squeezed state of the
      mirror motion around its ground state is achievable. Moreover, the obtained
      squeezed state is robust against the thermal noise because of the strong cooling
      effect outside the resolved-sideband regime, which arises from the destructive
      interference of quantum noise. 

PMID- 24105588
TI  - A floating type holographic display.
AB  - A floating image type holographic display which projects an electronically
      generated holographic image together with a background image displayed on a
      monitor/TV to enhance the visual effects of the former image is introduced. This
      display can display a holographic image with a spatial volume floating in the
      front space of the display with use of PDLC sheets as the focused plane of the
      image. This display can preserve and enhance the main property of holographic
      image from a display chip, i.e., a spatial image with a volume. This property had
      not been appealed by the previous holographic displays due to the much brighter
      active surface image accompanied with the reconstructed image and the diffuser
      used for viewing the image. 

PMID- 24105589
TI  - 4.5 Gbps high-speed real-time physical random bit generator.
AB  - We report a prototype of high-speed real-time physical random bit generator based
      on a chaotic laser. The chaotic laser consists of a semiconductor laser with
      optical feedback in fiber external cavity configuration. The chaotic laser
      intensity signal is quantized into binary stream by differential comparison which
      makes the amplitude distribution symmetric with respect to zero mean value. An
      exclusive-OR gate operation between two raw binary streams from the chaotic
      signal and its delayed signal is used to overcome the influences of the weak
      periodicity induced by the external cavity resonance inherent in the chaotic
      laser. After exclusive-OR operation, the prototype can generate a single fast
      random bit stream in real time without any off-line processing procedures. Its
      bit rate can be handily and continuously tuned up to 4.5 Gbps by a trigger clock.
      Experiment results demonstrate that our generator possesses high-quality
      randomness with verified by the three-standard-deviation criterion and industry
      benchmark statistical tests. 

PMID- 24105590
TI  - Straightforward method for measuring optical fiber's nonlinear coefficient based
      on phase mismatching FWM.
AB  - A novel method for measuring optical fiber's nonlinear coefficient, based on
      phase mismatching four-wave mixing is proposed. Measurements for both high
      nonlinearity dispersion shifted fiber and low nonlinearity standard single mode
      fiber are demonstrated with simple setup. Chromatic dispersion is also measured
      with high precision simultaneously, and therefore its effect to the nonlinear
      coefficient measurement can be removed. 

PMID- 24105591
TI  - Collective localized surface plasmons for high performance fluorescence
      biosensing.
AB  - Metallic nanostructures supporting collective localized surface plasmons (cLSPs)
      are investigated for the amplification of signal in fluorescence biosensors.
      cLSPs modes are supported by diffractive arrays of metallic nanoparticles that
      are embedded in a refractive index-symmetrical environment. They exhibit lower
      damping and thus their excitation is associated with higher field intensity
      enhancement and narrower resonance than that for regular localized surface
      plasmons. Through finite difference time domain (FDTD) simulations, we designed a
      novel cLSP structure that exhibit two resonances overlapping with absorption and
      emission wavelengths of assumed fluorophore (similar to Cy5 or Alexa Fluor 647).
      The simulations of surface plasmon-enhanced fluorescence (PEF) took into account
      the cLSP-driven excitation, directional emission, and mediated quantum yield in
      realistic sandwich immunoassays that utilize fluorophore-labeled detection
      antibodies. Achieved results indicate that cLSP-based structures holds potential
      for extraordinarily high fluorescence intensity enhancement that exceeds a value
      of 10(3).

PMID- 24105592
TI  - Amplification and compression of temporally shaped picosecond pulses in Yb-doped
      rod-type fibers.
AB  - We report on a new technique to produce high power sub-picosecond pulses from a
      fiber amplifier. We use parabolic pulse shaping of 27 ps transform-limited pulses
      in order to control nonlinear effects in the fiber amplifier. 63 MW, 780 fs
      pulses with 25 W average power were obtained, and ways to scale the technique to
      higher peak powers were identified.

PMID- 24105593
TI  - Spontaneous EEG fluctuations determine the readiness potential: is preconscious
      brain activation a preparation process to move?
AB  - It has been repeatedly shown that specific brain activity related to planning
      movement develops before the conscious intention to act. This empirical finding
      strongly challenges the notion of free will. Here, we demonstrate that in the
      Libet experiment, spontaneous fluctuations of the slow electro-cortical
      potentials (SCPs) account for a significant fraction of the readiness potential
      (RP). The individual potential shifts preceding self-initiated movements were
      classified as showing a negative or positive shift. The negative and positive
      potential shifts were analyzed in a self-initiated movement condition and in a no
      movement condition. Comparing the potential shifts between both conditions, we
      observed no differences in the early part of the potential. This reveals that the
      apparently negative RP emerges through an unequal ratio of negative and positive
      potential shifts. These results suggest that ongoing negative shifts of the SCPs
      facilitate self-initiated movement but are not related to processes underlying
      preparation or decision to act. 

PMID- 24105594
TI  - Coordination deficits during trunk-assisted reach-to-grasp movements in
      Parkinson's disease.
AB  - The present study investigated how Parkinson's disease (PD) affects temporal
      coordination among the trunk, arm, and fingers during trunk-assisted reach-to
      grasp movements. Seated participants with PD and healthy controls made prehensile
      movements. During the reach to the object, the involvement of the trunk was
      altered based on the instruction; the trunk was not involved, moved forward
      (flexion), or moved backward (extension) in the sagittal plane. Each of the trunk
      movements was combined with an extension or flexion motion of the arm during the
      reach. For the transport component, the individuals with PD substantially delayed
      the onset of trunk motion relative to that of arm motion in conditions where the
      trunk was moved in the direction opposite from the arm reaching toward the
      object. At the same time, variability of intervals between the onsets and
      intervals between the velocity peaks of the trunk and wrist movements was
      increased. The magnitudes of the variability measures were significantly
      correlated with the severity of PD. Regarding the grasp component, the
      individuals with PD delayed the onset of finger movements during reaching. These
      results imply that PD impairs temporal coordination between the axial and distal
      body segments during goal-directed skilled actions. When there is a directional
      discrepancy between the trunk and wrist motions, individuals with PD appear to
      prioritize wrist motion that is tied to the task goal over the trunk motion. An
      increase in disease severity magnifies the coordination deficits. 

PMID- 24105595
TI  - Multi-muscle control during bipedal stance: an EMG-EMG analysis approach.
AB  - Posture and postural reactions to mechanical perturbations require the harmonic
      modulation of the activity of multiple muscles. This precision can become
      suboptimal in the presence of neuromuscular disorders and result in higher fall
      risk and associated levels of comorbidity. This study was designed to investigate
      neurophysiological principles related to the generation and distribution of
      inputs to skeletal muscles previously recognized as a synergistic group.
      Specifically, we investigated the current hypothesis that correlated neural
      inputs, as measured by intermuscular coherence, are the mechanism used by the
      central nervous system to coordinate the formation of postural muscle synergies.
      This hypothesis was investigated by analyzing the strength and distribution of
      correlated neural inputs to postural muscles during the execution of a quiet
      stance task. Nine participants, 4 females and 5 males, mean age 29.2 years old
      (+/-6.1 SD), performed the task of standing while holding a 5-kg barbell in front
      of their bodies at chest level. Subjects were asked to maintain a standing
      position for 10 s while the activity of three postural muscles was recorded by
      surface electrodes: soleus (SOL), biceps femoris (BF), and lumbar erector spinae
      (ERE). EMG-EMG coherence was estimated for three muscle pairs (SOL/BF, SOL/ERE,
      and BF/ERE). Our choice of studying these muscles was made based on the fact that
      they have been reported as components of a functional (synergistic) muscle group
      that emerges during the execution of bipedal stance. In addition, an isometric
      contraction can be easily induced in this muscle group by simply adding a weight
      to the body's anterior aspect. The experimental condition elicited a significant
      increase in muscle activation levels for all three muscles (p < 0.01 for all
      muscles). EMG-EMG coherence analysis revealed significant coherence within two
      distinct frequency bands, 0-5 and 5-20 Hz. Significant coherence within the later
      frequency band was also found to be significantly uniformly distributed across
      the three muscle pairs. These findings are interpreted as corroborative with the
      idea of a hierarchic system of control where the controller may use the
      generation of common neural inputs to reduce the number of variables it
      manipulates.

PMID- 24105596
TI  - Effect of limb movements on orienting of attention in right-hemisphere stroke.
AB  - A deficit disengaging attention from the ipsilesional space in order to re-orient
      toward the contralesional space has been reported after right-hemisphere stroke
      (disengage deficit) and has been related to the severity of visuospatial neglect.
      Neglect rehabilitation studies have shown that left limb movements improve
      leftward orienting; the effect, however, is variable, and the mechanism of
      improvement is uncertain. Thus, this study examined whether limb movements
      specifically reduce the underlying disengage deficit of attention after right
      hemisphere stroke. The effects of active and passive limb movements (vs. no limb
      movement) on orienting were examined using a covert exogenously cued orienting
      task in groups of right-hemisphere stroke patients with and without a significant
      disengage deficit (DD+, DD-) and healthy older adults. As previously seen,
      disengage deficit scores of stroke patients were positively correlated with the
      severity of neglect. The leftward disengage deficit was not affected by either
      active or passive limb movements, however, although movements did have both
      alerting and distracting effects on other aspects of orienting. Thus, our results
      suggest that the benefits of limb movements may not be related to changes in the
      underlying disengage deficit, but may impact other processes that underlie left
      sided orienting (e.g., arousal and voluntary strategies). 

PMID- 24105597
TI  - Why does an obstacle just below the digits' paths not influence a grasping
      movement while an obstacle to the side of their paths does?
AB  - When we grasp objects in daily life, they are often surrounded by obstacles. To
      decrease the chance of colliding with an obstacle, people tend to move in a
      manner that does not bring body parts too near to the obstacle. However, in a
      previous study, when we compared moving above empty space and moving above an
      obstacle (a table), we did not find an effect of the obstacle on the height of
      the digit's paths despite the fact that the distance between the final positions
      of the digits and the obstacle was marginal. This lack of effect seems to be
      inconsistent with what we know about avoiding obstacles, because we would expect
      an increase in the height of the digits' paths when the obstacle is present. We
      consider four possible explanations for the lack of effect: that people changed
      movement speed rather than movement path, that the height component is not
      sensitive to obstacles that do not physically obstruct the movement, that
      obstacles below the starting position are not taken into account because the
      digits do not enter the space below the starting position, and that manipulable
      obstacles interfere with movement planning while a table does not. We found that
      from these four explanations only not taking obstacles placed below the starting
      position into account can be responsible for the lack of effect found in our
      previous study. 

PMID- 24105600
TI  - Chronic exposure to valproic acid promotes insulin release, reduces KATP channel
      current and does not affect Ca (2+) signaling in mouse islets.
AB  - Hyperinsulinemia is one of the reported side effects of valproic acid (VPA), a
      medicine used to treat epilepsy. However, its underlying mechanism remains
      unknown. The present study was designed to investigate a direct effect of VPA on
      insulin secretion by using mouse pancreactic islets and beta-cells. VPA had no
      acute effect on insulin secretion from islets, or on cytosolic Ca(2+) ([Ca(2+)]i)
      in single beta-cells. However, following long-term exposure to VPA (48 h), both
      basal and glucose-stimulated insulin secretion were markedly elevated (5-fold),
      while the insulin gene expression level was unaltered. Following long-term
      exposure to VPA, beta-cells showed a decrease in whole cell KATP channel current.
      However, the increase in [Ca(2+)]i in response to the sulfonylurea drug,
      tolbutamide was attenuated. The present study shows that VPA has no acute
      effects, but long-term treatment results in enhancement of both basal and glucose
      stimulated insulin secretion. This long-term effect may mediate the KATP channel,
      while VPA can also attenuate the effect of the KATP channel blocker tolbutamide. 

PMID- 24105599
TI  - Dynamics of DOT1L localization and H3K79 methylation during meiotic prophase I in
      mouse spermatocytes.
AB  - During meiotic prophase I, interactions between maternal and paternal
      chromosomes, under checkpoint surveillance, establish connections between
      homologs that promote their accurate distribution to meiotic progeny. In human,
      faulty meiosis causes aneuploidy resulting in miscarriages and genetic diseases.
      Meiotic processes occur in the context of chromatin; therefore, histone post
      translational modifications are expected to play important roles. Here, we report
      the cytological distribution of the evolutionarily conserved DOT1L
      methyltransferase and the different H3K79 methylation states resulting from its
      activity (mono-, di- and tri-methylation; H3K79me1, me2 and me3, respectively)
      during meiotic prophase I in mouse spermatocytes. In the wild type, whereas low
      amounts of H3K79me1 are rather uniformly present throughout prophase I, levels of
      DOT1L, H3K79me2 and H3K79me3 exhibit a notable increase from pachynema onwards,
      but with differential subnuclear distribution patterns. The heterochromatic
      centromeric regions and the sex body are enriched for H3K79me3. In contrast,
      H3K79me2 is present all over the chromatin, but is largely excluded from the sex
      body despite the accumulation of DOT1L. In meiosis-defective mouse mutants, the
      increase of DOT1L and H3K79me is blocked at the same stage where meiosis is
      arrested. H3K79me patterns, combined with the cytological analysis of the H3.3,
      gammaH2AX, macroH2A and H2A.Z histone variants, are consistent with a
      differential role for these epigenetic marks in male mouse meiotic prophase I. We
      propose that H3K79me2 is related to transcriptional reactivation on autosomes
      during pachynema, whereas H3K79me3 may contribute to the maintenance of
      repressive chromatin at centromeric regions and the sex body. 

PMID- 24105601
TI  - Hedgehog signaling is active in human prostate cancer stroma and regulates
      proliferation and differentiation of adjacent epithelium.
AB  - BACKGROUND: Contribution of stromal Hedgehog (Hh) signaling is evident in the
      prostate gland in mice, but needs translation to human tissues if Hh therapeutics
      are to be used effectively. Our goal was to determine if primary human prostate
      fibroblasts contain cilia, and respond to prostate Hh signaling. METHODS: Primary
      human prostate cancer-associated (CAFs), and adjacent non-malignant (NPFs)
      fibroblasts isolated from human tissue specimens were analyzed using
      immunofluorescence, real-time PCR, and available array data. Cell culture and
      tissue recombination were used to determine responsiveness of human fibroblasts
      to Hh pathway manipulation and the paracrine effects of stromal Hh signaling,
      respectively. RESULTS: Prostatic fibroblasts were capable of forming primary
      cilia, with the capacity for active Hh signaling as seen by Smo co-localization
      to the tip of the primary cilium. Expression of genes known to represent a
      signature of active Hh signaling in the prostate (especially Fgf5 and Igfbp6)
      were increased in CAFs compared to NPFs. The level of canonical Hh genes and
      prostate Hh signature genes were rarely synchronous; with lower doses of
      Purmorphamine/BMS-833923 regulating canonical transcription factors, and higher
      doses effecting prostate Hh signature genes. Grafts consisting of NPFs with
      constitutively active Hh signaling induced increased proliferation and
      dedifferentiation of adjacent non-malignant BPH-1 epithelial cells. CONCLUSIONS:
      These data show that human prostatic fibroblasts have the capacity for Hh
      signaling and manipulation. Increased expression of a signature of prostatic Hh
      genes in the prostate tumor microenvironment suggests a role in the epithelial
      transformations driving prostate cancer (PCa).

PMID- 24105602
TI  - Differences in vole preference, secondary chemistry and nutrient levels between
      naturally regenerated and planted Norway spruce seedlings.
AB  - Field voles (Microtus agrestis) cause severe damage to young Norway spruce (Picea
      abies) plantations during wintertime in Fennoscandia. We experimentally
      investigated vole preference for winter-dormant, naturally regenerated seedlings;
      spring-planted seedlings; or autumn-planted seedlings; and how preference
      corresponds with seedling chemistry. Voles showed the highest preference for
      autumn-planted seedlings and the second highest for spring-planted seedlings,
      while naturally regenerated seedlings were avoided. The stems of the autumn
      planted seedlings contained higher concentrations of nitrogen and piperidine
      alkaloids and lower concentrations of stilbenes than did the other groups. In
      addition to differences between naturally regenerated and planted seedlings, we
      investigated seasonal differences in naturally regenerated P. abies needle and
      bark secondary chemistry. While piperidine alkaloid concentrations did not vary
      with season, the soluble non-tannin phenolics of needles and the condensed
      tannins of bark were lower in May than in November or January. At the time of
      planting, the concentration of bark piperidine alkaloids was higher in autumn
      planted than in spring-planted seedlings. We detected two alkaloids not
      previously found in P. abies, 2-methyl-6-propyl-1,6-piperideine and a tentatively
      identified pinidine-isomer. Our results demonstrate that vole choice of spruce
      seedlings is promoted by high nitrogen and low stilbene content, both associated
      with seedlings planted late in the season. As vole damage is linked to seedling
      chemistry, damage potentially could be mitigated by advancing planting or by
      manipulating plant chemistry in nurseries. 

PMID- 24105603
TI  - Modulation of reproductive behaviors by non-host volatiles in the polyphagous
      Egyptian cotton leafworm, Spodoptera littoralis.
AB  - In order to locate mates, food, and oviposition sites, insects mainly rely on
      volatile cues released by their sexual partners, food sources, and host and non
      host plants. Calling, mating, and oviposition behaviors, as well as fecundity and
      longevity, of newly emerged Spodoptera littoralis (Bois.) moths were recorded in
      the presence of volatiles from leaves of a host plant, Gossypium hirsutum
      (cotton) and two non-host plants, Adhatoda vasica (Av) or Picea abies (spruce),
      either alone or in host/non-host combinations. Females exposed to cotton
      volatiles started calling earlier than females exposed to non-host plant
      volatiles (NHV), or the blank control. Likewise, moth pairs exposed to cotton
      volatiles started mating earlier than the other treatments. The period of calling
      in females alone was longer than females kept with males, having the opportunity
      to mate. However, the callings, as well as mating durations in the moth pairs, in
      different treatments were not different. Longevity was decreased either in the
      absence of cotton or the presence of Av, and spruce leaves. Fecundity was reduced
      in moths exposed to a combination of spruce and cotton. The effect of NHV on
      attraction of 2-3-day-old male moths towards a pheromone (Ph) source was studied
      in a wind tunnel. In the no-choice assay, more males arrived at close approach
      and landed on the Ph source when the host plant, cotton, was offered in the
      background as compared to the non-hosts. In the dual-choice assay, more males
      landed on the Ph source in front of the host plant compared to the Ph source in
      front of non-hosts. Gas chromatography-electroantennographic detection on female
      S. littoralis revealed five antennally active compounds in headspace collections
      of spruce and three compounds in Av. 

PMID- 24105604
TI  - A note from history: Landmarks in history of cancer, Part 6.
AB  - In the 3 decades from 1940 to 1970, the United States became the nucleus for
      research, diagnosis, and treatment of cancer. The discovery of anticancer drugs,
      and the clinical demonstration that chemotherapy and radiation can cure cancer
      and have the ability to prevent recurrence of cancer, were incontrovertibly the
      most remarkable groundbreaking events. Consequently, the trend of less surgery
      and more multimodality therapy began. The introduction of radioautography,
      mammography, ultrasonography, computed tomography, Papanicolaou smear, and other
      novel laboratory tests furthered early detection of cancer and refined accurate
      diagnosis. The unequivocal linking of lung cancer to cigarette smoking made
      medical history. The delineation of the potential role of oncogenes adduced new
      thoughts about oncogenesis and cancer prevention, and pathologists finalized the
      classification and nosology of tumors. Finally, it is worth noting that although
      more advances were made in the detection, diagnosis, and treatment of cancers
      than any other period in history, the overall mortality rate of patients with
      cancer remained high and unchanged.

PMID- 24105605
TI  - Transoral anatomy of the tonsillar fossa and lateral pharyngeal wall: anatomic
      dissection with radiographic and clinical correlation.
AB  - OBJECTIVES/HYPOTHESIS: To evaluate the transoral anatomy of the tonsillar fossa
      and lateral pharyngeal wall and to correlate these findings with radiographic
      measurements and transoral robotic surgery (TORS) of patients with early
      tonsillar tumor. STUDY DESIGN: Preclinical cadaveric study and patient cohort.
      METHODS: Six complete cadaveric dissections were performed to identify key
      anatomic landmarks, and these landmarks were validated in two consecutive
      patients with T1 human papillomavirus-positive squamous cell carcinoma of the
      tonsil treated by TORS. For radiographic landmark analysis, 25 patients who
      underwent contrast-enhanced computed tomography (CT) of the neck for a variety of
      endoscopic skull base procedures were selected. Measurements were taken from the
      lateral pharyngeal wall at C2-C3 interspace and greater horn of hyoid (C6) to the
      external carotid artery (ECA). RESULTS: The glossopharyngeal (IX) nerve was
      consistently identified deep to the superior constrictor musculature and at the
      intersection of the posterior tonsillar pillar with the base of tongue. The
      styloglossus muscle forms the deep plane medial to the ECA. The mean measurements
      for left C2-C3 interspace to the ECA and right C2-C3 interspace to ECA were 17.6
      +/- 0.8 mm and 18.4 +/- 0.8 mm, respectively. Similarly, the mean measurements
      for left hyoid to ECA and right hyoid to ECA were 3.4 +/- 0.8 mm and 4.3 +/- 0.6
      mm, respectively. CONCLUSIONS: A systematic approach to dissect the tonsillar
      fossa and lateral pharyngeal wall can be performed using key anatomic landmarks.
      CT measurements taken at the C2-C3 interspace and greater horn of hyoid bone (C6
      level) to the ECA are consistently and reliably achieved.

PMID- 24105606
TI  - Epistatic interactions and drug response.
AB  - The advent of massively parallel sequencing has allowed for an unprecedented
      genetic characterization of cancers, which has revealed not only the complexity
      of cancer genomes, but also the fact that tumours from the same anatomical site
      or even of the same histological and/or molecular subtype display distinct
      constellations of somatic genetic aberrations. Epistatic interactions (ie the
      interplay between genetic aberrations) are likely to play pivotal roles not only
      in terms of tumourigenesis and disease progression, but also in response to
      therapeutic interventions. In this review, we discuss the challenges posed by the
      complexity of tumour genomes and epistatic interactions, and approaches for
      harnessing the wealth of genetic information on human cancers for the
      implementation of precision medicine.

PMID- 24105607
TI  - Identification of 6-demethoxy-6-methylgeldanamycin and its implication of
      geldanamycin biosynthesis.

PMID- 24105608
TI  - KtzJ-dependent serine activation and O-methylation by KtzH for kutznerides
      biosynthesis.
AB  - Kutznerides are hexadepsipeptide antifungal and antimicrobial agents containing O
      methyl-L-serine in their very unique peptidic backbone. During kutznerides
      biosynthesis, this O-methylated amino-acid residue is proposed to result from the
      action of an adenylation (A) domain present in KtzH, which is interrupted by the
      S-adenosylmethionine-binding-containing part of a methyltransferase. In this
      study, we co-expressed recombinant KtzH(A4MA4T4) with its MbtH-like protein
      partner KtzJ and demonstrated the requirement for KtzJ in producing soluble and
      active KtzH(A4MA4T4). We demonstrated the specificity of KtzH(A4MA4T4) toward L
      Ser and showed the activity of the partial methyltransferase enzyme in O
      methylation of L-Ser after its covalent attachment to the thiolation domain of
      KtzH(A4MA4T4). The insights gained from this work may guide future study and
      development of engineered interrupted adenylation domains for combinatorial
      biosynthetic methodologies. 

PMID- 24105609
TI  - New doramectin analogs from mutant Streptomyces avermitilis NEAU1069-3.

PMID- 24105610
TI  - Dronabinol in severe, enduring anorexia nervosa: a randomized controlled trial.
AB  - OBJECTIVE: The evidence for pharmacological treatment of severe, longstanding
      anorexia nervosa (AN) is sparse and the few controlled pharmacologic studies have
      focused on a narrow range of drugs. The aim of the present study was to
      investigate the effects of treatment with a synthetic cannabinoid agonist on body
      weight and eating disorder-related psychopathological personality traits in women
      with severe, enduring AN. METHOD: This add-on, prospective, randomized, double
      blind, controlled crossover study was conducted between 2008 and 2011 at a
      specialized care center for eating disorders. Twenty-five women over 18 years
      with AN of at least 5 years duration were randomized to treatment with either
      dronabinol-placebo or placebo-dronabinol. In addition to the standardized
      baseline therapeutic regime, the participants received dronabinol, 2.5 mg twice
      daily for 4 weeks and matching placebo for 4 weeks, separated by a 4-week wash
      out period. Primary outcome was the mean change in body weight. Secondary outcome
      was score changes on the Eating Disorder Inventory-2 (EDI-2). Data were analyzed
      for the 24 patients who completed the trial. RESULTS: During dronabinol
      treatment, participants gained 0.73 kg (t = 2.86, df = 22, p < 0.01) above
      placebo without significant psychotropic adverse events. Dronabinol significantly
      predicted weight gain in a multiple linear regression including EDI-2 body
      dissatisfaction score and leptin. EDI-2 subscale scores showed no significant
      changes over time. DISCUSSION: Dronabinol therapy was well tolerated. During four
      weeks of exposure it induced a small but significant weight gain in the absence
      of severe adverse events.

PMID- 24105611
TI  - Protease-activated receptor 4 activation increases the expression of calcitonin
      gene-related peptide mRNA and protein in dorsal root ganglion neurons.
AB  - Accumulating evidence demonstrates that nociceptor activation evokes a rapid
      change in mRNA and protein levels of calcitonin gene-related peptide (CGRP) in
      dorsal root ganglion (DRG) neurons. Although the colocalization of CGRP and
      protease-activated receptor-4 (PAR4), a potent modulator of pain processing and
      inflammation, was detected in DRG neurons, the role of PAR4 activation in the
      expression of CGRP has not been investigated. In the present study, the
      expression of CGRP and activation (phosphorylation) of extracellular signal
      regulated kinases 1 and 2 (ERK1/2) in rat DRG neurons were measured by
      immunofluorescence, real-time PCR, and Western blotting after AYPGKF-NH2
      (selective PAR4-activating peptide; PAR4-AP) intraplantar injection or treatment
      of cultured DRG neurons. The expression of CGRP in cultured DRG neurons was also
      assessed after treatment with AYPGKF-NH2 with preaddition of PD98059 (an
      inhibitor for ERK1/2 pathway). Results showed that PAR4-AP intraplantar injection
      or treatment of cultured DRG neurons evoked significant increases in DRG cells
      displaying CGRP immunoreactivity and cytoplasmic and nuclear staining for phospho
      ERK1/2 (p-ERK1/2). Percentages of total DRG neurons expressing both CGRP and PAR4
      or p-ERK1/2 also increased significantly at 2 hr after PAR4-AP treatment. Real
      time PCR and Western blotting showed that PAR4-AP treatment significantly
      increased expression of CGRP mRNA and protein levels in DRG neurons. The PAR4
      activation-evoked CGRP expression both at mRNA and at protein levels was
      significantly inhibited after p-ERK1/2 was inhibited by PD98059. These results
      provide evidence that activation of PAR4 upregulates the expression of CGRP mRNA
      and protein levels in DRG neurons via the p-ERK1/2 signal pathway.

PMID- 24105613
TI  - Biomechanical and physiological demands of kitesurfing and epidemiology of injury
      among kitesurfers.
AB  - Kitesurfing is a relatively new extreme water sport that is considered a high
      risk sport and has rising popularity. Kitesurfing combines aspects of several
      water sports, including surfing, windsurfing, and wakeboarding. With a large
      controllable kite and a small board, kitesurfers travel over the water surface
      with speeds of up to 35 knots. The vertical lift of the kite makes it possible to
      perform jumps up to 15 m high and 30 m long, while doing different manoeuvres in
      the air. Few scientific data are available concerning the biomechanical and
      physiological demands of kitesurfing and the epidemiology of kitesurfing injury,
      and research methods used are often questionable. During kitesurfing,
      considerable stress is placed on the musculoskeletal and physiological systems,
      and the possibility of injury or fatality is an inherent part of participation.
      The lower back and thigh muscles are often perceived as being highly stressed,
      while abdominal muscles, knees, and feet are common sites of pain or discomfort.
      During kitesurfing, both aerobic and anaerobic metabolism contribute to energy
      delivery. It is reported in the literature that kitesurfing injuries are mainly
      acute, due to accidents or trauma. Non-competitive kitesurfing resulted in an
      overall injury rate of 5.9-7.0 injuries per 1,000 kitesurfing hours. It seems
      that the risk of injury increases dramatically in competitive kitesurfing.
      However, contradictory results have been found. Lower extremities were the most
      common major site of injuries, followed by upper extremities, trunk, and head.
      Most accidents during kitesurfing reported in the literature were attributed to
      the inability to detach the kite from the harness. Due to technical innovations,
      recent studies report uncontrolled actions and unsuccessful tricks and jumps with
      poor landings as the main mechanisms of injuries. The main purpose of the present
      paper is to critically analyse the current relevant scientific literature on the
      biomechanical and physiological demands of kitesurfing and the epidemiology of
      injury among kitesurfers, in order to obtain greater insights into (i) the
      stresses imposed on the musculoskeletal and physiological systems by kitesurfing,
      and (ii) the rate, pattern, and mechanisms of kitesurfing injuries.

PMID- 24105614
TI  - The role of health literacy and numeracy in contraceptive decision-making for
      urban Chicago women.
AB  - Low functional health literacy and numeracy have known associations with poor
      health outcomes, yet little work has investigated these markers of health
      disparity in a family planning population. We used an in-depth qualitative
      process and 2 literacy and numeracy assessment tools, the REALM-7 and the
      Schwartz numeracy scale, to assess the role of literacy and numeracy in
      contraceptive decision-making in an urban Chicago population. Brief surveys and
      semi-structured interviews were conducted with 30 postpartum women who had
      received Medicaid-funded care at an obstetrics clinic in an academic medical
      center. In-person one-on-one interviews were then reviewed for themes using an
      iterative process. Qualitative analysis techniques identifying emergent themes
      were applied to interview data. Literacy and numeracy were assessed using REALM-7
      and a validated 3-question numeracy scale. In this cohort of African American (63
      %) and Hispanic (37 %) women (median age 26), 73 % had unplanned pregnancies.
      Although health literacy rates on the REALM-7 were adequate, numeracy scores were
      low. Low literacy and numeracy scores were associated with interview reports of
      poor contraceptive knowledge and difficulty with contraceptive use. Low health
      literacy and numeracy may play an important role in contraception decision-making
      in this low-income, minority population of women. We recommend further study of
      literacy and numeracy in a family planning population. Comprehensive
      contraception education and communication around the contraceptive decision
      making process should take place at literacy and numeracy levels appropriate to
      each individual.

PMID- 24105615
TI  - The purinergic P2*7 receptor is expressed on monocytes in Behcet's disease and is
      modulated by TNF-alpha.
AB  - The P2*7 receptor (P2*7r) is expressed in innate immune cells (e.g.
      monocyte/macrophages), playing a key role in IL-1beta release. Since innate
      immune activation and IL-1beta release seem to be implicated in Behcet's disease
      (BD), a systemic immune-inflammatory disorder of unknown origin, we hypothesized
      that P2*7r is involved in the pathogenesis of the disease. Monocytes were
      isolated from 18 BD patients and 17 healthy matched controls. In BD monocytes, an
      increased P2*7r expression and Ca(2+) permeability induced by the selective P2*7r
      agonist 2'-3'-O-(4-benzoylbenzoyl)ATP (BzATP) was observed. Moreover, IL-1beta
      release from LPS-primed monocytes stimulated with BzATP was markedly higher in BD
      patients than in controls. TNF-alpha-incubated monocytes from healthy subjects
      almost reproduced the findings observed in BD patients, as demonstrated by the
      increase in P2*7r expression and BzATP-induced Ca(2+) intake. Our results provide
      evidence that in BD monocytes both the expression and function of the P2*7r are
      increased compared with healthy controls, as the possible result, at least in
      part, of a positive modulating effect of TNF-alpha on the receptor. These data
      indicate P2*7r as a new potential therapeutic target for the control of BD,
      further supporting the rationale for the use of anti-TNF-alpha drugs in the
      treatment of the disease. 

PMID- 24105612
TI  - The incidence and prevalence of ankle sprain injury: a systematic review and meta
      analysis of prospective epidemiological studies.
AB  - BACKGROUND: Ankle sprain is one of the most common musculoskeletal injuries, yet
      a contemporary review and meta-analysis of prospective epidemiological studies
      investigating ankle sprain does not exist. OBJECTIVE: Our aim is to provide an up
      to-date account of the incidence rate and prevalence period of ankle sprain
      injury unlimited by timeframe or context activity. METHODS: We conducted a
      systematic review and meta-analyses of English articles using relevant
      computerised databases. Search terms included Medical Search Headings for the
      ankle joint, injury and epidemiology. The following inclusion criteria were used:
      the study must report epidemiology findings of injuries sustained in an observed
      sample; the study must report ankle sprain injury with either incidence rate or
      prevalence period among the surveyed sample, or provide sufficient data from
      which these figures could be calculated; the study design must be prospective.
      Independent extraction of articles was performed by two authors using pre
      determined data fields. RESULTS: One-hundred and eighty-one prospective
      epidemiology studies from 144 separate papers were included. The average rating
      of all the included studies was 6.67/11, based on an adapted version of the
      STROBE (STrengthening the Reporting of OBservational studies in Epidemiology)
      guidelines for rating observational studies. 116 studies were considered high
      quality and 65 were considered low quality. The main findings of the meta
      analysis demonstrated a higher incidence of ankle sprain in females compared with
      males (13.6 vs 6.94 per 1,000 exposures), in children compared with adolescents
      (2.85 vs 1.94 per 1,000 exposures) and adolescents compared with adults (1.94 vs
      0.72 per 1,000 exposures). The sport category with the highest incidence of ankle
      sprain was indoor/court sports, with a cumulative incidence rate of 7 per 1,000
      exposures or 1.37 per 1,000 athlete exposures and 4.9 per 1,000 h. Low-quality
      studies tended to underestimate the incidence of ankle sprain when compared with
      high-quality studies (0.54 vs 11.55 per 1,000 exposures). Ankle sprain prevalence
      period estimates were similar across sub-groups. Lateral ankle sprain was the
      most commonly observed type of ankle sprain. CONCLUSIONS: Females were at a
      higher risk of sustaining an ankle sprain compared with males and children
      compared with adolescents and adults, with indoor and court sports the highest
      risk activity. Studies at a greater risk of bias were more likely to
      underestimate the risk of ankle sprain. Participants were at a significantly
      higher risk of sustaining a lateral ankle sprain compared with syndesmotic and
      medial ankle sprains.

PMID- 24105617
TI  - Psychosocial outcome in cardiovascular rehabilitation of peripheral artery
      disease and coronary artery disease patients.
AB  - We investigated patients with a primary diagnosis of peripheral artery disease (n
      = 69) and coronary heart disease (CAD; n = 520) at baseline and on changes in
      psychosocial risk factors (depression, anxiety, quality of life, negative and
      positive affect) during a cardiovascular rehabilitation program. Patients
      completed psychosocial questionnaires at the beginning and at discharge of a 12
      week rehabilitation program. Depression and anxiety were measured with the
      Hospital Anxiety and Depression Scale (HADS), positive and negative affect with
      the Global Mood Scale, and health-related quality of life with the SF-36 Health
      Survey. Patients with PAD showed improvements in anxiety (p < 0.001), negative
      affect (p < 0.001) and bodily pain (p < 0.001). Patients with CAD reported
      significant improvements in all measured dimensions (all p-values < 0.001). 

PMID- 24105616
TI  - Barriers to screening and diagnosis of peripheral artery disease by general
      practitioners.
AB  - Peripheral artery disease (PAD) is a strong predictor of cardiovascular morbidity
      and mortality yet it is under-recognised and undertreated. General practitioners
      (GPs) are best positioned to detect patients with PAD. This article investigates
      awareness of PAD by GPs; the prevalence of screening for PAD and tools used for
      screening and diagnosis, in particular the ankle-brachial index (ABI); and the
      barriers to PAD screening and measurement of the ABI in the general practice
      setting. A cross-sectional survey of primary care practitioners was conducted
      between September 2011 and March 2012. A mail-out survey was distributed to 1120
      GPs practising in Queensland, Australia: 287 (26%) responded; 61% of GPs reported
      screening for PAD; 58% of GPs reported 'never' measuring the ABI; and 70%
      reported using arterial duplex ultrasound as their first-line diagnostic tool.
      Equipment availability, time constraints and lack of training and skills were
      identified as the most significant barriers to screening and ABI testing. In
      conclusion, there are deficits in the utilisation of guideline recommendations
      relating to PAD screening and diagnosis by Australian GPs. Our data suggest that
      earlier detection of PAD may be achieved through GP education combined with
      increased access to ABI equipment or the availability of a more time-efficient
      test. 

PMID- 24105618
TI  - Molecular modeling for Cu(II)-aminopolycarboxylate complexes: structures,
      conformational energies, and ligand binding affinities.
AB  - A ligand field molecular mechanics (LFMM) force field (FF) has been developed for
      d(9) copper(II) complexes of aminopolycarboxylate ligands. Training data were
      derived from density functional theory (DFT) geometry optimizations of 14
      complexes comprising potentially hexadentate N2O4, tetrasubstituted
      ethylenediamine (ed), and propylenediamine cores with various combinations of
      acetate and propionate side arms. The FF was validated against 13 experimental
      structures from X-ray crystallography including hexadentate N2O4 donors where the
      nitrogens donors are forced to be cis and bis-tridentate ONO ligands which
      generate complexes with trans nitrogen donors. Stochastic conformational searches
      for [Cu{ed(acetate)n(propionate)(4-n)}](2-), n = 0-4, were carried out and the
      lowest conformers for each system reoptimized with DFT. In each case, both DFT
      and LFMM predict the same lowest-energy conformer and the structures and energies
      of the higher-energy conformers are also in satisfactory agreement. The relative
      interaction energies for n = 0, 2, and 4 computed by molecular mechanics
      correlate with the experimental log beta binding affinities. Adding in the
      predicted log beta values for n = 1 and 3 suggest for this set of complexes a
      monotonic decrease in log beta as the number of propionate arms increases.

PMID- 24105619
TI  - Expression of DIAPH1 is up-regulated in colorectal cancer and its down-regulation
      strongly reduces the metastatic capacity of colon carcinoma cells.
AB  - In most cases, metastatic colorectal cancer is not curable, thus new approaches
      are necessary to identify novel targets for colorectal cancer therapy. Actin
      binding-proteins (ABPs) directly regulate motility of metastasising tumor cells,
      and for cortactin an association with colon cancer metastasis has been already
      shown. However, as its depletion only incompletely inhibits metastasis,
      additional, more suitable cellular targets have to be identified. Here we
      analyzed expression of the ABPs, DIAPH1, VASP, N-WASP, and fascin in comparison
      with cortactin and found that, besides cortactin, DIAPH1 was expressed with the
      highest frequency (63%) in colorectal cancer. As well as cortactin, DIAPH1 was
      not detectable in normal colon tissue and expression of both proteins was
      positively correlated with metastasis of colorectal cancer. To analyse the
      mechanistic role of DIAPH1 for metastasis of colon carcinoma cells in comparison
      with cortactin, expression of the proteins was stably down-regulated in the human
      colon carcinoma cell lines HT-29, HROC-24 and HCT-116. Analysis of metastasis of
      colon carcinoma cells in SCID mice revealed that depletion of DIAPH1 reduced
      metastasis 60-fold and depletion of cortactin 16-fold as compared with control
      cells. Most likely the stronger effect of DIAPH1 depletion on colon cancer
      metastasis is due to the fact that in vitro knock down of DIAPH1 impaired all
      steps of metastasis; adhesion, invasion and migration while down-regulation of
      cortactin only reduced adhesion and invasion. This very strong reducing effect of
      DIAPH1 depletion on colon carcinoma cell metastasis makes the protein a promising
      therapeutic target for individualized colorectal cancer therapy. 

PMID- 24105620
TI  - The electrophysiological principles of the electrical stimulation test in the
      epidural compartment.

PMID- 24105621
TI  - Exploring glyoxalase 1 expression in prostate cancer tissues: targeting the
      enzyme by ethyl pyruvate defangs some malignancy-associated properties.
AB  - BACKGROUND: The glyoxalase (GLO)1 is part of a ubiquitous detoxification system
      in the glycolytic pathway of normal and tumor cells. It protects against cellular
      damage caused by cytotoxic metabolites. METHODS: Aiming at exploring the role of
      GLO1 in prostate cancer, we evaluated and targeted the expression of GLO1 in
      prostate cancer tissues and cell lines and analyzed its correlation with grading
      systems and tumor growth indices. RESULTS: Immunohistochemical studies on 37
      prostate cancer specimens revealed a positive correlation between Helpap-grading
      and the cytoplasmic (P = 0.002)/nuclear (P = 0.006) GLO1 level. A positive
      correlation between Ki-67 proliferation marker and the cytoplasmic GLO1 (P =
      0.006) was evident. Furthermore, the highest GLO1 level was detected in the
      androgen-sensitive LNCaP compared to the androgen-independent Du-145 and PC-3
      prostate cell lines and the breast cancer cell MCF-7, both at protein and mRNA
      level. Treating cancer cells with ethyl pyruvate was found to defang some
      malignancy-associated properties of cancer cells including proliferation,
      invasion and anchorage-independent growth. In vitro results revealed that the
      potency of ethyl pyruvate is increased when cells are metabolically activated by
      growth stimulators, for example, by fetal calf serum, dihydrotestosterone, tumor
      growth factor-beta1 and leptin. CONCLUSIONS: The positive correlation of GLO1
      expression level in prostate cancer tissues with the pathological grade and
      proliferation rate may assign GLO1 as a risk factor for prostate cancer
      development and progression. Furthermore, our data indicate that inhibitors of
      GLO1 might be useful to decelerate the cancer cell growth by a novel therapeutic
      approach that we may call "induced metabolic catastrophe."

PMID- 24105622
TI  - Mediterranean diet and cardiovascular disease: historical perspective and latest
      evidence.
AB  - The concept that the Mediterranean diet was associated with a lower incidence of
      cardiovascular disease (CVD) was first proposed in the 1950s. Since then, there
      have been randomized controlled trials and large epidemiological studies that
      reported associations with lower CVD: in 1994 and 1999, the reports of the
      intermediate and final analyses of the trial Lyon Diet Heart Study; in 2003, a
      major epidemiological study in Greece showing a strong inverse association
      between a Mediterranean score and the risk of cardiovascular complications; in
      2011-2012, several reports showing that even non-Mediterranean populations can
      gain benefits from long-term adhesion to the Mediterranean diet; and in 2013, the
      PREDIMED trial showing a significant risk reduction in a low-risk population.
      Contrary to the pharmacological approach of cardiovascular prevention, the
      adoption of the Mediterranean diet has been associated with a significant
      reduction in new cancers and overall mortality. Thus, in terms of evidence-based
      medicine, the full adoption of a modern version of the Mediterranean diet pattern
      can be considered one of the most effective approaches for the prevention of
      fatal and nonfatal CVD complications. 

PMID- 24105623
TI  - Length of time from extubation to cardiorespiratory death in neonatal intensive
      care patients and assessment of suitability for organ donation.
AB  - OBJECTIVE: A common concern for parents when end of life decisions are made is
      the length of time their baby may take to die. Postcardiac death organ donation
      is now becoming more common, along with neonatal organ donation. The aim was to
      determine the length of time from extubation until cardiorespiratory death (CRD)
      in neonatal intensive care patients and consideration of potential organ
      donation. DESIGN: Retrospective review of medical records of neonates who died in
      a neonatal intensive care unit between 2000 and 2009. PATIENTS: Data collected
      included gestation at birth, age at death, birth weight, reason for cessation of
      intensive care, inotrope and ventilation requirements, sedation and muscle
      relaxation prior to death, time from extubation to documented CRD. An assessment
      was made for potential suitability for consideration of organ donation with a
      gestation at birth >= 34 weeks and birth weight >2.0 kg. RESULTS: 117 neonates
      were included, median gestation 29 weeks and median birth weight 1220 grams. The
      median age at death was 4 days of age. The median time from discussing prognosis
      to death was 137 min. The median time from extubation to CRD was 30 min. Seven
      (6%) neonates were considered suitable for organ donation, and for these infants
      the median time from extubation to CRD was 120 min. Two neonates donated heart
      valves. CONCLUSIONS: This provides a guide for grieving parents on time frames
      for the interval between extubation and CRD. More accurate postextubation CRD
      times are required to determine likely potential for postcardiac death organ
      donation.

PMID- 24105624
TI  - A systematic review of thyroid dysfunction in preterm neonates exposed to topical
      iodine.
AB  - OBJECTIVE: To determine whether maternal exposure to iodine or neonatal exposure
      to topical iodine-containing solutions increases the risk of transient thyroid
      dysfunction in neonates born <32 weeks' gestation or <1.5 kg. DESIGN: Systematic
      review. SEARCH STRATEGY: Electronic searches were conducted using Medline and the
      Cochrane Library. ELIGIBILITY CRITERIA: A study was eligible for review if it
      reported neonatal exposure to topical iodine or maternal iodine exposure. The key
      outcome measure was neonatal thyroid function. The search had no restrictions on
      date of publication, type of study or language. RESULTS: 794 papers were
      identified during the initial search; 15 studies were fully reviewed. The
      incidence of (transient) hypothyroidism/hyperthyrotropinaemia following exposure
      to topical iodine ranged from 12 to 33 per 100 infants; the incidence in non
      exposed infants was 0. CONCLUSIONS: There is evidence that neonatal exposure to
      iodine-containing disinfectants causes thyroid dysfunction in infants born <32
      weeks. None of the studies evaluated neurodevelopment. Larger scale studies are
      needed to determine definitively the nature of the relationship and the impact of
      exposure on neurodevelopment. In the meantime, it would seem prudent to restrict
      exposure of iodine-containing skin disinfectants in preterm infants;
      chlorhexidine might be a credible alternative.

PMID- 24105625
TI  - Sources of variation in primary care clinical workflow: implications for the
      design of cognitive support.
AB  - This article identifies sources of variation in clinical workflow and
      implications for the design and implementation of electronic clinical decision
      support. Sources of variation in workflow were identified via rapid ethnographic
      observation, focus groups, and interviews across a total of eight medical centers
      in both the Veterans Health Administration and academic medical centers
      nationally regarded as leaders in developing and using clinical decision support.
      Data were reviewed for types of variability within the social and technical
      subsystems and the external environment as described in the sociotechnical
      systems theory. Two researchers independently identified examples of variation
      and their sources, and then met with each other to discuss them until consensus
      was reached. Sources of variation were categorized as environmental (clinic
      staffing and clinic pace), social (perception of health information technology
      and real-time use with patients), or technical (computer access and information
      access). Examples of sources of variation within each of the categories are
      described and discussed in terms of impact on clinical workflow. As technologies
      are implemented, barriers to use become visible over time as users struggle to
      adapt workflow and work practices to accommodate new technologies. Each source of
      variability identified has implications for the effective design and
      implementation of useful health information technology. Accommodating moderate
      variability in workflow is anticipated to avoid brittle and inflexible workflow
      designs, while also avoiding unnecessary complexity for implementers and users. 

PMID- 24105626
TI  - Recent reports of Wi-Fi and mobile phone-induced radiation on oxidative stress
      and reproductive signaling pathways in females and males.
AB  - Environmental exposure to electromagnetic radiation (EMR) has been increasing
      with the increasing demand for communication devices. The aim of the study was to
      discuss the mechanisms and risk factors of EMR changes on reproductive functions
      and membrane oxidative biology in females and males. It was reported that even
      chronic exposure to EMR did not increase the risk of reproductive functions such
      as increased levels of neoantigens abort. However, the results of some studies
      indicate that EMR induced endometriosis and inflammation and decreased the number
      of follicles in the ovarium or uterus of rats. In studies with male rats,
      exposure caused degeneration in the seminiferous tubules, reduction in the number
      of Leydig cells and testosterone production as well as increases in luteinizing
      hormone levels and apoptotic cells. In some cases of male and female infertility,
      increased levels of oxidative stress and lipid peroxidation and decreased values
      of antioxidants such as melatonin, vitamin E and glutathione peroxidase were
      reported in animals exposed to EMR. In conclusion, the results of current studies
      indicate that oxidative stress from exposure to Wi-Fi and mobile phone-induced
      EMR is a significant mechanism affecting female and male reproductive systems.
      However, there is no evidence to this date to support an increased risk of female
      and male infertility related to EMR exposure. 

PMID- 24105627
TI  - Surface charges of the membrane crucially affect regulation of Na,K-ATPase by
      phospholemman (FXYD1).
AB  - The human alpha1/His10-beta1 isoform of Na,K-ATPase has been reconstituted as a
      complex with and without FXYD1 into proteoliposomes of various lipid compositions
      in order to study the effect of the regulatory subunit on the half-saturating Na+
      concentration (K(1/2)) of Na+ ions for activation of the ion pump. It has been
      shown that the fraction of negatively charged lipid in the bilayer crucially
      affects the regulatory properties. At low concentrations of the negatively
      charged lipid DOPS (<10 %), FXYD1 increases K(1/2) of Na+ ions for activation of
      the ion pump. Phosphorylation of FXYD1 by protein kinase A at Ser68 abrogates
      this effect. Conversely, for proteoliposomes made with high concentrations of
      DOPS (>10 %), little or no effect of FXYD1 on the K(1/2) of Na+ ions is observed.
      Depending on ionic strength and lipid composition of the proteoliposomes, FXYD1
      can alter the K(1/2) of Na+ ions by up to twofold. We propose possible molecular
      mechanisms to explain the regulatory effects of FXYD1 and the influence of
      charged lipid and protein phosphorylation. In particular, the positively charged
      C-terminal helix of FXYD1 appears to be highly mobile and may interact with the
      cytoplasmic N domain of the alpha-subunit, the interaction being strongly
      affected by phosphorylation at Ser68 and the surface charge of the membrane.

PMID- 24105628
TI  - Effect of prediabetes on membrane bicarbonate transporters in testis and
      epididymis.
AB  - The formation of competent spermatozoa is a complex event that depends on the
      establishment of adequate environments throughout the male reproductive tract.
      This includes the control of bicarbonate (HCO3-) concentration, which plays an
      essential role in the maintenance of extracellular and intracellular pH (pH(i))
      values. Diabetes mellitus alters pHi regulation in mammalian cells, mainly by
      altering the activity of ion transporters, particularly HCO3--dependent
      mechanisms. Yet, little is known about the effects of this pathology and its
      prodromal stage, prediabetes, on the membrane transport mechanisms of male
      reproductive tract cells. Herein, we analyzed protein and mRNA levels of the most
      relevant HCO3- transporters of the SLC4 family [anion exchanger 2 (AE2), Na+
      driven Cl-/HCO3- exchanger (NDCBE), electrogenic Na+/HCO3- cotransporter 1
      (NBCe1), electroneutral Na+/HCO3- cotransporter 1 (NBCn1)] in the testis and
      epididymis of a prediabetic animal model. Firstly, we identified the HCO3-
      transporters of the SLC4 family, in both testicular and epididymal tissue.
      Secondly, although no alterations were detected in protein expression, mRNA
      levels of NBCe1, NBCn1 and NDCBE were significantly increased in the testis of
      prediabetic rats. On the other hand, in the epididymis, prediabetes caused an
      increase of AE2 and a decrease of NDCBE protein levels. These alterations may be
      translated into changes of HCO3- transepithelial epididymal fluxes in vivo, which
      may represent a threat for sperm survival. Moreover, these results provide
      evidence of the molecular mechanism that may be responsible for the significant
      increase in abnormal sperm morphology already reported in prediabetic rats.

PMID- 24105629
TI  - Desquamation is a novel phenomenon for collective prostate epithelial cell
      deletion after castration.
AB  - The mechanism underlying castration-induced prostate regression, which is a
      classical physiological concept translated into the therapeutic treatment of
      advanced prostate cancer, involves epithelial cell apoptosis. In searching for
      events and mechanisms contributing to prostate regression in response to androgen
      modulation, we have frequently observed the collective deletion of epithelial
      cells. This work was undertaken to characterize this phenomenon hereafter named
      desquamation and to verify its presence after 17beta-estradiol (E2)
      administration. Electron microscopy revealed that the desquamating cells had
      preserved cell-cell junctions and collapsed nuclear contents. The TUNEL reaction
      was negative for these cells, which were also negative for cleaved caspases-8, 
      9, -3 and nuclear apoptosis-inducing factor. Detailed analyses revealed that the
      condensed chromatin was first affected detaching from the nuclear lamina, which
      was observable after lamin A immunohistochemistry, suggesting the lack of lamin A
      degradation. A search in animals treated with supraphysiological E2 employed as
      an alternative anti-androgen treatment revealed no desquamation. The combined
      treatment (Cas + E2 group) caused changes particular to each treatment, including
      desquamation. In conclusion, desquamation appeared as a novel phenomenon
      contributing to collective prostate epithelial cell deletion, distinct from the
      classical castration-induced apoptosis and particular to the androgen deprivation
      resulting from surgical castration, and should be considered as part of the
      mechanisms promoting organ regression. 

PMID- 24105630
TI  - Cost effectiveness of proton therapy compared with photon therapy in the
      management of pediatric medulloblastoma.
AB  - BACKGROUND: Proton therapy has been a hotly contested issue in both scientific
      publications and lay media. Proponents cite the modality's ability to spare
      healthy tissue, but critics claim the benefit gained from its use does not
      validate its cost compared with photon therapy. The objective of this study was
      to evaluate the cost effectiveness of proton therapy versus photon therapy in the
      management of pediatric medulloblastoma. METHODS: A cost-effective analysis was
      performed from the societal perspective using a Monte Carlo simulation model. A
      population of pediatric medulloblastoma survivors aged 18 years was studied who
      had received treatment at age 5 years and who were at risk of developing 10
      adverse events, such as growth hormone deficiency, coronary artery disease,
      ototoxicity, secondary malignant neoplasm, and death. Costing data included the
      cost of investment and the costs of diagnosis and management of adverse health
      states from institutional and Medicare data. Longitudinal outcomes data and
      recent modeling studies informed risk parameters for the model. Incremental cost
      effectiveness ratios were used to measure outcomes. RESULTS: Results from the
      base case demonstrated that proton therapy was associated with higher quality
      adjusted life years and lower costs; therefore, it dominated photon therapy. In 1
      way sensitivity analyses, proton therapy remained the more attractive strategy,
      either dominating photon therapy or having a very low cost per quality-adjust
      life year gained. Probabilistic sensitivity analysis illustrated the domination
      of proton therapy over photon therapy in 96.4% of simulations. CONCLUSIONS: By
      using current risk estimates and data on required capital investments, the
      current study indicated that proton therapy is a cost-effective strategy for the
      management of pediatric patients with medulloblastoma compared with standard of
      care photon therapy.

PMID- 24105631
TI  - Drinking or not drinking in pregnancy: the multiplicity of confounding
      influences.
AB  - AIMS: Studies investigating associations between prenatal exposure to low
      moderate doses of alcohol and mental health development in childhood are
      inconsistent. The aim of the present study was to compare women who drink and who
      do not drink alcohol in pregnancy on a number of potential confounding variables,
      and to investigate whether any latent variables could be identified among these.
      METHODS: Data were obtained from the Danish National Birth Cohort. EXPOSURE:
      cumulated alcohol intake in full pregnancy (n = 63,464). The women were
      subdivided into intake groups 0, >0-10, >10-30, >30-90 and >90 units of alcohol
      in full pregnancy. Hereafter, the abstainers were subdivided into an all-time and
      a pregnancy-abstaining group, and the high intakers (>90) were subdivided into a
      high (>90-180) and a very high (>180) intake group. OUTCOME: self-reported and
      register-based information on socio-demographic and lifestyle factors, and latent
      variables from an exploratory factor analysis. RESULTS: Significant differences
      were observed between the intake groups on virtually all parameters. Significant
      differences were observed between the abstaining groups and the high-intake
      groups. The exploratory factor analyses identified a number of latent variables
      between the potential confounding variables. CONCLUSION: Differences on
      confounding factors may in part explain the lack of consistency in the literature
      investigating prenatal exposure to low-moderate doses of alcohol and mental
      health development. It is cautiously concluded that the failure to control for
      these factors introduces residual and/or unmeasured confounding into the
      analyses, and thus masks the potential (small) effect of being exposed to low
      doses of alcohol in pregnancy. It is recommended that future studies control for
      factor scores rather than for the observed variables as is practice today.

PMID- 24105632
TI  - Virtual surgical planning in endoscopic skull base surgery.
AB  - OBJECTIVES/HYPOTHESIS: Skull base surgery (SBS) involves operative tasks in close
      proximity to critical structures in a complex three-dimensional (3D) anatomy. The
      aim was to investigate the value of virtual planning (VP) based on preoperative
      magnetic resonance imaging (MRI) for surgical planning in SBS and to compare the
      effects of virtual planning with 3D contours between the expert and the surgeon
      in training. STUDY DESIGN: Retrospective analysis. METHODS: Twelve patients with
      manually segmented anatomical structures based on preoperative MRI were evaluated
      by eight surgeons in a randomized order using a validated National Aeronautics
      and Space Administration Task Load Index (NASA-TLX) questionnaire. RESULTS:
      Multivariate analysis revealed significant reduction of workload when using VP
      (P<.0001) compared to standard planning. Further, it showed that the experience
      level of the surgeon had a significant effect on the NASA-TLX differences
      (P<.05). Additional subanalysis did not reveal any significant findings regarding
      which type of surgeon benefits the most (P>.05). CONCLUSIONS: Preoperative
      anatomical segmentation with virtual surgical planning using contours in
      endoscopic SBS significantly reduces the workload for the expert and the surgeon
      in training.

PMID- 24105633
TI  - Mechanisms of age-related macular degeneration and therapeutic opportunities.
AB  - As the age of the population increases in many nations, age-related degenerative
      diseases pose significant socioeconomic challenges. One of the key degenerative
      diseases that compromise quality of life is age-related macular degeneration
      (AMD). AMD is a multi-faceted condition that affects the central retina, which
      ultimately leads to blindness in millions of people worldwide. The
      pathophysiology and risk factors for AMD are complex, and the symptoms manifest
      in multiple related but distinct forms. The ability to develop effective
      treatments for AMD will depend on a thorough understanding of the underlying
      pathophysiology, risk factors, and driver molecular pathways, as well as the
      ability to develop useful animal models. This review provides an overview of the
      aforementioned aspects in AMD.

PMID- 24105634
TI  - Nuclear factor-kappaB/Bcl-XL pathway is involved in the protective effect of
      hydrogen-rich saline on the brain following experimental subarachnoid hemorrhage
      in rabbits.
AB  - Early brain injury (EBI), a significant contributor to poor outcome after
      subarachnoid hemorrhage (SAH), is intimately associated with neuronal apoptosis.
      Recently, the protective role of hydrogen (H2 ) in the brain has been widely
      studied, but the underlying mechanism remains elusive. Numerous studies have
      shown nuclear factor-kappaB (NF-kappaB) as a crucial survival pathway in neurons.
      Here we investigated the role of H2 in EBI following SAH, focusing on the NF
      kappaB pathway. A double blood injection model was used to produce experimental
      SAH, and H2 -rich saline was injected intraperitoneally. NF-kappaB activity
      within the occipital cortex was measured. Immunofluorescence was performed to
      demonstrate the activation of NF-kappaB; Bcl-xL and cleaved caspase-3 were
      determined via Western blot. Gene expression of Bcl-xL was detected by real-time
      PCR, and TUNEL and Nissl staining were performed to illustrate brain injury in
      the occipital cortex. SAH induced a significant increase of cleaved caspase-3.
      Correspondingly, TUNEL staining demonstrated obvious neuronal apoptosis following
      SAH. In contrast, H2 treatment markedly increased NF-kappaB activity and the
      expression of Bcl-xL and decreased the level of cleaved caspase-3. Additionally,
      H2 treatment significantly reduced post-SAH neuronal apoptosis. The current study
      shows that H2 treatment alleviates EBI in the rabbits following SAH and that NF
      kappaB/Bcl-xL pathway is involved in the protective role of H2 .

PMID- 24105636
TI  - An in vitro study on focusing fs-laser pulses into ocular media for ophthalmic
      surgery.
AB  - BACKGROUND AND OBJECTIVE: To investigate femtosecond (fs)-laser patterns within
      ocular media for ophthalmic surgery. METHODS: Vitreous and crystalline lens
      tissue from porcine eyes were treated with 2-dimensional fs-laser patterns and
      inspected under the optical microscope. Time resolved pump-probe experiments were
      conducted on vitreous tissue and gelatin, which should act as a model for
      crystalline lens tissue. RESULTS: Within crystalline lens tissue, pulse overlap
      leads to the formation of large bubbles, which is caused by subsequent energy
      input from the surrounding plasma channel. This effect can be used for bubble
      size control. Vitreous tissue behaves similar to water under fs-laser treatment,
      but it still allows fs-laser cutting. CONCLUSION: Bubble size control by laser
      bursts may reduce optical side-effects of fs-laser treatment. Furthermore, fs
      laser treatment could be used for vitreoretinal applications.

PMID- 24105635
TI  - Expression of an anti-RNA autoantibody in a mouse model of SLE increases
      neutrophil and monocyte numbers as well as IFN-I expression.
AB  - Systemic lupus erythematosus (SLE) is an autoimmune disease characterized by the
      presence of antinucleic acid autoantibodies, high levels of circulating type I
      interferon (IFN-I), and an IFN-I-dependent elevated expression of activating
      FcgammaR. Increases in neutrophils and monocytes are often observed in clinical
      SLE, but how these contribute to autoantibody and IFN-I production is poorly
      understood. Here, we analyzed SLE pathogenesis in 564Igi mice, an SLE-model
      strain carrying gene-targeted heavy and light chain antibody genes encoding an
      anti-RNA autoantibody in a C57BL/6 background. Similar to human SLE patients,
      564Igi mice produce anti-RNA autoantibodies and expanded neutrophil and monocyte
      populations. These myeloid cells produced IFN-I and exhibit increased FcgammaRIV
      expression induced via an IFN-I autocrine loop. A direct effect of IFN-I on 56
      Igi BM B cells and neutrophils was supported by their upregulation of "IFN-I
      signature genes". In addition, 564Igi developing B cells showed upregulated TLR7
      resulting in IgG2a/2b class switch recombination and autoantibody production. Our
      results indicate that the production of anti-RNA autoantibody is sufficient to
      induce an increase of BM, blood, and spleen IFN-I-producing neutrophils, and
      suggest a mechanism by which autoantibody and IFN-I contribute to SLE by
      activating B lymphocytes, neutrophils, and monocyte effector cells in vivo.

PMID- 24105637
TI  - Anxiety-increasing effects of mindful eating exercises may be of benefit--comment
      on Marek et al. (2013).

PMID- 24105638
TI  - Combination of sunitinib with anti-tumor vaccination inhibits T cell priming and
      requires careful scheduling to achieve productive immunotherapy.
AB  - Sunitinib, a protein tyrosine kinase inhibitor is the frontline therapy for renal
      and gastrointestinal cancers. We hypothesized that by virtue of its well
      documented tumor apoptosis and immune adjuvant properties, combination of
      Sunitinib with anti-tumor immunotherapeutics will provide synergistic inhibition
      of tumor growth. Our study was designed to evaluate the impact of Sunitinib on
      immunotherapy mediated anti-tumor immune responses and evaluate its efficacy as a
      combinatorial therapy with tumor targeted immunotherapeutic vaccination. Mice
      immunized with recombinant alpha-lactalbumin, a lactation protein expressed on
      majority of breast tumors were treated with 1 mg of Sunitinib for seven
      consecutive days beginning (1) concurrently, on the day of alpha-lactalbumin
      immunization or (2) sequentially, on day 9 after immunization. Ten-day lymph
      nodes or 21 day spleens were tested by ELISPOT assays and flow cytometry to
      evaluate responsiveness to alpha-lactalbumin immunization in presence of
      Sunitinib and distribution of cells involved in T cell antigen priming and
      proliferation in different lymphoid compartments. In addition, therapeutic
      efficacy of the alpha-lactalbumin/ Sunitinib combination was evaluated by
      monitoring tumor growth in the 4T1 transplanted tumor model. Our studies reveal
      that concurrent administration of Sunitinib with active vaccination against a
      targeted tumor antigen inhibits priming to the immunogen due to a drastic
      decrease in CD11b+CD11c+ antigen presenting cells, leading to failure of
      vaccination. However, sequential delivery of Sunitinib timed to avoid the priming
      phase of vaccination results in the desired vaccination mediated boost in immune
      responses. 

PMID- 24105639
TI  - Enhanced magneto-optical properties of semiconductor EuS nanocrystals assisted by
      surface plasmon resonance of gold nanoparticles.
AB  - Remarkable magneto-optical properties of a new isolator material, that is,
      europium sulfide nanocrystals with gold (EuS-Au nanosystem), has been
      demonstrated for a future photo-information technology. Attachment of gold
      particles that exhibit surface plasmon resonance leads to amplification of the
      magneto-optical properties of the EuS nanocrystals. To construct the EuS-Au
      nanosystems, cubic EuS and spherical Au nanocrystals have been joined by a
      variety of organic linkers, that is, 1,2-ethanedithiol (EDT), 1,6-hexanedithiol
      (HDT), 1,10-decanedithiol (DDT), 1,4-bisethanethionaphthalene (NpEDT), or 1,4
      bisdecanethionaphthalene (NpDDT) . Formation of these systems was observed by
      XRD, TEM, and absorption spectra measurements. The magneto-optical properties of
      the EuS-Au nanosystem have been characterized by using Faraday rotation
      spectroscopy. The Faraday rotation angle of the EuS-Au nanosystem is dependent on
      the Au particle size and interparticle distance between EuS and Au nanocrystals.
      Enhancement of the Faraday rotation of EuS-Au nanosystems was observed. The spin
      configuration in the excited state of the EuS-Au nanosystem was also investigated
      using photo-assisted electron paramagnetic resonance. 

PMID- 24105640
TI  - The growing problem of stroke among young adults.
AB  - Although overall stroke incidence has been declining in developed countries,
      there is evidence that stroke in the young is increasing. Increasing incidence
      may be particularly pronounced among minorities in whom historically a higher
      burden of stroke has been reported. Compared with older adults, time spent with
      disability is longer for those affected at younger ages, and new data suggests
      that among 30-day young adult stroke survivors, increased mortality persists for
      as long as 20 years. Stroke in young adults is often missed by less experienced
      clinicians due to its unexpectedness, leading to lost opportunities for
      intervention. The causes and risk factors for stroke in the young are often rare
      or undetermined, but young adults with stroke also have a high burden of
      traditional cardiovascular risk factors, including hypertension, diabetes,
      obesity, and substance abuse. Disseminating awareness and promoting research on
      young adult stroke are steps towards reducing the burden of stroke.

PMID- 24105641
TI  - The challenge of stroke prevention with intracranial arterial stenosis.
AB  - Patients with symptomatic intracranial atherosclerotic disease have a high risk
      of recurrent stroke, and secondary prevention in these patients remains a
      challenge. Aggressive medical management of vascular risk factors is safe and
      effective for most high risk patients, but the role of endovascular and surgical
      therapies still remain uncertain. Future studies may identify novel therapeutic
      strategies for patients with intracranial atherosclerotic disease, but aggressive
      risk factor control remains the mainstay of evidenced-based treatment at this
      time. 

PMID- 24105642
TI  - Cryptogenic stroke: how to define it? How to treat it?
AB  - Stroke is a leading cause of disability worldwide. Cryptogenic strokes (CS)
      account for almost a quarter of ischemic strokes despite modern diagnostic
      evaluation. A working definition of CS based on stroke classification systems is
      essential for accurate conceptualization of this common entity. Mechanistic
      categories (potential paradoxical embolism; atherosclerotic disease of the aorta
      or supra-aortic vasculature; and occult arrhythmia) should aide in parsing the
      often heterogeneous mix of conditions included in the CS subtype. Despite efforts
      to unravel mechanisms of CS, specific or targeted recurrent stroke prevention
      strategies are lacking. For example, recent trials have shown no clear benefit of
      patent foramen ovale closure in stroke prevention after CS. There are promising
      ongoing clinical trials that will address appropriate diagnostic evaluations in
      CS as well as novel therapeutic interventions. Overall, a standardized approach
      must be framed to diagnose and manage patients with CS and guide clinical
      practice and future research. 

PMID- 24105644
TI  - Molecular doping enhances photoconductivity in polymer bulk heterojunction solar
      cells.
AB  - Addition of low concentrations (<1:100, dopant:donor) of a fluorinated p-type
      dopant, F4-TCNQ leads to a considerable enhancement of the photocurrent in
      PCDTBT:PC70 BM bulk heterojunction solar cells. As a result, the power conversion
      efficiency increases from 6.41% to 7.94 %. 

PMID- 24105643
TI  - Small vessel disease and memory loss: what the clinician needs to know to
      preserve patients' brain health.
AB  - Small vessel disease (SVD) in the brain manifests in the periventricular and deep
      white matter and radiographically is described as "leukoaraiosis". It is
      increasingly recognized as a cause of morbidity from middle age onward and this
      clinical relevance has paralleled advances in the field of neuroradiology.
      Overall, SVD is a heterogenous group of vascular disorders that may be
      asymptomatic, or a harbinger of many conditions that jeopardize brain health.
      Management and prevention focuses on blood pressure control, lifestyle
      modification, and symptomatic treatment. 

PMID- 24105647
TI  - The posterolateral mid-forearm perforator flap: anatomical study and clinical
      application.
AB  - BACKGROUND: Defects sustained at the distal forearm are common and pedicled
      perforator flaps have unique advantages in resurfacing it. The purpose of this
      study is to reappraise the anatomy of the perforator in the posterolateral aspect
      of the mid-forearm and present our clinical experience on using perforator flaps
      based on it for reconstruction of defects in the distal forearm. METHODS: This
      study was divided into anatomical study and clinical application. In the
      anatomical study, 30 preserved upper limbs were used. Clinically, 11 patients
      with defects at the forearm underwent reconstruction with the posterolateral mid
      forearm perforator flaps. The defects, ranging from 4.5 * 2.5 cm to 10.5 * 4.5
      cm, were located at the dorsal aspect of the distal forearm in 6 cases and at the
      volar aspect of the distal forearm in 5 cases. RESULTS: Three patterns of the
      perforator were observed in the posterolateral aspect of the mid-forearm, which
      originated from the posterior interosseous artery, the proximal segment of the
      radial artery or the radial recurrent artery, and the middle segment of the
      radial artery, respectively. The perforator was located 11.8 +/- 0.2 cm to 15.8
      +/- 0.4 cm inferior to the lateral humeral epicondyle. Clinically, flaps in 8
      cases survived uneventfully, while the other 3 cases suffered mild marginal
      epidermal necrosis, which was cured with continuous dress changing. CONCLUSION:
      The location of the perforator at the posterolateral aspect of the mid-forearm is
      consistent; the posterolateral mid-forearm perforator flap is particularly
      suitable to cover defects in the distal one-third of the forearm.

PMID- 24105646
TI  - Body side and predominant motor features at the onset of Parkinson's disease are
      linked to motor and nonmotor progression.
AB  - Patients with Parkinson's disease most often have asymmetric motor features at
      onset, and specific motor signs (ie, tremor versus bradykinesia and rigidity)
      frequently characterize the first few years of disease evolution. Some previous
      clinical evidence has suggested that body side and a predominance of motor
      manifestations at disease onset are linked to long-term evolution and disease
      progression. We prospectively analyzed 206 patients with Parkinson's disease
      according to the most affected side and predominant motor signs at onset.
      Patients were divided into left-side rigid-akinetic (n = 71), right-side rigid
      akinetic (n = 59), left-side tremor (n = 41), and right-side tremor (n = 35)
      subgroups. These subgroups were compared in terms of motor and cognitive
      functions, mean motor deterioration per year (calculated as the motor score
      divided by disease duration), total equivalent doses of dopaminergic drugs, and
      the presence of hallucinations and rapid eye movement sleep behavior disorder.
      Disease duration was similar in all groups. Motor fluctuations were more likely
      to occur in rigid-akinetic patients. In a multiple model analysis adjusted for
      potential confounders, faster disease progression was associated with right-side
      (P = 0.045) and rigid-akinetic onset (P = 0.001). With respect to nonmotor
      symptoms, the rigid-akinetic type was associated with increased risk of cognitive
      decline (P = 0.004) compared with the tremor type. A trend was noticed toward an
      increased risk of developing visual hallucinations in rigid-akinetic patients and
      toward an increased frequency of rapid eye movement sleep behavior disorder in
      those who had left-sided onset of symptoms. Our findings corroborate that body
      side and type of motor signs at the time of diagnosis affect the evolution of
      motor severity and may also have an impact on some nonmotor manifestations.

PMID- 24105645
TI  - The predominant protective effect of tianeptine over other antidepressants in
      models of neuronal apoptosis: the effect blocked by inhibitors of MAPK/ERK1/2 and
      PI3-K/Akt pathways.
AB  - Tianeptine (Tian) possesses neuroprotective potential, however, little is known
      about the effect of this drug in models of neuronal apoptosis. In the present
      study, we aimed (1) to compare the neuroprotective capacities of some
      antidepressants (ADs) in the models of staurosporine (St)- and doxorubicin (Dox)
      evoked cell death, activating the intracellular and the extracellular apoptotic
      pathway, respectively; (2) to identify the Tian-modulated steps underlying its
      neuroprotective action; (3) to test the effect of various ADs against Dox-evoked
      cell damage in glia cells. Primary neuronal and glia cell cultures and retinoic
      acid-differentiated human neuroblastoma SH-SY5Y (RA-SH-SY5Y) cells were co
      treated with imipramine, fluoxetine, citalopram, reboxetine, mirtazapine or Tian
      and St or Dox. The data showed the predominant neuroprotective effect of Tian
      over other tested ADs against St- and Dox-induced cell damage in primary neurons
      and in RA-SH-SY5Y cells. This effect was shown to be caspase-3-independent but
      connected with attenuation of DNA fragmentation. Moreover, neuroprotection
      elicited by Tian was blocked by pharmacological inhibitors of MAPK/ERK1/2 and PI3
      K/Akt signaling pathways as well by inhibitor of necroptosis, necrostatin-1.
      Interestingly, the protective effects of all tested ADs were demonstrated in
      primary glia cells against the Dox-evoked cell damage. The obtained data suggests
      the glial cells as a common target for protective action of various ADs whereas
      in relation to neuronal cells only Tian possesses such properties, at least
      against St- and Dox-induced cell damage. Moreover, this neuroprotective effect of
      Tian is caspase-3-independent and engages the regulation of survival pathways
      (MAPK/ERK1/2 and PI3-K/Akt). 

PMID- 24105648
TI  - Local spin analysis and chemical bonding.
AB  - The electronic structure of main-group diatomic molecules is discussed in the
      light of local spin analysis. A deep investigation into the origin of local spins
      and their coupling is presented. It is shown that the presence of significant
      local spins in bonded molecules flags deviations from the classical bonding
      prototypes. For the notorious example of the C2 molecule, the local spin analysis
      indicates that its ground state has all ingredients to be categorized as a
      diradical. 

PMID- 24105649
TI  - Microtransplantation of whole ganglionic eminence cells ameliorates motor
      deficit, enlarges the volume of grafts, and prolongs survival in a rat model of
      Huntington's disease.
AB  - Studies have demonstrated that embryonic cell therapy is a potential approach for
      the treatment of Huntington's disease (HD). However, because of the limited
      resource of embryos, greater attention is needed in developing more efficient
      surgical techniques that not only enhance the therapy outcome but also avoid
      inefficient therapeutics of transplantation. In this study, we explored the
      curative effects of two different transplantation methods using a rat model of
      HD. Whole ganglionic eminence (WGE) cells or phosphate-buffered saline were
      transplanted into unilateral striatum of quinolinic acid (QA)-lesioned rats using
      microtransplantation instruments (with an outer diameter of 50 MUm) or
      traditional transplantation instruments (with an outer diameter of 470 MUm).
      Apomorphine-induced rotation test and adjusting step test were assessed after QA
      induced lesion and 2, 4, 6, 8, 10, and 12 weeks after transplantation. The
      expression of neuronal nuclei (NeuN), dopamine, cAMP-regulated phosphoprotein of
      molecular weight 32 kDa (DARPP-32), and glial fibrillary acidic protein (GFAP)
      was analyzed at 12 weeks after transplantation. We observed that
      microtransplanted rats performed better in the stepping test and had higher
      numbers of DARPP-32-positive cells compared with traditionally transplanted rats.
      Moreover, microtransplantation group showed lower GFAP expression surrounding the
      grafts in unilateral striatum and a higher survival rate posttransplantation
      compared with the traditional transplantation group. We conclude that
      microtransplantation is capable of enhancing therapeutic efficacy in the rat
      model of HD. This finding establishes the basis of an alternative transplantation
      strategy for treatment of HD.

PMID- 24105651
TI  - c-Jun NH2 -terminal kinase is a critical node in the death of CD4+ CD8+
      thymocytes during Salmonella enterica serovar Typhimurium infection.
AB  - Thymic atrophy, due to the depletion of CD4(+) CD8(+) thymocytes, is observed
      during infections with numerous pathogens. Several mechanisms, such as
      glucocorticoids and inflammatory cytokines, are known to be involved in this
      process; however, the roles of intracellular signaling molecules have not been
      investigated. In this study, the functional role of c-Jun NH2 -terminal kinase
      (JNK) during infection-induced thymic atrophy was addressed. The levels of
      phosphorylated JNK in immature CD4(+) CD8(+) thymocytes from C57BL/6 (Nramp
      deficient) and 129/SvJ (Nramp-sufficient) mice were increased upon oral infection
      of mice with Salmonella enterica serovar Typhimurium (S. typhimurium).
      Furthermore, inhibition of JNK signaling, but not ERK or p38 MAPK, prevented the
      in vitro death of infected thymocytes. Importantly, the in vivo inhibition of JNK
      signaling with SP600125 protected C57BL/6 CD4(+) CD8(+) thymocytes from depletion
      via multiple mechanisms as follows: lower intracellular ROS, inflammatory
      cytokines, Bax and caspase 3 activity, increase in Bcl-xL amounts, and prevention
      of the loss in mitochondrial membrane potential. Notably, thymic architecture was
      preserved in infected mice treated with SP600125. Overall, this study identifies
      a novel role for JNK as a crucial regulator of the death of CD4(+) CD8(+)
      thymocytes during S. typhimurium infection. 

PMID- 24105652
TI  - Cariogenic potential of milk and infant formulas: a systematic review.
AB  - AIM: To assess the cariogenic potential of cow's milk, human milk and infant
      formulas in comparison to sucrose in animal models. METHODS: Electronic search of
      the following databases were undertaken: PubMed-MEDLINE, MeSH and ingentaconnect.
      In addition, the reference lists of all eligible studies were searched.
      Characteristics such as animal species were used; comparisons and outcomes
      measured were analysed. RESULTS: The search yielded a total of 13 articles of
      which six studies met the inclusion criteria and seven were excluded. All the six
      included studies used rat models for assessing the cariogenic potential of the
      test groups. Cow's milk was compared with sucrose in all of the six studies,
      reporting cow's milk to be less cariogenic than sucrose. Two studies compared
      human milk to sucrose and reported human milk to be less cariogenic than sucrose,
      but more than that of cow's milk. Although infant formulas were compared with
      sucrose in four studies, their cariogenic potential was a matter of some
      ambiguity. CONCLUSION: The evidence suggests that cow's milk and human milk are
      less cariogenic than sucrose, with cow's milk being the least cariogenic. The
      cariogenic potential of infant formulas varied across the studies, with some
      being as cariogenic as sucrose.

PMID- 24105653
TI  - Defective control of vitamin D receptor-mediated epithelial STAT1 signalling
      predisposes to severe respiratory syncytial virus bronchiolitis.
AB  - Respiratory syncytial virus (RSV) infection causes bronchiolitis in infants with
      seasonal frequency, for which vitamin D deficiency and a well-described
      polymorphism in the vitamin D receptor (VDR) FokI are important risk factors.
      Recent studies suggest that vitamin D regulates immune pathways in airway
      epithelial cells during RSV infection. It is not understood why the VDR FokI
      polymorphism predisposes to severe RSV bronchiolitis. We investigated how the VDR
      FokI polymorphism regulates the epithelial response to RSV infection. To this
      end, we over-expressed the normal and FokI VDR variants in A549 airway epithelial
      cells. Vitamin D restrained the expression of both NFkappaB- and STAT1-induced
      antiviral genes. However, while NFkappaB control by vitamin D remained intact,
      both RSV-induced phosphorylation of STAT1 and expression of its downstream
      targets, IRF1 and IRF7, escaped vitamin D control in FokI epithelial cells. The
      poor capacity of vitamin D to regulate IRF1 in FokI VDR-expressing cells was
      recapitulated using blood samples from normal and FokI VDR-genotyped healthy
      donors. Hence, we provide mechanistic insight that the FokI VDR polymorphism
      renders STAT1-mediated antiviral immune reactions to RSV infection non-responsive
      to vitamin D control, resulting in enhanced immunopathology and exacerbated RSV
      bronchiolitis.

PMID- 24105654
TI  - The role of epidemiology in the era of molecular epidemiology and genomics:
      Summary of the 2013 AJE-sponsored Society of Epidemiologic Research Symposium.
AB  - On June 20, 2013, the American Journal of Epidemiology sponsored a symposium at
      the Society for Epidemiologic Research's 46th Annual Meeting in Boston,
      Massachusetts, entitled, "What Is the Role of Epidemiology in the Era of
      Molecular Biology and Genomics?" The future of epidemiology depends on innovation
      in generating interesting and important testable hypotheses that are relevant to
      population health. These new strategies will depend on new technology, both in
      measurement of agents and environment and in the fields of pathophysiology and
      outcomes, such as cellular epidemiology and molecular pathology. The populations
      to be studied, sample sizes, and study designs should be selected based on the
      hypotheses to be tested and include case-control, cohort, and clinical trials.
      Developing large mega cohorts without attention to specific hypotheses is
      inefficient, will fail to address many associations with high-quality data, and
      may well produce spurious results.

PMID- 24105655
TI  - Therapy-induced enrichment of putative lung cancer stem-like cells.
AB  - Tumour drug resistance is a major issue in the management of lung cancer patients
      as almost all lung tumours are either intrinsically resistant or quickly develop
      acquired resistance to chemotherapeutic drugs. Cancer drug resistance has
      recently been linked, at least in part, to the existence of cancer stem-like
      cells (CSLCs), a small sub-population of cells within the tumour that possess
      stem-like properties. CSLCs are often isolated by fluorescence activated cell
      sorting (FACS) according to the expression of certain stem-like cell membrane
      markers. Conflicting results regarding the specificity of particular stem cell
      surface markers for isolating CSLCs have, however, been recently reported.
      Therefore, alternative strategies enabling the identification and study of CSLCs
      should be considered, particularly in tumour types where appropriate stem cell
      markers are not well established and validated, like in lung cancer. In this
      article, we review data indicating therapy-selection as a valid approach for
      putative lung CSLCs enrichment. We believe that this strategy would be
      determinant for correctly assessing and characterising the sub-populations of
      CSLCs that are able to survive chemo or radiotherapy regimens and, at the same
      time, also have the ability to recapitulate and sustain tumour growth. Using
      therapy-induced enrichment of CSLCs may, therefore, prove to be an extremely
      useful method for studying CSLCs and provide new clues regarding potential
      therapeutic targets for their efficient elimination, which will undoubtedly play
      a decisive role in improving lung cancer patients' survival. 

PMID- 24105656
TI  - What are the best management strategies for radiation-induced xerostomia?

PMID- 24105657
TI  - Synthesis of an orthogonal topological analogue of helicene.
AB  - The synthesis of an orthogonal topological pentamer analogue of helicene is
      presented. This analogue forms a tubular structure with its aromatic systems
      directed parallel to the axis of propagation, which creates a cavity with the
      potential to function as a host molecule. The synthetic strategy reported, based
      on a series of repeating Friedlander condensations that utilize pyrido[3,2
      d]pyrimidine moieties as protected amino aldehydes, allows for the facile access
      of higher generations of helical, tubular structures. As a result of the
      synthetic strategy, only a helical isomer of the pentamer is possible. The
      structure and absolute configuration of the pentamer were elucidated from a
      combination of NMR spectroscopic data, optical properties, X-ray structures, and
      by comparison of an experimental electronic circular dichroism spectrum to a
      calculated spectrum. 

PMID- 24105658
TI  - Apathy is an independent risk factor for incident cardiovascular disease in the
      older individual: a population-based cohort study.
AB  - OBJECTIVE: Although depression is considered to be associated with cardiovascular
      disease (CVD), specifically symptoms of apathy have been strongly associated with
      a history of CVD in recent studies. In this study, we prospectively assess
      whether symptoms of apathy and depression are independent risk factors for
      incident CVD and stroke. METHODS: We carried out a prospective cohort study of
      1810 community-dwelling older individuals (70-78 years) without a history of CVD
      or stroke. Symptoms of apathy and depression were assessed with the 15-item
      Geriatric Depression Scale. Incident CVD and stroke were assessed after 2 years
      follow-up. The associations of symptoms of apathy and depression with incident
      CVD and stroke were analyzed separately using logistic regression analysis.
      RESULTS: Symptoms of apathy and depression were present in 281 (15.5%) and 266
      (14.7%) participants, respectively. Incident CVD occurred in 62 (3.5%)
      participants and stroke in 55 (3.1%) participants. Apathy was associated with
      incident CVD after adjustment for demographics and cardiovascular risk factors
      (odds ratio (OR) = 2.60, 95% CI = 1.46-4.65). Exclusion of subjects with
      depressive symptoms yielded a similar OR (2.94, 95% CI = 1.45-5.96, n = 1544). No
      association was found between depressive symptoms and incident CVD. Neither
      apathy symptoms nor depressive symptoms were associated with incident stroke.
      CONCLUSIONS: Apathy, but not depression, is a strong, independent risk factor for
      incident CVD. It may be a marker of underlying vascular disease. By its nature,
      apathy may cause non-adherence to a healthy lifestyle, diminished activities, and
      possibly even withdrawal from clinical care aimed at improving vascular risk
      profiles.

PMID- 24105660
TI  - Conjugated polymeric zwitterions as efficient interlayers in organic solar cells.
AB  - Conjugated polymeric zwitterions, when utilized as interlayer materials in bulk
      heterojunction organic solar cells, lead to significantly enhanced power
      conversion efficiencies. The electrostatic model of self-aligning dipolar side
      groups in the vicinity of the metal surface rationalizes the effects of reduced
      cathode work function, a key factor behind the observed enhanced efficiency. 

PMID- 24105659
TI  - Effects of the comminution rate and microbial contamination of particles in the
      rumen on in situ estimates of protein and amino acid digestion of expeller palm
      kernel and rapeseed meal.
AB  - BACKGROUND: Microbial corrected effective in situ estimates of ruminal undegraded
      fraction (RU) and intestinal effective digestibility (IED) of dry matter (DM),
      crude protein (CP) and amino acids (AA) of expeller palm kernel (EPK) and
      rapeseed meal (RSM) were measured on three rumen- and duodenum-cannulated wethers
      using 15N labelling techniques and considering ruminal rates of comminution
      (k(c)) and outflow (k(p)) of particles. RESULTS: The lack of k(c) and microbial
      correction overestimated the RU of DM by 4.91% (EPK) and 9.88% (RSM). The lack of
      this correction also overestimated in both feeds the RU of CP, individual and
      total (TAA) AA as well as the IED of DM, CP, TAA and most AA. RU estimates were
      higher for CP than for TAA, but the opposite was observed for IED. The intestinal
      digested fraction was higher for CP than for TAA: 17.4% (EPK) and 13.8% (RSM).
      Digestion led to large changes in the essential AA profile in both feeds.
      CONCLUSION: The lack of k(c) and microbial correction as well as CP-based results
      leads to considerable overestimations in the protein use of both feeds. Digestion
      aggravates the lysine deficiency of EPK but has global positive effects in the
      absorbed profile of RSM.

PMID- 24105661
TI  - 4-Nitro-3-(5-tetrazole)furoxan and its salts: synthesis, characterization, and
      energetic properties.
AB  - A series of new energetic salts based on 4-nitro-3-(5-tetrazole)furoxan (HTNF)
      has been synthesized. All of the salts have been fully characterized by nuclear
      magnetic resonance ((1)H and (13)C), infrared (IR) spectroscopy, elemental
      analysis, and differential scanning calorimetry (DSC). The crystal structures of
      neutral HTNF (3) and its ammonium (4) and N-carbamoylguanidinium salts (9) have
      been determined by single-crystal X-ray diffraction analysis. The densities of 3
      and its nine salts were found to range from 1.63 to 1.84 g cm(-3). Impact
      sensitivities have been determined by hammer tests, and the results ranged from 2
      J (very sensitive) to >40 J (insensitive). Theoretical performance calculations
      (Gaussian 03 and EXPLO 5.05) provided detonation pressures and velocities for the
      ionic compounds 4-12 in the ranges 25.5-36.2 GPa and 7934-8919 m s(-1),
      respectively, which make them competitive energetic materials.

PMID- 24105664
TI  - Relapses in the treatment of genotype 2 viral hepatitis C, a cause of concern in
      the blacks.

PMID- 24105663
TI  - Neural and physiological responses to a cold pressor challenge in healthy
      adolescents.
AB  - Abnormal autonomic function is common in pediatric diseases. Assessment of
      central mechanisms underlying autonomic challenges may reveal vulnerabilities
      antecedent to system failure. Our objective was to characterize central markers
      and physiological responses to a cold pressor challenge in normal children as a
      critical step for establishing such screening. We performed functional magnetic
      resonance imaging (fMRI) and collected physiological measures during cold
      application to the foot in 24 healthy adolescents (15.5 +/- 0.4 years, 13 male).
      The protocol included a 120-sec baseline, 120-sec right-foot cold water immersion
      (4 degrees C), and 120-sec recovery. Analyses included heart rate (HR) cross
      correlations with fMRI signals. Cold application increased HR 13% 5-7 sec after
      onset, which remained elevated throughout the challenge. Respiratory rate
      transiently increased (peak 22%), then declined (nadir 12% below baseline),
      before normalizing at 75 sec. Cold onset rapidly increased somatosensory cortex
      and medullary signals, which fell after 25 sec. Right anterior insular cortex
      signals increased early, followed after 20 sec by the left anterior insula, with
      HR declining 8 sec later. Amygdalae signals also rose, but signals declined in
      the posterior cingulate cortex, caudate nucleus, hippocampus, and hypothalamus.
      Declining signals appeared late in the cerebellar fastigial nuclei (60-120 sec),
      and in the pons and thalamus. Somatosensory cortex, fastigial nuclei, and
      hypothalamic responses were principally left-sided, with bilateral responses
      elsewhere. Late left anterior insula responses likely underlie the HR decline;
      the late cerebellar pattern may modulate recovery. The laterality, timing, and
      amplitude of normative responses and rostral response differentiation indicate
      the complex integration of adolescent autonomic processing and provide indices
      for pathological comparisons.

PMID- 24105662
TI  - Common community-acquired infections and subsequent risk of multiple myeloma: a
      population-based study.
AB  - The role of bacteria and viruses as aetiological agents in the pathogenesis of
      cancer has been well established for several sites, including a number of
      haematological malignancies. Less clear is the impact of such exposures on the
      subsequent development of multiple myeloma (MM). Using the population-based U.S.
      Surveillance Epidemiology and End Results-Medicare dataset, 15,318 elderly MM and
      200,000 controls were identified to investigate the impact of 14 common community
      acquired infections and risk of MM. Odds ratios (ORs) and associated 95%
      confidence intervals (CIs) were adjusted for sex, age and calendar year of
      selection. The 13-month period prior to diagnosis/selection was excluded. Risk of
      MM was increased by 5-39% following Medicare claims for eight of the investigated
      infections. Positive associations were observed for several infections including
      bronchitis (adjusted OR 1.14, 95% CI 1.09-1.18), sinusitis (OR 1.15, 95% CI 1.10
      1.20) pneumonia (OR 1.27, 95% CI 1.21-1.33), herpes zoster (OR 1.39, 95% CI 1.29
      1.49) and cystitis (OR 1.09, 95% CI 1.05-1.14). Each of these infections remained
      significantly elevated following the exclusion of more than 6 years of claims
      data. Exposure to infectious antigens may therefore play a role in the
      development of MM. Alternatively, the observed associations may be a
      manifestation of an underlying immune disturbance present several years prior to
      MM diagnosis and thereby part of the natural history of disease progression. 

PMID- 24105665
TI  - Liver necrosis following corrosive ingestion.
AB  - We describe a rare sequel of corrosive ingestion. In this patient, ingestion of a
      corrosive led to ischemic necrosis of the entire left lobe of the liver (segments
      II, III, and IV) in addition to causing full-thickness necrosis of the
      esophagus/stomach, infarction of the spleen, and injury to the left
      hemidiaphragm. Solid organ involvement following corrosive ingestion is uncommon.
      Although involvement of the spleen and pancreas from extension of corrosive burns
      from the adjacent stomach is occasionally described, involvement of the liver
      following corrosive ingestion has not been reported in the literature till date. 

PMID- 24105666
TI  - Absence of G1528C mutation in long-chain 3-hydroxyacyl-CoA dehydrogenase in four
      Indian patients with pregnancy-related liver disease.

PMID- 24105667
TI  - High resolution esophageal manometry--the switch from "intuitive" visual
      interpretation to Chicago classification.
AB  - High resolution esophageal manometry (HREM) has been interpreted all along by
      visual interpretation of color plots until the recent introduction of Chicago
      classification which categorises HREM using objective measurements. It compares
      HREM diagnosis of esophageal motor disorders by visual interpretation and Chicago
      classification. Using software Trace 1.2v, 77 consecutive tracings diagnosed by
      visual interpretation were re-analyzed by Chicago classification and findings
      compared for concordance between the two systems of interpretation. STATISTICAL
      ANALYSIS: Kappa agreement rate between the two observations was determined. There
      were 57 males (74 %) and cohort median age was 41 years (range: 14-83 years).
      Majority of the referrals were for gastroesophageal reflux disease, dysphagia and
      achalasia. By "intuitive" visual interpretation, the tracing were reported as
      normal in 45 (58.4 %), achalasia 14 (18.2 %), ineffective esophageal motility 3
      (3.9 %), nutcracker esophagus 11 (14.3 %) and nonspecific motility changes 4 (5.2
      %). By Chicago classification, there was 100 % agreement (Kappa 1) for achalasia
      (type 1: 9; type 2: 5) and ineffective esophageal motility ("failed peristalsis"
      on visual interpretation). Normal esophageal motility, nutcracker esophagus and
      nonspecific motility disorder on visual interpretation were reclassified as rapid
      contraction and esophagogastric junction (EGJ) outflow obstruction by Chicago
      classification. Chicago classification identified distinct clinical phenotypes
      including EGJ outflow obstruction not identified by visual interpretation. A
      significant number of unclassified HREM by visual interpretation were also
      classified by it.

PMID- 24105668
TI  - Are food restriction and pressure-to-eat parenting practices associated with
      adolescent disordered eating behaviors?
AB  - OBJECTIVE: To examine associations between parental pressure-to-eat and food
      restriction and adolescent disordered eating behaviors, within a sample of parent
      adolescent pairs. METHOD: Adolescents (N = 2,231) and their parents (N = 3,431)
      participated in two, coordinated, population-based studies designed to examine
      factors associated with weight and weight-related behaviors in adolescents.
      RESULTS: Overall, higher levels of pressure-to-eat or food restriction were
      significantly and positively associated with use of disordered eating behaviors
      among boys. For every one unit increase [Scale Range: 1 (low control) to 4 (high
      control)] in mothers' food restriction, boys were twice as likely to engage in
      extreme weight control behaviors (p <= .01). Examination of the association
      between food-related parenting practices and disordered eating behaviors among
      girls revealed fewer significant associations. However, analyses revealed that
      for every one unit increase in mothers' food restriction, girls were 1.33 times
      more likely to engage in extreme weight control behaviors (p = .04). DISCUSSION:
      Study findings provide evidence of an association between controlling food
      related parenting practices and adolescent disordered eating behaviors,
      particularly in boys. Future longitudinal research is needed to establish
      directionality of observed associations.

PMID- 24105669
TI  - Foot reconstruction using a serratus anterior muscle flap from the same donor
      site after failure of a thoracodorsal artery perforator flap.
AB  - The free flap failure rate for the lower extremities is high, which adversely
      affects limb salvage efforts. In this article, we report a case of failure of a
      thoracodorsal artery perforator flap, which was simultaneously reconstructed with
      a serratus anterior muscle flap from the same donor site. A 56-year-old male
      patient had infected wound for 3 months due to Achilles tendon rupture. We
      reconstructed the defect using a thoracodorsal artery perforator flap. However, 2
      days after the operation, we found the congested flap. We were obliged to discard
      the whole flap and harvested a serratus anterior muscle flap from the same donor
      site. The patient's foot healed uneventfully. After flap failure, the use of a
      second free flap from the same donor site may be an effective and safe procedure
      in specific cases.

PMID- 24105670
TI  - Developing biomarkers to predict benefit from HGF/MET pathway inhibitors.
AB  - Activation of the MET signalling pathway is critical in regulating multiple
      cellular processes underlying tumourigenic growth and has represented an
      attractive target for therapeutic intervention in cancer. Early stage clinical
      studies of multiple agents targeting this pathway have been undertaken,
      frequently in unselected patient cohorts with variable results. Promising data in
      patient subgroups in these studies indicate the need for predictive biomarkers to
      identify the patients most likely to benefit from these therapies. In this
      review, we discuss the current knowledge of mechanisms of MET activation, the
      status of the clinical evaluation of MET-targeted therapies, the associated
      efforts to identify and validate biomarkers, and the considerations and
      challenges for potential development of companion diagnostics.

PMID- 24105671
TI  - What are the criteria for terminating treatment for necrotizing (malignant)
      otitis externa?

PMID- 24105672
TI  - Acute cognitive impairment in patients with multiple myeloma undergoing
      autologous hematopoietic stem cell transplant.
AB  - BACKGROUND: Few studies have examined the acute effects of autologous
      hematopoietic stem cell transplantation (Au-HSCT) on the neuropsychological
      functioning of patients with multiple myeloma (MM). The prevalence of cognitive
      deficits after induction chemotherapy (pre-AuHSCT) was examined in patients with
      MM, clinically significant changes in cognitive function 1 and 3 months post
      AuHSCT were determined, and patients who may be vulnerable to cognitive decline
      during this period were identified. METHODS: A total of 53 patients with MM were
      recruited pre-AuHSCT. Neuropsychological tests measuring multiple cognitive
      domains (attention, psychomotor speed, learning/memory, language, executive
      function, motor function) were administered pre-AuHSCT and 1 and 3 months post
      AuHSCT. A pretreatment assessment was not available. An Overall Cognitive
      Function Index was computed to determine cognitive impairment pre-AuHSCT, and a
      practice-effect-adjusted Reliable Change Index was used to determine cognitive
      change over time. RESULTS: Overall, deficits were more frequent in
      learning/memory, executive function, motor function, and psychomotor speed.
      Before AuHSCT, 47% of patients (25/53) exhibited cognitive impairment as
      determined by the Overall Cognitive Function Index. One month post-AuHSCT, 49% of
      patients (20/41) demonstrated clinically significant decline on 1 or more
      measures; 3 months post-AuHSCT, 48% (14 of 29 patients) showed decline on 1 or
      more measures. Older patients, minorities, and those with advanced disease, more
      induction cycles, or postinduction deficits showed greater vulnerability to
      decline. CONCLUSIONS: Nearly half of the patients showed vulnerability to
      impairment in learning/memory or executive function after receiving induction
      therapy, and the prevalence of impairment remained high post-AuHSCT. Awareness of
      cognitive impairment and associated risk factors in actively treated patients is
      important for considering psychosocial or other support for patients with acute
      cognitive symptoms.

PMID- 24105673
TI  - Antioxidant changes during domestic food processing of the white shaft and green
      leaves of leek (Allium ampeloprasum var. porrum).
AB  - BACKGROUND: Evaluating the effect of domestic cooking on the health benefits of
      vegetables has great practical importance. However, only a limited number of
      reports provide information on the effect of these treatments on the antioxidant
      capacity, polyphenol and S-alk(en)yl-L-cysteine sulfoxide (ACSO, e.g. isoalliin
      and methiin) content of the white shaft and green leaves of leek (Allium
      ampeloprasum var. porrum). RESULTS: In the present study, the antioxidant
      capacity of leek was highly influenced by cooking (blanching, boiling and
      steaming). Boiling had a negative effect on total phenolic content in the white
      shaft and green leaves. An obvious increase could be observed in the antioxidant
      capacity of the steamed green leaves, while steaming did not influence the
      polyphenolic content. Remarkably, blanching resulted in a slight increase in the
      ACSO content. Subjecting leek samples to a longer thermal treatment appeared to
      have a negative influence on the ACSO content in leek. Steaming was also
      responsible for a decrease in ACSOs. Methiin was less susceptible to heat
      treatment than isoalliin. CONCLUSION: In general, steaming appeared to be
      responsible for better retention of the bioactive compounds present in leek
      compared with boiling.

PMID- 24105674
TI  - Neuromodulatory nerve regeneration: adipose tissue-derived stem cells and
      neurotrophic mediation in peripheral nerve regeneration.
AB  - Peripheral nerve injury requiring nerve gap reconstruction remains a major
      problem. In the quest to find an alternative to autogenous nerve graft
      procedures, attempts have been made to differentiate mesenchymal stem cells into
      neuronal lineages in vitro and utilize these cellular constructs for nerve
      regeneration. Unfortunately, this has produced mixed results, with no definitive
      procedure matching or surpassing traditional nerve grafting procedures. This
      review presents a different approach to nerve regeneration. The literature was
      reviewed to evaluate current methods of using adipose-derived stem cells (ADSCs)
      for peripheral nerve regeneration in in vivo models of animal peripheral nerve
      injury. The authors present cited evidence for directing nerve regeneration
      through paracrine effects of ADSCs rather than through in vitro nerve
      regeneration. The paracrine effects rely mainly, but not solely, on the
      elaboration of nerve growth factors and neurotrophic mediators that influence
      surrounding host cells to orchestrate in vivo nerve regeneration. Although this
      paradigm has been indirectly referred to in a host of publications, few major
      efforts for this type of neuromodulatory nerve regeneration have been
      forthcoming. The ADSCs are initially "primed" in vitro using specialized
      controlled medium (not for neuronal differentiation but for sustainability) and
      then incorporated into a hydrogel base matrix designed for this purpose. This
      core matrix is then introduced into a natural collagen-based nerve conduit. The
      prototype design concepts, evidence for paracrine influences, and regulatory
      hurdles that are avoided using this approach are discussed.

PMID- 24105675
TI  - Redox- and temperature-controlled drug release from hollow mesoporous silica
      nanoparticles.
AB  - A controlled drug-delivery system has been developed based on mesoporous silica
      nanoparticles that deliver anticancer drugs into cancer cells with minimized side
      effects. The copolymer of two oligo(ethylene glycol) macromonomers cross-linked
      by the disulfide linker N,N'-bis(acryloyl)cystamine is used to cap hollow
      mesoporous silica nanoparticles (HMSNs) to form a core/shell structure. The HMSN
      core is applied as a drug storage unit for its high drug loading capability,
      whereas the polymer shell is employed as a switch owing to its redox/temperature
      dual responses. The release behavior in vitro of doxorubicin demonstrated that
      the loaded drugs could be released rapidly at higher temperature or in the
      presence of glutathione (GSH). Thus, the dual-stimulus polymer shell exhibiting a
      volume phase transition temperature higher than 37  degrees C can effectively
      avoid drug leakage in the bloodstream owing to the swollen state of the shell.
      Once internalized into cells, the carriers shed the polymer shell because of
      cleavage of the disulfide bonds by GSH, which results in the release of the
      loaded drugs in cytosol. This work may prove to be a significant development in
      on-demand drug release systems for cancer therapy.

PMID- 24105676
TI  - Efficacy of lamivudine combined with adefovir dipivoxil versus entecavir
      monotherapy in patients with hepatitis B-associated decompensated cirrhosis: A
      meta-analysis.
AB  - Whether the combination of lamivudine (LAM) plus adefovir (ADV) de novo is more
      effective than entecavir (ETV) monotherapy in patients with HBV-associated
      decompensated cirrhosis is still controversial. We searched seven randomized
      controlled trials that included 411 patients in this meta-analysis. There are 205
      and 206 patients in these two groups separately. The pooled risk ratio (RR) and
      mean difference (MD) were used to assess the treatment effects. ETV monotherapy
      significantly improved Child-Turcotte-Pugh (CTP) scores (MD = 0.33, 95%CI [0.21
      0.44], P < .00001), and was associated with lower rates of serum creatinine
      increase compared LAM + ADV combination therapy (RR = 4.76, 95%CI [1.11-20.33], P
      = .04) at 48 weeks. The reduction of alanine aminotransferase (ALT) levels, HBV
      DNA levels, the rate of ALT normalization, undetectable HBV DNA, HBV e antigen
      (HBeAg) loss, HBeAg seroconversion and mortality were similar between the two
      groups. ETV is more effective than LAM + ADV in improving CTP scores at 48 weeks.
      Both of the LAM + ADV and ETV had similar efficacy in improving virological and
      biochemical parameters at 48 weeks of follow-up. Furthermore, use of these agents
      in decompensated HBV patients was generally safe and well tolerated at 48 weeks.
      However, the nephrotoxicity of ADV, and the potential adverse effects of ETV
      should be considered and monitored during prolonged therapy.

PMID- 24105677
TI  - 25th anniversary article: key points for high-mobility organic field-effect
      transistors.
AB  - Remarkable progress has been made in developing high performance organic field
      effect transistors (OFETs) and the mobility of OFETs has been approaching the
      values of polycrystalline silicon, meeting the requirements of various electronic
      applications from electronic papers to integrated circuits. In this review, the
      key points for development of high mobility OFETs are highlighted from aspects of
      molecular engineering, process engineering and interface engineering. The
      importance of other factors, such as impurities and testing conditions is also
      addressed. Finally, the current challenges in this field for practical
      applications of OFETs are further discussed. 

PMID- 24105678
TI  - A preliminary examination of a nonpurging compensatory eating disorder.
AB  - OBJECTIVE: To evaluate correlates of a compensatory eating disorder (CED)
      characterized by recurrent nonpurging compensatory behaviors in the absence of
      objectively large binge episodes among normal weight individuals who endorse
      undue influence of weight/shape on self-evaluation as possible indicators of
      clinical significance and distinctiveness. METHOD: Women with CED (n = 20), women
      with bulimia nervosa (BN) (n = 20), and controls (n = 20) completed an interview
      and questionnaires assessing eating disorder and general psychopathology and
      weight history. RESULTS: Compared with controls, women with CED reported
      significantly greater body image disturbance and disordered eating, higher
      anxiety proneness, increased perfectionism, and greater weight suppression.
      Compared with BN, CED was associated with significantly less body image
      disturbance, disordered eating, weight suppression, and lower likelihood of being
      overweight in childhood. However, CED and BN did not differ on anxiety proneness
      or perfectionism. DISCUSSION: CED merits further examination to determine whether
      it is a clinically significant and distinct eating disorder.

PMID- 24105679
TI  - Usefulness of the SPACE pulse sequence at 1.5T MR cholangiography: comparison of
      image quality and image acquisition time with conventional 3D-TSE sequence.
AB  - PURPOSE: To prospectively evaluate the image quality and image acquisition time
      at 3D magnetic resonance cholangiopancreatography (MRCP) using sampling
      perfection with application optimized contrasts (SPACE) and conventional turbo
      spin-echo (TSE) sequences. MATERIALS AND METHODS: We acquired navigator-triggered
      SPACE and conventional 3D-TSE MRCP images using the same parameters where
      possible for 30 patients and compared the image acquisition time, contrast, and
      contrast-to-noise ratio (CNR) of the common bile duct (CBD). Two radiologists
      performed qualitative analyses using a 4-point scale. RESULTS: Image acquisition
      time was 31% shorter with the SPACE than the conventional TSE sequence (248.9 +/-
      73.0 sec vs. 360.5 +/- 99.9 sec, P < 0.01). The contrast and CNR was
      significantly higher with the SPACE technique than conventional TSE (39.4 +/-
      14.7 vs. 33.5 +/- 14.2, P < 0.01 and 18.6 +/- 7.8 vs. 15.5 +/- 9.3, P = 0.03).
      All visual scores were higher for the SPACE than the conventional TSE sequence;
      there was a significant difference in motion artifacts and the depiction of the
      CBD and the left hepatic and main pancreatic duct (P < 0.05). CONCLUSION: On the
      1.5T MR scanner, 3D-MRCP with the SPACE sequence significantly improved the
      contrast and CNR of CBD. In addition, it yielded images of better quality at 30%
      shorter acquisition time than constant refocusing pulse flip angle TSE.

PMID- 24105681
TI  - Opened end-to-side technique for end-to-side anastomosis and analyses by an
      elastic true-to-scale silicone rubber model.
AB  - The end-to-side anastomosis is frequently used in microvascular free flap
      transfer, but detailed rheological analyses are not available. The purpose of
      this study was to introduce a new modified end-to-side (Opened End-to-Side, OES-)
      technique and compare the resulting flow pattern to a conventional technique. The
      new technique was based on a bi-triangulated preparation of the branching-vessel
      end, resulting in a "fish-mouthed" opening. We performed two different types of
      end-to-side anastomoses in forty pig coronary arteries and produced one elastic,
      true-to-scale silicone rubber model of each anastomosis. Then we installed the
      transparent models in a circulatory experimental setup that simulated the
      physiological human blood flow. Flow velocity was measured with the one-component
      Laser-Doppler-Anemometer system, recording flow axial and perpendicular to the
      model at four defined cross-sections for seven heart cycles in each model.
      Maximal and minimal axial velocities ranged in the conventional model between
      0.269 and -0.122 m/s and in the experimental model between 0.313 and -0.153 m/s.
      A less disturbed flow velocity distribution was seen in the experimental model
      distal to the anastomosis. The OES-technique showed superior flow profiles distal
      to the anastomosis with minor tendencies of flow separation and represents a new
      alternative for end-to-side anastomosis.

PMID- 24105680
TI  - Interleukin-33/ST2 axis promotes breast cancer growth and metastases by
      facilitating intratumoral accumulation of immunosuppressive and innate lymphoid
      cells.
AB  - The role of IL-33/ST2 pathway in antitumor immunity is unclear. Using 4T1 breast
      cancer model we demonstrate time-dependent increase of endogenous IL-33 at both
      the mRNA and protein levels in primary tumors and metastatic lungs during cancer
      progression. Administration of IL-33 accelerated tumor growth and development of
      lung and liver metastases, which was associated with increased intratumoral
      accumulation of CD11b(+) Gr-1(+) TGF-beta1(+) myeloid-derived suppressor cells
      (MDSCs) that expressed IL-13alpha1R, IL-13-producing Lin(-) Sca-1(+) ST2(+)
      innate lymphoid cells (ILCs) and CD4(+) Foxp3(+) ST2(+) IL-10(+) Tregs compared
      to untreated mice. Higher incidence of monocytic vs. granulocytic MDSCs and
      plasmocytoid vs. conventional dendritic cells (DCs) was present in mammary tumors
      of IL-33-treated mice. Intratumoral NKp46(+) NKG2D(+) and NKp46(+) FasL(+) cells
      were markedly reduced after IL-33 treatment, while phosphate-buffered saline
      treated ST2-deficient mice had increased frequencies of these tumoricidal natural
      killer (NK) cells compared to untreated wild-type mice. IL-33 promoted
      intratumoral cell proliferation and neovascularization, which was attenuated in
      the absence of ST2. Tumor-bearing mice given IL-33 had increased percentages of
      splenic MDSCs, Lin(-) Sca-1(+) ILCs, IL-10-expressing CD11c(+) DCs and
      alternatively activated M2 macrophages and higher circulating levels of IL-10 and
      IL-13. A significantly reduced NK cell, but not CD8(+) T-cell cytotoxicity in IL
      33-treated mice was observed and the mammary tumor progression was not affected
      when CD8(+) T cells were in vivo depleted. We show a previously unrecognized role
      for IL-33 in promoting breast cancer progression through increased intratumoral
      accumulation of immunosuppressive cells and by diminishing innate antitumor
      immunity. Therefore, IL-33 may be considered as an important mediator in the
      regulation of breast cancer progression. 

PMID- 24105682
TI  - In vitro screening of selected feed additives, plant essential oils and plant
      extracts for rumen methane mitigation.
AB  - BACKGROUND: Ruminants produce large quantities of methane in their rumen as a by
      product of microbial digestion of feed. Antibiotics are added to ruminant feed to
      reduce wasteful production of methane; however, this practice has some downsides.
      A search for safer and natural feed additives with anti-methanogenic properties
      is under way. The objective of this research was to examine selected feed
      additives, plant essential oils and plant extracts for their anti-methanogenic
      potential in the rumen using an in vitro batch fermentation system. RESULTS: A
      significant reduction (P < 0.05) in methane production was observed with nine
      feed additives (up to 40% reduction), all eight essential oils (up to 75%
      reduction) and two plant extracts (14% reduction) when compared to their
      respective controls. Amongst these, only an algal meal high in docosahexaenoic
      acid, preparations of Nannochloropsis oculata, calcareous marine algae, yeast
      metabolites and two tannins did not inhibit microbial gas and volatile acid
      production. CONCLUSIONS: The current study identified some potent dietary
      ingredients or plant compounds that can assist in developing novel feed additives
      for methane mitigation from the rumen.

PMID- 24105683
TI  - In reference to What is the role of tympanostomy tubes in the treatment of
      recurrent acute otitis media?

PMID- 24105684
TI  - Biomarkers of drugs targeting HER-family signalling in cancer.
AB  - The epidermal growth factor receptor family (EGFR/HER) is frequently deregulated
      in human cancers. Several aberrations at various levels have been successfully
      exploited as targets for anti-cancer therapies. However, with very few
      exceptions, drugs targeting HER signalling have shown only modest activity when
      used alone in cancers where a HER-related target can be identified. Optimization
      of the use of these drugs either alone or in combination with other anti-cancer
      agents would require a more precise definition of alterations that could predict
      for activity or resistance. Clinical validation of the several potential
      biomarkers emerging from clinical and translational studies is a challenging
      process. Thanks to combined efforts, collection of tumour tissues and other
      potentially relevant patients' materials has become more and more frequently
      mandatory in prospective studies with biologically targeted therapies. As a
      consequence, information on the value of promising biomarkers of drugs targeting
      HER-family receptor targeting is becoming available. This review will focus on
      breast cancer, where the HER2 subset has been the subject of a major research
      effort in the last two decades, and on gastric cancer, where HER2 targeting has
      emerged recently as a successful strategy.

PMID- 24105685
TI  - Congenital abdominal aortic aneurysm.

PMID- 24105686
TI  - A highly K(+)-selective phenylaza-[18]crown-6-lariat-ether-based fluoroionophore
      and its application in the sensing of K+ ions with an optical sensor film and in
      cells.
AB  - Herein, we report the synthesis of two phenylaza-[18]crown-6 lariat ethers with a
      coumarin fluorophore (1 and 2) and we reveal that compound 1 is an excellent
      probe for K(+) ions under simulated physiological conditions. The presence of a 2
      methoxyethoxy lariat group at the ortho position of the anilino moiety is crucial
      to the substantially increased stability of compounds 1 and 2 over their lariat
      free phenylaza-[18]crown-6 ether analogues. Probe 1 shows a high K(+)/Na(+)
      selectivity and a 2.5-fold fluorescence enhancement was observed in the presence
      of 100 mM K(+) ions. A fluorescent membrane sensor, which was prepared by
      incorporating probe 1 into a hydrogel, showed a fully reversible response, a
      response time of 150 s, and a signal change of 7.8% per 1 mM K(+) within the
      range 1-10 mM K(+). The membrane was easily fabricated (only a single sensing
      layer on a solid polyester support), yet no leaching was observed. Moreover,
      compound 1 rapidly permeated into cells, was cytocompatible, and was suitable for
      the fluorescent imaging of K(+) ions on both the extracellular and intracellular
      levels.

PMID- 24105687
TI  - 25th anniversary article: a decade of organic/polymeric photovoltaic research.
AB  - Organic photovoltaic (OPV) technology has been developed and improved from a
      fancy concept with less than 1% power conversion efficiency (PCE) to over 10%
      PCE, particularly through the efforts in the last decade. The significant
      progress is the result of multidisciplinary research ranging from chemistry,
      material science, physics, and engineering. These efforts include the design and
      synthesis of novel compounds, understanding and controlling the film morphology,
      elucidating the device mechanisms, developing new device architectures, and
      improving large-scale manufacture. All of these achievements catalyzed the rapid
      growth of the OPV technology. This review article takes a retrospective look at
      the research and development of OPV, and focuses on recent advances of solution
      processed materials and devices during the last decade, particular the polymer
      version of the materials and devices. The work in this field is exciting and OPV
      technology is a promising candidate for future thin film solar cells. 

PMID- 24105688
TI  - Contribution of ATM and FOXE1 (TTF2) to risk of papillary thyroid carcinoma in
      Belarusian children exposed to radiation.
AB  - A dramatic increase in the incidence of papillary thyroid carcinoma (PTC) after
      childhood exposure to ionizing radiation from the Chernobyl nuclear accident has
      been described as the largest number of tumors of one type due to one cause that
      have ever occurred. inter-individual variations in response to radiation have
      been documented and the role of genetics in sporadic PTC is well established,
      suggesting that genetic factors may also affect the risk of radiation-related
      PTC. To investigate how environmental and host factors interplay to modify PTC
      risk, we genotyped 83 cases and 324 matched controls sampled from children living
      in the area contaminated by fallout from the Chernobyl power plant accident for
      19 polymorphisms previously associated with PTC, thyroid biology or radiation
      induced second primary tumors. Significant association with PTC was found for
      rs1801516 (D1853N) in ATM (odds ratio (OR) = 0.34, 95% confidence interval (CI)
      0.16, 0.73) and rs1867277 in the promoter region of FOXE1 (OR = 1.55, 95% CI
      1.03, 2.34). Analysis of additional polymorphisms confirmed the association
      between these two genes and PTC. Our findings suggest that both DNA double-strand
      break repair pathway and thyroid morphogenesis pathway or dysregulation of
      thyroid differentiated state maintenance are involved in the etiology of PTC, and
      that the studied genetic polymorphisms and radiation dose appear to act as
      independent multiplicative risk factors for PTC. 

PMID- 24105689
TI  - Evolution of enterohemorrhagic escherichia coli O26 based on single-nucleotide
      polymorphisms.
AB  - Enterohemorrhagic Escherichia coli (EHEC) O26:H11/H- is the predominant non-O157
      EHEC serotype among patients with diarrhea, bloody diarrhea, and hemolytic uremic
      syndrome (HUS) worldwide. To elucidate their phylogeny and association between
      their phylogenetic background and clinical outcome of the infection, we
      investigated 120 EHEC O26:H11/H- strains isolated between 1965 and 2012 from
      asymptomatic carriers and patients with diarrhea or HUS. Whole-genome shotgun
      sequencing (WGS) was applied to ten representative EHEC O26 isolates to determine
      single nucleotide polymorphism (SNP) localizations within a predefined set of
      core genes. A multiplex SNP assay, comprising a randomly distributed subset of 48
      SNPs, was established to detect SNPs in 110 additional EHEC O26 strains. Within
      approximately 1 Mb of core genes, WGS resulted in 476 high-quality bi-allelic SNP
      localizations. Forty-eight of these were subsequently investigated in 110 EHEC
      O26 and four different SNP clonal complexes (SNP-CC) were identified. SNP-CC2 was
      significantly associated with the development of HUS. Within the subsequently
      established evolutionary model of EHEC O26, we dated the emergence of human EHEC
      O26 to approximately 19,700 years ago and demonstrated a recent evolution within
      humans into the 4 SNP-CCs over the past 1,650 years. WGS and subsequent SNP
      typing enabled us to gain new insights into the evolution of EHEC O26 suggesting
      a common theme in this EHEC group with analogies to EHEC O157. In addition, the
      SNP-CC analysis may help to assess a risk in infected individuals for the
      progression to HUS and to implement more specific infection control measures.

PMID- 24105690
TI  - Are prophylactic antibiotics useful in the management of facial fractures?

PMID- 24105691
TI  - What is the role of imaging in tinnitus?

PMID- 24105693
TI  - Cerebral blood flow quantification in swine using pseudo-continuous arterial spin
      labeling.
AB  - PURPOSE: To develop quantitative cerebral blood flow (CBF) imaging using pseudo
      continuous arterial spin labeling (PCASL) in swine, accounting for their
      cerebrovascular anatomy and physiology. MATERIALS AND METHODS: Five domestic pigs
      (2.5-3 months, 25 kg) were used in these studies. The orientation of the labeled
      arteries, T1bl , M0bl , and T1gm were measured in swine. Labeling parameters were
      tuned with respect to blood velocity to optimize labeling efficiency based on the
      data collected from three subjects. Finally, CBF and arterial transit time (ATT)
      maps for two subjects were created from PCASL data to determine global averages.
      RESULTS: The average labeling efficiency over measured velocities of 5-18 cm/s
      was 0.930. The average T1bl was 1546 ms, the average T1gm was 1224 ms, and the
      average blood-to-white matter ratio of M0 was 1.25, which was used to find M0bl .
      The global averages over the subjects were 54.05 mL/100 g tissue/min CBF and 1261
      ms ATT. CONCLUSION: This study demonstrates the feasibility of PCASL for CBF
      quantification in swine. Quantification of CBF using PCASL in swine can be
      further developed as an accessible and cost-effective model of human cerebral
      perfusion for investigating injuries that affect blood flow.

PMID- 24105692
TI  - The mannose receptor is expressed by olfactory ensheathing cells in the rat
      olfactory bulb.
AB  - Complex carbohydrate structures are essential molecules of infectious bacteria,
      parasites, and host cells and are involved in cell signaling associated with
      immune responses, glycoprotein homeostasis, and cell migration. The uptake of
      mannose-tailed glycans is usually carried out by professional phagocytes to
      trigger MHC class I- and MHC class II-restricted antigen presentation or,
      alternatively, to end inflammation. We have detected the mannose receptor (MR) in
      cultured olfactory ensheathing cells (OECs), so we investigated by flow cytometry
      whether recently dissociated cells of the olfactory bulb (OB) nerve fiber layer
      (ONL) could bind a mannosylated ligand (fluorescein conjugate of mannosyl bovine
      serum albumin; Man/BSA-FITC) in a specific manner. In addition, we estimated the
      relative proportion of ONL OECs, microglia, and astrocytes, tagged by 2'3'-cyclic
      nucleotide 3'-phosphodiesterase (CNPase), by the B4 isolectin of Griffonia
      simplicifonia (IB4), and by glial fibrillary acidic protein (GFAP), respectively,
      that were Man/BSA-FITC(+) . We also determined by histochemistry and/or
      immunohistochemistry whether Man/BSA-FITC or an anti-MR antibody (anti-C-terminal
      MR peptide; anti-cMR) labeled OECs and/or parenchymal microglia. In addition, we
      confirmed by Western blot with the K1K2 (against the entire MR molecule) antibody
      that a band of about 180 kDA is expressed in the OB. Our findings are compatible
      with a prospective sentinel role of OECs against pathogens of the upper airways
      and/or damage-associated glycidic patterns as well as with homeostasis of OB
      mannosylated glycoproteins.

PMID- 24105694
TI  - Tolerability and efficacy of pegylated interferon-alpha-2a in combination with
      imatinib for patients with chronic-phase chronic myeloid leukemia.
AB  - BACKGROUND: The pegylated form of interferon-alpha-2a (PegIFNa2a) in combination
      with imatinib has demonstrated a molecular improvement in patients with chronic
      phase chronic myeloid leukemia. However, to the authors' knowledge, the
      appropriate dose of PegIFNa2a has not been established to date. METHODS: In the
      French SPIRIT trial, the authors compared 2 initial doses of PegIFNa2a, taking
      into account an amendment that recommended reducing that dose from 90 MUg/week to
      45 MUg/week because of toxicities. Accordingly, 2 subgroups of patients were
      identified: the PegIFN90 group (171 patients who were treated with the 90
      MUg/week dose) and the PegIFN45 group (50 patients who were treated with the 45
      MUg/week dose). Both groups were compared for toxicity and efficacy. RESULTS:
      PegIFNa2a at a dose of 90 MUg/week resulted in a rate of 54% of grade 3 to 4
      hematologic toxicity compared with 27% with the dose of 45 MUg/week (P < .001),
      leading to discontinuation rates of 40% and 10%, respectively, before 6 months.
      The dose reduction did not significantly affect the efficacy of the combination.
      By 12 months, the cumulative molecular response rates (ie, BCR-ABL/abl <= 0.01
      [IS: molecular responses graded as molecular response 4 (MR4)]) were 14% and 25%,
      respectively, for the subgroup treated with imatinib at a dose of 400 mg and the
      PegIFN90 subgroup. After the amendment, the MR4 rates were 10% and 28%,
      respectively, for the subgroup treated with imatinib at the 400-mg dose and
      PegIFN45 subgroup (P < .0001). CONCLUSIONS: The results of the current study
      demonstrate that in combination with imatinib, the efficient dose of PegIFNa2a
      appears to be 45 MUg/week. Society.

PMID- 24105695
TI  - Single-electron-transfer (SET)-induced oxidative biaryl coupling by
      polyalkoxybenzene-derived diaryliodonium(III) salts.
AB  - Metal-free oxidative C-C coupling by using polyalkoxybenzene-derived
      diaryliodonium(III) salts as both the oxidant and aryl source has been developed.
      These salts can induce single-electron-transfer (SET) oxidation to yield electron
      rich arenes and subsequently transfer the polyalkoxyphenyl group into in situ
      generated aromatic radical cations to produce biaryl products. The reaction is
      promoted by a Lewis acid that activates the iodonium salts. It has been revealed
      that the reactivity of the salts under acidic conditions is quite different to
      their known behavior under basic conditions. The reactivity preference of a
      series of iodonium salts in the SET oxidation and their ligand transfer abilities
      have been systematically investigated and the results are summarized in this
      report.

PMID- 24105696
TI  - Examining associations between adolescent binge eating and binge eating in
      parents and friends.
AB  - OBJECTIVE: Binge eating is prevalent among adolescents, but little is known about
      how parents and friends may influence such behaviors. This study examined
      associations between adolescent binge eating behaviors, and similar behaviors in
      their parents and friends. METHOD: Participants were 2,770 target adolescent boys
      and girls who had at least one friend and/or parent who also participated.
      Logistic regression, stratified by gender, examined associations between parents'
      and friends' self-reported binge eating, and similar behaviors in target
      adolescents. RESULTS: Girls' binge eating was associated with their male friends'
      (odds ratio = 2.33; p = 0.03) and fathers' binge eating (odds ratio = 3.38; p =
      0.02), but not with their female friends' or mothers' binge eating (p > 0.05).
      For boys, binge eating was not associated with parents' or friends' behavior.
      DISCUSSION: Adolescent girls' binge eating is associated with similar behaviors
      in their other-sex parents and friends. Results should be replicated, and
      mechanisms explaining this relation should be further explored.

PMID- 24105698
TI  - Life after perinatal stroke.

PMID- 24105697
TI  - Intraoperative magnesium administration does not improve neurocognitive function
      after cardiac surgery.
AB  - BACKGROUND AND PURPOSE: Neurocognitive decline occurs frequently after cardiac
      surgery and persists in a significant number of patients. Magnesium is thought to
      provide neuroprotection by preservation of cellular energy metabolism, blockade
      of the N-methyl-D-aspartate receptor, diminution of the inflammatory response,
      and inhibition of platelet activation. We therefore hypothesized that
      intraoperative magnesium administration would decrease postoperative cognitive
      impairment. METHODS: After approval by the Duke University Health System
      Institutional Review Board, 389 patients undergoing cardiac surgery were enrolled
      in this prospective, randomized, double-blind, placebo-controlled clinical trial.
      Subjects were randomized to receive magnesium as a 50 mg/kg bolus followed by
      another 50 mg/kg infusion for 3 hours or placebo bolus and infusion. Cognitive
      function was assessed preoperatively and again at 6 weeks postoperatively using a
      standardized test battery. Mean CD11b fluorescence and percentage of platelets
      expressing CD62P, which are markers of leukocyte and platelet activation,
      respectively, were assessed by flow cytometry as a secondary outcome. The effect
      of magnesium on postoperative cognition was tested using multivariable regression
      modeling, adjusting for age, years of education, baseline cognition, sex, race,
      and weight. RESULTS: Among the 389 allocated subjects (magnesium: n=198; placebo:
      n=191), the incidence of cognitive deficit in the magnesium group was 44.4%
      compared with 44.9% in the placebo group (P=0.93). The cognitive change score and
      platelet and leukocyte activation were also not different between the groups.
      Multivariable analysis revealed a marginal interaction between treatment group
      and weight such that heavier subjects receiving magnesium were less likely to
      have cognitive deficit (P=0.06). CONCLUSIONS: Magnesium administered
      intravenously during cardiac surgery does not reduce postoperative cognitive
      dysfunction. CLINICAL TRIAL REGISTRATION URL: http://www.clinicaltrials.gov.
      Unique identifier: NCT00041392.

PMID- 24105699
TI  - Clot length distribution and predictors in anterior circulation stroke:
      implications for intra-arterial therapy.
AB  - BACKGROUND AND PURPOSE: Thin-section noncontrast computed tomography images can
      be used to measure hyperdense clot length in acute ischemic stroke. Clots>=8 mm
      have a very low probability of intravenous tissue-type plasminogen activator
      recanalization and hence may benefit from a bridging intra-arterial approach. To
      understand the prevalence of such clots, we sought to determine the distribution
      and predictors of clot lengths in consecutive anterior circulation proximal
      artery occlusions. METHODS: Of 623 consecutive patients with acute ischemic
      stroke, 53 met inclusion criteria: presentation<8 hours from onset; intracranial
      internal carotid artery-terminus or proximal-middle cerebral artery occlusion;
      admission thin-slice noncontrast computed tomography (<=2.5 mm); and no
      intravenous tissue-type plasminogen activator pretreatment. For each patient,
      hyperdense clot length was measured and recorded along with additional relevant
      imaging and clinical data. RESULTS: Mean age was 70 years, and mean time to
      computed tomography was 213 minutes. Median baseline National Institutes of
      Health Stroke Scale was 16.5. Occlusions were located in the internal carotid
      artery-terminus (34% [18 of 53]), middle cerebral artery M1 (49% [26 of 53]) and
      M2 segments (17% [9 of 53]). Hyperdense thrombus was visible in 96%, with mean
      and median clot lengths (mm) of 18.5 (+/-14.2) and 16.1 (7.6-25.2), respectively.
      Occlusion location was the strongest predictor of clot length (multivariate,
      P=0.02). Clot length was >=8 mm in 94%, 73%, and 22% of internal carotid artery
      terminus, M1, and M2 occlusions, respectively. CONCLUSIONS: The majority of
      anterior circulation proximal occlusions are >=8 mm long, helping to explain the
      low published rates of intravenous tissue-type plasminogen activator
      recanalization. Internal carotid artery-terminus occlusion is an excellent marker
      for clot length>=8 mm; vessel-imaging status alone may be sufficient. Thin
      section noncontrast computed tomography seems useful for patients with middle
      cerebral artery occlusion because of the wide variability of clot lengths.

PMID- 24105700
TI  - Intracerebral hematomas disappear on T2*-weighted images during normobaric oxygen
      therapy.
AB  - BACKGROUND AND PURPOSE: The aim of the present study was to investigate the
      effects of normobaric oxygen (NBO) therapy on T2*-weighted images of intracranial
      hemorrhages (ICHs). METHODS: Two common models of ICH were performed in mice, and
      longitudinal T2*-weighted images of the hematomas were acquired under normoxia or
      NBO. The effects of NBO were also investigated on perfusion-weighted imaging,
      susceptibility-weighted imaging, and molecular imaging of vascular cell adhesion
      molecule-1 after ICH. Last, we performed neurological testing, including
      neuroscore, actimetry, and gait analysis (Catwalk), to study the influence of NBO
      on neurological outcome of mice presenting ICH. RESULTS: Our results demonstrated
      that NBO, even during a short period of time, dramatically reduces the
      sensitivity of T2*-weighted imaging to detect ICH. Moreover, we provide evidence
      that the disappearance of ICH on T2*-weighted imaging could be used to improve
      accuracy of perfusion-weighted imaging and to allow molecular imaging after ICH.
      Importantly, a 30-minute NBO preparation 24 hours after ICH onset does not
      influence neurological outcome. CONCLUSIONS: We provide an experimental
      demonstration that NBO significantly affects T2*-weighted imaging in ICH.
      Although this phenomenon could lead to inaccurate assessment of ICH volume, it
      could also be safely used to allow perfusion-weighted imaging and molecular
      imaging.

PMID- 24105701
TI  - Impact of emergency medical services stroke routing protocols on Primary Stroke
      Center certification in California.
AB  - BACKGROUND AND PURPOSE: Organized stroke systems of care include Primary Stroke
      Center (PSC) certification and preferential emergency medical services (EMS)
      routing of suspected patients with stroke to designated PSCs. Stroke EMS routing
      is not nationally governed; in California, routing is determined by county. EMS
      routing policies might provide an incentive for PSC accreditation. We evaluated
      the relationship between independent adoption of EMS routing protocols and PSC
      designation acquisition in California. METHODS: Dates of PSC certification were
      obtained through The Joint Commissions Website and confirmatory calls to stroke
      coordinators. Starting date of county EMS PSC routing policies was obtained from
      county EMS agencies. We provide descriptive analysis of number of hospitals
      achieving PSC designation relative to implementation of EMS routing policies for
      all counties with PSCs. RESULTS: By June 2012, there were 131 California PSCs in
      27 counties, and 22 of 58 counties had implemented EMS routing policies. The
      greatest number of PSCs was in Los Angeles (30) followed by San Diego (11),
      Orange (9), and Santa Clara (9) counties. Achievement of PSC designation occurred
      more frequently immediately before and after EMS routing: 51 PSCs (39%) within 1
      year; 85 PSCs (65%) within 2 years. The yearly rate of eligible hospital
      conversion to PSC designation accelerated concurrent with EMS diversion policy
      adoption from 3.8% before to 16.2% during and decelerated afterward to 7.6%.
      CONCLUSIONS: Implementation of EMS routing policies may be an important factor
      driving PSC certification. National adoption of stroke routing policies may lead
      to more PSCs, positively impacting patient care.

PMID- 24105702
TI  - Whole-exome sequencing identifies a variant of the mitochondrial MT-ND1 gene
      associated with epileptic encephalopathy: west syndrome evolving to Lennox
      Gastaut syndrome.
AB  - We describe a West syndrome (WS) patient with unidentified etiology that evolved
      to Lennox-Gastaut syndrome. The mitochondrial respiratory chain of the patient
      showed a simple complex I deficiency in fibroblasts. Whole-exome sequencing (WES)
      uncovered two heterozygous mutations in NDUFV2 gene that were reassigned to a
      pseudogene. With the WES data, it was possible to obtain whole mitochondrial DNA
      sequencing and to identify a heteroplasmic variant in the MT-ND1 (MTND1) gene
      (m.3946G>A, p.E214K). The expression of the gene in patient fibroblasts was not
      affected but the protein level was significantly reduced, suggesting that protein
      stability was affected by this mutation. The lower protein level also affected
      assembly of complex I and supercomplexes (I/III2 /IV and I/III2 ), leading to
      complex I deficiency. While ATP levels at steady state under stress conditions
      were not affected, the amount of ROS produced by complex I was significantly
      increased. 

PMID- 24105703
TI  - Titanium nitride nanocrystals on nitrogen-doped graphene as an efficient
      electrocatalyst for oxygen reduction reaction.

PMID- 24105704
TI  - Chemical composition and antioxidant properties of Laurus nobilis L. and Myrtus
      communis L. essential oils from Morocco and evaluation of their antimicrobial
      activity acting alone or in combined processes for food preservation.
AB  - BACKGROUND: This study describes the antioxidant and antimicrobial activity of
      Laurus nobilis L. and Myrtus communis L. essential oils (EOs). This is the first
      report of the synergistic antimicrobial effect of these EOs in combination with
      physical food preservation treatments. RESULTS: EOs obtained by steam
      distillation from aerial parts of Laurus nobilis and Myrtus communis were
      analysed by using gas chromatography-mass spectrometry. The main compounds were
      1,8-cineole and 2-carene (L. nobilis EO); and myrtenyl acetate, 1,8-cineole and
      alpha-pinene (M. communis EO). L. nobilis EO showed higher antioxidant activity
      than M. communis EO in three complementary antioxidant tests. Although
      antimicrobial activity tests demonstrated the effectiveness of L. nobilis EO and
      the lack of bactericidal effect of M. communis EO, synergistic lethal effects
      were observed when combining each EO (0.2 uL mL(-1)) with mild heat (54 degrees C
      for 10 min) or high hydrostatic pressure (175-400 MPa for 20 min). In contrast,
      combination of EOs with pulsed electric fields (30 kV cm(-1) for 25 pulses)
      showed no additional effects. CONCLUSION: This study shows the great potential of
      these EOs in combined treatments with mild heat and high hydrostatic pressure to
      obtain a higher inactivation of foodborne pathogens, which might help in the
      design of safe processes applied at low intensity.

PMID- 24105705
TI  - Sonographic prediction of vaginal delivery in prolonged labor: a two-center
      study.
AB  - OBJECTIVE: To investigate whether head-perineum distance (HPD) measured by
      transperineal ultrasound is predictive of vaginal delivery and time remaining in
      labor in nulliparous women with prolonged first stage of labor and to compare the
      predictive value with that of angle of progression (AoP). METHODS: This was a
      prospective observational study at Stavanger University Hospital, Norway and
      Addenbrooke's Hospital, Cambridge, UK from January 2012 to April 2013, of
      nulliparous women with singleton pregnancies with cephalic presentation at term
      with prolonged first stage of labor. We used transperineal ultrasound to measure
      HPD (shortest distance between the outer bony limit of the fetal skull and the
      perineum) and AoP (angle between a line through the long axis of the symphysis
      and the tangent to the fetal head) and transabdominal ultrasound to classify
      fetal head position. The main outcomes were vaginal delivery and time remaining
      in labor. RESULTS: Of 150 women enrolled, 39 underwent delivery by Cesarean
      section. The area under the receiver-operating characteristics curve for the
      prediction of vaginal delivery was 81% (95% CI, 73-89%) using HPD as the test
      variable and 72% (95% CI, 63-82%) using AoP. HPD was <= 40 mm in 84 (56%) women,
      of whom 77 (92%; 95% CI, 84-96%) delivered vaginally. HPD was > 40 mm in the
      other 66 (44%) women, of whom 34 (52%; 95% CI, 40-63%) delivered vaginally. AoP
      was >= 110 degrees  in 84 of the 145 (58%) in whom this was available and, of
      these, 74 (88%; 95% CI, 79-93%) delivered vaginally. AoP was < 110 degrees  in
      the other 61 (42%) women, of whom 35 (57%; 95% CI, 45-69%) delivered vaginally.
      Multivariable logistic regression analysis showed that HPD <= 40 mm (odds ratio
      (OR), 4.92; 95% CI, 1.54-15.80), AoP >= 110 degrees  (OR, 3.11; 95% CI, 1.01
      9.56), non-occiput posterior position (OR, 3.36; 95% CI, 1.24-9.12) and
      spontaneous onset of labor (OR, 4.44; 95% CI, 1.42-13.89) were independent
      predictors for vaginal delivery. Both ultrasound methods were predictive for the
      time remaining in labor. CONCLUSION: Transperineal ultrasound measurement of HPD
      and AoP provide important information about the likelihood of vaginal delivery
      and the time remaining in labor in nulliparous women with prolonged labor.

PMID- 24105706
TI  - Short KR-12 analogs designed from human cathelicidin LL-37 possessing both
      antimicrobial and antiendotoxic activities without mammalian cell toxicity.
AB  - KR-12 (residues 18-29 of LL-37) was known to be the smallest peptide of human
      cathelicidin LL-37 possessing antimicrobial activity. In order to optimize alpha
      helical short antimicrobial peptides having both antimicrobial and antiendotoxic
      activities without mammalian cell toxicity, we designed and synthesized a series
      of KR-12 analogs. Highest hydrophobic analogs KR-12-a5 and KR-12-a6 displayed
      greater inhibition of lipopolysaccharide (LPS)-stimulated tumor necrosis factor
      alpha production and higher LPS-binding activity. We have observed that
      antimicrobial activity is independent of charge, but LPS neutralization requires
      a balance of hydrophobicity and net positive charge. Among KR-12 analogs, KR-12
      a2, KR-12-a3 and KR-12-a4 showed much higher cell specificity for bacteria over
      erythrocytes and retained antiendotoxic activity, relative to parental LL-37. KR
      12-a5 displayed the strongest antiendotoxic activity but almost similar cell
      specificity as compared with LL-37. Also, these KR-12 analogs (KR-12-a2, KR-12
      a3, KR-12-a4 and KR-12-a5) exhibited potent antimicrobial activity (minimal
      inhibitory concentration: 4 MUM) against methicillin-resistant Staphylococcus
      aureus. Taken together, these KR-12 analogs have the potential for future
      development as a novel class of antimicrobial and anti-inflammatory therapeutic
      agents.

PMID- 24105707
TI  - A radioanatomic study of the internal mammary artery and its perforators using
      multidetector computed tomography angiography.
AB  - The Internal Mammary Artery (IMA) and its perforators play an important role in
      coronary bypass grafting and reconstructive breast, head, and neck surgery. This
      study aimed to obtain anatomic data pertaining to these vessels using Multi
      Detector Computed Tomography Angiography (MDCTA) and to demonstrate that the
      MDCTA could be a considerable assessment tool prior to surgery. In 50 outpatients
      (27 males and 23 females), the above-mentioned arteries were bilaterally
      evaluated with a 16-detector spiral computed tomography scanner. Based on the
      obtained images, diameters of the bilateral IMAs were separately measured in each
      intercostal spaces from 1 to 5 through their traces. IMAPs greater than 0.5 mm in
      diameter were bilaterally evaluated in terms of distance from the sternal border
      to the ramification point under the muscular layer, maximal external diameter at
      ramification from the IMA, and the length between the ramification point from the
      IMA and enter point to the subcutaneous fat tissue. Mean diameters of the left
      and right IMAs were 2.05 +/- 0.50 mm and 2.20 +/- 0.57 mm, respectively. Mean
      diameters, distances, and lengths of the perforators were 1.30 +/- 0.30 mm, 6.80
      +/- 3.40 mm, 17.05 +/- 6.07 mm on the left side and 1.32 +/- 0.25 mm, 6.71 +/-
      3.43 mm, 17.35 +/- 3.48 mm on the right side, respectively. No statistically
      difference was found between the sides (P > 0.05). About 20 of 36 perforators
      appeared in the second intercostal space, whereas there were eight in the first
      and eight in the third intercostal space. MDCTA, as a non-invasive vascular
      imaging method, can be a valuable tool for investigating the anatomic
      characteristics of the IMA and its perforators before planning an operation.

PMID- 24105708
TI  - High-performance oxygen reduction electrocatalysts based on cheap carbon black,
      nitrogen, and trace iron.
AB  - A real optimal Fe content: For N and Fe co-doped carbon electrocatalysts for
      oxygen reduction reactions (ORRs) it is found that there is a real optimal trace
      Fe content (Peak II), which has never been observed before. The real optimal
      electrocatalyst shows superior high activity for ORR and possesses the best
      price/performance ratio ever. 

PMID- 24105709
TI  - Effects of combined radiofrequency radiation exposure on levels of reactive
      oxygen species in neuronal cells.
AB  - The objective of this study was to investigate the effects of the combined RF
      radiation (837 MHz CDMA plus 1950 MHz WCDMA) signal on levels of intracellular
      reactive oxygen species (ROS) in neuronal cells. Exposure of the combined RF
      signal was conducted at specific absorption rate values of 2 W/kg of CDMA plus 2
      W/kg of WCDMA for 2 h. Co-exposure to combined RF radiation with either H2O2 or
      menadione was also performed. The experimental exposure groups were incubator
      control, sham-exposed, combined RF radiation-exposed with or without either H2O2
      or menadione groups. The intracellular ROS level was measured by flow cytometry
      using the fluorescent probe dichlorofluorescein diacetate. Intracellular ROS
      levels were not consistently affected by combined RF radiation exposure alone in
      a time-dependent manner in U87, PC12 or SH-SY5Y cells. In neuronal cells exposed
      to combined RF radiation with either H2O2 or menadione, intracellular ROS levels
      showed no statically significant alteration compared with exposure to menadione
      or H2O2 alone. These findings indicate that neither combined RF radiation alone
      nor combined RF radiation with menadione or H2O2 influences the intracellular ROS
      level in neuronal cells such as U87, PC12 or SH-SY5Y. 

PMID- 24105710
TI  - Can the two mechanisms of tumor cell killing by radiation be exploited for
      therapeutic gain?
AB  - The radiation killing of tumor cells by ionizing radiation is best described by
      the linear-quadratic (LQ) model. Research into the underlying mechanisms of alpha
      and beta-inactivation has suggested that different molecular targets (DNA in
      different forms) and different microdosimetric energy deposits (spurs versus
      electron track-ends) are involved. Clinical protocols with fractionated doses of
      about 2.0 Gy/day were defined empirically, and we now know that they produce
      cancer cures mainly by the alpha-inactivation mechanism. Radiobiology studies
      indicate that alpha and beta mechanisms exhibit widely different characteristics
      that should be addressed upfront as clinical fractionation schemes are altered.
      As radiation treatments attempt to exploit the advantages of larger dose
      fractions over shorter treatment times, the LQ model can be used to predict iso
      effective tumor cell killing and possibly iso-effective normal tissue
      complications. Linking best estimates of radiobiology and tumor biology
      parameters with tumor control probability (TCP) and normal tissue complication
      probability (NTCP) models will enable us to improve and optimize cancer treatment
      protocols, delivering no more fractions than are strictly necessary for a high
      therapeutic ratio. 

PMID- 24105711
TI  - 125Iodine monotherapy for Japanese men with low- and intermediate-risk prostate
      cancer: outcomes after 5 years of follow-up.
AB  - Data from 305 Japanese men with low-risk (n = 175) or intermediate-risk (n = 130)
      prostate cancer who underwent (125)I monotherapy were retrospectively analyzed.
      Of the 305 patients, 93 received hormonal therapy for a median of 6 months
      (range, 1-33 months) before implantation. The prescribed dose to the prostate
      plus 3- to 5-mm margin was set at 145 Gy. The mean dose to 90% of the prostate
      volume at 1 month (D90) and the prostate volume receiving at least 100% dose at 1
      month (V100) were 173.4 Gy and 95.8%, respectively. The median follow-up was 66
      months (range, 12-94 months). The 5-year biochemical non-evidence of disease rate
      was 95.5% (low-risk, 94.2%; intermediate-risk, 97.3%). The 5-year freedom from
      clinical failure rate was 98.9% (low-risk, 98.9%; intermediate-risk, 99.2%).The
      initial prostate-specific antigen level was identified as a significant
      predictive factor for biochemical recurrence (P = 0.029). The late Grade 3
      genitourinary toxicity rate was 2.0%. No patients displayed late gastrointestinal
      toxicity of Grade 3 or worse. Monotherapy with (125)I showed excellent outcomes
      with limited morbidity for Japanese men with low- and intermediate-risk prostate
      cancer after 5 years of follow-up. 

PMID- 24105712
TI  - Simvastatin attenuates radiation-induced tissue damage in mice.
AB  - The aim of this study was to investigate the protective effect of simvastatin
      against radiation-induced tissue injury in mice. Mice were radiated with 4 Gy or
      8 Gy after 20 mg/kg/d simvastatin treatment over 2 weeks. Morphological changes
      were observed in the jejunum and bone marrow, and apoptotic cells were determined
      in both tissues. Peripheral blood cells were counted, and the superoxide
      dismutase (SOD) activity and the malondialdehyde (MDA) level in tissues of both
      thymus and spleen were measured. Compared with the radiation-only group, 20
      mg/kg/d simvastatin administration significantly increased the mean villi height
      and decreased apoptotic cells in jejunum tissue, and stimulated regeneration and
      reduced apoptotic cells in bone marrow. Peripheral blood cell analysis revealed
      that simvastatin treatment induced a larger number of red blood cells and
      increased the hemoglobin level present after 4 Gy of radiation. Interestingly, it
      was also found that the number of peripheral endothelial progenitor cells was
      markedly increased following simvastatin administration. Antioxidant
      determination for tissues displayed that simvastatin therapy increased the SOD
      activity after both 4 and 8 Gy of radiation, but only decreased the MDA level
      after 4 Gy. Simvastatin ameliorated radiation-induced tissue damage in mice. The
      radioprotective effect of simvastatin was possibly related to inhibition of
      apoptosis and improvement of oxygen-carrying and antioxidant activities. 

PMID- 24105713
TI  - When is immediate surgical intervention required for isolated orbital blowout
      fractures?

PMID- 24105714
TI  - Gastric cancer progression may involve a shift in HLA-E profile from an intact
      heterodimer to beta2-microglobulin-free monomer.
AB  - Phenotypic expression of human leukocyte antigen (HLA)-E on the surface of tumor
      lesions includes intact heterodimer [HLA-E heavy chain and beta2-microglobulin
      (beta2m)] and beta2m-free monomer. Anti-HLA-E monoclonal antibodies (mAbs), MEM
      E/02 or 3D12 bind to the peptide sequences in beta2m-free HLA-E, which is common
      and shared with HLA-Ia monomers. A newly developed monospecific anti-HLA-E mAb
      (TFL-033) recognizes HLA-E-restricted peptide sequences on alpha1 and alpha2
      helices away from beta2-m-site. Tumor progression may involve shedding of beta2-m
      from HLA-E or overexpression of beta2m-free monomers. There is a need to identify
      and distinguish the different phenotypic expression of HLA-E, particularly the
      intact heterodimer from the beta2m-free monomer on the surface of tumor lesions.
      Because of the unique peptide-binding affinities of the mAbs, it is hypothesized
      that TFL-033 and MEM-E/02 may distinguish the phenotypic expressions of cell
      surface HLA-E during stages of tumor progression. Only TFL-033 stained diffusely
      the cytoplasm of normal mucosa. The incidence and intensity of TFL-033 staining
      of the cell surface in early stages, poorly or undifferentiated and non-nodal
      lesions and in diffuse carcinoma is greater than that of MEM-E/02. Whereas MEM
      E/02 stained terminal stages, adenocarcinoma and lymph node metastatic lesions
      intensely, either owing to increased expression of beta2m-free HLA-E with tumor
      progression or owing to expression of HLA-Ia molecules. Our study evaluates the
      relative diagnostic potential of HLA-E-monospecific TFL-033 and the HLA-Ia
      reactive MEM-E/02 for determining the specific distribution and immunodiagnosis
      of different phenotypic expression HLA-E in tumor lesions, and the structural and
      functional alterations undergone by HLA-E during tumor progression. 

PMID- 24105715
TI  - Conformational selection in glycomimetics: human galectin-1 only recognizes syn
      Psi-type conformations of beta-1,3-linked lactose and its C-glycosyl derivative.
AB  - The human lectin galectin-1 (hGal-1) translates sugar signals, that is, beta
      galactosides, into effects on the level of cells, for example, growth regulation,
      and has become a model for studying binding of biopharmaceutically relevant
      derivatives. Bound-state conformations of Galbeta-C-(1->3)-Glcbeta-OMe (1) and
      its betaGal-(1->3)-betaGlc-OMe disaccharide parent compound were studied by using
      NMR spectroscopy (transferred (TR)-NOESY data), assisted by docking experiments
      and molecular dynamics (MD) simulations. The molecular recognition process
      involves a conformational selection event. Although free C-glycoside access four
      distinct conformers in solution, hGal-1 recognizes shape of a local minimum of
      compound 1, the syn-Phi/syn-Psi conformer, not the structure at global minimum.
      MD simulations were run to explain, in structural terms, the observed geometry of
      the complex. 

PMID- 24105716
TI  - Influence of hydroxypropyl-Beta-cyclodextrin on the stability of dilute and
      highly concentrated immunoglobulin g formulations.
AB  - Antibody solutions usually require the addition of suitable excipients-such as
      surfactants and polyols-to overcome stability problems under mechanical or
      thermal stress. Because cyclodextrins exhibit weak surface activity (similar to
      surfactants) and a sugar-based structure (like polyols), they can, in principle,
      stabilize proteins by a double mechanism. Accordingly, the stabilizing potential
      of increasing concentrations of hydroxypropyl-beta-cyclodextrin (HPbetaCD) was
      investigated for two antibodies in dilute (1.8 mg/mL) and highly concentrated
      (100 mg/mL) solutions and compared with standard polysorbate 80 or sucrose
      formulations as controls. Formulations were stressed by stirring or elevated
      temperature, and stability was evaluated by monomer recovery using size-exclusion
      chromatography, turbidity, and light obscuration measurements. Results show that
      increasing HPbetaCD concentrations up to 100 mM lead to a gradual protein
      stabilization during stirring-irrespective of the protein concentration and
      unaffected by an increased viscosity. Storage at 50 degrees C induced a decrease
      of monomer recovery with increasing HPbetaCD concentrations, which was mirrored
      in differential scanning calorimetry measurements, where an increasing amount of
      HPbetaCD leads to a significant reduction of the protein melting temperature. In
      the light of previous results on protein stabilization by HPbetaCD, it is
      suggested that the stabilizing effects of HPbetaCD must be tested on a case-by
      case basis.

PMID- 24105717
TI  - Left atrial late gadolinium enhancement with water-fat separation: the importance
      of phase-encoding order.
AB  - PURPOSE: To compare two late gadolinium enhancement (LGE) cardiovascular magnetic
      resonance (CMR) methods: a Dixon LGE sequence with sequential phase-encoding
      order, reconstructed using water-fat separation, and standard fat-saturated LGE.
      MATERIALS AND METHODS: We implemented a dual-echo Dixon LGE method for
      reconstructing water-only images and compared it to fat-saturated LGE in 12
      patients prior to their first pulmonary vein isolation (PVI) procedure. Images
      were analyzed for quality and fat-suppression. Regions of the left atrium were
      evaluated by a blinded observer (1 = prominent enhancement, 0 = mild or absent
      enhancement) on two sets of images (fat-saturated and water-only LGE) and
      agreement was assessed. RESULTS: Water-only LGE showed a trend toward better fat
      suppression (P = 0.06), with a significantly more homogeneous blood pool signal
      and reduced inflow artifacts (both P < 0.01). Agreement between fat-saturated LGE
      and water-only methods was found in 84% of regions, significantly correlated by
      chi-squared test (P < 0.001). The kappa value was 0.52 (moderate). The average
      number of enhancing segments was higher for fat-saturated LGE than water-only LGE
      (4.2 +/- 2.7 vs. 3.2 +/- 2.9, P = 0.03). CONCLUSION: The two-point Dixon LGE
      technique reduces artifacts due to a centric k-space order. A similar enhancement
      pattern was observed irrespective of the LGE technique, with more enhancement
      detected by fat-saturated LGE.

PMID- 24105718
TI  - New heteronuclear bridged borylene complexes that were derived from [{Cp*CoCl}2]
      and mono-metal-carbonyl fragments.
AB  - The synthesis, structural characterization, and reactivity of new bridged
      borylene complexes are reported. The reaction of [{Cp*CoCl}2] with LiBH4.THF at 
      70  degrees C, followed by treatment with [M(CO)3(MeCN)3] (M=W, Mo, and Cr) under
      mild conditions, yielded heteronuclear triply bridged borylene complexes, [(MU3
      BH)(Cp*Co)2(MU-CO)M(CO)5] (1-3; 1: M=W, 2: M=Mo, 3: M=Cr). During the syntheses
      of complexes 1-3, capped-octahedral cluster [(Cp*Co)2(MU-H)(BH)4{Co(CO)2}] (4)
      was also isolated in good yield. Complexes 1-3 are isoelectronic and
      isostructural to [(MU3-BH)(Cp*RuCO)2(MU-CO){Fe(CO)3}] (5) and [(MU3
      BH)(Cp*RuCO)2(MU-H)(MU-CO){Mn(CO)3}] (6), with a trigonal-pyramidal geometry in
      which the MU3-BH ligand occupies the apical vertex. To test the reactivity of
      these borylene complexes towards bis-phosphine ligands, the room-temperature
      photolysis of complexes 1-3, 5, 6, and [{(MU3-BH)(Cp*Ru)Fe(CO)3}2(MU-CO)] (7) was
      carried out. Most of these complexes led to decomposition, although photolysis of
      complex 7 with [Ph2P(CH2)(n)PPh2] (n=1-3) yielded complexes 9-11, [3,4
      (Ph2P(CH2)(n)PPh2)-closo-1,2,3,4-Ru2Fe2(BH)2] (9: n=1, 10: n=2, 11: n=3). Quantum
      chemical calculations by using DFT methods were carried out on compounds 1-3 and
      9-11 and showed reasonable agreement with the experimentally obtained structural
      parameters, that is, large HOMO-LUMO gaps, in accordance with the high
      stabilities of these complexes, and NMR chemical shifts that accurately reflected
      the experimentally observed resonances. All of the new compounds were
      characterized in solution by using mass spectrometry, IR spectroscopy, and (1)H,
      (13)C, and (11)B NMR spectroscopy and their structural types were unequivocally
      established by crystallographic analysis of complexes 1, 2, 4, 9, and 10.

PMID- 24105721
TI  - Synthesis, antibacterial, and antiviral evaluation of new heterocycles containing
      the pyridine moiety.
AB  - A facile one-pot four-component reaction was utilized to construct 2-oxo-1,2
      dihydropyridine-3-carbonitrile as a scaffold for the synthesis of many fused
      heterocyclic systems, namely, furopyridine, pyridothiadiazepinthione, and
      pyridotriazine, as well as non-fused heterocyclic systems such as phthalazin
      2(1H)-ylnicotinonitrile, pyridin-2-yl-1H-pyrazole, and pyrazol-1-ylnicotino
      nitrile,1-(3-cyanopyridin-2-yl)-1H-pyrazole. The new compounds were evaluated as
      antimicrobial and antiviral agents. 

PMID- 24105720
TI  - Treatment trade-offs in myeloma: A survey of consecutive patients about
      contemporary maintenance strategies.
AB  - BACKGROUND: Two randomized trials have demonstrated improved progression-free
      survival (PFS) with lenalidomide maintenance after autologous transplantation for
      multiple myeloma (MM). Overall survival (OS) results are conflicting, and quality
      of-life (QOL) data are lacking. The authors conducted a systematic survey of
      patients with MM regarding what constitutes a meaningful benefit that would make
      burdens of maintenance treatments (toxicity and cost) acceptable. METHODS: A self
      administered survey was mailed to 1159 consecutive, living patients who were
      evaluated at Mayo Clinic. The survey provided background information on the
      standard of care for MM and data on maintenance. Patients were asked to estimate
      the magnitude of OS benefit that would be acceptable for various degrees of
      toxicity and cost. RESULTS: Of 1159 surveys sent, 886 patients (83.2%) responded,
      and 736 patients returned a completed survey (66% raw response rate). The most
      worrisome potential toxicity was identified as peripheral neuropathy by 27% of
      patients, cytopenias by 24%, deep vein thrombosis by 20%, fatigue by 15%, nausea
      by 8%, and diarrhea/constipation by 7%. If treatment was free, had no toxicity,
      and the OS benefit was <=1 year, then 49% of patients indicated that they would
      choose maintenance; with moderate toxicity, this proportion decreased to 42%.
      Adding a treatment cost of $25 per month decreased the proportion that would
      choose maintenance to 39% of patients. CONCLUSIONS: The current results indicated
      that willingness to receive maintenance treatment declined when actual benefits
      were provided in concrete numeric terms compared with a general statement of PFS
      benefit. The authors also observed that the magnitude of benefit required to
      consider maintenance was affected by cost and toxicity.

PMID- 24105722
TI  - Cow's milk with active immunoglobulins against Campylobacter jejuni: effects of
      temperature on immunoglobulin activity.
AB  - BACKGROUND: Adult Holstein cows were injected with an antiserum against
      Campylobacter jejuni and immunoglobulin activities in vitro were determined in
      blood and milk several weeks after injection. The immunoactivity of
      immunoglobulins in milk was measured by an ELISA after different temperature-time
      treatments (60-91 degrees C and 4-3600 s) at laboratory and pilot-plant scales.
      Kinetic and thermodynamic parameters were determined. RESULTS: An increase in
      immunoglobulin activity in milk was detected several days after injection.
      Optical densities increased by three- to seven-fold in this period. The activity
      started to decay 4-5 weeks after injection. Immunoglobulins maintained most of
      their in vitro activity under pasteurisation conditions (72 degrees C and 15 s)
      and were denatured following first-order kinetics. CONCLUSIONS: The injection
      protocol applied allows milk with specific immunoglobulins against Campylobacter
      jejuni to be obtained. Traditional pasteurisation did not reduce this activity.

PMID- 24105719
TI  - Defining the neighborhoods that escort the oocyte through its early life events
      and into a functional follicle.
AB  - The ovary functions to chaperone the most precious cargo for female individuals,
      the oocyte, thereby allowing the passage of genetic material to subsequent
      generations. Within the ovary, single oocytes are surrounded by a legion of
      granulosa cells inside each follicle. These two cell types depend upon one
      another to support follicle formation and oocyte survival. The infrastructure and
      events that work together to ultimately form these functional follicles within
      the ovary are unprecedented, given that the oocyte originates as a cell like all
      other neighboring cells within the embryo prior to gastrulation. This review
      discusses the journey of the germ cell in the context of the developing female
      mouse embryo, with a focus on specific signaling events and cell-cell
      interactions that escort the primordial germ cell as it is specified into the
      germ cell fate, migrates through the hindgut into the gonad, differentiates into
      an oocyte, and culminates upon formation of the primordial and then primary
      follicle.

PMID- 24105723
TI  - Which factors are associated with trainees' confidence in performing obstetric
      and gynecological ultrasound examinations?
AB  - OBJECTIVE: To explore the association between clinical training characteristics
      and trainees' level of confidence in performing ultrasound scans independently.
      METHODS: A cross-sectional e-survey was distributed to members of the national
      societies of junior obstetricians/gynecologists in Denmark, Sweden and Norway (n
      = 973). Multiple linear regression models were used to explore the effect that
      amount of time spent in specialized ultrasound units and clinical experience had
      on trainees' confidence in performing ultrasonography independently. Exploratory
      factor analysis was used to identify factors that contributed to trainees'
      confidence in performing ultrasonography. Trainees' ultrasound confidence was
      finally compared with their expected levels of performance. RESULTS: Of the 682
      respondents (response rate 70.1%), 621 met the inclusion criteria. Clinical
      experience and time spent in specialized ultrasound units were predictors of
      trainees' confidence in performing ultrasonography independently (P < 0.001).
      Trainees required more than 24 months of clinical experience and 12-24 days of
      training in specialized ultrasound units in order to feel confident about
      performing transvaginal and transabdominal ultrasound scans independently. Three
      factors were related to ultrasound confidence: technical aspects, image
      perception and integration of scan into patient care. There were significant
      differences between trainees' level of confidence and their expected levels of
      performance (P < 0.001). CONCLUSIONS: Clinical experience and time spent in
      specialized ultrasound units were predictors of trainees' confidence in
      performing ultrasonography independently. Discrepancies between trainees'
      confidence and their expected levels of performance raised concerns about the
      adequacy of current ultrasound training programs.

PMID- 24105724
TI  - Effect of glial cell line-derived neurotrophic factor on behavior and key members
      of the brain serotonin system in mouse strains genetically predisposed to
      behavioral disorders.
AB  - The effect of glial cell line-derived neurotrophic factor (GDNF) on behavior and
      on the serotonin (5-HT) system of a mouse strain predisposed to depressive-like
      behavior, ASC/Icg (Antidepressant Sensitive Cataleptics), in comparison with the
      parental "nondepressive" CBA/Lac mice was studied. Within 7 days after acute
      administration, GDNF (800 ng, i.c.v.) decreased cataleptic immobility but
      increased depressive-like behavioral traits in both investigated mouse strains
      and produced anxiolytic effects in ASC mice. The expression of the gene encoding
      the key enzyme for 5-HT biosynthesis in the brain, tryptophan hydroxylase-2 (Tph
      2), and 5-HT1A receptor gene in the midbrain as well as 5-HT2A receptor gene in
      the frontal cortex were increased in GDNF-treated ASC mice. At the same time,
      GDNF decreased 5-HT1A and 5-HT2A receptor gene expression in the hippocampus of
      ASC mice. GDNF failed to change Tph2, 5-HT1A , or 5-HT2A receptor mRNA levels in
      CBA mice as well as 5-HT transporter gene expression and 5-HT1A and 5-HT2A
      receptor functional activity in both investigated mouse strains. The results show
      1) a GDNF-induced increase in the expression of key genes of the brain 5-HT
      system, Tph2, 5-HT1A , and 5-HT2A receptors, and 2) significant genotype
      dependent differences in the 5-HT system response to GDNF treatment. The data
      suggest that genetically defined cross-talk between neurotrophic factors and the
      brain 5-HT system underlies the variability in behavioral response to GDNF.

PMID- 24105725
TI  - Ethanol induced the formation of beta-sheet and amyloid-like fibrils by
      surfactant-like peptide A6K.
AB  - Self-assembly of natural or designed peptides into fibrillar structures based on
      beta-sheet conformation is a ubiquitous and important phenomenon. Recently,
      organic solvents have been reported to play inductive roles in the process of
      conformational change and fibrillization of some proteins and peptides. In this
      study, we report the change of secondary structure and self-assembling behavior
      of the surfactant-like peptide A6K at different ethanol concentrations in water.
      Circular dichroism indicated that ethanol could induce a gradual conformational
      change of A6K from unordered secondary structure to beta-sheet depending upon the
      ethanol concentration. Dynamic light scattering and atomic force microscopy
      revealed that with an increase of ethanol concentration the nanostructure formed
      by A6K was transformed from nanosphere/string-of-beads to long and smooth
      fibrils. Furthermore, Congo red staining/binding and thioflavin-T binding
      experiments showed that with increased ethanol concentration, the fibrils formed
      by A6K exhibited stronger amyloid fibril features. These results reveal the
      ability of ethanol to promote beta-sheet conformation and fibrillization of the
      surfactant-like peptide, a fact that may be useful for both designing self
      assembling peptide nanomaterials and clarifying the molecular mechanism behind
      the formation of amyloid fibrils.

PMID- 24105726
TI  - Cloning and sequence analysis of neuropeptide F from the oriental tobacco budworm
      Helicoverpa assulta (Guenee).
AB  - Neuropeptide F (NPF), the invertebrate homolog of neuropeptide Y (NPY) in
      vertebrates, shares similarity of structure and function with NPY. However, a few
      NPYs were also found in some insect species. In this paper, two neuropeptide
      genes encoding a NPF and a NPY were cloned from a tobacco budworm Helicoverpa
      assulta cDNA library. The npf1 gene further produces two splicing variants of
      rnRNAs, i.e. npf1a (lacks the 120 bp segment) and npf1b (includes a 120 bp
      segment). These two splicing variants form two mature peptides, NPF1a and NPF1b
      by modification of transcripts. NPF and NPY co-exist in H. assulta. 

PMID- 24105727
TI  - p16INK4A immunohistochemical staining and predictive value for progression of
      cervical intraepithelial neoplasia grade 1: a prospective study in China.
AB  - p16(INK4A) is strongly expressed in tissues diagnosed as cervical intraepithelial
      neoplasia (CIN) and cancer in women infected with human papillomavirus (HPV), but
      few prospective studies have evaluated p16(INK4A) as a marker for the risk of low
      grade CIN (CIN1) progression. We investigated the prevalence of p16(INK4A)
      immunostaining by CIN grade and whether overexpression of p16(INK4A) in CIN1
      predicts future risk for high-grade CIN in Chinese women. 6,557 Chinese women
      aged 30-49 years were screened from 2003 to 2005 using cytology and carcinogenic
      HPV test. Colposcopy was performed on women with any abnormal result. p16(INK4A)
      Immunostaining was performed on biopsies from all women with CIN1, as well as
      randomly selected women with normal or CIN grade 2 and worse (CIN2+) biopsies.
      Women with CIN1 were followed up without treatment. Colposcopy was performed on
      all untreated women at a 2-year interval. The prevalence of p16(INK4A) staining
      was 2.7%, 42.7%, 75.5%, 79.6% and 100% among women with normal, CIN1, 2, 3 and
      cancer biopsies, respectively (p < 0.001). HPV positivity was strongly associated
      with p16(INK4A) staining [odds ratios (OR) = 12.8; 95% confidence intervals (CI):
      5.2-31.6]. p16(INK4A) staining of CIN1 biopsies at baseline was associated with
      an increased risk of finding high-grade CIN over 2 years of follow-up (OR = 1.43;
      95% CI: 0.52-3.91). The two-year cumulative incidence of CIN2+ for p16(INK4A)
      positive women was higher at 10.71% than for p16(INK4A) negative women at 1.30%
      (crude RR = 8.25, 95% CI: 1.02-66.62). p16(INK4A) overexpression is strongly
      associated with grade of CIN and risk of progression to high-grade CIN in women
      with low-grade lesions. 

PMID- 24105728
TI  - An evaluation of the role of NKG2C+ natural killer cells in protection from
      cytomegalovirus DNAemia early following allogeneic stem cell transplantation.
AB  - The role of natural killer (NK) cells in affording protection against human
      cytomegalovirus (CMV) in allogeneic stem cell transplant recipients is largely
      unknown. The current study was aimed at determining whether NKG2C+ NK cells
      confer protection from CMV DNAemia early following transplantation in patients
      lacking mono and polyfunctional CMV pp65 and IE-1-specific CD4+ and CD8+ T-cell
      responses, as measured by flow cytometry for intracellular cytokine staining.
      Fourteen out of the 36 patients included in this study developed CMV DNAemia
      between days +30 and +60 after transplant. Three patients did so after day +60.
      Peripheral blood levels of CD56(bright) CD16(-/low) and CD56(dim) CD16+ NKG2C+ NK
      cells measured at day +30 and at day +60 in patients who had or had not
      subsequent CMV DNAemia did not differ significantly. In addition, no significant
      correlation was found between CD56(bright) CD16(-/low) (sigma = -0.229; P = 0.39)
      and CD56(dim) CD16+ (sigma = -0.285; P = 0.28) NKG2C+ NK-cell levels and initial
      plasma CMV DNA loads. In summary, the data presented do not support a direct
      implication of NKG2C+ NK cells in preventing the development of CMV DNAemia or
      modulating the magnitude of CMV replication at early stages during episodes of
      CMV DNAemia in allogeneic stem cell transplant patients with unreconstituted CMV
      specific T-cell responses.

PMID- 24105730
TI  - Which inferior turbinate reduction technique best decreases nasal obstruction?

PMID- 24105729
TI  - Solid dispersion prepared by continuous cogrinding in an air jet mill.
AB  - Embedding a poorly water-soluble drug as a solid dispersion in a hydrophilic
      carrier by cogrinding is a possible strategy for enhancing the drug dissolution
      rate. Although general interest in continuous processes for manufacturing drug
      formulations has increased, many publications still focus on batch processes. The
      jet mill used in this study is a promising tool for continuous cogrinding.
      Investigation of different drug-to-carrier ratios (griseofulvin/mannitol)
      demonstrated that a drug load of 10% is best suited to investigate the enhanced
      dissolution behavior. To gain deeper insight into the underlying mechanisms, the
      coground dispersion is compared with different physical mixtures in terms of
      physicochemical properties and dissolution behavior. Differential scanning
      calorimetry and X-ray powder diffraction were used to verify the crystalline
      structure of the coground formulation. On the basis of the Hixson-Crowell model,
      particle size reduction was ruled out as the main reason for dissolution
      enhancement. An increase of surface free energies because of grinding is shown
      with contact angle measurements. Confocal Raman microscopy investigations
      revealed the drug's bulk dispersity in the coground formulation as an additional
      factor for the increased dissolution rate. In conclusion, the continuous
      cogrinding approach is a promising technique to prepare the drug in a rapidly
      dissolving, yet crystalline, form.

PMID- 24105731
TI  - Factors influencing adherence in long-term use of statins.
AB  - PURPOSE: To assess the factors influencing adherence in long-term medication use
      as exemplified by statins. METHODS: Data from an in-depth survey of Australians
      aged 45 years and over were linked to national prescription reimbursement data to
      assess medication possession ratio (MPR) for statins for the middle two years of
      a four-year period of statin possession. Poisson regression was used to calculate
      the relative risk (RR) for adherence (MPR >= 80%) for patient characteristics and
      factors related to access to and need for health care services. Separate models
      were fit for patients receiving healthcare concession subsidies and those who do
      not ('general beneficiaries'). RESULTS: In the analysis, 42 492 concessional and
      16 110 general beneficiary patients were included, with 80.1% and 56.7% showing
      MPR >= 80%, respectively. In both models, RR for adherence was significantly
      elevated for older (age 65+) and less healthy (worse self-rated health, pre
      existing heart condition or obese) individuals, and for those who had private
      health insurance. Significantly lower RR (i.e. more non-adherence) was found for
      individuals reporting speaking a language other than English at home, who were
      smokers, were employed, and had higher levels of education, and for those who
      reported psychological distress. Income had no significant relationship with
      adherence, and the pattern of adherence by remoteness of area of residence was
      inconsistent. CONCLUSIONS: Poor adherence in long-term use of statins is
      commonplace, but a number of key predictors-including age, language other than
      English spoken at home, smoking status and psychological distress-are readily
      assessable by the prescribing practice.

PMID- 24105732
TI  - Fe-catalyzed one-pot oxidative cleavage of unsaturated fatty acids into aldehydes
      with hydrogen peroxide and sodium periodate.
AB  - A one-pot method has been developed for the oxidative cleavage of internal
      alkenes into aldehydes by using 0.5 mol% of the nonheme iron complex
      [Fe(OTf)2(mix-bpbp)] (bpbp=N,N'-bis(2-picolyl)-2,2'-bipyrrolidine) as catalyst
      and 1.5 equivalents of hydrogen peroxide and 1 equivalent of sodium periodate as
      oxidants. A mixture of diastereomers of the chiral bpbp ligand can be used,
      thereby omitting the need for resolution of its optically active components. The
      cleavage reaction can be performed in one pot within 20 h and under ambient
      conditions. Addition of water after the epoxidation, acidification and subsequent
      pH neutralization are crucial to perform the epoxidation, hydrolysis, and
      subsequent diol cleavage in one pot. High aldehyde yields can be obtained for the
      cleavage of internal aliphatic double bonds with cis and trans configuration (86
      98%) and unsaturated fatty acids and esters (69-96%). Good aldehyde yields are
      obtained in reactions of trisubstituted and terminal alkenes (62-63%). The
      products can be easily isolated by a simple extraction step with an organic
      solvent. The presented protocol involves a lower catalyst loading than
      conventional methods based on Ru or Os. Also, hydrogen peroxide can be used as
      the oxidant in this case, which is often disproportionated by second- and third
      row metals. By using only mild oxidants, overoxidation of the aldehyde to the
      carboxylic acid is prevented.

PMID- 24105733
TI  - Synthesis of chemically bonded graphene/carbon nanotube composites and their
      application in large volumetric capacitance supercapacitors.
AB  - Chemically bonded graphene/carbon nanotube composites as flexible supercapacitor
      electrode materials are synthesized by amide bonding. Carbon nanotubes attached
      along the edges and onto the surface of graphene act as spacers to increase the
      electrolyte-accessible surface area. Our lamellar structure electrodes
      demonstrate the largest volumetric capacitance (165 F cm(-3) ) ever shown by
      carbon-based electrodes. 

PMID- 24105734
TI  - The sonopartogram: a novel method for recording progress of labor by ultrasound.
AB  - OBJECTIVES: Progress of labor has hitherto been assessed by digital vaginal
      examination (VE). We introduce the concept of a non-intrusive ultrasound (US)
      based assessment of labor progress (the 'sonopartogram') and investigate its
      feasibility for assessing cervical dilatation and fetal head descent and
      rotation. METHODS: This was a prospective study performed in 20 women in the
      first stage of labor in two European maternity units. Almost simultaneous
      assessment of cervical dilatation and fetal head descent and rotation were made
      by US and digital VE. RESULTS: The total number of paired US and digital VE
      assessments was 52, with a median of three per woman. Overall, 5% of
      sonopartogram parameters were not obtained compared with 18% of conventional
      digital VE parameters (P < 0.001). Assessment of cervical dilatation was possible
      in 86.5% of US examinations and 100% of digital VEs (P = 0.02), and dilatation
      was assessed as being greater by digital VE than by US (mean difference, 1.16
      (95% limits of agreement, -0.76, 3.08) cm, r(2) = 0.68, P = 0.01). Fetal head
      descent was measured in all 52 cases by both methods (r(2) = 0.33, P < 0.001),
      but correlation between the two was only moderate. Head rotation was obtainable
      in 98% of US examinations and 46% of digital VEs (P < 0.001), with a mean
      difference of -3.9 degrees  (95% limits of agreement, -144.1 degrees , 136.3
      degrees ). CONCLUSION: In this proof-of-concept study, the acquisition of data
      regarding progress of labor was more successful for the sonopartogram than the
      conventional partogram. The agreement between digital VE and US was good for
      cervical dilatation and head rotation but less so for head descent. US assessment
      of the progress of labor is feasible in most cases.

PMID- 24105735
TI  - O-xylosylation in a recombinant protein is directed at a common motif on glycine
      serine linkers.
AB  - Glycine-serine (GS) linkers are commonly used in recombinant proteins to connect
      domains. Here, we report the posttranslational O-glycosylation of a GS linker in
      a novel fusion protein. The structure of the O-glycan moiety is a xylose-based
      core substituted with hexose and sulfated hexauronic acid residues. The total
      level of O-xylosylation was approximately 30% in the material expressed in HEK
      293 cell lines. There was an approximate 10-fold reduction in O-xylosylation
      levels when the material was expressed in Chinese hamster ovary cell lines.
      Similar O-glycan structures have been reported for human urinary thrombomodulin
      and represent the initial building block for proteoglycans such as chondroitin
      sulfate and heparin. The sites of attachment, determined by electron transfer
      dissociation mass spectrometry, were localized to serine in the linker regions of
      the recombinant fusion protein. This attachment could be attributed, in part, to
      the inherent xylosyltransferase motif present in GS linkers. Elimination of the O
      glycan moiety was achieved with modified linkers containing only glycine
      residues. The aggregation and fragmentation behavior of the GGG construct were
      comparable to the GSG-linked material during thermal stress. The O-xylosylation
      reported has implications for the manufacturing consistency of recombinant
      proteins containing GS linkers.

PMID- 24105736
TI  - N-{[2-(4-Phenyl-piperazin-1-yl)-ethyl]-phenyl}-arylamides with dopamine D2 and 5
      Hydroxytryptamine 5HT(1A) activity: synthesis, testing, and molecular modeling.
AB  - The ratio of affinities toward the dopamine D2 and the 5-hydroxytryptamine 5
      HT(1A) receptors is one of the important parameters that determine the efficiency
      of antipsychotic drugs. Here, we present the synthesis of ortho-, meta-, and para
      N-{[2-(4-phenyl-piperazin-1-yl)-ethyl]-phenyl}-arylamides and their structure
      activity relationship studies on dopamine D2 and 5-hydroxytryptamine 5-HT(1A)
      receptors. It was shown that the biological activity of the described ligands
      strongly depends on their topology as well as on the nature of the heteroaryl
      group in the head of the molecules. Docking simulations together with
      conformational analysis revealed a rational explanation for the ligands'
      behavior. The molecular model of receptor-ligand interactions described herein
      provided us with a tool for the rational design of new compounds with a favorable
      D2/5-HT(1A) profile.

PMID- 24105737
TI  - Epigenetic reprogramming reverses the malignant epigenotype of the MMP/TIMP axis
      genes in tumor cells.
AB  - Cancer progression is characterized by extensive tumor invasion into the
      surrounding extracellular matrix (ECM) and migration to metastatic sites. The
      increased proteolytic degradation of the ECM during tumor invasion is directly
      dependent on the activity of matrix metalloproteinases (MMPs), counter-balanced
      by tissue inhibitors of matrix metalloproteinases (TIMPs). In this study, we
      found that unbalanced expression of MMP/TIMP axis genes in tumors was correlated
      with aberrant epigenotypes in the various gene promoters. The malignant
      epigenotypes could be therapeutically corrected by a simple defined factor
      mediated reprogramming approach. Correction of the abnormal epigenotypes by
      nuclear remodeling leads to a rebalance in the gene expression profile, an
      alteration in tumor cell morphology, attenuation of tumor cell migration and
      invasion in vitro, and reduced tumorigenicity in nude mice. We further identified
      the downregulation of the MKK-p38 MAPK signal pathway as an important underlying
      mechanism for reduced tumorigenicity in this epigenetic reprogramming model.
      These data demonstrate that the malignant phenotypes seen in cancer can be
      corrected by a nuclear remodeling mechanism, thus highlighting a novel non
      chemotherapeutic, non-radiotherapeutic approach for the treatment of cancer. 

PMID- 24105738
TI  - A novel peptide specifically targeting ovarian cancer identified by in vivo phage
      display.
AB  - Discovery of peptide ligands that can target human ovarian cancer and deliver
      chemotherapeutics offers new opportunity for cancer therapy. The advent of phage
      displayed peptide library facilitated the screening of such peptides. In vivo
      screening that set in a microanatomic and functional context was applied in our
      study, and a novel peptide WSGPGVWGASVK targeting ovarian cancer was isolated.
      The phage clone PC3-1 displaying peptide WSGPGVWGASVK can gain effective access
      to accumulate in the tumor sites after intravenous injection while reducing its
      accumulation in normal organs. Positive immunostaining of PC3-1 was located in
      both sites of tumor cells and tumor blood vessels, which resulted in a diffuse
      binding pattern through the tumor. In vitro study results confirmed the
      capability of peptide WSGPGVWGASVK binding to and being internalized by both
      tumor cells and angiogenic endothelial cells. Flow cytometry analysis revealed
      that the peptide bound to SKOV3 cells with Kd value of 5.43 +/- 0.4 MUM. Taken
      together, it suggested that peptide WSGPGVWGASVK is a lead candidate for
      delivering therapeutics to penetrate into tumors.

PMID- 24105739
TI  - Assessing adenoid hypertrophy in children: X-ray or nasal endoscopy?

PMID- 24105740
TI  - A 3 T sodium and proton composite array breast coil.
AB  - PURPOSE: The objective of this study was to determine whether a sodium phased
      array would improve sodium breast MRI at 3 T. The secondary objective was to
      create acceptable proton images with the sodium phased array in place. METHODS: A
      novel composite array for combined proton/sodium 3 T breast MRI is compared with
      a coil with a single proton and sodium channel. The composite array consists of a
      7-channel sodium receive array, a larger sodium transmit coil, and a 4-channel
      proton transceive array. The new composite array design utilizes smaller sodium
      receive loops than typically used in sodium imaging, uses novel decoupling
      methods between the receive loops and transmit loops, and uses a novel
      multichannel proton transceive coil. The proton transceive coil reduces coupling
      between proton and sodium elements by intersecting the constituent loops to
      reduce their mutual inductance. The coil used for comparison consists of a
      concentric sodium and proton loop with passive decoupling traps. RESULTS: The
      composite array coil demonstrates a 2-5* improvement in signal-to-noise ratio for
      sodium imaging and similar signal-to-noise ratio for proton imaging when compared
      with a simple single-loop dual resonant design. CONCLUSION: The improved signal
      to-noise ratio of the composite array gives breast sodium images of unprecedented
      quality in reasonable scan times.

PMID- 24105742
TI  - Experimental and computational studies of anti-Bredt amidinium salts.
AB  - Experimental and computational investigations of anti-Bredt amidinium salts are
      presented. Calculations show that the pyramidalization of an amino group can
      significantly destabilize the formal carbocation center of amidiniums, due to the
      decreased pi donation. In some cases, the unfavorable -I effect of nitrogen
      surpasses its beneficial +M effect, and amidiniums become less stable than
      iminiums. It is shown that although 1-aza-3-azonia[3.3.1]bicyclo-non-2-enes can
      be isolated, they feature a nonclassical reactivity, which is more typical for
      iminium than amidinium salts, such as pronounced electrophilicity and
      azomethineylide instead of carbene formation. 

PMID- 24105741
TI  - Detection and molecular characterization of diarrhea causing viruses in single
      and mixed infections in children: a comparative study between Bangladesh and
      Turkey.
AB  - The incidence and mortality caused by diarrhea differ among countries. The
      prevalence of different enteric viruses, their molecular characteristics, and
      infections with multiple viruses might affect the disease incidence and mortality
      caused by diarrhea. The objective of this study was to determine the distribution
      and molecular characteristics of enteric viruses in children with diarrhea in
      Turkey and Bangladesh. A total of 288 stool samples that were negative for group
      A rotavirus were collected from children aged <5 years with acute diarrhea who
      presented to hospitals in Turkey and Bangladesh. The samples were screened for
      human bocavirus (HBoV), astrovirus (HAstV), norovirus (NoV), and adenovirus
      (AdV). Phylogenetic analyses of the targeted virus genes were performed. In
      Turkey, viruses were detected in 87/150 samples (58%), which included 69 (79.3%)
      with single viruses and 18 (20.7%) with multiple viruses. AdV was the most common
      virus, followed by HBoV. In Bangladesh, viruses were detected in 123/138 samples
      (89.1%), which included 29 (23.6%) with single viruses and 94 (76.4%) with
      multiple viruses. NoV GII was the most common, followed by AdV. The dominant
      genotypes among the virus species were HBoV 2A, HAstV 1, NoV GI type 1, and AdV
      40. For NoV GII, the Hunter variant of genotype 4 in Turkey and genotype 17 in
      Bangladesh were the most common among the sequenced strains. It was concluded
      that the distribution of the viruses associated with diarrhea in Turkish and
      Bangladeshi children was different. Enteric viruses and mixed infections were
      more prevalent in Bangladesh than in Turkey.

PMID- 24105743
TI  - Oncogenic RAS directs silencing of tumor suppressor genes through ordered
      recruitment of transcriptional repressors.
AB  - We previously identified 28 cofactors through which a RAS oncoprotein directs
      transcriptional silencing of Fas and other tumor suppressor genes (TSGs). Here we
      performed RNAi-based epistasis experiments and found that RAS-directed silencing
      occurs through a highly ordered pathway that is initiated by binding of ZFP354B,
      a sequence-specific DNA-binding protein, and culminates in recruitment of the DNA
      methyltransferase DNMT1. RNAi and pharmacological inhibition experiments reveal
      that silencing requires continuous function of RAS and its cofactors and can be
      rapidly reversed, which may have therapeutic implications for reactivation of
      silenced TSGs in RAS-positive cancers. 

PMID- 24105744
TI  - A SUMO-dependent interaction between Senataxin and the exosome, disrupted in the
      neurodegenerative disease AOA2, targets the exosome to sites of transcription
      induced DNA damage.
AB  - Senataxin (SETX) is an RNA/DNA helicase implicated in transcription termination
      and the DNA damage response and is mutated in two distinct neurological
      disorders: AOA2 (ataxia oculomotor apraxia 2) and ALS4 (amyotrophic lateral
      sclerosis 4). Here we provide evidence that Rrp45, a subunit of the exosome,
      associates with SETX in a manner dependent on SETX sumoylation. We show that the
      interaction and SETX sumoylation are disrupted by SETX mutations associated with
      AOA2 but not ALS4. Furthermore, Rrp45 colocalizes with SETX in distinct foci upon
      induction of transcription-related DNA damage. Our results thus provide evidence
      for a SUMO-dependent interaction between SETX and the exosome, disrupted in AOA2,
      that targets the exosome to sites of DNA damage. 

PMID- 24105746
TI  - Global harmonization of food safety regulations: perspectives from Japan after
      the Fukushima nuclear accident.
AB  - Japanese food self-sufficiency was only 39% on the basis of kcal in 2012, so
      Japan relies heavily on imported food. Hence the necessity of having
      international rules on the regulation of food contaminants is important
      especially for countries like Japan that depend on food imports. A One-Stop
      Testing system is desired, in which the test result obtained from a single
      testing laboratory is accepted as valid worldwide. To establish this system,
      laboratory accreditation under international standards is a necessary step.
      Furthermore, the importance of supply of reference materials for internal quality
      control and proficiency testing for external quality control of each laboratory's
      analytical system is reviewed in connection with the experience of radioactive
      nuclide contamination resulting from the Fukushima nuclear power plant accident
      in March 2011.

PMID- 24105745
TI  - The effect of intra-uterine growth restriction on blood lipids and response to
      exercise training.
AB  - OBJECTIVES: To determine if a small body size at birth is associated with an
      unfavorable metabolic profile and a reduced response to exercise training in
      young adults. METHODS: Thirty-six college students, all singletons born to term,
      participated. Subjects were defined as either high ponderal index (HIGHPI) or low
      ponderal index (LOWPI). LOWPI was defined as below the 10th percentile of the PI
      for-gestational age distribution. HIGHPI was defined as greater than the 10th
      percentile. Subject groups were matched pair-wise on age, sex, BMI, and
      pretraining physical activity level. Subjects completed an 8-week aerobic
      exercise program. Pre- and post-training measurements included a blood lipid
      profile. RESULTS: The LOWPI group, when compared to the HIGHPI group, exhibited
      higher total (183.6 mg dl(-1) vs. 150.9, P = 0.04) and LDL cholesterol (114.8 mg
      dl(-1) vs. 80.2, P = 0.019) values prior to exercise training. After training,
      these values decreased in the LOWPI group, eliminating the group difference.
      Various blood lipid ratios were more favorable for the HIGHPI group, both before
      and after training. The inclusion of maternal smoking as a covariate attenuated
      group differences for pretraining TChol, pre-training TG:HDL, and post-training
      HDL cholesterol. CONCLUSIONS: An 8-week exercise program corrected some, but not
      all, of the differences in blood lipid values between the LOWPI and HIGHPI group.
      The persistent group difference in blood lipid ratios suggests a higher long-term
      risk of chronic disease in the LOWPI group independent of lifestyle intervention.

PMID- 24105747
TI  - Ranking relative hydrogen-bond strengths in hydroxybenzoic acids for crystal
      engineering purposes.
AB  - Systematic co-crystallizations resulting in a total of six new crystal structures
      involving either 3-hydroxy- or 4-hydroxybenzoic acid, complemented by calculated
      molecular electrostatic potential surfaces and existing structural data, have
      shown that in a competitive molecular recognition situation, the -OH moiety is a
      more effective hydrogen-bond donor than the -COOH moiety which, in turn,
      highlights that electrostatic charge can offer more useful guidance than acidity
      for predicting competitive hydrogen-bond preferences.

PMID- 24105748
TI  - Highly stretchable nanoparticle helices through geometric asymmetry and surface
      forces.
AB  - Geometric asymmetry and surface forces are used directly the shape transformation
      of two-dimensional nanoparticle (NP)-based ribbons into three-dimensional
      helices. The balance between elasticity and surface tension dictates the helical
      radius dimension. NP helical ribbons have exceptional mechanical properties,
      displaying high stretchability, helical shape recovery after extension, and low
      strain stiffness values similar to biological helices. 

PMID- 24105749
TI  - What lies within: novel strategies in immunotherapy for non-small cell lung
      cancer.
AB  - Immunotherapy has become an increasingly important therapeutic strategy for those
      with cancer, with phase III studies demonstrating survival advantages in melanoma
      and castration-resistant prostate cancer. Non-small cell lung cancer (NSCLC) is a
      promising target for the next generation of immune-based strategies. In this
      article, we examine the current state of the art in lung cancer immunotherapy,
      including vaccines that specifically target lung tumor antigens and immune
      checkpoint antibodies such as antiprogrammed death 1 (anti-PD-1). Both approaches
      harness innate immunity against tumors by suppressing tumor-induced immune
      paresis. Methods. To identify relevant clinical trials of immunotherapy in NSCLC,
      PubMed and Medline databases were searched using the terms "immunotherapy" and
      "NSCLC," and several other therapy-specific search terms (e.g., PD-1, NSCLC).
      Additionally, abstracts presented at international lung cancer symposia, the
      American Society of Clinical Oncology annual meeting, and the European Society of
      Medical Oncology annual meeting between 2005 and 2013 were evaluated. Results.
      Large international phase III trials of NSCLC vaccines have completed accrual in
      both the adjuvant and metastatic disease settings. Results of the START study
      were disappointing, but results from other studies are still awaited. Immune
      checkpoint modulation has shown promise, with separate phase I studies of the
      anti-PD-1 antibody, nivolumab, and anti-PD-L1 antibody, MPDL3280A, demonstrating
      good tolerance and durable responses for certain patients with NSCLC who were
      heavily pretreated. Conclusions. Immune-based strategies have shown initial
      promise for early- and advanced-stage NSCLC. Validating these findings in
      randomized studies and discovering durable biomarkers of response represent the
      next challenges for investigation. 

PMID- 24105750
TI  - A randomized study of interferon alpha-2b versus no treatment as consolidation
      after high dose therapy and autologous stem cell transplantation for patients
      with relapsed lymphoma.
AB  - Patients with lymphoma who have experienced a first relapse or progression and
      have disease deemed sensitive to salvage chemotherapy nevertheless have a high
      likelihood of having a second relapse. To decrease the likelihood of a second
      relapse after high-dose therapy (HDT) and autologous stem cell transplantation
      (ASCT), interferon (IFN) alpha-2b was given in a prospective randomized
      international trial. Methods. In this trial, 221 patients with varying histologic
      diagnoses (8 small lymphocytic, 37 follicular, 9 mantle, 90 diffuse large B-cell,
      20 peripheral T-cell, 3 high-grade B-cell non-Hodgkin lymphoma, and 54 Hodgkin
      lymphoma) were randomly assigned to receive no further treatment (arm A: 117
      patients) or IFNalpha-2b, 3 MU three times weekly, for 18 months (arm B: 104
      patients). Results. In arm B, 21 patients (20%) did not receive IFNalpha-2b
      because of early progression or absence of hematologic recovery, 29 patients
      (28%) completed the 18 months of treatment, and 54 patients (52%) interrupted
      treatment because of progression (23%) or toxicity (29%). Event-free survival and
      overall survival were not different between the two arms on an intent-to-treat
      analysis and also if analysis was restricted to patients who were alive and had
      not experienced disease progression three months after transplantation. The study
      was not sufficiently powered to evaluate effects in histologic subtypes.
      Conclusion. In this trial, post-autograft IFNalpha-2b did not improve outcomes in
      a heterogeneous group of patients with lymphoma. 

PMID- 24105751
TI  - A double-blind, randomized phase II study to evaluate the safety and efficacy of
      acetyl-L-carnitine in the prevention of sagopilone-induced peripheral neuropathy.
AB  - Peripheral neuropathy (PN) is a recognized side effect of microtubule-targeting
      agents and the most clinically relevant toxicity observed with the epothilone
      sagopilone (SAG). Studies suggest that acetyl-L-carnitine (ALC) may prevent
      chemotherapy-induced PN. We conducted a prospective, placebo (PBO)-controlled,
      double-blind, randomized trial to investigate the safety and efficacy of ALC for
      the prevention of SAG-induced PN. Methods. Patients with ovarian cancer (OC) or
      castration-resistant prostate cancer (CRPC) and no evidence of neuropathy
      received SAG (16 mg/m(2) intravenously over 3 hours every 3 weeks) with ALC
      (1,000 mg every 3 days) or placebo (PBO). The primary endpoint was incidence of
      PN within six or fewer cycles in both treatment groups. Results. Overall, 150
      patients enrolled (98 OC patients, 52 CRPC patients), with 75 per treatment arm.
      No significant difference in overall PN incidence was observed between treatment
      arms. The incidence of grade >=3 PN was significantly lower in the ALC arm in OC
      patients. Median duration of neuropathy was similar between treatment arms. The
      best overall response (according to the modified Response Evaluation Criteria in
      Solid Tumors), response according to tumor markers, time-to-event variables, and
      discontinuations because of adverse events (AEs) were comparable between
      treatment arms. Conclusion. Administration of ALC with SAG did not result in a
      significant difference in overall PN incidence compared with a PBO. OC patients
      in the SAG/ALC arm had a significantly lower incidence of grade 3 or 4 PN
      compared with OC patients in the SAG/PBO arm. 

PMID- 24105752
TI  - No evidence for mutations in NLRP7 and KHDC3L in women with androgenetic
      hydatidiform moles.
AB  - OBJECTIVE: The objective of this study was to evaluate the mutational spectrum of
      NLRP7 and KHDC3L (C6orf221) in women with sporadic and recurrent androgenetic
      complete hydatidiform moles (AnCHM) and biparental hydatidiform moles (BiHM) to
      address the hypothesis that autosomal recessive mutations in these genes are only
      or primarily associated with BiHM. METHOD: We recruited 16 women with suspected
      recurrent and sporadic AnCHM and five women with suspected BiHM in addition to
      their reproductive partners into our study. We then sequenced the coding exons of
      NLRP7 and KHDC3L from DNA isolated from either blood or saliva from the study
      subjects. RESULTS: Sequence analysis of NLRP7 and KHDC3L revealed previously
      described single nucleotide polymorphisms in patients with AnCHM. However, in
      patients with BiHM, we identified a novel homozygous mutation and a previously
      described intragenic duplication of exons 2 to 5 in NLRP7, both of which are
      likely to be disease causing. We did not identify mutations in KHDC3L in patients
      with either form of hydatidiform moles. CONCLUSIONS: The absence of mutations in
      women with AnCHM supports a role for NLRP7 or KHDC3L in BiHM only. The absence of
      mutations in KHDC3L in women with BiHM is consistent with its minor role in this
      disease compared with NLRP7, the major BiHM gene.

PMID- 24105753
TI  - Titanocene(III)-catalyzed 6-exo versus 7-endo cyclizations of epoxypolyprenes:
      efficient control and synthesis of versatile terpenic building blocks.
AB  - In this article, a complete study on the selectivity of titanocene(III)
      cyclization of epoxypolyprenes is presented. The requirements for the formation
      of six- or seven-membered rings during these cyclizations are determined, taking
      into account the different substitution pattern in the epoxypolyprene precursor.
      Thus, a complete selectivity to 6-exo or 7-endo cyclization process has been
      achieved, yielding mono-, bi-, and even tricyclic compounds, constituting a new
      and efficient access to this type of derivative. Additionally, this procedure
      opens the possibility to prepare excellent building blocks for the synthesis of
      polycyclic compounds with a trisubstituted oxygenated function, which is present
      in several natural terpenes. 

PMID- 24105754
TI  - Characterization of a porcine model of post-operative pain.
AB  - BACKGROUND: Management of acute pain related to surgical intervention, termed
      post-operative pain or POP, continues to be a major healthcare challenge. While
      the rat plantar incision model provides valuable data to researchers about the
      mechanisms mediating POP, the development of topical and localized treatments in
      small animal models is limited. To help address these issues, we describe here
      the characterization of a large animal model of incisional pain. METHODS: Pigs
      underwent full-skin incision or full-skin and muscle incision and retraction
      (SMIR). Withdrawal thresholds were determined using the Von Frey test at
      baseline, 0.5-12 h post-surgery and on days 1, 2, 3, 5 and 7 post-surgery. The
      analgesic effects of systemic morphine [0.1 or 1.0 mg/kg intramuscular (i.m.)
      dose] and local anaesthetic ropivacaine were studied. Spontaneous pain-like
      behaviours were scored and analysed. The effects on wound healing were evaluated
      by gross observation and by histopathological examination. RESULTS: Pigs
      incurring SMIR demonstrated significantly increased mechanical hypersensitivity
      compared with pigs that underwent full-skin incision only (p < 0.05). Maximal
      analgesia was achieved with morphine (1 mg/kg i.m. dose) at 0.5 h post-treatment.
      Local treatment with ropivacaine was effective at increasing the withdrawal
      threshold to Von Frey filaments compared with saline control (p < 0.05) for a
      period of at least 6 h. Wounds healed normally with no signs of infection,
      redness or swelling. CONCLUSIONS: We propose that the pig model of incisional
      pain can provide an appropriate translational model for validating new topical
      and localized treatments for POP in humans.

PMID- 24105755
TI  - 'He's hard work, but he's worth it'. The experience of caregivers of individuals
      with intellectual disabilities and challenging behaviour: a meta-synthesis of
      qualitative research.
AB  - BACKGROUND: The purpose of this review is to synthesize the qualitative
      literature on the perspectives of those caring for a family member with
      intellectual disabilities and challenging behaviour, with a focus on their
      experiences of support services. MATERIALS AND METHODS: A thorough literature
      search resulted in 17 studies being selected for inclusion in the meta-synthesis.
      RESULTS: Five primary themes were identified: (i) love, (ii) altered identity,
      (iii) crisis management, (iv) support is not just 'challenging behaviour'
      services, and (v) the future: low expectations, high hopes. CONCLUSIONS: Carers
      spoke of the deep love for their family member and of the chronic strain the
      demands of caregiving placed upon them. Support services often caused additional
      problems and high levels of stress for caregivers, although there were also
      reports of good practice. The findings may inform clinicians and service
      providers about how best to support families of individuals with challenging
      behaviour.

PMID- 24105756
TI  - Advances in cancer epidemiology in Japan.
AB  - Epidemiologists in Japan have been performing calculations to estimate nationwide
      cancer incidence rates as well as 5-year survival rates using population-based
      cancer registry data. There have been remarkable changes in cancer incidence
      and/or mortality in cancers of the lung, liver and stomach, which were thought to
      be attributed to the changing impact of exposure to cigarette smoking, chronic
      hepatitis C virus infection and Helicobacter pylori infection, respectively. In
      systematic reviews providing evidence in risk/protective factors for cancer sites
      using case-control and cohort studies of the Japanese population, there were
      associations between cancer sites (esophagus, stomach, colo-rectum, liver,
      pancreas, lung and breast) and various lifestyle factors. In the past 10 years, a
      hospital-based case-control study at Aichi Cancer Center provided valuable
      evidence of gene-environment interaction on the development of cancer [i.e., the
      effects of aldehyde dehydrogenase-2 (ALDH2) polymorphism and heavy alcohol
      drinking on esophageal cancer, ALDH2 polymorphism and smoking on lung cancer,
      methylenetetrahydrofolate reductase polymorphism and heavy alcohol drinking on
      pancreatic cancer]. The database with stored DNA was also used and identified
      seven loci containing significant but low-penetrance polymorphisms associated
      with the development of breast cancer. These findings together with established
      risk factors are likely to be useful to predict personalized breast cancer risk
      in East Asian women. In 2005, the Japan Multi-Institution Collaborative Cohort (J
      MICC) study was launched to elucidate gene-environment interactions as well as to
      confirm preclinical diagnostic biomarkers of cancer. J-MICC, which has recruited
      92,000 healthy individuals by the end of 2012, will follow the individuals until
      2025. 

PMID- 24105758
TI  - Management specificities of congenital laryngeal stenosis: external and
      endoscopic approaches.
AB  - OBJECTIVES/HYPOTHESIS: This study aimed to report our experience in the
      management of congenital laryngeal stenosis and to compare our series and results
      to published data in the literature. STUDY DESIGN: Retrospective case series.
      Tertiary referral center for rare pediatric head and neck malformations. METHODS:
      Medical charts of patients diagnosed with congenital laryngeal stenosis in our
      institution were reviewed over a 15-year period, from 1996 to 2011. Surgical
      treatment consisted of an endoscopic procedure, open laryngeal surgery (OLS), or
      a combination of both. RESULTS: Sixteen patients met the inclusion criteria for
      the study and were divided in two groups: the endoscopic laryngoplasty (EL)
      group, with patients who underwent the endoscopic procedure as first-line
      treatment, and the OLS group, whose patients underwent open laryngoplasty with
      cartilage graft as first-line treatment. Each group contained eight patients with
      grade II to IV congenital stenosis. All patients, except one in the EL group,
      achieved a good result (<50% residual stenosis) at the end of the follow-up.
      CONCLUSIONS: This case series suggests that EL, with incision of the subglottic
      laryngeal cartilages with cold steel instruments and balloon dilation, is a safe
      and effective treatment for congenital laryngeal stenosis grade II to IV. This
      procedure could be considered as an alternative option to OLS, even as a first
      line procedure. An endoscopic procedure does not preclude the possibility for an
      open laryngeal procedure in case of failure. A prolonged follow-up is mandatory.
      LEVEL OF EVIDENCE: 4.

PMID- 24105757
TI  - Genetic drift of influenza A(H3N2) viruses during two consecutive seasons in 2011
      2013 in Corsica, France.
AB  - The 2011-2012 and 2012-2013 post-pandemic influenza outbreaks were characterized
      by variability in the A(H3N2) influenza viruses, resulting in low to moderate
      vaccine effectiveness (VE). The aim of this study was to investigate the
      molecular evolution and vaccine strain match of the A(H3N2) influenza viruses,
      having been circulated throughout the population of the French Corsica Island in
      2011-2012 and again in 2012-2013. Clinical samples from 31 patients with
      confirmed A(H3N2) influenza viruses were collected by general practitioners (GPs)
      over these two consecutive seasons. An analysis of genetic distance and antigenic
      drift was conducted. Based on a hemagglutinin (HA) aminoacid sequence analysis,
      the Corsican A(H3N2) viruses fell into the A/Victoria/208/2009 genetic clade,
      group 3. All influenza viruses were characterized by at least four fixed amino
      acid mutations which were: N145S (epitope A); Q156H and V186G (epitope B) Y219S
      (epitope D), with respect to the A/Perth/16/2009 (reference vaccine strain for
      the 2011-2012) and the A/Victoria/361/2011 (reference vaccine strain for the 2012
      2013). Using the p(epitope) model, the percentages of the perfect match VE
      estimated against circulated strains declined within and between seasons, with
      estimations of <50%. Overall, these results seem to indicate an antigenic drift
      of the A(H3N2) influenza viruses which were circulated in Corsica. These findings
      highlight the importance of the continuous and careful surveillance of genetic
      changes in the HA domain during seasonal influenza epidemics, in order to provide
      information on newly emerging genetic variants.

PMID- 24105759
TI  - Assessing multidimensional worry in cancer survivors.

PMID- 24105760
TI  - Body fat and facial shape are correlated in female adolescents.
AB  - OBJECTIVES: Relative body weight is not only an important indicator for health
      and reproductive condition, but also subject to stereotypes and stigmatization.
      It can be reliably assessed from adult faces alone, yet the facial correlates,
      especially in adolescents, remain largely unidentified. This study was designed
      to determine the facial features of adolescent girls that change with body fat
      proportion using a modern, comprehensive technique for shape analysis. METHODS:
      Standardized frontal facial photographs of 22 Caucasian female adolescents (mean
      age 15.8 +/- 2.7 years) were taken, and body height, body weight, and body fat
      proportion measured. Seventy-two somatometric measurement points were digitized
      on each photograph and their Cartesian coordinates regressed onto body fat
      proportion. Geometric morphometrics also enabled visualizing the statistical
      results as shapes. RESULTS: Body fat proportion explained 8.7% of the facial
      shape variation (10,000 permutations, P = 0.047). Girls with high body fat had a
      relatively rounder and larger lower face, relatively smaller eyes, and a shorter
      and wider nose, fuller lips and downturned corners of the mouth. Low body fat was
      associated with a more angular lower face and a pointier chin, relatively larger
      eyes and a longer nose. The lips were wider and thinner, the corners of the mouth
      upturned. CONCLUSION: Body fat proportion is a substantial factor in facial shape
      variation of female adolescents. The potential influence of the corresponding
      facial features on social perception is discussed. Prospects for future research
      including novel possibilities for stimuli design (GM morphs) are highlighted.

PMID- 24105761
TI  - Synthesis and antiproliferative activity of quinolone nucleosides against the
      human myelogenous leukemia k-562 cell line.
AB  - A set of 6-substituted quinolone nucleosides linked to aniline or phenol via N or
      O heteroatom-bridges presenting new compounds were synthesized by palladium
      catalyzed Buchwald-Hartwig cross-coupling reactions. 6-Bromoquinolone nucleoside
      precursors, being protected by either benzoyl or TBDMS protecting groups on the
      ribose moiety, were subjected to different Buchwald-Hartwig conditions as the key
      step. Defined deprotection steps led, in good yields, to the final target
      compounds that carry, in position 3, either ester, acid, or amide functions.
      Thus, a series of novel quinolone nucleoside derivatives was obtained via a
      convergent synthesis route. Biological tests in human chronic myelogenous
      leukemia K562 cells exerted an efficient antiproliferative activity for two of
      them without induction of differentiation. These novel nucleosides deserve
      further experiments to determine their antiproliferative effects on other CML
      cell lines. 

PMID- 24105762
TI  - Lyotropic liquid crystal to soft mesocrystal transformation in hydrated salt
      surfactant mixtures.
AB  - Hydrated CaCl2, LiI, and MgCl2 salts induce self-assembly in nonionic surfactants
      (such as C12H25(OCH2CH2)10OH) to form lyotropic liquid-crystalline (LLC)
      mesophases that undergo a phase transition to a new type of soft mesocrystal
      (SMC) under ambient conditions. The SMC samples can be obtained by aging the LLC
      samples, which were prepared as thin films by spin-coating, dip-coating, or drop
      casting of a clear homogenized solution of water, salt, and surfactant over a
      substrate surface. The LLC mesophase exists up to a salt/surfactant mole ratio of
      8, 10, and 4 (corresponding to 59, 68, and 40 wt% salt/surfactant) in the CaCl2,
      LiI, and MgCl2 mesophases, respectively. The SMC phase can transform back to a
      LLC mesophase at a higher relative humidity. The phase transformations have been
      monitored using powder X-ray diffraction (PXRD), polarized optical microscopy
      (POM), and FTIR techniques. The LLC mesophases only diffract at small angles, but
      the SMCs diffract at both small and wide angles. The broad surfactant features in
      the FTIR spectra of the LLC mesophases become sharp and well resolved upon SMC
      formation. The unit cell of the mesophases expands upon SMC transformation, in
      which the expansion is largest in the MgCl2 and smallest in the CaCl2 systems.
      The POM images of the SMCs display birefringent textures with well-defined edges,
      similar to crystals. However, the surface of the crystals is highly patterned,
      like buckling patterns, which indicates that these crystals are quite soft. This
      unusual phase behavior could be beneficial in designing new soft materials in the
      fields of phase-changing materials and mesostructured materials, and it
      demonstrates the richness of the phase behavior in the salt-surfactant
      mesophases.

PMID- 24105763
TI  - 25th anniversary article: interfacing nanoparticles and biology: new strategies
      for biomedicine.
AB  - The exterior surface of nanoparticles (NPs) dictates the behavior of these
      systems with the outside world. Understanding the interactions of the NP surface
      functionality with biosystems enables the design and fabrication of effective
      platforms for therapeutics, diagnostics, and imaging agents. In this review, we
      highlight the role of chemistry in the engineering of nanomaterials, focusing on
      the fundamental role played by surface chemistry in controlling the interaction
      of NPs with proteins and cells. 

PMID- 24105764
TI  - The novel human influenza A(H7N9) virus is naturally adapted to efficient growth
      in human lung tissue.
AB  - A novel influenza A virus (IAV) of the H7N9 subtype has been isolated from
      severely diseased patients with pneumonia and acute respiratory distress syndrome
      and, apparently, from healthy poultry in March 2013 in Eastern China. We
      evaluated replication, tropism, and cytokine induction of the A/Anhui/1/2013
      (H7N9) virus isolated from a fatal human infection and two low-pathogenic avian
      H7 subtype viruses in a human lung organ culture system mimicking infection of
      the lower respiratory tract. The A(H7N9) patient isolate replicated similarly
      well as a seasonal IAV in explanted human lung tissue, whereas avian H7 subtype
      viruses propagated poorly. Interestingly, the avian H7 strains provoked a strong
      antiviral type I interferon (IFN-I) response, whereas the A(H7N9) virus induced
      only low IFN levels. Nevertheless, all viruses analyzed were detected
      predominantly in type II pneumocytes, indicating that the A(H7N9) virus does not
      differ in its cellular tropism from other avian or human influenza viruses.
      Tissue culture-based studies suggested that the low induction of the IFN-beta
      promoter correlated with an efficient suppression by the viral NS1 protein. These
      findings demonstrate that the zoonotic A(H7N9) virus is unusually well adapted to
      efficient propagation in human alveolar tissue, which most likely contributes to
      the severity of lower respiratory tract disease seen in many patients.
      IMPORTANCE: Humans are usually not infected by avian influenza A viruses (IAV),
      but this large group of viruses contributes to the emergence of human pandemic
      strains. Transmission of virulent avian IAV to humans is therefore an alarming
      event that requires assessment of the biology as well as pathogenic and pandemic
      potentials of the viruses in clinically relevant models. Here, we demonstrate
      that an early virus isolate from the recent A(H7N9) outbreak in Eastern China
      replicated as efficiently as human-adapted IAV in explanted human lung tissue,
      whereas avian H7 subtype viruses were unable to propagate. Robust replication of
      the H7N9 strain correlated with a low induction of antiviral beta interferon (IFN
      beta), and cell-based studies indicated that this is due to efficient suppression
      of the IFN response by the viral NS1 protein. Thus, explanted human lung tissue
      appears to be a useful experimental model to explore the determinants
      facilitating cross-species transmission of the H7N9 virus to humans.

PMID- 24105765
TI  - Relapse after treatment with miltefosine for visceral leishmaniasis is associated
      with increased infectivity of the infecting Leishmania donovani strain.
AB  - Leishmania donovani is an intracellular protozoan parasite that causes
      leishmaniasis, which can range from a self-healing cutaneous disease to a fatal
      visceral disease depending on the infecting species. Miltefosine is currently the
      latest and only oral antileishmanial that came out of drug discovery pipelines in
      the past few decades, but recent reports indicate a significant decline in its
      efficacy against visceral leishmaniasis (also known as kala-azar) in the Indian
      subcontinent. This relapse rate of up to 20% within 12 months after treatment was
      shown not to be related to reinfection, drug quality, drug exposure, or drug
      resistant parasites. We therefore aimed to assess other phenotypes of the
      parasite that may affect treatment outcome and found a significant association
      between the number of metacyclic parasites, parasite infectivity, and patient
      treatment outcome in the Indian subcontinent. Together with previous studies on
      resistance of L. donovani against pentavalent antimonials, these data suggest
      that the infectivity of the parasite, or related phenotypes, might be a more
      determinant factor for treatment failure in visceral leishmaniasis than drug
      susceptibility, warranting a reassessment of our current view on treatment
      failure and drug resistance in leishmaniasis and beyond. IMPORTANCE: The high
      miltefosine relapse rate poses a major challenge for the current Kala-Azar
      Elimination Program in the Indian subcontinent and other leishmaniasis control
      programs worldwide. This relapse rate could not be related to reinfection, drug
      resistant parasites, or reduced treatment quality. Here we report that an
      increased infectivity of the parasite is associated with miltefosine relapse of
      visceral leishmaniasis (VL) patients. These results supplement those obtained
      with antimonial-resistant L. donovani where an increased infectivity was also
      observed. This challenges the current view of Leishmania drug susceptibility
      being the biggest parasitic factor that contributes to treatment failure in
      leishmaniasis. These selected more infectious parasites may pose an additional
      burden to leishmaniasis control programs, highlighting the importance of
      multifaceted control measures to achieve leishmaniasis elimination in the Indian
      subcontinent and other regions where leishmaniasis is endemic.

PMID- 24105766
TI  - CodY is a global regulator of virulence-associated properties for Clostridium
      perfringens type D strain CN3718.
AB  - CodY is known to regulate various virulence properties in several Gram-positive
      bacteria but has not yet been studied in the important histotoxic and intestinal
      pathogen Clostridium perfringens. The present study prepared an isogenic codY
      null mutant in C. perfringens type D strain CN3718 by insertional mutagenesis
      using the Targetron system. Western blot analysis indicated that, relative to
      wild-type CN3718 or a complementing strain, this isogenic codY mutant produces
      reduced levels of epsilon toxin (ETX). Using supernatants from cultures of the
      wild-type, codY-null mutant, and complementing strains, CodY regulation of ETX
      production was shown to have cytotoxic consequences for MDCK cells. The CodY
      regulatory effect on ETX production was specific, since the codY-null mutant
      still made wild-type levels of alpha-toxin and perfringolysin O. Sialidase
      activity measurements and sialidase Western blot analysis of supernatants from
      CN3718 and its isogenic derivatives showed that CodY represses overall
      exosialidase activity due to a reduced presence of NanH in culture supernatants.
      Inactivation of the codY gene significantly decreased the adherence of CN3718
      vegetative cells or spores to host Caco-2 cells. Finally, the codY mutant showed
      increased spore formation under vegetative growth conditions, although
      germination of these spores was impaired. Overall, these results identify CodY as
      a global regulator of many C. perfringens virulence-associated properties.
      Furthermore, they establish that, via CodY, CN3718 coordinately regulates many
      virulence-associated properties likely needed for intestinal infection.
      IMPORTANCE: Clostridium perfringens is a major human and livestock pathogen
      because it produces many potent toxins. C. perfringens type D strains cause
      intestinal infections by producing toxins, especially epsilon toxin (ETX).
      Previous studies identified CodY as a regulator of certain virulence properties
      in other Gram-positive bacteria. Our study now demonstrates that CodY is a global
      regulator of virulence-associated properties for type D strain CN3718. It
      promotes production of ETX, attachment of CN3718 vegetative cells or spores to
      host enterocyte-like Caco-2 cells, and spore germination; the last two effects
      may assist intestinal colonization. In contrast, CodY represses sporulation.
      These results provide the first evidence that CodY can function as a global
      regulator of C. perfringens virulence-associated properties and that this strain
      coordinately regulates its virulence-associated properties using CodY to increase
      ETX production, host cell attachment, and spore germination but to repress
      sporulation, as would be optimal during type D intestinal infection.

PMID- 24105767
TI  - Potassium uptake systems in Staphylococcus aureus: new stories about ancient
      systems.
AB  - Staphylococcus aureus is a hardy organism that can survive high-salt conditions
      better than many other bacteria. This characteristic is thought to help S. aureus
      survive in the nares and on the skin of the human host and is used to selectively
      propagate and identify Staphylococcus species. However, the mechanism that allows
      S. aureus to tolerate such high-salt conditions is not well understood. A recent
      study in mBio by A. Price-Whelan et al. [mBio 4(4):e00407-13, 2013,
      doi:10.1128/mBio.00407-13] highlights the importance of potassium uptake in this
      process. This commentary provides a perspective of the study by Price-Whelan et
      al. as well as other recently reported work on potassium uptake and transport
      systems in S. aureus.

PMID- 24105768
TI  - Effect of molecular weight profile of sorghum proanthocyanidins on resistant
      starch formation.
AB  - BACKGROUND: There is a growing interest to increase resistant starch (RS) in
      foods through natural modification of starch. Sorghum tannins (proanthocyanidins,
      PAs) were recently reported to interact with starch, increasing RS. However,
      there is no information about how the molecular weight profile of PAs affects RS
      formation. This study investigated how different-molecular-weight PAs from
      sorghum affected RS formation in different starch models. RESULTS: The levels of
      RS were higher (331-437 mg g(-1)) when high-amylose starch was cooked with
      phenolic extracts containing mostly high-molecular-weight PAs compared with
      extracts containing lower-molecular-weight PAs or monomeric catechin (249-285 mg
      g(-1)). In general, binding capacity of PAs with amylose increased proportionally
      with molecular weight. For example, the percentage of PAs bound to amylose
      increased from 45% (PAs with degree of polymerization (DP) = 6) to 94% (polymeric
      PAs, DP > 10). The results demonstrate that molecular weight of the PAs directly
      affects their interaction with starch: the higher the molecular weight, the
      stronger the binding to amylose and the higher the RS formation. CONCLUSION:
      Polymeric PAs from sorghum can naturally modify starch by interacting strongly
      with amylose and are thus most suitable to produce foods with higher RS.

PMID- 24105769
TI  - Bayesian age-period-cohort models with versatile interactions and long-term
      predictions: mortality and population in Finland 1878-2050.
AB  - Age-period-cohort (APC) models are widely used for studying time trends of
      disease incidence or mortality. Model identifiability has become less of a
      problem with Bayesian APC models. These models are usually based on random walk
      (RW1, RW2) smoothing priors. For long and complex time series and for long
      predicted periods, these models as such may not be adequate. We present two
      extensions for the APC models. First, we introduce flexible interactions between
      the age, period and cohort effects based on a two-dimensional conditional
      autoregressive smoothing prior on the age/period plane. Our second extension uses
      autoregressive integrated (ARI) models to provide reasonable long-term
      predictions. To illustrate the utility of our model framework, we provide
      stochastic predictions for the Finnish male and female population, in 2010-2050.
      For that, we first study and forecast all-cause male and female mortality in
      Finland, 1878-2050, showing that using an interaction term is needed for fitting
      and interpreting the observed data. We then provide population predictions using
      a cohort component model, which also requires predictions for fertility and
      migration. As our main conclusion, ARI models have better properties for
      predictions than the simple RW models do, but mixing these prediction models with
      RW1 or RW2 smoothing priors for observed periods leads to a model that is not
      fully consistent. Further research with our model framework will concentrate on
      using a more consistent model for smoothing and prediction, such as
      autoregressive integrated moving average models with state-space methods or
      Gaussian process priors.

PMID- 24105771
TI  - Asymmetric conjugate addition of malonate esters to alpha,beta-unsaturated N
      sulfonyl imines: an expeditious route to chiral delta-aminoesters and
      piperidones.
AB  - The asymmetric conjugate addition of malonate esters to alpha,beta-unsaturated N
      sulfonyl imines is catalyzed by PyBOX/La(OTf)3 complexes in the presence of 4 A
      MS. The reaction gives the corresponding E enamines bearing a stereogenic center
      at the allylic position with good yields and enantiomeric ratios up to 97:3. This
      reaction provides a synthetic entry to chiral delta-aminoesters and piperidones. 

PMID- 24105770
TI  - Multiplex mapping of chromatin accessibility and DNA methylation within targeted
      single molecules identifies epigenetic heterogeneity in neural stem cells and
      glioblastoma.
AB  - Human tumors are comprised of heterogeneous cell populations that display diverse
      molecular and phenotypic features. To examine the extent to which epigenetic
      differences contribute to intratumoral cellular heterogeneity, we have developed
      a high-throughput method, termed MAPit-patch. The method uses multiplexed
      amplification of targeted sequences from submicrogram quantities of genomic DNA
      followed by next generation bisulfite sequencing. This provides highly scalable
      and simultaneous mapping of chromatin accessibility and DNA methylation on single
      molecules at high resolution. Long sequencing reads from targeted regions
      maintain the structural integrity of epigenetic information and provide
      substantial depth of coverage, detecting for the first time minority
      subpopulations of epigenetic configurations formerly obscured by existing genome
      wide and population-ensemble methodologies. Analyzing a cohort of 71 promoters of
      genes with exons commonly mutated in cancer, MAPit-patch uncovered several
      differentially accessible and methylated promoters that are associated with
      altered gene expression between neural stem cell (NSC) and glioblastoma (GBM)
      cell populations. In addition, considering each promoter individually,
      substantial epigenetic heterogeneity was observed across the sequenced molecules,
      indicating the presence of epigenetically distinct cellular subpopulations. At
      the divergent MLH1/EPM2AIP1 promoter, a locus with three well-defined, nucleosome
      depleted regions (NDRs), a fraction of promoter copies with inaccessible
      chromatin was detected and enriched upon selection of temozolomide-tolerant GBM
      cells. These results illustrate the biological relevance of epigenetically
      distinct subpopulations that in part underlie the phenotypic heterogeneity of
      tumor cell populations. Furthermore, these findings show that alterations in
      chromatin accessibility without accompanying changes in DNA methylation may
      constitute a novel class of epigenetic biomarker. 

PMID- 24105772
TI  - The psymberin story--biological properties and approaches towards total and
      analogue syntheses.
AB  - Psymberin is a marine natural product which has attracted a great deal of
      interest since its isolation: While the highly cytotoxic compound was detected
      early on as an ingredient in a marine sponge, it took over a decade and 600
      additional samples for the structure to eventually be assigned. In the last eight
      years fascinating synthetic and biosynthetic investigations have led to a more
      detailed understanding as well as a new starting point for structure-activity
      studies towards new antitumor compounds. The Review gives an in-depth insight
      into the progress in the field of the marine polyketide psymberin and
      demonstrates how organic synthesis is influencing neighboring scientific
      subjects. 

PMID- 24105773
TI  - Fetal kidneys: additional sonographic criteria of normal development.
AB  - OBJECTIVE: The aim of this study was to establish objective criteria for the
      evaluation of cortical echogenicity (CE), cortical thickness (CT), and medullary
      thickness (MT), as well as the corticomedullary ratio (CMR), throughout
      gestation. METHOD: In this prospective single-center study, CE, MT, CT, and CMR
      were evaluated in a group of singleton pregnancies examined by ultrasound during
      the second and third trimesters. RESULTS: The CE evolved from a hyperechoic
      pattern compared with the liver or spleen during early second trimester to a
      hypoechogenic pattern in the third trimester, with no fetus displaying cortical
      hyperechogenicity after 32 weeks. CT increased from 1.8 to 2.5 mm (p < 0.05) from
      21 to 25 to 34 to 37 weeks; MT from 2.7 to 5.1 mm (p < 0.0001), and the CMR
      decreased from 0.7 to 0.5 (p < 0.001). CONCLUSION: The CE, CT, and MT evolve with
      gestation. Cortical hyperechogenicity compared with the liver or spleen after 32
      weeks or a CMR above 0.7 in the third trimester should raise the suspicion of a
      fetal nephropathy.

PMID- 24105774
TI  - Cognitive processing in relation to psychological distress in women with breast
      cancer: a theoretical approach.
AB  - OBJECTIVE: To evaluable a cognitive procession model developed by Creamer and
      colleagues, this study examined the longitudinal relationship between intrusion
      and psychological distress, via avoidance, in women with breast cancer. METHODS:
      Participants included 189 patients who were newly diagnosed with breast cancer.
      The longitudinal association between intrusion, avoidance and psychological
      distress and the mediating role of avoidance between intrusion and psychological
      distress were examined. Intrusion was measured at inclusion (T1), avoidance at 3
      months post-inclusion (T2) and psychological distress at 12 months post-inclusion
      (T3). RESULTS: Results suggested that avoidance at T2 did not mediate the
      relationship between intrusions at T1 and psychological distress at T3.
      CONCLUSION: The results did not provide support for Creamer's model in an early
      stage breast cancer population, which suggests that early-stage breast cancer
      patient's process trauma differently from late-stage cancer patients. Therefore,
      it might be suggested that early-stage and late-stage cancer patients require
      different types of support and treatment for the distress experienced.

PMID- 24105775
TI  - Prevalence and molecular characterization of G1P[8] human rotaviruses possessing
      DS-1-like VP6, NSP4, and NSP5/6 in Japan.
AB  - During a survey of human rotaviruses in Okayama Prefecture, Japan in the 2011
      2012 rotavirus season (between September 2011 and August 2012), G3P[8] was found
      to be a predominant genotype overall. However, G1P[8] emerged in the latter half
      of the season. To clarify the genetic background of the G1P[8] strains, the VP7,
      VP4, VP6, NSP4, and NSP5/6 genes of the strains were sequenced and genotyped. As
      a result, it was demonstrated that the strains with two different genotype
      constellations (G1-P[8]-I1-E1-H1 and G1-P[8]-I2-E2-H2) prevailed in the season.
      The G1P[8] strains possessing the DS-1-like VP6, NSP4, and NSP5/6 genes (the DS-1
      like G1P[8] strains), which should reveal a short electropherotype, were
      originated from possible intergenogroup reassortment events. The DS-1-like G1P[8]
      strains accounted for 74.1% of all G1P[8] strains and were detected continuously
      throughout the season but not in the preceding season, indicating the possibility
      of new introduction and rapid spreading of these strains in the 2011-2012 season.
      The results suggest that the intergenogroup reassortants, considered generally
      unstable, can spread rapidly and become relevant.

PMID- 24105776
TI  - Modeling metal bioaccumulation and tissue distribution in killifish (Fundulus
      heteroclitus) in three contaminated estuaries.
AB  - The present study experimentally assessed the uptake, loss, and resulting tissue
      distribution of As(V), Cd, Cr(III), Hg(II), and methylmercury (MeHg) in killifish
      (Fundulus heteroclitus) following aqueous exposure in water collected from 3
      contaminated field sites-Baltimore Harbor and Elizabeth River (Chesapeake Bay),
      and Mare Island (San Francisco Bay)-using a radiotracer technique. Uptake rate
      constants (L g-1 d-1) were highest for MeHg (0.370-0.781) and lowest for As
      (0.00028-0.00065). Loss rate constants (d-1) were highest for As (0.046-0.096)
      and lowest for MeHg (0.006-0.009). Tissue distribution data showed that MeHg was
      redistributed around the body throughout the 9-d depuration period, and drinking
      may be an uptake mechanism for Cd from the aqueous phase in higher-salinity
      water. The kinetic parameters calculated in the present study were entered into a
      bioaccumulation model to calculate the predicted body burden of each metal at
      steady state and the percentage body burden attributable to dietary exposure on a
      site-specific basis. Calculated body burdens varied between field sites for all
      metals except Cr. The predicted values for Cd, Hg(II), and MeHg matched
      independent field data from contaminated estuaries, indicating that the model can
      account for the major processes governing metal concentration in killifish. The
      diet accounted for >97% of the body burden of Cd and MeHg and was the predominant
      exposure route for As and Cr.

PMID- 24105777
TI  - Dynamics of human milk nutrient composition of women from Singapore with a
      special focus on lipids.
AB  - BACKGROUND: A recent report suggested that human milk (HM) composition not only
      changes with lactation stages but also vary according to gender of the offspring.
      In spite of available literature, the dynamic changes of HM composition still
      remain to be completely explored and characterized. Progress in analytical
      technologies together with quantitative sampling of HM allows for a better
      quantification of HM nutrients and thereby providing a deeper understanding of
      the dynamics of HM secretion. OBJECTIVE: To characterize and quantify HM
      nutrients based on appropriate for analyses sampling procedures and advanced
      analytical methodologies. CLINICAL STUDY DESIGN: We conducted an observatory,
      single center, longitudinal trial with HM collection at 30, 60, and 120 days
      postpartum from 50 mothers (singleton-deliveries of 25 male and 25 female
      infants). HM samples were analyzed for lipid, lactose, energy density, fatty
      acids, phospholipids, and gangliosides. Longitudinal analyses of the datasets
      have been carried out using linear mixed models. RESULTS: HM for male infants
      compared to females at 120 days, were higher for energy content and lipids by 24
      and 39%, respectively. Similarly, other bioactive lipids such as linoleic acid,
      phospholipids and gangliosides were also significantly different based on the
      gender of the infant. Significant stage-based differences were observed for total
      lipids, energy density, phospholipids, and gangliosides. Such difference in HM
      composition may stem from different energy needs to cope up for individual growth
      and development. CONCLUSION: Collectively, the current observations affirm that
      HM secretion, especially the lipid composition, is a very dynamic and
      personalized biological process.

PMID- 24105779
TI  - Identification of pivotal cellular factors involved in HPV-induced dysplastic and
      neoplastic cervical pathologies.
AB  - Cervical carcinoma represents the paradigm of virus-induced cancers, where
      virtually all cervical cancers come from previous "high-risk" HPV infection. The
      persistent expression of the HPV viral oncoproteins E6 and E7 is responsible for
      the reprogramming of fundamental cellular functions in the host cell, thus
      generating a noticeable, yet only partially explored, imbalance in protein
      molecular networks and cell signaling pathways. Eighty-eight cellular factors,
      identified as HPV direct or surrogate targets, were chosen and monitored in a
      retrospective analysis for their mRNA expression in HPV-induced cervical lesions,
      from dysplasia to cancer. Real-time quantitative PCR (qPCR) was performed by
      using formalin-fixed, paraffin embedded archival samples. Gene expression
      analysis identified 40 genes significantly modulated in LSIL, HSIL, and squamous
      cervical carcinoma. Interestingly, among these, the expression level of a panel
      of four genes, TOP2A, CTNNB1, PFKM, and GSN, was able to distinguish between
      normal tissues and cervical carcinomas. Immunohistochemistry was also done to
      assess protein expression of two genes among those up-regulated during the
      transition between dysplasia and carcinoma, namely E2F1 and CDC25A, and their
      correlation with clinical parameters. Besides the possibility of significantly
      enhancing the use of some of these factors in diagnostic or prognostic
      procedures, these data clearly outline specific pathways, and thus key biological
      processes, altered in cervical dysplasia and carcinoma. Deeper insight on how
      these molecular mechanisms work may help widen the spectrum of novel innovative
      approaches to these virus-induced cell pathologies.

PMID- 24105778
TI  - Mothers' own recollections of being parented and risk of offspring depression 18
      years later: a prospective cohort study.
AB  - BACKGROUND: Although the relationship between maternal bonding and risk of
      offspring depression has been demonstrated, it is unclear whether this risk
      exists for subsequent generations. This study examines the association between
      maternal reports of her own mother's parenting and later risk of depression in
      offspring at age 18. METHOD: This study is based on data from the Avon
      Longitudinal Study of Parents and Children. Mothers enrolled in the study,
      completed the Parental Bonding Instrument to provide an assessment of how they
      were parented by their own mothers up to the age of 16. Offspring depression was
      assessed at age of 18 using the Clinical Interview Schedule-Revised. The sample
      comprised 10,405 respondents who had completed the Parental Bonding Instrument
      during the antenatal period. Results were adjusted for grandmother's history of
      depression, maternal depression, and a range of socioeconomic variables. RESULTS:
      A one standard deviation increase in mothers' perceived lack of care in their own
      childhood was associated with a 16% increase in the odds of offspring depression
      at age 18 (odds ratios = 1.16, 95% confidence intervals = [1.04, 1.30]). This
      effect remained following adjustment for potential confounders (odds ratios =
      1.14, 95% confidence intervals = [1.02, 1.27]). There was no evidence for an
      association between overprotection and offspring depression. CONCLUSIONS: This
      study is consistent with the hypothesis that sensitive caregiving is important to
      future risk of depression across generations. Preventative interventions could be
      aimed at promoting positive parenting practices, which may help to reduce the
      risk of depression in subsequent generations.

PMID- 24105780
TI  - Is early surveillance with CT scan necessary in patients with stage II/III
      colorectal cancer: a retrospective study.
AB  - BACKGROUND AND OBJECTIVES: This analysis aims to evaluate the value of early
      surveillance within 6 months after resection for stage II/III colorectal cancer
      (CRC). METHODS: Patients with stage II/III CRC who received surgery with curative
      intent for CRC were included. CT scans of the chest, abdomen, and pelvis
      performed within 6 months after surgery were evaluated. RESULTS: Among 150
      patients included in the study, 10 patients (1 occurred in stage II disease and 9
      occurred in stage III) were diagnosed as recurrence within 6 months after
      surgery. The proportion of patients diagnosed as recurrence was significantly
      higher in stage III disease than in stage II disease (P = 0.01). The likelihood
      of recurrence within 6 months was associated with the extent of lymph node
      metastases (r = 0.205, P = 0.012). Three patients with recurrent disease
      underwent salvage resection with curative intent. CONCLUSIONS: Early surveillance
      with CT scan within 6 months after curative resection may not be necessary for
      stage II disease. Although, the strategy may be helpful for stage III disease
      considering the high incidence of salvage surgery for recurrence disease, the
      early detection of recurrence could not be translated into survival benefit.

PMID- 24105781
TI  - Hydrogenated TiO(2) nanocrystals: a novel microwave absorbing material.
AB  - Here, we report, for the first time, hydrogenated TiO2 nanocrystals as a novel
      and exciting microwave absorbing material, based on an innovative collective
      movement-of-interfacial-dipole mechanism which causes collective-interfacial
      polarization-amplified microwave absorption at the crystalline/disordered and
      anatase/rutile interfaces. This mechanism is intriguing and upon further
      exploration may trigger other new concepts and applications. 

PMID- 24105782
TI  - Luminescent amphiphilic 2,6-bis(1,2,3-triazol-4-yl)pyridine-platinum(II)
      complexes: synthesis, characterization, electrochemical, photophysical, and
      Langmuir-Blodgett film-formation studies.
AB  - A new series of platinum(II) complexes with tridentate ligands 2,6-bis(1-alkyl
      1,2,3-triazol-4-yl)pyridine and 2,6-bis(1-aryl-1,2,3-triazol-4-yl)pyridine (N7R),
      [Pt(N7R)Cl]X (1-7) and [Pt(N7R)(C?CR')]X (8-17; R=n-C4 H9 , n-C8 H17 , n-C12 H25
      , n-C14 H29 , n-C18 H37 , C6 H5 , and CH2 -C6 H5 ; R'=C6 H5 , C6 H4 -CH3 -p, C6
      H4 -CF3 -p, C6 H4 -N(CH3 )2 -p, and cholesteryl 2-propyn-1-yl carbonate; X=OTf(-)
      , PF6 (-) , and Cl(-) ), has been synthesized and characterized. Their
      electrochemical and photophysical properties have also been studied. Two
      amphiphilic platinum(II)?2,6-bis(1-dodecyl-1,2,3-triazol-4-yl)pyridine complexes
      (3-Cl and 8) were found to form stable and reproducible Langmuir-Blodgett (LB)
      films at the air/water interface. These LB films were characterized by the study
      of their surface-pressure-molecular-area (pi-A) isotherms, XRD, and IR and
      polarized-IR spectroscopy. 

PMID- 24105784
TI  - Airway algorithm for the management of patients with a King LT.
AB  - OBJECTIVES/HYPOTHESIS: To discuss an algorithm for managing the airway in
      patients presenting with a King LT in place. STUDY DESIGN: Case series at a
      single institution with planned chart review. METHODS: This study reviewed the
      management of three patients who presented to a tertiary academic medical
      facility emergency department following placement of a King LT at an outside
      hospital or in the field. Clinical history at admission as well as each patient's
      hospital course was evaluated. We discuss the management of the airway in each of
      these cases and use these to help design an algorithm for improving outcomes in
      patients with a King LT in place. RESULTS: In each of the three cases presented,
      the Otolaryngology Department was consulted for definitive airway management. In
      two of these patients, the airway was successfully secured using endotracheal
      intubation. Only one patient required tracheostomy. We discuss an algorithm for
      managing these patients to obtain a safe airway, which includes assessing the
      airway with flexible endoscopy and then proceeding with intubation by the
      Seldinger technique or intubation using a video laryngoscope. In some cases,
      tracheostomy will be required to definitively secure the airway. CONCLUSIONS: The
      King LT is a valuable tool available in the field to help to temporarily secure
      the airway. Otolaryngologists should have an appropriate airway algorithm for
      managing patients with a King LT in place to minimize the need for a
      tracheostomy.

PMID- 24105783
TI  - Hygiene, atopy and wheeze-eczema-rhinitis symptoms in schoolchildren from urban
      and rural Ecuador.
AB  - BACKGROUND: Rural residence is protective against atopy and wheeze-rhinitis
      eczema symptoms in developed countries, an effect attributed to farming and poor
      hygiene exposures. There are few data from developing countries addressing this
      question. We compared atopy and wheeze-rhinitis-eczema symptoms between urban and
      rural Ecuador, and explored the effects of farming and poor hygiene exposures.
      METHODS: We performed cross sectional studies of schoolchildren living in rural
      and urban Ecuador. Data on symptoms and farming/hygiene exposures were collected
      by parental questionnaire, atopy by allergen skin prick test reactivity and
      geohelminth infections by stool examinations. RESULTS: Among 2526 urban and 4295
      rural schoolchildren, prevalence was: atopy (10.0% vs 12.5%, p=0.06), wheeze
      (9.4% vs 10.1%, p=0.05), rhinitis (8.1% vs 6.4%, p=0.02) and eczema (5.9% vs
      4.7%, p=0.06). A small proportion of symptoms were attributable to atopy (range
      3.9-10.7%) with greater attributable fractions for respiratory symptoms observed
      in urban schoolchildren. Respiratory symptoms were associated with poor
      hygiene/farming exposures: wheeze with lack of access to potable water; and
      rhinitis with household pets, no bathroom facilities and contact with large farm
      animals. Birth order was inversely associated with respiratory symptoms. Area of
      residence and atopy had few effects on these associations. CONCLUSIONS: Urban
      schoolchildren living in Ecuador have a similar prevalence of atopy, eczema and
      wheeze but a higher prevalence of rhinitis compared with rural children. Some
      farming and poor hygiene exposures were associated with an increase in the
      prevalence of wheeze or rhinitis while birth order was inversely associated with
      these symptoms.

PMID- 24105785
TI  - Genus-specific PCR assay for screening Arcobacter spp. in chicken meat.
AB  - BACKGROUND: The number of emerging pathogenic species described within the genus
      Arcobacter has increased rapidly during the last few years. In this work a genus
      specific polymerase chain reaction (PCR) assay was developed for detection of the
      species of Arcobacter most commonly associated with foods. The assay uses primers
      designed to amplify an 85 bp DNA fragment on the 16S rRNA gene and was applied to
      the detection of Arcobacter spp. in retail chicken meat. RESULTS: Primer
      specificity was tested against a panel of Arcobacter spp., related Campylobacter
      and Helicobacter spp. and other food bacteria. Arcobacter primers consistently
      and selectively amplified the expected DNA fragment in all tested Arcobacter spp.
      Bacterial control primers confirmed the presence of amplifiable DNA in the
      samples. The applicability of the PCR assay to food was validated through
      screening of fresh retail chicken samples for the presence of Arcobacter spp.,
      with a result of 45% (23 out of 51) positive samples. CONCLUSION: The genus
      specific PCR assay developed has the potential to be used as a quick and
      sensitive alternative method for the survey of Arcobacter contamination in meats.

PMID- 24105787
TI  - Viral etiology of influenza-like illnesses during the influenza season between
      December 2011 and April 2012.
AB  - The aim of this study was to determine the frequency of respiratory viruses
      responsible for respiratory tract infections in Turkish children during the 2011
      2012 influenza season. Nasal swabs were obtained from patients with symptoms
      suggestive of an influenza-like illness between December 2011 and April 2012.
      Samples were analyzed with multiplex real-time polymerase chain reaction (RT-PCR)
      to help identify the causative viral pathogen. A total of 200 patients were
      enrolled in the study. A respiratory virus was detected successfully in 102 (51%)
      children; influenza A (H3N2) in 39.2%, influenza B in 23.5%, RSV in 15.6%,
      rhinovirus in 13.7%, bocavirus in 2.9%, coronavirus in 2.9%, and metapneumovirus
      in 0.9% of patients. Only one patient was co-infected with bocavirus and
      influenza A virus. A statistically significant difference in the mean age of
      presentation was observed between the various viral pathogens (P < 0.001).
      Patients with RSV were significantly younger whereas children infected with the
      influenza viruses were significantly older. Comparison of symptoms revealed that
      fever and headache occurred more frequently with the influenza viruses than the
      other viruses combined (P < 0.001, <0.05). Durations of symptoms such as fever,
      cough, nasal congestion, and rhinorrhea were also significantly longer in the
      influenza group (P < 0.001, <0.005, <0.001, <0.005, respectively). Demographic
      analyses revealed that the school/daycare attendance was the only parameter
      associated with a significantly increased risk for influenza infection. With an
      overall viral pathogen detection rate of 51%, findings of the present study
      suggest other respiratory pathogens, whether viral or bacterial, may also lead to
      hospital visits due to influenza-like illnesses in children.

PMID- 24105788
TI  - Prevalence of depression in cancer patients: a meta-analysis of diagnostic
      interviews and self-report instruments.
AB  - OBJECTIVE: We aimed to investigate the prevalence of depression in cancer
      patients assessed by diagnostic interviews and self-report instruments, and to
      study differences in prevalence between type of instrument, type of cancer and
      treatment phase. METHODS: A literature search was conducted in four databases to
      select studies on the prevalence of depression among adult cancer patients during
      or after treatment. A total of 211 studies met the inclusion criteria. Pooled
      mean prevalence of depression was calculated using Comprehensive Meta-Analysis.
      RESULTS: Hospital Anxiety and Depression Scale-depression subscale (HADS-D) >= 8,
      HADS-D >=11, Center for Epidemiologic Studies >= 16, and (semi-)structured
      diagnostic interviews were used to define depression in 66, 53, 35 and 49
      studies, respectively. Respective mean prevalence of depression was 17% (95% CI =
      16-19%), 8% (95% CI = 7-9%), 24% (95% CI = 21-26%), and 13% (95% CI = 11-15%) (p
      < 0.001). Prevalence of depression ranged from 3% in patients with lung cancer to
      31% in patients with cancer of the digestive tract, on the basis of diagnostic
      interviews. Prevalence of depression was highest during treatment 14% (95% CI =
      11-17%), measured by diagnostic interviews, and 27% (95% CI = 25-30%), measured
      by self-report instruments. In the first year after diagnosis, prevalence of
      depression measured with diagnostic interviews and self-report instruments were
      9% (95% CI = 7-11%) and 21% (95% CI = 19-24%), respectively, and they were 8%
      (95% CI = 5-12%) and 15% (95% CI = 13-17%) >= 1 year after diagnosis.
      CONCLUSIONS: Pooled mean prevalence of depression in cancer patients ranged from
      8% to 24% and differed by the type of instrument, type of cancer and treatment
      phase. Future prospective studies should disentangle whether differences in
      prevalence of depression are caused by differences in the type of instrument,
      type of cancer or treatment phase. (c) 2013 The Authors. Psycho-Oncology
      published by John Wiley & Sons, Ltd.

PMID- 24105789
TI  - Longitudinal follow-up study of adolescents who report a suicide attempt: aspects
      of suicidal behavior that increase risk of a future attempt.
AB  - BACKGROUND: Previous studies have noted that a past suicide attempt (SA) predicts
      a future SA, but few studies have reported whether previous SAs that predict a
      future attempt differ from those that do not. Knowing which characteristics of
      previous SAs predict future attempts would assist in evaluating adolescents at
      risk of attempt repetition. This longitudinal study of an unreferred sample
      examined which characteristics of adolescent SAs increased risk for repeat
      attempts. METHODS: Fifty-four adolescents who had attempted suicide were
      identified through a two-stage screening of 1,729 high school students.
      Adolescents reported details of their past SA on the Adolescent Suicide Interview
      and were reassessed 4-6 years later by telephone. RESULTS: Eighteen of the 54
      teens (33%) reported that they had made another SA since baseline, and 17 of
      these reported characteristics of their later attempt. The odds of a further
      attempt were significantly increased by being alone (OR = 6.1, 95% CI = 1.1
      34.8), retrospectively reporting a serious wish to die (OR = 5.2, 95% CI = 1.2
      22.7), and planning the attempt for an hour or more (OR = 5.1, 95% CI = 1.1
      25.0). The method of attempt remained consistent from baseline to follow-up
      attempt (kappa = .67). CONCLUSIONS: Screening high school students to identify
      those who are at risk for making future SAs should include questions about number
      of previous SAs and such indicators of risk as isolation, wish to die, and extent
      of planning prior to a SA.

PMID- 24105790
TI  - Natural selection in Utero: evidence from the Great East Japan Earthquake.

PMID- 24105791
TI  - Proteomic profiling identified multiple short-lived members of the central
      proteome as the direct targets of the addicted oncogenes in cancer cells.
AB  - "Oncogene addiction" is an unexplained phenomenon in the area of cancer targeted
      therapy. In this study, we have tested a hypothesis that rapid apoptotic response
      of cancer cells following acute inhibition of the addicted oncogenes is because
      of loss of multiple short-lived proteins whose activity normally maintain cell
      survival by blocking caspase activation directly or indirectly. It was shown that
      rapid apoptotic response or acute apoptosis could be induced in both A431 and
      MiaPaCa-2 cells, and quick down-regulation of 17 proteins, which were all members
      of the central proteome of human cells, was found to be associated with the onset
      of acute apoptosis. Knockdown of PSMD11 could partially promote the occurrence of
      acute apoptosis in both MiaPaCa-2 and PANC-1 pancreatic cancer cells. These
      findings indicate that maintaining the stability of central proteome may be a
      primary mechanism for addicted oncogenes to maintain the survival of cancer cells
      through various signaling pathways, and quick loss of some of the short-lived
      members of the central proteome may be the direct reason for the rapid apoptotic
      response or acute apoptosis following acute inhibition of the addicted oncogenes
      in cancer cells. These findings we have presented can help us better understand
      the phenomenon of oncogene-addiction and may have important implications for the
      targeted therapy of cancer. 

PMID- 24105792
TI  - Protein microarray characterization of the S-nitrosoproteome.
AB  - Nitric oxide (NO) mediates a substantial part of its physiologic functions via S
      nitrosylation, however the cellular substrates for NO-mediated S-nitrosylation
      are largely unknown. Here we describe the S-nitrosoproteome using a high-density
      protein microarray chip containing 16,368 unique human proteins. We identified
      834 potentially S-nitrosylated human proteins. Using a unique and highly specific
      labeling and affinity capture of S-nitrosylated proteins, 138 cysteine residues
      on 131 peptides in 95 proteins were determined, defining critical sites of NO's
      actions. Of these cysteine residues 113 are novel sites of S-nitrosylation. A
      consensus sequence motif from these 834 proteins for S-nitrosylation was
      identified, suggesting that the residues flanking the S-nitrosylated cysteine are
      likely to be the critical determinant of whether the cysteine is S-nitrosylated.
      We identify eight ubiquitin E3 ligases, RNF10, RNF11, RNF41, RNF141, RNF181,
      RNF208, WWP2, and UBE3A, whose activities are modulated by S-nitrosylation,
      providing a unique regulatory mechanism of the ubiquitin proteasome system. These
      results define a new and extensive set of proteins that are susceptible to NO
      regulation via S-nitrosylation. Similar approaches could be used to identify
      other post-translational modification proteomes. 

PMID- 24105794
TI  - Toxicity of pesticides associated with potato production, including soil
      fumigants, to snapping turtle eggs (Chelydra serpentina).
AB  - Turtles frequently oviposit in soils associated with agriculture and, thus, may
      be exposed to pesticides or fertilizers. The toxicity of a pesticide regime that
      is used for potato production in Ontario on the survivorship of snapping turtle
      (Chelydra serpentina) eggs was evaluated. The following treatments were applied
      to clean soil: 1) a mixture of the pesticides chlorothalonil, S-metolachlor,
      metribuzin, and chlorpyrifos, and 2) the soil fumigant metam sodium. Turtle eggs
      were incubated in soil in outdoor plots in which these mixtures were applied at
      typical and higher field application rates, where the eggs were subject to
      ambient temperature and weather conditions. The pesticide mixture consisting of
      chlorothalonil, S-metolachlor, metribuzin, and chlorpyrifos did not affect
      survivorship, deformities, or body size at applications up to 10 times the
      typical field application rates. Hatching success ranged between 87% and 100% for
      these treatments. Metam sodium was applied at 0.1- times, 0.3- times, 1 times,
      and 3 times field application rates. Eggs exposed to any application of metam
      sodium had 100% mortality. At typical field application rates, the chemical
      regime associated with potato production does not appear to have any detrimental
      impacts on turtle egg development, except for the use of the soil fumigant metam
      sodium, which is highly toxic to turtle eggs at the lowest recommended
      application rate.

PMID- 24105795
TI  - A computational study of the mechanism of hydrogen evolution by cobalt(diimine
      dioxime) catalysts.
AB  - Cobalt(diimine-dioxime) complexes catalyze hydrogen evolution with low
      overpotentials and remarkable stability. In this study, DFT calculations were
      used to investigate their catalytic mechanism, to demonstrate that the initial
      active state was a Co(I) complex and that H2 was evolved in a heterolytic manner
      through the protonation of a Co(II)-hydride intermediate. In addition, these
      catalysts were shown to adjust their electrocatalytic potential for hydrogen
      evolution to the pH value of the solution and such a property was assigned to the
      presence of a H(+)-exchange site on the oxime bridge. It was possible to
      establish that protonation of the bridge was directly involved in the H2
      evolution mechanism through proton-coupled electron-transfer steps. A consistent
      mechanistic scheme is proposed that fits the experimentally determined
      electrocatalytic and electrochemical potentials of cobalt(diimine-dioxime)
      complexes and reproduces the observed positive shift of the electrocatalytic
      potential with increasing acidity of the proton source.

PMID- 24105796
TI  - Enhanced photoelectrochemical activity in all-oxide heterojunction devices based
      on correlated "metallic" oxides.
AB  - n-n Schottky, n-n ohmic, and p-n Schottky heterojunctions based on TiO2
      /correlated "metallic" oxide couples exhibit strong solar-light absorption driven
      by the unique electronic structure of the "metallic" oxides. Photovoltaic and
      photocatalytic responses are driven by hot electron injection from the "metallic"
      oxide into the TiO2 , enabling new modalities of operation for energy systems. 

PMID- 24105797
TI  - Catalytic functionalization of C(sp2)-H and C(sp3)-H bonds by using bidentate
      directing groups.
AB  - C-H bonds are ubiquitous in organic compounds. It would, therefore, appear that
      direct functionalization of substrates by activation of C-H bonds would eliminate
      the multiple steps and limitations associated with the preparation of
      functionalized starting materials. Regioselectivity is an important issue because
      organic molecules can contain a wide variety of C-H bonds. The use of a directing
      group can largely overcome the issue of regiocontrol by allowing the catalyst to
      come into proximity with the targeted C-H bonds. A wide variety of functional
      groups have been evaluated for use as directing groups in the transformation of C
      H bonds. In 2005, Daugulis reported the arylation of unactivated C(sp(3))-H bonds
      by using 8-aminoquinoline and picolinamide as bidentate directing groups, with
      Pd(OAc)2 as the catalyst. Encouraged by these promising results, a number of
      transformations of C-H bonds have since been developed by using systems based on
      bidentate directing groups. In this Review, recent advances in this area are
      discussed.

PMID- 24105793
TI  - Pathway modulations and epigenetic alterations in ovarian tumorbiogenesis.
AB  - Cellular pathways are numerous and are highly integrated in function in the
      control of cellular systems. They collectively regulate cell division,
      proliferation, survival and apoptosis of cells and mutagenesis of key genes that
      control these pathways can initiate neoplastic transformations. Understanding
      these pathways is crucial to future therapeutic and preventive strategies of the
      disease. Ovarian cancers are of three major types; epithelial, germ-cell, and
      stromal. However, ovarian cancers of epithelial origin, arising from the
      mesothelium, are the predominant form. Of the subtypes of ovarian cancer, the
      high-grade serous tumors are fatal, with low survival rate due to late detection
      and poor response to treatments. Close examination of preserved ovarian tissues
      and in vitro studies have provided insights into the mechanistic changes
      occurring in cells mediated by a few key genes. This review will focus on
      pathways and key genes of the pathways that are mutated or have aberrant
      functions in the pathology of ovarian cancer. Non-genetic mechanisms that are
      gaining prominence in the pathology of ovarian cancer, miRNAs and epigenetics,
      will also be discussed in the review.

PMID- 24105798
TI  - Otolaryngology and medical malpractice: A review of the past decade, 2001-2011.
AB  - OBJECTIVES/HYPOTHESIS: To better understand the causes and outcomes of lawsuits
      involving otolaryngologists in the past decade by analyzing malpractice
      litigation trends to prevent future litigation and improve physician education.
      STUDY DESIGN: Analysis of a national database for all US civil trials. METHODS:
      The Westlaw database was reviewed from 2001 to 2011. Data were compiled on the
      demographics of the plaintiffs, use of expert witnesses, procedures, nature of
      the injury, legal allegations, verdicts, and indemnities. RESULTS: One hundred
      ninety-eight cases met inclusion criteria. Verdicts for the
      defendant/otolaryngologist predominated (58%), whereas the average award when the
      verdict favored the plaintiff was $1,782,514. When otolaryngologists were used as
      expert witnesses by the defense, the verdict outcome statistically favored the
      defendant. Two of the most commonly cited legal allegations were improper
      performance and failure to diagnose and treat. Fifty-one cases involved
      allegations of wrongful death, with the overall outcome favoring the plaintiffs
      (51%). The average indemnities in these cases were significantly higher for
      plaintiff verdicts at $2,552,580 versus settlements at $992,896. Forty-two cases
      involved malignancy, with the two most common allegations being failure to
      diagnose and treat (79%) and delay in diagnosis (74%). CONCLUSIONS: Our study
      reveals that in the past decade, in significant malpractice litigations, overall
      outcomes favored otolaryngologists. The average awards was significantly higher
      when cases involved malignancy. Our analysis reveals the importance of meticulous
      surgical techniques and thorough preoperative evaluations. Last, when
      otolaryngologists are defendants in litigation, our review reiterates the value
      of the otolaryngologist as the defense's expert witnesses.

PMID- 24105799
TI  - Differential responses to JNJ-37822681, a specific and fast dissociating dopamine
      D2 receptor antagonist, in cynomolgus monkey and Sprague-Dawley rat general
      toxicology studies: clinical observations, prolactin levels, mammary
      histopathology findings and toxicokinetics.
AB  - JNJ-37822681 is a potent, specific and fast dissociating dopamine D2 receptor
      antagonist intended for the treatment of schizophrenia. Its nonclinical
      toxicological profile was investigated in a series of general repeat dose
      toxicity studies in cynomolgus monkeys and Sprague-Dawley rats. The maximum
      duration of treatment was 9 and 6 months, respectively. Interspecies differences
      were noted in the response to JNJ-37822681 in terms of extrapyramidal (EPS)-like
      clinical signs and prolactin-mediated tissue changes in the mammary gland.
      Monkeys showed severe EPS-like clinical signs such as abnormal posture, abnormal
      eye movements and hallucination-like behavior at relatively low exposures
      compared to those associated with EPS in patients with schizophrenia. The high
      sensitivity of the monkey to JNJ-37822681-induced EPS-like signs was unexpected
      based on the fast dissociating properties of the compound. Rats, however, were
      not prone to EPS. Elevated serum prolactin levels were found in rats and monkeys.
      While rats showed slight to moderate prolactin-related tissue changes upon
      histopathological examination in all studies, which among others affected the
      mammary gland, only minor mammary gland tissue changes were noted in monkeys.
      Prolactin levels were only slightly increased in patients with schizophrenia
      receiving relatively high dose levels of JNJ-37822681. The monkey toxicology
      studies did not provide an exposure-based safety margin, while in rats adverse
      effects were only noted at exposures considerably higher than those achieved at
      efficacious plasma concentrations in the clinic. Overall, the available data
      suggest that the cynomolgus monkey showed better predictivity towards the nature
      of JNJ-37822681-associated adverse events in humans than the Sprague-Dawley rat.

PMID- 24105800
TI  - Field camera measurements of gradient and shim impulse responses using frequency
      sweeps.
AB  - PURPOSE: Applications of dynamic shimming require high field fidelity, and
      characterizing the shim field dynamics is therefore necessary. Modeling the
      system as linear and time-invariant, the purpose of this work was to measure the
      impulse response function with optimal sensitivity. THEORY AND METHODS: Frequency
      swept pulses as inputs are analyzed theoretically, showing that the sweep speed
      is a key factor for the measurement sensitivity. By adjusting the sweep speed it
      is possible to achieve any prescribed noise profile in the measured system
      response. Impulse response functions were obtained for the third-order shim
      system of a 7 Tesla whole-body MR scanner. Measurements of the shim fields were
      done with a dynamic field camera, yielding also cross-term responses. RESULTS:
      The measured shim impulse response functions revealed system characteristics such
      as response bandwidth, eddy currents and specific resonances, possibly of
      mechanical origin. Field predictions based on the shim characterization were
      shown to agree well with directly measured fields, also in the cross-terms.
      CONCLUSION: Frequency sweeps provide a flexible tool for shim or gradient system
      characterization. This may prove useful for applications involving dynamic
      shimming by yielding accurate estimates of the shim fields and a basis for
      setting shim pre-emphasis.

PMID- 24105801
TI  - Solvent-accessible surface area: How well can be applied to hot-spot detection?
AB  - A detailed comprehension of protein-based interfaces is essential for the
      rational drug development. One of the key features of these interfaces is their
      solvent accessible surface area profile. With that in mind, we tested a group of
      12 SASA-based features for their ability to correlate and differentiate hot- and
      null-spots. These were tested in three different data sets, explicit water MD,
      implicit water MD, and static PDB structure. We found no discernible improvement
      with the use of more comprehensive data sets obtained from molecular dynamics.
      The features tested were shown to be capable of discerning between hot- and null
      spots, while presenting low correlations. Residue standardization such as rel
      SASAi or rel/res SASAi , improved the features as a tool to predict
      DeltaDeltaGbinding values. A new method using support machine learning algorithms
      was developed: SBHD (Sasa-Based Hot-spot Detection). This method presents a
      precision, recall, and F1 score of 0.72, 0.81, and 0.76 for the training set and
      0.91, 0.73, and 0.81 for an independent test set.

PMID- 24105802
TI  - Comparison of the toxicity of fluoridation compounds in the nematode
      Caenorhabditis elegans.
AB  - Fluorides are commonly added to drinking water in the United States to decrease
      the incidence of dental caries. Silicofluorides, such as sodium
      hexafluorosilicate (Na2 SiF6 ) and fluorosilicic acid (H2 SiF6 ), are mainly used
      for fluoridation, although fluoride salts such as sodium fluoride (NaF) are also
      used. Interestingly, only the toxicity of NaF has been examined and not that of
      the more often used silicofluorides. In the present study, the toxicities of NaF,
      Na2 SiF6 , and H2 SiF6 were compared. The toxicity of these fluorides on the
      growth, feeding, and reproduction in the alternative toxicological testing
      organism Caenorhabditis elegans was examined. Exposure to these compounds
      produced classic concentration-response toxicity profiles. Although the effects
      of the fluoride compounds varied among the 3 biological endpoints, no differences
      were found between the 3 compounds, relative to the fluoride ion concentration,
      in any of the assays. This suggests that silicofluorides have similar toxicity to
      NaF.

PMID- 24105803
TI  - Characterization of recombinant Zea mays transglutaminase expressed in Pichia
      pastoris and its impact on full and non-fat yoghurts.
AB  - BACKGROUND: Transglutaminases catalyze post-translational modification of
      proteins by epsilon-(gamma-glutamyl) links and covalent amide bonds. Research on
      properties and applications of plant transglutaminases is less developed than in
      animals and micro-organisms. In a previous study, optimized Zea mays
      transglutaminase was purified from recombinant Pichia pastoris strain. The main
      objective of the present study was to characterize this enzyme and assess its
      effect on the properties of yoghurt. RESULTS: The purified recombinant
      transglutaminase presented a Km of 3.98 umol L(-1) and a Vmax of 2711 min(-1) by
      the fluorometric method. The enzyme was stable after incubation for 30 min below
      50  degrees C and over a broad pH range of 5-8 at -20  degrees C for 12 h. The
      results showed that the crosslinking reaction catalyzed by this enzyme could
      effectively improve the properties of full and non-fat yoghurts. Also, the
      properties of non-fat yoghurt could be improved similar to the full-fat product
      by recombinant transglutaminase. CONCLUSION: The application of recombinant
      transglutaminase in yoghurt indicated that this enzyme could be used as a
      substitute for microbial transglutaminase in the production of yoghurt, thus
      providing experimental evidence for the future application of plant
      transglutaminases in the food industry.

PMID- 24105804
TI  - Splenectomy to treat splenic lesions: an analysis of 148 cases at a cancer
      center.
AB  - BACKGROUND AND OBJECTIVES: Solid and cystic splenic masses discovered on imaging
      studies often pose diagnostic and management dilemmas. This study analyses a
      large series of splenectomies to identify preoperative factors associated with
      malignant splenic masses. METHODS: Pathology records at a single institution were
      reviewed for all splenectomies. Those performed as a component of a larger
      resection, such as staging or debulking were excluded. Demographic and
      clinicopathologic factors were obtained. Univariate and multivariate analyses
      identified factors associated with an increased risk of malignancy. RESULTS:
      Between 1986 and 2012, 2,743 patients underwent a splenectomy, 148 of which were
      performed for lesions identified on imaging. The indications were suspicion of
      malignancy (120, 81%), growth over time (28, 19%), or symptoms (39, 26%).
      Resected splenic lesions were malignant in 93 patients (63%); the most common
      pathologies included ovarian cancer (n = 39), melanoma (n = 14), and colorectal
      cancer (n = 9). On multivariate analysis of clinicopathologic factors, a previous
      history of cancer was the only independent predictor of malignancy in the splenic
      lesion (odds ratio 6.3; 95% CI, 2.32-16.97; P = 0.001). CONCLUSION: While the
      spleen is an uncommon site of metastatic disease, in patients with a history of
      cancer, splenic masses selected for resection are frequently malignant.

PMID- 24105805
TI  - Polycation liposomes as a vector for potential intracellular delivery of
      microRNA.
AB  - BACKGROUND: We previously developed a microRNA (miRNA) delivery system by using
      dicetyl phosphate-tetraethylenepentamine-based polycation liposomes (TEPA-PCL),
      applied it to miR-92a delivery, and demonstrated its gene-silencing potential and
      effective anti-angiogenic effects. In the present study, we investigated the
      mechanism of intracellular delivery of cholesterol-grafted miR-92a (miR-92a-C)
      into cells. METHODS: To investigate the intracellular distribution of miR-92a
      C/TEPA-PCL complex, we used human umbilical vein endothelial cells and examined
      certain points after transfection: (i) the time-course of miR-92a-uptake into the
      cells; (ii) the endocytosis pathway induced by miR-92a-C/TEPA-PCL; (iii) the
      capability of miR-92a-C/TEPA-PCL to escape from the endosomes; and (iv) the
      release of miR-92a-C from TEPA-PCL in the cytoplasm. RESULTS: Our data indicated
      that miR-92a-C formulated in TEPA-PCL accumulated in and was spread throughout
      the cytoplasm in a time-dependent manner, and was taken up into the cells by
      macropinosome-mediated endocytosis. In addition, the surface charge of miR-92a
      C/TEPA-PCL was neutral at pH 7.4 and was charged positively at around pH 5.5,
      which is the inner pH of endosomes. When the late endosomes/lysosomes were
      stained with Lysotracker, miR-92a-C/TEPA-PCL efficiently escaped from the
      endosomes into the cytoplasm, possibly through the proton-sponge effect.
      Furthermore, miR-92a-C spread throughout whole cytoplasm and did not co-localize
      completely with TEPA-PCL, indicating that some of the miR-92a-C was present in
      free form in the cytoplasm. CONCLUSIONS: The results of the present study suggest
      that TEPA-PCL-based lipoplexes have an excellent potential to deliver microRNAs
      into the cytoplasm of cells and to induce RNA silencing action mediated by
      microRNAs and other small RNAs.

PMID- 24105806
TI  - Hippocampal shape analysis in Alzheimer's disease using functional data analysis.
AB  - The hippocampus is one of the first affected regions in Alzheimer's disease. The
      left hippocampi of control subjects, patients with mild cognitive impairment and
      patients with Alzheimer's disease are represented by spherical harmonics.
      Functional data analysis is used in the hippocampal shape analysis. Functional
      principal component analysis and functional independent component analysis are
      defined for multivariate functions with two arguments. A functional linear
      discriminant function is also defined. Comparisons with other approaches are
      carried out. Our functional approach gives promising results, especially in shape
      classification.

PMID- 24105807
TI  - Anatomical and computed tomographic analysis of the transcochlear and endoscopic
      transclival approaches to the petroclival region.
AB  - OBJECTIVES/HYPOTHESIS: Advances in the field of skull base surgery aim to
      maximize anatomical exposure while minimizing patient morbidity. The petroclival
      region of the skull base presents numerous challenges for surgical access due to
      the complex anatomy. The transcochlear approach to the region provides adequate
      access; however, the resection involved sacrifices hearing and results in at
      least a grade 3 facial palsy. An endoscopic endonasal approach could potentially
      avoid negative patient outcomes while providing a desirable surgical window in a
      select patient population. STUDY DESIGN: Cadaveric study. METHODS: Endoscopic
      access to the petroclival region was achieved through an endonasal approach. For
      comparison, a transcochlear approach to the clivus was performed. Different
      facets of the dissections, such as bone removal volume and exposed surface area,
      were computed using computed tomography analysis. RESULTS: The endoscopic
      endonasal approach provided a sufficient corridor to the petroclival region with
      significantly less bone removal and nearly equivalent exposure of the surgical
      target, thus facilitating the identification of the relevant anatomy. The lateral
      approach allowed for better exposure from a posterolateral direction until the
      inferior petrosal sinus; however, the endonasal approach avoided
      labyrinthine/cochlear destruction and facial nerve manipulation while providing
      an anteromedial viewpoint. The endonasal approach also avoided external incisions
      and cosmetic deficits. The endonasal approach required significant sinonasal
      resection. CONCLUSIONS: Endoscopic access to the petroclival region is a feasible
      approach. It potentially avoids hearing loss, facial nerve manipulation, and
      cosmetic damage.

PMID- 24105808
TI  - Multivalency in the gas phase: H/D exchange reactions unravel the dynamic "rock
      'n' roll" motion in dendrimer-dendrimer complexes.
AB  - Noncovalent dendrimer-dendrimer complexes were successfully ionized by
      electrospray ionization of partly protonated amino-terminated polypropylene amine
      (POPAM) and POPAM dendrimers fully functionalized with benzo[21]crown-7 on all
      branches. Hydrogen/deuterium exchange (HDX) experiments conducted on dendrimer
      dendrimer complexes in the high vacuum of a mass spectrometer give rise to a
      complete exchange of all labile NH hydrogen atoms. As crown ethers represent
      noncovalent protective groups against HDX reactions on the ammonium group to
      which they are coordinated, this result provides evidence for a very dynamic
      binding situation: each crown is mobile enough to move from one ammonium binding
      site to another. Schematically, one might compare this motion with two rock 'n'
      roll dancers that swirl around each other without completely losing all contact
      at any time. Although the multivalent attachment certainly increases the overall
      affinity, the "microdynamics" of individual site binding and dissociation remains
      fast. 

PMID- 24105809
TI  - N-linked polylactosamine glycan synthesis is regulated by co-expression of
      beta3GnT2 and GCNT2.
AB  - Poly-N-acetyllactosamine (PLN) is a unique glycan composed of repeating units of
      the common disaccharide (Galbeta1,4-GlcNAcbeta1,3)n . The expression of PLN on
      glycoprotein core structures minimally requires enzyme activities for beta1,4
      galactosyltransferase (beta4GalT) and beta1,3-N-acetylglucosminyltransferase
      (beta3GnT). Because beta4GalTs are ubiquitous in most cells, PLN expression is
      generally ascribed to the tissue-specific transcription of eight known beta3GnT
      genes in mice. In the olfactory epithelium (OE), beta3GnT2 regulates expression
      of extended PLN chains that are essential for axon guidance and neuronal
      survival. N-glycan branching and core composition, however, can also modulate the
      extent of PLN modification. Here, we show for the first time that the beta1,6
      branching glycosyltransferase GCNT2 (formerly known as IGnT) is expressed at high
      levels specifically in the OE and other sensory ganglia. Postnatally, GCNT2 is
      maintained in mature olfactory neurons that co-express beta3GnT2 and PLN. This
      highly specific co-expression suggests that GCNT2 and beta3GnT2 function
      cooperatively in PLN synthesis. In support of this, beta3GnT2 and GCNT2 co
      transfection in HEK293T cells results in high levels of PLN expression on the
      cell surface and on adenylyl cyclase 3, a major carrier of PLN glycans in the OE.
      These data clearly suggest that GCNT2 functions in vivo together with beta3GnT2
      to determine PLN levels in olfactory neurons by regulating beta1,6-branches that
      promote PLN extension.

PMID- 24105810
TI  - Chemical activity of thin oxide layers: strong interactions with the support
      yield a new thin-film phase of ZnO.

PMID- 24105811
TI  - The influence of dispositional optimism on decision regret to undergo major
      breast reconstructive surgery.
AB  - BACKGROUND & OBJECTIVES: It is not known if optimism influences regret following
      major reconstructive breast surgery. We examined the relationship between
      dispositional optimism, major complications and decision regret in patients
      undergoing microsurgical breast reconstruction. METHODS: A consecutive series of
      290 patients were surveyed. Independent variables were: (1) dispositional
      optimism and (2) major complications. The primary outcome was Decision Regret. A
      multivariate regression analysis determined the relationship between the
      independent variables, confounders and decision regret. RESULTS: Of the 181
      respondents, 63% reported no regret after breast reconstruction, 26% had mild
      regret, and 11% moderate to severe regret. Major complications did not have a
      significant effect on decision regret, and the impact of dispositional optimism
      was not significant in Caucasian women. There was a significant effect in non
      Caucasian women with less optimism who had significantly higher levels of mild
      regret 1.36 (CI 1.02-1.97) and moderate to severe regret 1.64 (CI 1.0-93.87).
      CONCLUSIONS: This is the first paper to identify a subgroup of non-Caucasian
      patients with low dispositional optimism who may be at risk for developing regret
      after microsurgical breast reconstruction. Possible strategies to ameliorate
      regret may involve addressing cultural and language barriers, setting realistic
      expectations, and providing more support during the pre-operative decision-making
      phase.

PMID- 24105812
TI  - Persistence of estrogenic activity in soils following land application of
      biosolids.
AB  - Estrogenic compounds may enter the environment when biosolids are applied to
      land. In the present study, soil samples were collected over 4 mo from a field
      trial following addition of biosolids. The recombinant yeast estrogen screen
      bioassay identified estrogenic activity in the soil at all sampling times to
      concentrations up to 2.3 ug 17beta-estradiol equivalency/kg. The present results
      indicate the potential for estrogenic compounds to persist in soil following
      biosolids application.

PMID- 24105813
TI  - Laryngeal electromyography as a diagnostic tool for Parkinson's disease.
AB  - OBJECTIVES/HYPOTHESIS: To study the laryngeal electromyography pattern in
      patients with Parkinson's disease (PD) and vocal complaints at different stages
      of the disease. STUDY DESIGN: Cross-sectional cohort study. METHODS: Ninety-four
      adults with PD and vocal complaints at different stages of the disease (according
      to the Hoehn and Yahr scale) underwent laryngeal electromyography. RESULTS:
      Tremors were not detected on laryngeal electromyography of the cricothyroid and
      thyroarytenoid muscles even in patients with clinical tremor. Laryngeal
      electromyography hypercontractility during voice rest was the typical result
      observed in 91.5% of patients regardless of disease severity. Gender and age of
      subjects did not correlate with laryngeal electromyography results. Patients with
      PD presented spontaneous intrinsic laryngeal muscle activity during voice rest,
      regardless of disease severity. CONCLUSIONS: This study was significant because
      it reported on the use of laryngeal electromyography in a large number of
      patients with PD and vocal complaints grouped according to PD severity. The
      patterns observed suggest that laryngeal electromyography is a valuable
      diagnostic tool for PD even at early phases of the disease.

PMID- 24105814
TI  - Thermally stable autonomic healing in epoxy using a dual-microcapsule system.
AB  - Self-healing is achieved with a dual-microcapsule system utilizing epoxy-amine
      chemistry in a high temperature cured thermosetting epoxy polymer. One capsule
      contains a modified aliphatic polyamine prepared by vacuum infiltration of
      polyoxypropylenetriamine into hollow polymeric microcapsules. The second capsule
      contains a difunctional epoxide and reactive diluent. Healing efficiency is
      accessed through recovery of fracture toughness and excellent long-term stability
      at ambient conditions is demonstrated. 

PMID- 24105815
TI  - Application of the compressed sensing technique to self-gated cardiac cine
      sequences in small animals.
AB  - PURPOSE: Self-gated cine sequences are a common choice for cardiac MRI in
      preclinical applications. The aims of our work were to apply the compressed
      sensing technique to IntraGateFLASH cardiac MRI studies on rats and to find the
      maximum acceleration factor achievable with this technique. THEORY AND METHODS:
      Our reconstruction method extended the Split Bregman formulation to minimize the
      total variation in both space and time. In addition, we analyzed the influence of
      the undersampling pattern on the acceleration factor achievable. RESULTS: Our
      results show that acceleration factors of up to 15 are achievable with our
      technique when appropriate undersampling patterns are used. The introduction of a
      time-varying random sampling clearly improved the efficiency of the undersampling
      schemes. In terms of computational efficiency, the proposed reconstruction method
      has been shown to be competitive as compared with the fastest methods found in
      the literature. CONCLUSION: We successfully applied our compressed sensing
      technique to self-gated cardiac cine acquisition in small animals, obtaining an
      acceleration factor of up to 15 with almost unnoticeable image degradation.

PMID- 24105816
TI  - Development of luminescent coelenterazine derivatives activatable by beta
      galactosidase for monitoring dual gene expression.
AB  - Two bioluminogenic caged coelenterazine derivatives (bGalCoel and bGalNoCoel)
      were designed and synthesized to detect beta-galactosidase activity and
      expression by means of bioluminescence imaging. Our approach addresses the
      instability of coelenterazine by introducing beta-galactose caging groups to
      block the auto-oxidation of coelenterazine. Both probes contain beta
      galactosidase cleavable caging groups at the carbonyl group of the imidazo
      pyrazinone moiety. One of the probes in particular, bGalNoCoel, displayed a fast
      cleavage profile, high stability, and high specificity for beta-galactosidase
      over other glycoside hydrolases. bGalN-oCoel could detect beta-galactosidase
      activity in living HEK-293T cell cultures that expressed a mutant Gaussia
      luciferase. It was determined that coelenterazine readily diffuses in and out of
      cells after uncaging by beta-galactosidase. We showed that this new caged
      coelenterazine derivative, bGalNoCoel, could function as a dual-enzyme substrate
      and detect enzyme activity across two separate cell populations. 

PMID- 24105817
TI  - Prenatal exposure to bisphenol A at the reference dose impairs mitochondria in
      the heart of neonatal rats.
AB  - Bisphenol A (BPA) exposure has been reported to be epidemiologically associated
      with heart disease. As mitochondria play an important role in the early
      development of the heart and in the pathogenesis of heart disease, the current
      study investigated the possibility of cardiac mitochondrial injury in neonatal
      rat heart prenatally exposed to BPA. Pregnant Wistar rats were exposed to BPA 50
      ug kg(-1)  day(-1) or corn oil 1 ml kg(-1) by oral gavage throughout gestation.
      Heart samples from pups on postnatal day 1 were isolated for analysis.
      Ultrastructure results showed mild swelling with dissociation of cristae in
      myocardial mitochondria of BPA-treated rats. Additionally, mitochondrial membrane
      potential and the activity of respiratory chain complex II were significantly
      decreased. However, the activities of other three complexes (CI, CIII, CIV) and
      cardiac histology stayed normal. The expression levels of some key regulators
      involved in mitochondria energy metabolism and ATP-generating pathways were
      downregulated. The study demonstrated for the first time that prenatal exposure
      to BPA at the reference dose could impair mitochondria in the hearts of neonatal
      rats.

PMID- 24105818
TI  - Sizes of interface residues account for cross-class binding affinity patterns in
      Eph receptor-ephrin families.
AB  - Eph receptors comprise the largest known family of receptor tyrosine kinases in
      mammals. They bind members of a second family, the ephrins. As both Eph receptors
      and ephrins are membrane bound, interactions permit unusual bidirectional cell
      cell signaling. Eph receptors and ephrins each form two classes, A and B, based
      on sequences, structures, and patterns of affinity: Class A Eph receptors bind
      class A ephrins, and class B Eph receptors bind class B ephrins. The only known
      exceptions are the receptor EphA4, which can bind ephrinB2 and ephrinB3 in
      addition to the ephrin-As (Bowden et al., Structure 2009;17:1386-1397); and
      EphB2, which can bind ephrin-A5 in addition to the ephrin-Bs (Himanen et al., Nat
      Neurosci 2004;7:501-509). A crystal structure is available of the interacting
      domains of the EphA4-ephrin B2 complex (wwPDB entry 2WO2) (Bowden et al.,
      Structure 2009;17:1386-1397). In this complex, the ligand-binding domain of EphA4
      adopts an EphB-like conformation. To understand why other cross-class EphA
      receptor-ephrinB complexes do not form, we modeled hypothetical complexes between
      (1) EphA4-ephrinB1, (2) EphA4-ephrinB3, and (3) EphA2-ephrinB2. We identify
      particular residues in the interface region, the size variations of which cause
      steric clashes that prevent formation of the unobserved complexes. The sizes of
      the sidechains of residues at these positions correlate with the pattern of
      binding affinity.

PMID- 24105819
TI  - Salinity source-induced changes in yield, mineral composition, phenolic acids and
      flavonoids in leaves of artichoke and cardoon grown in floating system.
AB  - BACKGROUND: Leaves of artichoke (Cynara cardunculus L. subsp. scolymus (L.) Hegi)
      and cardoon (Cynara cardunculus L. var. altilis DC) are traditionally used as
      herbal medicine. Moderate salt stress could enhance antioxidant activity and
      phytochemicals in leaves. The aim of this study was to evaluate the effect of
      chloride salts (NaCl, KCl and CaCl2) on biomass production, mineral composition,
      phenolic and flavonoid contents and antioxidant activity in leaves of artichoke
      and cardoon grown in a floating system. RESULTS: In both crops, NaCl and KCl
      treatments reduced biomass production, while similar values were recorded in
      CaCl2 and control treatments. In both crops, KCl treatment enhanced total
      phenolic and flavonoid contents, antioxidant activity and target polyphenols in
      leaves harvested at 48, 82 and 105 days after sowing (DAS), while leaf quality
      was improved by NaCl and CaCl2 treatments only at 82 and 105 DAS. Irrespective of
      salinity, leaves of cardoon had higher total phenolic and flavonoid contents,
      antioxidant activity and target polyphenols than those of artichoke. CONCLUSION:
      The results showed that application of KCl can be considered an effective way to
      produce high-quality leaves of artichoke and cardoon during the whole cropping
      cycle, although resulting in a 30% reduction in plant biomass.

PMID- 24105820
TI  - Targeted transgene insertion into the AAVS1 locus driven by baculoviral vector
      mediated zinc finger nuclease expression in human-induced pluripotent stem cells.
AB  - BACKGROUND: The AAVS1 locus is viewed as a 'safe harbor' for transgene insertion
      into human genome. In the present study, we report a new method for AAVS1
      targeting in human-induced pluripotent stem cells (hiPSCs). METHODS: We have
      developed two baculoviral transduction systems: one to deliver zinc finger
      nuclease (ZFN) and a DNA donor template for site-specific gene insertion and
      another to mediate Cre recombinase-mediated cassette exchange system to replace
      the inserted transgene with a new transgene. RESULTS: Our ZFN system provided the
      targeted integration efficiency of a Neo-EGFP cassette of 93.8% in G418-selected,
      stable hiPSC colonies. Southern blotting analysis of 20 AASV1 targeted colonies
      revealed no random integration events. Among 24 colonies examined for mono- or
      biallelic AASV1 targeting, 25% of them were biallelically modified. The selected
      hiPSCs displayed persistent enhanced green fluorescent protein expression and
      continued the expression of stem cell pluripotency markers. The hiPSCs maintained
      the ability to differentiate into three germ lineages in derived embryoid bodies
      and transgene expression was retained in the differentiated cells. After pre
      including the loxP-docking sites into the Neo-EGFP cassette, we demonstrated that
      a baculovirus-Cre/loxP system could be used to facilitate the replacement of the
      Neo-EGFP cassette with another transgene cassette at the AAVS1 locus.
      CONCLUSIONS: Given high targeting efficiency, stability in expression of inserted
      transgene and flexibility in transgene exchange, the approach reported in the
      present study holds potential for generating genetically-modified human
      pluripotent stem cells suitable for developmental biology research, drug
      development, regenerative medicine and gene therapy.

PMID- 24105821
TI  - Advanced multiplicity adjustment methods in clinical trials.
AB  - During the last decade, many novel approaches for addressing multiplicity
      problems arising in clinical trials have been introduced in the literature. These
      approaches provide great flexibility in addressing given clinical trial
      objectives and yet maintain strong control of the familywise error rate. In this
      tutorial article, we review multiple testing strategies that are related to the
      following: (a) recycling local significance levels to test hierarchically ordered
      hypotheses; (b) adapting the significance level for testing a hypothesis to the
      findings of testing previous hypotheses within a given test sequence, also in
      view of certain consistency requirements; (c) grouping hypotheses into
      hierarchical families of hypotheses along with recycling the significance level
      between those families; and (d) graphical methods that permit repeated recycling
      of the significance level. These four different methodologies are related to each
      other, and we point out some connections as we describe and illustrate them. By
      contrasting the main features of these approaches, our objective is to help
      practicing statisticians to select an appropriate method for their applications.
      In this regard, we discuss how to apply some of these strategies to clinical
      trial settings and provide algorithms to calculate critical values and adjusted p
      values for their use in practice. The methods are illustrated with several
      numerical examples.

PMID- 24105822
TI  - Small but smart: sensitive microgel capsules.
AB  - Microgel capsules are micrometer-sized particles that consist of a cross-linked
      and swollen polymer network complexed with additives. These capsules can be
      actuated by external stimulation if they are formed from sensitive or
      supramolecular polymer networks. To make this truly useful, it is crucial to
      control the microgel size, shape, and loading; this can be achieved by droplet
      based microfluidic templating. 

PMID- 24105823
TI  - Neurogenesis of neural crest-derived periodontal ligament stem cells by EGF and
      bFGF.
AB  - Neuroregenerative medicine is an ever-growing field in which regeneration of lost
      cells/tissues due to a neurodegenerative disease is the ultimate goal. With the
      scarcity of available replacement alternatives, stem cells provide an attractive
      source for regenerating neural tissue. While many stem cell sources exist,
      including: mesenchymal stem cells, embryonic stem cells, and induced pluripotent
      stem cells, the limited cellular potency, technical difficulties, and ethical
      considerations associated with these make finding alternate sources a desirable
      goal. Periodontal ligament stem cells (PDLSCs) derived from the neural crest were
      induced into neural-like cells using a combination of epidermal growth factor,
      and basic fibroblast growth factor. Morphological changes were evident in our
      treated group, seen under both light microscopy and scanning electron microscopy.
      A statistically significant increase in the expression of neuron-specific beta
      tubulin III and the neural stem/progenitor cell marker nestin, along with
      positive immunohistochemical staining for glial fibrillary acidic protein,
      demonstrated the success of our treatment in inducing both neuronal and glial
      phenotypes. Positive staining for synaptophysin demonstrated neural connections
      and electrophysiological recordings indicated that when subjected to whole-cell
      patch clamping, our treated cells displayed inward currents conducted through
      voltage-gated sodium (Na(+) ) channels. Taken together, our results indicate the
      success of our treatment in inducing PDLSCs to neural-like cells. The ease of
      sourcing and expansion, their embryologic neural crest origin, and the lack of
      ethical implications in their use make PDLSCs an attractive source for use in
      neuroregenerative medicine.

PMID- 24105824
TI  - Periconception maternal characteristics and embryonic growth trajectories: the
      Rotterdam Predict study.
AB  - STUDY QUESTION: Are maternal characteristics and lifestyle factors associated
      with human embryonic growth trajectories? SUMMARY ANSWER: Periconception maternal
      age is associated with increased, and smoking and alcohol use with decreased
      embryonic growth trajectories, estimated with crown-rump length (CRL)
      measurements. WHAT IS KNOWN ALREADY: Fetal weight is associated with health and
      disease in later life. Maternal characteristics and lifestyle factors affect
      fetal growth in the second and third trimesters of pregnancy and at birth;
      however, little is known about the association of these characteristics with
      first trimester embryonic growth. STUDY DESIGN, SIZE, DURATION: In a tertiary
      centre, pregnant women were recruited and enrolled in a prospective
      periconception cohort study before 8 weeks of gestation. We selected 87
      spontaneously conceived singleton pregnancies of women recruited in 2009 and 2010
      that ended in non-malformed live births. PARTICIPANTS/MATERIALS, SETTING,
      METHODS: We performed weekly three-dimensional ultrasound scans from enrolment up
      to 13 weeks of gestation. At enrolment, a questionnaire was completed. Embryonic
      CRL measurements were performed using the V-Scope software in the BARCO I-Space.
      Associations between maternal characteristics and embryonic growth were assessed
      using square root transformed CRL as response in linear mixed model analyses,
      adjusted for potential confounders. MAIN RESULTS AND THE ROLE OF CHANCE: Four
      hundred and ninety-six scans from 87 pregnancies were included. In the
      multivariable analysis, maternal age was positively associated with first
      trimester CRL (difference per maternal year of age 0.024?mm (95% confidence
      interval (CI) 0.009, 0.040), P = 0.001). At 6 and 12 weeks of gestation, the CRL
      of an embryo from a 40-year-old mother was estimated 2.0 mm (61%) and 7.2 mm
      (14%) larger, respectively, compared with an embryo from a 20-year-old mother.
      Smoking of 10 or more cigarettes per day was negatively associated with CRL
      (difference -0.211?mm (95% CI -0.416, -0.006), P = 0.04), with embryos that were
      0.9 mm (18.7%) and 3.1 mm (5.5%) smaller at 6 and 12 weeks, respectively,
      compared with non-smokers. Periconception alcohol use was negatively associated
      with CRL growth rate (difference -0.0025?mm (95% CI -0.0047, -0.0003)/day
      gestational age, P = 0.022), with embryos that were 0.2 mm (3%) and 1.1 mm (2%)
      smaller at 6 and 12 weeks, respectively, compared with non-alcohol users. Parity,
      BMI and moment of initiation of folic acid use were not significantly associated
      with embryonic CRL. LIMITATIONS, REASONS FOR CAUTION: Due to the selection of
      pregnancies in a tertiary centre and the small number of pregnancies, the
      external validity of the results has to be confirmed using larger sample sizes
      and other population-based periconception cohort studies. WIDER IMPLICATIONS OF
      THE FINDINGS: The association of maternal age and smoking with embryonic growth
      is in line with previous literature, whereas the association between embryonic
      growth and alcohol use is a new finding. However, concerning exposure to alcohol,
      the effect estimate was small and it is questionable whether this is of clinical
      value. More research is warranted to unravel underlying mechanisms and to assess
      the implications for preconception and early pregnancy care, such as the
      development and implementation of effective lifestyle interventions. STUDY
      FUNDING/COMPETING INTEREST(S): The work was funded by the Department of
      Obstetrics and Gynaecology, Erasmus MC, University Medical Centre, Rotterdam, The
      Netherlands. The authors declare no conflicts of interest.

PMID- 24105825
TI  - The role of knowledge and perceived susceptibility in intentions to optimize
      fertility: findings from the International Fertility Decision-Making Study
      (IFDMS).
AB  - STUDY QUESTION: What is the role of knowledge, perceived vulnerability and level
      of risk of infertility in women's intentions to take action to improve their
      chance of becoming pregnant (i.e. by seeking medical and/or non-medical help and
      making lifestyle changes)? SUMMARY ANSWER: Women younger than age 35 were more
      likely to intend to take measures to improve their chance of conceiving when they
      were knowledgeable about fertility and felt susceptible to infertility; however,
      there was no such association in older women. WHAT IS KNOWN ALREADY: The majority
      of young adults wish to become parents but many are jeopardizing their chances by
      engaging in behaviours that decrease fertility (e.g. smoking, not seeking timely
      medical advice when faced with problems conceiving). Research is needed to
      establish what motivates people to take steps to optimize their chances of
      pregnancy. The Health Belief Model (HBM) postulates that knowledge and beliefs
      about susceptibility to infertility are critical in whether people will engage in
      fertility-optimizing behaviours. STUDY DESIGN, SIZE AND DURATION: This cross
      sectional survey included 1345 childless women (trying to conceive and having
      never engaged in fertility medical treatment) from the International Fertility
      Decision-Making Study (IFDMS). PARTICIPANTS/MATERIALS, SETTING, METHODS:
      Infertility risk factors were determined using the FertiSTAT. The Cardiff
      Fertility Knowledge Scale (CFKS) assessed fertility knowledge. Perceived
      susceptibility was defined as whether a fertility problem was suspected. The
      outcome measure was intentions to optimize one's fertility by making lifestyle
      changes and/or seeking help. MAIN RESULTS AND THE ROLE OF CHANCE: In this study,
      75.5% of women had an infertility risk factor and 60.3% suspected a fertility
      problem. The average correct score on the CFKS was 51.9%. Intentions to optimize
      fertility were lower among women who were heavy smokers (P < 0.05) and who had
      been trying to conceive for a year or over (P < 0.01), while intentions to
      optimize fertility were greater among those with a higher body mass index or
      greater knowledge and those who suspected a fertility problem (all P < 0.001).
      These overall effects were qualified in some subgroups. Heavy smokers were more
      likely to intend to seek medical help when they had greater knowledge (P < 0.001)
      and women having difficulty conceiving were more likely to intend to seek medical
      help if they felt susceptible to infertility (P < 0.001). Heavy smokers who were
      knowledgeable intended to change their lifestyle only when they felt they had a
      fertility problem (P < 0.01). Intentions to change were not dependent on
      knowledge and perceived susceptibility in older women. LIMITATIONS, REASONS FOR
      CAUTION: The data were cross-sectional and thus we cannot infer causality. The
      results may have been affected by the sample profile, which was biased towards
      high levels of perceived susceptibility and low levels of knowledge. WIDER
      IMPLICATIONS OF THE FINDINGS: To maximize impact, educational campaigns should
      take into account the presence and type of infertility risk factors in the target
      audience. STUDY FUNDING/COMPETING INTERESTS: Merck-Serono S. A. Geneva
      Switzerland (an affiliate of Merck KGaA Darmstadt, Germany) and the Economic and
      Social Research Council (ESRC, UK) funded this project (RES-355-25-0038,
      'Fertility Pathways Network'). L.B. is funded by a postdoctoral fellowship from
      the Medical Research Council (MRC) and the ESRC (PTA-037-27-0192). B.F. is funded
      by an interdisciplinary PhD studentship from the ESRC/MRC (ES/1031790/1). I.T. is
      an employee of Merck-Serono S.A. Geneva-Switzerland (an affiliate of Merck KGaA
      Darmstadt, Germany).

PMID- 24105826
TI  - Drugs associated with teratogenic mechanisms. Part I: dispensing rates among
      pregnant women in the Netherlands, 1998-2009.
AB  - STUDY QUESTION: What are the dispensing rates of drugs suspected to be associated
      with teratogenic mechanisms among pregnant Dutch women? SUMMARY ANSWER: In a
      substantial proportion of pregnancies in our study population at least one drug
      associated with a teratogenic mechanism was dispensed in the first trimester of
      pregnancy. WHAT IS KNOWN ALREADY: The main teratogenic mechanisms of medical
      drugs that may affect fetal development in the first trimester of pregnancy have
      been described previously. However, information on the dispensing rate of such
      drugs among women at all stages of pregnancy is lacking. STUDY DESIGN, SIZE,
      DURATION: To determine how often medications suspected to be associated with a
      teratogenic mechanism are used by pregnant women, we studied 32 016 pregnancies
      included in the IADB.nl database between 1998 and 2009. PARTICIPANTS/MATERIALS,
      SETTING, METHODS: We estimated dispensing rates of medical drugs suspected to be
      associated with teratogenic mechanisms in our study population. The IADB.nl
      database includes all pharmacy dispensings for an estimated population of 220 000
      in 1994-1998 and c.500 000 since 1999. In addition, trends in first trimester
      dispensing rates over time and patterns of receiving multiple drugs associated
      with teratogenic mechanisms were evaluated. In addition, we determined the number
      of pregnancies in which multiple prescription drugs from one or more teratogenic
      categories were dispensed in the first trimester, and we evaluated the numbers of
      different medications dispensed that could be grouped within a specific
      teratogenic mechanism. MAIN RESULTS AND THE ROLE OF CHANCE: In 175 per 1000
      pregnancies [95% confidence interval (CI), 171-179] at least one drug associated
      with a teratogenic mechanism was dispensed in the first trimester. The total
      dispensing rate was 236 per 1000 pregnancies (95% CI 232-241) in the 3 months
      before pregnancy and an increasing trend was seen in the second [214 per 1000
      (95% CI 209-218)] and third [327 per 1000 (95% CI 322-332)] trimesters. The first
      trimester dispensing rates increased between 1998 and 2009 for selective
      serotonin-reuptake inhibitors (P < 0.001) and serotonin receptor
      agonists/antagonists (P < 0.001). In 71.8% of pregnancies in which drugs
      associated with teratogenic mechanisms were dispensed in the first trimester,
      women received drugs related to only one mechanism. Of the pregnancies in which
      drugs from multiple teratogenic categories were dispensed in the first trimester,
      1148 (72.6%) women received drugs from 2 categories, 317 (20.0%) from three
      categories, 88 (5.6%) from 4 categories, 28 (1.8%) from 5 categories and 1 from 6
      categories. Several women received multiple prescription medications grouped
      within a single teratogenic mechanism in the first trimester, ranging between
      13.3% for cyclo-oxygenase inhibitors and 41.8% for serotonin receptor
      agonists/antagonists. LIMITATIONS, REASONS FOR CAUTION: We used a dispensing
      database, therefore actual use of the medication prescribed is unknown and non
      compliance could have led to overestimation of exposure prevalences. WIDER
      IMPLICATIONS OF THE FINDINGS: Owing to the uncertainties concerning the safety of
      medication use during pregnancy, the results of this study stress the need for
      cautious prescription of medication associated with teratogenic mechanisms to
      women of reproductive age. This is further supported by our finding that women
      received multiple prescription medications grouped within a single teratogenic
      mechanism in the first trimester, which would theoretically increase strongly the
      risk of birth defects. STUDY FUNDING/COMPETING INTEREST(S): Marleen van Gelder
      was supported by the Netherlands Organisation for Scientific Research/NWO (grant
      no. 021.001.008). No competing interests are declared. TRIAL REGISTRATION NUMBER:
      N/A.

PMID- 24105827
TI  - Impact of the Irish smoking ban on sales in bars using a large business-level
      data set from 1999 to 2007.
AB  - BACKGROUND: Ireland introduced comprehensive smoke-free workplace legislation in
      2004. This study evaluates the economic impact of the workplace smoking ban on
      the value of sales in bars. METHODS: Data on the value of bar sales were derived
      from a large, nationally representative, annual business-level survey from 1999
      to 2007. The economic impact of the smoking ban was evaluated according to
      geographical region and bar size. Analysis was based on an econometric model
      which controlled for background changes in population income and wealth and for
      investments made by the bars during this period. RESULTS: The overall impact of
      the Irish smoking ban on bar sales appears to be very small. The ban was
      associated with an increase in sales among medium to large bars in the Border
      Midland-West (more rural) region of Ireland, and a small reduction in sales among
      large bars in the more urban, South-East region. We failed to find any evidence
      of a change in bar sales in the remaining categories studied. CONCLUSIONS: The
      results indicate that although some bars saw positive effects and some negative,
      the overall impact of the smoking ban on the value of sales in bars was
      negligible. These findings provide further supporting evidence that comprehensive
      smoke-free workplace legislation does not harm hospitality businesses while
      having positive health effects.

PMID- 24105828
TI  - The price sensitivity of cigarette consumption in Bangladesh: evidence from the
      International Tobacco Control (ITC) Bangladesh Wave 1 (2009) and Wave 2 (2010)
      Surveys.
AB  - BACKGROUND: In Bangladesh, the average excise tax on cigarettes accounted for
      just 38% of the average retail price of cigarettes in 2009, and 45% in 2010. Both
      these rates are well below the WHO recommended share of 70% of the retail price
      at a minimum. There is thus ample room for raising taxes on cigarettes in
      Bangladesh. The objective of the present work was therefore to estimate the price
      elasticity of demand for cigarettes and the effect of tax increases on the
      consumption of cigarettes and on tax revenue in Bangladesh. METHODS: Based on
      data from Wave 1 (2009) and Wave 2 (2010) of the International Tobacco Control
      Bangladesh Survey, we estimated the overall impact of a price change on cigarette
      demand using a two-part model. The total price elasticity of cigarettes was
      measured by the sum of the elasticity of smoking prevalence and the elasticity of
      average daily consumption conditional on smoking participation. The price
      elasticity estimates were used in a simulation model to predict changes in
      cigarette consumption and tax revenue from tax and price increases. RESULTS: The
      total price elasticity of demand for cigarettes was estimated at -0.49. The
      elasticity of smoking prevalence accounted for 59% of the total price elasticity.
      The price elasticity of cigarette consumption is higher for people belonging to
      lower socioeconomic status. Increases in taxes would result in a significant
      reduction in cigarette consumption while increasing tax revenue. CONCLUSIONS:
      Raising cigarette prices through increased taxation could lead to a win-win-win
      situation in Bangladesh: it would reduce cigarette consumption, increase tobacco
      tax revenue and potentially decrease socioeconomic inequities.

PMID- 24105829
TI  - Sieving polymer synthesis by reversible addition fragmentation chain transfer
      polymerization.
AB  - Replaceable sieving polymers are the fundamental component for high resolution
      nucleic acids separation in CE. The choice of polymer and its physical properties
      play significant roles in influencing separation performance. Recently,
      reversible addition fragmentation chain transfer (RAFT) polymerization has been
      shown to be a versatile polymerization technique capable of yielding well defined
      polymers previously unattainable by conventional free radical polymerization. In
      this study, a high molecular weight PDMA at 765 000 gmol-1 with a PDI of 1.55 was
      successfully synthesized with the use of chain transfer agent - 2-propionic
      acidyl butyl trithiocarbonate (PABTC) in a multi-step sequential RAFT
      polymerization approach. This study represents the first demonstration of RAFT
      polymerization for synthesizing polymers with the molecular weight range suitable
      for high resolution DNA separation in sieving electrophoresis. Adjustment of pH
      in the reaction was found to be crucial for the successful RAFT polymerization of
      high molecular weight polymer as the buffered condition minimizes the effect of
      hydrolysis and aminolysis commonly associated with trithiocarbonate chain
      transfer agents. The separation efficiency of PABTC-PDMA was found to have
      marginally superior separation performance compared to a commercial PDMA
      formulation, POPTM-CAP, of similar molecular weight range.

PMID- 24105830
TI  - Prevalence of human papillomaviruses in patients with head and neck squamous cell
      carcinoma in Lithuania and Belarus.
AB  - Overall, head and neck sqamous cell carcinoma accounts for more than 550,000
      cases annually worldwide. It is well known that human papillomavirus (HPV) is the
      main risk factor for cervical cancer development. As the incidence and the
      mortality of cervical cancer are closely related to the HPV prevalence, we
      hypothesized that there is the same association between HPV prevalence and head
      and neck squamous cell carcinoma. Therefore we performed the study aiming to
      compare the level of HPV infection and HPV type distribution between two groups
      of Lithuanian and Belarusian patients with head and neck sqamous cell carcinoma.
      One hundred ninety head and neck sqamous cell carcinoma patients were included in
      the study, 75 from Lithuania and 115 from Belarus. PCR was used for HPV detection
      and typing. The distribution of HPV infection among head and neck sqamous cell
      carcinoma patients was similar in the Lithuanian (20.0%) and Belarusian (18.3%)
      patient groups, however differences were found in the distribution of HPV types.

PMID- 24105831
TI  - Major transport mechanisms of pyrethroids in residential settings and effects of
      mitigation measures.
AB  - The major pathways for transport of pyrethroids were determined in runoff studies
      conducted at a full-scale test facility in central California, USA. The 6
      replicate house lots were typical of front lawns and house fronts of California
      residential developments and consisted of stucco walls, garage doors, driveways,
      and residential lawn irrigation sprinkler systems. Each of the 6 lots also
      included a rainfall simulator to generate artificial rainfall events. Different
      pyrethroids were applied to 5 surfaces-driveway, garage door and adjacent walls,
      lawn, lawn perimeter (grass near the house walls), and house walls above grass.
      The volume of runoff water from each house lot was measured, sampled, and
      analyzed to determine the amount of pyrethroid mass lost from each surface.
      Applications to 3 of the house lots were made using the application practices
      typically used prior to recent label changes, and applications were made to the
      other 3 house lots according to the revised application procedures. Results from
      the house lots using the historic application procedures showed that losses of
      the compounds applied to the driveway and garage door (including the adjacent
      walls) were 99.75% of total measured runoff losses. The greatest losses were
      associated with significant rainfall events rather than lawn irrigation events.
      However, runoff losses were 40 times less using the revised application
      procedures recently specified on pyrethroid labels.

PMID- 24105832
TI  - Electrolyte-gated organic field-effect transistor for selective reversible ion
      detection.
AB  - An ion-sensitive electrolyte-gated organic field-effect transistor for selective
      and reversible detection of sodium (Na(+) ) down to 10(-6) M is presented. The
      inherent low voltage - high current operation of these transistors in combination
      with a state-of-the-art ion-selective membrane proves to be a novel, versatile
      modular sensor platform. 

PMID- 24105833
TI  - Conservation analysis of class-specific positions in cytochrome P450
      monooxygenases: functional and structural relevance.
AB  - Cytochrome P450 monooxygenases (CYPs) constitute a ubiquitous, highly divergent
      protein family. Nevertheless, all CYPs share a common fold and conserved
      catalytic machinery. Based on the electron donor system, 10 classes of CYPs have
      been described, but most CYPs are members of class I accepting electrons from
      ferredoxin which is being reduced by FAD-containing reductase, or class II
      accepting electrons from FAD- and FMN-containing CPR-type reductase. Because of
      the low sequence conservation inside the two classes, the conserved class
      specific positions are expected to be involved in aspects of electron transfer
      that are specific to the two types of reductases. In this work we present results
      from a conservation analysis of 16,732 CYP sequences derived from an updated
      version of the Cytochrome P450 Engineering Database (CYPED), using two class
      specific numbering schemes. While no position was conserved on the distal,
      substrate-binding surface of the CYPs, several class-specific residues were found
      on the proximal, reductase-interacting surface; two class I-specific residues
      that were negatively charged, and three class II-specific residues that were
      aromatic or charged. The class-specific conservation of glycine and proline
      residues in the cysteine pocket indicates that there are class-specific
      differences in the flexibility of this element. Four heme-interacting arginines
      were conserved differently in each class, and a class-specific substitution of a
      heme-interacting tyrosine by histidine was found, pointing to a link between heme
      stabilization and the reductase type.

PMID- 24105834
TI  - Physicochemical and functional properties of beany flavour-free bambara groundnut
      protein isolate.
AB  - BACKGROUND: Off-odour/flavour (beany) associated with bambara groundnut protein
      isolate (BGPI), due to oxidative degradation of lipids during either storage or
      processing, is a major problem limiting its application in foods. In this study,
      effects of heat treatment (50-80  degrees C) in combination with
      ethylenediaminetetraacetic acid (EDTA) on functional and sensory properties of
      BGPI were investigated. RESULTS: BGPI prepared in the presence of EDTA had lower
      lipoxygenase and trypsin-inhibitory activities than BGPI prepared in the absence
      of EDTA, regardless of the heating temperature used (P < 0.05). Inactivation of
      lipoxygenase was associated with lowered peroxide value, thiobarbituric acid
      reactive substances and beany odour/flavour intensity in BGPI stored at room
      temperature for 30 days. BGPI with heat treatment at temperatures lower than 70 
      degrees C had similar protein patterns to BGPI prepared by the typical process,
      except for the occurrence of proteins with molecular weight 70-82 kDa. BGPI with
      heat treatment showed decreased protein solubility but increased surface
      hydrophobicity and sulfhydryl group content. BGPI prepared in the presence of
      EDTA exhibited higher emulsion activity and stability indices as well as higher
      foam expansion and stability than BGPI prepared in the absence of EDTA,
      regardless of heating temperature (P < 0.05). CONCLUSION: Heat treatment at 70 
      degrees C in the presence of 100 mmol L(-1) EDTA effectively reduced beany
      flavour development and enhanced the functionality of BGPI.

PMID- 24105835
TI  - Obese mice are resistant to eosinophilic airway inflammation induced by diesel
      exhaust particles.
AB  - Particulate matter can exacerbate respiratory diseases such as asthma. Diesel
      exhaust particles are the substantial portion of ambient particulate matter with
      a <2.5 um diameter in urban areas. Epidemiological data indicate increased
      respiratory health effects of particulate matter in obese individuals; however,
      the association between obesity and diesel exhaust particle-induced airway
      inflammation remains unclear. We aimed to investigate the differences in
      susceptibility to airway inflammation induced by exposure to diesel exhaust
      particles between obese mice (db/db) and lean mice (db/+m). Female db/db and
      db/+m mice were intratracheally administered diesel exhaust particles or vehicle
      every 2 weeks for a total of seven times. The cellular profile of bronchoalveolar
      lavage fluid and histological changes in the lungs were assessed and the lungs
      and serum were analyzed for the generation of cytokines, chemokines and soluble
      intercellular adhesion molecule 1. Diesel exhaust particle exposure-induced
      eosinophilic infiltration in db/+m mice accompanied by T-helper 2 cytokine,
      chemokine and soluble intercellular adhesion molecule 1 expression in the lungs.
      In contrast, it induced mild neutrophilic airway inflammation accompanied by
      elevated cytokines and chemokines in db/db mice. The lungs of db/db mice
      exhibited decreased expression of eosinophil activators/chemoattractants such as
      interleukin-5, interleukin-13 and eotaxin compared with those of db/+m mice. In
      addition, serum eotaxin and monocyte chemotactic protein-1 levels were
      significantly higher in db/db mice than in db/+m mice. In conclusion, obesity can
      affect susceptibility to diesel exhaust particle-induced airway inflammation,
      which is possibly due to differences in local and systemic inflammatory responses
      between lean and obese individuals.

PMID- 24105836
TI  - Sparse partial least-squares regression for high-throughput survival data
      analysis.
AB  - The partial least-square (PLS) method has been adapted to the Cox's proportional
      hazards model for analyzing high-dimensional survival data. But because the
      latent components constructed in PLS employ all predictors regardless of their
      relevance, it is often difficult to interpret the results. In this paper, we
      propose a new formulation of sparse PLS (SPLS) procedure for survival data to
      allow simultaneous sparse variable selection and dimension reduction. We develop
      a computing algorithm for SPLS by modifying an iteratively reweighted PLS
      algorithm and illustrate the method with the Swedish and the Netherlands Cancer
      Institute breast cancer datasets. Through the numerical studies, we find that our
      SPLS method generally performs better than the standard PLS and sparse Cox
      regression methods in variable selection and prediction.

PMID- 24105837
TI  - Otolith organ function according to subtype of benign paroxysmal positional
      vertigo.
AB  - OBJECTIVES/HYPOTHESIS: The clinical features and treatment outcomes of benign
      paroxysmal positional vertigo (BPPV) are known to be different depending on the
      type of and involved canal. This difference could be due to differences in the
      functional change of the otolith organ. STUDY DESIGN: Case series. METHODS: Forty
      nine patients were diagnosed to primary BPPV; 18 were categorized as posterior
      canal canalolithiasis (PC canalolithiasis), and 31 were categorized as horizontal
      canal (HC) BPPV with canalolithiasis or cupulolithiasis (HC canalolithiasis or HC
      cupulolithiasis). Diagnostic interventions to measure vestibular functions were
      performed such as electronystagmography (ENG), videonystagmography (VNG), and
      static and dynamic subjective visual vertical (SVV). BPPV was confirmed with
      nystagmus during positioning/positional test under ENG and VNG. Static SVV was
      recorded with a light-emitting diode (LED) bar located in front of the patients
      before eccentric rotation and dynamic SVV was recorded during eccentric rotation
      with the LED bar. SVV angles were read by the examiner and analyzed. The measured
      values were compared to those of normal controls and each other. RESULTS: Dynamic
      SVV toward the lesion side in all subtypes of BPPV were significantly different
      from those of the controls; HC cupulolithiasis showed significantly lower values
      than those of PC canalolithiasis and HC canalolithiasis. CONCLUSIONS: HC
      cupulolithiasis shows a lesser degree of utricular dysfunction compared with
      other subtypes. It could postulate the difference of pathophysiology between
      canalolithiasis and cupulolithiasis. LEVEL OF EVIDENCE: 4.

PMID- 24105839
TI  - Synthesis of densely functionalised 5-halogen-1,3-oxazin-2-ones by halogen
      mediated regioselective cyclisation of N-Cbz-protected propargylic amines: a
      combined experimental and theoretical study.
AB  - A very efficient synthesis of 5-halogen-1,3-oxazin-2-ones has been accomplished
      by the halocyclisation reaction of chiral nonracemic N-carbobenzyloxy (N-Cbz)
      protected propargylic amines by using I2, Br2 and Cl2 as electrophile sources.
      The nature of the halogen influences the reaction time and yield. However, in all
      cases the reaction is totally regioselective taking place through a 6-endo-dig
      process regardless of the nature of the halogen and of the substituents in the
      starting material. To rationalise the experimental results, theoretical studies
      at the B3LYP/6-311G* level have been performed.

PMID- 24105838
TI  - Improved susceptibility weighted imaging method using multi-echo acquisition.
AB  - PURPOSE: To introduce novel acquisition and postprocessing approaches for
      susceptibility weighted imaging (SWI) to remove background field inhomogeneity
      artifacts in both magnitude and phase data. METHODS: The proposed method acquires
      three echoes in a three-dimensional gradient echo (GRE) sequence, with a field
      compensation gradient (z-shim gradient) applied to the third echo. The artifacts
      in the magnitude data are compensated by signal estimation from all three echoes.
      The artifacts in phase signals are removed by modeling the background phase
      distortions using Gaussians. The method was applied in vivo and compared with
      conventional SWI. RESULTS: The method successfully compensates for background
      field inhomogeneity artifacts in magnitude and phase images, and demonstrated
      improved SWI images. In particular, vessels in frontal lobe, which were not
      observed in conventional SWI, were identified in the proposed method. CONCLUSION:
      The new method improves image quality in SWI by restoring signal in the frontal
      and temporal regions.

PMID- 24105840
TI  - Klebsiella pneumoniae meningitis induces memory impairment and increases pro
      inflammatory host response in the central nervous system of Wistar rats.
AB  - Klebsiella pneumoniae meningitis has recently become an increasingly common cause
      of central nervous system infection. The invasion of bacteria within the
      subarachnoid space stimulates the release of pro-inflammatory cytokines and
      chemokines, triggering a host immune response. The aim of the present study was
      to evaluate memory and pro-inflammatory mediators at different times in the
      brains of adult Wistar rats with K. pneumoniae meningitis. The animals were
      sacrificed at 6, 12, 24, 48 and 96 h after meningitis induction. The hippocampus,
      frontal cortex and cerebrospinal fluid were isolated to determine the cytokine,
      chemokine and brain-derived neurotrophic factor (BDNF) levels. In the first 6 and
      24 h following meningitis induction, there was a significant increase of the TNF
      alpha, IL-1beta, IL-6, cytokine-induced neutrophil chemoattractant-1 and BDNF
      levels in the central nervous system. Ten days after meningitis induction,
      cognitive memory was evaluated using an open-field task and step-down inhibitory
      avoidance task. In the control group, significant differences in behaviour were
      observed between the training and testing sessions for both tasks, demonstrating
      habituation and aversive memory. However, the meningitis group did not exhibit
      any difference between the training and testing sessions in either task,
      demonstrating memory impairment. As a result of these observations, we believe
      that the meningitis model may be a good research tool to study the biological
      mechanisms involved in the pathophysiology of this illness, while recognizing
      that animal models should be interpreted with caution before extrapolation to the
      clinic. 

PMID- 24105841
TI  - Campylobacter concisus and exotoxin 9 levels in paediatric patients with Crohn's
      disease and their association with the intestinal microbiota.
AB  - There is mounting evidence for a possible role for Campylobacter concisus in
      Crohn's disease (CD). However, the pathogenic potential of C. concisus remains
      disputed due to its presence in healthy subjects. It is documented that genetic
      diversity exists within this species, with some strains possessing putative
      virulence determinants such as exotoxin 9/DnaI that may enable them to persist
      intracellularly in host cells. In order to clarify this, we employed real-time
      PCR to determine C. concisus and exotoxin 9 levels within faecal samples of CD
      patients and healthy controls, and correlated these levels with abundances of
      microbial taxa identified in a subset of subjects. Both C. concisus and exotoxin
      9 levels were found to be higher in CD patients than healthy controls, suggesting
      not only that CD patients had a greater abundance of C. concisus but also that
      their strains were likely to be more virulent. Moreover, C. concisus levels
      correlated with the exotoxin 9 levels in CD patients but not in healthy controls,
      indicating that healthy controls were colonized by non-virulent C. concisus
      strains. Correlations with the intestinal microbiota found C. concisus levels to
      correlate with Eubacterium, Subdoligranulum and Blautia, while exotoxin 9 levels
      correlated with Dialister, Oscillospira, Lachnospira and Prevotella. This
      suggests that either the composition of the intestinal microbial flora has the
      ability to influence levels of both virulent and non-virulent C. concisus
      strains, or infection with C. concisus may modulate the levels of specific
      bacterial taxa within the gastrointestinal tract.

PMID- 24105842
TI  - Pathological findings and diagnostic implications of a rhesus macaque (Macaca
      mulatta) model of aerosol-exposure melioidosis (Burkholderia pseudomallei).
AB  - Aerosolized Burkholderia pseudomallei, the causative agent of melioidosis, can
      infect many species of mammals (including humans), causing rapid, severe
      pneumonia with high mortality. Diagnosis in humans is challenging, as few
      organisms can be detected in blood or other non-invasive samples. Although it
      cannot be said that the model is established, studies to date indicate that
      rhesus macaques may represent a good model of human melioidosis. This is
      supported by the results of this study. The early progression of meliodosis in
      the rhesus macaque was studied in an effort to better understand the disease and
      the application of rapid diagnostic methods. Results indicate that a PCR analysis
      of key diagnostic samples such as nasal swabs, throat swabs, tracheo bronchial
      lymph node aspirates and broncho-alveolar lavage may be a useful component of a
      rapid diagnostic algorithm in case of aerosol exposure. 

PMID- 24105843
TI  - Adaptive regulation of endothelin receptor type-A and type-B in vascular smooth
      muscle cells during pregnancy in rats.
AB  - Normal pregnancy is associated with systemic vasodilation and decreased vascular
      contraction, partly due to increased release of endothelium-derived vasodilator
      substances. Endothelin-1 (ET-1) is an endothelium-derived vasoconstrictor acting
      via endothelin receptor type A (ETA R) and possibly type B (ETB R) in vascular
      smooth muscle cells (VSMCs), with additional vasodilator effects via endothelial
      ETB R. However, the role of ET-1 receptor subtypes in the regulation of vascular
      function during pregnancy is unclear. We investigated whether the decreased
      vascular contraction during pregnancy reflects changes in the expression/activity
      of ETAR and ETBR. Contraction was measured in single aortic VSMCs isolated from
      virgin, mid-pregnant (mid-Preg, day 12), and late-Preg (day 19) Sprague-Dawley
      rats, and the mRNA expression, protein amount, tissue and cellular distribution
      of ETAR and ETBR were examined using RT-PCR, Western blots, immunohistochemistry,
      and immunofluorescence. Phenylephrine (Phe, 10(-5)  M), KCl (51 mM), and ET-1
      (10(-6)  M) caused VSMC contraction that was in late-Preg < mid-Preg and virgin
      rats. In VSMCs treated with ETB R antagonist BQ788, ET-1 caused significant
      contraction that was still in late-Preg < mid-Preg and virgin rats. In VSMCs
      treated with the ETAR antagonist BQ123, ET-1 caused a small contraction; and the
      ETBR agonists IRL-1620 and sarafotoxin 6c (S6c) caused similar contraction that
      was in late-Preg < mid-Preg and virgin rats. RT-PCR revealed similar ETAR, but
      greater ETBR mRNA expression in pregnant versus virgin rats. Western blots
      revealed similar ETAR, and greater protein amount of ETBR in endothelium-intact
      vessels, but reduced ETBR in endothelium-denuded vessels of pregnant versus
      virgin rats. Immunohistochemistry revealed prominent ETBR staining in the intima,
      but reduced ETAR and ETBR in the aortic media of pregnant rats.
      Immunofluorescence signal for ETAR and ETBR was less in VSMCs of pregnant versus
      virgin rats. The pregnancy-associated decrease in ETAR- and ETBR-mediated VSMC
      contraction appears to involve downregulation of ETAR and ETBR
      expression/activity in VSM, and may play a role in the adaptive vasodilation
      during pregnancy.

PMID- 24105845
TI  - RBE4 cells are highly resistant to paraquat-induced cytotoxicity: studies on
      uptake and efflux mechanisms.
AB  - Paraquat (PQ) is a widely used, highly toxic and non-selective contact herbicide,
      which has been associated with central neurotoxic effects, namely the development
      of Parkinson's disease, but whose effects to the blood-brain barrier (BBB) itself
      have rarely been studied. This work studied the mechanisms of PQ uptake and
      efflux in a rat's BBB cell model, the RBE4 cells. PQ is believed to enter cells
      using the basic or neutral amino acid or polyamine transport systems or through
      the choline-uptake system. In contrast, PQ efflux from cells is reported to be
      mediated by P-glycoprotein. Therefore, we evaluated PQ-induced cytotoxicity and
      the effect of some substrates/blockers of these transporters (such as arginine, L
      valine, putrescine, hemicholinium-3 and GF120918) on such cytotoxicity. RBE4
      cells were shown to be extremely resistant to PQ after 24 h of exposure; even at
      concentrations as high as 50 mM approximately 45% of the cells remained viable.
      Prolonging exposure until 48 h elicited significant cytotoxicity only for PQ
      concentrations above 5 mM. Although hemicholinium-3, a choline-uptake system
      inhibitor, significantly protected cells against PQ-induced toxicity, none of the
      effects were observed for arginine, L-valine or putrescine. Meanwhile, inhibiting
      the efflux pump P-glycoprotein using GF120918 significantly enhanced PQ-induced
      cytotoxicity. In conclusion, PQ used the choline-uptake system, instead of the
      transporters for the basic or neutral amino acids or for the polyamines, to enter
      RBE4 cells. P-glycoprotein extrudes PQ back to the extracellular medium. However,
      this efflux mechanism only partially explains the observed RBE4 resistance to PQ.

PMID- 24105844
TI  - Comparative evaluation of the diagnostic potential of recombinant envelope
      proteins and native cell culture purified viral antigens of Chikungunya virus.
AB  - Despite the fact that Chikungunya resurgence is associated with epidemic of
      unprecedented magnitude, there are challenges in the field of its clinical
      diagnosis. However, serological tests in an ELISA format provide a rapid tool for
      the diagnosis of Chikungunya infection. Indeed, ELISAs based on recombinant
      proteins hold a great promise as these methods are cost effective and are free
      from the risk of handling biohazardous material. In this study, the performance
      of recombinant CHIKV antigens was compared in various ELISA formats for the
      diagnosis of Chikungunya. Two recombinant antigens derived from the envelope
      proteins of Chikungunya virus were prepared and evaluated by comparing their
      competence for detecting circulating antibodies in serum samples of patients
      infected with CHIKV using MAC-ELISA and indirect IgM-ELISA. The efficacy of the
      recombinant antigens was also compared with the native antigen. The indirect
      antibody capture IgM microplate ELISA revealed >=90% concordance with the native
      antigen in detecting the CHIKV specific IgM antibodies whereas the recombinant
      antigen based MAC-ELISA showed 100% specificity. The recombinant antigens used in
      this study were effective and reliable targets for the diagnosis of CHIKV
      infection and also provide an alternative for native antigen use which is
      potentially biohazardous.

PMID- 24105846
TI  - Cationic, two-coordinate gold pi complexes.
AB  - Cationic, two-coordinate gold pi complexes that contain a phosphine or N
      heterocyclic supporting ligand have attracted considerable attention recently
      owing to the potential relevance of these species as intermediates in the gold
      catalyzed functionalization of C-C multiple bonds. Although neutral two
      coordinate gold pi complexes have been known for over 40 years, examples of the
      cationic two-coordinate gold(I) pi complexes germane to catalysis remained
      undocumented prior to 2006. This situation has changed dramatically in recent
      years and well-defined examples of two-coordinate, cationic gold pi complexes
      containing alkene, alkyne, diene, allene, and enol ether ligands have been
      documented. This Minireview highlights this recent work with a focus on the
      structure, bonding, and ligand exchange behavior of these complexes.

PMID- 24105848
TI  - Reduction in microparticle adsorption using a lateral interconnection method in a
      PDMS-based microfluidic device.
AB  - Microparticle adsorption on microchannel walls occurs frequently due to
      nonspecific interactions, decreasing operational performance in pressure-driven
      microfluidic systems. However, it is essential for delicate manipulation of
      microparticles or cells to maintain smooth fluid traffic. Here, we report a novel
      microparticle injection technique, which prevents particle loss, assisted by
      sample injection along the direction of fluid flow. Sample fluids, including
      microparticles, mammalian (U937), and green algae (Chlorella vulgaris) cells,
      were injected directly via a through hole drilled in the lateral direction,
      resulting in a significant reduction in microparticle attachment. For digital
      microfluidic application, the proposed regime achieved a twofold enhancement of
      single-cell encapsulation compared to the conventional encapsulation rate, based
      on a Poisson distribution, by reducing the number of empty droplets. This novel
      interconnection method can be straightforwardly integrated as a microparticle or
      cell injection component in integrated microfluidic systems. 

PMID- 24105847
TI  - Effect of novel fiber ingredients on ileal and total tract digestibility of
      energy and nutrients in semi-purified diets fed to growing pigs.
AB  - BACKGROUND: Consumption of different dietary fibers may influence the
      digestibility of carbohydrates and other nutrients. Therefore the objectives of
      this experiment were to determine the effect of novel fiber ingredients on the
      apparent ileal digestibility (AID) and apparent total tract digestibility (ATTD)
      of gross energy (GE), dry matter (DM), crude protein (CP) and total dietary fiber
      (TDF) in pigs and to calculate the standardized digestibility of analyzed TDF in
      four novel fiber ingredients. RESULTS: The AID of DM and GE in diets containing
      novel fiber ingredients was less (P < 0.05) than in a maltodextrin diet. Addition
      of cellulose or pullulan, but not resistant starch (RS) 60, RS 75 or soluble corn
      fiber 70, reduced (P < 0.05) the AID of CP. The average ileal and total tract
      endogenous losses of analyzed TDF were calculated at 25.25 and 42.87 g kg-1 DM
      intake, respectively. CONCLUSION: Addition of novel fiber ingredients to a
      maltodextrin-based diet had different effects on the AID of DM, CP, GE and TDF.
      Measurements of the standardized digestibility of analyzed TDF may be a better
      indicator of TDF fermentability than measurements of AID and ATTD of TDF, because
      some endogenous metabolites may be analyzed as TDF.

PMID- 24105849
TI  - Suppressing thermal conductivity of suspended tri-layer graphene by gold
      deposition.
AB  - A simple and general strategy for suppressing the thermal conductivity in
      graphene is shown. The strategy uses gold nano-particles physically deposited on
      graphene to continuously reduce the thermal conductivity of graphene with
      increasing coverage, which demonstrates the potential for practical development
      of graphene-based devices with tunable thermal conductivity for thermal
      management. 

PMID- 24105850
TI  - High throughput screening of natural products for anti-mitotic effects in MDA-MB
      231 human breast carcinoma cells.
AB  - Some of the most effective anti-mitotic microtubule-binding agents, such as
      paclitaxel (Taxus brevifolia) were originally discovered through robust National
      Cancer Institute botanical screenings. In this study, a high-through put
      microarray format was utilized to screen 897 aqueous extracts of commonly used
      natural products (0.00015-0.5 mg/mL) relative to paclitaxel for anti-mitotic
      effects (independent of toxicity) on proliferation of MDA-MB-231 cells. The data
      obtained showed that less than 1.34 % of the extracts tested showed inhibitory
      growth (IG50 ) properties <0.0183 mg/mL. The most potent anti-mitotics
      (independent of toxicity) were Mandrake root (Podophyllum peltatum), Truja twigs
      (Thuja occidentalis), Colorado desert mistletoe (Phoradendron flavescens), Tou Gu
      Cao [symbol: see text] Speranskia herb (Speranskia tuberculata), Bentonite clay,
      Bunge root (Pulsatilla chinensis), Brucea fruit (Brucea javanica), Madder root
      (Rubia tinctorum), Gallnut of Chinese Sumac (Melaphis chinensis), Elecampane root
      (Inula Helenium), Yuan Zhi [symbol: see text] root (Polygala tenuifolia), Pagoda
      Tree fruit (Melia Toosendan), Stone root (Collinsonia Canadensis), and others
      such as American Witchhazel, Arjun, and Bladderwrack. The strongest tumoricidal
      herbs identified from amongst the subset evaluated for anti-mitotic properties
      were wild yam (Dioscorea villosa), beth root (Trillium Pendulum), and alkanet
      root (Lithospermum canescens). Additional data was obtained on a lesser
      recognized herb: (S. tuberculata), which showed growth inhibition on BT-474
      (human ductal breast carcinoma) and Ishikawa (human endometrial adenocarcinoma)
      cells with ability to block replicative DNA synthesis, leading to G2 arrest in
      MDA-MB-231 cells. In conclusion, these findings present relative potency of anti
      mitotic natural plants that are effective against human breast carcinoma MDA-MB
      231 cell division.

PMID- 24105851
TI  - Subgroups of enlarged vestibular aqueduct in relation to SLC26A4 mutations and
      hearing loss.
AB  - OBJECTIVES/HYPOTHESIS: To investigate possible association of hearing loss and
      SLC26A4 mutations with the subgroups of enlarged vestibular aqueduct (EVA)
      morphology in Japanese subjects with hearing loss. STUDY DESIGN: Retrospective
      multicenter study. METHODS: Forty-seven subjects who had vestibular aqueduct with
      midpoint diameter >1 mm by computed tomography of the temporal bone were enrolled
      at multiple sites across Japan, and DNA samples and clinical data were collected.
      EVA morphology was classified into four subgroups by the pattern of enlargement:
      aperture, aperture and midpoint, midpoint, and borderline enlargement. Venous
      blood DNA samples were subjected to polymerase chain reaction-based direct
      sequencing of all exons and exon-intron boundaries of the SLC26A4. RESULTS: Four
      novel SLC26A4 mutations were identified in the present study. SLC26A4 mutations
      were detected in almost all subjects with aperture, aperture and midpoint, and
      midpoint enlargement. In contrast, 71% of subjects with borderline enlargement
      had no SLC26A4 mutation. No significant difference was found in the distribution
      of truncating and nontruncating SLC26A4 mutations between the EVA subgroups. In
      addition, no significant correlation was observed between the EVA subgroups and
      hearing levels, incidence of hearing fluctuation, or progression of hearing loss.
      CONCLUSIONS: Subgroups of EVA morphology were significantly correlated with the
      presence or absence of SLC26A4 mutation. In a subgroup analysis of subjects with
      SLC26A4 mutations, however, differences in the EVA subgroups were not correlated
      with SLC26A4 genotypes or characteristics of hearing loss. LEVEL OF EVIDENCE: NA.

PMID- 24105852
TI  - Anion-templated assembly and magnetocaloric properties of a nanoscale {Gd38} cage
      versus a {Gd48} barrel.
AB  - The comprehensive study reported herein provides compelling evidence that anion
      templates are the main driving force in the formation of two novel nanoscale
      lanthanide hydroxide clusters, {Gd38(ClO4)6} (1) and {Gd48Cl2(NO3)} (2),
      characterized by single-crystal X-ray crystallography, infrared spectroscopy, and
      magnetic measurements. {Gd38(ClO4)6}, encapsulating six ClO4(-) ions, features a
      cage core composed of twelve vertex-sharing {Gd4} tetrahedrons and one Gd???Gd
      pillar. When Cl(-) and NO3(-) were incorporated in the reaction instead of ClO4(
      ), {Gd48Cl2(NO3)} is obtained with a barrel shape constituted by twelve vertex
      sharing {Gd4} tetrahedrons and six {Gd5} pyramids. What is more, the cage-like
      {Gd38} can be dynamically converted into the barrel-shaped {Gd48} upon Cl(-) and
      NO3(-) stimulus. To our knowledge, it is the first time that the linear M-O-M'
      fashion and the unique MU8-ClO4(-) mode have been crystallized in pure lanthanide
      complex, and complex 2 represents the largest gadolinium cluster. Both of the
      complexes display large magnetocaloric effect in units of J kg(-1) K(-1) and mJ
      cm(-3) K(-1) on account of the weak antiferromagnetic exchange, the high
      N(Gd)/M(W) ratio (magnetic density), and the relatively compact crystal lattice
      (mass density).

PMID- 24105854
TI  - Six pyranoside forms of free 2-deoxy-D-ribose.

PMID- 24105853
TI  - Avian egg latebra as brain tissue water diffusion model.
AB  - PURPOSE: Simplified models of non-monoexponential diffusion signal decay are of
      great interest to study the basic constituents of complex diffusion behavior in
      tissues. The latebra, a unique structure uniformly present in the yolk of avian
      eggs, exhibits a non-monoexponential diffusion signal decay. This model is more
      complex than simple phantoms based on differences between water and lipid
      diffusion, but is also devoid of microscopic structures with preferential
      orientation or perfusion effects. METHODS: Diffusion scans with multiple b-values
      were performed on a clinical 3 Tesla system in raw and boiled chicken eggs
      equilibrated to room temperature. Diffusion encoding was applied over the ranges
      5-5,000 and 5-50,000 s/mm(2). A low read-out bandwidth and chemical shift was
      used for reliable lipid/water separation. Signal decays were fitted with
      exponential functions. RESULTS: The latebra, when measured over the 5-5,000
      s/mm(2) range, exhibited independent of preparation clearly biexponential
      diffusion, with diffusion parameters similar to those typically observed in in
      vivo human brain. For the range 5-50,000 s/mm(2), there was evidence of a small
      third, very slow diffusing water component. CONCLUSION: The latebra of the avian
      egg contains membrane structures, which may explain a deviation from a simple
      monoexponential diffusion signal decay, which is remarkably similar to the
      deviation observed in brain tissue.

PMID- 24105855
TI  - Blinded sample size re-estimation for recurrent event data with time trends.
AB  - The use of an internal pilot study for blinded sample size re-estimation (BSSR)
      allows to reduce uncertainty on the appropriate sample size compared with
      conventional fixed sample size designs. Recently BSSR procedures for recurrent
      event data were proposed and investigated. These approaches assume treatment
      specific constant event rates that might not always be appropriate as found in
      relapsing multiple sclerosis. On the basis of a proportional intensity frailty
      model, we propose methods for BSSR in situations where a time trend of the event
      rates is present. For the sample size planning and the final analysis standard
      negative binomial methods can be used, as long as the patient follow-up time is
      approximately equal in the treatment groups. To re-estimate the sample size at
      interim, however, a full likelihood analysis is necessary. Operating
      characteristics such as rejection probabilities and sample size distribution are
      evaluated in a simulation study motivated by a systematic review in relapsing
      multiple sclerosis. The key factors affecting the operating characteristics are
      the study duration and the length of the recruitment period. The proposed
      procedure for BSSR controls the type I error rate and maintains the desired power
      against misspecifications of the nuisance parameters.

PMID- 24105856
TI  - An international survey of pediatric apheresis practice.
AB  - INTRODUCTION: Pediatric apheresis (PA) has distinct characteristics compared to
      adult apheresis, and requires specialized knowledge and experience to perform
      safely, particularly in low-weight patients. As evidence-based medicine advances
      the field of therapeutic apheresis, increased attention must be paid to pediatric
      patients with conditions for which apheresis is indicated. METHODS: An electronic
      survey of >5,000 potential participants throughout the world was conducted to
      ascertain the scope and the current state of practice. RESULTS: The survey
      elicited 159 responses from 12 countries; 107 of the responses provided
      sufficient information for analysis. Participants performed an average of 176 PA
      procedures/year (range: 1-2,000). The types of PA procedures were therapeutic
      plasma exchange (92% of centers), red cell exchange (86%), leukocyte depletion
      (87%) and peripheral blood hematopoietic progenitor cell collection (72%). More
      than 65% of the centers had treated children older than 5 years with PA. Many
      centers had also performed PA on younger children; 40% have treated patients <12
      months of age; 61% had treated patients 1-5 years old. 36% of centers reported
      that they would perform apheresis regardless of patient weight; 18% used a 5 kg
      threshold, 11% used 5-10 kg, and 17% used 10 kg as their weight threshold.
      CONCLUSION: This report is the largest single survey of centers performing PA.
      The results provide information about the scope and diversity of PA and identify
      areas where considerable variability in practice exists. Further exploration of
      these differences could establish best practices in PA through international
      research and collaboration.

PMID- 24105857
TI  - Interactive behaviors of American Indian mothers and their premature infants.
AB  - The interactive behaviors of 17 American Indian mothers and their premature
      infants and selected maternal and infant factors affecting those behaviors were
      measured using naturalistic observation and the Home Observation for Measurement
      of the Environment (HOME) Inventory at 3, 6, and 12 months corrected infant age.
      The frequency of some maternal behaviors changed over the first 12 months.
      Mothers spent less time holding, looking at, touching, and interacting with their
      premature infants and more time uninvolved as the infant aged. Maternal education
      and infant illness severity were associated with mother-infant interactive
      behaviors and HOME Inventory scores. These findings emphasize the importance of
      maternal and infant factors affecting the interactions between American Indian
      premature infants and their mothers.

PMID- 24105858
TI  - Different patterns and development characteristics of processing written
      logographic characters and alphabetic words: an ALE meta-analysis.
AB  - The neural systems for phonological processing of written language have been well
      identified now, while models based on these neural systems are different for
      different language systems or age groups. Although each of such models is mostly
      concordant across different experiments, the results are sensitive to the
      experiment design and intersubject variability. Activation likelihood estimation
      (ALE) meta-analysis can quantitatively synthesize the data from multiple studies
      and minimize the interstudy or intersubject differences. In this study, we
      performed two ALE meta-analysis experiments: one was to examine the neural
      activation patterns of the phonological processing of two different types of
      written languages and the other was to examine the development characteristics of
      such neural activation patterns based on both alphabetic language and logographic
      language data. The results of our first meta-analysis experiment were consistent
      with the meta-analysis which was based on the studies published before 2005. And
      there were new findings in our second meta-analysis experiment, where both adults
      and children groups showed great activation in the left frontal lobe, the left
      superior/middle temporal gyrus, and the bilateral middle/superior occipital
      gyrus. However, the activation of the left middle/inferior frontal gyrus was
      found increase with the development, and the activation was found decrease in the
      following areas: the right claustrum and inferior frontal gyrus, the left
      inferior/medial frontal gyrus, the left middle/superior temporal gyrus, the right
      cerebellum, and the bilateral fusiform gyrus. It seems that adults involve more
      phonological areas, whereas children involve more orthographic areas and semantic
      areas.

PMID- 24105863
TI  - Internal repair of left ventricular pseudoaneurysm late after mitral valve
      replacement.
AB  - Late left ventricular pseudoaneurysm is a rare complication after mitral valve
      replacement. Most investigators have recommended surgical repair to treat left
      ventricular pseudoaneurysm, since untreated left ventricular pseudoaneurysm have
      a high risk of rupture. Here, we report a case of a 57-year old man with left
      ventricular pseudoaneurysm. He had two prior mitral valve replacements 16 and 19
      years ago, as well as mitral and aortic valve endocarditis causing mitral valve
      perivalvular leak and perforation of the aortic valve. The mitral and aortic
      valves were replaced with bovine pericardial valves. Left ventricular
      pseudoaneurysm was successfully repaired internally in our case because the
      internal wall at the level of the left ventricle was very fibrotic and matured. 

PMID- 24105864
TI  - Evaluation of calcium loss after transcatheter aortic valve implantation.
AB  - OBJECTIVES: Aortic valve calcification and changes after transcatheter aortic
      valve implantation (TAVI) were specifically assessed by computed tomography (CT).
      The main difference between TAVI and the conventional technique is the
      compression of the cusps of the calcified native valve against the aortic wall
      before implantation. The objective of this study was to quantify the segmented
      calcification in the area of the basal annular plane before and after TAVI.
      METHODS: The CT scans of 20 patients (13 male and 7 female; mean age: 82.9 +/-
      8.1 years) were assessed. The aortic valve calcification was segmented; derived
      from this segmentation volume, mass and Hounsfield units (HU)/density of the
      calcifications on the annulus and cusps before and after TAVI were evaluated. Pre
      and postoperative data were compared regarding potential calcification loss and
      calcification distances to the left and right coronary ostia. RESULTS:
      Significantly lower postprocedural mean volumes and masses for all cusps (P <
      0.001) were found. The mean differences in the volume for the non-coronary, right
      coronary and left-coronary cusp were -156.8 +/- 53.73, -155.5 +/- 62.54 and -115
      +/- 57.53 mm(3), respectively, and differences in mass were -88.78 +/- 29.48, 
      95.2 +/- 39.27 and -71.56 +/- 35.62 mg, respectively. Over all cusps, mean HU
      increased after intervention [784.41 +/- 92.5 HU (pre) and 818.63 +/- 78.71 HU
      (post); P < 0.004]. In 80.03% of all cusps, calcification loss was found; all
      patients were affected. Significantly lower (P < 0.047) postprocedural mean
      distances were found from the left and right coronary ostia to the next
      calcification point. CONCLUSIONS: Our results show a significant loss of
      calcification in all patients after TAVI, with a reduction in the calcification
      distances to the coronary ostia and the compression of calcification in the area
      of the device landing zone. The clinical implications of this finding need to be
      investigated further.

PMID- 24105865
TI  - Left ventricular mass regression after sutureless implantation of the Perceval S
      aortic valve bioprosthesis: preliminary results.
AB  - OBJECTIVES: Left ventricular (LV) hypertrophy in aortic stenosis (AS) is
      considered a compensatory response helping maintain systolic function, but
      constitutes a risk factor for cardiac morbidity and mortality. The aim of this
      study was to assess the degree of LV mass regression after sutureless
      implantation of the Perceval S aortic valve bioprosthesis (Sorin Group, Saluggia,
      Italy). METHODS: Between March 2010 and July 2012, 78 patients with symptomatic
      AS underwent isolated aortic valve replacement (AVR) with the Perceval
      bioprosthesis. Mean age was 77.1 +/- 5.3 years, 46 patients were female (59%) and
      mean logistic EuroSCORE was 11 +/- 7.5%. Echocardiography was performed
      preoperatively, at discharge, and at follow-up (mean 13.5 +/- 7.3 months). LV
      mass was calculated using the Devereux formula and indexed to body surface area.
      RESULTS: There was 1 in-hospital non-cardiac death and 3 late deaths. LV mass
      index decreased from 148.4 +/- 46 g/m(2) at baseline to 119.7 +/- 38.5 g/m(2) at
      follow-up (P = 0.002). No significant changes were observed in LV hypertrophy
      and/or relative wall thickness >0.42 as well as in LV ejection fraction. Mean
      aortic gradient decreased from 49.5 +/- 15.8 mmHg at baseline to 11.6 +/- 5.1
      mmHg at discharge and 8.3 +/- 4.4 mmHg at follow-up (P < 0.001), resulting in
      significant clinical improvement. No moderate or severe paravalvular leakage was
      observed at discharge and at follow-up. CONCLUSIONS: In AS patients, isolated AVR
      with the Perceval sutureless bioprosthesis is associated with significant LV mass
      regression at 1-year follow-up. However, longer-term follow-up is necessary to
      confirm these findings.

PMID- 24105866
TI  - Conversion of phenols into selenophenols: seleno Newman-Kwart rearrangement.
AB  - A 'Se'lling point: The first thermally induced OAr ->SeAr migration reaction is
      reported, and it can be used to prepare aryl selenols in three steps from the
      corresponding phenols. O-aryl selenocarbamates rearrange to Se-aryl carbamates
      via a four-membered transition state. The aryl selenols (isolated as the
      diselenides) can be prepared by hydrolysis of the Se-aryl selenocarbamates. 

PMID- 24105867
TI  - Alteration in cellular viability, pro-inflammatory cytokines and nitric oxide
      production in nephrotoxicity generation by Amphotericin B: involvement of PKA
      pathway signaling.
AB  - Amphotericin B is one of the most effective antifungal agents; however, its use
      is often limited owing to adverse effects, especially nephrotoxicity. The purpose
      of this study was to evaluate the effect of inhibiting the PKA signaling pathway
      in nephrotoxicity using Amphotericin B from the assessment of cell viability, pro
      inflammatory cytokines and nitric oxide (NO) production in LLC-PK1 and MDCK cell
      lines. Amphotericin B proved to be cytotoxic for both cell lines, as assessed by
      the mitochondrial enzyme activity (MTT) assay; caused DNA fragmentation,
      determined by flow cytometry using the propidium iodide (PI) dye; and activated
      the PKA pathway (western blot assay). In MDCK cells, the inhibition of the PKA
      signaling pathway (using the H89 inhibitor) caused a significant reduction in DNA
      fragmentation. In both cells lines the production of interleukin-6 (IL)-6 proved
      to be a dependent PKA pathway, whereas tumor necrosis factor-alpha (TNF-alpha)
      was not influenced by the inhibition of the PKA pathway. The NO production was
      increased when cells were pre-incubated with H89 followed by Amphotericin B, and
      this production produced a dependent PKA pathway in LLC-PK1 and MDCK cells lines.
      Therefore, considering the present study's results as a whole, it can be
      concluded that the inhibition of the PKA signaling pathway can aid in reducing
      the degree of nephrotoxicity caused by Amphotericin B.

PMID- 24105868
TI  - Fast evaluation of enantioselective drug metabolism by electrophoretically
      mediated microanalysis: application to fluoxetine metabolism by CYP2D6.
AB  - In this work, a capillary electrophoretic methodology for the enantioselective in
      vitro evaluation of drugs metabolism is applied to the evaluation of fluoxetine
      (FLX) metabolism by cytochrome 2D6 (CYP2D6). This methodology comprises the in
      capillary enzymatic reaction and the chiral separation of FLX and its major
      metabolite, norfluoxetine enantiomers employing highly sulfated beta-CD and the
      partial filling technique. The methodology employed in this work is a fast way to
      obtain a first approach of the enantioselective in vitro metabolism of racemic
      drugs, with the additional advantage of an extremely low consumption of enzymes,
      CDs and all the reagents involved in the process. Michaelis-Menten kinetic
      parameters (Km and Vmax ) for the metabolism of FLX enantiomers by CYP2D6 have
      been estimated by nonlinear fitting of experimental data to the Michaelis-Menten
      equation. Km values have been found to be 30 +/- 3 MUM for S-FLX and 39 +/- 5 MUM
      for R-FLX. Vmax estimations were 28.6 +/- 1.2 and 34 +/- 2 pmol.min(-1) .(pmol
      CYP)(-1) for S- and R-FLX, respectively. Similar results were obtained using a
      single enantiomer (R-FLX), indicating that the use of the racemate is a good
      option for obtaining enantioselective estimations. The results obtained show a
      slight enantioselectivity in favor of R-FLX. 

PMID- 24105869
TI  - ATP-binding cassette transporters in liver.
AB  - The human ATP-binding cassette (ABC) superfamily consists of 48 members with 14
      of them identified in normal human liver at the protein level. Most of the ABC
      members act as ATP dependent efflux transport systems. In the liver, ABC
      transporters are involved in diverse physiological processes including export of
      cholesterol, bile salts, and metabolic endproducts. Consequently, impaired ABC
      transporter function is involved in inherited diseases like sitosterolemia,
      hyperbilirubinemia, or cholestasis. Furthermore, altered expression of some of
      the hepatic ABCs have been associated with primary liver tumors. This review
      gives a short overview about the function of hepatic ABCs. Special focus is
      addressed on the localization and ontogenesis of ABC transporters in the human
      liver. In addition, their expression pattern in primary liver tumors is
      discussed.

PMID- 24105870
TI  - Race-based job discrimination, disparities in job control, and their joint
      effects on health.
AB  - OBJECTIVES: To examine disparities between job control scores in Black and White
      subjects and attempt to discern whether self-rated low job control in Blacks may
      arise from structural segregation into different jobs, or represents individual
      responses to race-based discrimination in hiring or promotion. METHODS: Data from
      the National Survey of Midlife in the United States (MIDUS) were analyzed by
      mixed-effects linear regression and variance regression to determine the effects
      of grouping by occupation, and racial discrimination in hiring or promotion, on
      control scores from the Job Content Questionnaire in Black and White subjects.
      Path analyses were constructed to determine the mediating effect of
      discrimination on pathways from education and job control to self-rated health.
      RESULTS: Black subjects exhibited lower mean job control scores compared to
      Whites (mean score difference 2.26, P < 0.001) adjusted for age, sex, education,
      and income. This difference narrowed to 1.86 when adjusted for clustering by
      occupation, and was greatly reduced by conditioning on race-based discrimination
      (score difference 1.03, P = 0.12). Path analyses showed greater reported
      discrimination in Blacks with increasing education, and a stronger effect of job
      control on health in Black subjects. CONCLUSIONS: Individual racially-based
      discrimination appears a stronger determinant than structural segregation in
      reduced job control in Black workers, and may contribute to health disparities
      consequent on work.

PMID- 24105871
TI  - New approach to assess bioequivalence parameters using generalized gamma mixed
      effect model (model-based asymptotic bioequivalence test).
AB  - In the pharmacokinetic (PK) study under a 2x2 crossover design that involves both
      the test and reference drugs, we propose a mixed-effects model for the drug
      concentration-time profiles obtained from subjects who receive different drugs at
      different periods. In the proposed model, the drug concentrations repeatedly
      measured from the same subject at different time points are distributed according
      to a multivariate generalized gamma distribution, and the drug concentration-time
      profiles are described by a compartmental PK model with between-subject and
      within-subject variations. We then suggest a bioequivalence test based on the
      estimated bioavailability parameters in the proposed mixed-effects model. The
      results of a Monte Carlo study further show that the proposed model-based
      bioequivalence test is not only better on maintaining its level but also more
      powerful for detecting the bioequivalence of the two drugs than the conventional
      bioequivalence test based on a non-compartmental analysis or the one based on a
      mixed-effects model with a normal error variable. The application of the proposed
      model and test is finally illustrated by using data sets in two PK studies.

PMID- 24105872
TI  - Air-stable n-channel organic single crystal field-effect transistors based on
      microribbons of core-chlorinated naphthalene diimide.
AB  - Ribbon-shaped single crystal transistors based on naphthalene diimide Cl2-NDI
      exhibit excellent n-channel performance with the mobility as high as 8.6 cm(2) V(
      1) s(-1) in air. The combination of ambient stability and high mobility n-channel
      transport closes the gap between p- and n-channel SCFETs and opens the door for
      the manufacture of high performance complementary organic circuits.

PMID- 24105873
TI  - Surgery for pediatric invasive fungal sinonasal disease.
AB  - OBJECTIVES/HYPOTHESIS: To evaluate the management and outcomes of children with
      invasive fungal sinonasal disease treated with radical surgery. STUDY DESIGN:
      Retrospective case series. METHODS: From 1994 to 2007, 11 pediatric patients were
      identified with invasive fungal sinonasal disease treated surgically by the same
      pediatric otolaryngologist. Collected data included demographics, oncologic
      diagnoses, absolute neutrophil counts, symptoms, computed tomography scan
      findings, biopsy and culture results, surgical procedures, concurrent medical
      therapies, complications, and survival. RESULTS: The studied patient population
      consisted of four males and seven females with an average age of 10 years (range,
      2-14 years). Six patients were diagnosed with acute lymphoblastic leukemia and
      five with acute myeloid leukemia, which included 10 cases of relapsed disease.
      The average number of severely neutropenic days prior to diagnosis of an invasive
      fungal infection was 18 (range, 8-41 days). Culture results demonstrated
      Alternaria in seven patients and Aspergillus in four. Nine patients underwent an
      external medial maxillectomy, five of which were bilateral, and six underwent
      septectomy. All 11 patients (100%) were cured of their invasive fungal sinonasal
      disease without relapse. Three patients eventually died from unrelated causes.
      CONCLUSIONS: Invasive fungal sinonasal disease is a life-threatening problem in
      immunocompromised children, especially with relapsed leukemia. Successful
      treatment depends on timely and aggressive surgical, antifungal, and supportive
      therapies. To our knowledge, this study represents the largest series of
      pediatric patients with invasive fungal sinonasal disease managed via an
      aggressive surgical approach with the best outcomes to date. LEVEL OF EVIDENCE:
      4.

PMID- 24105874
TI  - Thiepin-fused heteroacenes: simple synthesis, unusual structure, and
      semiconductors with less anisotropic behavior.
AB  - The simple one-pot syntheses of sulfur-rich thiepin-fused heteroacences with an
      alkylidene-fluorene framework, THA1 and THA6 (thiepin-fused heteroacene 1 or 6,
      in which the thiepin is conjugated at both ortho positions with S?CH3 or S?C6 H13
      , respectively), is reported. Based on electrochemical studies and theoretical
      calculations, their LUMO energies are relatively low (-3.26 eV), and their HOMO
      and HOMO-1 orbitals are nearly degenerate. The thiepin ring contributes mainly to
      HOMO-1 and LUMO orbitals, however, HOMO orbitals dominantly reside on
      thienoacence rings. Within the crystal of THA1, the molecules adopt a herringbone
      arrangement and multiple intermolecular interactions lead to the formation of a
      2D network. Interestingly, THA6 shows totally different intermolecular
      arrangements. Organic field-effect transistor (OFET) devices show both compounds
      exhibiting p-type semiconducting behavior. Thin films or microcrystals of THA1
      possess relatively high hole mobility. Moreover, the mobilities of the
      microcrystal of THA1 along three directions are in the same order, thus the hole
      carrier transporting within the hexagonal-plane of microcrystal of THA1 exhibits
      less anisotropic behavior. In comparison, both thin films and microrods of THA6
      show low hole mobilities. This agrees well with the intermolecular arrangements
      and interactions within crystal of THA6. Further theoretical calculations reveal
      that significant intermolecular electronic coupling among HOMO-1 orbitals and
      sulfur atoms play an important role in intermolecular electronic coupling for
      THA1. 

PMID- 24105875
TI  - Dendritic remodeling in the adolescent medial prefrontal cortex and the
      basolateral amygdala of male and female rats.
AB  - There is recent evidence of continuing development throughout adolescence in two
      neural areas involved in emotion and cognition, the basolateral amygdala (BLN)
      and the medial prefrontal cortex (mPFC). Previous research from our laboratory
      has demonstrated a cellular loss in both of these brain regions in rats between
      postnatal day (P) 35 and 90. This study investigates dendritic changes in
      pyramidal neurons of the BLN and Layer 5 of the mPFC at P20 (juvenile), 35
      (puberty), and 90 (adulthood) in hooded rats of both sexes. Dendritic branching
      and dendritic spines were quantified in Golgi-Cox impregnated tissue. Between P20
      and 35, dendritic length and complexity, as well as the density of dendritic
      spines, increased in both structures. Between P35 and 90, dendritic spines in the
      mPFC neurons significantly decreased in both sexes, while a loss of basilar
      dendrites was only detected in females. In the BLN, there was an increase in the
      number of branches between P35 and 90 without an increase in the total length of
      the dendritic tree. BLN spine density also remained stable during this period.
      These results show that the dendritic tree grows prior to puberty while dendritic
      remodeling and pruning occurs after puberty in both of these neural areas. This
      late development may lead to susceptibilities to psychopathologies and addictions
      that often develop at this time.

PMID- 24105876
TI  - Influence of two hop (Humulus lupulus L.) varieties on in vitro dry matter and
      crude protein degradability and digestibility in ruminants.
AB  - BACKGROUND: Hop cones contain several antimicrobial substances. The aim of the
      study was to determine the effects of two hop varieties, Aurora and Dana, on
      substrate (diet for a dairy cow, producing 30 kg milk daily) in vitro dry matter
      (DM) and crude protein (CP) degradability and digestibility. RESULTS: In the in
      vitro trial freshly ground hops were added to the buffered rumen fluid in
      concentrations simulating the cow's daily intake of 50, 100 and 200 g of hops.
      Increasing the concentration of hops decreased (P < 0.05) both the average in
      vitro DM degradabilities of substrate from 725 to 592, 553 and 481 g kg(-1),
      respectively, and in vitro CP degradabilities of substrate from 752 to 566, 561
      and 478 g kg(-1), respectively. The reduction of in vitro DM and CP degradability
      is counterbalanced by the (invariable) in vitro DM and CP digestibility. The
      difference between CP digestibility and degradability represents an estimate of
      the amount of rumen 'bypass' protein which increased with increasing
      concentration of hops from 172 to 454 g kg(-1). CONCLUSIONS: Decreased DM and CP
      degradability and increased amount of rumen 'bypass' protein could lower the
      amounts of protein required by high-producing ruminant animals. However, this
      supposition needs a validation with in vivo trials.

PMID- 24105877
TI  - Morphology of the proboscis of Hubrechtella Juliae (Nemertea, Pilidiophora):
      implications for pilidiophoran monophyly.
AB  - The proboscis of Hubrechtella juliae was examined using transmission electron
      microscopy, scanning electron microscopy, and confocal laser scanning microscopy
      to reveal more features of basal pilidiophoran nemerteans for morphological and
      phylogenetic analysis. The proboscis glandular epithelium consists of sensory
      cells and four types of gland cells (granular, bacillary, mucoid, and
      pseudocnidae-containing cells) that are not associated with any glandular
      systems; rod-shaped pseudocnidae are 15-25 MUm in length; the central cilium of
      the sensory cells is enclosed by two rings of microvilli. The nervous plexus lies
      in the basal part of glandular epithelium and includes 26-33 (11-12 in juvenile)
      irregularly anastomosing nerve trunks. The proboscis musculature includes four
      layers: endothelial circular, inner diagonal, longitudinal, and outer diagonal;
      inner and outer diagonal muscles consist of noncrossing fibers; in juvenile
      specimen, the proboscis longitudinal musculature is divided into 7-8 bands. The
      endothelium consists of apically situated support cells with rudimentary cilia
      and subapical myocytes. Unique features of Hubrechtella's proboscis include:
      acentric filaments of the pseudocnidae; absence of tonofilament-containing
      support cells; two rings of microvilli around the central cilium of sensory
      cells; the occurrence of subendothelial diagonal muscles and the lack of an outer
      diagonal musculature (both states were known only in Baseodiscus species). The
      significance of these characters for nemertean taxonomy and phylogeny is
      discussed. The proboscis musculature in H. juliae and most heteronemerteans is
      bilaterally arranged, which can be considered a possible synapomorphy of
      Hubrechtellidae + Heteronemertea (= Pilidiophora).

PMID- 24105878
TI  - Have we given up on intra-aortic balloon counterpulsation in post-myocardial
      infarction cardiogenic shock?
AB  - The recently published Intra-aortic Balloon Pump in Cardiogenic Shock II (IABP
      SHOCK II) trial concluded that intra-aortic counterpulsation (IACP) does not
      reduce 30-day mortality in patients with cardiogenic shock (CS) complicating
      acute myocardial infarction (AMI) for whom early revascularization strategy was
      planned. The study resulted in downgrading IACP in post-AMI CS patients by
      certain professional organizations like the European Society of Cardiology.
      Although this is the largest and most important CS study of this decade, it
      suffers from considerable shortcomings: (1) time intervals from chest-pain onset
      or AMI recognition to revascularization, enrollment, and IACP initiation are not
      disclosed; (2) 86.6% of the treatment arm initiated IACP only post-percutaneous
      coronary intervention (PCI), and 4.3 % did not receive IACP at all; (3) 17.4% of
      the control arm crossed over to IACP or other mechanical support, mostly due to
      protocol violations; (4) there is no adjudication of the mortality events; (5)
      follow-up is limited to 30 days; and (5) both methodology (especially IACP device
      size) and quality of IACP are not evaluated and documented. Because the study
      assessed mostly the efficacy and safety of IACP initiated post-PCI, the study
      conclusions should not be extrapolated to IACP pre-PCI or during PCI in CS.
      Moreover, IACP had a favorable effect on the mortality of younger patients. Intra
      aortic counterpulsation should remain the first line of mechanical circulatory
      support for the hemodynamically compromised AMI patients with or without CS who
      are undergoing primary PCI. Early upgrade to more advanced mechanical circulatory
      support should be considered for selective suitable candidates who remain in
      refractory CS despite revascularization and IACP. 

PMID- 24105879
TI  - Development of quality indicators for women with urinary incontinence.
AB  - AIMS: To develop a means to measure the quality of care provided to women treated
      for urinary incontinence (UI) through the development of quality-of-care
      indicators (QIs). METHODS: We performed an extensive literature review to develop
      a set of potential quality indicators for the management of UI. QIs were modeled
      after those previously described in the Assessing the Care of Vulnerable Elders
      (ACOVE) project. Nine experts ranked the indicators on a nine-point scale for
      both validity and feasibility. We analyzed preliminary rankings of each indicator
      using the RAND Appropriateness Method. A forum was then held in which each
      indicator was thoroughly discussed by the panelists as a group, after which the
      indicators were rated a second time individually using the same nine-point scale.
      RESULTS: QIs were developed that addressed screening, diagnosis, work-up, and
      both non-surgical and surgical management. Areas of controversy included whether
      routine screening for incontinence should be performed, whether urodynamics
      should be performed before non-surgical management is initiated, and whether
      cystoscopy should be part of the pre-operative work-up of uncomplicated stress
      incontinence. Following the expert panel discussion, 27 of 40 potential
      indicators were determined to be valid for UI with a median score of at least
      seven on a nine-point scale. CONCLUSIONS: We identified 27 quality indicators for
      the care of women with UI. Once these QIs are pilot-tested for feasibility, they
      will be applied on a larger scale to measure the quality of care provided to
      women with UI in the United States.

PMID- 24105880
TI  - The effects of artemisinin on the proliferation and apoptosis of vascular smooth
      muscle cells of rats.
AB  - OBJECTIVE: The aim of this study was to evaluate the effect of artemisinin on the
      proliferation and apoptosis of rat vascular smooth muscle cells (VSMCs). METHOD:
      Primary rat VSMCs were treated with various doses of artemisinin. Cell
      proliferation was evaluated by 3-(4,5-dimethylthiazol-2-yl)-2,5
      diphenyltetrazolium bromide assay, and the messenger RNA and protein expressions
      of proliferating cell nuclear antigen were determined by reverse-transcription
      polymerase chain reaction and immunohistochemistry. Apoptosis was measured using
      annexin V and propidium iodide double staining evaluated by flow cytometry.
      Protein expression of Bax, Bcl2, and cyclin-dependent kinase 4 was determined by
      Western blot. RESULTS: After 72 h of treatment, artemisinin significantly
      inhibited VSMC proliferation in a dose-dependent manner. Treatment with 1 mM
      artemisinin for 72 h significantly reduced the expression of proliferating cell
      nuclear antigen messenger RNA. On the other hand, the same treatment increased
      the apoptosis of VSMCs, the activation of caspase-3, the Bax protein expression,
      and the Bax/Bcl2 ratio. CONCLUSION: The results suggest that artemisinin can
      effectively inhibit VSMC proliferation and induce VSMC apoptosis.

PMID- 24105881
TI  - Transition-metal-catalyzed laboratory-scale carbon-carbon bond-forming reactions
      of ethylene.
AB  - Ethylene, the simplest alkene, is the most abundantly synthesized organic
      molecule by volume. It is readily incorporated into transition-metal-catalyzed
      carbon-carbon bond-forming reactions through migratory insertions into alkylmetal
      intermediates. Because of its D2h symmetry, only one insertion outcome is
      possible. This limits byproduct formation and greatly simplifies analysis. As
      described within this Minireview, many carbon-carbon bond-forming reactions
      incorporate a molecule (or more) of ethylene at ambient pressure and temperature.
      In many cases, a useful substituted alkene is incorporated into the product. 

PMID- 24105882
TI  - Assessment of occupational health and safety hazard exposures among working
      college students.
AB  - BACKGROUND: Adolescents and young adults have higher injury rates than their
      adult counterparts in similar jobs. This study used the working college student
      population to assess health and safety hazards in the workplace, characterize
      related occupational diseases and injuries, and describe worker health/safety
      activities provided by employers. METHODS: College students (>=17 years old) were
      assessed via online surveys about work history, workplace exposure to hazards,
      occupational diseases/injuries, and workplace health/safety activities. RESULTS:
      Approximately half (51%) of participants (n = 1,147) were currently employed at
      the time of the survey or had been employed while enrolled in college.
      Restaurants (other than fast food) were the most frequently reported work
      setting. The most reported workplace hazards included noise exposure and contact
      with hot liquids/surfaces. Twenty percent of working students experienced injury
      at work; some injuries were severe enough to limit students' normal activities
      for >3 days (30%) or require medical attention (44%). Men had significantly
      higher prevalence of injuries (P = 0.05) and near-misses (P < 0.01) at work than
      women. Injury occurrence was associated with near-misses (AOR = 5.08, P < 0.01)
      and co-worker injuries (AOR = 3.19, P < 0.01) after gender and age adjustments.
      Most (77%) received worker safety training and half were given personal
      protective equipment (PPE) by their employers. CONCLUSIONS: Risk reduction from
      workplace injuries and illnesses among working college students may be achieved
      by implementing occupational health and safety (OHS) strategies including
      incorporation of OHS in the college curriculum, promotion of OHS by
      university/college student health services, and improving awareness of OHS online
      resources among college students, employers, and educators.

PMID- 24105883
TI  - Alterations in human muscle protein metabolism with aging: Protein and exercise
      as countermeasures to offset sarcopenia.
AB  - Aging is associated with a reduction in skeletal muscle mass-sarcopenia-the
      etiology of which is multifactorial. One mechanism is that aging has, as one of
      its hallmarks, a reduced sensitivity of skeletal muscle to the normally potent
      anabolic effects of protein feeding and resistance exercise, and to the
      anticatabolic effects of insulin, the combination of which has been termed
      "anabolic resistance." However, this reduced sensitivity of skeletal muscle to
      anabolic stimuli may, in some cases, be overcome by providing a greater quantity
      of the nutrition and/or exercise stimulus. Daily habitual physical activity
      appears to be a primary determinant of anabolic resistance as we have recently
      shown that as little as 14 days of reduced ambulatory activity was sufficient to
      induce anabolic resistance in the elderly by attenuating the postprandial
      increase in muscle protein synthesis (MPS). The etiology of anabolic resistance
      is complex and may include alterations in amino acid uptake/utilization, cell
      signaling status, muscle blood flow, and microvascular perfusion (impacting amino
      acid delivery and availability). Further, there appears to be sexual dimorphism
      with advancing age in the response of MPS to amino acid/insulin provision.
      Maintenance of physical activity during aging is of fundamental importance for
      skeletal muscle to allow it to appropriately respond to the anabolic effects of
      nutrition.

PMID- 24105884
TI  - Spatial encoding using the nonlinear field perturbations from magnetic materials.
AB  - PURPOSE: A proof-of-concept study was performed to assess the technical
      feasibility of using magnetic materials to generate spatial encoding fields.
      THEORY AND METHODS: Spatially varying magnetic fields were generated by the
      placement of markers with different volume susceptibilities within the imaging
      volume. No linear gradients were used for spatial encoding during the signal
      acquisition. A signal-encoding model is described for reconstructing the images
      encoded with these field perturbations. Simulation and proof-of-concept
      experimental results are presented. Experiments were performed using field
      perturbations from a cylindrical marker as an example of the new encoding fields.
      Based on this experimental setup, annular rings were reconstructed from signals
      encoded with the new fields. RESULTS: Simulation results were presented for
      different acquisition parameters. Proof-of-concept was supported by the
      correspondence of regions in an image reconstructed from experimental data
      compared to those in a conventional gradient-echo image. Experimental results
      showed that inclusions of dimensions 1.5 mm in size could be resolved with the
      experimental setup. CONCLUSION: This study shows the technical feasibility of
      using magnetic markers to produce encoding fields. Magnetic materials will allow
      generating spatial encoding fields, which can be tailored to an imaging
      application with less complexity and at lower cost compared to the use of
      gradient inserts.

PMID- 24105885
TI  - Fluorescent staining of protein in sodium dodecyl sulfate polyacrylamide gels by
      salicylaldehyde azine.
AB  - As a non-covalent fluorescence probe, in this study, salicylaldehyde azine (SA)
      was introduced as a sensitive fluorescence-based dye for detecting proteins both
      in 1-D and 2-D polyacrylamide electrophoresis gels. Down to 0.2 ng of single
      protein band could be detected within 1 h, which similars to that of
      glutaraldehyde (GA)-silver stain, but approximately four times higher than that
      of SYPRO Ruby fluorescent stain. Furthermore, comparative analysis of the MS
      compatibility of SA stain with SYPRO Ruby stain indicated that SA stain is
      compatible with the downstream of protein identification by liquid chromatography
      tandem mass spectrometry (LC-MS/MS). Additionally, the probable mechanism of the
      SA stain was investigated by molecular docking. The results demonstrated that the
      interaction between SA and protein was mainly contributed by hydrogen bonding and
      hydrophobic forces.

PMID- 24105886
TI  - Catalytic enantioselective synthesis of tertiary thiols from 5H-thiazol-4-ones
      and nitroolefins: bifunctional ureidopeptide-based Bronsted base catalysis.

PMID- 24105887
TI  - Fully inkjet-printed organic photodetectors with high quantum yield.
AB  - Bulk-heterojunction based organic photodetectors are fabricated by means of drop
      on-demand inkjet printing with vertical topology, inverted structure, and small
      footprint (about 100 MUm x 100 MUm). Due to optimization of the deposition
      technique, an external quantum efficiency in excess of 80% at 525 nm and a -3dB
      bandwidth of a few tens of kHz is achieved. 

PMID- 24105888
TI  - Life-stage-, sex-, and dose-dependent dietary toxicokinetics and relationship to
      toxicity of 2,4-dichlorophenoxyacetic acid (2,4-D) in rats: implications for
      toxicity test dose selection, design, and interpretation.
AB  - Life-stage-dependent toxicity and dose-dependent toxicokinetics (TK) were
      evaluated in Sprague Dawley rats following dietary exposure to 2,4
      dichlorophenoxyacetic acid (2,4-D). 2,4-D renal clearance is impacted by dose
      dependent saturation of the renal organic anion transporter; thus, this study
      focused on identifying inflection points of onset of dietary nonlinear TK to
      inform dose selection decisions for toxicity studies. Male and female rats were
      fed 2,4-D-fortified diets at doses to 1600 ppm for 4-weeks premating, <2 weeks
      during mating, and to test day (TD) 71 to parental (P1) males and to P1 females
      through gestation/lactation to TD 96. F1 offspring were exposed via milk with
      continuing diet exposure until postnatal day (PND) 35. As assessed by plasma area
      under the curve for the time-course plasma concentration, nonlinear TK was
      observed >= 1200 ppm (63 mg/kg/day) for P1 males and between 200 and 400 ppm (14
      27 mg/kg/day) for P1 females. Dam milk and pup plasma levels were higher on
      lactation day (LD) 14 than LD 4. Relative to P1 adults, 2,4-D levels were higher
      in dams during late gestation/lactation and postweaning pups (PND 21-35) and
      coincided with elevated intake of diet/kg body weight. Using conventional maximum
      tolerated dose (MTD) criteria based on body weight changes for dose selection
      would have resulted in excessive top doses approximately 2-fold higher than those
      identified incorporating critical TK data. These data indicate that demonstration
      of nonlinear TK, if present at dose levels substantially above real-world human
      exposures, is a key dose selection consideration for improving the human
      relevance of toxicity studies compared with studies employing conventional MTD
      dose selection strategies.

PMID- 24105889
TI  - Brainstem structures are primarily affected in an experimental model of severe
      scorpion envenomation.
AB  - Severe scorpion envenoming (SSE) is more frequent in children and is
      characterized by systemic dysfunctions with a mortality rate of up to 9%. Recent
      evidence shows that the central nervous system (CNS) plays a key role in
      triggering the cascade of symptoms present in SSE. The age-dependent role of the
      CNS in SSE lethality may be summarized in 3 hypotheses: (1) the shown increased
      blood brain barrier permeability of infants to the toxins would especially and
      primarily compromise neurovegetative control areas, (2) the neurons within these
      areas have high affinity to the toxins, and (3) the neurovascular interaction is
      such that SSE metabolically compromises proper function of toxin-targeted areas.
      A pharmacological magnetic resonance imaging paradigm was used to evaluate
      localized hemodynamic changes in relative cerebral blood volume (rCBV) for 30 min
      after the injection of TsTX, the most lethal toxin from the venom of the Tityus
      serrulatus scorpion. The brainstem showed significant rCBV reduction 1 min after
      TsTX administration, whereas rostral brain areas had delayed increase in rCBV
      (confirmed by laser Doppler measurements of cortical cerebral blood flow).
      Moreover, metabolic activity by 14C-2-deoxyglucose autoradiography showed the
      highest relative increase at the brainstem. To test whether TsTX has high
      affinity to brainstem neurons, the lateral ventricle was injected with Alexa
      Fluor 568 TsTX. Although some neurons showed intense fluorescence, the labeling
      pattern suggests that specific neurons were targeted. Altogether, these results
      suggest that brainstem areas involved in neurovegetative control are most likely
      within the primary structures triggering the cascade of symptoms present in SSE.

PMID- 24105890
TI  - Bioassay-directed fractionation and sub-fractionation for mutagenicity and
      chemical analysis of diesel exhaust particles.
AB  - Several types of diesel exhaust particles (DEPs) have been used for toxicology
      studies, including a high-organic automobile DEP (A-DEP) from Japan, and a low
      organic forklift DEP developed by the National Institute of Standards and
      Technology (N-DEP). However, these DEPs were not characterized extensively for
      chemical composition or sub-fractionated and tested extensively for mutagenicity.
      We collected a compressor-generated DEP (C-DEP) and characterized it by
      conducting bioassay-directed fractionation of the extractable organics in
      Salmonella and correlating the results by hierarchical clustering with the
      concentrations of 32 polycyclic aromatic hydrocarbons (PAHs). Relative to A- and
      N-DEP, the mutagenic potency of C-DEP was intermediate in TA100 +S9 (PAH
      mutagenicity) but was lowest in TA98 -S9 (nitroarene mutagenicity). More than 50%
      of the mass of the extractable organics of C-DEP eluted in the nonpolar Fraction
      1, and only ~20% eluted in the moderately polar Fractions 2 and 3. However, most
      of the mutagenicity eluted in Fractions 2 and 3, similar to A-DEP but different
      from N-DEP. HPLC-derived mutagrams of 62 sub-fractions per fraction confirmed
      that most of the mutagenicity was due to moderately polar compounds. The
      diagnostic strains identified a strong role for PAHs, nitroarenes, aromatic
      amines, and oxy-PAHs in the mutagenicity of C-DEP. Hierarchical clustering
      confirmed the importance of oxy-PAHs but not that of nitroarenes. To our
      knowledge this is the first use of hierarchical clustering to correlate chemical
      composition with the mutagenicity of a complex mixture. The chemical analysis and
      mutagenicity of C-DEP described here makes C-DEP suitable for additional
      toxicological studies.

PMID- 24105892
TI  - Pharmacogenetics in cardiovascular disease: the challenge of moving from promise
      to realization: concepts discussed at the Canadian Network and Centre for Trials
      Internationally Network Conference (CANNeCTIN), June 2009.
AB  - Pharmacogenetics in cardiovascular medicine brings the potential for personalized
      therapeutic strategies that improve efficacy and reduce harm. Studies evaluating
      the impact of genetic variation on pharmacologic effects have been undertaken for
      most major cardiovascular drugs, including antithrombotic agents, beta-adrenergic
      receptor blockers, statins, and angiotensin-converting enzyme inhibitors. Across
      these drug classes, many polymorphisms associated with pharmacodynamic,
      pharmacokinetic, or surrogate outcomes have been identified. However, their
      impact on clinical outcomes and their ability to improve clinical practice
      remains unclear. This review will examine the current clinical evidence
      supporting pharmacogenetic testing in cardiovascular medicine, provide clinical
      guidance based on the current evidence, and identify further steps needed to
      determine the utility of pharmacogenetics in cardiovascular care. 

PMID- 24105891
TI  - Some issues in predicting patient recruitment in multi-centre clinical trials.
AB  - A key paper in modelling patient recruitment in multi-centre clinical trials is
      that of Anisimov and Fedorov. They assume that the distribution of the number of
      patients in a given centre in a completed trial follows a Poisson distribution.
      In a second stage, the unknown parameter is assumed to come from a Gamma
      distribution. As is well known, the overall Gamma-Poisson mixture is a negative
      binomial. For forecasting time to completion, however, it is not the frequency
      domain that is important, but the time domain and that of Anisimov and Fedorov
      have also illustrated clearly the links between the two and the way in which a
      negative binomial in one corresponds to a type VI Pearson distribution in the
      other. They have also shown how one may use this to forecast time to completion
      in a trial in progress. However, it is not just necessary to forecast time to
      completion for trials in progress but also for trials that have yet to start.
      This suggests that what would be useful would be to add a higher level of the
      hierarchy: over all trials. We present one possible approach to doing this using
      an orthogonal parameterization of the Gamma distribution with parameters on the
      real line. The two parameters are modelled separately. This is illustrated using
      data from 18 trials. We make suggestions as to how this method could be applied
      in practice.

PMID- 24105893
TI  - Epstein-Barr DNA serology and positron-emission tomography imaging of the head
      and neck in pediatric transplant recipients.
AB  - OBJECTIVES/HYPOTHESIS: Epstein-Barr virus (EBV) infection is a potential
      precursor of post-transplantation lymphoproliferative disorder (PTLD) in the
      pediatric transplant patient. Positron-emission tomography (PET) imaging is
      increasingly utilized in this population to monitor for neoplasia and PTLD. We
      assess the association between EBV serum titers and Waldeyer's ring and cervical
      lymph node PET positivity in the pediatric transplant recipient. STUDY DESIGN:
      Retrospective analysis of EBV serology and PET imaging results in pediatric
      orthotopic liver transplantation (OLT) recipients. METHODS: Imaging results and
      laboratory data were reviewed for all pediatric OLT recipients from January 2005
      to July 2011 at a single institution. Charts were evaluated for PET positivity at
      Waldeyer's ring or cervical lymphatics, and for EBV serology results. Demographic
      data extracted include patient sex and age at transplantation. RESULTS: A total
      of 122 pediatric OLT recipients were reviewed. Twelve patients (10%) underwent
      PET imaging. Overall, four patients (33%) had evidence of PET positivity at
      Waldeyer's ring or cervical lymphatics. Five patients (42%) had positive EBV
      serology. There was a significant association between PET imaging results and EBV
      DNA serology results (P = .01). CONCLUSIONS: PTLD surveillance in the pediatric
      transplant recipient is an important component of long-term care in this
      population. Although PET imaging is a new modality in monitoring pediatric
      transplant recipients for early signs of PTLD, an association between EBV
      serology and PET imaging results appears to exist. With increased implementation,
      PET imaging will likely prove valuable in its ability to monitor the transplant
      recipient at risk for PTLD.

PMID- 24105894
TI  - Evaluation of Camelina sativa (L.) Crantz meal as an alternative protein source
      in ruminant rations.
AB  - BACKGROUND: Camelina sativa (CS) is an oilseed crop used for biofuel production.
      By-products from oil extraction are high in protein and can be used in ruminant
      rations; more information about their nutritive value is required also
      considering the antinutrional factor content of the by-products. The aim of this
      study was to evaluate the nutritive value of CS meal genotypes in comparison with
      canola. RESULTS: Ten CS genotypes and one canola cultivar were evaluated. Meals
      were obtained from seeds after solvent oil extraction. CS average crude protein
      (CP) content (g kg-1 dry matter) was 457. Numerical differences in lysine and
      sulfur amino acid content were observed among CS genotypes. Glucosinolate (mmol
      kg-1) content was higher for CS (23.1) than canola (7.2). Sinapine content (g kg
      1) was lower for CS (2.79) than for canola (4.32). Differences were observed
      among CS genotypes for rumen undegraded protein (RUP). Average RUP (g kg-1 CP)
      was 316 for CS and 275 for canola. CONCLUSIONS: CS meal has potential for use in
      ruminant rations as a high-quality protein source. In vivo studies are needed to
      compare CS with other protein sources used in cattle rations. Implementation of
      breeding programs for improved meal quality is recommend.

PMID- 24105895
TI  - Interictal networks in magnetoencephalography.
AB  - Epileptic networks involve complex relationships across several brain areas. Such
      networks have been shown on intracerebral EEG (stereotaxic EEG, SEEG), an
      invasive technique. Magnetoencephalography (MEG) is a noninvasive tool, which was
      recently proven to be efficient for localizing the generators of epileptiform
      discharges. However, despite the importance of characterizing non-invasively
      network aspects in partial epilepsies, only few studies have attempted to
      retrieve fine spatiotemporal dynamics of interictal discharges with MEG. Our goal
      was to assess the relevance of magnetoencephalography for detecting and
      characterizing the brain networks involved in interictal epileptic discharges. We
      propose here a semi-automatic method based on independent component analysis
      (ICA) and on co-occurrence of events across components. The method was evaluated
      in a series of seven patients by comparing its results with networks identified
      in SEEG. On both MEG and SEEG, we found that interictal discharges can involve
      remote regions which are acting in synchrony. More regions were identified in
      SEEG (38 in total) than in MEG (20). All MEG regions were confirmed by SEEG when
      an electrode was present in the vicinity. In all patients, at least one region
      could be identified as leading according to our criteria. A majority (71%) of MEG
      leaders were confirmed by SEEG. We have therefore shown that MEG measurements can
      extract a significant proportion of the networks visible in SEEG. This suggests
      that MEG can be a useful tool for defining noninvasively interictal epileptic
      networks, in terms of regions and patterns of connectivity, in search for a
      "primary irritative zone".

PMID- 24105896
TI  - Opening or closing the lock? When reactivity is the key to biological activity.
AB  - Thiol-mediated processes play a key role to induce or inhibit inflammation
      proteins. Tailoring the reactivity of electrophiles can enhance the selectivity
      to address only certain surface cysteines. Fourteen 2',3,4,4'
      tetramethoxychalcones with different alpha-X substituents (X=H, F, Cl, Br, I, CN,
      Me, p-NO2-C6H4, Ph, p-OMe-C6H4, NO2, CF3, COOEt, COOH) were synthesized,
      containing the potentially electrophilic alpha,beta-unsaturated carbonyl unit.
      The assessment of their reactivity as electrophiles in thia-Michael additions
      with cysteamine shows a change in the reactivity of more than six orders of
      magnitude. Moreover, a clear correlation between their reactivity and an
      influence on the inflammation proteins heme oxygenase-1 (HO-1) and the inducible
      NO synthase (iNOS) is demonstrated. As the biologically most active compound, the
      alpha-CF3 -chalcone is shown to inhibit the NO production in RAW264.7 mouse
      macrophages in the nanomolar range.

PMID- 24105897
TI  - What do you mean by transcription rate?: the conceptual difference between
      nascent transcription rate and mRNA synthesis rate is essential for the proper
      understanding of transcriptomic analyses.
AB  - mRNA synthesis in all organisms is performed by RNA polymerases, which work as
      nanomachines on DNA templates. The rate at which their product is made is an
      important parameter in gene expression. Transcription rate encompasses two
      related, yet different, concepts: the nascent transcription rate, which measures
      the in situ mRNA production by RNA polymerase, and the rate of synthesis of
      mature mRNA, which measures the contribution of transcription to the mRNA
      concentration. Both parameters are useful for molecular biologists, but they are
      not interchangeable and they are expressed in different units. It is important to
      distinguish when and where each one should be used. We propose that for
      functional genomics the use of nascent transcription rates should be restricted
      to the evaluation of the transcriptional process itself, whereas mature mRNA
      synthesis rates should be employed to address the transcriptional input to mRNA
      concentration balance leading to variation of gene expression. 

PMID- 24105898
TI  - Mitochondrial ascorbic acid is responsible for enhanced susceptibility of U937
      cells to the toxic effects of peroxynitrite.
AB  - Otherwise nontoxic levels of peroxynitrite promote toxicity in U937 cells pre
      exposed to low micromolar concentrations of l-ascorbic acid (AA). This event was
      associated with the mitochondrial accumulation of the vitamin and with the early
      formation of secondary reactive oxygen species and DNA single-strand breaks. The
      same concentrations of peroxynitrite, however, failed to elicit detectable
      effects in cells pre-exposed to dehydroascorbic acid (DHA), in which
      mitochondrial accumulation of vitamin C did not occur despite the identical
      cytosolic levels. Coherently, oxidation of extracellular AA failed to affect the
      intracellular concentration of the vitamin, but nevertheless prevented its
      mitochondrial localization as well as the enhanced response to peroxynitrite.
      Furthermore, in cells postincubated in vitamin C-free medium, time-dependent loss
      of mitochondrial AA was paralleled by a progressive decline of susceptibility to
      peroxynitrite, under the same conditions in which cells retained about half of
      the initial AA. Using different experimental approaches, we finally showed that
      the enhancing effects of AA are mediated by events associated with peroxynitrite
      dependent superoxide/H2 O2 formation in the mitochondrial respiratory chain.
      Collectively, these results indicate that mitochondria actively take up vitamin C
      as AA and respond to otherwise inactive concentrations of peroxynitrite with the
      mitochondrial formation of secondary species responsible for DNA damage and
      toxicity. DHA preloading, while leading to the accumulation of identical levels
      of vitamin C, fails to produce these effects because of the poor mitochondrial
      accumulation of the vitamin.

PMID- 24105899
TI  - Construction of a biomimetic peroxynitrite-generating platform: a two-component
      system to synthesize peroxynitrite in situ under the control of light.
AB  - Surge protector: a two-component peroxynitrite-generating platform has been
      engineered to release peroxynitrite (PN) in situ under the control of light. The
      system, which is constructed by layering sol-gel matrices containing xanthine
      oxidase (bottom layer) and a metal nitrosyl (top layer), allows studies of PN
      chemistry at varying fluxes of its precursors.

PMID- 24105900
TI  - The use of visual barriers to reduce aggression among a group of marabou storks
      (Leptoptilos crumeniferus).
AB  - Marabou storks are one of the most commonly held birds in zoos, but the captive
      population faces challenges related to high mortality. One of the most common
      causes of death among captive marabou storks is conspecific aggression. There is
      a pressing need to better understand how to manage this aggression. One method
      that has been used successfully to reduce aggression in other species is the
      addition of visual barriers to the enclosure, though there are no published
      studies on their effect on storks. We studied the behavioral changes in a group
      of 2.2 marabou storks following the addition of two shade cloth barriers to their
      enclosure; we documented all occurrences of aggressive behavior, as well as time
      spent proximate to the barriers (or the space between barrier posts, when the
      shade cloth was removed) and time spent using the barriers to block the view of
      other storks. The presence of the shade cloth did not change the amount of time
      storks spent proximate to the barriers, nor did they spend more than 2% of their
      time using the barriers to block other storks, but the presence of the barriers
      significantly reduced displacement activity. Barriers may afford captive marabou
      storks an important means of escaping conflict, as flight-restriction and housing
      in an enclosure can limit their opportunities to give a signal of retreat or
      submission.

PMID- 24105901
TI  - Comparing options for pair housing rhesus macaques using behavioral welfare
      measures.
AB  - In a biomedical research environment, research or management procedures may
      render continuous full contact pairing of rhesus macaques (Macaca mulatta)
      unfeasible. This study aimed to determine whether separation on a frequent basis
      or housing in adjacent cages with tactile contact interferes with the behavioral
      benefits of continuous full contact. Behavioral data (1260 hours) were collected
      from 32 adult females and 16 adult males housed at two National Primate Research
      Centers. Subjects were studied in four housing conditions: single housing, full
      contact pair housing, intermittent contact pair housing, and protected contact
      housing. After introduction, each pair was housed in each of the three social
      housing conditions in varying order. Among females, but not males, introducing
      animals into full and intermittent contact reduced levels of abnormal behavior.
      There was a trend toward this reduction in protected contact. In both females and
      males, full and intermittent contact was associated with lower levels of anxiety
      related behavior, but protected contact was not. Females spent more time inactive
      in protected contact than either full or intermittent contact, and males showed a
      trend toward less inactivity following introduction into full contact. Both sexes
      showed less affiliation in protected contact compared to the other forms of
      social housing. Agonistic behavior among females was not affected by housing
      condition; among males, levels were equivalent in full and intermittent contact
      but were higher in intermittent than protected contact. Frequent separation of
      pairs does not appear to detract from the behavioral benefits of pair housing.
      Separation by a barrier permitting tactile contact is inferior to other forms of
      social housing but showed modest improvements over single housing nonetheless.
      This study can guide the provision of social contact to rhesus macaques under
      conditions restricting pairs from continuous full contact.

PMID- 24105902
TI  - P-doped graphene obtained by pyrolysis of modified alginate as a photocatalyst
      for hydrogen generation from water-methanol mixtures.

PMID- 24105903
TI  - A resorbable shape-memory starch-based stent for the treatment of salivary ducts
      under sialendoscopic surgery.
AB  - OBJECTIVES/HYPOTHESIS: In sialendoscopy, stents are often used to keep the
      salivary duct open after surgery. These stents need to be removed. Recently, our
      group developed a new starch-based shape-memory material that is a widespread
      degradable polymer. Such a device could be manufactured into a deployable
      resorbable stent to keep the salivary duct open before in situ degradation. An
      experimental test was performed to establish a methodology and to evaluate the
      feasibility of the starch stent implantation in an animal model with clinical
      equipment. STUDY DESIGN: Evaluation of different formulations-potato and high
      amylose content maize starch without and with plasticizer-with laboratory bench
      top testing and in vivo evaluation in a large-animal model. METHODS: Starch-based
      stents were manufactured. They were evaluated for their shape-memory properties
      (water, 37 degrees C) and their degradability in simulated saliva in both static
      and flow conditions mimicking salivary flow in the submandibular duct. A pilot
      study of stent implantation was then performed in vivo in a large-animal model to
      assess that the stent dimensions were consistent for implantation in the
      submandibular duct. RESULTS: Stents made from plasticized starch had the required
      shape-memory properties to be used as self-deploying stents. However, starch
      based stents were rapidly hydrolyzed in simulated saliva. Stents could be
      directly inserted in the dilated salivary duct in a pig model without harming the
      epithelium. CONCLUSIONS: Shape-memory stents with suitable geometry for
      sialendoscopic surgical procedure can be fabricated and inserted in the
      submandibular duct. Starch-based stents can be used in other pathologies with
      less alpha-amylase content in the surrounding medium. LEVEL OF EVIDENCE: NA.

PMID- 24105904
TI  - Epidermal and dermal integumentary structures of ankylosaurian dinosaurs.
AB  - Ankylosaurian dinosaurs are most notable for their abundant and morphologically
      diverse osteoderms, which would have given them a spiky appearance in life.
      Isolated osteoderms are relatively common and provide important information about
      the structure of the ankylosaur dermis, but fossilized impressions of the soft
      tissue epidermis of ankylosaurs are rare. Nevertheless, well-preserved integument
      exists on several ankylosaur fossils that shows osteoderms were covered by a
      single epidermal scale, but one or many millimeter-sized ossicles may be present
      under polygonal, basement epidermal scales. Evidence for the taxonomic utility of
      ankylosaurid epidermal scale architecture is presented for the first time. This
      study builds on previous osteological work that argues for a greater diversity of
      ankylosaurids in the Dinosaur Park Formation of Alberta than has been
      traditionally recognized and adds to the hypothesis that epidermal skin
      impressions are taxonomically relevant across diverse dinosaur clades.

PMID- 24105905
TI  - A periodic array of nano-scale parallel slats for high-efficiency electroosmotic
      pumping.
AB  - It is known that the eletroosmotic (EO) flow rate through a nano-scale channel is
      extremely small. A channel made of a periodic array of slats is proposed to
      effectively promote the EO pumping, and thus greatly improve the EO flow rate.
      The geometrically simple array is complicated enough that four length scales are
      involved: the vertical period 2L, lateral period 2aL, width of the slat 2cL as
      well as the Debye length lambdaD. The EO pumping rate is determined by the
      normalized lengths: a, c, or the perforation fraction of slats eta=1-(c/a) and
      the dimensionless electrokinetic width K=L/lambdaD. In a nano-scale channel, K is
      of order unity or less. EO pumping in both longitudinal and transverse directions
      (denoted as longitudinal EO pumping (LEOP) and transverse EO pumping (TEOP),
      respectively) is investigated by solving the Debye-Huckel approximation and
      viscous electro-kinetic equation. The main findings include that (i) the EO
      pumping rates of LEOP for small K are remarkably improved (by one order of
      magnitude) when we have longer slats (a?1) and a large perforation fraction of
      slats (eta > 0.7); (ii) the EO pumping rates of TEOP for small K can also be much
      improved but less significantly with longer slats and a large perforation
      fraction of slats. Nevertheless, it must be noted that in practice K cannot be
      made arbitrarily small as the criterion of phic~0 for the reference potential at
      the channel center put lower bounds on K; in other words, there are geometrical
      limits for the use of the Poisson-Boltzmann equation. 

PMID- 24105906
TI  - LCST-type phase behavior induced by pillar[5]arene/ionic liquid host-guest
      complexation.
AB  - The host-guest complex of dipropoxypillar[5]arene and an ionic liquid 1,3
      dimethylimidazolium iodide is found to exhibit a lower critical solution
      temperature (LCST)-type phase transition in chloroform. This LCST-type phase
      behavior can be conveniently modulated by experimental parameters and can be
      easily combined with the ionic liquid for potential application in product and
      educt separation. 

PMID- 24105907
TI  - The social context and meaning of virginity loss among African American and
      Puerto Rican young adults in Hartford.
AB  - We describe virginity loss experiences of inner-city minority youth to understand
      the meaning attributed to first sex and the social and structural factors that
      contribute to early sexual debut. We interviewed 62 18-25-year-old African
      American and Puerto Rican Hartford men and women about their sexual and romantic
      life histories. Transcripts were coded in ATLAS.ti and analyzed for themes about
      virginity and sexual debut. We found different conceptions of virginity as a
      stigma to be lost, a normal part of growing up, and a gift to be given. The
      normative experience was consensual, early, and unplanned sexual debut. Inner
      city minority youth have similar feelings, motivations, and experiences of sexual
      debut as non-ethnic youth reported in the literature except they are far younger.
      We discuss structural factors that affect inner-city sexual scripts for early
      sexual debut and identify it as a health inequity. 

PMID- 24105908
TI  - A fluorescent probe for investigating the activation of anticancer platinum(IV)
      prodrugs based on the cisplatin scaffold.

PMID- 24105909
TI  - Gender-related safety and efficacy of cardiac resynchronization therapy.
AB  - BACKGROUND: Cardiac resynchronization therapy (CRT) is an established therapy for
      patients with chronic heart failure (CHF) and a broad QRS complex. Gender-related
      safety and efficacy data are necessary for informed patient decision-making for
      female patients with CHF. The aim of the study was to assess the effects of
      gender on the outcome of CRT in highly symptomatic heart failure patients.
      HYPOTHESIS: Gender may have an effect on the outcome of heart failure patients
      undergoing cardiac resynchronisation therapy. METHODS: The study analyzed the 2
      year follow-up of 393 New York Heart Association (NYHA) class III/IV patients
      with a class I CRT indication enrolled in the Management of Atrial Fibrillation
      Suppression in AF-HF Comorbidity Therapy (MASCOT) study. RESULTS: In female
      patients (n = 82), compared with male patients (n = 311), CHF was more often due
      to dilated cardiomyopathy (74% vs 44%, respectively; P < 0.0001). Females also
      had a more impaired quality-of-life score and a smaller left ventricular end
      diastolic diameter (LVEDD). Women were less likely than men to have received a
      CRT defibrillator (35% vs 61%, respectively; P < 0.0001). After 2 years, the
      devices had delivered more biventricular pacing in women than in men (96% +/- 13%
      vs 94% +/- 13%, respectively; P < 0.0004). Women had a greater reduction in LVEDD
      than did men (-8.2 mm +/- 11.1 mm vs -1.1 mm +/- 22.1 mm, respectively; P <
      0.02). Both genders improved similarly in NYHA functional class. Women reported
      greater improvement than men in quality-of-life score (-21.1 +/- 26.5 vs -16.2 +/
      22.1, respectively; P < 0.0001). After adjustment for cardiovascular history,
      women had lower all-cause mortality (P = 0.0007), less cardiac death (P = 0.04),
      and fewer hospitalizations for worsening heart failure (P = 0.01). CONCLUSIONS:
      Females exhibited a better response to CRT than did males. Because females have
      such impressive benefits from CRT, improved screening and advocacy for CRT
      implantation in women should be considered.

PMID- 24105911
TI  - A turn-on indole-based sensor for hydrogen sulfate ion.
AB  - A simple indole-based receptor 1 was prepared by a simple Schiff-base reaction of
      1H-indole-3-carbaldehyde with ethane 1,2-diamine and its fluoroionophoric
      properties toward anions were investigated. Indole-based receptor 1 acts as a
      selective turn-on fluorescent sensor for HSO4(-) in methanol among a series of
      tested anions. Fluorescence spectroscopy, ultraviolet and nuclear magnetic
      resonance imaging support that the HSO4(-) indeed interacted with imine nitrogen
      and the proton of nitrogen in indole ring.

PMID- 24105910
TI  - How do taste cells lacking synapses mediate neurotransmission? CALHM1, a voltage
      gated ATP channel.
AB  - CALHM1 was recently demonstrated to be a voltage-gated ATP-permeable ion channel
      and to serve as a bona fide conduit for ATP release from sweet-, umami-, and
      bitter-sensing type II taste cells. Calhm1 is expressed in taste buds exclusively
      in type II cells and its product has structural and functional similarities with
      connexins and pannexins, two families of channel protein candidates for ATP
      release by type II cells. Calhm1 knockout in mice leads to loss of perception of
      sweet, umami, and bitter compounds and to impaired gustatory nerve responses to
      these tastants. These new studies validate the concept of ATP as the primary
      neurotransmitter from type II cells to gustatory neurons. Furthermore, they
      identify voltage-gated ATP release through CALHM1 as an essential molecular
      mechanism of ATP release in taste buds. We discuss these new findings, as well as
      unresolved issues in peripheral taste signaling that we hope will stimulate
      future research. 

PMID- 24105913
TI  - Modeling of the diffusion MR signal in calibrated model systems and nerves.
AB  - Diffusion NMR is a powerful tool for gleaning microstructural information on
      opaque systems. In this work, the signal decay in single-pulsed-field gradient
      diffusion NMR experiments performed on a series of phantoms of increasing
      complexity, where the ground truth is known a priori, was modeled and used to
      identify microstructural features of these complex phantoms. We were able to
      demonstrate that, without assuming the number of components or compartments, the
      modeling can identify the number of restricted components, detect their sizes
      with an accuracy of a fraction of a micrometer, determine their relative
      populations, and identify and characterize free diffusion when present in
      addition to the components exhibiting restricted diffusion. After the accuracy of
      the modeling had been demonstrated, this same approach was used to study fixed
      nerves under different experimental conditions. It seems that this approach is
      able to characterize both the averaged axon diameter and the relative population
      of the different diffusing components in the neuronal tissues examined.

PMID- 24105912
TI  - Membrane biophysics define neuron and astrocyte progenitors in the neural
      lineage.
AB  - Neural stem and progenitor cells (NSPCs) are heterogeneous populations of self
      renewing stem cells and more committed progenitors that differentiate into
      neurons, astrocytes, and oligodendrocytes. Accurately identifying and
      characterizing the different progenitor cells in this lineage has continued to be
      a challenge for the field. We found previously that populations of NSPCs with
      more neurogenic progenitors (NPs) can be distinguished from those with more
      astrogenic progenitors (APs) by their inherent biophysical properties,
      specifically the electrophysiological property of whole cell membrane
      capacitance, which we characterized with dielectrophoresis (DEP). Here, we
      hypothesize that inherent electrophysiological properties are sufficient to
      define NPs and APs and test this by determining whether isolation of cells solely
      by these properties specifically separates NPs and APs. We found NPs and APs are
      enriched in distinct fractions after separation by electrophysiological
      properties using DEP. A single round of DEP isolation provided greater NP
      enrichment than sorting with PSA-NCAM, which is considered an NP marker.
      Additionally, cell surface N-linked glycosylation was found to significantly
      affect cell fate-specific electrophysiological properties, providing a molecular
      basis for the cell membrane characteristics. Inherent plasma membrane biophysical
      properties are thus sufficient to define progenitor cells of differing fate
      potential in the neural lineage, can be used to specifically isolate these cells,
      and are linked to patterns of glycosylation on the cell surface.

PMID- 24105914
TI  - Comparison of statistics in association tests of genetic markers for survival
      outcomes.
AB  - Computationally efficient statistical tests are needed in association testing of
      large scale genetic markers for survival outcomes. In this study, we explore
      several test statistics based on the Cox proportional hazards model for survival
      data. First, we consider the classical partial likelihood-based Wald and score
      tests. A revised way to compute the score statistics is explored to improve the
      computational efficiency. Next, we propose a Cox-Snell residual-based score test,
      which allows us to handle the controlling variables more conveniently. We also
      illustrated the incorporation of these three tests into a permutation procedure
      to adjust for the multiple testing. In addition, we examine a simulation-based
      approach proposed by Lin (2005) to adjust for multiple testing. We presented the
      comparison of these four statistics in terms of type I error, power, family-wise
      error rate, and computational efficiency under various scenarios via extensive
      simulation.

PMID- 24105915
TI  - Neuropsychological differential diagnosis of mild traumatic brain injury.
AB  - The diagnosis and evaluation of mild traumatic brain injury (mTBI) is reviewed
      from the perspective of meta-analyses of neuropsychological outcome, showing full
      recovery from a single, uncomplicated mTBI by 90 days post-trauma. Persons with
      history of complicated mTBI characterized by day-of-injury computed tomography or
      magnetic resonance imaging abnormalities, and those who have suffered prior mTBIs
      may or may not show evidence of complete recovery similar to that experienced by
      persons suffering a single, uncomplicated mTBI. Persistent post-concussion
      syndrome (PCS) is considered as a somatoform presentation, influenced by the non
      specificity of PCS symptoms which commonly occur in non-TBI samples and co-vary
      as a function of general life stress, and psychological factors including symptom
      expectation, depression and anxiety. A model is presented for forensic evaluation
      of the individual mTBI case, which involves open-ended interview, followed by
      structured interview, record review, and detailed neuropsychological testing.
      Differential diagnosis includes consideration of other neurologic and psychiatric
      disorders, symptom expectation, diagnosis threat, developmental disorders, and
      malingering.

PMID- 24105916
TI  - Dengue, Japanese encephalitis and Chikungunya virus antibody prevalence among
      captive monkey (Macaca nemestrina) colonies of Northern Thailand.
AB  - The potential of macaque Macaca nemestrina leonina in Thailand to be infected by
      endemic arboviruses was assessed. The prevalence of antibodies of three
      arboviruses actively circulating in Thailand was determined by Plaque Reduction
      Neutralization assay procedures using samples from captive colonies in Northern
      Thailand. Out of 38 macaques, 9 (24%) presented reacting antibodies against
      dengue virus, 5 (13%) against Japanese encephalitis virus, and 4 (10%) against
      Chikungunya virus. Our results indicate that the northern pig-tailed macaque in
      Thailand can be infected by these arboviruses, inferring therefore that their
      virus specific vectors have bitten them. Given that, northern pig-tailed macaque
      represents an abundant population, living in close range to human or in
      peridomestic setting, they could play a role as potential reservoir host for
      arboviruses circulating in Thailand.

PMID- 24105918
TI  - PAMLX: a graphical user interface for PAML.
AB  - This note announces pamlX, a graphical user interface/front end for the paml (for
      Phylogenetic Analysis by Maximum Likelihood) program package (Yang Z. 1997. PAML:
      a program package for phylogenetic analysis by maximum likelihood. Comput Appl
      Biosci. 13:555-556; Yang Z. 2007. PAML 4: Phylogenetic analysis by maximum
      likelihood. Mol Biol Evol. 24:1586-1591). pamlX is written in C++ using the Qt
      library and communicates with paml programs through files. It can be used to
      create, edit, and print control files for paml programs and to launch paml runs.
      The interface is available for free download at
      http://abacus.gene.ucl.ac.uk/software/paml.html.

PMID- 24105917
TI  - Polymyxins and analogues bind to ribosomal RNA and interfere with eukaryotic
      translation in vitro.
AB  - Looking for targets: while the bactericidal activity of polymyxins is attributed
      to changes in membrane permeation, we show that these antibiotics can bind
      prokaryotic and eukaryotic A-sites, domains responsible for translational
      decoding. Polymyxin B, colistin and analogues also hinder eukaryotic translation
      in vitro. These new targets and effects might be partially responsible for the
      plethora of adverse effects by these potent bactericidal agents.

PMID- 24105919
TI  - Quantitative analysis and discrimination of steamed and non-steamed rhizomes of
      Curcuma wenyujin by GC-MS and HPLC.
AB  - Simple gas chromatography-mass spectrometry (GC-MS) and high-performance liquid
      chromatography (HPLC) methods were developed for quantifying eight volatile
      compounds and 10 sesquiterpenoids, respectively. GC-MS analysis was performed on
      an HP-5MS capillary column (30 m*0.25 mm i.d.) coated with 0.25 MUm film 5%
      phenyl-95% methylpolysiloxane and selected ion monitoring was used for
      quantification. Four volatile and previously unquantified monoterpenoids were
      determined. HPLC analysis was performed on a C18 column with water and
      acetonitrile as mobile phase. The proposed method, determined 10 non-polar and
      polar sesquiterpenoids simultaneously, which covered a wider polar range of
      analytes and had a more perfect resolution. Among them, five sesquiterpenoids
      were not determined before and some specific components, (4S,5S)-germacrone-4,5
      epoxide, curcumenone and dehydrocurdione were completely separated for the first
      time. Both methods were validated for linearity, limit of detection and
      quantification, precision, accuracy, recovery and system suitability. The methods
      were simple, effective, reliable and successfully applied to global detection and
      analysis of volatile and non-volatile components of steamed and non-steamed
      rhizomes of Curcuma wenyujin (Wen-E-Zhu (WEZ) and Pian-Jiang-Huang (PJH)).
      Multivariate statistical analysis was employed to distinguish PJH and WEZ and
      seven chemical components, including (4S,5S)-germacrone-4,5-epoxide, curcumenone,
      beta-elemene, curzerene, borneol, isoborneol and camphor, were screened as
      chemical markers. The present study provided a promising method for accurate
      discrimination of the herbal medicines with the same origin. 

PMID- 24105920
TI  - Formation of aromatics in thermally induced reactions of chemically bonded RP-C18
      stationary phase.
AB  - In continuation of the research on the thermally induced chemical transformation
      of the silica-based chemically bonded stationary phases (C18), the oxidative
      cleavage of the silicon-carbon bonds with hydrogen peroxide and potassium
      fluoride was utilized, followed by the gas chromatography coupled with mass
      spectrometry (GC-MS) study of the resulting products. These investigations
      allowed determination of the probable structures of certain thermal modification
      products as the various different alkyl derivatives of the phenylsilane ligands.
      Apart from aromatic compounds, the products with unsaturated bonds and carbonyl
      functionalities were found in the analyzed extracts. The analysis of the GC-MS
      chromatograms reveals that under the applied working conditions, the investigated
      process runs with relatively low yields. 

PMID- 24105921
TI  - Relatively high rates of G:C -> A:T transitions at CpG sites were observed in
      certain epithelial tissues including pancreas and submaxillary gland of adult big
      blue(r) mice.
AB  - With few exceptions, spontaneous mutation frequency and pattern are similar
      across tissue types and relatively constant in young to middle adulthood in wild
      type mice. Underrepresented in surveys of spontaneous mutations across murine
      tissues is the diversity of epithelial tissues. For the first time, spontaneous
      mutations were detected in pancreas and submaxillary gland and compared with
      kidney, lung, and male germ cells from five adult male Big Blue(r) mice. Mutation
      load was assessed quantitatively through measurement of mutant and mutation
      frequency and qualitatively through identification of mutations and
      characterization of recurrent mutations, multiple mutations, mutation pattern,
      and mutation spectrum. A total of 9.6 million plaque forming units were screened,
      226 mutants were collected, and 196 independent mutations were identified. Four
      novel mutations were discovered. Spontaneous mutation frequency was low in
      pancreas and high in the submaxillary gland. The submaxillary gland had multiple
      recurrent mutations in each of the mice and one mutant had two independent
      mutations. Mutation patterns for epithelial tissues differed from that observed
      in male germ cells with a striking bias for G:C to A:T transitions at CpG sites.
      A comprehensive review of lacI spontaneous mutation patterns in young adult mice
      and rats identified additional examples of this mutational bias. An overarching
      observation about spontaneous mutation frequency in adult tissues of the mouse
      remains one of stability. A repeated observation in certain epithelial tissues is
      a higher rate of G:C to A:T transitions at CpG sites and the underlying
      mechanisms for this bias are not known.

PMID- 24105922
TI  - Fluorogenic ATP analogues for online monitoring of ATP consumption: observing
      ubiquitin activation in real time.

PMID- 24105923
TI  - Tissue- and column-specific measurements from multi-parameter mapping of the
      human cervical spinal cord at 3 T.
AB  - The aim of this study was to quantify a range of MR parameters [apparent proton
      density, longitudinal relaxation time T1, magnetisation transfer (MT) ratio, MT
      saturation (which represents the additional percentage MT saturation of the
      longitudinal magnetisation caused by a single MT pulse) and apparent transverse
      relaxation rate R2*] in the white matter columns and grey matter of the healthy
      cervical spinal cord. The cervical cords of 13 healthy volunteers were scanned at
      3 T using a protocol optimised for multi-parameter mapping. Intra-subject co
      registration was performed using linear registration, and tissue- and column
      specific parameter values were calculated. Cervical cord parameter values
      measured from levels C1-C5 in 13 subjects are: apparent proton density, 4822 +/-
      718 a.u.; MT ratio, 40.4 +/- 1.53 p.u.; MT saturation, 1.40 +/- 0.12 p.u.; T1 =
      1848 +/- 143 ms; R2* = 22.6 +/- 1.53 s(-1). Inter-subject coefficients of
      variation were low in both the cervical cord and tissue- and column-specific
      measurements, illustrating the potential of this method for the investigation of
      changes in these parameters caused by pathology. In summary, an optimised
      cervical cord multi-parameter mapping protocol was developed, enabling tissue-
      and column-specific measurements to be made. This technique has the potential to
      provide insight into the pathological processes occurring in the cervical cord
      affected by neurological disorders.

PMID- 24105924
TI  - Remote monitoring of implantable pacemakers: in-office setup significantly
      improves successful data transmission.
AB  - BACKGROUND: Remote wireless follow-up of implanted pacemakers (PM) has become an
      attractive method of follow-up. Although wireless PM follow-up has several
      advantages compared with transtelephonic and office-based follow-up, its utility
      depends on successful transmission. HYPOTHESIS: Initial in-office setup of
      wireless PM will improve transmission rate as compared with home setup. METHODS:
      A total of 202 consecutive patients from 2 medical centers were included in this
      retrospective study. Patients in the home setup group (N = 101) had traditional
      home setup of wireless PM, whereas patients in the in-office group (N = 101) had
      setup of PMs by allied health professionals during the postoperative office
      visit. Successful transmission was defined as successful initial wireless
      transmission of PM data by 2 months postimplant. RESULTS: Of the 101 patients in
      the home setup group, 22 (22%) patients had successful transmission. Of the 101
      patients in the in-office group, 92 (91%) patients had successful transmission (P
      < 0.0001). Logistic regression analysis showed that that the in-office group was
      independently associated with successful transmission (odds ratio: 114.5; 95%
      confidence interval: 32.1-408.4; P < 0.0001). CONCLUSIONS: In patients implanted
      with PM capable of remote wireless data transmission, initial home setup of the
      wireless monitoring device was frequently unsuccessful. In-office PM setup was
      associated with a significantly higher rate of successful transmission.

PMID- 24105925
TI  - HIF-prolyl hydroxylase 2 inhibition enhances the efficiency of mesenchymal stem
      cell-based therapies for the treatment of critical limb ischemia.
AB  - Upregulation of hypoxia-inducible transcription factor-1alpha (HIF-1alpha),
      through prolyl-hydroxylase domain protein (PHD) inhibition, can be thought of as
      a master switch that coordinates the expression of a wide repertoire of genes
      involved in regulating vascular growth and remodeling. We aimed to unravel the
      effect of specific PHD2 isoform silencing in cell-based strategies designed to
      promote therapeutic revascularization in patients with critical limb ischemia
      (CLI). PHD2 mRNA levels were upregulated whereas that of HIF-1alpha were
      downregulated in blood cells from patients with CLI. We therefore assessed the
      putative beneficial effects of PHD2 silencing on human bone marrow-derived
      mesenchymal stem cells (hBM-MSC)-based therapy. PHD2 silencing enhanced hBM-MSC
      therapeutic effect in an experimental model of CLI in Nude mice, through an
      upregulation of HIF-1alpha and its target gene, VEGF-A. In addition, PHD2
      transfected hBM-MSC displayed higher protection against apoptosis in vitro and
      increased rate of survival in the ischemic tissue, as assessed by Fluorescence
      Molecular Tomography. Cotransfection with HIF-1alpha or VEGF-A short interfering
      RNAs fully abrogated the beneficial effect of PHD2 silencing on the proangiogenic
      capacity of hBM-MSC. We finally investigated the effect of PHD2 inhibition on the
      revascularization potential of ischemic targeted tissues in the diabetic
      pathological context. Inhibition of PHD-2 with shRNAs increased postischemic
      neovascularization in diabetic mice with CLI. This increase was associated with
      an upregulation of proangiogenic and proarteriogenic factors and was blunted by
      concomitant silencing of HIF-1alpha. In conclusion, silencing of PHD2, by the
      transient upregulation of HIF-1alpha and its target gene VEGF-A, might improve
      the efficiency of hBM-MSC-based therapies.

PMID- 24105926
TI  - Testing increases suggestibility for narrative-based misinformation but reduces
      suggestibility for question-based misinformation.
AB  - A number of recent studies have found that recalling details of an event
      following its occurrence can increase people's suggestibility to later presented
      misinformation. However, several other studies have reported the opposite result,
      whereby earlier retrieval can reduce subsequent eyewitness suggestibility. In the
      present study, we investigated whether differences in the way misinformation is
      presented can modulate the effects of testing on suggestibility. Participants
      watched a video of a robbery and some were questioned about the event immediately
      afterwards. Later, participants were exposed to misinformation in a narrative
      (Experiment 1) or in questions (Experiment 2). Consistent with previous studies,
      we found that testing increased suggestibility when misinformation was presented
      via a narrative. Remarkably, when misinformation was presented in questions,
      testing decreased suggestibility.

PMID- 24105927
TI  - Selective adsorption of functionalized nanoparticles to patterned polymer brush
      surfaces and its probing with an optical trap.
AB  - The site-specific attachment of nanoparticles is of interest for biomaterials or
      biosensor applications. Polymer brushes can be used to regulate this adsorption,
      so the conditions for selective adsorption of phosphonate-functionalized
      nanoparticles onto micropatterned polymer brushes with different functional
      groups are optimized. By choosing the strong polyelectrolytes poly(3-sulfopropyl
      methacrylate), poly(sulfobetaine methacrylate), and poly[2-(methacryloyloxy)ethyl
      trimethylammonium chloride], it is possible to direct the adsorption of
      nanoparticles to specific regions of the patterned substrates. A pH-dependent
      adsorption can be achieved by using the polycarboxylate brush poly(methacrylic
      acid) (PMAA) as substrate coating. On PMAA brushes, the nanoparticles switch from
      attachment to the brush regions to attachment to the grooves of a patterned
      substrate on changing the pH from 3 to 7. In this manner, patterned substrates
      are realized that assemble nanoparticles in pattern grooves, in polymer brush
      areas, or substrates that resist the deposition of the nanoparticles. The
      nanoparticle deposition can be directed in a pH-dependent manner on a weak
      polyelectrolyte, or is solely charge-dependent on strong polyelectrolytes. These
      results are correlated with surface potential measurements and show that an
      optical trap is a versatile method to directly probe interactions between
      nanoparticles and polymer brushes. A model for these interactions is proposed
      based on the optical trap measurements. 

PMID- 24105928
TI  - Synthesis of vicinal aminoalcohols by stereoselective aza-Wacker cyclizations:
      access to (-)-acosamine by redox relay.

PMID- 24105929
TI  - Two novel splice variants of SOX2OT, SOX2OT-S1, and SOX2OT-S2 are coupregulated
      with SOX2 and OCT4 in esophageal squamous cell carcinoma.
AB  - Long noncoding RNAs (lncRNAs) have emerged as new regulators of stem cell
      pluripotency and tumorigenesis. The SOX2 gene, a master regulator of
      pluripotency, is embedded within the third intron of a lncRNA known as SOX2
      overlapping transcript (SOX2OT). SOX2OT has been suspected to participate in
      regulation of SOX2 expression and/or other related processes; nevertheless, its
      potential involvement in tumor initiation and/or progression is unclear. Here, we
      have evaluated a possible correlation between expression patterns of SOX2OT and
      those of master regulators of pluripotency, SOX2 and OCT4, in esophageal squamous
      cell carcinoma (ESCC) tissue samples. We have also examined its potential
      function in the human embryonic carcinoma stem cell line, NTERA2 (NT2), which
      highly expresses SOX2OT, SOX2, and OCT4. Our data revealed a significant
      coupregulation of SOX2OT along with SOX2 and OCT4 in tumor samples, compared to
      the non-tumor tissues obtained from the margin of same tumors. We also identified
      two novel splice variants of SOX2OT (SOX2OT-S1 and SOX2OT-S2) which coupregulated
      with SOX2 and OCT4 in ESCCs. Suppressing SOX2OT variants caused a profound
      alteration in cell cycle distribution, including a 5.9 and 6.9 time increase in
      sub-G1 phase of cell cycle for SOX2OT-S1 and SOX2OT-S2, respectively. The
      expression of all variants was significantly diminished, upon the induction of
      neural differentiation in NT2 cells, suggesting their potential functional links
      to the undifferentiated state of the cells. Our data suggest a part for SOX2OT
      spliced variants in tumor initiation and/or progression as well as regulating
      pluripotent state of stem cells.

PMID- 24105930
TI  - Ab initio molecular dynamics study of ethylene adsorption onto Si(001) surface:
      short-time Fourier transform analysis of structural coordinate autocorrelation
      function.
AB  - The reaction dynamics of ethylene adsorption onto the Si(001) surface have been
      studied by combining density functional theory-based molecular dynamics
      simulations with molecular adsorption sampling scheme for investigating all kinds
      of reaction pathways and corresponding populations. Based on the calculated
      results, three possible reaction pathways--the indirect adsorption, the direct
      adsorption, and the repelling reaction--have been found. First, the indirect
      adsorption, in which the ethylene (C2H(4(ads))) forms the pi-bonded C2H(4(ads))
      with the buckled-down Si atom to adsorb on the Si(001) surface and then turns
      into the di-sigma-bonded C2H(4(ads)), is the major reaction pathway. The short
      time Fourier transform analysis of structural coordinate autocorrelation function
      is performed to further investigate the evolution of different vibrational modes
      along this indirect reaction pathway. This analysis illustrates that the Infrared
      (IR) inactive peak of the C=C stretching mode of the pi-bonded C2 H4(ads) shifts
      to the IR inactive peak of the C-C stretching mode of di-sigma-bonded
      C2H(4(ads)), which is in a good agreement with the IR inactive peak of the C=C
      stretching mode vanished in the vibrational spectrum at 150 K (Nagao et al., J.
      Am. Chem. Soc. 2004, 126, 9922). Second, the direct adsorption, in which the di
      sigma-bonded C2H(4(ads)) is formed directly with the Si intradimer or the Si
      interdimer on the Si(001) surface, is the less significant reaction pathway. This
      reaction pathway leads to the C-C stretching mode and the C-H stretching mode of
      the di-sigma-bonded C2H(4(ads)) appeared in the vibrational spectra at 48 and 150
      K, respectively (Nagao et al., J. Am. Chem. Soc. 2004, 126, 9922). Finally, the
      repelling reaction, in which the C2H(4(g)) first interacts with the Si dimer and
      then is repelled by Si atoms, is the least important reaction pathway.
      Consequently, neither the pi-bonded C2H(4(ads)) nor the di-sigma-bonded
      C2H(4(ads)) is formed on the Si(001) surface.

PMID- 24105932
TI  - CLARITY or the invisible brain.

PMID- 24105933
TI  - New evidence for self-medication in bonobos: Manniophyton fulvum leaf- and
      stemstrip-swallowing from LuiKotale, Salonga National Park, DR Congo.
AB  - The swallowing of entire leaves by apes across Africa without chewing has been
      observed for over 40 plant species. Here we add evidence for (a) a new site,
      LuiKotale where leaf-swallowing of Manniophyton fulvum (Euphorbiaceae) is
      observed in bonobos, (b) a so far unreported ingestion of unchewed stemstrips of
      M. fulvum, we name stemstrip-swallowing; and (c) a test of some of the
      requirements put forward by Huffman for the assessment of plants ingested for
      medical purpose. As ecological correlates we analyzed M. fulvum phenological data
      and examined 1,094 dung piles collected between 2002 and 2009. By that we
      assessed availability and choice of leaves. In addition, we provide the first
      full description of the behavior related to this plant species' use by
      chimpanzees or bonobos using 56 bouts of M. fulvum ingestion observed between
      October 2007 and February 2010. With these data we tested and met 4 of the 6
      requirements given by Huffman, supporting ingestion of this species as self
      medication. Despite species' year-round availability and abundance, M. fulvum was
      ingested only at specific times, in very small amounts, and by a small proportion
      of individuals per party. In the absence of our own parasitological data, we used
      M. fulvum swallowing as evidence for parasite infestation, and seasonality as a
      proxy for stressors underlying seasonal fluctuation and impacting immune
      responses. Using these indirect factors available, we investigated conditions for
      a parasite to develop to its infective stage as well as conditions for the host
      to cope with infections. Both rain and temperature were good predictors for M.
      fulvum ingestion. We discuss the use of M. fulvum with respect to its hispidity
      and subsequent purging properties and provide insight into its ethnomedicinal
      uses by humans, stimulating speculations about potentially additional
      pharmacological effects.

PMID- 24105931
TI  - Chemical approaches to detect and analyze protein sulfenic acids.
AB  - Orchestration of many processes relying on intracellular signal transduction is
      recognized to require the generation of hydrogen peroxide as a second messenger,
      yet relatively few molecular details of how this oxidant acts to regulate protein
      function are currently understood. This review describes emerging chemical tools
      and approaches that can be applied to study protein oxidation in biological
      systems, with a particular emphasis on a key player in protein redox regulation,
      cysteine sulfenic acid. While sulfenic acids (within purified proteins or simple
      mixtures) are detectable by physical approaches like X-ray crystallography,
      nuclear magnetic resonance and mass spectrometry, the propensity of these
      moieties to undergo further modification in complex biological systems has
      necessitated the development of chemical probes, reporter groups and analytical
      approaches to allow for their selective detection and quantification. Provided is
      an overview of techniques that are currently available for the study of sulfenic
      acids, and some of the biologically meaningful data that have been collected
      using such approaches.

PMID- 24105934
TI  - Validation of high-throughput genotoxicity assay screening using gammaH2AX in
      cell western assay on HepG2 cells.
AB  - In vitro genotoxicity tests used in regulatory toxicology studies are sensitive,
      but the occurrence of irrelevant positive results is high compared with
      carcinogenicity studies in rodents. Current in vitro genotoxicity tests are also
      often limited by relatively low throughput. The aim of this study was to validate
      an in vitro genotoxic assay in a 96-well plate format that allows the
      simultaneous examination of cytotoxicity and genotoxicity. The test is based on
      the quantification of the phosphorylation of the histone H2AX (gammaH2AX), which
      reflects a global genotoxic insult, using the In-Cell Western technique. The
      assay was evaluated on HepG2 cells by testing a list of 61 compounds recommended
      by the European Center for the Validation of Alternative Methods (ECVAM), whose
      genotoxic potential has already been characterized. The gammaH2AX assay on HepG2
      cell line was highly sensitive: 75% of the genotoxic compounds gave a positive
      result, and specific: 90-100% of nongenotoxic compounds gave negative results.
      Compared with the micronucleus genotoxicity assay using the same cell line and
      test compounds, the gammaH2AX assay was more sensitive and specific. In sum, the
      high-throughput gammaH2AX assay described here can accurately detect
      simultaneously the genotoxic and the cytotoxic potential of compounds with
      different modes of mutagenic action, notably those who required metabolic
      activation. The use of this assay in the early discovery phase of drug
      development may prove to be a valuable way to assess the genotoxic potential of
      xenobiotics.

PMID- 24105935
TI  - In situ study of the gas-phase electrolysis of water on platinum by NAP-XPS.
AB  - Chasing down the active state: Near-ambient-pressure X-ray photoelectron
      spectroscopy was used to study the surface of a Pt electrode during the oxygen
      evolution reaction (OER). A hydrated Pt metal phase with dissolved oxygen in the
      near-surface region is OER-active and considered to be the precursor of the
      analytically detected PtO2 , which is in fact the deactivation product of the
      electrode. 

PMID- 24105936
TI  - Conformational analysis of the anti-obesity drug lorcaserin in water: how to take
      advantage of long-range residual dipolar couplings.
AB  - The conformational state of 8-chloro-1-methyl-2,3,4,5-tetrahydro-1H-3-benzazepine
      hydrochloride (lorcaserin) in water has been determined on the basis of one-bond
      and long-range C-H residual dipolar coupling (RDC) data along with DFT
      computations and (3)J(HH) coupling-constant analysis. According to this analysis,
      lorcaserin exists as a conformational equilibrium of two crown-chair forms, of
      which the preferred conformation has the methyl group in an equatorial
      orientation.

PMID- 24105938
TI  - Linear and cyclic hybrids of alternating thiophene-amino acid units: synthesis
      and effects of chirality on conformation and molecular packing.
AB  - The dipeptide isostere 5-aminothiophene carboxylic acid has been combined with L
      phenylalanine moieties to provide linear and cyclic hybrid oligopeptides. A
      suitable protecting group strategy and appropriate coupling methods have been
      developed to guarantee a high degree of enantiopurity of the resulting amides.
      Cyclic tetraamides have been efficiently obtained by macrocyclization of the
      linear derivatives. In the case of racemized cyclization precursors, two
      diastereomeric macrocycles (S,S/R,R and meso) have been isolated. Their crystal
      structures show clear effects of the stereogenic centers on the ring
      conformations and molecular packing. 

PMID- 24105937
TI  - Toggling a conformational switch in Wnt/beta-catenin signaling: regulation of
      Axin phosphorylation. The phosphorylation state of Axin controls its scaffold
      function in two Wnt pathway protein complexes.
AB  - The precise orchestration of two opposing protein complexes - one in the
      cytoplasm (beta-catenin destruction complex) and the other at the plasma membrane
      (LRP6 signaling complex) - is critical for controlling levels of the
      transcriptional co-factor beta-catenin, and subsequent activation of the Wnt/beta
      catenin signal transduction pathway. The Wnt pathway component Axin acts as an
      essential scaffold for the assembly of both complexes. How the beta-catenin
      destruction and LRP6 signaling complexes are modulated following Wnt stimulation
      remains controversial. A recent study in Science by He and coworkers reveals an
      underlying logic for Wnt pathway control in which Axin phosphorylation toggles a
      switch between the active and inactive states. This mini-review focuses on this
      and two other recent studies that provide insight into the initial signaling
      events triggered by Wnt exposure. We emphasize regulation of the beta-catenin
      destruction and LRP6 signaling complexes and propose a framework for future work
      in this area. 

PMID- 24105939
TI  - Tuning the fluorescent response of a novel electroactive polymer with multiple
      stimuli.
AB  - A novel polymer featuring oligoaniline pendants that exhibits reversible
      electroactivity and good electrochromic properties with high contrast value,
      acceptable switching times, and excellent coloration efficiency is presented.
      This polymer can undergo reversible changes in fluorescence in response to
      reductive and oxidative chemical stimulus, pH, and electrical potential. The
      fluorescence switching operation shows reasonable reversibility and
      reproducibility when subjected to multiple stimuli. In this elegant fluorescence
      switching system, the oligoaniline pendants are used as fluorophore and
      regulatory units simultaneously. 

PMID- 24105940
TI  - Effects and outcomes in civilian and military traumatic brain injury:
      similarities, differences, and forensic implications.
AB  - Traumatic brain injury (TBI) is a prominent public health problem in both
      civilian and military settings. This article discusses similarities and
      differences in the assessment and treatment of TBI and the attendant forensic
      implications. Acute care and management of moderate/severe TBI tend to be similar
      across environments, as is the recognition of disability status in affected
      individuals. By contrast, an increased focus on mild TBI in recent years has
      resulted in a reliance on self-report and screening measures to validate the
      occurrence of events leading to injury. This has complicated assessment,
      treatment and subsequent medicolegal proceedings. The neuropsychological
      literature has provided significant guidance on these difficult issues, although
      the complexity of disability adjudication for active duty members of the military
      and veterans continues to pose challenges for clinicians in evaluative and
      treatment contexts.

PMID- 24105941
TI  - Structural and magnetic properties of 3d transition-metal-atom adsorption on
      perfect and defective graphene: a density functional theory study.
AB  - We systematically investigate the interactions and magnetic properties of a
      series of 3d transition-metal (TM; Sc-Ni) atoms adsorbed on perfect graphene
      (G6), and on defective graphene with a single pentagon (G5), a single heptagon
      (G7), or a pentagon-heptagon pair (G57) by means of spin-polarized density
      functional calculations. The TM atoms tend to adsorb at hollow sites of the
      perfect and defective graphene, except for G6Cr, G5Cr, and G5Ni. The binding
      energies of TMs on defective graphene are remarkably enhanced and show a V-shape,
      with G(N)Cr and G(N)Mn having the lowest binding energies. Furthermore,
      complicated element- and defect-dependent magnetic behavior is observed in
      G(N)TM. Particularly, the magnetic moments of G(N)TM linearly increase by about 1
      MUB and follow a hierarchy of G7TM<G57TM<G5TM as the TM varies from Sc to Mn, and
      the magnetic moments begin to decrease afterward; by choosing different types of
      defects, the magnetic moments can be tuned over a broad range, for example, from
      3 to 6 MUB for G(N)Cr. The intriguing element- and defect-dependent magnetic
      behavior is further understood from electron- and back-donation mechanisms.

PMID- 24105942
TI  - Autosomal male determination in a spinosad-resistant housefly strain from
      Denmark.
AB  - BACKGROUND: The housefly, Musca domestica L., is a global pest and has developed
      resistance to most insecticides applied for its control. The insecticide spinosad
      plays an important role in housefly control. Females of the Danish housefly
      strain 791spin are threefold more resistant to spinosad than males in this
      strain. The factor responsible for spinosad resistance in the strain is unknown,
      but previous studies suggest a role of cytochrome P450s for detoxification of
      spinosad. Sex determination in the housefly is controlled by a male-determining
      factor (M), either located on the Y chromosome or on one of the five autosomes (I
      to V). RESULTS: The authors performed a series of crosses and backcrosses,
      starting with cross of 791spin and the susceptible reference strain aabys
      (bearing morphological mutations on each autosome). These flies were evaluated
      for gender and bioassayed to determine levels of resistance to spinosad. Sex
      determination in 791spin is due to a male factor on autosome 3. CONCLUSIONS: The
      most likely explanation for the differentiation of spinosad resistance between
      males and females is a recessive spinosad resistance factor on autosome III.

PMID- 24105943
TI  - Cellvibrio diazotrophicus sp. nov., a nitrogen-fixing bacteria isolated from the
      rhizosphere of salt meadow plants and emended description of the genus
      Cellvibrio.
AB  - Two Gram-reaction-negative, aerobic, nitrogen-fixing, rod-shaped bacteria,
      designated strains E20 and E50(T), were isolated from the rhizosphere of salt
      meadow plants Plantago winteri and Hordeum secalinum, respectively, near
      Munzenberg, Germany. Based on the 16S rRNA gene sequence analysis both strains
      E20 and E50(T) are affiliated with the genus Cellvibrio, sharing the highest
      similarity with Cellvibrio gandavensis LMG 18551(T) (96.4%) and (97.1%),
      respectively. Strains E20 and E50(T) were oxidase and catalase-positive, grew at
      a temperature range between 16 and 37  degrees C and in the presence of 0-5% NaCl
      (w/v). The DNA G+C contents were 52.1 mol% (E20) and 51.6 mol% (E50(T)). Major
      fatty acids of strains E20 and E50(T) were summed feature 3 (C16 : 1omega7c
      and/or iso-C(15 : 0) 2-OH), C(16 : 0), C(18 : 1)omega7c, C(12 : 0), C(18 : 0) and
      C(12 : 0) 3-OH. The DNA-DNA relatedness of the strains to Cellvibrio gandavensis
      LMG 18551(T) was 39% for strain E20 and 58% for strain E50(T). The nitrogen
      fixation capability of strains E20 and E50(T) was confirmed by the acetylene
      reduction assay. On the basis of our polyphasic taxonomic study, strains E20 and
      E50(T) represent a novel species of the genus Cellvibrio, for which the name
      Cellvibrio diazotrophicus is proposed. The type strain of Cellvibrio
      diazotrophicus is E50(T) ( = LMG 27267(T) = KACC 17069(T)). An emended
      description of the genus Cellvibrio is proposed based on the capability of fixing
      nitrogen and growth in presence of up to 5% NaCl (w/v).

PMID- 24105944
TI  - Marinomonas fungiae sp. nov., isolated from the coral Fungia echinata from the
      Andaman Sea.
AB  - A novel aerobic marine bacterium, strain AN44(T), was isolated from the coral
      Fungia echinata sampled from the Andaman Sea, India. Cells were Gram-negative,
      motile and rod-shaped. Oxidase and catalase tests were positive. Heterotrophic
      growth was observed at pH 5.5-10 and at 16-42  degrees C, with optimum growth at
      pH 7-8 and 28  degrees C. Strain AN44(T) grew in the presence of 0.5-11% (w/v)
      NaCl; the optimal NaCl concentration for growth was 3-5%. The DNA G+C content was
      47.8 mol%. Predominant cellular fatty acids of strain AN44(T) were C(18 :
      1)omega7c, C(16 : 1)omega7c/C(16 : 1)omega6c, C(16 : 0), C(10 : 0) 3-OH, C(12 :
      0), C(10 : 0), C(14 : 0) and C(18 : 0). The sole isoprenoid ubiquinone was Q-8.
      The polar lipids were an unidentified phospholipid, an unidentified
      aminophospholipid and two unidentified glycolipids. 16S rRNA gene sequence
      comparisons revealed that strain AN44(T) clustered within the radiation of the
      genus Marinomonas and showed similarity of 97.9% with Marinomonas ostreistagni
      UST010306-043(T), 97.8% with Marinomonas aquimarina 11SM4(T), 97.1% with
      Marinomonas brasilensis R-40503(T) and 97.0% with Marinomonas communis 8(T).
      However, DNA-DNA relatedness between strain AN44(T) and closely related type
      strains was well below 70%. On the basis of the data from the present polyphasic
      taxonomic study, strain AN44(T) is considered to represent a novel species of the
      genus Marinomonas, for which the name Marinomonas fungiae sp. nov. is proposed.
      The type strain is AN44(T) ( = JCM 18476(T) = LMG 27065(T)).

PMID- 24105945
TI  - Diaphorobacter aerolatus sp. nov., isolated from air, and emended description of
      the genus Diaphorobacter.
AB  - A Gram-stain-negative, non-motile, aerobic rod, designated 8604S-37(T), was
      isolated from an outdoor air sample collected in Suwon region, Republic of Korea.
      The isolate was catalase-positive and oxidase-negative. 16S rRNA gene sequence
      analysis indicated that strain 8604S-37(T) was most closely related to
      Diaphorobacter nitroreducens NA10B(T) and Diaphorobacter oryzae RF3(T), with
      which it shared 97.0% 16S rRNA gene sequence similarity. Strain 8604S-37(T) grew
      at 10-37  degrees C (optimum 28  degrees C; no growth occurred at 4 or 40 
      degrees C) and pH 5-9 (optimum pH 7). The strain tolerated up to 3% NaCl (w/v)
      (optimum 0%). The only respiratory quinone was ubiquinone-8 (Q-8). The polar
      lipid profile comprised phosphatidylethanolamine, phosphatidylglycerol,
      diphosphatidylglycerol and one unknown aminolipid. The major fatty acids were C16
      : 0, summed feature 3 (comprising C(16 : 1)omega7c and/or iso-C(15 : 0) 2-OH),
      summed feature 8 (C(18 : 1)omega6c and/or C(18 : 1)omega7c) and C(17 : 0) cyclo,
      and the predominant hydroxy fatty acid was C(10 : 0) 3-OH. Strain 8604S-37(T)
      exhibited less than 50% DNA-DNA relatedness with Diaphorobacter nitroreducens
      KACC 13856(T) and Diaphorobacter oryzae KACC 16857(T). The DNA G+C content was 65
      mol%. Strain 8604S-37(T) represents a novel species of the genus Diaphorobacter,
      for which the name Diaphorobacter aerolatus sp. nov. is proposed. The type strain
      is 8604S-37(T) ( = KACC 16536(T) = NBRC 108926(T)). An emended description of the
      genus Diaphorobacter is also proposed.

PMID- 24105946
TI  - Brevibacillus fulvus sp. nov., isolated from a compost pile.
AB  - Two strains, designated K2814(T) and K282, were isolated from a compost pile in
      Japan. These strains were Gram-stain-variable, aerobic, motile and endospore
      forming rods. The strains produced a characteristic brown non-diffusible pigment.
      The 16S rRNA gene sequences of the strains were 100% identical and had high
      similarity to that of Brevibacillus levickii LMG 22481(T) (97.3%). Phylogenetic
      analyses based on 16S rRNA gene sequences revealed that these strains belong to
      the genus Brevibacillus. Strains K2814(T) and K282 contained meso-diaminopimelic
      acid in their cell walls. Strains K2814(T) and K282 contained MK-7 (96.0 and
      97.2%, respectively) and MK-8 (4.0 and 2.8%, respectively) as the major and minor
      menaquinones, respectively. Their major cellular fatty acids were anteiso-C(15 :
      0), anteiso-C(17 : 0), iso-C(15 : 0) and iso-C(17 : 0). The DNA G+C contents of
      strains K2814(T) and K282 were 48.8 and 49.8 mol%, respectively. Polar lipids of
      strain K2814(T) were composed of phosphatidyl-N-methylethanolamine,
      phosphatidylglycerol, diphosphatidylglycerol, phosphatidylethanolamine, an
      unidentified phospholipid, three unidentified polar lipids, an unidentified
      aminophospholipid and an unidentified aminolipid. The level of DNA-DNA
      relatedness between strains K2814(T) and K282 was 99 or 100%, and levels between
      strain K2814(T) and the type strains of seven related species of the genus
      Brevibacillus, including Brevibacillus levickii LMG 22481(T), were below 59%.
      From the chemotaxonomic and physiological data and the levels of DNA-DNA
      relatedness, these two strains should be classified as representing a novel
      species of the genus Brevibacillus, for which the name Brevibacillus fulvus sp.
      nov. (type strain K2814(T) = JCM 18162(T) = ATCC BAA-2417(T) = DSM 25523(T)) is
      proposed.

PMID- 24105949
TI  - Changes in the structure and function of northern Alaskan ecosystems when
      considering variable leaf-out times across groupings of species in a dynamic
      vegetation model.
AB  - The phenology of arctic ecosystems is driven primarily by abiotic forces, with
      temperature acting as the main determinant of growing season onset and leaf
      budburst in the spring. However, while the plant species in arctic ecosystems
      require differing amounts of accumulated heat for leaf-out, dynamic vegetation
      models simulated over regional to global scales typically assume some average
      leaf-out for all of the species within an ecosystem. Here, we make use of air
      temperature records and observations of spring leaf phenology collected across
      dominant groupings of species (dwarf birch shrubs, willow shrubs, other deciduous
      shrubs, grasses, sedges, and forbs) in arctic and boreal ecosystems in Alaska. We
      then parameterize a dynamic vegetation model based on these data for four types
      of tundra ecosystems (heath tundra, shrub tundra, wet sedge tundra, and tussock
      tundra), as well as ecotonal boreal white spruce forest, and perform model
      simulations for the years 1970-2100. Over the course of the model simulations, we
      found changes in ecosystem composition under this new phenology algorithm
      compared with simulations with the previous phenology algorithm. These changes
      were the result of the differential timing of leaf-out, as well as the ability
      for the groupings of species to compete for nitrogen and light availability.
      Regionally, there were differences in the trends of the carbon pools and fluxes
      between the new phenology algorithm and the previous phenology algorithm,
      although these differences depended on the future climate scenario. These
      findings indicate the importance of leaf phenology data collection by species and
      across the various ecosystem types within the highly heterogeneous Arctic
      landscape, and that dynamic vegetation models should consider variation in leaf
      out by groupings of species within these ecosystems to make more accurate
      projections of future plant distributions and carbon cycling in Arctic regions. 

PMID- 24105947
TI  - Focus issue: calcium signaling.

PMID- 24105950
TI  - Clinical diagnosis of propriospinal myoclonus is unreliable: an
      electrophysiologic study.
AB  - Propriospinal myoclonus is a rare movement disorder that is hypothesized to arise
      from a spinal generator that transmits activity up and down the spinal cord via
      long propriospinal pathways. Polymyography is mandatory for the diagnosis, but
      the typical electrophysiological pattern described for propriospinal myoclonus
      has been also found in patients with psychogenic axial jerks, supported by the
      presence of a Bereitschaftspotential (BP; from German, "readiness potential,"
      also called the premotor potential). We evaluated polymyographic findings in 65
      patients referred to us with a clinical diagnosis of propriospinal myoclonus and
      also looked for the presence of the BP, as detected by jerk-locked back
      averaging. At clinical reassessment by a movement disorder specialist, nearly one
      half of the patients had clinical clues suggestive of a psychogenic cause of the
      jerks. Electrophysiological studies were carried out on all 65 patients.
      Polymyography findings revealed an incongruent electromyographic pattern for
      propriospinal myoclonus in 84.6% of patients and the presence of the BP in 86.1%
      of the entire cohort. When taking into account either the presence of BP and/or
      incongruence of polymyographic features, all patients, including the
      approximately 50% clinically diagnosed as organic propriospinal myoclonus by a
      movement disorder expert, had strong neurophysiological evidence for a
      psychogenic origin of their jerks. The clinical distinction of propriospinal
      myoclonus from psychogenic axial jerks is unreliable. This is the largest cohort
      of patients with axial jerks reported so far and we suggest that most of the
      patients with a clinical picture that clinically resembles propriospinal
      myoclonus are likely to be psychogenic.

PMID- 24105951
TI  - From sediment to tissue and tissue to sediment: an evaluation of statistical
      bioaccumulation models.
AB  - Biota-sediment accumulation factors (BSAFs) and biota-sediment accumulation
      regressions (BSARs) are statistical models that may be used to estimate tissue
      chemical concentrations from sediment chemical concentrations or vice versa.
      Biota-sediment accumulation factors and BSARs are used to fill tissue
      concentration data gaps, set sediment preliminary remediation goals (PRGs), and
      make projections about the effectiveness of potential sediment cleanup projects
      in reducing tissue chemical concentrations. We explored field-based, benthic
      invertebrate biota-sediment chemical concentration relationships using data from
      the US Environmental Protection Agency (USEPA) Mid-Continent Ecology Division
      (MED) BSAF database. Approximately two thirds of the 262 relationships
      investigated were very poor (r(2)  < 0.3 or p-value >= 0.05); for some of the
      biota-sediment relationships that did have a significant nonzero slope (p-value <
      0.05), lipid-normalized tissue concentrations tended to decrease as the colocated
      organic carbon (OC)-normalized sediment concentration increased. Biota-sediment
      relationships were further evaluated for 3 of the 262 datasets. Biota-sediment
      accumulation factors, linear regressions, model II regressions, illustrative
      sediment PRGs, and confidence intervals (CIs) were calculated for each of the
      three examples. These examples illustrate some basic but important statistical
      practices that should be followed before selecting a BSAR or BSAF or relying on
      these simple models of biota-sediment relationships to support consequential
      management decisions. These practices include the following: one should not
      assume that the relationship between chemical concentrations in tissue and
      sediment is necessarily linear, one should not assume the model intercept to be
      zero, and one should not place too much stock on models that are heavily
      influenced by one or a few high chemical concentration data points. People will
      continue to use statistical models of field-based biota-sediment chemical
      concentration relationships to support sediment investigations and remedial
      action decisions. However, it should not be assumed that the models will be
      reliable. In developing and applying BSAFs and BSARs, it is essential that best
      practices are followed and model limitations and uncertainties are understood,
      acknowledged, and quantified as much as possible.

PMID- 24105952
TI  - The toll-like receptor 3 ligand, poly(I:C), improves immunosuppressive function
      and therapeutic effect of mesenchymal stem cells on sepsis via inhibiting MiR
      143.
AB  - Mesenchymal stem cells (MSCs) are attractive candidates for clinical therapeutic
      applications. Recent studies indicate MSCs express active Toll-like receptors
      (TLRs), but their effect on MSCs and the underlying mechanisms remain unclear. In
      this study, we found that, after treating human umbilical cord MSCs with various
      TLR ligands, only TLR3 ligand, poly(I:C), could significantly increase the
      expression of cyclooxygenase-2 (COX-2). Furthermore, poly(I:C) could enhance
      MSCs' anti-inflammatory effect on macrophages. Next, we focused on the regulatory
      roles of microRNAs (miRNAs) in the process of poly(I:C) activating MSCs. Our
      experiments indicated that miR-143 expression was significantly decreased in MSCs
      with poly(I:C) treatment, and the expression level of miR-143 could regulate the
      effect of poly(I:C) on MSCs' immunosuppressive function. Subsequent results
      showed that the reporter genes with putative miR-143 binding sites from the
      transforming growth factor-beta-activated kinase-1 (TAK1) and COX-2 3'
      untranslated regions were downregulated in the presence of miR-143. In addition,
      mRNA and protein expression of TAK1 and COX-2 in MSCs was also downregulated with
      miR-143 overexpression, suggesting that TAK1 and COX-2 are target genes of miR
      143 in MSCs. Consistent with miR-143 overexpression, TAK1 interference also
      attenuated MSCs' immunosuppressive function enhanced by poly(I:C). Additionally,
      it was shown that TLR3-activated MSCs could improve survival in cecal ligation
      and puncture (CLP)-induced sepsis, while miR-143 overexpression reduced the
      effectiveness of this therapy. These results proved that poly(I:C) improved the
      immunosuppressive abilities of MSCs, revealed the regulatory role of miRNAs in
      the process, and may provide an opportunity for potential novel therapies for
      sepsis.

PMID- 24105953
TI  - Macromolecular prodrugs for controlled delivery of ribavirin.
AB  - Ribavirin (RBV)-containing polymers are synthesized based on poly(N
      vinylpyrrolidone) and poly(acrylic acid), two polymers with extensive
      characterization in biomedicine. The copolymers are shown to exhibit a minor to
      negligible degree of association with erythrocytes, thus effectively eliminating
      the origin of the main side effects of RBV. The therapeutic benefit of
      macromolecular RBV prodrugs is illustrated by matched efficacy in suppressing
      production of nitric oxide by stimulated cultured macrophages as compared to
      pristine RBV with no associated cytotoxicity, which is in stark contrast to an
      RBV-based treatment which results in a significant decrease in cell viability.
      These results contribute to the development of antiviral polymer therapeutics and
      delivery of RBV in particular. 

PMID- 24105954
TI  - SHATI/NAT8L regulates neurite outgrowth via microtubule stabilization.
AB  - We previously identified a new molecule, "SHATI/NAT8L," which has an inhibitory
      effect on methamphetamine (METH)-induced hyperlocomotion, sensitization, and
      conditioned place preference. Nevertheless, the extent of SHATI localization and
      its functions are only partially understood. In this study, we used the FLAG-tag
      method to investigate SHATI localization. We found that SHATI was localized to
      microtubules when expressed in COS7 cells and cortical primary neurons. This
      distribution of SHATI was less apparent after cells were treated with colchicine,
      a tubulin polymerization inhibitor that disrupts the microtubule structure. This
      finding suggests that SHATI is associated with microtubule structure.
      Interestingly, overexpression of SHATI in COS7 cells could attenuate the
      colchicine-induced decrease in acetylated microtubules, indicating that SHATI
      plays a role in stabilizing microtubules. Furthermore, we showed that Shati
      deletion impaired neurite elongation. In cortical primary neurons, neurite length
      and complexity in Shati-knockout (KO) mice were significantly decreased. In
      pyramidal neurons in the prefrontal cortex, dendrite length and complexity were
      also significantly decreased in Shati-KO mice compared with wild-type mice. These
      results suggest a novel function for SHATI, which may be a new member of the
      microtubule-associated protein family.

PMID- 24105955
TI  - Phenylethenyl-substituted triphenylamines: efficient, easily obtainable, and
      inexpensive hole-transporting materials.
AB  - Star-shaped charge-transporting materials with a triphenylamine (TPA) core and
      various phenylethenyl side arm(s) were obtained in a one-step synthetic procedure
      from commercially available and relatively inexpensive starting materials.
      Crystallinity, glass-transition temperature, size of the pi-conjugated system,
      energy levels, and the way molecules pack in the solid state can be significantly
      influenced by variation of the structure of these side arm(s). An increase in the
      number of phenylethenyl side arms was found to hinder intramolecular motions of
      the TPA core, and thereby provide significant enhancement of the fluorescence
      quantum yield of the TPA derivatives in solution. On the other hand, a larger
      number of side arms facilitated exciton migration through the dense side-arm
      network formed in the solid state and, thus, considerably reduces fluorescence
      efficiency by migration-assisted nonradiative relaxation. This dense network
      enables charges to move more rapidly through the hole-transport material layer,
      which results in very good charge drift mobility (MU up to 0.017 cm(2) V (-1) s(
      1)).

PMID- 24105956
TI  - Evidence for an oxygen anthracene sandwich complex.

PMID- 24105957
TI  - Evaluation of in vivo genotoxicity induced by N-ethyl-N-nitrosourea,
      benzo[a]pyrene, and 4-nitroquinoline-1-oxide in the Pig-a and gpt assays.
AB  - The recently developed Pig-a mutation assay is based on flow cytometric
      enumeration of glycosylphosphatidylinositol (GPI) anchor-deficient red blood
      cells caused by a forward mutation in the Pig-a gene. Because the assay can be
      conducted in nontransgenic animals and the mutations accumulate with repeat
      dosing, we believe that the Pig-a assay could be integrated into repeat-dose
      toxicology studies and provides an alternative to transgenic rodent (TGR)
      mutation assays. The capacity and characteristics of the Pig-a assay relative to
      TGR mutation assays, however, are unclear. Here, using transgenic gpt delta mice,
      we compared the in vivo genotoxicity of single oral doses of N-ethyl-N
      nitrosourea (ENU, 40 mg/kg), benzo[a]pyrene (BP, 100 and 200 mg/kg), and 4
      nitroquinoline-1-oxide (4NQO, 50 mg/kg) in the Pig-a (peripheral blood) and gpt
      (bone marrow and liver) gene mutation assays. Pig-a assays were conducted at 2,
      4, and 7 weeks after the treatment, while gpt assays were conducted on tissues
      collected at the 7-week terminal sacrifice. ENU increased both Pig-a and gpt
      mutant frequencies (MFs) at all sampling times, and BP increased MFs in both
      assays but the Pig-a MFs peaked at 2 weeks and then decreased. Although 4NQO
      increased gpt MFs in the liver, only weak, nonsignificant increases (two- or
      threefold above control) were detected in the bone marrow in both the Pig-a and
      the gpt assay. These findings suggest that further studies are needed to
      elucidate the kinetics of the Pig-a mutation assay in order to use it as an
      alternative to the TGR mutation assay.

PMID- 24105958
TI  - The profiling and identification of the metabolites of (+)-catechin and study on
      their distribution in rats by HPLC-DAD-ESI-IT-TOF-MS(n) technique.
AB  - (+)-Catechin, a potential beneficial compound to human health, is widely
      distributed in plants and foods. A high-performance liquid chromatography with
      diode array detector and combined with electrospray ionization ion trap time-of
      flight multistage mass spectrometry method was applied to profile and identify
      the metabolites of (+)-catechin in rats and to study the distribution of these
      metabolites in rat organs for the first time. In total, 51 phase II metabolites
      (44 new) and three phase I metabolites were tentatively identified, comprising 16
      (+)-catechin conjugates, 14 diarylpropan-2-ol metabolites, 6 phenyl valerolactone
      metabolites and 18 aromatic acid metabolites. Further, 19 phase II metabolites
      were new compounds. The in vivo metabolic reactions of (+)-catechin in rats were
      found to be ring-cleavage, sulfation, glucuronidation, methylation,
      dehydroxylation and dehydrogenation. The numbers of detected metabolites in
      urine, plasma, small intestine, kidney, liver, lung, heart, brain and spleen were
      53, 23, 27, 9, 7, 5, 3, 2 and 1, respectively. This indicated that small
      intestine, kidney and liver were the major organs for the distribution of (+)
      catechin metabolites. In addition, eight metabolites were found to possess
      bioactivities according to literature. These results are very helpful for better
      comprehension of the in vivo metabolism of (+)-catechin and its pharmacological
      actions, and also can give strong indications on the effective forms of (+)
      catechin in vivo.

PMID- 24105959
TI  - Nanoparticle-driven orientation transition and soft-shear alignment in diblock
      copolymer films via dynamic thermal gradient field.
AB  - Sharp dynamic thermal gradient (?T ~ 45  degrees C mm(-1)) field-driven assembly
      of cylinder-forming block copolymer (c-BCP) films filled with PS-coated gold
      nanoparticles (AuNPs; dNP ~ 3.6 nm, phiNP ~ 0-0.1) is studied. The influence of
      increasing AuNP loading fraction on dispersion and assembly of AuNPs within c-BCP
      (PS-PMMA) films is investigated via both static and dynamic thermal gradient
      fields. With phiNP increasing, a sharp transition from vertical to random in
      plane horizontal cylinder orientation is observed due to enrichment of AuNPs at
      the substrate side and favorable interaction of PMMA chains with gold cores.
      Furthermore, a detachable capping elastomer layer can self-align these random
      oriented PMMA microdomains into unidirectional hybrid AuNP/c-BCP nanolines,
      quantified with an alignment order parameter, S.

PMID- 24105960
TI  - Endogenous versus exogenous growth factor regulation of articular chondrocytes.
AB  - Anabolic growth factors that regulate the function of articular chondrocytes are
      candidates for articular cartilage repair. Such factors may be delivered by
      pharmacotherapy in the form of exogenous proteins, or by gene therapy as
      endogenous proteins. It is unknown whether delivery method influences growth
      factor effectiveness in regulating articular chondrocyte reparative functions. We
      treated adult bovine articular chondrocytes with exogenous recombinant insulin
      like growth factor-I (IGF-I) and transforming growth factor-beta1 (TGF-beta1), or
      with the genes encoding these growth factors for endogenous production. Treatment
      effects were measured as change in chondrocyte DNA content, glycosaminoglycan
      production, and aggrecan gene expression. We found that IGF-I stimulated
      chondrocyte biosynthesis similarly when delivered by either exogenous or
      endogenous means. In contrast, exogenous TGF-beta1 stimulated these reparative
      functions, while endogenous TGF-beta1 had little effect. Endogenous TGF-beta1
      became more bioactive following activation of the transgene protein product.
      These data indicate that effective mechanisms of growth factor delivery for
      articular cartilage repair may differ for different growth factors. In the case
      of IGF-I, gene therapy or protein therapy appear to be viable options. In
      contrast, TGF-beta1 gene therapy may be constrained by a limited ability of
      chondrocytes to convert latent complexes to an active form.

PMID- 24105961
TI  - Characterization of Ile-His-Arg-Phe, a novel rice-derived vasorelaxing peptide
      with hypotensive and anorexigenic activities.
AB  - SCOPE: Recently, we found that dipeptide Arg-Phe (RF) had cholecystokinin (CCK)
      dependent vasorelaxing activity. The RF sequence is often observed in the primary
      structure of natural food proteins. In the current study, we investigated
      enzymatic conditions for the release of RF-related peptides from rice glutelin, a
      major storage protein, using gastrointestinal proteases. RF-related peptides were
      then characterized. METHODS AND RESULTS: It was found that RF and Ile-His-Arg-Phe
      (IHRF) were released in the chymotrypsin digest of the partial structure of rice
      glutelin. We then focused on previously unidentified IHRF, corresponding to rice
      glutelin(155-158). IHRF had vasorelaxing activity in the mesenteric artery of
      spontaneous hypertensive rats (SHRs). Orally administered IHRF lowered systolic
      blood pressure in SHRs. The antihypertensive activity of IHRF was more potent and
      long-lasting than that of RF. IHRF-induced vasorelaxing activity was not blocked
      by inhibitors of nitric oxide synthase and cyclooxygenase, but by an antagonist
      for CCK1 receptor. IHRF also had CCK-like suppressive activities in food intake
      and gastrointestinal transit. IHRF increased intracellular Ca2+ flux and CCK
      release in the enteroendocrine cell STC-1. CONCLUSION: IHRF, a novel CCK
      dependent vasorelaxing peptide, decreases both blood pressure and food intake in
      rodents.

PMID- 24105962
TI  - Using acoustic technology to reduce bark beetle reproduction.
AB  - BACKGROUND: Acoustic signals play a critical role in mate choice, species
      recognition, communication, territoriality, predator escape and prey selection.
      Bark beetles, which are significant disturbance agents of forests, produce a
      variety of acoustic signals. RESULTS: A bioacoustic approach to reducing bark
      beetle reproduction within wood tissues was explored. Playback of modified
      biological sounds reduced beetle reproductive output, tunneling distance and
      adult survival. CONCLUSION: The targeted use of biologically relevant sounds
      disrupts insect behaviors and could be a species-specific, environmentally
      friendly method of insect management.

PMID- 24105963
TI  - A brief understanding of process optimisation in microwave-assisted extraction of
      botanical materials: options and opportunities with chemometric tools.
AB  - INTRODUCTION: Extraction forms the very basic step in research on natural
      products for drug discovery. A poorly optimised and planned extraction
      methodology can jeopardise the entire mission. OBJECTIVE: To provide a vivid
      picture of different chemometric tools and planning for process optimisation and
      method development in extraction of botanical material, with emphasis on
      microwave-assisted extraction (MAE) of botanical material. METHODS: A review of
      studies involving the application of chemometric tools in combination with MAE of
      botanical materials was undertaken in order to discover what the significant
      extraction factors were. Optimising a response by fine-tuning those factors,
      experimental design or statistical design of experiment (DoE), which is a core
      area of study in chemometrics, was then used for statistical analysis and
      interpretations. RESULTS: In this review a brief explanation of the different
      aspects and methodologies related to MAE of botanical materials that were
      subjected to experimental design, along with some general chemometric tools and
      the steps involved in the practice of MAE, are presented. A detailed study on
      various factors and responses involved in the optimisation is also presented.
      CONCLUSION: This article will assist in obtaining a better insight into the
      chemometric strategies of process optimisation and method development, which will
      in turn improve the decision-making process in selecting influential extraction
      parameters.

PMID- 24105964
TI  - Dimensional matching of polycyclic aromatics with rectangular metallacycles:
      insertion modes determined by [C-H...pi] interactions.
AB  - A family of Pd(II)/Pt(II) dinuclear receptors, designed to give a smooth increase
      in their cavity lengths (from 7.46-13.78 A), is presented. Their inclusion
      complexes with a representative set of polycyclic aromatic substrates
      (naphthalene, carbazol, pyrene, and benzo[a]pyrene), were characterized and
      studied in aqueous solution and the solid state. By taking into account the
      dimensions of both receptors and substrates, an excellent complementarity was
      found between the size of the receptors and their ability to complex a given
      substrate. Furthermore, this dimensional matching results in specific binding
      modes depending on the ability of the guest to establish stabilizing [C-H...pi]
      interactions with the host.

PMID- 24105965
TI  - HomoSAR: bridging comparative protein modeling with quantitative structural
      activity relationship to design new peptides.
AB  - Peptides play significant roles in the biological world. To optimize activity for
      a specific therapeutic target, peptide library synthesis is inevitable; which is
      a time consuming and expensive. Computational approaches provide a promising way
      to simply elucidate the structural basis in the design of new peptides. Earlier,
      we proposed a novel methodology termed HomoSAR to gain insight into the structure
      activity relationships underlying peptides. Based on an integrated approach,
      HomoSAR uses the principles of homology modeling in conjunction with the
      quantitative structural activity relationship formalism to predict and design new
      peptide sequences with the optimum activity. In the present study, we establish
      that the HomoSAR methodology can be universally applied to all classes of
      peptides irrespective of sequence length by studying HomoSAR on three peptide
      datasets viz., angiotensin-converting enzyme inhibitory peptides, CAMEL-s
      antibiotic peptides, and hAmphiphysin-1 SH3 domain binding peptides, using a set
      of descriptors related to the hydrophobic, steric, and electronic properties of
      the 20 natural amino acids. Models generated for all three datasets have
      statistically significant correlation coefficients (r(2)) and predictive r2
      (r(pred)2) and cross validated coefficient ( q(LOO)2). The daintiness of this
      technique lies in its simplicity and ability to extract all the information
      contained in the peptides to elucidate the underlying structure activity
      relationships. The difficulties of correlating both sequence diversity and
      variation in length of the peptides with their biological activity can be
      addressed. The study has been able to identify the preferred or detrimental
      nature of amino acids at specific positions in the peptide sequences.

PMID- 24105966
TI  - Real-time amyloid aggregation monitoring with a photonic crystal-based approach.
AB  - We propose the application of a new label-free optical technique based on
      photonic nanostructures to real-time monitor the amyloid-beta 1-42 (Abeta(1-42))
      fibrillization, including the early stages of the aggregation process, which are
      related to the onset of the Alzheimer's Disease (AD). The aggregation of Abeta
      peptides into amyloid fibrils has commonly been associated with neuronal death,
      which culminates in the clinical features of the incurable degenerative AD.
      Recent studies revealed that cell toxicity is determined by the formation of
      soluble oligomeric forms of Abeta peptides in the early stages of aggregation. At
      this phase, classical amyloid detection techniques lack in sensitivity. Upon a
      chemical passivation of the sensing surface by means of polyethylene glycol, the
      proposed approach allows an accurate, real-time monitoring of the refractive
      index variation of the solution, wherein Abeta(1-42) peptides are aggregating.
      This measurement is directly related to the aggregation state of the peptide
      throughout oligomerization and subsequent fibrillization. Our findings open new
      perspectives in the understanding of the dynamics of amyloid formation, and
      validate this approach as a new and powerful method to screen aggregation at
      early stages. 

PMID- 24105967
TI  - Measurement error in epidemiologic studies of air pollution based on land-use
      regression models.
AB  - Land-use regression (LUR) models are increasingly used to estimate air pollution
      exposure in epidemiologic studies. These models use air pollution measurements
      taken at a small set of locations and modeling based on geographical covariates
      for which data are available at all study participant locations. The process of
      LUR model development commonly includes a variable selection procedure. When LUR
      model predictions are used as explanatory variables in a model for a health
      outcome, measurement error can lead to bias of the regression coefficients and to
      inflation of their variance. In previous studies dealing with spatial predictions
      of air pollution, bias was shown to be small while most of the effect of
      measurement error was on the variance. In this study, we show that in realistic
      cases where LUR models are applied to health data, bias in health-effect
      estimates can be substantial. This bias depends on the number of air pollution
      measurement sites, the number of available predictors for model selection, and
      the amount of explainable variability in the true exposure. These results should
      be taken into account when interpreting health effects from studies that used LUR
      models. 

PMID- 24105968
TI  - Persistent figure-eight and side-to-side head shaking is a marker for
      rhombencephalosynapsis.
AB  - BACKGROUND: Head-shaking stereotypies have been described in patients with
      neurological impairment. We noted an unusual preponderance of head shaking in
      patients with rhombencephalosynapsis (RES). We sought to delineate the movements
      further and determine whether oculomotor and vestibular testing could reveal
      their cause. METHODS: Information was collected from direct observation, video
      review and parental questionnaire from 59 patients with RES. Oculomotor and
      vestibular testing was performed in 4 children. RESULTS: Of 59 patients, 50 had
      persistent head shaking that was often observed years before RES was recognized.
      Three affected children demonstrated abnormal central vestibular processing.
      CONCLUSIONS: Head-shaking is common in RES. These characteristic movements may
      provide input to a defective vestibular system or may represent a motor pattern
      that is usually suppressed by vestibular feedback. Persistent head shaking should
      alert clinicians to the possible presence of a congenital hindbrain abnormality
      that affects the vestibulocerebellum, particularly RES.

PMID- 24105969
TI  - Pediatric glaucoma terminology.
AB  - Glaucoma is a term that refers to many different disorders which may be
      characterized by age of onset, associated ocular findings, or associated systemic
      malformations and diseases. Specification of the type of glaucoma, both
      clinically, and where applicable, molecularly aids in diagnosis, counseling,
      treatment, and prognosis. The objective of this report is to assist geneticists
      in understanding glaucoma and recognizing the importance of detailed terminology
      in clinical genetic diagnosis.

PMID- 24105970
TI  - A {Cr(III)2Dy(III)2} single-molecule magnet: enhancing the blocking temperature
      through 3d magnetic exchange.

PMID- 24105971
TI  - Drought footprint on European ecosystems between 1999 and 2010 assessed by
      remotely sensed vegetation phenology and productivity.
AB  - Drought affects more people than any other natural disaster but there is little
      understanding of how ecosystems react to droughts. This study jointly analyzed
      spatio-temporal changes of drought patterns with vegetation phenology and
      productivity changes between 1999 and 2010 in major European bioclimatic zones.
      The Standardized Precipitation and Evapotranspiration Index (SPEI) was used as
      drought indicator whereas changes in growing season length and vegetation
      productivity were assessed using remote sensing time-series of Normalized
      Difference Vegetation Index (NDVI). Drought spatio-temporal variability was
      analyzed using a Principal Component Analysis, leading to the identification of
      four major drought events between 1999 and 2010 in Europe. Correspondence
      Analysis showed that at the continental scale the productivity and phenology
      reacted differently to the identified drought events depending on ecosystem and
      land cover. Northern and Mediterranean ecosystems proved to be more resilient to
      droughts in terms of vegetation phenology and productivity developments. Western
      Atlantic regions and Eastern Europe showed strong agglomerations of decreased
      productivity and shorter vegetation growing season length, indicating that these
      ecosystems did not buffer the effects of drought well. In a climate change
      perspective, increase in drought frequency or intensity may result in larger
      impacts over these ecosystems, thus management and adaptation strategies should
      be strengthened in these areas of concerns.

PMID- 24105972
TI  - Tunable spin-crossover behavior of the Hofmann-like network {Fe(bpac)[Pt(CN)4]}
      through host-guest chemistry.
AB  - A study of the spin-crossover (SCO) behavior of the tridimensional porous
      coordination polymer {Fe(bpac)[Pt(CN)4]} (bpac=bis(4-pyridyl)acetylene) on
      adsorption of different mono- and polyhalobenzene guest molecules is presented.
      The resolution of the crystal structure of {Fe(bpac)[Pt(CN)4]}?G (G=1,2,4
      trichlorobenzene) shows preferential guest sites establishing pi???pi stacking
      interactions with the host framework. These host-guest interactions may explain
      the relationship between the modification of the SCO behavior and both the
      chemical nature of the guest molecule (electronic factors) and the number of
      adsorbed molecules (steric factors).

PMID- 24105973
TI  - Enhanced stem cell pluripotency in surface-modified electrospun fibrous matrices.
AB  - A previously screened "hit chemistry" (N-[3-(dimethylamino)propyl]
      methacrylamide) that supports strong attachment and long-term self-renewal of ES
      cells is selected and grafted to poly(ether sulfone) (PES) fibrous matrices
      through plasma-induced graft polymerization. The 3D modified fibers exhibit
      higher cell proliferation and greater expression of pluripotency markers of mouse
      ES cells than 2D membranes. It is the first demonstration of scaling up an
      optimal synthetic surface chemistry in 2D using a high throughput synthesis,
      screening, and selection method to 3D that strongly influences pluripotent stem
      cell growth. 

PMID- 24105974
TI  - Challenges faced by key informants practicing case finding for vision loss in
      children: the experience in Cross River State, Nigeria.
AB  - BACKGROUND: To identify challenges faced by key informants (KIs) in a childhood
      blindness and severe visual impairment survey in Cross River State (CRS),
      Nigeria. METHODS: Based on eligibility 742 KIs were selected by their
      village/clan heads in the 18 local government areas (LGAs) of Cross River State.
      After training in each LGA, KIs were to identify children with visual problems.
      KIs used a number of methods to identify children with vision loss. After the
      case detection period, KIs were requested to bring children suspected of vision
      problems to a central site for examination. Following this, an interviewer
      administered semi-structured interview was used to obtain information from the
      KIs. Thematic content analysis was used to identify these challenges. RESULTS:
      Among the 742 KIs, 642 did not provide any comment on challenges during
      interview; 100 KIs reported challenges. Major challenge themes identified were
      issues related to the family of the child and issues related to operational
      conditions, principally transportation, communication, and incentives.
      CONCLUSIONS: It is likely that challenges were under-reported. Research is needed
      to understand why some parents feel stigmatized by having children with vision
      problems. Community based programmes need to strengthen community awareness,
      address trust issues, and ensure transportation and communication are improved in
      order to enhance programme success.

PMID- 24105975
TI  - Magnetic quantum dots in biotechnology--synthesis and applications.
AB  - Quantum dots (QDs) have great promise in biological imaging, and as this promise
      is realized, there has been increasing interest in combining the benefits of QDs
      with those of other materials to yield composites with multifunctional
      properties. One of the most common materials combined with QDs is magnetic
      materials, either as ions (e.g. gadolinium) or as nanoparticles (e.g.
      superparamagnetic iron oxide nanoparticles, SPIONs). The fluorescent property of
      the QDs permits visualization, whereas the magnetic property of the composite
      enables imaging, magnetic separation, and may even have therapeutic benefit. In
      this review, the synthesis of fluorescent-magnetic nanoparticles, including
      magnetic QDs is explored; and the applications of these materials in imaging,
      separations, and theranostics are discussed. As the properties of these materials
      continue to improve, QDs have the potential to greatly impact biological imaging,
      diagnostics, and treatment. 

PMID- 24105976
TI  - Ambident reactivities of formaldehyde N,N-dialkylhydrazones.

PMID- 24105977
TI  - Valproic acid is a novel activator of AMP-activated protein kinase and decreases
      liver mass, hepatic fat accumulation, and serum glucose in obese mice.
AB  - Valproic acid (VPA) is a widely prescribed anticonvulsant for the treatment of
      epilepsy. Here we demonstrate that VPA is a novel activator of AMP-activated
      protein kinase (AMPK), a key regulator of cellular metabolism, using primary
      mouse and human hepatocytes. Incubation of primary mouse hepatocytes with VPA
      resulted in increased levels of phosphorylated AMPK and acetyl-CoA carboxylase
      (ACC). This finding was recapitulated using primary human hepatocytes.
      Pretreatment of mouse hepatocytes with a small-molecule inhibitor of AMPK,
      Compound C (6-[4-(2-piperidin-1-ylethoxy)phenyl]-3-pyridin-4-ylpyrazolo[1,5
      a]pyrimidine), abrogated the phosphorylation of ACC following treatment with VPA.
      The cytochrome P450 inhibitor 1-aminobenzotriazole blocked the VPA-stimulated
      phosphorylation of AMPK, suggesting a requirement for biotransformation of VPA.
      In line with this, treatment of hepatocytes with metabolites of VPA resulted in
      increased phosphorylation of AMPK/ACC as compared with VPA. Treatment of ob/ob
      mice with VPA for 14 days resulted in decreased liver masses, hepatic fat
      accumulation, and serum glucose. These results paralleled those observed in mice
      treated with metformin. In addition, a targeted mass spectrometry-based
      metabolomics assay revealed several small molecules that were differentially
      abundant in the serum of ob/ob mice treated with VPA as compared with vehicle
      treated mice. These studies are the first to establish VPA and its metabolites as
      in vitro activators of AMPK. 

PMID- 24105978
TI  - TIPS-tetracene- and TIPS-pentacene-annulated poly(norbornadiene)s: synthesis and
      properties.
AB  - The synthesis of tetracene- and pentacene-annulated norbornadienes, formed
      through the Diels-Alder reaction of a dehydroacene with cyclopentadiene is
      reported. Ring-opening metathesis polymerization (ROMP) leads to polymers that
      are investigated with respect to their physical, optical, and electronic
      properties by gel permeation chromatography (GPC), UV-vis spectroscopy, and
      cyclic voltammetry. The pentacene-containing polymer P1 is successfully
      integrated into an organic field-effect transistor (OFET); the tetracene
      containing polymer P2 is integrated into an organic light-emitting diode (OLED). 

PMID- 24105980
TI  - Infrared spectrum of the Si3H8+ cation: evidence for a bridged isomer with an
      asymmetric three-center two-electron Si-H-Si bond.
AB  - The IR spectrum of Si3H8(+) ions produced in a supersonic plasma molecular beam
      expansion of SiH4, He, and Ar is inferred from photodissociation of cold Si3H8(+)
      Ar complexes. Vibrational analysis of the spectrum is consistent with a Si3H8(+)
      structure (2(+)) obtained by a barrierless addition reaction of SiH4 to the
      disilene ion (H2Si=SiH2(+)) in the silane plasma. In this structure, one of the
      electronegative H atoms of SiH4 donates electron density into the partially
      filled electrophilic pi orbital of the disilene cation. The resulting asymmetric
      Si-H-Si bridge of the 2(+) isomer with a bond energy of approximately 60 kJ mol(
      1) is characteristic for a weak three-center two-electron bond, which is
      identified by its strongly IR active asymmetric Si-H-Si stretching fundamental at
      about 1765 cm(-1). The observed 2(+) isomer is calculated to be only a few kJ
      mol(-1) less stable than the global minimum structure of Si3H8(+) (1(+)), which
      is derived from vertical ionization of trisilane. Although more stable, 1(+) is
      not detected in the measured IR spectrum of Si3H8(+)-Ar, and its lower abundance
      in the supersonic plasma is rationalized by the production mechanism of Si3H8(+)
      in the silane plasma, in which a high barrier between 2(+) and 1(+) prevents the
      efficient formation of 1(+). The potential energy surface of Si3H8(+) is
      characterized in some detail by quantum chemical calculations. The structural,
      vibrational, electronic and energetic properties as well as the chemical bonding
      mechanism are investigated for a variety of low-energy Si3H8(+) isomers and their
      fragments. The weak intermolecular bonds of the Ar ligands in the Si3H8(+)-Ar
      isomers arise from dispersion and induction forces and induce only a minor
      perturbation of the bare Si3H8(+) ions. Comparison with the potential energy
      surface of C3H8(+) reveals the differences between the silicon and carbon
      species.

PMID- 24105979
TI  - Histone deacetylase inhibition with valproic acid downregulates osteocalcin gene
      expression in human dental pulp stem cells and osteoblasts: evidence for HDAC2
      involvement.
AB  - Adult mesenchymal stem cells, such as dental pulp stem cells, are of great
      interest for cell-based tissue engineering strategies because they can
      differentiate into a variety of tissue-specific cells, above all, into
      osteoblasts. In recent years, epigenetic studies on stem cells have indicated
      that specific histone alterations and modifying enzymes play essential roles in
      cell differentiation. However, although several studies have reported that
      valproic acid (VPA)-a selective inhibitor of histone deacetylases (HDAC)-enhances
      osteoblast differentiation, data on osteocalcin expression-a late-stage marker of
      differentiation-are limited. We therefore decided to study the effect of VPA on
      dental pulp stem cell differentiation. A low concentration of VPA did not reduce
      cell viability, proliferation, or cell cycle profile. However, it was sufficient
      to significantly enhance matrix mineralization by increasing osteopontin and bone
      sialoprotein expression. In contrast, osteocalcin levels were decreased, an
      effect induced at the transcriptional level, and were strongly correlated with
      inhibition of HDAC2. In fact, HDAC2 silencing with shRNA produced a similar
      effect to that of VPA treatment on the expression of osteoblast-related markers.
      We conclude that VPA does not induce terminal differentiation of osteoblasts, but
      stimulates the generation of less mature cells. Moreover, specific suppression of
      an individual HDAC by RNA interference could enhance only a single aspect of
      osteoblast differentiation, and thus produce selective effects.

PMID- 24105982
TI  - Reactivity change of cyclobutanols towards isocyanates: rhodium favors C
      carbamoylation over O-carbamoylation.

PMID- 24105981
TI  - Metabolomics and the search for biomarkers in Parkinson's disease.

PMID- 24105983
TI  - Image thresholding techniques for localization of sub-resolution fluorescent
      biomarkers.
AB  - In this article, we explore adaptive global and local segmentation techniques for
      a lab-on-chip nutrition monitoring system (NutriChip). The experimental setup
      consists of Caco-2 intestinal cells that can be artificially stimulated to
      trigger an immune response. The eventual response is optically monitored using
      immunofluoresence techniques targeting toll-like receptor 2 (TLR2). Two problems
      of interest need to be addressed by means of image processing. First, a new cell
      sample must be properly classified as stimulated or not. Second, the location of
      the stained TLR2 must be recovered in case the sample has been stimulated. The
      algorithmic approach to solving these problems is based on the ability of a
      segmentation technique to properly segment fluorescent spots. The sample
      classification is based on the amount and intensity of the segmented pixels,
      while the various segmenting blobs provide an approximate localization of TLR2. A
      novel local thresholding algorithm and three well-known spot segmentation
      techniques are compared in this study. Quantitative assessment of these
      techniques based on real and synthesized data demonstrates the improved
      segmentation capabilities of the proposed algorithm.

PMID- 24105984
TI  - The E693Delta (Osaka) mutation in amyloid precursor protein potentiates
      cholesterol-mediated intracellular amyloid beta toxicity via its impaired
      cholesterol efflux.
AB  - It has been shown that amyloid beta (Abeta) secretion regulates cholesterol
      efflux from cells and that the E693Delta (Osaka) mutation in amyloid precursor
      protein (APP) promotes intracellular accumulation of Abeta and thus reduces its
      secretion. These findings led us to speculate that APP with the Osaka mutation
      (APPOSK ) might have a defect in cholesterol efflux and thus cause cellular
      malfunction. We therefore examined the effects of this mutation on intracellular
      cholesterol transport and efflux in cultured cells. Upon cholesterol loading,
      APPOSK -expressing cells exhibited higher levels of cellular cholesterol than
      wild-type APP-expressing cells, suggesting impaired cholesterol efflux. It is
      known that, after its internalization, cholesterol is transported from the
      endosomes to the endoplasmic reticulum (ER) and Golgi apparatus and then to the
      plasma membrane. In APPOSK -expressing cells, cholesterol accumulated with Abeta
      in the ER and Golgi apparatus and alone in endosomes/lysosomes. These results
      imply that the mutation-induced disturbance of Abeta trafficking from the ER to
      the plasma membrane affects cholesterol transport to cause cholesterol
      accumulation in the ER and Golgi apparatus and, consequently, in endosomes.
      Furthermore, we detected an enhanced mitochondrial accumulation of Abeta and
      cholesterol in APPOSK -expressing cells, and this was accompanied by an increase
      in the generation of reactive oxygen species (ROS). The present findings suggest
      that Abeta trafficking is important for intracellular cholesterol transport and
      efflux and that the Osaka mutation potentiates cholesterol-dependent exacerbation
      of intracellular Abeta toxicity, i.e. Abeta-induced ROS generation, by disturbing
      Abeta-mediated cholesterol efflux from the cell.

PMID- 24105985
TI  - Preparation of biocompatible aggregation-induced emission homopolymeric
      nanoparticles for cell imaging.
AB  - A series of new homopolymers with various degrees of polymerization derived from
      vinyl tetraphenylethene, that is, poly[2-(4-vinylphenyl)ethene-1,1,2
      triyl)tribenzene] homopolymers, is synthesized by reversible addition
      fragmentation chain transfer (RAFT) polymerization. The homopolymers exhibit a
      significant aggregation-induced emission (AIE) effect and an ability to assemble
      themselves into AIE polymer nanoparticles (NPs) during precipitation in a
      water/tetrahydrofuran (THF) mixture. The NPs also exhibit good dispersibility,
      stability, and biocompatibility. The AIE polymer NPs are used in imaging studies
      of HeLa cells. 

PMID- 24105987
TI  - Does receiving an American Academy of Otolaryngology-Head and Neck Surgery
      Foundation Centralized Otolaryngology Research Efforts grant influence career
      path and scholarly impact among fellowship-trained rhinologists?
AB  - BACKGROUND: To determine whether American Academy of Otolaryngology-Head and Neck
      Surgery Foundation (AAO-HNSF) Centralized Otolaryngology Research Efforts (CORE)
      grants influence career paths and scholarly impact of fellowship-trained
      rhinologists, and whether funding from the National Institutes of Health (NIH)
      and CORE programs is associated with increased scholarly impact among
      rhinologists. Another aim was to explore whether obtaining CORE grant funding is
      associated with NIH award acquisition. METHODS: Practice setting, academic rank,
      and fellowship-training status were determined for individuals in the CORE grant
      database. The h-index and publication experience of practitioners was calculated
      using the Scopus database. Faculty listings were used to determine this data for
      a non-CORE-grants-funded "control" group of academic rhinologists. Active and
      past NIH funding was obtained using the NIH RePORTER database. RESULTS: Fifteen
      of 26 (57.7%) fellowship-trained rhinologists receiving CORE grants were funded
      for rhinologic projects. Five of 6 rhinologists receiving NIH funding had a CORE
      grants-funding history. Twenty-two of 26 (84.6%) rhinologists receiving CORE
      funding are currently in academic practice. Academic rhinologists receiving CORE
      or NIH funding had higher h-indices, a result reaching significance among
      promoted faculty and those with greater than 10 years of publication experience.
      CONCLUSION: Encouraging the pursuit of CORE grants among junior faculty as well
      as trainees interested in rhinology may be a strategy for developing highly
      effective research habits that pay dividends after the first few years of one's
      career. Fellowship-trained rhinologists with a CORE funding history predominantly
      pursue careers in academic medicine, although their CORE projects are not
      necessarily related to rhinologic topics.

PMID- 24105986
TI  - Differential sensitivity to JAK inhibitory drugs by isogenic human erythroblasts
      and hematopoietic progenitors generated from patient-specific induced pluripotent
      stem cells.
AB  - Disease-specific induced pluripotent stem cells (iPSCs) provide an unprecedented
      opportunity to establish novel disease models and accelerate drug development
      using distinct tissue target cells generated from isogenic iPSC lines with and
      without disease-causing mutations. To realize the potential of iPSCs in modeling
      acquired diseases which are usually heterogeneous, we have generated multiple
      iPSC lines including two lines that are JAK2-wild-type and four lines homozygous
      for JAK2-V617F somatic mutation from a single polycythemia vera (PV) patient
      blood. In vitro differentiation of the same patient-derived iPSC lines have
      demonstrated the differential contributions of their parental hematopoietic
      clones to the abnormal erythropoiesis including the formation of endogenous
      erythroid colonies. This iPSC approach thus may provide unique and valuable
      insights into the genetic events responsible for disease development. To examine
      the potential of iPSCs in drug testing, we generated isogenic hematopoietic
      progenitors and erythroblasts from the same iPSC lines derived from PV patients
      and normal donors. Their response to three clinical JAK inhibitors, INCB018424
      (Ruxolitinib), TG101348 (SAR302503), and the more recent CYT387 was evaluated.
      All three drugs similarly inhibited erythropoiesis from normal and PV iPSC lines
      containing the wild-type JAK2 genotype, as well as those containing a homozygous
      or heterozygous JAK2-V617F activating mutation that showed increased
      erythropoiesis without a JAK inhibitor. However, the JAK inhibitors had less
      inhibitory effect on the self-renewal of CD34+ hematopoietic progenitors. The
      iPSC-mediated disease modeling thus underlies the ineffectiveness of the current
      JAK inhibitors and provides a modeling system to develop better targeted
      therapies for the JAK2 mutated hematopoiesis.

PMID- 24105988
TI  - On two different objectives of the concepts of ionic radii.
AB  - Experimentally and theoretically derived interatomic distances (D) and ionic
      radii (R) of more than a hundred monomeric (AX), dimeric (A2X2, ABXY), and
      crystalline ([AX]) alkali halide species (A=Li, Na, K, Rb, Cs, Fr; X=H, F, Cl,
      Br, I, At) have been analyzed. Chemists use the word "atomic radius" for two
      antithetic concepts. Let D(CiEE'jj') be the "billion" of distances i between two
      adjacent atoms in the millions of known compounds C from a hundred different
      elements E in bonding states j. The common chemical aim is partitioning D
      approximately into increments R(Ej) +R(E'j'). This can be achieved with a few
      (say <thousand) predictive constants R(Ej). An antipodal aim is specifying in
      hindsight an electron density feature in the "billion" of different bonds i, by
      partitioning them into "two billions" of exact bonded radii R(E)(Ci) + R(E')(Ci).
      The constant incremental and the variable bonded radii concepts with the same
      generic name are useful in different fields of research. Different concepts
      should be well distinguished, since they have different meaning, different
      numerical values, and different purposes.

PMID- 24105989
TI  - Characterization of the attachment mechanisms of tissue-derived cell lines to
      blood-compatible polymers.
AB  - Recent advances in biomedical engineering require the development of new types of
      blood-compatible polymers that also allow non-blood cell attachment for the
      isolation of stem cells and circulating tumor cells (CTCs) from blood and for the
      development of artificial organs for use under blood-contact conditions. Poly(2
      methoxyethyl acrylate) (PMEA) and poly(tetrafurfuryl acrylate) (PTHFA) were
      previously identified as blood-compatible polymers. Here, it is demonstrated that
      cancer cells can attach to the PMEA and PTHFA substrates, and the differences in
      the attachment mechanisms to the PMEA and PTHFA substrates between cancer cells
      and platelets are investigated. It is also found that the adsorption-induced
      deformation of fibrinogen, which is required for the attachment and activation of
      platelets, does not occur on the PMEA and PTHFA substrates. In contrast,
      fibronectin is deformed on the PMEA and PTHFA substrates. Therefore, it is
      concluded that cancer cells and not platelets can attach to the PMEA and PTHFA
      substrates based on this protein-deformation difference between these substrates.
      Moreover, it is observed that cancer cells attach to the PMEA substrate via both
      integrin-dependent and -independent mechanisms and attach to the PTHFA substrate
      only through an integrin-dependent mechanism. It is expected that PMEA and PTHFA
      will prove useful for blood-contact biomedical applications.

PMID- 24105990
TI  - Equilibrium topology and partial inversion of Janus drops: a numerical analysis.
AB  - The equilibrium topology of an aqueous Janus emulsion of two oils, O1 and O2,
      with water, W, [(O1+O2)/W], is numerically evaluated with the following realistic
      interfacial tensions (gamma): gammaO2/W =5 mN m(-1) , gammaO1/O2 =1 mN m(-1) ,
      and gammaO1/W varies within the range 4-5 mN m(-1) , which is the limiting range
      for stable Janus drop topology. The relative significance of the two
      independently pivotal factors for the topology is evaluated, that is, the local
      equilibrium at the line of contact between the three liquids and the volume
      fraction of the two dispersed liquids within the drop. The results reveal a
      dominant effect of the local equilibrium on the fraction of the O2 drop surface
      that is covered by O1. In contrast, for a constant volume of O2, the impact of
      the interfacial tension balance on the limit of the coverage is modest for an
      infinite volume of O1. Interestingly, when the O1 volume exceeds this value, an
      emulsion inversion occurs, and the O1 portion of the (O1+O2)/W topology becomes a
      continuous phase, generating a (W+O2)/O1 Janus configuration. 

PMID- 24105991
TI  - Hepatocyte nuclear factor-1beta (HNF-1beta) promotes glucose uptake and
      glycolytic activity in ovarian clear cell carcinoma.
AB  - Ovarian clear cell carcinoma (OCCC) is a morphologically and biologically
      distinct subtype of ovarian carcinomas that often arises in ovarian
      endometriosis. We previously reported that a unique carcinogenic environment,
      especially iron-induced oxidative stress in endometriotic cysts may promote
      development of OCCC. We also identified a gene expression profile characteristic
      of OCCC (the "OCCC signature"). This 320-gene OCCC signature is enriched in genes
      associated with stress response and sugar metabolism. However, the biological
      implication of this profile is unclear. In this study, we have focused on the
      biological role of the HNF-1beta gene within the OCCC signature, which was
      previously shown to be overexpressed in OCCC. Suppression of HNF-1beta in the HNF
      1beta-overexpressing human ovarian cancer cell line RMG2 using short hairpin RNA
      resulted in a significant increase in proliferation. It also facilitated glucose
      uptake, glycolytic activity, and lactate secretion along with increased
      expression of the glucose transporter-1 (GLUT-1) gene and several key enzymes in
      the glycolytic process. Conversely, forced expression of HNF-1beta in the serous
      ovarian cancer cell line, Hey, resulted in slowed cellular growth and repressed
      glycolytic activity. These data suggest that HNF-1beta represses cell growth, and
      at the same time, it promotes aerobic glycolysis which is known as the "Warburg
      effect." As the Warburg effect is regarded as a characteristic metabolic process
      in cancer which may contribute to cell survival under hypoxic conditions or in a
      stressful environment, overexpression of HNF-1beta may play an inevitable role in
      the occurrence of OCCC in stressful environment.

PMID- 24105992
TI  - The labyrinth of interactions of Epstein-Barr virus-encoded small RNAs.
AB  - Epstein-Barr Virus (EBV) is an oncogenic herpesvirus implicated in the
      pathogenesis of a number of human malignancies. However, the mechanism by which
      EBV leads to malignant transformation is not clear. A number of viral latent gene
      products, including non-protein coding small RNAs, are believed to be involved.
      Epstein-Barr virus-encoded RNA 1 (EBER1) and EBER2 are two such RNA molecules
      that are abundantly expressed (up to 10(7) copies) in all EBV-infected cells, but
      their function remains poorly understood. These polymerase III transcripts have
      extensive secondary structure and exist as ribonucleoproteins. An accumulating
      body of evidence suggests that EBERs play an important role, directly or
      indirectly, in EBV-induced oncogenesis. Here, we summarize the current
      understanding of the complex interactions of EBERs with various cellular factors
      and the potential pathways by which these small RNAs are able to influence EBV
      infected cells to proliferate and to induce tumorigenesis. The exosome pathway is
      probably involved in the cellular excretion of EBERs and facilitating some of
      their biological effects.

PMID- 24105993
TI  - Arctic marine fishes and their fisheries in light of global change.
AB  - In light of ocean warming and loss of Arctic sea ice, harvested marine fishes of
      boreal origin (and their fisheries) move poleward into yet unexploited parts of
      the Arctic seas. Industrial fisheries, already in place on many Arctic shelves,
      will radically affect the local fish species as they turn up as unprecedented
      bycatch. Arctic marine fishes are indispensable to ecosystem structuring and
      functioning, but they are still beyond credible assessment due to lack of basic
      biological data. The time for conservation actions is now, and precautionary
      management practices by the Arctic coastal states are needed to mitigate the
      impact of industrial fisheries in Arctic waters. We outline four possible
      conservation actions: scientific credibility, 'green technology', legitimate
      management and overarching coordination. 

PMID- 24105994
TI  - Adsorption, activation, and dissociation of oxygen on doped oxides.
AB  - Charge transfer in the presence of dopants is relevant for the adorption and
      activation of small molecules, such as O2 . Scanning tunneling microscopy and DFT
      calculations provide evidence for the formation of strongly bound superoxo
      species on chemically inert, Mo-doped CaO films. This oxygen surface species
      shows a high propensity to dissociate. Dopants could also be important for the
      activation of hydrocarbons on inert oxides. 

PMID- 24105995
TI  - Palladium-catalyzed through-space C(sp(3))-H and C(sp(2))-H bond activation by
      1,4-palladium migration: efficient synthesis of [3,4]-fused oxindoles.
AB  - Palladium two step: Linear anilides were converted into the title compounds in
      good to excellent yields through a palladium-catalyzed domino
      carbopalladation/1,4-palladium shift sequence. The C(sp(3) )-H activation
      involves a seven-membered palladacycle, and is chemoselective in the presence of
      competitive C(sp(2) )?H bonds. DMA=N,N-dimethylacetamide, OPiv=pivalate. 

PMID- 24105996
TI  - Hollow AgI:Ag nanoframes as solar photocatalysts for hydrogen generation from
      water reduction.
AB  - A facile strategy based on the principle of the Kirkendall effect has been
      developed to synthesize hollow nanoframes and nanoshells of AgI:Ag composites
      through the controlled anion-exchange reaction between I(-) ions and solid
      AgBr:Ag (or AgCl:Ag) nanoparticles that serve as templates. Regardless of the
      morphologies of the template nanoparticles, they can be chemically transformed to
      hollow AgI:Ag structures with morphologies similar to those of the templates. The
      synthesized hollow AgI:Ag nanostructures can be used as efficient photocatalysts
      for H2 generation from water reduction and the decomposition of organic
      pollutants owing to the enhanced absorption of visible light by the Ag components
      in the hybrid nanostructures. The hollow nanostructures exhibit a higher
      photocatalytic performance than the corresponding solid nanoparticles possibly
      because of the large surface area and unique AgI/Ag interfaces associated with
      the hollow nanostructures. 

PMID- 24105997
TI  - Probiotics determine hypolipidemic and antioxidant effects in hyperlipidemic
      hamsters.
AB  - SCOPE: Hyperlipidemia, hyperglycemia, and the oxidative stress are among the
      known risk factors of atherosclerosis. Our aim was to assess the hypolipidemic
      and antioxidant effects of a probiotic mix (Lactobacillus acidophilus and
      Bifidobacterium animalis) in hyperlipidemic hamsters (HL). METHODS AND RESULTS:
      Male Golden Syrian hamsters developed hyperlipidemia after 21 weeks of fat diet.
      For the last 5 weeks of experiment, ten HL were treated with the probiotic mix
      (HLP), ten received water (HL). Ten animals received standard chow (N). Increase
      of plasma total cholesterol (TC), triglycerides (TG), phospholipids (PL),
      oxidized LDL, glucose, of 4-hydroxynonenal (4-HNE) in plasma, liver, and
      myocardium, and of intestinal Niemann Pick C1 like 1 (NPC1L1) and microsomal TG
      transfer protein (MTTP) expression was observed in HL versus N. The probiotic mix
      decreased plasma TC, TG, PL, oxidized LDL, 4-HNE, and glucose levels and
      increased paraoxonase-1 activity, decreased NPC1L1 and MTTP protein expression
      compared to HL. In HLP liver, a significant reduction of TC, TG, and fatty acids
      was observed. PL increased and 4-HNE levels decreased in the liver and myocardium
      of HLP versus HL. CONCLUSION: Our data support the administration of probiotics
      to humans because of their hypolipidemic (through decreasing intestinal NPC1L1
      and MTTP) and antioxidant effects (stimulating HDL-associated paraoxonase-1).

PMID- 24105998
TI  - Size matters: Filamentous bacteria drive interstitial vortex formation and colony
      expansion in Paenibacillus vortex.
AB  - The beautiful patterns formed by motile bacteria have always intrigued the
      curious (Ben-Jacob et al., Eur. Phys. J. B 2008;65:315-322). The mechanisms
      underlying their formation are believed to play a role in a range of natural
      phenomena, including embryogenesis, animal behavior, and economics. There has
      been significant effort to develop tools for characterizing the behavior of
      individual cells within large populations of migrating bacteria; a prerequisite
      for studying self-organization in this context (Garner, Mol. Micro. 2011;80:577
      579). Here, I apply powerful computer vision methods to study P. vortex
      interstitial colony expansion. Quantitative observations show how exceptionally
      long bacteria play a catalytic role-both in vortex formation, which had to date
      remained somewhat mysterious-and in facilitating colony expansion. This
      highlights the functional importance of bacterial morphology in bridging the
      microscopic and macroscopic scales, and it reshapes our understanding of vortex
      forming bacteria.

PMID- 24106000
TI  - Effect of TAT-obestatin on proliferation, differentiation, apoptosis and
      lipolysis in 3T3-L1 preadipocytes.
AB  - It has been reported that obestatin regulates adipocyte metabolism via receptors
      on the cell surface. We wondered whether obestatin can interact with
      intracellular components that activated signalling pathways in adipocytes.
      Because obestatin (human) only presents one lysine (at position 10), which cannot
      penetrate the cell membrane, therefore, we used a cell-permeable peptide TAT (49
      57) as a vector to carry obestatin across the cell membrane. The goal of this
      study was to further understand the function of obestatin after penetrating the
      cell membrane. Our results showed that TAT-obestatin could cross the 3T3-L1 cell
      membrane in the absence of cytotoxicity. TAT-obestatin showed no effect on the
      proliferation of 3T3-L1 preadipocytes. In contrast, obestatin significantly
      stimulated proliferation at a dose of 10(-11)  M and 10(-13)  M. In addition, TAT
      obestatin demonstrated a more potent inhibitory effect on cell apoptosis induced
      by serum starvation than that of obestatin. During the progress of adipocyte
      differentiation, TAT-obestatin and obestatin had no effect on adipogenesis. In
      the lipolysis assay, TAT-obestatin significantly increased glycerol and free
      fatty acid release from 3T3-L1 adipocytes after 3 h treatment but showed no
      significant effect on lipolysis after 24 h and 48 h of treatment. In contrast,
      obestatin (10(-7)  M) had no effect on glycerol release after 3, 24 and 48 h of
      treatment. The difference between the effect of TAT-obestatin and obestatin on
      adipocytes metabolism indicated that TAT-obestatin may trigger intracellular
      signalling as well as signalling at the cell membrane.

PMID- 24105999
TI  - Postsynaptic assembly: a role for Wnt signaling.
AB  - Synapse formation requires the coordinated formation of the presynaptic terminal,
      containing the machinery for neurotransmitter release, and the postsynaptic side
      that possesses the machinery for neurotransmitter reception. For coordinated pre-
      and postsynaptic assembly signals across the synapse are required. Wnt secreted
      proteins are well-known synaptogenic factors that promote the recruitment of
      presynaptic components in diverse organisms. However, recent studies demonstrate
      that Wnts act directly onto the postsynaptic side at both central and peripheral
      synapses to promote postsynaptic development and synaptic strength. This review
      focuses on the role of Wnts in postsynaptic development at central synapses and
      the neuromuscular junction.

PMID- 24106001
TI  - Block copolymer templated assembly of active Pd nanocube arrays.
AB  - Two-dimensional (2D) palladium nanocube array is achieved on plasma-etched block
      copolymer templates, while the well-aligned nanocubes remain active. Anisotropic
      nanocubes are site-selectively assembled on various nanopatterns by capillary
      force. The nanocube array is proved to be easily tunable, and the dimensional
      commensurability plays a key role in the configurations of the nanocube
      assemblies. Not only catalytic nanocube array under confinement but also template
      for the growth of nanoscale zinc oxide (ZnO) nanorods is exemplified as the
      potential application of the nanoarray. 

PMID- 24106002
TI  - Albumin-based nanocomposite spheres for advanced drug delivery systems.
AB  - A novel drug delivery system incorporating human serum albumin, poly(lactic-co
      glycolic acid, magnetite nanoparticles, and therapeutic agent(s) was developed
      for potential application in the treatment of diseases such as rheumatoid
      arthritis and skin cancer. An oil-in-oil emulsion/solvent evaporation (O/OSE)
      method was modified to produce a drug delivery system with a diameter of 0.5-2
      MUm. The diameter was mainly controlled by adjusting the viscosity of albumin in
      the discontinuous phase of the O/OSE method. The drug-release study showed that
      the release of drug and albumin was mostly dependent on the albumin content of
      the drug delivery system, which is very similar to the drug occlusion-mesopore
      model. Cytotoxicity tests indicated that increasing the albumin content in the
      drug delivery system increased cell viability, possibly due to the improved
      biocompatibility of the system. Overall, these studies show that the proposed
      system could be a viable option as a drug delivery system in the treatment of
      many illnesses, such as rheumatoid arthritis, and skin and breast cancers.

PMID- 24106003
TI  - Functionalization of polycarbonate surfaces by grafting PEG and zwitterionic
      polymers with a multicomb structure.
AB  - The hemocompatibility of polycarbonateurethane (PCU) surfaces is improved by
      decoration with poly(poly(ethylene glycol) methacrylate) (poly(PEGMA)) and
      zwitterionic poly(3-((2-(methacryloyloxy)ethyl)dimethylammonio)propane-1
      sulfonate) (poly(DMAPS)) blocks providing a novel multicomb structure obtained by
      application of surface-initiated atom transfer radical polymerization (s-ATRP)
      conditions. The PCU-poly(PEGMA-g-DMAPS) surface shows high hydrophilicity with a
      low contact angle of 20.6 +/- 1.8 degrees , while PCU-poly(PEGMA-b-DMAPS) surface
      exhibitsed a contact angle of 30.5 +/- 2.6 degrees . Furthermore, PCU-poly(PEGMA
      g-DMAPS) surface shows very low platelet adsorption indicating that multicomb
      structure modified PCUs are preferred candidate materials for blood-contacting
      materials.

PMID- 24106005
TI  - Composite polymer electrolytes for fuel cell applications: filler-induced effect
      on water sorption and transport properties.
AB  - Nafion- and sulfonated polysulfone (SPS)- based composite membranes were prepared
      by incorporation of SnO2 nanoparticles in a wide range of loading (0${ ?div }$35
      wt. %). The composites were investigated by differential scanning calorimetry,
      dynamic vapor sorption and electrochemical impedance spectroscopy to study the
      filler effect on water sorption, water mobility, and proton conductivity. A
      detrimental effect of the filler was observed on water mobility and proton
      conductivity of Nafion-based membranes. An increase in water mobility and proton
      conductivity was instead observed in SPS-based samples, particularly at low
      hydration degree. Analysis of the water sorption isotherms and states of water
      revealed that the presence of SnO2 in SPS enhances interconnectivity of
      hydrophilic domains, while not affecting the Nafion microstructure. These results
      enable the design of suitable electrolyte materials that operate in proton
      exchange membrane fuel cell conditions. 

PMID- 24106004
TI  - Effects of breathing frequency and flow rate on the total inward leakage of an
      elastomeric half-mask donned on an advanced manikin headform.
AB  - OBJECTIVES: The objective of this study was to investigate the effects of
      breathing frequency and flow rate on the total inward leakage (TIL) of an
      elastomeric half-mask donned on an advanced manikin headform and challenged with
      combustion aerosols. METHODS: An elastomeric half-mask respirator equipped with
      P100 filters was donned on an advanced manikin headform covered with life-like
      soft skin and challenged with aerosols originated by burning three materials:
      wood, paper, and plastic (polyethylene). TIL was determined as the ratio of
      aerosol concentrations inside (C in) and outside (C out) of the respirator (C
      in/C out) measured with a nanoparticle spectrometer operating in the particle
      size range of 20-200nm. The testing was performed under three cyclic breathing
      flows [mean inspiratory flow (MIF) of 30, 55, and 85 l/min] and five breathing
      frequencies (10, 15, 20, 25, and 30 breaths/min). A completely randomized
      factorial study design was chosen with four replicates for each combination of
      breathing flow rate and frequency. RESULTS: Particle size, MIF, and combustion
      material had significant (P < 0.001) effects on TIL regardless of breathing
      frequency. Increasing breathing flow decreased TIL. Testing with plastic aerosol
      produced higher mean TIL values than wood and paper aerosols. The effect of the
      breathing frequency was complex. When analyzed using all combustion aerosols and
      MIFs (pooled data), breathing frequency did not significantly (P = 0.08) affect
      TIL. However, once the data were stratified according to combustion aerosol and
      MIF, the effect of breathing frequency became significant (P < 0.05) for all MIFs
      challenged with wood and paper combustion aerosols, and for MIF = 30 l/min only
      when challenged with plastic combustion aerosol. CONCLUSIONS: The effect of
      breathing frequency on TIL is less significant than the effects of combustion
      aerosol and breathing flow rate for the tested elastomeric half-mask respirator.
      The greatest TIL occurred when challenged with plastic aerosol at 30 l/min and at
      a breathing frequency of 30 breaths/min.

PMID- 24106006
TI  - Interferon gamma causes olfactory dysfunction without concomitant neuroepithelial
      damage.
AB  - BACKGROUND: Olfactory loss is a debilitating symptom of chronic rhinosinusitis
      (CRS). The pathophysiology of inflammatory olfactory dysfunction likely involves
      both conductive and sensorineural components. To study the interaction of CRS
      associated inflammatory cytokines with the olfactory epithelium (OE), a
      transgenic mouse model was developed that allows temporally-controlled local gene
      expression. Interferon-gamma (IFN-gamma) is a prototypical T helper 1 (Th1)
      cytokine linked to nonpolypoid CRS (CRSsNP), as well as sinonasal viral and
      bacterial infections. In this study, the effects of chronic IFN-gamma expression
      on olfactory histology and function were investigated. METHODS: IFN-gamma
      secretion by olfactory sustentacular cells was induced in the transgenic mouse.
      Viability and gross behavior were unaffected. Mice were euthanized after 6 weeks
      of IFN-gamma expression, and olfactory tissue was studied by histology,
      immunohistochemistry, and electro-olfactography (EOG). Findings were compared
      with uninduced littermates. RESULTS: IFN-gamma expression did not result in
      alteration of the normal histologic architecture of the neuroepithelium or lamina
      propria. However, EOG recordings demonstrated a significant decrease in odorant
      responses after IFN-gamma expression. In addition, a marked increase in
      submucosal CD45-positive cells was observed, the majority of which were CD3
      positive and CD4-positive lymphocytes. CONCLUSION: Chronic IFN-gamma expression
      in the mouse OE results in diminished odorant responsiveness, despite the absence
      of inflammatory tissue damage. This suggests a direct effect of IFN-gamma on
      olfactory neuron function that may underlie olfactory loss in CRSsNP or viral
      infections. The infiltration of submucosal lymphocytes raises the possibility
      that other downstream cytokines also contribute to olfactory dysfunction.

PMID- 24106007
TI  - Can selenium be a modifier of cancer risk in CHEK2 mutation carriers?
AB  - Selenium is an essential trace element for humans, playing an important role in
      various major metabolic pathways. Selenium helps to protect the body from the
      poisonous effects of heavy metals and other harmful substances. Medical studies
      have provided evidence of selenium supplementation in preventing certain cancers.
      Low and too high selenium (Se) status correlates with increased risk of e.g.
      lung, larynx, colorectal and prostate cancers. A higher level of selenium and
      supplementation with selenium has been shown to be associated with substantially
      reduced cancer mortality. Selenium exerts its biological roles through
      selenoproteins, which are involved in oxidoreductions, redox signalling,
      antioxidant defence, thyroid hormone metabolism and immune responses. Checkpoint
      kinase 2 (CHEK2) is an important signal transducer of cellular responses to DNA
      damage and acts as a tumour suppressor gene. Mutations in the CHEK2 gene have
      been shown to be associated with increased risks of several cancers. Four common
      mutations in CHEK2 gene (1100delC, IVS2+1G>A, del5395 and I157T) have been
      identified in the Polish population. Studies have provided evidence that CHEK2
      truncating and/or missense mutations are associated with increased risk of
      breast, prostate, thyroid, colon and kidney cancers. The variability in
      penetrance and cancer expression in CHEK2 mutation carriers can probably be
      explained by the influence of other genetic or environmental factors. One of the
      possible candidates is Se, which together with genetic variations in
      selenoprotein genes may influence susceptibility to cancer risk. 

PMID- 24106008
TI  - Conducting polymer electrodes for electroencephalography.
AB  - Conducting polymer electrodes are developed on a flexible substrate for
      electroencephalography applications. These electrodes yield higher quality
      recordings than dry electrodes made from metal. Their performance is equivalent
      to commercial gel-assisted electrodes, paving the way for non-invasive, long-term
      monitoring of the human brain. 

PMID- 24106009
TI  - Targeted synthesis of porous aromatic frameworks and their composites for
      versatile, facile, efficacious, and durable antibacterial polymer coatings.
AB  - Novel quaternary pyridinium-type porous aromatic frameworks, PAF-50, and their
      composites, AgCl-PAF-50, have been synthesized to effectively and efficiently
      inhibit the growth of bacteria. Most importantly, both PAF-50 and AgCl-PAF-50
      have excellent compatibility with conventional polymers, which lead to great
      operation flexibility and versatility for antibactrial coatings on various
      medical devices simply via solution or spray coating. 

PMID- 24106010
TI  - RRBS-analyser: a comprehensive web server for reduced representation bisulfite
      sequencing data analysis.
AB  - In reduced representation bisulfite sequencing (RRBS), genomic DNA is digested
      with the restriction enzyme and then subjected to next-generation sequencing,
      which enables detection and quantification of DNA methylation at whole-genome
      scale with low cost. However, the data processing, interpretation, and analysis
      of the huge amounts of data generated pose a bioinformatics challenge. We
      developed RRBS-Analyser, a comprehensive genome-scale DNA methylation analysis
      server based on RRBS data. RRBS-Analyser can assess sequencing quality, generate
      detailed statistical information, align the bisulfite-treated short reads to
      reference genome, identify and annotate the methylcytosines (5mCs) and associate
      them with different genomic features in CG, CHG, and CHH content. RRBS-Analyser
      supports detection, annotation, and visualization of differentially methylated
      regions (DMRs) for multiple samples from nine reference organisms. Moreover, RRBS
      Analyser provides researchers with detailed annotation of DMR-containing genes,
      which will greatly aid subsequent studies. The input of RRBS-Analyser can be raw
      FASTQ reads, generic SAM format, or self-defined format containing individual 5mC
      sites. RRBS-Analyser can be widely used by researchers wanting to unravel the
      complexities of DNA methylome in the epigenetic community. RRBS-Analyser is
      freely available at http://122.228.158.106/RRBSAnalyser/. 

PMID- 24106011
TI  - Methane coupling over magnesium oxide: how doping can work.
AB  - Electronic doping of magnesium oxide catalysts has an effect on the oxidative
      coupling of methane. Highly active sites can be created by co-modification of MgO
      with iron and gold in ppm quantities. 

PMID- 24106012
TI  - Structure and function of an RNA-reading thermostable DNA polymerase.

PMID- 24106013
TI  - Age-related changes of healthy bone marrow cell signaling in response to growth
      factors provide insight into low risk MDS.
AB  - BACKGROUND: Single Cell Network Profiling (SCNP) is a multiparametric flow
      cytometry-based assay that quantifiably and simultaneously measures changes in
      intracellular signaling proteins in response to in vitro extracellular modulators
      at the single cell level. Myelodysplastic syndrome (MDS) is a heterogeneous
      clonal disorder of hematopoietic stem cells that occurs in elderly subjects and
      is characterized by dysplasia and ineffective hematopoiesis. The functional
      responsiveness of MDS bone marrow (BM) hematopoietic cells, including
      functionally distinct myeloid and erythroid precursor subsets, to hematopoietic
      growth factors (HGF) and the relationship of modulated signaling to disease
      characteristics is poorly understood. METHODS: SCNP was used first to examine the
      effects of age on erythropoietin (EPO) and granulocyte colony stimulating factor
      (GCSF)-induced signaling in myeloid, nucleated red blood cells (nRBC), and CD34
      expressing cell subsets in healthy BM (n = 15). SCNP was then used to map
      functional signaling profiles in low risk (LR) MDS (n = 7) for comparison to
      signaling in samples from healthy donors and to probe signaling associations
      within clinically defined subgroups. RESULTS: In healthy BM samples, signaling
      responses to HGF were quite homogeneous (i.e., tightly regulated) with age
      dependent effects observed in response to EPO but not to GCSF. Despite the
      relatively small number of samples assayed in the study, LR MDS could be
      classified into distinct subgroups based on both cell subset frequency and
      signaling profiles. CONCLUSIONS: As a correlate of underlying genetic
      abnormalities, signal transduction analyses may provide a functional and
      potentially clinically relevant classification of MDS. Further evaluation in a
      larger cohort is warranted.

PMID- 24106014
TI  - Preparation of 17beta-estradiol surface molecularly imprinted polymers and their
      application to the analysis of biological samples.
AB  - 17beta-Estradiol (E2) surface molecularly imprinted polymers have been prepared
      using functionalized monodispersed poly(glycidyl methacrylate-co-ethylene
      dimethacrylate) beads as a support. The resulting polymers were found to be
      uniform in size (5 MUm), and the surfaces of the microspheres possessed large
      pore-like structures. A chromatographic experiment demonstrated that the
      resulting microspheres exhibited high levels of recognition and selectivity
      toward the target molecule. The particles were employed as a novel sorbent in a
      molecularly imprinted SPE protocol. A method was then developed involving the
      combination of the pretreatment with HPLC to determine the levels of estrogen
      secreted from Michigan Cancer Foundation-7 cells. The obtained results revealed
      that the extraction recoveries of E2 from real samples were in the range of 73.0
      97.5% with RSDs of < 7.5% (n = 3). Calibration curves were established with R
      values > 0.9996 for concentrations in the range of 0.50-100.00 ng/mL. The LOD of
      this new method was 0.14 ng/mL. Compared with traditional C18 SPE agents, the
      particles showed high selectivity and extraction efficiency for E2 in the
      pretreatment process. The particles could therefore be used to determine trace
      estrogen in biological samples with a UV detector only. 

PMID- 24106016
TI  - Soil warming alters microbial substrate use in alpine soils.
AB  - Will warming lead to an increased use of older soil organic carbon (SOC) by
      microbial communities, thereby inducing C losses from C-rich alpine soils? We
      studied soil microbial community composition, activity, and substrate use after 3
      and 4 years of soil warming (+4  degrees C, 2007-2010) at the alpine treeline in
      Switzerland. The warming experiment was nested in a free air CO2 enrichment
      experiment using depleted (13)CO2 (delta(13)C = -300/00, 2001-2009). We traced
      this depleted (13)C label in phospholipid fatty acids (PLFA) of the organic layer
      (0-5 cm soil depth) and in C mineralized from root-free soils to distinguish
      substrate ages used by soil microorganisms: fixed before 2001 ('old'), from 2001
      to 2009 ('new') or in 2010 ('recent'). Warming induced a sustained stimulation of
      soil respiration (+38%) without decline in mineralizable SOC. PLFA concentrations
      did not reveal changes in microbial community composition due to soil warming,
      but soil microbial metabolic activity was stimulated (+66%). Warming decreased
      the amount of new and recent C in the fungal biomarker 18:2omega6,9 and the
      amount of new C mineralized from root-free soils, implying a shift in microbial
      substrate use toward a greater use of old SOC. This shift in substrate use could
      indicate an imbalance between C inputs and outputs, which could eventually
      decrease SOC storage in this alpine ecosystem.

PMID- 24106017
TI  - Controlled synthesis of nanosized palladium icosahedra and their catalytic
      activity towards formic-acid oxidation.
AB  - Pd icosahedra with sizes controlled in the range of 5-35 nm were synthesized in
      high purity through a combination of polyol reduction and seed-mediated growth.
      The Pd icosahedra were obtained with purity >94 % and uniform sizes controlled in
      the range of 5-17 nm by using ethylene glycol as both the reductant and solvent.
      The studies indicate that the formation of Pd nanocrystals with an icosahedral
      shape was very sensitive to the reaction kinetics. The success of this synthesis
      relies on the use of HCl to manipulate the reaction kinetics and thus control the
      twin structure and shape of the resultant nanocrystals. The size of the Pd
      icosahedra could be further increased up to 35 nm by seed-mediated growth, with
      17 nm Pd icosahedra serving as seeds. The multiply twinned Pd icosahedra could
      grow into larger sizes, and their shape and multiply twinned structure were
      preserved. Thanks to the presence of twin defects, the Pd icosahedra showed a
      catalytic current density towards formic-acid oxidation that was 1.9 and 11.6
      times higher than that of single-crystal Pd octahedra, which were also fully
      covered by {111} facets, and commercial Pd/C, respectively.

PMID- 24106018
TI  - Of elves and ethics: first, do no harm.

PMID- 24106015
TI  - Synthesis and biomedical applications of copper sulfide nanoparticles: from
      sensors to theranostics.
AB  - Copper sulfide (CuS) nanoparticles have attracted increasing attention from
      biomedical researchers across the globe, because of their intriguing properties
      which have been mainly explored for energy- and catalysis-related applications to
      date. This focused review article aims to summarize the recent progress made in
      the synthesis and biomedical applications of various CuS nanoparticles. After a
      brief introduction to CuS nanoparticles in the first section, we will provide a
      concise outline of the various synthetic routes to obtain different morphologies
      of CuS nanoparticles, which can influence their properties and potential
      applications. CuS nanoparticles have found broad applications in vitro,
      especially in the detection of biomolecules, chemicals, and pathogens which will
      be illustrated in detail. The in vivo uses of CuS nanoparticles have also been
      investigated in preclinical studies, including molecular imaging with various
      techniques, cancer therapy based on the photothermal properties of CuS, as well
      as drug delivery and theranostic applications. Research on CuS nanoparticles will
      continue to thrive over the next decade, and tremendous opportunities lie ahead
      for potential biomedical/clinical applications of CuS nanoparticles. 

PMID- 24106019
TI  - Does breastfeeding result in smarter children? A closer look.

PMID- 24106020
TI  - Skin to skin after cesarean birth.

PMID- 24106021
TI  - Who pays for the health benefits of exclusive breastfeeding? An analysis of
      maternal time costs.
AB  - BACKGROUND: The benefits of exclusive breastfeeding, including public health cost
      savings, are widely recognized, but breastfeeding requires maternal time
      investments. OBJECTIVE: This study investigates the time taken to exclusively
      breastfeed at 6 months compared with not exclusively breastfeeding. METHODS: Time
      use data were examined from an Australian survey of new mothers conducted during
      2005-2006. Data from 139 mothers with infants age 6 months were analyzed using
      chi-square tests of independence to examine socioeconomic and demographic
      characteristics and 2-sided t tests to compare average weekly hours spent on milk
      feeding, feeding solids, preparing feeds, and the total of these. The comparison
      was of exclusively breastfeeding mothers with other mothers. We also compared
      exclusively breastfeeding with partially breastfeeding and formula feeding
      mothers using a 1-way between-groups analysis of variance (ANOVA). RESULTS: The
      exclusively breastfeeding (vs other) mothers spent 7 hours extra weekly on milk
      feeding their infants but 2 hours less feeding solids. These differences were
      statistically significant. ANOVA revealed significant differences between
      exclusively breastfeeding mothers, breastfeeding mothers who had introduced
      solids, and mothers who fed any formula, in time spent feeding milk, and solids,
      and preparing feeds. CONCLUSION: Exclusive breastfeeding is time intensive, which
      is economically costly to women. This may contribute to premature weaning for
      women who are time-stressed, lack household help from family, or cannot afford
      paid help. Gaining public health benefits of exclusive breastfeeding requires
      strategies to share maternal lactation costs more widely, such as additional help
      with housework or caring for children, enhanced leave, and workplace lactation
      breaks and suitable child care.

PMID- 24106022
TI  - Response: should the World Health Organization's definition of predominant
      breastfeeding include fruit juice?

PMID- 24106023
TI  - Yes, the World Health Organization's definition of predominant breastfeeding
      should include fruit juice.

PMID- 24106028
TI  - Molecular analysis of the UV-inducible pili operon from Sulfolobus
      acidocaldarius.
AB  - Upon ultraviolet (UV) stress, hyperthermophilic Sulfolobus species show a highly
      induced transcription of a gene cluster responsible for pili biogenesis: the UV
      inducible pili operon (ups operon). This operon is involved in UV-induced pili
      assembly, cellular aggregation, and subsequent DNA exchange between cells. As the
      system increases the fitness of Sulfolobus cells after UV light exposure, we
      assume that transfer of DNA takes place in order to repair UV-induced DNA damages
      via homologous recombination. Here, we studied all genes present in the ups
      cluster via gene deletion analysis with a focus on UpsX, a protein that shows no
      identifiable functional domains. UspX does not seem to be structurally essential
      for UV-induced pili formation and cellular aggregation, but appears to be
      important for efficient DNA transfer. In addition, we could show that pilin
      subunits UpsA and UpsB probably both function as major pilin subunits in the ups
      pili. 

PMID- 24106029
TI  - A re-examination and re-evaluation of salamander orbital glands.
AB  - The amphibian integument contains numerous multicellular glands. Although two of
      these, the nasolabial and orbital glands and the associated nasolacrimal duct
      (NLD), have historically received considerable attention, interpretation of the
      original observations can be problematic in the context of current literature.
      Salamanders, in particular, are frequently regarded as at least indicative of
      aspects of the morphology of the common ancestor to all extant tetrapods; hence,
      an understanding of these glands in salamanders might prove to be informative
      about their evolution. For this study, the orbitonasal region of salamanders from
      three families was histologically examined. Three themes emerged: (1) examination
      of the effect of phylogeny on the nasolabial gland and NLD revealed a combination
      of features that may be unique to plethodontid salamanders, and may be correlated
      to their nose-tapping behavior by which substances are moved into the vomeronasal
      organ; (2) ecology appears to impact the relative development of the orbital
      glands, but not necessarily the nasolabial gland, with smaller glands being
      present in the aquatic species; (3) the nomenclature of the salamander orbital
      gland remains problematic, especially in light of comparative studies, as several
      alternate possibilities are viable. From this nomenclatural conundrum, however,
      it could be concluded that there may be a global pattern in the location of
      tetrapod orbital gland development. Molecular questions in terms of ontogeny and
      genetic homology affect the nature of the debate on orbital gland nomenclature.
      These observations suggest that rather than reflecting an ancestral condition,
      salamanders may instead represent a case of specialized, convergent evolution.

PMID- 24106030
TI  - How do pseudoenantiomers structurally differ in the gas phase? An IR/UV
      spectroscopy study of jet-cooled hydroquinine and hydroquinidine.
AB  - The gas-phase structures of the cinchona alkaloids, hydroquinine and its
      pseudoenantiomer hydroquinidine, are studied in a supersonic expansion by means
      of laser-induced fluorescence and IR/UV double-resonance spectroscopy.
      Vibrational spectroscopy combined with density functional calculations show that
      the conformational properties of the two pseudoenantiomers are identical. In both
      cases, they exist in two isoenergetic forms, with similar IR spectra. Both
      conformers are similar to the most stable cis-gamma-open form of quinine; they
      differ from each other by the position of the ethyl substituent attached to the
      quinuclidine ring. Further differences between the two conformers are observed in
      the laser-induced fluorescence spectrum. The first electronic transition is
      characterized by time-dependent density functional theory and RI-cc2
      calculations, and is of pipi* nature. The results described here emphasize the
      role of the ethyl substituent in the structural differences between
      pseudoenantiomers of cinchona alkaloids. 

PMID- 24106031
TI  - Time-resolved microfluorimetry: an alternative method for free radical and
      metabolic rate detection in microalgae.
AB  - Oxidative stress leads to an increase in the production of reactive oxygen
      species in cells and can be induced by environmental factors. To study free
      radical production in living microalgae, we use time-resolved microfluorimetry, a
      technology adopted from research on mammalian cells. In contrast to fluorescent
      probe-based measurements that rely on intensity changes, our sensor detects the
      presence of free radicals through collisional quenching, and is insensitive to
      most artifacts commonly observed with intensity-based methods. A new probe, 1
      pyrenebutanol allows estimation of free radicals production in the green
      microalga Tetraselmis ssp., for the first time. In addition, our method monitors
      simultaneously metabolic rate (through bound-free NAD(P)H ratio). Our results
      show that free radical production in algal cells is correlated to algal aging,
      and that during cell growth phases both intracellular free radicals and metabolic
      activity increase. Concerning thermal stress, we observe that rapid and low
      temperature changes (<10 degrees C) induce instantaneously an increase in ROS
      production. Our findings provide new insights into the production of free
      radicals in response to environmental stresses in unicellular green algae. 

PMID- 24106032
TI  - Composites for delivery of therapeutics: combining melt electrospun scaffolds
      with loaded electrosprayed microparticles.
AB  - A novel strategy is reported to produce biodegradable microfiber-scaffolds
      layered with high densities of microparticles encapsulating a model protein.
      Direct electrospraying on highly porous melt electrospun scaffolds provides a
      reproducible scaffold coating throughout the entire architecture. The burst
      release of protein is significantly reduced due to the immobilization of
      microparticles on the surface of the scaffold and release mechanisms are
      dependent on protein-polymer interactions. The composite scaffolds have a
      positive biological effect in contact with precursor osteoblast cells up to 18
      days in culture. The scaffold design achieved with the techniques presented here
      endorses these new composite scaffolds as promising templates for growth factor
      delivery. 

PMID- 24106033
TI  - [5,6]-Open methanofullerene derivatives of I(h)-C80.

PMID- 24106034
TI  - Distribution and size of mucous glands in the ferret tracheobronchial tree.
AB  - A transgenic ferret model of cystic fibrosis has recently been generated. It is
      probable that malfunction of airway mucous glands contributes significantly to
      the airway pathology of this disease. The usefulness of the ferret model may
      therefore depend in part on how closely the airway glands of ferrets resemble
      those of humans. Here, we show that in the ferret trachea glands are commonest in
      its most ventral aspect and disappear about half way up the lateral walls; they
      are virtually absent from the dorsal membranous portion. Further, the aggregate
      volume of glands per unit mucosal surface declines progressively by about 60%
      between the larynx and the carina. The average frequency of glands openings for
      the ferret trachea as a whole is only about one-fifth that in humans (where gland
      openings are found at approximately the same frequency throughout the trachea).
      Glands in the ferret trachea are on average about one-third the size of those in
      the human. Therefore, the aggregate volume of tracheal glands (per unit mucosal
      surface area) in the ferret is only about 6% that in humans. As in other
      mammalian species, airway glands in the ferret disappear at an airway internal
      diameter of ~1 mm, corresponding approximately in this species to airway
      generation 6.

PMID- 24106035
TI  - Determination of lignans in Wuweizi by using magnetic bar microextraction and
      HPLC.
AB  - In this paper, a magnetic bar microextraction was developed to extract
      schisandrin A, schisantherin A, and deoxyschizandrin from Wuweizi. The analytes
      were determined by HPLC. A stainless-steel wire was inserted into the hollow of
      the hollow fiber to make the magnetic bar. The bar can be used to stir the
      extraction system and extract the analytes, and was isolated from the extract
      system by magnetic force. Several experimental parameters, including type and
      volume of extraction solvent, the number of magnetic bars, extraction temperature
      and time, stirring speed and NaCl concentration were investigated and optimized.
      The LODs for schisandrin A, schisantherin A, and deoxyschizandrin were 0.14,
      0.06, and 0.10 g/mL, respectively. The recoveries were in the range of 70.90
      106.67% and the RSDs were < 8.84%. Compared with ultrasound-assisted and Soxhlet
      extraction, when the present method was applied, the extraction time was shorter,
      the sample amount was smaller, and the consumption of organic solvent was lower.

PMID- 24106036
TI  - Fluorescent silver nanoclusters in condensed DNA.
AB  - We study the formation and fluorescent properties of silver nanoclusters
      encapsulated in condensed DNA nanoparticles. Fluorescent globular DNA
      nanoparticles are formed using a dsDNA-cluster complex and polyallylamine as
      condensing agents. The fluorescence emission spectrum of single DNA nanoparticles
      is obtained using tip-enhanced fluorescence microscopy. Fluorescent clusters in
      condensed DNA nanoparticles appear to be more protected against destructive
      damage in solution compared to clusters synthesized on a linear polymer chain.
      The fluorescent clusters on both dsDNA and ssDNA exhibit the same emission bands
      (at 590 and 680 nm) and the same formation efficiency, which suggests the same
      binding sites. By using density functional theory, we show that the clusters may
      bind to the Watson-Crick guanine-cytosine base pairs and to single DNA bases with
      about the same affinity. 

PMID- 24106037
TI  - Incidence and long-term risk of de novo malignancies after liver transplantation
      with implications for prevention and detection.
AB  - The goal of this study was the characterization of long-term cancer risks after
      liver transplantation (LT) with implications for prevention and detection. Site
      specific cancer incidence rates and characteristics were compared retrospectively
      for 2000 LT patients from a single institution (January 1, 1983 to December 31,
      2010) and the general German population with standardized incidence ratios
      (SIRs); the total follow-up at December 31, 2011 was 14,490 person-years. The
      cancer incidence rates for the LT recipients were almost twice as high as those
      for the age- and sex-matched general population (SIR = 1.94, 95% CI = 1.63-2.31).
      Significantly increased SIRs were observed for vulvar carcinoma (SIR = 23.80),
      posttransplant lymphoproliferative disorder/non-Hodgkin lymphoma (SIR = 10.95),
      renal cell carcinoma (SIR = 2.65), lung cancer (SIR = 1.85), and colorectal
      cancer (SIR = 1.41). The mean time between transplantation and diagnosis was 6.8
      years. The mean age at the time of diagnosis was significantly lower for the
      cohort versus the general population with similar malignancies [50 years (both
      sexes) versus 69 and 68 years (males and females), P <= 0.006]. Tumors were
      diagnosed at more advanced stages, and there was a trend of higher grading, which
      suggested more aggressive tumor growth. Tumor treatment was performed according
      to accepted guidelines. Surprisingly, 5-year survival was slightly better in the
      study cohort versus the general population for renal cell carcinoma, lung cancer,
      colorectal cancer, and thyroid cancer. Long-term immunosuppression with different
      protocols did not lead to significantly different SIRs, although patients treated
      with mycophenolate mofetil had the lowest SIR for de novo cancers (1.65, 95% CI =
      1.2-2.4). Alcoholic liver disease (SIR = 2.30) and primary sclerosing cholangitis
      (SIR = 3.40) as indications for LT were associated with an increased risk of de
      novo malignancies. In conclusion, risk-adapted cancer surveillance is proposed.
      Tumor treatment performed according to accepted guidelines appears adequate.
      Mycophenolate may lead to lower long-term risks for de novo cancers.

PMID- 24106038
TI  - Changes to cytopathology training program requirements.

PMID- 24106040
TI  - Efficient room-temperature near-infrared detection with solution-processed
      networked single wall carbon nanotube field effect transistors.
AB  - Efficient room temperature NIR detection with sufficient current gain is made
      with a solution-processed networked SWNT FET. The high performance NIR-FET with
      significantly enhanced photocurrent by more than two orders of magnitude compared
      to dark current in the depleted state is attributed to multiple Schottky barriers
      in the network, each of which absorb NIR and effectively separate photocarriers
      to corresponding electrodes. 

PMID- 24106039
TI  - Engineering stress tolerance of Escherichia coli by stress-induced mutagenesis
      (SIM)-based adaptive evolution.
AB  - Microbial tolerance to toxic products and biomass hydrolysates is a challenge for
      the production of fuels and chemicals from renewable resources. To improve
      cellular tolerance to these environmental stresses, a novel adaptive evolutionary
      strategy based on stress-induced mutagenesis (SIM) was developed using non
      dividing cells. The concept of this method was proved using Escherichia coli FC40
      as a model strain, which was used to quantitatively evaluate the rate of SIM. By
      deleting either the mutL or mutS gene to disturb the mismatch repair activity of
      the host cells, the SIM rate under stressful conditions increased by 92- and 57
      fold, respectively. A periodic SIMbased adaptive evolution procedure, which
      synchronized the mutagenesis and the selection process in a single plate
      incubation step, was then developed using the mutL-deleted mutant. E. coli
      mutants tolerant to high concentrations of butanol (13 g/L), NaCl (95 g/L), and
      high temperature (50 degrees C) were obtained. These results indicate that stress
      induced adaptive evolution in non-dividing cells is an effective approach that
      can improve microbial tolerance against various stresses and generate robust
      microbial strains suitable for production of fuels and chemicals.

PMID- 24106041
TI  - Low-temperature degradation of a Y-TZP ceramic after surface treatments.
AB  - The purpose of this study was to evaluate the influence of zirconia surface
      treatments on low-temperature degradation (LTD). Disc-shaped specimens were
      subjected to one of four surface treatments, denoted as C (control-no surface
      treatment), Si (air abrasion with 30 um silica-modified alumina particles), Al
      (air abrasion with 30 um alumina particles), and Gr (grinding with 120 grit
      diamond discs). Half of the samples were submitted to autoclave treatment for 12
      h (127 degrees C, 1.5 bar). Samples were characterized by x-ray diffraction and
      profilometer analysis and were subjected to biaxial flexural strength test. All
      of the groups exhibited an increase in the amount of monoclinic phase (m-phase)
      after LTD. The t->m transformation was remarkable for the specimens from the C
      group, which also exhibited a significant increase in strength. The Gr group also
      exhibited an increase in strength but lower initial roughness, which probably
      suppressed LTD on the zirconia surface. The specimens subjected to air abrasion
      exhibited higher initial amounts of m-phase and a small increase in m-phase after
      LTD; the strength was not affected in these groups. The effects of LTD were
      different with each surface treatment applied. Apparently, LTD may be suppressed
      by smoother surfaces or the presence of an initial amount of m-phase on zirconia
      surface.

PMID- 24106042
TI  - Forecasting the viability of sea turtle eggs in a warming world.
AB  - Animals living in tropical regions may be at increased risk from climate change
      because current temperatures at these locations already approach critical
      physiological thresholds. Relatively small temperature increases could cause
      animals to exceed these thresholds more often, resulting in substantial fitness
      costs or even death. Oviparous species could be especially vulnerable because the
      maximum thermal tolerances of incubating embryos is often lower than adult
      counterparts, and in many species mothers abandon the eggs after oviposition,
      rendering them immobile and thus unable to avoid extreme temperatures. As a
      consequence, the effects of climate change might become evident earlier and be
      more devastating for hatchling production in the tropics. Loggerhead sea turtles
      (Caretta caretta) have the widest nesting range of any living reptile, spanning
      temperate to tropical latitudes in both hemispheres. Currently, loggerhead sea
      turtle populations in the tropics produce nearly 30% fewer hatchlings per nest
      than temperate populations. Strong correlations between empirical hatching
      success and habitat quality allowed global predictions of the spatiotemporal
      impacts of climate change on this fitness trait. Under climate change, many sea
      turtle populations nesting in tropical environments are predicted to experience
      severe reductions in hatchling production, whereas hatching success in many
      temperate populations could remain unchanged or even increase with rising
      temperatures. Some populations could show very complex responses to climate
      change, with higher relative hatchling production as temperatures begin to
      increase, followed by declines as critical physiological thresholds are exceeded
      more frequently. Predicting when, where, and how climate change could impact the
      reproductive output of local populations is crucial for anticipating how a
      warming world will influence population size, growth, and stability.

PMID- 24106043
TI  - Synthesis of Pt-Cu nanodendrites through controlled reduction kinetics for
      enhanced methanol electro-oxidation.

PMID- 24106044
TI  - Testicular microlithiasis in acquired undescended testis after orchidopexy at
      diagnosis.
AB  - The aim of this study was to observe the prevalence of testicular microlithiasis
      (TM) in surgically corrected acquired undescended testis (UDT). The prevalence of
      TM was assessed by ultrasound. Boys and young men who had undergone orchidopexy
      (ORP) for acquired UDT in mid or late childhood were observed to study the long
      term testicular volume. During this examination, the presence or absence of TM
      was also assessed. TM was defined as echogenic foci without shadowing within the
      testis parenchyma. We included 106 patients who had undergone ORP at the Medical
      Center Alkmaar (1986-1999) and 155 patients who had undergone ORP at the Juliana
      Children's Hospital (1996-2009). The majority of patients were white, Caucasian
      (82%). The median age at follow-up, 25.8 years (range 14.0-31.6 years) was higher
      in Medical Center Alkmaar than in Juliana Children's Hospital 13.4 years (range
      5.1-26.6 years). From 2009 to 2011, these 261 patients (median age 18.9 years)
      underwent an ultrasound examination. Median follow-up after ORP was 11.3 years
      (range 1.4-23.5 years); age at ORP ranged from 2.1 to 16.2 years, with a median
      of 8.5 years. TM was found in 17 (6.5%) patients (median age at follow-up 20.4
      years; range 11-28). No significant association was found with the incidence of
      TM and the operated testis, the age at ORP or the racial variance (p > 0.05). ORP
      at diagnosis for acquired UDT is associated with a 6.5% prevalence of TM in boys
      and young adults. 

PMID- 24106045
TI  - Isolation of a carborane-fused triazole radical anion.
AB  - Outside the cage: A change in the redox properties of a triazole fused to a
      carborane anion through methylation to form a zwitterion enabled facile chemical
      reduction of the compound to an isolable triazole radical anion (see structure: C
      gray, H white, N blue, B brown, Cl green). The radical anion is stabilized by
      kinetic protection by the chlorinated carborane and the delocalization of spin
      density throughout the exo-cluster pi system. 

PMID- 24106046
TI  - Cholesterol modification of (Bio)polymers using UV-Vis traceable chemistry in
      aqueous solutions.
AB  - Cholesterol modification of synthetic and biological polymers is achieved using
      of thiocholesterol (TC) and thiol-disulfide exchange. TC is reacted with Ellman's
      reagent to produce a mixed disulfide (TC-ER) which is activated towards thiol
      disulfide exchange. TC-ER is used to obtain an inclusion complex with methyl-beta
      cyclodextrin, which is then employed to achieve cholesterol functionalization of
      a model peptide, synthetic polymers, and physical hydrogels based on poly(vinyl
      alcohol). It is anticipated that the established techniques will significantly
      broaden the use of cholesterol in bio- and nanotechnology and specifically
      biomedicine. 

PMID- 24106047
TI  - The arteries of brain base in species of Bovini tribe.
AB  - Studies were conducted on 78 preparations of head and brain arteries in four
      species of Bos genus, that is in domestic cattle (N = 59), including 22 foetuses
      (CRL 36.5-78.5 cm), in banteng (Bos javanicus, N = 3), yak (Bos mutus f.
      grunniens, N = 2), American bison (Bison bison, N = 4), and European bison (Bison
      bonasus, N = 10). The comparative analysis permitted to demonstrate a similar
      pattern of brain base arteries in the studied animals. In the studied species,
      blood vessels of the arterial circle of the brain were found to form by
      bifurcation of intracranial segments of inner carotid arteries, which protruded
      from the paired rostral epidural rete mirabile. In Bovidae arterial circle of the
      brain was supplied with blood mainly by maxillary artery through the blood
      vessels of the paired rostral epidural rete mirabile. The unpaired caudal
      epidural rete mirabile was participating in blood supply to the arterial circle
      of the brain from vertebral and occipital arteries. It manifested character of a
      taxonomic trait for species of Bos and Bison genera. Basilar artery in all the
      examined animals manifested a variable diameter, with preliminary portion
      markedly narrowed, which prevented its participation in blood supply to the
      arterial circle of the brain. The results and taxonomic position of the species
      made the authors to suggest a hypothesis that a similar arterial pattern on the
      brain base might be present also in other species, not included in this analysis.

PMID- 24106048
TI  - Anti-citrullinated protein antibodies acquire a pro-inflammatory Fc glycosylation
      phenotype prior to the onset of rheumatoid arthritis.
AB  - OBJECTIVE: To determine whether anticitrullinated protein antibodies (ACPA)
      exhibit specific changes in Fc glycosylation prior to the onset of arthritis.
      METHODS: Serum samples of patients with ACPA-positive arthralgia (n=183) were
      collected at baseline and at various time points of follow-up. 105 patients
      developed arthritis after a median of 12 months (IQR 6-24) and were classified as
      having either rheumatoid arthritis (RA, n=48) or undifferentiated arthritis (UA,
      n=57) based on the 1987 American College of Rheumatology (ACR) criteria. ACPA and
      total serum IgG were isolated by affinity purification and cleaved by trypsin.
      ACPA-IgG1 Fc-glycopeptides were subsequently analysed by nano-liquid
      chromatography mass spectrometry and compared to those of total IgG1. RESULTS: At
      baseline, ACPA-IgG1 and total IgG1 from arthralgia patients displayed similar Fc
      glycosylation patterns. By contrast, at the onset of arthritis, ACPA exhibited a
      decrease in galactose residues in RA patients, but not in UA patients. This
      decrease occurred around 3 months prior to diagnosis and was paralleled by an
      increase in systemic inflammation (erythrocyte sedimentation rate).
      Galactosylation of total IgG1 was also decreased in RA, but this did not precede
      the onset of arthritis. Interestingly, we additionally noted a higher degree of
      ACPA-IgG1 Fc core fucosylation at baseline as compared with total IgG1, which
      further increased prior to diagnosis. CONCLUSIONS: ACPA display significant
      changes in Fc galactosylation and fucosylation prior to the onset of RA. These
      changes towards a more pro-inflammatory phenotype could be involved in driving
      the disease process.

PMID- 24106049
TI  - No evidence for a critical role of the unfolded protein response in synovium and
      blood of patients with ankylosing spondylitis.

PMID- 24106050
TI  - Gadolinium(III) spin labels for high-sensitivity distance measurements in
      transmembrane helices.

PMID- 24106051
TI  - Extraosseous Ewing's sarcoma arising in the perineal region (Rectovaginal
      Septum): a case report with respect to the usefulness of cytological examination.

PMID- 24106052
TI  - An on-line sample pretreatment technique for the HPLC analysis of plant samples.
AB  - A continuous-flow, on-line sample pretreatment technique using a silica gel
      microsyringe extractor has been developed. All steps including extraction,
      separation, clean-up, and concentration occur in the microsyringe. The overall
      sample pretreatment process takes <10 min per sample. Different polarity
      chemicals in the plant sample are successively extracted and separated, and
      analyzed in parallel using HPLC-UV and HPLC-UV-MS/MS. Polycyclic aromatic
      hydrocarbons, alkylphenols, and plant hormones were determined as model compounds
      for nonpolar, intermediate polarity, and polar fractions, respectively. All the
      parameters that influence the extraction and separation efficiency of the
      microsyringe extractor have been optimized and evaluated. Under the optimized
      conditions, recoveries of target compounds ranged from 78.4 to 101.9%, the RSD
      was <12.8% and the square of the correlation coefficient was >0.99. Complex plant
      samples of Sambucus Mandshurica Kitag have been tested using this method.
      Fluorene, phenanthrene, pyrene, and plant hormones were detected in all the
      samples, and concentrations ranged from 24.2-34.9, 43.8-67.1, 25.9-29.2, and
      14.5~110.8 ng/g, respectively.

PMID- 24106053
TI  - Straightforward oxidation of a copper substrate produces an underwater
      superoleophobic mesh for oil/water separation.
AB  - A superhydrophilic and underwater superoleophobic Cu(OH)2-covered mesh with micro
      and nanoscale hierarchical composite structures is successfully fabricated
      through a one-step chemical oxidation of a smooth-copper mesh. Such mesh, without
      any further modification, can selectively separate water from oil/water mixtures
      with high separation efficiency, and possess excellent stability even after 60
      uses. This method provides a simple, low-cost, and scalable strategy for the
      purification of oily wastewater.

PMID- 24106054
TI  - Differences in Clinical Manifestations of Acute and Early HIV-1 Infection between
      HIV-1 Subtypes in African Women.
AB  - Little is known about the differences in clinical manifestations between women
      with various HIV-1 subtypes during acute (AI) and early (EI) HIV infection. In a
      longitudinal cohort study, clinical signs and symptoms among Uganda and Zimbabwe
      women with AI and EI were compared with HIV-negative controls; symptoms were
      assessed quarterly for 15 to 24 months. Early HIV infection was defined as the
      first visit during which a woman tested HIV antibody positive. Women who were HIV
      negative serologically but DNA polymerase chain reaction positive were considered
      AI. In all, 26 women were classified AI and 192 EI, with 654 HIV-negative
      controls. Primary HIV infection (AI and EI) was associated with unexplained fever
      (P <.01), weight loss (P <.01), fatigue (P <.01), inguinal adenopathy (P <.01),
      and cervical friability (P =.01). More women with subtype C infection had
      unexplained fever, fatigue, and abnormal vaginal discharge compared to subtype A
      or D infection. Inguinal adenopathy occurred less often in women with subtype A
      infection than those with subtype C or D infection. 

PMID- 24106055
TI  - Nutritional Status and Other Baseline Predictors of Mortality among HIV-Infected
      Children Initiating Antiretroviral Therapy in Tanzania.
AB  - BACKGROUND: We assembled a prospective cohort of 3144 children less than 15 years
      of age initiating antiretroviral therapy (ART) in Dar es Salaam, Tanzania.
      METHODS: The relationships of nutritional status and other baseline
      characteristics in relation to mortality were examined using Cox proportional
      hazards model. RESULTS: Compared with children with weight for age (WAZ) > -1,
      those with WAZ <= -2 to < -3 had a nearly double risk of death (relative risk
      [RR], 1.85; 95% confidence interval [CI], 1.10-3.11), and among those with WAZ <=
      -3, the risk more than tripled (RR, 3.36; 95% CI, 2.12-5.32). Other baseline risk
      factors for overall mortality included severe anemia (P < .001), severe immune
      suppression (P = .02), history of tuberculosis (P = .01), opportunistic
      infections (P < .001), living in the poorest district (P < .001), and advanced
      World Health Organization stage (P = .003). CONCLUSIONS: To sustain the obtained
      benefit of ART in this setting, interventions to improve nutritional status may
      be used as an adjunct to ART.

PMID- 24106057
TI  - Tipping points in tropical tree cover: linking theory to data.
AB  - It has recently been found that the frequency distribution of remotely sensed
      tree cover in the tropics has three distinct modes, which seem to correspond to
      forest, savanna, and treeless states. This pattern has been suggested to imply
      that these states represent alternative attractors, and that the response of
      these systems to climate change would be characterized by critical transitions
      and hysteresis. Here, we show how this inference is contingent upon mechanisms at
      play. We present a simple dynamical model that can generate three alternative
      tree cover states (forest, savanna, and a treeless state), based on known
      mechanisms, and use this model to simulate patterns of tree cover under different
      scenarios. We use these synthetic data to show that the hysteresis inferred from
      remotely sensed tree cover patterns will be inflated by spatial heterogeneity of
      environmental conditions. On the other hand, we show that the hysteresis inferred
      from satellite data may actually underestimate real hysteresis in response to
      climate change if there exists a positive feedback between regional tree cover
      and precipitation. Our results also indicate that such positive feedback between
      vegetation and climate should cause direct shifts between forest and a treeless
      state (rather than through an intermediate savanna state) to become more likely.
      Finally, we show how directionality of historical change in conditions may bias
      the observed relationship between tree cover and environmental conditions. 

PMID- 24106056
TI  - A novel copper/polydimethiylsiloxane nanocomposite for copper-containing
      intrauterine contraceptive devices.
AB  - In this article, a novel composite of copper (Cu) nanoparticles and
      polydimethiylsiloxane (PDMS) has been prepared and investigated for the potential
      application in Cu-containing intrauterine device. The Cu/PDMS composite with
      various mass fraction of Cu nanoparticles was fabricated via the hot vulcanizing
      process. The chemical structures and surface morphologies of the Cu/PDMS
      composites were characterized confirming the physical interaction between Cu
      nanoparticles and PDMS. The surface morphology observation using scanning
      electron microscope and atomic force microscope showed the agglomeration of Cu
      nanoparticles in PDMS matrix and the distribution of the agglomerations was more
      uniform with increased amount of Cu nanoparticles. The cupric ion release
      behaviors of the Cu/PDMS composites with different amounts of Cu nanoparticles
      were investigated in simulated uterine fluid at 37 degrees C for 150 days. The
      corrosion morphologies of the Cu/PDMS composites were also characterized. Both
      the burst release rate of the cupric ion in the first few days and the steady
      release rate after 30-day immersion were improved. The cytotoxicity test has been
      done for the Cu/PDMS composites.

PMID- 24106058
TI  - Increased levels of hydrogen peroxide and nitric oxide in male partners of
      infertile couples.
AB  - We investigated the prevalence of oxidative stress in male partners of infertile
      couples displaying different inflammation patterns in their genital tract and/or
      oligospermia. The levels of acknowledged oxidative stress markers (8-isoprostanes
      [8-EPI], diene conjugates, reactive oxygen species-total antioxidant capacity
      [ROS-TAC] score) were elevated in both leukocytospermic men and subjects whose
      inflammation was limited only to expressed prostatic secretion and/or post
      massage urine. Oligospermic men with severe inflammation were different from
      oligospermic men who had no inflammation at all - the former had elevated 8-EPI,
      diene conjugates and ROS-TAC score when compared to the latter indicating that
      inflammation has substantially more significant impact on oxidative stress
      markers than oligospermia status. At the same time nitric oxide (NO) and hydrogen
      peroxide (H2 O2 ) levels were significantly increased not only in the men with
      severe inflammation but also in men with borderline inflammation in their genital
      tact and in men having non-inflammatory oligospermia. NO, H2 O2 and 8-EPI were
      negatively correlated with per cent of normal sperms, and NO and H2 O2 showed
      negative correlation also with sperm count. We can conclude that in men
      presenting with couple infertility the acknowledged oxidative stress markers are
      substantially associated with markers of inflammation in genital tract while NO
      and H2 O2 display high levels also in patients with mild inflammation and non
      inflammatory oligospermia. 

PMID- 24106059
TI  - Growth of the human ilium: the anomalous sacroiliac junction.
AB  - Despite the major anatomical importance of the human ilium in medicine and
      forensic investigations, little is understood about its pattern of growth. This
      study was conducted to investigate the changes in the surface area of the human
      ilium from birth through to adolescence in 80 human ilia. A photographic image of
      the pelvic surface of each bone was taken and examined using an image
      quantification package. The surface areas of four regions of interest were
      quantified: the auricular, post-auricular (PA), iliac fossa, and whole pelvic
      surface of the ilium. The results highlight a rapid increase in surface area for
      all regions in the first few years after birth which continues, albeit at a
      slower rate, until ~4 years of age when the rate of growth is further reduced.
      Although the ilium and its various components continue to grow between 5 years
      and puberty, the rate of growth is markedly reduced until puberty when growth of
      the pelvis again increases. Interestingly, analysis of the differential growth of
      the auricular region compared with the PA region throughout development suggests
      that the PA region exhibits more advanced growth. This may indicate that its role
      in structural development for the purposes of preparation and maintenance of
      bipedal stance and locomotion may have been previously poorly understood.

PMID- 24106061
TI  - 3-Silylated cyclohexa-1,4-dienes as precursors for gaseous hydrosilanes: the B(C6
      F5)3-catalyzed transfer hydrosilylation of alkenes.

PMID- 24106060
TI  - Acute eosinophilic pneumonia occurring in a dedicator of cytokinesis 8 (DOCK8)
      deficient patient.
AB  - Dedicator of cytokinesis 8 (DOCK8) deficiency is an autosomal recessive type of
      combined immunodeficiency with elevated IgE. In this report, we describe a
      Japanese girl of non-consanguineous family suffering from acute eosinophilic
      pneumonia (AEP) as a presenting feature of DOCK8 deficiency. Although AEP was
      self-limiting, consecutively experienced recurrent respiratory infections, severe
      atopic dermatitis, and vulnerability to viral infections, prompted us to evaluate
      the possibility of DOCK8 deficiency. Immunological assessments demonstrated
      decreased IgM, increased IgE, T lymphocytepenia, especially in CD4 T cells,
      decreased PHA blastogenesis, and decreased CD27(+) CD19(+) memory B cells.
      Western blotting revealed the absence of DOCK8 protein. Investigation of genomic
      DNA by multiplex ligation-dependent probe amplification (MLPA) revealed a
      heterozygous large deletion of 77 kb spanning from intron 5 to exon 22. DOCK8
      cDNA sequencing revealed a nonsense mutation at position 740 (E740X). As far as
      we know, this is the first Japanese case of DOCK8 deficiency.

PMID- 24106062
TI  - Biomass-derived chemicals: synthesis of biodegradable surfactant ether molecules
      from hydroxymethylfurfural.
AB  - A new class of biodegradable anionic surfactants with structures based on 5
      alkoxymethylfuroate was prepared starting from 5-hydroxymethylfurfural (HMF),
      through a one-pot-two-steps process which involves the selective etherification
      of HMF with fatty alcohols using heterogeneous solid acid, followed by a highly
      selective oxidation of the formyl group with a gold catalyst. The etherification
      step was optimized using aluminosilicates as acid catalysts with different pore
      topologies (H-Beta, HY, Mordenite, ZSM-5, ITQ-2, and MCM-41), different active
      sites (Bronsted or Lewis) and different adsorption properties. It was shown that
      highly hydrophobic defect-free H-Beta zeolites with Si/Al ratios higher than 25
      are excellent acid catalysts to perform the selective etherification of HMF with
      fatty alcohols, avoiding the competitive self-etherification of HMF. Moreover,
      the 5-alkoxymethylfurfural derivatives obtained can be selectively oxidized to
      the corresponding furoic salts in excellent yield using Au/CeO2 as catalyst and
      air as oxidant, at moderated temperatures. Both H-Beta zeolite and Au/CeO2 could
      be reused several times without loss of activity. 

PMID- 24106063
TI  - Isothiourea-mediated one-pot synthesis of functionalized pyridines.
AB  - Acids to bases: The synthesis of 2,4,6-trisubstituted pyridines from
      (phenylthio)acetic acid and a range of alpha,beta-unsaturated ketimines is
      reported. This process proceeds by intermolecular Michael addition/lactamization,
      thiophenol elimination, and N- to O-sulfonyl migration, giving 2-sulfonate
      substituted pyridines which are readily derivatized to generate structural
      diversity. 

PMID- 24106064
TI  - Nanoprobes visualizing gliomas by crossing the blood brain tumor barrier.
AB  - The difficulty in delineating the glioma margins in brain is a major obstacle for
      its completed resection, which leads to the disproportionately high recurrence
      and mortality. Besides the fast exertion rate, inadequate sensitivity and non
      targeting specificity, the main reason leading to failure of small molecular
      probes to define gliomas is their incapability to efficiently cross the blood
      brain tumor barrier (BBTB). Nanoprobes (NPs) show promise to precisely delineate
      the geographically irregular tumor margins due to their tunable size/circulation
      lifetime that maximize their passive intratumoral accumulation and their
      convenience for surface modification that increases the BBTB transcytosis
      efficacy, imaging sensitivity and receptor targeting specificity. In this work,
      the characteristics of the BBTB are addressed from biological and physiological
      perspectives, strategies are presented to deliver NPs across the BBTB, recent
      developments of NPs are reviewed for glioma visualization and finally the
      difficulty and promise for clinical translation of NPs are described. Overall,
      NPs hold great potential for glioma imaging and treatment by pre-surgically
      delineating tumor margins and intra-operatively guiding tumor excision. 

PMID- 24106065
TI  - Effect of linker length and composition on heterobivalent ligand-mediated
      receptor cross-talk between the A1 adenosine and beta2 adrenergic receptors.
AB  - Heterobivalent ligands that possess pharmacophores designed to interact with both
      the A1 adenosine receptor (A1 AR) and the beta2 adrenergic receptor (beta2 AR)
      were prepared. More specifically, these ligands contain an adenosine moiety that
      is linked via its N(6) -position to the amino group of the saligenin-substituted
      ethanolamine moiety present in the well-known beta2 AR agonist, salbutamol. The
      affinities of these ligands were determined at both receptors and found to vary
      with linker length and composition. With all compounds, affinity and functional
      potencies were found to have selectivity for the A1 AR over the beta2 AR. In all
      cases, cAMP accumulation (a beta2 AR-mediated response) was mainly observed when
      the A1 AR was blocked or its function decreased by pertussis toxin or chronic
      agonist treatment. This suggests that heterobivalent compounds for receptors that
      mediate opposite responses might be useful for elucidating the mechanisms of
      receptor cross-talk and how this interaction, in terms of responsiveness, may
      change under pathophysiological conditions. 

PMID- 24106066
TI  - Two-photon solvatochromism II: experimental and theoretical study of solvent
      effects on the two-photon absorption spectrum of Reichardt's dye.
AB  - In this study, we report on the influence of solvent on the two-photon absorption
      (2PA) spectra of Reichardt's dye (RD). The measurement of 2PA cross-sections is
      performed for three solvents (chloroform, dimethyl formamide, and dimethyl
      sulfoxide) using the Z-scan technique. The key finding of this study is the
      observation that the cross-section, corresponding to the 2PA of the
      intramolecular charge-transfer state, diminishes substantially upon increasing
      the solvent polarity. To unravel the solvent dependence of the 2PA cross-section,
      the electronic structure of RD is determined using a hybrid quantum
      mechanics/molecular mechanics (QM/MM) approach, in which polarization between the
      solute and solvent is taken into account by using a self-consistent scheme in the
      solvent polarization. The two-state approximation proves to be adequate for the
      studied system, and allowed the observed solvent-polarity-induced decrease of the
      2PA cross-section to be related to the decrease of the transition moment and the
      increase in the excitation energy. 

PMID- 24106067
TI  - Joint probability of statistical success of multiple phase III trials.
AB  - In drug development, after completion of phase II proof-of-concept trials, the
      sponsor needs to make a go/no-go decision to start expensive phase III trials.
      The probability of statistical success (PoSS) of the phase III trials based on
      data from earlier studies is an important factor in that decision-making process.
      Instead of statistical power, the predictive power of a phase III trial, which
      takes into account the uncertainty in the estimation of treatment effect from
      earlier studies, has been proposed to evaluate the PoSS of a single trial.
      However, regulatory authorities generally require statistical significance in two
      (or more) trials for marketing licensure. We show that the predictive statistics
      of two future trials are statistically correlated through use of the common
      observed data from earlier studies. Thus, the joint predictive power should not
      be evaluated as a simplistic product of the predictive powers of the individual
      trials. We develop the relevant formulae for the appropriate evaluation of the
      joint predictive power and provide numerical examples. Our methodology is further
      extended to the more complex phase III development scenario comprising more than
      two (K > 2) trials, that is, the evaluation of the PoSS of at least k0 (k0<= K)
      trials from a program of K total trials.

PMID- 24106068
TI  - Stimuli-responsive spherical brushes based on D-galactopyranose and 2
      (dimethylamino)ethyl methacrylate.
AB  - Stimuli-responsive spherical brushes composed of 6-O-methacryloyl-1,2:3,4-di-O
      isopropylidene-D-galactopyranose (MAIGal) and 2-(dimethylamino)ethyl methacrylate
      (DMAEMA) are prepared via atom transfer radical polymerization (ATRP) using cross
      linked polystyrene nanoparticles covered with a thin layer of 2-(2
      bromoisobutyryloxy)ethyl methacrylate (BIEM) as ATRP initiator by the "grafting
      from" approach. The stimuli-responsive behavior of the deprotected spherical
      PMAGal-b-PDMAEMA block copolymer brushes is investigated by dynamic light
      scattering and cryogenic transmission electron microscopy. A brush with arms
      containing 160 MAGal and 170 DMAEMA monomer units shows a significant contraction
      of the hydrodynamic radius from 20 to 70  degrees C at pH = 8 with a cloud point
      at ~40  degrees C, whereas no LCST is detected at pH = 6 and 7 due to the
      protonation of the DMAEMA units. Aggregates occur at low temperatures and pH 8
      due to intermolecular interactions between the chains of different brushes, which
      disappear above LCST, when the PDMAEMA chains fold back to the core of the
      brushes, exposing the glycopolymer chains to the outside. 

PMID- 24106069
TI  - HPLC analysis of synthetic polymers on short monolithic columns.
AB  - Ultrashort monolithic columns (disks) were thoroughly studied as efficient
      stationary phases for precipitation-dissolution chromatography of synthetic
      polymers. Gradient elution mode was applied in all chromatographic runs. The
      mixtures of different flexible chain homopolymers, such as polystyrenes,
      poly(methyl methacrylates), and poly(tert-butylmethacrylates) were separated
      according to their molecular weights on both commercial poly(styrene-co
      divinylbenzene) disks (12 id * 3 mm and 5 * 5 mm) and lab-made monolithic columns
      (4.6 id * 50 mm) filled with supports of different hydrophobicity. The
      experimental conditions were optimized to reach fast and highly efficient
      separation. It was observed that, similar to the separation of monoliths of other
      classes of (macro)molecules (proteins, DNA, oligonucleotides), the length of
      column did not affect the peak resolution. A comparison of the retention
      properties of the poly(styrene-co-divinylbenzene) disk-shaped monoliths with
      those based on poly(lauryl methacrylate-co-ethylene dimethacrylate), poly(butyl
      methacrylate-co-ethylene dimethacrylate), and poly(glycidyl methacrylate-co
      ethylene dimethacrylate) supports demonstrated the obvious effect of surface
      chemistry on the resolution factor. Additionally, the results of the discussed
      chromatographic mode on the fast determination of the molecular weights of
      homopolymers used in this study were compared to those established by SEC on
      columns packed with sorbent beads of a similar nature to the monoliths. 

PMID- 24106070
TI  - Exogenous Vasopressin-Induced Hyponatremia in Patients With Vasodilatory Shock:
      Two Case Reports and Literature Review.
AB  - Vasopressin has gained wide support as an adjunct vasopressor in patients with
      septic shock. This agent exerts its vasoconstriction effects through smooth
      muscle V1 receptors and also has antidiuretic activity via renal V2 receptors.
      This interaction with the renal V2 receptors results in the integration of
      aquaporin 2 channels in the apical membrane of the renal collecting duct leading
      to free water reabsorption. Thus, water intoxication with subsequent
      hyponatremia, although rare, is a potentially serious side effect of exogenous
      vasopressin administration. We present 2 patients who developed hyponatremia
      within hours of initiation of vasopressin infusion. Extensive diuresis followed
      its discontinuation with subsequent normalization of serum sodium. One of the
      patients required the use of hypertonic saline for more rapid normalization of
      serum sodium due to concerns for potential seizure activity. A review of the
      literature relevant to the incidence of vasopressin-induced hyponatremia is
      provided as well as discussion on additional factors relevant to septic shock
      that should be considered when determining the relative risk of hyponatremia in
      patients receiving vasopressin. 

PMID- 24106071
TI  - Osteocyte density in the peri-implant bone of implants retrieved after different
      time periods (4 weeks to 27 years).
AB  - Bone tissue is characterized by a constant turnover in response to mechanical
      stimuli, and osteocytes play an essential role in bone mechanical adaptation.
      However, little to no information has been published regarding osteocyte density
      as a function of implantation time in vivo. The aim of this retrospective
      histological study was to evaluate the osteocyte density of the peri-implant bone
      in implants retrieved because of different reasons in a time period from 4 weeks
      to 27 years. A total of 18 samples were included in the present study. Specimens
      were divided into 3 groups depending on the loading history of the implants:
      loading between 4 weeks and 7 months (group 1); loading between 1 and 5 years
      (group 2); loading between 14 and 27 years (group 3). All the samples were
      histologically evaluated and osteocyte density was obtained using the ratio of
      the number of osteocytes to the bone-area (mm(2) ). The osteocyte density values
      significantly increased in the Group 2 (1-5 years) compared with Group 1 (4 weeks
      7 months), and significantly decreased in the Group 3 (14-27 years) compared to
      Group 2. No significant differences were detected between Group 1 and Group 3.
      The decrease in osteocyte density observed in samples that were in vivo for long
      periods of time under loading is possibly because of the fact that once the bone
      structure is well aligned and biomechanically competent, a lower number of
      osteocytes are necessary to keep the tissue homeostasis under loading.

PMID- 24106072
TI  - Sildenafil increases serum testosterone levels by a direct action on the testes.
AB  - Phosphodiesterase-5-inhibitors, such as sildenafil, increase intracavernosal
      cyclic guanosine monophosphate levels, which results in corporal smooth muscle
      relaxation and penile erection. Here, we determined the effects of sildenafil
      administration on the hypothalamic-pituitary-gonadal axis in men with erectile
      dysfunction and low testosterone levels. The Testosterone and Erectile
      Dysfunction trial (ClinicalTrials.gov # NCT00512707) initially administered an
      optimized dose of sildenafil to 140 men, aged 40-70 years with erectile
      dysfunction, low serum total testosterone (<11.4 nmol/L; 330 ng/dL) and/or free
      testosterone (<173 pmol/L; 50 pg/mL) over 3-7 weeks. Sex steroids and
      gonadotropins were measured at baseline and after sildenafil optimization in a
      longitudinal study without a separate control group. Serum testosterone,
      dihydrotestosterone (DHT) and oestrogens were measured using liquid
      chromatography-tandem mass spectrometry. Administration of an optimized dose of
      sildenafil was associated with mean increases of 3.6 nmol/L (103 ng/dL; p <
      0.001) and 110 pmol/L (31.7 pg/mL; p < 0.001) in total and free testosterone
      levels respectively. This was accompanied by parallel increases in serum DHT
      (0.17 nmol/L; 4.9 ng/dL; p < 0.001) and oestradiol (14 pmol/L; 3.7 pg/mL; p <
      0.001) and significant suppression of luteinizing hormone (change -1.3 units/L; p
      = 0.003) levels, suggesting a direct effect at the testicular level.
      Androstenedione and oestrone increased by 1.3 nmol/L (38 ng/dL; p = 0.011) and
      10.7 pmol/L (2.9 pg/mL; p = 0.012), respectively, supporting a possible effect of
      sildenafil on adrenal steroidogenesis. In conclusion, sildenafil administration
      was associated with increased testosterone levels likely ascribable to a direct
      effect on the testis. 

PMID- 24106073
TI  - Relationship between glycated haemoglobin and subclinical atherosclerosis in
      obese children and adolescents.
AB  - OBJECTIVE: To explore the relationship between glycated haemoglobin A1C (HbA1C)
      and subclinical atherosclerosis as assessed by carotid intima-media thickness
      (cIMT) in Chinese Han obese children and adolescents without diabetes. METHODS: A
      total of 524 obese children and adolescents without diabetes were analysed. All
      participants underwent HbA1C measurements, oral glucose tolerance tests and
      ultrasound measurements of cIMT. The logistic regression models were implemented
      to evaluate the adjusted OR of HbA1C for increased cIMT. RESULTS: In obese boys,
      HbA1C was associated with increased cIMT independently of age, measurements of
      anthropometry, blood pressure, plasma lipid and lipoprotein, fasting plasma
      glucose, 2 h postchallenge glucose, uric acid and hepatic function. After
      adjustment for all these risk factors, the OR of increased cIMT for every 1% (11
      mmol/mol) increase in HbA1C was 2.702 (95% CI 1.640 to 4.452). However, in girls,
      the major risk factor independently associated with cIMT was measurement of
      abdominal obesity instead of HbA1C. CONCLUSIONS: Our research suggests that the
      adoption of HbA1C as a diagnostic criterion of prediabetes and diabetes in obese
      boys may help to identify early macrovascular complications.

PMID- 24106074
TI  - Unilateral neuroretinitis secondary to Bartonella henselae infection.

PMID- 24106075
TI  - Angiogenic and tissue remodeling factors in the prostate of elderly rats
      submitted to hormonal replacement.
AB  - The influence of senescence and hormone replacement on the onset of pathologic
      processes in the prostate is not yet fully understood. The aim was to identify
      the immunoreactivity and protein levels of molecules involved in cell
      proliferation, tissue remodeling and angiogenesis in the ventral prostate of
      elderly rodents following hormonal replacement. Male Sprague-Dawley rats were
      separated into one Young group (4-months old), treated with peanut oil (5 mL kg(
      1) , s.c.), and six Senile groups. The senile rats (10-months old) were
      subdivided into: Senile group (SEN) (5 mL kg(-1) peanut oil, s.c.); Testosterone
      group (TEST) (5 mg kg(-1) testosterone cipionate, s.c.); Estrogen group (EST) (25
      ug kg(-1) 17beta-estradiol, s.c.); castrated group (CAS) (surgical castration);
      castrated-testosterone group (CT) (same treatment as CAS and TEST groups); and
      castrated-estrogen group (CE) (same treatment as CAS and EST groups). After 30
      days, samples of the ventral prostate were harvested for analyses of insulin-like
      growth factor-1 receptor (IGFR-1), matrix metalloproteinase-9 (MMP-9), vascular
      endothelial growth factor (VEGF) and endostatin features. IGFR-1 and MMP-9 showed
      increased protein levels and epithelial immunolabeling both after hormonal
      replacement and castration. Increased VEGF levels and reduced endostatin were
      verified in the SEN group. Hormonal therapy and castration led to a higher
      increase of VEGF, especially in the EST, CAS, and CE groups. Endostatin increased
      mainly in the TEST and CT groups. Hormonal therapy in senescence generated a
      reactive microenvironment characterized by the increase of mitogenic and tissue
      remodeling factors and by the imbalance of angiogenesis, which possibly
      compromised organ function and predisposed toward glandular disorders.

PMID- 24106076
TI  - Playing with structures at the nanoscale: designing catalysts by manipulation of
      clusters and nanocrystals as building blocks.
AB  - The purpose of this Concept is to highlight some of the most recent and promising
      methods for the preparation of tailored catalysts by designing and preparing the
      component building blocks and by assembling them in a controlled fashion. We want
      to emphasize how rational design and synthesis of catalysts must be coupled to
      precise catalytic and structural characterization of the systems in an ideal
      feedback loop. New catalyst design and preparation techniques, dictated by
      information about the active sites that the specific application requires, are
      frequently available. The building blocks for developing these novel catalysts
      include colloidal methods for the preparation of uniform nanostructures, physical
      methods for rational assembly of the building blocks (Langmuir-Blodgett, liquid
      air self-assembly), and development of rational interactions between the building
      blocks for enhanced activity of the assemblies. These methods, which apply
      techniques normally used in other fields of nanotechnology to catalysis, offer
      exciting opportunities to help improve currently available catalytic systems in
      terms of activity, stability and selectivity. 

PMID- 24106077
TI  - Discovery and biological characterization of the auromomycin chromophore as an
      inhibitor of biofilm formation in Vibrio cholerae.
AB  - Bacterial biofilms pose a significant challenge in clinical environments due to
      their inherent lack of susceptibility to antibiotic treatment. It is widely
      recognized that most pathogenic bacterial strains in the clinical setting persist
      in the biofilm state, and are the root cause of many recrudescent infections. The
      discovery and development of compounds capable of either inhibiting biofilm
      formation or initiating biofilm dispersal might provide new therapeutic avenues
      for reducing the number of hospital-acquired, biofilm-mediated infections. We
      detail here the application of our recently reported image-based, high-throughput
      screen to the discovery of microbially derived natural products with inhibitory
      activity against Vibrio cholerae biofilm. Examination of a prefractionated
      library of microbially derived marine natural products has led to the
      identification of a new biofilm inhibitor that is structurally unrelated to
      previously reported inhibitors and is one of the most potent inhibitors of V.
      cholerae reported to date. Combination of this compound with sub-MIC
      concentrations of a number of clinically relevant antibiotics was shown to
      improve the inhibitory efficacy of this new compound compared to monotherapy
      treatments, and provides evidence for the potential therapeutic benefit of
      biofilm inhibitors in treating persistent biofilm-mediated infections. 

PMID- 24106078
TI  - Electrochemical properties of yolk-shell-structured CuO-Fe(2)O(3) powders with
      various Cu/Fe molar ratios prepared by one-pot spray pyrolysis.
AB  - Several yolk-shell-structured CuO-Fe2 O3 powders with various Cu/Fe molar ratios
      have been successfully prepared under equivalent reaction conditions using a one
      pot spray pyrolysis process. The Cu and Fe components are uniformly distributed
      throughout the powders, irrespective of composition. The Brunauer-Emmett-Teller
      surface areas of the yolk-shell CuO-Fe2 O3 systems increased from 5 to 16 m(2) 
      g(-1) if the Cu/Fe molar ratios are decreased from 3:1 to 1:3. The initial
      discharge and charge capacities of the yolk-shell CuO-Fe2 O3 system (Cu/Fe=1:2),
      showing maximum values at a constant current density of 1000 mA g(-1) , are 1436
      and 1012 mA h g(-1) , respectively. After 130 cycles, the discharge capacities of
      the yolk-shell CuO-Fe2 O3 powders with Cu/Fe molar ratios of 1:3, 1:2, 1:1, 2:1,
      and 3:1 are 1159, 1151, 755, 655, and 651 mA h g(-1) , respectively. The
      discharge capacities of the yolk-shell and dense powder samples after 50 cycles,
      when subjected to a series of current density increases from 500 to 5000 mA g(-1)
      , are 735 and 495 mA h g(-1) , respectively. 

PMID- 24106080
TI  - Direct delamination of graphene for high-performance plastic electronics.
AB  - Electrochemical delamination is developed to transfer graphene for plastic
      electronics. The use of a sacrificial support during transfer is eliminated by
      depositing the target polyimide substrate directly onto graphene. A continuous
      and residue-free graphene surface with less line disruptions (such as ripples and
      wrinkles) is obtained on the target polyimide substrate, and good mechanical
      durability as well as low sheet resistance is obtained. The properties are
      competitive with conventional transparent conducting films. 

PMID- 24106079
TI  - Surface tension of airway aspirates withdrawn during neonatal resuscitation
      reflects lung maturity.
AB  - The indications for treatment of neonates with exogenous pulmonary surfactant are
      still discussed controversially. Some premature neonates are sufficiently treated
      by CPAP, others need conventional ventilation and/or surfactant. The available
      lung maturity tests have limitations. The captive bubble surfactometer (CBS)
      provides measurement of surface activity from rather small amounts of surfactant.
      This study aimed to determine surface activity from small volume aspirates of the
      upper airways of neonates by means of the CBS and to correlate the results with
      clinical data. Small upper airway aspirates from 159 neonates (gestational age 25
      42 weeks) were withdrawn and concentrated 16.7-fold by ultracentrifugation and
      resuspension in saline. Surface activities after 5 min of adsorption were
      determined in the CBS and correlated to the perinatal data (e.g., gestational
      age, birth weight, gender), airway interventions (like CPAP, conventional
      ventilation) and surfactant treatment. Additionally, 27 samples were analyzed for
      surfactant specific phosphatidylcholine concentrations by using electrospray
      ionization tandem mass-spectroscopy. Surface activities show a significant
      correlation to gestational age, birth weight, and the need for airway
      interventions. Comparing the need for airway interventions versus surface
      activity, a receiver operating characteristic calculated a sensitivity of 0.77
      and a specificity of 0.72 at a "cut off" of 44 mN/m. Surface activity correlates
      significantly with the phosphatidylcholine concentrations and the latter one
      correlates with the gestational age. Determination of surface activity from upper
      airway aspirates is feasible. Further clinical studies are needed to prove the
      predictive value of the method.

PMID- 24106081
TI  - Sigma-2 receptor agonists as possible antitumor agents in resistant tumors: hints
      for collateral sensitivity.
AB  - With the aim of contributing to the development of novel antitumor agents, high
      affinity sigma2 receptor agonists were developed, with 6,7-dimethoxy-2-[4-[1-(4
      fluorophenyl)-1H-indol-3-yl]butyl]-1,2,3,4-tetrahydroisoquinoline (15) and 9-[4
      (6,7-dimethoxy-1,2,3,4-tetrahydroisoquinolin-2-yl)butyl]-9H-carbazole (25)
      showing exceptional selectivity for the sigma2 subtype. Most of the compounds
      displayed notable antiproliferative activity in human MCF7 breast adenocarcinoma
      cells, with similar activity in the corresponding doxorubicin-resistant MCF7adr
      cell line. Surprisingly, a few compounds, including 25, displayed enhanced
      activity in MCF7adr cells over parent cells, recalling the phenomenon of
      collateral sensitivity, which is under study for the treatment of drug-resistant
      tumors. All of the compounds showed interaction with P-glycoprotein (P-gp), and
      15 and 25, with the greatest activity, were able to revert P-gp-mediated
      resistance and reestablish the antitumor effect of doxorubicin in MCF7adr cells.
      We therefore identified a series of sigma2 receptor agonists endowed with
      intriguing antitumor properties; these compounds deserve further investigation
      for the development of alternate strategies against multidrug- resistant cancers.

PMID- 24106082
TI  - Liquid chromatographic resolution of racemic rasagiline and its analogues on a
      chiral stationary phase based on (+)-(18-crown-6)-2,3,11,12-tetracarboxylic acid.
AB  - A liquid chromatographic chiral stationary phase based on (+)-(18-crown-6)
      2,3,11,12-tetracarboxylic acid was applied to the resolution of 15 analytes,
      including racemic rasagiline, a chiral drug for the treatment of Parkinson's
      disease, and its analogues. The composition of mobile phase was optimized to be
      ethanol/acetonitrile/acetic acid/triethylamine (80:20:0.2:0.3, v/v/v/v) by
      evaluating the chromatographic results for the resolution of five selected
      analytes under various mobile phase conditions. Under the optimized mobile phase
      conditions, racemic rasagiline was resolved quite well with a separation factor
      of 1.48 and resolution of 2.71 and its 14 analogues were also resolved reasonably
      well with separation factors of 1.06-1.54 and resolutions of 0.54-2.11. Among 15
      analytes, racemic rasagiline was resolved best except for just one analyte. The
      analyte structure-enantioselectivity relationship indicated that racemic
      rasagiline has the most appropriate structural characteristics for resolution on
      the chiral stationary phase. 

PMID- 24106083
TI  - Bayesian analysis for nonlinear mixed-effects models under heavy-tailed
      distributions.
AB  - A common assumption in nonlinear mixed-effects models is the normality of both
      random effects and within-subject errors. However, such assumptions make
      inferences vulnerable to the presence of outliers. More flexible distributions
      are therefore necessary for modeling both sources of variability in this class of
      models. In the present paper, I consider an extension of the nonlinear mixed
      effects models in which random effects and within-subject errors are assumed to
      be distributed according to a rich class of parametric models that are often used
      for robust inference. The class of distributions I consider is the scale mixture
      of multivariate normal distributions that consist of a wide range of symmetric
      and continuous distributions. This class includes heavy-tailed multivariate
      distributions, such as the Student's t and slash and contaminated normal. With
      the scale mixture of multivariate normal distributions, robustification is
      achieved from the tail behavior of the different distributions. A Bayesian
      framework is adopted, and MCMC is used to carry out posterior analysis. Model
      comparison using different criteria was considered. The procedures are
      illustrated using a real dataset from a pharmacokinetic study. I contrast results
      from the normal and robust models and show how the implementation can be used to
      detect outliers.

PMID- 24106084
TI  - Intrinsically disordered regions of nucleophosmin/B23 regulate its RNA binding
      activity through their inter- and intra-molecular association.
AB  - Nucleophosmin (NPM1/B23) is a nucleolar protein implicated in growth-associated
      functions, in which the RNA binding activity of B23 plays essential roles in
      ribosome biogenesis. The C-terminal globular domain (CTD) of B23 has been
      believed to be the RNA binding domain because the splicing variant B23.2 lacking
      the CTD binds considerably less efficiently to RNA. However, the recognition of
      target RNAs by B23 remains poorly understood. Herein, we report a novel mechanism
      by which B23 recognizes specific RNA targets. We observed that the nucleolar
      retention of B23.3 lacking the basic region of B23.1 was lower than that of B23.1
      because of its low RNA binding activity. Circular dichroism measurements
      indicated that the basic region and adjacent acidic regions of B23 are
      intrinsically disordered regions (IDRs). Biochemical analyses revealed that the
      basic IDR alone strongly binds to RNA with low specificity. The excessive RNA
      binding activity of the basic IDR was restrained by intra-molecular interaction
      with the acidic IDR of B23. Chemical cross-linking experiments and fluorescent
      labeling of bipartite tetracysteine-tagged proteins suggested that the inter- and
      intra-molecular interactions between the two IDRs contribute to the regulation of
      the RNA binding activity of CTD to control the cellular localization and
      functions of B23. 

PMID- 24106085
TI  - Quadruplex-forming sequences occupy discrete regions inside plant LTR
      retrotransposons.
AB  - Retrotransposons with long terminal repeats (LTR) form a significant proportion
      of eukaryotic genomes, especially in plants. They have gag and pol genes and
      several regulatory regions necessary for transcription and reverse transcription.
      We searched for potential quadruplex-forming sequences (PQSs) and potential
      triplex-forming sequences (PTSs) in 18 377 full-length LTR retrotransposons
      collected from 21 plant species. We found that PQSs were often located in LTRs,
      both upstream and downstream of promoters from which the whole retrotransposon is
      transcribed. Upstream-located guanine PQSs were dominant in the minus DNA strand,
      whereas downstream-located guanine PQSs prevailed in the plus strand, indicating
      their role both at transcriptional and post-transcriptional levels. Our circular
      dichroism spectroscopy measurements confirmed that these PQSs readily adopted
      guanine quadruplex structures-some of them were paralell-stranded, while others
      were anti-parallel-stranded. The PQS often formed doublets at a mutual distance
      of up to 400 bp. PTSs were most abundant in 3'UTR (but were also present in
      5'UTR). We discuss the potential role of quadruplexes and triplexes as the
      regulators of various processes participating in LTR retrotransposon life cycle
      and as potential recombination sites during post-insertional retrotransposon
      based genome rearrangements. 

PMID- 24106086
TI  - Tyrosine phosphorylation of HuR by JAK3 triggers dissociation and degradation of
      HuR target mRNAs.
AB  - In response to stress conditions, many mammalian mRNAs accumulate in stress
      granules (SGs) together with numerous RNA-binding proteins that control mRNA
      turnover and translation. However, the signaling cascades that modulate the
      presence of ribonucleoprotein (RNP) complexes in SGs are poorly understood. Here,
      we investigated the localization of human antigen R (HuR), an mRNA-stabilizing
      RNA-binding protein, in SGs following exposure to the stress agent arsenite.
      Unexpectedly, the mobilization of HuR to SGs was prevented through the activation
      of Janus kinase 3 (JAK3) by the vitamin K3 analog menadione. JAK3 phosphorylated
      HuR at tyrosine 200, in turn inhibiting HuR localization in SGs, reducing HuR
      interaction with targets SIRT1 and VHL mRNAs, and accelerating target mRNA decay.
      Our findings indicate that HuR is tyrosine-phosphorylated by JAK3, and link this
      modification to HuR subcytoplasmic localization and to the fate of HuR target
      mRNAs. 

PMID- 24106087
TI  - Compositional and structural analysis of selected chromosomal domains from
      Saccharomyces cerevisiae.
AB  - Chromatin is the template for replication and transcription in the eukaryotic
      nucleus, which needs to be defined in composition and structure before these
      processes can be fully understood. We report an isolation protocol for the
      targeted purification of specific genomic regions in their native chromatin
      context from Saccharomyces cerevisiae. Subdomains of the multicopy ribosomal DNA
      locus containing transcription units of RNA polymerases I, II or III or an
      autonomous replication sequence were independently purified in sufficient amounts
      and purity to analyze protein composition and histone modifications by mass
      spectrometry. We present and discuss the proteomic data sets obtained for
      chromatin in different functional states. The native chromatin was further
      amenable to electron microscopy analysis yielding information about nucleosome
      occupancy and positioning at the single-molecule level. We also provide evidence
      that chromatin from virtually every single copy genomic locus of interest can be
      purified and analyzed by this technique. 

PMID- 24106088
TI  - Regions outside the DNA-binding domain are critical for proper in vivo
      specificity of an archetypal zinc finger transcription factor.
AB  - Transcription factors (TFs) are often regarded as being composed of a DNA-binding
      domain (DBD) and a functional domain. The two domains are considered separable
      and autonomous, with the DBD directing the factor to its target genes and the
      functional domain imparting transcriptional regulation. We examined an archetypal
      zinc finger (ZF) TF, Kruppel-like factor 3 with an N-terminal domain that binds
      the corepressor CtBP and a DBD composed of three ZFs at its C-terminus. We
      established a system to compare the genomic occupancy profile of wild-type
      Kruppel-like factor 3 with two mutants affecting the N-terminal functional
      domain: a mutant unable to contact the cofactor CtBP and a mutant lacking the
      entire N-terminal domain, but retaining the ZFs intact. Chromatin
      immunoprecipitation followed by sequencing was used to assess binding across the
      genome in murine embryonic fibroblasts. Unexpectedly, we observe that mutations
      in the N-terminal domain generally reduced binding, but there were also instances
      where binding was retained or even increased. These results provide a clear
      demonstration that the correct localization of TFs to their target genes is not
      solely dependent on their DNA-contact domains. This informs our understanding of
      how TFs operate and is of relevance to the design of artificial ZF proteins. 

PMID- 24106090
TI  - Laminin-database v.2.0: an update on laminins in health and neuromuscular
      disorders.
AB  - The laminin (LM)-database, hosted at http://www.lm.lncc.br, was published in the
      NAR database 2011 edition. It was the first database that provided comprehensive
      information concerning a non-collagenous family of extracellular matrix proteins,
      the LMs. In its first version, this database contained a large amount of
      information concerning LMs related to health and disease, with particular
      emphasis on the haemopoietic system. Users can easily access several tabs for LMs
      and LM-related molecules, as well as LM nomenclatures and direct links to PubMed.
      The LM-database version 2.0 integrates data from several publications to achieve
      a more comprehensive knowledge of LMs in health and disease. The novel features
      include the addition of two new tabs, 'Neuromuscular Disorders' and 'miRNA--LM
      Relationship'. More specifically, in this updated version, an expanding set of
      data has been displayed concerning the role of LMs in neuromuscular and
      neurodegenerative diseases, as well as the putative involvement of microRNAs.
      Given the importance of LMs in several biological processes, such as cell
      adhesion, proliferation, differentiation, migration and cell death, this upgraded
      version expands for users a panoply of information, regarding complex molecular
      circuitries that involve LMs in health and disease, including neuromuscular and
      neurodegenerative disorders. 

PMID- 24106089
TI  - Comprehensive analysis of DNA polymerase III alpha subunits and their homologs in
      bacterial genomes.
AB  - The analysis of ~ 2000 bacterial genomes revealed that they all, without a single
      exception, encode one or more DNA polymerase III alpha-subunit (PolIIIalpha)
      homologs. Classified into C-family of DNA polymerases they come in two major
      forms, PolC and DnaE, related by ancient duplication. While PolC represents an
      evolutionary compact group, DnaE can be further subdivided into at least three
      groups (DnaE1-3). We performed an extensive analysis of various sequence,
      structure and surface properties of all four polymerase groups. Our analysis
      suggests a specific evolutionary pathway leading to PolC and DnaE from the last
      common ancestor and reveals important differences between extant polymerase
      groups. Among them, DnaE1 and PolC show the highest conservation of the analyzed
      properties. DnaE3 polymerases apparently represent an 'impaired' version of
      DnaE1. Nonessential DnaE2 polymerases, typical for oxygen-using bacteria with
      large GC-rich genomes, have a number of features in common with DnaE3
      polymerases. The analysis of polymerase distribution in genomes revealed three
      major combinations: DnaE1 either alone or accompanied by one or more DnaE2s, PolC
      + DnaE3 and PolC + DnaE1. The first two combinations are present in Escherichia
      coli and Bacillus subtilis, respectively. The third one (PolC + DnaE1), found in
      Clostridia, represents a novel, so far experimentally uncharacterized, set.

PMID- 24106091
TI  - Small interfering RNA nunchucks with a hydrophobic linker for efficient
      intracellular delivery.
AB  - The high stiffness and low spatial charge density of siRNA limit the
      effectiveness of the electrostatic condensation of siRNA with cationic
      polyelectrolytes. Here, a facile method to stabilize nanoscale
      siRNA/polyelectrolyte complexes by introducing a reductively cleavable alkyl
      chain to siRNA as a hybrophobic linker of dimeric siRNA conjugates is reported.
      The increased length of the hydrophobic linker increases the intracellular
      translocation and gene silencing activity of the dimeric siRNA conjugates when
      they are complexed with linear polyethylenimine (LPEI). The results suggest that
      the introduction of a hydrophobic linker in the dimeric siRNA conjugates can
      facilitate the intracellular delivery of siRNA through effective condensation
      with cationic polyelectrolytes. 

PMID- 24106092
TI  - Obstructive sleep apnoea in obese adolescents and cardiometabolic risk markers.
AB  - WHAT IS ALREADY KNOWN ABOUT THIS SUBJECT: In paediatric patients, obstructive
      sleep apnoea is associated with adiposity, especially visceral adiposity. In
      adults, obstructive sleep apnoea is also associated with a higher prevalence of
      cardiovascular disease and type 2 diabetes. There are limited and conflicting
      paediatric studies examining the association between obstructive sleep apnoea and
      biomarkers of risk for cardiovascular disease and type 2 diabetes in youth. WHAT
      THIS STUDY ADDS: Obstructive sleep apnoea is linked with greater cardiometabolic
      risk markers in obese adolescents. Fasting insulin and homeostasis model
      assessment-insulin resistance may be especially linked with obstructive sleep
      apnoea among obese male Hispanic adolescents. The relationship between
      obstructive sleep apnoea and cardiometabolic abnormalities in obese adolescents
      should be considered when evaluating patients found to have obstructive sleep
      apnoea. BACKGROUND: Paediatric studies examining the association between
      obstructive sleep apnoea (OSA) and insulin sensitivity/cardiometabolic risk are
      limited and conflicting. OBJECTIVE: This study aims to determine if
      cardiometabolic risk markers are increased among obese youth with obstructive
      sleep apnoea as compared with their equally obese peers without OSA. METHODS: We
      performed a retrospective analysis of 96 patients (age 14.2 +/- 1.4 years) who
      underwent polysomnography for suspected OSA. Fasting lipids, glucose, insulin and
      haemoglobin A1 c (HbA1 c) were performed as part of routine clinical evaluation.
      Patients were categorized into two groups by degree of OSA as measured by the
      apnoea-hypopnoea index (AHI): none or mild OSA (AHI < 5) and moderate or severe
      OSA (AHI >= 5). RESULTS: Despite the similar degrees of obesity, patients with
      moderate or severe OSA had higher fasting insulin (P = 0.037) and homeostasis
      model assessment-insulin resistance (HOMA-IR [P = 0.0497]) as compared with those
      with mild or no OSA. After controlling for body mass index, there was a positive
      association between the AHI and log HOMA-IR (P = 0.005). There was a positive
      relationship between arousals plus awakenings during the polysomnography and
      fasting triglycerides. CONCLUSIONS: OSA is linked with greater cardiometabolic
      risk markers in obese youth.

PMID- 24106094
TI  - Three-dimensional corrective osteotomy using a patient-specific osteotomy guide
      and bone plate based on a computer simulation system: accuracy analysis in a
      cadaver study.
AB  - BACKGROUND: The accuracy of three-dimensional (3-D) corrective osteotomy using a
      patient-specific osteotomy guide and bone plate based on computer simulation was
      investigated. METHODS: Six fresh-frozen cadaver upper limbs were used. A patient
      specific osteotomy guide designed to realize a preplanned osteotomy was set on
      the distal humerus and distal radius, and the error in the setting location was
      evaluated. After the osteotomy, the surgical site was fixed using a patient
      specific bone plate designed to exactly fit the anatomical shape of the
      postoperative bone model. The postoperative results were compared with the
      preoperative simulation. RESULTS: The errors in the guide location on the humerus
      and radius were <1.5 degrees  and 1.0 mm and <1.0 degrees  and 1.0 mm,
      respectively. The plate fixation errors of the humerus and radius were <2.0
      degrees  and 1.5 mm and <1.0 degrees  and 1.0 mm, respectively. CONCLUSIONS: The
      system is sufficiently feasible to realize precise 3-D deformity correction of a
      limb.

PMID- 24106093
TI  - Three-dimensional configuration of orientated fibers as guidance structures for
      cell migration and axonal growth.
AB  - Peripheral nerve injuries can be surgically repaired by suturing the transected
      nerve stumps or, in case of larger lesions, by the transplantation of an
      autologous nerve graft. To avoid donor site morbidity, the development of
      artificial implants is desired. Clinically, hollow conduits have been used for
      this purpose but are inferior to the autograft because they lack internal
      guidance cues for Schwann cells and regenerating axons. In this article, we
      describe the design of a three-dimensional (3D) scaffold consisting of parallel
      fibers embedded in a collagen matrix. For this purpose, an electrospinning device
      was developed to produce and manipulate a 3D array of aligned poly(E
      caprolactone) (PCL) microfibers. This fiber array was then incorporated into
      biodegradable PCL tubes to serve as artificial nerve bridges. Using primary
      cultures of embryonic chicken dorsal root ganglia, we show that PCL microfibers
      in the 3D matrix of our composite scaffold guide the direction of Schwann cell
      migration and axonal growth.

PMID- 24106095
TI  - Evaluation of UDP-GlcN derivatives for selective labeling of 5
      (hydroxymethyl)cytosine.
AB  - 5-(hydroxymethyl)cytosine (5-hmC) is a newly identified oxidative product of 5
      methylcytosine (5-mC) in the mammalian genome, and is believed to be an important
      epigenetic marker influencing a variety of biological processes. In addition to
      its relatively low abundance, the fluctuation of 5-hmC levels over time during
      cell development poses a formidable challenge for its accurate mapping and
      quantification. Here we describe a specific chemoenzymatic approach to 5-hmC
      detection in DNA samples by using new uridine 5'-diphosphoglucosamine (UDP-GlcN)
      probes. Our approach requires modification of the glucose moiety of UDP-Glc with
      small amino groups and transfer of these glucose derivatives to the hydroxy
      moiety of 5-hmC by using T4 phage glucosyltransferases. We evaluated the transfer
      efficiencies of three glucosyltransferases (wild-type alpha- and beta-GTs and a
      Y261L mutant beta-GT) with five different UDP-Glc derivatives containing
      functionalized groups for subsequent bioconjugation and detection. Our results
      indicate that UDP-6-N3 -Glc, UDP-6-GlcN, and UDP-2-GlcN can be transferred by
      beta-GT with efficiencies similar to that seen with the native UDP-Glc cofactor.
      6-N3 -Glc- and 6-GlcN-containing oligonucleotides were selectively labeled with
      reactive fluorescent probes. In addition, a 2 kb DNA fragment modified with 2
      GlcN groups was specifically detected by use of a commercially available
      antiglucosamine antibody. Alternative substrates for beta-GT and correlated
      glycosyltransferases might prove useful for the study of the function and
      dynamics of 5-hmC and other modified nucleotides, as well as for multiplex
      analysis. 

PMID- 24106096
TI  - Prognostic significance of a positive axillary lymph node fine-needle aspirate in
      patients with invasive breast carcinoma.
AB  - BACKGROUND: Image-guided axillary lymph node fine-needle aspirates (FNAs)
      correlate well with pathologic lymph node staging in cases of invasive breast
      carcinoma. The objective of this study was to determine the prognostic
      significance of a positive lymph node. METHODS: Consecutive cases of
      nonmetastatic (M0) invasive breast carcinoma evaluated by image-guided FNA were
      identified (4-year period, median follow-up of 51 months). "Positive" and
      "nonpositive" groups were compared using Kaplan-Meier survival analysis.
      Multivariate Cox regression was used to correct for clinicopathologic and
      treatment factors. A total of 142 cases was included, 70 with positive axillary
      FNA and 72 with a nonpositive result. RESULTS: FNA-positive and nonpositive cases
      did not differ in patient age, tumor subtype, or hormone receptor status.
      Positive FNA was significantly associated with advanced T and N pathologic stage,
      and with HER2 (human epidermal growth factor receptor 2) positivity. FNA-positive
      patients were more likely to undergo mastectomy and to receive chemotherapy.
      Kaplan-Meier analysis showed that positive FNA is associated with poor prognosis,
      both with respect to disease-free survival (89% nonpositive versus 73% positive
      at 5 years, P < .001) and overall survival (94% versus 81%, respectively, at 5
      years, P = .01). Multivariate analysis showed that when correcting for other
      variables, FNA positivity was not independently significant. CONCLUSIONS:
      Positive axillary lymph node FNA is associated with poor prognosis on univariate
      analysis. By contrast, overall nodal staging is independently significant on
      multivariate analysis. The prognostic significance of axillary FNA likely results
      from its ability to predict for nodal status. Axillary FNA has utility as a
      preoperative staging procedure.

PMID- 24106097
TI  - A glutathione derivative with chelating and in vitro neuroprotective activities:
      synthesis, physicochemical properties, and biological evaluation.
AB  - Metal-ion dysregulation and oxidative stress have been linked to the progressive
      neurological decline associated with neurodegenerative disorders such as
      Alzheimer's and Parkinson's diseases. Herein we report the synthesis and
      chelating, antioxidant, and in vitro neuroprotective activities of a novel
      derivative of glutathione, GS(HQ)H, endowed with an 8-hydroxyquinoline group as a
      metal-chelating moiety. In vitro results showed that GS(HQ)H may be stable enough
      to be absorbed unmodified and arrive intact to the blood-brain barrier, that it
      may be able to remove Cu(II) and Zn(II) from the Abeta peptide without causing
      any copper or zinc depletion in vivo, and that it protects SHSY-5Y human
      neuroblastoma cells against H2 O2 - and 6-OHDA-induced damage. Together, these
      findings suggest that GS(HQ)H could be a potential neuroprotective agent for the
      treatment of neurodegenerative diseases in which a lack of metal homeostasis has
      been reported as a key factor. 

PMID- 24106098
TI  - Laser heating tunability by off-resonant irradiation of gold nanoparticles.
AB  - Temperature changes in the vicinity of a single absorptive nanostructure caused
      by local heating have strong implications in technologies such as integrated
      electronics or biomedicine. Herein, the temperature changes in the vicinity of a
      single optically trapped spherical Au nanoparticle encapsulated in a thermo
      responsive poly(N-isopropylacrylamide) shell (Au@pNIPAM) are studied in detail.
      Individual beads are trapped in a counter-propagating optical tweezers setup at
      various laser powers, which allows the overall particle size to be tuned through
      the phase transition of the thermo-responsive shell. The experimentally obtained
      sizes measured at different irradiation powers are compared with average size
      values obtained by dynamic light scattering (DLS) from an ensemble of beads at
      different temperatures. The size range and the tendency to shrink upon increasing
      the laser power in the optical trap or by increasing the temperature for DLS
      agree with reasonable accuracy for both approaches. Discrepancies are evaluated
      by means of simple models accounting for variations in the thermal conductivity
      of the polymer, the viscosity of the aqueous solution and the absorption cross
      section of the coated Au nanoparticle. These results show that these parameters
      must be taken into account when considering local laser heating experiments in
      aqueous solution at the nanoscale. Analysis of the stability of the Au@pNIPAM
      particles in the trap is also theoretically carried out for different particle
      sizes.

PMID- 24106099
TI  - Analysis of the traditional medicine YiGan San by the fragmentation patterns of
      cadambine indole alkaloids using HPLC coupled with high-resolution MS.
AB  - YiGan San (YGS) has long been used in traditional Japanese and Chinese folk
      medicine and serves as a potent and novel therapeutic agent to treat Alzheimer's
      disease. In the present study, a rapid and sensitive method based on HPLC coupled
      with diode-array detection and quadrupole TOF MS (Q-TOF-MS) was designed to
      reveal the chemical constituents of YGS. Thirty-six compounds were identified and
      assigned in YGS, including 14 alkaloids, nine gamma-lactones, six flavonoids,
      three triterpenoid saponinares, two small molecular organic acids, and two other
      types of compounds. In addition, the accurate fragment weight and MS/MS
      fragmentation reactions of a subtype indole alkaloid in Uncariae ramulus cum
      uncis were summarized for the first time to realize rapid identification without
      reference substances. For the first time, 11 major constituents were
      comprehensively quantified with a HPLC coupled with triple-quadrupole MS method.
      A three-section switch was used to realize such multicomponent identification.
      The contents of saikosaponin B2 and isoliquiritin, which produce anti
      inflammatory and antidepressant-like effects, were extremely different, up to 700
      times, in two sources of YGS. The developed qualitative and quantitative method
      was proved to be precise, accurate, and reproducible. 

PMID- 24106100
TI  - Genetic and functional genomics approaches targeting the Notch pathway in cardiac
      development and congenital heart disease.
AB  - The Notch signalling pathway plays crucial roles in cardiac development and
      postnatal cardiac homoeostasis. Gain- and loss-of-function approaches indicate
      that Notch promotes or inhibits cardiogenesis in a stage-dependent manner.
      However, the molecular mechanisms are poorly defined because many downstream
      effectors remain to be identified. Genome-scale analyses are shedding light on
      the genes that are regulated by Notch signalling and the mechanisms underlying
      this regulation. We review the functional data that implicates Notch in cardiac
      morphogenetic processes and expression profiling studies that enlighten the
      regulatory networks behind them. A recurring theme is that Notch cross-talks
      reiteratively with other key signalling pathways including Wnt and Bmp to
      coordinate cell and tissue interactions during cardiogenesis. 

PMID- 24106102
TI  - Ribosomal protein S5e is implicated in translation initiation through its
      interaction with the N-terminal domain of initiation factor eIF2alpha.
AB  - A key step of translation initiation in eukaryotes is formation of the 48S
      preinitiation complex (PIC) containing the 40S ribosome, a set of eukaryotic
      initiation factors (eIFs), mRNA, and initiator Met-tRNA interacting with mRNA
      start codon; however, the PIC structure remains substantially unknown. Here, we
      apply formaldehyde-induced protein-protein crosslinks to identify contacts
      between ribosomal protein S5e (rpS5e, "e" stands for "eukaryotic") and eIFs
      within the mammalian PIC, assembled on either model canonical or IRES-containing
      mRNA. Using immunoblotting and mass spectrometry, we show that with both types of
      mRNA, rpS5e crosslinks to eIF2alpha. Comparative analysis of peptides resulting
      from trypsinolysis of the crosslinked proteins before and after crosslink
      reversal reveals crosslinked peptides in the N-terminal parts of rpS5e and
      eIF2alpha. Application of these data to a model PIC structure obtained with the
      use of available structures indicates that eIF2alpha undergoes major conformation
      rearrangements to enable contacts of the factor with rpS5e. These contacts are
      suggested to maintain the correct positioning of eIF2alpha relative to other PIC
      components; this could be essential for start-codon selection by the PIC. 

PMID- 24106101
TI  - From a gene-centric to whole-proteome view of differentiation of T helper cell
      subsets.
AB  - Proper differentiation of naive T helper cells into functionally distinct subsets
      is of critical importance to human health. Consequently, the process is tightly
      controlled by a complex intracellular signalling network. To dissect the
      regulatory principles of this network, immunologists have early on embraced
      system-wide transcriptomics tools, leading to identification of large panels of
      potential regulatory factors. In contrast, the use of proteomics approaches in T
      helper cell research has been notably rare, and to this date relatively few high
      throughput datasets have been reported. Here, we discuss the importance of such
      research and envision the possibilities afforded by mass spectrometry-based
      proteomics in the near future. 

PMID- 24106103
TI  - Visual servoing in medical robotics: a survey. Part I: endoscopic and direct
      vision imaging - techniques and applications.
AB  - BACKGROUND: Intra-operative imaging is widely used to provide visual feedback to
      a clinician when he/she performs a procedure. In visual servoing, surgical
      instruments and parts of tissue/body are tracked by processing the acquired
      images. This information is then used within a control loop to manoeuvre a
      robotic manipulator during a procedure. METHODS: A comprehensive search of
      electronic databases was completed for the period 2000-2013 to provide a survey
      of the visual servoing applications in medical robotics. The focus is on medical
      applications where image-based tracking is used for closed-loop control of a
      robotic system. RESULTS: Detailed classification and comparative study of various
      contributions in visual servoing using endoscopic or direct visual images are
      presented and summarized in tables and diagrams. CONCLUSION: The main challenges
      in using visual servoing for medical robotic applications are identified and
      potential future directions are suggested. 'Supervised automation of medical
      robotics' is found to be a major trend in this field.

PMID- 24106104
TI  - Functional dissection of protein domains involved in the immunomodulatory
      properties of PE_PGRS33 of Mycobacterium tuberculosis.
AB  - PE_PGRSs are a large family of proteins identified in Mycobacterium tuberculosis
      complex and in few other pathogenic mycobacteria. The PE domain of PE_PGRS33
      mediates localization of the protein on the mycobacterial cell surface, where the
      PGRS domain is available to interact with host components. In this study,
      PE_PGRS33 and its functional deletion mutants were expressed in M. smegmatis, and
      in vitro and in vivo assays were used to dissect the protein domains involved in
      the immunomodulatory properties of the protein. We demonstrate that PE_PGRS33
      mediated secretion of TNF-alpha by macrophages occurs by extracellular
      interaction with TLR2. Our results also show that while the PGRS domain of the
      protein is required for triggering TNF-alpha secretion, mutation in the PE domain
      affects the pro-inflammatory properties of the protein. These results indicate
      that PE_PGRS33 is a protein with immunomodulatory activity and that protein
      stability and localization on the mycobacterial surface can affect these
      properties. 

PMID- 24106105
TI  - HA-coated chitosan nanoparticles for CD44-mediated nucleic acid delivery.
AB  - CD44, the main receptor of hyaluronic acid (HA), is overexpressed in several
      pathological conditions and therefore can be seen as an interesting target for
      therapeutic intervention. Here, an approach using HA-coated chitosan (CS)
      triphosphate (TPP) nanoparticles is investigated, using CS with different
      molecular weight (25 and 684 kDa), which influences HA presentation, and
      enzymatic and pH stability. In a study of nuclease stability, post-digestion of
      nanoparticles with chitosanase reveals that pDNA is at least partially degraded
      by DNAse; this may suggest that literature results overestimate the polyplex
      stability against nucleases. Using cells with a significantly different CD44
      expression (RAW 264.7 macrophages-high levels; K562 leukemia cells-low levels;
      Kelly neuroblastoma cells-absent), the selectivity of CD44-mediated transfection
      is proven. Further, using luciferase pDNA and then later anti-luc siRNA, low MW
      CS-based nanoparticles show the best results despite a lower internalization
      efficiency; this effect is ascribed to a more efficient endosomal disruption and
      nucleic acid de-complexation. 

PMID- 24106106
TI  - Amythiamicin D and related thiopeptides as inhibitors of the bacterial elongation
      factor EF-Tu: modification of the amino acid at carbon atom C2 of ring C
      dramatically influences activity.
AB  - Three analogues of amythiamicin D, which differ in the substitution pattern at
      the methine group adjacent to C2 of the thiazole ring C, were prepared by de novo
      total synthesis. In amythiamicin D, this carbon atom is (S)-isopropyl
      substituted. Two of the new analogues carry a hydroxymethyl in place of the
      isopropyl group, one at an S- (compound 3 a) and the other at an R-configured
      stereogenic center (3 b). The third analogue, 3 c, contains a benzyloxymethyl
      group at an S-configured stereogenic center. Compounds 3 b and 3 c showed no
      inhibitory effect toward various bacterial strains, nor did they influence the
      translation of firefly luciferase. In stark contrast, compound 3 a inhibited the
      growth of Gram-positive bacteria Staphylococcus aureus (strains NCTC and Mu50)
      and Listeria monocytogenes EGD. In the firefly luciferase assay it proved more
      potent than amythiamicin D, and rescue experiments provided evidence that
      translation inhibition is due to binding to the bacterial elongation factor Tu
      (EF-Tu). The results were rationalized by structural investigations and by
      molecular dynamics simulations of the free compounds in solution and bound to the
      EF-Tu binding site. The low affinity of compound 3 b was attributed to the
      absence of a critical hydrogen bond, which stabilizes the conformation required
      for binding to EF-Tu. Compound 3 c was shown not to comply with the binding
      properties of the binding site. 

PMID- 24106107
TI  - Gross anatomy videos: student satisfaction, usage, and effect on student
      performance in a condensed curriculum.
AB  - Anatomy educators are being tasked with delivering the same quantity and quality
      of material in the face of fewer classroom and laboratory hours. As a result they
      have turned to computer-aided instruction (CAI) to supplement and augment
      curriculum delivery. Research on the satisfaction and use of anatomy videos, a
      form of CAI, on examination performance continues to grow. The purpose of this
      study was to describe the usage and effect on examination scores of a series of
      locally produced anatomy videos after an 11% curriculum reduction. First-year
      medical students (n = 40) were given access to the videos and the prior year's
      students (n = 40) were used as historical controls. There was no significant
      difference in demographics between the two groups. The survey response rate was
      85% (n = 34) in the experimental group. The students found the videos to be
      highly satisfying (median = 5 on a five-point Likert scale, interquartile range =
      1) and used them on average 1.55 times/week (SD +/- 0.77). Availability of the
      videos did have a statistically significant effect (4% improvement) on the final
      laboratory examination (p = 0.039). This suggests that the videos were a well
      received form of CAI that may be useful in bridging the gap created by a
      reduction in gross anatomy course contact hours.

PMID- 24106108
TI  - Injectable biphasic calcium phosphate cements as a potential bone substitute.
AB  - Apatitic calcium phosphate cements (CPCs) have been widely used as bone grafts
      due to their excellent osteoconductive properties, but the degradation properties
      are insufficient to stimulate bone healing in large bone defects. A novel
      approach to overcome the lack of degradability of apatitic CPC involves the
      development of biphasic CPCs (BCPC) based on tricalcium phosphate (TCP) in both
      alpha- and beta-polymorphs. The aim of the current study was to prepare and
      analyze the physicochemical properties of BCPCs based on dual phase alpha/beta
      TCP as obtained by heat treatment of pure alpha-TCP. The handling and mechanical
      characteristics of the samples as well as the degradation behavior under in vitro
      condition were investigated and compared with a standard monophasic alpha-TCP
      based CPC. The results showed that different heat treatments of commercially
      available alpha-TCP allowed the formation of biphasic calcium phosphate powder
      with a variety of alpha/beta-TCP ratios. The use of biphasic powder particles as
      a reactant for CPCs resulted into increased setting and injectability times of
      the final BCPCs. During hardening of the cements, the amount of apatite formation
      decreased with increasing beta-TCP content in the biphasic precursor powders. The
      morphology of the monophasic CPC consisted of plate-like crystals, whereas needle
      like crystals were observed for BCPCs. In vitro degradation tests demonstrated
      that dissolution rate and corresponding calcium release from the set cements
      increased considerably with increasing beta-TCP content, suggesting that apatitic
      CPCs can be rendered degradable by using biphasic alpha/beta-TCP as powder
      precursor phase.

PMID- 24106109
TI  - A dual-responsive mesoporous silica nanoparticle for tumor-triggered targeting
      drug delivery.
AB  - A novel pH- and redox- dual-responsive tumor-triggered targeting mesoporous
      silica nanoparticle (TTTMSN) is designed as a drug carrier. The peptide RGDFFFFC
      is anchored on the surface of mesoporous silica nanoparticles via disulfide
      bonds, which are redox-responsive, as a gatekeeper as well as a tumor-targeting
      ligand. PEGylated technology is employed to protect the anchored peptide ligands.
      The peptide and monomethoxypolyethylene glycol (MPEG) with benzoic-imine bond,
      which is pH-sensitive, are then connected via "click" chemistry to obtain TTTMSN.
      In vitro cell research demonstrates that the targeting property of TTTMSN is
      switched off in normal tissues with neutral pH condition, and switched on in
      tumor tissues with acidic pH condition after removing the MPEG segment by
      hydrolysis of benzoic-imine bond under acidic conditions. After deshielding of
      the MPEG segment, the drug-loaded nanoparticles are easily taken up by tumor
      cells due to the exposed peptide targeting ligand, and subsequently the redox
      signal glutathione in tumor cells induces rapid drug release intracellularly
      after the cleavage of disulfide bond. This novel intelligent TTTMSN drug delivery
      system has great potential for cancer therapy. 

PMID- 24106110
TI  - Imatinib cessation in children and adolescents with chronic myeloid leukemia in
      chronic phase.
AB  - Imatinib can be safely discontinued in adults with chronic myeloid leukemia (CML)
      where there is a prolonged complete molecular response (CMR). No data are
      available in the pediatric population. Six children with CML discontinued
      imatinib by themselves. Only three of them were in CMR but for <2 years. A
      significant increase in transcript level was observed in all six patients after
      cessation of imatinib and five patients lost the major molecular response (MMR).
      Four patients regained the MMR within 3 months. Cessation of imatinib in children
      is not recommended outside a trial, particularly in patients without prolonged
      CMR.

PMID- 24106111
TI  - Comparative analysis of aqueous humor cytokine levels between patients with
      exudative age-related macular degeneration and normal controls.
AB  - PURPOSE: To investigate the cytokine markers associated with exudative AMD
      present in aqueous humor. This goal was achieved by comparing the concentrations
      of more than 500 molecules in aqueous humor, between exudative AMD patients and
      controls. METHODS: Aqueous humor samples were acquired from 20 patients with
      exudative AMD and 20 control subjects. Raybio human antibody array technology was
      used to simultaneously screen for any difference in the expression of any of 507
      molecules. To validate the antibody array result, concentrations of insulin-like
      growth factor binding protein 2 (IGFBP-2), insulin-like growth factor-1 (IGF-1),
      and VEGF were measured by ELISA. RESULTS: Twenty molecules studied exhibited
      intergroup differences. Twelve molecules including IGFBP-2, IGFBP-6, IGFBP-7, and
      glucocorticoid-induced tumor necrosis factor receptor family related gene (GITR)
      ligand, were detected in high densities in exudative AMD patients. Eight other
      molecules were present at higher concentrations in control patients. ELISA
      confirmed that IGFBP-2 levels were higher in patients with exudative AMD (7.47 +/
      6.19 ng/mL) in comparison with control subjects (3.07 +/- 3.34 ng/mL, P =
      0.008). IGF-1 and VEGF levels were also increased in the former group (2.20 +/-
      0.26 vs. 1.99 +/- 0.35 ng/mL, P = 0.040; 122.25 +/- 63.24 vs. 86.98 +/- 44.41
      pg/mL, P = 0.048, respectively). CONCLUSIONS: The pattern of cytokine expression
      in the aqueous humor of exudative AMD patients varies from that of normal control
      subjects. The increased levels of IGFBP-2 and IGF-1 in exudative AMD eyes
      indicate that the altered expression of IGF-related molecules may be involved in
      disease pathogenesis and suggests potential biomarkers for exudative AMD.

PMID- 24106112
TI  - Endogenous IgG affects the cell biology of RPE cells and involves the TLR4
      pathway.
AB  - PURPOSE: RPE is a key component of the blood-ocular barrier (BOB) and is equipped
      with immunological molecules such as toll-like receptors (TLRs) and complement
      receptors, which together orchestrate the innate and adaptive immunity of the
      eye. Immunoglobulin G (IgG) in the aqueous humor and vitreous body has
      traditionally been thought to be derived from serum via transcytosis across the
      BOB. Our previous work validated production of endogenous IgG by RPE cells
      locally. However, the function and role of this IgG in the intraocular immunity
      is poorly understood. METHODS: After confirming IgG production in a human RPE
      cell line (ARPE-19) with immunofluorescence, in situ hybridization, and RT-PCR,
      we further investigated the function of endogenous IgG in RPE biology with MTS,
      flow cytometry, and cell invasion analysis after downregulation of IgG by siRNA.
      Involvement of the TLR4 pathway was also studied using Western blot, ELISA and
      confocal microscopy. RESULTS: Endogenous IgG is crucial for support of
      proliferation, mitosis, migration, and inhibition of apoptosis of RPE. Moreover,
      production of endogenous IgG by RPE is regulated by the TLR4 pathway in a
      concentration- and duration-dependent manner, and IgG affects the activation of
      the TLR4 pathway in a synergistic manner. Activation of the FcgammaR I pathway
      and production of IL-10 could be induced by IgG derived from RPE. CONCLUSIONS:
      These data suggest that endogenous IgG may be a molecule that is essential for
      the physiological function of RPE, and suggest IgG is important for regulating
      intraocular immune responses under physiologic and pathologic conditions.

PMID- 24106113
TI  - Serum ferritin and hemoglobin are independently associated with wider retinal
      venular caliber: the Tromso Study 2001-2008.
AB  - PURPOSE: To investigate if markers of iron body stores and hemoglobin are
      associated with retinal vascular caliber. METHODS: This was a population-based
      study including 2993 participants of the fifth and sixth surveys of the Tromso
      Study in Norway, conducted in 2001-2002 and 2007-2008. The association between
      levels of s-ferritin, transferrin saturation, and hemoglobin in the fifth survey
      and retinal vascular caliber in the sixth survey was assessed by multivariable
      linear regression models. RESULTS: Men had higher levels of hemoglobin and s
      ferritin than women. Hemoglobin was associated with wider retinal venules in both
      men and women (mean difference between highest compared to lowest sex-specific
      quartile: men 5.99 MUm, P = 0.001; women 7.28 MUm, P < 0.001). S-ferritin was
      associated with wider retinal venules in men but not women, independent of
      traditional risk factors (mean difference between highest compared to lowest sex
      specific quartile: men 4.21 MUm, P = 0.013; women -0.21 MUm, P = 0.89). The
      association in men was attenuated, but still significant, with adjustment for
      hemoglobin. S-ferritin and level of hemoglobin were not associated with
      arteriolar caliber in either sex. Transferrin saturation was not associated with
      retinal vascular caliber. CONCLUSIONS: Level of hemoglobin was associated with
      wider retinal venules in both sexes while s-ferritin was associated with wider
      retinal venular caliber only in men. Men have higher levels of stored iron, and
      this may underlie the observed sex difference in the association between s
      ferritin and retinal vascular caliber.

PMID- 24106114
TI  - Macular choroidal thickness and volume in healthy pediatric individuals measured
      by swept-source optical coherence tomography.
AB  - PURPOSE: We evaluated the choroidal thickness and volume in healthy pediatric
      individuals by swept-source optical coherence tomography (SS-OCT) and compared
      the findings to those of adults. METHODS: We examined 100 eyes of 100 healthy
      pediatric volunteers (3-15 years) and 83 eyes of 83 healthy adult volunteers (24
      87 years) by SS-OCT with a tunable long wavelength laser source. The three
      dimensional raster scan protocol was used to construct a choroidal thickness map.
      When the built-in software delineated an erroneous chorioscleral border in the B
      scan images, manual segmentation was used. RESULTS: The central choroidal
      thickness and volume within a 1.0-mm circle were significantly larger in the
      children (260.4 +/- 57.2 MUm, 0.205 +/- 0.045 mm(3)) than in the adults (206.1 +/
      72.5 MUm, 0.160 +/- 0.056 mm(3), both P < 0.0001). In the children, the mean
      choroidal thickness of the nasal area was significantly thinner than that of all
      other areas (P < 0.005). Pediatric choroidal thinning with increasing age in the
      central area was faster than that in the outer areas. Stepwise regression
      analysis showed that the axial length and body mass index had the highest
      correlation with the choroidal thickness (R(2) = 0.313, P < 0.0001). CONCLUSIONS:
      The macular choroidal thickness and volume in the pediatric individuals were
      significantly larger than those in the adults. The pediatric choroidal thinning
      with increasing age is more rapid in the central area. Pediatric choroidal
      thickness is associated with several systemic or ocular parameters, especially
      the axial length and body mass index. These differences should be remembered when
      the choroidal thickness is evaluated in pediatric patients with retinochoroidal
      diseases.

PMID- 24106115
TI  - Correlation between foveal cone outer segment tips line and visual recovery after
      epiretinal membrane surgery.
AB  - PURPOSE: To determine whether there is a significant correlation between the
      integrity of the foveal microstructures and the best-corrected visual acuity
      (BCVA) after pars plana vitrectomy for epiretinal membrane (ERM) removal.
      METHODS: This was a retrospective, interventional case series. Forty-six eyes of
      45 patients with an ERM underwent vitrectomy. The foveal area was examined by
      spectral-domain-optical coherence tomography (SD-OCT) preoperatively and
      postoperatively. The correlation between the length of the photoreceptor cone
      outer segment tips (COST) line defect, the inner segment/outer segment junction
      (IS/OS) line defect, the external limiting membrane (ELM) line defect, and the
      BCVA was determined. RESULTS: The length of the COST line defect was
      significantly correlated with the BCVA at postoperative 1, 3, 6, 9, and 12 months
      (P < 0.001 for all). Forward stepwise regression analyses showed that the
      postoperative BCVA was significantly correlated with the length of COST line
      defect (P < 0.001) but not with the IS/OS line and ELM line defects for up to 6
      months. The preoperative length of the COST line defect was significantly
      correlated with the postoperative BCVA at 12 months (P = 0.005), but the lengths
      of the IS/OS line defect and ELM line defect were not. The factor that best
      predicted the postoperative BCVA was the length of the preoperative COST line
      defect (P = 0.04) but not the preoperative BCVA (P = 0.69). CONCLUSIONS: The
      recovery of the foveal COST line defect is correlated with the BCVA after ERM
      surgery. The length of the preoperative COST line defect can predict the
      potential foveal function. (ClinicalTrials.gov number, NCT01549249.).

PMID- 24106116
TI  - Development of genetically modified eliminable human dermal fibroblast feeder
      cells for ocular surface regeneration medicine.
AB  - PURPOSE: Cultured human corneal limbal stem/progenitor cells are usually
      established and maintained on feeder layers. However, animal feeder cells are
      associated with viral infection, pathogen transmission, and xenogenic
      contamination. All feeder cells also can be mixed easily into cell-sheet
      production, causing self-contamination. We developed a line of labeled,
      immortalized, eliminable human dermal fibroblast cells to eliminate these
      problems. METHODS: The enhanced green fluorescent protein gene, human-derived
      telomerase reverse transcriptase gene, and herpes simplex virus thymidine kinase
      gene were transfected into human dermal fibroblast cells to establish labeled,
      immortalized, eliminable feeder cells. Established eliminable dermal fibroblasts
      (TERT+TK-D) were treated with mitomycin, cocultured with human limbal
      stem/progenitor cells to regenerate epithelium sheets, and compared with 3T3
      feeder cells. RESULTS: Established TERT+TK-D feeder cells maintained
      immortalization, visualization, and eliminable characteristics during 6 months of
      continuous passages. The colony-forming efficiency of limbal stem/progenitor
      cells was similar in the TERT+TK-D group (11.77 +/- 0.21%) and the 3T3 group
      (12.8 +/- 1.61%) (P = 0.332). All cell sheets were well stratified into 4 to 5
      layers. The TERT+TK-D group colonies and epithelial cell sheets showed weaker
      staining of corneal epithelium differentiation marker K3 than the 3T3 group and
      quantitative analysis of mRNA transcripts. Moreover, PCR analysis against the
      long terminal repeat sequence of the lentiviral vector integrated into the
      genetically modified feeder cells showed no contamination of ganciclovir-treated
      regeneration epithelial sheets. CONCLUSIONS: Genetically modified, labeled,
      immortalized, eliminable human dermal feeder cells are promising substitutes for
      3T3 feeder cells for xenogeny-free ocular surface regeneration.

PMID- 24106117
TI  - Relationship between retinal layer thickness and focal macular electroretinogram
      components after epiretinal membrane surgery.
AB  - PURPOSE: To study the effect of epiretinal membrane (ERM) removal on the function
      and structure of the retina, and to determine whether the functional changes were
      correlated with the changes in the thickness of different retinal layers.
      METHODS: Focal macular electroretinography (FMERG) and spectral-domain optical
      coherence tomography (SD-OCT) were performed on 17 eyes of 15 patients before and
      after ERM surgery. The parafoveal retina was divided into an inner layer, a
      middle layer, and an outer layer in the OCT images. The thickness of each layer
      was measured before and after the ERM surgery. The a-wave, b-wave, and
      oscillatory potentials (OPs) of the FMERGs were analyzed before and after the ERM
      surgery. RESULTS: The thickness of the inner and middle retinal layers was
      significantly reduced after surgery (by 39% and 23%, respectively). The mean
      amplitudes of the b-waves and OPs at 6 months postoperatively were significantly
      larger than those recorded preoperatively (by 21% and 61%, respectively). The
      ratios of the pre- to postoperative b-wave and OP amplitudes were correlated with
      the thickness reduction of the middle retinal layer (b-wave, r = -0.51, P < 0.05;
      OPs, r = -0.82, P < 0.01). CONCLUSIONS: The significant correlations between the
      reduction in the thickness of the middle retinal layer and increase in the
      amplitude of the b-waves and OPs suggest that the improvement of macular function
      after ERM peeling is due to the decrease in the thickness of the middle retinal
      layer.

PMID- 24106118
TI  - Sustained neuroprotection from a single intravitreal injection of PGJ2 in a
      rodent model of anterior ischemic optic neuropathy.
AB  - PURPOSE: Nonarteritic anterior ischemic optic neuropathy (NAION) is the most
      common cause of sudden optic nerve-related vision loss in persons older than 50
      in the United States. There currently is no treatment for this disorder. We
      previously showed that systemic administration of 15-deoxy, delta (12, 14)
      prostaglandin J2 (PGJ2) is neuroprotective in our rodent model of AION (rAION).
      In this study, we determined if a single intravitreal (IVT) injection of PGJ2 is
      neuroprotective after rAION, and if this method of administration is toxic to the
      retina, optic nerve, or both. METHODS: TOXICITY was assessed after a single IVT
      injection of PGJ2 in one eye and PBS in the contralateral eye of normal, adult
      Long-Evans rats. EFFICACY was assessed by inducing rAION in one eye and injecting
      either PGJ2 or vehicle immediately following induction, with the fellow eye
      serving as naive control. Visual evoked potentials (VEPs) and ERGs were performed
      before induction and at specific intervals thereafter. Animals were euthanized 30
      days after induction, after which immunohistochemistry, transmission electron
      microscopy, and quantitative stereology of retinal ganglion cell (RGC) numbers
      were performed. RESULTS:  TOXICITY: IVT PGJ2 did not alter the VEP or ERG
      compared with PBS-injected control eyes, and neither IVT PGJ2 nor PBS reduced
      overall RGC numbers. EFFICACY: IVT PGJ2 preserved VEP amplitude, reduced optic
      nerve edema, and resulted in significant preservation of RGCs and axons in eyes
      with rAION. CONCLUSIONS: A single IVT injection of PGJ2 is nontoxic to the retina
      and optic nerve and neuroprotective when given immediately after rAION induction.

PMID- 24106119
TI  - A new human primary epithelial cell culture model to study conjunctival
      inflammation.
AB  - PURPOSE: To develop a complete and optimized method to expand in culture human
      conjunctival epithelial cells from cadaveric donor samples. METHODS: Epithelial
      cells were obtained from cadaveric conjunctival tissue (n = 47). Preplating and
      differential trypsinization were optimized to eliminate stromal contamination.
      Epithelial cells were grown with five different media: control, epithelial growth
      factor (EGF)-enriched, H2O2-supplemented, fibroblast-conditioned, and human serum
      media. Adhesion, proliferation, colony forming efficiency (CFE), and percentage
      of CK19(+) and Ki67(+) cells were determined with the five different media. Cells
      were characterized by immunofluorescence and/or Western blotting techniques for
      the expression of CK4, CK7, CK19, MUC5AC, vimentin, FSP-1, Ki67, E-cadherin, and
      zonula occludens (ZO)-1 markers. In addition, cells were treated with TNF-alpha
      and levels of secreted IL-6 were measured by enzyme-linked immunosorbent assay.
      RESULTS: Pure epithelial cell cultures were obtained. Human serum medium showed
      the best properties in proliferation and CFE, while maintaining epithelial
      phenotype. Cells with this medium were passaged up to five times, although they
      maintained all epithelial characteristics only through passage 3. Cultured cells
      expressed epithelial markers, but not stromal ones. The number of MUC5AC(+) cells
      increased throughout the passages, whereas Ki67(+) cell numbers decreased. Cells
      in culture maintained adherens and tight junctions, and responded to TNF-alpha
      treatment by releasing more IL-6, showing that they can be used for inflammation
      assays. CONCLUSIONS: We have developed a complete protocol to expand conjunctival
      epithelial cells from cadaveric tissue. This culture system responded to an
      inflammatory stimulus, so it could be used to develop a more complex in vitro
      model of inflammation.

PMID- 24106120
TI  - Involvement of cyclin D and p27 in cell proliferation mediated by ROCK inhibitors
      Y-27632 and Y-39983 during corneal endothelium wound healing.
AB  - PURPOSE: To investigate the molecular mechanism of Rho-associated kinase (ROCK)
      inhibitors Y-27632 and Y-39983 on corneal endothelial cell (CEC) proliferation
      and their wound-healing effect. METHODS: The expression of G1 proteins of the
      cell cycle and expression of phosphorylated Akt in monkey CECs (MCECs) treated
      with Y-27632 were determined by Western blotting. The effect of Y-39983 on the
      proliferation of MCECs and human CECs (HCECs) was evaluated by both Ki67 staining
      and incorporation of BrdU. As an in vivo study, Y-39983 was topically instilled
      in a corneal-endothelial partially injured rabbit model, and CEC proliferation
      was then evaluated. RESULTS: Investigation of the molecular mechanism of Y-27632
      on CEC proliferation revealed that Y-27632 facilitated degradation of p27Kip1
      (p27), and promoted the expression of cyclin D. When CECs were stimulated with Y
      27632, a 1.7-fold increase in the activation of Akt was seen in comparison to the
      control after 1 hour. The presence of LY294002, the PI 3-kinase inhibitor,
      sustained the level of p27. When the efficacy of Y-39983 on cell proliferation
      was measured in a rabbit model, Y-39983 eye-drop instillation demonstrated rapid
      wound healing in a concentration range of 0.095 to 0.95 mM, whereas Y-27632
      demonstrated rapid wound healing in a concentration range of 3 to 10 mM.
      CONCLUSIONS: These findings show that ROCK inhibitors employ both cyclin D and
      p27 via PI 3-kinase signaling to promote CEC proliferation, and that Y-39983 may
      be a more potent agent than Y-27632 for facilitating corneal endothelium wound
      healing.

PMID- 24106121
TI  - Aurintricarboxylic acid inhibits complement activation, membrane attack complex,
      and choroidal neovascularization in a model of macular degeneration.
AB  - PURPOSE: Immunocytochemical and genetic data implicate a significant role for the
      activation of complement in the pathology of AMD. Individuals homozygous for a
      Y402H polymorphism in Factor H have elevated levels of membrane attack complex
      (MAC) in their choroidal blood vessels and RPE relative to individuals homozygous
      for the wild-type allele. An R95X polymorphism in C9, a protein necessary for the
      final assembly of MAC, is partially protective against the formation of choroidal
      neovascularization (CNV) in AMD patients. Aurintricarboxylic Acid (ATA) is a
      small molecule inhibitor of MAC. Our hypothesis was that attenuation of the
      formation of MAC on ocular tissues by ATA may protect mice against laser-induced
      CNV. METHODS: The ability of ATA to inhibit human complement-mediated cell lysis,
      inhibit formation of human MAC, and inhibit formation of tubes by endothelial
      cells was examined in vitro. Subsequently, the Bruch's membrane of adult mice was
      damaged using an argon laser, followed by intravitreal injection of ATA. One week
      later, choroidal flat mounts from these mice were stained for the presence of
      MAC, endothelial cells, and macrophages. RESULTS: ATA protects cells from human
      complement-mediated lysis, attenuates assembly of the MAC, and inhibits tube
      formation by endothelial cells in vitro. ATA also attenuates CNV, MAC deposition,
      and macrophage infiltration in a murine model of exudative AMD. CONCLUSIONS: ATA
      warrants further study as a potential drug for the treatment of exudative and
      nonexudative AMD.

PMID- 24106122
TI  - Involvement of Nox2 NADPH oxidase in retinal neovascularization.
AB  - PURPOSE: The proliferation of new blood vessels in the retina is a leading cause
      of vision impairment. Nicotinamide adenine dinucleotide phosphate (NADPH) oxidase
      (Nox) is involved in cell signaling for ischemia-induced angiogenesis, but its
      role in retinal neovascularization is unclear. We have analyzed the dependence of
      retinal neovascularization on the Nox2 isoform in oxygen-induced retinopathy
      (OIR) in mice. METHODS: Neonatal C57BL/6 mice aged 7 days (P7) were placed in a
      hyperoxic chamber (75% O2) for 5 days, followed by 5 days of exposure to room
      air. Eyes were harvested on P8 and P17 for the quantification of retinal vaso
      obliteration and neovascularization, respectively. The retinal expression of Nox2
      and VEGF-A were measured by RT-PCR, while superoxide generation was detected by
      in situ dihydroethidium (DHE) staining of fresh frozen sections. RESULTS: In wild
      type (WT) mice, OIR was characterized by central retinal vaso-obliteration at P8
      and neovascularization at P17, which was associated with increases in Nox2 and
      VEGF-A gene expression, superoxide generation, and accumulation of Iba-1 positive
      cells in the inner retina. In contrast, Nox2 knockout mice exhibited markedly
      less retinal neovascularization and VEGF-A mRNA expression at P17, despite
      showing comparable vaso-obliteration at P8. These changes were accompanied by
      reductions in DHE fluorescence and Iba-1-positive cell accumulation in the
      hypoxic retina. CONCLUSIONS: The Nox2-generated reactive oxygen species (ROS)
      facilitate the retinal expression of VEGF-A and neovascularization in this mouse
      model of OIR. Therapies targeting Nox2 could be of value to reduce aberrant
      retinal neovascularization in retinopathy of prematurity, diabetes, and other
      disease processes driven by VEGF.

PMID- 24106124
TI  - Rapamycin inhibits the production of myofibroblasts and reduces corneal scarring
      after photorefractive keratectomy.
AB  - PURPOSE: Corneal stromal scarring partly involves the production of corneal
      myofibroblasts. The purpose of this study was to examine the effects of rapamycin
      (an inhibitor of the mammalian target of rapamycin [mTOR] pathway) on
      myofibroblast formation in vitro and in-vivo. METHODS: Human corneal fibroblasts
      were grown in culture and transformed into myofibroblasts using TGF-beta (2
      ng/mL). The phosphorylation (activation) of the mTOR pathway was examined by
      immunoblotting. Cell proliferation with and without rapamycin was examined by
      thiazolyl blue tetrazolium bromide (MTT) assay and Ki67 staining. The expression
      of the myofibroblast differentiation marker smooth muscle actin (SMA) was
      examined by immunostaining and immunoblotting. The functional effects of
      rapamycin were measured using a gel contraction assay. For in vivo studies, 140
      MUm laser ablation was performed on rabbit corneas followed by subconjunctival
      rapamycin or vehicle. Corneal haze development was graded at 4 weeks, while the
      expression of myofibroblast markers was examined by immunostaining and
      immunoblotting. RESULTS: The TGF-beta activated the mTOR pathway with peak
      phosphorylation at 2 to 4 hours. Treatment of corneal fibroblasts with rapamycin
      reduced their proliferation by 46% compared to control. Rapamycin significantly
      inhibited TGF-beta-induced expression of myofibroblast markers (17.2% SMA
      positive cells with rapamycin compared to 69.0% in control). Rapamycin also
      significantly inhibited TGF-beta-induced collagen gel contraction. In the rabbit
      eyes treated with rapamycin, corneal haze development was significantly less
      compared to controls (0.75 +/- 0.4 vs. 2.17 +/- 0.7). CONCLUSIONS: Rapamycin
      appears to inhibit proliferation and differentiation of corneal myofibroblasts
      and, thus, may provide an effective therapeutic measure for preventing corneal
      scarring.

PMID- 24106123
TI  - Myosin 6 is required for iris development and normal function of the outer
      retina.
AB  - PURPOSE: To determine the molecular basis and the pathologic consequences of a
      chemically induced mutation in the translational vision research models 89
      (tvrm89) mouse model with ERG defects. METHODS: Mice from a G3 N-ethyl-N
      nitrosourea mutagenesis program were screened for behavioral abnormalities and
      defects in retinal function by ERGs. The chromosomal position for the recessive
      tvrm89 mutation was determined in a genome-wide linkage analysis. The critical
      region was refined, and candidate genes were screened by direct sequencing. The
      tvrm89 phenotype was characterized by circling behavior, in vivo ocular imaging,
      detailed ERG-based studies of the retina and RPE, and histological analysis of
      these structures. RESULTS: The tvrm89 mutation was localized to a region on
      chromosome 9 containing Myo6. Sequencing identified a T->C point mutation in the
      codon for amino acid 480 in Myo6 that converts a leucine to a proline. This
      mutation does not confer a loss of protein expression levels; however, mice
      homozygous for the Myo6(tvrm89) mutation display an abnormal iris shape and
      attenuation of both strobe-flash ERGs and direct-current ERGs by 4 age weeks,
      neither of which is associated with photoreceptor loss. CONCLUSIONS: The tvrm89
      phenotype mimics that reported for Myosin6-null mice, suggesting that the
      mutation confers a loss of myosin 6 protein function. The observation that
      homozygous Myo6(tvrm89) mice display reduced ERG a-wave and b-wave components, as
      well as components of the ERG attributed to RPE function, indicates that myosin 6
      is necessary for the generation of proper responses of the outer retina to light.

PMID- 24106125
TI  - A synthetic lymph node containing inactivated Treponema pallidum cells elicits
      strong, antigen-specific humoral and cellular immune responses in mice.
AB  - The goal of this study was to investigate the use of a synthetic lymph node (SLN)
      for delivery of Treponema pallidum (Tp) antigens. Immune responses of C57BL/6
      mice were analyzed at 4, 8, and 12 weeks after SLN implantation. Group 1 mice
      received SLN with no antigen; Group 2, SLN with formalin-inactivated Tp (f-Tp);
      and Group 3, SLN with f-Tp plus a CpG oligodeoxynucleotide. When tested by ELISA,
      sera from Group 2 and Group 3 mice showed stronger IgG antibody reactivity than
      sera from Group 1 mice to sonicates of f-Tp or untreated Tp, but not to sonicate
      of normal rabbit testicular extract at all times. The IgG1 level was higher than
      IgG2c level for Group 2 mice at all times and for Group 3 mice at 4 and 8 weeks.
      IgG1 and IgG2c levels were nearly equivalent for Group 3 mice at 12 weeks.
      Immunoblotting showed that IgG from Group 2 and Group 3 mice recognized several
      Tp proteins at all times. Supernatants of splenocytes from Group 2 and Group 3
      mice contained significantly more IFNgamma than those from Group 1 mice after
      stimulation with f-Tp at all times. A significant level of IL-4 was not detected
      in any supernatants. These data show that strong humoral and cellular immune
      responses to Tp can be elicited via a SLN.

PMID- 24106126
TI  - Purification and analysis of mono-PEGylated HSA by hydrophobic interaction
      membrane chromatography.
AB  - We discuss the purification of mono-PEGylated HSA by hydrophobic interaction
      membrane chromatography. The hydrophobicity difference between the different
      fractionated species was induced by the addition of a lyotropic salt that caused
      phase transition of PEG (hydrophilic under normal condition) to a mildly
      hydrophobic form. The HSA PEGylation reaction mixture was mixed with lyotropic
      salt and passed through a stack of hydrophilized polyvinylidene fluoride membrane
      discs. Unmodified HSA was obtained in the flow through, while the PEGylated forms
      of the protein bound to the membrane and could be eluted by reducing the salt
      concentration. Among the three major PEGylated forms of HSA present in the feed
      (i.e. mono-, di-, and tri-), mono-PEGylated HSA was eluted first and could be
      resolved from the others. The purified material was analyzed by SDS-PAGE, dynamic
      light scattering, and SEC combined with multi-angle light scattering. All these
      analytical techniques indicated the presence of species that has a molar mass
      consistent with mono-PEGylated HSA. A scaled-down version of the membrane
      chromatographic methods could be used for the rapid and sensitive analysis of
      PEGylated proteins. 

PMID- 24106127
TI  - Surgical value of contrast-enhanced ultrasonography in laparoscopic hepatectomy
      using energy devices.

PMID- 24106128
TI  - Hydrogen-bonded complexes and blends of poly(acrylic acid) and methylcellulose:
      nanoparticles and mucoadhesive films for ocular delivery of riboflavin.
AB  - Poly(acrylic acid) (PAA) and methylcellulose (MC) are able to form hydrogen
      bonded interpolymer complexes (IPCs) in aqueous solutions. In this study, the
      complexation between PAA and MC is explored in dilute aqueous solutions under
      acidic conditions. The formation of stable nanoparticles is established, whose
      size and colloidal stability are greatly dependent on solution pH and polymers
      ratio in the mixture. Poly(acrylic acid) and methylcellulose are also used to
      prepare polymeric films by casting from aqueous solutions. It is established that
      uniform films can be prepared by casting from polymer mixture solutions at pH 3.4
      4.5. At lower pHs (pH < 3.0) the films have inhomogeneous morphology resulting
      from strong interpolymer complexation and precipitation of polycomplexes, whereas
      at higher pHs (pH 8.3) the polymers form fully immiscible blends because of the
      lack of interpolymer hydrogen-bonding. The PAA/MC films cast at pH 4 are shown to
      be non-irritant to mucosal surfaces. These films provide a platform for ocular
      formulation of riboflavin, a drug used for corneal cross-linking in the treatment
      of keratoconus. An in vitro release of riboflavin as well as an in vivo retention
      of the films on corneal surfaces can be controlled by adjusting PAA/MC ratio in
      the formulations. 

PMID- 24106129
TI  - Nigerian bonny-light crude oil induces alteration in testicular stress response
      proteins and caspase-3 dependent apoptosis in albino wistar rats.
AB  - In the past few decades, there has been much concern about the adverse health
      effects of environmental contaminants in general and Crude Oil in particular
      around the Niger Delta region of Nigeria where all the crude Oil exploration is
      taking place. Studies have shown the repro-toxic effects of Bonny-light crude oil
      (BLCO). However, the insight into the mechanisms of gonadal toxicity induced by
      BLCO is not well known. In this study, we sought to elucidate the mechanism(s)
      underpinning the gonadal effects within hours of exposure to BLCO. Experimental
      rats were divided into five groups of four each. Animals were orally administered
      with a single dose of BLCO (800 mg/kg body weight) and killed at 0, 6, 12, 24,
      and 72 h post-treatment. The levels and time-course of induction of stress
      response proteins and apoptosis-related proteins like cytochorome C, caspase 3
      and procaspase 9, Fas-FasL, NF-kB and TNF-alpha were determined to assess
      sequential induction of apoptosis in the rat testis. DNA damage was assessed by
      TUNEL assay. Administration of BLCO resulted in a significant increase in the
      levels of stress response proteins and apoptotis- related proteins as early as 6
      h following exposure. Time-dependent elevations in the levels of the proteins
      were observed. The DNA damage was measured and showed time-dependent increase in
      the TUNEL positive cells of testicular cells. The study demonstrates induction of
      testicular apoptosis in adult rats following exposure to a single dose of BLCO.

PMID- 24106130
TI  - Pathogenicity phenomena in three model systems: from network mining to emerging
      system-level properties.
AB  - Understanding the interconnections of microbial pathogenicity phenomena, such as
      biofilm formation, quorum sensing and antimicrobial resistance, is a tremendous
      open challenge for biomedical research. Progress made by wet-lab researchers and
      bioinformaticians in understanding the underlying regulatory phenomena has been
      significant, with converging evidence from multiple high-throughput technologies.
      Notably, network reconstructions are already of considerable size and quality,
      tackling both intracellular regulation and signal mediation in microbial
      infection. Therefore, it stands to reason that in silico investigations would
      play a more active part in this research. Drug target identification and drug
      repurposing could take much advantage of the ability to simulate pathogen
      regulatory systems, host-pathogen interactions and pathogen cross-talking. Here,
      we review the bioinformatics resources and tools available for the study of the
      gram-negative bacterium Pseudomonas aeruginosa, the gram-positive bacterium
      Staphylococcus aureus and the fungal species Candida albicans. The choice of
      these three microorganisms fits the rationale of the review converging into
      pathogens of great clinical importance, which thrive in biofilm consortia and
      manifest growing antimicrobial resistance. 

PMID- 24106132
TI  - Age and sensory processing abnormalities predict declines in encoding and recall
      of temporally manipulated speech in high-functioning adults with ASD.
AB  - While temporal and perceptual processing abnormalities, identified in a number of
      electrophysiological and brain imaging studies of individuals with (ASD), are
      likely to impact on speech perception, surprisingly little is known about the
      behavioral outcomes of such abnormalities. It has been hypothesized that rapid
      temporal processing deficits may be linked to impaired language development
      through interference with acoustic information during speech perception. The
      present study aimed to investigate the impact of temporal changes on encoding and
      recall of speech, and the associated cognitive, clinical, and behavioral
      correlates in adults with ASD. Research carried out with typically developing
      (TD) adults has shown that word recall diminishes as the speed of speech
      increases, and it was predicted that the magnitude of this effect would be far
      greater in those with ASD because of a preexisting rapid temporal processing
      deficit. Nineteen high-functioning adults with ASD, and age- and intelligence
      matched TD controls performed verbatim recall of temporally manipulated
      sentences. Reduced levels of word recall in response to increases in presentation
      speed were observed, and this effect was greater in the older participants in the
      ASD group than in the control group. This is the first study to show that both
      sensory abnormalities and aging impact on speech encoding in ASD. Auditory
      processing deficits in ASD may be indicative of an association with the sensory
      abnormalities and social and communication impairments characterizing the
      disorder.

PMID- 24106131
TI  - Chemical and structural insights into the regioversatility of the aminoglycoside
      acetyltransferase Eis.
AB  - A recently discovered cause of tuberculosis resistance to a drug of last resort,
      the aminoglycoside kanamycin, results from modification of this drug by the
      enhanced intracellular survival (Eis) protein. Eis is a structurally and
      functionally unique acetyltransferase with an unusual capability of acetylating
      aminoglycosides at multiple positions. The extent of this regioversatility and
      its defining protein features are unclear. Herein, we determined the positions
      and order of acetylation of five aminoglycosides by NMR spectroscopy. This
      analysis revealed unprecedented acetylation of the 3''-amine of kanamycin,
      amikacin, and tobramycin, and the gamma-amine of the 4-amino-2-hydroxybutyryl
      group of amikacin. A crystal structure of Eis in complex with coenzyme A and
      tobramycin revealed how tobramycin can be accommodated in the Eis active site in
      two binding modes, consistent with its diacetylation. These studies, describing
      chemical and structural details of acetylation, will guide future efforts towards
      designing aminoglycosides and Eis inhibitors to overcome resistance in
      tuberculosis. 

PMID- 24106133
TI  - Permanent activation of HMGA2 in lipomas mimics its temporal physiological
      activation linked to the gain of adipose tissue.
AB  - OBJECTIVE: In this study the activation of HMGA2 and overexpression by FGF1
      driven stimulation of adipose tissue derived stem cells (ADSCs) in adipose tissue
      tumors were analyzed. In addition, the expression of HMGA2 and PPAR-gamma mRNA
      were quantified in canine subcutaneous abdominal adipose tissue from normal and
      overweight purebred dogs. DESIGN AND METHODS: ADSCs and adipose tissue explants
      stimulated with FGF1 followed by gene expression analyses of HMGA2 and p14(Arf)
      using Western-blot and qRT-PCR. Furthermore, canine subcutaneous white adipose
      tissue (WAT) were analyzed by qRT-PCR for their expression of HMGA2 and PPAR
      gamma. RESULTS: ADSCs and adipose tissue explants are able to execute a HMGA2
      response upon FGF1 stimulation. FGF1 enhances proliferation of ADSCs by a HMGA2
      dependent mechanism. In lipomas increase of HMGA2 is accompanied by increased
      expression of p14(Arf) . Furthermore, a significantly elevated level of HMGA2 in
      overweight dogs and a negative correlation between the expression of HMGA2 and
      PPAR-gamma in subcutaneous cWAT were noted. CONCLUSIONS: These results suggest
      that WAT contains cells that as essential part of adipogenesis up-regulate HMGA2
      resulting from growth factor stimulation. In subgroups of lipoma, constitutive
      activation of HMGA2 due to rearrangements replaces the temporal response
      triggered by growth factors.

PMID- 24106134
TI  - Does an Alzheimer's disease susceptibility gene influence the cognitive effects
      of cancer therapy?
AB  - The apolipoprotein E (APOE) e4 allele is the most prevalent genetic risk factor
      for Alzheimer's disease (AD). APOE e4 carriers suffer greater morbidity from head
      trauma, stroke, and carbon monoxide poisoning, yet possible interactions between
      APOE genotype and cancer therapy on cognition are unclear. Neuropathological and
      biomarker studies of young asymptomatic APOE e4 carriers that show elevated
      neocortical amyloid and medial temporal neurofibrillary tangles and longitudinal
      neuropsychological studies that show accelerated memory decline beginning around
      age 55-60 years define preclinical AD and have set the stage for assessing the
      potential adverse cognitive effects of cancer therapy in APOE e4 carriers.

PMID- 24106136
TI  - The in vivo effect of P-15 coating on early osseointegration.
AB  - The aim of this study was to evaluate mechanically and morphologically the effect
      of a specific peptide sequence P-15, when incorporated into implant surfaces.
      Three types of implants were used for the study: Group A: commercially pure
      titanium implant (blasted and acid etched) + electrochemical thin calcium
      phosphate deposition, Group B: commercially pure titanium implant (blasted and
      acid etched) + electrochemical thin calcium phosphate deposition + P-15
      incorporation, and as control, Group C: commercially pure titanium implant
      (blasted and acid etched). After a topographical characterization, transcortical
      osteotomies were made, and all implant groups (102 implants per group) were
      randomly placed bilaterally in the tibiae of adult beagle dogs (n = 24). At, 1,
      2, and 4 weeks post-surgery, the animals were sacrificed and the samples were
      retrieved for removal torque tests, for nano indentation, and for
      histomorphometrical analysis. The results (mean +/- 95% CI) showed that Group B
      (34.4 +/- 8.7%) presented statistically higher bone-to-implant contact than the
      other groups (A = 23.9 +/- 7.8%; C = 21.7 +/- 8.3%) at 1 week, indicating an
      enhanced osteogenesis due to the peptide incorporation. The results suggested
      that the incorporation of P-15 to implant surfaces increased its bioactivity and
      the effects were notable especially in the early stages of the healing process.

PMID- 24106135
TI  - Biopsychosocial typologies of pain in a cohort of patients with systemic
      sclerosis.
AB  - OBJECTIVE: Despite being a common problem in systemic sclerosis (SSc;
      scleroderma), the extant literature on pain has primarily focused on biomedical
      correlates, or bivariate relationships with a few psychological characteristics.
      There is a need to investigate the more heuristic biopsychosocial model, which
      incorporates the simultaneous contributions of medical, psychological, and social
      variables in understanding pain. METHODS: Patients with SSc (n = 333) received
      clinical examinations and completed self-report surveys at enrollment in the
      Genetics versus Environment in Scleroderma Outcome Study. Latent profile analysis
      was used to derive biopsychosocial profiles of patients using skin thickening,
      percent predicted forced vital lung capacity, perceived physical health, health
      worry, mental health, and social support. The profiles were examined in relation
      to pain and pain medication usage. RESULTS: A 3-profile solution provided the
      best fit to the data. Based on the biopsychosocial indicators, the profiles were
      characterized as managing (n = 217), resilient (n = 86), and distressed (n = 30).
      Between-group differences for pain emerged, with the distressed group, whose
      disease was less severe than the resilient group, reporting the highest pain and
      the greatest utilization of pain medication. CONCLUSION: Clinicians should
      consider biopsychosocial characteristics as contributing factors to the
      experience of pain in patients with SSc. Patients who are similar to those in the
      distressed profile may be at an increased risk for pain and would likely benefit
      from a referral to a behavioral health or other ancillary service provider for
      pain management, rather than relying solely on pharmacologic therapies.

PMID- 24106137
TI  - Preparation of pH-responsive polymer core-shell nanospheres for delivery of
      hydrophobic antineoplastic drug ellipticine.
AB  - Antineoplastic drug ellipticine and its derivatives are used in human cancer
      therapy. However, their clinical applications have been limited by its great
      hydrophobicity and severe side effects. An efficient delivery system is therefore
      very desirable. In this research, an ellipticine-loaded core-shell structured
      nanosphere namely poly(DEAEMA)-poly(PEGMA) is designed as a drug carrier and
      prepared via a two-step semibatch emulsion polymerization method where DEAEMA and
      PEGMA represent 2-(diethylamino)ethyl methacrylate and poly(ethylene glycol)
      methacrylate, respectively. The in-vitro release profiles of ellipticine towards
      the different pH liposome vesicles are recorded as a function of time at 37 
      degrees C. It is found that release of ellipticine from the core-shell polymer
      matrix is a pH-responsive and controlled release process. The three pH's of 3, 4,
      and 5 trigger a significant ellipticine release of 88% after 98 h, 83% after 98
      h, and 79% after 122 h, respectively. The release mechanism of ellipticine from
      the core-shell polymer matrix under acidic conditions is explored. The synthesis
      and encapsulation process developed herein provides a new perspective for the
      development of appropriate delivery systems to deliver the ellipticine and its
      analogues, as well as other types of hydrophobic drugs to a given target cell or
      tumor tissue. 

PMID- 24106138
TI  - Cationic bovine serum albumin based self-assembled nanoparticles as siRNA
      delivery vector for treating lung metastatic cancer.
AB  - It is generally believed that intravenous application of cationic vectors is
      limited by the binding of abundant negatively charged serum components, which may
      cause rapid clearance of the therapeutic agent from the blood stream. However,
      previous studies show that systemic delivery of cationic gene vectors mediates
      specific and efficient transfection within the lung, mainly as a result of
      interaction of the vectors with serum proteins. Based on these findings, a novel
      and charge-density-controllable siRNA delivery system is developed to treat lung
      metastatic cancer by using cationic bovine serum albumin (CBSA) as the gene
      vector. By surface modification of BSA, CBSA with different isoelectric points
      (pI) is synthesized and the optimal cationization degree of CBSA is determined by
      considering the siRNA binding and delivery ability, as well as toxicity. The CBSA
      can form stable nanosized particles with siRNA and protect siRNA from
      degradation. CBSA also shows excellent abilities to intracellularly deliver siRNA
      and mediate significant accumulation in the lung. When Bcl2-specific siRNA is
      introduced to this system, CBSA/siRNA nanoparticles exhibit an efficient gene
      silencing effect that induces notable cancer cell apoptosis and subsequently
      inhibits the tumor growth in a B16 lung metastasis model. These results indicate
      that CBSA-based self-assembled nanoparticles can be a promising strategy for a
      siRNA delivery system for lung targeting and metastatic cancer therapy.

PMID- 24106139
TI  - Simultaneous isocratic separation of phenolic acids and flavonoids using micellar
      liquid chromatography.
AB  - The simultaneous isocratic separation of a mixture of five phenolic acids and
      four flavonoids (two important groups of natural polyphenolic compounds with very
      different polarities) was investigated in three different RPLC modes using a
      hydro-organic mobile phase, and mobile phases containing SDS at concentrations
      below and above the critical micellar concentration (submicellar LC and micellar
      LC (MLC), respectively). In the hydro-organic mode, methanol and acetonitrile; in
      the submicellar mode methanol; and in the micellar mode, methanol and 1-propanol
      were examined individually as organic modifiers. Regarding the other modes, MLC
      provided more appropriate resolutions and analysis time and was preferred for the
      separation of the selected compounds. Optimization of separation in MLC was
      performed using an interpretative approach for each alcohol. In this way, the
      retention of phenolic acids and flavonoids were modeled using the retention
      factors obtained from five different mobile phases, then the Pareto optimality
      method was applied to find the best compatibility between analysis time and
      quality of separation. The results of this study showed some promising advantages
      of MLC for the simultaneous separation of phenolic acids and flavonoids,
      including low consumption of organic solvent, good resolution, short analysis
      time, and no requirement of gradient elution. 

PMID- 24106140
TI  - Genotoxicity risk assessment of diversely substituted quinolines using the SOS
      chromotest.
AB  - Quinolines are aromatic nitrogen compounds with wide therapeutic potential to
      treat parasitic and microbial diseases. In this study, the genotoxicity of
      quinoline, 4-methylquinoline, 4-nitroquinoline-1-oxide (4-NQO), and diversely
      functionalized quinoline derivatives and the influence of the substituents
      (functional groups and/or atoms) on their genotoxicity were tested using the SOS
      chromotest. Quinoline derivatives that induce genotoxicity by the formation of an
      enamine epoxide structure did not induce the SOS response in Escherichia coli
      PQ37 cells, with the exception of 4-methylquinoline that was weakly genotoxic.
      The chemical nature of the substitution (C-5 to C-8: hydroxyl, nitro, methyl,
      isopropyl, chlorine, fluorine, and iodine atoms; C-2: phenyl and 3,4
      methylenedioxyphenyl rings) of quinoline skeleton did not significantly modify
      compound genotoxicities; however, C-2 substitution with alpha-, beta-, or gamma
      pyridinyl groups removed 4-methylquinoline genotoxicity. On the other hand, 4-NQO
      derivatives whose genotoxic mechanism involves reduction of the C-4 nitro group
      were strong inducers of the SOS response. Methyl and nitrophenyl substituents at
      C-2 of 4-NQO core affected the genotoxic potency of this molecule. The relevance
      of these results is discussed in relation to the potential use of the substituted
      quinolines. The work showed the sensitivity of SOS chromotest for studying
      structure-genotoxicity relationships and bioassay-guided quinoline synthesis.

PMID- 24106141
TI  - Cadazolid, a novel antibiotic with potent activity against Clostridium difficile:
      safety, tolerability and pharmacokinetics in healthy subjects following single
      and multiple oral doses.
AB  - OBJECTIVES: Current treatment options for Clostridium difficile-associated
      diarrhoea (CDAD) leave a high unmet medical need for new therapies. Cadazolid is
      a new antibiotic in development for the treatment of CDAD. The objectives of this
      study were to evaluate its tolerability and pharmacokinetics following single
      ascending doses (AC-061-101) and multiple ascending doses (AC-061-102). METHODS:
      Single and multiple (twice daily for 10 days) oral doses of cadazolid between 30
      mg and 3000 mg, or placebo, were tested in a total of 64 healthy male subjects.
      Safety assessments were conducted at regular intervals. Blood, urine and faeces
      were sampled, and cadazolid concentrations were measured. RESULTS: Cadazolid was
      well tolerated up to 3000 mg given twice daily for 10 days. The most common
      adverse event was headache, with no observed relationship between dose or
      treatment duration and adverse events. Plasma concentrations of cadazolid were
      low. No plasma concentrations >3.3 ng/mL were observed after single doses or >6.9
      ng/mL after 10 days of multiple doses. Food increased the mean C(max) from 0.73
      to 1.87 ng/mL and mean AUC(0-t) from 3.13 to 15.69 ng .h/mL after a single 300 mg
      dose. The increase in systemic exposure to cadazolid across doses was less than
      dose-proportional. The mean cumulative faecal recovery was 81.0%-93.5%. Urinary
      recovery of unchanged compound was <0.015%. CONCLUSIONS: Cadazolid was well
      tolerated and its systemic exposure was low. The majority of compound was
      recovered unchanged in the faeces, thus resulting in high concentrations at the
      site of action (colon).

PMID- 24106143
TI  - Dating violence and posttraumatic stress disorder symptoms in Taiwanese college
      students: the roles of cultural beliefs.
AB  - This study has examined the effects that young adults' experience of dating
      violence victimization can have on their manifestation of posttraumatic stress
      disorder (PTSD) symptoms. This study has also examined the possible roles that
      cultural beliefs can play in dating-violence experience, coping choices, and PTSD
      symptoms. This study has used self-reporting measures to collect data from a
      nationally stratified random sample of 1,018 college students in Taiwan. Results
      demonstrate that college students who had experienced dating-violence
      victimization reported higher levels of PTSD symptoms than those who had not. The
      results reveal that psychological-violence victimization and cultural beliefs
      have direct and indirect effects on PTSD symptoms via the mediation of young
      adults' use of emotion-focused coping strategies. Greater frequencies of
      psychological-violence victimization were associated with a greater use of
      emotion-focused coping, which was in turn associated with increases in PTSD
      symptoms. This study illustrates that traditional Chinese beliefs have played
      significant roles in exacerbating the risk for dating violence and PTSD, and in
      shaping victims' coping choices with dating violence. 

PMID- 24106142
TI  - Ralfuranone thioether production by the plant pathogen Ralstonia solanacearum.
AB  - Ralfuranones are aryl-substituted furanone secondary metabolites of the Gram
      negative plant pathogen Ralstonia solanacearum. New sulfur-containing ralfuranone
      derivatives were identified, including the methyl thioether-containing
      ralfuranone D. Isotopic labeling in vivo, as well as headspace analyses of
      volatiles from R. solanacearum liquid cultures, established a mechanism for the
      transfer of an intact methylthio group from L-methionine or alpha-keto-gamma
      methylthiobutyric acid. The methylthio acceptor molecule ralfuranone I, a
      previously postulated biosynthetic intermediate in ralfuranone biosynthesis, was
      isolated and characterized by NMR. The highly reactive Michael acceptor system of
      this intermediate readily reacts with various thiols, including glutathione. 

PMID- 24106144
TI  - Israeli mothers' willingness to use corporal punishment to correct the
      misbehavior of their elementary school children.
AB  - The present study theoretically and methodologically specifies and expands the
      concept of child misbehavior of the study of corporal punishment (CP). It
      introduced a new concept and measure designated "Willingness to Use CP." The
      findings of this study provide initial support for the validity and reliability
      of this measure among 204 Israeli mothers with at least one child in the first or
      second elementary school grade. These findings also indicate that the measure is
      affected by the extent to which the misbehavior offends the mother and by the
      risk it puts the child in. However, the weight of the former was higher than the
      latter. It appears that the extent to which the mother feels offended depends on
      the distance between her and the focus of offense of her child's misbehavior: The
      closer it is to the mother, the more offended she feels and her willingness to
      use CP increases. Findings also indicate that there is a strong association
      between willingness to use and actual use of CP, regardless of appropriateness of
      child behavior, child gender, and family socioeconomic status. These findings
      support not only the reliability and validity of this new measure but also its
      relevance for the study of CP. 

PMID- 24106145
TI  - Understanding the relationship between proactive and reactive aggression, and
      cyberbullying across United States and Singapore adolescent samples.
AB  - This study examined cyberbullying among adolescents across United States and
      Singapore samples. Specifically, the purpose of the investigation was to study
      the differential associations between proactive and reactive aggression, and
      cyberbullying across two cultures. A total of 425 adolescents from the United
      States (M age = 13 years) and a total of 332 adolescents from Singapore (M age =
      14.2 years) participated in the study. Results of the moderator analyses
      suggested that nationality was not a moderator of the relationship between
      proactive aggression and cyberbullying, and between reactive aggression and
      cyberbullying. As expected, findings showed proactive aggression to be positively
      associated with cyberbullying, after controlling for reactive aggression, across
      both samples. Likewise, as hypothesized, reactive aggression and cyberbullying
      was not found to be significant after controlling for proactive aggression across
      both samples. Implications of these findings were discussed: (a) Proactive
      aggression is a possible risk factor for both bullying and cyberbullying; (b)
      proactive and reactive aggression could be argued to be distinct as they have
      different correlates-only proactive aggression contributed to cyberbullying after
      controlling for reactive aggression; (c) this research extends previous work and
      contributes toward cross-cultural work using similar and comparable measures
      across different samples; and (d) prevention and intervention programs targeted
      at proactive aggressive adolescents could adopt a two-pronged approach by
      changing mind sets, and by understanding and adopting a set of rules for Internet
      etiquette. 

PMID- 24106147
TI  - Sex-role identification and violent victimization: gender differences in the role
      of masculinity.
AB  - Although sex-role identification has been found to be associated with crime and
      delinquency, the link between sex-role identification and violent victimization
      has remained largely unexplored. Using the Add Health data, this study examines
      sex-role identification and its relationship to violent victimization. The
      findings suggest that masculinity increases the risk of violent victimization for
      males, but does not for females. Other differences in risk factors across gender
      were also found. These findings indicate that masculinity is an important
      construct in understanding the complexity of why some persons are violently
      victimized and others are not. 

PMID- 24106146
TI  - Quantifying discipline practices using absolute versus relative frequencies:
      clinical and research implications for child welfare.
AB  - In the parent intervention outcome literatures, discipline practices are
      generally quantified as absolute frequencies or, less commonly, as relative
      frequencies. These differences in methodology warrant direct comparison as they
      have critical implications for study results and conclusions among treatments
      targeted at reducing parental aggression and harsh discipline. In this study, we
      directly compared the absolute frequency method and the relative frequency method
      for quantifying physically aggressive, psychologically aggressive, and
      nonaggressive discipline practices. Longitudinal data over a 3-year period came
      from an existing data set of a clinical trial examining the effectiveness of a
      psychosocial treatment in reducing parental physical and psychological aggression
      and improving child behavior (N = 139). Discipline practices (aggressive and
      nonaggressive) were assessed using the Conflict Tactics Scale. The two methods
      yielded different patterns of results, particularly for nonaggressive discipline
      strategies. We suggest that each method makes its own unique contribution to a
      more complete understanding of the association between parental aggression and
      intervention effects. 

PMID- 24106148
TI  - Attachment style, early sexual intercourse, and dating aggression victimization.
AB  - The present study examined relations between attachment style, age at first
      sexual intercourse, and dating aggression (DA) victimization. In all, 137
      heterosexual female undergraduate students 18 to 25 years of age (M = 20.76, SD =
      1.87) completed an online questionnaire that included questions regarding sexual
      history, attachment style (Experiences in Close Relationships Scale), and DA
      (Conflict in Adolescent Dating Relationships Inventory). Initial bivariate
      correlations revealed that women reported higher rates of DA victimization if
      they were more anxiously attached (r = .30, p = .000), had an earlier age at
      vaginal sexual debut (r = -.19, p = .015), and had an earlier age at oral sexual
      debut (r = -.15, p = .046); however, when entered into a predictive multivariate
      model, neither the addition of anxious attachment nor an early age at sexual
      debut accounted for a significant amount of variance above and beyond control
      variables. Although we were unable to affirm anxious attachment and an early age
      at first intercourse as risk factors for DA victimization, posthoc analyses
      emphasized the need to control for social desirability when gathering information
      on sensitive topics in clinical and research settings. 

PMID- 24106149
TI  - Predicting cellulose solvating capabilities of acid-base conjugate ionic liquids.
AB  - Different acid-base conjugates were made by combining a range of bases and
      superbases with acetic and propionic acid. Only the combinations that contained
      superbases were capable of dissolving cellulose. Proton affinities were
      calculated for the bases. A range, within which cellulose dissolution occurred,
      when combined with acetic or propionic acid, was defined for further use. This
      was above a proton affinity value of about 240 kcal mol(-1) at the MP2/6
      311+G(d,p)//MP2/ 6-311+G(d,p) ab initio level. Understanding dissolution allowed
      us to determine that cation acidity contributed considerably to the ability of
      ionic liquids to dissolve cellulose and not just the basicity of the anion. By
      XRD analyses of suitable crystals, hydrogen bonding interactions between anion
      and cation were found to be the dominant interactions in the crystalline state.
      From determination of viscosities of these conjugates over a temperature range,
      certain structures were found to have as low a viscosity as 1-ethyl-3
      methylimidazolium acetate, which was reflected in their high rate of cellulose
      dissolution but not necessarily the quantitative solubility of cellulose in those
      ionic liquids. 1,5-Diazabicyclo[4.3.0]non-5-enium propionate, which is one of the
      best structures for cellulose dissolution, was then distilled using laboratory
      equipment to demonstrate its recyclability. 

PMID- 24106150
TI  - Longitudinal (one-year) change in cartilage thickness in knees with early knee
      osteoarthritis: A within-person between-knee comparison.
AB  - Objective: To test the hypothesis that cartilage displays significant
      longitudinal thickening in the external subregions of the central medial (ecMF)
      and lateral (ecLF) femur in knees with early radiographic osteoarthritis (ROA)
      compared with contralateral knees without ROA, and to explore differences in
      change in other subregions and in radiographic joint space width (JSW). Methods:
      50 participants (50% women; age 61.1+/-9.7y; BMI 27.7+/-4.7kg/m2 ) were
      identified from the Osteoarthritis Initiative cohort with definite femorotibial
      osteophytes but no JSN in one knee (early ROA), and no osteophytes or JSN in the
      contralateral knee (non-ROA). A longitudinal within-person, between-knee
      comparison was performed using measures of subregional cartilage thickness based
      on analyses of sagittal DESSwe MR images obtained at baseline and 1-year. Medial
      JSW was evaluated from fixed flexion radiographs. Results: The change between
      baseline and 1-year was -6+/-94um in ecMF and +18+/-91um in ecLF in early ROA
      (p=0.78) vs. -1+/-68um and +4+/-76um in non-ROA knees (p=0.38). The variability
      of cartilage thickness change tended to be greater in early ROA than in non-ROA
      knees. Greater cartilage thickness loss in the lateral tibia and a greater
      reduction in minimum medial JSW was observed in early ROA vs. non-ROA knees.
      Conclusion: There was no direct evidence of longitudinal cartilage thickening in
      external subregions of the central femur in knees with early ROA compared with
      contralateral non-ROA knees. The observed greater variability in longitudinal
      thickness change in early ROA knees (but not in non-ROA knees) might be due to
      cartilage thickening and thinning occurring simultaneously in these knees.

PMID- 24106151
TI  - Evidence of yttrium silicate inclusions in YSZ-porcelain veneers.
AB  - This report introduces the discovery of crystalline defects that can form in the
      porcelain veneering layer when in contact with yttria-stabilized zirconia (YSZ).
      The focus was on dental prostheses and understanding the defects that form in the
      YSZ/porcelain system; however the data reported herein may have broader
      implications toward the use and stability of YSZ-based ceramics in general.
      Specimens were cut from fully sintered YSZ plates and veneering porcelain was
      applied (<1 mm thick) to one surface and fired under manufacturer's recommended
      protocol. Scanning electron microscopy (SEM) with integrated electron dispersive
      X-ray (EDAX) was used for microstructural and elemental analysis. EDAX, for
      chemical analysis and transmission electron diffraction (TED) for structural
      analysis were both performed in the transmission electron microscope (TEM).
      Additionally, in order to spatially resolve Y-rich precipitates, micro-CT scans
      were conducted at varying depths within the porcelain veneer. Local EDAX (SEM)
      was performed in the regions of visible inclusions and showed significant
      increases in yttrium concentration. TEM specimens also showed apparent inclusions
      in the porcelain and selected area electron diffraction was performed on these
      regions and found the inclusions to be crystalline and identified as either
      yttrium-silicate (Y2 SiO5 ) or yttrium-disilicate (Y2 Si2 O7 ). Micro-CT data
      showed that yttrium-silicate precipitates were distributed throughout the
      thickness of the porcelain veneer. Future studies are needed to determine whether
      many of the premature failures associated with this materials system may be the
      result of crystalline flaws that form as a result of high temperature yttrium
      diffusion near the surfaces of YSZ.

PMID- 24106152
TI  - pH- and redox-responsive poly(ethylene glycol) and cholesterol-conjugated
      poly(amido amine)s based micelles for controlled drug delivery.
AB  - An optimized condition is identified to prepare linear poly(amido amine)s via
      Michael Addition polymerization of trifunctional amine, 4-(aminomethyl)piperidine
      (AMPD), with an equimolar diacrylamide, N,N-cystaminebis(acrylamide) (BAC).
      Poly(ethylene glycol) (PEG) and cholesterol (CE) are conjugated to linear
      poly(BAC-AMPD) through the reactions with the secondary amino groups in the
      backbone, respectively, to form poly(BAC-AMPD)-g-PEG-g-CE. The chemical
      structures of poly(BAC-AMPD) and poly(BAC-AMPD)-g-PEG-g-CE are characterized
      using NMR and gel permeation chromatography (GPC). Transmission electron
      microscopy (TEM), dynamic light scattering (DLS) and (1)H NMR results show that
      micelles with PEG shells and hydrophobic cores composed of poly(BAC-AMPD) and CE
      are formed via self-assembly of poly(BAC-AMPD)-g-PEG-g-CE in aqueous solution,
      and the micelles of poly(BAC-AMPD)-g-PEG-g-CE can be degraded by the presence of
      L-dithiothreitol and show a limited cytotoxicity in vitro. The anti-cancer drug,
      doxorubicin (DOX), can be loaded into the micelles. The DOX loaded micelles of
      poly(BAC-AMPD)-g-PEG-g-CE show pH- and redox-responsive drug release and redox
      induced formation of aggregates, and it is shown that the DOX loaded micelles can
      deliver DOX into cells and show a higher efficacy in killing cancer cells than
      free drug.

PMID- 24106154
TI  - Preparation and application of carbon nanotubes/poly(o-toluidine) composite
      fibers for the headspace solid-phase microextraction of benzene, toluene,
      ethylbenzene, and xylenes.
AB  - A novel nanocomposite coating of poly(o-toluidine) and oxidized multiwalled CNTs
      (MWCNTs, where CNTs is carbon nanotubes) was electrochemically prepared on a
      stainless-steel wire. The applicability of the fiber was assessed for the
      headspace solid-phase microextraction of benzene, toluene, ethylbenzene, and
      xylenes in aqueous samples followed by GC with flame ionization detection. In
      order to obtain an adherent and stable composite coating, several experimental
      parameters related to the coating process, such as polymerization potential and
      time, and the concentration of o-toluidine and oxidized MWCNTs were optimized.
      The combination of MWCNTs and polymer in a nanocomposite form presents desirable
      opportunities to produce materials for new applications. The effects of various
      parameters on the efficiency of the headspace solid-phase microextraction
      process, such as desorption temperature and time, extraction temperature and
      time, and ionic strength were also investigated. At the optimum conditions, LODs
      were 0.03-0.06 MUg/L. The method showed linearity in the range of 0.5-300 MUg/L
      with coefficients of determination >0.99. The intraday and interday RSDs obtained
      at a 5 MUg/L concentration level (n = 5) using a single fiber were 1.2-5.2 and
      3.2-7.5%, respectively. The fiber-to-fiber RSD (%; n = 3) at 5 MUg/L was 6.1
      9.2%. 

PMID- 24106155
TI  - Direct intermolecular force measurements between functional groups and individual
      metallic or semiconducting single-walled carbon nanotubes.
AB  - Many electronic applications of single-walled carbon nanotubes (SWNTs) require
      electronic homogeneity in order to maximally exploit their outstanding
      properties. Non-covalent separation is attractive as it is scalable and results
      in minimal alteration of nanotube properties. However, fundamental understanding
      of the metallicity-dependence of functional group interactions with nanotubes is
      still lacking; this lack is compounded by the absence of methods to directly
      measure these interactions. Herein, a novel technology platform based on a
      recently developed atomic force microscopy (AFM) mode is reported which directly
      quantifies the adhesion forces between a chosen functional group and individual
      nanotubes of known metallicity, permitting comparisons between different
      metallicity. These results unambiguously show that this technology platform is
      able to discriminate the subtle adhesion force differences of a chosen functional
      group with pure metallic as opposed to pure semiconducting nanotubes. This new
      method provides a route towards rapid advances in understanding of non-covalent
      interactions of large libraries of compounds with nanotubes of varying
      metallicity and diameter; presenting a superior tool to assist the discovery of
      more effective metallicity-based SWNT separation agents. 

PMID- 24106153
TI  - Clofarabine salvage therapy in refractory multifocal histiocytic disorders,
      including Langerhans cell histiocytosis, juvenile xanthogranuloma and Rosai
      Dorfman disease.
AB  - BACKGROUND: Existing therapies for recurrent or refractory histiocytoses,
      including Langerhans cell histiocytosis (LCH), juvenile xanthogranuloma (JXG),
      and Rosai-Dorfman disease (RDD), have limited effectiveness. We report our
      experience with using clofarabine as therapy in children with recurrent or
      refractory histiocytic disorders, including LCH (11 patients), systemic JXG (4
      patients), and RDD (3 patients). METHODS: Patients treated with clofarabine for
      LCH, JXG, or RDD by Texas Children's Hospital physicians or collaborators between
      May 2011 and January 2013 were reviewed for response and toxicity. RESULTS:
      Patients were treated with a median of three chemotherapeutic regimens prior to
      clofarabine. Clofarabine was typically administered at 25 mg/m(2) /day for 5
      days. Cycles were administered every 28 days for a median of six cycles (range: 2
      8 cycles). Seventeen of 18 patients are alive. All surviving patients showed
      demonstrable improvement after two to four cycles of therapy, with 11 (61%)
      complete responses, 4 (22%) partial responses, and 2 patients still receiving
      therapy. Five patients experienced disease recurrence, but three of these
      subsequently achieved complete remission. All patients with JXG and RDD had
      complete or partial response at conclusion of therapy. Side effects included
      neutropenia in all patients. Recurring but sporadic toxicities included prolonged
      neutropenia, severe vomiting, and bacterial infections. CONCLUSION: Clofarabine
      has activity against LCH, JXG, and RDD in heavily pretreated patients, but
      prospective multi-center trials are warranted to determine long-term efficacy,
      optimal dosing, and late toxicity of clofarabine in this population.

PMID- 24106156
TI  - Pyranonigrin E: a PKS-NRPS hybrid metabolite from Aspergillus niger identified by
      genome mining.
AB  - Induced production of PKS-NRPS metabolites: the genome mining approach is useful
      for obtaining new compounds. We activated a dormant PKS-NRPS gene cluster in
      Aspergillus niger ATCC 1015 by expressing its dedicated transcriptional activator
      (PynR). As a result, the transformant expressing pynR produced a new pyranonigrin
      compound that we have named pyranonigirin E.

PMID- 24106157
TI  - Overall and cause-specific mortality in patients with systemic lupus
      erythematosus: a meta-analysis of observational studies.
AB  - OBJECTIVE: To determine the magnitude of risk from all-cause and cause-specific
      mortality in patients with systemic lupus erythematosus (SLE) compared to the
      general population through a meta-analysis of observational studies. METHODS: We
      searched the Medline and Embase databases from their inception to October 2011.
      Observational studies that met the following criteria were assessed: 1) a
      prespecified SLE definition; 2) overall and/or cause-specific deaths, including
      cardiovascular disease (CVD), infections, malignancy, and renal disease; and 3)
      reported standardized mortality ratios (SMRs) and 95% confidence intervals (95%
      CIs). We calculated weighted-pooled summary estimates of SMRs (meta-SMRs) for all
      cause and cause-specific mortality using the random-effects model and tested for
      heterogeneity using the I(2) statistic by using Stata/IC statistical software.
      RESULTS: We identified 12 studies comprising 27,123 patients with SLE (4,993
      observed deaths) that met the inclusion criteria. Overall, there was a 3-fold
      increased risk of death in patients with SLE (meta-SMR 2.98, 95% CI 2.32-3.83)
      when compared with the general population. The risks of death due to CVD (meta
      SMR 2.72, 95% CI 1.83-4.04), infection (meta-SMR 4.98, 95% CI 3.92-6.32), and
      renal disease (SMR 7.90, 95% CI 5.50-11.00) were significantly increased.
      Mortality due to malignancy was the only cause-specific entity not increased in
      SLE (meta-SMR 1.19, 95% CI 0.89-1.59). CONCLUSION: The published data indicated a
      3-fold increase in all-cause mortality in patients with SLE compared to the
      general population. Additionally, all cause-specific mortality rates were
      increased except for malignancy, with renal disease having the highest mortality
      risk.

PMID- 24106158
TI  - Molecular relaxations in magnesium polymer electrolytes via GHz broadband
      electrical spectroscopy.
AB  - GHz broadband electrical spectroscopy (G-BES) is adopted to investigate the
      molecular relaxations and interactions occurring within the system in an oxygen-
      and water-free atmosphere in the 300 kHz-20 GHz and -40 to 250  degrees C
      frequency and temperature ranges, respectively. A new electrolyte for magnesium
      secondary batteries that can transfer magnesium ions efficiently is presented.
      This electrolyte is based on polyethylene glycol 400 and a polymeric form of
      delta-MgCl2 . The information obtained by G-BES is crucial for studying the
      conduction mechanism of these new electrolytes. 

PMID- 24106159
TI  - Pt-Al2O3 interfaces in cofired ceramics for use in miniaturized neuroprosthetic
      implants.
AB  - A core element to miniaturized, hermetic encapsulations for neuroprosthetic
      implants with high numbers of stimulation channels is the creation of electrical
      feedthroughs. Platinum (Pt) and alumina (Al2 O3 ) are necessary to connect the
      sealed electronics to external components including electrode arrays that provide
      a neural interface function, as well as to sources of power or data. Combined
      with laser micro-processing, high-density feedthrough arrays were created with up
      to 2500 channels per cm(2) . The chemistry, micro structure, and crystallography
      of the Pt-Al2 O3 interface created by the cofiring of Pt particles and Al2 O3
      particulate in binder were studied by transmission electron microscopy (TEM),
      energy dispersive spectroscopy (EDS) and selective area electron diffraction
      (SAED) to determine the nature of the Pt-Al2 O3 bond. While Pt-Al2 O3 interfaces
      only occurred in cases where the different grains were in distinct orientations
      where the crystal lattices matched, the addition of glass additives allowed for
      bonding nonmatching orientations by devitrification to form Pt-glass-Al2 O3
      interfaces. The conditions for the formation of both mechanisms were determined,
      and it was shown that higher order crystal planes than previously described can
      be matched. Analyzing the lattice matches in detail showed the ability of the
      material compound to compensate for mismatches by the formation of dislocations,
      out-of-angle matching, lattice distortion, and the existence of semi-coherent
      interfaces in case of integer misfit ratios to create domain matching.

PMID- 24106160
TI  - A comparison of pediatric, adolescent, and adult testicular germ cell malignancy.
AB  - BACKGROUND: Testicular germ cell tumors (T-GCTs) occur from infancy to adulthood,
      and are the most common solid tumor in adolescent and young adult males.
      Traditionally, pediatric T-GCTs were perceived as more indolent than adult T
      GCTs. However, there are few studies comparing these groups and none that
      specifically evaluate adolescents. METHODS: An institutional database of T-GCT
      patients was reviewed and patients were categorized into Pediatric, aged 0-12
      years, Adolescent, aged 13-19 years, and Adult, older than 20 years, cohorts.
      Demographics, tumor characteristics, disease stage, treatment, event-free
      survival (EFS), and overall survival (OS) were compared between groups. RESULTS:
      Overall, 413 patients (20 pediatric, 39 adolescent, 354 adult) met study criteria
      and were followed for a median of 2.0 years (0.1-23.6). Adolescents presented
      with more advanced stage than children (P = 0.018) or adults (P = 0.008). There
      was a higher rate of events in Adolescents (13, 33.3%) than in Adults (61, 17.2%)
      or Children (2, 10.0%). Three-year EFS was 87.2% in the Pediatric group, 59.9% in
      Adolescents and 80.0% in Adults (P = 0.011). In a multivariate analysis,
      controlling for stage, IGCCCG risk, and histology, the hazard ratio (HR) for an
      event was: 1 (Reference) for Adults, HR = 0.82 (95% CI 0.19-3.46; P = 0.33) for
      the Pediatric group, and HR = 2.22 (95% CI 1.21-4.07; P = 0.01) for Adolescents.
      Five-year OS was 100% in the Pediatric group, 84.8% in Adolescents, and 92.8% in
      Adults (P = 0.388). CONCLUSION: Lower EFS in adolescent T-GCT patients was
      observed than in either children or adults. Elucidating factors associated with
      inferior outcomes in adolescents is an important focus of future research.

PMID- 24106161
TI  - Magnetic separation of heavy metal ions and evaluation based on surface-enhanced
      Raman spectroscopy: copper(II) ions as a case study.
AB  - A new approach was developed for the magnetic separation of copper(II) ions with
      easy operation and high efficiency. p-Mercaptobenzoic acid served as the modified
      tag of Fe2O3@Au nanoparticles both for the chelation ligand and Raman reporter.
      Through the chelation between the copper(II) ions and carboxyl groups on the gold
      shell, the Fe2O3@Au nanoparticles aggregated to form networks that were enriched
      and separated from the solution by a magnet. A significant decrease in the
      concentration of copper(II) ions in the supernatant solution was observed. An
      extremely sensitive method based on surface-enhanced Raman spectroscopy was
      employed to detect free copper(II) ions that remained after the magnetic
      separation, and thus to evaluate the separation efficiency. The results indicated
      the intensities of the surface-enhanced Raman spectroscopy bands from p
      mercaptobenzoic acid were dependent on the concentration of copper(II) ions, and
      the concentration was decreased by several orders of magnitude after the magnetic
      separation. The present protocol effectively decreased the total amount of heavy
      metal ions in the solution. This approach opens a potential application in the
      magnetic separation and highly sensitive detection of heavy metal ions.

PMID- 24106162
TI  - Characteristics of the ideal postgraduate year 1 pharmacy practice residency
      candidate: a survey of residency program directors.
AB  - OBJECTIVE: Assess pharmacy postgraduate year 1 (PGY1) residency application
      statistics and identify the qualities most desired in the ideal pharmacy
      residency candidate. METHODS: A list of PGY1 residency program directors across
      the United States (n = 750) was acquired, and a validated electronic survey was
      created. The survey contained 25 questions pertaining to program demographics,
      application statistics, and candidate characteristics. RESULTS: A total of 252
      programs completed the survey. The average number of positions per program was
      3.4 +/- 2.6. The average ratio of applicants to available positions was 15:1. The
      highest scored quality was familiarity with an applicant's college of pharmacy
      (7.7 +/- 2.5). Holding a leadership position within the college/university scored
      6.5 +/- 2, while poster presentations and publications were rated lower (4.1 +/-
      2.5 and 3.1 +/- 2.3, respectively). When asked to rank modifiable
      characteristics, strong letters of recommendation, letters of intent, and prior
      experience with the applicant were ranked the highest. CONCLUSIONS: Strong
      letters of recommendation and intent along with prior experience with an
      applicant are highly valued. Although leadership positions and scholarship are
      not ranked as highly, they may distinguish applicants if the preceding criteria
      are met. Applicants should strive to build relationships with preceptors and
      obtain work experience or experiential rotations at potential residency
      locations.

PMID- 24106163
TI  - Perceptions of a continuing professional development portfolio model to enhance
      the scholarship of teaching and learning.
AB  - OBJECTIVE: To obtain feedback about the potential usefulness of a continuing
      professional development (CPD) portfolio for enhancing a faculty or
      practitioner's scholarship of teaching and learning (SoTL). METHOD: A CPD
      portfolio approach to the SoTL was distributed in advance to registrants of the
      2011 Annual AACP Teacher's Seminar. In an interactive workshop, faculty
      facilitators described a model for a CPD process applied to the development of an
      individual's SoTL. During the workshop, participants were asked to complete the
      initial sections of the portfolio to develop a personal plan for success in the
      SoTL. Post workshop, an evaluation form was distributed to the participants to
      obtain feedback about the CPD approach. Completed evaluation forms were
      collected, collated, and summarized. RESULTS: A total of 53 (14.1%) workshop
      participants completed the evaluation form of the 375 attendees. In all, 25
      assistant professors, 14 associate professors, 4 full professors, 10
      residents/students, 22 clinical, and 2 research faculty submitted evaluations.
      The proposed uses for the portfolio model selected most often by the responders
      were for personal development, faculty evaluation, increasing the SoTL, new
      faculty development, preceptor development, and residency training. IMPLICATIONS:
      A structured CPD portfolio model might be useful for the professional development
      of the SoTL.

PMID- 24106164
TI  - Targeted theranostic nanoparticles: receptor-mediated entry into cells, pH
      induced signal generation and cytosolic delivery.
AB  - Virus-like theranostic nanoparticles: virus-like poly(amino acid) nanoparticles
      are synthesized that can be internalized via receptor-mediated endocytosis,
      resulting in encapsulated pH-activatable fluorescence probes that can be turned
      on in acidic environments but otherwise remain undetectable. The encapsulated
      anticancer drugs are also released into cytosol by endosome disruption. 

PMID- 24106165
TI  - G-quadruplexes as tools for synthetic biology.
AB  - With the potential to engineer biological systems, synthetic biology is an
      emerging field that combines various disciplines of sciences. It encompasses
      combinations of DNA, RNA and protein modules for constructing desired systems and
      the "rewiring" of existing signalling networks. Despite recent advances, this
      field still lags behind in the artificial reconstruction of cellular processes,
      and thus demands new modules and switches to create "genetic circuits". The
      widely characterised noncanonical nucleic acid secondary structures, G
      quadruplexes are promising candidates to be used as biological modules in
      synthetic biology. Structural plasticity and functional versatility are
      significant G-quadruplex traits for its integration into a biological system and
      for diverse applications in synthetic circuits. 

PMID- 24106166
TI  - Pb2+ induced IL-8 gene expression by extracellular signal-regulated kinases and
      the transcription factor, activator protein 1, in human gastric carcinoma cells.
AB  - Divalent lead (Pb(2+) ) is a common industrial pollutant epidemiologically
      associated with gastric cancers. Pb(2+) was found to promote tumorigenesis, which
      may include interleukin (IL)-8, a pro-inflammatory chemokine that promotes
      angiogenesis and tumor metastasis. Given that the gastrointestinal tract is a
      major route of Pb(2+) exposure, we investigated the ability of Pb(2+) to induce
      IL-8 expression in gastric carcinoma cells and its underlying mechanism. At a
      concentration of 0.1 MUM, Pb(2+) induced IL-8 gene activation in gastric
      carcinoma AGS cells. Using a IL-8 promoter-deletion analysis, transcription
      factor activator protein 1 (AP-1) was identified as a necessary component of
      Pb(2+) -induced IL-8 gene activation. Upregulation of the IL-8 gene was abrogated
      by the MEK inhibitor, PD98059, and partially suppressed by the epidermal growth
      factor receptor inhibitors, AG1478 and PD153035. Furthermore, c-Jun protein
      expression was induced in cells treated with Pb(2+) , and overexpression of c-Jun
      enhanced Pb(2+) -induced IL-8 activation. Collectively, our findings highlight
      the pivotal roles of AP-1 and extracellular signal-regulated kinase in signal
      transduction of Pb(2+) -induced IL-8 gene activation. These molecules may be
      potential therapeutic targets for Pb(2+) -related inflammation leading to stomach
      carcinogenesis. (c) 2013 Wiley Periodicals, Inc. Environ Toxicol 30: 315-322,
      2015. 

PMID- 24106167
TI  - Radiologic patterning of joint damage to the foot in rheumatoid arthritis.
AB  - OBJECTIVE: Foot and ankle deformities greatly affect the quality of life of
      rheumatoid arthritis (RA) patients. The aim of this study was to elucidate the
      pattern of destruction of the RA foot and its impact on patients. METHODS: We
      cross-sectionally investigated RA patients (274 patients and 542 feet) using
      radiographs. The grade of joint destruction was assigned using Larsen's grading
      system for 12 joints in the foot and ankle. Cluster analysis was performed using
      the K-means method to classify the pattern of joint destruction. Of the 274
      patients evaluated radiographically, 212 were assessed for functional disability
      using questionnaires. RESULTS: Cluster analysis revealed that 542 feet were
      divided into 5 clusters, named according to the characteristic distribution of
      joint destruction: cluster I (normal type), cluster II (forefoot type), cluster
      III (midfoot type), cluster IV (mid-hindfoot type), and cluster V (combined
      type). Radiographic measurements revealed the characteristic deformities of each
      cluster: splay foot for cluster II, flat foot for cluster III, hindfoot
      malalignment for cluster IV, and mixtures of these characteristics for cluster V.
      A distribution map of each cluster based on disease duration revealed that
      cluster III peaked in cases of 5-10-year disease duration and subsequently
      decreased, followed by a gradual increase of cluster IV and cluster V. Cluster IV
      and cluster V showed significant changes in functional disability compared to
      cluster III. CONCLUSION: This report is the first to reveal the pattern of RA
      foot deformities and their impact on patients using statistical measures in a
      large series.

PMID- 24106168
TI  - Efficiency enhancement of dye-sensitized solar cells by the addition of an
      oxidizing agent to the TiO(2) paste.
AB  - The addition of various amounts of a strong oxidizing agent (3,5
      dinitrosalicyclic acid, DNSA) to TiO2 paste enhances the solar-to-electrical
      energy conversion efficiency of the corresponding dye-sensitized solar cells
      (DSSCs). Maximum performance was obtained from a device that was fabricated by
      using a TiO2 paste with 2 wt % DNSA, which showed a short-circuit current density
      of 17.88 mA cm(-2) , an open-circuit voltage of 0.78 V, and an overall conversion
      efficiency of 9.62 %, which was an improvement in comparison to reference cells
      without DNSA. This improvement was rationalized in terms of the amount of
      residual carbon (formed due to the oxidation of binders) remaining on the TiO2
      surface. Addition of a larger amount of oxidizing agent led to a smaller amount
      of residual carbon on the TiO2 surface. This smaller amount of residual carbon
      enhanced the adsorption of a larger number of dye molecules on the TiO2 surface.
      The addition of an oxidizing agent facilitated the removal of more residual
      organic species during the high-temperature calcination process while causing no
      change in the surface morphology and microstructure of the TiO2 film. 

PMID- 24106169
TI  - Remembrance of Hugh E. Huxley, a founder of our field.
AB  - Hugh E. Huxley (1924-2013) carried out structural studies by X-ray fiber
      diffraction and electron microscopy that established how muscle contracts.
      Huxley's sliding filament mechanism with an ATPase motor protein taking steps
      along an actin filament, established the paradigm not only for muscle contraction
      but also for other motile systems using actin and unconventional myosins,
      microtubules and dynein and microtubules and kinesin.

PMID- 24106170
TI  - Assessing near infrared optical properties of ceramic orthodontic brackets using
      cross-polarization optical coherence tomography.
AB  - Secondary decay (caries) under ceramic orthodontic brackets remains a significant
      dental problem and near infrared cross-polarization optical coherence tomography
      (CP-OCT) has the potential to detect underlying demineralization. The purpose of
      this study was to determine the effect of crystalline structure and chemical
      composition of ceramic brackets on CP-OCT imaging. Four ceramic brackets types,
      which were divided into monocrystalline and polycrystalline, were examined using
      CP-OCT. The results of this study demonstrated that the crystallinity of the
      ceramic brackets affected the 1310 nm CP-OCT imaging with the greatest
      attenuation seen in polycrystalline alumina brackets. The alumina polycrystalline
      bracket materials had significantly higher attenuation and scattering than
      alumina monocrystalline brackets (p < 0.05, ANOVA, Bonferroni). Additionally,
      bracket base morphology and composition affected NIR light attenuation. There was
      considerable attenuation in bracket bases that contained additive zirconium
      spheres (~30 um) and this alteration was significantly greater than the jagged
      alumina crystallographic alterations found in the other bracket systems (p <
      0.05, ANOVA, Bonferroni). Noninvasive, near infrared (NIR) cross-polarization
      optical coherence tomography (CP-OCT) has potential to effectively image through
      portions of ceramic brackets; however, further investigation into the optical
      effects of resin integration in the base portion of the brackets is warranted.

PMID- 24106171
TI  - A high-yielding CHO transient system: coexpression of genes encoding EBNA-1 and
      GS enhances transient protein expression.
AB  - An efficient rapid protein expression system is crucial to support early drug
      development. Transient gene expression is an effective route, and to facilitate
      the use of the same host cells as for subsequent stable cell line development, we
      have created a high-yielding Chinese hamster ovary (CHO) transient expression
      system. Suspension-adapted CHO-K1 host cells were engineered to express the gene
      encoding Epstein-Barr virus (EBV) nuclear antigen-1 (EBNA-1) with and without the
      coexpression of the gene for glutamine synthetase (GS). Analysis of the
      transfectants indicated that coexpression of EBNA-1 and GS enhanced transient
      expression of a recombinant antibody from a plasmid carrying an OriP DNA element
      compared to EBNA-1-only transfectants. This was confirmed with the retransfection
      of an EBNA-1-only cell line with a GS gene. The retransfected cell lines showed
      an increase in transient expression when compared with that of the EBNA-1-only
      parent. The transient expression process for the best CHO transient cell line was
      further developed to enhance protein expression and improve scalability by
      optimizing the transfection conditions and the cell culture process. This
      resulted in a scalable CHO transient expression system that is capable of
      expressing 2 g/L of recombinant proteins such as antibodies. This system can now
      rapidly provide gram amounts of recombinant antibody to supply preclinical
      development studies that has comparable product quality to antibody produced from
      a stably transfected CHO cell line.

PMID- 24106173
TI  - Distinct trajectories of disease activity over the first year in early rheumatoid
      arthritis patients following a treat-to-target strategy.
AB  - Objective: Although treat-to-target (T2T) strategies are effective in early RA
      patients, important individual variations exist in the course towards remission.
      Growth mixture modeling (GMM) provides more insight into this heterogeneity by
      identifying subgroups of patients with similar response patterns. This study
      aimed to identify distinct trajectories of disease activity in early RA patients
      following a T2T strategy, during their first year. Methods: Data on various
      clinical and patient-reported measures were collected from the DREAM remission
      induction cohort. GMM was applied to examine the impact of T2T on subgroups
      characterized by different types of growth trajectories, as measured with the
      Disease Activity Score for 28 joints. Results: Three distinct trajectories of
      disease activity were found. The normative trajectory contained most patients
      (82.6%), showing a quickly decreasing disease activity, stabilizing at remission
      after 9 months. This group performed best on clinical and patient-reported
      measures over time and were more likely to be men. A smaller group (14.1%) also
      approached remission, but demonstrated a slower response to treatment. Finally, a
      minority (3.3%) showed no improvement after 1 year, despite an initial quick
      decrease in disease activity during the first months of treatment. Conclusion:
      Disease activity in early RA patients during the first year of a T2T strategy
      does not follow a linear pattern, nor is a single developmental trajectory
      applicable to all patients. Future studies should attempt to identify more
      specific risk factors for poor outcome to enable early identification of patients
      in need of alternative therapeutic approaches.

PMID- 24106172
TI  - External validity and reliability of the Psychosocial Assessment Tool (PAT) among
      Canadian parents of children newly diagnosed with cancer.
AB  - BACKGROUND: The Psychosocial Screening Tool (PAT) was developed and validated
      with a sample of caregivers of children newly diagnosed with cancer in the United
      States. This study aimed to assess cultural adaptation (Phase 1) and validity and
      reliability of the revised PAT (PATrev) with a Canadian sample (Phase 2).
      PROCEDURE: In Phase 1, a convenience sample of seven parents of children who were
      treated for cancer and six pediatric oncology healthcare experts participated. In
      Phase 2, 67 parents of children newly diagnosed with cancer from 4 Canadian
      pediatric cancer centers participated. To assess reliability and validity of the
      PATrev, parents completed behavioral (BASC-2) and quality of life (PedsQL)
      instruments about the child and an anxiety inventory (STAI) about themselves.
      RESULTS: The PAT required minor changes to be culturally adapted for the Canadian
      population. The PATrev had strong inter-rater (0.77) test-retest (0.75), and
      internal consistency reliability (0.85), as well as moderate to strong validity
      comparing PATrev child's problems and PedsQL total (-0.49), PedsQL anxiety (
      0.47), BASC-2 internalizing (0.64), behavioral (0.63), and adaptive scores (
      0.56). PATrev discriminative validity was confirmed with BASC-2 scores (AUR
      scores of 0.70-0.74). PATrev parental stressors were strongly correlated to STAI
      scores (0.53). Finally, agreement between PATrev child's problems and parental
      anxiety scores was moderate (0.47). CONCLUSION: This study supports the original
      PAT, demonstrates PATrev is a reliable and valid psychosocial screening tool, and
      provides unique evidence regarding early psychosocial risk in the family, which
      have important implications for guiding psychosocial practice.

PMID- 24106174
TI  - Measurement by SPR of very low dissociation rates: oxidation-mediated loss of
      biotin-streptavidin affinity.
AB  - Long-term relationship: biotin labels on RNAs, and possibly other
      biomacromolecules, are easily oxidized causing a dramatic loss of affinity for
      streptavidin and adversely affecting the measurement of high-affinity
      interactions. A new SPR method has been developed for measuring the very low rate
      dissociation constants of biotin- and biotin oxide-conjugated RNAs with
      streptavidin.

PMID- 24106175
TI  - Evaluation of protein extraction protocols for 2DE in marine ecotoxicoproteomics.
AB  - In ecotoxicoproteomics, an accurate and reproducible extraction of proteins is a
      critical step for 2DE analysis and further protein identification using MS. The
      criteria for the assessment of protein extraction quality include protein yield,
      protein spots resolved in a 2DE gel, matched protein spots in replicate gels,
      reproducibility, and compatibility with MS. In this work, we evaluated three
      protein extraction systems, straightforward lysis buffer, trichloroacetic acid
      acetone, and TRIzol reagent with some modifications, for the protein extraction
      from three animal species including mussel Mytilus galloprovincialis, flounder
      Paralichthys olivaceus, and polychaete Nereis diversicolor used in marine
      ecotoxicology. Our results indicated that these methods could extract
      significantly different protein profiles. The method using TRIzol reagent
      resulted in the most matched protein spots resolved in four replicate 2DE gels
      and highest reproducibilities for the gill of M. galloprovincialis and liver of
      P. olivaceus. However, a modified trichloroacetic acid-acetone solvent system was
      best for the whole soft tissue of N. diversicolor. This work provides the
      fundamental information of the extraction quality of protein extraction protocols
      from different marine animals, which may facilitate the selection of a suitable
      protein extraction protocol for ecotoxicoproteomics. 

PMID- 24106176
TI  - Exosome encased spherical nucleic acid gold nanoparticle conjugates as potent
      microRNA regulation agents.
AB  - Exosomes are a class of naturally occurring nanomaterials that play crucial roles
      in the protection and transport of endogenous macromolecules, such as microRNA
      and mRNA, over long distances. Intense effort is underway to exploit the use of
      exosomes to deliver synthetic therapeutics. Herein, transmission electron
      microscopy is used to show that when spherical nucleic acid (SNA) constructs are
      endocytosed into PC-3 prostate cancer cells, a small fraction of them (<1%) can
      be naturally sorted into exosomes. The exosome-encased SNAs are secreted into the
      extracellular environment from which they can be isolated and selectively re
      introduced into the cell type from which they were derived. In the context of
      anti-miR21 experiments, the exosome-encased SNAs knockdown miR-21 target by
      approximately 50%. Similar knockdown of miR-21 by free SNAs requires a ~3000-fold
      higher concentration. 

PMID- 24106177
TI  - Impaired decline in renal threshold for glucose during pregnancy - a possible
      novel mechanism for gestational diabetes mellitus.
AB  - BACKGROUND: The renal threshold for glucose (RT(G)) is determined by the
      nephron's reabsorptive capacity. Glucose is reabsorbed through sodium-coupled
      glucose cotransporters in the proximal tubules. During pregnancy, renal glucose
      reabsorptive capacity decreases, possibly, due to reduced glucose transporter
      expression. Our hypothesis is that inadequate decrease in RT(G) during pregnancy
      will make women more prone to develop gestational diabetes mellitus (GDM).
      METHODS: Pregnant women (n = 40) who were referred to our center for oral glucose
      tolerance test (OGTT) were included in the analysis. Plasma glucose levels and
      urinary glucose excretion were measured for 4 h after 100 g oral glucose load.
      These data were used to calculate RT(G) . The subjects were divided into two
      cohorts, GDM and non-GDM, according to the OGTT results. Mean RT(G) was compared
      between the two groups. RESULTS: Fifteen (37.5%) of the women were diagnosed with
      GDM. Seventeen participants had only trace amounts of urinary glucose excretion,
      and no value of RT(G) could be determined; RT(G) was determined in the other 23
      subjects. Among these 23 women, 13 were diagnosed as GDM, and 10 had normal OGTT.
      RT(G) was lower in the non-GDM women (146 +/- 14 mg/dL) than in the GDM women
      (182 +/- 18 mg/dL), p < 0.001. CONCLUSIONS: Gestational diabetes mellitus is
      associated with higher RT(G) during pregnancy compared with non-GDM. These
      results support our hypothesis that inadequate decrease of the RT(G) may have a
      pathophysiological role in the development of GDM.

PMID- 24106178
TI  - Comparison of homogeneous and heterogeneous catalysts for glucose-to-fructose
      isomerization in aqueous media.
AB  - Herein, the first comparison of the mechanisms of glucose-to-fructose
      isomerization in aqueous media enabled by homogeneous (CrCl3 and AlCl3 ) and
      heterogeneous catalysts (Sn-beta) by using isotopic-labeling studies is reported.
      A pronounced kinetic isotope effect (KIE) was observed if the deuterium label was
      at the C2 position, thus suggesting that a hydrogen shift from the C2 to C1
      positions was the rate-limiting step with the three catalysts. (13) C and (1) H
      NMR spectroscopic investigations confirmed that an intra-hydride-transfer
      reaction pathway was the predominant reaction channel for all three catalysts in
      aqueous media. Furthermore, the deuterium atom in the labeled glucose could be
      mapped onto hydroxymethylfurfural and formic acid through reactions that followed
      the isomerization step in the presence of Bronsted acids. In all three catalysts,
      the active site appeared to be a bifunctional Lewis-acidic/Bronsted-basic site,
      based on a speciation model and first-principles calculations. For the first
      time, a mechanistic similarities between the homogeneous and heterogeneous
      catalysis of aldose-to-ketose isomerization is established and it is suggested
      that learning from homogeneous catalysis could assist in the development of
      improved heterogeneous catalysts. 

PMID- 24106180
TI  - A qualitative study of Egyptian school nurses' attitudes and experiences toward
      sex and relationship education.
AB  - School nurses play a vital role in the promotion of sexual health. However, there
      is very limited evidence of how school nurses experience this topic in an Islamic
      cultural setting. Using an exploratory qualitative design, 13 in-depth interviews
      were conducted with Egyptian school nurses. Data were subject to thematic
      analysis. Four themes emerged from this analysis, "personal issues," "cultural
      and political dimensions," "parental issues," and "skills and confidence." These
      themes represented how nurses' views on sex education were tempered by personal
      and social forces--affecting their practice. Fear of being blamed for creating a
      permissive culture was a feature of nurses' concerns in this culture. The belief
      that sex education is morally challenging affected nurses and must be addressed
      to enable effective sex education to take place. School nurses must contribute
      actively to this debate and receive governmental support.

PMID- 24106179
TI  - COX-(2) overexpression in sinonasal inverted papilloma.
AB  - BACKGROUND: Inverted papilloma (IP) is a benign, but locally aggressive neoplasm
      of the nasal cavity and paranasal sinuses. The mainstay of treatment of IP is
      surgical resection, but high rates of tumor recurrence have been reported. Cyclo
      oxygenase-2 (COX-2) has been found to be overexpressed in many tumors and has
      been used successfully as a therapeutic target. The goal of this study is to
      highlight COX-2 expression in IP. METHODS: Immunohistochemistry for COX-2 was
      performed on IP samples obtained during surgical resection between January 2012
      and June 2013. The intensity of staining was evaluated by 2 head and neck
      pathologists blinded to the clinical features and outcomes. A positive stain was
      defined as having 10% or more of tumor cells exhibiting immunoreactivity.
      RESULTS: The study includes 13 tumor samples from 7 females and 6 males. Mean age
      was 54.5 (range, 18-81) years. Tumor locations included: nasal septum (1),
      ethmoid (3), sphenoid (4), and maxillary (5) sinuses. No tumors demonstrated
      malignancy or dysplasia. Five (38%) of the 13 IP samples stained strongly
      positive for COX-2, and 3 of 13 (23%) stained weakly positive. There were no
      clinical differences in patients that stained strongly or weakly for COX-2.
      CONCLUSION: COX-2 overexpression was identified in 62% of cases of IP in this
      study, and strongly positive in 38% of cases. Larger studies are necessary to
      identify the true incidence of COX-2 expression for this tumor. Pharmaceuticals
      targeting COX-2 may eventually provide an additional therapeutic option for
      select cases of recurrent or unresectable IP.

PMID- 24106181
TI  - Identification, characterization, and expression of dentin matrix protein 1 gene
      in Xenopus laevis.
AB  - Dentin matrix protein 1 (DMP1) is an acidic extracellular matrix protein
      expressed mainly in bone and dentin, and is a member of the small integrin
      binding ligand N-linked glycoprotein (SIBLING) family. The DMP1 gene, however,
      appears to evolve rapidly in comparison with other SIBLING genes, even though
      such functionally important molecules usually evolve more slowly than less
      important ones. The purpose of this study was to identify and characterize an
      ortholog of the DMP1 gene in an amphibian (Xenopus laevis; X. laevis) to clarify
      molecular evolutionary alterations in DMP1 associated with calcified tissues in
      tetrapods. Furthermore, we analyzed the mRNA expression of this gene to elucidate
      its functional change in bone and developing tooth germ in comparison with
      amniote DMP1s. The similarities of the deduced amino acid sequence of X. laevis
      DMP1 to that of the corresponding amniote proteins were low, although they did
      share several unique features specific to DMP1 and have similar properties.
      Expression of X. laevis DMP1 mRNA was predominant in osteocytes and odontoblasts,
      but only transiently observed in ameloblasts, as in amniotes. These results
      suggest that DMP1 has conserved several functions during tetrapod evolution. This
      indicates that continuity of biochemical properties has been more important in
      maintaining DMP1 functionality than that of the sequence of amino acid residues,
      which has undergone change over the course of molecular evolution.

PMID- 24106182
TI  - Antioxidant efficacy and adhesion rescue by a recombinant mussel foot protein-6.
AB  - Mytilus foot protein type 6 (mfp-6) is crucial for maintaining the reducing
      conditions needed for optimal wet adhesion in marine mussels. In this report, we
      describe the expression and production of a recombinant Mytilus californianus
      foot protein type 6 variant 1 (rmfp-6.1) fused with a hexahistidine affinity tag
      in Escherichia coli and its purification by affinity chromatography. Recombinant
      mfp-6 showed high purification yields of 5-6 mg L(-1) cell culture and excellent
      solubility in low pH buffers that retard oxidation of its many thiol groups.
      Purified rmfp-6.1 protein showed high 2,2-diphenyl-1-picrylhydrazyl radical
      scavenging activity when compared with vitamin C. Using the highly sensitive
      surface forces apparatus (SFA) technique to measure interfacial surface forces in
      the nano-Newton range, we show that rmfp-6.1 is also able to rescue the oxidation
      dependent adhesion loss of mussel foot protein 3 (mfp-3) at pH 3. The adhesion
      rescue is related to a reduction of dopaquinone back to 3,4-dihydroxyphenyl-l
      alanine in mfp-3, which is the reverse reaction observed during the detrimental
      enzymatic browning process in fruits and vegetables. Broadly viewed, rmfp-6.1 has
      potential as a versatile antioxidant for applications ranging from personal
      products to antispoilants for perishable foods during processing and storage. (c)
      2013 American Institute of Chemical Engineers Biotechnol. Prog., 29:1587-1593,
      2013.

PMID- 24106184
TI  - Capillaria hepatica pseudoinfection.

PMID- 24106183
TI  - Estimating the occurrence of renal complications among persons with ankylosing
      spondylitis.
AB  - OBJECTIVE: The few published estimates of the risk of renal complications in
      ankylosing spondylitis (AS) are established on clinic-based studies. Our
      objective was to estimate the age- and sex-specific risks of renal complications
      in a population-based cohort of AS subjects in Quebec between 1996 and 2006,
      relative to the general population. METHODS: A retrospective cohort design was
      implemented using population-based administrative data collected from 1996 to
      2006 in Quebec, Canada. The study cohort included subjects diagnosed with AS on
      physician billing records, and the comparison cohort comprised a 1% random sample
      of subjects without AS. Age- and sex-stratified prevalence ratios for acute
      kidney injury, chronic kidney disease, amyloidosis, and hypertensive renal
      disease were compared between subjects with and without AS. RESULTS: The AS
      cohort included 4,836 men and 3,780 women. Renal complications were diagnosed
      among 3.4% of men and 2.1% of women with AS compared with 2.0% and 1.6% of
      persons without AS, respectively. Renal complications were 72% more prevalent
      among persons with AS and an increase was observed in each of the conditions. The
      magnitude of the risk of renal complications was highest among younger
      individuals and decreased with advancing age. CONCLUSION: These findings indicate
      that renal complications may be elevated among persons with AS, especially at
      younger ages. Despite the limitations of administrative data pertaining to onset
      of disease, these findings warrant further investigation because of their
      clinical relevance.

PMID- 24106185
TI  - Eyes on the prize: lessons from the cholera wars for modern scientists,
      physicians, and public health officials.

PMID- 24106186
TI  - Cholera elimination in Hispaniola.

PMID- 24106187
TI  - Use of oral cholera vaccine in Haiti: a rural demonstration project.
AB  - A cholera epidemic has claimed the lives of more than 8,000 Haitians and sickened
      650,000 since the outbreak began in October 2010. Early intervention in the
      epidemic focused on case-finding, treatment, and water and sanitation
      interventions for prevention of transmission. Use of oral cholera vaccine (OCV)
      as part of a complementary set of control activities was considered but initially
      rejected by policymakers. In December 2011, the Minister of Health of Haiti
      called for a demonstration of the acceptability and feasibility of the use of OCV
      in urban and rural Haiti. This paper describes the collaborative activity that
      offered OCV to one region of the Artibonite Department of rural Haiti in addition
      to other ongoing treatment and control measures. Despite logistics and cold chain
      challenges, 45,417 persons were successfully vaccinated with OCV in the region,
      and 90.8% of these persons completed their second dose.

PMID- 24106188
TI  - Predictors of disease severity in patients admitted to a cholera treatment center
      in urban Haiti.
AB  - Cholera, previously unrecognized in Haiti, spread through the country in the fall
      of 2010. An analysis was performed to understand the epidemiological
      characteristics, clinical management, and risk factors for disease severity in a
      population seen at the GHESKIO Cholera Treatment Center in Port-au-Prince. A
      comprehensive review of the medical records of patients admitted during the
      period of October 28, 2010-July 10, 2011 was conducted. Disease severity on
      admission was directly correlated with older age, more prolonged length of stay,
      and presentation during the two epidemic waves seen in the observation period.
      Although there was a high seroprevalence of human immunodeficiency virus (HIV),
      severity of cholera was not greater with HIV infection. This study documents the
      correlation of cholera waves with rainfall and its reduction in settings with
      improved sanitary conditions and potable water when newly introduced cholera
      affects all ages equally so that interventions must be directed throughout the
      population.

PMID- 24106189
TI  - Modeling the effect of water, sanitation, and hygiene and oral cholera vaccine
      implementation in Haiti.
AB  - In 2010, toxigenic Vibrio cholerae was newly introduced to Haiti. Because
      resources are limited, decision-makers need to understand the effect of different
      preventive interventions. We built a static model to estimate the potential
      number of cholera cases averted through improvements in coverage in water,
      sanitation and hygiene (WASH) (i.e., latrines, point-of-use chlorination, and
      piped water), oral cholera vaccine (OCV), or a combination of both. We allowed
      indirect effects and non-linear relationships between effect and population
      coverage. Because there are limited incidence data for endemic cholera in Haiti,
      we estimated the incidence of cholera over 20 years in Haiti by using data from
      Malawi. Over the next two decades, scalable WASH interventions could avert 57,949
      78,567 cholera cases, OCV could avert 38,569-77,636 cases, and interventions that
      combined WASH and OCV could avert 71,586-88,974 cases. Rate of implementation is
      the most influential variable, and combined approaches maximized the effect.

PMID- 24106190
TI  - Laboratory-confirmed cholera and rotavirus among patients with acute diarrhea in
      four hospitals in Haiti, 2012-2013.
AB  - An outbreak of cholera began in Haiti in October of 2010. To understand the
      progression of epidemic cholera in Haiti, in April of 2012, we initiated
      laboratory-enhanced surveillance for diarrheal disease in four Haitian hospitals
      in three departments. At each site, we sampled up to 10 hospitalized patients
      each week with acute watery diarrhea. We tested 1,616 specimens collected from
      April 2, 2012 to March 28, 2013; 1,030 (63.7%) specimens yielded Vibrio cholerae,
      13 (0.8%) specimens yielded Shigella, 6 (0.4%) specimens yielded Salmonella, and
      63 (3.9%) specimens tested positive for rotavirus. Additionally, 13.5% of
      children < 5 years old tested positive for rotavirus. Of 1,030 V. cholerae
      isolates, 1,020 (99.0%) isolates were serotype Ogawa, 9 (0.9%) isolates were
      serotype Inaba, and 1 isolate was non-toxigenic V. cholerae O139. During 1 year
      of surveillance, toxigenic cholera continued to be the main cause of acute
      diarrhea in hospitalized patients, and rotavirus was an important cause of
      diarrhea-related hospitalizations in children.

PMID- 24106191
TI  - Access to safe water in rural Artibonite, Haiti 16 months after the onset of the
      cholera epidemic.
AB  - Haiti has the lowest improved water and sanitation coverage in the Western
      Hemisphere and is suffering from the largest cholera epidemic on record. In May
      of 2012, an assessment was conducted in rural areas of the Artibonite Department
      to describe the type and quality of water sources and determine knowledge,
      access, and use of household water treatment products to inform future programs.
      It was conducted after emergency response was scaled back but before longer-term
      water, sanitation, and hygiene activities were initiated. The household survey
      and source water quality analysis documented low access to safe water, with only
      42.3% of households using an improved drinking water source. One-half (50.9%) of
      the improved water sources tested positive for Escherichia coli. Of households
      with water to test, 12.7% had positive chlorine residual. The assessment
      reinforces the identified need for major investments in safe water and sanitation
      infrastructure and the importance of household water treatment to improve access
      to safe water in the near term.

PMID- 24106192
TI  - Seroepidemiologic survey of epidemic cholera in Haiti to assess spectrum of
      illness and risk factors for severe disease.
AB  - To assess the spectrum of illness from toxigenic Vibrio cholerae O1 and risk
      factors for severe cholera in Haiti, we conducted a cross-sectional survey in a
      rural commune with more than 21,000 residents. During March 22-April 6, 2011, we
      interviewed 2,622 residents >= 2 years of age and tested serum specimens from
      2,527 (96%) participants for vibriocidal and antibodies against cholera toxin;
      18% of participants reported a cholera diagnosis, 39% had vibriocidal titers >=
      320, and 64% had vibriocidal titers >= 80, suggesting widespread infection. Among
      seropositive participants (vibriocidal titers >= 320), 74.5% reported no diarrhea
      and 9.0% had severe cholera (reported receiving intravenous fluids and overnight
      hospitalization). This high burden of severe cholera is likely explained by the
      lack of pre-existing immunity in this population, although the virulence of the
      atypical El Tor strain causing the epidemic and other factors might also play a
      role.

PMID- 24106193
TI  - Water, sanitation and hygiene in Haiti: past, present, and future.
AB  - Haiti has the lowest rates of access to improved water and sanitation
      infrastructure in the western hemisphere. This situation was likely exacerbated
      by the earthquake in 2010 and also contributed to the rapid spread of the cholera
      epidemic that started later that same year. This report examines the history of
      the water, sanitation, and hygiene (WASH) sector in Haiti, considering some
      factors that have influenced WASH conditions in the country. We then discuss the
      situation sine the earthquake and subsequent cholera epidemic, and the responses
      to those events. Finally, drawing on Haiti's National Plan of Action for the
      Elimination of Cholera in Haiti 2013-2022, we suggest some actions that could
      help bring about long-term WASH improvements for the future. Because the current
      WASH situation has evolved over decades of limited attention and resources, it
      will take a long-term, sustained effort to improve the situation.

PMID- 24106194
TI  - Cholera vaccination in urban Haiti.
AB  - Successful and sustained efforts have been made to curtail the major cholera
      epidemic that occurred in Haiti in 2010 with the promotion of hygiene and
      sanitation measures, training of health personnel and establishment of treatment
      centers nationwide. Oral cholera vaccine (OCV) was introduced by the Haitian
      Ministry of Health as a pilot project in urban and rural areas. This paper
      reports the successful OCV pilot project led by GHESKIO Centers in the urban
      slums of Port-au-Prince where 52,357 persons received dose 1 and 90.8% received
      dose 2; estimated coverage of the at-risk community was 75%. This pilot study
      demonstrated the effort, community mobilization, and organizational capacity
      necessary to achieve these results in a challenging setting. The OCV intervention
      paved the way for the recent launching of a national cholera vaccination program
      integrated in a long-term ambitious and comprehensive plan to address Haiti's
      critical need in water security and sanitation.

PMID- 24106195
TI  - Development of a cholera vaccination policy on the Island of Hispaniola, 2010
      2013.
AB  - Deployment of oral cholera vaccine (OCV) on the Island of Hispaniola has been
      considered since the emergence of the disease in October of 2010. At that time,
      emergency response focused on the time-tested measures of treatment to prevent
      deaths and sanitation to diminish transmission. Use of the limited amount of
      vaccine available in the global market was recommended for demonstration
      activities, which were carried out in 2012. As transmission continues,
      vaccination was recommended in Haiti as one component of a comprehensive
      initiative supported by an international coalition to eliminate cholera on the
      Island of Hispaniola. Leveraging its delivery to strengthen other cholera
      prevention measures and immunization services, a phased OCV introduction is
      pursued in accordance with global vaccine supply. Not mutually exclusive or
      sequential deployment options include routine immunization for children over the
      age of 1 year and campaigns in vulnerable metropolitan areas or rural areas with
      limited access to health services.

PMID- 24106196
TI  - Implementation of an alert and response system in Haiti during the early stage of
      the response to the cholera epidemic.
AB  - The start of the cholera epidemic in Haiti quickly highlighted the necessity of
      the implementation of an Alert and Response (A&R) System to complement the
      existing national surveillance system. The national system had been able to
      detect and confirm the outbreak etiology but required external support to monitor
      the spread of cholera and coordinate response, because much of the information
      produced was insufficiently timely for real-time monitoring and directing of a
      rapid, targeted response. The A&R System was designed by the Pan American Health
      Organization/World Health Organization in collaboration with the Haiti Ministry
      of Health, and it was based on a network of partners, including any institution,
      structure, or individual that could identify, verify, and respond to alerts. The
      defined objectives were to (1) save lives through early detection and treatment
      of cases and (2) control the spread through early intervention at the community
      level. The operational structure could be broken down into three principle
      categories: (1) alert (early warning), (2) verification and assessment of the
      information, and (3) efficient and timely response in coordination with partners
      to avoid duplication. Information generated by the A&R System was analyzed and
      interpreted, and the qualitative information was critical in qualifying the
      epidemic and defining vulnerable areas, particularly because the national
      surveillance system reported incomplete data for more than one department. The
      A&R System detected a number of alerts unrelated to cholera and facilitated rapid
      access to that information. The sensitivity of the system and its ability to
      react quickly was shown in May of 2011, when an abnormal increase in alerts
      coming from several communes in the Sud-Est Department in epidemiological weeks
      (EWs) 17 and 18 were noted and disseminated network-wide and response activities
      were implemented. The national cholera surveillance system did not register the
      increase until EWs 21 and 22, and the information did not become available until
      EWs 23 and 24, when the peak of cases had already been reached. Although many of
      the partners reporting alerts during the peak of the cholera epidemic have since
      left Haiti, the A&R System has continued to function as an Early Warning (EWARN)
      System, and it continues to be developed with recent activities, such as the
      distribution of cell phones to enhance alert communication.

PMID- 24106197
TI  - Surface proteomic analysis of differentiated versus stem-like osteosarcoma human
      cells.
AB  - Cancer stem cell characterization represents a breakthrough in cancer research.
      Despite evidence showing the existence and the role of cancer stem cells in
      osteosarcoma (OS) onset and progression, little is known about their specific
      surface phenotype. To address this issue, we carried out a cytometric analysis
      with an antibody-array comprising 245 membrane proteins comparing the stem and
      differentiated OS cells. As experimental model, we chose the stem-like cell line
      3aminobenzamide-OS and its parental, differentiated, cell line MG63. We
      identified 50 differentially expressed, 23 homogeneously expressed, and 172 not
      expressed proteins in the two cell line models, thus defining a surface protein
      signature specific for each of them. Furthermore, we selected ERK1/2 (p44/42
      mitogen-activated protein kinases) as a potential pathway correlated with
      processes that characterize tumorigenic potential and stemness of 3aminobenzamide
      OS cells. 

PMID- 24106198
TI  - Deoxyribozyme cascade for visual detection of bacterial RNA.
AB  - In the blink of the eye: a cascade of two deoxyribozymes was designed for rapid
      visual detection of bacterial 16S rRNA. The detection limit is 12.5 ng by the
      naked eye, with the ability to differentiate between closely related pathogenic
      and nonpathogenic species.

PMID- 24106199
TI  - Striking hematological abnormalities in patients with microcephalic
      osteodysplastic primordial dwarfism type II (MOPD II): a potential role of
      pericentrin in hematopoiesis.
AB  - BACKGROUND: Microcephalic osteodysplastic primordial dwarfism type II (MOPD II)
      is a rare primordial dwarfism that is similar to Seckel syndrome. Seckel syndrome
      is known to be associated with various hematological abnormalities; however,
      hematological findings in MOPD II patients have not been previously reported. The
      present study aimed to describe the hematological findings in a series of eight
      patients with MOPD II from a single center. MATERIALS AND METHODS: The study
      included eight patients with MOPD II that were analyzed via molecular testing,
      and physical and laboratory examinations. RESULTS: Molecular testing showed that
      seven of the eight patients had pericentrin (PCNT) gene mutations. Hematological
      evaluation showed that 7 (87.5%) patients had thrombocytosis, 6 (75%) had
      leukocytosis, 5 (62.5%) had both leukocytosis and thrombocytosis, and 2 (25%) had
      anemia. CONCLUSIONS: We report leukocytosis and thrombocytosis as a common
      hematologic abnormality in patients with MOPD II. The present findings may
      improve our understanding of the potential function of the PCNT gene in
      hematopoietic cell proliferation and differentiation.

PMID- 24106200
TI  - Periodic AuAg-Ag2S heterostructured nanowires.

PMID- 24106201
TI  - Crystal-plane-controlled surface chemistry and catalytic performance of
      surfactant-free Cu2 O nanocrystals.
AB  - Surfactant-free Cu2 O nanocrystals, including cubes exposing {100} crystal
      planes, octahedra exposing {111} crystal planes, and rhombic dodecahedra exposing
      {110} crystal planes, were used as model catalysts to study the effect of the
      crystal plane on the surface chemistry and catalytic performance for CO oxidation
      of Cu2 O nanocrystals. The catalytic performance follows the order of octahedra
      rhombic dodecahedra>cubes; this suggests that Cu2 O(111) is most active in
      catalyzing CO oxidation among Cu2 O (111), (110), and (100) surfaces. CO
      temperature-programmed reduction results demonstrate that Cu2 O octahedra are the
      most easily reduced of the Cu2 O cubes, octahedra, and rhombic dodecahedra.
      Diffuse reflectance FTIR spectra show that CO chemisorption on Cu2 O nanocrystals
      depends on their shape and the chemisorption temperature. CO chemisorption is
      strongest on rhombic dodecahedra at 30 degrees C, but at 150 degrees C on
      octahedra. Both the reducibility and chemisorption ability of various Cu2 O
      nanocrystals toward CO are consistent with their catalytic performance in CO
      oxidation. The observed surface chemistry and catalytic performance in CO
      oxidation of various Cu2 O nanocrystals can be well correlated with their exposed
      crystal plane and surface composition/structure. Cu2 O octahedra expose the {111}
      crystal plane with coordinated, unsaturated Cu(I) sites, and thus, are most
      active in chemisorbing CO and catalyzing CO oxidation. These results nicely
      demonstrate the crystal-plane-controlled surface chemistry and catalytic
      performance of oxide catalysts.

PMID- 24106203
TI  - Taste and odorant receptors of the coelacanth--a gene repertoire in transition.
AB  - G-protein coupled chemosensory receptors (GPCR-CRs) aid in the perception of
      odors and tastes in vertebrates. So far, six GPCR-CR families have been
      identified that are conserved in most vertebrate species. Phylogenetic analyses
      indicate differing evolutionary dynamics between teleost fish and tetrapods. The
      coelacanth Latimeria chalumnae belongs to the lobe-finned fishes, which represent
      a phylogenetic link between these two groups. We searched the genome of L.
      chalumnae for GPCR-CRs and found that coelacanth taste receptors are more similar
      to those in tetrapods than in teleost fish: two coelacanth T1R2s co-segregate
      with the tetrapod T1R2s that recognize sweet substances, and our phylogenetic
      analyses indicate that the teleost T1R2s are closer related to T1R1s (umami taste
      receptors) than to tetrapod T1R2s. Furthermore, coelacanths are the first fish
      with a large repertoire of bitter taste receptors (58 T2Rs). Considering current
      knowledge on feeding habits of coelacanths the question arises if perception of
      bitter taste is the only function of these receptors. Similar to teleost fish,
      coelacanths have a variety of olfactory receptors (ORs) necessary for perception
      of water-soluble substances. However, they also have seven genes in the two
      tetrapod OR subfamilies predicted to recognize airborne molecules. The two
      coelacanth vomeronasal receptor families are larger than those in teleost fish,
      and similar to tetrapods and form V1R and V2R monophyletic clades. This may point
      to an advanced development of the vomeronasal organ as reported for lungfish. Our
      results show that the intermediate position of Latimeria in the phylogeny is
      reflected in its GPCR-CR repertoire.

PMID- 24106202
TI  - Three-dimensional volumetric computed tomographic scoring as an objective outcome
      measure for chronic rhinosinusitis: clinical correlations and comparison to Lund
      Mackay scoring.
AB  - BACKGROUND: We aimed to test the hypothesis that three-dimensional (3D) volume
      based scoring of computed tomography (CT) images of the paranasal sinuses was
      superior to Lund-Mackay CT scoring of disease severity in chronic rhinosinusitis
      (CRS). We determined correlation between changes in CT scores (using each scoring
      system) with changes in other measures of disease severity (symptoms, endoscopic
      scoring, and quality of life) in patients with CRS treated with triamcinolone.
      METHODS: The study group comprised 48 adult subjects with CRS. Baseline symptoms
      and quality of life were assessed. Endoscopy and CT scans were performed.
      Patients received a single systemic dose of intramuscular triamcinolone and were
      reevaluated 1 month later. Strengths of the correlations between changes in CT
      scores and changes in CRS signs and symptoms and quality of life were determined.
      RESULTS: We observed some variability in degree of improvement for the different
      symptom, endoscopic, and quality-of-life parameters after treatment. Improvement
      of parameters was significantly correlated with improvement in CT disease score
      using both CT scoring methods. However, volumetric CT scoring had greater
      correlation with these parameters than Lund-Mackay scoring. CONCLUSION:
      Volumetric scoring exhibited higher degree of correlation than Lund-Mackay
      scoring when comparing improvement in CT score with improvement in score for
      symptoms, endoscopic exam, and quality of life in this group of patients who
      received beneficial medical treatment for CRS.

PMID- 24106204
TI  - Imaging of the temporomandibular joint in juvenile idiopathic arthritis.
AB  - OBJECTIVE: Temporomandibular joint (TMJ) arthritis in children with juvenile
      idiopathic arthritis (JIA) is extremely common but frequently asymptomatic.
      Magnetic resonance imaging (MRI) with contrast remains the gold standard for
      identifying TMJ arthritis in JIA. A reliable scoring system with published MRI
      examples of typical acute and chronic TMJ arthritis changes will be invaluable
      for future prospective treatment trials of TMJ arthritis in JIA. METHODS: MRIs
      were collected from routine clinical studies assessing TMJ arthritis in JIA.
      Representative images were selected for publication to depict acute (synovial
      fluid, bone marrow edema, and synovial enhancement) and chronic (pannus, disc
      derangement, and condylar head flattening and erosions) TMJ arthritis findings. A
      preliminary MRI-based scoring system for assessing degrees of acute and chronic
      TMJ arthritis was developed and tested for inter- and intrareader reliability.
      RESULTS: TMJ MRIs representative of acute and chronic TMJ arthritis in JIA were
      selected from among thousands taken (>500 TMJ MRI studies annually at Children's
      of Alabama) since September 2007. Moreover, computed tomography scans depicting
      select bony changes (osteophyte formation, micrognathia) were chosen for
      publication. A description of the MRI protocol for assessing TMJ arthritis is
      included. A preliminary scoring system weighted for degree of acute and chronic
      TMJ arthritis MRI findings was found to have substantial inter- and intrareader
      reliability. CONCLUSION: A published set of MRIs depicting representative acute
      and chronic changes will help establish a standardized scoring system to assess
      TMJ arthritis in children with JIA. Future validation will aid in assessing
      improvement during treatment trials of TMJ arthritis.

PMID- 24106205
TI  - Altered glycosylation of platelet-derived von Willebrand factor confers
      resistance to ADAMTS13 proteolysis.
AB  - Platelet-von Willebrand factor (VWF) is stored within alpha-granules and accounts
      for ~20% of total VWF in platelet-rich plasma. This platelet-VWF pool is distinct
      from plasma-VWF and is enriched in high molecular weight multimers (HMWM).
      Previous studies have described significant functional discrepancies between
      platelet-VWF and plasma-VWF; however, the molecular basis of these differences is
      not well understood. We have characterized terminal glycan expression on platelet
      VWF. Our findings demonstrate that platelet-VWF exists as a distinct natural
      glycoform. In particular, N-linked sialylation is markedly reduced (>50%)
      compared with plasma-VWF. Moreover, unlike plasma-VWF, platelet-VWF does not
      express AB blood group determinants, although precursor H antigen expression is
      similar to that on plasma-VWF. Because of this differential glycosylation,
      platelet-VWF exhibits specific resistance to ADAMTS13 proteolysis. Thus platelet
      activation at sites of vascular injury results in the release of high local
      concentrations of HMWM platelet-VWF that is more resistant to ADAMTS13, thereby
      facilitating platelet-plug formation. 

PMID- 24106206
TI  - Coordinated and unique functions of the E-selectin ligand ESL-1 during
      inflammatory and hematopoietic recruitment in mice.
AB  - Beyond its well-established roles in mediating leukocyte rolling, E-selectin is
      emerging as a multifunctional receptor capable of inducing integrin activation in
      neutrophils, and of regulating various biological processes in hematopoietic
      precursors. Although these effects suggest important homeostatic contributions of
      this selectin in the immune and hematologic systems, the ligands responsible for
      transducing these effects in different leukocyte lineages are not well defined.
      We have characterized mice deficient in E-selectin ligand-1 (ESL-1), or in both P
      selectin glycoprotein-1 (PSGL-1) and ESL-1, to explore and compare the
      contributions of these glycoproteins in immune and hematopoietic cell
      trafficking. In the steady state, ESL-1 deficiency resulted in a moderate myeloid
      expansion that became more prominent when both glycoproteins were eliminated.
      During inflammation, PSGL-1 dominated E-selectin binding, rolling, integrin
      activation, and extravasation of mature neutrophils, but only the combined
      deficiency in PSGL-1 and ESL-1 completely abrogated leukocyte recruitment.
      Surprisingly, we find that the levels of ESL-1 were strongly elevated in
      hematopoietic progenitor cells. These elevations correlated with a prominent
      function of ESL-1 for E-selectin binding and for migration of hematopoietic
      progenitor cells into the bone marrow. Our results uncover dominant roles for ESL
      1 in the immature compartment, and a functional shift toward PSGL-1 dependence in
      mature neutrophils. 

PMID- 24106207
TI  - Glycoengineered CD20 antibody obinutuzumab activates neutrophils and mediates
      phagocytosis through CD16B more efficiently than rituximab.
AB  - Obinutuzumab (GA101) is a glycoengineered type 2 CD20 antibody with enhanced
      CD16A-binding and natural killer-mediated cytotoxicity. CD16B is highly
      homologous to CD16A and a major FcgammaR on human polymorphonuclear neutrophils
      (PMNs). We show here that glycoengineered obinutuzumab or rituximab bound CD16B
      with approximately sevenfold higher affinity, compared with nonglycoengineered
      wild-type parental antibodies. Furthermore, glycoengineered obinutuzumab
      activated PMNs, either purified or in chronic lymphoblastic leukemia whole blood,
      more efficiently than wild-type rituximab. Activation resulted in a 50% increase
      in CD11b expression and 70% down-modulation of CD62L on neutrophils and in
      release of tumor necrosis factor alpha, IL-6, and IL-8. Activation was not
      accompanied by generation of reactive oxygen species or antibody-dependent
      cellular cytotoxicity activity, but led to up to 47% phagocytosis of
      glycoengineered anti-CD20 opsonized chronic lymphoblastic leukemia targets by
      purified PMNs. Significant phagocytosis was observed in whole blood, but only in
      the presence of glycoengineered antibodies, and was followed by up to 50% PMN
      death. Finally we show, using anti-CD16B and anti-CD32A Fab and F(ab')2
      fragments, that both of these receptors are involved in PMN activation,
      phagocytosis, and cell death induced by glycoengineered antibodies. We conclude
      that phagocytosis by PMNs is an additional mechanism of action of obinutuzumab
      mediated through its higher binding affinity for CD16B. 

PMID- 24106208
TI  - Amino-functionalized macroporous silica for efficient tryptic digestion in acidic
      solutions.
AB  - Amino-functionalized macroporous silica foam (NH2 -MOSF) has been developed as a
      host reactor to realize highly efficient proteolysis in acidic solutions where
      normal tryptic reactions cannot occur. The digestion protocol consists simply of
      adding the functionalized NH2 -MOSF into the protein and trypsin solutions
      without altering the bulk pH or preloading the enzymes on the materials. With
      this protocol, digestion of sample fractions from LC can be efficiently realized
      in the acidic solutions directly. Digestion of a protein fraction extracted from
      rat liver tissue after LC separation was performed to illustrate this principle,
      where 103 proteins were successfully identified at pH 3 after 1.5 h of tryptic
      digestion. 

PMID- 24106210
TI  - The impact of culturable bacterial community on histopathology in chronic
      rhinosinusitis.
AB  - BACKGROUND: The influence of the microbial community on inflammatory subtype in
      chronic rhinosinusitis (CRS) has been proposed. Superantigen mechanisms
      potentially create a T helper 2 (Th-2)/eosinophilic dominated inflammation as a
      product of local flora rather than an intrinsic mucosal process. The associations
      between culturable bacteria and the histopathology and clinical features of CRS
      patients are described. METHODS: A cross-sectional study involving patients with
      CRS undergoing surgery was undertaken. Middle meatal swabs were performed at
      surgery for microbiological evaluation. Mucosal biopsies were taken and a blinded
      histopathological profile was performed. Disease specific quality of life and
      nasal symptom scores were recorded. The presence of culturable organisms and
      particular pathogens were compared with histopathology and clinical outcomes.
      RESULTS: A total of 95 patients were assessed (48.4% female, mean age 45.6 +/-
      14.0 years), of which 47.3% had a culturable organism. Tissue eosinophilia
      (>10/high-power field [HPF]) was found in 46.1% of these patients and 30.3% had
      neutrophilic infiltrate, with the presence of neither Gram-positive organisms,
      Gram-negative organisms, nor species correlating to pathology subtype. A
      culturable pathogen was a predictor of subepithelial fibrosis (chi(2) = 6.36, p =
      0.04) and Gram-negative bacteria had the strongest association (chi(2) = 18.82, p
      < 0.01). There were no other significant associations with other clinical
      outcomes. CONCLUSION: The culturable bacterial community has little impact on
      histopathology in CRS. While more sensitive tests may detect bacteria in the
      sinuses, the impact of the simple "culturable" bacteria on the underlying
      pathologic process is limited. Changes, such as subepithelial fibrosis, suggest
      colonization may lead to undesirable local mucosal damage and remodeling.

PMID- 24106211
TI  - Diagnostic value of color Doppler ultrasonography of temporal arteries and large
      vessels in giant cell arteritis: a consecutive case series.
AB  - OBJECTIVE: Color Doppler ultrasonography (CDUS) can detect inflammation in the
      vessel wall. No studies have evaluated the examination of the common carotid
      artery by CDUS in the diagnostics of giant cell arteritis (GCA). Our aim was to
      evaluate the combination of CDUS examination of the temporal, axillary, and
      common carotid arteries in the diagnosis of GCA. METHODS: Patients ages >=50
      years who were referred to our department between April 2010 and October 2012 and
      suspected to have GCA were consecutively examined. A positive clinical evaluation
      for GCA 6 months after the first evaluation by 3 rheumatologists was considered
      as the gold diagnostic standard. All patients underwent CDUS of the temporal,
      axillary, and common carotid arteries. A biopsy of the temporal artery was
      performed for most patients. RESULTS: A total of 88 patients were assessed. Forty
      six patients were diagnosed to have GCA by the defined gold standard. Forty-eight
      patients had a positive CDUS of the temporal artery. Forty-six patients diagnosed
      with GCA had a positive CDUS of the temporal, common carotid, and axillary
      arteries (100% sensitivity) and 4 patients had a positive CDUS without having GCA
      (91% specificity). Among the 39 GCA patients that underwent a biopsy, vasculitis
      was observed in 26 patients (66%), yielding a sensitivity of 67% and a
      specificity of 95%. CONCLUSION: CDUS of the common carotid, axillary, and
      temporal arteries had an excellent sensitivity and high specificity to diagnose
      GCA. CDUS has the potential to replace biopsy in ordinary clinical care without
      compromising on sensitivity and specificity.

PMID- 24106209
TI  - Gene therapy on the move.
AB  - The first gene therapy clinical trials were initiated more than two decades ago.
      In the early days, gene therapy shared the fate of many experimental medicine
      approaches and was impeded by the occurrence of severe side effects in a few
      treated patients. The understanding of the molecular and cellular mechanisms
      leading to treatment- and/or vector-associated setbacks has resulted in the
      development of highly sophisticated gene transfer tools with improved safety and
      therapeutic efficacy. Employing these advanced tools, a series of Phase I/II
      trials were started in the past few years with excellent clinical results and no
      side effects reported so far. Moreover, highly efficient gene targeting
      strategies and site-directed gene editing technologies have been developed and
      applied clinically. With more than 1900 clinical trials to date, gene therapy has
      moved from a vision to clinical reality. This review focuses on the application
      of gene therapy for the correction of inherited diseases, the limitations and
      drawbacks encountered in some of the early clinical trials and the revival of
      gene therapy as a powerful treatment option for the correction of monogenic
      disorders.

PMID- 24106212
TI  - Sequence and domain conservation of the coelacanth Hsp40 and Hsp90 chaperones
      suggests conservation of function.
AB  - Molecular chaperones and their associated co-chaperones play an important role in
      preserving and regulating the active conformational state of cellular proteins.
      The chaperone complement of the Indonesian Coelacanth, Latimeria menadoensis, was
      elucidated using transcriptomic sequences. Heat shock protein 90 (Hsp90) and heat
      shock protein 40 (Hsp40) chaperones, and associated co-chaperones were focused
      on, and homologous human sequences were used to search the sequence databases.
      Coelacanth homologs of the cytosolic, mitochondrial and endoplasmic reticulum
      (ER) homologs of human Hsp90 were identified, as well as all of the major co
      chaperones of the cytosolic isoform. Most of the human Hsp40s were found to have
      coelacanth homologs, and the data suggested that all of the chaperone machinery
      for protein folding at the ribosome, protein translocation to cellular
      compartments such as the ER and protein degradation were conserved. Some
      interesting similarities and differences were identified when interrogating
      human, mouse, and zebrafish homologs. For example, DnaJB13 is predicted to be a
      non-functional Hsp40 in humans, mouse, and zebrafish due to a corrupted histidine
      proline-aspartic acid (HPD) motif, while the coelacanth homolog has an intact
      HPD. These and other comparisons enabled important functional and evolutionary
      questions to be posed for future experimental studies.

PMID- 24106213
TI  - Adsorption of HMF from water/DMSO solutions onto hydrophobic zeolites: experiment
      and simulation.
AB  - The adsorption of 5-hydroxymethylfurfural (HMF), DMSO, and water from binary and
      ternary mixtures in hydrophobic silicalite-1 and dealuminated Y (DAY) zeolites at
      ambient conditions was studied by experiments and molecular modeling. HMF and
      DMSO adsorption isotherms were measured and compared to those calculated using a
      combination of grand canonical Monte Carlo and expanded ensemble (GCMC-EE)
      simulations. A method based on GCMC-EE simulations for dilute solutions combined
      with the Redlich-Kister (RK) expansion (GCMC-EE-RK) is introduced to calculate
      the isotherms over a wide range of concentrations. The simulations, using
      literature force fields, are in reasonable agreement with experimental data. In
      HMF/water binary mixtures, large-pore hydrophobic zeolites are much more
      effective for HMF adsorption but less selective because large pores allow water
      adsorption because of H2 O-HMF attraction. In ternary HMF/DMSO/water mixtures,
      HMF loading decreases with increasing DMSO fraction, rendering the separation of
      HMF from water/DMSO mixtures by adsorption difficult. The ratio of the energetic
      interaction in the zeolite to the solvation free energy is a key factor in
      controlling separation from liquid mixtures. Overall, our findings could have an
      impact on the separation and catalytic conversion of HMF and the rational design
      of nanoporous adsorbents for liquid-phase separations in biomass processing.

PMID- 24106216
TI  - Efficacy of crosslinking on tailoring in vivo biodegradability of fibro-porous
      decellularized extracellular matrix and restoration of native tissue structure: a
      quantitative study using stereology methods.
AB  - Cholecyst-derived extracellular matrix (CEM) is a fibro-porous decellularized
      serosal layer of porcine gall-bladder. CEM loses 90% of its weight at 48 h of in
      vitro collagenase digestion, but takes two months to be completely resorbed in
      vivo. Carbodiimide (EDC) crosslinking helps tailoring CEM's in vitro collagenase
      susceptibility. Here, the efficacy of EDC crosslinking on tailoring in vivo
      biodegradability of CEM is reported. CEM crosslinked with 0.0005 and 0.0033 *
      10(3) M of EDC/mg that lose 80% and 0% of their weight respectively to in vitro
      collagenase digestion, were present even after 180 days in vivo. Quantitative
      histopathology using stereology methods confirmed our qualitative observation
      that even a tiny degree of crosslinking can significantly prolong the rate of in
      vivo degradation and removal of CEM. 

PMID- 24106215
TI  - Hypogammaglobulinemia in pediatric systemic lupus erythematosus.
AB  - OBJECTIVE: Systemic lupus erythematosus (SLE) is a systemic autoimmune disease
      typically associated with elevated serum immunoglobulin G (IgG).
      Hypogammaglobulinemia in SLE patients has been attributed to immunosuppressive
      treatment or a transient effect associated with nephrotic syndrome. We
      retrospectively reviewed pediatric SLE patients from a single institution to
      identify patients with hypogammaglobulinemia and risk factors for
      hypogammaglobulinemia. METHODS: A total of 116 pediatric SLE cases from 1997 to
      2011 were reviewed and patients with hypogammaglobulinemia (IgG < 500 mg/dl) were
      identified. The two cohorts were evaluated for association with age, sex,
      presence of lupus nephritis at SLE diagnosis, disease activity at diagnosis,
      initial IgG level, and drug treatment. RESULTS: Eighty-six patients were included
      in our study, with a median age of 15 years and a median follow-up of 39.5
      months. Seven percent (six of 86) of patients had hypogammaglobulinemia with a
      median onset of 27 months (0-72 months) after SLE diagnosis. Significant
      associations were noted for white race (p value 0.029), male sex (p value 0.009),
      and the presence of lupus nephritis at SLE diagnosis (p value 0.004). Use of
      immunosuppressive treatment did not show a statistical association with
      hypogammaglobulinemia, although two of the patients with hypogammaglobulinemia
      did receive rituximab. Most patients with hypogammaglobulinemia received
      intravenous immunoglobulin (IVIG) replacement therapy because of infections
      and/or concern for infection. CONCLUSION: Measurement of immunoglobulin levels
      during treatment in SLE could help identify patients with hypogammaglobulinemia
      who might require more aggressive follow-up to monitor for increased risk of
      infection and need for IVIG treatment. A prospective study is needed to validate
      associated risk factors identified in this study.

PMID- 24106217
TI  - Translating leprosy: the expert and the public in Stanley Stein's anti
      stigmatization campaigns, 1931-60.
AB  - This article examines three campaigns through which patient activist Stanley
      Stein sought to combat the stigmatized connotations of the word "leprosy." In
      1931, soon after starting the first patient newspaper at the U.S. national
      leprosy hospital at Carville, Stein became convinced of the necessity of finding
      an alternative to "leprosy." His ensuing campaign to promote the use of the words
      "Hansen's Disease" to describe the condition from which he and fellow Carville
      patients suffered became his most passionate and life-long project. In the 1950s,
      Stein became involved in efforts to change the translation of "leprosy" in the
      Bible. Finally, in 1960, he waged a campaign to de-stigmatize encyclopedia
      entries on leprosy. These campaigns illustrate how even elevation of the medical
      expert and a seeming disdain for the public can function as a protest of medical
      authority and reveal a presumption that a significant degree of authority
      actually resides with the public. 

PMID- 24106214
TI  - NADPH oxidase and nitric oxide synthase-dependent superoxide production is
      increased in proliferative lupus nephritis.
AB  - OBJECTIVE: Lupus nephritis (LN) is an immune complex-mediated glomerulonephritis.
      Proliferative LN (PLN, ISN/RPS classes III and IV)) often leads to renal injury
      or failure despite traditional induction and maintenance therapy. Successful
      targeted therapeutic development requires insight into mediators of inflammation
      in PLN. Superoxide (SO) and its metabolites are mediators of the innate immune
      response through their ability to mediate reduction-oxidation signaling.
      Endothelial nitric oxide synthase (eNOS) modulates inflammatory responses in
      endothelial cells. We hypothesized that markers of SO production would be
      increased in active PLN and that SO production would be dependent on the activity
      of select enzymes in the renal cortex. METHODS: Patients with systemic lupus
      erythematosus were enrolled at the time of renal biopsy for active LN of all
      classes. Serum collected at baseline was analyzed by HPLC with electrochemical
      detection for markers of SO production (durable modifications of serum protein
      Tyr ultimately requiring SO as a substrate). Renal cortex from MRL/MpJ-FAS(lpr)
      (MRL/lpr) mice with and without functional eNOS was analyzed during active
      disease for superoxide (SO) production with and without inhibitors of SO
      producing enzymes. RESULTS: Serum protein modifications indicative of total SO
      production were significantly higher in patients with PLN. These markers were
      increased in association with more active, inflammatory PLN. Mice lacking
      functional eNOS had 80% higher levels of renal cortical SO during active disease,
      and inhibitors of nitric oxide synthase and NADPH oxidase reduced these levels by
      60% and 77%, respectively. CONCLUSION: These studies demonstrate that SO
      production is unique to active PLN in a NOS and NADPH oxidase-dependent fashion.
      These findings suggest the emulating or augmenting eNOS activity or inhibiting
      NADPH oxidase SO production may be targets of therapy in patients with PLN. The
      markers of SO production used in this study could rationally be used to select SO
      modulating therapies and serve as pharmacodynamic indicators for dose titration.

PMID- 24106221
TI  - Systemic prednisone administration selectively alters granulocyte subsets in
      nasal polyps from aspirin-exacerbated respiratory disease and chronic
      rhinosinusitis patients.
AB  - BACKGROUND: Nasal polyps (NPs) are hallmark inflammatory lesions of sinusitis.
      Despite the spectrum of NP conditions, cellular differences between NPs from
      patients with chronic rhinosinusitis with NPs (CRSwNP) and aspirin-exacerbated
      respiratory disease (AERD) are poorly understood. NPs are associated with
      abundant eosinophils; the contributions of neutrophil and basophil granulocytes
      are less defined. We therefore sought to assess granulocyte subpopulations, and
      differential effects following prednisone pretreatment, within NPs of CRSwNP and
      AERD patients. METHODS: NPs, adjacent ethmoid sinus tissue, and peripheral blood
      mononuclear cells (PBMCs) were obtained from patients undergoing endoscopic sinus
      surgery. Samples from 5 cohorts: CRSwNP +/- prednisone (n = 6 each), AERD +/-
      prednisone (n = 6 each), and controls (n = 9), were analyzed by high-dimensional
      flow cytometry to gate granulocyte populations. Specimens were also assessed
      using immunohistochemistry (IHC) staining. RESULTS: Systemic prednisone
      administration was associated with a lower frequency of eosinophils (p < 0.0001,
      n = 6) in NPs in both CRSwNP and AERD patients, whereas a decrease in neutrophils
      (p = 0.0070, n = 6) in NPs was only observed in CRSwNP patients after prednisone
      treatment. In contrast, steroids do not alter basophil proportions (p = 0.48, n =
      6) within NPs from either group. No significant shift in granulocyte subsets
      after steroid treatment was identified in the adjacent ethmoid mucosa or PBMCs
      from the same patients. Immunohistochemistry (IHC) staining supported these
      findings. CONCLUSION: Granulocyte subpopulations are focally affected within NPs
      by systemic steroid exposure, without notable granulocyte alterations in the
      surrounding regional tissues. These data provide direct insights into the
      cellular effects of routine prednisone exposure in CRS patients, and highlight a
      unique microenvironment present within NP lesions.

PMID- 24106222
TI  - Liver gene therapy by lentiviral vectors reverses anti-factor IX pre-existing
      immunity in haemophilic mice.
AB  - A major complication of factor replacement therapy for haemophilia is the
      development of anti-factor neutralizing antibodies (inhibitors). Here we show
      that liver gene therapy by lentiviral vectors (LVs) expressing factor IX (FIX)
      strongly reduces pre-existing anti-FIX antibodies and eradicates FIX inhibitors
      in haemophilia B mice. Concomitantly, plasma FIX levels and clotting activity
      rose to 50-100% of normal. The treatment was effective in 75% of treated mice.
      FIX-specific plasma cells (PCs) and memory B cells were reduced, likely because
      of memory B-cell depletion in response to constant exposure to high doses of FIX.
      Regulatory T cells displaying FIX-specific suppressive capacity were induced in
      gene therapy treated mice and controlled FIX-specific T helper cells. Gene
      therapy proved safer than a regimen mimicking immune tolerance induction (ITI) by
      repeated high-dose FIX protein administration, which induced severe anaphylactoid
      reactions in inhibitors-positive haemophilia B mice. Liver gene therapy can thus
      reverse pre-existing immunity, induce active tolerance to FIX and establish
      sustained FIX activity at therapeutic levels. These data position gene therapy as
      an attractive treatment option for inhibitors-positive haemophilic patients.

PMID- 24106223
TI  - Cost effectiveness of training rural providers to perform joint injections.
AB  - OBJECTIVE: Community-based outpatient clinics (CBOCs) have been established by
      the Department of Veterans Affairs (VA) to provide primary care services to
      veterans living in remote and rural regions. The objective of this study was to
      evaluate the cost effectiveness of training rural primary care providers to
      perform knee injections in CBOCs, thereby avoiding referring the patient to an
      urban medical center for an injection by rheumatology or orthopedic specialists.
      METHODS: We developed a decision-analysis model to compare costs and outcomes
      between rural providers who are trained to perform knee injections versus those
      who are not trained, therefore requiring a referral to a specialist to provide
      the injections. The model was run separately using costs from the perspective of
      the VA as well from the patient's perspective. The effectiveness outcome was
      quality-adjusted life years (QALYs). Probabilistic sensitivity analyses were
      performed using 10,000 second-order Monte Carlo simulations. RESULTS: In our base
      case analyses, the incremental cost-effectiveness ratio for trained rural
      providers was $21,190/QALY using costs from the perspective of the VA and
      $205/QALY using costs from the patient's perspective. Training rural providers
      was cost effective in 74.4% and 93.6% of 10,000 Monte Carlo simulations at a
      willingness-to-pay threshold of $50,000/QALY from the perspectives of the VA and
      the patient, respectively. CONCLUSION: Training rural providers to perform knee
      injections for patients with knee pain secondary to osteoarthritis appears cost
      effective using the commonly used threshold of $50,000/QALY if more than 20 such
      patients per year are seen at rural primary care clinics. These results provide
      support for our ongoing efforts to implement such a training program.

PMID- 24106224
TI  - Enhanced visible-light hydrogen-production activity of copper-modified ZnxCd(1
      x)S.
AB  - Copper modification is an efficient way to enhance the photocatalytic activity of
      ZnS-based materials; however, the mechanisms of Cu(2+) surface and bulk
      modifications for improving the activity are quite different. In this work, two
      different synthetic pathways were devised to prepare surface and bulk Cu(2+)
      modified Znx Cd1-x S photocatalysts through cation-exchange and coprecipitation
      methods, respectively. Different Cu(2+) modifications brought different effects
      on the phase structure, morphology, surface area, optical property, as well as
      the photocatalytic H2-production activity of the final products. The optimized
      Cu(2+)-surface-modified Znx Cd1-x S photocatalyst has a high H2-production rate
      of 4638.5 MUmolh(-1) g(-1) and an apparent quantum efficiency of 20.9% at 420 nm,
      exceeding that of Cu(2+)-bulk-modified catalyst at the same copper content.
      Cu(2+) surface modification not only brings a new electron-transferring pathway
      (interfacial charge transfer), but also produces new surface active sites for H2
      evolution, reducing the recombination rate of photogenerated charge carriers.

PMID- 24106225
TI  - Risk of redocumenting penicillin allergy in a cohort of patients with negative
      penicillin skin tests.
AB  - BACKGROUND: Even though electronic documentation of allergies is critical to
      patient safety, inaccuracies in documentation can potentiate serious problems.
      Prior studies have not evaluated factors associated with redocumenting penicillin
      allergy in the medical record despite a proven tolerance with a penicillin skin
      test (PST). OBJECTIVE: Assess the prevalence of reinstating inaccurate allergy
      information and associated factors thereof. DESIGN: We conducted a retrospective
      observational study from August 1, 2012 to July 31, 2013 of patients who
      previously had a negative PST. We reviewed records from the hospital, long-term
      care facilities (LTCF), and primary doctors' offices. SETTING: Vidant Health, a
      system of 10 hospitals in North Carolina. SUBJECTS: Patients with proven
      penicillin tolerance rehospitalized within a year period from the PST.
      MEASUREMENTS: We gauged hospital reappearances, penicillin allergy
      redocumentation, residence, antimicrobial use, and presence of dementia or
      altered mentation. RESULTS: Of the 150 patients with negative PST, 55 (37%)
      revisited a Vidant system hospital within a 1-year period, of whom 21 were LTCF
      residents. Twenty (36%) of the 55 patients had penicillin allergy redocumented
      without apparent reason. Factors associated with penicillin allergy
      redocumentation included age >65 years (P = 0.011), LTCF residence (P = 0.0001),
      acutely altered mentation (P < 0.0001), and dementia (P < 0.0001). Penicillin
      allergy was still listed in all 21 (100%) of the LTCF records. CONCLUSIONS: At
      our hospital system, penicillin allergies are often redocumented into the medical
      record despite proven tolerance. The benefits of PST may be limited by
      inadequately removing the allergy from different electronic/paper hospital, LTCF,
      primary physician, and community pharmacy records.

PMID- 24106226
TI  - Preparation of biodegradable peptide nanospheres with hetero PEG brush surfaces.
AB  - Controlled hetero poly(ethylene glycol) (PEG) brushes composed of higher and
      lower molecular weight PEG chains are for the first time prepared onto
      biodegradable peptide nanospheres. Hence, the PEG chains are easily detached and
      re-attached based on the thiol-disulfide chemistry of the interfacial disulfide
      bonds of PEG-SS-peptide nanospheres. The density of the 1(st) PEG with a
      molecular weight of 2000 (M-w = 2k) is controlled by altering the reduction
      conditions. Subsequently, 2(nd) PEG chains with a higher M-w (from 5000 to 20
      000) are constructed by oxidative reactions. Hetero PEG2k 60%/PEG5k 40%
      demonstrates about 2.5-fold greater protein resistance than homo PEG2k 100% or
      PEG5k 40%, and exceptional dispersion stability in serum for over three weeks.
      Hetero PEG brush peptide nanospheres will be useful as bioinert drug carriers for
      biomedical applications. 

PMID- 24106227
TI  - Photo quiz. A Mauritanian woman with a swollen knee.

PMID- 24106231
TI  - The effect of head position on the distribution of topical nasal medication using
      the Mucosal Atomization Device: a cadaver study.
AB  - BACKGROUND: The Mucosal Atomization Device (MAD) distributes medication
      throughout the paranasal sinuses for patients with chronic rhinosinusitis (CRS).
      Determining the optimal head position is important to ensure maximal delivery of
      medication to the sinus cavities. The objective of this work was to determine the
      effect of the lying-head-back (LHB) and head-down and forward (HDF) position, on
      the distribution of topical nasal medication via MAD in cadaver specimens.
      METHODS: Twenty specimens having received complete functional endoscopic sinus
      dissection were chosen. The MAD was used to administer 2 mL of fluorescein
      impregnated saline solution through the nose in both the LHB and HDF positions.
      Fluorescein was identified on 11 predetermined anatomical areas using a blue
      light filter. Three blinded investigators assessed endoscopic images to determine
      the presence of fluorescein. RESULTS: A total of 440 anatomical locations (n = 20
      cadavers) received administration of the fluorescein nasal spray in the LHB or
      HDF position. LHB position had significantly greater total distribution to all
      pertinent anatomical sites than the HDF position (76% vs 41%; p < 0.001; 95%
      confidence interval [CI], 0.26-0.44). The proportion of staining was
      significantly greater for the ethmoid (p = 0.11; 95% CI, 0.05-0.66), frontal (p <
      0.01; 95% CI, 0.20-0.80), and sphenoid sinuses (p = 0.03; 95% CI, 0.07-0.73) when
      compared to the HDF position. CONCLUSION: A greater distribution of medication to
      the sinonasal cavities was observed in the LHB position compared to the HDF
      position. These areas are of particular clinical relevance in postsurgical
      patients with refractory CRS.

PMID- 24106230
TI  - Effective gene therapy for haemophilic mice with pathogenic factor IX antibodies.
AB  - Formation of pathogenic antibodies is a major problem in replacement therapies
      for inherited protein deficiencies. For example, antibodies to coagulation
      factors ('inhibitors') seriously complicate treatment of haemophilia. While
      immune tolerance induction (ITI) protocols have been developed, inhibitors
      against factor IX (FIX) are difficult to eradicate due to anaphylactic reactions
      and nephrotic syndrome and thus substantially elevate risks for morbidity and
      mortality. However, hepatic gene transfer with an adeno-associated virus (AAV)
      serotype 8 vector expressing FIX (at levels of >=4% of normal) rapidly reversed
      pre-existing high-titre inhibitors in haemophilia B mice, eliminated antibody
      production by B cells, desensitized from anaphylaxis (even if protein therapy was
      resumed) and provided long-term correction. High levels of FIX protein suppressed
      memory B cells and increased Treg induction, indicating direct and indirect
      mechanisms of suppression of inhibitor formation. Persistent presence of Treg was
      required to prevent relapse of antibodies. Together, these data suggest that
      hepatic gene transfer-based ITI provides a safe and effective alternative to
      eradicate inhibitors. This strategy may be broadly applicable to reversal of
      antibodies in different genetic diseases.

PMID- 24106232
TI  - Gold-nanoparticle-based catalysts for the oxidative esterification of 1,4
      butanediol into dimethyl succinate.
AB  - The oxidation of 1,4-butanediol and butyrolactone have been investigated by using
      supported gold, palladium and gold-palladium nanoparticles. The products of such
      reactions are valuable chemical intermediates and, for example, can present a
      viable pathway for the sustainable production of polymers. If both gold and
      palladium were present, a significant synergistic effect on the selective
      formation of dimethyl succinate was observed. The support played a significant
      role in the reaction, with magnesium hydroxide leading to the highest yield of
      dimethyl succinate. Based on structural characterisation of the fresh and used
      catalysts, it was determined that small gold-palladium nanoalloys supported on a
      basic Mg(OH)2 support provided the best catalysts for this reaction.

PMID- 24106233
TI  - Cardiac tissue characterization and the diagnostic value of cardiovascular
      magnetic resonance in systemic connective tissue diseases.
AB  - OBJECTIVE: Accurate diagnosis of cardiovascular involvement in connective tissue
      diseases (CTDs) remains challenging. We hypothesized that cardiovascular magnetic
      resonance (CMR) demonstrates cardiac lesions in symptomatic CTD patients with
      normal echocardiography. METHODS: CMR from 246 CTD patients with typical cardiac
      symptoms (TCS; n = 146, group A) or atypical cardiac symptoms (ATCS; n = 100,
      group B) was retrospectively evaluated. Group A included 9 patients with
      inflammatory myopathy (IM), 35 with sarcoidosis, 30 with systemic sclerosis
      (SSc), 14 with systemic lupus erythematosus (SLE), 10 with rheumatoid arthritis
      (RA), and 48 with small vessel vasculitis. Group B included 25 patients with RA,
      20 with SLE, 20 with sarcoidosis, 15 with SSc, 10 with IM, and 10 with small
      vessel vasculitis. CMR was performed by 1.5T; left ventricular ejection fraction,
      T2 ratio (edema imaging), and late gadolinium enhancement (LGE; fibrosis imaging)
      were evaluated. Acute and chronic lesions were characterized as LGE positive plus
      T2 ratio >2 and T2 ratio <=2, respectively. According to LGE, lesions were
      characterized as diffuse subendocardial, subepicardial, and
      subendocardial/transmural due to vasculitis, myocarditis, and myocardial
      infarction, respectively. A stress study by dobutamine echocardiography or
      stress, nuclear, or adenosine CMR was performed in CTD patients with negative
      rest CMR. RESULTS: Abnormal CMR was identified in 32% (27% chronic) and 15% (12%
      chronic) of patients with TCS and ATCS, respectively. Lesions due to vasculitis,
      myocarditis, and myocardial infarction were evident in 27.4%, 62.6%, and 9.6% of
      CTD patients, respectively. Stress studies in CTD patients with negative CMR
      revealed coronary artery disease in 20%. CONCLUSION: CMR in symptomatic CTD
      patients with normal echocardiography can assess disease acuity and identify
      vasculitis, myocarditis, and myocardial infarction.

PMID- 24106234
TI  - Health-Related Quality of Life in HIV-Infected and At-Risk Women: The Impact of
      Illicit Drug Use and Hepatitis C on a Community Preference Weighted Measure.
AB  - PURPOSE: To assess the impact of illicit drug use and chronic hepatitis C virus
      (HCV) on health-related quality of life (HRQoL) in women with HIV or at risk for
      HIV infection. METHODS: Cross-sectional analysis of data from the Women's
      Interagency Health Study (WIHS) of women with HIV (n = 2508) and at high risk of
      HIV infection (n = 889) in the US. A Short-Form-6D (SF-6D) HRQoL measure derived
      from the Medical Outcomes Study-HIV (MOS-HIV) questionnaire, HIV infection
      status, CD4 cell count (a measure of immune status), antiretroviral treatment,
      current illicit drug use (heroin and/or cocaine), and HCV status were assessed at
      a recent study visit. We developed multivariate linear regression models
      adjusting for age, race/ethnicity, education, and testing for interactions.
      RESULTS: HIV-infected women with <=200 CD4 cells/uL had lower mean HRQoL scores
      (0.69) than either HIV-infected women with >200 CD4 cells/uL (0.78) or HIV
      uninfected women (0.80) (P < 0.01). In multivariate analysis, illicit drug use,
      chronic HCV, and low CD4 count were independently associated with lower HRQoL.
      There was a differential effect of HCV and illicit drug use for HIV-infected
      women depending on CD4 cell count: HIV-infected women with >200 CD4 cells/uL had
      a significantly greater reduction in HRQoL associated with illicit drug use (
      0.063) and chronic HCV (-0.036) than women with <=200 CD4 cells/uL (-0.017, 
      0.005 respectively). CONCLUSIONS: Poorly controlled HIV, illicit drug use, and
      chronic HCV are associated with lower HRQoL. Illicit drug use and chronic HCV
      have greater HRQoL impacts for HIV-infected women with well-controlled HIV versus
      those with poorly controlled HIV, which may affect clinical and policy
      priorities.

PMID- 24106236
TI  - Development of multiple stimuli responsive magnetic polymer nanocontainers as
      efficient drug delivery systems.
AB  - Magnetic nanodevices based on poly[(methacrylic acid)-co-(N-isopropylacrylamide)]
      [P(MAA-co-NIPAAm)] are prepared and used as drug delivery systems employing
      daunorubicin (DNR) as a model drug. The magnetic nanocontainers exploit the pH,
      temperature, and magnetic response of the polymeric shell constituents and
      magnetic nanoparticles, respectively, for controlled pH, temperature and
      alternating magnetic field triggered drug release. The in vitro cytotoxicity of
      both DNR-loaded and empty nanocontainers is examined on MCF-7 breast cancer cells
      along with the intracellular distribution of DNR. The results show that the DNR
      loaded nanocontainers have an anti-tumor effect comparable to the free drug. The
      current observations provide important information for potent drug delivery and
      release systems. 

PMID- 24106235
TI  - Participation of very old adults in health care decisions.
AB  - BACKGROUND: Some elderly people receive tests or interventions from which they
      have low likelihood of benefit or for which the goal is not aligned with their
      values. Engaging these patients in the decision process is one potential approach
      to improve the individualization of care. Yet some clinicians perceive and some
      survey data suggest that older adults prefer not to participate in the decision
      making process. Those preferences, however, may be formed based on an experience
      in which factors, such as communication issues, were barriers to participation.
      Our goal was to shed light on the experience of very old adults in health care
      decision making from their own point of view to deepen our understanding of their
      potentially modifiable barriers to participation. DESIGN: and METHODS:
      Semistructured interviews of participants aged 80 and older (n = 29, 59% women
      and 21% black) were analyzed using the constant comparative method in a grounded
      theory approach to describe decision making in clinic visits from the patient's
      perspective. RESULTS: The average age was 84 years (range, 80-93); each described
      an average of 6.4 decision episodes. Active participation was highly variable
      among subjects. Marked differences in participation across participants and by
      type of decision--surgery, medications, diagnostic procedures, routine testing
      for preventive care--highlighted barriers to greater participation. The most
      common potentially modifiable barriers were the perception that there were no
      options to consider, low patient activation, and communication issues.
      CONCLUSIONS: The experience of very old adults highlights potentially modifiable
      barriers to greater participation in decision making. To bring very old patients
      into the decision process, clinicians must modify interviewing skills and spend
      additional time eliciting their values, goals, and preferences.

PMID- 24106237
TI  - The effect of lattice strain on the catalytic properties of Pd nanocrystals.
AB  - The effect of lattice strain on the catalytic properties of Pd nanoparticles is
      systematically studied. Synthetic strategies for the preparation of a series of
      shape-controlled Pd nanocrystals with lattice strain generated from different
      sources has been developed. All of these nanocrystals were created with the same
      capping agent under similar reaction conditions. First, a series of Pd
      nanoparticles was synthesized that were enclosed in {111} surfaces: Single
      crystalline Pd octahedra, single-crystalline AuPd core-shell octahedra, and
      twinned Pd icosahedra. Next, various {100}-terminated particles were synthesized:
      Single-crystalline Pd cubes and single-crystalline AuPd core-shell cubes.
      Different extents of lattice strain were evident by comparing the X-ray
      diffraction patterns of these particles. During electrocatalysis, decreased
      potentials for CO stripping and increased current densities for formic-acid
      oxidation were observed for the strained nanoparticles. In the gas-phase
      hydrogenation of ethylene, the activities of the strained nanoparticles were
      lower than those of the single-crystalline Pd nanoparticles, perhaps owing to a
      larger amount of cetyl trimethylammonium bromide on the surface. 

PMID- 24106238
TI  - Specific inhalation challenge with flour induced release of brain-derived
      neurotrophic factor in nasal fluid.
AB  - BACKGROUND: Neurotrophins may play a role in the pathophysiology of allergic
      occupational rhinitis (OR). We sought to investigate whether an immediate
      allergic reaction that induces nasal inflammation is also able to induce changes
      in levels of brain-derived neurotrophic factor (BDNF) in nasal lavage (NAL) fluid
      from patients with allergic OR. METHODS: Ten patients sensitized to flour
      underwent control and active specific inhalation challenge (SIC) on consecutive
      days. Nasal response to SIC was monitored with acoustic rhinometry and symptoms
      recording. NAL was performed before and 30 minutes, 6 hours, and 24 hours after
      control and active challenge for the assessment of levels of BDNF and
      inflammatory cells in NAL fluid. RESULTS: In contrast to control day, flour
      challenge induced immediate clinical reactions in all subjects. After flour
      challenge, a significant increase in levels of BDNF in NAL fluid was observed at
      6 hours after challenge (p < 0.05). Also, a significant increase in the number of
      eosinophils in NAL fluid at 30 minutes (p < 0.01), 6 hours (p < 0.01), and 24
      hours (p = 0.05) postchallenge was observed. Also, levels of BDNF in NAL fluid
      were significantly higher at 30 minutes after flour challenge (p = 0.02) in
      comparison to levels on the control day at the same postchallenge time. A
      marginally significant positive correlation between BDNF levels and eosinophil
      counts at 30 minutes (r = 0.60, p = 0.06) and at 6 hours (r = 0.50, p = 0.08)
      after flour challenge was noted. CONCLUSION: We showed that BDNF is released in
      nasal fluid after SIC with flour. Results support the suggestion that
      neurotrophins may play a role in the pathogenesis of allergic OR.

PMID- 24106239
TI  - Emerging therapies for the treatment of hepatitis C.
AB  - Opportunities to treat infection with hepatitis C virus (HCV) are evolving
      rapidly. From the introduction of interferon-alpha monotherapy in 1992 to the
      approval of telaprevir- and boceprevir-based triple therapies with pegylated
      interferon-alpha and ribavirin in 2011, the chances of curing patients infected
      with HCV genotype 1 have improved from <10% to approximately 70%. Significant
      further improvements are on the horizon, which may well cure virtually all
      hepatitis C patients with an all-oral, interferon-free regimen in the very near
      future. These exciting developments are reviewed in the present article.

PMID- 24106240
TI  - Combined surface micropatterning and reactive chemistry maximizes tissue adhesion
      with minimal inflammation.
AB  - The use of tissue adhesives for internal clinical applications is limited due to
      a lack of materials that balance strong adhesion with biocompatibility. The use
      of substrate topography is explored to reduce the volume of a highly reactive and
      toxic glue without compromising adhesive strength. Micro-textured patches coated
      with a thin layer of cyanoacrylate glue achieve similar adhesion levels to
      patches employing large amounts of adhesive, and is superior to the level of
      adhesion achieved when a thin coating is applied to a non-textured patch. In vivo
      studies demonstrate reduced tissue inflammation and necrosis for patterned
      patches with a thinly coated layer of reactive glue, thus overcoming a
      significant challenge with existing tissue adhesives such as cyanoacrylate.
      Closure of surgical stomach and colon defects in a rat model is achieved without
      abdominal adhesions. Harnessing the synergy between surface topography and
      reactive chemistry enables controlled tissue adhesion with an improved
      biocompatibility profile without requiring changes in the chemical composition of
      reactive tissue glues. 

PMID- 24106241
TI  - Characterization of trans-septal activation during septal pacing: criteria for
      identification of intramural ventricular tachycardia substrate in nonischemic
      cardiomyopathy.
AB  - BACKGROUND: Identification of intramural basal-septal ventricular tachycardia
      (VT) substrate is challenging in nonischemic cardiomyopathy. We sought to (1)
      characterize normal/abnormal trans-septal right ventricular (RV) to left
      ventricular activation; (2) assess the effect of opposite RV pacing on left
      ventricular septal bipolar electrograms (EGMs); and (3) establish criteria for
      the identification of intramural septal VT substrate. METHODS AND RESULTS:
      Endocardial activation mapping and local EGM assessment of the left
      interventricular septum was performed during RV basal septal pacing in 40
      patients undergoing VT ablation with no evidence of septal scar (group 1, n=14)
      and with septal scar (group 2, n=26) defined by low septal unipolar voltage (<8.3
      mV) and delayed enhancement on cardiac MRI with/without abnormal bipolar voltage
      (<1.5 mV) in sinus rhythm. Left ventricular trans-septal activation time was
      prolonged in Group 2 compared with Group 1 (55.3+/-33.0 versus 25.7+/-8.8 ms;
      P=0.003). In 6 group 2 patients, left ventricular septal breakthrough was
      displaced to the scar border. During RV pacing, group 2 had fractionated (8.8%),
      late (2.8%), and split (5.7%) EGMs not seen in group 1. Trans-septal activation
      >40 ms (sensitivity 60%, specificity 100%; P<0.001) and EGM duration >95 ms
      during pacing (sensitivity 22%, specificity 91%; P<0.001) identified septal scar
      (13/26 pts). CONCLUSIONS: In patients with nonischemic cardiomyopathy, VT and
      septal scar, delayed transmural conduction time (>40 ms) and fractionated, late,
      split, and wide (>95 ms) bipolar EGMs during RV basal pacing identify intramural
      VT substrate. In select cases, the basal septum appears compartmentalized as the
      stimulated wavefront is rerouted to the scar border.

PMID- 24106242
TI  - Estrogen receptor 1 gene rs2295193 polymorphism and anorexia nervosa: new data
      and meta-analysis.
AB  - INTRODUCTION: Estrogen plays essential roles in the regulation of food intake,
      adiposity, and body weight control. The estrogen alpha receptor, encoded by
      estrogen receptor 1 gene (ESR1), has been implicated with anorexia nervosa (AN).
      A previous study indicated that the rs2295193 polymorphism in ESR1 may confer a
      genetic susceptibility to AN. METHODS: In a case-control study, we assessed 195
      AN probands and 93 healthy controls; 99 trios were studied in a family-based
      association analysis through genotyping the rs2295193 polymorphism in ESR1.
      Additionally, we carried out a meta-analysis of the combined sample groups.
      RESULTS: There were no significant differences in the genotype or allele
      frequencies of the rs2295193 polymorphism between the AN and control groups (Ps >
      0.05). In the transmission disequilibrium test (TDT) analyses, there was no
      evidence for biased transmission of the G allele of rs2295193 polymorphism (P =
      0.32). In female-only samples, no significant association was observed between
      the rs2295193 polymorphism and AN in either case-control or transmission
      disequilibrium test analyses (Ps > 0.05). The meta-analysis revealed that no
      excess of transmission of the G allele in AN families (pooled odds ratio = 1.10,
      P = 0.79). DISCUSSION: Meta-analytically combined evidence from the present
      genotyping and the literature showed that rs2295193 polymorphism in ESR1 is not a
      major genetic susceptibility factor in AN.

PMID- 24106243
TI  - Preparation of sustainable photocatalytic materials through the valorization of
      industrial wastes.
AB  - A new value-added material was developed from wastes to aim for appropriate waste
      management and sustainable development. This paper reports the valorization of
      industrial sandblasting operation wastes (SOWs) as new photocatalytic materials.
      This waste is composed of Fe2 O3 (60.7 %), SiO2 (29.1 %), and Al2 O3 (3.9 %) as
      the main components. The high presence of iron oxides was used to develop
      photocatalytic properties through their thermal transformation into alpha-Fe2 O3
      . The new product, SOW-T, exhibited a good behavior towards the photochemical
      degradation of organic dyes. The preparation of advanced photocatalytic materials
      that exhibit self-cleaning and depolluting properties was possible by the
      inclusion of SOW-T and TiO2 in a cement-based mortar. The synergy observed
      between both materials enhanced their photocatalytic action. To the best of our
      knowledge, this is the first report that describes the use of transformed wastes
      based on iron oxide for the photochemical oxidation of NOx gases. 

PMID- 24106244
TI  - Comparison of tulathromycin, azithromycin and azithromycin-rifampin for the
      treatment of mild pneumonia associated with Rhodococcus equi.
AB  - The objectives of the present study were to determine the relative efficacy of
      tulathromycin, azithromycin, or azithromycin with rifampin for the treatment of
      pulmonary abscesses on a farm with endemic infections caused by Rhodococcus equi.
      Foals with ultrasonographic evidence of pulmonary abscesses (abscess score 8.0-15
      cm; n=120) were randomly allocated in four equal treatment groups: (1)
      tulathromycin intramuscularly; (2) azithromycin monotherapy, orally; (3)
      azithromycin with rifampin, orally; (4) saline intramuscularly as a placebo.
      Physical examination and thoracic ultrasonography were performed by individuals
      unaware of treatment group assignment. Foals that worsened were removed from the
      study. The proportion of foals that recovered without the need for a change in
      therapy was significantly higher for foals treated with azithromycin (29 of 30)
      or azithromycin with rifampin (28 of 30) than for foals treated with a placebo
      (20 of 30). Additionally, azithromycin or azithromycin with rifampin resulted in
      a significantly faster decrease in the number of abscesses and abscess score
      compared with a placebo. The proportion of foals treated with tulathromycin that
      recovered (27 of 30) was not significantly different from that of foals treated
      with a placebo. Azithromycin alone or in combination with rifampin was beneficial
      in the study population. 

PMID- 24106245
TI  - Vacuolar meningioma: a new and rare variant of canine meningioma.

PMID- 24106246
TI  - An association between rainfall and bovine TB in Wicklow, Ireland.

PMID- 24106247
TI  - Canine distemper virus antibody test alone increases misdiagnosis of distemper
      encephalitis.

PMID- 24106248
TI  - Natural border disease virus infection in feedlot lambs.

PMID- 24106249
TI  - Evaluation of serum neutrophil gelatinase-associated lipocalin (NGAL) activity in
      dogs with chronic kidney disease.

PMID- 24106250
TI  - Digital dermatitis in beef cattle.

PMID- 24106252
TI  - Why institutional review board approval.

PMID- 24106251
TI  - Distribution of serotypes and genotypes of Salmonella enterica species in French
      pig production.
AB  - The population of Salmonella found at various stages of pig production in France
      was characterised to analyse the distribution and spread of Salmonella in the pig
      production chain. We serotyped and genotyped by PFGE 174 isolates collected from
      breeding pigs from breeding farms, 163 collected from breeding pigs from
      production farms, and 325 collected from fattening pigs. Forty-seven serovars and
      110 genotypes were identified. The major serovars were S Derby (263 isolates) and
      S Typhimurium (162 isolates). The percentage of S Derby isolates decreased
      slightly through the production system (44.3, 41.1 per cent and 36.5 per cent)
      and 79.1 per cent of the S Derby isolates were distributed in the five genotypes
      common to all three stages. The percentage of S Typhimurium isolates was high for
      slaughter pigs (40.8 per cent) and 43 of the 46 S Typhimurium genotypes were only
      identified at this stage. Distributions of S Derby and S Typhimurium between
      breeding and fattening pigs were different. S Derby was found throughout the pig
      production pyramid, suggesting that this serotype may be transmitted by the
      transfer of animals between herds. The presence of multiple S Typhimurium
      genotypes in fattening pigs suggests that there were many sources of
      contamination at this stage, with fattening pigs having higher levels of exposure
      and/or sensitivity to this serotype. 

PMID- 24106253
TI  - Understanding the underactive bladder.

PMID- 24106254
TI  - A review of the literature informing affordable, available wound management
      choices for rural areas of tropical developing countries.
AB  - Health professionals are often absent in rural areas of tropical developing
      countries. Current wound management in this environment is costly and largely
      ineffective. Achieving effective wound management in this setting will require
      educating the lay health providers who manage wounds in villages. Two extensive
      literature searches were conducted using CINAHL and Medline with no date,
      geographic, or language restrictions. The question, "What is the evidence base
      for topical wound treatments and dressings that are affordable and available in
      developing countries?" was addressed by critically evaluating all 18 identified
      clinical studies and reviews. The results suggest that a moist wound environment
      can be maintained using improvised dressings such as banana leaves, saline-soaked
      furniture foam, and food wrap, and that these choices are superior to many
      commercial dressings. Some varieties of honey, papaya pulp, EUSOL, and
      lubricating jelly are effective, affordable substances for treating and debriding
      wounds. Papaya pulp can be unsafe if not very closely monitored. No studies
      addressing the second question, "What are the topical wound management
      interventions currently being used in rural areas of tropical developing
      countries?" were found. However, 13 articles that could guide the design of
      research studies in this field were identified and are reviewed here. This
      literature describes a wide variety of wound prevention and management methods,
      some known to be deleterious for healing. These two literature reviews reveal the
      large gaps in the evidence base on available and affordable wound treatment
      options for rural patients in developing countries. Future research should
      address these gaps. 

PMID- 24106255
TI  - Developing and integrating a practice model for health finance reform into wound
      healing programs: an examination of the triple aim approach .
AB  - Throughout the United States, government and private payers are exploring new
      payment models such as accountable care organizations and shared savings
      agreements. These models are widely based on the construct of the Triple Aim, a
      set of three principles for health services reform: improving population-based
      outcomes, improving patient care experiences, and reducing costs through better
      delivery systems. Wound programs may adapt to the new health financing
      environment by incorporating initiatives known to promote the Triple Aim, such as
      diabetes amputation reduction and pressure ulcer prevention programs, and by
      rethinking how health services can best be delivered to meet these new criteria.
      The existing literature supports that programmatic approaches can improve care,
      quality, and cost, especially in the field of diabetic foot ulcers. Wound healing
      programs have opportunities to develop new business plan models that provide
      quality, cost-efficient care to their patient population and to be leaders in the
      development of new types of partnerships with payers and health delivery
      organizations. 

PMID- 24106256
TI  - Educating nurses for the twenty-first century abilities-based outcomes and
      assessing student learning in the context of democratic professionalism.
AB  - This article describes recent work in implementing a framework of abilities-based
      learning outcomes and related practices for assessing student learning in a
      Canadian Baccalaureate nursing degree program. The authors describe steps in
      implementing an abilities-based paradigm for nursing education, and subsequently
      developing an assessment framework based on abilities-based learning outcomes.
      The discussion reviews theoretical and policy-level influences involved in this
      initiative. The curriculum work is also discussed in terms of current trends in
      higher education emphasizing the assessment of student learning. The discussion
      concludes by linking these efforts to recent calls for a paradigm shift in the
      preparation of professionals, noting how the assessment of student learning can
      contribute to democratic professional formation in nursing.

PMID- 24106257
TI  - Medication and participation: A qualitative study of patient experiences with
      antipsychotic drugs.
AB  - Patient autonomy is recognised within mental healthcare, although the capacity to
      participate in one's own treatment planning is often reduced during a psychotic
      crisis. The patient may not be sufficiently competent to give consent or express
      preferences at the time treatment decisions are made. Nine participants were
      interviewed shortly after a crisis. We discussed participation in the treatment
      planning and recovery process with particular emphasis on interactions with
      professionals and understanding treatment. The participants recognised the need
      for drugs and mental healthcare but emphasised the need for better cooperation
      and communication. To facilitate the development of patient autonomy, we
      recommend an increased emphasis on providing information and participating in a
      dialogue about drug treatment options. This could counteract many of the negative
      experiences reported. The use of debriefing during hospitalisation and following
      coercion can be a practical tool for clarifying patient preferences and mutual
      understanding. 

PMID- 24106258
TI  - Can quality from a care ethical perspective be assessed? A review.
AB  - BACKGROUND: Ethics-of-care theories contain important notions regarding the
      quality of care; however, until now, concrete translations of the insights into
      instruments are lacking. This may be a result of the completely different type of
      epistemology, theories and concepts used in the field of quality of care
      research. OBJECTIVES: Both the fields of 'ethics of care' and 'quality of care'
      aim for improvement of care; therefore; insights could possibly meet by focusing
      on the following question: How could ethics-of-care theories contribute to better
      quality in care at a measurement level? This study reviews existing instruments
      with the aim of bridging this gap and examines the evidence of their psychometric
      properties, feasibility and responsiveness. RESEARCH DESIGN: A systematic search
      of the literature was undertaken using multiple electronic databases covering
      January 1990 through May 2012. METHOD AND FINDINGS: Of the 3427 unique references
      identified, 55 studies describing 40 instruments were selected. Using a
      conceptual framework, an attempt was made to distinguish between related concepts
      and to group available instruments measuring different types of concepts. A total
      of 13 instruments that reflect essential aspects of ethics-of-care theory were
      studied in greater detail, and a quality assessment was conducted. CONCLUSION:
      Three promising qualitative instruments were found, which follow the logic of the
      patient and take their specific context into account.

PMID- 24106259
TI  - Healthcare professionals' perspectives on environmental sustainability.
AB  - BACKGROUND: Human health is dependent upon environmental sustainability. Many
      have argued that environmental sustainability advocacy and environmentally
      responsible healthcare practice are imperative healthcare actions. RESEARCH
      QUESTIONS: What are the key obstacles to healthcare professionals supporting
      environmental sustainability? How may these obstacles be overcome? RESEARCH
      DESIGN: Data-driven thematic qualitative analysis of semi-structured interviews
      identified common and pertinent themes, and differences between specific
      healthcare disciplines. PARTICIPANTS: A total of 64 healthcare professionals and
      academics from all states and territories of Australia, and multiple healthcare
      disciplines were recruited. ETHICAL CONSIDERATIONS: Institutional ethics approval
      was obtained for data collection. Participants gave informed consent. All data
      were de-identified to protect participant anonymity. FINDINGS: Qualitative
      analysis indicated that Australian healthcare professionals often take more
      action in their personal than professional lives to protect the environment,
      particularly those with strong professional identities. The healthcare sector's
      focus on economic rationalism was a substantial barrier to environmentally
      responsible behaviour. Professionals also feared conflict and professional
      ostracism, and often did not feel qualified to take action. This led to
      healthcare professionals making inconsistent moral judgements, and feeling
      silenced and powerless. Constraints on non-clinical employees within and beyond
      the sector exacerbated these difficulties. DISCUSSION: The findings are
      consistent with the literature reporting that organisational constraints, and
      strong social identification, can inhibit actions that align with personal
      values. This disparity can cause moral distress and residue, leading to feelings
      of powerlessness, resulting in less ethical behaviour. CONCLUSION: The data
      highlight a disparity between personal and professional actions to address
      environmental sustainability. Given the constraints Australian healthcare
      professionals encounter, they are unlikely to shift to environmentally
      responsible practice without support from institutions and professional
      associations. Professional development is required to support this endeavour. The
      poor transference of pro-ecological behaviour from one setting to another is
      likely to have international implications for healthcare practice.

PMID- 24106260
TI  - Narratives of aggressive care: Knowledge, time, and responsibility.
AB  - BACKGROUND: While witnessing and providing aggressive care have been identified
      as predominant sources of moral distress, little is known about what nurses
      "know" to be the "right thing to do" in these situations. RESEARCH OBJECTIVES:
      The purpose of this study was to explore what nurses' moral knowledge is in
      situations of perceived overly aggressive medical care. RESEARCH DESIGN: A
      critical narrative approach was used. PARTICIPANTS: A total of 15 graduate
      nursing students from various practice areas participated. FINDINGS: Four
      narrative types were identified, including "Wait and see: medical uncertainty,"
      "Deflected responsibilities to respond to dying, death, or futility," "Divergent
      understandings, responsibilities, and temporalities," and "Privileged medical
      understandings and responsibilities." DISCUSSION: The knowledge of differentially
      situated persons is acknowledged in dissimilar ways, the time required to
      determine that enough has been done is perceived differently, and how moral
      responsibilities are understood also varies. CONCLUSIONS: A better understanding
      of how social roles influence how time, knowledge, and responsibility are related
      to the provision of aggressive care is needed.

PMID- 24106261
TI  - Reflections on the ethical dilemmas involved in promoting self-management.
AB  - Due to their understanding of self-management, healthcare team members
      responsible for depressed older persons can experience an ethical dilemma. Each
      team member contributes important knowledge and experience pertaining to the
      management of depression, which should be reflected in the management plan. The
      aim of this study was to explore healthcare team members' reflections on the
      ethical dilemmas involved in promoting self-management among depressed older
      persons. A qualitative design was used and data were collected by means of focus
      group interviews. The results revealed one main theme: 'Lack of trust in the
      community health care system's commitment to bringing about effectiveness and
      change, based on three themes; 'Struggling to ensure the reliable transfer of
      information about depressed older persons to professionals and family members',
      'Balancing autonomy, care and dignity' and 'Differences in the understanding of
      responsibility'. Lack of engagement on the part of and trust between the various
      professional categories who work in the community are extremely counterproductive
      and have serious implications for patient dignity as well as safety. In
      conclusion, ethical dilemmas occur when staff members are unable to act in
      accordance with their professional ethical stance and deliver an appropriate
      standard of care.

PMID- 24106262
TI  - Coercion in a locked psychiatric ward: Perspectives of patients and staff.
AB  - BACKGROUND: In spite of a national strategy for reducing coercion in the mental
      health services, Norway still has a high rate of involuntary treatment compared
      to other European countries. It is therefore crucial to study various parties
      involved in involuntary treatment in order to reduce coercion. RESEARCH QUESTION:
      How do patients and staff in a Norwegian locked psychiatric ward experience
      coercion? RESEARCH DESIGN: Participant observation and interviews. PARTICIPANTS:
      A total of 12 patients and 22 employees participated in this study. ETHICAL
      CONSIDERATIONS: This study is accepted by the National Committee for Medical
      Health Research Ethics. FINDINGS: The participants experienced coercion in
      different ways. Patients often felt inferior, while many of the staff felt guilty
      for violating patients' dignity, although they ascribed responsibility for their
      actions to the "system." The main themes are (1) corrections and house rules, (2)
      coercion is perceived as necessary, (3) the significance of material
      surroundings, and (4) being treated as a human being. DISCUSSION: The discussion
      draws upon the concepts of vulnerability, guilty conscience, and ethical
      sensitivity, related to the staffs' divergent views on coercion. CONCLUSION:
      Especially among staff, there are divergent views of coercion. Professionals
      being physically and emotionally close to the patient are more likely to
      understand him or her as a unique person with individual needs. If patients are
      kept at a distance, professionals as a group change to understand patients as
      members of a group with common needs and common restrictions.

PMID- 24106263
TI  - Aerodynamic implications of gull's drooped wing-tips.
AB  - When in gliding flight, gulls are observed to adopt a drooped wing-tip
      configuration. This paper investigates whether this configuration might represent
      an aerodynamic optimum or if it is the result of constraints imposed by the
      gull's anatomy. A computational model was developed for the aerodynamic
      performance of a gull in gliding flight. This model was used in conjunction with
      both global and local optimizers to determine the most aerodynamically optimal
      configuration for cases where the gull was constrained to move its wing within
      its natural flapping cycle as well as when the wing had full freedom of motion.
      The results of this analysis determined the best wing configuration for a gull in
      gliding flight and demonstrated that such a configuration not only had the
      highest lift-to-drag ratio but also could be achieved within the constraints of
      the kinematics of the gull wing. These results are of interest outside studies of
      gulls, since the drooped wing-tip configuration could be relevant for new designs
      of small air vehicles. 

PMID- 24106264
TI  - IA channels: diverse regulatory mechanisms.
AB  - In many peripheral and central neurons, A-type K(+) currents, IA, have been
      identified and shown to be key determinants in shaping action potential waveforms
      and repetitive firing properties, as well as in the regulation of synaptic
      transmission and synaptic plasticity. The functional properties and physiological
      roles of native neuronal IA, however, have been shown to be quite diverse in
      different types of neurons. Accumulating evidence suggests that this functional
      diversity is generated by multiple mechanisms, including the expression and
      subcellular distributions of IA channels encoded by different voltage-gated K(+)
      (Kv) channel pore-forming (alpha) subunits, interactions of Kv alpha subunits
      with cytosolic and/or transmembrane accessory subunits and regulatory proteins
      and post-translational modifications of channel subunits. Several recent reports
      further suggest that local protein translation in the dendrites of neurons and
      interactions between IA channels with other types of voltage-gated ion channels
      further expands the functional diversity of native neuronal IA channels. Here, we
      review the diverse molecular mechanisms that have been shown or proposed to
      underlie the functional diversity of native neuronal IA channels. 

PMID- 24106265
TI  - Multiple roles for astrocytes as effectors of cytokines and inflammatory
      mediators.
AB  - Astrocytes are increasingly recognized as exerting complex functions essential
      for normal neural activity in the healthy central nervous system (CNS). Because
      astrocytes also respond to all forms of CNS injury or disease, there is growing
      interest in how reactive astrogliosis might alter astrocyte functions and thereby
      affect neural functions. Reactive astrogliosis is heterogeneous and regulated in
      a context specific manner by different molecular signals. Prominent among
      astrocyte signaling mechanisms is the ability to respond to, as well as to
      produce, many different cytokines and inflammatory mediators. These signaling
      mechanisms enable astrocytes to interact with diverse cell types in ways that may
      contribute to crosstalk between immune/inflammatory and neural systems.
      Consistent with this notion is the increasing evidence that cytokines and
      inflammatory mediators modulate astrocyte signaling not only to influence immune
      and inflammatory activities in the CNS, but also to influence synaptic and neural
      functions in ways that may affect complex behaviors such as sickness behavior,
      pain, appetite, sleep, and mood. 

PMID- 24106266
TI  - CaMKIIdelta-dependent inhibition of cAMP-response element-binding protein
      activity in vascular smooth muscle.
AB  - One transcription factor mediator of Ca(2+)-signals is cAMP response element
      binding protein (CREB). CREB expression and/or activity negatively correlates
      with vascular smooth muscle (VSM) cell proliferation and migration.
      Multifunctional Ca(2+)/calmodulin-dependent protein kinases, including CaMKII,
      have been demonstrated to regulate CREB activity through both positive and
      negative phosphorylation events in vitro, but the function of CaMKII as a
      proximal regulator of CREB in intact cell systems, including VSM, is not clear.
      In this study, we used gain- and loss-of-function approaches to determine the
      function of CaMKIIdelta in regulating CREB phosphorylation, localization, and
      activity in VSM. Overexpression of constitutively active CaMKIIdelta specifically
      increased CREB phosphorylation on Ser(142) and silencing CaMKIIdelta expression
      by siRNA or blocking endogenous CaMKII activity with KN93 abolished thrombin- or
      ionomycin-induced CREB phosphorylation on Ser(142) without affecting Ser(133)
      phosphorylation. CREB-Ser(142) phosphorylation correlated with transient
      nucleocytoplasmic translocation of CREB. Thrombin-induced CREB promoter activity,
      CREB binding to Sik1 and Rgs2 promoters, and Sik1/Rgs2 transcription were
      enhanced by a kinase-negative CaMKIIdelta2 (K43A) mutant and inhibited by a
      constitutively active (T287D) mutant. Taken together, these studies establish
      negative regulation of CREB activity by endogenous CaMKIIdelta-dependent CREB
      Ser(142) phosphorylation and suggest a potential mechanism for CaMKIIdelta/CREB
      signaling in modulating proliferation and migration in VSM cells. 

PMID- 24106267
TI  - Phosphorylation of angiomotin by Lats1/2 kinases inhibits F-actin binding, cell
      migration, and angiogenesis.
AB  - The Hippo tumor suppressor pathway plays important roles in organ size control
      through Lats1/2 mediated phosphorylation of the YAP/TAZ transcription co
      activators. However, YAP/TAZ independent functions of the Hippo pathway are
      largely unknown. Here we report a novel role of the Hippo pathway in
      angiogenesis. Angiomotin p130 isoform (AMOTp130) is phosphorylated on a conserved
      HXRXXS motif by Lats1/2 downstream of GPCR signaling. Phosphorylation disrupts
      AMOT interaction with F-actin and correlates with reduced F-actin stress fibers
      and focal adhesions. Furthermore, phosphorylation of AMOT by Lats1/2 inhibits
      endothelial cell migration in vitro and angiogenesis in zebrafish embryos in
      vivo. Thus AMOT is a direct substrate of Lats1/2 mediating functions of the Hippo
      pathway in endothelial cell migration and angiogenesis. 

PMID- 24106268
TI  - Histone demethylase Jmjd3 regulates osteoblast differentiation via transcription
      factors Runx2 and osterix.
AB  - Post-translational modifications of histones including methylation play important
      roles in cell differentiation. Jumonji domain-containing 3 (Jmjd3) is a histone
      demethylase, which specifically catalyzes the removal of trimethylation of
      histone H3 at lysine 27 (H3K27me3). In this study, we examined the expression of
      Jmjd3 in osteoblasts and its roles in osteoblast differentiation. Jmjd3
      expression in the nucleus was induced in response to the stimulation of
      osteoblast differentiation as well as treatment of bone morphogenetic protein-2
      (BMP-2). Either treatment with Noggin, an inhibitor of BMP-2, or silencing of
      Smad1/5 suppressed Jmjd3 expression during osteoblast differentiation. Silencing
      of Jmjd3 expression suppressed osteoblast differentiation through the expression
      of bone-related genes including Runx2, osterix, osteopontin, bone sialoprotein
      (BSP), and osteocalcin (OCN). Silencing of Jmjd3 decreased the promoter
      activities of Runx2 and osterix and increased the level of H3K27me3 on the
      promoter regions of Runx2 and osterix. Introduction of the exogenous Runx2 and
      osterix partly rescued osteoblast differentiation in the shJmjd3 cells. The
      present results indicate that Jmjd3 plays important roles in osteoblast
      differentiation and regulates the expressions of BSP and OCN via transcription
      factors Runx2 and osterix. 

PMID- 24106269
TI  - RhoG protein regulates glycoprotein VI-Fc receptor gamma-chain complex-mediated
      platelet activation and thrombus formation.
AB  - We investigated the mechanism of activation and functional role of a hitherto
      uncharacterized signaling molecule, RhoG, in platelets. We demonstrate for the
      first time the expression and activation of RhoG in platelets. Platelet
      aggregation, integrin alphaIIbbeta3 activation, and alpha-granule and dense
      granule secretion in response to the glycoprotein VI (GPVI) agonists collagen
      related peptide (CRP) and convulxin were significantly inhibited in RhoG
      deficient platelets. In contrast, 2-MeSADP- and AYPGKF-induced platelet
      aggregation and secretion were minimally affected in RhoG-deficient platelets,
      indicating that the function of RhoG in platelets is GPVI-specific. CRP-induced
      phosphorylation of Syk, Akt, and ERK, but not SFK (Src family kinase), was
      significantly reduced in RhoG-deficient platelets. CRP-induced RhoG activation
      was consistently abolished by a pan-SFK inhibitor but not by Syk or PI3K
      inhibitors. Interestingly, unlike CRP, platelet aggregation and Syk
      phosphorylation induced by fucoidan, a CLEC-2 agonist, were unaffected in RhoG
      deficient platelets. Finally, RhoG(-/-) mice had a significant delay in time to
      thrombotic occlusion in cremaster arterioles compared with wild-type littermates,
      indicating the important in vivo functional role of RhoG in platelets. Our data
      demonstrate that RhoG is expressed and activated in platelets, plays an important
      role in GPVI-Fc receptor gamma-chain complex-mediated platelet activation, and is
      critical for thrombus formation in vivo. 

PMID- 24106270
TI  - RhoG protein regulates platelet granule secretion and thrombus formation in mice.
AB  - Rho GTPases such as Rac, RhoA, and Cdc42 are vital for normal platelet function,
      but the role of RhoG in platelets has not been studied. In other cells, RhoG
      orchestrates processes integral to platelet function, including actin
      cytoskeletal rearrangement and membrane trafficking. We therefore hypothesized
      that RhoG would play a critical role in platelets. Here, we show that RhoG is
      expressed in human and mouse platelets and is activated by both collagen-related
      peptide (CRP) and thrombin stimulation. We used RhoG(-/-) mice to study the
      function of RhoG in platelets. Integrin activation and aggregation were reduced
      in RhoG(-/-) platelets stimulated by CRP, but responses to thrombin were normal.
      The central defect in RhoG(-/-) platelets was reduced secretion from alpha
      granules, dense granules, and lysosomes following CRP stimulation. The integrin
      activation and aggregation defects could be rescued by ADP co-stimulation,
      indicating that they are a consequence of diminished dense granule secretion.
      Defective dense granule secretion in RhoG(-/-) platelets limited recruitment of
      additional platelets to growing thrombi in flowing blood in vitro and translated
      into reduced thrombus formation in vivo. Interestingly, tail bleeding times were
      normal in RhoG(-/-) mice, suggesting that the functions of RhoG in platelets are
      particularly relevant to thrombotic disorders. 

PMID- 24106271
TI  - Directed evolution of an angiopoietin-2 ligand trap by somatic hypermutation and
      cell surface display.
AB  - Tie2 is a receptor tyrosine kinase that is essential for the development and
      maintenance of blood vessels through binding the soluble ligands angiopoietin 1
      (Ang1) and 2 (Ang2). Ang1 is constitutively produced by perivascular cells and is
      protective of the adult vasculature. Ang2 plays an important role in blood vessel
      formation and is normally expressed during development. However, its re
      expression in disease states, including cancer and sepsis, results in
      destabilization of blood vessels contributing to the pathology of these
      conditions. Ang2 is thus an attractive therapeutic target. Here we report the
      directed evolution of a ligand trap for Ang2 by harnessing the B cell somatic
      hypermutation machinery and coupling this to selectable cell surface display of a
      Tie2 ectodomain. Directed evolution produced an unexpected combination of
      mutations resulting in loss of Ang1 binding but maintenance of Ang2 binding. A
      soluble form of the evolved ectodomain binds Ang2 but not Ang1. Furthermore, the
      soluble evolved ectodomain blocks Ang2 effects on endothelial cells without
      interfering with Ang1 activity. Our study has created a novel Ang2 ligand trap
      and provided proof of concept for combining surface display and exogenous gene
      diversification in B cells for evolution of a non-immunoglobulin target. 

PMID- 24106272
TI  - Early growth response-1 (EGR-1) and nuclear factor of activated T cells (NFAT)
      cooperate to mediate CD40L expression in megakaryocytes and platelets.
AB  - Increasing evidence implicates circulating platelets as mediators of chronic
      inflammatory and autoimmune diseases via the expression and release of CD40L, an
      important modulator of inflammation and adaptive immune responses traditionally
      associated with activated T cells. Emerging evidence suggests that platelet CD40L
      is dynamically regulated in several chronic inflammatory and autoimmune diseases
      and may mediate progression and secondary pathology associated with those disease
      states. The present study identifies NFATc2 as a key transcriptional modulator of
      CD40L expression in megakaryocytes and inflammatory activity of platelets.
      Furthermore, the current data show that EGR-1, a member of the early growth
      response family of zinc finger transcription factors, modulates NFATc2-dependent
      regulation of CD40L expression in megakaryocytes. Our novel demonstration that in
      vivo biochemical or genetic inhibition of NFATc2 activity in megakaryocyte
      diminishes platelet CD40L implicates the NFATc2/EGR-1 axis as a key regulatory
      pathway of inflammatory and immunomodulatory activity in platelets and represents
      a target for the development of therapeutics for the potential treatment of
      chronic inflammatory and autoimmune diseases. 

PMID- 24106273
TI  - Improving antigenic peptide vaccines for cancer immunotherapy using a dominant
      tumor-specific T cell receptor.
AB  - Vaccines that incorporate peptide mimics of tumor antigens, or mimotope vaccines,
      are commonly used in cancer immunotherapy and function by eliciting increased
      numbers of T cells that cross-react with the native tumor antigen. Unfortunately,
      they often elicit T cells that do not cross-react with or that have low affinity
      for the tumor antigen. Using a high affinity tumor-specific T cell clone, we
      identified a panel of mimotope vaccines for the dominant peptide antigen from a
      mouse colon tumor that elicits a range of tumor protection following vaccination.
      The TCR from this high affinity T cell clone was rarely identified in ex vivo
      evaluation of tumor-specific T cells elicited by mimotope vaccination.
      Conversely, a low affinity clone found in the tumor and following immunization
      was frequently identified. Using peptide libraries, we determined if this
      frequently identified TCR improved the discovery of efficacious mimotopes. We
      demonstrated that the representative TCR identified more protective mimotopes
      than the high affinity TCR. These results suggest that targeting a dominant
      fraction of tumor-specific T cells generates potent immunity and that
      consideration of the available T cell repertoire is necessary for targeted T cell
      therapy. These results have important implications when optimizing mimotope
      vaccines for cancer immunotherapy. 

PMID- 24106274
TI  - Ubiquitination regulates the neuroprotective function of the deubiquitinase
      ataxin-3 in vivo.
AB  - Deubiquitinases (DUBs) are proteases that regulate various cellular processes by
      controlling protein ubiquitination. Cell-based studies indicate that the
      regulation of the activity of DUBs is important for homeostasis and is achieved
      by multiple mechanisms, including through their own ubiquitination. However, the
      physiological significance of the ubiquitination of DUBs to their functions in
      vivo is unclear. Here, we report that ubiquitination of the DUB ataxin-3 at
      lysine residue 117, which markedly enhances its protease activity in vitro, is
      critical for its ability to suppress toxic protein-dependent degeneration in
      Drosophila melanogaster. Compared with ataxin-3 with only Lys-117 present, ataxin
      3 that does not become ubiquitinated performs significantly less efficiently in
      suppressing or delaying the onset of toxic protein-dependent degeneration in
      flies. According to further studies, the C terminus of Hsc70-interacting protein
      (CHIP), an E3 ubiquitin ligase that ubiquitinates ataxin-3 in vitro, is
      dispensable for its ubiquitination in vivo and is not required for the
      neuroprotective function of this DUB in Drosophila. Our work also suggests that
      ataxin-3 suppresses degeneration by regulating toxic protein aggregation rather
      than stability. 

PMID- 24106275
TI  - Retinitis pigmentosa mutants provide insight into the role of the N-terminal cap
      in rhodopsin folding, structure, and function.
AB  - Autosomal dominant retinitis pigmentosa (ADRP) mutants (T4K, N15S, T17M, V20G,
      P23A/H/L, and Q28H) in the N-terminal cap of rhodopsin misfold when expressed in
      mammalian cells. To gain insight into the causes of misfolding and to define the
      contributions of specific residues to receptor stability and function, we
      evaluated the responses of these mutants to 11-cis-retinal pharmacological
      chaperone rescue or disulfide bond-mediated repair. Pharmacological rescue
      restored folding in all mutants, but the purified mutant pigments in all cases
      were thermo-unstable and exhibited abnormal photobleaching, metarhodopsin II
      decay, and G protein activation. As a complementary approach, we superimposed
      this panel of ADRP mutants onto a rhodopsin background containing a juxtaposed
      cysteine pair (N2C/D282C) that forms a disulfide bond. This approach restored
      folding in T4K, N15S, V20G, P23A, and Q28H but not T17M, P23H, or P23L. ADRP
      mutant pigments obtained by disulfide bond repair exhibited enhanced stability,
      and some also displayed markedly improved photobleaching and signal transduction
      properties. Our major conclusion is that the N-terminal cap stabilizes opsin
      during biosynthesis and contributes to the dark-state stability of rhodopsin.
      Comparison of these two restorative approaches revealed that the correct position
      of the cap relative to the extracellular loops is also required for optimal
      photochemistry and efficient G protein activation. 

PMID- 24106276
TI  - Transforming growth factor-beta1 inhibits trophoblast cell invasion by inducing
      Snail-mediated down-regulation of vascular endothelial-cadherin protein.
AB  - Human trophoblast cells express transforming growth factor-beta (TGF-beta) and
      TGF-beta receptors. It has been shown that TGF-beta1 treatment decreases the
      invasiveness of trophoblast cells. However, the molecular mechanisms underlying
      TGF-beta1-decreased trophoblast invasion are still not fully understood. In the
      current study, we demonstrated that treatment of HTR-8/SVneo human trophoblast
      cells with TGF-beta1 decreased cell invasion and down-regulated the expression of
      vascular endothelial cadherin (VE-cadherin). In addition, the inhibitory effect
      of TGF-beta1 on VE-cadherin was confirmed in primary cultures of human
      trophoblast cells. Moreover, knockdown of VE-cadherin using siRNA decreased the
      invasiveness of HTR-8/SVneo cells and primary cultures of trophoblast cells.
      Treatment with TGF-beta1 induced the activation of Smad-dependent signaling
      pathways and the expression of Snail and Slug. Knockdown of Smads attenuated TGF
      beta1-induced up-regulation of Snail and Slug and down-regulation of VE-cadherin.
      Interestingly, depletion of Snail, but not Slug, attenuated TGF-beta1-induced
      down-regulation of VE-cadherin. Furthermore, overexpression of Snail suppressed
      VE-cadherin expression. Chromatin immunoprecipitation analyses showed the direct
      binding of Snail to the VE-cadherin promoter. These results provide evidence that
      Snail mediates TGF-beta1-induced down-regulation of VE-cadherin, which
      subsequently contributed to TGF-beta1-decreased trophoblast cell invasion. 

PMID- 24106277
TI  - Identification of a receptor for neuropeptide VGF and its role in neuropathic
      pain.
AB  - VGF (nonacronymic) is a neuropeptide precursor that plays multiple roles in
      regulation of energy balance, reproduction, hippocampal synaptic plasticity, and
      pain. Data from a number of pain models showed significant up-regulation of VGF
      in sensory neurons. TLQP-21, one of the VGF-derived neuropeptides, has been shown
      to induce a hyperalgesic response when injected subcutaneously into the hind paw
      of mice. However, the precise role of VGF-derived neuropeptides in neuropathic
      pain and the molecular identity of the receptor for VGF-derived peptides are yet
      to be investigated. Here we identified gC1qR, the globular heads of the C1q
      receptor, as the receptor for TLQP-21 using chemical cross-linking combined with
      mass spectrometry analysis. TLQP-21 caused an increase in intracellular Ca(2+)
      levels in rat macrophages and microglia. Inoculation of TLQP-21-stimulated
      macrophages into rat hind paw caused mechanical hypersensitivity. The increase in
      intracellular Ca(2+) levels in macrophages was attenuated by either siRNA or
      neutralizing antibodies against gC1qR. Furthermore, application of the gC1qR
      neutralizing antibody to rats with partial sciatic nerve ligation resulted in a
      delayed onset of nerve injury-associated mechanical hypersensitivity. These
      results indicate that gC1qR is the receptor for TLQP-21 and plays an important
      role in chronic pain through activation of macrophages. Because direct
      association between TLQP-21 and gC1qR is required for activation of macrophages
      and causes hypersensitivity, disrupting this interaction may be a useful new
      approach to develop novel analgesics. 

PMID- 24106278
TI  - Akt1 mediates alpha-smooth muscle actin expression and myofibroblast
      differentiation via myocardin and serum response factor.
AB  - Myofibroblast (MF) differentiation, marked by the de novo expression of smooth
      muscle alpha-actin (alphaSMA) stress fibers, plays a central role in wound
      healing and its persistence is a hallmark of fibrotic diseases. We have
      previously shown that Akt1 is necessary for wound healing through matrix
      regulation. However, the role of Akt1 in regulating MF differentiation with
      implications in fibrosis remains poorly defined. Here, we show that sustained
      activation of Akt1 was associated with a 6-fold increase in alphaSMA expression
      and assembly; an effect that is blunted in cells expressing inactive Akt1 despite
      TGFbeta stimulation. Mechanistically, Akt1 mediated TGFbeta-induced alphaSMA
      synthesis through the contractile gene transcription factors myocardin and serum
      response factor (SRF), independent of mammalian target of rapamycin in mouse
      embryonic fibroblasts and fibroblasts overexpressing active Akt1. Akt1 deficiency
      was associated with decreased myocardin, SRF, and alphaSMA expressions in vivo.
      Furthermore, sustained Akt1-induced alphaSMA synthesis markedly decreased upon
      RNA silencing of SRF and myocardin. In addition to its integral role in alphaSMA
      synthesis, we also show that Akt1 mediates fibronectin splice variant expression,
      which is required for MF differentiation, as well as total fibronectin, which
      generates the contractile force that promotes MF differentiation. In summary, our
      results constitute evidence that sustained Akt1 activation is crucial for TGFbeta
      induced MF formation and persistent differentiation. These findings highlight
      Akt1 as a novel potential therapeutic target for fibrotic diseases. 

PMID- 24106279
TI  - Structures of the substrate-free and product-bound forms of HmuO, a heme
      oxygenase from corynebacterium diphtheriae: x-ray crystallography and molecular
      dynamics investigation.
AB  - Heme oxygenase catalyzes the degradation of heme to biliverdin, iron, and carbon
      monoxide. Here, we present crystal structures of the substrate-free, Fe(3+)
      biliverdin-bound, and biliverdin-bound forms of HmuO, a heme oxygenase from
      Corynebacterium diphtheriae, refined to 1.80, 1.90, and 1.85 A resolution,
      respectively. In the substrate-free structure, the proximal and distal helices,
      which tightly bracket the substrate heme in the substrate-bound heme complex,
      move apart, and the proximal helix is partially unwound. These features are
      supported by the molecular dynamic simulations. The structure implies that the
      heme binding fixes the enzyme active site structure, including the water hydrogen
      bond network critical for heme degradation. The biliverdin groups assume the
      helical conformation and are located in the heme pocket in the crystal structures
      of the Fe(3+)-biliverdin-bound and the biliverdin-bound HmuO, prepared by in situ
      heme oxygenase reaction from the heme complex crystals. The proximal His serves
      as the Fe(3+)-biliverdin axial ligand in the former complex and forms a hydrogen
      bond through a bridging water molecule with the biliverdin pyrrole nitrogen atoms
      in the latter complex. In both structures, salt bridges between one of the
      biliverdin propionate groups and the Arg and Lys residues further stabilize
      biliverdin at the HmuO heme pocket. Additionally, the crystal structure of a
      mixture of two intermediates between the Fe(3+)-biliverdin and biliverdin
      complexes has been determined at 1.70 A resolution, implying a possible route for
      iron exit. 

PMID- 24106280
TI  - Agonist-induced Ca2+ sensitization in smooth muscle: redundancy of Rho guanine
      nucleotide exchange factors (RhoGEFs) and response kinetics, a caged compound
      study.
AB  - Many agonists, acting through G-protein-coupled receptors and Galpha subunits of
      the heterotrimeric G-proteins, induce contraction of smooth muscle through an
      increase of [Ca(2+)]i as well as activation of the RhoA/RhoA-activated kinase
      pathway that amplifies the contractile force, a phenomenon known as Ca(2+)
      sensitization. Galpha12/13 subunits are known to activate the regulator of G
      protein signaling-like family of guanine nucleotide exchange factors (RhoGEFs),
      which includes PDZ-RhoGEF (PRG) and leukemia-associated RhoGEF (LARG). However,
      their contributions to Ca(2+)-sensitized force are not well understood. Using
      permeabilized blood vessels from PRG(-/-) mice and a new method to silence LARG
      in organ-cultured blood vessels, we show that both RhoGEFs are activated by the
      physiologically and pathophysiologically important thromboxane A2 and endothelin
      1 receptors. The co-activation is the result of direct and independent activation
      of both RhoGEFs as well as their co-recruitment due to heterodimerization. The
      isolated recombinant C-terminal domain of PRG, which is responsible for
      heterodimerization with LARG, strongly inhibited Ca(2+)-sensitized force. We used
      photolysis of caged phenylephrine, caged guanosine 5'-O-(thiotriphosphate)
      (GTPgammaS) in solution, and caged GTPgammaS or caged GTP loaded on the
      RhoA.RhoGDI complex to show that the recruitment and activation of RhoGEFs is the
      cause of a significant time lag between the initial Ca(2+) transient and phasic
      force components and the onset of Ca(2+)-sensitized force. 

PMID- 24106282
TI  - Cross-ethnic meta-analysis of genetic variants for polycystic ovary syndrome.
AB  - CONTEXT: Genome-wide association studies (GWAS) have revealed new susceptibility
      loci for Chinese patients with polycystic ovary syndrome (PCOS). Because ethnic
      background adds to phenotypic diversities in PCOS, it seems plausible that
      genetic variants associated with PCOS act differently in various ethnic
      populations. OBJECTIVE: We studied cross-ethnic effects of Chinese PCOS loci (ie,
      LHCGR, THADA, DENND1A, FSHR, c9orf3, YAP1, RAB5B/SUOX, HMGA2, TOX3, INSR,
      SUMO1P1) in patients of Northern European descent. DESIGN: This study was a
      genetic association study conducted at an University Medical Center. PATIENTS:
      Association was studied in 703 Dutch PCOS patients and 2164 Dutch controls. To
      assess the cross-ethnic effect, we performed a meta-analysis of the Dutch data
      combined with results of previously published studies in PCOS patients from China
      (n = 2254) and the United States (n = 2618). Adjusted for multiple testing, a P
      value <3.1 * 10-3 was considered statistically significant. RESULTS: Meta
      analysis of the Chinese, US, and Dutch data resulted in 12 significant variants
      mapping to the YAP1 (P value = 1.0 * 10-9), RAB5B/SUOX (P value = 3.8 * 10-11),
      LHCGR (P value = 4.1 * 10-4), THADA (P value = 2.2 * 10-4 and P value = 1.3 * 10
      3), DENND1A (P value = 2.3 * 10-3 and P value = 2.5 * 10-3), FSHR (P value = 3.8
      * 10-5 and P value = 3.6 * 10-4), c9orf3 (P value = 2.0 * 10-6 and P value = 9.2
      * 10-6), SUMO1P1 (P value = 2.3 * 10-3) loci with odds ratios ranging from 1.19
      to 1.45 and 0.79 to 0.87. CONCLUSIONS: Overall, we observed for 12 of 17 genetic
      variants mapping to the Chinese PCOS loci similar effect size and identical
      direction in PCOS patients from Northern European ancestry, indicating a common
      genetic risk profile for PCOS across populations. Therefore, it is expected that
      large GWAS in PCOS patients from Northern European ancestry will partly identify
      similar loci as the GWAS in Chinese PCOS patients.

PMID- 24106281
TI  - Two carotenoid oxygenases contribute to mammalian provitamin A metabolism.
AB  - Mammalian genomes encode two provitamin A-converting enzymes as follows: the beta
      carotene-15,15'-oxygenase (BCO1) and the beta-carotene-9',10'-oxygenase (BCO2).
      Symmetric cleavage by BCO1 yields retinoids (beta-15'-apocarotenoids, C20),
      whereas eccentric cleavage by BCO2 produces long-chain (>C20) apocarotenoids.
      Here, we used genetic and biochemical approaches to clarify the contribution of
      these enzymes to provitamin A metabolism. We subjected wild type, Bco1(-/-),
      Bco2(-/-), and Bco1(-/-)Bco2(-/-) double knock-out mice to a controlled diet
      providing beta-carotene as the sole source for apocarotenoid production. This
      study revealed that BCO1 is critical for retinoid homeostasis. Genetic disruption
      of BCO1 resulted in beta-carotene accumulation and vitamin A deficiency
      accompanied by a BCO2-dependent production of minor amounts of beta-apo-10'
      carotenol (APO10ol). We found that APO10ol can be esterified and transported by
      the same proteins as vitamin A but with a lower affinity and slower reaction
      kinetics. In wild type mice, APO10ol was converted to retinoids by BCO1. We also
      show that a stepwise cleavage by BCO2 and BCO1 with APO10ol as an intermediate
      could provide a mechanism to tailor asymmetric carotenoids such as beta
      cryptoxanthin for vitamin A production. In conclusion, our study provides
      evidence that mammals employ both carotenoid oxygenases to synthesize retinoids
      from provitamin A carotenoids. 

PMID- 24106284
TI  - Despite a high prevalence of menstrual disorders, bone health is improved at a
      weight-bearing bone site in world-class female rhythmic gymnasts.
AB  - CONTEXT: Regular physical activity during puberty improves bone mass acquisition.
      However, it is unknown whether extreme intense training has the same favorable
      effect on the skeleton. OBJECTIVE: We evaluated the bone mass acquisition in a
      unique cohort of world-class rhythmic gymnasts. STUDY PARTICIPANTS: A total of
      133 adolescent girls and young women with a mean age of 18.7 +/- 2.7 (14.4-26.7)
      years participated in this study: 82 elite rhythmic gymnasts (RGs) and 51
      controls (CONs). MAIN OUTCOME MEASURES: Anthropometric variables and body
      composition were assessed, and all participants completed questionnaires on their
      general medical, menstrual, and training histories. Broadband ultrasound
      attenuation (BUA in decibels per megahertz) was determined by quantitative
      ultrasound at the heel. RESULTS: RGs presented lower weight (-8.5%, P < .001),
      body mass index (-11.7%, P < .001), and body fat mass (-43%, P < .001) and higher
      muscle mass (6.3%, P < .01) and height (+2.8 cm, P < .01). RGs presented an age
      of menarche significantly delayed compared with CONs (15.6 +/- 1.6 vs 12.7 +/-
      1.7 years; P < .001) and a high prevalence of menstrual disorders (64%). BUA
      values were higher in RGs vs CONs (68.6 +/- 4.6 and 65.4 +/- 3.3 dB/Mhz,
      respectively; P < .001). This difference was exacerbated when BUA was adjusted
      for age and body weight. BUA values in RGs were not affected by menstrual or
      training status. Among RGs with menarche, BUA was higher (71.5 +/- 4.1 and 67.9
      +/- 3.5 dB/Mhz) for delayed (14.4 +/- 0.8 years) vs severely delayed (17.3 +/-
      1.4 years) menarcheal age. BUA was positively correlated with body weight and
      body mass index and tended to be correlated with age. CONCLUSION: Conversely to
      expectations for adolescents and young women with a high prevalence of menstrual
      disorders and/or delayed menarche, intense training in rhythmic gymnastics
      appeared to have a beneficial effect on the bone health of a weight-bearing site.
      This effect was nevertheless modulated by the age of menarche. The high
      mechanical loading generated by this activity may counterbalance the negative
      effect of menstrual disorders.

PMID- 24106283
TI  - Clinical review: The role of the parent compound vitamin D with respect to
      metabolism and function: Why clinical dose intervals can affect clinical
      outcomes.
AB  - CONTEXT: There is no doubt that vitamin D must be activated to the hormonal form
      1,25-dihydroxyvitamin D to achieve full biological activity or that many tissues
      participate in this activation process-be it endocrine or autocrine. We believe
      that not only is 25-hydroxyvitamin D important to tissue delivery for this
      activation process, but also that intact vitamin D has a pivotal role in this
      process. OBJECTIVE: In this review, evidence on the vitamin D endocrine/autocrine
      system is presented and discussed in relation to vitamin D-binding protein
      affinity, circulating half-lives, and enzymatic transformations of vitamin D
      metabolites, and how these affect biological action in any given tissue.
      CONCLUSIONS: Circulating vitamin D, the parent compound, likely plays an
      important physiological role with respect to the vitamin D endocrine/autocrine
      system, as a substrate in many tissues, not originally thought to be important.
      Based on emerging data from the laboratory, clinical trials, and data on
      circulating 25-hydroxyvitamin D amassed during many decades, it is likely that
      for the optimal functioning of these systems, significant vitamin D should be
      available on a daily basis to ensure stable circulating concentrations, implying
      that variation in vitamin D dosing schedules could have profound effects on the
      outcomes of clinical trials because of the short circulating half-life of intact
      vitamin D.

PMID- 24106285
TI  - Decreased bone mineral density in subjects carrying familial defective
      apolipoprotein B-100.
AB  - CONTEXT: Although numerous epidemiologic studies have documented associations
      between osteoporosis and cardiovascular disease, the mechanisms underlying this
      association remain to be clarified. One hypothesis is that hyperlipidemia may be
      a common predisposing factor to both atherosclerotic heart disease and bone
      fragility. OBJECTIVE: To evaluate this, we compared bone mineral density (BMD)
      between subjects with and without the R3500Q APOB mutation, the cause of familial
      defective apolipoprotein B-100, which has been previously shown to markedly
      increase low-density lipoprotein cholesterol (LDL-C). We hypothesized that R3500Q
      carriers would have lower BMD due to lifetime, elevated LDL-C. DESIGN: This was a
      a cross-sectional study in the Old Order Amish (OOA) population. PARTICIPANTS:
      The R3500Q APOB mutation is present at a high frequency (~6% vs <0.5%) in the OOA
      population due to a founder effect. Therefore, we conducted analysis on 1097
      Amish individuals of whom 125 were R3500Q carriers. MAIN OUTCOME MEASURE: BMD was
      measured by dual-energy x-ray absorptiometry. RESULTS: After adjusting for age,
      age(2), sex, body mass index, and family structure, carriers for the Q risk
      allele had significantly lower BMD than noncarriers at the femoral neck (P =
      .037), lumbar spine (P = .035) and whole body (P = .016). Adjusting for LDL-C
      attenuated the association between R3500Q genotype and BMD but did not completely
      explain the relationship. Subgroup analyses showed no significant interactions
      with sex, age, or presence of metabolic syndrome. CONCLUSION: These results use
      the unique genetic architecture of the OOA population to provide a novel line of
      evidence supporting a causal role for elevated LDL-C in lowering BMD.

PMID- 24106286
TI  - Shikonin inhibits thyroid cancer cell growth and invasiveness through targeting
      major signaling pathways.
AB  - CONTEXT: Shikonin, which is an active naphthoquinone isolated from traditional
      Chinese herbal medicine Zi Cao, has been recently developed to use as an
      antitumor agent in colorectal cancer, melanoma, leukemia, breast cancer, and
      hepatocellular cancer. However, its antitumor effect in thyroid cancer remains
      largely unknown. OBJECTIVES: The aim of the study was to test the therapeutic
      potential of shikonin for thyroid cancer and explore the mechanisms underlying
      antitumor effects of shikonin. EXPERIMENTAL DESIGN: We examined the effects of
      shikonin on proliferation, cell cycle, apoptosis, migration, invasion, and
      xenograft tumor growth in thyroid cancer cells and the effect of shikonin on
      proliferation of primary thyroid cancer cells. RESULTS: Shikonin inhibited
      thyroid cancer cell proliferation in a dose- and time-dependent manner and
      induced cell cycle arrest. Moreover, shikonin induced cell apoptosis through
      reactive oxygen species-mediated DNA damage and activation of the p53 signaling
      pathway. Our data also showed that shikonin dramatically inhibited thyroid cancer
      cell migration and invasion by suppressing epithelial-mesenchymal transition and
      downregulating expression of Slug and MMP-2, -9, and -14. Further elucidation of
      the mechanisms involved revealed that shikonin markedly repressed the
      phosphorylation of Erk and Akt and activated the p16/Retinoblastoma protein (Rb)
      pathway in thyroid cancer cells. Growth of xenograft tumors derived from the
      thyroid cancer cell line FTC133 in nude mice was significantly inhibited by
      shikonin. Importantly, we did not find the effect of shikonin on liver function
      in mice. CONCLUSION: We for the first time demonstrated that shikonin is a
      potentially effective antitumor agent for thyroid cancers.

PMID- 24106287
TI  - Vitamin D deficiency in Serbian patients with Rett syndrome.
AB  - INTRODUCTION: Rett syndrome (RTT) is a severe neurodevelopmental disorder. Bone
      manifestations of RTT include osteopenia and fractures. Studies addressing serum
      vitamin D levels in patients with RTT are scarce. GOALS: The goals of this study
      were (1) to determine the prevalence of vitamin D deficiency in patients with
      RTT, (2) to compare serum vitamin D levels between patients with RTT and those
      with other neurological diseases, and (3) to explore the correlation between
      demographic and clinical characteristics of patients with RTT and vitamin D
      levels. METHODS: Demographic and clinical characteristics included age, body mass
      index Z-score, mutation status, clinical severity score, presence of epilepsy,
      number of antiepileptic drugs, history of fractures, scoliosis, and ambulation
      ability. Laboratory parameters included serum 25-hydroxyvitamin D [25(OH)D], PTH,
      calcium, and alkaline phosphatase. RESULTS: The study included 35 patients with
      RTT and 35 age-matched females with other neurological diseases. The median serum
      25(OH)D concentration in the RTT group was 26.25 nmol/L, with values <75 nmol/L
      in all participants. Severe deficiency (<25 nmol/L) was detected in 17 of 35
      (48.6%) patients. The median 25(OH)D concentration was significantly lower in
      patients with RTT than in control subjects. The risk for fracture by 12 years of
      age in patients with RTT was 35.3%. An inverse correlation of the 25(OH)D level
      to age and PTH level was detected. Patients receiving antiepileptic polytherapy
      had a 3.3 times greater chance for severe vitamin D deficiency than patients
      receiving monotherapy. CONCLUSION: The prevalence of vitamin D deficiency in
      patients with RTT is higher than that in patients with other neurological
      diseases. The high risk for vitamin D deficiency should be accounted for in the
      strategy of antiepileptic treatment in RTT, especially when polytherapy is
      considered.

PMID- 24106288
TI  - Serum 25-hydroxyvitamin D and incidence of fatal and nonfatal cardiovascular
      events: a prospective study with repeated measurements.
AB  - CONTEXT: Several studies suggested that low serum concentrations of 25
      hydroxyvitamin D (25(OH)D) are associated with an increased risk of
      cardiovascular disease (CVD). However, the evidence is still inconclusive, mostly
      based on CVD mortality and studies with single 25(OH)D measurements. OBJECTIVE:
      We aimed to assess the association of 25(OH)D with fatal and nonfatal CVD in the
      same study population, using repeated 25(OH)D measurements and competing risks
      analysis. DESIGN: This was a population-based cohort study (ESTHER study,
      baseline 2000-2002). Follow-up data, including survival status, were collected
      after 2, 5, and 8 years. The response rate for survival was 99.9%. SETTING:
      Participants were recruited during a health screening examination by their
      general practitioners. 25(OH)D was measured in blood samples collected at
      baseline and the 5-year follow-up visit. PATIENTS OR OTHER PARTICIPANTS: A total
      of 9949 men and women, aged 50 to 74 years at baseline, with sufficient knowledge
      of the German language and resident in the German state of Saarland were included
      in the study. MAIN OUTCOME MEASURES: Outcomes included CVD, coronary heart
      disease (CHD), and stroke, in total and differentiated into fatal and nonfatal
      events. RESULTS: Overall, 854 study participants had a nonfatal and 176 a fatal
      CVD event during 8 years of follow-up. Comparing subjects with 25(OH)D levels
      below 30 nmol/L and above 50 nmol/L resulted in a hazard ratio of 1.27 (95%
      confidence interval = 1.05-1.54) for total CVD and 1.62 (95% confidence interval
      = 1.07-2.48) for fatal CVD in a model adjusted for important potential
      confounders. No significant association for nonfatal CVD was observed. In dose
      response analysis, we observed an increased cardiovascular risk at 25(OH)D levels
      below 75 nmol/L. Results for CHD and stroke were comparable to the results
      obtained for the composite outcome CVD. CONCLUSIONS: Our results support evidence
      that low 25(OH)D levels are associated with moderately increased risk of CVD and
      indicate that the observed association is much stronger for fatal than for
      nonfatal events.

PMID- 24106289
TI  - Endothelial colony-forming cells derived from pregnancies complicated by
      intrauterine growth restriction are fewer and have reduced vasculogenic capacity.
AB  - CONTEXT: Endothelial colony-forming cells (ECFCs) are the only putative
      endothelial progenitor cells capable of vasculogenesis, and their dysfunction may
      represent a risk factor for cardiovascular disease. Intrauterine growth
      restriction (IUGR) is a pregnancy-related disorder associated with long-term
      cardiovascular risk. OBJECTIVE: Our objective was to determine whether ECFCs
      derived from pregnancies complicated by IUGR exhibit altered vasculogenic
      potential. DESIGN AND SETTING: This was a prospective cohort study; patients were
      recruited at St. Mary's Hospital, Manchester, United Kingdom. PARTICIPANTS:
      Twenty-three women with normal pregnancies and 13 women with IUGR-complicated
      pregnancies at gestational ages above 37 weeks were included. MAIN OUTCOME
      MEASURES: Vasculogenic capacity of rigorously characterized ECFCs was
      investigated in vivo by measuring blood vessel formation in collagen/fibronectin
      gels implanted in mice; proliferative, migratory, and chemotactic abilities were
      assessed in cell culture. Placental uptake of fetal ECFCs, assessed by
      differences in arterial and venous cord blood content, was determined by flow
      cytometry. RESULTS: In vivo, IUGR ECFCs formed fewer blood vessels (P < .001) and
      capillaries (P = .001) compared with normal pregnancy-derived ECFCs. In culture
      conditions, IUGR ECFCs had reduced proliferation (P = .01) and migration (P =
      .007) and diminished chemotactic abilities to stromal cell-derived factor 1 (P =
      .007) coupled with reduced hypoxia-induced matrix metalloproteinase-2 release (P
      = .02). Finally, in IUGR pregnancies, the number of ECFCs was lower in arterial
      cord blood (P = .002) and placental uptake of cells was reduced (P < .001).
      CONCLUSIONS: ECFCs derived from IUGR cord blood are rarefied and dysfunctional,
      resulting in diminished vasculogenic potential; this could be a cause of
      placental dysfunction in IUGR, with long-term postnatal implications for
      cardiovascular function in offspring.

PMID- 24106290
TI  - Phloem transport: a review of mechanisms and controls.
AB  - It is generally believed that an osmotically generated pressure gradient drives
      the phloem mass flow. So far, this widely accepted Munch theory has required
      remarkably few adaptations, but the debate on alternative and additional
      hypotheses is still ongoing. Recently, a possible shortcoming of the Munch theory
      has been pointed out, suggesting that the Munch pressure flow is more suitable
      for herbs than for trees. Estimation of the phloem resistance indicates that a
      point might be reached in long sieve tubes where the pressure required to drive
      the Munch flow cannot be generated. Therefore, the relay hypothesis regained
      belief as it implies that the sieve tubes are shorter then the plant's axial
      axis. In the source phloem, three different loading strategies exist which
      probably result from evolutionary advantages. Passive diffusion seems to be the
      most primitive one, whereas active loading strategies substantially increase the
      growth potential. Along the transport phloem, a leakage-retrieval mechanism is
      observed. Appreciable amounts of carbohydrates are lost from the sieve tubes to
      feed the lateral sinks, while a part of these lost carbohydrates is subsequently
      reloaded into the sieve tubes. This mechanism is probably involved to buffer
      short-term irregularities in phloem turgor and gradient. In the long term, the
      mechanism controls the replenishment and remobilization of lateral stem storage
      tissues. As phloem of higher plants has multiple functions in plant development,
      reproduction, signalling, and growth, the fundamental understanding of the
      mechanisms behind phloem transport should be elucidated to increase our ability
      to influence plant growth and development. 

PMID- 24106291
TI  - In vivo inhibition of cysteine proteases provides evidence for the involvement of
      'senescence-associated vacuoles' in chloroplast protein degradation during dark
      induced senescence of tobacco leaves.
AB  - Breakdown of leaf proteins, particularly chloroplast proteins, is a massive
      process in senescing leaves. In spite of its importance in internal N recycling,
      the mechanism(s) and the enzymes involved are largely unknown. Senescence
      associated vacuoles (SAVs) are small, acidic vacuoles with high cysteine
      peptidase activity. Chloroplast-targeted proteins re-localize to SAVs during
      senescence, suggesting that SAVs might be involved in chloroplast protein
      degradation. SAVs were undetectable in mature, non-senescent tobacco leaves.
      Their abundance, visualized either with the acidotropic marker Lysotracker Red or
      by green fluorescent protein (GFP) fluorescence in a line expressing the
      senescence-associated cysteine protease SAG12 fused to GFP, increased during
      senescence induction in darkness, and peaked after 2-4 d, when chloroplast
      dismantling was most intense. Increased abundance of SAVs correlated with higher
      levels of SAG12 mRNA. Activity labelling with a biotinylated derivative of the
      cysteine protease inhibitor E-64 was used to detect active cysteine proteases.
      The two apparently most abundant cysteine proteases of senescing leaves, of 40kDa
      and 33kDa were detected in isolated SAVs. Rubisco degradation in isolated SAVs
      was completely blocked by E-64. Treatment of leaf disks with E-64 in vivo
      substantially reduced degradation of Rubisco and leaf proteins. Overall, these
      results indicate that SAVs contain most of the cysteine protease activity of
      senescing cells, and that SAV cysteine proteases are at least partly responsible
      for the degradation of stromal proteins of the chloroplast. 

PMID- 24106292
TI  - New insights for estimating the genetic value of segregating apple progenies for
      irregular bearing during the first years of tree production.
AB  - Because irregular bearing generates major agronomic issues in fruit-tree species,
      particularly in apple, the selection of regular cultivars is desirable. Here, we
      aimed to define methods and descriptors allowing a diagnostic for bearing
      behaviour during the first years of tree maturity, when tree production is
      increasing. Flowering occurrences were collected at whole-tree and (annual) shoot
      scales on a segregating apple population. At both scales, the number of
      inflorescences over the years was modelled. Two descriptors were derived from
      model residuals: a new biennial bearing index, based on deviation around yield
      trend over years and an autoregressive coefficient, which represents dependency
      between consecutive yields. At the shoot scale, entropy was also considered to
      represent the within-tree flowering synchronicity. Clusters of genotypes with
      similar bearing behaviours were built. Both descriptors at the whole-tree and
      shoot scales were consistent for most genotypes and were used to discriminate
      regular from biennial and irregular genotypes. Quantitative trait loci were
      detected for the new biennial bearing index at both scales. Combining descriptors
      at a local scale with entropy showed that regular bearing at the tree scale may
      result from different strategies of synchronization in flowering at the local
      scale. The proposed methods and indices open an avenue to quantify bearing
      behaviour during the first years of tree maturity and to capture genetic
      variations. Their extension to other progenies and species, possible variants of
      descriptors, and their use in breeding programmes considering a limited number of
      years or fruit yields are discussed. 

PMID- 24106293
TI  - Novel clostridium botulinum toxin and dual use research of concern issues.

PMID- 24106294
TI  - Botulinum neurotoxins: more and more diverse and fascinating toxic proteins.

PMID- 24106295
TI  - Molecular characterization of a novel botulinum neurotoxin type H gene.
AB  - We sequenced the 2 botulinum toxin gene clusters of Clostridium botulinum strain
      IBCA10-7060 type Bh. The sequence of bont/H differed substantially from the
      sequences of the 7 known bont genes for toxin types A-G. The 5' one-third
      terminus of bont/H that codes for the botulinum toxin light chain differed
      markedly from the light chain coding sequences of toxin types A-G. The 3' two
      thirds terminus of bont/H that codes for the botulinum toxin heavy chain
      contained a novel Hn translocation domain coding sequence and a nonneutralizing
      type A-like Hc binding domain coding sequence. bont/H was part of an orfX toxin
      gene cluster that was located at a unique chromosomal site distant from those
      used by other botulinum toxin gene clusters. The bont/B sequence was similar to
      that of subtype bont/B2 and was located within its ha toxin gene cluster at the
      oppA/brnQ site. Our findings further establish that C. botulinum IBCA10-7060
      produces novel BoNT/H. 

PMID- 24106296
TI  - A novel strain of Clostridium botulinum that produces type B and type H botulinum
      toxins.
AB  - BACKGROUND: Clostridium botulinum strain IBCA10-7060, isolated from a patient
      with infant botulism, produced botulinum neurotoxin type B (BoNT/B) and another
      BoNT that, by use of the standard mouse bioassay, could not be neutralized by any
      of the Centers for Disease Control and Prevention-provided monovalent polyclonal
      botulinum antitoxins raised against BoNT types A-G. METHODS AND RESULTS:  The
      combining of antitoxins to neutralize the toxicity of known bivalent C. botulinum
      strains Ab, Ba, Af, and Bf also failed to neutralize the second BoNT. Analysis of
      culture filtrate by double immunodiffusion yielded a single line of
      immunoprecipitate with anti-A, anti-B, and anti-F botulinum antitoxins but not
      with anti-E antitoxin. A heptavalent F(ab')2 botulinum antitoxin A-G obtained
      from the US Army also did not neutralize the second BoNT. An antitoxin raised
      against IBCA10-7060 toxoid protected mice against BoNT/B (Okra) and against the
      second BoNT but did not protect mice against BoNT/A (Hall) or BoNT/F (Langeland).
      CONCLUSION: The second BoNT thus fulfilled classic criteria for being designated
      BoNT/H. IBCA10-7060 is the first C. botulinum type Bh strain to be identified.
      BoNT/H is the first new botulinum toxin type to be recognized in >40 years, and
      its recognition could not have been accomplished without the availability of the
      mouse bioassay.

PMID- 24106297
TI  - "Inconvenient truths" in the pursuit of scientific knowledge and public health.

PMID- 24106298
TI  - Clinical implications of CSN6 protein expression and correlation with mutant-type
      P53 protein in breast cancer.
AB  - OBJECTIVE: Constitutive photomorphogenesis 9 subunit 6, as one subunit of the
      constitutive photomorphogenesis 9, plays an important role in tumor development.
      The aim of the study was to investigate the clinical and prognostic implications
      of constitutive photomorphogenesis 9 subunit 6 protein in breast cancer. METHODS:
      We examined mastectomy specimens from 92 invasive breast cancers and matched with
      20 adjacent non-cancerous tissues using immunohistochemistry. RESULTS: The
      positive expressions of constitutive photomorphogenesis 9 subunit 6 protein in
      invasive breast cancer and adjacent non-cancerous tissue were 32.61% (30 of 92)
      and 10% (2 of 20), respectively. The positive expression of constitutive
      photomorphogenesis 9 subunit 6 protein was related to tumor size, histological
      type and lymph node metastasis (P = 0.015, 0.009 and 0.009, respectively). After
      univariate analysis, constitutive photomorphogenesis 9 subunit 6-positive
      expression was only found to be significantly related to mutant-type P53
      expression (P < 0.001). Spearman's correlation analysis was used to demonstrate
      negative correlations between constitutive photomorphogenesis 9 subunit 6 and
      mutant-type P53 (r = -0.417). Constitutive photomorphogenesis 9 subunit 6
      positive was associated with both poorer breast cancer-specific survival in 92
      cases and in the lymph node-positive group (P = 0.007 and 0.024, respectively).
      In the Cox regression test, constitutive photomorphogenesis 9 subunit 6 protein
      was not shown to be an independent prognostic factor for breast cancer.
      CONCLUSION: Constitutive photomorphogenesis 9 subunit 6 might be a new potential
      biomarker for breast cancer. However, the underlying mechanisms of constitutive
      photomorphogenesis 9 subunit 6's involvement are still unclear.

PMID- 24106299
TI  - Optogenetics.

PMID- 24106301
TI  - Finding trimeric HIV-1 envelope glycoproteins in random noise.

PMID- 24106302
TI  - Structure of trimeric HIV-1 envelope glycoproteins.

PMID- 24106304
TI  - Electrostatic origin of the unidirectionality of walking myosin V motors.
AB  - Understanding the basis for the action of myosin motors and related molecular
      machines requires a quantitative energy-based description of the overall
      functional cycle. Previous theoretical attempts to do so have provided
      interesting insights on parts of the cycle but could not generate a structure
      based free energy landscape for the complete cycle of myosin. In particular, a
      nonphenomenological structure/energy-based understanding of the unidirectional
      motion is still missing. Here we use a coarse-grained model of myosin V and
      generate a structure-based free energy surface of the largest conformational
      change, namely the transition from the post- to prepowerstroke movement. We also
      couple the observed energetics of ligand binding/hydrolysis and product release
      to that of the conformational surface and reproduce the energetics of the
      complete mechanochemical cycle. It is found that the release in electrostatic
      free energy upon changing the conformation of the lever arm and the convertor
      domain from its post- to prepowerstroke state provides the necessary energy to
      bias the system towards the unidirectional movement of myosin V on the actin
      filament. The free energy change of 11 kcal is also in the range of ~2-3 pN,
      which is consistent with the experimentally observed stalling force required to
      stop the motor completely on its track. The conformational-chemical coupling
      generating a successful powerstroke cycle is believed to be conserved among most
      members of the myosin family, thus highlighting the importance of the previously
      unknown role of electrostatics free energy in guiding the functional cycle in
      other actin-based myosin motors. 

PMID- 24106306
TI  - Avoiding the pitfalls of single particle cryo-electron microscopy: Einstein from
      noise.
AB  - Single particle cryo-electron microscopy is currently poised to produce high
      resolution structures of many biological assemblies, but several pitfalls can
      trap the unwary. This critique highlights one problem that is particularly
      relevant when smaller structures are being studied. It is known as "Einstein from
      noise," in which the experimenter honestly believes they have recorded images of
      their particles, whereas in reality, most if not all of their data consist of
      pure noise. Selection of particles using cross-correlation methods can then lead
      to 3D maps that resemble the model used in the initial selection and provide the
      illusion of progress. Suggestions are given about how to circumvent the problem. 

PMID- 24106303
TI  - De novo identification of VRC01 class HIV-1-neutralizing antibodies by next
      generation sequencing of B-cell transcripts.
AB  - Next-generation sequencing of antibody transcripts provides a wealth of data, but
      the ability to identify function-specific antibodies solely on the basis of
      sequence has remained elusive. We previously characterized the VRC01 class of
      antibodies, which target the CD4-binding site on gp120, appear in multiple
      donors, and broadly neutralize HIV-1. Antibodies of this class have developmental
      commonalities, but typically share only ~50% amino acid sequence identity among
      different donors. Here we apply next-generation sequencing to identify VRC01
      class antibodies in a new donor, C38, directly from B cell transcript sequences.
      We first tested a lineage rank approach, but this was unsuccessful, likely
      because VRC01 class antibody sequences were not highly prevalent in this donor.
      We next identified VRC01 class heavy chains through a phylogenetic analysis that
      included thousands of sequences from C38 and a few known VRC01 class sequences
      from other donors. This "cross-donor analysis" yielded heavy chains with little
      sequence homology to previously identified VRC01 class heavy chains. Nonetheless,
      when reconstituted with the light chain from VRC01, half of the heavy chain
      chimeric antibodies showed substantial neutralization potency and breadth. We
      then identified VRC01 class light chains through a five-amino-acid sequence motif
      necessary for VRC01 light chain recognition. From over a million light chain
      sequences, we identified 13 candidate VRC01 class members. Pairing of these light
      chains with the phylogenetically identified C38 heavy chains yielded functional
      antibodies that effectively neutralized HIV-1. Bioinformatics analysis can thus
      directly identify functional HIV-1-neutralizing antibodies of the VRC01 class
      from a sequenced antibody repertoire. 

PMID- 24106307
TI  - High-resolution restoration of 3D structures from widefield images with extreme
      low signal-to-noise-ratio.
AB  - Four-dimensional fluorescence microscopy--which records 3D image information as a
      function of time--provides an unbiased way of tracking dynamic behavior of
      subcellular components in living samples and capturing key events in complex
      macromolecular processes. Unfortunately, the combination of phototoxicity and
      photobleaching can severely limit the density or duration of sampling, thereby
      limiting the biological information that can be obtained. Although widefield
      microscopy provides a very light-efficient way of imaging, obtaining high-quality
      reconstructions requires deconvolution to remove optical aberrations.
      Unfortunately, most deconvolution methods perform very poorly at low signal-to
      noise ratios, thereby requiring moderate photon doses to obtain acceptable
      resolution. We present a unique deconvolution method that combines an entropy
      based regularization function with kernels that can exploit general spatial
      characteristics of the fluorescence image to push the required dose to extreme
      low levels, resulting in an enabling technology for high-resolution in vivo
      biological imaging.

PMID- 24106310
TI  - Disease modification in multiple sclerosis: an update.
AB  - Although there has been unequivocal progress in the development of treatments for
      multiple sclerosis over the last 20&emsp14;years, currently licensed treatments
      have demonstrated convincing effects on disease course only with reference to
      relapse frequency. This review summarises the progress made, highlights the
      indications for, and limitations of, current disease-modifying therapies and
      discusses some interventions currently in development. 

PMID- 24106309
TI  - Nonequilibrium dynamics of helix reorganization observed by transient 2D IR
      spectroscopy.
AB  - The relaxation of helical structures very close to equilibrium is observed via
      transient 2D IR spectroscopy. An initial distribution of synthetically distorted
      helices having an unnatural bridge linking the 10th and 12th residues of an
      alanine-rich alpha-helix is released to evolve into the equilibrium distribution
      of alpha-helix conformations. The bridge constrains the structure to be slightly
      displaced from the full alpha-helix equilibrium near these residues, yet the
      peptide is not unfolded completely. The release is accomplished by a
      subpicosecond pulse of UV irradiation. The resulting 2D IR signals are used to
      obtain snapshots of the ~100-ps helical conformational reorganization of the
      distorted dihedral angle and distance between amide units at chemical bond length
      scale resolution. The decay rates of the angle between the dipoles, dihedral
      angles, and distance autocorrelations obtained from molecular dynamics
      simulations support the experiments, providing evidence that the final helix
      collapse conforms to linear response theory. 

PMID- 24106308
TI  - Aryl hydrocarbon receptor deficiency causes dysregulated cellular matrix
      metabolism and age-related macular degeneration-like pathology.
AB  - The aryl hydrocarbon receptor (AhR) is a nuclear receptor that regulates
      xenobiotic metabolism and detoxification. Herein, we report a previously
      undescribed role for the AhR signaling pathway as an essential defense mechanism
      in the pathogenesis of early dry age-related macular degeneration (AMD), the
      leading cause of vision loss in the elderly. We found that AhR activity and
      protein levels in human retinal pigment epithelial (RPE) cells, cells vulnerable
      in AMD, decrease with age. This finding is significant given that age is the most
      established risk factor for development of AMD. Moreover, AhR(-/-) mice exhibit
      decreased visual function and develop dry AMD-like pathology, including disrupted
      RPE cell tight junctions, accumulation of RPE cell lipofuscin, basal laminar and
      linear-like deposit material, Bruch's membrane thickening, and progressive RPE
      and choroidal atrophy. High-serum low-density lipoprotein levels were also
      observed in AhR(-/-) mice. In its oxidized form, this lipoprotein can stimulate
      increased secretion of extracellular matrix molecules commonly found in deposits
      from RPE cells, in an AhR-dependent manner. This study demonstrates the
      importance of cellular clearance via the AhR signaling pathway in dry AMD
      pathogenesis, implicating AhR as a potential target, and the mouse model as a
      useful platform for validating future therapies. 

PMID- 24106311
TI  - From physician intent to the pharmacy label: prevalence and description of
      discrepancies from a cross-sectional evaluation of electronic prescriptions.
AB  - OBJECTIVE: The objectives of this cross-sectional study were to estimate the
      prevalence of unintended discrepancies between three sources of prescription
      information and to describe the types of electronic prescribing system
      vulnerabilities identified. METHODS: Staff from community pharmacies identified
      approximately 200 new prescriptions written at three participating ambulatory
      care clinics (2 adult, 1 paediatric). Unintended discrepancies were identified by
      comparing three sources of prescription information: (1) the prescriber's note as
      documented in the patient's chart; (2) the electronic prescription (e
      prescription) entered into the clinic's electronic prescribing software; (3) the
      medication that was ultimately dispensed by the pharmacy as indicated on the
      prescription label. The discrepancy rate was calculated by dividing the number of
      discrepancies identified by the number of prescriptions evaluated. RESULTS: A
      total of 602 prescriptions written by 33 prescribers were evaluated from the 3
      ambulatory care clinics. The discrepancy rate between the prescriber's note and
      the e-prescription was 1.7%, 0.6% and 3.9% for the three clinics. The discrepancy
      rate between the e-prescription (clinic) and the prescription label (pharmacy)
      was 4.2%, 0.9% and 1.5%. Differences between directions for administration was
      the most common type of discrepancy identified. CONCLUSIONS: Discrepancy rates
      between the prescriber's note and the e-prescription were similar to the
      discrepancy rates between the e-prescription and pharmacy label. To reduce
      outpatient medication errors, a better understanding is needed of the sources of
      discrepancies that occur within the prescriber's clinic, and those that occur
      between the clinic and pharmacy.

PMID- 24106313
TI  - Mobile phone health apps for diabetes management: current evidence and future
      developments.
AB  - Can an app help manage diabetes? We discuss how the advent of mobile health apps
      in connecting patients to providers is creating new opportunities for the
      management of diabetes. Although there are promising outcomes, there is still
      much to be learned about how such technology could be fully exploited. 

PMID- 24106312
TI  - Clinician approach to diagnosis of stress fractures including bisphosphonate
      associated fractures.
AB  - Stress fractures are repetitive strain injuries that occur in normal bones and in
      abnormal bones. Stress fractures share many features in common but differences
      depend on the status of the underlying bone. This review article for clinicians
      addresses aspects about stress fractures with particular respect to fatigue
      fractures, Looser zones of osteomalacia, atypical Looser zones, atypical femoral
      fractures associated with bisphosphonate therapy and stress fractures in Paget's
      disease of bone. 

PMID- 24106314
TI  - Acupuncture modulates the neuro-endocrine-immune network.
AB  - As a nonspecific physical stimulation, the effect of acupuncture on diseases is
      produced by motivating the inherent regulatory system in the body, having the
      characteristics of whole regulation, dual directional regulation, etc. Modern
      scientific researches show that body's inherent regulatory system is neuro
      endocrine-immune (NEI) network. Hence, we speculate that the regulatory effect of
      acupuncture may be produced through its regulation of NEI network. In this
      article, we reviewed the recent researches about acupuncture's effect on the NEI
      network, to find out the evidence of acupuncture adjusting NEI network and
      provide some evidences for revealing the mechanism of acupuncture. 

PMID- 24106315
TI  - The causes of hypopituitarism in the absence of abnormal pituitary imaging.
AB  - BACKGROUND: Hypopituitarism in the absence of a history of pituitary pathology or
      abnormal pituitary imaging is rare. AIM: To identify the cause of hypopituitarism
      in individuals in whom pituitary imaging was normal. DESIGN: Retrospective
      analysis of electronic patient record. METHOD: A review of the pituitary function
      in the 506 patients on the Morriston Hospital pituitary database revealed 230 had
      some degree of hypopituitarism and of these, 21 (9%) had normal pituitary
      imaging. RESULTS: Of this group, six patients had a past medical history of
      subarachnoid haemorrhage, head injury or meningitis, and mainly suffered from a
      deficiency of antidiuretic hormone. One patient had a stroke resulting in
      multiple anterior hormone deficiencies and six individuals had idiopathic cranial
      diabetes insipidus (DI). Subsequent investigations of the remaining eight
      patients with normal pituitary imaging revealed that two had neurosarcoidosis
      both of whom had panhypopituitarism. Four patients had haemochromatosis which
      resulted in gonadotropin deficiency in two, DI in one and panhypopituitarism in
      the other. There were two individuals with confirmed hypopituitarism and multiple
      hormone deficiencies in which no cause could be identified. CONCLUSION: These
      results show that hypopituitarism in the absence of pituitary pathology or an
      identifiable cause is rare. In patients with multiple anterior pituitary hormone
      deficiencies haemochromatosis and sarcoidosis should be considered.

PMID- 24106316
TI  - Thyroid papillary carcinoma in a 'hot' thyroid nodule.

PMID- 24106318
TI  - Evaluation of airway wall thickness via high-resolution computed tomography in
      mild intermittent asthma.
AB  - INTRODUCTION: This study aims to evaluate bronchial thickness via thorax high
      resolution computed tomography (HRCT) in subjects with mild intermittent asthma
      in comparison with healthy control subjects. METHODS: A total of 37 out-patients
      (mean +/- SD age = 36.7 years (9.7 years); 54.8% males) with mild intermittent
      asthma and 13 healthy control subjects (mean +/- SD age = 25.0 years (2.9 years);
      61.5% males) were included in this case control study. Data on demographics,
      pulmonary function test results, and segmental and subsegmental thorax HRCT
      results were recorded. The ratio of bronchial wall thickness to bronchial lumen
      diameter (T/D) and bronchial wall area percentage (WA%) were calculated for all
      cases. RESULTS: Subject and control groups were similar in terms of pulmonary
      function test results, and total and subsegmental T/D values. Mean +/- SD
      subsegmental WA% values at the level of inferior pulmonary vein (55.6% [16.8%]
      vs. 41.7% [7.4%], P = .047) and 2 cm above the diaphragm (49.8% [15.8%] vs. 38.6%
      [10.4%], P = .046) were significantly higher in subjects than control subjects.
      No significant correlation of overall and subsegmental T/D and WA% values to age
      in both groups, and to asthma duration in subjects. CONCLUSION: Our findings
      revealed an increase in bronchial wall thickness in peripheral airways in
      subjects with mild intermittent asthma regardless of the duration of asthma. This
      may indicate a need to also administer anti-inflammatory or bronchodilator
      therapy, which is effective in peripheral airways during the early period of the
      disease.

PMID- 24106317
TI  - Utilization of mechanical ventilation for asthma exacerbations: analysis of a
      national database.
AB  - BACKGROUND: The current frequency of noninvasive (NIV) and invasive mechanical
      ventilation use in asthma exacerbations (AEs) and the relationship to outcomes
      are unknown. METHODS: We used the Healthcare Cost and Utilization Project
      Nationwide Inpatient Sample to identify patients discharged with a principal
      diagnosis of AE. For each discharge, we determined whether NIV or invasive
      mechanical ventilation was initiated during the first 2 hospital days. Using
      multivariate logistic regression to adjust for potential confounders, we
      determined whether use of mechanical ventilation and in-hospital mortality
      changed between 2000 and 2008. RESULTS: The number of AEs increased by 15.8% from
      2000 to 2008. The proportion of admissions for which invasive mechanical
      ventilation was used during the first 2 days decreased from 1.4% in 2000 to 0.73%
      in 2008, whereas NIV use increased from 0.34% to 1.9%. The adjusted mortality
      from AEs requiring NIV or invasive mechanical ventilation was unchanged from 2000
      to 2008. The hospital stay was also unchanged. CONCLUSIONS: There was a
      substantial increase in the use of mechanical ventilation, accompanied by a shift
      from invasive mechanical ventilation to NIV. Although we could not determine the
      clinical reasons for this increase, hospital stay and mortality were unchanged. A
      randomized trial is needed to determine whether NIV can improve outcomes in AEs
      before widespread adoption makes it impossible to conduct such a trial.

PMID- 24106319
TI  - C-reactive protein, procalcitonin, clinical pulmonary infection score, and
      pneumonia severity scores in nursing home acquired pneumonia.
AB  - BACKGROUND: Patients with nursing home acquired pneumonia (NHAP) present a
      distinct group of lower respiratory track infections with different risk factors,
      clinical presentation, and mortality rates. OBJECTIVES: To evaluate the
      diagnostic value of clinical pulmonary infection score (CPIS), C-reactive
      protein, and procalcitonin and to compare the accuracy of pneumonia severity
      scores (confusion, urea nitrogen, breathing frequency, blood pressure, >= 65 y of
      age [CURB-65]; pneumonia severity index; NHAP index; systolic blood pressure,
      multilobar involvement, albumin, breathing frequency, tachycardia, confusion,
      oxygen, arterial pH [SMART-COP]; and systolic blood pressure, oxygen, age > 65 y,
      breathing frequency [SOAR]) in predicting in-patient mortality from NHAP.
      METHODS: Nursing home residents admitted to the hospital with acute respiratory
      illness were enrolled in the study. Subjects were classified as having NHAP
      (Group A) or other pulmonary disorders (Group B). Clinical, imaging, and
      laboratory data were assessed to compute CPIS and severity scores. C-reactive
      protein and procalcitonin were measured by immunonephelometry and immunoassay,
      respectively. RESULTS: Fifty-eight subjects were diagnosed with NHAP (Group A)
      and 29 with other pulmonary disorders (Group B). The mean C-reactive protein +/-
      SD was 16.38 +/- 8.6 mg/dL in Group A and 5.2 +/- 5.6 mg/dL in Group B (P <
      .001). The mean procalcitonin +/- SD was 1.52 +/- 2.75 ng/mL in Group A and 0.24
      +/- 0.21 ng/mL in Group B (P = .001). The mean CPIS +/- SD was 5.4 +/- 1.2 in
      Group A and 2.3 +/- 1.5 in Group B (P < .001). At a cutoff value of 0.475 ng/mL,
      procalcitonin had a sensitivity of 83% and a specificity of 72%. At a cutoff
      value of 8.05 mg/dL, C-reactive protein had a sensitivity of 81% and a
      specificity of 79%. Procalcitonin and C-reactive protein levels were
      significantly higher in Gram-positive NHAP. The in-patient mortality was 17.2% in
      Group A. Procalcitonin levels were 4.67 +/- 5.4 ng/mL in non-survivors and 0.86
      +/- 0.9 ng/mL in survivors (P < .001). The area under the curve for procalcitonin
      in predicting in-patient mortality was 0.84 (95% CI 0.70-0.98, P = .001). A
      procalcitonin level upon admission > 1.1 ng/mL was an independent predictor of in
      patient mortality. Of the pneumonia severity scores, CURB-65 showed greater
      accuracy in predicting in-patient mortality (area under the curve of 0.68, 95% CI
      0.53-0.84, P = .06). CONCLUSIONS: CPIS, procalcitonin, and C-reactive protein are
      reliable for the diagnosis of NHAP. Procalcitonin and CURB-65 are accurate in
      predicting in-patient mortality in NHAP.

PMID- 24106320
TI  - Improving aerosol drug delivery during invasive mechanical ventilation with
      redesigned components.
AB  - INTRODUCTION: Patients receiving invasive mechanical ventilation with an
      endotracheal tube (ETT) can often benefit from pharmaceutical aerosols; however,
      drug delivery through the ventilator circuit is known to be very inefficient. The
      objective of this study was to improve the delivery of aerosol through an
      invasive mechanical ventilation system by redesigning circuit components using a
      streamlining approach. METHODS: Redesigned components were the T-connector
      interface between the nebulizer and ventilator line and the Y-connector leading
      to the ETT. The streamlining approach seeks to minimize aerosol deposition and
      loss by eliminating sharp changes in flow direction and tubing diameter that lead
      to flow disruption. Both in vitro experiments and computational fluid dynamic
      (CFD) simulations were applied to analyze deposition and emitted dose of drug for
      multiple droplet size distributions, flows, and ETT sizes used in adults.
      RESULTS: The experimental results demonstrated that the streamlined components
      improved delivery through the circuit by factors ranging from 1.3 to 1.5 compared
      with a commercial system for adult ETT sizes of 8 and 9 mm. The overall delivery
      efficiency was based on the bimodal aspect of the aerosol distributions and could
      not be predicted by median diameter alone. CFD results indicated a 20-fold
      decrease in turbulence in the junction region for the streamlined Y resulting in
      a maximum 9-fold decrease in droplet deposition. The relative effectiveness of
      the streamlined designs was found to increase with increasing particle size and
      increasing flow, with a maximum improvement in emitted dose of 1.9-fold.
      CONCLUSIONS: Streamlined components can significantly improve the delivery of
      pharmaceutical aerosols during mechanical ventilation based on an analysis of
      multiple aerosol generation devices, ETT sizes, and flows.

PMID- 24106321
TI  - Pulmonary rehabilitation for mild COPD: a systematic review.
AB  - BACKGROUND: Pulmonary rehabilitation (PR) is effective in improving exercise
      capacity and health-related quality of life (HRQOL) in patients with moderate-to
      very-severe COPD. Quadriceps strength and HRQOL can be impaired in patients with
      mild COPD, therefore, patients at this grade may already benefit from PR.
      However, the impact of PR in patients with mild COPD remains unestablished. Thus,
      this systematic review assessed the impact of PR on exercise capacity, HRQOL,
      health-care resource use and lung function in patients with mild COPD. METHODS:
      The Web of Knowledge, EBSCO, MEDLINE, and SCOPUS databases were searched up to
      April 2013. Reviewers independently selected studies according to the eligibility
      criteria. RESULTS: Three studies with different designs (retrospective, one group
      pretest-posttest, and randomized controlled trial) were included. Out-patient PR
      programs were implemented in two studies, which included mainly aerobic,
      strength, and respiratory muscle training. The randomized controlled trial
      compared a PR home-based program, consisting of 6 months of walking and
      participating in ball games, with standard medical treatment. Significant
      improvements in exercise capacity (effect size [ES] 0.87-1.82) and HRQOL (ES 0.24
      0.86) were found when comparing pretest-posttest data and when comparing PR with
      standard medical treatment. In one study, a significant decrease in
      hospitalization days was found (ES 0.38). No significant effects were observed on
      the number of emergency department visits (ES 0.32), number of hospitalizations
      (ES 0.219), or lung function (ES 0.198). CONCLUSIONS: Most of the PR programs had
      significant positive effects on exercise capacity and HRQOL in patients with mild
      COPD; however, their effects on health-care resource use and lung function were
      inconclusive. This systematic review suggests that patients with mild COPD may
      benefit from PR; however, insufficient evidence is still available. Studies with
      robust designs and with longer follow-up times should be conducted.

PMID- 24106322
TI  - Detection of alpha-1 antitrypsin deficiency by respiratory therapists: experience
      with an educational program.
AB  - BACKGROUND: Alpha-1 antitrypsin deficiency is under-recognized. We hypothesized
      that respiratory therapists (RTs) could help improve the detection rate of
      individuals with alpha-1 antitrypsin deficiency. The American Association for
      Respiratory Care (AARC) and Alpha-1 Foundation recently collaborated to create an
      online alpha-1 antitrypsin deficiency training program for RTs. This study aimed
      to determine (1) the rate of RT enrollment in the training program, (2) the rates
      of detecting individuals with alpha-1 antitrypsin deficiency referred for testing
      by RTs who took the online course ("trained RTs"), and (3) the genotype
      distribution of referred individuals found to have alpha-1 antitrypsin
      deficiency. METHODS: Patients referred by trained RTs submitted blood samples for
      alpha-1 antitrypsin deficiency testing through the existing Alpha-1 Coded Testing
      (ACT) Study. The AARC sent the first 3 digits of trained RTs' zip codes to the
      study data center. Investigators there matched those zip codes with those of
      patients in the ACT Study who reported being referred to the study by an RT. The
      data center determined the number of these patients with alpha-1 antitrypsin
      deficiency and their genotypes. Investigators then aggregated the data and
      calculated the RT enrollment rate, the rate of detecting individuals with alpha-1
      antitrypsin deficiency, and the distribution of genotype results. RESULTS:
      Between July 1, 2012, and June 30, 2013, 378 RTs took the online program (mean
      21/mo), and 326 patients reported that they were referred for testing by an RT.
      Thirty-four percent (111/326) of these referrals were by trained RTs (6.2/mo).
      Sixty-two test blood kits were returned by these 111 referred patients and
      analyzed (4/mo). Two of these specimens (3.2%) were from patients identified as
      having severe alpha-1 antitrypsin deficiency (PI*ZZ) and one from a patient with
      PI*SZ (serum level 14 MUM). Twenty-four percent were from PI*MZ heterozygotes.
      CONCLUSIONS: A program to educate RTs about alpha-1 antitrypsin deficiency was
      associated with referral of patients for alpha-1 antitrypsin deficiency testing
      and high rates of detecting individuals with severe alpha-1 antitrypsin
      deficiency.

PMID- 24106323
TI  - Effect of oral hygiene and 0.12% chlorhexidine gluconate oral rinse in preventing
      ventilator-associated pneumonia after cardiovascular surgery.
AB  - BACKGROUND: Ventilator-associated pneumonia (VAP) is a nosocomial infection of
      multifactorial etiology and has a negative influence on cardiovascular surgery
      (CVS) outcomes. OBJECTIVES: Determine the effect of toothbrushing plus 0.12%
      chlorhexidine gluconate oral rinse in preventing VAP after CVS. METHODS: In a
      quasi-experimental study, patients undergoing heart surgery were enrolled in a
      protocol for controlling dental biofilm by proper oral hygiene (toothbrushing)
      and oral rinses with 0.12% chlorhexidine gluconate (Group 1), and they were
      compared with a historical control group (Group 2), which included patients who
      underwent cardiac surgery between 2009 and 2010 and who received regular oral
      hygiene care. Seventy-two hours before surgery, a dentist provided instruction
      and supervised oral hygiene with toothbrushing and chlorhexidine oral rinses to
      patients in Group 1. RESULTS: Each group comprised 150 patients. A lower
      incidence of VAP (2.7% [95% CI 0.7-7.8] vs 8.7% [95% CI 4.9-14.7], P = .04) and a
      shorter hospital stay (9 +/- 3 d [95% CI 8.5-9.5] vs 10 +/- 4 d [95% CI 9.4
      10.7], P = .01) were observed in Group 1. No significant differences in all-cause
      in-hospital death were observed between groups (5.3% vs 4.7%, P > .99). The risk
      for developing pneumonia after surgery was 3-fold higher in Group 2 (3.9, 95% CI
      1.1-14.2). CONCLUSIONS: Oral hygiene and mouth rinses with chlorhexidine under
      supervision of a dentist proved effective in reducing the incidence of VAP.

PMID- 24106324
TI  - Expiratory rib cage Compression in mechanically ventilated subjects: a randomized
      crossover trial [corrected].
AB  - BACKGROUND: Expiratory rib cage compression (ERCC) has been empirically used by
      physiotherapists with the rationale of improving expiratory flows and therefore
      the airway clearance in mechanically ventilated patients. This study evaluates
      the acute mechanical effects and sputum clearance of an ERCC protocol in
      ventilated patients with pulmonary infection. METHODS: In a randomized crossover
      study, sputum production and respiratory mechanics were evaluated in 20
      mechanically ventilated subjects submitted to 2 interventions. ERCC intervention
      consisted of a series of manual bilateral ERCCs, followed by a hyperinflation
      maneuver. Control intervention (CTRL) followed the same sequence, but instead of
      the compressive maneuver, the subjects were kept on normal ventilation. Static
      (Cst) and effective (C(eff)) compliance and total (R(tot)) and initial (R(init))
      resistance of the respiratory system were measured pre-ERCC (baseline), post-ERCC
      or CTRL (POST1), and post-hyperinflation (POST2). Peak expiratory flow (PEF) and
      the flow at 30% of the expiratory tidal volume (flow 30% VT) were measured during
      the maneuver. RESULTS: ERCC cleared 34.4% more secretions than CTRL (1 [0.5-1.95]
      vs 2 [1-3.25], P < .01). Respiratory mechanics showed no differences between
      control and experimental intervention in POST1 for Cst, Ceff, R(tot), and
      R(init). In POST2, ERCC promoted an increase in Cst (38.7 +/- 10.3 vs 42.2 +/- 12
      mL/cm H2O, P = .03) and in C(eff) (32.6 +/- 9.1 vs 34.8 +/- 9.4 mL/cm H2O, P =
      .04). During ERCC, PEF increased by 16.2 L/min (P < .001), and flow 30% VT
      increased by 25.3 L/min (P < .001) compared with CTRL. Six subjects (30%)
      presented expiratory flow limitation (EFL) during ERCC. The effect size was small
      for secretion volume (0.2), Cst (0.15), and C(eff) (0.12) and negligible for
      R(tot) (0.04) and R(init) (0.04). CONCLUSIONS: Although ERCC increases expiratory
      flow, it has no clinically relevant effects from improving the sputum production
      and respiratory mechanics in hypersecretive mechanically ventilated patients. The
      maneuver can cause EFL in some patients. (ClinicalTrials.gov registration
      NCT01525121).

PMID- 24106325
TI  - Influence of ambient temperature and minute ventilation on passive and active
      heat and moisture exchangers.
AB  - OBJECTIVE: During invasive mechanical ventilation, inspired gases must be
      humidified. We previously showed that high ambient temperature greatly impaired
      the hygrometric performance of heated wire-heated humidifiers. The aim of this
      bench and clinical study was to assess the humidification performance of passive
      and active heat and moisture exchangers (HMEs) and the impact of ambient
      temperature and ventilator settings. METHODS: We first tested on the bench a
      device with passive and active humidification properties (Humid-Heat, Teleflex),
      and 2 passive hydrophobic/hygroscopic HMEs (Hygrobac and Hygrobac S, Tyco
      Healthcare). The devices were tested at 3 different ambient temperatures (from 22
      to 30  degrees C), and at 2 minute ventilation settings (10 and 20 L/min).
      Inspired gas hygrometry was measured at the Y-piece with the psychrometric
      method. In addition to the bench study, we measured the hygrometry of inspired
      gases in 2 different clinical studies. In 15 mechanically ventilated patients, we
      evaluated Humid-Heat at different settings. Additionally, we evaluated Humid-Heat
      and compared it with Hygrobac in a crossover study in 10 patients. RESULTS: On
      the bench, with the Hygrobac and Hygrobac S the inspired absolute humidity was ~
      30 mg H2O/L, and with the Humid-Heat, slightly < 35 mg H2O/L. Ambient temperature
      and minute ventilation did not have a clinically important difference on the
      performance of the tested devices. During the clinical evaluation, Humid-Heat
      provided inspired humidity in a range from 28.5 to 42.0 mg H2O/L, depending on
      settings, and was only weakly influenced by the patient's body temperature.
      CONCLUSIONS: In this study both passive and active HMEs had stable humidification
      performance with negligible influence of ambient temperature and minute
      ventilation. This contrasts with previous findings with heated wire-heated
      humidifiers. Although there are no clear data demonstrating that higher
      humidification impacts outcomes, it is worth noting that humidity was
      significantly higher with the active HME.

PMID- 24106326
TI  - A randomized trial comparing the diagnostic yield of rigid and semirigid
      thoracoscopy in undiagnosed pleural effusions.
AB  - BACKGROUND: Thoracoscopic pleural biopsy increases the diagnostic yield of
      pleural effusions undiagnosed after thoracentesis and is superior to closed
      pleural biopsy. Medical thoracoscopy can be performed using the rigid
      thoracoscope or the semirigid thoracoscope (pleuroscope). In this randomized
      trial, we compare the efficacy and safety of the 2 thoracoscopes. METHODS:
      Subjects with undiagnosed exudative pleural effusions were randomly assigned to
      undergo pleural biopsy with either the rigid or the semirigid thoracoscope. The
      primary outcome was the diagnostic yield of the procedure, while the secondary
      outcomes were requirement of sedative/analgesic agents, scar size, biopsy sample
      size, and the operator's view of the procedure. RESULTS: Of the 145 screened
      subjects with exudative pleural effusions, 90 were randomized to undergo
      thoracoscopy with the 2 thoracoscopes (n = 45 each). The diagnostic yield of
      rigid thoracoscopy was superior to semirigid thoracoscopy (97.8% vs 73.3%, P =
      .002) on an intention-to-treat analysis but was similar (100% vs 94.3%, P = .18)
      in those with successful biopsy. The requirement of sedative/analgesic agents was
      higher in the rigid thoracoscopy arm. The scar size was slightly larger (mean +/-
      SD, 23.1 +/- 4 vs 18.7 +/- 3.2 mm, P = .0001), whereas the biopsy sample size was
      distinctly larger in the rigid arm (mean +/- SD, 13.9 +/- 4.4 vs 4.4 +/- 1.4 mm,
      P = .001). The operator-rated visual analog scale score for the ease of taking a
      biopsy sample was significantly higher with the rigid instrument (mean +/- SD,
      visual analog scale 86 +/- 12 vs 79 +/- 12 mm, P = .01), while the quality of
      image was superior in the semirigid arm (mean +/- SD, visual analog scale 88 +/-
      7 vs 92 +/- 5 mm, P = .002). The number of complications were similar in the 2
      groups. CONCLUSIONS: Rigid thoracoscopy was found to be superior to semirigid
      thoracoscopy overall, but the diagnostic yield was similar if pleural biopsy
      could be successfully performed. Due to the small sample size, a larger study is
      required to define the usefulness and choice between the 2 procedures.
      (ClinicalTrials.gov registration NCT01726556).

PMID- 24106327
TI  - Rrp47 functions in RNA surveillance and stable RNA processing when divorced from
      the exoribonuclease and exosome-binding domains of Rrp6.
AB  - The eukaryotic exosome exoribonuclease Rrp6 forms a complex with Rrp47 that
      functions in nuclear RNA quality control mechanisms, the degradation of cryptic
      unstable transcripts (CUTs), and in the 3' end maturation of stable RNAs. Stable
      expression of Rrp47 is dependent upon its interaction with the N-terminal domain
      of Rrp6 (Rrp6NT). To address the function of Rrp47 independently of Rrp6, we
      developed a DECOID (decreased expression of complexes by overexpression of
      interacting domains) strategy to resolve the Rrp6/Rrp47 complex in vivo and
      employed mpp6Delta and rex1Delta mutants that are synthetic lethal with loss-of
      function rrp47 mutants. Strikingly, Rrp47 was able to function in mpp6Delta and
      rex1Delta mutants when separated from the catalytic and exosome-binding domains
      of Rrp6, whereas a truncated Rrp47 protein lacking its C-terminal region caused a
      block in cell growth. Northern analyses of the conditional mutants revealed a
      specific block in the 3' maturation of box C/D snoRNAs in the rex1 rrp47 mutant
      and widespread inhibition of Rrp6-mediated RNA surveillance processes in the mpp6
      rrp47 mutant. In contrast, growth analyses and RNA northern blot hybridization
      analyses showed no effect on the rrp47Delta mutant upon overexpression of the
      Rrp6NT domain. These findings demonstrate that Rrp47 and Rrp6 have resolvable
      functions in Rrp6-mediated RNA surveillance and processing pathways. In addition,
      this study reveals a redundant requirement for Rrp6 or Rex1 in snoRNA maturation
      and demonstrates the effective use of the DECOID strategy for the resolution and
      functional analysis of protein complexes. 

PMID- 24106329
TI  - Activity size distribution of some natural radionuclides.
AB  - In this study, the results concerning the activity size distribution of the long
      lived ((210)Pb) radon decay product aerosols and the thoron decay product
      aerosols ((212)Pb) and ((7)Be) of the outdoor atmosphere are presented. Also, the
      mass size distribution of the aerosol particles is determined. The low-pressure
      Berner cascade impactor Model 20/0.015 was used as a sampling device. The
      activity size distribution of these radionuclides was determined by one log
      normal distribution (accumulation mode) whereas the mass size distribution was by
      two log-normal distributions (accumulation and coarse mode). The activity median
      aerodynamic diameter (AMAD) of (212)Pb was found to be 305 nm with a geometric
      standard deviation (sigmag) of 2.41. The specific air activity concentration of
      (212)Pb was found to be 0.14 +/- 0.012 Bq m(-3). An AMAD of (210)Pb of 610 nm
      with sigmag of 1.8 was determined, whereas that of 550 nm with sigmag of 1.97 was
      determined for (7)Be. The specific air activity concentration of (210)Pb and
      (7)Be was found to be 0.0016+/-2.5*10(-4) and 0.00348 +/- 4*10(-4) Bq m(-3),
      respectively. Using a dosimetric model, the total deposition fraction as well as
      the total equivalent dose has been evaluated considering the observed parameters
      of the activity size distribution of (212)Pb. At a total deposition fraction of
      ~21 %, the total equivalent dose was found to be 0.41 uSv. 

PMID- 24106328
TI  - Enhancement of hepatitis C viral RNA abundance by precursor miR-122 molecules.
AB  - The hepatitis C viral RNA genome forms a complex with liver-specific microRNA
      (miR-122) at the extreme 5' end of the viral RNA. This complex is essential to
      stabilize the viral RNA in infected cultured cells and in the liver of humans.
      The abundances of primary and precursor forms of miR-122, but not the abundance
      of mature miR-122, are regulated in a circadian rhythm in the liver of animals,
      suggesting a possible independent function of precursor molecules of miR-122 in
      regulating viral gene expression. Modified precursor molecules of miR-122 were
      synthesized that were refractory to cleavage by Dicer. These molecules were found
      to enhance the abundance of HCV RNA. Furthermore, they diminished the expression
      of mRNAs that contained binding sites for miR-122 in their 3' noncoding regions.
      By use of duplex and precursor miR-122 mimetic molecules that carried mutations
      in the passenger strand of miR-122, the effects on viral and reporter gene
      expression could be pinpointed to the action of precursor miR-122 molecules.
      Targeting the circadian expression of precursor miR-122 by specific compounds
      likely provides novel therapeutic strategies. 

PMID- 24106330
TI  - Indoor concentration of radon, thoron and their progeny around granite regions in
      the state of Karnataka, India.
AB  - An extensive studies on the indoor activity concentrations of thoron, radon and
      their progeny in the granite region in the state of Karnataka, India, has been
      carried out since, 2007 in the scope of a lung cancer epidemiological study using
      solid-state nuclear track detector-based double-chamber dosemeters (LR-115, type
      II plastic track detector). Seventy-four dwellings of different types were
      selected for the measurement. The dosemeters containing SSNTD detectors were
      fixed 2 m above the floor. After an exposure time of 3 months (90 d), films were
      etched to reveal tracks. From the track density, the concentrations of radon and
      thoron were evaluated. The value of the indoor concentration of thoron and radon
      in the study area varies from 16 to 170 Bq m(-3) and 18 to 300 Bq m(-3) with
      medians of 66 and 82.3 Bq m(-3), respectively, and that of their progeny varies
      from 1.8 to 24 mWL with a median of 3.6 mWL and 1.6 to 19.6 mWL, respectively.
      The concentrations of indoor thoron, radon and their progeny and their equivalent
      effective doses are discussed. 

PMID- 24106331
TI  - Measurement of the terrestrial and anthropogenic radionuclide concentrations in
      Bafra Kizilirmak delta (bird sanctuary) in Turkey.
AB  - In this study, the activity concentrations of terrestrial and anthropogenic
      radionuclides in the soil samples collected from Bafra Kizilirmak Delta were
      measured by using gamma spectrometry with an NaI(Tl) detector. The average values
      of activity concentrations of (238)U, (232)Th and (40)K were found to be 37.2+/
      2.8, 33.7+/-3.1 and 413.0+/-59.8 Bq kg(-1), respectively. (137)Cs was also
      measured in some samples. It has a mean value of 13.8+/-1.0 Bq kg(-1). From the
      activity concentrations, the absorbed gamma dose rates in outdoor and the
      corresponding annual effective dose rates and external hazard index (Hex) were
      estimated. 

PMID- 24106332
TI  - A radiometric and petrographic approach to risk assessment at Alte Madonie Mounts
      region (Sicily, Italy).
AB  - The main goal of this work was to assess the radiological hazard at Alte Madonie
      Mounts region (north-central Sicily, Italy) in response to rumours of an increase
      in the incidence of cancer in this area. A correlation between the natural
      radionuclide contents and the petrographic features of the soil and rock samples
      was also evaluated. A total of 41 samples of selected soils and rocks were
      collected, powdered, dried and sealed in 'Marinelli' beakers for 20 d prior to
      measurement to ensure that a radioactive equilibrium between (226)Ra and (214)Bi
      had been reached. A gamma-ray spectrometer was used to quantify the radioactivity
      concentrations. To determine (238)U and (232)Th activities, the 609.3-keV line
      from (214)Bi in secular equilibrium with (226)Ra and the 911-keV line from
      (228)Ac, with which (232)Th can be assumed to be in equilibrium, were used,
      respectively. The gamma transition of 1461 keV was used to determine (40)K
      activity. The average values of the concentrations of (214)Bi, (228)Ac and (40)K
      were 30, 17 and 227 Bq kg(-1), respectively, whereas the greatest values were
      134, 59 and 748 Bq kg(-1), respectively. A linear relationship was found between
      the activity values of (214)Bi, (228)Ac and (40)K. An exception was found for a
      group of samples in which the (214)Bi activities were much higher than expected.
      The chemical compositions and mineralogical features of the samples permitted the
      justification of these anomalies. The results of the primordial radionuclide
      contents are reassuring from a radiation protection point of view because the
      activities of the uranium and thorium series products and of the (40)K do not
      present a significant radiological hazard. 

PMID- 24106333
TI  - Individual differences in posterior cortical volume correlate with proneness to
      pride and gratitude.
AB  - Proneness to specific moral sentiments (e.g. pride, gratitude, guilt,
      indignation) has been linked with individual variations in functional MRI (fMRI)
      response within anterior brain regions whose lesion leads to inappropriate
      behaviour. However, the role of structural anatomical differences in rendering
      individuals prone to particular moral sentiments relative to others is unknown.
      Here, we investigated grey matter volumes (VBM8) and proneness to specific moral
      sentiments on a well-controlled experimental task in healthy individuals.
      Individuals with smaller cuneus, and precuneus volumes were more pride-prone,
      whereas those with larger right inferior temporal volumes experienced gratitude
      more readily. Although the primary analysis detected no associations with guilt-
      or indignation-proneness, subgenual cingulate fMRI responses to guilt were
      negatively correlated with grey matter volumes in the left superior temporal
      sulcus and anterior dorsolateral prefrontal cortices (right >left). This shows
      that individual variations in functional activations within critical areas for
      moral sentiments were not due to grey matter volume differences in the same
      areas. Grey matter volume differences between healthy individuals may
      nevertheless play an important role by affecting posterior cortical brain systems
      that are non-critical but supportive for the experience of specific moral
      sentiments. This may be of particular relevance when their experience depends on
      visuo-spatial elaboration. 

PMID- 24106334
TI  - Clonidine normalizes levels of P50 gating in patients with schizophrenia on
      stable medication.
AB  - BACKGROUND: Sensory gating deficits are among the core features of schizophrenia.
      Recently, we reported significantly increased sensorimotor gating following
      additional administration of single dosages of clonidine to the treatment of
      stably medicated patients with schizophrenia who, in spite of their medication,
      showed gating deficits. In the current study, we investigated whether this result
      is generalizable to filtering of sensory information as a whole, by examining
      clonidine's effect on P50 suppression in the same group of patients. METHODS: In
      a double-blind, placebo-controlled, randomized yet balanced cross-over design, 20
      male schizophrenia patients on stable medication were assessed in a
      psychophysiological test battery, including a sensory gating paradigm on 5
      occasions: once after oral administration of placebo and after single doses of
      25, 50, 75, and 150 ug of clonidine. Their results were compared with 20 age
      matched healthy male volunteers, who received no treatment. RESULTS: Patients
      showed significantly reduced levels of P50 suppression in the placebo session
      compared with controls. All dosages of clonidine significantly diminished these
      deficits to such levels that they no longer differed significantly from the
      healthy controls (except the highest dose). CONCLUSIONS: This is the first study
      to show that even a single low dose of clonidine administered to stably medicated
      patients with schizophrenia not only significantly increases their levels of P50
      suppression but also normalizes them. The results indicate that alpha2
      noradrenergic agonists are capable of normalizing levels of P50 gating, which has
      a potentially high clinical relevance for the medical treatment of schizophrenia.

PMID- 24106335
TI  - Efficacy of anti-inflammatory agents to improve symptoms in patients with
      schizophrenia: an update.
AB  - BACKGROUND: The inflammatory hypothesis of schizophrenia is not new, but recently
      it has regained interest because more data suggest a role of the immune system in
      the pathogenesis of schizophrenia. If increased inflammation of the brain
      contributes to the symptoms of schizophrenia, reduction of the inflammatory
      status could improve the clinical picture. Lately, several trials have been
      conducted investigating the potential of anti-inflammatory agents to improve
      symptoms of schizophrenia. This study provides an update regarding the efficacy
      of anti-inflammatory agents on schizophrenic symptoms in clinical studies
      performed so far. METHODS: An electronic search was performed using PubMed,
      Embase, the National Institutes of Health web site http://www.clinicaltrials.gov,
      Cochrane Schizophrenia Group entries in PsiTri, and the Cochrane Database of
      Systematic Reviews. Only randomized, double-blind, placebo-controlled studies
      that investigated clinical outcome were included. RESULTS: Our search yielded 26
      double-blind randomized controlled trials that provided information on the
      efficacy on symptom severity of the following components: aspirin, celecoxib,
      davunetide, fatty acids such as eicosapentaenoic acids and docosahexaenoic acids,
      estrogens, minocycline, and N-acetylcysteine (NAC). Of these components, aspirin
      (mean weighted effect size [ES]: 0.3, n = 270, 95% CI: 0.06-0.537, I(2) = 0),
      estrogens (ES: 0.51, n = 262, 95% CI: 0.043-0.972, I(2) = 69%), and NAC (ES:
      0.45, n = 140, 95% CI: 0.112-0.779) showed significant effects. Celecoxib,
      minocycline, davunetide, and fatty acids showed no significant effect.
      CONCLUSION: The results of aspirin addition to antipsychotic treatment seem
      promising, as does the addition of NAC and estrogens. These 3 agents are all very
      broadly active substances, and it has to be investigated if the beneficial
      effects on symptom severity are indeed mediated by their anti-inflammatory
      aspects.

PMID- 24106336
TI  - Prospective surface marker-based isolation and expansion of fetal endothelial
      colony-forming cells from human term placenta.
AB  - The term placenta is a highly vascularized tissue and is usually discarded upon
      birth. Our objective was to isolate clinically relevant quantities of fetal
      endothelial colony-forming cells (ECFCs) from human term placenta and to compare
      them to the well-established donor-matched umbilical cord blood (UCB)-derived
      ECFCs. A sorting strategy was devised to enrich for CD45-CD34+CD31Lo cells prior
      to primary plating to obtain pure placental ECFCs (PL-ECFCs) upon culture. UCB
      ECFCs were derived using a well-described assay. PL-ECFCs were fetal in origin
      and expressed the same cell surface markers as UCB-ECFCs. Most importantly, a
      single term placenta could yield as many ECFCs as 27 UCB donors. PL-ECFCs and UCB
      ECFCs had similar in vitro and in vivo vessel forming capacities and restored
      mouse hind limb ischemia in similar proportions. Gene expression profiles were
      only minimally divergent between PL-ECFCs and UCB-ECFCs, probably reflecting a
      vascular source versus a circulating source. Finally, PL-ECFCs and UCB-ECFCs
      displayed similar hierarchies between high and low proliferative colonies. We
      report a robust strategy to isolate ECFCs from human term placentas based on
      their cell surface expression. This yielded much larger quantities of ECFCs than
      UCB, but the cells were comparable in immunophenotype, gene expression, and in
      vivo functional ability. We conclude that PL-ECFCs have significant bio-banking
      and clinical translatability potential. 

PMID- 24106337
TI  - Adipose-derived cell construct stabilizes heart function and increases
      microvascular perfusion in an established infarct.
AB  - We have previously shown that myocardial infarction (MI) immediately treated with
      an epicardial construct containing stromal vascular fraction (SVF) from adipose
      tissue preserved microvascular function and left ventricle contractile
      mechanisms. In order to evaluate a more clinically relevant condition, we
      investigated the cardiac recovery potential of an SVF construct implanted onto an
      established infarct. SVF cells were isolated from rat adipose tissue, plated on
      Vicryl, and cultured for 14 days. Fischer-344 rats were separated into MI groups:
      (a) 6-week MI (MI), (b) 6-week MI treated with an SVF construct at 2 weeks (MI
      SVF), (c) 6-week MI with Vicryl construct at 2 weeks (MI Vicryl), and (d) MI 2wk
      (time point of intervention). Emax, an indicator of systolic performance and
      contractile function, was lower in the MI and MI Vicryl versus MI SVF. Positron
      emission tomography imaging ((18)F-fluorodeoxyglucose) revealed a decreased
      percentage of relative infarct volume in the MI SVF versus MI and MI Vicryl.
      Total vessel count and percentage of perfusion assessed via immunohistochemistry
      were both increased in the infarct region of MI SVF versus MI and MI Vicryl.
      Overall cardiac function, percentage of relative infarct, and percentage of
      perfusion were similar between MI SVF and MI 2wk; however, total vessel count
      increased after SVF treatment. These data suggest that SVF treatment of an
      established infarct stabilizes the heart at the time point of intervention by
      preventing a worsening of cardiac performance and infarcted volume, and is
      associated with increased microvessel perfusion in the area of established
      infarct. 

PMID- 24106338
TI  - Evaluation of the anatomical site distribution of chlamydia and gonorrhoea in men
      who have sex with men and in high-risk women by routine testing: cross-sectional
      study revealing missed opportunities for treatment strategies.
AB  - OBJECTIVES: Current strategies for controlling non-urogenital chlamydia and
      gonorrhoea are not uniform. It is assumed that present anorectal/oropharyngeal
      infections are coincidentally treated with urogenital infections. However, it is
      not clear whether this control strategy is effective. To inform current debate,
      we evaluated the anatomical site distribution of chlamydia and gonorrhoea by
      routine testing in men who have sex with men (hereafter men) and in high-risk
      women (prostitutes and swingers, hereafter women). METHODS: Between January 2010
      and November 2012, all men (n=2436) and women (n=1321) attending our sexually
      transmitted infection clinic were routinely tested for anorectal, oropharyngeal
      and urogenital Chlamydia trachomatis and Neisseria gonorrhoeae. Data were
      collected on demographics and sexual behaviour. RESULTS: Overall chlamydia
      positivity was 10.4% (254/2436) in men and 7.0% (92/1321) in women, for
      gonorrhoea this was 6.3% (154/2436) and 3.1% (41/1321), respectively. Isolated
      non-urogenital infections amounted to 76% of all infections in men and for up to
      59% of all infections in women. For combined urogenital and anorectal infections,
      this amounted to 14% for men and up to 54% for women. CONCLUSIONS: Testing only
      for non-urogenital infections is insufficient, as it overlooks many infections.
      The use of coincidental treatment is therefore a suboptimal control strategy in
      high-risk groups for halting complications and transmission. There is an urgent
      need to optimise the testing guidelines for chlamydia and gonorrhoea at different
      anatomical sites.

PMID- 24106339
TI  - Current and future treatment options for gonorrhoea.
AB  - The delivery of effective antimicrobial therapy is essential for public health
      control of gonorrhoea, in the absence of a suitable vaccine. The antimicrobial
      agent chosen should have high efficacy and quality, lack toxicity and give >95%
      success when given empirically. Guidelines, which are informed by surveillance
      data, are used to aid clinicians in their choice of appropriate agent.
      Historically, gonorrhoea treatment has been delivered as a single, directly
      observed dose but this has resulted in failure of successive antimicrobial agents
      which have been replaced by a new antimicrobial to which resistance has been rare
      or non-existing. Following the drift towards decreased susceptibility and
      treatment failure to the extended spectrum cephalosporins, and the lack of 'new'
      alternative antimicrobials, the threat of difficult to treat or untreatable
      gonorrhoea has emerged. The challenge of maintaining gonorrhoea as a treatable
      infection has resulted in national, regional and global response or action plans.
      This review discusses different approaches to the future treatment of gonorrhoea
      including; use of ceftriaxone, the injectable cephalosporin at increased dosage;
      dual antimicrobial therapy; use of drugs developed for other infections and use
      of older agents, directed by rapid point of care tests, to susceptible
      infections. Finally, it is considered whether the time is right to readdress the
      possibility of developing an effective gonococcal vaccine, given the major
      advances in our understanding of natural infection, molecular pathogenesis and
      the revolution in molecular biology techniques. 

PMID- 24106340
TI  - Suboptimal adherence to doxycycline and treatment outcomes among men with non
      gonococcal urethritis: a prospective cohort study.
AB  - OBJECTIVE: Doxycycline, one of two recommended therapies for non-gonococcal
      urethritis (NGU), consists of a 7-day course of therapy (100 mg BID). Since
      suboptimal adherence may contribute to poor treatment outcomes, we examined the
      association between self-reported imperfect adherence to doxycycline and clinical
      and microbiologic failure among men with NGU. METHODS: Men aged >=16 years with
      NGU attending a Seattle, WA, sexually transmitted diseases clinic were enrolled
      in a double-blind, parallel-group superiority trial from January 2007 to July
      2011. Men were randomised to active doxycycline/placebo azithromycin or placebo
      doxycycline/active azithromycin. Imperfect adherence was defined as missing >=1
      dose in 7 days. Urine was tested for Chlamydia trachomatis (CT), Mycoplasma
      genitalium (MG), and Ureaplasma urealyticum-biovar 2 (UU-2) using nucleic acid
      amplification tests. Clinical failure (symptoms and >=5 PMNs/HPF or discharge)
      and microbiologic failure (positive tests for CT, MG, and/or UU-2) were
      determined after 3 weeks. RESULTS: 184 men with NGU were randomised to active
      doxycycline and provided data on adherence. Baseline prevalence of CT, MG and UU
      2 was 26%, 13% and 27%, respectively. 28% of men reported imperfect adherence,
      and this was associated with microbiologic failure among men with CT (aRR=9.33;
      95% CI 1.00 to 89.2) and UU-2 (aRR=3.08; 95% CI 1.31 to 7.26) but not MG.
      Imperfect adherence was not significantly associated with clinical failure
      overall or for any specific pathogens, but it was more common among imperfectly
      adherent men with CT (aRR=2.63; 0.93-7.41, p=0.07). CONCLUSIONS: Adherence may be
      important for microbiologic cure of select pathogens. Factors other than
      adherence should be considered for CT-negative men with persistent NGU.

PMID- 24106341
TI  - Lipid-induced toxicity stimulates hepatocytes to release angiogenic
      microparticles that require Vanin-1 for uptake by endothelial cells.
AB  - Angiogenesis is a key pathological feature of experimental and human
      steatohepatitis, a common chronic liver disease that is associated with obesity.
      We demonstrated that hepatocytes generated a type of membrane-bound vesicle,
      microparticles, in response to conditions that mimicked the lipid accumulation
      that occurs in the liver in some forms of steatohepatitis and that these
      microparticles promoted angiogenesis. When applied to an endothelial cell line,
      medium conditioned by murine hepatocytes or a human hepatocyte cell line exposed
      to saturated free fatty acids induced migration and tube formation, two processes
      required for angiogenesis. Medium from hepatocytes in which caspase 3 was
      inhibited or medium in which the microparticles were removed by
      ultracentrifugation lacked proangiogenic activity. Isolated hepatocyte-derived
      microparticles induced migration and tube formation of an endothelial cell line
      in vitro and angiogenesis in mice, processes that depended on internalization of
      microparticles. Microparticle internalization required the interaction of the
      ectoenzyme Vanin-1 (VNN1), an abundant surface protein on the microparticles,
      with lipid raft domains of endothelial cells. Large quantities of hepatocyte
      derived microparticles were detected in the blood of mice with diet-induced
      steatohepatitis, and microparticle quantity correlated with disease severity.
      Genetic ablation of caspase 3 or RNA interference directed against VNN1 protected
      mice from steatohepatitis-induced pathological angiogenesis in the liver and
      resulted in a loss of the proangiogenic effects of microparticles. Our data
      identify hepatocyte-derived microparticles as critical signals that contribute to
      angiogenesis and liver damage in steatohepatitis and suggest a therapeutic target
      for this condition. 

PMID- 24106342
TI  - Heteromeric MT1/MT2 melatonin receptors modulate photoreceptor function.
AB  - The formation of G protein (heterotrimeric guanine nucleotide-binding protein)
      coupled receptor (GPCR) heteromers enables signaling diversification and holds
      great promise for improved drug selectivity. Most studies of these
      oligomerization events have been conducted in heterologous expression systems,
      and in vivo validation is lacking in most cases, thus questioning the
      physiological significance of GPCR heteromerization. The melatonin receptors MT1
      and MT2 exist as homomers and heteromers when expressed in cultured cells. We
      showed that melatonin MT1/MT2 heteromers mediated the effect of melatonin on the
      light sensitivity of rod photoreceptors in mice. This effect of melatonin
      involved activation of the heteromer-specific phospholipase C and protein kinase
      C (PLC/PKC) pathway and was abolished in MT1(-/-) or MT2(-/-) mice, as well as in
      mice overexpressing a nonfunctional MT2 mutant that interfered with the formation
      of functional MT1/MT2 heteromers in photoreceptor cells. Not only does this study
      establish an essential role of melatonin receptor heteromers in retinal function,
      it also provides in vivo support for the physiological importance of GPCR
      heteromerization. Thus, the MT1/MT2 heteromer complex may provide a specific
      pharmacological target to improve photoreceptor function. 

PMID- 24106343
TI  - Hippo gains weight: added insights and complexity to pathway control.
AB  - The Hippo pathway is a kinase cascade, formed by Hippo, Salvador, Warts, and
      Mats, that regulates the subcellular distribution and transcriptional activity of
      Yorkie. Yorkie is a transcriptional coactivator that promotes the expression of
      genes that inhibit apoptosis and drive cell proliferation. We review recent
      studies indicating that activity of the Hippo pathway is controlled by cell-cell
      junctions, cell adhesion molecules, scaffolding proteins, and cytoskeletal
      proteins, as well as by regulators of apical-basal polarity and extracellular
      tension. 

PMID- 24106344
TI  - Altered profile of chemokines in fibromyalgia patients.
AB  - BACKGROUND: Fibromyalgia (FM) is a syndrome characterized by widespread chronic
      pain. Its aetiology is still poorly understood, and there are no haematochemical
      or instrumental tests on which to base a diagnosis. Recent studies suggest that
      its pathogenesis may involve cytokines, in particular, chemokines - cytokines
      that regulate cell traffic under both physiological and pathological conditions.
      The aim of this study was to determine possible differences in the profile of
      systemic concentrations of chemokines between FM patients and healthy women (HW;
      controls). METHODS: The study participants were women diagnosed with FM (n = 17)
      and a control group of HW (n = 10). Serum concentrations of thymus and activation
      regulated chemokine (TARC)/(CCL17), monokine induced by gamma-interferon
      (MIG)/(CXCL9), macrophage-derived chemokine (MDC)/(CCL22), interferon-inducible T
      cell alpha chemoattractant (I-TAC)/(CXCL11), eotaxin (CCL11), pulmonary and
      activation-regulated chemokine (PARC)/(CCL18) and hemofiltrate CC-chemokine-4
      (HCC-4)/(CCL16) were determined by enzyme-linked immunosorbent assay and compared
      between the FM and HW groups. RESULTS: FM patients had elevated serum levels of
      the following inflammatory chemokines: TARC (P < 0.001), MIG (P < 0.001), MDC (P
      < 0.01), I-TAC (P < 0.01) and eotaxin (P < 0.05). No differences were found in
      the circulating concentrations of PARC and HCC-4 (homoeostatic chemokines).
      CONCLUSIONS: Since FM patients present higher serum concentrations of
      inflammatory chemokines than HW, the evaluation of these biomarkers could help in
      the diagnosis of this syndrome.

PMID- 24106347
TI  - Minimizing medication errors: Moving attention from individual to system.

PMID- 24106348
TI  - Anesthesiology research and practice in developing nations: Economic and evidence
      based patient-centered approach.

PMID- 24106349
TI  - Surgeons and anesthesiologists: Need to communicate?

PMID- 24106350
TI  - Role of colloids in traumatic brain injury: Use or not to be used?
AB  - Trauma is a leading cause of death worldwide and traumatic brain injury is one of
      the commonest injuries associated with it. The need for urgent resuscitation is
      warranted for prevention of secondary insult to brain. However, the choice of
      fluid in such cases is still a matter of conflict. The literature does not
      provide enough data pertaining to role of colloids in head injury patients. In
      this article, we have tried to explore the present role of colloid resuscitation
      in patient with head injury. 

PMID- 24106351
TI  - Neuraxial opioid-induced pruritus: An update.
AB  - Pruritus is a troublesome side-effect of neuraxial (epidural and intrathecal)
      opioids. Sometimes it may be more unpleasant than pain itself. The prevention and
      treatment still remains a challenge. A variety of medications with different
      mechanisms of action have been used for the prevention and treatment of opioid
      induced pruritus, with mixed results. The aim of this article is to review the
      current body of literature and summarize the current understanding of the
      mechanisms and the pharmacological therapies available to manage opioid-induced
      pruritus. The literature source of this review was obtained via PubMed, Medline
      and Cochrane Database of Systematic Reviews until 2012. The search results were
      limited to the randomized controlled trials, systemic reviews and non-systemic
      reviews. 

PMID- 24106352
TI  - Assessment of cervical spine movement during laryngoscopy with Macintosh and
      Truview laryngoscopes.
AB  - BACKGROUND: Truview laryngoscope provides an indirect view of the glottis and
      will cause less cervical spine movement since a ventral lifting force will not be
      required to visualize the glottis compared to Macintosh laryngoscope. MATERIALS
      AND METHODS: A randomized crossover study to assess the degree of movement of
      cervical spine during endotracheal intubation with Truview laryngoscope was
      conducted in 25 adult ASA-I patients. After a standard anesthetic technique
      laryngoscopy was performed twice in each patient using in turn both the Macintosh
      and Truview laryngoscopes. A baseline radiograph with the head and neck in a
      neutral position was followed by a second radiograph taken during each
      laryngoscopy. An experienced radiologist analyzed and measured the cervical
      movement. RESULTS: Significant cervical spine movement occurred at all segments
      when compared to the baseline with both the Macintosh and Truview laryngoscopes
      (P < 0.001). However, the movement was significantly less with Truview compared
      to the Macintosh laryngoscope at C0-C1 (21%; P = 0.005) and C1-C2 levels (32%; P
      = 0.009). The atlantooccipital distance (AOD) traversed while using Truview
      laryngoscope was significantly less than with Macintosh blade (26%; P = 0.001).
      Truview blade produced a better laryngoscopic view (P = 0.005) than Macintosh
      blade, but had a longer time to laryngoscopy (P = 0.04). CONCLUSION: Truview
      laryngoscope produced a better laryngoscopic view of glottis as compared with
      Macintosh laryngoscopy. It also produced significantly less cervical spine
      movement at C0-C1 and C1-C2 levels than with Macintosh laryngoscope in patients
      without cervical spine injury and without manual in-line stabilization (MILS).
      Further studies are warranted with Truview laryngoscope using MILS.

PMID- 24106353
TI  - Comparison of Mallampati test with lower jaw protrusion maneuver in predicting
      difficult laryngoscopy and intubation.
AB  - BACKGROUND: Failure to maintain a patent airway is one of the commonest causes of
      anesthesia-related morbidity and mortality. Many protocols, algorithms, and
      different combinations of tested methods for airway assessment have been
      developed to predict difficult laryngoscopy and intubation. The reported
      incidence of a difficult intubation varies from 1.5% to 13%. The objective of
      this study was to compare Mallampati test (MT) with lower jaw protrusion (LJP)
      maneuver in predicting difficult laryngoscopy and intubation. MATERIALS AND
      METHODS: Seven hundred and sixty patients were included in the study. All the
      patients underwent MT and LJP maneuver for their airway assessment. After a
      standardized technique of induction of anesthesia, primary anesthetist performed
      laryngoscopy and graded it according to the grades described by Cormack and
      Lehane. Sensitivity, specificity, accuracy, and positive predictive value (PPV)
      and negative predictive value (NPV) were calculated for both these tests with 95%
      confidence interval (CI) using conventional laryngoscopy as gold standard. Area
      under curve was also calculated for both, MT and LJP maneuver. A P < 0.05 was
      taken as significant. RESULTS: LJP maneuver had higher sensitivity (95.9% vs.
      27.1%), NPV (98.7% vs. 82.0%), and accuracy (90.1% vs. 80.3%) when compared to MT
      in predicting difficult laryngoscopy and intubation. Both tests, however, had
      similar specificity and PPV. There was marked difference in the positive and
      negative likelihood ratio between LJP and MT. Similarly, the area under the curve
      favored LJP maneuver over MT. CONCLUSION: The results of this study show that LJP
      maneuver is a better test to predict difficult laryngoscopy and tracheal
      intubation. We recommend the addition of this maneuver to the routine
      preoperative evaluation of airway.

PMID- 24106354
TI  - The effect of dexmedetomidine continuous infusion as an adjuvant to general
      anesthesia on sevoflurane requirements: A study based on entropy analysis.
AB  - BACKGROUND: Dexmedetomidine, a alpha2 agonist as an adjuvant in general
      anesthesia, has anesthetic and analgesic-sparing property. AIMS: To evaluate the
      effect of continuous infusion of dexmedetomidine alone, without use of opioids,
      on requirement of sevoflurane during general anesthesia with continuous
      monitoring of depth of anesthesia by entropy analysis. MATERIALS AND METHODS:
      Sixty patients were randomly divided into 2 groups of 30 each. In group A,
      fentanyl 2 mcg/kg was given while in group B, dexmedetomidine was given
      intravenously as loading dose of 1 mcg/kg over 10 min prior to induction. After
      induction with thiopentone in group B, dexmedetomidine was given as infusion at a
      dose of 0.2-0.8 mcg/kg. Sevoflurane was used as inhalation agent in both groups.
      Hemodynamic variables, sevoflurane inspired fraction (FIsevo), sevoflurane
      expired fraction (ETsevo), and entropy (Response entropy and state entropy) were
      continuously recorded. Statistical analysis was done by unpaired student's t-test
      and Chi-square test for continuous and categorical variables, respectively. A P
      value < 0.05 was considered significant. RESULTS: The use of dexmedetomidine with
      sevoflurane was associated with a statistical significant decrease in ETsevo at 5
      minutes post-intubation (1.49 +/- 0.11) and 60 minutes post-intubation (1.11 +/
      0.28) as compared to the group A [1.73 +/-0.30 (5 minutes); 1.68 +/-0.50 (60
      minutes)]. There was an average 21.5% decrease in ETsevo in group B as compared
      to group A. CONCLUSIONS: Dexmedetomidine, as an adjuvant in general anesthesia,
      decreases requirement of sevoflurane for maintaining adequate depth of
      anesthesia.

PMID- 24106355
TI  - Perioperative concerns in pediatric patients u10/1/2013ndergoing different types
      of scoliosis correction surgery: A retrospective observational study.
AB  - BACKGROUND: Advances in scoliosis surgery have now made it possible for younger
      patients to be taken up for scoliosis correction. OBJECTIVES: To ascertain the
      patient profile, perioperative complications and need for intensive care
      management in children undergoing posterior fusion and instrumentation (PF),
      anterior release (AR), and growth rod (GR) insertion surgery. PATIENTS AND
      METHODS: After taking parental consent, data were collected retrospectively for
      33 patients who underwent 37 procedures (four patients had both anterior and
      posterior procedures) on 2 days of the week mainly from August 2008 to February
      2010 at a tertiary care institution. RESULTS: Children undergoing GR surgery were
      younger (8.1 +/- 2.1 years) than patients undergoing AR (12.9 +/- 1.7 years) or
      posterior fusion (14.2 +/- 2.2 years). AR children had a significantly higher
      Cobb's angle and more rigid curves. (P = 0.057) Associated congenital
      abnormalities especially neurological were commoner in the GR children. Surgical
      duration and blood loss was significantly more for PF (2207.5 +/- 1224.13 ml)
      than GR (456 +/- 337.5 ml), or AR (642.85 +/- 304.72 ml), (P = 0.0002). PF
      patients needed Intensive care unit (ICU) care mainly due to the blood loss and
      prolonged surgery (35%). AR performed via thoracotomy was associated with the
      need for mechanical ventilation in 28.6%. The GR patients had major
      intraoperative hemodynamic events and 20% needed ICU care. CONCLUSIONS: Post
      operative ventilation may be required in 20-35% patients undergoing procedures
      for scoliosis correction. Despite GR insertion involving lesser blood loss;
      younger age, congenital abnormalities, positioning, and surgical manipulation
      resulted in life threatening events in these patients.

PMID- 24106356
TI  - Pharmaco-economics: Minute-based cost of sevoflurane in pediatric short
      procedures and its relation to demographic variables.
AB  - BACKGROUND: Inhalation agents account for significant cost of short daycare
      procedures. The estimation of this cost to pre-calculate expected expenditure is
      not available in literature. As for intravenous agents, their relations to weight
      and other demographic parameters are also not well established. The present study
      aims to evaluate the above concern. MATERIALS AND METHODS: A total of 100
      pediatric (ASA I, II) patients scheduled for ophthalmological examination under
      anesthesia (EUA) were included in the study. Following premedication, anesthesia
      in all children was induced using incremental concentrations of sevoflurane at a
      flow of 6 l with 1:1 oxygen:nitrous oxide ratio. Upon induction, the flows were
      reduced to 2 l, keeping sevoflurane at 1 to 2 minimum alveolar concentration
      (MAC). Using Dion's equation, the costs for induction and maintenance with
      sevoflurane were calculated for each patient. RESULTS: The cost per minute of
      sevoflurane was found to be Rs. 13.23. Unlike intravenous agents, no significant
      correlation was found to exist between sevoflurane consumption with age or
      weight. The sevoflurane consumption was also not influenced by the gender. The
      total cost of EUA correlated most strongly with duration of maintenance phase,
      followed by induction duration.

PMID- 24106357
TI  - Composite auditory evoked potentials index is not a good indicator of depth of
      anesthesia in propofol-fentanyl anesthesia: Randomized comparative study.
AB  - BACKGROUND: The composite auditory evoked potentials index (cAAI) was considered
      a measure of overall balance between noxious stimulation, analgesia, and
      hypnosis; while bispectral index (BIS) shows only hypnosis, and auditory evoked
      potentials index (AAI) shows response to stimuli. The present study compared the
      performance of cAAI, BIS, and AAI in propofol-fentanyl anesthesia. MATERIALS AND
      METHODS: Forty-five patients for abdominal surgery aged 30-65 years with ASA
      physical status I or II were randomly divided into three groups by an envelope
      method. Anesthesia was induced with midazolam, propofol, and fentanyl alongwith
      an epidural block. When hemodynamics were stable during surgery, propofol
      infusion rate was fixed at 4 mg/kg/h for 10 min, then increased to 6 mg/kg/h and
      kept it for 10 min. AAI (AEP version 1.4), cAAI (AEP version 1.6), or BIS (A
      2000) was monitored in each 15 patients, and the performance of three indices was
      compared. RESULTS: All three indices decreased significantly before intubation.
      Only the AAI increased significantly by intubation. During anesthesia except for
      at propofol 6 mg/kg/h, the cAAI was significantly higher than the AAI. Only the
      AAI was significantly lower at propofol 6 mg/kg/h than at 4 mg/kg/h. The cAAI had
      the largest and AAI had the smallest inter-individual variations. The cAAI was
      higher than the manufacturer's recommended range of general anesthesia.
      CONCLUSION: In propofol-fentanyl anesthesia, AAI might be better to discriminate
      anesthetic depth than cAAI and BIS.

PMID- 24106358
TI  - Effect of gender on pain perception and analgesic consumption in laparoscopic
      cholecystectomy: An observational study.
AB  - BACKGROUND: Evidence regarding gender affecting the response to pain and its
      treatment is inconsistent in literature. The objective of this prospective,
      observational study was to determine the effect of gender on pain perception and
      postoperative analgesic consumption in patients undergoing laparoscopic
      cholecystectomy. MATERIALS AND METHODS: We recruited 60 male and 60 female
      patients undergoing elective laparoscopic cholecystectomy. Patients were observed
      for additional intraoperative and postoperative analgesia. Numerical rating scale
      was documented at 10 min interval for 1 h in post-anesthesia recovery room and at
      4, 8, and 12 h postoperatively. Boluses of tramadol given as rescue analgesia
      were also noted. There were no dropouts. RESULTS: The mean pain scores were
      significantly higher in female patients at 20 and 30 min following surgery. Mean
      dose of tramadol consumption was significantly higher in female patients for the
      first postoperative hour (P = 0.002), but not in the later period. CONCLUSION:
      Female patients exhibited greater intensity of pain and required higher doses of
      analgesics compared to males in in the immediate postoperative period in order to
      achieve a similar degree of analgesia.

PMID- 24106359
TI  - Intravenous dexmedetomidine versus clonidine for prolongation of bupivacaine
      spinal anesthesia and analgesia: A randomized double-blind study.
AB  - BACKGROUND: Alpha2-adrenergic agonists have synergistic action with local
      anesthetics and may prolong the duration of sensory, motor blockade and
      postoperative analgesia obtained with spinal anesthesia. AIM: The objectives of
      this study are to compare and evaluate the efficacy of intravenous
      dexmedetomidine premedication with clonidine and placebo on spinal blockade
      duration, postoperative analgesia and sedation in patients undergoing surgery
      under bupivacaine intrathecal block. MATERIALS AND METHODS: In this prospective,
      randomized, double-blind placebo-controlled study, 75 patients of the American
      Society of Anesthesiologists status I or II, scheduled for orthopedic lower limb
      surgery under spinal anesthesia, were randomly allocated into three groups of 25
      each. Group DE received dexmedetomidine 0.5 MUgkg(-1), group CL received
      clonidine 1.0 MUgkg(-1) and placebo group PL received 10 ml of normal saline
      intravenously before subarachnoid anesthesia with 15 mg of 0.5% hyperbaric
      bupivacaine. Onset time and regression times of sensory and motor blockade, the
      maximum upper level of sensory blockade were recorded. Duration of postoperative
      analgesia and sedation scores along with side effects were also recorded. Data
      was analyzed using analysis of variance or Chi-square test, and the value of P <
      0.05 was considered statistically significant. RESULTS: The sensory block level
      was higher with dexmedetomidine (T4 +/- 1) than clonidine (T6 +/- 1) or placebo
      (T6 +/- 2). Dexmedetomidine also increased the time (243.35 +/- 56.82 min) to
      first postoperative analgesic request compared with clonidine (190.93 +/- 42.38
      min, P < 0.0001) and placebo (140.75 +/- 28.52 min, P < 0.0001). The maximum
      Ramsay sedation score was greater in the dexmedetomidine group than other two
      groups (P < 0.0001). CONCLUSION: Premedication with intravenous dexmedetomidine
      is better than intravenous clonidine to provide intraoperative sedation and
      postoperative analgesia during bupivacaine spinal anesthesia.

PMID- 24106361
TI  - Evaluation of analgesic effect of local administration of morphine after iliac
      crest bone graft harvesting: A double blind study.
AB  - BACKGROUND AND OBJECTIVE: Pain is a complex process influenced by both
      physiological and psychological factors. In spite of an armamentarium of
      analgesic drugs and techniques available to combat post-operative pain,
      appropriate selection, and effective management for relief of post-operative pain
      still poses unique challenges. The discovery of peripheral opioid receptors has
      led to growing interest in the use of locally applied opioids (intra-articular,
      intra-pleural, intra-peritoneal, and perineural) for managing acute pain. As bone
      graft harvesting is associated with significant post-operative pain and there is
      a paucity of literature on the use of peripheral opioids at the iliac crest bone
      harvesting site, the present study was planned to evaluate the analgesic efficacy
      of local administration of morphine after iliac crest bone graft harvesting.
      MATERIALS AND METHODS: A total of 60 patients, 20-50 years of age scheduled to
      undergo elective surgery for delayed and non-union fracture both bone leg with
      bone grafting under general anaesthesia (GA) were randomly assigned to one of the
      four groups of 15 patients each: group 1: 2.5 ml normal saline (NS) +2.5 ml NS
      infiltrated into the harvest site at 2 sites + 1 ml NS intramuscularly (i/m);
      Group 2: 2.5 ml NS + 2.5 ml NS infiltrated into the harvest site at 2 sites + 5
      mg morphine in 1 ml i/m.; Group 3: 2.5 mg (2.5 ml) morphine + 2.5 mg (2.5 ml)
      morphine infiltrated into the harvest site at 2 sites + 1 ml NS i/m; Group 4: 0.5
      mg naloxone (2.5 ml) +5 mg (2.5 ml) morphine infiltrated into the harvest site at
      2 sites + 1 ml NS i/m. Pain from the bone graft site and operative site was
      assessed for 24 h post-operatively. RESULTS: The patients who had received
      morphine infiltration (Group 3) had significantly less pain scores at the graft
      site at 4, 6, and 10 post-operative hours. They also had significantly less
      morphine consumption and overall better pain relief as compared to the other
      groups. CONCLUSIONS: Morphine administered peripherally provided better analgesia
      as compared to that given systemically and this effect was noticeable after 4 h
      post-operatively.

PMID- 24106360
TI  - Colloid cohydration and variable rate phenylephrine infusion effectively prevents
      postspinal hypotension in elective Cesarean deliveries.
AB  - BACKGROUND: Prevention of post-spinal hypotension in obstetric patients can be
      accomplished using intravenous fluid expansion and prophylactic use of
      sympathomimetic drugs. The affect of combination of colloids and phenylephrine
      infusion on maternal hemodynamics has not been widely studied and there is no
      consensus about the dosage required and time of starting its administration.
      MATERIALS AND METHODS: This prospective, randomized, double-blind study enrolled
      90 healthy term parturients undergoing elective Cesarean delivery under lumbar
      subarachnoid block (0.5% hyperbaric bupivacaine 10 mg with fentanyl 25 MUg).
      Patients in Group A received prophylactic intravenous phenylephrine infusion (60
      MUg/minute) along with hydroxyl-ethyl-starch cohydration (6% HES 130/0.42;15
      ml/kg) immediately after subarachnoid block. In Group B, patients received 6% HES
      cohydration and intermittent intravenous 50 MUg boluses of phenylephrine. The
      efficacy of these in maintaining maternal SBP at 90-110% of baseline and neonatal
      well-being was evaluated. RESULTS: In Group B, 75.5% of patients required rescue
      phenylephrine boluses to maintain SBP while maternal hemodynamics were well
      maintained in Group A and rescue drug was not needed. Reactive hypertension
      occurred in one patient (2.2%) and bradycardia in two patients (4.4%) in Group A.
      Six patients complained of nausea in Group B (13.3%) compared to one in Group A.
      All the newborns had normal Apgar scores and Umbilical arterial pH > 7.2.
      CONCLUSION: A combination of colloid cohydration and prophylactic phenylephrine
      infusion initiated at 60 MUg/minute maintained maternal hemodynamics and neonatal
      well-being during Cesarean deliveries requiring minimum interventions by the
      anesthesiologist.

PMID- 24106362
TI  - Profile of infective microorganisms causing ventilator-associated pneumonia: A
      clinical study from resource limited intensive care unit.
AB  - BACKGROUND: Ventilator-associated pneumonia (VAP) is the most common cause of
      hospital acquired infection and death among patients admitted in ICU.
      Microorganisms responsible for VAP vary from place to place. Gram-negative
      bacteria (GNB) have emerged as a major group of pathogen causing VAP and over the
      years carbapenem group of antibiotics has emerged as one of the important
      antibiotics used in the critically ill patients. There have been reports of
      increased occurrence of infection by carbapenem-resistant bacteria in health care
      settings in recent times. AIM: The aim of the study was to assess the incidence
      of VAP, their microbiological profile with reference to carbapenemase producing
      GNB in the intensive care unit of a tertiary care hospital, their relation to
      initial emperical antibiotic therapy, sensitivity patterns, and outcome.
      MATERIALS AND METHODS: This prospective study was carried out over the period of
      1 year (July 2010-June 2011) on 100 randomly selected patients above the age of
      18 years admitted in the emergency/ICU and requiring intubation and mechanical
      ventilation for more than 72 hours. The diagnosis of VAP was established on the
      basis of clinical and radiological parameters as per Centre of Disease Centres
      (CDC) guidelines. A baseline sample was obtained after initial endotracheal
      intubation. Thereafter, the culture sent on the first day of occurrence of
      clinical sign of VAP. Culture was done on blood agar and MacConkey agar. All
      imipenem-resistant strains were further confirmed by Modified Hodge test and
      combined disc for confirmation of respective carbapenemase. RESULTS: Incidence of
      VAP was found to be 51%. GNB mainly Citrobacter 28 (52.83%) and Klebsiella
      pneumoniae 7 (13.21%), were the most commonly isolated pathogens. The prevalence
      of carbapenemase-producing GNB was alarmingly high 24/50 (48%). The entire
      carbapenemase producers showed high degree of cross resistance to antibiotics
      with some sensitivity to Polymyxin B (94 %) and Tigecycline (96%). CONCLUSION:
      High incidence of VAP and the potential carbapenemase-producing GNB are real
      threat in our ICU. The emergence of microorganisms known for its inherent
      resistance among most of the common first-line antibiotics calls for a alarm in
      all upcoming tertiary care hospitals.

PMID- 24106364
TI  - Communication skills of anesthesiologists: An Indian perspective.
AB  - BACKGROUND: Communication failure is a risk factor for mishaps and complaints,
      which can be reduced by effective communication between operating room team
      members and patients. AIM: To conduct a survey among anesthesiologists regarding
      communications skills and related issues like stress in case of communication
      failure, need for training, music in operation theater, and language barrier at
      their work place. MATERIALS AND METHODS: We conducted a survey among
      anesthesiologists coming for a neuroanesthesia conference in India (n = 110) in
      February 2011 by questionnaire sent by e-mail to them. RESULTS: The response rate
      was 61.8% (68/110). Majority (95.5%) of the respondents agreed that good verbal
      communication leads to better patient outcome, better handling of crisis and is
      important between surgeons and anesthesiologists (98.5%). A total of 86% of the
      anesthesiologists felt that failure of communication caused stress to them. The
      idea of communication by e-mail or phone text messages instead of verbal
      communications was discouraged by 65.2%. A total of 82% of respondents felt that
      training of communication skills should be mandatory for all medical personnel
      and 77.6% were interested in participating in such course. Language barrier at
      work place was seen as hurdle by 62.7% of the respondents. A total of 80% of
      respondents felt that playing music in operating theater is appropriate.
      CONCLUSION: Results of the survey highlight the need for effective communication
      in the operating room between team members and need for formal training to
      improve it.

PMID- 24106363
TI  - Internal jugular vein cannulation: A comparison of three techniques.
AB  - CONTEXT: Ultrasound-guided internal jugular vein (IJV) cannulation is known for
      increasing success rate and decreasing rate of complications. The ultrasound
      image can be used as a real time image during cannulation or to prelocate the IJV
      before attempting cannulation. AIMS: This study compares both the ultrasound
      guided technique with the classical anatomical landmark technique (central
      approach) for right IJV cannulation in terms of success rate, complications, and
      time for cannulation. SETTINGS AND DESIGN: A prospective, randomized,
      observational study was conducted at a tertiary care hospital. MATERIAL AND
      METHODS: One hundred twenty patients requiring IJV cannulation were included in
      this study and were randomly allocated in three groups. Number of attempts,
      success rate, venous access time, catheterization time, and complications were
      observed in each group. STATISTICAL ANALYSIS USED: Statistical analysis was
      performed using STATA-9 software. Demographic data were compared using one-way
      analysis of variance (ANOVA). Nonparametric data were compared using the Kruskall
      Wallis test, and multiple comparisons were done applying The Mann-Whitney test
      for individual pairs of groups. Nominal data were compared by applying the Chi
      square test and Fisher exact test. RESULTS: Successful cannulation (<=3 attempt)
      was achieved in 90.83% of patients without any statistical significant difference
      between the groups. Venous access time and catheterization time was found to be
      significantly less in both the ultrasound groups than the anatomical land mark
      group. Number of attempts and success in first attempt was similar between the
      groups. CONCLUSIONS: Both the ultrasound techniques are found to be better than
      the anatomical landmark technique. Further, ultrasound-guided prelocation was
      found to be as effective as ultrasound guided real-time imaging technique for
      right IJV cannulation.

PMID- 24106365
TI  - Accidental intravenous infusion of a large dose of magnesium sulphate during
      labor: A case report.
AB  - During labor and child delivery, a wide range of drugs are administered. Most of
      these medications are high-alert medications, which can cause significant harm to
      the patient due to its inadvertent use. Errors could be caused due to
      unfamiliarity with safe dosage ranges, confusion between similar looking drugs,
      mislabeling of drugs, equipment misuse, or malfunction and communication errors.
      We report a case of inadvertent infusion of a large dose of magnesium sulphate in
      a pregnant woman. 

PMID- 24106366
TI  - Giant oral tumor in a child with malnutrition and sickle cell trait: Anesthetic
      challenges.
AB  - Pediatric oral tumors have always been challenging for the even most skilled
      anesthesiologists. The conventional method of awake intubation is not realistic
      in this age group. The management is to chart out a plan to intubate the child
      post induction. We describe successful management of a case of giant of ossifying
      fibroma in a child with sickle cell trait where non-conventional innovate
      approach helped us to secure the airway pre-operatively and avoid possible
      medical complications. 

PMID- 24106367
TI  - Anesthetists approach in a neonate with nesidioblastoma undergoing
      pancreatectomy.
AB  - Persistent hyperinsulinemic hypoglycemia of infancy (PHHI) is rare, but an
      important cause of hypoglycemia in infants, associated with a number of
      structural abnormalities of the endocrine pancreas is collectively termed as
      "Islet cell dysmaturation syndrome." We present the anesthetic management in a
      clinically diagnosed case of PHHI in a 22 days old full term child, undergoing
      Subtotal Pancreatectomy. We have discussed the challenges faced in the intra
      operative period in managing this neonate for pancreatic resection surgery with
      focus on intra-operative management of blood glucose levels. 

PMID- 24106368
TI  - Lower segment cesarean section in a patient with severe thrombocytopenia and
      pregnancy induced hypertension.
AB  - Thrombocytopenia in pregnancy carries a major risk of feto-maternal morbidity and
      mortality. We present a case of hypocellular bone marrow with severe
      thrombocytopenia with pregnancy induced hypertension (PIH) for emergency lower
      segment cesarean section (LSCS). This disease is characterized by pancytopenia
      and hypocellular bone marrow with impaired morphology and maturation. Causes of
      death due to this disease include hemorrhage and infection secondary to
      thrombocytopenia and neutropenia especially following surgery. We report
      successful management of emergency LSCS with severe thrombocytopenia with severe
      PIH. 

PMID- 24106369
TI  - Epidermolysis bullosa: Careful monitoring and no touch principle for anesthesia
      management.
AB  - Epidermolysis bullosa (EB) is a rare genetic mechanobullous disorder, with
      excessive fragility of the skin and mucous membranes. Avoiding mechanical injury
      to the skin and mucous membranes is essential in the anesthetic management.
      Shearing forces applied to the skin result in bullae formation, while compressive
      forces to the skin are tolerated. The challenge is to use monitoring technology
      without damaging the epithelial surface. Difficult airway, positioning issues,
      nutritional deficiencies, poor immunity, and carcinogenic potential add to the
      comorbidities. We managed a child with EB undergoing syndactyly release. Ensuring
      maximal skin and mucous membrane protection, anesthesia in children with EB can
      be conducted with few sequelae. 

PMID- 24106370
TI  - Anesthesia for opioid addict: Challenges for perioperative physician.
AB  - Opioid addiction is on a rise globally. Such a patient presents to an
      anesthesiologist as well as to the surgeon with an array of challenges. We
      present the case of an opioid addict (pentazocine) who presented for debridement
      and grafting of eschars and old healed scars. Initially he was medically managed
      for opioid addiction followed by a planned anesthesia. We hereby discuss the
      challenges faced during perioperative period. 

PMID- 24106372
TI  - Difficulty in proseal laryngeal mask airway insertion: An unusual cause.

PMID- 24106371
TI  - Role of chest X-ray in citing central venous catheter tip: A few case reports
      with a brief review of the literature.
AB  - Central venous catheter (CVC) insertions are increasingly performed in surgical
      patients and intensive therapy. A simple and invasive procedure performed under
      strict sterile precautions with complications ranging from arrhythmias;
      infections; and life-threatening complications such as pericardial tamponade,
      cardiac perforation and even death. A post-procedure chest X-ray (CXR), though
      does not accurately assess the tip of the catheter in relation to the superior
      vena cava (SVC) and right atrium (RA), can detect malpositions, safety of
      catheter tip, pneumothorax and kinking. We would like to share some of the
      malpositions we encountered in our centre, their management and a brief review of
      the literature on optimal catheter tip location. 

PMID- 24106373
TI  - Sudden sustained asystole during a cerebellopontine angle surgery.

PMID- 24106374
TI  - The neural integrity monitor electromyogram tracheal tube: Anesthetic
      considerations.

PMID- 24106375
TI  - Is fibreoptic bronchoscopy a must prior to one lung ventilation in a situs
      inversus patient?

PMID- 24106376
TI  - Anesthetic management of T tube: A simple approach.

PMID- 24106377
TI  - Authors' reply: Anesthetic management of a patient with montgomery t-tube in-situ
      for direct laryngoscopy.

PMID- 24106378
TI  - Acute shoulder pain for holding the face mask: A complication of mask
      ventilation.

PMID- 24106379
TI  - Kinking of a patent flexometallic tube due to dislodgement of reinforcing
      spirals.

PMID- 24106380
TI  - Spinal accesory nerve blockade by local infiltration for central venous catheter
      insertion: An unusual occurrence.

PMID- 24106381
TI  - Epidural lipomatosis: A dilemma in interventional pain management for the use of
      epidural Steroids.

PMID- 24106382
TI  - Pneumothorax following ultrasound guided supraclavicular brachial plexus block.

PMID- 24106383
TI  - Authors' reply: Pneumothorax following ultrasound guided supraclavicular brachial
      plexus block.

PMID- 24106384
TI  - Intensive care unit psychosis a well known fact but rarely thought early.

PMID- 24106385
TI  - Can Klebsiella sepsis lead to hyperammonemic encephalopathy with normal liver
      function?

PMID- 24106386
TI  - Septic pulmonary embolism following necrotizing fasciitis of the upper limb.

PMID- 24106387
TI  - An indigenous minitracheostomy/cricothyroidotomy set developed from unused items
      from intra-aortic balloon pump kit.

PMID- 24106388
TI  - Amitraz: An unfamiliar poisoning with familiar pesticide.

PMID- 24106389
TI  - Mapping the antiplatelet effects of clopidogrel and aspirin by modified
      thromboelastography.

PMID- 24106390
TI  - Data acquisition from S/5 GE Datex anesthesia monitor using VSCapture: An open
      source.NET/Mono tool.

PMID- 24106391
TI  - Dental guards: An alternative solution for loose tooth.

PMID- 24106392
TI  - Is MOUTHS better than MOUTH?

PMID- 24106393
TI  - Intra-lingual succinylcholine for the treatment of adult laryngospasm in the
      absence of IV access.

PMID- 24106394
TI  - Medical influences, surgical outcomes: role of common medications on the risk of
      perforation from untreated diverticular disease.
AB  - Numerous drugs, largely used in the wards or at home, have a significant
      influence on patients with untreated diverticular disease. The consequences can
      be disastrous, may require an emergency operation, postoperative intensive care,
      and overall influence the patient's length of stay and the final outcomes.
      Bearing these considerations in mind the routine or chronic administration of
      pain-killers, steroids and non-steroidal anti-inflammatory should be balanced in
      patients with known diverticular disease as it normally happens with other
      conditions potentially affected by these drugs (i.e., peptic ulcer disease or
      chronic obstructive pulmonary disease). This is even more important in the old
      and frail patient where an eventual surgical treatment may not always be
      possible. 

PMID- 24106395
TI  - Liver transplantation in alcoholic liver disease current status and
      controversies.
AB  - Alcoholic cirrhosis remains the second most common indication for liver
      transplantation. A comprehensive medical and psychosocial evaluation is needed
      when making a decision to place such patients on the transplant list. Most
      transplant centers worldwide need a minimum of 6 mo of alcohol abstinence for
      listing these patients. Patients with alcohol dependence are at high risk for
      relapse to alcohol use after transplantation (recidivism). These patients need to
      be identified and require alcohol rehabilitation treatment before
      transplantation. Recidivism to the level of harmful drinking is reported in about
      15%-20% cases. Although, recurrent cirrhosis and graft loss from recidivism is
      rare, occurring in less than 5% of all alcoholic cirrhosis-related transplants,
      harmful drinking in the post-transplant period does impact the long-term outcome.
      The development of metabolic syndrome with cardiovascular events and de novo
      malignancy are important contributors to non liver-related mortality amongst
      transplants for alcoholic liver disease. Surveillance protocols for earlier
      detection of de novo malignancy are needed to improve the long-term outcome. The
      need for a minimum of 6 mo of abstinence before listing makes transplant a
      nonviable option for patients with severe alcoholic hepatitis who do not respond
      to corticosteroids. Emerging data from retrospective and prospective studies has
      challenged the 6 mo rule, and beneficial effects of liver transplantation have
      been reported in select patients with a first episode of severe alcoholic
      hepatitis who are unresponsive to steroids. 

PMID- 24106396
TI  - How reliable is current imaging in restaging rectal cancer after neoadjuvant
      therapy?
AB  - In patients with advanced rectal cancer, neoadjuvant chemo radiotherapy provides
      tumor downstaging and downsizing and complete pathological response in up to 30%
      of cases. After proctectomy complete pathological response is associated with low
      rates of local recurrence and excellent long term survival. Several authors claim
      a less invasive surgery or a non operative policy in patients with partial or
      clinical complete response respectively, however to identify patients with true
      complete pathological response before surgical resection remains a challenge.
      Current imaging techniques have been reported to be highly accurate in the
      primary staging of rectal cancer, however neoadjuvant therapy course produces
      deep modifications on cancer tissue and on surrounding structures such as
      overgrowth fibrosis, deep stroma alteration, wall thickness, muscle
      disarrangement, tumor necrosis, calcification, and inflammatory infiltration. As
      a result, the same imaging techniques, when used for restaging, are far less
      accurate. Local tumor extent may be overestimated or underestimated. The
      diagnostic accuracy of clinical examination, rectal ultrasound, computed
      tomography, magnetic resonance imaging, and positron emission tomography using
      18F-fluoro-2'-deoxy-D-glucose ranges between 25% and 75% being less than 60% in
      most studies, both for rectal wall invasion and for lymph nodes involvement. In
      particular the ability to predict complete pathological response, in order to
      tailor the surgical approach, remains low. Due to the radio-induced tissue
      modifications, combined with imaging technical aspects, low rate accuracy is
      achieved, making modern imaging techniques still unreliable in restaging rectal
      cancer after chemo-radiotherapy. 

PMID- 24106397
TI  - Probiotics and irritable bowel syndrome.
AB  - Irritable bowel syndrome (IBS) is common gastrointestinal problems. It is
      characterized by abdominal pain or discomfort, and is associated with changes in
      stool frequency and/or consistency. The etiopathogenesis of IBS may be
      multifactorial, as is the pathophysiology, which is attributed to alterations in
      gastrointestinal motility, visceral hypersensitivity, intestinal microbiota, gut
      epithelium and immune function, dysfunction of the brain-gut axis or certain
      psychosocial factors. Current therapeutic strategies are often unsatisfactory.
      There is now increasing evidence linking alterations in the gastrointestinal
      microbiota and IBS. Probiotics are living organisms which, when ingested in
      certain numbers, exert health benefits beyond inherent basic nutrition.
      Probiotics have numerous positive effects in the gastrointestinal tract.
      Recently, many studies have suggested that probiotics are effective in the
      treatment of IBS. The mechanisms of probiotics in IBS are very complex. The
      purpose of this review is to summarize the evidence and mechanisms for the use of
      probiotics in the treatment of IBS. 

PMID- 24106398
TI  - Tolerance and chimerism and allogeneic bone marrow/stem cell transplantation in
      liver transplantation.
AB  - The liver has particular tolerogenic properties that allow its spontaneous
      acceptance in some animal species. Liver structure is considered to favor a
      tolerogenic environment. The peripheral tolerance mechanisms also play a role in
      spontaneous tolerance to liver graft. In a clinical setting, the main challenge
      nowadays facing liver transplantation is minimization of immunosuppression with
      the goal of donor-specific tolerance. Mechanisms involved in tolerance to
      transplanted organs are complex and partly unknown. A significant mechanism in
      tolerance induction is chimerism. Chimerism can be induced through
      transplantation of allogeneic donor bone marrow/stem cells under appropriate host
      conditioning. This review focuses on the tolerance mechanisms in liver
      transplantation and highlights the role of chimerism and allogeneic bone
      marrow/stem cell transplantation in tolerance development. 

PMID- 24106399
TI  - Electroacupuncture improves gut barrier dysfunction in prolonged hemorrhagic
      shock rats through vagus anti-inflammatory mechanism.
AB  - AIM: To investigate whether electroacupuncture (EA) at Zusanli (ST36) prevents
      intestinal barrier and remote organ dysfunction following prolonged hemorrhagic
      shock through a vagus anti-inflammatory mechanism. METHODS: Sprague-Dawley rats
      were subjected to about 45% of total blood volume loss followed by delayed fluid
      replacement (DFR) with Ringer lactate 3h after hemorrhage. In a first study, rats
      were randomly divided into six groups: (1) EAN: EA at non-channel acupoints
      followed by DFR; (2) EA: EA at ST36 after hemorrhage followed by DFR; (3) VGX/EA:
      vagotomy (VGX) before EA at ST36 and DFR; (4) VGX/EAN: VGX before EAN and DFR;
      (5) alpha-bungarotoxin (alpha-BGT)/EA: intraperitoneal injection of alpha-BGT
      before hemorrhage, followed by EA at ST36 and DFR; and (6) alpha-BGT/EAN group:
      alpha-BGT injection before hemorrhage followed by EAN and DFR. Survival and mean
      arterial pressure (MAP) were monitored over the next 12 h. In a second study,
      with the same grouping and treatment, cytokine levels in plasma and intestine,
      organ parameters, gut injury score, gut permeability to 4 kDa FITC-dextran, and
      expression and distribution of tight junction protein ZO-1 were evaluated.
      RESULTS: MAP was significantly lowered after blood loss; EA at ST36 improved the
      blood pressure at corresponding time points 3 and 12 h after hemorrhage. EA at
      ST36 reduced tumor necrosis factor-alpha and interleukin (IL)-6 levels in both
      plasma and intestine homogenates after blood loss and DFR, while vagotomy or
      intraperitoneal injection of alpha-BGT before EA at ST36 reversed its anti
      inflammatory effects, and EA at ST36 did not influence IL-10 levels in plasma and
      intestine. EA at ST36 alleviated the injury of intestinal villus, the gut injury
      score being significantly lower than that of EAN group (1.85 +/- 0.33 vs 3.78 +/-
      0.59, P < 0.05). EA at ST36 decreased intestinal permeability to FITC-dextran
      compared with EAN group (856.95 ng/mL +/- 90.65 ng/mL vs 2305.62 ng/mL +/- 278.32
      ng/mL, P < 0.05). EA at ST36 significantly preserved ZO-1 protein expression and
      localization at 12 h after hemorrhage. However, EA at non-channel acupoints had
      no such effect, and abdominal vagotomy and alpha-BGT treatment could weaken or
      eliminate the effects of EA at ST36. Besides, EA at ST36 decreased blood
      aminotransferase, MB isoenzyme of creatine kinase and creatinine vs EAN group at
      corresponding time points. At the end of 12-h experiment, the survival rate of
      the EA group was significantly higher than that of the other groups. CONCLUSION:
      EA at ST36 attenuates the systemic inflammatory response, protects intestinal
      barrier integrity, improves organ function and survival rate after hemorrhagic
      shock via activating the cholinergic anti-inflammatory mechanism.

PMID- 24106400
TI  - Gastrointestinal stromal tumors of the duodenum: surgical management and survival
      results.
AB  - AIM: To provide long-term survival results of operable duodenal gastrointestinal
      stromal tumors (DGISTs) in a tertiary center in China. METHODS: In this
      retrospective study, the pathological data of 28 patients with DGISTs who had
      been treated surgically at the Second Department of General Surgery, Sir Run Run
      Shaw Hospital (SRRSH) from June 1998 to December 2006 were reviewed. All
      pathological slides were examined by a single pathologist to confirm the
      diagnosis. In patients whose diagnosis was not confirmed by immunohistochemistry
      at the time of resection, representative paraffin blocks were reassembled, and
      sections were studied using antibodies against CD117 (c-kit), CD34, smooth muscle
      actin (SMA), vimentin, S-100, actin (HHF35), and desmin. Operative procedures
      were classified as wedge resection (WR, local resection with pure closure,
      without duodenal transection or anastomosis), segmental resection [SR, duodenal
      transection with Roux-Y or Billroth II gastrojejunostomy (G-J), end-to-end
      duodenoduodenostomy (D-D), end-to-end or end-to-side duodenojejunostomy (D-J)],
      and pancreaticoduodenectomy (PD, Whipple operation with pancreatojejunostomy). R0
      resection was pursued in all cases, and at least R1 resection was achieved.
      Regional lymphadenectomy was not performed. Clinical manifestations, surgery,
      medical treatment and follow-up data were retrospectively analyzed. Related
      studies in the literature were reviewed. RESULTS: There were 12 males and 16
      females patients, with a median age of 53 years (20-76 years). Their major
      complaints were "gastrointestinal bleeding" (57.2%) and "nonspecific discomfort"
      (32.1%). About 14.3%, 60.7%, 17.9%, and 7.1% of the tumors originated in the
      first to fourth portion, respectively, with a median size of 5.8 cm (1.6-20 cm).
      Treatment was by WR in 5 cases (17.9%), SR in 13 cases (46.4%), and by PD in 10
      cases (35.7%). The morbidity and mortality rates were 35.7% and 3.6%,
      respectively. The median post-operative stay was 14.5 d (5-47 d). During a follow
      up of 61 (23-164) mo, the 2-year and 5-year relapse-free survival was 83.3% and
      50%, respectively. Eighty-four related articles were reviewed. CONCLUSION:
      Surgeons can choose to perform limited resection or PD for operable DGISTs if
      clear surgical margins are achieved. Comprehensive treatment is necessary.

PMID- 24106402
TI  - Disparities of conjugating protective enzyme activities in the colon of patients
      with adenomas and carcinomas.
AB  - AIM: To investigate the metabolic enzymatic capacity of the colon mucosa to
      detoxify noxious carcinogenic compounds. METHODS: We investigated the activity of
      2 conjugating enzymes-the microsomal uridine glucuronosyltransferase (UGT) and
      the cytosomal glutathione S-transferase (GST) in the uninvolved mucosa of the
      colon transversum and sigmoideum in patients with adenomatous polyps and
      colorectal cancer. Biopsies were taken from the mucosa during colonoscopies which
      were done for clinical (diagnostic) reasons. After storage, the biopsy material
      was homogenized and after differential centrifugation the enzyme assays were
      performed with 4-nitrophenol (UGT) and 1-chloro 2,4-dinitrobenzene (GST) as
      substrates. RESULTS: About 48 patients were included of which 28 had adenomas and
      20 had colorectal carcinomas confirmed by histopathology. Enzyme activities were
      expressed as nmol/mg per minute protein for the GST and as pmol/mg per minute
      protein for the UGT. Analysis of variance (F-test) indicated that both enzymes
      were more widely distributed in adenoma than in cancer patients. The means +/- SD
      were smaller for cancer patients: GST for adenomas 268 +/- 152 vs 241 +/- 69 for
      carcinomas and UGT for adenomas 197 +/- 200 vs 150 +/- 86 for carcinomas.
      CONCLUSION: Compared to patients with adenomatous colon polyps those with
      colorectal carcinoma exhibited a lower capacity of detoxifying enzyme metabolism
      and their activities clustered over a smaller range.

PMID- 24106401
TI  - Radiofrequency ablation for early oesophageal squamous neoplasia: outcomes form
      United Kingdom registry.
AB  - AIM: To report outcomes on patients undergoing radiofrequency ablation (RFA) for
      early oesophageal squamous neoplasia from a National Registry. METHODS: A
      Prospective cohort study from 8 tertiary referral centres in the United Kingdom.
      Patients with squamous high grade dysplasia (HGD) and early squamous cell
      carcinoma (ESCC) confined to the mucosa were treated. Visible lesions were
      removed by endoscopic mucosal resection (EMR) before RFA. Following initial RFA
      treatment, patients were followed up 3 monthly. Residual flat dysplasia was
      treated with RFA until complete reversal dysplasia (CR-D) was achieved or
      progression to invasive Squamous cell cancer defined as infiltration into the
      submucosa layer or beyond. The main outcome measures were CR-D at 12 mo from
      start of treatment, long term durability, progression to cancer and adverse
      events. RESULTS: Twenty patients with squamous HGD/ESCC completed treatment
      protocol. Five patients (25%) had EMR before starting RFA treatment. CR-D was 50%
      at 12 mo with a median of 1 RFA treatment, mean 1.5 (range 1-3). Two further
      patients achieved CR-D with repeat RFA after this time. Eighty per cent with CR-D
      remain dysplasia free at latest biopsy, with median follow up 24 mo (IQR 17-54).
      Six of 20 patients (30%) progressed to invasive cancer at 1 year. Four patients
      (20%) required endoscopic dilatations for symptomatic structuring after
      treatment. Two of these patients have required serial dilatations thereafter for
      symptomatic dysphagia with a median of 4 dilatations per patient. The other 2
      patients required only a single dilatation to achieve an adequate symptomatic
      response. One patient developed cancer during follow up after end of treatment
      protocol. CONCLUSION: The role of RFA in these patients remains unclear. In our
      series 50% patients responded at 12 mo. These figures are lower than limited
      published data.

PMID- 24106403
TI  - Endoscopic retrograde cholangiopancreatography with rendezvous cannulation
      reduces pancreatic injury.
AB  - AIM: To examine whether rendezvous endoscopic retrograde cholangiopancreatography
      (ERCP) is associated with less pancreatic damage, measured as leakage of
      proenzymes, than conventional ERCP. METHODS: Patients (n = 122) with symptomatic
      gallstone disease, intact papilla and no ongoing inflammation, were prospectively
      enrolled in this case-control designed study. Eighty-one patients were subjected
      to laparoscopic cholecystectomy and if intraoperative cholangiography suggested
      common bile duct stones (CBDS), rendezvous ERCP was performed intraoperatively (n
      = 40). Patients with a negative cholangiogram constituted the control group (n =
      41). Another 41 patients with CBDS, not subjected to surgery, underwent
      conventional ERCP. Pancreatic proenzymes, procarboxypeptidase B and trypsinogen-2
      levels in plasma, were analysed at 0, 4, 8 and 24 h. The proenzymes were
      determined in-house with a double-antibody enzyme linked immunosorbent assay.
      Pancreatic amylase was measured by an enzymatic colourimetric modular analyser
      with the manufacturer's reagents. All samples were blinded at analysis. RESULTS:
      Post ERCP pancreatitis (PEP) occurred in 3/41 (7%) of the patients cannulated
      with conventional ERCP and none in the rendezvous group. Increased serum levels
      indicating pancreatic leakage were significantly higher in the conventional ERCP
      group compared with the rendezvous ERCP group regarding pancreatic amylase levels
      in the 4- and 8-h samples (P = 0.0015; P = 0.03), procarboxypeptidase B in the 4-
      and 8-h samples (P < 0.0001; P < 0.0001) and trypsinogen-2 in the 24-hour samples
      (P = 0.03). No differences in these markers were observed in patients treated
      with rendezvous cannulation technique compared with patients that underwent
      cholecystectomy alone (control group). Post procedural concentrations of
      pancreatic amylase and procarboxypeptidase B were significantly correlated with
      pancreatic duct cannulation and opacification. CONCLUSION: Rendezvous ERCP
      reduces pancreatic enzyme leakage compared with conventional ERCP cannulation
      technique. Thus, laparo-endoscopic technique can be recommended with the ambition
      to minimise the risk for post ERCP pancreatitis.

PMID- 24106404
TI  - Outcomes of Roux-en-Y gastric bypass and laparoscopic adjustable gastric banding.
AB  - AIM: To evaluate weight loss and surgical outcomes of Roux-en-Y gastric bypass
      (RYGB) and laparoscopic adjustable gastric band (LAGB). METHODS: Data relating to
      changes in body mass index (BMI) and procedural complications after RYGB (1995
      2009; n = 609; 116M: 493F; 42.4 +/- 0.4 years) or LAGB (2004-2009; n = 686; 131M:
      555F; 37.2 +/- 0.4 years) were extracted from prospective databases. RESULTS: Pre
      operative BMI was higher in RYGB than LAGB patients (46.8 +/- 7.1 kg/m2 vs 40.4
      +/- 4.2 kg/m2, P < 001); more patients with BMI < 35 kg/m2 underwent LAGB than
      RYGB (17.1% vs 4.1%, P < 0.0001). BMI decrease was greater after RYGB. There were
      direct relationships between weight loss and pre-operative BMI (P < 0.001).
      Although there was no difference in weight loss between genders during the first
      3-year post-surgery, male LAGB patients had greater BMI reduction than females (
      8.2 +/- 4.3 kg/m2 vs -3.9 +/- 1.9 kg/m2, P = 0.02). Peri-operative complications
      occurred more frequently following RYGB than LAGB (8.0% vs 0.5%, P < 0.001);
      majority related to wound infection. LAGB had more long-term complications
      requiring corrective procedures than RYGB (8.9% vs 2.1%, P < 0.001). Conversion
      to RYGB resulted in greater BMI reduction (-9.5 +/- 3.8 kg/m2) compared to
      removal and replacement of the band (-6.0 +/- 3.0 kg/m2). Twelve months post
      surgery, fasting glucose, total cholesterol and low density lipoprotein levels
      were significantly lower with the magnitude of reduction greater in RYGB
      patients. CONCLUSION: RYGB produces substantially greater weight loss than LAGB.
      Whilst peri-operative complications are greater after RYGB, long-term
      complication rate is higher following LAGB.

PMID- 24106405
TI  - In vitro effect of amoxicillin and clarithromycin on the 3' region of cagA gene
      in Helicobacter pylori isolates.
AB  - AIM: To evaluate the in vitro effect of amoxicillin and clarithromycin on the cag
      pathogenicity island (cag PAI). METHODS: One hundred and forty-nine clinical
      isolates of Helicobacter pylori (H. pylori) cultured from gastric biopsies from
      206 Colombian patients with dyspeptic symptoms from a high-risk area for gastric
      cancer were included as study material. Antimicrobial susceptibility was
      determined by the agar dilution method. Resistant isolates at baseline and in
      amoxicillin and clarithromycin serial dilutions were subjected to genotyping
      (cagA, vacA alleles s and m), Glu-Pro-Ile-Tyr-Ala (EPIYA) polymerase chain
      reaction and random amplified polymorphic DNA (RAPD). Images of the RAPD
      amplicons were analyzed by Gel-Pro Analyzer 4.5 program. Cluster analyses was
      done using SPSS 15.0 statistical package, where each of the fingerprint bands
      were denoted as variables. Dendrograms were designed by following Ward's
      clustering method and the estimation of distances between each pair of H. pylori
      isolates was calculated with the squared Euclidean distance. RESULTS: Resistance
      rates were 4% for amoxicillin and 2.7% for clarithromycin with 2% double
      resistances. Genotyping evidenced a high prevalence of the genotype cagA
      positive/vacA s1m1. The 3' region of cagA gene was successfully amplified in
      92.3% (12/13) of the baseline resistant isolates and in 60% (36/60) of the
      resistant isolates growing in antibiotic dilutions. Upon observing the
      distribution of the number of EPIYA repetitions in each dilution with respect to
      baseline isolates, it was found that in 61.5% (8/13) of the baseline isolates, a
      change in the number of EPIYA repetitions lowered antibiotic pressure. The gain
      and loss of EPIYA motifs resulted in a diversity of H. pylori subclones after
      bacterial adjustment to changing conditions product of antibiotic pressure. RAPD
      PCR evidenced the close clonal relationship between baseline isolates and
      isolates growing in antibiotic dilutions. CONCLUSION: Antibiotic pressure does
      not induce loss of the cag pathogenicity island, but it can lead--in most cases-
      to genetic rearrangements within the 3' region cagA of the founding bacteria that
      can affect the level of tyrosine phosphorylation impacting on its cellular
      effects and lead to divergence of cagA-positive subclones.

PMID- 24106406
TI  - Liver metastasis is the only independent prognostic factor in AFP-producing
      gastric cancer.
AB  - AIM: To investigate differences between common gastric cancer and alpha
      fetoprotein (AFP)-producing gastric cancer according to the presence or absence
      of liver metastasis. METHODS: Between 1997 and 2011, 1299 patients underwent
      gastrectomy for gastric cancer (GC) at our institute and their hospital records
      were reviewed retrospectively. Patients were immunohistochemically divided into
      two groups: 23 patients (1.8%) with AFP-producing GC and 1276 patients (98.2%)
      without it. RESULTS: AFP-producing GC patients had a significantly higher
      incidence of deeper tumors, venous invasion, lymphatic invasion, lymph node
      metastasis, and liver metastasis and a poorer prognosis (P < 0.005) than those
      without AFP-producing GC. However, multivariate analysis revealed that AFP
      positivity was not an independent prognostic factor. The prognosis of AFP
      producing GC was similar to that of AFP-non producing GC according to the
      presence or absence of liver metastasis. Concerning recurrence, 47.8% of patients
      (11/23) with AFP-producing GC and 20.0% of patients (256/1276) without AFP
      producing GC exhibited recurrence. Liver metastasis [90.9% (10/11)] was the most
      prevalent in AFP-producing GC patients. Multivariate analysis revealed that liver
      metastasis was the only independent prognostic factor in AFP-producing GC (HR =
      17.6, 95%CI: 2.1-147.1; P = 0.0081). CONCLUSION: AFP-producing GC is similar to
      common GC without liver metastasis, which should be specifically targeted in an
      effort to improve the prognosis of AFP-producing GC patients.

PMID- 24106407
TI  - Clinical outcomes of radiation therapy for early-stage gastric mucosa-associated
      lymphoid tissue lymphoma.
AB  - AIM: To evaluate the clinical outcomes of radiation therapy (RT) for early-stage
      gastric mucosa-associated lymphoid tissue lymphoma (MALToma). METHODS: The
      records of 64 patients treated between 1998 and 2011 were analyzed
      retrospectively. For Helicobacter pylori (H. pylori)-positive patients (n = 31),
      chemotherapy or H. pylori eradication therapy was the initial treatment. In
      patients with failure after H. pylori eradication, RT was performed. For H.
      pylori-negative patients (n = 33), chemotherapy or RT was the first-line
      treatment. The median RT dose was 36 Gy. The target volume included the entire
      stomach and the perigastric lymph node area. RESULTS: All of the patients
      completed RT without interruption and showed complete remission on endoscopic
      biopsy after treatment. Over a median follow-up period of 39 mo, the 5-year local
      control rate was 89%. Salvage therapy was successful in all relapsed patients.
      Secondary malignancies developed in three patients. The 5-year overall survival
      rate was 94%. No patient presented symptoms of moderate-to-severe treatment
      related toxicities during or after RT. CONCLUSION: Radiotherapy results in
      favorable clinical outcomes in patients with early-stage gastric MALToma who
      experience failure of H. pylori eradication therapy and those who are H. pylori
      negative.

PMID- 24106408
TI  - Glycyrrhizinate reduces portal hypertension in isolated perfused rat livers with
      chronic hepatitis.
AB  - AIM: To investigate the effects of diammonium glycyrrhizinate (Gly) on portal
      hypertension (PHT) in isolated portal perfused rat liver (IPPRL) with carbon
      tetrachloride (CCl4)-induced chronic hepatitis. METHODS: PHT model was replicated
      with CCl4 in rats for 84 d. Model was identified by measuring the ascetic
      amounts, hepatic function, portal pressure in vivo, splenic index, and
      pathological alterations. Inducible nitric oxide synthase (iNOS) in liver was
      assessed by immunohistochemistry. IPPRLs were performed at d0, d28, d56, and d84.
      After phenylephrine-induced constriction, Gly was geometrically used to reduce
      PHT. Gly action was expressed as median effective concentration (EC50) and area
      under the curve (AUC). Underlying mechanism was exploited by linear correlation
      between AUC values of Gly and existed iNOS in portal triads. RESULTS: PHT model
      was confirmed with ascites, splenomegaly, serum biomarkers of hepatic injury, and
      elevated portal pressure. Pathological findings had shown normal hepatic
      structure at d0, degenerations at d28, fibrosis at d56, cirrhosis at d84 in PHT
      rats. Pseudo lobule ratios decreased and collagen ratios increased progressively
      along with PHT development. Gly does dose-dependently reduce PHT in IPPRLs with
      CCl4-induced chronic hepatitis. Gly potencies were increased gradually along with
      PHT development, characterized with its EC50 at 2.80 * 10-10, 3.03 * 10-11, 3.77
      * 10-11 and 4.65*10-11 mol/L at d0, d28, d56 and d84, respectively. Existed iNOS
      was located at hepatocyte at d0, stellate cells at d28, stellate cells and
      macrophages at d56, and macrophages in portal triads at d84. Macrophages
      infiltrated more into portal triads and expressed more iNOS along with PHT
      development. AUC values of Gly were positively correlated with existed iNOS
      levels in portal triads. CONCLUSION: Gly reduces indirectly PHT in IPPRL with
      CCl4-induced chronic hepatitis. The underlying mechanisms may relate to rescue NO
      bioavailability from macrophage-derived peroxynitrite in portal triads.

PMID- 24106409
TI  - Up-to-seven criteria for hepatocellular carcinoma liver transplantation: a single
      center analysis.
AB  - AIM: To detect whether the up-to-seven should be used as inclusion criteria for
      liver transplantation for hepatocellular carcinoma. METHODS: Between April 2002
      and July 2008, 220 hepatocellular carcinoma (HCC) patients who were diagnosed
      with HCC and underwent liver transplantation (LT) at our liver transplantation
      center were included. These patients were divided into three groups according to
      the characteristics of their tumors (tumor diameter, tumor number): the Milan
      criteria group (Group 1), the in up-to-seven group (Group 2) and the out up-to
      seven group (Group 3). Then, we compared long-term survival and tumor recurrence
      of these three groups. RESULTS: The baseline characteristics of transplant
      recipients were comparable among these three groups, except for the type of liver
      graft (deceased donor liver transplant or live donor liver transplantation).
      There were also no significant differences in the pre-operative alpha-fetoprotein
      level. The 1-, 3-, and 5-year overall survival and tumor-free survival rate for
      the Milan criteria group were 94.8%, 91.4%, 89.7% and 91.4%, 86.2%, and 86.2%
      respectively; in the up-to-seven criteria group, these rates were 87.8%, 77.8%,
      and 76.6% and 85.6%, 75.6%, and 75.6% respectively (P < 0.05). However, the
      advanced HCC patients' (in the group out of up-to-seven criteria) overall and
      tumor-free survival rates were much lower, at 75%, 53.3%, and 50% and 65.8%,
      42.5%, and 41.7%, respectively (P < 0.01). CONCLUSION: Considering that patients
      in the up-to-seven criteria group exhibited a considerable but lower survival
      rate compared with the Milan criteria group, the up-to-seven criteria should be
      used carefully and selectively.

PMID- 24106410
TI  - Overexpression of insulin-like growth factor-I receptor as a pertinent biomarker
      for hepatocytes malignant transformation.
AB  - AIM: To investigate the dynamic features of insulin-like growth factor-I receptor
      (IGF-IR) expression in rat hepatocarcinogenesis, and the relationship between IGF
      IR and hepatocytes malignant transformation at mRNA or protein level. METHODS:
      Hepatoma models were made by inducing with 2-fluorenylacetamide (2-FAA) on male
      Sprague-Dawley rats. Morphological changes of hepatocytes were observed by
      pathological Hematoxylin and eosin staining, the dynamic expressions of liver and
      serum IGF-IR were quantitatively analyzed by an enzyme-linked immunosorbent
      assay. The distribution of hepatic IGF-IR was located by immunohistochemistry.
      The fragments of IGF-IR gene were amplified by reverse transcription-polymerase
      chain reaction, and confirmed by sequencing. RESULTS: Rat hepatocytes after
      induced by 2-FAA were changed dynamically from granule-like degeneration,
      precancerous to hepatoma formation with the progressing increasing of hepatic
      mRNA or IGF-IR expression. The incidences of liver IGF-IR, IGF-IR mRNA, specific
      IGF-IR concentration (ng/mg wet liver), and serum IGF-IR level (ng/mL) were 0.0%,
      0.0%, 0.63 +/- 0.17, and 1.33 +/- 0.47 in the control; 50.0%, 61.1%, 0.65 +/-
      0.2, and 1.51 +/- 0.46 in the degeneration; 88.9%, 100%, 0.66 +/- 0.14, and 1.92
      +/- 0.29 in the precancerosis; and 100%, 100%, 0.96 +/- 0.09, and 2.43 +/- 0.57
      in the cancerous group, respectively. IGF-IR expression in the cancerous group
      was significantly higher (P < 0.01) than that in any of other groups at mRNA or
      protein level. The closely positive IGF-IR relationship was found between livers
      and sera (r = 0.91, t = 14.222, P < 0.01), respectively. CONCLUSION: IGF-IR
      expression may participate in rat hepatocarcinogenesis and its abnormality should
      be an early marker for hepatocytes malignant transformation.

PMID- 24106411
TI  - Endoscopic retrograde cholangiopancreatography and laparoscopic cholecystectomy
      during the same session: feasibility and safety.
AB  - AIM: To explore the feasibility and safety of endoscopic retrograde
      cholangiopancreatography and laparoscopic cholecystectomy (LC) performed during
      the same session. METHODS: Between July 2010 and May 2013, 156 patients with
      gallstones and common bile duct (CBD) stones were enrolled in this retrospective
      study. According to the sequence of endoscopic procedures and LC, patients were
      classified into two groups: in group 1, patients underwent endoscopic stone
      extraction and LC during the same session, and in group 2, patients underwent LC
      at least 3 d after endoscopic stone extraction. Outcomes of the endoscopic
      procedures and LC were compared between the two groups, respectively. RESULTS:
      There were 91 patients in group 1 and 65 patients in group 2. The characteristics
      of the two groups were similar. The mean duration of the endoscopic procedures
      was 34.9 min in group 1 and 35.3 min in group 2. There were no significant
      differences in the success rate of the endoscopic procedures (97.8% for group 1
      vs 98.5% for group 2), the total rate of endoscopic complications (4.40% for
      group 1 vs 4.62% for group 2) and CBD stone clearance rate (96.7% for group 1 vs
      96.9% for group 2). Duration of LC was 53.6 min in group 1 and 52.8 min in group
      2. There were no significant differences in the overall LC-related morbidity and
      postoperative hospital stay. CONCLUSION: Endoscopic stone extraction and LC
      performed during the same session was feasible and safe in patients with
      gallstones and concomitant CBD stones.

PMID- 24106413
TI  - Removal of an embedded "covered" biliary stent by the "stent-in-stent" technique.
AB  - A 46-year-old man was admitted with obstructive jaundice and cross-sectional
      imaging with computed tomography suggested distal biliary obstruction. A distal
      common bile duct stricture was found at endoscopic retrograde
      cholangiopancreatography (ERCP) and cytology was benign. A 6 cm fully covered
      self-expanding metal stent (SEMS) was inserted across the stricture to optimize
      biliary drainage. However, the SEMS could not be removed at repeat ERCP a few
      months later. A further fully covered SEMS was inserted within the existing stent
      to enable extraction and both stents were retrieved successfully a few weeks
      later. Fully covered biliary (SEMS) are used to treat benign biliary strictures.
      This is the first reported case of inability to remove a fully-covered biliary
      SEMS. Possible reasons for this include tissue hyperplasia and consequent
      overgrowth into the stent proximally, or chemical or mechanical damage to the
      polymer covering of the stent. Application of the stent-in-stent technique
      allowed successful retrieval of the initial stent. 

PMID- 24106412
TI  - Helicobacter pylori infection and esophageal cancer risk: an updated meta
      analysis.
AB  - AIM: To clarify the association between Helicobacter pylori (H. pylori) infection
      and the risk of esophageal carcinoma through a meta-analysis of published data.
      METHODS: Studies which reported the association between H. pylori infection and
      esophageal cancer published up to June 2013 were included. The odds ratios (ORs)
      and corresponding 95%CIs of H. pylori infection on esophageal cancer with respect
      to health control groups were evaluated. Data were extracted independently by two
      investigators and discrepancies were resolved by discussion with a third
      investigator. The statistical software, STATA (version 12.0), was applied to
      investigate heterogeneity among individual studies and to summarize the studies.
      A meta-analysis was performed using a fixed-effect or random-effect method,
      depending on the absence or presence of significant heterogeneity. RESULTS: No
      significant association between H. pylori infection and esophageal squamous cell
      carcinoma (ESCC) risk was found in the pooled overall population (OR = 0.97,
      95%CI: 0.76-1.24). However, significant associations between H. pylori infection
      and ESCC risk were found in Eastern subjects (OR = 0.66, 95%CI: 0.43-0.89).
      Similarly, cytotoxin-associated gene-A (CagA) positive strains of infection may
      decrease the risk of ESCC in Eastern subjects (OR = 0.77, 95%CI: 0.65-0.92),
      however, these associations were not statistically significant in Western
      subjects (OR = 1.26, 95%CI: 0.97-1.63). For esophageal adenocarcinoma (EAC) the
      summary OR for H. pylori infection and CagA positive strains of infection were
      0.59 (95%CI: 0.51-0.68) and 0.56 (95%CI: 0.45-0.70), respectively. CONCLUSION: H.
      pylori infection is associated with a decreased risk of ESCC in Eastern
      populations and a decreased risk of EAC in the overall population.

PMID- 24106414
TI  - Magnetic resonance venography and liver transplant complications.
AB  - Hepatic vein stenosis is a rare but serious complication following liver
      transplantation. Multiple modalities can be utilized to image the hepatic
      vasculature. Magnetic resonance venography (MRV) provides certain advantages over
      ultrasound, computed tomography angiography and digital subtraction venography.
      MRV utilizes the same imaging principles of magnetic resonance angiography in
      order to image the venous system. Blood pool contrast agents, specifically
      gadofosveset trisodium, allow for steady state imaging up to 1 h following
      injection, with improved visualisation of vital venous structures by utilising
      delayed steady state imaging. Additionally, the inherent physics properties of
      magnetic resonance imaging also provide excellent soft tissue detail and thus
      help define the extent of complications that often plague the post-liver
      transplant patient. This case report describes the use of gadofosveset trisodium
      in a patient with hepatic venous stenosis following liver transplantation.
      Initial venography failed to outline the stenoses and thus MRV using a blood pool
      contrast agent was utilised in order to delineate the anatomy and plan a
      therapeutic endovascular procedure. 

PMID- 24106415
TI  - Large symptomatic gastric diverticula: two case reports and a brief review of
      literature.
AB  - Gastric diverticula are rare and uncommon conditions. Most gastric diverticula
      are asymptomatic. When symptoms arise, they are most commonly upper abdominal
      pain, nausea and emesis, while dyspepsia and vomiting are less common.
      Occasionally, patients with gastric diverticula can have dramatic presentations
      related to massive bleeding or perforation. The diagnosis may be difficult, as
      symptoms can be caused by more common gastrointestinal pathologies and only
      aggravated by diverticula. The appropriate management of diverticula depends
      mainly on the symptom pattern and as well as diverticulum size. There is no
      specific therapeutic strategy for an asymptomatic diverticulum. Although some
      authors support conservative therapy with antacids, this provides only temporary
      symptom relief since it is not able to resolve the underlying pathology. Surgical
      resection is the mainstay of treatment when the diverticulum is large,
      symptomatic or complicated by bleeding, perforation or malignancy, with over two
      thirds of patients remaining symptom-free after surgery, while laparoscopic
      resection, combined with intraoperative endoscopy, is a safe and feasible
      approach with excellent outcomes. Here, we present two cases of uncommon large
      symptomatic gastric diverticula with a discussion of the cornerstones in
      management and report a minimally invasive solution, with a brief review of the
      literature. 

PMID- 24106416
TI  - Isolated right posterior bile duct injury following cholecystectomy: report of
      two cases.
AB  - Anatomic variations of the right biliary system are one of the most common risk
      factors for sectoral bile duct injury (BDI) during cholecystectomy. Isolated
      right posterior BDI may in particular be a challenge for both diagnosis and
      management. Herein we describe two cases of isolated right posterior sectoral BDI
      that took place during laparoscopic cholecystectomy. Despite effective external
      biliary drainage from the liver hilum in both cases, there was a persistent
      biliary leak observed which was not visible on endoscopic retrograde
      cholangiogram. Careful evaluation of images from both endoscopic and magnetic
      resonance cholangiograms revealed the diagnosis of an isolated right posterior
      sectoral BDI. These were treated with a delayed bisegmental (segments 6 and 7)
      liver resection and a Roux-en-Y hepaticojejunostomy respectively with good
      outcomes at 24 and 4 mo of follow-up. This paper discusses strategies for
      prevention of such injuries along with the diagnostic and therapeutic challenges
      it offers. 

PMID- 24106417
TI  - Biliary ascariasis in a bile duct stones-removed female patient.
AB  - Biliary ascariasis is a common problem in rural areas in China. The common
      presentations include biliary colic, acute cholangitis, obstructive jaundice,
      choledocholithiasis and acute cholecystitis. Here, we describe a case with
      biliary ascariasis two days after endoscopic sphincterotomy for
      choledocholithiasis. A living ascaris was successfully removed by endoscopic
      retrograde cholangiopancreatography. This case indicated that biliary ascariasis
      is not an uncommon complication of endoscopic sphincterotomy in some regions
      where ascariasis is epidemic. 

PMID- 24106418
TI  - Metachronous intracystic and intraductal papillary neoplasms of the biliary tree.
AB  - A 77-year-old woman complained of epigastralgia, and a tumor (5 cm in diameter)
      of the gallbladder neck was detected by image analysis. Following
      cholecystectomy, the tumor was pathologically diagnosed as intraductal papillary
      neoplasm (IPN), gastric type, with associated invasive carcinoma. About 10 mo
      later, intraluminal multiple masses (3 foci, up to 1.8 cm) were noted in the
      extrahepatic bile duct, and the resected specimen showed that all tumors had
      similar gross and microscopic features as seen in gallbladder IPN without
      invasion, and they were synchronous multiple lesions. This case showed a
      papillary tumor of the gallbladder of gastric phenotype, and confirmed that the
      gallbladder is a target of IPN in addition to the bile ducts. 

PMID- 24106419
TI  - Comparison of pregnancies between perinatally and sexually HIV-infected women: an
      observational study at an urban hospital.
AB  - As perinatally HIV-infected (PHIV) women reach reproductive age, there is an
      increasing number who become pregnant. This is a retrospective cohort study of
      HIV-infected women who delivered from June 2007 to July 2012 at our institution.
      Maternal demographics, HIV characteristics, and obstetric and neonatal outcomes
      were compared. 20 PHIV and 80 SHIV pregnancies were reviewed. The groups had
      similar CD4+ counts, prevalence of AIDS, and use of antiretrovirals (ARV) at
      initiation of obstetrical care. PHIV women were significantly more likely to be
      younger, have a detectable viral load (35% versus 74%, P < 0.01), and have HIV
      genotype resistance (40% versus 12%, P < 0.01) than the SHIV women. The median
      gestational age at delivery (38 weeks) and rates of obstetrical and neonatal
      complications were similar between the groups. While the overall rate of cesarean
      delivery (CD) was similar, the rates for CD due to HIV were higher in the PHIV
      group (64% versus 22%, P < 0.01). There was one case (5.3%) of mother-to-child
      transmission in the PHIV group versus two cases (2.6%) in the SHIV group. In our
      population, PHIV pregnant women have a higher rate of HIV-genotype resistance and
      higher rate of detectable viral load leading to a higher rate of CD secondary to
      HIV. 

PMID- 24106420
TI  - Preparation and characterization of 6-mercaptopurine-coated magnetite
      nanoparticles as a drug delivery system.
AB  - BACKGROUND: Iron oxide nanoparticles are of considerable interest because of
      their use in magnetic recording tape, ferrofluid, magnetic resonance imaging,
      drug delivery, and treatment of cancer. The specific morphology of nanoparticles
      confers an ability to load, carry, and release different types of drugs. METHODS
      AND RESULTS: We synthesized superparamagnetic nanoparticles containing pure iron
      oxide with a cubic inverse spinal structure. Fourier transform infrared spectra
      confirmed that these Fe3O4 nanoparticles could be successfully coated with active
      drug, and thermogravimetric and differential thermogravimetric analyses showed
      that the thermal stability of iron oxide nanoparticles coated with chitosan and 6
      mercaptopurine (FCMP) was markedly enhanced. The synthesized Fe3O4 nanoparticles
      and the FCMP nanocomposite were generally spherical, with an average diameter of
      9 nm and 19 nm, respectively. The release of 6-mercaptopurine from the FCMP
      nanocomposite was found to be sustained and governed by pseudo-second order
      kinetics. In order to improve drug loading and release behavior, we prepared a
      novel nanocomposite (FCMP-D), ie, Fe3O4 nanoparticles containing the same amounts
      of chitosan and 6-mercaptopurine but using a different solvent for the drug. The
      results for FCMP-D did not demonstrate "burst release" and the maximum percentage
      release of 6-mercaptopurine from the FCMP-D nanocomposite reached about 97.7% and
      55.4% within approximately 2,500 and 6,300 minutes when exposed to pH 4.8 and pH
      7.4 solutions, respectively. By MTT assay, the FCMP nanocomposite was shown not
      to be toxic to a normal mouse fibroblast cell line. CONCLUSION: Iron oxide coated
      with chitosan containing 6-mercaptopurine prepared using a coprecipitation method
      has the potential to be used as a controlled-release formulation. These
      nanoparticles may serve as an alternative drug delivery system for the treatment
      of cancer, with the added advantage of sparing healthy surrounding cells and
      tissue.

PMID- 24106421
TI  - Pulsed electromagnetic field therapy for management of osteoarthritis-related
      pain, stiffness and physical function: clinical experience in the elderly.
AB  - BACKGROUND: Pulsed electromagnetic field (PEMF) therapy has shown promising
      therapeutic effectiveness on bone- and cartilage-related pathologies, being also
      safe for management of knee osteoarthritis. AIM: The aim of this study was to
      investigate the clinical efficacy of a PEMF device for management of knee
      osteoarthritis in elderly patients. MATERIALS AND METHODS: A total of 33 patients
      were screened, and 28 patients, aged between 60 and 83 and affected by bilateral
      knee osteoarthritis, were enrolled in this study. They received PEMF therapy on
      the right leg for a total of three 30-minute sessions per week for a period of 6
      weeks, while the left leg did not receive any treatment and served as control. An
      intravenous drip containing ketoprofen, sodium clodronate, glucosamine sulfate,
      calcitonin, and ascorbic acid, for a total volume of 500 mL, was administered
      during PEMF therapy. At baseline and 3 months post-PEMF therapy, Visual Analog
      Scale (VAS) was used to assess knee pain and Western Ontario McMaster
      Universities Osteoarthritis Index (WOMAC) was used to measure knee pain,
      stiffness and physical function. RESULTS: Changes in VAS and WOMAC scores were
      calculated for both knees as baseline minus post-treatment. A two sample
      Student's t-test, comparing change in knee-related VAS pain for PEMF-treated leg
      (49.8 +/- 2.03) vs control leg (11 +/- 1.1), showed a significant difference in
      favor of PEMF therapy (P < 0.001). A two sample Student's t-test comparing change
      in knee-related WOMAC pain, stiffness, and physical function for PEMF-treated leg
      (8.5 +/- 0.4, 3.5 +/- 0.2, 38.5 +/- 2.08, respectively) vs control leg (2.6 +/-
      0.2; 1.6 +/- 0.1; 4.5 +/- 0.5 respectively), also showed a significant difference
      in favor of PEMF therapy (P < 0.001). No adverse reactions to therapy were
      observed. CONCLUSION: The present study shows that PEMF therapy improves pain,
      stiffness and physical function in elderly patients affected by knee
      osteoarthritis.

PMID- 24106422
TI  - Multidisciplinary intervention reducing readmissions in medical inpatients: a
      prospective, non-randomized study.
AB  - BACKGROUND: The purpose of this study was to examine whether a multidisciplinary
      intervention targeting drug-related problems, cognitive impairment, and discharge
      miscommunication could reduce readmissions in a general hospital population.
      METHODS: This prospective, non-randomized intervention study was carried out at
      the department of general internal medicine at a tertiary university hospital.
      Two hundred medical inpatients living in the community and aged over 60 years
      were included. Ninety-nine patients received interventions and 101 received
      standard care. Control/intervention allocation was determined by geographic
      selection. Interventions consisted of a comprehensive medication review, improved
      discharge planning, post-discharge telephone follow-up, and liaison with the
      patient's general practitioner. The main outcome measures recorded were
      readmissions and hospital nights 12 months after discharge. Separate analyses
      were made for 12-month survivors and from an intention-to-treat perspective.
      Comparative analyses were made between groups as well as within groups over time.
      RESULTS: After 12 months, survivors in the control group had 125 readmissions in
      total, compared with 58 in the intervention group (Mann-Whitney U test, P =
      0.02). For hospital nights, the numbers were 1,228 and 492, respectively (P =
      0.009). Yearly admissions had increased from the previous year in the control
      group from 77 to 125 (Wilcoxon signed-rank test, P = 0.002) and decreased from 75
      to 58 in the intervention group (P = 0.25). From the intention-to-treat
      perspective, the same general pattern was observed but was not significant (1,827
      versus 1,008 hospital nights, Mann-Whitney test, P = 0.054). CONCLUSION: A
      multidisciplinary approach, targeting several different areas, could
      substantially lower readmissions and hospital costs in a non-terminal general
      hospital population.

PMID- 24106423
TI  - Evidence for cognitive-behavioral strategies improving dyspnea and related
      distress in COPD.
AB  - BACKGROUND: Dyspnea is a complex, prevalent, and distressing symptom of chronic
      obstructive pulmonary disease (COPD) associated with decreased quality of life,
      significant disability, and increased mortality. It is a major reason for
      referral to pulmonary rehabilitation. METHODS: We reviewed 23 COPD studies to
      examine the evidence for the effectiveness of cognitive-behavioral strategies for
      relieving dyspnea in COPD. RESULTS: Preliminary evidence from randomized
      controlled trials exists to support cognitive- behavioral strategies, used with
      or without exercise, for relieving sensory and affective components of dyspnea in
      COPD. Small to moderate treatment effects for relieving dyspnea were noted for
      psychotherapy (effect size [ES] = 0.08-0.25 for intensity; 0.26-0.65 for mastery)
      and distractive auditory stimuli (ES = 0.08-0.33 for intensity; 0.09 to -0.61 for
      functional burden). Small to large dyspnea improvements resulted from yoga (ES =
      0.2-1.21 for intensity; 0.67 for distress; 0.07 for mastery; and -8.37 for
      functional burden); dyspnea self-management education with exercise (ES = -0.14
      to -1.15 for intensity; -0.62 to -0.69 for distress; 1.04 for mastery; 0.14-0.35
      for self-efficacy); and slow-breathing exercises (ES = -0.34 to -0.83 for
      intensity; -0.61 to -0.80 for distress; and 0.62 for self-efficacy). Cognitive
      behavioral interventions may relieve dyspnea in COPD by (1) decreasing
      sympathetic nerve activity, dynamic hyperinflation, and comorbid anxiety, and (2)
      promoting arterial oxygen saturation, myelinated vagus nerve activity, a greater
      exercise training effect, and neuroplasticity. CONCLUSION: While evidence is
      increasing, additional randomized controlled trials are needed to evaluate the
      effectiveness of psychosocial and self-management interventions in relieving
      dyspnea, in order to make them more available to patients and to endorse them in
      official COPD, dyspnea, and pulmonary rehabilitation practice guidelines. By
      relieving dyspnea and related anxiety, such interventions may promote adherence
      to exercise programs and adaptive lifestyle change.

PMID- 24106424
TI  - Synthesis and characterization of low-toxicity N-caprinoyl-N-trimethyl chitosan
      as self-assembled micelles carriers for osthole.
AB  - Novel amphiphilic chitosan derivatives (N-caprinoyl-N-trimethyl chitosan [CA
      TMC]) were synthesized by grafting the hydrophobic moiety caprinoyl (CA) and
      hydrophilic moiety trimethyl chitosan to prepare carriers with good compatibility
      for poorly soluble drugs. Based on self-assembly, CA-TMC can form micelles with
      sizes ranging from 136 nm to 212 nm. The critical aggregation concentration
      increased from 0.6 mg * L(-1) to 88 mg * L(-1) with decrease in the degree of CA
      substitution. Osthole (OST) could be easily encapsulated into the CA-TMC
      micelles. The highest entrapment efficiency and drug loading of OST-loaded CA-TMC
      micelles(OST/CA-TMC) were 79.1% and 19.1%, respectively. The antitumor efficacy
      results show that OST/CA-TMC micelles have significant antitumor activity on Hela
      and MCF-7 cells, with a 50% of cell growth inhibition (IC50) of 35.8 and 46.7
      MUg. mL(-1), respectively. Cell apoptosis was the main effect on cell death of
      Hela and MCF-7 cells after OST administration. The blank micelles did not affect
      apoptosis or cell death of Hela and MCF-7 cells. The fluorescence imaging results
      indicated that OST/CA-TMC micelles could be easily uptaken by Hela and MCF-7
      cells and could localize in the cell nuclei. These findings suggest that CA-TMC
      micelles are promising carriers for OST delivery in cancer therapy. 

PMID- 24106426
TI  - Branched polyethylenimine-grafted-carboxymethyl chitosan copolymer enhances the
      delivery of pDNA or siRNA in vitro and in vivo.
AB  - To generate a good carrier for gene transfection, O-carboxymethyl chitosan-graft
      branched polyethylenimine (OCMPEI) copolymers were synthesized by increasing the
      weight percentage of branched polyethylenimine conjugated to the carboxyl groups
      of O-carboxymethyl chitosan. These spherical polyplexes with plasmid
      deoxyribonucleic acid (pDNA) or small interfering ribonucleic acid (siRNA) had
      diameters of ~200-300 nm or ~10-25 nm, respectively, and displayed significant
      transfection efficiency in normal and tumor cells. In particular, expression of
      green fluorescent protein (GFP) following pDNA transfection was effectively
      suppressed by delivery of GFP-specific siRNA with the same copolymer. The
      optimized copolymer and polyplexes were nontoxic in vitro and in vivo. The use of
      endocytosis inhibitors to investigate the mechanisms of transfection of the
      polyplexes suggested the involvement of macropinocytosis. An in vivo study in
      mice showed excellent GFP expression in the lung, kidney, and liver. The results
      demonstrated that the OCMPEI copolymer prepared in this study is a promising
      carrier for in vitro and in vivo gene delivery applications.

PMID- 24106425
TI  - Fibrinogen and fibrin based micro and nano scaffolds incorporated with drugs,
      proteins, cells and genes for therapeutic biomedical applications.
AB  - Over the past two decades, many types of natural and synthetic polymer-based
      micro- and nanocarriers, with exciting properties and applications, have been
      developed for application in various types of tissue regeneration, including
      bone, cartilage, nerve, blood vessels, and skin. The development of suitable
      polymers scaffold designs to aid the repair of specific cell types have created
      diverse and important potentials in tissue restoration. Fibrinogen (Fbg)- and
      fibrin (Fbn)-based micro- and nanostructures can provide suitable natural matrix
      environments. Since these primary materials are abundantly available in blood as
      the main coagulation proteins, they can easily interact with damaged tissues and
      cells through native biochemical interactions. Fbg- and Fbn-based micro and
      nanostructures can also be consecutively furnished/or encapsulated and
      specifically delivered, with multiple growth factors, proteins, and stem cells,
      in structures designed to aid in specific phases of the tissue regeneration
      process. The present review has been carried out to demonstrate the progress made
      with micro and nanoscaffold applications and features a number of applications of
      Fbg- and Fbn-based carriers in the field of biomaterials, including the delivery
      of drugs, active biomolecules, cells, and genes, that have been effectively used
      in tissue engineering and regenerative medicine. 

PMID- 24106427
TI  - Self-aggregated nanoparticles based on amphiphilic poly(lactic acid)-grafted
      chitosan copolymer for ocular delivery of amphotericin B.
AB  - BACKGROUND: The purpose of this study was to develop a self-aggregated
      nanoparticulate vehicle using an amphiphilic poly(lactic acid)-grafted-chitosan
      (PLA-g-CS) copolymer and to evaluate its potential for ocular delivery of
      amphotericin B. METHODS: A PLA-g-CS copolymer was synthesized via a "protection
      graft-deprotection" procedure and its structure was confirmed by Fourier
      transform infrared spectroscopy, (1)H nuclear magnetic resonance, and X-ray
      diffraction spectra. Amphotericin B-loaded nanoparticles based on PLA-g-CS
      (AmB/PLA-g-CS) were prepared by the dialysis method and characterized for
      particle size, zeta potential, and encapsulation efficiency. Studies of these
      AmB/PLA-g-CS nanoparticles, including their mucoadhesive strength, drug release
      properties, antifungal activity, ocular irritation, ocular pharmacokinetics, and
      corneal penetration were performed in vitro and in vivo. RESULTS: Fourier
      transform infrared spectroscopy, (1)H nuclear magnetic resonance, and X-ray
      diffraction spectra showed that the PLA chains were successfully grafted onto
      chitosan molecules and that crystallization of chitosan was suppressed. The self
      aggregated PLA-g-CS nanoparticles had a core-shell structure with an average
      particle size of approximately 200 nm and zeta potentials higher than 30 mV.
      Amphotericin B was incorporated into the hydrophobic core of the nanoparticles
      with high encapsulation efficiency. Sustained drug release from the nanoparticles
      was observed in vitro. The ocular irritation study showed no sign of irritation
      after instillation of the PLA-g-CS nanoparticles into rabbit eyes. The minimal
      inhibitory concentration of the AmB/PLA-g-CS nanoparticles showed antifungal
      activity similar to that of free amphotericin B against Candida albicans. The in
      vivo ocular pharmacokinetic study suggested that the PLA-g-CS nanoparticles have
      the advantage of prolonging residence time at the ocular surface. The corneal
      penetration study showed that the PLA-g-CS nanoparticles could penetrate into the
      cornea. CONCLUSION: Our results suggest that this nanoparticulate vehicle based
      on a PLA-g-CS copolymer might be a promising system for effective ocular delivery
      of amphotericin B.

PMID- 24106428
TI  - Systematic review of clinical studies related to pork intake and metabolic
      syndrome or its components.
AB  - Globally, both the incidence of type 2 diabetes and the consumption of meat, in
      particular pork meat, have increased, concurrently. Processed meats have been
      associated with an increased risk for diabetes in observational studies.
      Therefore, it is important to understand the possible mechanisms of this
      association and the impact of meats from different species. The goal of this
      systematic review was to assess experimental human studies of the impact of pork
      intake compared with other protein sources on early markers for the development
      of diabetes, ie, insulin resistance, glucose intolerance, and the components of
      the metabolic syndrome. A systematic review was conducted searching PubMed and
      EMBASE and using the Cochrane and PRISMA guidelines. Eight studies were eligible
      and critically reviewed. Five studies were based on a single meal or single day
      exposure to pork, as compared with other sources of protein. The glucose-insulin
      response following the pork meals did not differ compared with beef, shrimp, or
      mixed sources of proteins. However, compared with eggs, ham (processed meat) led
      to a larger insulin response in nonobese subjects. Compared with whey, ham led to
      a smaller insulin response and a larger glucose response. These findings suggest
      possible mechanisms for the association between processed meat and the
      development of diabetes. Nonprocessed pork meats were not compared with eggs or
      whey. The three longer interventions (11 days to 6 months) did not show a
      significant impact of pork on the components of the metabolic syndrome, with the
      exception of a possible benefit on waist circumference and high-density
      lipoprotein cholesterol (one study each with significant limitations). Most of
      the findings are weak and there is a lack of solid evidence. The literature on
      the topic is limited and important research gaps are identified. Considering
      recent trends and projections for diabetes and pork intake, this is an important
      global public health question that requires more attention in order to provide
      improved evidence-based dietary recommendations. 

PMID- 24106429
TI  - Atazanavir-bilirubin interaction: a pharmacokinetic-pharmacodynamic model.
AB  - PURPOSE: The aim of this work was to analyze the atazanavir-bilirubin
      relationship, using a new mathematical approach to pharmacokinetic
      pharmacodynamic models, for competitive drug interactions based on Michaelis
      Menten equations. PATIENTS AND METHODS: Because atazanavir induces an increase of
      plasma bilirubin levels, in a concentration-dependent manner, we developed a
      mathematical model, based on increments of atazanavir and bilirubin
      concentrations at steady state, in HIV infected (HIV(+)) patients, and plotted
      the corresponding nomogram for detecting suboptimal atazanavir exposure. RESULTS:
      By applying the obtained model, the results indicate that an absolute value or an
      increment of bilirubin at steady state below 3.8 MUmol/L, are predictive of
      suboptimal atazanavir exposure and therapeutic failure. CONCLUSION: We have
      successfully implemented a new mathematical approach to pharmacokinetic
      pharmacodynamic model for atazanavir-bilirubin interaction. As a result, we found
      that bilirubin plasma levels constitute a good marker of exposure to atazanavir
      and of viral suppression.

PMID- 24106430
TI  - Eosinophilic esophagitis in brazilian pediatric patients.
AB  - We examined 11 pediatric patients with eosinophilic esophagitis with a tardy
      diagnosis. The symptoms were initially thought to be related to other diseases,
      leading to the use of inadequate therapeutic approaches. The patients were
      between 3 and 17 years old (mean 7.8 +/- 3.8 years), and 8 of the patients were
      male. Common symptoms included abdominal pain, regurgitation, difficulty in
      gaining weight, vomiting, dysphagia, and coughing. The mean age for the onset of
      symptoms was 4.3 +/- 2.9 years. Endoscopic findings included normal mucosa in
      five (45%) patients, thickening of the mucosa with longitudinal grooves in three
      (27%), erosive esophagitis in two (18%), and a whitish stippling in one (9%)
      patient. Treatment included the use of a topical corticosteroid for 10 patients.
      In eight (73%) cases, the treatment made the symptoms disappear. Ten patients
      underwent histopathological management after treatment, with a decrease in the
      number of eosinophils. 

PMID- 24106431
TI  - The consequence of stacking by Brazilian journals.

PMID- 24106432
TI  - Comment on: One window-period donation in two years of individual donor-nucleic
      acid test screening for hepatitis B, hepatitis C and human immunodeficiency
      virus.

PMID- 24106433
TI  - Dynamics of sickle cell disease as one of the determinants of quality of life.

PMID- 24106434
TI  - Comment on: "Temporal distribution of blood donations in three Brazilian blood
      centers and its repercussion on the blood supply".

PMID- 24106435
TI  - Difficult blood donor choices: dance, feast or donate blood?

PMID- 24106436
TI  - A novel strategy for the screening for platelet refractoriness: prospects and
      limitations.

PMID- 24106437
TI  - Predictors of central nervous system involvement in diffuse large B-cell
      lymphoma: a divining rod is wanted.

PMID- 24106438
TI  - Rational use of blood: how to do it?

PMID- 24106439
TI  - Human T lymphotropic virus types 1 and 2: a point of view.

PMID- 24106440
TI  - Sociodemographic aspects and quality of life of patients with sickle cell anemia.
AB  - BACKGROUND: Sickle cell anemia is a chronic inherited disease, widespread in the
      Brazilian population due to the high degree of miscegenation in the country.
      Despite the high prevalence, there are few studies describing the characteristics
      of patients and the impact of the disease on quality of life. OBJECTIVE: To
      describe the sociodemographic profile and the impact of the disease on the
      quality of life of sickle cell anemia patients. METHODS: Over 18-year-old
      patients with sickle cell anemia who attended meetings held by the Associacao
      Baiana de Portadores de Doencas Falciformes, an association for sickle cell
      anemia patients in Bahia, were interviewed. Sociodemographic data were collected
      and the generic the Medical Outcomes 36-Item Short-Form Health Survey (SF-36)
      questionnaire, which is used to assess quality of life, was applied. The analysis
      of the descriptive statistics was performed using the Statistics Program for the
      Social Sciences software. RESULTS: Thirty-two mostly female (65.6%) patients were
      interviewed. The mean age was 31.9 +/- 12.67 years, 50.0% considered themselves
      black, 68.8% did not work and 87.5% had per capita income below the poverty line
      (up to one and a half minimum wages). The SF-36 scores were: limitation by
      physical aspects 26.56, functional capacity 28.9, emotional aspects 30.20, social
      aspects, 50.0, pain 50.31, mental health 54.62, general health status 56.09 and
      vitality 56.71. This shows that the disease has a huge impact on the patients'
      quality of life. CONCLUSION: The disease interferes in the working capacity of
      individuals, who mostly have low incomes and impaired access to healthcare
      services and significantly impacts on their quality of life.

PMID- 24106442
TI  - Platelet antibody detection by flow cytometry: an effective method to evaluate
      and give transfusional support in platelet refractoriness.
AB  - BACKGROUND: Immune platelet refractoriness is mainly caused by human leukocyte
      antigen antibodies (80-90% of cases) and, to a lesser extent, by human platelet
      antigen antibodies. Refractoriness can be diagnosed by laboratory tests and
      patients should receive compatible platelet transfusions. A fast, effective and
      low cost antibody-screening method which detects platelet human
      leukocyte/platelet antigen antibodies is essential in the management of immune
      platelet refractoriness. OBJECTIVE: The aim of this study was to evaluate the
      efficiency of the flow cytometry platelet immunofluorescence test to screen for
      immune platelet refractoriness. METHODS: A group of prospective hematologic
      patients with clinically suspected platelet refractoriness treated in a referral
      center in Campinas, SP during July 2006 and July 2011 was enrolled in this study.
      Platelet antibodies were screened using the flow cytometry platelet
      immunofluorescence test. Anti-human leukocyte antigen antibodies were detected by
      commercially available methods. The sensitivity, specificity and predictive
      values of the immunofluorescence test were determined taking into account that
      the majority of antiplatelet antibodies presented human leukocyte antigen
      specificity. RESULTS: Seventy-six samples from 32 female and 38 male patients
      with a median age of 43.5 years (range: 5-84 years) were analyzed. The
      sensitivity of the test was 86.11% and specificity 75.00% with a positive
      predictive value of 75.61% and a negative predictive value of 85.71%. The
      accuracy of the method was 80.26%. CONCLUSION: This study shows that the flow
      cytometry platelet immunofluorescence test has a high correlation with the anti
      human leukocyte antigen antibodies. Despite a few limitations, the method seems
      to be efficient, fast and feasible as the initial screening for platelet antibody
      detection and a useful tool to crossmatch platelets for the transfusional support
      of patients with immune platelet refractoriness.

PMID- 24106441
TI  - Temporal distribution of blood donations in three Brazilian blood centers and its
      repercussion on the blood supply.
AB  - BACKGROUND: Seasonal distribution of blood donation hinders efforts to provide a
      safe and adequate blood supply leading to chronic and persistent shortages. This
      study examined whether holidays, geographical area and donation type (community
      versus replacement) has any impact on the fluctuation of donations. METHODS: The
      numbers of blood donations from 2007 through 2010 in three Brazilian Retrovirus
      Epidemiological Donor Study II (REDS-II) participating centers were analyzed
      according to the week of donation. The weeks were classified as holiday or non
      holiday. To compare donations performed during holiday versus non-holiday weeks,
      tabulations and descriptive statistics for weekly donations by blood center were
      examined and time series analysis was conducted. RESULTS: The average weekly
      number of donations varied according to the blood center and type of week. The
      average number of donations decreased significantly during Carnival and Christmas
      and increased during the Brazilian National Donor Week. The fluctuation was more
      pronounced in Recife and Belo Horizonte when compared to Sao Paulo and higher
      among community donors. CONCLUSION: National bank holidays affect the blood
      supply by reducing available blood donations. Blood banks should take into
      account these oscillations in order to plan local campaigns, aiming at
      maintaining the blood supply at acceptable levels.

PMID- 24106443
TI  - Secondary infiltration of the central nervous system in patients with diffuse
      large B-cell lymphoma.
AB  - OBJECTIVE: To investigate the incidence and risk factors of infiltration of the
      central nervous system after the initial treatment of diffuse large B-cell
      lymphoma in patients treated at Santa Casa de Misericordia de Sao Paulo. METHODS:
      A total of 133 patients treated for diffuse large B-cell lymphoma from January
      2001 to April 2008 were retrospectively analyzed in respect to the incidence and
      risk factors of secondary central nervous system involvement of lymphoma.
      Intrathecal prophylaxis was not a standard procedure for patients considered to
      be at risk. This analysis includes patients whether they received rituximab as
      first-line treatment or not. RESULTS: Nine of 133 (6.7%) patients developed
      central nervous system disease after a mean observation time of 29 months. The
      median time to relapse or progression was 7.9 months after diagnosis and all but
      one patient died despite the treatment administered. Twenty-six (19.5%) patients
      of this cohort received rituximab as first-line treatment and nine (7.1%)
      received intrathecal chemoprophylaxis. Of the nine patients that relapsed, seven
      (77.7%) had parenchymal central nervous system involvement; seven (77.7%) had
      stage III or IV disease; one (11.1%) had bone marrow involvement; two (22.2%) had
      received intrathecal chemoprophylaxis; and 3 (33.3%) had taken rituximab. In a
      multivariate analysis, the risk factors for this infiltration were being male,
      previous use of intrathecal chemotherapy and patients that were refractory to
      initial treatment. CONCLUSION: Central nervous system infiltration in this cohort
      is similar to that of previous reports in the literature. As this was a small
      cohort with a rare event, only three risk factors were important for this
      infiltration.

PMID- 24106444
TI  - Critical evaluation of justifications for the transfusion of red blood cells: the
      reality of a government emergency hospital.
AB  - BACKGROUND: Blood products and derivatives are indispensable resources in medical
      therapies. However, it is important to note that the number of donations is far
      from ideal. Despite constant campaign efforts, a deficit of 1 million units is
      expected by 2030. OBJECTIVES: To determine the adequacy of the indications for
      red blood cell transfusion in an emergency hospital in Alagoas. METHODS: This was
      a cross-sectional observational study conducted at the Alagoas Blood Center. Of a
      total of 2936 red blood cell transfusion requests in 2009, 334 were randomized
      and compared with transfusion parameters described in the literature (primary
      variable). After analysis, the transfusion requests were categorized as adequate,
      inadequate or inconclusive. This last group included all red blood cell
      transfusion requests with insufficient clinical information, rendering their
      classification as adequate or inadequate impossible. The secondary variable
      involved the reasons for red blood cell transfusion. A 95% confidence interval
      was used in the statistical analysis. RESULTS: Forty-seven (14.07%) requests were
      adequate and 30 (8.98%) were inadequate. Most of the requests were classified as
      inconclusive (76.94%). The main indications for transfusion were upper
      gastrointestinal bleeding (26.95%), anemia (46.71%), hypovolemia/hypovolemic
      shock (10.78%) and sepsis/septic shock (3.29%). CONCLUSION: It was not possible
      to reach a conclusion on the adequacy of the indication for transfusion in most
      of the cases. Therefore, it is important to adopt a transfusion protocol,
      rigorously analyze blood bank requests, to provide awareness campaigns on the
      rational use of blood and to implement strategies to use blood products more
      effectively.

PMID- 24106445
TI  - Prevalence of human T-cell lymphotropic virus types 1 and 2 in blood donors of
      the Caruaru Blood Center (Hemope).
AB  - BACKGROUND: There is difficulty in gathering data on the prevalence of human T
      cell lymphotropic virus in blood donors as confirmatory testing is not mandatory
      in Brazil. This suggests there may be an underreporting of the prevalence.
      OBJECTIVE: To estimate the prevalence of human T-cell lymphotropic virus types 1
      and 2 in donors of a blood bank in Caruaru, Brazil. METHODS: This was an
      observational, epidemiological, descriptive, longitudinal and retrospective study
      with information about the serology of donors of the Caruaru Blood Center,
      Fundacao de Hematologia e Hemoterapia de Pernambuco (Hemope) from May 2006 to
      December 2010. The data were analyzed using the Excel 2010 computer program
      (Microsoft Office((r))). RESULTS: Of 61,881 donors, 60 (0.096%) individuals were
      identified as potential carriers of human T-cell lymphotropic virus types 1 and
      2. Of these, 28 (0.045%) were positive and 32 (0.051%) had inconclusive results
      in the serological screening. Forty-five (0.072%) were retested; 17 were positive
      (0.027%) and 3 inconclusive (0.005%). After confirmatory tests, 8 were positive
      (0.013%). Six (75%) of the confirmed cases were women. CONCLUSION:
      Epidemiological surveys like this are very important in order to create campaigns
      to attract donors and reduce the costs of laboratory tests.

PMID- 24106446
TI  - Pain measurement as part of primary healthcare of adult patients with sickle cell
      disease.
AB  - OBJECTIVE: The aim of this exploratory, cross-sectional study was to evaluate
      pain in sickle cell disease patients and aspects related to primary healthcare.
      METHODS: Data were obtained through home interviews. The assessment instruments
      (body diagram, Numerical Pain Scale, McGill Pain Questionnaire) collected
      information on the underlying disease and on pain. Data were analyzed using the
      Statistical Package for Social Sciences program for Windows. Associations between
      the subgroups of sickle cell disease patients (hemoglobin SS, hemoglobin SC,
      sickle beta-thalassemia and others) and pain were analyzed using contingency
      tables and non-parametric tests of association (classic chi-square, Fisher's and
      Kruskal-Wallis) with a level of 5% (p-value < 0.05) being set for the rejection
      of the null hypothesis. RESULTS: Forty-seven over 18-year-old patients with
      sickle cell disease were evaluated. Most were black (78.7%) and female (59.6%)
      and the mean age was 30.1 years. The average number of bouts of pain annually was
      7.02; pain was predominantly reported by individuals with sickle cell anemia
      (hemoglobin SS). The intensity of pain (Numeric Pain Scale) was 5.5 and the
      quantitative index (McGill) was 35.9. This study also shows that patients
      presented a high frequency of moderately painful crises in their own homes.
      CONCLUSION: According to these facts, it is essential that pain related to sickle
      cell disease is properly identified, quantified, characterized and treated at the
      three levels of healthcare. In primary healthcare, accurate measurement of pain
      combined with better care may decrease acute painful episodes and consequently
      minimize tissue damage, thus improving the patient's overall health.

PMID- 24106447
TI  - The JAK2 gene as a protagonist in chronic myeloproliferative neoplasms.

PMID- 24106448
TI  - Importance of immune response genes in hemophilia A.
AB  - Hemophilia A is a disease caused by a deficiency of coagulation factor VIII
      resulting from genetic inheritance linked to chromosome X. One treatment option
      is the administration of plasma or recombinant FVIII. However, some patients
      develop inhibitors or antibodies against this factor. Inhibitors are
      alloantibodies that bind to the epitope of factor VIII causing it to be
      recognized by the immune system as a foreign peptide. This is the most serious
      complication in hemophilia patients in respect to replacement therapy. Some
      studies have suggested that genetic factors influence the development of factor
      VIII inhibitors such as ethnicity, family history, mutations in the factor VIII
      gene and in genes of the immune system. The aim of this study was to conduct a
      literature review to assess the influence of genetic factors of immune response
      genes, especially genes of the major histocompatibility complex and cytokines,
      which may be related to the development of factor VIII inhibitors in hemophilia A
      patients. Understanding these risk factors will help to determine future
      differential treatment in the control and prevention of the development of
      inhibitors. 

PMID- 24106449
TI  - Essential thrombocythemia: a rare disease in childhood.
AB  - Essential thrombocythemia is an acquired myeloproliferative disorder
      characterized by the proliferation of megakaryocytes in bone marrow, leading to a
      persistent increase in the number of circulating platelets and thus increasing
      the risk for thrombotic and hemorrhagic events. The disease features
      leukocytosis, splenomegaly, vascular occlusive events, hemorrhages and vasomotor
      disorders. The intricate mechanisms underlying the molecular pathogenesis of this
      disorder are not completely understood and are still a matter of discussion.
      Essential thrombocythemia is an extremely rare disorder during childhood. We
      report on a case of essential thrombocythemia in a child and discuss the
      diagnostic approach and treatment strategy. 

PMID- 24106450
TI  - Shwachman-Diamond syndrome: first molecular diagnosis in a Brazilian child.
AB  - Herein the first molecular diagnosis of a Brazilian child with Shwachman-Diamond
      Syndrome is reported. A 6-year-old boy was diagnosed with cystic fibrosis at the
      age of 15 months due to recurrent respiratory infections, diarrhea and
      therapeutic response to pancreatic enzymes. Three sweat tests were negative. At
      the age of 5 years, he began to experience pain in the lower limbs, laxity of
      joints, lameness and frequent falls. A radiological study revealed metaphyseal
      chondrodysplasia. A complete blood cell count showed leukopenia (leukocytes: 3.1
      3.5 x 10(3)/uL), neutropenia (segmented neutrophils: 15-22%), but normal
      hemoglobin, hematocrit and platelet count. A molecular study revealed biallelic
      mutations in the Shwachman-Bodian-Diamond Syndrome gene (183-184TA-CT K62X in
      exon 2 and a 258+2T-C transition) confirming the diagnosis of Shwachman-Diamond
      Syndrome. A non-pathologic, silent nucleotide A to G transition at position 201
      was also found in heterozygosis in the Shwachman-Bodian-Diamond Syndrome gene.
      This is the first report to describe a Brazilian child with molecular diagnosis
      of Shwachman-Diamond Syndrome, a rare autosomal recessive disorder characterized
      by exocrine pancreatic insufficiency, intermittent or persistent neutropenia and
      skeletal changes. Other characteristics include immune system, hepatic and
      cardiac changes and predisposition to leukemia. Recurrent bacterial, viral and
      fungal infections are common. The possibility of Shwachman-Diamond Syndrome
      should be kept in mind when investigating children with a diagnosis of cystic
      fibrosis and normal sweat tests. 

PMID- 24106451
TI  - Platelet satellitism.

PMID- 24106452
TI  - Spent mushroom waste as a media replacement for peat moss in Kai-Lan (Brassica
      oleracea var. Alboglabra) production.
AB  - Peat moss (PM) is the most widely used growing substrate for the pot culture. Due
      to diminishing availability and increasing price of PM, researchers are looking
      for viable alternatives for peat as a growth media component for potted plants. A
      pot study was conducted with a view to investigate the possibility of using spent
      mushroom waste (SMW) for Kai-lan (Brassica oleracea var. Alboglabra) production
      replacing peat moss (PM) in growth media. The treatments evaluated were 100% PM
      (control), 100% SMW, and mixtures of SMW and PM in different ratios like 1 : 1, 1
      : 2, and 2 : 1 (v/v) with/without NPK amendment. The experiment was arranged in a
      completely randomized design with five replications per treatment. Chemical
      properties like pH and salinity level (EC) of SMW were within the acceptable
      range of crop production but, nutrient content, especially nitrogen content was
      not enough to provide sufficient nutrition to plant for normal growth. Only PM
      (100%) and SMW and PM mixture in 1 : 1 ratio with NPK amendment performed equally
      in terms of Kai-lan growth. This study confirms the feasibility of replacing PM
      by SMW up to a maximum of 50% in the growth media and suggests that NPK
      supplementation from inorganic sources is to ensure a higher productivity of Kai
      lan. 

PMID- 24106454
TI  - Monitoring of civil infrastructures by interferometric radar: a review.
AB  - Ground-based radar interferometry is an increasingly popular technique for
      monitoring civil infrastructures. Many research groups, professionals, and
      companies have tested it in different operative scenarios, so it is time for a
      first systematic survey of the case studies reported in the literature. This
      review is addressed especially to the engineers and scientists interested to
      consider the applicability of the technique to their practice, so it is focused
      on the issues of the practical cases rather than on theory and principles, which
      are now well consolidated. 

PMID- 24106453
TI  - Plasma homocysteine is associated with increased oxidative stress and antioxidant
      enzyme activity in welders.
AB  - The purpose of this study was to examine the association of vitamin B6 status and
      plasma homocysteine with oxidative stress and antioxidant capacities in welders.
      Workers were divided into either the welding exposure group (n = 57) or the
      nonexposure controls (n = 42) based on whether they were employed as welders.
      There were no significant differences in vitamin B6 status and plasma
      homocysteine concentration between the welding exposure group and the nonexposure
      controls. The welding exposure group had significantly higher levels of oxidized
      low-density lipoprotein cholesterol and lower erythrocyte glutathione
      concentration and superoxide dismutase (SOD) activities when compared to
      nonexposure controls. Plasma pyridoxal 5'-phosphate concentration did not
      correlate with oxidative stress indicators or antioxidant capacities in either
      group. However, plasma homocysteine significantly correlated with total
      antioxidant capacity (TAC) (partial r(s) = -0.34, P < 0.05) and erythrocyte SOD
      activities (partial r(s) = 0.29, P < 0.05) after adjusting for potential
      confounders in the welding exposure group. In the welding exposure group,
      adequate vitamin B6 status was not associated with oxidative stress or
      antioxidant capacities. However, elevated plasma homocysteine seemed to be a
      major contributing factor to antioxidant capacities (TAC and erythrocyte SOD
      activities) in welders.

PMID- 24106455
TI  - Synthesis, Spectroscopic, and Biological Studies on New Zirconium(IV) Porphyrins
      with Axial Ligand.
AB  - A series of parasubstituted tetraphenylporphyrin zirconium(IV) salicylate
      complexes (SA/5-SSAZr(IV)RTPP, R = p-H, p-CH3, p-NO2, p-Cl, SA = salicylate, and
      5-SSA = 5-sulfosalicylate) have been synthesized, and the spectral properties of
      free base porphyrins, their corresponding metallated, and axially ligated
      zirconium(IV) porphyrin compounds were compared with each other. A detailed
      analysis of ultraviolet-visible (UV-vis), proton nulcear magnetic resonance ((1)H
      NMR) spectroscopy, infrared (IR) spectroscopy, and elemental analysis suggested
      the transformation from free base porphyrins to zirconium(IV) porphyrins. The
      ability of the metal in this complex for extra coordination of solvent molecules
      was confirmed by ESI-MS spectra. Besides the fluorescence, cyclic voltammetry,
      and thermogravimetric studies, the complexes were also screened for antimicrobial
      and anticancer activities. Among all the complexes, 5-SSAZr(p-NO2TPP) shows high
      antibacterial activity. 

PMID- 24106458
TI  - New Nordic Nutrition Recommendations are here.

PMID- 24106456
TI  - Population groups in dietary transition.
AB  - BACKGROUND: Little is known about the effects of dietary acculturation in
      minority groups in the Nordic countries, including immigrants from non-Western
      societies. METHODS: A search was performed in Medlin33e/PubMed and SweMed+ for
      articles published in 1990-2011. RESULTS: A total of 840 articles were
      identified, with a final 32 articles used to tabulate results which were included
      in the primary analysis. High rates of vitamin D deficiency (23 articles) were
      found in immigrants of non-Western origin; deficiency rates were very high among
      both pregnant and non-pregnant women, and also among children, with young
      children of immigrant parents showing 50 times higher risk for rickets when
      compared to children of indigenous parents. The risk of iron deficiency (two
      articles) was high among immigrant women, while the results were inconclusive
      regarding children. High rates of dental caries (seven articles) were found among
      pre-school and younger school children of immigrant origin, while the risk of
      caries was not as evident among older children. In a secondary analysis,
      including 48 articles (results not tabulated), overweight and obesity (14
      articles) were seen in many immigrant groups, resulting in a high prevalence of
      diabetes (2 review articles from a total of 14 original articles) and incidence
      of coronary heart disease (CHD; seven articles). For hypertension (three
      articles), dyslipidemia (four articles), and dietary patterns among immigrants
      (10 articles), the results were contradictory. CONCLUSIONS: Risk of vitamin D
      deficiency is alarmingly high in the Nordic countries among immigrants of non
      Western origin, especially among women. Dental caries is high among immigrant
      children aged 0-7 years due to a higher intake of sugary products. Overweight and
      obesity, associated with a higher risk of diabetes and CHD, are prevalent in many
      immigrant groups and need further attention.

PMID- 24106457
TI  - Vitamin D - a systematic literature review for the 5th edition of the Nordic
      Nutrition Recommendations.
AB  - BACKGROUND: The present literature review is part of the NNR5 project with the
      aim of reviewing and updating the scientific basis of the 4th edition of the
      Nordic Nutrition Recommendations (NNR) issued in 2004. OBJECTIVES: The overall
      aim was to review recent scientific data on the requirements and health effects
      of vitamin D and to report it to the NNR5 Working Group, who is responsible for
      updating the current dietary reference values valid in the Nordic countries.
      METHODS: The electronic databases MEDLINE and Swemed were searched. We formulated
      eight questions which were used for the search. The search terms related to
      vitamin D status and intake and different health outcomes as well as to the
      effect of different vitamin D sources on vitamin D status. The search was done in
      two batches, the first covering January 2000-March 2010 and the second March 2009
      February 2011. In the first search, we focused only on systematic literature
      reviews (SLRs) and in the second on SLRs and randomized control trials (RCTs)
      published after March 2009. Furthermore, we used snowballing for SLRs and IRCTs
      published between February 2011 and May 2012. The abstracts as well as the
      selected full-text papers were evaluated in pairs. RESULTS: We found 1,706
      studies in the two searches of which 28 studies were included in our review. We
      found 7 more by snowballing, thus 35 papers were included in total. Of these
      studies, 31 were SLRs and 4 were RCTs. The SLRs were generally of good or fair
      quality, whereas that of the included studies varied from good to poor. The
      heterogeneity of the studies included in the SLRs was large which made it
      difficult to interpret the results and provide single summary statements. One
      factor increasing the heterogeneity is the large variation in the assays used for
      assessing 25-hydroxyvitamin D concentration [25(OH)D], the marker of vitamin D
      status. The SLRs we have reviewed conclude that the evidence for a protective
      effect of vitamin D is only conclusive concerning bone health, total mortality
      and the risk of falling. Moreover, the effect was often only seen in persons with
      low basal 25(OH)D concentrations. In addition, most intervention studies leading
      to these conclusions report that intervention with vitamin D combined with
      calcium and not vitamin D alone gives these benefits. It was difficult to
      establish an optimal 25(OH)D concentration or vitamin D intake based on the SLRs,
      but there are evidence that a concentration of >=50 nmol/l could be optimal. The
      dose-response studies relating vitamin D intake (fortification and
      supplementation) to S-25(OH)D suggested that an intake of 1-2.5 ug/day will
      increase the serum concentration by 1-2 nmol/l but this is dependent on the basal
      concentration with a response being greater when the basal concentration is low.
      CONCLUSION: Data show that a S-25(OH)D concentration of 50 nmol/l would reflect a
      sufficient vitamin D status. Results from this review support that the
      recommendation in NNR 2004 needs to be re-evaluated and increased for all age
      groups beyond 2 years of age. We refer to the total intake from food as well as
      supplements, given minimal sun exposure. Limited sunshine, however, does not
      reflect the situation for the majority of the Nordic population in the
      summertime. It should also be emphasized that there are large differences in
      results depending on assay methods and laboratories measuring 25(OH)D, adding to
      the uncertainty of determining an appropriate target concentration. Moreover, the
      dose-response of vitamin D on serum 25(OH)D-concentrations is not well
      established and is dependent on the basal concentrations, sunshine exposure and
      dietary intake. We advise that these uncertainties should be taken into account
      when setting the final Nordic recommendations.

PMID- 24106459
TI  - Insights on the functional interactions between miRNAs and copy number variations
      in the aging brain.
AB  - MicroRNAs (miRNAs) are regulatory genetic elements that coordinate the expression
      of thousands of genes and play important roles in brain aging and
      neurodegeneration. DNA polymorphisms affecting miRNA biogenesis, dosage, and gene
      targeting may represent potentially functional variants. The consequences of
      single nucleotide polymorphisms affecting miRNA function were previously
      demonstrated by both experimental and computational methods. However, little is
      known about how copy number variations (CNVs) influence miRNA metabolism and
      regulatory networks. We discuss potential mechanisms of CNVs-mediated effects on
      miRNA function and regulation that might have consequences for brain aging. We
      argue that CNVs, which potentially can alter miRNA expression, regulation or
      target gene recognition, are possible functional variants and should be
      considered high priority candidates in genotype-phenotype mapping studies of
      brain-related disorders. 

PMID- 24106460
TI  - Identification and function of long non-coding RNA.
AB  - Long non-coding (lnc) RNAs are defined as non-protein coding RNAs distinct from
      housekeeping RNAs such as tRNAs, rRNAs, and snRNAs, and independent from small
      RNAs with specific molecular processing machinery such as micro- or piwi-RNAs.
      Recent studies of lncRNAs across different species have revealed a diverse
      population of RNA molecules of differing size and function. RNA sequencing
      studies suggest transcription throughout the genome, so there is a need to
      understand how sequence relates to functional and structural relationships
      amongst RNA molecules. Our synthesis of recent studies suggests that neither
      size, presence of a poly-A tail, splicing, direction of transcription, nor strand
      specificity are of importance to lncRNA function. Rather, relative genomic
      position in relation to a target is fundamentally important. In this review, we
      describe issues of key importance in functional assessment of lncRNA and how this
      might apply to lncRNAs important in neurodevelopment. 

PMID- 24106461
TI  - Spatiotemporal specificity of contrast adaptation in mouse primary visual cortex.
AB  - Prolonged viewing of high contrast gratings alters perceived stimulus contrast,
      and produces characteristic changes in the contrast response functions of neurons
      in the primary visual cortex (V1). This is referred to as contrast adaptation.
      Although contrast adaptation has been well-studied, its underlying neural
      mechanisms are not well-understood. Therefore, we investigated contrast
      adaptation in mouse V1 with the goal of establishing a quantitative description
      of this phenomenon in a genetically manipulable animal model. One interesting
      aspect of contrast adaptation that has been observed both perceptually and in
      single unit studies is its specificity for the spatial and temporal
      characteristics of the stimulus. Therefore, in the present work we determined if
      the magnitude of contrast adaptation in mouse V1 neurons was dependent on the
      spatial frequency and temporal frequency of the adapting grating. We used
      protocols that were readily comparable with previous studies in cats and
      primates, and also a novel contrast ramp stimulus that characterized the spatial
      and temporal specificity of contrast adaptation simultaneously. Similar to
      previous work in higher mammals, we found that contrast adaptation was strongest
      when the spatial frequency and temporal frequency of the adapting grating matched
      the test stimulus. This suggests similar mechanisms underlying contrast
      adaptation across animal models and indicates that the rapidly advancing genetic
      tools available in mice could be used to provide insights into this phenomenon. 

PMID- 24106462
TI  - Delta-mediated cross-frequency coupling organizes oscillatory activity across the
      rat cortico-basal ganglia network.
AB  - The brain's ability to integrate different behavioral and cognitive processes
      relies on its capacity to generate neural oscillations in a cooperative and
      coordinated manner. Cross-frequency coupling (CFC) has recently been proposed as
      one of the mechanisms involved in organizing brain activity. Here we investigated
      the phase-to-amplitude CFC (PA-CFC) patterns of the oscillatory activity in the
      cortico-basal ganglia network of healthy, freely moving rats. Within-structure
      analysis detected consistent PA-CFC patterns in the four regions analyzed, with
      the phase of delta waves modulating the amplitude of activity in the gamma (low
      gamma ~50 Hz; high-gamma ~80 Hz) and high frequency ranges (high frequency
      oscillations HFO, ~150 Hz). Between-structure analysis revealed that the phase of
      delta waves parses the occurrence of transient episodes of coherence in the gamma
      and high frequency bands across the entire network, providing temporal windows of
      coherence between different structures. Significantly, this specific spatio
      temporal organization was affected by the action of dopaminergic drugs. Taken
      together, our findings suggest that delta-mediated PA-CFC plays a key role in the
      organization of local and distant activities in the rat cortico-basal ganglia
      network by fine-tuning the timing of synchronization events across different
      structures. 

PMID- 24106463
TI  - Opposite modulation of brain stimulation reward by NMDA and AMPA receptors in the
      ventral tegmental area.
AB  - Previous studies have shown that blockade of ventral tegmental area (VTA)
      glutamate N-Methyl-D-Aspartate (NMDA) receptors induces reward, stimulates
      forward locomotion and enhances brain stimulation reward. Glutamate induces two
      types of excitatory response on VTA neurons, a fast and short lasting
      depolarization mediated by alpha-amino-3-hydroxy-5-methyl-4-isoxazole propionate
      (AMPA) receptors and a longer lasting depolarization mediated by NMDA receptors.
      A role for the two glutamate receptors in modulation of VTA neuronal activity is
      evidenced by the functional change in AMPA and NMDA synaptic responses that
      result from repeated exposure to reward. Since both receptors contribute to the
      action of glutamate on VTA neuronal activity, we studied the effects of VTA AMPA
      and NMDA receptor blockade on reward induced by electrical brain stimulation.
      Experiments were performed on rats trained to self-administer electrical pulses
      in the medial posterior mesencephalon. Reward thresholds were measured with the
      curve-shift paradigm before and for 2 h after bilateral VTA microinjections of
      the AMPA antagonist, NBQX (2,3,-Dioxo-6-nitro-1,2,3,4
      tetrahydrobenzo(f)quinoxaline-7-sulfonamide, 0, 80, and 800 pmol/0.5 MUl/side)
      and of a single dose (0.825 nmol/0.5 MUl/side) of the NMDA antagonist, PPPA
      (2R,4S)-4-(3-Phosphonopropyl)-2-piperidinecarboxylic acid). NBQX produced a dose
      dependent increase in reward threshold with no significant change in maximum rate
      of responding. Whereas PPPA injected at the same VTA sites produced a significant
      time dependent decrease in reward threshold and increase in maximum rate of
      responding. We found a negative correlation between the magnitude of the
      attenuation effect of NBQX and the enhancement effect of PPPA; moreover, NBQX and
      PPPA were most effective when injected, respectively, into the anterior and
      posterior VTA. These results suggest that glutamate acts on different receptor
      sub-types, most likely located on different VTA neurons, to modulate reward. 

PMID- 24106464
TI  - Representations of pitch and slow modulation in auditory cortex.
AB  - Iterated ripple noise (IRN) is a type of pitch-evoking stimulus that is commonly
      used in neuroimaging studies of pitch processing. When contrasted with a
      spectrally matched Gaussian noise, it is known to produce a consistent response
      in a region of auditory cortex that includes an area antero-lateral to the
      primary auditory fields (lateral Heschl's gyrus). The IRN-related response has
      often been attributed to pitch, although recent evidence suggests that it is more
      likely driven by slowly varying spectro-temporal modulations not related to
      pitch. The present functional magnetic resonance imaging (fMRI) study showed that
      both pitch-related temporal regularity and slow modulations elicited a
      significantly greater response than a baseline Gaussian noise in an area that has
      been pre-defined as pitch-responsive. The region was sensitive to both pitch
      salience and slow modulation salience. The responses to pitch and spectro
      temporal modulations interacted in a saturating manner, suggesting that there may
      be an overlap in the populations of neurons coding these features. However, the
      interaction may have been influenced by the fact that the two pitch stimuli used
      (IRN and unresolved harmonic complexes) differed in terms of pitch salience.
      Finally, the results support previous findings suggesting that the cortical
      response to IRN is driven in part by slow modulations, not by pitch. 

PMID- 24106465
TI  - New evidence for the cerebellar involvement in personality traits.
AB  - Following the recognition of its role in sensory-motor coordination and learning,
      the cerebellum has been involved in cognitive, emotional, and even personality
      domains. This study investigated the relationships between cerebellar macro- and
      micro-structural variations and temperamental traits measured by Temperament and
      Character Inventory (TCI). High resolution T1-weighted, and Diffusion Tensor
      Images of 100 healthy subjects aged 18-59 years were acquired by 3 Tesla Magnetic
      Resonance scanner. In multiple regression analyses, cerebellar Gray Matter (GM)
      or White Matter (WM) volumes, GM Mean Diffusivity (MD), and WM Fractional
      Anisotropy (FA) were used as dependent variables, TCI scores as regressors,
      gender, age, and education years as covariates. Novelty Seeking scores were
      associated positively with the cerebellar GM volumes and FA, and negatively with
      MD. No significant association between Harm Avoidance, Reward Dependence or
      Persistence scores and cerebellar structural measures was found. The present data
      put toward a cerebellar involvement in the management of novelty. 

PMID- 24106466
TI  - Contextual exploration previous to an aversive event predicts long-term emotional
      consequences of severe stress.
AB  - Traumatic stress can lead to long-term emotional alterations, which may result in
      Posttraumatic Stress Disorder (PTSD). Fear reactions triggered by conditioned
      cues and exacerbated emotional arousal in face of non-conditioned stimuli are
      among the most prominent features of PTSD. We hypothesized that long-term
      emotional alterations seen in PTSD may depend on the strength of context-trauma
      association. Here, we investigated the contribution of previous contextual
      exploration to the long-term emotional outcomes of an intense foot shock in rats.
      We exposed male Wistar rats to a highly stressful event (foot shock, 2 mA, 1 sec)
      allowing them to explore or not the chamber prior to trauma. We, then, evaluated
      the long-term effects on emotionality. Fear was assessed by the time spent in
      freezing behavior either upon re-exposure to trauma context or upon exposure to
      an unknown environment made potentially more aversive by presentation of an
      acoustic stimulus. Behaviors on the elevated-plus-maze and acoustic startle
      response were also assessed. The possibility to explore the environment
      immediately before the aversive event led to differential long-term emotional
      effects, including a heightened freezing response to re-exposure to context,
      blunted exploratory behavior, fear sensitization and exacerbation of the acoustic
      startle response, in contrast to the minor outcomes of the foot shock with no
      prior context exploration. The data showed the strong contribution of contextual
      learning to long-term behavioral effects of traumatic stress. We argue that
      contextual representation contributes to the robust long-term behavioral
      alterations seen in this model of traumatic stress. 

PMID- 24106467
TI  - Social motor coordination in unaffected relatives of schizophrenia patients: a
      potential intermediate phenotype.
AB  - Intermediate endophenotypes emerge as an important concept in the study of
      schizophrenia. Although research on phenotypes mainly investigated cognitive,
      metabolic or neurophysiological markers so far, some authors also examined the
      motor behavior anomalies as a potential trait-marker of the disease. However, no
      research has investigated social motor coordination despite the possible
      importance of its anomalies in schizophrenia. The aim of this study was thus to
      determine whether coordination modifications previously demonstrated in
      schizophrenia are trait-markers that might be associated with the risk for this
      pathology. Interpersonal motor coordination in 27 unaffected first-degree
      relatives of schizophrenia patients and 27 healthy controls was assessed using a
      hand-held pendulum task to examine the presence of interpersonal coordination
      impairments in individuals at risk for the disorder. Measures of neurologic soft
      signs, clinical variables and neurocognitive functions were collected to assess
      the cognitive and clinical correlates of social coordination impairments in at
      risk relatives. After controlling for potential confounding variables, unaffected
      relatives of schizophrenia patients had impaired intentional interpersonal
      coordination compared to healthy controls while unintentional interpersonal
      coordination was preserved. More specifically, in intentional coordination, the
      unaffected relatives of schizophrenia patients exhibited coordination patterns
      that had greater variability and in which relatives did not lead the
      coordination. These results show that unaffected relatives of schizophrenia
      patients, like the patients themselves, also present deficits in intentional
      interpersonal coordination. For the first time, these results suggest that
      intentional interpersonal coordination impairments might be a potential motor
      intermediate endophenotype of schizophrenia opening new perspectives for early
      diagnosis. 

PMID- 24106468
TI  - Right inferior frontal gyrus activation as a neural marker of successful lying.
AB  - There is evidence to suggest that successful lying necessitates cognitive effort.
      We tested this hypothesis by instructing participants to lie or tell the truth
      under conditions of high and low working memory (WM) load. The task required
      participants to register a response on 80 trials of identical structure within a
      2 (WM Load: high, low) * 2 (Instruction: truth or lie) repeated-measures design.
      Participants were less accurate and responded more slowly when WM load was high,
      and also when they lied. High WM load activated the fronto-parietal WM network
      including dorsolateral prefrontal cortex (PFC), middle frontal gyrus, precuneus,
      and intraparietal cortex. Lying activated areas previously shown to underlie
      deception, including middle and superior frontal gyrus and precuneus. Critically,
      successful lying in the high vs. low WM load condition was associated with longer
      response latency, and it activated the right inferior frontal gyrus-a key brain
      region regulating inhibition. The same pattern of activation in the inferior
      frontal gyrus was absent when participants told the truth. These findings
      demonstrate that lying under high cognitive load places a burden on inhibition,
      and that the right inferior frontal gyrus may provide a neural marker for
      successful lying. 

PMID- 24106469
TI  - Scene perception in posterior cortical atrophy: categorization, description and
      fixation patterns.
AB  - Partial or complete Balint's syndrome is a core feature of the clinico
      radiological syndrome of posterior cortical atrophy (PCA), in which individuals
      experience a progressive deterioration of cortical vision. Although multi-object
      arrays are frequently used to detect simultanagnosia in the clinical assessment
      and diagnosis of PCA, to date there have been no group studies of scene
      perception in patients with the syndrome. The current study involved three linked
      experiments conducted in PCA patients and healthy controls. Experiment 1
      evaluated the accuracy and latency of complex scene perception relative to
      individual faces and objects (color and grayscale) using a categorization
      paradigm. PCA patients were both less accurate (faces < scenes < objects) and
      slower (scenes < objects < faces) than controls on all categories, with
      performance strongly associated with their level of basic visual processing
      impairment; patients also showed a small advantage for color over grayscale
      stimuli. Experiment 2 involved free description of real world scenes. PCA
      patients generated fewer features and more misperceptions than controls, though
      perceptual errors were always consistent with the patient's global understanding
      of the scene (whether correct or not). Experiment 3 used eye tracking measures to
      compare patient and control eye movements over initial and subsequent fixations
      of scenes. Patients' fixation patterns were significantly different to those of
      young and age-matched controls, with comparable group differences for both
      initial and subsequent fixations. Overall, these findings describe the
      variability in everyday scene perception exhibited by individuals with PCA, and
      indicate the importance of exposure duration in the perception of complex scenes.

PMID- 24106470
TI  - Mapping a lateralization gradient within the ventral stream for auditory speech
      perception.
AB  - Recent models on speech perception propose a dual-stream processing network, with
      a dorsal stream, extending from the posterior temporal lobe of the left
      hemisphere through inferior parietal areas into the left inferior frontal gyrus,
      and a ventral stream that is assumed to originate in the primary auditory cortex
      in the upper posterior part of the temporal lobe and to extend toward the
      anterior part of the temporal lobe, where it may connect to the ventral part of
      the inferior frontal gyrus. This article describes and reviews the results from a
      series of complementary functional magnetic resonance imaging studies that aimed
      to trace the hierarchical processing network for speech comprehension within the
      left and right hemisphere with a particular focus on the temporal lobe and the
      ventral stream. As hypothesized, the results demonstrate a bilateral involvement
      of the temporal lobes in the processing of speech signals. However, an increasing
      leftward asymmetry was detected from auditory-phonetic to lexico-semantic
      processing and along the posterior-anterior axis, thus forming a "lateralization"
      gradient. This increasing leftward lateralization was particularly evident for
      the left superior temporal sulcus and more anterior parts of the temporal lobe. 

PMID- 24106471
TI  - Exploring the brains of Baduk (Go) experts: gray matter morphometry, resting
      state functional connectivity, and graph theoretical analysis.
AB  - One major characteristic of experts is intuitive judgment, which is an automatic
      process whereby patterns stored in memory through long-term training are
      recognized. Indeed, long-term training may influence brain structure and
      function. A recent study revealed that chess experts at rest showed differences
      in structure and functional connectivity (FC) in the head of caudate, which is
      associated with rapid best next-move generation. However, less is known about the
      structure and function of the brains of Baduk experts (BEs) compared with those
      of experts in other strategy games. Therefore, we performed voxel-based
      morphometry (VBM) and FC analyses in BEs to investigate structural brain
      differences and to clarify the influence of these differences on functional
      interactions. We also conducted graph theoretical analysis (GTA) to explore the
      topological organization of whole-brain functional networks. Compared to novices,
      BEs exhibited decreased and increased gray matter volume (GMV) in the amygdala
      and nucleus accumbens (NA), respectively. We also found increased FC between the
      amygdala and medial orbitofrontal cortex (mOFC) and decreased FC between the NA
      and medial prefrontal cortex (mPFC). Further GTA revealed differences in measures
      of the integration of the network and in the regional nodal characteristics of
      various brain regions activated during Baduk. This study provides evidence for
      structural and functional differences as well as altered topological organization
      of the whole-brain functional networks in BEs. Our findings also offer novel
      suggestions about the cognitive mechanisms behind Baduk expertise, which involves
      intuitive decision-making mediated by somatic marker circuitry and visuospatial
      processing. 

PMID- 24106472
TI  - What about the "Self" is Processed in the Posterior Cingulate Cortex?
AB  - In the past decade, neuroimaging research has begun to identify key brain regions
      involved in self-referential processing, most consistently midline structures
      such as the posterior cingulate cortex (PCC). The majority of studies have
      employed cognitive tasks such as judgment about trait adjectives or mind
      wandering, that have been associated with increased PCC activity. Conversely,
      tasks that share an element of present-centered attention (being "on task"),
      ranging from working memory to meditation, have been associated with decreased
      PCC activity. Given the complexity of cognitive processes that likely contribute
      to these tasks, the specific contribution of the PCC to self-related processes
      still remains unknown. Building on this prior literature, recent studies have
      employed sampling methods that more precisely link subjective experience to brain
      activity, such as real-time fMRI neurofeedback. This recent work suggests that
      PCC activity may represent a sub-component cognitive process of self-reference -
      "getting caught up in" one's experience. For example, getting caught up in a drug
      craving or a particular viewpoint. In this paper, we will review evidence across
      a number of different domains of cognitive neuroscience that converges in
      activation and deactivation of the PCC including recent neurophenomenological
      studies of PCC activity using real-time fMRI neurofeedback. 

PMID- 24106473
TI  - Synaptic polarity of the interneuron circuit controlling C. elegans locomotion.
AB  - Caenorhabditis elegans is the only animal for which a detailed neural
      connectivity diagram has been constructed. However, synaptic polarities in this
      diagram, and thus, circuit functions are largely unknown. Here, we deciphered the
      likely polarities of seven pre-motor neurons implicated in the control of worm's
      locomotion, using a combination of experimental and computational tools. We
      performed single and multiple laser ablations in the locomotor interneuron
      circuit and recorded times the worms spent in forward and backward locomotion. We
      constructed a theoretical model of the locomotor circuit and searched its all
      possible synaptic polarity combinations and sensory input patterns in order to
      find the best match to the timing data. The optimal solution is when either all
      or most of the interneurons are inhibitory and forward interneurons receive the
      strongest input, which suggests that inhibition governs the dynamics of the
      locomotor interneuron circuit. From the five pre-motor interneurons, only AVB and
      AVD are equally likely to be excitatory, i.e., they have probably similar number
      of inhibitory and excitatory connections to distant targets. The method used here
      has a general character and thus can be also applied to other neural systems
      consisting of small functional networks. 

PMID- 24106474
TI  - A large-scale neural network model of the influence of neuromodulatory levels on
      working memory and behavior.
AB  - The dorsolateral prefrontal cortex (dlPFC), which is regarded as the primary site
      for visuospatial working memory in the brain, is significantly modulated by
      dopamine (DA) and norepinephrine (NE). DA and NE originate in the ventral
      tegmental area (VTA) and locus coeruleus (LC), respectively, and have been shown
      to have an "inverted-U" dose-response profile in dlPFC, where the level of
      arousal and decision-making performance is a function of DA and NE
      concentrations. Moreover, there appears to be a sweet spot, in terms of the level
      of DA and NE activation, which allows for optimal working memory and behavioral
      performance. When either DA or NE is too high, input to the PFC is essentially
      blocked. When either DA or NE is too low, PFC network dynamics become noisy and
      activity levels diminish. Mechanisms for how this is occurring have been
      suggested, however, they have not been tested in a large-scale model with
      neurobiologically plausible network dynamics. Also, DA and NE levels have not
      been simultaneously manipulated experimentally, which is not realistic in vivo
      due to strong bi-directional connections between the VTA and LC. To address these
      issues, we built a spiking neural network model that includes D1, alpha2A, and
      alpha1 receptors. The model was able to match the inverted-U profiles that have
      been shown experimentally for differing levels of DA and NE. Furthermore, we were
      able to make predictions about what working memory and behavioral deficits may
      occur during simultaneous manipulation of DA and NE outside of their optimal
      levels. Specifically, when DA levels were low and NE levels were high, cues could
      not be held in working memory due to increased noise. On the other hand, when DA
      levels were high and NE levels were low, incorrect decisions were made due to
      weak overall network activity. We also show that lateral inhibition in working
      memory may play a more important role in increasing signal-to-noise ratio than
      increasing recurrent excitatory input. 

PMID- 24106475
TI  - A novel CPU/GPU simulation environment for large-scale biologically realistic
      neural modeling.
AB  - Computational Neuroscience is an emerging field that provides unique
      opportunities to study complex brain structures through realistic neural
      simulations. However, as biological details are added to models, the execution
      time for the simulation becomes longer. Graphics Processing Units (GPUs) are now
      being utilized to accelerate simulations due to their ability to perform
      computations in parallel. As such, they have shown significant improvement in
      execution time compared to Central Processing Units (CPUs). Most neural
      simulators utilize either multiple CPUs or a single GPU for better performance,
      but still show limitations in execution time when biological details are not
      sacrificed. Therefore, we present a novel CPU/GPU simulation environment for
      large-scale biological networks, the NeoCortical Simulator version 6 (NCS6). NCS6
      is a free, open-source, parallelizable, and scalable simulator, designed to run
      on clusters of multiple machines, potentially with high performance computing
      devices in each of them. It has built-in leaky-integrate-and-fire (LIF) and
      Izhikevich (IZH) neuron models, but users also have the capability to design
      their own plug-in interface for different neuron types as desired. NCS6 is
      currently able to simulate one million cells and 100 million synapses in quasi
      real time by distributing data across eight machines with each having two video
      cards. 

PMID- 24106476
TI  - Brain-derived neurotrophic factor in VMH as the causal factor for and therapeutic
      tool to treat visceral adiposity and hyperleptinemia in type 2 diabetic Goto
      Kakizaki rats.
AB  - We previously reported that the type 2 diabetic Goto-Kakizaki (GK) rats at young
      adult ages (6-12 weeks) exhibited increased visceral fat mass and
      hyperleptinemia, due to hyperphagia caused primarily by neuropeptide Y (NPY)
      overexpression in the hypothalamic arcuate nucleus. Later, we found that GK rats
      continued to exhibit mesenteric fat accumulation and hyperleptinemia at least
      until 26 weeks of age, while hyperphagia and NPY overexpression ceased at 15
      weeks of age. Therefore, we hypothesized that the long-lasting fat accumulation
      and hyperleptinemia are due to unidentified brain dysfunction other than NPY
      overexpression. In GK rats aged 26 weeks, glucose transporter-2 (GLUT2) mRNA
      expression in ventromedial hypothalamus (VMH) was markedly reduced in parallel
      with significant decreases in brain-derived neurotrophic factor (BDNF) mRNA level
      and BDNF-expressing cell numbers in the VMH. Pharmacologic inhibition of glucose
      utilization reduced BDNF mRNA expression in VMH in vivo and in vitro. The results
      suggested that impaired glucose utilization caused the reduction of BDNF. On the
      other hand, intracerebroventricular injection of BDNF for 6 days ameliorated
      hyperleptinemia in a long-lasting manner concurrently with feeding suppression in
      GK rats. Restricted feeding paired to BDNF-treated rats reduced plasma leptin
      level only transiently. BDNF treatment also reduced mesenteric fat mass in GK
      rats. These results reveal a novel action mode of BDNF to long-lastingly
      counteract visceral adiposity and hyperleptinemia in addition to and
      independently of its anorexigenic action. These results suggest that visceral fat
      accumulation and hyperleptinemia are at least partly due to the reduction of BDNF
      in VMH primarily caused by impaired glucose utilization in GK rats. The BDNF
      supplementation could provide an effective treatment of visceral obesity,
      hyperleptinemia and leptin resistance in type 2 diabetes. 

PMID- 24106477
TI  - Co-morbidity of depression and anxiety in common age-related eye diseases: a
      population-based study of 662 adults.
AB  - This study examined the prevalence of co-morbid age-related eye disease and
      symptoms of depression and anxiety in late life, and the relative roles of visual
      function and disease in explaining symptoms of depression and anxiety. A
      community-based sample of 662 individuals aged over 70 years was recruited
      through the electoral roll. Vision was measured using a battery of tests
      including high and low contrast visual acuity, contrast sensitivity, motion
      sensitivity, stereoacuity, Useful Field of View, and visual fields. Depression
      and anxiety symptoms were measured using the Goldberg scales. The prevalence of
      self-reported eye disease [cataract, glaucoma, or age-related macular
      degeneration (AMD)] in the sample was 43.4%, with 7.7% reporting more than one
      form of ocular pathology. Of those with no eye disease, 3.7% had clinically
      significant depressive symptoms. This rate was 6.7% among cataract patients, 4.3%
      among those with glaucoma, and 10.5% for AMD. Generalized linear models adjusting
      for demographics, general health, treatment, and disability examined self
      reported eye disease and visual function as correlates of depression and anxiety.
      Depressive symptoms were associated with cataract only, AMD, comorbid eye
      diseases and reduced low contrast visual acuity. Anxiety was significantly
      associated with self-reported cataract, and reduced low contrast visual acuity,
      motion sensitivity and contrast sensitivity. We found no evidence for elevated
      rates of depressive or anxiety symptoms associated with self-reported glaucoma.
      The results support previous findings of high rates of depression and anxiety in
      cataract and AMD, and in addition show that mood and anxiety are associated with
      objective measures of visual function independently of self-reported eye disease.
      The findings have implications for the assessment and treatment of mental health
      in the context of late-life visual impairment. 

PMID- 24106478
TI  - Integrative EEG biomarkers predict progression to Alzheimer's disease at the MCI
      stage.
AB  - Alzheimer's disease (AD) is a devastating disorder of increasing prevalence in
      modern society. Mild cognitive impairment (MCI) is considered a transitional
      stage between normal aging and AD; however, not all subjects with MCI progress to
      AD. Prediction of conversion to AD at an early stage would enable an earlier, and
      potentially more effective, treatment of AD. Electroencephalography (EEG)
      biomarkers would provide a non-invasive and relatively cheap screening tool to
      predict conversion to AD; however, traditional EEG biomarkers have not been
      considered accurate enough to be useful in clinical practice. Here, we aim to
      combine the information from multiple EEG biomarkers into a diagnostic
      classification index in order to improve the accuracy of predicting conversion
      from MCI to AD within a 2-year period. We followed 86 patients initially
      diagnosed with MCI for 2 years during which 25 patients converted to AD. We show
      that multiple EEG biomarkers mainly related to activity in the beta-frequency
      range (13-30 Hz) can predict conversion from MCI to AD. Importantly, by
      integrating six EEG biomarkers into a diagnostic index using logistic regression
      the prediction improved compared with the classification using the individual
      biomarkers, with a sensitivity of 88% and specificity of 82%, compared with a
      sensitivity of 64% and specificity of 62% of the best individual biomarker in
      this index. In order to identify this diagnostic index we developed a data mining
      approach implemented in the Neurophysiological Biomarker Toolbox
      (http://www.nbtwiki.net/). We suggest that this approach can be used to identify
      optimal combinations of biomarkers (integrative biomarkers) also in other
      modalities. Potentially, these integrative biomarkers could be more sensitive to
      disease progression and response to therapeutic intervention. 

PMID- 24106479
TI  - Adrenergic receptors and metabolism: role in development of cardiovascular
      disease.
AB  - Activation of the adrenergic system has a profound effects on metabolism.
      Increased circulating catecholamine and activation of the different adrenergic
      receptors deployed in the various organs produce important metabolic responses
      which include: (1) increased lipolysis and elevated levels of fatty acids in
      plasma, (2) increased gluconeogenesis by the liver to provide substrate for the
      brain, and (3) moderate inhibition of insulin release by the pancreas to conserve
      glucose and to shift fuel metabolism of muscle in the direction of fatty acid
      oxidation. These physiological responses, typical of the stress conditions, are
      demonstrated to be detrimental for the functioning of different organs like the
      cardiac muscle when they become chronic. Indeed, a common feature of many
      pathological conditions involving over-activation of the adrenergic system is the
      development of metabolic alterations which can include insulin resistance,
      altered glucose and lipid metabolism and mitochondrial dysfunction. These
      patterns are involved with a variably extent among the different pathologies,
      however, they are in general strictly correlated to the level of activation of
      the adrenergic system. Here we will review the effects of the different
      adrenergic receptors subtypes on the metabolic variation observed in important
      disease like Heart Failure. 

PMID- 24106482
TI  - DSM-5 Trauma and Stress-Related Disorders: Implications for Screening for Cancer
      Related Stress.

PMID- 24106480
TI  - Calcium-permeable ion channels in control of autophagy and cancer.
AB  - Autophagy, or cellular self-eating, is a tightly regulated cellular pathway the
      main purpose of which is lysosomal degradation and subsequent recycling of
      cytoplasmic material to maintain normal cellular homeostasis. Defects in
      autophagy are linked to a variety of pathological states, including cancer.
      Cancer is the disease associated with abnormal tissue growth following an
      alteration in such fundamental cellular processes as apoptosis, proliferation,
      differentiation, migration and autophagy. The role of autophagy in cancer is
      complex, as it can promote both tumor prevention and survival/treatment
      resistance. It's now clear that modulation of autophagy has a great potential in
      cancer diagnosis and treatment. Recent findings identified intracellular calcium
      as an important regulator of both basal and induced autophagy. Calcium is a
      ubiquitous secondary messenger which regulates plethora of physiological and
      pathological processes such as aging, neurodegeneration and cancer. The role of
      calcium and calcium-permeable channels in cancer is well-established, whereas the
      information about molecular nature of channels regulating autophagy and the
      mechanisms of this regulation is still limited. Here we review existing
      mechanisms of autophagy regulation by calcium and calcium-permeable ion channels.
      Furthermore, we will also discuss some calcium-permeable channels as the
      potential new candidates for autophagy regulation. Finally we will propose the
      possible link between calcium permeable channels, autophagy and cancer
      progression and therapeutic response. 

PMID- 24106483
TI  - Word frequency cues word order in adults: cross-linguistic evidence.
AB  - One universal feature of human languages is the division between grammatical
      functors and content words. From a learnability point of view, functors might
      provide entry points or anchors into the syntactic structure of utterances due to
      their high frequency. Despite its potentially universal scope, this hypothesis
      has not yet been tested on typologically different languages and on populations
      of different ages. Here we report a corpus study and an artificial grammar
      learning experiment testing the anchoring hypothesis in Basque, Japanese, French,
      and Italian adults. We show that adults are sensitive to the distribution of
      functors in their native language and use them when learning new linguistic
      material. However, compared to infants' performance on a similar task, adults
      exhibit a slightly different behavior, matching the frequency distributions of
      their native language more closely than infants do. This finding bears on the
      issue of the continuity of language learning mechanisms. 

PMID- 24106484
TI  - Multinomial tree models for assessing the status of the reference in studies of
      the accuracy of tools for binary classification.
AB  - Studies that evaluate the accuracy of binary classification tools are needed.
      Such studies provide 2 * 2 cross-classifications of test outcomes and the
      categories according to an unquestionable reference (or gold standard). However,
      sometimes a suboptimal reliability reference is employed. Several methods have
      been proposed to deal with studies where the observations are cross-classified
      with an imperfect reference. These methods require that the status of the
      reference, as a gold standard or as an imperfect reference, is known. In this
      paper a procedure for determining whether it is appropriate to maintain the
      assumption that the reference is a gold standard or an imperfect reference, is
      proposed. This procedure fits two nested multinomial tree models, and assesses
      and compares their absolute and incremental fit. Its implementation requires the
      availability of the results of several independent studies. These should be
      carried out using similar designs to provide frequencies of cross-classification
      between a test and the reference under investigation. The procedure is applied in
      two examples with real data. 

PMID- 24106485
TI  - Developmental changes in visual short-term memory in infancy: evidence from eye
      tracking.
AB  - We assessed visual short-term memory (VSTM) for color in 6- and 8-month-old
      infants (n = 76) using a one-shot change detection task. In this task, a sample
      array of two colored squares was visible for 517 ms, followed by a 317-ms
      retention period and then a 3000-ms test array consisting of one unchanged item
      and one item in a new color. We tracked gaze at 60 Hz while infants looked at the
      changed and unchanged items during test. When the two sample items were different
      colors (Experiment 1), 8-month-old infants exhibited a preference for the changed
      item, indicating memory for the colors, but 6-month-olds exhibited no evidence of
      memory. When the two sample items were the same color and did not need to be
      encoded as separate objects (Experiment 2), 6-month-old infants demonstrated
      memory. These results show that infants can encode information in VSTM in a
      single, brief exposure that simulates the timing of a single fixation period in
      natural scene viewing, and they reveal rapid developmental changes between 6 and
      8 months in the ability to store individuated items in VSTM. 

PMID- 24106486
TI  - Great apes can defer exchange: a replication with different results suggesting
      future oriented behavior.
AB  - The topic of cognitive foresight in non-human animals has received considerable
      attention in the last decade. The main questions concern whether the animals can
      prepare for upcoming situations which are, to various degrees, contextually or
      sensorially detached from the situation in which the preparations are made.
      Studies on great apes have focused on tool-related tasks, e.g., the ability to
      select a tool which is functional only in the future. Dufour and Sterck (2008),
      however, investigated whether chimpanzees were also able to prepare for a future
      exchange with a human: an object exchanged for a food item. The study included
      extensive training on the exchangeable item, which is traditionally not
      compatible with methods for studying planning abilities, as associative learning
      cannot be precluded. Nevertheless, despite this training, the chimpanzees could
      not solve the deferred exchange task. Given that great apes can plan for tool
      use, these results are puzzling. In addition, claims that great ape foresight is
      highly limited has been based on this study (Suddendorf and Corballis, 2010).
      Here we partly replicated Dufour and Sterck's study to discern whether temporally
      deferred and spatially displaced exchange tasks are beyond the capabilities of
      great apes. In addition to chimpanzees we tested orangutans. One condition
      followed the one used by Dufour and Sterck, in which the exchange items,
      functional only in the future, are placed at a location that freely allows for
      selections by the subjects. In order to test the possibility that the choice set
      up could explain the negative results in Dufour and Sterck's study, our second
      condition followed a method used in the planning study by Osvath and Osvath
      (2008), where the subjects make a forced one-item-choice from a tray. We found
      that it is within the capabilities of chimpanzees and orangutans to perform
      deferred exchange in both conditions. 

PMID- 24106481
TI  - Adipose tissue immunity and cancer.
AB  - Inflammation and altered immune response are important components of obesity and
      contribute greatly to the promotion of obesity-related metabolic complications,
      especially cancer development. Adipose tissue expansion is associated with
      increased infiltration of various types of immune cells from both the innate and
      adaptive immune systems. Thus, adipocytes and infiltrating immune cells secrete
      pro-inflammatory adipokines and cytokines providing a microenvironment favorable
      for tumor growth. Accumulation of B and T cells in adipose tissue precedes
      macrophage infiltration causing a chronic low-grade inflammation. Phenotypic
      switching toward M1 macrophages and Th1 T cells constitutes an important
      mechanism described in the obese state correlating with increased tumor growth
      risk. Other possible synergic mechanisms causing a dysfunctional adipose tissue
      include fatty acid-induced inflammation, oxidative stress, endoplasmic reticulum
      stress, and hypoxia. Recent investigations have started to unravel the intricacy
      of the cross-talk between tumor cell/immune cell/adipocyte. In this sense, future
      therapies should take into account the combination of anti-inflammatory
      approaches that target the tumor microenvironment with more sophisticated and
      selective anti-tumoral drugs. 

PMID- 24106487
TI  - The Burden and Impact of Vertigo: Findings from the REVERT Patient Registry.
AB  - OBJECTIVE: Despite the high prevalence of vertigo globally and an acknowledged,
      but under-reported, effect on an individual's wellbeing, few studies have
      evaluated the burden on healthcare systems and society. This study was aimed to
      quantitatively determine the impact of vertigo on healthcare resource use and
      work productivity. METHODS: The economic burden of vertigo was assessed through a
      multi-country, non-interventional, observational registry of vertigo patients:
      the Registry to Evaluate the Burden of Disease in Vertigo. Patients included were
      those with a new diagnosis of Meniere's disease, benign paroxysmal positional
      vertigo, other vertigo of peripheral vestibular origin, or peripheral vestibular
      vertigo of unknown origin. RESULTS: A total of 4,294 patients at 618 centers in
      13 countries were included during the registry. Of the 4,105 patients analyzed,
      only half were in employment. Among this working patient population, 69.8% had
      reduced their workload, 63.3% had lost working days, and 4.6% had changed and
      5.7% had quit their jobs, due to vertigo symptoms. Use of healthcare services
      among patients was high. In the 3 months preceding Visit 1, patients used
      emergency services 0.4 +/- 0.9 times, primary care consultations 1.6 +/- 1.8
      times, and specialist consultations 1.4 +/- 2.0 times (all mean +/- SD). A mean
      of 2.0 +/- 5.4 days/patient was also spent in hospital due to vertigo.
      CONCLUSION: In addition to the negative impact on the patient from a humanistic
      perspective, vertigo has considerable impact on work productivity and healthcare
      resource use.

PMID- 24106488
TI  - Exocytosis and endocytosis in neuroendocrine cells: inseparable membranes!
AB  - Although much has been learned concerning the mechanisms of secretory vesicle
      formation and fusion at donor and acceptor membrane compartments, relatively
      little attention has been paid toward understanding how cells maintain a
      homeostatic membrane balance through vesicular trafficking. In neurons and
      neuroendocrine cells, release of neurotransmitters, neuropeptides, and hormones
      occurs through calcium-regulated exocytosis at the plasma membrane. To allow
      recycling of secretory vesicle components and to preserve organelles integrity,
      cells must initiate and regulate compensatory membrane uptake. This review
      relates the fate of secretory granule membranes after full fusion exocytosis in
      neuroendocrine cells. In particular, we focus on the potential role of lipids in
      preserving and sorting secretory granule membranes after exocytosis and we
      discuss the potential mechanisms of membrane retrieval. 

PMID- 24106489
TI  - Protein Kinase C Phosphorylates the System N Glutamine Transporter SN1 (Slc38a3)
      and Regulates Its Membrane Trafficking and Degradation.
AB  - The system N transporter SN1 (also known as SNAT3) is enriched on perisynaptic
      astroglial cell membranes. SN1 mediates electroneutral and bidirectional
      glutamine transport, and regulates the intracellular as well as the extracellular
      concentrations of glutamine. We hypothesize that SN1 participates in the
      glutamate/gamma-aminobutyric acid (GABA)-glutamine cycle and regulates the amount
      of glutamine supplied to the neurons for replenishment of the neurotransmitter
      pools of glutamate and GABA. We also hypothesize that its activity on the plasma
      membrane is regulated by protein kinase C (PKC)-mediated phosphorylation and that
      SN1 activity has an impact on synaptic plasticity. This review discusses reports
      on the regulation of SN1 by PKC and presents a consolidated model for regulation
      and degradation of SN1 and the subsequent functional implications. As SN1
      function is likely also regulated by PKC-mediated phosphorylation in peripheral
      organs, the same mechanisms may, thus, have impact on e.g., pH regulation in the
      kidney, urea formation in the liver, and insulin secretion in the pancreas. 

PMID- 24106490
TI  - Bacillus cereus cell response upon exposure to acid environment: toward the
      identification of potential biomarkers.
AB  - Microorganisms are able to adapt to different environments and evolve rapidly,
      allowing them to cope with their new environments. Such adaptive response and
      associated protections toward other lethal stresses, is a crucial survival
      strategy for a wide spectrum of microorganisms, including food spoilage bacteria,
      pathogens, and organisms used in functional food applications. The growing demand
      for minimal processed food yields to an increasing use of combination of hurdles
      or mild preservation factors in the food industry. A commonly used hurdle is low
      pH which allows the decrease in bacterial growth rate but also the inactivation
      of pathogens or spoilage microorganisms. Bacillus cereus is a well-known food
      borne pathogen leading to economical and safety issues in food industry. Because
      survival mechanisms implemented will allow bacteria to cope with environmental
      changes, it is important to provide understanding of B. cereus stress response.
      Thus this review deals with the adaptive traits of B. cereus cells facing to acid
      stress conditions. The acid stress response of B. cereus could be divided into
      four groups (i) general stress response (ii) pH homeostasis, (iii) metabolic
      modifications and alkali production and (iv) secondary oxidative stress response.
      This current knowledge may be useful to understand how B. cereus cells may cope
      to acid environment such as encountered in food products and thus to find some
      molecular biomarkers of the bacterial behavior. These biomarkers could be
      furthermore used to develop new microbial behavior prediction tools which can
      provide insights into underlying molecular physiological states which govern the
      behavior of microorganisms and thus opening the avenue toward the detection of
      stress adaptive behavior at an early stage and the control of stress-induced
      resistance throughout the food chain. 

PMID- 24106491
TI  - IFNalpha Inducible Models of Murine SLE.
AB  - The role of type I interferons (IFNs) in SLE pathogenesis has been a subject of
      intense investigation in the last decade. The strong link between type I IFNs and
      SLE was initially provided by ex vivo studies showing that exposure of peripheral
      blood mononuclear cells to immune complexes from SLE patients elicits a signature
      of IFN inducible genes and was then further highlighted by human genetic studies.
      The mechanisms by which type I IFNs, especially IFN alpha (IFNalpha), modulate
      the immune system and exacerbate SLE have been largely elucidated through studies
      in mouse lupus models. In this review, we discuss the characteristics of several
      such models in which disease is accelerated by ectopically expressed IFNalpha. We
      also summarize several studies which tested therapeutic interventions in these
      models and discuss the advantages and disadvantages of using IFNalpha accelerated
      models to study experimental treatments for lupus. 

PMID- 24106492
TI  - Angiosperm-like pollen and Afropollis from the Middle Triassic (Anisian) of the
      Germanic Basin (Northern Switzerland).
AB  - Here we report on angiosperm-like pollen and Afropollis from the Anisian (Middle
      Triassic, 247.2-242.0 Ma) of a mid-latitudinal site in Northern Switzerland.
      Small monosulcate pollen grains with typical reticulate (semitectate) sculpture,
      columellate structure of the sexine and thin nexine show close similarities to
      early angiosperm pollen known from the Early Cretaceous. However, they differ in
      their extremely thin inner layer (nexine). Six different pollen types (I-VI) are
      differentiated based on size, reticulation pattern, and exine structure. The
      described pollen grains show all the essential features of angiosperm pollen.
      However, considering the lack of a continuous record throughout the lower part of
      the Mesozoic and the comparison with the oldest Cretaceous finds we suggest an
      affinity to an angiosperm stem group. Together with the previously published
      records from the Middle Triassic of the Barents Sea area the angiosperm-like
      pollen grains reflect a considerable diversity of the parent plants during the
      Middle Triassic. Sedimentological evidence and associated palynofloras also
      suggest a remarkable ecological range for these plants. Associated with these
      grains we found pollen comparable to the genus Afropollis. Representatives of
      this genus are commonly recorded in Lower Cretaceous sediments of low latitudes,
      but until now had no record from the lower part of the Mesozoic. 

PMID- 24106494
TI  - Toward new perspectives on the interaction of iron and sulfur metabolism in
      plants.
AB  - The deficiency of nutrients has been extensively investigated because of its
      impact on plant growth and yield. So far, the effects of a combined nutrient
      limitation have rarely been analyzed, although such situations are likely to
      occur in agroecosystems. Iron (Fe) is a prerequisite for many essential cellular
      functions. Its availability is easily becoming limiting for plant growth and thus
      higher plants have evolved different strategies to cope with Fe deficiency.
      Sulfur (S) is an essential macro-nutrient and the responses triggered by shortage
      situations have been well characterized. The interaction between these two
      nutrients is less investigated but might be of particular importance because most
      of the metabolically active Fe is bound to S in Fe-S clusters. The biosynthesis
      of Fe-S clusters requires the provision of reduced S and chelated Fe in a defined
      stoichiometric ratio, strongly suggesting coordination between the metabolisms of
      the two nutrients. Here the available information on interactions between Fe and
      S nutritional status is evaluated. Experiments with Arabidopsis thaliana and crop
      plants indicate a co-regulation and point to a possible role of Fe-S cluster
      synthesis or abundance in the Fe/S network. 

PMID- 24106495
TI  - In search of solutions to grapevine trunk diseases through "crowd-sourced"
      science.

PMID- 24106496
TI  - Research on hotspot discovery in internet public opinions based on improved K
      means.
AB  - How to discover hotspot in the Internet public opinions effectively is a hot
      research field for the researchers related which plays a key role for governments
      and corporations to find useful information from mass data in the Internet. An
      improved K-means algorithm for hotspot discovery in internet public opinions is
      presented based on the analysis of existing defects and calculation principle of
      original K-means algorithm. First, some new methods are designed to preprocess
      website texts, select and express the characteristics of website texts, and
      define the similarity between two website texts, respectively. Second, clustering
      principle and the method of initial classification centers selection are analyzed
      and improved in order to overcome the limitations of original K-means algorithm.
      Finally, the experimental results verify that the improved algorithm can improve
      the clustering stability and classification accuracy of hotspot discovery in
      internet public opinions when used in practice. 

PMID- 24106497
TI  - Tamarind Seed Xyloglucans Promote Proliferation and Migration of Human Skin Cells
      through Internalization via Stimulation of Proproliferative Signal Transduction
      Pathways.
AB  - Xyloglucans (XGs) of Tamarindus indica L. Fabaceae are used as drug vehicles or
      as ingredients of cosmetics. Two xyloglucans were extracted from T. indica seed
      with cold water (TSw) and copper complex precipitation (TSc). Both were analyzed
      in regard to composition and influence on cell viability, proliferation, cell
      cycle progression, migration, MAPK phosphorylation, and gene expression of human
      skin keratinocytes (NHEK and HaCaT) and fibroblasts (NHDF) in vitro. TSw and TSc
      differed in molecular weight, rhamnose content, and ratios of xylose, arabinose,
      galactose, and glucose. Both XGs improved keratinocytes and fibroblast
      proliferation, promoted the cell cycle, and stimulated migration and
      intracellular enzyme activity of NHDF after endosomal uptake. Only TSw
      significantly enhanced HaCaT migration and extracellular enzyme activity of NHDF
      and HaCaT. TSw and TSc predominantly enhanced the phosphorylation of molecules
      that referred to Erk signaling in NHEK. In NHDF parts of the integrin signaling
      and SAPK/JNK pathway were affected. Independent of cell type TSw marginally
      regulated the expression of genes, which referred to membrane proteins,
      cytoskeleton, cytokine signaling, and ECM as well as to processes of metabolism
      and transcription. Results show that T. indica xyloglucans promote skin
      regeneration by a direct influence on cell proliferation and migration. 

PMID- 24106493
TI  - Root apex transition zone as oscillatory zone.
AB  - Root apex of higher plants shows very high sensitivity to environmental stimuli.
      The root cap acts as the most prominent plant sensory organ; sensing diverse
      physical parameters such as gravity, light, humidity, oxygen, and critical
      inorganic nutrients. However, the motoric responses to these stimuli are
      accomplished in the elongation region. This spatial discrepancy was solved when
      we have discovered and characterized the transition zone which is interpolated
      between the apical meristem and the subapical elongation zone. Cells of this zone
      are very active in the cytoskeletal rearrangements, endocytosis and endocytic
      vesicle recycling, as well as in electric activities. Here we discuss the
      oscillatory nature of the transition zone which, together with several other
      features of this zone, suggest that it acts as some kind of command center. In
      accordance with the early proposal of Charles and Francis Darwin, cells of this
      root zone receive sensory information from the root cap and instruct the motoric
      responses of cells in the elongation zone. 

PMID- 24106498
TI  - Gastroesophageal Reflux Disease Relief in Patients Treated with Rabeprazole 20 mg
      versus Omeprazole 20 mg: A Meta-Analysis.
AB  - Background. Randomized controlled trials (RCTs) have been conducted comparing the
      efficacy of rabeprazole 20 mg or omeprazole 20 mg once daily for patients with
      erosive gastroesophageal reflux disease (GERD). Until now, no study has
      synthesized all available data examining this issue. Method. Medline, Embase, and
      the Cochrane central register of controlled trials were searched (through
      December 2012). Eligible RCTs recruited adults with erosive GERD and reported
      endoscopic and symptomatic relief rates at the last point of follow-up. The
      effect of rabeprazole versus omeprazole was reported as relative risk (RR) of
      relief with a 95% confidence interval (CI). Results. The search identified 605
      citations, and six RCTs containing 1,895 patients were eligible. Endoscopic
      relief rates were not significantly different between rabeprazole 20 mg and
      omeprazole 20 mg in treatment trials of up to 8 weeks. Heartburn relief rates
      were significantly different between the two groups for 8-week treatment trials.
      Adverse events were not significantly different between the two groups for 8-week
      treatment trials. Conclusion. These data suggest that rabeprazole demonstrates a
      clinical advantage over omeprazole in symptomatic relief but no significant
      difference in endoscopic relief of erosive GERD for up to 8 weeks of treatment.
      Rabeprazole and omeprazole were both tolerated by GERD patients. 

PMID- 24106500
TI  - Retracted: A prospective study of early loaded single implant-retained mandibular
      overdentures: Preliminary one-year results.

PMID- 24106501
TI  - Retracted: Free Radical Production in Immune Cell Systems Induced by Ti, Ti6Al4V
      and SS Assessed by Chemiluminescence Probe Pholasin Assay.

PMID- 24106502
TI  - Anti-CCP Antibodies Are Not Associated with Familial Mediterranean Fever in
      Childhood.
AB  - Objective. Anticyclic citrullinated peptide antibodies (anti-CCP) testing is
      useful in the diagnosis of rheumatoid arthritis (RA) with high specificity.
      Arthritis is a very common clinical manifestation in children with familial
      Mediterranean fever (FMF). The aim of the study was to show the presence of anti
      CCP antibodies in child individuals diagnosed with FMF. Material and Methods. The
      study groups comprised one hundred and twenty-six patients (126) diagnosed with
      FMF (female/male (n): 66/60) and 50 healthy controls (female/male (n): 25/25).
      Clinical and laboratory assessments of the FMF patients were performed during
      attack-free periods. Erythrocyte sedimentation rate (ESR), serum C-reactive
      protein (CRP), fibrinogen, and anti-CCP antibody levels were measured. Results.
      Anti-CCP was negative in healthy controls and also in all FMF patients. There was
      not a significant difference in anti-CCP between the patient and the control
      groups. Our study has shown that anti-CCP was correlated moderately with age (rs
      = 0.271; P = 0.0020), duration of illness (rs = 0.331; P < 0.0001), and
      colchicine therapy (rs = 0.259; P = 0.004). Conclusion. Our data show that anti
      CCP antibodies are not associated with FMF. Anti-CCP does not have a priority for
      identifying FMF arthritis from the other inflammatory arthritis. 

PMID- 24106503
TI  - Isolated spherophakia and glaucoma.
AB  - We report a case of spherophakia that caused glaucoma and describe the
      characteristics and the ultrasound biomicroscopy findings as well as the
      mechanism and management of glaucoma in spherophakia. We suggest considering lens
      extraction to manage glaucoma in spherophakia and discuss the surgical
      considerations and possible complications of such an intervention. 

PMID- 24106504
TI  - A Case Report of Iatrogenic Pulmonary Artery Injury due to Chest-Tube Insertion
      Repaired under Cardiopulmonary Bypass.
AB  - The authors presented a case of a 50-year-old patient with multiple trauma who
      suffered from the inadvertent cannulation of the main pulmonary artery at the
      second attempt of left chest drainage. Pulmonary artery injury has been suspected
      because early chest tube production was 2300 mL of blood. CT scan showed injury
      of the trunk of the pulmonary artery, left hemothorax, and suspect damage of the
      right branch of the pulmonary artery. That chest tube touched the posterior wall
      of ascending aorta. Surgical approach was median sternotomy. Exploration showed a
      perforation of the trunk of pulmonary artery without lesion of the right
      pulmonary branch and the posterior wall of the ascending aorta. The lesion was
      repaired under normothermic partial cardiopulmonary bypass. Postoperative period
      was free of events. Review of the literatures for this rare case report has been
      done. 

PMID- 24106499
TI  - The role of "mixed" orexigenic and anorexigenic signals and autoantibodies
      reacting with appetite-regulating neuropeptides and peptides of the adipose
      tissue-gut-brain axis: relevance to food intake and nutritional status in
      patients with anorexia nervosa and bulimia nervosa.
AB  - Eating disorders such as anorexia (AN) and bulimia nervosa (BN) are characterized
      by abnormal eating behavior. The essential aspect of AN is that the individual
      refuses to maintain a minimal normal body weight. The main features of BN are
      binge eating and inappropriate compensatory methods to prevent weight gain. The
      gut-brain-adipose tissue (AT) peptides and neutralizing autoantibodies play an
      important role in the regulation of eating behavior and growth hormone release.
      The mechanisms for controlling food intake involve an interplay between gut,
      brain, and AT. Parasympathetic, sympathetic, and serotoninergic systems are
      required for communication between brain satiety centre, gut, and AT. These
      neuronal circuits include neuropeptides ghrelin, neuropeptide Y (NPY), peptide YY
      (PYY), cholecystokinin (CCK), leptin, putative anorexigen obestatin, monoamines
      dopamine, norepinephrine (NE), serotonin, and neutralizing autoantibodies. This
      extensive and detailed report reviews data that demonstrate that hunger-satiety
      signals play an important role in the pathogenesis of eating disorders.
      Neuroendocrine dysregulations of the AT-gut-brain axis peptides and neutralizing
      autoantibodies may result in AN and BN. The circulating autoantibodies can be
      purified and used as pharmacological tools in AN and BN. Further research is
      required to investigate the orexigenic/anorexigenic synthetic analogs and
      monoclonal antibodies for potential treatment of eating disorders in clinical
      practice. 

PMID- 24106505
TI  - A late presentation of a fatal disease: juvenile hemochromatosis.
AB  - Juvenile hemochromatosis is a rare and severe form of hereditary hemochromatosis.
      We report the case of a 39-year-old female who presented with heart failure and
      cirrhosis from previously unrecognized juvenile hemochromatosis. This is the
      latest presentation described in the literature. An important clue to the
      diagnosis was a history of amenorrhea since the age of 20 that had never been
      investigated. The patient died of intractable heart failure two months after the
      initial presentation. Juvenile hemochromatosis should be suspected in a young
      patient with endocrine or cardiac manifestations. Early diagnosis is crucial
      since phlebotomy can improve the prognosis and delay or prevent progression to
      heart failure and cirrhosis. 

PMID- 24106506
TI  - Can serum tenascin-C be used as a marker of inflammation in patients with dilated
      cardiomyopathy?
AB  - Background. Tenascin-C (TN-C) is an extracellular matrix glycoprotein that
      appears at sites of inflammation in cardiac pathologies. Aim of the Work. To
      evaluate the role of TN-C as a marker for active inflammation in children with
      dilated cardiomyopathy (DCM). Subjects and Methods. 24 consecutive patients with
      primary nonfamilial DCM aged 6-72 months (mean 45.19 +/- 11.03) were divided into
      group I, twelve patients with acute onset DCM (<6 months duration), and group II,
      twelve patients with chronic DCM (>6 months duration), and compared to 20 healthy
      age- and sex-matched controls. Investigations included estimation of serum TN-C
      and echocardiographic evaluation using M-mode and 2D speckle tracking
      echocardiography (STE). Results. Serum TN-C showed a higher significant
      statistical elevation among patients than controls (P < 0.001) and in group I
      than group II (P < 0.001). EF was significantly decreased, and LVEDD and EDV
      increased in patients than controls and in GI than GII. STE showed a
      statistically significant difference in global peak strain longitudinal (GPSL)
      average in patients than controls (P < 0.05) and between GI and GII (P < 0.001).
      STE wall motion scoring showed normokinesia (33.5%), hypokinesia (8.33%), and
      akinesia (50%) in GI and hypokinesia (100%) in GII. There was a statistically
      significant positive correlation between serum TN-C and GPSL average.
      Conclusions. Increased serum TN-C can be used as a marker of inflammation in DCM
      and is associated with the severity of heart failure and LV dysfunction as
      detected by STE. 

PMID- 24106507
TI  - Development and application of neural stem cells for treating various human
      neurological diseases in animal models.
AB  - Stem cells derived from adult tissues or the inner cell mass (ICM) of embryos in
      the mammalian blastocyst (BL) stage are capable of self-renewal and have
      remarkable potential for undergoing lineage-specific differentiation under in
      vitro culturing conditions. In particular, neural stem cells (NSCs) that self
      renew and differentiate into major cell types of the brain exist in the
      developing and adult central nervous system (CNS). The exact function and
      distribution of NSCs has been assessed, and they represent an interesting
      population that includes astrocytes, oligodendrocytes, and neurons. Many
      researchers have demonstrated functional recovery in animal models of various
      neurological diseases such as stroke, Parkinson's disease (PD), brain tumors, and
      metastatic tumors. The safety and efficacy of stem cell-based therapies (SCTs)
      are also being evaluated in humans. The therapeutic efficacy of NSCs has been
      shown in the brain disorder-induced animal models, and animal models may be well
      established to perform the test before clinical stage. Taken together, data from
      the literature have indicated that therapeutic NSCs may be useful for selectively
      treating diverse types of human brain diseases without incurring adverse effects.

PMID- 24106508
TI  - Morphometrical dimensions of the sheep thoracolumbar vertebrae as seen on
      digitised CT images.
AB  - The sheep spine is widely used as a model for preclinical research in human
      medicine to test new spinal implants and surgical procedures. Therefore, precise
      morphometric data are needed. The present study aimed to provide computed
      tomographic (CT) morphometry of sheep thoracolumbar spine. Five adult normal
      Merino sheep were included in this study. Sheep were anaesthetised and positioned
      in sternal recumbency. Subsequently, transverse and sagittal images were obtained
      using a multi-detector-row helical CT scanner. Measurements of the vertebral
      bodies, pedicles, intervertebral disc and transverse processes were performed
      with dedicated software. Vertebral bodies and the spinal canal were wider than
      they were deep, most obviously in the lumbar vertebrae. The intervertebral discs
      were as much as 57.4% thicker in the lumbar than in the thoracic spine. The
      pedicles were higher and longer than they were wide over the entire thoracolumbar
      spine. In conclusion, the generated data can serve as a CT reference for the
      ovine thoracolumbar spine and may be helpful in using sheep spine as a model for
      human spinal research. 

PMID- 24106509
TI  - Systemic administration of low dosage of tetanus toxin decreases cell
      proliferation and neuroblast differentiation in the mouse hippocampal dentate
      gyrus.
AB  - IN THE PRESENT STUDY, WE INVESTIGATED THE EFFECT OF TETAUS TOXIN (TET) ON CELL
      PROLIFERATION AND NEUROBLAST DIFFERENTIATION USING SPECIFIC MARKERS: 5-bromo-2
      deoxyuridine (BrdU) as an exogenous marker for cell proliferation, Ki-67 as an
      endogenous marker for cell proliferation and doublecortin (DCX) as a marker for
      neuroblasts in the mouse hippocampal dentate gyrus (DG) after TeT treatment. Mice
      were intraperitoneally administered 2.5 and 10 ng/kg TeT and sacrificed 15 days
      after the treatment. In both the TeT-treated groups, no neuronal death occurred
      in any layers of the DG using neuronal nuclei (NeuN, a neuron nuclei maker) and
      Fluoro-Jade B (F-J B, a high-affinity fluorescent marker for the localization of
      neuronal degeneration). In addition, no significant change in glial activation in
      both the 2.5 and 10 ng/kg TeT-treated-groups was found by GFAP (a marker for
      astrocytes) and Iba-1 (a marker for microglia) immunohistochemistry. However, in
      the 2.5 ng/kg TeT-treated-group, the mean number of BrdU, Ki-67 and DCX
      immunoreactive cells, respectively, were apparently decreased compared to the
      control group, and the mean number of each in the 10 ng/kg TeT-treated-group was
      much more decreased. In addition, processes of DCX-immunoreactive cells, which
      projected into the molecular layer, were short compared to those in the control
      group. In brief, our present results show that low dosage (10 ng/kg) TeT
      treatment apparently decreased cell proliferation and neuroblast differentiation
      in the mouse hippocampal DG without distinct gliosis as well as any loss of adult
      neurons. 

PMID- 24106510
TI  - Focal cerebral ischemic injury decreases calbindin expression in brain tissue and
      HT22 cells.
AB  - Calbindin is a calcium binding protein that controls intracellular calcium levels
      and has a neuroprotective function against apoptotic stimuli. We investigated the
      expression of calbindin in ischemic brain injury. Focal cerebral ischemia was
      induced in male rats by middle cerebral artery occlusion (MCAO) and cerebral
      cortices were collected 24 h after MCAO. Cerebral ischemia significantly
      increased infarct volume. RT-PCR and Western blot analyses showed that MCAO
      injury induced a decrease of calbindin expression. Moreover, immunohistochemical
      staining showed that the number of calbindin-positive cells decreased in ischemic
      regions of MCAO-operated animals. In cultured hippocampal-derived cell lines,
      glutamate exposure increased intracellular Ca(2+) concentrations and decreased
      calbindin expression. Taken together, both in vivo and in vitro results
      demonstrated decreases of calbindin after neuronal cell injury. These results
      suggest that decreases of calbindin in ischemic brain injury contribute to
      neuronal cell death. 

PMID- 24106511
TI  - Proteomic analysis of liver in miniature pigs according to developmental stages
      using two-dimensional electrophoresis and matrix-assisted laser
      desorption/ionization-time of flight mass spectrometry.
AB  - Due to the shortage of human organ donors for transplant, various studies of
      xenotransplantation, or the use of animal organs instead of human organs, have
      been carried out. The organs of porcine are thought to be safer and of a more
      suitable size for xenotransplantationthan those of nonhuman primates.
      Understanding the levels of expression of proteins, and their post-translational
      regulation, would be very practical between different species and among
      developing stages, though the molecular profiling for xenotransplantation has
      been rarely studied for porcine, while that of human and rodent is well known.
      Here, in this present study, we report protein regulation of the developing
      stages of liver (4-day old neonate, 19-day old piglet and 14-month old adult
      miniature pigs) using 2-DE and MALDI-TOF. From images of the three different
      stages, a total of 8 spotswhich were differently regulated were identified, and 5
      spots were identified with MALDI-TOF MS. The data presented within this study
      provides critical direction relating to the development of livers of miniature
      pigs, which will assist future proteome analysis of the liver, and advance our
      understanding of the hurdles facing xenotransplantaion. 

PMID- 24106512
TI  - Effects of estrogen on food intake, serum leptin levels and leptin mRNA
      expression in adipose tissue of female rats.
AB  - The integration of metabolism and reproduction involves complex interactions of
      hypothalamic neuropeptides with metabolic hormones, fuels, and sex steroids. Of
      these, estrogen influences food intake, body weight, and the accumulation and
      distribution of adipose tissue. In this study, the effects of estrogen on food
      intake, serum leptin levels, and leptin mRNA expression were evaluated in
      ovariectomized rats. Seven-week-old female Wistar-Imamichi rats were
      ovariectomized and divided into three treatment groups: group 1 (the control
      group) received sesame oil, group 2 was given 17beta-estradiol benzoate, and
      group 3 received 17beta-estradiol benzoate plus progesterone. The body weight and
      food consumption of each rat were determined daily. Serum leptin levels and
      leptin mRNA expression were measured by ELISA and quantitative RT-PCR,
      respectively. Food consumption in the control group was significantly higher
      (P<0.05) than that in groups 2 and 3, although body weight did not significantly
      differ among the three groups. The serum leptin concentration and leptin mRNA
      expression were significantly higher (P<0.05) in groups 2 and 3 than in group 1,
      but no significant difference existed between groups 2 and 3. In conclusion,
      estrogen influenced food intake via the modulation of leptin signaling pathway in
      ovariectomized rats. 

PMID- 24106513
TI  - Development of osteoporosis animal model using micropigs.
AB  - Osteoporosis is a known major health problem and a serious disease of the bone,
      there has been a great need to develop more and newer animal models for this
      disease. Among animal models used for testing drug efficacy, the minipig model
      has become useful and effective due to its close similarity with humans
      (validity), particularly with the pharmacokinetics of compounds via subcutaneous
      administration, the structure and function of the organs, the morphology of bone
      and the overall metabolic nature. Based on these advantages, we sought to develop
      a new animal model of osteoporosis using micropig, which differs from other
      miniature pigs in the genetic background. Female micropigs were used for the
      induction of a moderate osteoporosis model by bilateral ovariectomy (OVX) and
      compared with shamoperated animals. For osteoporosis evaluation, clinical
      biomarkers such as blood osteocalcin (OSC) and parathyroid hormone (PTH) levels
      were measured, as well as bone mineral density (BMD) using micro-computed
      tomography (micro-CT). Compared to sham, OVX animals have decreased blood OSC
      level, while the blood PTH level increased in blood sera. In addition, we
      observed the significantly decreased BMDs of tibia region in OVX animals. Based
      on these results, we report that the micropig model developed in this study can
      be used to develop a new and effective medical method for diagnosis and treatment
      of osteoporosis. 

PMID- 24106514
TI  - Inhibitory effects of a beta-dunnione compound MB12662 on gastric secretion and
      ulcers.
AB  - The effects of a beta-dunnione compound MB12662 on the gastric secretion and
      ulcers were investigated in rats. In order to assess the effects of MB12662 on
      the gastric secretion and acidity, rats were subjected to pylorus ligation
      operation, and 6 hours later, gastric fluid was collected. Treatment with MB12662
      reduced the gastric fluid volume to 47.3% of control level and increased pH. In
      an alcohol-induced ulcer model, rats were orally administered 3 mL/kg of ethanol,
      and 1 hour later, the ulcer lesions ware measured under a stereomicroscope.
      MB12662 reduced ulcer index in a dose-dependent manner which was much stronger
      than a proton-pump inhibitor pantoprazole. In a stress-induced ulcer model, rats
      were subjected to water-immersion restraint stress, and 5 hours later, the ulcer
      lesions ware examined. MB12662 also attenuated the stress-induced gastric
      lesions, although the efficacy of MB12662 was lower than that of pantoprazole.
      Therefore, it is suggested that MB12662 could be a candidate compound for the
      prevention or treatment of gastric ulcers induced by gastric over-secretion and
      alcoholic hangover. 

PMID- 24106515
TI  - Low-dose amphotericin B and murine dialyzable spleen extracts protect against
      systemic candida infection in mice.
AB  - Candida albicans causes opportunistic systemic infections with high mortality
      (30%-50%). Despite significant nephrotoxicity, amphotericin (AmB) is still used
      for the treatment of this serious fungal infection. Therefore, alternative
      treatments are urgently needed. Dialyzable leukocyte extracts have been used
      successfully to treat patients with mucocutaneous candidiasis, but their
      effectiveness in systemic candidiasis has not been evaluated. In this study, low
      dose AmB (0.1 mg/kg) plus 10 pg of murine dialyzable spleen extracts (mDSE) were
      tested in a systemic candidiasis mouse model. Survival, tissue fungal burden,
      kidney damage, kidney cytokines, and serum levels of IL-6 and hepcidin were
      evaluated. Our results showed that the combined treatment of low-dose AmB plus
      mDSE improved survival and reduced kidney fungal burden and histopathology; these
      effects correlated with increased kidney concentration of IFN- gamma and TGF-
      beta 1, decreased levels of TNF- alpha , IL-6, and IL-10, as well as high levels
      of systemic IL-6 and hepcidin. Low-dose AmB and mDSE synergized to clear the
      infectious agent and reduced tissue damage, confirming the efficacy of a low dose
      of AmB, which might decrease the risk of drug toxicity. Further studies are
      necessary to explore these findings and its implications in future therapeutic
      approaches. 

PMID- 24106516
TI  - Human monoclonal antibodies as a new class of antiinfective compounds.

PMID- 24106517
TI  - Revascularization of transplanted pancreatic islets and role of the
      transplantation site.
AB  - Since the initial reporting of the successful reversal of hyperglycemia through
      the transplantation of pancreatic islets, significant research efforts have been
      conducted in elucidating the process of revascularization and the influence of
      engraftment site on graft function and survival. During the isolation process the
      intrinsic islet vascular networks are destroyed, leading to impaired
      revascularization after transplant. As a result, in some cases a significant
      quantity of the beta cell mass transplanted dies acutely following the infusion
      into the portal vein, the most clinically used site of engraftment. Subsequently,
      despite the majority of patients achieving insulin independence after transplant,
      a proportion of them recommence small, supplemental exogenous insulin over time.
      Herein, this review considers the process of islet revascularization after
      transplant, its limiting factors, and potential strategies to improve this
      critical step. Furthermore, we provide a characterization of alternative
      transplant sites, analyzing the historical evolution and their role towards
      advancing transplant outcomes in both the experimental and clinical settings. 

PMID- 24106519
TI  - A clinical analysis of risk factors for interstitial lung disease in patients
      with idiopathic inflammatory myopathy.
AB  - Interstitial lung disease (ILD) is a common and severe complication of idiopathic
      inflammatory myopathies (IIM). The aim of our study was to identify risk factors
      for ILD by evaluating both clinical and biochemical features in IIM patients with
      or without ILD. From January 2008 to December 2011, medical records of 134 IIM
      patients in our rheumatology unit were reviewed. The patients were divided into
      ILD group (83 patients) and non-ILD group (51 patients). The clinical features
      and laboratory findings were compared. The univariable analyses indicated that
      arthritis/arthralgia (54.2% versus 17.6%, P < 0.05), Mechanic's hand (16.9%
      versus 2.0%, P < 0.05), Raynaud's phenomenon (36.1% versus 2.0%, P < 0.05),
      heliotrope rash (44.6% versus 19.6%, P < 0.05), fever (43.4% versus 21.6%, P <
      0.05), elevated ESR (60.2% versus 35.3%, P < 0.05), elevated CRP (55.4% versus
      31.4%, P < 0.05), or anti-Jo-1 antibody (20.5% versus 5.9%, P < 0.05) were risk
      factors for developing ILD in IIM. Multivariable unconditional logistic
      regression analysis that showed arthritis/arthralgia (OR 7.1, 95% CI 2.8-18.1),
      Raynaud's phenomenon (OR 29.1, 95% CI 3.6-233.7), and amyopathic dermatomyositis
      (ADM) (OR 20.2, 95% CI 2.4-171.2) were the independent risk factors for
      developing ILD in IIM. 

PMID- 24106520
TI  - Increased IL-33 in synovial fluid and paired serum is associated with disease
      activity and autoantibodies in rheumatoid arthritis.
AB  - OBJECTIVES: IL-33, a newly found cytokine which is involved in joint
      inflammation, could be blocked by a decoy receptor-sST2. The expression and
      correlation of IL-33 and sST2 in rheumatoid arthritis (RA) are of great interest.
      METHODS: Synovial fluid (SF) was obtained from 120 RA and 30 osteoarthritis (OA)
      patients, and paired sera were collected from 54 of these RA patients. The levels
      of IL-33 and sST2 were measured by ELISA. RESULTS: SF IL-33 was significantly
      higher in RA than in OA, which was correlated with disease activity score 28,
      erythrocyte sedimentation rate, rheumatoid factor (RF)-IgM, RF-IgG, glucose
      phosphate isomerase (GPI), and immunoglobulin. Serum IL-33 was correlated
      positively with SF IL-33 in RA. Furthermore, it was correlated with RF-IgM and
      GPI. sST2 was partly detectable in RA (13 out of 54, 24.1%), while not in OA.
      Serum sST2 in RA had no significant correlation with serum IL-33 or SF IL-33.
      However, SFs from both RA and OA patients did not express sST2. CONCLUSIONS: This
      study supported that IL-33 played an important role in the local pathogenesis of
      RA. Considering the tight correlation between IL-33 and clinical features, it may
      become a new target of local treatment.

PMID- 24106518
TI  - Immunotherapy treatments of warm autoimmune hemolytic anemia.
AB  - Warm autoimmune hemolytic anemia (WAIHA) is one of four clinical types of
      autoimmune hemolytic anemia (AIHA), with the characteristics of autoantibodies
      maximally active at body temperature. It produces a variable anemia-sometimes
      mild and sometimes severe. With respect to the absence or presence of an
      underlying condition, WAIHA is either idiopathic (primary) or secondary, which
      determines the treatment strategies in practice. Conventional treatments include
      immune suppression with corticosteroids and, in some cases, splenectomy. In
      recent years, the number of clinical studies with monoclonal antibodies and
      immunosuppressants in the treatment of WAIHA increased as the knowledge of
      autoimmunity mechanisms extended. This thread of developing new tools of treating
      WAIHA is well exemplified with the success in using anti-CD20 monoclonal
      antibody, Rituximab. Following this success, other treatment methods based on the
      immune mechanisms of WAIHA have emerged. We reviewed these newly developed
      immunotherapy treatments here in order to provide the clinicians with more
      options in selecting the best therapy for patients with WAIHA, hoping to
      stimulate researchers to find more novel immunotherapy strategies. 

PMID- 24106521
TI  - Electroacupuncture Stimulation at CV12 Inhibits Gastric Motility via TRPV1
      Receptor.
AB  - Gastric dysmotility is one of the major pathophysiological factors in functional
      gastrointestinal disorders. Acupuncture, as one of the alternative approaches, is
      efficacious in the treatment of gastrointestinal motility disorders; however, the
      mechanism underlying its action is unclear. In the present study, we used both
      capsazepine, a TRPV1 antagonist, and TRPV1 knockout mice. Animals were divided
      into wild-type group (WT), capsazepine injection group (CZP, 0.5 mg/kg, i.p.),
      and TRPV1 knockout mice group (TRPV1(-/-)). Each of these three groups was
      divided into three subgroups, which were subjected to EA stimulation at acupoint
      Zhongwan (CV12) at a different intensity (1, 2, or 4 mA). We demonstrated that
      electroacupuncture at Zhongwan (CV12) markedly inhibited gastric motility at 2
      and 4 mA in an intensity-dependent manner in wild-type mice. The inhibitory
      effect was also observed in capsazepine-injected and TRPV1(-/-) mice but was no
      longer intensity dependent, indicating that TRPV1 is partially involved in the
      electroacupuncture-mediated modulation of gastric motility. 

PMID- 24106522
TI  - Exercise ameliorates renal cell apoptosis in chronic kidney disease by
      intervening in the intrinsic and the extrinsic apoptotic pathways in a rat model.
AB  - We hypothesized that doxorubicin (DR) induced chronic kidney disease (CKD) could
      trigger the intrinsic and the extrinsic renal cell apoptotic pathways, while
      treadmill exercise could help prevent adverse effects. Male Sprague-Dawley rats
      were subjected to treadmill running exercise at a speed of 30 m/min, 30 or 60
      min/day, 3 times per week, for a total period of 11 weeks. The physiological and
      biochemical parameters were seen substantially improved (DR-CKD control, 30 min,
      60 min exercise): the ratio of kidney weight/body weight (0.89, 0.74, and 0.72);
      the WBC (1.35, 1.08, and 1.42 * 10(4) cells/ MU L); RBC (5.30, 6.38, and 6.26 *
      10(6) cells/ MU L); the platelet count (15.1, 12.8, and 11.3 * 10(5)/ MU L);
      serum cholesterol (659, 360, and 75 mg/dL); serum triglyceride (542, 263, and 211
      mg/dL); BUN (37, 25, and 22 mg/dL). Bcl-2 and intramitochondrial cytochrome c
      were upregulated, while the levels of Bax, SOD, MDA, cleaved caspases 9, 3, 8,
      12, and calpain were all downregulated in DRCKD groups with exercise. CHOP
      (GADD153) and GRP78 were totally unaffected. FAS (CD95) was only slightly
      suppressed in the 60 min exercise DRCKD group. Conclusively, exercise can
      ameliorate CKD through the regulation of the intrinsic and extrinsic apoptosis
      pathways. The 60 min exercise yields more beneficial effect than the 30 min
      counterpart. 

PMID- 24106523
TI  - Computer aided detection of breast density and mass, and visualization of other
      breast anatomical regions on mammograms using graph cuts.
AB  - Breast cancer mostly arises from the glandular (dense) region of the breast.
      Consequently, breast density has been found to be a strong indicator for breast
      cancer risk. Therefore, there is a need to develop a system which can segment or
      classify dense breast areas. In a dense breast, the sensitivity of mammography
      for the early detection of breast cancer is reduced. It is difficult to detect a
      mass in a breast that is dense. Therefore, a computerized method to separate the
      existence of a mass from the glandular tissues becomes an important task.
      Moreover, if the segmentation results provide more precise demarcation enabling
      the visualization of the breast anatomical regions, it could also assist in the
      detection of architectural distortion or asymmetry. This study attempts to
      segment the dense areas of the breast and the existence of a mass and to
      visualize other breast regions (skin-air interface, uncompressed fat, compressed
      fat, and glandular) in a system. The graph cuts (GC) segmentation technique is
      proposed. Multiselection of seed labels has been chosen to provide the hard
      constraint for segmentation of the different parts. The results are promising. A
      strong correlation (r = 0.93) was observed between the segmented dense breast
      areas detected and radiological ground truth. 

PMID- 24106524
TI  - Automatic evaluation of progression angle and fetal head station through
      intrapartum echographic monitoring.
AB  - Labor progression is routinely assessed through transvaginal digital inspections,
      meaning that the clinical decisions taken during the most delicate phase of
      pregnancy are subjective and scarcely supported by technological devices. In
      response to such inadequacies, we combined intrapartum echographic acquisitions
      with advanced tracking algorithms in a new method for noninvasive, quantitative,
      and automatic monitoring of labor. Aim of this work is the preliminary clinical
      validation and accuracy evaluation of our automatic algorithm in assessing
      progression angle (PA) and fetal head station (FHS). A cohort of 10 parturients
      underwent conventional labor management, with additional translabial echographic
      examinations after each uterine contraction. PA and FHS were evaluated by our
      automatic algorithm on the acquired images. Additionally, an experienced clinical
      sonographer, blinded regarding the algorithm results, quantified on the same
      acquisitions of the two parameters through manual contouring, which were
      considered as the standard reference in the evaluation of automatic algorithm and
      routine method accuracies. The automatic algorithm (mean error +/- 2SD) provided
      a global accuracy of 0.9 +/- 4.0 mm for FHS and 4 degrees  +/- 9 degrees  for PA,
      which is far above the diagnostic ability shown by the routine method, and
      therefore it resulted in a reliable method for earlier identification of abnormal
      labor patterns in support of clinical decisions. 

PMID- 24106525
TI  - A microfluidic device for on-chip agarose microbead generation with ultralow
      reagent consumption.
AB  - Water-in-oil microdroplets offer microreactors for compartmentalized biochemical
      reactions with high throughput. Recently, the combination with a sol-gel switch
      ability, using agarose-in-oil microdroplets, has increased the range of possible
      applications, allowing for example the capture of amplicons in the gel phase for
      the preservation of monoclonality during a PCR reaction. Here, we report a new
      method for generating such agarose-in-oil microdroplets on a microfluidic device,
      with minimized inlet dead volume, on-chip cooling, and in situ monitoring of
      biochemical reactions within the gelified microbeads. We used a flow-focusing
      microchannel network and successfully generated agarose microdroplets at room
      temperature using the "push-pull" method. This method consists in pushing the oil
      continuous phase only, while suction is applied to the device outlet. The agarose
      phase present at the inlet is thus aspirated in the device, and segmented in
      microdroplets. The cooling system consists of two copper wires embedded in the
      microfluidic device. The transition from agarose microdroplets to microbeads
      provides additional stability and facilitated manipulation. We demonstrate the
      potential of this method by performing on-chip a temperature-triggered DNA
      isothermal amplification in agarose microbeads. Our device thus provides a new
      way to generate microbeads with high throughput and no dead volume for
      biochemical applications. 

PMID- 24106526
TI  - Nano-islands integrated evanescence-based lab-on-a-chip on silica-on-silicon and
      polydimethylsiloxane hybrid platform for detection of recombinant growth hormone.
AB  - Integration of nano-materials in optical microfluidic devices facilitates the
      realization of miniaturized analytical systems with enhanced sensing abilities
      for biological and chemical substances. In this work, a novel method of
      integration of gold nano-islands in a silica-on-silicon-polydimethylsiloxane
      microfluidic device is reported. The device works based on the nano-enhanced
      evanescence technique achieved by interacting the evanescent tail of propagating
      wave with the gold nano-islands integrated on the core of the waveguide resulting
      in the modification of the propagating UV-visible spectrum. The biosensing
      ability of the device is investigated by finite-difference time-domain simulation
      with a simplified model of the device. The performance of the proposed device is
      demonstrated for the detection of recombinant growth hormone based on antibody
      antigen interaction. 

PMID- 24106527
TI  - Bronchopleural fistula.

PMID- 24106528
TI  - Uterine arteriovenous malformation with sudden heavy vaginal hemmorhage.
AB  - Dysfunctional uterine bleeding (DUB) is a common presentation in the emergency
      department and has a wide differential. Most presentations of DUB are in
      hemodynamically stable patients and can be evaluated as an outpatient. Uterine
      arteriovenous malformation (AVM) is one presentation that can result in a life
      threatening medical emergency with unexpected sudden and massive vaginal
      bleeding. We describe a case of a 24-year-old female with sudden heavy vaginal
      bleeding requiring a blood transfusion, ultrasound evidence of uterine AVM, and a
      treatment method of expectant management using an intrauterine device in an
      attempt to preserve fertility. 

PMID- 24106529
TI  - Appendicitis Diagnosed by Emergency Physician Performed Point-of-Care
      Transvaginal Ultrasound: Case Series.
AB  - Lower abdominal pain in females of reproductive age continues to be a diagnostic
      dilemma for the emergency physician (EP). Point-of-care ultrasound (US) allows
      for rapid, accurate, and safe evaluation of abdominal and pelvic pain in both the
      pregnant and non-pregnant patient. We present 3 cases of females presenting with
      right lower quadrant and adnexal tenderness where transvaginal ultrasonography
      revealed acute appendicitis. The discussion focuses on the use of EP- performed
      transvaginal US in gynecologic and intra-abdominal pathology and discusses the
      use of a staged approach to evaluation using US and computed tomography, as
      indicated. 

PMID- 24106530
TI  - Cephalohematoma in a patient with ehlers-danlos syndrome.
AB  - Ehlers-Danlos syndrome is a rarely encountered connective tissue disorder
      characterized by skin hyper-elasticity, joint hyper-flexibility, and vasculature
      fragility. We report a 41-year-old female presenting with scalp swelling
      following minor head trauma. The patient presented with a large cephalohematoma
      that despite compressive measures and Factor IX administration continued to
      progress, necessitating transfer for definitive surgical intervention. The
      patient underwent surgical evacuation of approximately 1 liter of blood, followed
      by drain placement and compression dressing. This case underscores the importance
      for emergency physicians to recognize the potential vascular catastrophes these
      patients may present with following even minor injury. 

PMID- 24106531
TI  - Early presentation of buried bumper syndrome.
AB  - Percutaneous endoscopic gastrostomy (PEG) is a relatively safe and effective
      method of providing nutrition to patients with neurologic deficits or proximal
      gastrointestinal pathology. Complications that follow this common procedure
      include dislodgement, dysfunction, infection and aspiration. The "Buried Bumper
      Syndrome" (BBS) is an infrequent and late complication of PEG tubes that can
      result in tube dysfunction, gastric perforation, bleeding, peritonitis or death.
      The emergency physician should be aware of historical and exam features that
      suggest BBS and distinguish it from other, more benign, PEG-tube related
      complaints. We report a case of a woman presenting with BBS 3 weeks after having
      a PEG tube placed. 

PMID- 24106532
TI  - "I Can't Walk!" Acute Thrombosis of Descending Aorta Causing Paraplegia.
AB  - A 50-year-old man presented to the emergency department (ED) with acute,
      bilateral lower extremity weakness and loss of sensation, as well as absent
      pulses bilaterally. Computed tomography angiography showed complete occlusion of
      the aorta below the inferior mesenteric artery, extending to the iliac
      bifurcations. Echocardiographic findings showed severe systolic dysfunction
      (ejection fraction of 15%) and cryptic cardiogenic shock in spite of stable vital
      signs. Prior to early operative intervention, an early goal-oriented hemodynamic
      strategy of shock management resulted in the resolution of motor and sensory
      deficits.After definitive surgical intervention, the patient was discharged
      neurologically intact. Acute aortic occlusion is frequently accompanied by
      myocardial dysfunction, which can be from mild to severe. The most severe form
      can even occur with normal vital signs or occult cardiogenic shock. Early
      detection and goal-directed preoperative hemodynamic optimization, along with
      surgical intervention in the ED, is required to optimize outcomes. 

PMID- 24106533
TI  - Pylephlebitis in a previously healthy emergency department patient with
      appendicitis.
AB  - Pylephlebitis is a septic thrombophlebitis of the portal vein that is associated
      with multiple suppurative abdominal infections, such as diverticulitis,
      appendicitis, cholangitis, and cholecystitis. We describe a case of pylephlebitis
      in a patient with fever and diffuse, poorly localized abdominal pain who was
      eventually diagnosed with appendicitis. We aim to increase awareness of this
      condition among emergency physicians, as timely initiation of antibiotics and
      expedited surgical resection may improve outcomes in this potentially fatal
      disease. 

PMID- 24106534
TI  - Parenteral hydrocarbon injection and associated toxicities: two case reports.

PMID- 24106535
TI  - Diaphragmatic rupture secondary to blunt thoracic trauma.

PMID- 24106536
TI  - Vaginal foreign bodies and child sexual abuse: an important consideration.
AB  - Vaginal foreign bodies are a complaint occasionally encountered in pediatric
      clinics and emergency departments, and when pediatric patients present with a
      vaginal foreign body sexual abuse may not be considered. We describe two children
      with vaginal foreign bodies who were found to have been sexually abused. Each
      child had a discharge positive for a sexually transmitted infection despite no
      disclosure or allegation of abuse. We recommend that all pre-pubertal girls who
      present with a vaginal foreign body should be considered as possible victims of
      sexual abuse and should receive a sexual abuse history and testing for sexually
      transmitted infections. 

PMID- 24106537
TI  - Complication with intraosseous access: scandinavian users' experience.
AB  - INTRODUCTION: Intraosseous access (IO) is indicated if vascular access cannot be
      quickly established during resuscitation. Complication rates are estimated to be
      low, based on small patient series, model or cadaver studies, and case reports.
      However, user experience with IO use in real-life emergency situations might
      differ from the results in the controlled environment of model studies and small
      patient series. We performed a survey of IO use in real-life emergency situations
      to assess users' experiences of complications. METHODS: An online questionnaire
      was sent to Scandinavian emergency physicians, anesthesiologists and
      pediatricians. RESULTS: 1,802 clinical cases of IO use was reported by n=386
      responders. Commonly reported complications with establishing IO access were
      patient discomfort/pain (7.1%), difficulties with penetration of periosteum with
      IO needle (10.3%), difficulties with aspiration of bone marrow (12.3%), and
      bended/broken needle (4.0%). When using an established IO access the reported
      complications were difficulties with injection fluid and drugs after IO insertion
      (7.4%), slow infusion (despite use of pressure bag) (8.8%), displacement after
      insertion (8.5%), and extravasation (3.7%). Compartment syndrome and
      osteomyelitis occurred in 0.6% and 0.4% of cases respectively. CONCLUSION: In
      users' recollection of real-life IO use, perceived complications were more
      frequent than usually reported from model studies. The perceived difficulties
      with using IO could affect the willingness of medical staff to use IO. Therefore,
      user experience should be addressed both in education of how to use, and research
      and development of IOs.

PMID- 24106538
TI  - Uterine rupture due to invasive metastatic gestational trophoblastic neoplasm.
AB  - While complete molar pregnancies are rare, they are wrought with a host of
      potential complications to include invasive gestational trophoblastic neoplasia.
      Persistent gestational trophoblastic disease following molar pregnancy is a
      potentially fatal complication that must be recognized early and treated
      aggressively for both immediate and long-term recovery. We present the case of a
      21-year-old woman with abdominal pain and presyncope 1 month after a molar
      pregnancy with a subsequent uterine rupture due to invasive gestational
      trophoblastic neoplasm. We will discuss the complications of molar pregnancies
      including the risks and management of invasive, metastatic gestational
      trophoblastic neoplasia. 

PMID- 24106539
TI  - Levamisole contaminated cocaine induced cutaneous vasculitis syndrome.

PMID- 24106540
TI  - Bullous lung disease.

PMID- 24106541
TI  - Asymmetrical bilateral hip dislocation.

PMID- 24106542
TI  - Predictive value of initial triage vital signs for critically ill older adults.
AB  - INTRODUCTION: Triage of patients is critical to patient safety, yet no clear
      information exists as to the utility of initial vital signs in identifying
      critically ill older emergency department (ED) patients. The objective of this
      study is to evaluate a set of initial vital sign thresholds as predictors of
      severe illness and injury among older adults presenting to the ED. METHODS: We
      reviewed all visits by patients aged 75 and older seen during 2007 at an academic
      ED serving a large community of older adults. Patients' charts were abstracted
      for demographic and clinical information including vital signs, via automated
      electronic methods. We used bivariate analysis to investigate the relationship
      between vital sign abnormalities and severe illness or injury, defined as
      intensive care unit (ICU) admission or ED death. In addition, we calculated
      likelihood ratios for normal and abnormal vital signs in predicting severe
      illness or injury. RESULTS: 4,873 visits by patients aged 75 and above were made
      to the ED during 2007, and of these 3,848 had a complete set of triage vital
      signs. For these elderly patients, the sensitivity and specificity of an abnormal
      vital sign taken at triage for predicting death or admission to an ICU were 73%
      (66,81) and 50% (48,52) respectively (positive likelihood ratio 1.47 (1.30,1.60);
      negative likelihood ratio 0.54 (0.30,0.60). CONCLUSION: Emergency provider
      assessment and triage scores that rely primarily on initial vital signs are
      likely to miss a substantial portion of critically ill older adults.

PMID- 24106543
TI  - Sexual assault training in emergency medicine residencies: a survey of program
      directors.
AB  - INTRODUCTION: There is currently no standard forensic medicine training program
      for emergency medicine residents. In the advent of sexual assault nurse examiner
      (SANE) programs aimed at improving the quality of care for sexual assault
      victims, it is also unclear how these programs impact emergency medicine (EM)
      resident forensic medicine training. The purpose of this study was to gather
      information on EM residency programs' training in the care of sexual assault
      patients and determine what impact SANE programs may have on the experience of EM
      resident training from the perspective of residency program directors (PDs).
      METHODS: This was a cross-sectional survey. The study cohort was all residency
      PDs from approved EM residency training programs who completed a closed-response
      self-administered survey electronically. RESULTS: We sent surveys to 152 PDs, and
      71 responded for an overall response rate of 47%. Twenty-two PDs (31%) reported
      that their residency does not require procedural competency for the sexual
      assault exam, and 29 (41%) reported their residents are required only to observe
      sexual assault exam completion to demonstrate competency. Residency PDs were
      asked how their programs established resident requirements for sexual assault
      exams. Thirty-seven PDs (52%) did not know how their sexual assault exam
      requirement was established. CONCLUSION: More than half of residency PDs did not
      know how their sexual assault guidelines were established, and few were based
      upon recommendations from the literature. There is no clear consensus as to how
      PDs view the effect of SANE programs on resident competency with the sexual
      assault exam. This study highlights both a need for increased awareness of EM
      resident sexual assault education nationally and also a possible need for a
      training curriculum defining guidelines for EM residents performing sexual
      assault exams.

PMID- 24106544
TI  - Emergency physicians' knowledge of cannabinoid designer drugs.
AB  - INTRODUCTION: The use of synthetic drugs of abuse in the United States has grown
      in the last few years, with little information available on how much physicians
      know about these drugs and how they are treating patients using them. The
      objective of this study was to assess emergency physician (EP) knowledge of
      synthetic cannabinoids (SC). METHODS: A self-administered internet-based survey
      of resident and attending EPs at a large urban emergency department (ED) was
      administered to assess familiarity with the terms Spice or K2 and basic knowledge
      of SC, and to describe some practice patterns when managing SC intoxication in
      the ED. RESULTS: Of the 83 physicians invited to participate, 73 (88%) completed
      surveys. The terms "Spice" and "K2" for SC were known to 25/73 (34%) and 36/73
      (49%) of respondents. Knowledge of SC came most commonly (72%) from non-medical
      sources, with lay publications and the internet providing most respondents with
      information. Among those with previous knowledge of synthetic cannabinoids, 25%
      were not aware that SC are synthetic drugs, and 17% did not know they are
      chemically most similar to marijuana. Among all participants, 80% felt unprepared
      caring for a patient in the ED who had used synthetic cannabinoids. CONCLUSION:
      Clinically active EPs are unfamiliar with synthetic cannabinoids. Even those who
      stated they had heard of synthetic cannabinoids answered poorly on basic
      knowledge questions. More education is needed among EPs of all ages and levels of
      training on synthetic cannabinoids.

PMID- 24106545
TI  - English-based Pediatric Emergency Medicine Software Improves Physician Test
      Performance on Common Pediatric Emergencies: A Multicenter Study in Vietnam.
AB  - INTRODUCTION: Global health agencies and the Vietnam Ministry of Health have
      identified pediatric emergency care and health information technology as high
      priority goals. Clinical decision support (CDS) software provides physicians with
      access to current literature to answer clinical queries, but there is limited
      impact data in developing countries. We hypothesized that Vietnamese physicians
      will demonstrate improved test performance on common pediatric emergencies using
      CDS technologies despite being in English. METHODS: This multicenter,
      prospective, pretest-posttest study was conducted in 11 Vietnamese hospitals
      enrolled a convenience sample of physicians who attended an 80-minute software
      training on a pediatric CDS software (PEMSoft). Two multiple-choice exams (A, B)
      were administered before and after the session. Participants, who received Test A
      as a pretest, received Test B as a posttest, and vice versa. Participants used
      the CDS software for the posttest. The primary outcome measure was the mean
      percentage difference in physician scores between the pretest and posttest, as
      calculated by a paired, two-tailed t-test. RESULTS: For the 203 participants, the
      mean pretest, posttest, and improvement scores were 37% (95% CI: 35-38%), 70%
      (95% CI: 68-72%), and 33% (95% CI: 30-36%), respectively, with p<0.0001. This
      represents an 89% improvement over baseline. Subgroup analysis of practice
      setting, clinical experience, and comfort level with written English and
      computers showed that all subgroups equivalently improved their test scores.
      CONCLUSION: After brief training, Vietnamese physicians can effectively use an
      English-based CDS software based on improved performance on a written clinical
      exam. Given this rapid improvement, CDS technologies may serve as a
      transformative tool in resource-poor environments.

PMID- 24106546
TI  - Emergency Medicine in Guyana: Lessons from Developing the Country's First Degree
      conferring Residency Program.
AB  - INTRODUCTION: Academic departments of emergency medicine are becoming
      increasingly involved in assisting with the development of long-term emergency
      medicine training programs in low and middle-income countries. This article
      presents our 10-year experience working with local partners to improve emergency
      medical care education in Guyana. METHODS: The Vanderbilt Department of Emergency
      Medicine has collaborated with the Georgetown Public Hospital Corporation on the
      development of Emergency Medicine skills followed by the implementation of an
      emergency medicine residency training program. Residency development included a
      needs assessment, proposed curriculum, internal and external partnerships,
      University of Guyana and Ministry of Health approval, and funding. RESULTS: In
      our experience, we have found that our successful program initiation was due in
      large part to the pre-existing interest of several local partners and followed by
      long-term involvement within the country. As a newer specialty without
      significant local expertise, resident educational needs mandated a locally
      present full time EM trained attending to serve as the program director. Both
      external and internal funding was required to achieve this goal. Local
      educational efforts were best supplemented by robust distance learning. The
      program was developed to conform to local academic standards and to train the
      residents to the level of consultant physicians. Despite the best preparations,
      future challenges remain. CONCLUSION: While every program has unique challenges,
      it is likely many of the issues we have faced are generalizable to other settings
      and will be useful to other programs considering or currently conducting this
      type of collaborative project.

PMID- 24106547
TI  - Electronic Prehospital Records are Often Unavailable for Emergency Department
      Medical Decision Making.
AB  - INTRODUCTION: To determine emergency physician (EP) opinions of prehospital
      patient care reports (PCRs) and whether such reports are available at the time of
      emergency department (ED) medical decision-making. METHODS: Prospective, cross
      sectional, electronic web-based survey of EPs regarding preferences and
      availability of prehospital PCRs at the time of ED medical decision-making.
      RESULTS: We sent the survey to 1,932 EPs via 4 American College of Emergency
      Physicians (ACEP) email lists. As a result, 228 (11.8%) of email list members
      from 31 states and the District of Columbia completed the survey. Most
      respondents preferred electronic prehospital PCRs as opposed to handwritten
      prehospital PCRs (52.2% [95% confidence interval (CI): 49.1, 55.3] vs. 17.1%
      [95%CI: 11.7, 22.5]). The remaining respondents (30.5% [95%CI: 26.0, 35.0]) had
      no preference or had seen only one type of PCR. Of the respondents, 45.6% [95%CI:
      42.1, 48.7] stated PCRs were "very important" while 43.0% [95% CI: 39.3, 46.7]
      rated PCRs as "important" in their ED practice. Most respondents (79.6% [95%CI:
      76.5, 82.7]) reported electronic prehospital PCRs were available <=50% of the
      time for medical decision-making while 20.4% [95%CI: 9.2, 31.6] reported that
      electronic prehospital PCRs were available > 50% of the time (P=0.00). A majority
      of participants (77.6% [95%CI: 74.5, 80.7]) reported that handwritten prehospital
      PCRs were available >= 50% while 22.4% [95%CI: 11.8, 33.0] of the time for
      medical decision-making (P=0.00). CONCLUSION: EPs in this study felt that
      prehospital PCRs were important to their ED practice and preferred electronic
      prehospital PCRs over handwritten PCRs. However, most electronic prehospital PCRs
      were unavailable at the time of ED medical decision-making. Although handwritten
      prehospital PCRs were more readily available, legibility and accuracy were
      reported concerns. This study suggest that strategies should be devised to
      improve the overall accuracy of PCRs and assure that electronic prehospital PCRs
      are delivered to the receiving ED in time for consideration in ED medical
      decision-making.

PMID- 24106548
TI  - Reducing ambulance diversion at hospital and regional levels: systemic review of
      insights from simulation models.
AB  - INTRODUCTION: Optimal solutions for reducing diversion without worsening
      emergency department (ED) crowding are unclear. We performed a systematic review
      of published simulation studies to identify: 1) the tradeoff between ambulance
      diversion and ED wait times; 2) the predicted impact of patient flow
      interventions on reducing diversion; and 3) the optimal regional strategy for
      reducing diversion. METHODS:  DATA SOURCES: Systematic review of articles using
      MEDLINE, Inspec, Scopus. Additional studies identified through bibliography
      review, Google Scholar, and scientific conference proceedings. STUDY SELECTION:
      Only simulations modeling ambulance diversion as a result of ED crowding or
      inpatient capacity problems were included. DATA EXTRACTION: Independent
      extraction by two authors using predefined data fields. RESULTS: We identified
      5,116 potentially relevant records; 10 studies met inclusion criteria. In models
      that quantified the relationship between ED throughput times and diversion,
      diversion was found to only minimally improve ED waiting room times. Adding
      holding units for inpatient boarders and ED-based fast tracks, improving lab
      turnaround times, and smoothing elective surgery caseloads were found to reduce
      diversion considerably. While two models found a cooperative agreement between
      hospitals is necessary to prevent defensive diversion behavior by a hospital when
      a nearby hospital goes on diversion, one model found there may be more optimal
      solutions for reducing region wide wait times than a regional ban on diversion.
      CONCLUSION: Smoothing elective surgery caseloads, adding ED fast tracks as well
      as holding units for inpatient boarders, improving ED lab turnaround times, and
      implementing regional cooperative agreements among hospitals are promising
      avenues for reducing diversion.

PMID- 24106549
TI  - In-flight Medical Emergencies.
AB  - INTRODUCTION: Research and data regarding in-flight medical emergencies during
      commercial air travel are lacking. Although volunteer medical professionals are
      often called upon to assist, there are no guidelines or best practices to guide
      their actions. This paper reviews the literature quantifying and categorizing in
      flight medical incidents, discusses the unique challenges posed by the in-flight
      environment, evaluates the legal aspects of volunteering to provide care, and
      suggests an approach to managing specific conditions at 30,000 feet. METHODS: We
      conducted a MEDLINE search using search terms relevant to aviation medical
      emergencies and flight physiology. The reference lists of selected articles were
      reviewed to identify additional studies. RESULTS: While incidence studies were
      limited by data availability, syncope, gastrointestinal upset, and respiratory
      complaints were among the most common medical events reported. Chest pain and
      cardiovascular events were commonly associated with flight diversion. CONCLUSION:
      When in-flight medical emergencies occur, volunteer physicians should have
      knowledge about the most common in-flight medical incidents, know what is
      available in on-board emergency medical kits, coordinate their therapy with the
      flight crew and remote resources, and provide care within their scope of
      practice.

PMID- 24106550
TI  - Ultrasound-guided Intraarticular Hip Injection for Osteoarthritis Pain in the
      Emergency Department.
AB  - Ultrasound-guided intraarticular hip corticosteroid injections may be useful for
      emergency care providers treating patients with painful exacerbations of
      osteoarthritis of the hip. Corticosteroid injection is widely recommended as a
      first-line treatment for painful osteoarthritis of the hip. Bedside ultrasound is
      readily available in most emergency departments; however, using ultrasound to
      guide therapeutic hip injections has not yet been described in emergency
      practice. Herein, we present the first description of a successful emergency
      physician-performed ultrasound-guided hip injection of local anesthetic and
      corticosteroid for pain control in a patient with an acute exacerbation of
      osteoarthritis. 

PMID- 24106551
TI  - Prognostic value of emergency physician performed echocardiography in patients
      with acute pulmonary thromboembolism.
AB  - INTRODUCTION: Pulmonary embolism (PE) is a life-threatening illness with high
      morbidity and mortality. Echocardiography (ECG) plays an important role in the
      early identification of right ventricular (RV) dysfunction, making it a helpful
      tool in identifying hemodynamically stable patients affected by PE with a higher
      mortality risk. The purpose of this study was to evaluate if one or more ECG
      indexes could predict a short-term evolution towards RV dysfunction. METHODS: We
      selected all patients consecutively admitted to the Careggi Hospital Emergency
      Department with the clinical suspicion of PE, confirmed by computed tomography
      angiography prior to enrollment. Subsequently, properly trained emergency
      physicians acquired a complete ECG to measure RV morphological and functional
      indices. For each patient, we recorded if he or she received a fibrinolytic
      treatment, a surgical embolectomy or heparin therapy during the emergency
      department (ED) stay. Then, every patient was re-evaluated with ECG, by the same
      physician, after 1 week in our intensive observation unit and 1 month as
      outpatient in our ED regional referral center for PE. RESULTS: From 2002 to 2007,
      120 consecutive patients affected by PE were evaluated by echocardiography at the
      Careggi Hospital ED. Nine patients (8%) were treated with thrombolytic therapy.
      Six died within 1 week and 4 abandoned the study, while the remaining 110
      survived and were re-evaluated by ECG after 1 week and 1 month. The majority of
      the echocardiographic RV indexes improve mostly in the first 7 days: Acceleration
      Time (AT) from 78+/-14 ms to 117+/-14 ms (p<0.001), Diameter of Inferior Vena
      Cava (DIVC) from 25+/-6 mm to 19+/-5 mm (p<0.001), Tricuspid Annular Plane
      Systolic Excursion (TAPSE) from 16+/-6 mm to 20+/-6 mm (p<0.001). Pulmonary
      Artery Systolic Pressure (PASP) showed a remarkable decrease from 59+/-26 mmHg to
      37+/-9 mmHg, (p<0.001). The measurements of the transverse diameters of both
      ventricles and the respective ratio showed a progressive normalization with a
      reduction of RV diameter, an increase of Left Ventricular (LV) diameter and a
      decrease of RV/LV ratio over time. To evaluate the RV function, the study
      population was divided into 3 groups based on the TAPSE and PASP mean values at
      the admission: Group 1 (68 patients) (TAPSE+/ PASP-), Group 2 (12 patients)
      (TAPSE-/PASP-), and Group 3 (30 patients) (TAPSE-/PASP+). Greater values of AT,
      minor RV diameter, greater LV diameter and a lesser RV/LV ratio were associated
      with a short-term improvement of TAPSE in the Group 2. Instead, in Group 3 the
      only parameter associated with short-term improvement of TAPSE and PASP was the
      treatment with thrombolytic therapy (p<0.0001). CONCLUSION: Greater values of AT,
      minor RV diameter, greater LV diameter and a lesser RV/LV ratio were associated
      with a short-term improvement of TAPSE-/PASP- values. Patients with evidence of
      RV dysfunction (TAPSE-/PASP+), may benefit from thrombolytic therapy to improve a
      short- term RV function. After 1 month, also a decreased DIVC predicted improved
      RV function.

PMID- 24106553
TI  - Need for intervention in families presenting to the emergency department with
      multiple children as patients.
AB  - INTRODUCTION: To assess if families presenting to a pediatric emergency
      department (PED) with multiple children as patients require interventions at the
      same rate as families presenting with a single child. METHODS: This is a
      retrospective chart review looking at PED encounters for families presenting with
      single children versus multiple children as patients. Patients presenting with
      siblings were retrospectively selected from the electronic tracking board, and we
      randomly selected age/gender matched single-patient controls from a comparable
      time period. The primary outcome was a comparison of visit acuity between
      families presenting with single versus multiple children, with the hypothesis
      that families presenting with multiple children as patients would require less
      utilization of services (as a surrogate for acuity). Admission, intravenous fluid
      administration (IVF), planned observation, subspecialty consultation, performance
      of procedures, laboratories and radiographs, administration of prescription
      medications, and prescription medications for home were all recorded and compared
      via chi-squared comparison. We considered 5 interventions (admission,
      subspecialty consultation, performance of procedures, IVF administration, and
      observation > 6 hours) "critical interventions" and compared them separately.
      RESULTS: In our sample of 83 patients from 41 families registering multiple
      children and 248 singleton controls, we found a significant difference in the
      percentage of patients requiring critical interventions (4.8% versus 32.5%, P <
      0.0001). CONCLUSION: Families presenting with multiple children concurrently to
      an ED require critical interventions at a much lower rate than children
      presenting as single patients. Many of these families could be well-served at an
      urgent care or primary care provider.

PMID- 24106552
TI  - Emergency department crowding and time to antibiotic administration in febrile
      infants.
AB  - INTRODUCTION: Early antibiotic administration is recommended in newborns
      presenting with febrile illness to emergency departments (ED) to avert the
      sequelae of serious bacterial infection. Although ED crowding has been associated
      with delays in antibiotic administration in a dedicated pediatric ED, the
      majority of children that receive emergency medical care in the United States
      present to EDs that treat both adult and pediatric emergencies. The purpose of
      this study was to examine the relationship between time to antibiotic
      administration in febrile newborns and crowding in a general ED serving both an
      adult and pediatric population. METHODS: We conducted a retrospective chart
      review of 159 newborns presenting to a general ED between 2005 and 2011 and
      analyzed the association between time to antibiotic administration and ED
      occupancy rate at the time of, prior to, and following infant presentation to the
      ED. RESULTS: We observed delayed and variable time to antibiotic administration
      and found no association between time to antibiotic administration and occupancy
      rate prior to, at the time of, or following infant presentation (p>0.05). ED time
      to antibiotic administration was not associated with hospital length of stay, and
      there was no inpatient mortality. CONCLUSION: Delayed and highly variable time to
      antibiotic treatment in febrile newborns was common but unrelated to ED crowding
      in the general ED study site. Guidelines for time to antibiotic administration in
      this population may reduce variability in ED practice patterns.

PMID- 24106554
TI  - Racial Disparity in Duration of Patient Visits to the Emergency Department:
      Teaching Versus Non-teaching Hospitals.
AB  - INTRODUCTION: The sources of racial disparity in duration of patients' visits to
      emergency departments (EDs) have not been documented well enough for policymakers
      to distinguish patient-related factors from hospital- or area-related factors.
      This study explores the racial disparity in duration of routine visits to EDs at
      teaching and non-teaching hospitals. METHODS: We performed retrospective data
      analyses and multivariate regression analyses to investigate the racial disparity
      in duration of routine ED visits at teaching and non-teaching hospitals. The
      Healthcare Cost and Utilization Project (HCUP) State Emergency Department
      Databases (SEDD) were used in the analyses. The data include 4.3 million routine
      ED visits encountered in Arizona, Massachusetts, and Utah during 2008. We
      computed duration for each visit by taking the difference between admission and
      discharge times. RESULTS: The mean duration for a routine ED visit was 238
      minutes at teaching hospitals and 175 minutes at non-teaching hospitals. There
      were significant variations in duration of routine ED visits across race groups
      at teaching and non-teaching hospitals. The risk-adjusted results show that the
      mean duration of routine ED visits for Black/African American and Asian patients
      when compared to visits for white patients was shorter by 10.0 and 3.4%,
      respectively, at teaching hospitals; and longer by 3.6 and 13.8%, respectively,
      at non-teaching hospitals. Hispanic patients, on average, experienced 8.7% longer
      ED stays when compared to white patients at non-teaching hospitals. CONCLUSION:
      There is significant racial disparity in the duration of routine ED visits,
      especially in non-teaching hospitals where non-White patients experience longer
      ED stays compared to white patients. The variation in duration of routine ED
      visits at teaching hospitals when compared to non-teaching hospitals was smaller
      across race groups.

PMID- 24106555
TI  - Warming intravenous fluids for improved patient comfort in the emergency
      department: a pilot crossover randomized controlled trial.
AB  - INTRODUCTION: The purpose of this study was to test if intravenous (IV) fluids
      warmed to body temperature are associated with greater patient comfort than room
      temperature IV fluids in adult emergency department (ED) patients. METHODS: This
      was a pilot double-blind, crossover, randomized controlled trial. Enrolled
      subjects sequentially received boluses of body temperature (36 degrees C) and
      room temperature (22  degrees C) IV fluid, with the order of boluses randomized.
      Each subject's level of discomfort was assessed prior to and after each bolus,
      using a 10 cm visual analog scale (Discomfort VAS), with higher scores indicating
      greater discomfort. We calculated the change in Discomfort VAS score associated
      with body temperature IV fluid (DeltaVASbody) and room temperature IV fluid
      (DeltaVASroom) by subtracting the score reported before the bolus from the score
      reported after that bolus. We compared changes in Discomfort VAS score with body
      temperature and room temperature IV fluid using the Wilcoxon matched-pairs signed
      rank test. RESULTS: Twenty-seven subjects were included. Treatment with body
      temperature IV fluid was associated with a significant decrease in discomfort
      (median DeltaVASbody: -0.7 cm; interquartile range (IQR): -4.5 cm to +0.4 cm)
      compared to room temperature IV fluid (median DeltaVASroom: +1.2 cm;
      interquartile range: -0.1 cm to + 3.6 cm) (P = 0.001). CONCLUSION: In this small
      trial of adult ED patients, infusing IV fluids warmed to body temperature was
      associated with improved comfort compared to standard, room temperature IV
      fluids.

PMID- 24106556
TI  - Perception of noise by emergency department nurses.
AB  - INTRODUCTION: Noise in the emergency department (ED) may be perceived to be high
      by both patients and nurses alike. This increased noise level is hypothesized to
      be responsible for communication interference and subsequent disruption of
      complex procedures and decision-making. The objective of this study is to
      quantify ambient noise level in an ED while obtaining coincident subjective
      surveys from nurses in the assessment of actual versus perceived noise. METHODS:
      Data collected from surveys of ED nurses on each of 3 different dates revealed
      that sound levels within the selected ED were consistently at or below 70
      decibels (dB) of sound as measured by a sound level meter. This level of sound is
      of the same decibel of normal conversation at a 3-5 foot distance. Nurses
      surveyed overwhelmingly rated noise as "low" or "not loud" irrespective of a
      variance (though predominantly within a 10 dB range) in actual sound decibel
      measurements. RESULTS: Years of experience of work within emergency departments
      proved the most consistent predictor of nurses' opinions on the frequency with
      which noise levels within the ED were louder than they should be, with more
      experienced nurses all ranking noise levels as "frequently" or "always" louder
      than they should be. CONCLUSION: Individual variance existed in how nurses felt
      that noise level affected work function. ED nurses' perception of noise is
      perceived to be low and generally not interfering with their cognitive function.

PMID- 24106557
TI  - Measuring Power in an Emergency Department to Improve Processes and Decrease the
      Length of Stay to their Optimum Value.
AB  - Many emergency departments (EDs) compare themselves to national productivity
      benchmarks, such as the average patients/hour or relative value units
      (RVUs)/hour. Making these comparisons does not provide a tool to determine which
      processes need improvement, most urgently, within the ED to improve efficiency.
      Furthermore, there has been no clear means to determine how to set reasonable
      goals based on the capabilities of the particular ED under study. Determining the
      power of a process is a tool that can provide the ED with these missing pieces of
      information. 

PMID- 24106558
TI  - When a patient declines curative care: management of a ruptured aortic aneurysm.
AB  - The management of major vascular emergencies in the emergency department (ED)
      involves rapid, aggressive resuscitation followed by emergent definitive surgery.
      However, for some patients this traditional approach may not be consistent with
      their goals and values. We explore the appropriate way to determine best
      treatment practices when patients elect to forego curative care in the ED, while
      reviewing such a case. We present the case of a 72-year-old patient who presented
      to the ED with a ruptured abdominal aortic aneurysm, but refused surgery. We
      discuss the transition of the patient from a curative to a comfort care approach
      with appropriate direct referral to hospice from the ED. Using principles of
      autonomy, decision-making capacity, informed consent, prognostication, and goals
      of-care, ED clinicians are best able to align their approach with patients' goals
      and values. 

PMID- 24106560
TI  - In Response to "Education on Prehospital Pain Management: A Follow-up Study".

PMID- 24106559
TI  - Medical-legal Issues in the Agitated Patient: Cases and Caveats.

PMID- 24106561
TI  - In response to "temperature and violent crime in dallas, Texas: relationships and
      implications of climate change".

PMID- 24106562
TI  - Does the application of incisional negative pressure therapy to high-risk wounds
      prevent surgical site complications? A systematic review.
AB  - PURPOSE: The application of incisional negative pressure wound therapy (INPWT) to
      clean, closed surgical incisions is a growing clinical practice. A systematic
      review was conducted to evaluate the effect of INPWT on surgical sites healing by
      primary intention. The primary outcomes of interest are incidence of
      complications (infection, dehiscence, seroma, hematoma, skin necrosis, or
      blistering). METHODS: Two independent reviewers performed a search of the Ovid
      MEDLINE and EMBASE databases from 2006 to 2012 for published articles.
      Supplemental searches were performed using reference lists and conference
      proceedings. Studies were selected for inclusion based on predetermined inclusion
      and exclusion criteria. Data extraction regarding study quality, demographic and
      clinical characteristics, and outcomes was performed independently, and data on
      the incidence of infection was combined using a fixed-effects meta-analysis
      model. RESULTS: Ten (5 randomized controlled trials and 5 observational) studies
      were included, which investigated the outcomes of 626 incisions on 610 patients.
      Six studies compared INPWT with sterile dry dressings (SDDs). The literature
      shows a significant decrease in rates of infection when using INPWT. RESULTS on
      dehiscence do show a decrease in some studies, but results are inconsistent to
      make a conclusion. Because of limited studies, it is difficult to make any
      assertions on seroma, hematoma, and skin necrosis. CONCLUSIONS: This systematic
      review shows possible evidence of a decrease in the incidence of infection with
      application of INPWT. Looking at other variables such as dehiscence, seroma,
      hematoma, and skin necrosis show no consistent data and suggest further studies
      in order for proper recommendations for INPWT.

PMID- 24106564
TI  - Comparison of the Effects of Different Negative Pressure Wound Therapy Modes
      Continuous, Noncontinuous, and With Instillation-on Porcine Excisional Wounds.
AB  - OBJECTIVE: Negative pressure wound therapy (NPWT) can be delivered in continuous
      or noncontinuous modes, while NPWT with instillation (NPWTi) couples NPWT with
      automated delivery and removal of topical wound treatment solutions and
      suspensions. This porcine study compared granulation response of NPWTi
      (instillation foam dressing with saline) to NPWT (standard foam dressing) in
      continuous and noncontinuous modes. METHODS: Full-thickness dorsal excisional
      wounds in pigs were treated with continuous NPWT, intermittent NPWT, dynamic
      (controlled variable) NPWT, and NPWTi with saline (n = 10 per group). Wound
      dimensions were determined from 3D images collected on days 0, 2, 5, and 7. On
      day 7, animals were euthanized and specimens were harvested for histopathological
      review. RESULTS: Average granulation thickness was not statistically different
      among continuous (3.29 +/- 0.33 mm), intermittent (3.03 +/- 0.47 mm), and dynamic
      (3.40 +/- 0.34 mm) NPWT wounds at day 7. Average granulation thickness of NPWTi
      wounds (4.75 +/- 0.54 mm), however, was statistically greater (P < .05) by 44%,
      57%, and 40%, respectively, than that of wounds treated with continuous,
      intermittent, and dynamic NPWT. Analysis of 3D images revealed a greater
      reduction in wound area and perimeter in NPWTi wounds compared to all NPWT wounds
      (P < .05). In addition, the average wound fill rate for NPWTi wounds was faster
      than that for continuous (40%; P < .05), intermittent (25%; P > .05), and dynamic
      (65%; P < .05) NPWT wounds. CONCLUSIONS: Although not confirmed in humans, these
      porcine data suggest that NPWTi with saline may stimulate a faster rate of wound
      granulation than NPWT in continuous and noncontinuous modes.

PMID- 24106565
TI  - CASE REPORT Pan-Suture Synostosis After Posterior Vault Distraction.
AB  - OBJECTIVE: Posterior vault remodeling by distraction osteogenesis is a relatively
      new technique used for initial correction of turribrachycephaly in children with
      bicoronal craniosynostosis. We present a new potential complication from this
      procedure; a case of pan-suture synostosis subsequent to posterior vault
      distraction. METHODS: We report an infant girl who presented with bicoronal
      synostosis in the setting of Saethre-Chotzen syndrome. She underwent posterior
      vault distraction and was distracted a total of 34 millimeters, with successful
      osteogenesis at the site. RESULTS: One year postoperatively, the patient was
      found to have incidental, asymptomatic pan-suture synostosis on computed
      tomography. CONCLUSIONS: To our knowledge, this is the first reported case of
      delayed craniosynostosis after posterior vault distraction in the literature. The
      possible pathogenesis and significance of this case are discussed with a review
      of the current literature.

PMID- 24106563
TI  - Total posterior leg open wound management with free anterolateral thigh flap:
      case and literature review.
AB  - Soft tissue coverage of the exposed Achilles tendon is a unique reconstructive
      challenge. In this report, we describe the management of a large posterior leg
      wound with exposed Achilles tendon using a free anterolateral thigh (ALT) flap. A
      careful review of alternative reconstructive options is included, along with
      their respective advantages and disadvantages. A 32-year-old white man suffered a
      fulminant right lower extremity soft tissue infection requiring extensive
      debridement of the entire posterior surface of the right leg. The resulting large
      soft tissue defect included exposure of the Achilles tendon. Reconstruction of
      the defect was achieved with an ALT flap and split-thickness skin graft for
      coverage of the Achilles tendon and gastrocnemius muscle, respectively. The
      patient was able to ambulate independently within 2 months of the procedure. 

PMID- 24106566
TI  - Phytophotodermatitis.

PMID- 24106567
TI  - Raynaud's Phenomenon.

PMID- 24106568
TI  - Breast reduction mammaplasty.

PMID- 24106569
TI  - [Antibiotic resistant furuncles: think myiasis].

PMID- 24106570
TI  - Cost effectiveness of using surgery versus skeletal traction in management of
      femoral shaft fractures at Thika level 5 hospital, Kenya.
AB  - INTRODUCTION: A prospective quasi experimental study was undertaken at the Thika
      level 5 hospital. The study aimed to compare the costs of managing femoral shaft
      fracture by surgery as compared to skeletal traction. METHODS: Sixty nine (46.6%)
      patients were enrolled in group A and managed surgically by intramedullary
      nailing while 79 (53.4%) patients were enrolled in group B and managed by
      skeletal traction. Exclusion criteria included patients with pathological
      fractures and previous femoral fractures. Data was collected by evaluation of
      patients in patient bills using a standardized questionnaire. The questionnaire
      included cost of haematological and radiological tests, bed fees, theatre fees
      and physiotherapy costs. The data was compiled and analyzed using SPSS version
      16. Person's chi square and odds ratios were used to measure associations and
      risk analysis respectively. RESULTS: A higher proportion of patients (88.4%) in
      group A were hospitalized for less than one month compared to 20 patients (30.4%)
      in group B (p, 0.001).Total cost of treatment in group A was significantly lower
      than in group B. Nineteen (27.9%) patients who underwent surgery paid a total
      bill of Ksh 5000-7500 compared to 7(10.4%) who were treated by traction. The
      financial cost benefit of surgery was further complimented by better functional
      outcomes. CONCLUSION: The data indicates a cost advantage of managing femoral
      shaft fracture by surgery compared to traction. Furthermore the longer hospital
      stay in the traction group is associated with more malunion, limb deformity and
      shortening.

PMID- 24106571
TI  - [Lipschutz ulcer: a rare and underdiagnosed cause of genital ulcer].

PMID- 24106572
TI  - Perceptions of the usefulness of external support to immunization coverage in
      Chad: an analysis of the GAVI-Alliance cash-based support.
AB  - INTRODUCTION: Chad is one of the countries supported by the GAVI-Alliance that
      remains with unsatisfactory vaccination coverage. This paper tries to understand
      the main barriers to better coverage. METHODS: These barriers were categorised as
      up or downstream against the health system building blocks as proposed by WHO and
      compared with barriers and activities identified by the country in its health
      system's strengthening grant proposal as approved by the GAVI Alliance in 2007.
      Data were collected using a modified Delphi system and by analysis of grant and
      annual report documents. RESULTS: Most of the activities anticipated under the
      GAVI health system's strengthening proposal are activities targeting downstream
      barriers (the neglect of upstream issues is of major importance in a
      decentralised state like Chad) and aligned with, not complementary to,
      immunization services strengthening activities. Further, both set of cash grants
      are blind to important recommendations such as the need to address barriers at
      the level of leadership and governance and at the level of the financing system
      and also about initiatives to promote community demand of vaccination services.
      CONCLUSION: IN CHAD SLOW VACCINATION PROGRESS IS AGGRAVATED BY SEVERAL CONTEXTUAL
      BARRIERS: the size of the country, the low population density, the nomadic nature
      of a significant part of its peoples, the recent civil war, associated with civil
      unrest and political instability and its geographical localization. In this
      situation it would be important to sustain downstream operations (the major focus
      of the ISS grant) while taking a long term view of the needs of the health
      system. The GAVI effectively supports downstream operations, but neglects the
      long term view.

PMID- 24106573
TI  - Serial pathologic fractures of five long bones on four separate occasions in a
      patient with primary hyperparathyroidism, challenges of management in a
      developing country: a case report.
AB  - Multiple pathologic fractures secondary to parathyroid adenoma is rarely
      recognized and reported in the tropics. Inadequate evaluation causes worsened
      disability and increased psychological stress. We present a 27-year-old Nigerian
      male student with recurrent unexplained pathological fractures of the long bones.
      Primary Hyperparathyroidism was later diagnosed and he benefited from a
      unilateral parathyroidectomy. Primary hyperparathyroidism secondary to
      parathyroid adenoma is difficult to diagnose and needs a high index of suspicion.
      Surgery and good post-operative biochemical control of serum calcium produce
      satisfying outcomes. 

PMID- 24106574
TI  - Assessment of laboratory logistics management information system practice for
      HIV/AIDS and tuberculosis laboratory commodities in selected public health
      facilities in Addis Ababa, Ethiopia.
AB  - INTRODUCTION: Logistics management information system for health commodities
      remained poorly implemented in most of developing countries. To assess the status
      of laboratory logistics management information system for HIV/AIDS and
      tuberculosis laboratory commodities in public health facilities in Addis Ababa.
      METHODS: A cross-sectional descriptive study was conducted from September 2010
      January 2011 at selected public health facilities. A stratified random sampling
      method was used to include a total of 43 facilities which, were investigated
      through quantitative methods using structured questionnaires interviews. Focus
      group discussion with the designated supply chain managers and key informant
      interviews were conducted for the qualitative method. RESULTS: There exists a
      well-designed logistics system for laboratory commodities with trained pharmacy
      personnel, distributed standard LMIS formats and established inventory control
      procedures. However, majority of laboratory professionals were not trained in
      LMIS. Majority of the facilities (60.5%) were stocked out for at least one ART
      monitoring and TB laboratory reagents and the highest stock out rate was for
      chemistry reagents. Expired ART monitoring laboratory commodities were found in
      25 (73.5%) of facilities. Fifty percent (50%) of the assessed hospitals and 54%
      of health centers were currently using stock/bin cards for all HIV/AIDS and TB
      laboratory commodities in main pharmacy store, among these only 25% and 20.8% of
      them were updated with accurate information matching with the physical count done
      at the time of visit for hospitals and health centers respectively. CONCLUSION:
      Even though there exists a well designed laboratory LMIS, keeping quality
      stock/bin cards and LMIS reports were very low. Key ART monitoring laboratory
      commodities were stock out at many facilities at the day of visit and during the
      past six months. Based on findings, training of laboratory personnel's managing
      laboratory commodities and keeping accurate inventory control procedures were
      recommended.

PMID- 24106575
TI  - [Dermal toxicity of erlotinib].

PMID- 24106576
TI  - [Subcutaneous nodule revealing an angioleiomyoma].

PMID- 24106577
TI  - [Tendinous and tuberous xanthomas revealing familial hypercholesterolemia].

PMID- 24106578
TI  - HIV self-testing practices among Health Care Workers: feasibility and options for
      accelerating HIV testing services in Ethiopia.
AB  - INTRODUCTION: HIV is still an enormous global burden and it is also causing loss
      of huge health care workers (HCWs) on the already limited human resource capacity
      in health care services in Sub-Saharan Africa. Variety of methods of accelerating
      HIV testing is required to increase the rate of HIV testing and expand treatment
      services. Therefore, this study was aimed to find out the prevalence, feasibility
      and options of HIV self-testing practices in Ethiopia. METHODS: A cross-sectional
      study design triangulated with qualitative method was conducted from February to
      May, 2012. The data was collected using a semi-structured pretested questionnaire
      and in-depth interview, at government and private health centers or clinics and
      hospitals. During the data collection all the available healthcare workers (HCWs)
      which encompass the internship students including: Medical, Health Officer,
      Nurses, Midwives and Laboratory students, and health professionals working in the
      selected health institutions were involved. RESULTS: A total of 307 HCWs were
      included in the analysis and we found that 288(94.4%) of them were ever tested
      for HIV, of which majority 203 (70.5%) were tested by themselves though 244(80%)
      of the HCWs had motivation or interest to be tested by themselves. Generally, of
      the ever tested only 85(29.5%) were tested by the help of health care
      providers/counselors other than self. Regarding the place where the HCWs had the
      test, majority 136 (69.4%) tested by themselves at the health facility and the
      rest were tested at their home, office, market and church. The main reason stated
      for self-testing was the need for confidentiality for the test result, which was
      mentioned by 205(82%). Moreover, 35(14.0%) claims lack of time to access the
      ordinary counseling and testing services. CONCLUSION: This study depicts high
      rate of HIV self-testing practice among HCWs. This shows that HIV self-testing
      can be considered as one pillar to increase the HIV-testing services and a means
      for the HIV prevention and control policy, through increasing HIV testing uptake
      and awareness of HIV status. However, the implementation may require the role of
      different stakeholders and decision makers with further study to extend the
      options.

PMID- 24106579
TI  - Fifteen years after a ferry disaster: clinical interviews and survivors' self
      assessment of their experience.
AB  - BACKGROUND: Disasters yield increased rates of psychological disorders decades
      later. Other consequences, however, have received little attention in the past.
      OBJECTIVE: We aimed to examine diagnostic status and survivors' views on disaster
      related consequences and social support. METHODS: A mixed-methods approach was
      used with 22 survivors (of 49 eligible) 15 years after a ferry disaster. Data
      collection included audiotaped interviews with open-ended questions and
      diagnostic assessment of Axis-I disorders. RESULTS: The post-disaster incidence
      was 54% (12/22) for Axis-I disorders, and 45% (10/22) for full or subsyndromal
      posttraumatic stress disorder. Thematic analysis revealed that survivor
      perception of the long-term consequences included positive (character change) and
      negative aspects (being ascribed a survivor identity). Participants' sought
      social support for several years, yet many felt hindered by experiential
      dissimilarity and distress of significant others. CONCLUSIONS: Axis-I disorders
      were prevalent, but not salient to survivors' perceptions in the long-term. Post
      disaster interventions need to attend to common barriers to support.

PMID- 24106581
TI  - Publication delay in the korean journal of family medicine.

PMID- 24106580
TI  - A novel radial water tread maze tracks age-related cognitive decline in mice.
AB  - There is currently no treatment and cure for age-related dementia and cognitive
      impairment in humans. Mice suffer from age-related cognitive decline just as
      people do, but assessment is challenging because of cumbersome and at times
      stressful performance tasks. We developed a novel radial water tread (RWT) maze
      and tested male C57BL/6 (B6) and C57BL/6 x Balb/c F1 (CB6F1) mice at ages 4, 12,
      20, and 28 months. B6 mice showed a consistent learning experience and memory
      retention that gradually decreased with age. CB6F1 mice showed a moderate
      learning experience in the 4 and 12 month groups, which was not evident in the 20
      and 28 month groups. In conclusion, CB6F1 mice showed more severe age-related
      cognitive impairment compared to B6 mice and might be a suitable model for
      intervention studies. In addition, the RWT maze has a number of operational
      advantages compared to currently accepted tasks and can be used to assess age
      related cognition impairment in B6 and CB6F1 mice as early as 12 months of age. 

PMID- 24106582
TI  - Postmarketing surveillance study of the efficacy and safety of phentermine in
      patients with obesity.
AB  - BACKGROUND: Obesity is a complex problem that is now considered a chronic
      metabolic disease. In Korea, phentermine has been widely used for the treatment
      of obesity in the primary care setting since 2004. However, there have been very
      few studies on the safety and efficacy of phentermine. To investigate the safety
      and efficacy of this drug, a postmarketing surveillance study was performed.
      METHODS: A total of 795 patients with obesity (body mass index >= 25 kg/m(2))
      were enrolled from 30 primary care centers in Korea from September 2006 to
      November 2007. Patients were examined to ascertain safety and efficacy at 4-, 8-,
      and 12-week intervals. The criterion for efficacy was defined as a weight loss >=
      5% of body weight. RESULTS: Of the 795 enrolled patients, 735 (92.5%) were
      evaluated in safety assessments and 711 (89.4%) was included in efficacy
      assessments. A total of 266 adverse events (AEs) were reported by 218 patients
      (30.6%), and no serious AEs were reported. Among 711 patients, 324 patients
      (45.6%) lost >= 5% of their body weight. The mean weight loss was 3.8 +/- 4.0 kg.
      CONCLUSION: AEs are commonly associated with phentermine, even though phentermine
      is effective for weight loss and relatively well-tolerated.

PMID- 24106583
TI  - The cutoff value of waist circumference for predicting metabolic risks in pre-
      and post-menopausal korean women: analysis of 2010 korean national health and
      nutrition examination survey data.
AB  - BACKGROUND: With metabolic syndrome (MS) being a major risk factor for
      cardiovascular disease, and central obesity being a major predisposing factor for
      MS, intensive research is currently being performed on cutoff values according to
      race and sex. Menopause is an especially significant factor in designating cutoff
      values for female central obesity, as menopause brings sudden bodily changes that
      induce central obesity and increased prevalence of MS. Therefore this study aimed
      to investigate the cutoff values for the obesity index and its validity in
      predicting the criteria for MS in Korean women according to menstrual status.
      METHODS: The study focused on 3,103 women 20 years of age or older participating
      in the 2007 Korea National Health and Nutrition Examination Survey. Definitions
      of non-adipose components of MS were defined by the International Diabetes
      Federation, and menstrual status was judged on the basis of survey results. The
      sensitivity, specificity, and positive and negative predictive values of the
      central obesity index (body mass index [BMI], waist circumference [WC], waist-to
      height ratio [WHtR]) according to menstrual status for two or more non-adipose
      components of MS were calculated based on the Youden index. RESULTS: Area under
      the curve (AUC) values predicting the presence of two or more metabolic risk
      factors were higher in pre-menopausal women, with AUC values for BMI, WC, and
      WHtR being, in pre- and post-menopausal women, 23.1 kg/m(2) vs. 23.9 kg/m(2),
      76.1 cm vs. 82.5 cm, and 0.49 vs. 0.53, respectively. The WC cut off (76 cm) for
      pre-menopausal women was found to be more sensitive and more effective at
      screening for MS risks than the cutoff value given by the Korea Society for the
      Study of Obesity. CONCLUSION: The central obesity index showed better
      predictability for MS risk in pre-menopausal women. Because the central obesity
      index cutoff values are lower in pre-menopausal women, the possibility of
      metabolic risk can be considered for pre-menopausal women with WC lower than 85
      cm. Assessment and control of other risks are needed accordingly for preventing
      the development of MS.

PMID- 24106584
TI  - Survey of Potentially Inappropriate Prescription Using STOPP/START Criteria in
      Inha University Hospital.
AB  - BACKGROUND: Prescribing potentially harmful drugs and omitting essential drugs to
      older patients is a common problem because they take so many medications. In this
      study, our goal was to identify potentially inappropriate medications (PIMs) and
      potential prescribing omissions (PPOs) using Screening Tool of Older Persons'
      potentially inappropriate Prescriptions (STOPP) and Screening Tool to Alert
      doctors to the Right Treatment (START) criteria to improve proper prescription
      and reduce improper prescription. METHODS: Enrolled in this study were 117
      patients older than 65 years old who were hospitalized at Inha University
      Hospital in Incheon due to pneumonia from January 2012 to March 2012. Patient
      data, including medical histories, current diagnoses, current medications, and
      biochemical data were recorded from electronic records. STOPP and START were
      applied to their clinical datasheets. RESULTS: STOPP criteria identified 24
      patients who had 29 PIMs. Most potential inappropriate prescribing was of
      cardiovascular medications, followed by drugs whose primary effect is on the
      urogenital system and gastrointestinal system. START criteria identified 31
      patients who had 46 PPOs. The cardiovascular system drugs comprised most of the
      PPOs. No PPOs were identified under the central nervous system criteria.
      CONCLUSION: Given the current Korean medical system conditions and considering
      the many clinically important situations when prescribing drugs, STOPP/START
      criteria are not absolute criteria to prevent improper prescription, but
      sagacious usage of these standards can help physicians to prescribe properly in
      clinical practice.

PMID- 24106585
TI  - Predictability of various serial subtractions on global deterioration scale
      according to education level.
AB  - BACKGROUND: The serial 100-7s subtraction, an item on the Mini-Mental State
      Examination (MMSE), is well known for being difficult for uneducated people.
      Therefore, we investigated into alternative serial subtractions for serial 100-7s
      subtraction in uneducated people. METHODS: One hundred sixty-nine subjects were
      enrolled by neurologic or neuropsychiatric out-patient clinics in 4 university
      medical centers. The subjects were divided into two groups: an uneducated group
      and an educated group (at least primary schooling) by questionnaire. We
      investigated the correlation between incorrect number of serial subtractions and
      Global Deterioration Scale (GDS) score in both groups and undertook receiver
      operating characteristic (ROC) curve analysis. MMSE including serial 40-4s
      subtraction, serial 20-2s subtraction, and serial 10-1s subtraction instead of
      serial 100-7s subtraction were arbitrally named MMSE4, MMSE2, and MMSE1. RESULTS:
      In the educated group, serial 100-7s subtraction showed the highest correlation
      with GDS score (correlation coefficient, 0.465; P < 0.001). In the uneducated
      group, serial 40-4s subtraction showed the highest correlation with GDS score
      (correlation coefficient, 0.608; P < 0.001), and serial 100-7s indicated the
      lowest correlation (correlation coefficient, 0.378; P = 0.023). In ROC curve
      analysis for MMSE, MMSE4, MMSE2, and MMSE1 to assess the presence of dementia
      (GDS score >= 3) in uneducated subjects, the area under the curve (AUC) was
      0.648, 0.770, 0.758, and 0.711, respectively, and in educated subjects, AUC for
      MMSE, MMSE4, MMSE2, and MMSE1 was 0.729, 0.719, 0.716, and 0.714, respectively.
      CONCLUSION: Out of MMSE items, serial 100-7s is adequate in the educated elderly,
      but may be less adequate in the uneducated elderly. Serial 40-4s seems to be more
      appropriate for MMSE in the uneducated elderly.

PMID- 24106586
TI  - Relationships between Dietary Habits and Allostatic Load Index in Metabolic
      Syndrome Patients.
AB  - BACKGROUND: Allostatic load (AL) measures overall physiological wear and tear on
      one's body, as a preclinical marker of pathophysiologic processes that precede
      the onset of disease. We studied the association of dietary habits with AL.
      METHODS: Consecutive patients visiting a tertiary hospital Health Promotion
      Center from September 2009 to February 2010, older than 20 years with metabolic
      syndrome were selected for study (n = 204). By multivariable linear regression
      analysis, we investigated the association of various dietary habits evaluated by
      questionnaires. RESULTS: In male, multivariable linear regression showed a
      significant negative association between fat preference and AL with BMI >= 30
      (1st quartile [Q] vs. 2Q: beta = -3.71; 95% confidence interval [CI], -6.26 to 
      1.16), a significant negative association between salt preference and AL with BMI
      25-30 (beta = -1.36; 95% CI, -2.46 to -0.26), a negative association between
      appetite control and AL with BMI < 25 (1Q vs. 3Q: beta = -1.54; 95% CI, -3.00 to 
      0.096), a significant positive association between appetite control and AL with
      BMI 25-30 (1Q vs. 3Q: beta = 1.30; 95% CI, 0.12 to 2.48), and a significant
      positive association between eating in response to food cues and AL in males with
      BMI 25-30 (1Q vs. 4Q: beta = 1.09; 95% CI, 0.020 to 2.15). CONCLUSION: Our
      results suggest that metabolic syndrome patients should be discouraged from
      eating fat and eating in response to food cues, and should be educated about
      nutrition and balanced diet.

PMID- 24106587
TI  - The Association between Pain and Depression, Anxiety, and Cognitive Function
      among Advanced Cancer Patients in the Hospice Ward.
AB  - BACKGROUND: Pain is the most common but severe physical symptom among cancer
      patients. This study aimed to identify correlation between pain and psychological
      symptoms for terminal cancer patients. METHODS: The total sample consisted of 69
      subjects who were recruited through two hospice wards, limited to patients who
      were mentally alert and had no psychiatric diseases. The subjects were divided
      into two groups according to the numerical rating scale: the pain-free group, 0
      to 3 points; and the pain group, 4 to 10 points. We used the Beck depression
      inventory (BDI), Beck anxiety inventory (BAI), mini-mental status examination
      Korea (MMSE-K), and short form 36 health survey (SF-36). Logistic regression
      analysis was performed to verify the correlation between pain and other
      psychosocial disorders. RESULTS: The mean scores of BDI in the pain-free and pain
      groups were 25.7 and 31.5; mean BAI scores were 23.4 and 34.7; mean MMSE-K scores
      were 25.7 and 21.8, respectively. There were no significant differences between
      the two groups in SF-36 score except scores of body pain. The results of logistic
      regression analysis adjusted for age, sex, marital status, types of cancer,
      history of chemotherapy, or radiotherapy showed significant correlation between
      pain and depression (BDI >= 24; odds ratio [OR], 4.199; 95% confidence interval
      [CI], 1.171 to 15.060), and pain and cognitive impairment (MMSE < 24; OR, 5.495;
      95% CI, 1.449 to 20.843); but not between pain and anxiety (BAI >= 22; OR, 3.011;
      95% CI, 0.907 to 9.997). CONCLUSION: Pain significantly affects depression and
      cognitive impairment among advanced cancer patients in the hospice ward.
      Accordingly, more aggressive treatment of pain is required to reduce not only
      physical suffering but also physiological distress.

PMID- 24106588
TI  - Satisfaction and difficulties of korean family medicine resident training
      faculty.
AB  - BACKGROUND: Practitioners of family medicine are essential to primary care
      practices in Korea. Resident training staffs in Korean family medicine
      departments have a crucial role in producing well-trained family physicians. This
      study assesses the aspects of satisfaction and difficulties of Korean family
      medicine resident training staffs. METHODS: We surveyed the resident training
      staffs of various Korean family medicine departments using an online survey tool.
      The survey used in this study was modified from previously used questionnaires.
      Respondents rated items using a five-point Likert scale and a 0-10 visual
      analogue scale. RESULTS: The response rate was 43.9% (122/278). The mean
      satisfaction score with regard to current family medicine residency programs was
      7.59 out of 10. Resident training staffs found the administrative aspects of
      their role to be the most difficult. There were considerable differences in the
      reported difficulties of resident training according to the differing
      characteristics of each staff member, including age, sex, type of hospital,
      number of staff members, role as chief, and duration of staff. Most respondents
      (91.9%) cited a need for faculty development programs. CONCLUSION: Korean family
      medicine resident training staffs need faculty development programs for the
      improvement of resident training. For the strengthening of core competencies
      among resident training staffs, faculty development programs or courses should be
      designed and implemented in Korea.

PMID- 24106589
TI  - Pyogenic liver abscess following acupuncture and moxibustion treatment.
AB  - Acupuncture treatment is generally regarded as a relatively safe procedure.
      However, most procedures have some complications and acupuncture treatment is no
      exception. Reported complications of acupuncture treatment were mostly mild or
      temporary symptoms, but certain severe adverse effects were also observed. We
      report here for the first time a case of liver abscess following acupuncture and
      moxibustion treatment. 

PMID- 24106590
TI  - Comments on statistical issues in september 2013.

PMID- 24106591
TI  - Human Papillomavirus Type16- L1 VLP Production in Insect Cells.
AB  - OBJECTIVE(S): Infection by high-risk papillomavirus is regarded as the major risk
      factor in the development of cervical cancer. Recombinant DNA technology allows
      expression of the L1 major capsid protein of HPV in different expression systems,
      which has intrinsic capacity to self-assemble into viral-like particles (VLP).
      VLPS are non-infectious, highly immunogenic and can elicit neutralizing
      antibodies. VLP-based HPV vaccines can prevent persistent HPV infections and
      cervical cancer. In this study recombinant HPV-16 L1 protein was produced in Sf9
      insect cells and VLP formation was confirmed. MATERIALS AND METHODS: Complete HPV
      16 L1 gene was inserted into pFast HTa plasmid and transformed into DH10BAC
      Escherichia coli containing bacmid and helper plasmid. The recombinant Bacmid
      colonies turned to white and non-recombinant colonies harboring L1 gene remained
      blue in the presence of X-gal and IPTG in colony selection strategy. To confirm
      the recombinant bacmid production, PCR was applied using specific L1 primers. To
      produce recombinant baculovirus, the recombinant bacmid DNA was extracted and
      transfected into Sf9 cells using Cellfectin. The expression of L1 in Sf9 cells
      was identified through SDS-PAGE and western blot analysis using specific L1
      monoclonal antibody. Self-assembled HPV16L-VLPs in Sf9 cells was confirmed by
      electron microscopy. RESULTS: The recombinant protein L1 was predominantly ~60 KD
      in SDS-PAGE with distinct immunoreactivity in western blot analysis and formed
      VLPS as confirmed by electron microscopy. CONCLUSION: Application of recombinant
      baculovirus containing HPV-16 L1 gene will certainly prove to be a constructive
      tool in production of VLPs for prophylactic vaccine development as well as
      diagnostic tests.

PMID- 24106592
TI  - Effect of Methylsulfonylmethane Pretreatment on Aceta-minophen Induced
      Hepatotoxicity in Rats.
AB  - OBJECTIVE(S): Methylsulfonylmethane (MSM) is a sulfur-containing compound found
      in a wide range of human foods including fruits, vegetables, grains and
      beverages. In this study the effect of MSM pretreatment on acetaminophen induced
      liver damage was investigated. MATERIALS AND METHODS: Male Sprague Dawley rats
      were pretreated with 100 mg/kg MSM for one week. On day seven rats were received
      acetaminophen (850 mg/kg, intraperitoneal). Twenty-four hours later, blood
      samples were taken to determine serum aspartate aminotransferase (AST) and
      alanine aminotransferase (ALT). Tissue samples of liver were also taken for the
      determination of the levels of malondialdehyde (MDA); total glutathione (GSH),
      superoxide dismutase (SOD), and myeloperoxidase (MPO) activity together with
      histopathological observations. RESULTS: High dose of acetaminophen
      administration caused a significant decrease in the GSH level of the liver
      tissue, which was accompanied with a decrease in SOD activity and increases in
      tissue MDA level and MPO activity. Serum ALT, AST levels were also found elevated
      in the acetaminophen-treated group. Pretreatment with MSM for one week was
      significantly attenuated all of these biochemical indices. CONCLUSION: Our
      findings suggest that MSM pretreatment could alleviate hepatic injury induced by
      acetaminophen intoxication, may be through its sulfur donating and antioxidant
      effects.

PMID- 24106593
TI  - Using eggshell membrane as nerve guide channels in peripheral nerve regeneration.
AB  - OBJECTIVE(S): The aim of this study was to evaluate the final outcome of nerve
      regeneration across the eggsell membrane (ESM) tube conduit in comparison with
      autograft. MATERIALS AND METHODS: Thirty adult male rats (250-300 g) were
      randomized into (1) ESM conduit, (2) autograft, and (3) sham surgery groups. The
      eggs submerged in 5% acetic acid. The decalcifying membranes were cut into four
      pieces, rotated over the teflon mandrel and dried at 37( degrees )C. The left
      sciatic nerve was surgically cut. A 10-mm nerve segment was cut and removed. In
      the ESM group, the proximal and distal cut ends of the sciatic nerve were
      telescoped into the nerve guides. In the autograft group, the 10 mm nerve segment
      was reversed and used as an autologous nerve graft. All animals were evaluated by
      sciatic functional index (SFI) and electrophysiology testing. RESULTS: The
      improvement in SFI from the first to the last evalution in ESM and autograft
      groups were evaluated. On days 49 and 60 post-operation, the mean SFI of ESM
      group was significantly greater than the autograft group (P< 0.05). On day 90,
      the mean nerve conduction velocity (NCV) of ESM group was greater than autograft
      group, although the difference was not statistically significant (P> 0.05).
      CONCLUSION: These findings demonstrate that ESM effectively enhances nerve
      regeneration and promotes functional recovery in injured sciatic nerve of rat.

PMID- 24106594
TI  - Effect of Melatonin on the Expression of Apoptotic Genes in Vitrified-thawed
      Spermatogonia Stem Cells Type A of 6-Day-Old Mice.
AB  - OBJECTIVE(S): Being secreted by the pineal gland, melatonin induces cell
      proliferation in normal cells and induced apoptosis in cancer cells. The purpose
      of this study was to investigate effects of melatonin on main components and the
      expression of apoptotic genes in vitrified-thawed testicular germ cells of 6- day
      old mice. MATERIALS AND METHODS: Testes of neonate Balb/c mice were vitrified-
      thawed under standard condition with or without the addition of 100 MUM melatonin
      to both vitrification and thawing solutions. Subsequently, Vitrified-thawed whole
      testes were digested under standard condition and spermatogonial stem cells type
      A were separate in the suspension with CD90.1 (Thy1.1(+)) micro beads. Extraction
      of RNA and synthesis of cDNA was performed. Expression levels of apoptotic genes
      (Fas, P53, BCL-2 and BAX) were determined using Real-time PCR. Results : With all
      genes being expressed, level of expression for Fas was higher and for that of P
      53 was lower than the remaining genes. Conclusion : Melatonin may cause apoptosis
      in cells being damaged under the influence of freezing thawing process. In order
      to examine the exact effects of melatonin on spermatogonia stem cells apoptosis,
      additional studies are required.

PMID- 24106595
TI  - Quantitative Structure-Activity Relationship Studies of 4-Imidazolyl- 1,4
      dihydropyridines as Calcium Channel Blockers.
AB  - OBJECTIVE(S): The structure- activity relationship of a series of 36 molecules,
      showing L-type calcium channel blocking was studied using a QSAR (quantitative
      structure-activity relationship) method. MATERIALS AND METHODS: Structures were
      optimized by the semi-empirical AM1 quantum-chemical method which was also used
      to find structure-calcium channel blocking activity trends. Several types of
      descriptors, including electrotopological, structural and thermodynamics were
      used to derive a quantitative relationship between L-type calcium channel
      blocking activity and structural properties. The developed QSAR model contributed
      to a mechanistic understanding of the investigated biological effects. RESULTS:
      Multiple linear regressions (MLR) was employed to model the relationships between
      molecular descriptors and biological activities of molecules using stepwise
      method and genetic algorithm as variable selection tools. The accuracy of the
      proposed MLR model was illustrated using cross-validation, and Y-randomisation 
      as the evaluation techniques. CONCLUSION: The predictive ability of the model was
      found to be satisfactory and could be used for designing a similar group of 1,4-
      dihydropyridines , based on a pyridine structure core which can block calcium
      channels.

PMID- 24106596
TI  - Analysis of CFTR Gene Mutations in Children with Cystic Fibrosis, First Report
      from North-East of Iran.
AB  - OBJECTIVE(S): More than 1500 registered mutations in cystic fibrosis
      transmembrane regulator (CFTR) gene are responsible for dysfunction of an ion
      channel protein and a wide spectrum of clinical manifestations in patients with
      cystic fibrosis (CF). This study was performed to investigate the frequency of a
      number of well-known CFTR mutations in North Eastern Iranian CF patients.
      MATERIAL AND METHODS: A total number of 56 documented CF patients participated in
      this study. Peripheral blood was obtained and DNA extraction was done by the use
      of routin methods. Three steps were taken for determining the target mutations:
      ARMS-PCR was performed for common CFTR mutations based on previous reports in
      Iran and neighboring countries. PCR-RFLP was done for detection of R344W and
      R347P, and PCR-Sequencing was performed for exon 11 in patients with unidentified
      mutation throughout previous steps. Samples which remained still unknown for a
      CFTR mutation were sequenced for exon 12. RESULTS: Among 112 alleles, 24 mutated
      alleles (21.42%) were detected: DeltaF508 (10.71%), 1677delTA (3.57%), S466X
      (3.57%), N1303K (0.89%), G542X (0.89%), R344W (0.89%), L467F (0.89%). Eight out
      of 56 individuals analyzed, were confirmed as homozygous and eight samples showed
      heterozygous status. No mutations were detected in exon 12 of sequenced samples.
      CONCLUSION: Current findings suggest a selected package of CFTR mutations for
      prenatal, neonatal and carrier screening along with diagnosis and genetic
      counseling programs in CF patients of Khorasan.

PMID- 24106597
TI  - Pentoxifylline Protects the Rat Liver Against Fibrosis and Apoptosis Induced by
      Acute Administration of 3,4-Methylenedioxymethamphetamine (MDMA or Ecstasy).
AB  - OBJECTIVE(S): 3,4-Methylenedioxymethamphetamine (MDMA) is one of the most popular
      drugs of abuse in the world with hallucinogenic properties that has been shown to
      induce apoptosis in liver cells. The present study aimed to investigate the
      effects of pentoxifylline (PTX) on liver damage induced by acute administration
      of MDMA in Wistar rat. MATERIALS AND METHODS: Animals were administered with
      saline or MDMA (7.5 mg/kg, IP) 3 times with 2 hr intervals. PTX (200 mg kg, IP),
      was administered simultaneously with last injection of MDMA in experimental
      group. RESULTS: The concomitant administration of pentoxifylline and MDMA
      decreased liver injury including apoptosis, fibrosis and hepatocytes damages.
      CONCLUSION: Our results showed for the first time that PTX treatment diminishes
      the extent of apoptosis and fibrosis caused by MDMA in rat liver.

PMID- 24106598
TI  - Interplay of Phosphorylated Apoptosis Repressor with CARD, Casein Kinase-2 and
      Reactive Oxygen Species in Regulating Endothelin-1-Induced Cardiomyocyte
      Hypertrophy.
AB  - OBJECTIVE(S): The role of the Apoptosis repressor with caspase recruitment domain
      (ARC) in apoptosis and in certain hypertrophic responses has been previously
      investigated, but its regulation of Endothelin-1 induced cardiac hypertrophy
      remains unknown. The present study discusses the inhibitory role of ARC against
      endothelin-induced hypertrophy. RESULTS: In present study Endothelin treated
      cardiomyocytes were used as a hypertrophic model, that were subsequently treated
      with adenovirus ARC and its mutant at different multiplicity of infections.
      Casein-kinase-2 inhibitors were used to produce dephosphorylated ARC and to study
      its effect on hypertrophy. Hypertrophy was assessed by cell surface area
      measurement, Atrial-natriuretic-Factor mRNA analysis and total protein assay.
      Reactive oxygen species analysis was carried out using the dichlorofluorescin
      diacetate (DCFH-DA) assay. Over expression of ARC significantly inhibits
      Endothelin-induced cardiomyocyte hypertrophy. The nonphosphorylated mutant ARC
      (T149 A) remained unable to control endothelin-induced hypertrophy, suggesting a
      vital role for ARC phosphorylation in regulation of its activity. Sensitization
      study has been carried out to check the role of endogenous ARC using casein
      kinase inhibitors. Finally, the significant role of ARC in regulating reactive
      oxygen species -mediated control of endothelin induced hypertrophy has also been
      assessed. Conclusion : Conclusively, present study showed the vital and potential
      therapeutic interventional role of ARC in preventing endothelin-1-induced
      cardiomyocyte hypertrophy. The regulation of hypertrophic pathway by ARC relies
      on blunting the reactive oxygen species attack. This study further suggests a
      mediatory role of casein-kinase-2 in Endothelin-induced hypertrophy, mainly
      through its phosphorylation of ARC.

PMID- 24106599
TI  - T lymphocyte apoptosis in systemic lupus erythematosus patients.
AB  - OBJECTIVE(S): Apoptosis is a tightly regulated process and plays a crucial role
      in autoimmune diseases. Because abnormalities in apoptosis are considered to be
      involved in the pathogenesis of systemic lupus erythematosus (SLE), in present
      study we studied the apoptosis in T lymphocytes from Iranian SLE patients at
      protein and gene expression levels for some molecules which are involved in
      apoptosis pathways. MATERIALS AND METHODS: Thirty five SLE patients (23 female,
      12 male), and 20 age matched controls (10 female, 10 male) participated in this
      study. T lymphocytes were isolated from peripheral blood mononuclear cells
      (PBMCs) using MACS method. Apoptosis rate was studied at protein level by flow
      cytometer using Annexin V, and at gene expression level using semi-quantitative
      RT-PCR method for detection of Fas, FasL, Bcl-2, caspase 8, and caspase 9 genes.
      RESULTS: The percentage of apoptotic cells in SLE patients was not different in
      comparison with controls (20.2% +/- 1.4 vs 21.1% +/- 1.0), but the expression
      levels of FasL, caspase 8, and caspase 9 genes in all SLE patients and in female
      patients were significantly lower than controls; 0.45R vs 0.78R for FasL, 0.74R
      vs 1.0R for caspase 8, and 0.76R vs 1.26R for caspase 9 in all SLE patients and
      0.37R vs 0.82R for FasL, 0.45R vs 1.6R for caspase 8, and 0.63R vs 1.56R for
      caspase 9 in female patients. CONCLUSION: The expression levels of FasL, caspase
      8 and caspase 9 molecules involved in apoptosis decreased in female, but not in
      male SLE patients.

PMID- 24106600
TI  - Ghrelin Does not Alter Aortic Intima-Media Thickness and Adipose Tissue
      Characteristics in Control and Obese Mice.
AB  - OBJECTIVE(S): Atherosclerosis is a chronic immune-inflammatory disease that
      generally leads to ischemic heart disease. Ghrelin has several modulatory effects
      on cardiovascular system. In this study, we investigated the effect of ghrelin on
      aortic intima-media thickness, size and the number of adipocyte cells in obese
      and control mice. MATERIALS AND METHODS: This study was conducted on 24 male
      C57BL/6 mice. The animals were divided into four groups: control, obese (received
      high fat diet), control+ghrelin (injected with 100 ug/Kg subcutaneously, bid) and
      obese+ghrelin (n=6 each). After 10 days, animals were sacrificed and epididymal
      adipose tissue and thoracic aortae were removed. Adipocyte cell number, size and
      aortic intima-media thickness were evaluated. RESULTS: Ghrelin did not change
      adipocyte cell number and size and aortic intima-media thickness in obese and
      control mice. In this study, high fat diet significantly decreased the number of
      adipocyte cells while increased their size (P<0.05). Ghrelin administration had
      no significant effect on adipocyte cell number and size in obese and control
      groups (P >0.05). In addition, it could not alter aortic intima-media thickness
      in both groups. CONCLUSION: Although ghrelin has several cardiovascular effects,
      it seems that it could not alter the size and number of adipocyte cells and
      aortic intima-media thickness in diet-induced obese mice.

PMID- 24106601
TI  - DNA Sequence Fragment Containing C to A Mutation as a Convenient Mutation
      Standard for DHPLC Analysis.
AB  - OBJECTIVE(S): Denaturing high performance liquid chromatography (DHPLC) is a high
      throughput approach for screening DNA sequence variations. To assess oven
      calibration, cartridge performance, buffer composition and stability, the WAVE
      Low and High Range Mutation Standards are employed to ensure reproducibility and
      accuracy of the chromatographic analysis. The purpose of this study was to
      provide a cost-effective homemade mutation standard for DHPLC analysis. MATERIALS
      AND METHODS: DHPLC was performed to evaluate different elution temperatures of a
      374 bp DNA fragment with C>A mutation at position of 59 to achieve a peak profile
      similar to the Low Mutation Standard. In order to verify the reproducibility of
      the homemade mutation standard using DHPLC, 15 different experiments were
      performed to compare the homemade mutation standard, the WAVE Low Range Mutation
      Standard with a positive DNA control sample. RESULTS: We identified a comparable
      elution temperature and a peak profile with the WAVE Low Range Mutation Standard.
      CONCLUSION: This study confirmed the reproducibility of the peak profile of our
      homemade mutation standard compared to the Low Mutation Standard using DHPLC
      analysis.

PMID- 24106602
TI  - Lack of Association between the MEF2A Gene and Coronary Artery Disease in Iranian
      Families.
AB  - OBJECTIVE(S): Coronary artery disease (CAD) which may lead to myocardial
      infarction (MI) is a complex one. Great effort has been devoted to identification
      of genes that increase susceptibility to CAD or provide protection. A 21-bp
      deletion in the MEF2A gene, which encodes a member of the myocyte enhancer factor
      2 family of transcription factors, has been reported in patients of a single
      pedigree that exhibited autosomal-dominant inheritance of CAD. Subsequent
      analysis of genetic variants within the gene in CAD and MI case-control settings
      produced inconsistent results. Here, we aimed at assessing the contribution of
      MEF2A to CAD in a cohort of Iranian CAD patients. MATERIALS AND METHODS: Exon 11
      of MEF2A wherein the above mentioned 21-bp deletion and a polyglutamine (CAG)n
      polymorphism are positioned was sequenced by the dideoxy-nucleotide termination
      protocol. In 52 CAD patients from 12 families (3-7 affected members per family)
      and 76 Iranian control individuals. All exons of the gene were sequenced in 10
      patients and 10 controls. RESULTS: The 21-bp deletion was observed neither among
      the patients nor the control individuals. Four alleles of the polyglutamine
      (CAG)n polymorphism were found, but there were no significant differences in
      allelic frequencies between patients and controls. Sequencing of all exons of
      MEF2A revealed the presence of 12 novel sequence variations in introns and
      flanking regions of MEF2A gene, not associated with disease status. CONCLUSION:
      Our data do not support a role for MEF2A in coronary artery disease in the
      Iranian patients studied.

PMID- 24106603
TI  - Screening of Hepatitis G and Epstein-Barr Viruses Among Voluntary non Remunerated
      Blood Donors (VNRBD) in Burkina Faso, West Africa.
AB  - In most sub-Saharan countries screening of blood-transmitted infections includes
      mainly HIV, HBV, HCV and syphilis. Many viruses such as Hepatitis G (HGV) and
      Epstein-Barr virus (EBV) which also carry a risk of transmission by blood
      transfusion raise the question of the extent of screening for these pathogens.
      This work aims to evaluate the prevalence of HGV and EBV in first-time blood
      donors in Ouagadougou. The prevalence of HGV and EBV in 551 blood donors was 7.4%
      and 5.4% respectively. HGV prevalence was significantly higher in blood donors
      with hepatitis B antigens and positive for HCV compared to donors negative for
      HCV and no hepatitis B antigens (respectively p<0.001 and p=0.004). EBV
      prevalence was higher among blood donors of < 20 years age group. HBV and HCV
      positive individuals are not eligible for blood donation. This study shows
      significant results with regard to the prevalence of HGV and EBV prevalence in
      blood donors in Burkina Faso and emphasizes the need for a general screening. 

PMID- 24106604
TI  - Monocyte adhesion molecules expression in patients with chronic hepatitis C liver
      disease.
AB  - BACKGROUND: Chronic viral hepatitis is histologically characterized by
      predominantly periportal infiltration of mononuclear cells, including lymphocytes
      and monocytes/macrophages. Intralobular infiltration of these inflammatory cells
      is an ominous sign of deterioration and a criterion for disease activity.
      OBJECTIVE: To assess the monocyte inflammatory milieu, monocytes adhesion
      molecules, their endothelial receptors, cytokines and chemokines in patients with
      HCV induced chronic liver disease, in an attempt to clarify the role of blood
      monocytes in induction of inflammation and fibrogenesis in chronic hepatitis C
      liver disease. SUBJECTS AND METHODS: The current study included 60 patients with
      chronic liver disease categorized into 2groups: Patients chronic hepatitis C
      (CHC) and patients with liver cirrhosis (LC), 15 patients each; 15 healthy
      subjects were included as normal controls. Immunophenotype characterization was
      carried out by flowcytometric analysis for identification of CD11a, CD11b and
      CD49d monocyte surface antigen expression in different groups studied. The
      circulating levels of the soluble adhesion molecules (sE-selectin, sICAM-1 and
      sVCAM-1), cytokines (TNF-alpha and IL-1) and chemokines (MCP-1) were also
      assessed by immunoassays. RESULTS: Data demonstrated a significant increase
      (p<0.01) in the surface expression of CD11a on peripheral blood monocytes and in
      the circulating levels sE-selectins, sICAM-1, sVCAM-1 and TNF-alpha in both
      groups of patients compared to healthy subjects. Data also revealed a significant
      increase (p<0.01) in the surface expression of each of CD11b and CD49d on
      peripheral blood monocytes and in the circulating levels sICAM-1, sVCAM-1 and TNF
      alpha in patients with LC compared to those with CHC. Moreover, data demonstrated
      that the increase in surface antigen expression of each CD11a (p<0.01), CD11b
      (p<0.05) and CD49d (p<0.01) on circulating peripheral blood monocytes is
      positively correlated with the increase in the circulating levels of each of
      sICAM-1 and sVCAM-1 in the both groups of patients. CONCLUSIONS: These findings
      suggest that the modulation of monocyte-subset recruitment into the liver via
      adhesion molecules or cytokines/cytokine receptors may represent promising
      approaches for therapeutic interventions in human liver fibrosis. Measurement of
      serum soluble adhesion molecules may be useful for monitoring progression of
      liver inflammation and fibrosis during CHC.

PMID- 24106605
TI  - Beta-globin Gene Mutations in Turkish Children with Beta-Thalassemia: Results
      from a Single Center Study.
AB  - INTRODUCTION: The beta thalassemias are common genetic disorders in Turkey and in
      this retrospective study our aim was to evaluate beta-globin chain mutations and
      the phenotypic severity of beta-thalassemia patients followed-up in our hospital,
      a tertiary center which serves patients from all regions of Turkey. MATERIALS AND
      METHODS: 106 pediatric patients were analysed for beta-globin gene mutations by
      using DNA analysis. Patients were classified as having beta-thalassemia major or
      beta-thalassemia intermedia based on age at diagnosis, transfusion frequency and
      lowest hemoglobin concentration in between transfusions. RESULTS: There were 106
      patients (52.8% female and 47.2% male) with a mean age of 11.2+/-5 years (1.6 -
      22.3 years). Eighty-four (79.2%) patients had beta-thalassemia major, whereas the
      remaining 22 patients (20.8%) were identified as having beta-thalassemia
      intermedia. Overall, 18 different mutations were detected on 212 alleles. The
      most frequently encountered mutation was IVS I.110 (G>A) (35.3%), followed by
      Codon 8 del-AA (10.4%), IVS II.1 (G>A) (8%), IVS I.1 (G>A) (7.5%), Codon 39 (C>T)
      (7.1%) and Codon 5 (-CT) (6.6%), which made up 79.4% of observed mutations.
      According to present results, IVS I.110 (G>AA) was the most frequent mutation
      observed in this study, as in other results from Turkey. Evaluation of beta
      thalassemia mutations in 106 patients with 212 alleles, revealed the presence of
      homozygous mutation in 85 patients (80.2%) and compound heterozygous mutation in
      21 patients (19.8%). The mutations detected in patients with homozygous mutation
      were IVS I.110 (G>A) (38.8%), Codon 8 del -AA (11.8%), IVS II.1 (G>A) (8.2%) and
      IVS I.1 (G>A) (8.2%). Observed mutations in the compound heterozygotes were Codon
      39 (C>T)/Codon 41-42 (-CTTT) (14.3%), IVS I.110 (G>A)/Codon 39(C>T) (14.3%), IVS
      I.110 (G>A)/Codon 44(-C) (14.3%), and IVS II.745 (C>G)/5'UTR + 22 (G>A) (9.5%).
      CONCLUSION: Our hospital is a tertiary referral center that provides care to
      patients from all over the country, and thus the distribution of mutations
      observed in the current study is significant in term of representing that of the
      country as a whole.

PMID- 24106606
TI  - Bacterial profile, antibiotic sensitivity and resistance of lower respiratory
      tract infections in upper egypt.
AB  - BACKGROUND: Lower respiratory tract infections (LRTI) account for a considerable
      proportion of morbidity and antibiotic use. We aimed to identify the causative
      bacteria, antibiotic sensitivity and resistance of hospitalized adult patients
      due to LRTI in Upper Egypt. METHODS: A multicentre prospective study was
      performed at 3 University Hospitals for 3 years. Samples included sputum or
      bronchoalveolar lavage (BAL) for staining and culture, and serum for serology.
      Samples were cultured on 3 bacteriological media (Nutrient, Chocolate,
      MacConkey's agars). Colonies were identified via MicroScan WalkAway-96.
      Pneumoslide IgM kit was used for detection of atypical pathogens via indirect
      immunofluorescent assay. RESULTS: The predominant isolates in 360 patients with
      CAP were S. pneumoniae (36%), C. pneumoniae (18%), and M. pneumoniae (12%). A
      higher sensitivity was recorded for moxifloxacin, levofloxacin, macrolides, and
      cefepime. A higher of resistance was recorded for doxycycline, cephalosporins,
      and beta-lactam-beta-lactamase inhibitors. The predominant isolates in 318
      patients with HAP were, methicillin-resistant Staphylococcus aureus; MRSA (23%),
      K. pneumoniae (14%), and polymicrobial in 12%. A higher sensitivity was recorded
      for vancomycin, ciprofloxacin, and moxifloxacin. Very high resistance was
      recorded for beta-lactam-beta-lactamase inhibitors and cephalosporins. The
      predominant organisms in 376 patients with acute exacerbation of chronic
      obstructive pulmonary diseases (AECOPD) were H. influnzae (30%), S. pneumoniae
      (25%), and M. catarrhalis (18%). A higher sensitivity was recorded for
      moxifloxacin, macrolides and cefepime. A higher rate of resistance was recorded
      for aminoglycosides and cephalosporins. CONCLUSIONS: The most predominant
      bacteria for CAP in Upper Egypt are S. pneumoniae and atypical organisms, while
      that for HAP are MRSA and Gram negative bacteria. For acute exacerbation of COPD,
      H. influnzae was the commonest organism. Respiratory quinolones, macrolides, and
      cefepime are the most efficient antibiotics in treatment of LRTI in our locality.

PMID- 24106607
TI  - Vitamin d status in thalassemia major: an update.
AB  - The survival of patients with thalassemia major has progressively improved with
      advances in therapy; however, osteoporosis and cardiac dysfunction remain
      frequent complications. Adequate circulating levels of vitamin D are essential
      for optimal skeletal health and reducing fracture risk. Vitamin D deficiency and
      insufficiency is reported to be high in thalassemic patients in many countries
      despite the presence of good sunshine and routine prescription of 400-1,000 IU
      vitamin D per day. The risk of vitamin D deficiency in thalassemia and its
      relation to bone disease; including osteoporosis, rickets, scoliosis, spinal
      deformities and fractures as well as to cardiac dysfunction is discussed in this
      mini-review. Monitoring and maintaining normal serum level of 25-OH vitamin D
      through oral intake of vitamin D and early correction of VDD by oral or parental
      use of vitamin D may significantly improve bone mineral accretion and ameliorate
      cardiac function. 

PMID- 24106609
TI  - Prevalence of HPV High-Risk Genotypes in Three Cohorts of Women in Ouagadougou
      (Burkina Faso).
AB  - The development of cervical cancer is associated with high-risk Human papilloma
      viruses (HPV-HR). In sub-Saharan Africa cervical cancer is the most common cancer
      among women and the leading cause of death attributed to malignant tumors. This
      study aims to identify HPV genotypes within the 30'S and 50'S HPV families found
      in two previous studies from our laboratory, and to determine the prevalence of
      twelve HPV-HR genotypes in a population of women in Ouagadougou. The twelve HPV
      HR genotypes were determined by real-time multiplex PCR, in 180 samples from the
      general population and among a group of HIV-1 infected women. The most common
      genotypes found were HPV-35 (29.4%) and HPV-31 (26.1%) of the 30'S family, and
      HPV-52 (29.4%) and HPV-58 (20.6%) of the 50'S family. Multiple infections of HPV
      HR were observed in 78.03% of infected women. The frequencies of HPV genotypes
      from the 30'S and 50'S families were higher, while the genotypes HPV-16 and18
      were lower among the women in our study. 

PMID- 24106608
TI  - Proteolytic processing of von Willebrand factor by adamts13 and leukocyte
      proteases.
AB  - ADAMTS13 is a 190 kDa zinc protease encoded by a gene located on chromosome 9q34.
      This protease specifically hydrolyzes von Willebrand factor (VWF) multimers, thus
      causing VWF size reduction. ADAMTS13 belongs to the A Disintegrin And
      Metalloprotease with ThromboSpondin type 1 repeats (ADAMTS) family, involved in
      proteolytic processing of many matrix proteins. ADAMTS13 consists of numerous
      domains including a metalloprotease domain, a disintegrin domain, several
      thrombospondin type 1 (TSP1) repeats, a cysteine-rich domain, a spacer domain and
      2 CUB (Complement c1r/c1s, sea Urchin epidermal growth factor, and Bone
      morphogenetic protein) domains. ADAMTS13 cleaves a single peptide bond (Tyr1605
      Met1606) in the central A2 domain of the VWF molecule. This proteolytic cleavage
      is essential to reduce the size of ultra-large VWF polymers, which, when exposed
      to high shear stress in the microcirculation, are prone to form with platelets
      clumps, which cause severe syndromes called thrombotic microangiopathies (TMAs).
      In this review, we a) discuss the current knowledge of structure-function aspects
      of ADAMTS13 and its involvement in the pathogenesis of TMAs, b) address the
      recent findings concerning proteolytic processing of VWF multimers by different
      proteases, such as the leukocyte-derived serine and metallo-proteases and c)
      indicate the direction of future investigations. 

PMID- 24106610
TI  - Von Willebrand factor, angiodysplasia and angiogenesis.
AB  - The large multimeric glycoprotein Von Willebrand factor (VWF) is best known for
      its role in haemostasis; however in recent years other functions of VWF have been
      identified, indicating that this protein is involved in multiple vascular
      processes. We recently described a new role for VWF in controlling angiogenesis,
      which may have significant clinical implications for patients with Von Willebrand
      disease (VWD), a genetic or acquired condition caused by the deficiency or
      dysfunction of VWF. VWD can be associated with angiodysplasia, a condition of
      degenerative blood vessels often present in the gastrointestinal tract, linked to
      dysregulated angiogenesis. Angiodysplasia can cause severe intractable bleeding,
      often refractory to conventional VWD treatments. In this review we summarise the
      evidence showing that VWF controls angiogenesis, and review the angiogenic
      pathways which have been implicated in this process. We discuss the possible
      mechanisms though which VWF regulates angiopoietin-2 (Ang-2) and integrin
      alphavbeta3, leading to signalling through vascular endothelial growth factor
      receptor-2 (VEGFR2), one of the most potent activators of angiogenesis. We also
      review the evidence that links VWF with angiodysplasia, and how the newly
      identified function of VWF in controlling angiogenesis may pave the way for the
      development of novel therapies for the treatment of angiodysplasia in congenital
      VWD and in acquired conditions such as Heyde syndrome. 

PMID- 24106611
TI  - Elevation in Serum Concentration of Bone-Specific Alkaline Phosphatase without
      Elevation in Serum Creatinine Concentration Secondary to Adefovir Dipivoxil
      Therapy in Chronic Hepatitis B Virus Infection.
AB  - Of 168 patients with chronic hepatitis B virus (HBV) infection-related liver
      disease, 20 patients who had received 100 mg of lamivudine plus 10 mg/day of
      adefovir dipivoxil (ADV) (ADV group) and 124 patients who had received 0.5 mg/day
      of entecavir or 100 mg/day of lamivudine (non-ADV group) for >1 year were
      enrolled. For comparative analyses, 19 well-matched pairs were obtained from the
      groups by propensity scores. At the time of enrollment, serum creatinine and
      phosphate concentrations were similar between the ADV and non-ADV groups;
      however, urinary phosphate (P = 0.0424) and serum bone-specific alkaline
      phosphatase (BAP) (P = 0.0228) concentrations were significantly higher in the
      ADV group than in the non-ADV group. Serum BAP was significantly higher at the
      time of enrollment than before ADV administration in the ADV group (P = 0.0001),
      although there was no significant change in serum BAP concentration in the non
      ADV group. There was a significant positive correlation between the period of ADV
      therapy and DeltaBAP (R (2) = 0.2959, P = 0.0160). Serum BAP concentration
      increased before increase in serum creatinine concentration and was useful for
      early detection of adverse events and for developing adequate measures for
      continuing ADV for chronic HBV infection-related liver disease. 

PMID- 24106613
TI  - Ultrastructural changes of airway in murine models of allergy and diet-induced
      metabolic syndrome.
AB  - Studying ultrastructural changes could reveal novel pathophysiology of obese
      asthmatic condition as existing concepts in asthma pathogenesis are based on the
      histological changes of the diseased airway. While asthma is defined in
      functional terms, the potential of electron microscopy (EM) in providing cellular
      and subcellular detail is underutilized. With this view, we have performed
      transmission EM in the lungs from allergic mice that show key features of asthma
      and high-fat- or high-fructose-fed mice that mimicked metabolic syndrome to
      illustrate the ultrastructural changes. The primary focus was epithelial injury
      and metaplasia, which are cardinal features of asthma and initiate airway
      remodeling. EM findings of the allergically inflamed mouse lungs correlate with
      known features of human asthma such as increased mitochondria in airway smooth
      muscle, platelet activation and subepithelial myofibroblasts. Interestingly, we
      found a clear and unambiguous evidence to suggest that ciliated cells can become
      goblet cells using immunoelectron microscopy. Additionally, we show for the first
      time the stressed mitochondria in the bronchial epithelia of high-fat- or high
      fructose-fed mice even without allergen exposure. These results may stimulate
      interest in using EM in understanding novel pathological mechanisms for different
      subtypes of asthma including obese asthma. 

PMID- 24106615
TI  - Pharmacosomes: an emerging novel vesicular drug delivery system for poorly
      soluble synthetic and herbal drugs.
AB  - In the arena of solubility enhancement, several problems are encountered. A novel
      approach based on lipid drug delivery system has evolved, pharmacosomes.
      Pharmacosomes are colloidal, nanometric size micelles, vesicles or may be in the
      form of hexagonal assembly of colloidal drug dispersions attached covalently to
      the phospholipid. They act as befitting carrier for delivery of drugs quite
      precisely owing to their unique properties like small size, amphiphilicity,
      active drug loading, high entrapment efficiency, and stability. They help in
      controlled release of drug at the site of action as well as in reduction in cost
      of therapy, drug leakage and toxicity, increased bioavailability of poorly
      soluble drugs, and restorative effects. There has been advancement in the scope
      of this delivery system for a number of drugs used for inflammation, heart
      diseases, cancer, and protein delivery along with a large number of herbal drugs.
      Hence, pharmacosomes open new challenges and opportunities for improved novel
      vesicular drug delivery system. 

PMID- 24106614
TI  - UGT2B17 Polymorphism and Risk of Prostate Cancer: A Meta-Analysis.
AB  - Objective. Recent studies on the association between uridine
      diphosphosglucuronosyltransferases (UGTs) 2B17 polymorphism and risk of prostate
      cancer (PCa) showed inconclusive results. To clarify this possible association,
      we conducted a meta-analysis of published studies. Methods. We searched the
      published literature from PubMed, Embase, Google Scholar, and China National
      Knowledge Infrastructure (CNKI). According to our inclusion criteria, studies
      that observed the association between UGT2B17 polymorphism and PCa risk were
      included. The principal outcome measure was the adjusted odds ratio (OR) with 95%
      confidence interval (CI) for the risk of PCa associated with UGT2B17
      polymorphism. Results. A total of 6 studies with 7,029 subjects (3,839 cases and
      3,190 controls) were eligible for inclusion in the meta-analysis. Overall, there
      was a significant association between UGT2B17 polymorphism and increased risk of
      prostate cancer (OR = 1.74, 95% CI 1.14-2.64, P < 0.001). Similar results were
      found in the subgroup analyses by ethnicity and types of controls. Conclusion.
      This meta-analysis demonstrates that UGT2B17 polymorphism is associated with
      prostate cancer susceptibility, and it contributes to the increased risk of
      prostate cancer. 

PMID- 24106616
TI  - Gastrointestinal Elimination of Perfluorinated Compounds Using Cholestyramine and
      Chlorella pyrenoidosa.
AB  - Background. While perfluorinated compounds (PFCs) are a family of commonly used
      synthetic compounds with many applications, some PFCs remain persistent within
      the human body due, in part, to enterohepatic recirculation and renal tubular
      reabsorption. With increasing recognition of potential harm to human health
      associated with PFC bioaccumulation, interventions to facilitate elimination of
      these toxicants are welcome in order to potentially preclude or overcome illness.
      Minimal research has been undertaken thus far on methods to accelerate human
      clearance of PFCs. Methods. To test for possible oral treatments to hasten PFC
      elimination, a group of individuals with elevated PFC levels was treated with
      cholestyramine (CSM) and, after a break, was subsequently treated with Chlorella
      pyrenoidosa (CP). Stool samples were collected from all participants (i) prior to
      any treatment, (ii) during treatment with CSM, and (iii) during treatment with
      CP. Results. With CSM treatment, significant levels of three distinct PFCs were
      found in all stools, while levels were mostly undetectable prior to treatment.
      Following treatment with oral CP, undetectable or very low levels of all PFCs
      were noted in each sample tested. Conclusion. CSM appears to facilitate
      elimination of some common PFCs and may have some role in the clinical management
      of patients with accrued PFCs. 

PMID- 24106617
TI  - Multiple supplemental supernumerary premolars: unusual presentation in a
      nonsyndrome patient.
AB  - Supplementary teeth in the dental arch are a rare occurrence. Though they are
      mostly reported in association with syndromes they can also present in the
      absence of systemic pathology. This paper reports a case with multiple
      supernumerary teeth along with discussion of the frequency, types, complications,
      and management of such occurrence. 

PMID- 24106618
TI  - Multilocular unicystic ameloblastoma of mandible.
AB  - Introduction. We report a rare case of unicystic ameloblastoma (UA) of mandible
      which showed multilocular radiolucency on the left side of mandible on
      radiographic examination which is very unusual, and the majority of the cases of
      UAs till date has been reported of unilocular radiolucency. On histopathological
      examination, an odontogenic cystic lining that proliferates that intraluminally
      resembling ameloblastomatous epithelium was observed, leading to a definitive
      diagnosis of unicystic ameloblastoma. Case Presentation. A 42-year-old male
      patient presented with a swelling on the left side of the mandible extending from
      33 to 36. Radiographically, it showed a multilocular radiolucent lesion
      resembling odontogenic cyst; however, the final diagnosis was made on
      histopathological ground with the inclusion of radiological and clinical
      features. Conclusion. It can be concluded that at present, histopathologic
      examination is the most sensitive tool for differentiating between odontogenic
      cysts and UAs. However, both clinical and radiologic findings share equal
      contribution to the final diagnosis. 

PMID- 24106612
TI  - Waldenstrom macroglobulinemia: clinical and immunological aspects, natural
      history, cell of origin, and emerging mouse models.
AB  - Waldenstrom macroglobulinemia (WM) is a rare and currently incurable neoplasm of
      IgM-expressing B-lymphocytes that is characterized by the occurrence of a
      monoclonal IgM (mIgM) paraprotein in blood serum and the infiltration of the
      hematopoietic bone marrow with malignant lymphoplasmacytic cells. The symptoms of
      patients with WM can be attributed to the extent and tissue sites of tumor cell
      infiltration and the magnitude and immunological specificity of the paraprotein.
      WM presents fascinating clues on neoplastic B-cell development, including the
      recent discovery of a specific gain-of-function mutation in the MYD88 adapter
      protein. This not only provides an intriguing link to new findings that natural
      effector IgM(+)IgD(+) memory B-cells are dependent on MYD88 signaling, but also
      supports the hypothesis that WM derives from primitive, innate-like B-cells, such
      as marginal zone and B1 B-cells. Following a brief review of the clinical aspects
      and natural history of WM, this review discusses the thorny issue of WM's cell of
      origin in greater depth. Also included are emerging, genetically engineered mouse
      models of human WM that may enhance our understanding of the biologic and genetic
      underpinnings of the disease and facilitate the design and testing of new
      approaches to treat and prevent WM more effectively. 

PMID- 24106619
TI  - The use of bedside ultrasound in the evaluation of patients presenting with signs
      and symptoms of pulmonary embolism.
AB  - Evaluation of patients that present to the emergency department with concerns for
      the diagnosis of pulmonary embolism can be difficult. Modalities including
      computerized tomography (CT) of the chest, pulmonary angiography, and ventilation
      perfusion scans can expose patients to large quantities of radiation especially
      if the study has to be repeated due to poor quality. This is particularly a
      concern in the pregnant population that has an increased incidence of pulmonary
      embolism and may not be able to undergo multiple radiographic studies due to
      fetal radiation exposure. This paper presents a case of a pregnant patient with
      signs and symptoms concerning pulmonary embolism. The paper discusses the use of
      bedside ultrasound in the evaluation of patients with pulmonary embolism. 

PMID- 24106620
TI  - Esophageal plasmacytoma diagnosed in a patient presenting with cardiac symptoms:
      a novel case.
AB  - Extramedullary plasmacytoma is the uncommon phenomenon of a plasma cell neoplasm
      occurring outside of the bone marrow. Primary plasmacytoma is a rare occurrence
      in the gastrointestinal tract and exceptional to originate in the esophagus. We
      present a novel case of a 62-year-old man who presented to our emergency
      department with chest pain. A cardiovascular workup was negative, and an
      endoscopy was subsequently performed. The endoscopy findings showed evidence of
      Grade IV esophagitis with ulcerations extending from 25 cm to 32 cm.
      Histopathological examination revealed marked acute and chronic inflammation,
      granulation tissue, and overlying necroinflammatory exudate. However, sheets of
      plasma cells, some with prominent nucleoli, were also seen.
      Immunohistochemically, the plasma cells expressed CD138 and MUM1 and were IgG
      kappa restricted. A bone marrow biopsy was performed which was negative for
      involvement. This is a novel case of esophageal plasmacytoma diagnosed on
      endoscopy in a patient presenting with acute chest pain. 

PMID- 24106621
TI  - Morganella morganii Pericarditis in a Patient with Multiple Myeloma.
AB  - Purulent pericarditis caused by Morganella morganii is extremely rare. We report
      herein a case of a 61-year-old man who presented with chest pain and dyspnea
      fourteen days after chemotherapy for multiple myeloma. Echocardiogram and
      computed tomography revealed a massive pericardial effusion and associated
      cardiac tamponade. Pericardiocentesis was performed. Pericardial fluid was found
      to be purulent, and Morganella morganii was isolated from the fluid. The patient
      was successfully treated with antibiotic therapy and surgical drainage of the
      fluid. Morganella morganii should be considered a possible pathogen when
      immunocompromised patients develop purulent pericarditis. 

PMID- 24106622
TI  - Acute Acalculous Cholecystitis due to Viral Hepatitis A.
AB  - Inflammation of the gallbladder without evidence of calculi is known as acute
      acalculous cholecystitis (AAC). AAC is frequently associated with gangrene,
      perforation, and empyema. Due to these associated complications, AAC can be
      associated with high morbidity and mortality. Medical or surgical treatments can
      be chosen according to the general condition of the patient, underlying disease
      and agent. Particularly in acute acalculous cholecystitis cases, early diagnosis
      and early medical treatment have a positive effect on the patient and protect
      them from surgical trauma. ACC is a rare complication of acute viral hepatitis A.
      Herein, we present an adult patient of acalculous cholecystitis due to acute
      viral hepatitis A. She responded to the conservative management. 

PMID- 24106623
TI  - Neurenteric cysts found on the outer membrane of a subdural haematoma.
AB  - We report on a patient initially diagnosed with a chronic subdural haematoma that
      was resistant to treatment. After the second burr hole craniostomy within a half
      month failed to resolve the subdural haematoma (SDH), we performed a craniotomy
      to identify the point of bleeding. Macroscopic evaluation showed that most of the
      outer membrane of the SDH was transparent; however, further examination revealed
      the presence of multiple white regions. Pathologic examination showed that the
      white regions were fluid filled and surrounded by columnar ciliated epithelial
      cells. These lesions were pathologically diagnosed as neurenteric cysts. To our
      knowledge, this is the first report on a patient with neurenteric cysts found on
      the outer membrane of a CSDH. We agree that a craniotomy is a treatment of last
      resort for recurrent CSDHs; however, sometimes this procedure can be very useful
      for identifying underlying causes of obstinate SDHs as well as for their
      treatment. 

PMID- 24106624
TI  - Conservative treatment of a gossypiboma causing uterine wound dehiscence.
AB  - We present a rare case with gossypiboma following cesarean section which led to
      uterine wound dehiscence. A 30-year-old woman had been submitted to an emergency
      cesarean section 4 months previously at another hospital. Clinical and ultrasound
      findings revealed a large intra-abdominal mass and diffuse peritonitis. At
      laparotomy, a gossypiboma causing an abscess and uterine wound dehiscence with
      necrosis of the margins was detected. We performed repetitive wound debridements
      under broad-spectrum antibiotic cover and eventually resutured the incision.
      Although hysterectomy has so far been the choice of treatment in the literature
      once a uterine wound dehiscence had occurred, it was possible in this case to
      preserve the uterus. 

PMID- 24106625
TI  - Clinical experience of bronchoscopy-guided radiofrequency ablation for peripheral
      type lung cancer.
AB  - We have developed a new internal cooled electrode for radiofrequency ablation
      (RFA) (Japan Application no. 2006-88228) suitable for forceps channel
      bronchoscopy. Here, we present our clinical experience with bronchoscopy-guided
      RFA under computed tomography (CT) monitoring for patients with peripheral-type
      non-small-cell lung cancer (NSCLC). Bronchoscopy-guided RFA was performed in two
      patients (80 and 70 years old) with NSCLC, who had no lymph node involvement and
      distant metastases (T1N0M0), but not indicated for surgery because of other
      complications, such as advanced age, poor pulmonary function, and refusal of
      thoracic surgery. The locations of the tumors were right S2 and left S3,
      respectively. Although the tumors showed ground-glass opacity (GGO) with solid
      components in both cases, radiographic findings changed to reduced mass-like
      shadow and remained stable for 4 and 3.5 years after bronchoscopy-guided RFA. As
      the former case developed progressive disease on chest CT, bronchoscopy-guided
      RFA was repeated in the same lesion, resulting in no change for the subsequent 1
      year. There were no adverse reactions during the procedures. Thus, bronchoscopy
      guided RFA is a safe and feasible procedure that represents a potentially useful
      therapeutic tool in local control in medically inoperable patients with stage I
      NSCLC. 

PMID- 24106626
TI  - Retinal Detachment due to CrossFit Training Injury.
AB  - The purpose of this paper is to describe a traumatic retinal detachment occurring
      as a result of CrossFit training using an elastic exercise band. The patient
      sustained an ocular injury from an elastic band during CrossFit training,
      resulting in a giant retinal dialysis and retinal detachment, which were
      successfully repaired. Trainers and athletes need to be aware of the potential
      for ocular injury from elastic exercise bands and take appropriate precautions. 

PMID- 24106627
TI  - Sporadic occurrence of jarcho-levin syndrome in an ivorian newborn.
AB  - We report on an isolated chest-wall asymmetry with imaging findings of multiple
      vertebral and related rib defects in an Ivorian male newborn. He was born of a
      healthy and young couple without parental lineage, neither family malformative
      history nor teratogen exposure. This clinical presentation advocates Jarcho-Levin
      syndrome, a rare sporadic or familial disorder inherited as autosomal dominant or
      recessive mode and manifested by extensive vertebral segmentation defects with
      distinctive rib structural and morphological anomalies. According to our belief,
      this disorder has not been previously traced in the sub-Saharan African area. 

PMID- 24106628
TI  - Multicentric giant cell tumor of bone: synchronous and metachronous presentation.
AB  - A 27-year-old man treated 2.5 years ago for synchronous multicentric giant cell
      tumor of bone located at the right proximal humerus and the right 5th finger
      presented now with complaints of pain in his right hip and wrist of two-month
      duration. Radiology and magnetic resonance revealed multicentric giant cell tumor
      lesions of the right proximal femur, the left ileum, the right distal radius, and
      the left distal tibia. The patient has an eighteen-year history of a healed
      osteosarcoma of the right tibia that was treated with chemotherapy, resection,
      and allograft reconstruction. A literature review establishes this as the first
      reported case of a patient with synchronous and metachronous multicentric giant
      cell tumor who also has a history of osteosarcoma. 

PMID- 24106629
TI  - Sudden Bilateral Sensorineural Hearing Loss Associated with HLA A1-B8-DR3
      Haplotype.
AB  - Sudden sensorineural hearing loss may be present as a symptom in systemic
      autoimmune diseases or may occur as a primary disorder without another organ
      involvement (autoimmune inner ear disease). The diagnosis of autoimmune inner ear
      disease is still predicated on clinical features, and to date specific diagnostic
      tests are not available. We report a case of bilateral sudden hearing loss,
      tinnitus, intense rotatory vertigo, and nausea in a female patient in which the
      clinical manifestations, in addition to raised levels of circulating immune
      complexes, antithyroglobulin antibodies, and the presence of the HLA A1-B8-DR3
      haplotype, allowed us to hypothesize an autoimmune inner ear disease.
      Cyclosporine-A immunosuppressive treatment in addition to steroids helped in
      hearing recovery that occurred progressively with normalization of the hearing
      function after a five-month treatment. Cyclosporine-A could be proposed as a
      therapeutic option in case of autoimmune inner ear disease allowing the
      suspension of corticosteroids that, at high dose, expose patients to potentially
      serious adverse events. 

PMID- 24106630
TI  - Diagnostic consideration for sinonasal Wegener's granulomatosis clinically
      mistaken for carcinoma.
AB  - We report a case of Wegener's granulomatosis clinically mistaken for carcinoma in
      a 21-year-old girl presenting with an ulcerated mass of the nasopharynx
      associated with enlarged laterocervical nodes. The lesion was clinically
      suspected as malignant on the basis of clinical and radiological findings
      (namely, computed tomography scan and positron emission tomography). However,
      multiple biopsies were not conclusive for malignancy showing histological change
      suggestive of Wegener's granulomatosis. A serum determination of cANCA supported
      the diagnosis of Wegener's granulomatosis. Clinical findings and image studies
      suggested an erroneous diagnosis of malignancy whereas a definitive diagnosis of
      Wegener's granulomatosis was achieved only after repeated biopsies thus leading
      to a correct therapeutic approach. The Wegener granulomatosis must be added to
      the list of the differential diagnoses of the masses of the nasopharynx
      associated with or without enlarged laterocervical nodes. 

PMID- 24106631
TI  - Acute MRSA sinusitis with intracranial extension and marginal vancomycin
      susceptibility.
AB  - Methicillin resistant Staphylococcus aureus (MRSA) is increasingly being
      described as a cause of acute sinusitis. We present a patient with acute MRSA
      sinusitis complicated by rapid intracranial extension, marginal vancomycin
      susceptibility (MIC = 2 mg/L), delayed drainage of intracranial abscess, and
      subsequent development of rifampin resistance. Given the relatively high risk of
      intracranial extension of severe acute bacterial sinusitis and high mortality
      associated with invasive MRSA infections, we suggest early surgical drainage of
      intracranial abscesses in these circumstances. We believe this is important given
      the limited intracranial penetration of currently available treatment options for
      MRSA, especially those with a vancomycin minimal inhibitory concentration (MIC)
      of >=2 mg/L. 

PMID- 24106632
TI  - Castleman disease: an unexpected cause of a solitary pleural mass.
AB  - Castleman disease (CD) is a rare benign lymphoproliferative disorder, the
      etiology of which is unclear. Clinically it may manifest as localized disease
      (unicentric) or disseminated disease (multicentric). CD occurs in the thorax in
      70% of cases, abdomen and pelvis in 15%, and in the neck in 10-15% of cases. We
      present a case of a pleural mass located posteriorly in a paraspinal location,
      which was discovered incidentally in a 50-year-old man and was subsequently
      resected followed by an unexpected diagnosis of Castleman disease on histological
      examination. In this report, we review the clinical and histological findings in
      a rare presentation of Castleman disease and discuss the findings in this case as
      part of an overall review of the typical radiological findings seen in Castleman
      disease. 

PMID- 24106633
TI  - An Unusual Case of Stercoral Perforation in a Patient with 86 cm of Small Bowel.
AB  - A 77-year-old male who previously had extensive enterectomy due to ischaemic gut
      with loss of all but 86 cm of jejunum in addition to a right hemicolectomy
      presented to the emergency department (ED) with abdominal pain and constipation
      of 12-day duration. Abdominal imaging with X-ray and CT revealed pneumoperitoneum
      in addition to a grossly redundant and faecally loaded colon. At laparotomy,
      rectal perforation was found. In view of the patient's advanced age,
      comorbidities, and the absence of intraperitoneal faecal contamination, manual
      disimpaction followed by wedge resection and primary closure of the perforation
      was done. On postop day 11, a perforation in the sigmoid colon with free
      subdiaphragmatic gas was picked up on CT after a work up for abdominal
      tenderness. In the absence of peritonism and other signs of deterioration,
      conservative management was chosen with subsequent uneventful recovery for the
      patient. 

PMID- 24106634
TI  - Isolated pulmonary infective endocarditis with septic pulmonary embolism
      complicating a right ventricular outflow tract obstruction: scarce and devious
      presentation.
AB  - We present a case of a fifty-three-year-old male who presented with severe
      sepsis. He had been treated as a pneumonia patient for five months before the
      admission. Investigations revealed isolated pulmonary valve endocarditis and
      septic pulmonary embolism in addition to undiagnosed right ventricular outflow
      tract (RVOT) obstruction. The patient underwent surgery for the relief of RVOT
      obstruction by substantial muscle resection of the RVOT, pulmonary artery
      embolectomy, pulmonary valve replacement, and reconstruction of RVOT and main
      pulmonary artery with two separate bovine pericardial patches. He was discharged
      from our hospital after 6 weeks of intravenous antibiotics. He recovered well on
      follow-up 16 weeks after discharge. A high-suspicion index is needed to diagnose
      right-side heart endocarditis. Blood cultures and transesophageal echocardiogram
      are the key diagnostic tools. 

PMID- 24106635
TI  - Strangulation and necrosis of an epiploic appendage of the sigmoid colon in a
      right inguinal hernia.
AB  - An epiploic appendage of the sigmoid colon is considered to be an unusual type of
      inguinal hernia content. The strangulation of a sigmoid colon appendage into a
      right inguinal hernia is exclusively rare. We present a case of an 81-year-old
      female patient with severe cardiovascular comorbidities who was urgently admitted
      after an episode of strangulation and subsequent spontaneous reduction of a right
      inguinal hernia. The condition of the patient was stable, and an urgent operation
      was not indicated for three days after admission. However, we had to operate
      because the hernia strangulation recurred. In the hernia sac, a free fatty body
      (a separated and saponified epiploic appendage of the colon) and a strangulated
      epiploic appendage of dolichosigmoid, with signs of necrosis, were found. Removal
      of the free fatty body and necrotic epiploic appendage and subsequent anterior
      wall inguinal hernioplasty were successfully performed. In the world literature,
      this case may be the first report of a sigmoid epiploic appendage strangulation
      in a right inguinal hernia that is well documented by photography. 

PMID- 24106636
TI  - Liver transplantation using a graft from a donor with situs inversus totalis: a
      case report and review of the literature.
AB  - It is critical to effectively use every available organ to meet the increasing
      demands for liver transplantation. Situs inversus is a rare congenital anomaly
      caused by obstruction of viscus rotation during embryonic development. Situs
      inversus was once regarded as a contraindication to liver transplantation because
      of the technical difficulties associated with the unique vascular anatomy and
      concern about achieving accurate graft positioning. Here, we present a successful
      case of liver transplantation using a graft from a donor with situs inversus
      totalis. The related experience will contribute to opening up new realms for the
      use of such rare organ resources. 

PMID- 24106637
TI  - Spontaneous Retroperitoneal Hemorrhage (Wunderlich Syndrome) due to Large Upper
      Pole Renal Angiomyolipoma: Does Robotic-Assisted Laparoscopic Partial Nephrectomy
      Have a Role in Primary Treatment?
AB  - Spontaneous rapture with consequent retroperitoneal hemorrhage (Wunderlich's
      syndrome) is the complication mostly feared from large renal angiomyolipomas
      (RAMLs). In hemodynamic stable patients, minimal invasive therapies have
      superseded open surgery as the mainstay of treatment, with contemporary cases
      mostly treated by selective arterial embolization. Robotic-assisted laparoscopic
      partial nephrectomy (RALPN) is an established minimal access treatment that has
      been used in the past for benign and malignant lesions of the kidney in the
      elective setting, but rarely in urgent situations as primary treatment. We
      present a case of a ruptured RAML in a young female treated effectively by RALPN.

PMID- 24106638
TI  - Giant renal artery aneurysms: decision-making dilemmas.
AB  - A case of a 10 cm giant renal artery aneurysm in an 81-year-old lady is herein
      reported. The patient presented as an incidental finding on an abdominal
      ultrasound with an aneurysm which was large, soft, egg-shell-like, and bilobular
      with a cauliflower-type pattern invading the parenchyma of the renal substance
      and extending caudally. A right nephrectomy was carried out, and the patient made
      an uneventful recovery. This paper reviews the options for treatment of giant
      renal artery aneurysms and highlights the benefit of a planned nephrectomy once
      there is adequate renal reserve in the opposite kidney using a midline approach
      for right-sided giant renal artery aneurysms and a left-sided flank approach for
      left-sided aneurysms. 

PMID- 24106639
TI  - Spontaneous-idiopathic left anterior descending artery dissection: is watchful
      waiting better than immediate stenting?
AB  - Spontaneous coronary artery dissection (SCAD) is a rare, complex disease,
      nowadays poorly understood yet. The lack of firm recommendations about this issue
      is a great limitation which makes any therapeutic decision controversial. The
      case described is that of a young, otherwise healthy woman, who presented with an
      ostial dissection of the left anterior descending (LAD) artery. Due to patient's
      stable clinical and hemodynamic parameters, we used a cautious approach based on
      watchful waiting and medical therapy, postponing stenting in order to achieve a
      partial vessel reopening with a more comfortable access to PCI. 

PMID- 24106640
TI  - The evolving treatment options for diabetic macular edema.
AB  - Diabetic retinopathy (DR) is the leading cause of vision loss in working-age
      adults, and diabetic macular edema (DME) is the most common cause of visual
      impairment in individuals with DR. This review focuses on the pathophysiology,
      previous treatment paradigms, and emerging treatment options in the management of
      DME. 

PMID- 24106641
TI  - Thyroid and aging or the aging thyroid? An evidence-based analysis of the
      literature.
AB  - Thyroid hormone production, metabolism, and action change with aging. The
      reference ranges for serum thyrotropin and thyroid hormones are derived mainly
      from younger populations. Thus, the prevalence of subclinical thyroid dysfunction
      is increased greatly in the elderly. However, it is unclear whether mild thyroid
      dysfunction in the elderly is associated with adverse outcomes. In this review,
      we discuss current evidence-based literature on thyroid function in the elderly
      and whether subclinical thyroid dysfunction in the elderly should be treated. 

PMID- 24106642
TI  - Neurobehavioral deficits and parkinsonism in occupations with manganese exposure:
      a review of methodological issues in the epidemiological literature.
AB  - Exposure to manganese (Mn) is associated with neurobehavioral effects. There is
      disagreement on whether commonly occurring exposures in welding, ferroalloy, and
      other industrial processes produce neurologically significant neurobehavioral
      changes representing parkinsonism. A review of methodological issues in the human
      epidemiological literature on Mn identified: (1) studies focused on idiopathic
      Parkinson disease without considering manganism, a parkinsonian syndrome; (2)
      studies with healthy worker effect bias; (3) studies with problematic statistical
      modeling; and (4) studies arising from case series derived from litigation.
      Investigations with adequate study design and exposure assessment revealed
      consistent neurobehavioral effects and attributable subclinical and clinical
      signs and symptoms of impairment. Twenty-eight studies show an exposure-response
      relationship between Mn and neurobehavioral effects, including 11 with continuous
      exposure metrics and six with three or four levels of contrasted exposure. The
      effects of sustained low-concentration exposures to Mn are consistent with the
      manifestations of early manganism, i.e., consistent with parkinsonism. This is
      compelling evidence that Mn is a neurotoxic chemical and there is good evidence
      that Mn exposures far below the current US standard of 5.0 mg/m(3) are causing
      impairment. 

PMID- 24106643
TI  - Dermal exposure associated with occupational end use of pesticides and the role
      of protective measures.
AB  - BACKGROUND: Occupational end users of pesticides may experience bodily absorption
      of the pesticide products they use, risking possible health effects. The purpose
      of this paper is to provide a guide for researchers, practitioners, and policy
      makers working in the field of agricultural health or other areas where
      occupational end use of pesticides and exposure issues are of interest. METHODS:
      This paper characterizes the health effects of pesticide exposure, jobs
      associated with pesticide use, pesticide-related tasks, absorption of pesticides
      through the skin, and the use of personal protective equipment (PPE) for reducing
      exposure. CONCLUSIONS: Although international and national efforts to reduce
      pesticide exposure through regulatory means should continue, it is difficult in
      the agricultural sector to implement engineering or system controls. It is clear
      that use of PPE does reduce dermal pesticide exposure but compliance among the
      majority of occupationally exposed pesticide end users appears to be poor. More
      research is needed on higher-order controls to reduce pesticide exposure and to
      understand the reasons for poor compliance with PPE and identify effective
      training methods.

PMID- 24106644
TI  - Occupational dermatoses by type of work in Greece.
AB  - BACKGROUND: To elucidate the relationship between seven occupational dermatoses
      (ODs) and 20 types of work in Greece. METHODS: This was a prevalence
      epidemiologic study of certain ODs among 4,000 workers employed in 20 types of
      enterprise, in 104 companies, in 2006-2012, using data from company medical
      records, questionnaires, occupational medical, and special examinations. The
      chi(2) test was applied to reveal statistically significant relationships between
      types of enterprises and occurrence of ODs. RESULTS: A high percentage (39.9%) of
      employees included in the study population suffered from ODs. The highest
      prevalence rates were noted among hairdressers (of contact dermatitis: 30%),
      cooks (of contact dermatitis: 29.5%), bitumen workers (of acne: 23.5%), car
      industry workers (of mechanical injury: 15%), construction workers (of contact
      urticaria: 29.5%), industrial cleaning workers (of chemical burns: 13%), and
      farmers (of malignant tumors: 5.5%). We observed several statistical significant
      correlations between ODs (acute and chronic contact dermatitis, urticaria,
      mechanical injury, acne, burns, skin cancer) and certain types of enterprises.
      There was no statistically significant correlation between gender and prevalence
      of ODs, except for dermatoses caused by mechanical injuries afflicting mainly men
      [chi(2) (1) = 13.40, p < 0.001] and for chronic contact dermatitis [chi(2) (1) =
      5.53, p = 0.019] afflicting mainly women. CONCLUSION: Prevalence of ODs is high
      in Greece, contrary to all official reports by the Greek National Institute of
      Health. There is a need to introduce a nationwide voluntary surveillance system
      for reporting ODs and to enhance skin protection measures at work.

PMID- 24106645
TI  - Stochastic resonance whole-body vibration, musculoskeletal symptoms, and body
      balance: a worksite training study.
AB  - BACKGROUND: Stochastic resonance whole-body vibration training (SR-WBV) was
      tested to reduce work-related musculoskeletal complaints. METHODS: Participants
      were 54 white-collar employees of a Swiss organization. The controlled crossover
      design comprised two groups each given 4 weeks of exercise and no training during
      a second 4-week period. Outcome was daily musculoskeletal well-being,
      musculoskeletal pain, and surefootedness. In addition, participants performed a
      behavioral test on body balance prior to when SR-WBV started and after 4 weeks of
      SR-WBV. RESULTS: Across the 4-week training period, musculoskeletal well-being
      and surefootedness were significantly increased (p < 0.05), whereas
      musculoskeletal pain was significantly reduced only in those who reported low
      back pain during the last 4 weeks prior to the study (p < 0.05). Body balance was
      significantly increased by SR-WBV (p < 0.05). CONCLUSION: SR-WBV seems to be an
      efficient option in primary prevention of musculoskeletal complaints and falls at
      work.

PMID- 24106646
TI  - Testing of common electromagnetic environments for risk of interference with
      cardiac pacemaker function.
AB  - BACKGROUND: Cardiac pacemakers are known to be susceptible to strong
      electromagnetic fields (EMFs). This in vivo study investigated occurrence of
      electromagnetic interference with pacemakers caused by common environmental
      sources of EMFs. METHODS: Eleven volunteers with a pacemaker were exposed to EMFs
      produced by two mobile phone base stations, an electrically powered commuter
      train, and an overhead high voltage transmission lines. All the pacemakers were
      programmed in normal clinically selected settings with bipolar sensing and pacing
      configurations. RESULTS: None of the pacemakers experienced interference in any
      of these exposure situations. However, often it is not clear whether or not
      strong EMFs exist in various work environments, and hence an individual risk
      assessment is needed. CONCLUSIONS: Modern pacemakers are well shielded against
      external EMFs, and workers with a pacemaker can most often return to their
      previous work after having a pacemaker implanted. However, an appropriate risk
      assessment is still necessary after the implantation of a pacemaker, a change of
      its generator, or major modification of its programming settings.

PMID- 24106647
TI  - Descriptive Study of Occupational Accidents and their Causes among Electricity
      Distribution Company Workers at an Eight-year Period in Iran.
AB  - BACKGROUND: Occupational accidents are unplanned events that cause damage. The
      socio-economic impacts and human costs of accidents are tremendous around the
      world. Many fatalities happen every year in workplaces such as electricity
      distribution companies. Some electrical injuries are electrocution, electric
      shock, and burns. This study was conducted in an electricity distribution company
      (with rotational 12-hour shift work) in Iran during an 8-year period to survey
      descriptive factors of injuries. METHODS: Variables collected included accident
      time, age of injured worker, employment type, work experience, injury cause,
      educational background, and other information about accidents. RESULTS: Results
      indicated that most of the accidents occurred in summer, and 51.3% were during
      shift work. Worker negligence (malpractice) was the cause of 75% of deaths. Type
      of employment had a significant relationship with type of injuries (p < 0.05).
      Most injuries were electrical burns. CONCLUSION: High rate of accidents in summer
      may be due to the warm weather or insufficient professional skills in seasonal
      workers. Shift workers are at risk of sleep complaints leading to a high rate of
      work injuries. Acquiring knowledge about safety was related to job experiences.
      Temporary workers have no chance to work all year like permanent workers,
      therefore impressive experiences may be less in them. Because the lack of
      protective equipment and negligence are main causes of accidents, periodical
      inspections in workshops are necessary.

PMID- 24106648
TI  - A training intervention for supervisors to support a work-life policy
      implementation.
AB  - BACKGROUND: Effective policy implementation is essential for a healthy workplace.
      The Ryan-Kossek 2008 model for work-life policy adoption suggests that
      supervisors as gatekeepers between employer and employee need to know how to
      support and communicate benefit regulations. This article describes a workplace
      intervention on a national employee benefit, Family and Medical Leave Act (FMLA),
      and evaluates the effectiveness of the intervention on supervisor knowledge,
      awareness, and experience with FMLA. METHODS: The intervention consisted of
      computer-based training (CBT) and a survey measuring awareness and experience
      with FMLA. The training was administered to 793 county government supervisors in
      the state of Oregon, USA. RESULTS: More than 35% of supervisors reported no
      previous training on FMLA and the training pre-test revealed a lack of knowledge
      regarding benefit coverage and employer responsibilities. The CBT achieved: (1) a
      significant learning effect and large effect size of d = 2.0, (2) a positive
      reaction to the training and its design, and (3) evidence of increased knowledge
      and awareness regarding FMLA. CONCLUSION: CBT is an effective strategy to
      increase supervisors' knowledge and awareness to support policy implementation.
      The lack of supervisor training and knowledge of an important but complex
      employee benefit exposes a serious impediment to effective policy implementation
      and may lead to negative outcomes for the organization and the employee,
      supporting the Ryan-Kossek model. The results further demonstrate that long-time
      employees need supplementary training on complex workplace policies such as FMLA.

PMID- 24106649
TI  - The top 100 cited articles in essential tremor.
AB  - BACKGROUND: The impact of scientific articles is proportional to the citations
      they have received. Our aim was to identify and analyze the top 100 cited
      articles on essential tremor (ET). METHODS: The Institute for Scientific
      Information Web of Knowledge Database and the 2012 Journal Citation Report
      Science Editions were used to retrieve the 100 top-cited articles published about
      ET from 1960 to April 2013. Information was collected by the Analyze Tool on the
      Web of Science, including number of citations, publication title, journal name,
      publication year, and country and institution of origin. Additional analyses were
      then performed to determine authorship, article type, study design, and level of
      evidence. RESULTS: ALMOST HALF OF THE ARTICLES WERE RETRIEVED FROM TWO JOURNALS:
      Neurology (n = 31) and Movement Disorders (n = 18). The top 100 articles were
      published between 1960 and 2010, with case series being the most common study
      design (n = 34). According to their countries of origin, more than half of the
      articles were generated in the United States (n = 54), which led the list.
      Columbia University in the United States produced the largest number of ET
      articles (n = 19), followed by the University of Kansas (n = 18). The most
      frequent first authors of the top-cited articles in ET were E.D. Louis (n = 27)
      and W.C. Koller (n = 15), who together accounted for 42% of the articles on the
      list. DISCUSSION: It is important to acknowledge the top-cited articles as they
      mark key topics and advances in ET.

PMID- 24106650
TI  - Tourette syndrome and consciousness of action.
AB  - BACKGROUND: Tourette syndrome (TS) is a neuropsychiatric disorder characterized
      by the chronic presence of multiple motor tics and at least one vocal/phonic tic
      since childhood. Tics typically change and vary in both intensity and severity
      over time, with remission and exacerbation common. In the vast majority of
      patients, tic expression is characteristically accompanied by discomforting
      bodily sensations, known as sensory phenomena or premonitory urges. METHODS: We
      reviewed the existing literature on premonitory urges associated with the sense
      of voluntariness of action in TS. RESULTS: Although the wish to move is perceived
      by the patient as involuntary, the decision to release the tic is often perceived
      by the patient as a voluntary capitulation to the subjective urge. Most patients
      with TS can exert a degree of control over the urge and constantly try to inhibit
      the movement. Based on these features, it has been suggested that tics performed
      in response to an urge to move should be classified as 'unvoluntary', as opposed
      to voluntary or involuntary acts. However, recent experimental data suggest that
      the brain areas involved in the generation of the wish to act show considerable
      overlap between healthy subjects and patients with TS. DISCUSSION: The
      simultaneous presence of both voluntary and involuntary aspects in the expression
      of tic symptoms by patients with TS is consistent with the hypothesis that tics
      can have the same neurophysiologic substrate as voluntary acts, even though they
      are misperceived as being involuntary. This reinforces the view of TS as a
      hyperkinetic movement disorder primarily affecting the conscious experience of
      action.

PMID- 24106652
TI  - Welcome, readers!

PMID- 24106651
TI  - Pediatric Autoimmune Neuropsychiatric Disorders Associated with Streptococcal
      Infections (PANDAS): An Evolving Concept.
AB  - Pediatric autoimmune neuropsychiatric disorders associated with streptococcus
      infections (PANDAS) originated from the observational work of Swedo and
      collaborators, who formalized their definition in 1998 in a set of operational
      criteria. The application of these criteria, which focuses on tics and obsessive
      compulsive symptoms as core symptoms, has encountered difficulties, eventually
      leading to a high rate of misdiagnosis. In particular, the core feature
      represented by the association between newly diagnosed infections and
      neuropsychiatric symptom relapses in youths with this diagnosis could not be
      demonstrated by longitudinal studies. Exploratory studies aiming to identify
      clinical or cognitive features that could discriminate PANDAS from other
      pediatric obsessive-compulsive and tic disorders present methodological
      limitations, and therefore are not conclusive. Other behavioral features, in
      addition to obsessive-compulsive symptoms and tics, have been included in
      pediatric acute-onset neuropsychiatric syndromes (PANS) and childhood acute
      neuropsychiatric syndromes (CANS), two new concepts recently proposed in order to
      define a much broader clinical spectrum encompassing etiologically diverse
      entities. Given the uncertainties on the clinical definition of PANDAS, it is not
      surprising that evidence in support of a post-infectious, immune-mediated
      pathophysiology is also insufficient. Anti-dopamine receptor antibodies might be
      relevant to both Sydenham's chorea (SC)-the prototypical post-streptococcal
      neuropsychiatric disorder-and some rare forms of encephalitis targeting the basal
      ganglia specifically, but studies exploring their association with children
      fulfilling Swedo's criteria for PANDAS have been inconclusive. Moreover, we lack
      evidence in favor of the efficacy of antibiotic prophylaxis or tonsillectomy in
      patients fulfilling Swedo's criteria for PANDAS, whereas a response to immune
      mediated treatments like intravenous immunoglobulins has been documented by one
      study, but needs replication in larger trials. Overall, the available evidence
      does not convincingly support the concept that PANDAS are a well-defined,
      isolated clinical entity subdued by definite pathophysiological mechanisms;
      larger, prospective studies are necessary to reshape the nosography and disease
      mechanisms of post-streptococcal acute neuropsychiatric disorders other than SC.
      Research is also under way to shed further light on a possible relationship
      between streptococcal infections, other biological and psychosocial stressors,
      and the complex pathobiology of chronic tic disorders. 

PMID- 24106653
TI  - The "bagel head" cosmetic modification: myths and medical complications for
      dermatologists to consider.
AB  - On September 23, 2012, the television program Taboo on the National Geographic
      Channel featured individuals in Tokyo undergoing the "bagel head" cosmetic
      modification. Dermatologists may encounter patients who undergo the bagel head
      procedure and subsequently present with a cutaneous infection. The purpose of
      this article is to delineate the bagel head procedure, note responses to
      sensationalist claims made by the media about this procedure, and discuss
      potential medical complications from this procedure. Specialists and primary care
      physicians who encounter reports of a specific extreme body modification for the
      first time should review discussions of the modification by its critics and
      advocates in order to assess potential medical complications from the procedure
      more accurately. 

PMID- 24106654
TI  - Waldenstrom macroglobulinaemia presenting as tingling ulcers on the feet.
AB  - A 56-year-old man presented with tingling ulcers on the feet. On further skin
      examination, papules on the knees were observed. Biopsies revealed extravascular
      eosinophilic deposits of IgM, and Waldenstrom macroglobulinaemia was diagnosed.
      The skin manifestations have resolved with chemotherapy. Peripheral neuropathy
      and storage papules are rare manifestations of Waldenstrom's macroglobulinaemia. 

PMID- 24106655
TI  - Microscopic examination of normal nail clippings.
AB  - BACKGROUND: Nail clipping analysis for diagnosing causes of onychodystrophy other
      than onychomycosis is investigated to a very small extent. In order to achieve
      acceptance as a diagnostic method for any kind of nail abnormalities, normal
      microscopic parameters have to be established first. In most reported cases, nail
      plates were fixed in formalin with processing of the specimens with routine
      automated histotechnique. METHODOLOGY: Fifteen pairs of normal nails were
      studied. One nail fragment was placed in a container with formalin, and the other
      was kept dry in a proper receptacle. Fixed specimens were submitted to standard
      automated tissue processing (formalin group) and dry specimens were directly
      embedded in paraffin (dry group). Several microscopic parameters were analyzed.
      RESULTS: Nail plate thickness ranged from 0.25 to 0.50 mm (mean 0.36 mm) and
      subungual region from 0 to 0.31 mm (mean 0.11 mm). Forty-one percent of cases
      presented onychokaryosis, and hypereosinophilic nuclear shadows were detected in
      63%, statistically more frequent in the dry group (p=0.002). Parakeratosis was
      present in 86% of nails varying from 1 to 13 layers (mean 5.6). None of the nails
      presented fungi, neutrophils, and blood or serum collections. Bacteria were seen
      in 60% of specimens. Both groups yielded adequate microscopic preparations for
      analysis with no statistical difference in the dryness or hardness of specimens
      or difficulty in cutting the paraffin blocks (p=1). CONCLUSION: These microscopic
      findings of a normal population can be used as parameters for evaluating any
      cause of onychodystrophy. The dry method is faster and cheaper and yields
      adequate slide preparations for microscopic analysis of nail clippings.

PMID- 24106656
TI  - Multiple confluent reddish nodules.

PMID- 24106657
TI  - A reticular pigmented rash on the lower leg.

PMID- 24106658
TI  - Dermoscopy: What is your diagnosis?

PMID- 24106659
TI  - Balloon cell melanoma in primary care practice: a case report.
AB  - A case of balloon cell melanoma encountered in a primary care skin cancer
      practice in Melbourne, Australia is presented. The presenting lesion was 6 mm in
      diameter, ulcerated, non-pigmented and without any algorithmic clues to melanoma.
      However the presence of terminal hairs caused the clinician to suspect that it
      was melanocytic. The lesion was reported as a balloon cell melanoma, Clark level
      4, Breslow thickness 2 mm with a mitotic index of 4 per square mm. This is an
      extremely rare melanoma subtype. Author DW has encountered only two cases in a
      career involving in excess of one million signed out dermatopathology reports. A
      search of the literature has not discovered any previously published dermatoscopy
      images of a balloon cell melanoma. 

PMID- 24106660
TI  - Review of neoplastic mimics in dermatopathology, by mark R. Wick and james w.
      Patterson.

PMID- 24106661
TI  - Cytotoxic Compounds from Brucea mollis.
AB  - Ten compounds, including soulameanone (1), isobruceine B (2), 9-methoxy-canthin-6
      one (3), bruceolline F (4), niloticine (5), octatriacontan-1-ol (6), bombiprenone
      (7), alpha-tocopherol (8), inosine (9), and apigenin 7-O-beta-D-glucopyranoside
      (10), were isolated from the leaves, stems, and roots of Brucea mollis Wall. ex
      Kurz. Their structures were determined using one-and two-dimensional NMR
      spectroscopy and mass spectrometry. All compounds were evaluated for their
      cytotoxic activity against KB (human carcinoma of the mouth), LU-1 (human lung
      adenocarcinoma), LNCaP (human prostate adeno-carcinoma), and HL-60 (human
      promyelocytic leukemia) cancer cell lines. Compound 2 showed significant
      cytotoxic activity against KB, LU-1, LNCaP, and HL-60 cancer cells with IC50
      values of 0.39, 0.40, 0.34, and 0.23 MUg/mL, respectively. In addition, compounds
      3 and 5 showed significant cytotoxic activity against KB, LU-1, LNCaP, and HL-60
      cancer cells with IC50 values around 1-4 MUg/mL. Compounds 9-methoxycanthin-6-one
      (3) and niloticine (5) have been discovered for the first time from the Brucea
      genus.

PMID- 24106662
TI  - Preparation and First Preclinical Evaluation of [(18)F]FE@SNAP: A Potential PET
      Tracer for the Melanin-Concentrating Hormone Receptor-1 (MCHR1).
AB  - The melanin-concentrating hormone (MCH) system is a new target for the treatment
      of human disorders. Since the knowledge of the MCH system's involvement in a
      variety of pathologies (obesity, diabetes, and deregulation of metabolic feedback
      mechanism) is based on in vitro or preclinical studies, a suitable positron
      emission tomography (PET) tracer needs to be developed. We herein present the
      preparation and first preclinical evaluation of [(18)F]FE@SNAP - a new PET tracer
      for MCH receptor-1 (MCHR1). The synthesis was performed using a microfluidic
      device. Preclinical evaluation included binding affinity, plasma stability,
      plasma free fraction, stability against the cytochrome P-450 (CYP450) system
      using liver microsomes, stability against carboxyl-esterase, and methods to
      assess the penetration of the blood-brain barrier (BBB) such as logD analysis and
      immobilized artificial membrane (IAM) chromatography. Levels at 374 +/- 202 MBq
      [(18)F]FE@SNAP were obtained after purification. The obtained K d value of
      [(18)F]FE@SNAP was 2.9 nM. [(18)F]FE@SNAP evinced high stability against
      carboxylesterase, CYP450 enzymes, and in human plasma. LogD (3.83) and IAM
      chromatography results (Pm=0.51) were in the same range as for known BBB
      penetrating compounds. The synthesis of [(18)F]FE@SNAP was reliable and
      successful. Due to high binding affinity and stability, [(18)F]FE@SNAP is a
      promising tracer for MCHR1.

PMID- 24106663
TI  - Synthesis and Biological Evaluation of Novel Alkyl-Imidazolyl Carbinols and their
      Esters: Potent Antimycotics.
AB  - A novel series of imidazol-5-yl carbinols and their 4-chlorobenzoyl esters has
      been synthesized by the Grignard reaction and subsequent esterification. These
      compounds were screened for their antimicrobial activities in an agar diffusion
      assay. The compounds with C10 to C12-alkyl side chains displayed significant
      antimycotic activity.

PMID- 24106664
TI  - Synthesis and characterization of potential dimers of gatifloxacin - an
      antibacterial drug.
AB  - Gatifloxacin is an antibacterial agent belonging to the fourth-generation
      fluoroquinolone family. Four piperazine-linked fluoroquinolone dimers of
      Gatifloxacin were observed during the laboratory process for Gatifloxacin and
      they were identified. The present work describes the origin, synthesis,
      characterization, and control of these dimers along with the synthesis of
      Despropylene Gatifloxacin (metabolite).

PMID- 24106665
TI  - Synthesis of 1,2,3-Triazole Derivatives and Evaluation of their Anticancer
      Activity.
AB  - Anticancer screening of several 1,2,3-triazoles with heterocyclic fragments has
      been performed. The 1,2,3-triazole derivatives were synthesized from available
      starting materials according to convenient synthetic procedures. The antitumor
      activity of the synthesized compounds was tested in vitro by the National Cancer
      Institute in NCI60 cell lines. It was observed that some compounds showed slight
      anticancer activity. One of them possessed a moderate activity against melanoma,
      colon, and breast cancer. Standard COMPARE analysis was performed at the GI50
      level.

PMID- 24106666
TI  - How to solve the problems of docking into a symmetric binding site: the example
      of the HERG channel.
AB  - Many proteins, such as the hERG K(+) channel or the HIV-1 protease, have a high
      degree of rotational symmetry. If the binding site of a ligand is composed of
      symmetrical subunits, the analysis of the docking poses of ligands is quite
      challenging. In the case of hERG, the four-fold symmetry of the entire channel is
      fully reflected in the binding site, which allows up to four poses with different
      coordinates of the ligand, but an identical interaction pattern. In light of our
      docking studies into the hERG potassium channel, we developed an algorithm
      (ROTALI) to detect the poses that are duplicates due to the symmetry of the
      channel. This led to a reduction in the number of poses to be considered in the
      subsequent steps by up to 52%.

PMID- 24106667
TI  - Identification and characterization of process-related impurities of trans
      resveratrol.
AB  - This article deals with the identification and characterization of process
      related impurities of trans-resveratrol (3,5,4'-trihydroxystilbene), which
      exhibits several health benefits, including cancer prevention. During the
      synthesis of the bulk drug resveratrol, three new impurities were observed. The
      impurities were detected using the high-performance liquid chromatographic (HPLC)
      method, whose area percentages ranged from 0.05 to 0.3%. A systematic study was
      carried out to characterize them. These impurities were isolated by preparative
      HPLC and characterized by spectral data, subjected to co-injection in HPLC, and
      were found to be matching with the impurities present in the sample. LC-MS was
      performed to identify the mass of these impurities. Based on their spectral data
      (IR, NMR, and Mass), these impurities were characterized as 2-benzyl-5-[(E)-2-(4
      hydroxyphenyl)ethenyl]benzene-1,3-diol [Impurity-B], 3-(benzyloxy)-5-[(E)-2-(4
      hydroxyphenyl)ethenyl]phenol [Impurity-C], 5-{(E)-2-[4
      (benzyloxy)phenyl]ethenyl}benzene-1,3-diol [Impurity-D). These compounds are not
      reported earlier as process-related impurities.

PMID- 24106668
TI  - Development and Validation of a Stability-Indicating RP-HPLC Method for the
      Determination of Process-Related Impurities and Degradation Products of
      Rabeprazole Sodium in Pharmaceutical Formulation.
AB  - The objective of the current study was to develop and validate a reversed-phase
      high-performance liquid chromatographic method for the quantitative determination
      of process-related impurities and degradation products of rabeprazole sodium in
      pharmaceutical formulation. Chromatographic separation was achieved on the Waters
      Symmetry Shield RP18 (250 mm * 4.6 mm) 5 MUm column with a mobile phase
      containing a gradient mixture of solvent A (mixture of 0.025 M KH2PO4 buffer and
      0.1% triethylamine in water, pH 6.4 and acetonitrile in the ratio of 90:10 v/v,
      respectively) and solvent B (mixture of acetonitrile and water in the ratio of
      90:10 v/v, respectively). The mobile phase was delivered at a flow rate of 1.0
      mL/min and with UV detection at 280 nm. Rabeprazole sodium was subjected to the
      stress conditions of oxidative, acid, base, hydrolytic, thermal, and photolytic
      degradation. Rabeprazole sodium was found to degrade significantly under acid
      hydrolysis, base hydrolysis, oxidative, and thermal degradation conditions. The
      degradation products were well-resolved from the main peak and its impurities,
      thus proving the stability-indicating power of the method. The mass balance was
      found to be in the range of 97.3-101.3% in all of the stressed conditions, thus
      proving the stability-indicating power of the method. The developed method was
      validated as per ICH guidelines with respect to specificity, linearity, limit of
      detection, limit of quantification, accuracy, precision, and robustness.

PMID- 24106669
TI  - Validated Stability-Indicating HPLC-DAD Method for the Simultaneous Determination
      of Diclofenac Sodium and Diflunisal in Their Combined Dosage Form.
AB  - A simple, rapid, and highly selective HPLC-DAD method was developed for the
      simultaneous determination of diclofenac sodium (DIC) and diflunisal (DIF) in
      pure form and in their combined formulation. Effective chromatographic separation
      was achieved using a Zorbax SB-C8 (4.6*250 mm, 5 MUm particle size) column with a
      mobile phase composed of 0.05 M phosphoric acid, acetonitrile, and methanol in
      the ratio of 40:48:12 (by volume). The mobile phase was pumped isocratically at a
      flow rate of 1 mL/min, and quantification of the analytes was based on measuring
      their peak areas at 228 nm. The retention times for diflunisal and diclofenac
      were about 7.9 and 9.5 min, respectively. The reliability and analytical
      performance of the proposed HPLC procedure were statistically validated with
      respect to system suitability, linearity, ranges, precision, accuracy,
      specificity, robustness, detection, and quantification limits. Calibration curves
      were linear in the ranges of 5-100 MUg/mL for both drugs with correlation
      coefficients >0.9998. The proposed method proved to be selective and stability
      indicating by the resolution of the two analytes from four of their related
      substances and potential impurities as well as from forced-degradation
      (hydrolysis, oxidation, photolysis, and dry heat) products. The validated HPLC
      method was successfully applied to the analysis of DIC and DIF in their combined
      dosage form (suppositories). The proposed method made use of the diode array
      detector (DAD) as a tool for peak identity and purity confirmation.

PMID- 24106670
TI  - Validation of a stability-indicating hydrophilic interaction liquid
      chromatographic method for the quantitative determination of vitamin k3
      (menadione sodium bisulfite) in injectable solution formulation.
AB  - A simple, specific, accurate, and stability-indicating method was developed and
      validated for the quantitative determination of menadione sodium bisulfite in the
      injectable solution formulation. The method is based on zwitterionic hydrophilic
      interaction liquid chromatography (ZIC-HILIC) coupled with a photodiode array
      detector. The desired separation was achieved on the ZIC-HILIC column (250 mm *
      4.6 mm, 5 MUm) at 25 degrees C temperature. The optimized mobile phase consisted
      of an isocratic solvent mixture of 200mM ammonium acetate (NH4AC) solution and
      acetonitrile (ACN) (20:80; v/v) pH-adjusted to 5.7 by glacial acetic acid. The
      mobile phase was fixed at 0.5 ml/min and the analytes were monitored at 261 nm
      using a photodiode array detector. The effects of the chromatographic conditions
      on the peak retention, peak USP tailing factor, and column efficiency were
      systematically optimized. Forced degradation experiments were carried out by
      exposing menadione sodium bisulfite standard and the injectable solution
      formulation to thermal, photolytic, oxidative, and acid-base hydrolytic stress
      conditions. The degradation products were well-resolved from the main peak and
      the excipients, thus proving that the method is a reliable, stability-indicating
      tool. The method was validated as per ICH and USP guidelines (USP34/NF29) and
      found to be adequate for the routine quantitative estimation of menadione sodium
      bisulfite in commercially available menadione sodium bisulfite injectable
      solution dosage forms.

PMID- 24106671
TI  - Pharmacological analysis of the rat femoral artery response to bradykinin.
AB  - Bradykinin (BK) plays an important role in different physiological processes
      including the general preservation and modulation of vascular systems. The
      present study was designed in order to examine the effect of BK on isolated rat
      femoral artery rings and to investigate the participation of intact endothelium,
      cyclooxygenase products, Ca(2+) channels, Na(+)/K(+)-ATPase, and B2 kinin
      receptors in BK-induced action. Circular artery segments were placed in organ
      baths. The endothelium was mechanically removed from some arteries. Concentration
      contraction curves for BK were obtained in the rings previously equilibrated at
      the basal tone. BK produced a concentration-dependent contraction, which was
      reduced by endothelial denudation. The BK-induced effect was almost completely
      inhibited by indomethacin (cyclooxygenase inhibitor) or OKY-046 (thromboxane A2
      synthase inhibitor). Nifedipine (Ca(2+) channel blocker), ouabain (Na(+)/K(+)
      ATPase inhibitor), or HOE-140 (selective B2 kinin receptor antagonist)
      significantly reduced the BK-evoked effect. In conclusion, it can be proposed
      that BK produces concentration- and endothelium-dependent contractions of the
      isolated rat femoral artery, which is for the most part a consequence of B2 kinin
      receptor activation. Cyclooxygenase contractile products, especially thromboxane
      A2, play a significant role in this course of action. The transduction mechanism
      involved in the process of BK-induced femoral artery contraction include the
      activation of voltage-gated Ca(2+) channels, and in a smaller extent Na(+)/K(+)
      ATPase as well.

PMID- 24106672
TI  - Nitric Oxide is a Potential Diagnostic Marker for Hepatocellular Carcinoma.
AB  - Hepatocellular carcinoma (HCC) is the fifth most common cancer in men and the
      seventh most common in women. This cancer varies widely in incidence throughout
      the world, with rising incidence in Egypt. HCC is considered the second most
      frequent cause of cancer incidence and mortality among men in Egypt. This study
      aimed to estimate the serum levels of nitric oxide (NO) and glutathione reductase
      in order to evaluate their role as oxidative status markers in HCC development
      and progression. For this purpose, serum levels of these parameters were assessed
      in 50 HCC patients, and 30 cirrhotic patients in addition to 15 healthy subjects
      as a control group. In the present study, glutathione reductase activity showed a
      significant increase in HCC as compared to the control group (P= 0.019). On the
      other hand, no significant difference was observed between the cirrhotic and HCC
      patients (P= 0.492). Serum NO was significantly higher in patients with HCC than
      in cirrhotic patients (P= 0.001) or the control group (P= 0.001), with a
      sensitivity of (74%) and specificity of (88.89%) at a cut-off level of 614.1
      MUmol/l. While AFP, alpha-fetoprotein, at a cutoff level of 200 ng/ml had a
      sensitivity of (52%), the specificity was (100%). Indeed, nitric oxide was high
      in 62.5% of AFP-negative HCC patients. In conclusion, glutathione reductase has
      no role in HCC diagnosis. However, nitric oxide is a potential diagnostic marker
      for HCC. The simultaneous determination of serum nitric oxide and AFP gave
      significant improvement in the detection of HCC patients compared to that of AFP
      alone.

PMID- 24106673
TI  - A Randomized, Crossover, Single-Dose Bioequivalence Study of Two Extended-Release
      Tablets of Donepezil 23 mg in Healthy Human Volunteers under Fasting and Fed
      States.
AB  - To assess the bioequivalence of two extended-release tablets of donepezil 23 mg,
      open label, randomized, single-dose, two-sequence, two-period crossover studies
      under fasting (n=74) and fed (n=94) conditions in healthy adult human volunteers
      were conducted. Subjects were randomized to either of the two treatment arms
      (test or reference) separated by a washout period of 28 days. Blood samples were
      collected up to 72 h post-dose and plasma samples were analyzed for donepezil
      using a validated LC-MS/MS method. Pharmacokinetic parameters were derived using
      a non-compartmental approach. Bioequivalence was evaluated in 69 subjects in the
      fasting study, and 71 subjects in the fed study. In the fasting study, the 90% CI
      of Cmax and AUC0-72 were 82.50-90.10 and 92.38-98.60, respectively. Corresponding
      values in the fed study were 91.82-98.05 and 97.27-100.27. Based on the results,
      the test product (donepezil) met the US regulatory criteria of bioequivalence
      relative to the reference product (Aricept((r))) under both fasting and fed
      conditions.

PMID- 24106674
TI  - Compounds from gum ammoniacum with acetylcholinesterase inhibitory activity.
AB  - The use of herbal medicinal preparations in dementia therapy has been studied
      based on experience from traditional medicine. A dichloromethane extract of gum
      ammoniacum, the gum-resin from Dorema ammoniacum D. Don had shown
      acetylcholinesterase (AChE) inhibitory activity in a previous study. The aim of
      this study was the isolation and characterization of the active compounds from
      this resin. The extract was investigated by a respective colorimetric microplate
      assay and the active zones were identified via TLC bioautography and isolated
      using several chromatographic techniques. The structures of the active components
      were characterized by one- and two-dimensional (1)H and (13)C NMR spectroscopy
      and mass spectrometry as (2'S,5'S)-2'-ethenyl-5'-(3-hy-droxy-6-methyl-4-oxohept-5
      en-2-yl)-7-methoxy-2'-methyl-4H-spiro[chromene-3,1'-cyclopentane]-2,4-dione (1),
      which is an analogue of doremone A and a new natural compound, and as (2'S,5'R)
      2'-ethenyl-5'-[(2R,4R)-4-hydroxy-6-methyl-3-oxohept-5-en-2-yl]-7-methoxy-2'
      methyl-4H-spiro[chromene-3,1'-cyclo-pentane]-2,4-dione (2 = doremone A), (4E,8E)
      1-(2,4-dihydroxyphenyl)-5,9,13-trimethyltetradeca-4,8,12-trien-1-one (3 =
      dshamirone), and 4,7-dihydroxy-3-[(2E,6E)-3,7,11-trimethyldodeca-2,6,10-trien-1
      yl]-2H-chromen-2-one (4 = am-moresinol). Dshamirone turned out to be the most
      active compound with an IC50 value for AChE inhibitory activity of 23.5 MUM,
      whereas the other substances showed weak activity. The concentrations of the
      analytes in the resin were determined by HPLC as 3.1%, 4.6%, 1.9%, and 9.9%,
      respectively.

PMID- 24106675
TI  - Quantification of Sesquiterpene Lactones in Asteraceae Plant Extracts: Evaluation
      of their Allergenic Potential.
AB  - Sesquiterpene lactones (SLs), mainly those with an activated exocyclic methylene
      group, are important allergens in Asteraceae (Compositae) plants. As a screening
      tool, the Compositae mix, consisting of five Asteraceae plant extracts with
      allergenic potential (feverfew, tansy, arnica, yarrow, and German chamomile) is
      part of several national patch test baseline series. However, the SL content of
      the Compositae mix may vary due to the source material. Therefore, a simple
      spectrophotometric method for the quantitative measurement of SLs with the alpha
      methylene-gamma-butyrolactone moiety was developed, giving the percentage of
      allergenic compounds in plant extracts. The method has been validated and five
      Asteraceae extracts, namely feverfew (Tanacetum parthenium L.), tansy (Tanacetum
      vulgare L.), arnica (Arnica montana L.), yarrow (Achillea millefolium L.), and
      German chamomile (Chamomilla recutita L. Rauschert) that have been used in
      routine patch test screening were evaluated. A good correlation could be found
      between the results obtained using the proposed spectrophotometric method and the
      corresponding clinical results. Thus, the introduced method is a valuable tool
      for evaluating the allergenic potential and for the simple and efficient quality
      control of plant extracts with allergenic potential.

PMID- 24106676
TI  - Poly-Ingredient Formulation Bresol((r)) Ameliorates Experimental Chronic
      Obstructive Pulmonary Disease (COPD) in Rats.
AB  - In the present study, the protective effect of Bresol((r)) - a polyherbal
      formulation - was evaluated in an experimental model of cigarette smoke (CS)
      induced COPD in rats. Ten minutes daily exposure to CS for 7 weeks caused
      significant elevation of TNF-alpha (p<0.01) and total protein (p<0.01) in the
      bronchoalveolar lavage fluid (BALF) of positive untreated control animals,
      indicating ongoing inflammatory process in the lungs. Further, histopathological
      findings have confirmed the presence of pathological lesions in the trachea and
      lungs. Five weeks of post-treatment with Bresol((r)) (250 and 500 mg/kg, p.o.)
      showed significant and dose-dependent anti-inflammatory effects against CS
      induced lung abnormalities by maintaining the TNF-alpha and total protein levels
      within the normal range. Additionally, Bresol((r))-treated animals showed normal
      cyto-architecture of the trachea and lungs. In conclusion, Bresol((r)) showed
      dose-dependent protection against CS-induced lung and tracheal injury in rats,
      which further indicates, Bresol((r)) is a useful healing agent, may help to
      decelerate the progression of COPD, and reduce the exacerbations in patients.

PMID- 24106677
TI  - Intranasal delivery of chitosan nanoparticles for migraine therapy.
AB  - OBJECTIVE: The objective of the research was to formulate and evaluate
      sumatriptan succinate-loaded chitosan nanoparticles for migraine therapy in order
      to improve its therapeutic effect and reduce dosing frequency. MATERIAL AND
      METHODS: The Taguchi method design of experiments (L9 orthogonal array) was
      applied to obtain the optimized formulation. The sumatriptan succinate-loaded
      chitosan nanoparticles (CNPs) were prepared by ionic gelation of chitosan with
      tripolyphosphate anions (TPP) and Tween 80 as surfactant. RESULTS: The CNPs had a
      mean size of 306.8 +/- 3.9 nm, a zeta potential of +28.79 mV, and entrapment
      efficiency of 75.4 +/- 1.1%. The in vitro drug release of chitosan nanoparticles
      was evaluated in phosphate buffer saline pH 5.5 using goat nasal mucosa and found
      to be 76.7 +/- 1.3% within 28 hours. DISCUSSION: The release of the drug from the
      nanoparticles was anomalous, showing non-Fickian diffusion indicating that drug
      release is controlled by more than one process i.e. the superposition of both
      phenomena, a diffusion-controlled as well as a swelling-controlled release. This
      is clearly due to the characteristics of chitosan which easily dissolves at low
      pH, thus a nasal pH range of 5.5 +/- 0.5 supports it very well. The mechanism of
      pH-sensitive swelling involves protonation of the amine groups of chitosan at low
      pH. This protonation leads to chain repulsion, diffusion of protons and counter
      ions together with water inside the gel, and the dissociation of secondary
      interactions. CONCLUSION: The results suggest that sumatriptan succinate-loaded
      chitosan nanoparticles are the most suitable mode of drug delivery for promising
      therapeutic action.

PMID- 24106678
TI  - Evidence of Polymorphism on the Antitrypanosomal Naphthoquinone (4E)-2-(1H
      Pyrazol-3-ylamino)-4-(1H-pyrazol-3-ylimino)naphthalen-1(4H)-one.
AB  - The aim of this study was to characterize the solid state properties of (4E)-2
      (1H-pyrazol-3-ylamino)-4-(1H-pyrazol-3-ylimino)naphthalen-1(4H)-one (BiPNQ), a
      compound with a significant inhibitory activity against Trypanosoma cruzi, the
      etiological agent of Chagas disease (American trypanosomiasis). Methods used
      included Differential Scanning Calorimetry (DSC), Thermogravimetry (TG), Fourier
      Transform Infrared Spectroscopy (FTIR), Powder X-Ray Diffraction (PXRD), Hot
      Stage, and Confocal Microscopy. Two BiPNQ samples were obtained by
      crystallization from absolute methanol and 2-propanol-water that exhibited
      different thermal behaviours, PXRD patterns, and FTIR spectra, indicating the
      existence of an anhydrous form (BiPNQ-I) and a solvate (BIPNQ-s), which on
      heating desolvated leading to the anhydrous modification BiPNQ-I. It was
      determined that FTIR, DSC, and PXRD are useful techniques for the
      characterization and identification of the crystalline modifications of BiPNQ.

PMID- 24106679
TI  - Rivastigmine-loaded L-lactide-depsipeptide polymeric nanoparticles: decisive
      formulation variable optimization.
AB  - The main aim of the investigation was to explore a novel L-lactide-depsipeptide
      copolymer for the development of rivastigmine-loaded polymeric nanoparticles. L
      lactide-depsipeptide synthesis was based on the ring opening polymerization
      reaction of L-lactide with the cyclodepsipeptide, cyclo(Glc-Leu), using tin 2
      ethyl hexanoate as an initiator. Rivastigmine-loaded nanoparticles were prepared
      by the single emulsion-solvent evaporation technique. The influence of various
      critical formulation variables like sonication time, amount of polymer, amount of
      drug, stabilizer concentration, drug-to-polymer ratio, and organic-to-aqueous
      phase ratio on particle size and entrapment efficiency was studied. The optimized
      formulation having a particle size of 142.2 +/- 21.3 nm with an entrapment
      efficiency of 60.72 +/- 3.72% was obtained. Increased rivastigmine entrapment
      within the polymer matrix was obtained with a relatively low organic-to-aqueous
      phase ratio and high drug-to-polymer ratio. A decrease in the average size of the
      nanoparticles was observed with a decrease in the amount of polymer added and an
      increase in the sonication time. Prolonged sonication time, however, decreased
      rivastigmine entrapment. From the different lyoprotectant tested, only trehalose
      was found to prevent nanoparticle aggregation upon application of the freeze-thaw
      cycle. Drug incorporation into the polymeric matrix was confirmed by the DSC and
      XRD study. The spherical nature of the nanoparticles was confirmed by the SEM
      study. The in vitro drug release study showed the sustained release of more than
      90% of the drug up to 72 h. Thus, L-lactide-depsipeptide can be used as an
      efficient carrier for the nanoparticle preparation of rivastigmine.

PMID- 24106681
TI  - Prospective multicenter phase II clinical trial of FOLFIRI chemotherapy as a
      neoadjuvant treatment for colorectal cancer with multiple liver metastases.
AB  - PURPOSE: This study evaluated the efficacy of neoadjuvant chemotherapy combining
      5-flurouracil/folinic acid with irinotecan (FOLFIRI) in colorectal multiple liver
      metastases regardless of resectability. METHODS: Forty-four patients with
      multiple (at least two) colorectal liver metastases were enrolled at seven
      tertiary referral hospitals between May 2007 and September 2010. All patients
      received the FOLFIRI chemotherapeutic regimen. Response to chemotherapy was
      assessed after three cycles (6 weeks) and once more after six cycles (12 weeks)
      of treatment. RESULTS: Objective response was noted in 27 patients (61.4%) and 4
      patients (9.1%) had progressive disease. Of 44 patients, 10 patients (22.7%)
      underwent curative surgery (R0 resection) and 34 patients did not receive R0
      resection. Grades 3 to 4 hematological toxicity was noted in 12 patients (27.3%)
      and grades 3 to 4 nonhematologic toxicity was identified in 5 patients (11.4%).
      CONCLUSION: FOLFIRI chemotherapy as a neoadjuvant chemotherapy for multiple
      colorectal liver metastases regardless of resectability demonstrated the
      possibility of R0 resection, high rate of objective response, and tolerable
      toxicities in this study.

PMID- 24106680
TI  - Effect of laparoscopic cholecystectomy techniques on postoperative pain: a
      prospective randomized study.
AB  - PURPOSE: Minimally invasive surgical technics have benefits such as decreased
      pain, reduced surgical trauma, and increased potential to perform as day case
      surgery, and cost benefit. The primary aim of this prospective, randomized,
      controlled study was to compare the effects of single incision laparoscopic
      cholecystectomy (SILC) and conventional laparoscopic cholecystectomy (CLC)
      procedures regarding postoperative pain. METHODS: Ninety adult patients
      undergoing elective laparoscopic cholecystectomy were included in the study.
      Patients were randomized to either SILC or CLC. Patient characteristics,
      postoperative abdominal and shoulder pain scores, rescue analgesic use, and
      intraoperative and early postoperative complications were recorded. RESULTS: A
      total of 83 patients completed the study. Patient characteristics, postoperative
      abdominal and shoulder pain scores and rescue analgesic requirement were similar
      between each group except with the lower abdominal pain score in CLC group at
      30th minute (P = 0.04). Wound infection was seen in 1 patient in each group.
      Nausea occurred in 13 of 43 patients (30%) in the SILC group and 8 of 40 patients
      (20%) in the CLC group (P > 0.05). Despite ondansetron treatment, 6 patients in
      SILC group and 7 patients in CLC group vomited (P > 0.05). CONCLUSION: In
      conclusion, in patients undergoing laparoscopic surgery, SILC or CLC techniques
      does not influence the postoperative pain and analgesic medication requirements.
      Our results also suggest that all laparoscopy patients suffer moderate and/or
      severe abdominal pain and nearly half of these patients also suffer from some
      form of shoulder pain.

PMID- 24106682
TI  - MicroRNA profiling of tacrolimus-stimulated Jurkat human T lympocytes.
AB  - PURPOSE: This study investigated the Jurkat T cell line expresses cytotoxicity
      when treated with different concentrations of FK506, and analyzed the expression
      pattern of microRNA when stimulated by FK506 using the microRNAs microarray, as
      well as the expression pattern of a gene that is related to the differentiation,
      activation and proliferation of T cells after being affected by the change of
      microRNAs. METHODS: To investigate the effects of FK506 on microRNA expression,
      we purified total RNA of Jurkat cells treated with 20 uM FK506 for 72 hours and
      used to analyze microRNA profiling by using Agilent's chip. RESULTS: These
      results demonstrated that treatment with FK506 markedly induced the down
      regulation of 20 microRNAs as well as the up-regulation of 20 microRNAs in a time
      dependent manner. The genes that down-regulated by FK506 include let-7a(*), miR
      20a(*), and miR-487a. Otherwise miR-202, miR-485-5p, and miR-518c(*) are
      gradually up-regulated in expression. Sanger Institute and DAVIDs bioinformatics
      indicated that microRNAs regulated the several transcriptomes including nuclear
      factor of activated T cell-related, T cell receptor/interleukin-2 signaling, and
      Ca(2+)-calmodulin-dependent phosphatase calcineurin pathways. CONCLUSION: As a
      result of treating FK506 to a Jurkat cell line and running the microRNA
      microarray, it was found that FK506 not only took part in the suppression of T
      cell proliferation/activation by inhibiting calcineurin in Jurkat apoptosis, but
      also affected the microRNAs that are involved in the regulation of various signal
      transduction pathways.

PMID- 24106683
TI  - The cutoff value of saphenous vein diameter to predict reflux.
AB  - PURPOSE: Increased saphenous vein diameter is a common consequence of saphenous
      vein reflux. Until now, there have been no reports about the correlation between
      diameter and reflux of saphenous vein in Korea. The aim of this study was to
      investigate the correlation between saphenous vein reflux and diameter changes.
      METHODS: From April 2009 to August 2012, 777 patients were sent to the vascular
      laboratory for evaluation of venous reflux. The diameter of the saphenous vein
      was measured with B-mode imaging, and reflux was quantified based on valve
      closure time using Doppler spectral tracings. Receiver operating characteristics
      curve analysis was applied to determine the best saphenous vein diameter cutoff
      for predicting reflux. RESULTS: The mean diameters of normal great saphenous vein
      (GSV) and refluxed GSV were 5.0 +/- 2.4 mm and 6.4 +/- 2.0 mm, respectively. The
      mean diameters of normal small saphenous vein (SSV) and refluxed SSV were 3.1 +/-
      1.3 mm and 5.2 +/- 2.7 mm, respectively. The diameter differences between the
      normal and refluxed GSV and SSV were 1.4 mm and 2.1 mm, respectively, and these
      differences were statistically significant (P < 0.0001). A GSV threshold diameter
      of 5.05 mm had the best positive predictive value for reflux. The sensitivity and
      specificity at 5.05 mm were 76% and 60%, respectively. The best SSV diameter for
      predicting reflux was 3.55 mm. The sensitivity and specificity at 3.55 mm were
      87% and 71%, respectively. CONCLUSION: GSV diameter of >=5.05 mm had the best
      positive predictive value for pathologic reflux. For pathologic reflux of SSV,
      the best cutoff diameter was 3.55 mm.

PMID- 24106684
TI  - Inguinal hernia developed after radical retropubic surgery for prostate cancer.
AB  - PURPOSE: In this retrospective study, we aimed to compare the clinical
      characteristics of inguinal hernia developed after radical retropubic surgery for
      prostate cancer to the hernia without previous radical prostatectomy. METHODS:
      Twenty-three patients (group A) who had radical retropubic surgery for prostate
      cancer underwent laparoscopic or open tension-free inguinal hernia repair from
      March 2007 to February 2011. Nine hundred and forty patients (group B) without
      previous radical retropubic surgery received laparoscopic or tension-free open
      hernia operation. RESULTS: Group A was older than group B (mean +/- standard
      deviation, 69.6 +/- 7.2 vs. 54.1 +/- 16.1; P < 0.001). Right side (73.9%) and
      indirect type (91.3%) in group A were more prevalent than in group B (51.5% and
      69.4%, respectively) with statistic significance (P = 0.020 and P = 0.023). The
      rate of laparoscopic surgery in group B (n = 862, 91.7%) was higher than in group
      A (n = 14, 64.3%, P < 0.001). In comparing perioperative variables between the
      two groups, operative time (49.4 +/- 23.5 minutes) and hospital stay (1.9 +/- 0.7
      days) in group A were longer than in group B (38.9 +/- 16.9, 1.1 +/- 0.2; P =
      0.046 and P < 0.001, respectively) and pain score at 7 days in group A was higher
      than in group B (3.1 +/- 0.7 vs. 2.3 +/- 1.0, P < 0.001). Postoperative
      recurrence rate was not significantly different between the two groups.
      CONCLUSION: Inguinal hernia following radical retropubic surgery for prostate
      cancer was predominantly right side and indirect type with statistic significance
      compared to hernias without previous radical prostatectomy.

PMID- 24106685
TI  - Application of negative pressure wound therapy in patients with wound dehiscence
      after abdominal open surgery: a single center experience.
AB  - PURPOSE: Since the 1990's, negative pressure wound therapy (NPWT) has been used
      to treat soft tissue defects, burn wounds, and to achieve skin graft fixation. In
      the field of abdominal surgery, the application of NPWT is increasing in cases
      with an open abdominal wound requiring temporary wound closure and a second look
      operation. In the present study, the authors analyzed patients that underwent
      NPWT for postoperative wound dehiscence. METHODS: The computerized records of
      patients that had undergone an abdominal operation from November 2009 to May 2012
      were retrospectively analyzed. RESULTS: The number of total enrolled patients was
      50, and 30 patients (60%) underwent an emergency operation. Diagnoses were as
      follows: panperitonitis or intra-abdominal abscess (24 cases, 48%), intestinal
      obstruction (10 cases, 20%), cancer (7 cases, 14%), mesentery ischemia (3 cases,
      6%), and hemoperitoneum (1 case, 2%). NPWT was applied at a mean of 12.9 +/- 8.2
      days after surgery and mean NPWT duration was 17.9 days (2 to 96 days). The 11
      patients (22%) with unsuccessful wound closure had a deeper and more complex
      wound than the other 39 patients (78%) (90.9% vs. 38.5%, P = 0.005). There were
      two complication cases (4%) due to delayed wound healing. CONCLUSION: Most
      patients recovered well due to granulation formation and suturing. NPWT was found
      to be convenient and safe, but a prospective comparative study is needed to
      confirm the usefulness of NPWT in patients whose wounds are dehisced.

PMID- 24106686
TI  - A preliminary study: aspirin discontinuation before elective operations; when is
      the optimal timing?
AB  - PURPOSE: To evaluate the optimum timing of aspirin cessation before noncardiac
      surgeries. We have conducted a pilot study to minimize the aspirin cessation time
      before various surgeries. METHODS: Eighty patients who were taking regular
      aspirin for secondary prevention undergoing elective surgical operations were
      enrolled in the study. We separated the patients into two groups. The control
      group had 35 patients who stopped aspirin intake 10 days before surgery. The
      study group had 45 patients who stopped their aspirin intake and underwent
      surgery one day after arachidonic acid aggregation tests were within normal
      limits. Bleeding, blood loss, and transfusion requirements were assessed
      perioperatively. RESULTS: The mean time between aspirin cessation and aspirin
      nonresponsiveness were found to be 4.2 days with a median value of 4 days. In
      addition, the mean time between aspirin cessation and operation day were found to
      be 5.5 days with a median value of 5 days. No perioperative bleeding,
      thromboembolic or cardiovascular complications were encountered. CONCLUSION:
      Reducing time of aspirin cessation from 7-10 days to 4-5 days is a possibility
      for patients using aspirin for secondary prevention without increased
      perioperative complications.

PMID- 24106687
TI  - Xanthogranulomatous cholecystits in 2-month-old infant.
AB  - Xanthogranulomatous cholecystitis (XGC) is a rare form of chronic cholecystitis
      that is accompanied by xanthomatous histiocytes and chronic inflammation. A 2
      month-old boy presented with a right upper abdominal palpable mass.
      Cholecystectomy with liver wedge resection was done, under the impression that
      the mass might be a hepatic tumor or liver abscess. Pathologic examination showed
      XGC with abscess formation. Most cases of XGC were observed in adult and only a
      few cases were reported in children. We describe a very rare case of XGC in
      infancy. 

PMID- 24106688
TI  - Preduodenal portal vein: a 3-case series demonstrating varied presentations in
      infants.
AB  - Preduodenal portal vein, a rare anomaly, could be found in any age groups. In
      pediatrics it may present with a duodenal obstruction by itself or other
      coexisting anomalies; however it usually present with an asymptomatic or
      incidental findings during other surgery in adults. This anomaly has a clinical
      importance due to the possibility of accidental damage to portal vein. In
      addition to describing a series of 3 cases with different manifestation in
      infants, discuss about this anomaly with a review of relevant literature. 

PMID- 24106690
TI  - Somatostatin receptor-based molecular imaging and therapy for neuroendocrine
      tumors.
AB  - Neuroendocrine tumors (NETs) are tumors originated from neuroendocrine cells in
      the body. The localization and the detection of the extent of NETs are important
      for diagnosis and treatment, which should be individualized according to the
      tumor type, burden, and symptoms. Molecular imaging of NETs with high sensitivity
      and specificity is achieved by nuclear medicine method using single photon
      emitting and positron-emitting radiopharmaceuticals. Somatostatin receptor
      imaging (SRI) using SPECT or PET as a whole-body imaging technique has become a
      crucial part of the management of NETs. The radiotherapy with somatostatin
      analogues labeled with therapeutic beta emitters, such as lutetium-177 or yttrium
      90, has been proved to be an option of therapy for patients with unresectable and
      metastasized NETs. Molecular imaging can deliver an important message to improve
      the outcome for patients with NETs by earlier diagnosis, better choice of the
      therapeutic method, and evaluation of the therapeutic response. 

PMID- 24106691
TI  - Leflunomide as a corticosteroid-sparing agent in giant cell arteritis and
      polymyalgia rheumatica: a case series.
AB  - OBJECTIVES: Giant cell arteritis (GCA) and polymyalgia rheumatica (PMR) affect
      individuals older than 50 years of age and corticosteroids are the mainstay of
      treatment. The aim of our study was to explore the role of leflunomide as a
      corticosteroid-sparing agent in GCA and PMR patients. METHODS: Patients with
      difficult-to-treat GCA and PMR were retrospectively identified in the period from
      2010 to 2013. The doses of corticosteroids and CRP values were noted before,
      after three months, and at the end of the treatment with leflunomide (for
      patients continuing treatment, censoring date was January 1, 2013). RESULTS:
      Twenty-three patients were identified (12 with PMR and 11 with GCA). A reduction
      of 6 mg/dL (CI 95% -10.9-34.2, P = 0.05) in CRP and 3.7 mg (CI 95% 0.5-7.0, P =
      0.03) in prednisolone dose was observed in the PMR group. In GCA patients, the
      reduction was 12.4 mg/dL (CI 95% 0.7-25.5, P = 0.06) in CRP and 6.6 mg (CI 95%
      2.8-10.3, P < 0.01) in prednisolone dose. CONCLUSION: Leflunomide seems to be
      effective as a corticosteroid-sparing agent in patients with difficult-to-treat
      GCA and PMR. Randomized controlled trials are warranted in order to confirm the
      usefulness of leflunomide in the therapy of GCA/PMR.

PMID- 24106689
TI  - Transcriptional regulation by Ferric Uptake Regulator (Fur) in pathogenic
      bacteria.
AB  - In the ancient anaerobic environment, ferrous iron (Fe(2+)) was one of the first
      metal cofactors. Oxygenation of the ancient world challenged bacteria to acquire
      the insoluble ferric iron (Fe(3+)) and later to defend against reactive oxygen
      species (ROS) generated by the Fenton chemistry. To acquire Fe(3+), bacteria
      produce low-molecular weight compounds, known as siderophores, which have
      extremely high affinity for Fe(3+). However, during infection the host restricts
      iron from pathogens by producing iron- and siderophore-chelating proteins, by
      exporting iron from intracellular pathogen-containing compartments, and by
      limiting absorption of dietary iron. Ferric Uptake Regulator (Fur) is a
      transcription factor which utilizes Fe(2+) as a corepressor and represses
      siderophore synthesis in pathogens. Fur, directly or indirectly, controls
      expression of enzymes that protect against ROS damage. Thus, the challenges of
      iron homeostasis and defense against ROS are addressed via Fur. Although the role
      of Fur as a repressor is well-documented, emerging evidence demonstrates that Fur
      can function as an activator. Fur activation can occur through three distinct
      mechanisms (1) indirectly via small RNAs, (2) binding at cis regulatory elements
      that enhance recruitment of the RNA polymerase holoenzyme (RNAP), and (3)
      functioning as an antirepressor by removing or blocking DNA binding of a
      repressor of transcription. In addition, Fur homologs control defense against
      peroxide stress (PerR) and control uptake of other metals such as zinc (Zur) and
      manganese (Mur) in pathogenic bacteria. Fur family members are important for
      virulence within bacterial pathogens since mutants of fur, perR, or zur exhibit
      reduced virulence within numerous animal and plant models of infection. This
      review focuses on the breadth of Fur regulation in pathogenic bacteria. 

PMID- 24106693
TI  - Cloud infrastructures for in silico drug discovery: economic and practical
      aspects.
AB  - Cloud computing opens new perspectives for small-medium biotechnology
      laboratories that need to perform bioinformatics analysis in a flexible and
      effective way. This seems particularly true for hybrid clouds that couple the
      scalability offered by general-purpose public clouds with the greater control and
      ad hoc customizations supplied by the private ones. A hybrid cloud broker, acting
      as an intermediary between users and public providers, can support customers in
      the selection of the most suitable offers, optionally adding the provisioning of
      dedicated services with higher levels of quality. This paper analyses some
      economic and practical aspects of exploiting cloud computing in a real research
      scenario for the in silico drug discovery in terms of requirements, costs, and
      computational load based on the number of expected users. In particular, our work
      is aimed at supporting both the researchers and the cloud broker delivering an
      IaaS cloud infrastructure for biotechnology laboratories exposing different
      levels of nonfunctional requirements. 

PMID- 24106692
TI  - Antioxidant properties of Brazilian tropical fruits by correlation between
      different assays.
AB  - Four different assays (the Folin-Ciocalteu, DPPH, enzymatic method, and
      inhibitory activity on lipid peroxidation) based on radically different
      physicochemical principles and normally used to determine the antioxidant
      activity of food have been confronted and utilized to investigate the antioxidant
      activity of fruits originated from Brazil, with particular attention to more
      exotic and less-studied species (jurubeba, Solanum paniculatum; pequi, Caryocar
      brasiliense; pitaya, Hylocereus undatus; siriguela, Spondias purpurea; umbu,
      Spondias tuberosa) in order to (i) verify the correlations between results
      obtained by the different assays, with the final purpose to obtain more reliable
      results avoiding possible measuring-method linked mistakes and (ii) individuate
      the more active fruit species. As expected, the different methods give different
      responses, depending on the specific assay reaction. Anyhow all results indicate
      high antioxidant properties for siriguela and jurubeba and poor values for
      pitaya, umbu, and pequi. Considering that no marked difference of ascorbic acid
      content has been detected among the different fruits, experimental data suggest
      that antioxidant activities of the investigated Brazilian fruits are poorly
      correlated with this molecule, principally depending on their total polyphenolic
      content. 

PMID- 24106694
TI  - Biomarker selection and classification of "-omics" data using a two-step bayes
      classification framework.
AB  - Identification of suitable biomarkers for accurate prediction of phenotypic
      outcomes is a goal for personalized medicine. However, current machine learning
      approaches are either too complex or perform poorly. Here, a novel two-step
      machine-learning framework is presented to address this need. First, a Naive
      Bayes estimator is used to rank features from which the top-ranked will most
      likely contain the most informative features for prediction of the underlying
      biological classes. The top-ranked features are then used in a Hidden Naive Bayes
      classifier to construct a classification prediction model from these filtered
      attributes. In order to obtain the minimum set of the most informative
      biomarkers, the bottom-ranked features are successively removed from the Naive
      Bayes-filtered feature list one at a time, and the classification accuracy of the
      Hidden Naive Bayes classifier is checked for each pruned feature set. The
      performance of the proposed two-step Bayes classification framework was tested on
      different types of -omics datasets including gene expression microarray, single
      nucleotide polymorphism microarray (SNParray), and surface-enhanced laser
      desorption/ionization time-of-flight (SELDI-TOF) proteomic data. The proposed two
      step Bayes classification framework was equal to and, in some cases, outperformed
      other classification methods in terms of prediction accuracy, minimum number of
      classification markers, and computational time. 

PMID- 24106695
TI  - Recovery of stored aerobic granular sludge and its contaminants removal
      efficiency under different operation conditions.
AB  - The quick recovery process of contaminants removal of aerobic granular sludge
      (AGS) is complex, and the influencing factors are still not clear. The effects of
      dissolved oxygen (DO, air intensive aeration rate), organic loading rate (OLR),
      and C/N on contaminants removal characteristics of AGS and subsequently long-term
      operation of AGS bioreactor were investigated in this study. DO had a major
      impact on the recovery of AGS. The granules reactivated at air intensive aeration
      rate of 100 L/h achieved better settling property and contaminants removal
      efficiency. Moreover, protein content in extracellular polymeric substance (EPS)
      was almost unchanged, which demonstrated that an aeration rate of 100 L/h was
      more suitable for maintaining the biomass and the structure of AGS. Higher OLR
      caused polysaccharides content increase in EPS, and unstable C/N resulted in the
      overgrowth of filamentous bacteria, which presented worse NH4 (+)-N and PO4 (3-)
      P removal. Correspondingly, quick recovery of contaminants removal was
      accomplished in 12 days at the optimized operation conditions of aeration rate
      100 L/h, OLR 4 g/L.d, and C/N 100 : 10, with COD, NH4 (+)-N, and PO4 (3-)-P
      removal efficiencies of 87.2%, 86.9%, and 86.5%, respectively. The renovation of
      AGS could be successfully utilized as the seed sludge for the rapid start-up of
      AGS bioreactor. 

PMID- 24106696
TI  - In silico determination and validation of baumannii acinetobactin utilization a
      structure and ligand binding site.
AB  - Acinetobacter baumannii is a deadly nosocomial pathogen. Iron is an essential
      element for the pathogen. Under iron-restricted conditions, the bacterium
      expresses iron-regulated outer membrane proteins (IROMPs). Baumannii
      acinetobactin utilization (BauA) is the most important member of IROMPs in A.
      baumannii. Determination of its tertiary structure could help deduction of its
      functions and its interactions with ligands. The present study unveils BauA 3D
      structure via in silico approaches. Apart from ab initio, other rational methods
      such as homology modeling and threading were invoked to achieve the purpose. For
      homology modeling, BLAST was run on the sequence in order to find the best
      template. The template was then served to model the 3D structure. All the models
      built were evaluated qualitatively. The best model predicted by LOMETS was
      selected for analyses. Refinement of 3D structure as well as determination of its
      clefts and ligand binding sites was carried out on the structure. In contrast to
      the typical trimeric arrangement found in porins, BauA is monomeric. The barrel
      is formed by 22 antiparallel transmembrane beta -strands. There are short
      periplasmic turns and longer surface-located loops. An N-terminal domain referred
      to either as the cork, the plug, or the hatch domain occludes the beta -barrel. 

PMID- 24106697
TI  - Potential utility of sodium selenate as an adjunct to metformin in treating type
      II diabetes mellitus in rats: a perspective on protein tyrosine phosphatase.
AB  - Metformin is widely regarded as the standard first-line antidiabetic agent, in
      terms of efficacy and safety profiles. However, in most patients with type II
      diabetes mellitus (T2DM), it was found that metformin alone is not enough to
      adequately control hyperglycemia. Thus, we designed this study with the aim to
      investigate the effect of sodium selenate, a protein tyrosine phosphatase (PTP)
      inhibitor, individually and as an adjunct to metformin, on a rat model that
      simulates the metabolic characteristics of human T2DM. T2DM model was achieved by
      feeding the rats with high-fat, high-fructose diet (HFFD) for 8 weeks followed by
      a low dose of streptozotocin (STZ) (35 mg/kg/day, i.p.). Changes in serum
      glucose, insulin, adiponectin, homeostasis model assessment of insulin resistance
      (HOMA-IR) index, and the lipid profile were assessed. In addition, the level of
      reduced glutathione (GSH) and the activity of PTP were determined in the liver.
      Results showed that the addition of sodium selenate to metformin was able to
      restore hepatic GSH back to normal levels. Also, this combination therapy
      corrected the altered serum total cholesterol (TC), triglycerides (TG), and
      adiponectin levels. In conclusion, additive therapeutic effect was recorded when
      sodium selenate was used as an adjunct to metformin. 

PMID- 24106698
TI  - Improved properties of poly(3-hydroxybutyrate-co-3-hydroxyvalerate) produced by
      Comamonas sp. EB172 utilizing volatile fatty acids by regulating the nitrogen
      source.
AB  - This study presents the effect of carbon to nitrogen ratio (C/N) (mol/mol) on the
      cell growth and poly(3-hydroxybutyrate-co-3-hydroxyvalerate) accumulation by
      Comamonas sp. EB172 in 2 L fermenters using volatile fatty acids (VFA) as the
      carbon source. This VFA was supplemented with ammonium sulphate and yeast extract
      in the feeding solution to achieve C/N (mol/mol) 5, 15, 25, and 34.4,
      respectively. By extrapolating the C/N and the source of nitrogen, the properties
      of the polymers can be regulated. The number average molecular weight (M n ) of
      P(3HB-co-3HV) copolymer reached the highest at 838 * 10(3) Da with polydispersity
      index (PDI) value of 1.8, when the culture broth was supplemented with yeast
      extract (C/N 34.4). Tensile strength and Young's modulus of the copolymer
      containing 6-8 mol% 3HV were in the ranges of 13-14.4 MPa and 0.26-0.34 GPa,
      respectively, comparable to those of polyethylene (PE). Thus, Comamonas sp. EB172
      has shown promising bacterial isolates producing polyhydroxyalkanoates from
      renewable carbon materials. 

PMID- 24106699
TI  - Role of the promoter polymorphism IL-6 -174G/C in dermatomyositis and systemic
      lupus erythematosus.
AB  - The promoter polymorphism -174G/C within the interleukin-6 gene (IL-6) has been
      reported to have a functional importance through the modulation of IL-6 gene
      expression in vitro and in vivo. IL-6 is thought to play an important role in
      autoimmune diseases and the effect of its receptor inhibitor-tocilizumab-has been
      recently studied. The aim of this case-control study was to investigate the
      association between the interleukin-6 -174G/C single nucleotide polymorphism and
      the susceptibility to dermatomyositis (DM) and systemic lupus erythematosus (SLE)
      in Bulgarian patients. Altogether, 87 patients-52 with SLE and 35 with DM-as well
      as 80 unrelated healthy controls were included in this study. All of them were
      analyzed by restriction fragment length polymorphism analysis (RFLP). The GG
      genotype and the G allele appeared to be associated with SLE, especially in
      women. None of the genotypes showed an association with DM. However, the G allele
      appeared to be associated with muscle weakness and it is a risk factor for
      elevated muscle enzymes. Our results indicate that IL-6 -174G/C polymorphism
      might be associated with the susceptibility to SLE especially in women. Although
      it is not associated with DM, it seems that IL-6 -174G/C polymorphism could
      modulate some clinical features in the autoimmune myopathies. 

PMID- 24106700
TI  - Effect of supracervical apposition and spontaneous labour on apoptosis and matrix
      metalloproteinases in human fetal membranes.
AB  - BACKGROUND: Apoptosis and matrix metalloproteinase (MMP-9) are capable of
      hydrolysing components of the extracellular matrix and weakening the fetal
      membranes which leads to eventual rupture, a key process of human parturition.
      The aim of this study was to determine the effect of supracervical apposition and
      spontaneous labour on apoptosis and MMP-9 in human fetal membranes at term.
      METHODS: Fetal membranes were obtained from term non-labouring supracervical site
      (SCS) and compared to (i) a paired distal site (DS) or (ii) site of rupture (SOR)
      after spontaneous labour onset. RESULTS: The expression of the proapoptotic
      markers Bax, Smac, Fas, FasL, caspase-3, and PARP, was significantly higher in
      the non-labouring SCS chorion compared to paired DS. Bax, Smac, FasL, caspase-3,
      and PARP staining was higher in the non-labouring SCS fetal membranes than that
      in the post-labour SOR. MMP-9 expression and activity were higher in the post
      labour SOR fetal membranes compared to non-labouring SCS fetal membranes.
      CONCLUSION: Components of the apoptotic signalling pathways and MMP-9 may play a
      role in rupture and labour. Non-labouring SCS fetal membranes display altered
      morphology and altered apoptotic biochemical characteristics in preparation for
      labour, while the laboured SOR displays unique MMP characteristics.

PMID- 24106702
TI  - Phylogenetic relationships of Pseudorasbora, Pseudopungtungia, and Pungtungia
      (Teleostei; Cypriniformes; Gobioninae) inferred from multiple nuclear gene
      sequences.
AB  - Gobionine species belonging to the genera Pseudorasbora, Pseudopungtungia, and
      Pungtungia (Teleostei; Cypriniformes; Cyprinidae) have been heavily studied
      because of problems on taxonomy, threats of extinction, invasion, and human
      health. Nucleotide sequences of three nuclear genes, that is, recombination
      activating protein gene 1 (rag1), recombination activating gene 2 (rag2), and
      early growth response 1 gene (egr1), from Pseudorasbora, Pseudopungtungia, and
      Pungtungia species residing in China, Japan, and Korea, were analyzed to
      elucidate their intergeneric and interspecific phylogenetic relationships. In the
      phylogenetic tree inferred from their multiple gene sequences, Pseudorasbora,
      Pseudopungtungia and Pungtungia species ramified into three phylogenetically
      distinct clades; the "tenuicorpa" clade composed of Pseudopungtungia tenuicorpa,
      the "parva" clade composed of all Pseudorasbora species/subspecies, and the
      "herzi" clade composed of Pseudopungtungia nigra, and Pungtungia herzi. The genus
      Pseudorasbora was recovered as monophyletic, while the genus Pseudopungtungia was
      recovered as polyphyletic. Our phylogenetic result implies the unstable taxonomic
      status of the genus Pseudopungtungia. 

PMID- 24106701
TI  - A broader view: microbial enzymes and their relevance in industries, medicine,
      and beyond.
AB  - Enzymes are the large biomolecules that are required for the numerous chemical
      interconversions that sustain life. They accelerate all the metabolic processes
      in the body and carry out a specific task. Enzymes are highly efficient, which
      can increase reaction rates by 100 million to 10 billion times faster than any
      normal chemical reaction. Due to development in recombinant technology and
      protein engineering, enzymes have evolved as an important molecule that has been
      widely used in different industrial and therapeutical purposes. Microbial enzymes
      are currently acquiring much attention with rapid development of enzyme
      technology. Microbial enzymes are preferred due to their economic feasibility,
      high yields, consistency, ease of product modification and optimization, regular
      supply due to absence of seasonal fluctuations, rapid growth of microbes on
      inexpensive media, stability, and greater catalytic activity. Microbial enzymes
      play a major role in the diagnosis, treatment, biochemical investigation, and
      monitoring of various dreaded diseases. Amylase and lipase are two very important
      enzymes that have been vastly studied and have great importance in different
      industries and therapeutic industry. In this review, an approach has been made to
      highlight the importance of different enzymes with special emphasis on amylase
      and lipase in the different industrial and medical fields. 

PMID- 24106703
TI  - Evaluation of a new lipase from Staphylococcus sp. for detergent additive
      capability.
AB  - Lipases are the enzymes of choice for laundry detergent industries owing to their
      triglyceride removing ability from the soiled fabric which eventually reduces the
      usage of phosphate-based chemical cleansers in the detergent formulation. In the
      present study, a partially purified bacterial lipase from Staphylococcus arlettae
      JPBW-1 isolated from the rock salt mine has been assessed for its triglyceride
      removing ability by developing a presoak solution so as to use lipase as an
      additive in laundry detergent formulations. The effects of selected surfactants,
      commercial detergents, and oxidizing agents on lipase stability were studied in a
      preliminary evaluation for its further usage in the industrial environment.
      Partially purified lipase has shown good stability in presence of surfactants,
      commercial detergents, and oxidizing agents. Washing efficiency has been found to
      be enhanced while using lipase with 0.5% nonionic detergent than the anioinic
      detergent. The wash performance using 0.5% wheel with 40 U lipase at 40 degrees C
      in 45 min results in maximum oil removal (62%) from the soiled cotton fabric.
      Hence, the present study opens the new era in enzyme-based detergent sector for
      formulation of chemical-free detergent using alkaline bacterial lipase. 

PMID- 24106705
TI  - Determinants of thyrotoxic cardiomyopathy recovery.
AB  - The purpose was to evaluate the effect of the disease duration prior to
      treatment, thyroid hormones level, or both on the reversibility of dilated
      cardiomyopathy. Between January 2006 and December 2010, a longitudinal study with
      a 6 months follow-up was carried on. One hundred and seventy patients with
      hyperthyroidism were referred to the cardiologist, and 127 had a 6 months
      followup after antithyroid treatment and were evaluated by echocardiography.
      Dilated cardiomyopathy reversibility criteria were established according to
      echocardiographic parameters. Complete reversibility existed when all parameters
      were met, partial reversibility when LVEF was >=55% plus two or three other
      parameters, and no reversibility when LVEF was <=55% regardless of other
      parameters. The results showed that echocardiography parameters related to the
      regression of myocardial mass were associated with a disease duration shorter
      than 10.38 months. This was the main predictive variable for reversal of dilated
      cardiomyopathy, followed by beta -blocker treatment, and the last predictive
      variable was the serum level of free triiodothyronine. This study showed that the
      effect on the myocardium related to thyrotoxicosis was associated with the
      disease duration before treatment. 

PMID- 24106704
TI  - Immunomodulatory effects of adipose-derived stem cells: fact or fiction?
AB  - Adipose-derived stromal cells (ASCs) are often referred to as adipose-derived
      stem cells due to their potential to undergo multilineage differentiation. Their
      promising role in tissue engineering and ability to modulate the immune system
      are the focus of extensive research. A number of clinical trials using ASCs are
      currently underway to better understand the role of such cell niche in enhancing
      or suppressing the immune response. If governable, such immunoregulatory role
      would find application in several conditions in which an immune response is
      present (i.e., autoimmune conditions) or feared (i.e., solid organ or
      reconstructive transplantation). Although allogeneic ASCs have been shown to
      prevent acute GvHD in both preclinical and clinical studies, their potential
      warrants further investigation. Well-designed and standardized clinical trials
      are necessary to prove the role of ASCs in the treatment of immune disorders or
      prevention of tissue rejection. In this paper we analyze the current literature
      on the role of ASCs in immunomodulation in vitro and in vivo and discuss their
      potential in regulating the immune system in the context of transplantation. 

PMID- 24106706
TI  - The StartReact effect on self-initiated movements.
AB  - Preparation of the motor system for movement execution involves an increase in
      excitability of motor pathways. In a reaction time task paradigm, a startling
      auditory stimulus (SAS) delivered together with the imperative signal (IS)
      shortens reaction time significantly. In self-generated tasks we considered that
      an appropriately timed SAS would have similar effects. Eight subjects performed a
      ballistic wrist extension in two blocks: reaction, in which they responded to a
      visual IS, and action, in which they moved when they wished within a
      predetermined time window. In 20-25% of the trials, a SAS was applied. We
      recorded electromyographic activity of wrist extension and wrist movement
      kinematic variables. No effects of SAS were observed in action trials when
      movement was performed before or long after SAS application. However, a cluster
      of action trials was observed within 200 ms after SAS. These trials showed larger
      EMG bursts, shorter movement time, shorter time to peak velocity, and higher peak
      velocity than other action trials (P < 0.001 for all), with no difference from
      Reaction trials containing SAS. The results show that SAS influences the
      execution of self-generated human actions as it does with preprogrammed reaction
      time tasks during the assumed building up of preparatory activity before
      execution of the willed motor action. 

PMID- 24106707
TI  - Improvement of daptomycin production in Streptomyces roseosporus through the
      acquisition of pleuromutilin resistance.
AB  - Daptomycin, a cyclic lipopeptide antibiotic produced by Streptomyces roseosporus,
      displays potent activity against a variety of gram-positive pathogens. There is a
      demand for generating high-producing strains for industrial production of this
      valuable antibiotic. Ribosome engineering is a powerful strategy to enhance the
      yield of secondary metabolites. In this study, the effect of a diterpenoid
      antibiotic pleuromutilin resistance mutation on daptomycin production was
      assessed. Spontaneous pleuromutilin-resistant derivatives of S. roseosporus were
      isolated. Sequencing of rplC locus (encoding the ribosomal protein L3) showed a
      point mutation at nt 455, resulting in the substitution of glycine with valine.
      G152V mutants showed increased production of daptomycin by approximately 30% in
      comparison with the wild-type strain. Its effect on daptomycin production was due
      to enhanced gene transcription of the daptomycin biosynthetic genes. In
      conclusion, pleuromutilin could be used as a novel ribosome engineering agent to
      improve the production of desired secondary metabolites. 

PMID- 24106708
TI  - Dose- and time-dependent apoptosis induced by avian H9N2 influenza virus in human
      cells.
AB  - To understand human response to avian H9N2 influenza, we investigated the effects
      of the viral infection on A549, HepG2, and HeLa cells at low and high MOIs. To
      identify virus-host interplay, expression of Mx and NP genes was measured in the
      cells supernatants. Cell viability and apoptosis were evaluated by MTT assay, DNA
      fragmentation, and florescent staining. The virus titration and NP gene
      transcript levels indicate lower susceptibility of HeLa cell to H9N2 replication
      than other cells. Although H9N2 did produce a faster CPE in HepG2, high dose of
      the virus induced apoptosis within early stage of A549 infection. The DNA
      laddering was enhanced in the cell correlated with increase in virus transcripts.
      The undetectable to different regulation levels of Mx gene were observed in
      response to H9N2 infection suggesting that an insufficient antiviral defense in
      the noncompetent-IFN HepG2 cell promotes efficient viral replication. These
      results showed that the permissivity of HepG2 for H9N2 is comparable with A549;
      however, liver cells are not target tissue respond to the infection. These data
      revealed that the H9N2 virus induced apoptosis signaling via mitochondrial
      pathway in human alveolar epithelial cells, indicating that the induction may be
      associated with a dose-dependent manner. 

PMID- 24106709
TI  - Allergy or tolerance: reduced inflammatory cytokine response and concomitant IL
      10 production of lymphocytes and monocytes in symptom-free titanium dental
      implant patients.
AB  - Hypersensitivity reactions to titanium (Ti) are very rare. Thus, we assessed the
      proinflammatory response and also potential tolerance favoring in vitro
      reactivity of human blood lymphocytes and monocytes (PBMC) to Ti in healthy
      individuals (14 without, 6 with complication-free dental Ti implants). The
      proliferation index (SI) in lymphocyte transformation test (LTT) and production
      of cytokines linked to innate immune response (IL-1 beta , IL-6, and TNF alpha )
      or immune regulation (IL-10) were assessed in response to TiO2 particles or Ti
      discs. In both groups, the Ti-LTT reactivity was not enhanced (e.g., SI < 3). The
      control antigen tetanus toxoid (TT) gave adequate reactivity (median SI
      individuals without/with implant: 20.6 +/- 5.97/19.58 +/- 2.99). Individuals
      without implant showed higher cytokine response to Ti materials than individuals
      with symptom-free implants; for example, TiO2 rutile particle induced increase of
      IL-1 beta 70.27-fold/8.49-fold versus control medium culture. PBMC of 5 of the 6
      individuals with complication-free Ti implants showed an ex vivo ongoing
      production of IL-10 (mean 4.18 +/- 2.98 pg/mL)-but none of the 14 controls showed
      such IL-10 production. Thus in vitro IL-1 beta -, IL-6-, and TNF- alpha
      production reflects "normal" unspecific immune response to Ti. This might be
      reduced by production of tolerogenic IL-10 in individuals with symptom-free Ti
      dental implants. 

PMID- 24106710
TI  - Does off-pump coronary artery bypass grafting negatively impact long-term
      survival and freedom from reintervention?
AB  - Recently published evidence has raised concerns about worse late mortality and
      increasing need for reintervention after off-pump coronary artery bypass
      grafting. We undertook this study to assess the impact of off-pump coronary
      artery bypass grafting on survival and freedom from reintervention at 10 years.
      From January 2002 to December 2002, 307 consecutive patients who had isolated
      multivessel off-pump coronary artery bypass grafting at our institution were
      compared to a control group of 397 patients that underwent multivessel on-pump
      coronary artery bypass grafting during the same period. In addition, univariate
      and risk-adjusted comparisons between the two groups were performed at 10 years.
      Kaplan-Meier survival was similar for the two cohorts. After adjusting for
      clinical covariates, off-pump coronary artery bypass grafting did not emerge as a
      significant independent predictor of long-term mortality (Hazard Ratio 0.91; 95%
      Confidence Interval 0.70-1.12), readmission to hospital for cardiac cause (Hazard
      Ratio 0.96; 95% Confidence Interval 0.78-1.10), or the need for reintervention
      (Hazard Ratio 0.93; 95% Confidence Interval 0.87-1.05). Off-pump coronary artery
      bypass grafting compared with on-pump coronary artery bypass grafting does not
      adversely impact survival or freedom from reintervention at a 10-year follow-up. 

PMID- 24106711
TI  - Association of seat height and arm position on the five times sit-to-stand test
      times of stroke survivors.
AB  - OBJECTIVES: To investigate (1) the association of seat height and (2) the
      association of arm position on the five times sit-to-stand test (FTSTS) times of
      individuals with stroke. DESIGN: A cross-sectional study. SETTING: University
      based rehabilitation centre. SUBJECTS: Patients (n = 43) with chronic stroke.
      METHODS: The times in completing the FTSTS with different seat height (85%, 100%,
      and 115% knee height) and arm positions (arms across chest, hands on thighs).
      RESULTS: FTSTS times were significantly different between 85% and 100% seat
      heights, and between the 85% and 115% seat heights in both arm positions.
      However, there was no significant difference between the FTSTS times with the two
      arm positions at any seat height tested. CONCLUSION: Seat heights lower than the
      knee height result in longer FTSTS times, whereas arms positions did not
      significantly affect the FTSTS times.

PMID- 24106712
TI  - "Zebrafishing" for novel genes relevant to the glomerular filtration barrier.
AB  - Data for genes relevant to glomerular filtration barrier function or proteinuria
      is continually increasing in an era of microarrays, genome-wide association
      studies, and quantitative trait locus analysis. Researchers are limited by
      published literature searches to select the most relevant genes to investigate.
      High-throughput cell cultures and other in vitro systems ultimately need to
      demonstrate proof in an in vivo model. Generating mammalian models for the genes
      of interest is costly and time intensive, and yields only a small number of test
      subjects. These models also have many pitfalls such as possible embryonic
      mortality and failure to generate phenotypes or generate nonkidney specific
      phenotypes. Here we describe an in vivo zebrafish model as a simple vertebrate
      screening system to identify genes relevant to glomerular filtration barrier
      function. Using our technology, we are able to screen entirely novel genes in 4-6
      weeks in hundreds of live test subjects at a fraction of the cost of a mammalian
      model. Our system produces consistent and reliable evidence for gene relevance in
      glomerular kidney disease; the results then provide merit for further analysis in
      mammalian models. 

PMID- 24106714
TI  - Characterization of C-S Lyase from C. diphtheriae: a possible target for new
      antimicrobial drugs.
AB  - The emergence of antibiotic resistance in microbial pathogens requires the
      identification of new antibacterial drugs. The biosynthesis of methionine is an
      attractive target because of its central importance in cellular metabolism.
      Moreover, most of the steps in methionine biosynthesis pathway are absent in
      mammals, lowering the probability of unwanted side effects. Herein, detailed
      biochemical characterization of one enzyme required for methionine biosynthesis,
      a pyridoxal-5'-phosphate (PLP-) dependent C-S lyase from Corynebacterium
      diphtheriae, a pathogenic bacterium that causes diphtheria, has been performed.
      We overexpressed the protein in E. coli and analyzed substrate specificity, pH
      dependence of steady state kinetic parameters, and ligand-induced spectral
      transitions of the protein. Structural comparison of the enzyme with cystalysin
      from Treponema denticola indicates a similarity in overall folding. We used site
      directed mutagenesis to highlight the importance of active site residues Tyr55,
      Tyr114, and Arg351, analyzing the effects of amino acid replacement on catalytic
      properties of enzyme. Better understanding of the active site of C. diphtheriae C
      S lyase and the determinants of substrate and reaction specificity from this work
      will facilitate the design of novel inhibitors as antibacterial therapeutics. 

PMID- 24106713
TI  - Recombinant rat CC10 protein inhibits PDGF-induced airway smooth muscle cells
      proliferation and migration.
AB  - Abnormal migration and proliferation of airway smooth muscle cells (ASMCs) in the
      airway cause airway wall thickening, which is strongly related with the
      development of airway remodeling in asthma. Clara cell 10 kDa protein (CC10),
      which is secreted by the epithelial clara cells of the pulmonary airways, plays
      an important role in the regulation of immunological and inflammatory processes.
      Previous studies suggested that CC10 protein had great protective effects against
      inflammation in asthma. However, the effects of CC10 protein on ASMCs migration
      and proliferation in airway remodeling were poorly understood. In this study, we
      constructed the pET-22b-CC10 recombinant plasmid, induced expression and purified
      the recombinant rat CC10 protein from E. coli by Ni(2+) affinity chromatography
      and ion exchange chromatography purification. We investigated the effect of
      recombinant rat CC10 protein on platelet-derived growth factor (PDGF)-BB-induced
      ASMCs proliferation and migration. Our results demonstrated that the recombinant
      CC10 protein could inhibit PDGF-BB-induced cell viability, proliferation and
      migration. Western blot analysis showed that PDGF-BB-induced activation of cyclin
      D1 was inhibited by CC10. These findings implicated that CC10 could inhibit
      increased ASMCs proliferation, and migration induced by PDGF-BB, and this
      suppression effect might be associated with inhibition of cyclin D1 expression,
      which might offer hope for the future treatment of airway remodeling. 

PMID- 24106715
TI  - Formulation development and evaluation of hybrid nanocarrier for cancer therapy:
      Taguchi orthogonal array based design.
AB  - Taguchi orthogonal array design is a statistical approach that helps to overcome
      limitations associated with time consuming full factorial experimental design. In
      this study, the Taguchi orthogonal array design was applied to establish the
      optimum conditions for bovine serum albumin (BSA) nanocarrier (ANC) preparation.
      Taguchi method with L9 type of robust orthogonal array design was adopted to
      optimize the experimental conditions. Three key dependent factors namely, BSA
      concentration (% w/v), volume of BSA solution to total ethanol ratio (v : v), and
      concentration of diluted ethanolic aqueous solution (% v/v), were studied at
      three levels 3%, 4%, and 5% w/v; 1 : 0.75, 1 : 0.90, and 1 : 1.05 v/v; 40%, 70%,
      and 100% v/v, respectively. The ethanolic aqueous solution was used to impart
      less harsh condition for desolvation and attain controlled nanoparticle
      formation. The interaction plot studies inferred the ethanolic aqueous solution
      concentration to be the most influential parameter that affects the particle size
      of nanoformulation. This method (BSA, 4% w/v; volume of BSA solution to total
      ethanol ratio, 1 : 0.90 v/v; concentration of diluted ethanolic solution, 70%
      v/v) was able to successfully develop Gemcitabine (G) loaded modified albumin
      nanocarrier (M-ANC-G) of size 25.07 +/- 2.81 nm (zeta = -23.03 +/- 1.015 mV) as
      against to 78.01 +/- 4.99 nm (zeta = -24.88 +/- 1.37 mV) using conventional
      method albumin nanocarrier (C-ANC-G). Hybrid nanocarriers were generated by
      chitosan layering (solvent gelation technique) of respective ANC to form C-HNC-G
      and M-HNC-G of sizes 125.29 +/- 5.62 nm (zeta = 12.01 +/- 0.51 mV) and 46.28 +/-
      2.21 nm (zeta = 15.05 +/- 0.39 mV), respectively. Zeta potential, entrapment, in
      vitro release, and pH-based stability studies were investigated and influence of
      formulation parameters are discussed. Cell-line-based cytotoxicity assay (A549
      and H460 cells) and cell internalization assay (H460 cell line) were performed to
      assess the influence on the bioperformance of these nanoformulations. 

PMID- 24106716
TI  - Familiar music as an enhancer of self-consciousness in patients with Alzheimer's
      disease.
AB  - The main objective of this paper is to examine the impact of familiar music on
      self-consciousness (SC) in patients with Alzheimer's disease (AD). For this
      purpose, two AD groups of 20 patients matched by age, educational level, gender,
      illness duration, and cognitive state were assessed using an SC questionnaire
      before and after music intervention. The SC questionnaire measured several
      aspects: personal identity, anosognosia, affective state, body representation,
      prospective memory, introspection and moral judgments. One AD group received
      familiar music stimulation and another AD group unfamiliar music stimulation over
      three months. The AD patients who received a familiar music intervention showed a
      stabilization or improvement in aspects of SC. By contrast, control AD group
      showed a deterioration of most of the SC aspects after unfamiliar music
      stimulation, except the SC aspects of body representation and affective state.
      Familiar music stimulation could be considered as an enhancer of SC in patients
      with Alzheimer's disease. 

PMID- 24106717
TI  - Proliferative activity in Libyan breast cancer with comparison to European and
      Central African patients.
AB  - BACKGROUND: We evaluated the relation of proliferative indices with
      clinicopathological features and prognosis in breast cancer (BC) of Libyan female
      patients. The data were compared with corresponding results in Finland and
      Nigeria. PATIENTS AND METHODS: Histological samples of breast cancer from 130
      patients were retrospectively studied. Mitotic activity index (MAI) and
      standardized mitotic index (SMI) were estimated. RESULTS: There were
      statistically significant correlations between the proliferative indices and most
      clinicopathological features, with the strongest association observed for
      histological grade (P = 0.01 for SMI and P = 0.003 for MAI). The proliferative
      differences between Libyan, Nigerian, and Finnish population were prominent. The
      mean values of SMI and MAI in Libyan BC patients were 32.1 mitotic figures per
      square millimeter and 27.3 mitotic figures per 10 high-power fields,
      respectively. This is clearly lower than those in Nigeria but much higher than
      those in Finland. The differences between countries are seen in whole material
      and are also present in subgroups. The results indicated that mitotic activities
      can be reliable prognostic indicators in Libyan BCs, as they were among Finnish
      and Nigerian females. Univariate and multivariate analyses found at cut-offs of
      19 and 44 mitosis/mm(2) of SMI were the most significant prognostic factors.
      CONCLUSIONS: Proliferative indices with careful estimation of the MAI and SMI
      could be applied as quantitative criteria for Libyan BC to separate the patients
      into good, moderate, and bad prognosis groups.

PMID- 24106718
TI  - Osteogenic matrix cell sheet transplantation enhances early tendon graft to bone
      tunnel healing in rabbits.
AB  - The objective of this study was to determine whether osteogenic matrix cell
      sheets (OMCS) could induce bone formation around grafted tendons, thereby
      enhancing early stage tendon to bone tunnel healing in skeletally mature male
      Japanese white rabbits. First, the osteogenic potential of rabbit OMCS was
      evaluated. Then, the OMCS were transplanted into the interface between the
      grafted tendon and the bone tunnel created at the tibia. Histological assessments
      and biomechanical tensile testing were performed after 3 weeks. The rabbit OMCS
      showed high alkaline phosphatase (ALP) activity, positive staining of ALP, and
      osteogenic potential when transplanted subcutaneously with beta tricalcium
      phosphate disks. Newly formed bony walls and positive collagen type I staining
      were seen around the grafted tendon with OMCS transplantation, whereas such bony
      walls were thinner or less frequent without OMCS transplantation. Micro-computed
      tomography images showed significantly higher bone volume in the OMCS
      transplantation group. The pullout strength was significantly higher with OMCS
      (0.74 +/- 0.23 N/mm(2)) than without OMCS (0.58 +/- 0.15 N/mm(2)). These results
      show that OMCS enhance early tendon to bone tunnel healing. This method can be
      applied to cases requiring early tendon to bone tunnel healing after ligament
      reconstruction surgery. 

PMID- 24106719
TI  - Listeria monocytogenes meningitis in adults: the Czech Republic experience.
AB  - BACKGROUND: Listeria monocytogenes (LM) is currently the third most frequent
      pathogen of bacterial meningitis in adults. METHODS: A prospective study of
      patients with LM meningitis in a Czech tertiary care hospital, carried out from
      1997 to 2012. RESULTS: Thirty-one patients were diagnosed with LM meningitis,
      which was 7% of a total of 440 adult patients with acute bacterial meningitis
      (ABM) over a 16-year period. Their median age was 63 years, range 26-80 years.
      Nineteen patients (61%) had underlying immunocompromising comorbidity; 15
      patients (48%) were older than 65 years. Fourteen patients (45%) had arterial
      hypertension. The typical triad of fever, neck stiffness, and altered mental
      status was present in 21 patients (68%). The median count of cerebrospinal fluid
      (CSF) leukocytes was 680/MUL, protein level 2.6 g/L, and glucose ratio 0.28. Four
      patients (13%) died, and nine (29%) survived with moderate to severe sequelae.
      CONCLUSION: LM meningitis is known to affect immunosuppressed and elderly
      patients. Arterial hypertension seems to be another important predisposing
      factor. Clinical symptoms, CSF findings, and disease outcomes, did not
      significantly differ from other community-acquired ABM in our study, although the
      CSF leukocyte count was lower. Ampicillin showed good clinical and
      bacteriological efficacy in the majority of patients.

PMID- 24106720
TI  - TLR stimulation of bone marrow lymphoid precursors from childhood acute leukemia
      modifies their differentiation potentials.
AB  - Acute leukemias are the most frequent childhood malignancies worldwide and remain
      a leading cause of morbidity and mortality of relapsed patients. While remarkable
      progress has been made in characterizing genetic aberrations that may control
      these hematological disorders, it has also become clear that abnormalities in the
      bone marrow microenvironment might hit precursor cells and contribute to disease.
      However, responses of leukemic precursor cells to inflammatory conditions or
      microbial components upon infection are yet unexplored. Our previous work and
      increasing evidence indicate that Toll-like receptors (TLRs) in the earliest
      stages of lymphoid development in mice and humans provide an important mechanism
      for producing cells of the innate immune system. Using highly controlled co
      culture systems, we now show that lymphoid precursors from leukemic bone marrow
      express TLRs and respond to their ligation by changing cell differentiation
      patterns. While no apparent contribution of TLR signals to tumor progression was
      recorded for any of the investigated diseases, the replenishment of innate cells
      was consistently promoted upon in vitro TLR exposure, suggesting that early
      recognition of pathogen-associated molecules might be implicated in the
      regulation of hematopoietic cell fate decisions in childhood acute leukemia. 

PMID- 24106721
TI  - Periodontal disease is an independent predictor of intracardiac calcification.
AB  - BACKGROUND: Periodontitis is the most common chronic inflammatory condition
      worldwide and is associated with incident coronary disease. HYPOTHESIS: We
      hypothesized that periodontal disease would also be associated with cardiac
      calcification, a condition which shares many risk factors with atherosclerosis
      and is considered a marker of subclinical atherosclerosis. METHODS: Cross
      sectional study at two sites (USA and Japan) involving subjects with both
      clinical echocardiograms and detailed dental examinations. Semiquantitative
      scoring systems were used to assess severity of periodontal disease and
      echocardiographic calcification. RESULTS: Fifty-six of 73 subjects (77%) had
      cardiac calcifications, and 51% had moderate to severe periodontal disease (score
      > 2). In unadjusted analysis, a significant relationship between periodontal
      score and cardiac calcification (Spearman rho = 0.4, P = 0.001) was noted, with
      increases in mean calcification score seen across increasing levels of
      periodontal disease. On multivariate logistic regression, adjusted for age,
      gender, race, glomerular filtration rate, and traditional risk factors, this
      association remained significant (P = 0.024). There was no significant
      interaction by study site, race, or gender. CONCLUSIONS: In a multiracial
      population, we found a significant association between the degree of periodontal
      disease, a chronic inflammatory condition, and cardiac calcification. Further,
      higher periodontal scores were associated with greater degrees of calcification.

PMID- 24106722
TI  - Preliminary characterization of genipin-cross-linked silk sericin/poly(vinyl
      alcohol) films as two-dimensional wound dressings for the healing of superficial
      wounds.
AB  - The genipin-cross-linked silk sericin/poly(vinyl alcohol) (PVA) films were
      developed aiming to be applied as two-dimensional wound dressings for the
      treatment of superficial wounds. The effects of genipin cross-linking
      concentration on the physical and biological properties of the films were
      investigated. The genipin-cross-linked silk sericin/PVA films showed the
      increased surface density, tensile strength, and percentage of elongation, but
      decreased percentage of light transmission, water vapor transmission rate, and
      water swelling, compared to the non-cross-linked films. This explained that the
      cross-linking bonds between genipin and silk sericin would reduce the mobility of
      molecular chains within the films, resulting in the more rigid molecular
      structure. Silk sericin was released from the genipin-cross-linked films in a
      sustained manner. In addition, either L929 mouse fibroblast or HaCat keratinocyte
      cells showed high percentage of viability when cultured on the silk sericin/PVA
      films cross-linked with 0.075 and 0.1% w/v genipin. The in vivo safety test
      performed according to ISO 10993-6 confirmed that the genipin-cross-linked silk
      sericin/PVA films were safe for the medical usages. The efficacy of the films for
      the treatment of superficial skin wounds will be further investigated in vivo and
      clinically. The genipin-cross-linked silk sericin/PVA films would be promising
      choices of two-dimensional wound dressings for the treatment of superficial
      wounds. 

PMID- 24106723
TI  - An immunocytochemical study of interchromatin granule clusters in early mouse
      embryos.
AB  - Interchromatin granule clusters (IGCs) are universal nuclear domains. Their
      molecular composition and functions were studied in detail in somatic cells.
      Here, we studied IGCs in the nuclei of early mouse embryos during zygotic gene
      activation (ZGA). We found that the size of IGCs gradually increases during
      realization of ZGA events. Using immunocytochemical approaches, we showed that
      the molecular composition of IGCs is also modified in mouse embryos. The
      hyperphosphorylated form of RNA polymerase II and the transcription factor TFIID
      have been revealed in IGCs before the end of ZGA. Association of these factors
      with IGCs became more noticeable during ZGA realization. Our data suggest that
      IGCs in early mouse embryos have some functional peculiarities connected most
      probably with IGC formation de novo. We believe that IGCs in early mouse embryos
      not only are storage sites of splicing factors but also may be involved in mRNA
      metabolism and represent the multifunctional nuclear domains. 

PMID- 24106725
TI  - Esophagitis dissecans superficialis: a case report and literature review.

PMID- 24106724
TI  - Myogenic differentiation of mesenchymal stem cells in a newly developed
      neurotised AV-loop model.
AB  - Generation of axially vascularized muscle tissue constitutes a promising new
      approach to restoration of damaged muscle tissue. Mesenchymal stemcells (MSC),
      with their ability to be expanded to large cell numbers without losing their
      differentiation capacity into the myogenic lineage, could offer a promising cell
      source to generate neomuscle tissue. In vitro experiments showed that cocultures
      of primary myoblasts and MSC undergo myogenic differentiation by stimulation with
      bFGF and dexamethasone. A newly developed AV-Loop model with neurotization was
      established in this study. It encompasses axial vascularization and the
      additional implantation of a motor nerve serving as myogenic stimulator.
      Myoblasts and MSCs were coimplantated in a prevascularized isolation chamber.
      Cells were differentiated by addition of bFGF and dexamethasone plus implantation
      of a motor nerve. After 8 weeks, we could observe areas of myogenic
      differentiation with alpha -sarcomeric actin and MHC expression in the
      constructs. Quantitative PCR analysis showed an expression of myogenic markers in
      all specimens. Thus, neurotization and addition of bFGF and dexamethasone allow
      myogenic differentiation of MSC in an axially vascularized in vivo model for the
      first time. These findings are a new step towards clinical applicability of
      skeletal muscle tissue engineering and display its potential for regenerative
      medicine. 

PMID- 24106726
TI  - Subsequent entry biologics - opportunities and challenges.

PMID- 24106727
TI  - Overview of subsequent entry biologics for the management of inflammatory bowel
      disease and Canadian Association of Gastroenterology position statement on
      subsequent entry biologics.

PMID- 24106728
TI  - Minimal hepatic encephalopathy.
AB  - Minimal hepatic encephalopathy (MHE) is the earliest form of hepatic
      encephalopathy and can affect up to 80% of cirrhotic patients. By definition, it
      has no obvious clinical manifestation and is characterized by neurocognitive
      impairment in attention, vigilance and integrative function. Although often not
      considered to be clinically relevant and, therefore, not diagnosed or treated,
      MHE has been shown to affect daily functioning, quality of life, driving and
      overall mortality. The diagnosis of MHE has traditionally been achieved through
      neuropsychological examination, psychometric tests or the newer critical flicker
      frequency test. A new smartphone application (EncephalApp Stroop Test) may serve
      to function as a screening tool for patients requiring further testing. In
      addition to physician reporting and driving restrictions, medical treatment for
      MHE includes non-absorbable disaccharides (eg, lactulose), probiotics or
      rifaximin. Liver transplantation may not result in reversal of the cognitive
      deficits associated with MHE. 

PMID- 24106729
TI  - Antidepressant prophylaxis reduces depression risk but does not improve sustained
      virological response in hepatitis C interferon recipients without depression at
      baseline: a systematic review and meta-analysis.
AB  - BACKGROUND: Depression complicates interferon-based hepatitis C virus (HCV)
      antiviral therapy in 10% to 40% of cases, and diminishes patient well-being and
      ability to complete a full course of therapy. As a consequence, the likelihood of
      achieving a sustained virological response (SVR [ie, permanent viral
      eradication]) is reduced. OBJECTIVE: To systematically review the evidence of
      whether pre-emptive antidepressant prophylaxis started before HCV antiviral
      initiation is beneficial. METHODS: Inclusion was restricted to randomized
      controlled trials in which prophylactic antidepressant therapy was started at
      least two weeks before the initiation of HCV antiviral treatment. Studies
      pertaining to patients with active or recent depressive symptoms before
      commencing HCV antiviral therapy were excluded. English language articles from
      1946 to July 2012 were included. The MEDLINE, Embase and Cochrane Central
      databases were searched. Where possible, meta-analyses were conducted evaluating
      the effect of antidepressant prophylaxis on SVR and major depression as well as
      on Montgomery-Asberg Depression Rating Scale and Beck Depression Index scores at
      four, 12 and 24 weeks. The Cochrane Collaboration tool was used to assess bias
      risk. RESULTS: Six randomized clinical trials involving 522 patients met the
      inclusion criteria. Although the frequency of on-treatment clinical depression
      was decreased with antidepressant prophylaxis (risk ratio 0.60 [95% CI 0.38 to
      0.93]; P=0.02; I2=24%), no benefit to SVR was identified (risk ratio 1.08 [95% CI
      0.74 to 1.57]; P=0.69; I2=58%). CONCLUSION: This practice is not justified to
      improve SVR in populations free of active depressive symptoms leading up to HCV
      antiviral therapy.

PMID- 24106730
TI  - Capnography improves detection of apnea during procedural sedation for
      percutaneous transhepatic cholangiodrainage.
AB  - BACKGROUND: Capnography provides noninvasive monitoring of ventilation and can
      enable early recognition of altered respiration patterns and apnea. OBJECTIVE: To
      compare the detection of apnea and the prediction of oxygen desaturation and
      hypoxemia using capnography versus clinical surveillance during procedural
      sedation for percutaneous transhepatic cholangiodrainage (PTCD). METHODS: Twenty
      consecutive patients scheduled for PTCD were included in the study. All patients
      were sedated during the procedure using midazolam and propofol. Aside from
      standard monitoring, additional capnographic monitoring was used and analyzed by
      an independent observer. RESULTS: The mean (+/- SD) cumulative duration of apnea
      demonstrated by capnography was significantly longer than the mean cumulative
      duration of clinically detected apnea (207.5 +/- 348.8 s versus 8.2 +/- 17.9 s;
      P=0.015). The overall number of detected episodes of apnea was also significantly
      different (113 versus seven; P=0.012). There were 15 events of oxygen
      desaturation (decrease in oxygen saturation [SaO2] >= 5%), which were predicted
      in eight of 15 cases by capnography and in one of 15 cases by clinical
      observation. There were three events of hypoxemia (SaO2 <90%) that were predicted
      in three of three cases by capnography and in one of three cases by clinical
      observation. CONCLUSION: Capnographic monitoring was superior to clinical
      surveillance in the detection of apnea and in the prediction of oxygen
      desaturation during procedural sedation for PTCD.

PMID- 24106731
TI  - A pilot study examining the relationship among Crohn disease activity, glucagon
      like peptide-2 signalling and intestinal function in pediatric patients.
AB  - BACKGROUND/ OBJECTIVES: The relationship between the enteroendocrine hormone
      glucagon-like peptide 2 (GLP-2) and intestinal inflammation is unclear. GLP-2
      promotes mucosal growth, decreases permeability and reduces inflammation in the
      intestine; physiological stimulation of GLP-2 release is triggered by nutrient
      contact. The authors hypothesized that ileal Crohn disease (CD) affects GLP-2
      release. METHODS: With ethics board approval, pediatric patients hospitalized
      with CD were studied; controls were recruited from local schools. Inclusion
      criteria were endoscopy-confirmed CD (primarily of the small intestine) with a
      disease activity index >150. Fasting and postprandial GLP-2 levels and
      quantitative urinary recovery of orally administered 3-O-methyl-glucose (active
      transport) and lactulose/mannitol (passive) were quantified during the acute and
      remission phases. RESULTS: Seven patients (mean [+/- SD] age 15.3 +/- 1.3 years)
      and 10 controls (10.3 +/- 1.6 years) were studied. In patients with active
      disease, fasting levels of GLP-2 remained stable but postprandial levels were
      reduced. Patients with active disease exhibited reduced glucose absorption and
      increased lactulose/mannitol recovery; all normalized with disease remission. The
      change in the lactulose/mannitol ratio was due to both reduced lactulose and
      increased mannitol absorption. CONCLUSIONS: These findings suggest that pediatric
      patients with acute ileal CD have decreased postprandial GLP-2 release, reduced
      glucose absorption and increased intestinal permeability. Healing of CD resulted
      in normalization of postprandial GLP-2 release and mucosal functioning (nutrient
      absorption and permeability), the latter due to an increase in mucosal surface
      area. These findings have implications for the use of GLP-2 and feeding
      strategies as a therapy in CD patients; further studies of the effects of
      inflammation and the GLP-2 axis are recommended.

PMID- 24106733
TI  - A hybrid FLIM-elastic net platform for label free profiling of breast cancer.
AB  - We report a label-free fluorescence lifetime profiling strategy to classify
      breast cancer cells, MCF10CA1h (malignant), MCF10A (nonmalignant), and MCF10AneoT
      (premalignant) in different stages of malignancy. Fluorescence Lifetime Imaging
      Microscopy (FLIM) was used to record the lifetime of autofluorescence of
      endogenous flavin in MCF10 cells in different stages of malignancy. Predominant
      differences in lifetimes ascertained by multi-exponential fitting curves can be
      attributed to the different forms of flavin protein; flavin mononucleotide (FMN),
      free flavin adenine dinucleotide (FAD), semiquinone, and bound FAD. A lifetime
      map of the metabolite was derived from the contribution of the lifetime of each
      metabolite by iterative reconvolution fitting of the Time Correlated Single
      Photon Counting (TCSPC) decay curves. Lifetime maps were constructed by mapping
      the average lifetime values pixel by pixel using MATLAB. The FLIM image (150 *
      150 pixels) of each cell was extracted, resized and centered into 100 * 100
      pixels using the nearest neighbor algorithm. Principal Component Analysis (PCA)
      in conjunction with Elastic net Analysis (EnA) was then used to classify the
      different stages of MCF10 cell lines based on average lifetime values. The EnA
      model provided an excellent classification of the cells at different stages of
      tumorigenesis yielding 100% accuracy. 

PMID- 24106732
TI  - Gastric biopsies: the gap between evidence-based medicine and daily practice in
      the management of gastric Helicobacter pylori infection.
AB  - BACKGROUND: Many consider histology to be the gold standard for Helicobacter
      pylori detection. Because the number and distribution of H pylori organisms vary,
      particularly in patients taking proton pump inhibitors (PPIs), the American
      Gastroenterological Association recommends discontinuing PPIs two weeks before
      endoscopy, and taking biopsies from both the body and antrum. OBJECTIVE: To
      assess the influence of clinical practice on the histopathological detection of H
      pylori infection. METHODS: Electronic patient records were evaluated for the
      sites of gastric sampling and PPI use at endoscopy. One hundred fifty cases with
      biopsies taken from both antrum and body were randomly selected for pathological
      re-review with special stains. The gastric regions sampled, H pylori distribution
      and influence of clinical factors on pathological interpretation were assessed.
      RESULTS: Between 2005 and 2010, 10,268 biopsies were taken to detect H pylori.
      Only one region was sampled in 60% of patients (antrum 47%, body 13%). Re-review
      of biopsies taken from both antrum and body indicated that the correct regions
      were sampled in only 85 (57%) patients. Of these, 54 were H pylori positive and
      96 were H pylori negative. H pylori was present in the antrum in only 15% of the
      patients and body only in 21%. Of 96 H pylori-negative patients, two were
      reinterpreted as positive. Forty-seven per cent of patients were taking PPIs at
      endoscopy, contributing to both false-negative and false-positive diagnoses.
      CONCLUSION: Despite national and international guidelines for managing H pylori
      infection, the American Gastroenterological Association guidelines are
      infrequently adhered to, with PPIs frequently contributing to false diagnosis;
      sampling one region only increases the likelihood of missing active infection by
      at least 15%.

PMID- 24106734
TI  - A novel protease activity assay method based on an engineered autoinhibited
      protein using an enzyme-linked immunoassay.
AB  - Proteases are involved in various biological phenomena, and their aberrant
      activity can be an important indicator of disease. Thus, various methods have
      been developed to analyze the activities of proteases, but their wide application
      has been hampered because each method has drawbacks. In this report, we propose a
      new protease assay method based on an engineered autoinhibited protein and enzyme
      linked immunoassay (ELISA) in which a protease of interest activates the
      autoinhibited protein and the signal is amplified via ELISA. Using this concept a
      sensitive assay method for MMP2 and caspase-3 was developed. The limit of
      detection for the two proteases was as low as 7 pM for MMP2 and 0.1 pM for
      caspase-3. The autoinhibited protein is designed modularly, and the new platform
      is general enough for the development of assay methods for other proteases with
      minimal modification. 

PMID- 24106735
TI  - Aqueous synthesis of human serum albumin-stabilized fluorescent Au/Ag core/shell
      nanocrystals for highly sensitive and selective sensing of copper(II).
AB  - Utilizing human serum albumin as a reducing plus stabilizing agent, fluorescent
      Au/Ag core/shell nanocrystals (NCs) were prepared in water at pH 9.0 and at
      physiological temperature (37  degrees C). The preparation of Au/Ag NCs did not
      involve any external reducing or stabilizing agents, and thus was eco-friendly.
      Moreover, the as-prepared Au/Ag NCs exhibited excellent photoluminescence (PL)
      properties that were utilized in the development of a PL sensor for the detection
      of Cu(2+). Experimental results showed that the PL of Au/Ag NCs was almost
      linearly quenched by each increment of Cu(2+) concentration in the range of 0-200
      nM, and the corresponding linear equation had a good correlation coefficient of
      0.9959. The limit of detection for this sensor method was calculated to be 5 nM.
      In the presence of Cu(2+), the PL quenching of Au/Ag NCs was highly selective and
      sensitive in comparison to other metal ions and anions determined under the same
      conditions. In addition, the detection mechanism of this PL sensor was
      investigated. To further evaluate the analytical performance of this sensor, the
      concentrations of Cu(2+) were determined in real samples, including tap water,
      river water, gastric juice, urine and mixed solutions. 

PMID- 24106736
TI  - A novel pyrazoline-based selective fluorescent probe for detecting reduced
      glutathione and its application in living cells and serum.
AB  - A new fluorescent probe, N-(4-(1,5-diphenyl-4,5-dihydro-1H-pyrazol-3-yl)phenyl)
      2,4-dinitrobenzenesulfonamide (probe 3), was designed and synthesized as a highly
      sensitive and selective fluorescent probe for recognizing and detecting
      glutathione among biological thiols in aqueous media. Probe 3 is a nonfluorescent
      compound. On being mixed with biothiols under neutral aqueous conditions, the 2,4
      dinitrobenzenesulfoyl moiety can be cleaved off by glutathione, and the blue
      emission of the pyrazoline at 464 nm is switched on, with a fluorescence
      enhancement of 488-fold for glutathione. Furthermore, probe 3 was highly
      selective for glutathione without interference from some biologically relevant
      analytes. The detection limit of glutathione was 4.11 * 10(-7) M. The emission of
      the probe is pH independent in the physiological pH range. Moreover, the probe
      can be used for fluorescent imaging of cellular glutathione and can be used for
      detecting glutathione in calf serum. 

PMID- 24106737
TI  - Dual colorimetric and luminescent assay for dipicolinate, a biomarker of
      bacterial spores.
AB  - A binary mixture of Tb(3+) and pyrocatechol violet (PV) forms a 1 : 1 Tb(3+)/PV
      complex that can be used in a dye displacement assay. Addition of dipicolinate
      (DPA) to the Tb(3+)/DPA complex simultaneously produces a PV color change from
      blue to yellow and luminescence emission from the newly formed Tb(3+)/DPA
      complex. 

PMID- 24106738
TI  - Whole organ cross-section chemical imaging using label-free mega-mosaic FTIR
      microscopy.
AB  - FTIR chemical imaging has been demonstrated as a promising technique to construct
      automated systems to complement histopathological evaluation of biomedical tissue
      samples. The rapid chemical imaging of large areas of tissue has previously been
      a limiting factor in this application. Consequently, smaller areas of tissue have
      previously had to be sampled, possibly introducing sampling bias and potentially
      missing diagnostically important areas. In this report a high spatial resolution
      chemical image of a whole prostate cross section is shown comprising 66 million
      pixels. Each pixel represents an area 5.5 * 5.5 MUm(2) of tissue and contains a
      full infrared spectrum providing a chemical fingerprint. The data acquisition
      time was 14 hours, thus showing that a clinical time frame of hours rather than
      days has been achieved. 

PMID- 24106739
TI  - Comment on "Partition coefficient measurements in picoliter drops using a
      segmented flow microfluidic device".

PMID- 24106740
TI  - Facile synthesis, self-assembly, and photoelectrical performance of SrTiO3 hollow
      spheres with open holes.
AB  - This paper presents a facile method to synthesize monodisperse SrTiO3 hollow
      spheres with one or two openings through a template-assisted approach. These
      hollow spheres were further self-assembled into densely packed nanofilms at a
      "hexane-water" interface. TEM, SEM, HRTEM, XRD, etc., were employed to
      characterize the morphology and structure of the SrTiO3 hollow spheres as well as
      the corresponding nanofilms. The nanofilm-based photodevice displayed
      considerably higher sensitivity to UV than visible light and dark. 

PMID- 24106741
TI  - Highly uniform hollow GdF3 spheres: controllable synthesis, tuned luminescence,
      and drug-release properties.
AB  - In this paper, uniform hollow mesoporous GdF3 micro/nanospheres were successfully
      prepared by a facile two-step synthesis route without using any surfactant,
      catalyst, and further calcination process. The precursor Gd(OH)CO3 spheres are
      prepared by a coprecipitation process. After that, uniform and size-tunable GdF3
      hollow spheres were easily coprecipitated with NaBF4 at the sacrifice of the
      precursor with low temperature and short reaction time. X-ray diffraction,
      scanning electron microscopy, transmission electron microscopy, high-resolution
      TEM, N2 adsorption/desorption, and up-conversion (UC) photoluminescence spectra
      were used to characterize the as-obtained products. It is found that the initial
      pH value and NaBF4/Gd(3+) molar ratios play important roles in the structures,
      sizes, and phases of the hollow products. The growth mechanism of the hollow
      spheres has been systematically investigated based on the Kirkendall effect.
      Under 980 nm IR laser excitation, UC luminescence of the as-prepared
      Yb(3+)/Er(3+)-codoped GdF3 hollow spheres can be changed by a simple adjustment
      of the concentration of the Yb(3+) ion. Enhanced red emission is obtained by
      introducing Li(+) ions in GdF3:Yb(3+)/Er(3+). Furthermore, a doxorubicin release
      experiment and a 3-[4,5-dimethylthiazol-2-yl]-2,5-diphenyltetrazolium bromide
      cytotoxicity assay reveal that the product has potential application in drug
      delivery and targeted cancer therapy. 

PMID- 24106742
TI  - Approach for chronic total occlusion with intravascular ultrasound-guided reverse
      controlled antegrade and retrograde tracking technique: single center experience.
AB  - BACKGROUND: Controlled antegrade and retrograde subintimal tracking (CART) or
      reverse CART techniques is the final step for percutaneous revascularization of
      coronary chronic total occlusion (CTO), but it still represents technical
      challenges and risk in interventional procedures. OBJECTIVES: Our purpose was to
      utilize intravascular ultrasound (IVUS)-guided reverse CART approach for
      percutaneous revascularization of CTO in our heart center, focusing on its
      safety, efficacy, and latest technical developments. METHODS: From November 2006
      to November 2012, 49 patients with CTO failed to antegrade and/or retrograde
      percutaneous revascularization of CTO from true lumen to true lumen were enrolled
      in and underwent IVUS guided reverse CART approach. RESULTS: The mean J-CTO score
      of cases was 2.5. IVUS guidance was successfully implemented in 95.9%; IVUS
      identified that 61.7% of retrograde wires were located at intimal space, and
      59.5% of antegrade wires were located at subintimal space. A Corsair channel
      dilator was used in 77.6% of cases. The success rates of technique and procedure
      were 95.9% and 93.9%, respectively; the technical minor complications were
      observed in 10.2% of cases, without significant clinic outcomes; 2.0% of cases
      occurred with a major adverse cardiac event of non-ST-elevation myocardial
      infarction; and no case occurred with target vessel revascularization or death.
      The mean length of stent implanted in a single CTO vessel was 51.3 mm. No patient
      appeared with radiation dermatitis and contrast-induced rise of creatinine.
      CONCLUSIONS: IVUS guided reverse CART approach is effective and safe for
      percutaneous revascularization of complex CTO, with a high success and a low
      complication rate. It is feasible to develop this approach for percutaneous
      revascularization of complex CTO. However, suitable case selection and lately
      device handling by experienced operators are the crucial points of success.

PMID- 24106743
TI  - Detection of Stent Underdeployment by StentBoost Imaging.
AB  - OBJECTIVE: To evaluate the additional value of StentBoost(r) (SB), a motion
      corrected X-ray technique that enhances stent visualization, for the assessment
      of stent deployment and procedure optimization during routine percutaneous
      coronary interventions (PCI). BACKGROUND: Underdeployment and malapposition of
      stents during PCI may lead to in-stent thrombosis and restenosis. Coronary
      angiography (CA) is of limited value for the assessment of stent deployment.
      Intravascular ultrasound and optical imaging techniques are the gold standard,
      but are used in <10% of routine PCIs. METHODS: We retrospectively analyzed 260
      coronary lesions treated by stent implantation and assessed by SB during 168
      consecutive PCI procedures. The immediate results of SB analysis and CA were
      assessed by 2 independent interventional cardiologists and compared. RESULTS: A
      total of 275 stents were implanted; 45% were drug-eluting stents (DES). Direct
      stenting was performed in 78%. Results of SB and angiography were concordant for
      210 lesions: 194 stents were correctly deployed (75%) and 16 were underdeployed
      (6%), shown by both techniques. In 47 patients (18%), SB detected an
      underdeployment of the stent whereas the angiographic result was good.
      Postdilatation was performed on the basis of SB in 89% of these cases. The
      additional contribution of SB was higher for left main lesions and for DES, and
      was not affected by coronary calcifications. CONCLUSIONS: This study confirmed
      the usefulness of the stent visualization enhancement technique StentBoost(r) in
      current PCI practice. SB revealed about 20% underdeployed stents not detected by
      CA, and allowed for optimizing PCI by ad hoc effective postdilatation.

PMID- 24106744
TI  - Drug-eluting vs. conventional balloon for side branch dilation in coronary
      bifurcations treated by provisional T stenting.
AB  - OBJECTIVE: The origin of the side branch (SB) is the most common site for
      restenosis in coronary bifurcations. The end-point is to compare the results of
      SB dilation with drug-eluting balloon (DEB group) versus conventional balloon
      (BAL group) in bifurcations treated with provisional T stenting. METHODS AND
      RESULTS: Each group included 50 patients. In DEB, the origin of SB was dilated
      with a Sequent((r)) Please balloon. In both groups, a Taxus Liberte((r)) stent
      was implanted in the main vessel, with kissing balloon postdilation. If the
      outcome for the SB was suboptimal, a Taxus stent was implanted in BAL and a bare
      stent in DEB group. An angiographic follow-up and IVUS were scheduled for 12
      months later. Adverse events (MACE) were 24% in BAL versus 11% in DEB (P = 0.11),
      with greater revascularization (TLR) in the BAL group (22% vs. 12%, P = 0.16). At
      angiographic follow-up, there was a lower percentage of SB restenosis in the DEB
      group (20% vs. 7%, P = 0.08), with less late loss (0.40 mm vs. 0.09 mm, P =
      0.01). CONCLUSION: Side branch dilation with a drug-eluting balloon resulted in
      better angiographic outcomes than with a conventional balloon, with less late
      loss and restenosis at the 12-month follow-up.

PMID- 24106745
TI  - No cardioprotective benefit of ischemic postconditioning in patients with ST
      segment elevation myocardial infarction.
AB  - BACKGROUND: Postconditioning is a potential cardioprotective strategy that has
      demonstrated conflicting and variable reductions in infarct size in human trials.
      OBJECTIVES: To determine whether postconditioning could increase the extent of
      myocardial salvage in patients with acute ST-segment elevation myocardial
      infarction undergoing primary percutaneous coronary intervention (PPCI). METHODS:
      One hundred two patients (aged 57 +/- 11 years; 88% male) were randomly assigned
      to a postconditioning or standard protocol. Cardiovascular magnetic resonance
      imaging was performed 3 days after PPCI to measure the volumetric extent of
      myocardial necrosis and the area at risk. RESULTS: With similar time-to
      reperfusion (170 +/- 84 minutes in the postconditioning group vs. 150 +/- 70
      minutes in the standard group, P = 0.22), the myocardial salvage index was not
      significantly different between the postconditioned group and the control group,
      averaging 42 +/- 22% vs. 33 +/- 21%, respectively (P = 0.08). Furthermore,
      postconditioning was not associated with a smaller infarct size compared to
      controls (13 +/- 7 g/m(2) vs. 15 +/- 8 g/m(2), respectively, P = 0.18).
      CONCLUSIONS: Postconditioning does not significantly increase myocardial salvage
      or reduce infarct size in patients with STEMI undergoing PPCI. However, the
      possibility of a more modest impact of postconditioning cannot be excluded with
      our sample size.

PMID- 24106746
TI  - Morphological findings in typical variant angina presenting as acute coronary
      syndrome using optical coherence tomography.
AB  - BACKGROUND: Coronary vasospasm causes variant angina, as well as acute myocardial
      infarction, ventricular tachycardia, and sudden cardiac death. We evaluated
      morphological changes due to vasospastic lesions, which may cause acute coronary
      syndrome (ACS), using a novel technique called optical coherence tomography
      (OCT). METHODS: Twenty patients (40-83 years old, 19 males) with vasospasm
      induced ACS who visited the emergency room because of continuous chest pain and
      displayed transient ST segment elevation in their electrocardiogram were enrolled
      in the study. None of these patients had significant coronary artery disease and
      all had positive results in the provocation test. OCT examinations were performed
      for evaluation of vasospastic lesions. RESULTS: Intraluminal thrombi and intimal
      erosion were found in 6 (33.3%) and 2 patients (10%), respectively. High
      sensitivity C-reactive protein levels were significantly higher in patients with
      microthrombi (2.66 +/- 3.33 mg/L) compared with those in patients without
      microthrombi (0.49 +/- 0.30 mg/L; P = 0.022). Serum cardiac troponin-I levels
      were not significantly different between patients with or without microthrombi
      (2.37 +/- 5.31 ng/mL vs. 1.45 +/- 4.68 ng/mL; P = 0.704). Other parameters,
      including creatinine kinase-myocardial band isoenzyme, total cholesterol, pain
      duration, residual stenosis, lesion length, and coronary risk factors, were not
      significantly different between the 2 groups. CONCLUSION: In patients with
      vasospasm-induced ACS, microthrombi with or without intimal erosion are major
      abnormal morphologic findings of OCT examinations. However, further large-scale
      studies are required for validation.

PMID- 24106747
TI  - A case of cutaneous angiolipoleiomyoma (angiomyolipoma) in a budgerigar
      (Melopsittacus undulatus).
AB  - We report a case of cutaneous angiolipoleiomyoma (angiomyolipoma) found on the
      anterior wall of the ventral part of the abdomen of a three-year-old female
      budgerigar (Melopsittacus undulatus). Histologic examination of the well
      circumscribed, surgically removed tumour (1.5 cm in diameter) showed a benign
      admixed proliferation of blood vessels of different size, smooth muscle bundles,
      and mature adipose tissue, without evidence of malignancy. Endothelial cells of
      the haemangioma component were positive for claudin-5 endothelium-specific
      immunohistochemical marker, and the leiomyoma component was positive for alpha
      smooth muscle actin. The differentiated lipocytes showed S-100 protein
      positivity. The Ki-67 labelling index was 2 to 3%. The mesenchymal tumour was
      negative for HMB45 melanocytic immunhistochemical marker. To the best of our
      knowledge, this is the first report describing a cutaneous angiolipoleiomyoma in
      a budgerigar with histological and immunohistochemical analyses. 

PMID- 24106749
TI  - Disruption of oligomerization and dehydroalanine formation as mechanisms for ClpP
      protease inhibition.
AB  - Over 100 protease inhibitors are currently used in the clinics, and most of them
      use blockage of the active site for their mode of inhibition. Among the protease
      drug targets are several enzymes for which the correct multimeric assembly is
      crucial to their activity, such as the proteasome and the HIV protease. Here, we
      present a novel mechanism of protease inhibition that relies on active-site
      directed small molecules that disassemble the protease complex. We show the
      applicability of this mechanism within the ClpP protease family, whose members
      are tetradecameric serine proteases and serve as regulators of several cellular
      processes, including homeostasis and virulence. Compound binding to ClpP in a
      substoichiometric fashion triggers the formation of completely inactive
      heptamers. Moreover, we report the selective beta-sultam-induced dehydroalanine
      formation of the active site serine. This reaction proceeds through sulfonylation
      and subsequent elimination, thereby obliterating the catalytic charge relay
      system. The identity of the dehydroalanine was confirmed by mass spectrometry and
      crystallography. Activity-based protein profiling experiments suggest the
      formation of a dehydroalanine moiety in living S. aureus cells upon beta-sultam
      treatment. Collectively, these findings extend our view on multicomponent
      protease inhibition that until now has mainly relied on blockage of the active
      site or occupation of a regulatory allosteric site. 

PMID- 24106748
TI  - Prescription coverage in indigent patients affects the use of long-acting opioids
      in the management of cancer pain.
AB  - PURPOSE: We tested the hypothesis that prescription coverage affects the
      prescribing of long-acting opiates to indigent inner city minority patients with
      cancer pain. MATERIALS AND METHODS: We conducted a chart review of 360 patients
      treated in the Oncology Practice at University of Medicine and Dentistry of New
      Jersey University Hospital, who were prescribed opiate pain medications. Half the
      patients were charity care or self-pay (CC/SP), without the benefit of
      prescription coverage, and half had Medicaid, with unlimited prescription
      coverage. We evaluated patients discharged from a hospitalization, who had three
      subsequent outpatient follow-up visits. We compared demographics, pain intensity,
      the type and dose of opiates, adherence to prescribed pain regimen, unscheduled
      emergency department visits, and unscheduled hospitalizations. RESULTS: There was
      a significantly greater use of long-acting opiates in the Medicaid group than in
      the CC/SP group. The Medicaid group had significantly more African American
      patients and a greater rate of smoking and substance use, and the CC/SP group
      disproportionately more Hispanic and Asian patients and less smoking and
      substance use. Hispanic and Asian patients were less likely to have long-acting
      opiates prescribed to them. Pain levels and adherence were equivalent in both
      groups and were not affected by any of these variables except stage of disease,
      which was equally distributed in the two groups. CONCLUSION: Appropriate use of
      long-acting opiates for equivalent levels of cancer pain was influenced only by
      the availability of prescription coverage. The group without prescription
      coverage and receiving fewer long-acting opiates had disproportionately more
      Hispanic and Asian patients.

PMID- 24106750
TI  - In vitro and in vivo effects of (-)-epigallocatechin 3-O-gallate on Leishmania
      amazonensis.
AB  - (-)-Epigallocatechin 3-O-gallate (1), the most abundant flavanol in green tea,
      has been reported to have antiproliferative effects on Trypanosoma cruzi. The
      present study reports the effects in vitro and in vivo of 1 on Leishmania
      amazonensis. L. amazonensis-infected macrophages treated with 1 exhibited a
      significant reduction of the infection index in a dose-dependent manner, with an
      IC50 value of 1.6 MUM. Oral administration of 1 on L. amazonensis-infected BALB/c
      mice (30 mg/kg/day) resulted in a decrease in the lesion size and parasite
      burden, without altering serological markers of toxicity. These data demonstrate
      the in vitro and in vivo leishmanicidal effects of compound 1. 

PMID- 24106751
TI  - Omentoplasty to assist perineal defect closure following laparoscopic
      abdominoperineal resection.
AB  - AIM: This technical note describes laparoscopic production of a well
      vascularized, omental flap of adequate size to fill the pelvic floor defect in
      the course of laparoscopic abdominoperineal resection (LAPR). METHOD: The omentum
      is laparoscopically mobilized and transposed to the pelvis following full LAPR in
      three discrete stages. RESULTS: Laparoscopic omental mobilization, transfer and
      buttressing of a primary perineal repair reduces pelvic dead space and
      facilitates closure following LAPR with minimal additional operative time or
      complications and a potential reduction in perineal wound associated morbidity.
      CONCLUSION: Laparoscopic omental mobilization is technically feasible and
      provides a safe method to aid perineal wound closure.

PMID- 24106753
TI  - Intermolecular interaction as the origin of red shifts in absorption spectra of
      zinc-phthalocyanine from first-principles.
AB  - We investigate electronic origins of a redshift in absorption spectra of a
      dimerized zinc phthalocyanine molecule (ZnPc) by means of hybrid density
      functional theoretical calculations. In terms of the molecular orbital (MO)
      picture, the dimerization splits energy levels of frontier MOs such as the
      highest occupied molecular orbital (HOMO) and the lowest unoccupied molecular
      orbital (LUMO) of the constituent molecules. Consequently, the absorption
      wavelength seems to become longer than the monomer as the overlap between the
      monomers becomes larger. However, for a ZnPc dimer configuration with its
      cofacially stacked monomer arrangement, the calculated absorption spectra within
      the time-dependent density functional theory indicates no redshift but blueshift
      in the Q-band absorption spectrum, i.e., a typical H-aggregate. The origin of the
      apparently contradictory result is elucidated by the conventional description of
      the interaction between monomer transition dipoles in molecular dimers [Kasha, M.
      Radiat. Res. 1963, 20, 55]. The redshift is caused by an interaction between the
      two head-to-tail transition dipoles of the monomers, while the side-by-side
      arranged transition dipoles result in a blueshift. By tuning the dipole-dipole
      interaction based on the electronic natures of the HOMO and the LUMO, we describe
      a slipped-stacked ZnPc dimer configuration in which the Q-band absorption
      wavelength increases by as large as 144 nm relative to the monomer Q-band. 

PMID- 24106754
TI  - Mammographic density in birth cohorts of Danish women: a longitudinal study.
AB  - BACKGROUND: Breast cancer is the leading malignant disease among western women
      with incidence increasing over time. High mammographic density is a well
      established risk factor for breast cancer. We explored trends in mammographic
      density across birth cohorts to gain further insight into possible time trends in
      women's mammographic density that might explain the historical increase in breast
      cancer incidence. METHODS: Data derived from two mammography screening programs
      in Denmark from 1991 to 2001, including on average 41,091 women from Copenhagen
      and 52,938 women from Funen aged 50-69. Mammographic density was assessed
      qualitatively (fatty or mixed/dense) by senior screening radiologists. The
      proportion of women with mixed/dense mammographic density was calculated by age
      at screening, screening period, and birth cohort. The Generalized Estimating
      Equations were used to calculate odds ratios and 95% confidence intervals. All
      statistical tests were two-sided. RESULTS: The proportion of women with
      mixed/dense mammographic density increased from 45% among women born in the 1920s
      to 75-80% among women born in the 1940s. In Copenhagen, the age-adjusted odds
      ratio (95% CI) of mixed/dense mammographic density in women born in 1941-42 was
      2.48 (2.22-2.76) compared with women born in 1921-22. In Funen, the age-adjusted
      odds ratio of mixed/dense mammographic density in women born in 1946-47 was 5.89
      (5.32-6.51) compared with women born in 1924-25. Hormone use had a greater impact
      on mammographic density in birth cohorts of the 1920s compared with those of the
      1940s. CONCLUSIONS: We found suggestive evidence of a birth cohort pattern in
      mammographic density and an attenuated impact of hormone use in younger compared
      with older birth cohorts suggesting that postmenopausal mammographic density
      could be linked to changing exposures accumulated over time in women's lives.

PMID- 24106755
TI  - Use of transcriptome sequencing to understand the pistillate flowering in hickory
      (Carya cathayensis Sarg.).
AB  - BACKGROUND: Different from herbaceous plants, the woody plants undergo a long
      period vegetative stage to achieve floral transition. They then turn into
      seasonal plants, flowering annually. In this study, a preliminary model of gene
      regulations for seasonal pistillate flowering in hickory (Carya cathayensis) was
      proposed. The genome-wide dynamic transcriptome was characterized via the joint
      approach of RNA sequencing and microarray analysis. RESULTS: Differential
      transcript abundance analysis uncovered the dynamic transcript abundance patterns
      of flowering correlated genes and their major functions based on Gene Ontology
      (GO) analysis. To explore pistillate flowering mechanism in hickory, a
      comprehensive flowering gene regulatory network based on Arabidopsis thaliana was
      constructed by additional literature mining. A total of 114 putative flowering or
      floral genes including 31 with differential transcript abundance were identified
      in hickory. The locations, functions and dynamic transcript abundances were
      analyzed in the gene regulatory networks. A genome-wide co-expression network for
      the putative flowering or floral genes shows three flowering regulatory modules
      corresponding to response to light abiotic stimulus, cold stress, and
      reproductive development process, respectively. Totally 27 potential flowering or
      floral genes were recruited which are meaningful to understand the hickory
      specific seasonal flowering mechanism better. CONCLUSIONS: Flowering event of
      pistillate flower bud in hickory is triggered by several pathways synchronously
      including the photoperiod, autonomous, vernalization, gibberellin, and sucrose
      pathway. Totally 27 potential flowering or floral genes were recruited from the
      genome-wide co-expression network function module analysis. Moreover, the
      analysis provides a potential FLC-like gene based vernalization pathway and an
      'AC' model for pistillate flower development in hickory. This work provides an
      available framework for pistillate flower development in hickory, which is
      significant for insight into regulation of flowering and floral development of
      woody plants.

PMID- 24106756
TI  - Clinical profile of recurrent community-acquired pneumonia in children.
AB  - BACKGROUND: The aim of this case-control study was to analyse the clinical
      characteristics of children with recurrent community-acquired pneumonia (rCAP)
      affecting different lung areas (DLAs) and compare them with those of children who
      have never experienced CAP in order to contribute to identifying the best
      approach to such patients. METHODS: The study involved 146 children with >=2
      episodes of radiographically confirmed CAP in DLA in a single year (or >=3
      episodes in any time frame) with radiographic clearing of densities between
      occurrences, and 145 age- and gender-matched controls enrolled in Milan, Italy,
      between January 2009 and December 2012. The demographic and clinical
      characteristics of the cases and controls were compared, and a comparison was
      also made between the cases with rCAP (i.e. <=3 episodes) and those with highly
      recurrent CAP (hrCAP: i.e. >3 episodes). RESULTS: Gestational age at birth (p =
      0.003), birth weight (p = 0.006), respiratory distress at birth (p < 0.001), and
      age when starting day care attendance (p < 0.001) were significantly different
      between the cases and controls, and recurrent infectious wheezing (p < 0.001),
      chronic rhinosinusitis with post-nasal drip (p < 0.001), recurrent upper
      respiratory tract infections (p < 0.001), atopy/allergy (p < 0.001) and asthma (p
      < 0.001) were significantly more frequent. Significant risk factors for hrCAP
      were gastroesophageal reflux disease (GERD; p = 0.04), a history of atopy and/or
      allergy (p = 0.005), and a diagnosis of asthma (p = 0.0001) or middle lobe
      syndrome (p = 0.001). Multivariate logistic regression analysis, adjusted for age
      and gender, showed that all of the risk factors other than GERD and wheezing were
      associated with hrCAP. CONCLUSIONS: The diagnostic approach to children with rCAP
      in DLAs is relatively easy in the developed world, where the severe chronic
      underlying diseases favouring rCAP are usually identified early, and patients
      with chronic underlying disease are diagnosed before the occurrence of rCAP in
      DLAs. When rCAP in DLAs does occur, an evaluation of the patients' history and
      clinical findings make it possible to limit diagnostic investigations.

PMID- 24106757
TI  - Whitening effect of Sophora flavescens extract.
AB  - CONTEXT: Sophora flavescens Ait. (Leguminosae) has been proposed as a new
      whitening agent for cosmetics, because it has a strong ability to inhibit
      tyrosinase, a key enzyme in the formation of melanin. OBJECTIVE: We conducted a
      study to determine whether ethanol extract of the roots of S. flavescens has the
      potential for use as a whitening cosmetic agent by investigating its underlying
      mechanisms of action. MATERIALS AND METHODS: To elucidate the mechanism of action
      of S. flavescens extract, we used DNA microarray technology. We investigated the
      changes in the mRNA levels of genes associated with the formation and transport
      of melanosomes. We also identified the formation and transport of melanosomes
      with immunohistochemistry and immunofluorescence analyses. Finally, the skin
      whitening effect in vivo of S. flavescens extract was analyzed on human skin.
      RESULTS: We found that S. flavescens extract strongly inhibited tyrosinase
      activity (IC50, 10.4 MUg/mL). Results also showed that key proteins involved in
      the formation and transport of melanosomes were dramatically downregulated at
      both mRNA and protein level in keratinocytes exposed to S. flavescens extract. In
      addition, a clinical trial of a cream containing 0.05% S. flavescens extract on
      human skin showed it had a significant effect on skin whitening by mechanical and
      visual evaluation (1.14-fold). DISCUSSION AND CONCLUSION: This study provides
      important clues toward understanding the effects of S. flavescens extract on the
      formation and transport of melanosomes. From these results, we suggest that
      naturally occurring S. flavescens extract might be useful as a new whitening
      agent in cosmetics.

PMID- 24106758
TI  - Discrimination of Swiss cheese from 5 different factories by high impact volatile
      organic compound profiles determined by odor activity value using selected ion
      flow tube mass spectrometry and odor threshold.
AB  - Swiss cheese contains more than 200 volatile organic compounds (VOCs). Gas
      chromatography-mass spectrometry has been utilized for the analysis of volatile
      compounds in food products; however, it is not sensitive enough to measure VOCs
      directly in the headspace of a food at low concentrations. Selected ion flow tube
      mass spectrometry (SIFT-MS) provides a basis for determining the concentrations
      of VOCs in the head space of the sample in real time at low concentration levels
      of parts per billion/trillion by volume. Of the Swiss cheese VOCs, relatively few
      have a major impact on flavor quality. VOCs with odor activity values (OAVs)
      (concentration/odor threshold) greater than one are considered high-impact flavor
      compounds. The objective of this study was to utilize SIFT-MS concentrations in
      conjunction with odor threshold values to determine OAVs thereby identifying high
      impact VOCs to use for differentiating Swiss cheese from five factories and
      identify the factory variability. Seventeen high-impact VOCs were identified for
      Swiss cheese based on an OAV greater than one in at least 1 of the 5 Swiss cheese
      factories. Of these, 2,3-butanedione was the only compound with significantly
      different OAVs in all factories; however, cheese from any pair of factories had
      multiple statistically different compounds based on OAV. Principal component
      analysis using soft independent modeling of class analogy statistical
      differentiation plots, with all of the OAVs, showed differentiation between the 5
      factories. Overall, Swiss cheese from different factories was determined to have
      different OAV profiles utilizing SIFT-MS to determine OAVs of high impact
      compounds. 

PMID- 24106760
TI  - Celebrating the past 75 years and preparing for the next 75 years.

PMID- 24106762
TI  - Detection of Clostridium tyrobutyricum in milk to prevent late blowing in cheese
      by automated ribosomal intergenic spacer analysis.
AB  - Clostridium tyrobutyricum has been identified as the main causal agent of the
      late blowing defect in cheese, with major effects on quality and commercial
      value. In this work, for the first time, we applied automated ribosomal
      intergenic spacer analysis (ARISA) approach to diagnose the presence of C.
      tyrobutyricum in raw milk before cheesemaking. A species-specific primer set was
      designed and used for this original application of the ARISA. Sensitivity of
      detection, reproducibility of the fluorescent PCR assay, and repeatability of the
      capillary electrophoretic analysis of amplicons were evaluated using DNA
      extracted from milk added with known amounts of C. tyrobutyricum genome copies,
      ranging from 3 * 10(6) to 3. Results indicated that the sensitivity of the
      technique permits to detect the bacterium in all the samples. The
      reproducibility, evaluated by analyzing 3 sets of serial dilutions, resulted
      satisfactory, with little deviation within PCR reactions amplifying the same
      starting amount of template (standard deviations <= 0.1, coefficients of
      variation <= 3%). The peaks' fluorescence displayed an evident correspondence
      with the number of genome copies contained in each dilution. The capillary
      electrophoretic analysis, tested by running a single PCR product per dilution
      point in 10 repeats, resulted efficient and highly repeatable, with excellent
      coefficients of variation <= 2% and standard deviations <= 0.1 in all the sample
      sets. This application of ARISA gives good estimates of the total C.
      tyrobutyricum DNA content allowing a specific, fine-scale resolution of this
      pollutant species in a complex system as milk. A further advantage linked to the
      automatization of the process. 

PMID- 24106759
TI  - Characterization and comparison of the pungent components in commercial
      Zanthoxylum bungeanum oil and Zanthoxylum schinifolium oil.
AB  - In the present study, the characterization and comparison of the pungent
      components in commercial Z. bungeanum oils and Z. schinifolium oils were
      investigated. By high-performance liquid chromatography (HPLC)-mass spectrometry
      (MS/MS) analysis, the major alkylamides in Z. bungeanum and Z. schinifolium oils
      were identified as hydroxy-epsilon-sanshool, hydroxy-alpha-sanshool, hydroxy-beta
      sanshool, hydroxy-gamma-sanshool, hydroxy-gamma-isosanshool, bungeanool,
      isobungeanool, and tetrahydrobungeanool, respectively. Hydroxy-alpha-sanshool was
      found to be the most abundant alkylamide in all oils. The levels of hydroxy
      epsilon-sanshool and hydroxy-beta-sanshool in Z. bungeanum oils were comparable
      to that in Z. schinifolium oils, whereas Z. bungeanum oils contained
      significantly (P less than 0.05) higher levels of hydroxy-gamma-isosanshool,
      bungeanool, isobungeanool, and tetrahydrobungeanool, compared with Z.
      schinifolium oils. Furthermore, principal component analysis (PCA) indicated that
      Z. bungeanum oil and Z. schinifolium oil were clearly classified by HPLC
      fingerprinting profiles and concentrations of alkylamides. In addition, the
      results of PCA suggested that alkylamides, such as hydroxy-gamma-sanshool and
      bungeanool, could be potential markers to distinguish Z. bungeanum oil and Z.
      schinifolium oil. The results from this study could be used to discriminate the
      different flavor characterization and control the quality of commercial Z.
      bungeanum oil and Z. schinifolium oil. 

PMID- 24106763
TI  - Sensory evaluation and electronic tongue for sensing flavored mineral water taste
      attributes.
AB  - In this article a trained sensory panel evaluated 6 flavored mineral water
      samples. The samples consisted of 3 different brands, each with 2 flavors (pear
      lemon grass and josta berry). The applied sensory method was profile analysis.
      Our aim was to analyze the sensory profiles and to investigate the similarities
      between the sensitivity of the trained human panel and an electronic tongue
      device. Another objective was to demonstrate the possibilities for the prediction
      of sensory attributes from electronic tongue measurements using a multivariate
      statistical method (Partial Least Squares regression [PLS]). The results showed
      that the products manufactured under different brand name but with the same
      aromas had very similar sensory profiles. The panel performance evaluation showed
      that it is appropriate (discrimination ability, repeatability, and panel
      consensus) to compare the panel's results with the results of the electronic
      tongue. The samples can be discriminated by the electronic tongue and an accurate
      classification model can be built. Principal Component Analysis BiPlot diagrams
      showed that Brand A and B were similar because the manufacturers use the same
      aroma brands for their products. It can be concluded that Brand C was quite
      different compared to the other samples independently of the aroma content. Based
      on the electronic tongue results good prediction models can be obtained with high
      correlation coefficient (r(2) > 0.81) and low prediction error (RMSEP < 13.71 on
      the scale of the sensory evaluation from 0 to 100). 

PMID- 24106764
TI  - Clarifying the role of psychological pain in the risks of suicidal ideation and
      suicidal acts among patients with major depressive episodes.
AB  - The role of psychological pain in the risk of suicide was explored using a three
      dimensional psychological pain model (pain arousal, painful feelings, pain
      avoidance). The sample consisted of 111 outpatients with major depressive
      episodes, including 28 individuals with suicidal histories. They completed the
      Chinese version of the Beck Scale for Suicide Ideation (BSI), the Beck Depression
      Inventory (BDI), the Psychache Scale, and the three-dimensional Psychological
      Pain Scale (TDPPS). A structured clinical interview was conducted to assess the
      history of suicidal acts. Significant correlations were found among BDI, BSI, and
      TDPPS scores (p < .01). Stepwise regression analyses showed that only pain
      avoidance scores significantly predicted suicide ideation at one's worst point
      (beta = .79, p < .001) and suicidal acts (beta = .46, p < .001). Pain avoidance
      was also a better predictor of current suicidal ideation (beta = .37, p = .001)
      than were BDI scores (beta = .31, p < .01). Increased levels of pain avoidance
      during a major depressive episode may be a dominant component of the motivation
      for suicide. Future clinical assessments for populations at high risk of suicide
      should include measures of psychological pain to reduce the incidence of suicide.

PMID- 24106767
TI  - Structure and secretion of CofJ, a putative colonization factor of
      enterotoxigenic Escherichia coli.
AB  - Enterotoxigenic Escherichia coli (ETEC) colonize the human gut, causing severe
      cholera-like diarrhoea. ETEC utilize a diverse array of pili and fimbriae for
      host colonization, including the Type IVb pilus CFA/III. The CFA/III pilus
      machinery is encoded on the cof operon, which is similar in gene sequence and
      synteny to the tcp operon that encodes another Type IVb pilus, the Vibrio
      cholerae toxin co-regulated pilus (TCP). Both pilus operons possess a syntenic
      gene encoding a protein of unknown function. In V. cholerae, this protein, TcpF,
      is a critical colonization factor secreted by the TCP apparatus. Here we show
      that the corresponding ETEC protein, CofJ, is a soluble protein secreted via the
      CFA/III apparatus. We present a 2.6 A resolution crystal structure of CofJ,
      revealing a large beta-sandwich protein that bears no sequence or structural
      homology to TcpF. CofJ has a cluster of exposed hydrophobic side-chains at one
      end and structural homology to the pore-forming proteins perfringolysin O and
      alpha-haemolysin. CofJ binds to lipid vesicles and epithelial cells, suggesting a
      role in membrane attachment during ETEC colonization. 

PMID- 24106768
TI  - Associations of novel adipocytokines with bone biomarkers in intra uterine growth
      restricted fetuses/neonates at term.
AB  - OBJECTIVE: To prospectively investigate the potential associations of the novel
      adipocytokines resistin, apelin and visfatin (recently implicated in bone
      metabolism) with bone biomarkers in fetal and neonatal blood from intra uterine
      growth restricted (IUGR, associated with low bone mass at birth) and appropriate
      for gestational age (AGA) pregnancies. METHODS: Circulating concentrations of
      resistin, apelin and visfatin were correlated with concentrations of markers of
      bone formation [osteocalcin (OC), bone-specific alkaline phosphatase (BALP)] and
      resorption [osteoprotegerin (OPG), soluble receptor activator of nuclear factor
      kappaB ligand (sRANKL) and cross-linked N-telopeptide of type I collagen (NTx)]
      in 20 IUGR and 20 AGA full-term fetuses and neonates on postnatal day 1-(N1) and
      4-(N4). RESULTS: In the AGA group, fetal resistin and N1 visfatin concentrations
      negatively correlated with respective NTx ones (r >= -0.472, p <= 0.036 in both
      cases). In the IUGR group, fetal and N4 resistin concentrations negatively
      correlated with sRANKL concentrations (r >= -0.583, p <= 0.007 in both cases).
      Furthermore, fetal apelin and visfatin concentrations positively correlated with
      fetal BALP ones (r >= 0.471, p <= 0.042, in both cases). CONCLUSIONS: All three
      adipocytokines may exert a positive effect on fetal/neonatal bone metabolism,
      either by inhibiting bone resorption or promoting bone formation in both normal
      and IUGR pregnancies. Although the mechanisms behind these correlations are
      unclear, a modulation of perinatal bone metabolism by these adipocytokines may be
      suggested.

PMID- 24106769
TI  - A distinct group of CpG islands shows differential DNA methylation between
      replicas of the same cell line in vitro.
AB  - BACKGROUND: CpG dinucleotide-rich genomic DNA regions, known as CpG islands
      (CGIs), can be methylated at their cytosine residues as an epigenetic mark that
      is stably inherited during cell mitosis. Differentially methylated regions (DMRs)
      are genomic regions showing different degrees of DNA methylation in multiple
      samples. In this study, we focused our attention on CGIs showing different DNA
      methylation between two culture replicas of the same cell line. RESULTS: We used
      methylation data of 35 cell lines from the Encyclopedia of DNA Elements (ENCODE)
      consortium to identify CpG islands that were differentially methylated between
      replicas of the same cell line and denoted them Inter Replicas Differentially
      Methylated CpG islands (IRDM-CGIs). We identified a group of IRDM-CGIs that was
      consistently shared by different cell lines, and denoted it common IRDM-CGIs. X
      chromosome CGIs were overrepresented among common IRDM-CGIs. Autosomal IRDM-CGIs
      were preferentially located in gene bodies and intergenic regions had a lower G +
      C content, a smaller mean length, and a reduced CpG percentage. Functional
      analysis of the genes associated with autosomal IRDM-CGIs showed that many of
      them are involved in DNA binding and development. CONCLUSIONS: Our results show
      that several specific functional and structural features characterize common IRDM
      CGIs. They may represent a specific subset of CGIs that are more prone to being
      differentially methylated for their intrinsic characteristics.

PMID- 24106770
TI  - "Unique trend" and "contradictory trend" in discrimination of primary synchronous
      lung cancer and metastatic lung cancer.
AB  - BACKGROUND: Distinguishing between multiple primary lung cancers and metastatic
      tumors is often difficult when the tumor histology is same. Since genomic
      instability is a common feature of cancer, we hypothesized that independently
      arising neoplasms in an individual patient would exhibit measurable genomic
      variation, enabling discrimination of tumor lineage and relatedness. The
      feasibility of analyzing genomic instability expression profiles to distinguish
      multiple primary lung cancers from metastatic tumors was evaluated. METHODS: This
      study enrolled 13 patients, with multiple primary lung cancers demonstrating with
      the histology, who underwent surgery between April 2003 and December 2012 at the
      Department of the Thoracic Surgery at West China Hospital in Sichuan province of
      China and 10 patients who were diagnosed as metastasis disease during the same
      period for comparison purposes. Genomic DNA from lung cancers from individual
      patients was analyzed by six microsatellites (D2S1363, D6S1056, D7S1824,
      D10S1239, D15S822, and D22S689) with PCR to identify discordant allelic
      variation. The experiments were approved by the West China Hospital Ethics
      committee (No.2013 (33)) and all patients agreed to participate in the study and
      signed an informed consent form. RESULTS: All of the 10 patients with distant
      metastasis showed a consistent consequence that we called "unique trend" between
      primary tumor and distant metastasis. The "trend" is representive in this study,
      which means that all alleles corresponding to six microsatellite markers were
      detected in DNA from primary tumors but were reduced or not observed in DNA from
      metastatic tumors. In the group of synchronous lung tumor with different
      histological types, the result showed a "contradictory trend". Some alleles were
      detected in DNA from primary tumors but were reduced or not observed in DNA from
      metastatic tumors and other alleles corresponding to six microsatellite markers
      were detected in DNA from metastatic tumors but were reduced or not observed in
      DNA from primary tumors. In the third group (synchronous lung tumor with same
      histological types), 2 of 8 patients showed "unique trend" and the others showed
      "contradictory trend". CONCLUSIONS: With polymorphic microsatellite markers, the
      "unique trend" that represents metastasis cancers and the "contradictory trend"
      that represents primary multiple tumors are useful in the diagnosis between
      tumors found at the same time in the pulmonary even diagnosed with the
      histopathological evaluation from a single patient.

PMID- 24106771
TI  - Implementation of specific strength training among industrial laboratory
      technicians: long-term effects on back, neck and upper extremity pain.
AB  - BACKGROUND: Previous studies have shown positive effects of physical exercise at
      the workplace on musculoskeletal disorders. However, long-term adherence remains
      a challenge. The present study evaluates long-term adherence and effects of a
      workplace strength training intervention on back, neck and upper extremity pain
      among laboratory technicians. METHODS: Cluster-randomized controlled trial
      involving 537 industrial laboratory technicians. Subjects were randomized at the
      cluster level to one of two groups: training group 1 (TG1, n = 282) performing
      supervised strength training from February to June 2009 (round one) or training
      group 2 (TG2, n = 255) performing supervised strength training from August to
      December 2009 (round two). The outcome measures were changes in self-reported
      pain intensity (0-9) in the back, neck and upper extremity as well as Disability
      of the Arm, Shoulder and Hand (DASH, 0-100). RESULTS: Regular adherence, defined
      as at least one training session per week, was achieved by around 85% in both
      groups in the supervised training periods. In the intention-to-treat analyses
      there were significant group by time effects for pain in the neck, right
      shoulder, right hand and lower back and DASH-resulting in significant reductions
      in pain (mean 0.3 to 0.5) and DASH (mean 3.9) in the scheduled training group
      compared to the reference group. For TG1 there were no significant changes in
      pain in round two, i.e. they maintained the pain reduction achieved in round one.
      Subgroup analyses among those with severe pain (> = 3 on a scale of 0-9) showed a
      significant group by time effect for pain in the neck, right shoulder, upper back
      and lower back. For these subgroups the pain reduction in response to training
      ranged from 1.1 to 1.8. CONCLUSIONS: Specific strength training at the workplace
      can lead to significant long-term reductions in spinal and upper extremity pain
      and DASH. The pain reductions achieved during the intensive training phase with
      supervision appears to be maintained a half year later.

PMID- 24106772
TI  - The effects of different doses of estradiol (E2) on cerebral ischemia in an in
      vitro model of oxygen and glucose deprivation and reperfusion and in a rat model
      of middle carotid artery occlusion.
AB  - BACKGROUND: Because neuroprotective effects of estrogen remain controversial, we
      aimed to investigate the effect of different doses of estradiol (E2) on cerebral
      ischemia using both in vivo and in vitro experiments. RESULTS: PC12 cells were
      cultured at physiological (10 nM and 20 nM) or pharmacological (10 MUM and 20
      MUM) dosages of E2 for 24 hours (h). The results of 5-bromodeoxyuridine (Brdu)
      incorporation and flow cytometric analysis showed that physiological doses of E2
      enhanced cell proliferation and pharmacological doses of E2 inhibited cell
      proliferation. After the cells were exposed to oxygen and glucose deprivation
      (OGD) for 4 h and reperfusion for 20 h, the results of 3-(4, 5-dimethylthiazol-2
      yl) 2, 5-diphenyl tetrazolium bromide (MTT) assay, lactate dehydrogenase (LDH)
      release assay, flow cytometric analysis and Western blot analysis showed that
      physiological doses of E2 enhanced cell viability, reduced cell apoptosis and
      decreased the expression of pro-apoptotic protein caspase-3. In contrast,
      pharmacological doses of E2 decreased cell viability and induced cell apoptosis.
      In vivo, adult ovariectomized (OVX) female rats received continuous subcutaneous
      injection of different doses of E2 for 4 weeks. Transient cerebral ischemia was
      induced for 2 h using the middle cerebral artery occlusion (MCAO) technique,
      followed by 22 h of reperfusion. The results of Garcia test, 2, 3, 5
      triphenyltetrazolium chloride (TTC) staining showed that 6 MUg/kg and 20 MUg/kg
      E2 replacement induced an increase in neurological deficit scores, a decrease in
      the infarct volume and a reduction in the expression of caspase-3 when compared
      to animals in the OVX group without E2 treatment. However, 50 MUg/kg E2
      replacement treatment decreased neurological deficit scores, increased the
      infarct volume and the expression of caspase-3 when compared to animals in the
      control group and 6 up/kg or 20 MUg/kg E2 replacement group. CONCLUSION: We
      conclude that physiological levels of E2 exhibit neuroprotective effects on
      cerebral ischemia; whereas, pharmacological or supraphysiological doses of E2
      have damaging effects on neurons after cerebral ischemia.

PMID- 24106773
TI  - Fruit and vegetable intake and vitamins C and E are associated with a reduced
      prevalence of cataract in a Spanish Mediterranean population.
AB  - BACKGROUND: Cataract is among the major causes of vision impairment and blindness
      worldwide. Epidemiological studies support the role of antioxidants in the
      etiology of cataract, but the evidence for one specific antioxidant over another
      is inconsistent. Few studies have examined the association of cataract with fruit
      and vegetable intake with inconclusive results. In the present study, the
      relationship between cataract and fruit and vegetable intake and dietary and
      blood levels of carotenoids, vitamins C and E were examined in a Spanish
      Mediterranean population. METHODS: The present work is an analysis of data from
      599 elderly ( >= 65 years) participants from the Spanish segment of the EUREYE
      study. This is a European multi-center cross-sectional population-based study.
      Cataract was diagnosed using a slit-lamp examination and defined as any lens
      opacity in either eye or evidence of its removal (cataract extraction). Energy
      adjusted intake of fruit and vegetables and antioxidant vitamins was estimated
      using a semi-quantitative food frequency questionnaire. Plasma concentrations of
      vitamin C were analyzed by a colorimetric method and carotenoids and alpha
      tocopherol by a HPLC method. The associations between cataract and quartiles of
      fruit and vegetable intake and plasma antioxidants were investigated using
      logistic regression models. RESULTS: Of the 599 elderly recruited, 433 (73%) had
      cataract or cataract extraction, 54% were women and 46% were men. After
      adjustments, increasing quartiles of combined fruit and vegetable intake were
      associated with decreasing reduction of odds of cataract or cataract extraction,
      (P for trend = 0.008). Increasing quartiles of dietary intakes from 107 mg/d of
      vitamin C showed a significant decreasing association with prevalence of cataract
      or cataract extraction (P for trend = 0.047). For vitamin E, a protective
      association was found from intakes from 8 mg/d, but no linear trend was observed
      across quartiles of intake (P for trend = 0.944). CONCLUSIONS: High daily intakes
      of fruit and vegetables and vitamins C and E were associated with a significantly
      decreased of the prevalence of cataract or cataract surgery. This study
      reinforces the WHO recommendations on the benefits of diets rich in fruit and
      vegetables.

PMID- 24106774
TI  - Correlation between the prevalence of herniation pits and the alpha angle of the
      hip: computed tomography evaluation in healthy Chinese adults.
AB  - BACKGROUND: Herniation pits (HPs) commonly develop over time at the femoral head
      neck junction in adults, but their cause is still under debate. The purpose of
      study reported here was to investigate the correlation between the prevalence of
      HPs of the femoral neck and the alpha angle of the hips of healthy Chinese
      adults, by using computed tomography (CT). METHODS: Six hundred and seventy
      Chinese adults (representing 1145 hips) who had no known diseases affecting the
      proximal femur and had no symptoms of femoroacetabular impingement underwent a 64
      slice CT scan for medical purposes that included the hip in the scan range. Their
      CT data were analyzed for the prevalence of HPs in the femoral necks and for hip
      alpha angles. RESULTS: The overall prevalence of femoral-neck HPs was 12.5% (143
      of 1145 hips). The prevalence in the left versus right femoral necks was 12.1%
      (69 of 569 hips) versus 12.8% (74 of 576 hips). There was no statistically
      significant difference between the two sides (chi2 = 0.136; p = 0.712). The
      prevalence of HPs was greater in men than in women (15.9% vs 7.7%; p < 0.01) and
      greater in adults older than 30 years than in adults younger than 30 years (chi2=
      14.547; p < 0.01). The alpha angles were greater in the 143 proximal femora with
      HPs than in the 1002 without pits (39.95 degrees  +/- 6.01 degrees  vs 37.97
      degrees  +/- 5.14 degrees ; p < 0.01). CONCLUSIONS: The prevalence of HPs of the
      femoral neck in healthy adults was 12.5%, and the prevalence was greater in men
      than in women. There is a correlation between the prevalence of HPs and the
      contour of the femoral head-neck junction. The formation of pits may be
      attributed to the combination of degeneration and morphologic variances in the
      femoral head-neck junction.

PMID- 24106775
TI  - Teri Mills: champion for America's nurse.

PMID- 24106781
TI  - Enantio- and regioselective CuH-catalyzed hydroamination of alkenes.
AB  - A highly enantio- and regioselective copper-catalyzed hydroamination reaction of
      alkenes has been developed using diethoxymethylsilane and esters of
      hydroxylamines. The process tolerates a wide variety of substituted styrenes,
      including trans-, cis-, and beta,beta-disubstituted styrenes, to yield alpha
      branched amines. In addition, aliphatic alkenes coupled to generate exclusively
      the anti-Markovnikov hydroamination products. 

PMID- 24106782
TI  - Prone versus supine lasix renal scan to assess surgical success after
      laparoscopic and robot-assisted pyeloplasty.
AB  - PURPOSE: Success after laparoscopic pyeloplasty (LP) for ureteropelvic junction
      obstruction is determined based on renal scan (RS) results and patient symptoms
      +/- ultrasonography. The upright or prone position during RS may facilitate
      drainage. This study reports on outcomes after LP and robot-assisted pyeloplasty
      (RALP) and determines if patient position (supine vs prone) alters the results of
      the postoperative RS and surgical "success." PATIENTS AND METHODS: A
      retrospective review of LP and RALP performed by one surgeon between 2005 and
      2012 was performed. Follow-up consisted of RS +/- ultrasonography. The paired t
      test was used to assess for a significant difference between mean T1/2 for supine
      vs prone scans in each patient. Linear regression was used to determine if
      preoperative split renal function on the affected side or degree of preoperative
      hydronephrosis predicted difference in supine vs prone T1/2. RESULTS: There were
      11 LP and 81 RALP performed; 84 had follow-up data. There were four (4.3%)
      failures. Thirty-eight patients had sufficient supine and prone RS for analysis.
      The difference in T1/2 between supine and prone RS was significant (mean
      difference 10.18 +/- 27.28 min, P = 0.03). Strict success increased to 65.8% from
      44.7% and combined strict plus technical success increased to 78.9% from 63.1% on
      prone vs supine RS. Split function and degree of hydronephrosis were not
      predictors of difference in RS results. CONCLUSIONS: LP and RALP have good
      technical results. Prone position for RS may facilitate drainage and may be a
      more accurate representation of postoperative outcome after pyeloplasty,
      particularly in equivocal cases.

PMID- 24106783
TI  - Improving ice nucleation activity of zein film through layer-by-layer deposition
      of extracellular ice nucleators.
AB  - Zein protein has been of scientific interest in the development of biodegradable
      functional food packaging. This study aimed at developing a novel zein-based
      biopolymer film with ice nucleation activity through layer-by-layer deposition of
      biogenic ice nucleators, that is, extracellular ice nucleators (ECINs) isolated
      from Erwinia herbicola , onto zein film surface. The adsorption behaviors and
      mechanisms were investigated using quartz crystal microbalance with dissipation
      monitoring (QCM-D). On unmodified zein surface, the highest ECINs adsorption
      occurred at pH 5.0; on UV/ozone treated zein surface followed by deposition of
      poly(diallyldimethylammonium chloride) (PDADMAC) layer, the optimum condition for
      ECINs adsorption occurred at pH 7.0 and I 0.05 M, where the amount of ECINs
      adsorbed was also higher than that on unmodified zein surface. QCM-D analyses
      further revealed a two-step adsorption process on unmodified zein surfaces,
      compared to a one-step adsorption process on PDADMAC-modified zein surface. Also,
      significantly, in order to quantify the ice nucleation activity of ECINs-coated
      zein films, an empirical method was developed to correlate the number of ice
      nucleators with the ice nucleation temperature measured by differential scanning
      calorimetry. Calculated using this empirical method, the highest ice nucleation
      activity of ECINs on ECINs-modified zein film reached 64.1 units/mm(2), which was
      able to elevate the ice nucleation temperature of distilled water from -15.5 
      degrees C to -7.3  degrees C. 

PMID- 24106784
TI  - Wood as construction material: a "common" choice for carbon management?

PMID- 24106785
TI  - Effect of sodium ions on RNA duplex stability.
AB  - The standard sodium concentration for RNA optical melting experiments is 1.021 M.
      Algorithms that predict Tm, DeltaG degrees 37, and secondary structure from
      sequence generally rely on parameters derived from optical melting experiments
      performed in 1.021 M sodium. Physiological monovalent cation concentrations are
      much lower than 1.021 M. In fact, many molecular biology techniques require
      buffers containing monovalent cation concentrations other than 1.021 M.
      Predictions based on the 1.021 M Na(+) parameters may not be accurate when the
      monovalent cation concentration is not 1.021 M. Here, we report thermodynamic
      data from optical melting experiments for a set of 18 RNA duplexes, each melted
      over a wide range of sodium ion concentrations (71, 121, 221, and 621 mM). Using
      these data and previously published data for the same sequences melted in 1.021 M
      Na(+), we report Tm and DeltaG degrees 37 correction factors to scale the
      standard 1.021 M Na(+) RNA parameters to other sodium ion concentrations. The
      recommended Tm correction factor predicts the melting temperature within 0.7 
      degrees C, and the recommended DeltaG degrees 37 correction factor predicts the
      free energy within 0.14 kcal/mol. These correction factors can be incorporated
      into prediction algorithms that predict RNA secondary structure from sequence and
      provide Tm and DeltaG degrees 37 values for RNA duplexes. 

PMID- 24106786
TI  - Hexadecylamine adsorption at the iron oxide-oil interface.
AB  - The adsorption behavior of a model additive, hexadecylamine, onto an iron surface
      from hexadecane oil has been characterized using polarized neutron reflectometry,
      sum-frequency generation spectroscopy, solution depletion isotherm, and X-ray
      photoelectron spectroscopy (XPS). The amine showed a strong affinity for the
      metal surface, forming a dense monolayer at relatively low concentrations; a
      layer thickness of 16 (+/-3) A at low concentrations, increasing to 20 (+/-3) A
      at greater amine concentrations, was determined from the neutron data. These
      thicknesses suggest that the molecules in the layer are tilted. Adsorption was
      also indicated by sum-frequency generation spectroscopy and XPS, the latter
      indicating that the most dominant amine-surface interaction was via electron
      donation from the nitrogen lone pair to the positively charged iron ions. Sum
      frequency generation spectroscopy was used to determine the alkyl chain
      conformation order and orientation on the surface. 

PMID- 24106788
TI  - Experimental and modeling study of the reaction C2F4 (+ M) <=> CF2 + CF2 (+ M).
AB  - The thermal dissociation reaction C2F4(+ M) -> 2CF2(+ M) was studied in shock
      waves monitoring CF2 radicals by their UV absorption. The absorption coefficients
      as functions of wavelength and temperature were redetermined and are represented
      in analytical form. Dissociation rate constants as functions of bath gas
      concentration [M] and temperature, from previous and the present work, are
      presented analytically employing falloff expressions from unimolecular rate
      theory. Equilibrium constants are determined between 1200 and 1500 K. The data
      are shown to be consistent, with a C-C bond energy of 67.5 (+/-0.5) kcal mol(-1).
      High-pressure limiting rate constants for dissociation and recombination are
      found to be unusually small. This phenomenon can be attributed to an unusually
      pronounced anisotropy of the potential energy surface, such as demonstrated by
      quantum-chemical calculations of the potential energy surface. 

PMID- 24106787
TI  - Multicentre randomized controlled trial of structured transition on diabetes care
      management compared to standard diabetes care in adolescents and young adults
      with type 1 diabetes (Transition Trial).
AB  - BACKGROUND: Transition from pediatric to adult diabetes care is a high risk
      period during which there is an increased rate of disengagement from care.
      Suboptimal transition has been associated with higher risks for acute and chronic
      diabetes-related complications. The period of emerging adulthood challenges
      current systems of healthcare delivery as many young adults with type 1 diabetes
      (T1D) default from diabetes care and are at risk for diabetes complications which
      are undetected and therefore untreated. Despite the importance of minimizing loss
      to follow-up there are no randomized control trials evaluating models of
      transition from pediatric to adult diabetes care. METHODS/DESIGN: This is a
      multicentre randomized controlled trial. A minimum of 188 subjects with T1D aged
      between 17 and 20 years will be evaluated. Eligible subjects will be recruited
      from three pediatric care centres and randomly assigned in a 1:1 ratio to a
      structured transition program that will span 18 months or to receive standard
      diabetes care. The structured transition program is a multidisciplinary, complex
      intervention aiming to provide additional support in the transition period. A
      Transition Coordinator will provide transition support and will provide the link
      between pediatric and adult diabetes care. The Transition Coordinator is central
      to the intervention to facilitate ongoing contact with the medical system as well
      as education and clinical support where appropriate. Subjects will be seen in the
      pediatric care setting for 6 months and will then be transferred to the adult
      care setting where they will be seen for one year. There will then be a one-year
      follow-up period for outcome assessment. The primary outcome is the proportion of
      subjects who fail to attend at least one outpatient adult diabetes specialist
      visit during the second year after transition to adult diabetes care. Secondary
      outcome measures include A1C frequency measurement and levels, diabetes related
      emergency room visits and hospital admissions, frequency of complication
      screening, and subject perception and satisfaction with care. DISCUSSION: This
      trial will determine if the support of a Transition Coordinator improves health
      outcomes for this at-risk population of young adults. TRIAL REGISTRATION:  TRIAL
      REGISTRATION NUMBER: NCT01351857.

PMID- 24106789
TI  - Functional characterisation of three members of the Vitis vinifera L. carotenoid
      cleavage dioxygenase gene family.
AB  - BACKGROUND: In plants, carotenoids serve as the precursors to C13-norisoprenoids,
      a group of apocarotenoid compounds with diverse biological functions. Enzymatic
      cleavage of carotenoids catalysed by members of the carotenoid cleavage
      dioxygenase (CCD) family has been shown to produce a number of industrially
      important volatile flavour and aroma apocarotenoids including beta-ionone,
      geranylacetone, pseudoionone, alpha-ionone and 3-hydroxy-beta-ionone in a range
      of plant species. Apocarotenoids contribute to the floral and fruity attributes
      of many wine cultivars and are thereby, at least partly, responsible for the
      "varietal character". Despite their importance in grapes and wine; carotenoid
      cleavage activity has only been described for VvCCD1 and the mechanism(s) and
      regulation of carotenoid catabolism remains largely unknown. RESULTS: Three
      grapevine-derived CCD-encoding genes have been isolated and shown to be
      functional with unique substrate cleavage capacities. Our results demonstrate
      that the VvCCD4a and VvCCD4b catalyse the cleavage of both linear and cyclic
      carotenoid substrates. The expression of VvCCD1, VvCCD4a and VvCCD4b was detected
      in leaf, flower and throughout berry development. VvCCD1 expression was
      constitutive, whereas VvCCD4a expression was predominant in leaves and VvCCD4b in
      berries. A transgenic population with a 12-fold range of VvCCD1 expression
      exhibited a lack of correlation between VvCCD1 expression and carotenoid
      substrates and/or apocarotenoid products in leaves, providing proof that the in
      planta function(s) of VvCCD1 in photosynthetically active tissue is distinct from
      the in vitro activities demonstrated. The isolation and functional
      characterisation of VvCCD4a and VvCCD4b identify two additional CCDs that are
      functional in grapevine. CONCLUSIONS: Taken together, our results indicate that
      the three CCDs are under various levels of control that include gene expression
      (spatial and temporal), substrate specificity and compartmentalisation that act
      individually and/or co-ordinately to maintain carotenoid and volatile
      apocarotenoid levels in plants. Altering the expression of VvCCD1 in a transgenic
      grapevine population illustrated the divergence between the in vitro enzyme
      activity and the in planta activity of this enzyme, thereby contributing to the
      efforts to understand how enzymatic degradation of carotenoids involved in
      photosynthesis occurs. The identification and functional characterisation of
      VvCCD4a and VvCCD4b suggest that these enzymes are primarily responsible for
      catalysing the cleavage of plastidial carotenoids.

PMID- 24106791
TI  - Cases of difficult suture removal following the McDonald procedure.
AB  - We examined the clinical significance of difficult suture removal following the
      McDonald procedure. We examined 117 patients following the McDonald procedure
      with a singleton pregnancy who delivered at >=34 weeks of gestation. Difficult
      suture removal was defined as when spinal anesthesia was required for suture
      removal. Seven patients (6.0%) were defined as involving difficult suture
      removal. The cervical length in the difficult-removal-group was significantly
      shorter than that in the easy-removal-group at suture removal (p = 0.04). If the
      cervical length was shorter than 20 mm, the odds ratio for difficult suture
      removal was 9.0 (95% CI 1.6-49, p = 0.01). The progression of cervical ripening
      following the McDonald suture may be associated with an increased risk of
      difficult suture removal.

PMID- 24106792
TI  - A survey of surgical team members' perceptions of near misses and attitudes
      towards Time Out protocols.
AB  - BACKGROUND: Medical errors are inherently of concern in modern health care.
      Although surgical errors as incorrect surgery (e.g., wrong patient, wrong site,
      or wrong procedure) are infrequent, they are devastating events to experience. To
      gain insight about incidents that could lead to incorrect surgery, we surveyed
      how surgical team members perceive near misses and their attitudes towards the
      use of Time Out protocols in the operating room. We hypothesised that perceptions
      of near-miss experiences and attitudes towards Time Out protocols vary widely
      among surgical team members. METHODS: This cross-sectional study (N = 427)
      included surgeons, anaesthetists, nurse anaesthetists, and operating room nurses.
      The questionnaire consisted of 14 items, 11 of which had dichotomous responses (0
      = no; 1 = yes) and 3 of which had responses on an ordinal scale (never = 0;
      sometimes = 1; often = 2; always = 3). Items reflected team members' experience
      of near misses or mistakes; their strategies for verifying the correct patient,
      site, and procedure; questions about whether they believed that these mistakes
      could be avoided using the Time Out protocol; and how they would accept the
      implementation of the protocol in the operating room. RESULTS: In the operating
      room, 38% of respondents had experienced uncertainty of patient identity, 81% had
      experienced uncertainty of the surgical site or side, and 60% had prepared for
      the wrong procedure. Sixty-three per cent agreed that verifying the correct
      patient, site, and procedure should be a team responsibility. Thus, only nurse
      anaesthetists routinely performed identity checks prior to surgery (P <= 0.001).
      Of the surgical team members, 91% supported implementation of a Time Out protocol
      in their operating rooms. CONCLUSION: The majority of our surgical personnel
      experienced near misses with regard to correct patient identity, surgical site,
      or procedure. Routines for ensuring the correct patient, site, and surgical
      procedure must involve all surgical team members. We find that the near-miss
      experiences are a wake-up call for systematic risk reducing efforts and the use
      of checklists in surgery.

PMID- 24106794
TI  - Characterization of PVL-positive MRSA from Norway.
AB  - Norway is a country in which the Methicillin-resistant Staphylococcus aureus
      (MRSA) prevalence has been low for the last decades. There are virtually no
      epidemic, hospital-acquired MRSA because of an emphasis on strict infection
      control rules and restrictive use of antibiotics. However, community-acquired
      and/or Panton-Valentine leucocidin (PVL)-positive MRSA need to be monitored as
      these strains are transmitted outside of healthcare facilities and cannot be
      contained by healthcare-centred strategies. All 179 non-repetitive isolates of
      PVL-positive MRSA that were received during 2011 at the regional infection
      control laboratory at Akershus University Hospital were preserved and spa typed.
      Seventy isolates were further characterized by DNA microarray hybridization. The
      most common PVL-MRSA lineages were ST8-MRSA-IV and CC30-MRSA-IV. Further common
      clones were CC80-MRSA-IV and CC5-MRSA-IV. Other clones were found sporadically.
      These included ST772-MRSA-V and ST834-MRSA-IV, the latter in patients with
      epidemiological connections to the Philippines. Small-scale family outbreaks
      affecting at least 49 individuals were noted, with numbers of known cases per
      outbreak ranging from two to seven. At least 24 cases were related to foreign
      travel to Eritrea, India, Iraq, Macedonia, Pakistan, the Philippines, Poland,
      Singapore, Turkey, the USA and Vietnam. These data show that community
      acquired/PVL-positive MRSA are not yet a major public health problem in Southern
      Norway. Our study corroborates the current practice of mandatory screening of
      patients and staff with travel histories, admissions or employment in healthcare
      institutions outside the Scandinavian countries or with known MRSA contacts.

PMID- 24106795
TI  - Construction of a shuttle expression vector with a promoter functioning in both
      halophilic Archaea and Bacteria.
AB  - A shuttle expression vector, designated as pAJ, was constructed based on the
      Haloferax volcanii-Escherichia coli shuttle vector pSY1. This new construct
      contains the amyH promoter from Haloarcula hispanica and was able to confer the
      promoter activity in both Hfx. volcanii and E. coli. pAJ successfully expressed
      proteins in Hfx. volcanii or E. coli, rendering it feasible to express target
      proteins in corresponding domains. In addition, pAJ contains a multiple cloning
      site with 11 restriction sites and a 6*His tag sequence, and the vector size was
      decreased to 8903 bp. To the best of our knowledge, pAJ is the first reported
      shuttle expression vector that can express proteins in both Bacteria and Archaea.
      Importantly, pAJ can even express the haloarchaeal heat shock protein DnaK in
      both domains. In conclusion, this novel vector only provides researchers with a
      new means to manipulate genes or express proteins in Haloarchaea but also serves
      as a convenient tool for the comparative study of the function of some highly
      conserved genes in Haloarchaea and in Bacteria. 

PMID- 24106796
TI  - Analgesic effects of microwave ablation of bone and soft tissue tumors under
      local anesthesia.
AB  - OBJECTIVE: To assess the feasibility and efficacy of microwave ablation (MWA) of
      painful refractory bone and soft tissue tumors performed under local anesthesia.
      STUDY DESIGN: A retrospective study between 2011 and 2013. SETTING: A single
      center, Academic Interventional Pain Management Unit. SUBJECTS: Fifteen patients
      with 25 refractory painful bone (N = 19) or soft tissue (N = 6) tumors treated
      with MWA were consecutively included. METHOD: Local Institutional Review Board
      approval was obtained, and written informed consent was waived. Lesions included
      spinal (N = 3), sacral (N = 4), and extraspinal (N = 18) locations. Pain was
      measured on a visual analog scale (VAS) from 0 to 10 before and immediately after
      procedure, at 1 week, and on a monthly basis following procedure. MWA procedures
      were always performed under computed tomography guidance and local anesthesia
      along with nitrous oxide inhalation. RESULTS: Mean ablation time was 4.09 minutes
      (range 1-11) with an average of 4.2 cycles with a mean ablation power of 60 W.
      Preprocedure mean VAS score was 7.2 +/- 0.97 (range 6-9). Follow-up postprocedure
      VAS scores were as follows: day 0: 1.64 +/- 1.86, day 7: 1.82 +/- 1.79, month 1:
      2.05 +/- 2.03 (14/15 patients), month 3: 2.13 +/- 1.81, month 6: 2.36 +/- 2.17;
      and were statistically significant (P < 0.001). Mean pain relief was 5.5 months.
      CONCLUSION: MWA is feasible, safe, and effective in the management of painful
      refractory bone and soft tissue tumors. It may therefore be considered as a
      potential alternative to existing percutaneous ablation techniques in the
      management of bone and soft tissue tumors.

PMID- 24106797
TI  - Facile synthesis of palladium right bipyramids and their use as seeds for
      overgrowth and as catalysts for formic acid oxidation.
AB  - Controlling the shape and thus facets of metal nanocrystals is an effective way
      to enhance their performance in catalytic reactions. While Pd nanocrystals with a
      myriad of shapes have been successfully prepared with good uniformity and in high
      yield, Pd right bipyramids (RBPs) that have a singly twinned structure have been
      elusive. We report a facile route based on polyol reduction for the synthesis of
      Pd RBPs with purity >90% and sizes controlled in the range 5-15 nm. The success
      of our synthesis relies on the use of iodide ions to manipulate the strength of
      an oxidative etchant and selectively cap the Pd{100} facets. The as-prepared RBPs
      could serve as seeds to generate a set of Pd nanocrystals with novel shapes and
      structures. The RBPs also exhibited enhanced catalytic activity toward formic
      acid oxidation, with a current density 2.5 and 7.1 times higher than those of the
      single-crystal Pd nanocubes (which were also mainly covered by {100} facets) and
      commercial Pd black, respectively. 

PMID- 24106799
TI  - Conductometric monitoring of protein-protein interactions.
AB  - Conductometric monitoring of protein-protein and protein-sterol interactions is
      here proved feasible by coupling quartz crystal microbalance with dissipation
      monitoring (QCM_D) to nucleic acid programmable protein arrays (NAPPA). The
      conductance curves measured in NAPPA microarrays printed on quartz surface
      allowed the identification of binding events between the immobilized proteins and
      the query. NAPPA allows the immobilization on the quartz surface of a wide range
      of proteins and can be easily adapted to generate innumerous types of biosensors.
      Indeed multiple proteins on the same quartz crystal have been tested and
      envisaged proving the possibility of analyzing the same array for several
      distinct interactions. Two examples of NAPPA-based conductometer applications
      with clinical relevance are presented herein, the interaction between the
      transcription factors Jun and ATF2 and the interaction between Cytochrome P540scc
      and cholesterol. 

PMID- 24106800
TI  - Temperature induced structural transformations and gas adsorption in the zeolitic
      imidazolate framework ZIF-8: a Raman study.
AB  - Here we have used Raman spectroscopy to investigate molecular level changes in
      the zeolitic imidazolate framework ZIF-8 (a prototypical zeolite-like porous
      metal organic framework) as a function of temperature. Temperature dependent
      Raman spectra suggest that at low temperature the softening of the C-H stretching
      frequencies is due to the decrease in steric hindrance between the methyl groups
      of methyl imidazole. The larger separation between the methyl groups opens the
      window for increased nitrogen and methane uptake at temperatures below 153 K. The
      appearance of Raman bands at 2323 cm(-1) and 2904 cm(-1) at or below 153 K in ZIF
      8 are characteristic signatures of the adsorbed nitrogen and methane gases
      respectively. Nanoscale ZIF-8 uptakes more molecules than bulk ZIF-8, and as a
      result we could provide evidence for encaged CO2 at 203 K yielding its Raman mode
      at 1379 cm(-1). 

PMID- 24106802
TI  - On the identification of conflicting contiguities in ancestral genome
      reconstruction.
AB  - In computional biology, up-to-date homology-based methods for the reconstruction
      of ancestral gene orders usually rely on two phases. First, potential ancestral
      co-localizations of some genomic markers are detected from homologies between
      extant species. Next, the assembling phase mainly consists in resolving the
      conflicts between the potential ancestral features. This can be done using many
      methods, but one of the most advanced solutions is to identify and discard from
      the set of potential features those that belong to inclusivewise minimal
      conflicting sets of features. It relies on the consecutive ones property (C1P),
      and the notion of minimal conflicting set (MCS), widely used in physical mapping
      problems. Let C be a finite set of n elements and R= {r(1), r(2), . . . , r(m)} a
      family of m subsets of C. A subset X of R satisfies the C1P if there exists a
      permutation P of C such that each r(i) in X is an interval of P. An MCS S ? R is
      a subset of R that does not satisfy the C1P, but such that any of its proper
      subsets does. In this article, we present a new simpler and faster algorithm to
      decide if a given element r ? R belongs to at least one MCS. Our algorithm runs
      in O(n(2)m(2) + nm(7)), largely improving upon the current O(m(6)n(5)(m + n)(2)
      log(m + n)) fastest algorithm. The new algorithm is based on an alternative
      approach considering minimal forbidden induced subgraphs of interval graphs
      instead of Tucker matrices.

PMID- 24106801
TI  - Cystic fibrosis transmembrane conductance regulator activation by roflumilast
      contributes to therapeutic benefit in chronic bronchitis.
AB  - Cigarette smoking causes acquired cystic fibrosis transmembrane conductance
      regulator (CFTR) dysfunction and is associated with delayed mucociliary clearance
      and chronic bronchitis. Roflumilast is a clinically approved phosphodiesterase 4
      inhibitor that improves lung function in patients with chronic bronchitis. We
      hypothesized that its therapeutic benefit was related in part to activation of
      CFTR. Primary human bronchial epithelial (HBE) cells, Calu-3, and T84 monolayers
      were exposed to whole cigarette smoke (WCS) or air with or without roflumilast
      treatment. CFTR-dependent ion transport was measured in modified Ussing chambers.
      Airway surface liquid (ASL) was determined by confocal microscopy. Intestinal
      fluid secretion of ligated murine intestine was monitored ex vivo. Roflumilast
      activated CFTR-dependent anion transport in normal HBE cells with a half maximal
      effective concentration of 2.9 nM. Roflumilast partially restored CFTR activity
      in WCS-exposed HBE cells (5.3 +/- 1.1 MUA/cm(2) vs. 1.2 +/- 0.2 MUA/cm(2)
      [control]; P < 0.05) and was additive with ivacaftor, a specific CFTR potentiator
      approved for the treatment of CF. Roflumilast improved the depleted ASL depth of
      HBE monolayers exposed to WCS (9.0 +/- 3.1 MUm vs. 5.6 +/- 2.0 MUm [control]; P <
      0.05), achieving 79% of that observed in air controls. CFTR activation by
      roflumilast also induced CFTR-dependent fluid secretion in murine intestine,
      increasing the wet:dry ratio and the diameter of ligated murine segments.
      Roflumilast activates CFTR-mediated anion transport in airway and intestinal
      epithelia via a cyclic adenosine monophosphate-dependent pathway and partially
      reverses the deleterious effects of WCS, resulting in augmented ASL depth.
      Roflumilast may benefit patients with chronic obstructive pulmonary disease with
      chronic bronchitis by activating CFTR, which may also underlie noninfectious
      diarrhea caused by roflumilast. 

PMID- 24106803
TI  - Participation in patient support groups among cancer survivors: do psychosocial
      and medical factors have an impact?
AB  - A better understanding of the role of psychosocial resources and factors
      associated with participating in patient support groups appears to be important
      for the development and implementation of cancer survivorship care plans. We
      therefore investigated the frequency of participation in and satisfaction with
      patient support groups after completion of a rehabilitation programme and aimed
      to examine differences in demographic, medical and psychosocial characteristics
      between group participants and non-participants. We further aimed to identify
      predictors of participation in patient support groups. A total of 1281 eligible
      patients (75.5% participation rate) were recruited on average 11 months post
      diagnosis and assessed at the beginning (t1 ), at the end (t2 ) and 12 months
      after rehabilitation (t3 ). Study participants completed self-report measures
      assessing support-group participation and satisfaction, psychosocial distress
      (anxiety, fear of cancer recurrence, depression), social support, coping, quality
      of life, pain and treatment-related characteristics. Sixty-seven patients (7.6%)
      participated in a patient self-help group. Being unemployed, undergoing an
      increased number of overall treatments, and a higher active emotion-oriented
      coping style significantly predicted self-help group participation; the
      predictive power of the multivariate logistic regression model was rather weak
      (Nagelkerke's R(2) = 0.07). Our data provide evidence that self-help group
      participation in cancer patients may be largely related to other factors than
      medical or psychosocial distress. 

PMID- 24106805
TI  - Structural effects of pH and deacylation on surfactant protein C in an organic
      solvent mixture: a constant-pH MD study.
AB  - The pulmonary surfactant protein C (SP-C) is a small highly hydrophobic protein
      that adopts a mainly helical structure while associated with the membrane but
      misfolds into a beta-rich metastable structure upon deacylation, membrane
      dissociation, and exposure to the neutral pH of the aqueous alveolar subphase,
      eventually leading to the formation of amyloid aggregates associated with
      pulmonary alveolar proteinosis. The present constant-pH MD study of the acylated
      and deacylated isoforms of SP-C in a chloroform/methanol/water mixture, often
      used to mimic the membrane environment, shows that the loss of the acyl groups
      has a structural destabilizing effect and that the increase of pH promotes
      intraprotein contacts which contribute to the loss of helical structure in
      solution. These contacts result from the poor solvation of charged groups by the
      solvent mixture, which exhibits a limited membrane-mimetic character. Although a
      single SP-C molecule was used in the simulations, we propose that analogous
      intermolecular interactions may play a role in the early stages of the protein
      misfolding and aggregation in this mixture. 

PMID- 24106804
TI  - Self-Reported quality of life in adults with attention-deficit/hyperactivity
      disorder and executive function impairment treated with lisdexamfetamine
      dimesylate: a randomized, double-blind, multicenter, placebo-controlled, parallel
      group study.
AB  - BACKGROUND: This study examined the effects of lisdexamfetamine dimesylate (LDX)
      on quality of life (QOL) in adults with attention-deficit/hyperactivity disorder
      (ADHD) and clinically significant executive function deficits (EFD). METHODS:
      This report highlights QOL findings from a 10-week randomized placebo-controlled
      trial of LDX (30-70 mg/d) in adults (18-55 years) with ADHD and EFD (Behavior
      Rating Inventory of EF-Adult, Global Executive Composite [BRIEF-A GEC] >=65). The
      primary efficacy measure was the self-reported BRIEF-A; a key secondary measure
      was self-reported QOL on the Adult ADHD Impact Module (AIM-A). The clinician
      completed ADHD Rating Scale version IV (ADHD-RS-IV) with adult prompts and
      Clinical Global Impressions-Severity (CGI-S) were also employed. The Adult ADHD
      QoL (AAQoL) was added while the study was in progress. A post hoc analysis
      examined the subgroup having evaluable results from both AIM-A and AAQoL.
      RESULTS: Of 161 randomized (placebo, 81; LDX, 80), 159 were included in the
      safety population. LDX improved AIM-A multi-item domain scores versus placebo; LS
      mean difference for Performance and Daily Functioning was 21.6 (ES, 0.93,
      P<.0001); Impact of Symptoms: Daily Interference was 14.9 (ES, 0.62, P<.0001);
      Impact of Symptoms: Bother/Concern was 13.5 (ES, 0.57, P=.0003);
      Relationships/Communication was 7.8 (ES, 0.31, P=.0302); Living With ADHD was 9.1
      (ES, 0.79, P<.0001); and General Well-Being was 10.8 (ES, 0.70, P<.0001). AAQoL
      LS mean difference for total score was 21.0; for subscale: Life Productivity was
      21.0; Psychological Health was 12.1; Life Outlook was 12.5; and Relationships was
      7.3. In a post hoc analysis of participants with both AIM-A and AAQoL scores, AIM
      A multi-item subgroup analysis scores numerically improved with LDX, with smaller
      difference for Impact of Symptoms: Daily Interference. The safety profile of LDX
      was consistent with amphetamine use in previous studies. CONCLUSIONS: Overall,
      adults with ADHD/EFD exhibited self-reported improvement on QOL, using the AIM-A
      and AAQoL scales in line with medium/large ES; these improvements were paralleled
      by improvements in EF and ADHD symptoms. The safety profile of LDX was similar to
      previous studies. TRIAL REGISTRATION: ClinicalTrials.gov, NCT01101022.

PMID- 24106806
TI  - Target-controlled infusion of propofol versus intermittent bolus of a sedative
      cocktail regimen in deep sedation for gastrointestinal endoscopy: comparison of
      cardiovascular and respiratory parameters.
AB  - OBJECTIVE: To investigate whether target-controlled infusion (TCI) with propofol,
      a method that has theoretically better control of drug concentration, produces
      less cardiovascular and respiratory suppression than an intermittent bolus of a
      sedative cocktail regimen in deep sedation for gastrointestinal endoscopy.
      METHODS: In total 100 participants who had undergone esophagoduodenoscopy (EGD)
      and 120 who had undergone colonoscopy were prospectively and randomly enrolled to
      receive TCI with propofol or intermittent bolus of cocktail regimen containing
      midazolam, alfentanil and propofol until they were unresponsive to verbal
      commands. The target concentration was adjusted and the bolus of the cocktail
      regimen was added based on their responses. The nadir values of heart rate, blood
      pressure and oxygen saturation during and after the procedure were recorded.
      RESULTS: The nadir systolic blood pressure during the endoscopy in the cocktail
      regimen group was significantly lower than that in the TCI with propofol group.
      In the cocktail regimen group, the incidence of hypotension during colonoscopy
      and that of bradycardia during EGD were higher than those in the TCI with
      propofol group. No participants in the TCI with propofol group experienced
      hypoxia during endoscopy. In the cocktail regimen group, six participants who had
      undergone EGD and six who had undergone colonoscopy showed transient hypoxic
      episodes during or after endoscopy. CONCLUSION: TCI with propofol produced less
      cardiovascular and respiratory suppression than intermittent bolus of a sedative
      cocktail regimen in deep sedation for gastrointestinal endoscopy.

PMID- 24106807
TI  - Using NMR chemical shift imaging to monitor swelling and molecular transport in
      drug-loaded tablets of hydrophobically modified poly(acrylic acid): methodology
      and effects of polymer (in)solubility.
AB  - A new technique has been developed using NMR chemical shift imaging (CSI) to
      monitor water penetration and molecular transport in initially dry polymer
      tablets that also contain small low-molecular weight compounds to be released
      from the tablets. Concentration profiles of components contained in the swelling
      tablets could be extracted via the intensities and chemical shift changes of
      peaks corresponding to protons of the components. The studied tablets contained
      hydrophobically modified poly(acrylic acid) (HMPAA) as the polymer component and
      griseofulvin and ethanol as hydrophobic and hydrophilic, respectively, low
      molecular weight model compounds. The water solubility of HMPAA could be altered
      by titration with NaOH. In the pure acid form, HMPAA tablets only underwent a
      finite swelling until the maximum water content of the polymer-rich phase, as
      confirmed by independent phase studies, had been reached. By contrast, after
      partial neutralization with NaOH, the polyacid became fully miscible with water.
      The solubility of the polymer affected the water penetration, the polymer
      release, and the releases of both ethanol and griseofulvin. The detailed NMR CSI
      concentration profiles obtained highlighted the clear differences in the
      disintegration/dissolution/release behavior for the two types of tablet and
      provided insights into their molecular origin. The study illustrates the
      potential of the NMR CSI technique to give information of importance for the
      development of pharmaceutical tablets and, more broadly, for the general
      understanding of any operation that involves the immersion and ultimate
      disintegration of a dry polymer matrix in a solvent. 

PMID- 24106808
TI  - Assessment of pregnancy-associated, within-woman change in uterine length.
AB  - OBJECTIVE: To evaluate how absolute uterine length changes as a result of
      pregnancy. METHODS: Longitudinal repeated-measures study of all women presenting
      to a university-affiliated clinic for uterine sounding prior to in vitro
      fertilization (IVF) who went on to deliver at term and return for repeat
      measurement from 2002 to 2012. Change in uterine length was assessed by the
      Wilcoxon signed-rank test. RESULTS: Among 495 women, mean pregnancy-associated
      change in uterine length was 0.0 cm (SD +/- 0.7, p = 0.84), with 31% of women
      experiencing no change and 75% of women experiencing a change <=0.5 cm. Mean
      uterine lengths at pre-cycle and repeat measurement were 7.2 cm (SD +/- 0.7) and
      7.2 cm (SD +/- 0.7) with medians of 7.0 cm (IQR 7.0-7.5) and 7.0 cm (IQR 6.8
      7.8), respectively. Change in uterine length did not vary by gestational number
      or within time interval between measurements (all p > 0.5). CONCLUSIONS: There
      was no difference in uterine length before and after term pregnancy. The finding
      of minimal variation in uterine length both across and within women suggests
      uterine length may be relatively stable such that patients undergoing IVF after
      term IVF pregnancy may not require repeat measurement. Future studies might
      assess pregnancy-associated sonographic changes in uterine volume and the
      relationship between uterine length and IVF outcomes.

PMID- 24106809
TI  - Photodegradable supramolecular hydrogels with fluorescence turn-on reporter for
      photomodulation of cellular microenvironments.
AB  - Photodegradable hydrogels that allow 3D encapsulation of cells are important
      biomaterials to modulate cellular microenvironments with temporal and spatial
      resolution. Herein we report a photodegradable hydrogel formed by the self
      assembly of short peptides modified with a novel phototrigger. The phototrigger
      is a biaryl-substituted tetrazole moiety that, upon mild light irradiation,
      undergoes rapid intramolecular photoclick ligation to form a highly fluorescent
      pyrazoline moiety. Short peptides linked with a tetrazole-containing moiety,
      Tet(I) or Tet(II), are able to self-assemble into hydrogels, among which the
      Tet(I)-GFF and Tet(II)-GFRGD gels show good mechanical strength and
      biocompatibility for 3D encapsulation and prolonged culture of live cells. The
      phototriggered tetrazole-to-pyrazoline transformation generates a highly
      fluorescent reporter and induces the disassembly of the hydrogel matrix by
      disturbing the balance between hydrophilic interaction and pi-pi stacking of the
      self-assembled system. Photomodulation of cellular microenvironments was
      demonstrated not only for the cells grown on top of the gel but also for stem
      cells encapsulated inside the hydrogels. 

PMID- 24106810
TI  - Characterization of norovirus RNA replicase for in vitro amplification of RNA.
AB  - BACKGROUND: The isothermal amplification of RNA in vitro has been used for the
      study of in vitro evolution of RNA. Although Qbeta replicase has been
      traditionally used as an enzyme for this purpose, we planned to use norovirus
      replicase (NV3D(pol)) due to its structural simplicity in the scope of in vitro
      autonomous evolution of the protein. Characteristics of the enzyme NV3D(pol) in
      vitro were re-evaluated in this context. RESULTS: NV3D(pol), synthesized by using
      a cell-free translation system, represented the activities which were reported in
      the previous several studies and the reports were not fully consistent each
      other. The efficiency of the initiation of replication was dependent on the 3'
      terminal structure of single-stranded RNA template, and especially, NV3D(pol)
      preferred a self-priming small stem-loop. In the non-self-priming and primer
      independent replication reaction, the presence of -CCC residues at the 3'
      terminus increased the initiation efficiency and we demonstrated the one-pot
      isothermal RNA (even dsRNA) amplification by 16-fold. NV3D(pol) also showed a
      weak activity of elongation-reaction from a long primer. Based on these results,
      we present a scheme of the primer-independent isothermal amplification of RNA
      with NV3D(pol) in vitro. CONCLUSIONS: NV3D(pol) can be used as an RNA replicase
      in in vitro RNA + protein evolution with the RNA of special terminal sequences.

PMID- 24106813
TI  - Invasive Mycobacterium chelonae infection.

PMID- 24106814
TI  - Construction of polyfunctional coatings assisted by gallic acid to facilitate co
      immobilization of diverse biomolecules.
AB  - Designing a multifunctional surface based on the coimmobilization of two or more
      diverse biomolecules with synergic action is very important in certain cases. In
      this work, a facile method by two-step aimed to construct a polyfunctional
      coating containing -COOH, -NH2, and phenol/quinine groups was reported. The first
      step was to introduce amine groups onto target modified-surface by coating with
      plasma polymerized allylamine (PPAam), followed by the second-step conjugation of
      gallic acid (3,4,5-trihydroxybenzoic acid) onto the PPAam surface. The density of
      -COOH, -NH2, and phenol/quinone groups could be regulated easily by adjusting the
      reaction time of GA conjugation, making it possible to coimmobilize two or three
      diverse molecules. This has been shown by the successful coimmobilization of anti
      CD34 antibody and vascular endothelial growth factor (VEGF). The surface
      coimmobilized with the anti-CD34 antibody and VEGF presented significant
      enhancement in the capture of endothelial progenitor cells (EPCs) and the growth
      of human umbilical vein endothelial cells (HUVECs). These data suggest the huge
      potential of such polyfunctional coating for tailoring the desired interfacial
      properties of materials through selectively conjugating two or more diverse
      bioactive molecules with synergic action. 

PMID- 24106815
TI  - Bilateral transversus abdominis plane (TAP) block with 24 hours ropivacaine
      infusion via TAP catheters: A randomized trial in healthy volunteers.
AB  - BACKGROUND: The analgesic effect of a TAP block has been investigated in various
      surgical settings. There are however limited information about block level and
      block duration. Furthermore, there is a lack of information about continuous TAP
      block after ultrasound-guided posterior TAP blocks.The aim of this double-blind
      randomized study was therefore to investigate the effect of an ultrasound-guided
      posterior TAP block with 24 hours local anesthetic infusion via a TAP catheter.
      METHODS: In this randomized study 8 male volunteers received a bilateral TAP
      block (20 mLs 0.5% ropivacaine) and were allocated to receive active infusion
      (ropivacaine 0.2% 5 mL/hr) via a TAP catheter on one side and placebo infusion on
      the other side. PRIMARY OUTCOME: Dermatomal sensory block involvement after 24
      hours evaluated with pinprick. SECONDARY OUTCOMES: Sensory block involvement
      evaluated with cold test and heat-pain detection thresholds (HPDT) on the
      abdominal wall. Assessment points: 15 min before block performance and 1, 4, 8,
      12 and 24 hours after block performance. RESULTS: The TAP block primarily
      involved sensory changes in the Th10 to Th12 dermatomes. On the placebo side
      there was a decrease in extension beginning at 4-8 hours after block performance
      and with no detectable effect beyond 12 hours. Median number of dermatomes
      anesthetized (pinprick) at 24 hours after block performance was 1.5 (0-3) on the
      active side compared with 0 (0-0) on the placebo side (P = 0.039).There were no
      statistical significant between-side differences in HPDT measurements at 24 hours
      after block performance. CONCLUSIONS: The spread of sensory block following
      ultrasound-guided posterior TAP block is partly maintained by a continuous 24
      hour ropivacaine infusion through a TAP catheter. TRIAL REGISTRATION: The study
      was registered at NCT01577940.

PMID- 24106816
TI  - Isolation of oxalotrophic bacteria able to disperse on fungal mycelium.
AB  - A technique based on an inverted Petri dish system was developed for the growth
      and isolation of soil oxalotrophic bacteria able to disperse on fungal mycelia.
      The method is related to the 'fungal highways' dispersion theory in which
      mycelial fungal networks allow active movement of bacteria in soil.
      Quantification of this phenomenon showed that bacterial dispersal occurs
      preferentially in upper soil horizons. Eight bacteria and one fungal strain were
      isolated by this method. The oxalotrophic activity of the isolated bacteria was
      confirmed through calcium oxalate dissolution in solid selective medium. After
      separation of the bacteria-fungus couple, partial sequencing of the 16S and the
      ITS1 and ITS2 sequences of the ribosomal RNA genes were used for the
      identification of bacteria and the associated fungus. The isolated oxalotrophic
      bacteria included strains related to Stenotrophomonas, Achromobacter, Lysobacter,
      Pseudomonas, Agrobacterium, Cohnella, and Variovorax. The recovered fungus
      corresponded to Trichoderma sp. A test carried out to verify bacterial transport
      in an unsaturated medium showed that all the isolated bacteria were able to
      migrate on Trichoderma hyphae or glass fibers to re-colonize an oxalate-rich
      medium. The results highlight the importance of fungus-driven bacterial dispersal
      to understand the functional role of oxalotrophic bacteria and fungi in soils. 

PMID- 24106818
TI  - In-home HIV testing and nevirapine dosing by traditional birth attendants in
      rural Zambia: a feasibility study.
AB  - INTRODUCTION: Access to lifesaving prevention of mother-to-child transmission
      (PMTCT) services is problematic in rural Zambia. The simplest intervention used
      in Zambia has been 2-dose nevirapine (NVP) administration in the peripartum
      period, a regimen of 1 NVP tablet to the mother at the onset of labor and 1 dose
      in the form of syrup to the newborn within 4 to 72 hours after birth. This 2-dose
      regimen has been shown to reduce MTCT by nearly 50%. We set out to demonstrate
      that in-home HIV testing and NVP dosing by traditional birth attendants (TBAs) is
      feasible and acceptable by women in rural Zambia. METHODS: This was a pilot
      program using TBAs to perform rapid saliva-based HIV testing and administer
      single-dose NVP in tablet form to the mother at the onset of labor and syrup to
      the infant after birth. RESULTS: A total of 280 pregnant women were consented and
      enrolled into the program, of whom 124 (44.3%) gave birth at home with the
      assistance of a trained TBA. Of those, 16 (12.9%) were known to be HIV positive,
      and 101 of the remaining 108 (93.5%) accepted a rapid HIV test. All these women
      tested HIV negative. In the subset of 16 mothers who were HIV positive, 13
      (81.3%) took single-dose NVP administered by a TBA between 1 and 24 hours prior
      to birth and 100% of exposed newborns (16 of 16) received NVP syrup within 72
      hours after birth, 80% of whom were dosed in the first 24 hours of life.
      DISCUSSION: With the substantial shortage of human resources in public health
      care throughout sub-Saharan Africa, it is extremely valuable to utilize lay
      health care workers to help extended services beyond the level of the facility.
      Given the high uptake of PMTCT services we believe that TBAs with proper training
      and support can successfully provide country-approved PMTCT.

PMID- 24106819
TI  - Evaluation of a PCR method to determine the clinical significance of blood
      cultures with Staphylococcus epidermidis in patients with hematological
      malignancies.
AB  - The aim was to investigate whether the detection and quantification of
      Staphylococcus epidermidis DNA in blood could distinguish S. epidermidis blood
      stream infections (BSIs) from blood culture contaminations in patients with
      hematological malignancies. The hld gene was chosen to identify S. epidermidis
      DNA and DNA in blood samples was detected by real-time PCR. Blood samples were
      obtained simultaneously with blood cultures positive for S. epidermidis (n = 30),
      during blood culture-negative episodes (n = 10) and episodes of bacteremia with
      other bacteria than S. epidermidis (n = 4) and from healthy blood donors (n =
      10). In addition, DNA from S. epidermidis and a selection of other bacterial
      species were analyzed. Three different sets of criteria were used to classify
      episodes with positive blood cultures with S. epidermidis as BSIs or
      contaminations. All DNA preparations from S. epidermidis (n = 48) were hld
      positive, but other bacterial species (n = 13) were negative. Sixteen (53%) of 30
      blood samples from patients with blood cultures positive for S. epidermidis were
      hld-positive, but none of the controls. There was no clear association between a
      positive hld PCR and episodes interpreted as BSIs. In conclusion, hld PCR failed
      to distinguish S. epidermidis BSIs from blood culture contaminations in patients
      with hematological malignancies.

PMID- 24106820
TI  - AA amyloidosis in a polyarteritis nodosa patient treated with tocilizumab.
AB  - Amyloid A (AA) (secondary) amyloidosis represents a severe complication of
      chronic inflammatory diseases. Since pathogenic mechanisms point to the central
      role of interleukin 6 (IL-6) in the process of amyloid AA generation, IL-6
      blockade seems an attractive therapeutic option. We report a case of a patient
      with polyarteritis nodosa complicated by AA amyloidosis treated with tocilizumab.

PMID- 24106821
TI  - Prevalence, characteristics, and management of childhood functional abdominal
      pain in general practice.
AB  - OBJECTIVE: To (i) describe the proportion of children presenting with abdominal
      pain diagnosed by the GP as functional abdominal pain (GPFAP); (ii) evaluate the
      association between patient and disease characteristics and GPFAP; (iii) describe
      diagnostic management by the GP in children presenting with abdominal pain, and
      (iv) evaluate whether children with GPFAP fulfill diagnostic criteria for
      functional abdominal pain (FAP) as described in current literature: chronic
      abdominal pain (CAP) and the Rome III criteria (PRC-III) for abdominal pain
      related functional gastrointestinal disorders (FGID). DESIGN: Cross-sectional
      study. SETTING: General practices in the Netherlands. SUBJECTS: 305 children aged
      4-17 years consulting for abdominal pain. MAIN OUTCOME MEASURES: GPFAP, CAP,
      FGIDs. RESULTS: 89.2% of children were diagnosed with GPFAP. Headaches and
      bloating were positively associated with GPFAP whereas fever and > 3 red flag
      symptoms were inversely associated. Additional diagnostic tests were performed in
      26.8% of children. Less than 50% of all children with GPFAP fulfilled criteria
      for CAP and FGIDs; in 47.9% of patients the duration of symptoms at presentation
      was less than three months. CONCLUSIONS: In almost 90% of children included in
      this study the GP suspected no organic cause for the abdominal pain. GPs diagnose
      FAP in children without alarm symptoms and order diagnostic testing in one out of
      four children presenting with abdominal pain. No difference was found in GPs'
      management between children with a diagnosis of GPFAP and other diagnoses. Only
      about half of the children with a GP diagnosis of FAP fulfilled time-criteria of
      FAP as defined in the literature.

PMID- 24106822
TI  - Fat emulsion given to very low-birthweight infants increases urinary L-FABP.
AB  - BACKGROUND: In premature infants, many factors influence the function of renal
      tubules, such as asphyxia, respiratory disorders, use of high-concentration
      oxygen, hypotension, and drug treatment. When tubular ischemia and oxidative
      stress develop due to renal microcirculatory pathology, urinary L-type fatty acid
      binding protein (L-FABP) level increases. METHODS: Urinary L-FABP level was
      measured over time in very low-birthweight infants (VLBWI), and the effect of fat
      emulsion on L-FABP level was investigated. Thirty-one VLBWI were divided into two
      groups with regard to treatment with fat emulsion: the lipid group (n = 20) and
      the control group (n = 11). Urinary L-FABP was measured before (0-3 days of age),
      during (7-14 days of age), and after fat emulsion treatment (21-28 days of age)
      in the two groups. RESULTS: Median urinary L-FABP level before treatment was 459
      ng/mgCr (range, 22.7-5100 ng/mgCr; mean, 1067 +/- 1570 ng/mgCr) and 797 ng/mgCr
      (range, 69-3900 ng/mgCr; mean, 1066 +/- 1188 ng/mgCr) in the lipid and control
      groups, respectively, showing no significant difference. Median urinary L-FABP
      level was 624 ng/mgCr (range, 50-2050 ng/mgCr; mean +/- SD, 799 +/- 655 ng/mgCr)
      and 273 ng/mgCr (range, 31-987 ng/mgCr; mean +/- SD, 359 +/- 323 ng/mgCr) at 7-14
      days of age, respectively, showing that the level was significantly higher in the
      lipid group. At 21-28 days of age, the median level was 462 ng/mgCr (range, 49
      1867 ng/mgCr; mean +/- SD, 557 +/- 534 ng/mgCr) and 130 ng/mgCr (range, 20-993
      ng/mgCr; mean +/- SD, 290 +/- 329 ng/mgCr), respectively, showing that L-FABP
      level tended to be higher in the lipid group. CONCLUSIONS: Fat emulsion treatment
      induced a significant increase in urinary L-FABP level, suggesting that fat
      emulsion affected the proximal tubule in VLBWI.

PMID- 24106823
TI  - Pituitary and adrenal involvement in diffuse large B-cell lymphoma, with recovery
      of their function after chemotherapy.
AB  - BACKGROUND: Diffuse large B-cell lymphoma sometimes involves the endocrine
      organs, but involvement of both the pituitary and adrenal glands is extremely
      rare. Involvement of these structures can lead to hypopituitarism and adrenal
      insufficiency, and subsequent recovery of their function is rarely seen. The
      present report describes an extremely rare case of pituitary and adrenal diffuse
      large B-cell lymphoma presenting with hypopituitarism and adrenal insufficiency
      with subsequent recovery of pituitary and adrenal function after successful
      treatment of the lymphoma. CASE PRESENTATION: A 63-year-old Japanese man was
      referred to our hospital due to miosis, ptosis, hypohidrosis of his left face,
      polydipsia and polyuria. 18F-fluorodeoxy glucose positron emission tomography /
      computed tomography revealed hotspots in the pituitary gland, bilateral adrenal
      glands and the apex of his left lung. Surgical biopsy from the pituitary lesion
      confirmed the diagnosis of diffuse large B-cell lymphoma, with lymphoma cells
      replacing normal pituitary tissue. Endocrine function tests revealed adrenal
      insufficiency and panhypopituitarism, including a possible affection of the
      posterior pituitary. Hormone replacement therapy with desmopressin and
      hydrocortisone was started. Chemotherapy consisted of six courses of R-CHOP
      (rituximab, cyclophosphamide, vincristine, doxorubicin and prednisolone) and two
      courses of high-dose methotrexate followed by autologous hematopoietic stem cell
      transplantation. Subsequently, his pituitary and bilateral adrenal lesions
      resolved, and serial endocrine function tests showed gradual improvement in
      pituitary and adrenal function. CONCLUSIONS: The present report describes an
      extremely rare case of diffuse large B-cell lymphoma with involvement of both the
      pituitary and bilateral adrenal glands. R-CHOP and high-dose methotrexate therapy
      followed by autologous hematopoietic stem cell transplantation was quite
      effective, and panhypopituitarism and adrenal insufficiency improved to almost
      normal values after successful treatment of the lymphoma with chemotherapy.

PMID- 24106827
TI  - Nursing issues and concerns in the care of older persons in acute hospital care
      in the Republic of Ireland: a Delphi study.

PMID- 24106825
TI  - Cardiovascular screening in rheumatoid arthritis: a cross-sectional primary care
      database study.
AB  - BACKGROUND: Patients with rheumatoid arthritis (RA) are known to be at increased
      risk of vascular disease. It is not known whether screening for vascular risk
      factors occurs in primary care. The aim of this study was to determine whether
      guidance advocating cardiovascular screening in RA patients is being implemented
      in primary care. METHODS: This study was undertaken in a UK primary care
      consultation database. All patients with a diagnosis of RA between 2000 and 2008,
      and still registered with the GP practice in 2009 were matched by age, gender and
      GP practice to three non-RA patients. Evidence of screening for five traditional
      vascular risk factors (blood pressure, lipids, glucose, weight, smoking) was
      compared in those with and without RA using logistic regression models. A
      comparison was also made with diabetes. RESULTS: 401 RA patients were identified
      and matched to 1198 non-RA patients. No differences in the overall rates of
      screening were found (all five risk factors: RA 24.9% vs no RA 25.6%), but RA
      patients were more likely to have a smoking status recorded (67% versus 62%). In
      contrast, those with diabetes were up to 12 times as likely to receive vascular
      screening. CONCLUSIONS: Despite the excess risk of vascular disease in patients
      with RA being of a similar magnitude to that seen in diabetes, patients with RA
      did not receive additional CVD screening in primary care, although this was
      achieved in patients with diabetes. More emphasis needs to be placed on ensuring
      those with RA are actively screened for cardiovascular disease in primary care.

PMID- 24106828
TI  - On the death of Charles.

PMID- 24106829
TI  - Detection of malingering: psychometric evaluation of the Chinese version of the
      structured interview of reported symptoms-2.
AB  - BACKGROUND: Malingering detection has emerged as an important issue in clinical
      and forensic settings. The Structured Interview of Reported Symptoms-2 (SIRS-2)
      was designed to assess the feigned symptoms in both clinical and non-clinical
      subjects. The aim of the study was to examine the reliability and validity of the
      Chinese version of this scale. METHODS: Two studies were conducted to evaluate
      the reliability and validity of the Chinese Version of SIRS-2. In Study one, with
      a simulation design, the subjects included a. 40 students asked to simulate
      symptoms of mental illness; b. 40 general psychiatric inpatients and c. 40
      students asked to reply to questions honestly. Scales scores for feigning
      symptoms among three groups were carried out for discriminant validity of the
      Chinese Version of SIRS-2. Minnesota Multiphasic Personality Inventory-2(MMPI-2)
      was administered in 80 undergraduate students. In Study two, with a known-groups
      comparison design, scales scores for feigning symptoms were compared between 20
      suspected malingerers and 80 psychiatric outpatients from two forensic centers
      using the Chinese Version of SIRS-2. RESULTS: The Chinese Version of SIRS-2
      demonstrated satisfactory internal consistency in both study one and two. In
      study one, criterion validity of this scale was supported by its significantly
      positive correlation with the MMPI-2 (r = 0.282 ~ 0.481 for Infrequency), and by
      its significantly negative correlation with the MMPI-2 (r = -0.255 ~ -0.519 for
      Lie and -0.205 ~ 0.391 for Correction). Scores of 10 out of 13 subscales of the
      Chinese Version of SIRS-2 for simulators were significantly higher than scores of
      honest students and general psychiatric patients. In study two, the mean scores
      of the Chinese Version of 13 subscales for suspected malingerers were
      significantly higher than those of psychiatric outpatients. For discriminant
      validity, it yielded a large effect size (d = 1.80) for the comparison of the
      participant groups in study one and two. Moreover, the sensitivity (proportion of
      malingerers accurately identified by the measure) and specificity (proportion of
      people accurately classified as responding honestly) of the Chinese version of
      SIRS-2 in the detection of malingering in these two studies are acceptable.
      CONCLUSIONS: The Chinese version of the SIRS-2 has good psychometric properties
      and is a valid and reliable tool for detection of malingering in Chinese
      populations.

PMID- 24106830
TI  - Conformational change and ligand binding in the aristolochene synthase catalytic
      cycle.
AB  - Terpene synthases are potentially useful biocatalysts for the synthesis of
      valuable compounds, such as anticancer drugs and antibiotics. The design of
      altered activities requires better knowledge of their mechanisms, for example, an
      understanding of the complex conformational changes that are part of their
      catalytic cycle, how they are coordinated, and what drives them. Crystallographic
      studies of the sesquiterpene synthase artistolochene synthase have led to a
      proposed sequence of ligand binding and conformational change but have provided
      only indirect insight. Here, we have performed extensive molecular dynamics
      simulations of multiple enzyme-ligand complexes (over 2 MUs in total). The
      simulations provide clear evidence of what drives the conformational changes
      required for reaction. They support a picture in which the substrate farnesyl
      diphosphate binds first, followed by three magnesium ions in sequence, and, after
      reaction, the release of aristolochene and two magnesium ions followed by the
      final magnesium ion and diphosphate. Binding of farnesyl diphosphate leads to an
      increased level of sampling of open conformations, allowing the first two
      magnesium ions to bind. The closed enzyme conformation is maintained with a
      diphosphate moiety and two magnesium ions bound. The open-to-closed transition
      reduces flexibility around the active site entrance, partly through a lid closing
      over it. The simulations with all three magnesium ions and farnesyl diphosphate
      bound provide, for the first time, a realistic model of the Michaelis complex
      involved in reaction, which is inaccessible to experimental structural studies.
      These insights could help with the design of altered activities in a range of
      terpene synthases. 

PMID- 24106831
TI  - Midkine in nephrogenesis, hypertension and kidney diseases.
AB  - Midkine (MK; K; gene abbreviation, Mdk: mus musculus, MDK: homo sapiens) is a
      multifunctional heparin-binding growth factor that regulates cell growth,
      survival and migration as well as anti-apoptotic activity in nephrogenesis and
      development. Proximal tubular epithelial cells are the main sites of MK
      expression in the kidneys. The pathophysiological roles of MK are diverse,
      ranging from the development of acute kidney injury (AKI) to the progression of
      chronic kidney disease, often accompanied by hypertension, renal ischaemia and
      diabetic nephropathy. The obvious hypertension that develops in Mdk(+/+) mouse
      models of renal ablation compared with Mdk(-/-) mice eventually leads to
      progressive renal failure, such as glomerular sclerosis and tubulointerstitial
      damage associated with elevated plasma angiotensin (Ang) II levels. MK is also
      induced in the lung endothelium by oxidative stress and subsequently up-regulated
      by ACE, which hydrolyzes Ang II to induce further oxidative stress, thus
      accelerating MK generation; this leads to a vicious cycle of positive feedback in
      the MK-Ang II pathway. Kidney-lung interactions involving positive feedback
      between the renin-angiotensin system and MK might partly account for the
      pathogenesis of hypertension and kidney damage. MK is also involved in the
      pathogenesis of AKI and diabetic nephropathy through the recruitment of
      inflammatory cells. In contrast, MK plays a protective role against crescentic
      glomerulonephritis, by down-regulating plasminogen activator inhibitor-1. These
      diverse actions of MK might open up new avenues for targeted approaches to
      treating hypertension and various renal diseases. LINKED ARTICLES: This article
      is part of a themed section on Midkine. To view the other articles in this
      section visit http://dx.doi.org/10.1111/bph.2014.171.issue-4.

PMID- 24106832
TI  - In vitro antimicrobial profile of Ureaplasma urealyticum from genital tract of
      childbearing-aged women in Northern and Southern Italy.
AB  - Ureaplasma urealyticum is an opportunistic pathogen during pregnancy and in
      newborns. Other clinical problems related to U. urealyticum infections are: no
      susceptibility to cell wall-active drugs, limits of antibiotic treatment in
      pregnancy, and spread of antimicrobial resistance. In addition, the results of
      antimicrobial susceptibility against U. urealyticum from various countries are
      few and controversial. The antimicrobial susceptibility of U. urealyticum,
      isolated from cervical swabs and collected from outpatient childbearing-aged
      women in Italy from 2009 to 2012, was performed against fluoroquinolones,
      macrolides, streptogramin and tetracyclines, using an available biochemical
      commercial kit and a specific solid culture medium, to improve the therapeutic
      management of these pathogenic agents. Ureaplasma urealyticum was detected in
      49.4% of samples, but significant bacterial load was revealed in 29.8%. In vitro
      tetracyclines showed the best activity against U. urealyticum, followed by
      streptogramin, macrolides, and fluoroquinolones.

PMID- 24106833
TI  - Identification of stage-specific breast markers using quantitative proteomics.
AB  - Matched healthy and diseased tissues from breast cancer patients were analyzed by
      quantitative proteomics. By comparing proteomic profiles of fibroadenoma (benign
      tumors, three patients), DCIS (noninvasive cancer, three patients), and invasive
      ductal carcinoma (four patients), we identified protein alterations that
      correlated with breast cancer progression. Three 8-plex iTRAQ experiments
      generated an average of 826 protein identifications, of which 402 were common.
      After excluding those originating from blood, 59 proteins were significantly
      changed in tumor compared with normal tissues, with the majority associated with
      invasive carcinomas. Bioinformatics analysis identified relationships between
      proteins in this subset including roles in redox regulation, lipid transport,
      protein folding, and proteasomal degradation, with a substantial number increased
      in expression due to Myc oncogene activation. Three target proteins, cofilin-1
      and p23 (increased in invasive carcinoma) and membrane copper amine oxidase 3
      (decreased in invasive carcinoma), were subjected to further validation. All
      three were observed in phenotype-specific breast cancer cell lines, normal
      (nontransformed) breast cell lines, and primary breast epithelial cells by
      Western blotting, but only cofilin-1 and p23 were detected by multiple reaction
      monitoring mass spectrometry analysis. All three proteins were detected by both
      analytical approaches in matched tissue biopsies emulating the response observed
      with proteomics analysis. Tissue microarray analysis (361 patients) indicated
      cofilin-1 staining positively correlating with tumor grade and p23 staining with
      ER positive status; both therefore merit further investigation as potential
      biomarkers. 

PMID- 24106834
TI  - Beyond the fringe: when science moves from innovative to nonsense.
AB  - Microbiology has experienced examples of highly productive researchers who have
      gone beyond just interpreting their experimental results with hypotheses and
      published nonsense that was readily recognized as such by readers. Although the
      most discussed cases of this pathology come from physics, studies of single
      celled microorganisms, virology, and immunology have provided many examples. Five
      cases are described here along with some generalizations. These are the
      Lamarckian inheritance of acquired characteristics reported by distinguished and
      experienced researchers, vectorless DNA transfer and incorporation of bacterial
      DNA into chromosomes of plants years before vector construction of genetically
      modified plants was invented, water with memory of immunoglobulin IgE, a new
      electromagnetic radiation method for identifying bacterial and viral pathogens by
      the discoverer of human immunodeficiency virus, and the claim of isolation of a
      new bacterial isolate with arsenic replacing phosphorus in DNA. These examples
      represent very dissimilar areas, and the only common factor is hubris on the part
      of experienced researchers. Secondarily, failure of peer review sometimes
      happens, and journal editors do not step in, sometimes even when alerted before
      publication. These failures of the publishing process teach us that unnecessary
      mistakes occur and should warn us all to watch our own enthusiasms. 

PMID- 24106837
TI  - Normal neutrophil myosin IIA localization in an immunofluorescence analysis can
      rule out MYH9 disorders.

PMID- 24106838
TI  - Turkish experience in rheumatoid arthritis patients with clinical apparent
      amyloid deposition.
AB  - OBJECTIVES: We evaluated the frequency of clinical apparent amyloid deposition,
      clinical features and outcome in our rheumatoid arthritis (RA) patients. METHODS:
      Medical records of 1415 RA patients were examined. During routine follow-up, RA
      patients with proteinuria on urinalysis, underwent rectal biopsy. RESULTS: Eleven
      patients (0.78%) were diagnosed with clinical apparent amyloid deposition. While
      the mean annual incidence of AA amyloidosis between 2001 and 2005 was 0.2%, it
      was 0.13% between 2006 and 2011. At initial presentation, three RA-related AA
      amyloidosis patients had nephrotic-range proteinuria and renal insufficiency,
      four had only nephrotic-range proteinuria, three had non-nephrotic-range
      proteinuria, and one had non-nephrotic-range proteinuria and renal insufficiency.
      The mean age in RA patients with AA amyloidosis was 60.8 years and disease
      duration was 12 years. Ten of 11 cases had positive rheumatoid factor. Two RA
      patients with AA amyloidosis who had been diagnosed in the pre-anti-TNF era died.
      Of the rest nine patients with AA amyloidosis, eight were administered anti-TNF
      therapy and one was given rituximab. In four patients, anti-TNF therapy led to
      disappearance of clinical features, decrement in proteinuria and resulted in
      improvement of or at least stabilization of renal functions. One patient using
      anti-TNF therapy died because of tuberculosis. One patient discontinued anti-TNF
      therapy and developed end-stage renal disease. Two patients have been started to
      be given anti-TNF therapy recently. In one patient who was given rituximab, there
      was regression of proteinuria and improvement in renal functions. CONCLUSIONS: We
      diagnosed a 0.78% frequency of AA amyloidosis in RA. It seems that - other than
      the risks of infection, tuberculosis - anti-TNF drugs seem to be effective on RA
      disease activity and also have renoprotective effects in RA patients with AA
      amyloidosis.

PMID- 24106840
TI  - Antibiotic uptake by vegetable crops from manure-applied soils.
AB  - This study quantified the uptake of five antibiotics (chlortetracycline,
      monensin, sulfamethazine, tylosin, and virginiamycin) by 11 vegetable crops in
      two different soils that were fertilized with raw versus composted turkey and hog
      manures or inorganic fertilizer. Almost all vegetables showed some uptake of
      antibiotics from manure treatments. However, statistical testing showed that
      except for a few isolated treatments the concentrations of all antibiotics in
      vegetable tissues were generally less than the limits of quantification. Further
      testing of the significant treatments showed that antibiotic concentrations in
      vegetables from many of these treatments were not significantly different than
      the corresponding concentrations from the fertilizer treatment (matrix effect).
      All five antibiotic concentrations in the studied vegetables were <10 MUg kg(-1).
      On the basis of the standards for maximum residue levels in animal tissues and
      suggested maximum daily intake based on body weight, this concentration would not
      pose any health risk unless one is allergic to that particular antibiotic. 

PMID- 24106839
TI  - Conformation-selective inhibitors reveal differences in the activation and
      phosphate-binding loops of the tyrosine kinases Abl and Src.
AB  - Over the past decade, an increasingly diverse array of potent and selective
      inhibitors that target the ATP-binding sites of protein kinases have been
      developed. Many of these inhibitors, like the clinically approved drug imatinib
      (Gleevec), stabilize a specific catalytically inactive ATP-binding site
      conformation of their kinases targets. Imatinib is notable in that it is highly
      selective for its kinase target, Abl, over other closely related tyrosine
      kinases, such as Src. In addition, imatinib is highly sensitive to the
      phosphorylation state of Abl's activation loop, which is believed to be a general
      characteristic of all inhibitors that stabilize a similar inactive ATP-binding
      site conformation. In this report, we perform a systematic analysis of a diverse
      series of ATP-competitive inhibitors that stabilize a similar inactive ATP
      binding site conformation as imatinib with the tyrosine kinases Src and Abl. In
      contrast to imatinib, many of these inhibitors have very similar potencies
      against Src and Abl. Furthermore, only a subset of this class of inhibitors is
      sensitive to the phosphorylation state of the activation loop of these kinases.
      In attempting to explain this observation, we have uncovered an unexpected
      correlation between Abl's activation loop and another flexible active site
      feature, called the phosphate-binding loop (p-loop). These studies shed light on
      how imatinib is able to obtain its high target selectivity and reveal how the
      conformational preference of flexible active site regions can vary between
      closely related kinases. 

PMID- 24106841
TI  - Evaluation of the living with hope program for rural women caregivers of persons
      with advanced cancer.
AB  - BACKGROUND: Hope has been identified as a key psychosocial resource among family
      caregivers to manage and deal with the caregiver experience. The Living with Hope
      Program is a self-administered intervention that consists of watching an
      international award winning Living with Hope film and participating in a two week
      hope activity ("Stories of the Present"). The purpose of this study was to
      examine the effects of the Living with Hope Program on self-efficacy [General
      Self-Efficacy Scale], loss and grief [Non-Death Revised Grief Experience
      Inventory], hope [Herth Hope Index] and quality of life [Short-Form 12 version 2
      (SF-12v2)] in rural women caring for persons with advanced cancer and to model
      potential mechanisms through which changes occurred. METHODS: A time-series
      embedded mixed method design was used, with quantitative baseline outcome
      measures repeated at day 7, day 14, and 3, 6 and 12 months. Qualitative data from
      the hope activity informed the quantitative data. Thirty-six participants agreed
      to participate with 22 completing all data collection. General estimating
      equations were used to analyze the data. RESULTS: Herth Hope Index scores
      (p=0.05) had increased significantly from baseline at day 7. General Self
      Efficacy Scale scores were significantly higher than baseline at all data time
      points. To determine the mechanisms of the Living with Hope Program through which
      changes occurred, results of the data analysis suggested that as General Self
      Efficacy Scale scores increased (p<0.001) and Non-death Revised Grief Experience
      Inventory scores decreased (p=0.01) Herth Hope Index scores increased. In
      addition as Herth Hope Index scores increased (p<0.001) and Non-death Revised
      Grief Experience Inventory scores decreased (p=0.01), SF-12v2 mental health
      summary scores increased. Qualitative data suggested that through the hope
      activity (Stories of the Present) the participants were able to find positives
      and hope in their experience. CONCLUSIONS: The Living with Hope Program has
      potential to increase hope and improve quality of life for rural women caregivers
      of persons with advanced cancer. The possible mechanisms by which changes in hope
      and quality of life occur are by decreasing loss and grief and increasing self
      efficacy. TRIAL REGISTRATIONS: Registration ClinicalTrials.gov, NCT01081301.

PMID- 24106843
TI  - Give staff the good news too.

PMID- 24106842
TI  - Influenza pneumonia among adolescents and adults: a concurrent comparison between
      influenza A (H1N1) pdm09 and A (H3N2) in the post-pandemic period.
AB  - INTRODUCTION: Comparisons of the characteristics between the influenza A (H1N1)
      pdm09 and common seasonal influenza are important for both clinical management
      and epidemiological studies. However, the differences between pandemic and
      seasonal influenza during the post-pandemic period are poorly understood.
      OBJECTIVES: The aim of our research was to investigate clinical and immune
      response differences between patients with influenza A (H1N1) pdm09 pneumonia and
      seasonal influenza A (H3N2) pneumonia in the post-pandemic period. METHODS:
      During the first flu season in post-pandemic period, patients from Beijing
      Network for Adult Community-Acquired Pneumonia present A (H1N1) pdm09 or A (H3N2)
      influenza were compared concurrently in the aspects of clinical characteristics
      and inflammatory profile in acute phase. RESULT: Patients with A (H1N1) pdm09
      influenza pneumonia showed a close mean age to A (H3N2) pneumonia (51 +/- 20 vs
      53 +/- 16, mean +/- standard deviation, years) but tended to have more underlying
      diseases (32.8% vs 10%, P=0.036). Although clinical characteristics were similar,
      no statistical difference were found in pneumonia severity index (PSI) score or
      intensive care unit admission rate or mortality, patients in A (H1N1) pdm09
      cohort present higher levels of aspartate aminotransferase, lactase dehydrogenase
      (P=0.006, 0.018, respectively) in blood and also longer duration of fever than A
      (H3N2) cohort. Levels of interleukin (IL)-10 and IL-12 (p70) were higher in A
      (H1N1) pdm09 cohort (P=0.031, 0.047, respectively). CONCLUSIOS: During the first
      post-pandemic flu season, patients with the A (H1N1) pdm09 pneumonia showed
      similar clinical characteristics but slightly higher disease severity and
      stronger systemic inflammatory response than A (H3N2) pneumonia.

PMID- 24106848
TI  - College calls for investment in emergency departments.

PMID- 24106851
TI  - Deaths from severe sepsis due to care failures, report claims.

PMID- 24106852
TI  - More nurses to help police manage people with mental health problems.

PMID- 24106853
TI  - Board's eye view.

PMID- 24106854
TI  - Ending the care lottery.

PMID- 24106859
TI  - Setting up an alcohol treatment centre.
AB  - In the emergency unit at University Hospital of Wales (UHW), Cardiff, a rise in
      the number of patients presenting with alcohol intoxication was reducing the
      amount of clinical space available to, and affecting the care of, other patients.
      In response, an alcohol treatment centre (ATC) staffed by emergency nurse
      practitioners, healthcare assistants and police officers was set up and piloted
      for three months in the city centre to ensure that people who were severely
      intoxicated could be managed safely without attending the emergency unit at UHW.
      This article describes the collaborative approach adopted to launch the three
      month pilot project and discusses findings from a review of the ATC conducted
      when the pilot had ended. These findings indicate that severely intoxicated
      patients at low or moderate risk had been diverted from the emergency unit to the
      ATC and that clinical care in the unit, and police and ambulance services, had
      improved as a result. 

PMID- 24106860
TI  - Patient safety and nurses' role in procedural sedation.
AB  - In the United States, following the singer Michael Jackson's fatal overdose of
      the sedative propofol in 2009, there has been extensive controversy about the
      administration of the drug by nurses during procedural sedation, or sedation
      during specific procedures that physicians can suspend to assist nurses in airway
      management. This article reviews the evidence base for nurses administering
      procedural sedation under medical supervision. 

PMID- 24106861
TI  - Why people complain after attending emergency departments.
AB  - Complaints are a vital component of clinical governance in healthcare systems. In
      a patient-focused NHS, it is important that healthcare professionals and
      organisations listen to, and act on, complaints from people who think they have
      been let down by the services they have received. This article reports on the
      results of a study of what prompts patients to complain after attending an
      emergency department (ED). As the results show, the complaint rate was 0.04 per
      cent. Among reasons why patients complained, non-clinical issues (63 per cent),
      such as poor communication and staff attitudes, and long waiting times, outnumber
      clinical issues (37 per cent). The study also highlights the need for greater
      direct supervision of junior staff, although this could be challenging given the
      current workforce pressures facing UK EDs. 

PMID- 24106862
TI  - Communicating with people who have experienced heart attack.
AB  - Presentations of acute myocardial infarction (MI) can be divided into diagnostic
      subcategories that require different treatments. This article reports the results
      of a study that explored and compared patients' perceptions of their illness and
      motivation for behavioural change after different treatments for MI. Results
      suggest that patients who have had non-ST elevation MI (NSTEMI) and whose initial
      diagnosis is uncertain take their condition less seriously than those who have
      had STEMI and invasive or 'urgent' treatments. This tendency can make them less
      motivated to change their lifestyles. Healthcare professionals in emergency
      departments should be aware of, and address, patients' misconceptions and provide
      clear and consistent advice to improve their long-term outcomes. 

PMID- 24106863
TI  - Passion for care.
AB  - Through a combination of shift work and international clinical assistance,
      medical trainer and nurse Richard Baldry has obtained invaluable skills and
      insights in emergency care. He now works for International SOS, which provides
      medical assistance to corporate business travellers and expatriates around the
      world. Carol Davis reports on his career. 

PMID- 24106864
TI  - A best practice fall prevention exercise program to improve balance, strength /
      power, and psychosocial health in older adults: study protocol for a randomized
      controlled trial.
AB  - BACKGROUND: With increasing age neuromuscular deficits (e.g., sarcopenia) may
      result in impaired physical performance and an increased risk for falls.
      Prominent intrinsic fall-risk factors are age-related decreases in balance and
      strength / power performance as well as cognitive decline. Additional studies are
      needed to develop specifically tailored exercise programs for older adults that
      can easily be implemented into clinical practice. Thus, the objective of the
      present trial is to assess the effects of a fall prevention program that was
      developed by an interdisciplinary expert panel on measures of balance, strength /
      power, body composition, cognition, psychosocial well-being, and falls self
      efficacy in healthy older adults. Additionally, the time-related effects of
      detraining are tested. METHODS/DESIGN: Healthy old people (n = 54) between the
      age of 65 to 80 years will participate in this trial. The testing protocol
      comprises tests for the assessment of static / dynamic steady-state balance
      (i.e., Sharpened Romberg Test, instrumented gait analysis), proactive balance
      (i.e., Functional Reach Test; Timed Up and Go Test), reactive balance (i.e.,
      perturbation test during bipedal stance; Push and Release Test), strength (i.e.,
      hand grip strength test; Chair Stand Test), and power (i.e., Stair Climb Power
      Test; countermovement jump). Further, body composition will be analysed using a
      bioelectrical impedance analysis system. In addition, questionnaires for the
      assessment of psychosocial (i.e., World Health Organisation Quality of Life
      Assessment-Bref), cognitive (i.e., Mini Mental State Examination), and fall risk
      determinants (i.e., Fall Efficacy Scale - International) will be included in the
      study protocol. Participants will be randomized into two intervention groups or
      the control / waiting group. After baseline measures, participants in the
      intervention groups will conduct a 12-week balance and strength / power exercise
      intervention 3 times per week, with each training session lasting 30 min. (actual
      training time). One intervention group will complete an extensive supervised
      training program, while the other intervention group will complete a short
      version ('3 times 3') that is home-based and controlled by weekly phone calls.
      Post-tests will be conducted right after the intervention period. Additionally,
      detraining effects will be measured 12 weeks after program cessation. The control
      group / waiting group will not participate in any specific intervention during
      the experimental period, but will receive the extensive supervised program after
      the experimental period. DISCUSSION: It is expected that particularly the
      supervised combination of balance and strength / power training will improve
      performance in variables of balance, strength / power, body composition,
      cognitive function, psychosocial well-being, and falls self-efficacy of older
      adults. In addition, information regarding fall risk assessment, dose-response
      relations, detraining effects, and supervision of training will be provided.
      Further, training-induced health-relevant changes, such as improved performance
      in activities of daily living, cognitive function, and quality of life, as well
      as a reduced risk for falls may help to lower costs in the health care system.
      Finally, practitioners, therapists, and instructors will be provided with a
      scientifically evaluated feasible, safe, and easy-to-administer exercise program
      for fall prevention.

PMID- 24106867
TI  - Practices that reduce the Latina survival disparity after breast cancer.
AB  - OBJECTIVES: Latina breast cancer patients are 20 percent more likely to die
      within 5 years after diagnosis compared with white women, even though they have a
      lower incidence of breast cancer, lower general mortality rates, and some better
      health behaviors. Existing data only examine disparities in the utilization of
      breast cancer care; this research expands the study question to which utilization
      factors drive the shorter survival in Latina women compared with white women.
      METHODS: This longitudinal linked Surveillance Epidemiology and End Results
      (SEER)-Medicare cohort study examined early stage breast cancer patients
      diagnosed between 1992 and 2000 and followed for 5-11 years after diagnosis
      (N=44,999). Modifiable utilization factors included consistent visits to primary
      care providers and to specialists after diagnosis, consistent post-diagnosis
      mammograms, and receipt of initial care consistent with current standards of
      care. RESULTS: Of the four utilization factors potentially driving this
      disparity, a lack of consistent post-diagnosis mammograms was the strongest
      driver of the Latina breast cancer survival disparity. Consistent mammograms
      attenuated the hazard of death from 23% [hazard ratio, HR, (95% confidence
      interval, 95%CI)=1.23 (1.1,1.4)] to a nonsignificant 12% [HR (95%CI)=1.12
      (0.7,1.3)] and reduced the excess hazard of death in Latina women by 55%. Effect
      modification identified that visits to primary care providers have a greater
      protective impact on the survival of Latina compared to white women [HR
      (95%CI)=0.9 (0.9,0.9)]. CONCLUSIONS: We provide evidence that undetected new or
      recurrent breast cancers due to less consistent post-diagnosis mammograms
      contribute substantially to the long-observed Latina survival disadvantage.
      Interventions involving primary care providers may be especially beneficial to
      this population.

PMID- 24106868
TI  - Stress urinary incontinence in younger women in primary care: prevalence and
      opportunistic intervention.
AB  - BACKGROUND: Stress urinary incontinence (SUI) is prevalent in females, even among
      young adults. Though their quality of life (QOL) is impaired and pelvic floor
      exercise is an effective treatment, not many affected women seek medical help.
      This study aimed to evaluate the feasibility of case finding and opportunistic
      intervention of SUI at a public Well Women Clinic in Macau, China. METHOD: A
      convenience sample of 408 consecutive female patients aged 30-50 years filled in
      the Urogenital Distress Inventory Short Form and the Incontinence Impact
      Questionnaire Short Form. They were also asked reasons for not seeking for
      medical help. The patients with incontinence were educated on pelvic floor muscle
      exercise during the gynecological examination. RESULTS: SUI was reported by 153
      (37.5%) women, of whom 47 (30.7%) had impaired quality of life despite mild
      symptoms. Of the SUI patients, 52.9% thought that incontinence was inevitable
      with age, 22.2% believed that they should cope with the problem themselves, 13.7%
      thought that no useful treatment was available, and 3.9% had sought medical
      advice before. After learning pelvic floor muscle exercise for 4 to 6 months,
      9.8% of SUI patients had complete relief of the symptoms, 47% partial
      improvement, and 17.6% no significant change. CONCLUSIONS: SUI with impaired
      quality of life was common before menopause. Very few affected women sought
      medical help. Opportunistic case finding and education about pelvic floor
      exercise in a Well Women Clinic were effective in the detection and treatment of
      the silent SUI.

PMID- 24106869
TI  - The prognostic significance of perineural invasion and race in men considering
      active surveillance.
AB  - OBJECTIVE: To determine the importance of perineural invasion (PNI) on diagnostic
      biopsy in men enrolled in active surveillance (AS). PATIENTS AND METHODS:
      Eligibility criteria for AS included clinical stage <= T2a and Gleason score <=6,
      <=3 cores positive, maximum single core involvement <50%, and total tumour volume
      <=5% on diagnostic biopsy. All men received 12-core confirmation biopsy at <=6
      months. AS 'failure' on confirmatory biopsy was defined as failure to meet one or
      more eligibility criteria. Risk of AS failure was compared in men with and
      without PNI. RESULTS: For the 165 men comprising the study population, the mean
      (sd) age was 66.9 (6.5) years and the median (interquartile, IQR) PSA level of
      men at study entry was 4.4 (3.2-6.0) ng/mL. The median (IQR) follow-up was 5.5
      (1.1-9.9) months. In all, 8.5% (14/165 men) had PNI on diagnostic biopsy.
      Compared with those without PNI, men with PNI tended to have more cores involved
      with cancer, at a mean (sd) of 2.0 (0.7) vs 1.6 (0.8) cores (P = 0.08) but did
      not have significantly a greater mean (sd) total tumour length on diagnostic
      biopsy, at 3.0 (2.1) vs 2.3 (3.6) mm (P = 0.27). Men with PNI on diagnostic
      biopsy were significantly more likely to meet criteria for disease progression on
      confirmatory biopsy (57% [8/14] vs 21% [32/151]; P = 0.006). PNI remained a
      significant predictor for AS failure after adjustment for number of positive
      cores, maximum percentage core involvement, and total tumour length (odds ratio
      4.4, 95% confidence interval 1.4-14.2). CONCLUSIONS: PNI on diagnostic biopsy is
      associated with disease progression on confirmatory biopsy. The presence of PNI
      should factor into appropriate patient selection and counselling in AS.

PMID- 24106870
TI  - miRNA in mycosis fungoides and skin inflammation.
AB  - In this mini-review, progress in our understanding of the link between miRNAs and
      cytokines in inflammatory skin diseases is highlighted with focus on miR-155 in
      mycosis fungoides (MF). MF is the most common variant of cutaneous T-cell
      lymphoma (CTCL) and is characterized by malignant T-cell proliferation in a
      chronic inflammatory environment in affected skin. Recent data show that miR-155
      is expressed in situ by both malignant and non-malignant T cells, induced via the
      STAT5 signal pathway and IL-2Rbeta/gamma cytokines, and thus suggest the
      importance of miR-155 in malignant proliferation, clinical diagnosis, and
      prognosis in CTCL. 

PMID- 24106871
TI  - Elastin binding protein and FKBP65 modulate in vitro self-assembly of human
      tropoelastin.
AB  - Elastin is a protein that provides the unusual properties of extensibility and
      elastic recoil to tissues. Assembly of polymeric elastin into its final
      architecture in the extracellular matrix involves both self-aggregation
      properties of its monomeric precursor, tropoelastin, and interactions with
      several matrix-associated proteins that appear to act by modulating the intrinsic
      self-assembly of tropoelastin. Because of its highly nonpolar character and
      propensity to self-aggregate, it has been suggested that mechanisms limiting self
      aggregation must also be present during the transit of tropoelastin through the
      cell prior to secretion. Both the elastin binding protein (EBP) and FKBP65 have
      been suggested to fulfill that role in the Golgi and endoplasmic reticulum
      compartments of the cell, respectively. However, details about the nature of the
      interactions between these proteins as well as about the mechanism by which they
      may act to limit self-aggregation are lacking. In this study, we demonstrate that
      both EBP and FKBP65 have strong binding affinities for tropoelastin, with the
      dissociation constant of EBP approximately 4-fold lower than that of FKBP65. Both
      proteins also modify the kinetics of self-assembly of tropoelastin in an in vitro
      system, consistent with a role in attenuating the premature intracellular self
      aggregation of tropoelastin through a mechanism that limits the growth and
      maturation of aggregates. The ability of FKBP65 to modulate the self-assembly of
      tropoelastin is independent of its enzymatic activity to promote the cis-trans
      isomerization of proline residues in proteins.

PMID- 24106873
TI  - Why is melanoma so metastatic?
AB  - Malignant melanoma is one of the most aggressive cancers and can disseminate from
      a relatively small primary tumor and metastasize to multiple sites, including the
      lung, liver, brain, bone, and lymph nodes. Elucidating the molecular and genetic
      changes that take place during the metastatic process has led to a better
      understanding of why melanoma is so metastatic. Herein, we describe the unique
      features that distinguish melanoma from other solid tumors and contribute to the
      malignant phenotype of melanoma cells. For example, although melanoma cells are
      highly antigenic, they are extremely efficient at evading host immune response.
      Melanoma cells share numerous cell surface molecules with vascular cells, are
      highly angiogenic, are mesenchymal in nature, and possess a higher degree of
      'stemness' than do other solid tumors. Finally, analysis of melanoma mutations
      has revealed that the gene expression profile of malignant melanoma is different
      from that of other cancers. Elucidating these molecular and genetic processes in
      highly metastatic melanoma can lead to the development of improved treatment and
      individualized therapy options. 

PMID- 24106872
TI  - Single doses of THC and cocaine decrease proficiency of impulse control in heavy
      cannabis users.
AB  - BACKGROUND AND PURPOSE: Cannabis is the most popular drug used in the European
      Union, closely followed by cocaine. Whereas cannabis impairs neurocognitive
      function in occasional cannabis users, such impairments appear less prominent in
      heavy users, possibly as a result of tolerance. The present study was designed to
      assess whether the impairing effects of Delta(9) -tetrahydrocannabinol (THC) in
      heavy cannabis users would present in a wide range of neuropsychological
      functions or selectively affect specific performance domains. We also assessed
      the acute effects of cocaine on neurocognitive functions of heavy cannabis users.
      EXPERIMENTAL APPROACH: Heavy cannabis users, who had a history of cocaine use (n
      = 61), participated in a double-blind, placebo-controlled, three-way crossover
      study. Subjects received single doses of cocaine HCl (300 mg), cannabis (THC
      MUg.kg(-1) ) and placebo, and completed a number of tests measuring impulse
      control and psychomotor function. KEY RESULTS: Single doses of cannabis impaired
      psychomotor function and increased response errors during impulsivity tasks.
      Single doses of cocaine improved psychomotor function and decreased response time
      in impulsivity tasks, but increased errors. CONCLUSIONS AND IMPLICATIONS: Heavy
      cannabis users display impairments in a broad range of neuropsychological domains
      during THC intoxication. Impairments observed in psychomotor tasks, but not in
      impulsivity tasks, appeared smaller in magnitude as compared with those
      previously reported in occasional cannabis users. Heavy cannabis users were
      sensitive to the stimulating and inhibitory effects of cocaine on psychomotor
      function and impulsivity respectively. The reduction in proficiency in impulse
      control may put drug users at increased risk of repeated drug use and addiction.

PMID- 24106874
TI  - Epidemiological study and considerations of primary focal hyperhidrosis in Japan:
      from questionnaire analysis.
AB  - Primary hyperhidrosis is a disorder of excessive, bilateral and relatively
      symmetrical sweating occurring in the palms, soles and axillae regions without
      obvious etiology. There have been some reports of the epidemiology of primary
      hyperhidrosis abroad so far, but there has never been any research performed in
      Japan. We performed a questionnaire survey for people aged 5-64 years who agreed
      with the purpose of this study at 20 companies or schools, and received 5807
      valid responses. From this survey, each prevalence could broken down into 5.33%
      for primary palm hyperhidrosis, 2.79% for primary plantar hyperhidrosis, 5.75%
      for primary axillae hyperhidrosis and 4.7% for primary head hyperhidrosis.
      Patients with severe symptoms were estimated to be approximately 616,000 for
      primary palmar hyperhidrosis and 2,239,000 for primary axillae hyperhidrosis in
      Japan. These findings reveal that many patients feel a decreased quality of life
      because of symptoms of hyperhidrosis every day. However, only 6.2% of the
      patients had visited medical institutions. Moreover, few patients take
      appropriate treatment even after visiting the hospital.

PMID- 24106875
TI  - Insulin plus incretin agent combination therapy in type 2 diabetes: a systematic
      review.
AB  - BACKGROUND: Insulin and incretin agents (dipeptidyl peptidase-4 inhibitors
      [DPP4is] and glucagon-like peptide-1 receptor agonists [GLP1 RAs]) are second
      line treatment options in patients with type 2 diabetes (T2D) not achieving
      glycemic targets with metformin. Combinations of insulin with incretin agents
      have been explored in randomized controlled trials (RCTs) and retrospective
      studies. However, the optimal approach is still elusive; numerous combination
      regimens can be envisioned, differing in composition and in order of addition.
      SCOPE: A systematic survey was conducted of RCTs testing insulin/DPP4i or
      insulin/GLP1 RA regimens. PubMed and other online databases were queried using
      'insulin' and the names of all incretin agents available in Canada, along with
      'combination', 'concomitant', 'concurrent', and 'add-on'. Web of Science and
      clinicaltrials.gov were searched to identify unpublished trials. FINDINGS:
      Fifteen placebo-controlled or active-comparator RCTs were identified, reporting
      outcomes for regimens combining insulins and incretin agents available in Canada.
      DPP4i add-on to insulin therapy (six trials) leads to modest A1c lowering, with
      weight neutrality. GLP1 RA and insulin combination therapy (GLP1 RA add-on, five
      trials; insulin add-on, two trials) is associated with significant A1c lowering,
      with beneficial effects on body weight. A single proof-of-concept trial compared
      GLP1 RA to DPP4i add-on to insulin, and only one RCT examined simultaneous
      introduction of an incretin agent with insulin. Adding an incretin agent to
      established basal insulin therapy may represent a useful alternative to insulin
      intensification with prandial or premixed insulin. Initial introduction of an
      incretin agent, with subsequent introduction of insulin, offers potential
      practical advantages. No study directly comparing order of addition has yet been
      reported. CONCLUSIONS: Insulin/incretin combination therapy comprises a variety
      of efficacious, weight-sparing regimens and may be considered for many patients
      who do not achieve glycemic targets when treated with insulin or an incretin
      agent.

PMID- 24106876
TI  - Isolation and partial characterization of bacteria (Pseudoalteromonas sp.) with
      potential antibacterial activity from a marine costal environment from New
      Caledonia.
AB  - Marine bacteria are a rich source of bioactive metabolites. However, the
      microbial diversity of marine ecosystem still needs to be explored. The aim of
      this study was to isolate and characterize bacteria with antimicrobial activities
      from various marine coastal environment of New Caledonia. We obtained 493 marine
      isolates from various environments and samples of which 63 (12.8%) presented an
      antibacterial activity against a panel of reference pathogenic strains
      (Staphylococcus aureus, Pseudomonas aeruginosa, Escherichia coli and Enterococcus
      faecalis). Ten out of the most promising strains were cultured, fractionated and
      screened for antibacterial activity. Four of them (NC282, NC412, NC272 and NC120)
      showed at least an activity against reference and multidrug-resistant pathogenic
      strains and were found to belong to the genus Pseudoalteromonas, according to the
      16S phylogenetic analysis. The NC282 strain does not belong to any described
      Pseudoalteromonas species and might be of interest for further chemical and
      biological characterization. These findings suggest that the identified strains
      may contribute to the discovery for new sources of antimicrobial substances to
      develop new therapies to treat infections caused by multidrug-resistant bacteria.
      SIGNIFICANCE AND IMPACT OF THE STUDY: With the constant increasing of bacterial
      resistance against known antibiotics in worldwide public health, it is now
      necessary to find new sources of antimicrobials. Marine bacteria from New
      Caledonia were isolated, tested for antibacterial activity and characterized to
      find new active molecules against multidrug-resistant bacteria. This study
      illustrates the diversity of the marine ecosystem with potent new bacteria
      species. Also the potential of marine bacteria as a rich source of bioactive
      molecule, for example antibiotics, is highlighted.

PMID- 24106877
TI  - Retention and remobilization of stabilized silver nanoparticles in an undisturbed
      loamy sand soil.
AB  - Column experiments were conducted with undisturbed loamy sand soil under
      unsaturated conditions (around 90% saturation degree) to investigate the
      retention of surfactant stabilized silver nanoparticles (AgNPs) with various
      input concentration (Co), flow velocity, and ionic strength (IS), and the
      remobilization of AgNPs by changing the cation type and IS. The mobility of AgNPs
      in soil was enhanced with decreasing solution IS, increasing flow rate and input
      concentration. Significant retardation of AgNP breakthrough and hyperexponential
      retention profiles (RPs) were observed in almost all the transport experiments.
      The retention of AgNPs was successfully analyzed using a numerical model that
      accounted for time- and depth-dependent retention. The simulated retention rate
      coefficient (k1) and maximum retained concentration on the solid phase (Smax)
      increased with increasing IS and decreasing Co. The high k1 resulted in retarded
      breakthrough curves (BTCs) until Smax was filled and then high effluent
      concentrations were obtained. Hyperexponential RPs were likely caused by the
      hydrodynamics at the column inlet which produced a concentrated AgNP flux to the
      solid surface. Higher IS and lower Co produced more hyperexponential RPs because
      of larger values of Smax. Retention of AgNPs was much more pronounced in the
      presence of Ca(2+) than K(+) at the same IS, and the amount of AgNP released with
      a reduction in IS was larger for K(+) than Ca(2+) systems. These stronger AgNP
      interactions in the presence of Ca(2+) were attributed to cation bridging.
      Further release of AgNPs and clay from the soil was induced by cation exchange
      (K(+) for Ca(2+)) that reduced the bridging interaction and IS reduction that
      expanded the electrical double layer. Transmission electron microscopy, energy
      dispersive X-ray spectroscopy, and correlations between released soil colloids
      and AgNPs indicated that some of the released AgNPs were associated with the
      released clay fraction. 

PMID- 24106878
TI  - Design of metastable beta-sheet oligomers from natively unstructured peptide.
AB  - Amyloid oligomers represent the primary pathological species for
      neurodegenerative diseases such as Alzheimer's and Parkinson's diseases. Toxic
      oligomers are formed by many different proteins and peptides, but their
      polydispersity makes them highly dynamic and heterogeneous. One way to stabilize
      these structures is to prepare constrained peptides that can be used to study
      amyloid intermediates, to identify oligomer-specific drugs, and to generate
      conformational antibodies. These conformational antibodies have demonstrated that
      oligomers share a common epitope. In this research, we used a 40-amino acid
      unstructured segment of prion protein (Prp) 109-148 with substitutions of
      methionine for glycine (Prp-G) residues to prepare a stable and homogeneous
      population of beta-sheet oligomer mimics. These structures were characterized by
      multiple biophysical and biochemical techniques that show characteristic features
      of oligomers. Finally, this preparation was not detected by three different
      sequence dependent prion antibodies. 

PMID- 24106879
TI  - An exploration of risk for recurrent falls in two geriatric care settings.
AB  - BACKGROUND: Fall events were examined in two distinct geriatric populations to
      identify factors associated with repeat fallers, and to examine whether patients
      who use gait aids, specifically a walker, were more likely to experience repeat
      falls. Each unit already had a generic program for falls prevention in place.
      METHODS: Secondary data analysis was conducted on information collected during
      the pilot testing of a new quality assurance Incident Reporting Tool between
      October 2006 and September 2008. The study settings included an in-patient
      geriatric rehabilitation unit (GRU) and a long stay veterans' unit (LSVU) in a
      rehabilitation and long-stay hospital in Ontario. Participants were two hundred
      and twenty three individuals, aged 65 years or older on these two units, who
      experienced one or more fall incidents during the study period. RESULTS: Logistic
      regression analyses showed that on the GRU age was significantly associated with
      repeat falls. On the LSVU first falls in the morning or late evening were
      associated with repeat falling. Walker as a gait aid listed at time of first fall
      was not associated with repeat falls. CONCLUSIONS: This study suggests that
      different intervention may be necessary in different geriatric settings to
      identify, for secondary prevention, certain individuals for which the generic
      programs prove inadequate. Information collection with a specific focus on the
      issue of repeat falls may be necessary for greater insight.

PMID- 24106880
TI  - A pilot evaluation of an educational program that offers visualizations of
      cervical spine injuries: medical students' self-efficacy increases by training.
AB  - In this pilot study, a new method for visualization through imaging and
      simulation (VIS-Ed) for teaching diagnosis and treatment of cervical spine trauma
      was formatively evaluated. The aims were to examine if medical students' self
      efficacy would change by training using VIS-Ed, and if so these changes were
      related to how they evaluated the session, and the user interface (UI) of this
      program. Using a one-group, pre-post course test design 43 Swedish medical
      students (4th year, 17 males, 26 females) practiced in groups of three
      participants. Overall the practice and the UI were considered as positive
      experiences. They judged VIS-Ed as a good interactive scenario-based educational
      tool. All students' self-efficacy increased significantly by training (p <
      0.001). Spearman's rank correlation tests revealed that increased self-efficacy
      was only associated with: how the session was compared to as expected (p <
      0.007). Students' self-efficacy increased significantly by training, but
      replication studies should determine if this training effect is gender-related. 

PMID- 24106881
TI  - Novel medium-term carcinogenesis model for lung squamous cell carcinoma induced
      by N-nitroso-tris-chloroethylurea in mice.
AB  - Targeted treatments for lung cancer based on pathological diagnoses are required
      to enhance therapeutic efficacy. There are few well-established animal models for
      lung squamous cell carcinoma although several highly reproducible mouse models
      for lung adenoma and adenocarcinoma are available. This study was carried out to
      establish a new lung squamous cell carcinoma mouse model. In the first
      experiment, female A/J mice were painted topically on back skin twice weekly with
      75 MUL 0.013 M N-nitroso-tris-chloroethylurea for 2, 4, and 8 weeks (n = 15-20
      per group) as initiation of lung lesions, and surviving mice were killed at 18
      weeks. In the second experiment, mice were treated as above for 4 weeks and
      killed at 6, 12, or 18 weeks (n = 3 per group). Lung lobes were subjected to
      histopathological, immunohistochemical, immunoblotting, and ultrastructural
      analyses. In the case of treatment for 2, 4, and 8 weeks, incidences of lung
      squamous cell carcinoma were 25, 54, and 71%, respectively. Cytokeratin 5/6 and
      epidermal growth factor receptor were clearly expressed in dysplasia and squamous
      cell carcinoma. Desmosomes and tonofilaments developed in the squamous cell
      carcinoma. Considering the carcinogenesis model, we conclude that 2 or 4 weeks of
      N-nitroso-tris-chloroethylurea treatment may be suitable for investigating new
      chemicals for promotional or suppressive effects on lung squamous cell carcinoma.

PMID- 24106884
TI  - Clinical characteristics in schizophrenia patients with or without suicide
      attempts and non-suicidal self-harm--a cross-sectional study.
AB  - BACKGROUND: To investigate whether schizophrenia patients with both suicide
      attempts and non-suicidal self-harm have earlier age of onset of psychotic and
      depressive symptoms and higher levels of clinical symptoms compared to patients
      with only suicide attempts or without suicide attempt. METHODS: Using a cross
      sectional design, 251 patients (18-61 years old, 58% men) with schizophrenia
      treated at hospitals in Oslo and Innlandet Hospital Trust, Norway, were assessed
      with a comprehensive clinical research protocol and divided into three groups
      based on their history of suicide attempts and non-suicidal self-harm. RESULTS:
      Suicide attempts were present in 88 patients (35%); 52 had suicide attempts only
      (29%) and 36 had both suicide attempts and non-suicidal self-harm (14%). When
      compared with nonattempters and those with suicide attempts without non-suicidal
      self-harm, patients with both suicide attempts and non-suicidal self-harm were
      more frequently women, younger at the onset of psychotic symptoms, had longer
      duration of untreated psychosis, and had higher levels of current
      impulsivity/aggression and depression. Patients with both suicide attempts and
      non-suicidal self-harm were more likely to repeat suicide attempts than patients
      with suicide attempts only. CONCLUSIONS: Patients with both suicide attempts and
      non-suicidal self-harm had different illness history and clinical characteristics
      compared to patients with only suicide attempts or patients without suicidal
      behavior. Our study suggests that patients with both suicide attempts and non
      suicidal self-harm represent a distinct subgroup among patients with
      schizophrenia and suicidal behavior with their early onset of psychotic symptoms,
      high rate of repeated suicidal behavior and significant treatment delay.

PMID- 24106885
TI  - Intimate partner violence against women in the Erbil city of the Kurdistan
      region, Iraq.
AB  - BACKGROUND: Violence against women is a worldwide problem and serious human
      rights abuse that occurs among all social, cultural, economic and religious
      groups. There is a paucity of research on intimate partner violence against women
      in Iraq, particularly in the Kurdistan region. This study assessed the prevalence
      of emotional, physical and sexual intimate partner violence against women and the
      impact of physical violence in Erbil, the main city of the Iraqi Kurdistan
      region. METHODS: A cross-sectional study was carried out on a convenience sample
      of 800 Kurdish ever married women. Women (aged 16 to 65 years) attending two
      public hospitals in Erbil city for reproductive health problems were included in
      the study. The study was conducted between 1st of October 2009 and 30th of March
      2011. Each woman was seen only once. Intimate partner violence was assessed by
      administering a modified version of the World Health Organization's domestic
      violence questionnaire through direct interview by a female doctor. Prevalence of
      intimate partner violence was assessed by timing (lifetime or past year),
      frequency (once, 2-5 times, > 5 times), and type (emotional, physical, and sexual
      violence). Descriptive statistical analysis was conducted with calculation of
      frequencies and percentages of women who reported different types, severities and
      impact of intimate partner violence. RESULTS: The prevalence of the overall
      lifetime and the overall past year intimate partner violence against women was
      58.6% and 45.3%, respectively. The proportions of women experienced at least one
      form of lifetime intimate partner violence were: 52.6% for emotional abuse; 38.9%
      for physical violence; and 21.1% for sexual violence, while 43.3%, 15.1%, and
      12.1% of women experienced at least one form of past year emotional, physical and
      sexual violence, respectively. Among those with lifetime physical violence, 11.6%
      were subjected to more serious injuries like stab wound, broken teeth or broken
      bones. CONCLUSIONS: There is a high prevalence of intimate partner violence, in
      particular emotional abuse behavior, against the women attending hospitals in
      Erbil. Physical violence is also a significant problem particularly in terms of
      its consequences.

PMID- 24106886
TI  - Why receptor reserve matters for neurokinin1 (NK1) receptor antagonists.
AB  - The difference in location between the receptor occupancy curve of an agonist and
      its functional response has been described as receptor reserve. This "reserve"
      for a specific receptor has been found to differ from tissue to tissue and
      between agonists acting on the same tissue. Recently, two structurally different
      neurokinin 1 (NK1) receptor antagonists were taken into human and both were
      tested as antidepressants and for insomnia. Vestipitant and Casopitant both have
      high affinity for the human NK1 receptor (pKi = 9.4 and 10.2, respectively). In
      human, at the chosen clinical doses, receptor occupancy was measured in the
      frontal cortex, at 24 hours post administration, as ~90% for vestipitant (15 mg)
      and ~100% for casopitant (30 mg). In patients with moderate to severe major
      depression, vestipitant given at 15 mg for 8 weeks showed no statistical
      significant benefit as measured by change in baseline in HAM-D total score;
      whereas casopitant at 80 mg achieved statistically significant improvement versus
      placebo at week 8 (LOCF HAMD17 = -2.7, p = 0.023). A lower dose of 30 mg showed a
      clear but not significant separation from placebo. However, in acute studies in
      insomnia, both vestipitant and casopitant at 15 mg and 30 mg, respectively,
      significantly reduced latency to persistent sleep, wakenings after sleep onset
      and increased total sleep time by similar amounts. These clinical results suggest
      that for major depression the receptor occupancy of an NK1 antagonist needs to be
      very high (almost 100%), whereas, for insomnia a lower occupation is sufficient
      to give clinical effect.

PMID- 24106887
TI  - Cytokine profiles linked to fatal outcome in infective prosthetic valve
      endocarditis.
AB  - Infective endocarditis is a disease normally of bacterial cause which affects the
      endocardic tissue, specifically the valves (native or prosthetic). It is a
      serious illness and mortality rates remain high, ranging between 20% and 40%.
      Previous reports have evidenced the potential role of cytokines in the diagnosis
      of this disease, but no information is available on their relationship with
      outcome. We recruited 26 consecutive patients with late prosthetic valve
      endocarditis requiring surgical treatment according to Duke criteria. Eight
      cytokines were measured in plasma in the first 24 h following diagnosis by using
      a Bio-Rad multiplex assay. Levels of IL-6, IL-8 and interferon gamma (IFN-gamma)
      were higher in non survivors. Receiver operating characteristic curve analysis
      evidenced that IL-6, IL-8 and IFN-gamma behaved as good diagnostic tests for
      identifying those patients with fatal outcome (area under the curve, CI 95%, p):
      IL-6: [0.81 (0.61-1.00) 0.012]; IL-8 [0.76 (0.56-0.96) 0.035]; IFN-gamma [0.79
      (0.59-0.99) 0.021]. Levels of IL-6, IL-8 and IFN-gamma correlated positively
      between them, indicating that they are produced as consequence of a simultaneous
      response to the infection. Our findings support the participation of IL-6, IL-8
      and IFN-gamma in the events linked to fatal outcome in infective prosthetic valve
      endocarditis.

PMID- 24106888
TI  - Extensive changes in innate immune gene expression in obese Gottingen minipigs do
      not lead to changes in concentrations of circulating cytokines and acute phase
      proteins.
AB  - The usefulness of Gottingen minipigs as models for obesity and obesity-related
      pathologies is well established. The low-grade inflammation associated with
      obesity involves a range of innate immune factors; however, to our knowledge, the
      impact of obesity on innate immune factor expression has not been studied in
      Gottingen minipigs. Therefore, we studied the expression of innate immune genes
      in liver and adipose tissues as well as serum concentrations of cytokines and
      acute phase proteins in obese vs. lean Gottingen minipigs. In the liver, of 35
      investigated genes, the expression of nine was significantly different in obese
      pigs (three up-regulated, six down-regulated). Of 33 genes in adipose tissues,
      obesity was associated with changed expression of 12 genes in the visceral
      adipose tissue (VAT) (three up-regulated), 11 in the abdominal retroperitoneal
      adipose tissue (RPAT) (seven of these up-regulated) and eight in the subcutaneous
      adipose tissue (SAT) from the neck (five of which were up-regulated). Obesity
      associated expression changes were observed for three genes in all adipose
      tissues, namely chemokine (C-C motif) ligand 3-like 1 (up-regulated), CD200
      molecule (down-regulated) and interleukin 1 receptor antagonist (up-regulated)
      with interleukin 1 receptor antagonist being the most highly regulated gene in
      both VAT and RPAT. Looking at patterns of expression across the three types of
      adipose tissues, obesity was associated with an increased number of acute phase
      proteins differentially expressed between adipose tissues and a decreased tissue
      specific expression of cytokines and chemokines. In contrast to obese humans, no
      changes in serum concentrations of haptoglobin, C-reactive protein, serum amyloid
      A, tumor necrosis factor-alpha and interleukin 6 were found in obese Gottingen
      minipigs. 

PMID- 24106889
TI  - Nature's inordinate fondness for metabolic enzymes: why metabolic enzyme loci are
      so frequently targets of selection.
AB  - Metabolic enzyme loci were some of the first genes accessible for molecular
      evolution and ecology research. New technologies now make the whole genome,
      transcriptome or proteome readily accessible, allowing unbiased scans for loci
      exhibiting significant differences in allele frequency or expression level and
      associated with phenotypes and/or responses to natural selection. With surprising
      frequency and in many cases in proportions greater than chance relative to other
      genes, glycolysis and TCA cycle enzyme loci appear among the genes with
      significant associations in these studies. Hence, there is an ongoing need to
      understand the basis for fitness effects of metabolic enzyme polymorphisms.
      Allele-specific effects on the binding affinity and catalytic rate of individual
      enzymes are well known, but often of uncertain significance because metabolic
      control theory and in vivo studies indicate that many individual metabolic
      enzymes do not affect pathway flux rate. I review research, so far little used in
      evolutionary biology, showing that metabolic enzyme substrates affect signalling
      pathways that regulate cell and organismal biology, and that these enzymes have
      moonlighting functions. To date there is little knowledge of how alleles in
      natural populations affect these phenotypes. I discuss an example in which
      alleles of a TCA enzyme locus associate with differences in a signalling pathway
      and development, organismal performance, and ecological dynamics. Ultimately,
      understanding how metabolic enzyme polymorphisms map to phenotypes and fitness
      remains a compelling and ongoing need for gaining robust knowledge of ecological
      and evolutionary processes. 

PMID- 24106890
TI  - Preparation and characterization of novel polytitanium tetrachloride coagulant
      for water purification.
AB  - Polymeric metal coagulants are increasingly being used to improve coagulation
      efficiency, yet the research on the development of titanium and particularly
      polytitanium salts remains limited. This study is the first attempt in the
      synthesis, characterization, and application of polytitanium salts as coagulants.
      Polytitanium tetrachloride (PTC) solutions with different basicity values B
      (OH/Ti molar ratio) were prepared using a slow alkaline titration method. Jar
      tests were conducted to assess coagulation performance using both synthetic and
      real raw water samples, and the floc characteristics were monitored online using
      a laser diffraction particle size analyzer. Electrospray ionization time-of
      flight mass spectrometry (ESI-TOF-MS) was utilized to identify various Ti
      species, with the results providing strong evidence of the presence of various
      hydrolyzed Ti species in the titanium aqueous phase. Compared to titanium
      tetrachloride (TiCl4), higher or comparable turbidity and organic matter removal
      efficiency could be achieved by PTC with improved floc characteristics in terms
      of size, growth rate, and structure. Besides, the water pH after PTC coagulation
      was significantly improved toward neutral pH. This study indicates that PTC is an
      effective and promising coagulant for water purification. Besides, the PTC
      flocculated sludge was able to recycle and produce functional TiO2 photocatalyst.

PMID- 24106891
TI  - A retrospective analysis of the costs and management of genital warts in Italy.
AB  - BACKGROUND: In Italy the prevalence of genital warts in women (15-64 years) is
      approximately 0.6% with an incidence of 0.4% per year. Treatments for GW are
      usually long, with moderate success and high costs. The aim of the study was to
      evaluate the diagnostic-therapeutic pathway, duration and setting of treatment,
      costs of episodes of condyloma in a population attending a regional STI clinic in
      Piedmont. METHODS: This was a retrospective observational study conducted using
      medical records of outpatients who first visited the STI Clinic of San Lazzaro
      Dermatological Hospital in 2008. The patients' medical histories were analysed
      for episodes that occurred and were cleared in 18 months following the initial
      visit. Data on screening methods for STIs, type of diagnosis for condyloma,
      treatment type, treatment setting, and anatomic lesion site were obtained from
      medical records. The costs were calculated for each episode. RESULTS: A total of
      450 episodes were analysed (297 men,153 women). The most frequently affected
      anatomic site was the genital area (74%) in both genders. With regard to
      treatment setting, 78.44% of patients received outpatient treatment at the STI
      clinic, 4% were treated at home, and 0.22% were hospitalised; 11.11% were treated
      in multiple settings. The mean number of treatments per episode was 2.03;
      although many patients received only 1 treatment (n = 207, 46%), exspecially
      cryotherapy or diathermy coagulation (64.73% versus 28.02% of episodes,
      respectively). The mean episode duration was 80.74 days. The mean cost (in 2011
      euros) for an episode was ?158.46 +/- 257.77; the mean costs were ?79.13 +/-
      57.40 for diagnosis and ?79.33 +/- 233.60 for treatment. The mean cost for
      treatment in a STI-Clinic setting was ?111.39 +/- 76.72, that for home treatment
      was ?160.88 +/- 95.69, and that for hospital care was ?2825.94. CONCLUSIONS: The
      treatment of and associated costs for genital warts are significant. Several
      factors affect the cost, and internal STI clinic protocols, such as the 6 month
      window used to consider a recurrence or new diagnosis, create bias. Nonetheless,
      our findings how costs similar to those reported in the international literature
      and should be considered when deciding on which HPV vaccination programs should
      be provided by the public health system.

PMID- 24106893
TI  - Lymph node ratio can further stratify prognosis in subpopulations of breast
      cancer patients with axillary nodal metastases.
AB  - Breast cancer (BC) is the most common cancer in women worldwide and affects one
      in eight women in the UK at some point in their lifetime. Advances in treatment
      have led to greatly improved survival rates. Management of axillary lymph node
      (LN) metastases has been a controversial but evolving area of BC therapy.
      Positive LN status is of vital importance in determining long-term outcomes.
      Recent studies have shown that it is not only the absolute number of involved
      LNs, but also the ratio of metastatic to examined LNs (or LN ratio [LNR]) that
      confers prognostic information. In the evaluated article, a population-wide study
      was performed to elucidate the influence of LNR on mortality risk in Dutch BC
      patients. LNR was an independent prognostic factor, but was not better than
      current tumor, node, metastasis pathological nodal staging. It was, however, able
      to discriminate subpopulations within pathological nodal categories. In this
      article we examine the use of LNR in BC.

PMID- 24106894
TI  - American Society of Clinical Oncology highlights 2013: breast cancer and
      gynecological malignancies.
AB  - The American Society of Clinical Oncology 2013 Annual Meeting took place from May
      31 until June 4 2013 in Chicago (IL, USA). Highlights within the area of
      gynecological oncology and breast cancer included two studies in cervical cancer
      addressing screening as well as treatment of advanced disease. In breast cancer,
      the presented studies covered a wide range of topics from local therapy to
      targeted therapy in the advanced setting. They were not practice changing but
      rather for the most part confirmatory of earlier findings. Last but not least, a
      positive Phase III study, BOLERO III, proved the hypothesis that trastuzumab
      resistance can be overcome by intracellular signal transduction using the mTOR
      inhibitor everolimus. 

PMID- 24106895
TI  - A case of skeletal and bone marrow metastases from breast cancer treated with
      eribulin mesylate.
AB  - AIM: We report our experience with eribulin mesylate in a pancytopenic heavily
      pretreated patient with multiple bone metastases and bone marrow infiltration
      from breast cancer. METHODS: Eribulin mesylate was given at 1.4 mg/m(2) on day 1
      and 8 every 3 weeks for a total of 11 courses. RESULTS: After seven cycles,
      evaluation with a bone marrow biopsy showed a large decrease of neoplastic
      involvement with substitution of osteolitic lesions for the osteoaddensant type.
      No unexpected acute toxicity was observed. CONCLUSION: To our knowledge, this
      represents the first report of bone marrow metastases from breast cancer treated
      with eribulin mesylate that obtained an improvement of hematopoietic values with
      an acceptable profile of tolerability and good compliance for the subject.

PMID- 24106896
TI  - Palonosetron plus dexamethasone in highly emetogenic chemotherapy: pooled data
      from two Phase III trials.
AB  - AIM: Data from two randomized trials were pooled to further characterize the
      effectiveness of palonosetron combined with dexamethasone in the setting of
      highly emetogenic chemotherapy. PATIENTS & METHODS: The analysis included 1411
      patients who were randomized to receive palonosetron or ondansetron/granisetron
      intravenously on day 1 plus either 1-day or 3-day dexamethasone dosing. The
      primary end point was complete response (no vomiting and no rescue antiemetics
      over days 1-5) in cycle one. Data across the studies were analyzed by the Mantel
      Haenszel method. RESULTS: The vast majority of patients received either cisplatin
      (62%) or anthracycline plus cyclophosphamide (34%). The palonosetron regimen
      provided a 12 percentage-point improvement in the rate of overall complete
      response compared with the control regimen (49.2 vs 37.3%; odds ratio: 1.65; 95%
      CI: 1.33-2.04; p < 0.0001). The frequency of no delayed nausea at all daily
      periods was consistently higher in the palonosetron group. CONCLUSION: The
      current analysis confirmed that palonosetron plus dexamethasone improved control
      of highly emetogenic chemotherapy-induced nausea and vomiting throughout 5 days
      postchemotherapy to a significantly greater extent than the combination including
      older 5-HT3 antagonists.

PMID- 24106897
TI  - Cetuximab in combination with chemoradiation after induction chemotherapy of
      locoregionally advanced nasopharyngeal carcinoma: preliminary results.
AB  - AIM: This article aimed to determine treatment compliance, acute toxicities and
      the short-term curative effects of combining cetuximab with chemoradiation
      following induction chemotherapy of locoregionally advanced nasopharyngeal
      carcinoma (NPC). MATERIALS & METHODS: A total of 21 patients with locoregionally
      advanced NPC were scheduled to receive one cycle of induction chemotherapy
      followed by intensity-modulated radiotherapy, weekly administration of cetuximab
      and concurrent chemotherapy (at least two cycles with a limit of six). RESULTS:
      All 21 patients completed the planned radiotherapy, 14 patients (67%) without
      treatment breaks, and 20 patients (95.2%) completed the planned cetuximab
      therapy. Grade 4 toxicities included leukopenia (seven patients; 33.4%),
      neutropenia (three patients; 14.3%), thrombocytopenia (one patient; 4.8%) and
      acneiform rash (one patient; 4.8%). Over a median follow-up period of 13 months
      (range: 3-23 months), the local, regional and distant control rates were 100, 100
      and 95.2%, respectively. CONCLUSION: Cetuximab in combination with intensity
      modulated radiotherapy and chemoradiation is a feasible strategy against
      locoregionally advanced NPC. Preliminary survival data are encouraging compared
      with historic data.

PMID- 24106898
TI  - Prognostic analysis of adjuvant chemotherapy in patients with nasopharyngeal
      carcinoma.
AB  - BACKGROUND: Concurrent chemoradiation has become the standard of treatment in
      locally advanced nasopharyngeal carcinoma. However, the exact magnitude of the
      benefits of adjuvant chemotherapy is still unclear. MATERIALS & METHODS: This is
      a retrospective assessment of 181 patients with newly diagnosed, locally advanced
      nasopharygeal carcinoma who received concurrent chemoradiation followed by
      adjuvant chemotherapy with cisplatin plus fluorouracil in one institution between
      2004 and 2010. RESULTS: The median follow-up period was 40 months (range: 2.1
      96.6 months). The estimated 5-year survival rate of patients with and without
      adjuvant chemotherapy were 83.6 and 66.7%, respectively (p = 0.027). Patients
      receiving two to three cycles of adjuvant chemotherapy had improved outcomes
      compared with those without adjuvant chemotherapy or who had received one cycle.
      Multivariate analysis showed that both advanced stage and suboptimal treatment of
      adjuvant chemotherapy were adverse risk factors in terms of overall survival and
      disease-specific survival. CONCLUSION: Adjuvant chemotherapy with two to three
      cycles of cisplatin plus fluorouracil improved the survival of nasopharyngeal
      carcinoma patients.

PMID- 24106899
TI  - TOP2A protein by quantitative immunofluorescence as a predictor of response to
      epirubicin in the neoadjuvant treatment of breast cancer.
AB  - AIM: Anthracyclines are commonly used in breast cancer, although they lack
      validated predictive biomarkers. We explored the interaction between TOP2A
      protein by quantitative immunofluorescence (QIF) and anthracycline sensitivity.
      PATIENTS & METHODS: Patients with estrogen receptor-negative breast cancer
      received neoadjuvant epirubicin. Pretreatment biopsies were analyzed using
      AQUA((r)). Total, cytoplasmic (C) and nuclear (N) TOP2A protein concentrations
      were expressed as QIF scores and compared with pathologic complete response
      (pCR), TOP2A by immunohistochemistry, TOP2A mRNA, TOP2A and HER2 gene status, and
      Ki-67 level. RESULTS: In total, 76 cases were assessable. C, N, and total scores
      did not correlate with pCR, or other markers. The N:C ratio differed
      significantly by HER2 status. No pCRs occurred in patients in the lowest N:C
      quartile. CONCLUSION: Although no relevant correlation between TOP2A QIF scores
      and pCR was found, N:C ratio may have a negative predictive role, and may merit
      further exploration in a multifactorial predictive model that includes tumor and
      host factors.

PMID- 24106900
TI  - The advantage of circulating tumor cells over serum carcinoembryonic antigen for
      predicting treatment responses in rectal cancer.
AB  - AIM: The objective of this study was to investigate the clinical significance of
      circulating tumor cells (CTCs) on the evaluation and prediction of treatment
      responses in rectal cancer patients compared with serum carcinoembryonic antigen
      (CEA). MATERIALS & METHODS: Both CTCs and CEA levels of 103 rectal cancer
      patients (66 with stage II-III and 37 with recurrence or metastasis) were
      analyzed before and after chemoradiotherapy. CTCs were detected using EpCAM
      magnetic bead-based enrichment combined with cytometric identification. RESULTS:
      CTCs were detected in all patients while no tumor cells were found in healthy
      controls. CTC levels in metastatic patients were significantly higher than those
      with recurrence or stage II-III rectal cancer. There is a close relationship
      between CTC levels and treatment outcomes but serum CEA did not have any
      correlation. CONCLUSION: CTCs are promising markers for the evaluation and
      prediction of treatment responses in rectal cancer patients, superior to the
      conventional tumor marker CEA.

PMID- 24106901
TI  - Endoscopic molecular imaging of cancer.
AB  - White light endoscopy has proven to be a very powerful tool in oncology. There is
      still, however, a need for better endoscopic techniques to overcome the current
      limitations of white light optics. New technologies that allow higher
      sensitivity, improved microanatomy and molecular characterization have been
      available for in vitro microscopy and are now being translated into in vivo
      endoscopy. Endoscopic molecular imaging is still in its infancy but holds the
      promise for enhancing sensitivity for early lesions, thus allowing earlier
      diagnosis and enabling early image-guided endoscopic intervention. A key feature
      of endoscopic molecular imaging is its increased sensitivity and specificity,
      which will be illustrated in this article, as well as describing perspectives on
      its future use in oncologic surgery. 

PMID- 24106902
TI  - Pigmented villonodular synovitis: current concepts about diagnosis and
      management.
AB  - At present, the treatment strategies in patients with localized and diffuse forms
      of pigmented villonodular synovitis have more or less been standardized. However,
      these strategies are not optimal because high recurrence rates persist and
      studies with a sufficient level of evidence are lacking. This systematic review
      article describes all known treatment options for intra-articular pigmented
      villonodular synovitis and their clinical results. Based on this research, we
      provide guidelines to support physicians in making the optimal treatment
      decisions. Given the rarity of the disease, randomized studies are not to be
      expected, but an international registry through existing networks would offer the
      benefit of getting a better insight into the outcome of this disease. Therefore,
      we propose a basic set of data to be investigated and ideally to be reported on
      in such a registry. 

PMID- 24106903
TI  - Systemic therapies in hepatocellular carcinoma: present and future.
AB  - Hepatocellular carcinoma (HCC) is now the third leading cause of cancer
      deathsworldwide and is generally presented at an advanced stage, limiting
      patients' quality of life. The conventional cytotoxic systemic therapy has proved
      to be ineffective in HCC, since its induction several decades ago. Today it is
      possible to use our knowledge of molecular hepatocarcinogenesis to provide a
      targeted therapy. Sorafenib has demonstrated large improvements in overall
      survival in HCC. This review describes the molecular mechanisms and potential
      therapeutic targets, focusing on sorafenib, sunitinib, tivantinib, antiangiogenic
      agents, and current and future immunotherapies. Thus, it will be necessary in the
      future to classify HCCs into subgroups according to their genomic and proteomic
      profiling. The identification of key molecules/receptors/signaling pathways and
      the assessment of their relevance as potential targets will be the main future
      challenge potentially influencing response to therapy. Defining molecular
      targeted agents that are effective for a specific HCC subgroup will hopefully
      lead to personalized therapy. 

PMID- 24106904
TI  - Signaling pathways in lymphoma: pathogenesis and therapeutic targets.
AB  - Lymphoma is the fifth most common cancer in the USA. Most lymphomas are
      classified as non-Hodgkin's lymphoma, and nearly 95% of these cancers are of B
      cell origin. B-cell receptor (BCR) surface expression and BCR functional
      signaling are critical for survival and proliferation of both healthy B cells, as
      well as most B-lymphoma cells. Agents that inhibit various components of the BCR
      signaling pathway, as well as parallel signaling pathways, are currently in
      clinical trials for the treatment of various lymphoma subtypes, including those
      targeting isoforms of PI3K, mTOR and BTK. In this review, we describe the
      signaling pathways in healthy mature B cells, the aberrant signaling in
      lymphomatous B cells and the rationale for clinical trials of agents targeting
      these pathways as well as the results of clinical trials to date. We propose that
      the entry into a kinase inhibitor era of lymphoma therapy will be as
      transformative for our patients as the advent of the antibody or chemotherapy era
      before it. 

PMID- 24106905
TI  - HSF1-mediated regulation of tumor cell apoptosis: a novel target for cancer
      therapeutics.
AB  - Programmed cell death/apoptosis is a genetically conserved phenomenon involved in
      many biological processes including reconstruction of multicellular organisms and
      elimination of old or damaged cells. It is regulated by the
      activation/deactivation of PKC in response to exogenous and endogenous stimuli.
      PKC is activated under stress by a series of downstream signaling cascades, which
      ultimately induce HSF1 activation, which results in overexpression of heat shock
      proteins. Overexpression of heat shock proteins interferes in the apoptotic
      pathway, while their blocking results in apoptosis. Therefore, HSF1 could be a
      novel therapeutic target against a variety of tumors. Several pharmacological
      inhibitors of PKC have been demonstrated to exert inhibitory effects on the
      activation of HSF1 and, therefore, induce apoptosis in tumor cells. However,
      studies regarding the role of pharmacological inhibitors in the regulation of
      apoptosis and possible anti-tumor therapeutic intervention are still unknown or
      in their infancy. Therefore, an attempt has been made to delineate the precise
      role of HSF1 in the regulation of apoptosis and its prospects in cancer
      therapeutics. 

PMID- 24106906
TI  - Novel oncoprotein EPS8: a new target for anticancer therapy.
AB  - EPS8 was first identified as a tyrosine kinase substrate, that plays a role in
      EGFR-mediated mitogenic signaling. Recent research has shown that EPS8 is
      overexpressed in most types of cancer, for example breast cancer, colon cancer,
      cervical cancer and even hematologic malignancies. EPS8 is involved in many
      signaling pathways related to tumorigenesis, proliferation, migration and
      metastasis, and is a biomarker for poor prognosis of cancer patients. This review
      aims to provide a comprehensive picture of the role of EPS8 in cellular processes
      and its significance to tumorigenesis. Furthermore, this review focuses on the
      potential role of EPS8 as a therapeutic cancer target. 

PMID- 24106908
TI  - Challenges and prospects in the telemetry of insects.
AB  - Radio telemetry has been widely used to study the space use and movement
      behaviour of vertebrates, but transmitter sizes have only recently become small
      enough to allow tracking of insects under natural field conditions. Here, we
      review the available literature on insect telemetry using active (battery
      powered) radio transmitters and compare this technology to harmonic radar and
      radio frequency identification (RFID) which use passive tags (i.e. without a
      battery). The first radio telemetry studies with insects were published in the
      late 1980s, and subsequent studies have addressed aspects of insect ecology,
      behaviour and evolution. Most insect telemetry studies have focused on habitat
      use and movement, including quantification of movement paths, home range sizes,
      habitat selection, and movement distances. Fewer studies have addressed foraging
      behaviour, activity patterns, migratory strategies, or evolutionary aspects. The
      majority of radio telemetry studies have been conducted outside the tropics,
      usually with beetles (Coleoptera) and crickets (Orthoptera), but bees
      (Hymenoptera), dobsonflies (Megaloptera), and dragonflies (Odonata) have also
      been radio-tracked. In contrast to the active transmitters used in radio
      telemetry, the much lower weight of harmonic radar and RFID tags allows them to
      be used with a broader range of insect taxa. However, the fixed detection zone of
      a stationary radar unit (< 1 km diameter) and the restricted detection distance
      of RFID tags (usually < 1-5 m) constitute major constraints of these technologies
      compared to radio telemetry. Most of the active transmitters in radio telemetry
      have been applied to insects with a body mass exceeding 1 g, but smaller species
      in the range 0.2-0.5 g (e.g. bumblebees and orchid bees) have now also been
      tracked. Current challenges of radio-tracking insects in the field are related to
      the constraints of a small transmitter, including short battery life (7-21 days),
      limited tracking range on the ground (100-500 m), and a transmitter weight that
      sometimes approaches the weight of a given insect (the ratio of tag mass to body
      mass varies from 2 to 100%). The attachment of radio transmitters may constrain
      insect behaviour and incur significant energetic costs, but few studies have
      addressed this in detail. Future radio telemetry studies should address (i) a
      larger number of species from different insect families and functional groups,
      (ii) a better coverage of tropical regions, (iii) intraspecific variability
      between sexes, ages, castes, and individuals, and (iv) a larger tracking range
      via aerial surveys with helicopters and aeroplanes equipped with external
      antennae. Furthermore, field and laboratory studies, including observational and
      experimental approaches as well as theoretical modelling, could help to clarify
      the behavioural and energetic consequences of transmitter attachment. Finally,
      the development of commercially available systems for automated tracking and
      potential future options of insect telemetry from space will provide exciting new
      avenues for quantifying movement and space use of insects from local to global
      spatial scales. 

PMID- 24106909
TI  - Palladium-catalyzed oxidative acetoxylation of benzylic C-H bond using bidentate
      auxiliary.
AB  - Pd(OAc)2-catalyzed oxidative acetoxylation of benzylic C-H bonds utilizing a
      bidentate system has been explored. A variety of picolinoyl- or quinoline-2
      carbonyl-protected toluidine derivatives react with PhI(OAc)2 in the presence of
      Pd(OAc)2 to afford the acetoxylated products in synthetically useful yields. A
      broad of functionalities, such as CH3, F, Cl, Br, I, COCH3, CO2Et, SO2CH3, and
      NO2, were tolerated. This transformation provides easy access to 2
      hydroxymethylaniline derivatives. 

PMID- 24106910
TI  - Professionalism and caring for Medicaid patients--the 5% commitment?

PMID- 24106911
TI  - Microbes in the upper atmosphere and unique opportunities for astrobiology
      research.
AB  - Microbial taxa from every major biological lineage have been detected in Earth's
      upper atmosphere. The goal of this review is to communicate (1) relevant
      astrobiology questions that can be addressed with upper atmosphere microbiology
      studies and (2) available sampling methods for collecting microbes at extreme
      altitudes. Precipitation, mountain stations, airplanes, balloons, rockets, and
      satellites are all feasible routes for conducting aerobiology research. However,
      more efficient air samplers are needed, and contamination is also a pervasive
      problem in the field. Measuring microbial signatures without false positives in
      the upper atmosphere might contribute to sterilization and bioburden reduction
      methods for proposed astrobiology missions. Intriguingly, environmental
      conditions in the upper atmosphere resemble the surface conditions of Mars
      (extreme cold, hypobaria, desiccation, and irradiation). Whether terrestrial
      microbes are active in the upper atmosphere is an area of intense research
      interest. If, in fact, microbial metabolism, growth, or replication is achievable
      independent of Earth's surface, then the search for habitable zones on other
      worlds should be broadened to include atmospheres (e.g., the high-altitude clouds
      of Venus). Furthermore, viable cells in the heavily irradiated upper atmosphere
      of Earth could help identify microbial genes or enzymes that bestow radiation
      resistance. Compelling astrobiology questions on the origin of life (if the
      atmosphere synthesized organic aerosols), evolution (if airborne transport
      influenced microbial mutation rates and speciation), and panspermia (outbound or
      inbound) are also testable in Earth's upper atmosphere.

PMID- 24106912
TI  - The role and prognostic value of apoptosis in colorectal carcinoma.
AB  - BACKGROUND: Alterations to apoptosis are a common occurrence in human tumours.
      The aim of our study was to determine the influence of apoptotic variations on
      the carcinogenesis and prognosis of colorectal carcinomas (CRCs). METHODS: A
      TUNEL assay was performed on archival material from 103 colorectal carcinomas, 26
      adenomas and 20 samples of normal epithelia. RESULTS: The number of apoptotic
      cells was higher in CRCs (1.09 +/- 0.13) than in adenomas (0.38 +/- 0.23, p =
      0.059) and normal epithelium (0.06 +/- 0.04, p = 0.001). In addition, the
      apoptotic index (AI) was greater in metastatic disease (stage IV) than in other
      stages (p = 0.017). No relationship was found between apoptotic rates and age,
      gender or tumour grade. However, patients with tumours that showed higher AI
      values had a significantly lower disease-free survival (DFS) and overall survival
      (OS) than those with tumours that had lower AIs (p = 0.020 and p = 0.027). In a
      multivariate Cox proportional hazards model, AI remained a significant
      independent predictor of survival. CONCLUSIONS: We conclude that disregulated
      apoptosis is an important event during CRC development and progression. Higher
      AIs are associated with more aggressive tumours and a poorer prognosis for
      patients with CRC.

PMID- 24106913
TI  - The effect of SN-6, a novel sodium-calcium exchange inhibitor, on contractility
      and calcium handling in isolated failing rat ventricular myocytes.
AB  - BACKGROUND AND PURPOSE: Specific Na(+) /Ca(2+) exchanger (NCX) inhibition is a
      potential strategy to correct reduced contractility and depleted sarcoplasmic
      reticulum (SR) Ca(2+) content in heart failure (HF). SN-6, a benzyloxyphenyl
      derivative and proposed selective NCX inhibitor, could be used for this purpose.
      This study aimed to evaluate the effects of SN-6 on contractility and Ca(2+)
      handling in normal and failing rat cardiomyocytes. EXPERIMENTAL APPROACH: HF was
      induced in rats by coronary artery ligation. Left ventricular myocytes were
      isolated and superfused with increasing concentrations of SN-6. KEY RESULTS:
      Sarcomere shortening, induced by field-stimulation, was reduced in amplitude with
      increasing concentrations of SN-6 compared with control solution. This effect was
      greater in failing cells. Kinetics of contractility (time to 90% peak and time to
      50% relaxation) were significantly faster. Despite this, intracellular Ca(2+)
      transients demonstrated no change in the peak amplitude at low concentrations of
      SN-6, suggesting that SN-6 may affect myofilament sensitivity to Ca(2+) . Ten
      micro molar SN-6 significantly reduced peak Ca(2+) amplitude by 61.57% and 64.73%
      in normal and failing cells, respectively. Diastolic Ca(2+) was significantly
      increased at 1 MUM SN-6. SR Ca(2+) content, assessed by rapid application of
      caffeine, was reduced in failing cells with 1 MUM SN-6. Peak ICa , measured by
      whole-cell patch clamping, was significantly reduced in normal and failing
      myocytes at 1 MUM SN-6. CONCLUSIONS AND IMPLICATIONS: Our data suggest that SN-6
      is not a selective inhibitor of NCX and impairs contractility and Ca(2+)
      handling. Its use, together with similar putative NCX blockers, in correcting the
      contractile abnormalities of heart failure requires further studies.

PMID- 24106914
TI  - Antifungal activity of hypothemycin against Peronophythora litchii in vitro and
      in vivo.
AB  - The antifungal activity of a natural resorcylic acid lactone, hypothemycin (HPM),
      against Peronophythora litchii in vitro and in vivo was investigated. HPM
      treatment substantially suppressed spore germination of P. litchi, with the
      inhibition rate of 100% when 0.78 MUg/mL HPM was applied. Similarly, mycelial
      growth of P. litchii was efficiently inhibited. Furthermore, HPM caused the
      ultrastructural modifications of P. litchii, including the disruption of the cell
      wall and the endomembrane system, especially the plasma membrane, mitochondria,
      and vacuoles, which led to the destruction of the cellular integrity. Moreover,
      application of HPM significantly reduced decay and suppressed peel browning of
      postharvest litchi fruit inoculated with P. litchii during storage at 28  degrees
      C. Overall, these findings suggested that HPM exhibited excellent antifungal
      activity against P. litchii both in vitro and in vivo, which could be helpful for
      the storage of harvest litchi fruit. 

PMID- 24106915
TI  - In situ fabricated polymer-silver nanocomposite thin film as an inexpensive and
      efficient substrate for surface-enhanced Raman scattering.
AB  - The utility of polymer-metal nanocomposite thin films with in situ generated
      silver nanoparticles as substrates for surface-enhanced Raman scattering (SERS)
      is demonstrated. Thin films of poly(vinyl alcohol) and poly(vinyl butyral-co
      vinyl alcohol-co-vinyl acetate) containing Ag nanoparticles generated in situ
      through thermal annealing and photoirradiation, respectively (Ag-PVA and Ag
      PVVV), are investigated as potential SERS substrates using 4-aminothiophenol and
      rhodamine 6G as probe molecules. The fabrication protocols are extremely simple
      and the materials inexpensive. The Ag-PVA substrate is found to produce Raman
      spectral enhancement factors of ~10(6), whereas Ag-PVVV, a novel nanocomposite
      thin film developed in the present study, provides enhancement factors of ~10(7).
      A unique advantage of these nanocomposite films is demonstrated by fabricating
      them by the in situ process as a thin coating inside glass capillaries and using
      these disposable SERS substrates for the sensitive detection of the probe
      molecules. The thin film substrates prepared on glass plates and capillaries
      facilitate convenient sample preparation for recording the Raman spectra and
      provide strongly enhanced spectra with high reproducibility, allowing picomols of
      the analytes to be detected. These aspects combined with the ease of fabrication
      and low cost of these in situ fabricated nanocomposite thin films make them
      highly attractive SERS substrates.

PMID- 24106916
TI  - Single vehicular delivery of siRNA and small molecules to control stem cell
      differentiation.
AB  - Achieving a controlled and reproducible means to direct stem cell differentiation
      is the single most critical concern scientists have been trying to address since
      the discovery of stem cells. In this regard, the use of small molecules and RNA
      interference offers unique advantages by targeting different cellular mechanisms.
      Our cyclodextrin-modified dendritic polyamine construct (termed DexAM) combines
      the unique properties of two distinct chemical moieties in a single delivery
      vehicle. DexAM is a single vehicle that not only solubilizes hydrophobic small
      molecules in physiological solutions but also forms complexes with siRNA
      molecules, making it an attractive delivery system for controlling stem cell
      differentiation. Herein, we report the synthesis and application of DexAM to
      simultaneously deliver hydrophobic small molecules and siRNA into neural stem
      cells to significantly enhance their neuronal differentiation. 

PMID- 24106917
TI  - Comparing patient dissatisfaction and rational judgment in intentional medication
      non-adherence versus unintentional non-adherence.
AB  - WHAT IS KNOWN AND OBJECTIVE: Patients' poor adherence to medications is reported
      to be related to the individual patients' beliefs and cognitions and their trust
      of the medical staff. However, the causes of the two forms of non-adherence,
      intentional and unintentional behaviours, have yet to be clarified. This study
      compared psychological latent factors associated with intentional and
      unintentional non-adherence to chronic medication regimens, focusing on the
      potential effects of (i) patients' dissatisfaction with treatment and their
      relationships with the medical staff and (ii) patients' subliminal rational
      thinking processes, which weighed the positive values such as their expectations
      of benefits from treatment against negative values such as their dissatisfaction.
      METHODS: Two cross-sectional surveys were undertaken of patients given
      medications for chronic diseases, using a questionnaire developed and validated
      in this study. One survey was undertaken in three hospitals and the other survey,
      online throughout Japan. We scored the individual latent factors using the
      questionnaire and calculated the differential score between two negatively
      correlated latent factors to quantify patients' subliminal rational thinking
      process. We compared the adjusted odds ratio (OR) of latent factors between
      intentional and unintentional non-adherence to medication in both surveys.
      RESULTS AND DISCUSSION: Of the eligible subjects, 149 hospitalized patients and
      524 survey participants completed the questionnaire. Intentional non-adherence
      was associated with patient dissatisfaction with treatment including
      interpersonal relationships with medical staff in both hospitalized patients and
      online survey participants (95% confidence interval of adjusted OR for
      Dissatisfaction, 1.20-16.26 in the hospital-based survey and 1.33-3.45 in the
      online survey). In both surveys, intentional non-adherence was significantly
      associated with the differential score between two negatively correlated latent
      factors, Willingness and Dissatisfaction (P = 0.02 in the hospital-based survey
      and P < 0.001 in the online survey). However, these associations were not evident
      in unintentionally non-adherent patients. WHAT IS NEW AND CONCLUSIONS: Patients'
      dissatisfaction and their resulting rational judgments are unique, consistent
      determinants of intentional non-adherence to medications, but not of
      unintentional non-adherence.

PMID- 24106918
TI  - Cognitive Bias Modification (CBM) of obsessive compulsive beliefs.
AB  - BACKGROUND: Cognitive bias modification (CBM) protocols have been developed to
      help establish the causal role of biased cognitive processing in maintaining
      psychopathology and have demonstrated therapeutic benefits in a range of
      disorders. The current study evaluated a cognitive bias modification training
      paradigm designed to target interpretation biases (CBM-I) associated with
      obsessive compulsive disorder (OCD). METHODS: We evaluated the impact of CBM-I on
      measures of interpretation bias, distress, and on responses to three OC stressor
      tasks designed to tap the core belief domains of Importance of Thoughts/Control,
      Perfectionism/Intolerance of Uncertainty, and Contamination/Estimation of Threat
      in a selected sample of community members reporting obsessive compulsive (OC)
      symptoms (N = 89). RESULTS: Participants randomly assigned to the Positive
      condition evidenced a change in interpretation bias towards more positive and
      less negative OC-relevant interpretations following CBM-I compared to
      participants assigned to the Control condition. Importantly, a positivity bias
      was not observed for foil scenarios unrelated to the core OC belief domains.
      Further, participants in the Positive condition reported less distress and urge
      to neutralize following an OC stressor task designed to tap Importance of
      Thoughts/Control. No significant difference emerged on the indices of behavioural
      response to the OC stressor tasks. Severity of OC symptoms did not moderate the
      effects of positive CBM-I training. CONCLUSIONS: CBM-I appears effective in
      selectively targeting OC beliefs. Results need to be replicated in clinical
      samples in order for potential therapeutic benefit to be demonstrated.

PMID- 24106919
TI  - Role of macrophage infiltration in successful repigmentation in a new periphery
      spreading vitiligo lesion in a male Japanese patient.
AB  - Vitiligo is an acquired disorder in which depigmented macules result from mostly
      autoimmune loss of melanocytes. The initiating process in vitiligo has still been
      uncertain. Here, we report the case of a 19-year-old man with
      undetermined/unclassified vitiligo with a new periphery-spreading vitiligo lesion
      on the right dorsal hand after rigorous sun exposure. Histopathological
      evaluation showed noticeable infiltration of CD68(+) macrophages, moderate
      infiltration of CD3(+) T cells, little infiltration of CD8(+) T cells and
      CD11c(+) myeloid dendritic cells, HMB45/CD11c double-positive cells, and Melan
      A/MART1(+) deposits in the dermis. We surmised that melanocyte-derived deposits
      were mostly phagocytosed by CD68(+) macrophages and were faintly phagocytosed by
      CD11c(+) myeloid dendritic cells, referring distribution of CD68(+) mononuclear
      cells and melanocyte biomarkers. Complete repigmentation was achieved following
      topical application of hydrocortisone butyrate propionate 0.1% ointment. We
      summarize that prompt clearance of debris by macrophages would be essential to an
      excellent prognosis of complete repigmentation. 

PMID- 24106922
TI  - Cesarean delivery under spinal anesthesia is associated with decreases in
      cerebral oxygen saturation as assessed by NIRS: an observational study.
AB  - OBJECTIVES: To investigate the effect of spinal anesthesia on cerebral rSO2
      during elective cesarean delivery (CD). METHODS: Thirty-four women scheduled for
      elective CD under spinal anesthesia were recruited. In the operating room rSO2 of
      the left and right frontal area and right thigh was recorded using three
      disposable sensors. A combination of 1.8-2.0 ml of 0.75% ropivacaine plus 10 MUg
      of fentanyl were injected intrathecally. Systolic and diastolic blood pressure,
      heart rate, SpO2 as well as rSO2 of the left and right forehead areas and right
      thigh were recorded before, 5, 10, and 25 to 50 minutes after spinal injection,
      after uterine incision and placenta delivery, and analyzed with ANOVA repeated
      measures. The study was approved by the Aretaieio Hospital Institutional Review
      Board and registered with ClinicalTrials.gov (ID: NCT01669135). RESULTS: The rSO2
      left and right frontal area values decreased significantly from baseline
      (p=0.0001 and p=0.0001 respectively), with most remarkable decreases 5 and 10
      minutes after spinal injection, from 65 (SD 8.7)% to 56 (SD 9.3)% and 56 (SD
      9.5)% (p=0.0001 and p=0.0001) for the left and from 63 (SD 7.7)% to 55 (SD 9.3)%
      and 56 (SD 8.9)% (p=0,0001 and p=0.0001) for the right frontal area respectively.
      The rSO2 right thigh values increased significantly during the study period
      (p=0.0001). KEY LIMITATIONS: Contribution of extracranial circulation to the
      rSO2, lack of PaCO2 and cardiac output measurements. CONCLUSIONS: Women
      undergoing CD under spinal anesthesia may present decreases in cerebral rSO2. The
      clinical impact of these results remains to be determined.

PMID- 24106925
TI  - Controlling FIB-SBEM slice thickness by monitoring the transmitted ion beam.
AB  - Serial block-face electron microscopy with focused ion beam cutting suffers from
      cutting artefacts caused by changes in the relative position of beam and sample,
      which are, for example, inevitable when reconditioning the ion gun. The latter
      has to be done periodically, which limits the continuous stack-acquisition time
      to several days. Here, we describe a method for controlling the ion-beam position
      that is based on detecting that part of the ion beam that passes the sample
      (transmitted beam). We find that the transmitted-beam current decreases
      monotonically as the beam approaches the sample and can be used to determine the
      relative position of beam and sample to an accuracy of around one nanometre. By
      controlling the beam approach using this current as the feedback parameter, it is
      possible to ion-mill consecutive 5 nm slices without detectable variations in
      thickness even in the presence of substantial temperature fluctuations and to
      restart the acquisition of a stack seamlessly. In addition, the use of a silicon
      junction detector instead of the in-column detector is explored. 

PMID- 24106924
TI  - Effect of prucalopride on symptoms of chronic constipation.
AB  - BACKGROUND: Prucalopride is a 5-HT4 receptor agonist with gastrointestinal
      prokinetic activities. This integrated analysis of data from three 12-week,
      double-blind trials evaluated the effect of prucalopride 2 mg q.d. on common
      constipation symptoms in women in whom laxatives had failed to provide adequate
      relief. The effect of prucalopride on bowel function was outside the scope of the
      analysis and has been described elsewhere. METHODS: Women with self-reported
      inadequate relief from laxatives and included in the prucalopride 2 mg or placebo
      arm of the trials were selected for analysis. Symptom severity was determined
      with the Patient Assessment of Constipation Symptoms (PAC-SYM) questionnaire.
      Observed changes from baseline in individual item scores were also evaluated by
      calculating Cohen's D effect sizes using baseline standard deviation (SD) (>0.2
      0.5, >0.5-0.8 and >0.8 for small, moderate and large effects, respectively). KEY
      RESULTS: Data were analyzed for 936 women. The proportion of women with a PAC-SYM
      severity score >2 at baseline was 50.0% for abdominal symptoms, 71.4% for stool
      symptoms, and 15.5% for rectal symptoms. Excluding the women without presence of
      a symptom at baseline from the effect size calculations showed that prucalopride
      2 mg had a large effect (>0.8) on all PAC-SYM items, including abdominal pain,
      abdominal discomfort, bloating, straining, and painful bowel movements. For
      abdominal symptoms and stool symptoms, effect sizes with prucalopride 2 mg were
      1.3-2.3 times larger than those with placebo. CONCLUSIONS & INFERENCES:
      Prucalopride 2 mg q.d. for 12 weeks alleviates common constipation symptoms in
      women in whom laxatives had failed to provide adequate relief.

PMID- 24106923
TI  - Calcium ions and osteoclastogenesis initiate the induction of bone formation by
      coral-derived macroporous constructs.
AB  - Coral-derived calcium carbonate/hydroxyapatite macroporous constructs of the
      genus Goniopora with limited hydrothermal conversion to hydroxyapatite (7% HA/CC)
      initiate the induction of bone formation. Which are the molecular signals that
      initiate pattern formation and the induction of bone formation? To evaluate the
      role of released calcium ions and osteoclastogenesis, 7% HA/CC was pre-loaded
      with either 500 MUg of the calcium channel blocker, verapamil hydrochloride, or
      240 MUg of the osteoclast inhibitor, biphosphonate zoledronate, and implanted in
      the rectus abdominis muscle of six adult Chacma baboons Papio ursinus. Generated
      tissues on days 15, 60 and 90 were analysed by histomorphometry and qRT-PCR. On
      day 15, up-regulation of type IV collagen characterized all the implanted
      constructs correlating with vascular invasion. Zoledronate-treated specimens
      showed an important delay in tissue patterning and morphogenesis with limited
      bone formation. Osteoclastic inhibition yielded minimal, if any, bone formation
      by induction. 7% HA/CC pre-loaded with the Ca(++) channel blocker verapamil
      hydrochloride strongly inhibited the induction of bone formation. Down-regulation
      of bone morphogenetic protein-2 (BMP-2) together with up-regulation of Noggin
      genes correlated with limited bone formation in 7% HA/CC pre-loaded with either
      verapamil or zoledronate, indicating that the induction of bone formation by
      coral-derived macroporous constructs is via the BMPs pathway. The spontaneous
      induction of bone formation is initiated by a local peak of Ca(++) activating
      stem cell differentiation and the induction of bone formation. 

PMID- 24106927
TI  - Magnetic fluid hyperthermia: advances, challenges, and opportunity.
AB  - Though the concepts of magnetic fluid hyperthermia (MFH) were originally proposed
      over 50 years ago, the technique has yet to be successfully translated into
      routine clinical application. Significant challenges must be addressed if the
      field is to progress and realise its potential as an option for treatment of
      diseases such as cancer. These challenges include determining the optimum fields
      and frequencies that maximise the effectiveness of MFH without significant
      detrimental off-target effects on healthy tissue, achieving sufficient
      concentrations of magnetic nanoparticles (MNPs) within the target tumour, and
      developing a better mechanistic understanding of MNP-mediated energy deposition
      and its effects on cells and tissue. On the other hand, emerging experimental
      evidence indicates that local thermal effects indeed occur in the vicinity of
      energy-dissipating MNPs. These findings point to the opportunity of engineering
      MNPs for the selective destruction of cells and/or intracellular structures
      without the need for a macroscopic tissue temperature rise, in what we here call
      magnetically mediated energy delivery (MagMED).

PMID- 24106928
TI  - Selection criteria for selective dorsal rhizotomy in children with spastic
      cerebral palsy: a systematic review of the literature.
AB  - AIM: Information regarding the selection procedure for selective dorsal rhizotomy
      (SDR) in children with spastic cerebral palsy (CP) is scarce. Therefore, the aim
      of this study was to summarize the selection criteria for SDR in children with
      spastic CP. METHOD: A systematic review was carried out using the following
      databases: MEDLINE, CINAHL, EMBASE, PEDro, and the Cochrane Library. Additional
      studies were identified in the reference lists. Search terms included 'selective
      dorsal rhizotomy', 'functional posterior rhizotomy', 'selective posterior
      rhizotomy', and 'cerebral palsy'. Studies were selected if they studied mainly
      children (<18y of age) with spastic CP, if they had an intervention of SDR, if
      they had a detailed description of the selection criteria, and if they were in
      English. The levels of evidence, conduct of studies, and selection criteria for
      SDR were scored. RESULTS: Fifty-two studies were included. Selection criteria
      were reported in 16 International Classification of Functioning, Disability and
      Health model domains including 'body structure and function' (details concerning
      spasticity [94%], other movement abnormalities [62%], and strength [54%]),
      'activity' (gross motor function [27%]), and 'personal and environmental factors'
      (age [44%], diagnosis [50%], motivation [31%], previous surgery [21%], and follow
      up therapy [31%]). Most selection criteria were not based on standardized
      measurements. INTERPRETATION: Selection criteria for SDR vary considerably.
      Future studies should describe clearly the selection procedure. International
      meetings of experts should develop more uniform consensus guidelines, which could
      form the basis for selecting candidates for SDR.

PMID- 24106930
TI  - PEPFAR in transition--implications for HIV care in South Africa.

PMID- 24106931
TI  - Threatened hope--PEPFAR and health in Africa.

PMID- 24106929
TI  - Inhibition of ceramide de novo synthesis reduces liver lipid accumulation in rats
      with nonalcoholic fatty liver disease.
AB  - BACKGROUND & AIMS: Nonalcoholic fatty liver disease (NAFLD) is an insulin
      resistance-related hepatic disorder which can transform to cirrhosis. Insulin
      resistance deregulates hepatic lipid metabolism, leading to accumulation of
      cytotoxic lipids including ceramide and diacylglycerols. Myriocin, obtained from
      fungi traditionally used in Chinese medicine in an effort to attain eternal
      youth, is a potent pharmacological inhibitor of ceramide de novo synthesis. We
      examined whether inhibition of ceramide de novo synthesis with myriocin
      ameliorate hepatic lipid accumulation and reverse NAFLD. METHODS: The experiment
      was carried out on male Wistar rats. The animals were divided into four groups:
      (i) control group, fed standard rodent diet, (ii) group, fed standard diet also
      treated with myriocin for 7 days, (iii) group, fed high-fat diet for 5 weeks,
      (iv) group, fed high-fat diet and treated with myriocin. In liver samples
      sphingolipids: ceramide, sphingosine and sphingosine-1-phosphatate and neutral
      lipids, such as diacylglycerols and triacylglycerols were measured. In peripheral
      blood samples, glucose and insulin levels and aminotransferases activities were
      measured. RESULTS: High-fat diet feeding caused NAFLD, confirmed by histological
      assessment, with increased hepatic lipids accumulation and whole-body insulin
      resistance. After treating with inhibitor of ceramide de novo synthesis, decrease
      in hepatic ceramide and other toxic lipids were noticed. Moreover, histological
      analysis of liver samples revealed that inhibition of ceramide de novo synthesis
      reduced hepatic steatosis. CONCLUSIONS: Inhibition of ceramide de novo synthesis
      reduced hepatic lipid accumulation in rats with NAFLD, this led to amelioration
      of hepatic steatosis.

PMID- 24106932
TI  - Training physicians to manage obesity--back to the drawing board.

PMID- 24106933
TI  - No easy fixes.

PMID- 24106934
TI  - A dimorphic fungus causing disseminated infection in South Africa.
AB  - BACKGROUND: The genus emmonsia contains three species that are associated with
      human disease. Emmonsia crescens and Emmonsia parva are the agents that cause
      adiaspiromycosis, and one human case of Emmonsia pasteuriana infection has been
      described. We report a fungal pathogen within the genus emmonsia that is most
      closely related to E. pasteuriana in human immunodeficiency virus (HIV)-infected
      adults in South Africa. METHODS: Between July 2008 and July 2011, we conducted
      enhanced surveillance to identify the cause of systemic, dimorphic fungal
      infections in patients presenting to Groote Schuur Hospital and other hospitals
      affiliated with the University of Cape Town, Cape Town, South Africa. DNA
      sequencing was used to identify pathogenic fungi. RESULTS: A total of 24 cases of
      dimorphic fungal infection were diagnosed, 13 of which were caused by an emmonsia
      species. All 13 patients were HIV-infected, with a median CD4+ T-cell count of 16
      cells per cubic millimeter (interquartile range, 10 to 44), and all had evidence
      of disseminated fungal disease. Three patients died soon after presentation, but
      the others had a good response to a variety of antifungal agents and
      antiretroviral therapy. Phylogenetic analysis of five genes (LSU, ITS1-2, and the
      genes encoding actin, beta-tubulin, and intein PRP8) revealed that this fungus
      belongs in the genus emmonsia and is most closely related to E. pasteuriana.
      CONCLUSIONS: The findings suggest that these isolates of an emmonsia species
      represent a new species of dimorphic fungus that is pathogenic to humans. The
      species appears to be an important cause of infections in Cape Town.

PMID- 24106935
TI  - High-flow nasal cannulae in very preterm infants after extubation.
AB  - BACKGROUND: The use of high-flow nasal cannulae is an increasingly popular
      alternative to nasal continuous positive airway pressure (CPAP) for noninvasive
      respiratory support of very preterm infants (gestational age, <32 weeks) after
      extubation. However, data on the efficacy or safety of such cannulae in this
      population are lacking. METHODS: In this multicenter, randomized, noninferiority
      trial, we assigned 303 very preterm infants to receive treatment with either high
      flow nasal cannulae (5 to 6 liters per minute) or nasal CPAP (7 cm of water)
      after extubation. The primary outcome was treatment failure within 7 days.
      Noninferiority was determined by calculating the absolute difference in the risk
      of the primary outcome; the margin of noninferiority was 20 percentage points.
      Infants in whom treatment with high-flow nasal cannulae failed could be treated
      with nasal CPAP; infants in whom nasal CPAP failed were reintubated. RESULTS: The
      use of high-flow nasal cannulae was noninferior to the use of nasal CPAP, with
      treatment failure occurring in 52 of 152 infants (34.2%) in the nasal-cannulae
      group and in 39 of 151 infants (25.8%) in the CPAP group (risk difference, 8.4
      percentage points; 95% confidence interval, -1.9 to 18.7). Almost half the
      infants in whom treatment with high-flow nasal cannulae failed were successfully
      treated with CPAP without reintubation. The incidence of nasal trauma was
      significantly lower in the nasal-cannulae group than in the CPAP group (P=0.01),
      but there were no significant differences in rates of serious adverse events or
      other complications. CONCLUSIONS: Although the result for the primary outcome was
      close to the margin of noninferiority, the efficacy of high-flow nasal cannulae
      was similar to that of CPAP as respiratory support for very preterm infants after
      extubation. (Funded by the National Health and Medical Research Council;
      Australian New Zealand Clinical Trials Network number, ACTRN12610000166077.).

PMID- 24106937
TI  - Diagnostic criteria for nonviable pregnancy early in the first trimester.

PMID- 24106938
TI  - Images in clinical medicine. Gingival melanoma.

PMID- 24106936
TI  - Surgical skill and complication rates after bariatric surgery.
AB  - BACKGROUND: Clinical outcomes after many complex surgical procedures vary widely
      across hospitals and surgeons. Although it has been assumed that the proficiency
      of the operating surgeon is an important factor underlying such variation,
      empirical data are lacking on the relationships between technical skill and
      postoperative outcomes. METHODS: We conducted a study involving 20 bariatric
      surgeons in Michigan who participated in a statewide collaborative improvement
      program. Each surgeon submitted a single representative videotape of himself or
      herself performing a laparoscopic gastric bypass. Each videotape was rated in
      various domains of technical skill on a scale of 1 to 5 (with higher scores
      indicating more advanced skill) by at least 10 peer surgeons who were unaware of
      the identity of the operating surgeon. We then assessed relationships between
      these skill ratings and risk-adjusted complication rates, using data from a
      prospective, externally audited, clinical-outcomes registry involving 10,343
      patients. RESULTS: Mean summary ratings of technical skill ranged from 2.6 to 4.8
      across the 20 surgeons. The bottom quartile of surgical skill, as compared with
      the top quartile, was associated with higher complication rates (14.5% vs. 5.2%,
      P<0.001) and higher mortality (0.26% vs. 0.05%, P=0.01). The lowest quartile of
      skill was also associated with longer operations (137 minutes vs. 98 minutes,
      P<0.001) and higher rates of reoperation (3.4% vs. 1.6%, P=0.01) and readmission
      (6.3% vs. 2.7%) (P<0.001). CONCLUSIONS: The technical skill of practicing
      bariatric surgeons varied widely, and greater skill was associated with fewer
      postoperative complications and lower rates of reoperation, readmission, and
      visits to the emergency department. Although these findings are preliminary, they
      suggest that peer rating of operative skill may be an effective strategy for
      assessing a surgeon's proficiency.

PMID- 24106939
TI  - Case records of the Massachusetts General Hospital. Case 31-2013. A 29-year-old
      man with abdominal pain, fever, and weight loss.

PMID- 24106940
TI  - Oh, to be new.

PMID- 24106941
TI  - Cut well, sew well, do well?

PMID- 24106942
TI  - Targeted decolonization to prevent ICU infections.

PMID- 24106943
TI  - Targeted decolonization to prevent ICU infections.

PMID- 24106944
TI  - Targeted decolonization to prevent ICU infections.

PMID- 24106945
TI  - Targeted decolonization to prevent ICU infections.

PMID- 24106926
TI  - Non-AIDS defining cancers in the D:A:D Study--time trends and predictors of
      survival: a cohort study.
AB  - BACKGROUND: Non-AIDS defining cancers (NADC) are an important cause of morbidity
      and mortality in HIV-positive individuals. Using data from a large international
      cohort of HIV-positive individuals, we described the incidence of NADC from 2004
      2010, and described subsequent mortality and predictors of these. METHODS:
      Individuals were followed from 1st January 2004/enrolment in study, until the
      earliest of a new NADC, 1st February 2010, death or six months after the
      patient's last visit. Incidence rates were estimated for each year of follow-up,
      overall and stratified by gender, age and mode of HIV acquisition. Cumulative
      risk of mortality following NADC diagnosis was summarised using Kaplan-Meier
      methods, with follow-up for these analyses from the date of NADC diagnosis until
      the patient's death, 1st February 2010 or 6 months after the patient's last
      visit. Factors associated with mortality following NADC diagnosis were identified
      using multivariable Cox proportional hazards regression. RESULTS: Over 176,775
      person-years (PY), 880 (2.1%) patients developed a new NADC (incidence:
      4.98/1000PY [95% confidence interval 4.65, 5.31]). Over a third of these patients
      (327, 37.2%) had died by 1st February 2010. Time trends for lung cancer, anal
      cancer and Hodgkin's lymphoma were broadly consistent. Kaplan-Meier cumulative
      mortality estimates at 1, 3 and 5 years after NADC diagnosis were 28.2% [95% CI
      25.1-31.2], 42.0% [38.2-45.8] and 47.3% [42.4-52.2], respectively. Significant
      predictors of poorer survival after diagnosis of NADC were lung cancer (compared
      to other cancer types), male gender, non-white ethnicity, and smoking status.
      Later year of diagnosis and higher CD4 count at NADC diagnosis were associated
      with improved survival. The incidence of NADC remained stable over the period
      2004-2010 in this large observational cohort. CONCLUSIONS: The prognosis after
      diagnosis of NADC, in particular lung cancer and disseminated cancer, is poor but
      has improved somewhat over time. Modifiable risk factors, such as smoking and low
      CD4 counts, were associated with mortality following a diagnosis of NADC.

PMID- 24106946
TI  - Targeted decolonization to prevent ICU infections.

PMID- 24106948
TI  - Treatment of acute promyelocytic leukemia.

PMID- 24106947
TI  - Targeted decolonization to prevent ICU infections.

PMID- 24106949
TI  - Treatment of acute promyelocytic leukemia.

PMID- 24106950
TI  - Genomic landscapes and clonality of de novo AML.

PMID- 24106951
TI  - Genomic landscapes and clonality of de novo AML.

PMID- 24106952
TI  - Threshold insulin-pump interruption to reduce hypoglycemia.

PMID- 24106953
TI  - Threshold insulin-pump interruption to reduce hypoglycemia.

PMID- 24106954
TI  - Observation care.

PMID- 24106955
TI  - Observation care.

PMID- 24106956
TI  - Pancreatic atrophy--a new late toxic effect of sorafenib.

PMID- 24106957
TI  - Images in clinical medicine. Muller's sign.

PMID- 24106958
TI  - List-Barbas-Mannich reaction catalyzed by modularly designed organocatalysts.
AB  - The List-Barbas-Mannich reaction of ethyl (p-methoxyphenylimino)acetate (p
      methoxyphenyl = PMP) with unmodified aldehydes or ketones catalyzed by modularly
      designed organocatalysts (MDOs) that are self-assembled from proline and cinchona
      alkaloid thioureas (such as a quinidine-derived thiourea) produces the
      corresponding gamma-oxo-alpha-amino acid derivatives in high yields and excellent
      stereoselectivities. No solvent is necessary for this reaction. Aldehydes are
      especially good substrates for this reaction: The reaction takes only a few
      minutes to yield the corresponding List-Barbas-Mannich products in excellent dr
      (up to >99:1) and ee values (up to >99% ee). 

PMID- 24106959
TI  - Biophysical characterization of antimicrobial peptides activity: from in vitro to
      ex vivo techniques.
AB  - Antimicrobial peptides (AMPs) are evolutionarily conserved components of the
      innate immune defense system of many living organisms varying from prokaryotes to
      eukaryotes, including humans. Due to their broad-spectrum activity and low level
      of induced resistance, these short aminoacid sequences represent a novel class of
      potential antimicrobial agents. Besides the development of anti-bacterial drugs,
      AMPs constitute ideal molecular models for the design of molecules with wide
      ranging nanomedical applications, such as anti-tumorigenic agents and
      pharmacological tools to cure channelopaties. Several techniques are currently
      used to shed light on the mechanisms of action of AMPs, ranging from the
      characterization of the interaction between peptides and biomimetic membranes
      and/or intracellular targets, to the study of AMPs effects on pathogens, living
      cells and tissues. Comprehensive and multiscale studies are crucial to design new
      AMPs and to identify molecules that can boost their activity. In this minireview
      we summarize the most recent achievements in AMP-characterization, with a special
      emphasis on the integration of biophysical approaches, which can synergistically
      help to bridge the gap between in vitro and ex vivo investigations. 

PMID- 24106960
TI  - Receptor tyrosine kinases take a direct route to mitochondria: an overview.
AB  - Receptor tyrosine kinases (RTKs) are cell surface receptors that transmit
      extracellular signals to the interior of the cell activating multiple signaling
      cascades: the binding of specific extracellular ligands activates RTKs which act
      as a scaffold at plasma membrane level for the recruitment and activation of
      several signaling molecules. A paradigm shift emerged when an alternative direct
      signaling pathway was discovered: RTKs may move from cell surface to nucleus
      where they transduce the signals in a direct way. More recently, evidence has
      accumulated that RTKs may also translocate to mitochondria and regulate their
      functions, i.e., by altering tyrosine phosphorylation of specific mitochondrial
      proteins. This latter emerging pathway is here reviewed and discussed. 

PMID- 24106961
TI  - Clostridial neurotoxins: mode of substrate recognition and novel therapy
      development.
AB  - The clostridial neurotoxins (CNTs) are among the most potent protein toxins known
      to humans. CNTs include seven serotypes (A~G) of botulinum toxins (BoNTs), which
      cause botulism, a flaccid paralysis, and tetanus toxin (TeNT), which causes
      spastic paralysis. BoNTs are classified as category A agent and may be used as
      potential bioterrorism weapons. On the other hand, the ability of an extremely
      low dosage of BoNTs (less than 1 ng) to cause reversible partial paralysis upon
      injection into muscle has turned BoNTs, in particular serotypes A and B, from
      deadly agents to novel therapeutic agents for treatment of a wide range of
      clinical conditions associated with involuntary muscle spasm and contractions. In
      addition to clinical use, they may also be used in cosmetics. Further indications
      for BoNTs will continue to be developed, although current BoNT therapies have
      encountered some limitations due to the pharmacological properties of BoNTs, such
      as their ability to elicit immunoresistance in patients upon periodical
      injections. This review summarizes the present knowledge of the mechanisms of
      action of CNTs, with particular focus on the mode of substrate recognition by CNT
      catalytic domains and knowledge regarding substrate recognition can be utilized
      to develop novel BoNT products to extend its usefulness in therapeutic
      interventions and overcome the immunoresistance problems. 

PMID- 24106962
TI  - The HIV-1 capsid protein as a drug target: recent advances and future prospects.
AB  - HIV-1, the agent responsible for AIDS, belongs to the retrovirus family. Assembly
      of the immature HIV-1 capsid occurs through the controlled polymerization of the
      Gag polyprotein, which is transported to the plasma membrane of infected cells,
      where morphogenesis of the immature, non-infectious virion occurs. Moreover, the
      mature capsid of HIV-1 is formed by the assembly of copies of the capsid protein
      (CA), which results, among other proteins, from cleavage of Gag. The C-terminal
      domain of CA (CTD) can homodimerize, and most of the dimerization interface is
      formed by a single alpha-helix from each monomer. Assembly of the HIV-1 capsid
      critically depends on CA-CA interactions, including CTD interaction with itself
      and with the N-terminal domain of CA (NTD). This review will report on recent
      advances for the search of small organic compounds and peptides that have been
      designed in the last four years to hamper CA assembly. Most of the molecules have
      been proved to interact with CA; such molecules aim to disrupt and/or alter the
      oligomerization capability of CTD and/or NTD. 

PMID- 24106963
TI  - Proteomics of the dystrophin-glycoprotein complex and dystrophinopathy.
AB  - The largest human gene is represented by the X-chromosomal dystrophin gene of 2.4
      million bases, which encodes for the membrane cytoskeletal protein dystrophin.
      The dystrophin isoform Dp427 has a subsarcolemmal location and forms a
      supramolecular membrane assembly with a variety of glycoproteins. In healthy
      muscle fibres, dystrophin acts as an actin-binding protein that links the
      cytoskeleton via the alpha/beta-dystroglycan complex to the extracellular matrix
      protein laminin. This trans-sarcolemmal complex is believed to stabilize the
      muscle surface and thus prevents membrane rupturing during excitation-contraction
      relaxation cycles. In the highly progressive muscle wasting disease Duchenne
      muscular dystrophy, the primary deficiency in dystrophin causes a drastic
      reduction in dystrophin-associated glycoproteins, which renders muscle fibres
      more susceptible to necrosis. Following the biochemical and cell biological
      characterization of the dystrophin-glycoprotein complex, several mass
      spectrometry-based proteomic studies have investigated global changes in
      dystrophin-deficient muscle tissues. This review briefly outlines the basic
      domain structure of Dp427 and the composition of the dystrophin-associated
      glycoprotein complex from skeletal muscle. A detailed discussion of recent
      proteomic analyses of the purified dystrophin-glycoprotein complex is included,
      as well as a summary of mass spectrometric surveys of dystrophic specimens. The
      study of these new areas of muscle proteomics tends to improve our understanding
      of the normal function of dystrophin in contractile fibres and better define the
      molecular mechanism of X-linked muscular dystrophy. 

PMID- 24106964
TI  - Involvement of dietary bioactive proteins and peptides in autism spectrum
      disorders.
AB  - Autism and autism spectrum disorders (ASDs) are heterogeneous, severe
      neurodevelopmental pathologies. These enigmatic conditions have their origins in
      the interaction of multiple genes and environmental factors. Dysfunctions in
      social interactions and communication skills, restricted interests, repetitive
      and stereotypic verbal and non-verbal behaviours are the main core symptoms.
      Several biochemical processes are associated with ASDs: oxidative stress;
      endoplasmic reticulum stress; decreased methylation capacity; limited production
      of glutathione; mitochondrial dysfunction; intestinal impaired permeability and
      dysbiosis; increased toxic metal burden; immune dysregulation. Current available
      treatments for ASDs can be divided into behavioural, nutritional and medical
      approaches, although no defined standard approach exists. Dietary bioactive
      proteins and peptides show potential for application as health-promoting agents.
      Nowadays, increasing studies highlight a key role of bioactive proteins and
      peptides in ASDs. This review will focus on the state-of-the-art regarding the
      involvement of dietary bioactive proteins and peptides in ASDs. Identification of
      novel therapeutic targets for ASD management will be also discussed. 

PMID- 24106965
TI  - The neuropeptide galanin benefits insulin sensitivity in subjects with type 2
      diabetes.
AB  - Impaired insulin sensitivity, namely insulin resistance, is a metabolic and
      functional disorder that is often associated with the type 2 diabetes mellitus
      and/or obesity. Recent studies have provided compelling clues that the
      neuropeptide galanin is closely related to insulin sensitivity in skeletal muscle
      and adipose tissue of rats. This peptide may regulate glucose homeostasis and
      carbohydrate metabolism in peripheral tissues, as well as accelerate the
      translocation of glucose transporter 4 to the plasma membrane of various insulin
      sensitive cells to reduce insulin resistance. Galanin plays a crucial role in
      inhibiting insulin secretion from pancreatic beta cells to prevent
      hyperinsulinemia, which is a characteristic of type 2 diabetes mellitus. This
      review provides a comprehensive aggregation of the current literature available,
      bringing together data gleaned from our recent studies highlighting the role of
      galanin in regulating insulin sensitivity. This comprehensive role played by
      galanin and its relative agents in regulating insulin secretion and insulin
      sensitivity provides a new insight into the influence of this neuropeptides on
      the prevention and treatment of type 2 diabetes mellitus. 

PMID- 24106966
TI  - Insect inducible antimicrobial peptides and their applications.
AB  - Antimicrobial peptides (AMPs) are found as important components of the innate
      immune system (host defense) of all invertebrates. These peptides can be
      constitutively expressed or induced in response to microbial infections. Indeed,
      they vary in their amino acid sequences, potency and antimicrobial activity
      spectra. The smaller AMPs act greatly by disrupting the structure or function of
      microbial cell membranes. Here, the insect innate immune system with emphasis on
      inducible antimicrobial peptide properties against microbial invaders has been
      discussed. 

PMID- 24106967
TI  - Implications of angiotensin II in central nervous system on exercise performance.
AB  - The renin-angiotensin system (RAS) consists of a complex enzyme-peptide system,
      which, besides from functioning as a circulating endocrine system, is also
      intrinsic in many organs and tissues, including the brain. Although the RAS
      generates a family of biological active peptides, angiotensin II (Ang II) is
      still considered one of its main mediators and effectors. Ang II produces many
      well defined and potent effects through AT1 and AT2 receptors and its
      physiological applications are yet expanding. Recently, it has been proposed that
      Ang II, acting both centrally and peripherally, interferes on exercise
      performance due to its influence on multiple functions within the organism. This
      hypothesis is also supported by evidences reporting an increased frequency of the
      ACE I allele among elite athletes, suggesting that this is a genetic factor that
      influences physical performance. The fatigue resulting from physical exercise is
      a multifactorial phenomenon that comprises the interaction between physiological
      factors of peripheral and/or central origin. To that extent, the Ang II-mediated
      events on factors that affect exercise performance such as cardiovascular,
      metabolic and thermoregulatory adjustments as well as cerebral metabolism and
      neurohumoral or neurotransmitter turnover, implicate the peptide in the genesis
      of exercise-induced fatigue. This mini-review focuses on how exercise-induced
      physiological adjustments are influenced by Ang II within the central nervous
      system and how these effects may limit athletic performance. 

PMID- 24106968
TI  - Functional switch from pro-neurotrophins to mature neurotrophins.
AB  - Growing evidence has shown that the proforms of several neurotrophins, e.g.,
      nerve growth factor (NGF), brain-derived neurotrophic factor (BDNF),
      neurotrophin3 (NT3) can be synthesized, secreted from neurons or glial cells and
      function actively in mammalian nervous system. By the intracellular and
      extracellular enzymatic cleavage processing, mature neurotrophins are generated
      and exert their functions in the developing, physiological and pathological
      activities. While mature neurotrophins exhibit neuroprotective roles via tyrosine
      kinase receptors (TrkA, TrkB and TrkC), the proforms of neurotrophins show
      totally-different biological effects that may induce apoptotic cell death of
      neurons by triggering p75NTR-sortilin signaling cascades. In addition, another
      key neurotrophic factor named glial-derived neurotrophic factor (GDNF) also
      appears to be a product generated from proGDNF, and its cleavage and potential
      biological function of proGDNF remains an unrevealed problem. Obviously,
      accumulating studies indicated that the exact or timely cleavage processing
      should be essential for the functional switch from proneurotrophins to mature
      neurotrophins, while dysfunction in the enzymatic cleavage, aberrant
      extracellular release, and abnormal subunit organization of binding receptors
      might be also crucially involved in neurodegeneration of the central neurons,
      pathogenesis, and even disease progression of various neurodegenerative diseases
      in human beings. 

PMID- 24106970
TI  - Influence of feeding and intracoronary dose on insulin-mediated relative akt
      phosphorylation in the porcine myocardium.
AB  - AIMS: Insulin promotes Akt-dependent prosurvival signaling and reduces
      experimental ischemia reperfusion injury, but its clinical impact has been
      limited. Further understanding of the interplay between insulin and Akt in the
      myocardium of relevant large animal models is needed. We aimed to investigate (1)
      Akt phosphorylation, (2) influence of feeding state, and (3) impact of dose on
      the Akt response following intracoronary insulin administration in the
      nonischemic porcine heart. METHODS: Pigs fed 2 h preprocedure received 0.1 U
      (unit) or 1.0 U of insulin in the left coronary artery and fasting pigs 0.1 U.
      Left and right ventricle tissues harvested 15 min postinsulin administration were
      analyzed for Akt phosphorylation by densitometric analyses of total Akt and
      phosphorylated Akt immunoblots expressed as a ratio and normalized against left
      auricle biopsies at baseline. RESULTS: Median relative Akt phosphorylation across
      all biopsy locations increased significantly from baseline in both fasting and
      fed animals after insulin infusion: 371.4% (P < 0.001) in the fasting-0.1 U
      insulin group, 202.7% (P = 0.003) in the fed-1.0 U group and 131.5% (P < 0.001)
      in the fed-0.1 U group. The increase was significantly higher for the fasting-0.1
      U and the fed-1.0 U groups as compared with the fed-0.1 U group. Baseline serum
      glucose in fed and fasting pigs was 6.3 +/- 0.3 versus 5.2 +/- 0.4 mm (P =
      0.050), respectively. CONCLUSIONS: Preexperimental feeding attenuates the median
      relative rise in Akt phosphorylation mediated by exogenous insulin in the porcine
      heart, and higher insulin doses are therefore required in fed compared with
      fasting animals.

PMID- 24106969
TI  - The influence of medical testing on patients' health: an overview from the
      gynecologists' perspective.
AB  - BACKGROUND: A medical tests may influence the health of patients by guiding
      clinical decisions, such as treatment in case of a positive test result. However,
      a medical test can influence the health of patients through other mechanisms as
      well, like giving reassurance. To make a clinical recommendation about a medical
      test, we should be aware of the full range of effects of that test on patients.
      This requires an understanding of the range of effects that medical testing can
      have on patients. This study evaluates the mechanisms through which medical
      testing can influence patients' health, other than the effect on clinical
      management, from a gynecologist's perspective. METHODS: A qualitative study in
      which explorative focus groups were conducted with gynecologists, gynecological
      residents and gynecological M.D. researchers (n = 43). Discussions were
      transcribed verbatim. Transcriptions were coded inductively and analyzed by three
      researchers. RESULTS: All participants contributed various clinical examples in
      which medical testing had influenced patients' health. Clinical examples
      illustrated that testing, in itself or in interaction with contextual factors,
      may provoke a wide range of effects on patients. Our data showed that testing can
      influence the doctor's perceptions of the patients' appraisal of their illness,
      their perceived control, or the doctor-patient relationship. This may lead to
      changes in psychological, behavioral, and/or medical outcomes, both favorably or
      unfavorably. The data were used to construct a conceptual framework of effects of
      medical testing on patients. CONCLUSIONS: Besides supporting clinical decision
      making, medical testing may have favorable or unfavorable effects on patients'
      health though several mechanisms.

PMID- 24106971
TI  - General principles and methods for routine automated microRNA in situ
      hybridization and double labeling with immunohistochemistry.
AB  - MicroRNAs (miRNAs) are small non-coding RNAs that modulate gene expression by
      binding to complementary sequences on target messenger RNA transcripts. Changes
      in the expression levels of specific miRNAs have been associated with a variety
      of disease conditions. We developed a reliable and high throughput in situ
      hybridization (ISH) method and optimized tissue fixation conditions for formalin
      fixed, paraffin embedded (FFPE) tissues. ISH methods were automated to visualize
      four miRNAs: miRNA-145 (smooth muscle cells), miRNA-126 (endothelial cells),
      miRNA-21 (neoplastic cells) and U6 small nuclear RNA (nuclear marker) using
      locked nucleic acid (LNA) probes and the Discovery Ultra Ventana(TM) platform.
      The FFPE tissue sections were pretreated with protease 3, hybridized with probe
      concentrations of <= 25 nM; signal was detected using an enhanced, polymer-based
      detection method. The ISH signal was stronger and more uniform for tissue samples
      fixed for >= 48 h. To investigate the specificity of the method, we developed an
      automated dual ISH for miRNA-145 coupled with immunohistochemistry for smooth
      muscle actin, which confirmed the specific distribution of miRNA-145 to smooth
      muscle cells. These methods may be used routinely for exploratory studies of
      biomarker development, sample screening and understanding the role of miRNA in
      the pathophysiology of specific diseases.

PMID- 24106972
TI  - Effects of Piper hispidinervum on spermatogenesis and histochemistry of ovarioles
      of Spodoptera frugiperda.
AB  - The fall armyworm, Spodoptera frugiperda (J. E. Smith) (Lepidoptera: Noctuidae),
      not only damages crops, but controlling its population also requires synthetic
      insecticides, which leads to selection of resistant populations and environmental
      contamination. Essential oils are an alternative for controlling this insect.
      There are few studies of the effects of these oils on the insect's reproductive
      system. We evaluated the effects of the long pepper, Piper hispidinervum,
      essential oil on the gonads of the armyworm and tested its possible influence on
      the fertility of this insect. Dosages of 30 and 50 mg/ml were tested in 3(rd)
      instar caterpillars using the leaf immersion method. Testes and ovarioles were
      collected, fixed with 10% formalin and embedded in Historesin. The sections were
      stained with toluidine blue and Mallory trichrome to detect connective tissue,
      periodic acid-Schiff to detect neutral carbohydrates, and bromophenol blue to
      detect proteins. We found that the long pepper essential oil affected negatively
      the spermatogenesis and altered the histochemistry of the ovarioles of S.
      frugiperda. The effects of long pepper oil suggest that it is a promising tool
      for controlling the armyworm pest.

PMID- 24106973
TI  - An inexpensive alternative to routine section adhesives for histology: the
      mucilaginous substance of the Assyrian plum.
AB  - We found that the mucilaginous substance of the Assyrian plum, Cordia myxa, can
      be used as an adhesive for attaching sections of animal tissues to slides. Unlike
      Mayer's albumen, this material left no stainable residue and had no noticeable
      effect on the histological structure of the tissue sections. The mucilaginous
      substance of C. myxa is a useful and inexpensive alternative to standard
      adhesives.

PMID- 24106974
TI  - Association between fat-mass-and-obesity-associated (FTO) gene and hip fracture
      susceptibility.
AB  - OBJECTIVE: Common variants in the fat-mass-and-obesity-associated (FTO) gene are
      related to body mass index (BMI), which is a predictor of hip fracture risk. This
      study sought to examine the association between variants in the FTO gene and hip
      fracture risk. DESIGN AND PARTICIPANTS: This is a prospective study including 934
      postmenopausal women aged 60 years and above living in Dubbo, Australia (Dubbo
      Osteoporosis Epidemiology Study), followed up between 1989 and 2007.
      MEASUREMENTS: Six single nucleotide polymorphisms (SNPs) (rs1421085, rs1558902,
      rs1121980, rs17817449, rs9939609 and rs9930506) of the FTO gene were genotyped
      using Taqman assay. Bone mineral density at the lumbar spine and femoral neck was
      measured by DXA (GE-Lunar) at baseline. Incidence of hip fractures during the
      follow-up was ascertained by reviewing X-ray reports. We used Cox's models to
      estimate the association between the genetic variants and hip fracture risk. We
      also utilized Bayes factor to evaluate the association. RESULTS: One hundred and
      two women (11%) had sustained a hip fracture. The incidence of hip fracture was
      greater in women homozygous for the minor allele of all SNPs. Women homozygous
      for the minor allele (AA) of rs1121980 had significantly higher risk of hip
      fracture (hazard ratio, 2.06; 95% CI 1.17-3.62) than women homozygous for the
      major allele (TT). The observed data favoured the hypothesis of FTO gene and
      fracture association over the hypothesis of nonassociation by a factor of nine.
      CONCLUSION: Common variations in the FTO gene are associated with hip fracture
      risk in women and that FTO gene may help improve the predictive value of hip
      fracture risk.

PMID- 24106975
TI  - Are sexes affected differently by ketamine? An exploratory study in ketamine
      users.
AB  - One hundred primary ketamine users and 100 controls were recruited in Hong Kong
      between December 2009 and December 2011. Cognitive assessment included general
      intelligence, working, verbal, and visual memory, and executive functions. A
      Univariate General Linear Model was used to compare cognitive performance between
      the male and female ketamine users and controls. The female users appeared to
      have a higher risk of visual memory impairment than their male counterparts.
      Further studies are warranted to clarify the mechanism of the sex-specific effect
      of ketamine on cognitive functions. 

PMID- 24106976
TI  - Family discord is associated with increased substance use for pregnant substance
      users.
AB  - Childhood abuse and partner violence are associated with prenatal substance
      abuse, but the potential impact of current family discord, which reflects broader
      family relationships and encompasses problems less severe than violence, has had
      little evaluation in pregnant substance users. Using data from 196 pregnant
      substance users participating in a NIDA Clinical Trials Network randomized
      clinical trial, we examined the relationship of baseline family discord to
      substance use and treatment session attendance. Family discord was assessed using
      items from the family composite of the Addiction Severity Index. Substance use
      was assessed by the Substance Use Calendar and urine drug screens (UDS).
      Assessments were weekly for four weeks and at two- and four-month post
      randomization. Women with family discord were more likely to report living with a
      problematic substance user, reported a higher percentage of substance use days
      throughout each study phase, had a greater proportion of positive UDS over the
      four-month study period, and attended more weeks of treatment during the first
      month. Specific treatment interventions targeting pregnant women with family
      discord may be warranted. 

PMID- 24106977
TI  - Thallium mercury chalcobromides, TlHg6Q4Br5 (Q = S, Se).
AB  - The new compounds TlHg6Q4Br5 (Q = S, Se) are reported along with their syntheses,
      crystal structures, and thermal and optical properties, as well as electronic
      band structure calculations. Both compounds crystallize in the tetragonal I4/m
      space group with a = 14.145(1) A, c = 8.803(1) A, and dcalc = 7.299 g/cm(3) for
      TlHg6S4Br5 (compound 1) and a = 14.518(2) A, c = 8.782(1) A, and dcalc = 7.619
      g/cm(3) for TlHg6Se4Br5 (compound 2). They consist of cuboid Hg12Q8 building
      units interconnected by trigonal pyramids of BrHg3, forming a three-dimensional
      structure. The interstitial spaces are filled with thallium and bromide ions.
      Compounds 1 and 2 melt incongruently and show band gaps of 3.03 and 2.80 eV,
      respectively, which agree well with the calculated ones. First-principles
      electronic structure calculations at the density functional theory level reveal
      that both compounds have indirect band gaps, but there also exist direct
      transitions at energies similar to the indirect gaps. 

PMID- 24106978
TI  - Sexual self-regulation and cognitive absorption as factors of sexual response
      toward virtual characters.
AB  - The eye movements and penile responses of 20 male participants were recorded
      while they were immersed with virtual sexual stimuli. These participants were
      divided into two groups according to their capacity to focus their attention in
      immersion (high and low focus). In order to understand sexual self-regulation
      better, we subjected participants to three experimental conditions: (a) immersion
      with a preferred sexual stimulus, without sexual inhibition; (b) immersion with a
      preferred sexual stimulus, with sexual inhibition; and (c) immersion with a
      neutral stimulus. A significant difference was observed between the effects of
      each condition on erectile response and scanpath. The groups differed on self
      regulation of their erectile responses and on their scanpath patterns. High focus
      participants had more difficulties than low focus participants with inhibiting
      their sexual responses and displayed less scattered eye movement trajectories
      over the critical areas of the virtual sexual stimuli. Results are interpreted in
      terms of sexual self-regulation and cognitive absorption in virtual immersion. In
      addition, the use of validated virtual sexual stimuli is presented as a
      methodological improvement over static and moving pictures, since it paves the
      way for the study of the role of social interaction in an ecologically valid and
      well-controlled way.

PMID- 24106979
TI  - Cyberstalking in a large sample of social network users: prevalence,
      characteristics, and impact upon victims.
AB  - The aim of this study was to determine the prevalence of cyberstalking
      victimization, characteristics of victims and offenders, and the impact of
      cyberstalking on the victims' well-being and mental health. An online survey of
      6,379 participants was carried out, involving users of the German social network
      StudiVZ. Subjective mental health status was assessed with the WHO-5 well-being
      index. The prevalence of cyberstalking was estimated at 6.3%. In various aspects,
      cyberstalking was comparable to offline stalking: cyberstalking occurred most
      often in the context of ex-partner relationships; most of the victims were female
      and the majority of the perpetrators were male. Compared to non-victims, victims
      of cyberstalking scored significantly poorer on the WHO-5 well-being index. The
      prevalence of cyberstalking is considerable. However, if stringent definition
      criteria comparable to those of offline stalking are applied, it is not a mass
      phenomenon. The negative impact of cyberstalking on the victims' well-being
      appears similar to that of offline stalking. Hence, cyberstalking should be taken
      as seriously as offline variants of stalking by legal authorities and victim
      assistance professionals.

PMID- 24106981
TI  - Fine and ultrafine particle emissions from microwave popcorn.
AB  - This study characterized fine (PM2.5 ) and ultrafine particle (UFP, diameter <
      100 nm) emissions from microwave popcorn and analyzed influential factors. Each
      pre-packed popcorn bag was cooked in a microwave oven enclosed in a stainless
      steel chamber for 3 min. The number concentration and size distribution of UFPs
      and PM2.5 mass concentration were measured inside the chamber repeatedly for five
      different flavors under four increasing power settings using either the foil
      lined original package or a brown paper bag. UFPs and PM2.5 generated by
      microwaving popcorn were 150-560 and 350-800 times higher than the emissions from
      microwaving water, respectively. About 90% of the total particles emitted were in
      the ultrafine size range. The emitted PM concentrations varied significantly with
      flavor. Replacing the foil-lined original package with a brown paper bag
      significantly reduced the peak concentration by 24-87% for total particle number
      and 36-70% for PM2.5 . A positive relationship was observed between both UFP
      number and PM2.5 mass and power setting. The emission rates of microwave popcorn
      ranged from 1.9 * 10(10) to 8.0 * 10(10) No./min for total particle number and
      from 134 to 249 MUg/min for PM2.5 . 

PMID- 24106980
TI  - MicroRNAs: key players of taxane resistance and their therapeutic potential in
      human cancers.
AB  - The successful long-term use of taxane for cancer therapy is often prevented by
      the development of drug resistance in clinic. Thus, exploring the mechanisms
      involved is a first step towards rational strategies to overcome taxane
      resistance. Taxane resistance-related microRNA (miRNAs) are under investigation
      and miRNAs could induce the taxane resistance of tumour cells by regulating cell
      cycle distribution, survival and/or apoptosis pathways, drug transports,
      epithelial-mesenchymal transition and cancer stem cell. This article summarizes
      current research involving miRNAs as regulators of key target genes for tanxanxe
      chemoresistance and discusses the complex regulatory networks of miRNAs. Also,
      the authors will envisage future developments towards the potential use of
      targeting miRNAs as a novel strategy for improving response of tumour patients to
      taxane. miRNAs play critical roles in taxane chemoresistance and the miRNA-based
      therapies will be helpful for overcoming drug resistance and developing more
      effective personalized anti-cancer treatment strategies. Further research studies
      should be performed to promote therapeutic-clinical use of taxane resistance
      related miRNAs in cancer patients, especially in those patients with taxane
      resistant cancers. 

PMID- 24106983
TI  - Impact of cytotoxic and targeted antineoplastic drugs on the validity of the
      mitogen-induced interferon-gamma release assay for latent tuberculosis infection:
      results of a prospective trial at a comprehensive cancer center.
AB  - Abstract The T-SPOT.TB test (TS.TB), an interferon-gamma (IFN-gamma) release
      assay (IGRA), is superior in diagnosing latent tuberculosis infection compared
      with the conventional tuberculin skin test (TST). However, whether cytotoxic
      chemotherapy and treatment with new-generation antineoplastic monoclonal
      antibodies affects the TS.TB is not certain. We evaluated the feasibility of
      using the TS.TB in this population. Sixteen cancer patients at high risk for
      tuberculosis exposure were prospectively evaluated with the TST and TS.TB. Blood
      samples were obtained 7.5 +/- 89.3 days after the most recent cycle of
      antineoplastic therapy. Six patients (38%) were febrile within 24 h of blood
      sampling; high-dose corticosteroid therapy and profound treatment-induced
      neutropenia were present in 1 patient each. In all patients, TS.TB showed no
      evidence of latent tuberculosis infection. A robust mitogen-induced IFN-gamma
      response was seen in samples from 14 patients (88%) despite therapy with high
      dose corticosteroids, cyclophosphamide, fludarabine, gemtuzumab ozogamicin, and
      alemtuzumab. The presence of fever or profound neutropenia did not negatively
      impact mitogen response by peripheral lymphocytes. The 2 patients whose
      peripheral blood lymphocytes (> 500 cells/ml) failed to generate a cytokine
      response to ex vivo mitogen stimulation had refractory advanced cancer. Unlike
      the TST, a negative TS.TB provided interpretable results even in cancer patients
      undergoing new-generation immunosuppressive therapy. 

PMID- 24106982
TI  - Furanylazaindoles: potent anticancer agents in vitro and in vivo.
AB  - Preliminary biological data on 7-anilino-6-azaindoles (8-11) suggested that
      hydrophobic substituents at C7 contribute to enhancement of antiproliferative
      activity. A novel series of 7-aryl-6-azaindole-1-benzenesulfonamides (12-22) were
      developed and showed improved cytotoxicity compared to ABT751 (5). The conversion
      of C7 phenyl rings into C7 heterocycles led to a remarkable improvement of
      antiproliferative activity. Among all the synthetic products, 7-(2-furanyl)-1-(4
      methoxybenzenesulfonyl)-6-azaindole (21) exhibited the most potent anticancer
      activity against KB, HT29, MKN45, and H460 cancer cell lines with IC50 values of
      21.1, 32.0, 27.5, and 40.0 nM, respectively. Bioassays indicated that 21 not only
      inhibits tubulin polymerization by binding to tubulin at the colchicine binding
      site but also arrests the cell cycle at the G2/M phase with slight arrest at the
      sub-G1 phase. Compound 21 also functions as a vascular disrupting agent and dose
      dependently inhibits tumor growth without significant change of body weight in an
      HT29 xenograft mouse model. Taken together, compound 21 has potential for further
      development as a novel class of anticancer agents.

PMID- 24106984
TI  - Clinical differences in Clostridium difficile infection based on age: a
      multicenter study.
AB  - Advancing age is a well-known risk factor for Clostridium difficile infection
      (CDI). However, age-specific clinical differences in CDI are uncertain. A
      retrospective comparative analysis was performed based on age in 1367 patients
      with CDI in Korea. Most clinical features were similar in the two age groups
      studied, however malignancy was more common in the older group (age >= 65 y) (p <
      0.001), while chemotherapy and transplantation were more common in the younger
      group (age < 65 y) (p < 0.001). Endoscopic examinations were more commonly
      performed in the older group (p = 0.010), which had a high positive predictive
      value (88.3%). More patients recovered from CDI without specific antibiotic
      treatment in the younger group than in the older group (p < 0.001). Although
      advancing age is an important risk factor for CDI, the clinical features of
      younger patients are similar to those of the older patient population.

PMID- 24106985
TI  - Thoracoscopic pericardial window for management of pericardial effusion in 15
      dogs.
AB  - OBJECTIVES: To report short-term complications and long-term outcomes of
      thoracoscopic pericardial window for management of pericardial effusion in dogs.
      METHODS: Retrospective study of dogs in which thoracoscopic pericardial window
      was performed using a three-cannula technique. Surgery time, complications,
      postoperative management, area of resected pericardium, histopathology results
      and outcome were evaluated. RESULTS: Diagnoses included dogs with idiopathic
      pericardial effusion (n = 10), cardiac mass (n = 4) and mesothelioma (n = 1). One
      case required conversion to sternotomy. Median thoracoscopic surgery time was 52
      . 5 (range, 45-80) minutes. Complications occurred in four (26%) cases. Median
      time to discharge was one (range, 1-6) day. Of dogs with idiopathic pericardial
      effusion, one is alive at 150 days, one was lost to follow-up at 180 days while
      eight were euthanased of which five were for unrelated reasons. All dogs with
      neoplastic causes died or were euthanased because of their illness. Median
      survival time for dogs with idiopathic pericardial effusion (635 days; range, 70
      1165) was significantly longer than that for dogs with neoplasia (30 days; range,
      1-107). CLINICAL SIGNIFICANCE: Thoracoscopic pericardial window is of low
      morbidity with short surgery and hospitalisation times. It provides good long
      term control of idiopathic pericardial effusion but short-term palliation of
      clinical signs in dogs with neoplastic disease.

PMID- 24106986
TI  - A structural study of ion permeation in OmpF porin from anomalous X-ray
      diffraction and molecular dynamics simulations.
AB  - OmpF, a multiionic porin from Escherichia coli, is a useful protypical model
      system for addressing general questions about electrostatic interactions in the
      confinement of an aqueous molecular pore. Here, favorable anion locations in the
      OmpF pore were mapped by anomalous X-ray scattering of Br(-) ions from four
      different crystal structures and compared with Mg(2+) sites and Rb(+) sites from
      a previous anomalous diffraction study to provide a complete picture of cation
      and anion transfer paths along the OmpF channel. By comparing structures with
      various crystallization conditions, we find that anions bind in discrete clusters
      along the entire length of the OmpF pore, whereas cations find conserved binding
      sites with the extracellular, surface-exposed loops. Results from molecular
      dynamics simulations are consistent with the experimental data and help highlight
      the critical residues that preferentially contact either cations or anions during
      permeation. Analysis of these results provides new insights into the molecular
      mechanisms that determine ion selectivity in OmpF porin.

PMID- 24106988
TI  - Tapping into technology.

PMID- 24106987
TI  - Design of a prospective study on mental health and quality of life of maltreated
      children (aged 5-16 years) after a report to an advice and reporting center on
      child abuse and neglect.
AB  - BACKGROUND: Child maltreatment is recognized as a widespread problem with huge
      implications for mental health and quality of life. Studies have repeatedly shown
      that victims of child maltreatment report significantly more adverse life
      outcomes than non-victims. The main objective of the study is (1) to examine the
      mental health and quality of life of maltreated children over a 1.5 year period
      beginning shortly after a report has been filed with an Advies- en Meldpunt
      Kindermishandeling (AMK) (advice and reporting center on child abuse and
      neglect). Secondary objectives are: (2) to examine how relevant determinants
      influence the mental health and quality of life of maltreated children, and (3)
      to examine differences in mental health and quality of life outcomes when
      comparing families of Dutch origin with families originating from Morocco and
      Suriname. METHODS/DESIGN: A prospective study will be performed, in which parent
      child dyads will be followed over a 1.5 year period. Participants will be
      recruited shortly after the report to the AMK and they will be asked to complete
      a questionnaire four times, at baseline and every six months thereafter. Data
      will be analyzed using a longitudinal multi-level analysis. DISCUSSION: The study
      is expected to yield evidence about the mental health and quality of life of
      maltreated children and about determinants that influence their mental health and
      quality of life outcomes. Strengths of this study are (1) the design which makes
      it possible to start examining outcomes shortly after or even during the actual
      maltreatment and to follow parent-child dyads for 1.5 years, and (2) asking
      children as informants about their own situation by making use of self-report
      questionnaires as much as possible. Limitations include the risks of selection
      bias and loss to follow-up during 1.5 years of data collection. TRIAL
      REGISTRATION: NTR3674, funded by ZonMw, project 15700.2012.

PMID- 24106989
TI  - Photoresponsive fluorescent reduced graphene oxide by spiropyran conjugated
      hyaluronic acid for in vivo imaging and target delivery.
AB  - This present article demonstrates the strategy to prepare photoresponsive reduced
      graphene oxide with mussel inspired adhesive material dopamine (DN) and
      photochromic dye spiropyran (SP) conjugated to the backbone of the targeting
      ligand hyaluronic acid (HA; HA-SP). Graphene oxide (GO) was reduced by prepared
      HA-SP accepting the advantages of catechol chemistry under mildly alkaline
      condition enabling to achieve functionalized graphene (rGO/HA-SP) as fluorescent
      nanoparticles. Due to containing HA, rGO/HA-SP can bind to the CD44 cell
      receptors. The prepared rGO/HA-SP is able to retain its photochromic features and
      can be converted to merocyanine (MC) form upon irradiation with UV light
      (wavelength: 365 nm) displaying purple color. Photochromic behavior of rGO/HA-SP
      was monitored by UV-vis and fluorescence spectroscopy. In vitro fluorescence
      behavior, examined by confocal laser scanning microscope (CLSM), of rGO/HA-SP in
      cancerous A549 cell lines assured that efficient delivery of rGO/HA-SP was gained
      due to HA as targeting ligand. In this work, we have shown that in vivo
      fluorescence image of spiropyran is possible by administrating MC form solution
      of rGO/HA-SP using Balb/C mice as in vivo modal. Accumulation of rGO/HA-SP in
      tumor tissue from biodistribution analysis strongly supports the specific
      delivery of prepared graphene to the target destination. The well tuned drug
      release manner from the surface of rGO/HA-SP strongly recommends the developed
      material not only as fluorescent probe for diagnosis but also as a drug carrier
      in drug delivery system. 

PMID- 24106990
TI  - Evidence of enhanced mobility at the free surface of supported polymer films by
      in situ variable-temperature time-of-flight-secondary ion mass spectrometry.
AB  - Time-of-flight secondary ion mass spectrometry (TOF-SIMS) spectra of polystyrene
      (PS) films supported on silicon wafers were obtained at temperatures ranging from
      room temperature to 100  degrees C. Principal component analysis (PCA) of the TOF
      SIMS data revealed a transition temperature (TT) at which the surface structure
      of PS was rearranged. The TT of a 120-nm thick PS (weight-average molecular
      weight of 3,000 g/mol) thin film was determined to be about 36  degrees C, which
      is approximately 30  degrees C lower than the bulk glass transition temperature
      (Tg) of that PS. Similar TTs were observed on PSs with different molecular
      weights. As the TT is strongly related to the Tg and dependent on the molecular
      weight, it is believed that the TT determined by TOF-SIMS is related to the
      surface glass transition temperature (Tg(S)) measured by other techniques. This
      suggests that TOF-SIMS combined with PCA can be used to determine the Tg(S) of
      polymer films. Furthermore, the detailed PCA analyses indicate that the phenyl
      groups of PS tended to move away from the surface at temperatures above TT. This
      conclusion was further confirmed by contact angle and XPS measurements.

PMID- 24106991
TI  - Antioxidant profile of salivary glands in high fat diet-induced insulin
      resistance rats.
AB  - OBJECTIVE: There is no study analyzing the salivary antioxidant profile in the
      course of the insulin resistance. MATERIALS AND METHODS: Rats were divided into
      two groups. One group was fed with a normal diet, another one with a high fat
      diet for 5 weeks. The analysis included: catalase (CAT), superoxide dismutase,
      peroxidase activities, uric acid, and total antioxidant status concentrations.
      RESULTS: The activity of peroxidase in both kind of glands of insulin resistance
      rats was significantly reduced than in the control rats. The protein
      concentration, total amount of total antioxidant status in the parotid glands of
      insulin resistance rats were significantly lower than in the control glands The
      total amount of superoxide dismutase, CAT, and uric acid in the parotid glands of
      insulin resistance rats were significantly elevated in comparison with the
      control rats. The median values of the total amount of superoxide dismutase, CAT,
      peroxidase, total antioxidant status were significantly higher in the parotid
      than in the submandibular glands of the insulin resistance and control rats.
      CONCLUSION: Parotid and submandibular glands of rats react differently when
      exposed to insulin resistance condition; however, the parotid glands seem to be
      more affected. The main source of antioxidants is parotid glands of rats.

PMID- 24106992
TI  - The antiribosomal P antibodies really elicit autoimmune hepatitis?

PMID- 24106993
TI  - Impact factors and their relevance to journal quality.

PMID- 24106995
TI  - Potential pitfalls of reconstructing deep time evolutionary history with only
      extant data, a case study using the canidae (mammalia, carnivora).
AB  - Reconstructing evolutionary patterns and their underlying processes is a central
      goal in biology. Yet many analyses of deep evolutionary histories assume that
      data from the fossil record is too incomplete to include, and rely solely on
      databases of extant taxa. Excluding fossil taxa assumes that character state
      distributions across living taxa are faithful representations of a clade's entire
      evolutionary history. Many factors can make this assumption problematic. Fossil
      taxa do not simply lead-up to extant taxa; they represent now-extinct lineages
      that can substantially impact interpretations of character evolution for extant
      groups. Here, we analyze body mass data for extant and fossil canids (dogs,
      foxes, and relatives) for changes in mean and variance through time. AIC-based
      model selection recovered distinct models for each of eight canid subgroups. We
      compared model fit of parameter estimates for (1) extant data alone and (2)
      extant and fossil data, demonstrating that the latter performs significantly
      better. Moreover, extant-only analyses result in unrealistically low estimates of
      ancestral mass. Although fossil data are not always available, reconstructions of
      deep-time organismal evolution in the absence of deep-time data can be highly
      inaccurate, and we argue that every effort should be made to include fossil data
      in macroevolutionary studies. 

PMID- 24106994
TI  - Genetic and biochemical markers of hydroxyurea therapeutic response in sickle
      cell anemia.
AB  - BACKGROUND: Sickle cell anemia (SCA) presents a complex pathophysiology which can
      be affected by a number of modifying factors, including genetic and biochemical
      ones. In Brazil, there have been no studies verifying betaS-haplotypes effect on
      oxidative stress parameters. This study evaluated betaS-haplotypes and Hb F
      levels effects on oxidative stress markers and their relationship with
      hydroxyurea (HU) treatment in SCA patients. METHODS: The studied group was
      composed by 28 SCA patients. Thirteen of these patients were treated with HU and
      15 of them were not. We used molecular methodology (PCR-RFLP) for hemoglobin S
      genotype confirmation and haplotypes identification. Biochemical parameters were
      measured using spectrophotometric methods (Thiobarbituric-acid-reactive
      substances and Trolox equivalent antioxidant capacity levels, catalase and GST
      activities) and plasma glutathione levels by High-performance liquid
      chromatography coupled to electrochemical detection. RESULTS: We found the
      highest frequency of Bantu haplotype (48.2%) which was followed by Benin (32.1%).
      We observed also the presence of Cameroon haplotype, rare in Brazilian population
      and 19.7% of atypical haplotypes. The protective Hb F effect was confirmed in SCA
      patients because these patients showed an increase in Hb F levels that resulted
      in a 41.3% decrease on the lipid peroxidation levels (r =-0.74, p=0.01). Other
      biochemical parameters have not shown differential expression according to
      patient's haplotypes. Bantu haplotype presence was related to the highest lipid
      peroxidation levels in patients (p < 0,01), but it also conferred a differential
      response to HU treatment, raising Hb F levels in 52.6% (p = 0.03) when compared
      with the group with the same molecular profile without HU usage. CONCLUSIONS: SCA
      patients with Bantu haplotype showed the worst oxidative status. However these
      patients also demonstrated a better response to the treatment with HU. Such
      treatment seems to have presented a "haplotype-dependent" pharmacological effect.

PMID- 24106997
TI  - Protocol for a randomised blocked design study using telephone and text-messaging
      to support cardiac patients with diabetes: a cross cultural international
      collaborative project.
AB  - BACKGROUND: The prevalence of type 2 diabetes is rising internationally. Patients
      with diabetes have a higher risk of cardiovascular events accounting for
      substantial premature morbidity and mortality, and health care expenditure. Given
      healthcare workforce limitations, there is a need to improve interventions that
      promote positive self-management behaviours that enable patients to manage their
      chronic conditions effectively, across different cultural contexts. Previous
      studies have evaluated the feasibility of including telephone and Short Message
      Service (SMS) follow up in chronic disease self-management programs, but only for
      single diseases or in one specific population. Therefore, the aim of this study
      is to evaluate the feasibility and short-term efficacy of incorporating telephone
      and text messaging to support the care of patients with diabetes and cardiac
      disease, in Australia and in Taiwan. METHODS/DESIGN: A randomised controlled
      trial design will be used to evaluate a self-management program for people with
      diabetes and cardiac disease that incorporates the use of simple remote-access
      communication technologies. A sample size of 180 participants from Australia and
      Taiwan will be recruited and randomised in a one-to-one ratio to receive either
      the intervention in addition to usual care (intervention) or usual care alone
      (control). The intervention will consist of in-hospital education as well as
      follow up utilising personal telephone calls and SMS reminders. Primary short
      term outcomes of interest include self-care behaviours and self-efficacy assessed
      at baseline and four weeks. DISCUSSION: If the results of this investigation
      substantiate the feasibility and efficacy of the telephone and SMS intervention
      for promoting self management among patients with diabetes and cardiac disease in
      Australia and Taiwan, it will support the external validity of the intervention.
      It is anticipated that empirical data from this investigation will provide
      valuable information to inform future international collaborations, while
      providing a platform for further enhancements of the program, which has potential
      to benefit patients internationally. TRIAL REGISTRATION: ACTRN 12611001196932.

PMID- 24106998
TI  - Three-dimensional stereophotogrammetry: a novel method in volumetric measurement
      of infantile hemangioma.
AB  - Accurate and objective measurement of volume changes in infantile hemangiomas
      (IHs) is essential in routine clinical practice and clinical studies,
      particularly in the changing therapeutic landscape after the discovery of
      propranolol. Several bedside techniques for volume measurement have been
      described in the literature, but an objective method of measurement of this
      variable, dynamic vascular tumor is lacking. Three-dimensional (3D)
      phototechnology with data analysis is an up-and-coming technique in the objective
      measurement of facial volume changes. In this pilot study, the usability and
      clinical relevance of two methods of 3D stereophotogrammetry in the volume
      measurement of IH were explored. 

PMID- 24106999
TI  - Mixed tridentate pi -donor and monodentate pi -acceptor ligands as chelating
      systems for rhenium-188 and technetium-99m nitrido radiopharmaceuticals.
AB  - A new molecular metallic fragment for labeling biologically active molecules with
      99mTc and 188Re is described. This system is composed of a combination of
      tridentate pi-donor and monodentate pi-acceptor ligands bound to a [M Xi N]2+
      group (M = (99m)Tc, 188Re) in a pseudo square-pyramidal geometry. A simple
      structural model of the new metallic fragment was obtained by reacting the ligand
      2, 2'-iminodiethanethiol [H2NS2 = NH(CH2CH2SH)2] and monodentate tertiary
      phosphines with the [M Xi N]2+ group (M = (99m)Tc, (188)Re). In the resulting
      complexes (dubbed3+1complexes), the tridentate ligand binds the [M Xi N]2+ core
      through the two deprotonated, negatively charged, thiol sulfur atoms and the
      neutral, protonated, amine nitrogen atom. The residual fourth position of the
      five-coordinated arrangement is occupied by a phosphine ligand. The chemical
      identity of these model (99m)Tc and (188)Re compounds was established by
      comparison with the chromatographic properties of the corresponding complexes
      obtained at the macroscopic level with the long-lived (99)Tc and natural Re
      isotopes. The investigation was further extended to comprise a series of ligands
      formed by simple combinations of two basic amino acids or pseudo-amino acids to
      yield potential tridentate chelating systems having [S, N, S] and [N, N, S] as
      sets of pi-donor atoms. Labeling yields and in vitro stability were investigated
      using different ancillary ligands. Results showed that SNS-type ligands afforded
      the highest labeling yields and the most robust 3+1 nitrido complexes with both
      (99m)Tc and (188)Re. Thus, the new chelating system can be conveniently employed
      for labeling peptides and other biomolecules with the [M Xi N]2+ group.

PMID- 24107000
TI  - Combined NanoSIMS and synchrotron X-ray fluorescence reveal distinct cellular and
      subcellular distribution patterns of trace elements in rice tissues.
AB  - The cellular and subcellular distributions of trace elements can provide
      important clues to understanding how the elements are transported and stored in
      plant cells, but mapping their distributions is a challenging task. The
      distributions of arsenic, iron, zinc, manganese and copper, as well as
      physiologically related macro-elements, were mapped in the node, internode and
      leaf sheath of rice (Oryza sativa) using synchrotron X-ray fluorescence (S-XRF)
      and high-resolution secondary ion mass spectrometry (NanoSIMS). Although copper
      and silicon generally showed cell wall localization, arsenic, iron and zinc were
      strongly localized in the vacuoles of specific cell types. Arsenic was highly
      localized in the companion cell vacuoles of the phloem in all vascular bundles,
      showing a strong co-localization with sulfur, consistent with As(III)-thiol
      complexation. Within the node, zinc was localized in the vacuoles of the
      parenchyma cell bridge bordering the enlarged and diffuse vascular bundles,
      whereas iron and manganese were localized in the fundamental parenchyma cells,
      with iron being strongly co-localized with phosphorus in the vacuoles. The highly
      heterogeneous and contrasting distribution patterns of these elements imply
      different transport activities and/or storage capacities among different cell
      types. Sequestration of arsenic in companion cell vacuoles may explain the
      limited phloem mobility of arsenite. 

PMID- 24107001
TI  - Preparation and in vitro evaluation of etoposide-loaded PLGA microspheres for
      pulmonary drug delivery.
AB  - Pulmonary drug delivery has become a promising route in the treatment of lung
      diseases because of better local retention and lower systemic penetration. In
      this study, etoposide-loaded poly(lactic-co-glycolic acid) (PLGA) microspheres
      were designed with potential pulmonary delivery properties. The microspheres were
      prepared via improved emulsion-solvent evaporation method. Physicochemical
      characteristics, micromeritics properties and in vitro drug release behavior of
      the microspheres were then evaluated. Results showed that etoposide-loaded PLGA
      microspheres were spherical in shape with smooth surface with size (11.8 +/-
      1.25) MUm. Particles remained stable without any changing in size and morphology
      after dried by the freeze-drying method. Etoposide was loaded into PLGA
      microspheres in an amorphous state with high drug loading ((7.7 +/- 0.3)%) and
      encapsulation efficiency ((84.2 +/- 2.9)%). Results of micromeritics properties
      also demonstrated that etoposide-loaded PLGA microspheres were very suitable for
      pulmonary delivery. In addition, in vitro drug release study indicated a
      sustained release profile fitted with the Ritger-Peppas equation for up to 20
      days. In conclusion, the etoposide-loaded PLGA microspheres were promising for
      pulmonary delivery, and etoposide could be sustained released from the PLGA
      microspheres.

PMID- 24107003
TI  - Effects of correction of vitamin D insufficiency on serum osteocalcin and glucose
      metabolism in obese children.
AB  - OBJECTIVES: Osteocalcin (OCN) and vitamin D insufficiency (VDI) have been shown
      to be associated with abnormal glucose metabolism (GluMet). Whether correction of
      VDI affects serum OCN is unknown. This study evaluated the effects of correction
      of VDI on OCN and GluMet, and determined the associations of OCN with 25
      hydroxyvitamin D (25-OHD) and GluMet. DESIGN, PATIENTS AND MEASUREMENTS: This
      study involved 230 obese children in a cross-sectional part and 72 participants
      in a prospective part in which children with VDI were treated with vitamin D2 at
      a dose of 20 000 IU daily for 28 days. All 230 children underwent an oral glucose
      tolerance test and had their serum total and undercarboxylated OCNs and 25-OHD
      measured. Forty of 72 children were reassessed for the GluMet and serum total and
      undercarboxylated OCNs and 25-OHD after the vitamin D2 treatment. RESULTS: In the
      prospective part, correction of VDI by raising mean (SD) 25-OHD of 51.5 (12.3) to
      141.8 (40.8) nmol/l resulted in an improvement of their GluMet and increase in
      their whole-body insulin sensitivity index with no changes in their OCN measures.
      In the cross-sectional part, after adjustments for age, sex and puberty, the
      total (beta = 0.322) and undercarboxylated OCNs (beta = 0.315) were positively
      associated with insulinogenic index, which is an index of insulin secretion (P =
      0.034 and 0.037, respectively) in the group of prediabetic and diabetic children.
      CONCLUSIONS: Correction of VDI increased insulin sensitivity and improved GluMet,
      but had no effect on serum OCN measures. OCN was associated with increased
      insulin secretion in children with abnormal GluMet.

PMID- 24107002
TI  - Hair miR-29a levels are decreased in patients with scleroderma.
AB  - In the present study, we evaluated the possibility that we can utilize hair shaft
      miR-29a levels as disease marker of scleroderma. Hair samples were obtained from
      20 scleroderma patients, five dermatomyositis patients and 13 controls. microRNAs
      were purified from hairs as well as skins or sera, and miR-29a levels were
      measured with quantitative real-time polymerase chain reaction. Mean hair miR-29a
      levels in scleroderma patients were significantly lower than those in control
      subjects or dermatomyositis, while expression levels of hair shaft marker keratin
      34 were similar among them. There was no strong correlation among the miR-29a
      levels in the hair, skin and serum of each patient, suggesting that hair
      microRNAs can be independent biomarkers. We found scleroderma patients with
      decreased miR-29a levels had contracture of the phalanges at a significantly
      higher prevalence than those without. To confirm the clinical usefulness of hair
      microRNAs, large-scale researches are needed in the future. 

PMID- 24107005
TI  - Building up water-wire clusters: isomer-selective ultraviolet and infrared
      spectra of jet-cooled 2-aminopurine (H2O)n, n = 2 and 3.
AB  - 2-Aminopurine (2AP) is an adenine analogue with a high fluorescence quantum yield
      in water solution, which renders it a useful real-time probe of DNA structure. We
      report the ultraviolet (UV) and infrared (IR) spectra of size-selected and jet
      cooled 9H-2AP.(H2O)n clusters with n = 2 and 3. Mass- and species-specific UV/UV
      holeburning spectroscopy allows to separate the UV spectra of four cluster
      isomers in the 31,200-33,000 cm(-1) spectral region with electronic band origins
      at 31339, 31450, 31891, and 32163 cm(-1). Using IR/UV depletion spectroscopy in
      combination with B3LYP calculated harmonic vibrational frequencies, the H-bonding
      topologies of two isomers of the n = 2 and of two isomers of the n = 3 cluster
      are identified. One n = 2 isomer (denoted 2A) forms a water dimer chain between
      the N9H and N3 atoms at the sugar-edge site, the other isomer (denoted 2D) binds
      one H2O at the sugar-edge site and the other at the trans-amino site between the
      N1 atom and the NH2 group. For 2-aminopurine.(H2O)3, one isomer (denoted 3A)
      forms an H-bonded water wire at the sugar-edge site, while isomer 3B accommodates
      two H2O molecules at the sugar-edge and one at the trans-amino site. The
      approximate second-order coupled cluster (CC2) method predicts the adiabatic S1 <
      S0 transitions of 9H-2-aminopurine and six water cluster isomers with n = 1-3 in
      very good agreement with the experimental 0(0)(0) frequencies, with differences
      of <0.6%. The stabilization of the S1(pipi*) state of 2-aminopurine by water
      clusters is highly regiospecific: Isomers with one or two H2O molecules H-bonded
      in the trans-amino position induce large spectra red shifts, corresponding to
      1pipi* state stabilization of 10-12 kJ/mol, while water-wire cluster solvation at
      the sugar-edge leads to much smaller stabilization. The evolution of the IR
      spectra of the water-wire clusters with n = 1-3 that are H-bonded to the sugar
      edge site is discussed. Qualitatively different regions (denoted I to IV) can be
      attributed to the different free and H-bonded OH, NH, NH2 and OH...OH water-wire
      stretch vibrations.

PMID- 24107004
TI  - 2013 White Paper on recent issues in bioanalysis: 'hybrid'--the best of LBA and
      LCMS.
AB  - The 2013 7th Workshop on Recent Issues in Bioanalysis was held in Long Beach,
      California, USA, where close to 500 professionals from pharmaceutical and
      biopharmaceutical companies, CROs and regulatory agencies convened to discuss
      current topics of interest in bioanalysis. These 'hot' topics, which covered both
      small and large molecules, were the starting point for fruitful exchanges of
      knowledge, and sharing of ideas among speakers, panelists and attendees. The
      discussions led to specific recommendations pertinent to bioanalytical science.
      Such as the previous editions, this 2013 White Paper addresses important
      bioanalytical issues and provides practical answers to the topics presented,
      discussed and agreed upon by the global bioanalytical community attending the 7th
      Workshop on Recent Issues in Bioanalysis. 

PMID- 24107006
TI  - Measurement of blood protease kinetic parameters with self-assembled monolayer
      ligand binding assays and label-free MALDI-TOF MS.
AB  - We report novel ligand binding assay (LBA) surface modalities that permit plasma
      protease catalytic efficiency (kcat/km) determination by MALDI-TOF MS without the
      use of liquid chromatography or internal standards such as chemical or metalized
      labels. Two model LBAs were constructed on planar self-assembled monolayers
      (SAMs) and used to evaluate the clinically relevant metalloprotease ADAMTS-13
      kinetics in plasma. The SAM chemistries were designed to improve biosampling
      efficiency by minimization of nonspecific adsorption of abundant proteins present
      at ~100,000* the concentration of the endogenous enzyme. In the first protocol,
      in-solution digestion of the ADAMTS-13 substrate (vWFh) was performed with
      immunoaffinity enrichment of the reaction substrate and product to SAM arrays.
      The second configuration examined protease kcat/km via a surface digestion
      modality where different substrates were covalently immobilized to the SAM at
      controlled surface density for optimized protease screens. The results show the
      MALDI-TOF MS LBA platforms provide limits of quantitation to ~1% protease
      activity (~60 pM enzyme concentration) in <1 h analysis time, a ~16* improvement
      over other MS-based LBA formats. Implementation of a vacuum-sublimed MALDI matrix
      provided good MALDI-TOF MS intra- and interday repeatability, ~1.2 and ~6.6% RSD,
      respectively. Platform reliability permitted kcat/km determination without
      internal standards with observed values ~10* improved versus conventional
      fluorophoric assays. Application of the assays to 12 clinical plasma samples
      demonstrated proof-of-concept for clinical applications. Overall, this work
      demonstrates that rationally designed surface chemistries for MALDI-TOF MS may
      serve as an alternative, label-free methodology with potential for a wide range
      of biotechnology applications related to targeted enzyme molecular diagnostics.

PMID- 24107007
TI  - Kinetic and electrochemical studies of the oxidative addition of demanding
      organic halides to Pd(0): the efficiency of polyphosphane ligands in low
      palladium loading cross-couplings decrypted.
AB  - Oxidative addition (OA) of organic halides to palladium(0) species is a
      fundamental reaction step which initiates the C-C bond formation catalytic
      processes typical of Pd(0)/Pd(II) chemistry. The use of structurally congested
      polyphosphane ligands in palladium-catalyzed C-C bond formation has generated
      very high turnover numbers (TONs) in topical reactions such as Heck, Suzuki,
      Sonogashira couplings, and direct sp(2)C-H functionalization. Herein, the OA of
      aryl bromides to Pd(0) complexes stabilized by ferrocenylpolyphosphane ligands L1
      (tetraphosphane), L2 (triphosphane), and L3 (diphosphane) is considered. The
      investigation of kinetic constants for the addition of Ph-Br to Pd(0)
      intermediates (generated by electrochemical reduction of Pd(II) complexes
      coordinated by L1-L3) is reported. Thus, in the OA of halides to the Pd(0)
      complex coordinated by L1 the series of rate constants kapp is found (mol(-1) L
      s(-1)): kapp(Ph-Br) = 0.48 > kapp(ClCH2-Cl) = 0.25 ? kapp(p-MeC6H4-Br) = 0.08 ~
      kapp(o-MeC6H4-Br) = 0.07 ? kapp(Ph-Cl). Kinetic measurements clarify the
      influence that the presence of four, three, or two phosphorus atoms in the
      coordination sphere of Pd has on OA. The presence of supplementary phosphorus
      atoms in L1 and L2 unambiguously stabilizes Pd(0) species and thus slows down the
      OA of Ph-Br to Pd(0) of about 2 orders of magnitude compared to the diphosphane
      L3. The electrosynthesis of the complexes resulting from the OA of organic
      halides to [Pd(0)/L] is easily performed and show the concurrent OA to Pd(0) of
      the sp(3)C-Cl bond of dichloromethane solvent. The resulting unstable Pd/alkyl
      complex is characterized by NMR and single crystal X-ray structure. We
      additionally observed the perfect stereoselectivity of the OA reactions which is
      induced by the tetraphosphane ligand L1. Altogether, a clearer picture of the
      general effects of congested polydentate ligands on the OA of organic halides to
      Pd(0) is given. 

PMID- 24107008
TI  - Undernutrition among HIV positive women in Humera hospital, Tigray, Ethiopia,
      2013: antiretroviral therapy alone is not enough, cross sectional study.
AB  - BACKGROUND: In Ethiopia, undernutrition among women on antiretroviral therapy has
      been a major challenge to achieve the full impact of intervention. Twenty seven
      percent and 17% of reproductive age Ethiopian women are chronically malnourished
      and anemic, respectively. Most studies to examine risk factors have been limited
      to the general population and ART-naive HIV-positive women, making it difficult
      to generalize findings to ART-treated HIV-positive women. The objectives of this
      study were thus to assess nutritional status and associated factors among adult
      women (>= 20 years) on antiretroviral therapy. METHODS: From August to September
      we conducted an Institution based cross-sectional survey among 276 women on
      antiretroviral therapy in Humera Hospital, Tigray, Ethiopia. Data was collected
      using structured and standard face to face interview, anthropometric
      measurements, BD FACS (CD4 count machine) and Sysmex-21 (hemoglobin analyzer).
      Logistic regression was done using SPSS version 16 to identify factors that are
      associated with nutritional status. RESULTS: The prevalence of under nutrition
      (Body mass index < 18.5 kg/m(2)) Was 42.3% (95% CI: 37.4% - 47.3%). Severe,
      moderate and mild under nutrition was detected on 12%, 10% and 20.3% respondents,
      respectively. The prevalence of wasting (percentage body weight loss >5%) was 75%
      (95% CI: 70.4% - 79.2%). Severe wasting was accounted for 26.9% of respondents.In
      the multivariate analysis, Household food insecurity [AOR = 1.85; 95%CI 1.16,
      2.86], inadequate dietary diversity [AOR = 1.19; 95%CI 1.08, 1.75], anemia [AOR =
      1.67; 95%CI 1.05, 2.65] and absence of nutritional support [AOR = 0.34 95%CI
      0.22, 0.54) were found to be independent predictors of under-nutrition.
      CONCLUSION: HIV/AIDS is associated with an increased burden of undernutrition
      even among ART treated women in Humera Hospital, Tigray, Ethiopia. In addition to
      ART among HIV positive women interventions to ameliorate poor nutritional status
      may be necessary in this and similar settings. Such interventions aimed at
      improving household food security, dietary diversity, micronutrient
      supplementation, proper use of therapeutic food, as well as treating oral
      candidiasis.

PMID- 24107010
TI  - Patient care pathways under the model of integrating tuberculosis service with
      general hospitals in China.
AB  - OBJECTIVE: To report care pathways of tuberculosis (TB) patients under the
      integrated model, where TB clinical service is provided by a general hospital
      instead of the TB dispensary, with the aim of providing policy recommendations
      for TB care reforms in China. METHODS: Six counties implementing the integrated
      model were randomly selected, and 50 TB patients in each county participated in a
      questionnaire survey. RESULTS: Of the 301 participants, 82 visited only the TB
      designated hospital. A patient visited a median of two health providers in total.
      The median external provider delay and internal provider delay were 1 and 0 day,
      respectively. The median out-of-pocket medical costs were US$379 in total; US$293
      in the TB units and US$0 in other health units in the TB designated hospital.
      Logistic regression analyses suggested that patients who visited the primary care
      facilities first tended to have longer external delays (OR = 5.71) than patients
      who visited the other hospitals (OR = 10.16). CONCLUSION: The integrated model is
      promising as it reported relatively fewer patient pathways and shorter delays
      than the dispensary model. However, the integrated model did not reduce patient
      out-of-pocket costs.

PMID- 24107011
TI  - Hydraulically controlled discrete sampling from open boreholes.
AB  - Groundwater sampling from open boreholes in fractured-rock aquifers is
      particularly challenging because of mixing and dilution of fluid within the
      borehole from multiple fractures. This note presents an alternative to
      traditional sampling in open boreholes with packer assemblies. The alternative
      system called ZONFLO (zonal flow) is based on hydraulic control of borehole flow
      conditions. Fluid from discrete fractures zones are hydraulically isolated
      allowing for the collection of representative samples. In rough-faced open
      boreholes and formations with less competent rock, hydraulic containment may
      offer an attractive alternative to physical containment with packers. Preliminary
      test results indicate a discrete zone can be effectively hydraulically isolated
      from other zones within a borehole for the purpose of groundwater sampling using
      this new method. 

PMID- 24107009
TI  - Societal costs of non-cardiac chest pain compared with ischemic heart disease--a
      longitudinal study.
AB  - BACKGROUND: Non-cardiac chest pain (NCCP) is a common complaint. Our aim was to
      present a detailed description of the costs of patients with NCCP compared to
      patients with acute myocardial infarction (AMI) and Angina Pectoris (AP) from a
      societal perspective. METHODS: Data on healthcare utilization and annual societal
      costs, including direct healthcare costs and indirect costs due to productivity
      loss, were collected from different databases. The participants consisted of 199
      patients from a general hospital in Sweden (99 with NCCP, 51 with AMI, 49 with
      AP), mean age of 67 years, 59% men. RESULTS: NCCP, AMI, and AP patients had on
      average 54, 50 and 65 primary care contacts and 3, 4, and 4 hospital admissions
      during a period of 2 years. Length of hospital stay was 6, 11 and 11 days. On
      average, 14%, 18%, and 25% of NCCP, AMI and AP patients were on sick-leave
      annually, and about 12% in each group received a disability pension. The mean
      annual societal costs of NCCP, AMI and AP patients were ?10,068, ?15,989 and
      ?14,737. CONCLUSIONS: Although the annual societal cost of NCCP patients was
      lower than in AMI and AP patients, the cost was still considerable (?10,068).
      Taken into account the high prevalence of NCCP, the cumulative annual national
      cost of these patients could be more than the double of AMI and AP if all
      patients incurred the same costs as in this study. Targeted interventions are
      important in order to support patients with NCCP and minimize healthcare
      utilization and costs.

PMID- 24107012
TI  - Development of glycosylation using the glucopyranose 1,2-orthobenzoate under
      electrochemical conditions.
AB  - Substituted glucopyranose 1,2-orthobenzoate undergoes beta-selective
      glycosylation. The developed orthobenzoate derivative was stable under standard
      workup conditions and efficiently provided a variety of glycosides by EGA
      (electrogenerated acid), produced by anodic oxidation of cyclohexanol. Upon
      comparison with Lewis and Bronsted acids, EGA superiorly affected activation of
      the orthoester to afford desired glycosides possessing such aglycons as sugars,
      steroids, and adamantanes. 

PMID- 24107013
TI  - Ministers should keep out of the pay review process.

PMID- 24107014
TI  - Older nurses fearful of physical toll as later retirement age looms.

PMID- 24107015
TI  - RCN members to vote on change in how subscriptions are set.

PMID- 24107019
TI  - Court ruling reveals the NMC has been acting outside of its powers.

PMID- 24107024
TI  - 'Food and drink should be put on a par with medicine in hospitals'.

PMID- 24107025
TI  - UK governments use 'intimidation tactics' to curb pay rises for nurses.

PMID- 24107028
TI  - Seven-day GP service would require significant extra funding.

PMID- 24107030
TI  - Work-life imbalance and the pressures that are making nurses sick.

PMID- 24107036
TI  - Familial hypercholesterolaemia.

PMID- 24107037
TI  - A nursing alternative to prison.
AB  - There are 100 liaison and diversion teams in England working to ensure offenders
      with mental health needs are treated and steered away from the criminal justice
      system when appropriate. The teams which include nurses, also have a role in
      reducing re-offending rates.

PMID- 24107038
TI  - Award highlighted our specialty.
AB  - Stacey Atkinson was named nurse of the year in 2002 in recognition of her
      pioneering work providing sex education to young people with learning
      disabilities. The award raised the profile of learning disability nursing and
      boosted Ms Atkinson's teaching career.

PMID- 24107039
TI  - Joined-up thinking.
AB  - In 2001 the Department of Health instructed NHS trusts to develop networks to
      support black and minority ethnic staff. Since then networks have fallen out of
      favour and may have folded. Supporters argue that trusts neglect networks at
      their peril- they are an in valuable source of intelligence about what is
      happening to front line staff and patients.

PMID- 24107040
TI  - Making time to care.
AB  - As its name suggests, the Releasing Time to Care project in Scotland aims to
      eliminate inefficiency and to redirect time and resources to areas where they are
      most needed. The new way of working is yielding other benefits too, including
      improved staff morale and lower absence rates.

PMID- 24107052
TI  - NHS England is a strange creature - a conjoined body with two heads.

PMID- 24107053
TI  - Let's make it easier for patients to identify nurses.

PMID- 24107054
TI  - Embrace new technology, but first acknowledge its effect.

PMID- 24107058
TI  - Private health insurer ordered to stop misleading marketing.

PMID- 24107057
TI  - Vegetarians need more choice of vaccines and medications.

PMID- 24107059
TI  - What motivated supermarket giants to mock mental illness?

PMID- 24107061
TI  - Introducing intentional rounding: a pilot project.
AB  - AIM: To report on the introduction of intentional rounding in an NHS trust.
      METHOD: A two-stage pilot project with participatory methods underpinned by core
      practice development principles was undertaken to introduce intentional rounding.
      FINDINGS: Patients and staff found intentional rounding to be a positive
      experience, although nurses and midwives felt they were inadequately prepared to
      implement the practice. Leaders and managers who engaged in learning
      opportunities before the pilot study tended to achieve more successful and
      sustained practice change. CONCLUSION: There is disagreement among nurses about
      the contribution of intentional rounding to patient care, particularly in light
      of the weak evidence base, time involved and associated documentation. Therefore,
      further research is needed in this area.

PMID- 24107062
TI  - Antimicrobial stewardship: the role of the nurse.
AB  - Infections caused by organisms resistant to multiple drugs are associated with
      morbidity and mortality, prolonged hospital stay and increased costs. Since
      antibiotic use is the main factor in the development of resistance, it is hoped
      that the judicious use of antibiotics will reduce the emergence of antimicrobial
      resistance. This article addresses antibiotic misuse in the inpatient setting and
      outlines the role of the nurse in optimising antibiotic therapy through
      antimicrobial stewardship. 

PMID- 24107063
TI  - Intravenous therapy in older patients.
AB  - Intravenous therapy is available in a variety of settings and for patients of all
      ages. Therefore, it is essential that nurses have the clinical knowledge and
      technical expertise to carry out this procedure and care for patients,
      particularly those who are vulnerable, such as older people. This article
      provides an overview of the anatomy and physiology of the skin and veins.
      Considerations for improving venous access, selection and insertion of a
      peripheral cannula, and recognition, prevention and management of complications
      in older people are discussed. Alternative routes for the administration of
      fluids and medications are also explored. 

PMID- 24107064
TI  - Portal hypertension.

PMID- 24107067
TI  - Working out where it hurts.

PMID- 24107065
TI  - Exercise for the brain.

PMID- 24107069
TI  - Multimodal ultrasound-photoacoustic imaging of tissue engineering scaffolds and
      blood oxygen saturation in and around the scaffolds.
AB  - Preclinical, noninvasive imaging of tissue engineering polymeric scaffold
      structure and/or the physiological processes such as blood oxygenation remains a
      challenge. In vitro or ex vivo, the widely used scaffold characterization
      modalities such as porosimetry, electron or optical microscopy, and X-ray
      microcomputed tomography have limitations or disadvantages-some are invasive or
      destructive, others have limited tissue penetration (few hundred micrometers)
      and/or show poor contrast under physiological conditions. Postmortem histological
      analysis, the most robust technique for the evaluation of neovascularization is
      obviously not appropriate for acquiring physiological or longitudinal data. In
      this study, we have explored the potential of ultrasound (US)-coregistered
      photoacoustic (PA) imaging as a noninvasive multimodal imaging modality to
      overcome some of the above challenges and/or provide complementary information.
      US-PA imaging was employed to characterize poly(lactic-co-glycolic acid) (PLGA)
      polymer scaffolds or single-walled carbon nanotube (SWCNT)-incorporated PLGA
      (SWCNT-PLGA) polymer scaffolds as well as blood oxygen saturation within and
      around the scaffolds. Ex vivo, PLGA and SWCNT-PLGA scaffolds were placed at 0.5,
      2, and 6 mm depths in chicken breast tissues. PLGA scaffolds could be localized
      with US imaging, but generate no PA signal (excitation wavelengths 680 and 780
      nm). SWCNT-PLGA scaffolds generated strong PA signals at both wavelengths due to
      the presence of the SWCNTs and could be localized with both US and PA imaging
      depths between 0.5-6 mm (lateral resolution = 90 MUm, axial resolution = 40 MUm).
      In vivo, PLGA and SWCNT-PLGA scaffolds were implanted in subcutaneous pockets at
      2 mm depth in rats, and imaged at 7 and 14 days postsurgery. The anatomical
      position of both the scaffolds could be determined from the US images. Only SWCNT
      PLGA scaffolds could be easily detected in the US-PA images. SWCNT-PLGA scaffolds
      had significant four times higher PA signal intensity compared with the
      surrounding tissue and PLGA scaffolds. In vivo blood oxygen saturation maps
      around and within the PLGA scaffolds could be obtained by PA imaging. There was
      no significant difference in oxygen saturation for the PLGA scaffolds at the two
      time points. The blood oxygen saturation maps complemented the histological
      analysis of neovascularization of the PLGA scaffolds.

PMID- 24107070
TI  - Bifunctional iminophosphorane organocatalysts for enantioselective synthesis:
      application to the ketimine nitro-Mannich reaction.
AB  - The design, synthesis, and development of a new class of modular, strongly basic,
      and tunable bifunctional Bronsted base/H-bond-donor organocatalysts are reported.
      These catalysts incorporate a triaryliminophosphorane as the Bronsted basic
      moiety and are readily synthesized via a last step Staudinger reaction of a
      chiral organoazide and a triarylphosphine. Their application to the first general
      enantioselective organocatalytic nitro-Mannich reaction of nitromethane to
      unactivated ketone-derived imines allows the enantioselective construction of
      beta-nitroamines possessing a fully substituted carbon atom. The reaction is
      amenable to multigram scale-up, and the products are useful for the synthesis of
      enantiopure 1,2-diamine and alpha-amino acid derivatives.

PMID- 24107071
TI  - Evaluation of oxidative status with exhaled breath 8-isoprostane levels in
      patients with hyperthyroidism.
AB  - INTRODUCTION: Studies conducted so far on the effect of hyperthyroidism on
      oxidative stress (OS) have employed blood and urine samples. Exhaled Breath
      Condensate (EBC) is a non-invasive technique used to take sample from lungs to
      determine many biological indications. The aim of the present study was determine
      the possibility of using 8- isoprostane levels in EBC as an indicator of OS in
      hyperthyroid patients. METHODS: The present study was performed on 42 patients
      with hyperthyroidism and 42 healthy control subjects. Hyperthyroid patients
      included patients with newly diagnosed Graves' disease, toxic multinodular goiter
      and toxic adenoma. Exhaled breath condensates were collected from patients in
      each group using a condensing device. 8- isoprostane levels as an indicator of OS
      in EBC were detected via immunoassay method. RESULTS: Hyperthyroid patients and
      control groups had 8-isoprostane levels of 6.08+/-6.31 and 1.56+/-0.88 pg/ml,
      respectively. The difference between patient and control groups was statistically
      significant (p<0.001). Of the hyperthyroid patients, eleven had Graves', 21
      multinodular goiter, and 10 toxic adenoma diagnosis. There were no significant
      differences among patients of different diagnoses for 8-isoprostane levels
      (p=0.541). No significant correlations were found between 8-isoprostane and free
      thyroxine (fT4) or thyroid stimulating hormone (TSH) levels. CONCLUSION: In the
      present study, 8-isoprostane levels in EBC of hyperthyroid patients were found to
      be significantly higher than that in healthy control group. This study is
      important in that it is the first to evaluate the effects on respiratory system
      of elevated OS of hyperthyroidism in EBC.

PMID- 24107073
TI  - Gene therapy: pursuing restoration of dermal adhesion in recessive dystrophic
      epidermolysis bullosa.
AB  - The replacement of a defective gene with a fully functional copy is the goal of
      the most basic gene therapy. Recessive dystrophic epidermolysis bullosa (RDEB) is
      characterised by a lack of adhesion of the epidermis to the dermis. It is an
      ideal target for gene therapy as all variants of hereditary RDEB are caused by
      mutations in a single gene, COL7A1, coding for type VII collagen, a key component
      of anchoring fibrils that secure attachment of the epidermis to the dermis. RDEB
      is one of the most severe variants in the epidermolysis bullosa (EB) group of
      heritable skin diseases. Epidermolysis bullosa is defined by chronic fragility
      and blistering of the skin and mucous membranes due to mutations in the genes
      responsible for production of the basement membrane proteins. This condition has
      a high personal, medical and socio-economic impact. People with RDEB require a
      broad spectrum of medications and specialised care. Due to this being a systemic
      condition, most research focus is in the area of gene therapy. Recently,
      preclinical works have begun to show promise. They focus on the virally mediated
      ex vivo correction of autologous epithelium. These corrected cells are then to be
      expanded and grafted onto the patient following the lead of the first successful
      gene therapy in dermatology being a grafting of corrected tissue for junctional
      EB treatment. Current progress, outstanding challenges and future directions in
      translating these approaches in clinics are reviewed in this article. 

PMID- 24107074
TI  - Heparin decamer bridges a growth factor and an oligolysine by different charge
      driven interactions.
AB  - Full-length heparin is widely used in tissue engineering applications due its
      multiple protein-binding sites that allow it to retain growth factor affinity
      while associating with oligopeptide components of the tissue scaffold. However,
      the extent to which oligopeptide coupling interferes with cognate protein binding
      is difficult to predict. To investigate such simultaneous interactions, we
      examined a well-defined ternary system comprised of acidic fibroblast growth
      factor (FGF), tetralysine (K4), with a heparin decamer (dp10) acting as a
      noncovalent coupler. Electrospray ionization mass spectrometry was used to assess
      binding affinities and complex stoichiometries as a function of ionic strength
      for dp10.K4 and FGF.dp10. The ionic strength dependence of K4.dp10 formation is
      qualitatively consistent with binding driven by the release of condensed
      counterions previously suggested for native heparin with divalent oligopeptides
      (Mascotti, D. P.; Lohman, T. M. Biochemistry 1995, 34, 2908-2915). On the other
      hand, FGF binding displays more complex ionic strength dependence, with higher
      salt resistance. Remarkably, dp10 that can bind two FGF molecules can only bind
      one tetralysine. The limited binding of K4 to dp10 suggests that the tetralysine
      might not block growth factor binding, and the 1:1:1 ternary complex is indeed
      observed. The analysis of mass distribution of the bound dp10 chains in FGF.dp10,
      FGF2.dp10, and FGF.dp10.K4 complexes indicated that higher degrees of dp10
      sulfation promote the formation of FGF2.dp10 and FGF.dp10.K4. Thus, the
      selectivity of appropriately chosen short heparin chains could be used to
      modulate growth factor sequestration and release in a way not feasible with
      heterogeneous native heparin. In support of this, human hepatocellular carcinoma
      cells (HEP3Bs) treated with FGF.dp10.K4 were found to exhibit biological activity
      similar to cells treated with FGF. 

PMID- 24107072
TI  - A double-blind, randomized, placebo-controlled study to assess the safety,
      antiviral activity and pharmacokinetics of GSK2336805 when given as monotherapy
      and in combination with peginterferon alfa-2a and ribavirin in hepatitis C virus
      genotype 1-infected treatment-naive subjects.
AB  - BACKGROUND & AIMS: GSK2336805 is a HCV NS5A inhibitor for chronic hepatitis C
      (CHC). In a prior Phase I study, GSK2336805 was well tolerated and had an
      antiviral and pharmacokinetic profile suitable for once-daily administration.
      This 28-day, double-blind, randomized, placebo-controlled study evaluated once
      daily GSK2336805 60 mg alone or in combination with peginterferon alfa-2a (180
      MUg per week) and ribavirin (1000-1200 mg daily) (PEG/RIBA) in treatment-naive
      genotype 1 CHC subjects. METHODS: Five centres enrolled 16 subjects in the USA
      and Puerto Rico who received GSK2336805 + PEG/RIBA or placebo + PEG/RIBA.
      RESULTS: Following a single monotherapy dose of GSK2336805 on day 1, median
      reduction from baseline in HCV RNA was -2.96 log10 (N = 11) vs. -0.13 log10 (N =
      4) for placebo. With the addition of PEG/RIBA on day 2, subjects receiving
      GSK2336805 exhibited greater decreases in viral load over the 28-day treatment
      period as compared with placebo. At day 28, median reduction from baseline was 
      4.86 log10 (N = 9) in the GSK2336805 + PEG/RIBA group as compared with -1.98
      log10 (N = 4) in the placebo + PEG/RIBA group. At day 28, rapid virological
      response (RVR) occurred in 8/11 (73%) of the GSK2336805 + PEG/RIBA subjects as
      compared with 1/4 (25%) of the placebo + PEG/RIBA subjects. Adverse events were
      consistent with those reported in clinical trials of peginterferon and ribavirin,
      and no unique adverse events appeared to be associated with GSK2336805.
      CONCLUSIONS: GSK2336805 is a potent NS5A inhibitor that showed a substantial
      antiviral effect as a monotherapy and in combination with peginterferon and
      ribavirin. ClinicalTrials.gov Identifier: NCT01439373.

PMID- 24107075
TI  - Synthesis, characterization and pH-controllable methotrexate release from
      biocompatible polymer/silica nanocomposite for anticancer drug delivery.
AB  - The objective of this study was to develop pH-responsive silica nanoparticles by
      imidazole-based ionic liquid for controlled release of methotrexate. In this
      article, we synthesized pH-responsive cationic silica nanoparticles by graft
      copolymerization of vinyl functionalized silica nanoparticles and methacrylic
      acid (MAA) monomer. Imidazole-based ionic liquid (Im-IL) was verified by (1)HNMR
      and Fourier-transform infrared (FTIR) spectroscopy. The synthesized
      functionalized silica particles were characterized and confirmed by various
      technologies including the scanning electron microscopy (SEM), the infrared
      spectroscopy (IR) and the thermogravimetric analysis (TGA). SEM results reveal
      the uniformity in size/shape of silica particles. This nanosystem is modified for
      targeted delivery of an anticancer agent methotrexate. The nanocomposite-MTX
      complex was formed at physiological pH (7.4) due to the electrostatic
      interactions between anionic carboxylic group of MTX molecules and cationic rings
      in carrier, while, the release of which can be achieved through the cleavage of
      the nanocomposite-MTX complex by protonation of carboxyl groups in the MTX
      segment that are sensitive to variations in external pH at weak acidic
      conditions. FT-IR spectroscopy showed the presence of light interactions between
      the silicate silanols and the drug. MCF7 cells were incubated with the MTX-free
      nanocomposite and MTX-loaded nanocomposite at various concentrations for 24, 48
      and 72 h, and the data showed that the nanocomposites themselves did not affect
      the growth of MCF7 cells. Antitumor activity of the MTX-loaded nanocomposites
      against the cells was kept over the whole experiment process. The results showed
      that the MTX could be released from the fibers without losing cytotoxicity.

PMID- 24107077
TI  - Commentary for virtual issue on concept analysis.

PMID- 24107076
TI  - Association of interleukin-33 gene single nucleotide polymorphisms with ischemic
      stroke in north Chinese population.
AB  - BACKGROUND: IL-33, an IL-1-like cytokine, is a ligand for IL1RL1, which is an
      important effector molecule of type 2 T helper responses. Although IL-33/IL1RL1
      interaction has been suggested to be important in the development of
      atherosclerosis, genetic influences of the polymorphisms of IL33 in human
      ischemic stroke are unclear. The aim of this study was to examine whether the
      single nucleotide polymorphisms in IL33 are associated with ischemic stroke in
      Northern Chinese population. METHODS: We used a nested case-control study
      involving 90 ischemic stroke patients and 270 age-matched, sex-matched and blood
      pressure-matched non-ischemic stroke controls from a rural population and
      determined the genotypes of four polymorphisms (rs1929992, rs10975519, rs4742170,
      rs16924159) in IL33 by Snapshot SNP genotyping assays to assess any links with
      ischemic stroke. RESULTS: Univariate analysis showed two single nucleotide
      polymorphisms (rs1929992, rs4742170) in IL33 were associated with ischemic stroke
      in additive, dominant, and recessive model. Binary Logistic Regression shows that
      rs4742170 variation is the most important factor associated with ischemic stroke
      (adjusted odds ratio (OR) = 1.880, 95% confidence interval (CI) = 1.316-2.686 in
      an additive model; OR = 2.091, CI = 1.249-3.498 in a dominant model; OR = 2.623,
      CI = 1.366-5.036 in a recessive model). CONCLUSION: In this sample of patients,
      genetic variation of rs4742170 in IL33 is significantly associated with the
      developing of ischemic stroke.

PMID- 24107078
TI  - Factors associated with bicycle-helmet use among 8-16 years aged Turkish
      children: a questionnaire survey.
AB  - The purpose of this cross-sectional, descriptive study was to assess the rates of
      helmet and to examine variables related to bicycle helmet use in a sample of 8-16
      year old Turkish children. Data were collected from a purposive sample of 1180
      students who self-identified as cyclists and 1128 parents or guardians in two
      state primary schools in two urban municipalities in the northern part of
      Istanbul, Turkey. Results showed that self-reported helmet use was found
      prevalent in 4.4% of the children. The most cited reasons for not wearing a
      helmet were: 'don't own one', 'helmets are uncool', and 'uncomfortable'.
      Significant differences between helmet users and non-users correlated to gender,
      age, owning a bicycle helmet, wearing a friend's bicycle helmet and parents or
      guardian's bicycle helmet use while riding. Only three variables--helmet
      ownership (OR = 10.028, 95% CI 5.08, 19.79), parents' helmet use (OR = 2.62, 95%
      CI 1.22, 5.66) and friends' helmet use (OR = 0.16, 95% CI 0.07, 0.37) emerged as
      significant predictors of the likelihood of helmet use. The relatively low helmet
      use prevalence points to an urgent need for a multipronged campaign, including
      strategies such as raising awareness, educating primarly parents and friends, and
      distributing bicycle helmets for free or at a reduced cost.

PMID- 24107079
TI  - Author inflation masks global capacity for species discovery in flowering plants.
AB  - Species discovery is a fundamental first step for all of biodiversity science.
      Recent research has claimed that the increasing number of authors associated with
      the description of new species represents an expanding workforce discovering the
      remaining new species from an ever-diminishing pool. Here, we present a
      comprehensive dataset from The International Plant Names Index (IPNI) of new
      species of flowering plant published between 1970 and 2011. We show that, on
      average, 1855 new species have been described annually since 1970. We show that
      compared to other scientific disciplines the increased number of authors on
      taxonomic papers is relatively small and may reflect changes in scientific
      practice rather than an increase in taxonomic capacity. These data, alongside
      published results demonstrating a lag period of 35 yr between a specimen being
      collected and published as a new species, strongly suggest that the global
      taxonomic capacity to describe new species of flowering plant is stagnant at a
      time of unprecedented concern for conservation and extinction.

PMID- 24107080
TI  - The expression and significance of TIPE2 in peripheral blood mononuclear cells
      from asthmatic children.
AB  - Tumour necrosis factor-alpha-induced protein-8 like-2 (TIPE2) is a newly
      identified immune negative regulator. The abnormal expression of TIPE2 has been
      found in several human inflammatory diseases. However, the expression level and
      clinical significance of TIPE2 in childhood asthma remain unclear. In this study,
      we detected TIPE2 expression in peripheral blood mononuclear cells (PBMC) from 42
      children with asthma and 39 healthy controls by RT-PCR, qRT-PCR and Western blot.
      We also detected the levels of serum total immunoglobulin E (IgE), eosinophil
      (EO), interleukin-4 (IL-4) and interferon-gamma (IFN-gamma) and analysed the
      correlations of TIPE2 expression with IgE, EO, IL-4 and IFN-gamma. The results
      showed that TIPE2 mRNA and protein expression were decreased in children with
      asthma compared with healthy controls. The levels of IgE, EO and IL-4 in the
      children with asthma were obviously higher than those in normal controls, while
      the level of IFN-gamma in patients with asthma was significantly lower than that
      in healthy subjects. Furthermore, the expression level of TIPE2 mRNA was
      negatively correlated with IgE, EO and IL-4. However, no statistically
      significant correlation was found between TIPE2 mRNA expression and serum IFN
      gamma level. In conclusion, our data suggest that reduced TIPE2 expression may
      contribute to the pathogenesis of childhood asthma. 

PMID- 24107081
TI  - Methyl-thiazoles: a novel mode of inhibition with the potential to develop novel
      inhibitors targeting InhA in Mycobacterium tuberculosis.
AB  - InhA is a well validated Mycobacterium tuberculosis (Mtb) target as evidenced by
      the clinical success of isoniazid. Translating enzyme inhibition to bacterial
      cidality by targeting the fatty acid substrate site of InhA remains a daunting
      challenge. The recent disclosure of a methyl-thiazole series demonstrates that
      bacterial cidality can be achieved with potent enzyme inhibition and appropriate
      physicochemical properties. In this study, we report the molecular mode of action
      of a lead methyl-thiazole, along with analogues with improved CYP inhibition
      profile. We have identified a novel mechanism of InhA inhibition characterized by
      a hitherto unreported "Y158-out" inhibitor-bound conformation of the protein that
      accommodates a neutrally charged "warhead". An additional novel hydrophilic
      interaction with protein residue M98 allows the incorporation of favorable
      physicochemical properties for cellular activity. Notably, the methyl-thiazole
      prefers the NADH-bound form of the enzyme with a Kd of ~13.7 nM, as against the
      NAD(+)-bound form of the enzyme.

PMID- 24107082
TI  - Crystalline GaSb nanowires synthesized on amorphous substrates: from the
      formation mechanism to p-channel transistor applications.
AB  - In recent years, because of the narrow direct bandgap and outstanding carrier
      mobility, GaSb nanowires (NWs) have been extensively explored for various
      electronics and optoelectronics. Importantly, these p-channel nanowires can be
      potentially integrated with n-type InSb, InAs, or InGaAs NW devices via different
      NW transfer techniques to facilitate the III-V CMOS technology. However, until
      now, there have been very few works focusing on the electronic transport
      properties of GaSb NWs. Here, we successfully demonstrate the synthesis of
      crystalline, stoichiometric, and dense GaSb NWs on amorphous substrates, instead
      of the commonly used III-V crystalline substrates, InAs, or GaAs NW stems as
      others reported. The obtained NWs are found to grow via the VLS mechanism with a
      narrow distribution of diameter (220 +/- 50 nm) uniformly along the entire NW
      length (>10 MUm) with minimal tapering and surface coating. Notably, when
      configured into FETs, the NWs exhibit respectable electrical characteristics with
      the peak hole mobility of ~30 cm(2) V(-1) s(-1) and free hole concentration of
      ~9.7 * 10(17) cm(-3). All these have illustrated the promising potency of such
      NWs directly grown on amorphous substrates for various technological
      applications, as compared with the conventional MOCVD-grown GaSb NWs.

PMID- 24107084
TI  - Crystal growth of new hexahydroxometallates using a hydroflux.
AB  - A series of seven compounds, Sr2Mn(OH)6, Ba2Mn(OH)6, Sr2Co(OH)6, Ba2Co(OH)6,
      Sr2Ni(OH)6, Ba2Ni(OH)6, and Ba2Cu(OH)6, were synthesized using a low-melting
      hydroflux, a hybrid approach between aqueous hydrothermal and molten hydroxide
      flux techniques. Crystals of the hexahydroxometallates were obtained by
      dissolving appropriate amounts of alkaline-earth nitrates or hydroxides and
      transition-metal oxides, acetates, or chlorides in the hydroflux and reacting at
      180-230  degrees C. The isostructural compounds all crystallize in the monoclinic
      space group P2(1/n). The monoclinic structure consists of isolated transition
      metal octahedra within a three-dimensional framework of corner- and edge-shared
      eight-coordinate, alkaline-earth polyhedra. Magnetic susceptibility data show
      that all compounds are simple paramagnets. Thermogravimetric analysis indicates
      that these hydroxides lose water between 215 and 350  degrees C and transform
      into oxide products, the identity of which depends on the metal cations present
      in the parent hexahydroxometallates.

PMID- 24107085
TI  - Intention to use condom among students in Agena preparatory school, Guraghe Zone,
      Ethiopia: with the application of health believe model.
AB  - BACKGROUND: HIV/AIDS is affecting the majority of the population, particularly
      the productive age group between 15-49 years resulting in social and economic
      crisis. The rate of HIV infection would undoubtedly be lowered if safe sexual
      practices such as correct and consistent use of condoms had been followed. The
      aim of this study was therefore to assess intention to use condom among students
      in Agena preparatory school, Guraghe zone, Ethiopia. Agena is an urban area in
      south Ethiopia. METHODS: Institution based cross-sectional study was conducted. A
      two stage sampling was applied by stratifying students in to (grade 11 and 12)
      with each grade having four section (A, B, C, D). Then systematic random sampling
      was used to select students in each section. Analyses of frequencies and summary
      measures like mean and Standard Deviation of selected variables were done.
      Bivariate and multivariate analysis was done to measure the association between
      different variables. RESULTS: Out of 450 respondents 122(27.1%) had history of
      sexual intercourse. Of whom the majority 86(70.5%) had two or more sexual
      partners. And 45(37%) never used condom, 12(9.8%) used condom sometimes and
      65(53.2%) used condom every time during sex. About 300(67.7%) of the respondents
      have no intention to use condom in the next sexual encounter. On multivariate
      analysis those students who have high perceived susceptibility (AOR = 1.94 (1.16
      3.2)) and high self-efficacy (AOR = 27 (14.4-54.2)) were more likely to have
      intention to use condom than others. CONCLUSIONS: Intention to use condom in the
      next sexual intercourse is very low. Information Education and Communication
      (IEC) on reducing number of sexual partners along with condom use promotion
      targeting in-school adolescents should be the primary strategy of HIV/AIDS
      prevention process.

PMID- 24107083
TI  - Children's Healthy Living (CHL) Program for remote underserved minority
      populations in the Pacific region: rationale and design of a community randomized
      trial to prevent early childhood obesity.
AB  - BACKGROUND: Although surveillance data are limited in the US Affiliated Pacific,
      Alaska, and Hawaii, existing data suggest that the prevalence of childhood
      obesity is similar to or in excess of other minority groups in the contiguous US.
      Strategies for addressing the childhood obesity epidemic in the region support
      the use of community-based, environmentally targeted interventions. The
      Children's Healthy Living Program is a partnership formed across institutions in
      the US Affiliated Pacific, Alaska, and Hawaii to design a community randomized
      environmental intervention trial and a prevalence survey to address childhood
      obesity in the region through affecting the food and physical activity
      environment. METHODS/DESIGN: The Children's Healthy Living Program community
      randomized trial is an environmental intervention trial in four matched-pair
      communities in American Samoa, the Commonwealth of the Northern Mariana Islands,
      Guam, and Hawaii and two matched-pair communities in Alaska. A cross-sectional
      sample of children (goal n = 180) in each of the intervention trial communities
      is being assessed for outcomes at baseline and at 24 months (18 months post
      intervention). In addition to the collection of the participant-based measures of
      anthropometry, diet, physical activity, sleep and acanthosis nigricans, community
      assessments are also being conducted in intervention trial communities. The
      Freely Associated States of Micronesia (Federated States of Micronesia, and
      Republics of Marshall Islands and Palau) is only conducting elements of the
      Children's Healthy Living Program sampling framework and similar measurements to
      provide prevalence data. In addition, anthropometry information will be collected
      for two additional communities in each of the 5 intervention jurisdictions to be
      included in the prevalence survey. The effectiveness of the environmental
      intervention trial is being assessed based on the RE-AIM (reach, effectiveness,
      adoption, implementation, maintenance) framework. DISCUSSION: The Children's
      Healthy Living Program environmental trial is designed to focus on capacity
      building and to maximize the likelihood of sustainable impact on childhood
      obesity-related behaviors and outcomes. The multiple measures at the individual,
      community, and environment levels are designed to maximize the likelihood of
      detecting change. This approach enhances the likelihood for identifying and
      promoting the best methods to promote health and well-being of the children in
      the underserved US Affiliated Pacific Region. TRIAL REGISTRATION: NIH clinical
      trial # NCT01881373.

PMID- 24107086
TI  - Progress in nutritional and health profile of milk and dairy products: a novel
      drug target.
AB  - There is an increasing focus on diet as a tool to maintain human health and
      prevent disease. Milk and milk products of ruminants are important source of fat
      and saturated fatty acids, which are not considered to be very favourable to
      human health, but are valuable sources of nutrients including bioactive fatty
      acids (FA), vitamins, and minerals, which can promote positive health effects.
      The nutritional characteristics of milk and dairy products are related to their
      composition, which depends on the source species, and varies due to numerous
      factors, among which the animal diet is the most important. An improvement in
      milk FA composition and other micronutrients can be reached through an animal
      feeding strategy. Natural pasture-based farming systems increase
      microconstituents that are beneficial to human health (CLA, PUFAs, n-3 FAs,
      antioxidants, vitamins A and E, and Se) and volatile compounds (flavour, and
      terpenes) in milk and cheese. There are still uncertainties about the health
      benefits of various milk FAs and other compounds; deep and extensive long-term
      clinical studies with humans are needed. The contamination of milk and dairy
      products by heavy metals or dioxins has dramatic negative consequences for human
      and livestock health and necessitates very urgent consideration and intervention.

PMID- 24107087
TI  - Ectopic thyroid gland: description of a case and review of the literature.
AB  - The clinical occurrence of ectopic thyroid gland is an infrequently encountered
      condition, resulting from a developmental abnormality during the migration of the
      thyroid anlage from the floor of the primitive foregut to its final position in
      the neck. It can be found along the way of thyroid descent, in the midline, or
      laterally in the neck or even in the mediastinum or under the diaphragm. This
      condition is often asymptomatic, whereas symptoms could be related to ectopic
      thyroid size, to its relationships with surrounding organs or to diseases
      affecting the ectopic thyroid in the same way they involve orthotopic glands.
      Sometimes, a growing mass can lead to the clinical suspicion of a tumor disease.
      On the other hand, thyroid ectopy must be distinguished from metastasis of
      thyroid cancer. Scintigraphy and ultrasonography are the main diagnostic means
      for evaluating ectopic thyroid tissue, whereas fine needle aspiration could be
      useful in the presence of a nodular ectopic gland or when the coexistence of an
      orthotopic thyroid can arise the suspicion of a metastasis from a thyroid cancer.
      Surgical removal is indicated in symptomatic cases, whereas radioiodine ablation
      is reserved to recurrent disease. In this paper we report an emblematic case of
      ectopic thyroid gland and a review of the literature dealing with this condition.

PMID- 24107088
TI  - Wild mushroom extracts potentiate the action of standard antibiotics against
      multiresistant bacteria.
AB  - AIMS: The main objective of this study was to evaluate the capacity of wild
      mushroom extracts to potentiate the action of standard antibiotics, through
      synergisms that allow a decrease in their therapeutic doses and ultimately
      contribute to the reduction of resistances. METHODS AND RESULTS: Wild mushroom
      extracts were applied to different multiresistant micro-organisms (Escherichia
      coli, extended-spectrum beta-lactamase-producing (ESBL) E. coli and methicillin
      resistant Staphylococcus aureus (MRSA), combined with commercial antibiotics
      (penicillin, ampicillin, amoxicillin/clavulanic acid, cefoxitin, ciprofloxacin,
      cotrimoxazol, levofloxacin). Microdilution method was used to determine minimum
      inhibitory concentrations (MICs). The results obtained showed higher synergistic
      effects against MRSA than against E. coli. Mycena rosea and Fistulina hepatica
      were the best extracts for synergistic effects against MRSA. The efficiency of
      Russula delica extract against E. coli 1 (resistant to ampicillin, ciprofloxacin
      and trimethoprim/sulfasoxazole) and E. coli 2 (resistant to
      amoxicillin/clavulanic acid and ampicillin) was higher than that of Leucopaxillus
      giganteus extract; nevertheless, the latter extract exhibited better synergistic
      effects against ESBL E. coli. CONCLUSIONS: This study shows that, similarly to
      plants, some mushroom extracts can potentiate the action of antibiotics
      extensively used in clinical practice for Gram-positive or Gram-negative
      bacteria, with positive action even against multiresistant bacteria. SIGNIFICANCE
      AND IMPACT OF THE STUDY: Mushroom extracts could decrease therapeutic doses of
      standard antibiotics and reduce micro-organism's resistance to those drugs.

PMID- 24107089
TI  - Total synthesis of phenanthroindolizidine alkaloids through an amidyl radical
      cascade/rearrangement reaction.
AB  - A short and general synthesis of the phenanthroindolizidine alkaloids is
      reported, featuring an unusual amidyl radical 5-exo/5-exo/rearrangement cascade
      of a xanthate precursor. Second, using an amidyl radical 5-exo/6-endo cascade to
      synthesize a phenanthroindolizidine alkaloid exclusively has been developed
      through a small structural modification. 

PMID- 24107090
TI  - Socio-economic determinants of helmet-wearing behaviour in Pune city, India.
AB  - This study was an attempt to investigate the socio-economic determinants of
      helmet wearing in an urban setting of India. A household survey using multistage
      cluster random sampling was conducted among 9014 individuals in Pune city from
      March 2008 to February 2009. Among 2259 individuals who reported driving two
      wheeled vehicles, 1509 (66.8%) reported possession of a helmet, and among those
      who had reported possession of a helmet, only 700 (46.0%) reported regular use of
      helmets. The results of multiple logistic regression analysis showed that
      residence, type of family, gender and socio-economic status were significantly
      associated with possession of helmet, and gender, residence and family type were
      significantly associated with regular helmet use while possessing one. In
      conclusion, this study showed that helmet-wearing behaviour is mostly influenced
      by the neighbourhood environment and norms and family and peer influence on
      behaviour rather than education and economic status. 

PMID- 24107091
TI  - Amsterdam infant stool scale is more useful for assessing children who have not
      been toilet trained than Bristol stool scale.

PMID- 24107092
TI  - The Role of the Relative Dye/Photocatalyst Concentration in TiO2 Assisted
      Photodegradation Process.
AB  - Despite photocatalytic degradation is studied generally focusing the catalyst,
      its interaction with the contaminant molecule plays a fundamental role in the
      efficiency of that process. Then, we proposed a comparative study about the
      photodegradation of two well-known dyes, with different acidity/basicity -
      Methylene Blue (MB) and Rhodamine B (RhB), catalyzed by TiO2 nanoparticles,
      varying both dye and photocatalyst concentrations. The results showed that the
      amphoteric character of MB molecules, even in a range of concentration of 5.0
      10.0 mg L(-1) , did not imply in pH variation in solution. Therefore, it did not
      affect the colloidal behavior of TiO2 nanoparticles, independent of the relative
      dye/catalyst concentration. The acid-base character of RhB influenced the
      resultant pH of the solution, implicating in different colloidal behavior of the
      nanoparticles and consequently, in different degradation conditions according to
      dye concentration. As the isoelectric point of TiO2 is between the pH range of
      the RhB solutions used in this study, from 1.0 to 7.5 mg L(-1) , the resultant pH
      was the key factor for degradation conditions, from a well dispersed to an
      agglomerated suspension.

PMID- 24107094
TI  - Are Health Facility Management Committees in Kenya ready to implement financial
      management tasks: findings from a nationally representative survey.
AB  - BACKGROUND: Community participation in peripheral public health facilities has in
      many countries focused on including community representatives in Health Facility
      Management Committees (HFMCs). In Kenya, HFMC roles are being expanded with the
      phased implementation of the Health Sector Services Fund (HSSF). Under HSSF,
      HFMCs manage facility funds which are dispersed directly from central level into
      facility bank accounts. We assessed how prepared HFMCs were to undertake this new
      role in advance of HSSF roll out, and considered the implications for Kenya and
      other similar settings. METHODS: Data were collected through a nationally
      representative sample of 248 public health centres and dispensaries in 24
      districts in 2010. Data collection included surveys with in-charges (n = 248),
      HFMC members (n = 464) and facility users (n = 698), and record reviews. These
      data were supplemented by semi-structured interviews with district health
      managers in each district. RESULTS: Some findings supported preparedness of HFMCs
      to take on their new roles. Most facilities had bank accounts and HFMCs which met
      regularly. HFMC members and in-charges generally reported positive relationships,
      and HFMC members expressed high levels of motivation and job satisfaction.
      Challenges included users' low awareness of HFMCs, lack of training and clarity
      in roles among HFMCs, and some indications of strained relations with in-charges.
      Such challenges are likely to be common to many similar settings, and are
      therefore important considerations for any health facility based initiatives
      involving HFMCs. CONCLUSION: Most HFMCs have the basic requirements to operate.
      However to manage their own budgets effectively and meet their allocated roles in
      HSSF implementation, greater emphasis is needed on financial management training,
      targeted supportive supervision, and greater community awareness and
      participation. Once new budget management roles are fully established,
      qualitative and quantitative research on how HFMCs are adapting to their expanded
      roles, especially in financial management, would be valuable in informing similar
      financing mechanisms in Kenya and beyond.

PMID- 24107095
TI  - Spontaneous resolution to absolute chiral induction: pseudo-Kagome type
      homochiral Zn(II)/Co(II) coordination polymers with achiral precursors.
AB  - It is observed that conglomerate crystallization of achiral precursors yielding
      racemate metal organic frameworks/coordination polymers (MOFs/CPs) can be driven
      to absolute homochiral crystallization of the desired enantiomorph by utilizing a
      suitable chiral induction agent. In a series of crystallization experiments
      isostructural Zn and Co homochiral CPs (1P, 1M and 2P, 2M) are prepared using the
      achiral precursors. In the presence of enantiopure camphoric acid, the
      crystallization process prefers absolute chiral induction over conglomerate
      formation which is established by single crystal X-ray diffraction and CD
      spectroscopy. 

PMID- 24107093
TI  - An update on the impact of pre-transplant transfusions and allosensitization on
      time to renal transplant and on allograft survival.
AB  - BACKGROUND: Blood transfusions have the potential to improve graft survival,
      induce sensitization, and transmit infections. Current clinical practice is to
      minimize transfusions in renal transplantation candidates, but it is unclear if
      the evidence continues to support pre-transplant transfusion avoidance. Changes
      in the Medicare prospective payment system may increase transfusion rates. Thus
      there is a need to re-evaluate the literature to improve the management options
      for renal transplant candidates. METHODS: A review applying a systematic approach
      and conducted using MEDLINE((r)), Embase((r)), and the Cochrane Library for
      English-language publications (timeframe: 01/1984-03/2011) captured 180 studies
      and data from publically available registries and assessed the impact of
      transfusions on allosensitization and graft survival, and the impact of
      allosensitization on graft survival and wait time. RESULTS: Blood transfusions
      continued to be a major cause of allosensitization, with allosensitization
      associated with increased rejection and graft loss, and longer wait times to
      transplantation. Although older studies showed a beneficial effect of transfusion
      on graft survival, this benefit has largely disappeared in the post-cyclosporine
      era due to improved graft outcomes with current practice. Recent data suggested
      that it may be the donor-specific antibody component of allosensitization that
      carried the risk to graft outcomes. CONCLUSIONS: Results of this review indicated
      that avoiding transfusions whenever possible is a sound management option that
      could prevent detrimental effects in patients awaiting kidney transplantation.

PMID- 24107096
TI  - Echocardiographic assessment of beta-adrenoceptor stimulation-induced heart
      failure with reduced heart rate in mice.
AB  - 1. Chronic injection with the beta-adrenoceptor (beta-AR) agonist isoproterenol
      (ISO) has been commonly used as an animal model of beta-AR-induced cardiac
      remodelling and heart failure. This ISO-treated model usually exhibits
      significantly decreased conscious heart rate (HR). However, the HR in treatment
      groups is usually adjusted to the same levels by anaesthesia to assess cardiac
      geometry and function. In the present study, we report a method of
      echocardiographic assessment that represents the true cardiac geometry and
      function under conditions of ISO withdrawal. 2. Briefly, C57BL/6 mice were
      treated with 5 mg/kg per day ISO for 12 weeks. Cardiac geometry and function were
      assessed by high-resolution echocardiography in vehicle (saline) - and ISO
      treated mice that were either conscious or anaesthetized using different
      concentrations of isoflurane. 3. The cardiac beta-AR response was decreased in
      ISO-treated mice, as evidenced by markedly decreased conscious HR. Vehicle- and
      ISO-treated mice did not differ in terms of cardiac geometry or function when HR
      was adjusted to the same level (400 b.p.m.) in both treatment groups, but cardiac
      geometry and function did differ when a low (1%) rather than high (1.5% or 2%)
      isoflurane concentration was used to adjust HR. Furthermore, 3 day ISO withdrawal
      eliminated the difference in conscious HR between the two groups. In addition,
      the groups differed in cardiac geometry and function regardless of the isoflurane
      concentration used. 4. In conclusion, using isoflurane to decrease the HR of
      treated groups to the same level may mask left ventricular dysfunction in ISO
      treated mice. Withdrawal of ISO eliminated the difference in basal HR between the
      ISO-treated and control groups on echocardiography, allowing a more accurate
      assessment of cardiac pathological and functional changes.

PMID- 24107097
TI  - A novel adamantyl benzylbenzamide derivative, AP736, suppresses melanogenesis
      through the inhibition of cAMP-PKA-CREB-activated microphthalmia-associated
      transcription factor and tyrosinase expression.
AB  - Melanogenesis is essential for the protection of skin against UV, but excessive
      production of melanin causes unaesthetic hyperpigmentation. Much effort is being
      made to develop effective depigmenting agents. Here, we found that a tyrosinase
      inhibitor, AP736 (5-adamantan-1-yl-N-(2,4-dihydroxy-benzyl)-2,4-dimethoxy
      benzamide) potently suppresses tyrosinase expression, and the mechanism
      underlying was elucidated. AP736 attenuated the melanin production induced by
      diverse melanogenic stimuli in murine and human melanocytes. It suppressed the
      expression of key melanogenic enzymes; tyrosinase, tyrosinase-related protein-1
      and tyrosinase-related protein-2. The expression of microphthalmia-associated
      transcription factor (MiTF), a major promoter of melanogenesis was also
      decreased. AP736 inhibited the activation of cAMP response element-binding
      protein (CREB) and phosphokinase A (PKA), and cAMP elevation, reflecting that
      cAMP-PKA-CREB signalling axis was suppressed, resulting in the downregulation of
      MiTF and tyrosinase. Along with the previously reported tyrosinase inhibitory
      activity, the suppression of cAMP-PKA-CREB-mediated MiTF and tyrosinase
      expression by AP736 may be efficient for the treatment for hyperpigmentation. 

PMID- 24107098
TI  - In vitro evaluation of Midwest Caries ID: a novel light-emitting diode for caries
      detection.
AB  - INTRODUCTION: Traditional detection techniques have limits in diagnosing occlusal
      caries. Thus, more accurate methods are needed. This study evaluates the ability
      of the Midwest Caries ID (Midwest) to detect caries. METHODS: Two hundred sixty
      four extracted, nonrestored premolars and molars were cleaned and stored in 0.2%
      sodium azide. Teeth were divided into three groups of 88. One examination site on
      each occlusal surface was chosen. Each site was inspected by a calibrated
      examiner via visual, Midwest, and histologic exams. First, a visual exam was
      performed following the International Caries Detection and Assessment guidelines.
      Next, the same site was inspected using the Midwest device. Finally, the tooth
      was sectioned mesiodistally through the site. The half with greater caries
      progression was visualized under a stereomicroscope (64*). Histologic appearance
      was scored based on the Downer system. Data were analyzed using Kendall tau-b,
      partial correlation coefficients, and the receiver operating characteristics
      curve. RESULTS: Overall, the Midwest scoring assessment correlated with
      histologic assessments (tau = 0.32; p<0.0001), but the visual exam had a stronger
      correlation (tau = 0.53; p<0.0001) with the histologic exam. The sensitivity and
      specificity of the Midwest was also reported at 0.56 and 0.84, compared with 0.92
      and 0.43, respectively, for the visual exam. CONCLUSIONS: Midwest Caries ID is a
      novel caries detection device that has limitations and should not be used as the
      sole means to detect occlusal caries.

PMID- 24107099
TI  - Hepatocytes response to interferon alpha levels recorded after liver resection.
AB  - Extensive damage of liver parenchyma stimulates hepatic cells to transit from
      quiescence to proliferation with eventual restoration of liver mass and function.
      Our recent studies have revealed upregulated expression of interferon (IFN)-alpha
      and its antiviral activity during the early hours after partial hepatectomy. In
      this study, we analyzed the response of primary hepatocytes from intact liver to
      IFN-alpha mimicking its levels (250 U/mL) during the transition period of liver
      restoration. The gene expression profile was analyzed with rat genome array 230
      2.0 (Affymetrix). After 3- and 6-h treatment we identified respectively 28 and
      124 differentially expressed genes responsible for autonomous changes in
      hepatocytes and those involving non-parenchymal cells in a concerted response to
      IFN-alpha. The response has an energy sparing character and affects all levels of
      gene expression. The factors activating T cells and apoptosis are opposed by
      those restricting the signal propagation, inhibiting T cells activation, and
      promoting survival. The partial resemblance between the specific in vitro
      response to IFN-alpha and the processes in regenerating liver is discussed. Our
      study opens the way to a more focused investigation of the liver cell response to
      quasiphysiological dose of IFN-alpha. 

PMID- 24107100
TI  - Tumor-targeting transferrin nanoparticles for systemic polymerized siRNA delivery
      in tumor-bearing mice.
AB  - Transferrin (TF) is widely used as a tumor-targeting ligand for the delivery of
      anticancer drugs because the TF receptor is overexpressed on the surface of
      various fast-growing cancer cells. In this article, we report on TF nanoparticles
      as an siRNA delivery carrier for in vivo tumor-specific gene silencing. To
      produce siRNA carrying TF nanoparticles (NPs), both TF and siRNA were chemically
      modified with sulfhydryl groups that can build up self-cross-linked siRNA-TF NPs.
      Self-polymerized 5'-end thiol-modified siRNA (poly siRNA, psi) and thiolated
      transferrin (tTF) were spontaneously cross-linked to form stable NPs (psi-tTF
      NPs) under optimized conditions, and they could be reversibly degraded to release
      functional monomeric siRNA molecules under reductive conditions. Receptor
      mediated endocytosis of TF induced rapid tumor-cell-specific uptake of the psi
      tTF NPs, and the internalized NPs resulted in a downregulation of the target
      protein in red-fluorescent-protein-expressing melanoma cancer cells (RFP/B16F10)
      with negligible cytotoxicity. After systemic administration, the psi-tTF NPs
      showed marked accumulation at the tumor, leading to successful target-gene
      silencing in vivo. This psi-tTF NP system provided a safe and effective strategy
      for in vivo systemic siRNA delivery for cancer therapy. 

PMID- 24107101
TI  - Comb-like amphiphilic copolymers bearing acetal-functionalized backbones with the
      ability of acid-triggered hydrophobic-to-hydrophilic transition as effective
      nanocarriers for intracellular release of curcumin.
AB  - The pH-responsive micelles have enormous potential as nanosized drug carriers for
      cancer therapy due to their physicochemical changes in response to the tumor
      intracellular acidic microenvironment. Herein, a series of comb-like amphiphilic
      copolymers bearing acetal-functionalized backbone were developed based on
      poly[(2,4,6-trimethoxybenzylidene-1,1,1-tris(hydroxymethyl) ethane methacrylate
      co-poly(ethylene glycol) methyl ether methacrylate] [P(TTMA-co-mPEGMA)] as
      effective nanocarriers for intracellular curcumin (CUR) release. P(TTMA-co
      mPEGMA) copolymers with different hydrophobic-hydrophilic ratios were prepared by
      one-step reversible addition fragmentation chain transfer (RAFT) copolymerization
      of TTMA and mPEGMA. Their molecular structures and chemical compositions were
      confirmed by (1)H NMR, Fourier transform infrared spectroscopy (FT-IR) and gel
      permeation chromatography (GPC). P(TTMA-co-mPEGMA) copolymers could self-assemble
      into nanosized micelles in aqueous solution and displayed low critical micelle
      concentration (CMC). All P(TTMA-co-mPEGMA) micelles displayed excellent drug
      loading capacity, due to the strong pi-pi conjugate action and hydrophobic
      interaction between the PTTMA and CUR. Moreover, the hydrophobic PTTMA chain
      could be selectively hydrolyzed into a hydrophilic backbone in the mildly acidic
      environment, leading to significant swelling and final disassembly of the
      micelles. These morphological changes of P(TTMA-co-mPEGMA) micelles with time at
      pH 5.0 were determined by DLS and TEM. The in vitro CUR release from the micelles
      exhibited a pH-dependent behavior. The release rate of CUR was significantly
      accelerated at mildly acidic pH of 4.0 and 5.0 compared to that at pH 7.4.
      Toxicity test revealed that the P(TTMA-co-mPEGMA) copolymers exhibited low
      cytotoxicity, whereas the CUR-loaded micelles maintained high cytotoxicity for
      HepG-2 and EC-109 cells. The results indicated that the novel P(TTMA-co-mPEGMA)
      micelles with low CMC, small and tunable sizes, high drug loading, pH-responsive
      drug release behavior, and good biocompatibility may have potential as
      hydrophobic drug delivery nanocarriers for cancer therapy with intelligent
      delivery. 

PMID- 24107102
TI  - Direct assessment of phytochemicals inherent in plant tissues using extractive
      electrospray ionization mass spectrometry.
AB  - An ambient pressure ionization mass spectrometric strategy called internal
      extractive electrospray ionization mass spectrometry (iEESI-MS) has been
      developed and applied for direct profiling of labile phytochemicals inherent in
      various native plant tissues, including leaves, roots, and fruits. By passing the
      electrospray solvent through the plant tissue, a variety of phytochemicals, such
      as amino acids, sugars (e.g., glucose, sucrose, polysaccharides, etc.), and
      alkaloids, were continuously extracted from the sample interior, driven toward
      the natural/cut electro-spraying tip, and vaporized into gaseous ions for mass
      spectrometric interrogation. Phytochemical patterns obtained by iEESI-MS permit a
      rapid differentiation between various species of ginkgo plant and strawberry
      maturity stages, as well as characterization of physiological/pathologic
      conditions of chlorophytum comosum. Our experimental results further demonstrate
      that the established iEESI-MS approach is potentially useful for direct
      phytochemomics studies with minimal biodegradation, allowing elucidation of plant
      metabolism with high speed, specificity, and simplicity of analysis. 

PMID- 24107103
TI  - Strain dependence of diet-induced NASH and liver fibrosis in obese mice is linked
      to diabetes and inflammatory phenotype.
AB  - BACKGROUND & AIMS: Obese Alms1 mutant (foz/foz) NOD.B10 mice develop diabetes and
      fibrotic NASH when fed high-fat(HF) diet. To establish whether diabetes or
      obesity is more closely associated with NASH fibrosis, we compared diabetic
      foz/foz C57BL6/J with non-diabetic foz/foz BALB/c mice. We also determined
      hepatic cytokines, growth factors and related profibrotic pathways. METHODS: Male
      and female foz/foz BALB/c and C57BL6/J mice were fed HF or chow for 24 weeks
      before determining metabolic indices, liver injury, cytokines, growth factors,
      pathology/fibrosis and matrix deposition pathways. RESULTS: All foz/foz mice were
      obese. Hepatomegaly, hyperinsulinemia, hyperglycaemia and hypoadiponectinaemia
      occurred only in foz/foz C57BL6/J mice, whereas foz/foz BALB/c formed more
      adipose. Serum ALT, steatosis, ballooning, liver inflammation and NAFLD activity
      score were worse in C57BL6/J mice. In HF-fed mice, fibrosis was severe in foz/foz
      C57BL6/J, appreciable in WT C57BL6/J, but absent in foz/foz BALB/c mice. Hepatic
      mRNA expression of TNF-alpha, IL-12, IL-4, IL-10 was increased (but not IFN
      gamma, IL-1beta, IL-17A), and IL-4:IFN-gamma ratio (indicating Th-2 predominance)
      was higher in HF-fed foz/foz C57BL6/J than BALB/c mice. In livers of HF-fed
      foz/foz C57BL6/J mice, TGF-beta was unaltered but PDGFalpha and CTGF were
      increased in association with enhanced alpha-SMA, CD147and MMP activity.
      CONCLUSIONS: In mice with equivalent genetic/dietary obesity, NASH development is
      linked to strain differences in hyperinsulinaemia and hyperglycaemia inversely
      related to lipid partitioning between adipose and liver. Diabetes-mediated CTGF
      regulation of MMPs as well as cytokines/growth factors (Th-2 cytokine
      predominant, PDGFalpha, not TGF-beta) mobilized in the resultant hepatic
      necroinflammatory change may contribute to strain differences in NASH fibrosis.

PMID- 24107105
TI  - Survey on the occurrence of photo-initiators and amine synergists in cartonboard
      packaging on the German market and their migration into the packaged foodstuffs.
AB  - In  a surveillance study from 2008 to 2011, in total 310 food products,
      predominately packed in cartonboard, were collected from the German market.
      First, the packaging materials were analysed for their content of six photo
      initiators and five amine synergists by high-performance liquid chromatography
      with diode array detection (HPLC-DAD). If high amounts of these substances were
      detected, subsequently the foodstuffs were analysed by means of HPLC-MS or tandem
      MS, respectively. Benzophenone (BP) was detected in 49% of the packaging
      materials and was thus the most often determined compound, followed by 4
      methylbenzophenone (MBP, 8%), 1-hydroxy-cyclohexylphenylketone (HCHPK, 7%) and
      methyl-o-benzoylbenzoate (MOBB, 5%). In total, 99 foodstuffs were analysed and in
      20 cases one or more photo-initiators and/or amine synergists were detected in
      quantities above the legally acceptable limits in food. This resulted in several
      notifications in the European Rapid Alert System for Food and Feed (RASFF); the
      best known is MBP in breakfast cereals. Contamination of the foodstuff by the
      photo-initiators and/or amine synergists also occurred when it was in indirect
      contact with the printed packaging material and no adequate barrier material was
      used to prevent migration. The data also clearly demonstrate that polyethylene
      films are not suitable to inhibit migration. Storage of samples until the best
      before date showed that HCHPK, BP and MBP migrate very easily via the gas phase.
      In contrast, 4-phenylbenzophenone and 4,4'-bis(diethylamino)benzophenone migrated
      only very slowly or, respectively, not in quantifiable amounts into the
      foodstuffs. Differences in transfer rates for HCHPK, BP and MBP from several
      packagings into food and Tenax((r)), respectively, lead to the assumption that
      both the food matrix as well as the extent of cross-linking of the printing ink
      during curing may have an influence on the level of migration. 

PMID- 24107104
TI  - Synthesis and pharmacological evaluation of aminothiazolomorphinans at the mu and
      kappa opioid receptors.
AB  - Previous studies with aminothiazolomorphinans suggested that this class of opioid
      ligands may be useful as a potential pharmacotherapeutic to decrease drug abuse.
      Novel aminothiazole derivatives of cyclorphan were prepared to evaluate a series
      of aminothiazolomorphinans with varying pharmacological properties at the kappa
      opioid receptor (KOR) and MU opioid receptor (MOR). This study was focused on
      exploring the regioisomeric analogs with the aminothiazole on the C-ring of the
      morphinan skeleton. Receptor binding and [(35)S]GTPgammaS binding assays were
      used to characterize the affinity and pharmacological properties of the
      aminothiazolomorphinans. Intracranial self-stimulation (ICSS) was used to compare
      the effects of a representative aminothiazolomorphinan with the morphinan mixed
      KOR/MOR agonist butorphan (MCL-101) on brain-stimulation reward. 

PMID- 24107106
TI  - Processing medical data: a systematic review.
AB  - BACKGROUND: Medical data recording is one of the basic clinical tools. Electronic
      Health Record (EHR) is important for data processing, communication, efficiency
      and effectiveness of patients' information access, confidentiality, ethical
      and/or legal issues. Clinical record promote and support communication among
      service providers and hence upscale quality of healthcare. Qualities of records
      are reflections of the quality of care patients offered. METHODS: Qualitative
      analysis was undertaken for this systematic review. We reviewed 40 materials
      Published from 1999 to 2013. We searched these materials from databases including
      ovidMEDLINE and ovidEMBASE. Two reviewers independently screened materials on
      medical data recording, documentation and information processing and
      communication. Finally, all selected references were summarized, reconciled and
      compiled as one compatible document. RESULT: Patients were dying and/or getting
      much suffering as the result of poor quality medical records. Electronic health
      record minimizes errors, saves unnecessary time, and money wasted on processing
      medical data. CONCLUSION: Many countries have been complaining for
      incompleteness, inappropriateness and illegibility of records. Therefore creating
      awareness on the magnitude of the problem has paramount importance. Hence
      available correct patient information has lots of potential in reducing errors
      and support roles.

PMID- 24107107
TI  - The flexible Ba7UM2S12.5O0.5 (M = V, Fe) compounds: syntheses, structures and
      spectroscopic, resistivity, and electronic properties.
AB  - Two new compounds, Ba7UV2S12.5O0.5 and Ba7UFe2S12.5O0.5, have been synthesized in
      fused-silica tubes by the direct combinations of V or Fe with U, BaS, and S at
      1223 K. The compound Ba7UV2S12.5O0.5 crystallizes at 100 K in the Cs7Cd3Br17
      structure type in space group D4h(18)-I4/mcm of the tetragonal system. The
      compound Ba7UFe2S12.5O0.5 crystallizes at 100 K in space group D4h(5)-P4/mbm of
      the tetragonal system. The structures are very similar with V/S or Fe/S networks
      in which Ba atoms reside as well as channels large enough to accommodate
      additional Ba atoms and infinite linear US5O chains. Each U atom is octahedrally
      coordinated to four equatorial S atoms, one axial S atom, and one axial O atom.
      The Fe/S network contains a S-S single bond, whereas the V/S network does not.
      The result is that the Fe3+ compound charge balances with 7 Ba2+, U4+, 2 Fe3+,
      10.5 S2-, S2(2-), and 0.5 O2-, whereas the V4+ compound charge balances with 7
      Ba2+, U4+, 2 V4+, 12.5 S2-, and 0.5 O2-. Other differences between these two
      compounds have been characterized by Raman spectroscopy and resistivity
      measurements. DFT calculations have provided insight into the nature of their
      bonding. The overall structural motif of Ba7UV2S12.5O0.5 and Ba7UFe2S12.5O0.5
      offers a remarkable flexibility in terms of the oxidation state of the
      incorporated transition metal.

PMID- 24107108
TI  - p38 MAP kinase inhibitors as anti inflammatory agents.
AB  - The p38 Mitogen-Activated Protein (MAP) kinase, a serine/threonine kinase, is one
      of the best characterized kinases in the inflammatory process. Among the four
      identified p38 isoforms (p38alpha, p38beta, p38gamma, and p38delta), the alpha
      form is the most fully studied and plays a central role in the biosynthesis of
      the proinflammatory cytokines i.e. IL-1beta and TNF-alpha at the translational
      and transcriptional levels. Antagonism of these proinflammatory cytokines has
      been recognized as an effective possibility for the development of new drug
      candidates. The characterization of the pharmacological profile displayed by the
      selective p38 inhibitor prototype SB203580, proved its disease-modifying activity
      in the adjuvantinduced arthritis model. This strongly suggests that adequate
      modulation of production of these cytokines can bring significant benefits to the
      therapy of chronic inflammatory diseases. In addition to its important role for
      the secretion of proinflammatory cytokines, p38 is also involved in the
      activation of matrix metalloproteinases and the induction of COX- 2
      transcription, proteins that are involved in the process of tissue destruction
      and inflammation. Because of its multiple functions in modulating the
      inflammatory response, it is expected that p38 inhibiting drugs will treat the
      underlying cause of chronic inflammatory diseases and stop their progression. The
      archetypal small molecule p38 inhibitors are the pyridinylimidazoles and these
      structures formed the basis for much of the early research. More recently a
      number of nonimidazole based p38 inhibitors such as the ureas, pyrazoles,
      pyrazoloheteroaryls, pyridazines, indoles, amides, pyridines, triazolopyridines,
      etc containing a variety of functionality have been reported to inhibit cytokine
      activity. This article provides a critical account of these different
      heterocycles reported for p38 MAPK inhibition and covers the recent research in
      the development of anti inflammatory agents. 

PMID- 24107109
TI  - Diameters of left gastric vein and its originating vein on magnetic resonance
      imaging in liver cirrhosis patients with hepatitis B: Association with endoscopic
      grades of esophageal varices.
AB  - AIM: To determine whether diameters of the left gastric vein (LGV) and its
      originating vein are associated with endoscopic grades of esophageal varices.
      METHODS: Ninety-eight liver cirrhotic patients with hepatitis B undergoing
      magnetic resonance (MR) portography, and upper gastrointestinal endoscopy for
      grading esophageal varices were enrolled. Diameters of the LGV and its
      originating vein - the splenic vein (SV) or portal vein (PV) - were measured on
      MR imaging. Statistical analyses were performed to identify the association of
      the diameters with the endoscopic grades. RESULTS: Univariate analysis showed
      that the SV was predominantly the originating vein of the LGV, and diameters of
      the LGV and SV were associated with grades of esophageal varices. Diameters of
      the LGV (P = 0.023, odds ratio [OR] = 1.583) and SV (P = 0.012, OR = 2.126) were
      independent risk factors of presence of the varices. Cut-off LGV diameters of 5.1
      mm, 5.9 mm, 6.6 mm, 7.1 mm, 7.8 mm and 5.8 mm; or cut-off SV diameters of 7.3 mm,
      7.9 mm, 8.4 mm, 9.5 mm, 10.7 mm and 8.3 mm, could discriminate grades 0 from 1, 0
      from 2, 0 from 3, 1 from 3, 2 from 3, and 0-1 from 2-3, respectively. CONCLUSION:
      Diameters of the LGV and SV are associated with endoscopic grades of esophageal
      varices.

PMID- 24107110
TI  - Aqueous solution-processed GeO2: an anode interfacial layer for high performance
      and air-stable organic solar cells.
AB  - A simple and cheap method for depositing solution-processed GeO2 (sGeO2) film is
      proposed utilizing the weak solubility of GeO2 in water. X-ray photoelectron
      spectroscopy analysis reveals that a pure GeO2 thin film can be formed by casting
      its aqueous solution. This method can avoid the difficulty of vacuum evaporation
      by its high melting point. The sGeO2 film has been used successfully as an anode
      interfacial layer in poly(3-hexylthiophene) (P3HT) and indene-C60 bisadduct
      (IC60BA)-based bulk heterojunction organic solar cells with improved power
      conversion efficiency and device stability compared with that using conventional
      poly (3,4-ethylenedioxythiophene):poly (styrenesulfonate) (PEDOT:PSS); the
      improvement of the power conversion efficiency and the device stability are
      estimated to be 9% and 50%, respectively. The calculations of optical intensity
      in a whole cell demonstrate that a thin layer of sGeO2 could function as an
      optical spacer in the based bulk heterojunction (BHJ) organic solar cells (OSCs)
      for enhancing the light harvesting in the active layer. Interfacial evaluation by
      impedance spectroscopy shows that the sGeO2-based cell exists less charge carrier
      recombination and lower contact resistance. More importantly, the sGeO2 film
      processing is very simple and environmentally friendly, which has potential
      applications in green and low-cost organic electronics in the future. 

PMID- 24107111
TI  - Respiratory symptoms and lung function 8-10 months after community exposure to
      chlorine gas: a public health intervention and cross-sectional analysis.
AB  - BACKGROUND: We implemented a community based interventional health screening for
      individuals located within one mile of a 54 metric tons release of liquid
      chlorine following a 16 tanker car train derailment on 6 January, 2005 in
      Graniteville, South Carolina, USA. Public health intervention occurred 8-10
      months after the event, and provided pulmonary function and mental health
      assessment by primary care providers. Its purpose was to evaluate those exposed
      to chlorine for evidence of ongoing impairment for medical referral and
      treatment. We report comparative analysis between self-report of respiratory
      symptoms via questionnaire and quantitative spirometry results. METHODS: Health
      assessments were obtained through respiratory symptom and exposure
      questionnaires, simple spirometry, and physical exam. Simple spirometry was used
      as the standard to identify continued breathing problems. Sensitivity,
      specificity, positive and negative predictive values were applied to evaluate the
      validity of the respiratory questionnaire. We also identified the direction of
      discrepancy between self-reported respiratory symptoms and spirometry measures.
      Generalized estimation equations determined prevalence ratios for abnormal
      spirometry based on the presence of participant persistent respiratory symptoms.
      Covariate adjustment was made for participant age, sex, race, smoking and
      educational status. RESULTS: Two hundred fifty-nine people participated in the
      Graniteville health screening; 53 children (mean age = 11 years, range: <1-16),
      and 206 adults (mean age = 50 years, range: 18-89). Of these, 220 (85%) performed
      spirometry maneuvers of acceptable quality. Almost 67% (n = 147) displayed
      abnormal spirometry, while 50% (n = 110) reported persistent new-onset
      respiratory symptoms. Moreover, abnormal spirometry was seen in 65 participants
      (29%) who did not report any discernible breathing problems. This represented a
      net 16.8% underreporting of symptoms. Sensitivity and specificity of
      questionnaire self-report of symptoms were low at 55.8% and 61.6%, respectively.
      Persistent cough (41%) and shortness of breath (39%) were the most frequently
      reported respiratory symptoms. CONCLUSION: Eight to ten months after acute
      chlorine exposure, the Graniteville health screening participants under-reported
      respiratory symptoms when compared to abnormal spirometry results. Sensitivity
      and specificity were low, and we determined that relying upon the self-report
      questionnaire was not adequate to objectively assess the lung health of our
      population following irritant gas exposure.

PMID- 24107113
TI  - Emotional dysfunction in avoidant compared to borderline personality disorder: a
      study of affect consciousness.
AB  - Knowledge of emotional dysfunction in patients with avoidant personality disorder
      (APD) is much needed. The present study examined affect consciousness (AC) in
      patients with APD compared to borderline personality disorder (BPD). AC, defined
      as capacity to perceive, reflect on, tolerate, and express emotional experiences,
      is assumed to be central to structure-building in personality. The study tested
      the hypotheses that patients with APD have lower general AC and lower AC for
      pleasant affects compared to BPD. Fifty-nine patients, 26 with APD and 33 with
      BPD were rated on several aspects of AC using the specialized AC interview. The
      structured interview SCID-II was applied for diagnostic evaluations. The APD
      group had significantly lower levels of global AC and conceptual expressivity
      compared to the BPD group. Among 11 specific affects the APD group had
      significantly lower AC for interest and contempt. Emotional dysfunction is an
      important feature of APD and the findings indicate that psychotherapies for APD
      patients should focus on emotional experiences, aiming to improve emotional
      awareness, tolerance, and expressivity. The notion of a general avoidance of
      positive emotions in APD needs further exploration, including a possible
      dysfunction in the evolutionary based neuro-affective Seeking system. 

PMID- 24107112
TI  - Phase I study of injectable, depot naltrexone for the relapse prevention
      treatment of opioid dependence.
AB  - BACKGROUND AND OBJECTIVES: We tested long-acting injectable depot naltrexone for
      its tolerability, pharmacokinetics, and safety in Phase I. METHODS: The Phase I
      trial enrolled 36 healthy participants in two panels (A, B). In Panel A, 24
      subjects were randomly assigned to the high-dosage group (400 mg naltrexone, n=6;
      placebo, n=6) or low-dosage group (200 mg naltrexone, n=6; placebo, n=6). In
      Panel B, 12 subjects were randomized to take six doses of monthly injectable
      naltrexone (400 mg) or placebo. RESULTS: After a single injection of naltrexone
      200 and 400 mg, means (SD) of naltrexone plasma concentrations were .57 (.28)
      ng/ml and 1.5 (.8) ng/ml 30 days post-injection. There was no effect of
      accumulation after multiple dosing. Eleven of 30 subjects (36.67%) who were
      administered injectable depot naltrexone reported a total of 12 adverse events
      (AEs). Seven of these 11 AEs were coded as possibly related with study
      medication. All treatment-related AEs were mild in severity. No serious treatment
      related AEs occurred. DISCUSSION AND CONCLUSIONS: This long-acting formulation of
      injectable depot naltrexone is well tolerated, results in constant plasma
      concentration of naltrexone for at least 1 month. SCIENTIFIC SIGNIFICANCE: The
      tolerability and safety of long-acting injectable depot naltrexone are good.

PMID- 24107114
TI  - Tuning reactivity of glycosyl imidinium intermediate for 2-azido-2-deoxyglycosyl
      donors in alpha-glycosidic bond formation.
AB  - The chemical properties of nucleophile additives were investigated in a modulated
      glycosylation context. N-Formylmorpholine (NFM) was found to be an effective
      modulator for glycosylation with less reactive 2-azido-2-deoxythioglucosyl and
      thiogalactosyl donors. 

PMID- 24107115
TI  - Photochemical reduction of carbon dioxide to methanol and formate in a
      homogeneous system with pyridinium catalysts.
AB  - Photochemical catalytic CO2 reduction to formate and methanol has been
      demonstrated in an aqueous homogeneous system at pH 5.0 comprising ruthenium(II)
      trisphenanthroline as the chromophore, pyridine as the CO2 reduction catalyst,
      KCl, and ascorbic acid as a sacrificial reductant, using visible light
      irradiation at 470 +/- 20 nm. Isotopic labeling with (13)CO2 yields the six
      electron-reduced product (13)CH3OH. After 1 h photolysis, the two-electron
      reduced product formate and the six-electron-reduced product methanol are
      produced with quantum yields of 0.025 and 1.1 * 10(-4), respectively. This
      represents 76 and 0.15 turnovers per Ru for formate and methanol, respectively,
      and 152 and 0.9 turnovers per Ru on an electron basis for formate and methanol,
      respectively. The system is inactive after 6 h irradiation, which appears largely
      to be due to chromophore degradation. A partial optimization of the methanol
      yield showed that high pyridine to Ru ratios are needed (100:1) and that the
      optimum pH is near 5.0. The presence of potassium salts enhances the yield in
      formate and methanol by 8- and 2-fold, respectively, compared to electrolyte-free
      solutions; however, other alkali and alkali earth cations have little effect. The
      addition of small amounts of solid metal catalysts immobilized on carbon had
      either no effect (M = Pt or Pd) or deleterious effects (M = Ni or Au) on methanol
      production. Addition of colloidal Pt resulted in no methanol production at all.
      This is in notable contrast with the pyridine-based electrocatalysis of CO2 to
      methanol in which metallic or conductive surfaces such as Pt, Pd, or p-type GaP
      are necessary for methanol formation.

PMID- 24107116
TI  - Home and health in people ageing with Parkinson's disease: study protocol for a
      prospective longitudinal cohort survey study.
AB  - BACKGROUND: With an increased life expectancy for the general population as well
      as for those ageing with chronic diseases, there are major challenges to the
      affected individuals and their families, but also to health care and societal
      planning. Most important, an increasing proportion of older people remain living
      in their ordinary homes despite health decline and disability. However, little is
      known about the home and health situation of people ageing with Parkinson's
      disease (PD), and older people are often excluded from PD-research.
      METHODS/DESIGN: The overall aim of the present project is to generate knowledge
      on home and health dynamics in people with PD, with an explicit attention to PD
      specific symptomatology. We will concentrate on aspects of home and health
      captured by state-of-the-art methodology from gerontology as well as PD-research,
      health science and rehabilitation. This study protocol describes a longitudinal
      cohort survey study that includes a baseline data collection and a 3-year follow
      up. Both data collection waves include self-administered questionnaires,
      structured interviews, clinical assessments and observations during home visits
      effectuated by research staff with project-specific training. In order to arrive
      at a follow-up sample of N=160, 250 participants identified by PD specialist
      nurses are being recruited from three hospitals in southern Sweden. With no lower
      or upper age limit, only those diagnosed with PD since at least one year were
      included. The exclusion criteria were: difficulties in understanding or speaking
      Swedish and/or cognitive difficulties/other reasons making the individual unable
      to give informed consent or to take part in the majority of the data collection.
      The data collection targets environmental factors such as assistive devices,
      social support, physical environmental barriers, accessibility problems and
      perceived aspects of home. A broad variety of instruments tap PD-specific
      problems (e.g. freezing of gait, fear of falling) and health-related issues such
      as general self-efficacy, body functions, activities and participation.
      DISCUSSION: This project will produce knowledge to the benefit of the development
      of health care and societal planning that targets people ageing with PD,
      ultimately promoting activity and participation and an increase of the number of
      healthy life years for this sub-group of the population.

PMID- 24107120
TI  - 100 years of the Maillard reaction: why our food turns brown.

PMID- 24107121
TI  - Identification of important and potentially avoidable risk factors in a
      prospective audit study of neonatal deaths in a paediatric hospital in Vietnam.
AB  - AIM: Neonatal deaths (<=28 days) account for more than half of child mortality in
      Vietnam. Presumably most die in hospital, but data are scarce. This study aimed
      to identify risk factors of death among hospitalised neonates. METHODS: We
      prospectively studied all neonatal deaths and expected deaths (discharged alive
      after withdrawal of life-sustaining treatment) in a Vietnamese tertiary
      paediatric hospital during a 12-month period in 2009-2010. The medical files were
      audited classifying admission prognosis, discharge outcome, cause of
      death/expected death according to two classifications, and important and
      potentially avoidable risk factors during the hospital stay. RESULTS: Among 5763
      neonates admitted, 235 deaths and 67 expected deaths were included. According to
      both classifications, major causes were congenital malformations, prematurity and
      severe infections. Six risk factors were identified in 85% (60/71) of the
      neonates with a relatively good prognosis: recognition or response to danger
      signs, internal transfers, nosocomial infections, sepsis management, access to
      usual equipment/staff, and family perception. CONCLUSION: Among 302 neonatal
      deaths/expected deaths, the major causes were congenital malformations,
      prematurity and severe infections. Six important and potentially avoidable risk
      factors could be addressed in the subgroup with relatively good admission
      prognosis, without implementing new technology or major organisational changes.

PMID- 24107122
TI  - Cat-scratch disease.
AB  - PURPOSE: To discuss the systemic and ocular manifestations, diagnosis and
      treatment of Bartonella infection. METHOD: Review of the literature. RESULTS:
      Bartonella are facultative intracellular Gram-negative rods that infect the
      erythrocytes or endothelial cells and are related to cat scratch disease (CSD).
      Bartonella henselae infection has localized or systemic features; the ocular
      diseases related to Bartonella affect 5--10% of patients with CSD. The diagnosis
      is based on clinical findings and laboratory tests. The indication of antibiotic
      therapy depends on the manifestation of the Bartonella infection, the host
      immunity and the patient's age. CONCLUSION: Physicians should look for Bartonella
      henselae in cases of follicular conjuntivitis and regional limphadenopathy,
      neuroretinitis or retinal infiltrates; currently, serological tests can confirm
      the clinical suspicion of this infection.

PMID- 24107123
TI  - Drug repositioning as a route to anti-malarial drug discovery: preliminary
      investigation of the in vitro anti-malarial efficacy of emetine dihydrochloride
      hydrate.
AB  - BACKGROUND: Drug repurposing or repositioning refers to the usage of existing
      drugs in diseases other than those it was originally used for. For diseases like
      malaria, where there is an urgent need for active drug candidates, the strategy
      offers a route to significantly shorten the traditional drug development
      pipelines. Preliminary high-throughput screens on patent expired drug libraries
      have recently been carried out for Plasmodium falciparum. This study reports the
      systematic and objective further interrogation of selected compounds reported in
      these studies, to enable their repositioning as novel stand-alone anti-malarials
      or as combinatorial partners. METHODS: SYBR Green flow cytometry and micro-titre
      plate assays optimized in the laboratory were used to monitor drug susceptibility
      of in vitro cultures of P. falciparum K1 parasite strains. Previously described
      fixed-ratio methods were adopted to investigate drug interactions. RESULTS:
      Emetine dihydrochloride hydrate, an anti-protozoal drug previously used for
      intestinal and tissue amoebiasis was shown to have potent inhibitory properties
      (IC50 doses of ~ 47 nM) in the multidrug resistant K1 strain of P. falciparum.
      The sum 50% fractional inhibitory concentration (?FIC50, 90) of the interaction
      of emetine dihydrochloride hydrate and dihydroartemisinin against the K1 strains
      of P. falciparum ranged from 0.88-1.48. CONCLUSION: The results warrant further
      investigation of emetine dihydrochloride hydrate as a potential stand-alone anti
      malarial option. The interaction between the drug and the current front line
      dihydroartemisinin ranged from additive to mildly antagonistic in the fixed drug
      ratios tested.

PMID- 24107124
TI  - The effects of glucose and lipids in steatotic and non-steatotic livers in
      conditions of partial hepatectomy under ischaemia-reperfusion.
AB  - BACKGROUND: Steatosis is a risk factor in partial hepatectomy (PH) under
      ischaemia-reperfusion (I/R), which is commonly applied in clinical practice to
      reduce bleeding. Nutritional support strategies, as well as the role of
      peripheral adipose tissue as energy source for liver regeneration, remain poorly
      investigated. AIMS: To investigate whether the administration of either glucose
      or a lipid emulsion could protect steatotic and non-steatotic livers against
      damage and regenerative failure in an experimental model of PH under I/R. The
      relevance of peripheral adipose tissue in liver regeneration following surgery is
      studied. METHODS: Steatotic and non-steatotic rat livers were subjected to
      surgery and the effects of either glucose or lipid treatment on damage and
      regeneration, and part of the underlying mechanisms, were investigated. RESULTS:
      In non-steatotic livers, treatment with lipids or glucose provided the same
      protection against damage, regeneration failure and ATP drop. Adipose tissue was
      not required to regenerate non-steatotic livers. In the presence of hepatic
      steatosis, lipid treatment, but not glucose, protected against damage and
      regenerative failure by induction of cell cycle, maintenance of ATP levels and
      elevation of sphingosine-1-phosphate/ceramide ratio and phospholipid levels.
      Peripheral adipose tissue was required for regenerating the steatotic liver but
      it was not used as an energy source. CONCLUSION: Lipid treatment in non-steatotic
      livers provides the same protection as that afforded by glucose in conditions of
      PH under I/R, whereas the treatment with lipids is preferable to reduce the
      injurious effects of liver surgery in the presence of steatosis.

PMID- 24107125
TI  - Virtual microscopy is a valid alternative for the diagnostic assessment of
      laryngeal premalignancies.

PMID- 24107126
TI  - Immunogenicity of anti-TNFalpha therapy in psoriasis: a clinical issue?
AB  - INTRODUCTION: Immunogenicity of antitumor necrosis factor-alpha (TNFalpha) agents
      has been proven to play a significant role in the variability of clinical
      responses among patients with chronic inflammatory diseases. However, its
      clinical impact on the outcome of patients with psoriasis and psoriatic arthritis
      receiving anti-TNFalpha treatment is not yet fully clear. Despite the high rates
      of efficacy of anti-TNFalpha agents in psoriasis, a substantial proportion of
      patients remain who experience a primary or secondary failure or significant side
      effects, which are potentially ascribable to immunogenicity. AREAS COVERED:
      Topics include immunologic response elicited by anti-TNFalpha agents, the impact
      of immunogenicity on treatment response to anti-TNFalpha and the role played by
      immunogenicity in the lack of efficacy of anti-TNFalpha agents (infliximab,
      adalimumab and etanercept) in psoriasis. EXPERT OPINION: Based on data available
      in the literature and the clinical experience of the authors, this article
      suggests the optimal approach to drug monitoring and antidrug antibody assay and
      the most effective use of biologic immunotherapies in this setting.
      Immunogenicity should be taken into account in the adoption of therapeutic
      choices in psoriatic patients, such as anti-TNFalpha agent intensification, or
      switching to another anti-TNFalpha agent or a drug with a different mechanism of
      action.

PMID- 24107127
TI  - Birth of the localized surface plasmon resonance in monolayer-protected gold
      nanoclusters.
AB  - Gold nanoclusters protected by a thiolate monolayer (MPC) are widely studied for
      their potential applications in site-specific bioconjugate labeling, sensing,
      drug delivery, and molecular electronics. Several MPCs with 1-2 nm metal cores
      are currently known to have a well-defined molecular structure, and they serve as
      an important link between molecularly dispersed gold and colloidal gold to
      understand the size-dependent electronic and optical properties. Here, we show by
      using an ab initio method together with atomistic models for experimentally
      observed thiolate-stabilized gold clusters how collective electronic excitations
      change when the gold core of the MPC grows from 1.5 to 2.0 nm. A strong localized
      surface plasmon resonance (LSPR) develops at 540 nm (2.3 eV) in a cluster with a
      2.0 nm metal core. The protecting molecular layer enhances the LSPR, while in a
      smaller cluster with 1.5 nm gold core, the plasmon-like resonance at 540 nm is
      confined in the metal core by the molecular layer. Our results demonstrate a
      threshold size for the emergence of LSPR in these systems and help to develop
      understanding of the effect of the molecular overlayer on plasmonic properties of
      MPCs enabling engineering of their properties for plasmonic applications. 

PMID- 24107128
TI  - Effect of mode of delivery on macronutrient content of breast milk.
AB  - OBJECTIVE: To determine the effect of delivery type on macronutrient content of
      colostral milk. MATERIALS AND METHODS: The study was conducted at Zekai Tahir
      Burak Maternity Teaching Hospital. Colostral milk samples from term lactating
      mothers who gave birth by vaginal or cesarean delivery (CD) were obtained on the
      2nd postpartum day. Milk protein, fat, carbohydrate (CHO) and energy levels were
      measured by using a mid-infrared human milk analyzer. RESULTS: A total of 204
      term lactating mothers were recruited to the study; 111 mothers gave birth by
      vaginal route and 93 mothers by CD. Protein levels were statistically lower in
      colostral milk of mothers after CD compared to mothers who delivered vaginally
      (median 2.4 (range 0.3-6.4) g/dl versus 3 (0.5-6.3) g/dl, respectively; p =
      0.036). Colostral fat, CHO and energy levels were similar between groups. In
      linear regression analysis, CD and maternal age were independently associated
      with lower protein content in colostrum. CONCLUSION: Vaginal delivery is
      associated with higher colostrum protein content. Hormonal activity induced by
      labor pain and uterine contractions might account for the alterations in the
      protein composition of human milk to facilitate optimal development of important
      physiologic functions in newborns.

PMID- 24107129
TI  - A robust methodology to subclassify pseudokinases based on their nucleotide
      binding properties.
AB  - Protein kinase-like domains that lack conserved residues known to catalyse
      phosphoryl transfer, termed pseudokinases, have emerged as important signalling
      domains across all kingdoms of life. Although predicted to function principally
      as catalysis-independent protein-interaction modules, several pseudokinase
      domains have been attributed unexpected catalytic functions, often amid
      controversy. We established a thermal-shift assay as a benchmark technique to
      define the nucleotide-binding properties of kinase-like domains. Unlike in vitro
      kinase assays, this assay is insensitive to the presence of minor quantities of
      contaminating kinases that may otherwise lead to incorrect attribution of
      catalytic functions to pseudokinases. We demonstrated the utility of this method
      by classifying 31 diverse pseudokinase domains into four groups: devoid of
      detectable nucleotide or cation binding; cation-independent nucleotide binding;
      cation binding; and nucleotide binding enhanced by cations. Whereas nine
      pseudokinases bound ATP in a divalent cation-dependent manner, over half of those
      examined did not detectably bind nucleotides, illustrating that pseudokinase
      domains predominantly function as non-catalytic protein-interaction modules
      within signalling networks and that only a small subset is potentially
      catalytically active. We propose that henceforth the thermal-shift assay be
      adopted as the standard technique for establishing the nucleotide-binding and
      catalytic potential of kinase-like domains.

PMID- 24107131
TI  - Occurrence of perfluoroalkyl substances (PFASs) in various food items of animal
      origin collected in four European countries.
AB  - This study summarises the results of the levels of 21 perfluoroalkyl substances
      (PFASs) in 50 selected pooled samples representing 15 food commodities with the
      special focus on those of animal origin, as meat, seafood, fish, milk, dairy
      products and hen eggs, which are commonly consumed in various European markets,
      e.g. Czech, Italian, Belgian and Norwegian. A new, rapid sample preparation
      approach based on the QuEChERS extraction procedure was applied. Ultra
      performance liquid chromatography (UHPLC) coupled to tandem mass spectrometry
      (MS/MS) employing electrospray ionisation (ESI) in negative mode was used for the
      quantification of target analytes. Method quantification limits (MQLs) were in
      the range of 1-10 ng kg(-1) (ng l(-1)) for fish, meat, hen eggs, cheese and milk,
      and in the range of 2.5-125 ng kg(-1) for butter. Only 16 of the group of 21
      PFASs were found in at least one analysed sample. From 16 PFASs, perfluorooctane
      sulfonate (PFOS) was the most frequently detected analyte present in
      approximately 50% of samples (in the range of 0.98-2600 ng kg(-1)). PFCAs with C8
      C14 carbon chain were presented in approximately 20% of samples. The
      concentration ranges of individual compounds in the respective groups of PFASs
      were: 2.33-76.3 ng kg(-1) for PFSAs (without PFOS), 4.99-961 ng kg(-1) for PFCAs,
      10.6-95.4 ng kg(-1) for PFPAs, and 1.61-519 ng kg(-1) for FOSA. The contamination
      level in the analysed food commodities decreased in the following order: seafood
      > pig/bovine liver >> freshwater/marine fish > hen egg > meat >> butter. When
      comparing the total contamination and profiles of PFASs in food commodities that
      originated from various sampling countries, differences were identified, and the
      contents decreased as follows: Belgium >> Norway, Italy > Czech Republic. 

PMID- 24107130
TI  - Oxidation of polychlorinated biphenyls by liver tissue slices from phenobarbital
      pretreated mice is congener-specific and atropselective.
AB  - Mouse models are powerful tools to study the developmental neurotoxicity of
      polychlorinated biphenyls (PCBs); however, studies of the oxidation of chiral PCB
      congeners to potentially neurotoxic hydroxylated metabolites (OH-PCBs) in mice
      have not been reported. Here, we investigate the atropselective oxidation of
      chiral PCB 91 (2,2',3,4',6-pentachlorobiphenyl), PCB 95 (2,2',3,5',6
      pentachlorobiphenyl), PCB 132 (2,2',3,3',4,6'-hexachlorobiphenyl), PCB 136
      (2,2',3,3',6,6'-hexachlorobiphenyl), and PCB 149 (2,2',3,4',5',6
      hexachlorobiphenyl) to OH-PCBs in liver tissue slices prepared from female mice.
      The metabolite profile of PCB 136 typically followed the rank order 5-OH-PCB > 4
      OH-PCB > 4,5-OH-PCB, and metabolite levels increased with PCB concentration and
      incubation time. A similar OH-PCB profile was observed with the other PCB
      congeners, with 5-OH-PCB/4-OH-PCB ratios ranging from 2 to 12. More 5-OH-PCB 136
      was formed in liver tissue slices obtained from animals pretreated with
      phenobarbital (P450 2B inducer) or, to a lesser extent, dexamethasone (P450 2B
      and 3A enzyme inducer) compared to tissue slices prepared from vehicle-pretreated
      animals. The apparent rate of 5-OH-PCBs formation followed the approximate rank
      order PCB 149 > PCB 91 > PCB 132 ~ PCB 136 > PCB 95. Atropselective gas
      chromatography revealed a congener-specific atropisomeric enrichment of major OH
      PCB metabolites. Comparison of our results with published OH-PCB patterns and
      chiral signatures (i.e., the direction and extent of the atropisomeric
      enrichment) from rat liver microsomal revealed drastic differences between both
      species, especially following the induction of P450 2B enzymes. These species
      differences in the metabolism of chiral PCBs should be considered in
      developmental neurotoxicity studies of PCBs. 

PMID- 24107132
TI  - Efficient panchromatic organic sensitizers with dihydrothiazole derivative as pi
      bridge for dye-sensitized solar cells.
AB  - Novel organic dyes CC201 and CC202 with dihydrothiazole derivative as pi-bridge
      have been synthesizedand applied in the DSSCs. With the synergy electron
      withdrawing of dihydrothiazole and cyanoacrylic acid, these two novel dyes CC201
      and CC202 show excellent response in the region of 500-800 nm. An efficiency as
      high as 6.1% was obtained for the device fabricated by sensitizer CC202 together
      with cobalt electrolyte under standard light illumination (AM 1.5G, 100 mW cm(
      2)). These two novel D-pi-A panchromatic organic dyes gave relatively high
      efficiencies except common reported squaraine dyes. 

PMID- 24107133
TI  - Delayed response of interfacial tension in propagating chemical waves of the
      Belousov-Zhabotinsky reaction without stirring.
AB  - Time-resolved measurements of the interfacial tension of propagating chemical
      waves of the Belousov-Zhabotinsky reaction based on the iron complex catalysts
      were carried out without stirring by monitoring the frequency of capillary waves
      with the quasi-elastic laser scattering method. A delayed response of the
      interfacial tension with respect to absorption was found with the delay being
      ligand-dependent when the reaction was conducted at a liquid/liquid interface.
      This behavior is attributed to differences in adsorption activity of the
      hydrophobic metal catalyst. The delay time and the increase in interfacial
      tension were also reproduced by a model considering the rate constants of
      equilibrium adsorption. 

PMID- 24107134
TI  - The Study of the Prevention of Anal Cancer (SPANC): design and methods of a three
      year prospective cohort study.
AB  - BACKGROUND: The incidence of human papillomavirus (HPV)-associated anal cancer is
      increasing in men who have sex with men (MSM). Screening for the presumed cancer
      precursor, high-grade anal squamous intraepithelial lesions (HSIL) in a manner
      analogous to cervical cancer screening has been proposed. Uncertainty remains
      regarding anal HPV natural history and the role of anal cytology and high
      resolution anoscopy (HRA) as screening tests. Well-designed cohort studies are
      required to address these issues. METHODS/DESIGN: The SPANC study is a
      prospective study of the epidemiology of low-risk and high-risk anal HPV
      infection and related cytological and histological abnormalities in HIV-negative
      and HIV-positive homosexual men aged 35 years and over. The study aims to recruit
      600 men from community-based settings in Sydney, Australia. There are six study
      visits over three years. At the first five visits men undergo a digital ano
      rectal examination (DARE), an anal "Papanicolaou" (Pap) test for HPV detection,
      genotyping and anal cytology, followed by HRA and directed biopsy of any visible
      abnormalities. The men also complete a behavioural questionnaire before each
      visit. Questions include a detailed history of sexual behaviour, of anal
      symptoms, possible anal cancer risk factors and validated quality of life and
      psychosocial questions. Questionnaires are also completed 2 weeks and 3 months
      following the provision of test results and include questions on participant
      experience during the procedure and post-procedure symptoms, including pain and
      bleeding in addition to quality of life/ psychosocial outcomes. DISCUSSION:
      Recruitment for the study began in September 2010 and will conclude in mid-2015,
      with follow up continuing to 2018. Thus far, over 350 men have been recruited
      from a variety of community-based settings and are broadly representative of the
      target screening population. The SPANC study is one of only a small number of
      cohort studies globally to perform HPV, cytology and HRA screening on all
      participants over multiple time points. The study results will contribute to
      understanding of the natural history of anal HPV and inform the possible
      development of guidelines for implementing anal cancer screening programs in this
      population.

PMID- 24107135
TI  - Idiopathic intracranial hypertension: a possible complication in the natural
      history of advanced prostate cancer.
AB  - Idiopathic intracranial hypertension is a variety of intracranial hypertension
      that is extremely rare in men. Obesity and hypogonadism are the most important
      predictive factors. Etiological hypotheses include increased central venous
      pressure, and various hormonal and metabolic changes commonly found in obese
      patients. We described the case of an obese man with prostate cancer who showed a
      consistent bodyweight increase during treatment with taxanes and prednisone. He
      was hospitalized because of a severe loss of vision as a consequence of
      idiopathic intracranial hypertension. A complete symptom remission was obtained
      after 3 weeks of anti-edema therapies (steroids, acetazolamide). Castration
      resistant prostate cancer is a risk factor for idiopathic intracranial
      hypertension. Long-term androgen deprivation therapy, bodyweight increase, and
      fluid retention during chronic steroid administration and taxane chemotherapy
      might favor the disease onset. This severe complication has a good outcome, and
      should be suspected in the presence of symptoms and signs of intracranial
      hypertension. 

PMID- 24107136
TI  - Extracurricular interest as a resilience building block for children affected by
      parental HIV/AIDS.
AB  - Parental illness and death due to human immunodeficiency virus/acquired
      immunodeficiency syndrome (HIV/AIDS) impose challenges to children's
      psychological adjustment. Positive psychology emphasizes individual's resilience
      in the face of adversity, trauma, and tragedy. Limited data are available
      regarding the factors that can cultivate resilience of children affected by
      HIV/AIDS. This study aims to examine the role of extracurricular interest in
      strengthening resilience among children affected by HIV/AIDS. Participants
      included 755 children orphaned by parental HIV/AIDS, 466 vulnerable children
      living with HIV-positive parent(s), and 404 comparison children from HIV-free
      families in the same community in rural China. The measures include
      extracurricular interest (i.e., reading, sports, music, painting, science, and
      playing chess) and indicators of psychological adjustment (i.e., depression,
      loneliness, and self-esteem). Having extracurricular interest was positively
      associated with self-esteem and negatively associated with depression and
      loneliness. Having extracurricular interest attenuated the negative effect of
      parental HIV/AIDS on children's self-esteem and loneliness, after controlling for
      children's age, gender, and family socioeconomic status. The findings underscore
      the importance of nurturing extracurricular interest and make available of such
      activities to promote resilience for children affected by HIV/AIDS in resource
      limited settings.

PMID- 24107137
TI  - Stearylated antimicrobial peptide melittin and its retro isomer for efficient
      gene transfection.
AB  - A crucial bottleneck in nonviral vector-mediated gene delivery is poor endosomal
      escape. Here, we constructed novel gene vectors by coupling the stearyl moiety to
      the N-terminus of the antimicrobial peptide melittin (stearyl-Mel) and its retro
      isomer (stearyl-rMel) due to their high membrane-lytic activity. As expected,
      stearyl-Mel showed obvious increases in endosome-lytic activity and transfection
      efficiency compared with the reported stearyl-TP10. More gratifyingly, the
      transfection efficiency of stearyl-rMel was around 10-fold greater than that of
      stearyl-Mel and almost reached the transfection levels of Lipofectamine 2000 due
      to the enhanced endosome-lytic activity. Furthermore, the stearyl-rMel/p53
      plasmid complex exhibited higher p53 expression and antitumor activity than
      stearyl-Mel, confirming the fact that stearyl-rMel displayed higher transfection
      efficiency. Taken together, the combination of the stearyl moiety with retro
      melittin provides a novel framework for the development of excellent nonviral
      gene vectors. 

PMID- 24107138
TI  - Influence of equatorial and axial carboxylato ligands on the kinetic inertness of
      platinum(IV) complexes in the presence of ascorbate and cysteine and within DLD-1
      cancer cells.
AB  - The rapid and premature reduction of platinum(IV) complexes in vivo is a
      significant impediment to these complexes being successfully employed as
      anticancer prodrugs. This study investigates the influence of the platinum(IV)
      coordination sphere on the ease of reduction of the platinum center in various
      biological contexts. In the presence of the biological reductants, ascorbate and
      cysteine, platinum(IV) complexes with dicarboxylato equatorial ligands were
      observed to exhibit lower reduction potentials and slower reduction rates than
      analogous platinum(IV) complexes with dichlorido equatorial ligands.
      Diaminetetracarboxylatoplatinum(IV) complexes exhibited unusually long half-lives
      in the presence of excess reductants; however, the complexes exhibited moderate
      potency in vitro, indicative of rapid reduction within the intracellular
      environment. By use of XANES spectroscopy, trans-[Pt(OAc)2(ox)(en)] and trans
      [PtCl2(OAc)2(en)] were observed to be reduced at a similar rate within DLD-1
      cancer cells. This large variability in kinetic inertness of
      diaminetetracarboxylatoplatinum(IV) complexes in different biological contexts
      has significant implications for the design of platinum(IV) prodrugs. 

PMID- 24107139
TI  - Lamivudine resistance leading to de novo hepatitis B infection in recipients of
      hepatitis B core antibody positive liver allografts.
AB  - Most studies have shown that lamivudine (LAM) prophylaxis is sufficient to
      prevent hepatitis B virus (HBV) transmission in recipients of hepatitis B core
      antibody positive (HBcAb(+) ) allografts. However, de novo hepatitis B (DNHB) is
      known to occur in this patient population. Herein, we report a case series of
      four liver transplant recipients who developed DNHB after receiving HBcAb(+)
      allografts due to acquisition of LAM resistance mutations, suggesting that LAM
      prophylaxis may be suboptimal. A retrospective chart review was performed of all
      adult liver transplants performed at Mount Sinai from 2001 to 2010. A total of 79
      patients received HBcAb(+) allografts for non-hepatitis B-related liver disease.
      Of these 79 recipients, four patients developed DNHB and were found to have
      documented LAM resistance. With the increasing use of HBcAb(+) donor livers, we
      suspect that there will also be a growing number of cases of DNHB due to
      acquisition of LAM resistance. We suggest that other agents, such as entecavir or
      tenofovir, be considered for use as prophylaxis in this patient population to
      decrease this risk. 

PMID- 24107140
TI  - Estimating the U.S. prevalence of chronic obstructive pulmonary disease using pre
      and post-bronchodilator spirometry: the National Health and Nutrition
      Examination Survey (NHANES) 2007-2010.
AB  - BACKGROUND: During 2007-2010, the National Health and Nutrition Examination
      Survey (NHANES) conducted a spirometry component which obtained pre
      bronchodilator pulmonary lung function data on a nationally representative sample
      of US adults aged 6-79 years and post-bronchodilator pulmonary lung function data
      for the subset of adults with airflow limitation. The goals of this study were to
      1) compute prevalence estimates of chronic obstructive pulmonary disease (COPD)
      using pre-bronchodilator and post-bronchodilator spirometry measurements and
      fixed ratio and lower limit of normal (LLN) diagnostic criteria and 2) examine
      the potential impact of nonresponse on the estimates. METHODS: This analysis was
      limited to those aged 40-79 years who were eligible for NHANES pre-bronchodilator
      spirometry (n=7,104). Examinees with likely airflow limitation were further
      eligible for post-bronchodilator testing (n=1,110). Persons were classified as
      having COPD based on FEV1/FVC < 70% (fixed ratio) or FEV1/FVC < lower limit of
      normal (LLN) based on person's age, sex, height, and race/ethnicity. Those
      without spirometry but self-reporting both daytime supplemental oxygen therapy
      plus emphysema and/or current chronic bronchitis were also classified as having
      COPD. The final analytic samples for pre-bronchodilator and post-bronchodilator
      analyses were 77.1% (n=5,477) and 50.8% (n=564) of those eligible, respectively.
      To account for non-response, NHANES examination weights were adjusted to the
      eligible pre-bronchodilator and post-bronchodilator subpopulations. RESULTS: In
      2007-2010, using the fixed ratio criterion and pre-bronchodilator test results,
      COPD prevalence was 20.9% (SE 1.1) among US adults aged 40-79 years. Applying the
      same criterion to post-bronchodilator test results, prevalence was 14.0% (SE
      1.0). Using the LLN criterion and pre-bronchodilator test results, the COPD
      prevalence was 15.4% (SE 0.8), while applying the same criterion to post
      bronchodilator test results, prevalence was 10.2% (SE 0.8). CONCLUSIONS: The
      overall COPD prevalence among US adults aged 40-79 years varied from 10.2% to
      20.9% based on whether pre- or post-bronchodilator values were used and which
      diagnostic criterion (fixed ratio or LLN) was applied. The overall prevalence
      decreased by approximately 33% when airflow limitation was based on post
      bronchodilator as compared to pre-bronchodilator spirometry, regardless of which
      diagnostic criterion was used.

PMID- 24107143
TI  - In vitro antioxidant and antiproliferative activities of 5-hydroxymethylfurfural.
AB  - 5-HMF is widely presented in foods and produced through the degradation of
      hexoses and Maillard reaction during heat treatment of foods containing reducing
      sugars and amino acids in an acid environment. However, controversial conclusions
      on the biological effects of 5-HMF have been drawn in previous studies.
      Therefore, the main aim of this study was to investigate the antioxidant and
      antiproliferative activities of 5-HMF. The 2,2'-azinobis-3-ethylbenzothiazolin-6
      sulfonic acid (ABTS) assay, the 1,1-diphenyl-2-picryhydrazyl (DPPH) assay, and
      the hemolysis assay induced by 2,2'-azobis(2-amidinopropane) dihydrochloride
      (AAPH) were performed to evaluate the antioxidant capacity of 5-HMF. The results
      showed that 5-HMF exhibited novel antioxidant activity by scavenging the ABTS and
      DPPH free radicals and inhibited the AAPH-induced hemolysis in a dose-dependent
      manner. In the hemolysis assay, the reduction of ROS and MDA contents and the
      increase in enzyme activities of SOD, CAT, and GPx were found in erythrocytes
      pretreated with 5-HMF, which demonstrated that 5-HMF could prevent the
      peroxidation from the source to protect the erythrocytes. The morphological
      changes of erythrocytes was also verified by observation using atomic force
      microscopy. The inhibitory effect of 5-HMF on human cancer cell proliferation was
      investigated by MTT assay, flow cytometric analysis, and the TUNEL and DAPI
      costaining assay. The results showed that 5-HMF displayed higher
      antiproliferative activity on human melanoma A375 cells than other cell lines.
      Further investigation on the action mechanisms revealed that 5-HMF could induce
      A375 cell apoptosis and G0/G1 cell cycle arrest. The A375 cell apoptosis that 5
      HMF induced was characterized by a TUNEL and DAPI costaining assay. These
      findings suggest that 5-HMF could be developed as a novel natural antioxidant
      with potential applications in cancer chemoprevention. 

PMID- 24107144
TI  - Simple catalytic mechanism for the direct coupling of alpha-carbonyls with
      functionalized amines: a one-step synthesis of Plavix.
AB  - The direct alpha-amination of ketones, esters, and aldehydes has been
      accomplished via copper catalysis. In the presence of catalytic copper(II)
      bromide, a diverse range of carbonyl and amine substrates undergo fragment
      coupling to produce synthetically useful alpha-amino-substituted motifs. The
      transformation is proposed to proceed via a catalytically generated alpha-bromo
      carbonyl species; nucleophilic displacement of the bromide by the amine then
      delivers the alpha-amino carbonyl adduct while the catalyst is reconstituted. The
      practical value of this transformation is highlighted through one-step syntheses
      of two high-profile pharmaceutical agents, Plavix and amfepramone. 

PMID- 24107145
TI  - A pilot phase II study of the efficacy and biosafety of doxorubicin chemotherapy
      in tumor-bearing equidae.
AB  - BACKGROUND: The efficacy and biosafety of a previously established tolerable
      dosage of doxorubicin have not been established in horses. OBJECTIVES: To provide
      preliminary evidence of the efficacy of doxorubicin in tumor-bearing horses,
      explore drug pharmacokinetics profile, and estimate period of risk of exposure to
      drug residues. ANIMALS: Twelve horses with 37 tumors. PROCEDURES: Treatment
      protocol included 6 treatments at 3-week intervals. Eight horses were uniformly
      treated at a dosage of 70 mg/m(2) and 4 horses received 4 of 6 treatment cycles
      at 70 mg/m(2) . Clinical signs, tumor responses, and toxicoses were evaluated.
      Drug residue concentrations were quantitated in 3 horses receiving of 65, 70, and
      75 mg/m(2) by high-performance liquid chromatography with ultraviolet detection
      (plasma, feces) and liquid chromatography and tandem mass spectrometry (urine).
      RESULTS: Thirty tumors, including lymphomas, carcinomas, sarcoids, and melanoma,
      were evaluated for efficacy. The overall response rate was 47% (95% CI, 28-65%).
      Doxorubicin was not found to be effective against melanomas. Lymphomas and
      carcinomas were most responsive. Pooled serum Cmax and half-life of doxorubicin
      were 121.3 ng/mL and 12.9 hours, respectively. There were no detectable residues
      in fecal samples up to 3 weeks after treatment and in plasma and urine after 2
      and 3 days, respectively. CONCLUSION AND CLINICAL RELEVANCE: This study provides
      preliminary evidence that single-agent doxorubicin at a dosage of 70 mg/m(2) has
      a broad spectrum of activity. The risk of exposure to drug residues in plasma and
      feces was low. Direct contact with urine-contaminated wastes should be avoided
      for 2 days after treatment.

PMID- 24107146
TI  - Disease of the year: juvenile idiopathic arthritis--differential diagnosis.
AB  - PURPOSE: The purpose of this review is to comprehensively explain the
      differential diagnosis of juvenile idiopathic arthritis-associated uveitis.
      METHODS: Web-based literature review. RESULTS: Main diagnostic decisions are made
      through a thorough anterior segment exam and a comprehensive exploration of past
      medical and family history. CONCLUSIONS: High clinical suspicion of other uveitic
      entities occurring in children is necessary and must be excluded by the
      practitioner before immediate diagnosis of juvenile idiopathic arthritis is made.

PMID- 24107147
TI  - Activation of non-sensitizing or low-sensitizing fragrance substances into potent
      sensitizers - prehaptens and prohaptens.
AB  - Experimental and clinical studies have shown that fragrance substances can act as
      prehaptens or prohaptens. They form allergens that are more potent than the
      parent substance by activation outside or in the skin via abiotic (chemical and
      physical factors) and/or biotic activation, thus, increasing the risk of
      sensitization. In the present review a series of fragrance substances with well
      documented abiotic and/or biotic activation are given as indicative and
      illustrative examples of the general problem. Commonly used fragrance substances,
      also found in essential oils, autoxidize on contact with air, forming potent
      sensitizers that can be an important source for contact allergy to fragrances and
      fragranced products. Some of them can act as prohaptens and be activated in the
      skin as well. The experimental findings are confirmed in large clinical studies.
      When substances with structural alerts for acting as prohaptens and/or prehaptens
      are identified, the possibility of generating new potent allergens should be
      considered. Predictive testing should include activation steps. Further
      experimental and clinical research regarding activation of fragrance substances
      is needed to increase consumer safety.

PMID- 24107148
TI  - New multi-ferrocenyl- and multi-ferricenyl- materials via coordination-driven
      self-assembly and via charge-driven electro-crystallization.
AB  - Three new tetra-ferrocenylethynylpyridinyl copper complexes, L4(CuI)4 (3),
      L4(CuBr)2 (4), and L4(CuCl)2 (5) have been prepared from the reaction of
      ferrocenylethynylpyridine (L)(2) with copper halides CuX (with X = I(-), Br(-),
      Cl(-)).The ligand 2 and the complexes 3-5 have been fully characterized by
      spectroscopic methods. The structures of 2-4 have been confirmed by single
      crystal X-ray crystallography. 2 forms a dimer in the crystalline-state through C
      H..N hydrogen bonds. 4 and 5 are dimers and 3 a tetramer, in all cases linked
      through Cu-X..Cu bridging interactions. Cyclic voltammetry in dichloroethane
      showed chemically reversible multiferrocenyl oxidation signals with evidence for
      product electro-crystallization. The oxidation products were isolated by
      electrodeposition onto a Pt disc electrode and investigated by scanning electron
      microscopy which confirmed the spontaneous formation of crystalline oxidation
      products with distinctive morphologies. Energy dispersive X-ray elemental
      analysis shows the presence of hexafluorophosphate (counterion) with the P:Fe
      ratio of 1:1, 0.5:1, and 1:1 for the electrocrystallized products 3, 4, and 5,
      respectively, suggesting the formulas [3](4+)(PF6(-))4, [4](2+)(PF6(-))2, and
      [5](4+)(PF6(-))4 for the electro-crystallized products. 

PMID- 24107149
TI  - Second trimester maternal serum inhibin-A in fetal anemia secondary to hemoglobin
      Bart's disease.
AB  - OBJECTIVE: To compare the levels of inhibin-A between pregnancies with fetal
      anemia secondary to Hb Bart's disease and pregnancies with normal non-anemic
      fetuses. METHODS: Sixty-five pregnancies at risk of fetal Hb Bart's disease
      scheduled for cordocentesis at 18-22 weeks were prospectively recruited into the
      study. Inhibin-A levels were measured from maternal blood drawn before
      cordocentesis. Fetal blood samples were collected for fetal Hb typing and
      hemoglobin (Hb) levels. RESULTS: Maternal serum inhibin-A was significantly
      higher in women with fetal Hb Bart's disease than those with unaffected fetuses
      (1.03 MoM (multiple of median) and 0.75 MoM, respectively, p = 0.001). The
      relationship between maternal serum inhibin-A and fetal Hb level was a quadratic
      equation; inhibin-A = 5.248 - 9.415(Hb) + 4.919(Hb)(2) (r(2) = 0.274, p < 0.001).
      Maternal serum inhibin-A did not correlate with cardiomegaly but was
      significantly associated with placental thickness; inhibin-A = 1.372 - 0.751(Pl)
      + 0.214(Pl)(2) (r(2) = 0.237, p = 0.007). CONCLUSIONS: Maternal serum inhibin-A
      levels were significantly higher in pregnancies with fetal Hb Bart's disease. The
      elevation of inhibin-A was likely to be a consequence of fetal anemia and
      placentomegaly. Since inhibin-A is commonly used as a component of quadruple
      test; the calculated risk of Down's syndrome may be unreliable in pregnancies
      with fetal Hb Bart's disease or possible fetal anemia.

PMID- 24107150
TI  - Towards improved uptake of malaria chemoprophylaxis among West African
      travellers: identification of behavioural determinants.
AB  - BACKGROUND: Malaria is a potentially lethal illness for which preventive measures
      are not optimally used among all travellers. Travellers visiting friends and
      relatives in their country of origin (VFRs) are known to use chemoprophylaxis
      less consistently compared to tourist travellers. In this study, factors
      explaining the low use of chemoprophylaxis were pursued to contribute to
      improving uptake of preventive measures among VFRs. METHODS: Following in-depth
      interviews with Ghanaians living in Amsterdam, a questionnaire was developed to
      assess which behavioural determinants were related to taking preventive measures.
      The questionnaire was administered at gates of departing flights from Schiphol
      International Airport, Amsterdam (the Netherlands) to Kotoka International
      Airport, Accra (Ghana). RESULTS: In total, 154 questionnaires were eligible for
      analysis. Chemoprophylaxis had been started by 83 (53.9%) and bought by 93
      (60.4%) travellers. Pre-travel advice had been obtained by 104 (67.5%)
      travellers. Those who attended the pre-travel clinic and those who incorrectly
      thought they had been vaccinated against malaria were more likely to use
      preventive measures. Young-, business- and long-term travellers, those who had
      experienced malaria, and those who thought curing malaria was easier than taking
      preventive tablets were less likely to use preventive measures. CONCLUSION:
      Almost half of the VFRs travelling to West Africa had not started
      chemoprophylaxis; therefore, there is room for improvement. Risk reduction
      strategies could aim at improving attendance to travel clinics and focus on young
      , business and long term travellers and VFRs who have experienced malaria during
      consultation. Risk reduction strategies should focus on improving self-efficacy
      and conceptions of response efficacy, including social environment to aim at
      creating the positive social context needed.

PMID- 24107152
TI  - [Cyclins D in regulation and dysregulation of the cell cycle in multiple
      myeloma].
AB  - Multiple myeloma is the second most common hematooncological disease
      characterized by clonal proliferation of plasma cells and monoclonal
      immunoglobulin production. It is a heterogenous disease; however, dysregulation
      of cyclins D seems to be an early unifying pathogenic event in multiple myeloma.
      In almost all patients, there is increased expression level of at least one of
      the cyclins D. Nevertheless, the mechanism of this increase is unknown in many
      cases. Next to wellknown roles of cyclins D in the cell cycle, they have many
      other functions contributing to tumor cell progression. Cyclins D are prognostic
      markers and are also used for subclassification of multiple myeloma. In this
      review, we focus on significance of cyclins D in multiple myeloma.

PMID- 24107153
TI  - [The reasons of changes in revised staging for carcinoma of the vulva].
AB  - BACKGROUND: Review of revised staging system for vulva, explaining the changes of
      staging and their impact on the prognosis of disease is presented. AIM: The main
      objectives of a reliable staging system include an assessment of prognosis,
      planning treatment, and the evaluation of their outcomes. A good staging system
      must meet three basic characteristics: validity, reliability and practicality.
      Since medical research and practice in the field of oncology have shown explosive
      growth, the staging of vulvar cancer and some other cancers did not give a good
      spread of prognostic groupings. Changes based on new findings were proposed in
      2008 by the FIGO Committee on Gynecologic Oncology, approved, and published a
      year later the changes in the staging system for carcinoma of the vulva. Stage 0
      was deleted, since it represents preinvasive lesion. Stage IA remained unchanged
      and stage I and II were combined. The number and morphology of the involved nodes
      were taken into account, and the bilaterality of positive nodes has been
      discounted. CONCLUSION: The purpose of a good staging system is to offer a
      classification of the extent of gynecological cancer, in order to provide a
      method of conveying ones clinical experience to others for the comparison of
      different treatment methods. As a result of the explosion of medical research in
      the field of oncology, the staging of some of the gynecological cancers became
      outdated and did not give a good spread of prognostic groupings. According to the
      revised staging for carcimona of the vulva, patients are divided to groups with
      similar prognosis. Therefore, exchange of relevant information between
      oncological centers is facilitated, thus disseminating knowledge and stimulating
      research in other parts of the world.

PMID- 24107154
TI  - [Management of infections in palliative and terminal cancer care].
AB  - BACKGROUND: Patients with cancer are highly susceptible to infections. There is a
      lack of evidencebased guidelines or protocols for their management in palliative
      and endoflife care. PURPOSE: To define an optimal dia-gnostic approach and
      therapeutic management of infections in patients with palliative and terminal
      cancer care. Along with thromboembolic disease and cancer progression, infections
      are the most frequent causes of death in oncology. Besides the impact on
      mortality, they are accompanied with a myriad of symptoms decreasing the quality
      of life. High incidence of infectons is due to a malignancy itself, the
      oncolgical therapy and host factors. There is a lack of evidencebased guidelines
      and protocols for the therapy of infections in palliative and terminal cancer
      care. Most of available studies are retrospective in nature, with diverse methods
      and cohorts. Incidence of infections in these patient oscillates between 16- 55%
      in specialized palliative units, and rises up to 83% in acute care hospitals.
      From the epidemiologic viewpoint, urinary (39- 42%) and respiratory infections
      (22- 36%) are the most frequent cases, followed by soft tissue and skin
      infections (6- 12%) and bacteremias (5- 14%). At present, the antibio-tic
      treatment does not seem to have a positive impact on the survival rate. Symptom
      control antibio-tic therapy as a means of symptom control still remains
      controversial, since it meets this purpose only in a few percents of studies. The
      most successful is the symtom control in urinary tract infections (60- 79%), in
      contrast to other sites of infection (30- 43%). In the last week of life there
      the symptom control is achieved only in 10% of patient. One should always
      consider the prognosis, actual preformance status and patients preferences when
      it comes to the management of dia-gnostics and therapy of infections. If the
      prognosis counts in weeks or months the dia-gnostics and therapy should not
      differ from the approach to any other oncological patient. In terminal cancer
      care the antibio-tics should be spared strictly for the purpose of symptom
      control and with a palliative intent. This article reviews current knowledge of
      dia-gnostics and therapy of infections in palliative cancer care and includes an
      algorithm for their management.

PMID- 24107155
TI  - Proliferation activity in the adult rat brain following exposure to ionizing
      radiation.
AB  - BACKGROUND: The aim of our study was to investigate radiationinduced shortterm
      effects on the rat forebrain. MATERIAL AND METHODS: Adult male Wistar rats
      received whole body exposure with fractionated doses of gamma rays (a total dose
      of 3 Gy) and were investigated seven and 14 days later. Immunohistochemistry and
      confocal microscopy were used to determine proliferating cells derived from
      anterior subventricular zone (SVZa) and distributed along the subventricular zone
      olfactory bulb axis (SVZ OB axis). Cell counting was performed in four anatomical
      parts along the welldefined pathway, known as the rostral migratory stream (RMS)
      represented by the SVZa, vertical arm, elbow and horizontal arm. RESULTS:
      Different rate of cell overdistribution was found in all counted parts through
      the entire experiment, mostly detectable in the elbow and horizontal arm.
      CONCLUSION: Results suggested that radiation response of proliferating cells
      resides the SVZa may a play contributory role in the development of more adverse
      radiationinduced: late effects.

PMID- 24107156
TI  - [Nephroblastoma -  30-years period of its treatment in the University Hospital
      Motol, Prague].
AB  - INTRODUCTION: Nephroblastoma (Wilms tumor - WT) is the most common solid tumor of
      kidney in children. We present treatment development of WT at the Department of
      Pediatric Hematology and Oncology, Charles University in Prague, 2nd Faculty of
      Medicine and University Hospital Motol (KDHO) in the Czech Republic over 30
      years. Patients that were treated prior to access to the International Society of
      Pediatric Oncology (SIOP) protocols are considered to be the historical group,
      then we have patients treated according to SIOP 9, SIOP 93-01 and SIOP 2001
      protocols as full participants of SIOP studies. PATIENTS AND METHODS: Between
      January 1980 and April 2009, we treated 330 patients with WT at KDHO: 91 patients
      in historical group (1980-1988), 94 pts in SIOP 9 (1988-1993), 80 pts in SIOP 93
      01 (1994-2001) and 65 pts in SIOP 2001 (2002-2009). Overall survival (OS) and
      event-free survival (EFS) were analyzed by Kaplan-Meier test. RESULTS: The
      overall ten-year EFS was 81.2% and OS 87.6%. Fifty-eight patients from the 330
      (17.6%) had metastases at diagnosis, EFS without metastatic process was 84.6%
      compared to 65.4% with metastasis presented at diagnosis (p = 0.0003), OS was
      70.7% compared to 91.2% (p < 0.0001). One hundred and seventy patients (51.5%)
      were treated with preoperative chemotherapy and/or radiotherapy, whereas 158
      patients (47.5%) underwent primary nephrectomy; EFS and OS did not differ:
      neoadjuvant vs primary nephrectomy EFS was 81.2% vs 80.9% (p = 0.85), OS 89.4% vs
      85.4% (p = 0.38). Sixty (18%) patients experienced disease recurrence; OS after
      relapse was 33%. In the historical group, EFS and OS were 85.7% and 91.2%. In
      patients treated according to the SIOP 9 protocol, EFS and OS were 68.1% and
      74.5%, resp. In patients treated according to SIOP 93-01, it was 83.6% and 93.7%,
      resp. and in patients treated according to 87 SIOP 2001, it was 7% and 95.4% (p =
      0.001 and p = 0.0008), resp. CONCLUSION: WT is a well treatable disease. The aim
      for the future is to maintain the current very good survival while minimizing the
      treatment intensity.

PMID- 24107157
TI  - [Attainment of complete hematological remission is crucial for extended survival
      of AL amyloidosis patients with cardiac involvement].
AB  - BACKGROUND: Symptomatic cardiac involvement is the most important prognostic
      factor in AL amyloidosis patients. Longterm survival is limited not only by
      cardiac involvement condition, but also by limited choice of treatment with
      unsatisfactory results. The aim of the present report is to assess the effect of
      achieved treatment response on survival of AL amyloidosis patients with
      symptomatic cardiac involvement under conventional treatment. MATERIAL AND
      METHODS: The monitored patient set consisted of 19 patients with systemic AL
      amyloidosis and symptomatic cardiac involvement, treated and monitored at the
      III. Clinic of Internal Medicine between 2004 and 2012. The male : female ratio
      was 17 : 2, and the age median was 64 (range 48 to 78 years). Thirteen patients
      died within the monitored period. Functional status was defined according to the
      NYHA classification, where five patients had class II involvement, 10 patients
      had class III involvement, and four patients had class IV involvement. Treatment
      response was assessed by the application of modified IMWG and ISA criteria; all
      patients were undergoing conventional treatment. Nine patients were treated by a
      combination of alkylating agents (alkeran, cyclophosphamide), six were treated by
      a combination treatment with thalidomide, and four were treated by a combination
      of bortezomib and dexamethasone. Data were analyzed with software SPSS v. 15
      (SPSS, Inc., Chicago, USA). Log Rank Test was applied to survival evaluation.
      RESULTS: The statistical analysis included only 13 patients who underwent at
      least three months of treatment, where six patients attained complete remission
      (CR), four patients attained partial remission (PR), and three patients attained
      only stabilization of disease (SD). Significant difference in patient survival
      was found to be correlated with attained hematological response, where the
      patients who attained CR had median survival of 39 months vs 10 months in
      patients who attained PR or SD (p = 0.005). CONCLUSION: The results indicate that
      attainment of complete hematological remission is associated with significantly
      longer survival of AL amyloidosis patients with symptomatic cardiac involvement.

PMID- 24107158
TI  - [The clinical, histopathological and imaging methods characteristics of Non
      Hodgkin lymphomas in patients with brain involvement].
AB  - BACKGROUND: The Non- Hodgkin-lymphoma (NHL) brain infiltration carries a poor
      prognosis. Because of relatively rare incidence, we decided to share our
      experience. PATIENTS AND METHODS: Retrospective analysis of patients with NHL
      brain infiltration dia-gnosed in 2001- 2011 at our university hospital. RESULTS:
      Twenty -seven patients with median age of 61 (range 42- 82) years were analyzed.
      The primary diffuse large cell B cell lymphoma of CNS was defined in 22/ 27 (81%)
      patients, in the others systemic NHL was present. Median positivity of the
      proliferative marker Ki 67 was 80%, the number of NHL lesions 1 (1- 8), diameter
      28 * 30 * 29 (11 * 16 * 20 to 85 * 76 * 65) mm. The fundamental finding in brain
      lymphoma MRI imaging was lesion with predominantly homogenous contrast
      enhancement, diffusion restriction and collateral edema. Thirteen out of 27 (48%)
      patients underwent lumbar puncture, and lymphoma presence in fluid was detected
      in only two of them. The most frequent symptoms were limb paresis or hemiparesis
      (55%), bradypsichysm (22%), expressive aphasia (22%), cephalea (18%).
      Corticosteroid therapy, as a primary treatment option, was indicated in 15% of
      patients with a median overall survival of one month, CNS radiotherapy in 37%
      with a median survival of three months, and chemotherapy in 48% patients with a
      median overall survival 10 (2- 45) months. CONCLUSION: The brain lymphomas are
      rare and prognostically very unfavorable affection. When specifying brain focal
      lesions on MRI, it is necessary to consider this etiology and to elect imaging
      protocols with contrast agents and diffusion weighted sequence. Biopsy should be
      performed prior to start of corticosteroid therapy. Intensive chemotherapy or
      radiotherapy indication must be individually considered, and proposed treatment
      should be initiated immediately with a potential for somewhat prolonged survival.

PMID- 24107159
TI  - [Polyneuropathic pain therapy with a patient suffering from generalized castrate-
      resistant prostate cancer -  clinical case report].
AB  - BACKGROUND: Tapentadol is a u -opioid receptors agonist as well as an inhibitor
      of noradrenaline reuptake. This pharmacologic profile of tapentadol makes it a
      suitable drug of choice in nociceptive and neuropathic pain control. CASE REPORT:
      This clinical report pressents a 65year old man with poorly differentiated
      prostate cancer -  Gleason score 8 (4 + 4) with metastatic bone disease. Besides
      the initial application of bisphosphonates, the patient had been treated with
      androgen deprivation therapy (cyproterone acetate + leuprolide acetate) for the
      period of 18 months. This therapy was terminated due to an increase of PSA
      levels. Subsequently, the patient underwent palliative docetaxelbased
      chemotherapy. There were eight cycles applied with positive clinical and
      laboratory effect. However, the further application was limited by the averse
      effects, namely the peripheral neuropathy manifested by pain in arms and legs.
      The peripheral neuropathy had progressive tendency even after the end of
      chemotherapy, and supportive treatment with gabapentin and amitryptiline failed
      to succeed. Four months after zoledronic acid monotherapy, the patient was
      started on tapentadol in 50-mg dose b.i.d., consequently escalated to 100 mg
      b.i.d. (to this point, 25 ug of transdermal fentanyl were used for pain
      management). Significant relief from neuropathic discomfort was observed three
      weeks from the onset of tapentadol therapy. Patients state of health normalized
      within three months after the initiation of therapy. Consequently, the patient
      was able to receive docetaxel chemotherapy again, without any neuropathic pain
      exacerbation on the maintenance dose of tapentadol 50 mg b.i.d. CONCLUSION:
      Tapentadol administration resulted in stable and longtime relief from neuropathic
      pain which is a frequent side effect in the course of castrate-resistant prostate
      cancer therapy with taxanes.

PMID- 24107160
TI  - [Chylous ascites as a serious complication of the neuroendocrine tumor of ileum -
      case report].
AB  - BACKGROUND: Chylous ascites is a rare complication of the gastrointestinal
      neuroendocrine tumor. There are two mechanisms of its origin: mechanical
      obstruction by the tumor mass and fibrosis of the surrounding tissue due to
      overproduction of serotonin. Its presence restricts treatment options. CASE: We
      report a case of 66year old man suffering from recurrent diarrhoea and ascites.
      We found elevated tumor marker Chromogranin A and elevation of
      hydroxyindoleacetic acid (5- HIAA) in the urine. A subsequent whole body
      scintigraphy scan by octreoscan confirmed multinodal process with increased
      somatostatin receptors activity in the wall of the ileum, rectosigmoideum, lymph
      nodes of the retroperitoneum and mesenterium and left supraclavicular area. We
      performed bio-psy from the lymph node of supraclavicular area, and there was
      metastasis of the neuroendocrine tumor. Start of cytostatic therapy was
      repeatedly complicated by recurrent massive chylous ascites. The patient
      underwent only one series of palliative chemotherapy. Another procedure was again
      complicated by chylous ascites that caused hospitalization at the internal
      department, and the patient died four months after dia-gnosis. CONCLUSION:
      Chylous ascites is a very rare complication of gastrointestinal neuroendocrine
      tumor. It is not only a marker of poor prognosis, but also a complication that
      makes systemic treatment very difficult.

PMID- 24107162
TI  - [Patient with atypical neurocytoma -  case report].
AB  - BACKGROUND: Neurocytoma represents a rare tumor of the central nervous system
      usually slowly growing and generally with good prognosis after surgical resection
      with or without adjuvant radiotherapy. CASE: A 25-year- old woman presented with
      sudden fainting. During the initial workup, brain CT was completed with finding
      of tumor inside the third ventricle spreading into both lateral ventricles. The
      patient underwent partial surgical resection followed by radical gross resection,
      no adjuvant radiotherapy was indicated during the initial treatment and the
      patient was followed up with regular brain MRIs and clinical examinations. Thirty
      six months after the initial resection, there was progression on MRI and
      radiotherapy was recommended. At this moment, patient is 12 months after
      radiotherapy with stable disease on MRI and with good stable performance status.
      CONCLUSION: One of the greatest problems in the management of neurocytoma is the
      timing of adjuvant radiotherapy. From published data, it is clear that adjuvant
      radiotherapy increases local control; however, this has to be considered
      carefully against the possible risks from late side effects of radiotherapy
      considering long-time survival of the patients.

PMID- 24107168
TI  - Network biomarkers reveal dysfunctional gene regulations during disease
      progression.
AB  - Extensive studies have been conducted on gene biomarkers by exploring the
      increasingly accumulated gene expression and sequence data generated from high
      throughput technology. Here, we briefly report on the state-of-the-art research
      and application of biomarkers from single genes (i.e. gene biomarkers) to gene
      sets (i.e. group or set biomarkers), gene networks (i.e. network biomarkers) and
      dynamical gene networks (i.e. dynamical network biomarkers). In particular,
      differential and dynamical network biomarkers are used as representative examples
      to demonstrate their effectiveness in both detecting early signals for complex
      diseases and revealing essential mechanisms on disease initiation and progression
      at a network level. 

PMID- 24107169
TI  - Molecular pathological analysis of sarcomas using paraffin-embedded tissue:
      current limitations and future possibilities.
AB  - Sarcomas of soft tissue and bone are rare neoplasms that can be separated into a
      large number of different diagnostic entities. Over the years, a number of
      diagnostic markers have been developed that aid pathologists in reaching the
      appropriate diagnoses. Many of these markers are sarcoma-specific proteins that
      can be detected by immunohistochemistry in formalin-fixed, paraffin-embedded
      (FFPE) sections. In addition, a wide range of molecular studies have been
      developed that can detect gene mutations, gene amplifications or chromosomal
      translocations in FFPE material. Until recently, most sequencing-based approaches
      relied on the availability of fresh frozen tissue. However, with the advent of
      next-generation sequencing technologies, FFPE material is increasingly being used
      as a tool to identify novel immunohistochemistry markers, gene mutations, and
      chromosomal translocations, and to develop diagnostic tests. 

PMID- 24107170
TI  - What is next after the genes for autoimmunity?
AB  - Clinical pathologies draw us to envisage disease as either an independent entity
      or a diverse set of traits governed by common physiopathological mechanisms,
      prompted by environmental assaults throughout life. Autoimmune diseases are not
      an exception, given they represent a diverse collection of diseases in terms of
      their demographic profile and primary clinical manifestations. Although they are
      pleiotropic outcomes of non-specific disease genes underlying similar
      immunogenetic mechanisms, research generally focuses on a single disease. Drastic
      technologic advances are leading research to organize clinical genomic
      multidisciplinary approaches to decipher the nature of human biological systems.
      Once the currently costly omic-based technologies become universally accessible,
      the way will be paved for a cleaner picture to risk quantification, prevention,
      prognosis and diagnosis, allowing us to clearly define better phenotypes always
      ensuring the integrity of the individuals studied. However, making accurate
      predictions for most autoimmune diseases is an ambitious challenge, since the
      understanding of these pathologies is far from complete. Herein, some pitfalls
      and challenges of the genetics of autoimmune diseases are reviewed, and an
      approximation to the future of research in this field is presented. 

PMID- 24107178
TI  - Advances in adenovirus-mediated p53 cancer gene therapy.
AB  - INTRODUCTION: The tumor suppressor p53 gene regulates diverse cellular processes,
      such as cell-cycle arrest, senescence, apoptosis and autophagy, and it is
      frequently inactivated by genetic alterations in ~ 50% of all types of human
      cancers. To restore wild-type p53 function in p53-inactivated tumors, adenovirus
      mediated p53 gene therapy has been developed as a promising antitumor strategy in
      preclinical experiments and clinical studies. AREAS COVERED: This review focuses
      on the clinical relevance of replication-deficient adenovirus vectors that carry
      the wild-type p53 gene (Ad-p53; Advexin, Gendicine and SCH-58500) in clinical
      studies of patients with various cancers and the future perspectives regarding
      conditionally replicating adenovirus vectors expressing the wild-type p53 gene
      (CRAd-p53; AdDelta24-p53, SG600-p53, OBP-702) in preclinical experiments.
      Moreover, the recent advances in our understanding of the molecular basis for the
      p53-mediated tumor suppression network induced by Ad-p53 and CRAd-p53 vectors and
      the combination therapies for promoting the therapeutic potential of adenovirus
      mediated p53 gene therapy are discussed. EXPERT OPINION: Exploration of the
      molecular mechanism underlying the p53-mediated tumor suppression network and the
      effective strategy for enhancing the p53-mediated cell death signaling pathway
      would provide novel insights into the improvement of clinical outcome in p53
      based cancer gene therapy.

PMID- 24107181
TI  - Anion reduction dominated cathodic limit of metal-free ionic liquid: experimental
      and theoretical proofs.
AB  - The cathodic limit of the electrochemical window in the second-generation ionic
      liquids (composed of air- and water-stable metal-free cations and anions) is
      traditionally believed to be determined by the reduction of the cation. More and
      more exceptions, however, were found in various ionic liquids. In this study, the
      cathodic limit of the electrochemical window in 1-butyl-1-methylpyrrolidinium
      salicylate ionic liquid (BMP-SAL IL) was studied. It has been found that the
      cathodic limit of BMP-SAL is determined by the reduction of SAL(-) anion rather
      than the reduction of BMP(+) cation. The cyclic voltammetric behavior, NMR
      spectra, and MALDI-TOF MS spectra of BMP-SAL recorded before and after the IL was
      electrolyzed at the cathodic limit provide sufficient evidence that the major
      reaction at the cathodic limit of BMP-SAL is the reduction of SAL(-) anion. The
      theoretical calculations support the experimental data, and the results indicate
      that anion reduction dominated cathodic limit should be a common phenomenon in
      ionic liquids. 

PMID- 24107180
TI  - Identification of dengue fever cases in Houston, Texas, with evidence of
      autochthonous transmission between 2003 and 2005.
AB  - Houston, Texas, maintains an environment conducive to dengue virus (DENV)
      emergence; however, surveillance is passive and diagnostic testing is not readily
      available. To determine if DENV is present in the area, we tested 3768 clinical
      specimens (2138 cerebrospinal fluid [CSF] and 1630 serum) collected from patients
      with suspected mosquito-borne viral disease between 2003 and 2005. We identified
      47 immunoglobulin M (IgM)-positive dengue cases, including two cases that were
      positive for viral RNA in serum for dengue serotype 2. The majority of cases did
      not report any history of travel outside the Houston area prior to symptom onset.
      The epidemic curve suggests an outbreak occurred in 2003 with continued low-level
      transmission in 2004 and 2005. Chart abstractions were completed for 42 of the 47
      cases; 57% were diagnosed with meningitis and/or encephalitis, and 43% met the
      case definition for dengue fever. Two of the 47 cases were fatal, including one
      with illness compatible with dengue shock syndrome. Our results support local
      transmission of DENV during the study period. These findings heighten the need
      for dengue surveillance in the southern United States.

PMID- 24107182
TI  - Bacterial and heterotrophic nanoflagellate densities and C-biomass estimates
      along an Alaskan tundra transect with prediction of respiratory CO2 efflux.
AB  - Although tundra terrestrial ecology is significantly affected by global warming,
      we know relatively little about how eukaryotic microbial communities respond and
      how much microbial respiratory CO(2) may be released due to available organic
      nutrient sources in the permafrost melt. Prior research has shown a strong
      positive correlation between bacteria and fungi in some Arctic locales; this
      research focused on the relationships of terrestrial bacteria and heterotrophic
      nanoflagellates. The densities and estimated C-biomass of bacteria and
      heterotrophic nanoflagellates (a major occurring group of protozoa) were assessed
      in 14 samples obtained along a 10 km transect in northwest AK during the summer
      of 2012. Two samples were taken, one at the top and one near the base of seven
      hummocks along the transect. Densities (no./g soil) of bacteria varied from 2.7
      16 * 10(9), and nanoflagellates 0.7-7.9 * 10(7). C-biomass (MUg/g soil) of
      bacteria varied from 358 to 2,114, and nanoflagellates 12-37. Additionally, the
      rate of respiration was analyzed in the laboratory for each soil sample. A linear
      relationship between soil respiration and bacterial densities was obtained (20 
      degrees C): R(s) = 12.32 + 14.07 Bd (p ? 0.01); where R(s) is soil respiration
      (nmol/min/g soil) and B(d) = bacterial density (no. * 10(9) /g soil).

PMID- 24107183
TI  - Caspase-1 activity in microglia stimulated by pro-inflammagen nanocrystals.
AB  - Although caspase-1 is a key participant in inflammation, there is no sensitive
      assay to measure its enzymatic activity in real time in cells or animals. Here we
      describe a nanosensor for caspase-1 ratiometric measurements, consisting of a
      rhodamine-labeled, caspase-1 cleavable peptide linked to quantum dots (QDs).
      Microglia cells were stimulated by lipopolysaccharide (LPS) and by hybrid
      nanoparticles LPS-QDs. These stimuli activated caspase-1 in microglia monolayers
      and in the mouse brain, while a selected caspase inhibitor markedly reduced it.
      LPS-QDs entered into the lysosomal compartment and led to an enlargement of these
      cellular organelles in the exposed microglia. Both lysosomal swelling and
      mitochondrial impairment contributed to caspase-1 activation and to the
      consequent interleukin-1beta release. The results from these studies highlight
      how the unique properties of QDs can be used to create versatile biotools in the
      study of inflammation in real time in vivo. 

PMID- 24107184
TI  - RipD (Rv1566c) from Mycobacterium tuberculosis: adaptation of an NlpC/p60 domain
      to a non-catalytic peptidoglycan-binding function.
AB  - Enzymes carrying NlpC/p60 domains, for instance RipA and RipB from Mycobacterium
      tuberculosis, are bacterial peptidoglycan hydrolases that cleave the peptide
      stems and contribute to cell wall remodelling during cell division. A member of
      this protein family, RipD (Rv1566c) from M. tuberculosis described in the present
      study, displays sequence alterations in the NlpC/p60 catalytic triad and carries
      a pentapeptide repeat at its C-terminus. Bioinformatics analysis revealed RipD
      like proteins in eleven mycobacterial genomes, whereas similar pentapeptide
      repeats occur in cell-wall-localized bacterial proteins and in a
      mycobacteriophage. In contrast with previously known members of the NlpC/p60
      family, RipD does not show peptidoglycan hydrolase activity, which is consistent
      with the sequence alterations at the catalytic site. A strong interaction of the
      catalytically inactive core domain with peptidoglycan is however retained,
      presenting the first example of the NlpC/p60 domains that evolved to a non
      catalytic peptidoglycan-binding function. Full-length RipD carrying the C
      terminal repeat shows, however, a decrease in binding affinity to peptidoglycan,
      suggesting that the C-terminal tail modulates the interaction with bacterial cell
      wall components. The pentapeptide repeat at the C-terminus does not adopt a
      defined secondary structure in solution which is in accordance with results from
      the 1.17 A (1 A=0.1 nm) crystal structure of the protein carrying two repeat
      units.

PMID- 24107185
TI  - Gender differences in sagittal standing alignment before pubertal peak growth:
      the importance of subclassification and implications for spinopelvic loading.
AB  - The aim of this study was to analyze gender differences in sagittal standing
      alignment at pre-peak height velocity age thereby applying a scientifically sound
      and practically oriented classification scheme for overall standing balance. The
      study population consisted of healthy boys (n = 639) and girls (n = 557) before
      pubertal peak growth. During subjects' habitual standing, sagittal plane measures
      of the spine, pelvis and lower limbs were collected using a clinical screening
      protocol. With each subject classified as one of three postural types (neutral,
      sway-back, or leaning-forward), differences in sagittal plane alignment were
      analyzed between sexes. The results revealed clear differences between genders in
      each of the postural types. Within the neutral and sway-back postural subgroups,
      boys presented more forward inclination of the trunk, more thoracic kyphosis and
      more pelvis backtilt compared with girls. Within the leaning-forward category,
      girls displayed more forward trunk lean, less thoracic kyphosis and more pelvic
      anteversion. A state of lumbar segmental hyperextension appeared to exist in
      female leaning-forward subjects. Our results reveal for the first time that
      sagittal standing alignment is different between prepubescent boys and girls when
      subjects are appropriately subclassified, and conversely represent a 'wash-out
      effect' when pooled. When the classification system is applied, gender
      specificity in gravity line position is suggested, implying gender-related
      differences in lever arms and thus load. Present findings may add to our
      understanding of gender-specific biomechanical challenges posed by habitual
      posture, and may shed new light on sagittal standing alignment as a possible
      contributory factor in developmental spinal-pelvic disorders. 

PMID- 24107186
TI  - Self-assembled molecular platforms for bacteria/material biointerface studies:
      importance to control functional group accessibility.
AB  - Highly controlled mixed molecular layers are crucial to study the role of
      material surface chemistry in biointerfaces, such as bacteria and subsequent
      biofilms interacting with biomaterials. Silanes with non-nucleophilic functional
      groups are promising to form self-assembled monolayers (SAMs) due to their low
      sensitivity to side-reactions. Nevertheless, the real control of surface
      chemistry, layer structure, and organization has not been determined. Here, we
      report a comprehensive synthesis and analysis of undecyltrichlorosilane- and 11
      bromoundecyltrichlorosilane-based mixed SAMs on silicon substrates. The impact of
      the experimental conditions on the control of surface chemistry, layer structure,
      and organization was investigated by combining survey and high-resolution X-ray
      photoelectron spectroscopy analysis, wettability measurements, and ellipsometry.
      The most appropriate conditions were first determined for elaborating highly
      reproducible, but easily made, pure 11-bromoundecyltrichlorosilane SAMs. We have
      demonstrated that the control is maintained on more complex surfaces, i.e.,
      surfaces revealing various chemical densities, which were obtained with different
      ratios of undecyltrichlorosilane and 11-bromoundecyltrichlorosilane. The control
      is also maintained after bromine to amine group conversion via SN2 bromine-to
      azide reactions. The appropriateness of such highly controlled amino- and methyl
      group revealing platforms (NH2-X%/CH3) for biointerface studies was shown by the
      higher reproducibility of bacterial adhesion on NH2-100%/CH3 SAMs compared to
      bacterial adhesion on molecular layers of overall similar surface chemistry but
      less control at the molecular scale. 

PMID- 24107188
TI  - Longin and GAF domains: structural evolution and adaptation to the subcellular
      trafficking machinery.
AB  - Endomembrane trafficking is one of the most prominent cytological features of
      eukaryotes. Given their widespread distribution and specialization, coiled-coil
      domains, coatomer domains, small GTPases and Longin domains are considered
      primordial 'building blocks' of the membrane trafficking machineries. Longin
      domains are conserved across eukaryotes and were likely to be present in the Last
      Eukaryotic Common Ancestor. The Longin fold is based on the alpha-beta-alpha
      sandwich architecture and a unique topology, possibly accounting for the special
      adaptation to the eukaryotic trafficking machinery. The ancient Per ARNT Sim
      (PAS) and cGMP-specific phosphodiesterases, Adenylyl cyclases and FhlA (GAF)
      family domains show a similar architecture, and the identification of prokaryotic
      counterparts of GAF domains involved in trafficking provides an additional
      connection for the endomembrane system back into the pre-eukaryotic world.
      Proteome-wide, comparative bioinformatic analyses of the domains reveal three
      binding regions (A, B and C) mediating either specific or conserved protein
      protein interactions. While the A region mediates intra- and inter-molecular
      interactions, the B region is involved in binding small GTPases, thus providing
      an evolutionary connection among major building blocks in the endomembrane
      system. Finally, we propose that the peculiar interaction surface of the C region
      of the Longin domain allowed it to extensively integrate into the endomembrane
      trafficking machinery in the earliest stages of building the eukaryotic cell. 

PMID- 24107187
TI  - Anxiety and depression disorders in patients with pulmonary arterial hypertension
      and chronic thromboembolic pulmonary hypertension.
AB  - BACKGROUND: The objective of this prospective study was to assess the prevalence
      of anxiety and depression disorders and their association with quality of life
      (QoL), clinical parameters and survival in patients with pulmonary hypertension
      (PH). METHODS: We prospectively assessed 158 patients invasively diagnosed with
      pulmonary arterial hypertension (n = 138) and inoperable chronic thromboembolic
      PH (n = 20) by clinical measures including quality of life (QoL, SF-36
      questionnaire), cardiopulmonary exercise testing and six minute walking distance
      and by questionnaires for depression (PHQ-9) and anxiety (GAD-7). According to
      the results of the clinical examination and the questionnaires for mental
      disorders (MD) patients were classified into two groups, 1) with moderate to
      severe MD (n = 36, 22,8%), and 2) with mild or no MD (n = 122). Patients were
      followed for a median of 2.7 years. Investigators of QoL, SF-36 were blinded to
      the clinical data. RESULTS: At baseline the 2 groups did not differ in their
      severity of PH or exercise capacity. Patients with moderate to severe MD (group
      1) had a significantly lower QoL shown in all subscales of SF-36 (p < 0.002). QoL
      impairment significantly correlated with the severity of depression (p < 0.001)
      and anxiety (p < 0.05). During follow-up period 32 patients died and 3 were lost
      to follow-up. There was no significant difference between groups regarding
      survival. Only 8% of the patients with MD received psychopharmacological
      treatment. CONCLUSION: Anxiety and depression were frequently diagnosed in our
      patients and significantly correlated with quality of life, but not with long
      term survival. Further prospective studies are needed to confirm the results.

PMID- 24107189
TI  - A systematic review of income generation interventions, including microfinance
      and vocational skills training, for HIV prevention.
AB  - Income generation interventions, such as microfinance or vocational skills
      training, address structural factors associated with HIV risk. However, the
      effectiveness of these interventions on HIV-related outcomes in low- and middle
      income countries has not been synthesized. The authors conducted a systematic
      review by searching electronic databases from 1990 to 2012, examining secondary
      references, and hand-searching key journals. Peer-reviewed studies were included
      in the analysis if they evaluated income generation interventions in low- or
      middle-income countries and provided pre-post or multi-arm measures on
      behavioral, psychological, social, care, or biological outcomes related to HIV
      prevention. Standardized forms were used to abstract study data in duplicate and
      study rigor was assessed. Of the 5218 unique citations identified, 12 studies met
      criteria for inclusion. Studies were geographically diverse, with six conducted
      in sub-Saharan Africa, three in South or Southeast Asia, and three in Latin
      America and the Caribbean. Target populations included adult women (N = 6),
      female sex workers/bar workers (N = 3), and youth/orphans (N = 3). All studies
      targeted females except two among youth/orphans. Study rigor was moderate, with
      two group-randomized trials and two individual-randomized trials. All
      interventions except three included some form of microfinance. Only a minority of
      studies found significant intervention effects on condom use, number of sexual
      partners, or other HIV-related behavioral outcomes; most studies showed no
      significant change, although some may have had inadequate statistical power. One
      trial showed a 55% reduction in intimate partner violence (adjusted risk ratio
      0.45, 95% confidence interval 0.23-0.91). No studies measured
      incidence/prevalence of HIV or sexually transmitted infections among intervention
      recipients. The evidence that income generation interventions influence HIV
      related behaviors and outcomes is inconclusive. However, these interventions may
      have important effects on outcomes beyond HIV prevention. Further studies
      examining not only HIV-related outcomes but also causal pathways and intermediate
      variables, are needed. Additional studies among men are also needed.

PMID- 24107190
TI  - Identifying women at risk for delayed presentation of breast cancer: a cross
      sectional study in Estonia.
AB  - BACKGROUND: Survival from breast cancer remains lower in Estonia than in most
      other European countries. More advanced stage and larger tumors that have impact
      on survival may be a result of delay in seeking help for breast cancer symptoms.
      The aim of this study was to identify determinants of delayed presentation among
      breast cancer patients in Estonia. METHODS: The study population included women
      with primary breast cancer diagnosed in Estonia in 2008-2010. All data were
      collected using structured personal interviews carried out by trained nurses in
      the hospital setting. Only patients with self-discovered symptoms were included
      in this analysis. Patient delay was measured as time elapsing from symptom self
      discovery to first medical consultation. The effect of different factors on the
      likelihood of prolonged delay (>90 days) was evaluated using logistic regression.
      RESULTS: Among 703 eligible patients, median patient delay was 16 days
      (interquartile range 5-54 days). Seventeen percent of the patients had their
      first medical consultation more than three months after self-detection of
      symptoms. In multivariate analysis, the risk of prolonged delay was significantly
      associated with age 65 years and over (OR 2.27, 95% CI 1.23-4.20), current
      smoking (OR 2.09, 95% CI 1.21-3.61), symptoms other than painless breast lump or
      breast pain (OR 1.84, 95% CI 1.08-3.16), no history of mammograms (OR 1.83, 95%
      CI 1.13-2.95), having received no information on breast cancer during past year
      (OR 1.77, 95% CI 1.05-2.99), and previous benign breast problems (OR 1.65, 95% CI
      1.01-2.67). Non-significant risk increase was seen with lower education.
      CONCLUSIONS: This study provides evidence that factors associated with delayed
      presentation of breast cancer in Eastern Europe are similar to those observed in
      Western countries. The results suggest that educational messages to general
      population should aim at increasing awareness of "non-lump" symptoms of breast
      cancer and encouraging women of all ages to present in a timely manner. Women at
      risk for delayed presentation such as smokers and women with no history of
      mammograms could be identified in the primary care setting.

PMID- 24107191
TI  - Re-examining the size/charge paradigm: differing in vivo characteristics of size-
      and charge-matched mesoporous silica nanoparticles.
AB  - The combination of nanoparticle (NP) size, charge, and surface chemistry (e.g.,
      extent of modification with polyethylene glycol (PEG)) is accepted as a key
      determinant of NP/cellular interactions. However, the influence of spatial
      arrangement and accessibility of the charged molecules on the NP surface vis-a
      vis the average surface charge (zeta (zeta) potential) is incompletely
      understood. Here we demonstrate that two types of mesoporous silica nanoparticles
      (MSNP) that are matched in terms of primary and hydrodynamic particle size,
      shape, pore structure, colloidal stability, and zeta potential, but differ in
      surface chemistry, viz. the spatial arrangement and relative exposure of surface
      amines, have profoundly different interactions with cells and tissues when
      evaluated in vitro and in vivo. While both particles are ~50 nm in diameter,
      PEGylated, and positively charged (zeta = +40 mV), PEG-PEI (MSNPs modified with
      exposed polyamines), but not PEG-NMe3(+) (MSNP modified with distributed,
      obstructed amines) rapidly bind serum proteins, diverse cells types in vitro, and
      endothelial and white blood cells in vivo (ex ovo chick embryo model). This
      finding helps elucidate the relative role of surface exposure of charged
      molecules vs zeta potential in otherwise physicochemically matched MSNP and
      highlights protein corona neutrality as an important design consideration when
      synthesizing cationic NPs for biological applications. 

PMID- 24107192
TI  - The making of I-BET762, a BET bromodomain inhibitor now in clinical development.
AB  - Bromodomain and extra-terminal (BET) proteins belong to a class of proteins
      collectively called epigenetic "readers". BET bromodomains have emerged as
      promising drug targets for treatment of cancers, inflammatory diseases, and other
      medical conditions. GlaxoSmithKline scientists have successfully optimized a
      class of benzodiazepines as inhibitors of BET bromodomains, without any prior
      knowledge of identified molecular targets. It thus is possible to hit a target
      without aiming at it. The optimized lead compound I-BET762 is currently being
      evaluated in a phase I clinical trial for treatment of human cancer. 

PMID- 24107193
TI  - Downscaling pollen-transport networks to the level of individuals.
AB  - Most plant-pollinator network studies are conducted at species level, whereas
      little is known about network patterns at the individual level. In fact, nodes in
      traditional species-based interaction networks are aggregates of individuals
      establishing the actual links observed in nature. Thus, emergent properties of
      interaction networks might be the result of mechanisms acting at the individual
      level. Pollen loads carried by insect flower visitors from two mountain
      communities were studied to construct pollen-transport networks. For the first
      time, these community-wide pollen-transport networks were downscaled from species
      species (sp-sp) to individuals-species (i-sp) in order to explore specialization,
      network patterns and niche variation at both interacting levels. We used a null
      model approach to account for network size differences inherent to the
      downscaling process. Specifically, our objectives were (i) to investigate whether
      network structure changes with downscaling, (ii) to evaluate the incidence and
      magnitude of individual specialization in pollen use and (iii) to identify
      potential ecological factors influencing the observed degree of individual
      specialization. Network downscaling revealed a high specialization of pollinator
      individuals, which was masked and unexplored in sp-sp networks. The average
      number of interactions per node, connectance, interaction diversity and degree of
      nestedness decreased in i-sp networks, because generalized pollinator species
      were composed of specialized and idiosyncratic conspecific individuals. An
      analysis with 21 pollinator species representative of two communities showed that
      mean individual pollen resource niche was only c. 46% of the total species niche.
      The degree of individual specialization was associated with inter- and
      intraspecific overlap in pollen use, and it was higher for abundant than for rare
      species. Such niche heterogeneity depends on individual differences in foraging
      behaviour and likely has implications for community dynamics and species
      stability. Our findings highlight the importance of taking interindividual
      variation into account when studying higher-order structures such as interaction
      networks. We argue that exploring individual-based networks will improve our
      understanding of species-based networks and will enhance the link between network
      analysis, foraging theory and evolutionary biology. 

PMID- 24107194
TI  - B. anthracis associated cardiovascular dysfunction and shock: the potential
      contribution of both non-toxin and toxin components.
AB  - The development of cardiovascular dysfunction and shock in patients with invasive
      Bacillus anthracis infection has a particularly poor prognosis. Growing evidence
      indicates that several bacterial components likely play important pathogenic
      roles in this injury. As with other pathogenic Gram-positive bacteria, the B.
      anthracis cell wall and its peptidoglycan constituent produce a robust
      inflammatory response with its attendant tissue injury, disseminated
      intravascular coagulation and shock. However, B. anthracis also produces lethal
      and edema toxins that both contribute to shock. Growing evidence suggests that
      lethal toxin, a metalloprotease, can interfere with endothelial barrier function
      as well as produce myocardial dysfunction. Edema toxin has potent adenyl cyclase
      activity and may alter endothelial function, as well as produce direct arterial
      and venous relaxation. Furthermore, both toxins can weaken host defense and
      promote infection. Finally, B. anthracis produces non-toxin metalloproteases
      which new studies show can contribute to tissue injury, coagulopathy and shock.
      In the future, an understanding of the individual pathogenic effects of these
      different components and their interactions will be important for improving the
      management of B. anthracis infection and shock. 

PMID- 24107195
TI  - Two neglected biologic risk factors in bone grafting and implantology: high low
      density lipoprotein cholesterol and low serum vitamin D.
AB  - Following a failure of a bone graft or an implant placement, the hypothesis of a
      biological abnormality is rarely considered as a possible cause. A systematic
      search of peer-reviewed literature for dyslipidemia or vitamin D deficiency may
      explain this lack of consideration. Excess low-density lipoprotein cholesterol
      (dyslipidemia) is responsible for a slower bone metabolism or lower dental
      implant osseointegration. In addition, vitamin D is a key factor for linking
      innate and adaptive immunity. Both of these factors are compromised under the
      conditions of vitamin D deficiency. Therefore, vitamin D deficiency slows implant
      osseointegration and increases the risk of graft infection. Vitamin D is also
      involved in immune function and therefore allergic reactions. 

PMID- 24107197
TI  - Validation of microscopic observation drug susceptibility testing for rapid,
      direct rifampicin and isoniazid drug susceptibility testing in patients receiving
      tuberculosis treatment.
AB  - Drug susceptibility testing (DST) is often needed in patients clinically failing
      tuberculosis (TB) therapy. Most studies of phenotypic direct drug susceptibility
      tests, such as microscopic observation drug susceptibility (MODS) tests, have
      been performed in patients not receiving TB treatment. The effect of ongoing TB
      treatment on the performance of MODS direct DST has not been previously explored,
      but patients failing such therapy constitute an important target group. The aim
      of this study was to determine the performance of MODS direct rifampicin and
      isoniazid DST in patients clinically failing first-line TB treatment, and to
      compare MODS direct DST with indirect proportion method DST. Sputa from 264 TB
      patients were cultured in parallel in Lowenstein-Jensen (LJ) and MODS assays;
      strains were tested for rifampicin and isoniazid susceptibility by the proportion
      method at the national reference laboratory. Ninety-three samples were culture
      positive by LJ and MODS (concordance of 96%; kappa 0.92). With conventional MODS
      plate DST reading (performed on the same day as the sample is classified as
      culture-positive), the isoniazid DST concordance was 96.8% (kappa 0.89), and the
      concordance for rifampicin susceptibility testing was 92.6% (kappa 0.80). Reading
      of MODS DST plates 1 week after cultures had been determined to be culture
      positive improved overall performance marginally-the isoniazid DST concordance
      was 95.7% (kappa 0.85); and the rifampicin DST concordance was 96.8% (kappa
      0.91). Sensitivity for detection of multidrug-resistant TB was 95.8%. MODS
      testing provided reliable rifampicin and isoniazid DST results for samples
      obtained from patients receiving TB therapy. A modified DST reading schedule for
      such samples, with a final reading 1 week after a MODS culture turns positive,
      marginally improves the concordance with reference DST.

PMID- 24107199
TI  - Effects of the transcendental meditation technique on trait anxiety: a meta
      analysis of randomized controlled trials.
AB  - OBJECTIVE: This meta-analysis of randomized controlled trials (RCTs) on the
      Transcendental Meditation(r) (TM) technique updates previous meta-analyses and
      assesses the effects of initial anxiety level, age, duration of practice,
      regularity of practice, research quality, author affiliation, and type of control
      group on effect sizes. DESIGN: This systematic review of the literature used the
      Comprehensive Meta-Analysis (CMA) program for core analyses of effect sizes, bias
      analysis, meta-regression, and moderator variable analysis. Comprehensive
      literature searches included databases devoted to meditation research. RESULTS:
      More than 600 TM research papers were identified; 14 of these addressed trait
      anxiety and reported on 16 studies among 1295 participants with diverse
      demographic characteristics. No adverse effects were reported. The standardized
      difference in mean, d, for the TM technique compared with controls receiving an
      active alternative treatment (10 studies) was d=-0.50 (95% CI, -.70 to -0.30;
      p=0.0000005). Compared with controls receiving treatment as usual (wait list or
      attention controls, 16 studies), d=-0.62 (95% CI, -0.82 to -0.43; p=1.37E-10).
      Meta-regression found that initial anxiety level, but not other variables,
      predicted the magnitude of reduction in anxiety (p=0.00001). Populations with
      elevated initial anxiety levels in the 80th to 100th percentile range (e.g.,
      patients with chronic anxiety, veterans with post-traumatic stress disorder,
      prison inmates) showed larger effects sizes (-0.74 to -1.2), with anxiety levels
      reduced to the 53rd to 62nd percentile range. Studies using repeated measures
      showed substantial reductions in the first 2 weeks and sustained effects at 3
      years. CONCLUSION: Overall, TM practice is more effective than treatment as usual
      and most alternative treatments, with greatest effects observed in individuals
      with high anxiety. More research is needed in this area, especially with high
      anxiety patients, conducted under medically supervised conditions.

PMID- 24107198
TI  - Sensory nerve conduction and somatosensory evoked potentials of the trigeminal
      nerve in horses with idiopathic headshaking.
AB  - BACKGROUND: Idiopathic headshaking (HSK) in horses is a distressing disorder in
      which the etiology and pathophysiology are unknown. HYPOTHESIS: Differences in
      sensory function of the trigeminal nerve exist between healthy and affected
      horses. ANIMALS: Six healthy mature geldings and 6 mature geldings with
      idiopathic HSK. METHODS: Prospective study. Sensory nerve action and
      somatosensory evoked potentials studies were performed. The stimulus site
      comprised the gingival mucosa dorsal to the maxillary canine. A pair of recording
      electrodes was placed along the sensory pathway of the trigeminal complex at the
      infraorbital nerve (R1), maxillary nerve (R2), spinal tract of trigeminal (R3),
      and somatosensory cortex (R4). Sensory nerve action potential latency (ms),
      amplitude (MUV), duration (ms), area under the curve (MUVms), and conduction
      velocity (m/s) were calculated. RESULTS: Threshold for activation of the
      infraorbital branch of the trigeminal nerve was significantly different between 5
      affected (<= 5 mA) and 6 control horses (>= 10 mA). After initiation of an action
      potential, there were no differences in all parameters measured and no
      differences between left and right sides. A horse with seasonal HSK tested during
      a time of no clinical manifestations showed a threshold for activation similar to
      control horses. CONCLUSIONS AND CLINICAL IMPORTANCE: This study confirms
      involvement of the trigeminal nerve hyperexcitability in the pathophysiology of
      disease. Further, results might support a functional rather than a structural
      alteration in the sensory pathway of the trigeminal complex that can be seasonal.
      The horse could serve as a natural animal model for humans with idiopathic
      trigeminal neuralgia.

PMID- 24107200
TI  - Limited spillover to humans from West Nile Virus viremic birds in Atlanta,
      Georgia.
AB  - West Nile Virus (WNV) is a mosquito-borne pathogen that impacts the health of its
      passerine bird hosts as well as incidentally infected humans in the United
      States. Intensive enzootic activity among the hosts and vectors does not always
      lead to human outbreaks, as is the situation throughout much of the southeastern
      United States. In Georgia, substantial yearly evidence of WNV in the mosquito
      vectors and avian hosts since 2001 has only led to 324 human cases. Although
      virus has been consistently isolated from mosquitoes trapped in Atlanta, GA,
      little is known about viral activity among the passerine hosts. A possible reason
      for the suppression of WNV spillover to humans is that viremic birds are absent
      from high human-use areas of the city. To test this hypothesis, multiseason,
      multihabitat, longitudinal WNV surveillance for active WNV viremia was conducted
      within the avian host community of urban Atlanta by collection of blood samples
      from wild passerine birds in five urban microhabitats. WNV was isolated from the
      serum of six blood samples collected from 630 (0.95%) wild passerine birds in
      Atlanta during 2010-2012, a proportion similar to that found in the Chicago, IL,
      area in 2005, when over 200 human cases were reported. Most of the viremic birds
      were Northern Cardinals, suggesting they may be of particular importance to the
      WNV transmission cycle in Georgia. Results indicated active WNV transmission in
      all microhabitats of urban Atlanta, except in the old-growth forest patches. The
      number of viremic birds was highest in Zoo Atlanta, where 3.5% of samples were
      viremic. Although not significant, these observations may suggest a possible
      transmission reduction effect of urban old-growth forests and a potential role in
      WNV amplification for Zoo Atlanta. Overall, spillover to humans remains a rare
      occurrence in urban Atlanta settings despite active WNV transmission in the avian
      population.

PMID- 24107201
TI  - Empiric antibiotic treatment of erythema migrans-like skin lesions as a function
      of geography: a clinical and cost effectiveness modeling study.
AB  - The skin lesion of early Lyme disease, erythema migrans (EM), is so
      characteristic that routine practice is to treat all such patients with
      antibiotics. Because other skin lesions may resemble EM, it is not known whether
      presumptive treatment of EM is appropriate in regions where Lyme disease is rare.
      We constructed a decision model to compare the cost and clinical effectiveness of
      three strategies for the management of EM: Treat All, Observe, and Serology as a
      function of the probability that an EM-like lesion is Lyme disease. Treat All was
      found to be the preferred strategy in regions that are endemic for Lyme disease.
      Where Lyme disease is rare, Observe is the preferred strategy, as presumptive
      treatment would be expected to produce excessive harm and increased costs. Where
      Lyme disease is rare, clinicians and public health officials should consider
      observing patients with EM-like lesions who lack travel to Lyme disease-endemic
      areas.

PMID- 24107202
TI  - Exposure to Echinococcus multilocularis, Toxocara canis, and Toxocara cati in
      Austria: a nationwide cross-sectional seroprevalence study.
AB  - Despite emerging risks for the spread of zoonotic diseases, data on human
      exposure to Echinococcus multilocularis and Toxocara spp., the causative
      parasites of the two most important helminthozoonoses in Central Europe, are
      limited. To investigate risk factors and exposure, we conducted a nationwide,
      cross-sectional serological study in 1046 healthy individuals, of which 425 were
      soldiers and 621 were civilians. Serum samples and information on possible risk
      factors for exposure, including previous foreign military assignments,
      residential area, animal contact, and regular outdoor activities, were obtained.
      Immunoglobulin G antibodies against Echinococcus multilocularis and Toxocara spp.
      were examined with an enzyme-linked immunosorbent assay (ELISA). Samples reactive
      in the ELISA for antibodies against Echinococcus multilocularis were considered
      positive only after confirmation by western blot. Overall, 66 (6.3%) individuals
      tested positive in the serologic screening for Toxocara spp. Occupational animal
      contact was the only risk factor significantly associated with a higher risk for
      being seropositive. None of the individuals were positive for antibodies against
      Echinococcus multilocularis. In conclusion, the present study demonstrates that
      exposure to Toxocara spp. is widespread in Austria and occupational animal
      contact is a risk factor for seropositivity.

PMID- 24107203
TI  - Quantitative PCR for detection of Babesia microti in Ixodes scapularis ticks and
      in human blood.
AB  - Babesia microti, the primary cause of human babesiosis in the United States, is
      transmitted by Ixodes scapularis ticks; transmission may also occur through blood
      transfusion and transplacentally. Most infected people experience a viral-like
      illness that resolves without complication, but those who are immunocompromised
      may develop a serious and prolonged illness that is sometimes fatal. The
      geographic expansion and increasing incidence of human babesiosis in the
      northeastern and midwestern United States highlight the need for high-throughput
      sensitive and specific assays to detect parasites in both ticks and humans with
      the goals of improving epidemiological surveillance, diagnosis of acute
      infections, and screening of the blood supply. Accordingly, we developed a B.
      microti-specific quantitative PCR (qPCR) assay (named BabMq18) designed to detect
      B. microti DNA in tick and human blood samples using a primer and probe
      combination that targets the 18S rRNA gene of B. microti. This qPCR assay was
      compared with two nonquantitative B. microti PCR assays by testing tick samples
      and was found to exhibit higher sensitivity for detection of B. microti DNA. The
      BabMq18 assay has a detection threshold of 10 copies per reaction and does not
      amplify DNA in I. scapularis ticks infected with Babesia odocoilei, Borrelia
      burgdorferi, Borrelia miyamotoi, or Anaplasma phagocytophilum. This highly
      sensitive and specific qPCR assay can be used for detection of B. microti DNA in
      both tick and human samples. Finally, we report the prevalence of B. microti
      infection in field-collected I. scapularis nymphs from three locations in
      southern New England that present disparate incidences of human babesiosis.

PMID- 24107204
TI  - Molecular phylogenetic analysis of Orientia tsutsugamushi based on the groES and
      groEL genes.
AB  - DNA sequences encoding the GroES and GroEL proteins of Orientia tsutsugamushi
      were amplified by the PCR and sequenced. Pairwise alignment of full-length groES
      and groEL gene sequences indicated high sequence similarity (90.4-100% and 90.3
      100%) in O. tsutsugamushi, suggesting that these genes are good candidates for
      the molecular diagnosis and phylogenetic analysis of scrub typhus. Comparisons of
      the 56-kD type-specific antigen (TSA) protein gene and the groES and groEL genes
      showed that genotypes based on the 56-kD TSA gene were not related to a cluster
      containing the groES and groEL genes in a dendrogram, suggesting that a gene
      rearrangement may be associated with homologous recombination in mites.

PMID- 24107205
TI  - Identification of diverse Salmonella serotypes, virulotypes, and antimicrobial
      resistance phenotypes in waterfowl from Chile.
AB  - Salmonella enterica is a pathogen with a wide host-range that presents great
      concern in developed and developing countries. To determine and characterize
      Salmonella strains found in Chile's waterfowl, we sampled 758 birds along 2000 km
      of the Chilean coast. In this sample, 46 isolates from 10 serotypes were
      detected, several with multidrug resistance phenotypes and different combinations
      of virulence-associated genes (virulotypes). These results suggest that
      Salmonella infection in waterfowl in Chile could have impacts on public and
      animal health.

PMID- 24107206
TI  - Molecular detection of Rickettsia africae, Rickettsia aeschlimannii, and
      Rickettsia sibirica mongolitimonae in camels and Hyalomma spp. ticks from Israel.
AB  - In this study, we aimed to identify and genetically characterize spotted fever
      group (SFG) rickettsiae in ticks, domestic one-humped camels, and horses from
      farms and Bedouin communities in southern Israel. A total of 618 ixodid ticks
      (Hyalomma dromedarii, Hyalomma turanicum, Hyalomma excavatum, and Hyalomma
      impeltatum) collected from camels and horses, as well as 152 blood samples from
      148 camels and four horses were included in the study. Initial screening for
      rickettsiae was carried out by targeting the gltA gene. Positive samples were
      further analyzed for rickettsial ompA, 17kDa, ompB, and 16S rRNA genes.
      Rickettsia aeschlimannii DNA was detected in the blood of three camels and 14
      ticks (H. dromedarii, H. turanicum, and H. excavatum). Rickettsia africae was
      found in six ticks (H. turanicum, H. impeltatum, H. dromedarii, and H.
      excavatum). In addition, Rickettsia sibirica mongolitimonae was detected in one
      H. turanicum tick. These findings represent the first autochthonous detection of
      R. africae in Israel. Previous detections of R. africae in Asia were reported
      from the Sinai Peninsula (Egypt) and Istanbul, only. Furthermore, we report for
      the first time the finding of R. aeschlimannii in H. turanicum and H. excavatum
      ticks, as well as the first identification of R. sibirica mongolitimonae in H.
      turanicum ticks. The tick species identified to harbor R. africae and other SFG
      rickettsiae have been reported to occasionally feed on people, and, therefore,
      physicians should be aware of the possible exposure of local communities and
      travelers, especially those in contact with camels, to these tick-borne
      rickettsial pathogens.

PMID- 24107207
TI  - Seroprevalence of Coxiella burnetii in Washington State domestic goat herds.
AB  - A caprine herd seroprevalence of Coxiella burnetii infection was determined by
      passive surveillance of domestic goat herds in Washington State. Serum samples
      (n=1794) from 105 herds in 31 counties were analyzed for C. burnetii antibodies
      using a commercially available Q fever antibody enzyme-linked immunosorbent assay
      (ELISA) test kit. The sera were submitted to the Washington Animal Disease
      Diagnostic Laboratory for routine serologic screening over an approximate 1-year
      period from November, 2010, through November, 2011. To avoid bias introduced by
      testing samples from ill animals, only accessions for routine screening of
      nonclinical animals were included in the study. A standard cluster sampling
      approach to investigate seroprevalence at the herd level was used to determine
      optimal study sample size. The results identified C. burnetii antibodies in 8.0%
      of samples tested (144/1794), 8.6% of goat herds tested (9/105), and 25.8% of
      counties tested (8/31). Within-herd seroprevalence in positive counties ranged
      from 2.9% to 75.8%. Counties with seropositive goats were represented in the
      western, eastern, southeastern, and Columbia basin agricultural districts of the
      state. To our knowledge this is the first county-specific, statewide study of C.
      burnetii seroprevalence in Washington State goat herds. The findings provide
      baseline information for future epidemiologic, herd management and public health
      investigations of Q fever.

PMID- 24107208
TI  - No serologic evidence for emerging Schmallenberg virus infection in dogs (Canis
      domesticus).
AB  - Schmallenberg virus, a novel orthobunyavirus, is spreading among ruminants,
      especially sheep and cattle, throughout Europe. To determine the risk for
      domestic dog infection, we conducted a survey among cases referred to the
      university Companion Animal Clinic to assess possible seroconversion. No evidence
      of transmission to dogs was detected.

PMID- 24107209
TI  - Bradycardia seen in children with Crimean-Congo hemorrhagic fever.
AB  - INTRODUCTION: Crimean-Congo hemorrhagic fever (CCHF) is a zoonotic viral disease
      with a high mortality rate. In clinical practice, we observed bradycardia in some
      pediatric patients with CCHF during the clinical course. So we aimed to report
      CCHF cases that presented bradycardia during the clinical course and the relation
      of bradycardia with the clinical findings and ribavirin therapy. METHODS: Charts
      of all hospitalized pediatric CCHF patients were reviewed with respect to age,
      sex, history of tick bite or history of removing a tick, other risk factors for
      CCHF transmission, and interval between the tick bite and the onset of symptoms.
      Outcomes and clinical and laboratory findings and medications were recorded for
      each patient. We searched the patient records for information regarding the
      existence of bradycardia. Bradycardia was accepted as the heart rate 2 standard
      deviations (SD) lower than the suspected heart rate based on age. RESULTS: Fifty
      two patients (mean age 11.2 +/- 4.4 years, 31 female) were enrolled into the
      study. Bradycardia was seen in seven patients. Six patients with bradycardia were
      male and only one was female, and the mean age was 13.1 +/- 1.6 years. It was
      observed that male gender is frequent among patients with bradycardia, as
      compared with those without bradycardia (p=0.01). Bleeding was found to be more
      frequent in patients with bradycardia (p=0.02). There were significant
      differences between the bradycardia and nonbradycardia groups with regard to the
      requirements for fresh frozen plasma transfusion, the number of platelet
      suspension given, requirement for intravenous immune globulin (IVIG) and in the
      days of stay in hospital (p=0.01, p=0.03, p=0.03, p=0.04, respectively).
      CONCLUSION: Reversible bradycardia might be seen in the clinical course of
      pediatric CCHF patients, and the clinicians must be aware of this finding. The
      possibility that ribavirin may potentiate bradycardia cannot be assessed without
      a placebo-control study. So further studies may help to reveal the cause of the
      bradycardia, the disease itself, or the ribavirin therapy. Hence this study
      supports the need for a randomized, placebo-controlled study to assess
      intravenous ribavirin in treating CCHF and to support approval of the drug.

PMID- 24107210
TI  - West Nile seroprevalence study in Bolivian horses, 2011.
AB  - West Nile virus (WNV) is a mosquito-borne virus belonging to the family
      Flaviviridae included in the Japanese encephalitis antigenic complex (JEAC). A
      seroepidemiological study was carried out in 2011 using 160 horse sera collected
      from different areas of Bolivia to investigate the presence of WNV antibody. A
      high proportion (59.4%) of the tested sera were positive to a commercially
      available WNV competitive enzyme-linked immunosorbent assay (C-ELISA). Sixty-six
      randomly selected C-ELISA-positive sera were further tested by WNV plaque
      reduction neutralization test (PRNT), virus neutralization (VN), and
      immunoglobulin M (IgM)-WNV ELISA to exclude false-positive results due to
      possible cross-reactions to other members of the JEAC and to investigate if the
      horses were recently infected. No WNV IgM was detected in these samples, whereas
      neutralizing antibodies were found in 21 and 18 samples by PRNT and VN,
      respectively. In conclusion, a high proportion of the Bolivian horses included in
      this study reacted serologically against viruses of the JEAC. WNV was partially
      responsible (31.8%) for these reactions, supporting the conclusion that WNV
      circulated in Bolivia.

PMID- 24107211
TI  - Detection of Ehrlichia canis and Anaplasma platys DNA using multiplex PCR.
AB  - We hereby propose a novel sensitive, specific, and cost-efficient method to
      detect Ehrlichia canis and Anaplasma platys DNA from canine whole blood samples
      by multiplex PCR. Blood samples from hemoparasited dogs attending the Veterinary
      Hospital at the Universidade Federal Rural da Amazonia-UFRA, Belem, Brazil, were
      collected in tubes containing EDTA. Amplification of E. canis and A. platys 16S
      rDNA by nested (n) PCR was successfully achieved by using primers specific to the
      Anaplasmataceae in the first round of PCR, followed by a second round of PCR
      using E. canis-specific primers in conjunction with A. platys-specific primers.
      The amplicons obtained were cloned and sequenced, yielding sequences of 478 and
      473 bp (including primers) pertaining to regions of the 16S rDNA of E. canis and
      A. platys, respectively. The protocol we here propose may help to measure the
      prevalence of canine monocytic ehrlichiosis (CME) and canine cyclic
      thrompocytopenia, not only in northern Brazil, where there is no data available,
      but also elsewhere.

PMID- 24107212
TI  - Seroprevalence of zoonotic parasites in pigs slaughtered in the Kathmandu Valley
      of Nepal.
AB  - For several years, the demand for pork has been on the rise in Nepal. To assess
      the importance of pork as a carrier of zoonotic agents, we performed a cross
      sectional study in the Kathmandu Valley of Nepal, in which we serologically
      determined the infection status of slaughtered pigs with regard to three of the
      most important parasites transmitted through pork consumption: Trichinella spp.,
      Taenia solium cysticerci, and Toxoplasma gondii. From 2007 to 2010, 742 pigs were
      sampled at slaughter, of which 0.1% (95% confidence interval [CI] 0.0-0.7%) were
      found positive for Trichinella infection, 13.8% (95% credibility interval [CrI]
      0.8-28.5%) for T. solium cysticercosis, and 11.7% (95% CI 5.2-17.5%) for
      Toxoplasma infection. Further monitoring of the related animal and human disease
      burden and strengthening of food safety protocols throughout the pork production
      chain are strongly recommended.

PMID- 24107213
TI  - Molecular identification of vertebrate and hemoparasite DNA within mosquito blood
      meals from eastern North Dakota.
AB  - To understand local transmission of vector-borne diseases, it is important to
      identify potential vectors, characterize their host feeding patterns, and
      determine if vector-borne pathogens are circulating within the region. This study
      simultaneously investigated these aspects of disease transmission by collecting
      engorged mosquitoes within two rural study sites in the central Red River Valley
      of North Dakota. Mosquitoes were identified, midguts were excised, and the blood
      was expelled from the midguts. DNA was extracted from blood meals and subjected
      to PCR and direct sequencing to identify the vertebrate origin of the blood.
      Using different primer sets, PCR was used to screen for two types of vector-borne
      pathogens, filarioid nematodes and hemosporidian parasites. White-tailed deer
      were the primary source of blood meals for the eight aedine mosquito species
      collected. None of the 288 deer-derived blood meals contained filarioid or
      hemosporidian DNA. In contrast, 18 of 32 Culex tarsalis and three of three Cx.
      pipiens blood meals contained avian blood, representing eight different species
      of birds. Of 24 avian-derived blood meals examined, 12 contained Plasmodium DNA,
      three of which also contained Leucocytozoon DNA (i.e., dual infection). Potential
      confounding effects resulting from parasite acquisition and development from
      previous blood meals (e.g., oocysts) were eliminated because host blood had been
      removed from the midguts prior to DNA extraction. Thus, specific parasite
      lineages/species could be unequivocally linked to specific vertebrate species. By
      combining mosquito identification with molecular techniques for identifying blood
      meal source and pathogens, a relatively small sample of engorged mosquitoes
      yielded important new information about mosquito feeding patterns and
      hemosporidia infections in birds. Thorough analyses of wild-caught engorged
      mosquitoes and other arthropods represent a powerful tool in understanding the
      local transmission of vector-borne and zoonotic diseases.

PMID- 24107214
TI  - High risk of tick bites in Dutch gardens.
AB  - Lyme borreliosis is the most prevalent tick-borne disease throughout the Northern
      Hemisphere. Because the disease has large socioeconomic consequences, there is an
      urgent need to further educate the public to stimulate preventive behavior.
      Unfortunately, risk factors for tick bites are poorly known. In this study, we
      determined the habitats and activities at risk for tick bites for people of
      different age categories using reports of Dutch citizens. Most people, 43%, were
      bitten in the forest, and an unexpected large number of people reported tick
      bites from their gardens (31%). Hiking, hobby gardening, and playing were the
      most-mentioned activities during which tick bites were received; people aged from
      50 to 69 and children below 10 were bitten most. Different age categories were
      bitten in different habitats and during different activities. People aged from 0
      to 60 reported most tick bites related to visiting a forest and hiking, whereas
      people older than 60 were mainly bitten in gardens. The percentage of garden and
      hobby gardening tick bites increased with age, but was also high for children
      less than 10 years of age. We suggest that these findings should be taken into
      account for the development of prevention strategies aiming to decrease the
      number of Lyme borreliosis cases.

PMID- 24107215
TI  - Evaluation of Crimean-Congo hemorrhagic fever virus infection in children.
AB  - Crimean-Congo haemorrhagic fever (CCHF) is a fatal viral infection and an
      important public health issue in Turkey because of its high case fatality rate.
      Severity criteria of CCHF were defined previously in adults on the basis of
      epidemiological, clinical, and laboratory findings,. This study evaluated the
      course of CCHF in children. Between January, 2009, and November, 2012, 41
      patients aged between 1 and 17 years (mean 9.78 +/- 4.85) with a diagnosis of
      CCHF were included in the study. According to results of our study, Turkish
      pediatric patients had a milder course of CCHF.

PMID- 24107216
TI  - Postexposure prophylaxis of tick-borne relapsing fever: lessons learned from
      recent outbreaks in Israel.
AB  - Tick-borne relapsing fever (TBRF) is endemic in Israel. Military activities pose
      a particular risk for TBRF, and its prevention is based on heightened awareness
      and risk stratification by active surveillance of tick bites and selective
      postexposure prophylaxis (PEP) with doxycycline for tick-bitten individuals. We
      report three outbreaks of TBRF affecting 35 exposed military personnel, with an
      average recognized tick bite rate of approximately 50% and an attack rate of 25
      50%. Of 10 TBRF cases, 20% had no evidence of tick bites and thus restriction of
      PEP administration to individuals with recognized tick bites contributed to TBRF
      occurrence. As a result of a revised policy, 24 soldiers (including eight with
      recognized and 16 with unrecognized tick bites) received antimicrobials following
      the diagnosis of TBRF among their cohorts, and none of these individuals
      subsequently developed TBRF. The probability for TBRF among exposed individuals
      associated with well-established cases of TBRF warrants that prompt doxycycline
      administration be considered in all individuals who share risk factors,
      regardless of tick bite status.

PMID- 24107217
TI  - Bartonellae in domestic and stray cats from Israel: comparison of bacterial
      cultures and high-resolution melt real-time PCR as diagnostic methods.
AB  - To determine the occurrence of feline bartonellosis in Israel, blood samples were
      collected from 179 stray and 155 domestic cats from 18 cities or villages in
      central and northcentral Israel. Samples were screened for Bartonella infection
      by culture isolation and molecular detection using high-resolution melt (HRM)
      real-time PCR assay targeting the 16S-23S rRNA internal transcribed spacer (ITS).
      All positive samples were confirmed by two additional HRM real-time PCR assays
      targeting two fragments of the beta-subunit of RNA polymerase (rpoB) and the 16S
      rRNA genes. The prevalence of Bartonella spp. infection in the general tested
      population was 25.1% (84/334). A higher prevalence was detected in the stray
      (30.7%; 55/179) than the domestic cats (18.7%; 29/155). Bartonella henselae,
      Bartonella clarridgeiae, and Bartonella koehlerae were highly prevalent in both
      cat populations, however their distribution among the two populations varied
      significantly (p=0.016). B. clarridgeiae and B. koehlerae were found to be more
      prevalent in stray than domestic cats, whereas B. henselae was evenly
      distributed. Co-infection with two or more different Bartonella spp. was
      determined in 2.1% (7) of the cats. The ITS HRM real-time PCR assay used in this
      study was shown to have a greater screening power than bacterial isolation,
      detecting 94.0% (79/84) compared to 35.7% (30/84), respectively, of all positive
      samples. The high prevalence of these zoonotic Bartonella species, coupled with
      the overpopulation of stray cats, and increased numbers of domestic cats in the
      major urban centers in Israel represent a significant threat for the public
      health in this country.

PMID- 24107218
TI  - Chronic rhinosinusitis in asthma is a negative predictor of quality of life:
      results from the Swedish GA(2)LEN survey.
AB  - BACKGROUND: Asthma and chronic rhinosinusitis (CRS) both impair quality of life,
      but the quality-of-life impact of comorbid asthma and CRS is poorly known. The
      aim of this study was to evaluate the impact of CRS and other relevant factors on
      quality of life in asthmatic subjects. METHODS: This Swedish cohort (age 17-76
      years) consists of 605 well-characterized asthmatics with and without CRS, 110
      individuals with CRS only, and 226 controls and is part of the Global Allergy and
      Asthma European Network (GA(2) LEN) survey. The Mini Asthma Quality of Life
      Questionnaire (mAQLQ), the Euro Quality of Life (EQ-5D) health questionnaire,
      spirometry, skin prick test (SPT), exhaled nitric oxide (FeNO), smell test, and
      peak nasal inspiratory flow were used. RESULTS: Subjects having both asthma and
      CRS have lower mAQLQ scores in all domains (P < 0.001) and a lower EQ-5D index
      value and EQ-5D VAS value (P < 0.001) compared to those with asthma only.
      Asthmatics with CRS have significantly lower FEV1%pred and FVC%pred (88.4 [85.1
      91.7] and 99.9 [96.7-103.0], respectively) compared with asthma only (91.9 [90.3
      93.4] and 104.0 [102.5-105.5], respectively P < 0.05). Multiple regression
      analysis shows that low asthma quality of life is associated with having CRS (P <
      0.0001), lower lung function (P = 0.008), current smoking (P = 0.01), BMI > 30
      kg/m2 (P = 0.04), high age (P = 0.03), and a negative SPT (P = 0.04).
      CONCLUSIONS: Comorbid CRS was a significant and independent negative predictor of
      quality of life in asthmatics. Other negative factors were lower lung function,
      current smoking, obesity, advanced age, and having nonatopic asthma.

PMID- 24107219
TI  - Controllable self-assembly of sodium caseinate with a zwitterionic vitamin
      derived bolaamphiphile.
AB  - The control of self-assembly of sodium caseinate (SC) including the formation of
      mixed layers, microspheres, or nanoparticles is highly relevant to the
      microstructure of food and the design of promising drug delivery systems. In this
      paper, we designed a structure-switchable zwitterionic bolaamphiphile, 1,12
      diaminododecanediorotate (DDO), from orotic acid, which has special binding sites
      and can guide the self-assembly of SC. Complexation between SC and DDO was
      investigated using dynamic light scattering, transmission electron microscopy,
      differential scanning calorimetry, and fluorescence spectra measurements.
      Monomeric DDO was bound to the negatively charged sites on the SC micelle and
      made the structure of SC more compact with decreased electrostatic repulsion
      between the head groups. Vesicular DDO led to reassociation of vesicles with
      enlarged size via preferable hydrophobic interactions. Moreover, the aggregation
      between SC and DDO was found to be temperature-dependent and reversible. This
      research provides an effective way to control the reversible self-assembly of SC
      by the zwitterionic vitamin-derived bolaamphiphile. 

PMID- 24107220
TI  - Single-tooth replacement in the anterior maxilla by means of immediate
      implantation and early loading: clinical and aesthetic results at 5 years.
AB  - BACKGROUND: The hypothesis of the present study was that the early loading of
      single implants-supported restorations, replacing single extracting teeth in the
      anterior region of the maxilla in case of fresh extraction sockets with residual
      hard and soft tissue preservation, could be a successful procedure. METHODS:
      Twenty-one implants were placed into maxillary anterior fresh extraction sockets
      using a flapless technique. Temporary restorations, which were fabricated from
      the impression taken immediately after implant placement, were connected within 2
      weeks. These temporary restorations were adjusted in order to avoid any direct
      occlusive contacts. Six months after implantation, the implants were restored
      with single-teeth all-ceramic prostheses. Patients were followed for 5 years.
      Radiographic and clinical examinations were made at baseline, at time of
      definitive crowns delivery, and each subsequent year. Survival rate, cortical
      bone responses, and peri-implant mucosal responses were evaluated. RESULTS: One
      implant was lost at 6 months. Clinical osseointegration of 20 implants was
      achieved (95.2% implant survival rate after 5 years) with minimal gingival
      recession and papillae preservation. The mean change in marginal cortical bone
      level was 0.40 mm at 6 months and 0.83 mm at 5 years. CONCLUSIONS: Within the
      limit of the present study, the data indicate that, under a strictly controlled
      oral hygienic regimen, single-tooth implants, with immediate placement and early
      loading protocol, may be used in anterior maxillary fresh extraction sockets with
      residual hard and soft tissues preservation, if patients are selected carefully
      and if high primary stability is strictly followed.

PMID- 24107222
TI  - Highly sensitive surface-enhanced Raman scattering sensing of heparin based on
      antiaggregation of functionalized silver nanoparticles.
AB  - We report a simple and sensitive surface-enhanced Raman scattering (SERS)
      platform for the detection of heparin, based on antiaggregation of 4
      mercaptopyridine (4-MPY) functionalized silver nanoparticles (Ag NPs). Here,
      protamine was employed as a medium for inducing the aggregation of negatively
      charged 4-MPY functionalized Ag NPs through surface electrostatic interaction,
      which resulted in significantly enhanced Raman signal of the Raman reporter.
      However, in the presence of heparin, the interaction between heparin and
      protamine decreased the concentration of free protamine, which dissipated the
      aggregated 4-MPY functionalized Ag NPs and thus decreased Raman enhancement
      effect. The degree of aggregation and Raman enhancement effect was proportional
      to the concentration of added heparin. Under optimized assay conditions, good
      linear relationship was obtained over the range of 0.5-150 ng/mL (R(2) = 0.998)
      with a minimum detectable concentration of 0.5 ng/mL in standard aqueous
      solution. Furthermore, the developed method was also successfully applied for
      detecting heparin in fetal bovine serum samples with a linear range of 1-400
      ng/mL. 

PMID- 24107221
TI  - Volatility of organic aerosol: evaporation of ammonium sulfate/succinic acid
      aqueous solution droplets.
AB  - Condensation and evaporation modify the properties and effects of atmospheric
      aerosol particles. We studied the evaporation of aqueous succinic acid and
      succinic acid/ammonium sulfate droplets to obtain insights on the effect of
      ammonium sulfate on the gas/particle partitioning of atmospheric organic acids.
      Droplet evaporation in a laminar flow tube was measured in a Tandem Differential
      Mobility Analyzer setup. A wide range of droplet compositions was investigated,
      and for some of the experiments the composition was tracked using an Aerosol Mass
      Spectrometer. The measured evaporation was compared to model predictions where
      the ammonium sulfate was assumed not to directly affect succinic acid
      evaporation. The model captured the evaporation rates for droplets with large
      organic content but overestimated the droplet size change when the molar
      concentration of succinic acid was similar to or lower than that of ammonium
      sulfate, suggesting that ammonium sulfate enhances the partitioning of
      dicarboxylic acids to aqueous particles more than currently expected from simple
      mixture thermodynamics. If extrapolated to the real atmosphere, these results
      imply enhanced partitioning of secondary organic compounds to particulate phase
      in environments dominated by inorganic aerosol. 

PMID- 24107223
TI  - An online database for plant image analysis software tools.
AB  - BACKGROUND: Recent years have seen an increase in methods for plant phenotyping
      using image analyses. These methods require new software solutions for data
      extraction and treatment. These solutions are instrumental in supporting various
      research pipelines, ranging from the localisation of cellular compounds to the
      quantification of tree canopies. However, due to the variety of existing tools
      and the lack of central repository, it is challenging for researchers to identify
      the software that is best suited for their research. RESULTS: We present an
      online, manually curated, database referencing more than 90 plant image analysis
      software solutions. The website, plant-image-analysis.org, presents each software
      in a uniform and concise manner enabling users to identify the available
      solutions for their experimental needs. The website also enables user feedback,
      evaluations and new software submissions. CONCLUSIONS: The plant-image
      analysis.org database provides an overview of existing plant image analysis
      software. The aim of such a toolbox is to help users to find solutions, and to
      provide developers a way to exchange and communicate about their work.

PMID- 24107224
TI  - Cytochrome-P450-cytochrome-b5 interaction in a membrane environment changes 15N
      chemical shift anisotropy tensors.
AB  - It has been well realized that the dependence of chemical shift anisotropy (CSA)
      tensors on the amino acid sequence, secondary structure, dynamics, and
      electrostatic interactions can be utilized in the structural and dynamic studies
      of proteins by NMR spectroscopy. In addition, CSA tensors could also be utilized
      to measure the structural interactions between proteins in a protein-protein
      complex. To this end, we report the experimentally measured backbone amide-(15)N
      CSA tensors for a membrane-bound 16.7 kDa full-length rabbit cytochrome-b5
      (cytb5), in complexation with a 55.8 kDa microsomal rabbit cytochrome P450 2B4
      (cytP4502B4). The (15)N-CSAs, determined using the (15)N CSA/(15)N-(1)H dipolar
      coupling transverse cross-correlated rates, for free cytb5 are compared with
      those for the cytb5 bound to cytP4502B4. An overall increase in backbone amide
      (15)N transverse cross-correlated rates for the cytb5 residues in the cytb5
      cytP450 complex is observed as compared to the free cytb5 residues. Due to fast
      spin-spin relaxation (T2) and subsequent broadening of the signals in the
      complex, we could measure amide-(15)N CSAs only for 48 residues of cytb5 as
      compared to 84 residues of free cytb5. We observed a change in (15)N CSA for most
      residues of cytb5 in the complex, as compared to free cytb5, suggesting a dynamic
      interaction between the oppositely charged surfaces of anionic cytb5 and cationic
      cytP450. The mean values of (15)N CSA determined for residues in helical, sheet,
      and turn regions of cytb5 in the complex are -184.5, -146.8, and -146.2 ppm,
      respectively, with an overall average value of -165.5 ppm (excluding the values
      from residues in more flexible termini). The measured CSA value for residues in
      helical conformation is slightly larger as compared to previously reported
      values. This may be attributed to the paramagnetic effect from Fe(III) of the
      heme in cytb5, which is similar to our previously reported values for the free
      cytb5. 

PMID- 24107226
TI  - Urocortin 2 is associated with abdominal aortic aneurysm and mediates anti
      proliferative effects on vascular smooth muscle cells via corticotrophin
      releasing factor receptor 2.
AB  - AAA (abdominal aortic aneurysm) is an important cause of sudden death in older
      adults, but there is no current effective drug therapy for this disease. The UCNs
      (urocortins1-3) and their receptors: CRFR (corticotrophin-releasing factor
      receptor)-1 and -2 have been implicated in various CVDs (cardiovascular
      diseases). We assessed the relative expression of UCN1-3 in AAA by qRT-PCR
      (quantitative reverse transcription-PCR) and ELISA, and examined in vitro how
      UCN2 affects human aortic VSMC (vascular smooth muscle cell) Akt phosphorylation,
      pro-inflammatory cytokine IL (interleukin)-6 secretion, proliferation, cell cycle
      and apoptosis. UCN2 and CRFR2 expression were significantly up-regulated in
      biopsies from the AAA body. AAA body biopsies released high amounts of UCN2 in
      vitro. Median plasma UCN2 concentrations were 2.20 ng/ml (interquartile range
      1.14-4.55 ng/ml, n=67) in AAA patients and 1.11 ng/ml (interquartile range 0.76
      2.55 ng/ml, n=67) in patients with non-aneurysmal PAD (peripheral artery disease)
      (P=0.001). Patients with UCN2 in the highest quartile had a 4.12-fold (95%
      confidence interval, 1.37-12.40) greater prevalence of AAA independent of other
      risk factors, P=0.012. In vitro, UCN2 significantly inhibited VSMC Akt
      phosphorylation and proliferation in a dose-dependent manner. UCN2 induced VSMC
      G1 cell-cycle arrest and increased IL-6 secretion over 24 h. The CRFR2 antagonist
      astressin-2B significantly abrogated the effects of UCN2 on VSMCs. In conclusion,
      UCN2 is significantly associated with AAA and inhibits VSMC proliferation by
      inducing a G1 cell cycle arrest suggesting a plausible regulatory role in AAA
      pathogenesis. 

PMID- 24107225
TI  - Daily milk intake improves vitamin B-12 status in young vegetarian Indians: an
      intervention trial.
AB  - BACKGROUND: Asymptomatic Indian lacto vegetarians, who make up more than half of
      the Indian population in different geographic regions, have distinctly low
      vitamin B-12 concentrations than non- vegetarians. Vegetarians consume milk but
      it seems that the amount is not enough to improve vitamin B-12 status or vitamin
      B-12 concentration in milk itself may be low. The aim of this study was to
      determine if daily milk consumption can improve vitamin B-12 status. METHODS:
      Fifteen male and 36 female, young healthy post-graduate volunteers participated.
      Blood from ten participants (4 males and 6 females) was collected (day-1). They
      continued their regular diet for next fourteen days and on day-15, blood of all
      51 participants was collected, plasma vitamin B-12 concentration was measured and
      were divided into two groups; Normal (vitamin B-12 >148 pmol/L, n = 22) and
      Vitamin B-12 deficient (<148 pmol/L, n = 29), the remaining plasma was stored.
      All participants consumed 600 ml. of non-enriched buffalo milk (200 * 3) during
      the day along with their usual diet. Next day blood was collected for plasma
      holotranscobalamin II measurement. Subjects from deficient group continued to
      drink 400 ml of milk daily for next 14 days and blood was collected on day-30.
      Plasma holotranscoabalamin II (day-1, 15, 16, 30), vitamin B-12, folate, total
      homocysteine, creatinine and hematoloical parameters (day-1, 15, 30), and milk
      vitamin B-12 concentrations (day-15, 16, 30) were measured. RESULTS: Fifty seven
      per cent of the participants were vitamin B-12 deficient and 65% were
      hyperhomocysteinemic. No significant difference in biomarkers was observed when
      there was no intervention. Plasma holotranscobalamin II concentration increased
      from 19.6 to 22.27 pmol/L (p < 0.0001) 24 hrs after milk load in the whole group.
      Plasma vitamin B-12 increased from 92.5 to 122 pmol/L and tHcy concentrations
      decreased from 31.9 to 24.9 MU mol/L (p < 0.0001 for both) 14 days after regular
      milk intake in vitamin B-12 deficient subjects. CONCLUSIONS: Regular intake of
      milk improved vitamin B-12 status of vitamin B-12 deficient vegetarians
      indicating a potential dietary strategy to improve the vitamin status.

PMID- 24107227
TI  - Life review in groups? An explorative analysis of social processes that
      facilitate or hinder the effectiveness of life review.
AB  - OBJECTIVES: Life review can be implemented within a group as well as on an
      individual level. There have been few discussions about which the format is most
      effective. This study investigates the social aspects of a life-review group
      intervention from the perspective of the client within the context of a large,
      randomized controlled trial. METHOD: This was an exploratory study using a
      qualitative methodology. We conducted semi-structured interviews to explore how
      participants felt about the benefits and barriers of receiving life review in a
      group. Transcripts of the interviews were analyzed using inductive analysis.
      RESULTS: The social processes of life review in a group included experiencing a
      sense of belonging, feeling accepted, finding good company, disclosing oneself,
      learning to express oneself, finding recognition, realizing that others have
      problems too, being more successful at coping than others, learning from others,
      and being able to help others. Negative processes were less often mentioned and
      included having difficulties with sharing in a group, finding no recognition, and
      anxiety caused by the prospect of finding no recognition. These social processes
      can be divided into three categories: first, having a good atmosphere in the
      group; second, disclosure to peers; and third, relating to others. CONCLUSION:
      Our results reveal a variety of social processes that may facilitate the effects
      of life-review therapy. Future research, however, is needed to further examine
      the importance of these social processes and their effects on depression.

PMID- 24107228
TI  - Mutational and genetic determinants of lambda6 light chain amyloidogenesis.
AB  - Approximately 25% of the lambda6 light chains have glycine rather than arginine
      at position 25, which is an allelic variant of the IGLV6-57 (6a) locus. The Gly25
      variant has been shown to decrease the folding stability of the germline lambda6
      V(L) protein 6aJL2 by 1.7 kcal.mol(-1). In this work, we compared the
      thermodynamic and fibrillogenic properties of the amyloidosis (AL) derived
      recombinant (r) V(L) protein AR, which contains the allelic variant Gly25, with
      those of germline rV(L) 6aJL2-R25G and the lambda6 disease-associated V(L)
      proteins Wil (AL) and Jto (myeloma). Our experiments show that of the four
      proteins AR is the least stable; forms amyloid fibrils at physiological
      temperature, pH and ionic strength; has the shortest lag time; and elongates
      homologous seeds most efficiently. We conclude that the Gly25 allelic variant,
      together with the somatic mutations, contributes importantly to the extremely low
      stability and high amyloidogenicity of the AL-derived protein AR.

PMID- 24107229
TI  - Pyrrolizidine alkaloids from Onosma erecta.
AB  - The MeOH extract of the aerial parts of Onosma erecta afforded four new
      pyrrolizidine alkaloids, 7-O-acetylechinatine N-oxide (1), a viridinatine N-oxide
      stereoisomer (2), 7-epi-echimiplatine N-oxide (3), and onosmerectine N-oxide (4),
      and two additional new natural products, the acid 2,3-dimethyl-2,3,4
      trihydroxypentanoic acid (5) and the acyloin 4-methyl-2-hydroxypentanone (6). 

PMID- 24107230
TI  - Dental implant status of patients receiving long-term nursing care in Japan.
AB  - BACKGROUND: The increase in implant patients is expected to give rise to a new
      problem: the changing general health status of those who have had implants
      placed. PURPOSE: The aim of this present study was to find out the needs of and
      proper measures for elderly implant patients in long-term care facilities.
      MATERIALS AND METHODS: A questionnaire was sent by mail to 1,591 long-term care
      health facilities, daycare services for people with dementia, and private nursing
      homes for the elderly in the Osaka area, which is in the middle area of Japan, in
      order to extract patients with cerebrovascular disease or dementia who were
      possibly at risk of inadequate oral self-care, as well as patients with implants.
      RESULTS: Approximately half of all facilities responded that they cannot
      recognize implants, and many facilities did not know anything about oral care for
      implant patients. Residents with implants were reported at 19% of all facilities.
      Also, the facilities pointed out problems with implants relating to the
      difference in oral care between implants and natural teeth. CONCLUSIONS: There
      are people with implants in some 20% of caregiving facilities, and there is a low
      level of understanding regarding implants and their care among nurses and care
      providers who are providing daily oral care.

PMID- 24107231
TI  - Photoinduced solid state conversion of a radical sigma-dimer to a pi-radical
      pair.
AB  - Irradiation in the solid state of the hypervalent 4c-6e S...S-S...S bridged sigma
      dimer of a bisdithiazolyl radical leads to its photodissociation into a pair of
      pi-radicals. The transformation has been monitored by optical spectroscopy,
      single crystal X-ray diffraction, and magnetic susceptibility measurements. As a
      result of the large electronic reorganization involved in the dimer-to-radical
      interconversion, the photogenerated S = 1/2 radical state is remarkably thermally
      stable, persisting to 242 K before reverting to the S = 0 dimer. 

PMID- 24107232
TI  - Trophic niche width increases with bill-size variation in a generalist passerine:
      a test of niche variation hypothesis.
AB  - The niche variation hypothesis (NVH) predicts that populations with wider niches
      are phenotypically more variable than populations with narrower niches, which is
      frequently used to explain diversifying processes such as ecological release.
      However, not all empirical evidence supports the NVH. Furthermore, a relationship
      between population phenotypic variation and niche width can be caused by sexual
      selection or environmental gradients, which should be carefully considered along
      with competition in explaining niche variation. In this study, we used eight
      populations of a generalist passerine species, Paradoxornis webbianus (vinous
      throated parrotbill), to test the NVH. We assessed evidence of ecological sexual
      dimorphism and environmental gradients in bill morphology of P. webbianus. A
      total of 170 P. webbianus from eight sites ranging 24-2668 m in altitude were
      included in this study. We used two principal components to quantify bill
      morphology: one describes bill size and the other describes bill slenderness. We
      used stable carbon and nitrogen isotope values of bird feathers to quantify
      trophic positions, and we estimated population trophic niche width using Bayesian
      standardized ellipse area. Paradoxornis webbianus with larger and more slender
      bills fed at higher trophic levels and population trophic niche width tended to
      increase with bill-size variation, supporting the NVH. The males had larger bills
      and marginally higher nitrogen isotope values than the females, suggesting
      ecological sexual dimorphism. Despite a positive correlation between bill size
      and wing length indicating sexual selection for larger male size, only three of
      the eight populations showed both male-biased bill size and male-biased wing
      length. Sexual dimorphism explained 13%-64% of bill-size variation across sites,
      suggesting its role in niche variation could vary greatly among populations. The
      variation in bill slenderness in P. webbianus increased with elevation. However,
      neither bill-size variation nor trophic niche width changed with elevation.
      Therefore, environmental gradients that could be reflected in the elevation are
      not likely to drive the observed morphological and niche variation. This study
      provides an empirical case for the NVH and highlights the importance of
      investigating sexual dimorphism and environmental gradients in studies of niche
      dynamics.

PMID- 24107233
TI  - Eating patterns and mental health problems in early adolescence--a cross
      sectional study of 12-13-year-old Norwegian schoolchildren.
AB  - OBJECTIVE: To investigate the association between eating patterns and mental
      health problems in young Norwegian adolescents (12-13 years of age). DESIGN:
      Cross-sectional study. Dietary information was reported by parents using a
      retrospective FFQ. Eating patterns were identified using principal component
      analysis. The Strengths and Difficulties Questionnaire was used to measure mental
      health problems. The association between eating patterns and mental health
      problems was examined using multiple logistic regression analysis. SETTING:
      Primary schools, Telemark County, Norway. SUBJECTS: Children (n 1095) aged 12-13
      years and their parents. RESULTS: Children with high scores on a 'varied
      Norwegian' eating pattern were less likely to have indications of any psychiatric
      disorders (adjusted OR = 0.5; 95 % CI 0.3, 1.0) and hyperactivity-inattention
      disorders (adjusted OR = 0.4; 95 % CI 0.2, 0.8) than children with low scores on
      this pattern. Children with high scores on a 'junk/convenient' eating pattern
      were more likely to have indications of hyperactivity-inattention disorders
      (adjusted OR = 3.4; 95 % CI 1.3, 8.6) than children with low scores on this
      pattern. Children with high scores on a 'snacking' eating pattern were more
      likely to have indications of conduct/oppositional disorders (adjusted OR = 3.8;
      95 % CI 1.2, 11.5) than those with low scores on this eating pattern.
      CONCLUSIONS: We identified a significant association between eating patterns and
      mental health problems in young adolescents, independently of physical activity,
      sedentary activity and background variables. A diverse diet rich in unrefined
      plant foods, fish and regular meals was associated with better mental health,
      while energy-dense, nutrient-poor diets and irregular meals were associated with
      poorer mental health.

PMID- 24107234
TI  - Piper sarmentosum: a new hope for the treatment of osteoporosis.
AB  - Osteoporosis is a major global health problem. Osteoporosis is characterized by
      the loss of bone mass and strength which leads to an increased risk of fracture.
      Glucocorticoid treatment is the leading cause of secondary osteoporosis.
      Glucocorticoid action in bone depends upon the expression of 11beta
      hydroxysteroid dehydrogenase type 1 enzyme (11beta-HSD1). The oestrogen deficient
      state causes osteoporosis due to enhancement of osteoclastogenesis by oxidative
      stress which leads to increased bone resorption. Piper sarmentosum (Daun Kaduk)
      is commonly used in the local cuisine of South East Asia. It is also
      traditionally used to treat many diseases such as inflammation, dermatitis and
      joint pain. Studies have revealed antioxidant properties through its flavonoids
      compound naringenin which acts as a superoxide scavenger that may help in the
      endogenous antioxidant defence system to protect bone against osteoporosis.
      Recent studies found that Ps extract has the ability to inhibit the expression
      and activity of 11beta-HSD1 in adipose tissue and bone which restored bone
      structure and strength. It also accelerates fracture healing in the oestrogen
      deficient state through its antioxidant properties. The cost of conventional
      treatment is high and together with the adverse effects it leads to
      noncompliance. Treatment modalities with herbal medicine, less side effects and
      is cheaper need to be explored.This review focused on the therapeutic effect of
      Ps extract on fracture healing in ovariectomized rats and its protective effects
      against glucocorticoid induced osteoporotic rats. 

PMID- 24107235
TI  - Immunological and clinical consequences of splenectomy in a multiple sclerosis
      patient treated with natalizumab.
AB  - OBJECTIVE: Here we report a case of a splenectomized white woman with natalizumab
      associated progressive multifocal leukoencephalopathy (PML), occurring as early
      as after 11 infusions and provide blood fluorescence-activated cell sorting
      (FACS) analyses before and after natalizumab treatment. DESIGN: This is a report
      of a single case with immunological studies. METHODS: Methods comprised
      neurologic examination, magnetic resonance imaging, and cerebrospinal fluid (CSF)
      studies as well as immune cell FACS analyses from blood. RESULTS: Diagnosis of
      PML was established after positive John Cunningham virus (JCV) DNA was detected
      in the CSF. An immune reconstitution inflammatory syndrome was treated with
      repeated cycles of steroid pulses and intravenous immunoglobulins. Reduced
      numbers of memory B cells, which might play an important role in antiviral immune
      response, were detected in the blood. Moreover the percentage of CD19+ B cells
      was elevated in our post-splenectomy patient as compared to a control cohort of
      multiple sclerosis (MS) patients under natalizumab therapy. CONCLUSION:
      Splenectomy may increase the risk for the development of natalizumab-associated
      PML via effects on the B cell compartment. It may be regarded as a risk factor in
      MS patients independent from the duration of disease.

PMID- 24107236
TI  - Can head and neck cancer patients be discharged after three years?
AB  - BACKGROUND: Follow-up surveillance of head and neck cancer patients varies
      throughout the UK. The heterogeneity of these patients limits the applicability
      of a standardised protocol. Improvements in our understanding of the natural
      history of the disease may assist in the tailoring of resources to patients.
      METHOD: Prospective data collected at the Cumberland Infirmary over a 13-year
      period were analysed, primarily focusing upon recurrence rates and time to
      recurrence. RESULTS: In keeping with other studies, recurrence of head and neck
      squamous cell carcinoma was found to be maximal within the first three years of
      treatment, regardless of subsite. CONCLUSION: Hospital-based surveillance may be
      safely discontinued after three years for some patients. Laryngeal carcinoma may
      require further surveillance due to possible delayed recurrence of a second
      primary formation. Emphasis must be placed on patient education, accessibility to
      head and neck services, and the existence of a robust system to facilitate urgent
      referrals.

PMID- 24107237
TI  - Spatial distribution of nitrogen fixation in methane seep sediment and the role
      of the ANME archaea.
AB  - Nitrogen (N2) fixation was investigated at Mound 12, Costa Rica, to determine its
      spatial distribution and biogeochemical controls in deep-sea methane seep
      sediment. Using (15)N2 tracer experiments and isotope ratio mass spectrometry
      analysis, we observed that seep N2 fixation is methane-dependent, and that N2
      fixation rates peak in a narrow sediment depth horizon corresponding to increased
      abundance of aggregates of anaerobic methanotrophic archaea (ANME-2) and sulfate
      reducing bacteria (SRB). Using fluorescence in situ hybridization coupled to
      nanoscale secondary ion mass spectrometry (FISH-NanoSIMS), we directly measured
      (15)N2 uptake by ANME-2/SRB aggregates (n = 26) and observed maximum (15)N
      incorporation within ANME-2-dominated areas of the aggregates, consistent with
      previous analyses. NanoSIMS analysis of single cells (n = 34) from the same
      microcosm experiment revealed no (15)N2 uptake. Together, these observations
      suggest that ANME-2, and possibly physically associated SRB, mediate the majority
      of new nitrogen production within the seep ecosystem. ANME-2 diazotrophy was
      observed while in association with members of two distinct orders of SRB:
      Desulfobacteraceae and Desulfobulbaceae. The rate of N2 fixation per unit volume
      biomass was independent of the identity of the associated SRB, aggregate size and
      morphology. Our results show that the distribution of seep N2 fixation is
      heterogeneous, laterally and with depth in the sediment, and is likely influenced
      by chemical gradients affecting the abundance and activity of ANME-2/SRB
      aggregates.

PMID- 24107238
TI  - Stabilization of metal nanoparticle films on glass surfaces using ultrathin
      silica coating.
AB  - Metal nanoparticle (NP) films, prepared by adsorption of NPs from a colloidal
      solution onto a preconditioned solid substrate, usually form well-dispersed
      random NP monolayers on the surface. For certain metals (e.g., Au, Ag, Cu), the
      NP films display a characteristic localized surface plasmon resonance (LSPR)
      extinction band, conveniently measured using transmission or reflection
      ultraviolet-visible light (UV-vis) spectroscopy. The surface plasmon band
      wavelength, intensity, and shape are affected by (among other parameters) the NP
      spatial distribution on the surface and the effective refractive index (RI) of
      the surrounding medium. A major concern in the formation of such NP assemblies on
      surfaces is a commonly observed instability, i.e., a strong tendency of the NPs
      to undergo aggregation upon removal from the solution and drying, expressed as a
      drastic change in the LSPR band. Since various imaging modes and applications
      require dried NP films, preservation of the film initial (wet) morphology and
      optical properties upon drying are highly desirable. The latter is achieved in
      the present work by introducing a convenient and generally applicable method for
      preventing NP aggregation upon drying while preserving the original film
      morphology and optical response. Stabilization of Au and Ag NP monolayers toward
      drying is accomplished by coating the immobilized NPs with an ultrathin (3.0-3.5
      nm) silica layer, deposited using a sol-gel reaction performed on an intermediate
      self-assembled aminosilane layer. The thin silica coating prevents NP aggregation
      and maintains the initial NP film morphology and LSPR response during several
      cycles of drying and immersion in water. It is shown that the silica-coated NP
      films retain their properties as effective LSPR transducers. 

PMID- 24107239
TI  - Assembly of graphene oxide at water/oil interfaces: tessellated nanotiles.
AB  - The interfacial assembly of graphene oxide (GO) at the water/oil interface and
      its kinetics were systematically studied. GO nanosheets were found to segregate
      to the water/oil interface and interact with quaternized block copolymer chains
      by the peripheral carboxyl groups on the GO. If the interfacial area is
      decreased, then GO, assembled at and confined to the interface, jams and then
      buckles. An analysis of the kinetics of the assembly processes leads to the
      conclusion that the diffusion of GO to the interface is the rate-determining
      step. The morphology of the jammed GO film was investigated, and TEM images show
      that GO sheets form a mosaic or tile across the whole oil/water interface. 

PMID- 24107240
TI  - Presence of sandflies infected with Leishmania infantum and Massilia virus in the
      Marseille urban area.
AB  - Leishmaniasis is considered a rural disease in Europe. However, circumstantial
      evidence has indicated urban transmission of leishmaniasis and phleboviruses in
      the urban area of Marseille, France. To investigate this urban transmission,
      sandflies were trapped in 33 locations in the urban area (horse farms, public
      gardens and a residential area). Sandflies were always captured: 87.8% were
      Phlebotomus perniciosus, a vector of Leishmania infantum and Toscana and Massilia
      viruses. RT-PCR and cell culture inoculation identified the Massilia virus in
      2/99 pools of sandflies, and PCR identified Leishmania in 5/99. No dual infection
      was observed, but both pathogens were detected in samples from the same trapping
      site.

PMID- 24107242
TI  - All-atom molecular dynamics simulation of photosystem II embedded in thylakoid
      membrane.
AB  - The molecular dynamics simulation is reported. The latest data on photosystem II
      structure, a thylakoid membrane model with the same lipid class distribution and
      fatty acid composition as the native thylakoid membrane, are used. The results
      indicate that the transfer of water, oxygen and protons has different pathways.
      The root mean square (rms)-fluctuation analysis of trajectory revealed that the
      residues surrounding the oxygen-evolving center (OEC) show small fluctuations and
      that most of the water molecules there show large fluctuation and are on proposed
      pathways for water and oxygen transfer. The water molecules near the OEC having
      small fluctuation could be involved in proton transfer. We assume that each kind
      of pathway characterized in this study plays a role in photosynthesis. 

PMID- 24107243
TI  - Intervention for a multi-character processing deficit in a Greek-speaking child
      with surface dyslexia.
AB  - A case study with a 12-year-old boy, R.F., who was a monolingual speaker of Greek
      is reported. R.F. showed slow word reading and a difficulty in spelling irregular
      words but not nonwords. Assessments revealed that R.F. did not appear to have a
      phonological deficit, but indicated impaired multicharacter processing ability
      for visually presented letter arrays. On the basis of previous research linking
      multicharacter processing and reading we developed an intervention aimed at
      improving R.F.'s ability to report letter arrays of increasing length. Following
      a 9-week programme, improvement was observed, and investigation of R.F.'s reading
      revealed gains in single word reading speed and accuracy. The findings support
      the significance of intervention studies for testing hypotheses regarding causal
      relationships among cognitive processes and the notion of specific profiles of
      developmental dyslexia/dysgraphia in both opaque and transparent orthographies. 

PMID- 24107241
TI  - Travel patterns during pregnancy: comparison between Global Positioning System
      (GPS) tracking and questionnaire data.
AB  - BACKGROUND: Maternal exposures to traffic-related air pollution have been
      associated with adverse pregnancy outcomes. Exposures to traffic-related air
      pollutants are strongly influenced by time spent near traffic. However, little is
      known about women's travel activities during pregnancy and whether questionnaire
      based data can provide reliable information on travel patterns during pregnancy.
      OBJECTIVES: Examine women's in-vehicle travel behavior during pregnancy and
      examine the difference in travel data collected by questionnaire and global
      positioning system (GPS) and their potential for exposure error. METHODS: We
      measured work-related travel patterns in 56 pregnant women using a questionnaire
      and one-week GPS tracking three times during pregnancy (<20 weeks, 20-30 weeks,
      and >30 weeks of gestation). We compared self-reported activities with GPS
      derived trip distance and duration, and examined potentially influential factors
      that may contribute to differences. We also described in-vehicle travel behavior
      by pregnancy periods and influences of demographic and personal factors on daily
      travel times. Finally, we estimated personal exposure to particle-bound
      polycyclic aromatic hydrocarbon (PB-PAH) and examined the magnitude of exposure
      misclassification using self-reported vs. GPS travel data. RESULTS: Subjects
      overestimated both trip duration and trip distance compared to the GPS data. We
      observed moderately high correlations between self-reported and GPS-recorded
      travel distance (home to work trips: r = 0.88; work to home trips: r = 0.80).
      Better agreement was observed between the GPS and the self-reported travel time
      for home to work trips (r = 0.77) than work to home trips (r = 0.64). The
      subjects on average spent 69 and 93 minutes traveling in vehicles daily based on
      the GPS and self-reported data, respectively. Longer daily travel time was
      observed among participants in early pregnancy, and during certain pregnancy
      periods in women with higher education attainment, higher income, and no
      children. When comparing self-reported vs. GPS data, we found that estimated
      personal exposure to PB-PAH did not differ remarkably at the population level,
      but the difference was large at an individual level. CONCLUSION: Self-reported
      home-to-work data overestimated both trip duration and trip distance compared to
      GPS data. Significant differences in PAH exposure estimates were observed at
      individual level using self-reported vs. GPS data, which has important
      implications in air pollution epidemiological studies.

PMID- 24107244
TI  - Differential distribution of parvalbumin- and calbindin-D28K-immunoreactive
      neurons in the rat periaqueductal gray matter and their colocalization with
      enzymes producing nitric oxide.
AB  - The distribution, colocalization with enzymes producing nitric oxide (NO), and
      the synaptic organization of neurons containing two calcium-binding proteins
      (CaBPs) - parvalbumin (Parv) and calbindin-D28K (Calb) - were investigated in the
      rat periaqueductal gray matter (PAG). Parv-immunopositive (ParvIP) neurons were
      detected in the mesencephalic nucleus and rarely in the PAG. CalbIP neurons were
      found both in the dorsolateral (PAG-dl) and ventrolateral PAG (PAG-vl); their
      size ranged from 112.96 MUm(2) (PAG-dl) to 125.13 MUm(2) (PAG-vl).
      Ultrastructurally Parv and Calb immunoreactivity was mostly found in dendritic
      profiles. Axon terminals containing each of the two CaBPs formed symmetric
      synapses. Moreover both Parv and Calb were used to label a subpopulation of NO
      producing neurons. Colocalization was investigated using two protocols: (i) a
      combination of Calb and Parv immunocytochemistry (Icc) with nicotinamide adenine
      dinucleotide phosphate diaphorase (NADPH-d) histochemistry (Hi) and (ii) neuronal
      NO synthase-Icc (nNOS) (immunofluorescence). Both techniques demonstrated a
      complete lack of colocalization of Parv and NADPH-d/nNOS in PAG neurons. Double
      labeled (DL) neurons (Calb-NADPH-d; Calb-nNOS) were detected in PAG-dl. NADPH-d
      Hi/Calb-Icc indicated that 41-47% of NADPH-d-positive neurons contained Calb,
      whereas 17-23% of CalbIP cells contained NADPH-d. Two-color immunofluorescence
      revealed that 53-66% of nNOSIP cells colocalized with Calb and 24-34% of CalbIP
      neurons contained nNOS. DL neuron size was 104.44 MUm(2); neurons labeled only
      with NADPH-d or Calb measured 89.793 MUm(2) and 113.48 MUm(2), respectively.
      Together with previous findings (Barbaresi et al. [2012]) these data suggest
      that: Therefore the important aspect of the PAG intrinsic organization emerging
      from this and previous double-labeling studies is the chemical diversity of NO
      synthesizing neurons, which is likely related to the different functions in which
      these neurons are involved.

PMID- 24107247
TI  - Getting over qPCR's technical hurdles.

PMID- 24107246
TI  - Contribution of unmeasured anions to acid-base disorders and its association with
      altered demeanor in 264 calves with neonatal diarrhea.
AB  - BACKGROUND: The quantitative effect of strong electrolytes, unmeasured anions
      (UAs), pCO2 , and plasma protein concentrations in determining plasma pH and
      bicarbonate (HCO3 (-) ) can be demonstrated using the physicochemical approach.
      Demeanor of calves with diarrhea is associated with acidemia, dehydration, and
      hyper-d-lactatemia. HYPOTHESIS: Unmeasured anions are a major factor influencing
      changes in plasma pH and HCO3 (-) of calves with diarrhea and UAs and strong UAs,
      estimated by anion gap (AG) and strong ion gap (SIG), respectively, are more
      strongly associated with alteration of demeanor compared to other acid-base
      variables. ANIMALS: A total of 264 calves with diarrhea from two data sets (DS1
      and DS2). METHODS: Retrospective study. Forward stepwise regression was performed
      to determine the relationship between measured pH or HCO3 (-) , and
      physicochemical variables. A two-way ANOVA was performed to investigate the
      association between acid-base variables and attitude (bright, obtunded, and
      stuporous), posture (standing, sternal or lateral recumbency), and strength of
      suckling reflex (strong, weak, or absent). RESULTS: Increased strong UAs
      estimated by SIG was the most important contributor to changes in measured pH and
      HCO3 (-) (DS1: r(2) 66 and 59%, DS2: 39 and 42%, P < .0001). SIG and AG were
      correlated to deteriorating calf demeanor for all three clinical scoring
      categories: attitude, posture, and suckle reflex (P < .0001). CONCLUSION AND
      CLINICAL RELEVANCE: Elevated concentrations of strong UAs were the primary cause
      of acidemia and had an important influence on the demeanor of calves with
      diarrhea. These findings emphasize the importance of the calculation of UAs when
      evaluating acid-base abnormalities in calves.

PMID- 24107248
TI  - Special news feature--DNA sequencing. Targeting the tree of life.

PMID- 24107245
TI  - Paleoclimatic modeling and phylogeography of least killifish, Heterandria
      formosa: insights into Pleistocene expansion-contraction dynamics and
      evolutionary history of North American Coastal Plain freshwater biota.
AB  - BACKGROUND: Climatic and sea-level fluctuations throughout the last Pleistocene
      glacial cycle (~130-0 ka) profoundly influenced present-day distributions and
      genetic diversity of Northern Hemisphere biotas by forcing range contractions in
      many species during the glacial advance and allowing expansion following glacial
      retreat ('expansion-contraction' model). Evidence for such range dynamics and
      refugia in the unglaciated Gulf-Atlantic Coastal Plain stems largely from
      terrestrial species, and aquatic species Pleistocene responses remain relatively
      uninvestigated. Heterandria formosa, a wide-ranging regional endemic, presents an
      ideal system to test the expansion-contraction model within this biota. By
      integrating ecological niche modeling and phylogeography, we infer the
      Pleistocene history of this livebearing fish (Poeciliidae) and test for several
      predicted distributional and genetic effects of the last glaciation. RESULTS:
      Paleoclimatic models predicted range contraction to a single southwest Florida
      peninsula refugium during the Last Glacial Maximum, followed by northward
      expansion. We inferred spatial-population subdivision into four groups that
      reflect genetic barriers outside this refuge. Several other features of the
      genetic data were consistent with predictions derived from an expansion
      contraction model: limited intraspecific divergence (e.g. mean mtDNA p-distance =
      0.66%); a pattern of mtDNA diversity (mean Hd = 0.934; mean pi = 0.007)
      consistent with rapid, recent population expansion; a lack of mtDNA isolation-by
      distance; and clinal variation in allozyme diversity with higher diversity at
      lower latitudes near the predicted refugium. Statistical tests of mismatch
      distributions and coalescent simulations of the gene tree lent greater support to
      a scenario of post-glacial expansion and diversification from a single refugium
      than to any other model examined (e.g. multiple-refugia scenarios). CONCLUSIONS:
      Congruent results from diverse data indicate H. formosa fits the classic
      Pleistocene expansion-contraction model, even as the genetic data suggest
      additional ecological influences on population structure. While evidence for Plio
      Pleistocene Gulf Coast vicariance is well described for many freshwater species
      presently codistributed with H. formosa, this species demography and
      diversification departs notably from this pattern. Species-specific expansion
      contraction dynamics may therefore have figured more prominently in shaping
      Coastal Plain evolutionary history than previously thought. Our findings bolster
      growing appreciation for the complexity of phylogeographical structuring within
      North America's southern refugia, including responses of Coastal Plain freshwater
      biota to Pleistocene climatic fluctuations.

PMID- 24107250
TI  - Optimizing methodologies for PCR-based DNA methylation analysis.
AB  - Comprehensive analysis of DNA methylation patterns is critical for understanding
      the molecular basis of many human diseases. While hundreds of PCR-based DNA
      methylation studies are published every year, the selection and implementation of
      appropriate methods for these studies can be challenging for molecular genetics
      researchers not yet familiar with methylation analysis. Here we review the most
      commonly used PCR-based DNA methylation analysis techniques: bisulfite sequencing
      PCR (BSP), methylation specific PCR (MSP), MethyLight, and methylation-sensitive
      high resolution melting (MS-HRM). We provide critical analysis of the strengths
      and weaknesses of each approach as well as a series of guidelines to assist in
      selecting and implementing an appropriate method. 

PMID- 24107251
TI  - Combining RNAi and in vivo confocal microscopy analysis of the photoconvertible
      fluorescent protein Dendra2 to study a DNA repair protein.
AB  - Clinical approaches for tumor treatment often rely on combination therapy where a
      DNA damaging agent is used in combination with a DNA repair protein inhibitor.
      For this reason, great efforts have been made during the last decade to identify
      inhibitors of DNA repair proteins or, alternatively, small molecules that
      specifically alter protein stability or trafficking. Unfortunately, when studying
      these drug candidates, classical biochemical approaches are prone to artifacts.
      The apurinic/apyrimidinic endonuclease (APE1) protein is an essential component
      of the base excision repair (BER) pathway that is responsible for repairing DNA
      damage caused by oxidative and alkylating agents. In this work, we combined
      conditional gene expression knockdown of APE1 protein by RNA interference (RNAi)
      technology with re-expression of an ectopic recombinant form of APE1 fused with
      the photoconvertible fluorescent protein (PCFP) Dendra2. Dendra2 did not alter
      the subcellular localization or endonuclease activity of APE1. We calculated APE1
      half-life and compared these results with the classical biochemical approach,
      which is based on cycloheximide (CHX) treatment. In conclusion, we combined RNAi
      and in vivo confocal microscopy to study a DNA repair protein demonstrating the
      feasibility and the advantage of this approach for the study of the cellular
      dynamic of a DNA repair protein. 

PMID- 24107252
TI  - A rapid and efficient method to purify proteins at replication forks under native
      conditions.
AB  - Tools for studying replication fork dynamics are critical for dissecting the
      mechanisms of DNA replication, DNA repair, histone deposition, and epigenetic
      memory. Isolation of protein on nascent DNA (iPOND) is an elegant method for
      purifying replication fork proteins. Here, we present accelerated native iPOND
      (aniPOND), a simplification of the iPOND procedure with improved protein yield.
      Cell membrane lysis and nuclei harvesting are combined in one step to reduce
      washes and minimize sample loss. A mild nuclei lysis protocol is then used to
      better preserve DNA-protein complexes. aniPOND is faster than iPOND, avoids
      formaldehyde cross-linking, and improves protein yield 5- and 20-fold for the
      CAF1-complex or PCNA respectively. Moreover, using aniPOND, but not iPOND, we
      could detect the polycomb repressive complex 2 (PRC2) components SUZ12, EZH2, and
      RBBP4 at replication forks. This faster, higher-yield method will facilitate MS
      analysis of replication fork complexes.

PMID- 24107253
TI  - The choice of reference gene affects statistical efficiency in quantitative PCR
      data analysis.
AB  - Quantitative polymerase chain reaction (qPCR), a highly sensitive method of
      measuring gene expression, is widely used in biomedical research. To produce
      reliable results, it is essential to use stably expressed reference genes (RGs)
      for data normalization so that sample-to-sample variation can be controlled. In
      this study, we examine the effect of different RGs on statistical efficiency by
      analyzing a qPCR data set that contains 12 target genes and 3 RGs. Our results
      show that choosing the most stably expressed RG for data normalization does not
      guarantee reduced variance or improved statistical efficiency. We also provide a
      formula for determining when data normalization will improve statistical
      efficiency and hence increase the power of statistical tests in data analysis. 

PMID- 24107254
TI  - Questionnaire-based study to assess the association between management practices
      and mastitis within tie-stall and free-stall dairy housing systems in
      Switzerland.
AB  - BACKGROUND: Prophylactic measures are key components of dairy herd mastitis
      control programs, but some are only relevant in specific housing systems. To
      assess the association between management practices and mastitis incidence, data
      collected in 2011 by a survey among 979 randomly selected Swiss dairy farms, and
      information from the regular test day recordings from 680 of these farms was
      analyzed. RESULTS: The median incidence of farmer-reported clinical mastitis
      (ICM) was 11.6 (mean 14.7) cases per 100 cows per year. The median annual
      proportion of milk samples with a composite somatic cell count (PSCC) above
      200,000 cells/ml was 16.1 (mean 17.3) %. A multivariable negative binomial
      regression model was fitted for each of the mastitis indicators for farms with
      tie-stall and free-stall housing systems separately to study the effect of other
      (than housing system) management practices on the ICM and PSCC events (above
      200,000 cells/ml). The results differed substantially by housing system and
      outcome. In tie-stall systems, clinical mastitis incidence was mainly affected by
      region (mountainous production zone; incidence rate ratio (IRR) = 0.73), the
      dairy herd replacement system (1.27) and farmers age (0.81). The proportion of
      high SCC was mainly associated with dry cow udder controls (IRR = 0.67), clean
      bedding material at calving (IRR = 1.72), using total merit values to select
      bulls (IRR = 1.57) and body condition scoring (IRR = 0.74). In free-stall
      systems, the IRR for clinical mastitis was mainly associated with stall
      climate/temperature (IRR = 1.65), comfort mats as resting surface (IRR = 0.75)
      and when no feed analysis was carried out (IRR = 1.18). The proportion of high
      SSC was only associated with hand and arm cleaning after calving (IRR = 0.81) and
      beef producing value to select bulls (IRR = 0.66). CONCLUSIONS: There were
      substantial differences in identified risk factors in the four models. Some of
      the factors were in agreement with the reported literature while others were not.
      This highlights the multifactorial nature of the disease and the differences in
      the risks for both mastitis manifestations. Attempting to understand these
      multifactorial associations for mastitis within larger management groups
      continues to play an important role in mastitis control programs.

PMID- 24107255
TI  - A study examining the appropriateness of a self-rated alcohol-related clinical
      confidence tool as a method of measurement among registered hospital nurses using
      Rasch analysis.
AB  - AIMS: This paper is a report of a study, which seeks to determine if self
      reported estimates of RNs' self-rated confidence in responding to alcohol use in
      patients is a psychometrically sound measure. BACKGROUND: Alcohol-related harm is
      a global public health problem. Nurses are the largest group of health
      professionals worldwide, with evidence showing that despite being well placed to
      respond, they are not engaging in this important role. DESIGN: Instrument
      development. METHOD: The study was a survey set in a large teaching hospital in
      England, UK. The Clinical Confidence Questionnaire was made available to a
      convenience sample of 200 RNs in 2007, with a response rate of 22%. Rasch
      analysis was used to develop a scale for future learning based on the conjoint
      estimates of registered hospital nurses abilities to meet needs of patients
      requiring nursing care of different complexities related to alcohol use in
      patients. RESULTS: Outcomes verify that registered hospital nurses' self-rated
      clinical confidence measures for their own nursing abilities in responding to
      alcohol use in patients can be reliably estimated and a hierarchical scale of
      learning can be generated to inform curricula content and learning processes.
      CONCLUSION: Current health policy in the UK identifies nurses as having a role in
      responding to alcohol-related harm. More focus should, therefore, be placed on
      ensuring that they are prepared to fully engage with patients in assessing and
      responding to alcohol use through specific education, training and skill
      development. The self-rated clinical confidence tool offers evidence as an
      acceptable method of measurement in this area.

PMID- 24107256
TI  - Protein kinase C and its inhibitors in the regulation of inflammation: inducible
      nitric oxide synthase as an example.
AB  - Protein kinase C (PKC) is a family of ten isoenzymes that play a crucial role in
      cellular signal transduction. Studies with PKC knockout animals have revealed
      that many of the isoenzymes are involved in cell growth, proliferation and
      differentiation. Several PKC isoenzymes have also been shown to be important
      mediators in inflammation and immunity, particularly in lymphocyte responses.
      However, less is known about the role of PKC in the regulation of the expression
      of inflammatory genes. In inflammatory processes, nitric oxide is primarily
      produced by inducible nitric oxide synthase (iNOS) in inflammatory cells, such as
      macrophages. In innate immunity, nitric oxide functions as an effector molecule
      towards the infectious organisms. Increased levels of nitric oxide are also
      produced by inflammatory and tissue cells in inflammatory diseases, such as
      asthma and arthritis. In this MiniReview, the role of PKC isoenzymes in the
      pathogenesis and as a potential drug target in inflammation will be discussed
      presenting iNOS as an example of an inflammatory gene regulated by the
      pleiotropic PKC signalling pathway. 

PMID- 24107257
TI  - The topical administration of bisphosphonates in implant surgery: a randomized
      split-mouth prospective study with a follow-up up to 5 years.
AB  - OBJECTIVE: To evaluate the efficacy of the topical administration of
      bisphosphonates in implant therapy. MATERIALS AND METHODS: Thirty-nine
      consecutive patients were selected for a split-mouth study. Inclusion criteria
      were: presence of a bilateral or total edentulism, ability to tolerate
      conventional implant procedures, older than 18 years. Ten patients were smokers.
      Ten patients were fully edentulous in both maxilla and mandible, 12 patients had
      fully edentulous maxilla or mandible, and 17 were bilaterally partially
      edentulous (9 in the mandible and 8 in the maxilla). A one-stage procedure was
      adopted in all cases. The prosthetic phase started 10 weeks after implant
      insertion. Each patient received implants on the control side and the test side,
      with insertion performed in the conventional way on the control side; on the test
      side, a 3% clodronate solution mixed with a surfactant (Tween-20) at a 1:3 ratio
      was topically administered both at the implant surface and at the implant site.
      RESULTS: One hundred fifty-five implants were inserted. The test and control
      groups included 75 and 80 implants, respectively. The implant insertion torque
      was no less than 30 Ncm. A total of 7 implants failed in the control group (6
      before loading and one after 12 months of loading). No failure occurred on the
      test side. By the 5-year follow-up, no further implant failure had been recorded.
      Overall, implant survival rates at 5 years for the test and control groups were,
      respectively, 100% and 91.3%, the difference being significant (p < .01). Mean
      marginal bone loss was 0.85 +/- 0.71 mm in the test group and 1.12 +/- 0.85 mm in
      the control group after 1 year of loading and stable thereafter. The difference
      was not significant. CONCLUSIONS: The topical administration of bisphosphonates
      may positively affect implant survival in the preloading and postloading phases
      in partially and fully edentulous patients. However, a larger study population is
      needed to verify these promising clinical results.

PMID- 24107259
TI  - Survey finds support for payments to doctors from commercial companies to be made
      public.

PMID- 24107258
TI  - The heritability of clinically diagnosed attention deficit hyperactivity disorder
      across the lifespan.
AB  - BACKGROUND: No prior twin study has explored the heritability of clinically
      diagnosed attention deficit hyperactivity disorder (ADHD). Such studies are
      needed to resolve conflicting results regarding the importance of genetic effects
      for ADHD in adults. We aimed to estimate the relative contribution of genetic and
      environmental influences for clinically diagnosed ADHD across the lifespan with a
      specific focus on ADHD in adults. METHOD: Information on zygosity and sex was
      obtained from 59514 twins born between 1959 and 2001 included in the nationwide
      population-based Swedish Twin Registry. Clinical data for ADHD diagnoses (i.e.
      stimulant or non-stimulant medication for ADHD) were obtained from the Swedish
      Prescribed Drug Register (PDR) and from the National Patient Register (i.e. ICD
      10 diagnosis of ADHD). Twin methods were applied to clinical data of ADHD
      diagnoses using structural equation modeling with monozygotic (MZ) and dizygotic
      (DZ) twins. RESULTS: The best-fitting model revealed a high heritability of ADHD
      [0.88, 95% confidence interval (CI) 0.83-0.92] for the entire sample. However,
      shared environmental effects were non-significant and of minimal importance. The
      heritability of ADHD in adults was also substantial (0.72, 95% CI 0.56-0.84).
      CONCLUSIONS: This study shows that the heritability of clinically diagnosed ADHD
      is high across the lifespan. Our finding of high heritability for clinically
      diagnosed ADHD in adults indicates that the previous reports of low heritability
      are best explained by rater effects, and that gene-identification studies of ADHD
      in adults need to consider pervasiveness (e.g. multiple raters) and
      developmentally (e.g. childhood-onset criteria) informative data.

PMID- 24107260
TI  - Inhibition of IgE binding to cross-reactive carbohydrate determinants enhances
      diagnostic selectivity.
AB  - BACKGROUND: Allergy diagnosis by determination of allergen-specific IgE is
      complicated by clinically irrelevant IgE, of which the most prominent example is
      IgE against cross-reactive carbohydrate determinants (CCDs) that occur on
      allergens from plants and insects. Therefore, CCDs cause numerous false-positive
      results. Inhibition of CCDs has been proposed as a remedy, but has not yet found
      its way into the routine diagnostic laboratory. We sought to provide a simple and
      affordable procedure to overcome the CCD problem. METHODS: Serum samples from
      allergic patients were analysed for allergen-specific IgEs by different
      commercial tests (from Mediwiss, Phadia and Siemens) with and without a
      semisynthetic CCD blocker with minimized potential for nonspecific interactions
      that was prepared from purified bromelain glycopeptides and human serum albumin.
      RESULTS: Twenty two per cent of about 6000 serum samples reacted with CCD
      reporter proteins. The incidence of anti-CCD IgE reached 35% in the teenage
      group. In patients with anti-CCD IgE, application of the CCD blocker led to a
      clear reduction in read-out values, often below the threshold level. A much
      better correlation between laboratory results and anamnesis and skin tests was
      achieved in many cases. The CCD blocker did not affect test results where CCDs
      were not involved. CONCLUSION: Eliminating the effect of IgEs directed against
      CCDs by inhibition leads to a significant reduction in false-positive in vitro
      test results without lowering sensitivity towards relevant sensitizations.
      Application of the CCD blocker may be worthwhile wherever natural allergen
      extracts or components are used.

PMID- 24107261
TI  - HIV prevalence in China: integration of surveillance data and a systematic
      review.
AB  - BACKGROUND: Asian HIV epidemics are concentrated among particular behavioural
      groups, but large variations exist in epidemic types, timing, and geographical
      spread between countries and within countries, especially in China. We aimed to
      understand the complexity of HIV epidemics in China by systematically analysing
      prevalence trends by data source, region, population group, and time period.
      METHODS: We collected HIV prevalence data from official national sentinel
      surveillance sites at the provincial level from Jan 1, 1995, to Dec 31, 2010. We
      also searched PubMed, VIP Chinese Journal Database (VIP), China National
      Knowledge Infrastructure, and Wanfang Data from Jan 1, 1990, to Dec 31, 2012, for
      independent studies of HIV prevalence. We integrated both sets of data, and used
      an intraclass correlation coefficient test to assess the similarity of
      geographical pattern of HIV disease burden across 31 Chinese provinces in 2010.
      We investigated prevalence trends (and 95% CIs) to infer corresponding incidence
      by region, population group, and year. FINDINGS: Of 6850 articles identified by
      the search strategy, 821 studies (384,583 drug users, 52,356 injecting drug
      users, 186,288 female sex workers, and 87,834 men who have sex with men) met the
      inclusion criteria. Official surveillance data and findings from independent
      studies showed a very similar geographical distribution and magnitude of HIV
      epidemics across China. We noted that HIV epidemics among injecting drug users
      are decreasing in all regions outside southwest China and have stabilised at a
      high level in northwest China. Compared with injecting drug users, HIV prevalence
      in female sex workers is much lower and has stabilised at low levels in all
      regions except in the southwest. In 2010, national HIV prevalence was 9.08% (95%
      CI 8.04-10.52) in injecting drug users and 0.36% (0.12-0.71) in female sex
      workers, whereas incidence in both populations stabilised at rates of 0.57 (0.43
      0.72) and 0.02 (0.01-0.04) per 100 person-years, respectively. By comparison, HIV
      prevalence in men who have sex with men increased from 1.77% (1.26-2.57) in 2000,
      to 5.98% (4.43-8.18) in 2010, with a national incidence of 0.98 (0.70-1.25) per
      100 person-years in 2010. We recorded strong associations between HIV prevalence
      among at-risk populations in each province, supporting the existence of overlap
      in risk behaviours and mixing among these populations. INTERPRETATION: HIV
      epidemics in China remain concentrated in injecting drug users, female sex
      workers, and men who have sex with men. HIV prevalence is especially high in
      southwest China. Sex between men has clearly become the main route of HIV
      transmission.

PMID- 24107262
TI  - HIV/AIDS trends in China.

PMID- 24107263
TI  - Dynamic kinetic cross-coupling strategy for the asymmetric synthesis of axially
      chiral heterobiaryls.
AB  - A dynamic kinetic asymmetric transformation (DYKAT) technique has been designed
      for the synthesis of 2'-substituted 2-aryl pyridines/isoquinolines and related
      heterobiaryls. In this way, the Pd(0)-catalyzed coupling of racemic 2-triflates
      with aryl boroxines using a TADDOL-derived phosphoramidite as the ligand provides
      the corresponding coupling products with good to excellent enantioselectivities.
      Structural studies support that the formation of configurationally labile
      oxidative addition palladacycles is the key for the success of the methodology. 

PMID- 24107264
TI  - ESCRT requirements for EIAV budding.
AB  - BACKGROUND: Retroviruses and many other enveloped viruses usurp the cellular
      ESCRT pathway to bud from cells. However, the stepwise process of ESCRT-mediated
      virus budding can be challenging to analyze in retroviruses like HIV-1 that
      recruit multiple different ESCRT factors to initiate budding. RESULTS: In this
      study, we characterized the ESCRT factor requirements for budding of Equine
      Infectious Anemia Virus (EIAV), whose only known direct ESCRT protein interaction
      is with ALIX. siRNA depletion of endogenous ESCRT proteins and "rescue"
      experiments with exogenous siRNA-resistant wild type and mutant constructs
      revealed budding requirements for the following ESCRT proteins: ALIX, CHMP4B,
      CHMP2A and VPS4A or VPS4B. EIAV budding was inhibited by point mutations that
      abrogate the direct interactions between ALIX:CHMP4B, CHMP4B:CHMP2A, and
      CHMP2A:VPS4A/B, indicating that each of these interactions is required for EIAV
      budding. Unexpectedly, CHMP4B depletion led to formation of multi-lobed and long
      tubular EIAV virions. CONCLUSIONS: We conclude that EIAV budding requires an
      ESCRT protein network that comprises EIAV Gag-ALIX-CHMP4B-CHMP2A-VPS4
      interactions. Our experiments also suggest that CHMP4B recruitment/polymerization
      helps control Gag polymerization and/or processing to ensure that ESCRT factor
      assembly and membrane fission occur at the proper stage of virion assembly. These
      studies help establish EIAV as a streamlined model system for dissecting the
      stepwise processes of lentivirus assembly and ESCRT-mediated budding.

PMID- 24107265
TI  - The soluble Decoy Receptor 3 is regulated by a PI3K-dependent mechanism and
      promotes migration and invasion in renal cell carcinoma.
AB  - BACKGROUND: Overexpression of Decoy Receptor 3 (DcR3), a soluble member of the
      tumor necrosis factor receptor superfamily, is a common event in several types of
      cancer. In renal cell carcinoma (RCC), DcR3 overexpression is associated with
      lymph node and distant metastasis as well as a poor prognosis. However, the
      functional role and regulation of DcR3 expression in RCC is so far unknown.
      METHODS: Modulation of DcR3 expression by siRNA and ectopic gene expression,
      respectively, was performed in ACHN and 769-P RCC cell lines. Functional effects
      of a modulated DcR3 expression were analyzed with regard to migration, invasion,
      adhesion, clonogenicity, and proliferation. Furthermore, quantitative RT-PCR and
      immunoblot analyses were performed to evaluate the expression of downstream
      mediators of DcR3. In further experiments, luciferase assays, quantitative RT-PCR
      and immunoblot analyses were applied to study the regulation of DcR3 expression
      in RCC. Additionally, an ex vivo tissue slice culture technique combined with
      immunohistochemistry was used to study the regulation of DcR3 expression in human
      RCC specimens. RESULTS: Here, we show that DcR3 promotes adhesion, migration and
      invasiveness of RCC cells. The DcR3-dependent increase in cellular invasiveness
      is accompanied with an up-regulation of integrin alpha 4, matrixmetalloproteinase
      7 and urokinase plasminogen activator (uPA). Further, we identified a signaling
      pathway regulating DcR3 expression in RCC. Using in vitro experiments as well as
      an ex vivo RCC tissue slice culture model, we demonstrate that expression of DcR3
      is regulated in a PI3K/AKT-dependent manner involving the transcription factor
      nuclear factor of activated T-cells (NFAT). CONCLUSIONS: Taken together, our
      results identify DcR3 as a key driver of tumor cell dissemination and suggest
      DcR3 as a promising target for rational therapy of RCC.

PMID- 24107266
TI  - In utero exposure to benzo[a]pyrene increases adiposity and causes hepatic
      steatosis in female mice, and glutathione deficiency is protective.
AB  - Polycyclic aromatic hydrocarbons (PAHs), including benzo[a]pyrene (BaP), are
      ubiquitous environmental pollutants found in tobacco smoke, air pollution, and
      grilled foods. Reactive metabolites and reactive oxygen species generated during
      PAH metabolism are detoxified by reactions involving glutathione (GSH). Early
      life exposures to tobacco smoke and air pollution have been linked to increased
      risk of obesity and metabolic syndrome. We investigated the independent and
      interactive effects of prenatal exposure to BaP and GSH deficiency due to
      deletion of the modifier subunit of glutamate cysteine ligase (Gclm), the rate
      limiting enzyme in GSH synthesis, on adiposity and hepatic steatosis in adult
      female F1 offspring. We mated Gclm(+/-) dams with Gclm(+/-) males and treated the
      pregnant dams with 0, 2, or 10mg/kg/day BaP in sesame oil by oral gavage daily
      from gestational day 7 through 16. We analyzed metabolic endpoints in female
      Gclm(-/-) and Gclm(+/+) littermate F1 offspring. Prenatal BaP exposure
      significantly increased visceral adipose tissue weight, weight gain between 3
      weeks and 7.5 months of age, hepatic lipid content measured by oil red O
      staining, and hepatic fatty acid beta-oxidation gene expression in Gclm(+/+), but
      not in Gclm(-/-), female offspring. Hepatic expression of lipid biosynthesis and
      antioxidant genes were decreased and increased, respectively, in Gclm(-/-) mice.
      Our results suggest that reported effects of pre- and peri-natal air pollution
      and tobacco smoke exposure on obesity may be mediated in part by PAHs. GSH
      deficiency is protective against the metabolic effects of prenatal BaP exposure. 

PMID- 24107267
TI  - OnabotulinumtoxinA for chronic migraine: efficacy, safety, and tolerability in
      patients who received all five treatment cycles in the PREEMPT clinical program.
AB  - OBJECTIVE: Chronic migraine (CM) is a prevalent and disabling neurological
      disorder. Phase III REsearch Evaluating Migraine Prophylaxis Therapy (PREEMPT)
      clinical program assessed efficacy and safety of onabotulinumtoxinA (BOTOX((r)))
      for prophylaxis of headaches in adults with CM. This secondary analysis assessed
      patients who received all five treatment cycles and completed the study.
      MATERIALS AND METHODS: PREEMPT (two phase III studies: 24-week double-blind,
      placebo-controlled [DBPC], parallel-group phase, followed by 32-week open-label
      [OL] phase) evaluated the efficacy and safety of onabotulinumtoxinA in CM (>=15
      days/month with headache lasting >=4 h a day). Patients were randomized (1:1) to
      onabotulinumtoxinA or placebo every 12 weeks for two cycles, followed by
      onabotulinumtoxinA for three cycles. Multiple headache symptom measures were
      evaluated. Results for the completer (five cycles) subgroup of patients are
      reported. RESULTS: Of 1384 total PREEMPT patients, 1005 received all five
      treatment cycles (513 received onabotulinumtoxinA only
      [onabotulinumtoxinA/onabotulinumtoxinA (O/O)] and 492 received two cycles of
      placebo then three cycles of onabotulinumtoxinA [placebo/onabotulinumtoxinA
      (P/O)]). Demographics were similar between treatment groups. At Week 56, after
      all patients were treated with onabotulinumtoxinA, there continued to be
      significant between-group differences favoring the O/O vs P/O group for the
      following headache symptom measures: LS mean change from baseline in frequencies
      of headache days (-12.0 O/O, -11.1 P/O; P = 0.035), migraine days (-11.6 O/O, 
      10.7 P/O; P = 0.038), and moderate/severe headache days (-11.0 O/O, -10.1 P/O; P
      = 0.042). For other measures (cumulative hours of headache on headache days,
      frequency of headache episodes, and percentage with severe Headache Impact Test
      (HIT)-6 score, and total HIT-6 and Migraine-Specific Quality of Life
      Questionnaire scores), there were also large mean improvements from baseline. The
      percent of patients with a >=50% reduction from baseline in frequency of headache
      days was significantly greater for the onabotulinumtoxinA-only group at Week 56
      (69.6% O/O, 62.8% P/O; P = 0.023). The treatment-related adverse event rate was
      28.5% for onabotulinumtoxinA vs 12.4% for placebo in the DBPC phase and 34.8% for
      patients treated with onabotulinumtoxinA for all five cycles throughout the 56
      week trials. CONCLUSIONS: This subgroup analysis demonstrated improvements with
      onabotulinumtoxinA treatment (five cycles) vs placebo (two
      cycles)/onabotulinumtoxinA (three cycles) for multiple headache symptom measures
      and suggests that at Week 56, patients treated earlier with onabotulinumtoxinA
      had better outcomes. These findings demonstrate the continued need and cumulative
      benefit over time with continued prophylaxis, an important and clinically
      pragmatic observation for clinicians and patients.

PMID- 24107269
TI  - Discrepancies between guidelines and clinical practice regarding prostate
      specific antigen testing.
AB  - BACKGROUND: Most guidelines recommend a judicious use of prostate-specific
      antigen (PSA) testing, whereas in daily practice, an increase of the incidence of
      PSA testing has been shown. Accurate up-to-date PSA test incidence rates are,
      however, lacking. OBJECTIVE: To investigate the PSA test incidence rates in
      general practices over the past 10 years and to study which factors are
      associated with more frequent test use. METHODS: We performed a retrospective
      cohort study using the routine health care database of the Julius General
      Practitioners Network from 2002 to 2011, of which data were available from more
      than 65 000 male patients. We calculated the annual incidence of PSA testing
      rates per 1000 person-years. Co-morbidities were analysed by means of
      International Classification of Primary Care codes. Relative risks (RRs) of
      having a PSA test were estimated as the ratio of observed rates of co-morbidities
      in men who underwent the test compared with a control group, and 95% confidence
      intervals (CI) were calculated. RESULTS: From 2002 to 2011, the overall incidence
      rate of PSA testing in men >=45 years increased almost 4-fold, from 15.5 to 54.3
      per 1000 person-years. As from 2005, the incidence rates appear to increase more
      than those before 2005. Men with cardiovascular diseases, joint disorders,
      psychiatric diseases, respiratory diseases, overweight and diabetes mellitus were
      predisposed to undergo a PSA test, but men with urinary problems had the highest
      relative risk (RR 1.77, 95% CI 1.72-1.82). CONCLUSIONS: From 2002 to 2011, PSA
      incidence testing rates increased, particularly in men with urinary symptoms and
      cardiovascular disease, despite several international guidelines that suggest a
      judicious use of PSA tests.

PMID- 24107268
TI  - Impact of diets with a high content of greaves-meal protein or carbohydrates on
      faecal characteristics, volatile fatty acids and faecal calprotectin
      concentrations in healthy dogs.
AB  - BACKGROUND: Research suggests that dietary composition influences
      gastrointestinal function and bacteria-derived metabolic products in the dog
      colon. We previously reported that dietary composition impacts upon the faecal
      microbiota of healthy dogs. This study aims at evaluating the dietary influences
      on bacteria-derived metabolic products associated with the changes in faecal
      microbiota that we had previously reported. We fed high-carbohydrate starch based
      (HCS), [crude protein: 194 g/kg, starch: 438 g/kg], high-protein greaves-meal
      (HPGM), [crude protein: 609 g/kg, starch: 54 g/kg] and dry commercial (DC),
      [crude protein: 264 g/kg, starch: 277 g/kg] diets, and studied their effects on
      the metabolism of the colonic microbiota and faecal calprotectin concentrations
      in five Beagle dogs, allocated according to the Graeco-Latin square design. Each
      dietary period lasted for three weeks and was crossed-over with washout periods.
      Food intake, body weight, and faecal consistency scores, dry matter, pH, ammonia,
      volatile fatty acids (VFAs), and faecal canine calprotectin concentrations were
      determined. RESULTS: Faecal ammonia concentrations decreased with the HCS diet.
      All dogs fed the HPGM diet developed diarrhoea, which led to differences in
      faecal consistency scores between the diets. Faecal pH was higher with the HPGM
      diet. Moreover, decreases in propionic and acetic acids coupled with increases in
      branched-chain fatty acids and valeric acid caused changes in faecal total VFAs
      in dogs on the HPGM diet. Faecal canine calprotectin concentration was higher
      with the HPGM diet and correlated positively with valeric acid concentration.
      CONCLUSIONS: The HPGM diet led to diarrhoea in all dogs, and there were
      differences in faecal VFA profiles and faecal canine calprotectin concentrations.

PMID- 24107270
TI  - Parents' views and experiences when their preschool child is identified as
      overweight: a qualitative study in primary care.
AB  - BACKGROUND: Prevalence of overweight in children has increased significantly in
      many countries in the past decades. Few parents identify their own children as
      overweight, especially very young children. Motivating parents is difficult, and
      interventions to attain normal weight often fail. OBJECTIVE: To explore parents'
      views and experiences when health professionals identify their preschool child as
      overweight. METHODS: In-depth interviews were held with parents of 10 overweight
      children aged 2.5-5.5 years. Parents were recruited at well child clinics in
      rural parts of eastern Norway. Interviews were recorded digitally, transcribed
      verbatim and analysed thematically. RESULTS: Parents presented themselves and
      their toddlers as vulnerable. To protect their child from developing low self
      esteem and eating disorders, some parents preferred their child not to be present
      when discussing overweight. Growth charts were looked upon as objective and
      useful. Parents talked readily about their own weight experiences. Being
      overweight themselves represented both a barrier to, and motivation for, dealing
      with their toddler's overweight. Parents appreciated support from professionals
      in kindergarten, but grandparents often undermined the parents' effort to make
      changes. CONCLUSIONS: Early childhood overweight should be addressed in a
      sensitive and respectful manner and should consider whether the index child
      should be present during discussion. It may be helpful for clinicians to discuss
      parents' own weight and dieting experiences and concerns about eating disorders.
      All the child's caretakers should be considered a target for intervention, and
      grandparents and kindergarten professionals should be included.

PMID- 24107271
TI  - Pharmacognostic standardization with various plant parts of Desmostachya
      bipinnata.
AB  - CONTEXT: Desmostachya bipinnata (L.) Stapf [Gramineae (Poaceae)] has been
      traditionally used to treat various disorders such as asthma, kidney stone,
      diarrhea, wound healing, etc. OBJECTIVE: The present study involves
      pharmacognostic, botanical, and preliminary phytochemical examination of various
      plant parts and powders of D. bipinnata. MATERIALS AND METHODS: Leaves, stem,
      roots, underground and aerial part powders were microscopically examined.
      Pharmacognostic standardization parameters were determined as per the WHO
      guidelines. Parameters, including extractive value in different solvents, ash
      values, and loss on drying, were determined. Preliminary phytochemical studies,
      fluorescence analysis, and chromatographic profiling were performed for the
      correct identification of this crude drug and some of its phytoconstituents.
      RESULTS: Microscopical studies showed various characteristic features including,
      collateral vascular bundle, bundle sheath cells, and bulliform cells in leaf,
      conjoint, collateral and closed vascular bundles, and sclerenchymatous sheath in
      stem; and silica bodies in root. Phytochemical screening and chromatographic
      profile of aerial plant parts revealed the presence of alkaloids, tannins,
      flavonoids, steroids, glycosides, and coumarins. Underground plants parts
      indicated the presence of glycosides, steroids, flavonoids, coumarins, and
      alkaloids. DISCUSSION AND CONCLUSION: The results of the performed studies are
      helpful in correct identification, characterisation of D. bipinnata. Preliminary
      phytochemical studies and chromatographic profiling may be helpful in further
      isolation and purification of lead compounds from different extracts.

PMID- 24107274
TI  - Effective combination therapy of polymyxin-B direct hemoperfusion and recombinant
      thrombomodulin for septic shock accompanied by disseminated intravascular
      coagulation: a historical controlled trial.
AB  - Disseminated intravascular coagulation (DIC) and multiple organ failure often
      occur via the crosstalk between inflammation and coagulation, which is mediated
      by High Mobility Group Box 1 (HMGB1). In septic shock, Polymyxin-B direct
      hemoperfusion (PMX-DHP) ameliorates hemodynamics by endogenous cannabinoid
      adsorption and improves pulmonary oxygenation by indirect cytokine reduction
      through the adsorption of activated mononuclear cells. However, PMX-DHP has no
      direct effect on HMGB1 circulating in the plasma. In cases with DIC, recombinant
      thrombomodulin (rTM), an effective drug for DIC, exerts not only anticoagulation
      but also antiinflammatory properties via direct anti-HMGB1 activity. Therefore, a
      combination of PMX-DHP and rTM is expected to block the vicious cycle of a
      cytokine storm ending up with multiple organ failure in DIC. The aim of this
      study was to investigate the efficacy of combination therapy for septic shock
      associated with DIC. This study comprised 22 consecutive patients with sepsis
      induced DIC who received PMX-DHP. The initial eight patients were treated without
      rTM (historical control group), and the following 14 patients were given rTM (rTM
      group). The baseline Sequential Organ Failure Assessment (SOFA) score or age was
      not different between both groups. Sixty-day survival rate in the rTM group was
      significantly higher than that in the control group (85.7% vs. 37.5%, P = 0.015).
      A combination of PMX-DHP and rTM may be effective in septic shock accompanied by
      DIC and is expected to improve survival rates. 

PMID- 24107275
TI  - Granulocyte and monocyte adsorption apheresis for refractory skin diseases due to
      activated neutrophils, psoriasis, and associated arthropathy.
AB  - Granulocyte and monocyte adsorption apheresis (GMA), an extracorporeal apheresis
      instrument whose column contains cellulose acetate (CA) beads, is designed to
      remove activated granulocytes and monocytes. We previously demonstrated that GMA
      was useful for treating neutrophilic dermatoses and associated arthropathy as it
      adsorbs Mac-1 (CD11b/CD18)-expressing neutrophils to the CA beads by the binding
      of complement component (iC3b) and CD11b expressed on activated neutrophils. The
      objective of this study is to further assess the clinical effectiveness of GMA in
      the treatment of neutrophilic dermatoses and associated arthropathy. The effect
      of GMA for skin lesions and joint lesions was assessed in 44 and 23 patients,
      respectively. Mac-1 expression on peripheral neutrophils was measured by flow
      cytometry. Skin lesions and arthropathy improved in 39 of 44 patients (88.6%) and
      22 of 23 (95.6%), respectively. Mac-1 (CD11b/CD18) expression on the peripheral
      neutrophils, 27.1 +/- 6.66 MFI (mean fluorescence intensity) before treatment,
      was reduced to 17.9 +/- 3.02 MFI by GMA (P < 0.05). Clinical effectiveness of GMA
      for the treatment of intractable neutrophilic dermatoses and associated
      arthropathy was further confirmed. 

PMID- 24107276
TI  - Solute removal capacity of high cut-off membrane plasma separators.
AB  - In vitro blood filtration was performed by a closed circuit using high cut-off
      membrane plasma separators, EVACURE EC-2A10 (EC-2A) and EVACURE EC-4A10 (EC-4A).
      Samples were obtained from sampling sites before the plasma separator, after each
      plasma separator, and from the ultrafiltrate of each separator. The sieving
      coefficient (S.C.) of total protein (TP), albumin (Alb), IgG, interleukin-6 (IL
      6), interleukin-8 (IL-8), tumor necrosis factor-alpha (TNF-alpha), fibrinogen
      (Fib), antithrombin III (AT-III), and coagulation factor XIII (FXIII) were
      calculated. The S.C. of each solute using EC-2A and EC-A4 were as follows; TP:
      0.25 and 0.56, Alb: 0.32 and 0.73, IgG: 0.16 and 0.50, IL-6:0.73 and 0.95, IL
      8:0.85 and 0.82, TNF-alpha: 1.07 and 0.99, Fib: 0 and 0, FXIII: 0.07 and 0.17,
      respectively. When compared with the conventional type of membrane plasma
      separators, EVACURE could efficiently remove cytokines while retaining
      coagulation factors such as fibrinogen. Moreover, EC-2A prevented protein loss,
      whereas EC-4A could remove approximately 50% of IgG. 

PMID- 24107277
TI  - Questionnaire based assessment of patients' acceptability of leukocytapheresis
      for the treatment of inflammatory bowel disease.
AB  - The aim of the present study was to assess patients' acceptance of therapeutic
      leukocytapheresis known as cytapheresis (CAP) for the treatment of an active
      flare of inflammatory bowel disease (IBD). A questionnaire was sent to 155 IBD
      patients who had been treated with CAP for an active flare of IBD at the IBD
      center of Hyogo College of Medicine between January 2009 and July 2012. In the
      questionnaire, patients were asked to evaluate CAP including efficacy, safety,
      unfavorable features and their willingness to be retreated with CAP for a
      subsequent IBD flare-up. Seventy-eight percent (112 of 155 patients) including 86
      with ulcerative colitis and 26 with Crohn's disease completed the questionnaire.
      The need for coming to hospital for CAP, needle pain during blood access, sparing
      time for CAP process were scored by 57%, 58%, and 58.9% of the patients,
      respectively as unfavorable. Patients highly favored the safety of CAP, the sum
      of very and relatively favorable was 89%, higher than for efficacy (68%). Seventy
      two percent of patients favored retreatment with CAP. In binary logistic
      regression analysis, the levels of satisfaction for efficacy (P < 0.001), and
      inconvenience for CAP treatment time (P < 0.001) were highly significant factors
      for patients' willingness to be retreated. Bearing in mind that CAP is a non
      pharmacologic treatment intervention, our analyses indicated that IBD patients
      favored high efficacy, as well as comfort of CAP or maintaining their normal
      social activity even during an active phase of the disease. Patient's
      acceptability for CAP appeared to be determined by the balance of these factors. 

PMID- 24107278
TI  - Hemoglobin maintenance and dosing strategies using intravenous continuous
      erythropoietin receptor activator in Japanese hemodialysis patients.
AB  - Methoxy polyethylene glycol-epoetin beta, a continuous erythropoietin receptor
      activator (CERA), is reported to be effective in managing renal anemia but there
      is little data about CERA in Japan. This study aimed to ascertain the effects of
      CERA in Japanese hemodialysis patients and the appropriate starting dose of CERA
      when switching from other erythropoiesis-stimulating agents. We switched 61
      stable hemodialysis patients to 4-weekly intravenous CERA, from either epoetin
      beta (rHuEPO) or darbepoetin alpha (DA). When determining the initial dose of
      CERA, we used guidelines recommended by the Japanese supplier for switching from
      rHuEPO, but for DA we based the CERA dose on European reports, because no
      Japanese guidelines exist. Fifty-two patients completed the 28-week study.
      Hemoglobin was maintained within the target range (10.0-12.0 g/dL). The required
      CERA dose decreased over the 28 weeks. The hemoglobin level and CERA dose
      stabilized faster when switching from DA. CERA showed similar efficacy in
      diabetic and non-diabetic patients. The effect of CERA is similar regardless of
      whether patients switch from low- or high-dose erythropoiesis-stimulating agents.
      In conclusion, CERA is effective for Japanese hemodialysis patients at a lower
      dose than expected. 

PMID- 24107279
TI  - Strategies for the creation and maintenance of reconstructed arteriovenous
      fistulas using the forearm basilic vein.
AB  - Reconstruction of an arteriovenous fistula (AVF) after an initial failure to
      provide long-term patency has been desired in the era when hemodialysis patients'
      prognosis is improving. The forearm basilic vein AVF should be considered, before
      an artificial graft shunt or an AVF in the cubital region. The present study was
      designed to establish a strategy for the creation and maintenance of AVFs using
      the forearm basilic vein. This study reviewed 76 cases of reconstructed AVF
      including 18 cases using the basilic vein (23.7% of total cases). The following
      four points were considered: arm positioning of the cubital flexion position
      combined with the forearm supinated position; several small skin incisions with a
      subcutaneous tunnel; sufficient venous dilatation using Fogarty balloon catheter;
      and early percutaneous angioplasty introduction for immature AVF. The primary and
      secondary patency rates were examined. A radiobasilic AVF was created through a
      subcutaneous tunnel in two cases. The primary and secondary patency rates of AVF
      with the basilic vein were 54.7% and 76.7% respectively, whereas those of AVF
      with the cephalic vein were 49.3% and 71.3%. The basilic was not inferior to the
      cephalic vein (P-value of the log-rank test for primary and secondary patency
      rates were 0.927 and 0.811, respectively). Early stage percutaneous angioplasty
      was effective in five cases with immature AVF. The forearm basilic vein was
      useful in AVF reconstruction and equivalent to radiocephalic reconstruction.
      Careful observation and percutaneous angioplasty during the early period after
      the surgery were essential for long-term patency. 

PMID- 24107280
TI  - Impact of different types of resuscitation fluids on coagulation and continuous
      venovenous hemofiltration hemocompatibility in a porcine model.
AB  - Intensive therapy demanding diseases (organ failure or sepsis) are assumed to be
      the etiology behind a decreased biocompatibility of extracorporeal systems for
      renal replacement therapy (RRT). There are also potential interactions between
      different components of the overall therapy. Volume substitutes are known to
      influence hemorheology and coagulation. To define a potential net effect of
      volume substitutes on the hemocompatibility of an RRT, we chose an animal model
      without interfering pathophysiologies. According to the problem of early filter
      failure and coagulation disorders in critically ill patients, we focused on the
      hypothesized interaction between RRT and different volume substitutes with
      respect to blood cell counts, coagulation parameters and required heparin dose.
      Forty-eight pigs were assigned to four groups of fluid therapy with either normal
      saline (NaCl), 6%HES130kD/0.4 (HES130), 6%HES200kD/0.5 (HES200) or 4%gelatin
      (GEL). Six pigs of each fluid group underwent continuous venovenous
      hemofiltration (CVVH), the remaining six served as the control group.
      Anticoagulation was performed with continuous heparin infusion. CVVH was run in a
      recirculation-mode for 4.5 h to force hemocompatibility reactions, thereafter in
      a standard-mode for 2 h. During the CVVH-treatment GEL reduced platelet counts
      and fibrinogen concentration and additionally lowered ATIII levels. Heparin
      requirements did not differ between different volume substitutes or CVVH and
      control groups. Severe pathophysiologies are not the only reason for a reduced
      hemocompatibility of CVVH treatment. Interaction of a particular volume
      substitute with CVVH should be considered when interpreting study results and
      evolving new strategies. 

PMID- 24107281
TI  - Long-term antihypertensive effects of aliskiren, a direct renin inhibitor, in
      chronic hemodialysis patients.
AB  - The renin-angiotensin-aldosterone system is not necessarily suppressed in end
      stage renal disease patients undergoing dialysis. Of all the inhibitors of this
      system, the clinical efficacy of the renin inhibitor, aliskiren, has not been
      well demonstrated in dialysis patients. We evaluated the antihypertensive effect
      of aliskiren, administered as a single daily dose of 150 mg for 24 weeks, in 23
      chronic hemodialysis patients (age 65 +/- 12 years, 15 men and eight women) with
      blood pressure >=140/90 mm Hg, and assessed the factors relating to blood
      pressure reduction. At 4 weeks, the average systolic blood pressure before the
      dialysis session was insignificantly reduced from 163 +/- 10 mm Hg to 160 +/- 15
      mm Hg, while it was significantly lowered at 12 (154 +/- 13 mm Hg) and 24 weeks
      (155 +/- 10 mm Hg), although the pulse rate was not significantly altered. Serum
      K increased at 24 weeks from 4.9 +/- 0.6 mEq/L to 5.2 +/- 0.8 mEq/L. Only 10 out
      of 23 patients showed systolic blood pressure reduction by >=10 mm Hg. Naturally,
      plasma renin immunoreactivity increased, while plasma renin activity, along with
      angiotensin II and aldosterone levels decreased. Basal levels of the components
      of the renin-angiotensin-aldosterone system were not significantly different in
      patients showing systolic blood pressure reduction by >=10 mm Hg (n = 10) vs.
      those with <10 mm Hg changes (n = 13). The reduction in systolic blood pressure
      in all 23 patients taken as a whole correlated with changes in plasma renin
      activity (r = -0.432, P < 0.05) and angiotensin II (r = 0.467, P < 0.05). In
      chronic hemodialysis patients, aliskiren modestly lowers blood pressure over the
      long term, although the antihypertensive effect seems dependent on the changes,
      but not on the basal levels of plasma renin activity and angiotensin II. 

PMID- 24107282
TI  - Conceptual framework for holistic dialysis management based on key performance
      indicators.
AB  - This paper develops a theoretical framework of holistic hospital management based
      on performance indicators that can be applied to dialysis hospitals, clinics or
      departments in Japan. Selection of a key indicator set and its validity tests
      were performed primarily by a questionnaire survey to dialysis experts as well as
      their statements obtained through interviews. The expert questionnaire asked
      respondents to rate the degree of "usefulness" for each of 66 indicators on a
      three-point scale (19 responses collected). Applying the theoretical framework,
      we selected a minimum set of key performance indicators for dialysis management
      that can be used in the Japanese context. The indicator set comprised 27
      indicators and items that will be collected through three surveys: patient
      satisfaction, employee satisfaction, and safety culture. The indicators were
      confirmed by expert judgment from viewpoints of face, content and construct
      validity as well as their usefulness. This paper established a theoretical
      framework of performance measurement for holistic dialysis management from
      primary healthcare stakeholders' perspectives. In this framework, performance
      indicators were largely divided into healthcare outcomes and performance shaping
      factors. Indicators of the former type may be applied for the detection of
      operational problems or weaknesses in a dialysis hospital, clinic or department,
      while latent causes of each problem can be more effectively addressed by the
      latter type of indicators in terms of process, structure and culture/climate
      within the organization. 

PMID- 24107283
TI  - Clinicopathological analysis of persistent hypercalcemia and hyperparathyroidism
      after kidney transplantation in long-term dialysis patients.
AB  - Deceased donor kidney transplantation in long-term dialysis patients in Japan has
      been increasing because of a severe lack of donors. Parathyroid glands of long
      term dialysis patients often show qualitative morphological changes from diffuse
      to nodular hyperplasia. Only a few studies have reported the clinicopathological
      analysis of persistent hyperparathyroidism after kidney transplantation in long
      term (>10 years) dialysis patients. This study on consecutive deceased donor
      kidney transplantation performed from 2002 to 2010 measured biochemical
      parameters related to bone and mineral disorders and examined parathyroid tissues
      in parathyroidectomy cases. Thirty-four subjects (22 males; mean age, 53.8 +/-
      7.9 years; mean dialysis period, 14.4 +/- 4.3 years) were enrolled. Multivariate
      analysis of potential predictors for the hypercalcemia group at 12 months after
      transplantation showed that pre-transplantation and early post-transplantation
      calcium and parathyroid hormone levels were significant determinants.
      Pathological examination showed that a number of glands showed nodular
      hyperplasia, even in small glands weighing < 100 mg. In long-term dialysis
      patients, hyperparathyroidism and hypercalcemia developed at an early stage after
      transplantation and persisted for a long period (>4 years), with nodular
      hyperplasia being found even in low-weight parathyroid glands. Pre-transplant
      high calcium and parathyroid hormone levels were the predictors for the prolonged
      hypercalcemia. Persistent hyperparathyroidism was considered to be caused by
      remaining nodular hyperplasia, even if the glands were small. Although the best
      treatment option is to perform a parathyroidectomy in the waiting period before
      transplantation, we suggest that it be performed in cases with prolonged
      hypercalcemia of >6 months after transplantation. 

PMID- 24107285
TI  - Involvement of extracellular signal-regulated kinase in leukocyte adsorption
      induced production of hepatocyte growth factor.

PMID- 24107284
TI  - Enhanced vascular endothelial growth factor and inflammatory cytokine removal
      with online hemodiafiltration over high-flux hemodialysis in sepsis-related acute
      kidney injury patients.
AB  - Hypercytokinemia plays a central role in pathogenesis and is related to the high
      mortality in sepsis-related acute kidney injury (AKI). Besides the established
      cytokines, vascular endothelial growth factor (VEGF) is demonstrated as an
      important factor in enhancing vascular leakage in sepsis. This prospective
      randomized trial was conducted to compare the efficacy of cytokine removal
      between online hemodiafiltration (HDF), which combines convective and diffusive
      solute removal, and high-flux hemodialysis (HD). Twenty-eight sepsis-related AKI
      patients were included and randomized into online HDF and high-flux HD. The
      percentages of the reduction ratio in plasma cytokines were measured as primary
      outcomes. Other clinical parameters were determined as secondary outcomes. When
      compared with high-flux HD, online HDF provided significantly greater percentages
      of the reduction ratio in plasma cytokine levels, including VEGF (P < 0.001), IL
      6 (P = 0.001), IL-8 (P = 0.021), IL-10 (P = 0.011), and tumor necrosis factor
      alpha (P = 0.029). There were no significant differences in intradialytic blood
      pressures. Online HDF revealed better renal recovery and shorter length of
      hospitalization than high-flux HD. In conclusion, online HDF in sepsis-related
      AKI could provide significantly better removal of VEGF and other cytokines and
      these were associated with better renal outcome than high-flux HD. Thus, online
      HDF would offer a potential role in hypercytokinemic state in sepsis-related AKI.

PMID- 24107290
TI  - Challenges of cognitive research in neurofibromatosis type 1.

PMID- 24107289
TI  - Estimating the incidence reporting rates of new influenza pandemics at an early
      stage using travel data from the source country.
AB  - During the surveillance of influenza pandemics, underreported data are a public
      health challenge that complicates the understanding of pandemic threats and can
      undermine mitigation efforts. We propose a method to estimate incidence reporting
      rates at early stages of new influenza pandemics using 2009 pandemic H1N1 as an
      example. Routine surveillance data and statistics of travellers arriving from
      Mexico were used. Our method incorporates changes in reporting rates such as
      linearly increasing trends due to the enhanced surveillance. From our results,
      the reporting rate was estimated at 0.46% during early stages of the pandemic in
      Mexico. We estimated cumulative incidence in the Mexican population to be 0.7%
      compared to 0.003% reported by officials in Mexico at the end of April. This
      method could be useful in estimation of actual cases during new influenza
      pandemics for policy makers to better determine appropriate control measures.

PMID- 24107291
TI  - A need for new treatments in narcolepsy.

PMID- 24107293
TI  - Arginine vasotocin neuronal phenotype and interspecific cooperative behaviour.
AB  - The nonapeptide arginine vasotocin (AVT) and its mammalian homologue arginine
      vasopressin are well known for their role in the modulation of several
      intraspecific social behaviours, such as social approach/withdrawal and
      aggression. Recently, we suggested that AVT might also be important in the
      regulation of interspecific social behaviours as it modulates interspecific
      cooperative behaviours in the Indo-Pacific bluestreak cleaner wrasse Labroides
      dimidiatus. AVT injections decreased cleaners' propensity to engage in cleaning
      interactions with their clients, suggesting that high levels of this peptide
      compromise the cleaners' cooperative motivation. Therefore, we hypothesise that
      low endogenous levels of AVT are a prerequisite for the expression of
      interspecific cleaning behaviour in cleaner wrasses, since it allows them to
      approach and interact with interspecific individuals, and that this should be
      reflected in their AVT neuronal phenotype. Here we test this hypothesis by
      comparing the AVT neuronal phenotypes of two phylogenetically closely related
      species that live in similar environments but diverge in the expression of
      interspecific cooperative behaviour: an obligate cleaner wrasse (L. dimidiatus)
      and a non-cleaner corallivore wrasse (Labrichthys unilineatus). The two species
      are predicted to differ in their AVT neuronal phenotypes as a reflection of their
      ability/inability to approach and interact with interspecific individuals, with
      cleaners presenting smaller and/or less numerous AVT-immunoreactive (ir) neurons.
      A sex difference in AVT neuronal phenotypes was also predicted because males of
      both species appear to be more aggressive than females. As described for most of
      the other teleost species, AVT-ir neurons were restricted to the preoptic area,
      and in agreement with our first prediction cleaners presented smaller and less
      numerous AVT-ir neurons in the gigantocellular preoptic area (gPOA) compared to
      non-cleaners. Contrary to our second prediction, AVT neuronal phenotypes did not
      differ between sexes in either species, but differences in other features of the
      AVT system cannot be ruled out. In summary, the results presented here suggest a
      putative role for AVT gPOA neurons in the ability of a cleaner wrasse to approach
      and interact with a client, through their projections to extrahypothalamic brain
      areas.

PMID- 24107295
TI  - SIRT1 is downregulated in gastric cancer and leads to G1-phase arrest via NF
      kappaB/Cyclin D1 signaling.
AB  - Sirtuin 1 (SIRT1) is a class III histone/protein deacetylase, and its activation
      status has been well documented to have physiologic benefits in human health.
      However, the function of SIRT1 in cancer remains controversial. Here, the
      expression and role of SIRT1 in gastric cancer is delineated. SIRT1 was present
      in all normal gastric mucosa specimens; however, it was only present in a portion
      of the matched gastric cancer tumor specimens. In SIRT1-positive tumors, both
      mRNA and protein levels were downregulated as compared with the corresponding
      nonneoplastic tissue. Ectopic expression of SIRT1 inhibited cell proliferation,
      diminished clonogenic potential, and induced a G1-phase cell-cycle arrest, the
      effects of which were not apparent when a catalytic-domain mutant form of SIRT1
      was introduced, suggesting that SIRT1 functions in gastric cancer are dependent
      on its deacetylase activity. Further evidence was obtained from depletion of
      SIRT1. At the molecular level, SIRT1 inhibited the transcription of Cyclin D1
      (CCND1), and inhibition of NF-kappaB in SIRT1-depleted cells rescued Cyclin D1
      expression. Furthermore, inhibition of either NF-kappaB or Cyclin D1 in SIRT1
      depleted cells reversed the inhibitory effects of SIRT1. The inhibitory role of
      SIRT1 was also verified in vivo using xenografts. This work characterizes SIRT1
      status and demonstrates its inhibitory function in gastric cancer development,
      which involves NF-kappaB/Cyclin D1 signaling, offering a therapeutic role for
      SIRT1 activators. IMPLICATIONS: The inhibitory functions of SIRT1, which involve
      NF-kappaB/Cyclin D1 signaling, suggest the utility of SIRT1 activators in the
      prevention and therapy of gastric cancer.

PMID- 24107292
TI  - Pitolisant versus placebo or modafinil in patients with narcolepsy: a double
      blind, randomised trial.
AB  - BACKGROUND: Narcolepsy is characterised by excessive daytime sleepiness (EDS) and
      cataplexy. Histamine neurons are crucial to maintain wakefulness. We assessed the
      safety and efficacy of pitolisant (previously called BF2.649), a selective
      histamine H3 receptor inverse agonist that activates these neurons, in patients
      with narcolepsy. METHODS: For this double-blind, randomised, parallel-group
      controlled trial, we recruited patients with narcolepsy from 32 sleep disorder
      centres in five European countries. Patients were eligible if they were aged 18
      years or older, had not taken psychostimulants for at least 14 days, and had EDS
      (defined as an Epworth Sleepiness Scale [ESS] score of at least 14). Using a
      computer-generated randomisation sequence, we randomly allocated patients to
      receive pitolisant, modafinil, or placebo (1:1:1). Treatment lasted 8 weeks: 3
      weeks of flexible dosing according to investigator's judgment (10 mg, 20 mg, or
      40 mg a day of pitolisant; 100 mg, 200 mg or 400 mg a day of modafinil) followed
      by 5 weeks of stable dosing. Patients took four tablets a day in a double-dummy
      design to ensure masking. For the primary analysis, assessed in the intention-to
      treat population, we assessed the superiority of pitolisant versus placebo, and
      the non-inferiority of pitolisant versus modafinil. This trial is registered with
      ClinicalTrials.gov, number NCT01067222. FINDINGS: Between May 26, 2009, and June
      30, 2010, we screened 110 patients, 95 of whom were eligible and randomly
      assigned to treatment: 30 to placebo, 32 to pitolisant, and 33 to modafinil. Over
      the 8-week treatment period, mean ESS score reductions were -3.4 (SD 4.2) in the
      placebo group, -5.8 (6.2) in the pitolisant group, and -6.9 (6.2) in the
      modafinil group. Our primary analysis of between-group differences in mean ESS
      score at endpoint (adjusted for baseline) showed pitolisant to be superior to
      placebo (difference -3.0, 95% CI -5.6 to -0.4; p=0.024), but not non-inferior to
      modafinil (difference 0.12, 95% CI -2.5 to 2.7; p=0.250). We recorded 22 adverse
      events with pitolisant, 26 with modafinil, and ten with placebo. Six severe
      adverse events were treatment-related: one with pitolisant (abdominal discomfort)
      and five with modafinil (abdominal pain, abnormal behaviour, amphetamine-like
      withdrawal symptoms, lymphoadenopathy, and inner ear disorders). INTERPRETATION:
      Pitolisant at doses up to 40 mg was efficacious on EDS compared with placebo and
      well tolerated compared with modafinil. If these findings are substantiated in
      further studies, pitolisant could offer a new treatment option for patients with
      narcolepsy. FUNDING: Bioprojet, France.

PMID- 24107296
TI  - S100A14: novel modulator of terminal differentiation in esophageal cancer.
AB  - Aberrant keratinocyte differentiation is a key mechanism in the initiation of
      cancer. Because activities regulating differentiation exhibit altered or reduced
      capacity in esophageal cancer cells, it is vital to pinpoint those genes that
      control epidermal proliferation and terminal differentiation to better understand
      esophageal carcinogenesis. S100A14 is a member of the S100 calcium-binding
      protein family and has been suggested to be involved in cell proliferation,
      apoptosis, and invasion. The present study used immunohistochemistry analysis of
      S100A14 in clinical specimens of esophageal squamous cell carcinoma (ESCC) to
      show that decreased S100A14 is strongly correlated with poor differentiation.
      Furthermore, both mRNA and protein expression of S100A14 was drastically
      increased upon 12-O-tetra-decanoylphorbol-13-acetate (TPA) and calcium-induced
      esophageal cancer cell differentiation. Overexpression of S100A14 resulted in a
      G1-phase cell cycle arrest and promoted calcium-inhibited cell growth.
      Conversely, decreasing S100A14 expression significantly promoted G1-S transition
      and prevented the morphologic changes associated with calcium-induced cell
      differentiation. Molecular investigation demonstrated that S100A14 altered the
      calcium-induced expression of late markers of differentiation, with the most
      prominent effect on involucrin (IVL) and filaggrin (FLG). Finally, it was
      determined that S100A14 is transcriptionally regulated by JunB and that S100A14
      and JunB status significantly correlated in ESCC tissue. In summary, these data
      demonstrate that S100A14 is transcriptionally regulated by JunB and involved in
      ESCC cell differentiation. IMPLICATIONS: This study further differentiates the
      molecular mechanism controlling the development and progression of esophageal
      cancer.

PMID- 24107297
TI  - Pro-inflammatory cytokines can act as intracellular modulators of commensal
      bacterial virulence.
AB  - Interactions between commensal pathogens and hosts are critical for disease
      development but the underlying mechanisms for switching between the commensal and
      virulent states are unknown. We show that the human pathogen Neisseria
      meningitidis, the leading cause of pyogenic meningitis, can modulate gene
      expression via uptake of host pro-inflammatory cytokines leading to increased
      virulence. This uptake is mediated by type IV pili (Tfp) and reliant on the PilT
      ATPase activity. Two Tfp subunits, PilE and PilQ, are identified as the ligands
      for TNF-alpha and IL-8 in a glycan-dependent manner, and their deletion results
      in decreased virulence and increased survival in a mouse model. We propose a
      novel mechanism by which pathogens use the twitching motility mode of the Tfp
      machinery for sensing and importing host elicitors, aligning with the inflamed
      environment and switching to the virulent state.

PMID- 24107299
TI  - Cytotechnologist-attended on-site evaluation of adequacy for metastatic disease
      involving bone and soft tissue.
AB  - INTRODUCTION: Image-guided fine needle aspiration (FNA) of the musculoskeletal
      system is expensive to perform and repeat, so on-site evaluation of adequacy
      (OSEA) is increasingly used to ensure an optimal sample. Metastatic disease to
      the musculoskeletal system is not uncommon and often requires OSEA when sampled.
      At large academic centers, cytotechnologists have filled the increased demand for
      OSEA. However, the performance of cytotechnologists has not been compared with
      that of cytopathologists for OSEA in FNA of metastatic disease involving bone and
      soft tissue. METHODS: We retrospectively analyzed 10 years of data in which both
      cytotechnologists and cytopathologists performed OSEA for 1,995 FNAs of bone and
      soft tissue sites in which metastatic malignancy was suspected or found. We
      calculated adequacy and accuracy statistics in conjunction with other variables
      including imaging modality, biopsy site, accompanying core biopsy, tissue type,
      final diagnosis, and number of smears. RESULTS: A total of 1,995 aspirates of
      metastatic disease carcinoma, melanoma or lymphoma to bone or soft tissue had
      OSEA performed by cytotechnologists (681, 33.7%) or cytopathologists (1,314,
      66.3%). The adequacy downgrade rate was statistically equivalent (4.1 vs. 3.6%; p
      = 0.64). CONCLUSION: Cytotechnologists and cytopathologists perform with
      reasonable equivalence at OSEA of aspirates from metastatic carcinoma, melanoma
      or lymphoma involving bone or soft tissue.

PMID- 24107300
TI  - BMP4 is increased in the aortas of diabetic ApoE knockout mice and enhances
      uptake of oxidized low density lipoprotein into peritoneal macrophages.
AB  - BACKGROUND: BMP4, a member of the transforming growth factor-beta superfamily, is
      upregulated in the aortas of diabetic db/db mice. However, little is known about
      its role in diabetic atherosclerosis. Therefore, we examined the roles of BMP4 in
      the formation of diabetic atherosclerosis in apolipoprotein E knockout (ApoE KO)
      mice and in the uptake of oxidized low density lipoprotein (oxLDL) in peritoneal
      macrophages of wild-type mice. METHODS: To induce diabetes, ApoE KO mice were
      intraperitoneally injected with streptozotocin. Diabetic and non-diabetic ApoE KO
      mice were then fed a high-fat diet for 4 weeks. Next, to investigate a role of
      BMP4 in the peritoneal macrophages, we examined the uptake of oxLDL in BMP4
      treated macrophages. RESULTS: Diabetic ApoE KO mice showed accelerated
      progression of aortic plaques accompanied by increased luminal plaque area.
      Western blot analysis showed that BMP4 expression in the whole aorta was greatly
      increased in diabetic ApoE KO mice, than non-diabetic mice. Western blot analysis
      showed that the BMP4/SMAD1/5/8 signaling pathway was strongly activated in the
      aorta from diabetic ApoE KO mice, compared with control ApoE KO mice. Double
      immunofluorescence staining showed that BMP4 was expressed in MOMA2-labeled
      macrophage in the aortic lesions of ApoE KO mice. BMP4 significantly increased
      the uptake of oxLDL into peritoneal macrophages in vitro. CONCLUSION: We show
      that in the aorta of diabetic ApoE KO mice, BMP4 is increased and activates
      SMAD1/5/8. Our in vitro findings indicate that BMP4 enhances oxLDL uptake in
      mouse peritoneal macrophages, suggesting BMP4 may be involved in aortic plaque
      formation in diabetic ApoE KO mice. Targeting BMP4 may offer a new strategy for
      inhibition of plaque progression and stabilization of atherosclerotic lesions.

PMID- 24107298
TI  - Beyond ubiquitination: the atypical functions of Fbxo7 and other F-box proteins.
AB  - F-box proteins (FBPs) are substrate-recruiting subunits of Skp1-cullin1-FBP (SCF)
      type E3 ubiquitin ligases. To date, 69 FBPs have been identified in humans, but
      ubiquitinated substrates have only been identified for a few, with the majority
      of FBPs remaining 'orphans'. In recent years, a growing body of work has
      identified non-canonical, SCF-independent roles for about 12% of the human FBPs.
      These atypical FBPs affect processes as diverse as transcription, cell cycle
      regulation, mitochondrial dynamics and intracellular trafficking. Here, we
      provide a general review of FBPs, with a particular emphasis on these expanded
      functions. We review Fbxo7 as an exemplar of this special group as it has well
      defined roles in both SCF and non-SCF complexes. We review its function as a cell
      cycle regulator, via its ability to stabilize p27 protein and Cdk6 complexes, and
      as a proteasome regulator, owing to its high affinity binding to PI31. We also
      highlight recent advances in our understanding of Fbxo7 function in Parkinson's
      disease, where it functions in the regulation of mitophagy with PINK1 and Parkin.
      We postulate that a few extraordinary FBPs act as platforms that seamlessly segue
      their canonical and non-canonical functions to integrate different cellular
      pathways and link their regulation. 

PMID- 24107301
TI  - Informing HIV prevention efforts targeting Liberian youth: a study using the
      PLACE method in Liberia.
AB  - BACKGROUND: Preventing HIV infection among young people is a priority for the
      Liberian government. Data on the young people in Liberia are scarce but needed to
      guide HIV programming efforts. METHODS: We used the Priorities for Local AIDS
      Control Efforts (PLACE) method to gather information on risk behaviors that young
      people (ages 14 to 24) engage in or are exposed to that increase their
      vulnerability for HIV infection. Community informants identified 240 unique
      venues of which 150 were visited and verified by research staff. 89 of the 150
      venues comprised our sampling frame and 571 females and 548 males were
      interviewed in 50 venues using a behavioral survey. RESULTS: Ninety-one percent
      of females and 86% of males reported being sexually active. 56% of females and
      47% of males reported they initiated sexual activity before the age of 15. Among
      the sexually active females, 71% reported they had received money or a gift for
      sex and 56% of males reported they had given money or goods for sex. 20% of
      females and 6% males reported that their first sexual encounter was forced and
      15% of females and 6% of males reported they had been forced to have sex in the
      past year. Multiple partnerships were common among both sexes with 81% females
      and 76% males reporting one or more sex partners in the past four weeks. Less
      than 1% reported having experiences with injecting drugs and only 1% of males
      reporting have sex with men. While knowledge of HIV/AIDS was high, prevention
      behaviors including HIV testing and condom use were low. CONCLUSION: Youth
      focused HIV efforts in Liberia need to address transactional sex and multiple and
      concurrent partnerships. HIV prevention interventions should include efforts to
      meet the economic needs of youth.

PMID- 24107302
TI  - [Productive social activities in mothers of intellectually disabled children
      moderate the relationship between caregiver burden and self-rated health].
AB  - OBJECTIVES: Recently, the length of time for which intellectually disabled
      children receive homecare has increased; hence, the mothers caring for these
      intellectually disabled children at home are being exposed to increasingly heavy
      caregiver burden. Previous studies have reported that negative psychological
      states, including caregiver burden, influence self-rated health status; however,
      when elderly people engaged in productive social activities, they experienced
      heightened positive psychological states. Therefore, the objective of this study
      was to investigate whether mothers' participation in productive social activities
      influenced the relationship between caregiver burden and self-rated health
      status. METHOD: We performed a cross-sectional study using a questionnaire that
      included items on self-rated health, the modified Japanese version of the Zarit
      Caregiver Burden Interview, productive social activities, and various confounding
      variables. We sent the questionnaires to 270 mothers belonging to patient and
      family advocacy groups. We then compared the self-rated health and caregiver
      burden between a group of mothers involved in productive social activities and a
      group not involved in such activities. The relationships between self-rated
      health, caregiver burden, and productive social activities were analyzed using
      analysis of variance (ANOVA) and post-hoc testing. RESULTS: We obtained 120 valid
      responses. Mothers with greater burden had worse self-rated health than the other
      group (r=-0.305). According to the ANOVA results, the self-rated health of
      mothers involved in productive social activities did not significantly differ
      between caregiver burden groups (mild burden group: 3.4 vs. severe burden group:
      3.12; F=1.3, P=.253), whereas the self-rated health of mothers without productive
      social activities showed a significant difference between caregiver burden groups
      (mild burden group: 3.4 vs. severe burden group: 2.7; F=5.6, P=.017). CONCLUSION:
      Mothers with greater burden had worse self-rated health. However, in mothers who
      were engaged in productive social activities, self-rated health did not differ
      between the mild burden and severe burden groups. Therefore, productive social
      activities can favorably moderate the relationship between caregiver burden and
      self-rated health.

PMID- 24107303
TI  - [Measuring the effects of cancer screening on non-participants of the generation
      who works using a questionnaire].

PMID- 24107304
TI  - [Improvement in dental caries status in 3-year-olds following a 5-year community
      based oral health program in Chokai Town, Akita, Japan].

PMID- 24107306
TI  - Improving carrier injection in colloidal CdSe nanocrystals by embedding them in a
      pseudomorphic ZnSe/ZnMgSe quantum well structure.
AB  - The incorporation of colloidal nanocrystals in a high crystalline quality
      semiconductor matrix, the efficient carrier injection into the embedded
      nanocrystals and the fast optical response are key features for the fabrication
      of novel optoelectronic nanodevices based on colloidal nanostructures as active
      optical material. Using a novel growth approach, colloidal bare CdSe and core
      shell CdSe/ZnS nanocrystals were monolithically incorporated in pseudomorphic
      ZnSe/ZnMgSe quantum wells in order to control and enhance the carrier transfer
      into the nanocrystals. The photoluminescence for bare CdSe nanocrystals
      incorporated in ZnSe/ZnMgSe quantum well structures is substantially enhanced in
      comparison to nanocrystals sandwiched in ZnSe epilayers, which we attribute to
      increased carrier injection into the embedded nanocrystals via the quantum well,
      resembling the function of a wetting layer in Stranski-Krastanov-grown quantum
      dots. Core-shell CdSe/ZnS nanocrystals embedded in quantum well structures do not
      show considerable PL modifications because the ZnS shell prevents the efficient
      carrier migration between the nanocrystal and the matrix. Systematic
      investigations of structural and optical properties by high-resolution x-ray
      diffraction, temperature-dependent photoluminescence and time-resolved emission
      are presented. 

PMID- 24107305
TI  - [Home care and place of death for elderly people living in the remote islands of
      Japan. An examination on the presence of inpatient facilities].
AB  - OBJECTIVES: The purpose of this study was to clarify the actual status of end-of
      life care for elderly people living in the remote islands of Japan, and whether
      the presence of inpatient facilities was related to the place of death, so as to
      obtain suggestions for constructing a system of end-of-life care. METHODS: The
      survey targeted caregivers (85 people) who cared for elderly people (aged 65 and
      over), who had been legally certified for long-term care, and who had died
      between April 2009 and July 2011 in five islands of Japan. Islands were selected
      from a list of remote islands specified in the Remote Islands Development Act and
      related laws. Using a mixed method embedded design, we conducted semi-structured
      interviews using a questionnaire that assessed the place and cause of the elderly
      patient's death, age at death, gender, and whether the patient or family members
      had requested that the patient be allowed to die at home. RESULTS: The proportion
      of elderly people who died at home in the group living on remote islands with no
      inpatient facilities was 39.0% (16 of 41 people), compared with 18.2% (8 of 44
      people) living on islands with inpatient facilities. The difference was
      significant (P=0.029). Among the 24 elderly people who died at home, 6 died of
      cancer. Terminally ill cancer patients were released to die at home under three
      conditions: the caregivers could provide sufficient care, the visiting physician
      was present, and pain control was provided. It was also possible for elderly
      cancer patients to receive end-of-life care in remote islands that did not have
      inpatient facilities. In addition, among the elderly people who died at home in
      the remote islands, home care had been recommended by medical staff. CONCLUSION:
      It is important for professionals coordinating home care to understand the
      characteristics of diseases, perform early assessment of caregiver situations,
      and collaborate with medical staff.

PMID- 24107307
TI  - Put a tiger in your tank: the polyclad flatworm Maritigrella crozieri as a
      proposed model for evo-devo.
AB  - Polyclad flatworms are an early branching clade within the rhabditophoran
      Platyhelminthes. They provide an interesting system with which to explore the
      evolution of development within Platyhelminthes and amongst Spiralia
      (Lophotrochozoa). Unlike most other flatworms, polyclads undergo spiral cleavage
      (similar to that seen in some other spiralian taxa), they are the only free
      living flatworms where development via a larval stage occurs, and they are the
      only flatworms in which embryos can be reared outside of their protective egg
      case, enabling embryonic manipulations. Past work has focused on comparing early
      cleavage patterns and larval anatomy between polyclads and other spiralians. We
      have selected Maritigrella crozieri, the tiger flatworm, as a suitable polyclad
      species for developmental studies, because it is abundant and large in size
      compared to other species. These characteristics have facilitated the generation
      of a transcriptome from embryonic and larval material and are enabling us to
      develop methods for gene expression analysis and immunofluorescence techniques.
      Here we give an overview of M. crozieri and its development, we highlight the
      advantages and current limitations of this animal as a potential evo-devo model
      and discuss current lines of research. 

PMID- 24107308
TI  - The interaction between smoking and Epstein-Barr virus as multiple sclerosis risk
      factors may depend on age.
AB  - The multiple sclerosis (MS) risk factors smoking and remote Epstein-Barr virus
      (EBV) infection have been suggested to interact statistically, but the results
      are conflicting. In a prospective study on 192 MS cases and 384 matched controls,
      we analysed levels of cotinine as a marker of smoke exposure, and Epstein-Barr
      Nuclear Antigen-1 antibody reactivity. We assessed interaction on the additive
      and multiplicative scales, and estimated the effects of the risk factors across
      strata of each other. The results suggest that a negative interaction may be
      present in samples drawn at a young age, and a positive interaction among older
      subjects. 

PMID- 24107310
TI  - Initiating a pediatric spasticity program with multispecialty and multi
      institutional support: a preliminary report.
AB  - We describe the initiation and development of a comprehensive multidisciplinary
      and multi-institutional program for the evaluation and management of youth with
      spasticity. A descriptive step-by-step process of the administrative and
      organizational sequence of the development of the program is delineated. The
      Spasticity Clinic now meets regularly, and multiple diagnostic and treatment
      modalities are performed. This experience may assist those that wish to initiate
      a similar venue for youth with spasticity.

PMID- 24107309
TI  - Predictors and dynamics of postpartum relapses in women with multiple sclerosis.
AB  - BACKGROUND: Several studies have shown that pregnancy reduces multiple sclerosis
      (MS) relapses, which increase in the early postpartum period. Postpartum relapse
      risk has been predicted by pre-pregnancy disease activity in some studies.
      OBJECTIVE: To re-examine effect of pregnancy on relapses using the large
      international MSBase Registry, examining predictors of early postpartum relapse.
      METHODS: An observational case-control study was performed including pregnancies
      post-MS onset. Annualised relapse rate (ARR) and median Expanded Disability
      Status Scale (EDSS) scores were compared for the 24 months pre-conception,
      pregnancy and 24 months postpartum periods. Clustered logistic regression was
      used to investigate predictors of early postpartum relapses. RESULTS: The study
      included 893 pregnancies in 674 females with MS. ARR (standard error) pre
      pregnancy was 0.32 (0.02), which fell to 0.13 (0.03) in the third trimester and
      rose to 0.61 (0.06) in the first three months postpartum. Median EDSS remained
      unchanged. Pre-conception ARR and disease-modifying treatment (DMT) predicted
      early postpartum relapse in a multivariable model. CONCLUSION: Results confirm a
      favourable effect on relapses as pregnancy proceeds, and an early postpartum
      peak. Pre-conception DMT exposure and low ARR were independently protective
      against postpartum relapse. This novel finding could provide clinicians with a
      strategy to minimise postpartum relapse risk in women with MS planning pregnancy.

PMID- 24107311
TI  - Regulatory T cells in cutaneous lesions of patients with Paracoccidioidomycosis.
AB  - Paracoccidioidomycosis (PCM) is a systemic mycosis caused by the dimorphic fungus
      Paracoccidioides brasiliensis, with high incidence in Brazil and very significant
      in Latin America. The disease is clinically classified as acute, subacute or
      chronic where the primary lesion initiates in the lungs and can spread to other
      organs such as the skin and mucous membranes. The lesions are characterized by
      granulomatous formation, organized according to the type of pattern of host
      immune response. We demonstrated and quantified by immunohistochemistry the
      expression of Foxp3, CD25, TGF-beta and IL-10 in thirty cutaneous lesions with
      different presentation of granulomatous response. Cells expressing Foxp3 and CD25
      were increased in lesions with compact granulomas. The expression of TGF-beta and
      IL-10 was similar in all PCM lesions. As previous studies, our data suggest the
      correlation of Treg cells with the chronicity of the disease and the
      participation in suppressing mechanism as a possible source of IL-10. TGF-beta
      and IL-10, two important suppressor cytokines, are expressed in great amounts in
      the lesions but our results do not allow correlating with the differences in the
      granulomatous response. 

PMID- 24107312
TI  - The NOD2 receptor does not play a major role in the pathogenesis of Group B
      Streptococcus in mice.
AB  - Group B Streptococcus (GBS) capsular type III is an important agent of life
      threatening invasive infections. It has been previously shown that encapsulated
      GBS is easily internalized by dendritic cells (DCs) and this internalization has
      an impact on cytokine production. The intracellular receptors or pathways
      underlying this response are not well understood. In this work, we investigated
      the role of NOD2 in the pathogenesis of GBS using a mouse model of infection.
      NOD2(-/-) mice showed similar levels of survival and bacteremia than control
      mice. Interestingly, ex vivo analysis of total spleen cells from infected animals
      showed that the absence of NOD2 results in reduced production of inflammatory
      cytokines. However this abridged inflammatory response does not seem to improve
      mouse survival. In conclusion, we demonstrated that NOD2 is not a crucial
      receptor to fight GBS infection and only partially contributes to the
      inflammatory response. 

PMID- 24107313
TI  - Is switching from brand name to generic formulations of phenobarbital associated
      with loss of antiepileptic efficacy?: a pharmacokinetic study with two oral
      formulations (Luminal((r)) vet, Phenoleptil((r))) in dogs.
AB  - BACKGROUND: In human medicine, adverse outcomes associated with switching between
      bioequivalent brand name and generic antiepileptic drug products is a subject of
      concern among clinicians. In veterinary medicine, epilepsy in dogs is usually
      treated with phenobarbital, either with the standard brand name formulation
      Luminal((r)) or the veterinary products Luminal((r)) vet and the generic
      formulation Phenoleptil((r)). Luminal((r)) and Luminal((r)) vet are identical 100
      mg tablet formulations, while Phenoleptil((r)) is available in the form of 12.5
      and 50 mg tablets. Following approval of Phenoleptil((r)) for treatment of canine
      epilepsy, it was repeatedly reported by clinicians and dog owners that switching
      from Luminal((r)) (human tablets) to Phenoleptil((r)) in epileptic dogs, which
      were controlled by treatment with Luminal((r)), induced recurrence of seizures.
      In the present study, we compared bioavailability of phenobarbital after single
      dose administration of Luminal((r)) vet vs. Phenoleptil((r)) with a crossover
      design in 8 healthy Beagle dogs. Both drugs were administered at a dose of 100
      mg/dog, resulting in 8 mg/kg phenobarbital on average. RESULTS: Peak plasma
      concentrations (Cmax) following Luminal((r)) vet vs. Phenoleptil((r)) were about
      the same in most dogs (10.9 +/- 0.92 vs. 10.5 +/- 0.77 MUg/ml), and only one dog
      showed noticeable lower concentrations after Phenoleptil((r)) vs. Luminal((r))
      vet. Elimination half-life was about 50 h (50.3 +/- 3.1 vs. 52.9 +/- 2.8 h)
      without differences between the formulations. The relative bioavailability of the
      two products (Phenoleptil((r)) vs. Luminal((r)) vet.) was 0.98 +/- 0.031,
      indicating that both formulations resulted in about the same bioavailability.
      CONCLUSIONS: Overall, the two formulations did not differ significantly with
      respect to pharmacokinetic parameters when mean group parameters were compared.
      Thus, the reasons for the anecdotal reports, if true, that switching from the
      brand to the generic formulation of phenobarbital may lead to recurrence of
      seizures are obviously not related to a generally lower bioavailability of the
      generic formulation, although single dogs may exhibit lower plasma levels after
      the generic formulation that could be clinically meaningful.

PMID- 24107314
TI  - PCR to detect Mycobacterium tuberculosis in respiratory tract samples: evaluation
      of clinical data.
AB  - Tuberculosis (TB) remains as an important public health problem worldwide.
      Therefore, the rapid detection of M. tuberculosis is of primary importance to
      effectively reduce transmission in patients. The aims of this study were to
      evaluate two in-house molecular tests: nested PCR (nPCR) and real-time PCR
      (rtPCR) to detect M. tuberculosis complex directly from clinical samples. The
      results were compared to the culture results and to the culture results plus
      clinical data of patients. The rtPCR and nPCR presented high sensitivity (Se) and
      specificity (Sp) (rtPCR 97.6% and 91.5%, nPCR 85.7% and 92.7%, respectively)
      compared to culture. When the results of the molecular tests were compared to the
      culture plus clinical data the Se and Sp were 90.2% and 97.3% for rtPCR and 80.4%
      and 98.6% for the nPCR, respectively. The results demonstrated that molecular
      assays of M. tuberculosis can provide a sensitive and rapid diagnostic of TB, and
      when used in addition to the clinical data of TB patients will help to improve
      the Sp of the diagnosis of pulmonary TB.

PMID- 24107315
TI  - Glucocorticoid-induced TNF receptor family-related protein ligand regulates the
      migration of monocytes to the inflamed intestine.
AB  - Glucocorticoid-induced TNF receptor family-related protein (GITR) regulates the
      function of both T cells and antigen-presenting cells (APCs), while the function
      of GITR ligand (GITR-L) is largely unknown. Here we evaluate the role of GITR-L,
      whose expression is restricted to APCs, in the development of enterocolitis. On
      injecting naive CD4(+) T cells, GITR-L(-/-)Rag(-/-) mice develop a markedly
      milder colitis than Rag(-/-) mice, which correlates with a 50% reduction of
      Ly6C(+)CD11b(+)MHCII(+) macrophages in the lamina propria and mesenteric lymph
      nodes. The same result was observed in alphaCD40-induced acute colitis and during
      peritonitis, suggesting an altered monocyte migration. In line with these
      observations, the number of nondifferentiated monocytes was approximately 3-fold
      higher in the spleen of GITR-L(-/-)Rag(-/-) mice than in Rag(-/-) mice after
      alphaCD40 induction. Consistent with the dynamic change in the formation of an
      active angiotensin II type 1 receptor (AT1) dimer in GITR-L(-/-) splenic
      monocytes during intestinal inflammation, the migratory capability of splenic
      monocytes from GITR-L-deficient mice was impaired in an in vitro transwell
      migration assay. Conversely, alphaGITR-L reduces the number of splenic Ly6C(hi)
      monocytes, concomitantly with an increase in AT1 dimers. We conclude that GITR-L
      regulates the number of proinflammatory macrophages in sites of inflammation by
      controlling the egress of monocytes from the splenic reservoir.

PMID- 24107316
TI  - Pulmonary mycoses diagnosed using exfoliative cytology: infection or
      colonization?
AB  - OBJECTIVES: Flexible bronchoscopy with exfoliative cytology is an important tool
      for the diagnosis of pulmonary fungal infections. The question of colonization
      versus true fungal infection is of critical importance. STUDY DESIGN: A 5-year
      retrospective analysis of all cases of pulmonary fungal infection diagnosed using
      exfoliative cytology was performed. Clinical, radiological, bronchoscopy and
      histopathology findings were recorded. RESULTS: A total of 69 cases of mycoses
      were retrieved. The most common fungal organism identified was Aspergillus
      followed by Candida and Pneumocystis. Most cases of Aspergillus and Candida in
      cytological specimens presented as a pulmonary mass or endobronchial growth and
      were diagnosed as carcinomas in biopsy specimens, thus representing colonization.
      All cases of Pneumocystis with bilateral ground glass infiltrates and
      cryptococcosis with parenchymal mass lesion in radiology represented true
      infection. Histoplasma was identified in pleural fluid from a known case of lung
      carcinoma. CONCLUSION: Aspergillus and Candida species are the most common fungal
      organisms. Most of these represent colonization of malignant growths. However,
      true fungal infections may also present as mass lesions and may masquerade
      malignancy clinically. Fluid cytological examination is an important diagnostic
      modality for pulmonary mycoses; however, it is important to correlate results
      with clinical, bronchoscopy and biopsy findings for accurate diagnosis and
      appropriate management.

PMID- 24107318
TI  - Turf toe repair: a technical note.
AB  - Turf toe injury typically describes an injury to the metatarsosesamoid complex of
      the hallux generally caused by a hyperextension force to the great toe. This
      injury may be accompanied by pain, deformity, and decreased athletic performance.
      Operative treatment to repair the damaged tissue can be difficult, and we present
      a technique description that may help simplify the surgical reconstruction.

PMID- 24107317
TI  - STAT1/3 and ERK1/2 synergistically regulate cardiac fibrosis induced by high
      glucose.
AB  - BACKGROUND: Hyperglycaemia promotes the proliferation of cardiac fibroblasts
      (CFs) and collagen synthesis in CFs. However, the molecular mechanism underlying
      the effects of HG on proliferation and collagen synthesis of CF, is not
      completely understood. OBJECTIVES: The objectives of the present study were to
      determine whether the STAT proteins has a functional role in high glucose-induced
      proliferation of CFs and collagen synthesis in vitro and whether the STAT
      signaling pathway and MAPK signaling pathway have synergetical effects on high
      glucose-mediated cardiac fibroblasts proliferation and collagen synthesis.
      METHODS: Rat CFs were cultured in Dulbecco's modified Eagle's medium,
      supplemented with 5.5 or 25 mmol/L D-glucose, in the presence of absence of STAT1
      inhibitor Fludarabine, STAT3 inhibitor S31-201 and ERK1/2 inhibitor PD98059.
      Proliferation were measured by the 3-(4,5-dimethyl-2 thiazoyl)-2,5-diphenyl-2H
      tetrazolium bromide (MTT) assay, the production of Type I and III collagen was
      evaluated using real-time quantitative RT-PCR and ELISA, and the phosphorylation
      expression of STAT1 and STAT3 were analyzed by Western blot. RESULTS: High
      glucose treatment promoted the proliferation of cardiac fibroblasts and collagen
      types I and III synthesis. High glucose treatment induced STAT1 and STAT3
      phosphorylation in cardiac fibroblasts, the mode and level of STAT1 and STAT3
      phosphorylation were significantly different. Fludarabine and S31-201 could both
      inhibited high glucose stimulated proliferation of cardiac fibroblasts and
      collagen types I and III synthesis with different effects. Combination of
      Fludarabine and PD98059 or combination of S31-201 and PD98059 both exhibited
      stronger inhibitions on proliferation of cardiac fibroblasts and collagen types I
      synthesis, but the effects and functional modes are different. CONCLUSION: Both
      STAT1 and STAT3 mediate the proliferation of cardiac fibroblasts and collagen
      synthesis induced by high glucose. STAT1 and STAT3 both have synergetic effects
      with ERK1/2 on regulating proliferation of cardiac fibroblasts and collagen types
      I synthesis.

PMID- 24107319
TI  - Neurothekeoma of the toe.
AB  - Neurothekeomas are benign connective tissue tumors probably of nerve sheath
      origin. Making diagnosis is often difficult, because of many histological similar
      looking tumors. Immunostaining of S-100 protein is a helpful method for
      differentiation. We report a case of subungual neurothekeoma affecting the little
      toe, which is to our knowledge the first to be described in the literature. In
      spite of an incomplete excision of the tumor with tails reaching to the base of
      the specimen, no recurrence after 1-year follow-up was observed.

PMID- 24107320
TI  - Effect of reciprocating file motion on microcrack formation in root canals: an
      SEM study.
AB  - AIM: To compare dentinal microcrack formation whilst using Ni-Ti hand K-files,
      ProTaper hand and rotary files and the WaveOne reciprocating file. METHODOLOGY:
      One hundred and fifty mandibular first molars were selected. Thirty teeth were
      left unprepared and served as controls, and the remaining 120 teeth were divided
      into four groups. Ni-Ti hand K-files, ProTaper hand files, ProTaper rotary files
      and WaveOne Primary reciprocating files were used to prepare the mesial canals.
      Roots were then sectioned 3, 6 and 9 mm from the apex, and the cut surface was
      observed under scanning electron microscope (SEM) and checked for the presence of
      dentinal microcracks. RESULTS: The control and Ni-Ti hand K-files groups were not
      associated with microcracks. In roots prepared with ProTaper hand files, ProTaper
      rotary files and WaveOne Primary reciprocating files, dentinal microcracks were
      present. There was a significant difference between control/Ni-Ti hand K-files
      group and ProTaper hand files/ProTaper rotary files/WaveOne Primary reciprocating
      file group (P < 0.001) with ProTaper rotary files producing the most microcracks.
      No significant difference was observed between teeth prepared with ProTaper hand
      files and WaveOne Primary reciprocating files. CONCLUSION: ProTaper rotary files
      were associated with significantly more microcracks than ProTaper hand files and
      WaveOne Primary reciprocating files. Ni-Ti hand K-files did not produce
      microcracks at any levels inside the root canals.

PMID- 24107321
TI  - High frequency top-down junction-less silicon nanowire resonators.
AB  - We report here the first realization of top-down silicon nanowires (SiNW)
      transduced by both junction-less field-effect transistor (FET) and the
      piezoresistive (PZR) effect. The suspended SiNWs are among the smallest top-down
      SiNWs reported to date, featuring widths down to ~20 nm. This has been achieved
      thanks to a 200 mm-wafer-scale, VLSI process fully amenable to monolithic CMOS co
      integration. Thanks to the very small dimensions, the conductance of the silicon
      nanowire can be controlled by a nearby electrostatic gate. Both the junction-less
      FET and the previously demonstrated PZR transduction have been performed with the
      same SiNW. These self-transducing schemes have shown similar signal-to-background
      ratios, and the PZR transduction has exhibited a relatively higher output signal.
      Allan deviation (sigmaA) of the same SiNW has been measured with both schemes,
      and we obtain sigma(A) ~ 20 ppm for the FET detection and sigma(A) ~ 3 ppm for
      the PZR detection at room temperature and low pressure. Orders of magnitude
      improvements are expected from tighter electrostatic control via changes in
      geometry and doping level, as well as from CMOS integration. The compact, simple
      topology of these elementary SiNW resonators opens up new paths towards ultra
      dense arrays for gas and mass sensing, time keeping or logic switching systems on
      the SiNW-CMOS platform.

PMID- 24107322
TI  - Utilization of p40 (DeltaNp63) with p63 and cytokeratin 5/6 immunohistochemistry
      in non-small cell lung carcinoma fine-needle aspiration biopsy.
AB  - OBJECTIVE: Specific subclassification of pulmonary non-small cell carcinoma
      (NSCCA) is clinically necessary, and the aim of this study is to examine the
      utilization of p40 (DeltaNp63) in fine-needle aspiration (FNA) biopsy for lung
      NSCCA. STUDY DESIGN: Database files of the Washington University Medical Center
      were searched. Patients who underwent endobronchial ultrasound and CT FNA of a
      primary lung neoplasia were selected and immunohistochemistry (IHC) was
      performed. A panel of markers was utilized, including p40, p63, cytokeratin (CK)
      5/6, thyroid transcription factor, and napsin. RESULTS: One hundred patients were
      identified and comprised 38 squamous cell carcinomas (SCCA), 46 adenocarcinomas
      (AdCA), and 16 NSCCA. For SCCA, p40 was positive in 34/38 cases (89%) and
      negative in 4/38 cases (11%); p63 was positive in 33/38 cases (87%) and negative
      in 5/38 cases (13%); CK5/6 was positive in 38/38 cases. For AdCA cases, p40 was
      negative, p63 was positive in 2 cases (5%) and CK5/6 was negative in 43/46 cases
      (92%). CONCLUSION: For NSCCA, p40 had 89% sensitivity and 100% specificity
      compared to p63 with 86% sensitivity and 96% specificity and CK5/6 with 100%
      sensitivity and 96% specificity. In the evaluation of FNA biopsy for pulmonary
      NSCCA, p40 is a useful IHC marker for neoplastic subclassification, with better
      specificity in comparison to p63.

PMID- 24107323
TI  - Fruit and vegetable consumption revisited.

PMID- 24107324
TI  - Memantine in patients with moderate to severe Alzheimer's disease: meta-analyses
      using realistic definitions of response.
AB  - BACKGROUND/AIMS: We aimed to develop realistic definitions of clinical worsening
      in advanced Alzheimer's disease (AD) and to use them in a post hoc responder
      analysis of memantine. METHODS: 2,340 patients with moderate to severe AD (Mini
      Mental State Examination <20) were included from 9 multicentre, 16- to 28-week,
      randomised, double-blind, placebo-controlled studies of memantine 20 mg/day
      versus placebo. Responder meta-analyses were performed, with definitions of
      response based on minimally important differences (MIDs) on cognitive,
      functional, and global assessment scales. Validated or established MIDs were used
      where available; otherwise, MIDs were estimated by a data-driven approach, using
      data from our moderate to severe AD population. RESULTS: Patients with moderate
      to severe AD treated with memantine had a lower incidence of worsening from
      baseline to endpoint than patients treated with placebo, in cognition [24.4 vs.
      35.0%; odds ratio (OR) = 0.60; p < 0.001], function (38.1 vs. 43.4%; OR = 0.81; p
      = 0.01), global status (39.8 vs. 48.6%; OR = 0.70; p < 0.001), and in a combined
      'triple' worsening measure (9.4 vs. 16.1%; OR = 0.54; p < 0.001). CONCLUSIONS:
      New definitions of clinical worsening based on MIDs represent a more realistic
      functional decline in advanced stages of AD. Results of this new analysis show
      that memantine reduces the incidence of clinical worsening in key symptomatic
      domains in moderate to severe AD.

PMID- 24107325
TI  - Genetic variants and dilated cardiomyopathy. To be or not to be causative: is
      that the question?

PMID- 24107326
TI  - Mechanism of edge restenosis after drug-eluting stent implantation. Angulation at
      the edge and mechanical properties of the stent.
AB  - BACKGROUND: Edge restenosis is not an unusual finding after implantation of drug
      eluting stents (DES). We hypothesized that mechanical stress imposed on the stent
      edge would cause vessel wall injury and inflammation, which may consequently lead
      to edge restenosis. METHODS AND RESULTS: In total, 1,496 patients were implanted
      with a sirolimus-eluting stent (SES), paclitaxel-eluting stent (PES) or
      zotarolimus-eluting stent (ZES) in Seoul National University Hospital between
      2007 and 2009. Binary restenosis occurred in 161 lesions in 119 patients. We
      retrospectively compared the 3 DES with regard to the percentage of edge stent
      restenosis among all cases of restenosis. We also evaluated the maximal, minimal,
      and Delta (maximal angle-minimal angle) angles. The percentage of edge restenosis
      was higher for SES than for ZES (37.5% vs. 16.7%, P=0.017). Maximal angle at the
      proximal edge was 64.82 degrees +/-33.46 degrees  for 26 stents with proximal
      edge restenosis compared with 31.84 degrees +/-31.51 degrees  for 89 stents
      without proximal edge restenosis (P=0.001). The Delta angle was also
      significantly different between the 2 groups (14.81 degrees +/-15.98 degrees  vs.
      7.60 degrees +/-8.86 degrees , P=0.035). Similar findings were observed for
      distal edge restenosis. Both the maximal angle (39.09 degrees +/-21.04 degrees 
      vs. 22.71 degrees +/-22.83 degrees , P=0.010) and Delta angle (20.23 degrees +/
      15.39 degrees  vs. 9.18 degrees +/-9.66 degrees , P=0.016) at the distal edge
      were significantly different between the 2 groups. CONCLUSIONS: Physical stress
      determined by angulation at the stent edge segment and biomechanical properties
      of the DES can be considered as one of the plausible mechanisms for edge stent
      restenosis.

PMID- 24107327
TI  - European Society of Cardiology (ESC) congress report from Amsterdam 2013.
AB  - The Annual Congress of the European Society of Cardiology (ESC) was held in
      Amsterdam from the 31(st) of August to the 4(th) of September 2013. The total
      attendance up to the 3(rd) was 29,990. Several important topics were presented
      and discussed, including a randomized trial of preventive angioplasty in
      myocardial infarction (PRAMI), transcatheter aortic valve implantation, renal
      denervation, management of vasospastic angina, plaque vulnerability and outcome
      assessed by OCT and diuretic resistance in heart failure (an ESC-JCS [Japanese
      Circulation Society] joint session), and OCT-guided percutaneous coronary
      intervention. The ESC congress has become one of the most important and
      attractive international scientific meetings. Importantly, Japan topped the
      number of abstracts submitted (1,459 abstracts) and accepted (565 abstracts) to
      ESC 2013. Thus, the ESC is eager to continue the strong collaboration with the
      JCS as the relationship between them gets closer year by year.

PMID- 24107328
TI  - With respect to coefficient of linear thermal expansion, bacterial vegetative
      cells and spores resemble plastics and metals, respectively.
AB  - BACKGROUND: If a fixed stress is applied to the three-dimensional z-axis of a
      solid material, followed by heating, the amount of thermal expansion increases
      according to a fixed coefficient of thermal expansion. When expansion is plotted
      against temperature, the transition temperature at which the physical properties
      of the material change is at the apex of the curve. The composition of a
      microbial cell depends on the species and condition of the cell; consequently,
      the rate of thermal expansion and the transition temperature also depend on the
      species and condition of the cell. We have developed a method for measuring the
      coefficient of thermal expansion and the transition temperature of cells using a
      nano thermal analysis system in order to study the physical nature of the cells.
      RESULTS: The tendency was seen that among vegetative cells, the Gram-negative
      Escherichia coli and Pseudomonas aeruginosa have higher coefficients of linear
      expansion and lower transition temperatures than the Gram-positive Staphylococcus
      aureus and Bacillus subtilis. On the other hand, spores, which have low water
      content, overall showed lower coefficients of linear expansion and higher
      transition temperatures than vegetative cells. Comparing these trends to non
      microbial materials, vegetative cells showed phenomenon similar to plastics and
      spores showed behaviour similar to metals with regards to the coefficient of
      liner thermal expansion. CONCLUSIONS: We show that vegetative cells occur
      phenomenon of similar to plastics and spores to metals with regard to the
      coefficient of liner thermal expansion. Cells may be characterized by the
      coefficient of linear expansion as a physical index; the coefficient of linear
      expansion may also characterize cells structurally since it relates to volumetric
      changes, surface area changes, the degree of expansion of water contained within
      the cell, and the intensity of the internal stress on the cellular membrane. The
      coefficient of linear expansion holds promise as a new index for furthering the
      understanding of the characteristics of cells. It is likely to be a powerful tool
      for investigating changes in the rate of expansion and also in understanding the
      physical properties of cells.

PMID- 24107329
TI  - [History of occupational health physician and industrial safety and health law].
AB  - In Japan, an employer of a workplace with 50 or more employees is legally
      required to assign an occupational health physician. The assignment rate in 2010
      was reported as 87.0%. This policy started with the provision of "factory
      physician"in the Factory Law in 1938, then the Labour Standard Law stipulated
      "physician hygienist" in 1947, and finally the Industrial Safety and Health Law
      defined "occupational health physician" in 1972. In 1996, a revision of the law
      then required those physicians to complete training courses in occupational
      medicine, as designated by an ordinance. Historically, an on-site physician was
      expected to cure injuries and to prevent communicable diseases of factory
      workers. The means of occupational hygienic management by working environment
      measurements, etc., and of health management by health examinations, etc., were
      developed. Localized exhaust ventilation and personal protection equipment became
      widely utilized. Qualification systems for non-medical experts in occupational
      hygiene were structured, and relationships between employers and occupational
      health physicians were stipulated in the legislative documents. Currently, the
      Japan Medical Association and the University of Occupational and Environmental
      Health, Japan educate and train occupational health physicians, and the Japan
      Society for Occupational Health maintains a specialized board certification
      system for these physicians. In the future, additional efforts should be made to
      strengthen the expertise of occupational health physicians, to define and
      recognize the roles of non-medical experts in occupational hygiene, to
      incorporate occupational health services in small enterprises, to promote
      occupational health risk assessment in the workplace, and to reorganize the
      current legislation, amended repeatedly over the decades. 

PMID- 24107330
TI  - [Ethics and occupational physicians: ethics and mission required for occupational
      physicians].
AB  - The ethics of occupational physicians are considered from the following three
      viewpoints: (1) their legal standing and ethics in job execution; (2) ethics in
      research in occupational medicine; and (3) ethics in the 21st century and
      fundamental issues. We discuss: in (1), the contract types of occupational
      physicians and their independency and neutrality, the protection of health
      information and privacy, and the use of authority and the security measures; in
      (2), ethical standards of medical research in Japanese and international
      organizations, the significance and role of ethics committees, and issues
      characteristic of occupational health research; and in (3), occupational
      physicians and politic ethics, the practical abilities and ethics necessary for
      occupational physicians, and the practice and philosophy of occupational medicine
      as an art. These considerations suggest that occupational physicians, who have a
      special status based on the governmental policy of the occupational physician
      system, should develop an ethical consciousness at the core of their duties and
      perform their mission with responsibility to employees and employers, all of whom
      are Japanese citizens. Finally, we propose that the ultimate mission of
      occupational physicians is "to practice occupational medicine as a branch of the
      humanities." 

PMID- 24107331
TI  - [Current status and issues in development of occupational physicians in Japan].
AB  - Training systems for occupational physicians (OPs) have existed since the
      Industrial Safety and Health Act was enacted in 1972. However, it is necessary to
      enhance them because of changes in the business environment of Japanese
      corporations and working patterns have brought about new needs of occupational
      health (OH) activities. In this paper, OPs were classified into three categories;
      doctors who spend a part of working time on OH activities, i.e. "non-specialist
      OPs", doctors who engage in OH activities full-time, i.e. "specialists OPs", and
      doctors who manage corporate-wide occupational health programs or lead programs
      at OH service institutes, i.e. "lead OPs", and the status and the issues were
      reviewed. The major concern identified for each of the three categories in
      training were found to be quality management for non-specialist OPs, short supply
      for specialists OPs, and development of competencies such as leadership and
      management skills for lead OPs, respectively. Current efforts and ideas to
      improve the training systems were discussed. 

PMID- 24107332
TI  - [Certified occupational physician system of Japan Society for Occupational
      Health].
AB  - Certified Occupational Physician System (COPS) of Japan Society for Occupational
      Health has been in existence for 21 years, since 1992. UOEH has supported this
      system as a secretary general. In this report, we review the 2012 revision of
      COPS. With the new title of Certified Associate Occupational Physician (CAOP),
      this revision was established to produce well-educated and experienced
      occupational physicians. The title of COP is not competitive but independent to
      other titles such as occupational physician, medical advisor in industrial health
      or industrial health consultant. In addition, the aim of COPS is not the
      replacement to these existing systems. Furthermore, the COP should be active in
      industrial and occupational health, and should cooperate with existing systems
      through the sharing of experience and knowledge. 

PMID- 24107333
TI  - [University of Occupational and Environmental Health, Japan: 2013 alumni
      physician statistics].
AB  - The University of Occupational and Environmental Health, Japan (UOEH) is a
      publically funded medical school for occupational health physician and
      researchers. All students are funded through six years of medical school and
      commit to a nine-year health services of occupational medicine after graduation.
      Between 1984 and 2013, the number of physicians graduating from UOEH was 2,875.
      Of these, 473 were medical residents in our postgraduate residency programs and
      526 were occupational health physicians affiliated with different companies. A
      total of 252 graduates became UOEH research/teaching staff, 219 obtained
      employment as physicians at Rousai hospital (hospital operated by Japan Labour
      Health and Welfare Organization), and 84 entered industrial hygiene and health
      check organizations. UOEH alumni are distributed throughout Japan in large
      workplaces/ business establishments. Many physicians continued in their job after
      the nine-year obligation, thus contributing to the increasing number of
      occupational health physicians during recent decades. We suggest that funding and
      postgraduate residency programs contribute to the increasing numbers of
      physicians, but further analysis needs to be done. 

PMID- 24107334
TI  - [Current status of occupational health activities and the way that occupational
      health services should be offered to small- and medium-scale enterprises].
AB  - Activating occupational safety and health activities among Small- and Medium
      scale Enterprises (SMEs) is a major issue because more than 80% of Japanese
      workers belong to these enterprises, in which the number of workers are less than
      300 people. However, as the size of the enterprise decreases, the occurrence of
      problems of safety and health management systems and safety and health activities
      increases. Reasons for this include both the limitations of investments shortages
      of human resources. Occupational health services in SMEs has been provided by the
      cooperation of the following institutions: public associations (such as Regional
      Occupational Health Centers, Occupational Health Promotion Centers, Japan
      Industrial Safety and Health Association (JISHA)), occupational health agencies
      which provide checkup services, health insurance associations, and regional
      medical services. In contrast to the low coverage of occupational health services
      among SMEs in Japan, there are some countries in Europe in which this coverage is
      almost 100%. This is because of the development of occupational health services
      outside the company. To show the benefits of the safety and health activities to
      managers of SMEs, and to motivate them to take advantage of the services, it is
      important to consider measurements. Also, establishing systems that provide those
      services, improving the quality of specialists such as occupational physicians,
      and educating human resources, are all necessary. 

PMID- 24107335
TI  - [The role and future task of the occupational health nurse].
AB  - The Industrial Safety and Health Act was enacted focusing on occupational disease
      prevention in 1972. It has been revised over the years to include consideration
      of work associated diseases, and the participation and cooperation of employer
      and employees. From now, positive participation of employer-and-employees in
      occupational health activity becomes important in order to achieve the expanded
      purpose of the law. It is necessary to empower all workers to be able to perform
      occupational health activity independently. Florence Nightingale defined nursing
      in the 1850's. "Nursing is to put the patient in the best condition by
      improvement of environment, including a population approach. The goal of nursing
      is to enable the patient to use his faculty fully." The Public Health Nurse is,
      "assistance to the process of solving one's health, identifying health issues
      based on a community, using systematic measures which lead to prevention, and
      aiming at public responsibility." The daily activity of Nurses including
      Occupational Health Nurses (OHNs) is based on the theory and technology of
      "empowerment". In promoting the employer-and-employees independent Occupational
      Safety and Health Activity, the OHN's professional specialty of "empowerment" can
      play an important role. 

PMID- 24107336
TI  - [The occupational physician in France].
AB  - The French Labor law defines the role and its allocation criteria of the
      occupational physician (OP) the same as in Japan. In France, occupational
      medicine is one of the medical specialties. The OP resident must follow the 4
      years clinical training before certification. After having finished their
      residency, they are entitled to work for the occupational health service office
      of a company or company association (in the case of small and medium sized
      companies). The most important characteristics of the French system is that they
      cover all workers regardless of company size. The main role of the OP is
      prevention of work related diseases and accidents. They are not allowed to do
      clinical services except for emergency cases. Their main activities are health
      examinations, health education, patrol and advice for better working condition.
      Formerly, it was rather difficult to attract the medical students for OP resident
      course because of its prevention oriented characteristics. A growing concern
      about the importance of health management at the work site, however, has changed
      the situation. Now, the number of candidates for OP resident course is
      increasing. Their task has expanded to cover mental health and other life style
      related diseases. The 2011 modification of law redefines the role of the OP as a
      director of an occupational health service office who has a total responsibility
      of multidisciplinary services. The French and Japanese occupational health
      systems have many of similarities. A comparative study by researchers of UOEH is
      expected to yield useful information. 

PMID- 24107337
TI  - [Present state and problems of work environment control in the workplaces using
      hazardous materials based on the Occupational Safety and Health Act in Japan].
AB  - In Japan, working environment measurement is prescribed in the designated
      workplaces using hazardous materials. Measurements should be carried out
      periodically and countermeasures are performed depending on the results. By
      introducing such a system, working environments have remarkably improved.
      However, in the designated workplaces, measurements should be continued even in
      work environments found safe. On the other hand, measurement need not be obliged
      for non-designated workplaces even if hazardous materials are utilized.In the
      United States of America and many European countries, work environment management
      and work management are carried out by measuring personal exposure
      concentrations. In Japan, the Ministry of Health, Labour and Welfare is now
      discussing the introduction of personal exposure monitoring. However, many
      problems exist to prevent the simple introduction of American and European
      methods. This paper describes the brief history, present state and problems of
      work environment control in Japan, comparing with the systems of American and
      European countries. 

PMID- 24107338
TI  - [Working environmental control for industrial physicians].
AB  - Forty years has passed after the promulgation of the Industrial Safety and Health
      Law, Japan. In this paper, working environmental control based on the law was
      overviewed. The working environmental control includes evaluation and engineering
      controls of hazardous elements in the work environment. It is an important task
      for industrial physicians to conduct, similar to workers' health control. The
      annual cycle of evaluation and engineering control for environments is also
      similar to the cycle of diagnosis and clinical treatment for workers for the
      workers' health control. Historically, the working environmental control system
      was based on a list of worksites, using chemicals listed in the regulations, and
      the concentration of contaminants in the air at each work site. Recently, control
      banding of newly developed chemicals without administrative control levels, was
      introduced as a method for the working environmental control. 

PMID- 24107339
TI  - [Legislations on radiation in Japan].
AB  - The Atomic Energy Basic Act was the first law for the prevention of radiation
      damage in Japan, and was enforced in 1955. The law focused on the research,
      development and promotion of the use of atomic energy. With an increase in the
      importing of radioactive isotopes from foreign countries, the Act on Prevention
      of Radiation Disease Due to Radioisotopes was established under the jurisdiction
      of the Science and Technology Agency in 1957 and enforced in 1958. The Nuclear
      Regulation Authority began as an extra-ministerial committee of the Ministry of
      the Environment in 2012 and has jurisdiction in the area of ionizing radiations
      regulations.Substantial regulation has been provided by the Labor Standards Act,
      and the Ordinance on Prevention of Ionizing Radiation Hazards was established as
      the eleventh ordinance of the Ministry of Labor in 1959. There have been many
      revisions to the Ordinance, including revisions following the Fukushima Daiichi
      Nuclear Power Plant accident in 2011. This paper explains the Act on Prevention
      of Radiation Disease Due to Radioisotopes, the Ordinance on Prevention of
      Ionizing Radiation Hazards, and workmen's accident authorization. 

PMID- 24107340
TI  - [Toxicology of chemical substances (metals and organic solvents): management as
      an occupational physician].
AB  - Even in Japan, there was a time when cases of occupational poisoning had
      frequently occurred, which led to the enactment of the Industrial Safety and
      Health Act in 1972. Currently, the use of only a part of chemical substances
      utilized in the workplace is regulated according to their designated hazardous
      level, but there are many other substances whose toxicities have not been
      elucidated. Risk assessment is now required of entrepreneurs in all categories of
      industry by the recently-revised Industrial Safety and Health Act. This article
      will focus on the toxicology of metals and organic solvents, and it will discuss
      how occupational physicians should manage chemicals, including the ones whose
      toxicities have not been clarified. 

PMID- 24107341
TI  - [Biological monitoring and the occupational physician].
AB  - This article aims to introduce biological monitoring, which has been carried out
      in Japan for 25 years. Biological monitoring in occupational health is an
      assessment of the overall exposure to chemicals that are present in the workplace
      through measurement of the appropriate determinants in biological specimens in
      workers. Lead in blood and urinary delta-aminolevulinic acid in the urine of
      workers who handle lead, and urinary metabolites of workers who handle 8 kinds of
      organic solvents, are mandatory measurements. In 2013, insium and compounds,
      etheylbenzene (only coating workers), and cobalt and inorganic compounds were
      added to biological monitoring subjects, alongside the ordinal ones of specified
      chemical substances. Occupational physicians are required to carry out biological
      monitoring according to standardized protocols in order to correctly utilize
      biological monitoring results for occupational health management. 

PMID- 24107342
TI  - [Causes and prevention of occupational cancer].
AB  - Cancer is the leading cause of death in Japan, and is responsible for 30 % of all
      deaths. Among these deaths, the contributing rate of occupational cancer is only
      a few percent. However, it is a serious problem for workers exposed to certain
      carcinogens within the workplace, because they are subjected to high levels of
      carcinogens throughout their workday. The early adverse health effects exerted by
      carcinogens are closely related to carcinogenesis. As biomarkers for cancer
      prevention, 8-hydroxydeoxyguanosine, as an oxidative stress marker, DNA adducts,
      and cytosine C-5 methylation, as a marker of epigenetic change, may be useful to
      monitor. 

PMID- 24107343
TI  - [Pneumoconiosis law and occupational physician].
AB  - Pneumoconiosis law describes mainly the medical examination and its treatment for
      health care management. The revision of the medical examination and construction
      of the law has been performed according to the times. The main revised points are
      1) digital images such as CR and DR are accepted as a substitute of chest Xrays,
      2) the standard values in pulmonary function test are based on values of
      Japanese, and 3) bronchogenic carcinoma was recognized as a complication of
      pneumoconiosis. It is important to maintain occupational health management in
      order to avoid the onset of pneumoconiosis. Furthermore, an official notice from
      the ministry of health, labour and welfare established guidelines for the
      treatment of manufactured nanomaterials. It is important to actively maintain and
      update occupational health management to protect against materials of unknown
      harmful effects. 

PMID- 24107344
TI  - [Asbestos and the Industrial Safety and Health Law - in reference to the
      ordinance on prevention of hazards due to specified chemical substances and the
      ordinance on prevention of health impairment due to asbestos].
AB  - Recently in Japan, mesothelioma and lung cancer caused by asbestos are increasing
      in number and in proportion among occupational cancers. It is thus obvious that
      asbestos will remain an important theme in the field of occupational health and
      safety. We hereby report on the relationship between asbestos and the Industrial
      Safety and Health Law, the Ordinance on Prevention of Hazards due to Specified
      Chemical Substances, and the Ordinance on Prevention of Health Impairment due to
      Asbestos, in reference to laws and regulations as well as official notifications
      issued by the Ministry. In particular, we will focus on the process by which our
      country totally prohibited the use of asbestos, countermeasures to prevent
      exposure of workers, historical changes regarding administrative concentration
      levels, and measures for the management of health of workers handling and dealing
      with asbestos. 

PMID- 24107345
TI  - [The role of ergonomics in occupational health - past and future].
AB  - The aim of working condition and ergonomics is to control the task method and
      condition for the best productive activity with the highest efficiency and
      sustainability. The Principles of Scientific Management by Frederick Winslow
      Taylor and its criticism by Gito Teruoka, the 1st director of The Institute for
      Science of Labour, are introduced for a better understanding of work condition
      and ergonomics in this article. Occupational physician have a duty to control
      working method and condition to reduce the health hazards induced by job duty.
      Not only the technical knowledge of medicine, but also a fundamental knowledge of
      manufacturing is needed for the occupational physician. The development of tools
      for early detection of health hazards and workload evaluation, the introduction
      of work management systems with cooperation between occupational physicians and
      technical experts of manufacturing are needed for effective control of the
      workplace. The strengthening of the Industrial Safety and Health Law should help
      to drive these improvements. 

PMID- 24107346
TI  - [Countermeasures against secondhand smoke in occupational health in Japan].
AB  - Although Japan has been a signatory to the Framework Convention on Tobacco
      Control (FCTC) since 2004, progress in translating the recommendations into
      national policy has been limited, especially regarding the protection of non
      smokers from secondhand smoke (SHS).So far, it has been recommended to install
      designated smoking rooms in workplaces to prevent exposure to SHS in Japan. We
      examined the typical designated smoking room that was installed according to "The
      guidelines for smoking control in workplaces" introduced by the Ministry of
      Health, Labour and Welfare in 2003. It is revealed that such recommended smoking
      rooms are not functioning. It is necessary to implement smoke-free policy in
      order to prevent SHS in workplaces. 

PMID- 24107347
TI  - [Worksite health promotion and occupational physicians: interventional effects of
      exercises].
AB  - Results of annual health checkups at workplaces revealed a steady increase in the
      incidence of cardiovascular risk factors such as dyslipidemia and hypertension in
      Japan. With the aging of the workforce, the incidence is expected to increase
      further. These risk factors are modifiable through a lifestyle modification
      program including mild exercise and nutritional guidance. In 1988, the Japanese
      government revised the Industrial Safety and Health Law to promote health in the
      workplace and implemented the Total Health Promotion Plan (THP). However, only
      5.0% of workplaces were implementing THP programs according to a survey conducted
      in 2007. Therefore, we have recommended some measures for worksite health
      promotion, such as collaboration between community health and occupational health
      for implementing health promotion activities especially in small and medium scale
      enterprises, environmental improvement to promote occupational health, and an
      approach to increase physical activity that includes walking to work and using
      the stairs. Worksite health promotion should be considered an important company
      initiative in terms of work-related outcomes such as job satisfaction, work
      ability, and absenteeism in addition to cardiovascular risk factors. 

PMID- 24107348
TI  - [Role of occupational physician for workers' mental health].
AB  - In this paper, I briefly review the history of occupational mental health as well
      as administrative trends in Japan, and summarized how occupational physicians
      should get involved in these activities. As for mental health in the workplace,
      occupational physicians are required to participate in a large number of wide
      ranging activities, including the management of mental illness. On the other
      hand, approving the occupational physician who is in charge of mental health
      affairs only has some important ramifications which cannot be disregarded.
      Careful consideration should be given to this matter. 

PMID- 24107349
TI  - [Sleep problems in occupational health].
AB  - It is important for workers to maintain a high quality of sleep to obtain their
      best performance at the workplace and in daily life. Insufficient sleep and/or
      dyssynchrony between internal clock and external light/dark cycles cause daytime
      sleepiness, and could result in a reduction of the working efficiency. Sleepiness
      may sometimes cause enormous economic and social losses. A recent report also
      indicated that lack of sleep might be a risk factor for chronic health problems
      such as metabolic syndrome. Therefore, it is important for an occupational
      physician to investigate and understand the sleep problems in workers, both to
      prevent serious accidents or loss at the workplace and to keep workers in good
      health.Additionally, the proper treatment of workers with some common sleep
      disorders such as an obstructive sleep apnea syndrome, or a circadian rhythm
      sleep disorder, needs to be understood. Shift work type is important for both
      worker's health and work management. 

PMID- 24107350
TI  - [International comparison of the definition of night work - promoting health care
      of shift workers].
AB  - In order to manage occupational exposure, it is necessary to define exposure. In
      terms of administrative management however, shift work is difficult to define
      because there is a wide variance of working schedules which do not belong to
      ordinal day time work. Thus, many countries define night work, which is easier to
      define based on night working time for administrative management, rather than
      shift work. On the other hand, the term "night work" has not been so common in
      medical research compared to the term "shift work". Further, those two words were
      used in nearly same context among medical researchers in many cases. Given the
      current situation, for the purpose of promoting occupational health, it is
      reasonable to treat those two medical and administrative words as synonymous in
      order to make full use of medical evidence with linkage to the current
      administrative system. 

PMID- 24107351
TI  - [Healthcare for working women and occupational physician].
AB  - A low birthrate and aging society have led to a decrease in the Japanese work
      force. Therefore, maintaining the environment surrounding working women has
      become an important priority of the occupational physician. As for laws on
      women's healthcare, revision allows adaptation to fit changes in the times. In
      2012, a revision of the "Labour Standards for Women" included the addition of
      several harmful chemical substances and acceptable safety levels were established
      according to current toxicology study. In this report, we examine the effect on
      women's health of three laws; "Labour Standards Act", "Labour Standards for
      Women" and "Act on Securing, Etc. of Equal Opportunity and Treatment between Men
      and Women in Employment". Finally, the details of the 2012 revision of "Labour
      Standards for Women" are described. 

PMID- 24107352
TI  - [Health inequalities and occupational health].
AB  - There has been an emergent issue of health inequalities in Japan. Tackling health
      inequalities has been put on the primary agenda in the revised national health
      promotion campaign, so called "Kenko-Nippon-21"(Healthy Japan 21), which was
      announced in 2012. Against the background of this social movement, the present
      article argues how occupational health can contribute to health inequality issue
      based on the knowledge of public health and social epidemiology.Firstly, we
      reviewed a brief sketch of health inequality at occupational settings including
      position, job, and employment status. Secondly, we de scribed a conceptual model
      of a causal pathway of occupational class and health, based on the idea of life
      course approach, and models such as cumulative model, trigger model and latent
      effect/sensitive period model. Finally, we proposed that health impact assessment
      as a tool to mitigate health inequality related to occupational policy. 

PMID- 24107353
TI  - Adaptive evolution of bat dipeptidyl peptidase 4 (dpp4): implications for the
      origin and emergence of Middle East respiratory syndrome coronavirus.
AB  - BACKGROUND: The newly emerged Middle East respiratory syndrome coronavirus (MERS
      CoV) that first appeared in Saudi Arabia during the summer of 2012 has to date
      (20th September 2013) caused 58 human deaths. MERS-CoV utilizes the dipeptidyl
      peptidase 4 (DPP4) host cell receptor, and analysis of the long-term interaction
      between virus and receptor provides key information on the evolutionary events
      that lead to the viral emergence. FINDINGS: We show that bat DPP4 genes have been
      subject to significant adaptive evolution, suggestive of a long-term arms-race
      between bats and MERS related CoVs. In particular, we identify three positively
      selected residues in DPP4 that directly interact with the viral surface
      glycoprotein. CONCLUSIONS: Our study suggests that the evolutionary lineage
      leading to MERS-CoV may have circulated in bats for a substantial time period.

PMID- 24107354
TI  - Doctors' groups are criticised for endorsing pro-industry guidelines.

PMID- 24107355
TI  - Evolution of the sex chromosomes in salmonid fishes.
AB  - Most of the information on sex chromosomes in salmonid fishes is for species in
      the 3 genera of the subfamily Salmoninae found in North America: Salvelinus,
      Salmo and Oncorhynchus. All of the species are male heterogametic with XY sex
      determination. Morphologically distinguishable sex chromosomes are found only in
      Salvelinus namaycush,S. fontinalis and Oncorhynchus mykiss. Sex chromosomes have
      been identified in the other species using a combination of chromosome mapping
      and fluorescence in situ hybridization with probes containing sex-linked markers.
      Although all species share conserved linkage groups, the major sex-determining
      locus (SD) is found at the telomere of a different linkage group in almost every
      species, suggesting that the SD often transposes to a new location at the time of
      speciation. In a couple of species, intraspecific variation has been found in the
      chromosomal location of the SD. Recently, sdY has been identified as the major
      sex-determining gene in rainbow trout, and it maps to the sex linkage group in
      all of these species. BACs containing sdY have been isolated and sequenced in
      O.mykiss, and the genetic markers adjacent to sdY are not sex-linked in the other
      Oncorhynchus species, suggesting that the transposed region is very small.
      Possible explanations for the frequent occurrence of transposition of the SD are
      discussed.

PMID- 24107356
TI  - Histone deacetylase inhibitors increase microRNA-146a expression and enhance
      negative regulation of interleukin-1beta signaling in osteoarthritis fibroblast
      like synoviocytes.
AB  - OBJECTIVE: MiR-146a exerts negative control on inflammatory responses by
      suppressing cytokine-induced expression of interleukin-1 receptor-associated
      kinase-1 (IRAK1) and tumor necrosis factor receptor-associated factor 6 (TRAF6)
      by impairing NF-kappaB activity and inhibiting the expression of target genes.
      Recent study suggests that histone deacetylases (HDACs) are involved in the
      regulation of microRNA (miRNA) expression. Therefore, we determined whether HDAC
      inhibitors can increase miR-146a expression, thereby inhibiting interleukin-1beta
      (IL-1beta)-induced signaling in osteoarthritis fibroblast-like synoviocytes (OA
      FLS). METHOD: MiRNA expression was analyzed using real-time PCR. IL-1beta-induced
      downstream signals and cytokine expression were evaluated using Western blotting
      and ELISA. Transcription factors regulating promoter activation were identified
      using chromatin immunoprecipitation assays. RESULTS: IL-1beta treatment of OA-FLS
      induced a mild (1.7-fold) increase in miR-146a expression that was unable to
      appropriately downregulate IRAK1 and TRAF6 expression. HDAC inhibitors, SAHA
      (vorinostat), and LBH589 (panobinostat) significantly (6.1- and 5.4-fold)
      elevated miR-146a expression by increasing the binding of the transcription
      factor NF-kappaB to the miR-146a promoter, and negatively regulated IL-1beta
      induced IKK/IkappaB/p65 phosphorylation signaling and IL-6 secretion. The
      increase in miR-146a expression induced by the HDAC inhibitors was prevented by
      transfection of miR-146a inhibitor or HDAC1 (class I HDAC), HDAC4 (class IIa
      HDAC), and HDAC6 (class IIb HDAC) overexpression, suggesting that they were due
      to inhibition of HDAC activity. CONCLUSIONS: Our study demonstrated that HDAC
      inhibitor treatment in OA-FLS significantly increased miR-146a expression and
      mediated markedly negative regulation to inhibit IL-1beta-induced signaling and
      cytokine secretion. Our results indicate the potential rationale of anti
      inflammatory effects for HDAC inhibitors.

PMID- 24107357
TI  - Evaluation of the internal structure of normal and pathological Guinea pig
      cochleae using optical coherence tomography.
AB  - Optical coherence tomography (OCT) makes it possible to visualize the internal
      structures of several organs, such as the eye, in vivo. Although visualization of
      the internal structures of the inner ear has been used to try and identify
      certain pathological conditions, attempts have failed mainly due to the thick
      bony capsule surrounding this end organ. After decalcifying the bony wall of the
      cochlea with ethylenediamine tetraacetic acid, we could clearly visualize its
      internal structures by using OCT. We identified endolymphatic hydrops, strial
      atrophy and damage to the organ of Corti, evident as a distention of Reissner's
      membrane, thinning of the lateral wall and flattening of the organ of Corti,
      respectively. When specimens embedded in paraffin, sliced and stained with
      hematoxylin and eosin (HE) were examined under a light microscope, the OCT images
      of normal and pathological cochleae were virtually identical with those of the HE
      specimens, except that the HE specimens exhibited several artifacts unrecognized
      in OCT images, which were considered to be induced during the preparation
      process. Since OCT enables one to obtain arbitrary plane images by manipulating
      the slice axis of the specimens and avoids any misinterpretation due to artifacts
      induced during histological preparation, our technique would be useful for
      examining cochlear pathologies without or prior to histological evaluations.

PMID- 24107358
TI  - Knowledge translation strategies to improve the use of evidence in public health
      decision making in local government: intervention design and implementation plan.
AB  - BACKGROUND: Knowledge translation strategies are an approach to increase the use
      of evidence within policy and practice decision-making contexts. In clinical and
      health service contexts, knowledge translation strategies have focused on
      individual behavior change, however the multi-system context of public health
      requires a multi-level, multi-strategy approach. This paper describes the design
      of and implementation plan for a knowledge translation intervention for public
      health decision making in local government. METHODS: Four preliminary research
      studies contributed findings to the design of the intervention: a systematic
      review of knowledge translation intervention effectiveness research, a scoping
      study of knowledge translation perspectives and relevant theory literature, a
      survey of the local government public health workforce, and a study of the use of
      evidence-informed decision-making for public health in local government. A logic
      model was then developed to represent the putative pathways between intervention
      inputs, processes, and outcomes operating between individual-, organizational-,
      and system-level strategies. This formed the basis of the intervention plan.
      RESULTS: The systematic and scoping reviews identified that effective and
      promising strategies to increase access to research evidence require an
      integrated intervention of skill development, access to a knowledge broker,
      resources and tools for evidence-informed decision making, and networking for
      information sharing. Interviews and survey analysis suggested that the
      intervention needs to operate at individual and organizational levels, comprising
      workforce development, access to evidence, and regular contact with a knowledge
      broker to increase access to intervention evidence; develop skills in appraisal
      and integration of evidence; strengthen networks; and explore organizational
      factors to build organizational cultures receptive to embedding evidence in
      practice. The logic model incorporated these inputs and strategies with a set of
      outcomes to measure the intervention's effectiveness based on the theoretical
      frameworks, evaluation studies, and decision-maker experiences. CONCLUSION:
      Documenting the design of and implementation plan for this knowledge translation
      intervention provides a transparent, theoretical, and practical approach to a
      complex intervention. It provides significant insights into how practitioners
      might engage with evidence in public health decision making. While this
      intervention model was designed for the local government context, it is likely to
      be applicable and generalizable across sectors and settings. TRIAL REGISTRATION:
      Australia New Zealand Clinical Trials Register ACTRN12609000953235.

PMID- 24107359
TI  - Increased incidence of Campylobacter jejuni-associated Guillain-Barre syndromes
      in the Greater Paris area.
AB  - The role of Campylobacter jejuni as the triggering agent of Guillain-Barre
      syndrome (GBS) has not been reassessed since the end of the 1990s in France. We
      report that the number of C. jejuni-related GBS cases increased continuously
      between 1996 and 2007 in the Paris region (mean annual increment: 7%, P = 0.007).

PMID- 24107360
TI  - Association of tamoxifen use and reduced cardiovascular events among asian
      females with breast cancer.
AB  - BACKGROUND: Tamoxifen is used for breast cancer treatment and has been reported
      to be beneficial for the cardiovascular system, but it is unclear whether
      tamoxifen exhibits a favorable cardiovascular effect in Asian patients. METHODS
      AND RESULTS: From January, 1998 to December, 2006, a breast cancer cohort study
      was conducted using the Taiwan National Health Insurance database. Patients were
      divided according to whether tamoxifen was used. Study endpoints were occurrence
      of acute myocardial infarction (AMI), ischemic or hemorrhagic stroke and total
      cardiovascular events. A total of 3,690 female subjects were enrolled (mean age
      50.1+/-11.3), 2,056 of whom received tamoxifen and 1,634 did not. During a mean
      follow-up of 6.9 years, the tamoxifen group had a significantly lower incidence
      of AMI (0.15% vs. 0.67%, P=0.008), ischemic stroke (1.99% vs. 3.30%, P=0.008),
      hemorrhagic stroke (0.15% vs. 0.55%, P=0.029), and total cardiovascular events
      (2.24% vs. 4.16%, P<0.001) than the non-exposed group. After adjusting for
      comorbidities, tamoxifen was independently associated with a reduced risk of
      myocardial infarction (hazard ratio [HR] 0.22; 95% confidence interval [CI] 0.07
      0.70, ischemic stroke (HR 0.52; 95% CI 0.35-0.78), hemorrhagic stroke (HR 0.25;
      95% CI 0.07-0.92), and total cardiovascular events (HR 0.54; 95% CI 0.37-0.78).
      CONCLUSIONS: In Asian female breast cancer patients, tamoxifen use was associated
      with reduced risks of AMI, ischemic, hemorrhagic stroke and total cardiovascular
      events.

PMID- 24107361
TI  - Human cardiac stem cells with reduced notch signaling show enhanced therapeutic
      potential in a rat acute infarction model.
AB  - BACKGROUND: Because human cardiac stem cells (CSC) have regeneration potential in
      damaged cardiac tissue, there is increasing interest in using them in cell-based
      therapies for cardiac failure. However, culture conditions, by which CSCs are
      expanded while maintaining their therapeutic potential, have not been optimized.
      We hypothesized that the plating cell-density would affect proliferation
      activity, differentiation and therapeutic potential of CSCs through the Notch
      signaling pathway. METHODS AND RESULTS: Human CSCs were plated at 4 different
      densities. The population doubling time, C-KIT positivity, and dexamethasone
      induced multidifferentiation potential were examined in vitro. The therapeutic
      potential of CSCs was assessed by transplanting them into a rat acute myocardial
      infarction (AMI) model. The low plating density (340cells/cm(2)) maintained the
      multidifferentiation potential with greater proliferation activity and C-KIT
      positivity in vitro. On the other hand, the high plating density
      (5,500cells/cm(2)) induced autonomous differentiation into endothelial cells by
      activating Notch signaling in vitro. CSCs cultured at low or high density with
      Notch signal inhibitor showed significantly greater therapeutic potential in vivo
      compared with those cultured at high density. CONCLUSIONS: CSCs cultured with
      reduced Notch signaling showed better cardiomyogenic differentiation and
      therapeutic potentials in a rat AMI model. Thus, reducing Notch signaling is
      important when culturing CSCs for clinical applications.

PMID- 24107362
TI  - Clinical predictors of contrast-induced acute kidney injury in patients
      undergoing emergency versus elective percutaneous coronary intervention.
AB  - BACKGROUND: To evaluate the incidence and clinical predictors of contrast-induced
      acute kidney injury (CI-AKI) in patients with ST-segment elevation myocardial
      infarction (STEMI), unstable angina pectoris/non-STEMI (UAP/NSTEMI), and stable
      AP (SAP) undergoing percutaneous coronary intervention (PCI). METHODS AND
      RESULTS: We enrolled 1,954 patients (SAP, n=1,222; UAP/NSTEMI, n=277; STEMI,
      n=455) who underwent PCI. Patients were categorized according to contrast media
      volume/estimated glomerular filtration rate ratio (CV/eGFR low: <2.0, mid: 2.0
      2.9, high: >=3.0). CI-AKI was defined as an increase in serum creatinine of
      0.5mg/dl or 25% within 1 week from contrast-medium injection. The incidence of CI
      AKI was highest among the STEMI patients (SAP, 4.24%; UAP/NSTEMI, 10.7%; STEMI,
      16.1%, P<0.01). Significant predictors of CI-AKI were emergency PCI (odds ratio
      [OR] 3.70; 95% confidence interval [CI] 2.55-5.37; P<0.001), ejection fraction
      <40% (OR 2.04; 95% CI 1.24-3.36; P=0.005), and hemoglobin <10g/dl (OR 0.02; 95%
      CI 1.17-4.55; P=0.02) after multivariate logistic regression analysis. In the SAP
      group, a CV/eGFR ratio >=3.0 was a significant predictor of CI-AKI (P=0.048), but
      not in UAP/NSTEMI and STEMI patients. CONCLUSIONS: UAP/NSTEMI and STEMI patients
      undergoing emergency PCI were at high risk for CI-AKI regardless of CV/eGFR
      ratio. Minimizing the dose of contrast medium based on eGFR might be valuable in
      reducing the risk of CI-AKI in SAP patients.

PMID- 24107363
TI  - Advanced oxidation protein products induce inflammatory response in fibroblast
      like synoviocytes through NADPH oxidase -dependent activation of NF-kappaB.
AB  - BACKGROUND: Advanced oxidation protein products (AOPPs), a marker of oxidative
      stress, are prevalent in many kinds of disorders. Rheumatoid arthritis (RA),
      mainly resulting from the dysfunction of fibroblast-like synoviocytes (FLSs), is
      related to oxidative stress. Although the increased levels of AOPPs in RA
      patients were reported, the effect of AOPPs on FLSs function still remains
      unclear. Therefore, our study aims to investigate whether AOPPs have an effect on
      the inflammatory response of FLSs in vitro. METHODS: FLSs obtained from both
      knees of rats were treated with or without AOPPs-modified rat serum albumin
      (AOPPs-RSA) in vitro. The mRNA and protein expression of tumor necrosis factor
      (TNF)-alpha, interleukin(IL)-1beta, matrix metalloproteinases(MMP)-3, MMP-13 and
      vascular endothelial growth factor (VEGF) were measured by real-time quantitative
      polymerase chain reaction and enzyme-linked immunosorbent assay (ELISA),
      respectively. Reactive oxygen species (ROS) generation was detected by
      fluorescent microscope and fluorescence microplate reader. Immunoprecipitation,
      Co-Immunoprecipitation and western blot were performed to examine the activity of
      nicotinamide adenine dinucleotide phosphate (NADPH) oxidase and nuclear factor
      kappa B (NF-kappaB). RESULTS: Exposure of FLSs to AOPPs upregulated the mRNA and
      protein expression of TNF-alpha, IL-1beta, MMP-3, MMP-13 and VEGF in a
      concentration dependent manner. AOPPs treatment triggered ROS production in FLSs,
      which was significantly abolished by ROS scavenger N-acetyl-L-cysteine (NAC),
      superoxide dismutase (SOD), NADPH oxidase inhibitors diphenyleneiodonium (DPI)
      and apocynin. Challenged AOPPs induced phosphorylation of p47(phox), triggered an
      interaction between p47(phox), p22(phox) and gp91(phox), and significantly
      upregulated expression of NADPH oxidase subunits p47(phox), p22(phox) and
      gp91(phox). IkappaB degradation and nuclear translocation of NF-kappaB p65
      induced by AOPPs were significantly blocked by SOD, NAC, DPI and apocynin.
      CONCLUSIONS: These data indicate that AOPPs induce inflammatory response in FLSs
      is medicated through NADPH oxidase-dependent activation of NF-kappaB.

PMID- 24107364
TI  - Confrontation naming errors in Alzheimer's disease.
AB  - BACKGROUND/AIMS: Impairment in visual interpretation, semantic conception, or
      word retrieval may contribute to the naming errors identified in the Boston
      Naming Test (BNT). We investigated the possible cognitive mechanism of the naming
      difficulty in Alzheimer's disease (AD) by analyzing the error patterns presented
      in the BNT. METHODS: The Chinese version of the 30-item BNT (BNT-30) was
      performed on 115 normal control (NC) subjects and 104 mild-to-moderate AD
      patients. Accurate rates after semantic and phonemic cues were analyzed. The
      frequencies of 7 types of error patterns in the AD patients and the NC subjects
      were compared. RESULTS: The accurate rate after semantic cues was significantly
      lower in the AD than in the NC groups, but phonemic cues were more helpful than
      semantic cues to achieve accurate naming in both groups. The AD patients made
      more errors in all error patterns. Particularly, the frequency of nonresponse
      errors (n = 806) in the AD group significantly exceeded that in the NC group (n =
      382). However, the distribution of the error patterns did not differ between the
      two groups. CONCLUSION: Naming difficulties in AD might be attributed to
      progressive semantic knowledge degradation. The AD and the NC groups differ
      quantitatively but not qualitatively in the error patterns in confrontation
      naming.

PMID- 24107365
TI  - Evidence for the adaptive significance of secondary compounds in vertebrate
      dispersed fruits.
AB  - Abstract Although the primary function of fleshy fruits is to attract seed
      dispersers, many ripe fruits contain toxic secondary compounds. A number of
      hypotheses have been proposed to explain this evolutionary paradox, most of which
      describe the potential adaptive role that secondary compounds may play in seed
      dispersal. However, some authors have argued that fruit secondary compounds may
      be nonadaptive and instead explain their occurrence as a pleiotropic consequence
      of selection for defense of leaves and other tissues. We address these
      alternative evolutionary hypotheses through a comparative examination of iridoid
      glycosides in the leaves, unripe fruits, and ripe fruits of Lonicera * bella
      (Belle's bush honeysuckle), combined with an examination of fruit damage and
      removal in natural populations. We provide several lines of evidence that fruit
      secondary compounds cannot be explained solely as a consequence of foliar
      defense, including higher concentrations and more individual compounds in fruits
      compared to leaves and a negative relationship between iridoid glycoside
      concentration and fruit damage. However, we also show that the compositions and
      concentrations of secondary compounds in leaves and fruits are not entirely
      independent, emphasizing that selection in different plant parts is intrinsically
      linked. We conclude that the adaptive significance of chemical traits is best
      considered in a whole-plant context that includes fruit-frugivore interactions. 

PMID- 24107366
TI  - The spatial structure of antagonistic species affects coevolution in predictable
      ways.
AB  - A current challenge in evolutionary ecology is to assess how the spatial
      structure of interacting species shapes coevolution. Previous work on the
      geographic mosaic of coevolution has shown that coevolution depends on the
      spatial structure, the strength of selection, and gene flow across populations.
      We used spatial subgraphs and coevolutionary models to evaluate how spatial
      structure and the location of coevolutionary hotspots (sites in which reciprocal
      selection occurs) and coldspots (sites in which unidirectional selection occurs)
      contribute to the dynamics of coevolution and the maintenance of polymorphisms.
      Specifically, we developed a new approach based on the Laplacian matrices of
      spatial subgraphs to explore the tendency of interacting species to evolve toward
      stable polymorphisms. Despite the complex interplay between gene flow and the
      strength of reciprocal selection, simple rules drive coevolution in small groups
      of spatially structured interacting populations. Hotspot location and the spatial
      organization of coldspots are crucial for understanding patterns in the
      maintenance of polymorphisms. Moreover, the degree of spatial variation in the
      outcomes of the coevolutionary process can be predicted from the network pattern
      of gene flow among sites. Our work provides us with novel tools that can be used
      in the field or the laboratory to predict the effects of spatial structure on
      coevolutionary trajectories.

PMID- 24107367
TI  - Swarm intelligence: when uncertainty meets conflict.
AB  - Good decision making is important for the survival and fitness of stakeholders,
      but decisions usually involve uncertainty and conflict. We know surprisingly
      little about profitable decision-making strategies in conflict situations. On the
      one hand, sharing decisions with others can pool information and decrease
      uncertainty (swarm intelligence). On the other hand, sharing decisions can hand
      influence to individuals whose goals conflict. Thus, when should an animal share
      decisions with others? Using a theoretical model, we show that, contrary to
      intuition, decision sharing by animals with conflicting goals often increases
      individual gains as well as decision accuracy. Thus, conflict-far from hampering
      effective decision making-can improve decision outcomes for all stakeholders, as
      long as they share large-scale goals. In contrast, decisions shared by animals
      without conflict were often surprisingly poor. The underlying mechanism is that
      animals with conflicting goals are less correlated in individual choice errors.
      These results provide a strong argument in the interest of all stakeholders for
      not excluding other (e.g., minority) factions from collective decisions. The
      observed benefits of including diverse factions among the decision makers could
      also be relevant to human collective decision making.

PMID- 24107368
TI  - Metabolic rates can drive individual differences in information and insurance use
      under the risk of starvation.
AB  - Variation in how individuals invest in acquiring information (sampling) and in
      insuring themselves against potential negative consequences of uncertainty (e.g.,
      by storing energy reserves) has been suggested to underlie consistent individual
      differences in suites of behavioral traits. However, the key drivers of
      individual differences in information use remain poorly understood. We use
      dynamic programming to explore how existing variation in metabolic rates (MRs)
      affects the use of sampling and insurance under starvation risk. Our analysis
      reveals nonlinear effects of MRs on diurnal patterns of sampling and insurance.
      Individuals with low MRs accrue reserves quickly, because they invest in sampling
      and are able to exploit profitable options when they arise. Individuals with
      intermediate MRs initially lose reserves, because sampling, while optimal, is
      relatively expensive; however, they later build reserves due to efficient
      exploitation of alternative foraging options. Sampling rarely pays for
      individuals with the highest MRs, which show relatively constant levels of energy
      reserves throughout the foraging period. Thus, individual variation in MRs on the
      scale observed in natural populations can lead to important differences in
      investment in sampling and insurance and may underpin consistent individual
      differences in suites of other behavioral traits, including individual
      differences in behavioral responsiveness.

PMID- 24107369
TI  - Predictability as a personality trait: consistent differences in intraindividual
      behavioral variation.
AB  - Although animal behavior is generally repeatable, most behavioral variation
      apparently occurs within rather than across individuals. With the exception of
      very recent interest in individual behavioral plasticity (consistent differences
      in responsiveness), this within-individual variation has been largely ignored
      despite its importance in the study of proximate and ultimate questions about
      behavior. Here, we repeatedly scored the undisturbed activity of 30 adult male
      mosquitofish across multiple observation bouts spanning 132 days ([Formula: see
      text] observations per fish). We found that the behavior of some individuals was
      consistently more predictable in a given context than others. Repeatability for
      this "intraindividual variation" (IIV; [Formula: see text]) was evident after
      accounting for individual differences in activity trends across days, and
      activity responses due to fine-scale temperature variation (i.e., individual
      plasticity in response to both variables). To our knowledge, this is the first
      evidence that predictability of behavior is a repeatable characteristic of
      individual animals. We suggest that IIV represents an important axis of
      consistent behavioral variation that has previously not been formally considered.
      Finally, individual differences in predictability may similarly exist for labile
      morphological and physiological traits but have seemingly not been studied.

PMID- 24107370
TI  - Correlated evolution of allometry and sexual dimorphism across higher taxa.
AB  - Empirical evidence suggests that Rensch's rule of allometric scaling of male and
      female body size, which states that body size divergence is greater across males
      than across females of a clade, is not universal. In fact, quantitative genetic
      theory indicates that the sex under historically stronger directional selection
      will exhibit greater interspecific variance in size. Thus, the pattern of
      covariance between allometry of male and female body size and sexual size
      dimorphism (SSD) across related clades allows a test of this causal hypothesis
      for macroevolutionary trends in SSD. We compiled a data set of published body
      size estimates from the amphibians, a class with predominantly female-biased SSD,
      to examine variation in allometry and SSD among clades. Our results indicate that
      females become the more size-variant sex across species in a family as the
      magnitude of SSD in that family increases. This rejects Rensch's rule and
      implicates selection on females as a driver of both amphibian allometry and SSD.
      Further, when we combine our data into a single analysis of allometry for the
      class, we find a significant nonlinear allometric relationship between female
      body size and male body size. These data suggest that allometry changes
      significantly as a function of size. Our results illustrate that the relationship
      between female size and male size varies with both the degree of sexual
      dimorphism and the body size of a clade.

PMID- 24107371
TI  - Allee effect from parasite spill-back.
AB  - The exchange of native pathogens between wild and domesticated animals can lead
      to novel disease threats to wildlife. However, the dynamics of wild host-parasite
      systems exposed to a reservoir of domesticated hosts are not well understood. A
      simple mathematical model reveals that the spill-back of native parasites from
      domestic to wild hosts may cause a demographic Allee effect in the wild host
      population. A second model is tailored to the particulars of pink salmon
      (Oncorhynchus gorbuscha) and salmon lice (Lepeophtheirus salmonis), for which
      parasite spill-back is a conservation and fishery concern. In both models,
      parasite spill-back weakens the coupling of parasite and wild host abundance
      particularly at low host abundance-causing parasites per host to increase as a
      wild host population declines. These findings show that parasites shared across
      host populations have effects analogous to those of generalist predators and can
      similarly cause an unstable equilibrium in a focal host population that separates
      persistence and extirpation. Allee effects in wildlife arising from parasite
      spill-back are likely to be most pronounced in systems where the magnitude of
      transmission from domestic to wild host populations is high because of high
      parasite abundance in domestic hosts, prolonged sympatry of domestic and wild
      hosts, a high transmission coefficient for parasites, long-lived parasite larvae,
      and proximity of domesticated populations to wildlife migration corridors.

PMID- 24107372
TI  - Heritability of life span is largely sex limited in Drosophila.
AB  - Males and females differ with respect to life span and rate of aging in most
      animal species. Such sexual dimorphism can be associated with a complex genetic
      architecture, where only part of the genetic variation is shared between the
      sexes. However, the extent to which this is true for life span and aging is not
      known, because studies of life span have given contradictory results and aging
      has not been studied from this perspective. Here we investigate the additive
      genetic architecture of life span and aging in Drosophila melanogaster. We find
      substantial amounts of additive genetic variation for both traits, with more than
      three-quarters of this variation available for sex-specific evolutionary change.
      This result shows that the sexes have a profoundly different additive genetic
      basis for these traits, which has several implications. First, it translates into
      an, on average, three-times-higher heritability of life span within, compared to
      between, the sexes. Second, it implies that the sexes are relatively free to
      evolve with respect to these traits. And third, as life span and aging are traits
      that integrate over all genetic factors that contribute to mortal disease, it
      also implies that the genetics of heritable disease differs vastly between the
      sexes.

PMID- 24107373
TI  - Phenotypic integration in response to incubation environment adaptively
      influences habitat choice in a tropical lizard.
AB  - Phenotypic integration, in which a suite of traits change in a correlated or
      covarying response to shifts in environmental conditions, may enhance an
      organism's fitness. In skinks, rocky environments select for longer limbs and
      rapid running and climbing. We examined whether differences in nest temperature
      coincident with specific habitats caused phenotypically integrated effects on
      morphology, locomotor performance, and behavior in the skink Carlia longipes.
      Specifically, we determined whether microhabitat choices were integrated with
      adaptive morphology for each habitat. Using a split-clutch design, we incubated
      eggs at thermal regimes that mimicked the thermal environments of nests from two
      habitat types (forest = warm; rocky = cool). Hatchlings from cool incubation
      environments had longer limbs and greater running and climbing speeds, which are
      likely to be beneficial for rocky habitats. In addition, individuals from cool
      incubation environments selected rocky microhabitats more frequently than did
      hatchlings from warm incubation environments. We demonstrate phenotypic
      integration in response to nest temperature that affected morphology,
      performance, and ultimately habitat selection in a way that should increase
      hatchling fitness.

PMID- 24107374
TI  - A free-ranging, feral mare equus caballus affords similar maternal care to her
      genetic and adopted offspring.
AB  - Adoption of nongenetic offspring occurs in a variety of species but is rare in
      equids. We report a case of adoption by a free-ranging, feral mare Equus caballus
      and compare the maternal care received by her genetic offspring (born 1995) to
      that of her adopted offspring (born 1996) for the first 30 weeks of development.
      We compare five measures of care: (1) total time spent suckling, (2) mare
      aggression during suckling, (3) number of mare-terminated suckling bouts, (4)
      contact maintenance, and (5) mare-foal distance. For most behaviors, we detected
      no difference in the mare's treatment of the two foals; however, mare-foal
      distance was greater for the genetic offspring. We compare hypotheses regarding
      the reasons for adoption, offering postpartum physiological state as a potential
      driver.

PMID- 24107375
TI  - A novel mechanism for a survival advantage of vigilant individuals in groups.
AB  - In many animal species, vigilance is crucial for avoiding predation. In groups,
      however, nonvigilant individuals could benefit from the vigilance of others
      without any of the associated costs. In an evolutionary sense, such exploitation
      may be compensated if vigilant individuals have a survival advantage. The novelty
      in our model is that the probability to detect a predator is "distance
      dependent." We show that even if nonvigilant individuals benefit fully from
      information produced by vigilant individuals, vigilant individuals nevertheless
      enjoy a survival advantage. This happens because detection of predators is more
      likely when vigilant individuals happen to be targets of predation. We expect
      this distance-dependent mechanism to be compatible with previously reported
      mechanisms.

PMID- 24107376
TI  - Reserve size and fragmentation alter community assembly, diversity, and dynamics.
AB  - Researchers have disputed whether a single large habitat reserve will support
      more species than many small reserves. However, relatively little is known from a
      theoretical perspective about how reserve size affects competitive communities
      structured by spatial abiotic gradients. We investigate how reserve size affects
      theoretical communities whose assembly is governed by dispersal limitation,
      abiotic niche differentiation, and source-sink dynamics. Simulations were
      conducted with varying scales of dispersal across landscapes with variable
      environmental spatial autocorrelation. Landscapes were inhabited by simulated
      trees with seedling and adult stages. For a fixed total area in reserves, we
      found that small reserve systems increased the distance between environments
      dominated by different species, diminishing the effects of source-sink dynamics.
      As reserve size decreased, environmental limitations to community assembly became
      stronger, alpha species richness decreased, and gamma richness increased. When
      dispersal occurred across short distances, a large reserve strategy caused
      greater stochastic community variation, greater alpha richness, and lower gamma
      richness than in small reserve systems. We found that reserve size variation
      trades off between preserving different aspects of natural communities, including
      alpha diversity versus gamma diversity. Optimal reserve size will depend on the
      importance of source-sink dynamics and the value placed on different
      characteristics of natural communities. Anthropogenic changes to the size and
      separation of remnant habitats can have far-reaching effects on community
      structure and assembly.

PMID- 24107377
TI  - Interspecific dominance via vocal interactions mediates altitudinal zonation in
      neotropical singing mice.
AB  - Interspecific aggression between ecologically similar species may influence
      geographic limits by mediating competitive exclusion at the range edge.
      Advertisement signals that mediate competitive interactions within species may
      also provide social information that contributes to behavioral dominance and
      spatial segregation among species. We studied the mechanisms underlying
      altitudinal range limits in Neotropical singing mice (Scotinomys), a genus of
      muroid rodent in which males vocalize to repel rivals and attract mates. We first
      delineated replacement zones and described temperature regimes on three mountains
      in Costa Rica and Panama where Chiriqui singing mice (S. xerampelinus) abruptly
      replace Alston's singing mice (S. teguina). Next, we conducted interspecific
      behavioral trials and reciprocal removal experiments to examine if interspecific
      aggression mediated species replacement. Finally, we performed reciprocal
      playback experiments to investigate whether response to song matched competitive
      interactions. Behavioral trials and removal experiments suggest that S.
      xerampelinus is behaviorally dominant and excludes S. teguina from higher, cooler
      altitudes. Playback experiments indicate that subordinate S. teguina is silenced
      and repelled by heterospecific song, whereas S. xerampelinus responded to
      heterospecifics with approach and song rates comparable to responses to
      conspecifics. Thus, interspecific communication reflects underlying dominance and
      suggests that acoustic signaling contributes to altitudinal zonation of
      ecologically similar congeners. Our findings implicate the use of social
      information in structuring spatial distributions of animal communities across
      landscapes and provide insight into how large-scale patterns are generated by
      individual interactions.

PMID- 24107378
TI  - Ecology and sexual selection: evolution of wing pigmentation in calopterygid
      damselflies in relation to latitude, sexual dimorphism, and speciation.
AB  - Our knowledge about how the environment influences sexual selection regimes and
      how ecology and sexual selection interact is still limited. We performed an
      integrative study of wing pigmentation in calopterygid damselflies, combining
      phylogenetic comparative analyses, field observations and experiments. We
      investigated the evolutionary consequences of wing pigmentation for sexual
      dimorphism, speciation, and extinction and addressed the possible
      thermoregulatory benefits of pigmentation. First, we reconstructed ancestral
      states of male and female phenotypes and traced the evolutionary change of wing
      pigmentation. Clear wings are the ancestral state and that pigmentation
      dimorphism is derived, suggesting that sexual selection results in sexual
      dimorphism. We further demonstrate that pigmentation elevates speciation and
      extinction rates. We also document a significant biogeographic association with
      pigmented species primarily occupying northern temperate regions with cooler
      climates. Field observations and experiments on two temperate sympatric species
      suggest a link between pigmentation, thermoregulation, and sexual selection,
      although body temperature is also affected by other phenotypic traits such as
      body mass, microhabitat selection, and thermoregulatory behaviors. Taken
      together, our results suggest an important role for wing pigmentation in sexual
      selection in males and in speciation. Wing pigmentation might not increase
      ecological adaptation and species longevity, and its primary function is in
      sexual signaling and species recognition.

PMID- 24107379
TI  - Lung tumor promotion by chromium-containing welding particulate matter in a mouse
      model.
AB  - BACKGROUND: Epidemiology suggests that occupational exposure to welding
      particulate matter (PM) may increase lung cancer risk. However, animal studies
      are lacking to conclusively link welding with an increased risk. PM derived from
      stainless steel (SS) welding contains carcinogenic metals such as hexavalent
      chromium and nickel. We hypothesized that welding PM may act as a tumor promoter
      and increase lung tumor multiplicity in vivo. Therefore, the capacity of chromium
      containing gas metal arc (GMA)-SS welding PM to promote lung tumors was evaluated
      using a two-stage (initiation-promotion) model in lung tumor susceptible A/J
      mice. METHODS: Male mice (n = 28-30/group) were treated either with the initiator
      3-methylcholanthrene (MCA;10 MUg/g; IP) or vehicle (corn oil) followed by 5
      weekly pharyngeal aspirations of GMA-SS (340 or 680 MUg/exposure) or PBS. Lung
      tumors were enumerated at 30 weeks post-initiation. RESULTS: MCA initiation
      followed by GMA-SS welding PM exposure promoted tumor multiplicity in both the
      low (12.1 +/- 1.5 tumors/mouse) and high (14.0 +/- 1.8 tumors/mouse) exposure
      groups significantly above MCA/sham (4.77 +/- 0.7 tumors/mouse; p = 0.0001).
      Multiplicity was also highly significant (p < 0.004) across all individual lung
      regions of GMA-SS-exposed mice. No exposure effects were found in the corn oil
      groups at 30 weeks. Histopathology confirmed the gross findings and revealed
      increased inflammation and a greater number of malignant lesions in the
      MCA/welding PM-exposed groups. CONCLUSIONS: GMA-SS welding PM acts as a lung
      tumor promoter in vivo. Thus, this study provides animal evidence to support the
      epidemiological data that show welders have an increased lung cancer risk.

PMID- 24107380
TI  - Predictors of continued HIV-risk behaviors among drug users in methadone
      maintenance therapy program in China--a prospective study.
AB  - BACKGROUND: To examine the predictors of continued drug- and sex-related HIV-risk
      behaviors among drug users in methadone maintenance therapy (MMT) programs in
      China. METHODS: We followed a sample of 5,035 drug users enrolled for the first
      time in MMT programs at baseline, 6 months, and 12 months utilizing a
      longitudinal prospective study design. Drug users' HIV-risk behaviors, MMT
      characteristics, and drug use, were assessed at all three waves using a
      structured interview and HIV/HCV status was assessed at baseline and 12-month
      follow-up using biological specimens. RESULTS: The point prevalence of HIV was
      7.6% and 78.4% for HCV at baseline. Results of generalized linear mixed logistic
      regression models revealed that HIV-positive MMT clients were more likely to
      engage in drug injection (aOR = 1.70) and syringe sharing (aOR = 4.73). HCV
      positive clients were more likely to inject drugs (aOR = 2.58), share syringes
      (aOR = 1.97), and have multiple sexual partners (aOR = 1.47). Adherence to MMT
      was the most significant predictor of reduced HIV-risk behaviors. CONCLUSIONS:
      Our data confirmed the positive effects of MMT on HIV prevention and underscored
      the urgency for programs to reduce HIV risk in HIV- and HCV-positive clients.
      There is a pressing need to strengthen existing counseling services for HIV
      positive drug users to reduce their drug-related risk behaviors and to provide
      counseling for HCV-positive drug users. Further studies are needed to explore
      interventions to address high dropout rates and low adherence among MMT clients.

PMID- 24107382
TI  - Concern about falling in older women with a history of falls: associations with
      health, functional ability, physical activity and quality of life.
AB  - BACKGROUND: Fear of falling has been linked to activity restriction, functional
      decline, decreased quality of life and increased risk of falling. Factors that
      distinguish persons with a high concern about falling from those with low concern
      have not been systematically studied. OBJECTIVE: This study aimed to expose
      potential health-related, functional and psychosocial factors that correlate with
      fear of falling among independently living older women who had fallen in the past
      year. METHODS: Baseline data of 409 women aged 70-80 years recruited to a
      randomised falls prevention trial (DEX) (NCT00986466) were used. Participants
      were classified according to their level of concern about falling using the Falls
      Efficacy Scale International (FES-I). Multinomial logistic regression analyses
      were performed to explore associations between health-related variables,
      functional performance tests, amount of physical activity, quality of life and
      FES-I scores. RESULTS: 68% of the participants reported a moderate to high
      concern (FES-I >= 20) about falls. Multinomial logistic regression showed that
      highly concerned women were significantly more likely to have poorer health and
      quality of life and lower functional ability. Reported difficulties in
      instrumental activities of daily living, balance, outdoor mobility and poorer
      quality of life contributed independently to a greater concern about falling.
      CONCLUSIONS: Concern about falling was highly prevalent in our sample of
      community-living older women. In particular, poor perceived general health and
      mobility constraints contributed independently to the difference between high and
      low concern of falling. Knowledge of these associations may help in developing
      interventions to reduce fear of falling and activity avoidance in old age.

PMID- 24107381
TI  - Gene duplication and neofunctionalization: POLR3G and POLR3GL.
AB  - RNA polymerase III (Pol III) occurs in two versions, one containing the POLR3G
      subunit and the other the closely related POLR3GL subunit. It is not clear
      whether these two Pol III forms have the same function, in particular whether
      they recognize the same target genes. We show that the POLR3G and POLR3GL genes
      arose from a DNA-based gene duplication, probably in a common ancestor of
      vertebrates. POLR3G- as well as POLR3GL-containing Pol III are present in
      cultured cell lines and in normal mouse liver, although the relative amounts of
      the two forms vary, with the POLR3G-containing Pol III relatively more abundant
      in dividing cells. Genome-wide chromatin immunoprecipitations followed by high
      throughput sequencing (ChIP-seq) reveal that both forms of Pol III occupy the
      same target genes, in very constant proportions within one cell line, suggesting
      that the two forms of Pol III have a similar function with regard to specificity
      for target genes. In contrast, the POLR3G promoter--not the POLR3GL promoter-
      binds the transcription factor MYC, as do all other promoters of genes encoding
      Pol III subunits. Thus, the POLR3G/POLR3GL duplication did not lead to neo
      functionalization of the gene product (at least with regard to target gene
      specificity) but rather to neo-functionalization of the transcription units,
      which acquired different mechanisms of regulation, thus likely affording greater
      regulation potential to the cell.

PMID- 24107383
TI  - Fine needle aspiration cytology of benign salivary gland tumors with
      myoepithelial cell participation: an institutional experience of 575 cases.
AB  - OBJECTIVE: The aim of this study was to evaluate the diagnostic accuracy of fine
      needle aspiration (FNA) cytology of benign salivary gland tumors with
      myoepithelial cell participation, namely, pleomorphic adenoma, basal cell adenoma
      and myoepithelioma, at a single institution over a period of 10 years. STUDY
      DESIGN: This study was based on 575 cytologic and matching histological samples
      (534 pleomorphic adenomas, 26 basal cell adenomas and 15 myoepitheliomas).
      RESULTS: In most cases (393/534) of pleomorphic adenoma, a precise diagnosis was
      given. However, only 2 cases of basal cell adenoma and 1 case of myoepithelioma
      were diagnosed definitively. Descriptive diagnosis, instead of a definite
      diagnosis, was rendered in 16.9% of pleomorphic adenomas, 53.8% of basal cell
      adenomas and 40.0% of myoepitheliomas. Among all cases, the possibility of
      malignancy was raised in 5.2% of pleomorphic adenomas, 15.4% of basal cell
      adenomas and 20.0% of myoepitheliomas with a variable degree of suspicion.
      CONCLUSION: In some cases, the distinction between these three neoplasms remains
      difficult in that all exhibit some degree of myoepithelial participation.
      However, FNA showed a high diagnostic accuracy in diagnosing benign salivary
      tumors with myoepithelial differentiation, and triage into this category provides
      sufficient information for clinicians to make treatment decisions.

PMID- 24107384
TI  - Aircraft noise is linked to raised risk of cardiovascular disease.

PMID- 24107385
TI  - The journey towards lung protective respiratory support in preterm neonates.
AB  - The aim of this conceptual review is to provide the reader with a broad
      perspective on progress made in respiratory support of preterm infants over the
      past five decades. Landmark discoveries are described in their historical context
      and underlying theories of lung protection are discussed. The review finishes by
      integrating different approaches and perspectives into a state-of-the-art concept
      for lung-protective ventilation in this fragile patient population. Improvements
      in neonatal respiratory support in the 1970s and 1980s have contributed to
      dramatic improvements of mortality and morbidity rates among neonates with
      respiratory failure. Continuous positive airway pressure, antenatal
      corticosteroids and surfactant replacement therapy revolutionized the care of
      preterm infants. With the recognition that atelectrauma, volutrauma and oxygen
      toxicity are the main factors contributing to ventilator-induced lung injury,
      lung-protective strategies, including noninvasive respiratory support, tidal
      volume targeting during conventional mechanical ventilation and high frequency
      ventilation were developed in the 1990s. Given the fact that progress made in the
      last decade has only resulted in minor improvements in mortality and morbidity
      rates of neonates with respiratory failure, it seems unlikely that further
      refinements of current technologies will produce giant leaps forward in high
      resource countries. It appears that entirely new approaches would be required. In
      contrast, knowledge and technology transfer of basic respiratory support
      strategies (e.g. use of oxygen, simple systems to provide continuous positive
      airway pressure), could have an enormous impact on the prognosis of neonates with
      respiratory failure in low-resource countries.

PMID- 24107386
TI  - Lithium fails to enhance neurogenesis in subventricular zone and dentate
      subgranular zone after intracerebral hemorrhage in rats.
AB  - OBJECTIVE: Application of lithium induces neurogenesis in the damaged brain in
      the global cerebral ischemia rat model. In a previous study of rats subjected to
      intracerebral hemorrhage (ICH), we have found that lithium treatment improves
      functional recovery and reduces acute brain swelling. In this follow-up study, we
      investigate whether the known beneficial effect of lithium on functional recovery
      after ICH can be explained by neurorestorative effect. METHODS: Intracerebral
      hemorrhage was induced using infusion of collagenase into the striatum in adult
      rats. Rats were treated by intraperitoneal injection with lithium chloride (1, 2,
      or 4 mEq/kg/day) or saline for 2 weeks leading to and 2 weeks following ICH
      induction. From post-ICH days 4-14, 5-bromo-20-deoxyuridine (BrdU) was
      administered daily. At 2 weeks post-ICH, immunohistochemical staining was
      performed for BrdU and doublecortin (Dcx). RESULTS: The neurological scores for
      lithium-treated rats improved significantly at 2 weeks post-ICH compared to
      saline-treated rats. In the subgranular zone (SGZ) and lateral subventricular
      zone (SVZ), numbers of BrdU-positive cells were not significantly different
      between the saline-treated and pooled lithium-treated groups. No significant
      differences in numbers of BrdU-positive cells in the SVZ were detected between
      the saline-treated and any of the lithium-treated groups. No significant
      differences in numbers of BrdU-positive cells in the SGZ were detected between
      the saline-treated and 1 mEq/kg lithium-treated group. Rats treated with ? 2
      mEq/kg lithium had lower numbers of BrdU-positive cells in the SGZ than did rats
      treated with saline, although this difference was not statistically significant.
      Numbers of Dcx-positive cells in the medial striatum were not significantly
      different between the 1 mEq/kg lithium-treated and saline-treated groups.
      CONCLUSION: The present study shows that lithium does not enhance neurogenesis
      after ICH in rats, and high dose lithium suppresses neurogenesis in the SGZ.
      Functional recovery after ICH may be attributable to neuroprotective effect, not
      neuroregenerative effect of lithium.

PMID- 24107387
TI  - Risk factors for nephrotoxicity in patients receiving outpatient continuous
      infusions of vancomycin in an Australian tertiary hospital.
AB  - OBJECTIVES: To assess the risk factors for nephrotoxicity caused by vancomycin
      continuous infusion in a predominantly Caucasian outpatient population. METHODS:
      This was a retrospective cohort study of 155 patient episodes from December 2006
      to December 2011. RESULTS: Vancomycin-associated nephrotoxicity (VN) occurred in
      26 of 155 (17%) patient episodes. After adjustment for baseline renal function,
      maximum steady-state vancomycin concentrations >=32 mg/L [OR 8.7 (95% CI 3.1
      29.6), P < 0.001] and angiotensin receptor blockade [OR 9.78 (95% CI 3.1-39.4), P
      < 0.001] were independently associated with VN. The cumulative dose and duration
      of vancomycin therapy were not independent predictors of VN. CONCLUSIONS:
      Cessation of angiotensin receptor-blocking medications in selected patient
      groups, enhanced monitoring and establishing target steady-state concentrations
      <30 mg/L to avoid excessive vancomycin exposure may reduce the risk of VN.

PMID- 24107388
TI  - Clinical and bacteriological effects of pivmecillinam for ESBL-producing
      Escherichia coli or Klebsiella pneumoniae in urinary tract infections.
AB  - OBJECTIVES: The prevalence of urinary tract infections (UTIs) caused by extended
      spectrum beta-lactamase (ESBL)-producing Enterobacteriaceae is increasing and the
      therapeutic options are limited, especially in primary care. Recent indications
      have suggested pivmecillinam to be a suitable option. Here, we evaluated the
      clinical and bacteriological effects of pivmecillinam in UTIs caused by ESBL
      producing Enterobacteriaceae. METHODS: We carried out a prospective follow-up of
      39 patients diagnosed with UTI caused by ESBL-producing Enterobacteriaceae,
      initiated on pivmecillinam. The patients were from general practice (n = 29) or
      admitted to hospitals (n = 10) in the Copenhagen area, Denmark (n = 30) or
      Halland, Sweden (n = 9). Both patients and physicians were asked to complete a
      questionnaire on the pretreatment signs and symptoms. Patients were asked to send
      in two more urine samples for culture examination, together with questionnaires
      for clinical effect, 2-6 and 10-20 days, respectively, after end of treatment.
      RESULTS: Of the 39 patients included, 30 received a treatment regimen of 400 mg
      of pivmecillinam three times a day and 9 received 200 mg three times a day. All
      isolates were susceptible to mecillinam. The bacteriological cure rate was 79%
      (31/39); 80% (24/30) and 78% (7/9) for 400 and 200 mg three times a day,
      respectively. Relapse, i.e. ESBL-producing bacteria in the second control urine
      after previous bacteriological cure, was seen in five patients. Clinical cure was
      evaluable in 19 patients; 16 had a clinical effect (84%). CONCLUSIONS:
      Pivmecillinam was proven bacteriologically and clinically effective for treatment
      of lower UTIs caused by ESBL-producing Enterobacteriaceae.

PMID- 24107390
TI  - Low-temperature self-assembled vertically aligned carbon nanofibers as counter
      electrode material for dye-sensitized solar cells.
AB  - Low-temperature AC-DC PECVD is employed for direct growth of vertically aligned
      carbon nanofibers (VACNFs) on ordinary transparent conductive glass as counter
      electrode material for dye-sensitized solar cells (DSSCs). To the best of our
      knowledge, this is the first report on utilization of VACNFs grown directly on
      ordinary FTO-coated glass as a cost-effective catalyst material in DSSCs.
      According to the FESEM images, the as-grown arrays are well aligned and dense,
      and offer uniform coverage on the surface of the substrate. In-plane and out-of
      plane conductivity measurements reveal their good electrical conductivity, and
      Raman spectroscopy suggests a high number of electrocatalytic active sites,
      favoring charge transport at the electrolyte/electrode interface. Hybrid VACNF/Pt
      electrodes are also fabricated for performance comparison with Pt and VACNF
      electrodes. X-ray diffraction results verify the crystallization of Pt in hybrid
      electrodes and further confirm the vertical alignment of carbon nanofibers.
      Electrochemical characterization indicates that VACNFs provide both high
      catalytic and good charge transfer capability, which can be attributed to their
      high surface area, defect-rich and one-dimensional structure, vertical alignment
      and low contact resistance. As a result, VACNF cells can achieve a comparable
      performance (~5.6%) to that of the reference Pt cells (~6.5%). Moreover, by
      combination of the excellent charge transport and catalytic ability of VACNFs and
      the high conductivity of Pt nanoparticles, hybrid VACNF/Pt cells can deliver a
      performance superior to that of the Pt cells (~7.2%), despite having a much
      smaller amount of Pt loading, which raises hopes for low-cost large-scale
      production of DSSCs in the future.

PMID- 24107389
TI  - Emergence of resistance to daptomycin in a cohort of patients with methicillin
      resistant Staphylococcus aureus persistent bacteraemia treated with daptomycin.

PMID- 24107392
TI  - Validity and reliability of nutrition screening administered by nurses.
AB  - BACKGROUND: Nutrition screening is usually administered by nurses. However, most
      studies on nutrition screening tools have not used nurses to validate the tools.
      The 3-Minute Nutrition Screening (3-MinNS) assesses weight loss, dietary intake,
      and muscle wastage, with the composite score of each used to determine risk of
      malnutrition. The aim of the study was to determine the validity and reliability
      of 3-MinNS administered by nurses, who are the intended assessors. METHODS: In
      this cross-sectional study, 3 ward-based nurses screened 121 patients aged 21
      years and over using 3-MinNS in 3 wards within 24 hours of admission. A dietitian
      then assessed patients' nutrition status using Subjective Global Assessment
      within 48 hours of admission, while blinded to the results of the screening. To
      assess the reliability of 3-MinNS, 37 patients screened by the first nurse were
      rescreened by a second nurse within 24 hours, who was blinded to the results of
      the first nurse. The sensitivity, specificity, and best cutoff score for 3-MinNS
      were determined using the receiver operator characteristics curve. RESULTS: The
      best cutoff score to identify all patients at risk of malnutrition using 3-MinNS
      was 3, with sensitivity of 89% and specificity of 88%. This cutoff point also
      identified all (100%) severely malnourished patients. There was strong
      correlation between 3-MinNS and SGA (r = .78, P < .001). The agreement between 2
      nurses conducting the 3-MinNS tool was 78.3%. CONCLUSION: The 3-MinNS is a valid
      and reliable tool for nurses to identify patients at risk of malnutrition.

PMID- 24107391
TI  - Risks and benefits of prophylactic cyclic parenteral nutrition in surgical
      neonates.
AB  - BACKGROUND: Cyclic parenteral nutrition (PN) is used for both the treatment and
      prevention of parenteral nutrition-associated liver disease (PNALD). Early
      initiation of prophylactic cyclic PN may not be well tolerated in young neonates.
      Our objective was to test the hypothesis that prophylactic cyclic PN initiated
      prior to the onset of hyperbilirubinemia is associated with younger age at
      initiation, lower bilirubin levels, and similar rates of adverse events compared
      to therapeutic cyclic PN initiated after established cholestasis in surgical
      neonates. METHODS: A retrospective review of infants with gastrointestinal
      disorders requiring surgical intervention who received cyclic PN 2006-2011 was
      performed. RESULTS: Of the 43 infants eligible for analysis, 23 received
      prophylactic and 20 received therapeutic cyclic PN. Infants in both groups were
      comparable in demographics, surgical diagnoses, and illness severity. At
      initiation of cyclic PN, infants with prophylactic cyclic PN were significantly
      younger in chronologic (P = .003) and postmenstrual age (P = .029). Prophylactic
      cyclic PN was associated with a significantly lower incidence of
      hyperbilirubinemia (P = .001), lower maximum conjugated bilirubin (P < .0001),
      and lower last checked conjugated bilirubin (P = .032) compared to the
      therapeutic cyclic PN. The incidence of hypoglycemia, hyperglycemia, and
      hypertriglyceridemia was similar for the 2 groups. CONCLUSIONS: There may be a
      potential benefit to initiating cyclic PN prior to the development of
      hyperbilirubinemia in surgical neonates. Early initiation of prophylactic cyclic
      PN does not appear to increase the risk for adverse events.

PMID- 24107393
TI  - Guidance on preparing an investigational new drug application for fecal
      microbiota transplantation studies.
AB  - Fecal microbiota transplantation (FMT) is an effective treatment for Clostridium
      difficile infections that are refractory to antibiotic therapy. Because of the
      important roles of the microbiota in the function of the gastrointestinal tract
      and other aspects of human physiology, there is a growing interest in studying
      FMT for other clinical indications. The US Food and Drug Administration regulates
      clinical studies to evaluate the safety and efficacy of FMT. Studies of FMT for
      recurrent Clostridium difficile infection or other indications could require
      submission of an investigational new drug application. Most academic physicians
      and investigators do not have the regulatory experience necessary to undertake
      this process. We provide guidance to researchers on the preparation and
      submission of investigational new drug applications to study FMT. 

PMID- 24107394
TI  - Diet and inflammatory bowel disease: review of patient-targeted recommendations.
AB  - Patients have strong beliefs about the role of diet in the cause of inflammatory
      bowel disease (IBD) and in exacerbating or alleviating ongoing symptoms from IBD.
      The rapid increase in the incidence and prevalence of IBD in recent decades
      strongly suggests an environmental trigger for IBD, one of which may be dietary
      patterns. There are several pathways where diet may influence intestinal
      inflammation, such as direct dietary antigens, altering the gut microbiome, and
      affecting gastrointestinal permeability. However, data that altering diet can
      change the natural history of IBD are scarce, and evidence-based dietary
      guidelines for patients with IBD are lacking. Patients, therefore, seek
      nonmedical resources for dietary guidance, such as patient support groups and
      unverified sources on the Internet. The aim of this review is to identify patient
      targeted dietary recommendations for IBD and to critically appraise the
      nutritional value of these recommendations. We review patient-targeted dietary
      information for IBD from structured Internet searches and popular defined diets.
      Patient-targeted dietary recommendations focus on food restrictions and are
      highly conflicting. High-quality dietary intervention studies are needed to
      facilitate creation of evidence-based dietary guidelines for patients with IBD. 

PMID- 24107396
TI  - Screening of gastric cancer: who, when, and how.
AB  - Gastric cancer (GC) remains the leading cause of cancer mortality worldwide.
      Conceivably, early diagnosis may be achievable through screening of the high-risk
      population. Therefore, it is important to identify individuals harboring
      premalignant lesions that include atrophic gastritis, intestinal metaplasia, and
      mucosal dysplasia. The age threshold for GC screening depends on the regional
      incidence and the individual risk. In high-incidence countries such as Japan and
      Korea, the age to screen GC may be as early as 40 years. The mass screening by
      endoscopy in these countries would be able to detect a substantial portion of
      patients with early GCs as well as precancerous lesions. For the purpose of
      eliminating GC, however, these screening programs should be conducted in
      conjunction with Helicobacter pylori eradication. In low-incidence countries, it
      seems feasible to adopt a stepwise approach to identify high-risk individuals at
      first. The initial screening should focus on epidemiologic factors, genetic or
      hereditary risks, and the status of H pylori infection. Measurement of serum
      pepsinogen I and II and gastrin may detect atrophic gastritis in a noninvasive
      manner. Patients with these premalignant lesions should then receive endoscopic
      examination and enter surveillance. To date, there is no cost-effective strategy
      for an average-risk individual from a population with low incidence of GC, and
      therefore screening is unwarranted and cannot be recommended for them. 

PMID- 24107397
TI  - T3 translational science in gastroenterology: getting to best outcomes.
AB  - Achieving the best possible outcomes requires the reliable implementation of best
      practices for every patient. Specifically, optimizing outcomes requires a
      spectrum of research spanning basic science, drug development, clinical efficacy
      and effectiveness, health services, quality improvement, and implementation
      research. However, our rapid increase in understanding the mechanisms of health
      and disease and their treatment has far outpaced our ability to reliably provide
      that care, resulting in poor reliability and enormous variation in care. T3
      translational research studies attempt to answer questions surrounding reliable
      implementation of interventions, decreasing variations in care, and spreading
      effective therapies. To answer these questions, T3 research may use traditional
      research methodology such as randomized controlled trials (RCTs); however,
      various other approaches such as quasiexperimental designs (eg, time-series
      analysis) are often used. Although uncommon, T3 research has shown promise in not
      only improving process measures such as correct dosing of medications, but also
      outcome measures such as improved remission rates in patients with IBD. A more
      complete integration of T3 translational research into the more traditional
      research continuum is necessary if we are to achieve the best possible outcomes
      for our patients. 

PMID- 24107395
TI  - Antiviral therapy for chronic hepatitis B virus infection and development of
      hepatocellular carcinoma in a US population.
AB  - BACKGROUND & AIMS: Antiviral therapy could reduce the risk of hepatocellular
      carcinoma (HCC) among persons with chronic hepatitis B virus (HBV) infection. We
      evaluated the relationship between therapy for chronic HBV infection and HCC
      incidence using data from a longitudinal study of patients at 4 US healthcare
      centers. METHODS: We analyzed electronic health records of 2671 adult
      participants in the Chronic Hepatitis Cohort Study who were diagnosed with
      chronic HBV infection from 1992 through 2011 (49% Asian). Data analyzed were
      collected for a median of 5.2 years. Propensity-score adjustment was used to
      reduce bias, and Cox regression was used to estimate the relationship between
      antiviral treatment and HCC. The primary outcome was time to event of HCC
      incidence. RESULTS: Of study subjects, 3% developed HCC during follow-up period:
      20 cases among the 820 patients with a history of antiviral HBV therapy and 47
      cases among the 1851 untreated patients. In propensity-adjusted Cox regression,
      patients who received antiviral therapy had a lower risk of HCC than those who
      did not receive antiviral therapy (adjusted hazard ratio, 0.39; 95% confidence
      interval, 0.27-0.56; P < .001), after adjusting for abnormal level of alanine
      aminotransferase. In a subgroup analysis, antiviral treatment was associated with
      a lower risk of HCC after adjusting for serum markers of cirrhosis (adjusted
      hazard ratio, 0.24; 95% confidence interval, 0.15-0.39; P < .001). In a separate
      subgroup analysis of patients with available data on HBV DNA viral load, treated
      patients with viral loads >20,000 IU/mL had a significantly lower risk of HCC
      than untreated patients with viral loads >20,000 IU/mL. CONCLUSIONS: In a large
      geographically, clinically, and racially diverse US cohort, antiviral therapy for
      chronic HBV infection was associated with a reduced risk for HCC.

PMID- 24107398
TI  - Therapeutic approaches to the regulation of metabolism of high-density
      lipoprotein. Novel HDL-directed pharmacological intervention and exercise.
AB  - High-density lipoprotein (HDL) and low-density lipoprotein (LDL) particles
      transport cholesterol in plasma and play an important role in cellular
      cholesterol homeostasis, which influences cell function. The risk of coronary
      artery disease (CAD) associated with high levels of LDL-cholesterol (LDL-C) can
      be reduced by treatment with statins, which reduce LDL-C levels by inhibiting
      cellular cholesterol synthesis. However, patients who are treated with high doses
      of statins, especially secondary CAD prevention, regardless of their resulting
      LDL-C levels, are still at high risk of CAD. Therefore, there has been growing
      interest in HDL-directed therapies. Inhibitors of cholesteryl ester transfer
      protein (CETP) substantially increase HDL-C levels (by 31-138%). However, it is
      still unclear whether or not CETP inhibitors can reduce the risk of CAD
      associated with low HDL-C levels, while reconstituted HDL or apolipoprotein A-I
      mimetic peptides increase the functionality of HDL. Low levels of HDL-C are often
      complicated with metabolic disorders, including hypertriglyceridemia, metabolic
      syndrome, and type 2 diabetes mellitus, and lifestyle changes are effective for
      correcting these conditions. Physical activity and exercise training increase HDL
      C levels, especially HDL2-C levels, by multiple mechanisms. Therefore, although
      using HDL-directed therapies that increase HDL-C levels and/or improve the
      function of HDL is a reasonable approach for reducing the residual risk of CAD as
      a complement to LDL-C-lowering therapy, lifestyle modifications including
      exercise to improve metabolic disorders should be considered as the first option.

PMID- 24107399
TI  - Pleiotropic effects of peroxisome proliferator-activated receptor gamma and delta
      in vascular diseases.
AB  - Peroxisome proliferator-activated receptors gamma (PPARgamma) and delta
      (PPARdelta) are nuclear receptors that have significant physiological effects on
      glucose and lipid metabolism. Experimental studies in animal models of metabolic
      disease have demonstrated their effects on improving lipid profile, insulin
      sensitivity, and reducing inflammatory responses. PPARgamma and -delta are also
      expressed in the vasculature and their beneficial effects have been examined in
      various cardiovascular disease models such as atherosclerosis, hypertension,
      diabetic vascular complications, etc. using pharmacological ligands or genetic
      tools including viral vectors and transgenic mice. These studies suggest that
      PPARgamma and delta are antiinflammatory, antiatherogenic, antioxidant, and
      antifibrotic against vascular diseases. Several signaling pathways, effector
      molecules, as well as coactivators/repressors have been identified as responsible
      for the protective effects of PPARgamma and -delta in the vasculature. We discuss
      the pleiotropic effect of PPARgamma and delta in vascular dysfunction, including
      atherosclerosis, hypertension, vascular remodeling, vascular injury, and diabetic
      vasculopathy, in various animal models, and the major underlying mechanisms. We
      also compare the phenotypes of several endothelial cell/vascular smooth muscle
      specific PPARgamma and -delta knockout and overexpressing transgenic mice in
      various disease models, and the implications underlying the functional importance
      of vascular PPARgamma and delta in regulating whole-body homeostasis.

PMID- 24107400
TI  - Factors affecting enhanced video quality preferences.
AB  - The development of video quality metrics requires methods for measuring perceived
      video quality. Most of these metrics are designed and tested using databases of
      images degraded by compression and scored using opinion ratings. We studied video
      quality preferences for enhanced images of normally-sighted participants using
      the method of paired comparisons with a thorough statistical analysis.
      Participants (n=40) made pair-wise comparisons of high definition video clips
      enhanced at four different levels using a commercially available enhancement
      device. Perceptual scales were computed with binary logistic regression to
      estimate preferences for each level and to provide statistical inference of the
      differences among levels and the impact of other variables. While moderate
      preference for enhanced videos was found, two unexpected effects were also
      uncovered: 1) participants could be broadly classified into two groups: a) those
      who preferred enhancement ("Sharp") and b) those who disliked enhancement
      ("Smooth") and 2) enhancement preferences depended on video content, particularly
      for human faces to be enhanced less. The results suggest that algorithms to
      evaluate image quality (at least for enhancement) may need to be adjusted or
      applied differentially based on video content and viewer preferences. The
      possible impact of similar effects on image quality of compressed video needs to
      be evaluated. 

PMID- 24107401
TI  - Dual-tree cosine-modulated filter bank with linear-phase individual filters: an
      alternative shift-invariant and directional-selective transform.
AB  - Dual-tree transforms have recently received much attention for the properties of
      shift-invariance and directional-selectivity. However, their designs generally
      encounter fractional-delay constraints, and become more complicated for providing
      linear-phase (LP) individual filters and flexible directional-selectivity, two
      important properties in image processing. In this paper, we propose an
      alternative shift-invariant and directional-selective transform-the dual-tree
      cosine-modulated filter bank (DTCMFB). In the proposed DTCMFB, its primal and
      dual filter banks are derived by cosine-modulating one LP prototype filter, and
      thus its design involves no fractional-delay constraints. Meanwhile, the derived
      modulation technique guarantees each individual filter to be LP and the LP
      condition is satisfied without any constraint on the prototype filter. By
      separable operations, the DTCMFB is extended to two-dimensions. The resulting 2D
      DTCMFB can provide much more flexible directional-selectivity. Finally, several
      simulations are given to verify the proposed DTCMFB, and the experiments on
      nonlinear approximation and image denoising are presented to demonstrate its
      potential in image processing. 

PMID- 24107402
TI  - Polymorphism of the RAGE affects the serum inflammatory levels and risk of
      ischemic stroke in a Chinese population.
AB  - BACKGROUND: Increasing evidence shows that inflammation plays an important role
      in the occurrence and progression of acute ischemic stroke. The receptor for
      advanced glycation end products (RAGE) has been documented to involve in the
      pathogenic mechanisms of a variety of neurological diseases, including ischemic
      stroke (IS). However, the impact of RAGE gene polymorphisms on the susceptibility
      to IS has not been reported. We thus explored the association between RAGE gene
      polymorphisms and the susceptibility to IS. METHOD: A total of 384 patients with
      IS and 425 healthy controls were enrolled in this study. Three genetic
      polymorphisms of RAGE gene (82G/S, -429T/C and -374T/A) were determined. The
      serum levels of soluble RAGE (sRAGE), intetleukin-6 (IL-6), high sensitivity-C
      reaction protein (hs-CRP) and plasminogen activator inhibitor-1 (PAI-1) were
      detected. RESULTS: Among the studied polymorphisms, only the polymorphism at
      82G/S of RAGE gene was associated with the risk for ischemic stroke irrespective
      of the stroke subtypes. The 82S/S homozygote carriers had a significantly
      increased risk for ischemic stroke [adjusted odds ratio (OR): 2.297; p<0.001].
      The haplotype analyses showed that the C-429S82T-374 and T-429S82A-374 had higher
      risk to develop IS (OR=1.864 and 1.931, respectively, all p<0.01), while the C
      429G82T-374 showed a protective effect against IS susceptibility (OR=0.568,
      p=0.001). In addition, the 82S/S homozygote carriers had a higher inflammatory
      level compared with 82G/S and 82G/G genotypes, indicated by lower serum sRAGE
      level, higher serum IL-6, hs-CRP and PAI-1 levels. The polymorphisms at -374 and 
      429 loci did not influence the stroke risk and the above mentioned inflammation
      cytokines. CONCLUSION: Our results showed a close correlation between the 82G/S
      polymorphism and the susceptibility to IS, suggesting the 82G/S polymorphism may
      be used as a genetic marker for the prediction of stroke occurrence in high risk
      subjects.

PMID- 24107403
TI  - Small bowel obstruction and perforation attributed to tubo-ovarian abscess
      following 'D' and 'C'.
AB  - We report the case of a young woman who was admitted because of small bowel
      obstruction and localized peritonitis following a dilatation and curettage ('D'
      and 'C') of uterus in abortion. As infection, like tubo-ovarian abscess may
      complicate any abortion, it seems wise to ensure that it does not exist prior to
      performing a 'D' and 'C'. 

PMID- 24107404
TI  - Trials of antidiabetic drugs in amyotrophic lateral sclerosis: proceed with
      caution?
AB  - Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disorder with
      limited therapeutic options. Clinical trials of several drugs shown to be
      effective in the superoxide dismutase (SOD1) model of ALS have shown no or
      negative effects when tested in humans. Here we discuss the role of pioglitazone,
      a peroxisome proliferator-activated receptor-gamma agonist, which failed to show
      efficacy in a recently published phase II clinical trial of ALS patients. The
      antioxidant and anti-inflammatory properties of pioglitazone make it an
      attractive therapeutic candidate for neurodegenerative disorders. However, its
      antidiabetic and antidyslipidemic effects might be detrimental, as emerging
      evidence suggests that some features of the metabolic syndrome may be protective
      in ALS. A number of clinical studies show that dyslipidemia, high body mass
      index, and possibly diabetes mellitus type 2 are associated with better clinical
      outcomes in ALS. This is further corroborated by studies on transgenic animal
      models and immortalized neuronal cell lines. Finally, the intricate interplay
      between glucose/lipid metabolism and susceptibility to oxidative damage in
      neurons warrants a judicious approach in further trials of antidiabetic drugs in
      ALS.

PMID- 24107406
TI  - Preoperative protective stenting of the internal carotid artery in the management
      of complex head and neck paragangliomas: long-term results.
AB  - OBJECTIVES: To investigate the long-term results of preoperative stenting of the
      internal carotid artery (ICA) in complex head and neck paragangliomas (HNP) as
      well as to report on indications and technical details of the procedure. METHOD:
      A comprehensive retrospective review of patients affected by HNP, consecutively
      operated on and preoperatively treated with stenting of the ICA in a quaternary
      referral skull base center, was performed. RESULTS: Nineteen patients affected by
      complex HNP were identified, on whom 21 preoperative stenting procedures were
      performed. The mean follow-up period after stent insertion was 53.8 months; the
      patients' age ranged from 33 to 56 years. Fourteen patients were affected by
      tympanojugular paragangliomas, 4 by vagal paragangliomas and 1 by bilateral
      carotid body tumors. Five patients presented with recurrent tumors, while 7
      presented with multiple or bilateral HNP. There were no complications associated
      with endovascular procedures. Total tumor removal was accomplished in 52.4% of
      the cases with 1 recurrence. An advanced stage was the main factor conditioning
      total removal. Clinical control was obtained in 80% of the patients with residual
      disease. Total tumor removal from and around the ICA was obtained in 95.2% of the
      cases. Long-term stent patency was evident in 20 of 21 cases. CONCLUSIONS:
      Preoperative stenting of the ICA represents a safe and effective procedure in
      selected cases, obviating the need for balloon occlusion or bypass procedures and
      reducing the risk of intraoperative vascular injury.

PMID- 24107405
TI  - Linking structure and function: development of lateral spatial interactions in
      macaque monkeys.
AB  - Lateral spatial interactions among elements of a scene, which either enhance or
      degrade visual performance, are ubiquitous in vision. The neural mechanisms
      underlying lateral spatial interactions are a matter of debate, and various
      hypotheses have been proposed. Suppressive effects may be due to local inhibitory
      interactions, whereas facilitatory effects are typically ascribed either to the
      function of long-range horizontal projections in V1 or to uncertainty reduction.
      We investigated the development of lateral spatial interactions, facilitation and
      suppression, and compared their developmental profiles to those of potential
      underlying mechanisms in the visual system of infant macaques. Animals ranging in
      age from 10 weeks to 3 years were tested with a lateral masking paradigm. We
      found that suppressive interactions are present from very early in postnatal
      life, showing no change over the age range tested. However, facilitation develops
      slowly over the first year after birth. Our data suggest that the early
      maturation of suppressive interactions is related to the relatively mature
      receptive field properties of neurons in early visual cortical areas near birth
      in infant macaques, whereas the later maturation of facilitation is unlikely to
      be explained by development of local or long-range connectivity in primary visual
      cortex. Instead our data favor a late developing feedback or top-down cognitive
      process to explain the origin of facilitation. 

PMID- 24107407
TI  - Promoting universal financial protection: a policy analysis of universal health
      coverage in Costa Rica (1940-2000).
AB  - BACKGROUND: This paper explores the implementation and sustenance of universal
      health coverage (UHC) in Costa Rica, discussing the development of a social
      security scheme that covered 5% of the population in 1940, to one that finances
      and provides comprehensive healthcare to the whole population today. The scheme
      is financed by mandatory, tri-partite social insurance contributions complemented
      by tax funding to cover the poor. METHODS: The analysis takes a historical
      perspective and explores the policy process including the key actors and their
      relative influence in decision-making. Data were collected using qualitative
      research instruments, including a review of literature, institutional and other
      documents, and in-depth interviews with key informants. RESULTS: Key lessons to
      be learned are: i) population health was high on the political agenda in Costa
      Rica, in particular before the 1980s when UHC was enacted and the transfer of
      hospitals to the social security institution took place. Opposition to UHC could
      therefore be contained through negotiation and implemented incrementally despite
      the absence of real consensus among the policy elite; ii) since the 1960s, the
      social security institution has been responsible for UHC in Costa Rica. This
      institution enjoys financial and managerial autonomy relative to the general
      government, which has also facilitated the UHC policy implementation process;
      iii) UHC was simultaneously constructed on three pillars that reciprocally
      strengthened each other: increasing population coverage, increasing availability
      of financial resources based on solidarity financing mechanisms, and increasing
      service coverage, ultimately offering comprehensive health services and the same
      benefits to every resident in the country; iv) particularly before the 1980s, the
      fruits of economic growth were structurally invested in health and other
      universal social policies, in particular education and sanitation. The social
      security institution became a flagship of Costa Rica's national development
      strategy which reinforced its political importance and contributed to its longer
      term sustainability and that of UHC. CONCLUSIONS: UHC has been achieved in Costa
      Rica because it was supported at the highest political level within a favourable
      socio-economic and political context. Once achieved, UHC became an entitlement
      for the population and now enjoys broad public support.

PMID- 24107409
TI  - Searching for an optimal hand hygiene bundle: a meta-analysis.
AB  - Many studies have evaluated bundled interventions to improve hand hygiene
      compliance. However, there are few evidence-based recommendations on optimal
      interventions for implementation. We aimed to systematically review all studies
      on interventions to improve hand hygiene compliance to evaluate existing bundles
      and identify areas of promise to target high-quality studies. Adjusted risk
      ratios were pooled to assess common bundles. Of the 8148 studies evaluated, 6
      randomized controlled trials and 39 quasi-experimental studies met inclusion
      criteria. Three studies evaluated the interventions education, reminders,
      feedback, administrative support, and access to alcohol-based hand rub as a
      bundle, which was associated with improved hand hygiene compliance (pooled odds
      ratio [OR], 1.82; 95% confidence interval [CI], 1.69-1.97). Another bundle of
      education, reminders, and feedback evaluated in 3 studies was associated with
      improved compliance (pooled OR, 1.47; 95% CI, 1.12-1.94). These bundles should be
      further studied using high-quality study designs and compared with other
      interventions. 

PMID- 24107410
TI  - Consistent global approach on reporting of colistin doses to promote safe and
      effective use.

PMID- 24107411
TI  - Lupus erythematosus cells in bone marrow: the only clue to a previously
      unsuspected diagnosis of systemic lupus erythematosus.
AB  - BACKGROUND: Systemic lupus erythematosus (SLE) is an autoimmune multisystem
      disease characterized by the development of antinuclear antibodies. Nowadays
      considered outdated, lupus erythematosus (LE) cell preparation served as a
      screening test for SLE for decades. However, the importance of discovering LE
      cells on routine cytology cannot be overemphasized. CASE: We report the case of a
      30-year-old female in whom bone marrow aspiration (BMA) was performed during an
      investigative workup for pyrexia of unknown origin. The observation of LE cells
      in direct bone marrow smears (without the use of an anticoagulant) raised the
      suspicion of SLE, which was later confirmed by antinuclear antibody testing.
      CONCLUSION: In the present case, LE cells were observed on BMA performed for the
      investigation of fever of unknown origin. The unexpected observation of LE cells
      in BMA smears emphasizes the fact that good morphological observation of marrow
      aspirates can provide crucial clues to a previously unsuspected diagnosis.

PMID- 24107412
TI  - Evidence of the sensitivity of the MoCA alternate forms in monitoring cognitive
      change in early Alzheimer's disease.
AB  - BACKGROUND/AIMS: There is an increasing interest in using the Montreal Cognitive
      Assessment (MoCA) test as a monitoring tool in Alzheimer's disease (AD) in both
      research and clinical settings. Our aim was to investigate the utility of
      alternate forms of the MoCA in detecting cognitive deterioration in a sample of
      early AD patients followed longitudinally in an outpatient memory clinic. METHOD:
      Twenty-five patients with early-stage AD (prodromal or mild dementia) were
      administered the original version and one of two previously validated alternate
      forms of the MoCA within an interval of about 1 year. The decline over time and
      the rate of change of the MoCA were compared to the total score of a standardized
      neuropsychological assessment battery (Consortium to Establish a Registry of
      Alzheimer's Disease; CERAD-Plus). Responsiveness to change was determined by
      calculating standard response means and the respective effect sizes. RESULTS:
      Sixty percent of the sample showed a clinical decline on the clinical dementia
      rating (CDR) scale. There was significant deterioration in the MoCA and CERAD
      total scores. CONCLUSION: The results demonstrate that the MoCA is capable of
      detecting change over time and seems to be a valid tool with small to moderate
      sensitivity for monitoring cognitive change in early AD.

PMID- 24107413
TI  - Antenatal betamethasone associates with transient immunodepression in very low
      birth weight infants.
AB  - BACKGROUND: Antenatal betamethasone (BM) treatment for mothers at risk for
      premature delivery is effective in reducing neonatal morbidity. Immunodepression,
      defined as monocyte human leukocyte antigen (HLA)-DR expression <60%, is common
      in patients in intensive care. In very low birth weight (VLBW) infants,
      immunodepression correlates with gestational age and may predispose to
      infections. OBJECTIVES: To evaluate whether timing of antenatal BM associates
      with immunodepression in VLBW infants. METHODS: We determined monocyte HLA-DR
      expression by flow cytometry and measured 13 cytokines, cortisol, and BM in
      plasma from 56 VLBW infants. We calculated total glucocorticoid index as the sum
      of BM and cortisol at the ratio 33.3:1. RESULTS: HLA-DR expression both in cord
      (R(2) = 0.175, p = 0.033, n = 26) and on day 1 (R(2) = 0.125, p = 0.011, n = 51)
      showed an association with timing of BM. A short interval from BM to birth
      induced more pronounced and prolonged immunodepression, with lower HLA-DR% on
      postnatal day 7. On day 3, 25 infants (45%) met the criteria of immunodepression.
      HLA-DR expression correlated negatively with total glucocorticoid index (cord:
      R(2) = -0.573, p = 0.003, n = 13; day 1: R(2) = -0.213, p = 0.008, n = 32).
      Elapsed time from maternal BM correlated positively with concentrations of
      cytokines IL-6 and IL-10 on day 1. CONCLUSIONS: In VLBW infants, antenatal BM
      associated with transient immunodepression in a time-dependent manner.
      Suppression of both anti- and proinflammatory cytokines occurred. These effects
      may lead to an increased risk for later infections.

PMID- 24107414
TI  - TiO2 nanowires for potential facile integration of solar cells and electrochromic
      devices.
AB  - Self-powered systems usually consist of energy-acquisition components, energy
      storage components and functional components. The development of nanoscience and
      nanotechnology has greatly improved the performance of all the components of self
      powered systems. However, huge differences in the materials and configurations in
      the components cause large difficulties for integration and miniaturization of
      self-powered systems. Design and fabrication of different components in a self
      powered system with the same or similar materials/configurations should be able
      to make the above goal easier. In this work, a proof-of-concept experiment
      involving an integrated self-powered color-changing system consisting of TiO2
      nanowire based sandwich dye-sensitized solar cells (DSSCs) and electrochromic
      devices (ECDs) is designed and demonstrated. When sunlight illuminates the entire
      system, the DSSCs generate electrical power and turn the ECD to a darker color,
      dimming the light; by switching the connection polarity of the DSSCs, the lighter
      color can be regained, implying the potential application of this self-powered
      color-changing system for next generation sun glasses and smart windows. 

PMID- 24107415
TI  - Thyroglobulin wash testing in the surveillance of patients with thyroid
      carcinoma: proposal for a reflex test.
AB  - OBJECTIVE: Fine needle aspiration (FNA) cytology with thyroglobulin wash (TG-W)
      testing is recommended for follow-up of patients with differentiated thyroid
      carcinoma (DTC). The goal of this retrospective study was to determine if TG-W
      results contributed to the management of cases with positive FNA cytology. STUDY
      DESIGN: We reviewed data on patients with positive and suspicious cytology
      results, undergoing lymph node or thyroid bed FNA with TG-W testing as part of
      the preoperative or follow-up investigation of histologically proven DTC in our
      institution and from the literature. RESULTS: Of 30 positive/suspicious lymph
      node and thyroid bed FNAs in our institution, 22 (73%) had an elevated (>1 ng/ml)
      TG-W level. Seven of 8 TG-W-negative cases had DTC on follow-up. Of 577 cytology
      positive/suspicious FNAs in the literature, 557 (97%) showed TG-W-positive
      results. Fourteen of 20 TG-W-negative cases had DTC on follow-up. All patients in
      retrospective and literature review groups with positive and suspicious FNA
      cytology and available follow-up were treated for recurrent or metastatic disease
      regardless of TG-W results. CONCLUSION: Observations of both our and other
      institutions support a recommendation of reflex FNA TG-W testing only for cases
      with negative or indeterminate cytology results.

PMID- 24107416
TI  - Protein kinase C delta mediated cytotoxicity of 6-Hydroxydopamine via sustained
      extracellular signal-regulated kinase 1/2 activation in PC12 cells.
AB  - OBJECTIVES: The incidence of Parkinson's disease (PD) is increasing as the global
      population ages. 6-hydroxydopamine (6-OHDA) can induce PD-like neuropathology and
      biochemical changes in both in vitro and in vivo models. Therefore, clarification
      of the molecular mechanism of 6-OHDA-induced cell death might contribute to the
      understanding of the pathogenesis of PD. METHODS: With this goal in mind, we
      investigated the role of protein kinase C delta (PKC delta) in 6-OHDA-dependent
      death using the pheochromocytoma cell line, PC12. Cells were treated with 6-OHDA
      to induce toxicity with or without pretreatment using rottlerin (a PKC delta
      inhibitor), bisindolylmaleimide I (a general PKC inhibitor), Go6976 (a PKC
      inhibitor selective for calcium-dependent PKC isoforms), or phorbol-12-myristate
      13-acetate (PMA, a PKC activator). RESULTS: Phorbol-12-myristate-13-acetate
      decreased cell survival and increased the rate of apoptosis while rottlerin
      increased cell survival and decreased the rate of apoptosis. In contrast, neither
      bisindolylmaleimide I nor Go6976 affected 6-OHDA-induced cell death. Western
      analysis demonstrated that phosphorylation of PKC delta on Thr 505 as well as
      extracellular signal-regulated kinase (ERK) phosphorylation increased after
      exposure to 6-OHDA. This increase in PKC delta phosphorylation was potentiated by
      PMA. However, rottlerin attenuated the 6-OHDA-stimulated increase in PKC delta
      and ERK phosphorylation. CONCLUSION: These data suggest that PKC delta, rather
      than classic-type PKC (alpha, beta1, beta2, gamma), participates in 6-OHDA
      induced neurotoxicity in PC12 cells, and PKC delta activity is required for
      subsequent ERK activation during cell death.

PMID- 24107417
TI  - TAF-4 is required for the life extension of isp-1, clk-1 and tpk-1 Mit mutants.
AB  - While numerous life-extending manipulations have been discovered in the nematode
      Caenorhabditis elegans, one that remains most enigmatic is disruption of
      oxidative phosphorylation. In order to unravel how such an ostensibly deleterious
      manipulation can extend lifespan, we sought to identify the ensemble of nuclear
      transcription factors that are activated in response to defective mitochondrial
      electron transport chain (ETC) function. Using a feeding RNAi approach, we
      targeted over 400 transcription factors and identified 15 that, when reduced in
      function, reproducibly and differentially altered the development, stress
      response, and/or fecundity of isp-1(qm150) Mit mutants relative to wild-type
      animals. Seven of these transcription factors--AHA-1, CEH-18, HIF-1, JUN-1, NHR
      27, NHR-49 and the CREB homolog-1 (CRH-1)-interacting protein TAF-4--were also
      essential for isp-1 life extension. When we tested the involvement of these seven
      transcription factors in the life extension of two other Mit mutants, namely clk
      1(qm30) and tpk-1(qm162), TAF-4 and HIF-1 were consistently required. Our
      findings suggest that the Mit phenotype is under the control of multiple
      transcriptional responses, and that TAF-4 and HIF-1 may be part of a general
      signaling axis that specifies Mit mutant life extension.

PMID- 24107418
TI  - Adipokines as a link between obesity and chronic kidney disease.
AB  - Adipocytes secrete a number of bioactive adipokines that activate a variety of
      cell signaling pathways in central and peripheral tissues. Obesity is associated
      with the altered production of many adipokines and is linked to a number of
      pathologies. As an increase in body weight is directly associated with an
      increased risk for developing chronic kidney disease (CKD), there is significant
      interest in the link between obesity and renal dysfunction. Altered levels of the
      adipokines leptin, adiponectin, resistin, and visfatin can decrease the
      glomerular filtration rate and increase albuminuria, which are pathophysiological
      changes typical of CKD. Specifically, exposure of the glomerulus to altered
      adipokine levels can increase its permeability, fuse the podocytes, and cause
      mesangial cell hypertrophy, all of which alter the glomerular filtration rate. In
      addition, the adipokines leptin and adiponectin can act on tubular networks.
      Thus, adipokines can act on multiple cell types in the development of renal
      pathophysiology. Importantly, most studies have been performed using in vitro
      models, with future studies in vivo required to further elucidate the specific
      roles that adipokines play in the development and progression of CKD. 

PMID- 24107419
TI  - A 5-hydroxytryptamine receptor antagonist, sarpogrelate, reduces renal
      tubulointerstitial fibrosis by suppressing PAI-1.
AB  - A selective 5-hydroxytryptamine (5-HT) 2A receptor antagonist sarpogrelate (SG)
      blocks serotonin-induced platelet aggregation. It has been used clinically for
      the treatment of peripheral arterial disease. SG might be able to improve chronic
      ischemia, which contributes to renal fibrosis progression by maintaining renal
      microcirculation. This study investigated whether SG suppresses renal fibrosis.
      C57BL/6 mice fed a 0.2% adenine-containing diet for 6 wk developed severe
      tubulointerstitial fibrosis with kidney dysfunction. Subsequent SG treatment (30
      mg.kg(-1).day(-1)) for 4 wk improved these changes significantly by increasing
      peritubular blood flow in the fibrotic area, as evaluated by intravital
      microscopy and decreasing fibrin deposition. Urinary L-type fatty acid-binding
      protein, up-regulated by renal hypoxia, was also reduced by SG. Additionally,
      results showed that mRNA expression of plasminogen activator inhibitor-1 (PAI-1),
      which is known to promote fibrosis by mediating and enhancing transforming growth
      factor (TGF)-beta1 signaling, was suppressed by SG treatment in the kidney. In
      vitro experiments using cultured murine proximal tubular epithelial (mProx) cells
      revealed that incubation with TGF-beta1 and 5-HT increased PAI-1 mRNA expression;
      SG significantly reduced it. In conclusion, SG reduces renal fibrosis not only by
      the antithrombotic effect of maintaining peritubular blood flow but also by
      suppressing PAI-1 expression in renal tubular cells. 

PMID- 24107420
TI  - Silencing of p53 RNA through transarterial delivery ameliorates renal tubular
      injury and downregulates GSK-3beta expression after ischemia-reperfusion injury.
AB  - p53, a pivotal protein in the apoptotic pathway, has been identified as a
      mediator of transcriptional responses to ischemia-reperfusion (IR) injury. The
      characteristics and functional significance of the p53 response in vivo are
      largely unknown in IR-induced kidney injury. Therapeutic opportunities of
      delivering small interfering RNA (siRNA) via venous injection have gained
      recognition; however, systemic adverse effects of siRNA therapy should be
      considered. To prevent IR-induced kidney injury, we tested the efficacy of
      transarterial administration of siRNA targeting p53 (p53 siRNA). Female C57BL/6
      mice underwent unilateral renal artery ischemia for 30 min, followed by
      reperfusion. siRNA experiments utilized short hairpin (sh) RNA plasmid-based
      approaches. Transfection of shRNA was performed using cationic polymer
      transfection reagent. Injection of synthetic p53 shRNA into the left renal artery
      just after ischemia improved tubular injury, apoptosis, and the swelling of
      mitochondria in cells of the thick ascending limb of Henle (mTALH) at the outer
      medullary regions. Staining of upregulated p53 was colocalized with the inducible
      expression of glycogen synthase kinase-3beta (GSK-3beta) at mTALH after IR
      injury. p53 shRNA inhibited GSK-3beta expression and restored beta-catenin
      expression at mTALH. For IR-induced kidney injury, transarterial delivery of p53
      siRNA is an effective pharmacological intervention. Targeting siRNA to p53 leads
      to an attenuation of apoptosis and mitochondrial damage through the
      downregulation of GSK-3beta expression and upregulation of beta-catenin. Local
      delivery of vectors such as p53 siRNA through a transaortic catheter is
      clinically useful in reducing the adverse effect of siRNA-related therapy.

PMID- 24107421
TI  - Differential cystine and dibasic amino acid handling after loss of function of
      the amino acid transporter b0,+AT (Slc7a9) in mice.
AB  - Cystinuria is an autosomal recessive disease caused by mutations in SLC3A1 (rBAT)
      and SLC7A9 (b(0,+)AT). Gene targeting of the catalytic subunit (Slc7a9) in mice
      leads to excessive excretion of cystine, lysine, arginine, and ornithine. Here,
      we studied this non-type I cystinuria mouse model using gene expression analysis,
      Western blotting, clearance, and brush-border membrane vesicle (BBMV) uptake
      experiments to further characterize the renal and intestinal consequences of
      losing Slc7a9 function. The electrogenic and BBMV flux studies in the intestine
      suggested that arginine and ornithine are transported via other routes apart from
      system b(0,+). No remarkable gene expression changes were observed in other amino
      acid transporters and the peptide transporters in the intestine and kidney.
      Furthermore, the glomerular filtration rate (GFR) was reduced by 30% in knockout
      animals compared with wild-type animals. The fractional excretion of arginine was
      increased as expected (~100%), but fractional excretions of lysine (~35%),
      ornithine (~16%), and cystine (~11%) were less affected. Loss of function of
      b(0,+)AT reduced transport of cystine and arginine in renal BBMVs and completely
      abolished the exchanger activity of dibasic amino acids with neutral amino acids.
      In conclusion, loss of Slc7a9 function decreases the GFR and increases the
      excretion of several amino acids to a lesser extent than expected with no clear
      regulation at the mRNA and protein level of alternative transporters and no
      increased renal epithelial uptake. These observations indicate that transporters
      located in distal segments of the kidney and/or metabolic pathways may partially
      compensate for Slc7a9 loss of function. 

PMID- 24107422
TI  - Chronic unilateral ureteral obstruction in the neonatal mouse delays maturation
      of both kidneys and leads to late formation of atubular glomeruli.
AB  - Unilateral ureteral obstruction (UUO) in the adult mouse is the most widely used
      model of progressive renal disease: the proximal tubule is the nephron segment
      most severely affected and atubular glomeruli are formed after only 7 days of
      UUO. To determine the proximal nephron response to UUO in the maturing kidney,
      neonatal mice were examined 7 to 28 days following complete UUO under general
      anesthesia. Proximal tubular mass and maturation were determined by staining with
      Lotus tetragolonobus lectin. Superoxide was localized by nitroblue tetrazolium
      and collagen by Sirius red. Cell proliferation, cell death, PAX-2, megalin, alpha
      smooth muscle actin (alpha-SMA), renin, and fibronectin were identified by
      immunohistochemistry. During the first 14 days of ipsilateral UUO, despite
      oxidative stress (4-hydroxynonenal staining), glomerulotubular continuity was
      maintained and mitochondrial superoxide production persisted. However, from 14 to
      28 days, papillary growth was impaired and proximal tubules collapsed with
      increased apoptosis, autophagy, mitochondrial loss, and formation of atubular
      glomeruli. Fibronectin, alpha-SMA, and collagen increased in the obstructed
      kidney. Oxidative stress was present also in the contralateral kidney: renin was
      decreased, glomerulotubular maturation and papillary growth were delayed,
      followed by increased cortical and medullary growth. We conclude that neonatal
      UUO initially delays renal maturation and results in oxidative stress in both
      kidneys. In contrast to the adult, proximal tubular injury in the neonatal
      obstructed kidney is delayed at 14 days, followed only later by the formation of
      atubular glomeruli. Antioxidant therapies directed at proximal tubular
      mitochondria during early renal maturation may slow progression of congenital
      obstructive nephropathy. 

PMID- 24107423
TI  - Hormonal regulation of salt and water excretion: a mathematical model of whole
      kidney function and pressure natriuresis.
AB  - We present a lumped-nephron model that explicitly represents the main features of
      the underlying physiology, incorporating the major hormonal regulatory effects on
      both tubular and vascular function, and that accurately simulates hormonal
      regulation of renal salt and water excretion. This is the first model to
      explicitly couple glomerulovascular and medullary dynamics, and it is much more
      detailed in structure than existing whole organ models and renal portions of
      multiorgan models. In contrast to previous medullary models, which have only
      considered the antidiuretic state, our model is able to regulate water and sodium
      excretion over a variety of experimental conditions in good agreement with data
      from experimental studies of the rat. Since the properties of the vasculature and
      epithelia are explicitly represented, they can be altered to simulate
      pathophysiological conditions and pharmacological interventions. The model serves
      as an appropriate starting point for simulations of physiological,
      pathophysiological, and pharmacological renal conditions and for exploring the
      relationship between the extrarenal environment and renal excretory function in
      physiological and pathophysiological contexts. 

PMID- 24107424
TI  - Gamma subunit second transmembrane domain contributes to epithelial sodium
      channel gating and amiloride block.
AB  - The epithelial sodium channel (ENaC) is comprised of three homologous subunits.
      Channels composed solely of alpha- and beta-subunits (alphabeta-channels) exhibit
      a very high open probability (Po) and reduced sensitivity to amiloride, in
      contrast to channels composed of alpha- and gamma-subunits or of all three
      subunits (i.e., alphagamma- and alphabetagamma-channels). A mutant channel
      comprised of alpha- and beta-subunits, and a chimeric gamma-subunit where the
      region immediately preceding (beta12 and wrist) and encompassing the second
      transmembrane domain (TM2) was replaced with the corresponding region of the beta
      subunit (gamma-betaTM2), displayed characteristics reminiscent of alphabeta
      channels, including a reduced amiloride potency of block and a loss of Na(+) self
      inhibition (reflecting an increased Po). Substitutions at key pore-lining
      residues of the gamma-betaTM2 chimera enhanced the Na(+) self-inhibition
      response, whereas key gamma-subunit substitutions reduced the response.
      Furthermore, multiple sites within the TM2 domain of the gamma-subunit were
      required to confer high amiloride potency. In summary, we have identified novel
      pore-lining residues of the gamma-subunit of ENaC that are important for proper
      channel gating and its interaction with amiloride.

PMID- 24107425
TI  - A molecular update on pseudohypoaldosteronism type II.
AB  - The DCT (distal convoluted tubule) is the site of microregulation of water
      reabsorption and ion handling in the kidneys, which is mainly under the control
      of aldosterone. Aldosterone binds to and activates mineralocorticoid receptors,
      which ultimately lead to increased sodium reabsorption in the distal part of the
      nephron. Impairment of mineralocorticoid signal transduction results in
      resistance to aldosterone and mineralocorticoids, and, therefore, causes
      disturbances in electrolyte balance. Pseudohypoaldosteronism type II (PHAII) or
      familial hyperkalemic hypertension (FHHt) is a rare, autosomal dominant syndrome
      characterized by hypertension, hyperkalemia, metabolic acidosis, elevated or low
      aldosterone levels, and decreased plasma renin activity. PHAII is caused by
      mutations in the WNK isoforms (with no lysine kinase), which regulate the Na-Cl
      and Na-K-Cl cotransporters (NCC and NKCC2, respectively) and the renal outer
      medullary potassium (ROMK) channel in the DCT. This review focuses on new
      candidate genes such as KLHL3 and Cullin3, which are instrumental to unraveling
      novel signal transductions pathways involving NCC, to better understand the cause
      of PHAII along with the molecular mechanisms governing the pathophysiology of
      PHAII and its clinical manifestations.

PMID- 24107426
TI  - The impact of a "search and destroy" strategy for the prevention of methicillin
      resistant Staphylococcus aureus infections in an inpatient rehabilitation
      facility.
AB  - OBJECTIVE: To determine how the implementation of a methicillin-resistant
      Staphylococcus aureus (MRSA) control program in an inpatient rehabilitation
      facility (IRF) affects MRSA health care-associated infections (MRSA-HAIs).
      DESIGN: A retrospective chart review. SETTING: IRF affiliated with Vidant Medical
      Center, an 861-bed, acute-care teaching hospital for The Brody School of Medicine
      at East Carolina University. PATIENTS: Seventy-nine adult patients in the IRF who
      developed a MRSA-HAI from February 2005 through January 2011. INTERVENTIONS: Both
      the acute care hospital and the affiliated inpatient rehabilitation unit began
      screening 100% of admissions for MRSA nasal carriage, with decolonization of
      positive carriers, starting in February 2007. MAIN OUTCOME MEASUREMENTS: Yearly
      rates of MRSA-HAI per 1000 patient-days were compared in the IRF before and after
      the intervention. RESULTS: The weighted mean monthly infection rate before the
      intervention (February 2005 through January 2007) was 1.0714 per 1000 patient
      days compared with 0.6557 per 1000 patient days after the intervention (February
      2007 through January 2011). The decreased infection rates after the intervention
      were statistically significant (P = .0315). CONCLUSIONS: The implementation of an
      all-admissions MRSA screening program with decolonization of positive carriers in
      an IRF affiliated with an acute care hospital resulted in decreased MRSA-HAI
      rates in the IRF. When developing surveillance guidelines for MRSA, IRFs should
      be cognizant of infection rate trends and of the affiliated hospital's scope of
      policies and practices for infection prevention and control.

PMID- 24107427
TI  - The effect of lumbar support on the ultrasound measurements of trunk muscles: a
      single-blinded randomized controlled trial.
AB  - OBJECTIVES: To evaluate the effect of lumbopelvic belts on the thickness of
      lateral abdominal muscles and the cross-sectional area (CSA) of lumbar multifidus
      (LM) muscles. DESIGN: A single-blinded randomized controlled trial. SETTING: An
      academic and tertiary care referral spine and sports medicine center.
      PARTICIPANTS: Sixty healthy volunteers with no history of low back pain in the
      previous year. METHODS: The subjects were allocated into belt and control groups.
      Lumbar belts were given to the subjects in the belt group, and they were asked to
      use the belts during the study period except during sleeping hours. The subjects
      were assessed at baseline and at 4 and 8 weeks. MAIN OUTCOME MEASURES: The
      thickness of lateral abdominal muscles and the CSA of the LM muscles were
      measured by ultrasound with the patient in the hook-lying position on an
      examination table. RESULTS: The thickness of lateral abdominal muscles and the
      CSA of LM muscles on both sides decreased significantly among healthy subjects in
      the belt group after 8 weeks. CONCLUSION: The results of this study show that
      lumbopelvic belts might influence the ultrasonographic measurements of lateral
      abdominal and LM muscles and thereby spine stability.

PMID- 24107428
TI  - Seroprevalence of Toxoplasma gondii in donkeys (Equus asinus) in Italy.
AB  - Toxoplasmosis, an important zoonosis, can be transmitted by eating meat or
      drinking milk of animals infected with Toxoplasma gondii. Samples were collected
      from 238 donkeys in the year 2010 in Italy, which included 207 females and 31
      males of five breeds and crossbreeds with the average age 9 years (1 month-24
      years). Sera were tested for T. gondii antibodies using a latex agglutination
      test and the indirect fluorescent antibody test; 5 and 8% seropositivity were
      recorded, respectively. We found significant correlation between the presence of
      T. gondii antibodies and sex, age, grazing and presence of cats on the farms and
      their access to donkey feed. This is the first detection of T. gondii antibodies
      in donkeys in Italy.

PMID- 24107429
TI  - Dog age and breeds associated with high plasma cholesterol and triglyceride
      concentrations.
AB  - The objectives of this study were to set specific dog breed and sex standards for
      total cholesterol (T-Cho) and total triglyceride (T-TG) concentrations in dogs
      and to quantify the associations between dog age and concentrations of both
      lipids for different breeds. Increased age was associated with higher T-Cho and T
      TG concentrations in all five breed groups (P<0.05); T-Cho concentrations
      increased by 62.5 mg/dl between 9 and 16 years of age, and T-TG concentrations
      increased by 4.8 mg/dl per year of age (P<0.05). Miniature Schnauzers had the
      highest T-Cho concentrations of the studied breeds, while Miniature Dachshunds
      had the lowest concentrations (P<0.05). Veterinarians should consider dog age and
      breed when they use the lipid concentrations for diagnostic purposes.

PMID- 24107431
TI  - Diagnosis of congenital heart disease in an era of universal prenatal ultrasound
      screening in southwest Ohio.
AB  - OBJECTIVES: Diagnostic ultrasound is widespread in obstetric practice, yet many
      babies with major congenital heart disease remain undiagnosed. Factors affecting
      prenatal diagnosis of major congenital heart disease are not well understood.
      This study aims to document prenatal detection rates for major congenital heart
      disease in the Greater Cincinnati area, and identify factors associated with lack
      of prenatal diagnosis. METHODS: All living infants diagnosed with major
      congenital heart disease by 4 months of age at our centre were prospectively
      identified. Prenatal care data were obtained by parent interview. Neonatal
      records were reviewed for postnatal data. Obstetricians were contacted for
      diagnostic ultrasound data. RESULTS: A total of 100 infants met the inclusion
      criteria. In all, 95 infants were analysed, of whom 94 were offered diagnostic
      ultrasound. In all, 41 had a prenatal diagnosis of major congenital heart
      disease. The rate of prenatal detection varied by cardiac lesion, with aortic
      arch abnormalities, semilunar valve abnormalities, and venous anomalies going
      undetected in this sample. Among subjects without prenatal detection, the highest
      proportion consisted of those having Level 1 diagnostic ultrasound only (66%).
      Prenatal detection was not significantly influenced by maternal race, education
      level, income, or insurance type. CONCLUSIONS: Despite nearly universal
      diagnostic ultrasound, detection rates of major congenital heart disease remain
      low in southwest Ohio. An educational outreach programme including outflow tract
      sweeps for community-level obstetrical personnel may improve detection rates.

PMID- 24107430
TI  - Antagonistic effects of atipamezole, yohimbine and prazosin on medetomidine
      induced diuresis in healthy cats.
AB  - This study aimed to investigate and compare the antagonistic effects of
      atipamezole, yohimbine and prazosin on medetomidine-induced diuresis in healthy
      cats. Five cats were repeatedly used in each of the 9 groups. One group was not
      medicated. Cats in the other groups received 40 ug/kg medetomidine
      intramuscularly and saline (as the control), 160 ug/kg prazosin, or 40, 160 or
      480 ug/kg atipamezole or yohimbine intravenously 0.5 hr later. Volume, pH and
      specific gravity of urine; plasma arginine vasopressin (AVP) level; and
      creatinine, osmolality and electrolyte levels in both urine and plasma were
      measured. Both atipamezole and yohimbine, but not prazosin, antagonized
      medetomidine-induced diuresis. The antidiuretic effect of atipamezole was more
      potent than that of yohimbine, but was not dose dependent, in contrast to the
      effect of yohimbine at the tested doses. Both atipamezole and yohimbine reversed
      medetomidine-induced decreases in both urine specific gravity and osmolality and
      increases in plasma osmolality and free-water clearance. Antidiuresis of either
      atipamezole or yohimbine was not related to the area under the curve for AVP
      level, although the highest dose of both atipamezole and yohimbine initially and
      temporarily increased plasma AVP levels, suggesting that this may partly
      influence the antidiuretic effects of both agents. The diuretic effect of
      medetomidine in cats may be mediated by alpha2-adrenoceptors, but not alpha1
      adrenoceptors. Atipamezole and yohimbine can be used as antagonistic agents
      against medetomidine-induced diuresis in healthy cats.

PMID- 24107433
TI  - Preserved and violated dignity in surgical practice - nurses' experiences.
AB  - The aim of this article was to obtain an understanding of what is experienced as
      human dignity by nurses in surgical practice. In order to obtain experiences from
      practice, the critical incident technique was chosen. A total of 11 nurses from
      surgical practice wrote 49 stories about positive and negative incidents. The
      text was analysed using hermeneutical text interpretation. The findings revealed
      patient dignity in terms of preserved dignity, that is, healthcare professionals
      paid attention to the patient. Nurses experienced preserved dignity when
      healthcare professionals allowed the patient to tell their story, allowed
      themselves to get close to the patient and in turn received the patient's trust.
      Violated dignity included circumstances when the nurses were forced to see what
      they did not want to see. Nurses experienced violated dignity when healthcare
      professionals behaved rudely towards the patient, acted as if he or she was
      invisible or humiliated the patient at the end of life. 

PMID- 24107432
TI  - Abnormalities in auditory efferent activities in children with selective mutism.
AB  - Two efferent feedback pathways to the auditory periphery may play a role in
      monitoring self-vocalization: the middle-ear acoustic reflex (MEAR) and the
      medial olivocochlear bundle (MOCB) reflex. Since most studies regarding the role
      of auditory efferent activity during self-vocalization were conducted in animals,
      human data are scarce. The working premise of the current study was that
      selective mutism (SM), a rare psychiatric disorder characterized by consistent
      failure to speak in specific social situations despite the ability to speak
      normally in other situations, may serve as a human model for studying the
      potential involvement of auditory efferent activity during self-vocalization. For
      this purpose, auditory efferent function was assessed in a group of 31 children
      with SM and compared to that of a group of 31 normally developing control
      children (mean age 8.9 and 8.8 years, respectively). All children exhibited
      normal hearing thresholds and type A tympanograms. MEAR and MOCB functions were
      evaluated by means of acoustic reflex thresholds and decay functions and the
      suppression of transient-evoked otoacoustic emissions, respectively. Auditory
      afferent function was tested by means of auditory brainstem responses (ABR).
      Results indicated a significantly higher proportion of children with abnormal
      MEAR and MOCB function in the SM group (58.6 and 38%, respectively) compared to
      controls (9.7 and 8%, respectively). The prevalence of abnormal MEAR and/or MOCB
      function was significantly higher in the SM group (71%) compared to controls
      (16%). Intact afferent function manifested in normal absolute and interpeak
      latencies of ABR components in all children. The finding of aberrant efferent
      auditory function in a large proportion of children with SM provides further
      support for the notion that MEAR and MOCB may play a significant role in the
      process of self-vocalization.

PMID- 24107435
TI  - Balancing efficiency, equity and feasibility of HIV treatment in South Africa -
      development of programmatic guidance.
AB  - South Africa, the country with the largest HIV epidemic worldwide, has been
      scaling up treatment since 2003 and is rapidly expanding its eligibility
      criteria. The HIV treatment programme has achieved significant results, and had
      1.8 million people on treatment per 2011. Despite these achievements, it is now
      facing major concerns regarding (i) efficiency: alternative treatment policies
      may save more lives for the same budget; (ii) equity: there are large
      inequalities in who receives treatment; (iii) feasibility: still only 52% of the
      eligible population receives treatment.Hence, decisions on the design of the
      present HIV treatment programme in South Africa can be considered suboptimal. We
      argue there are two fundamental reasons to this. First, while there is a rapidly
      growing evidence-base to guide priority setting decisions on HIV treatment, its
      included studies typically consider only one criterion at a time and thus fail to
      capture the broad range of values that stakeholders have. Second, priority
      setting on HIV treatment is a highly political process but it seems no adequate
      participatory processes are in place to incorporate stakeholders' views and
      evidences of all sorts.We propose an alternative approach that provides a better
      evidence base and outlines a fair policy process to improve priority setting in
      HIV treatment. The approach integrates two increasingly important frameworks on
      health care priority setting: accountability for reasonableness (A4R) to foster
      procedural fairness, and multi-criteria decision analysis (MCDA) to construct an
      evidence-base on the feasibility, efficiency, and equity of programme options
      including trade-offs. The approach provides programmatic guidance on the choice
      of treatment strategies at various decisions levels based on a sound conceptual
      framework, and holds large potential to improve HIV priority setting in South
      Africa. 

PMID- 24107436
TI  - Cardiovascular consequences of bronchopulmonary dysplasia in prematurely born
      preschool children.
AB  - BACKGROUND: A limited number of studies have reported various short-term
      cardiovascular changes in bronchopulmonary dysplasia (BPD) patients in the
      postsurfactant era. Little is known about the course of these changes in children
      with BPD. OBJECTIVES: It was the aim of this study to investigate cardiovascular
      consequences of BPD at preschool ages and to find out possible risk factors
      related to cardiovascular sequelae. METHODS: Prematurely born children with (n =
      21) and without BPD (n = 20) were evaluated with conventional and myocardial
      tissue Doppler echocardiography at the age of 2-4 years. RESULTS: BPD patients
      had a decreased pulmonary artery acceleration time and higher left and right
      ventricular myocardial performance indexes, consistent with higher pulmonary
      pressures and impaired biventricular systolic and diastolic functions at
      preschool ages. Low birth weight, disease severity and postnatal cumulative
      steroid dose were related to these changes. CONCLUSION: Negative effects of BPD
      on global cardiac performances of both ventricles and pulmonary arterial pressure
      persist up to preschool ages.

PMID- 24107438
TI  - The tilapias' chromosomes influencing sex determination.
AB  - The sex chromosomes of tilapias (family Cichlidae; genera Oreochromis,
      Sarotherodon and Tilapia) have been studied for over 50 years, which has gained
      interest from both agricultural and basic scientific perspectives. Several
      closely related tilapia species which can interbreed have been studied, and it
      has been repeatedly demonstrated that there is variation within and between
      species in the chromosomal sex-determination mechanism. Both male and female
      heterogametic sex-determination systems have been characterized, as well as
      epistatic and environmental influences on sex determination. Three different
      linkage groups (LG1, LG3 and LG23) have been identified as sex-associated
      chromosomes and have been subjected to further cytogenetic research and analyses
      of the genes located around the sex-determining region. Variation in the genetic
      and physical characteristics of the sex chromosomes makes tilapias an excellent
      model system for studying the evolution of vertebrate sex chromosomes. This
      review summarizes the progress made along 5 decades of research and the current
      knowledge of the tilapias' sex chromosomes.

PMID- 24107437
TI  - QUALZICE: a QUALitative exploration of the experiences of the participants from
      the ZICE clinical trial (metastatic breast cancer) receiving intravenous or oral
      bisphosphonates.
AB  - BACKGROUND: This qualitative sub-study aimed to explore the experiences of
      participants on the National Cancer Research Institute ZICE clinical trial, a
      randomised trial assessing two types of bisphosphonate treatment in breast cancer
      patients with bone metastases. Participants in the clinical trial were randomly
      allocated to receive either zoledronate, delivered by an intravenous (IV)
      infusion at clinic, or oral ibandronate, taken at home. METHODS: Qualitative
      research interviews were conducted with participant groups organised by treatment
      and location. Interviews covered experiences and understanding of bisphosphonate
      treatment, the experience of the delivery mechanisms (IV or oral), side effects
      and benefits, and quality of life issues. The analytic framework was
      interpretative phenomenological analysis. RESULTS: This paper reports on one of
      four superordinate themes: participants' experience of the ZICE trial, which
      explores the participants' experiences with clinical trial-related processes.
      Results show that participants were generally satisfied with their randomised
      treatment, although most participants had an initial preference for oral
      bisphosphonates. Some difficulties were reported from participants for both
      interventions: needle phobia, poor veins, difficulty with swallowing and gastric
      side effects, but pain control was improved with both modes of delivery. However,
      the infused bisphosphonate was reported to lose effectiveness after three weeks
      for some participants, whereas the oral bisphosphonate was reported to give
      consistent pain control. Geographical location and distance to travel made little
      difference to convenience of access to clinic as the reported lengths of travel
      time were similar due to traffic congestion in the urban areas. Most participants
      understood the trial processes, such as randomisation, and information about
      bisphosphonates but some participants showed little understanding of certain
      aspects of the trial. Some participants reported difficulties in accessing dental
      treatment due to their dentist's perceptions of bisphosphonate treatment.
      CONCLUSIONS: In trials of medicinal products, especially when testing for non
      inferiority, participants' preferences and idiosyncrasies in relation to
      treatments should not be assumed. This study has shown that in a trial context,
      participants' views can usefully add to the main trial outcomes and they should
      be taken into account when prescribing in the real world. TRIAL REGISTRATION:
      ISRCTN13914201. Main ZICE MREC: 05/MRE09/57. CRUK E/04/022.

PMID- 24107439
TI  - Automated and manual human papilloma virus in situ hybridization and p16
      immunohistochemistry: comparison in metastatic oropharyngeal carcinoma.
AB  - OBJECTIVES: We compared the efficacy of automated and manual human papilloma
      virus (HPV) in situ hybridization (ISH) and p16 immunohistochemical staining
      (IHC) in fine needle aspiration (FNA) of metastatic oropharyngeal carcinoma.
      STUDY DESIGN: A total of 41 FNA cell blocks (CB) were evaluated. HPV ISH was
      interpreted as positive if a minimum of one tumor cell showed punctate dot-like
      nuclear positivity. p16 was interpreted as positive if >=70% of tumor cells
      showed brown nuclear and cytoplasmic staining. RESULTS: Thirty of 41 CB (73%)
      were positive by automated HPV ISH, 25 of 41 CB (60%) with manual HPV ISH.
      Eighteen of 41 CB (43%) were positive for p16 IHC. Twelve of 41 CB (29%) with
      automated HPV ISH and 2 of 41 CB (4%) with the manual method were positive at 10*
      magnification. Three of 41 CB (7%) with automated HPV ISH and 14 of 41 CB (34%)
      with the manual method were positive at 20* magnification. Fifteen of 41 CB (36%)
      with automated HPV ISH and 9 of 41 CB (21%) with the manual method were positive
      at 40-60* magnification. CONCLUSION: Automated HPV ISH plays a more significant
      role in determining the HPV status in CB. However, the failure to use high
      magnification in the evaluation can give false-negative results.

PMID- 24107440
TI  - Haploidentical stem cell transplantation in two children with
      mucopolysaccharidosis VI: clinical and biochemical outcome.
AB  - BACKGROUND: Mucopolysaccharidosis VI (MPS VI) is an autosomal recessive
      progressive multiorgan disorder due to mutation in the gene encoding the enzyme
      Arylsulfatase B (ARSB). Dysfunctional ARSB causes lysosomal accumulation of
      glycosaminoglycans (GAG). Currently, enzyme replacement therapy (ERT) is
      preferred to hematopoietic stem cell transplantation (SCT) due to the treatment
      related risks of the latter. However, ERT constitutes an expensive life-long
      treatment. Increased experience and safety of SCT-procedures in recent years
      suggest that SCT should be further explored as a treatment option.This is the
      first report on haploidentical SCT in patients with MPS VI. The primary objective
      was to assess the treatment safety and clinical and biochemical outcome. PATIENTS
      AND METHODS: Two siblings diagnosed with MPS VI at 10 months of age and at birth
      with genotype p.C192R, reported as mild to intermediate phenotype, underwent
      unrelated umbilical cord blood transplantation pre-symptomatic. Due to graft
      failure, both patients were urgently re-transplantated with haploidentical SCT
      with the father as donor. Continuous clinical and biochemical status was
      monitored and concluded 3.8 and 4.6 years after the haploidentical SCT. RESULTS:
      Haploidentical SCT resulted in prompt and sustained engraftment. Complete donor
      chimerism was achieved in both patients, apart from mixed B cells chimerism in
      patient 2. ARSB activity in leukocytes post transplant increased from 0.0 to 19.0
      MUkat/kg protein (patient 1) and from 3.6 to 17.9 MUkat/kg protein (patient 2)
      (ref. 17-40). Total urinary GAG normalized in both patients, although patient 2's
      values slightly exceed normal range since 6 months. However, dermatan sulfaturia
      was substantially normalized since 16 months and 12 months post-SCT,
      respectively. Height was -1.85 SD and -1.27 SD at follow-up. Patient 1 had
      impaired visual acuity and discrete hepatomegaly. Patient 2 had elevated
      intraocular pressure and X-ray revealed steep acetabular angles and slightly
      flattened lumbar vertebrae. CONCLUSION: This study demonstrates that young
      children with MPS VI tolerate haploidentical SCT. Normalization of enzyme
      production and dermatan sulfaturia indicates correction of the inborn error of
      metabolism and coincide with no obvious symptoms of progressive MPS VI up to 4.6
      years post-SCT.

PMID- 24107441
TI  - Growth mechanisms and process window for InAs V-shaped nanoscale membranes on
      Si[001].
AB  - Organized growth of high aspect-ratio nanostructures such as membranes is
      interesting for opto-electronic and energy harvesting applications. Recently, we
      reported a new form of InAs nano-membranes grown on Si substrates with enhanced
      light scattering properties. In this paper we study how to tune the morphology of
      the membranes by changing the growth conditions. We examine the role of the V/III
      ratio, substrate temperature, mask opening size and inter-hole distances in
      determining the size and shape of the structures. Our results show that the nano
      membranes form by a combination of the growth mechanisms of nanowires and the
      Stranski-Krastanov type of quantum dots: in analogy with nanowires, the length of
      the membranes strongly depends on the growth temperature and the V/III ratio; the
      inter-hole distance of the sample determines two different growth regimes:
      competitive growth for small distances and an independent regime for larger
      distances. Conversely, and similarly to quantum dots, the width of the nano
      membranes increases with the growth temperature and does not exhibit dependence
      on the V/III ratio. These results constitute an important step towards achieving
      rational design of high aspect-ratio nanostructures. 

PMID- 24107442
TI  - Organizations' Ways of Employing Early Retirees: The Role of Age-Based HR
      Policies.
AB  - PURPOSE OF THE STUDY: We examine whether from an organizational perspective it is
      possible to distinguish different ways of employing early retirees and explore
      how the employment of early retirees is related to the application of 4 age-based
      human resource (HR) policies, namely demotion, offering training opportunities to
      older workers, offering early retirement, and allowing flexible working hours.
      DESIGN AND METHODS: We perform a latent class analysis on a sample of 998 Dutch
      organizations in order to categorize them based on 3 dimensions of their
      employment of early retirees. We then run a multinomial logistic regression to
      relate the employment of early retirees to the 4 age-based HR policies. RESULTS:
      We distinguish 4 types of organizations based on their way of employing early
      retirees: nonusers (52.6%), users for mainly standard work (20.8%), users for
      mainly nonstandard work (9.8%), and users for standard and nonstandard work
      (16.7%). We find that organizations that apply demotion, offer early retirement,
      and allow flexible working hours are more likely to be users for mainly standard
      work. Also, organizations that do not offer early retirement are less likely to
      employ early retirees. IMPLICATIONS: Age-based HR policies, especially demotion,
      offering early retirement, and allowing flexible working hours, are conducive to
      the employment of early retirees for mainly standard work. Broader implementation
      of these policies may provide opportunities for older workers to make a more
      gradual transition from work to retirement.

PMID- 24107443
TI  - Computer proficiency questionnaire: assessing low and high computer proficient
      seniors.
AB  - PURPOSE OF THE STUDY: Computers and the Internet have the potential to enrich the
      lives of seniors and aid in the performance of important tasks required for
      independent living. A prerequisite for reaping these benefits is having the
      skills needed to use these systems, which is highly dependent on proper training.
      One prerequisite for efficient and effective training is being able to gauge
      current levels of proficiency. We developed a new measure (the Computer
      Proficiency Questionnaire, or CPQ) to measure computer proficiency in the domains
      of computer basics, printing, communication, Internet, calendaring software, and
      multimedia use. Our aim was to develop a measure appropriate for individuals with
      a wide range of proficiencies from noncomputer users to extremely skilled users.
      DESIGN AND METHODS: To assess the reliability and validity of the CPQ, a diverse
      sample of older adults, including 276 older adults with no or minimal computer
      experience, was recruited and asked to complete the CPQ. RESULTS: The CPQ
      demonstrated excellent reliability (Cronbach's alpha = .98), with subscale
      reliabilities ranging from .86 to .97. Age, computer use, and general technology
      use all predicted CPQ scores. Factor analysis revealed three main factors of
      proficiency related to Internet and e-mail use; communication and calendaring;
      and computer basics. Based on our findings, we also developed a short-form CPQ
      (CPQ-12) with similar properties but 21 fewer questions. IMPLICATIONS: The CPQ
      and CPQ-12 are useful tools to gauge computer proficiency for training and
      research purposes, even among low computer proficient older adults.

PMID- 24107444
TI  - Function and dysfunction of presenilin.
AB  - The presenilin(PS) genes harbor approximately 90% of the identified mutations
      linked to familial forms of Alzheimer's disease, and the presenilin (PS) proteins
      are essential components of the gamma-secretase complex involved in the
      proteolytic cleavage of type I receptors, such as Notch and the amyloid precursor
      protein. Genetic analysis employing cell type-specific conditional knockout
      technology highlighted the importance of PS in the adult brain, including
      learning and memory, synaptic function and age-dependent neuronal survival. In
      the central synapse, PS regulates neurotransmitter release, short- and long-term
      synaptic plasticity and calcium homeostasis. However, the molecular mechanisms by
      which PS maintains these essential functions are less clear. Although many gamma
      secretase substrates have been identified, their physiological relevance is often
      unclear. The findings that nicastrin and PS conditional knockout mice exhibit
      similar deficits in memory and age-dependent neurodegeneration are consistent
      with the notion that gamma-secretase-dependent activities of PS are required for
      the maintenance of memory and neuronal survival, though the gamma-secretase
      physiological substrates, Notch receptors, are not targets of PS in the adult
      brain. Thus, despite of the intense interest in PS since its identification in
      1995, more work is needed to define the molecular and cellular mechanisms by
      which PS controls brain functions and the dysfunction conferred by disease
      causing mutations.

PMID- 24107445
TI  - BRAF V600E is a determinant of sensitivity to proteasome inhibitors.
AB  - A critical step toward defining tailored therapy in patients with cancer is the
      identification of genetic interactions that may impair-or boost-the efficacy of
      selected therapeutic approaches. Cell models able to recapitulate combinations of
      genetic aberrations are important to find drug-genotype interactions poorly
      affected by the heterogeneous genetics of human tumors. In order to identify
      novel pharmacogenomic relationships, we employed an isogenic cell panel that
      reconstructs cancer genetic scenarios. We screened a library of 43 compounds in
      human hTERT-HME1 epithelial cells in which PTEN or RB1 were silenced in
      combination with the targeted knockin of cancer-associated mutations in EGFR,
      KRAS, BRAF, or PIK3CA oncogenes. Statistical analysis and clustering algorithms
      were applied to display similar drug response profiles and mutation-specific
      patterns of activity. From the screen, we discovered that proteasome inhibitors
      show selectivity toward BRAF V600E-mutant cells, irrespective of PTEN or RB1
      expression. Preferential targeting of BRAF-mutant cells by proteasome inhibitors
      was corroborated in a second BRAF V600E isogenic model, as well as in a panel of
      colorectal cancer cell lines by the use of the proteasome inhibitor carfilzomib.
      Notably, carfilzomib also showed striking in vivo activity in a BRAF-mutant human
      colorectal cancer xenograft model. Vulnerability to proteasome inhibitors is
      dependent on persistent BRAF signaling, because BRAF V600E blockade by PLX4720
      reversed sensitivity to carfilzomib in BRAF-mutant colorectal cancer cells. Our
      findings indicated that proteasome inhibition might represent a valuable
      targeting strategy in BRAF V600E-mutant colorectal tumors.

PMID- 24107446
TI  - Microtubule dynamics control tail retraction in migrating vascular endothelial
      cells.
AB  - Drugs that target microtubules are potent inhibitors of angiogenesis, but their
      mechanism of action is not well understood. To explore this, we treated human
      umbilical vein endothelial cells with paclitaxel, vinblastine, and colchicine and
      measured the effects on microtubule dynamics and cell motility. In general, lower
      drug concentrations suppressed microtubule dynamics and inhibited cell migration
      whereas higher concentrations were needed to inhibit cell division; however,
      surprisingly, large drug-dependent differences were seen in the relative
      concentrations needed to inhibit these two processes. Suppression of microtubule
      dynamics did not significantly affect excursions of lamellipodia away from the
      nucleus or prevent cells from elongating; but, it did inhibit retraction of the
      trailing edges that are normally enriched in dynamic microtubules, thereby
      limiting cell locomotion. Complete removal of microtubules with a high
      vinblastine concentration caused a loss of polarity that resulted in roundish,
      rather than elongated, cells, rapid but nondirectional membrane activity, and
      little cell movement. The results are consistent with a model in which more
      static microtubules stabilize the leading edge of migrating cells, whereas more
      dynamic microtubules locate to the rear where they can remodel and allow tail
      retraction. Suppressing microtubule dynamics interferes with tail retraction, but
      removal of microtubules destroys the asymmetry needed for cell elongation and
      directional motility. The prediction that suppressing microtubule dynamics might
      be sufficient to prevent angiogenesis was supported by showing that low
      concentrations of paclitaxel could prevent the formation of capillary-like
      structures in an in vitro tube formation assay.

PMID- 24107447
TI  - Selective disruption of rb-raf-1 kinase interaction inhibits pancreatic
      adenocarcinoma growth irrespective of gemcitabine sensitivity.
AB  - Inactivation of the retinoblastoma (Rb) tumor suppressor protein is widespread in
      human cancers. Inactivation of Rb is thought to be initiated by association with
      Raf-1 (C-Raf) kinase, and here we determined how RRD-251, a disruptor of the Rb
      Raf-1 interaction, affects pancreatic tumor progression. Assessment of phospho-Rb
      levels in resected human pancreatic tumor specimens by immunohistochemistry (n =
      95) showed that increased Rb phosphorylation correlated with increasing grade of
      resected human pancreatic adenocarcinomas (P = 0.0272), which correlated with
      reduced overall patient survival (P = 0.0186). To define the antitumor effects of
      RRD-251 (50 MUmol/L), cell-cycle analyses, senescence, cell viability, cell
      migration, anchorage-independent growth, angiogenic tubule formation and invasion
      assays were conducted on gemcitabine-sensitive and -resistant pancreatic cancer
      cells. RRD-251 prevented S-phase entry, induced senescence and apoptosis, and
      inhibited anchorage-independent growth and invasion (P < 0.01). Drug efficacy on
      subcutaneous and orthotopic xenograft models was tested by intraperitoneal
      injections of RRD-251 (50 mg/kg) alone or in combination with gemcitabine (250
      mg/kg). RRD-251 significantly reduced tumor growth in vivo accompanied by reduced
      Rb phosphorylation and lymph node and liver metastasis (P < 0.01). Combination of
      RRD-251 with gemcitabine showed cooperative effect on tumor growth (P < 0.01). In
      conclusion, disruption of the Rb-Raf-1 interaction significantly reduces the
      malignant properties of pancreatic cancer cells irrespective of their gemcitabine
      sensitivity. Selective targeting of Rb-Raf-1 interaction might be a promising
      strategy targeting pancreatic cancer.

PMID- 24107449
TI  - Molecular predictors of sensitivity to the insulin-like growth factor 1 receptor
      inhibitor Figitumumab (CP-751,871).
AB  - Figitumumab (CP-751,871), a potent and fully human monoclonal anti-insulin-like
      growth factor 1 receptor (IGF1R) antibody, has been investigated in clinical
      trials of several solid tumors. To identify biomarkers of sensitivity and
      resistance to figitumumab, its in vitro antiproliferative activity was analyzed
      in a panel of 93 cancer cell lines by combining in vitro screens with extensive
      molecular profiling of genomic aberrations. Overall response was bimodal and the
      majority of cell lines were resistant to figitumumab. Nine of 15 sensitive cell
      lines were derived from colon cancers. Correlations between genomic
      characteristics of cancer cell lines with figitumumab antiproliferative activity
      revealed that components of the IGF pathway, including IRS2 (insulin receptor
      substrate 2) and IGFBP5 (IGF-binding protein 5), played a pivotal role in
      determining the sensitivity of tumors to single-agent figitumumab. Tissue
      specific differences among the top predictive genes highlight the need for tumor
      specific patient selection strategies. For the first time, we report that
      alteration or expression of the MYB oncogene is associated with sensitivity to
      IGF1R inhibitors. MYB is dysregulated in hematologic and epithelial tumors, and
      IGF1R inhibition may represent a novel therapeutic opportunity. Although growth
      inhibitory activity with single-agent figitumumab was relatively rare, nine
      combinations comprising figitumumab plus chemotherapeutic agents or other
      targeted agents exhibited properties of synergy. Inhibitors of the ERBB family
      were frequently synergistic and potential biomarkers of drug synergy were
      identified. Several biomarkers of antiproliferative activity of figitumumab both
      alone and in combination with other therapies may inform the design of clinical
      trials evaluating IGF1R inhibitors.

PMID- 24107448
TI  - Small molecule inhibition of PAX3-FOXO1 through AKT activation suppresses
      malignant phenotypes of alveolar rhabdomyosarcoma.
AB  - Alveolar rhabdomyosarcoma comprises a rare highly malignant tumor presumed to be
      associated with skeletal muscle lineage in children. The hallmark of the majority
      of alveolar rhabdomyosarcoma is a chromosomal translocation that generates the
      PAX3-FOXO1 fusion protein, which is an oncogenic transcription factor responsible
      for the development of the malignant phenotype of this tumor. Alveolar
      rhabdomyosarcoma cells are dependent on the oncogenic activity of PAX3-FOXO1, and
      its expression status in alveolar rhabdomyosarcoma tumors correlates with worst
      patient outcome, suggesting that blocking this activity of PAX3-FOXO1 may be an
      attractive therapeutic strategy against this fusion-positive disease. In this
      study, we screened small molecule chemical libraries for inhibitors of PAX3-FOXO1
      transcriptional activity using a cell-based readout system. We identified the
      Sarco/endoplasmic reticulum Ca(2+)-ATPases (SERCA) inhibitor thapsigargin as an
      effective inhibitor of PAX3-FOXO1. Subsequent experiments in alveolar
      rhabdomyosarcoma cells showed that activation of AKT by thapsigargin inhibited
      PAX3-FOXO1 activity via phosphorylation. Moreover, this AKT activation appears to
      be associated with the effects of thapsigargin on intracellular calcium levels.
      Furthermore, thapsigargin inhibited the binding of PAX3-FOXO1 to target genes and
      subsequently promoted its proteasomal degradation. In addition, thapsigargin
      treatment decreases the growth and invasive capacity of alveolar rhabdomyosarcoma
      cells while inducing apoptosis in vitro. Finally, thapsigargin can suppress the
      growth of an alveolar rhabdomyosarcoma xenograft tumor in vivo. These data reveal
      that thapsigargin-induced activation of AKT is an effective mechanism to inhibit
      PAX3-FOXO1 and a potential agent for targeted therapy against alveolar
      rhabdomyosarcoma.

PMID- 24107450
TI  - Targeting blockage of STAT3 in hepatocellular carcinoma cells augments NK cell
      functions via reverse hepatocellular carcinoma-induced immune suppression.
AB  - STAT3 is an important transcriptional factor for cell growth, differentiation,
      and apoptosis. Although evidence suggests a positive role for STAT3 in cancer,
      the inhibitory effects of tumor STAT3 on natural killer (NK) cell functions in
      human hepatocellular carcinoma are unclear. In this study, we found that blocking
      STAT3 in hepatocellular carcinoma cells enhanced NK-cell antitumor function. In
      the case of STAT3-blocked hepatocellular carcinoma cells, NKG2D ligands were
      upregulated, which promoted recognition by NK cells. Importantly, the cytokine
      profile of hepatocellular carcinoma cells was altered; in particular, TGF-beta
      and interleukin 10 (IL-10) expression was reduced, and type I interferon (IFN)
      was induced, thus facilitating NK-cell activation. Indeed, the cytotoxicity of NK
      cells treated with supernatant from STAT3-blocked hepatocellular carcinoma cells
      was augmented, with a concomitant elevation of molecules associated with NK
      cytolysis. Further experiments confirmed that the recovery of NK cells depended
      on the downregulation of TGF-beta and upregulation of type I IFN derived from
      STAT3-blocked hepatocellular carcinoma cells. These findings demonstrated a
      pivotal role for STAT3 in hepatocellular carcinoma-mediated NK-cell dysfunction,
      and highlighted the importance of STAT3 blockade for hepatocellular carcinoma
      immunotherapy, which could restore NK-cell cytotoxicity in addition to its direct
      influence on tumor cells.

PMID- 24107451
TI  - Neurotrophic keratitis.
AB  - Neurotrophic keratitis (NK) is a rare degenerative corneal disease that occurs as
      a result of partial or total impairment of trigeminal innervations, leading to a
      reduction (hypoesthesia) in or loss (anaesthesia) of corneal sensitivity. The
      impairment of sensory innervation causes a reduction in the lacrimation reflex
      and the vitality, metabolism and mitosis of epithelial cells, with subsequent
      deficiency in epithelial repair, stromal and intracellular oedema, loss of
      microvilli, and abnormal development of the basal lamina. Several recent studies
      have proposed different therapies based on different aetiopathogenetic theories.
      The aim of the therapy is to treat aetiopathogenesis and, at the same time,
      promote corneal healing. In this paper, we report the aetiology, diagnosis,
      management, and medical and surgical treatment of NK, also indicating future
      treatments based on the most recent studies.

PMID- 24107452
TI  - TFF1 is differentially expressed in stationary and migratory rat gastric
      epithelial cells (RGM-1) after in vitro wounding: influence of TFF1 RNA
      interference on cell migration.
AB  - BACKGROUND/AIMS: The trefoil factor family (TFF) peptide TFF1 is typically
      secreted by gastric surface mucous cells. These cells are also the major players
      in gastric restitution, i.e., repair of the stomach mucosa by cell migration
      after injury. METHODS: An established in vitro model of gastric restitution,
      i.e., migration of the non-transformed rat gastric cell line RGM-1 after scratch
      wounding, was investigated by expression profiling of selected genes from
      separated stationary and migratory cells. Also semi-quantitative
      immunocytochemistry was performed. Furthermore, RGM-1 cells were transfected with
      stealth RNAiTM duplexes targeting Tff1 and relative cell migration rates were
      analyzed. RESULTS: Surprisingly, Tff1 expression was up-regulated in migratory
      cells. No unequivocal signs of the epithelial-mesenchymal transition were
      detectable in migratory cells. Transfection of RGM-1 cells with Tff1-siRNAi
      duplexes negatively influenced migration of these cells. CONCLUSION: This clearly
      points to a function of Tff1 as a motogen. A possible up-regulation of TFF1
      synthesis in migratory surface mucous cells also in vivo would be an ideal
      mechanism to specifically enhance gastric restitution only where topologically
      needed and to minimize eventual negative side effects of TFF1 such as cell
      scattering and invasiveness.

PMID- 24107453
TI  - A 6-week oral gavage toxicity study of a novel galacto-oligosaccharide in
      juvenile rats.
AB  - A novel galacto-oligosaccharide (GOS) was administered by gavage to groups (10
      males and 10 females) of Sprague-Dawley specific pathogen-free rats for 6 weeks
      from day 4 after birth at doses of 0, 500, 1000, or 2000 mg/kg/day. Each pup was
      subjected to a variety of observations to examine for development effects/changes
      after birth: general condition, clinical signs, functional examinations, grip
      strength and spontaneous movement, body weight and feed consumption, external
      differentiation, ophthalmological examination, urinalysis (including water
      consumption), hematology, blood chemistry, necropsy, organ weight, and
      histopathology. During the study period, no deaths occurred in any group and
      there were no observed effects from administration of GOS. Therefore, it was
      concluded that GOS had no effects on the development of animals 4 days after
      birth. Since, there were no abnormalities due to administration of GOS in the
      macroscopic examination, organ weight or histopathology of the reproductive
      organs or differentiation (incisor eruption and eyelid opening) of males or
      females, it was concluded that repeated oral administration of GOS at 2000
      mg/kg/day for 6 weeks from day 4 after birth had : no effects on postnatal
      development. The no observed effect level of GOS by repeated oral administration
      for 6 weeks from day 4 after birth was 2000 mg/kg/day for both males and females
      under the conditions of this study. 

PMID- 24107454
TI  - The effect of melatonin on acetylsalicylic acid-induced kidney and testis damage.
AB  - The aim of this study was to evaluate the acute effect of high-dose
      acetylsalicylic acid (ASA) on kidney and testis, and the potential protective and
      therapeutic effects of melatonin on ASA-related pathology. A total of 40 rats
      were randomly divided into the following 5 groups (n = 8): group 1: control, not
      given any drug; group 2: only 200 mg/kg ASA was given; group 3: 5 mg/kg melatonin
      was given 45 min before administering 200 mg/kg ASA; group 4: 5 mg/kg melatonin
      was given 45 min after administering 200 mg/kg ASA; and group 5: only 5 mg/kg
      melatonin was given. The histopathological changes and the biochemical findings;
      such as malondialdehyde (MDA), superoxide dismutase (SOD), catalase (CAT),
      glutathione peroxidase (GPX), reduced glutathione (GSH), and blood urea nitrogen
      (BUN) as well as serum creatinine (Cr) levels were evaluated. ASA significantly
      increased MDA levels in both kidney and testis, whereas it significantly
      decreased the values of SOD, CAT, GPX, and GSH in kidney and CAT levels in
      testis. Melatonin significantly decreased MDA levels in kidney and ameliorated it
      in testis, whereas it caused elevation in the levels of antioxidants. BUN and Cr
      levels were higher after ASA, whereas these levels were diminished after
      melatonin administration. The improvement obtained by melatonin on ASA-induced
      histological alterations was more prominent when it was used after ASA in kidney
      and before ASA in testis. In this study, we demonstrated the beneficial effect of
      melatonin on high-dose ASA-related pathology of kidney and testis for the first
      time. 

PMID- 24107455
TI  - The effects of vitamin B6 on lens antioxidant system in valproic acid
      administered rats.
AB  - Valproic acid (VPA, 2-propyl pentanoic acid) is a broad-spectrum antiepileptic
      drug (AED) and is commonly used in the treatment of bipolar disorders and
      epilepsy. AEDs are known to result in vascular disturbances. Vitamin B6 (Vit B6)
      is water soluble vitamin essential for normal growth, development, and
      metabolism. In this study, we aimed to investigate the protective effects of Vit
      B6 against VPA-induced lens damage in experimental animals. In this study, male 4
      month-old, Sprague-Dawley rats were used. The animals were divided into four
      groups. Group I was intact control animals. Group II rats were administered with
      Vit B6 (50 mg/kg/day) for 7 days. Group III rats were administered with only VPA
      (500 mg/kg/day) for 7 days. Group IV was given VPA + Vit B6 (in a same dose and
      time). Vit B6 was given to rats by gavage and VPA was given by intraperitoneally.
      On the 8th day of experiment, all of the animals were fasted overnight and then
      killed under ether anesthesia. Lens tissues were taken from animals, homogenized
      in 0.9% saline to make up a 10% homogenate. The homogenates was used for
      glutathione (GSH), lipid peroxidation (LPO), protein levels, and enzyme analysis.
      In VPA groups, levels of lens GSH and LPO and activities of glutathione-S
      transferase, glutathione peroxidase, glutathione reductase, and aldose reductase
      were increased, while superoxide dismutase activity was decreased. Treatment with
      Vit B6 reversed these effects. These results demonstrated that administration of
      Vit B6 is potentially beneficial agent to reduce the lens damage in VPA toxicity,
      probably by decreasing oxidative stress. 

PMID- 24107456
TI  - Diosbulbin B-induced liver injury in mice and its mechanism.
AB  - Dioscorea bulbifera L., a commonly used medicinal plant in China, is reported to
      induce hepatotoxicity. The present study is undertaken to investigate the
      hepatotoxicity induced by diosbulbin B (DB), a diterpene lactone isolated from D.
      bulbifera L., and to further explore its underlying mechanism. DB was
      administered to mice at the doses of 0, 16, 32, and 64 mg/kg once daily for 12
      consecutive days. Liver injury induced by DB was evidenced by the increased
      activity of serum alanine aminotransferase (ALT), aspartate aminotransferase
      (AST), and alkaline phosphatase (ALP). Liver histological evaluation showed that
      the mice treated with DB exhibited liver damage with the swelling of hepatocytes.
      Further results showed that the amount of malondialdehyde (MDA) in the liver was
      increased in mice treated with DB, while the glutathione amount and the enzymatic
      activity of glutathione peroxidase (GPx), glutathione-S-transferase (GST),
      copper/zinc-superoxide dismutase (CuZn-SOD), manganese-SOD (Mn-SOD), and catalase
      (CAT) were all decreased. DB also decreased the gene expression of CuZn-SOD and
      CAT. Taken together, our results indicate that oral administration of DB for 12
      consecutive days can lead to the oxidative stress liver injury in mice. 

PMID- 24107457
TI  - Neuroprotective effect of resveratrol on arsenic trioxide-induced oxidative
      stress in feline brain.
AB  - Arsenic trioxide (As2O3) is a known environmental toxicant and potent
      chemotherapeutic agent. Significant correlation has been reported between arsenic
      exposure (including consumption of arsenic-contaminated water and clinical use of
      As2O3) and dysfunction in the nervous system. In this study, we aimed to
      elucidate the effect of resveratrol with neuroprotective activities on As2O3
      induced oxidative damage and cerebral cortex injury. Twenty-four healthy Chinese
      Dragon Li cats of either sex were randomly divided into four groups: control (1
      ml/kg physiological saline), As2O3 (1 mg/kg), resveratrol (3 mg/kg) and As2O3 (1
      mg/kg) + resveratrol (3 mg/kg). As2O3+resveratrol-treated group were given
      resveratrol (3 mg/kg) 1 h before As2O3 (1 mg/kg) administration. Pretreatment
      with resveratrol upregulated the activities of antioxidant enzymes and attenuated
      As2O3-induced increases in reactive oxygen species and malondialdehyde
      production. In addition, resveratrol attenuated the As2O3-induced reduction in
      the level of reduced glutathione and the ratio of reduced glutathione to oxidised
      glutathione, and accumulation of arsenic in the cerebral cortex. These findings
      support neuroprotective effect of resveratrol on As2O3 toxicity in feline brain
      and provide a better understanding of the mechanism that resveratrol modulates
      As2O3-induced oxidative damage and a stronger rational for clinical use of
      resveratrol to protect brain against the toxicity of arsenic. 

PMID- 24107458
TI  - Nuclear factor erythroid 2-related factor gene variants and susceptibility of
      arsenic-related skin lesions.
AB  - Inorganic arsenic (iAs) is an important pollutant associated with various chronic
      degenerative diseases. The cytoprotective protein nuclear factor erythroid 2
      related factor (NRF2) has been proposed as an important responsive mechanism
      against iAs exposure. The aim of this study was to determine whether the risk of
      skin lesions in people exposed to iAs-contaminated water could be modified by the
      presence of single nucleotide polymorphisms in the NRF2 coding gene. We studied
      117 individuals with long-term iAs exposure and 120 nonexposed individuals. Total
      As was determined in water, meanwhile iAs and its metabolites were measured in
      urine. The iAs-induced skin lesion status was evaluated by expert dermatologists.
      We sequenced the promoter region of NRF2 in a sample of 120 healthy donors. We
      found four polymorphisms previously reported and one novel polymorphism in the 5'
      regulatory region of the NRF2. In this study, we did not find allelic and
      genotype association of NRF2 polymorphisms with iAs-related skin lesion. However,
      the analysis of haplotypes composed by -653GA, and -617CA NRF2 single nucleotide
      polymorphisms showed a significant association with protection against skin
      lesions in the low-As exposure group. This is the first report studying the
      association between NRF2 polymorphisms and susceptibility of As-related skin
      lesions. Increasing the sample size will allow us to confirm this data. 

PMID- 24107459
TI  - Epicardial ablation of ventricular tachycardia in ischemic heart disease.
AB  - BACKGROUND: Epicardial approaches have increased ablation success in nonischemic
      cardiomyopathy, but the use for postinfarction ventricular tachycardias (VT) is
      less clear. We report the findings for epicardial VT ablation in postinfarct
      patients. METHODS AND RESULTS: Records of 444 consecutive patients with VT
      because of prior infarction referred for 600 catheter ablation procedures were
      reviewed. Epicardial procedures were performed in the electrophysiology
      laboratory in 56 (13%) patients using percutaneous (43 patients) or surgical (13
      patients) epicardial access. In 7 patients, epicardial ablation was performed
      surgically in the operating room. In the electrophysiology laboratory epicardial
      VT targets were identified in 38 (68%) patients and epicardial ablation abolished
      >=1 VT in 27 patients (6% of the total study population); inducibility was not
      tested after ablation in 4, and VT remained inducible in 7 patients. No ablation
      was performed in 18 (32%) patients because of no accessible epicardial target or
      a complication. Major complications occurred in 8 (14%) of the 57
      electrophysiology laboratory procedures. After the first procedure any VT
      recurred in 21 (54%) of 39 patients who had epicardial ablation compared with 164
      (47%) of 347 endocardial-only ablation patients (P=0.35). CONCLUSIONS: Epicardial
      ablation is potentially useful in >=6% of the postinfarction VT population, but
      the number could be substantially greater because more than two thirds of
      patients selected for epicardial mapping after failed ablation had an epicardial
      VT target. Successful epicardial ablation of a VT was not predictable from
      infarct location or other patient characteristics.

PMID- 24107460
TI  - Call for discussion about the framework for categorizing economic evaluations of
      health information systems and assessing their quality.

PMID- 24107461
TI  - ADC mapping and T1-weighted signal changes on post-injury MRI predict seizure
      susceptibility after experimental traumatic brain injury.
AB  - OBJECTIVE: Post-traumatic epilepsy (PTE) is a serious complication of traumatic
      brain injury (TBI). This study is designed to determine the feasibility of using
      multiparametric MRI endpoints to predict differences in seizure susceptibility
      after experimental TBI. METHODS: MRI imaging and behavioral measurements were
      performed at multiple time points after lateral fluid percussion injury (FPI) in
      rats. Seizure susceptibility was determined by video-electroencephalogram (EEG)
      monitoring and off-line signal analysis after chemoconvulsant challenge. RESULTS:
      Multiple MRI endpoints, including measures of injury-related brain swelling
      (normalized interhemispheric volume difference, NIVD) and T1-weighted signal
      change with contrast enhancement (a measure of blood-brain barrier disruption,
      BBBD), reliably distinguished between injured and sham-injured animals at 72
      hours after injury. ADC (apparent diffusion coefficient) values (a measure of
      water diffusivity) in injured cortex at 72 hours and 1 week after injury, BBBD in
      injured cortex at 72 hours after injury and NIVD at 72 hours after injury were
      significantly correlated with EEG-based measures of seizure susceptibility to
      chemoconvulsant challenge at 3 months after injury. CONCLUSIONS: The correlations
      between our MRI quantitative endpoints and EEG-based measures of seizure
      susceptibility to chemoconvulsant challenge in injured animals versus sham
      injured animals support the feasibility of these MRI endpoints as potential
      biomarkers for post-traumatic epileptogenesis.

PMID- 24107462
TI  - Burden of illness and quality of life in patients being treated for seasonal
      allergic rhinitis: a cohort survey.
AB  - BACKGROUND: Allergic Rhinitis is an inflammatory disease which is characterised
      by burdensome nasal and/or ocular symptoms. This study aimed to assess the impact
      of symptoms (number of symptom-free days (SFD) and Quality of Life (QoL)) in
      patients with Seasonal Allergic Rhinitis (SAR) being treated with fluticasone
      furoate (FF), mometasone furoate (MF) or fluticasone propionate (FP). METHODS: In
      a cross-sectional, non-interventional, cohort analysis, primary care physicians
      and allergy specialists in France, Germany, and Spain were recruited via
      telephone interviews. Each physician prospectively recruited 4 SAR patients - 2
      receiving FF, 1 receiving MF and 1 receiving FP - during June 2009. Patients
      answered questions on symptoms and completed questionnaires on QoL (mini
      rhinoconjunctivitis Quality of Life Questionnaire, RQLQ) and burden of illness
      (Pittsburgh Sleep Quality Index). RESULTS: A total of 540 patients were recruited
      during June 2009. 88 patients were subsequently found to be ineligible and
      excluded from the analyses. In the 4 weeks prior to assessment, patients reported
      a mean of 14.58 (+/-8.42) SFD. Patients receiving FF had more SFD (mean 15.45 +/
      8.29) than patients receiving MF (adjusted mean difference -1.22, 95% Confidence
      Interval (CI) [-3.16 to 0.72], p=0.434) or FP (adjusted mean difference -1.95,
      95% CI [-3.87 to -0.03], p=0.092), although statistical significance was not
      achieved. The mean RQLQ score was 1.54 (+/-1.06). Patients receiving FF had a
      better quality of life in the previous week (mini-RQLQ score: mean 1.42, +/-1.04)
      than patients receiving MF (adjusted mean difference 0.28, 95% CI [0.03 to 0.52],
      p=0.052) or FP (adjusted mean difference 0.18, 95% CI [-0.05 to 0.41], p=0.244).
      Again, none of these results achieved statistical significance. CONCLUSIONS: At
      the height of the allergy season, patients with SAR suffer symptoms approximately
      50% of the time, and report an impact on their QoL. No significant differences
      were observed between FF, FP and MF related to SFD or QoL. TRIAL REGISTRATION:
      ClinicalTrials.gov identifier: NCT01199757.

PMID- 24107463
TI  - Comparison of oxidative stress status in dogs undergoing laparoscopic and open
      ovariectomy.
AB  - The present study evaluated and compared the oxidative stress status of dogs
      undergoing laparoscopic or open ovariectomy. Twelve healthy female dogs were
      divided into two groups according to the type of the surgical procedure,
      laparoscopic or open ovariectomy. Plasma total oxidant status (TOS), total
      antioxidant status (TAS) and oxidative stress index (OSI) levels for the
      evaluation of oxidative stress were determined. Increases in plasma TOS and OSI
      levels and decreases in TAS levels were observed in both groups after surgery.
      The TOS level was significantly lower in the laparoscopic ovariectomy group
      compared with the open surgery group. Laparoscopic ovariectomy is a safe and
      beneficial surgical alternative to traditional ovariectomy with respect to
      oxidative stress status in dogs.

PMID- 24107464
TI  - Age-related histological changes in kidneys of Brown Norway rat.
AB  - In this study, age-dependent histological changes in the kidneys of Brown Norway
      rat, a strain useful for conducting aging research, were evaluated. Examination
      was performed at 3, 12, 18, 24 and 30 months of age. Sclerotic and hypertrophic
      changes of the glomeruli were observed, and quantitative scores of these changes
      persistently increased with age. A marginal increase in scores was observed for
      glomerular cystic changes and tubulointerstitial damage. Further, urothelial
      hyperplasia was observed in the renal papillae, particularly at 30 months of age.
      In conclusion, the findings of the present study demonstrate that the Brown
      Norway strain exhibits persistent, but mild progression of age-dependent renal
      histological changes.

PMID- 24107465
TI  - Meningoencephalitis caused by Halicephalobus gingivalis in a thoroughbred
      gelding.
AB  - A 6-year-old Thoroughbred gelding was euthanized after a 2-month period of
      abnormal neurological signs, such as circling left in his pen and hitting his
      head and body against the wall. After the horse was euthanized on the farm, a
      half of the brain and whole blood were submitted for diagnostic tests.
      Histopathological examination of the brain revealed granulomatous and
      eosinophilic meningoencephalitis with numerous intralesional nematodes,
      predominantly affecting the cerebrum. Multifocal malacic foci were scattered in
      the brain parenchyma. The intralesional parasites were identified as
      Halicephalobus gingivalis by morphological features and PCR testing. To the best
      of our knowledge, this is the first report of meningoencephalitis caused by H.
      gingivalis in the horse in Korea.

PMID- 24107467
TI  - Development and validation of COMPASS: clinical evidence of orphan medicinal
      products - an assessment tool.
AB  - BACKGROUND: Rare diseases are defined as life-threatening or chronically
      debilitating diseases with a prevalence of 50 out of 100,000 individuals or less.
      Orphan medicinal products (OMPs) are intended for the treatment of rare diseases.
      The assessment of quality of evidence in small populations is often complex. Many
      generic tools are unfit. Therefore, the aim of this study was to develop and
      validate a new tool to assess the quality of OMPs' clinical evidence (COMPASS).
      METHODS: Firstly, a draft version of the COMPASS tool, developed by the authors
      and consisting of three parts, was amended based on suggestions obtained in four
      rounds of expert consultation. Secondly, the tool was put through three rounds of
      validation. The data source was information provided on the Orphanet website and
      in European Public Assessment Report (EPAR) document of the European Medicines
      Agency. RESULTS: The first pilot round revealed a high (92.2%) inter-rater
      agreement for part one of the tool. After further improvements, the final inter
      rater agreement was 86.4% for part two (on methodological quality) and three (on
      quality of reporting) of the tool. The COMPASS tool does not attempt to score or
      rank the quality of clinical evidence, but rather to give an outline of various,
      key elements with respect to quality of clinical evidence of OMP studies.
      CONCLUSIONS: The COMPASS tool can be applied to assess the quality of evidence of
      an OMP based on information in the registration dossier, for example by local
      reimbursement agencies, pharmacists or clinicians. In that way, the tool can
      contribute to making reimbursement and/or treatment decisions increasingly more
      founded on the principles of evidence-based decision making.

PMID- 24107469
TI  - In-gap states of a quantum dot coupled between a normal and a superconducting
      lead.
AB  - We study the in-gap states of a quantum dot hybridized with one conducting and
      another superconducting electrode. The proximity effect suppresses the electronic
      states in the entire subgap regime |omega| < Delta, where Delta denotes the
      energy gap of the superconductor. The Andreev scattering mechanism can induce,
      however, some in-gap states whose line-broadening (inverse life-time) is
      controlled by the hybridization of the quantum dot with the normal electrode. We
      show that the number of such Andreev bound states is substantially dependent on
      the competition between the Coulomb repulsion and the induced on-dot pairing. We
      discuss the signatures of these in-gap states in the tunneling conductance,
      especially in a low-bias regime.

PMID- 24107468
TI  - Detection of serological biomarkers by proximity extension assay for detection of
      colorectal neoplasias in symptomatic individuals.
AB  - BACKGROUND: Although the potential of biomarkers to aid in early detection of
      colorectal cancer (CRC) is recognized and numerous biomarker candidates have been
      reported in the literature, to date only few molecular markers have been approved
      for daily clinical use. METHODS: In order to improve the translation of
      biomarkers from the bench to clinical practice we initiated a biomarker study
      focusing on a novel technique, the proximity extension assay, with multiplexing
      capability and the possible additive effect obtained from biomarker panels. We
      performed a screening of 74 different biomarkers in plasma derived from a case
      control sample set consisting of symptomatic individuals representing CRC
      patients, patients with adenoma, patients with non-neoplastic large bowel
      diseases and healthy individuals. RESULTS: After statistical evaluation we found
      12 significant indicators of CRC and the receiver operating characteristic (ROC)
      curve of Carcinoembryonic antigen (CEA), Transferrin Receptor-1 (TFRC),
      Macrophage migration inhibitory factor (MIF), Osteopontin (OPN/SPP1) and cancer
      antigen 242 (CA242) showed additive effect. This biomarker panel identified CRC
      patients with a sensitivity of 56% at 90% specificity and thus the performance is
      sufficiently high to further investigate this combination of five proteins as
      serological biomarkers for detection of CRC. Furthermore, when applying the
      indicators to identify early-stage CRC a combination of CEA, TFRC and CA242
      resulted in a ROC curve with an area under the curve of 0.861. CONCLUSIONS: Five
      plasma protein biomarkers were found to be potential CRC discriminators and three
      of these were additionally found to be discriminators of early-stage CRC. These
      explorative data in symptomatic individuals demonstrates the feasibility of the
      multiplex proximity extension assay for screening of potential serological
      protein biomarkers and warrants independent analyses in a larger sample cohort,
      including asymptomatic individuals, to further validate the performances of our
      CRC biomarker panel.

PMID- 24107470
TI  - The validity of predicting prognosis by the lymph node ratio in node-positive
      colon cancer.
AB  - BACKGROUND/AIMS: Because the TNM system disregards the number of lymph nodes
      dissected and inter-individual differences exist in the number of regional lymph
      nodes, the lymph node ratio (LNR), which is estimated by dividing the number of
      metastatic lymph nodes by the number of dissected lymph nodes, has been proposed
      as a prognostic factor in recent years. The purpose of the present study is to
      examine the validity of predicting prognosis using the LNR in node-positive colon
      cancer. METHODS: Three hundred and eleven patients with lymph node metastases who
      underwent curative surgery for colon cancer at our department between 1992 and
      2005 were enrolled. Univariate and multivariate analyses were performed to
      evaluate the relationship between clinicopathological factors and prognosis.
      RESULTS: Among the patients with >=12 dissected lymph nodes, differentiation,
      invasion depth and TNM N category were found to be significant independent
      prognostic factors. On the other hand, among the patients with <=11 dissected
      lymph nodes, differentiation and the LNR were found to be significant independent
      prognostic factors. CONCLUSION: Among the patients with <=11 dissected lymph
      nodes, LNR was a significant independent prognostic factor.

PMID- 24107471
TI  - Intramural small vessels in arteriovenous malformations of the heart: a note on
      prognostic significance.

PMID- 24107472
TI  - Health-related quality of life, depression and anxiety correlate with the degree
      of hirsutism.
AB  - BACKGROUND: Hirsutism has a negative impact on women's quality of life. The
      relation between quality of life, anxiety, depression and the level of hairiness
      has not been described. AIMS: To investigate the correlations between the levels
      of hairiness, quality of life, anxiety and depression. METHODS: 200 patients from
      Malmo, Orebro and Uppsala, who had been in contact with the clinics for problems
      with excessive hair growth, were invited to answer a self-administered
      questionnaire including sociodemographic questions, EQ-5D index score,
      Dermatology Life Quality Index (DLQI), Hospital Anxiety and Depression Scale
      (HADS) and Ferriman-Gallwey scale (F-G); of these, 127 women participated in the
      study. RESULTS: The mean values were: EQ-5D index 0.73 (SD = 0.27), EQ visual
      analogue scale 61.0 (SD = 22.6), HADS-anxiety 9.5 +/- 5.3 and HADS-depression 6.5
      +/- 4.6. The mean DLQI was 11.8 +/- 8.4, indicating a very large effect on
      patients' lives. All were significantly correlated with the amount of hairiness.
      CONCLUSIONS: Higher levels of hair growth were significantly correlated with a
      lower level of quality of life and symptoms of both anxiety and depression.

PMID- 24107474
TI  - Randomised trial of volume-targeted ventilation versus pressure-limited
      ventilation in acute respiratory failure in prematurely born infants.
AB  - BACKGROUND: During volume-targeted ventilation (VTV), a constant volume is
      delivered with each ventilator inflation. OBJECTIVES: To determine whether VTV
      compared to pressure-limited ventilation (PLV) reduced the time to reach weaning
      criteria in prematurely born infants with acute respiratory distress, and if any
      difference was explained by better respiratory muscle strength and/or a lower
      work of breathing (WOB). METHODS: Infants of <34 weeks of gestational age
      ventilated for <24 h in the first week after birth were randomised to receive
      either VTV or PLV. The primary outcome was the time to achieve pre-specified
      weaning criteria. Respiratory muscle strength was assessed by the measurement of
      the maximum inflation and expiratory pressures, and the WOB assessed by the
      transdiaphragmatic pressure time product. Other outcomes reported are the
      duration of ventilation, occurrence of patent ductus arteriosus, pneumothorax,
      intraventricular haemorrhage, periventricular leukomalacia and episodes of
      hypocarbia. RESULTS: Forty infants, median gestational age 27 (range 23-33)
      weeks, were recruited. The time taken to achieve weaning criteria was similar in
      the two groups [median 14 h (VTV) vs. 23 h (PLV)]. There were no significant
      differences between the groups with regard to respiratory muscle strength, WOB or
      other outcomes, except that fewer of the VTV compared to the PLV group had
      episodes of hypocarbia (8 vs. 19; p < 0.001). CONCLUSION: In prematurely born
      infants with acute respiratory failure, use of VTV did not reduce the time to
      reach weaning criteria, but was associated with a reduction in episodes of
      hypocarbia.

PMID- 24107473
TI  - "Pre-schoolers in the playground" an outdoor physical activity intervention for
      children aged 18 months to 4 years old: study protocol for a pilot cluster
      randomised controlled trial.
AB  - BACKGROUND: The pre-school years are considered critical for establishing healthy
      lifestyle behaviours such as physical activity. Levels of physical activity track
      through childhood into adulthood, thus establishing habitual physical activity
      early in life is vital. Time spent outdoors is associated with greater physical
      activity and playground interventions have been shown to increase physical
      activity in school aged children. There are few pre-school, playground-based
      interventions, and evaluations of these have found mixed results. A recent report
      published by the UK Chief Medical Officer (CMO) highlighted that new
      interventions to promote movement in the early years (0-5 years old) are needed.
      The aim of this study is to undertake a pilot cluster randomised controlled trial
      (RCT) of an outdoor playground-based physical activity intervention for parents
      and their children aged 18 months to 4 years old ("Pre-schoolers in the
      Playground"; PiP) and to assess the feasibility of conducting a full scale
      cluster RCT. The PiP intervention is grounded in behavioural theory (Social
      Cognitive Theory), and is in accordance with the CMO guidance for physical
      activity in the early years. It is informed by existing literature and data
      collected from focus groups with parents. METHODS/DESIGN: One hundred and fifty
      pre-school children affiliated to 10 primary schools will be recruited. Schools
      will be randomised to either the PiP intervention arm or the control arm (usual
      practice). Children in the intervention arm will be invited to attend three 30
      minute outdoor play sessions per week for 30 weeks (3 school terms) at the
      school. Feasibility will be assessed by examining recruitment rates, attendance,
      attrition, acceptability of the trial and of the PiP intervention to parents,
      fidelity of intervention implementation, capability and capacity for schools to
      deliver the intervention. Health outcomes and the feasibility of outcome
      measurement tools will be assessed. These include physical activity via triaxial,
      accelerometry (Actigraph GT3X+), anthropometry (height, body mass, BMI, waist and
      upper arm circumference), health related quality of life for child (PedsQL) and
      parent (EQ5D), parent wellbeing (ComQol-A5), injuries and health service use. A
      health economic evaluation will also be undertaken. DISCUSSION: It is anticipated
      that results of this pilot trial will be published in spring 2015. TRIAL
      REGISTRATION: Current controlled trials: ISRCTN54165860.

PMID- 24107475
TI  - Chromosome evolution in dendropsophini (Amphibia, Anura, Hylinae).
AB  - Dendropsophini is the most species-rich tribe within Hylidae with 234 described
      species. Although cytogenetic information is sparse, chromosome numbers and
      morphology have been considered as an important character system for systematic
      inferences in this group. Using a diversity of standard and molecular techniques,
      we describe the previously unknown karyotypes of the genera Xenohyla, Scarthyla
      and Sphaenorhynchus and provide new information on Dendropsophus and Lysapsus.
      Our results reveal significant karyotype diversity among Dendropsophini, with
      diploid chromosome numbers ranging from 2n = 22 in S. goinorum, 2n = 24 in
      Lysapsus, Scinax, Xenohyla, and almost all species of Sphaenorhynchus and
      Pseudis, 2n = 26 in S. carneus, 2n = 28 in P. cardosoi, to 2n = 30 in all known
      Dendropsophus species. Although nucleolar organizer regions (NORs) and C-banding
      patterns show a high degree of variability, NOR positions in 2n = 22, 24 and 28
      karyotypes and C-banding patterns in Lysapsus and Pseudis are informative
      cytological markers. Interstitial telomeric sequences reveal a diploid number
      reduction from 24 to 22 in Scarthyla by a chromosome fusion event. The diploid
      number of X. truncata corroborates the character state of 2n = 30 as a
      synapomorphy of Dendropsophus.

PMID- 24107476
TI  - Factors that determine and limit the resistivity of high-quality individual ZnO
      nanowires.
AB  - Knowing and controlling the resistivity of an individual nanowire (NW) is crucial
      for the production of new sensors and devices. For ZnO NWs this is poorly
      understood; a 10(8) variation in resistivity has previously been reported, making
      the production of reproducible devices almost impossible. Here, we provide
      accurate resistivity measurements of individual NWs, using a four-probe scanning
      tunnelling microscope (STM), revealing a dependence on the NW dimensions. To
      correctly interpret this behaviour, an atomic level transmission electron
      microscopy technique was employed to study the structural properties of the NWs
      in relation to three growth techniques: hydrothermal, catalytic and non-catalytic
      vapour phase. All NWs were found to be defect free and structurally equivalent;
      those grown with a metallic catalyst were free from Au contamination. The
      resistivity measurements showed a distinct increase with decreasing NW diameter,
      independent of growth technique. The increasing resistivity at small NW diameters
      was attributed to the dominance of surface states removing electrons from the
      bulk. However, a fundamental variance in resistivity (10(2)) was observed and
      attributed to changes in occupied surface state density, an effect which is not
      seen with other NW materials such as Si. This is examined by a model to predict
      the effect of surface state occupancy on the measured resistivity and is
      confirmed with measurements after passivating the ZnO surface. Our results
      provide an understanding of the primary influence of the reactive nature of the
      surface and its dramatic effect on the electrical properties of ZnO NWs. 

PMID- 24107477
TI  - Study of VSX1 mutations in patients with keratoconus in southwest Iran using PCR
      single-strand conformation polymorphism/heteroduplex analysis and sequencing
      method.
AB  - OBJECTIVE: Keratoconus (KC) is an eye disorder in which the cornea is swollen,
      thinned and deformed. Despite extensive studies, the pathophysiological processes
      and genetic etiology of KC are unknown. The disease incidence is approximately 1
      in 2,000, and it is the most common cause of corneal transplantation in the USA.
      Many genes are involved in the disease, but evidence suggests a major role for
      VSX1 in the etiology of KC. This study aimed to determine the frequency of
      mutations in exons 2, 3 and 4 of the VSX1 gene in Chaharmahal va Bakhtiari
      province in the southwest of Iran. STUDY DESIGN: In this experimental study,
      mutations in 3 exons, namely exons 2, 3 and 4, of VSX1 were investigated in 50
      patients with KC and 50 healthy control subjects. DNA was extracted using a
      standard phenol-chloroform method. PCR-single-strand conformational
      polymorphism/heteroduplex analysis was performed, followed by DNA sequencing to
      confirm the identified motility shifts. RESULTS: H244R mutations were found in 1
      patient and also in 1 healthy control subject. Furthermore, 12 polymorphisms were
      identified in patients with KC and 7 in healthy control subjects [rs6138482 and
      c.546A>G (rs12480307)]. CONCLUSION: Our investigation showed that KC-related VSX1
      mutations were found in a very small proportion of the studied patients from
      Iran. Further investigations on other genes are needed to clarify their roles in
      KC pathogenesis.

PMID- 24107478
TI  - An analysis of registered clinical trials in otolaryngology from 2007 to 2010:
      ClinicalTrials.gov.
AB  - OBJECTIVE: To describe the conditions studied, interventions used, study
      characteristics, and funding sources of otolaryngology clinical trials from the
      ClinicalTrials.gov database; compare this otolaryngology cohort of interventional
      studies to clinical visits in a health care system; and assess agreement between
      clinical trials and clinical activity. STUDY DESIGN: Database analysis. SETTING:
      Trial registration data downloaded from ClinicalTrials.gov and administrative
      data from the Duke University Medical Center from October 1, 2007 to September
      27, 2010. METHODS: Data extraction from ClinicalTrials.gov was done using MeSH
      and non-MeSH disease condition terms. Studies were subcategorized to create the
      following groupings for descriptive analysis: ear, nose, allergy, voice, sleep,
      head and neck cancer, thyroid, and throat. Duke Health System visits were queried
      by using selected ICD-9 codes for otolaryngology and non-otolaryngology
      providers. Visits were grouped similarly to ClinicalTrials.gov for further
      analysis. Chi-square tests were used to explore differences between groups.
      RESULTS: A total of 1115 of 40,970 registered interventional trials were assigned
      to otolaryngology. Head and neck cancer trials predominated. Study models most
      frequently incorporated parallel design (54.6%), 2 study groups (46.6%), and
      randomization (69.1%). Phase 2 or 3 studies constituted 46.4% of the cohort.
      Comparison of the ClinicalTrials.gov database with administrative health system
      visit data by disease condition showed discordance between national research
      activity and clinical visit volume for patients with otolaryngology complaints.
      CONCLUSIONS: Analysis of otolaryngology-related clinical research as listed in
      ClinicalTrials.gov can inform patients, physicians, and policy makers about
      research focus areas. The relative burden of otolaryngology-associated conditions
      in our tertiary health system exceeds research activity within the field.

PMID- 24107479
TI  - Early postoperative results in stapedectomy.
AB  - OBJECTIVE: To measure early audiometric changes after primary stapedotomy. STUDY
      DESIGN: Case series with chart review. SETTING: Academic inner-city hospitals.
      SUBJECTS AND METHODS: Consecutive patients operated on by the first author were
      included (only 1 ear in cases of bilateral surgery), and their audiometric
      results were reviewed. Data were analyzed from 45 ears. Air and bone audiometric
      measures were analyzed from 5 days post operation and 6 months post operation.
      Threshold shifts were quantified at 5 days and 6 months post operation. RESULTS:
      Overall results for the group were good, with 91% of patients achieving an air
      bone gap less than or equal to 10 dB by 6 months post operation. Threshold shifts
      in at least 1 frequency were common at 5 days (62% of patients), but less so at 6
      months (36%). Patients with shifts did not have worse overall outcomes at 6
      months than those with no shifts. No difference in results was observed for the 2
      prostheses used in this series. CONCLUSION: Early audiometric results after
      stapedectomy commonly reveal worsened bone conduction (postoperative threshold
      shifts), which may reflect cochlear trauma, but do not lead to poorer outcomes as
      measured by conventional methods.

PMID- 24107480
TI  - Spindle cell melanoma: a comparison of the cytomorphological features with the
      epithelioid variant.
AB  - OBJECTIVES: Fine-needle aspiration cytology serves as a rapid and cost-effective
      tool for the diagnosis of melanoma, especially in the recurrent and metastatic
      cases. The diagnosis poses a challenge due to the varied morphological patterns.
      Spindle cell melanoma mimics other sarcomas and carcinomas on morphology. This
      study highlights the cytomorphological features of spindle cell melanoma and
      compares them with the conventional epithelioid type. STUDY DESIGN: Cytology
      smears of 55 aspirates from 45 diagnosed cases of melanoma from various sites
      were reviewed. Histopathology correlation was done in spindle and mixed cell
      tumors. RESULTS: Melanomas with a pure or mixed spindle cell component occurred
      in 31% of the cases and in a slightly higher age group. These demonstrated
      prominent cellular cohesion (p < 0.0001), mild to moderate nuclear atypia and
      inconspicuous to small nucleoli as compared to the epithelioid variant. The
      presence of melanin pigment was a useful clue to the diagnosis. Most of the cases
      correlated well with the histomorphology. CONCLUSION: Spindle cell melanoma is a
      morphological variant which can be readily misinterpreted due to a lack of
      classical cytological features of melanoma. Hence, these are vulnerable to be
      misinterpreted as other neoplasms. An awareness of clinical and cytological
      features is important to reach the correct diagnosis.

PMID- 24107481
TI  - Phase II trial of biweekly chemotherapy with docetaxel and cisplatin in high-risk
      patients with unresectable non-small cell lung cancer.
AB  - PURPOSE: We investigated the efficacy and toxicity of a biweekly schedule of
      docetaxel and cisplatin in high-risk patients with unresectable (stages IIIB-IV)
      non-small cell lung cancer (NSCLC). METHODS: In this study, 48 high-risk patients
      with previously untreated locally advanced or metastatic NSCLC were treated with
      combination chemotherapy consisting of docetaxel 40 mg/m(2) and cisplatin 40
      mg/m(2); both drugs were given biweekly, on days 1 and 15, every 4 weeks in an
      outpatient setting. RESULTS: Complete response, partial response, and stable
      disease were observed in 1 (2.1%), 30 [62.5%, 95% confidence interval (CI) 47.9
      77.1], and 4 (8.3%) patients. The median overall survival was 15.1 months (95% CI
      11.7-18.5) and the median time to progression was 7.5 months (95% CI 6.4-8.6).
      The major toxicity was grade 3 anemia in 7 (14.6%) patients. Grade 3/4
      neutropenia was observed in 5 (10.4%) patients. Among the nonhematologic
      toxicities, grade 3 infection and grade 3 diarrhea were observed in 5 (10.4%) and
      4 (8.3%) patients, respectively. No treatment-related mortality was found.
      CONCLUSIONS: As a front-line chemotherapy for high-risk patients with
      unresectable NSCLC in an outpatient setting, the biweekly schedule of docetaxel
      and cisplatin showed feasible efficacy with acceptable hematologic toxicities,
      comparable to the results of previous studies of triweekly or weekly schedules.
      Additional large randomized studies are needed to optimize the schedule and
      dosage of combination therapy with docetaxel and cisplatin in high-risk patients
      with unresectable NSCLC.

PMID- 24107482
TI  - Electrophysiological characterisation of motor and sensory tracts in patients
      with hereditary spastic paraplegia (HSP).
AB  - BACKGROUND: Hereditary spastic paraplegias (HSPs) are characterised by lower limb
      spasticity due to degeneration of the corticospinal tract. We set out for an
      electrophysiological characterisation of motor and sensory tracts in patients
      with HSP. METHODS: We clinically and electrophysiologically examined a cohort of
      128 patients with genetically confirmed or clinically probable HSP. Motor evoked
      potentials (MEPs) to arms and legs, somato-sensory evoked potentials of median
      and tibial nerves, and nerve conduction studies of tibial, ulnar, sural, and
      radial nerves were assessed. RESULTS: Whereas all patients showed clinical signs
      of spastic paraparesis, MEPs were normal in 27% of patients and revealed a broad
      spectrum with axonal or demyelinating features in the others. This heterogeneity
      can at least in part be explained by different underlying genotypes, hinting for
      distinct pathomechanisms in HSP subtypes. In the largest subgroup, SPG4, an
      axonal type of damage was evident. Comprehensive electrophysiological testing
      disclosed a more widespread affection of long fibre tracts involving peripheral
      nerves and the sensory system in 40%, respectively. Electrophysiological
      abnormalities correlated with the severity of clinical symptoms. CONCLUSIONS:
      Whereas HSP is primarily considered as an upper motoneuron disorder, our data
      suggest a more widespread affection of motor and sensory tracts in the central
      and peripheral nervous system as a common finding in HSP. The distribution
      patterns of electrophysiological abnormalities were associated with distinct HSP
      genotypes and could reflect different underlying pathomechanisms.
      Electrophysiological measures are independent of symptomatic treatment and may
      therefore serve as a reliable biomarker in upcoming HSP trials.

PMID- 24107483
TI  - Expression of VPAC1 in a murine model of allergic asthma.
AB  - Vasoactive intestinal polypeptide (VIP) is a putative neurotransmitter of the
      inhibitory non-adrenergic non-cholinergic nervous system and influences the
      mammalian airway function in various ways. Hence known for bronchodilatory,
      immunomodulatory and mucus secretion modulating effects by interacting with the
      VIP receptors VPAC1 and VPAC2, it is discussed to be a promising target for
      pharmaceutical intervention in common diseases such as COPD and bronchial asthma.
      Here we examined the expression and transcriptional regulation of VPAC1 in the
      lungs of allergic mice using an ovalbumin (OVA) -induced model of allergic
      asthma. Mice were sensitized to OVA and challenged with an OVA aerosol. In
      parallel a control group was sham sensitized with saline. VPAC1 expression was
      examined using RT-PCR and real time-PCR studies were performed to quantify gene
      transcription. VPAC1 mRNA expression was detected in all samples of OVA
      sensitized and challenged animals and control tissues. Further realtime analysis
      did not show significant differences at the transcriptional level.Although the
      present studies did not indicate a major transcriptional regulation of VPAC1 in
      states of allergic airway inflammation, immunomodulatory effects of VPAC1 might
      still be present due to regulations at the translational level. 

PMID- 24107484
TI  - Family history of premature coronary heart disease, child cardio-metabolic risk
      factors and left ventricular mass.
AB  - In a prospective cohort of 181 individuals followed up since childhood--when aged
      9, 12 and 15 years--patients with a family history of premature coronary heart
      disease (n=18) had higher left ventricular mass index in adulthood--at mean age
      of 31 years--compared with those without (mean+/-standard error 39.1+/-1.9 versus
      34.6+/-0.7 g/m(2.7), p=0.04). The correlation between adult left ventricular mass
      index and child triglycerides (r=0.66, p=0.04 versus r=-0.03, p=0.75;
      p(diff)=0.02) and diastolic blood pressure (r=0.65, p=0.02 versus r=0.16, p=0.07;
      p(diff)=0.05) was stronger among those with a family history of coronary heart
      disease than in those without. Although preliminary, these data suggest that the
      higher left ventricular mass index among adults with a family history might be
      explained by their increased susceptibility to child cardio-metabolic risk
      factors.

PMID- 24107485
TI  - Triple versus dual antiplatelet therapy in acute coronary syndromes: adding
      cilostazol to aspirin and clopidogrel?
AB  - Dual antiplatelet therapy (DAPT) with aspirin and a P2Y12 receptor antagonist is
      the standard of care in acute coronary syndromes. Additionally, novel P2Y12
      receptor antagonists such as prasugrel and ticagrelor are even recommended over
      clopidogrel in certain clinical guidelines. Despite the fact that clopidogrel is
      fraught with significant variability in on-treatment platelet reactivity, the
      novel P2Y12 receptor antagonists come at the price of increased side effects and
      cost. Therefore, alternative or supplementary antiplatelet therapies are needed.
      Cilostazol, a phosphodiesterase III inhibitor, has been shown to significantly
      improve high on-treatment platelet reactivity in patients receiving both aspirin
      and clopidogrel and has antiproliferative effects (inhibiting neointimal
      hyperplasia and smooth muscle proliferation), thus reducing the risk of
      restenosis after coronary stent implantation. Further, cilostazol in addition to
      aspirin and clopidogrel versus DAPT in patients undergoing percutaneous coronary
      intervention showed that triple antiplatelet therapy (TAPT) was associated with a
      significantly greater platelet inhibition, reduced major adverse cardiovascular
      events, target lesion revascularization, and target vessel revascularization with
      no increased risk for a hemorrhagic event. Moving forward, larger randomized
      controlled trials are required comparing TAPT versus DAPT (clopidogrel, prasugrel
      or ticagrelor on top of aspirin).

PMID- 24107486
TI  - An epidemiological study of Hypoderma infection and control using ivermectin in
      yaks in Qinghai Province, China.
AB  - The prevalence of Hypoderma spp. in yaks grazed in the east of Qinghai province
      was investigated in 2008. In this area, the prevalence in young yaks (1- to 3
      year-old) was very high at 82.2-98.7%, whilst in adult yaks (4-year-old and
      older), the prevalence was 42.4-50.6%. The seasonal development and migration
      pattern of Hypoderma larvae in yak bodies was found to be similar for different
      locations in this area. The numbers of first, second and third instar larvae
      detected in yak bodies peaked in October, December and March, respectively.
      Different doses of ivermectin (125 to 500 ug/kg body weight) almost completely
      dewormed the larvae from yaks, suggesting that using a quarter of the prescribed
      dose (500 ug/kg body weight) was effective. In October of each year between 2009
      and 2012, ivermectin (125 ug/kg body weight) was administered to a total of
      562,995 yaks grazed in four counties in Qinghai province, and the pevalence of
      Hypoderma larval infection in yaks was reduced to 0.5-1.0%.

PMID- 24107487
TI  - Characterization of a UDP-N-acetylglucosamine biosynthetic pathway encoded by the
      giant DNA virus Mimivirus.
AB  - Mimivirus is a giant DNA virus belonging to the Megaviridae family and infecting
      unicellular Eukaryotes of the genus Acanthamoeba. The viral particles are
      characterized by heavily glycosylated surface fibers. Several experiments suggest
      that Mimivirus and other related viruses encode an autonomous glycosylation
      system, forming viral glycoproteins independently of their host. In this study,
      we have characterized three Mimivirus proteins involved in the de novo uridine
      diphosphate-N-acetylglucosamine (UDP-GlcNAc) production: a glutamine-fructose-6
      phosphate transaminase (CDS L619), a glucosamine-6-phosphate N-acetyltransferase
      (CDS L316) and a UDP-GlcNAc pyrophosphorylase (CDS R689). Sequence and enzymatic
      analyses have revealed some unique features of the viral pathway. While it
      follows the eukaryotic-like strategy, it also shares some properties of the
      prokaryotic pathway. Phylogenetic analyses revealed that the Megaviridae enzymes
      cluster in monophyletic groups, indicating that they share common ancestors, but
      did not support the hypothesis of recent acquisitions from one of the known
      hosts. Rather, viral clades branched at deep nodes in phylogenetic trees, forming
      independent clades outside sequenced cellular organisms. The intermediate
      properties between the eukaryotic and prokaryotic pathways, the phylogenetic
      analyses and the fact that these enzymes are shared between most of the known
      members of the Megaviridae family altogether suggest that the viral pathway has
      an ancient origin, resulting from lateral transfers of cellular genes early in
      the Megaviridae evolution, or from vertical inheritance from a more complex
      cellular ancestor (reductive evolution hypothesis). The identification of a virus
      encoded UDP-GlcNAc pathway reinforces the concept that GlcNAc is a ubiquitous
      sugar representing a universal and fundamental process in all organisms. 

PMID- 24107488
TI  - Comprehensive analysis on clinical features of Wilson's disease: an experience
      over 28 years with 133 cases.
AB  - OBJECTIVES: Here, we reported our experience over 28 years with 133 cases of
      patients with Wilson's disease (WD) in order to illustrate the diverse clinical
      presentation and to improve understanding and early diagnosis of WD. METHODS: We
      reviewed the medical records of patients with WD at Shengjing Hospital of China
      Medical University from 1993 to 2011. The clinical manifestations and laboratory
      findings were analyzed. The diagnosis was based on the presence of Kayser
      Fleisher (K-F) rings, low serum copper levels, low serum ceruloplasmin levels,
      increased urinary copper concentrations before or after penicillamine challenge.
      RESULTS: Among them, 93 patients mainly presented with hepatic manifestations, 27
      with neural abnormalities, and 13 presented with others. Age range at diagnosis
      was wide (3-74 years, average 13.2 years), and five patients were over 40 years.
      The oldest one was aged 74 years and presented with neuropsychiatric disorder.
      The positive rate of K-F rings was 93.0%. The serum ceruloplasmin decreased in
      83.6% patients, 24-hour urinary copper increased in 88.1% patients, and serum
      copper decreased in 68.9% patients. About 79.7% of patients were diagnosed within
      6 months, but only 33.1% were diagnosed at their initial medical consultation.
      There was a substantial delay of up to 15 years. CONCLUSIONS: The clinical
      manifestation of WD is very diverse and no one feature is completely reliable.
      Doctors in many fields have opportunities to encounter this disease, and the most
      important thing is to be aware of the possibility of WD.

PMID- 24107489
TI  - Adipose-derived regenerative cell (ADRC)-enriched fat grafting: optimal cell
      concentration and effects on grafted fat characteristics.
AB  - BACKGROUND: To overcome the absorption of traditional fat grafting, techniques
      for adipose-derived regenerative cell (ADRC)-enriched fat grafting are currently
      being adapted for practical application. The Celution800/CRS (Cytori
      Therapeutics, San Diego, CA) has enabled rapid grafting of the patient's own
      freshly harvested ADRCs without requiring a culturing step. However, the optimal
      cell concentration and the effects of ADRCs on the characteristics of grafted fat
      after free fat grafting remain unclear. METHODS: ADRCs were isolated and purified
      from human fat tissue using the Celution800/CRS. Animals that received fat
      grafting without the addition of ADRCs were designated the control group (group
      A). The number of ADRCs per grafted fat volume (mL) was adjusted to 3 * 105, 1.5
      * 106, and 3 * 106 cells/mL (groups B, C, and D, respectively), mixed with free
      fat, and transplanted as ADRC-enriched fat grafting. These mixtures were
      transplanted subcutaneously into BALB/C Jcl-nu/nu mice. The volume of grafted fat
      was determined 5 months after transplantation, and histological assessments were
      performed. RESULTS: ADRC-enriched fat grafting resulted in decreased fat
      absorption and the formation of greater numbers of new blood vessels in the
      grafted fat. The optimal ADRC concentration in this study was found to be 3 * 105
      cells/mL (group B), with higher concentrations resulting in increased cyst and
      fibril formation in the grafted fat. CONCLUSIONS: This study used the
      Celution800/CRS for free fat grafting and demonstrated that the concentration of
      transplanted ADRCs affected the engraftment and quality of the grafted fat.

PMID- 24107490
TI  - A preliminary genetic map in Solea senegalensis (Pleuronectiformes, Soleidae)
      using BAC-FISH and next-generation sequencing.
AB  - This article presents the first physical mapping carried out in the Senegalese
      sole (Solea senegalensis), an important marine fish species of Southern Europe.
      Eight probes were designated to pick up genes of interest in aquaculture
      (candidate genes) from a bacterial artificial chromosome (BAC) library using a
      method of rapid screening based on a 4-dimension PCR. Seven known and 3 unknown
      clones were isolated and labeled. The 10 BAC clones were used as probes to map
      the karyotype of the species by fluorescence in situ hybridization (FISH). Nine
      out of the 10 clones were localized in only 1 chromosome pair, whereas the
      remaining one hybridized on 2 chromosome pairs. The 2-color FISH experiments
      showed colocation of 4 probes in 2 chromosome pairs. In addition, 2-color FISH
      was carried out both with 5S rDNA and the BAC containing the lysozyme gene
      published previously. This first genetic map of the Senegalese sole represents a
      starting point for future studies of the sole genome. In addition, 7 out of the
      10 BAC clones were sequenced using next-generation sequencing, and bioinformatic
      characterization of the sequences was carried out. Hence the anchoring of the
      sequences to specific chromosomes or chromosome arms is now possible, leading to
      an initial scaffold of the Senegalese sole genome.

PMID- 24107491
TI  - Positron emission tomography/computed tomographic and magnetic resonance imaging
      in a murine model of progressive atherosclerosis using (64)Cu-labeled
      glycoprotein VI-Fc.
AB  - BACKGROUND: Plaque erosion leads to exposure of subendothelial collagen, which
      may be targeted by glycoprotein VI (GPVI). We aimed to detect plaque erosion
      using (64)Cu-labeled GPVI-Fc (fragment crystallized). METHODS AND RESULTS: Four
      week-old male apolipoprotein E-deficient (ApoE(-/-)) mice (n=6) were fed a high
      fat diet for 12 weeks. C57BL/6J wild-type (WT) mice served as controls (n=6).
      Another group of WT mice received a ligation injury of the left carotid artery
      (n=6) or sham procedure (n=4). All mice received a total activity of ~12 MBq
      (64)Cu-GPVI-Fc by tail vein injection followed by delayed (24 hours) positron
      emission tomography using a NanoPET/computed tomographic scanner (Mediso,
      Hungary; Bioscan, USA) with an acquisition time of 1800 seconds. Seventy-two
      hours after positron emission tomography/computed tomography, all mice were
      scanned 2 hours after intravenous administration of 0.2 mmol/kg body weight of a
      gadolinium-based elastin-specific MR contrast agent. MRI was performed on a 3-T
      clinical scanner (Philips Healthcare, Best, The Netherlands). In ApoE(-/-) mice,
      the (64)Cu-GPVI-Fc uptake in the aortic arch was significantly higher compared
      with WT mice (ApoE(-/-): 13.2+/-1.5 Bq/cm(3) versus WT mice: 5.1+/-0.5 Bq/cm(3);
      P=0.028). (64)Cu-GPVI-Fc uptake was also higher in the injured left carotid
      artery wall compared with the intact right carotid artery of WT mice and as a
      trend compared with sham procedure (injured: 20.7+/-1.3 Bq/cm(3) versus intact:
      2.3+/-0.5 Bq/cm(3); P=0.028 versus sham: 12.7+/-1.7 Bq/cm(3); P=0.068). Results
      were confirmed by ex vivo histology and in vivo MRI with elastin-specific MR
      contrast agent that measures plaque burden and vessel wall remodeling. Higher R1
      relaxation rates were found in the injured carotid wall with a T1 mapping
      sequence (injured: 1.44+/-0.08 s(-1) versus intact: 0.91+/-0.02 s(-1); P=0.028
      versus sham: 0.97+/-0.05 s(-1); P=0.068) and in the aortic arch of ApoE(-/-) mice
      compared with WT mice (ApoE(-/-): 1.49+/-0.05 s(-1) versus WT: 0.92+/-0.04 s(-1);
      P=0.028). CONCLUSIONS: (64)Cu-GPVI-Fc positron emission tomographic imaging
      allows identification of exposed subendothelial collagen in injured WT and high
      fat diet-fed ApoE(-/-) mice.

PMID- 24107492
TI  - Arginine and asthma.
AB  - Recent studies suggest that alterations of the arginine metabolome and a
      dysregulation of nitric oxide (NO) homeostasis play a role in the pathogenesis of
      asthma. L-Arginine, a semi-essential amino acid, is a common substrate for both
      the arginases and NO synthase (NOS) enzyme families. NO is an important
      vasodilator of the bronchial circulation, with both bronchodilatory and anti
      inflammatory properties, and is synthesized from oxidation of its obligate
      substrate L-arginine, which is catalyzed by a family of NOS enzymes. Arginase is
      an essential enzyme in the urea cycle, responsible for the conversion of arginine
      to ornithine and urea. The NOS and arginase enzymes can be expressed
      simultaneously under a wide variety of inflammatory conditions, resulting in
      competition for their common substrate. Although much attention has been directed
      towards measurements of exhaled NO in asthma, accumulating data show that low
      bioavailability of L-arginine also contributes to inflammation,
      hyperresponsiveness and remodeling of the asthmatic airway. Aberrant arginine
      catabolism represents a novel asthma paradigm that involves excess arginase
      activity, elevated levels of asymmetric dimethyl arginine, altered intracellular
      arginine transport, and NOS dysfunction. Addressing the alterations in arginine
      metabolism may result in new strategies for treatment of asthma.

PMID- 24107493
TI  - Changes in arginine metabolism during sepsis and critical illness in children.
AB  - Arginine is an important amino acid during disease and healing because of
      functions in the immune system and as precursor of nitric oxide (NO). In
      critically ill adults and children, plasma arginine and citrulline concentrations
      are substantially decreased, indicating an arginine-deficient state. Arginine
      availability is reduced because of increased arginine disposal in combination
      with reduced de novo arginine synthesis. The latter is most likely caused by
      reduced citrulline availability. As a result, NO synthesis may be impaired, which
      might compromise microcirculation. These metabolic changes seem to be dependent
      on the severity of inflammation. Arginine or citrulline supplementation in severe
      inflammation might therefore be beneficial. Possibly, the use of protein-energy
      enriched formulas may be a first step to improve arginine availability and NO
      synthesis. In critically ill children, arginine metabolism and supplementation is
      however a virtually unexplored field. Since pediatric sepsis is a significant
      health problem, which differs in epidemiology and pathophysiology from sepsis in
      adults, and because of the scarcity of data in this population, studies focused
      on pathophysiological mechanisms and possible interventions in arginine
      metabolism in pediatric critical illness are warranted.

PMID- 24107494
TI  - Arginine deficiency caused by myeloid cells: importance, identification and
      treatment.
AB  - Dietary arginine supplementation has been suggested as a means of improving T
      lymphocyte function and has found its greatest clinical utility in patients
      undergoing elective surgery. In other illnesses, arginine supplementation is
      controversial. Breakthroughs in understanding arginine metabolism have led to the
      identification of myeloid cells that express arginase 1, causing significant
      depletion of arginine - an essential amino acid for normal T lymphocyte function.
      Hence, myeloid cells expressing arginase 1 are also known as myeloid-derived
      suppressor cells. This chapter discusses the hypothesis that arginine replacement
      therapy may be necessary in arginine deficiency states.

PMID- 24107495
TI  - Glutamine supplementation in neonates: is there a future?
AB  - Over the past couple of decades, glutamine (GLN) has emerged as important
      metabolic intermediate, signaling molecule and nutrient that becomes rapidly
      depleted and therefore critically important during stress. In very low
      birthweight (VLBW) infants, a population of patients in whom supplementation of
      GLN should provide major benefits, GLN is provided in subnutritional quantities
      because standard parenteral nutrition solutions do not contain GLN and most of
      these babies do not receive full enteral feedings until several weeks after
      birth. No evidence of toxicity of GLN supplementation was found in these clinical
      trials, but the results for efficacy on a limited number of outcomes have been
      mixed. The use of GLN supplementation in VLBW infants has therefore not become
      routine. Some authors suggest that further study in this area is no longer
      warranted. The purpose of this review is to provide an update in the area of GLN
      supplementation for preterm infants in order to determine whether GLN
      supplementation is unwarranted and/or additional investigations are needed.
      Evidence is presented and an argument is made that thoughtful reevaluation of
      future applications and trials of GLN in premature infants is warranted.

PMID- 24107496
TI  - Insulin in human milk and the use of hormones in infant formulas.
AB  - Human milk contains a substantial number of hormones and growth factors. Studies
      in animal models show that some of these peptides (e.g. insulin, insulin-like
      growth factor 1, IGF-1, epidermal growth factors) have an effect on the small
      intestine after orogastric administration. Recently, two efforts were made to
      incorporate growth factors into infant formulas. One of these efforts included
      the incorporation of IGF-1, and the second is an ongoing effort to evaluate the
      safety and efficacy of incorporating insulin into infant formulas. The rational
      and current evidence for adding insulin to infant formulas (presence in human
      milk, effects of orally administrated insulin on gut maturation, intestinal
      permeability, systemic effects and preliminary encouraging results of
      supplementing insulin to a preterm infant formula) is detailed in this review. If
      the addition of insulin to preterm infant formulas indeed results in better
      growth and accelerated intestinal maturation, future studies will need to address
      the supplementation of insulin in term infants and assess the efficacy of such
      supplementation in enhancing gut maturation and prevention of later
      noncommunicable diseases such as allergy, autoimmune diseases and obesity.

PMID- 24107497
TI  - Diet, gut enterotypes and health: is there a link?
AB  - The human gut contains a vast number of microorganisms known collectively as the
      'gut microbiota'. Despite its importance in maintaining the health of the host,
      growing evidence suggests the gut microbiota may also be an important factor in
      the pathogenesis of various diseases, a number of which have shown a rapid
      increase in incidence over the past few decades. Factors including age, genetics,
      and diet may influence microbiota composition. We used diet inventories and 16S
      rDNA sequencing to characterize fecal samples from 98 individuals. Fecal
      communities clustered into previously described enterotypes were distinguished
      primarily by levels of Bacteroides and Prevotella. Enterotypes were associated
      with long-term diets, particularly protein and animal fat (Bacteroides) versus
      simple carbohydrates (Prevotella). Although the distinction of enterotypes as
      either discrete clusters or a continuum will require additional investigation,
      numerous studies have demonstrated the coexclusion of the closely related
      Prevotella and Bacteroides genera in the gut microbiota in healthy human
      subjects, where Prevotella appears to be a discriminatory taxon for residence in
      more agrarian societies. Ultimately, the impact of diet on the human gut
      microbiota may be an important environmental factor involved in the pathogenesis
      of disease states that show a rapidly increasing incidence in industrialized
      nations.

PMID- 24107498
TI  - Understanding immunomodulatory effects of probiotics.
AB  - The intestinal microbiota is known to be a driving force in the development and
      maintenance of the immune system. While substantial shifts in the microbiota
      composition may influence immune functionality in a longer term, short occasional
      changes might also be sensed. The latter opens considerable perspectives for the
      use of nutritional interventions, intended to modulate immune functionality in a
      desired direction. Probiotics are discussed here as a possible way to achieve
      this goal. It seems that effects are not only strain specific, but will depend on
      many environmental factors that make the immune system receptive or not to the
      influences of a given probiotic strain. The interactions between probiotics on
      the one hand and enterocytes or immune cells on the other hand, are a complex
      interplay that is rarely mediated by a single mechanism. Immunomodulation through
      nutrition is therefore a complex phenomenon that needs careful consideration,
      understanding of immune functionality as well as insight into the mechanisms of
      probiotic activities. Only then can the proper clinical trials with proper
      readouts be set up to prove efficacy of each strain/mixture individually.

PMID- 24107499
TI  - Transforming growth factor and intestinal inflammation: the role of nutrition.
AB  - The intestinal mucosa possesses a complex epithelial barrier and a well-organized
      local immune system, which both efficiently protect this internal-external
      surface against potential microbial aggressions while guaranteeing tolerance
      towards harmless bacteria or antigens (oral tolerance). There is good
      experimental evidence that the intestinal microbiota is a main driver for the
      development of the mucosal immune system. Any perturbations/changes of this
      interaction with the intestinal microbiota or the microbial colonization process
      may cause health problems with short- and eventually long-term consequences, such
      as suspected for allergic or dysimmune disorders. Dendritic cells (DC) play a key
      role in the initiation of immune responses. Immune responses elicited by
      intestinal DC differ markedly from those initiated by spleen-derived DC: while
      intestinal DC induce anti-inflammatory and tolerogenic responses to harmless
      antigens such as derived from the resident microflora or harmless food allergens,
      systemic immune activation yields in a strong inflammatory TH1/TH17 reaction to
      the same antigens. The recent discovery how DC functions are regulated and
      imprinted by the microenvironment (DC conditioning) will be discussed in this
      review. High concentrations of retinoic acid or vitamin D metabolites, thymic
      stromal lymphopoietin and/or transforming growth factor-beta (TGF-beta) activate
      signaling programs in DC that yield in priming of regulatory and anti
      inflammatory T cell responses. TGF-beta is one of the key factors implicated in
      intestinal immune regulation; it is produced by a large variety of cells in the
      intestinal mucosa, including intestinal epithelial cells, lymphocytes and
      monocytes/macrophages/DC. An important anti-inflammatory effect of TGF-beta on
      the immune system is the promotion and generation of FOXP3-positive regulatory T
      cells in the intestinal compartment. There are first and encouraging data from
      the treatment of Crohn's disease, an inflammatory GI condition, that targeted
      enteral therapy with optimized concentrations of immunoregulatory peptides, such
      as TGF-beta, might of interest for the treatment of inflammatory disorders.

PMID- 24107500
TI  - Microbiota modulation: can probiotics prevent/treat disease in pediatrics?
AB  - A number of metagenomic analyses providing knowledge of the human microbiome have
      yielded data on the differences between healthy and diseased individuals.
      Microbiota manipulation, such as through the administration of probiotics, may
      potentially contribute to improved health outcomes. The objective of this review
      was to summarize the most recent data on the use of probiotics to treat or
      prevent diseases in pediatrics. MEDLINE and The Cochrane Database of Systematic
      Reviews were searched in September 2012 for randomized controlled trials or their
      meta-analyses published in the last 3 years. To provide examples of current
      research interests, the focus of the search was on well-studied, common pediatric
      conditions as well as on some chronic diseases for which the benefits of gut
      microbiota manipulation are only in the early stages.

PMID- 24107501
TI  - Membrane composition and cellular responses to fatty acid intakes and factors
      explaining the variation in response.
AB  - The lipid membrane bilayer undergoes continuous changes, and its lipid
      composition is both adaptive and highly varied, with substantial molecular
      variety. The balance of dietary fats, namely saturated versus unsaturated, and
      polyunsaturated fatty acids (PUFA) of the n-6 series versus those of the n-3
      series, may change membrane composition thus affecting membrane order,
      intracellular signaling processes, and gene expression. As a consequence, changes
      in the production of both lipid and peptide mediators influencing the individual
      adaptive responses take place. More than that of all the other fatty acids, the n
      3 PUFA composition of cell membranes depends on their dietary intake. n-3 PUFA
      levels in cell membranes are related to both inflammatory and immune diseases,
      possibly by downregulating the expression of genes involved in their synthesis
      and maybe the pathogenesis of processes associated with the disease itself. The
      interindividual variability of DNA sequences involved in the synthesis of long
      chain PUFA may explain differences in responses to their dietary contribution in
      regulating the risk of disease. Lifestyle factors (such as smoking and alcohol
      consumption) may in turn negatively impact PUFA metabolism. Accordingly,
      different amounts of dietary PUFA may be necessary to meet the requirements for
      these nutrients in development and disease prevention on an individual basis.

PMID- 24107502
TI  - Docosahexaenoic acid and its derivative neuroprotectin D1 display neuroprotective
      properties in the retina, brain and central nervous system.
AB  - The significance of the selective enrichment in omega-3 essential fatty acids
      (docosahexaenoyl - DHA - chains of membrane phospholipids, 22C and 6 double
      bonds) in the nervous system (e.g. synaptic membranes and dendrites) has
      remained, until recently, incompletely understood. While studying mechanisms of
      neuronal survival, we contributed to the discovery of a docosanoid synthesized by
      15-lipoxygenase-1 from DHA, which we dubbed neuroprotectin D1 (NPD1;10R,17S
      dihydroxy-docosa-4Z,7Z,11E,13E,15E,19Z hexaenoic acid). NPD1 is a docosanoid
      because it is derived from a 22C precursor (DHA), unlike eicosanoids, which are
      derived from the 20C arachidonic acid family of essential fatty acids not
      enriched in the nervous system. We found that NPD1 is promptly made in response
      to oxidative stress, seizures and brain ischemia-reperfusion. NPD1 is
      neuroprotective in experimental brain damage, retinal pigment epithelial cells,
      and in human brain cells. Thus, NPD1 acts as a protective sentinel, one of the
      very first defenses activated when cell homeostasis is threatened by
      neurodegenerations. NPD1 also has been shown to have a specificity and potency
      that provides beneficial bioactivity during initiation and early progression of
      neuronal and retinal degenerations, epilepsy and stroke. In short, NPD1
      regulation promotes homeostatic regulation of neural circuitry integrity.

PMID- 24107503
TI  - Branched-chain fatty acids in the neonatal gut and estimated dietary intake in
      infancy and adulthood.
AB  - Branched-chain fatty acids (BCFA) are primarily saturated fatty acids (FA) with a
      methyl branch, usually near the terminal methyl group. BCFA are abundant in
      bacteria, skin, and vernix caseosa but have seldom been studied with respect to
      human nutrition. They are constituents of the term newborn infant gut lumen,
      being swallowed as vernix particulate components of amniotic fluid in the last
      trimester of normal pregnancy. We recently showed that BCFA protect against
      necrotizing enterocolitis (NEC) in the rat pup model. Dietary BCFA at levels
      similar to those found in human vernix reduced NEC incidence by more than 50%,
      increased the abundance of BCFA-containing bacteria, and increased the expression
      of ileal anti-inflammatory IL-10. The few published reports of BCFA in human milk
      enable an estimate that breastfed infants consume 19 mg BCFA per 100 ml milk.
      Dietary BCFA consumption from milk fat and other ruminant products, the main
      sources of dietary BCFA, is more than 400 mg BCFA per day in adult Americans.
      This estimate exceeds by severalfold the average dietary intake of bioactive FA,
      such as docosahexaenoic acid. BCFA are bioactive, abundant but neglected
      components of the human food supply.

PMID- 24107504
TI  - Clinical overview of effects of dietary long-chain polyunsaturated fatty acids
      during the perinatal period.
AB  - The current report provides a brief background introducing 30 years of research
      on long-chain polyunsaturated fatty acids (LC-PUFA) and infant development, but
      focuses mainly on challenges for future studies. Infants fed formulas containing
      only vegetable fats were found to have lower docosahexaenoic acid (DHA, 22:6n-3)
      and arachidonic acid (20:4n-6) status than infants fed human milk. Studies soon
      focused on efforts to improve LC-PUFA status and evaluate functions suggested by
      early primate studies of DHA deficiency. Despite evidence for the importance of
      these fatty acids for development, particularly DHA, several recent meta-analyses
      conclude dietary supplementation does not enhance development. Future studies
      should employ (1) more finely grained measures of brain development as opposed to
      global measures, and (2) tests that evaluate development later in childhood when
      children are able to be tested on more complex behaviors (if found effective
      these would also be evidence of early brain programming). (3) Studies are needed
      to understand the cause of high variability in transfer of DHA to the fetus. (4)
      Finally, the role of single-nucleotide polymorphisms of the fatty acid desaturase
      genes 1 and 2 of mother and infant needs study to determine how they affect
      requirements for these fatty acids by the fetus/infant.

PMID- 24107505
TI  - Dietary n-3 LC-PUFA during the perinatal period as a strategy to minimize
      childhood allergic disease.
AB  - There has been growing interest in the role of n-3 long-chain polyunsaturated
      fatty acids (LC-PUFA) in the modulation of the immune response during early
      childhood and whether this may translate to a reduction in childhood allergic
      disease. Several randomized controlled trials of n-3 LC-PUFA supplementation have
      been reported, largely involving children who are at high hereditary risk of
      developing allergies. These studies relatively consistently indicate that
      supplementation during pregnancy results in fewer children with atopic eczema in
      early childhood. On the other hand, supplementation studies confined exclusively
      to the postnatal period have demonstrated mixed results with one trial showing no
      effect and the other suggesting a transient effect on symptoms of respiratory
      disease. In summary, supplementation with n-3 LC-PUFA during the perinatal period
      and before allergic response is established may be a useful strategy to prevent
      early childhood allergic disease in children at high hereditary risk. Further
      work is needed to establish the optimal period of supplementation and whether
      longer term benefits exist.

PMID- 24107506
TI  - Concluding remarks.

PMID- 24107508
TI  - Methods of haemostasis during liver resection--a UK national survey.
AB  - BACKGROUND: Although haemorrhage is a major cause of morbidity and mortality in
      liver surgery, there is very little available guidance on its management.
      METHODS: The aim of this study was to identify current practice in the UK in this
      regard. An online survey was created and hepatobiliary (HPB) specialists who were
      members of a specialist society and others who were known practitioners were
      invited by e-mail to complete the survey anonymously. RESULTS: Fifty-one percent
      responded (n = 36/70), and most of these respondents worked at large HPB centres
      (>100 liver resections/year; n = 24, 66%). Not all questionnaires were fully
      completed by the individual surgeons. Thirty-eight percent of the surgeons
      routinely used Pringle's manoeuvre. Most surgeons used ligation of the inflow
      vessels (n = 16, 44%) and stapled the outflow vessels (n = 15, 42%). The Cavitron
      ultrasonic surgical aspirator (CUSA; 54%, 13/24) was preferred for parenchymal
      transection. The majority routinely used haemostatic adjuncts (n = 22, 62%),
      whilst 33% (n = 12) used them occasionally. Twenty-three (64%) felt manufactured
      haemostatic adjuncts played a major role in maintaining haemostasis and 19
      preferred fibrin-based products. CONCLUSION: The Pringle manoeuvre is a popular
      technique amongst specialist UK liver surgeons and the CUSA is used by nearly
      half of the surgeons. Despite the absence of definitive evidence for their
      benefit, manufactured haemostatic adjuncts are still widely used, especially the
      fibrin-based adjuncts.

PMID- 24107510
TI  - Tissue effects resulting from eraser laser enucleation of the prostate: in vivo
      investigation.
AB  - BACKGROUND/AIMS/OBJECTIVES: To describe the depth of the laser coagulation zone
      in vivo based on histological examinations and the functional outcome of a 1,318
      nm diode laser for enucleation in benign prostatic enlargement (BPE). METHODS: A
      total of 20 patients with BPE were treated by laser Eraser(r) enucleation of the
      prostate (ELEP). Prostatic tissue wedges were evaluated to assess the depth of
      the ELEP coagulation zones. Additionally, patients were assessed preoperatively
      and 12 months postoperatively. RESULTS: The coagulation zones were 0.36 +/- 0.17
      mm in epithelial tissue, 0.28 +/- 0.15 mm in stromal tissue, and 0.25 +/- 0.12 mm
      in mixed tissue. The coagulation area at the cutting edge completely sealed
      capillary vessels, reaching a depth of 0.35 +/- 0.15 mm. The diameter of the
      coagulated vessels measured 1.75 +/- 0.83 mm. Mean blood loss was 115.54 +/-
      93.12 ml, catheter time 1.35 +/- 0.33 days, and hospital stay 1.89 +/- 0.52 days.
      The International Prostate Symptom Score, maximal flow rate, and quality of life
      significantly improved 12 months after the procedure. CONCLUSIONS: ELEP is safe
      and effective for BPE treatment and yields good results at a follow-up of 1 year.
      Because of the limited penetration depth, damage to the urinary sphincter is not
      expected.

PMID- 24107511
TI  - Lubrication of Stone-Wales transformations in graphene by hydrogen and hydroxyl
      functional groups.
AB  - First-principles calculations were performed to address the role of functional
      groups (hydrogen atoms and hydroxyl molecules) in lubricating the fundamental
      transformation by which a Stone-Wales defect is formed in graphene. Energy
      barriers in the presence of a single H atom, as well as in the case of two, four,
      and six H atoms chemisorbed in graphene in several distinct site configurations
      are found to be smaller than in pristine graphene. Our study examines in detail
      the electronic mechanism behind the stabilization, by the functional groups, of
      the transition state of the defect-forming reaction relative to the reactants
      (functionalized graphene and Stone-Wales defect), due to partial strain
      relaxation and electronic saturation of the transition-state dangling bonds. We
      frame these findings in terms of the reactivity, to the functional groups, of the
      reactants and transition states. Our calculations point to a very favorable
      kinetic pathway with a strongly reduced activation barrier, in which two H atoms
      bind to next-nearest-neighbor C atoms, and saturate the two transition-state
      dangling bonds, resulting in a strong barrier reduction of 5.6 eV (from 9.3 eV
      without functional groups to 3.7 eV). In the case of two chemisorbed OH
      molecules, we find a further reduction of the Stone-Wales transformation barrier
      for one configuration considered, when compared to the similar one with two H
      atoms, providing additional confirmation of the reactivity-based mechanism.

PMID- 24107509
TI  - The GNAS complex locus and human diseases associated with loss-of-function
      mutations or epimutations within this imprinted gene.
AB  - GNAS is a complex imprinted locus leading to several different gene products that
      show exclusive monoallelic expression. GNAS also encodes the alpha-subunit of the
      stimulatory G protein (Gsalpha), a ubiquitously expressed signaling protein that
      is essential for the actions of many hormones and other endogenous molecules.
      Gsalpha is expressed biallelically in most tissues but its expression is silenced
      from the paternal allele in a small number of tissues. The tissue-specific
      paternal silencing of Gsalpha results in different parent-of-origin-specific
      phenotypes in patients who carry inactivating GNAS mutations. In this paper, we
      review the GNAS complex locus and discuss how disruption of Gsalpha expression
      and the expression of other GNAS products shape the phenotypes of human disorders
      caused by mutations in this gene.

PMID- 24107513
TI  - Peroxisome proliferator-activated receptor-gamma agonist pioglitazone suppresses
      experimental autoimmune uveitis.
AB  - Peroxisome proliferator-activated receptor (PPAR)-gamma agonists are clinically
      used as anti-diabetes agents. Recent research has discovered that an anti
      inflammatory effect of PPAR agonist may have the potential to treat autoimmune
      disease. In the present study, we investigated the anti-inflammatory effects of
      PPAR-gamma agonist, pioglitazone, on murine model of endogenous uveitis.
      Experimental autoimmune uveoretinitis (EAU) was induced by immunizing C57BL/6
      mice with human interphotoreceptor retinoid binding protein-derived peptide (1
      20). Pioglitazone or vehicle was injected intravenously from day -1 (whole phase
      treatment) or day 8 (effector phase study) until day 20. Severity of EAU was
      assessed clinically and pathologically on day 21. Immunological status was
      assessed by measuring intraocular inflammatory factors, and activation and
      regulatory markers of CD4(+) T cells in draining lymph nodes (LNs). Treatment
      with pioglitazone suppressed both whole-phase and effector-phase of EAU. In
      effector-phase treatment, intraocular concentrations of TNF-alpha and IL-6 were
      significantly suppressed, and CD4(+)Foxp3(+) regulatory T cells and
      CD4(+)CD62L(high) naive T cells increased in draining LNs, although there were no
      differences in CD4(+)CD44(high) effector T cells and IL-17 producing CD4(+) T
      cells between pioglitazone- and vehicle-treated mice. Administration of
      pioglitazone before and after the onset of EAU significantly reduced disease
      severity. The present results suggest that pioglitazone may be a novel
      therapeutic agent for endogenous uveitis. 

PMID- 24107512
TI  - The alpha4 nicotinic receptor promotes CD4+ T-cell proliferation and a helper T
      cell immune response.
AB  - Smoking is a common addiction and a leading cause of disease. Chronic nicotine
      exposure is known to activate nicotinic acetylcholine receptors (nAChRs) in
      immune cells. We demonstrate a novel role for alpha4 nAChRs in the effect of
      nicotine on T-cell proliferation and immunity. Using cell-based sorting and
      proteomic analysis we define an alpha4 nAChR expressing helper T-cell population
      (alpha4(+)CD3(+)CD4(+)) and show that this group of cells is responsive to
      sustained nicotine exposure. In the circulation, spleen, bone marrow, and thymus,
      we find that nicotine promotes an increase in CD3(+)CD4(+) cells via its
      activation of the alpha4 nAChR and regulation of G protein subunit o, G protein
      regulated-inducer of neurite outgrowth, and CDC42 signaling within T cells. In
      particular, nicotine is found to promote a helper T cell 2 adaptive immunologic
      response within T cells that is absent in alpha4(-/-) mice. We thus present a new
      mechanism of alpha4 nAChR signaling and immune regulation in T cells, possibly
      accounting for the effect of smoking on the immune system. 

PMID- 24107514
TI  - High-mobility group box protein-1 released by human-periodontal ligament cells
      modulates macrophage migration and activity in vitro.
AB  - Recent studies have demonstrated the interplay of human periodontal ligament
      cells (hPDLs) with immune cells, such as macrophages, during tissue repair. High
      mobility group box protein-1 (HMGB1) is released into the extracellular milieu by
      damaged cells and functions as an alarmin to mediate the inflammatory host
      response. The present study addressed the role of HMGB1 released by hPDLs in the
      regulation of macrophage differentiation, migration and activity. The aim was to
      examine the inflammatory potential of HMGB1 itself and in combination with other
      mediators. The induction of sterile necrosis by thermal insult of hPDLs resulted
      in HMGB1 translocation from the nucleus to the cytoplasm and on to the
      extracellular space, as determined by immunocytochemistry/ELISA. Exposure of
      human macrophages to the conditioned PDL cell medium increased the expression of
      macrophage differentiation/activation markers CD14, CD23, CD64 and CD163.
      Chemotactic migration and osteoclastic differentiation of macrophages were also
      enhanced. Supplementation of the conditioned medium with a saturating
      concentration of HMGB1-Ab reduced these effects. Challenge with recombinant HMGB1
      protein induced less migration and osteoclast differentiation than thermal
      insult. These data point to the immune modulatory capacity of hPDLs by the
      release of mediators, including HMGB1, which modify macrophage differentiation,
      migration and activity during periodontal repair, and indicate an enhanced HMGB1
      activity when acting in concert with other mediators. 

PMID- 24107516
TI  - Hybrid functionals for solids with an optimized Hartree-Fock mixing parameter.
AB  - (Screened) hybrid functionals are being used more and more for solid-state
      calculations. Usually the fraction alpha of Hartree-Fock exchange is kept fixed
      during the calculation; however, there is no single (universal) value for alpha
      which systematically leads to satisfying accuracy. Instead, one could use a
      property of the system under consideration to determine alpha, and in this way
      the functional would be more flexible and potentially more accurate. Recently, it
      was proposed to use the static dielectric constant epsilon for the calculation of
      alpha (Shimazaki and Asai 2008 Chem. Phys. Lett. 466 91 and Marques et al 2011
      Phys. Rev. B 83 035119). We explore this idea further and propose a scheme where
      the connection between epsilon and alpha is optimized based on experimental band
      gaps. epsilon, and thus alpha, is recalculated at each iteration of the self
      consistent procedure. We present results for the bandgap and lattice constant of
      various semiconductors and insulators with this procedure. In addition, we show
      that this approach can also be combined with a non-self-consistent hybrid
      approximation to speed up the calculations considerably, while retaining an
      excellent accuracy in most cases.

PMID- 24107517
TI  - [Research activities on hormonal agents - focusing on kisspeptin and reproductive
      functions].

PMID- 24107515
TI  - Identification of single nucleotide polymorphisms in hematopoietic cell
      transplant patients affecting early recognition of, and response to, endotoxin.
AB  - Hematopoietic cell transplant (HCT) is a life-saving therapy for many malignant
      and non-malignant bone marrow diseases. Associated morbidities are often due to
      transplant-related toxicities and infections, exacerbated by regimen-induced
      immune suppression and systemic incursion of bacterial products. Patients
      undergoing myeloablative conditioning for HCT become endotoxemic and display
      blood/plasma changes consistent with lipopolysaccharide (LPS)-induced systemic
      innate immune activation. Herein, we addressed whether patients scheduled for HCT
      display differences in recognition/response to LPS ex vivo traceable to specific
      single nucleotide polymorphisms (SNPs). Two SNPs of LPS binding protein (LBP)
      were associated with changes in plasma LBP levels, with one LBP SNP also
      associating with differences in efficiency of extraction and transfer of
      endotoxin to myeloid differentiation factor-2 (MD-2), a step needed for
      activation of TLR4. None of the examined SNPs of CD14, bactericidal/permeability
      increasing protein (BPI), TLR4 or MD-2 were associated with corresponding protein
      plasma levels or endotoxin delivery to MD-2, but CD14 and BPI SNPs significantly
      associated with differences in LPS-induced TNF-alpha release ex vivo and
      infection frequency, respectively. These findings suggest that specific LBP, CD14
      and BPI SNPs might be contributory assessments in studies where clinical outcome
      may be affected by host response to endotoxin and bacterial infection. 

PMID- 24107518
TI  - [Current development status and prospect of dual PI3K/mTOR inhibitors for cancer
      therapy].

PMID- 24107519
TI  - [Preclinical biomarker research and patient stratification of molecular target
      agents: the anti-angiogenic inhibitor Lenvatinib mesylate (E7080)].

PMID- 24107520
TI  - [Development of an anti-CCR4 antibody, mogamulizumab, the first approved antibody
      made by POTELLIGENT((r)) technology].

PMID- 24107521
TI  - [Cellular and molecular mechanisms in drug-induced nephrotoxicity and its
      prevention].

PMID- 24107522
TI  - [Imaging glutamate spillover in the brain].

PMID- 24107523
TI  - [Open innovation for Japanese pharmaceutical companies].

PMID- 24107524
TI  - [New therapeutic choice for COPD: glycopyrronium bromide, a long-acting
      muscarinic antagonist].

PMID- 24107525
TI  - [Diabetes and cognitive impairment].

PMID- 24107526
TI  - [Regulation of mitochondrial dynamism. Fragile-handle with care].

PMID- 24107527
TI  - Pregnancy-associated plasma protein-A as a marker of culprit lesion instability
      in unstable angina patients: an intravascular ultrasound study.
AB  - BACKGROUND: We evaluated the relationship between pregnancy-associated plasma
      protein-A (PAPP-A) and coronary plaque instability as assessed by intravascular
      ultrasound (IVUS). METHODS: We performed greyscale IVUS analysis in culprit
      lesions of 93 patients with unstable angina (UA) and 72 with stable angina (SA).
      A sandwich enzyme-linked immunosorbent assay technique was used to assay
      circulating PAPP-A. RESULTS: Patients with UA had higher PAPP-A levels than those
      with SA 10.8 mIU/l [interquartile range (IQR) 8.3-14.4] vs. 5.4 (IQR 2.9-9.8)
      mIU/l, p < 0.001]. Lesions in patients with higher PAPP-A levels were associated
      with larger plaque burden than lesions in patients with lower PAPP-A levels. IVUS
      attenuated plaque, positive remodeling and plaque rupture. Thrombus and
      angiographic Ambrose type-II eccentric lesions or multiple irregularities were
      more common in patients with higher PAPP-A levels than in those with lower PAPP-A
      levels. They were also more common in patients with UA and higher PAPP-A levels
      than in patients with (1) SA and higher PAPP-A levels, (2) UA and lower PAPP-A
      levels or (3) SA and lower PAPP-A levels. CONCLUSIONS: Higher PAPP-A levels were
      associated with coronary plaque instability in vivo and unstable symptoms in
      patients with coronary artery disease.

PMID- 24107528
TI  - Nocturnal hypothermia impairs flight ability in birds: a cost of being cool.
AB  - Many birds use regulated drops in night-time body temperature (Tb) to conserve
      energy critical to winter survival. However, a significant degree of hypothermia
      may limit a bird's ability to respond to predatory attack. Despite this likely
      energy-predation trade-off, the behavioural costs of avian hypothermia have yet
      to be examined. We thus monitored the nocturnal hypothermia of mourning doves
      (Zenaida macroura) in a laboratory setting in response to food deprivation.
      Nocturnal flight tests were used to quantify the flight ability of hypothermic
      doves. Many hypothermic doves (39% of tests) could not fly while carrying a small
      weight, but could do so after quickly warming up to typical daytime Tb. Doves
      that were unable to fly during their first test were more hypothermic than those
      that could fly, with average Tb reductions of 5.3 degrees C and 3.3 degrees C,
      respectively, but there was no overall indication of a threshold Tb reduction
      beyond which doves were consistently incapable of flight. These results suggest
      that energy-saving hypothermia interferes with avian antipredator behaviour via a
      reduction in flight ability, likely leading to a trade-off between energy-saving
      hypothermia and the risk of predation. 

PMID- 24107529
TI  - Global warming triggers the loss of a key Arctic refugium.
AB  - We document the rapid transformation of one of the Earth's last remaining Arctic
      refugia, a change that is being driven by global warming. In stark contrast to
      the amplified warming observed throughout much of the Arctic, the Hudson Bay
      Lowlands (HBL) of subarctic Canada has maintained cool temperatures, largely due
      to the counteracting effects of persistent sea ice. However, since the mid-1990s,
      climate of the HBL has passed a tipping point, the pace and magnitude of which is
      exceptional even by Arctic standards, exceeding the range of regional long-term
      variability. Using high-resolution, palaeolimnological records of algal remains
      in dated lake sediment cores, we report that, within this short period of intense
      warming, striking biological changes have occurred in the region's freshwater
      ecosystems. The delayed and intense warming in this remote region provides a
      natural observatory for testing ecosystem resilience under a rapidly changing
      climate, in the absence of direct anthropogenic influences. The environmental
      repercussions of this climate change are of global significance, influencing the
      huge store of carbon in the region's extensive peatlands, the world's southern
      most polar bear population that depends upon Hudson Bay sea ice and permafrost
      for survival, and native communities who rely on this landscape for sustenance. 

PMID- 24107530
TI  - Conceptual learning by miniature brains.
AB  - Concepts act as a cornerstone of human cognition. Humans and non-human primates
      learn conceptual relationships such as 'same', 'different', 'larger than',
      'better than', among others. In all cases, the relationships have to be encoded
      by the brain independently of the physical nature of objects linked by the
      relation. Consequently, concepts are associated with high levels of cognitive
      sophistication and are not expected in an insect brain. Yet, various works have
      shown that the miniature brain of honeybees rapidly learns conceptual
      relationships involving visual stimuli. Concepts such as 'same', 'different',
      'above/below of' or 'left/right are well mastered by bees. We review here
      evidence about concept learning in honeybees and discuss both its potential
      adaptive advantage and its possible neural substrates. The results reviewed here
      challenge the traditional view attributing supremacy to larger brains when it
      comes to the elaboration of concepts and have wide implications for understanding
      how brains can form conceptual relations. 

PMID- 24107531
TI  - Divergent selection on, but no genetic conflict over, female and male timing and
      rate of reproduction in a human population.
AB  - The sexes often have different phenotypic optima for important life-history
      traits, and because of a largely shared genome this can lead to a conflict over
      trait expression. In mammals, the obligate costs of reproduction are higher for
      females, making reproductive timing and rate especially liable to conflict
      between the sexes. While studies from wild vertebrates support such sexual
      conflict, it remains unexplored in humans. We used a pedigreed human population
      from preindustrial Finland to estimate sexual conflict over age at first and last
      reproduction, reproductive lifespan and reproductive rate. We found that the
      phenotypic selection gradients differed between the sexes. We next established
      significant heritabilities in both sexes for all traits. All traits, except
      reproductive rate, showed strongly positive intersexual genetic correlations and
      were strongly genetically correlated with fitness in both sexes. Moreover, the
      genetic correlations with fitness were almost identical in men and women. For
      reproductive rate, the intersexual correlation and the correlation with fitness
      were weaker but again similar between the sexes. Thus, in this population, an
      apparent sexual conflict at the phenotypic level did not reflect an underlying
      genetic conflict over the studied reproductive traits. These findings emphasize
      the need for incorporating genetic perspectives into studies of human life
      history evolution. 

PMID- 24107532
TI  - Grazers: biocatalysts of terrestrial silica cycling.
AB  - Silica is well known for its role as inducible defence mechanism countering
      herbivore attack, mainly through precipitation of opaline, biogenic silica (BSi)
      bodies (phytoliths) in plant epidermal tissues. Even though grazing strongly
      interacts with other element cycles, its impact on terrestrial silica cycling has
      never been thoroughly considered. Here, BSi content of ingested grass, hay and
      faeces of large herbivores was quantified by performing multiple chemical
      extraction procedures for BSi, allowing the assessment of chemical reactivity.
      Dissolution experiments with grass and faeces were carried out to measure direct
      availability of BSi for dissolution. Average BSi and readily soluble silica
      numbers were higher in faeces as compared with grass or hay, and differences
      between herbivores could be related to distinct digestive strategies. Reactivity
      and dissolvability of BSi increases after digestion, mainly due to degradation of
      organic matrices, resulting in higher silica turnover rates and mobilization
      potential from terrestrial to aquatic ecosystems in non-grazed versus grazed
      pasture systems (2 versus 20 kg Si ha(-1) y(-1)). Our results suggest a crucial
      yet currently unexplored role of herbivores in determining silica export from
      land to ocean, where its availability is linked to eutrophication events and
      carbon sequestration through C-Si diatom interactions. 

PMID- 24107534
TI  - What, where and when: deconstructing memory.
AB  - The ability of animals to remember the what, where and when of a unique past
      event is used as an animal equivalent to human episodic memory. We currently view
      episodic memory as reconstructive, with an event being remembered in the context
      in which it took place. Importantly, this means that the components of a what,
      where, when memory task should be dissociable (e.g. what would be remembered to a
      different degree than when). We tested this hypothesis by training hummingbirds
      to a memory task, where the location of a reward was specified according to
      colour (what), location (where), and order and time of day (when). Although
      hummingbirds remembered these three pieces of information together more often
      than expected, there was a hierarchy as to how they were remembered. When seemed
      to be the hardest to remember, while errors relating to what were more easily
      corrected. Furthermore, when appears to have been encoded as a combination of
      time of day and sequence information. As hummingbirds solved this task using
      reconstruction of different memory components (what, where and when), we suggest
      that similar deconstructive approaches may offer a useful way to compare episodic
      and episodic-like memories. 

PMID- 24107533
TI  - Diversity of functional microornamentation in slithering geckos Lialis
      (Pygopodidae).
AB  - The skin of geckos is covered with countless microscopic protuberances (spines).
      This surface structure causes low wettability to water. During evolution,
      representatives of the recent gekkotan clade Pygopodidae started slithering on
      the ground. This manner of locomotion affected limb reduction resulting in a
      snake-like body. Regarding abrasion and frictional properties, a surface covered
      with gekkotan spines is a topography that hampers the snake-like locomotion mode.
      Using scanning electron microscopy, we investigated the shed skins of two
      pygopodid lizards, Lialis jicari (Papua snake lizard) and Lialis burtonis
      (Burton's legless lizard), in order to show epidermal adaptations to limbless
      locomotion. Our data showed that Pygopodidae differ from their relatives not only
      anatomically, but also in their epidermal microstructure. Scales of L. jicari
      have five different structural patterns on various body regions. Ventral scales
      have nanoridges, similar to those found on the ventralia of snakes. Surfaces of
      scales covering the jaw bones, have flattened spine-like microstructures that
      might be an adaptation to reduce abrasion. Dorsal scales have oblong microscopic
      bulges covered with nanoridges. Spines cover the undersides and the interstices
      of scales over the entire body of both species and in L. jicari also the top of
      dorsal head scales. Our measurements of surface wettability (surface free energy)
      show superhydrophobic properties of the spiny surfaces in comparison with the
      other microstructural patterns of other body parts. 

PMID- 24107535
TI  - Diurnal fluctuations in seawater pH influence the response of a calcifying
      macroalga to ocean acidification.
AB  - Coastal ecosystems that are characterized by kelp forests encounter daily pH
      fluctuations, driven by photosynthesis and respiration, which are larger than pH
      changes owing to ocean acidification (OA) projected for surface ocean waters by
      2100. We investigated whether mimicry of biologically mediated diurnal shifts in
      pH-based for the first time on pH time-series measurements within a kelp forest
      would offset or amplify the negative effects of OA on calcifiers. In a 40-day
      laboratory experiment, the calcifying coralline macroalga, Arthrocardia
      corymbosa, was exposed to two mean pH treatments (8.05 or 7.65). For each mean,
      two experimental pH manipulations were applied. In one treatment, pH was held
      constant. In the second treatment, pH was manipulated around the mean (as a step
      function), 0.4 pH units higher during daylight and 0.4 units lower during
      darkness to approximate diurnal fluctuations in a kelp forest. In all cases,
      growth rates were lower at a reduced mean pH, and fluctuations in pH acted
      additively to further reduce growth. Photosynthesis, recruitment and elemental
      composition did not change with pH, but delta(13)C increased at lower mean pH.
      Including environmental heterogeneity in experimental design will assist with a
      more accurate assessment of the responses of calcifiers to OA. 

PMID- 24107536
TI  - Reproductive isolation between phylogeographic lineages scales with divergence.
AB  - Phylogeographic studies frequently reveal multiple morphologically cryptic
      lineages within species. What is not yet clear is whether such lineages represent
      nascent species or evolutionary ephemera. To address this question, we compare
      five contact zones, each of which occurs between ecomorphologically cryptic
      lineages of skinks from the rainforests of the Australian Wet Tropics. Although
      the contacts probably formed concurrently in response to Holocene expansion from
      glacial refugia, we estimate that the divergence times (tau) of the lineage pairs
      range from 3.1 to 11.5 Ma. Multi-locus analyses of the contact zones yielded
      estimates of reproductive isolation that are tightly correlated with divergence
      time and, for lineages with older divergence times (tau > 5 Myr), substantial.
      These results show that phylogeographic splits of increasing depth represent
      stages along the speciation continuum, even in the absence of overt change in
      ecologically relevant morphology. 

PMID- 24107539
TI  - 17beta-estradiol protects mitochondrial functions through extracellular-signal
      regulated kinase in C2C12 muscle cells.
AB  - BACKGROUND/AIMS: We have previously shown that exposure to 17beta-estradiol (E2)
      prior to induction of apoptosis with H2O2 protects skeletal muscle cells against
      oxidative damage. However, the mechanism involved in the protective action of the
      hormone is poorly understood. In the present study, we focused on the mechanism
      by which ERK mediates this survival effect in connection with COXIV activity and
      mitochondrial membrane potential. METHODS: Immunocytochemistry, Western blot,
      cytochrome c oxidase complex IV (COXIV) activity, coimmunoprecipitation and JC-1
      dye by flow cytometry were carried out using C2C12 myoblasts as experimental
      model. RESULTS: E2 is able to activate ERK and then induces its translocation to
      mitochondria. Using the pharmacological inhibitor of ERK activation U0126 we show
      that E2, through ERK activation, is able to enhance COXIV activity. Moreover, the
      hormone increases the interaction between COXIV and ERK. Also, we found that
      hydrogen peroxide decreases COXIV activity and that preincubation of the cells
      with E2 prior to induction of apoptosis prevents this effect. In addition, we
      observe that the estrogen inhibits the collapse of mitochondrial membrane
      potential induced by H2O2, involving ERK and COXIV. CONCLUSION: Our data
      demonstrate that E2 promotes ERK activation and translocation to mitochondria
      preventing the decline in COXIV activity and in turn, alteration of mitochondrial
      membrane potential by oxidative stress, in C2C12 myoblasts.

PMID- 24107540
TI  - Speaking fundamental frequency and phonation time during work and leisure time in
      vocally healthy preschool teachers measured with a voice accumulator.
AB  - OBJECTIVE: More knowledge is needed about preschool teachers' voice use to
      identify voice behaviours related to work demands that increase the risk for
      vocal dysfunction. The purpose of this study was to: (1) determine if speaking
      fundamental frequency (F0) and phonation time differ between work and leisure
      time and (2) describe variation in F0 and phonation time across the workday in
      preschool teachers with healthy voices. METHODS: A portable voice accumulator was
      used to collect data on F0 and phonation time. Twelve vocally healthy female
      preschool teachers participated in recordings during both work and leisure time
      for 2 successive days. Their mean age was 35 years (range 21-53 years). RESULTS:
      Mean F0 was high during the working day (266 Hz) and decreased significantly
      after work (p < 0.0001). F0 was high also during leisure time (246 Hz) as
      compared to reference F0 values for Swedish females based on laboratory
      recordings. Phonation time at work varied widely among the participants, with an
      average of 12.0%, and decreased significantly to 5.5% during leisure time (p <
      0.0001). Most participants had few opportunities for voice rest during work.
      CONCLUSION: Swedish preschool teachers use high levels of F0 and phonation time
      during work compared to leisure time indicating high vocal load caused by work.
      To clarify the role of daily voice use in the causation of vocal dysfunction in
      this profession, recordings over several days are needed. In addition to F0 and
      phonation time, recordings of voice sound pressure level and background noise
      level seem important.

PMID- 24107542
TI  - Relationship between visual acuity and spectral domain optical coherence
      tomography retinal parameters in neovascular age-related macular degeneration.
AB  - PURPOSE: Relationship between spectral domain optical coherence tomography (SD
      OCT) and visual acuity (VA) in neovascular age-related macular degeneration
      (NVAMD). PROCEDURES: VA and SD-OCTs of 64 treatment-naive eyes with NVAMD were
      retrospectively collected at baseline and 1 year (n = 30). Retinal and subretinal
      spaces were manually analyzed. Volume and thickness measurements were correlated
      with VA. RESULTS: At baseline, lower VA correlated with increased volume of
      subretinal hyperreflective material (R = 0.4, p < 0.001) and with decreased
      volume of the photoreceptor layer (PRL, R = -0.4, p < 0.01). At 1 year, lower VA
      correlated with decreased volume of the retina (R = -0.7, p < 0.001), outer
      nuclear layer (R = -0.6, p < 0.05) and PRL (R = -0.7, p < 0.001). Decrease in VA
      after 1 year correlated with a decrease in PRL (R = 0.4, p < 0.05). CONCLUSIONS:
      Quantitative analysis of SD-OCT revealed correlations between VA and retinal and
      subretinal morphological changes in NVAMD. MESSAGE: Atrophy of the outer retina
      is an important correlate for lower VA in NVAMD.

PMID- 24107543
TI  - Genetic influence of COMT and BDNF gene polymorphisms on resilience in healthy
      college students.
AB  - PURPOSE: Resilience refers to the individual positive capacity to cope with
      stress and to restore homeostasis, which may be mediated by adaptive
      neurobiological changes in the brain. We investigated the genetic influence of
      the catechol-O-methyltransferase (COMT) Val158Met and the brain-derived
      neurotrophic factor (BDNF) Val66Met for individual differences in resilience in
      healthy Korean college students. METHODS: A sample of 321 healthy college
      volunteers (167 males, 154 females) was assessed by genotyping and with the 25
      item Connor-Davidson Resilience Scale. Two-way analysis of covariance was used to
      test the association between participants' COMT and BDNF functional polymorphisms
      and their resilience. RESULTS: A significant main effect of the COMT polymorphism
      on resilience and a gene-gene interaction effect between the COMT and BDNF on
      resilience were observed for males. Male subjects with the COMT Met-present
      genotype had a significantly higher resilience than those with the Val/Val
      genotype. Among males with the COMT Val/Val genotype, subjects with the
      homozygous Val allele of the BDNF tended to have lower resilience than the BDNF
      Met carriers, while among males with the COMT Met-present genotype, those with
      the homozygous Val allele of the BDNF tended to have higher resilience than BDNF
      Met carriers. No main or interaction effects of the COMT and BDNF on resilience
      were observed for females. CONCLUSION: These findings suggest the effects of COMT
      Val158Met polymorphism on resilience could be modulated by BDNF Val66Met
      polymorphism in males.

PMID- 24107544
TI  - Lymphoscintigraphic evaluation of manual lymphatic therapy: the Godoy & Godoy
      technique.
AB  - The objective of this study was to evaluate the transport of radiotracers in
      lymphatic collectors during manual lymphatic therapy. The legs of four male and
      two female patients with leg lymphedema were assessed using lymphoscintigraphy
      before, during and after manual lymphatic therapy. The ages of the patients,
      treated in Hospital de Base in Sao Jose do Rio Preto, ranged from 42 to 64 years
      with a mean age of 51.2 years. Consecutive patients with grade II leg lymphedema
      were enrolled in this study. Patients with lymphedema secondary to
      lymphadenectomy, active infections and weight greater than 130  kg were excluded.
      Patients were submitted to manual lymphatic therapy, which consists of the
      collapsing of capillaries using manual compression which is then slid along the
      skin in a stroking action in the direction of the lymph flow within lymphatic
      vessels towards the lymph nodes. Two dynamic studies were performed; the first
      was over 40 minutes (3 images every 10 minutes) which was immediately followed by
      an entire body scan. A second dynamic evaluation was performed taking images at
      10-second intervals over 2 minutes during manual lymphatic therapy. To evaluate
      the displacement of radiotracers, the path of lymphatic collectors from the knee
      to a lymph node in the upper thigh was divided into five similarly sized regions
      of interest. The concentration of radiotracer was quantified in each of the
      regions of interest. The paired t-test was used for statistical analysis with an
      alpha error of 5% (p value < 0.05) being considered statistically relevant. The
      results show statistically significant differences in the number of particles in
      all the regions of interest comparing before and after treatment (two-tail paired
      t-test: p value < 0.0001). Manual lymphatic therapy improves the transport of
      radiotracers in lymphatic collectors.

PMID- 24107545
TI  - PIRPLE: a penalized-likelihood framework for incorporation of prior images in CT
      reconstruction.
AB  - Over the course of diagnosis and treatment, it is common for a number of imaging
      studies to be acquired. Such imaging sequences can provide substantial patient
      specific prior knowledge about the anatomy that can be incorporated into a prior
      image-based tomographic reconstruction for improved image quality and better dose
      utilization. We present a general methodology using a model-based reconstruction
      approach including formulations of the measurement noise that also integrates
      prior images. This penalized-likelihood technique adopts a sparsity enforcing
      penalty that incorporates prior information yet allows for change between the
      current reconstruction and the prior image. Moreover, since prior images are
      generally not registered with the current image volume, we present a modified
      model-based approach that seeks a joint registration of the prior image in
      addition to the reconstruction of projection data. We demonstrate that the
      combined prior-image- and model-based technique outperforms methods that ignore
      the prior data or lack a noise model. Moreover, we demonstrate the importance of
      registration for prior-image-based reconstruction methods and show that the prior
      image-registered penalized-likelihood estimation (PIRPLE) approach can maintain a
      high level of image quality in the presence of noisy and undersampled projection
      data. 

PMID- 24107547
TI  - Cytohistologic correlation in premenopausal and postmenopausal women.
AB  - OBJECTIVE: This study was conducted to compare the correlation between Pap smear
      and colposcopic biopsy findings in premenopausal and postmenopausal women. STUDY
      DESIGN: A total of 68,738 ThinPrep Pap smears were done in 2011 in our
      institution, and of these, 865 of the women (787 premenopausal and 78
      postmenopausal) had subsequent colposcopic directed biopsies performed within 3
      months of obtaining the results. RESULTS: We discovered that 52.5% of the Pap
      smears in postmenopausal women versus 33.6% in premenopausal women were
      classified as false positive (FP), with respect to the biopsy, and of these, 47.6
      vs. 17% cases had no transformation zone (TZ) on the subsequent biopsies,
      respectively. Interestingly, with respect to high-risk human papilloma virus
      (hrHPV) testing in patients having both Pap smear and biopsies performed, we
      found the Pap smear diagnoses were a better predictor of positive hrHPV than the
      respective colposcopic biopsies. CONCLUSION: As many of the FP postmenopausal
      women had an absent TZ (47.6%) on biopsy, and because the majority (83.3%) of
      those which had hrHPV testing were positive, we suggest that this indicates a
      potential sampling error on biopsy, perhaps due to an inability to visualize the
      involved area in older women due to an upward migration of the TZ.

PMID- 24107546
TI  - A population-based dietary inflammatory index predicts levels of C-reactive
      protein in the Seasonal Variation of Blood Cholesterol Study (SEASONS).
AB  - OBJECTIVE: To perform construct validation of the population-based Dietary
      Inflammatory Index (DII) using dietary data from two different dietary
      assessments and serum high-sensitivity C-reactive protein (hs-CRP) as the
      construct validator. DESIGN: Using data derived from (i) three 24 h dietary
      recalls (24HR) at baseline and at the end of each subsequent quarter (i.e. up to
      fifteen over a year) and (ii) a 7 d dietary recall (7DDR) measured at baseline
      and then quarterly, regression analyses were conducted to test the effect of the
      DII score on serum hs-CRP as dichotomous (<=3 mg/l, >3 mg/l), while controlling
      for important potential confounders. SETTING: Existing data from the Seasonal
      Variation of Blood Cholesterol Study (SEASONS), a longitudinal observational
      study of healthy participants recruited in Worcester, MA, USA and participants
      were followed for 1 year. SUBJECTS: Participants who had at least one hs-CRP
      measurement over her/his 1-year participation (n 495 for 24HR, n 559 for 7DDR).
      RESULTS: Higher DII scores were associated with values of hs-CRP >3 mg/l (OR =
      1.08; 95 % CI 1.01, 1.16, P = 0.035 for the 24HR; and OR = 1.10; 95 % CI 1.02,
      1.19, P = 0.015 for the 7DDR). CONCLUSIONS: The population-based DII was
      associated with interval changes in hs-CRP using both the 24HR and 7DDR. The
      success of this first-of-a-kind attempt at relating individuals' intakes of
      inflammation-modulating foods using this refined DII, and the finding that there
      is virtually no drop-off in predictive capability using a structured
      questionnaire in comparison to the 24HR standard, sets the stage for use of the
      DII in a wide variety of other epidemiological and clinical studies.

PMID- 24107548
TI  - Analysis of MAT3 gene expression in NSCLC.
AB  - BACKGROUND: Many studies have suggested different roles of Metastasis-associated
      protein 3 (MAT3) in different types of human cancers. However, expression of MAT3
      in primary lung cancer and its relationship with clinicopathological factors have
      not been examined and the biological roles of MTA3 in lung cancer cells are still
      unclear. METHODS: The expression of MAT3 mRNA and protein were detected with
      quantitative real-time RT-PCR and immunohistochemical methods in 118 NSCLC
      samples and corresponding non-neoplastic samples. Survival curves were made with
      follow-up data. The relations of the prognosis with clinical and pathological
      characteristics were analyzed. RESULTS: The expression level of MAT3 mRNA and the
      positive rate of MAT3 protein were significantly higher in NSCLC samples than
      that in non-neoplastic samples, and in NSCLC samples with lymph node metastasis
      than that in NSCLC samples without lymph node metastasis (P < 0.01). MAT3 mRNA
      expression level was a risk factor of lymph node metastasis in patients with
      NSCLC (P = 0.006). There were significant differences in survival curves between
      lymph node metastatic group and non-metastatic group (P = 0.000), among groups of
      MAT3 positive and negative (P = 0.000), among groups of TNM stage I, II and III
      (P = 0.000) and among groups of tumor status T1, T2 and T3T4 (P = 0.000); but no
      statistical significance between male patients and female patients (P = 0.516),
      between >= 60 years old patients and <60 years old patients (P = 0.133), between
      histology types adenocarcinoma and squamous cell carcinoma (P = 0.865) and
      between well differentiation and moderate-poor differentiation (P = 0.134). The
      level of MAT3 mRNA (P = 0.000) and protein (P = 0.000) were risk factors of
      survival. CONCLUSION: Our study showed that MAT3 over-expression in NSCLC tissue,
      and MAT3 mRNA level is a risk factor of lymph node metastasis. The level of MAT3
      mRNA and protein were risk factors of survival in patients with NSCLC. It
      suggested that this antigen could be used as a simple and efficient parameter
      with which to identify high-risk patients. VIRTUAL SLIDES: The virtual slides for
      this article can be found here:
      http://www.diagnosticpathology.diagnomx.eu/vs/5585901065503943.

PMID- 24107550
TI  - Policy decisions on endocrine disruptors should be based on science across
      disciplines: a response to Dietrich et al.

PMID- 24107549
TI  - Distinct disease phenotypes linked to different combinations of GAA mutations in
      a large late-onset GSDII sibship.
AB  - BACKGROUND: Glycogenosis type II (GSDII or Pompe disease) is an autosomal
      recessive disease, often characterized by a progressive accumulation of glycogen
      within lysosomes caused by a deficiency of alpha-1,4-glucosidase (GAA; acid
      maltase), a key enzyme of the glycogen degradation pathway. To date, more than
      326 different mutations in the GAA gene have been identified in patients with
      GSDII but the course of the disease is difficult to be predicted on the basis of
      molecular genetic changes. Studies on large informative families are advisable to
      better define how genetics and non genetics factors like exercise and diet may
      influence the clinical phenotype. METHODS AND RESULTS: In this study, we report
      on clinical, instrumental, and pathological features as well as on molecular
      analysis of a family with 10 out of 13 siblings affected by late-onset Pompe
      disease. Three mutations segregated in the family, two of which are novel
      mutations. Siblings showing a more severe phenotype were compound heterozygous
      for c.118C > T [p.R40X] and c.2647-7G > A [p.N882fs] on GAA, whereas, two
      patients showing a mild phenotype were compound heterozygous c.2647-7G > A
      [p.N882fs] and c.2276G > C [p.G759A] mutations. Quantitative expression analysis
      showed, in the patients carrying p.R40X/ p.N882fs, a significant (p 0.01)
      correlation between the levels of expression of the mutated allele and the age at
      onset of the disease. CONCLUSIONS: As far as we know, this is the largest
      informative family with late-onset Pompe disease described in the literature
      showing a peculiar complex set of mutations of GAA gene that may partially
      elucidate the clinical heterogeneity of this family.

PMID- 24107551
TI  - Anti-oxLDL antibodies are clinically insignificant for stroke patients.
AB  - OBJECTIVES: The question about anti-oxidized low-density lipoprotein antibodies
      (anti-oxLDL Abs) involvement in the pathogenesis of atherosclerosis-related
      ischemic stroke is still open. The aim of this study was to determine how anti
      oxLDL Abs are involved in the pathogenesis of atherosclerosis-related ischemic
      stroke and identify the main risk factors for stroke, such as arterial
      hypertension, diabetes mellitus type 2, dyslipidemia, and atherosclerotic changes
      in the common and internal carotid arteries. MATERIAL AND METHODS: A total of 40
      stroke patients and 25 age- and sex-matched healthy individuals were included in
      the study. For each subject, IgG anti-oxLDL Abs expression in peripheral blood
      was assessed and analyzed in relation to clinical data, carotid Doppler
      ultrasonography results, and results of peripheral blood laboratory tests,
      including inflammatory parameters and lipid profile. RESULTS: The blood level of
      assessed antibodies was significantly higher in stroke patients than in control
      group. It did not relate to stroke severity and stroke outcome. The relationship
      between anti-oxLDL Abs and carotid plaques hyperechogenicity was observed. The
      antibodies concentration was significantly higher in patients with diabetes
      mellitus type 2 and also positively correlated with C-reactive protein blood
      level. However, multiple regression method did not confirm their independent
      influence. DISCUSSION: Patients with atherogenic ischemic stroke may have
      significantly higher anti-oxLDL Abs concentrations. This should be interpreted as
      an attempt to limit the consequences of oxLDL production; however, this
      phenomenon does not seem to protect patients against cerebrovascular events.

PMID- 24107552
TI  - Optimal finite-range atomic basis sets for liquid water and ice.
AB  - Finite-range numerical atomic orbitals are the basis functions of choice for
      several first principles methods, due to their flexibility and scalability.
      Generating and testing such basis sets, however, remains a significant challenge
      for the end user. We discuss these issues and present a new scheme for generating
      improved polarization orbitals of finite range. We then develop a series of high
      accuracy basis sets for the water molecule, and report on their performance in
      describing the monomer and dimer, two phases of ice, and liquid water at ambient
      and high density. The tests are performed by comparison with plane-wave
      calculations, and show the atomic orbital basis sets to exhibit an excellent
      level of transferability and consistency. The highest-order bases (quadruple
      zeta) are shown to give accuracies comparable to a plane-wave kinetic energy
      cutoff of at least ~1000 eV for quantities such as energy differences and ionic
      forces, as well as achieving significantly greater accuracies for total energies
      and absolute pressures.

PMID- 24107553
TI  - Optimal blood glucose control in severely burned patients: a long way to go, but
      one step closer.
AB  - Over the past years there has been a significant decrease in mortality and
      morbidity in patients suffering from severe burns due to improved burn wound
      management and approaches in critical care. Survival is no longer the exception,
      but unfortunately death still occurs. One of the key elements concerning state-of
      the-art burn care is blood glucose control and insulin therapy; it is well known
      that burn-induced hyperglycaemia is associated with adverse clinical outcomes.
      However, controversy for insulin therapy and tight glycaemic control in
      critically ill and burn patients exists. The increased incidence of hypoglycaemia
      is the dominant argument against this treatment, because hypoglycaemia is also
      associated with an increased risk for death in critically ill patients. Taking
      all current data together, insulin therapy appears both a friend and a foe in the
      treatment of ICU patients. In order to overcome the limits of tight glycaemic
      control resulting from hypoglycaemic episodes, current efforts have been directed
      towards the development of protocols allowing for implementation of clinically
      feasible and safe guidelines. Among the strategies addressing this problem are
      closed loop techniques, which are supported by studies demonstrating their
      capability of exerting tight glycaemic control without the risk of developing
      hypoglycaemic episodes. Although closed loop techniques have become readily
      available, we require further evidence to ensure their safety in various ICU
      environments, notably in ICUs dealing with burn patients. Nonetheless, it is
      important to emphasise that glycaemic control and adequate insulin therapy are
      crucial factors for the final outcome (survival) and require our attention. 

PMID- 24107554
TI  - Gestational undernourishment modifies the composition of skeletal muscle
      transverse tubule membranes and the mechanical properties of muscles in newborn
      rats.
AB  - BACKGROUND/AIMS: [corrected] Skeletal muscle (SM) constitutes more than 40% of
      the body weight in adulthood. Transports dietary glucose mainly through the
      insulin-dependent glucose transporter (Glut-4) located in the Transverse tubule
      membrane system (TT). The TT development ends shortly after birth. The TT
      membrane hosts the proteins involved in excitation-contraction coupling and
      glucose uptake. Glycaemic regulation through movement is a key function of fully
      developed skeletal muscle. In this study, we aimed to characterize the effect of
      gestational undernourishment (GUN) in rats GLUT-4 expression and on the
      protein/lipid content of the TT membranes. We also examined the effect of GUN on
      the mechanical properties of muscles as an indication of the metabolic condition
      of the SM at birth. METHODS: Isolated TT membrane from SM of GUN rats were used
      to study lipid/protein content and protein stability by differential scanning
      calorimetry. The effect of GUN on the SM mechanical properties was determined in
      isolated Extensor Digitorum Longus (EDL) muscle. RESULTS: We demonstrate that
      compared to control, GUN in the new-born produces; i) decreases body weight; ii)
      diminution in SM mass; iii) decreases the formation of TT membranes; iv)
      expresses TT membrane proteins with higher thermal stability. The TT membrane
      expression of GLUT-4 in GUN offspring was twice that of controls. The isolated
      EDL of GUN offspring was 20% stronger as measured by contractile force and more
      resistant to fatigue relative to controls. CONCLUSION: These results provide the
      first evidence of adaptive changes of the SM in new-borns exposed to severe
      gestational food restriction. The effects of GUN on muscle at birth are the first
      step toward detrimental SM metabolic function, contributing to the
      physiopathology of metabolic diseases in adulthood.

PMID- 24107556
TI  - Response letter to H Honda et al,--Raltegravir use in warfarin treated HIV
      patients (Int J STD AIDS 2012;23:903-904).

PMID- 24107555
TI  - At-risk but viable myocardium in a large animal model of non ST-segment elevation
      acute coronary syndrome: cardiovascular magnetic resonance with ex vivo
      validation.
AB  - BACKGROUND: Patients with non-ST-segment elevation acute coronary syndrome (NSTE
      ACS) have varying degrees of salvageable myocardium at risk of irreversible
      injury. We hypothesized that a novel model of NSTE-ACS produces acute myocardial
      injury, measured by increased T2 cardiovascular magnetic resonance (CMR), without
      significant necrosis by late gadolinium enhancement (LGE). METHODS: In a canine
      model, partial coronary stenosis was created and electrodes placed on the
      epicardium. Myocardial T2, an indicator of at-risk myocardium, was measured pre-
      and post-tachycardic pacing. RESULTS: Serum troponin-I (TnI) was not detectable
      in unoperated sham animals but averaged 1.97 +/- 0.72 ng/mL in model animals.
      Coronary stenosis and pacing produced significantly higher T2 in the affected vs.
      the remote myocardium (53.2 +/- 4.9 vs. 43.6 +/- 2.8 ms, p < 0.01) with no
      evident injury by LGE. Microscopy revealed no significant irreversible cellular
      injury. Relative respiration rate (RRR) of affected vs. remote myocardial tissue
      was significantly lower in model vs. sham animals (0.72 +/- 0.07 vs. 1.04 +/-
      0.07, p < 0.001). Lower RRR corresponded to higher final TnI levels (R(2) = 0.83,
      p = 0.004) and changes in CaMKIID and mitochondrial gene expression. CONCLUSIONS:
      A large animal NSTE-ACS model with mild TnI elevation and without ST elevation,
      similar to the human syndrome, demonstrates signs of acute myocardial injury by
      T2-CMR without significant irreversible damage. Reduced tissue respiration and
      associated adaptations of critical metabolic pathways correspond to increased
      myocardial injury by serum biomarkers in this model. T2-CMR as a biomarker of at
      risk but salvageable myocardium warrants further consideration in preclinical and
      clinical studies of NSTE-ACS.

PMID- 24107557
TI  - Simple preparation of microstructure by using an organic-inorganic raspberry-like
      hybrid as a building block.
AB  - A single-step strategy has been developed for synthesizing a micrometer-sized
      structure by using the raspberry-like hybrid as a building block comprising a
      repeated sequence of a three-dimensional gold nanoparticle (AuNP)-aniline
      oligomer-AuNP arrangement. The hybrid holds a high density of highly dispersible
      AuNPs without any contact with each other, and therefore the microstructure has
      many nanometer-sized gaps between the adjacent AuNPs for both electrical and
      optical sensing. We have discussed how the formation mechanism of the
      microstructure is based on using the hybrid. 

PMID- 24107558
TI  - Aging effect of 137Cs obtained from 137Cs in the Kanto loam layer from the
      Fukushima nuclear power plant accident and in the Nishiyama loam layer from the
      Nagasaki A-bomb explosion.
AB  - We measured (134)Cs and (137)Cs in the surface soil of the Kanto loam in the
      eastern Tokyo metropolitan area and the Nishiyama loam in Nagasaki, Japan. The
      observed (137)Cs deposition in the Kanto loam from the Fukushima nuclear power
      plant (NPP) accident ranged from 4.0 to 77 kBq m(-2), which corresponds to 0.3-5
      times of that in the Nishiyama loam. The (137)Cs retardation factor in the Kanto
      loam obtained seven months after the Fukusima NPP accident and in the Nishiyama
      loam after 36 and 38 years from the detonation of the Pu atomic bomb (A-bomb)
      ranged from 180 to 260 and 2000 to 10,000, respectively. This difference in the
      retardation factors is attributed to an aging effect that corresponds to seven
      months and 36 to 38 years after the deposition of (137)Cs occurred on the soil
      minerals.

PMID- 24107559
TI  - Determination of ultra-trace mercury(II) by flow-injection/anodic stripping
      voltammetry using a track-etched microporous membrane electrode.
AB  - A new flow-injection/anodic stripping voltammetry has been demonstrated to assess
      ultra-trace mercury(II) using track-etched microporous membrane electrodes. The
      electrodes were prepared by the sputtering of gold or platinum onto both sides of
      a membrane filter with a smooth flat surface and with cylindrical pores having
      uniform diameter. The deposition of mercury from a mercury(II) solution was
      performed while the sample solution flowed through the membrane electrodes. After
      the deposition step, an anodic stripping voltammogram was obtained by sweeping
      the potential from 0 to +0.8 V vs. Ag/AgCl. In this case, the sample solution
      flowed through the pores of the 10-MUm-thick membrane filters. Efficient
      electrolysis occurred during passage of the sample solution through the
      electrode, of which the pore size was 0.4 MUm. In this study, the voltammetry
      described above was demonstrated using an FIA system. The continuous-flow mode
      showed a detection limit of 0.04 MUg L(-1) when the experimental conditions of
      the flow rate and the deposition time were set at 0.5 mL min(-1) and 180 s. In
      the sample-injection mode equipped with a 1-mL sample loop, a linear relation was
      found for 0.5-4.0 MUg L(-1) of a mercury(II) standard solution (r = 0.995). The
      detection limit was 0.05 MUg L(-1). This method was applied to the ultra-trace
      determination of mercury(II) in river-water samples.

PMID- 24107560
TI  - Preconcentration of total mercury from river water by anion exchange mechanism.
AB  - A simple and cheap analytical technique was developed for the measurement of
      total mercury in river water samples using inductively coupled plasma-mass
      spectrometry (ICP-MS). It is based on the direct complexation of mercury ions
      using iodide and a cationic surfactant in water for its subsequent solid-phase
      extraction. Mercury ions are retained on the silica phase as ion pairs in the
      presence of iodide ions and dodecyltrimethylammonium bromide. Parameters having
      influential influence on the retention of Hg(II) were investigated: sample
      flowrate, eluent type, sample volume, iodide and surfactant concentrations. The
      retained mercury ions are stripped off from silica phase using 10 mL of 8 mol L(
      1) HNO3 and quantified by ICP-MS. An enrichment factor of 50 was achieved with a
      maximum adsorption capacity of 718 MUg Hg(II) g(-1). The limit of detection of
      Hg(II) was 8 pg mL(-1). The developed method was applied for the determination of
      total mercury in river and tap-water samples. 

PMID- 24107561
TI  - New antibody and immunoassay pretreatment strategy to screen polychlorinated
      biphenyls in Korean transformer oil.
AB  - Development and modifications are described that expand the application of an
      immunoassay from the detection of Kanechlors (Japanese technical PCBs mixtures)
      to the detection of Aroclors (U. S. technical PCB mixtures, used in Korea) in
      contaminated Korean transformer oil. The first necessary modification was the
      development of a new antibody with a reactivity profile favorable for Aroclors.
      The second modification was the addition of a second column to the solid-phase
      extraction method to reduce assay interference caused by the Korean oil matrix.
      The matrix interference is suspected to be caused by the presence of synthetic
      oils (or similar materials) present as contaminants. The modified assay was
      validated by comparison to high-resolution gas chromatography/high-resolution
      mass spectrometry analysis, and was shown to be tolerant of up to 10% of several
      common synthetic insulating oils. Finally the screening performance of the
      modified assay was evaluated using 500 used transformer oil samples of Korean
      origin, and was shown to have good performance in terms of false positive and
      false negative rates. This report provides evidence for the first establishment
      of immunoassay screening for Aroclor based PCB contamination in Korean
      transformer oil. 

PMID- 24107562
TI  - Luminescence amplification by enzymatic Eu2+ oxidation to Eu3+ for time-resolved
      peroxidase activity measurement.
AB  - A novel peroxidase activity assay was developed for horseradish peroxidase (HRP)
      and myeloperoxidase (MPO), in which substrate Eu(2+) was catalytically oxidized
      to Eu(3+), and the Eu(3+) luminescence was enhanced by the addition of sensitizer
      4,4'-bis(1",1",1",2",2",3",3"-hepatafluoro-4",6"-hexanedione-6"-yl)chlorosulfo-o
      terphenyl (BHHCT) for time-resolved measurement of the BHHCT-Eu(3+) complex.
      Since BHHCT-Eu(3+) has a long lifetime (more than 500 MUs), typical of Eu(3+)
      oxidation state, and the emission wavelength (615 nm) is totally different from
      those of Eu(2+) complexes, time-resolved luminescence measurement of the Eu(3+)
      complex enabled suppressed background and high signal/background ratio. The
      present method was successfully applied to monitor the oxidative stress level,
      which is closely associated with peroxidase activity level, in rat heart muscle
      homogenates. Notable parallel temporal change was observed for peroxidase
      activity and 4-hydroxynonenal (HNE) concentration after lipopolysaccharide (LPS)
      injection for induction of oxidative stress in rats. Such a relation does not
      contradict the oxidative stress mechanism that HNE is produced via lipid
      peroxidation, which is caused by the (*)OH radical generated by peroxidase
      activity. 

PMID- 24107563
TI  - Analysis of the surface coverage of a self-assembled monolayer of octadecyl
      silane on a Si(100) surface by infrared external-reflection spectroscopy.
AB  - The coverage of a self-assembled monolayer (SAM) of octadecyl silane on a silicon
      surface is analyzed by infrared external-reflection spectrometry via molecular
      orientation analysis. A commercially available octadecyl trimethoxy silane (ODS)
      solution is employed, which readily reacts with an oxidized surface of Si(100)
      prepared by a UV/ozone treatment in an ambient condition to yield a highly
      reproducible SAM. With the present technique, a very flat surface with no holes
      is obtained in the entire area of the SAM. IR external-reflection spectra of the
      SAM apparently indicate that the alkyl chains are highly ordered having the all
      trans zigzag conformation, and the molecular orientation agrees with that of a
      Langmuir-Blodgett (LB) monolayer film of octadecanoic acid. Since the orientation
      analysis is based on an assumption that the surface is fully covered by the SAM
      as the LB film, the agreement of the orientation confirms that the surface
      coverage of the present SAM on Si(100) is on the same level as the LB film. 

PMID- 24107564
TI  - Analysis of drugs illegally added into Chinese traditional patent medicine using
      surface-enhanced Raman scattering.
AB  - Illegal chemicals, which could cause unpredictable side effects, may be added
      into traditional Chinese medicine (TCM) for a rapid healing effect. In this
      report, a surface-enhanced Raman scattering (SERS) analysis method for five kinds
      of illegally added drugs (rosiglitazone maleate, phenformin hydrochloride,
      metformin hydrochloride, pioglitazone hydrochloride and sibutramine
      hydrochloride) in Chinese traditional patent medicine (CTPM) has been
      demonstrated, including simultaneous detections of drug mixtures with CTPM.
      Silver colloidal, prepared by a sodium citrate reaction, was used as a SERS
      substrate. The optimum pH condition for each drug has also been explored because
      of its combined effect on protonation, surface charge, repulsion of an analyte
      and nanoparticles. Furthermore, the simultaneous detection of two or three kinds
      of these chemicals has been carried out. Characteristic peaks are employed for
      qualitative analysis. This is the first research using SERS for the analysis of
      drug mixtures in CTPM without any separation process. 

PMID- 24107565
TI  - A cytosine-rich DNA decorated gold nanoparticles surface enhanced Raman
      scattering platform for sensitive and selective detection of silver ions.
AB  - In this work, we developed a label-free, homogeneous surface-enhanced Raman
      scattering (SERS) platform for the rapid, simple and sensitive detection of Ag(+)
      by using the unmodified gold nanoparticles (AuNPs). It utilizes the different
      absorption properties of single-strand DNA (ssDNA) and double-strand DNA (dsDNA)
      on citrate-coated AuNPs and specific interactions between Ag(+) and cytosine
      cytosine pairs. In the presence of Ag(+), the structure of ssDNA containing rich
      cytosine will form a duplex, resulting in the salt-induced aggregation of gold
      nanoparticles; the corresponding SERS signal transduction can be observed due to
      the plasmonic coupling of metallic nanoparticles. The assay possesses a superior
      signal-to-background ratio as high as ~35.8 with a detection limit of 15 nM. This
      approach is not only rapid and convenient in operation, but also shows excellent
      selectivity, which makes it possible to detect Ag(+) in actual samples. 

PMID- 24107566
TI  - Tentative identification of torulene cis/trans geometrical isomers isolated from
      Sporidiobolus pararoseus by high-performance liquid chromatography-diode array
      detection-mass spectrometry and preparation by column chromatography.
AB  - The major carotenoids (beta-carotene, gamma-carotene, torulene, and torularhodin)
      were determined by high-performance liquid chromatography, with torulene present
      in the largest amount (167.0 MUg/g), followed by torularhodin (113.4 MUg/g), beta
      carotene (52.1 MUg/g) and gamma-carotene (15.4 MUg/g). In addition, cis/trans
      torulene isomers were further identified by developing an HPLC-DAD coupled with
      an atmospheric-pressure chemical ionization (APCI) MS method, following isolation
      and purification torulene from crude pigments by column chromatography. A total
      of 8 torulene geometrical isomers were resolved within 60 min by employing a YMC
      C30 column and a binary gradient mobile phase consisting of methanol-methyl tert
      butyl ether-water, (50:47.5:2.5, v/v/v) (A) and methanol-methyl tert-butyl ether
      water, (8:90:2, v/v/v) (B). Geometrical carotenoid isomers behave differently
      with respect to bioavailability; therefore, it is of great importance to expand
      our knowledge on their biological roles to determine the appropriate method to
      separate torulene cis/trans isomers. 

PMID- 24107567
TI  - Specific distribution behavior of a ternary mixture of solvents fed into bent and
      wound microchannels in microchips.
AB  - The tube radial distribution of ternary solvents (water-hydrophilic/hydrophobic
      organic mixture) fed into bent and wound microchannels in a microchip was
      examined by fluorescence observations of dyes dissolved in the solvents under
      laminar flow conditions. Four kinds of microchips incorporating bent
      microchannels were used, together with a microchip with a straight channel. The
      microchannels had different bending times (2, 4, or 12 times), bending radii
      (0.8, 2.3, or 3 mm), and total channel lengths (80, 120, 200, or 500 mm). A water
      acetonitrile (hydrophilic)-ethyl acetate (hydrophobic) mixture containing
      relatively hydrophilic Eosin Y (green) and hydrophobic perylene (blue) was
      delivered into the bent microchannels in the microchips. The fluorescence of the
      green and blue dyes enabled us to observe the specific radial distribution
      behavior of the ternary solvents in the bent micro channels at 0 degrees C,
      including liquid-liquid interfaces. Further, the radial distribution pattern of
      the solvents was clearly observed in the wound microchannel (bending radius, ca.
      0.1 mm; real total channel length, 500 mm; and apparent straight channel length,
      40 mm) at 20 degrees C (room temperature) as well as 0 degrees C. It was found
      that the radial distribution behaviors of the solvents were successfully
      generated in even specific microchannels including various types of curves under
      the present conditions. 

PMID- 24107568
TI  - Simple preparation of solid-phase microextraction fiber with cation exchange
      capacities using poly(butadiene-maleic acid).
AB  - A simply way was proposed to prepare solid-phase microextraction (SPME) fiber
      with cation-exchange functional groups by the thermally initiated radical
      polymerization of poly(butadiene-maleic acid) (PBMA) copolymer onto a silica
      capillary. The capacity of the fiber coating could be easily controlled by
      fabricating successive layers of PBMA. The performance of the fiber combined with
      ion chromatography was evaluated by choosing Mg(2+) and Ca(2+) as model analytes;
      ~13 and ~51-fold enrichment factors for Mg(2+) and Ca(2+) were obtained,
      respectively. 

PMID- 24107570
TI  - Evaluation of the induced electric field and compliance procedure for a wireless
      power transfer system in an electrical vehicle.
AB  - In this study, an induced electric field in a human body is evaluated for the
      magnetic field leaked from a wireless power transfer system for charging an
      electrical vehicle. The magnetic field from the wireless power transfer system is
      modelled computationally, and its effectiveness is confirmed by comparison with
      the field measured in a previous study. The induced electric field in a human
      standing around the vehicle is smaller than the allowable limit prescribed in
      international guidelines, although the magnetic field strength in the human body
      is locally higher than the allowable external field strength. Correlation between
      the external magnetic field and the induced electric field is confirmed to be
      reasonable at least in the standing posture, which is the case discussed in the
      international standard. Based on this finding, we discussed and confirmed the
      applicability of a three-point magnetic field measurement at heights of 0.5, 1.0,
      and 1.5 m for safety compliance. 

PMID- 24107571
TI  - Eisenmenger's syndrome: in search of the best vasodilator.

PMID- 24107572
TI  - Will formal genetics become dispensable?

PMID- 24107574
TI  - Chromosomes of Iberian Leuciscinae (Cyprinidae) revisited: Evidence of genome
      restructuring in homoploid hybrids using dual-color FISH and CGH.
AB  - Iberian Leuciscinae have been used in many studies as models to explore topics
      such as hybridization, allopolyploidy, modes of reproduction, and evolution. This
      article focuses on the contribution of cytogenomics to foster research in this
      group of cyprinid fish. Conventional and molecular banding results were reviewed,
      facilitating comparative analysis between nase and chub taxa inhabiting
      Portuguese freshwaters. Hybridization is known to occur within both Chondrostoma
      s.l. and Squalius genera although polyploidy has only been reported in the
      latter; the reasons behind such differential genome flexibility remain
      unidentified. FISH tools allowed recognizing additional chromosome markers,
      confirming NOR polymorphism and distinguishing species and their hybrids.
      Recombination and genome instability were detected in homoploid and polyploid
      hybrid genomes supporting active NOR transposition. However, the multiplication
      of rDNAs in these species does not seem to be associated with Rex3 retroelement,
      though hybrids were not surveyed. CGH and GISH allowed reaffirming the hybrid
      origin of S. alburnoides and confirming that the conservative karyotype patterns
      within Iberian leuciscines are restricted to the macrostructure. Current data
      also support the usefulness of mapping repetitive DNAs, especially for nonmodel
      compact genomes with less variable karyotypes and sequence data resources
      unavailable, like in many cyprinid lineages.

PMID- 24107575
TI  - Patient radiation exposure and image quality evaluation with the use of iDose4
      iterative reconstruction algorithm in chest-abdomen-pelvis CT examinations.
AB  - The aim of this study is to evaluate the effect of iDose(4) iterative
      reconstruction algorithm on radiation dose and imaging quality at chest-abdomen
      pelvis (CAP) CT examinations. Seventeen patients were considered; all patients
      had a previous CT scan with the standard filter back-projection (FBP) protocol
      and a follow-up scan with the iDose(4) protocol at the same scanner. Image noise,
      signal-to-noise ratio (SNR) and contrast-to-noise ratio (CNR) were objectively
      calculated. Two radiologists evaluated noise, sharpness, contrast, diagnostic
      confidence and artefacts. Radiation exposure quantities were calculated. iDose(4)
      resulted in 46 % dose reduction combined with significantly lower noise and
      higher SNR and CNR compared with FBP. iDose(4) images had significantly lower
      subjective image noise and enhanced sharpness and contrast. Diagnostic confidence
      was high and image artefacts were minor for both algorithms. iDose(4) provides
      great potential for reducing patient radiation burden while improving imaging
      quality in CAP CT examinations. 

PMID- 24107577
TI  - Prevalence and patterns of cooking dinner at home in the USA: National Health and
      Nutrition Examination Survey (NHANES) 2007-2008.
AB  - OBJECTIVE: To measure the prevalence of cooking dinner at home in the USA and
      test whether home dinner preparation habits are associated with socio-economic
      status, race/ethnicity, country of birth and family structure. DESIGN: Cross
      sectional analysis. The primary outcome, self-reported frequency of cooking
      dinner at home, was divided into three categories: 0-1 dinners cooked per week
      ('never'), 2-5 ('sometimes') and 6-7 ('always'). We used bivariable and
      multivariable regression analyses to test for associations between frequency of
      cooking dinner at home and factors of interest. SETTING: The 2007-2008 National
      Health and Nutrition Examination Survey (NHANES). SUBJECTS: The sample consisted
      of 10 149 participants. RESULTS: Americans reported cooking an average of five
      dinners per week; 8 % never, 43 % sometimes and 49 % always cooked dinner at
      home. Lower household wealth and educational attainment were associated with a
      higher likelihood of either always or never cooking dinner at home, whereas
      wealthier, more educated households were more likely to sometimes cook dinner at
      home (P < 0.05). Black households cooked the fewest dinners at home (mean = 4.4,
      95 % CI 4.2, 4.6). Households with foreign-born reference persons cooked more
      dinners at home (mean = 5.8, 95 % CI 5.7, 6.0) than households with US-born
      reference persons (mean = 4.9, 95 % CI 4.7, 5.1). Households with dependants
      cooked more dinners at home (mean = 5.2, 95 % CI 5.1, 5.4) than households
      without dependants (mean = 4.6, 95 % CI 4.3, 5.0). CONCLUSIONS: Home dinner
      preparation habits varied substantially with socio-economic status and
      race/ethnicity, associations that likely will have implications for designing and
      appropriately tailoring interventions to improve home food preparation practices
      and promote healthy eating.

PMID- 24107576
TI  - Nicotine dependence produces hyperalgesia: role of corticotropin-releasing factor
      1 receptors (CRF1Rs) in the central amygdala (CeA).
AB  - Because tobacco use has a large negative health and financial impact on society,
      it is critical to identify the factors that drive excessive use. These factors
      include the aversive withdrawal symptoms that manifest upon cessation of tobacco
      use, and may include increases in nociceptive processing. Corticotropin-releasing
      factor (CRF) signalling in the central amygdala (CeA) has been attributed an
      important role in: (1) central processing of pain, (2) excessive nicotine use
      that results in nicotine dependence, and (3) in mediating the aversive symptoms
      that manifest following cessation of tobacco exposure. Here, we describe three
      experiments in which the main hypothesis was that CRF/CRF1 receptor (CRF1R)
      signalling in the CeA mediates nicotine withdrawal-induced increases in
      nociceptive sensitivity in rats that are dependent on nicotine. In Experiment 1,
      nicotine-dependent rats withdrawn from chronic intermittent (14-h/day) nicotine
      vapor exhibited decreased hind paw withdrawal latencies in response to a painful
      thermal stimulus in the Hargreaves test, and this effect was attenuated by
      systemic administration of the CRF1R antagonist, R121919. In Experiment 2,
      nicotine-dependent rats withdrawn from nicotine vapor exhibited robust increases
      in mRNA for CRF and CRF1Rs in CeA. In Experiment 3, intra-CeA administration of
      R121919 reduced thermal nociception only in nicotine-dependent rats.
      Collectively, these results suggest that nicotine dependence increases CRF/CRF1R
      signalling in the CeA that mediates withdrawal-induced increases in sensitivity
      to a painful stimulus. Future studies will build on these findings by exploring
      the hypothesis that nicotine withdrawal-induced reduction in pain thresholds
      drive excessive nicotine use via CRF/CRF1R signalling pathways. 

PMID- 24107578
TI  - Dying at home: a qualitative study of the perspectives of older South Asians
      living in the United Kingdom.
AB  - BACKGROUND: South Asians constitute the single largest ethnic minority group in
      the United Kingdom, yet little is known about their perspectives on, and
      experiences of, end-of-life care. AIM: To explore beliefs, attitudes and
      expectations expressed by older South Asians living in East London about dying at
      home. DESIGN: A qualitative study using focus groups and semi-structured
      interviews. Data were analysed using a constructivist grounded theory approach.
      SETTING/PARTICIPANTS: Five focus groups and 29 in-depth semi-structured
      interviews were conducted with a total of 55 older adults (24 men and 31 women)
      aged between 52 and 78 years. Participants from six South Asian ethnic groups
      were recruited via 11 local community organisations. RESULTS: Two key themes were
      identified. The theme of 'reconsidering the homeland' draws on the notion of
      'diaspora' to help understand why for many participants, the physical place of
      death was perceived as less important than the opportunity to carry out cultural
      and religious practices surrounding death. The second theme 'home as a haven'
      describes participants' accounts of how their home is a place in which it is
      possible to perform various cultural and religious rituals. Cultural and
      religious practices were often seen as essential to achieving a peaceful death
      and honouring religious and filial duties. CONCLUSIONS: Older people of South
      Asian ethnicity living in East London perceive home as more than a physical
      location for dying relatives. They make efforts to adhere, and also adapt, to
      important social and cultural values relating to death and dying as part of the
      wider challenge of living in an emigrant society.

PMID- 24107580
TI  - A fossil Fuchsia (Onagraceae) flower and an anther mass with in situ pollen from
      the early Miocene of New Zealand.
AB  - PREMISE OF THE STUDY: Fuchsia (Onagraceae) anthers, pollen, and an
      ornithophilous Fuchsia-like flower from an earliest Miocene lacustrine diatomite
      deposit at Foulden Maar, southern New Zealand confirm a long record for Fuchsia
      in New Zealand and probably an equally long history for its distinctive
      honeyeater pollination syndrome. The anthers contain in situ pollen of the fossil
      palynomorph previously assigned to Diporites aspis Pocknall et Mildenh.
      (Onagraceae: Fuchsia L.). * METHODS: We undertook comparative studies of the
      flower and anther morphology of the newly discovered macrofossils and compared
      the in situ pollen grains from the anthers with dispersed pollen grains from
      extant species. * KEY RESULTS: The anther mass is referred to a new, extinct
      species, Fuchsia antiqua D.E.Lee, Conran, Bannister, U.Kaulfuss & Mildenh.
      (Onagraceae), and is associated with a fossilized Fuchsia-like flower from the
      same small mining pit. Because Diporites van der Hammen is typified by a fungal
      sporomorph, the replacement name for D. aspis is Koninidites aspis (Pocknall &
      Mildenh.) Mildenh. gen. & comb. nov. Phylogenetic placement of the fossils agrees
      with a proximal position to either sect. Skinnera or sect. Procumbentes. These
      are the oldest macrofossils of Fuchsia globally. * CONCLUSIONS: The floral
      structures are remarkably similar to those of modern New Zealand Fuchsia. They
      suggest that the distinctive honeyeater bird-pollination syndrome/association
      seen in modern New Zealand was already established by the late Oligocene-earliest
      Miocene. The implications for the biogeography and paleoecology of Fuchsia in
      Australasia are discussed.

PMID- 24107581
TI  - Phenotypic plasticity and differentiation in fitness-related traits in invasive
      populations of the Mediterranean forb Centaurea melitensis (Asteraceae).
AB  - PREMISE OF THE STUDY: Biological invasions threaten global biodiversity,
      resulting in severe ecological and economic costs. Phenotypic plasticity and
      differentiation in fitness-related traits after introduction can contribute to
      increased performance in invasive populations of plants. We determined whether
      postintroduction evolution in trait means or in their plasticity, or inherent
      species-wide phenotypic plasticity has promoted invasiveness in a European annual
      forb. * METHODS: In a common greenhouse, we compared several fitness-related
      traits and the phenotypic plasticity of those traits under four levels of
      nutrients among native and invasive populations of Centaurea melitensis. We
      tested 18 populations from three regions of similar mediterranean climate type:
      the native range (southern Spain) and two invaded ranges (California and central
      Chile). * KEY RESULTS: Centaurea melitensis possesses overall phenotypic
      plasticity, which is a trait that promotes invasiveness. Invasive populations
      were differentiated from native plants for several trait means and their levels
      of phenotypic plasticity in directions that enhance competitive ability and
      success. Invasive plants flowered earlier and grew faster in the early stages of
      growth phases, important features for invasiveness. * CONCLUSIONS: Phenotypic
      plasticity, its evolution postinvasion, and the evolution of fitness-related
      trait means in invasive populations have potentially contributed to the invasion
      of C. melitensis in California and Chile. Along with an overall wide range of
      tolerance to growing conditions, C. meltiensis populations that have colonized
      habitats in California and Chile have undergone rapid evolution in several life
      history traits and the plasticities of those traits in directions that would
      promote invasiveness in mediterranean ecosystems.

PMID- 24107579
TI  - Physical performance and frailty in chronic kidney disease.
AB  - BACKGROUND: Poor physical performance and frailty are associated with elevated
      risks of death and disability. Chronic kidney disease (CKD) is also strongly
      associated with these outcomes. The risks of poor physical performance and
      frailty among CKD patients, however, are not well established. METHODS: We
      measured the Short Physical Performance Battery (SPPB; a summary test of gait
      speed, chair raises and balance; range 0-12) and the five elements of frailty
      among 1,111 Chronic Renal Insufficiency Cohort participants. Adjusting for
      demographics and multiple comorbidities, we fit a linear regression model for the
      outcome of SPPB score and an ordinal logistic regression model for frailty
      status. RESULTS: Median (interquartile range, IQR) age was 65 (57-71) years,
      median estimated glomerular filtration rate (eGFR) for non-dialysis patients was
      49 (36-62) ml/min/1.73 m(2), and median SPPB score was 9 (7-10). Seven percent of
      participants were frail and 43% were pre-frail. Compared with the SPPB score for
      eGFR >60 ml/min/1.73 m(2), the SPPB was 0.51 points lower for eGFR 30-59; 0.61
      points lower for eGFR 15-29, and 1.75 points lower for eGFR <15 (p < 0.01 for all
      comparisons). eGFR 30-59 (odds ratio, OR 1.45; p = 0.024), eGFR 15-29 (OR 2.02; p
      = 0.002) and eGFR <15 (OR 4.83; p < 0.001) were associated with worse frailty
      status compared with eGFR >60 ml/min/1.73 m(2). CONCLUSIONS: CKD severity was
      associated with poor physical performance and frailty in a graded fashion. Future
      trials should determine if outcomes for CKD patients with frailty and poor
      physical performance are improved by targeted interventions.

PMID- 24107582
TI  - Phylogenetic relationships among the North American cleomoids (Cleomaceae): a
      test of Iltis's reduction series.
AB  - PREMISE OF STUDY: A monophyletic group composed of five genera of the Cleomaceae
      represents an intriguing lineage with outstanding taxonomic and evolutionary
      questions. Generic boundaries are poorly defined, and historical hypotheses
      regarding the evolution of fruit type and phylogenetic relationships provide
      testable questions. This is the first detailed phylogenetic investigation of all
      22 species in this group. We use this phylogenetic framework to assess generic
      monophyly and test Iltis's evolutionary "reduction series" hypothesis regarding
      phylogeny and fruit type/seed number. * METHODS: Maximum likelihood and Bayesian
      analyses of four plastid intergenic spacer region sequences (rpl32-trnL, trnQ
      rps16, ycf1-rps15, and psbA-trnH) and one nuclear (ITS) region were used to
      reconstruct phylogenetic relationships among the NA cleomoid species. Stochastic
      mapping and ancestral-state reconstruction were used to study the evolution of
      fruit type. * KEY RESULTS: Both analyses recovered nearly identical phylogenies.
      Three of the currently recognized genera (Wislizenia, Carsonia, and Oxystylis)
      are monophyletic while two (Cleomella and Peritoma) are para- or polyphyletic.
      There was a single origin of the two-seeded schizocarp in the ancestor of the
      Oxystylis-Wislizenia clade and a secondary derivation of elongated capsule-type
      fruits in Peritoma from a truncated capsule state in Cleomella. * CONCLUSIONS:
      Our well-resolved phylogeny supports most of the current species circumscriptions
      but not current generic circumscriptions. Additionally, our results are
      inconsistent with Iltis's hypothesis of species with elongated many-seed fruits
      giving rise to species with truncated few-seeded fruits. Instead, we find support
      for the reversion to elongated multiseeded fruits from a truncate few-seeded
      ancestor in Peritoma.

PMID- 24107583
TI  - Exploring variation in leaf mass per area (LMA) from leaf to cell: an anatomical
      analysis of 26 woody species.
AB  - PREMISE OF THE STUDY: Plant species differ widely in the leaf biomass invested
      per unit area (LMA). LMA can be explained by variation in leaf thickness and/or
      density, both of which are influenced by anatomical tissue composition. The aim
      of this study is to quantify the anatomical characteristics that underlie
      variation in LMA in a range of woody species. * METHODS: Twenty-six woody
      species, forming 13 species pairs with a deciduous and evergreen species from the
      same genus or family, were grown in a glasshouse. The youngest full-grown leaves
      were analyzed for LMA and morpho-anatomical characteristics at leaf, tissue, and
      cell level. * KEY RESULTS: Considered over all species studied, leaf thickness
      and density were equally important to explain the variation in LMA, but the class
      difference between deciduous and evergreen species was mainly determined by
      thickness, whereas variation within each group was largely due to density.
      Evergreens had thicker leaves, predominantly caused by a larger volume of
      mesophyll and air spaces, whereas the higher leaf density within each group was
      due to a lower proportion of epidermis and air spaces, and overall smaller cells.
      * CONCLUSIONS: The anatomical basis for variation in LMA in woody species depends
      on the contrast made. Higher LMA in evergreens is mainly due to a greater leaf
      thickness, caused by a larger volume of mesophyll and air spaces. Within
      deciduous species and evergreens, higher LMA is caused by a higher density, due
      to higher volumetric fractions of mesophyll and lower fractions of air spaces and
      epidermis.

PMID- 24107584
TI  - Survival of a tertiary relict species, Liriodendron chinense (Magnoliaceae), in
      southern China, with special reference to village fengshui forests.
AB  - PREMISE OF THE STUDY: We investigate factors supporting the persistence in
      southern China of a rare Tertiary relict tree species, Liriodendron chinense,
      which has been almost eliminated by recent land use conversion. We hypothesize
      that cultural practices and traditional sustainable forest resource uses provide
      niches for the species' regeneration that will complement infrequent natural
      disturbances, while the species' survival on remote mountain slopes where there
      are no humans depends on natural disturbances alone. * METHODS: We examined and
      analyzed various landscape contexts, community associations, age distributions,
      and regeneration patterns of Liriodendron chinense. * KEY RESULTS: Forest
      communities containing Liriodendron chinense were of three types: (1) village
      fengshui forests-mature forests dominated by Tertiary relict taxa Liriodendron,
      Toona, and Emmenopterys, protected for their supposed spiritual value; (2) young
      secondary forests near villages, dominated solely by Liriodendron; and (3) old
      secondary forest remnants on mountain slopes far from villages, dominated by
      Liriodendron with other Tertiary relicts of the genera Davidia and Sassafras. The
      age structure of Liriodendron indicated ample recruitment in the first two forest
      types, where the activities of local people have provided regeneration niches for
      the survival of this shade-intolerant pioneer species. On the remote mountain
      slopes that have never been converted to agriculture, Liriodendron has survived
      through regeneration made possible by natural disturbances. * CONCLUSIONS: The
      traditional human land use, influenced by cultural values, has supplemented
      infrequent natural disturbances, providing regeneration niches for this and other
      Tertiary remnant species near villages in mountain valleys, while on uninhabited
      mountain slopes the species depends on natural disturbances to survive.

PMID- 24107585
TI  - The average culling rate of Dutch dairy herds over the years 2007 to 2010 and its
      association with herd reproduction, performance and health.
AB  - Optimising the number of replacement heifers needed will have positive economic
      and environmental consequences on herds that rear their own young stock. The
      number of heifers needed to be kept is closely related with the number of culled
      dairy cows in the herd. This study therefore looked at the variation that exists
      in culling rate and herd level factors associated with it. A dataset from 1903
      dairy herds available included information at animal level (dates of culling,
      slaughter/death) and herd level (characteristics of reproduction, performance,
      health) over the years 2007 to 2010. The average culling rate for slaughter/death
      was used and was defined for each year as percentage of the herd size that died
      within 30 d after they were culled. The analysis of the association between
      average culling rate for slaughter/death and the characteristics of the herd was
      performed using a mixed model. The results showed that the average culling rate
      for slaughter/death was 25.4% and varied between 23% (2007) and 28% (2010). More
      than 70% of the herds have an average culling rate for slaughter/death of less
      than 30%, showing that there is room for lowering the average culling rate for
      slaughter/death. A higher average culling rate for slaughter/death is associated
      with a longer average calving interval, a higher average 305-d protein
      production, a higher average somatic cell count (SCC), a higher percentage of new
      high SCC, a more than 5% decrease in herd size, and herds that bought more than
      1% of animals per year. A lower average culling rate for slaughter/death is
      associated with a longer average age, herds that bought less than 1% of animals
      per year and a more than 5% increase in herd size. In conclusion, the average
      culling rate for slaughter/death is associated with fertility, udder health and
      openness of the herd. 

PMID- 24107586
TI  - Effects of 8 weeks of Xpand(r) 2X pre workout supplementation on skeletal muscle
      hypertrophy, lean body mass, and strength in resistance trained males.
AB  - BACKGROUND: Xpand(r) 2X is a proprietary blend comprised of branched chain amino
      acids, creatine monohydrate, beta-alanine (CarnoSyn(r)), quercetin, coenzymated B
      vitamins, alanyl-glutamine (Sustamine(r)), and natural nitrate sources from
      pomegranate and beet root extracts purported to enhance the neuromuscular
      adaptations of resistance training. However to date, no long-term studies have
      been conducted with this supplement. The purpose of this study was to investigate
      the effects of a multi-ingredient performance supplement (MIPS) on skeletal
      muscle hypertrophy, lean body mass and lower body strength in resistance-trained
      males. METHODS: Twenty resistance-trained males (21.3 +/- 1.9 years) were
      randomly assigned to consume a MIPS or a placebo of equal weight and volume (food
      grade orange flavors and sweeteners) in a double-blind manner, 30 minutes prior
      to exercise. All subjects participated in an 8-week, 3-day per week, periodized,
      resistance-training program that was split-focused on multi-joint movements such
      as leg press, bench press, and bent-over rows. Ultrasonography measured muscle
      thickness of the quadriceps, dual-energy X-ray absorptiometry (DEXA) determined
      lean body mass, and strength of the bench press and leg press were determined at
      weeks 0, 4, and 8 of the study. Data were analyzed with a 2 * 3 repeated measures
      ANOVA with LSD post hoc tests utilized to locate differences. RESULTS: There was
      a significant group-by-time interaction in which the MIPS supplementation
      resulted in a significant (p < 0.01) increase in strength of the bench press
      (18.4% vs. 9.6%) compared with placebo after 4 and 8 weeks of training. There
      were no significant group by time interactions between MIPS supplementation nor
      the placebo in leg press strength (p = .08). MIPS supplementation also resulted
      in a significant increase in lean body mass (7.8% vs. 3.6%) and quadriceps muscle
      thickness (11.8% vs. 4.5%) compared with placebo (group*time, p <0.01).
      CONCLUSIONS: These results suggest that this MIPS can positively augment
      adaptations in strength, and skeletal muscle hypertrophy in resistance-trained
      men.

PMID- 24107587
TI  - Mediterranean and DASH diet scores and mortality in women with heart failure: The
      Women's Health Initiative.
AB  - BACKGROUND: Current dietary recommendations for patients with heart failure (HF)
      are largely based on data from non-HF populations; evidence on associations of
      dietary patterns with outcomes in HF is limited. We therefore evaluated
      associations of Mediterranean and Dietary Approaches to Stop Hypertension (DASH)
      diet scores with mortality among postmenopausal women with HF. METHODS AND
      RESULTS: Women's Health Initiative participants were followed up from the date of
      HF hospitalization through the date of death or last participant contact before
      August 2009. Mediterranean and DASH diet scores were calculated from food
      frequency questionnaires. Cox proportional hazards models adjusted for
      demographics, health behaviors, and health status were used to calculate hazard
      ratios and 95% confidence intervals (CI). For a median of 4.6 years of follow-up,
      1385 of 3215 (43.1%) participants who experienced a HF hospitalization died.
      Multivariable-adjusted hazard ratios were 1 (reference), 1.05 (95% CI, 0.89
      1.24), 0.97 (95% CI, 0.81-1.17), and 0.85 (95% CI, 0.70-1.02) across quartiles of
      the Mediterranean diet score (P trend=0.08) and 1 (reference), 1.04 (95% CI, 0.89
      1.21), 0.83 (95% CI, 0.70-0.98), and 0.84 (95% CI, 0.70-1.00) across quartiles of
      the DASH diet score (P trend=0.01). Diet score components, vegetables, nuts, and
      whole grain intake, were inversely associated with mortality. CONCLUSIONS: Higher
      DASH diet scores were associated with modestly lower mortality in women with HF,
      and there was a nonsignificant trend toward an inverse association with
      Mediterranean diet scores. These data provide support for the concept that
      dietary recommendations developed for other cardiovascular conditions or general
      populations may also be appropriate in patients with HF. CLINICAL TRIAL
      REGISTRATION: URL: http://www.clinicaltrials.gov. Unique identifier: NCT00000611.

PMID- 24107589
TI  - Significance of binucleated cells with compression in atypical squamous cells of
      undetermined significance.
AB  - OBJECTIVE: To increase the accuracy of the diagnosis of atypical squamous cells
      of undetermined significance (ASC-US), ASC-US were divided into high-risk human
      papillomavirus (HPV HR+) and non-high-risk HPV (HPV HR-) cases to analyze the
      significance of binucleated cells with compression. STUDY DESIGN: ThinPrep
      specimens of ASC-US were examined. This study included 21 CIN and HPV HR+ (CIN+),
      19 benign and HPV HR- (B-) and 10 benign and HPV HR+ (B+) cases. The number of
      cells were examined by defining binucleated cells with their nuclei pressing
      against each other as positive compression, and their relation to the relative
      light units (RLUs) of the DNA Hybrid capture 2 (HC2) was determined. RESULTS:
      95.2% of CIN+ and 15.8% of B- cases were compression positive, while 4.8% of CIN+
      and 84.2% of B- cases were compression negative, which was significantly
      different. The average number of cells with positive compression was 5.7 +/- 5.3
      in CIN+, 2.0 +/- 0.7 in B- and 5.5 +/- 1.5 in B+ cases, with significant
      differences between CIN+ and B- and between B- and B+ cases. The number of
      compression-positive cells increased as HPV HC2 RLUs became higher. CONCLUSION:
      Positive compression is useful in determining ASC-US with HPV HR+. The
      identification of positive compression is highly practical because it can be
      observed morphologically.

PMID- 24107588
TI  - Nitroxyl (HNO): A novel approach for the acute treatment of heart failure.
AB  - BACKGROUND: The nitroxyl (HNO) donor, Angeli's salt, exerts positive inotropic,
      lusitropic, and vasodilator effects in vivo that are cAMP independent. Its
      clinical usefulness is limited by chemical instability and cogeneration of
      nitrite which itself has vascular effects. Here, we report on effects of a novel,
      stable, pure HNO donor (CXL-1020) in isolated myoctyes and intact hearts in
      experimental models and in patients with heart failure (HF). METHODS AND RESULTS:
      CXL-1020 converts solely to HNO and inactive CXL-1051 with a t1/2 of 2 minutes.
      In adult mouse ventricular myocytes, it dose dependently increased sarcomere
      shortening by 75% to 210% (50-500 MUmol/L), with a ~30% rise in the peak Ca(2+)
      transient only at higher doses. Neither inhibition of protein kinase A nor
      soluble guanylate cyclase altered this contractile response. Unlike
      isoproterenol, CXL-1020 was equally effective in myocytes from normal or failing
      hearts. In anesthetized dogs with coronary microembolization-induced HF, CXL-1020
      reduced left ventricular end-diastolic pressure and myocardial oxygen consumption
      while increasing ejection fraction from 27% to 40% and maximal ventricular power
      index by 42% (both P<0.05). In conscious dogs with tachypacing-induced HF, CXL
      1020 increased contractility assessed by end-systolic elastance and provided
      venoarterial dilation. Heart rate was minimally altered. In patients with
      systolic HF, CXL-1020 reduced both left and right heart filling pressures and
      systemic vascular resistance, while increasing cardiac and stroke volume index.
      Heart rate was unchanged, and arterial pressure declined modestly. CONCLUSIONS:
      These data show the functional efficacy of a novel pure HNO donor to enhance
      myocardial function and present first-in-man evidence for its potential
      usefulness in HF. CLINICAL TRIAL REGISTRATION: URL:
      http://www.clinicaltrials.gov. Unique identifiers: NCT01096043, NCT01092325.

PMID- 24107590
TI  - Development and validation of a rapid, generic measure of disease control from
      the patient's perspective: the IBD-control questionnaire.
AB  - INTRODUCTION: The use of patient reported outcome measures to support routine
      inflammatory bowel disease (IBD) care is not widespread and suggests that
      existing questionnaires lack relevance to day-to-day decisions or are too
      cumbersome to administer. We developed a simple, generic tool for capturing
      disease control from the patient's perspective to address these barriers.
      METHODS: Development based on literature review, patient focus groups/interviews
      and a steering group, defining a limited set of generic questions. The 'IBD
      Control' questionnaire comprises 13 items plus a visual analogue scale (VAS) (0
      100). Prospective validation involved baseline completion of IBD-Control, quality
      of life (QoL) questionnaire (UK-IBD-Q), EuroQol (EQ-5D), Hospital Anxiety and
      Depression Score; and clinician assessment (blinded to questionnaire; recording
      Harvey-Bradshaw Index or Simple Clinical Colitis Activity Index; Global Clinician
      Rating; treatment outcome). RESULTS: 299 patients returned baseline surveys
      (Crohn's disease, n=160; ulcerative colitis, n=139) and 138 attended for repeat
      visits. Completion time (mean; SD): 1 min 15 s; 25 s; Internal consistency:
      Cronbach's alpha for all 13 items (0.85); for subgroup of eight questions ('IBD
      Control-8'; 0.86). Strong correlation between IBD-Control-8 and IBD-Control-VAS
      (r=0.81). Test-retest reliability (2 week repeat): intra-class correlation=0.97
      for IBD-Control-8 and 0.96 for IBD-Control-VAS. Construct validity: Moderate-to
      strong correlations between IBD-Control-8 and IBD-Control-VAS versus activity
      indices, UK-IBD-Q and EQ-5D (utility) with r values 0.52-0.86. Discriminant
      validity (mean instrument scores for remission, mild, moderate or severe):
      p<0.001 (analysis of variance (ANOVA)). Sensitivity to change: Effect sizes: 0.76
      1.44. CONCLUSIONS: The IBD-Control is a rapid, reliable, valid and sensitive
      instrument for measuring overall disease control from the patient's perspective.
      Unlike existing patient reported outcome measures, its simplicity, ease-of-use
      and generic applicability make it a candidate for supporting routine care.

PMID- 24107592
TI  - Characterization of small-field stereotactic radiosurgery beams with modern
      detectors.
AB  - To derive accurate beam models for stereotactic radiosurgery (SRS) planning it is
      necessary to characterize the beam with dosimetric measurements. The aim of this
      study is to identify the best detectors for each task in the characterization
      process. Output ratios, beam profiles and percentage depth doses were measured
      for SRS cone diameters of 5-45 mm. Commercially available and emerging detectors
      were used: Gafchromic EBT2 film, an air-core fibre optic dosimeter (FOD)
      (developed at Royal Prince Alfred Hospital, Sydney), an IBA stereotactic field
      diode, a PTW 60012 electron diode and an IBA cc01 small volume thimble ion
      chamber. Analysis of the measured data supported by baseline Monte Carlo
      simulation data, led to the following recommendations: (1) water-equivalent
      detectors (Gafchromic EBT2 film or FOD) are the preferred choice for SRS
      dosimetry, (2) ion chambers (including small volume chambers with high-density
      central electrodes) should be avoided due to volume averaging effects and energy
      dependence, (3) if diodes are used, corrections must be made to account for their
      over-response in small fields. 

PMID- 24107591
TI  - Duodenal nutrient exclusion improves metabolic syndrome and stimulates villus
      hyperplasia.
AB  - OBJECTIVE: Surgical interventions that prevent nutrient exposure to the duodenum
      are among the most successful treatments for obesity and diabetes. However, these
      interventions are highly invasive, irreversible and often carry significant risk.
      The duodenal-endoluminal sleeve (DES) is a flexible tube that acts as a barrier
      to nutrient-tissue interaction along the duodenum. We implanted this device in
      Zucker Diabetic Fatty (ZDF) rats to gain greater understanding of duodenal
      nutrient exclusion on glucose homeostasis. DESIGN: ZDF rats were randomised to
      four groups: Naive, sham ad libitum, sham pair-fed, and DES implanted. Food
      intake, body weight (BW) and body composition were measured for 28 days
      postoperatively. Glucose, lipid and bile acid metabolism were evaluated, as well
      as histological assessment of the upper intestine. RESULTS: DES implantation
      induced a sustained decrease in BW throughout the study that was matched by pair
      fed sham animals. Decreased BW resulted from loss of fat, but not lean mass. DES
      rats were also found to be more glucose tolerant than either ad libitum-fed or
      pair-fed sham controls, suggesting fat mass independent metabolic benefits. DES
      also reduced circulating triglyceride and glycerol levels while increasing
      circulating bile acids. Interestingly, DES stimulated a considerable increase in
      villus length throughout the upper intestine, which may contribute to metabolic
      improvements. CONCLUSIONS: Our preclinical results validate DES as a promising
      therapeutic approach to diabetes and obesity, which offers reversibility, low
      risk, low invasiveness and triple benefits including fat mass loss, glucose and
      lipid metabolism improvement which mechanistically may involve increased villus
      growth in the upper gut.

PMID- 24107594
TI  - Lacidipine attenuates apoptosis via a caspase-3 dependent pathway in human kidney
      cells.
AB  - BACKGROUND: Acute kidney injury (AKI) is common in hospitalised patients and has
      a poor prognosis. Therefore, new therapeutic strategies are anticipated.
      Lacidipine, a novel third-generation dihydropyridine calcium channel blocker, has
      been demonstrated effective for hypertension. However, its potential effect on
      renal injury remains unknown. In the present study, an in vitro model of renal
      ischemia reperfusion (I/R) injury was used to investigate the protective effect
      and underlying mechanisms of lacidipine on human kidney cell (HKC) apoptosis.
      METHODS: HKCs were subjected to adenosine triphosphate (ATP) depletion and
      recovery (0.01 uM AA, depletion for 2 h and recovery for 30 min), with or without
      lacidipine (1 uM and 10 uM, 24 h), then cell viability and apoptosis were
      determined using the cell counting kit-8 (CCK-8) assay and Annexin V flow
      cytometry. The expression of Bcl-2, Bax, and cytochrome c (cyt c) was examined by
      western blot. RESULTS: Antimycin A (AA) was found to induce apoptosis of HKCs.
      The proportion of early apoptosis and activity of caspase-3 peaked at 30 min
      after ATP depletion and recovery and were attenuated by lacidipine. The
      expression of cyt c and Bax was decreased, while that of Bcl-2 was increased
      significantly in lacidipine treated group. CONCLUSION: We conclude that
      lacidipine protects HKCs against apoptosis induced by ATP depletion and recovery
      by regulating the caspase-3 pathway.

PMID- 24107593
TI  - Prevalence and predictors of exclusive breastfeeding among women in Kilimanjaro
      region, Northern Tanzania: a population based cross-sectional study.
AB  - BACKGROUND: Exclusive breastfeeding (EBF) is a simple and cost-effective
      intervention to improve child health and survival. Effective EBF has been
      estimated to avert 13% - 15% of under-five mortality and contribute to reduce
      mother to child transmission of HIV. The prevalence of EBF for infant less than
      six months is low in most developing countries, including Tanzania (50%). While
      the Tanzania Demographic Health Survey collects information on overall EBF
      prevalence, it does not evaluate factors influencing EBF. The aim of this paper
      was to determine the prevalence and predictors of exclusive breastfeeding in
      urban and rural areas in Kilimanjaro region. METHODS: A population-based cross
      sectional study was conducted between June 2010 to March 2011 among women with
      infants aged 6-12 months in Kilimanjaro. Multi-stage proportionate to size
      sampling was used to select participants from all the seven districts of the
      region. A standardized questionnaire was used to collect socio-demographic,
      reproductive, alcohol intake, breastfeeding patterns and nutritional data during
      the interviews. Estimation on EBF was based on recall since birth. Multivariable
      logistic regression was used to obtain independent predictors of EBF. RESULTS: A
      total of 624 women participated, 77% (483) from rural areas. The prevalence of
      EBF up to six months in Kilimanjaro region was 20.7%, without significant
      differences in the prevalence of EBF up to six months between urban (22.7%) and
      rural areas (20.1%); (OR = 0.7, 95% CI 0.5,1.4).In multivariable analysis, advice
      on breastfeeding after delivery (Adjusted odds ratio, AOR = 2.6, 95% CI 1.5, 4.6)
      was positively associated with EBF up to six months. Compared to
      married/cohabiting and those who do not take alcohol, single mothers (AOR = 0.4,
      95% CI 0.2, 0.9) and mothers who drank alcohol (AOR = 0.4, 95% CI 0.3, 0.7) had
      less odds to practice EBF up to six months. CONCLUSION: Prevalence of EBF up to
      six months is still low in Kilimanjaro, lower than the national coverage of 50%.
      Strengthening of EBF counseling in all reproductive and child health clinics
      especially during antenatal and postnatal periods may help to improve EBF rates.

PMID- 24107595
TI  - Efficacy of fractional microneedle radiofrequency device in the treatment of
      primary axillary hyperhidrosis: a pilot study.
AB  - BACKGROUND: Fractional microneedle radiofrequency (FMR) devices deliver energy to
      the deep dermis through insulated microneedles without destroying the epidermis.
      These FMR devices have been shown to be effective for the treatment of wrinkles,
      acne scars and large pores. In this study it was postulated that FMR energy could
      specifically affect the sweat glands, preserving the skin surface even if sweat
      glands were seated in the deep dermis. OBJECTIVE: To evaluate the efficacy and
      safety of FMR for primary axillary hyperhidrosis (PAH) treatment and to conduct a
      histological analysis before and after treatment. METHODS: Twenty patients with
      PAH had 2 sessions of bipolar FMR treatment at 4-week intervals. Clinical
      improvement was evaluated using a Hyperhidrosis Disease Severity Scale (HDSS) and
      photographs were taken using the starch-iodine test at every visit and 2 months
      after the last treatment. The amount of sweat reduction was indirectly assessed
      using a TewameterTM. Skin biopsies were obtained from 3 of the enrolled patients
      before and after treatment. The satisfaction and adverse reactions of the
      research participants were recorded at every follow-up visit. RESULTS: HDSS
      scores decreased significantly from a baseline of 3.3 to 1.5 and 1.8 after the
      first and second months of posttreatment follow-up sessions, respectively (p <
      0.001). In response to a subjective assessment at 1 month after the second
      treatment, 75% of patients (n = 15) had an HDSS score of 1 or 2, and 70% of
      patients (n = 14) expressed more than 50% improvement in their sweating. The
      starch-iodine reaction was also remarkably reduced in 95% of patients (n = 19)
      after FMR treatment. Histological findings showed a decrease in the number and
      size of both apocrine and eccrine glands 1 month after the final treatment. Side
      effects were minimal and included mild discomfort, transient swelling and
      postinflammatory hyperpigmentation. CONCLUSION: FMR treatment was effective for
      the treatment of PAH without significant adverse reactions due to direct
      volumetric heating of the lower dermis.

PMID- 24107596
TI  - Resveratrol inhibits hydrogen peroxide-induced apoptosis in endothelial cells via
      the activation of PI3K/Akt by miR-126.
AB  - AIM: Resveratrol(RSV) is an edible polyphenolic phytoalexin present in different
      plant species that plays an important role in improving endothelial dysfunction.
      However, the molecular mechanisms underlying these effects are unknown. In the
      present study, the mechanism underlying the protection of CRL-1730 cells by RSV
      against oxidative stress was examined. METHODS: We first assessed the effects of
      RSV on the cell viability and apoptosis of CRL-1730 cells exposed to hydrogen
      peroxide(H2O2). Real-time PCR was used to determine the microRNA-126(miR-126)
      expression in cells treated with RSV and/or H2O2. We also evaluated the PI3K/Akt
      signaling pathway in CRL-1730 cells following upregulation of the miR-126
      expression. Finally, we determined the effects of miR-126 on RSV against
      oxidative injury using an miR-126 inhibitor. RESULTS: Treatment with RSV resulted
      in a significant increase in survival and a decrease in the apoptosis of CRL-1730
      cells exposed to H2O2. We also found that H2O2 significantly suppressed the
      expression of miR-126, which was reversed by RSV in a dose-dependent manner. The
      overexpression of miR-126 decreased PIK3R2(p85-beta) and enhanced Akt
      phosphorylation, which resulted in an increase in the survival of CRL-1730 cells
      exposed to H2O2. More importantly, the downregulation of the miR-126 expression
      reversed the effects of RSV on the survival and apoptosis of CRL-1730 cells
      exposed to H2O2. In addition, the knockdown of Ets-1 reversed the effects of RSV
      on the miR-126 expression in CRL-1730 cells exposed to H2O2. CONCLUSIONS: In this
      study, we demonstrated that the protection of endothelial cells by RSV against
      oxidative injury is due to the activation of PI3K/Akt by miR-126.

PMID- 24107597
TI  - Brain levels of the neurotoxic pyridinium metabolite HPP+ and extrapyramidal
      symptoms in haloperidol-treated mice.
AB  - The typical antipsychotic haloperidol is a highly effective treatment for
      schizophrenia but its use is limited by a number of serious, and often
      irreversible, motor side effects. These adverse drug reactions, termed
      extrapyramidal syndromes (EPS), result from an unknown pathophysiological
      mechanism. One theory relates to the observation that the haloperidol metabolite
      HPP+ (4-(4-chlorophenyl)-1-[4-(4-fluorophenyl)-4-oxobutyl]-pyridinium) is
      structurally similar to MPP+ (1-methyl-4-phenylpyridinium), a neurotoxin
      responsible for an irreversible neurodegenerative condition similar to
      Parkinson's disease. To determine whether HPP+ contributes to haloperidol-induced
      EPS, we measured brain HPP+ and haloperidol levels in strains of mice at high
      (C57BL/6J and NZO/HILtJ) and low (BALB/cByJ and PWK/PhJ) liability to haloperidol
      induced EPS following chronic treatment (7-10 adult male mice per strain). Brain
      levels of HPP+ and the ratio of HPP+ to haloperidol were not significantly
      different between the haloperidol-sensitive and haloperidol-resistant strain
      groups (P=0.50). Within each group, however, strain differences were seen
      (P<0.01), indicating that genetic variation regulating steady-state HPP+ levels
      exists. Since the HPP+ levels that we observed in mouse brain overlap the range
      of those detected in post-mortem human brains following chronic haloperidol
      treatment, the findings from this study are physiologically relevant to humans.
      The results suggest that strain differences in steady-state HPP+ levels do not
      explain sensitivity to haloperidol-induced EPS in the mice we studied. 

PMID- 24107598
TI  - Endovascular treatment of intracranial aneurysms with detachable coils:
      correlation between aneurysm volume, packing, and angiographic recurrence.
AB  - BACKGROUND AND PURPOSE: The relationship between dense packing and incidence of
      angiographic recurrence after endovascular treatment of intracranial aneurysms
      has been shown but remains controversial. We retrospectively analyzed
      intracranial aneurysms treated with detachable coils to determine the relation
      between aneurysm volume, packing, and recurrence. METHODS: We reviewed 221
      aneurysms in 199 patients who underwent endovascular coiling using detachable
      coils from November 2009 to December 2011. Aneurysm volumes were determined using
      three-dimensional images obtained from rotational angiography. Aneurysm packing
      was defined as the ratio between the volume of coils inserted and the volume of
      aneurysm. At follow-up, angiographic results were dichotomized into presence or
      absence of recurrence. The relationship between aneurysm volume to fill, packing,
      and angiographic recurrence was determined by multivariable logistic regression.
      RESULTS: Follow-up angiography (mean follow-up 8.8 months) revealed recurrence in
      14.5% of the aneurysms studied in our series. Recurrent aneurysms had a mean
      packing of 15.1% while stable aneurysms (non-recurrent) had a mean packing of
      23.7%. Multivariable logistic regression analysis showed that aneurysm volume and
      packing were significantly associated with angiographic recurrence. Large volume
      aneurysms (>600 mm(3)) were found to have a higher incidence of recurrence than
      those with small volumes (OR=30.49, p<0.001). Compared with those with high
      packing (>=20%), the less packed aneurysms (<20%) had a higher incidence of
      recurrence (OR=29.01, p=0.002). There was no significant difference between
      aneurysm location, clinical presentation, stent assistance, duration of follow
      up, and recurrence. CONCLUSIONS: Coiling large volume (>600 mm(3)) intracranial
      aneurysms are more likely to have a recurrence than small ones. High packing
      (>=20%) provides better protection against recurrence of the aneurysm.

PMID- 24107599
TI  - Quantitative LC-MS/MS analysis of seven ginsenosides and three aconitum alkaloids
      in Shen-Fu decoction.
AB  - BACKGROUND: Shen-Fu decoction is a traditional Chinese medicine prescription with
      a 3:2 ratio of Radix Ginseng and Fuzi (Radix Aconiti lateralis praeparata).
      Ginsenosides and alkaloids are considered to be the main active components of
      Shen-Fu decoction. However, no analytical methods have been used to
      quantitatively analyse both components in Shen-Fu decoction simultaneously.
      RESULTS: We successfully developed a rapid resolution liquid chromatography
      coupled with tandem mass spectrometry (RRLC-MS/MS) method for the simultaneous
      analysis of seven ginsenosides and three aconitum alkaloids in Shen-Fu decoction,
      the decoction of Radix ginseng and Fuzi (Radix Aconiti lateralis praeparata).
      Chromatogrpahic separation by RPLC was achieved using a reversed-phase column and
      a water/acetonitrile mobile phase, containing 0.05% formic acid and using a
      gradient system. The method was optimized to allow for simultaneous analysis of
      all analytes in 11minutes without the need for baseline resolution of the
      components. Furthermore, the separation demonstrated good linearity (r > 0.9882),
      repeatability (RSD < 7.01%), intra- and inter-day precisions (RSD < 5.06%) and
      high yields of recovery (91.13-111.97%) for ten major constituents, namely
      ginsenoside-Re, Rg1, Rb1, Rc, Rb2, Rd, Rf, aconitine, hypacoitine and
      mesaconitine. CONCLUSIONS: The developed method could be used as a rapid and
      reliable approach for assessment of the quantity of the major constituents in
      Shen-Fu decoction.

PMID- 24107600
TI  - First-principles local stress in crystalline and amorphous metals.
AB  - Atomic size is perhaps the most commonly used concept to describe material
      properties. Advances in the understanding of materials are hindered by the
      available choices of simplifying concepts that can be used. However, the precise
      definition of atomic size is not easy, and often controversial. Atomic level
      stress provides a new interpretive tool that draws on the rich formalism of solid
      mechanics for use with density functional calculations to advance a deeper
      understanding of the properties of materials. We discuss atomic level stresses in
      liquids and glasses and make comparisons with ordered and disordered crystals.
      Somewhat surprisingly, even ordered compounds that are under no macroscopic
      stress and whose individual atoms are completely relaxed, i.e., no force acting
      on them, can have substantial atomic level stresses. On top of concepts such as
      the ionicity or covalency, the atomic level stresses add to the arsenal of
      analysis tools that are available to interpret the results of density functional
      calculations. 

PMID- 24107602
TI  - Despite significant advances in prevention, childhood caries remains a global
      public health challenge. Foreword.

PMID- 24107601
TI  - Imaging and cerebrospinal fluid biomarkers in the search for Alzheimer's disease
      mechanisms.
AB  - BACKGROUND: The pathophysiological process of Alzheimer's disease (AD) begins
      many years before the emergence of clinical symptoms (preclinical AD). A
      hypothetical biomarker progression in the pathogenesis of AD has been suggested,
      beginning with the deposition of amyloid-beta (Abeta) and followed by increases
      in neurofibrillary tangles, synaptic loss, hippocampal atrophy, and lastly,
      cognitive impairment. OBJECTIVE: We explored the effect of several risk factors
      for AD on the pattern of AD biomarker expression in normal subjects. METHODS: AD
      biomarker evidence was examined at baseline in 96 cognitively normal elderly
      subjects with none or at least one of the following: ApoE4+ allele, a maternal
      history of AD (mFHx), sleep-disordered breathing (SDB), and longitudinal evidence
      of decline to mild cognitive impairment or AD (decliners) at follow-up. RESULTS:
      Decliners and ApoE4+ subjects presented with expected reduced cerebrospinal fluid
      Abeta42, elevated P-tau and T-tau. In addition, decliners had fluorodeoxyglucose
      positron emission tomography hypometabolism in the medial temporal lobe.
      Individuals with mFHx demonstrated no Abeta42 effect, but had elevations in P-tau
      and T-tau. SDB was found to be associated with elevated Abeta42, P-tau and T-tau,
      as well as with reduced medial temporal lobe glucose metabolic rates. CONCLUSION:
      Our results indicate a heterogeneous biomarker expression, suggesting diversity
      of AD pathways in at-risk presymptomatic subjects.

PMID- 24107603
TI  - Analysis of health behaviour change interventions for preventing dental caries
      delivered in primary schools.
AB  - To improve oral health in children, the key behaviours (tooth brushing and sugar
      control) responsible for development of dental caries need to be better
      understood, as well as how to promote these behaviours effectively so they become
      habitual; and, the specific, optimal techniques to use in interventions. The aim
      of this paper is to describe and analyse the behaviour change techniques that
      have been used in primary school-based interventions to prevent dental caries
      (utilizing a Cochrane systematic review that we have undertaken) and to identify
      opportunities for improving future interventions by incorporating a comprehensive
      range of behaviour change techniques. Papers of five interventions were reviewed
      and data were independently extracted. Results indicate that behaviour change
      techniques were limited to information-behaviour links, information on
      consequences, instruction and demonstration of behaviours. None of the
      interventions were based on behaviour change theory. We conclude that behaviour
      change techniques used in school interventions to reduce dental caries were
      limited and focused around providing information about how behaviour impacts on
      health and the consequences of not developing the correct health behaviours as
      well as providing oral hygiene instruction. Establishing which techniques are
      effective is difficult due to poor reporting of interventions in studies. Future
      design of oral health promotion interventions using behaviour change theory for
      development and evaluation (and reporting results in academic journals) could
      strengthen the potential for efficacy and provide a framework to use a much wider
      range of behaviour change techniques. Future studies should include development
      and publication of intervention manuals which is becoming standard practice in
      other health promoting programmes.

PMID- 24107604
TI  - An overview of children's oral health-related quality of life assessment: from
      scale development to measuring outcomes.
AB  - The objectives of this paper are to present an overview of children's oral health
      related quality of life and include specific applications for using quality of
      life assessment in dental research. The process of developing pediatric oral
      health- related quality of life measures, in particular the Child Oral Health
      Impact Profile, is outlined. Examples of children's oral health-related quality
      of life measurement in caries research are also provided. Quality of life
      outcomes are presented and discussed in the context of caries research. Lastly,
      the relevance of measuring clinically meaningful difference in the context of
      measuring outcomes research is highlighted with recommendations for future
      research.

PMID- 24107605
TI  - Family relationships as an explanatory variable in childhood dental caries: a
      systematic review of measures.
AB  - It is widely acknowledged that parental beliefs (self-efficacy) about oral health
      and parental oral health-related behaviours play a fundamental role in the
      establishment of preventative behaviours that will mitigate against the
      development of childhood dental caries. However, little attention has been given
      to the wider perspective of family functioning and family relationships on child
      oral health. For oral health researchers, exploration of this association
      requires the use of reliable, valid and appropriate assessment tools to measure
      family relationships. In order to promote methodologically sound research in oral
      health, this systematic review aims to provide a guide on self-report
      psychometric measures of family functioning that may be suitable to utilize when
      exploring childhood dental caries. This systematic review has identified 29 self
      report measures of family functioning and evaluated them in terms of their
      psychometric support, constructs measured and potential utility for oral health
      research. The majority of the measures reported adequate levels of reliability
      and construct validity. Construct evaluation of the measures identified five core
      domains of family functioning, namely 'communication', 'cohesion/engagement',
      'control', 'involvement' and 'authoritative/rigid parenting style'. The
      constructs were subsequently evaluated with respect to their potential relevance
      to child oral health. Herewith this review provides a framework to guide future
      research to explore family functioning in furthering our understanding of the
      development of childhood dental caries.

PMID- 24107606
TI  - Application of audio computer-assisted self-interviews to collect self-reported
      health data: an overview.
AB  - For assessment of sensitive health behaviors (e.g., sexual behavior, violent
      behaviors, substance use), research is typically limited to an examination of
      self-reports of past behavior. Audio computer-assisted self-interviews (ACASI)
      may enhance the validity of self-report data in research and clinical settings by
      reducing measurement bias. This paper provides an introduction to ACASI for
      collection of self-reported health data. The potential benefits and cost
      effectiveness of ACASI use in research and clinical settings are reviewed. We
      then review the theoretical underpinnings that may underlie differential
      reporting of health behaviors between assessment modalities. Next, we highlight
      studies that have investigated differences in self-reported health behaviors
      between assessment modalities. Lastly, we summarize potential applications of
      ACASI assessments within clinical settings.

PMID- 24107607
TI  - Vegetable variety: an effective strategy to increase vegetable choice in
      children.
AB  - OBJECTIVE: Most children do not meet the recommended intake of vegetables.
      Variety was identified as a potential factor to increase children's intake of
      these foods, as it was shown that variety was effective in improving meal
      composition in adults. Because younger children are suggested to be more
      responsive to internal satiation signals than to external food-related cues
      compared with adults, it is not clear whether variety is effective to improve
      meal composition in 7- to 10-year-old children. DESIGN: Experiment. SETTING:
      Children were assigned one of three different fake food buffets containing pasta,
      chicken, and either one vegetable (carrots or beans) or two vegetables (carrots
      and beans). The children were asked to serve themselves a meal that they would
      like to eat for lunch from the given selection. SUBJECTS: One hundred children
      (fifty-two boys; mean age 8.8 (sd 1.1) years). RESULTS: Children given the two
      vegetable choice served themselves significantly more energy from vegetables
      (mean 64 (sd 51) kJ, 10.9 (sd 9.4) %) compared with children who were offered
      only either carrots (mean 37 (sd 25) kJ, 5.9 (sd 6.5) %) or beans (mean 38 (sd
      34) kJ, 5.6 (sd 6.3) %). The total energy of the meal was not increased,
      indicating that children chose a more balanced lunch when offered more
      vegetables. CONCLUSIONS: School-aged children are responsive to food-related cues
      and variety is effective in increasing their vegetable choice. Serving an
      assortment of vegetables in school cafeterias might be a simple and effective
      strategy to improve children's nutrition.

PMID- 24107608
TI  - Non-lymphoma hematological malignancies in systemic lupus erythematosus.
AB  - OBJECTIVE: To describe non-lymphoma hematological malignancies in systemic lupus
      erythematosus (SLE). METHODS: A large SLE cohort was linked to cancer registries.
      We examined the types of non-lymphoma hematological cancers. RESULTS: In 16,409
      patients, 115 hematological cancers [including myelodysplastic syndrome (MDS)]
      occurred. Among these, 33 were non-lymphoma. Of the 33 non-lymphoma cases, 13
      were of lymphoid lineage: multiple myeloma (n = 5), plasmacytoma (n = 3), B cell
      chronic lymphocytic leukemia (B-CLL; n = 3), precursor cell lymphoblastic
      leukemia (n = 1) and unspecified lymphoid leukemia (n = 1). The remaining 20
      cases were of myeloid lineage: MDS (n = 7), acute myeloid leukemia (AML; n = 7),
      chronic myeloid leukemia (CML; n = 2) and 4 unspecified leukemias. Most of these
      malignancies occurred in female Caucasians, except for plasma cell neoplasms (4/5
      multiple myeloma and 1/3 plasmacytoma cases occurred in blacks). CONCLUSIONS: In
      this large SLE cohort, the most common non-lymphoma hematological malignancies
      were myeloid types (MDS and AML). This is in contrast to the general population,
      where lymphoid types are 1.7 times more common than myeloid non-lymphoma
      hematological malignancies. Most (80%) multiple myeloma cases occurred in blacks;
      this requires further investigation.

PMID- 24107609
TI  - Predictive factors for different subgroups of central lymph node metastasis in
      unilateral papillary thyroid carcinoma.
AB  - AIMS: We aimed to investigate the incidence rates and risk factors for different
      subgroups of central neck lymph node (LN) metastasis (prelaryngeal, ipsilateral
      paratracheal, pretracheal, and contralateral paratracheal) in unilateral
      papillary thyroid carcinoma (PTC) patients with clinically negative neck nodes
      (cN0). METHODS: We evaluated 184 patients from 2007 to 2009. The relationships
      between different subgroups of LN metastasis and clinical pathological factors
      were analyzed. RESULTS: The incidence rates of different central LN metastases
      were diverse. Multivariate analysis indicated that lymphovascular invasion,
      perithyroidal invasion, and tumor size were risk factors for ipsilateral
      paratracheal central LN metastasis; tumor size was an independent risk factor for
      pretracheal central LN metastasis, and pretracheal or/and ipsilateral
      paratracheal central LN metastasis were risk factors for contralateral
      paratracheal central LN metastasis. CONCLUSION: The extent of elective central LN
      dissection (CLND) should be decided based on different clinical pathological
      factors in cN0 PTC patients. Moreover, elective prelaryngeal CLND may be
      unnecessary.

PMID- 24107610
TI  - TaOx-based resistive switching memories: prospective and challenges.
AB  - Resistive switching memories (RRAMs) are attractive for replacement of
      conventional flash in the future. Although different switching materials have
      been reported; however, low-current operated devices (<100 MUA) are necessary for
      productive RRAM applications. Therefore, TaOx is one of the prospective switching
      materials because of two stable phases of TaO2 and Ta2O5, which can also control
      the stable low- and high-resistance states. Long program/erase endurance and data
      retention at high temperature under low-current operation are also reported in
      published literature. So far, bilayered TaOx with inert electrodes (Pt and/or Ir)
      or single layer TaOx with semi-reactive electrodes (W and Ti/W or Ta/Pt) is
      proposed for real RRAM applications. It is found that the memory characteristics
      at current compliance (CC) of 80 MUA is acceptable for real application; however,
      data are becoming worst at CC of 10 MUA. Therefore, it is very challenging to
      reduce the operation current (few microampere) of the RRAM devices. This study
      investigates the switching mode, mechanism, and performance of low-current
      operated TaOx-based devices as compared to other RRAM devices. This topical
      review will not only help for application of TaOx-based nanoscale RRAM devices
      but also encourage researcher to overcome the challenges in the future
      production. 

PMID- 24107611
TI  - Molecular background of urate transporter genes in patients with exercise-induced
      acute kidney injury.
AB  - BACKGROUND/AIMS: Exercise-induced acute renal failure [exercise-induced acute
      kidney injury (EI-AKI)] is defined as AKI due to heavy anaerobic exercise.
      Although hypouricemia is known to be a risk factor for the onset of EI-AKI, a
      direct causal link between EI-AKI and serum uric acid has not been established.
      This study aimed to analyze urate transporter genes in patients with EI-AKI and
      its molecular mechanism. METHODS: Genomic DNA and total RNA were isolated from
      peripheral blood leukocytes of patients with a history of EI-AKI. Mutations were
      analyzed by PCR and a direct sequencing method. We first analyzed the SLC22A12
      gene, and then the SLC2A9 gene if no mutations were found in SLC22A12. RESULTS:
      Seventeen patients were enrolled in this study and 16 had mutations: 15 in
      SLC22A12 and 1 in SLC2A9. Fourteen (82.4%) patients showed hypouricemia, and all
      of the patients with hypouricemia had either homozygous or compound heterozygous
      mutations in SLC22A12 or SLC2A9, which confirmed that all of them had renal
      hypouricemia. Two patients had heterozygous mutations of SLC22A12, and they were
      not accompanied by hypouricemia. One patient was found to have no mutations in
      SLC22A12 or SLC2A9. CONCLUSION: We were able to determine the genetic background
      of urate transporter genes in patients with EI-AKI. Decreased function of urate
      transporters, rather than decreased serum uric acid levels, may be of great
      importance for the onset of EI-AKI.

PMID- 24107612
TI  - Is the low-grade squamous intraepithelial lesion/atypical squamous cells cannot
      exclude high-grade squamous intraepithelial lesion category associated with
      cervical intraepithelial neoplasia 2?
AB  - OBJECTIVE: A number of cervical smears may exhibit unequivocal low-grade squamous
      intraepithelial lesions (LSIL) in association with atypical cells
      cytomorphologically suspicious, but not sufficient to be interpreted as high
      grade squamous intraepithelial lesions (HSIL). These lesions are presently called
      LSIL, atypical squamous cells cannot exclude HSIL (LSIL/ASC-H). Previous studies
      have shown that LSIL/ASC-H and ASC-H are both equivocal for HSIL and have a high
      risk of underlying HSIL. However, in researching the literature only two studies
      were found which rendered the results as cervical intraepithelial neoplasia (CIN)
      2 and CIN3 separately. The purpose of this study was to compare the distribution
      of biopsy results for CIN2 and CIN3 in patients with ASC-H, HSIL, and LSIL/ASC-H.
      STUDY DESIGN: Between January 2005 and December 2011, cervicovaginal smears
      (98,594) with a diagnosis of ASC-H, LSIL, LSIL/ASC-H, or HSIL were re-evaluated
      to determine the prevalence of future lesion development. RESULTS: A total of 252
      patients who had histologic follow-up within a year were selected. Among these,
      LSIL/ASC-H (31.7%) had the highest prevalence of CIN2 between LSIL (9.3%), ASC-H
      (10%), and HSIL (16%). All differences were statistically significant.
      CONCLUSION: Because of the high predictive value of CIN2, LSIL/ASC-H may have
      further importance, especially in women of different age groups.

PMID- 24107613
TI  - Ureidoglycolate hydrolase, amidohydrolase, lyase: how errors in biological
      databases are incorporated in scientific papers and vice versa.
AB  - An opaque biochemical definition, an insufficient functional characterization, an
      interpolated database description, and a beautiful 3D structure with a wrong
      reaction. All these are elements of an exemplar case of misannotation in
      biological databases and confusion in the scientific literature concerning genes
      and enzymes acting on ureidoglycolate, an intermediate of purine catabolism. Here
      we show biochemical evidence for the relocation of genes assigned to EC 3.5.3.19
      (ureidoglycolate hydrolase, releasing ammonia), such as allA of Escherichia coli
      or DAL3 of Saccharomyces cerevisiae, to EC 4.3.2.3 (ureidoglycolate lyase,
      releasing urea). The EC 3.5.3.19 should be more appropriately named
      ureidoglycolate amidohydrolase and include genes equivalent to UAH of Arabidopsis
      thaliana. The distinction between ammonia- or urea-releasing activities from
      ureidoglycolate is relevant for the understanding of nitrogen metabolism in
      various organisms and of virulence factors in certain pathogens rather than a
      nomenclature problem. We trace the original fault in database annotation and
      provide a rationale for its incorporation and persistence in the scientific
      literature. Notwithstanding the technological distance, yet not surprising for
      the constancy of human nature, error categories and mechanisms established in the
      study of the work of amanuensis monks still apply to the modern curation of
      biological databases. 

PMID- 24107614
TI  - Free fatty acids inhibit protein tyrosine phosphatase 1B and activate Akt.
AB  - BACKGROUND/AIMS: Accumulating evidence has suggested that free fatty acids (FFAs)
      interact with protein kinases and protein phosphatases. The present study
      examined the effect of FFAs on protein phosphatases and Akt. METHODS: Activities
      of protein phosphatase 1 (PP1), protein phosphatase 2A (PP2A), and protein
      tyrosine phosphatase 1B (PTP1B) were assayed under the cell-free conditions.
      Phosphorylation of Akt was monitored in MSTO-211H human malignant pleural
      mesothelioma cells without and with knocking-down phosphatidylinositol 3 kinase
      (PI3K) or 3-phosphoinositide-dependent protein kinase-1 (PDK1). RESULTS: In the
      cell-free assay, unsaturated FFAs (uFFAs) such as oleic, linoleic and linolenic
      acid and saturated FFAs (sFFAs) such as stearic, palmitic, myristic, and behenic
      acid markedly reduced PTP1B activity, with the potential for uFFAs greater than
      that for sFFAs. All the investigated sFFAs inhibited PP2A activity, but otherwise
      no inhibition was obtained with uFFAs. Both uFFAs and sFFAs had no effect on PP1
      activity. Oleic acid phosphorylated Akt both on Thr308 and Ser473, while stearic
      acid phosphorylated Akt on Thr308 alone. The effects of oleic and stearic acid on
      Akt phosphorylation were abrogated by the PI3K inhibitor wortmannin or the PDK1
      inhibitor BX912 and also by knocking-down PI3K or PDK1. CONCLUSION: The results
      of the present study indicate that uFFAs and sFFAs could activate Akt through a
      pathway along a PI3K/PDK1/Akt axis in association with PTP1B inhibition.

PMID- 24107616
TI  - Incidence of adult-onset asthma after hypothetical interventions on body mass
      index and physical activity: an application of the parametric g-formula.
AB  - High body mass index (BMI) (calculated as weight (kg)/height (m)(2)) is
      associated with increased asthma risk, but uncertainty persists about the role of
      physical activity. We estimated the independent and joint associations of
      hypothetical interventions on BMI and physical activity with the risk of adult
      onset asthma in 76,470 asthma-free women from the Nurses' Health Study who were
      followed between 1988 and 1998. Information about asthma, BMI, physical activity,
      and other factors was updated every 2 years. We used the parametric g-formula to
      estimate the 10-year asthma risk in the following 4 scenarios: no intervention,
      5% BMI reduction in a 2-year period for those who were overweight or obese, at
      least 2.5 hours/week of moderate-to-vigorous physical activity, and both of the
      previous 2 interventions. At baseline, women had a mean age of 55 (standard
      deviation, 7) years and a mean BMI of 25.4 (standard deviation, 4.8). Median time
      spent in physical activity was 0.7 hours/week. During follow-up, 1,146 women
      developed asthma. The 10-year asthma risk under no intervention was 1.5%.
      Compared with no intervention, the population risk ratios were 0.96 (95%
      confidence interval (CI): 0.93, 0.99) under the BMI intervention, 0.96 (95% CI:
      0.81, 1.10) under the physical activity intervention, and 0.92 (95% CI: 0.78,
      1.06) under the joint intervention. Interventions on BMI and physical activity
      may have a modest impact on the risk of adult-onset asthma in this population of
      US women.

PMID- 24107617
TI  - Distinct roles of endogenous vascular endothelial factor receptor 1 and 2 in
      neural protection after spinal cord injury.
AB  - Secondary degeneration after spinal cord injury (SCI) is caused by increased
      vascular permeability, infiltration of inflammatory cells, and subsequent focal
      edema. Therapeutic interventions using neurotrophic factors have focused on the
      prevention of such reactions to reduce cell death and promote tissue
      regeneration. Vascular endothelial growth factor (VEGF) is a potent angiogenic
      and vascular permeability factor. However, the effect of VEGF on SCI remains
      controversial. VEGF signaling is primarily regulated through two primary
      receptors, VEGF receptor 1 (VEGF-R1) and VEGF receptor 2 (VEGF-R2). The purpose
      of this study was to examine the effects of intraperitoneal administration of
      VEGF-R1- and VEGF-R2-neutralizing antibodies on a mouse model of SCI. VEGF-R1
      blockade, but not VEGF-R2 blockade, decreased the permeability and infiltration
      of inflammatory cells, and VEGF-R2 blockade caused a significant increase in
      neuronal apoptosis in the acute phase of SCI. VEGF-R2 blockade decreased the
      residual tissue area and the number of neural fibers in the chronic phase of SCI.
      VEGF-R2 blockade worsened the functional recovery and prolonged the latency of
      motor evoked potentials. These data suggest that endogenous VEGF-R2 plays a
      crucial role in neuronal protection after SCI. 

PMID- 24107615
TI  - Obesity and mortality after breast cancer by race/ethnicity: The California
      Breast Cancer Survivorship Consortium.
AB  - We investigated body size and survival by race/ethnicity in 11,351 breast cancer
      patients diagnosed from 1993 to 2007 with follow-up through 2009 by using data
      from questionnaires and the California Cancer Registry. We calculated hazard
      ratios and 95% confidence intervals from multivariable Cox proportional hazard
      model-estimated associations of body size (body mass index (BMI) (weight
      (kg)/height (m)(2)) and waist-hip ratio (WHR)) with breast cancer-specific and
      all-cause mortality. Among 2,744 ascertained deaths, 1,445 were related to breast
      cancer. Being underweight (BMI <18.5) was associated with increased risk of
      breast cancer mortality compared with being normal weight in non-Latina whites
      (hazard ratio (HR) = 1.91, 95% confidence interval (CI): 1.14, 3.20), whereas
      morbid obesity (BMI >= 40) was suggestive of increased risk (HR = 1.43, 95% CI:
      0.84, 2.43). In Latinas, only the morbidly obese were at high risk of death (HR =
      2.26, 95% CI: 1.23, 4.15). No BMI-mortality associations were apparent in African
      Americans and Asian Americans. High WHR (quartile 4 vs. quartile 1) was
      associated with breast cancer mortality in Asian Americans (HR = 2.21, 95% CI:
      1.21, 4.03; P for trend = 0.01), whereas no associations were found in African
      Americans, Latinas, or non-Latina whites. For all-cause mortality, even stronger
      BMI and WHR associations were observed. The impact of obesity and body fat
      distribution on breast cancer patients' risk of death may vary across
      racial/ethnic groups.

PMID- 24107620
TI  - X-ray scattering studies of structural phase transitions in pyrochlore Cd2Nb2O7.
AB  - Structural phase transitions in pyrochlore Cd2Nb2O7 were studied by means of
      single crystal x-ray scattering. On cooling below the ferroelastic transition at
      T1 = 204 K, the cubic Bragg peaks broaden in a manner consistent with weak
      orthorhombic distortion. The distortion evolves rather smoothly through the
      ferroelectric transition at T2 = 196 K, which explains the absence of sharp
      anomalies in the heat capacity and dielectric constant at this transition. At
      lower temperatures, the anomalous relaxor-like character of this compound is
      evident as a gradual reduction in the Bragg peak intensities, which continues
      down to the onset of another transition at T3 = 85 K. The studies of two Bragg
      peaks that are forbidden within the cubic phase reveal an interesting disparity:
      while the intensity for one of them increases in a classical mean-field manner
      below T1, the other shows unconventional behavior that is reminiscent of the
      pyrochlore superconductor Cd2Re2O7.

PMID- 24107618
TI  - Automatic segmentation of right ventricular ultrasound images using sparse matrix
      transform and a level set.
AB  - An automatic segmentation framework is proposed to segment the right ventricle
      (RV) in echocardiographic images. The method can automatically segment both
      epicardial and endocardial boundaries from a continuous echocardiography series
      by combining sparse matrix transform, a training model, and a localized region
      based level set. First, the sparse matrix transform extracts main motion regions
      of the myocardium as eigen-images by analyzing the statistical information of the
      images. Second, an RV training model is registered to the eigen-images in order
      to locate the position of the RV. Third, the training model is adjusted and then
      serves as an optimized initialization for the segmentation of each image.
      Finally, based on the initializations, a localized, region-based level set
      algorithm is applied to segment both epicardial and endocardial boundaries in
      each echocardiograph. Three evaluation methods were used to validate the
      performance of the segmentation framework. The Dice coefficient measures the
      overall agreement between the manual and automatic segmentation. The absolute
      distance and the Hausdorff distance between the boundaries from manual and
      automatic segmentation were used to measure the accuracy of the segmentation.
      Ultrasound images of human subjects were used for validation. For the epicardial
      and endocardial boundaries, the Dice coefficients were 90.8 +/- 1.7% and 87.3 +/-
      1.9%, the absolute distances were 2.0 +/- 0.42 mm and 1.79 +/- 0.45 mm, and the
      Hausdorff distances were 6.86 +/- 1.71 mm and 7.02 +/- 1.17 mm, respectively. The
      automatic segmentation method based on a sparse matrix transform and level set
      can provide a useful tool for quantitative cardiac imaging. 

PMID- 24107621
TI  - Neuroinflammation and beta amyloid deposition in Alzheimer's disease: in vivo
      quantification with molecular imaging.
AB  - BACKGROUND/AIMS: Neuroinflammation plays a crucial role in the pathogenesis of
      Alzheimer's disease (AD). Its relationship with underlying beta amyloid
      deposition remains unclear. In vivo visualization of microglial activation has
      become possible with the development of molecular imaging ligands when used with
      positron emission tomography (PET). The translocator protein (TSPO) is
      upregulated during neuroinflammation. Consequently, targeting TSPO with
      radiolabeled ligands for PET is an attractive biomarker for neuroinflammation.
      METHODS: A review of the research literature on PET imaging which studied in vivo
      neuroinflammation in AD subjects and its relationship with amyloid load was
      performed, including papers published between 2001 and 2012. RESULTS: Six studies
      were included using either [(11)C]PK-11195 or another non-TSPO radioligand that
      binds to the monoaminooxidase B. All the studies evaluated amyloid load with
      [(11)C]PIB. Microglial activation and astrocytosis are potentially early
      phenomena in AD. However, the individual levels of amyloid deposition and
      microglial activation were not correlated. CONCLUSION: Noninvasive in vivo
      molecular imaging to visualize neuroinflammation in AD may contribute to our
      understanding of the kinetics of neuroinflammation and its relationship to the
      hallmarks of the disease. Both are important for the development of future
      therapeutic modalities and for quantifying the efficacy of future disease
      modifying treatments.

PMID- 24107622
TI  - IL-17 signaling and A20: a balancing act.

PMID- 24107623
TI  - Proteolytic autodigestion: common tissue pathology in Shwachman-Diamond syndrome?

PMID- 24107624
TI  - Centromeres in nuclear architecture.

PMID- 24107625
TI  - BH3-only proteins, Bmf and Bim, in autophagy.

PMID- 24107626
TI  - Epigenomics: one molecule at a time.

PMID- 24107627
TI  - Reprogramming of non-genomic estrogen signaling by the stemness factor SOX2
      enhances the tumor-initiating capacity of breast cancer cells.
AB  - The restoration of pluripotency circuits by the reactivation of endogenous
      stemness factors, such as SOX2, may provide a new paradigm in cancer development.
      The tumoral stem cell reprogramming hypothesis, i.e., the ability of stemness
      factors to redirect normal and differentiated tumor cells toward a less
      differentiated and stem-like state, adds new layers of complexity to cancer
      biology, because the effects of such reprogramming may remain dormant until
      engaged later in response to (epi)genetic and/or (micro)environmental events. To
      test this hypothesis, we utilized an in vitro model of a SOX2-overexpressing
      cancer stem cell (CSC)-like cellular state that was recently developed in our
      laboratory by employing Yamanaka's nuclear reprogramming technology in the
      estrogen receptor alpha (ERalpha)-positive MCF-7 breast cancer cell line. Despite
      the acquisition of distinct molecular features that were compatible with a breast
      CSC-like cellular state, such as strong aldehyde dehydrogenase activity, as
      detected by ALDEFLUOR, and overexpression of the SSEA-4 and CD44 breast CSC
      markers, the tumor growth-initiating ability of SOX2-overexpressing CSC-like MCF
      7 cells solely occurred in female nude mice supplemented with estradiol when
      compared with MCF-7 parental cells. Ser118 phosphorylation of estrogen receptor
      alpha (ERalpha), which is a pivotal integrator of the genomic and nongenomic E
      2/ERalpha signaling pathways, drastically accumulated in nuclear speckles in the
      interphase nuclei of SOX2-driven CSC-like cell populations. Moreover, SOX2
      positive CSC-like cells accumulated significantly higher numbers of actively
      dividing cells, and the highest levels of phospho-Ser118-ERalpha occurred when
      chromosomes lined up on a metaphase plate. The previously unrecognized link
      between E 2/ERalpha signaling and SOX2-driven stem cell circuitry may
      significantly impact our current understanding of breast cancer initiation and
      progression, i.e., SOX2 can promote non-genomic E 2 signaling that leads to
      nuclear phospho-Ser118-ERalpha, which ultimately exacerbates genomic ER signaling
      in response to E 2. Because E 2 stimulation has been recently shown to enhance
      breast tumor-initiating cell survival by downregulating miR-140, which targets
      SOX2, the establishment of a bidirectional cross-talk interaction between the
      stem cell self-renewal regulator, SOX2, and the local and systemic ability of E 2
      to increase breast CSC activity may have profound implications for the
      development of new CSC-directed strategies for breast cancer prevention and
      therapy. 

PMID- 24107628
TI  - Cyclin D1 is a major target of miR-206 in cell differentiation and
      transformation.
AB  - miR-206, a member of the so-called myomiR family, is largely acknowledged as a
      specific, positive regulator of skeletal muscle differentiation. A growing body
      of evidence also suggests a tumor suppressor function for miR-206, as it is
      frequently downregulated in various types of cancers. In this study, we show that
      miR-206 directly targets cyclin D1 and contributes to the regulation of CCND1
      gene expression in both myogenic and non-muscle, transformed cells. We
      demonstrate that miR-206, either exogenous or endogenous, reduces cyclin D1
      levels and proliferation rate in C2C12 cells without promoting differentiation,
      and that miR-206 knockdown in terminally differentiated C2C12 cells leads to
      cyclin D1 accumulation in myotubes, indicating that miR-206 might be involved in
      the maintenance of the post-mitotic state. Targeting of cyclin D1 might also
      account, at least in part, for the tumor-suppressor activity suggested for miR
      206 in previous studies. Accordingly, the analysis of neoplastic and matched
      normal lung tissues reveals that miR-206 downregulation in lung tumors
      correlates, in most cases, with higher cyclin D1 levels. Moreover, gain-of
      function experiments with cancer-derived cell lines and with in vitro transformed
      cells indicate that miR-206-mediated cyclin D1 repression is directly coupled to
      growth inhibition. Altogether, our data highlight a novel activity for miR-206 in
      skeletal muscle differentiation and identify cyclin D1 as a major target that
      further strengthens the tumor suppressor function proposed for miR-206. 

PMID- 24107629
TI  - NEDD4 E3 ligase inhibits the activity of the Hippo pathway by targeting LATS1 for
      degradation.
AB  - Proper regulation of cell proliferation, cell apoptosis, and cell death are vital
      for the development and survival of living organisms. Failure or dysfunction of
      any of these processes can have devastating effects, including cancer. The Hippo
      pathway, first discovered in Drosophila, has been found to be a major growth
      regulatory signaling pathway that controls these crucial processes and has been
      implicated in cell-progress regulation and organ size determination. Abnormal
      regulation of this pathway has been found in several cancer types. However, the
      mechanisms that regulate the pathway and its core members yet have to be
      elucidated. One of the main core components of this pathway is LATS1, a
      serine/threonine kinase. Therefore, understanding how LATS1 activity is regulated
      is expected to shed light on new mechanisms that regulate the Hippo pathway. In
      the current work, we identified several potential LATS1 regulators and proved
      that NEDD4 E3 ubiquitin ligase controls LATS1 stability. We demonstrate that
      NEDD4 directly interacts with LATS1, leading to ubiquitination and decreased
      levels of LATS1 and, thus, increased YAP localization in the nucleus, which
      subsequently increases the transcriptional activity of YAP. As such, we show that
      NEDD4 acts as an additional regulator of the Hippo pathway on the protein level
      via interactions between WW domain-containing and PPxY motif-containing proteins.
      These findings might be applied in the development of new therapeutic approaches
      through the activation of LATS1. 

PMID- 24107630
TI  - Nucleoporin Nup62 maintains centrosome homeostasis.
AB  - Centrosomes are comprised of 2 orthogonally arranged centrioles surrounded by the
      pericentriolar material (PCM), which serves as the main microtubule organizing
      center of the animal cell. More importantly, centrosomes also control spindle
      polarity and orientation during mitosis. Recently, we and other investigators
      discovered that several nucleoporins play critical roles during cell division.
      Here, we show that nucleoporin Nup62 plays a novel role in centrosome integrity.
      Knockdown of Nup62 induced mitotic arrest in G 2/M phases and mitotic cell death.
      Depletion of Nup62 using RNA interference results in defective centrosome
      segregation and centriole maturation during the G 2 phase. Moreover, Nup62
      depletion in human cells leads to the appearance of multinucleated cells and
      induces the formation of multipolar centrosomes, centriole synthesis defects,
      dramatic spindle orientation defects, and centrosome component rearrangements
      that impair cell bi-polarity. Our results also point to a potential role of Nup62
      in targeting gamma-tubulin and SAS-6 to the centrioles. 

PMID- 24107631
TI  - The proteolytic YB-1 fragment interacts with DNA repair machinery and enhances
      survival during DNA damaging stress.
AB  - The Y-box binding protein 1 (YB-1) is a DNA/RNA-binding nucleocytoplasmic
      shuttling protein whose regulatory effect on many DNA and RNA-dependent events is
      determined by its localization in the cell. We have shown previously that YB-1 is
      cleaved by 20S proteasome between E219 and G220, and the truncated N-terminal YB
      1 fragment accumulates in the nuclei of cells treated with DNA damaging drugs. We
      proposed that appearance of truncated YB-1 in the nucleus may predict multiple
      drug resistance. Here, we compared functional activities of the full-length and
      truncated YB-1 proteins and showed that the truncated form was more efficient in
      protecting cells against doxorubicin treatment. Both forms of YB-1 induced
      changes in expression of various genes without affecting those responsible for
      drug resistance. Interestingly, although YB-1 cleavage did not significantly
      affect its DNA binding properties, truncated YB-1 was detected in complexes with
      Mre11 and Rad50 under genotoxic stress conditions. We conclude that both full
      length and truncated YB-1 are capable of protecting cells against DNA damaging
      agents, and the truncated form may have an additional function in DNA repair. 

PMID- 24107632
TI  - SMG-1 suppresses CDK2 and tumor growth by regulating both the p53 and Cdc25A
      signaling pathways.
AB  - The DNA damage response is coordinated by phosphatidylinositol 3-kinase-related
      kinases, ATM, ATR, and DNA-PK. SMG-1 is the least studied stress-responsive
      member of this family. Here, we show that SMG-1 regulates the G 1/S checkpoint
      through both a p53-dependent, and a p53-independent pathway. We identify Cdc25A
      as a new SMG-1 substrate, and show that cells depleted of SMG-1 exhibit prolonged
      Cdc25A stability, failing to inactivate CDK2 in response to radiation. Given an
      increased tumor growth following depletion of SMG-1, our data demonstrate a novel
      role for SMG-1 in regulating Cdc25A and suppressing oncogenic CDK2 driven
      proliferation, confirming SMG-1 as a tumor suppressor. 

PMID- 24107633
TI  - Glucose promotes breast cancer aggression and reduces metformin efficacy.
AB  - Metformin treatment has been associated with a decrease in breast cancer risk and
      improved survival. Metformin induces complex cellular changes, resulting in
      decreased tumor cell proliferation, reduction of stem cells, and apoptosis. Using
      a carcinogen-induced rodent model of mammary tumorigenesis, we recently
      demonstrated that overfeeding in obese animals is associated with a 50% increase
      in tumor glucose uptake, increased proliferation, and tumor cell reprogramming to
      an "aggressive" metabolic state. Metformin significantly inhibited these pro
      tumorigenic effects. We hypothesized that a dynamic relationship exists between
      chronic energy excess (glucose by dose) and metformin efficacy/action. Media
      glucose concentrations above 5 mmol/L was associated with significant increase in
      breast cancer cell proliferation, clonogenicity, motility,
      upregulation/activation of pro-oncogenic signaling, and reduction in apoptosis.
      These effects were most significant in triple-negative breast cancer (TNBC) cell
      lines. High-glucose conditions (10 mmol/L or above) significantly abrogated the
      effects of metformin. Mechanisms of metformin action at normal vs. high glucose
      overlapped but were not identical; for example, metformin reduced IGF-1R
      expression in both the HER2+ SK-BR-3 and TNBC MDA-MB-468 cell lines more
      significantly at 5, as compared with 10 mmol/L glucose. Significant changes in
      gene profiles related to apoptosis, cellular processes, metabolic processes, and
      cell proliferation occurred with metformin treatment in cells grown at 5 mmol/L
      glucose, whereas under high-glucose conditions, metformin did not significantly
      increase apoptotic/cellular death genes. These data indicate that failure to
      maintain glucose homeostasis may promote a more aggressive breast cancer
      phenotype and alter metformin efficacy and mechanisms of action. 

PMID- 24107635
TI  - A sock for foot-drop: a preliminary study on two chronic stroke patients.
AB  - BACKGROUND: Foot-drop is a common motor impairment of chronic stroke patients,
      which may be addressed with an ankle foot orthosis. Although there is reasonable
      evidence of effectiveness for ankle foot orthoses, user compliance is sometimes
      poor. This study investigated a new alternative to the ankle foot orthosis, the
      dorsiflex sock. CASE DESCRIPTION AND METHODS: The dorsiflex sock was evaluated
      using an A-B single case experimental design. Two community-dwelling, chronic
      stroke patients with foot-drop participated in this study. Measures were selected
      to span the International Classification of Function, Disability and Health
      domains and user views on the dorsiflex sock were also collected. FINDINGS AND
      OUTCOMES: The dorsiflex sock was not effective in improving participants' walking
      symmetry, speed or energy expenditure. Participant 1 showed improvement in the
      distance he could walk in 6 min when using the dorsiflex sock, but this was in
      keeping with a general improvement trend over the course of this study. However,
      both participants viewed the dorsiflex sock positively and reported a positive
      effect on their walking. CONCLUSION: Despite positive user perceptions, the study
      found no clear evidence that dorsiflex sock is effective in improving foot-drop.
      CLINICAL RELEVANCE: Although the dorsiflex sock offers an attractive alternative
      to an ankle foot orthosis, the case studies found no clear evidence of its
      efficacy. Clinicians should view this device with caution until further research
      becomes available.

PMID- 24107634
TI  - A small ubiquitin binding domain inhibits ubiquitin-dependent protein recruitment
      to DNA repair foci.
AB  - The rapid ubiquitination of chromatin surrounding DNA double-stranded breaks
      (DSB) drives the formation of large structures called ionizing radiation-induced
      foci (IRIF), comprising many DNA damage response (DDR) proteins. This process is
      regulated by RNF8 and RNF168 ubiquitin ligases and is thought to be necessary for
      DNA repair and activation of signaling pathways involved in regulating cell cycle
      checkpoints. Here we demonstrate that it is possible to interfere with ubiquitin
      dependent recruitment of DDR factors by expressing proteins containing ubiquitin
      binding domains (UBDs) that bind to lysine 63-linked polyubiquitin chains.
      Expression of the E3 ubiquitin ligase RAD18 prevented chromatin spreading of
      53BP1 at DSBs, and this phenomenon was dependent upon the integrity of the RAD18
      UBD. An isolated RAD18 UBD interfered with 53BP1 chromatin spreading, as well as
      other important DDR mediators, including RAP80 and the BRCA1 tumor suppressor
      protein, consistent with the model that the RAD18 UBD is blocking access of
      proteins to ubiquitinated chromatin. Using the RAD18 UBD as a tool to impede
      localization of 53BP1 and BRCA1 to repair foci, we found that DDR signaling, DNA
      DSB repair, and radiosensitivity were unaffected. We did find that activated ATM
      (S1981P) and phosphorylated SMC1 (a specific target of ATM) were not detectable
      in DNA repair foci, in addition to upregulated homologous recombination repair,
      revealing 2 DDR responses that are dependent upon chromatin spreading of certain
      DDR factors at DSBs. These data demonstrate that select UBDs containing targeting
      motifs may be useful probes in determining the biological significance of protein
      ubiquitin interactions. 

PMID- 24107636
TI  - Hyalinizing trabecular tumor masquerading as papillary thyroid carcinoma on fine
      needle aspiration.
AB  - BACKGROUND/AIMS: Hyalinizing trabecular tumors are rare neoplasms of the thyroid
      gland often mistaken for thyroid carcinoma on fine-needle aspiration. We review
      the distinguishing characteristics of hyalinizing trabecular tumors and their
      management. METHODS: We present the case of a patient diagnosed with papillary
      thyroid carcinoma on fine-needle aspiration as well as a review of the
      literature. RESULTS: Intraoperative findings were felt to be inconsistent with
      papillary thyroid carcinoma and only a thyroid lobectomy was performed pending
      the results from pathologic evaluation, which confirmed a benign process and a
      diagnosis of hyalinizing trabecular tumor. Due to the diagnostic difficulty in
      distinguishing hyalinizing trabecular tumors from thyroid carcinomas on fine
      needle aspiration, many patients receive overtreatment for what is primarily a
      benign disease. CONCLUSIONS: Recognition of hyalinizing trabecular tumors as a
      possible benign etiology of a thyroid mass can facilitate appropriate management.

PMID- 24107637
TI  - Antithrombin attenuates vascular leakage via inhibiting neutrophil activation in
      acute lung injury.
AB  - OBJECTIVE: To test the hypothesis that restoration of antithrombin plasma
      concentrations attenuates vascular leakage by inhibiting neutrophil activation
      through syndecan-4 receptor inhibition in an established ovine model of acute
      lung injury. DESIGN: Randomized controlled laboratory experiment. SETTING:
      University animal research facility. SUBJECTS: Eighteen chronically instrumented
      sheep. INTERVENTIONS: Following combined burn and smoke inhalation injury (40% of
      total body surface area, third-degree flame burn; 4 * 12 breaths of cold cotton
      smoke), chronically instrumented sheep were randomly assigned to receive an IV
      infusion of 6 IU/kg/hr recombinant human antithrombin III or normal saline (n = 6
      each) during the 48-hour study period. In addition, six sham animals (not
      injured, continuous infusion of vehicle) were used to obtain reference values for
      histological and immunohistochemical analyses. MEASUREMENTS AND MAIN RESULTS:
      Compared to control animals, recombinant human antithrombin III reduced the
      number of neutrophils per hour in the pulmonary lymph (p < 0.01 at 24 and 48 hr),
      alveolar neutrophil infiltration (p = 0.04), and pulmonary myeloperoxidase
      activity (p = 0.026). Flow cytometric analysis revealed a significant reduction
      of syndecan-4-positive neutrophils (p = 0.002 vs control at 24 hr). Treatment
      with recombinant human antithrombin III resulted in a reduction of pulmonary
      nitrosative stress (p = 0.002), airway obstruction (bronchi: p = 0.001,
      bronchioli: p = 0.013), parenchymal edema (p = 0.044), and lung bloodless wet-to
      dry-weight ratio (p = 0.015). Clinically, recombinant human antithrombin III
      attenuated the increased pulmonary transvascular fluid flux (12-48 hr: p <= 0.001
      vs control each) and the deteriorated pulmonary gas exchange (12-48 hr: p < 0.05
      vs control each) without increasing the risk of bleeding. CONCLUSIONS: The
      present study provides evidence for the interaction between antithrombin and
      neutrophils in vivo, its pathophysiological role in vascular leakage, and the
      therapeutic potential of recombinant human antithrombin III in a large animal
      model of acute lung injury.

PMID- 24107638
TI  - Prediction of survival to discharge following cardiopulmonary resuscitation using
      classification and regression trees.
AB  - OBJECTIVES: To predict the likelihood that an inpatient who experiences
      cardiopulmonary arrest and undergoes cardiopulmonary resuscitation survives to
      discharge with good neurologic function or with mild deficits (Cerebral
      Performance Category score = 1). DESIGN: Classification and Regression Trees were
      used to develop branching algorithms that optimize the ability of a series of
      tests to correctly classify patients into two or more groups. Data from 2007 to
      2008 (n = 38,092) were used to develop candidate Classification and Regression
      Trees models to predict the outcome of inpatient cardiopulmonary resuscitation
      episodes and data from 2009 (n = 14,435) to evaluate the accuracy of the models
      and judge the degree of over fitting. Both supervised and unsupervised approaches
      to model development were used. SETTING: 366 hospitals participating in the Get
      With the Guidelines-Resuscitation registry. SUBJECTS: Adult inpatients
      experiencing an index episode of cardiopulmonary arrest and undergoing
      cardiopulmonary resuscitation in the hospital. MEASUREMENTS AND MAIN RESULTS: The
      five candidate models had between 8 and 21 nodes and an area under the receiver
      operating characteristic curve from 0.718 to 0.766 in the derivation group and
      from 0.683 to 0.746 in the validation group. One of the supervised models had 14
      nodes and classified 27.9% of patients as very unlikely to survive neurologically
      intact or with mild deficits (< 3%); the best unsupervised model had 11 nodes and
      classified 21.7% as very unlikely to survive. CONCLUSIONS: We have developed and
      validated Classification and Regression Tree models that predict survival to
      discharge with good neurologic function or with mild deficits following in
      hospital cardiopulmonary arrest. Models like this can assist physicians and
      patients who are considering do-not-resuscitate orders.

PMID- 24107639
TI  - Geriatric experience following cardiac arrest at six interventional cardiology
      centers in the United States 2006-2011: interplay of age, do-not-resuscitate
      order, and outcomes.
AB  - OBJECTIVES: It is not known if aggressive postresuscitation care, including
      therapeutic hypothermia and percutaneous coronary intervention, benefits cardiac
      arrest survivors more than 75 years old. We compared treatments and outcomes of
      patients at six regional percutaneous coronary intervention centers in the United
      States to determine if aggressive care of elderly patients was warranted. DESIGN:
      Retrospective evaluation of registry data. SETTING: Six interventional cardiology
      centers in the United States. PATIENTS: Six hundred and twenty-five unresponsive
      cardiac arrest survivors aged 18-75 were compared with 129 similar patients aged
      more than 75. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Cardiac arrest
      survivors aged more than 75 had more comorbidities (3.0 +/- 1.6 vs 2.0 +/- 1.6, p
      < 0.001), but were matched to younger patients in initial heart rhythm, witnessed
      arrests, bystander cardiopulmonary resuscitation, and total ischemic time.
      Patients aged more than 75 frequently underwent therapeutic hypothermia (97.7%),
      urgent coronary angiography (44.2%), and urgent percutaneous coronary
      intervention (24%). They had more sustained hyperglycemia (70.5% vs 59%, p =
      0.015), less postcooling fever (25.2% vs 35.2%, p = 0.03), were more likely to
      have do-not-resuscitate orders (65.9% vs 48.2%, p < 0.001), and undergo
      withdrawal of life support (61.2% vs 47.5%, p = 0.005). Good functional outcome
      at 6 months (Cerebral Performance Category 1-2) was seen in 27.9% elderly versus
      40.4% younger patients overall (p = 0.01) and in 44% versus 55% (p = 0.13) of
      patients with an initial shockable rhythm. Of 35 survivors more than 75 years
      old, 33 (94.8%) were classified as Cerebral Performance Category 1 or 2 at (mean)
      6.5-month follow-up. In multivariable logistic regression modeling, age more than
      75 was significantly associated with outcome only when the presence of a do-not
      resuscitate order was excluded from the model. CONCLUSIONS: Elderly patients were
      more likely to have do-not-resuscitate orders and to undergo withdrawal of life
      support. Age was independently associated with outcome only when correction for
      do-not-resuscitate status was excluded, and functional outcomes of elderly
      survivors were similar to younger patients. Exclusion of patients more than 75
      years old from aggressive care is not warranted on the basis of age alone.

PMID- 24107640
TI  - Magnetic ordering and charge dynamics in kappa-(BEDT-TTF)2Cu[N(CN)2]Cl.
AB  - The Mott insulator kappa-(BEDT-TTF)2Cu[N(CN)2]Cl consists of molecular dimers
      arranged on an anisotropic triangular lattice. At low temperatures a pronounced
      dielectric anomaly is observed, and eventually a canted antiferromagnetic ground
      state forms. Optical spectroscopy clearly rules out charge imbalance and the
      existence of quantum electric dipoles with a dipolar-spin coupling. Here we
      suggest a novel form of spin-charge coupling where the prominent in-plane
      dielectric response in kappa-(BEDT-TTF)2Cu[N(CN)2]Cl is explained by short-range
      discommensurations of the antiferromagnetic phase in the temperature range 30 K <
      T < 50 K, and by relaxation of charged domain walls in the ferromagnetic
      structure at lower temperatures.

PMID- 24107641
TI  - Neural ganglioside GD2(+) cells define a subpopulation of mesenchymal stem cells
      in adult murine bone marrow.
AB  - BACKGROUND/AIMS: Due to the lack of specific markers, the isolation of pure
      mesenchymal stem cells (MSCs) from murine bone marrow remains an unsolved
      problem. The present study explored whether the neural ganglioside GD2 could
      serve as a single surface marker to uniquely distinguish murine bone marrow MSCs
      (mBM-MSCs) from other marrow elements. METHODS: Immunocytochemistry and flow
      cytometry, in combination with quantitative RT-PCR, were used to identify the
      expression of GD2 on culture-expanded mBM-MSCs. GD2(+) and GD2(-) fractions from
      mBM-MSCs cultures were sorted by immunosorting. Flow cytometry was performed to
      further analyze the biomarkers of GD2-sorted and unsorted cells. Employing CFU-F
      assay and CCK-8 assay, we examined the clonogenic and proliferative capabilities
      of GD2-sorted and unsorted cells. Using oil red O and von Kossa staining assay,
      we also assessed the multi-lineage potential of GD2-sortedand unsorted cells.
      RESULTS: We found that mBM-MSCs expressed a novel surface marker the neural
      ganglioside GD2. Importantly, mBM-MSCs were the only cells within bone marrow
      that expressed this marker. Further studies demonstrated that a homogenous
      population of MSCs could be obtained from bone marrow cultures in early passages
      by GD2 immunosorting. Compared to parental cells, GD2(+)-sorted cells not only
      possessed much higher clonogenic and proliferative capabilities but also had
      significantly stronger differentiation potential to adipocytes and osteoblasts.
      Furthermore, GD2(+)-sorted cells displayed enhanced expression of ES markers SSEA
      1 and Nanog. CONCLUSION: Our observations provide the first demonstration that
      GD2 may serve as a maker for identification and purification of mBM-MSCs.
      Meanwhile, our study indicates that the cells selected by GD2 are a subpopulation
      of MSCs with features of primitive precursor cells.

PMID- 24107642
TI  - Surgery after preoperative chemotherapy for patients with unresectable advanced
      gastric cancer.
AB  - OBJECTIVE: The study aimed to evaluate the efficacy of surgery after preoperative
      chemotherapy for unresectable advanced gastric cancer. METHOD: Twenty patients
      with disappeared peritoneal dissemination or decreased lymph node metastasis by
      systemic chemotherapy underwent surgery (group S), while 14 with peritoneal
      dissemination or lymph nodes >N2 (group C) received continuous systemic
      chemotherapy. Among group S patients, 15 underwent a curative resection (group
      R0), while the other 5 did not microscopically undergo a curative resection
      (group R1). RESULTS: The median survival time for all patients was 535 days.
      Survival time was significantly dependent on the chemotherapy response (p <
      0.002). The survival period in group S was significantly longer than that in
      group C (median survival time 747 vs. 476 days; p < 0.02). The relapse-free
      survival was 299 days in group S. In particular, the survival period of patients
      who underwent R0 surgery by preoperative chemotherapy was significantly longer
      than that of group R1 patients (median survival time 794 vs. 485 days; p < 0.02).
      Multivariate analysis revealed that R0 surgery was a significant and independent
      prognostic factor. CONCLUSION: Surgery was effective for advanced gastric cancer
      patients when performed as R0 resection following the disappearance of non
      curative factors by preoperative chemotherapy.

PMID- 24107643
TI  - Comorbidities associated with vitiligo: a ten-year retrospective study.
AB  - BACKGROUND: Vitiligo is a common disorder of depigmentation that has been
      associated with other autoimmune diseases. No recent large-scale data exist on
      the rates of comorbidities associated with vitiligo from the United States
      population. OBJECTIVES: To identify the prevalence of comorbidities as well as
      associated laboratory abnormalities in vitiligo patients. METHODS: All medical
      records dating from January 1, 2000 to June 21, 2011 within the Research Patient
      Data Repository were evaluated retrospectively using a novel artificial
      intelligence-based computer program. A total of 3,280 patients carrying the
      diagnosis of vitiligo were identified using ICD-9 code 709.01. We randomly
      selected 300 patients and validated the diagnosis by manually reviewing their
      medical records. These results were used to create a model that was then applied
      to the larger set yielding 2,441 true vitiligo patients. 1,657 (68%) were
      diagnosed by dermatologists and 784 (32%) by non-dermatologists. We identified
      the prevalence of other comorbid autoimmune conditions by searching problem lists
      of vitiligo patients and collected laboratory data from the first available data
      point in the system for each patient. RESULTS: Women were more frequently
      represented (57.6%) than men (42.4%). The majority of vitiligo patients were
      White/Caucasian (56.9%), followed by Hispanic/Latino (19.4%). 565 (23%) had one
      of the following comorbidities: 287 thyroid-related, 186 psoriasis, 72 rheumatoid
      arthritis, 59 alopecia areata, 55 inflammatory bowel disease, 53 systemic lupus
      and 20 type I diabetes mellitus. 41% had elevated anti-nuclear antibody levels.
      Almost half of the patients tested had elevated thyroid peroxidase antibodies.
      Over 50% of the patients tested had low or insufficient levels of 25-OH vitamin
      D. CONCLUSION: We found a high prevalence of comorbidities among individuals with
      vitiligo presenting to teaching hospitals in Boston, Mass. Comorbid autoimmune
      conditions were seen in 23% of vitiligo patients, thyroid disorders and psoriasis
      being the most common. Screening for these conditions, especially thyroid
      disorders, should be considered in vitiligo patients.

PMID- 24107644
TI  - Predictive medicine to improve the care of children. Abstracts of the 9th Joint
      Meeting of Paediatric Endocrinology, ESPE-PES-APEG-APPES-ASPAE-JSPE-SLEP. Milan,
      Italy. September 19-22, 2013.

PMID- 24107645
TI  - Macular tractional retinoschisis in proliferative diabetic retinopathy: clinical
      characteristics and surgical outcome.
AB  - PURPOSE: To evaluate the clinical characteristics and surgical outcome of macular
      tractional retinoschisis (TRS) as compared with tractional retinal detachment
      (TRD) in proliferative diabetic retinopathy (PDR). METHODS: This retrospective,
      longitudinal study collected consecutive cases with optical coherence tomography
      (OCT)-confirmed TRS and TRD between January 2007 and June 2013. All cases had
      surgical treatment. Their preoperative findings and follow-up data were
      subsequently compared. RESULTS: Thirty-two eyes (32 patients) with TRS and 32
      eyes (32 patients) with TRD were included. The TRS group had more clinically
      inactive fibrosis and less extensive fibrovascular proliferation than the TRD
      group. The involved area and height of the schisis varied among cases; associated
      macular abnormalities included inner macular cyst (43.75%), lamellar hole (12.5%)
      and foveal detachment (9.38%); sequential OCT in some cases showed a progression
      of macular changes. Both groups had significant visual improvement after surgery.
      Of the patients with TRS, 40.62% had residual retinoschisis. Preoperative best
      corrected visual acuity (BCVA), postoperative BCVA and improvement in visual
      acuity showed no significant difference between TRS and TRD. CONCLUSIONS: Unique
      features exist for macular TRS in PDR. Visual function may benefit from vitreous
      surgery despite residual macular abnormalities in some cases.

PMID- 24107646
TI  - Activation of the interleukin-4/signal transducer and activator of transcription
      6 signaling pathway and homeodomain-interacting protein kinase 2 production by
      tonsillar mononuclear cells in IgA nephropathy.
AB  - BACKGROUND/AIM: Clinical development and exacerbation of IgA nephropathy (IgAN)
      are frequently preceded by episodes of upper respiratory tract infection such as
      tonsillitis. This study aimed to determine the role of the interleukin-4 (IL
      4)/signal transducer and activator of transcription 6 (STAT6) signaling pathway
      and homeodomain-interacting protein kinase 2 (HIPK2) in aberrant IgA1 O
      glycosylation production, and identify potential therapeutic targets in IgAN.
      METHODS: Expression levels of IL-4, STAT6, core1beta1,3-galactosyltransferase
      (C1GALT1C1), core1beta3GalT-specific molecular chaperone (Cosmc) and HIPK2 in
      tonsil components were examined by immunohistochemical and immunofluorescence
      staining. Lymphocytes isolated from 22 patients with IgAN and 24 patients with
      chronic tonsillitis (CT) as controls were cultured for 72 h with or without IL-4,
      lipopolysaccharide (LPS) and alpha-hemolytic streptococcus (HS) stimulation.
      Expression levels of STAT6, C1GALT1C1, Cosmc, HIPK2-mRNA and protein were
      measured by real-time PCR and Western blot analysis, respectively. The
      concentration of IgA1 and level of O-glycosylation were determined by ELISA and
      Vicia villosa (VV) lectin-binding assay. To determine the contribution of HIPK2
      in IgA secretion and O-glycosylation, cells were subjected to experiments for
      evaluation of HIPK2 silencing by Hipk2-siRNA transfection. RESULTS: The IL
      4/STAT6 signaling pathway was highly activated in all tonsil tissues (including
      the germinal center and tonsillar crypt epithelium) of IgAN patients, but the
      gene or protein expression of beta1,3-Gal transferase (C1GALT1) and COSMC
      decreased significantly in patients with IgAN in comparison with those with CT.
      Hipk2 production in the tonsils derived from IgAN patients was significantly
      higher than that of CT patients. HIPK2-mRNA expression significantly negatively
      correlated with renal function as expressed by the estimated glomerular
      filtration rate, and also significantly positively correlated with daily
      proteinuria. The level of IL-4, STAT6 and HIPK2 were closely related with Lee's
      pathological grading system. The levels of mRNA and protein encoding STAT6 and
      Hipk2 in cells coincubated with IL-4, LPS and HS were significantly higher than
      those in the controls without stimulation; however, in the IgAN group the levels
      of mRNA and protein encoding C1GALT1 and Cosmc were significantly lower compared
      to the controls. IgA1 concentrations of supernatants in IgAN patients were
      remarkably higher under conditions of external stimulation. As expected, the
      optical density value of VV lectin binding to IgA1 increased after external
      stimulation in the IgAN group. By siRNA transfection, our results clearly
      indicate that Hipk2 negatively regulates C1GALT1 and Cosmc expression.
      Importantly, HIPK2-siRNA attenuates the aberrant glycosylation of IgA1 secretion.
      CONCLUSION: We identified and confirmed that activation of the IL-4/STAT6
      signaling pathway has a crucial role in aberrant glycosylation of IgA1 secretion.
      HIPK2, a protein kinase previously unrecognized in kidney disease, may mediate
      the glycosylation of IgA1. We believe that HIPK2 could be a new therapeutic
      target for IgAN, especially as protein kinases are 'drugable' targets.

PMID- 24107647
TI  - An evaluation of data-driven motion estimation in comparison to the usage of
      external-surrogates in cardiac SPECT imaging.
AB  - Motion estimation methods in single photon emission computed tomography (SPECT)
      can be classified into methods which depend on just the emission data (data
      driven), or those that use some other source of information such as an external
      surrogate. The surrogate-based methods estimate the motion exhibited externally
      which may not correlate exactly with the movement of organs inside the body. The
      accuracy of data-driven strategies on the other hand is affected by the type and
      timing of motion occurrence during acquisition, the source distribution, and
      various degrading factors such as attenuation, scatter, and system spatial
      resolution. The goal of this paper is to investigate the performance of two data
      driven motion estimation schemes based on the rigid-body registration of
      projections of motion-transformed source distributions to the acquired projection
      data for cardiac SPECT studies. Comparison is also made of six intensity based
      registration metrics to an external surrogate-based method. In the data-driven
      schemes, a partially reconstructed heart is used as the initial source
      distribution. The partially-reconstructed heart has inaccuracies due to limited
      angle artifacts resulting from using only a part of the SPECT projections
      acquired while the patient maintained the same pose. The performance of different
      cost functions in quantifying consistency with the SPECT projection data in the
      data-driven schemes was compared for clinically realistic patient motion
      occurring as discrete pose changes, one or two times during acquisition. The six
      intensity-based metrics studied were mean-squared difference, mutual information,
      normalized mutual information (NMI), pattern intensity (PI), normalized cross
      correlation and entropy of the difference. Quantitative and qualitative analysis
      of the performance is reported using Monte-Carlo simulations of a realistic heart
      phantom including degradation factors such as attenuation, scatter and system
      spatial resolution. Further the visual appearance of motion-corrected images
      using data-driven motion estimates was compared to that obtained using the
      external motion-tracking system in patient studies. Pattern intensity and
      normalized mutual information cost functions were observed to have the best
      performance in terms of lowest average position error and stability with
      degradation of image quality of the partial reconstruction in simulations. In all
      patients, the visual quality of PI-based estimation was either significantly
      better or comparable to NMI-based estimation. Best visual quality was obtained
      with PI-based estimation in one of the five patient studies, and with external
      surrogate based correction in three out of five patients. In the remaining
      patient study there was little motion and all methods yielded similar visual
      image quality. 

PMID- 24107648
TI  - Ultrasonography for identifying tracheal tube position during cardiopulmonary
      resuscitation.

PMID- 24107649
TI  - Reply to letter: Direct real-time tracheal ultrasonography for confirmation of
      endotracheal tube placement: is it enough?

PMID- 24107650
TI  - Serial position effects in patients with mild cognitive impairment and early and
      moderate Alzheimer's disease compared with healthy comparison subjects.
AB  - BACKGROUND/AIMS: This study aimed to investigate whether the serial position
      effects in memory can differentiate patients with different subtypes of mild
      cognitive impairment (MCI) from healthy controls and patients with different
      stages of Alzheimer's disease (AD). METHODS: The serial position effects was
      tested with the CERAD word list task in 184 persons (39 healthy control subjects,
      15 amnestic MCI single domain subjects, 23 amnestic MCI multiple domain subjects,
      31 nonamnestic MCI subjects, 45 early or mild AD patients, and 31 moderate AD
      patients). RESULTS: With progression of dementia, memory deficits increased and
      the impairment in the primacy effect during the learning trials advanced, whereas
      the recall of recent items was less impaired. The serial position profile of
      nonamnestic MCI patients resembled that of healthy control subjects, whereas
      amnestic MCI patients showed poorer performance in all 3 positions but no
      significant difference as a function of serial word position. CONCLUSION:
      Analyses of the serial position effect may be a useful complement to clinical
      neuropsychological measures for distinguishing amnestic MCI patients from normal
      aging and patients with different stages of dementia.

PMID- 24107651
TI  - Infrared microspectroscopy identifies biomolecular changes associated with
      chronic oxidative stress in mammary epithelium and stroma of breast tissues from
      healthy young women: implications for latent stages of breast carcinogenesis.
AB  - Studies of the decades-long latent stages of breast carcinogenesis have been
      limited to when hyperplastic lesions are already present. Investigations of
      earlier stages of breast cancer (BC) latency have been stymied by the lack of
      fiducial biomarkers needed to identify where in histologically normal tissues
      progression toward a BC might be taking place. Recent evidence suggests that a
      marker of chronic oxidative stress (OxS), protein adducts of 4-hydroxy-2-nonenal
      (4HNE), can meet this need. Specifically: (1) 4HNE immunopositive (4HNE+) mammary
      epithelial (ME) cells were found to be prevalent in normal (reduction
      mammoplasty) tissues of most women (including many teenagers) studied,
      representative of those living in the United States' high risk-posing environment
      and: (2) marked (> 1.5-fold) differences were identified between tissues of
      healthy young women with many vs. few 4HNE+ ME cells in the relative levels of
      transcripts for 42 of the 84 OxS-associated genes represented in SABioscience
      Oxidative-Stress/Oxidative-Defense PCR array. Herein we used synchrotron
      radiation-based Fourier-transform infrared (SR-FTIR) microspectroscopy to
      identify molecular changes associated with 4HNE adducts in basal and luminal ME
      cells in terminal ductal units (TDLU), which are the cells of origin of BC, and
      associated intralobular and interlobular stroma, known contributors to
      carcinogenesis. Multivariate analysis-derived wavenumbers differentiated 4HNE+
      and 4HNE- cells in each of the anatomical compartments. Specifically, principal
      component and linear discriminant analyses of mid-infrared spectra obtained from
      these cells revealed unambiguous, statistically highly significant differences in
      the "biochemical fingerprint" of 4HNE+ vs. 4HNE- luminal and basal ME cells, as
      well as between associated intralobular and interlobular stroma. These findings
      demonstrate further SR-FTIR microspectroscopy's ability to identify molecular
      changes associated with altered physiological and/or pathophysiological states,
      in this case with a state of chronic OxS that provides a pro-carcinogenic
      microenvironment. 

PMID- 24107652
TI  - A qualitative study of community home-based care and antiretroviral adherence in
      Swaziland.
AB  - INTRODUCTION: Antiretroviral therapy (ART) has rendered HIV and AIDS a chronic
      condition for individuals in many parts of the world. Adherence, however, is
      integral to achieving chronicity. Studies have shown both relatively high ART
      adherence rates in sub-Saharan Africa and the importance of community home-based
      care (CHBC) to facilitating this process. In light of diminished HIV and AIDS
      funding globally and increased reliance on CHBC throughout Africa, a better
      understanding of how CHBC may strengthen ART adherence is essential to improving
      patients' quality of life, tending to the needs of care supporters and achieving
      healthier populations. METHODS: This article reports findings from a qualitative
      study of a CHBC organiztion serving an estimated 2500 clients in rural Swaziland.
      Semi-structured questionnaires with 79 HIV-positive clients [people living with
      HIV and AIDS (PLWHA)] yielded data on diverse aspects of being HIV positive,
      including insights on whether and how PLWHA perceived care supporters to
      facilitate ART adherence in a high stigma and structurally impoverished setting.
      RESULTS: Ninety-two percent of participants said their health had improved since
      care supporters came into their lives. A major finding was that an estimated 53%
      of participants said they would have died, a few from suicide had the care
      supporter never intervened. More than one in four participants (27.9%) sought HIV
      testing after a care supporter began visiting them. Nearly a third (31%)
      commenced ART after and largely as a consequence of care supporter intervention.
      Approximately one in four (23%) reported that their care supporter had helped
      them to disclose their HIV-positive status to family members. Twenty-seven
      percent said they had felt discouraged or had been discouraged from taking ART by
      members of their family or community. DISCUSSION: General inductive analysis of
      participant reports suggested two social mechanisms of CHBC impact on ART
      adherence: (i) cultivating client-care supporter "talk" to enhance treatment
      uptake and literacy, reduce felt stigma and challenge social pressures to desist
      from ART and (ii) real-time interactions between clients and care supporters
      whereby the care "relationship" was itself the "intervention," providing lay
      counsel, material and financial assistance, and encouragement when clients
      suffered stigma, side effects and other obstacles to adherence. These social
      dynamics of adherence generally fall outside the purview of conventional clinical
      and public health research. CONCLUSIONS: PLWHA reports of care supporter
      practices that enabled ART adherence demonstrated the pivotal role that CHBC
      plays in many PLWHA lives, especially in hard to reach areas. Relative to clinic
      personnel, care supporters are often intensely engaged in clients' experiences of
      sickness, stigma and poverty, rendering them influential in individuals' decision
      making. This influence must be matched with on-going training and support of care
      supporters, as well as a clear articulation with the formal and informal health
      sectors, to ensure that PLWHA are correctly counselled and care supporters
      themselves supported. Overall, findings showed that PLWHA experiences of CHBC
      should be captured and incorporated into any programme aimed at successfully
      implementing the Joint United Nations Programme on HIV and AIDS (UNAIDS)
      Treatment 2.0 agenda Pillar 4 (increasing HIV testing uptake and care linkages)
      and Pillar 5 (strengthening community mobilization).

PMID- 24107653
TI  - Adipose tissue-derived stem cells treated with estradiol enhance survival of
      autologous fat transplants.
AB  - Autologous fat transplantation (AFT) is a common and important operation in
      plastic surgery for soft tissue defects and adipose tissue-derived stem cells
      (ADSCs) are considered as a promising supplement to decrease absorption and
      subsequent side effects due to the ability of multiple differentiation and
      production of vascular endothelial growth factor (VEGF). The capacities of ADSCs
      can be further enhanced by treatment with 17-beta estradiol (E2). Therefore, we
      hypothesized that E2 may promote the potential of ADSCs for AFT. In this study,
      ADSCs were extracted from three female patients by liposuction. In vitro studies
      showed that E2 supplementation at an optimal concentration of 10(-8) M resulted
      in enhanced proliferation, VEGF production, and adipogenic differentiation of
      human ADSCs, and reduced apoptosis rate in a serum-free environment. In addition,
      a nude mice model of fat transplantation was utilized to demonstrate the efficacy
      of ADSC for survival ratio in vivo. These results using the volume of fat tissues
      after 12 weeks compared original volume, revealed that the addition of E2-treated
      ADSCs induced a significantly higher tissue survival ratio (76.9 +/- 1.9%) when
      compared with the ADSC-free system (55.5 +/- 1.5%). Furthermore, increased
      capillary formation stained with hematoxylin-eosin (H&E) was observed in ADSCs
      systems after treatment with E2. Therefore, this study demonstrated E2 could
      promote the capacities of ADSCs about aspects of adipogenic differentiation,
      growth factor secretion and apoptosis reduction in vitro, vascularization
      improvement in vivo, and then enhanced the survival ratio of AFT. 

PMID- 24107654
TI  - A greater reduction of anterior cruciate ligament elasticity in women compared to
      men as a result of delayed onset muscle soreness.
AB  - Women have a higher risk for anterior cruciate ligament (ACL) injuries compared
      to men. ACL elasticity and muscle flexibility are major risk factors for knee
      injuries. The presence of estrogen receptors in connective tissue allows estrogen
      to change the mechanical properties of muscles and ligaments. Delayed onset
      muscle soreness (DOMS) happened when begin unaccustomed levels of exercise. Thus,
      the purpose of this study was to examine ACL elasticity after exercise meant to
      produce DOMS. As a measure of DOMS, visual analog pain scale and quadriceps
      strength were measured. One hundred forty healthy students (age: 25.2 +/- 2.4
      years, height: 165.9 +/- 8.0 cm, weight: 62.5 +/- 10.5 kg, BMI: 22.6 +/- 3.1)
      participated in this investigation and were divided into two groups: men (n = 70)
      and women (n = 70). Visual analog pain scale, ACL elasticity, and quadriceps
      strength were measured before and after the intervention. Subjects participated
      in the same exercise to induce DOMS. To provoke DOMS, subjects accomplished
      squats for 5 minutes for 3 rounds. Greater ACL elasticity, greater pain on the
      subjective pain scale and less muscle strength were found (p < 0.001) in women
      compared to men before and after exercise. A greater reduction of ACL elasticity
      (p < 0.05) was found as a result of DOMS in women compared to men. Women are
      likely to have the damage to the ACL and recover slower compared to men after
      exercise. Thus, we suggest that women should have more time for musculoskeletal
      recovery after heavy exercise. 

PMID- 24107655
TI  - Prevalence of suicide ideation and attempts among Black Americans in later life.
AB  - This article provides the first national estimates of the prevalence and
      correlates of nonfatal suicidal behavior among older Black Americans. There is a
      lack of national data on suicide ideation and attempts across ethnic
      classifications of Blacks in a nationally representative sample. Data are a
      subsample from the National Survey of American Life (NSAL), a national U.S. adult
      household probability sample of 5,191 Black Americans. The WHO Composite
      International Diagnostic Interview (CIDI) was used to assess older Blacks for
      nonfatal suicidal behavior and 14 DSM-IV disorders. Bivariate and multivariate
      logistic regression analyses were employed to delineate patterns and correlates
      of nonfatal suicidal behavior. The estimated lifetime prevalence of suicidal
      ideation and attempts among older Blacks in the United States was 6.1% and 2.1%,
      respectively. On an average it took 2.5 and 5.7 years respectively to go from
      ideation to attempts or from planning to attempts. Surprisingly, among older
      Black adults, men reported attempting suicide and seriously consider taking their
      own lives more than women. Older Blacks at higher risk for suicide attempts were
      middle aged, had poorer health, were anxious, and had multiple DSM-IV disorders.
      The results also show that approximately 1 in 4 attempters and 2 in 5 ideators
      have never sought treatment for their emotional or psychological problems.
      Preventative care, particularly screening in primary care settings, should
      consider these findings when treating older Black Americans for psychiatric
      related risk. 

PMID- 24107656
TI  - The validation of a social functioning questionnaire in an African postconflict
      context.
AB  - This study evaluated the reliability and criterion validity of the Byumba Social
      Functioning Questionnaire (BSFQ), an instrument to measure social functioning in
      Rwanda. The instrument was locally composed in concordance with a well-described
      method for culture-specific and sex-specific function assessment. Respondents in
      a Northern Province of Rwanda (N = 393) were assessed with the BSFQ and a 19-item
      scale (SF-19) drawn from the Medical Outcomes Study 36-Item Short-Form (SF-36).
      The BSFQ's internal consistency was just acceptable for women but poor for men,
      while the SF-19 had good to excellent internal consisteny. BSFQ total scores
      showed a strong floor effect, while the SF-19 showed more variation in total
      score distribution. The BSFQ did not perform as well as we expected, and appears
      not to be suitable for measuring social functioning in the study context. This
      outcome seems to reflect the conceptualization of social functioning used in
      constructing the BSFQ. Implications for the development of culture-specific
      measures of functional status are discussed. 

PMID- 24107657
TI  - Cytologic findings in experimental in vivo fallopian tube brush specimens.
AB  - OBJECTIVE: The fallopian tube is now recognized as a primary source of precursor
      neoplastic lesions for pelvic serous adenocarcinomas. Cytologic features of
      fallopian tube brushings from low-risk patients have not been well described.
      STUDY DESIGN: We describe the cytomorphology of tubal epithelium from
      prospectively collected experimental in vivo brushings from normal fallopian
      tubes of 7 low-risk patients. Liquid-based cytology slides and cell blocks were
      prepared and reviewed on all specimens. RESULTS: Fifteen brush cytology specimens
      were obtained, ten by laparoscopy, four by hysteroscopy and one following
      hysterectomy and bilateral salpingo-oophorectomy on an ex vivo specimen. Variable
      cytologic features were documented for background, cellularity, cellular
      architecture, cilia, nuclear overlap, mitoses, nuclear pleomorphism, nuclear
      membrane changes and nucleoli. Negative P53 and Ki-67 stain results were
      documented in available cell blocks. Histopathologic salpingectomy findings and
      clinical follow-up were benign. CONCLUSION: Moderate nuclear pleomorphism and
      nuclear overlap, prominent single and multiple nucleoli and background granular
      debris were common challenging cytologic findings in fallopian tube brushings
      from low-risk patients. With experience, cellular changes can be recognized as
      benign. Recognition of the range of normal fallopian tube cytology should help to
      minimize false-positive interpretations of cytology specimens obtained in
      association with risk-reducing salpingo-oophorectomies.

PMID- 24107658
TI  - Attitudes to knee osteoarthritis and total knee replacement in Arab women: a
      qualitative study.
AB  - BACKGROUND: Total Knee Arthroplasty (TKA) is offered to patients with knee
      osteoarthritis (OA) in the oil-rich countries in the Gulf region without adequate
      understanding of their perceptions, preferences or pain experiences. This study
      aimed to explore the pain experience and mobility limitation as well as the
      patient's decision making process to undertake TKA among women with knee pain in
      the waiting list for surgery. METHODS: Five focus group discussions were
      conducted comprised of 39 women with severe knee OA from the waiting list for TKA
      in the only orthopaedic hospital in Kuwait. Discussions were recorded,
      transcribed and coded for themes to identify the factors considered to be
      important in decision-making for TKA. RESULTS: Experiencing knee pain was central
      to daily living and affected patients and their families. Mobility limitation was
      shaped by a strong sense of expected obligation to take care of the family. Two
      major sources of TKA delay were identified; one was due to late clinical advice
      to undergo TKA which was the result of receiving several consultations from
      different clinicians each of whom tried the medical management for OA. The second
      delay occurred after the clinical advice for TKA and was mainly due to
      ambivalence of patients because of fear of the operation and the lack of
      information about TKA that resulted in unclear expectations of the surgery.
      CONCLUSIONS: Both verbal and written information about TKA should be provided as
      part of preoperative rehabilitation. This is critical to improve doctor-patient
      interactions and facilitate informed decision about the procedure and thus
      achieve patient-centered healthcare.

PMID- 24107660
TI  - The progressivity of health-care financing in Kenya.
AB  - BACKGROUND: Health-care financing should be equitable. In many developing
      countries such as Kenya, changes to health-care financing systems are being
      implemented as a means of providing equitable access to health care with the aim
      of attaining universal coverage. Vertical equity means that people of dissimilar
      ability to pay make dissimilar levels of contribution to the health-care
      financing system. Vertical equity can be analysed by measuring progressivity.
      OBJECTIVES: The aim of this study was to analyse progressivity by measuring
      deviations from proportionality in the relationship between sources of health
      care financing and ability to pay using Kakwani indices applied to data from the
      Kenya Household Health Utilisation and Expenditure Survey 2007. METHODS:
      Concentration indices and Kakwani indices were obtained for the sources of health
      care financing: direct and indirect taxes, out of pocket (OOP) payments, private
      insurance contributions and contributions to the National Hospital Insurance
      Fund. The bootstrap method was used to analyse the sensitivity of the Kakwani
      index to changes in the equivalence scale or the use of an alternative measure of
      ability to pay. RESULTS: The overall health-care financing system was regressive.
      Out of pocket payments were regressive with all other payments being
      proportional. Direct taxes, indirect taxes and private insurance premiums were
      sensitive to the use of income as an alternative measure of ability to pay.
      However, the overall finding of a regressive health-care system remained.
      CONCLUSION: Reforms to the Kenyan health-care financing system are required to
      reduce dependence on out of pocket payments. The bootstrap method can be used in
      determining the sensitivity of the Kakwani index to various assumptions made in
      the analysis. Further analyses are required to determine the equity of health
      care utilization and the effect of proposed reforms on overall equity of the
      Kenyan health-care system.

PMID- 24107661
TI  - Reproducibility and validity of a quantitative FFQ designed for patients with
      type 2 diabetes mellitus from southern Brazil.
AB  - OBJECTIVE: To evaluate the reproducibility and validity of a previously
      constructed FFQ to assess the usual diet of patients with type 2 diabetes
      mellitus (T2DM). DESIGN: Cross-sectional survey using two quantitative FFQ (1
      month interval) supported by a food photograph portfolio, a 3 d weighed diet
      record (WDR) and urinary N output measurement (as a biomarker of protein intake).
      SETTING: Group of Nutrition in Endocrinology, southern Brazil. SUBJECTS: Out
      patients with T2DM. RESULTS: From a total of 104 eligible T2DM patients, eighty
      eight were included in the evaluation of FFQ reproducibility and seventy-two
      provided data for the validity study. The intakes estimated from the two FFQ did
      not differ (P > 0.05) and the correlation coefficients were significant (P <
      0.01) for energy and nutrients, ranging from 0.451 (soluble fibre) to 0.936
      (PUFA). Regarding the validity evaluation, data from the FFQ were higher than
      those from the WDR for total (28.3%), soluble (27.4%) and insoluble fibres
      (29.1%), and SFA (13.5%), MUFA (11.1 %) and total lipids (9.2%; all P < 0.05).
      There were significant correlation coefficients between the FFQ and WDR for most
      nutrients, when adjusted for energy intake and de-attenuated. Also, the Bland
      Altman plots between the FFQ and WDR for energy and macronutrient intakes showed
      that the FFQ may be used as alternative method to the WDR. The validity
      coefficient (using the method of triads) for the FFQ protein intake was 0.522
      (95% CI 0.414, 0.597). CONCLUSIONS: This quantitative FFQ was valid and precise
      to assess the usual diet of patients with T2DM, according to its validity and
      reproducibility.

PMID- 24107662
TI  - Comparison of the effects of desflurane and sevoflurane on middle ear pressure: a
      randomized controlled clinical trial.
AB  - OBJECTIVE: The aim of the present study was to compare the effects of two
      inhalation anesthetics, desflurane and sevoflurane, on middle ear pressure.
      METHODS: After we obtained written consent from the patients and the approval
      from our institutional ethical committee, we included 56 ASA I-II patients aged
      between 18 and 60 years in this study. They were randomly divided into two groups
      of 28 patients each. Desflurane 4-6% (Group D) or sevoflurane 1-2% (Group S) were
      used for anesthesia management in patients. Baseline tympanometry was carried out
      and recorded before the induction of anesthesia on both ears, and 3 more
      measurements were done and recorded 5, 15 and 30 min after induction. RESULTS: In
      both groups, middle ear pressure values were found to be significantly elevated
      when compared to baseline measurements (p < 0.05). When middle ear pressure was
      compared between the groups, no difference was found between the values obtained
      at baseline and at 5 min in Group S, while especially the values obtained at 15
      min revealed significantly higher middle ear pressures in Group D. CONCLUSION: It
      was observed that the increase in middle ear pressure caused by sevoflurane was
      significantly lower than that caused by desflurane.

PMID- 24107663
TI  - What matters is not only how often but also how much blood pressure rises.
      Limitations of blood pressure load.

PMID- 24107664
TI  - The challenge of preventing dementia by antihypertensive treatment.

PMID- 24107665
TI  - Renal nerve ablation as a tool for studying the interactions between arterial
      stiffness, blood pressure and sympathetic drive: weight of the evidence.

PMID- 24107659
TI  - Nutrition therapy recommendations for the management of adults with diabetes.
AB  - There is no standard meal plan or eating pattern that works universally for all
      people with diabetes. In order to be effective, nutrition therapy should be
      individualized for each patient/client based on his or her individual health
      goals; personal and cultural preferences; health literacy and numeracy; access to
      healthful choices; and readiness, willingness, and ability to change. Nutrition
      interventions should emphasize a variety of minimally processed nutrient dense
      foods in appropriate portion sizes as part of a healthful eating pattern and
      provide the individual with diabetes with practical tools for day-to-day food
      plan and behavior change that can be maintained over the long term.

PMID- 24107666
TI  - A cautious view of the relationship between ambulatory blood pressure monitoring
      data and salt-sensitivity of blood pressure.

PMID- 24107667
TI  - A cautious view of the relationship between ambulatory blood pressure monitoring
      data and salt-sensitivity of blood pressure. Reply.

PMID- 24107668
TI  - A cautious view of the relationship between ambulatory blood pressure monitoring
      data and salt-sensitivity of blood pressure. Reply.

PMID- 24107669
TI  - Isolated systolic hypertension in the young: a need for clarity.

PMID- 24107670
TI  - Isolated systolic hypertension in the young: a need for clarity. Reply.

PMID- 24107671
TI  - Investigating the association between creatine kinase and failure of
      antihypertensive treatment: much to be thought of in the everyday clinical
      setting.

PMID- 24107672
TI  - Investigating the association between creatine kinase and failure of
      antihypertensive treatment: much to be thought of in the everyday clinical
      setting.

PMID- 24107673
TI  - Exercise-induced platelet activation in essential hypertension: have we solved
      the puzzle?

PMID- 24107674
TI  - Exercise-induced platelet activation in essential hypertension: have we solved
      the puzzle? Reply.

PMID- 24107675
TI  - Effects of hypertension and antihypertensive therapy on sexual function in the
      elderly: the jury is still out.

PMID- 24107676
TI  - Effects of hypertension and antihypertensive therapy on sexual function in the
      elderly: the jury is still out. Reply.

PMID- 24107677
TI  - Effect of current smoking and blood pressure on cardiovascular events and
      mortality for workers: number of events for multivariate analysis to keep
      validity.

PMID- 24107678
TI  - Effect of current smoking and blood pressure on cardiovascular events and
      mortality for workers: number of events for multivariate analysis to keep
      validity. Reply.

PMID- 24107680
TI  - Cognitive assessment in elderly residents of long-stay institutions.
AB  - OBJECTIVE: To evaluate the cognitive performance of institutionalized elderly in
      the city of Natal, state of Rio Grande do Norte, Brazil. METHODS: A descriptive,
      longitudinal study of 85 aged individuals via an interview conducted following
      the application of a classification form and the Mini-Mental State Examination
      (MMSE), with different cutoff points according to the level of education. The
      study was approved by the Research Ethics Committee of the Universidad Federal do
      Rio Grande do Norte (164/2011). RESULTS: The mean age of the elderly studied was
      76.8 years, 48.3% were single and 62.0% women, with an average of 3.27 children
      and 3 years of schooling; cognitive losses were recorded over a 6-month period
      following the 1st assessment, declining from 18.8 to 16.9% at the 2nd assessment
      for the following items: orientation to space (p = 0.02), language (p = 0.02) and
      repetition (p = 0.01). CONCLUSION: The results show significant cognitive changes
      among elderly subjects, with 64.6% exhibiting cognitive impairment. The findings
      suggest systematic evaluations in elders as a mean to establish prevention
      measures for health losses, taking into account that the referred deficits are
      capable of causing damage in the everyday life of these elderly residents of
      institutions.

PMID- 24107679
TI  - Novel approach to estimate kidney and cyst volumes using mid-slice magnetic
      resonance images in polycystic kidney disease.
AB  - OBJECTIVE: To evaluate whether kidney and cyst volumes can be accurately
      estimated based on limited area measurements from magnetic resonance (MR) images
      of patients with autosomal dominant polycystic kidney disease (ADPKD). MATERIALS
      AND METHODS: MR coronal images of 178 ADPKD participants from the Consortium for
      Radiologic Imaging Studies of ADPKD (CRISP) were analyzed. For each MR image
      slice, we measured kidney and renal cyst areas using stereology and region-based
      thresholding methods, respectively. The kidney and cyst 'observed' volumes were
      calculated by summing up the area measurements of all the slices covering the
      kidney. To estimate the volume, we selected a coronal mid-slice in each kidney
      and multiplied its area by the total number of slices ('PANK2' for kidney and
      'PANC2' for cyst). We then compared the kidney and cyst volumes predicted from
      PANK2 and PANC2, respectively, to the corresponding observed volumes, using a
      linear regression analysis. RESULTS: The kidney volume predicted from PANK2
      correlated extremely well with the observed kidney volume (R(2) = 0.994 for the
      right kidney and 0.991 for the left kidney). The linear regression coefficient
      multiplier to PANK2 that best fit the kidney volume was 0.637 (95% CI: 0.629
      0.644) for the right kidney and 0.624 (95% CI: 0.616-0.633) for the left kidney.
      The correlation between the cyst volume predicted from PANC2 and the observed
      cyst volume was also very high (R(2) = 0.984 for the right kidney and 0.967 for
      the left kidney). The least squares linear regression coefficient for PANC2 was
      0.637 (95% CI: 0.624-0.649) for the right kidney and 0.608 (95% CI: 0.591-0.625)
      for the left kidney. CONCLUSION: Kidney and cyst volumes can be closely
      approximated by multiplying the product of the mid-slice area measurement and the
      total number of slices in the coronal MR images of ADPKD kidneys by 0.61-0.64.
      This information will help save processing time needed to estimate total kidney
      and cyst volumes of ADPKD kidneys.

PMID- 24107681
TI  - The procyonid social club: comparison of brain volumes in the coatimundi (Nasua
      nasua, N. narica), kinkajou (Potos flavus), and raccoon (Procyon lotor).
AB  - The present study investigated whether increased relative brain size, including
      regional brain volumes, is related to differing behavioral specializations
      exhibited by three member species of the family Procyonidae. Procyonid species
      exhibit continuums of behaviors related to social and physical environmental
      complexities: the mostly solitary, semiarboreal and highly dexterous raccoons
      (Procyon lotor); the exclusively arboreal kinkajous (Potos flavus), which live
      either alone or in small polyandrous family groups, and the social, terrestrial
      coatimundi (Nasua nasua, N. narica). Computed tomographic (CT) scans of 45 adult
      skulls including 17 coatimundis (9 male, 8 female), 14 raccoons (7 male, 7
      female), and 14 kinkajous (7 male, 7 female) were used to create three
      dimensional virtual endocasts. Endocranial volume was positively correlated with
      two separate measures of body size: skull basal length (r = 0.78, p < 0.01) and
      basicranial axis length (r = 0.45, p = 0.002). However, relative brain size
      (total endocranial volume as a function of body size) varied by species depending
      on which body size measurement (skull basal length or basicranial axis length)
      was used. Comparisons of relative regional brain volumes revealed that the
      anterior cerebrum volume consisting mainly of frontal cortex and surface area was
      significantly larger in the social coatimundi compared to kinkajous and raccoons.
      The dexterous raccoon had the largest relative posterior cerebrum volume, which
      includes the somatosensory cortex, in comparison to the other procyonid species
      studied. The exclusively arboreal kinkajou had the largest relative cerebellum
      and brain stem volume in comparison to the semi arboreal raccoon and the
      terrestrial coatimundi. Finally, intraspecific comparisons failed to reveal any
      sex differences, except in the social coatimundi. Female coatimundis possessed a
      larger relative frontal cortical volume than males. Social life histories differ
      in male and female coatimundis but not in either kinkajous or raccoons. This
      difference may reflect the differing social life histories experienced by females
      who reside in their natal bands, and forage and engage in antipredator behavior
      as a group, while males disperse upon reaching adulthood and are usually solitary
      thereafter. This analysis in the three procyonid species supports the comparative
      neurology principle that behavioral specializations correspond to an expansion of
      neural tissue involved in that function.

PMID- 24107682
TI  - Functional analysis of purine nucleoside phosphorylase as a key enzyme in
      ribavirin metabolism.
AB  - Ribavirin is a purine nucleoside analogue that possesses potent anti-hepatitis C
      virus activity, and it has long been considered likely that ribavirin undergoes a
      first-pass metabolism at the small intestine. Although purine nucleoside
      phosphorylase (PNP) is assumed to be involved in this metabolism, this has not
      been conclusively demonstrated. Furthermore, no pharmacogenomic studies related
      to PNP-mediated ribavirin phosphorolysis have previously been conducted. In this
      study, we sought to identify the role of PNP in ribavirin phosphorolysis in the
      human small intestine, and to clarify the effect of the single nucleotide
      polymorphism (rs1049564) on PNP's ribavirin phosphorolysis activity. The results
      of our investigations show that PNP is abundantly expressed in the human small
      intestine, and that intestinal ribavirin phosphorolysis is severely inhibited by
      ganciclovir, a PNP-inhibitor. Therefore, PNP is likely to play a primary role in
      the ribavirin phosphorolysis in the human small intestine. On the other hand, the
      results of our attempt to clarify the function of rs1049564 show that it does not
      affect PNP's ribavirin phosphorolysis activity. We believe that the present study
      will facilitate further pharmacogenomic and biochemical characterization of PNP
      as a key metabolic enzyme of ribavirin.

PMID- 24107683
TI  - Floral adaptation to local pollinator guilds in a terrestrial orchid.
AB  - BACKGROUND AND AIMS: Studies of local floral adaptation in response to
      geographically divergent pollinators are essential for understanding floral
      evolution. This study investigated local pollinator adaptation and variation in
      floral traits in the rewarding orchid Gymnadenia odoratissima, which spans a
      large altitudinal gradient and thus may depend on different pollinator guilds
      along this gradient. METHODS: Pollinator communities were assessed and reciprocal
      transfer experiments were performed between lowland and mountain populations.
      Differences in floral traits were characterized by measuring floral morphology
      traits, scent composition, colour and nectar sugar content in lowland and
      mountain populations. KEY RESULTS: The composition of pollinator communities
      differed considerably between lowland and mountain populations; flies were only
      found as pollinators in mountain populations. The reciprocal transfer experiments
      showed that when lowland plants were transferred to mountain habitats, their
      reproductive success did not change significantly. However, when mountain plants
      were moved to the lowlands, their reproductive success decreased significantly.
      Transfers between populations of the same altitude did not lead to significant
      changes in reproductive success, disproving the potential for population-specific
      adaptations. Flower size of lowland plants was greater than for mountain flowers.
      Lowland plants also had significantly higher relative amounts of aromatic floral
      volatiles, while the mountain plants had higher relative amounts of other floral
      volatiles. The floral colour of mountain flowers was significantly lighter
      compared with the lowland flowers. CONCLUSIONS: Local pollinator adaptation
      through pollinator attraction was shown in the mountain populations, possibly due
      to adaptation to pollinating flies. The mountain plants were also observed to
      receive pollination from a greater diversity of pollinators than the lowland
      plants. The different floral phenotypes of the altitudinal regions are likely to
      be the consequence of adaptations to local pollinator guilds.

PMID- 24107684
TI  - A pollinator shift explains floral divergence in an orchid species complex in
      South Africa.
AB  - BACKGROUND AND AIMS: Floral diversification driven by shifts between pollinators
      has been one of the key explanations for the radiation of angiosperms. According
      to the Grant-Stebbins model of pollinator-driven speciation, these shifts result
      in morphologically distinct 'ecotypes' which may eventually become recognizable
      as species. The current circumscription of the food-deceptive southern African
      orchid Eulophia parviflora encompasses a highly variable monophyletic species
      complex. In this study, two forms were identified within this complex that differ
      in distribution, floral morphology, scent chemistry and phenology, and a test was
      made of whether these differences represent adaptations for different
      pollinators. METHODS AND RESULTS: Multivariate analysis of floral and vegetative
      traits revealed that there are at least two discrete morphological forms in the
      species complex. Field observations revealed that each form is pollinated by a
      different insect species, and thus represent distinct ecotypes. The early
      flowering coastal form which has long spurs and floral scent dominated by
      sesquiterpene compounds is pollinated exclusively by the long-tongued bee
      Amegilla fallax (Apidae, Anthophorinae), while the late-flowering inland form
      with short spurs and floral scent dominated by benzenoid compounds is pollinated
      exclusively by the beetle Cyrtothyrea marginalis (Cetoniinae; Scarabaeidae).
      Choice experiments in a Y-maze olfactometer showed that beetles are
      preferentially attracted to the scent of the short-spurred form. A spur
      shortening experiment showed that long spurs are required for effective
      pollination of the bee-pollinated form. Although it was initially thought likely
      that divergence occurred across a geographical pollinator gradient, plants of the
      long-spurred form were effectively pollinated when transplanted to an inland
      locality outside the natural coastal range of this form. Thus, the underlying
      geographical basis for the evolution of ecotypes in the E. parviflora complex
      remains uncertain, although early flowering in the long-spurred form to exploit
      the emergence of naive bees may restrict this form to coastal areas where there
      is no frost that would damage flower buds. Later flowering of the short-spurred
      form coincides closely with the emergence of the pollinating beetles following
      winter frosts. CONCLUSIONS: This study identifies a shift between bee and beetle
      pollination as the main driver of floral divergence in an orchid species complex.
      Floral scent and spur length appear to be key traits in mediating this
      evolutionary transition.

PMID- 24107685
TI  - Medication calculation: the potential role of digital game-based learning in
      nurse education.
AB  - Medication dose calculation is one of several medication-related activities that
      are conducted by nurses daily. However, medication calculation skills appear to
      be an area of global concern, possibly because of low numeracy skills, test
      anxiety, low self-confidence, and low self-efficacy among student nurses. Various
      didactic strategies have been developed for student nurses who still lack basic
      mathematical competence. However, we suggest that the critical nature of these
      skills demands the investigation of alternative and/or supplementary didactic
      approaches to improve medication calculation skills and to reduce failure rates.
      Digital game-based learning is a possible solution because of the following
      reasons. First, mathematical drills may improve medication calculation skills.
      Second, games are known to be useful during nursing education. Finally,
      mathematical drill games appear to improve the attitudes of students toward
      mathematics. The aim of this article was to discuss common challenges of
      medication calculation skills in nurse education, and we highlight the potential
      role of digital game-based learning in this area. 

PMID- 24107686
TI  - Prevalence, trends and associated socio-economic factors of obesity in South
      Asia.
AB  - AIM: Worldwide obesity levels have increased unprecedentedly over the past couple
      of decades. Although the prevalence, trends and associated socio-economic factors
      of the condition have been extensively reported in Western populations, less is
      known regarding South Asian populations. METHODS: A review of articles using
      Medline with combinations of the MeSH terms: 'Obesity', 'Overweight' and
      'Abdominal Obesity' limiting to epidemiology and South Asian countries. RESULTS:
      Despite methodological heterogeneity and variation according to country, area of
      residence and gender , the most recent nationally representative and large
      regional data demonstrates that without any doubt there is a epidemic of obesity,
      overweight and abdominal obesity in South Asian countries. Prevalence estimates
      of overweight and obesity (based on Asian cut-offs: overweight >= 23 kg/m2,
      obesity >= 25 kg/m2) ranged from 3.5% in rural Bangladesh to over 65% in the
      Maldives. Abdominal obesity was more prevalent than general obesity in both sexes
      in this ethnic group. Countries with the lowest prevalence had the highest upward
      trend of obesity. Socio-economic factors associated with greater obesity in the
      region included female gender, middle age, urban residence, higher educational
      and economic status. CONCLUSION: South Asia is significantly affected by the
      obesity epidemic. Collaborative public health interventions to reverse these
      trends need to be mindful of many socio-economic constraints in order to provide
      long-term solutions.

PMID- 24107687
TI  - External quality control of cervical cytopathology: interlaboratory variability.
AB  - OBJECTIVE: To compare the variability of screening tests held at laboratories
      with the Unit for External Quality Control (UEQC), checking the frequency of
      cases that were discordant, false-positive, false-negative, unsatisfactory or
      that had a delay in clinical management and diagnostic agreement. MATERIALS AND
      METHODS: The study analyzed 10,053 screening tests from January 2007 to December
      2008, including all positive cases, all those that fall under unsatisfactory and
      at least 10% of negative screening tests. The magnitude of the agreement was
      analyzed using the kappa coefficient. RESULTS: Out of the 10,053 cases analyzed,
      7.59% were considered disagreeing, and it was estimated that 1.1% were false
      negative. There was a delay in the clinical procedure regarding 2.44% cases.
      There were 2.82% of cases identified as false-positive and 1.24% as
      unsatisfactory. The diagnostic agreement was excellent (kappa = 0.81). The
      agreement of most laboratories concerning screening tests was classified as very
      good. The agreement of the sample adequacy was reasonable (kappa = 0.30) and the
      agreement regarding the representation of epithelia was considered excellent.
      CONCLUSION: Most laboratories showed very good agreement; however, it is worthy
      of note that to establish the standardization of diagnostic criteria, and enhance
      the accuracy of screening and improve the quality of cytopathology test results,
      it is necessary to perform external quality control.

PMID- 24107688
TI  - Heart failure: advances and issues.

PMID- 24107689
TI  - Comparison of left internal mammary artery diameter before and after left
      stellate ganglion block.
AB  - AIMS AND OBJECTIVES: Left internal mammary artery (LIMA) is the preferred
      arterial conduit for coronary artery bypass grafting. Various pharmacological
      agents are known to increase LIMA blood flow. Sympathetic blockade mediated by
      stellate ganglion block (SGB) has been used to provide vasodilatation in the
      upper extremities and in the treatment of refractory angina. We investigated
      effect of left stellate ganglion block (LSGB) on LIMA diameter. MATERIALS AND
      METHODS: In 30 diagnosed patients of triple vessel coronary artery disease, LSGB
      was given under fluoroscopic guidance by C6 transverse process approach using 10
      ml of 1% lignocaine. LIMA diameter was measured before and 20 min after the block
      at 2 nd , 3 rd , 4 th and at 5 th rib level. Heart rate (HR), systolic blood
      pressure (SBP), diastolic blood pressure (DBP) and mean arterial pressure (MAP)
      were recorded before and 20 min after the block. RESULTS: The LIMA diameter
      increased significantly at 2 nd (2.56 +/- 0.39 vs. 2.99 +/- 0.40; P < 0.0001), 3
      rd (2.46 +/- 0.38 vs. 2.90 +/- 0.40; P < 0.0001), 4 th (2.39 +/- 0.38 vs. 2.84 +/
      0.41; P < 0.0001) and 5 th rib level (2.35 +/- 0.38 vs. 2.78 +/- 0.40; P <
      0.0001). No statistically significant change occurred in HR, SBP, DBP and MAP
      before and 20 min after LSGB. CONCLUSIONS: LSGB significantly increased the LIMA
      diameter. The LSGB can be considered as an alternative to topical and systemic
      vasodilators for reducing vasospasm of LIMA.

PMID- 24107690
TI  - Influence of ethanol-induced pulmonary embolism on hemodynamics in pigs.
AB  - AIMS AND OBJECTIVES: Ethanol is widely used for the embolization treatment of
      vascular malformations, but it can also cause serious complications such us
      pulmonary hypertension, cardiopulmonary collapse and death. The complications are
      considered secondary to pulmonary vasospasm and ethanol-induced sludge embolism,
      etc., We studied the hemodynamic effects of intravenous absolute ethanol
      injection and ethanol sludge injection in pigs. MATERIALS AND METHODS: A total of
      5 pigs underwent intravenous injection of ex vivo generated ethanol-induced
      sludge in which residual ethanol was removed (Group S) and 4 pigs underwent
      intravenous injection of absolute ethanol (Group E). Hemodynamic parameters
      related to the pulmonary and systemic circulation were compared between the
      groups. RESULTS: Transient pulmonary hypertension was observed in both groups and
      the hemodynamic changes were similar in both groups. CONCLUSIONS: Sludge can
      induce transient pulmonary hypertension or cardiopulmonary collapse, without
      ethanol and may be the mechanism by which ethanol induces its adverse hemodynamic
      effects.

PMID- 24107691
TI  - Anesthesia for gastrointestinal endoscopy in patients with left ventricular
      assist devices: initial experience with 68 procedures.
AB  - AIMS AND OBJECTIVES: Continuous flow left ventricular assist devices (LVAD) have
      emerged as a reliable treatment option for heart failure. Because of bleeding
      secondary to anticoagulation, these patients present frequently for
      gastrointestinal (GI) endoscopy. The presently available literature on
      perioperative management of these patients is extremely limited and is primarily
      based upon theoretical principles. MATERIALS AND METHODS: Perioperative records
      of patients with LVAD undergoing (GI) endoscopy between 2008 and 2012 were
      reviewed. Patient, device and procedure specific information was analyzed.
      RESULTS: A total of 105 LVADs were implanted, and 68 procedures were performed in
      39 patients. The most common indication was GI bleed (48/68), with yearly risk of
      8.57% per patient. A total of 63 procedures were performed under deep sedation,
      with five procedures requiring general anesthesia. Intra-procedure hypotension
      was managed by fluids and (or) vasopressors/inotropes (phenylephrine, ephedrine
      or milrinone) guided by plethysmographic waveform, non-invasive blood pressure
      (NIBP) and LVADs pulsatility index (for HeartMate II)/flow pulsatility (for
      HeartWare). No patient required invasive monitoring and both NIBP and pulse
      oximeter could be reliably used for monitoring (and guided management) in all
      patients due to the presence of native heart's pulsatile output. CONCLUSION: In
      the presence of residual heart function, with optimal device settings, non
      invasive hemodynamic monitoring can be reliably used in these patients while
      undergoing GI endoscopy under general anesthesia or monitored anesthesia care.
      Transient hypotensive episodes respond well to fluids/vasopressors without the
      need of increasing device speed that can be detrimental.

PMID- 24107692
TI  - Management issues during HeartWare left ventricular assist device implantation
      and the role of transesophageal echocardiography.
AB  - Left ventricular assist devices (LVAD) are increasingly used for mechanical
      circulatory support of patients with severe heart failure, primarily as a bridge
      to heart transplantation. Transesophageal echocardiography (TEE) plays a major
      role in the clinical decision making during insertion of the devices and in the
      post-operative management of these patients. The detection of structural and
      device-related mechanical abnormalities is critical for optimal functioning of
      assist device. In this review article, we describe the usefulness of TEE for
      optimal perioperative management of patients presenting for HeartWare LVAD
      insertion. 

PMID- 24107693
TI  - Practice guidelines for perioperative transesophageal echocardiography:
      recommendations of the Indian association of cardiovascular thoracic
      anesthesiologists.
AB  - Transoesophageal Echocardiography (TEE) is now an integral part of practice of
      cardiac anaesthesiology. Advances in instrumentation and the information that can
      be obtained from the TEE examination has proceeded at a breath-taking pace since
      the introduction of this technology in the early 1980s. Recognizing the
      importance of TEE in the management of surgical patients, the American Societies
      of Anesthesiologists (ASA) and the Society of Cardiac Anesthesiologists, USA
      (SCA) published practice guidelines for the clinical application of perioperative
      TEE in 1996. On a similar pattern, Indian Association of Cardiac
      Anaesthesiologists (IACTA) has taken the task of putting forth guidelines for
      transesophageal echocardiography (TEE) to standardize practice across the
      country. This review assesses the risks and benefits of TEE for several
      indications or clinical scenarios. The indications for this review were drawn
      from common applications or anticipated uses as well as current clinical practice
      guidelines published by various society practicing Cardiac Anaesthesia and
      cardiology . Based on the input received, it was determined that the most
      important parts of the TEE examination could be displayed in a set of 20 cross
      sectional imaging planes. These 20 cross sections would provide also the format
      for digital acquisition and storage of a comprehensive TEE examination. Because
      variability exists in the precise anatomic orientation between the heart and the
      esophagus in individual patients, an attempt was made to provide specific
      criteria based on identifiable anatomic landmarks to improve the reproducibility
      and consistency of image acquisition for each of the standard cross sections. 

PMID- 24107694
TI  - Cardiomegaly due to left atrial enlargement mimicking dextrocardia in chest
      radiograph.

PMID- 24107695
TI  - A dangerous communication.

PMID- 24107697
TI  - Coronary artery bypass surgery in the presence of cerebrospinal fluid rhinorrhea.
AB  - A seventy eight year old male patient was admitted in our hospital with headache,
      vomiting, irritability and confusion. Initially he was diagnosed as a case of
      pyogenic encephalitis. Further investigations revealed that patient had
      cerebrospinal fluid rhinorrhea and coronary artery disease. He successfully
      underwent coronary artery bypass grafting and cerebrospinal fluid leak repair. 

PMID- 24107698
TI  - Anesthetic and hemodynamic management of a rare case of Brucella multivalvular
      endocarditis in cardiogenic shock undergoing emergency aortic valve replacement
      and mitral valve repair.
AB  - We describe a very rare case of human brucella multivalvular endocarditis.
      Patient presented in a state of cardiogenic shock with low urine output and a
      history of breathlessness. Patient was diagnosed to have brucellosis 2 months
      back by blood cultures and agglutination tests and was receiving doxycycline and
      rifampicin therapy. Echocardiography showed severe aortic regurgitation, moderate
      mitral regurgitation, severe left ventricular dysfunction and a mobile vegetation
      attached to the aortic valve. Patient was scheduled for emergency surgery; while
      preparing for surgery hemodynamic monitoring, non-invasive ventilation and
      inotropic supports were started. During surgery, the aortic valve was found
      perforated and the aortomitral continuity was disrupted. Aortic valve replacement
      and mitral valve repair were performed. Hemofiltration was used during
      cardiopulmonary bypass. Weaning from bypass was achieved with the help of
      inodilators, dual chamber pacing and intra-aortic balloon pump. 

PMID- 24107699
TI  - Posterior mediastinal mass: do we need to worry much?
AB  - Anesthetic management of mediastinal masses is challenging. There is abundant
      literature available on anesthesia management of anterior mediastinal mass.
      Anesthetic management of posterior mediastinal mass lesions normally have
      uneventful course. We describe airway collapse and difficult mechanical
      ventilation in the postoperative period in a patient with posterior mediastinal
      mass. 

PMID- 24107700
TI  - Primary malignant fibrous histiocytoma involving the left pulmonary vein
      presenting as a left atrial tumor.
AB  - A 35-year-old woman presented with 4 months history of progressively increasing
      intermittent dyspnea and hemoptysis. Transthoracic echocardiography revealed a
      loculated mass in the left atrium (LA). A provisional diagnosis of LA myxoma was
      made. Intraoperatively the tumor was found extending into and closely adherent to
      the left pulmonary vein and could not be completely cleared off from the
      pulmonary venous wall. The histopathological examination of the tumor revealed it
      to be a myxoid malignant fibrous histiocytoma. 

PMID- 24107701
TI  - Use of optimized ultrasound axis along with marked introducer needle to prevent
      mechanical complications of internal jugular vein catheterization.
AB  - Internal jugular vein (IJV) catheterization is a routine technique in the
      intensive care unit. Ultrasound (US) guided central venous catheter (CVC)
      insertion is now the recommended standard. However, mechanical complications
      still occur due to non-visualization of the introducer needle tip during US
      guidance. This may result in arterial or posterior venous wall puncture or
      pneumothorax. We describe a new technique of (IJV) catheterization using US,
      initially the depth of the IJV from the skin is measured in short-axis and then
      using real time US long-axis view guidance a marked introducer needle is advanced
      towards the IJV to the defined depth measured earlier in the short axis and the
      IJV is identified, assessed and cannulated for the CVC insertion. Our technique
      is simple and may reduce mechanical complications of US guided CVC insertion. 

PMID- 24107702
TI  - In response to, "The application of European system for cardiac operative risk
      evaluation II and society of thoracic surgeons risk score for risk stratification
      in Indian patients undergoing cardiac surgery".

PMID- 24107703
TI  - Interesting facts about chest radiograph.

PMID- 24107704
TI  - Transesophageal echocardiography images of right ventricular sarcoma.

PMID- 24107705
TI  - Anterior mitral leaflet myxoma: a rare occurrence.

PMID- 24107706
TI  - Global left and right ventricular dysfunction after tranexamic acid
      administration in a polytrauma patient.

PMID- 24107707
TI  - Spt6: two fundamentally distinct functions in the regulation of histone
      modification.
AB  - As posttranslational modifications of histones H3 and H4 determine the state of
      chromatin in cis, these histones should remain attached to template DNA during
      transcription in order to maintain the state of chromatin. RNA polymerase II
      itself can transcribe the nucleosome template without changing nucleosome
      positioning. However, it was uncertain whether Spt6, a highly conserved
      polymerase-associated histone chaperone, prevents "preexisting" histone molecules
      from being dissociated from template DNA during transcription. We recently showed
      that Spt6 prevents transcription-coupled loss of posttranslationally modified
      histone H3. Taking previous studies into account, we would like to propose here
      that Spt6 has two fundamentally distinct functions in the regulation of histone
      modification: one is to act as a platform for histone modifiers and the other is
      to act as a molecular liaison between histone molecules and template DNA to
      prevent cotranscriptional dissociation of preexisting histones in order to
      maintain locus-specific modifications. 

PMID- 24107708
TI  - High prevalence rate of left superior vena cava determined by echocardiography in
      patients with congenital heart disease in Saudi Arabia.
AB  - BACKGROUND: Persistent left superior vena cava (LSVC) is one of the common
      anomalies of the systemic veins. Its prevalence is 0.1-0.3% in the general
      population and is more common with congenital heart disease (CHD). The importance
      of detecting persistent LSVC prior to cardiac surgery is paramount for systemic
      veins cannulations. AIM: The aim was to evaluate the prevalence of persistent
      LSVC in patients with CHD in Saudi Arabia. METHODS: All patients referred to our
      institution had echocardiography. All complete studies were reviewed for the
      presence of persistent LSVC. A computerized database was created including the
      demographic data, CHD diagnoses, and the presence of persistent LSVC. RESULTS: A
      total of 2,042 were examined with an age range of 1 day to 16 years. The complete
      echocardiographic studies were 1,832 (90%) of whom 738 (40%) patients had CHD.
      The prevalence of persistent LSVC in patients with CHD was 7.8% (OR 9.26, 95% CI
      4.7-18.2, p<0.001). The most common cardiac defect associated with persistent
      LSVC was complete atrioventricular septal defect (AVSD); all patients with AVSD
      had Down syndrome. The total number of patients with AVSD was 41, and persistent
      LSVC was found in 11 (26%) of them (odds ratio 5.1, 95% CI 2.4-10.8, p<0.001).
      CONCLUSIONS: The prevalence of persistent LSVC in the current population is
      almost double the reported prevalence obtained using the same echocardiographic
      screening tool.

PMID- 24107709
TI  - Judging the behavior of people we know: objective assessment, confirmation of
      preexisting views, or both?
AB  - The present study investigates the relative extent to which judgments of people's
      behavior are influenced by "truth" (as measured by averaged observer-judgments)
      and by systematic bias (i.e., perceivers' preexisting views of target persons).
      Using data from online questionnaires and laboratory sessions (N = 155), we
      demonstrate that self- and peer-judgments of people's actual behavior in specific
      situations are somewhat accurate but are also affected by what perceivers thought
      of the targets before observing their behavior. The latter effect comprises a
      general evaluative component (generally positive or negative views of targets)
      and a content-specific component (views of targets in terms of specific
      characteristics, for example, "restrained"). We also found that friends, but not
      targets themselves, tend to judge targets' behaviors more positively than
      unacquainted observers do. The relevance of these findings for person perception
      in everyday life and in research contexts is discussed. 

PMID- 24107710
TI  - The role of locus of control in daily life.
AB  - Conceived of as a stable trait, locus of control has been linked with
      psychological and physical health outcomes. We investigated whether locus of
      control operates as a state variable, whether variation in daily locus of control
      is associated with anxiety and stressful events, and whether it predicts daily
      health behaviors and symptoms. Using a daily diary study of pregnant couples, we
      found daily variation in locus of control was predicted by daily hassles and
      anxiety such that high same-day and previous-day anxiety and hassles were
      associated with reports of lower levels of control. Furthermore, daily locus of
      control was positively associated with positive health behaviors and predicted
      negative health symptoms. These results provide evidence for a social learning
      perspective on the development and maintenance of individuals' sense of control
      and suggest that locus of control should be considered both a state- and trait
      level construct in future research. 

PMID- 24107711
TI  - PolyCTLDesigner: a computational tool for constructing polyepitope T-cell
      antigens.
AB  - BACKGROUND: Construction of artificial polyepitope antigens is one of the most
      promising strategies for developing more efficient and safer vaccines evoking T
      cell immune responses. Epitope rearrangements and utilization of certain spacer
      sequences have been proven to greatly influence the immunogenicity of polyepitope
      constructs. However, despite numerous efforts towards constructing and evaluating
      artificial polyepitope immunogens as well as despite numerous computational
      methods elaborated to date for predicting T-cell epitopes, peptides binding to
      TAP and for antigen processing prediction, only a few computational tools were
      currently developed for rational design of polyepitope antigens. FINDINGS: Here
      we present a PolyCTLDesigner program that is intended for constructing
      polyepitope immunogens. Given a set of either known or predicted T-cell epitopes
      the program selects N-terminal flanking sequences for each epitope to optimize
      its binding to TAP (if necessary) and joins resulting oligopeptides into a
      polyepitope in a way providing efficient liberation of potential epitopes by
      proteasomal and/or immunoproteasomal processing. And it also tries to minimize
      the number of non-target junctional epitopes resulting from artificial
      juxtaposition of target epitopes within the polyepitope. For constructing
      polyepitopes, PolyCTLDesigner utilizes known amino acid patterns of TAP-binding
      and proteasomal/immunoproteasomal cleavage specificity together with genetic
      algorithm and graph theory approaches. The program was implemented using Python
      programming language and it can be used either interactively or through
      scripting, which allows users familiar with Python to create custom pipelines.
      CONCLUSIONS: The developed software realizes a rational approach to designing
      poly-CTL-epitope antigens and can be used to develop new candidate polyepitope
      vaccines. The current version of PolyCTLDesigner is integrated with our TEpredict
      program for predicting T-cell epitopes, and thus it can be used not only for
      constructing the polyepitope antigens based on preselected sets of T-cell
      epitopes, but also for predicting cytotoxic and helper T-cell epitopes within
      selected protein antigens. PolyCTLDesigner is freely available from the project's
      web site: http://tepredict.sourceforge.net/PolyCTLDesigner.html.

PMID- 24107712
TI  - Design strategies of hybrid metallic nanoparticles for theragnostic applications.
AB  - Metallic nanoparticles (MNPs) such as iron oxide and gold nanoparticles are
      interesting platforms to build theragnostic nanocarriers which combine both
      therapeutic and diagnostic functions within a single nanostructure. Nevertheless,
      their surface must be functionalized to be suitable for in vivo applications.
      Surface functionalization also provides binding sites for targeting ligands, and
      for drug loading. This review focuses on the materials and surface chemistry used
      to build hybrid nanocarriers that are inorganic cores functionalized with organic
      materials. The surface state of the MNPs largely depends on their synthesis
      routes, and dictates the strategies used for functionalization. Two main
      strategies can be found in the literature: the design of core-shell nanosystems,
      or embedding nanoparticles in organic materials. Emerging tendencies such as the
      use of clusters or alternative coating materials are also described. To present
      both hydrophilic and lipophilic nanosystems, we chose the doxorubicin anticancer
      agent as an example, as the molecule presents an affinity for both types of
      materials. 

PMID- 24107713
TI  - Tetramethylpyrazine analogue CXC195 protects against cerebral
      ischemia/reperfusion injury in the rat by an antioxidant action via inhibition of
      NADPH oxidase and iNOS expression.
AB  - AIMS: This study was conducted to investigate the protective effects of CXC195, a
      tetramethylpyrazine analogue, in acute focal cerebral ischemia/reperfusion (I/R)
      injury in rats and to elucidate the potential mechanism. METHODS: Middle cerebral
      artery occlusion for 2 h followed by reperfusion for 24 h was conducted in male
      Wistar rats and different doses of tetramethylpyrazine and CXC195 were
      intraperitoneally injected at 30 min after reperfusion. RESULTS: Our results
      demonstrated that CXC195 at the dosage of 3 and 10 mg/kg significantly reduced
      the neurological deficit score and the infarct volume compared to the vehicle
      treated group. In addition, CXC195 exhibited a protective effect against
      hippocampus neuronal cell death and significantly restored the brain ATP content.
      The activities of superoxide dismutase (SOD), glutathione peroxidase (GPx) and
      total antioxidative capability (T-AOC), as well as production of malondialdehyde
      (MDA) and reactive oxygen species (ROS) were assayed in ipsilateral hemisphere
      homogenates to evaluate the redox status after I/R injury. Treatment with CXC195
      significantly attenuated the decrease of SOD, GPx and T-AOC activities and
      inhibited the elevation of MDA content and ROS generation. Furthermore, CXC195
      prevented the upregulation of the NADPH oxidase (NOX) 2 and NOX4, and reduced
      inducible nitric oxide synthase (iNOS) induction and production of nitric oxide
      induced by I/R. CONCLUSION: These results suggest that CXC195 has a
      neuroprotective effect in transient focal ischemia, which is most likely due to
      its antioxidant activity by inhibiting NOX and iNOS expression.

PMID- 24107714
TI  - Study of corneal copper deposits in Wilson's disease by in vivo confocal
      microscopy.
AB  - PURPOSE: To study corneal copper deposits in Wilson's disease (WD) patients by
      traditional biomicroscopy and in vivo laser scanning confocal microscopy (LSCM).
      METHODS: Twenty WD patients and 20 matched controls underwent an ophthalmic
      examination in one eye randomly chosen, including slit lamp biomicroscopy with
      Goldmann's three-mirror contact lens examination and LSCM, in order to evaluate
      copper deposits in the peripheral cornea. RESULTS: No control subjects had
      corneal changes at both traditional biomicroscopy and LSCM. Only 25% of WD
      patients had detectable slit lamp changes, compared with 75% with LSCM
      examination. All cases detected by slit lamp were detected by LSCM. A significant
      correlation (p < 0.01) was found between deposit intensity at LSCM and daily
      urinary copper excretion. CONCLUSION: LSCM could detect copper deposition in WD
      corneas in more patients than traditional examination; it may therefore provide
      important information in cases of suspected WD diagnosis.

PMID- 24107715
TI  - Kruppel-like factor 2 regulates dendritic cell activation in patients with acute
      coronary syndrome.
AB  - OBJECTIVE: Dendritic cells (DCs) activation is important in atherosclerosis and
      coronary heart disease, but the mechanisms regulating activation of dendritic
      cells remain largely unclear. The aim of this study was to evaluate the effect of
      transcription factor Kruppel-like factor 2 (KLF2) in the proinflammatory
      activation of DCs in acute coronary syndrome. METHODS AND RESULTS: In this study,
      the expression of CD80 and KLF2 was detected in DCs in normal health controls,
      patients with stable angina (SA), and acute coronary syndrome (ACS). Our study
      found that compared with normal control and SA, KLF2 expression in DCs is reduced
      in patients with ACS. Moreover, the surface expression of CD80 was increased in
      ACS. In vitro experiment, we found that ox-LDL could increase CD80 expression and
      decrease KLF2 expression. Furthermore, down-regulated KLF2 could in turn increase
      CD80 expression via NF-kappaB pathway. CONCLUSIONS: These observations identify
      KLF2 as a novel negative regulator of DC function and it may play an essential
      role in DC activation in ACS.

PMID- 24107716
TI  - Ectopic adrenal rests in congenital adrenal hyperplasia as a cause of androgen
      excess after adrenalectomy detected by pelvic venous sampling.
AB  - BACKGROUND: Patients with classic congenital adrenal hyperplasia (CAH) due to
      CYP21 deficiency are treated with supraphysiological doses of glucocorticoids to
      suppress elevated androgen production. This implies also side effects of high
      dose glucocorticoids, possibly leading to iatrogenic Cushing's syndrome.
      Bilateral adrenalectomy has been suggested as the ultimate therapy in severe
      cases, when insufficient androgen suppression was obtained despite high
      glucocorticoid doses. Usually, ACTH levels rise after bilateral adrenalectomy,
      and this could imply an increased risk for the development of ectopic adrenal
      rests. In female CAH patients ovarian adrenal rests are not commonly detected by
      conventional radiological techniques. METHODS: We report the case of an adult
      female CAH patient who underwent bilateral adrenalectomy in early puberty because
      of poorly controlled CAH. RESULTS AND CONCLUSIONS: Several years after surgery,
      she developed secondary amenorrhea and hair loss as a result of androgen
      overproduction in ovarian adrenal rests that appeared to be detectable only by
      pelvic venous sampling. After unilateral oophorectomy androgen levels normalized.

PMID- 24107717
TI  - Renal failure in cirrhosis: is it time to change the diagnosis and
      classification?

PMID- 24107718
TI  - Factors associated with not using folic acid supplements preconceptionally.
AB  - OBJECTIVE: Neural tube defects are among the most common birth defects worldwide.
      Folic acid intake from one month before to three months after conception reduces
      the likelihood of neural tube defects by at least 50%. Since 1995, several
      campaigns have been organised in the Netherlands which resulted in 51% of
      pregnant women using folic acid supplements during the entire recommended period
      in the northern part of the Netherlands in 2005. Our research question was to
      gain insight into the current prevalence and factors associated with inadequate
      pregnancy-related use of folic acid supplements. DESIGN: Data from the DELIVER
      study were used, which is a population-based cohort study. SETTING: Twenty
      midwifery practices across the Netherlands in 2009 and 2010. SUBJECTS: In total
      5975 pregnant women completed a questionnaire covering items on sociodemographic
      and lifestyle factors, including folic acid intake. RESULTS: Of our study
      population, 55.5% (3318/5975) used folic acid supplements before conception.
      Several sociodemographic and lifestyle factors were associated with no
      preconception use of folic acid, of which non-Western ethnicity and not having a
      partner had the largest effect size. CONCLUSIONS: In the Netherlands, the folic
      acid intake before conception is suboptimal and has not improved over recent
      years. Fortification of staple foods with folic acid should be reconsidered as it
      would provide a more effective means of ensuring an adequate intake, especially
      for those groups of women who are unlikely to plan their pregnancies or to
      receive or respond to health promotion messages.

PMID- 24107719
TI  - Dollars and sense: the financial impact of Canadian wellness initiatives?.
AB  - The popular press reports anecdotal benefits of organizational initiatives that
      are designed to improve employees' work-life balance and wellness, but the long
      term impact of these initiatives on firms' financial performance is unknown. Our
      longitudinal study of publicly traded Canadian organizations uses the strategic
      human resources management framework to explain why these initiatives may affect
      their financial performance. We use an exploratory factor analysis of three waves
      of archival data to identify two types of initiatives and regression to measure
      their impact on return on assets (ROA). Our findings suggest that, after 2 years,
      health promotion initiatives significantly decreased ROA, while work-life balance
      initiatives significantly increased it. Both effects became non-significant over
      the longer term. 

PMID- 24107720
TI  - Acrylic resin injection method for blood vessel investigations.
AB  - The injection of acrylic resin into vessels is an excellent method for
      macroscopically and microscopically observing their three-dimensional features.
      Conventional methods can be enhanced by removal of the polymerization inhibitor
      (hydroquinone) without requiring distillation, a consistent viscosity of
      polymerized resin, and a constant injection pressure and speed. As microvascular
      corrosion cast specimens are influenced by viscosity, pressure, and speed
      changes, injection into different specimens yields varying results. We devised a
      method to reduce those problems. Sodium hydroxide was used to remove hydroquinone
      from commercial methylmethacrylate. The solid polymer and the liquid monomer were
      mixed using a 1 : 9 ratio (low-viscosity acrylic resin, 9.07 +/- 0.52 mPa*s) or a
      3:7 ratio (high-viscosity resin, 1036.33 +/- 144.02 mPa*s). To polymerize the
      acrylic resin for injection, a polymerization promoter (1.0% benzoyl peroxide)
      was mixed with a polymerization initiator (0.5%, N, N-dimethylaniline). The
      acrylic resins were injected using a precise syringe pump, with a 5-mL/min
      injection speed and 11.17 +/- 1.60 mPa injection pressure (low-viscosity resin)
      and a 1-mL/min injection speed and 58.50 +/- 5.75 mPa injection pressure (high
      viscosity resin). Using the aforementioned conditions, scanning electron
      microscopy indicated that sufficient resin could be injected into the capillaries
      of the microvascular corrosion cast specimens. 

PMID- 24107721
TI  - Immunohistochemical study on androgen receptors in the anterior cruciate ligament
      in dogs.
AB  - Androgen is closely involved as the cause of rupture of anterior cruciate
      ligament (ACL) in human. In dogs, however, factors contributing to rupture of ACL
      remain unknown. In this study, expression of androgen receptor (AR) and
      histological distribution of blood vessels in ACL, and serum testosterone
      concentration were investigated in relation with age and sex to confirm whether
      canine ACL is an androgen-responsive tissue. Materials of ACL were obtained from
      26 dogs: 12 young female Beagles, 2 old female mixed breeds, 9 young male
      Beagles, and 3 old male mixed breeds. In all canine ACL, positive AR expression
      was recognized in the nuclei of the fibrocytes, fibroblasts, synovial cells, and
      vascular endothelial cells of ACL. Expressions of AR were lesser in old males
      compared to the young males; however, females had no age difference in
      expression. Distributions of blood vessels in the synovial membrane of the
      ligament were fewer in old dogs both of males and females than youngs. Although
      distributions of vessels in the interstitium were apparently fewer in young
      females. Serum testosterone concentration was significantly higher in young
      males. Females had no age difference in the levels. From these results, it is
      suggested that canine ACL is an androgen-responsive tissue, and this
      consideration seems to closely relate to the epidemiological background that the
      incidence of rupture of ACL of dogs is higher in females than in males. 

PMID- 24107722
TI  - Effects of glucocorticoid on postnatal development of rat sublingual glands.
AB  - Hormones have been reported to be involved in salivary gland's growth and
      development, but few studies have investigated the effects of glucocorticoids on
      the morphology of the sublingual glands around the weaning period. The objective
      of this study was to ascertain the effects of glucocorticoid administration on
      rat sublingual glands around the weaning period. Male Wistar rats were
      administered triamcinolone, a glucocorticoid, once every other day from 8 days
      after birth (experimental group). A control group was given vehicle only. The
      sublingual glands were then extracted at 15, 20, 25, and 30 days after birth.
      Samples thus obtained were subjected to Alcian blue and periodic acid-Schiff
      staining, lectin staining, and immunohistochemical staining to assess cellular
      proliferative potential. And acinar cell circumferences were measured. We found
      that glucocorticoid had no effect on the production of acid or neutral
      mucopolysaccharides by acinar cells around the weaning period. Glucocorticoid
      administration resulted in hypertrophy of acinar cells between 15 and 30 days
      after birth. Early appearance of changes in alpha-mannose, alpha-glucosamine, and
      N-acetylglucosamine in secretory granules suggested that glucocorticoid may have
      acted to promote cell differentiation. The glucocorticoid had no effect on the
      proliferative potential of sublingual gland acinar cells around the weaning
      period. 

PMID- 24107723
TI  - Guidelines, organ damage, diagnostic procedures and treatment.

PMID- 24107724
TI  - 2013 Practice guidelines for the management of arterial hypertension of the
      European Society of Hypertension (ESH) and the European Society of Cardiology
      (ESC): ESH/ESC Task Force for the Management of Arterial Hypertension.

PMID- 24107725
TI  - Immune mechanisms in hypertension: how do T-regulatory lymphocytes fit in?

PMID- 24107726
TI  - Blood pressure and retinal small arteries.

PMID- 24107727
TI  - Can we use mineralocorticoid receptor blockade in diabetic patients with
      resistant hypertension? Yes we can! But it may be a double-edged sword.

PMID- 24107728
TI  - Family history as a predictor of hospitalization for hypertension in Sweden.
AB  - OBJECTIVE: Hypertension clusters in families. However, no nationwide study has
      investigated the family history as a predictor of hospitalization for
      hypertension, which was the purpose of this study. RESEARCH DESIGN AND METHODS:
      The study is a nationwide follow-up study. Swedish Multigeneration Register data
      for individuals aged 0-76 years were linked to Hospital Discharge Register data
      for 1964-2008. Standardized incidence ratios (SIRs) were calculated for
      individuals whose relatives were hospitalized with a main diagnosis of
      hypertension compared with those whose relatives were not. RESULTS: The total
      number of patients hospitalized with hypertension was 37,686. The familial SIR
      was 2.18 for individuals with one affected sibling, 44.83 for individuals with
      two affected siblings and 57.18 for individuals with three or more affected
      siblings. The SIR was 1.95 for parents with one affected child, 3.73 for parents
      with two affected children and 9.22 for parents with three or more affected
      children. The familial SIR among offspring was 1.84 for those with one affected
      parent and 3.62 for those with two affected parents. The familial risk for
      hospitalization with hypertension among offspring aged less than 30 years was
      2.50 and 1.57 in those aged more than 60 years. Familial risks were similar for
      men and women. Spouses had low overall familial risks (SIR=1.2). CONCLUSION:
      Hospitalization for hypertension clusters in families. Very high risks were
      observed in families with multiple affected siblings, though the parent-offspring
      transmission was lower, suggesting the segregation of recessive or interacting
      susceptibility genes. The low familial risk in spouses suggests a minor
      nongenetic contribution.

PMID- 24107729
TI  - Adrenomedullin is a marker of carotid plaques and intima-media thickness as well
      as brachial pulse pressure.
AB  - BACKGROUND: Adrenomodulin (ADM) is a peptide hormone secreted in response to
      cellular strain such as ischemia and is believed to have a beneficial effect on
      the cardiovascular system. However, the epidemiological relationships between ADM
      and measurements of haemodynamics, arteriosclerosis and atherosclerosis are not
      well established. The aim of this study was to investigate the association
      between the mid-regional part of pro-ADM (MR-proADM) and brachial pulse pressure
      (PP), carotid intima-media thickness (cIMT) and carotid atherosclerosis. METHOD:
      This study has a cross-sectional design and includes 4924 individuals (mean age
      58 years, 40% men) from Malmo, Sweden, examined between 1991 and 1994.
      Participants underwent physical examination, measurement of MR-proADM and
      ultrasound of the carotid arteries. RESULTS: There was a positive association
      between MR-proADM and brachial PP, cIMT as well as a carotid plaque score. The
      associations were significant after adjustment for age, sex, BMI, hypertension,
      diabetes, low-density lipoprotein cholesterol and smoking. CONCLUSION: ADM is
      positively associated with brachial PP and both carotid IMT and plaques,
      suggesting a role for ADM in early haemodynamic pathophysiology related to
      arteriosclerosis and the atherosclerotic plaque development.

PMID- 24107730
TI  - Salt intake in children 10-12 years old and its modification by active working
      practices in a school garden.
AB  - OBJECTIVE: The aim of the study was to evaluate the 24-h urinary sodium excretion
      in children of 10-12 years at a school in the north of Portugal and to examine
      the influence on salt intake and blood pressure of three different educational
      interventions for 6 months. METHODS: Blood pressure (BP) and sodium excretion in
      24-h urinary samples (UNa) validated with urinary creatinine were measured in 155
      children 10-12 years old belonging to nine classes at baseline and after 6 months
      of three educational interventions in students from three classes each after
      parents consent was obtained. Interventions consisted in no additional action
      [control (CTR)], weekly lessons about the dangers of high salt intake
      [Theoretical (THEOR)] and both lessons and working practices in the school garden
      of planting, collection of herbs for salt substitution at home [practical
      (PRACT)]. RESULTS: At baseline 139 students (76 girls and 63 boys) were eligible
      showing average 24-h UNa of 132+/-43 mmol/24 h (mean salt intake of 7.8+/-2.5 g
      per day) and BP of 118/62 (13/9) mmHg that did not correlate to each other. At
      the end of the study, versus baseline, BP decreased by 8.2/6.5 mmHg in CTR
      (n=31), by 3.8/0.6 mmHg in THEOR (n=43) and by 3.5/0.7 mmHg in PRACT (n=53) and
      salt intake was reduced by 0.4+/-2.4 g per day in CTR, by 0.6+/-3.2 g per day in
      THEOR and by 1.1+/-2.5 g per day in PRACT. It was observed that salt intake
      variation was not independent of the group (CRT, THEOR and PRACT) (chi, 9.982,
      P=0.041). Salt intake was significantly reduced only in the PRACT group (1.1 g
      per day) and in the PRACT group the percentage of children who reduced salt
      intake by at least 1g per day from baseline to the end of the study was
      significantly higher (50.9%) than that of the other groups, THEOR, 48.8% and CTR,
      32.2%. CONCLUSION: Our data indicates that children 10-12 years old have a high
      salt intake that is well above the proposed recommendations and that a strategy
      based on theoretical and practical education may achieve in some children an
      important reduction in daily salt intake which, if maintained over time, may
      assume important public health implications. These results suggest that in those
      children a more complete theoretical and practical intervention is more
      productive and efficient towards reduction of salt intake than single theoretical
      or no intervention.

PMID- 24107731
TI  - Arterial stiffness is increased in asymptomatic nondiabetic postmenopausal women
      with a polycystic ovary syndrome phenotype.
AB  - OBJECTIVE: The metabolic dysfunction accompanying the polycystic ovary syndrome
      (PCOS) may increase the risk of hypertension and cardiovascular disease (CVD).
      Although menopause per se may be an additional risk factor of CVD, the
      association between PCOS in postmenopausal women and cardiovascular risk has not
      been adequately investigated. We aimed to evaluate the effect of PCOS on markers
      of subclinical atherosclerosis in nondiabetic postmenopausal women. METHODS: This
      cross-sectional study included 286 postmenopausal women with intact ovaries. PCOS
      phenotype was defined if three of the following were present: insulin resistance,
      current hyperandrogenism or history of clinical androgen excess, history of
      infertility, central obesity and history of irregular menses. Traditional CVD
      risk factors, as well as indices of arterial structure (intima-media thickness,
      atheromatous plaques presence) and function [flow-mediated dilation, pulse wave
      velocity (PWV), augmentation index] were compared between women with a PCOS
      phenotype and the rest of the sample, who served as controls. RESULTS: Women with
      the PCOS phenotype (N=43) had higher SBP and triglycerides and lower high-density
      lipoprotein (HDL)-cholesterol than controls. Mean values of PWV differed
      significantly between PCOS cases and controls (9.46+/-1.74 vs. 8.60+/-1.51 m/s,
      P=0.001, univariate). Multivariate regression analysis showed that the PCOS
      phenotype, age and SBP were the only independent predictors of PWV. CONCLUSION:
      Arterial stiffness is increased in asymptomatic, nondiabetic women with a
      putative PCOS phenotype, independently of age, BMI or blood pressure. This might
      present one mechanism through which PCOS increases the risk of CVD and
      hypertension later in life.

PMID- 24107732
TI  - Repeating adrenal vein sampling when neither aldosterone/cortisol ratio exceeds
      peripheral yields a high incidence of aldosterone-producing adenoma.
AB  - OBJECTIVES: In primary aldosteronism, adrenal vein sampling (AVS) suggests
      unilateral aldosterone-producing adenoma (APA) when the aldosterone/cortisol
      (A/F) ratio is less than or equal to peripheral on one side and at least two
      times peripheral on the other. When A/F ratios are lower bilaterally than
      peripheral despite adequate samples (adrenal venous cortisol >=3 times
      peripheral), we recommend repeat AVS. This study aimed to determine the frequency
      of this occurrence and outcomes in such cases. METHODS: We performed a
      retrospective observational study of all cases of primary aldosteronism
      undergoing initial AVS over a 34-year period. RESULTS: Initial AVS in 1397
      patients returned satisfactory and discriminatory results in 1066 (76.3%) but 37
      patients (2.6%) had adequate samples but bilateral A/F ratios no higher than
      peripheral. Of the 22 of these 37 who agreed to repeat AVS, 10 demonstrated
      unilateral aldosterone production, and eight of these had unilateral
      adrenalectomy disclosing APAs and resulting in cure (3) or improvement (5) in
      hypertension. Eight had bilateral aldosterone production. Four studies were
      inconclusive. Patients with initial unsatisfactory AVS because of bilaterally low
      A/F ratios had significantly (P=0.023) more unilateral disease [10 of 18
      satisfactory repeat studies (55.6%) vs. 326 of 1066 satisfactory initial studies
      (30.6%)] and a significantly higher (67.6 vs. 49.9%, P=0.034) percentage of
      males. CONCLUSION: As the incidence of APAs was high in a subgroup with low A/F
      bilaterally on initial AVS, these patients should be offered repeat AVS. This
      might reflect both a greater dependence of aldosterone production on
      adrenocorticotrophic hormone (ACTH) in APAs and the pulsatile nature of ACTH
      secretion.

PMID- 24107733
TI  - Ca2+ sensitization and Ca2+ entry in the control of blood pressure and adrenergic
      vasoconstriction in conscious Wistar-Kyoto and spontaneously hypertensive rats.
AB  - BACKGROUND: Calcium entry through nifedipine-sensitive L-type voltage-dependent
      calcium channels (L-VDCC) is augmented in spontaneously hypertensive rats (SHR)
      characterized by enhanced sympathetic vasoconstriction. However, the changes of
      calcium sensitization mediated by RhoA/Rho kinase pathway are less understood.
      METHODS AND RESULTS: The participation of calcium entry and calcium sensitization
      in the control of blood pressure (BP) and vascular contraction was studied in SHR
      and normotensive Wistar-Kyoto (WKY) rats. The acute administration of fasudil
      (Rho kinase inhibitor) caused BP decrease which lasted longer in SHR. Fasudil
      also attenuated adrenergic contraction in femoral or mesenteric arteries of WKY
      and SHR. BP reduction elicited by fasudil in WKY was more pronounced than that
      induced by L-VDCC blocker nifedipine (-33+/-2 vs. -15+/-3% of baseline BP,
      P<0.001), whereas both inhibitors were similarly effective in SHR (-36+/-4 vs. 
      41+/-2%). Fasudil pretreatment also attenuated BP elevation elicited by L-VDCC
      agonist BAY K8644 more in WKY than in SHR (-63+/-4 vs. -42+/-5%, P<0.001),
      indicating reduced calcium sensitization in SHR. Moreover, fasudil pretreatment
      shifted norepinephrine dose-response curves to the right more in WKY than in SHR.
      The additional nifedipine pretreatment shifted these curves further to the right
      but this shift was more pronounced in SHR than in WKY. Thus adrenergic
      vasoconstriction is more dependent on L-VDCC in SHR and on RhoA/Rho kinase
      pathway in WKY rats. CONCLUSION: Ca sensitization mediated by RhoA/Rho kinase
      pathway is attenuated in SHR compared with normotensive WKY rats. This might be a
      part of the compensation for enhanced Ca entry through L-VDCC in genetic
      hypertension.

PMID- 24107734
TI  - Hypertensive renal disease: susceptibility and resistance in inbred hypertensive
      rat lines.
AB  - BACKGROUND: Spontaneously hypertensive rat (SHR) lines differ in their
      susceptibility to hypertensive end-organ disease and may provide an informative
      model of genetic risk of disease. Lines derived from the original SHR-B and SHR-C
      clades are highly resistant to hypertensive end-organ disease, whereas lines
      derived from the SHR-A clade were selected for stroke susceptibility and
      experience hypertensive renal disease. METHOD: Here we characterize the temporal
      development of progressive renal injury in SHR-A3 animals consuming 0.3% sodium
      in the diet and drinking water. SHR-A3 rats demonstrate albuminuria, glomerular
      damage, tubulointerstitial injury, and renal fibrosis that emerge at 18 weeks of
      age and progress. RESULTS AND CONCLUSION: Mortality of SHR-A3 animals was 50% at
      40 weeks of age, and animals surviving to this age had reduced renal function. In
      contrast SHR-B2, which are 87% genetically identical to SHR-A3, are substantially
      protected from renal injury and demonstrate only moderate changes in albuminuria
      and renal histological injury over this time period. At 40 weeks of age, electron
      microscopy of the renal glomerulus revealed severe podocyte effacement in SHR-A3,
      but slit diaphragm architecture in SHR-B2 at this age was well preserved. Renal
      injury traits in the F1 and F2 progeny of an intercross between SHR-A3 and SHR-B2
      were measured to determine heritability of renal injury in this model.
      Heritability of albuminuria, glomerular injury, and tubulointerstitial injury
      were estimated at 48.9, 66.5 and 58.6%, respectively. We assessed the
      relationship between blood pressure and renal injury measures in the F2 animals
      and found some correlation between these variables that explain up to 26% of the
      trait variation. Quantitative trait locus (QTL) mapping was performed using over
      200 single nucleotide polymorphism markers distributed across the 13% of the
      genome that differs between these two closely related lines. Mapping of
      albuminuria, tubulointerstitial injury, and renal fibrosis failed to identify
      loci linked with disease susceptibility, suggesting a complex inheritance of
      disease risk. We detected a single QTL conferring susceptibility to glomerular
      injury that was confined to a small haplotype block at chromosome 14:70-76Mb.

PMID- 24107735
TI  - Geometry-independent inclusion of basal myocardium yields improved cardiac
      magnetic resonance agreement with echocardiography and necropsy quantified left
      ventricular mass.
AB  - OBJECTIVES: Left-ventricular mass (LVM) is widely used to guide clinical decision
      making. Cardiac magnetic resonance (CMR) quantifies LVM by planimetry of
      contiguous short-axis images, an approach dependent on reader-selection of images
      to be contoured. Established methods have applied different binary cut-offs using
      circumferential extent of left-ventricular myocardium to define the basal left
      ventricle (LV), omitting images containing lesser fractions of left-ventricular
      myocardium. This study tested impact of basal slice variability on LVM
      quantification. METHODS: CMR was performed in patients and laboratory animals.
      LVM was quantified with full inclusion of left-ventricular myocardium, and by
      established methods that use different cut-offs to define the left-ventricular
      basal-most slice: 50% circumferential myocardium at end diastole alone (ED50),
      50% circumferential myocardium throughout both end diastole and end systole
      (EDS50). RESULTS: One hundred and fifty patients and 10 lab animals were studied.
      Among patients, fully inclusive LVM (172.6+/-42.3g) was higher vs. ED50 (167.2+/
      41.8g) and EDS50 (150.6+/-41.1g; both P<0.001). Methodological differences
      yielded discrepancies regarding proportion of patients meeting established
      criteria for left-ventricular hypertrophy and chamber dilation (P<0.05). Fully
      inclusive LVM yielded smaller differences with echocardiography (Delta=11.0+/
      28.8g) than did ED50 (Delta=16.4+/-29.1g) and EDS50 (Delta=33.2+/-28.7g; both
      P<0.001). Among lab animals, ex-vivo left-ventricular weight (69.8+/-13.2g) was
      similar to LVM calculated using fully inclusive (70.1+/-13.5g, P=0.67) and ED50
      (69.4+/-13.9g; P=0.70) methods, whereas EDS50 differed significantly (67.9+/
      14.9g; P=0.04). CONCLUSION: Established CMR methods that discordantly define the
      basal-most LV produce significant differences in calculated LVM. Fully inclusive
      quantification, rather than binary cut-offs that omit basal left-ventricular
      myocardium, yields smallest CMR discrepancy with echocardiography-measured LVM
      and non-significant differences with necropsy-measured left-ventricular weight.

PMID- 24107736
TI  - Association of a prothrombotic state with left-ventricular diastolic dysfunction
      in hypertension: a tissue-Doppler imaging study.
AB  - OBJECTIVES: In hypertensive patients the propensity to develop organ damage is
      under the influence of several factors, including the existence of a
      prothrombotic state. We tested the hypothesis that an activated hemostatic system
      is associated with left-ventricular diastolic dysfunction as assessed by tissue
      Doppler imaging (TDI). METHODS: In 198 patients with untreated essential
      hypertension free of clinically relevant cardiovascular complications, we
      measured plasma levels of fibrinogen, prothrombin fragment 1 + 2, D-dimer,
      plasminogen activator inhibitor-1, and tissue plasminogen activator, and
      performed conventional echocardiography and TDI. RESULTS: Left-ventricular
      diastolic dysfunction was detected in 61 patients (31%) by conventional
      echocardiography and in 105 patients (53%) by TDI, 39% of whom had left
      ventricular hypertrophy. Left-ventricular hypertrophy was associated with
      increased plasma fibrinogen and prothrombin fragment 1 + 2 levels. Patients with
      diastolic dysfunction at TDI were older and had greater BMI, SBP, left
      ventricular mass index, and plasma fibrinogen and D-dimer levels than patients
      with normal diastolic function. Variables of diastolic function measured both at
      conventional echocardiography and TDI were significantly related with age, BMI,
      left-ventricular mass index, and plasma fibrinogen, D-dimer, and prothrombin
      fragment 1 + 2. Multivariate regression analysis showed that diastolic variables
      obtained at TDI were related to plasma fibrinogen levels independent of
      covariates. CONCLUSION: Elevated plasma levels of fibrinogen and a prothrombotic
      state are associated with the presence of left-ventricular diastolic dysfunction
      in hypertensive patients with no evidence of ischemic heart disease and might
      increase the risk of diastolic heart failure.

PMID- 24107737
TI  - Aldosterone synthase inhibition for the treatment of hypertension and the derived
      mechanistic requirements for a new therapeutic strategy.
AB  - CONTEXT: We describe the clinical investigation of the first generation
      aldosterone synthase inhibitor, LCI699, in patients with essential, uncontrolled,
      resistant, or secondary hypertension. LCI699 competitively reduced blood pressure
      at lower doses yet counterintuitive effects were observed at higher doses.
      OBJECTIVE AND METHOD: An extensive endocrine biomarker analysis was performed to
      better understand the pharmacological mechanism of the drug. RESULTS: The
      interference of LCI699 in the renin-angiotensin-aldosterone system occurred with
      limited target selectivity, as a dose-dependent compensatory stimulation of the
      hypothalamic-pituitary-adrenal feedback axis was discovered. Thus, LCI699
      affected two endocrine feedback loops that converged at a single point,
      inhibiting the 11beta-hydroxylase reaction in the adrenal gland, leading to
      supraphysiological levels of 11-deoxycortiscosterone. The accumulation of this
      potent mineralocorticoid may explain the blunted blood pressure response to
      LCI699. CONCLUSION: Future aldosterone synthase inhibitors may improve their
      target selectivity by sparing the 11beta-hydroxylase reaction and preferentially
      inhibiting one of the two other enzymatic reactions mediated by aldosterone
      synthase.

PMID- 24107738
TI  - Low dose spironolactone reduces blood pressure in patients with resistant
      hypertension and type 2 diabetes mellitus: a double blind randomized clinical
      trial.
AB  - BACKGROUND: The increased risk of cardiovascular morbidity and mortality
      associated with arterial hypertension is particularly pronounced in patients with
      type 2 diabetes mellitus. Blood pressure control is, therefore, decisively
      important but often not sufficiently achieved. OBJECTIVE: The primary objective
      of this study was to evaluate the antihypertensive effect of low dose
      spironolactone added to triple therapy for resistant hypertension in patients
      with type 2 diabetes measured by ambulatory monitoring. Secondary objectives were
      to evaluate the effects on glycaemic control and urinary albumin excretion as
      well as adverse effects. METHODS: In a multicentre, double-blind, randomized,
      placebo-controlled study 119 patients with blood pressure at or above 130/80 mmHg
      despite triple antihypertensive therapy were included. One tablet of 25 mg
      spironolactone or placebo was added to previous treatment and increased to two if
      blood pressure below 130/80 mmHg was not achieved after 4 weeks. Blood pressure
      was measured by ambulatory monitoring at baseline and after 16 weeks. RESULTS:
      The study was completed by 112 patients, 57 randomized to spironolactone and 55
      to placebo. Average daytime placebo-corrected blood pressure was reduced by 8.9
      (4.7-13.2)/3.7 (1.5-5.8) mmHg. Also office blood pressure, night-time, 24-h and
      pulse pressures were reduced significantly. Urinary albumin/creatinine ratio was
      significantly reduced in the spironolactone group. Glycaemic control remained
      unchanged. Hyperkalemia was the most frequent adverse event leading to dose
      reduction in three cases and discontinuation in one, whereas gynaecomastia was
      not reported. CONCLUSION: Low dose spironolactone exerts significant BP and
      urinary albumin creatinine ratio lowering effects in high-risk patients with
      resistant hypertension and type 2 diabetes mellitus.

PMID- 24107739
TI  - Platelet activation during exercise is not attenuated by inhibition of the renin
      angiotensin system: the role of physical activity.

PMID- 24107740
TI  - Platelet activation during exercise is not attenuated by inhibition of the renin
      angiotensin system: the role of physical activity.

PMID- 24107741
TI  - Emergence and persistence of overweight and obesity in 7- to 11-year-old
      children.
AB  - AIM: After dramatic rises in paediatric obesity, the critical period for obesity
      onset may now be pre-adolescence. METHODS: We monitored adiposity over 4 years in
      400 children aged 7-9 years recruited from schools in London. Weight, height,
      waist circumference (WC) and fat mass were measured annually. Weight status was
      defined using International Obesity Task Force (IOTF) criteria, and standardised
      scores and percentiles used British 1990 reference data. RESULTS: BMI, WC and fat
      mass index all tracked strongly over time (average correlation for BMI = 0.95).
      Emergence of obesity was relatively uncommon: only 2% of the total sample
      increased from overweight to obese over the 4-year period, and this was nearly
      matched by the 1.3% that reduced from obese to overweight. However, more children
      (6%) moved from healthy weight to overweight than the reverse direction (2%).
      There were greater absolute gains in adiposity in children with higher baseline
      weight status, but this was disguised in analyses using standardised scores.
      Obesity was not an emergent trait in middle childhood, but rates were already
      high and, in absolute terms, adiposity increased more in overweight and obese
      than healthy weight children. CONCLUSION: These results highlight the need for
      active management of obesity in middle childhood.

PMID- 24107743
TI  - Self-efficacy partially mediates between social support and health-related
      quality of life in family caregivers for dementia patients in Shanghai.
AB  - BACKGROUND: There is a paucity of research assessing health-related quality of
      life (HRQoL) and self-efficacy in caregivers of relatives with dementia in
      mainland China. AIMS: To compare the level of HRQoL between caregivers and the
      general population in mainland China and to assess the role of caregiver self
      efficacy in the relationship between caregiver social support and HRQoL. METHODS:
      A cross-sectional study was conducted in Shanghai, China. The caregivers were
      recruited from the outpatient department of a teaching hospital. A total of 195
      participants were interviewed, using a survey package including the Chinese
      version of the 36-Item Short-Form Health Survey (SF-36), demographic data, the
      variables associated with the impairments of care recipients, perceived social
      support and caregiver self-efficacy. The caregivers' SF-36 scores were compared
      with those of the general population in China. RESULTS: The results indicated
      that the HRQoL of the caregivers was poorer compared with that of the general
      population when matched for age and gender. Multiple regression analyses revealed
      that caregiver self-efficacy is a partial mediator between social support and
      HRQoL, and a partial mediator between behavioral and psychological symptoms of
      dementia (BPSD) and caregiver mental health. CONCLUSION: Assisting with managing
      BPSD and enhancing caregiver self-efficacy can be considered integral parts of
      interventions to improve caregiver HRQoL.

PMID- 24107742
TI  - Effects of full-length kisspeptin administration on follicular development in
      Japanese Black beef cows.
AB  - Kisspeptin is a key molecule that stimulates gonadotropin secretion via release
      of gonadotropin-releasing hormone (GnRH). In the present study, our aim was to
      investigate whether kisspeptin has stimulatory effects on follicular development
      via GnRH/gonadotropin secretion in cows. Japanese Black beef cows were
      intravenously injected with full-length bovine kisspeptin [Kp-53 (0.2 or 2
      nmol/kg)] or vehicle 5 days after they exhibited standing estrus (Day 0). In cows
      injected with Kp-53 at 2 nmol/kg, the follicular sizes of the first dominant
      follicles increased on Day 6 and thereafter. Ovulation of the first dominant
      follicle occurred in 1 out of 4 cows treated with Kp-53 at 2 nmol/kg. Injection
      of Kp-53 at 2 nmol/kg increased the concentration of plasma luteinizing hormone
      (LH) but not follicle-stimulating hormone, over a 4-h period following injection
      in all cows. The present study suggests that administration of full-length
      kisspeptin causes LH secretion, which is sustained for a few hours, and it is
      capable of stimulating follicular development and/or ovulation. 

PMID- 24107745
TI  - Total inward leakage measurement of particulates for N95 filtering facepiece
      respirators--a comparison study.
AB  - National Institute for Occupational Safety and Health (NIOSH) certified
      particulate respirators need to be properly fit tested before use to ensure
      workers' respiratory protection. However, the effectiveness of American National
      Standards Institute-/Occupational Safety and Health Administration (ANSI-/OSHA)
      accepted fit tests for particulate respirators in predicting actual workplace
      protection provided to workers is lacking. NIOSH addressed this issue by
      evaluating the fit of half-mask particulate filtering respirators as a component
      of a program designed to add total inward leakage (TIL) requirements for all
      respirators to Title 42 Code of Federal Regulations Part 84. Specifically, NIOSH
      undertook a validation study to evaluate the reproducibility of the TIL test
      procedure between two laboratories. A PortaCount(r) was used to measure the TIL
      of five N95 model filtering facepiece respirators (FFRs) on test subjects in two
      different laboratories. Concurrently, filter efficiency for four of the five N95
      FFR models was measured using laboratory aerosol as well as polydisperse NaCl
      aerosol employed for NIOSH particulate respirator certification. Results showed
      that two N95 models passed the TIL tests at a rate of ~80-85% and ~86-94% in the
      two laboratories, respectively. However, the TIL passing rate for the other three
      N95 models was 0-5.7% in both laboratories combined. Good agreement (>=83%) of
      the TIL data between the two laboratories was obtained. The three models that had
      relatively lower filter efficiency for laboratory aerosol as well as for NaCl
      aerosol showed relatively low TIL passing rates in both laboratories. Of the four
      models tested for penetration, one model with relatively higher efficiency showed
      a higher passing rate for TIL tests in both laboratories indicating that filter
      efficiency might influence TIL. Further studies are needed to better understand
      the implications of the data in the workplace. 

PMID- 24107746
TI  - Cutaneous reactive angiomatosis with combined histological pattern mimicking a
      cellulitis.
AB  - Cutaneous reactive angiomatoses (CRA) encompass a distinct group of rare benign
      reactive vascular proliferations that include reactive angioendotheliomatosis,
      diffuse dermal angiomatosis and reactive intralymphatic histiocytosis. The
      etiology of these conditions, often associated with either localized or systemic
      diseases, is poorly understood. We report a 72-year-old woman who presented giant
      diffuse cellulitis-like plaques on the right lower limb and the pelvis and a
      reduction of her general condition with fever. Light microscopy studies revealed
      combined features of reactive angioendotheliomatosis, diffuse dermal angiomatosis
      and reactive intralymphatic histiocytosis. A small arteriovenous fistula of the
      right lower leg was thought to act as trigger. Systemic corticosteroids resulted
      in the clinical remission of the skin lesions. Our observation provides strong
      evidence that reactive angioendotheliomatosis, diffuse dermal angiomatosis and
      reactive intralymphatic histiocytosis, previously regarded as distinct forms of
      CRA, may show overlapping histopathological features and most likely represent
      facets of the same disease.

PMID- 24107747
TI  - NACNS newsletter: president's message.

PMID- 24107748
TI  - The clinical nurse specialist role: perspectives of an administrator.

PMID- 24107749
TI  - A sociotechnical approach to successful electronic health record implementation:
      five best practices for clinical nurse specialists.
AB  - Rising healthcare costs coupled with patient safety considerations and quality of
      care have become major concerns for healthcare purchasers, providers, and
      policymakers. Health information technology, particularly the electronic health
      record (EHR), is posed as a solution to address these concerns by delivering
      greater efficiencies and improved quality of care. Despite the national movement
      toward EHR adoption, successful EHR implementation continues to be challenging
      for many healthcare organizations, both large and small. This article uses
      sociotechnical systems theory as a framework to discuss 5 best practice
      guidelines for EHR implementation and outlines what clinical nurse specialists
      can do to make the process successful. 

PMID- 24107750
TI  - Medication adherence and patient outcomes: part 2: interventions and resources to
      overcome low health literacy.
AB  - This article explores the influence of health literacy on medication adherence.
      With health literacy skills nearly flat for over a decade and an aging population
      receiving multiple and complex medication regimens, literacy is becoming a more
      important factor in nursing assessment and intervention. Concrete tools are
      provided to help the clinical nurse specialist (CNS) assess literacy and evaluate
      written resources for patient education and to improve medication adherence. 

PMID- 24107752
TI  - Perceptions of teamwork among code team members.
AB  - BACKGROUND: Cardiopulmonary arrest (CPA) teams, known as code teams, provide
      coordinated and evidenced-based interventions by various disciplines during a
      CPA. Teamwork behaviors are essential during CPA resuscitation and may have an
      impact on patient outcomes. OBJECTIVES: The purpose of this study was to explore
      the perceptions of teamwork during CPA events among code team members and to
      determine if differences in perception existed between disciplines within the
      code team. METHODS: A prospective, descriptive, comparative design using the Code
      Teamwork Perception Tool online survey was used to assess the perception of
      teamwork during CPA events by medical residents, critical care nurses, and
      respiratory therapists. RESULTS: Sixty-six code team members completed the Code
      Teamwork Perception Tool. Mean teamwork scores were 2.63 on a 5-point scale (0
      4). No significant differences were found in mean scores among disciplines.
      Significant differences among scores were found on 7 items related to code
      leadership, roles and responsibilities between disciplines, and in those who had
      participated on a code team for less than 2 years and certified in Advanced
      Cardiac Life Support for less than 4 years. CONCLUSIONS: Teamwork perception
      among members of the code team was average. Teamwork training for resuscitation
      with all disciplines on the code team may promote more effective teamwork during
      actual CPA events. Clinical nurse specialists can aid in resuscitation efforts by
      actively participating on committees, identifying opportunities for improvement,
      being content experts, leading the development of team training programs, and
      conducting research in areas lacking evidence.

PMID- 24107751
TI  - Black cohosh (Cimicifuga species) for menopausal symptoms.

PMID- 24107753
TI  - Dementia caregivers' lived experience of sleep.
AB  - PURPOSE: Poor sleep quality leads to sleep deficiency, an unmet public health
      problem that is especially acute in caregivers. The purpose of this study was to
      investigate the dementia caregiver's lived experience of sleep. The specific
      objectives were to (1) explore causes for poor sleep as identified by the
      caregiver, (2) gain knowledge about how the caregiver manages the sleep
      experience, and (3) gain an understanding of how caregivers perceive health
      promotion suggestions to improve sleep quality. METHODS: This was a qualitative
      study using a phenomenological framework. In 3 focus groups, data were collected
      from 15 informal/family member caregivers of a person with dementia (PWD).
      RESULTS: Three themes were identified in caregivers' descriptions of disruptions
      to their sleep quality: sleep quality fluctuating with the status of the PWD, a
      need for vigilance to safeguard the PWD at night, and worry about current and
      future events, which caused rumination. Caregivers did not receive formal help
      from healthcare providers but did participate in activities that promote good
      sleep. Caregivers identified barriers to health promotion activities, including
      lack of time, decreased energy, and additional costs for providing care for the
      PWD. CONCLUSION: This research provides exemplars of caregivers' thoughts,
      preferences, values, and beliefs regarding their sleep experience in the context
      of caregiving. The caregiver's perspective should be taken into consideration
      when clinical nurse specialists provide evidence-based care. Clinical
      implications are provided.

PMID- 24107754
TI  - Research involving participants with chronic diseases: overcoming recruitment
      obstacles.
AB  - Chronic diseases are rampant in the United States and account for the majority of
      healthcare costs in this country. The implementation of research studies
      involving members of chronic disease populations is necessary to the development
      of interventions aimed at preventing these conditions and improving outcomes. The
      implementation of such studies hinges on the successful recruitment of an
      adequate number of study participants. Difficulties surrounding participant
      recruitment in behavioral studies are well documented and present a barrier to
      researchers aiming to conduct research involving persons with chronic diseases.
      Common recruitment challenges associated with recruiting chronic disease
      participants are reviewed, and a highly effective, alternative recruitment
      strategy used by the authors in a qualitative study involving persons with
      epilepsy is discussed in detail. 

PMID- 24107755
TI  - Most frequently observed risk factors for adult inpatient injurious falls in
      hospitals.
AB  - PURPOSE: This exploratory, multihospital, cross-sectional nurse survey identified
      the adult population group with the most frequently observed risk factors for
      injurious falls in acute hospital settings. METHODOLOGY: The survey was conducted
      at 5 nonprofit health systems in the United States. A subset of the survey data
      from the main study was used in this analysis. The main study was conducted in
      2011-2012 and included 560 registered nurses (RNs) from 68 units; it was
      published in the Journal of Nursing Care Quality in 2013. All the subjects from
      the main study were included in the present study. Factor analysis was conducted
      on 81 risk factor frequency items. We identified the group based on the ranking
      of the mean values for the frequency groups. The risk factor effective
      preventability items were also analyzed. RESULTS: We identified 24 most
      frequently observed risk factors and 3 most effectively preventable risk factors,
      which were all integral to each individual patient. Five of the most frequently
      observed risk factors were identified as physical-motor factors, 8 were
      identified as cognition factors, and 4 were demographic characteristics. None of
      the most frequently observed risk factors were related to medication. The 3 most
      preventable risk factors were demographic characteristics. For exploratory
      purposes, 1-way analysis of variance tests were used and show that statistically
      significant differences were present in the mean scores on some of the frequency
      scales and effective preventability scales across study health systems, acuity
      levels of the units, and unit types. CONCLUSION/APPLICATION OF THE STUDY:
      Perceptions of RNs about the most frequently observed and the most effectively
      preventable risk factors were mostly inconsistent. Clinical nurse specialists and
      nursing administrators need to identify frequently observed risk factors on a
      regular basis. These findings need to be communicated with RN staff in a
      systematic way to prioritize interventions to prevent injurious falls.

PMID- 24107756
TI  - New graduate survey: factors that influence new nurses' selection of first
      clinical position.
AB  - AIM: The aim was to survey nurses with 2 to 3 years' experience to determine what
      factors were involved in the choice of their first nursing position and if they
      were still in that position. BACKGROUND: A false sense that the nursing shortage
      has ended has occurred with nurses delaying retirement until the economy
      improves. However, the turnover rate still shows 26% of registered nurses leaving
      their first hospital position within 2 years. METHODS: New graduate nurses were
      surveyed to determine if nursing was what they expected, what led them to their
      first position, if they were still in their first position, and factors that may
      have influenced these decisions. The 159 respondents also commented on their
      intent to stay and gave free-text responses. RESULTS: Significant difference was
      found between the current unit worked with both the unit wanted while in nursing
      school and the unit wanted upon graduation. Positive and negative narrative
      comments shed light on factors influencing intent to stay. CONCLUSION: Nurses are
      concerned with ability to deliver safe care, supportive management, and teamwork.
      IMPLICATIONS FOR NURSING MANAGEMENT: Recommendations were made for nursing
      management in creating an environment of continued learning and teamwork to
      support new graduate nurses.

PMID- 24107758
TI  - Lianna Z. Ansryan. Interview by Jo Ellen Rust.

PMID- 24107757
TI  - Graduate nursing education in the 21st century: there's an app for that!

PMID- 24107759
TI  - Shared mind: David Clegg's Trebus Project.

PMID- 24107761
TI  - Distinguishing bipolar II depression from major depressive disorder with comorbid
      borderline personality disorder: demographic, clinical, and family history
      differences.
AB  - OBJECTIVE: Because of the potential treatment implications, it is clinically
      important to distinguish between bipolar II depression and major depressive
      disorder with comorbid borderline personality disorder. The high frequency of
      diagnostic co-occurrence and resemblance of phenomenological features has led
      some authors to suggest that borderline personality disorder is part of the
      bipolar spectrum. Few studies have directly compared patients with bipolar
      disorder and borderline personality disorder. In the present study from the Rhode
      Island Methods to Improve Diagnostic Assessment and Services project, we compared
      these 2 groups of patients on demographic, clinical, and family history
      variables. METHOD: From December 1995 to May 2012, 3,600 psychiatric patients
      presenting to the outpatient practice at Rhode Island Hospital (Providence, Rhode
      Island) were evaluated with semistructured diagnostic interviews for DSM-IV Axis
      I and Axis II disorders. The focus of the present study is the 206 patients with
      DSM-IV major depressive disorder and borderline personality disorder (MDD-BPD)
      and 62 patients with DSM-IV bipolar II depression without borderline personality
      disorder. RESULTS: The patients with MDD-BPD were significantly more often
      diagnosed with posttraumatic stress disorder (P < .001), a current substance use
      disorder (P < .01), somatoform disorder (P < .05), and other nonborderline
      personality disorder (P < .05). Clinical ratings of anger, anxiety, paranoid
      ideation, and somatization were significantly higher in the MDD-BPD group (all P
      < .01). The MDD-BPD patients were rated significantly lower on the Global
      Assessment of Functioning (P < .001), their current social functioning was poorer
      (P < .01), and they made significantly more suicide attempts (P < .01). The
      patients with bipolar II depression had a significantly higher morbid risk for
      bipolar disorder in their first-degree relatives than the MDD-BPD patients (P <
      .05). CONCLUSIONS: Patients diagnosed with bipolar II depression and major
      depressive disorder with comorbid borderline personality disorder differed on a
      number of clinical and family history variables, thereby supporting the validity
      of this distinction.

PMID- 24107760
TI  - SSRI versus bupropion effects on symptom clusters in suicidal depression: post
      hoc analysis of a randomized clinical trial.
AB  - OBJECTIVE: Identifying the depression symptoms most closely associated with
      suicidal thoughts and which medications provide the fastest depression relief may
      help suicide prevention. METHOD: Post hoc analysis of data from a randomized,
      double-blind, 8-week clinical trial of the selective serotonin reuptake inhibitor
      paroxetine controlled release (n = 36) versus the norepinephrine-dopamine
      reuptake inhibitor bupropion extended release (n = 38) was conducted in patients
      with DSM-IV major depressive disorder and past suicide attempt or current
      suicidal thoughts. Treatment effects on Hamilton Depression Rating Scale (HDRS)
      and Beck Depression Inventory symptom clusters were compared. We hypothesized
      that paroxetine would demonstrate a superior effect on nonsuicidal,
      affective/cognitive depression symptom clusters that our prior work found to be
      associated with suicidal thoughts and attempts. Data were collected from February
      2005 to January 2010. RESULTS: There was a treatment main effect on HDRS psychic
      depression (depressed mood, guilt, retardation, helpless, hopeless, worthless)
      (estimate = -2.2; 95% CI, -3.2 to -1.1; t67.16 = -4.01; P < .001), one of the
      clusters most strongly correlated to suicidal ideation. The net drug effect
      demonstrated that mean psychic depression score was 2.2 points lower after 1 week
      of paroxetine compared to bupropion treatment. The significance level of this
      effect was P < .001 at weeks 1 and 2, P = .012 at week 3 and P = .051 at week 4.
      Results for other depression scale factors were nonsignificant (P > .05).
      CONCLUSIONS: The results require replication but suggest a pathway by which
      selective serotonin reuptake inhibitor treatment may exert a stronger effect
      compared with norepinephrine-dopamine reuptake inhibitor treatment on reduction
      of suicidal thoughts during initial weeks of pharmacotherapy in these higher risk
      patients. TRIAL REGISTRATION: ClinicalTrials.gov identifier: NCT00429169.

PMID- 24107762
TI  - Prediction of suicidal behavior in clinical research by lifetime suicidal
      ideation and behavior ascertained by the electronic Columbia-Suicide Severity
      Rating Scale.
AB  - OBJECTIVE: To evaluate whether lifetime suicidal ideation with intention to act
      and/or suicidal behaviors reported at baseline predict risk of prospectively
      reporting suicidal behavior during subsequent study participation. METHOD: Data
      from studies using the electronic Columbia-Suicide Severity Rating Scale (eC
      SSRS) to prospectively monitor suicidal ideation and behaviors between September
      2009 and May 2011 were analyzed. Studies included patients with major depressive
      disorder, insomnia, posttraumatic stress disorder, epilepsy, and fibromyalgia.
      Records for 35,224 eC-SSRS assessments were extracted. Incomplete assessments and
      eC-SSRS records from patients missing a baseline assessment or with no
      prospective follow-up assessments were excluded. Baseline lifetime eC-SSRS
      reports were categorized as negative (no lifetime ideation with intent to act or
      prior suicidal behavior) or positive (lifetime ideation with intent to act but no
      prior behavior, no ideation with intent to act but prior behavior, or both
      lifetime ideation with intent and prior behavior). RESULTS: 3,776 patients
      completed a baseline and 1 or more follow-up assessments. The mean follow-up
      period was 64 days. Of patients with negative lifetime reports, 2.4% subsequently
      reported suicidal behavior during study participation, compared to 12.0% of
      patients with lifetime ideation with intent only (OR = 5.55; 95% CI, 2.65-11.59),
      9.6% of patients with lifetime behavior only (OR = 4.33; 95% CI, 2.94-6.39), and
      18.3% of patients with both (OR = 9.13; 95% CI, 6.47-12.88). Sensitivity and
      specificity of positive reports for identifying suicidal behaviors were 0.67 and
      0.76, respectively. CONCLUSIONS: Patients reporting lifetime suicidal ideation
      with intent to act and/or prior suicidal behavior at baseline are 4 to 9 times
      more likely to prospectively report suicidal behavior during study participation.

PMID- 24107763
TI  - Inhibitory neural activity predicts response to cognitive-behavioral therapy for
      posttraumatic stress disorder.
AB  - OBJECTIVE: Despite cognitive-behavioral therapy (CBT) being an effective
      treatment for posttraumatic stress disorder (PTSD), many patients do not respond
      to CBT. Understanding the neural bases of treatment response may inform treatment
      refinement, thereby improving treatment response rates. Adequate working memory
      function is proposed to enable engagement in CBT. METHOD: This study employed a
      Go/No-Go task to examine inhibitory function and its functional brain correlates
      as predictors of response to CBT in PTSD. Participants were recruited between
      October 2003 and May 2005. Thirteen treatment-seeking patients who met DSM-IV
      criteria for PTSD completed the Go/No-Go task while undergoing functional
      magnetic resonance imaging (fMRI), after which they entered 8 once-weekly
      sessions of CBT. PTSD severity was measured before treatment and again at 6
      months following treatment completion using the Clinician-Administered PTSD Scale
      (primary outcome measure). RESULTS: After controlling for initial PTSD severity
      and ongoing depressive symptoms, greater activity in left dorsal striatal (Z =
      3.19, P = .001) and frontal (Z = 3.03, P = .001) networks during inhibitory
      control was associated with lower PTSD symptom severity after treatment,
      suggesting better treatment response. CONCLUSIONS: These results suggest that
      neural circuitry underpinning inhibitory control plays a role in the outcome of
      CBT for patients with PTSD. TRIAL REGISTRATION: anzctr.org Identifier:
      ACTRN12610000017022.

PMID- 24107765
TI  - Antipsychotic treatment and the occurrence of venous thromboembolism: a 10-year
      nationwide registry study.
AB  - OBJECTIVE: To examine the association between antipsychotic use and venous
      thromboembolism (VTE) in a Taiwan population. METHOD: We conducted a nested case
      control study using the National Health Insurance Research Database in Taiwan. A
      total of 2,162 cases with VTE (defined as pulmonary embolism and infarction [ICD
      9-CM-code: 415.1] or deep vein thrombosis [ICD-9-CM-codes: 451.1x, 451.81, or
      453.8]) and 12,966 matched controls were identified from 2001 to 2010.
      Antipsychotic exposure status was measured, and potential confounding factors
      were adjusted for in the analyses. Conditional logistic regressions were applied
      to determine the effect of antipsychotic use on VTE. RESULTS: Current
      antipsychotic use was associated with an increased risk for VTE (adjusted odds
      ratio [AOR] = 1.52; 95% CI, 1.19-1.93). Among current antipsychotic users, new
      users had a higher risk of VTE (AOR = 3.26; 95% CI, 2.06-5.17), whereas the risk
      among continuous users was modest but not statistically significant (AOR = 1.18;
      95% CI, 0.89-1.56). CONCLUSIONS: The results demonstrated an increased risk of
      VTE among subjects with current antipsychotic use. Antipsychotic drugs should be
      prescribed with caution and attention to the increased risk of VTE. The
      underlying mechanisms related to the effect of antipsychotics on VTE development
      warrant further investigation.

PMID- 24107766
TI  - Specific parental depression symptoms as risk markers for new-onset depression in
      high-risk offspring.
AB  - OBJECTIVE: To disaggregate the depression construct and investigate whether
      specific depression symptoms in parents with a history of recurrent depression
      are clinical risk markers for future depression in their high-risk offspring. Our
      hypothesis was that parental symptoms of the type that might impact offspring
      would most likely be of greatest importance. METHOD: Data were drawn from a
      longitudinal high-risk family study. Families were mainly recruited from primary
      care and included 337 parent-child dyads. Parents had a history of recurrent DSM
      IV unipolar depression and were aged 26-55 years. Their offspring (197 female and
      140 male) were aged 9-17 years. Three assessments were conducted between April
      2007 and April 2011. Ninety-one percent of families (n = 305) provided full
      interview data at baseline and at least 1 follow-up, of which 291 were included
      in the primary analysis. The main outcome measure was new-onset DSM-IV mood
      disorder in the offspring, which was assessed using the Child and Adolescent
      Psychiatric Assessment. RESULTS: Of the 9 DSM-IV depression symptoms, parental
      change in appetite or weight, specifically loss of appetite or weight, most
      strongly predicted new-onset mood disorder (odds ratio [OR] = 4.47; 95% CI, 2.04
      9.79; P < .001) and future depression symptoms in the offspring (beta = 0.12; B =
      0.21; 95% CI, 0.00-0.42; P = .050). The cross-generational association was not
      accounted for by measures of parental depression severity (total depression
      symptom score, episode recurrence, age at onset, and past impairment or
      hospitalization) or other potential confounds (parent physical health, eating
      disorder, or medication). CONCLUSIONS: Findings from this study suggest that loss
      of appetite or weight in parents with a history of recurrent depression is a
      marker of risk for depression in their offspring. The findings highlight the
      importance of examining depression heterogeneity. The biological and
      environmental mechanisms underlying this finding require investigation.

PMID- 24107764
TI  - Effect of psychostimulants on brain structure and function in ADHD: a qualitative
      literature review of magnetic resonance imaging-based neuroimaging studies.
AB  - OBJECTIVE: To evaluate the impact of therapeutic oral doses of stimulants on the
      brains of ADHD subjects as measured by magnetic resonance imaging (MRI)-based
      neuroimaging studies (morphometric, functional, spectroscopy). DATA SOURCES: We
      searched PubMed and ScienceDirect through the end of calendar year 2011 using the
      keywords (1) psychostimulants or methylphenidate or amphetamine, and (2)
      neuroimaging or MRI or fMRI, and (3) ADHD or ADD or attention
      deficit/hyperactivity disorder or attention deficit hyperactivity disorder. STUDY
      SELECTION: We included only English language articles with new data from case
      control or placebo controlled studies that examined attention
      deficit/hyperactivity disorder (ADHD) subjects on and off psychostimulants (as
      well as 5 relevant review articles). DATA EXTRACTION: We combined details of
      study design and medication effects in each imaging modality. RESULTS: We found
      29 published studies that met our criteria. These included 6 structural MRI, 20
      functional MRI studies, and 3 spectroscopy studies. Methods varied widely in
      terms of design, analytic technique, and regions of the brain investigated.
      Despite heterogeneity in methods, however, results were consistent. With only a
      few exceptions, the data on the effect of therapeutic oral doses of stimulant
      medication suggest attenuation of structural and functional alterations found in
      unmedicated ADHD subjects relative to findings in controls. CONCLUSIONS: Despite
      the inherent limitations and heterogeneity of the extant MRI literature, our
      review suggests that therapeutic oral doses of stimulants decrease alterations in
      brain structure and function in subjects with ADHD relative to unmedicated
      subjects and controls. These medication-associated brain effects parallel, and
      may underlie, the well-established clinical benefits.

PMID- 24107767
TI  - National trends in the office-based prescription of schedule II opioids.
AB  - OBJECTIVE: To investigate national trends and patterns in opioid prescription
      within office-based medical practice. METHOD: An analysis is presented of 1995
      2010 data from the National Ambulatory Medical Care Survey, focusing on overall
      and stratified trends in the percentage of medical visits involving prescriptions
      for Schedule II opioids. Among visits with opioid prescriptions in 2003-2010,
      first-time visits were also compared to return visits, and visits in which pain
      was the primary complaint were compared to visits with other primary complaints.
      RESULTS: Among all office visits, the percentage with an opioid prescription
      increased from 0.65% in 1995-1998 to 2.63% in 2007-2010 (odds ratio [OR] = 8.01;
      95% CI, 4.96-12.94). During the study period (1995-2010), opioid prescriptions
      significantly increased in visits by male patients (OR = 6.54; 95% CI, 3.21
      13.31); female patients (OR = 9.38; 95% CI, 6.70-13.14); and patients aged 18-35
      years (OR = 5.82; 95% CI, 2.59-13.10), 36-64 years (OR = 8.30; 95% CI, 4.63
      14.86), and >= 65 years (OR = 8.85; 95% CI, 6.13-12.77), but not <= 17 years (OR
      = 1.52; 95% CI, 0.50-4.63). Prescriptions for opioids also significantly
      increased in visits by patients with clinical depression (OR = 9.96; 95% CI, 5.45
      18.21) or anxiety (OR = 10.99; 95% CI, 5.02-24.06) diagnoses. However, a
      significant decline occurred in opioid prescriptions in visits among patients
      with substance use diagnoses (OR = 0.10; 95% CI, 0.00-3.30). The number of opioid
      prescriptions rose faster among patients making a first visit (OR = 23.36; 95%
      CI, 11.82-46.17) versus a return visit (OR = 7.26; 95% CI, 4.38-12.03).
      CONCLUSIONS: A substantial increase occurred between 1995 and 2010 in opioid
      prescriptions in office-based medical visits, especially in visits by middle-aged
      and older adults and by patients making their first visit to the treating
      physician. These trends suggest that physicians have pursued greater pain control
      despite potential risks of nonmedical use of prescription opioids.

PMID- 24107768
TI  - Antidepressant use in pregnancy and risk of autism spectrum disorders: a critical
      examination of the evidence.

PMID- 24107769
TI  - Improving patient outcomes in schizophrenia: achieving remission, preventing
      relapse, and measuring success.
AB  - Too many patients with schizophrenia do not achieve the ultimate goal of
      treatment-recovery. The first step to recovery is achieving response to treatment
      for the acute psychotic episode. Clinicians should routinely use rating scales to
      measure treatment response. The next phase is remission of symptoms, which is one
      of the criteria for recovery. Relapses, however, can disrupt remission and hinder
      recovery by causing rehospitalization, treatment resistance, and loss of gains in
      function. Medication adherence plays a major role in preventing relapses so that
      patients can maintain remission and work toward recovery. Clinicians should
      educate patients about adherence and consider treatment options that will improve
      adherence. Recovery is attained when patients experience symptom remission,
      vocational role fulfillment, independent living, and social relationships for at
      least 2 years. The proportion of patients who reach recovery can be increased
      when clinicians focus on treatment adherence, consistent symptom measurement, and
      appropriate treatment plans tailored to each patient. 

PMID- 24107770
TI  - Strategies for managing the risks associated with ADHD medications.
AB  - College students with ADHD may need help to overcome symptoms that make studying,
      organizing and completing projects, and managing their time a challenge. In order
      to properly treat these patients, clinicians must correctly assess ADHD and
      comorbid conditions using rating scales and educate patients about their
      responsibility to reach their treatment goals and to properly use and protect
      their medication. Patients with past substance use may require treatment options
      that are less likely to be misused, such as a nonstimulant or long-acting
      stimulants. Throughout the treatment process, clinicians should continue to
      monitor symptoms and side effects with regular office visits and random testing,
      watching for signs of drug misuse. 

PMID- 24107771
TI  - Famotidine augmentation in schizophrenia: hope or hype?

PMID- 24107772
TI  - Effects of stroke rehabilitation on incidence of poststroke depression: a
      population-based cohort study.
AB  - OBJECTIVE: To investigate the effects of rehabilitation intervention provided
      within the first 3 months after admission for stroke on the incidence of
      poststroke depression (diagnosed according to ICD-9-CM code 296, 309, or 311, or
      A-code A212 or A219). METHOD: This population-based cohort study examined medical
      claim data of a random sample of 1 million insured people registered in 2000 in
      Taiwan. Between 2000 and 2005, there were 7,677 patients admitted as first-time
      stroke patients. Of these, 1,285 (16.7%) received a rehabilitation regimen within
      the first 3 months of admission for stroke. The other 83.3% of patients (n =
      6,482) belonged to the control group. All study subjects were followed to the end
      of 2009 to identify any ambulatory treatment for depression as the end point. The
      incidence density of poststroke depression was calculated assuming a Poisson
      process. A Cox proportional hazard model was used to estimate the relative risk
      of poststroke depression in relation to receipt of rehabilitation. RESULTS: Over
      a 10-year follow-up, 75 patients (5.8%) with rehabilitation and 566 controls
      (8.7%) developed poststroke depression, representing incidence densities of 11.3
      and 18.5 per 1,000 person-years, respectively. After analyses were controlled for
      potential confounders, rehabilitation was found to significantly reduce the risk
      of poststroke depression, with a hazard ratio (HR) of 0.57 (95% CI, 0.45-0.73).
      The effect was greater for men (HR = 0.52; 95% CI, 0.37-0.71), especially for
      elderly men (HR = 0.45; 95% CI, 0.28-0.71), than for women (HR = 0.69; 95% CI,
      0.47-1.02). CONCLUSIONS: Stroke rehabilitation intervention in the first 3 months
      after admission for stroke may significantly reduce the risk of poststroke
      depression. Although this beneficial effect appears to be greater for men than
      for women, clinicians should also be alert for poststroke depression occurring in
      women.

PMID- 24107773
TI  - Fundamental differences in promoter CpG island DNA hypermethylation between human
      cancer and genetically engineered mouse models of cancer.
AB  - Genetic and epigenetic alterations are essential for the initiation and
      progression of human cancer. We previously reported that primary human
      medulloblastomas showed extensive cancer-specific CpG island DNA hypermethylation
      in critical developmental pathways. To determine whether genetically engineered
      mouse models (GEMMs) of medulloblastoma have comparable epigenetic changes, we
      assessed genome-wide DNA methylation in three mouse models of medulloblastoma. In
      contrast to human samples, very few loci with cancer-specific DNA
      hypermethylation were detected, and in almost all cases the degree of methylation
      was relatively modest compared with the dense hypermethylation in the human
      cancers. To determine if this finding was common to other GEMMs, we examined a
      Burkitt lymphoma and breast cancer model and did not detect promoter CpG island
      DNA hypermethylation, suggesting that human cancers and at least some GEMMs are
      fundamentally different with respect to this epigenetic modification. These
      findings provide an opportunity to both better understand the mechanism of
      aberrant DNA methylation in human cancer and construct better GEMMs to serve as
      preclinical platforms for therapy development. 

PMID- 24107774
TI  - Autoimmune attack takes your breath away.
AB  - Autoimmune targeting of a lung-specific protein can cause interstitial lung
      disease (Shum et al., this issue). 

PMID- 24107775
TI  - A new PERKspective on neurodegeneration.
AB  - Targeting stress-induced kinases that regulate protein synthesis may be a new
      therapeutic strategy for treating neurodegenerative diseases. 

PMID- 24107776
TI  - Phytosterols promote liver injury and Kupffer cell activation in parenteral
      nutrition-associated liver disease.
AB  - Parenteral nutrition-associated liver disease (PNALD) is a serious complication
      of PN in infants who do not tolerate enteral feedings, especially those with
      acquired or congenital intestinal diseases. Yet, the mechanisms underlying PNALD
      are poorly understood. It has been suggested that a component of soy oil (SO)
      lipid emulsions in PN solutions, such as plant sterols (phytosterols), may be
      responsible for PNALD, and that use of fish oil (FO)-based lipid emulsions may be
      protective. We used a mouse model of PNALD combining PN infusion with intestinal
      injury to demonstrate that SO-based PN solution causes liver damage and hepatic
      macrophage activation and that PN solutions that are FO-based or devoid of all
      lipids prevent these processes. We have furthermore demonstrated that a factor in
      the SO lipid emulsions, stigmasterol, promotes cholestasis, liver injury, and
      liver macrophage activation in this model and that this effect may be mediated
      through suppression of canalicular bile transporter expression (Abcb11/BSEP,
      Abcc2/MRP2) via antagonism of the nuclear receptors Fxr and Lxr, and failure of
      up-regulation of the hepatic sterol exporters (Abcg5/g8/ABCG5/8). This study
      provides experimental evidence that plant sterols in lipid emulsions are a major
      factor responsible for PNALD and that the absence or reduction of plant sterols
      is one of the mechanisms for hepatic protection in infants receiving FO-based PN
      or lipid minimization PN treatment. Modification of lipid constituents in PN
      solutions is thus a promising strategy to reduce incidence and severity of PNALD.

PMID- 24107777
TI  - Oral treatment targeting the unfolded protein response prevents neurodegeneration
      and clinical disease in prion-infected mice.
AB  - During prion disease, an increase in misfolded prion protein (PrP) generated by
      prion replication leads to sustained overactivation of the branch of the unfolded
      protein response (UPR) that controls the initiation of protein synthesis. This
      results in persistent repression of translation, resulting in the loss of
      critical proteins that leads to synaptic failure and neuronal death. We have
      previously reported that localized genetic manipulation of this pathway rescues
      shutdown of translation and prevents neurodegeneration in a mouse model of prion
      disease, suggesting that pharmacological inhibition of this pathway might be of
      therapeutic benefit. We show that oral treatment with a specific inhibitor of the
      kinase PERK (protein kinase RNA-like endoplasmic reticulum kinase), a key
      mediator of this UPR pathway, prevented UPR-mediated translational repression and
      abrogated development of clinical prion disease in mice, with neuroprotection
      observed throughout the mouse brain. This was the case for animals treated both
      at the preclinical stage and also later in disease when behavioral signs had
      emerged. Critically, the compound acts downstream and independently of the
      primary pathogenic process of prion replication and is effective despite
      continuing accumulation of misfolded PrP. These data suggest that PERK, and other
      members of this pathway, may be new therapeutic targets for developing drugs
      against prion disease or other neurodegenerative diseases where the UPR has been
      implicated. 

PMID- 24107778
TI  - BPIFB1 is a lung-specific autoantigen associated with interstitial lung disease.
AB  - Interstitial lung disease (ILD) is a complex and heterogeneous disorder that is
      often associated with autoimmune syndromes. Despite the connection between ILD
      and autoimmunity, it remains unclear whether ILD can develop from an autoimmune
      response that specifically targets the lung parenchyma. We examined a severe form
      of autoimmune disease, autoimmune polyglandular syndrome type 1 (APS1), and
      established a strong link between an autoimmune response to the lung-specific
      protein BPIFB1 (bactericidal/permeability-increasing fold-containing B1) and
      clinical ILD. Screening of a large cohort of APS1 patients revealed
      autoantibodies to BPIFB1 in 9.6% of APS1 subjects overall and in 100% of APS1
      subjects with ILD. Further investigation of ILD outside the APS1 disorder
      revealed BPIFB1 autoantibodies present in 14.6% of patients with connective
      tissue disease-associated ILD and in 12.0% of patients with idiopathic ILD. The
      animal model for APS1, Aire-/- mice, harbors autoantibodies to a similar lung
      antigen (BPIFB9); these autoantibodies are a marker for ILD. We found that a
      defect in thymic tolerance was responsible for the production of BPIFB9
      autoantibodies and the development of ILD. We also found that immunoreactivity
      targeting BPIFB1 independent of a defect in Aire also led to ILD, consistent with
      our discovery of BPIFB1 autoantibodies in non-APS1 patients. Overall, our results
      demonstrate that autoimmunity targeting the lung-specific antigen BPIFB1 may
      contribute to the pathogenesis of ILD in patients with APS1 and in subsets of
      patients with non-APS1 ILD, demonstrating the role of lung-specific autoimmunity
      in the genesis of ILD.

PMID- 24107780
TI  - Physical activity and acculturation among U.S. Latinas of childbearing age.
AB  - The majority of Latinas of childbearing age is not sufficiently active; a
      significant health disparity, and is at risk for deleterious health consequences.
      The study's objectives were to explore acculturation and associated factors'
      effect on engagement in physical activity (PA) among Latinas. Based on data (2008
      2011 National Health Interview Survey; N = 7,278), multinomial logistic models
      predicted odds of adherence to 2008 PA Guidelines for Americans. Among 3,386,680
      Latinas, 18 to 47 years, 58.9% (standard error [SE] = 0.0073) met neither aerobic
      nor muscle-strengthening recommendations, after controlling for poverty, income,
      marital status, and competing obligations. Less acculturated Latinas (Spanish
      preferring) were less likely to engage in PA than English-preferring counterparts
      (odds ratio [OR] = 0.57, p < .01). Spanish-preferring foreign-born Latinas have
      substantially smaller odds of meeting PA guidelines than U.S.-born English
      preferring Latinas (OR = 0.3, p < .001). Puerto Ricans and Dominican immigrants
      are least likely to meet guidelines. Latinas are not homogeneous. Country of
      origin and acculturation should be considered in future PA interventions. 

PMID- 24107779
TI  - Systems pharmacology of adverse event mitigation by drug combinations.
AB  - Drugs are designed for therapy, but medication-related adverse events are common,
      and risk/benefit analysis is critical for determining clinical use.
      Rosiglitazone, an efficacious antidiabetic drug, is associated with increased
      myocardial infarctions (MIs), thus limiting its usage. Because diabetic patients
      are often prescribed multiple drugs, we searched for usage of a second drug
      ("drug B") in the Food and Drug Administration's Adverse Event Reporting System
      (FAERS) that could mitigate the risk of rosiglitazone ("drug A")-associated MI.
      In FAERS, rosiglitazone usage is associated with increased occurrence of MI, but
      its combination with exenatide significantly reduces rosiglitazone-associated MI.
      Clinical data from the Mount Sinai Data Warehouse support the observations from
      FAERS. Analysis for confounding factors using logistic regression showed that
      they were not responsible for the observed effect. Using cell biological
      networks, we predicted that the mitigating effect of exenatide on rosiglitazone
      associated MI could occur through clotting regulation. Data we obtained from the
      db/db mouse model agreed with the network prediction. To determine whether
      polypharmacology could generally be a basis for adverse event mitigation, we
      analyzed the FAERS database for other drug combinations wherein drug B reduced
      serious adverse events reported with drug A usage such as anaphylactic shock and
      suicidality. This analysis revealed 19,133 combinations that could be further
      studied. We conclude that this type of crowdsourced approach of using databases
      like FAERS can help to identify drugs that could potentially be repurposed for
      mitigation of serious adverse events. 

PMID- 24107781
TI  - Cultural frames, qualities of life, and the aging self.
AB  - We used the Self-Concept Enhancement Tactician (SCENT) model to explore whether
      older Norwegians and Canadians would tactically self-enhance on qualities
      considered significant within their cultures in their self-perceptions of aging.
      Qualities were measured using the WHOQOL-BREF and WHOQOL-OLD. Self-perceptions of
      aging were measured by the Attitudes to Aging Questionnaire. The study is a
      secondary analysis of data collected in a larger study; 393 older Norwegians and
      202 older Canadians were included. The Norwegian and Canadian group self-enhanced
      their perceptions of psychosocial loss based on harmonious social relationships
      and being part of a larger social group. For self-perceptions of physical change,
      both groups self-enhanced on being self-sufficient and being part of a larger
      social group. Our findings suggest that Norwegians and Canadians are not highly
      individualistic people and also provide evidence of a bicultural self-perception
      of aging. Nurses should consider how cultural and individual perspectives affect
      the care priorities of older people. 

PMID- 24107782
TI  - Incidence of distress and associated factors in women undergoing breast
      diagnostic evaluation.
AB  - The purpose of this study was to identify the incidence of distress and factors
      associated with distress in women undergoing breast diagnostic evaluations. A
      total of 128 women undergoing a breast biopsy at three hospitals completed a set
      of nine standardized instruments. The presence of distress was identified with
      14% having symptoms above the cutoff point for clinical anxiety. In multiple
      regression analyses, trait anxiety alone explained 71% of the State-Trait Anxiety
      Inventory State score. A model with trait anxiety, satisfaction with health care,
      meaning in life, and friend support accounted for 66% of the Hospital Anxiety and
      Depression Scale score for depression. It appears that when faced with a
      potential cancer diagnosis, distress levels are based on personality and self
      evaluation of whether one has the resources to adapt to life with cancer.
      Distress screening protocols need to be routinely included in diagnostic
      radiology appointments. Nurses should implement interventions focusing on
      providing information, facilitating communication, and offering psychosocial
      support. 

PMID- 24107783
TI  - MDR1 is related to intestinal epithelial injury induced by acetylsalicylic acid.
AB  - BACKGROUND/AIMS: Although the cytotoxicity of aspirin against the intestinal
      epithelium is a major clinical problem, little is known about its pathogenesis.
      We assessed the involvement of Multi Drug Resistance (MDR) 1 in intestinal
      epithelial cell injury caused by aspirin using MDR1 gene-transfected Caco2 cells.
      METHODS: Caco2 cells were treated with various concentrations of aspirin for 24
      h. After treatment of Caco2 cells with verapamil, a specific inhibitor of MDR1,
      we assessed the extent of cell injury using a WST-8 assay at 24 h after aspirin
      stimulation. We performed the same procedure in MDR1 gene-transfected Caco2
      cells. To determine the function of MDR1 in the metabolism of aspirin, flux study
      was performed using (14)C-labeled aspirin. RESULTS: The level of aspirin-induced
      cell injury was higher in verapamil-treated Caco2 cells than in control cells and
      was less serious in MDR1-transfected Caco2 cells than in control vector
      transfected cells. The efflux of (14)C-labeled aspirin was higher in verapamil
      treated Caco2 cells than in control cells. CONCLUSION: These data suggest that
      aspirin effux occurs through the MDR1 transporter and that the MDR1 transporter
      is involved in the pathogenesis of aspirin-induced cell injury.

PMID- 24107784
TI  - Prone to survive and the priority rule in science.

PMID- 24107785
TI  - Echocardiographic markers of left ventricular dysfunction among men with
      uncontrolled hypertension and stage 3 chronic kidney disease.
AB  - BACKGROUND: Current guidelines for the management of arterial hypertension (AH)
      emphasize the importance of diagnosing subclinical organ damage, which determines
      cardiovascular prognosis. The aim of our study was to evaluate the prevalence of
      left ventricular hypertrophy (LVH), LV geometry patterns, and LV
      systolic/diastolic dysfunction among men with uncontrolled AH and chronic kidney
      disease (CKD) stages 3A and 3B. MATERIAL/METHODS: The study group included 256
      men with essential AH. Glomerular filtration rate (eGFR) was calculated by the
      simplified MDRD equation. Left ventricular structure and function were assessed
      using echocardiography. RESULTS: Target blood pressure values were observed in 44
      (17.2%) patients. In the studied group, eGFR <60 ml/min/1.73 m2 was found in 67
      (26.2%) subjects. Forty-nine (19.14%) patients were in stage 3A and 18 patients
      (7.03%) in stage 3B of CKD. We demonstrated that LVEDD, LA, RWT, and LVMI ECHO
      parameters were distinctly higher (p<0.05) in poorly controlled hypertensive
      patients in CKD stage 3B when compared with patients in CKD stage 3A. A
      significantly higher prevalence of LVH, including LV eccentric hypertrophy, was
      observed in stage 3B when compared to stage 3A of CKD (p<0.05). LVEF and E/A
      ratio decreased along with the decline of renal function (p<0.05). CONCLUSIONS:
      Relationships between eGFR values and echocardiographic abnormalities of LV
      structure and function observed by us support the division of CKD stage 3 into 2
      substages, 3A and 3B, as proposed by recently published guidelines.
      Intensification of therapeutic regimen in the CKD 3B substage is therefore
      crucial from both cardiological and nephrological perspectives.

PMID- 24107786
TI  - Comparison of the perinatal outcomes after laparoscopic myomectomy versus
      abdominal myomectomy.
AB  - BACKGROUND/AIMS: To compare the perinatal outcomes after laparoscopic myomectomy
      (LM) versus abdominal myomectomy (AM). METHODS: The medical records of 105
      Japanese females who delivered after myomectomy from 2004 to 2012 at Osaka
      Medical College were reviewed retrospectively. RESULTS: Of the 105 females who
      delivered after myomectomy, 48 had undergone LM and 57 had undergone AM. There
      were no significant differences in the perinatal outcomes including the rates of
      emergency cesarean sections, preterm deliveries, placental abnormalities,
      pregnancy-induced hypertension, low Apgar score, non-reassuring fetal heart rate
      patterns, and intrauterine fetal death. No significant difference was observed in
      the incidence of post-partum hemorrhage. There was no uterine rupture in either
      group. 15 (31%) of the females who had LM were candidates for transvaginal
      delivery, and 14 delivered vaginally (93% success rate). In contrast, 20 (35%) of
      the females who had AM were candidates for transvaginal delivery, and 19
      delivered vaginally (95% success rate). CONCLUSION: There were no significant
      differences in the perinatal outcomes between the females who had LM and AM.
      Moreover, both groups had a high rate of successful transvaginal delivery after
      selecting the appropriate candidates.

PMID- 24107787
TI  - Optotransfection of mammalian cells based on a femtosecond laser and facilitated
      by gold nanorods.
AB  - The optotransfection of cells based on a femtosecond laser has attracted much
      attention owing to its high transfection efficiency and high cell viability since
      its first report by Konig. However, the low throughput in the original method
      also limits its use in practical applications. Gold nanoparticles (GNPs) have
      been reported to function as local receivers of light to relax the requirement of
      accurate optical alignment for the optotransfection of single cells. However, the
      visible light used in such work is not suitable for penetrating deep tissues in
      certain applications. In this study, we employed gold nanorods (GNRs) and an
      infrared femtosecond laser at the wavelength of 980 nm to realize
      optotransfection of cells with GFP. It was found that the surface coating of GNRs
      exhibited a significant effect on the process of cell permeabilization. 

PMID- 24107788
TI  - Child mortality in the Netherlands in the past decades: an overview of external
      causes and the role of public health policy.
AB  - Among European countries, the Netherlands has the second lowest child mortality
      rate from external causes. We present an overview, discuss possible explanations,
      and suggest prevention measures. We analyzed mortality data from all deceased
      children aged 0-19 years for the period 1969-2011. Child mortality declined in
      the past decades, largely from decreases in road traffic accidents that followed
      government action on traffic safety. Accidental drowning also showed a downward
      trend. Although intentional self-harm showed a significant increase, other
      external causes of mortality, including assault and fatal child abuse, remained
      constant. Securing existing preventive measures and analyzing the circumstances
      of each child's death systematically through Child Death Review may guide further
      reduction in child mortality. 

PMID- 24107789
TI  - A short note on e-cigarette issues: harm reduction, re-normalization, and Big
      Tobacco.

PMID- 24107790
TI  - Securing support for eye health policy in low- and middle-income countries:
      identifying stakeholders through a multi-level analysis.
AB  - This article empirically evaluates advocacy in low- and middle-income countries
      as a key tool for raising policy priority and securing high-level decision maker
      support in eye health. We used a unique data set based on a survey conducted by
      World Health Organization in 2011 on eye care and prevention of blindness in 82
      low- and middle-income countries. The theoretical framework derives from the idea
      that a plethora of stakeholders at local and global level pressure national
      governments, acting in economic and the political spheres. Previously, eye care
      has not been investigated in such a framework. We found structural differences
      across countries with different income levels and proposed policy recommendations
      to secure high-level decision makers' support for promoting eye health. Three
      case studies suggest that, in order to secure more support and resources for eye
      health, domestic and international stakeholders must strengthen their engagement
      with ministries of health at political and above all economic levels. 

PMID- 24107791
TI  - How reliable are lower-limb kinematics and kinetics during a drop vertical jump?
AB  - PURPOSE: As drop vertical jumps (DVJ) are widely used as a screening task, the
      assessment of the reliability of lower-limb biomechanical parameters during DVJ
      is important. The aim of this study was to assess the reliability of the
      kinematic and kinetic peak values as well as of the waveforms for lower-limb
      parameters obtained with the Liverpool John Moores University biomechanical model
      (LJMU model) during performance of DVJ. METHODS: The reliability was analyzed by
      calculating the intertrial (o(trial)), intersession (o(sess)), and intertherapist
      (o(ther)) errors of hip and knee joint parameters in a repeated-measures design
      including two therapists and a total of six sessions. RESULTS: The results showed
      o(trial) that ranged from 1.1 degrees  to 3.5 degrees  for all peak kinematic
      parameters and from 3.6 to 12.9 N . m for all peak kinetic parameters. The o of
      the peak values ranged from 1.9 degrees  to 5.7 degrees  for all angles and from
      5.4 to 19.8 N . m for the hip and knee joint moments in all planes. The o(sess)
      of the peak values ranged from 2.7 degrees  to 6.4 degrees  for all angles and
      from 5.8 to 22.4 N . m for all moments. Most of the kinematic and kinetic peak
      parameters had o(ther-trial) <= 2.0 degrees  and 4.3 N . m, respectively,
      suggesting a small extrinsic variability. Furthermore, the entire waveforms also
      showed a rather high o(trial) relative to other types of variability.
      CONCLUSIONS: The present findings indicated that DVJ kinetics and kinematics show
      small extrinsic variability. The reported errors are useful for clinical
      interpretation processes of DVJ performance as screening task for injury risk and
      rehabilitation outcome taking into consideration the different types of
      measurement error over time.

PMID- 24107795
TI  - Preface.

PMID- 24107792
TI  - Molecular neuropsychology: creation of test-specific blood biomarker algorithms.
AB  - BACKGROUND: Prior work on the link between blood-based biomarkers and cognitive
      status has largely been based on dichotomous classifications rather than detailed
      neuropsychological functioning. The current project was designed to create serum
      based biomarker algorithms that predict neuropsychological test performance.
      METHODS: A battery of neuropsychological measures was administered. Random forest
      analyses were utilized to create neuropsychological test-specific biomarker risk
      scores in a training set that were entered into linear regression models
      predicting the respective test scores in the test set. Serum multiplex biomarker
      data were analyzed on 108 proteins from 395 participants (197 Alzheimer patients
      and 198 controls) from the Texas Alzheimer's Research and Care Consortium.
      RESULTS: The biomarker risk scores were significant predictors (p < 0.05) of
      scores on all neuropsychological tests. With the exception of premorbid
      intellectual status (6.6%), the biomarker risk scores alone accounted for a
      minimum of 12.9% of the variance in neuropsychological scores. Biomarker
      algorithms (biomarker risk scores and demographics) accounted for substantially
      more variance in scores. Review of the variable importance plots indicated
      differential patterns of biomarker significance for each test, suggesting the
      possibility of domain-specific biomarker algorithms. CONCLUSIONS: Our findings
      provide proof of concept for a novel area of scientific discovery, which we term
      'molecular neuropsychology'.

PMID- 24107793
TI  - Current concepts in the diagnosis and classification of renal dysfunction in
      cirrhosis.
AB  - BACKGROUND: Renal dysfunction is one of the most common complications of
      cirrhosis with high morbidity and mortality. SUMMARY: In subjects with cirrhosis,
      renal dysfunction can present either as a direct consequence of cirrhosis (e.g.
      hepatorenal syndrome type I and type II) or secondary to etiologies other than
      cirrhosis (chronic kidney disease due to diabetic nephropathy, prerenal
      azotemia), or patients with cirrhosis may have renal dysfunction resulting
      directly from cirrhosis and an underlying chronic kidney disease. KEY MESSAGES:
      Given the challenges in the differential diagnosis of renal dysfunction and
      insufficient accuracy of serum creatinine and creatinine-based glomerular
      filtration rate estimating equations in cirrhosis, there is an urgent need for
      more accurate biomarkers of renal dysfunction in this population. This review
      will discuss novel concepts for the diagnosis and classification of renal
      dysfunction in cirrhosis to overcome at least some of the diagnostic and
      therapeutic challenges. Additionally, a new classification will be proposed for
      renal dysfunction in cirrhosis.

PMID- 24107796
TI  - An individual, community-based treatment for obese children and their families:
      the solution-focused approach.
AB  - BACKGROUND: This study evaluates an individual, community-based treatment for
      obese children and their families. In this program, a treatment team applied
      solution-focused techniques to develop a custom-made treatment plan in
      collaboration with the participants. The treatment plan consisted of community
      based lifestyle activities. METHODS: 559 obese children with an average BMI z
      score of 2.76 +/- 0.54 took part in the 12-month study, and 372 children with an
      average BMI z-score of 2.75 +/- 0.52 took part in the 24-month study. At the
      start of the study, ethnicity and special school needs were recorded. Before,
      after 12 months, and after 24 months of the treatment, body weight and height
      were measured. The effect of the treatment on body weight was evaluated using BMI
      z-scores. RESULTS: 291 children (52%) completed 12 months of treatment, whereas
      22 children (4%) were dismissed earlier due to a good response. After 12 months,
      the children showed a significant decrease in BMI z-score by 0.16 (95% confidence
      interval (CI) 0.11-0.20; p < 0.005). After 24 months, 103 children (28%) were
      participating in the program, with a significant decrease in BMI z-score of 0.15
      (95% CI 0.07-0.22; p < 0.005). 50 children (13%) were dismissed before the end of
      the second year due to significant weight loss (standard deviation z-score
      reduction -0.38; 95% CI 0.30-0.46; p < 0.005; with an average treatment duration
      of 12.9 +/- 6.4 months). There was a negative correlation of age and reduction in
      BMI z-score: children younger than 6 years showed a decrease in BMI z-score of
      0.45 (95% CI 0.26-0.65) and 0.31 (95% CI 0.11-0.53) after 12 and after 24 months,
      respectively. CONCLUSIONS: Children showed a significant decrease in BMI z-score
      after the treatment. We found a negative correlation of age and weight loss.
      Special attention to patients with a high risk of drop-out might further improve
      these results. We advise a referral to obesity treatment as early as possible
      since a 'wait and see' policy might have adverse results in obese children.

PMID- 24107798
TI  - On-spot brilliant cresyl blue staining in fine needle aspiration, a novel
      technique for cytological diagnosis.
AB  - OBJECTIVE: Application of on-spot staining with brilliant cresyl blue, a
      supravital stain, was investigated in fine needle aspirates from breast, lymph
      node and thyroid. STUDY DESIGN: Patients with palpable breast lumps, lymph nodes
      and thyroid nodules were included in the study. Brilliant cresyl blue was used to
      stain the smears, which were evaluated for smear adequacy as well as cytological
      diagnosis. Smears were decolorized and subjected to Pap and/or HE staining for
      comparison. RESULTS: Smears which were deemed hemorrhagic on the first attempt
      with brilliant cresyl blue correlated with Pap staining; then sites were
      reaspirated within minutes to obtain satisfactory cellular smears.
      Morphologically, cells which were designated malignant on supravital staining
      were mostly malignant on Pap/HE staining. CONCLUSION: On-spot brilliant cresyl
      blue staining increases the diagnostic potential on preliminary examination by
      decreasing the staining time and is as good as conventional stains in exhibiting
      cellular morphology.

PMID- 24107799
TI  - Mechanics of metal-catecholate complexes: the roles of coordination state and
      metal types.
AB  - There have been growing evidences for the critical roles of metal-coordination
      complexes in defining structural and mechanical properties of unmineralized
      biological materials, including hardness, toughness, and abrasion resistance.
      Their dynamic (e.g. pH-responsive, self-healable, reversible) properties inspire
      promising applications of synthetic materials following this concept. However,
      mechanics of these coordination crosslinks, which lays the ground for predictive
      and rational material design, has not yet been well addressed. Here we present a
      first-principles study of representative coordination complexes between metals
      and catechols. The results show that these crosslinks offer stiffness and
      strength near a covalent bond, which strongly depend on the coordination state
      and type of metals. This dependence is discussed by analyzing the nature of
      bonding between metals and catechols. The responsive mechanics of metal
      coordination is further mapped from the single-molecule level to a networked
      material. The results presented here provide fundamental understanding and
      principles for material selection in metal-coordination-based applications.

PMID- 24107800
TI  - Human papillomavirus genotype distribution in cytologically screened women from
      northwest Germany.
AB  - INTRODUCTION: In this study, we evaluate the distribution of 24 human
      papillomavirus (HPV) genotypes in a cohort of 3,381 cytologically screened women
      from a rural area of northwest Germany, in correlation to cytological diagnoses
      and histological outcomes. MATERIALS AND METHODS: We present a retrospective
      study in which the HPV-genotyping results of women who attended the German
      cervical screening program were correlated to cytological diagnosis and
      histological outcome. RESULTS: HPV genotyping showed marked differences among
      cervical lesions. Although HPV-51 was common in all cervical lesions, it was
      rarely detected as single-type HPV infection in high-grade cervical
      intraepithelial neoplasia (CIN)3 (2/118 cases). HPV-16 and 18 were more common in
      CIN3 (57.6%) than in CIN2 (21.8%), but they were absent in 42.4% of all CIN3
      lesions in our cohort. DISCUSSION: Our data show that HPV-16, HPV-31, HPV-51, HPV
      53 and HPV-42 are the most prevalent HPV types in the different cervical lesions
      in this region of northwest Germany. HPV genotyping has been shown to be a
      powerful tool to triage atypical squamous cells of undetermined significance
      lesions. Considering the observed heterogeneity of HPV types in CIN2, it could
      also be useful to triage CIN2+ lesions. Our results underline the usefulness of a
      morphologically controlled screening program with HPV genotyping as a powerful
      additional tool.

PMID- 24107797
TI  - Whole brain radiation-induced vascular cognitive impairment: mechanisms and
      implications.
AB  - Mild cognitive impairment is a well-documented consequence of whole brain
      radiation therapy (WBRT) that affects 40-50% of long-term brain tumor survivors.
      The exact mechanisms for the decline in cognitive function after WBRT remain
      elusive and no treatment or preventative measures are available for use in the
      clinic. Here, we review recent findings indicating how changes in the
      neurovascular unit may contribute to the impairments in learning and memory. In
      addition to affecting neuronal development, WBRT induces profound capillary
      rarefaction within the hippocampus - a region of the brain important for learning
      and memory. Therapeutic strategies such as hypoxia, which restore the capillary
      density, result in the rescue of cognitive function. In addition to decreasing
      vascular density, WBRT impairs vasculogenesis and/or angiogenesis, which may also
      contribute to radiation-induced cognitive decline. Further studies aimed at
      uncovering the specific mechanisms underlying these WBRT-induced changes in the
      cerebrovasculature are essential for developing therapies to mitigate the
      deleterious effects of WBRT on cognitive function.

PMID- 24107801
TI  - Expression of TP53 mutation-associated microRNAs predicts clinical outcome in
      head and neck squamous cell carcinoma patients.
AB  - BACKGROUND: TP53 mutation is associated with decreased survival rate in head and
      neck squamous cell carcinoma (HNSCC) patients. We set out to identify microRNAs
      (miRNAs) whose expression associates with TP53 mutation and survival in HNSCC.
      PATIENTS AND METHODS: We analyzed TP53 status by direct sequencing of exons 2
      through 11 of a prospective series of 121 HNSCC samples and assessed its
      association with outcome in 109 followed-up patients. We carried out miRNA
      expression profiling on 121 HNSCC samples and 66 normal counterparts. miRNA
      associations with TP53 mutations and outcome were evaluated. RESULTS: A TP53
      mutation was present in 58% of the tumors and TP53 mutations were significantly
      associated with a shorter recurrence-free survival. This association was stronger
      in the clinical subgroup of patients subjected to adjuvant therapy after surgery.
      The expression of 49 miRNAs was significantly associated with TP53 status. Among
      these 49, we identified a group of 12 miRNAs whose expression correlates with
      recurrence-free survival and a group of 4 miRNAs that correlates with cancer
      specific survival. The two groups share three miRNAs. Importantly, miRNAs that
      correlate with survival are independent prognostic factors either when considered
      individually or as signatures. CONCLUSIONS: miRNAs expression associates with
      TP53 status and with reduced survival after surgical treatment of squamous cell
      carcinoma of the head and neck.

PMID- 24107802
TI  - Hyperbilirubinemia in pazopanib- or sunitinib-treated patients in COMPARZ is
      associated with UGT1A1 polymorphisms.

PMID- 24107803
TI  - High-resolution linkage and quantitative trait locus mapping aided by genome
      survey sequencing: building up an integrative genomic framework for a bivalve
      mollusc.
AB  - Genetic linkage maps are indispensable tools in genetic and genomic studies.
      Recent development of genotyping-by-sequencing (GBS) methods holds great promise
      for constructing high-resolution linkage maps in organisms lacking extensive
      genomic resources. In the present study, linkage mapping was conducted for a
      bivalve mollusc (Chlamys farreri) using a newly developed GBS method-2b
      restriction site-associated DNA (2b-RAD). Genome survey sequencing was performed
      to generate a preliminary reference genome that was utilized to facilitate
      linkage and quantitative trait locus (QTL) mapping in C. farreri. A high
      resolution linkage map was constructed with a marker density (3806) that has, to
      our knowledge, never been achieved in any other molluscs. The linkage map covered
      nearly the whole genome (99.5%) with a resolution of 0.41 cM. QTL mapping and
      association analysis congruously revealed two growth-related QTLs and one
      potential sex-determination region. An important candidate QTL gene named PROP1,
      which functions in the regulation of growth hormone production in vertebrates,
      was identified from the growth-related QTL region detected on the linkage group
      LG3. We demonstrate that this linkage map can serve as an important platform for
      improving genome assembly and unifying multiple genomic resources. Our study,
      therefore, exemplifies how to build up an integrative genomic framework in a non
      model organism. 

PMID- 24107804
TI  - Understanding the sleep-wake cycle: sleep, insomnia, and the orexin system.

PMID- 24107805
TI  - Impact of CYP2D6 and CYP3A4 genetic polymorphism on combined cholinesterase
      inhibitors and memantine treatment in mild to moderate Alzheimer's disease.
AB  - AIM: The impact of CYP2D6 and CYP3A4 polymorphism on the steady-state plasma
      concentrations and therapeutic outcome of donepezil monotherapy and combination
      therapy in Alzheimer's disease (AD) patients. METHODS: A total of 38 patients for
      donepezil and 17 patients for donepezil and memantine therapy, aged >= 55 years,
      were recruited meeting inclusion and exclusion criteria. Polymerase chain
      reaction-restriction fragment length polymorphism was performed. The liquid
      chromatography-tandem mass spectrometry method was used for estimation of drug
      levels of donepezil and memantine. RESULTS: Significant allele frequency was
      observed for CYP2D6*3 polymorphism in patients on donepezil monotherapy and
      combination therapy. Significant allele frequency for CYP2D6*4 was observed in
      the patients on donepezil monotherapy. CONCLUSION: CYP2D6 polymorphism, though
      not significant, might partially be involved in the plasma concentration of AD
      drug.

PMID- 24107806
TI  - Predictive value of maximum standardized uptake value (SUVmax) on 18F-FDG PET/CT
      in patients with locally advanced or metastatic pancreatic cancer.
AB  - PURPOSE: We investigated the prognostic role of 18F-FDG PET/CT in the prediction
      of progression-free survival (PFS) and chemotherapeutic response in patients with
      locally advanced or metastatic pancreatic cancer. METHODS: We enrolled 21 newly
      diagnosed patients with locally advanced or metastatic pancreatic cancer who
      underwent 18F-FDG PET/CT scanning before palliative gemcitabine-based
      chemotherapy between 2006 and 2012. Maximum standardized uptake value (SUVmax) of
      the primary tumor was measured by 18F-FDG PET/CT. Chemotherapeutic response was
      evaluated according to the Response Evaluation Criteria in Solid Tumors. Survival
      analysis was performed for time to progression using the Kaplan-Meier method. Cox
      proportional hazard models were used to determine independent prognostic factors.
      RESULTS: All pancreatic tumors showed detectable FDG uptake (mean SUVmax = 6.8 +/
      3.0, range 2-12) The mean SUVmax values among response groups showed no
      significant difference (P = 0.853) and chemotherapeutic response was not
      different according to SUVmax level (P = 0.807). PFS was significantly shorter in
      the high SUVmax (>=6.8) group than in the low SUVmax (<6.8) group (2.9 vs. 6
      months, P = 0.012). Multivariate analysis revealed that SUVmax was an independent
      prognostic factor for predicting PFS (P = 0.046). CONCLUSIONS: Higher SUVmax of
      primary pancreatic tumor is associated with poor PFS and pretreatment SUVmax is
      an independent prognostic factor for predicting PFS in patients with locally
      advanced or metastatic pancreatic cancer who received gemcitabine-based
      palliative chemotherapy. However, pretreatment SUVmax is not associated with
      chemotherapeutic response.

PMID- 24107807
TI  - Diagnostic and prognostic value of gated SPECT MIBI early post-stress imaging in
      patients with intermediate Duke Treadmill Score.
AB  - PURPOSE OF THE REPORT: The aims of this study were to compare perfusion and
      functional parameters between early (ES) and standard (SS) post-stress gated
      SPECT MIBI, to validate ES against coronary angiography, and to determine whether
      ES parameters can predict future cardiac events. PATIENTS AND METHODS: The sample
      included 63 patients with normal or mildly impaired left ventricular function and
      intermediate Duke Treadmill Score. They underwent a 2-day stress-rest gated SPECT
      MIBI with the post-stress data acquired at 15 minutes (ES) and 60 minutes (SS)
      after i.v. injection of 740 MBq of 99mTc-MIBI. The ES findings were compared to
      SS and against coronary angiography to determine their sensitivity/specificity
      for detecting >70% stenosis. The information about new-onset cardiac events was
      collected 26 +/- 6 months later. RESULTS: Perfusion parameters did not
      significantly differ between ES and SS. Ejection fraction was significantly lower
      and regional wall motion abnormalities were significantly higher on ES than SS.
      The corresponding perfusion and functional parameters were strongly related
      (linear regression slope 0.65-1.00, intercept -0.36-8.5, R2 0.98-0.75). ES
      parameters had high sensitivity (96%) and specificity (83%) for detecting >70%
      stenosis. Lower early stress than rest EF (>5%), higher early stress than rest
      EDV, and early SSS >8 emerged as significant predictors of new-onset cardiac
      events. CONCLUSIONS: Early post-stress gated SPECT MIBI yields comparable
      perfusion and functional parameters as the standard post-stress protocol. ES
      parameters are useful for detecting the existing coronary disease and for
      predicting future cardiac events. ES protocol is recommended for improving
      patient compliance and efficiency of nuclear cardiology services.

PMID- 24107808
TI  - Proposal of a new 18F-FDG PET/CT predictor of response in rectal cancer treated
      by neoadjuvant chemoradiation therapy and comparison with PERCIST criteria.
AB  - PURPOSE: The aim of this study was to correlate PERCIST criteria and a new
      criterion developed in our center that we named PREDIST (PET Residual Disease in
      Solid Tumor) with tumor regression grade (TRG) classification of pathologic
      response to neoadjuvant chemoradiotherapy (CRT) in patients affected by rectal
      cancer. METHODS: Seventy-three consecutive patients affected by locally advanced
      rectal cancer (LARC) were retrospectively included. FDG-PET/CT scans were
      performed at staging time and after the end of CRT (mean time 6.5 weeks). The
      analysis was performed by PERCIST criteria 1.0 and PREDIST criteria based on a
      new definition of residual disease. We split the TRG system into responders (TRG1
      2) and nonresponders (TRG3-5). Pearson chi-square analysis by cross-tabulations
      was performed. RESULTS: PREDIST classification was statistically predictive of
      TRG response (P = 0.004, sensitivity 81.8% and specificity 54.9%). On the
      contrary, PERCIST criteria was not statistically correlated to TRG (P = 0.128)
      caused by a very low specificity (9.8%). CONCLUSIONS: FDG-PET/CT scan is an
      accurate tool to predict preoperatively the response to CRT in LARC patients. The
      novel proposed criterion (PREDIST) seems to be helpful to discriminate responder
      by nonresponder patients.

PMID- 24107809
TI  - A pooled analysis of diagnostic value of 99mTc-ubiquicidin (UBI) scintigraphy in
      detection of an infectious process.

PMID- 24107810
TI  - Intraindividual comparison of 123I-mIBG SPECT/MRI, 123I-mIBG SPECT/CT, and MRI
      for the detection of adrenal pheochromocytoma in patients with elevated urine or
      plasma catecholamines.

PMID- 24107811
TI  - Improved detection of sentinel lymph nodes in SPECT/CT images acquired using a
      low- to medium-energy general-purpose collimator.

PMID- 24107812
TI  - Metastatic ovarian carcinoma showing surprisingly widespread subcutaneous 99mTc
      MDP soft-tissue uptake.
AB  - Cutaneous involvement is generally unusual for metastases in a variety of primary
      malignancies including patients diagnosed with ovarian cancer. We report the rare
      observance of subcutaneous lesions from an aggressive ovarian primary carcinoma
      with unusual uptake of 99mTc-MDP on a tomographic whole-body bone scan without
      osseous metastatic lesions or uptake. The findings were correlated with cross
      sectional imaging in addition to histological analysis.

PMID- 24107814
TI  - Chest wall sarcoma: 18F-FDG PET/CT in a patient with Li-Fraumeni syndrome.
AB  - Li-Fraumeni syndrome is an autosomal dominant inherited disorder also known as
      the SBLA cancer syndrome (sarcoma, breast, leukemia, and adrenal). A 39-year-old
      female patient with a history of bilateral breast cancer treated with bilateral
      mastectomies and radiation treatment 4 years ago and left chest wall pleomorphic
      sarcoma 1 year ago presented with a small hypermetabolic right chest wall mass on
      18F-FDG PET/CT. This mass was found to be a spindle cell sarcoma. FDG PET/CT
      plays an important role in following up oncology patients, particularly in group
      of high-risk malignancy, for detecting small hypermetabolic lesions.

PMID- 24107813
TI  - Tracheal metastasis from melanoma detected with 18F-FDG PET/CT.
AB  - A 58-year-old man with a history of stage IIIB melanoma of the right arm
      initially treated 4 years prior presented with new onset cough and hemoptysis.
      Bronchial washings were positive for melanoma. The PET/CT study showed a
      hypermetabolic nodule in the posterior mid-trachea. These findings indicate
      metastatic melanoma to the trachea. No other metastatic foci were evident. This
      allowed for endoscopic laser ablation of the metastatic focus. 

PMID- 24107815
TI  - False-positive 131I uptake by the temporomandibular joint effusion.
AB  - A 59-year-old man with papillary thyroid carcinoma underwent total thyroidectomy
      and received 2 separate 100-mCi doses of 131I about 5 months apart. A whole-body
      scan 4 days after the second dose revealed a focal uptake in the left
      temporomandibular joint (TMJ). The subsequent MRI examination demonstrated that
      the site of elevated iodine activity was caused by a TMJ effusion.

PMID- 24107816
TI  - FDG-avid venous malformation could mimic malignancy on 18F-FDG PET/CT.
AB  - A 49-year-old female patient with melanoma underwent FDG PET/CT for surveillance.
      PET/CT demonstrated multiple mildly FDG-avid soft tissue attenuation lesions in
      the pelvis of unknown etiology. MRI was performed for further evaluation. MRI
      demonstrated multiple dilated vascular structures measuring up to 2.5 cm
      consistent with venous malformation. Follow-up PET/CT 1 and 2 years later
      demonstrated stable FDG-avid soft-tissue densities in the pelvis representing
      venous malformation. No recurrence or distant metastases were identified. This
      case demonstrates how a benign FDG-avid vascular malformation on PET/CT could
      have been misinterpreted as malignancy. Biopsy of a vascular malformation could
      have had dire consequences. 

PMID- 24107817
TI  - 99mTc-MDP uptake in implantation metastasis of gastric cancer: the additional
      value of SPECT/CT.
AB  - A 47-year-old woman with a history of subtotal gastrectomy due to gastric cancer
      underwent bone scintigraphy to evaluate possible recurrent disease. The whole
      body images revealed a single focus of elevated 99mTc-MDP activity in the right
      pubic region, which was located in the intrapelvic soft tissue on subsequent
      SPECT/CT images. Pathological examination after needle biopsy demonstrated that
      the soft tissue was an implantation metastasis from gastric cancer.

PMID- 24107818
TI  - The placental exposome: placental determinants of fetal adiposity and postnatal
      body composition.
AB  - Offspring of obese and diabetic mothers are at increased risk of being born with
      excess adiposity as a consequence of their intrauterine environment. Excessive
      fetal fat accretion reflects additional placental nutrient transfer, suggesting
      an effect of the maternal environment on placental function. High plasma levels
      of particular nutrients in obese and diabetic mothers are likely to be the
      important drivers of nutrient transfer to the fetus, resulting in excess fat
      accretion. However, not all offspring of obese and diabetic mothers are born
      large for gestational age and the explanation may involve the regulation of
      placental nutrient transfer required for fetal growth. The placenta integrates
      maternal and fetal signals across gestation in order to determine nutrient
      transfer rate. Understanding the nature of these signals and placental responses
      to them is key to understanding the pathology of both fetal growth restriction
      and macrosomia. The overall effects of the maternal environment on the placenta
      are the product of its exposures throughout gestation, the 'placental exposome'.
      Understanding these environmental influences is important as exposures early in
      gestation, for instance causing changes in the function of genes involved in
      nutrient transfer, may determine how the placenta will respond to exposures later
      in gestation, such as to raised maternal plasma glucose or lipid concentrations.
      Longitudinal studies are required which allow investigation of the influences on
      the placenta across gestation. These studies need to make full use of developing
      technologies characterising placental function, fetal growth and body
      composition. Understanding these processes will assist in the development of
      preventive strategies and treatments to optimise prenatal growth in those
      pregnancies at risk of either excess or insufficient nutrient supply and could
      also reduce the risk of chronic disease in later life.

PMID- 24107819
TI  - [Participation rates in the third round (2006-2007) of the breast cancer
      screening program in Hungary].
AB  - Organised, nationwide screening for breast cancer with mammography in the age
      group of 45-65 years with 2 years screening interval started in Hungary in
      January 2002. The aim of this study is to analyse the attendance rate of breast
      screening programme for the 2006/2007 years, including the analysis of the ratio
      of screening and diagnostic mammography examinations. The data derive from the
      financial database of the National Health Insurance Fund Administration (NHIFA)
      covering the 8 years period between 2000 and 2007. The ratio of women in the age
      group of 45-65 years was calculated having either a screening mammography or a
      diagnostic mammography. The analysis was carried out for the years 2000-2001
      before and 2006-2007 after the implementation of nationwide organised programme.
      In the years 2000-2001 7.26% of the women aged 45-65 years had an opportunistic
      screening mammography while in 2006-2007 29.4% of the target population had
      screening mammography within the organised programme. During the same periods
      19.8% (2000-2001) and 21.8% (2006-2007) of women aged 45-65 years had a
      diagnostic mammography. Thus the total (screening and diagnostic) coverage of
      mammography increased from 26.2% (2000-2001) to 49.7% (2006-2007). The attendance
      of the Hungarian organised breast cancer screening programme slightly declined in
      2006-2007 compared to 2002-2003/2004-2005, and to achieve the expected results in
      mortality decrease a further improvement of the uptake is necessary. 

PMID- 24107820
TI  - [HER2-positive breast cancer: available targeted agents and biomarkers for
      therapy response].
AB  - In the last decade, the targeted therapy of breast cancer became part of routine
      clinical protocols all over the globe. Options in today's targeted therapy
      include hormonal therapy and the modulation of the EGFR/HER-pathway. Of the four
      HER receptors, HER2 is the target of currently used treatment strategies. HER2
      activates multiple intracellular pathways via RAS, RAF and PI3K. We give a
      comprehensive summary of approved monoclonal antibodies and tyrosine kinase
      inhibitors acting over HER2, including trastuzumab, lapatinib and pertuzumab. We
      elaborate on their mechanism of action and on clinical trials behind their
      approval. Agents in third phase clinical studies (neratinib, afatinib) are also
      described. We give a brief overview of agents currently in phase I and phase II
      studies; these are acting over the PI3K pathway, over IGFR1 and over HSP90.
      Furthermore, currently validated negative biomarkers (markers predicting lack of
      response) in clinical use are also summarized. Finally, the major bottlenecks of
      clinical application including tumor heterogeneity and the high diversity of
      clinical studies are discussed. For a breakthrough we will need to identify new
      positive biomarkers of therapy response. 

PMID- 24107822
TI  - [The prognostic role of age in oral cancer. A clinical study].
AB  - The problem of malignant tumors developing in a young age is a topic of special
      importance and subject of intensive research. The occurrence of oral cavity
      tumors shows a decreasing trend worldwide, while the incidences of oral squamous
      cell carcinoma diagnosed at young adulthood is increasing. The etiology of tumors
      developing in young age is not yet fully understood, however, it can be stated
      that the usual high-risk behavioral patterns (i.e. smoking and alcohol abuse)
      play only a minor role in this patient group, if any. Our own observations
      indicate a higher regional and locoregional relapse for these patients and,
      although they turn for help early, at an early stage of the disease, a lower
      chance of survival. The target of our research was to analyze the differences in
      certain etiological, pathological and clinical parameters of our own patient
      group consisting of both young and older patients. The data of 105 young (<50
      years) and, as a control group, 105 older (>50 years) patients were analyzed. The
      patients have undergone surgery and, if necessary, radiotherapy and/or
      chemotherapy. The tumor-specific survival was determined at 36 months. Our study
      aimed at understanding the relationship between the clinical prognostic factors
      (stage, localization, anamnestic time), smoking habits, gender and age of the
      patients. Relationship between cancer occurrence (local, locoregional relapse)
      and survival rate, as well as age and survival rate were analyzed. We found that
      young patients report themselves for treatment at an early stage. Smoking and
      alcohol abuse were considerably less. When a relapse occurs, it occurs more
      frequently and earlier than at older patients. The most decisive correlation was
      observed between age and anamnestic time, age and number of cigarettes smoked,
      age and time elapsed until relapse, as well as age and cancer-specific survival.
      Moreover, cancer-specific survival of patients younger than 50 years of age was
      found significantly shorter than in the control group. 

PMID- 24107821
TI  - [Monoclonal antibody therapy in breast cancer].
AB  - A new trend has been taking place in the daily oncology practice in the past
      twenty years: we are progressively moving toward individualized and personalized
      treatments. The treatment of breast cancer is one of the best examples to
      underline the outstanding effectiveness of the individualized approach. The
      modern molecular pathology features are capable of predicting the biological
      behavior of the tumors which gives a new basis for our therapeutic choices, both
      for neoadjuvant and adjuvant settings, as well as for metastatic disease. In our
      paper we review the currently used monoclonal antibodies in the treatment of
      breast cancer and provide an overview of the new research and future directions
      in this field.

PMID- 24107823
TI  - [First Hungarian experience with pazopanib therapy for patients with metastatic
      renal cancer].
AB  - Pazopanib, a tyrosine kinase inhibitor, is one of the new registered first-line
      therapeutic options in the treatment of metastatic clear cell renal carcinoma.
      Our aim was to evaluate the efficiency and toxicity of first-line pazopanib
      therapy administered for patients with metastatic clear cell renal carcinoma with
      good- and medium prognosis according to MSKCC criteria. Between January and May,
      2011, 24 patients have been treated with pazopanib in 8 oncology centers in
      Hungary, out of them 21 patients' data were analyzed. The mean age was 65.3 (49
      81) years, 10 males and 11 females. According to MSKCC the prognosis was good and
      medium in 3 and 18 cases, respectively. Daily dose of pazopanib was 800 mg
      administered continuously in 28 day cycles. Dose reduction was performed
      according to the instructions of the registration study. Tumor response was
      evaluated according to RECIST 1.0. Currently 6 (28.6%) patients are on treatment.
      Dose reduction was necessary in 6 (28.6%) cases with an average duration of 14.55
      (7-150) days. Mean+/-SE daily dose was 692.97+/-13.67 (400-800) mg. Median PFS
      was 12.41 months (95% CI 11.52-12.94 months). Complete remission (CR), as the
      best tumor response occurred in 2 (9.5%) cases. Partial remission (PR), stable
      disease (SD) and progression was observed in 6 (28.6%), 10 (47.6%) and 3 (14.3%)
      cases, respectively. Objective tumor response was observed in 8 pts (38%). Median
      survival could not be statistically analyzed yet due to the insignificant number
      of fatal outcomes. Median follow-up was 25.22 months (95% CI 2.47-28.1 months).
      As common side-effect fatigue, weakness and diarrhea occurred in 11 (52.4%), 9
      (42.9%) and 8 (38%) cases, respectively. Besides these, worsening of high blood
      pressure and ALT/AST elevation was observed in 5 (23.8%) and 6 (28.6%) cases,
      respectively. Based on the initial Hungarian experiences, pazopanib is a well
      tolerable product and can be administered safely. According to our results its
      efficiency in terms of tumor response and progression-free survival is comparable
      to the results of the registration study. 

PMID- 24107824
TI  - [Diabetes in patients with malignant tumors].
AB  - Disturbances of the carbohydrate metabolism are fairly common is patients with
      malignancy. On the other hand, diabetes appears to have an effect on the
      development and progression of various tumors. Malignant diseases and the
      therapies used in their treatment often have an impact on carbohydrate
      metabolism, while diabetes may hinder specific oncotherapy or influence
      oncological therapeutic decisions. Several complications of malignant diseases
      and some of the medications used in their treatment, such as steroids or
      parenteral nutrition, may raise blood glucose levels. The various obstacles of
      oral nutrition frequently seen in patients with malignancy can lead to
      hypoglycaemia in patients with diabetes. Our article endeavours to review the
      pathophysiological and clinical connection between diabetes and malignant
      diseases and the use of insulin, oral antidiabetic drugs and diet in patients
      with malignant disease. 

PMID- 24107825
TI  - [Role and responsibility of multimodal imaging in head and neck cancer].
AB  - Hungary is first in head and neck cancer mortality in Europe in men and also in
      women. Head and neck (HN) is a difficult region, its anatomy and also pathology
      is very complex, various connection points exist between the sites which
      determine the extension of the disease. Diagnostic algorithms as well as imaging
      techniques have to be optimized to examine in standard manner. Like most other
      cancers, prognosis depends largely on the stage of the tumor. Accuracy of tumor
      detection and evaluation is very important because it affects treatment planning.
      As non-surgical organ-preserving therapeutic modalities (chemotherapy,
      chemoradiotherapy, targeted biological therapy) gain general acceptance, the
      importance of noninvasive diagnostic accuracy as well as radiologic evaluation of
      the extent of the tumor has increased. Clinical examinations including endoscopy
      should be combined with radiologic imaging to assess the precise local (T),
      regional nodal (N), and distant (M) extent of the tumor. Computed tomography (CT)
      and magnetic resonance imaging (MRI) have become basic tools in the diagnosis of
      head and neck tumors. They are both useful for assessing deep tumor extensions,
      able to detect changes missed by endoscopy. It has been shown that the primary
      determined tumor stage increases in up to 90% of patients after the results of
      cross sectional imaging. MRI is being increasingly used and has become the gold
      standard in head and neck cancer for staging, assessing tumor response, finding
      recurrent tumor and also for treatment planning in radiotherapy. The field
      strength of MRI scanners has been increasing to 1.5 T and now 3 T with better
      signal-to-noise ratio, higher resolution images and better tissue diagnosis.
      Functional MR techniques such as dynamic contrast enhanced MRI (DCE-MRI) and
      diffusion weighted MRI (DW-MRI) may provide further characterization. PET/CT is
      beneficial in detecting unsuspected metastatic nodes, distant disease and second
      primary tumor. PET/CT and MRI both appeared almost similarly accurate in the
      detection of an occult primary tumor. The effective management of patients
      depends highly on the competece of radiologists and requires close collaboration
      between clinical and surgical oncologists, diagnostic and therapeutic
      radiologists as well as pathologists. 

PMID- 24107826
TI  - [Endometrial cancer in young patients: report of 17 cases].
AB  - Endometrial cancer of young (less then 40 years old) patients comprises 4-5% of
      all endometrial cancers in Hungary. The majority of patients did not give birth
      yet, so fertility sparing is very important. Fertility sparing treatment is
      possible if the tumor's histology is endometrial type and Grade 1 (well
      differentiated). The tumor localizes only to the endometrium and there is no
      myometrium infiltration. The authors present 17 cases of patients treated at the
      Department of Gynecology of National Institute of Oncology (Budapest, Hungary).
      In 3 cases conservative therapy (progesterone treatment) was possible, and 14
      patients had to undergo surgery, because conservative treatment did fail. Of 17
      patients 14 were never pregnant. The average patient's age was 32.35 +/- 4.27
      years. The mean body weight was 93.13 +/- 30.79 kg (from 58 kg up to 147 kg); in
      7 cases BMI (body mass index) was more than 30. After surgery histological
      examination had revealed 2 cases with normal ovaries, 1 case of simple cyst and 1
      case of malignant ovarian tumor (serous adenocarcinoma, Grade 2), and 10 cases of
      polycystic ovaries associated with endometrial cancer. Of 3 cases that had only
      curettage, the endometrial cancer was Grade 1, and in 1 case radiological imaging
      showed simplex ovarian cyst. The authors' findings concerning young endometrial
      cancer patients confirm the results published in the literature. In cases
      suitable for fertility sparing treatment it is not sufficient to concentrate only
      on endometrial findings, but is very important to focus on the therapy of cystic
      ovaries (80% of which is PCO), obesity and diabetes mellitus as well. 

PMID- 24107827
TI  - [Appendiceal mucocele as differential diagnostic problem of palpable mass in the
      right lower abdominal region].
AB  - Appendiceal mucocele is a rare disease (0.2-0.3% of all appendectomies) and it is
      defined as abnormal accumulation of mucoid material in the appendiceal lumen.
      Almost half of the patients are asymptomatic. The most common clinical
      manifestation is pain and palpable mass in the right iliac fossa, which is
      difficult to differentiate from the malignant or benign adnexal masses. By
      presenting our three cases, we would like to draw attention to the diagnostic
      difficulties of the pain and palpable mass in the right lower abdominal region. 

PMID- 24107829
TI  - Parental experience of end-of life care in the pediatric intensive care unit.
AB  - BACKGROUND: There is a considerable variability among European countries
      regarding the management of end-of-life (EOL) care in the pediatric critical care
      setting. In Italy, recommendations on these issues are available but no study has
      investigated the parents' experience. The aim of this study was to explore
      parents' experience of EOL care in a Pediatric Intensive Care Unit (PICU) in
      Italy. METHODS: The study was conducted in a 6-bed PICU of a university
      affiliated hospital in Milan. Parents of children who died between 2007-2010
      after a stay of at least 24 hours were eligible to participate. Through semi
      structured interviews, parents were asked to describe the story of their child's
      stay in the PICU, including his/her final moments. The interviews were audio
      recorded, transcribed verbatim and analyzed according to the hermeneutic
      phenomenology approach. RESULTS: Twelve parents of 8 children were interviewed.
      Four themes emerged that described the parents' experience: 1) loss of parental
      role; 2) lack of physical intimacy with their child; 3) ambivalence about end-of
      life decisions; and 4) reclaiming the dying process. CONCLUSION: Our findings
      suggest that in order to improve pediatric EOL care we need to better integrate
      medical and parental priorities, in a shared process that allows parents to
      preserve their role and relationship with their child. The most critical aspect
      for parents was not related to the involvement (or not) in EOL decisions, but
      rather to the possibility of staying connected with their child during the
      hospitalization and at the time of death.

PMID- 24107828
TI  - A key role for EZH2 in epigenetic silencing of HOX genes in mantle cell lymphoma.
AB  - The chromatin modifier EZH2 is overexpressed and associated with inferior outcome
      in mantle cell lymphoma (MCL). Recently, we demonstrated preferential DNA
      methylation of HOX genes in MCL compared with chronic lymphocytic leukemia (CLL),
      despite these genes not being expressed in either entity. Since EZH2 has been
      shown to regulate HOX gene expression, to gain further insight into its possible
      role in differential silencing of HOX genes in MCL vs. CLL, we performed detailed
      epigenetic characterization using representative cell lines and primary samples.
      We observed significant overexpression of EZH2 in MCL vs. CLL. Chromatin immune
      precipitation (ChIP) assays revealed that EZH2 catalyzed repressive H3 lysine 27
      trimethylation (H3K27me3), which was sufficient to silence HOX genes in CLL,
      whereas in MCL H3K27me3 is accompanied by DNA methylation for a more stable
      repression. More importantly, hypermethylation of the HOX genes in MCL resulted
      from EZH2 overexpression and subsequent recruitment of the DNA methylation
      machinery onto HOX gene promoters. The importance of EZH2 upregulation in this
      process was further underscored by siRNA transfection and EZH2 inhibitor
      experiments. Altogether, these observations implicate EZH2 in the long-term
      silencing of HOX genes in MCL, and allude to its potential as a therapeutic
      target with clinical impact. 

PMID- 24107830
TI  - Inhaled antibiotics in mechanically ventilated patients.
AB  - During the last decade, inhaled antibiotics, especially colistin, has been widely
      used worldwide as a therapeutic option, supplementary to conventional intravenous
      antibiotics, for the treatment of multidrug-resistant (MDR) Gram-negative
      nosocomial and ventilator-associated pneumonia (VAP). Antimicrobial aerosols are
      commonly used in mechanically ventilated patients with VAP, although information
      regarding their efficacy and optimal technique of administration has been
      limited. Recent studies showed that the administration of inhaled antibiotics in
      addition to systemic antibiotics provided encouraging results associated with low
      toxicity for the management of VAP mainly due to MDR Gram negative bacteria.
      Although the theory behind aerosolized administration of antibiotics seems to be
      sound, there are limited data available to support the routine use of this
      modality since very few randomized controlled trials (RCTs) have still examined
      the efficacy of this approach in patients with VAP. Additionally, this route of
      antibiotic delivery has not been approved until now neither by the FDA nor by the
      European Medicines Agency (EMEA) in patients with VAP. However, since the problem
      of VAP due to MDR bacteria has been increased worldwide RCTs are urgently needed
      in order to prove the safety, efficiency and efficacy of inhaled antimicrobial
      agents administered alone or in conjunction with parenteral antibiotics for the
      management of VAP in critically ill patients. Indeed, more data are needed to
      establish the appropriate role of inhaled antibiotics for the treatment of VAP. 

PMID- 24107831
TI  - Comparison of the efficacy of different concentrations and volumes of
      levobupivacaine in axillary brachial plexus blockade.
AB  - BACKGROUND: The aim of this study was to compare the effect of the same dosage
      but different concentrations and volumes of levobupivacaine used for axillary
      block on the onset and intensity of the block. METHODS: Sixty-nine patients were
      randomly allocated into three groups. The patients in Group 5, Group 7.5 and
      Group 3.75 were administered 45 mL of levobupivacaine (5 mg/mL), 30 mL of
      levobupivacaine (7.5 mg/mL) and 30 mL of levobupivacaine (7.5 mg/mL) mixed with
      30 mL of 0.9% NaCl solution, respectively. The onset and intensity of sensory and
      motor blocks distributed through 4 nerves, duration of analgesia, and total
      analgesic consumption within 24 hr were recorded. RESULTS: Onset of sensory block
      on median and radial nerves in Group 3.75 was found to be significantly longer
      compared to Group 5 and Group 7.5 (P<0.05). Onset of motor block on radial nerves
      in cases in Group 3.75 was significantly longer compared to those in Group 7.5
      (P<0.01). In Group 3.75 the intensity of sensorial blockade at the median ulnar
      and radial nerves and the intensity of motor blockade at the radial and
      musculocutaneous nerves were significantly lower than in the other two groups.
      The duration of analgesia in the patients of Group 5 was significantly shorter
      compared to those in Groups 7.5 and 3.75 (P<0.01). CONCLUSION: Decreasing the
      concentration and increasing the volume of levobupivacaine without changing its
      dosage prolongs the duration of analgesia, although it delays the onset and
      decreases the intensity of sensory and motor block in axillary block.

PMID- 24107832
TI  - Accuracy of leptin serum level in diagnosing ventilator-associated pneumonia: a
      case-control study.
AB  - BACKGROUND: Undernutrition causes a reduction of body-fat mass and a decrease in
      the circulating concentration of leptin which impairs the production of
      proinflammatory cytokines and increases the incidence of infectious diseases. The
      main objective of this study was to determine whether leptin deficiency is a risk
      factor for ventilator-associated pneumonia (VAP). METHODS: This prospective
      observational case-control study was conducted in a university ICU during a 2
      year period. Patients with VAP (cases) were matched (1:1) to patients without VAP
      (controls) according to all the following criteria: age, gender, SAPS II, and
      duration of ICU stay before VAP occurrence. In all patients leptin, C-reactive
      protein (CRP) and procalcitonin (PCT) were measured at ICU admission, and twice a
      week. In addition, in cases, leptin, CRP and PCT were also measured on the day of
      VAP diagnosis. RESULTS: Eighty-six cases were matched with 86 controls. No
      significant difference was found in leptin and PCT levels between cases and
      controls. CRP level was significantly higher on the day of VAP in cases compared
      with controls (99 vs. 48 mg/L, P=0.001). Combination of CRP-leptin (CRP >=78 mg/L
      and leptin >=6.2 ng/mL on the day of VAP) was significantly (P=0.009) associated
      with VAP in univariate analysis. Multivariate analysis identified the combination
      of CRP-leptin (OR [95% CI] 3.08 [1.18-8.04], P=0.003), LOD score (1.27 [1.08
      1.48], P=0.003), neuromuscular-blockers use (6.6 [2.03-21.7], P=0.002), and
      reintubation (3.3 [1.14-9.6], P=0.027) as independent risk factors for VAP.
      CONCLUSION: In our study, leptin level was not associated with VAP occurrence.
      Further studies are needed to confirm our results, and to define the exact
      inflammatory role of leptin, and its interest as a biomarker in ICU patients.

PMID- 24107834
TI  - Mechanical circulatory support for acute heart failure in 2013: an update on
      available devices, indications and results.
AB  - Severe acute heart failure often requires some form of mechanical support to
      circulation. The use of intraaortic balloon counterpulsation in postinfarction
      cardiogenic shock - perhaps the most common scenario of this kind - has been
      recently questioned in the IABP SHOCK trial. In the most severe forms,
      extracorporeal membrane oxygenation is becoming the mainstay of treatment to
      support circulation or in order to gain time for a further evaluation. Moreover,
      advances in technology and a reducing number of donors are leading to more
      extended indications to the implantation of ventricular assist devices. Herein,
      we offer a focused review on recent articles dealing with mechanical support to
      circulation in acute heart failure, which we found relevant in terms of their
      possible impact on therapeutic strategies and indication.

PMID- 24107833
TI  - Management program decreases postoperative nausea and vomiting in high-risk and
      in general surgical patients: a quality improvement cycle.
AB  - BACKGROUND: Preventing postoperative nausea and vomiting (PONV) is a major
      priority for postsurgical patient care. Our objective was to assess the efficacy
      of a multimodal postoperative nausea and vomiting (PONV) approach, which was
      associated with a continuous quality improvement program, in maintaining a low
      PONV incidence in the PACU. METHODS: Consecutive adult patients scheduled for
      surgery (ambulatory surgery or not) were prospectively included. PONV data were
      recorded in the PACU and over a 24-hour period. The management program was based
      on a multimodal approach with both changes in anesthetic techniques and anti
      emetics, and on a three-stage protocol including: 1) phase I: institutional
      practice phase based on prospective observational study; 2) protocol
      implementation; 3) phase II: prospective observational study associated with
      feedback, scientific session and evaluation to guideline adherence. We used the
      Apfel risk scoring system to identify patients at high risk of PONV. Feedback
      with audit results and didactic sessions were scheduled quarterly in the Phase
      II. RESULTS: Thirty-seven/395 (9.4%) and 151/3864 (3.9%) patients experienced
      PONV in the PACU during Phase I and Phase II respectively (P<0.001). Among the
      patients with an Apfel risk score that included at least two risk factors, 16.6%
      and 4.2% experienced PONV in the PACU during Phase I and Phase II respectively
      (P<0.001). CONCLUSION: We highlight the association with a sharp decrease in PONV
      incidence over a one-year period and a multimodal PONV approach using feedback to
      clinicians associated with continuous quality improvement program.

PMID- 24107835
TI  - Oxygen saturation in central venous blood: does the site of measurement matter?

PMID- 24107836
TI  - Diaphragmatic dysfunction after laparoscopic radical prostatectomy: effect of
      anesthetic technique and applicability of ultrasonography for evaluation.

PMID- 24107837
TI  - Videolaryngoscopy--is there a role in paediatric airway management?

PMID- 24107838
TI  - The luxury of breathing oxygen.

PMID- 24107839
TI  - Upregulation of TRPC1 contributes to contractile function in isoproterenol
      induced hypertrophic myocardium of rat.
AB  - AIMS: The transient receptor potential canonical channel 1 (TRPC1) is a crucial
      component of the stretch-activated ion channels (SACs). The objective of this
      research was to demonstrate the contribution of TRPC1 in maintaining cardiac
      contractile function in the hypertrophic myocardium. METHODS: Hypertrophic rat
      hearts were induced by injecting isoproterenol intraperitoneally, and the
      expressions of TRPC1/3/6 and Na(+)/Ca(2+) exchanger 1 (NCX1) proteins were
      analyzed by Western blot. The intracellular calcium images, the action potential
      of myocardium, the length-dependent contractile force of ventricle muscle and the
      cardiac output of isolated heart were investigated. RESULTS: The expression of
      TRPC1 was increased in the hypertrophic myocardium. After being stretched, the
      ascendant amplitude of the increase in the intracellular calcium ion
      concentration ([Ca(2+)]i) in the hypertrophic myocardium was higher than that in
      the normal myocardium. The increase of the APD50 and the amplitude of the
      membrane potential depolarization were more significant in the hypertrophic
      myocardium after the activation of SACs. When the heart preparations were
      perfused with Tyrode's solution, there was no difference in the cardiac systolic
      function between the cardiac hypertrophy group and the control group. Gadolinium,
      a SACs blocker, reduced the length-dependent contractile force and suppressed the
      ascending limb of the Frank-Starling curves in the hypertrophic heart.
      CONCLUSIONS: The upregulation of TRPC1 contributes to the contractile function in
      the hypertrophic myocardium by increasing [Ca(2+)]i through the SACs.

PMID- 24107840
TI  - Integrated spatial multiplexing of heralded single-photon sources.
AB  - The non-deterministic nature of photon sources is a key limitation for single
      photon quantum processors. Spatial multiplexing overcomes this by enhancing the
      heralded single-photon yield without enhancing the output noise. Here the
      intrinsic statistical limit of an individual source is surpassed by spatially
      multiplexing two monolithic silicon-based correlated photon pair sources in the
      telecommunications band, demonstrating a 62.4% increase in the heralded single
      photon output without an increase in unwanted multipair generation. We further
      demonstrate the scalability of this scheme by multiplexing photons generated in
      two waveguides pumped via an integrated coupler with a 63.1% increase in the
      heralded photon rate. This demonstration paves the way for a scalable
      architecture for multiplexing many photon sources in a compact integrated
      platform and achieving efficient two-photon interference, required at the core of
      optical quantum computing and quantum communication protocols. 

PMID- 24107841
TI  - Subjective experience of thought overactivation in mood disorders: beyond racing
      and crowded thoughts.
AB  - BACKGROUND: Racing thoughts, crowded thoughts and flight of ideas are frequent
      symptoms in mood disorders, but the underlying subjective experience of
      overactivation of thought processes remains poorly documented. METHODS:
      Qualitative analysis of audiotaped interviews explored subjective experience of
      thought overactivation in patients with mood disorders (sample 1, n = 45).
      Quantitative analysis considered the properties of a newly developed rating scale
      in sample 1, in an additional sample of patients with mood disorders (sample 2, n
      = 37) and in healthy subjects (sample 3, n = 38). RESULTS: Qualitative analysis
      of individual interviews revealed that 5 conceptual categories characterized
      thought overactivation: sequential thought flow, overstimulation, competition for
      resource allocation, unexpected/unexplained onset, and association with mood and
      emotions. A principal component analysis of the initial 16-item rating scale
      indicated that a single component explained 55.9% of the variance, with major and
      exclusive contributions from 9 items, which were retained in the final 9-item
      Subjective Thought Overactivation Questionnaire (STOQ; Cronbach's alpha = 0.95).
      Total score correlated significantly with activation, depression and perceived
      conflict subscales of the Internal State Scale (ISS; rs = 0.57-0.66, p < 0.001).
      It was associated with decreased well-being (ISS; rs = -0.48, p = 0.001) and
      increased state anxiety (State-Trait Anxiety Inventory; rs = 0.60, p < 0.001).
      The STOQ score was significantly higher in patients than in healthy subjects. It
      allowed distinguishing between ISS mood states, with the highest median score in
      mixed states. LIMITATIONS: Sample size, representativeness, possible bias in
      qualitative analysis, and quality of expert consensus. CONCLUSIONS: Qualitative
      analysis of clinical interviews, together with a new short rating scale,
      contributed to a documentation of subjective thought overactivation, an important
      but often undetected feature in mood disorders.

PMID- 24107842
TI  - Stigmatisation of a formerly obese young female.
AB  - BACKGROUND: Weight loss does not necessarily decrease the negative appraisal of a
      formerly overweight individual. Since past weight history tends to be disclosed
      in several contexts, this study aims to investigate whether negative appraisals
      are gender-specific and if they are modulated by the evaluators' own BMI.
      METHODS: 202 young adults (106 male and 96 female) viewed a picture of a young
      attractive female (target) accompanied by one of two statements about her past
      weight (overweight (OW) or always kept a normal weight (NW)), and then rated her
      using the Fat Phobia Scale (FPS). RESULTS: Female evaluators rated the target
      with the OW statement more negatively than the target with the NW statement. In
      contrast, males exposed to the OW statement rated the target as having fewer
      emotional/psychological problems and being less stupid/uncreative. BMI only
      influenced ratings in males, where those with higher BMI ascribed more negative
      attributes to the target with the NW statement than the OW statement. CONCLUSION:
      Information on weight history impacts upon the appraisal of peers. These effects
      are dependent on gender and BMI. Knowing that a young female was overweight
      triggered negative evaluations from females but did not appear to impact the
      judgment of males.

PMID- 24107843
TI  - Abstracts of the 11th International Symposium on Mechanisms of Vasodilatation.
      Zurich, Switzerland. October 4-6, 2013.

PMID- 24107844
TI  - Rapamycin induces ILT3(high)ILT4(high) dendritic cells promoting a new
      immunoregulatory pathway.
AB  - ILT3(high)ILT4(high) dendritic cells (DCs) may cause anergy in
      CD4(+)CD45RO(+)CD25(+) T cells transforming them into regulatory T cells (Tregs).
      Here, we tested whether chronic exposure to rapamycin may modulate this
      immunoregulatory pathway in renal transplant recipients. Forty renal transplant
      patients with biopsy-proven chronic allograft nephropathy and receiving
      calcineurin inhibitors were randomly assigned to either calcineurin inhibitor
      dose reduction or withdrawal with rapamycin introduction. At conversion and 2
      years thereafter, we measured the rapamycin effects on circulating DCs
      (BDCA1/BDCA2 and ILT3/ILT4 expression), CD4(+)/CD25(high)/Foxp3(+) Tregs,
      CD8(+)/CD28(-) T cells, and the Th1/Th2 balance in graft biopsies. In rapamycin
      treated patients, peripheral BDCA2(+) cells were significantly increased along
      with ILT3/ILT4(+) DCs. The number of circulating
      CD4(+)/CD25(high)/Foxp3(+)/CTLA4(+) Tregs, CD8(+)CD28(-) T cells, and HLA-G serum
      levels were higher in the rapamycin-treated group. The number of
      ILT3/ILT4(+)BDCA2(+) DC was directly and significantly correlated with
      circulating Tregs and CD8(+)CD28(-) T cells. ILT3/ILT4 expression was increased
      in kidney biopsies at the end of the study period along with a significant bias
      toward a Th2 response within the graft only in the rapamycin-treated patients.
      Thus, rapamycin induces the upregulation of ILT3 and ILT4 on the DC surface, and
      this effect is associated with an increase in the number of Tregs and expansion
      of the CD8(+)CD28(-) T cell population. This suggests that mTOR inhibition may
      promote a novel immunoregulatory pathway. 

PMID- 24107845
TI  - Kidney function and the risk of cardiovascular disease in patients with type 2
      diabetes.
AB  - The association of estimated glomerular filtration rate (GFR) with cardiovascular
      disease risk among patients with type 2 diabetes is unclear. Here we
      prospectively investigated the race-specific association of estimated GFR with
      the risk of coronary heart disease and stroke among 11,940 Caucasian and 16,451
      African-American patients. During mean follow-up of 6.1-6.8 years, 6647 coronary
      heart disease and 2750 stroke incident cases were identified. Age- and sex
      adjusted hazard ratios of coronary heart disease associated with baseline
      estimated GFR (90 or more, 75-89, 60-74, 30-59, and 15-29 ml/min per 1.73 m2)
      were 1.00, 1.04, 1.13, 1.37, and 2.07 (significant trend) for African Americans,
      and 1.00, 1.09, 1.10, 1.31, and 2.18 (significant trend) for Caucasians,
      respectively. A significantly increased stroke risk was observed among both
      African-American and Caucasian participants with an estimated GFR under 60 ml/min
      per 1.73 m2. When using the updated mean values of estimated GFR, these
      significant associations became stronger. Participants with mildly decreased
      estimated GFR (60-89 ml/min per 1.73 m2) during follow-up were also at a
      significantly higher risk of coronary heart disease and stroke. Thus, even mildly
      reduced estimated GFR at baseline (under 75 ml/min per 1.73 m2) and during follow
      up (under 90 ml/min per 1.73 m2) increased the risk of incident coronary heart
      disease and stroke among both African-American and Caucasian type 2 diabetes
      patients.

PMID- 24107846
TI  - Phosphate restriction significantly reduces mortality in uremic rats with
      established vascular calcification.
AB  - The role of hyperphosphatemia in the pathogenesis of secondary
      hyperparathyroidism, cardiovascular disease, and progression of renal failure is
      widely known. Here we studied effects of dietary phosphate restriction on
      mortality and vascular calcification in uremic rats. Control and uremic rats were
      fed a high-phosphate diet and at 3 months a portion of rats of each group were
      killed. Serum phosphate and the calcium phosphate product increased in uremic
      rats, as did aortic calcium. Of the rats, 56% had positive aortic staining for
      calcium (von Kossa), RUNX2, and osteopontin. The remaining uremic rats were
      continued on diets containing high phosphate without and with sevelamer, or low
      phosphate, and after 3 more months they were killed. Serum phosphate was highest
      in uremic rats on high phosphate. Serum PTH and FGF-23 were markedly lower in
      rats on low phosphate. Mortality on high phosphate was 71.4%, with sevelamer
      reducing this to 37.5% and phosphate restriction to 5.9%. Positive aortic
      staining for von Kossa, RUNX2, and osteopontin was increased, but phosphate
      restriction inhibited this. Kidneys from low-phosphate and sevelamer-treated
      uremic rats had less interstitial fibrosis, glomerulosclerosis, and inflammation
      than those of uremic rats on high phosphate. Importantly, kidneys from rats on
      low phosphate showed improvement over kidneys from high-phosphate rats at 3
      months. Left ventricles from rats on low phosphate had less perivascular fibrosis
      and smaller cardiomyocyte size compared to rats on high phosphate. Thus,
      intensive phosphate restriction significantly reduces mortality in uremic rats
      with severe vascular calcification. 

PMID- 24107848
TI  - Epidemiology, impact, and treatment options of restless legs syndrome in end
      stage renal disease patients: an evidence-based review.
AB  - Restless legs syndrome (RLS) (or Willis-Ekbom disease) is a neurological disorder
      with high prevalence among the end-stage renal disease population. This is one of
      the most predominant types of secondary RLS, and it is called uremic RLS. Despite
      the fact that uremic RLS has been less studied compared to idiopathic RLS, recent
      studies now shed light in many aspects of the syndrome including clinical
      characteristics, impact, epidemiology, and treatment options. The current review
      discusses the above topics with special emphasis given on the management of
      uremic RLS, including the management of symptoms that often appear during a
      hemodialysis session. Uremic RLS symptoms may be ameliorated by using
      pharmacological and nonpharmacological treatments. Evidence so far shows that
      both approaches may be effective in terms of reducing the RLS symptom's severity;
      nevertheless, more research is needed on the efficiency of treatments for uremic
      RLS. 

PMID- 24107847
TI  - An endogenous ribonuclease inhibitor regulates the antimicrobial activity of
      ribonuclease 7 in the human urinary tract.
AB  - Recent studies stress the importance of antimicrobial peptides in protecting the
      urinary tract from infection. Previously, we have shown that ribonuclease 7
      (RNase 7) is a potent antimicrobial peptide that has a broad-spectrum
      antimicrobial activity against uropathogenic bacteria. The urothelium of the
      lower urinary tract and intercalated cells of the kidney produce RNase 7, but
      regulation of its antimicrobial activity has not been well defined. Here, we
      characterize the expression of an endogenous inhibitor, ribonuclease inhibitor
      (RI), in the urinary tract and evaluate its effect on the antimicrobial activity
      of RNase 7. Using RNA isolated from non-infected human bladder and kidney tissue,
      quantitative real-time polymerase chain reaction showed that RNH1, the gene
      encoding RI, is constitutively expressed throughout the urinary tract. With
      pyelonephritis, RNH1 expression and RI peptide production significantly decrease.
      Immunostaining localized RI production to the umbrella cells of the bladder and
      intercalated cells of the renal collecting tubule. In vitro assays showed that RI
      bound to RNase 7 and suppressed its antimicrobial activity by blocking its
      ability to bind the cell wall of uropathogenic bacteria. Thus, these results
      demonstrate a new immunomodulatory role for RI and identified a unique regulatory
      pathway that may affect how RNase 7 maintains urinary tract sterility. 

PMID- 24107849
TI  - IgG4-related kidney disease.
AB  - IgG4-related kidney disease (IgG4-RKD) is a comprehensive term for renal lesions
      associated with IgG4-related disease, which is a recently recognized clinical
      entity characterized by a dense lymphoplasmacytic infiltrate rich in IgG4
      positive plasma cells with fibrosis affecting several organs. Tubulointerstitial
      nephritis with increased IgG4-positive plasma cells and fibrosis is the most
      dominant feature of IgG4-RKD and may cause acute or chronic renal dysfunction,
      although some glomerular lesions such as membranous nephropathy are sometimes
      evident. Radiologically, several characteristic abnormalities are often
      demonstrated, sometimes mimicking malignancies. IgG4-RKD predominantly affects
      middle-aged to elderly men, and most patients have accompanying IgG4-related
      extrarenal lesions such as sialadenitis, lymphadenopathy, or type 1 autoimmune
      pancreatitis. Serology usually demonstrates high levels of serum total IgG and
      IgG4, and high levels of serum IgE and hypocomplementemia are also frequent
      features. Corticosteroid therapy is usually quite effective, leading to
      amelioration of the renal dysfunction and radiological and serological
      abnormalities. However, as any delay in treatment may result in irreversible
      renal failure, early diagnosis and appropriate therapy are very important.
      Despite these distinctive clinicopathological features of IgG4-RKD, its
      pathogenesis remains poorly understood. Awareness of this condition and
      accumulation of more cases worldwide are necessary. 

PMID- 24107850
TI  - Disaster nephrology: crush injury and beyond.
AB  - Disasters result in a substantial number of renal challenges, either by the
      creation of crush injury in victims trapped in collapsed buildings or by the
      destruction of existing dialysis facilities, leaving chronic dialysis patients
      without access to their dialysis units, medications, or medical care. Over the
      past two decades, lessons have been learned from the response to a number of
      major natural disasters that have impacted significantly on crush-related acute
      kidney injury and chronic dialysis patients. In this paper we review the
      pathophysiology and treatment of the crush syndrome, as summarized in recent
      clinical recommendations for the management of crush syndrome. The importance of
      early fluid resuscitation in preventing acute kidney injury is stressed, logistic
      difficulties in disaster conditions are described, and the need for an
      implementation of a renal disaster relief preparedness program is underlined. The
      role of the Renal Disaster Relief Task Force in providing emergency disaster
      relief and the logistical support required is outlined. In addition, the
      importance of detailed education of chronic dialysis patients and renal unit
      staff in the advance planning for such disasters and the impact of displacement
      by disasters of chronic dialysis patients are discussed. 

PMID- 24107852
TI  - Bicarbonate therapy for prevention of chronic kidney disease progression.
AB  - Kidney injury in chronic kidney disease (CKD) is likely multifactorial, but
      recent data support that a component is mediated by mechanisms used by the kidney
      to increase acidification in response to an acid challenge to systemic acid-base
      status. If so, systemic alkalization might attenuate this acid-induced component
      of kidney injury. An acid challenge to systemic acid-base status increases
      nephron acidification through increased production of endothelin, aldosterone,
      and angiotensin II, each of which can contribute to kidney inflammation and
      fibrosis that characterizes CKD. Systemic alkalization that ameliorates an acid
      challenge might attenuate the contributions of angiotensin II, endothelin, and
      aldosterone to kidney injury. Some small clinical studies support the efficacy of
      alkalization in attenuating kidney injury and slowing glomerular filtration rate
      decline in CKD. This review focuses on the potential that orally administered
      NaHCO3 prevents CKD progression and additionally addresses its mechanism of
      action, side effects, possible complications, dosage, interaction, galenic form
      description, and contraindications. Current National Kidney Foundation guidelines
      recommend oral alkali, including NaHCO3(-), in CKD patients with serum HCO3(-)
      <22 mmol/l. Although oral alkali can be provided by other medications and by base
      inducing dietary constituents, oral NaHCO3 will be the focus of this review
      because of its relative safety and apparent efficacy, and its comparatively low
      cost.

PMID- 24107851
TI  - Potential use of biomarkers in acute kidney injury: report and summary of
      recommendations from the 10th Acute Dialysis Quality Initiative consensus
      conference.
AB  - Over the last decade there has been considerable progress in the discovery and
      development of biomarkers of kidney disease, and several have now been evaluated
      in different clinical settings. Although there is a growing literature on the
      performance of various biomarkers in clinical studies, there is limited
      information on how these biomarkers would be utilized by clinicians to manage
      patients with acute kidney injury (AKI). Recognizing this gap in knowledge, we
      convened the 10th Acute Dialysis Quality Initiative meeting to review the
      literature on biomarkers in AKI and their application in clinical practice. We
      asked an international group of experts to assess four broad areas for biomarker
      utilization for AKI: risk assessment, diagnosis, and staging; differential
      diagnosis; prognosis and management; and novel physiological techniques including
      imaging. This article provides a summary of the key findings and recommendations
      of the group, to equip clinicians to effectively use biomarkers in AKI. 

PMID- 24107854
TI  - Spooky sodium balance.
AB  - Current teaching states that when sodium intake is increased from low to high
      levels, total-body sodium (TBNa) and water increase until daily sodium excretion
      again equals intake. When sodium intake is reduced, sodium excretion briefly
      exceeds intake until the excess TBNa and water are eliminated, at which point
      sodium excretion again equals intake. However, careful balance studies oftentimes
      conflict with this view and long-term studies suggest that TBNa fluctuates
      independent of intake or body weight. We recently performed the opposite
      experiment in that we fixed sodium intake for several weeks at three levels of
      sodium intake and collected all urine made. We found weekly (circaseptan)
      patterns in sodium excretion that were inversely related to aldosterone and
      directly to cortisol. TBNa was not dependent on sodium intake but instead
      exhibited far longer (>= monthly) infradian rhythms independent of extracellular
      water, body weight, or blood pressure. The findings are consistent with our ideas
      on tissue sodium storage and its regulation that we developed on the basis of
      animal research. We are implementing (23)Na-magnetic resonance imaging (MRI) to
      pursue open questions on sodium balance in patients. Our findings could be
      relevant to therapeutic strategies for hypertension and target-organ damage.

PMID- 24107853
TI  - Asymmetric dimethylarginine accumulates in the kidney during ischemia/reperfusion
      injury.
AB  - Ischemia/reperfusion injury is the leading cause of acute tubular necrosis.
      Nitric oxide has a protective role against ischemia/reperfusion injury; however,
      the role of asymmetric dimethylarginine (ADMA), an endogenous inhibitor of nitric
      oxide synthase, in ischemia/reperfusion injury remains unclear. ADMA is produced
      by protein arginine methyltransferase (PRMT) and is mainly degraded by
      dimethylarginine dimethylaminohydrolase (DDAH). Here we examined the kinetics of
      ADMA and PRMT and DDAH expression in the kidneys of ischemia/reperfusion-injured
      mice. After the injury, DDAH-1 levels were decreased and renal and plasma ADMA
      values were increased in association with renal dysfunction. Renal ADMA was
      correlated with 8-hydroxy-2'-deoxyguanosine, a marker of oxidative stress. An
      antioxidant, N-acetylcysteine, or a proteasomal inhibitor, MG-132, restored these
      alterations. Infusion of subpressor dose of ADMA exacerbated renal dysfunction,
      capillary loss, and tubular necrosis in the kidneys of ischemia/reperfusion
      injured wild mice, while damage was attenuated in DDAH transgenic mice. Thus,
      ischemia/reperfusion injury-induced oxidative stress may reduce DDAH expression
      and cause ADMA accumulation, which may contribute to capillary loss and tubular
      necrosis in the kidney. 

PMID- 24107855
TI  - Expanding dynamic kinetic protocols: transaminase-catalyzed synthesis of alpha
      substituted beta-amino ester derivatives.
AB  - Several alpha-alkylated beta-amino esters have been obtained via DKR processes
      employing a kit of transaminases and isopropylamine as an amino donor in aqueous
      medium under mild conditions. Thus, while acyclic alpha-alkyl-beta-keto esters
      afforded excellent conversions and enantioselectivities, although usually low
      diastereoselectivities, using more constrained cyclic beta-keto esters high to
      excellent inductions were obtained. 

PMID- 24107857
TI  - Effect of a school-based active play intervention on sedentary time and physical
      activity in preschool children.
AB  - Early childhood is a critical time for promoting physical activity. Few studies
      have investigated the effect of interventions in this population. The aim of this
      study was to investigate the effect of a school-based active play intervention on
      preschool children's sedentary time and physical activity. Preschool children
      were recruited from randomly selected preschools. Schools were randomly assigned
      to an intervention or comparison group. One teacher per intervention school
      received training from active play professionals in the delivery of a 6-week
      active play programme. Comparison schools continued their usual practice.
      Children wore a uni-axial accelerometer for 7 days at baseline, immediately after
      and at 6-month post-intervention. No significant intervention effects were
      observed for sedentary time or physical activity. However, sex and hours spent at
      school were significant predictors of physical activity. Children who spent fewer
      hours (half-day children) at school were significantly more active than their
      full-day counterparts. Physical activity during the intervention classes was high
      even though neither daily physical activity nor sedentary time changed. Notably
      children who spent more time at preschool were less active suggesting that
      preschool was not as conducive to physical activity engagement as other
      environments. 

PMID- 24107856
TI  - Process evaluation results from the HEALTHY nutrition intervention to modify the
      total school food environment.
AB  - The process evaluation of HEALTHY, a large multi-center trial to decrease type 2
      diabetes mellitus in middle school children, monitored the implementation of the
      intervention to ascertain the extent that components were delivered and received
      as intended. The purpose of this article is to report the process evaluation
      findings concerning the extent to which the HEALTHY nutrition intervention was
      implemented during the HEALTHY trial. Overall, the observed fidelity of
      implementing nutrition strategies improved from baseline to the end of the study.
      By the last semester, all but two nutrition process evaluation goals were met.
      The most challenging goal to implement was serving high fiber foods, including
      grain-based foods and legumes. The easiest goals to implement were lowering the
      fat content of foods offered and offering healthier beverages. The most
      challenging barriers experienced by research dietitians and food service staff
      were costs, availability of foods and student acceptance. Forming strong
      relationships between the research dietitians and food service staff was
      identified as a key strategy to meet HEALTHY nutrition goals. 

PMID- 24107858
TI  - Asthma treatment outcome in adults is associated with rs9910408 in TBX21 gene.
AB  - Inhaled corticosteroids (ICS) are one of the most commonly used asthma therapies
      and have highly variable treatment success. Polymorphisms in TBX21, a gene
      important for the biological action of corticosteroids, could be associated with
      treatment response in asthmatics. We genotyped for rs9910408 in TBX21 in 208
      adult asthmatic patients, treated at least 3 years with ICS. Polymorphism
      rs9910408 was associated with response to ICS treatment. When treatment success
      was assessed by a decrease in bronchial hyperresponsiveness (BHR), the frequency
      of AA genotype was significantly higher in good responders (P = 0.049). This
      genotype related response was even more evident in the subgroups of non-smokers
      (P = 0.008) and in non-atopic patients (P = 0.009). AA genotype was
      overrepresented among good responders according to changes in FEV1 in the
      subgroups of non-smokers (P = 0.013) and in non-atopic patients (P = 0.048). Our
      results showed that treatment response to ICS, assessed as changes in BHR and
      FEV1, is associated with TBX21.

PMID- 24107860
TI  - Sensitivity of MRI of the spine compared with CT myelography in orthostatic
      headache with CSF leak.
AB  - OBJECTIVE: To investigate the sensitivity of MRI of the spine compared with CT
      myelography (CTM) in detecting CSF leaks. METHODS: Between July 1998 and October
      2010, 12 patients with orthostatic headache and a CTM-confirmed spinal CSF leak
      underwent an MRI of the spine with and without contrast. Using CTM as the gold
      standard, we retrospectively investigated the sensitivity of spinal MRI in
      detecting a CSF leak. RESULTS: Eleven of 12 patients with a CSF leak documented
      by CTM also had extradural fluid collections on spinal MRI (sensitivity 91.7%).
      Six patients with extradural fluid collections on spinal MRI also had spinal
      dural enhancement. CONCLUSION: When compared with the gold standard of CTM, MRI
      of the spine appears to be a sensitive and less invasive imaging modality for
      detecting a spinal CSF leak, suggesting that MRI of the spine should be the
      imaging modality of first choice for the detection of spinal CSF leaks.

PMID- 24107861
TI  - MRI and pathology of REM sleep behavior disorder in dementia with Lewy bodies.
AB  - OBJECTIVE: To determine structural MRI and digital microscopic characteristics of
      REM sleep behavior disorder in individuals with low-, intermediate-, and high
      likelihood dementia with Lewy bodies (DLB) at autopsy. METHODS: Patients with
      autopsy-confirmed low-, intermediate-, and high-likelihood DLB, according to the
      probability statement recommended by the third report of the DLB Consortium, and
      antemortem MRI, were identified (n = 75). The clinical history was assessed for
      presence (n = 35) and absence (n = 40) of probable REM sleep behavior disorder
      (pRBD), and patients' antemortem MRIs were compared using voxel-based
      morphometry. Pathologic burdens of phospho-tau, beta-amyloid, and alpha-synuclein
      were measured in regions associated with early neuropathologic involvement, the
      hippocampus and amygdala. RESULTS: pRBD was present in 21 patients (60%) with
      high-likelihood, 12 patients (34%) with intermediate-likelihood, and 2 patients
      (6%) with low-likelihood DLB. Patients with pRBD were younger, more likely to be
      male (p <= 0.001), and had a more frequent neuropathologic diagnosis of diffuse
      (neocortical) Lewy body disease. In the hippocampus and amygdala, phospho-tau and
      beta-amyloid burden were lower in patients with pRBD compared with those without
      pRBD (p < 0.01). alpha-Synuclein burden did not differ in the hippocampus, but
      trended in the amygdala. Patients without pRBD had greater atrophy of
      temporoparietal cortices, hippocampus, and amygdala (p < 0.001) than those with
      pRBD; atrophy of the hippocampus (p = 0.005) and amygdala (p = 0.02) were
      associated with greater phospho-tau burdens in these regions. CONCLUSION:
      Presence of pRBD is associated with a higher likelihood of DLB and less severe
      Alzheimer-related pathology in the medial temporal lobes, whereas absence of pRBD
      is characterized by Alzheimer-like atrophy patterns on MRI and increased phospho
      tau burden.

PMID- 24107863
TI  - Presurgical connectome and postsurgical seizure control in temporal lobe
      epilepsy.
AB  - OBJECTIVES: The objective of this study was to evaluate whether patients with
      surgically refractory medial temporal lobe epilepsy (MTLE) exhibit a distinct
      pattern of structural network organization involving the temporal lobes and
      extratemporal regions. METHODS: We retrospectively studied 18 healthy controls
      and 20 patients with medication refractory unilateral MTLE who underwent anterior
      temporal lobectomy for treatment of seizures. Patients were classified as seizure
      free or not seizure-free at least 1 year after surgery. The presurgical brain
      connectome was calculated through probabilistic connectivity from MRI-diffusion
      tensor imaging from 83 anatomically defined regions of interest encompassing the
      whole brain. The connectivity patterns were analyzed regarding group differences
      in regional connectivity and network graph properties. RESULTS: Compared with
      controls, patients exhibited a decrease in connectivity involving ipsilateral
      thalamocortical regions, with a pathologic increase in ipsilateral medial
      temporal lobe, insular, and frontal connectivity. Among patients, those not
      seizure-free exhibited a higher connectivity between structures in 1) the
      ipsilateral medial and lateral temporal lobe, 2) the ipsilateral medial temporal
      and parietal lobe, and 3) the contralateral temporal pole and parietal lobe.
      Patients not seizure-free also exhibited lower small-worldness in the subnetwork
      within the ipsilateral temporal lobe, with higher subnetwork integration at the
      expense of segregation. CONCLUSIONS: MTLE is associated with network
      rearrangement within, but not restricted to, the temporal lobe ipsilateral to the
      onset of seizures. Networks involving key components of the medial temporal lobe
      and structures traditionally not removed during surgery may be associated with
      seizure control after surgical treatment of MTLE.

PMID- 24107862
TI  - Cortical superficial siderosis and intracerebral hemorrhage risk in cerebral
      amyloid angiopathy.
AB  - OBJECTIVE: To investigate whether cortical superficial siderosis (cSS) on MRI,
      especially if disseminated (involving more than 3 sulci), increases the risk of
      future symptomatic lobar intracerebral hemorrhage (ICH) in cerebral amyloid
      angiopathy (CAA). METHODS: European multicenter cohort study of 118 patients with
      CAA (104 with baseline symptomatic lobar ICH) diagnosed according to the Boston
      criteria. We obtained baseline clinical, MRI, and follow-up data on symptomatic
      lobar ICH. Using Kaplan-Meier and Cox regression analyses, we investigated cSS
      and ICH risk, adjusting for known confounders. RESULTS: During a median follow-up
      time of 24 months (interquartile range 9-44 months), 23 of 118 patients (19.5%,
      95% confidence interval [CI]: 12.8%-27.8%) experienced symptomatic lobar ICH. Any
      cSS and disseminated cSS were predictors of time until first or recurrent ICH
      (log-rank test: p = 0.0045 and p = 0.0009, respectively). ICH risk at 4 years was
      25% (95% CI: 7.6%-28.3%) for patients without siderosis; 28.9% (95% CI: 7.7%
      76.7%) for patients with focal siderosis; and 74% (95% CI: 44.1%-95.7%) for
      patients with disseminated cSS (log-rank test: p = 0.0031). In Cox regression
      models, any cSS and disseminated cSS were both independently associated with
      increased lobar ICH risk, after adjusting for >= 2 microbleeds and age (hazard
      ratio: 2.53; 95% CI: 1.05-6.15; p = 0.040 and hazard ratio: 3.16; 95% CI: 1.35
      7.43; p = 0.008, respectively). These results remained consistent in sensitivity
      analyses including only patients with symptomatic lobar ICH at baseline.
      CONCLUSIONS: Our findings indicate that cSS, particularly if disseminated, is
      associated with an increased risk of symptomatic lobar ICH in CAA. cSS may help
      stratify future bleeding risk in CAA, with implications for prognosis and
      treatment.

PMID- 24107864
TI  - C9ORF72 transcription in a frontotemporal dementia case with two expanded
      alleles.
AB  - Discovery of intronic hexanucleotide repeat expansions of the C9ORF72 gene in a
      significant proportion of patients with amyotrophic lateral sclerosis (ALS) and
      frontotemporal dementia (FTD)(1,2) was an important step for research into these
      disorders. The C9ORF72 genetic variant is more common than other described
      mutations and, unlike patients with mutations in SOD1, C9ORF72-ALS clinically and
      pathologically resembles the more numerous sporadic form.(3) However, progress
      has been limited by lack of understanding of the function of the C9ORF72 locus in
      health and disease. It is unknown whether the expansion causes disease by a gain
      of toxicity, or whether it disrupts expression of the wild-type protein encoded
      by the C9ORF72 gene, or some combination of both mechanisms.(1,2,4.) 

PMID- 24107865
TI  - Quality of life after TIA and stroke: ten-year results of the Oxford Vascular
      Study.
AB  - OBJECTIVE: To evaluate the 5-year impact of stroke and TIA on utility and quality
      adjusted survival. METHODS: TIA and stroke patients from a UK population-based
      study (Oxford Vascular Study) were recruited from 2002 to 2007, and followed up
      until 2012. Quality of life was assessed over 5 years using the EQ-5D (EuroQol-5
      Dimensions), with responses converted into utilities ranging from -0.59 (worse
      than death) to 1 (perfect health), using UK population valuations. Utilities for
      stroke and TIA patients were compared with those in matched controls obtained
      from the 2006 Health Survey for England. Five-year quality-adjusted life years
      were estimated by combining utility and survival information. RESULTS: Four
      hundred forty TIA and 748 stroke patients were ascertained and included. Utility
      remained constant at approximately 0.78 over the 5 years after TIA. Utility
      improved from 0.64 one month after stroke to 0.70 at 6 months (p = 0.006),
      remaining at approximately 0.70 thereafter. Matched controls had considerably
      higher utility levels than stroke/TIA patients (0.85, p < 0.001). Event severity
      and recurrent stroke were significant predictors of decreased long-term utility.
      Five-year quality-adjusted life expectancy was 3.32 (95% confidence interval:
      3.22-3.48) quality-adjusted life years after TIA and 2.21 (2.15-2.37) after
      stroke, varying considerably by severity (minor: 2.94; moderate: 1.65; and
      severe: 0.70). CONCLUSION: Quality-adjusted survival is low over the 5 years
      after stroke and TIA, with severity and recurrent stroke being major predictors.
      There remains considerable scope for improvements in acute treatment and
      secondary prevention to improve the quality of life after TIA and stroke.

PMID- 24107867
TI  - Hemosiderin deposition in the brain as footprint of high-altitude cerebral edema.
AB  - OBJECTIVE: Based on recent findings of microhemorrhages (MHs) in the corpus
      callosum (CC) in 3 individuals after nonfatal high-altitude cerebral edema
      (HACE), we hypothesized that hemosiderin depositions in the brain after high
      altitude exposure are specific for HACE and remain detectable over many years.
      METHODS: This was a cross-sectional study involving 37 mountaineers in 4 groups:
      10 had experienced HACE, 8 high-altitude pulmonary edema, 11 severe acute
      mountain sickness, and 8 had climbed to altitudes >=6,962 m without developing
      any high-altitude illness. HACE was defined as ataxia necessitating assistance
      with walking and/or decreased consciousness. Within <1 to 38 months after the
      qualifying incident, MRI of the brain was performed using a 3-tesla scanner and
      high-resolution susceptibility-weighted magnetic resonance sequences for
      detection of hemosiderin depositions, which were quantified by a score. RESULTS:
      Unequivocal MHs located in the splenium of the CC were found in 8 subjects and
      questionable MHs were found in 2 subjects 1 to 35 months after HACE. They were
      located outside the CC in 5 more severe cases. MHs remained unchanged in those
      reexamined after 12 to 50 months. A few unequivocal MHs in the splenium of the CC
      were found in one subject after severe acute mountain sickness, while one subject
      with high-altitude pulmonary edema and 2 of the extreme altitude climbers had
      questionable lesions. In all other subjects, MHs were unequivocally absent.
      CONCLUSIONS: MHs detectable by susceptibility-weighted MRI predominantly in the
      splenium of the CC are long-lasting footprints of HACE.

PMID- 24107866
TI  - Primary leptomeningeal lymphoma: International Primary CNS Lymphoma Collaborative
      Group report.
AB  - OBJECTIVE: To evaluate clinical presentation, optimal diagnostic evaluation and
      treatment, and outcome in primary leptomeningeal lymphoma, a rare form of primary
      CNS lymphoma without parenchymal or systemic involvement. METHODS: The
      International Primary CNS Lymphoma Collaborative Group, a multidisciplinary group
      of physicians with a particular interest in primary CNS lymphoma, retrospectively
      identified cases of lymphoma isolated to the leptomeninges as diagnosed by CSF
      cytology, flow cytometry, or biopsy, without systemic or parenchymal brain/spinal
      cord lymphoma or immunodeficiency. RESULTS: Forty-eight patients were identified,
      with median age at diagnosis of 51 years and median Eastern Cooperative Oncology
      Group performance status of 2. Presenting symptoms were multifocal in 68%.
      Leptomeningeal enhancement was seen in 74% and CSF profile was abnormal in all
      cases. CSF cytology detected malignant lymphocytes in 67%. Flow cytometry
      identified monoclonal population in 80%, as did receptor gene rearrangement
      studies in 71%. Sixty-two percent had B-cell lymphoma, 19% T-cell, and 19%
      unclassified. Treatment varied and included fractionated radiotherapy (36%),
      systemic chemotherapy (78%), and intra-CSF chemotherapy (66%), with 66% receiving
      >= 2 modalities. Seventy-one percent had a favorable clinical response;
      ultimately, 44% received salvage treatment. Median overall survival was 24
      months, with 11 patients still alive at 50 months follow-up. CONCLUSION: Primary
      leptomeningeal lymphoma is a rare form of primary CNS lymphoma. Patients usually
      present with multifocal symptoms, with evidence of leptomeningeal enhancement and
      diagnostic CSF analysis. Although treatment is highly variable, patients have a
      better prognosis than previously reported and a subset may be cured.

PMID- 24107868
TI  - Extending the KCNQ2 encephalopathy spectrum: clinical and neuroimaging findings
      in 17 patients.
AB  - OBJECTIVES: To determine the frequency of KCNQ2 mutations in patients with
      neonatal epileptic encephalopathy (NEE), and to expand the phenotypic spectrum of
      KCNQ2 epileptic encephalopathy. METHODS: Eighty-four patients with unexplained
      NEE were screened for KCNQ2 mutations using classic Sanger sequencing. Clinical
      data of 6 additional patients with KCNQ2 mutations detected by gene panel were
      collected. Detailed phenotyping was performed with particular attention to
      seizure frequency, cognitive outcome, and video-EEG. RESULTS: In the cohort, we
      identified 9 different heterozygous de novo KCNQ2 missense mutations in 11 of 84
      patients (13%). Two of 6 missense mutations detected by gene panel were recurrent
      and present in patients of the cohort. Seizures at onset typically consisted of
      tonic posturing often associated with focal clonic jerking, and were accompanied
      by apnea with desaturation. One patient diagnosed by gene panel had seizure onset
      at the age of 5 months. Based on seizure frequency at onset and cognitive
      outcome, we delineated 3 clinical subgroups, expanding the spectrum of KCNQ2
      encephalopathy to patients with moderate intellectual disability and/or
      infrequent seizures at onset. Recurrent mutations lead to relatively homogenous
      phenotypes. One patient responded favorably to retigabine; 5 patients had a good
      response to carbamazepine. In 6 patients, seizures with bradycardia were
      recorded. One patient died of probable sudden unexpected death in epilepsy.
      CONCLUSION: KCNQ2 mutations cause approximately 13% of unexplained NEE. Patients
      present with a wide spectrum of severity and, although rare, infantile epilepsy
      onset is possible.

PMID- 24107869
TI  - Poor reward sensitivity and apathy after stroke: implication of basal ganglia.
AB  - OBJECTIVE: To examine the relationship between reward sensitivity and self
      reported apathy in stroke patients and to investigate the neuroanatomical
      correlates of both reward sensitivity and apathy. METHODS: In this prospective
      study, 55 chronic stroke patients were administered a questionnaire to assess
      apathy and a laboratory task to examine reward sensitivity by measuring
      motivationally driven behavior ("reinforcement-related speeding"). Fifteen
      participants without brain damage served as controls for the laboratory task.
      Negative mood, working memory, and global cognitive functioning were also
      measured to determine whether reward insensitivity and apathy were secondary to
      cognitive impairments or negative mood. Voxel-based lesion-symptom mapping was
      used to explore the neuroanatomical substrates of reward sensitivity and apathy.
      RESULTS: Participants showed reinforcement-related speeding in the highly
      reinforced condition of the laboratory task. However, this effect was significant
      for the controls only. For patients, poorer reward sensitivity was associated
      with greater self-reported apathy (p < 0.05) beyond negative mood and after
      lesion size was controlled for. Neither apathy nor reward sensitivity was related
      to working memory or global cognitive functioning. Voxel-based lesion-symptom
      mapping showed that damage to the ventral putamen and globus pallidus, dorsal
      thalamus, and left insula and prefrontal cortex was associated with poorer reward
      sensitivity. The putamen and thalamus were also involved in self-reported apathy.
      CONCLUSIONS: Poor reward sensitivity in stroke patients with damage to the
      ventral basal ganglia, dorsal thalamus, insula, or prefrontal cortex constitutes
      a core feature of apathy. These results provide valuable insight into the neural
      mechanisms and brain substrate underlying apathy.

PMID- 24107870
TI  - Spinal uptake mimicking metastasis in SPECT/CT bone scan in a patient with
      superior vena cava obstruction.
AB  - A 46-year-old female patient with a mediastinal neuroendocrine carcinoma
      complicated by superior vena cava syndrome was referred for a bone metastatic
      workup. Bone scan with SPECT/CT showed several vertebral fixations without
      alterations on the unenhanced CT, but a CT scan with injection of contrast media
      showed vertebral densities matched to the lesions described on the SPECT/CT. This
      pattern confirmed presence of collateral paths through vertebral veins due to
      superior vena cava syndrome. Lack of metastases was confirmed by MRI. 

PMID- 24107871
TI  - Intense iodine activity caused by mosquito bite.
AB  - A 12-year-old girl with a history of papillary thyroid cancer underwent
      radioiodine remnant ablation using (131)I. Posttherapy whole-body (131)I
      scintigraphy revealed not only the known activity in the neck but also increased
      activity in the superficial posterior right upper thigh. On further clinical
      evaluation, the patient was found to have a mosquito bite with surrounding
      hyperemia at the site of the abnormal activity.

PMID- 24107872
TI  - Unusual cationic rhodathiaboranes: synthesis and characterization of [8,8,8
      (H)(PR3)2-9-(Py)-nido-8,7-RhSB9H10]+ and [1,3-MU-(H)-1,1-(PR3)2-3-(Py)-isonido
      1,2-RhSB9H8]+.
AB  - The treatment of the hydridorhodathiaboranes, [8,8,8-(H)(PR3)2-9-(Py)-nido-8,7
      RhSB9H9], where PR3 = PPh3 (2), PMePh2 (3), PPh3 and PMe2Ph (4), or PMe3 and PPh3
      (5), and [8,8,8-(H)(PMePh2)2-9-(PMePh2)-nido-8,7-RhSB9H9] (6), with TfOH affords
      [8,8,8-(H)(PR3)2-9-(Py)-nido-8,7-RhSB9H10](+) cations, where PR3 = PPh3 (12),
      PMePh2 (13), PPh3 and PMe2Ph (14), or PMe3 and PPh3 (15), and [8,8,8-(H)(PMePh2)2
      9-(PMePh2)-nido-8,7-RhSB9H10](+) (16). Compounds 13 and 14 lose H2 to give [1,3
      MU-(H)-1,1-(PR3)2-3-(Py)-isonido-1,2-RhSB9H8](+), where PR3 = PMe2Ph (18), PPh3
      and PMe2Ph (21), or PMePh2 (22). Similarly, the 11-vertex rhodathiaboranes, [1,1
      (PR3)2-3-(Py)-1,2-RhSB9H8], where PR3 = PPh3 (7), PMe2Ph (8), PMe3 (9), or PPh3
      and PMe3 (10), react with TfOH to give the corresponding cations, [1,3-MU-(H)-1,1
      (PR3)2-3-(Py)-isonido-1,2-RhSB9H8](+), where PR3 = PPh3 (17), PMe2Ph (18), PMe3
      (19), or PPh3 and PMe3 (20). Four conformers of 20 are studied by X-ray
      diffraction methods and DFT-calculations, identifying packing motifs that
      stabilize different metal-thiaborane linkages, and energy variations that are
      involved in these conformational changes. It is demonstrated that the proton
      induces nonrigidity on these clusters as well as an enhancement of their Lewis
      acidity.

PMID- 24107873
TI  - [Mental health in the Russian Federation in 1992-2010].
AB  - At the population level, the quantitative assessment of the impact of social
      economic and medical-demographic factors on the dynamics of main mental health
      indicators (prevalence, incidence, level of suicide, disability) in the
      population of the Russian Federation in 1992-2010 years is presented. Regression
      models relating the key indicators of mental health with the health-demographic
      and social-economic factors have been developed. The interpretation of the
      dynamics of mental health in Russia according to the social changes and living
      conditions in the country during 1992-2010 years is suggested. Models have good
      predictive performance, which allows their use as a tool for real-time monitoring
      and planning of health and social services. 

PMID- 24107874
TI  - [Clinical typology of organic psychosis in children and adolescents].
AB  - Observation of a group of children and adolescents, aged 8-17 years, with organic
      psychosis are reviewed. Four main variants, including organic schizoid psychoses;
      organic affective psychoses; periodic organic psychoses and organic hallucinosis,
      are described. 

PMID- 24107875
TI  - [Piascledin in the treatment of chronic dorsalgia].
AB  - Piascledine is a plant drug which positively influences the metabolism of
      cartilage and bone tissues. The authors studied the therapeutic effect of the
      drug in outpatients with chronic nonspecific dorsalgia. Piascledine was
      administered in dose 300 mg daily during two months. In the first month, it was
      used in the combination with artrosilene (320 mg daily). A comparison group
      included patients receiving monotherapy with NSAIDs (artrosilene). The study
      confirmed the high analgesic efficacy of piascledine in the treatment of patients
      with chronic nonspecific dorsalgia with controlled using of NSAIDs. The positive
      effect of piascledine was demonstrated after one month of treatment. The authors
      suggest that further clinical trials and placebo-control studies are needed to
      confirm these results. 

PMID- 24107876
TI  - [The experience treatment of adjunctive lacosamide for patients with drug
      resistance partial epilepsy].
AB  - The aim of the study was to evaluate the efficacy and safety of lacosamide (100
      400 mg per day) as adjunctive treatment to other antiepileptic drugs (AED) in
      patients with uncontrolled partial epilepsy. A retrospective evaluation of
      efficacy and safety of lacosamide was made in 56 patients, aged 17-58 years, with
      focal seizures with- or without secondary localization during 6 months.
      Lacosamide was used with other AED (carbamazepine, oxcarbazepine, lamotrigine,
      valproates, levetiracetam, topiramate); in 73,2% patients it was administered
      with two additional AED. In 69,6% patients, the dose of lacosamide was 300 mg per
      day. The complete cessation of seizures was achieved in 8 (14,3%) patients, 18
      (32,1%) patients had 50-75% reduction in seizures, 17 (30,4%) had 50% reduction.
      There were no changes in 3 (23,2) patients. Dose-dependent adverse effects were
      diplopia, vertigo, sleepiness, skin allergic reactions. No side-effects were
      caused by drug intolerance. Lacosamide is believed to open new possibilities in
      treatment of epilepsy. 

PMID- 24107877
TI  - [Possibilities of pharmacological modulation of brain glutamatergic system in the
      treatment of vascular cognitive impairment].
AB  - An aim of the study was to investigate the efficacy and safety of noojerone
      (memantine) in patients with cognitive impairment comorbid to brain ischemia,
      stages II-III. The main group (30 patients, aged 64-86 years) was treated with
      noojerone in addition to standard therapy according to dosage scheme during 6
      months. The control group (15 patients, aged 61-78 years) received standard
      therapy only. Patients underwent somatic and neurological examinations, along
      with neuropsychological testing (MMSE, FAB and other tests). The use of noojerone
      in complex treatment decreased cognitive impairment in the main group compared to
      the control one. The most distinct changes were noted on MMSE. Statistically
      significant changes appeared during the 12th week. The maximal effect was
      observed when the drug was applied during 6 months. Noojerone was well-tolerated
      by the patients. 

PMID- 24107878
TI  - [A study of the efficacy and safety of valdoxan in the treatment of a depressive
      episode].
AB  - An open non-randomized controlled prospective study was conducted to investigate
      the efficacy and safety of valdoxan in the treatment of depression as monotherapy
      and in the combination with other drugs. Based on the clinical and psychometric
      measures, author confirmed the high efficacy of valdoxan. The drug can be
      combined with other antidepressants, no adverse effects are observed in these
      cases. Positive changes in sleep patterns during the treatment with valdoxan were
      found. The high tolerability and minimal risk of serious adverse effects were
      observed. Preliminary data revealed that the age of the patient and scores on
      some HAMD items were predictors of treatment efficacy. The authors developed a
      computer program for express-assessment of probability of remission and response
      to treatment. 

PMID- 24107879
TI  - [Psychoautonomic disorders in patients with hypertension, stage I and
      possibilities of their treatment].
AB  - The article is devoted to the study of psychoautonomic features of patients with
      essential hypertension stage 1. The authors present the results of the clinical
      and psychological examinations of 62 patients with this pathology. These results
      show an increase in the levels of state and trait anxiety, which confirms the
      leading role of the psycho-emotional sphere in the formation of hypertensive
      reactions. This study evaluated the efficacy of the drug adaptol usage during 8
      weeks in daily dose 1500 mg divided into three parts in the treatment of this
      group of patients. The results clearly demonstrate the positive effect of adaptol
      on psychoautonomic adaptation of patients with essential hypertension stage 1. 

PMID- 24107880
TI  - [Management of cognitive impairment in children and adolescents with cerebral
      palsy treated with pantocalcin].
AB  - A randomized study on the efficacy and safety of the hopantenic acid preparation
      (pantocalcin) and its effect on cognitive functions in children with cerebral
      palsy (CCP) has been carried out. The positive effect of pantocalcin on the
      visual memory and attention concentration, activity and fatigability has been
      shown. At the same time, there was a decrease of anxiety in children and
      adolescents with CCP. No evidence for the effect of the drug on visual-motor
      skills has been found. The results of the study have demonstrated the high safety
      profile of pantocalcin when used in pediatric practice. 

PMID- 24107881
TI  - [Influence of psychosocial therapy on funcioning of adolescents with
      schizophrenia spectrum disorders (a pilot study)].
AB  - Authors studied the influence of psychosocial group therapy (PST) in adolescents
      with schizophrenia spectrum disorders on the dynamics of their social functioning
      based on the PedsQL questionnaire and the CGAS children general functioning
      assessment scale. There was a statistically significant improvement of basic
      indicators of adolescent social functioning in the main group after the PST cycle
      (3 months), while no proven between main and comparison groups difference was
      detected in the therapeutic dynamics, according to the PANSS scale, that
      confirmed the effectiveness of PST inclusion into psychosocial therapy and
      rehabilitation of adolescents with schizophrenia spectrum disorders. Three groups
      of adolescents were defined within the main group; trends towards changes in
      social functioning, depending on the type of disease course, were noted. 

PMID- 24107882
TI  - [Primary and secondary resistance to nicotine replacement therapy in tobacco
      dependent patients].
AB  - The terms of primary and secondary resistance to nicotine replacement therapy in
      tobacco dependent patients are defined. It is shown that treatment resistance is
      a result of a constellation of special clinical features of tobacco dependence,
      tolerance to nicotine, personality traits of the patients, family history of
      smoking, comorbid affective disorders and somatic diseases. 

PMID- 24107883
TI  - [Ultrastructural pathology of myelinated fibers in schizophrenia].
AB  - An electron microscopic morphometric study of myelinated fibers and proportions
      of pathological myelinated fibers in postmortem prefrontal cortex, caudate
      nucleus and hippocampus was performed in 25 cases with schizophrenia and 25
      normal controls. Pathology of myelinated fibers was similar in all brain
      structures in schizophrenia and included focal destruction of myelin sheaths and
      atrophy of axons. These changes were not correlated with age, postmortem delay or
      neuroleptic exposure but they were significantly positively correlated with the
      age at onset of disease. The proportion of myelinated fibers with axonal atrophy
      was the most prominent in the prefrontal cortex and significantly positively
      correlated with the proportion of these fibers in the caudate nucleus and
      hippocampus. The authors suggest that ultrastructural abnormalities of myelinated
      fibers in schizophrenia might contribute to functional disconnections of the
      prefrontal cortex with other brain structures. 

PMID- 24107885
TI  - [The influence of mental disease on the family environment of the patient:
      results of the sociological questioning].

PMID- 24107884
TI  - [Clinical and genetic analysis of idiopathic intellectual disability based on
      array comparative genomic hybridization].
AB  - In this study authors searched for chromosomal aberrations in 71 children with
      developmental delay or idiopathic mental retardation using Human Genome CGH
      Microarray Kits 4*44K and 8*60K (Agilent Technologies, USA). Microdeletions and
      microduplications, as well as CNV, which may be related to intellectual
      disability and associated with regions of known hereditary diseases or
      chromosomal syndromes were identified in 14 (20%) children (these patients are
      described in this article). During the analysis, candidate genes localized within
      the regions of aberrations and associated with development and functioning of
      nervous system were denoted. 

PMID- 24107886
TI  - [Hemorrhagic syndrome after the treatment with peroral anticoagulants -
      antagonists of vitamin K].

PMID- 24107887
TI  - [The use of mexidol in acute period of ischemic stroke].

PMID- 24107888
TI  - [Monitoring of intracranial pressure and cerebral compliance in patients with
      hemispheric non-traumatic hemorrhages].
AB  - Indicators of intracranial pressure (ICP) and cerebral compliance in 48 patients
      with primary non-traumatic intracerebral hemorrhages who underwent surgery using
      precise aspiration and local fibrinolysis were studied. Based on clinical and
      neuroimaging data, ICP indicators and cerebral compliance, we can evaluate the
      compressive influence of the cerebral hematoma, perform the dynamic control of
      fibrinolysis efficacy and intracerebral hematoma aspiration as well as of
      dislocation syndrome's regress and predict outcomes of disease. The restoration
      of ICP indicators, cerebral compliance and elimination of middle structure
      dislocation can be used as criteria of surgery effectiveness. At the same time,
      the residual volume of the hemorrhage (within 20 ml) during the elimination of
      compression does not exert any significant effect on the course and outcome. 

PMID- 24107889
TI  - [Hyperdensivity of the trunk of the middle cerebral artery on the CT scanning in
      the acute stage of ischemic stroke].
AB  - Twenty-nine patients with massive ischemic stroke (MIS) admitted to the hospital
      in the first 12h after stroke were examined. On the primary CT scan, there were
      no zones with decreased density of brain matter. A subsequent CT was performed on
      the next day to visualize stroke lesions. Correlations between the density of the
      trunk of the middle cerebral artery (MCA) on the primary CT, the volume of the
      lesion on the subsequent CT and the character of disease course were analyzed. It
      was shown that the CT-sign of MCA trunk thrombosis in the acute stage of MIS is a
      highly-specific predictor of MIS but a less effective predictor of an unfavorable
      benign disease course. 

PMID- 24107890
TI  - [The inherited procoagulant and prothrombotic condition as the main etiological
      factor for ischemic stroke in infants].
AB  - The data on the risk factors and etiology of ischemic stroke in 31 infants, aged
      under 3 years, are summarized. The results of genotyping of blood coagulation and
      folic acid gene polymorphisms in patients and 83 healthy people are presented.
      Significant differences were found for -455 G>A FGB (r=0.03) and 807 C>T ITGA2
      (r=0,005) polymorphisms. Different gene-gene combinations that can cause
      hypercoagulation and arterial thrombosis in this age were identified. The most
      frequent combinations include polymorphisms of genes for FGB, fibrinolysis system
      and folate cycle enzymes (OR=3,79 and more, p<0.05). A clinical case of ischemic
      stroke in a girl, aged 10 months, after operated congenital heart malformation is
      presented. 

PMID- 24107891
TI  - [The association between oxidative stress markers and clinical course of chronic
      cerebral ischemia].
AB  - Authors studied 360 patients with different stages of chronic cerebral ischemia
      (CBI), including 180 patients followed-up for 12 months after the first
      examination, who were stratified into two groups with regard to disease course -
      favorable (stable) and unfavorable (progressive or with acute episodes of
      cerebral blood circulation disturbance). Oxidative stress markers were evaluated
      by the level of lipid- (malonic dialdehyde) and protein - (carbon products of
      protein oxidation, the level of plasma SH-groups, the accumulation of the
      products of deep oxidation of proteins) oxidation. Along with indicators of
      oxidative stress, we evaluated the binding capacity of albumin using fluorescent
      probe K-35. Initial level of these markers and their concentrations after the
      copper ion induced oxidation of the plasma were determined. The highest increase
      in oxidative stress indicators was seen in patients with acute episodes. Authors
      identified significant differences in these indicators in the groups of patients
      with different clinical variants of CBI course as well as qualitative and
      quantitative diagnostic criteria of unfavorable course and risk of stroke. Our
      findings suggest that the imbalance of oxidative-antioxidative system contributes
      to the course of CBI. Prediction of unfavorable course of CBI determines the
      timeliness of adequate treatment. 

PMID- 24107892
TI  - [Meteorological risk factors of stroke].
AB  - Based on correlation analysis of stroke, recorded in Khanty-Mansiysk during 5
      years, and standard meteorological factors, we found the significant relationship
      between the frequency of stroke and daily temperature amplitude. The positive
      correlation between the frequency of stroke and between-day changes in air
      temperature in the combination with changes in atmospheric pressure during 3 h
      was identified. A maximal number of strokes was recorded in December, April, May
      and July and a minimal number was in January, June, August and September. The
      frequency of stroke and fatal outcomes did not depend on the season. 

PMID- 24107893
TI  - [Efficacy and safety of mildronate in emergency medical care].
AB  - Detailed clinical data about patients who used emergency services during 2011 are
      presented. The main attention is focused on the state of patients with acute and
      chronic brain ischemia before and after treatment with mildronate. Mean age of
      patients with ischemic stroke and chronic brain ischemia was 63.4 and 57.7 years,
      respectively. Mildronate was injected slowly intravenously in one dose 1000 mg
      (10 ml of 10% solution). The results obtained in the study allow to recommend
      mildronate for such patients and provide the useful information to physicians and
      medical attendants about current methods of diagnosis and treatment of patients
      with acute and chronic brain ischemia in out- and inpatient health services. 

PMID- 24107894
TI  - [Medical and organizational issues of pre- and post-stroke disablement].
AB  - Authors examined 400 patients in the acute stage of ischemic and hemorrhagic
      stroke, including 140 patients who were followed-up for 6 months after the
      discharge. The dynamics of neurological and functional status, degree of
      disability and 6 month mortality were evaluated. It was shown that before
      hospitalization, 45.3% patients had disability pensions group I (14 or 7.7%),
      group II (136 or 75.1%) and group III (31 or 17.1%). The proportion of disabled
      people among able-bodied citizens younger than 60 years was 17.5% and it was
      77.4% among those older than 80 years. Disability was caused by the
      cardiovascular pathology (48.1%), previous stroke (30.9%), diabetes mellitus type
      2 and its complications (21%). The group of disability assigned before stroke,
      degree of comorbidity and severity of main disease were positively correlated
      with the severity of patient's condition on admission to and at discharge from
      the hospital. During 6 months after discharge, 15.7% of patients died, the rate
      of mortality was higher by a factor of 1.5 (21.4%) for secondary stroke compared
      to the first one. The rate of disability increased during 6 months. A number of
      people with disability group I increased by 12%, group II - by 20% , group III -
      by 5% and was estimated as 15, 55.7 and 15%, respectively. 

PMID- 24107895
TI  - [Correction of psychoemotional and autonomic dysfunction in patients with
      ischemic stroke].
AB  - Investigation of 106 patients in the early recovery period of ischemic stroke is
      conducted. Autonomic nervous system dysfunction and the psychoemotional
      disturbances are revealed. Efficacy of mexiprim in the correction of the revealed
      psychoautonomic problems in patients with ischemic stroke is shown. 

PMID- 24107896
TI  - [Dynamics of sensorimotor reactions during early rehabilitation for patients
      after stroke].
AB  - Authors studied sensorimotor reactions in 60 patients with stroke in the early
      stage of rehabilitation and in 20 healthy people. The evaluation of sensorimotor
      reactions using the "Sensoneck" system and functional independence with the
      Functional Independence Measure (FIM) scale was performed in the beginning of
      early stage of rehabilitation and at the discharge from the hospital. Most of
      patients became functionally independent though no statistically significant
      correlations between the FIM scores and "Sensoneck" scores were found to the end
      of rehabilitation. During early rehabilitation, the quality of motion performance
      improved slightly, and sensorimotor reactions improved statistically
      significantly (p<0.05). 

PMID- 24107897
TI  - [Rehabilitation of post-stroke patients with movement disorders].

PMID- 24107898
TI  - [Prevention of stroke in patients with atrial fibrillation: a role of modern
      anticoagulants].
AB  - The review addresses the primary and secondary prevention of cardioembolic
      ischemic stroke, in particular, in patients with non-valvular atrial
      fibrillation. Indications and schemes of anticoagulation treatment, advantages in
      stroke prevention and difficulties in using of the common oral anticoagulant
      warfarin are discussed. The authors compare the mechanism of action, efficacy and
      safety of the peroral anticoagulant rivaroxaban with warfarin. Based on the
      results of large meta-analyses, it has been concluded that the efficacy of
      rivaroxaban is rather superior to warfarin, this drug has the same safety profile
      and is more convenient in use. During treatment, no laboratory monitoring of
      hemostasis indicators is needed. This drug can be recommended for prevention of
      cardioembolic stroke in patients with atrial fibrillation. 

PMID- 24107899
TI  - [Medical care to patients with stroke in the frames of the Federal program in the
      Irkutsk oblast].

PMID- 24107900
TI  - [Organization of specialized medical care to patients with stroke in the
      Krasnodar kray].

PMID- 24107901
TI  - [Standardization of medical care in the Russian Federation: legal aspects].

PMID- 24107902
TI  - Deep brain stimulation for psychiatric diseases: a pooled analysis of published
      studies employing disease-specific standardized outcome scales.
AB  - BACKGROUND: Deep brain stimulation (DBS) has emerged in recent years as a novel
      therapy in the treatment of refractory psychiatric disease, including major
      depressive disorder (MDD), obsessive-compulsive disorder (OCD), and Tourette's
      syndrome (TS). Standardized outcome scales were crucial in establishing that DBS
      was an effective therapy for movement disorders. OBJECTIVE: In order to better
      characterize the evidence supporting DBS for various psychiatric diseases, we
      performed a pooled analysis of those studies which incorporated specific
      standardized rating scales. METHODS: A Medline search was conducted to identify
      all studies reporting DBS for MDD, OCD, and TS. The search yielded a total of 49
      articles, of which 24 were included: 4 related to MDD (n = 48), 10 to OCD (n =
      64), and 10 to TS (n = 46). RESULTS: A meta-analysis of DBS for MDD, OCD, and TS
      in studies employing disease-specific standardized outcome scales showed that the
      outcome scales all improved in a statistically significant fashion for these
      psychiatric diseases. Our pooled analysis suggests that DBS for TS has the
      highest efficacy amongst the psychiatric diseases currently being treated with
      DBS, followed by OCD and MDD. CONCLUSION: DBS for psychiatric diseases remains
      investigational; however, even when studies failing to incorporate standardized
      outcome scales are excluded, there is statistically significant evidence that DBS
      can improve symptoms in MDD, OCD, and TS. Standardized disease-specific outcome
      scales facilitate pooled analysis and should be a required metric in future
      studies of DBS for psychiatric disease.

PMID- 24107903
TI  - Blurry topography for precise target-distance computations in the auditory cortex
      of echolocating bats.
AB  - Echolocating bats use the time from biosonar pulse emission to the arrival of
      echo (defined as echo delay) to calculate the space depth of targets. In the
      dorsal auditory cortex of several species, neurons that encode increasing echo
      delays are organized rostrocaudally in a topographic arrangement defined as
      chronotopy. Precise chronotopy could be important for precise target-distance
      computations. Here we show that in the cortex of three echolocating bat species
      (Pteronotus quadridens, Pteronotus parnellii and Carollia perspicillata),
      chronotopy is not precise but blurry. In all three species, neurons throughout
      the chronotopic map are driven by short echo delays that indicate the presence of
      close targets and the robustness of map organization depends on the parameter of
      the receptive field used to characterize neuronal tuning. The timing of cortical
      responses (latency and duration) provides a binding code that could be important
      for assembling acoustic scenes using echo delay information from objects with
      different space depths. 

PMID- 24107904
TI  - A single slice measure of epicardial adipose tissue can serve as an indirect
      measure of total epicardial adipose tissue burden and is associated with
      obstructive coronary artery disease.
AB  - AIMS: To evaluate the practical use of the single slice measurement of epicardial
      adipose tissue (EAT) at the level of the left main coronary artery (EATLM) in
      predicting the presence of obstructive coronary artery disease (CAD). METHODS AND
      RESULTS: Quantification of EATTotal and EATLM was performed on non-contrast CT
      scans of consecutive patients (without history of revascularization, cardiac
      transplantation, device implantation, and congenital heart disease) who underwent
      coronary artery calcium (CAC) scoring and computed tomographic coronary
      angiography (CTA) between May 2011 and July 2011. One hundred and ninety-two
      patients were evaluated, of which 47 had obstructive CAD (>50% stenosis). EATLM
      (3.8 +/- 2.2 cm(3)) and EATTotal (126.2 +/- 56.3 cm(3)) are highly correlated (r
      = 0.89, P < 0.001). Multivariate analysis revealed that both EATLM (OR: 1.204 per
      1 cm(3), 95% CI: 1.028-1.411, P = 0.021) and EATTotal (OR: 1.007 per 10 cm(3),
      95% CI: 1.000-1.013, P = 0.038) are associated with obstructive CAD. However,
      when the CAC score was added to multivariate analysis, both failed to show
      statistical significance. (EATTotal, OR 1.004 per 1 cm(3), 95% CI: 0.996-1.011, P
      = 0.328 and EATLM, OR: 1.136 per 10 cm(3), 95% CI: 0.948-1.362) ROC curve
      analysis revealed that both EATTotal and EATLM are of incremental value in
      detecting CAD, when compared with clinical risk scores (NCEP plus EATTotal plus
      BMI and NCEP plus EATLM plus BMI vs. NCEP alone; AUC 0.7090, P = 0.009 and
      0.7167, P = 0.003 vs. 0.6069, respectively). CONCLUSION: Measuring epicardial
      adipose tissue on a single slice at the level of the left main coronary artery
      may serve as an indirect measure of total epicardial adipose tissue burden. EATLM
      and EATTotal are independently associated with obstructive coronary artery
      disease and are incremental to traditional risk factors for predicting its
      presence.

PMID- 24107905
TI  - Comparison of clinical non-commercial tools for automated quantification of
      myocardial blood flow using oxygen-15-labelled water PET/CT.
AB  - AIMS: Absolute quantification of myocardial blood flow (MBF) with (15)O-water
      cardiac positron emission tomography (PET)/CT has recently demonstrated to hold
      promising diagnostic value for the detection of coronary artery disease (CAD).
      However, methodological differences in utilized analysis software packages (SP)
      could affect generated MBF values, potentially prohibiting widespread clinical
      applicability of obtained normal thresholds. The aim of this study was to compare
      two validated non-commercial SP, Carimas and Cardiac VUer, for the quantification
      of MBF using (15)O-water PET. METHODS AND RESULTS: One hundred patients with
      intermediate likelihood of CAD and scanned in academic centres in Amsterdam (n =
      50) and Turku (n = 50) were included in the study. Patients underwent a (15)O
      water PET/CT scan during rest and vasodilator stress based on clinical
      indications. A single observer, blinded from clinical results and with no prior
      experience in either SP, analysed all patients twice with both SP.
      Reproducibility of each SP was assessed using intraclass correlation coefficients
      (ICC). Intersoftware agreement was assessed using paired t-tests and linear
      regression. ICC was excellent for each SP for both global and regional MBF (ICC
      >0.90). Global MBF was comparable between Carimas and Cardiac VUer during rest
      (1.02 +/- 0.28 vs. 0.99 +/- 0.23 mL min(-1)g(-1), respectively, P = 0.07), and
      slightly higher for Carimas during stress (2.73 +/- 0.82 vs. 2.63 +/- 0.84 mL
      min(-1)g(-1), respectively, P = 0.01). At a regional level, for resting
      conditions small (<10%) but significant discrepancies were noted in each vascular
      territory while for stress MBF, a significant difference was only observed for
      the LAD region. Differences between SP for the LAD territory were abolished after
      exclusion of the distal apical segment, which is susceptible to spillover
      artefacts. An excellent correlation between MBF values was found for global (r =
      0.96) and regional MBF (r > 0.94 for all). CONCLUSION: For global and regional
      MBF, Carimas and Cardiac VUer showed excellent agreement and intra-observer
      reproducibility. These results confirm that, for patients with intermediate
      likelihood of CAD, these validated SP are interchangeable and can be utilized for
      routine clinical practice of (15)O-water cardiac PET.

PMID- 24107906
TI  - Anxiety, posttraumatic stress, and fear of cancer progression in patients with
      melanoma in cancer aftercare.
AB  - Several studies have described mental distress and anxiety in patients with
      melanoma. The findings of these studies varied from patients with a quality of
      life similar to the general population and those with increased mental distress.
      In the present study, we investigated anxiety, posttraumatic stress, and fear of
      cancer progression to gain a detailed picture of the burdens of these patients.
      PATIENTS AND METHODS: 70 patients with malignant melanoma who attended cancer
      aftercare were surveyed using the psychometric instruments Hospital Anxiety and
      Depression Scale (HADS), Posttraumatic Symptom Scale (PTSS-10), and Fear of
      Progression Questionnaire (FoP-Q). The questionnaires were evaluated and an
      analysis of the single items carried out. RESULTS: The scores for the three
      anxiety parameters were low, but 7% of the patients presented an increased HADS
      score, and 17% an increased PTSS-10 value. An analysis of the items showed that
      patients feared physical disabilities more than mental distress or lack of social
      support. CONCLUSION: Most of the patients perceived themselves as stable, and
      relied on the assistance of their families. However, a small group of patients
      suffered from clinically relevant anxiety; these patients should be given the
      support indicated for their specific distress.

PMID- 24107907
TI  - Evaluation of selected speech parameters after prosthesis supply in patients with
      maxillary or mandibular defects.
AB  - BACKGROUND: Ablative surgery of oropharyngeal tumors frequently leads to defects
      in the speech organs, resulting in impairment of speech up to the point of
      unintelligibility. The aim of the present study was the assessment of selected
      parameters of speech with and without resection prostheses. PATIENTS AND METHODS:
      The speech sounds of 22 patients suffering from maxillary and mandibular defects
      were recorded using a digital audio tape (DAT) recorder with and without
      resection prostheses. Evaluation of the resonance and the production of the
      sounds /s/, /sch/, and /ch/ was performed by 2 experienced speech therapists.
      Additionally, the patients completed a non-standardized questionnaire containing
      a linguistic self-assessment. RESULTS: After prosthesis supply, the number of
      patients with rhinophonia aperta decreased from 7 to 2 while the number of
      patients with intelligible speech increased from 2 to 20. Correct production of
      the sounds /s/, /sch/, and /ch/ increased from 2 to 13 patients. A significant
      improvement of the evaluated parameters could be observed only in patients with
      maxillary defects. The linguistic self-assessment showed a higher satisfaction in
      patients with maxillary defects. CONCLUSION: In patients with maxillary defects
      due to ablative tumor surgery, an increase in speech performance and
      intelligibility is possible by supplying resection prostheses.

PMID- 24107908
TI  - Prognostic factors for recurrence-free survival in patients with HER2-positive
      early-stage breast cancer treated with adjuvant trastuzumab.
AB  - BACKGROUND: The objective of this study was to identify prognostic factors
      affecting the recurrence-free survival (RFS) in patients who received a 52-week
      trastuzumab therapy for HER2-positive early stage breast cancer (EBC). PATIENTS
      AND METHODS: The medical records of all patients with EBC from 10 centers were
      analyzed. Pathologic and clinical tumor characteristics were evaluated in 424
      female patients who received 52 weeks of adjuvant trastuzumab for HER2-positive
      EBC. Survival was estimated using the Kaplan-Meier method. Univariate analyses of
      RFS were performed with the log-rank test. Independent prognostic and predictive
      factors affecting RFS were assessed by Cox regression analysis. RESULTS: Median
      follow-up time was 33.1 months (range 9.2-75.9 months). 3-year RFS and overall
      survival were 87 and 97%, respectively. In multivariate analysis, patients aged
      70 years or over (p = 0.017, relative risk (RR) 2.7, 95% confidence interval (CI)
      1.19-6.13), patients with > 9 positive lymph nodes (p = 0.001, RR 2.52, 95% CI
      1.42-4.46), and those with progesterone receptor-negative tumors (p = 0.006, RR
      2.33, 95% CI 1.27-4.27) had worse RFS. CONCLUSION: In spite of a 52-week adjuvant
      trastuzumab treatment, classic poor prognostic factors for invasive EBC remained
      as such in patients with HER2-positive EBC.

PMID- 24107909
TI  - Meta-analysis of the association between a polymorphism in microRNA-196a2 and
      susceptibility to colorectal cancer.
AB  - BACKGROUND/AIMS: To accurately evaluate the impact of the C/T polymorphism in
      microRNA (miRNA)-196a2 on the colorectal cancer (CRC) risk, by meta-analysis.
      METHODS: An electronic search for articles was conducted in PubMed, EMBASE, ISI
      Web of Science, and the Cochrane Library. The pooled odds ratio (OR) and its 95%
      confidence interval (CI) were used to assess the association through meta
      analysis. RESULTS: 5 studies were used for analysis. The results showed a
      significant association between the miRNA-196a2 C/T polymorphism and CRC risk in
      the genetic models (C vs. T: OR = 1.168, 95% CI = 1.106-1.282, p = 0.001; CC vs.
      TT: OR = 1.368, 95% CI = 1.132-1.654, p = 0.001; TC/CC vs. TT: OR = 1.206, 95% =
      CI 1.035-1.405, p = 0.016; CC vs. TC/TT: OR = 1.254, 95% CI = 1.077-1.461, p =
      0.004), with the exception of the TC-versus-TT model (TC vs. TT: OR = 1.130, 95%
      CI = 0.961-1.329, p = 0.138). In a subgroup analysis based on ethnicity, we
      identified a significant overrepresentation of the polymorphism in individuals of
      Asian ethnicity. CONCLUSION: This meta-analysis indicates a significant
      association between the miRNA-196a2 polymorphism and CRC risk.

PMID- 24107910
TI  - Overexpression of CD40 in sacral chordomas and its correlation with low tumor
      recurrence.
AB  - AIM: To determine the degree of CD40 overexpression in sacral chordomas and its
      correlation with tumor recurrence. METHODS: CD40 or CD31 overexpression was
      determined by immunohistochemical staining; the microvessel density (MVD) was
      calculated according to the CD31 expression. The correlation of CD40 over
      expression with tumor recurrence was analyzed. RESULTS: 56% of the specimens from
      36 cases of sacral chordomas overexpressed CD40, which is a significantly higher
      percentage than for the 2 specimens in 10 in normal notochordal tissue (p <
      0.05). 36.84% of the specimens of the 19 recurrent cases were CD40
      overexpressing, in contrast to less than 76.47% in the no-recurrence group (p <
      0.05). Multivariate analysis demonstrated that CD40 overexpression and the
      resection margins were independent factors contributing to tumor recurrence. The
      MVD value was 25.71 +/- 8.86 mm(-2) in the sacral chordomas and more than 6.63 +/
      2.45 mm(-2) in the normal embryonic notochord tissue (p < 0.01). The MVD value
      in the recurrence group (30.08 +/- 7.11 mm(-2)) was significantly higher than
      that of the no-recurrence group (20.82 +/- 8.18 mm(-2); p < 0.05). But the MVD
      value was significantly lower in the CD40-overexpressing group than in the CD40
      less expressing group (p < 0.05). CONCLUSIONS: CD40 was overexpressed in sacral
      chordomas, and the overexpression was not dependent on the intratumoral MVD. CD40
      overexpression was correlated with low recurrence of the tumor, implying that
      CD40 plays an important role in the antitumor response against sacral chordomas
      and in the inhibition of tumor recurrence.

PMID- 24107911
TI  - Association of the hsa-mir-499 (rs3746444) polymorphisms with gastric cancer risk
      in the Chinese population.
AB  - BACKGROUND: Single-nucleotide polymorphisms (SNPs) in microRNAs (miRNA) have been
      shown to be related with susceptibility to several human cancers. We evaluated
      the associations of rs3746444 in pre-miRNA hsa-mir-499 with the risk of gastric
      cancer (GC) in the Chinese population. PATIENTS AND METHODS: The rs3746444 (A>G)
      SNPs were genotyped in 201 GC and 213 non-cancer subjects in a case-control study
      by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP)
      analysis. RESULTS: There was no significant overall difference in the genotype
      distributions of rs3746444 (A>G) SNPs between cases and controls. In the logistic
      regression analyses, no significantly increased risk of GC was found to be
      associated with variant genotypes. CONCLUSION: The rs3746444 (A>G) SNP is not
      associated with susceptibility to GC in the Chinese population.

PMID- 24107912
TI  - Serum S100B levels correlate with clinical benefit in a metastatic melanoma
      patient treated by CTLA-4 blockade: a case report.
AB  - BACKGROUND: Cytotoxic T lymphocyte-associated antigen-4 (CTLA-4) is an
      immunoregulatory molecule expressed by activated T cells. In patients with
      metastatic melanoma, anti-CTLA-4 antibody therapy with ipilimumab achieves
      durable cancer regression in approximately 10-15% of patients. In the face of
      complex and sometimes delayed tumor response patterns, prognostic and predictive
      biomarkers are needed to monitor therapy outcomes and to identify early potential
      long-term survivors who might also benefit from therapy re-induction. CASE
      REPORT: The clinical case of a 49-year-old male patient with metastatic melanoma
      and unfavorable prognostic factors is presented. The time course of the serum
      biomarker S100B during initial anti-CTLA-4 therapy correlated very well with the
      clinical situation and, in the present case, proved its potential value as an
      early biomarker of a subsequently observed radiological response in this stage IV
      melanoma patient. The observed clinical response lasted for more than 24 months.
      CONCLUSIONS: Further efforts are required to better understand the patterns of
      response and the immunological tumor response in patients undergoing CTLA-4
      blockade. A validation of S100B as a marker to identify early long-term
      responders among patients treated with ipilimumab is warranted.

PMID- 24107913
TI  - Coinfection of Pneumocystis jirovecii and invasive pulmonary aspergillosis in an
      immunocompromised patient: a diagnostic challenge.
AB  - BACKGROUND: Invasive infections caused by Aspergillus fumigatus as well as
      Pneumocystis pneumonia are serious and often lethal diseases in severely
      immunocompromised patients. CASE REPORT: We report on a rare case of a pulmonary
      coinfection of Pneumocystis jirovecii and Aspergillus fumigatus in a 59-year-old
      female patient with a history of astrocytoma treated with high doses of
      corticosteroids and a subsequent CD4 lymphocyte count of 30/ul. CONCLUSION: A
      heightened clinical awareness and a stringent and accurate diagnostic work-up
      encompassing diagnostic tools to detect even coincident fungal infections is
      crucial for sufficient and early antifungal treatment in immunocompromised
      patients with lung infiltrates.

PMID- 24107914
TI  - Concomitant chemoradiotherapy and antiretroviral therapy for HIV-infected
      patients with locoregionally advanced non-small cell lung cancer: benefit and
      tolerability of treatment in 2 cases.
AB  - BACKGROUND: Human immunodeficiency virus (HIV)-infected patients are surviving
      longer since the advent of antiretroviral therapy. Therefore, more patients are
      developing non-AIDS-defining cancers which increasingly determine mortality. CASE
      REPORTS: Here we present 2 cases of locally advanced non-small cell lung cancer
      treated initially with concomitant chemoradiotherapy and antiretroviral therapy.
      Both patients were male, ages 69 and 66, with known HIV infection and
      immunologically stable on antiretroviral therapy. Presenting symptoms included
      superior sulcus tumor with left arm immobility and sensory disturbance in case 1
      and right lower bronchus constriction in case 2. Symptoms were controlled by
      chemoradiotherapy. CONCLUSION: These cases illustrate that intensive anticancer
      therapy administered to the HIV-infected population can be tolerated even though
      these patients seem to be too fragile for both chemotherapy and radiotherapy,
      especially since the potential benefit remains uncertain. Recent improvements in
      chemoradiotherapy and supportive care have enhanced tolerance for such therapy.

PMID- 24107915
TI  - Ubiquitin-proteasome pathway and prostate cancer.
AB  - Prostate cancer is one of the most common cancers in men. Various signaling
      pathways and proteins are involved in prostate carcinogenesis. Ubiquitination and
      deubiquitination of the related proteins contribute to the development of
      prostate cancer in various ways. The ubiquitin-proteasome (UPS) system is a
      common cellular process for protein degradation in eukaryotes. In this article we
      review recent advances related to the involvement of the UPS pathway in prostate
      cancer. The UPS pathway plays an important role in the regulation of cellular
      proteins with respect to cell cycle control, transcription, apoptosis, cell
      adhesion, angiogenesis, and tumor growth. It is involved in prostate cancer in
      various ways by modulating prostate cancer-related genes/proteins such as
      androgen receptor, cyclin-dependent kinase inhibitor P27, cyclin D1, and PTEN.
      Some ubiquitin-like modifier proteins have also been found to be associated with
      prostate cancer. The UPS pathway represents a potential therapeutic target for
      prostate cancer, and proteasome inhibitors represent a class of chemotherapeutic
      agents that inhibit tumor growth. The UPS pathway is related to prostate cancer
      in different ways. More research on that link is needed, as targeting the UPS
      pathway has led to some success in prostate cancer treatment.

PMID- 24107916
TI  - PPARgamma against tumors by different signaling pathways.
AB  - The peroxisome proliferator-activated receptor-gamma (PPARgamma) belongs to the
      nuclear hormone receptor superfamily, and is expressed in adipose tissue,
      skeletal muscle, spleen, heart, liver, placenta, lung, and ovary. PPARgamma is a
      critical regulator of inflammation, adipocyte differentiation, glucose
      homeostasis, and tumorigenesis. The mechanism of PPARgamma on tumor suppression
      is still unclear, but plenty of evidence shows that PPARgamma provides new
      therapeutic targets for cancer. Here we give a review of how PPARgamma and its
      ligands regulate tumorigenesis by different pathways.

PMID- 24107917
TI  - "Clickable" LNA/DNA probes for fluorescence sensing of nucleic acids and
      autoimmune antibodies.
AB  - Herein we describe fluorescent oligonucleotides prepared by click chemistry
      between novel alkyne-modified locked nucleic acid (LNA) strands and a series of
      fluorescent azides for homogeneous (all-in-solution) detection of nucleic acids
      and autoimmune antibodies. 

PMID- 24107919
TI  - Integrate and fire pulse train automaton for QRS detection.
AB  - Monitoring heart activity from electrocardiograms (ECG) is crucial to avoid
      unnecessary fatalities; therefore, detection of QRS complex is fundamental to
      automated ECG monitoring. Continuous, portable 24/7 ECG monitoring requires
      wireless technology with constraints on power, bandwidth, area, and resolution.
      In order to provide continuous remote monitoring of patients and fast
      transmission of data to medical personnel for instantaneous intervention, we
      propose a methodology that converts analog inputs into pulses for ultralow power
      implementation. The signal encoding scheme is the time-based integrate and fire
      (IF) sampler from which a set of signal descriptors in the pulse domain are
      proposed. Furthermore, a logical decision rule for QRS detection based on
      morphological checking is derived. The proposed decision logic depends
      exclusively on relational and logical operators resulting in ultrafast
      recognition and can be implemented using combinatorial logic hardware to
      guarantee power consumption orders of magnitude lower than any microprocessor
      device. The algorithm was evaluated using the MIT-BIH arrhythmia database and
      results show that our algorithm performance is comparable to the state-of-the art
      software-based detection.

PMID- 24107918
TI  - Creation and characterization of an ultrasound and CT phantom for noninvasive
      ultrasound thermometry calibration.
AB  - Ultrasound thermometry provides noninvasive 2-D temperature monitoring, and in
      this paper, we have investigated the use of computed tomography (CT) radiodensity
      to characterize tissues to improve the accuracy of ultrasound thermometry.
      Agarose-based tissue-mimicking phantoms were created with glyceryl trioleate (a
      fat-mimicking material) concentration of 0%, 10%, 20%, 30%, 40%, and 50%. The
      speed of sound (SOS) of the phantoms was measured over a temperature range of
      22.1-41.1  degrees C. CT images of the phantoms were acquired by a clinical
      dedicated breast CT scanner, followed by calculation of the Hounsfield units
      (HU). The phantom was heated with a therapeutic acoustic pulse (1.54 MHz), while
      RF data were acquired with a 10-MHz linear-array transducer. Two-dimensional
      speckle tracking was used to calculate the thermal strain offline. The tissue
      dependent thermal strain parameter required for ultrasound thermometry was
      analyzed and correlated with CT radiodensity, followed by the validation of the
      temperature prediction. Results showed that the change in SOS with the
      temperature increase was opposite in sign between the 0%-10% and 20%-50%
      trioleate phantoms. The inverse of the tissue-dependent thermal strain parameter
      of the phantoms was correlated with the CT radiodensity (R(2) = 0.99). A blinded
      ultrasound thermometry study on phantoms with a trioleate range of 5%-35%
      demonstrated the capability to estimate the tissue-dependent thermal strain
      parameter and estimate temperature with error less than ~1  degrees C. In
      conclusion, CT radiodensity may provide a method for improving ultrasound
      thermometry in heterogeneous tissues. 

PMID- 24107920
TI  - Heterogeneous and multiphase formation pathways of gypsum in the atmosphere.
AB  - Gypsum is a major sulphur-containing component of atmospheric particulate matter.
      To date, however, its formation pathways in the atmosphere are still not well
      known. In this study, several potentially important formation pathways of gypsum
      in atmospheric aerosols are proposed. We found that gypsum was formed in the
      humidifying-dehumidifying process of mixed sulphate and calcium salts. A
      deliquescent layer is crucial for the formation of gypsum from Ca(2+) and SO4(2-)
      ions. In particular, the presence of hygroscopic components, such as (NH4)2SO4
      and Ca(NO3)2, is necessary for the conversion of calcium carbonate (CaCO3) upon
      heterogeneous reaction of either SO2 + O3 or SO2 + NO2 as well as anhydrous
      calcium sulphate (CaSO4) to form gypsum (CaSO4.2H2O) under ambient conditions.
      This study provides definitive evidence that synergistic effects in the physical
      and chemical processing of aerosol particles have a significant effect on their
      final chemical composition, mixing state and hygroscopic behaviour which dictates
      the environmental and climate impacts of the resulting aerosol. 

PMID- 24107922
TI  - Growing metal nanoparticles in superfluid helium.
AB  - Helium droplets provide a cold and confined environment where atomic and/or
      molecular dopants can aggregate into clusters and nanoparticles. In particular,
      the sequential addition of different materials to helium droplets can lead to the
      formation of a wide range of nanoparticles, including core-shell nanoparticles,
      which can then be deposited onto a surface. Here we briefly discuss the
      fundamental properties of helium droplets and then address their implications for
      the formation of clusters and nanoparticles. Several key experiments on atomic
      and molecular clusters will be highlighted and new results obtained for
      nanoparticles formed in this way will be presented. Finally, the versatility, the
      limitations and new possibilities provided by superfluid helium droplets in
      nanoscience and nanotechnology will be addressed. 

PMID- 24107923
TI  - Synthesis, characterisation, and oxygen atom transfer reactions involving the
      first gold(I)-alkylperoxo complexes.
AB  - The synthesis of a new class of organogold species containing a peroxo moiety is
      reported. Complexes [Au(IPr)(OO(t)Bu)] and [Au(SIPr)(OO(t)Bu)] have been
      synthesised via a straightforward methodology using the parent gold(I) hydroxide
      complexes as synthons. These complexes have been successfully used in oxygen
      transfer reactions to triphenylphosphine.

PMID- 24107921
TI  - The STIM1/Orai signaling machinery.
AB  - Ca(2+) influx via store-operated Ca(2+) release activated Ca(2+) (CRAC) channels
      represents a main signaling pathway for T-cell activation as well as mast-cell
      degranulation. The ER-located Ca(2+)-sensor, STIM1 and the Ca(2+)-selective ion
      pore, Orai1 in the membrane are sufficient to fully reconstitute CRAC currents.
      Their identification, but even more the recent structural resolution of both
      proteins by X-ray crystallography has substantially advanced the understanding of
      the activation mechanism of CRAC channels. In this review, we provide a detailed
      description of the STIM1/Orai1 signaling pathway thereby focusing on the critical
      domains mediating both, intra- as well as intermolecular interactions and on the
      ion permeation pathway. Based on the results of functional studies as well as the
      recently published crystal structures, we portray a mechanistic view of the steps
      in the CRAC channel signaling cascade ranging from STIM1 oligomerization over
      STIM1-Orai1 coupling to the ultimate Orai1 channel activation and permeation.

PMID- 24107924
TI  - Interactive Hierarchical-Flow Segmentation of Scar Tissue From Late-Enhancement
      Cardiac MR Images.
AB  - We propose a novel multi-region image segmentation approach to extract myocardial
      scar tissue from 3-D whole-heart cardiac late-enhancement magnetic resonance
      images in an interactive manner. For this purpose, we developed a graphical user
      interface to initialize a fast max-flow-based segmentation algorithm and segment
      scar accurately with progressive interaction. We propose a partially-ordered
      Potts (POP) model to multi-region segmentation to properly encode the known
      spatial consistency of cardiac regions. Its generalization introduces a custom
      label/region order constraint to Potts model to multi-region segmentation. The
      combinatorial optimization problem associated with the proposed POP model is
      solved by means of convex relaxation, for which a novel multi-level continuous
      max-flow formulation, i.e., the hierarchical continuous max-flow (HMF) model, is
      proposed and studied. We demonstrate that the proposed HMF model is dual or
      equivalent to the convex relaxed POP model and introduces a new and efficient
      hierarchical continuous max-flow based algorithm by modern convex optimization
      theory. In practice, the introduced hierarchical continuous max-flow based
      algorithm can be implemented on the parallel GPU to achieve significant
      acceleration in numerics. Experiments are performed in 50 whole heart 3-D LE
      datasets, 35 with left-ventricular and 15 with right-ventricular scar. The
      experimental results are compared to full-width-at-half-maximum and Signal
      threshold to reference-mean methods using manual expert myocardial segmentations
      and operator variabilities and the effect of user interaction are assessed. The
      results indicate a substantial reduction in image processing time with robust
      accuracy for detection of myocardial scar. This is achieved without the need for
      additional region constraints and using a single optimization procedure,
      substantially reducing the potential for error. 

PMID- 24107925
TI  - Visual SLAM for Handheld Monocular Endoscope.
AB  - Simultaneous localization and mapping (SLAM) methods provide real-time estimation
      of 3-D models from the sole input of a handheld camera, routinely in mobile
      robotics scenarios. Medical endoscopic sequences mimic a robotic scenario in
      which a handheld camera (monocular endoscope) moves along an unknown trajectory
      while observing an unknown cavity. However, the feasibility and accuracy of SLAM
      methods have not been extensively validated with human in vivo image sequences.
      In this work, we propose a monocular visual SLAM algorithm tailored to deal with
      medical image sequences in order to provide an up-to-scale 3-D map of the
      observed cavity and the endoscope trajectory at frame rate. The algorithm is
      validated over synthetic data and human in vivo sequences corresponding to 15
      laparoscopic hernioplasties where accurate ground-truth distances are available.
      It can be concluded that the proposed procedure is: 1) noninvasive, because only
      a standard monocular endoscope and a surgical tool are used; 2) convenient,
      because only a hand-controlled exploratory motion is needed; 3) fast, because the
      algorithm provides the 3-D map and the trajectory in real time; 4) accurate,
      because it has been validated with respect to ground-truth; and 5) robust to
      inter-patient variability, because it has performed successfully over the
      validation sequences. 

PMID- 24107926
TI  - A Mechanics-Based Nonrigid Registration Method for Liver Surgery Using Sparse
      Intraoperative Data.
AB  - In open abdominal image-guided liver surgery, sparse measurements of the organ
      surface can be taken intraoperatively via a laser-range scanning device or a
      tracked stylus with relatively little impact on surgical workflow. We propose a
      novel nonrigid registration method which uses sparse surface data to reconstruct
      a mapping between the preoperative CT volume and the intraoperative patient
      space. The mapping is generated using a tissue mechanics model subject to
      boundary conditions consistent with surgical supportive packing during liver
      resection therapy. Our approach iteratively chooses parameters which define these
      boundary conditions such that the deformed tissue model best fits the
      intraoperative surface data. Using two liver phantoms, we gathered a total of
      five deformation datasets with conditions comparable to open surgery. The
      proposed nonrigid method achieved a mean target registration error (TRE) of 3.3
      mm for targets dispersed throughout the phantom volume, using a limited region of
      surface data to drive the nonrigid registration algorithm, while rigid
      registration resulted in a mean TRE of 9.5 mm. In addition, we studied the effect
      of surface data extent, the inclusion of subsurface data, the trade-offs of using
      a nonlinear tissue model, robustness to rigid misalignments, and the feasibility
      in five clinical datasets. 

PMID- 24107927
TI  - Response to "A case of 5-FU-related severe toxicity associated with the P.Y186C
      DPYD variant".

PMID- 24107928
TI  - Interaction of the efflux transporters ABCB1 and ABCG2 with imatinib, nilotinib,
      and dasatinib.
AB  - The efflux transporters adenosine triphosphate (ATP)-binding cassette (ABC)B1 and
      ABCG2 have been demonstrated to interact with the tyrosine kinase inhibitors
      (TKIs) imatinib, nilotinib, and dasatinib. However, although some studies
      conclude that TKIs are substrates of one or both transporters, other studies
      demonstrate only an inhibitory function. This variation is probably due to
      differences in the concentration of TKIs assayed and the experimental systems
      used. This article examines the evidence for clinically relevant interactions
      between three currently approved TKIs and ABCB1/ABCG2. 

PMID- 24107930
TI  - Diagnostic accuracy of 64-slice multidetector CT angiography for detection of in
      stent restenosis of vertebral artery ostium stents: comparison with conventional
      angiography.
AB  - BACKGROUND: There are very few reports assessing in-stent restenosis (ISR) after
      vertebral artery ostium (VAO) stents using multidetector computed tomography
      (MDCT). PURPOSE: To compare the diagnostic accuracy of computed tomography
      angiography (CTA) using 64-slice MDCT with digital subtraction angiography (DSA)
      for detection of significant ISR after VAO stenting. MATERIAL AND METHODS: The
      study evaluated 57 VAO stents in 57 patients (39 men, 18 women; mean age 64 years
      [range, 48-90 years]). All stents were scanned with a 64-slice MDCT scanner.
      Three sets of images were reconstructed with three different convolution kernels.
      Two observers who were blinded to the results of DSA assessed the diagnostic
      accuracy of CTA for detecting significant ISR (>=50% diameter narrowing) of VAO
      stents in comparison with DSA as the reference standard. The sensitivity,
      specificity, positive and negative predictive values, and accuracy were
      calculated. RESULTS: Of the 57 stents, 46 (81%) were assessable using CTA, while
      11 (19%) were not. No stents with diameters <=2.75 mm were assessable. DSA
      revealed 13 cases of significant ISR in all stents. The respective sensitivity,
      specificity, positive and negative predictive values, and accuracy were 92%, 82%,
      60%, 97%, and 84% for all stents. On excluding the 11 non-assessable stents, the
      respective values were 88%, 95%, 78%, 97%, and 93%. Of the 46 CTA assessable
      stents, eight significant ISRs were diagnosed on DSA. Seven of eight patients
      with significant ISR by DSA were diagnosed correctly with CTA. The area under the
      receiver-operating characteristic curve (AUC) was 0.87 for all stents and 0.91
      for assessable stents, indicating good to excellent agreement between CTA and DSA
      for detecting significant ISR after VAO stenting. CONCLUSION: Sixty-four-slice
      MDCT is a promising non-invasive method of assessing stent patency and can
      exclude significant ISR with high diagnostic values after VAO stenting.

PMID- 24107931
TI  - Measurement of muscle architecture concurrently with muscle hardness using
      ultrasound strain elastography.
AB  - BACKGROUND: The B-mode ultrasound image that can measure muscle architecture is
      displayed side by side with the ultrasound strain elastogram that can assess
      muscle hardness. Consequently, muscle architecture can be measured concurrently
      with muscle hardness using ultrasound strain elastography. PURPOSE: To
      demonstrate the measurement of muscle architecture concurrently with muscle
      hardness using ultrasound strain elastography. MATERIAL AND METHODS: Concurrent
      measurements of muscle architectural parameters (muscle thickness, pennation
      angle, and fascicle length) and muscle hardness of the medial gastrocnemius were
      performed with ultrasound strain elastography. Separate measurements of the
      muscle architectural parameters were also performed for use as reference values
      for the concurrent measurements. Both types of measurements were performed twice
      at 20 degrees  dorsiflexion, neutral position, and 30 degrees  plantar flexion.
      RESULTS: Coefficients of variance of the muscle architectural parameters obtained
      from the concurrent measurements (<=7.6%) were significantly higher than those
      obtained from the separate measurements (<=2.4%) (all P < 0.05). Intraclass
      correlation coefficients of the architectural parameters were lower in the
      concurrent measurements (>=0.74) than in the separate measurements (>=0.97).
      However, there were no significant differences in any muscle architectural
      parameters between the concurrent and separate measurements (all P > 0.05).
      CONCLUSION: The use of ultrasound strain elastography for the concurrent
      measurement of muscle architecture and muscle hardness is feasible.

PMID- 24107932
TI  - Half-sandwich bis(propiolamidinate) rare-earth metal complexes: synthesis,
      structure and dissociation of the cyclopentadienyl ligand via competition with an
      amidinate.
AB  - A comparative study on the stabilizing ability between C5Me4(SiMe3) (Cp' for
      short) and amidinate in rare-earth metal complexes is investigated. Cp' is found
      to dissociate from half-sandwich bis(propiolamidinate) lanthanides via
      competition with a propiolamidinate, which clearly shows that the coordinative
      ability of chelate amidinate is stronger than that of eta(5)-Cp' under the
      present conditions.

PMID- 24107933
TI  - Saliency-aware video compression.
AB  - In region-of-interest (ROI)-based video coding, ROI parts of the frame are
      encoded with higher quality than non-ROI parts. At low bit rates, such encoding
      may produce attention-grabbing coding artifacts, which may draw viewer's
      attention away from ROI, thereby degrading visual quality. In this paper, we
      present a saliency-aware video compression method for ROI-based video coding. The
      proposed method aims at reducing salient coding artifacts in non-ROI parts of the
      frame in order to keep user's attention on ROI. Further, the method allows
      saliency to increase in high quality parts of the frame, and allows saliency to
      reduce in non-ROI parts. Experimental results indicate that the proposed method
      is able to improve visual quality of encoded video relative to conventional rate
      distortion optimized video coding, as well as two state-of-the art perceptual
      video coding methods. 

PMID- 24107934
TI  - A novel approach for lung nodules segmentation in chest CT using level sets.
AB  - A new variational level set approach is proposed for lung nodule segmentation in
      lung CT scans. A general lung nodule shape model is proposed using implicit
      spaces as a signed distance function. The shape model is fused with the image
      intensity statistical information in a variational segmentation framework. The
      nodule shape model is mapped to the image domain by a global transformation that
      includes inhomogeneous scales, rotation, and translation parameters. A matching
      criteria between the shape model and the image implicit representations is
      employed to handle the alignment process. Transformation parameters evolve
      through gradient descent optimization to handle the shape alignment process and
      hence mark the boundaries of the nodule "head." The embedding process takes into
      consideration the image intensity as well as prior shape information. A
      nonparametric density estimation approach is employed to handle the statistical
      intensity representation of the nodule and background regions. The proposed
      technique does not depend on nodule type or location. Exhaustive experimental and
      validation results are demonstrated on 742 nodules obtained from four different
      CT lung databases, illustrating the robustness of the approach.

PMID- 24107935
TI  - Fenchel duality based dictionary learning for restoration of noisy images.
AB  - Dictionary learning based sparse modeling has been increasingly recognized as
      providing high performance in the restoration of noisy images. Although a number
      of dictionary learning algorithms have been developed, most of them attack this
      learning problem in its primal form, with little effort being devoted to
      exploring the advantage of solving this problem in a dual space. In this paper, a
      novel Fenchel duality based dictionary learning (FD-DL) algorithm has been
      proposed for the restoration of noise-corrupted images. With the restricted
      attention to the additive white Gaussian noise, the sparse image representation
      is formulated as an 2-1 minimization problem, whose dual formulation is
      constructed using a generalization of Fenchel's duality theorem and solved under
      the augmented Lagrangian framework. The proposed algorithm has been compared with
      four state-of-the-art algorithms, including the local pixel grouping-principal
      component analysis, method of optimal directions, K-singular value decomposition,
      and beta process factor analysis, on grayscale natural images. Our results
      demonstrate that the FD-DL algorithm can effectively improve the image quality
      and its noisy image restoration ability is comparable or even superior to the
      abilities of the other four widely-used algorithms.

PMID- 24107936
TI  - Image set based face recognition using self-regularized non-negative coding and
      adaptive distance metric learning.
AB  - Simple nearest neighbor classification fails to exploit the additional
      information in image sets. We propose self-regularized nonnegative coding to
      define between set distance for robust face recognition. Set distance is measured
      between the nearest set points (samples) that can be approximated from their
      orthogonal basis vectors as well as from the set samples under the respective
      constraints of self-regularization and nonnegativity. Self-regularization
      constrains the orthogonal basis vectors to be similar to the approximated nearest
      point. The nonnegativity constraint ensures that each nearest point is
      approximated from a positive linear combination of the set samples. Both
      constraints are formulated as a single convex optimization problem and the
      accelerated proximal gradient method with linear-time Euclidean projection is
      adapted to efficiently find the optimal nearest points between two image sets.
      Using the nearest points between a query set and all the gallery sets as well as
      the active samples used to approximate them, we learn a more discriminative
      Mahalanobis distance for robust face recognition. The proposed algorithm works
      independently of the chosen features and has been tested on gray pixel values and
      local binary patterns. Experiments on three standard data sets show that the
      proposed method consistently outperforms existing state-of-the-art methods.

PMID- 24107937
TI  - Multiplexed biomimetic lipid membranes on graphene by dip-pen nanolithography.
AB  - The application of graphene in sensor devices depends on the ability to
      appropriately functionalize the pristine graphene. Here we show the direct
      writing of tailored phospholipid membranes on graphene using dip-pen
      nanolithography. Phospholipids exhibit higher mobility on graphene compared with
      the commonly used silicon dioxide substrate, leading to well-spread uniform
      membranes. Dip-pen nanolithography allows for multiplexed assembly of
      phospholipid membranes of different functionalities in close proximity to each
      other. The membranes are stable in aqueous environments and we observe electronic
      doping of graphene by charged phospholipids. On the basis of these results, we
      propose phospholipid membranes as a route for non-covalent immobilization of
      various functional groups on graphene for applications in biosensing and
      biocatalysis. As a proof of principle, we demonstrate the specific binding of
      streptavidin to biotin-functionalized membranes. The combination of atomic force
      microscopy and binding experiments yields a consistent model for the layer
      organization within phospholipid stacks on graphene. 

PMID- 24107938
TI  - TASK-2 channels contribute to pH sensitivity of retrotrapezoid nucleus
      chemoreceptor neurons.
AB  - Phox2b-expressing glutamatergic neurons of the retrotrapezoid nucleus (RTN)
      display properties expected of central respiratory chemoreceptors; they are
      directly activated by CO2/H(+) via an unidentified pH-sensitive background K(+)
      channel and, in turn, facilitate brainstem networks that control breathing. Here,
      we used a knock-out mouse model to examine whether TASK-2 (K2P5), an alkaline
      activated background K(+) channel, contributes to RTN neuronal pH sensitivity. We
      made patch-clamp recordings in brainstem slices from RTN neurons that were
      identified by expression of GFP (directed by the Phox2b promoter) or beta
      galactosidase (from the gene trap used for TASK-2 knock-out). Whereas nearly all
      RTN cells from control mice were pH sensitive (95%, n = 58 of 61), only 56% of
      GFP-expressing RTN neurons from TASK-2(-/-) mice (n = 49 of 88) could be
      classified as pH sensitive (>30% reduction in firing rate from pH 7.0 to pH 7.8);
      the remaining cells were pH insensitive (44%). Moreover, none of the recorded RTN
      neurons from TASK-2(-/-) mice selected based on beta-galactosidase activity (a
      subpopulation of GFP-expressing neurons) were pH sensitive. The alkaline
      activated background K(+) currents were reduced in amplitude in RTN neurons from
      TASK-2(-/-) mice that retained some pH sensitivity but were absent from pH
      insensitive cells. Finally, using a working heart-brainstem preparation, we found
      diminished inhibition of phrenic burst amplitude by alkalization in TASK-2(-/-)
      mice, with apneic threshold shifted to higher pH levels. In conclusion, alkaline
      activated TASK-2 channels contribute to pH sensitivity in RTN neurons, with
      effects on respiration in situ that are particularly prominent near apneic
      threshold. 

PMID- 24107939
TI  - NaV1.1 channels in axon initial segments of bipolar cells augment input to
      magnocellular visual pathways in the primate retina.
AB  - In the primate visual system, the ganglion cells of the magnocellular pathway
      underlie motion and flicker detection and are relatively transient, while the
      more sustained ganglion cells of the parvocellular pathway have comparatively
      lower temporal resolution, but encode higher spatial frequencies. Although it is
      presumed that functional differences in bipolar cells contribute to the tuning of
      the two pathways, the properties of the relevant bipolar cells have not yet been
      examined in detail. Here, by making patch-clamp recordings in acute slices of
      macaque retina, we show that the bipolar cells within the magnocellular pathway,
      but not the parvocellular pathway, exhibit voltage-gated sodium (NaV), T-type
      calcium (CaV), and hyperpolarization-activated, cyclic nucleotide-gated (HCN)
      currents, and can generate action potentials. Using immunohistochemistry in
      macaque and human retinae, we show that NaV1.1 is concentrated in an axon initial
      segment (AIS)-like region of magnocellular pathway bipolar cells, a
      specialization not seen in transient bipolar cells of other vertebrates. In
      contrast, CaV3.1 channels were localized to the somatodendritic compartment and
      proximal axon, but were excluded from the AIS, while HCN1 channels were
      concentrated in the axon terminal boutons. Simulations using a compartmental
      model reproduced physiological results and indicate that magnocellular pathway
      bipolar cells initiate spikes in the AIS. Finally, we demonstrate that NaV
      channels in bipolar cells augment excitatory input to parasol ganglion cells of
      the magnocellular pathway. Overall, the results demonstrate that selective
      expression of voltage-gated channels contributes to the establishment of parallel
      processing in the major visual pathways of the primate retina. 

PMID- 24107940
TI  - Learning-related translocation of delta-opioid receptors on ventral striatal
      cholinergic interneurons mediates choice between goal-directed actions.
AB  - The ability of animals to extract predictive information from the environment to
      inform their future actions is a critical component of decision-making. This
      phenomenon is studied in the laboratory using the pavlovian-instrumental transfer
      protocol in which a stimulus predicting a specific pavlovian outcome biases
      choice toward those actions earning the predicted outcome. It is well established
      that this transfer effect is mediated by corticolimbic afferents on the nucleus
      accumbens shell (NAc-S), and recent evidence suggests that delta-opioid receptors
      (DORs) play an essential role in this effect. In DOR-eGFP knock-in mice, we show
      a persistent, learning-related plasticity in the translocation of DORs to the
      somatic plasma membrane of cholinergic interneurons (CINs) in the NAc-S during
      the encoding of the specific stimulus-outcome associations essential for
      pavlovian-instrumental transfer. We found that increased membrane DOR expression
      reflected both stimulus-based predictions of reward and the degree to which these
      stimuli biased choice during the pavlovian-instrumental transfer test.
      Furthermore, this plasticity altered the firing pattern of CINs increasing the
      variance of action potential activity, an effect that was exaggerated by DOR
      stimulation. The relationship between the induction of membrane DOR expression in
      CINs and both pavlovian conditioning and pavlovian-instrumental transfer provides
      a highly specific function for DOR-related modulation in the NAc-S, and it is
      consistent with an emerging role for striatal CIN activity in the processing of
      predictive information. Therefore, our results reveal evidence of a long-term,
      experience-dependent plasticity in opioid receptor expression on striatal
      modulatory interneurons critical for the cognitive control of action. 

PMID- 24107941
TI  - Plant sterols the better cholesterol in Alzheimer's disease? A mechanistical
      study.
AB  - Amyloid-beta (Abeta), major constituent of senile plaques in Alzheimer's disease
      (AD), is generated by proteolytic processing of the amyloid precursor protein
      (APP) by beta- and gamma-secretase. Several lipids, especially cholesterol, are
      associated with AD. Phytosterols are naturally occurring cholesterol plant
      equivalents, recently been shown to cross the blood-brain-barrier accumulating in
      brain. Here, we investigated the effect of the most nutritional prevalent
      phytosterols and cholesterol on APP processing. In general, phytosterols are less
      amyloidogenic than cholesterol. However, only one phytosterol, stigmasterol,
      reduced Abeta generation by (1) directly decreasing beta-secretase activity, (2)
      reducing expression of all gamma-secretase components, (3) reducing cholesterol
      and presenilin distribution in lipid rafts implicated in amyloidogenic APP
      cleavage, and by (4) decreasing BACE1 internalization to endosomal compartments,
      involved in APP beta-secretase cleavage. Mice fed with stigmasterol-enriched
      diets confirmed protective effects in vivo, suggesting that dietary intake of
      phytosterol blends mainly containing stigmasterol might be beneficial in
      preventing AD. 

PMID- 24107942
TI  - Essential role of SIRT1 signaling in the nucleus accumbens in cocaine and
      morphine action.
AB  - Sirtuins (SIRTs), class III histone deacetylases, are well characterized for
      their control of cellular physiology in peripheral tissues, but their influence
      in brain under normal and pathological conditions remains poorly understood.
      Here, we establish an essential role for SIRT1 and SIRT2 in regulating behavioral
      responses to cocaine and morphine through actions in the nucleus accumbens (NAc),
      a key brain reward region. We show that chronic cocaine administration increases
      SIRT1 and SIRT2 expression in the mouse NAc, while chronic morphine
      administration induces SIRT1 expression alone, with no regulation of all other
      sirtuin family members observed. Drug induction of SIRT1 and SIRT2 is mediated in
      part at the transcriptional level via the drug-induced transcription factor
      DeltaFosB and is associated with robust histone modifications at the Sirt1 and
      Sirt2 genes. Viral-mediated overexpression of SIRT1 or SIRT2 in the NAc enhances
      the rewarding effects of both cocaine and morphine. In contrast, the local
      knockdown of SIRT1 from the NAc of floxed Sirt1 mice decreases drug reward. Such
      behavioral effects of SIRT1 occur in concert with its regulation of numerous
      synaptic proteins in NAc as well as with SIRT1-mediated induction of dendritic
      spines on NAc medium spiny neurons. These studies establish sirtuins as key
      mediators of the molecular and cellular plasticity induced by drugs of abuse in
      NAc, and of the associated behavioral adaptations, and point toward novel
      signaling pathways involved in drug action. 

PMID- 24107944
TI  - What does motor efference copy represent? Evidence from speech production.
AB  - How precisely does the brain predict the sensory consequences of our actions?
      Efference copy is thought to reflect the predicted sensation of self-produced
      motor acts, such as the auditory feedback heard while speaking. Here, we use
      magnetoencephalographic imaging (MEG-I) in human speakers to demonstrate that
      efference copy prediction does not track movement variability across repetitions
      of the same motor task. Specifically, spoken vowels were less accurately
      predicted when they were less similar to a speaker's median production, even
      though the prediction is thought to be based on the very motor commands that
      generate each vowel. Auditory cortical responses to less prototypical speech
      productions were less suppressed, resembling responses to speech errors, and were
      correlated with later corrective movement, suggesting that the suppression may be
      functionally significant for error correction. The failure of the motor system to
      accurately predict less prototypical speech productions suggests that the
      efferent-driven suppression does not reflect a sensory prediction, but a sensory
      goal. 

PMID- 24107943
TI  - Dissociable neural mechanisms for goal-directed versus incidental memory
      reactivation.
AB  - Remembering a past event involves reactivation of distributed patterns of neural
      activity that represent the features of that event-a process that depends on
      associative mechanisms supported by medial temporal lobe structures. Although
      efficient use of memory requires prioritizing those features of a memory that are
      relevant to current behavioral goals (target features) over features that may be
      goal-irrelevant (incidental features), there remains ambiguity concerning how
      this is achieved. We tested the hypothesis that although medial temporal lobe
      structures may support reactivation of both target and incidental event features,
      frontoparietal cortex preferentially reactivates those features that match
      current goals. Here, human participants were cued to remember either the category
      (face/scene) to which a picture belonged (category trials) or the location
      (left/right) in which a picture appeared (location trials). Multivoxel pattern
      analysis of fMRI data were used to measure reactivation of category information
      as a function of its behavioral relevance (target vs incidental reactivation). In
      ventral/medial temporal lobe (VMTL) structures, incidental reactivation was as
      robust as target reactivation. In contrast, frontoparietal cortex exhibited
      stronger target than incidental reactivation; that is, goal-modulated
      reactivation. Reactivation was also associated with later memory. Frontoparietal
      biases toward target reactivation predicted subsequent memory for target
      features, whereas incidental reactivation in VMTL predicted subsequent memory for
      nontested features. These findings reveal a striking dissociation between goal
      modulated reactivation in frontoparietal cortex and incidental reactivation in
      VMTL. 

PMID- 24107945
TI  - Spatial representation and cognitive modulation of response variability in the
      lateral intraparietal area priority map.
AB  - The lateral intraparietal area (LIP) in the macaque contains a priority-based
      representation of the visual scene. We previously showed that the mean spike rate
      of LIP neurons is strongly influenced by spatially wide-ranging surround
      suppression in a manner that effectively sharpens the priority map. Reducing
      response variability can also improve the precision of LIP's priority map. We
      show that when a monkey plans a visually guided delayed saccade with an
      intervening distractor, variability (measured by the Fano factor) decreases both
      for neurons representing the saccade goal and for neurons representing the broad
      spatial surround. The reduction in Fano factor is maximal for neurons
      representing the saccade goal and steadily decreases for neurons representing
      more distant locations. LIP Fano factor changes are behaviorally significant:
      increasing expected reward leads to lower variability for the LIP representation
      of both the target and distractor locations, and trials with shorter latency
      saccades are associated with lower Fano factors in neurons representing the
      surround. Thus, the LIP Fano factor reflects both stimulus and behavioral
      engagement. Quantitative modeling shows that the interaction between mean spike
      count and target-receptive field (RF) distance in the surround during the
      predistractor epoch is multiplicative: the Fano factor increases more steeply
      with mean spike count further away from the RF. A negative-binomial model for LIP
      spike counts captures these findings quantitatively, suggests underlying
      mechanisms based on trial-by-trial variations in mean spike rate or burst-firing
      patterns, and potentially provides a principled framework to account
      simultaneously for the previously observed unsystematic relationships between
      spike rate and variability in different brain areas. 

PMID- 24107946
TI  - Myosin II regulates activity dependent compensatory endocytosis at central
      synapses.
AB  - Recent evidence suggests that endocytosis, not exocytosis, can be rate limiting
      for neurotransmitter release at excitatory CNS synapses during sustained activity
      and therefore may be a principal determinant of synaptic fatigue. At low
      stimulation frequencies, the probability of synaptic release is linked to the
      probability of synaptic retrieval such that evoked release results in
      proportional retrieval even for release of single synaptic vesicles. The exact
      mechanism by which the retrieval rates are coupled to release rates, known as
      compensatory endocytosis, remains unknown. Here we show that inactivation of
      presynaptic myosin II (MII) decreases the probability of synaptic retrieval. To
      be able to differentiate between the presynaptic and postsynaptic functions of
      MII, we developed a live cell substrate patterning technique to create defined
      neural circuits composed of small numbers of embryonic mouse hippocampal neurons
      and physically isolated from the surrounding culture. Acute application of
      blebbistatin to inactivate MII in circuits strongly inhibited evoked release but
      not spontaneous release. In circuits incorporating both control and MIIB knock
      out cells, loss of presynaptic MIIB function correlated with a large decrease in
      the amplitude of evoked release. Using activity-dependent markers FM1-43 and
      horseradish peroxidase, we found that MII inactivation greatly slowed vesicular
      replenishment of the recycling pool but did not impede synaptic release. These
      results indicate that MII-driven tension or actin dynamics regulate the major
      pathway for synaptic vesicle retrieval. Changes in retrieval rates determine the
      size of the recycling pool. The resulting effect on release rates, in turn,
      brings about changes in synaptic strength. 

PMID- 24107947
TI  - Ectopic expression of activated notch or SOX2 reveals similar and unique roles in
      the development of the sensory cell progenitors in the mammalian inner ear.
AB  - Hearing impairment or vestibular dysfunction in humans often results from a
      permanent loss of critical cell types in the sensory regions of the inner ear,
      including hair cells, supporting cells, or cochleovestibular neurons. These
      important cell types arise from a common sensory or neurosensory progenitor,
      although little is known about how these progenitors are specified. Studies have
      shown that Notch signaling and the transcription factor Sox2 are required for the
      development of these lineages. Previously we and others demonstrated that ectopic
      activation of Notch can direct nonsensory cells to adopt a sensory fate,
      indicating a role for Notch in early specification events. Here, we explore the
      relationship between Notch and SOX2 by ectopically activating these factors in
      nonsensory regions of the mouse cochlea, and demonstrate that, similar to Notch,
      SOX2 can specify sensory progenitors, consistent with a role downstream of Notch
      signaling. However, we also show that Notch has a unique role in promoting the
      proliferation of the sensory progenitors. We further demonstrate that Notch can
      only induce ectopic sensory regions within a certain time window of development,
      and that the ectopic hair cells display specialized stereocilia bundles similar
      to endogenous hair cells. These results demonstrate that Notch and SOX2 can both
      drive the sensory program in nonsensory cells, indicating these factors may be
      useful in cell replacement strategies in the inner ear. 

PMID- 24107948
TI  - Ovarian hormone loss impairs excitatory synaptic transmission at hippocampal CA3
      CA1 synapses.
AB  - Premature and long-term ovarian hormone loss following ovariectomy (OVX) is
      associated with cognitive impairment. This condition is prevented by estradiol
      (E2) therapy when initiated shortly following OVX but not after substantial
      delay. To determine whether these clinical findings are correlated with changes
      in synaptic functions, we used adult OVX rats to evaluate the consequences of
      short-term (7-10 d, OVXControl) and long-term (~5 months, OVXLT) ovarian hormone
      loss, as well as subsequent in vivo E2 treatment, on excitatory synaptic
      transmission at the hippocampal CA3-CA1 synapses important for learning and
      memory. The results show that ovarian hormone loss was associated with a marked
      decrease in synaptic strength. E2 treatment increased synaptic strength in
      OVXControl but not OVXLT rats, demonstrating a change in the efficacy for E2 5
      months following OVX. E2 also had a more rapid effect: within minutes of bath
      application, E2 acutely increased synaptic strength in all groups except OVXLT
      rats that did not receive in vivo E2 treatment. E2's acute effect was mediated
      postsynaptically, and required Ca(2+) influx through the voltage-gated Ca(2+)
      channels. Despite E2's acute effect, synaptic strength of OVXLT rats remained
      significantly lower than that of OVXControl rats. Thus, changes in CA3-CA1
      synaptic transmission associated with ovarian hormone loss cannot be fully
      reversed with delayed E2 treatment. Given that synaptic strength at CA3-CA1
      synapses is related to the ability to learn hippocampus-dependent tasks, these
      findings provide additional insights for understanding cognitive impairment
      associated long-term ovarian hormone loss and ineffectiveness for delayed E2
      treatment to maintain cognitive functions. 

PMID- 24107949
TI  - Interactions between white matter asymmetry and language during neurodevelopment.
AB  - The human brain is asymmetric in gross structure as well as functional
      organization. However, the developmental basis and trajectory of this asymmetry
      is unclear, and its relationship(s) to functional and cognitive development,
      especially language, remain to be fully elucidated. During infancy and early
      childhood, in concert with cortical gray matter growth, underlying axonal bundles
      become progressively myelinated. This myelination is critical for efficient and
      coherent interneuronal communication and, as revealed in animal studies, the
      degree of myelination changes in response to environment and neuronal activity.
      Using a novel quantitative magnetic resonance imaging method to investigate
      myelin content in vivo in human infants and young children, we investigated gross
      asymmetry of myelin in a large cohort of 108 typically developing children
      between 1 and 6 years of age, hypothesizing that asymmetry would predict language
      abilities in this cohort. While asymmetry of myelin content was evident in
      multiple cortical and subcortical regions, language ability was predicted only by
      leftward asymmetry of caudate and frontal cortex myelin content and rightward
      asymmetry in the extreme capsule. Importantly, the influence of this asymmetry
      was found to change with age, suggesting an age-specific influence of structure
      and myelin on language function. The relationship between language ability and
      asymmetry of myelin stabilized at ~4 years, indicating anatomical evidence for a
      critical time during development before which environmental influence on
      cognition may be greatest. 

PMID- 24107950
TI  - Speed-dependent contribution of callosal pathways to ipsilateral movements.
AB  - Transcallosal inhibitory interactions between primary motor cortices are
      important to suppress unintended movements in a resting limb during voluntary
      activation of the contralateral limb. The functional contribution of
      transcallosal inhibition targeting the voluntary active limb remains unknown.
      Using transcranial magnetic stimulation, we examined transcallosal inhibition [by
      measuring interhemispheric inhibition (IHI) and the ipsilateral silent period
      (iSP)] in the preparatory and execution phases of isotonic slower self-paced and
      ballistic movements performed by the ipsilateral index finger into abduction and
      the elbow into flexion in intact humans. We demonstrate decreased IHI in the
      preparatory phase of self-paced and ballistic index finger and elbow movements
      compared to rest; the decrease in IHI was larger during ballistic than self-paced
      movements. In contrast, in the execution phase, IHI and the iSP increased during
      ballistic compared to self-paced movements. Transcallosal inhibition was
      negatively correlated with reaction times in the preparatory phase and positively
      correlated with movement amplitude in the execution phase. Together, our results
      demonstrate a widespread contribution of transcallosal inhibition to ipsilateral
      movements of different speeds with a functional role during rapid movements; at
      faster speeds, decreased transcallosal inhibition in the preparatory phase may
      contribute to start movements rapidly, while the increase in the execution phase
      may contribute to stop the movement. We argue that transcallosal pathways enable
      signaling of the time of discrete behavioral events during ipsilateral movements,
      which is amplified by the speed of a movement. 

PMID- 24107951
TI  - Calcineurin interacts with the serotonin transporter C-terminus to modulate its
      plasma membrane expression and serotonin uptake.
AB  - Homeostasis of serotonergic transmission critically depends on the rate of
      serotonin reuptake via its plasma membrane transporter (SERT). SERT activity is
      tightly regulated by multiple mechanisms, including physical association with
      intracellular proteins and post-translational modifications, such as
      phosphorylation, but these mechanisms remain partially understood. Here, we show
      that SERT C-terminal domain recruits both the catalytic and regulatory subunits
      of the Ca(2+)-activated protein phosphatase calcineurin (CaN) and that the
      physical association of SERT with CaN is promoted by CaN activity. Coexpression
      of constitutively active CaN with SERT increases SERT cell surface expression and
      5-HT uptake in HEK-293 cells. It also prevents the reduction of 5-HT uptake
      induced by an acute treatment of cells with the protein kinase C activator beta
      PMA and concomitantly decreases PMA-elicited SERT phosphorylation. In addition,
      constitutive activation of CaN in vivo favors 5-HT uptake in the adult mouse
      brain, whereas CaN inhibition reduces cerebral 5-HT uptake. Constitutive
      activation of CaN also decreases immobility in the forced swim test, indicative
      of an antidepressant-like effect of CaN. These results identify CaN as an
      important regulator of SERT activity in the adult brain and provide a novel
      molecular substrate of clinical interest for the understanding of increased risk
      of mood disorders in transplanted patients treated with immunosuppressive CaN
      inhibitors. 

PMID- 24107952
TI  - Neural evidence for individual and cultural variability in the social comparison
      effect.
AB  - Although several studies have investigated the neural mechanism of social
      comparison, it remains unclear whether and how cultural membership, particularly
      independent versus interdependent cultures, may differentially shape the neural
      processes underlying social comparison. In the present functional magnetic
      resonance imaging (fMRI) study, we examined the behaviors and neural response
      patterns of Korean (i.e., interdependent culture) and American (i.e., independent
      culture) participants while performing a financial gambling task simultaneously
      and independently with a partner. Upon seeing the partner's income, greater
      modulation of the activity in the ventral striatum (VS) and the ventromedial
      prefrontal cortex (vmPFC) by relative gain was observed in Korean than American
      participants, suggesting greater sensitivity of Koreans toward social comparison.
      The strength of functional connectivity between the VS and the vmPFC predicted
      individual variability in the degree to which participants' decisions were
      affected by relative incomes. Additional model-based fMRI analysis further
      confirmed the primary role of the vmPFC in biasing decisions based on relative
      incomes. In summary, the present study provides the first neural evidence for
      decision biases due to social comparison and their individual and cultural
      variations. 

PMID- 24107954
TI  - On the dissociation between microsaccade rate and direction after peripheral
      cues: microsaccadic inhibition revisited.
AB  - Microsaccades during fixation exhibit distinct time courses of frequency and
      direction modulations after stimulus onsets, but the mechanisms for these
      modulations are unresolved. On the one hand, microsaccade rate drops within <100
      ms after stimulus onset, a phenomenon described as microsaccadic inhibition. On
      the other, the directions of the rare microsaccades that do occur during
      inhibition are, surprisingly, the most highly correlated with stimulus location.
      Here we show, using a combined computational and experimental approach, that
      these apparently dichotomous observations can simply result from a single
      mechanism: the phase resetting by stimulus onsets of ongoing microsaccadic
      oscillatory rhythms during fixation. Using experiments on monkeys and model
      simulations, we show that stimulus onsets act as countermanding stimuli, such as
      those in large saccadic countermanding tasks: they cancel an upcoming movement
      program and start a competing one, thus implementing phase resetting. We also
      show that the rare microsaccades occurring during microsaccadic inhibition are
      simply noncanceled movements in the countermanding framework and that they
      reflect the instantaneous state of visual representations expected in spatial
      maps representing stimuli. Remarkably, a dynamic interaction between the efficacy
      of the countermanding process and the metrics of the microsaccade being
      countermanded not only explains microsaccade rate changes, but it also predicts
      the time course patterns of microsaccade directions and amplitudes. Our
      parsimonious framework for understanding microsaccadic modulations around
      stimulus onsets allows analyzing microsaccades (and larger saccades) using the
      extensive toolkit of oscillatory dynamical systems often used for modeling
      spiking neurons, and it constrains neural models of microsaccade triggering. 

PMID- 24107953
TI  - The fine-scale functional correlation of striate cortex in sighted and blind
      people.
AB  - To what extent are spontaneous neural signals within striate cortex organized by
      vision? We examined the fine-scale pattern of striate cortex correlations within
      and between hemispheres in rest-state BOLD fMRI data from sighted and blind
      people. In the sighted, we find that corticocortico correlation is well modeled
      as a Gaussian point-spread function across millimeters of striate cortical
      surface, rather than degrees of visual angle. Blindness produces a subtle change
      in the pattern of fine-scale striate correlations between hemispheres. Across
      participants blind before the age of 18, the degree of pattern alteration
      covaries with the strength of long-range correlation between left striate cortex
      and Broca's area. This suggests that early blindness exchanges local, vision
      driven pattern synchrony of the striate cortices for long-range functional
      correlations potentially related to cross-modal representation. 

PMID- 24107955
TI  - A critical role for macrophages near axotomized neuronal cell bodies in
      stimulating nerve regeneration.
AB  - Macrophages have been implicated in peripheral nerve regeneration for some time,
      supposedly through their involvement in Wallerian degeneration, the process by
      which the distal nerve degenerates after axotomy and is cleared by phagocytosis.
      Thus, in several studies in which macrophage accumulation in the distal nerve was
      reduced and Wallerian degeneration inhibited, regeneration was delayed. However,
      this interpretation ignores the more recent findings that macrophages also
      accumulate around axotomized cell bodies. The function of macrophage action at
      this second site has not been clear. In two mutant strains of mice, the slow
      Wallerian degeneration (Wld(s)) mouse and the chemokine receptor CCR2 knock-out
      mouse, we report that macrophage accumulation after axotomy was abolished in both
      the dorsal root ganglion (DRG) and the distal sciatic nerve. To measure neurite
      outgrowth, DRG neurons were given a conditioning lesion, and outgrowth was
      measured in vitro 7 d later in the absence of the distal nerve segment. The
      increased growth normally seen after a conditioning lesion did not occur or was
      reduced in Wld(s) or CCR2(-/-) mice. In the superior cervical ganglion (SCG),
      particularly in Wld(s) mice, macrophage accumulation was reduced but not
      abolished after axotomy. In SCG neurons from Wld(s) mice, the conditioning lesion
      response was unchanged; however, in CCR2(-/-) mice in which the effect on
      macrophage accumulation was greater, SCG neurite outgrowth was significantly
      reduced. These results indicate that macrophages affect neurite outgrowth by
      acting at the level of peripheral ganglia in addition to any effects they might
      produce by facilitation of Wallerian degeneration. 

PMID- 24107957
TI  - Real-time imaging of amygdalar network dynamics in vitro reveals a
      neurophysiological link to behavior in a mouse model of extremes in trait
      anxiety.
AB  - In humans and numerous other mammalian species, individuals considerably vary in
      their level of trait anxiety. This well known phenomenon is closely related to
      the etiology of several psychiatric disorders, but its neurophysiological basis
      remains poorly understood. Here, we applied voltage-sensitive dye imaging to
      brain slices from animals of the high (HAB), normal (NAB), and low (LAB) trait
      anxiety mouse model and investigated whether evoked neuronal activity
      propagations from the lateral (LA) to the central (CeA) amygdala differ in their
      relative strength among HAB, NAB, and LAB mice. For this purpose, we divided a
      real-time measure of neuronal population activity in the CeA by a respective
      measure obtained for the LA. This calculation yielded the metric "CeA/LA
      activity." Our data clearly demonstrate a positive correlation between trait
      anxiety levels evaluated by the elevated plus-maze test and CeA/LA activity.
      Moreover, we found reduced CeA/LA activity in HAB mice, which responded with
      decreased anxiety levels to an environmental enrichment and, inversely, detected
      increased anxiety levels and CeA/LA activity in LAB mice that experienced chronic
      mild stress. We did not observe differences in the spread of neuronal activity in
      the motor and visual cortex among HAB, NAB, and LAB animals. Collectively, these
      findings provide evidence that, in mammals, interindividual variability in trait
      anxiety is causally linked to individual variations in the physiological
      constitution of the LA-to-CeA circuitry that give rise to a differential
      regulation of neuronal signal flow through this fundamental input-output network
      of the amygdala. 

PMID- 24107956
TI  - Functional maturation of the executive system during adolescence.
AB  - Adolescence is characterized by rapid development of executive function. Working
      memory (WM) is a key element of executive function, but it is not known what
      brain changes during adolescence allow improved WM performance. Using a fractal n
      back fMRI paradigm, we investigated brain responses to WM load in 951 human
      youths aged 8-22 years. Compared with more limited associations with age, WM
      performance was robustly associated with both executive network activation and
      deactivation of the default mode network. Multivariate patterns of brain
      activation predicted task performance with a high degree of accuracy, and also
      mediated the observed age-related improvements in WM performance. These results
      delineate a process of functional maturation of the executive system, and suggest
      that this process allows for the improvement of cognitive capability seen during
      adolescence. 

PMID- 24107958
TI  - Rapid functional reorganization in human cortex following neural perturbation.
AB  - Despite the human brain's ability to rapidly reorganize neuronal activity
      patterns in response to interactions with the environment (e.g., learning), it
      remains unclear whether compensatory mechanisms occur, on a similar time scale,
      in response to exogenous cortical perturbations. To investigate this, we
      disrupted normal neural function via repetitive transcranial magnetic stimulation
      and assessed, using fMRI, activity changes associated with performance on a
      working memory task. Although transcranial magnetic stimulation disrupted neural
      activity in task-related brain regions, performance was not affected. Critically,
      another brain region not previously engaged by the task was recruited to uphold
      memory performance. Thus, functional reorganization of cortical activity can
      occur within minutes of neural disruption to maintain cognitive abilities. 

PMID- 24107959
TI  - Prior expectations bias sensory representations in visual cortex.
AB  - Perception is strongly influenced by expectations. Accordingly, perception has
      sometimes been cast as a process of inference, whereby sensory inputs are
      combined with prior knowledge. However, despite a wealth of behavioral literature
      supporting an account of perception as probabilistic inference, the neural
      mechanisms underlying this process remain largely unknown. One important question
      is whether top-down expectation biases stimulus representations in early sensory
      cortex, i.e., whether the integration of prior knowledge and bottom-up inputs is
      already observable at the earliest levels of sensory processing. Alternatively,
      early sensory processing may be unaffected by top-down expectations, and
      integration of prior knowledge and bottom-up input may take place in downstream
      association areas that are proposed to be involved in perceptual decision-making.
      Here, we implicitly manipulated human subjects' prior expectations about visual
      motion stimuli, and probed the effects on both perception and sensory
      representations in visual cortex. To this end, we measured neural activity
      noninvasively using functional magnetic resonance imaging, and applied a forward
      modeling approach to reconstruct the motion direction of the perceived stimuli
      from the signal in visual cortex. Our results show that top-down expectations
      bias representations in visual cortex, demonstrating that the integration of
      prior information and sensory input is reflected at the earliest stages of
      sensory processing. 

PMID- 24107960
TI  - Anatomical evidence that the superior colliculus controls saccades through
      central mesencephalic reticular formation gating of omnipause neuron activity.
AB  - Omnipause neurons (OPNs) within the nucleus raphe interpositus (RIP) help gate
      the transition between fixation and saccadic eye movements by monosynaptically
      suppressing activity in premotor burst neurons during fixation, and releasing
      them during saccades. Premotor neuron activity is initiated by excitatory input
      from the superior colliculus (SC), but how the tectum's saccade-related activity
      turns off OPNs is not known. Since the central mesencephalic reticular formation
      (cMRF) is a major SC target, we explored whether this nucleus has the appropriate
      connections to support tectal gating of OPN activity. In dual-tracer experiments
      undertaken in macaque monkeys (Macaca fascicularis), cMRF neurons labeled
      retrogradely from injections into RIP had numerous anterogradely labeled
      terminals closely associated with them following SC injections. This suggested
      the presence of an SC-cMRF-RIP pathway. Furthermore, anterograde tracers injected
      into the cMRF of other macaques labeled axonal terminals in RIP, confirming this
      cMRF projection. To determine whether the cMRF projections gate OPN activity,
      postembedding electron microscopic immunochemistry was performed on anterogradely
      labeled cMRF terminals with antibody to GABA or glycine. Of the terminals
      analyzed, 51.4% were GABA positive, 35.5% were GABA negative, and most contacted
      glycinergic cells. In summary, a trans-cMRF pathway connecting the SC to the RIP
      is present. This pathway contains inhibitory elements that could help gate
      omnipause activity and allow other tectal drives to induce the bursts of firing
      in premotor neurons that are necessary for saccades. The non-GABAergic cMRF
      terminals may derive from fixation units in the cMRF. 

PMID- 24107961
TI  - Visualization of synaptic inhibition with an optogenetic sensor developed by cell
      free protein engineering automation.
AB  - We describe an engineered fluorescent optogenetic sensor, SuperClomeleon, that
      robustly detects inhibitory synaptic activity in single, cultured mouse neurons
      by reporting intracellular chloride changes produced by exogenous GABA or
      inhibitory synaptic activity. Using a cell-free protein engineering automation
      methodology that bypasses gene cloning, we iteratively constructed, produced, and
      assayed hundreds of mutations in binding-site residues to identify improvements
      in Clomeleon, a first-generation, suboptimal sensor. Structural analysis revealed
      that these improvements involve halide contacts and distant side chain
      rearrangements. The development of optogenetic sensors that respond to neural
      activity enables cellular tracking of neural activity using optical, rather than
      electrophysiological, signals. Construction of such sensors using in vitro
      protein engineering establishes a powerful approach for developing new probes for
      brain imaging. 

PMID- 24107962
TI  - Shaker-related potassium channels in the central medial nucleus of the thalamus
      are important molecular targets for arousal suppression by volatile general
      anesthetics.
AB  - The molecular targets and neural circuits that underlie general anesthesia are
      not fully elucidated. Here, we directly demonstrate that Kv1-family (Shaker
      related) delayed rectifier K(+) channels in the central medial thalamic nucleus
      (CMT) are important targets for volatile anesthetics. The modulation of Kv1
      channels by volatiles is network specific as microinfusion of ShK, a potent
      inhibitor of Kv1.1, Kv1.3, and Kv1.6 channels, into the CMT awakened sevoflurane
      anesthetized rodents. In heterologous expression systems, sevoflurane,
      isoflurane, and desflurane at subsurgical concentrations potentiated delayed
      rectifier Kv1 channels at low depolarizing potentials. In mouse thalamic brain
      slices, sevoflurane inhibited firing frequency and delayed the onset of action
      potentials in CMT neurons, and ShK-186, a Kv1.3-selective inhibitor, prevented
      these effects. Our findings demonstrate the exquisite sensitivity of delayed
      rectifier Kv1 channels to modulation by volatile anesthetics and highlight an
      arousal suppressing role of Kv1 channels in CMT neurons during the process of
      anesthesia. 

PMID- 24107963
TI  - Activation of extrasynaptic NMDARs at individual parallel fiber-molecular layer
      interneuron synapses in cerebellum.
AB  - NMDA receptors (NMDARs) expressed by cerebellar molecular layer interneurons
      (MLIs) are not activated by single exocytotic events but can respond to glutamate
      spillover following coactivation of adjacent parallel fibers (PFs), indicating
      that NMDARs are perisynaptic. Several types of synaptic plasticity rely on these
      receptors but whether they are activated at isolated synapses is not known. Using
      a combination of electrophysiological and optical recording techniques in acute
      slices of rat cerebellum, along with modeling, we find that repetitive activation
      of single PF-MLI synapses can activate NMDARs in MLIs. High-frequency
      stimulation, multivesicular release (MVR), or asynchronous release can each
      activate NMDARs. Frequency facilitation was found at all PF-MLI synapses but,
      while some showed robust MVR with increased release probability, most were
      limited to univesicular release. Together, these results reveal a functional
      diversity of PF synapses, which use different mechanisms to activate NMDARs. 

PMID- 24107964
TI  - Neonatal E. coli infection causes neuro-behavioral deficits associated with
      hypomyelination and neuronal sequestration of iron.
AB  - Recent evidence indicates that inflammatory insults in neonates significantly
      influenced white matter development and caused behavioral deficits that manifest
      in young adulthood. The mechanisms underlying these developmental and behavioral
      complications, however, are not well understood. We hypothesize that acute brain
      inflammation caused by neonatal infection reduces the bioavailability of iron
      required for oligodendrocyte maturation and white matter development. Here, we
      confirm that peripheral Escherichia coli infection in neonates at postnatal day 3
      (P3) caused acute brain inflammation that was resolved within 72 h. Nonetheless,
      transient early life infection (ELI) profoundly influenced behavior, white matter
      development, and iron homeostasis in the brain. For instance, mice exposed to E.
      coli as neonates had increased locomotor activity and impaired motor coordination
      as juveniles (P35) and young adults (P60). In addition, these behavioral deficits
      were associated with marked hypomyelination and a reduction of oligodendrocytes
      in subcortical white matter and motor cortex. Moreover, ELI altered transcripts
      related to cellular sequestration of iron in the brain including hepcidin,
      ferroportin, and L-ferritin. For example, ELI increased hepcidin mRNA and
      decreased ferroportin mRNA and protein in the brain at P4, which preceded
      increased L-ferritin mRNA at P12. Consistent with the mRNA results, L-ferritin
      protein was robustly increased at P12 specifically in neurons of E. coli infected
      mice. We interpret these data to indicate that neonatal infection causes
      significant neuronal sequestration of iron at a time point before myelination.
      Together, these data indicate a possible role for aberrant neuronal iron storage
      in neonatal infection-induced disturbances in myelination and behavior. 

PMID- 24107966
TI  - Representation of spatial- and object-specific behavioral goals in the dorsal
      globus pallidus of monkeys during reaching movement.
AB  - The dorsal aspect of the globus pallidus (GP) communicates with the prefrontal
      cortex and higher-order motor areas, indicating that it plays a role in goal
      directed behavior. We examined the involvement of dorsal GP neurons in behavioral
      goal monitoring and maintenance, essential components of executive function. We
      trained two macaque monkeys to choose a reach target based on relative target
      position in a spatial goal task or a target shape in an object-goal task. The
      monkeys were trained to continue to choose a certain behavioral goal when reward
      volume was constant and to switch the goals when the volume began to decrease.
      Because the judgment for the next goal was made in the absence of visual signals,
      the monkeys were required to monitor and maintain the chosen goals during the
      reaching movement. We obtained three major findings. (1) GP neurons reflected
      more of the relative spatial position than the shape of the reaching target
      during the spatial goal task. During the object-goal task, the shape of the
      reaching object was represented more than the relative position. (2) The
      selectivity of individual neurons for the relative position was enhanced during
      the spatial goal task, whereas the object-shape selectivity was enhanced during
      the object-goal task. (3) When the monkeys switched the goals, the selectivity
      for either the position or shape also switched. Together, these findings suggest
      that the dorsal GP is involved in behavioral goal monitoring and maintenance
      during execution of goal-oriented actions, presumably in collaboration with the
      prefrontal cortex. 

PMID- 24107967
TI  - GDNF signaling levels control migration and neuronal differentiation of enteric
      ganglion precursors.
AB  - Pleiotropic growth factors play a number of critical roles in continuous
      processes of embryonic development; however, the mechanisms by which a single
      regulatory factor is able to orchestrate diverse developmental events remain
      imperfectly understood. In the development of the enteric nervous system (ENS),
      myenteric ganglia (MGs) form initially, after which the submucosal ganglia (SMGs)
      develop by radial inward migration of immature ENS precursors from the myenteric
      layer. Here, we demonstrate that glial cell line-derived neurotrophic factor
      (GDNF) is essential for the formation not only of the MGs, but the SMGs as well,
      establishing GDNF as a long-term acting neurotrophic factor for ENS development
      in a mouse model. GDNF promotes radial migration of SMG precursors.
      Interestingly, premigratory SMG precursors in the myenteric layer were
      distinguished from the surrounding neuronally differentiating cells by their
      lower activation of the GDNF-mediated MAPK pathway, suggesting that low
      activation of GDNF downstream pathways is required for the maintenance of the
      immature state. ENS precursors devoid of GDNF signaling during midgestation halt
      their migration, survive, and remain in an undifferentiated state over the long
      term in vivo. Reactivation of GDNF signaling in these dormant precursors restores
      their migration and neuronal differentiation in gut organ culture. These findings
      suggest that pleiotropic function of GDNF is at least in part governed by
      modulating levels of intracellular activation of GDNF downstream pathways; high
      activation triggers neuronal differentiation, whereas low activation is crucial
      for the maintenance of progenitor state. 

PMID- 24107965
TI  - Klotho regulates retinal pigment epithelial functions and protects against
      oxidative stress.
AB  - The retinal pigment epithelium (RPE) is a highly specialized CNS tissue that
      plays crucial roles in retinal homeostasis. Age-related morphological changes in
      the RPE have been associated with retinal degenerative disorders; our
      understanding of the underlying molecular mechanisms, however, remains
      incomplete. Here we report on a key role of Klotho (Kl), an aging-suppressor
      gene, in retinal health and RPE physiology. Kl(-/-) mice show RPE and
      photoreceptor degeneration, reduced pigment synthesis in the RPE, and impaired
      phagocytosis of the outer segment of the photoreceptors. Klotho protein (KL) is
      expressed in primary cultured human RPE, and regulates pigment synthesis by
      increasing the expression of MITF (microphthalmia transcription factor) and TYR
      (tyrosinase), two pivotal genes in melanogenesis. Importantly, KL increases
      phagocytosis in cultured RPE by inducing gene expression of MERTK/AXL/TYRO3.
      These effects of KL are mediated through cAMP-PKA-dependent phosphorylation of
      transcription factor CREB. In cultured human RPE, KL increases the l-3,4
      dihydroxyphenylalanine synthesis and inhibits vascular endothelial growth factor
      (VEGF) secretion from basal membrane by inhibiting IGF-1 signaling and VEGF
      receptor 2 phosphorylation. KL also regulates the expression of stress-related
      genes in RPE, lowers the production of reactive oxygen species, and thereby,
      protects RPE from oxidative stress. Together, our results demonstrate a critical
      function for KL in mouse retinal health in vivo, and a protective role toward
      human RPE cells in vitro. We conclude that KL is an important regulator of RPE
      homeostasis, and propose that an age-dependent decline of KL expression may
      contribute to RPE degeneration and retinal pathology. 

PMID- 24107968
TI  - Parceling human accumbens into putative core and shell dissociates encoding of
      values for reward and pain.
AB  - In addition to their well-established role in signaling rewarding outcomes and
      reward-predictive cues and in mediating positive reinforcement, there is growing
      evidence that nucleus accumbens (NAc) neurons also signal aversive events and
      cues that predict them. Here we use diffusion tractography to subdivide the right
      NAc into lateral-rostral (putative core, pcore) and medial-caudal (putative
      shell, pshell) subdivisions in humans. The two subregions exhibited differential
      structural connectivity, based on probabilistic tractography, to prefrontal
      cortical and subcortical limbic regions. We also demonstrate unique roles for
      each of the two subdivisions for monetary reward and thermal pain perception
      tasks: pshell signaling impending pain and value predictions for monetary gambles
      and pcore activating with anticipation of cessation of thermal pain (signaling
      reward value of analgesia). We examined functional connectivity for resting
      state, monetary reward, and thermal pain tasks, and for all three conditions
      observed that pcore and pshell of right NAc exhibit distinct patterns of
      synchrony (functional connectivity) to prefrontal cortical and subcortical limbic
      targets within the right hemisphere. To validate the NAc segregation, we mirrored
      the coordinates of right NAc pcore and pshell onto the left hemisphere and
      examined structural and resting state connectivity in the left hemisphere. This
      latter analysis closely replicated target-specific connections we obtained for
      the right hemisphere. Overall, we demonstrate that the human NAc can be parceled
      based on structural and functional connectivity, and that activity in these
      subdivisions differentially encodes values for expected pain relief and for
      expected monetary reward. 

PMID- 24107970
TI  - Multivariable Static Ankle Mechanical Impedance With Active Muscles.
AB  - This paper reports quantification of multivariable static ankle mechanical
      impedance when muscles were active. Repetitive measurements using a highly
      backdrivable therapeutic robot combined with robust function approximation
      methods enabled reliable characterization of the nonlinear torque-angle relation
      at the ankle in two coupled degrees of freedom simultaneously, a combination of
      dorsiflexion-plantarflexion and inversion-eversion, and how it varied with muscle
      activation. Measurements on 10 young healthy seated subjects quantified the
      behavior of the human ankle when muscles were active at 10% of maximum voluntary
      contraction. Stiffness, a linear approximation to static ankle mechanical
      impedance, was estimated from the continuous vector field. As with previous
      measurements when muscles were maximally relaxed, we found that ankle stiffness
      was highly direction-dependent, being weakest in inversion/eversion.
      Predominantly activating a single muscle or co-contracting antagonistic muscles
      significantly increased ankle stiffness in all directions but it increased more
      in the sagittal plane than in the frontal plane, accentuating the relative
      weakness of the ankle in the inversion-eversion direction. Remarkably, the
      observed increase was not consistent with simple superposition of muscle
      generated stiffness, which may be due to the contribution of unmonitored deep
      ankle muscles. Implications for the assessment of neuro-mechanical disorders are
      discussed. 

PMID- 24107969
TI  - Perceptual modulation of motor--but not visual--responses in the frontal eye
      field during an urgent-decision task.
AB  - Neuronal activity in the frontal eye field (FEF) ranges from purely motor
      (related to saccade production) to purely visual (related to stimulus presence).
      According to numerous studies, visual responses correlate strongly with early
      perceptual analysis of the visual scene, including the deployment of spatial
      attention, whereas motor responses do not. Thus, functionally, the consensus is
      that visually responsive FEF neurons select a target among visible objects,
      whereas motor-related neurons plan specific eye movements based on such earlier
      target selection. However, these conclusions are based on behavioral tasks that
      themselves promote a serial arrangement of perceptual analysis followed by motor
      planning. So, is the presumed functional hierarchy in FEF an intrinsic property
      of its circuitry or does it reflect just one possible mode of operation? We
      investigate this in monkeys performing a rapid-choice task in which, crucially,
      motor planning always starts ahead of task-critical perceptual analysis, and the
      two relevant spatial locations are equally informative and equally likely to be
      target or distracter. We find that the choice is instantiated in FEF as a
      competition between oculomotor plans, in agreement with model predictions.
      Notably, although perception strongly influences the motor neurons, it has little
      if any measurable impact on the visual cells; more generally, the more dominant
      the visual response, the weaker the perceptual modulation. The results indicate
      that, contrary to expectations, during rapid saccadic choices perceptual
      information may directly modulate ongoing saccadic plans, and this process is not
      contingent on prior selection of the saccadic goal by visually driven FEF
      responses. 

PMID- 24107971
TI  - Host effects on the optically active 4f and 5d levels of Ce3+ in garnets.
AB  - When Ce(3+) is doped in a garnet, it substitutes for some cations. The effect of
      the substitution on the optically active 4f and 5d levels of Ce(3+) can be
      analyzed in terms of an undistorted substitution followed by a structural
      relaxation, but, whereas the contribution of the undistorted substitution can be
      predicted/calculated using the crystallographic structure of the pure garnet,
      which is at hand, that of the structural relaxation demands the detailed local
      structure around the Ce(3+) impurity, which is hard to know. Hence the importance
      of knowing the role of the undistorted substitution. What we study in this paper
      is the role of the unrelaxed host effects on the 4f and 5d levels of Ce(3+)-doped
      garnets (i.e. the interactions between Ce and the second and more distant
      neighbors). When they are added to the (previously studied) unrelaxed first
      neighbor effects, they give the contributions of the undistorted substitutions.
      We performed spin-orbit coupling, relativistic, embedded cluster, wave function
      based ab initio calculations on the (CeO8)(13-) cluster under the effects of the
      embedding potentials of 21 selected garnets of Si, Al, and Ga, which have been
      obtained in this work, using experimental unrelaxed structures of the pure
      garnets. The calculations reveal that the unrelaxed host effect: (1) produces a
      red shift of the first 4f -> 5d transition and (2) is an important contribution
      to this transition which plays a very important role in differentiating the
      values it has in different garnet families. The unrelaxed host effect is found to
      be responsible for the low value of the first 4f -> 5d transition in Ce(3+)-doped
      Lu2CaMg2Si3O12. It is analyzed in terms of 5d and 4f centroid energy
      contributions and crystal field splitting contributions in the 21 doped garnets.
      The effect on the splittings of the 4f and 5d levels is also discussed. The
      undistorted host approximation is found to give reasonable comparison with
      experiments, so that it represents a relatively fast way to provide reliable ab
      initio information on the 4f and 5d levels of Ce(3+) in garnets. 

PMID- 24107972
TI  - Hope, quality of life, and benefit from treatment in women having chemotherapy
      for platinum-resistant/refractory recurrent ovarian cancer: the gynecologic
      cancer intergroup symptom benefit study.
AB  - Chemotherapy for platinum-resistant/refractory ovarian cancer is motivated by the
      hope of benefit. We sought to determine the relationships between: (a) trait
      hope, expectation of symptom benefit from chemotherapy, and anxiety and
      depression; (b) hope and perceived efficacy of chemotherapy; and (c) unfulfilled
      hope (where expectations for benefit are not fulfilled) and depression. Methods.
      Adult patients enrolled within stage 1 of the Gynecologic Cancer Intergroup
      Symptom Benefit Study were included. Patient. Reported outcomes were collected
      from 126 women with predominantly platinum-resistant ovarian cancer at baseline,
      prior to the first four treatment cycles (12-16 weeks), and four weeks after
      completing chemotherapy or at disease progression, whichever came first.
      Associations were assessed with Spearman rank correlation coefficient (r) and
      odds ratio. Results. Trait hope and expectation of symptom benefit from
      chemotherapy were weakly correlated with each other (r = 0.25). Trait hope, but
      not expectation of symptom benefit, was negatively correlated with anxiety (r = 
      0.43) and depression (r = -0.50). The smaller the discrepancy between perceived
      and expected symptom benefit, the less likely the patient was to have scores
      indicative of depression (odds ratio: 0.68; 95% confidence interval: 0.49-0.96; p
      = .026). Conclusion. Trait hope and expectation of symptom benefit from
      chemotherapy appear to be distinct and independent of the aspects of quality of
      life and scores for depression. Hope did not appear to affect perceived efficacy
      of chemotherapy in alleviating symptoms, but women whose expectation of symptom
      benefit from chemotherapy was not fulfilled were more likely to have scores
      indicative of depression. It may be preferable to encourage hope toward
      achievable goals rather than toward benefits from chemotherapy. 

PMID- 24107973
TI  - Treatment of dexamethasone-induced hiccup in chemotherapy patients by
      methylprednisolone rotation.
AB  - Dexamethasone-induced hiccup (DIH) is an underrecognized symptom in patients with
      cancer, and little information is available about its treatment. The aims of this
      study were to investigate the feasibility of methylprednisolone rotation as
      treatment and to confirm the male predominance among those with cancer who
      experienced DIH during chemotherapy. Methods. Persons with cancer who experienced
      hiccups during chemotherapy treatment and who were receiving treatment with
      dexamethasone were presumed to have DIH. The following algorithmic practice was
      implemented for antiemetic corticosteroid use: rotation from dexamethasone to
      methylprednisolone in the next cycle and dexamethasone re-administration in the
      second cycle of chemotherapy after recognition of hiccups to confirm DIH. All
      other antiemetics except corticosteroid remained unchanged. Patients (n = 40)
      were recruited from eight cancer centers in Korea from September 2012 to April
      2013. Data were collected retrospectively. Results. Hiccup intensity (numeric
      rating scale [NRS]: 5.38 vs. 0.53) and duration (68.44 minutes vs. 1.79 minutes)
      were significantly decreased after rotation to methylprednisolone, while
      intensity of emesis was not increased (NRS: 2.63 vs. 2.08). Median dose of
      dexamethasone and methylprednisolone were 10 mg and 50 mg, respectively. Thirty
      four (85%) of 40 patients showed complete resolution of hiccups after
      methylprednisolone rotation in the next cycle. Of these 34 patients, 25 (73.5%)
      had recurrence of hiccups after dexamethasone re-administration. Compared with
      baseline values, hiccup intensity (NRS: 5.24 vs. 2.44) and duration (66.43
      minutes vs. 22.00 minutes) were significantly attenuated after dexamethasone re
      administration. Of the 40 eligible patients, 38 (95%) were male. Conclusion. DIH
      during chemotherapy could be controlled without losing antiemetic potential by
      replacing dexamethasone with methylprednisolone. We also identified a male
      predominance of DIH. Further prospective studies are warranted. 

PMID- 24107974
TI  - Adsorption of carbon dioxide by MIL-101(Cr): regeneration conditions and
      influence of flue gas contaminants.
AB  - MIL-101(Cr) has drawn much attention due to its high stability compared with
      other metal-organic frameworks. In this study, three trace flue gas contaminants
      (H2O, NO, SO2) were each added to a 10 vol% CO2/N2 feed flow and found to have a
      minimal impact on the adsorption capacity of CO2. In dynamic CO2 regeneration
      experiments, complete regeneration occurred in 10 min at 328 K for temperature
      swing adsorption-N2-stripping under a 50 cm(3)/min N2 flow and at 348 K for
      vacuum-temperature swing adsorption at 20 KPa. Almost 99% of the pre-regeneration
      adsorption capacity was preserved after 5 cycles of adsorption/desorption under a
      gas flow of 10 vol% CO2, 100 ppm SO2, 100 ppm NO, and 10% RH, respectively.
      Strong resistance to flue gas contaminants, mild recovery conditions, and
      excellent recycling efficiency make MIL-101(Cr) an attractive adsorbent support
      for CO2 capture.

PMID- 24107975
TI  - Yolk-shell hybrid nanoparticles with magnetic and pH-sensitive properties for
      controlled anticancer drug delivery.
AB  - A facile and effective way for the preparation of nano-sized Fe3O4@graphene yolk
      shell nanoparticles via a hydrothermal method is developed. Moreover, the
      targeting properties of the materials for anticancer drug (doxorubicin
      hydrochloride) delivery are investigated. Excitingly, these hybrid materials
      possess favorable dispersibility, good superparamagnetism (the magnetic
      saturation value is 45.740 emu g(-1)), high saturated loading capacity (2.65 mg
      mg(-1)), and effective loading (88.3%). More importantly, the composites exhibit
      strong pH-triggered drug release response (at the pH value of 5.6 and 7.4, the
      release rate was 24.86% and 10.28%, respectively) and good biocompatibility over
      a broad concentration range of 0.25-100 MUg mL(-1) (the cell viability was 98.52%
      even at a high concentration of 100 MUg mL(-1)) which sheds light on their
      potentially bright future for bio-related applications. 

PMID- 24107976
TI  - Real-Time Stimulus Artifact Rejection Via Template Subtraction.
AB  - This paper presents an infinite impulse response (IIR) temporal filtering
      technique for real-time stimulus artifact rejection (SAR) based on template
      subtraction. A system architecture for the IIR SAR algorithm is developed, and
      the operation of the algorithm with fixed-point computation is analyzed to obtain
      the number of bits for the internal nodes of the system, considering dynamic
      range and fraction length requirements for optimum performance. Further, memory
      initialization with the first recorded stimulus artifact is proposed and shown to
      significantly decrease the IIR system response time, especially when artifacts
      are highly reproducible in consecutive stimulation cycles. The proposed system
      architecture is hardware-implemented on a field-programmable gate array (FPGA)
      and tested using two sets of prerecorded neural data from a rat and an Aplysia
      californica (a marine sea slug) obtained from two different laboratories. The
      measured results from the FPGA verify that the system can indeed remove the
      stimulus artifacts from the contaminated neural data in real time and recover the
      neural action potentials that occur on the tail end of the artifact (as close as
      within 0.5 ms after the artifact spike). The root-mean-square (rms) value of the
      pre-processed stimulus artifact is reduced on average by a factor of 17 (Aplysia
      californica) and 5.3 (rat) post-processing.

PMID- 24107977
TI  - Rapid detection of E. coli bacteria using potassium-sensitive FETs in CMOS.
AB  - A novel integrated system for the detection of live bacteria in less than 10
      minutes is presented. It utilizes the specificity of bacteriophages as biological
      detection elements with the sensitivity of integrated ion-selective field-effect
      transistors (ISFETs) implemented in conventional 0.18 MUm CMOS with additional
      post-processes PVC-based potassium-sensitive membrane to provide a rapid, low
      cost bacteria detection platform. Experimental methods to cancel ISFET non
      idealities as well as data processing techniques to enhance detection capability
      of the bacteria sensor are demonstrated. Three groups of experimental results are
      provided using four strains of E. coli with two bacteriophages at two different
      temperatures. Measurements incorporating positive and negative control
      experiments are presented that successfully exhibit sensor specificity as well
      detection capability. 

PMID- 24107978
TI  - Improved Signal Processing Methods for Velocity Selective Neural Recording Using
      Multi-Electrode Cuffs.
AB  - This paper describes an improved system for obtaining velocity spectral
      information from electroneurogram recordings using multi-electrode cuffs (MECs).
      The starting point for this study is some recently published work that considers
      the limitations of conventional linear signal processing methods ('delay-and
      add') with and without additive noise. By contrast to earlier linear methods, the
      present paper adopts a fundamentally non-linear velocity classification approach
      based on a type of artificial neural network (ANN). The new method provides a
      unified approach to the solution of the two main problems of the earlier delay
      and-add technique, i.e., a damaging decline in both velocity selectivity and
      velocity resolution at high velocities. The new method can operate in real-time,
      is shown to be robust in the presence of noise and also to be relatively
      insensitive to the form of the action potential waveforms being classified.

PMID- 24107979
TI  - Self-management approaches for osteoarthritis in the hand: a 2*2 factorial
      randomised trial.
AB  - BACKGROUND: Osteoarthritis is the leading cause of disability in older adults.
      Evidence of effectiveness for self-management of hand osteoarthritis is lacking.
      METHODS: In this randomised, factorial trial, we evaluated the effectiveness of
      joint protection versus no joint protection, and hand exercise versus no hand
      exercise in adults, 50 years of age or older, with hand osteoarthritis. Following
      a population survey (n=12 297), eligible individuals were randomly assigned
      (1:1:1:1) to: leaflet and advice; joint protection; hand exercise; joint
      protection plus hand exercise. Joint protection and hand exercises were delivered
      by nine occupational therapists, over four group sessions. The primary outcome
      was the OARSI/OMERACT responder criteria at 6 months. Outcomes were collected
      blind to allocation (3, 6, 12 m). Analysis was by intention to treat. RESULTS: Of
      257 participants randomised (65:62:65:65) (mean age (SD) 66 years (9.1); female
      66%) follow-up was 85% at 6 m (n=212). Baseline characteristics and loss to
      follow-up were similar between groups. There were no reported treatment side
      effects. At 6 m 33% assigned joint protection were responders compared with 21%
      with no joint protection (p=0.03). Of those assigned hand exercises, 28% were
      responders compared with 25% with no exercises (n.s.). Differences in secondary
      outcomes were not statistically significant, except for improvement in pain self
      efficacy with joint protection (3 m p=0.002; 6 m p=0.001; 12 m p=0.03).
      CONCLUSIONS: These findings show that occupational therapists can support self
      management in older adults with hand osteoarthritis, and that joint protection
      provides an effective intervention for medium term outcome. (Funded by the
      Arthritis Research UK ISRCTN 33870549).

PMID- 24107980
TI  - Response to Dr Bolland's eLetter: Strontium and cardiovascular events.

PMID- 24107981
TI  - Revisiting comorbidities in gout: a cluster analysis.
AB  - OBJECTIVES: The reciprocal links between comorbidities and gout are complex. We
      used cluster analysis to attempt to identify different phenotypes on the basis of
      comorbidities in a large cohort of patients with gout. METHODS: This was a cross
      sectional multicentre study of 2763 gout patients conducted from November 2010 to
      May 2011. Cluster analysis was conducted separately for variables and for
      observations in patients, measuring proximity between variables and identifying
      homogeneous subgroups of patients. Variables used in both analyses were
      hypertension, obesity, diabetes, dyslipidaemia, heart failure, coronary heart
      disease, renal failure, liver disorders and cancer. RESULTS: Comorbidities were
      common in this large cohort of patients with gout. Abdominal obesity,
      hypertension, metabolic syndrome and dyslipidaemia increased with gout duration,
      even after adjustment for age and sex. Five clusters (C1-C5) were found. Cluster
      C1 (n=332, 12%) consisted of patients with isolated gout and few comorbidities.
      In C2 (n=483, 17%), all patients were obese, with a high prevalence of
      hypertension. C3 (n=664, 24%) had the greatest proportion of patients with type 2
      diabetes (75%). In C4 (n=782, 28%), almost all patients presented with
      dyslipidaemia (98%). Finally, C5 (n=502, 18%) consisted of almost all patients
      with a history of cardiovascular disease and renal failure, with a high rate of
      patients receiving diuretics. CONCLUSIONS: Cluster analysis of comorbidities in
      gout allowed us to identify five different clinical phenotypes, which may reflect
      different pathophysiological processes in gout.

PMID- 24107983
TI  - Electrical stimulation-evoked dopamine release in the primate striatum.
AB  - BACKGROUND: Primate studies demonstrate that high-frequency electrical
      stimulation (HFS) of the caudate can enhance learning. Importantly, in these
      studies, stimulation was applied following the execution of behavior and the
      effect persisted into subsequent trials, suggesting a change in plasticity rather
      than a momentary facilitation of behavior. OBJECTIVES/METHODS: Although the
      mechanism of HFS-enhanced learning is not understood, evidence suggests that
      dopamine plays a critical role. Therefore, we used in vivo amperometry to
      evaluate the effects of HFS on striatal dopamine release in the anesthetized
      primate. While this does not directly examine dopamine during learning, it
      provides insight with relation to dopamine dynamics during electrical stimulation
      and specifically between different stimulation parameters and striatal
      compartments. RESULTS: We demonstrate that HFS results in significantly more
      dopamine release in the striatum compared to low-frequency stimulation. In
      addition, electrical stimulation operates differentially on specific neuronal
      elements, as the parameters for dopamine release are different for the caudate,
      putamen and medial forebrain bundle. CONCLUSIONS: While not direct evidence,
      these data suggest that HFS evokes significant dopamine release which may play a
      role in stimulation-enhanced learning. Moreover, these data suggest a means to
      modulate extracellular dopamine with a high degree of temporal and spatial
      precision for either research or clinical applications.

PMID- 24107984
TI  - Context-driven, prescription-based personal activity classification: methodology,
      architecture, and end-to-end implementation.
AB  - Enabling large-scale monitoring and classification of a range of motion
      activities is of primary importance due to the need by healthcare and fitness
      professionals to monitor exercises for quality and compliance. Past work has not
      fully addressed the unique challenges that arise from scaling. This paper
      presents a novel end-to-end system solution to some of these challenges. The
      system is built on the prescription-based context-driven activity classification
      methodology. First, we show that by refining the definition of context, and
      introducing the concept of scenarios, a prescription model can provide
      personalized activity monitoring. Second, through a flexible architecture
      constructed from interface models, we demonstrate the concept of a context-driven
      classifier. Context classification is achieved through a classification committee
      approach, and activity classification follows by means of context specific
      activity models. Then, the architecture is implemented in an end-to-end system
      featuring an Android application running on a mobile device, and a number of
      classifiers as core classification components. Finally, we use a series of
      experimental field evaluations to confirm the expected benefits of the proposed
      system in terms of classification accuracy, rate, and sensor operating life. 

PMID- 24107985
TI  - Automatic handling of tissue microarray cores in high-dimensional microscopy
      images.
AB  - This paper describes a specific tool for automatically segmenting and archiving
      of tissue microarray (TMA) cores in microscopy images at different
      magnifications. TMA enables researchers to extract the small cylinders of a
      single tissue (core sections) from histological sections and arrange them in an
      array on a paraffin block such that hundreds can be analyzed simultaneously. A
      crucial step to improve the speed and quality of this process is the correct
      localization of each tissue core in the array. However, usually the tissue cores
      are not aligned in the microarray, the TMA cores are incomplete and the images
      are noisy and with distorted colors. We develop a robust framework to handle core
      sections under these conditions. The algorithms are able to detect, stitch, and
      archive the TMA cores at different magnifications. Once the TMA cores are
      segmented they are stored in a relational database allowing their processing for
      further studies of benign-malignant classification. The method was shown to be
      reliable for handling the TMA cores and therefore enabling further large-scale
      molecular pathology research. 

PMID- 24107986
TI  - Design of a RESTful web information system for drug prescription and
      administration.
AB  - Drug prescription and administration processes strongly impact on the occurrence
      of risks in medical settings for they can be sources of adverse drug events
      (ADEs). A properly engineered use of information and communication technologies
      has proven to be a promising approach to reduce these risks. In this study, we
      propose PHARMA, a web information system which supports healthcare staff in the
      secure cooperative execution of drug prescription, transcription and registration
      tasks. PHARMA allows the easy sharing and management of documents containing drug
      related information (i.e., drug prescriptions, medical reports, screening), which
      is often inconsistent and scattered across different information systems and
      heterogeneous organization domains (e.g., departments, other hospital
      facilities). PHARMA enables users to access such information in a consistent and
      secure way, through the adoption of REST and web-oriented design paradigms and
      protocols. We describe the implementation of the PHARMA prototype, and we discuss
      the results of the usability evaluation that we carried out with the staff of a
      hospital in Florence, Italy. 

PMID- 24107987
TI  - Robust and sensitive video motion detection for sleep analysis.
AB  - In this paper, we propose a camera-based system combining video motion detection,
      motion estimation, and texture analysis with machine learning for sleep analysis.
      The system is robust to time-varying illumination conditions while using standard
      camera and infrared illumination hardware. We tested the system for periodic limb
      movement (PLM) detection during sleep, using EMG signals as a reference. We
      evaluated the motion detection performance both per frame and with respect to
      movement event classification relevant for PLM detection. The Matthews
      correlation coefficient improved by a factor of 2, compared to a state-of-the-art
      motion detection method, while sensitivity and specificity increased with 45% and
      15%, respectively. Movement event classification improved by a factor of 6 and 3
      in constant and highly varying lighting conditions, respectively. On 11 PLM
      patient test sequences, the proposed system achieved a 100% accurate PLM index
      (PLMI) score with a slight temporal misalignment of the starting time (<1 s)
      regarding one movement. We conclude that camera-based PLM detection during sleep
      is feasible and can give an indication of the PLMI score.

PMID- 24107989
TI  - Current Opinion in Clinical Nutrition and Metabolic Care. Editorial
      introductions.

PMID- 24107988
TI  - Link-state-estimation-based transmission power control in wireless body area
      networks.
AB  - This paper presents a novel transmission power control protocol to extend the
      lifetime of sensor nodes and to increase the link reliability in wireless body
      area networks (WBANs). We first experimentally investigate the properties of the
      link states using the received signal strength indicator (RSSI). We then propose
      a practical transmission power control protocol based on both short- and long
      term link-state estimations. Both the short- and long-term link-state estimations
      enable the transceiver to adapt the transmission power level and target the RSSI
      threshold range, respectively, to simultaneously satisfy the requirements of
      energy efficiency and link reliability. Finally, the performance of the proposed
      protocol is experimentally evaluated in two experimental scenarios-body posture
      change and dynamic body motion-and compared with the typical WBAN transmission
      power control protocols, a real-time reactive scheme, and a dynamic postural
      position inference mechanism. From the experimental results, it is found that the
      proposed protocol increases the lifetime of the sensor nodes by a maximum of
      9.86% and enhances the link reliability by reducing the packet loss by a maximum
      of 3.02%.

PMID- 24107990
TI  - Meiotic chromosome structures constrain and respond to designation of crossover
      sites.
AB  - Crossover recombination events between homologous chromosomes are required to
      form chiasmata, temporary connections between homologues that ensure their proper
      segregation at meiosis I. Despite this requirement for crossovers and an excess
      of the double-strand DNA breaks that are the initiating events for meiotic
      recombination, most organisms make very few crossovers per chromosome pair.
      Moreover, crossovers tend to inhibit the formation of other crossovers nearby on
      the same chromosome pair, a poorly understood phenomenon known as crossover
      interference. Here we show that the synaptonemal complex, a meiosis-specific
      structure that assembles between aligned homologous chromosomes, both constrains
      and is altered by crossover recombination events. Using a cytological marker of
      crossover sites in Caenorhabditis elegans, we show that partial depletion of the
      synaptonemal complex central region proteins attenuates crossover interference,
      increasing crossovers and reducing the effective distance over which interference
      operates, indicating that synaptonemal complex proteins limit crossovers.
      Moreover, we show that crossovers are associated with a local 0.4-0.5-micrometre
      increase in chromosome axis length. We propose that meiotic crossover regulation
      operates as a self-limiting system in which meiotic chromosome structures
      establish an environment that promotes crossover formation, which in turn alters
      chromosome structure to inhibit other crossovers at additional sites. 

PMID- 24107991
TI  - Multiple sclerosis: An old drug plays a new trick.

PMID- 24107992
TI  - DNMT1-interacting RNAs block gene-specific DNA methylation.
AB  - DNA methylation was first described almost a century ago; however, the rules
      governing its establishment and maintenance remain elusive. Here we present data
      demonstrating that active transcription regulates levels of genomic methylation.
      We identify a novel RNA arising from the CEBPA gene locus that is critical in
      regulating the local DNA methylation profile. This RNA binds to DNMT1 and
      prevents CEBPA gene locus methylation. Deep sequencing of transcripts associated
      with DNMT1 combined with genome-scale methylation and expression profiling extend
      the generality of this finding to numerous gene loci. Collectively, these results
      delineate the nature of DNMT1-RNA interactions and suggest strategies for gene
      selective demethylation of therapeutic targets in human diseases. 

PMID- 24107993
TI  - Visualizing virus assembly intermediates inside marine cyanobacteria.
AB  - Cyanobacteria are photosynthetic organisms responsible for ~25% of organic carbon
      fixation on the Earth. These bacteria began to convert solar energy and carbon
      dioxide into bioenergy and oxygen more than two billion years ago. Cyanophages,
      which infect these bacteria, have an important role in regulating the marine
      ecosystem by controlling cyanobacteria community organization and mediating
      lateral gene transfer. Here we visualize the maturation process of cyanophage
      Syn5 inside its host cell, Synechococcus, using Zernike phase contrast electron
      cryo-tomography (cryoET). This imaging modality yields dramatic enhancement of
      image contrast over conventional cryoET and thus facilitates the direct
      identification of subcellular components, including thylakoid membranes,
      carboxysomes and polyribosomes, as well as phages, inside the congested cytosol
      of the infected cell. By correlating the structural features and relative
      abundance of viral progeny within cells at different stages of infection, we
      identify distinct Syn5 assembly intermediates. Our results indicate that the
      procapsid releases scaffolding proteins and expands its volume at an early stage
      of genome packaging. Later in the assembly process, we detected full particles
      with a tail either with or without an additional horn. The morphogenetic pathway
      we describe here is highly conserved and was probably established long before
      that of double-stranded DNA viruses infecting more complex organisms. 

PMID- 24107994
TI  - Arteriolar niches maintain haematopoietic stem cell quiescence.
AB  - Cell cycle quiescence is a critical feature contributing to haematopoietic stem
      cell (HSC) maintenance. Although various candidate stromal cells have been
      identified as potential HSC niches, the spatial localization of quiescent HSCs in
      the bone marrow remains unclear. Here, using a novel approach that combines whole
      mount confocal immunofluorescence imaging techniques and computational modelling
      to analyse significant three-dimensional associations in the mouse bone marrow
      among vascular structures, stromal cells and HSCs, we show that quiescent HSCs
      associate specifically with small arterioles that are preferentially found in
      endosteal bone marrow. These arterioles are ensheathed exclusively by rare NG2
      (also known as CSPG4)(+) pericytes, distinct from sinusoid-associated leptin
      receptor (LEPR)(+) cells. Pharmacological or genetic activation of the HSC cell
      cycle alters the distribution of HSCs from NG2(+) periarteriolar niches to
      LEPR(+) perisinusoidal niches. Conditional depletion of NG2(+) cells induces HSC
      cycling and reduces functional long-term repopulating HSCs in the bone marrow.
      These results thus indicate that arteriolar niches are indispensable for
      maintaining HSC quiescence. 

PMID- 24107995
TI  - A regenerative approach to the treatment of multiple sclerosis.
AB  - Progressive phases of multiple sclerosis are associated with inhibited
      differentiation of the progenitor cell population that generates the mature
      oligodendrocytes required for remyelination and disease remission. To identify
      selective inducers of oligodendrocyte differentiation, we performed an image
      based screen for myelin basic protein (MBP) expression using primary rat optic
      nerve-derived progenitor cells. Here we show that among the most effective
      compounds identifed was benztropine, which significantly decreases clinical
      severity in the experimental autoimmune encephalomyelitis (EAE) model of
      relapsing-remitting multiple sclerosis when administered alone or in combination
      with approved immunosuppressive treatments for multiple sclerosis. Evidence from
      a cuprizone-induced model of demyelination, in vitro and in vivo T-cell assays
      and EAE adoptive transfer experiments indicated that the observed efficacy of
      this drug results directly from an enhancement of remyelination rather than
      immune suppression. Pharmacological studies indicate that benztropine functions
      by a mechanism that involves direct antagonism of M1 and/or M3 muscarinic
      receptors. These studies should facilitate the development of effective new
      therapies for the treatment of multiple sclerosis that complement established
      immunosuppressive approaches. 

PMID- 24107996
TI  - Feature detection and orientation tuning in the Drosophila central complex.
AB  - Many animals, including insects, are known to use visual landmarks to orient in
      their environment. In Drosophila melanogaster, behavioural genetics studies have
      identified a higher brain structure called the central complex as being required
      for the fly's innate responses to vertical visual features and its short- and
      long-term memory for visual patterns. But whether and how neurons of the fly
      central complex represent visual features are unknown. Here we use two-photon
      calcium imaging in head-fixed walking and flying flies to probe visuomotor
      responses of ring neurons--a class of central complex neurons that have been
      implicated in landmark-driven spatial memory in walking flies and memory for
      visual patterns in tethered flying flies. We show that dendrites of ring neurons
      are visually responsive and arranged retinotopically. Ring neuron receptive
      fields comprise both excitatory and inhibitory subfields, resembling those of
      simple cells in the mammalian primary visual cortex. Ring neurons show strong
      and, in some cases, direction-selective orientation tuning, with a notable
      preference for vertically oriented features similar to those that evoke innate
      responses in flies. Visual responses were diminished during flight, but, in
      contrast with the hypothesized role of the central complex in the control of
      locomotion, not modulated during walking. Taken together, these results indicate
      that ring neurons represent behaviourally relevant visual features in the fly's
      environment, enabling downstream central complex circuits to produce appropriate
      motor commands. More broadly, this study opens the door to mechanistic
      investigations of circuit computations underlying visually guided action
      selection in the Drosophila central complex.

PMID- 24107998
TI  - Silver enhanced TiO2 thin films: photocatalytic characterization using aqueous
      solutions of tris(hydroxymethyl)aminomethane.
AB  - The photocatalytic activity in aqueous solutions of TiO2 and Ag enhanced TiO2 sol
      gel produced films was characterized using tris(hydroxymethyl)aminomethane (Tris)
      under black light (365 nm) and the observed differences in efficiency were
      further investigated by O2 adsorption studies using the same probe. Hydrogen
      abstracting species, such as hydroxyl radicals formed upon photocatalysis, are
      able to abstract hydrogen from Tris. This reaction leads to the formation of
      formaldehyde which was detected and quantified through a modified version of the
      Hantzsch reaction. It was found that the Ag enhanced TiO2 film increased the
      apparent quantum yield from 7% to 12%, partly as a result of a Schottky barrier
      formation at the metal-semiconductor interface and partly as the sensitizing
      effect of Ag nanoparticles extends the visible light absorption, which through
      electron transfer processes enable an efficient charge separation in the TiO2 by
      attracting acceptor species more efficiently than pure TiO2. The O2 adsorption
      studies in this paper showed that the Ag enhanced TiO2 film has a stronger
      adsorption affinity than pure TiO2 towards O2, which make the reduction of O2
      more efficient with a subsequent enhanced electron-hole lifetime. It was also
      found that the Ag enhanced TiO2 film had a poorer adsorption affinity for Tris
      than the pure TiO2 film, which is a consequence of fewer available surface
      adsorption sites due to the Ag coverage at 64% which agrees well with the
      obtained adsorption equilibrium constants (K(LH(TiO2)) = 615 M(-1) and K(LH(Ag
      TiO2)) = 320 M(-1)).

PMID- 24107997
TI  - Integrin-modulating therapy prevents fibrosis and autoimmunity in mouse models of
      scleroderma.
AB  - In systemic sclerosis (SSc), a common and aetiologically mysterious form of
      scleroderma (defined as pathological fibrosis of the skin), previously healthy
      adults acquire fibrosis of the skin and viscera in association with
      autoantibodies. Familial recurrence is extremely rare and causal genes have not
      been identified. Although the onset of fibrosis in SSc typically correlates with
      the production of autoantibodies, whether they contribute to disease pathogenesis
      or simply serve as a marker of disease remains controversial and the mechanism
      for their induction is largely unknown. The study of SSc is hindered by a lack of
      animal models that recapitulate the aetiology of this complex disease. To gain a
      foothold in the pathogenesis of pathological skin fibrosis, we studied stiff skin
      syndrome (SSS), a rare but tractable Mendelian disorder leading to childhood
      onset of diffuse skin fibrosis with autosomal dominant inheritance and complete
      penetrance. We showed previously that SSS is caused by heterozygous missense
      mutations in the gene (FBN1) encoding fibrillin-1, the main constituent of
      extracellular microfibrils. SSS mutations all localize to the only domain in
      fibrillin-1 that harbours an Arg-Gly-Asp (RGD) motif needed to mediate cell
      matrix interactions by binding to cell-surface integrins. Here we show that mouse
      lines harbouring analogous amino acid substitutions in fibrillin-1 recapitulate
      aggressive skin fibrosis that is prevented by integrin-modulating therapies and
      reversed by antagonism of the pro-fibrotic cytokine transforming growth factor
      beta (TGF-beta). Mutant mice show skin infiltration of pro-inflammatory immune
      cells including plasmacytoid dendritic cells, T helper cells and plasma cells,
      and also autoantibody production; these findings are normalized by integrin
      modulating therapies or TGF-beta antagonism. These results show that alterations
      in cell-matrix interactions are sufficient to initiate and sustain inflammatory
      and pro-fibrotic programmes and highlight new therapeutic strategies. 

PMID- 24107999
TI  - An observational study of extracorporeal CPR for in-hospital cardiac arrest
      secondary to myocardial infarction.
AB  - OBJECTIVE: To determine the effects of extracorporeal cardiopulmonary
      resuscitation (ECPR) in patients with in-hospital cardiac arrest (IHCA) due to
      acute myocardial infarction (AMI). METHODS: IHCA patients due to AMI undergoing
      CPR between 1 January 2006 and 1 July 2010 were analysed retrospectively. We
      compared the survival outcome of 43 patients who received ECPR with that of 23
      patients who underwent conventional CPR. RESULTS: The survival rate was 34.9% for
      patients who received ECPR and 21.8% for those who received conventional CPR
      (p=0.4). Increased survival rates to hospital discharge were seen in patients
      with ST segment elevation (p<0.01), or had initial rhythm of ventricular
      tachycardia/ventricular fibrillation (VT/VF) during resuscitation (p=0.031).
      CONCLUSIONS: ECPR may improve survival in cardiac arrest patients who have a ST
      segment elevation or initial rhythm of VT/VF myocardial infarction.

PMID- 24108000
TI  - Expanding the concept of safety in psychiatric inpatient units to create healing
      environments.

PMID- 24108001
TI  - "Recovery" as a concept for PACT clients or other mental health clients.

PMID- 24108002
TI  - SOS based robust H(infinity) fuzzy dynamic output feedback control of nonlinear
      networked control systems.
AB  - In this paper, a methodology for designing a fuzzy dynamic output feedback
      controller for discrete-time nonlinear networked control systems is presented
      where the nonlinear plant is modelled by a Takagi-Sugeno fuzzy model and the
      network-induced delays by a finite state Markov process. The transition
      probability matrix for the Markov process is allowed to be partially known,
      providing a more practical consideration of the real world. Furthermore, the
      fuzzy controller's membership functions and premise variables are not assumed to
      be the same as the plant's membership functions and premise variables, that is,
      the proposed approach can handle the case, when the premise of the plant are not
      measurable or delayed. The membership functions of the plant and the controller
      are approximated as polynomial functions, then incorporated into the controller
      design. Sufficient conditions for the existence of the controller are derived in
      terms of sum of square inequalities, which are then solved by YALMIP. Finally, a
      numerical example is used to demonstrate the validity of the proposed
      methodology. 

PMID- 24108004
TI  - In vitro detection of calcium in bone by modified carbon dots.
AB  - This article depicts a simple and novel approach to locate calcium deposits in
      bone using modified carbon dots (CDs) through fluorescence imaging. Amino
      functionalized CDs along with glutamic acid, a naturally-occurring ligand for
      calcium ions, were conjugated onto hyaluronic acid using EDC chemistry. The
      ability of the probe to recognise Ca ions was demonstrated using polymer strips
      doped with Ca ions and freshly collected bones. The probe was found to bind more
      at bone cracks, reflecting its potential to locate micro-cracks in bone as well
      as to map Ca deposits. The bound portions can be visualized through a
      fluorescence microscope or by illumination by a UV source (365 nm). The
      components used to generate the probes, namely CD, glutamic acid and hyaluronic
      acid, are well known for their non-toxicity and biocompatibility. It appears,
      therefore, that the probe could be used for in vivo applications. 

PMID- 24108003
TI  - Enhanced autophagy blocks angiogenesis via degradation of gastrin-releasing
      peptide in neuroblastoma cells.
AB  - Neuroblastoma is characterized by florid vascularization leading to rapid tumor
      dissemination to distant organs; angiogenesis contributes to tumor progression
      and poor clinical outcomes. We have previously demonstrated an increased
      expression of gastrin-releasing peptide (GRP) and its receptor, GRPR, in
      neuroblastoma and that GRP activates the PI3K-AKT pathway as a proangiogenic
      factor during tumor progression. Interestingly, AKT activation phosphorylates
      MTOR, a critical negative regulator of autophagy, a cellular process involved in
      the degradation of key proteins. We hypothesize that inhibition of GRPR enhances
      autophagy-mediated degradation of GRP and subsequent inhibition of angiogenesis
      in neuroblastoma. Here, we demonstrated a novel phenomenon where targeting GRPR
      using shRNA or a specific antagonist, RC-3095, decreased GRP secretion by
      neuroblastoma cells and tubule formation by endothelial cells in vitro.
      Furthermore, shGRPR or RC-3095 treatment enhanced expression of proautophagic
      proteins in human neuroblastoma cell lines, BE(2)-C, and BE(2)-M17.
      Interestingly, rapamycin, an inhibitor of MTOR, enhanced the expression of the
      autophagosomal marker LC3-II and GRP was localized within LC3-II-marked
      autophagosomes in vitro as well as in vivo, indicating autophagy-mediated
      degradation of GRP. Moreover, overexpression of ATG5 or BECN1 attenuated GRP
      secretion and tubule formation, whereas opposite effects were observed with siRNA
      silencing of ATG5 and BECN1. Our data supported the role of autophagy in the
      degradation of GRP and subsequent inhibition of angiogenesis. Therefore,
      activation of autophagy may lead to novel antivascular therapeutic strategies in
      the treatment of highly vascular neuroblastomas. 

PMID- 24108008
TI  - Copper catalyzed synthesis of fused benzimidazolopyrazine derivatives via tandem
      benzimidazole formation/annulation of delta-alkynyl aldehyde.
AB  - A novel route to synthesize the biologically active benzimidazolopyrazine core is
      outlined. The reaction proceeds via tandem benzimidazole formation/annulations of
      indole, pyrrole and aliphatic delta-alkynyl aldehydes in the presence of copper
      salts and green solvents with moderate to good yields. 

PMID- 24108005
TI  - Photochemical reflectance index as an indirect estimator of foliar isoprenoid
      emissions at the ecosystem level.
AB  - Terrestrial plants re-emit around 1-2% of the carbon they fix as isoprene and
      monoterpenes. These emissions have major roles in the ecological relationships
      among living organisms and in atmospheric chemistry and climate, and yet their
      actual quantification at the ecosystem level in different regions is far from
      being resolved with available models and field measurements. Here we provide
      evidence that a simple remote sensing index, the photochemical reflectance index,
      which is indicative of light use efficiency, is a good indirect estimator of
      foliar isoprenoid emissions and can therefore be used to sense them remotely.
      These results open new perspectives for the potential use of remote sensing
      techniques to track isoprenoid emissions from vegetation at larger scales. On the
      other hand, our study shows the potential of this photochemical reflectance index
      technique to validate the availability of photosynthetic reducing power as a
      factor involved in isoprenoid production. 

PMID- 24108011
TI  - Modulated photoluminescence of graphene quantum dots in the vicinity of an
      individual silver nano-octahedron.
AB  - We propose an effective strategy to enhance and modulate the photoluminescence
      (PL) of graphene quantum dots (GQDs) in the vicinity of a single silver nano
      octahedron (SNO) utilizing three-dimensional finite-difference time-domain
      calculations. The SNO is designed to act as a multifrequency plasmonic antenna
      with multiple plasmon resonance modes covering multiple emission peaks of GQDs.
      The spectral modifications of spontaneous emission are investigated with the
      variations of the GQD's position and dipole moment orientation relative to the
      SNO. The PL colour of the GQD can be precisely adjusted between blue and green
      through the strong interaction with the designed antenna. The multicolour
      features of GQDs will also facilitate their potential applications as eco
      friendly and multifunctional optical probes. The study contributes to a deeper
      understanding of the PL properties of GQDs near the metallic nanoparticles. 

PMID- 24108012
TI  - Improving genome understanding.

PMID- 24108025
TI  - Cell transport carries off Nobel.

PMID- 24108026
TI  - Higgs theorists amass physics prize.

PMID- 24108027
TI  - Congo carbon plan kicks off.

PMID- 24108028
TI  - Researchers split over NSA hacking.

PMID- 24108029
TI  - Novartis reboots brain division.

PMID- 24108030
TI  - Secrets of trial data revealed.

PMID- 24108031
TI  - Neuroscience: Through the eyes of a mouse.

PMID- 24108032
TI  - Amazon ecology: Footprints in the forest.

PMID- 24108037
TI  - Sustainability: Reduce, reuse and recycle lab waste.

PMID- 24108038
TI  - Engineering: Biologists borrow more than words.

PMID- 24108039
TI  - Biodiversity: Oil-palm replanting raises ecology issues.

PMID- 24108040
TI  - Environment: Understanding our destructive choices.

PMID- 24108041
TI  - Academic support: Celebrating 80 years of science solidarity.

PMID- 24108042
TI  - Medical research: Analyse impact of health priorities.

PMID- 24108043
TI  - Horizon 2020: A call to forge biodiversity links.

PMID- 24108044
TI  - Data deposition: Fees could damage public data archives.

PMID- 24108045
TI  - Peter Huttenlocher (1931-2013).

PMID- 24108046
TI  - Earth science: The timing of climate change.

PMID- 24108047
TI  - Quantum physics: Watching the wavefunction collapse.

PMID- 24108049
TI  - Metabolic syndrome: F stands for fructose and fat.

PMID- 24108050
TI  - The projected timing of climate departure from recent variability.
AB  - Ecological and societal disruptions by modern climate change are critically
      determined by the time frame over which climates shift beyond historical
      analogues. Here we present a new index of the year when the projected mean
      climate of a given location moves to a state continuously outside the bounds of
      historical variability under alternative greenhouse gas emissions scenarios.
      Using 1860 to 2005 as the historical period, this index has a global mean of 2069
      (+/-18 years s.d.) for near-surface air temperature under an emissions
      stabilization scenario and 2047 (+/-14 years s.d.) under a 'business-as-usual'
      scenario. Unprecedented climates will occur earliest in the tropics and among low
      income countries, highlighting the vulnerability of global biodiversity and the
      limited governmental capacity to respond to the impacts of climate change. Our
      findings shed light on the urgency of mitigating greenhouse gas emissions if
      climates potentially harmful to biodiversity and society are to be prevented. 

PMID- 24108051
TI  - Evidence for a new nuclear 'magic number' from the level structure of 54Ca.
AB  - Atomic nuclei are finite quantum systems composed of two distinct types of
      fermion--protons and neutrons. In a manner similar to that of electrons orbiting
      in an atom, protons and neutrons in a nucleus form shell structures. In the case
      of stable, naturally occurring nuclei, large energy gaps exist between shells
      that fill completely when the proton or neutron number is equal to 2, 8, 20, 28,
      50, 82 or 126 (ref. 1). Away from stability, however, these so-called 'magic
      numbers' are known to evolve in systems with a large imbalance of protons and
      neutrons. Although some of the standard shell closures can disappear, new ones
      are known to appear. Studies aiming to identify and understand such behaviour are
      of major importance in the field of experimental and theoretical nuclear physics.
      Here we report a spectroscopic study of the neutron-rich nucleus (54)Ca (a bound
      system composed of 20 protons and 34 neutrons) using proton knockout reactions
      involving fast radioactive projectiles. The results highlight the doubly magic
      nature of (54)Ca and provide direct experimental evidence for the onset of a
      sizable subshell closure at neutron number 34 in isotopes far from stability.

PMID- 24108052
TI  - Observing single quantum trajectories of a superconducting quantum bit.
AB  - The length of time that a quantum system can exist in a superposition state is
      determined by how strongly it interacts with its environment. This interaction
      entangles the quantum state with the inherent fluctuations of the environment. If
      these fluctuations are not measured, the environment can be viewed as a source of
      noise, causing random evolution of the quantum system from an initially pure
      state into a statistical mixture--a process known as decoherence. However, by
      accurately measuring the environment in real time, the quantum system can be
      maintained in a pure state and its time evolution described by a 'quantum
      trajectory' determined by the measurement outcome. Here we use weak measurements
      to monitor a microwave cavity containing a superconducting quantum bit (qubit),
      and track the individual quantum trajectories of the system. In this set-up, the
      environment is dominated by the fluctuations of a single electromagnetic mode of
      the cavity. Using a near-quantum-limited parametric amplifier, we selectively
      measure either the phase or the amplitude of the cavity field, and thereby
      confine trajectories to either the equator or a meridian of the Bloch sphere. We
      perform quantum state tomography at discrete times along the trajectory to verify
      that we have faithfully tracked the state of the quantum system as it diffuses on
      the surface of the Bloch sphere. Our results demonstrate that decoherence can be
      mitigated by environmental monitoring, and validate the foundation of quantum
      feedback approaches based on Bayesian statistics. Moreover, our experiments
      suggest a new means of implementing 'quantum steering'--the harnessing of action
      at a distance to manipulate quantum states through measurement.

PMID- 24108053
TI  - Quasicrystalline structure formation in a classical crystalline thin-film system.
AB  - The discovery of quasicrystals--crystalline structures that show order while
      lacking periodicity--forced a paradigm shift in crystallography. Initially
      limited to intermetallic systems, the observation of quasicrystalline structures
      has recently expanded to include 'soft' quasicrystals in the fields of colloidal
      and supermolecular chemistry. Here we report an aperiodic oxide that grows as a
      two-dimensional quasicrystal on a periodic single-element substrate. On a Pt(111)
      substrate with 3-fold symmetry, the perovskite barium titanate BaTiO3 forms a
      high-temperature interface-driven structure with 12-fold symmetry. The building
      blocks of this dodecagonal structure assemble with the theoretically predicted
      Stampfli-Gahler tiling having a fundamental length-scale of 0.69 nm. This example
      of interface-driven formation of ultrathin quasicrystals from a typical periodic
      perovskite oxide potentially extends the quasicrystal concept to a broader range
      of materials. In addition, it demonstrates that frustration at the interface
      between two periodic materials can drive a thin film into an aperiodic
      quasicrystalline phase, as proposed previously. Such structures might also find
      use as ultrathin buffer layers for the accommodation of large lattice mismatches
      in conventional epitaxy.

PMID- 24108054
TI  - Bottom-up control of geomagnetic secular variation by the Earth's inner core.
AB  - Temporal changes in the Earth's magnetic field, known as geomagnetic secular
      variation, occur most prominently at low latitudes in the Atlantic hemisphere
      (that is, from -90 degrees east to 90 degrees east), whereas in the Pacific
      hemisphere there is comparatively little activity. This is a consequence of the
      geographical localization of intense, westward drifting, equatorial magnetic flux
      patches at the core surface. Despite successes in explaining the morphology of
      the geomagnetic field, numerical models of the geodynamo have so far failed to
      account systematically for this striking pattern of geomagnetic secular
      variation. Here we show that it can be reproduced provided that two mechanisms
      relying on the inner core are jointly considered. First, gravitational coupling
      aligns the inner core with the mantle, forcing the flow of liquid metal in the
      outer core into a giant, westward drifting, sheet-like gyre. The resulting shear
      concentrates azimuthal magnetic flux at low latitudes close to the core-mantle
      boundary, where it is expelled by core convection and subsequently transported
      westward. Second, differential inner-core growth, fastest below Indonesia, causes
      an asymmetric buoyancy release in the outer core which in turn distorts the gyre,
      forcing it to become eccentric, in agreement with recent core flow inversions.
      This bottom-up heterogeneous driving of core convection dominates top-down
      driving from mantle thermal heterogeneities, and localizes magnetic variations in
      a longitudinal sector centred beneath the Atlantic, where the eccentric gyre
      reaches the core surface. To match the observed pattern of geomagnetic secular
      variation, the solid material forming the inner core must now be in a state of
      differential growth rather than one of growth and melting induced by convective
      translation. 

PMID- 24108058
TI  - Deep brain stimulation for movement disorders: what counts in the end is the end
      result.

PMID- 24108059
TI  - De novo psychosis in a new onset Parkinson disease.

PMID- 24108060
TI  - Dysfunctional family environment in affected versus unaffected offspring of
      parents with bipolar disorder.
AB  - OBJECTIVE: Children of parents with bipolar disorder (BD) are at heightened risk
      for developing mood and other psychiatric disorders. We proposed to evaluate the
      environment of families with at least one parent with BD type I (BDF) with
      affected offspring (aBDF) and unaffected offspring (uBDF) compared with control
      families without a history of DSM-IV Axis I disorder (CF). METHOD: We used the
      Family Environment Scale (FES) to evaluate 47 BDF (aBDF + uBDF) and 30 CF.
      Parents were assessed through the Structured Clinical Interview for DSM-IV Axis I
      Disorders (SCID-I). Diagnosis of the offspring was determined through the
      Schedule for Affective Disorders and Schizophrenia for School-Age
      Children/Present and Lifetime Version (K-SADS-PL) interview. RESULTS: There were
      statistically significant differences between aBDF, uBDF and CF in cohesion (p =
      0.003), intellectual-cultural orientation (p = 0.01), active-recreational
      orientation (p = 0.007), conflict (p = 0.001), control (p = 0.01), moral
      religious emphasis (p = 0.01) and organization (p = 0.001). The aBDF showed
      higher levels of control (p = 0.02) when compared to the uBDF. CONCLUSIONS:
      Families with a BD parent presented more dysfunctional interactions among
      members. Moreover, the presence of BD or other psychiatric disorders in the
      offspring of parents with BD is associated with higher levels of control. These
      results highlight the relevance of psychosocial interventions to improve
      resilience and family interactions.

PMID- 24108061
TI  - Versatile N2S2 nickel-dithiolates as mono- and bridging bidentate, S-donor
      ligands to gold(I).
AB  - Development of square planar cis-dithiolate nickel complexes as metallo S-donor
      ligands focuses on the synthesis and structures of gold(I) heterometallic
      clusters derived from assemblage with three NiN2S2 complexes: Ni(bme-daco),
      Ni(bme-dach) and Ni(ema)(2-) (bme-daco = (bismercaptoethanediazacyclooctane); bme
      dach = bismercaptoethanediazacycloheptane; and ema = N,N'-ethylenebis-2
      mercaptoacetamide). With Ph3PAuCl as the gold source, examples of simple S
      aurolation retaining the PPh3 on Au(+) were obtained for [{Ni(bme
      daco)}AuPPh3](+)Cl(-) and [{Ni(ema)}2Au4(PPh3)4], where the latter complex
      demonstrated unsupported aurophilic interactions between [{Ni(ema)}Au2(PPh3)2]
      units in its X-ray crystal structure (Au-Au = 3.054 and 3.127 A). Three compounds
      containing fully-supported digold units with Au-Au distances in the aurophilic
      range of 3.11 to 3.13 A were found as stair-step structures in which planar
      NiN2S2 step treads are connected by planar S2Au2S2 risers at ca. 90 degrees :
      [{Ni(bme-daco)}2Au2](2+)(Cl(-))2; [{Ni(bme-dach)}2Au2](2+)(Cl(-))2; and
      (Et4N(+))2[{Ni(ema)}2Au2](2-). Electrochemical data from cyclic voltammograms
      demonstrated a positive shift in Ni(II/I) couples for the [{NiN2S2}xAuy]
      complexes as compared to the NiN2S2 precursors and a ca. 700 mV decrease in
      communication between multiple NiN2S2 units as compared to [{NiN2S2}2Ni](2+)
      analogues in slant chair conformation. The analogy between NiN2S2
      metallodithiolate ligands and diphosphine ligands holds here as in other examples
      of inorganic and organometallic complexes.

PMID- 24108062
TI  - Enhanced peroxydisulfate electrochemiluminescence for dopamine biosensing based
      on Au nanoparticle decorated reduced graphene oxide.
AB  - This work reports a novel strategy to amplify the electrochemiluminescence (ECL)
      signal of peroxydisulfate solution based on the Au nanoparticle decorated reduced
      graphene oxide (Au NP-RGO), and further an ECL biosensor for sensitive and
      selective detection of dopamine (DA) was constructed. Due to the synergistic
      amplification of Au NPs and RGO, the ECL signal of peroxydisulfate solution on
      the Au NP-RGO modified electrode was about 5-fold enhanced compared to that of
      the bare electrode with the ECL onset potential positively shifted from -1.2 V to
      -0.9 V. More interestingly, the ECL intensity of peroxydisulfate solution
      increased with the increase of DA concentration, based on which an ECL biosensor
      for DA determination was fabricated. The as-prepared solid-state ECL DA sensor
      showed a wide linear response of 0.02-40 MUM with a detection limit of 6.7 nM
      (S/N = 3). Moreover, we expect this work would open up a new field in the
      application of peroxydisulfate solution ECL for highly sensitive bioassays. 

PMID- 24108063
TI  - Peel-and-stick: mechanism study for efficient fabrication of flexible/transparent
      thin-film electronics.
AB  - Peel-and-stick process, or water-assisted transfer printing (WTP), represents an
      emerging process for transferring fully fabricated thin-film electronic devices
      with high yield and fidelity from a SiO2/Si wafer to various non-Si based
      substrates, including papers, plastics and polymers. This study illustrates that
      the fundamental working principle of the peel-and-stick process is based on the
      water-assisted subcritical debonding, for which water reduces the critical
      adhesion energy of metal-SiO2 interface by 70 ~ 80%, leading to clean and high
      quality transfer of thin-film electronic devices. Water-assisted subcritical
      debonding is applicable for a range of metal-SiO2 interfaces, enabling the peel
      and-stick process as a general and tunable method for fabricating
      flexible/transparent thin-film electronic devices. 

PMID- 24108064
TI  - Cell-free cartilage engineering approach using hyaluronic acid-polycaprolactone
      scaffolds: a study in vivo.
AB  - Polycaprolactone scaffolds modified with cross-linked hyaluronic acid were
      prepared in order to establish whether a more hydrophilic and biomimetic
      microenvironment benefits the progenitor cells arriving from bone marrow in a
      cell-free tissue-engineering approach. The polycaprolactone and
      polycaprolactone/hyaluronic acid scaffolds were characterized in terms of
      morphology and water absorption capacity. The polycaprolactone and
      polycaprolactone/hyaluronic acid samples were implanted in a chondral defect in
      rabbits; bleeding of the subchondral bone was provoked to generate a spontaneous
      healing response. Repair at 1, 4, 12, and 24 weeks was assessed macroscopically
      using the International Cartilage Repair Society score and the Oswestry
      Arthroscopy Score and microscopically using immunohistological staining for
      collagen type I and type II, and for Ki-67. The presence of hyaluronic acid
      improves scaffold performance, which supports a good repair response without
      biomaterial pre-seeding. 

PMID- 24108065
TI  - Pediatric metabolic syndrome and cell blood counts: bivariate Bayesian modeling.
AB  - Cell blood counts are components of hematological parameters and indicators of
      pro-inflammatory states. They are proposed to be associated with metabolic
      syndrome (MetS). This study aimed to assess the relationship of the white blood
      cell (WBC) and the red blood cell (RBC) counts with components of MetS in the
      pediatric age group. The sample consisted of 300 children (152 boys) aged 6-12
      years. Hierarchical Bayesian analysis of the bivariate Poisson regression model
      was used to estimate the effect of various components of MetS according to the
      cell blood counts. We found that RBC and WBC counts were correlated with the
      fasting blood glucose, the waist-to-height ratio, serum triglycerides and the
      blood pressure levels adjusted for age, the body mass index, gender, total
      cholesterol, low-density lipoprotein cholesterol and the hip circumference. The
      high-density lipoprotein cholesterol was correlated with the RBC counts based on
      95% high posterior density regions for parameters in the Bayesian model. Our
      findings may serve as confirmatory evidence for the beginning of inflammatory
      process related to the cardio-metabolic factors from early life. 

PMID- 24108066
TI  - Treatment of intractable anorexia nervosa with inactivation of the nucleus
      accumbens using stereotactic surgery.
AB  - BACKGROUND: For 30% of anorexia nervosa (AN) patients, conventional treatments
      are unsuccessful; this is termed intractable AN. OBJECTIVES: This study
      investigates whether ablation of the nucleus accumbens (NAc) using stereotactic
      surgery can arouse the physiological drive to eat in intractable AN patients.
      METHODS: Eight patients with intractable AN were included: 6 patients underwent
      bilateral stereotactic radio frequency ablation in the NAc and 2 patients
      received bilateral NAc deep brain stimulation (DBS). Observations were made for
      basic vital signs, body mass index (BMI), menstruation, depression, anxiety,
      obsessive-compulsive disorder, personality, intelligence, memory, quality of
      life, social functioning, as well as complications and adverse events associated
      with the treatment. RESULTS: Basic vital signs, BMI and menstruation had
      recovered 1 year after the operation. Depression, anxiety and obsessive
      compulsive disorder were improved 1 year postoperatively. There were changes in
      personality scores for psychoticism, neuroticism and lie tendencies that seemed
      to be helpful to the recovery from AN. Intelligence and memory improved after 6
      months postoperatively. Quality of life and social functioning were dramatically
      improved at 1 year postoperatively. CONCLUSIONS: The results of this study reveal
      that ablation of the NAc can increase the AN patients' physiological drive to
      eat. Furthermore, there were no severe and/or life-influencing complications
      associated with the treatment.

PMID- 24108067
TI  - Simvastatin treatment highlights a new role for the isoprenoid/cholesterol
      biosynthetic pathway in the modulation of emotional reactivity and cognitive
      performance in rats.
AB  - The aim of the present work was to shed light on the role played by the
      isoprenoid/cholesterol biosynthetic pathway in the modulation of emotional
      reactivity and memory consolidation in rodents through the inhibition of the key
      and rate-limiting enzyme 3-hydroxy 3-methylglutaryl Coenzyme A reductase (HMGR)
      both in vivo and in vitro with simvastatin. Three-month-old male Wistar rats
      treated for 21 days with simvastatin or vehicle were tested in the social
      interaction, elevated plus-maze, and inhibitory avoidance tasks; after behavioral
      testing, the amygdala, hippocampus, prefrontal cortex, dorsal, and ventral
      striatum were dissected out for biochemical assays. In order to delve deeper into
      the molecular mechanisms underlying the observed effects, primary rat hippocampal
      neurons were used. Our results show that HMGR inhibition by simvastatin induces
      anxiogenic-like effects in the social interaction but not in the elevated plus
      maze test, and improves memory consolidation in the inhibitory avoidance task.
      These effects are accompanied by imbalances in the activity of specific
      prenylated proteins, Rab3 and RhoA, involved in neurotransmitter release, and
      synaptic plasticity, respectively. Taken together, the present findings indicate
      that the isoprenoid/cholesterol biosynthetic pathway is critically involved in
      the physiological modulation of both emotional and cognitive processes in
      rodents. 

PMID- 24108068
TI  - Syndromic (phenotypic) diarrhoea of infancy/tricho-hepato-enteric syndrome.
AB  - OBJECTIVES: Syndromic diarrhoea/tricho-hepato-enteric syndrome (SD/THE) is a rare
      congenital syndrome. The main features are intractable diarrhoea of infancy, hair
      abnormalities, facial dysmorphism, intrauterine growth restriction and immune
      system abnormalities. It has been linked to abnormalities in two components of
      the putative human ski complex: SKIV2L and TTC37. The long-term outcome of this
      syndrome is still unknown. We aim to describe the long-term outcome, in the
      French cohort of patients born since 1992. DESIGN: Review of the clinical and
      biological features of the 15 patients with SD/THE, followed in France and born
      between 1992 and 2010. RESULTS: All patients presented typical SD/THE syndrome
      features, of intractable diarrhoea in infancy requiring parenteral nutrition, a
      facial dysmorphism with hair abnormalities, and immunological disorders. Half of
      them also had liver and skin abnormalities. Five children died, among which 3
      died due to infections. Probabilities of survival according to the Kaplan-Meier
      method were 93.3%, 86.7%, 74.3 and 61.9%, respectively at 1 year, 5 years, 10
      years and 15 years of age. 3/15 were weaned from parenteral nutrition (PN) with
      likelihood of weaning being 10% at 5 years and 40% at 10 years. At birth 80% were
      small for gestational age and the short stature persisted in 60%. Haemophagocytic
      syndrome was noted in 60% and mild mental retardation was present in 60%.
      CONCLUSIONS: SD/THE is a rare disease with high morbidity and mortality.
      Management should be focused on nutrition and immunological defects.

PMID- 24108070
TI  - Design, synthesis, biological evaluation, and molecular modeling study of 4
      alkoxyquinazoline derivatives as potential VEGFR2 kinase inhibitors.
AB  - A series of novel 4-alkoxyquinazoline derivatives were prepared and synthesized
      and their biological activities were evaluated as potential inhibitors of
      vascular endothelial growth factor receptor 2 (VEGFR2). Of these compounds,
      compound 3j demonstrated the most potent inhibitory activities against VEGFR2
      tyrosine kinase and cell proliferation, the IC50 values of this compound reaching
      up to 2.72 nM and 0.35 MUM, respectively, compared with Tivozanib (3.40 nM and
      0.38 MUM). The obtained results, along with a 3D-QSAR study and molecular docking
      that was used for investigating the probable binding mode, could provide an
      important basis for further optimization of compound 3j as a potential tyrosine
      kinase inhibitor. 

PMID- 24108071
TI  - Growth hormone secretion is correlated with neuromuscular innervation rather than
      motor neuron number in early-symptomatic male amyotrophic lateral sclerosis mice.
AB  - GH deficiency is thought to be involved in the pathogenesis of amyotrophic
      lateral sclerosis (ALS). However, therapy with GH and/or IGF-I has not shown
      benefit. To gain a better understanding of the role of GH secretion in ALS
      pathogenesis, we assessed endogenous GH secretion in wild-type and hSOD1(G93A)
      mice throughout the course of ALS disease. Male wild-type and hSOD1(G93A) mice
      were studied at the presymptomatic, onset, and end stages of disease. To assess
      the pathological features of disease, we measured motor neuron number and
      neuromuscular innervation. We report that GH secretion profile varies at
      different stages of disease progression in hSOD1(G93A) mice; compared with age
      matched controls, GH secretion is unchanged prior to the onset of disease
      symptoms, elevated at the onset of disease symptoms, and reduced at the end stage
      of disease. In hSOD1(G93A) mice at the onset of disease, GH secretion is
      positively correlated with the percentage of neuromuscular innervation but not
      with motor neuron number. Moreover, this occurs in parallel with an elevation in
      the expression of muscle IGF-I relative to controls. Our data imply that
      increased GH secretion at symptom onset may be an endogenous endocrine response
      to increase the local production of muscle IGF-I to stimulate reinnervation of
      muscle, but that in the latter stages of disease this response no longer occurs. 

PMID- 24108069
TI  - Idiopathic vitreomacular traction and macular hole: a comprehensive review of
      pathophysiology, diagnosis, and treatment.
AB  - Posterior vitreous detachment (PVD) is a common phenomenon in the aging eye.
      However, this may be complicated by persistent symptomatic vitreomacular
      adhesions that exert tractional forces on the macula (vitreomacular traction;
      VMT). VMT itself may be associated with epiretinal membrane formation and the
      development of idiopathic macular holes (IMH). Such pathologies may cause visual
      disturbances, including metamorphopsia, photopsia, blurred vision, and decreased
      visual acuity, which impact an individual's quality of life. Technologies such as
      optical coherence tomography allow an increasingly more accurate visualisation of
      the macular anatomy, including quantification of macular hole characteristics,
      and this facilitates treatment decision-making. Pars plana vitrectomy remains the
      primary treatment option for many patients with VMT or IMH; for the latter,
      peeling of the inner limiting membrane (ILM) of the retina has shown improved
      outcomes when compared with no ILM peeling. The development of narrow-gauge
      transconjunctival vitrectomy systems has improved the rate of visual recovery
      following surgery. Ocriplasmin, by degrading laminin and fibronectin at the
      vitreoretinal interface, may allow induction of PVD in a non-invasive manner.
      Indeed, clinical studies have supported its use as an alternative to surgery in
      certain patient populations. However, further research is still needed with
      respect to greater understanding of the pathophysiology underlying the
      development of VMT and IMH. 

PMID- 24108073
TI  - Tuberculosis.

PMID- 24108074
TI  - Diagnosis: Waiting for results.

PMID- 24108072
TI  - Maternal dietary restriction during the periconceptional period in normal-weight
      or obese ewes results in adrenocortical hypertrophy, an up-regulation of the
      JAK/STAT and down-regulation of the IGF1R signaling pathways in the adrenal of
      the postnatal lamb.
AB  - Maternal dietary restriction during the periconceptional period results in an
      increase in adrenal growth and in the cortisol stress response in the offspring.
      The intraadrenal mechanisms that result in the programming of these changes are
      not clear. Activation of the IGF and the signal transducer and activator of
      transcription (STAT)/suppressors of cytokine signaling (SOCS) pathways regulate
      adrenal growth. We have used an embryo transfer model in sheep to investigate the
      impact of exposure to either dietary restriction in normal or obese mothers or to
      maternal obesity during the periconceptional period on adrenal growth and
      function in the offspring. We assessed the adrenal abundance of key signaling
      molecules in the IGF-I and Janus kinase/STAT/SOCS pathways including IGF-I
      receptor, IGF-II receptor, Akt, mammalian target of rapamycin, ribosomal protein
      S6, eukaryotic translation initiation factor 4E-binding protein 1, eukaryotic
      translation initiation factor 4E, STAT1, STAT3, STAT5, SOCS1, and SOCS3 in female
      and male postnatal lambs. Maternal dietary restriction in the periconceptional
      period resulted in the hypertrophy of the adrenocortical cells in the zona
      fasciculata-reticularis and an up-regulation in STAT1, phospho-STAT1, and phospho
      STAT3 (Ser727) abundance and a down-regulation in IGF-I receptor, Akt, and
      phospho-Akt abundance in the adrenal cortex of the postnatal lamb. These studies
      highlight that weight loss around the time of conception, independent of the
      starting maternal body weight, results in the activation of the adrenal Janus
      kinase/STAT pathway and adrenocortical hypertrophy. Thus, signals of adversity
      around the time of conception have a long-term impact on the mechanisms that
      regulate adrenocortical growth. 

PMID- 24108075
TI  - Perspective: Weigh all TB risks.

PMID- 24108076
TI  - Latency: A sleeping giant.

PMID- 24108077
TI  - Transmission: Control issues.

PMID- 24108078
TI  - Epidemiology: A mortal foe.

PMID- 24108079
TI  - Drug development: A combined effort.

PMID- 24108080
TI  - Perspective: Graduation time.

PMID- 24108081
TI  - Vaccines: An age-old problem.

PMID- 24108083
TI  - Early recognition of anti-N-methyl D-aspartate (NMDA) receptor encephalitis
      presenting as acute psychosis.
AB  - OBJECTIVE: We present a case of anti-N-methyl D-aspartate (NMDA) receptor
      encephalitis that illustrates the dilemma that psychiatrists face in evaluating
      patients with first episode psychosis. CONCLUSIONS: The discovery that acute
      psychosis can be the presenting feature of autoimmune encephalitis (in particular
      encephalitis caused by anti-NMDA receptor antibodies) has both practical and
      theoretical consequences. First, this condition is an important, but often
      overlooked, differential diagnosis of first episode psychosis. Antibody testing
      is not currently part of routine screening, though delayed (or missed) diagnosis
      can lead to prolonged hospital stay, medical complications and incomplete or
      delayed recovery. Widespread screening of patients with first presentation
      psychosis for anti-NMDA receptor and anti-voltage-gated potassium channel (anti
      VGKC) antibodies is warranted for a number of reasons: to expedite appropriate
      treatment, to determine the true proportion of patients with these conditions
      presenting as psychosis, and to help elucidate the neurochemical causes of
      psychosis.

PMID- 24108084
TI  - A solution processable fluorene-fluorenone oligomer with aggregation induced
      emission enhancement.
AB  - Herein, we report a novel solution processable fluorenone based small molecule
      with an Aggregation Induced Emission Enhancement (AIEE) property. In contrast to
      previous reports, the presence of the fluorenone moiety in FF triggers the AIEE
      property. 

PMID- 24108082
TI  - Life-threatening dermatologic adverse events in oncology.
AB  - The incidences of life-threatening toxicities such as Stevens-Johnson syndrome
      (SJS) and toxic epidermal necrolysis (TEN) are inconsistently reported. The
      potential association of anticancer agents with SJS or TEN has not been
      systematically investigated. We searched the literature (Ovid: 1950 to June 2013
      and PubMed: 1948 to June 2013) using terms for SJS/TEN and anticancer therapies.
      Primary case reports, case series, and clinical trials were included. In
      addition, MedWatch, the Food and Drug Administration Adverse Event Reporting
      System (FAERS), was searched (1968 to August 2012) for SJS/TEN reports associated
      with anticancer therapies. Proportional reporting ratios (PRR>2, N>3), empirical
      Bayes geometric mean (EBGM>2, N>3), and lower 95% confidence interval
      (EBGM0.05>2) were used as thresholds to constitute a signal of association
      between SJS/TEN and anticancer drugs. There were 46 SJS and 37 TEN cases
      associated with 18 and 22 anticancer drugs in the literature, respectively. Among
      cases in the FAERS, significant signals were associated with SJS for bendamustine
      and with TEN for bendamustine, busulfan, chlorambucil, fludarabine, lomustine,
      and procarbazine. Several drugs reported in the published literature to be
      associated with SJS/TEN were not found to have significant signals in FAERS.
      Proactive pharmacovigilance to detect and define safety signals serves to aid
      oncology practitioners in the recognition of possible, yet uncommon, serious,
      and/or life-threatening skin reactions. 

PMID- 24108085
TI  - Comment on 'Treatment of intractable anorexia nervosa with inactivation of the
      nucleus accumbens using stereotactic surgery'.

PMID- 24108086
TI  - UV, visible and near-infrared lights induced NOx destruction activity of (Yb,Er)
      NaYF4/C-TiO2 composite.
AB  - Titanium dioxide (TiO2) is a well-known photocatalyst for environmental cleaning
      and energy conversion. However, it can only be excited by ultraviolet light for
      photocatalysis due to its wide band gap (3.2 eV). In this paper, we present a
      novel (Yb,Er)-NaYF4/C-TiO2 composite which can be perfectly induced not only by
      ultraviolet light but also weak visible and near infrared lights, owing to the
      increased carbon doping contents and optimal energy transfer between up
      conversion phosphor and C doped TiO2 compared with that of solely C-TiO2.
      Consequently, the (Yb,Er)-NaYF4/C-TiO2 composite can present the outstanding
      continuous NOx gas destruction ability under the irradiation of ultraviolet, weak
      visible and infrared lights much superior to pure C-TiO2, P25 titania and even
      that of (Yb,Er)-NaYF4/N-TiO2 composite, due to the nice synergetic effect of
      (Yb,Er)-NaYF4 and C-TiO2, indicating a promising potential in the photocatalyst
      application with high efficiency of ultraviolet, visible and infrared lights
      induced photocatalysis simultaneously.

PMID- 24108087
TI  - Radical coupling for directed C-C/C-S bond formation in the reaction of
      Cp*IrS2C2B10H10 with 1-azido-3-nitrobenzene.
AB  - Reactions of half-sandwich complex Cp*IrS2C2B10H10 (1) with 1-azido-3
      nitrobenzene (3-NO2C6H4N3, L) upon heating or under light led to new complexes 2
      6. Complexes 2 and 3 contain a five-membered cyclometalated ligand arising from
      C(sp(2))-H activation of the azide ligand L. Complex 4 is a 16 electron species
      containing a new-generated C-C bond between the azide ligand L and the Cp* unit
      where C(sp(3))-H activation of the methyl unit occurred. Complexes 5 and 6
      contain two types of the ligand which appear in complexes 2, 3 and 4. Further
      reactions of complexes 5 and 6 with L under more harsh conditions gave rise to
      the nucleophilic addition products 7 and 8, where ring expansion of the azide
      ligand at the imido site of complexes 5 and 6 happened. Complexes 2-8 were
      characterized by NMR, MS, IR, and elemental analysis, and X-ray structural
      analyses were performed for complexes 2-4 and 6-8. The radical mechanisms for the
      formation of complexes 2-6 were proposed on the basis of capture experiments by
      EPR and ESI-MS. And the formation mechanism of complexes 7 and 8 was also
      suggested.

PMID- 24108088
TI  - Attitudes and preferences of young women with low and high fear of childbirth.
AB  - We examined constructions of labor and birth for 461 Canadian women who attended
      the University of British Columbia (Canada) and participated in an online survey
      about pregnancy and birth, using a combination of Likert items and open-ended
      questions. We performed a content analysis of women's open-ended responses about
      their feelings toward birth and analyzed comments of women with high and low fear
      of childbirth separately. Students with high fear of birth described childbirth
      as a frightening and painful ordeal and viewed obstetric interventions as a means
      to make labor and birth more manageable. Students with low fear constructed birth
      as a natural event and regarded interventions more critically. Students in both
      groups supported women's autonomous maternity care decisions. Our findings
      contribute to care providers' and educators' knowledge about preferences and
      fears expressed by the next generation of maternity care consumers and potential
      strategies to reduce their fear of childbirth. 

PMID- 24108089
TI  - Exploring the social and community context of African American adolescents' HIV
      vulnerability.
AB  - There is an increasing call for HIV prevention programs that target social
      determinants of HIV. The purpose of this study was to examine the experiences and
      perceptions of 12 African American adolescents to identify important social and
      community targets for HIV prevention. We used photovoice methodology to engage
      adolescents in a critical analysis of their experiences to arrive at a deeper
      understanding of the social determinants of HIV and determine specific action
      steps to reduce HIV risk. Analyses revealed a variety of social and environmental
      factors that affect the lives of African American adolescents by creating
      conditions that put them at greater risk for HIV. Study findings support
      mobilizing community action through raising awareness and advocating for
      increased neighborhood resources and institutional support. We conclude with
      research and practice implications for community-relevant HIV prevention among
      African American youth. 

PMID- 24108090
TI  - Assimilation and health service utilization of Korean immigrant women.
AB  - In this case study, I present descriptive findings with regard to immigrant
      incorporation and health service utilization. Using focus groups and survey of
      Korean immigrant women in Wisconsin, I examine whether the ways in which they
      adapt to the U.S. society is relevant to their health services utilization and
      the alternatives they seek when available health services are less than
      satisfactory. The findings suggest that adherence to Korean identity appears to
      be associated with health service utilization. This is evident in the immigrants'
      evaluation of the U.S. health services as compared to those of Korea, and the
      consideration given by these immigrants to seeking health services in Korea
      instead of the United States. Such concerns on the part of these immigrants have
      important implications for health researchers, as they highlight the significance
      of immigrants' transnational experiences and their sense of personal agency in
      the use of health care. 

PMID- 24108091
TI  - A single-molecule long-read survey of the human transcriptome.
AB  - Global RNA studies have become central to understanding biological processes, but
      methods such as microarrays and short-read sequencing are unable to describe an
      entire RNA molecule from 5' to 3' end. Here we use single-molecule long-read
      sequencing technology from Pacific Biosciences to sequence the polyadenylated RNA
      complement of a pooled set of 20 human organs and tissues without the need for
      fragmentation or amplification. We show that full-length RNA molecules of up to
      1.5 kb can readily be monitored with little sequence loss at the 5' ends. For
      longer RNA molecules more 5' nucleotides are missing, but complete intron
      structures are often preserved. In total, we identify ~14,000 spliced GENCODE
      genes. High-confidence mappings are consistent with GENCODE annotations, but >10%
      of the alignments represent intron structures that were not previously annotated.
      As a group, transcripts mapping to unannotated regions have features of long,
      noncoding RNAs. Our results show the feasibility of deep sequencing full-length
      RNA from complex eukaryotic transcriptomes on a single-molecule level. 

PMID- 24108092
TI  - Targeted DNA demethylation and activation of endogenous genes using programmable
      TALE-TET1 fusion proteins.
AB  - Genome-wide studies have defined cell type-specific patterns of DNA methylation
      that are important for regulating gene expression in both normal development and
      disease. However, determining the functional significance of specific methylation
      events remains challenging, owing to the lack of methods for removing such
      modifications in a targeted manner. Here we describe an approach for efficient
      targeted demethylation of specific CpGs in human cells using fusions of
      engineered transcription activator-like effector (TALE) repeat arrays and the
      TET1 hydroxylase catalytic domain. Using these TALE-TET1 fusions, we demonstrate
      that modification of critical methylated promoter CpG positions can lead to
      substantial increases in the expression of endogenous human genes. Our results
      delineate a strategy for understanding the functional significance of specific
      CpG methylation marks in the context of endogenous gene loci and validate
      programmable DNA demethylation reagents with potential utility for research and
      therapeutic applications. 

PMID- 24108094
TI  - Synthesis of oseltamivir and tamiphosphor from N-acetyl-D-glucosamine.
AB  - Using N-acetyl-D-glucosamine as a starting material, the anti-influenza drugs
      oseltamivir and tamiphosphor were synthesized via a pivotal intermediate of
      aldehyde 8. An intramolecular Horner-Wadsworth-Emmons reaction was utilized to
      construct the highly functionalized cyclohexene ring. The existing N-acetyl group
      was transformed into an azido group for the subsequent aziridination, followed by
      implantation of a 3-pentoxy group of the desired stereochemistry.

PMID- 24108093
TI  - Spatially isotropic four-dimensional imaging with dual-view plane illumination
      microscopy.
AB  - Optimal four-dimensional imaging requires high spatial resolution in all
      dimensions, high speed and minimal photobleaching and damage. We developed a dual
      view, plane illumination microscope with improved spatiotemporal resolution by
      switching illumination and detection between two perpendicular objectives in an
      alternating duty cycle. Computationally fusing the resulting volumetric views
      provides an isotropic resolution of 330 nm. As the sample is stationary and only
      two views are required, we achieve an imaging speed of 200 images/s (i.e., 0.5 s
      for a 50-plane volume). Unlike spinning-disk confocal or Bessel beam methods,
      which illuminate the sample outside the focal plane, we maintain high
      spatiotemporal resolution over hundreds of volumes with negligible
      photobleaching. To illustrate the ability of our method to study biological
      systems that require high-speed volumetric visualization and/or low
      photobleaching, we describe microtubule tracking in live cells, nuclear imaging
      over 14 h during nematode embryogenesis and imaging of neural wiring during
      Caenorhabditis elegans brain development over 5 h. 

PMID- 24108096
TI  - Tumour microenvironment: Teaching old macrophages new tricks.

PMID- 24108098
TI  - Prostate cancer: understanding why.

PMID- 24108099
TI  - Neuropsychological outcome after deep brain stimulation in the ventral
      capsule/ventral striatum for highly refractory obsessive-compulsive disorder or
      major depression.
AB  - BACKGROUND: Deep brain stimulation (DBS) has shown promise as a treatment for
      severe, highly treatment-refractory obsessive-compulsive disorder (OCD) or major
      depressive disorder (MDD). We describe the neuropsychological outcome in 21
      patients (10 OCD and 11 MDD) who received DBS in the anterior limb of the
      internal capsule/ventral striatum (VC/VS). METHODS: All patients completed a
      preoperative and postoperative neuropsychological battery. Average duration of
      DBS stimulation was 8.91 months (SD = 4.63) at the time of follow-up testing.
      Data were analyzed using practice-effect-corrected change scores. RESULTS: No
      significant cognitive declines were seen. There were significant improvements in
      prose passage recall after chronic DBS. The cognitive improvements were not
      related to change in severity of OCD, depression or global impairment.
      CONCLUSIONS: This preliminary study suggests that VC/VS DBS does not result in
      cognitive declines. The observations that verbal memory improved are consistent
      with current theories on the role of the VS in the memory, but require
      replication in larger studies.

PMID- 24108097
TI  - A central role for vesicle trafficking in epithelial neoplasia: intracellular
      highways to carcinogenesis.
AB  - Epithelial cell carcinogenesis involves the loss of cell polarity, alteration of
      polarized protein presentation, dynamic cell morphology changes, increased
      proliferation, and increased cell motility and invasion. Membrane vesicle
      trafficking underlies all of these processes. Specific membrane trafficking
      regulators, including RAB small GTPases, through the coordinated dynamics of
      intracellular trafficking along cytoskeletal pathways, determine the cell surface
      presentation of proteins and the overall function of both differentiated and
      neoplastic cells. Although mutations in vesicle trafficking proteins may not be
      direct drivers of transformation, components of the machinery of vesicle movement
      have crucial roles in the phenotypes of neoplastic cells. Therefore, the
      regulators of membrane vesicle trafficking decisions are essential mediators of
      the full range of cell physiologies that drive cancer cell biology, including
      initial loss of cell polarity, invasion and metastasis. Targeting of these
      fundamental intracellular processes may permit the manipulation of cancer cell
      behaviour. 

PMID- 24108100
TI  - Patient selection for day case-eligible surgery: identifying those at high risk
      for major complications.
AB  - BACKGROUND: Due to economic pressures and improvements in perioperative care,
      outpatient surgical procedures have become commonplace. However, risk factors for
      outpatient surgical morbidity and mortality remain unclear. There are no
      multicenter clinical data guiding patient selection for outpatient surgery. The
      authors hypothesize that specific risk factors increase the likelihood of day
      case-eligible surgical morbidity or mortality. METHODS: The authors analyzed
      adults undergoing common day case-eligible surgical procedures by using the
      American College of Surgeons' National Surgical Quality Improvement Program
      database from 2005 to 2010. Common day case-eligible surgical procedures were
      identified as the most common outpatient surgical Current Procedural Terminology
      codes provided by Blue Cross Blue Shield of Michigan and Medicare publications.
      Study variables included anthropometric data and relevant medical comorbidities.
      The primary outcome was morbidity or mortality within 72 h. Intraoperative
      complications included adverse cardiovascular events; postoperative complications
      included surgical, anesthetic, and medical adverse events. RESULTS: Of 244,397
      surgeries studied, 232 (0.1%) experienced early perioperative morbidity or
      mortality. Seven independent risk factors were identified while controlling for
      surgical complexity: overweight body mass index, obese body mass index, chronic
      obstructive pulmonary disease, history of transient ischemic attack/stroke,
      hypertension, previous cardiac surgical intervention, and prolonged operative
      time. CONCLUSIONS: The demonstrated low rate of perioperative morbidity and
      mortality confirms the safety of current day case-eligible surgeries. The authors
      obtained the first prospectively collected data identifying risk factors for
      morbidity and mortality with day case-eligible surgery. The results of the study
      provide new data to advance patient-selection processes for outpatient surgery.

PMID- 24108101
TI  - Electronic spectroscopy of transient species in solid neon: the indene-motif
      polycyclic hydrocarbon cation family C9Hy(+) (y = 7-9) and their neutrals.
AB  - In this Perspective the development and application of a mass-selective matrix
      isolation approach, employed with success over the last two decades in the
      spectroscopic characterization of numerous ions and neutral reactive species, is
      illustrated with original data for hydrocarbon cations and neutrals with a six-
      and a five-membered carbon ring fused. The setup allows for the electronic and
      vibrational assessment of these isolated molecules and ions in the inert neon
      environment. The transient species of interest are chosen due to their
      astrophysical relevance, and the role they play in flames, plasmas, combustion,
      organic reactions and atmospheric chemistry. Electronic absorption and
      fluorescence spectra of indene-related polycyclic aromatic hydrocarbon
      derivatives, C9Hy(+) (y = 7-9) cations, are presented. The ions were produced in
      a discharge source and investigated by means of absorption and emission
      spectroscopies after selectively trapping them in 6 K neon matrices.
      Photoconversion between the two C9H8(+) indenylium isomers and, upon irradiation,
      H2 loss from C9H9(+) were observed. Corresponding neutral species C9Hy are
      identified by photobleaching the matrices containing the cations. 

PMID- 24108102
TI  - Comment on 'no association of primary Sjogren's syndrome with Fcgamma receptor
      gene variants'.

PMID- 24108103
TI  - Reply to 'comment on no association of primary Sjogren's syndrome with Fcgamma
      receptor gene variants'.

PMID- 24108104
TI  - Widespread spinal cord transduction by intrathecal injection of rAAV delivers
      efficacious RNAi therapy for amyotrophic lateral sclerosis.
AB  - Amyotrophic lateral sclerosis (ALS) causes motor neuron degeneration and
      paralysis. No treatment can significantly slow or arrest the disease progression.
      Mutations in the SOD1 gene cause a subset of familial ALS by a gain of toxicity.
      In principle, these cases could be treated with RNAi that destroys the mutant
      mRNA, thereby abolishing the toxic protein. However, no system is available to
      efficiently deliver the RNAi therapy. Recombinant adenoassociated virus (rAAV) is
      a promising vehicle due to its long-lasting gene expression and low toxicity.
      However, ALS afflicts broad areas of the central nervous system (CNS). A lack of
      practical means to spread rAAV broadly has hindered its application in treatment
      of ALS. To overcome this barrier, we injected several rAAV serotypes into the
      cerebrospinal fluid. We found that some rAAV serotypes such as rAAVrh10 and rAAV9
      transduced cells throughout the length of the spinal cord following a single
      intrathecal injection and in the broad forebrain following a single injection
      into the third ventricle. Furthermore, a single intrathecal injection of rAAVrh10
      robustly transduced motor neurons throughout the spinal cord in a non-human
      primate. These results suggested a therapeutic potential of this vector for ALS.
      To test this, we injected a rAAVrh10 vector that expressed an artificial miRNA
      targeting SOD1 into the SOD1G93A mice. This treatment knocked down the mutant
      SOD1 expression and slowed the disease progression. Our results demonstrate the
      potential of rAAVs for delivering gene therapy to treat ALS and other diseases
      that afflict broad areas of the CNS. 

PMID- 24108105
TI  - Deregulation of Fragile X-related protein 1 by the lipodystrophic lamin A p.R482W
      mutation elicits a myogenic gene expression program in preadipocytes.
AB  - The nuclear lamina is implicated in the regulation of various nuclear functions.
      Several laminopathy-causing mutations in the LMNA gene, notably the p.R482W
      substitution linked to familial partial lipodystrophy type 2 (FPLD2), are
      clustered in the immunoglobulin fold of lamin A. We report a functional
      association between lamin A and fragile X-related protein 1 (FXR1P), a protein of
      the fragile X-related family involved in fragile X syndrome. Searching for
      proteins differentially interacting with the immunoglobulin fold of wild-type and
      R482W mutant lamin A, we identify FXR1P as a novel component of the lamin A
      protein network. The p.R482W mutation abrogates interaction of FXR1P with lamin
      A. Fibroblasts from FPLD2 patients display elevated levels of FXR1P and
      delocalized FXR1P. In human adipocyte progenitors, deregulation of lamin A
      expression leads to FXR1P up-regulation, impairment of adipogenic differentiation
      and induction of myogenin expression. FXR1P overexpression also stimulates a
      myogenic gene expression program in these cells. Our results demonstrate a cross
      talk between proteins hitherto implicated in two distinct mesodermal pathologies.
      We propose a model where the FPLD2 lamin A p.R482W mutation elicits, through up
      regulation of FXR1P, a remodeling of an adipogenic differentiation program into a
      myogenic program. 

PMID- 24108106
TI  - Connexin defects underlie arrhythmogenic right ventricular cardiomyopathy in a
      novel mouse model.
AB  - Arrhythmogenic right ventricular cardiomyopathy (ARVC) termed a 'disease of the
      desmosome' is an inherited cardiomyopathy that recently underwent
      reclassification owing to the identification of left-dominant and biventricular
      disease forms. Homozygous loss-of-function mutations in the desmosomal component,
      desmoplakin, are found in patients exhibiting a biventricular form of ARVC;
      however, no models recapitulate the postnatal hallmarks of the disease as seen in
      these patients. To gain insights into the homozygous loss-of-function effects of
      desmoplakin in the heart, we generated cardiomyocyte-specific desmoplakin
      deficient mice (DSP-cKO) using ventricular myosin light chain-2-Cre mice.
      Homozygous DSP-cKO mice are viable but display early ultrastructural defects in
      desmosomal integrity leading to a cardiomyopathy reminiscent of a biventricular
      form of ARVC, which includes cell death and fibro-fatty replacement within the
      ventricle leading to biventricular dysfunction, failure and premature death. DSP
      cKO mice also exhibited ventricular arrhythmias that are exacerbated with
      exercise and catecholamine stimulation. Furthermore, DSP-cKO hearts exhibited
      right ventricular conduction defects associated with loss of connexin 40
      expression and electrical wavefront propagation defects associated with loss of
      connexin 43 expression. Dose-dependent assessment of the effects of loss of
      desmoplakin in neonatal ventricular cardiomyocytes revealed primary loss of
      connexin 43 levels, phosphorylation and function independent of the molecular
      dissociation of the mechanical junction complex and fibro-fatty manifestation
      associated with ARVC, suggesting a role for desmoplakin as a primary stabilizer
      of connexin integrity. In summary, we provide evidence for a novel mouse model,
      which is reminiscent of the postnatal onset of ARVC while highlighting mechanisms
      underlying a biventricular form of human ARVC. 

PMID- 24108107
TI  - Genome-wide alteration of 5-hydroxymethylcytosine in a mouse model of fragile X
      associated tremor/ataxia syndrome.
AB  - Fragile X-associated tremor/ataxia syndrome (FXTAS) is a late-onset
      neurodegenerative disorder in which patients carry premutation alleles of 55-200
      CGG repeats in the FMR1 gene. To date, whether alterations in epigenetic
      regulation modulate FXTAS has gone unexplored. 5-Hydroxymethylcytosine (5hmC)
      converted from 5-methylcytosine (5mC) by the ten-eleven translocation (TET)
      family of proteins has been found recently to play key roles in neuronal
      functions. Here, we undertook genome-wide profiling of cerebellar 5hmC in a FXTAS
      mouse model (rCGG mice) and found that rCGG mice at 16 weeks showed overall
      reduced 5hmC levels genome-wide compared with age-matched wild-type littermates.
      However, we also observed gain-of-5hmC regions in repetitive elements, as well as
      in cerebellum-specific enhancers, but not in general enhancers. Genomic
      annotation and motif prediction of wild-type- and rCGG-specific differential 5
      hydroxymethylated regions (DhMRs) revealed their high correlation with genes and
      transcription factors that are important in neuronal developmental and functional
      pathways. DhMR-associated genes partially overlapped with genes that were
      differentially associated with ribosomes in CGG mice identified by bacTRAP
      ribosomal profiling. Taken together, our data strongly indicate a functional role
      for 5hmC-mediated epigenetic modulation in the etiology of FXTAS, possibly
      through the regulation of transcription. 

PMID- 24108108
TI  - AIPL1, A protein linked to blindness, is essential for the stability of enzymes
      mediating cGMP metabolism in cone photoreceptor cells.
AB  - Defects in the photoreceptor-specific gene encoding aryl hydrocarbon receptor
      interacting protein like-1 (AIPL1) are linked to blinding diseases, including
      Leber congenital amaurosis (LCA) and cone dystrophy. While it is apparent that
      AIPL1 is needed for rod and cone function, the role of AIPL1 in cones is not
      clear. In this study, using an all-cone animal model lacking Aipl1, we show a
      light-independent degeneration of M- and S-opsin containing cones that proceeds
      in a ventral-to-dorsal gradient. Aipl1 is needed for stability, assembly and
      membrane association of cone PDE6, an enzyme crucial for photoreceptor function
      and survival. Furthermore, RetGC1, a protein linked to LCA that is needed for
      cGMP synthesis, was dramatically reduced in cones lacking Aipl1. A defect in
      RetGC1 is supported by our finding that cones lacking Aipl1 exhibited reduced
      levels of cGMP. These findings are in contrast to the role of Aipl1 in rods,
      where destabilization of rod PDE6 results in an increase in cGMP levels, which
      drives rapid rod degeneration. Our results illustrate mechanistic differences
      behind the death of rods and cones in retinal degenerative disease caused by
      deficiencies in AIPL1. 

PMID- 24108110
TI  - Are endoscopic endpoints reliable in therapeutic trials of ulcerative colitis?
AB  - BACKGROUND: The consistency of endoscopic and histologic findings in patients
      with ulcerative colitis (UC) has not been elucidated. Choice of assessment may
      affect study outcomes. METHODS: Post hoc analyses were performed using data from
      2 randomized, controlled multicenter trials: (1) SAG-26, mesalazine granules for
      induction of remission in UC (n = 380), and (2) SAG-27, mesalazine granules for
      maintenance of UC remission (n = 647). Assessments included Clinical Activity
      Index, Endoscopic Index, modified Disease Activity Index, and Histology Index.
      RESULTS: In SAG-26, 52 of 380 patients (13.7%) with clinically (Clinical Activity
      Index >4) and endoscopically (Endoscopic Index >=4) active UC showed no
      histological signs of active inflammation (Histology Index <=1) at baseline.
      Among endoscopically and histologically active patients, 246 of 327 (75.2%)
      reached clinical remission versus 48 of 52 patients (92.3%) with active endoscopy
      but no inflammation on histology (difference, 17.1%; P = 0.006). The difference
      in the proportion of patients achieving clinical remission according to endoscopy
      and histology in clinically inactive (Clinical Activity Index <=4) patients was
      30.8% in SAG-26 (at the study end) and 28.1% in SAG-27 (at baseline). In SAG-27,
      clinical relapse occurred in 21.2% of patients with endoscopic and histologic
      remission at baseline and 27.1% of patients with some histological inflammation
      at baseline (P = 0.111). Using the modified Disease Activity Index <=1 (mucosal
      healing) instead of the Endoscopic Index score, the difference was similar (21.2%
      versus 28.0%, P = 0.073). CONCLUSIONS: Endoscopic and histologic assessments
      differ in both active and inactive UC. Overdiagnosis of inflammation using
      endoscopy versus histology can significantly affect outcomes, at least in studies
      using induction of clinical remission as an endpoint. The assessment criteria for
      trials in UC should be reconsidered.

PMID- 24108109
TI  - The dual role of filamin A in cancer: can't live with (too much of) it, can't
      live without it.
AB  - Filamin A (FlnA) has been associated with actin as cytoskeleton regulator.
      Recently its role in the cell has come under scrutiny for FlnA's involvement in
      cancer development. FlnA was originally revealed as a cancer-promoting protein,
      involved in invasion and metastasis. However, recent studies have also found that
      under certain conditions, it prevented tumor formation or progression, confusing
      the precise function of FlnA in cancer development. Here, we try to decipher the
      role of FlnA in cancer and the implications for its dual role. We propose that
      differences in subcellular localization of FlnA dictate its role in cancer
      development. In the cytoplasm, FlnA functions in various growth signaling
      pathways, such as vascular endothelial growth factor, in addition to being
      involved in cell migration and adhesion pathways, such as R-Ras and integrin
      signaling. Involvement in these pathways and various others has shown a
      correlation between high cytoplasmic FlnA levels and invasive cancers. However,
      an active cleaved form of FlnA can localize to the nucleus rather than the
      cytoplasm and its interaction with transcription factors has been linked to a
      decrease in invasiveness of cancers. Therefore, overexpression of FlnA has a
      tumor-promoting effect, only when it is localized to the cytoplasm, whereas if
      FlnA undergoes proteolysis and the resulting C-terminal fragment localizes to the
      nucleus, it acts to suppress tumor growth and inhibit metastasis. Development of
      drugs to target FlnA and cause cleavage and subsequent localization to the
      nucleus could be a new and potent field of research in treating cancer.

PMID- 24108111
TI  - Gene expression profiles of ileal inflammatory bowel disease correlate with
      disease phenotype and advance understanding of its immunopathogenesis.
AB  - BACKGROUND: Pouchitis may develop in patients with ulcerative colitis undergoing
      pouch surgery. We aimed to evaluate the de novo inflammation developing in the
      ileal pouch, hypothesizing that it may be similar to ileitis in Crohn's disease
      (CD). METHODS: Patients with ulcerative colitis pouch were prospectively
      recruited, stratified according to disease behavior into normal pouch, chronic
      pouchitis, and Crohn's-like disease of the pouch groups, and compared with
      controls. Gene expression analysis was performed using microarrays, validated by
      real-time polymerase chain reaction. Gene ontology and clustering were evaluated
      using bioinformatic tools. RESULTS: Sixty-six subjects were recruited. Although
      in ulcerative colitis ileum there were no significant gene expression
      alterations, patients with normal pouch had 168 significant alterations (fold
      change >= 2, corrected P <= 0.05). In chronic pouchitis and Crohn's-like disease
      of the pouch, 490 and 1152 alterations were detected, respectively. High degree
      of overlap in gene expression alterations between the pouch subgroups was
      demonstrated. The magnitude of change correlated with pouch disease behavior.
      Gene expression profiles were more reflective of disease behavior compared with
      inflammatory indices. CD ileitis had 358 alterations, with a 90% overlap with
      pouchitis. Gene ontology analyses revealed multiple biological processes
      associated with pouch inflammation, including response to chemical stimulus,
      small molecule metabolic and immune system processes, and specific infection
      related pathways such as Staphylococcus aureus, leishmaniasis, and tuberculosis.
      CONCLUSIONS: Gene alterations in pouch inflammation and CD overlap, suggesting
      that inflammatory bowel diseases is a spectrum, rather than distinct diseases.
      Pouchitis may serve as a model of CD. The novel pathways associated with
      inflammatory bowel diseases may decipher pathophysiology and suggest targets for
      intervention.

PMID- 24108112
TI  - Reduced plasma fibrin clot permeability and susceptibility to lysis in patients
      with inflammatory bowel disease: a novel prothrombotic mechanism.
AB  - BACKGROUND: Inflammatory bowel disease (IBD) is associated with an increased risk
      of thromboembolism. Its mechanism is still unclear. Altered fibrin clot
      properties have been reported in patients with thromboembolism and those with
      chronic inflammatory states. We investigated whether fibrin characteristics are
      abnormal in IBD. METHODS: Ex vivo plasma fibrin clot permeability (Ks),
      compaction, turbidity, and efficiency of fibrinolysis were assessed in 85
      consecutive patients with IBD, including 47 with ulcerative colitis (UC) and 38
      with Crohn's disease (CD), all with no history of thromboembolism. Forty-eight
      patients matched for age and sex served as controls. RESULTS: Compared with
      controls, patients with UC and CD had 29.5% and 35.7% lower Ks associated with
      13.8% and 23.1% lower compaction, respectively (all P < 0.001). Patients with UC
      and CD had higher maximum clot absorbance (+8.9%, P = 0.008, and +15.2%, P <
      0.0001, respectively), higher maximum D-dimer released from clots (D-D(max),
      +27.0%, P = 0.01, and +28.7%, P < 0.0001, respectively), and prolonged clot lysis
      time (+19.0%, P < 0.0001, and +25.5%, P < 0.0001, respectively). Lag phase was
      similar in both group of patients. D-D(max) was the only parameter that differed
      between patients in the UC and CD groups, being higher in CD (P = 0.04). The
      multiple linear regression model showed that in patients with UC, but not with
      CD, Ks, compaction, lysis time, and D-D(max) were all independently associated
      with disease activity. In patients with CD, Ks and lysis time were independently
      predicted by fibrinogen and C-reactive protein. CONCLUSIONS: Both UC and CD are
      characterized by formation of dense fibrin networks relatively resistant to
      lysis. Prothrombotic clot phenotype might represent a novel mechanism increasing
      thrombotic risk in IBD.

PMID- 24108113
TI  - Impact of JC virus antibody testing in patients with Crohn's disease with loss of
      response to infliximab: a Markov model.
AB  - BACKGROUND: The optimal treatment strategy for patients with Crohn's disease who
      have loss of response to the anti-tumor necrosis factor alpha medication
      infliximab is uncertain. Natalizumab has an alternative mechanism of action, but
      its use has been limited by the risk of progressive multifocal
      leukoencephalopathy. In this study, we performed a decision analysis assessing
      the impact of JC virus (JCV) antibody testing and natalizumab utilization for
      loss of response to infliximab. METHODS: We constructed a Markov model to assess
      the difference between unscreened natalizumab use (option 1), JCV antibody
      testing with natalizumab when appropriate (option 2), and second anti-tumor
      necrosis factor alpha use (option 3). The base case was a 35-year-old man with
      severe Crohn's disease with loss of response to infliximab. The time horizon was
      3 years. Results are reported in quality-adjusted life years (QALYs).
      Deterministic and probabilistic analyses were conducted. Markov analysis using a
      cohort of 5000 individuals was performed. The impact of JCV antibody status on
      outcomes in this model was assessed. RESULTS: Option 2 was the preferred strategy
      (2.0880 QALYs), followed by option 1 (2.0875 QALYs) and option 3 (2.0808 QALYs).
      Patients in option 2 required fewer surgeries compared with option 3. Previous
      JCV infection was associated with reduced QALYs with all options that allowed for
      natalizumab use. CONCLUSIONS: JCV antibody testing and subsequent treatment
      selection yield improved outcomes over natalizumab without testing or using only
      a second anti-tumor necrosis factor alpha in all patients.

PMID- 24108114
TI  - Profermin is efficacious in patients with active ulcerative colitis--a randomized
      controlled trial.
AB  - BACKGROUND: Profermin is developed for the dietary management of ulcerative
      colitis (UC). It consists of water, fermented oats, barley malt, lecithin, and
      Lactobacillus plantarum 299v. The aim of this study was to assess the clinical
      efficacy of Profermin. METHODS: Seventy-four patients with a mild-to-moderate
      flare-up of UC (defined as Simple Clinical Colitis Activity Index [SCCAI] score
      >=5 and <=11) were randomly assigned to Profermin (n = 32) or Fresubin (n = 41).
      The primary endpoint was to assess whether addition of Profermin in UC could
      significantly reduce SCCAI in comparison with Fresubin. RESULTS: In the run-in
      period, the mean SCCAI was 7.2 +/- 1.50 in the Profermin group and 7.6 +/- 1.47
      in the Fresubin group (not significant). After 8 weeks of treatment, the mean
      reduction of SCCAI score was higher in the Profermin group (mean difference: 
      1.77 SCCAI, 95% confidence interval -2.97 to -0.55; P < 0.005), in intention-to
      treat analyses. Remission defined as SCCAI <=2.5 was achieved in 10 of 32 (31%)
      in the Profermin group and in 6 of 41 (15%) in the Fresubin group (P = 0.048).
      The decrease in SCCAI scores of >=50% was higher in the Profermin group 17 of 32
      (53%) versus 11 of 41 (27%) (P = 0.04). The risk of dropping out due to treatment
      failure/lack of effect was higher in the Fresubin group (42% versus 13%, P =
      0.02). CONCLUSIONS: Supplementation with Profermin is safe, well tolerated,
      palatable, and able to reduce SCCAI scores at a statistically and clinically
      significant level in patients with mild-to-moderate UC with a flare-up.

PMID- 24108115
TI  - Tumor necrosis factor-neuropeptide Y cross talk regulates inflammation,
      epithelial barrier functions, and colonic motility.
AB  - BACKGROUND: Neuro-immune interactions play a significant role in regulating the
      severity of inflammation. Our previous work demonstrated that neuropeptide Y
      (NPY) is upregulated in the enteric nervous system during murine colitis and that
      NPY knockout mice exhibit reduced inflammation. Here, we investigated if NPY
      expression during inflammation is induced by tumor necrosis factor (TNF), the
      main proinflammatory cytokine. METHODS: Using primary enteric neurons and colon
      explant cultures from wild type and NPY knockout (NPY(-/-)) mice, we determined
      if NPY knockdown modulates TNF release and epithelial permeability. Further, we
      assessed if NPY expression is inducible by TNF in enteric neuronal cells and
      mouse model of experimental colitis, using the TNF inhibitors-etanercept (blocks
      transmembrane and soluble TNF) and XPro1595 (blocks soluble TNF only). RESULTS:
      We found that enteric neurons express TNF receptors (TNFR1 and R2). Primary
      enteric neurons from NPY(-/-) mice produced less TNF compared with wild type.
      Further, TNF activated NPY promoter in enteric neurons through phospho-c-Jun.
      NPY(-/-) mice had decreased intestinal permeability. In vitro, NPY increased
      epithelial permeability through phosphatidyl inositol-3-kinase (PI3-K)-induced
      pore-forming claudin-2. TNF inhibitors attenuated NPY expression in vitro and in
      vivo. TNF inhibitor-treated colitic mice exhibited reduced NPY expression and
      inflammation, reduced oxidative stress, enhanced neuronal survival, and improved
      colonic motility. XPro1595 had more protective effects on neuronal survival and
      motility compared with etanercept. CONCLUSIONS: We demonstrate a novel TNF-NPY
      cross talk that modulates inflammation, barrier functions, and colonic motility
      during inflammation. It is also suggested that selective blocking of soluble TNF
      may be a better therapeutic option than using anti-TNF antibodies.

PMID- 24108116
TI  - Extracorporeal membrane oxygenation versus counterpulsatile, pulsatile, and
      continuous left ventricular unloading for pediatric mechanical circulatory
      support.
AB  - OBJECTIVES: Despite progress with adult ventricular assist devices, limited
      options exist to support pediatric patients with life-threatening heart disease.
      Extracorporeal membrane oxygenation remains the clinical standard. To
      characterize (patho)physiologic responses to different modes of mechanical
      unloading of the failing pediatric heart, extracorporeal membrane oxygenation was
      compared to intra-aortic balloon pump, pulsatile-flow ventricular assist device,
      or continuous-flow ventricular assist device support in a pediatric heart failure
      model. DESIGN: Experimental. SETTING: Large animal laboratory operating room.
      SUBJECTS: Yorkshire piglets (n = 47; 11.7 +/- 2.6 kg). INTERVENTIONS: In piglets
      with coronary ligation-induced cardiac dysfunction, mechanical circulatory
      support devices were implanted and studied during maximum support. MEASUREMENTS
      AND MAIN RESULTS: Left ventricular, right ventricular, coronary, carotid,
      systemic arterial, and pulmonary arterial hemodynamics were measured with
      pressure and flow transducers. Myocardial oxygen consumption and total-body
      oxygen consumption were calculated from arterial, venous, and coronary sinus
      blood sampling. Blood flow was measured in 17 organs with microspheres. Paired
      Student t tests compared baseline and heart failure conditions. One-way repeated
      measures analysis of variance compared heart failure, device support mode(s), and
      extracorporeal membrane oxygenation. Statistically significant (p < 0.05)
      findings included 1) an improved left ventricular blood supply/demand ratio
      during pulsatile-flow ventricular assist device, continuous-flow ventricular
      assist device, and extracorporeal membrane oxygenation but not intra-aortic
      balloon pump support, 2) an improved global myocardial blood supply/demand ratio
      during pulsatile-flow ventricular assist device and continuous-flow ventricular
      assist device but not intra-aortic balloon pump or extracorporeal membrane
      oxygenation support, and 3) diminished pulsatility during extracorporeal membrane
      oxygenation and continuous-flow ventricular assist device but not intra-aortic
      balloon pump and pulsatile-flow ventricular assist device support. A profile of
      systems-based responses was established for each type of support. CONCLUSIONS:
      Each type of pediatric ventricular assist device provided hemodynamic support by
      unloading the heart with a different mechanism that created a unique profile of
      physiological changes. These data contribute novel, clinically relevant insight
      into pediatric mechanical circulatory support and establish an important resource
      for pediatric device development and patient selection.

PMID- 24108117
TI  - Functional outcomes in pediatric severe sepsis: further analysis of the
      researching severe sepsis and organ dysfunction in children: a global perspective
      trial.
AB  - OBJECTIVES: To evaluate risk factors for poor functional outcome in 28-day
      survivors after an episode of severe sepsis. DESIGN: Retrospective cohort study
      examining data from the Researching Severe Sepsis and Organ Dysfunction in
      Children: A Global Perspective trial (NCT00049764). SETTING: One hundred and four
      pediatric centers in 18 countries. SUBJECTS: Children with severe sepsis who
      required both vasoactive-inotropic infusions and mechanical ventilation and who
      survived to 28 days (n = 384). INTERVENTIONS: None. MEASUREMENTS AND MAIN
      RESULTS: Poor functional outcome was defined as a Pediatric Overall Performance
      Category score greater than or equal to 3 and an increase from baseline when
      measured 28 days after trial enrollment. Median Pediatric Overall Performance
      Category at enrollment was 1 (interquartile range, 1-2). Median Pediatric Overall
      Performance Category at 28 days was 2 (interquartile range, 1-4). Thirty-four
      percent of survivors had decline in their functional status at 28 days, and 18%
      were determined to have a "poor" functional outcome. Hispanic ethnicity was
      associated with poor functional outcome compared to the white referent group
      (risk ratio = 1.9; 95% CI: 1.0-3.0). Clinical factors associated with increased
      risk of poor outcome included CNS and intra-abdominal infection sources compared
      to the lung infection referent category (risk ratio = 3.3; 95% CI: 1.4-5.6 and
      2.4; 95% CI: 1.0-4.5, respectively); a history of recent trauma (risk ratio =
      3.9; 95% CI: 1.4-5.4); receipt of cardiopulmonary resuscitation prior to
      enrollment (risk ratio = 5.1; 95% CI: 2.9-5.7); and baseline Pediatric Risk of
      Mortality III score of 20-29 (risk ratio = 2.8; 95% CI: 1.2-5.2) and Pediatric
      Risk of Mortality III greater than or equal to 30 (risk ratio = 4.5; 95% CI: 1.6
      8.0) compared to the referent group with Pediatric Risk of Mortality III scores
      of 0-9. CONCLUSIONS: In this sample of 28-day survivors of pediatric severe
      sepsis diminished functional status was common. This analysis provides evidence
      that particular patient characteristics and aspects of an individual's clinical
      course are associated with poor functional outcome 28 days after onset of severe
      sepsis. These characteristics may provide opportunity for intervention in order
      to improve functional outcome in pediatric patients with severe sepsis. Decline
      in functional status 28 days after onset of severe sepsis is a frequent and
      potentially clinically meaningful event. Utilization of functional status as the
      primary outcome in future pediatric sepsis clinical trials should be considered.

PMID- 24108118
TI  - Extracorporeal membrane oxygenation for neonatal and pediatric respiratory
      failure: an evidence-based review of the past decade (2002-2012).
AB  - OBJECTIVE: To provide a comprehensive evidence-based review of extracorporeal
      membrane oxygenation for neonatal and pediatric respiratory failure. DATA SOURCE:
      A thorough computerized bibliographic search of the clinical literature regarding
      the use of extracorporeal membrane oxygenation in the neonatal and pediatric
      populations. STUDY SELECTION: Clinical trials published between January 1, 2002,
      and October 1, 2012, including "extracorporeal membrane oxygenation" or "ECMO"
      and limited to studies involving humans aged 0-18 years. Trials focused on
      extracorporeal membrane oxygenation for cardiac indications were excluded from
      this study, unless the study was evaluating ancillary therapies in conjunction
      with extracorporeal membrane oxygenation. DATA EXTRACTION: Studies were evaluated
      for inclusion based on reporting of patient outcomes and/or strategic
      considerations, such as cannulation strategies, timing of extracorporeal membrane
      oxygenation utilization, and ancillary therapies. DATA SYNTHESIS: Pertinent data
      are summarized, and the available data are objectively classified based on the
      value of the study design from which the data are obtained. CONCLUSIONS: Despite
      a large number of published extracorporeal membrane oxygenation studies, there
      remains a paucity of high-quality clinical trials. The available data support
      continued use of extracorporeal membrane oxygenation for respiratory failure
      refractory to conventional therapy for neonatal and pediatric patients without
      significant comorbidities. Further research is needed to better quantify the
      benefit of extracorporeal membrane oxygenation and the utility of many therapies
      commonly applied to extracorporeal membrane oxygenation patients.

PMID- 24108119
TI  - High-content analysis to leverage a robust phenotypic profiling approach to
      vascular modulation.
AB  - Phenotypic screening seeks to identify substances that modulate phenotypes in a
      desired manner with the aim of progressing first-in-class agents. Successful
      campaigns require physiological relevance, robust screening, and an ability to
      deconvolute perturbed pathways. High-content analysis (HCA) is increasingly used
      in cell biology and offers one approach to prosecution of phenotypic screens, but
      challenges exist in exploitation where data generated are high volume and
      complex. We combine development of an organotypic model with novel HCA tools to
      map phenotypic responses to pharmacological perturbations. We describe
      implementation for angiogenesis, a process that has long been a focus for
      therapeutic intervention but has lacked robust models that recapitulate more
      completely mechanisms involved. The study used human primary endothelial cells in
      co-culture with stromal fibroblasts to model multiple aspects of angiogenic
      signaling: cell interactions, proliferation, migration, and differentiation.
      Multiple quantitative descriptors were derived from automated microscopy using
      custom-designed algorithms. Data were extracted using a bespoke informatics
      platform that integrates processing, statistics, and feature display into a
      streamlined workflow for building and interrogating fingerprints. Ninety
      compounds were characterized, defining mode of action by phenotype. Our approach
      for assessing phenotypic outcomes in complex assay models is robust and capable
      of supporting a range of phenotypic screens at scale. 

PMID- 24108120
TI  - High-throughput fluorescence anisotropy screen for inhibitors of the oncogenic
      mRNA binding protein, IMP-1.
AB  - Cancer cell proliferation is regulated by oncogenes, such as c-Myc. An
      alternative approach to directly targeting individual oncogenes is to target IMP
      1, an oncofetal protein that binds to and stabilizes messenger RNAs (mRNAs),
      leading to elevated expression of c-Myc and other oncogenes. Expression of IMP-1
      is tightly correlated with a poor prognosis and reduced survival in ovarian,
      lung, and colon cancer. Small-molecule inhibitors of IMP-1 have not been
      reported. We established a fluorescence anisotropy/polarization microplate assay
      (FAMA) for analyzing binding of IMP-1 to a fluorescein-labeled 93 nucleotide c
      Myc mRNA target (flMyc), developed the assay as a highly robust (Z' factor =
      0.60) FAMA-based high-throughput screen for inhibitors of binding of IMP-1 to
      flMyc, and carried out a successful pilot screen of 17,600 small molecules. Our
      studies support rapidly filtering out toxic nonspecific inhibitors using an early
      cell-based assay in control cells lacking the target protein. The physiologic
      importance of verified hits from the in vitro high-throughput screen was
      demonstrated by identification of the first small-molecule IMP-1 inhibitor, a
      lead compound that selectively inhibits proliferation of IMP-1-positive cancer
      cells with very little or no effect on proliferation of IMP-1-negative cells. 

PMID- 24108121
TI  - Amino acid composition of proteins reduces deleterious impact of mutations.
AB  - The evolutionary origin of amino acid occurrence frequencies in proteins
      (composition) is not yet fully understood. We suggest that protein composition
      works alongside the genetic code to minimize impact of mutations on protein
      structure. First, we propose a novel method for estimating thermodynamic
      stability of proteins whose sequence is constrained to a fixed composition.
      Second, we quantify the average deleterious impact of substituting one amino acid
      with another. Natural proteome compositions are special in at least two ways: 1)
      Natural compositions do not generate more stable proteins than the average random
      composition, however, they result in proteins that are less susceptible to damage
      from mutations. 2) Natural proteome compositions that result in more stable
      proteins (i.e. those of thermophiles) are also tuned to have a higher tolerance
      for mutations. This is consistent with the observation that environmental factors
      selecting for more stable proteins also enhance the deleterious impact of
      mutations. 

PMID- 24108122
TI  - Recognition of bisecting N-acetylglucosamine: structural basis for asymmetric
      interaction with the mouse lectin dendritic cell inhibitory receptor 2.
AB  - Dendritic cell inhibitory receptor 2 (DCIR2) is a C-type lectin expressed on
      classical dendritic cells. We recently identified the unique ligand specificity
      of mouse DCIR2 (mDCIR2) toward biantennary complex-type glycans containing
      bisecting N-acetylglucosamine (GlcNAc). Here, we report the crystal structures of
      the mDCIR2 carbohydrate recognition domain in unliganded form as well as in
      complex with an agalactosylated complex-type N-glycan unit carrying a bisecting
      GlcNAc residue. Bisecting GlcNAc and the alpha1-3 branch of the biantennary
      oligosaccharide asymmetrically interact with canonical and non-canonical mDCIR2
      residues. Ligand-protein interactions occur directly through mDCIR2
      characteristic amino acid residues as well as via a calcium ion and water
      molecule. Our structural and biochemical data elucidate for the first time the
      unique binding mode of mDCIR2 for bisecting GlcNAc-containing glycans, a mode
      that contrasts sharply with that of other immune C-type lectin receptors such as
      DC-SIGN. 

PMID- 24108123
TI  - Topogenesis and homeostasis of fatty acyl-CoA reductase 1.
AB  - Peroxisomal fatty acyl-CoA reductase 1 (Far1) is essential for supplying fatty
      alcohols required for ether bond formation in ether glycerophospholipid
      synthesis. The stability of Far1 is regulated by a mechanism that is dependent on
      cellular plasmalogen levels. However, the membrane topology of Far1 and how Far1
      is targeted to membranes remain largely unknown. Here, Far1 is shown to be a
      peroxisomal tail-anchored protein. The hydrophobic C terminus of Far1 binds to
      Pex19p, a cytosolic receptor harboring a C-terminal CAAX motif, which is
      responsible for the targeting of Far1 to peroxisomes. Far1, but not Far2, was
      preferentially degraded in response to the cellular level of plasmalogens.
      Experiments in which regions of Far1 or Far2 were replaced with the corresponding
      region of the other protein showed that the region flanking the transmembrane
      domain of Far1 is required for plasmalogen-dependent modulation of Far1
      stability. Expression of Far1 increased plasmalogen synthesis in wild-type
      Chinese hamster ovary cells, strongly suggesting that Far1 is a rate-limiting
      enzyme for plasmalogen synthesis. 

PMID- 24108124
TI  - FBH1 helicase disrupts RAD51 filaments in vitro and modulates homologous
      recombination in mammalian cells.
AB  - Efficient repair of DNA double strand breaks and interstrand cross-links requires
      the homologous recombination (HR) pathway, a potentially error-free process that
      utilizes a homologous sequence as a repair template. A key player in HR is RAD51,
      the eukaryotic ortholog of bacterial RecA protein. RAD51 can polymerize on DNA to
      form a nucleoprotein filament that facilitates both the search for the homologous
      DNA sequences and the subsequent DNA strand invasion required to initiate HR.
      Because of its pivotal role in HR, RAD51 is subject to numerous positive and
      negative regulatory influences. Using a combination of molecular genetic,
      biochemical, and single-molecule biophysical techniques, we provide mechanistic
      insight into the mode of action of the FBH1 helicase as a regulator of RAD51
      dependent HR in mammalian cells. We show that FBH1 binds directly to RAD51 and is
      able to disrupt RAD51 filaments on DNA through its ssDNA translocase function.
      Consistent with this, a mutant mouse embryonic stem cell line with a deletion in
      the FBH1 helicase domain fails to limit RAD51 chromatin association and shows
      hyper-recombination. Our data are consistent with FBH1 restraining RAD51 DNA
      binding under unperturbed growth conditions to prevent unwanted or unscheduled
      DNA recombination. 

PMID- 24108125
TI  - Monopolar spindle 1 (MPS1) protein-dependent phosphorylation of RecQ-mediated
      genome instability protein 2 (RMI2) at serine 112 is essential for BLM-Topo III
      alpha-RMI1-RMI2 (BTR) protein complex function upon spindle assembly checkpoint
      (SAC) activation during mitosis.
AB  - Genomic instability and a predisposition to cancer are hallmarks of Bloom
      syndrome, an autosomal recessive disease arising from mutations in the BLM gene.
      BLM is a RecQ helicase component of the BLM-Topo III alpha-RMI1-RMI2 (BTR)
      complex, which maintains chromosome stability at the spindle assembly checkpoint
      (SAC). Other members of the BTR complex include Topo IIIa, RMI1, and RMI2. All
      members of the BTR complex are essential for maintaining the stable genome.
      Interestingly, the BTR complex is posttranslationally modified upon SAC
      activation during mitosis, but its significance remains unknown. In this study,
      we show that two proteins that interact with BLM, RMI1 and RMI2, are
      phosphorylated upon SAC activation, and, like BLM, RMI1, and RMI2, are
      phosphorylated in an MPS1-dependent manner. An S112A mutant of RMI2 localized
      normally in cells and was found in SAC-induced coimmunoprecipitations of the BTR
      complex. However, in RMI2-depleted cells, an S112A mutant disrupted the mitotic
      arrest upon SAC activation. The failure of cells to maintain mitotic arrest, due
      to lack of phosphorylation at Ser-112, results in high genomic instability
      characterized by micronuclei, multiple nuclei, and a wide distribution of
      aberrantly segregating chromosomes. We found that the S112A mutant of RMI2 showed
      defects in redistribution between the nucleoplasm and nuclear matrix. The
      phosphorylation at Ser-112 of RMI2 is independent of BLM and is not required for
      the stability of the BTR complex, BLM focus formation, and chromatin targeting in
      response to replication stress. Overall, this study suggests that the
      phosphorylation of the BTR complex is essential to maintain a stable genome. 

PMID- 24108127
TI  - Structure of the bacterial deacetylase LpxC bound to the nucleotide reaction
      product reveals mechanisms of oxyanion stabilization and proton transfer.
AB  - The emergence of antibiotic-resistant strains of pathogenic bacteria is an
      increasing threat to global health that underscores an urgent need for an
      expanded antibacterial armamentarium. Gram-negative bacteria, such as Escherichia
      coli, have become increasingly important clinical pathogens with limited
      treatment options. This is due in part to their lipopolysaccharide (LPS) outer
      membrane components, which dually serve as endotoxins while also protecting Gram
      negative bacteria from antibiotic entry. The LpxC enzyme catalyzes the committed
      step of LPS biosynthesis, making LpxC a promising target for new antibacterials.
      Here, we present the first structure of an LpxC enzyme in complex with the
      deacetylation reaction product, UDP-(3-O-(R-3-hydroxymyristoyl))-glucosamine.
      These studies provide valuable insight into recognition of substrates and
      products by LpxC and a platform for structure-guided drug discovery of broad
      spectrum Gram-negative antibiotics. 

PMID- 24108126
TI  - Carboxypeptidase M is a positive allosteric modulator of the kinin B1 receptor.
AB  - Ligand binding to extracellular domains of G protein-coupled receptors can result
      in novel and nuanced allosteric effects on receptor signaling. We previously
      showed that the protein-protein interaction of carboxypeptidase M (CPM) and kinin
      B1 receptor (B1R) enhances B1R signaling in two ways; 1) kinin binding to CPM
      causes a conformational activation of the B1R, and 2) CPM-generated des-Arg-kinin
      agonist is efficiently delivered to the B1R. Here, we show CPM is also a positive
      allosteric modulator of B1R signaling to its agonist, des-Arg(10)-kallidin
      (DAKD). In HEK cells stably transfected with B1R, co-expression of CPM enhanced
      DAKD-stimulated increases in intracellular Ca(2+) or phosphoinositide turnover by
      a leftward shift of the dose-response curve without changing the maximum. CPM
      increased B1R affinity for DAKD by ~5-fold but had no effect on basal B1R
      dependent phosphoinositide turnover. Soluble, recombinant CPM bound to HEK cells
      expressing B1Rs without stimulating receptor signaling. CPM positive allosteric
      action was independent of enzyme activity but depended on interaction of its C
      terminal domain with the B1R extracellular loop 2. Disruption of the CPM/B1R
      interaction or knockdown of CPM in cytokine-treated primary human endothelial
      cells inhibited the allosteric enhancement of CPM on B1R DAKD binding or ERK1/2
      activation. CPM also enhanced the DAKD-induced B1R conformational change as
      detected by increased intramolecular fluorescence or bioluminescence resonance
      energy transfer. Thus, CPM binding to extracellular loop 2 of the B1R results in
      positive allosteric modulation of B1R signaling, and disruption of this
      interaction could provide a novel therapeutic approach to reduce pathological B1R
      signaling. 

PMID- 24108128
TI  - Structural basis for the recognition of mycolic acid precursors by KasA, a
      condensing enzyme and drug target from Mycobacterium tuberculosis.
AB  - The survival of Mycobacterium tuberculosis depends on mycolic acids, very long
      alpha-alkyl-beta-hydroxy fatty acids comprising 60-90 carbon atoms. However,
      despite considerable efforts, little is known about how enzymes involved in
      mycolic acid biosynthesis recognize and bind their hydrophobic fatty acyl
      substrates. The condensing enzyme KasA is pivotal for the synthesis of very long
      (C38-42) fatty acids, the precursors of mycolic acids. To probe the mechanism of
      substrate and inhibitor recognition by KasA, we determined the structure of this
      protein in complex with a mycobacterial phospholipid and with several
      thiolactomycin derivatives that were designed as substrate analogs. Our
      structures provide consecutive snapshots along the reaction coordinate for the
      enzyme-catalyzed reaction and support an induced fit mechanism in which a wide
      cavity is established through the concerted opening of three gatekeeping residues
      and several alpha-helices. The stepwise characterization of the binding process
      provides mechanistic insights into the induced fit recognition in this system and
      serves as an excellent foundation for the development of high affinity KasA
      inhibitors. 

PMID- 24108129
TI  - The E1015K variant in the synprint region of the CaV2.1 channel alters channel
      function and is associated with different migraine phenotypes.
AB  - Mutations in the CACNA1A gene, which encodes the pore-forming alpha1A subunit of
      the CaV2.1 voltage-gated calcium channel, cause a number of human neurologic
      diseases including familial hemiplegic migraine. We have analyzed the functional
      impact of the E1015K amino acid substitution located in the "synprint" domain of
      the alpha1A subunit. This variant was identified in two families with hemiplegic
      migraine and in one patient with migraine with aura. The wild type (WT) and the
      E1015K forms of the GFP-tagged alpha1A subunit were expressed in cultured
      hippocampal neurons and HEK cells to understand the role of the variant in the
      transport activity and physiology of CaV2.1. The E1015K variant does not alter
      CaV2.1 protein expression, and its transport to the cell surface and synaptic
      terminals is similar to that observed for WT channels. Electrophysiological data
      demonstrated that E1015K channels have increased current density and
      significantly altered inactivation properties compared with WT. Furthermore, the
      SNARE proteins syntaxin 1A and SNAP-25 were unable to modulate voltage-dependent
      inactivation of E1015K channels. Overall, our findings describe a genetic variant
      in the synprint site of the CaV2.1 channel which is characterized by a gain-of
      function and associated with both hemiplegic migraine and migraine with aura in
      patients. 

PMID- 24108130
TI  - New hyperekplexia mutations provide insight into glycine receptor assembly,
      trafficking, and activation mechanisms.
AB  - Hyperekplexia is a syndrome of readily provoked startle responses, alongside
      episodic and generalized hypertonia, that presents within the first month of
      life. Inhibitory glycine receptors are pentameric ligand-gated ion channels with
      a definitive and clinically well stratified linkage to hyperekplexia. Most
      hyperekplexia cases are caused by mutations in the alpha1 subunit of the human
      glycine receptor (hGlyR) gene (GLRA1). Here we analyzed 68 new unrelated
      hyperekplexia probands for GLRA1 mutations and identified 19 mutations, of which
      9 were novel. Electrophysiological analysis demonstrated that the dominant
      mutations p.Q226E, p.V280M, and p.R414H induced spontaneous channel activity,
      indicating that this is a recurring mechanism in hGlyR pathophysiology. p.Q226E,
      at the top of TM1, most likely induced tonic activation via an enhanced
      electrostatic attraction to p.R271 at the top of TM2, suggesting a structural
      mechanism for channel activation. Receptors incorporating p.P230S (which is
      heterozygous with p.R65W) desensitized much faster than wild type receptors and
      represent a new TM1 site capable of modulating desensitization. The recessive
      mutations p.R72C, p.R218W, p.L291P, p.D388A, and p.E375X precluded cell surface
      expression unless co-expressed with alpha1 wild type subunits. The recessive
      p.E375X mutation resulted in subunit truncation upstream of the TM4 domain.
      Surprisingly, on the basis of three independent assays, we were able to infer
      that p.E375X truncated subunits are incorporated into functional hGlyRs together
      with unmutated alpha1 or alpha1 plus beta subunits. These aberrant receptors
      exhibit significantly reduced glycine sensitivity. To our knowledge, this is the
      first suggestion that subunits lacking TM4 domains might be incorporated into
      functional pentameric ligand-gated ion channel receptors. 

PMID- 24108132
TI  - Long-term exposure to excessive iodine from water is associated with thyroid
      dysfunction in children.
AB  - Previous studies have indicated an association between iodine excess and
      increased incidence of thyroid dysfunction in adults. However, there have been
      few studies on how the intake of excessive iodine affects thyroid function in
      children. The objective of this study was to assess the effects of a long-term
      exposure to excessive iodine on thyroid dysfunction in children. Urinary iodine
      concentration (UIC) and thyroid function in 371 children from a high iodine (HI)
      area (water iodine: 150-963 MUg/L) and 150 children from an adequate iodine (AI)
      area (water iodine: 12.8-50.9 MUg/L) were measured. The water iodine
      concentration in the HI area was higher than that in the AI area (P < 0.001) and
      the median urinary iodine concentration of children in the HI area was 1030
      MUg/L, which was 8.6 times that of children in the AI area (123 MUg/L) (P <
      0.001). Children in the HI area had a higher concentration of sensitive thyroid
      stimulating hormone and higher positivity of both thyroid peroxidase antibody
      (TPOAb) and thyroglobulin antibody (TGAb). The prevalence of thyroid diseases was
      higher in HI area children than that in AI area children (P = 0.000), especially
      subclinical hypothyroidism (SCH; P = 0.004). A body mass index (BMI) of >= 22.3
      kg/m(2) was associated with the incidence of SCH (OR: 5.51; 95% CI: 1.52, 19.9; P
      = 0.009). UIC >= 600 MUg/L (OR: 3.62; 95% CI: 1.22, 10.8; P = 0.024) and TPOAb or
      TGAb-positivity (Ab+ OR: 6.48; 95% CI: 1.78, 23.6; P = 0.005) in children were
      significantly and independently associated with SCH. Interactions between UIC >=
      800 MUg/L and Ab+ (P-interaction = 0.004) were found. Furthermore, increased
      thyroid volume was correlated with higher UIC (beta = 0.22; P = 0.002). Excessive
      iodine intake in children in HI areas is associated with impaired thyroid
      function; UIC >= 600 MUg/L and Ab+ are the risk factors for SCH. Effective
      measures need to be taken for reducing excessive iodine intake.

PMID- 24108131
TI  - Fish oil supplementation ameliorates fructose-induced hypertriglyceridemia and
      insulin resistance in adult male rhesus macaques.
AB  - Fish oil (FO) is a commonly used supplemental source of eicosapentaenoic acid
      (EPA) and docosahexaenoic acid (DHA), 2 n-3 (omega-3) polyunsaturated fatty acids
      (PUFAs) that have been shown to have a variety of health benefits considered to
      be protective against cardiometabolic diseases. Although the effects of EPA and
      DHA on lipid metabolism have been extensively studied, not all of the metabolic
      effects of FO-derived n-3 PUFAs have been characterized. Our laboratory recently
      showed that a high-fructose diet in rhesus monkeys induces the features of
      metabolic syndrome (MetS) similar to those observed in humans. Thus, we
      specifically wanted to evaluate the effects of FO in rhesus monkeys fed a high
      fructose diet and hypothesized that FO supplementation would mitigate the
      development of fructose-induced insulin resistance, dyslipidemia, and other
      cardiometabolic risk factors. In this study, adult monkeys (aged 12-20 y)
      received either a standard unpurified diet plus 75 g fructose/d (control group; n
      = 9) or a standard unpurified diet, 75 g fructose/d, and 4 g FO (16% EPA + 11%
      DHA)/d (treatment group; n = 10) for 6 mo. Importantly, our results showed that
      daily FO supplementation in the monkeys prevented fructose-induced
      hypertriglyceridemia and insulin resistance as assessed by intravenous-glucose
      tolerance testing (P <= 0.05). Moreover, FO administration in the monkeys
      prevented fructose-induced increases in plasma apolipoprotein (Apo)C3, ApoE, and
      leptin concentrations and attenuated decreases in circulating adropin
      concentrations (P <= 0.05). No differences between the control and FO-treated
      monkeys were observed in body weight, lean mass, fat mass, or fasting glucose,
      insulin, and adiponectin concentrations. In conclusion, FO administration in a
      nonhuman primate model of diet-induced MetS ameliorates many of the adverse
      changes in lipid and glucose metabolism induced by chronic fructose consumption.

PMID- 24108133
TI  - Intrauterine-like growth rates can be achieved with premixed parenteral nutrition
      solution in preterm infants.
AB  - Growth failure in neonatal intensive care units is a major challenge for
      pediatricians and neonatologists. The use of early "aggressive" parenteral
      nutrition (PN), with >2.5 g/(kg .d) of amino acids and at least 40 kcal/(kg .d)
      of energy from the first day of life, has been shown to provide nutritional
      intakes in the range recommended by international guidelines, reducing
      nutritional deficit and the incidence of postnatal growth restriction in preterm
      infants. However, nutritional practices and adherence to recommendations may vary
      in different hospitals. Two ready-to-use (RTU), premixed parenteral solutions
      (PSs) designed for preterm infants have been prospectively evaluated: a binary
      RTU premixed PS from our hospital pharmacy and a commercially premixed 3-chamber
      bag (Baxter Healthcare). These premixed PSs provide nitrogen and energy intakes
      in the range of the most recent recommendations, reducing or eliminating the
      early cumulative nutritional deficit in very-low-birth-weight infants, and
      avoiding the development of postnatal growth restriction. A further rationale for
      RTU premixed PSs is that preterm infants require balanced PN that contains not
      only amino acids and energy but also minerals and electrolytes from the first day
      of life in order to reduce the incidence of metabolic disorders frequently
      reported in extremely-low-birth-weight infants during the early weeks of life. 

PMID- 24108134
TI  - Differential bioavailability, clearance, and tissue distribution of the acyclic
      tomato carotenoids lycopene and phytoene in mongolian gerbils.
AB  - Lycopene (LYC) is the major tomato carotenoid and is the focus of substantial
      research. Phytoene (PE), a minor tomato carotenoid, is found in human blood and
      tissues in similar concentrations to LYC. To determine which metabolic
      differences underlie this phenomenon, Mongolian gerbils (Meriones unguiculatus, n
      = 56) were fed control or tomato powder (TP)-containing diets (to establish
      steady-state serum and tissue carotenoid concentrations similar to tomato-fed
      humans) for 26 d. The TP-fed gerbils were then provided either a single, oral,
      cottonseed oil (CO) vehicle dose and tissues were collected at 6 h or they were
      provided unlabeled PE or LYC in CO and tissues were evaluated at 6, 12, or 24 h.
      In vehicle-dosed, TP-fed gerbils, LYC was the major carotenoid (>= 55%
      carotenoids) in liver, spleen, testes, and the prostate-seminal vesicle complex,
      whereas PE was the major serum and adipose carotenoid (>= 37% total carotenoid)
      and phytofluene was the major carotenoid (>= 38%) in adrenals and lungs. PE
      dosing increased hepatic, splenic, and serum PE concentrations compared with
      vehicle dosing (P < 0.05) from 6 to 24 h, whereas LYC dosing increased only serum
      LYC at 6 and 12 h (P < 0.05) compared with vehicle dosing. This suggested PE was
      more bioavailable and cleared more slowly than LYC. To precisely track absorptive
      and distributive differences, (14)C-PE or (14)C-LYC (n = 2/group) was provided to
      TP-fed gerbils. Bioavailability assessed by carcass (14)C-content was 23% for PE
      and 8% for LYC. Nearly every extra-hepatic tissue accumulated greater dose
      radioactivity after (14)C-PE than (14)C-LYC dosing. Thus, LYC and PE, which
      structurally differ only by saturation, pharmacokinetically differ in
      bioavailability, tissue deposition, and clearance.

PMID- 24108136
TI  - A systematic review of practice surveys on parenteral nutrition for preterm
      infants.
AB  - Significant efforts have been made to improve the nutritional support of preterm
      infants in neonatal intensive care units (NICUs) to avoid cumulative nutritional
      deficits, reduce postnatal growth restriction, and promote optimal long-term
      development. The objective of this systematic review was to compare the
      characteristics and results of all surveys published in the past 10 y (2002-2012)
      that used a questionnaire to survey at least 2 NICUs receiving preterm infants
      with an intention to treat with parenteral nutrition (PN) and that reported
      information on at least 1 macronutrient. A total of 6 surveys were identified,
      which were conducted in the United States (n = 2) or Europe (n = 4). There was
      wide variability in the response rate (23-100%), with a higher response rate in
      the smaller studies (81-100%; 8-64 respondents) compared with the larger studies
      (23-58%; 296-809 respondents). Large differences were observed in the nutritional
      protocols both among the NICUs in the individual surveys and between surveys. PN
      was initiated on the first day of life (DOL) by only 24-54% of respondents (4
      surveys) and within the second DOL by 67-94% of respondents (5 surveys). Lipids
      were initiated before the third DOL for 46-96% of respondents (3 surveys). The
      results of this systematic review suggest that continuous education is needed and
      that greater efforts are required to disseminate and implement guidelines.
      Repeated surveys are needed to highlight trends in clinical practices and level
      of compliance of NICUs with existing guidelines. 

PMID- 24108135
TI  - Apolipoprotein A2 polymorphism interacts with intakes of dairy foods to influence
      body weight in 2 U.S. populations.
AB  - The interaction between a functional apolipoprotein A2 gene (APOA2) variant and
      saturated fatty acids (SFAs) for the outcome of body mass index (BMI) is among
      the most widely replicated gene-nutrient interactions. Whether this interaction
      can be extrapolated to food-based sources of SFAs, specifically dairy foods, is
      unexplored. Cross-sectional analyses were performed in 2 U.S. population-based
      samples. We evaluated interactions between dairy foods and APOA2 -265T > C
      (rs5082) for BMI in the Boston Puerto Rican Health Study (n = 955) and tested for
      replication in the Genetics of Lipid Lowering Drugs and Diet Network (GOLDN)
      study (n = 1116). Dairy products were evaluated as total dairy, higher-fat dairy
      (>1%), and low-fat dairy (<= 1%) in servings per day, dichotomized into high and
      low based on each population median and also as continuous variables. We
      identified a statistically significant interaction between the APOA2 -265T > C
      variant and higher-fat dairy food intake in the Boston Puerto Ricans (P
      interaction = 0.028) and replicated this relation in the GOLDN study (P
      interaction = 0.001). In both groups, individuals with the previously
      demonstrated SFA-sensitive genotype (CC) who consumed a greater amount of higher
      fat dairy foods had greater BMI (P = 0.013 in Boston Puerto Ricans; P = 0.0007 in
      GOLDN women) compared with those consuming less of the higher-fat dairy foods.
      The results expand the understanding of the metabolic influence of dairy
      products, an important food group for which variable relations to body weight may
      be in part genetically based. Moreover, these findings suggest that other
      strongly demonstrated gene-nutrient relations might be investigated through
      appropriate food-based, translatable avenues and may be relevant to dietary
      management of obesity.

PMID- 24108137
TI  - The present challenges of parenteral nutrition in preterm infants and children.
AB  - The goal of pediatricians involved in the nutritional management of preterm
      infants is to mimic intrauterine growth and to obtain a functional outcome
      comparable to that for infants born at term. Appropriate administration of
      nutrients in the first few days to weeks of life will reduce the growth
      restriction that is frequently observed. Existing guidelines advise providing
      preterm infants with both amino acids and lipids from birth onward. Despite this
      knowledge, many hospital units do not comply with these guidelines. Further
      improvement of the quality of the composition of parenteral solutions for both
      neonates as well as older children should be the subject of further research. 

PMID- 24108138
TI  - Commercially premixed 3-chamber bags for pediatric parenteral nutrition are
      available for hospitalized children.
AB  - Hospitalized children are vulnerable to malnutrition during serious illness or
      recovery from injury and are at subsequent risk of increased morbidity and growth
      retardation. In cases in which enteral nutrition is not possible, parenteral
      nutrition (PN) can be used to ensure that patients at nutritional risk receive
      appropriate amounts of macro- and micronutrients. Nutritional needs cannot be met
      by 1 standard PN formulation in pediatric patients (term to 18 y) because of the
      wide range of needs according to age, weight, degree of maturity, and disease
      state. Preparation of individualized PN is associated with several limitations,
      including prescribing errors, stability issues, and risk of infection. These
      risks may be avoided by the availability of a range of pediatric PN formulations
      provided as commercial premixed 3-chamber bags (3-CBs). These 3-CBs were
      developed in conjunction with experienced neonatologists and pediatricians in
      accordance with international guidelines. A prospective study has previously
      shown the practical handling and ease of use of 2 formulations of these 3-CBs, 1
      designed for term infants and toddlers up to 2 y of age and 1 for children and
      adolescents aged 2-18 y. The majority of pharmacists and nurses described the 3
      CB as easy to use and favored it over individual bottles, bags compounded on the
      ward, ready-to-use compounded bags, and premixes prepared by the pharmacy and
      tailored to patient needs. These formulations offer a means of improving the
      quality of care in hospital pediatric units, particularly in the absence of a
      nutrition support team. 

PMID- 24108139
TI  - Unexpected isocyanide-based cascade cycloaddition reaction with
      methyleneindolinone.
AB  - An unprecedented cascade reaction of isocyanide and methyleneindolinone has been
      established, which represents a novel and different reaction mode. This present
      transformation involves the ring-opening of methyleneindolinone and the
      construction of two other new rings simultaneously in an atom-economic manner. 

PMID- 24108140
TI  - Genogroup I avian picobirnavirus detected in Brazilian broiler chickens: a
      molecular epidemiology study.
AB  - Picobirnavirus (PBV) belongs to the family Picobirnaviridae. Picobirnaviruses
      contain a bisegmented dsRNA genome that is non-enveloped. A total of 85 pooled
      faecal samples were collected from the poultry of 37 farms from the Metropolitan
      Mesoregion of Belem (MMB), Para state, Brazil. The viral RNA from each sample was
      analysed by PAGE and reverse transcriptase PCR (RT-PCR). For each county
      affected, at least one positive sample was selected, cloned and sequenced. The
      samples showed a positivity of 15.3 % (13/85) by PAGE and 49.4 % (42/85) by RT
      PCR. Sequencing of these strains demonstrated a considerable RdRp gene
      heterogeneity that ranged from 56.1 to 100 % at the nucleotide level compared
      with prototypes of different species and water sewage, and from 50.3 to 100 %
      among themselves. Avian picobirnavirus (AvPBV) was detected in MMB broiler farms
      and showed a heterogeneous relationship with the prototypes used. This report
      includes what is believed to be the first gene sequencing of AvPBV in Brazilian
      broiler chickens. 

PMID- 24108141
TI  - Phylogenetic analysis of Merkel cell polyomavirus based on full-length LT and VP1
      gene sequences derived from neoplastic tumours in Japanese patients.
AB  - Most Merkel cell polyomavirus (MCPyV) gene sequences have been reported from
      Western countries and few data are available for the virus sequences from other
      geographical areas, especially Asia. Thus, we performed phylogenetic analyses
      based on the nucleotide sequences of the full-length large T-antigen (LT) and
      viral protein 1 (VP1) genes derived from a variety of cancers in Japanese
      patients and compared them with sequences from Caucasians. The LT and VP1 gene
      based phylogenetic trees identified two main genetic clades. One clade comprised
      strains isolated from Caucasians, whereas all of the Japanese tumour-derived
      MCPyV strains belonged to another clade. These findings confirm that most of the
      MCPyV strains present in Japan form a clade, distinct from Caucasian strains. 

PMID- 24108142
TI  - Substrate ectodomain is critical for substrate preference and inhibition of gamma
      secretase.
AB  - Understanding the substrate recognition mechanism of gamma-secretase is a key
      step for establishing substrate-specific inhibition of amyloid beta-protein
      (Abeta) production. However, it is widely believed that gamma-secretase is a
      promiscuous protease and that its substrate-specific inhibition is elusive. Here
      we show that gamma-secretase distinguishes the ectodomain length of substrates
      and preferentially captures and cleaves substrates containing a short ectodomain.
      We also show that a subset of peptides containing the CDCYCxxxxCxCxSC motif binds
      to the amino terminus of C99 and inhibits Abeta production in a substrate
      specific manner. Interestingly, these peptides suppress beta-secretase-dependent
      cleavage of APP, but not that of sialyltransferase 1. Most importantly,
      intraperitoneal administration of peptides into mice results in a significant
      reduction in cerebral Abeta levels. This report provides direct evidence of the
      substrate preference of gamma-secretase and its mechanism. Our results
      demonstrate that the ectodomain of C99 is a potent target for substrate-specific
      anti-Abeta therapeutics to combat Alzheimer's disease. 

PMID- 24108144
TI  - Patient safety in plastic surgery: identifying areas for quality improvement
      efforts.
AB  - Improving quality of health care is a global priority. Before quality benchmarks
      are established, we first must understand rates of adverse events (AEs). This
      project assessed risk-adjusted rates of inpatient AEs for soft tissue
      reconstructive procedures.Patients receiving soft tissue reconstructive
      procedures from 2005 to 2010 were extracted from the Nationwide Inpatient Sample.
      Inpatient AEs were identified using patient safety indicators (PSIs), established
      measures developed by Agency for Healthcare Research and Quality.We identified
      409,991 patients with soft tissue reconstruction and 16,635 (4.06%) had a PSI
      during their hospital stay. Patient safety indicators were associated with
      increased risk-adjusted mortality, longer length of stay, and decreased routine
      disposition (P < 0.01). Patient characteristics associated with a higher risk
      adjusted rate per 1000 patients at risk included older age, men, nonwhite, and
      public payer (P < 0.05). Overall, plastic surgery patients had significantly
      lower risk-adjusted rate compared to other surgical inpatients for all events
      evaluated except for failure to rescue and postoperative hemorrhage or hematoma,
      which were not statistically different. Risk-adjusted rates of hematoma
      hemorrhage were significantly higher in patients receiving size-reduction
      surgery, and these rates were further accentuated when broken down by sex and
      payer. In general, plastic surgery patients had lower rates of in-hospital AEs
      than other surgical disciplines, but PSIs were not uncommon. With the
      establishment of national basal PSI rates in plastic surgery patients, benchmarks
      can be devised and target areas for quality improvement efforts identified.
      Further prospective studies should be designed to elucidate the drivers of AEs
      identified in this population.

PMID- 24108146
TI  - Uncovering the role of elementary processes in network evolution.
AB  - The growth and evolution of networks has elicited considerable interest from the
      scientific community and a number of mechanistic models have been proposed to
      explain their observed degree distributions. Various microscopic processes have
      been incorporated in these models, among them, node and edge addition, vertex
      fitness and the deletion of nodes and edges. The existing models, however, focus
      on specific combinations of these processes and parameterize them in a way that
      makes it difficult to elucidate the role of the individual elementary mechanisms.
      We therefore formulated and solved a model that incorporates the minimal
      processes governing network evolution. Some contribute to growth such as the
      formation of connections between existing pair of vertices, while others capture
      deletion; the removal of a node with its corresponding edges, or the removal of
      an edge between a pair of vertices. We distinguish between these elementary
      mechanisms, identifying their specific role on network evolution. 

PMID- 24108147
TI  - Detection of multiple stresses in Scots pine growing at post-mining sites using
      visible to near-infrared spectroscopy.
AB  - Heavy metal contamination, low pH and high substrate heterogeneity are multiple
      stress factors that often occur at the post-mining sites and make difficult the
      biological reclamation. Efficient tools for detection of the status of reclaimed
      vegetation at post-mining sites are needed. We tested the potential of visible to
      near-infrared (VNIR) spectroscopy to detect multiple stresses in Scots pine
      (Pinus sylvestris L.) at acidic substrates rich in As. The needle chemical traits
      (chlorophyll a + b - Cab; carotenoids - Car; Car/Cab; relative water content -
      RWC; soluble phenolics; lignin contents) were tested for sensitivity to different
      soil conditions of post-mining sites. For Scots pine growing on degraded
      substrates, at least three non-specific stress indicators (RWC, photosynthetic
      pigments and phenolics) are required to achieve good site separability
      corresponding to the stress load. We constructed and validated empirical models
      of selected needle chemical traits using VNIR spectroscopy: calibration of Cab
      (R(2) = 0.97, RMSE = 0.17 mg g(-1)), RWC (R(2) = 0.88, RMSE = 1.41 mg g(-1)), Car
      (R(2) = 0.66, RMSE = 0.08 mg g(-1)), phenolics (R(2) = 0.64, RMSE = 23.01 mg g(
      1)) and lignin (R(2) = 0.45, RMSE = 3.32 mg g(-1)). The reflectance data yielded
      comparable site separability with the separability calculated from the laboratory
      data. The presented approach has potential for large-scale monitoring of Scots
      pine status, thus, assessment of reclamation quality in post-mining regions using
      air-born or satellite hyperspectral data. 

PMID- 24108148
TI  - Pooled analysis of adjunct extended-release quetiapine fumarate in patients with
      major depressive disorder according to ongoing SSRI or SNRI treatment.
AB  - This pooled analysis evaluated the efficacy of extended-release quetiapine
      fumarate (quetiapine XR) adjunct to selective serotonin reuptake inhibitors
      (SSRIs) or serotonin-norepinephrine reuptake inhibitors (SNRIs) in patients with
      major depressive disorder (MDD). Pooled data were analyzed from two 6-week,
      double-blind, randomized, placebo-controlled trials of adjunct quetiapine XR (150
      and 300 mg/day) in patients with MDD and inadequate response to initial
      antidepressant monotherapy. This post-hoc analysis included evaluation of change
      from randomization at week 6 in Montgomery Asberg Depression Rating Scale (MADRS)
      total scores (primary endpoint), and week 6 MADRS response and remission rates
      for quetiapine XR as an adjunct to ongoing SSRI or SNRI. In total, 189, 178, and
      202 patients received quetiapine XR 150 mg/day+SSRI, 300 mg/day+SSRI, and
      placebo+SSRI, respectively, whereas 82, 90, and 76 patients, respectively,
      received quetiapine XR 150 mg/day+SNRI, 300 mg/day+SNRI, and placebo+SNRI. At
      week 6, quetiapine XR 150 mg/day+SSRI and 300 mg/day+SSRI reduced the MADRS total
      score from randomization versus placebo+SSRI [least squares mean (LSM) change, 
      14.70 (P<0.05) -14.72 (P<0.05) vs. -12.59, respectively]. Quetiapine XR 150
      mg/day+SNRI (LSM change, -14.68, P<0.01) and 300 mg/day+SNRI (LSM change, -14.99,
      P<0.01) also reduced the MADRS total score from randomization at week 6 versus
      placebo+SNRI (-10.77). In conclusion, in patients with MDD and inadequate
      response to ongoing antidepressant, adjunct quetiapine XR (150 and 300 mg/day)
      was effective in both SSRI and SNRI subgroups.

PMID- 24108149
TI  - Aripiprazole augmentation for major depressive disorder: dosing patterns in a
      naturalistic treatment setting.
AB  - This study investigated the dosing patterns for aripiprazole augmentation for
      major depressive disorder (MDD) in a naturalistic treatment setting. Between 1
      January 2009 and 31 March 2012, patients with a diagnosis of MDD who were
      receiving aripiprazole augmentation in conjunction with an ongoing antidepressant
      were recruited for this study. The electronic medical records and clinical data
      for a total of 276 patients were reviewed up to a year. The mean duration of
      aripiprazole augmentation was ~5 months; the mean time to the first increase of
      aripiprazole was about 3 weeks; and the mean initial, first up-titrated, maximal,
      and maintenance doses were 3.4, 4.2, 4.7, and 4.4 mg/day, respectively. The most
      frequent adverse events were insomnia, followed by anxiety and sedation. The
      current results indicate that the actual doses of aripiprazole augmentation with
      ongoing antidepressant for MDD should be lower than the doses used in placebo
      controlled clinical trials and those recommended by the US Food and Drug
      Administration. Adequately powered and well-controlled prospective studies are
      needed to better understand the exact role of low doses of aripiprazole
      augmentation in the treatment of MDD, particularly in routine practice. 

PMID- 24108150
TI  - AAV-encoded OTC activity persisting to adulthood following delivery to newborn
      spf(ash) mice is insufficient to prevent shRNA-induced hyperammonaemia.
AB  - Urea cycle defects presenting in the neonatal period with hyperammonaemia are
      associated with high morbidity and mortality, and necessitate liver
      transplantation for long-term management. Gene therapy is therefore an attractive
      possibility, with vectors based on adeno-associated virus (rAAV) currently
      showing exciting promise in liver-targeted clinical trials in adults. Successful
      use of rAAV vectors in infants, however, is more challenging as episomal rAAV
      genomes will be lost from proliferating hepatocytes during liver growth, leaving
      stable transgene expression dependent on the subset of vector genomes that
      undergo genomic integration. To explore this challenge, we exploited the
      partially ornithine transcarbamylase (OTC)-deficient spf(ash) mouse model and
      small hairpin RNA-mediated knockdown of residual endogenous OTC enzyme activity
      in adult mice that had received neonatal treatment with an OTC-encoding rAAV.
      This leaves mice reliant on vector-encoded OTC activity that has persisted from
      the newborn period. Despite stable transduction in approximately 8% of
      hepatocytes and residual vector-encoded OTC activity of up to 33% of wild-type,
      well above endogenous spf(ash) levels (5-7%), mice were not protected from
      hyperammonaemia. These data show that the distribution of OTC activity within the
      liver is critical and that rAAV vector re-delivery after early neonatal treatment
      is likely to be necessary for stable control of hyperammonaemia into adulthood. 

PMID- 24108151
TI  - Efficient siRNA transfection to the inner ear through the intact round window by
      a novel proteidic delivery technology in the chinchilla.
AB  - The use of small-interfering RNA (siRNA) has great potential for the development
      of drugs designed to knock down the expression of damage- or disease-causing
      genes. However, because of the high molecular weight and negative charge of
      siRNA, it is restricted from crossing the blood-cochlear barrier, which limits
      the concentration and size of molecules that are able to gain access to cells of
      the inner ear. Intratympanic approaches, which deliver siRNA to the middle ear,
      rely on permeation through the round window for access to the structures of the
      inner ear. We developed an innovative siRNA delivery recombination protein, TAT
      double-stranded RNA-binding domains (TAT-DRBDs), which can transfect Cy3-labeled
      siRNA into cells of the inner ear, including the inner and outer hair cells,
      crista ampullaris, macula utriculi and macula sacculi, through intact round
      window permeation in the chinchilla in vivo, and there were no apparent
      morphological damages for the time of observation. We also found that Cy3-labeled
      siRNA could directly enter spiral ganglion neurons and the epithelium of the
      stria vascularis independently; however, the mechanism is unknown. Therefore, as
      a non-viral vector, TAT-DRBD is a good candidate for the delivery of double
      stranded siRNAs for treating various inner ear ailments and preservation of
      hearing function. 

PMID- 24108152
TI  - Safety and efficacy of motor mapping utilizing short pulse train direct cortical
      stimulation.
AB  - BACKGROUND/AIMS: A major goal of intracranial surgery is to maximize resection
      while minimizing neurological morbidity, particularly motor dysfunction. Direct
      cortical stimulation (DCS) is a common intraoperative adjunct used to identify
      functional motor cortex. In this study, we report on the safety/efficacy of short
      pulse train DCS (direct cortical stimulation motor-evoked potential, dcMEP) for
      motor mapping and monitoring during intracranial surgery. METHODS: A
      retrospective analysis of 29 patients undergoing elective craniotomy for lesions
      near the motor cortex was performed. dcMEP mapping (40-120 V, 500-1,000 Hz, 5-9
      pulses/s, 1- to 3-ms interstimulus interval, monopolar, 50-MUs pulse width) was
      performed either alone (n = 29) or in addition to standard DCS (n = 6). Outcome
      measures were positive MEPs and the presence of seizures during stimulation.
      dcMEP-based continuous corticospinal tract (CST) monitoring was also performed.
      Changes in stimulation threshold and new postoperative neurological deficits were
      recorded. RESULTS: dcMEP mapping success was 96% and was not affected by
      preoperative motor status. Intraoperative seizure rates for dcMEP were 3% and
      were not related to preoperative seizure status. CST monitoring success rate was
      96%, and changes in stimulation threshold were predictive of new permanent motor
      deficits. CONCLUSIONS: dcMEP is an effective method for mapping motor function
      and may prove useful for continuous CST monitoring.

PMID- 24108153
TI  - Safety of the quadrivalent human papillomavirus vaccine.

PMID- 24108154
TI  - Time for open access to all medical documentation forms.

PMID- 24108155
TI  - Identifying brain tumours in children and young adults.

PMID- 24108156
TI  - The problem of selective briefings for a transparent NHS.

PMID- 24108157
TI  - Putting less emphasis on classifying mental disorders and more on collaborative
      working.

PMID- 24108158
TI  - Importance of the dynamics between patients with personality disorder and the
      doctors treating them.

PMID- 24108160
TI  - Bad medicine: non-ST elevation myocardial infarction.

PMID- 24108159
TI  - Autoimmune, neurological, and venous thromboembolic adverse events after
      immunisation of adolescent girls with quadrivalent human papillomavirus vaccine
      in Denmark and Sweden: cohort study.
AB  - OBJECTIVE: To assess the risk of serious adverse events after vaccination of
      adolescent girls with quadrivalent human papillomavirus (qHPV) vaccine. DESIGN:
      Register based cohort study. SETTING: Denmark and Sweden, October 2006 to
      December 2010. PARTICIPANTS: 997,585 girls aged 10-17, among whom 296,826
      received a total of 696,420 qHPV vaccine doses. MAIN OUTCOME MEASURES: Incident
      hospital diagnosed autoimmune, neurological, and venous thromboembolic events (53
      different outcomes) up to 180 days after each qHPV vaccine dose. Only events with
      at least five vaccine exposed cases were considered for further assessment. Rate
      ratios adjusted for age, country, calendar year, and parental country of birth,
      education, and socioeconomic status were estimated, comparing vaccinated and
      unvaccinated person time. For outcomes where the rate ratio was significantly
      increased, we regarded three criteria as signal strengthening: analysis based on
      20 or more vaccine exposed cases (reliability), rate ratio 3.0 or more
      (strength), and significantly increased rate ratio in country specific analyses
      (consistency). We additionally assessed clustering of events in time and
      estimated rate ratios for a risk period that started on day 181. RESULTS: Among
      the 53 outcomes, at least five vaccine exposed cases occurred in 29 and these
      were analysed further. Whereas the rate ratios for 20 of 23 autoimmune events
      were not significantly increased, exposure to qHPV vaccine was significantly
      associated with Behcet's syndrome, Raynaud's disease, and type 1 diabetes. Each
      of these three outcomes fulfilled only one of three predefined signal
      strengthening criteria. Furthermore, the pattern of distribution in time after
      vaccination was random for all three and the rate ratios for these outcomes in
      the period from day 181 after vaccination were similar to the rate ratios in the
      primary risk period. The rate ratios for five neurological events were not
      significantly increased and there were inverse associations with epilepsy (rate
      ratio 0.66, 95% confidence interval 0.54 to 0.80) and paralysis (0.56, 0.35 to
      0.90). There was no association between exposure to qHPV vaccine and venous
      thromboembolism (0.86, 0.55 to 1.36). CONCLUSIONS: This large cohort study found
      no evidence supporting associations between exposure to qHPV vaccine and
      autoimmune, neurological, and venous thromboembolic adverse events. Although
      associations for three autoimmune events were initially observed, on further
      assessment these were weak and not temporally related to vaccine exposure.
      Furthermore, the findings need to be interpreted considering the multiple
      outcomes assessed.

PMID- 24108161
TI  - Mandatory moaning.

PMID- 24108162
TI  - Response to Krogsboll and colleagues: NHS health checks or government by
      randomised controlled trial?

PMID- 24108163
TI  - Time to put right what is going wrong in the government's disability assessments.

PMID- 24108164
TI  - The word "cancer". Precancerous lesions are more accurately termed "dysplasia".

PMID- 24108165
TI  - Helping patients make the right decisions about treatment.

PMID- 24108166
TI  - New Care Quality Commission inspection regime is under-resourced.

PMID- 24108167
TI  - Trials of therapeutic communities in personality disorder are under way.

PMID- 24108168
TI  - Authors' reply to Pearce.

PMID- 24108169
TI  - Climate change: the challenge for healthcare professionals.

PMID- 24108170
TI  - Lister restaged: one sure step for science and safer surgery.

PMID- 24108171
TI  - Guidelines for collaboration with industry should be transparent.

PMID- 24108172
TI  - World Bank is urged to end support for social health insurance schemes.

PMID- 24108173
TI  - Canadian doctor is released from jail but stopped from leaving Egypt.

PMID- 24108174
TI  - Vaccine refusal may have contributed to California's 2010 pertussis outbreak,
      study finds.

PMID- 24108175
TI  - Imaging breakdown diagrams for bromobutyne isomers with photoelectron-photoion
      coincidence.
AB  - Internal energy selected C4H5Br(+) ions were prepared by vacuum ultraviolet
      photoionization from the bromobutyne constitutional isomers 4-bromo-1-butyne, 1
      bromo-2-butyne, and 3-bromo-1-butyne. The lowest energy dissociative
      photoionization channel is Br-loss. 1-Bromo-2-butyne and 3-bromo-1-butyne cations
      are not metastable, and based on the threshold photoionization breakdown diagrams
      and neutral internal energy distributions, 0 K appearance energies of E0 = 10.375
      +/- 0.010 and 10.284 +/- 0.010 eV are obtained, respectively. A kinetic shift has
      been observed in the Br loss of the 4-bromo-1-butyne cation, and the experimental
      dissociation rates were also modeled to obtain E0 = 10.616 +/- 0.030 eV. The
      energetics of the samples and nine C4H5 and C4H5(+) structures are explored using
      G4 theory, which suggests that only the staggered 4-bromo-1-butyne rotamer cation
      loses Br to form a high-energy cyclic C4H5(+) isomer, while the relative
      appearance energies indicate that 1-bromo-2-butyne and 3-bromo-1-butyne form the
      linear CH2CCCH3(+) ion. The subtraction scheme for hot electron suppression in
      threshold photoelectron-photoion coincidence (TPEPICO) is discussed, and is used
      to introduce velocity map imaging (VMI-)PEPICO and data analysis. The derived
      onsets and the dissociation rate curve show that modeling VMI-PEPICO data taken
      close above or below the disappearance energy of the parent ion to obtain imaging
      breakdown diagrams is a feasible approach also in the presence of a kinetic
      shift. Imaging breakdown diagrams are advantageous when signal levels are low or
      short acquisition times necessary, such as in the case of reactive intermediates
      or in time resolved experiments, and can also be used as a fast molecular
      thermometer. 

PMID- 24108176
TI  - Hydrodefluorination of carbon-fluorine bonds by the synergistic action of a
      ruthenium-palladium catalyst.
AB  - Catalytic hydrodefluorination of organic molecules is a major organometallic
      challenge, owing to the strength of C-F sigma bonds, and it is a process with
      multiple industrial applications. Here we report a new heterodimetallic ruthenium
      palladium complex based on a triazolyl-di-ylidene ligand. The complex is
      remarkably active in the hydrodefluorination of aromatic and aliphatic carbon
      fluorine bonds under mild reaction conditions. We observe that both metals are
      required to promote the reaction process. The overall process implies that the
      palladium fragment facilitates the C-F activation, whereas the ruthenium centre
      allows the reduction of the substrate via transfer hydrogenation from
      isopropanol/sodium t-butoxide. The activity of this heterodimetallic complex is
      higher than that shown by a mixture of the related homodimetallic complexes of
      ruthenium and palladium, demonstrating the catalytic benefits of the
      heterodimetallic complex linked by a single-frame ligand. 

PMID- 24108177
TI  - [The future of psychiatry: way out from a dead end (editorial)].

PMID- 24108178
TI  - [Differentiation between mild cognitive impairment and healthy elderly population
      using neuropsychological tests].
AB  - OBJECTIVE: Paired Associates Learning (PAL) test assesses brain functions in
      those brain regions affected earliest by Alzheimer's dementia. The aim of the
      present study was to assess the usability of our implementation of the PAL test
      for screening mild cognitive impairment. METHODOLOGY: Based on Petersen criteria,
      14 out of the 63 subjects were diagnosed with mild cognitive impairment.
      Visuospatial learning was assessed by our implementation of PAL test. The ability
      of the PAL test to differentiate between study groups was compared to the
      Addenbrook Cognitive Examination (ACE) and to the Mini Mental State Examination
      (MMSE). Linear logistic regression was used for statistical analysis, and the
      results are presented as Receiver Operating Characteristics (ROC) curves. All
      analyses were performed by SAS 9.2. RESULTS: All the results of
      neuropsychological tests differed significantly between the study groups.
      However, considerable difference could be detected between the tests regarding
      specificity and sensitivity. The PAL test reached the sensitivity of the ACE,
      while its specificity was slightly under the ACE. DISCUSSION: The PAL test
      developed in the framework of the present study is found to be able to
      differentiate between MCI and healthy controls. It outperformed the MMSE in terms
      of sensitivity and specificity, while it needs comparable time to perform. Its
      sensitivity, the important parameter for screening, is comparable to ACE, while
      it needs significantly shorter time and less assistance.

PMID- 24108179
TI  - [Current treatment of depression and agitation in the elderly -- clinical use of
      trazodone].
AB  - Due to their increasing frequency, mental disorders among the elderly have
      special importance in the clinical practice. In this article we summarize the
      characteristics, diagnostic problems and modern treatments of mental disorders
      (especially depression) in old age. As this period of life means special somatic
      and psychic features in people's condition, it may be difficult to find the most
      effective and well-tolerated treatment, especially in case of comorbid dementia
      or agitated behaviour. In this article we review the therapeutic experience with
      the SARI antidepressant trazodone. Clinical studies and everyday practice
      indicate that trazodone due to its special multifunctional receptorprofile can be
      particularly effective in the treatment of depression accompanied by severe
      insomnia and anxiety. Due to its special anxiolytic and sleep normalising effect
      and well-tolerated side effect profile trazodone is found to be clinically useful
      not only in the treatment of depression in the elderly, but also in the case of
      serious comorbidity with dementia or agitated behaviour. We also illustrate the
      possibilities of using trazodone in the everyday practice with the presentation
      of two case reports. Furthermore we review the viewpoints of complex therapy
      which facilitates the successful treatment of depression in the elderly and the
      restoration of quality of life. 

PMID- 24108181
TI  - Network analysis of neurotransmitter related human kinase genes: possible role of
      SRC, RAF1, PTK2B?
AB  - Previous co-expression analysis of human kinase genes highlighted 119 genes in
      neurotransmitter-related activity (based on Go:Terms). Using a merged interactome
      dataset, we analyzed the network of these Neurotransmitter Related Human Kinase
      Genes. Using the full interactome dataset we extended the network and calculating
      degrees and closeness centralities we identified SRC, MAPK1, RAF1, PTK2B and AKT1
      kinase genes as potentially relevant nodes which did not show relevant activity
      in the original experimental study. As AKT1 and MAPK1 have already been indicated
      in various neuronal functions, we hypothesize a potential direct or indirect role
      for SRC, RAF1, PTK2B genes in neurotransmission and in central nervous system
      signaling processes. 

PMID- 24108180
TI  - [Antidepressants, depression and suicide].
AB  - AIM: The goal of this paper is to analyse the complex relationship between
      antidepressants, depression and suicide. METHOD: Review and synthesis of the
      Hungarian and English language international literature, published on this topic
      in the last 15 years. RESULTS: Large-scale, retrospective and prospective,
      naturalistic ("real life") studies show that compared to patients without
      treatment antidepressants and mood stabilizers reduce the risk of completed and
      attempted suicide by about 80%. This anti-suicidal potential is significantly
      higher than the small increase in suicidality of patients taking antidepressants
      in placebo controlled randomized Phase II/III trials. New data show that based on
      clinical data this small subgroup can be identified and successfully treated
      using specific therapy. CONCLUSION: Suicidal behaviour in patients taking
      antidepressants is mostly the consequence of the lack of antidepressant effect
      and is rarely the result of suicide-inducing potential of antidepressants. This
      rare latter case is most frequently the consequence of antidepressant monotherapy
      of bipolar depression. Appropriate use of antidepressants and mood stabilizers
      plays a key role in suicide prevention of patients with affective disorders.

PMID- 24108182
TI  - [Combination of second generation antipsychotics -- case report].
AB  - Treatment guidelines suggest antipsychotic monotherapy in the treatment of
      psychosis. 20-40% of patients take combination therapy in clinical practice due
      to inadequate treatment response to monotherapy. First-generation antipsychotic
      monotherapy was ineffective in case of our patient who had severe psychotic
      symptoms. Switching to a second generation antipsychotic had partial therapeutic
      effect, the severe psychotic condition was persistent. For this reason the
      therapy was changed to olanzapine-clozapine combination. Due to this combination
      the patient's psychotic symptoms disappeared. He was able to maintain the
      relationship with psychiatrist. During this therapy we observed good compliance,
      no more drug abuse and no relapse.

PMID- 24108183
TI  - [Antidepressant treatment associated hyponatremia -- case report].
AB  - Hyponatremia is a potential side-effect of antidepressants that was observed most
      frequently in connection with compounds acting on the serotonin system. Risk of
      hyponatremia was found to be higher in the elderly. Authors report a case of a 65
      year old male patient who was treated with venlafaxine-mirtazapine combination
      for recurrent depression. Severe hyponatremia, requiring intensive care, emerged
      in connection with the treatment. The authors emphasize the importance of the
      regular checking of serum sodium levels during antidepressant treatment,
      especially in elderly patients.

PMID- 24108185
TI  - Robust adjustment of sequence tag abundance.
AB  - MOTIVATION: The majority of next-generation sequencing technologies effectively
      sample small amounts of DNA or RNA that are amplified (i.e. copied) before
      sequencing. The amplification process is not perfect, leading to extreme bias in
      sequenced read counts. We present a novel procedure to account for amplification
      bias and demonstrate its effectiveness in mitigating gene length dependence when
      estimating true gene expression. RESULTS: We tested the proposed method on
      simulated and real data. Simulations indicated that our method captures true gene
      expression more effectively than classic censoring-based approaches and leads to
      power gains in differential expression testing, particularly for shorter genes
      with high transcription rates. We applied our method to an unreplicated
      Arabidopsis RNA-seq dataset resulting in disparate gene ontologies arising from
      gene set enrichment analyses. AVAILABILITY AND IMPLEMENTATION: R code to perform
      the RASTA procedures is freely available on the web at
      www.stat.purdue.edu/~doerge/.

PMID- 24108186
TI  - The semantic measures library and toolkit: fast computation of semantic
      similarity and relatedness using biomedical ontologies.
AB  - The semantic measures library and toolkit are robust open-source and easy to use
      software solutions dedicated to semantic measures. They can be used for large
      scale computations and analyses of semantic similarities between terms/concepts
      defined in terminologies and ontologies. The comparison of entities (e.g. genes)
      annotated by concepts is also supported. A large collection of measures is
      available. Not limited to a specific application context, the library and the
      toolkit can be used with various controlled vocabularies and ontology
      specifications (e.g. Open Biomedical Ontology, Resource Description Framework).
      The project targets both designers and practitioners of semantic measures
      providing a JAVA library, as well as a command-line tool that can be used on
      personal computers or computer clusters. AVAILABILITY AND IMPLEMENTATION:
      Downloads, documentation, tutorials, evaluation and support are available at
      http://www.semantic-measures-library.org.

PMID- 24108187
TI  - Erythropoietin signaling promotes oligodendrocyte development following prenatal
      systemic hypoxic-ischemic brain injury.
AB  - BACKGROUND: Brain injury from preterm birth causes white matter injury (WMI), and
      it leads to chronic neurological deficits including cerebral palsy, epilepsy,
      cognitive, and behavioral delay. Immature O4+ oligodendrocytes are particularly
      vulnerable to WMI. Understanding how the developing brain recovers after injury
      is essential to finding more effective therapeutic strategies. Erythropoietin
      (EPO) promotes neuronal recovery after injury; however, its role in enhancing
      oligodendroglial lineage recovery is unclear. Previously, we found that
      recombinant EPO (rEPO) treatment enhances myelin basic protein (MBP) expression
      and functional recovery in adult rats after prenatal transient systemic hypoxia
      ischemia (TSHI). We hypothesized that after injury, rEPO would enhance
      oligodendroglial lineage cell genesis, survival, maturation, and myelination.
      METHODS: In vitro assays were used to define how rEPO contributes to specific
      stages of oligodendrocyte development and recovery after TSHI. RESULTS: After
      prenatal TSHI injury, rEPO promotes genesis of oligodendrocyte progenitors from
      oligodendrospheres, survival of oligodendrocyte precursor cells (OPCs) and O4+
      immature oligodendrocytes, O4+ cell process extension, and MBP expression. rEPO
      did not alter OPC proliferation. CONCLUSION: Together, these studies demonstrate
      that EPO signaling promotes critical stages of oligodendroglial lineage
      development and recovery after prenatal TSHI injury. EPO treatment may be
      beneficial to preterm and other infant patient populations with developmental
      brain injury hallmarked by WMI.

PMID- 24108188
TI  - Tracking donor RBC survival in premature infants: agreement of multiple
      populations of biotin-labeled RBCs with Kidd antigen-mismatched RBCs.
AB  - BACKGROUND: Anemia, a common condition among critically ill premature infants, is
      affected by red blood cell (RBC) survival (RCS). We hypothesized that transfused
      allogeneic Kidd antigen-mismatched RBCs would demonstrate the same concurrent RCS
      tracking as RBCs multilabeled at separate, discrete low densities with biotin
      (BioRBCs). METHODS: Allogeneic RBCs from adult donors were labeled at four biotin
      densities, mixed, and transfused into 17 anemic premature infants. Nine of the
      donors and neonates were Kidd antigen mismatched. Serial posttransfusion blood
      samples were assayed for up to 8 wk by flow cytometry to track the survival of
      the proportions of Kidd antigen-mismatched and Kidd antigen-biotinylated RBCs.
      RESULTS: Using linear mixed modeling to compare results, RCS of the three lowest
      BioRBC densities was similar to RCS by Kidd antigen mismatch and to one another.
      RCS of RBCs labeled at the highest BioRBC density was shortened. CONCLUSION: RCS
      of different populations of RBCs can be tracked concurrently and reliably using
      the three lowest BioRBC densities. Although comparable RCS results can be
      achieved using Kidd antigen mismatches, BioRBCs are preferred for investigating
      neonatal anemia because biotin labeling of both allogeneic and autologous RBCs is
      possible.

PMID- 24108190
TI  - Dual-templating synthesis of three-dimensionally ordered macroporous
      La(0.6)Sr(0.4)MnO3-supported Ag nanoparticles: controllable alignments and super
      performance for the catalytic combustion of methane.
AB  - Highly dispersed Ag nanoparticles supported on high-surface-area 3DOM
      La0.6Sr0.4MnO3 were successfully generated via the dimethoxytetraethylene glycol
      assisted gas bubbling reduction route. The macroporous materials showed super
      catalytic performance for methane combustion. 

PMID- 24108189
TI  - Structures and reaction mechanisms of the two related enzymes, PurN and PurU.
AB  - The crystal structures of glycinamide ribonucleotide transformylases (PurNs) from
      Aquifex aeolicus (Aa), Geobacillus kaustophilus (Gk) and Symbiobacterium toebii
      (St), and of formyltetrahydrofolate hydrolase (PurU) from Thermus thermophilus
      (Tt) were determined. The monomer structures of the determined PurN and PurU were
      very similar to the known structure of PurN, but oligomeric states were
      different; AaPurN and StPurN formed dimers, GkPurN formed monomer and PurU formed
      tetramer in the crystals. PurU had a regulatory ACT domain in its N-terminal
      side. So far several structures of PurUs have been determined, yet, the
      mechanisms of the catalysis and the regulation of PurU have not been elucidated.
      We, therefore, modelled ligand-bound structures of PurN and PurU, and performed
      molecular dynamics simulations to elucidate the reaction mechanisms. The
      evolutionary relationship of the two enzymes is discussed based on the
      comparisons of the structures and the catalytic mechanisms. 

PMID- 24108191
TI  - Longitudinal change in the use of services in autism spectrum disorder:
      understanding the role of child characteristics, family demographics, and parent
      cognitions.
AB  - The aim of this study was to identify child characteristics, family demographics,
      and parent cognitions that may affect access to early intervention, special
      education, and related services. The sample included 70 families of young
      children with autism spectrum disorders. All parents were enrolled in a short
      education program, providing them with basic information and resources on
      advocating for a young child with autism spectrum disorders (Parent Advocacy
      Coaching). Longitudinal change in children's intervention program in the
      community was evaluated over a period of about 27 months, starting 12 months
      prior to enrollment in Parent Advocacy Coaching. Results revealed large
      individual differences in the intensity of children's individual and school-based
      services. Despite this variability, only two child characteristics (age, gender)
      emerged as independent predictors. In contrast, the intensity of children's
      intervention programs was independently predicted by a broad range of demographic
      characteristics, including parental education, child ethnicity and race, and
      family composition. Finally, even after child characteristics and family
      demographics were statistically controlled, results revealed associations between
      specific parental cognitions (parenting efficacy, understanding of child
      development) and the subsequent rate of change in the intensity of children's
      intervention programs. Implications for improving educational programs that aim
      to enhance parent advocacy are discussed. 

PMID- 24108192
TI  - Predicting treatment success in social skills training for adolescents with
      autism spectrum disorders: the UCLA Program for the Education and Enrichment of
      Relational Skills.
AB  - This study seeks to examine the predictors of positive social skills outcomes
      from the University of California, Los Angeles Program for the Education and
      Enrichment of Relational Skills, an evidence-based parent-assisted social skills
      program for high-functioning middle school and high school adolescents with
      autism spectrum disorders. The results revealed that adolescents with higher
      parent-reported baseline social skills and lower self-reported perceived social
      functioning demonstrated greater improvement in social skills following the
      intervention. 

PMID- 24108193
TI  - Impact of genetic and clinical factors on dose requirements and quality of
      anticoagulation therapy in Polish patients receiving acenocoumarol: dosing
      calculation algorithm.
AB  - BACKGROUND: Despite the recent emergence of new oral anticoagulants, vitamin K
      antagonists remain the primary therapy in patients with atrial fibrillation and
      the only therapy licensed for use in patients with artificial heart valves.
      OBJECTIVE: The aim of this study was (a) to assess the impact of clinical and
      genetic factors on acenocoumarol (AC) dose requirements and the percentage of
      time in therapeutic range (%TTR) and (b) to develop pharmacogenetic-guided AC
      dose calculation algorithm. MATERIALS AND METHODS: We included 235 outpatients of
      the Institute of Cardiology (Warsaw), mean age 69.3, 46.9% women, receiving AC
      for artificial heart valves and/or atrial fibrillation. A multiple linear
      regression analysis was performed using log-transformed effective AC dose as the
      dependent variable, and combining CYP2C9 and VKORC1 genotyping with other
      clinical factors as independent predictors. RESULTS: We identified factors that
      influenced the AC dose: CYP2C9 polymorphisms (P=0.004), VKORC1 polymorphisms
      (P<0.0001), age (P<0.0001), creatinine clearance lower than 40 ml/min (P=0.035),
      body mass (P=0.02), and dietary vitamin K intake (P=0.026). Clinical and genetic
      factors explained 49.0% of AC dose variability. We developed a dosing calculation
      algorithm that is, to the best of our knowledge, the first one to assess the
      effect of such clinical factors as creatinine clearance and dietary vitamin K
      intake on the AC dose. The clinical usefulness of the algorithm was assessed on
      separate validation group (n=50) with 70% accuracy. Dietary vitamin K intake
      higher than 200 mcg/day improved international normalized ratio control (%TTR
      73.3+/-17 vs. 67.7+/-18, respectively, P=0.04). CONCLUSION: Inclusion of a
      variety of genetic and clinical factors in the dosing calculation algorithm
      allows for precise AC dose estimation in most patients and thus improves the
      efficacy and safety of the therapy.

PMID- 24108194
TI  - Spinal cord stimulation and intrathecal baclofen therapy: combined
      neuromodulation for treatment of advanced complex regional pain syndrome.
AB  - OBJECTIVE: Spinal cord stimulation (SCS) is one of the widely used procedures for
      the treatment of complex regional pain syndrome (CRPS). However, complete pain
      relief is rarely achieved, and the SCS effect diminishes over time. Recently
      intrathecal baclofen (ITB) therapy is reported to be a modality for treating
      fixed dystonia related to CRPS. Other reports have suggested that ITB therapy can
      enhance the effect of SCS in patients with neuropathic pain. We report the
      effectiveness of combined SCS and ITB therapy, focusing on the role of ITB
      therapy as an adjunctive therapy for controlling symptoms of advanced CRPS.
      METHODS: Five affected extremities of 4 patients with CRPS (2 male; mean age,
      32.5 years) refractory to conservative treatment were evaluated retrospectively.
      Three patients underwent SCS implantation first, with ITB pumps being implanted a
      few years later. Bolus ITB injection was administered under temporary
      percutaneous SCS in 1 patient. Pain intensity was evaluated using the visual
      analogue scale (VAS) before and after ITB administration. RESULTS: Pain relief of
      more than 50% was observed in the upper extremity of 1 patient and one of more
      than 30% was observed in 2 patients. The mean pain reduction rate in all 4
      patients was 28.9% before and 43.8% after treatment. All patients, including
      those without any improvements in VAS score, showed decreased postural
      abnormalities after combined SCS and ITB therapy. Improvement in postural
      abnormalities, such as fixed dystonia or paroxysmal tremor-like movements,
      resulted in overall pain relief by reducing pain fluctuations. CONCLUSIONS:
      Combined SCS and ITB neuromodulation decreases pain intensity in refractory CRPS
      cases or improves associated abnormal dystonic posture and movement disorders and
      reduces pain fluctuations.

PMID- 24108195
TI  - Theoretical investigation of the coupling between hydrogen atoms transfer and
      stacking interaction in guanine-cytosine dimers.
AB  - The effect of the stacking interaction on some properties of the guanine-cytosine
      (G-C) base pair has been studied. In particular, the strength of the hydrogen
      bonds, the mechanism of hydrogen transfer and the charge redistribution intra-
      and inter-base pair have been analyzed in the three canonical dimers. The
      inclusion of both the stacking interaction and of the hydrogen bond interaction
      between the bases allows us to study both the local and the long-range phenomena
      of DNA. The comparison of these results with those of the G-C monomeric system
      supports the idea that the variations of these properties depend from the exact
      dimer considered and are different for one or another hydrogen bond. Also the
      different mechanisms of two hydrogen transfer (step to step and concerted) can be
      modified by the stacking interaction between the base pairs. The comparison with
      previous data shows that some generalizations found in literature must be
      analyzed in detail. 

PMID- 24108197
TI  - Preclinical evaluation of gastrin derivatives labelled with 111In:
      radiolabelling, affinity profile and pharmacokinetics in rats.
AB  - BACKGROUND: Cholecystokinin receptor subtype 2 (CCK-2) is overexpressed in
      various tumours like medullary thyroid carcinomas and small cell lung cancer.
      Radiolabelled peptides that bind with high affinity and specificity to CCK-2
      receptors, thus hold great potential for visualizing such tumours. METHODS: We
      compared four 111In labelled gastrin analogues, called minigastrins (MG), namely
      MG11, MG45, MG47 and MG48 linked to metal chelating DOTA in preclinical
      experiments. The radiolabelled peptides were tested for peptide binding in CCK-2
      receptor-bearing cell line AR42J and for their pharmacokinetics in normal rats.
      RESULTS: The experiments suggest that all gastrin analogues had similar and
      relatively rapid internalization into AR42J cells. Binding to CCK-2 receptors in
      AR42J cells was saturable for all agents but there were some differences in
      receptor affinity. This biodistribution study in rats showed a rapid decrease in
      blood radioactivity, predominantly renal clearance and saturable uptake of the
      radiopharmaceutical and/or its metabolites in the CCK-2 receptor-positive
      stomach. Higher kidney accumulation of radioactivity was only found for 111In
      DOTA-minigastrin 48. CONCLUSIONS: The data suggest that the 111In-DOTA
      minigastrin analogues studied are promising candidates for the scintigraphy of
      CCK-2 receptor-expressing tumours; 111In-DOTA-MG47 and 111In-DOTA-MG11 are the
      most promising.

PMID- 24108196
TI  - Transvaginal/transumbilical hybrid--NOTES--versus 3-trocar needlescopic
      cholecystectomy: short-term results of a randomized clinical trial.
AB  - OBJECTIVE: For cholecystectomy, both the needlescopic cholecystectomy (NC) 3
      trocar technique using 2 to 3 mm trocars and the umbilical-assisted transvaginal
      cholecystectomy (TVC) technique have found their way into clinical routine. This
      study compares these 2 techniques in female patients who are in need of an
      elective cholecystectomy. BACKGROUND: Natural orifice transluminal endoscopic
      surgery (NOTES) is a surgical concept permitting scarless intra-abdominal
      operations through natural orifices, such as the vagina. Because of the lack of
      an adequately powered trial, we designed this first randomized controlled study
      for the comparison of TVC and NC. METHODS: This prospective, randomized,
      nonblinded, single-center trial evaluates the safety and effectiveness of TVC
      (intervention), compared with NC (control) in female patients with symptomatic
      cholecystolithiasis. The primary endpoint was intensity of pain until the morning
      of postoperative day (POD) 2. Secondary outcomes were among others intra- and
      postoperative complications, procedural time, amount of analgesics used, pain
      intensity until POD 10, duration of hospital stay, satisfaction with the
      aesthetic result, and quality of life on POD 10 as quantified with the Eypasch
      Gastrointestinal Quality of Life Index (GIQLI). RESULTS: Between February 2010
      and June 2012, 40 patients were randomly assigned to the interventional or
      control group. All patients completed follow-up. Procedural time, length of
      postoperative hospital stay, and the rate of intra- and postoperative
      complications were similar in the 2 groups. However, significant advantages were
      found for the transvaginal access regarding pain until POD 2, but also until POD
      10 (P = 0.043 vs P = 0.010) despite significantly less use of peripheral
      analgesics (P = 0.019). In the TVC group, patients were significantly more
      satisfied with the aesthetic result (P < 0.001) and had a significantly better
      GIQLI (P = 0.028). CONCLUSIONS: Although comparable in terms of safety, TVC
      caused less pain, increased satisfaction with the aesthetic result, and improved
      postoperative quality of life in the short term.

PMID- 24108198
TI  - Relationship between reactive oxygen species production in human semen and sperm
      DNA damage assessed by Sperm Chromatin Structure Assay.
AB  - AIM: The aim of this prospective study was to find possible relationship between
      ROS production measured by chemiluminescence and flow cytometry in human semen
      and sperm DNA damage estimated by Sperm Chromatin Structure Assay. METHODS: Study
      included 39 men from infertile couples and 23 fertile volunteers who served as a
      control group. Aliquot of neat semen was used for ROS detection by
      chemiluminescence. Aliquot of sperm suspension in phosphate buffered saline was
      used for the detection of ROS by flow cytometry. Another aliquot of sperm
      suspension was used for SCSA to measure DNA fragmentation index and High DNA
      stainability. RESULTS: DNA fragmentation index correlated negatively with sperm
      morphology and motility. High DNA stainability correlated positively with ROS
      production and negatively with sperm morphology and concentration. Although there
      were similar trends of rising DNA fragmentation index and ROS production among
      the three groups of men, the relationship did not reach statistical significance.
      CONCLUSIONS: Higher values of DNA fragmentation index and high DNA stainability
      may also reflect developmental and/or environmental problems and not only
      oxidative stress.

PMID- 24108199
TI  - High amounts of broccoli in pasta-like products: nutritional evaluation and
      sensory acceptability.
AB  - Pasta and noodles were enriched with concentrations of broccoli powder (BP) up to
      30% (v/v). To ensure the benefits from the broccoli nutrients, their leakage
      during cooking should be prevented. Such leakage is determined by the
      microstructure. In a previous study we have shown that the microstructure can
      change dramatically in such broccoli-enriched products. In this article we
      investigated the amount of nutrients retained within the product. As a
      representative of nutrients we have chosen glucosinolates (GLs). Therefore, we
      have investigated the concentration of these phytochemicals in dried and cooked
      pasta and noodles. We have found that glucosinolates present in the pasta and
      noodles increase linearly with the volume fraction of BP up to 20%. At 30% BP the
      retained amount of GLs was equal to that of 20% BP and did not increase further.
      Therefore incorporation of 30% BP does not lead to additional health benefits
      over incorporation of 20% BP. We conclude that the nutritional function of our
      pasta-like products can be improved by enrichment up to 20% broccoli. This value
      is much higher than that found in common commercial products (which is a few
      percent). In this article we also briefly address the sensory acceptability of
      such products. Up to 20% broccoli the products turned out to remain acceptable.
      Combining this with our results on texture analysis we conclude that the GLs
      release, sensory acceptability and textural properties are related via the
      microstructure. 

PMID- 24108200
TI  - Chronic myelogenous leukaemia with persistent neutrophilia, eosinophilia and
      basophilia in a cat.
AB  - Chronic myelogenous leukaemia was diagnosed in a 7-year-old male neutered
      domestic shorthair cat. Leukocytosis (74,900/ul)--mature neutrophilia,
      eosinophilia and basophilia--was observed. Bone marrow aspiration revealed
      hypercellularity with proliferation of cells of myeloid lineage. An underlying
      condition leading to leukocytosis was not identified. The severe leukocytosis did
      not respond to antibiotic therapy. Based on these findings, chronic myelogenous
      leukaemia was diagnosed. Because of the absence of clinical signs, the cat was
      monitored without treatment until 7 months after diagnosis, when it developed
      pruritic skin lesions. Pruritus was controlled with oral prednisolone. Forty-two
      months after diagnosis, the cat developed nasal lymphoma, which was treated with
      radiation therapy, resulting in complete remission. The cat was still in good
      physical condition 63 months after diagnosis, despite the persistence of marked
      neutrophilia, eosinophilia and basophilia.

PMID- 24108201
TI  - Tail vaccination in cats: a pilot study.
AB  - Feline injection site sarcomas affect 1-10 cats per every 10,000 vaccinated and
      are associated with high mortality. Radical resection may be curative, but is
      often associated with prolonged recovery, disfigurement and loss of function when
      tumors occur at currently recommended injection sites. The objective of this
      study was to assess alternatives to currently recommended vaccination sites in
      terms of preference by oncology practitioners, ease of injection and serological
      responses. Surgical, radiation and medical oncology practitioners were surveyed
      regarding their preference for vaccination sites based on the ease of tumor
      resection. A six-point Likert scale was used to measure each cat's behavioral
      reaction to vaccination when injected subcutaneously in the distal hind limb or
      the distal tail. Serum collected before and 1-2 months after vaccination was
      tested for antibody titers against feline panleukopenia virus (FPV) and rabies
      virus (RV). The preferred sites for vaccination by 94 oncology practitioners were
      below the stifle (41%) and the tail (30%). There were no significant differences
      in the cats' behavioral reaction to vaccination below the stifle (n = 31) and in
      the distal tail (n = 29). Of the cats seronegative for FPV at the time of
      vaccination, 100% developed protective antibody titers (>=40) against FPV 1-2
      months following vaccination. For cats seronegative for RV, all but one cat (tail
      vaccine) developed acceptable antibody titers (>=0.5 IU/ml) against RV. Tail
      vaccination was well tolerated and elicited similar serological responses to
      vaccination in the distal limbs. 

PMID- 24108202
TI  - Pericardial lymphoma in seven cats.
AB  - A presumed primary pericardial lymphoma was diagnosed in seven cats. Clinical
      findings at presentation included poor body condition, dehydration and dyspnoea.
      Thoracic diagnostic imaging was performed in six cases and revealed pleural
      effusion and a diffuse thickening of the pericardium. A cytological diagnosis of
      lymphoma was obtained in six cases; in four cases the diagnosis was confirmed at
      necropsy. Immunophenotyping was performed in six cases: three cases were
      classified as T-cell and three as B-cell lymphoma. Four cats did not receive any
      treatment. One cat received only prednisone and two cats received chemotherapy.
      Six cats lived 7-11 days, except for one cat that received a multi-drug
      chemotherapy protocol and was still alive at the time of writing (750 days after
      diagnosis). Primary pericardial lymphoma is a rare extranodal feline lymphoma
      that has never been described previously. 

PMID- 24108203
TI  - Evaluating the inappropriateness of repeated laboratory testing in a teaching
      hospital of South Italy.

PMID- 24108204
TI  - Urinary neutrophil gelatinase-associated lipocalin (NGAL) excretion increases in
      normal pregnancy but not in preeclampsia.
AB  - BACKGROUND: Neutrophil gelatinase-associated lipocalin (NGAL) serum values have
      been shown to increase in preeclampsia. The goal of the present study was to
      evaluate changes in urinary NGAL concentrations during uncomplicated pregnancy
      and in cases of preeclampsia and hypertension. METHODS: Fifty-one pregnant women
      who developed preeclampsia and 28 diagnosed with essential or gestational
      hypertension were investigated for urinary NGAL concentrations during pregnancy.
      As controls, 100 healthy pregnant women with uncomplicated singleton pregnancies
      were randomly selected. Urinary NGAL as well as urinary creatinine and albumin
      were measured by a standardized clinical chemistry platform (ARCHITECT(r); Abbott
      Diagnostics, Abbott Park, IL, USA). RESULTS: Urinary NGAL concentrations
      increased during pregnancy in healthy pregnant women, whereas this increase was
      not detected in preeclampsia. In order to correct for diuresis, spot urine
      concentrations were also determined as NGAL/creatinine ratio. NGAL/creatinine
      ratio in pregnancy week 36-38 was significantly lower in preeclampsia than in
      healthy pregnant women or pregnant women with hypertension. NGAL urinary
      concentrations did not correlate with albumin concentration in urine.
      CONCLUSIONS: Urinary NGAL is not a valuable early biomarker for preeclampsia.

PMID- 24108205
TI  - Influence of urine volume on the assessment of intestinal permeability in
      affected children by multiple sugar probes.
AB  - BACKGROUND: In this study we have looked at the reliability of a multi-sugar test
      in a pediatric patient population and its accuracy at small urine volumes to
      evaluate intestinal permeability. METHODS: Out of 117 subjects enrolled, 31 were
      healthy and 86 were sick. A solution containing lactulose, rhamnose, sucrose, and
      sucralose was administered to subjects who were on fasting; the urine excreted
      during 5 h was collected and measured. Samples were analyzed by gas
      chromatography-tandem mass spectrometry and results were expressed as percentage
      of sugar recoveries and lactulose/rhamnose (L/R) ratio. RESULTS: The analyses
      showed a clear effect of low urinary volumes (<=240 mL) particularly affecting
      rhamnose excretion in healthy subjects and sucrose and sucralose recovery in
      diseased children. Despite the low rhamnose recovery, as lactulose is not
      similarly affected, the diagnostic reliability of L/R ratio is well preserved at
      low diuresis conditions. However, this ratio can be useful to discriminate acute
      conditions vs. clinical remissions only at high urine volumes. Data also suggest
      potential diagnostic applicability of sucrose and sucralose in children at high
      urine volumes. CONCLUSIONS: In conclusion, the multi-sugar test has a good
      predictivity in pediatric subjects but results must be carefully interpreted in
      the face of reduced diuresis.

PMID- 24108206
TI  - Absorptive chemistry based extraction for LC-MS/MS analysis of small molecule
      analytes from biological fluids - an application for 25-hydroxyvitamin D.
AB  - BACKGROUND: Already available sample preparation technologies for liquid
      chromatography-tandem mass spectrometry have substantial shortcomings with
      respect to automation. A novel approach is based on gel-like polymeric material
      with defined absorption chemistry, which is immobilized in micro-plate wells. It
      is referred to as Tecan Immobilized Coating ExtractionTM (TICETM) technology and
      it enables easy automation on liquid handling systems. We aimed to study the
      performance of Tecan AC Extraction PlateTM based on this principle by addressing
      25-hydroxyvitamin D (25OHD) as an exemplary analyte. METHODS: A protocol for
      extraction of 25OHD from serum samples based on TICETM technology was implemented
      on a robotic liquid handling system Freedom EVO(r) (Tecan). An isotope-dilution
      ultra-performance liquid chromatography-tandem mass spectrometry method was used
      for quantification. Performance was tested according to a comprehensive protocol.
      RESULTS: Linearity was found over a range from 4.3 to 65.8 ng/mL for 25OHD3. The
      coefficients of variation for the intra-day and inter-day precision were <6% and
      accuracy ranged between 96.9% and 99.8% for 25OHD3. Recovery was 84% and
      efficient control of matrix effects was verified. High sample throughput could be
      observed with 96 samples prepared in <60 min. Close agreement of results was
      found for clinical samples analyzed with a second tandem mass spectrometry method
      based on protein precipitation and two-dimensional ultra-performance liquid
      chromatography for sample preparation (r=0.988, n=73). CONCLUSIONS: The new
      TICETM technology was found to be a useful process for sample preparation in
      clinical mass spectrometry. Full automation suited for routine analysis was
      achieved.

PMID- 24108207
TI  - Could kidney glomerular filtration impairment represent the "Achilles heel" of
      HE4 serum marker? A possible further implication.

PMID- 24108208
TI  - Plasma endothelial cell-specific molecule-1 (ESM-1) in management of community
      acquired pneumonia.
AB  - BACKGROUND: Endothelial cell-specific molecule (ESM)-1 is a soluble proteoglycan
      expressed by the vascular endothelium and which also circulates in the
      bloodstream. Inflammatory cytokines and proangiogenic growth factors increase its
      expression, and increased serum levels are found in immunocompetent patients with
      sepsis. The aim of this study was to investigate differential changes in plasma
      levels of ESM-1 before and after antibiotic treatment in hospitalized adult
      patients with community-acquired pneumonia (CAP). METHODS: Plasma ESM-1 levels
      were measured in 82 adult patients with CAP and 82 healthy controls using a
      commercial enzyme-linked immunosorbent assay (ELISA). Upon initial
      hospitalization, Acute Physiology and Chronic Health Evaluation II (APACHE II),
      CURB-65, and Pneumonia Severity Index (PSI) scores were determined to assess CAP
      severity in these patients. RESULTS: Results showed a decline in the number of
      white blood cells (WBCs) and neutrophils, and decreases in the concentrations of
      C-reactive protein (CRP) and ESM-1 after antibiotic treatment. The plasma
      concentration of ESM-1, but not CRP or the WBC count, was correlated with the
      severity of CAP based on the PSI (r=0.554, p<0.001), CURB-65 (r=0.510, p<0.001),
      and APACHE II scores (r=0.447, p<0.001). CONCLUSIONS: Plasma levels of ESM-1 may
      be able to play a role in the diagnosis and clinical assessment of the severity
      of CAP, which could potentially guide the development of treatment strategies.

PMID- 24108209
TI  - Evaluation of 3-epi-25-hydroxyvitamin D3 cross-reactivity in the Roche Elecsys
      Vitamin D Total protein binding assay.
AB  - BACKGROUND: Presence of the 3-epi-25-hydroxyvitamin D3 [3-epi-25(OH)D3]
      metabolite affects accurate determination of 25(OH)D3 by most routine liquid
      chromatography-tandem mass spectrometry (LC-MS/MS) methods and to an unknown
      extent in present immuno- and protein binding assays. We studied 3-epi-25(OH)D3
      cross-reactivity in a competitive protein binding (CPB) assay (Roche Elecsys).
      METHODS: Neonatal samples, containing up to 58% of 3-epi-25(OH)D3 were used for
      measurement by the CPB assay and by an LC-MS/MS method separating 25(OH)D3 and 3
      epi-25(OH)D3. Analytical recovery was also studied by addition of exogenous 3-epi
      25(OH)D3. RESULTS: The CPB assay showed approximately 51% cross-reactivity to 3
      epi-25(OH)D3 at exogenous addition. In contrast, there was minimal 3-epi-25(OH)D3
      recognition by the CPB assay when present as the natural endogenous metabolite.
      CONCLUSIONS: The automated CPB assay displays minimal 3-epi-25(OH)D3 cross
      reactivity in samples containing significant concentrations of endogenous 3-epi
      25(OH)D3. Exogenous 3-epi-25(OH)D3 added to human serum or plasma seems to behave
      different from endogenous presence, and caution is warranted when using samples
      spiked with vitamin D metabolites for testing analytical specificity or external
      quality assurance in immuno- or protein binding assays.

PMID- 24108210
TI  - Inflammatory bowel diseases: from pathogenesis to laboratory testing.
AB  - Inflammatory bowel diseases (IBDs), which comprise the two major clinical
      subtypes, Crohn's disease and ulcerative colitis, incur high morbidity and
      potential mortality. The present study reviews data on the pathogenesis and
      diagnosis of IBDs. The pathogenesis depends on complex interactions between
      susceptibility genes, environmental factors, and innate and adaptive immunity,
      the understanding of which is crucial to discovering novel laboratory biomarkers.
      Traditional laboratory tests for the diagnosis, prognosis and assessment of
      disease activity of IBDs are reported on, and the biochemical properties, pre
      analytical and analytical aspects and clinical utility of the fecal markers
      lactoferrin and calprotectin are described. DNA testing and established (ASCA and
      pANCA) and emerging (ACCA, ALCA, AMCA, OmpC) serum markers are described; a
      further aspect to be addressed is the clinical use of pharmacogenetics for the
      treatment of IBDs.

PMID- 24108211
TI  - Critical role of RAGE in lung physiology and tumorigenesis: a potential target of
      therapeutic intervention?
AB  - Lung cancer is one of the most common malignancies in the world and one of the
      leading causes of death from cancer. In the search for molecules that may be
      involved in lung tumor induction and progression, the receptor of advanced
      glycation end products (RAGE) comes across as a critical regulator of lung
      physiology. RAGE is a multiligand receptor that presents a differential
      expression pattern in lung epithelial cells compared to other cell types being
      gradually increased from fetal to birth and adult life. Under stress conditions,
      RAGE expression and activation are rapidly elevated resulting in chronic
      inflammation, which, in turn, in many instances, promotes epithelial cell
      malignant transformation. RAGE overexpression in normal lung alveolar type I
      epithelial cells is followed by rapid downregulation upon malignant
      transformation, being associated with increased aggressiveness. This is a
      striking paradox, since in every other cell type the pattern of RAGE expression
      follows the opposite direction, suggesting the involvement of RAGE in the well
      functioning of lung cells. Additionally, RAGE has been attributed with the role
      of adhesion molecule, since it can stabilize mature alveolar epithelial cells to
      their substrate (basal lamina) by interacting electrostatically with other
      molecules. However, the reduction of RAGE observed in lung tumorigenesis
      interrupts cell-to-cell and cell-to-substrate communication, which is a critical
      step for cancer cell induction, progression and migration. This review addresses
      the differential properties of RAGE in lung physiology and carcinogenesis,
      providing evidence of therapeutic possibilities.

PMID- 24108212
TI  - Evolution of bacterial-like phosphoprotein phosphatases in photosynthetic
      eukaryotes features ancestral mitochondrial or archaeal origin and possible
      lateral gene transfer.
AB  - Protein phosphorylation is a reversible regulatory process catalyzed by the
      opposing reactions of protein kinases and phosphatases, which are central to the
      proper functioning of the cell. Dysfunction of members in either the protein
      kinase or phosphatase family can have wide-ranging deleterious effects in both
      metazoans and plants alike. Previously, three bacterial-like phosphoprotein
      phosphatase classes were uncovered in eukaryotes and named according to the
      bacterial sequences with which they have the greatest similarity: Shewanella-like
      (SLP), Rhizobiales-like (RLPH), and ApaH-like (ALPH) phosphatases. Utilizing the
      wealth of data resulting from recently sequenced complete eukaryotic genomes, we
      conducted database searching by hidden Markov models, multiple sequence
      alignment, and phylogenetic tree inference with Bayesian and maximum likelihood
      methods to elucidate the pattern of evolution of eukaryotic bacterial-like
      phosphoprotein phosphatase sequences, which are predominantly distributed in
      photosynthetic eukaryotes. We uncovered a pattern of ancestral mitochondrial (SLP
      and RLPH) or archaeal (ALPH) gene entry into eukaryotes, supplemented by possible
      instances of lateral gene transfer between bacteria and eukaryotes. In addition
      to the previously known green algal and plant SLP1 and SLP2 protein forms, a more
      ancestral third form (SLP3) was found in green algae. Data from in silico
      subcellular localization predictions revealed class-specific differences in
      plants likely to result in distinct functions, and for SLP sequences, distinctive
      and possibly functionally significant differences between plants and
      nonphotosynthetic eukaryotes. Conserved carboxyl-terminal sequence motifs with
      class-specific patterns of residue substitutions, most prominent in
      photosynthetic organisms, raise the possibility of complex interactions with
      regulatory proteins. 

PMID- 24108214
TI  - Fabrication of a boron nitride-gold nanocluster composite and its versatile
      application for immunoassays.
AB  - A multifunctional boron nitride-gold nanocluster composite was fabricated using
      poly-diallyldimethylammonium chloride as a stabilizer and a linker. The as
      fabricated composite could be used as a fluorescent or an electrochemical label
      for immunosensing in the sensitive detection of interleukin-6. 

PMID- 24108213
TI  - A pair of tabersonine 16-hydroxylases initiates the synthesis of vindoline in an
      organ-dependent manner in Catharanthus roseus.
AB  - Hydroxylation of tabersonine at the C-16 position, catalyzed by tabersonine 16
      hydroxylase (T16H), initiates the synthesis of vindoline that constitutes the
      main alkaloid accumulated in leaves of Catharanthus roseus. Over the last decade,
      this reaction has been associated with CYP71D12 cloned from undifferentiated C.
      roseus cells. In this study, we isolated a second cytochrome P450 (CYP71D351)
      displaying T16H activity. Biochemical characterization demonstrated that CYP71D12
      and CYP71D351 both exhibit high affinity for tabersonine and narrow substrate
      specificity, making of T16H, to our knowledge, the first alkaloid biosynthetic
      enzyme displaying two isoforms encoded by distinct genes characterized to date in
      C. roseus. However, both genes dramatically diverge in transcript distribution in
      planta. While CYP71D12 (T16H1) expression is restricted to flowers and
      undifferentiated cells, the CYP71D351 (T16H2) expression profile is similar to
      the other vindoline biosynthetic genes reaching a maximum in young leaves.
      Moreover, transcript localization by carborundum abrasion and RNA in situ
      hybridization demonstrated that CYP71D351 messenger RNAs are specifically located
      to leaf epidermis, which also hosts the next step of vindoline biosynthesis.
      Comparison of high- and low-vindoline-accumulating C. roseus cultivars also
      highlights the direct correlation between CYP71D351 transcript and vindoline
      levels. In addition, CYP71D351 down-regulation mediated by virus-induced gene
      silencing reduces vindoline accumulation in leaves and redirects the biosynthetic
      flux toward the production of unmodified alkaloids at the C-16 position. All
      these data demonstrate that tabersonine 16-hydroxylation is orchestrated in an
      organ-dependent manner by two genes including CYP71D351, which encodes the
      specific T16H isoform acting in the foliar vindoline biosynthesis. 

PMID- 24108215
TI  - Hyperbolic spin vortices and textures in exciton-polariton condensates.
AB  - From cosmology to the microscopic scales of the quantum world, the study of
      topological excitations is essential for the understanding of phase conformation
      and phase transitions. Quantum fluids are convenient systems to investigate
      topological entities because well-established techniques are available for their
      preparation, control and measurement. Across a phase transition, a system
      dramatically changes its properties because of the spontaneous breaking of
      certain continuous symmetries, leading to generation of topological defects. In
      particular, attention is given to entities that involve both spin and phase
      topologies. Exciton-polariton condensates are quantum fluids combining coherence
      and spin properties that, thanks to their light-matter nature, bring the
      advantage of direct optical access to the condensate order parameter. Here we
      report on the spontaneous occurrence of hyperbolic spin vortices in polariton
      condensates, by directly imaging both their phase and spin structure, and observe
      the associated spatial polarization patterns, spin textures that arise in the
      condensate. 

PMID- 24108216
TI  - Implementing conventional Zamorano Dujovny frames versus individually
      manufactured microTargeting platforms--a comparative study on deep brain
      stimulation in Parkinson patients.
AB  - BACKGROUND AND OBJECTIVES: Individually manufactured microTargetingTM platforms
      (MT) provide a novel generation of stereotactic systems based on preoperatively
      implanted bone markers and screws. The feasibility and reliability of these
      frames were evaluated for bilateral deep brain stimulation (DBS) in patients with
      idiopathic Parkinson's disease (IPD). Surgical and clinical results were compared
      to conventional Zamorano Dujovny frames (ZD) in this prospective study. MATERIALS
      AND METHODS: Twenty-six IPD patients undergoing surgery for DBS were divided into
      2 groups. In group I, electrode implantation was accomplished using conventional
      ZD. Group II underwent electrode implantation using MT. Microrecording and
      macrostimulation were performed and surgery time was measured. The clinical
      outcome was determined using the Unified Parkinson's Disease Rating Scale Part
      III (UPDRS III) and L-dopa-equivalent doses for a 12-month follow-up
      postoperatively. RESULTS: Clinical evaluation confirmed comparable outcomes for
      both targeting procedures and electrode positioning. Surgical time was lower in
      group II than in group I. Significant improvements were determined for both
      groups in UPDRS III and L-dopa-equivalent dose. CONCLUSIONS: Both systems allow
      for reliable and safe neurosurgical procedures, yielding comparable clinical
      results. MT improved handling and automatic adjustment of frame coordinates.
      Surgery time was reduced markedly compared to conventional frames.

PMID- 24108217
TI  - Drugs associated with teratogenic mechanisms. Part II: a literature review of the
      evidence on human risks.
AB  - STUDY QUESTION: What is the current state of knowledge on the human risks of
      drugs suspected to be associated with teratogenic mechanisms? SUMMARY ANSWER:
      Evidence for the presence or absence of human risks of birth defects is scarce or
      non-existent for the majority of drugs associated with teratogenic mechanisms.
      WHAT IS KNOWN ALREADY: Medical drugs suspected to be associated with teratogenic
      mechanisms are dispensed to a significant proportion of women in the first
      trimester of pregnancy. However, an overview of the current state of knowledge on
      the human teratogenic effects of these drugs is lacking. STUDY DESIGN, SIZE,
      DURATION: We performed an extensive literature review of studies in the English
      language which examined the associations between selected drugs and specific
      birth defects. The literature was identified from MEDLINE and EMBASE from
      database inception (January 1946 and January 1974, respectively) through December
      2012 using 287 terms for the drugs of interest. We only included studies if they
      specified birth defect subtypes and, specifically for cohort studies, involved
      live born infants. PARTICIPANTS/MATERIALS, SETTING, METHODS: Of 14 406
      potentially relevant articles, 556 full-text articles were assessed for
      eligibility and 250 met the inclusion criteria. The studies included were divided
      into four categories according to their design to increase the validity of our
      study. MAIN RESULTS AND THE ROLE OF CHANCE: Epidemiologic studies assessing
      teratogenic risks were identified for less than half of the drugs included in the
      review. A substantial variation in study design and data collection methods was
      observed. When the data collection method is of questionable validity, study
      quality may be affected considerably. For only 15 drugs of interest, birth
      defects were assessed in at least 1000 infants in cohort studies, and 13 of these
      were associated with one or more specific birth defects. The majority of
      associations observed in case-control studies are as yet unconfirmed. For most
      drugs and drug groups, however, the numbers of exposed infants studied were too
      small to draw any conclusions regarding their human teratogenic risks.
      LIMITATIONS, REASONS FOR CAUTION: The validity of our review is limited by the
      validity and reporting of the studies from which the data were extracted. Some
      relevant studies might have been missed owing to the exclusion of articles not in
      the English language and publication bias. WIDER IMPLICATIONS OF THE FINDINGS: It
      is a cause of concern that the drugs most often dispensed in the first trimester
      of pregnancy are not necessarily the drugs for which teratogenic risks have been
      studied. Future studies should focus on those drugs that are most commonly used
      during pregnancy and for which the teratogenic risks are unknown, such as iron
      preparations, serotonin receptor agonists or antagonists, drugs used in fertility
      treatment, dihydrofolate reductase inhibitors. STUDY FUNDING/COMPETING
      INTEREST(S): Marleen van Gelder was supported by the Netherlands Organisation for
      Scientific Research/NWO (grant no. 021.001.008). No competing interests are
      declared. TRIAL REGISTRATION NUMBER: N/A.

PMID- 24108218
TI  - Birthweight and placental weight; do changes in culture media used for IVF
      matter? Comparisons with spontaneous pregnancies in the corresponding time
      periods.
AB  - STUDY QUESTION: Have changes in culture media used for IVF resulted in changes in
      offspring birthweight or placental weight that differed from the trends in
      offspring from spontaneous conceptions during the corresponding time periods?
      SUMMARY ANSWER: Changes in culture media used for IVF were associated with
      significant differences in offspring birthweight and in placental weight to
      birthweight ratio when compared with the trend in offspring from spontaneous
      conceptions during the time periods. WHAT IS KNOWN ALREADY: The effect of culture
      media used for IVF on offspring birthweight has varied between studies. There is
      a large variation in birthweight between newborns, and birthweight may vary
      across populations and over time. Such variations may therefore have influenced
      previous results. STUDY DESIGN, SIZE, DURATION: We included all singleton births
      from IVF at one treatment center in Norway during the years 1999-2011(n = 2435)
      and all singleton births from spontaneous conceptions in Norway during the same
      years (n = 698 359). PARTICIPANTS/MATERIALS, SETTING, METHODS: Three different
      media were used for embryo culture; Medicult Universal IVF (1999 through 2007, n
      = 1584), Medicult ISM1 (2008 until 20 September 2009, n = 402) and Vitrolife G-1
      PLUS (21 September 2009 through 2011, n = 449). We estimated mean birthweight and
      placental weight in IVF pregnancies by culture media. We also estimated mean
      weights in IVF and in spontaneous pregnancies by year of birth. Thereafter, we
      studied whether the changes in mean weights in IVF pregnancies differed from the
      changes in weight in spontaneous pregnancies in the periods corresponding to
      culture media changes by applying a grouped difference-in-difference analysis.
      Adjustments were made for parity, maternal age and gestational age at birth. MAIN
      RESULTS AND THE ROLE OF CHANCE: In singleton offspring from IVF the mean
      birthweight was 3447.6 g with Medicult Universal, 3351.7 g with Medicult ISM1 and
      3441.4 g with Vitrolife G-1 PLUS (P < 0.05). The corresponding mean placental
      weights were 684.1, 693.4 and 704.3 g (P < 0.05). In offspring from spontaneous
      conceptions the mean birthweight decreased (56.9 g) and the placental weight
      increased (9.3 g) during the study period. The adjusted difference in birthweight
      in offspring from IVF decreased with 35.0 g by the change from Medicult Universal
      to Medicult ISM1 (P = 0.16) and increased with 79.9 g by the change from Medicult
      ISM1 to Vitrolife G-1 PLUS (P = 0.01) when compared with changes in offspring
      after spontaneous conceptions, We also found a significant increase in placental
      weight in relation to birthweight by the change from Medicult ISM1 to Vitrolife G
      1 PLUS (P = 0.02). LIMITATIONS, REASONS FOR CAUTION: There may be underlying
      factors that have influenced both birthweight and the use of culture media in IVF
      pregnancies. Lack of adjustment for such possible factors may have biased our
      results. WIDER IMPLICATIONS OF THE FINDINGS: We found a significant effect of
      culture media used for IVF on birthweight and on placental weight in relation to
      birthweight. Also the population changes over time should encourage
      identification of factors in very early embryonic life that may influence
      birthweight and placental weight. STUDY FUNDING/COMPETING INTERESTS: We received
      funding from the South-Eastern Regional Health Authority in Norway for this study
      (2011136-2012). None of the authors has any conflicts of interest to declare.

PMID- 24108220
TI  - NaYF4 nanocrystals with TOPO ligands: synthesis-dependent structural and
      luminescent properties.
AB  - A comprehensive characterization of NaYF4 nanocrystals synthesized in
      trioctylphosphine oxide has been reported in order to present an effective method
      of monodisperse, small, hexagonal nanocrystal synthesis in a high boiling organic
      solvent via a co-thermolysis pathway. We observed the influence of temperature,
      Na/Y precursors ratio and time of the synthesis on the nanocrystals size, shape
      and crystal structure. For that purpose, we characterized the structure of as
      synthesized nanocrystals by X-ray diffraction and transmission electron
      microscopy. Moreover, all nanocrystals were doped with Eu(3+) ions, which were
      used as an optical crystal field probe. We applied photoluminescence, PL
      excitation and absorbance spectra to determine the influence of crystal symmetry,
      surface to volume ratio and ligands on the optical properties of doped Eu(3+)
      ions. It was found that trioctylphosphine oxide reduces the free-energy barrier
      and stimulates the NaYF4 crystallization in the hexagonal phase, even at
      relatively low temperature. A similar effect was observed when the excess of
      sodium trifluoroacetate precursors was used. Moreover, the presented nanocrystal
      evolution within synthesis time confirmed that at suitable conditions NaYF4
      crystallized in the hexagonal phase within less than 5 min. Optical spectroscopy
      investigations confirmed the high quality of small beta-NaYF4:Eu(3+)
      nanocrystals, which are promising candidates for e.g. optical markers in the
      visible wavelength range. 

PMID- 24108223
TI  - Bringing balance to institutional review board oversight in human subject
      research.

PMID- 24108222
TI  - Addition of platelet concentrate to dermo-epidermal skin graft in deep burn
      trauma reduces scarring and need for revision surgeries.
AB  - BACKGROUND: [corrected] Deep skin burn injuries, especially those on the face,
      hands, feet, genitalia and perineum represent significant therapeutic challenges.
      Autologous dermo-epidermal skin grafts (DESG) have become standard of care for
      treating deep burns. Additionally, human autologous thrombin activated autologous
      platelet concentrate (APC) has gained acceptance in the setting of wounds. While
      each of these interventions has been independently shown to accelerate healing,
      the combination of the two has never been evaluated. We hypothesized that the
      addition of platelets (source of growth factors and inhibitors necessary for
      tissue repair) to the DESG (source of progenitor cells and of tissue proteases
      necessary for spatial and temporal control of growth regulators released from
      platelets) would create the optimal environment for the reciprocal interaction of
      cells within the healing tissues. METHODS: We used clinical examination (digital
      photography), standardised scales for evaluating pain and scarring, in
      combination with blood perfusion (laser Doppler imaging), as well as molecular
      and laboratory analyses. RESULTS: We show for the first time that the combination
      of APC and DESG leads to earlier relief of pain, and decreased use of analgesics,
      antipruritics and orthotic devices. Most importantly, this treatment is
      associated with earlier discharges from hospital and significant cost savings.
      CONCLUSIONS: Our findings indicate that DESG engraftment is facilitated by the
      local addition of platelets and by systemic thrombocytosis. This local
      interaction leads to the physiological revascularization at 1-3 months. We
      observed significant elevation of circulating platelets in early stages of
      engraftment (1-7 days), which normalized over the subsequent 7 and 90 days.

PMID- 24108225
TI  - Preventing obesity and promoting cardiometabolic health: the promise and
      potential of policies and the Affordable Care Act.

PMID- 24108227
TI  - Abuse as a gendered risk factor for cardiovascular disease: a conceptual model.
AB  - BACKGROUND: Cardiovascular disease (CVD) is one of the most serious health
      challenges facing women today. Investigations into CVD risk factors specific to
      women have focused primarily on sex-based differences, with little attention paid
      to gender-based influences. Abuse, such as child abuse, intimate partner
      violence, and sexual assault, is a serious gendered issue affecting one quarter
      to one-half of all women within their lifetime. Despite beginning evidence that
      abuse may increase CVD risk in women, the biological, behavioral, and
      psychological pathways linking abuse to CVD have received little attention from
      researchers and clinicians. PURPOSE: The aim of this study was to propose a
      conceptual model that delineates the pathways by which abuse may increase CVD
      risk among women. Within the model, lifetime abuse is positioned as a chronic
      stressor affecting CVD risk through direct and indirect pathways. Directly, abuse
      experiences can cause long-term biophysical changes within the body, which
      increase the risk of CVD. Indirectly, smoking and overeating, known CVD risk
      behaviors, are common coping strategies in response to abuse. In addition, women
      with abuse histories frequently report depressive symptoms, which can persist for
      years after the abusive experience. Depressive symptoms are a known predictor of
      CVD and can potentiate CVD risk behaviors. Therefore, depressive symptoms are
      proposed as a mediator between lifetime abuse and CVD as well as between lifetime
      abuse and CVD risk behaviors. CONCLUSIONS AND CLINICAL IMPLICATIONS: To better
      promote cardiovascular health among women and direct appropriate interventions,
      nurses need to understand the complex web by which abuse may increase the risk
      for CVD. In addition, nurses need to not only pay attention to an abuse history
      and symptoms of depression for women presenting with CVD symptoms but also
      address CVD risk among women with abusive histories.

PMID- 24108228
TI  - Increased risk of atrial fibrillation and stroke during active stages of
      inflammatory bowel disease: a nationwide study.
AB  - AIMS: Inflammation is considered to play a role in the development of atrial
      fibrillation (AF). Hence inflammatory bowel disease (IBD) may be associated with
      AF. We therefore examined the incidence of AF and stroke in patients with IBD.
      METHODS AND RESULTS: From Danish nationwide registries 1996-2011, we identified
      24 499 patients with new-onset IBD and 236 275 age- and sex-matched controls.
      Poisson regression analyses with continuously updated covariates were used to
      estimate incidence rate ratios (IRRs) of AF and stroke. Disease activity stages
      of flare (new disease activity), persistent activity, and remission were defined
      by corticosteroid prescriptions, IBD hospital admissions, and biological
      treatment. Inflammatory bowel disease patients had a mean age of 43.9 years,
      53.9% were women, and mean follow-up was 6.8 years. Among IBD patients, 685 had
      AF and 549 had a stroke, corresponding to incidence rates per 1000 person-years
      of 4.16 vs. 2.70 for AF and 3.33 vs. 2.44 for stroke, compared with matched
      controls. Overall IBD-associated risk of AF corresponded to IRR 1.26 (1.16-1.36),
      but was driven by increased AF incidence during IBD flares [IRR 2.63 (2.26-3.06)]
      and persistent activity [IRR 2.06 (1.67-2.55)], whereas no increased AF risk was
      observed in remission periods [IRR 0.97 (0.88-1.08)]. Likewise increased stroke
      risk was exclusively found during active IBD [IRRs: 1.57 (1.27-1.93), 1.71 (1.32
      2.21), and 1.04 (0.93-1.15) for flares, persistent activity, and remission,
      respectively]. CONCLUSION: Active IBD is associated with increased risk of AF and
      stroke. These findings may be relevant to clinical practice.

PMID- 24108229
TI  - Pulmonary vein isolation in patients with Brugada syndrome and atrial
      fibrillation: a 2-year follow-up.
AB  - AIMS: Pharmacological treatment of atrial fibrillation (AF) in the setting of
      Brugada syndrome (BS) might be challenging as many antiarrhythmic drugs (AADs)
      with sodium channel blocking properties might expose the patients to the
      development of ventricular arrhythmias. Moreover, patients with BS and
      implantable cardioverter-defibrillator (ICD) might experience inappropriate
      shocks because of AF with rapid ventricular response. The role of pulmonary vein
      isolation (PVI) in patients with BS and recurrent episodes of AF has not been
      established yet. In this study, we analysed the outcome of PVI using
      radiofrequency energy or cryoballoon (CB) ablation at 2 years follow-up. METHODS
      AND RESULTS: Consecutive patients with BS having undergone PVI for drug-resistant
      paroxysmal AF were eligible for this study. Nine patients (three males; mean age:
      52 +/- 26 years) were included. Six patients (67%) had an ICD implanted of whom
      three had inappropriate shocks because of rapid AF. At a mean 22.1 +/- 6.4 months
      follow-up, six patients (67%) were free of AF without AADs. None of the three
      patients who had experienced inappropriate ICD interventions for AF had further
      ICD shocks after ablation. CONCLUSION: In our study PVI can be an effective and
      safe procedure to treat patients with BS and recurrent episodes of paroxysmal AF.

PMID- 24108230
TI  - Pharmacological cardioversion of atrial fibrillation with vernakalant: evidence
      in support of the ESC Guidelines.
AB  - Pharmacological rhythm control (often including electrical or pharmacological
      cardioversion) is an integral part of therapy for atrial fibrillation (AF)
      worldwide. Antiarrhythmic drug strategies would be preferred in many patients
      provided effective and safe antiarrhythmic agents are available. Also,
      pharmacological cardioversion could be the preferred option if the limitations of
      currently available drugs, such as restriction to patients without structural
      heart disease (flecainide and propafenone), risk of torsade de pointes
      (ibutilide), and slow onset of action (amiodarone), were overcome. The
      intravenous formulation of vernakalant (Brinavess, Cardiome) has been approved
      for pharmacological cardioversion of recent-onset AF (<=7 days) and early (<=3
      days) post-operative AF in the European Union, Iceland, and Norway. Vernakalant
      has a high affinity to ion channels specifically involved in repolarization of
      atrial tissue and has minimal effects in the ventricles and thus, is thought to
      have a low proarrhythmic potential. Vernakalant is administered as a 10 min
      infusion of 3 mg/kg, and if AF persists after 15 min, an additional dose of 2
      mg/kg can be given. The efficacy and safety of the drug has been extensively
      investigated in randomized controlled trials against placebo and an active
      comparator (amiodarone). The placebo-extracted efficacy of vernakalant is ~47%. A
      significant advantage is a rapid effect, with the median to conversion ranging
      between 8 and 14 min, with the majority of patients (75-82%) converting after the
      first dose. Vernakalant retained its efficacy in subgroups of patients with
      associated cardiovascular disease such as hypertension and ischaemic heart
      disease, but its benefit may be lower and risk of adverse effects is higher in
      patients with heart failure. In the post-market reports, cardioversion rates with
      vernakalant are 65-70%. This review focuses on the role of vernakalant in
      pharmacological cardioversion for AF. 

PMID- 24108231
TI  - Safety and efficacy of strategic implantable cardioverter-defibrillator
      programming to reduce the shock delivery burden in a primary prevention patient
      population.
AB  - AIMS: Strategically chosen ventricular tachycardia (VT)/ventricular fibrillation
      (VF) detection and therapy parameters aimed at reducing shock deliveries were
      proven effective in studies that utilized single manufacturer devices with a
      follow-up of up to 1 year. Whether these beneficiary effects can be generalized
      to additional manufacturers and be maintained for longer periods is to be
      determined. Our aim was to evaluate the durability and applicability of the
      programming of strategic implantable cardioverter-defibrillators (ICDs) of
      various manufacturers, which is aimed at reducing the shock delivery burden in
      primary prevention ICD recipients. METHODS AND RESULTS: A retrospective analysis
      of prospectively collected data of 300 ICD recipients of various manufacturers
      was conducted; 160 devices were strategically programmed to reduce shocks and 140
      were not. The primary endpoint was the composite of death and appropriate shocks.
      Additional outcomes were inappropriate shocks, syncope events, and non-sustained
      VTs. At a median follow-up of 24 months, 19 patients died, 31 received
      appropriate shocks, and 41 received inappropriate shocks. Multivariate analysis
      showed that strategic programming dedicated to shock reduction was associated
      with a 64% risk reduction in the primary endpoint [hazard ratio (HR): 0.13-0.93;
      P = 0.03] and a 70% reduction in inappropriate shock deliveries (HR: 0.16-0.72; P
      = 0.01). Very few syncope events occurred (five patients, 1.6%), and there was no
      between-group difference in this outcome. CONCLUSION: Utilization of
      strategically chosen VT/VF detection and therapy parameters was found to be
      effective and safe in ICDs of various manufacturers at a median follow-up period
      of 2 years among primary prevention patients.

PMID- 24108232
TI  - Comparison of Medical Costs of Patients With Atrial Fibrillation Unsuitable for
      Warfarin Treatment With Apixaban or Aspirin Based on AVERROES Trial.
AB  - BACKGROUND: The AVERROES trial name is the following: The Apixaban Versus
      Acetylsalicylic Acid (ASA) to Prevent Stroke in Atrial Fibrillation Patients Who
      Have Failed or Are Unsuitable for Vitamin K Antagonist Treatment (AVERROES) trial
      demonstrated that apixaban reduced the risk of stroke relative to aspirin,
      without significantly increasing major bleeding risk in patients with atrial
      fibrillation (AF) considered unsuitable for warfarin therapy. Based on AVERROES
      trial results, this study compared the medical costs for clinical end points
      among patients with AF treated with either apixaban or aspirin. METHODS: Medical
      costs per patient-year for clinical events were determined. Based on clinical
      event rates for patients in the AVERROES trial, medical costs excluding drug
      costs were estimated for apixaban- and aspirin-treated patient groups. RESULTS
      AND CONCLUSIONS: Based on AVERROES trial results, among patients with AF
      unsuitable for warfarin therapy, apixaban use was estimated to be associated with
      a mean medical cost avoidance of US$735 in a patient-year relative to aspirin.
      The primary driver was the significant reduction in ischemic stroke rate. The
      medical cost reduction associated with apixaban use was consistent in sensitivity
      analyses.

PMID- 24108233
TI  - Micro magnetofluidics: droplet manipulation of double emulsions based on
      paramagnetic ionic liquids.
AB  - The ability to control and manipulate discrete fluid droplets by magnetic fields
      offers new opportunities in microfluidics. A surfactant-free and easy to realize
      technique for the continuous generation of double emulsion droplets, composed of
      an organic solvent and a paramagnetic ionic liquid, is applied. The inner phase
      of the emulsion droplet consists of imidazolium-based ionic liquids with either
      iron, manganese, nickel or dysprosium containing anions which provide
      paramagnetic behaviour. The double emulsion droplets are dispersed in a
      continuous phase of FC-40. All substances - the organic phase, the paramagnetic
      ionic liquid and the continuous phase -are immiscible. The magnetic properties of
      ionic liquids allow, through the influence of external magnetic fields, the
      manipulation of individual emulsion droplets such as capture and release,
      rotation and distortion. Arrays of magnets allow a coalescence of emulsion
      droplets and their subsequent mixing by flowing through an alternating permanent
      magnetic field. In addition, the double emulsion droplets can be split and
      reunified, or continuously separated into their original phases. 

PMID- 24108234
TI  - Missed opportunities for HIV testing in pregnant women and children living in
      France.
AB  - We describe 48 cases of HIV-1-infected children newly diagnosed in 2006 to 2012
      in France. Native French children were born to women whose HIV testing were
      mostly missed (13.6%), offered late (9.1%) or negative at start of pregnancy and
      not subsequently reoffered (54.5%). HIV testing of immigrant children were
      performed late after arrival, despite prompt access to healthcare structures. HIV
      testing strategies need to be improved. 

PMID- 24108235
TI  - Chronic hyperaldosteronism in cryptochrome-null mice induces high-salt- and blood
      pressure-independent kidney damage in mice.
AB  - Although aldosterone has an essential role in controlling electrolyte and body
      fluid homeostasis, aldosterone also exerts certain pathological effects on the
      kidney. Several previous studies have attempted to examine these deleterious
      effects. However, the majority of these studies were performed using various
      injury models, including high-salt treatment and/or mineralocorticoid
      administration, by which the kidney changes observed were not only due to
      aldosterone but also due to prior injury caused by salt and hypertension. In the
      present study, we investigated aldosterone's pathological effect on the kidney
      using a mouse model with a high level of endogenous aldosterone. We used
      cryptochrome-null (Cry 1, 2 DKO) mice characterized by high aldosterone levels
      and low plasma renin activity and observed that even under normal salt exposure
      conditions, these mice showed increased albumin excretion and kidney tubular
      injury, decreased nephrin expression and increased reactive oxygen species
      production in the absence of hypertension. Exposure to high salt levels
      exacerbated the kidney damage observed in these mice. Moreover, we noted that
      decreasing blood pressure without blocking aldosterone action did not provide
      beneficial effects to the kidney in high-salt-treated Cry 1, 2 DKO mice. Thus,
      our findings support the hypothesis that aldosterone has deleterious effects on
      the kidney independent of high-salt exposure and high blood pressure. 

PMID- 24108236
TI  - Postprandial hypotension detected through home blood pressure monitoring: a
      frequent phenomenon in elderly hypertensive patients.
AB  - Postprandial hypotension (PPH) is a frequently under-recognized entity associated
      with increased morbidity and mortality. The prevalence of PPH detected through
      home blood pressure monitoring (HBPM) is unknown. To determine the prevalence and
      clinical predictors of PPH in hypertensive patients assessed through HBPM.
      Hypertensive patients of 18 years or older underwent home blood pressure (BP)
      measurements (duplicate measurements for 4 days: in the morning, 1 h before and 1
      h after their usual lunch, and in the evening; OMRON 705 CP). PPH was defined as
      a meal-induced systolic BP decrease of >=20 mm Hg. Variables identified as
      relevant predictors of PPH were entered into a multivariate logistic regression
      analysis. In total, 230 patients were included in the analysis, with a median age
      of 73.6 (interquartile range 16.9) years, and 65.2% were female. The prevalence
      of PPH (at least one episode) was 27.4%. Four variables were independently
      associated with PPH: age of 80 years or older (odds ratio (OR) 3.45, 95%
      confidence interval (CI) 1.35-8.82), body mass index (BMI) (OR 0.88, 95%CI 0.81
      0.96), office systolic BP (OR 1.03, 95%CI 1.01-1.05) and a history of
      cerebrovascular disease (OR 3.29, 95%CI 1.03-10.53). PPH after a typical meal is
      a frequent phenomenon that can be detected through HBPM. Easily measurable
      parameters in the office such as older age, higher systolic BP, lower BMI and a
      history of cerebrovascular disease may help to detect patients at risk of PPH who
      would benefit from HBPM.

PMID- 24108238
TI  - A meta-analysis of randomized controlled trials of azilsartan therapy for blood
      pressure reduction.
AB  - Although there have been a number of azilsartan trials, no meta-analysis of the
      findings has been conducted to date. We performed the first meta-analysis of
      randomized controlled trials of azilsartan therapy for the reduction of blood
      pressure (BP) in patients with hypertension. MEDLINE, EMBASE and the Cochrane
      Central Register of Controlled Trials were searched from the beginning of the
      records through March 2013 using web-based search engines (PubMed and OVID).
      Eligible studies were prospective randomized controlled trials of azilsartan
      (including azilsartan medoxomil) vs. any control therapy that reported clinic or
      24-h mean BP as an outcome. For each study, data for the changes from baseline to
      final clinic systolic BP (SBP) and diastolic BP (DBP) in both the azilsartan
      group and the control group were used to generate mean differences and 95%
      confidence intervals (CIs). Of 27 potentially relevant articles screened
      initially, 7 reports of randomized trials of azilsartan or azilsartan medoxomil
      therapy enrolling a total of 6152 patients with hypertension were identified and
      included. Pooled analysis suggested a significant reduction in BP changes among
      patients randomized to 40 mg of azilsartan vs. control therapy (clinic SBP: -4.20
      mm Hg; 95% CI: -6.05 to -2.35 mm Hg; P<0.00001; clinic DBP: -2.58 mm Hg; 95% CI: 
      3.69 to -1.48 mm Hg; P<0.00001; 24-h mean SBP: -3.33 mm Hg; 95% CI: -4.74 to 
      1.93 mm Hg; P<0.00001; 24-h mean DBP: -2.12 mm Hg; 95% CI: -2.74 to -1.49 mm Hg;
      P<0.00001). In conclusion, azilsartan therapy appears to provide a greater
      reduction in BP than control therapy in patients with hypertension.

PMID- 24108239
TI  - Lower Framingham risk score and the absence of hypertension are associated with
      the morning peak in the circadian variation of ST-elevation myocardial infarction
      onset.
AB  - There are few studies analyzing the influences of coronary risk factors on the
      circadian variation of ST-elevation myocardial infarction (STEMI). Between 2008
      and 2011, 293 patients were admitted to Miyazaki Prefectural Nobeoka Hospital
      with STEMI. The onset time of STEMI was identified in 280 patients (age, 70.5+/
      11.7 years; male subjects, 68%; hypertension (HT), 80%; diabetes mellitus, 28%;
      current smoking (cSM), 33%; Framingham risk score (FRS), 8.77+/-3.28). The day
      was divided into six 4-h periods, with the morning peak between 0800 and 1200
      hours. The frequency of HT was significantly lower in the morning incidence group
      than in the nighttime incidence group. Multivariate logistic regression analysis
      revealed that the prevalence of HT was the only independent variable associated
      with the morning peak of STEMI (odds ratio (OR), 0.43; 95% confidence interval
      (95% CI), 0.23-0.83; P=0.01) and that cSM was significantly associated with the
      nighttime peak of STEMI (OR, 1.96; 95% CI, 1.01-3.80; P=0.04). A comprehensive
      evaluation using the FRS showed that the FRS was significantly lower in the
      morning incidence group than in the nighttime incidence group and the other time
      incidence group (7.95+/-3.47 vs. 9.14+/-2.89 vs. 9.06+/-3.25, P<0.01), and that
      having a lower FRS was associated with the morning peak of STEMI (OR, 1.12; 95%
      CI, 1.02-1.21; P=0.01). A lower FRS and non-HT status are associated with the
      morning peak in the circadian variation of STEMI onset. The morning incidence of
      STEMI might be affected by pathogenic factors other than the classic coronary
      risk factors. 

PMID- 24108237
TI  - Comparative effects of telmisartan and valsartan as add-on agents for
      hypertensive patients with morning blood pressure insufficiently controlled by
      amlodipine monotherapy.
AB  - The aim of this study was to determine the efficacies of valsartan and
      telmisartan as add-on agents for the control of morning blood pressure (BP) in
      patients already on amlodipine monotherapy. A total of 414 hypertensive patients
      were prospectively enrolled in a 4-week run-in period when they were treated with
      amlodipine (5 mg/day), and home BP was measured in the morning and evening.
      Patients with home systolic BP (SBP) being 135-159 mm Hg in the morning at the
      end of the run-in period were randomized to additional treatment with valsartan
      (80 mg/day) or with telmisartan (40 mg/day) for 8 weeks. The primary endpoint was
      the change in morning home BP, and secondary endpoints included variability of
      morning home BP. Of the 282 patients randomized, 262 patients (n=131, in each
      treatment) completed the protocols. Demographic parameters and baseline morning
      SBP/diastolic BP (DBP) (146.3+/-7.1/84.8+/-9.3 vs. 146.0+/-7.1/84.2+/-9.1 mm Hg)
      were comparable in the valsartan group and telmisartan group, and changes in
      SBP/DBP after 8-week treatment were not significantly different between the two
      groups (-7.4+/-10.6/-3.9+/-6.1 vs. -8.3+/-9.9/-5.0+/-5.9 mm Hg). Valsartan
      significantly increased individual standard deviation and variation coefficient
      of morning SBP, but telmisartan did not change either of these indices of SBP
      variation. In subgroups with baseline SBP being above the median (145.2 mm Hg),
      change in DBP was significantly larger by telmisartan than by valsartan (-6.3+/
      5.6 vs. -3.9+/-6.7 mm Hg, P<0.05). These results suggest that telmisartan is more
      useful than valsartan as an add-on agent for reducing the level and variability
      of morning BP in patients on amlodipine monotherapy. 

PMID- 24108240
TI  - A 3D mesoporous polysulfone-carbon nanotube anode for enhanced bioelectricity
      output in microbial fuel cells.
AB  - A facile fabrication method was developed to construct a three-dimensional (3D)
      mesoporous anode by coating single-walled carbon nanotubes (SWCNTs) on a
      mesoporous polysulfone matrix (MPPS) for microbial fuel cells (MFCs). Owing to
      highly active surface areas and efficient extracellular electron transfer between
      Shewanella cells and the anode, the MFC achieved an electricity output of 1410 mW
      m(-2), being one of the highest among the reported Shewanella-based MFCs. 

PMID- 24108242
TI  - Accuracy of frame-based stereotactic depth electrode implantation during
      craniotomy for subdural grid placement.
AB  - BACKGROUND: Frame-based stereotaxy and open craniotomy may seem mutually
      exclusive, but invasive electrophysiological monitoring can require broad
      sampling of the cortex and precise targeting of deeper structures. OBJECTIVES:
      The purpose of this study is to describe simultaneous frame-based insertion of
      depth electrodes and craniotomy for placement of subdural grids through a single
      surgical field and to determine the accuracy of depth electrodes placed using
      this technique. METHODS: A total of 6 patients with intractable epilepsy
      underwent placement of a stereotactic frame with the center of the planned
      cranial flap equidistant from the fixation posts. After volumetric imaging,
      craniotomy for placement of subdural grids was performed. Depth electrodes were
      placed using frame-based stereotaxy. Postoperative CT determined the accuracy of
      electrode placement. RESULTS: A total of 31 depth electrodes were placed. Mean
      distance of distal electrode contact from the target was 1.0 +/- 0.15 mm. Error
      was correlated to distance to target, with an additional 0.35 mm error for each
      centimeter (r = 0.635, p < 0.001); when corrected, there was no difference in
      accuracy based on target structure or method of placement (prior to craniotomy
      vs. through grid, p = 0.23). CONCLUSION: The described technique for craniotomy
      through a stereotactic frame allows placement of subdural grids and depth
      electrodes without sacrificing the accuracy of a frame or requiring staged
      procedures.

PMID- 24108243
TI  - European health systems must adapt to austerity, conference hears.

PMID- 24108244
TI  - Candidate malaria vaccine becomes less effective over time, study shows.

PMID- 24108241
TI  - Apical membrane antigen 1 mediates apicomplexan parasite attachment but is
      dispensable for host cell invasion.
AB  - Apicomplexan parasites invade host cells by forming a ring-like junction with the
      cell surface and actively sliding through the junction inside an intracellular
      vacuole. Apical membrane antigen 1 is conserved in apicomplexans and a long
      standing malaria vaccine candidate. It is considered to have multiple important
      roles during host cell penetration, primarily in structuring the junction by
      interacting with the rhoptry neck 2 protein and transducing the force generated
      by the parasite motor during internalization. Here, we generate Plasmodium
      sporozoites and merozoites and Toxoplasma tachyzoites lacking apical membrane
      antigen 1, and find that the latter two are impaired in host cell attachment but
      the three display normal host cell penetration through the junction. Therefore,
      apical membrane antigen 1, rather than an essential invasin, is a dispensable
      adhesin of apicomplexan zoites. These genetic data have implications on the use
      of apical membrane antigen 1 or the apical membrane antigen 1-rhoptry neck 2
      interaction as targets of intervention strategies against malaria or other
      diseases caused by apicomplexans. 

PMID- 24108245
TI  - European parliament refuses to classify e-cigarettes as medicines.

PMID- 24108246
TI  - Mechanistic aspects of dinitrogen cleavage and hydrogenation to produce ammonia
      in catalysis and organometallic chemistry: relevance of metal hydride bonds and
      dihydrogen.
AB  - Dinitrogen cleavage and hydrogenation by transition-metal centers to produce
      ammonia is central in industry and in Nature. After an introductory section on
      the thermodynamic and kinetic challenges linked to N2 splitting, this tutorial
      review discusses three major classes of transition-metal systems (homogeneous,
      heterogeneous and biological) capable of achieving dissociation and hydrogenation
      of dinitrogen. Molecular complexes, solid-state Haber-Bosch catalytic systems,
      silica-supported tantalum hydrides and nitrogenase will be discussed. Emphasis is
      focused on the reaction mechanisms operating in the process of dissociation and
      hydrogenation of dinitrogen, and in particular on the key role played by metal
      hydride bonds and by dihydrogen in such reactions. 

PMID- 24108247
TI  - Serum multivalent cationic pattern: speculation on the efficient approach for
      detection of Alzheimer's disease.
AB  - Alzheimer's disease (AD) is increasingly becoming one of the greatest medical
      challenges. Due to the social and financial burden of AD, detection of AD in its
      early stages is a topic of major research interest. Thus, emergence of well
      validated screening methods for fast detection of AD in the early stages would be
      of great importance. It is now recognized that the homeostasis and serum
      bioavailability of multivalent cations (e.g. zinc, copper, and iron) are
      disturbed in AD. Using a standard chemometric approach (hierarchical clustering
      analysis), we find that the serum concentrations of an array of such multivalent
      cations can be a fingerprint for identification of AD patients. This may pave the
      way for a reliable, efficient, and inexpensive method for early detection and
      treatment of AD. 

PMID- 24108248
TI  - A dose-ranging study of 0.5% bupivacaine or ropivacaine on the success and
      duration of the ultrasound-guided, nerve-stimulator-assisted sciatic nerve block:
      a double-blind, randomized clinical trial.
AB  - BACKGROUND AND OBJECTIVES: Before bifurcation, the sciatic nerve is composed of 2
      component nerves encased in a common investing extraneural layer (CIEL). We
      examined the effect of various volumes injected beneath the CIEL on the success
      and duration of sciatic nerve block. METHODS: Ultrasound-guided nerve-stimulator
      assisted sciatic nerve blocks were performed on 142 subjects. Subjects were
      randomized into 14 groups (0.5% ropivacaine or bupivacaine) with epinephrine
      1:300,000 in volumes ranging from 2.5 to 30 mL. Successful block was defined as a
      complete sensory and motor block at 60 minutes. The minimum threshold current,
      time to complete block, duration of sensory and motor block, postoperative pain,
      and analgesic requirements were recorded. RESULTS: The mean threshold current
      external to the CIEL was 0.52 (0.15) mA compared to 0.19 (0.09) mA beneath the
      CIEL (P < 0.001). Successful block was achieved in 30 of 40 subjects that
      received 5 mL or less of ropivacaine or bupivacaine compared with 97 of 99 that
      received 10 mL or greater volume (P = 0.006). Injection volumes greater than or
      equal to 10 mL produced complete sensory and motor block within 30 minutes.
      Volumes greater than 10 mL did not extend the duration of the sensory or motor
      block. Injection volumes of 2.5 and 5 mL were associated with delayed onset and
      decreased block duration and a greater fraction of subjects experiencing pain
      behind the knee. CONCLUSIONS: Injecting 10 mL of 0.5% bupivacaine or ropivacaine
      below the CIEL produces comparable onset and duration of sensory and motor
      blockade as volumes as large as 30 mL.

PMID- 24108249
TI  - A scoping review of the evidence for teaching ultrasound-guided regional
      anesthesia.
AB  - A scoping review was performed to assess published evidence regarding how best to
      teach ultrasound-guided regional anesthesia (UGRA). The literature search yielded
      205 articles, of which 35 met the inclusion criteria. Current literature on the
      topic can be divided into 3 main themes: the development of motor skills,
      learning and teaching sonoanatomy, and understanding of the requirements for
      establishing a UGRA education program and evaluation. We discuss the current
      status and future direction of research on UGRA training. 

PMID- 24108250
TI  - Experience with the treatment of bisphosphonate-related osteonecrosis of the jaw.
AB  - AIM: This article covers the authors' experience with the treatment of
      bisphosphonate-related osteonecrosis of the jaw in 11 individuals. METHODS: A
      retrospective study of patients diagnosed and treated for bisphosphonate-related
      osteonecrosis of the jaw at the Department of Dentistry, University Hospital
      Hradec Kralove during the period January 2006 to October 2012. The treatment
      protocol consisted of antimicrobial mouth rinses and systemic antibiotic
      administration according to the stage of the disease. Additional surgical
      debridement and sequestrectomy in combination with antimicrobial therapy was
      performed in two cases. RESULTS: Complete healing was achieved in six patients.
      In two cases, satisfactory healing was noted. Stage of the disease was lowered
      and only a small area of asymptomatic necrotic bone of up to five mm in diameter
      persisted. Two patients developed a stable disease without progression. In one
      patient, the disease progressed to the third stage with osteonecrosis involving
      all quadrants of both jaws. CONCLUSION: From these data it was concluded that
      conservative approach in the treatment of bisphosphonate-related osteonecrosis of
      the jaw led to symptom regression but was not curative. Surgical intervention,
      however, bears the risk of further progression of the osteonecrosis and must be
      carefully planned with respect to the patient's general health status and life
      expectancy. The treatment of bisphosphonate-related osteonecrosis of the jaw is
      generally difficult. For this reason, prevention plays a predominant role in the
      management of the disease.

PMID- 24108251
TI  - Implementing emergency manuals: can cognitive aids help translate best practices
      for patient care during acute events?
AB  - In this article, we address whether emergency manuals are an effective means of
      helping anesthesiologists and perioperative teams apply known best practices for
      critical events. We review the relevant history of such cognitive aids in health
      care, as well as examples from other high stakes industries, and describe why
      emergency manuals have a role in improving patient care during certain events. We
      propose 4 vital elements: create, familiarize, use, and integrate, necessary for
      the widespread, successful development, and implementation of medical emergency
      manuals, using the specific example of the perioperative setting. The details of
      each element are presented, drawing from the medical literature as well as from
      our combined experience of more than 30 years of observing teams of
      anesthesiologists managing simulated and real critical events. We emphasize the
      importance of training clinicians in the use of emergency manuals for education
      on content, format, and location. Finally, we discuss cultural readiness for
      change, present a system example of successful integration, and highlight the
      importance of further research on the implementation of emergency manuals. 

PMID- 24108253
TI  - Automated, real-time fresh gas flow recommendations alter isoflurane consumption
      during the maintenance phase of anesthesia in a simulator-based study.
AB  - BACKGROUND: The Low Flow Wizard (LFW) provides real-time guidance for user
      optimization of fresh gas flow (FGF) settings during general inhaled anesthesia.
      The LFW can continuously inform users whether it determines their FGF to be too
      little, efficient, or too much, and its color-coded recommendations respond in
      real time to changes in FGF performed by users. Our study objective was to
      determine whether the LFW feature, as implemented in the Drager Apollo
      workstation, alters FGF selection and thereby volatile anesthetic consumption
      without affecting patient care. METHODS: To reduce potentially confounding
      variables, we used a human patient simulator that consumes and exhales volatile
      anesthetics. Standard monitoring was provided for the patient initially with
      invasive arterial blood pressure added after anesthetic induction. In this within
      group study, each of 17 participants acted as his or her own control. Each
      participant was asked to anesthetize an identical simulated patient twice using a
      Drager Apollo workstation, first with the LFW feature disabled and subsequently
      enabled. The volatile anesthetic was isoflurane. Both simulation runs were set up
      to have similar time durations for the different phases of anesthesia: induction,
      incision, and maintenance. Emergence was not simulated. The isoflurane vaporizer
      was weighed before and after each simulation run on a digital scale to verify
      total computed volatile liquid anesthetic consumption. In addition, the product
      of FGF (reported by the Apollo) times the isoflurane volumetric concentration
      (sampled by a multigas analyzer at the equivalent of the FGF hose for the Apollo)
      was integrated over time to obtain isoflurane consumption rate (on-the-fly
      anesthetic consumption rate measurement). RESULTS: The maintenance isoflurane
      consumption rate and FGF were significantly lower with the LFW display enabled
      than without (P = 0.005). The mean reduction in FGF was 53.6% (95% confidence
      interval, 39.2%-67.9%). There was no significant difference in alveolar
      isoflurane concentration (P = 0.13 for differences <0.1%). The isoflurane
      consumption measurement closely matched the consumption measured via the digital
      scale. CONCLUSIONS: Our data in a simulated anesthetic suggest that enabling the
      display of FGF efficiency data by the LFW results in a median percent reduction
      in volatile liquid anesthetic consumption rate of 53.2%. Since the lower limit of
      the 95% confidence interval for the median is 39.4%, this finding is likely to
      translate into cost savings and less waste anesthetic gas generated in the
      clinical setting and released into the atmosphere.

PMID- 24108252
TI  - Liposomal bupivacaine as a single-injection peripheral nerve block: a dose
      response study.
AB  - BACKGROUND: Currently available local anesthetics approved for single-injection
      peripheral nerve blocks have a maximum duration of <24 hours. A liposomal
      bupivacaine formulation (EXPAREL, Pacira Pharmaceuticals, Inc., San Diego, CA),
      releasing bupivacaine over 96 hours, recently gained Food and Drug Administration
      approval exclusively for wound infiltration but not peripheral nerve blocks.
      METHODS: Bilateral single-injection femoral nerve blocks were administered in
      healthy volunteers (n = 14). For each block, liposomal bupivacaine (0-80 mg) was
      mixed with normal saline to produce 30 mL of study fluid. Each subject received 2
      different doses, 1 on each side, applied randomly in a double-masked fashion. The
      end points included the maximum voluntary isometric contraction (MVIC) of the
      quadriceps femoris muscle and tolerance to cutaneous electrical current in the
      femoral nerve distribution. Measurements were performed from baseline until
      quadriceps MVIC returned to 80% of baseline bilaterally. RESULTS: There were
      statistically significant dose responses in MVIC (0.09%/mg, SE = 0.03, 95%
      confidence interval [CI], 0.04-0.14, P = 0.002) and tolerance to cutaneous
      current (-0.03 mA/mg, SE = 0.01, 95% CI, -0.04 to -0.02, P < 0.001), however, in
      the opposite direction than expected (the higher the dose, the lower the observed
      effect). This inverse relationship is biologically implausible and most likely
      due to the limited sample size and the subjective nature of the measurement
      instruments. While peak effects occurred within 24 hours after block
      administration in 75% of cases (95% CI, 43%-93%), block duration usually lasted
      much longer: for bupivacaine doses >40 mg, tolerance to cutaneous current did not
      return to within 20% above baseline until after 24 hours in 100% of subjects (95%
      CI, 56%-100%). MVIC did not consistently return to within 20% of baseline until
      after 24 hours in 90% of subjects (95% CI, 54%-100%). Motor block duration was
      not correlated with bupivacaine dose (0.06 hour/mg, SE = 0.14, 95% CI, -0.27 to
      0.39, P = 0.707). CONCLUSIONS: The results of this investigation suggest that
      deposition of a liposomal bupivacaine formulation adjacent to the femoral nerve
      results in a partial sensory and motor block of >24 hours for the highest doses
      examined. However, the high variability of block magnitude among subjects and
      inverse relationship of dose and response magnitude attests to the need for a
      phase 3 study with a far larger sample size, and that these results should be
      viewed as suggestive, requiring confirmation in a future trial.

PMID- 24108254
TI  - Review of experimental studies in social psychology of small groups when an
      optimal choice exists and application to operating room management decision
      making.
AB  - Because operating room (OR) management decisions with optimal choices are made
      with ubiquitous biases, decisions are improved with decision-support systems. We
      reviewed experimental social-psychology studies to explore what an OR leader can
      do when working with stakeholders lacking interest in learning the OR management
      science but expressing opinions about decisions, nonetheless. We considered
      shared information to include the rules-of-thumb (heuristics) that make intuitive
      sense and often seem "close enough" (e.g., staffing is planned based on the
      average workload). We considered unshared information to include the relevant
      mathematics (e.g., staffing calculations). Multiple studies have shown that group
      discussions focus more on shared than unshared information. Quality decisions are
      more likely when all group participants share knowledge (e.g., have taken a
      course in OR management science). Several biases in OR management are caused by
      humans' limited abilities to estimate tails of probability distributions in their
      heads. Groups are more susceptible to analogous biases than are educated
      individuals. Since optimal solutions are not demonstrable without groups sharing
      common language, only with education of most group members can a knowledgeable
      individual influence the group. The appropriate model of decision-making is
      autocratic, with information obtained from stakeholders. Although such decisions
      are good quality, the leaders often are disliked and the decisions considered
      unjust. In conclusion, leaders will find the most success if they do not bring OR
      management operational decisions to groups, but instead act autocratically while
      obtaining necessary information in 1:1 conversations. The only known route for
      the leader making such decisions to be considered likable and for the decisions
      to be considered fair is through colleagues and subordinates learning the
      management science. 

PMID- 24108255
TI  - FIBTEM PLUS provides an improved thromboelastometry test for measurement of
      fibrin-based clot quality in cardiac surgery patients.
AB  - BACKGROUND: The viscoelastic functional fibrinogen (FF) and FIBTEM assays measure
      the contribution of fibrin to clot strength. Inhibition of platelet function is a
      necessary precondition for these tests to work. We investigated a novel test for
      measuring fibrin-based clotting, FIBTEM PLUS, in cardiac surgery and compared it
      with FF and FIBTEM. METHODS: A prospective, observational study was performed
      which included 30 patients undergoing cardiac surgery with cardiopulmonary bypass
      (CPB). Blood samples were drawn at the beginning of surgery (pre-CPB),
      approximately 20 minutes before weaning from CPB and 5 minutes after heparin
      neutralization. FF, FIBTEM, and FIBTEM PLUS tests were performed in duplicate for
      all blood samples. Additional coagulation parameters, including platelet count,
      plasma fibrinogen levels, factor XIII activity, and heparin concentration, were
      also recorded for each sample. RESULTS: At all time points, the lowest mean
      maximum clot firmness (MCF) was observed with FIBTEM PLUS, although a
      statistically significant difference between FIBTEM and FIBTEM PLUS was observed
      only at baseline (mean values 22 vs 19 mm, P = 0.01; FF value for comparison:
      27.7 mm). FF maximum amplitude (MA) values were significantly higher than FIBTEM
      MCF and FIBTEM PLUS MCF pre-CPB, during CPB and after heparin neutralization (P
      <= 0.001 for FF MA versus FIBTEM MCF and for FF MA versus FIBTEM PLUS MCF at all
      time points). The difference between FIBTEM MCF and FIBTEM PLUS MCF correlated
      with platelet count (r = 0.46;P < 0.001), whereas differences between FF MA and
      FIBTEM MCF, or FF MA and FIBTEM PLUS MCF did not (r = -0.07, P = 0.51; r = 0.16,
      P = 0.12, respectively). Differences between the assays were unrelated to heparin
      levels, which decreased considerably after protamine administration compared with
      heparin levels recorded before weaning from CPB (decrease from 2.1 to 0.1 U/mL
      and from 2.8 to 0.2 U/mL for anti-factor IIa and anti-factor Xa, respectively).
      Agreement between duplicate measurements was similar with FIBTEM and FIBTEM PLUS
      assays and lower with FF. Significant positive correlations were found between
      MCF or MA and fibrinogen concentration (all P < 0.001); the highest correlation
      was with FIBTEM PLUS MCF (r = 0.70). CONCLUSION: The FIBTEM PLUS assay produces
      precise results. At baseline, it provides greater inhibition of platelets than
      FIBTEM, but there is no meaningful difference between FIBTEM PLUS and FIBTEM in
      patients with low platelet counts.

PMID- 24108256
TI  - A checklist for trauma and emergency anesthesia.

PMID- 24108257
TI  - The cost of resident scholarly activity and its effect on resident clinical
      experience.
AB  - BACKGROUND: Scholarly activity is an important aspect of the academic training of
      future anesthesiologists. However, residents' scholarly activity may reduce
      training caseloads and increase departmental costs. METHODS: We conducted this
      study within a large academic anesthesiology residency program with data from the
      4 graduating classes of 2009 through 2012. Scholarly activity included peer
      reviewed manuscripts, case reports, poster presentations at conferences, book
      chapters, or any other publications. It was not distinguished whether a resident
      was the principal investigator or a coinvestigator on a project. The following
      data were collected on each resident: months spent on a resident research
      rotation, number of scholarly projects completed, number of research conferences
      attended, and Accreditation Council for Graduate Medical Education case entries.
      Comparison was made between residents electing a resident research rotation with
      those who did not for (1) scholarly projects, (2) research conference attendance,
      and (3) Accreditation Council for Graduate Medical Education case numbers. Cost
      to the department for extra clinical coverage during residents' time spent on
      research activities was calculated using an estimated average cost of $675 +/-
      $176 (mean +/- SD) per day with local certified registered nurse anesthetist pay
      scales. RESULTS: Sixty-eight residents were included in the analyses. Twenty-four
      residents (35.3%) completed resident research rotations with an average duration
      of 3.7 months. Residents who elected resident research rotations completed more
      scholarly projects (5 projects [4-6]: median [25%-75% interquartile range] vs 2
      [0-3]; P < 0.0001), attended more research conferences (2 conferences [2-4] vs 1
      [0-2]; P < 0.0001), but experienced fewer cases (980 cases [886-1333] vs 1182
      [930-1420]; P <= 0.002) compared with those who did not elect resident research
      rotations. The estimated average cost to the department per resident who elected
      a resident research rotation was $13,500 +/- $9724 per month. The average
      resident time length away from duty for conference attendance was 3.2 +/- 0.2
      days, with an average cost to the department of $2160 +/- $565. The average
      annual departmental expense for resident conference travel was an additional
      $1424 +/- $133 per resident, as calculated from reimbursement data. Together, the
      estimated departmental cost for resident scholarly activity during the residency
      training period was $27,467 +/- $20,153 per resident. CONCLUSIONS: Residents'
      scholarly activities require significant departmental financial support.
      Residents who elected to spend months conducting research completed significantly
      more scholarly projects but experienced fewer clinical cases.

PMID- 24108258
TI  - Surgical procedures and outcomes among children with sickle cell disease.
AB  - BACKGROUND: Although children with sickle cell disease often undergo surgery,
      there are limited current epidemiological data for this pediatric population. We
      performed a database analysis to estimate population characteristics, surgical
      procedures, and perioperative outcomes in this population. METHODS: We queried
      the Nationwide Inpatient Sample Database from 2000 to 2010 for discharges
      pertaining to patients <18 years of age having a diagnosis of sickle cell disease
      who underwent 1 or more surgical procedures during that admission. We abstracted
      surgical procedures using the Clinical Classifications Software procedure codes
      and the ICD-9-CM procedure codes. We described characteristics of patients
      undergoing the 6 most common procedures. RESULTS: During 2000 to 2010, 3.6 % (SE
      0.12) of individual hospital discharges were of children with sickle cell disease
      who had undergone surgical procedures. The most frequent surgical procedures were
      cholecystectomy (1.47% [0.08]), tonsillectomy/adenoidectomy (0.81% [0.06]),
      splenectomy (0.62% [0.06]), repair of umbilical hernia (0.19% [0.02]), and
      appendectomy (0.17% [0.02]). Acute chest syndrome was recorded among 3.08% (0.60)
      of patients undergoing elective surgery. The incidence of stroke was 0.20%
      (0.11); death was reported in <11 patients (<0.20%). CONCLUSION: Surgical
      procedures such as cholecystectomy, tonsillectomy, splenectomy, hernia repair,
      and appendectomy account for a small but significant proportion of hospital
      admissions in children with sickle cell disease. Acute chest syndrome is among
      the most common complications of elective surgery, while stroke and death are
      rare.

PMID- 24108259
TI  - Remifentanil has a minimal direct effect on sinoatrial node pacemaker activity in
      the Guinea pig heart.
AB  - BACKGROUND: Whereas remifentanil administration is associated with severe
      bradycardia, it has yet to be fully investigated whether the negative
      chronotropic action of remifentanil is mediated by its direct action on
      sinoatrial (SA) node pacemaker activity in the heart versus indirect results of
      enhanced vagal activity. METHODS: We examined the effects of remifentanil and
      fentanyl on the spontaneous action potentials of guinea pig SA node cells at
      concentrations of 5, 10, 100, and 1000 nM using the amphotericin B-perforated
      whole-cell patch-clamp technique. Isolated guinea pig hearts were perfused in a
      Langendorff mode with 5, 10, 100, and 1000 nM remifentanil. RESULTS: The
      spontaneous firing rate and diastolic depolarization rate (DDR) of the SA node
      action potentials were 189.1 +/- 14.8 /min and 74.1 +/- 2.9 mV/s (n = 8),
      respectively, under control conditions, and were not significantly affected by
      exposure to 5 nM (P = 1.0 for both spontaneous firing rate and DDR; n = 6), 10 nM
      (P = 0.62 for spontaneous firing rate, P = 0.99 for DDR; n = 6), or 100 nM (P =
      0.23 for spontaneous firing rate, P = 0.38 for DDR; n = 6) remifentanil. However,
      1000 nM remifentanil modestly but significantly decreased the spontaneous firing
      rate (P = 0.0087) and DDR (P = 0.0072, n = 6). Remifentanil did not affect the
      heart rate of isolated Langendorff-perfused guinea pig hearts at concentrations
      of 5 nM (P = 0.98), 10 nM (P = 0.35), or 100 nM (P = 0.24) but significantly
      reduced the heart rate at 1000 nM (P < 0.0001). Fentanyl did not affect the
      spontaneous firing rate and DDR at concentrations of 5 nM (P = 1.0 for both
      spontaneous firing rate and DDR) and 10 nM (P = 0.62 for spontaneous firing rate,
      P = 0.79 for DDR), but it significantly reduced both at 100 nM (P = 0.00038 for
      spontaneous firing rate, P = 0.0080 for DDR) and 1000 nM (P < 0.0001 for both
      spontaneous firing rate and DDR). CONCLUSIONS: Clinically relevant concentrations
      (nanomolar order concentrations) of remifentanil do not produce significant
      direct effects on intrinsic cardiac automaticity; thus, suggesting that
      remifentanil-induced bradycardia in the clinical setting is independent of its
      direct cardiac effects.

PMID- 24108260
TI  - Adenosine-induced flow arrest to facilitate intracranial aneurysm clip ligation
      does not worsen neurologic outcome.
AB  - BACKGROUND: When temporary arterial occlusion of the parent artery is difficult
      for anatomical reasons, or when inadvertent aneurysmal rupture occurs during
      surgical dissection, adenosine administration can be used to produce flow arrest
      and brief, profound systemic hypotension that can facilitate intracranial
      aneurysm clip ligation. There is a concern, however, that the flow arrest and
      profound hypotension produced by adenosine, although brief, may cause cerebral
      ischemia and therefore worsen neurologic outcome compared with other techniques
      to facilitate aneurysm clip ligation. Therefore, we performed a retrospective,
      case-control study to determine whether adenosine-induced flow arrest had
      negative effects on the neurologic outcome of our patients. METHODS: We reviewed
      the perioperative records of all patients in our intracranial aneurysm surgery
      outcomes database between August 1, 2006, and June 15, 2012. The primary outcome
      was the presence or absence of a poor neurologic outcome 48 hours after surgery,
      with a modified Rankin scale score >2 being defined as a poor neurologic outcome.
      The neurologic outcome at the time of hospital discharge was a secondary outcome.
      Secondary outcomes related to cardiac morbidity included atrial or ventricular
      arrhythmia requiring treatment and elevated cardiac biomarkers consistent with
      ischemia (i.e., Troponin-I). RESULTS: During the study period, adenosine-induced
      flow arrest was used in 72 of the 413 patients (17.4%) who underwent intracranial
      aneurysm clip ligation. The difference in the incidence of poor neurological
      outcome, with or without the use of adenosine, was no larger than 15.7% at 48
      hours after surgery (P =0.524) or -12.7% at discharge (P = 0.741). In addition,
      the difference in the incidence of cardiac morbidity was no larger than -16.0%
      for persistent arrhythmia (P = 0.155) or -9.4% for biomarkers of myocardial
      ischemia (P = 0.898) in the initial 48 hours after surgery. CONCLUSION: When used
      to facilitate intracranial aneurysm clip ligation, adenosine-induced flow arrest
      was associated with no more than a 15.7% increase or a 12.7% decrease in the
      incidence of a poor neurologic outcome at either 48 hours or at the time of
      hospital discharge. In addition, adenosine use was not associated with cardiac
      morbidity in the perioperative period (i.e., persistent arrhythmia or biomarkers
      of cardiac ischemia).

PMID- 24108261
TI  - A phase Ib, dose-finding study of multiple doses of remimazolam (CNS 7056) in
      volunteers undergoing colonoscopy.
AB  - BACKGROUND: We performed the first multiple dose study of remimazolam designed to
      assess both the feasibility of maintaining suitable sedation during colonoscopy
      and reversing the sedative effects of remimazolam with flumazenil. METHODS:
      Healthy volunteers received fentanyl followed by remimazolam for sedation during
      colonoscopy. Three dose groups of 15 volunteers each received remimazolam in
      increasing initial doses, plus top-up doses to maintain sedation for a 30-minute
      period. In a separate double-blind crossover part of the trial, 6 volunteers were
      sedated with a single high dose of remimazolam, followed by flumazenil or placebo
      to reverse the sedation. RESULTS: Successful sedation that was adequate for
      colonoscopy was achieved in >70% of subjects. After the procedure, subjects
      rapidly recovered to fully alert, with a median of <10 minutes overall. Failures
      were due to the inability to sedate or adverse events, with 1 subject failing due
      to hypotension (arterial blood pressure 80/40) and low SpO2 (<90%). There were no
      serious adverse events reported, and no events that were unexpected with the
      combination of a benzodiazepine and fentanyl. The study also showed that sedation
      was rapidly reversible (1.0 minutes flumazenil vs 10.5 minutes placebo) without
      resedation. CONCLUSIONS: Remimazolam has the attributes of a sedative drug, with
      success rates comparable with recent studies of other drugs. Remimazolam provided
      adequate sedation in 33 of 44 subjects undergoing colonoscopy, and its sedative
      effects were easily reversed with flumazenil.

PMID- 24108262
TI  - The effect of endoplasmic reticulum stress on neurotoxicity caused by inhaled
      anesthetics.
AB  - BACKGROUND: The mechanisms by which inhaled anesthetics cause neurotoxicity are
      not well clarified. Exposure to inhaled anesthetics induces a release of Ca from
      the endoplasmic reticulum (ER) into the cytosol. Aberrant Ca mobilization may
      alter the protein-folding environment in the ER, causing ER stress. Binding
      immunoglobulin protein (BiP) is an ER chaperone that is critical to ER functions.
      Because ER stress leads to cellular dysfunction and apoptotic cell death, leading
      to diverse human disorders such as neurodegenerative diseases, we hypothesized ER
      stress may play a role in neurotoxicity caused by inhaled anesthetics. METHODS:
      We investigated the relationship between ER stress and neurodegeneration caused
      by inhaled anesthetics by using knock-in mice expressing a mutant BiP and
      neuronal culture cells. Neuronal culture cells and mutant BiP pregnant mice were
      exposed to 3% sevoflurane. The levels of BiP and C/EBP homologous protein (CHOP),
      a transcription factor related to cell death during ER stress, were evaluated by
      Western blot in neuronal cells and fetal brains delivered by cesarean delivery.
      Cell death in the fetal brains was evaluated with TUNEL staining. Statistical
      significance was assessed using unpaired t test and analysis of variance followed
      by multiple comparison tests. RESULTS: Sevoflurane exposure enhanced the
      expression of BiP and CHOP significantly in neuronal culture cells. A chemical
      chaperone that assisted ER functions reduced the expression of CHOP induced by
      sevoflurane exposure. In an in vivo study, we observed that an enhanced
      expression of CHOP and significantly more apoptotic cells in the brains of
      homozygous mutant BiP fetuses compared with the wild type. Mouse embryonic
      fibroblasts derived from the mutant BiP mice also exhibited enhanced levels of
      CHOP and cleaved caspase-3 after sevoflurane exposure. CONCLUSIONS: Sevoflurane
      exposure may cause ER stress, which is tolerated to some extent in wild-type
      cells. When this tolerance is limited, like in cells with mutant BiP, the
      exposure leads to cell death in the brain, suggesting that ER stress may
      partially mediate neurotoxicity caused by inhaled anesthetics. This study
      suggests that patients with certain conditions sensitive to ER stress such as
      ischemia, hypoxia, developing brain, or neurodegenerative diseases may be
      vulnerable to inhaled anesthetics.

PMID- 24108263
TI  - Selection of obese patients undergoing ambulatory surgery: a systematic review of
      the literature.
AB  - BACKGROUND: The incidence of obesity has increased over the past 2 decades. In
      recent years, several studies have assessed perioperative outcomes in obese
      patients undergoing ambulatory surgery. However, this evidence has not been
      reviewed and evaluated systematically. METHODS: We conducted a systematic review
      of studies published between 1948 and May 2012, assessing perioperative outcome
      in adult obese patients undergoing ambulatory surgery. All studies were eligible
      for inclusion if they reported perioperative complications including unplanned
      hospital admission and readmission. RESULTS: A literature search revealed 23
      studies (13 prospective and 10 retrospective), and 1 systematic review assessing
      laparoscopic bariatric surgery. A total of 106,119 patients were included in the
      analysis with 62,476 patients included in the prospective trials and 43,643
      patients included in the retrospective trials (not including the systematic
      review of laparoscopic bariatric surgery). Of these, 39,548 patients underwent
      bariatric surgery. The super obese (body mass index [BMI] >50 kg/m) appear to be
      at higher risk of complications. Patients undergoing nonbariatric surgery had a
      lower degree of obesity (BMI approximately 30 kg/m). Patients undergoing
      bariatric surgery were morbidly obese (BMI >40 kg/m), which is associated with a
      higher comorbidity burden. However, the lack of increase in unanticipated
      admission rate in this patient population may be related to thorough preoperative
      assessment and avoidance of patients with comorbid conditions. DISCUSSION: The
      literature lacks adequate information to make strong recommendations regarding
      appropriate selection of the obese patients scheduled for ambulatory surgery. The
      literature does indicate that the super obese (BMI >50 kg/ m) do present an
      increased risk for perioperative complications, while patient with lower BMIs do
      not seem to present any increased risk as long as any comorbidities are minimal
      or optimized before surgery. This review also identifies knowledge gaps and
      recommends future research required to guide optimal selection of obese patients
      scheduled for ambulatory surgery.

PMID- 24108264
TI  - Integrated proteomic and metabolomic analysis reveals the NADH-mediated TCA cycle
      and energy metabolism disorders based on a new model of chronic progressive heart
      failure.
AB  - BACKGROUND: Despite major advances in the treatment of heart failure (HF), it
      remains the major cause of mortality and morbidity worldwide. Experimental models
      of HF typically utilize acute myocardial infarction. However, the majority of
      clinical HFs occur gradually by a chronic progressive mechanism. Thus, more
      relevant models are required to aid identification, quantification, and
      characterization of HF, and its underlying mechanisms. METHODS AND FINDINGS: We
      developed a model of progressive chronic heart failure (CHF) in the mini-swine by
      placement of an ameroid constrictor on the left anterior descending coronary
      artery (LAD). This model demonstrated a steady decline in the cardiac function
      from 8 to 12 weeks, with a 50% reduction in the ejection fraction. Further, the
      proteomic, metabolomic and bioinformatic analyses of ischemic tissue and plasma
      revealed a significant alteration of the mitochondrial respiratory chain mediated
      by nicotinamide adenine dinucleotide (NADH), which resulted in down-regulation of
      malate dehydrogenase (MDH) and insufficient energy supply to support cardiac
      contractility and relaxation. Furthermore, significant changes in apolipoprotein
      A-I, low density lipoprotein (LDL), and very LDL (VLDL) in plasma indicated that
      lipid metabolism disorders occurred in mini-swines with myocardial ischemia via
      glycerolipid metabolism. CONCLUSIONS: We describe a stable and easily
      reproducible CHF model using an ameroid constrictor placed on the LAD. We found
      that the NADH-mediated tricarboxylic acid cycle and energy metabolism disorders
      are key pathophysiological mechanisms underlying CHF. These data will provide
      potential biomarkers for monitoring the therapeutic intervention of CHF.

PMID- 24108265
TI  - Managing uncertainty in couples living with atrial fibrillation.
AB  - BACKGROUND: Living with a chronic disease such as atrial fibrillation (AF) not
      only affects the patient but also has implications for the partner. There is a
      lack of research on couples living with AF and, in particular, how they
      experience and deal with the disease. OBJECTIVE: The aim of this study was to
      explore couples' main concerns when one of the spouses is afflicted with AF and
      how they continually handle it within their partner relationship. METHODS:
      Classical grounded theory was used throughout the study for data collection and
      analysis. Interviews were conducted with 12 couples (patient and partner
      together). There were follow-up interviews with 2 patients and 2 partners
      separately. RESULTS: Couples living with AF experience uncertainty as a common
      main concern. This uncertainty was fundamentally rooted in not knowing the cause
      of AF and apprehension about AF episodes. Couples managed this uncertainty by
      either explicitly sharing concerns related to AF or through implicitly sharing
      their concerns. Explicit sharing incorporated strategies of mutual collaboration
      and finding resemblance, whereas implicit sharing incorporated strategies of
      keeping distance and tacit understanding. Time since diagnosis and time being
      symptom-free were factors influencing afflicted couples' shifting between
      implicit and explicit sharing. CONCLUSIONS: Atrial fibrillation affects the
      partner relationship by bringing uncertainty into couples' daily lives. Even
      though this study shares similarities with previous studies on couples living
      with chronic disease, it contributes to the existing knowledge by presenting a
      set of strategies used by couples in managing uncertainty when living with AF.

PMID- 24108266
TI  - A survey of nurses' practices and perceptions of family-centered care in Ireland.
AB  - Family-centered care (FCC) is a philosophy of care that recognizes the family's
      central role in the child's life and in the delivery of care. We used a survey
      design to investigate the practices and perceptions of nurses toward FCC in
      Ireland. Data were obtained from 250 nurses in seven hospitals using the Family
      Centered Care Questionnaire-Revised (FCCQ-R). Findings indicated that nurses'
      practices were significantly different from their perceptions of FCC. Nurses with
      dual registration (children and adult) had significantly lower mean scores on the
      total current (practice) scale than the other registration subgroups. Nurses with
      a baccalaureate or a higher academic qualification had higher mean scores than
      nurses who held a certificate-level qualification on the total necessary
      (perception) scale, which assessed the activities perceived to be necessary for
      FCC. Findings showed that nurses support FCC but perceive the design of the
      health care system and parent-professional collaboration as barriers to FCC
      practice. 

PMID- 24108267
TI  - MOVER-R confidence intervals for ratios and products of two independently
      estimated quantities.

PMID- 24108268
TI  - Robust inference for mixed censored and binary response models with missing
      covariates.
AB  - In biomedical and epidemiological studies, often outcomes obtained are of mixed
      discrete and continuous in nature. Furthermore, due to some technical
      inconvenience or else, continuous responses are censored and also a few
      covariates cease to be observed completely. In this paper, we develop a model to
      tackle these complex situations. Our methodology is developed in a more general
      framework and provides a full-scale robust analysis of such complex models. The
      proposed robust maximum likelihood estimators of the model parameters are
      resistant to potential outliers in the data. We discuss the asymptotic properties
      of the robust estimators. To avoid computational difficulties involving
      irreducibly high-dimensional integrals, we propose a Monte Carlo method based on
      the Metropolis algorithm for approximating the robust maximum likelihood
      estimators. We study the empirical properties of these estimators in simulations.
      We also illustrate the proposed robust method using clustered data on blood sugar
      content from a clinical trial of individuals who were investigated for diabetes.

PMID- 24108270
TI  - Longitudinal prostate-specific antigen reference ranges: Choosing the underlying
      model of age-related changes.
AB  - Serial measurements of prostate-specific antigen (PSA) are used as a biomarker
      for men diagnosed with prostate cancer following an active monitoring programme.
      Distinguishing pathological changes from natural age-related changes is not
      straightforward. Here, we compare four approaches to modelling age-related change
      in PSA with the aim of developing reference ranges for repeated measures of PSA.
      A suitable model for PSA reference ranges must satisfy two criteria. First, it
      must offer an accurate description of the trend of PSA on average and in
      individuals. Second, it must be able to make accurate predictions about new PSA
      observations for an individual and about the entire PSA trajectory for a new
      individual.

PMID- 24108269
TI  - Linear spline multilevel models for summarising childhood growth trajectories: A
      guide to their application using examples from five birth cohorts.
AB  - Childhood growth is of interest in medical research concerned with determinants
      and consequences of variation from healthy growth and development. Linear spline
      multilevel modelling is a useful approach for deriving individual summary
      measures of growth, which overcomes several data issues (co-linearity of repeat
      measures, the requirement for all individuals to be measured at the same ages and
      bias due to missing data). Here, we outline the application of this methodology
      to model individual trajectories of length/height and weight, drawing on examples
      from five cohorts from different generations and different geographical regions
      with varying levels of economic development. We describe the unique features of
      the data within each cohort that have implications for the application of linear
      spline multilevel models, for example, differences in the density and inter
      individual variation in measurement occasions, and multiple sources of
      measurement with varying measurement error. After providing example Stata syntax
      and a suggested workflow for the implementation of linear spline multilevel
      models, we conclude with a discussion of the advantages and disadvantages of the
      linear spline approach compared with other growth modelling methods such as
      fractional polynomials, more complex spline functions and other non-linear
      models.

PMID- 24108271
TI  - Item response theory and structural equation modelling for ordinal data:
      Describing the relationship between KIDSCREEN and Life-H.
AB  - Both item response theory and structural equation models are useful in the
      analysis of ordered categorical responses from health assessment questionnaires.
      We highlight the advantages and disadvantages of the item response theory and
      structural equation modelling approaches to modelling ordinal data, from within a
      community health setting. Using data from the SPARCLE project focussing on
      children with cerebral palsy, this paper investigates the relationship between
      two ordinal rating scales, the KIDSCREEN, which measures quality-of-life, and
      Life-H, which measures participation. Practical issues relating to fitting
      models, such as non-positive definite observed or fitted correlation matrices,
      and approaches to assessing model fit are discussed. item response theory models
      allow properties such as the conditional independence of particular domains of a
      measurement instrument to be assessed. When, as with the SPARCLE data, the latent
      traits are multidimensional, structural equation models generally provide a much
      more convenient modelling framework.

PMID- 24108272
TI  - Studying noncollapsibility of the odds ratio with marginal structural and
      logistic regression models.
AB  - One approach to quantifying the magnitude of confounding in observational studies
      is to compare estimates with and without adjustment for a covariate, but this
      strategy is known to be defective for noncollapsible measures such as the odds
      ratio. Comparing estimates from marginal structural and standard logistic
      regression models, the total difference between crude and conditional effects can
      be decomposed into the sum of a noncollapsibility effect and confounding bias. We
      provide an analytic approach to assess the noncollapsibility effect in a point
      exposure study and provide a general formula for expressing the noncollapsibility
      effect. Next, we provide a graphical approach that illustrates the relationship
      between the noncollapsibility effect and the baseline risk, and reveals the
      behavior of the noncollapsibility effect for a range of different exposure and
      covariate effects. Various observations about noncollapsibility can be made from
      the different scenarios with or without confounding; for example, the magnitude
      of effect of the covariate plays a more important role in the noncollapsibility
      effect than does that of the effect of the exposure. In order to explore the
      noncollapsibility effect of the odds ratio in the presence of time-varying
      confounding, we simulated an observational cohort study. The magnitude of
      noncollapsibility was generally comparable to the effect in the point-exposure
      study in our simulation settings. Finally, in an applied example we demonstrate
      that collapsibility can have an important impact on estimation in practice.

PMID- 24108273
TI  - RelB and the aryl hydrocarbon receptor: dendritic cell tolerance at the
      epithelial interface.

PMID- 24108274
TI  - The perceptions of UK youth of branded and standardized, 'plain' cigarette
      packaging.
AB  - BACKGROUND: Tobacco packaging is an important form of promotion. Standardizing
      cigarette packages ('plain' packaging) represents a novel tobacco control policy.
      This study examined perceptions of branded and standardized cigarette packages
      among British youth. METHODS: Seven hundred twelve youth aged 11-17 completed an
      online survey. Participants viewed pairs of packages altered using a 3 * 2
      factorial design: health warning type (40% text, 40% pictorial or 80% pictorial)
      * standardized pack colour (white vs. brown). A discrete-choice task was used in
      which participants selected packs based on attractiveness, taste, tar, health
      risk, impact of health warning and enticement to start smoking. Participants also
      compared regular Silk Cut and 'Superslims' Silk Cut packs. Participants completed
      a final selection task from two standardized and two branded packs. RESULTS:
      Warning type was significantly associated with all six outcomes: packs with
      larger pictorial warnings were more likely to be perceived as less attractive,
      less smooth, greater health risk, higher tar delivery, more effective health
      warnings and less likely to encourage initiation. The same pattern was found for
      brown vs. white standardized packages, with the exception of attractiveness and
      initiation. Compared with the regular Silk Cut pack, the 'Superslims' Silk Cut
      pack was perceived as significantly more favourable on all six outcomes. Finally,
      among respondents who selected a pack in the pack selection task, 95.1% selected
      a branded pack vs. 4.9% who selected a standardized pack. CONCLUSIONS: Increasing
      the size of pictorial health warnings and standardizing the appearance and shape
      of packages may discourage smoking initiation among young people.

PMID- 24108275
TI  - Oxidation of water by a nonhaem diiron(IV) complex via proton-coupled electron
      transfer.
AB  - A high-potential nonhaem (MU-oxo)diiron(IV) complex was found to oxidize water to
      a hydroxyl radical via PCET, instead of forming an O-O bond. The rate-determining
      step requires a second water molecule, proposed to act as a base to promote
      proton transfer. This work shows that additional factors besides a high redox
      potential are required to effect O-O bond formation.

PMID- 24108276
TI  - DNA-based highly tunable particle focuser.
AB  - DNA is distinguished by both long length and structural rigidity. Classical
      polymer theories predict that DNA enhances the non-Newtonian elastic properties
      of its dilute solution more significantly than common synthetic flexible polymers
      because of its larger size and longer relaxation time. Here we exploit this
      property to report that under Poiseuille microflow, rigid spherical particles
      laterally migrate and form a tightly focused stream in an extremely dilute DNA
      solution (0.0005 (w/v)%). By the use of the DNA solution, we achieve highly
      efficient focusing (>99.5%) over an unprecedented wide range of flow rates (ratio
      of maximum to minimum flow rates ~400). This highly tunable particle-focusing
      technique can be used in the design of cost-effective portable flow cytometers,
      high-throughput cell analysis and also for cell sorting by size. We demonstrate
      that DNA is an efficient elasticity enhancer, which originates from its unique
      structural properties. 

PMID- 24108277
TI  - Femoral nerve strain at L4-L5 is minimized by hip flexion and increased by table
      break when performing lateral interbody fusion.
AB  - STUDY DESIGN: Anatomic studies have demonstrated that nerves and blood vessels
      have excursion with extremity range of motion. We have measured femoral nerve
      excursion with the lateral lumbar transpsoas interbody fusion (LLIF) procedure
      with changes in table flexion and ipsilateral hip flexion on both sides of 5
      cadavers. OBJECTIVE: To determine the effect of hip range of motion on femoral
      nerve strain near the L4-L5 disc space because it pertains to the LLIF procedure.
      SUMMARY OF BACKGROUND DATA: Postoperative thigh symptoms are common after the
      LLIF procedure. Although nerve strain in general has been shown to impair
      function, it has not been tested specifically with LLIF. METHODS: Five cadavers
      were placed in the lateral position as though undergoing the L4-L5 LLIF
      procedure. Radiographical markers were implanted into the femoral nerve. Lateral
      and anteroposterior fluoroscopic images were recorded with 0 degrees  initial
      table flexion and the hip at 0, 20, 40, and 60 degrees  flexion. The table was
      flexed to 40 degrees , and the process repeated. Examination was repeated on the
      contralateral side and nerve strain and excursion were calculated. RESULTS: Table
      flexion results in preloading the femoral nerve when approaching L4-L5. Nerve
      strain was highest with the table flexed to 40 degrees  and the hip at 0 degrees 
      (average, 6%-7%). Strain in the femoral nerve decreased with increasing hip
      flexion for both table flexion angles. Anterior displacement of the nerve by
      approximately 1.5 mm was noted at 40 degrees  table flexion compared with 0
      degrees . CONCLUSION: Strain values with table flexion of 40 degrees  approached
      those associated with reduced neural blood flow in animal studies. Table flexion
      should be minimized to the extent possible when performing L4-L5 LLIF.
      Additionally, hip flexion to 60 degrees  can neutralize the neural strain that
      occurs with aggressive table flexion. LEVEL OF EVIDENCE: N/A.

PMID- 24108280
TI  - Comparison of TLIF with rhBMP-2 versus no TLIF and higher posterolateral rhBMP-2
      dose at L5-S1 for long fusions to the sacrum with sacropelvic fixation in
      patients with primary adult deformity.
AB  - STUDY DESIGN: Comparvative case series. Data was prospectively entered and
      retrospectively analyzed. OBJECTIVE: To evaluate the need for distal lumbar
      interbody fusion when sufficient recombinant human bone morphogenetic protein-2
      (rhBMP-2) is used posterolaterally at L5-S1 in long spinal constructs for adult
      deformity via costs and radiographical and patient-reported outcome comparisons.
      SUMMARY OF BACKGROUND DATA: Many authors and investigators have suggested that an
      interbody fusion is mandatory at L5-S1 with long fusion to the sacrum with
      sacropelvic fixation. Past studies have shown competitive fusion rates using
      rhBMP-2 versus iliac crest bone graft for long fusions. There are various
      advocates for anterior lumbar interbody fusion versus posterior lumbar interbody
      fusion versus transforaminal lumbar interbody fusion (TLIF). The optimal strategy
      remains elusive. METHODS: Fifty-seven patients were studied at one institution.
      Thirty-one patients had no interbody fusion (NI group) with 20 mg of rhBMP-2
      posterolaterally on 10 mL of carrier and 26 patients had TLIF at L5-S1 (TLIF
      group) with 6 mg of rhBMP-2 in the interbody space along with local bone graft
      and 6 mg of rhBMP-2 on carrier posterolaterally at L5-S1. Patients were followed
      for 24 to 87 months (mean follow-up, 3.92 yr). Demographics of the 2 groups were
      similar. RESULTS: There were no detected nonunions at L5-S1 in either group. By
      our limited cost analysis, the expense of performing a TLIF at L5-S1 is higher
      than that of using extra rhBMP-2 posterolaterally at that segment. Improvement in
      outcomes scores, namely Scoliosis Research Society-22 and Oswestry Disability
      Index, were the same statistically in both groups. Blood loss was greater in the
      TLIF group than the NI group. There were no identified rhBMP-2 adverse events in
      either group. CONCLUSION: Utilization of 20 mg of rhBMP-2 at L5-S1 has the
      potential to be less expensive than an interbody fusion in most patients having a
      primary long fusion for adult spinal deformity. The apparent fusion rates at L5
      S1 were identical in both groups. Both strategies were successful in regard to
      improving patient outcomes and achieving apparent solid arthrodesis at the
      lumbosacral junction, which was the focus of this study. LEVEL OF EVIDENCE: 2.

PMID- 24108282
TI  - In response.

PMID- 24108283
TI  - Expectation of recovery from low back pain: a longitudinal cohort study
      investigating patient characteristics related to expectations and the association
      between expectations and 3-month outcome.
AB  - STUDY DESIGN: A prospective cohort study conducted in general practice (GP) and
      chiropractic practice (CP). OBJECTIVE: To explore which patient characteristics
      were associated with recovery expectations in patients with low back pain (LBP),
      whether expectations predicted 3-month outcome, and to what extent expectations
      were associated with empirical prognostic factors. SUMMARY OF BACKGROUND DATA:
      Patients' recovery expectations have been associated with prognosis, but it is
      largely unknown why patients expect what they do, and how expectations relate to
      other prognostic factors. METHODS: A total of 1169 participants completed
      questionnaires at their first consultation due to LBP, and 78% were followed for
      3 months. At baseline, recovery expectations were measured on a 0 to 10 scale.
      Outcome measures were LBP intensity and global perceived effect. Associations
      were tested in regression models, and the predictive capacity of expectations
      described in terms of adjusted R and area under the receiver operating
      characteristic curve. Correlations between predicted expectations and prognosis
      were quantified by the Spearman rho. RESULTS: Expectations were associated with
      known prognostic factors, mainly LBP history, but were only partly explained by
      measured factors (adjusted R, 35% [CP]/55% [GP]). Expectations had statistically
      significant associations with both outcomes after adjusting for other baseline
      factors, but explained only a little of the variance in LBP (adjusted R: 0.11
      CP/0.32 GP) and did not add to the explained variance. The prediction of global
      perceived effect was limited in CP (area under the receiver operating
      characteristics curve, 0.59), but more substantial in GP (area under the receiver
      operating characteristics curve, 0.77) patients. Correlations between predicted
      expectations and predicted outcome were strong. CONCLUSION: Patients' recovery
      expectations were associated mainly with LBP history and were generally, but not
      consistently, similar to an empirically predicted prognosis. Expectations were
      significantly associated with outcome, and may, at least for some outcomes, be a
      relevant proxy for more complex models. Future studies should explore the effect
      of addressing negative recovery expectations. LEVEL OF EVIDENCE: 2.

PMID- 24108284
TI  - Osteoblastoma of the sacrum: report of 18 cases and analysis of the literature.
AB  - STUDY DESIGN: Retrospective case series. OBJECTIVE: (1) To analyze clinical and
      radiographical characteristics, treatment, and outcome in patients with sacral
      osteoblastoma, (2) to evaluate progression-free survival and local recurrence
      rate, and (3) to identify prognostic factors. SUMMARY OF BACKGROUND DATA:
      Osteoblastoma is a rare tumor that has been reported to affect the sacrum from 7%
      to 17%. Symptoms are various and the diagnosis is often delayed. METHODS: From
      1980 to 2010, 18 patients with sacral osteoblastoma (16 males and 2 females) were
      treated at Rizzoli Institute. Lesion involved S1 (2 cases), S1-S2 (3 cases), S2
      (1 case), S2-S3 (1 case), S2-S4 (1 case), S3 (2 cases), S3-S4 (5 cases), S4 (1
      case), and almost the entire sacrum in 2 cases. According to Enneking
      classification for benign bone tumors, 13 (72%) were diagnosed at stage 2 and 5
      (28%) at stage 3. Mean tumor volume was 64 cm (range, 2-441 cm). Nine patients
      had preoperative magnetic resonance imaging. Five patients had a previous
      inadequate intralesional surgery elsewhere. Treatment consisted in intralesional
      surgery (16 cases), intralesional surgery and radiotherapy (1 case), and wide
      resection (1 case). Local adjuvants used were phenol (7 patients),
      cryocoagulation with "iceball" technique (1 case). Embolizations were performed
      in 7 patients. RESULTS: At a mean of 8.4 years (range, 1-28 yr), 15 patients
      (83%) remained continuously disease free, whereas 3 patients had local recurrence
      (17%). Progression-free survival was 87% at 5 years and 74% at 10 years. No
      statistical difference was found between patients who received or not local
      adjuvants (P = 1.254), older or younger than 20 years (P = 0.970), at stage 2 or
      3 (P = 0.826), evaluated preoperatively with or without magnetic resonance
      imaging (P = 0.160), primarily treated versus patients with previous
      intralesional surgery elsewhere (P = 0.131). CONCLUSION: In our series, curettage
      was successful in most of the patients. Local adjuvants did not seem to reduce
      the risk of local recurrence when combined with intralesional surgery. LEVEL OF
      EVIDENCE: 4.

PMID- 24108285
TI  - Prediction of thoracic dimensions and spine length on the basis of individual
      pelvic dimensions: validation of the use of pelvic inlet width obtained by
      radiographs compared with computed tomography.
AB  - STUDY DESIGN: Retrospective review. OBJECTIVE: To validate the pelvic inlet width
      (PIW) measurement obtained on radiograph as an independent standard used to
      correlate with thoracic dimensions (TDs) in treated and untreated patients with
      early-onset scoliosis. SUMMARY OF BACKGROUND DATA: In children with early-onset
      scoliosis, the change in TD and spine length is a key treatment goal. Quantifying
      this change is confounded by varied growth rates and differing diagnoses. PIW
      measured on computed tomographic (CT) scan in patients without scoliosis has been
      shown to correlate with TD in an age-independent manner. METHODS: The first arm
      included 49 patients with scoliosis who had both a CT scan and pelvic radiograph.
      Agreement between PIW measurements on CT scan and radiograph was analyzed. The
      second arm consisted of 163 patients (age, 0.2-18.7 yr), with minimal spinal
      deformity (mean Cobb, 9.0 degrees ) and radiographs in which PIW was measurable.
      PIW was compared with previously published CT-based TD measurements; maximal
      chest width, T1-T12 height, and T1-S1 height. Linear regression analysis was used
      to develop and validate sex-specific predictive equations for each TD measurement
      on the basis of PIW. Interobserver reliability was evaluated for all
      measurements. RESULTS: Bland-Altman analysis indicated agreement with no
      dependence on observed value, but a consistent 8.5 mm (95% CI: 7.2-9.9 mm)
      difference in CT scan measurement compared with radiographical PIW measurement.
      Sex and PIW were significantly correlated to each TD measurement (P < 0.01).
      Predictive models were validated and may be used to estimate TD measurements on
      the basis of sex and radiographical PIW. Intraclass correlation coefficients for
      all measurements were between 0.978 and 0.997. CONCLUSION: PIW on radiographs and
      CT scan correlate in patients with deformity and with spine and TD in patients
      with minimal deformity. It is a fast, reliable method of assessing growth while
      lowering patient's radiation exposure. It can be reliably used to assess patients
      with early-onset scoliosis and the impact surgical treatment has on chest and
      spinal growth. LEVEL OF EVIDENCE: 3.

PMID- 24108286
TI  - Validity and reliability of the French version of the STarT Back screening tool
      for patients with low back pain.
AB  - STUDY DESIGN: Observational prospective study. OBJECTIVE: Our objective was to
      assess the reliability and validity of the French version of the Keele STarT Back
      Screening Tool (SBST). SUMMARY OF BACKGROUND DATA: The SBST is a recently
      validated tool developed to identify subgroups of patients with low back pain
      (LBP) to guide early secondary prevention in primary care. METHODS: Outpatients
      18 years or older with LBP, attending a rehabilitation center, a back school, a
      private physiotherapy unit, or a fitness center were included. Patients were
      assessed through the SBST, Roland-Morris Disability Questionnaire, Orebro
      Musculoskeletal Pain Screening Questionnaire, Medical Outcomes Survey Short Form
      36 questionnaire, and a pain visual analogue scale. Test-retest reliability was
      assessed with Kappa score or the intraclass correlation coefficient, internal
      consistency of the Psychological subscale with the Cronbach alpha coefficient,
      construct validity with the Spearman correlation coefficient, and floor and
      ceiling effects by percentage frequency of lowest or highest possible score
      achieved by respondents. RESULTS: One hundred eight patients with LBP were
      included. The test-retest reliability of the SBST total score was excellent with
      an intraclass correlation coefficient of 0.90 (0.81-0.95). The Cronbach alpha
      coefficient was 0.73 showing a good internal consistency for the Psychological
      subscale. High Spearman correlation coefficients of 0.74 between SBST and Roland
      Morris Disability Questionnaire, and 0.74 between the SBST and Orebro
      Musculoskeletal Pain Screening Questionnaire were observed. As expected, low-to
      moderate correlations were observed between the SBST total score and some
      dissimilar measures of the Short-Form 36. The lowest possible SBST score was
      observed for 8 patients (7.4%), whereas only 3 patients (2.8%) had the highest
      possible SBST score. CONCLUSION: The French version of the SBST is a reliable and
      valid questionnaire consistent with the original English version. Therefore, this
      new version may help French-speaking clinicians and scientists to stratify
      patients with LBP. LEVEL OF EVIDENCE: 2.

PMID- 24108287
TI  - Progressive kyphosis after vertebroplasty in osteoporotic vertebral compression
      fracture.
AB  - STUDY DESIGN: A single-center retrospective study. OBJECTIVE: To identify the
      relevant incidence and risk factors of delayed vertebral collapse and progressive
      kyphosis with spinal canal encroachment after percutaneous vertebroplasty (PVP)
      for vertebral compression fracture (VCF). SUMMARY OF BACKGROUND DATA: Delayed
      vertebral collapse and progressive kyphosis with spinal canal encroachment are
      complications after PVP for VCF. METHODS: Between December 2002 and February
      2011, 843 patients underwent PVP for VCFs for at least 2 years of minimum follow
      up term in a tertiary referral center. All imaging measurements were obtained
      digitally, with comparisons of the Cobb angle and spinal canal stenosis on
      fractured vertebral level at 3 different time points of pre- and
      postvertebroplasty, and before revision surgery. RESULTS: Thirteen patients (14
      fractures) who underwent PVP had delayed vertebral collapse and progressive
      kyphosis on the level of the fractured vertebra, 3 were male and 10 female, with
      a median age of 75 years (range, 66-89 yr). One had 2-level VCFs. All were
      treated with revision surgery of decompressive laminectomy for spinal canal
      stenosis with neurological complications. Twelve patients had additional
      instrument fixation. The involved vertebras were concentrated at the
      thoracolumbar junction region (T11-L2). The mean Cobb angles were measured at
      23.67 degrees  before PVP, 15.90 degrees  after PVP, and 30.92 degrees  before
      revision surgery. The ratio of spinal canal stenosis was 35.45% and 49.48% before
      PVP and revision surgery, respectively. The occurrence rate of delayed
      complications was about 1.5% (13/843). CONCLUSION: Conservative treatment and
      minimal invasive vertebral augmentation surgery can be selected from patients
      with stable VCFs. Close follow-up is warrant to monitor the occurrence of late
      collapse with neurological complications. LEVEL OF EVIDENCE: N/A.

PMID- 24108288
TI  - Psychiatric disorders and major spine surgery: epidemiology and perioperative
      outcomes.
AB  - STUDY DESIGN: Analysis of the National Hospital Discharge Survey database from
      1990 to 2007. OBJECTIVE: To evaluate the influence of preoperative depression,
      anxiety, schizophrenia, or dementia on in-hospital (1) adverse events, (2)
      mortality, and (3) nonroutine discharge in patients undergoing major spine
      surgery. SUMMARY OF BACKGROUND DATA: Psychiatric comorbidity is a known risk
      factor for impaired health-related quality of life and poor long-term outcomes
      after spine surgery, yet little is known about its impact in the perioperative
      spine surgery setting. METHODS: Using the National Hospital Discharge Survey
      database, all patients undergoing either spinal fusion or laminectomy between
      1990 and 2007 were identified and separated into groups with and without
      psychiatric disorders. Multivariable regression analysis was performed for each
      of the outcome variables. RESULTS: Between 1990 and 2007, a total estimated
      number of 5,382,343 spinal fusions and laminectomies were performed. The
      prevalence of diagnosed depression, anxiety, and schizophrenia among the study
      population increased significantly over time. Depression, anxiety, schizophrenia,
      and dementia were associated with higher rates of nonroutine discharge.
      Depression, schizophrenia, and dementia were associated with higher rates of
      adverse events. Dementia was the only psychiatric disorder associated with a
      higher risk of in-hospital mortality. CONCLUSION: Patients with preoperative
      psychiatric disorders undergoing major spine surgery are at increased risk for
      perioperative adverse events and posthospitalization care, but its effect in
      perioperative mortality is more limited. Presurgical psychological screening of
      candidates undergoing spine surgery might ultimately lead to the enhancement of
      perioperative outcomes in this growing segment of the US population. LEVEL OF
      EVIDENCE: N/A.

PMID- 24108289
TI  - Anterior versus posterior surgical approaches to treat cervical spondylotic
      myelopathy: outcomes of the prospective multicenter AOSpine North America CSM
      study in 264 patients.
AB  - STUDY DESIGN: A prospective observational multicenter study. OBJECTIVE: To help
      solve the debate regarding whether the anterior or posterior surgical approach is
      optimal for patients with cervical spondylotic myelopathy (CSM). SUMMARY OF
      BACKGROUND DATA: The optimal surgical approach to treat CSM remains debated with
      varying opinions favoring anterior versus posterior surgical approaches. We
      present an analysis of a prospective observational multicenter study examining
      outcomes of surgical treatment for CSM. METHODS: A total of 278 subjects from 12
      sites in North America received anterior/posterior or combined surgery at the
      discretion of the surgeon. This study focused on subjects who had either anterior
      or posterior surgery (n = 264, follow-up rate, 87%). Outcome measures included
      the modified Japanese Orthopedic Assessment scale, the Nurick scale, the Neck
      Disability Index, and the Short-Form 36 (SF-36) Health Survey version 2 Physical
      and Mental Component Scores. RESULTS: One hundred and sixty-nine patients were
      treated anteriorly and 95 underwent posterior surgery. Anterior surgical cases
      were younger and had less severe myelopathy as assessed by mJOA and Nurick
      scores. There were no baseline differences in Neck Disability Index or SF-36
      between the anterior and posterior cases. Improvement in the mJOA was
      significantly lower in the anterior group than posterior group (2.47 vs. 3.62,
      respectively, P < 0.01), although the groups started at different levels of
      baseline impairment. The extent of improvement in the Nurick Scale, Neck
      Disability Index, SF-36 version 2 Physical Component Score, and SF-36 version 2
      Mental Component Score did not differ between the groups. CONCLUSION: Patients
      with CSM show significant improvements in several health-related outcome measures
      with either anterior or posterior surgery. Importantly, patients treated with
      anterior techniques were younger, with less severe impairment and more focal
      pathology. We demonstrate for the first time that, when patient and disease
      factors are controlled for, anterior and posterior surgical techniques have
      equivalent efficacy in the treatment of CSM. LEVEL OF EVIDENCE: 3.

PMID- 24108290
TI  - Surgical strategy and management outcomes for adjacent multisegmental spinal
      tuberculosis: a retrospective study of forty-eight patients.
AB  - STUDY DESIGN: Retrospective study. OBJECTIVE: To evaluate the clinical outcomes
      of 4 different procedures for the treatment of adjacent multisegmental spinal
      tuberculosis (AMSST) and to investigate the selection strategy of the optimal
      procedure with respect to focal characteristics. SUMMARY OF BACKGROUND DATA:
      Because of the lack of support of the anterior columns of multiple segments,
      AMSST is thought to confer high risks for the development of kyphosis and
      paraplegia. However, there are few reports regarding the clinical outcomes of the
      surgical treatment for AMSST have been investigated. METHODS: From August 1999 to
      June 2010, 48 patients with AMSST were enrolled in this study. Seven patients (A
      group) underwent a single-stage anterior operation. Eighteen patients (AP group)
      underwent a single-stage posterior and anterior combined operation. Eighteen
      patients (P group) underwent a single-stage posterior operation. Five patients
      (DP group) underwent computed tomography-guided drainage and local chemotherapy
      combined with a 2-stage posterior operation. The patients were followed up
      clinically and radiologically for an average of 29.6 months. RESULTS: The cohort
      consisted of 29 males and 19 females, aged 4 to 54 years. The patients exhibited
      significant improvements in deformity and neurological deficits. Graft union was
      achieved in all patients 5 to 12 months postoperatively. Surgery-related
      complications were noted in 1 and 2 patients in the AP and P groups,
      respectively. Postoperative recurrence occurred in 1 and 2 patients in the AP and
      P groups, respectively. All 48 patients had been cured at the final follow-up.
      CONCLUSION: This study demonstrated that the 4 procedures can safely and
      effectively achieve nerve decompression, graft fusion, and kyphosis correction.
      Individualized procedures should be chosen according to the patient's general
      condition, focal characteristic, type of complication, and surgeon's experience.
      LEVEL OF EVIDENCE: 3.

PMID- 24108291
TI  - Management of subaxial cervical facet dislocation through anterior approach
      monitored by spinal cord evoked potential.
AB  - STUDY DESIGN: Retrospective case series. OBJECTIVE: To discuss the clinical
      efficacy of anterior cervical surgery of decompression, reduction, stabilization,
      and fusion in treating subaxial cervical facet dislocation without spinal cord
      injury or with mild spinal cord injury monitored by spinal cord evoked potential.
      SUMMARY OF BACKGROUND DATA: The optimal treatment of lower cervical facet
      dislocation has been controversial. Because of the risk of iatrogenic damage of
      neurological function, it is challenging for surgeons to manage the lower
      cervical facet dislocation without or with mild spinal cord injury. To avoid the
      risks, more secure strategy need to be designed. METHODS: A retrospective study
      was performed on 17 cases of subaxial cervical facet dislocation without spinal
      cord injury or with mild spinal cord injury treated by anterior cervical surgery
      under spinal cord evoked potential monitor from January 2008 to June 2012. There
      were 12 males, 5 females, with a mean age of 40.1 years (from 21 to 73 yr).
      Dislocation sites: 1 in C3-C4, 2 in C4-C5, 6 in C5-C6, 8 in C6-C7; 10 cases with
      unilateral cervical facet dislocation, 7 cases with bilateral dislocation.
      Thirteen patients were preoperatively classified as grade D and 4 as E according
      to Frankel standard. All patients were followed up for average of 16 months.
      RESULTS: All operations were completed successfully. Postoperative radiographs
      showed that the sequence and curvature of the cervical spine were well recovered.
      And, evidence of intervertebral fusion was observed at 3 months in all cases. No
      redislocation or symptoms of spinal cord injury occurred. Thirteen cases with
      mild spinal cord injury recovered at 1 month after operation. CONCLUSION:
      Anterior cervical surgery of decompression, reduction, stabilization, and fusion
      monitored by spinal cord evoked potential is an effective and safe method for
      treatment of subaxial cervical facet dislocation without or with mild spinal cord
      injury. LEVEL OF EVIDENCE: 4.

PMID- 24108292
TI  - Comparison between cervical total disc replacement and anterior cervical
      discectomy and fusion of 1 to 2 levels from 2002 to 2009.
AB  - STUDY DESIGN: Retrospective database analysis. OBJECTIVE: To compare the
      perioperative patient characteristics, early postoperative outcomes, and costs
      between anterior cervical discectomy and fusion (ACDF) and cervical total disc
      replacement (TDR) in the United States. SUMMARY OF BACKGROUND DATA: Cervical TDR
      and ACDF are indicated to treat symptomatic cervical degenerative pathology. The
      epidemiology, complication rates, and the cost differences between the 2 surgical
      approaches are not well characterized. METHODS: Data from the Nationwide
      Inpatient Sample of the Healthcare Cost and Utilization Project was queried from
      2002 to 2009. Patients undergoing cervical TDR or ACDF of 1 to 2 levels were
      identified. Patient demographics, comorbidities, length of stay, costs, and the
      in-hospital complications were assessed. SPSS (version 20) was used for
      statistical analysis with chi test for categorical data and independent-samples t
      test for continuous data. A value of P <= 0.001 denoted statistical significance.
      Multinomial regression analysis was used to identify the independent risk for
      complications in the TDR cohort compared with the ACDF cohort. RESULTS: There
      were 141,230 ACDF cases of 1 to 2 levels and 1830 cervical TDR cases identified
      in the Nationwide Inpatient Sample database. The ACDF cohort was older and
      demonstrated a greater comorbidity burden than the TDR group (P < 0.001). The
      ACDF-treated patients demonstrated a significantly greater length of stay than
      the TDR group (P < 0.001). In contrast, there were no significant differences in
      the incidence of postoperative complications, mortality, or hospital costs
      between the surgical cohorts. Multinomial regression did not demonstrate
      significant differences in the risk for postoperative complications between the
      surgical techniques. CONCLUSION: The ACDF cohort was significantly older and
      demonstrated a greater comorbidity burden that likely contributed to the greater
      length of stay when than the TDR cohort. Both cohorts demonstrated comparable
      incidences of early postoperative complications and costs. There were no
      significant differences in the risks for postoperative complications between the
      surgical cohorts. Further studies are warranted to characterize the long-term
      complications, costs, and patient outcomes between the 2 surgical techniques.
      LEVEL OF EVIDENCE: 3.

PMID- 24108293
TI  - Long-term results of cervical myelopathy due to ossification of the posterior
      longitudinal ligament with an occupying ratio of 60% or more.
AB  - STUDY DESIGN: Retrospective study. OBJECTIVE: We sought to determine the long
      term outcomes of laminoplasty versus anterior decompression and fusion in the
      treatment of cervical myelopathy caused by ossification of the posterior
      longitudinal ligament (OPLL) and to ascertain what factors should be considered
      in selecting appropriate surgical procedure. SUMMARY OF BACKGROUND DATA: There
      are little data about long-term results of cervical myelopathy due to OPLL with
      an occupying ratio 60% or more. METHODS: We retrospectively studied 27 patients
      having OPLL with an occupying ratio 60% or more and a follow-up period of at
      least 2 years. Clinical outcome was evaluated using Japanese Orthopaedic
      Association scores and recovery rates (>=75%, excellent; 50%-74%, good; 25%-50%,
      fair; and <25%, poor). RESULTS: The mean age and the mean duration of follow-up
      were 57 years and 10.2 years. The mean Japanese Orthopaedic Association score was
      9.3 before surgery and 12.4 at the final follow-up examination. There were 15
      patients in the laminoplasty group (LAM group) and 12 patients in the anterior
      decompression and fusion group (ADF group). The ADF group had a significantly
      better recovery rate at final evaluation (53% vs. 30%; P = 0.04), a longer
      duration of surgery (314 vs. 128 min; P < 0.01), and greater blood loss (600 vs.
      240 mL; P < 0.01) than did the LAM group. In the LAM group, 4 patients with
      excellent or good results had a significantly larger degree of cervical lordosis
      (30 degrees vs. 10 degrees ; P = 0.002) than others. CONCLUSION: The ADF group
      had a significantly better recovery rate than the LAM group, although the degree
      of surgical invasiveness was high. ADF is generally recommended for OPLL with an
      occupying ratio 60% or more. LEVEL OF EVIDENCE: 3.

PMID- 24108294
TI  - Comprehensive vertebral deformity and vertebral fracture assessment in clinical
      practice: intra- and inter-reader agreement of a clinical workflow tool.
AB  - STUDY DESIGN: Study design randomized intra- and inter-reader reproducibility
      study. OBJECTIVE: To evaluate reproducibility of quantitative morphometry (QM)
      and agreement of dichotomous fracture/no-fracture status on lateral spinal
      radiographs acquired during routine clinical practice using a clinical workflow
      tool. SUMMARY OF BACKGROUND DATA: Several recent guidelines have underlined the
      importance of Genant semi-quantitative scoring and selective QM to confirm and
      grade suspected vertebral fractures in clinical practice. METHODS: Thoracic and
      lumbar spine radiographs were acquired from 98 consecutive subjects (mean age,
      60.1 +/- 11.7 yr) attending the clinic for osteoporosis evaluation. For each
      subject, QM and Genant semi-quantitative scoring were performed on all evaluable
      vertebrae from L4 to T4 using a software workflow tool. A radiologist and an
      experienced radiographical technician performed 2 repeat reading sessions of the
      radiographs 12 months apart, blinded to each other's results; for the second
      read, the cases were anonymized and the order was randomized. RESULTS: Inter
      reader reproducibility results were 3.1% and 3.2% coefficient of variation (%)
      for heights, 0.030 and 0.031 root mean square standard deviation for height
      ratios. For intrareader reproducibility, these values were 2.2% and 3.5%
      coefficient of variation %; 0.023 and 0.034 root mean square standard deviation.
      Kappa score results for agreement of dichotomous fracture/no-fracture status were
      0.67 and 0.72 (inter-rater) and 0.50 and 0.67 (intrarater). CONCLUSION: The
      software assessed in this study is a reliable clinical tool that facilitates QM
      and Genant semi-quantitative scoring of the spine in routine clinical practice.
      LEVEL OF EVIDENCE: 3.

PMID- 24108296
TI  - Comparison of deferoxamine and methylprednisolone: protective effect of
      pharmacological agents on lipid peroxidation in spinal cord injury in rats.
AB  - STUDY DESIGN: Experimental study. OBJECTIVE: To investigate the protective effect
      of deferoxamine (DFO) administration in comparison with methylprednisolone (MP)
      on lipid peroxidation and antioxidants after spinal cord injury (SCI) in rats.
      SUMMARY OF BACKGROUND DATA: DFO is used for treating an iron-chelating agent,
      which is also used in the treatment of iron poisoning and thalassaemia. The
      neuroprotective effect of DFO was evaulated as a therapeutic agent for SCI.
      METHODS: Forty Wistar rats were randomly divided into 5 groups as sham
      laminectomy (n = 8), laminectomy with SCI (n = 8), laminectomy with SCI and 0.9%
      saline intraperitoneal (i.p.) (n = 8), laminectomy with SCI and 30 mg/kg MP i.p.
      (n = 8), and laminectomy with SCI and 30 mg/kg DFO i.p. (n = 8). Neurological
      deficits were examined 24 hours after trauma, and all rats were killed. Spinal
      cord segments were harvested for both biochemical and histopathological
      evaluation. RESULTS: At 24 hours post-SCI, whereas malondialdehyde levels were
      increased, superoxide dismutase, catalase, and glutathione peroxidase levels were
      decreased in groups I, II, and III. MP and DFO treatment decreased MDA levels and
      increased superoxide dismutase CAT, and glutathione peroxidase levels in control
      and study groups. There was no statistically significant difference between
      treatment with MP and DFO (P> 0.05). All rats were paraplegic after SCI, except
      in the sham group. Histopathological improvement was observed in control and
      study groups. CONCLUSION: This study indicates that beneficial effects may be
      provided and further studies need to investigate the dose-dependent beneficial
      and side effects of DFO in SCI. LEVEL OF EVIDENCE: N/A.

PMID- 24108297
TI  - Comparison of fatigue strength of C2 pedicle screws, C2 pars screws, and a hybrid
      construct in C1-C2 fixation.
AB  - STUDY DESIGN: A biomechanical study comparing the fatigue strength of different
      types of C2 fixation in a C1-C2 construct. OBJECTIVE: To determine the pullout
      strength of a C2 pedicle screw and C2 pars screw after cyclical testing and
      differentiate differences in stiffness pre- and post-cyclical loading of 3
      different C1-C2 fixations. SUMMARY OF BACKGROUND DATA: Some surgeons use a short
      C2 pars screw in a C1-C2 construct, because it is less technically demanding
      and/or when the vertebral artery is high riding. Difference in construct
      stiffness between use of bilateral C2 pedicle screws, bilateral C2 pars screws,
      or a hybrid construct is unknown. METHODS: Biomechanical testing was performed on
      15 specimens. A bicortical C1 lateral mass screw was used in combination with 1
      of 3 methods of C2 fixation: (1) bilateral long C2 pedicle screws (LL), (2)
      bilateral 14-mm C2 pars screws (SS), and (3) unilateral long C2 pedicle screw
      with a contralateral 14-mm C2 pars screw (LS). Each construct was subject to
      16,000 cycles to simulate the immediate postoperative period. Changes in motion
      in flexion-extension, lateral bending, and axial rotation were calculated. This
      was followed by pullout testing. RESULTS: The ability to limit range of motion
      significantly decreased after cyclical testing in flexion-extension, lateral
      bending, and axial rotation for all 3 groups. After loading, the LL and LS groups
      had less percentage of increase in motion in flexion-extension and lateral
      bending than the SS group. Overall, the average pullout strength of a pedicle
      screw was 92% stronger than a pars screw. CONCLUSION: C2 pedicle screws have
      twice the pullout strength of C2 pars screws after cyclical loading. In cases in
      which the anatomy limits placement of bilateral C2 pedicle screws, a construct
      using a unilateral C2 pedicle screw with a contralateral short pars screw is a
      viable option and compares favorably with a bilateral C2 pedicle screw construct.
      LEVEL OF EVIDENCE: N/A.

PMID- 24108298
TI  - Predictors of thirty-day readmission after anterior cervical fusion.
AB  - STUDY DESIGN: Retrospective cohort study. OBJECTIVE: To determine the incidence
      of and factors predicting 30-day readmission after anterior cervical discectomy
      and fusion (ACDF). SUMMARY OF BACKGROUND DATA: ACDF is being performed on an
      increasing basis on a wider population of patients, which is accompanied by
      rising costs. Readmissions have the potential to further deplete health care
      resources. Although past studies have shown that readmissions after surgery are
      driven by operative complications, specific predictors of readmission after ACDF
      are not well researched. METHODS: All patients who underwent ACDF or anterior
      corpectomy and fusion procedures in 2011 were selected from the American College
      of Surgeon's National Quality Improvement database. Readmissions were analyzed on
      the basis of demographics, comorbidities, operative characteristics, and
      complications were compared in univariate analyses. Multivariate logistic
      regression models were created to isolate the independent effects of preoperative
      and postoperative factors on readmission. RESULTS: The nationwide readmission
      rate after ACDF surgery in this study is 2.5%. Pulmonary complications (8.5%),
      wound complications (8.5%), and urinary tract infections (8.5%) are the most
      common complications seen in readmitted patients. Readmitted patients were
      significantly older (58 vs. 53, P = 0.003), with higher rates of diabetes and
      hypertension (28.8% vs. 13.9%, P = 0.001; 64.4% vs. 42.6%, P = 0.001,
      respectively). Although certain preoperative factors such as age 65 years or more
      and preoperative stay more than 24 hours increase the odds of operative
      complications (odds ratio, 3.5; 95% confidence interval, 2.0-6.0 and odds ratio,
      6.2; 95% confidence interval, 3.4-11.1, respectively), hypertension may
      independently increase the likelihood of readmission outside of any effect on
      complications (odds ratio, 1.8; 95% confidence interval, 1.0-3.4). CONCLUSION:
      The data in this study suggests that surgeons are already controlling readmission
      rates by limiting peri- and postoperative complications, but patients with a
      history of hypertension could have an increased likelihood of being readmitted
      despite avoiding a complication. LEVEL OF EVIDENCE: 3.

PMID- 24108299
TI  - Clinical results and functional outcomes after direct intralaminar screw repair
      of spondylolysis.
AB  - STUDY DESIGN: Prospective analysis. OBJECTIVE: Our objective was to analyze
      clinical and functional results of patients with spondylolysis treated via direct
      intralaminar screw fixation and autograft, a minimally invasive and motion
      preserving surgery. SUMMARY OF BACKGROUND DATA: Spondylolysis is usually treated
      nonoperatively; multiple surgical techniques are available when nonoperative
      measures fail. No studies evaluate the clinical and functional outcomes and their
      correlation with pars defect size and disc morphology on magnetic resonance
      imaging. METHODS: We reviewed patients with spondylolysis treated with
      intralaminar screw fixation and bone grafting from 2000 through 2010. Of the 31
      patients (mean age, 16 yr; range, 10-37 yr), 25 (81%) were competitive athletes.
      Preoperative computed tomographic scans were used to measure the pars defect
      size, and preoperative magnetic resonance images were graded using Pfirrmann
      classification for correlation with postoperative outcomes. Student t test was
      used for analysis (significance, P < 0.05). RESULTS: At a mean follow-up of 60
      months (range, 24-135 mo), pain (visual analogue scale score) significantly (P <
      0.01) improved: preoperative mean, 7 points (range, 1-10 points); postoperative
      mean, 2 points (range, 0-10 points). Of the 25 athletes, 19 (76%) returned to
      competitive sports with a mean postoperative visual analogue scale score of 1
      point (range, 0-4 points) at a mean of 6 months (range, 3-10 mo) after surgery.
      One patient required L6-S2 posterior spinal fusion after spondylolysis repair for
      persistent pain starting 18 months after intralaminar screw fixation, 2 patients
      sustained unilateral intralaminar screw fractures at L5, and 1 patient required
      irrigation and debridement for a superficial postoperative infection. There was
      no correlation among preoperative magnetic resonance imaging disc morphology,
      defect size on computed tomography, patient age, and clinical outcomes.
      CONCLUSION: Direct repair of spondylolysis with intralaminar screws offers a low
      profile, reliable treatment with good functional outcome and a low complication
      rate in active patients. LEVEL OF EVIDENCE: 4.

PMID- 24108300
TI  - How to deal with cerebrospinal fluid leak during pedicle screw fixation in spinal
      deformities surgery with intraoperative neuromonitoring change.
AB  - STUDY DESIGN: A retrospective study. OBJECTIVE: To analyze the cerebrospinal
      fluid (CSF) leak during the thoracic pedicle screw fixation in spinal
      deformities, the relative intraoperative neuromonitoring changes and the strategy
      for management. SUMMARY OF BACKGROUND DATA: CSF leak may occur during the
      preparation of trajectory of thoracic pedicle screws in scoliosis surgery. The
      strategy for management of such situation is controversial. There is limited
      literature about the CSF leak and concomitant neuromonitoring change. METHODS: A
      total of 695 patients with spinal deformity subjected to correction by posterior
      instrumentation using thoracic pedicle screw fixation from 2008 January to 2010
      December and followed up for more than 2 years were retrospectively analyzed for
      CSF leak during pedicle screw placement and the concomitant neuromonitoring
      changes. The cases with CSF leak and with complete information about
      neuromonitoring were reviewed. RESULTS: A total of 7284 thoracic pedicle screws
      were inserted in the thoracic level (10.4 screws/patient). All the procedures
      were performed under the intraoperative neuromonitoring. There were 8 cases of
      CSF leak with the rate of 0.11% during the screw trajectory preparation. Seven of
      the screws located at the concave side. Five cases presented with concomitant
      positive intraoperative neuromonitoring changes. The holes were sealed for 3 of
      them, and patients presented with reversible monitoring changes and intact
      neurological function. Negligence of the CSF leak and screw insertion caused the
      deterioration of neuromonitoring even neurological deficit that needed revision
      surgery. Three cases presented without intraoperative monitoring changes and woke
      up without neurological deficit. CONCLUSION: The factors impacting the safety of
      screw placement for CSF leak included screw position, segment of vertebra, and
      concomitant neuromonitoring changes. Commonly, it was not necessary to repair the
      dural tear and sealing the pedicle hole with bone wax for the case with
      reversible neuromonitoring changes was all that needed. A lateral entry point to
      the initial one could be used and to continue the screw placement when
      neuromonitoring demonstrate reversible positive changes. LEVEL OF EVIDENCE: 4.

PMID- 24108301
TI  - Extremely wide and asymmetric anterior decompression causes postoperative C5
      palsy: an analysis of 32 patients with postoperative C5 palsy after anterior
      cervical decompression and fusion.
AB  - STUDY DESIGN: Single-center retrospective study. OBJECTIVE: We examined whether
      extremely wide and asymmetric anterior decompression causes postoperative C5
      palsy. SUMMARY OF BACKGROUND DATA: Postoperative C5 palsy is a complication of
      cervical decompression surgery. We hypothesized that C5 palsy may be caused by
      nerve root impairment through extremely wide and asymmetric dural expansion due
      to unilateral predominant wide anterior decompression with concomitant C4-C5
      foraminal stenosis. METHODS: The study included 32 patients with postoperative C5
      palsy from a cohort of 459 patients who underwent anterior cervical decompression
      and fusion at the C4-C5 disc level for cervical myelopathy. The 64 upper
      extremities were divided into 2 groups according to palsy side (n = 35) or
      nonpalsy side (n = 29). Also, to correlate radiological findings, 66 consecutive
      patients who underwent anterior cervical decompression and fusion without
      postoperative C5 palsy were selected as control. RESULTS: In patients with C5
      palsy, the unilateral decompression width on the palsy side was significantly
      larger than that on the nonpalsy side (8.63 vs. 6.92 mm, P = 0.0003). In
      addition, the decompression width was significantly larger (15.69 vs. 14.38 mm, P
      = 0.02), the diameter of the C4-C5 foramen was significantly smaller (2.73 vs.
      3.24 mm, P = 0.0008), the anterior spinal cord shift was significantly smaller
      (0.14 vs. 0.73 mm, P< 0.0001), and significant decompression asymmetry (0.74 vs.
      0.89, P = 0.0003) was present in the patients with C5 palsy compared with
      controls. CONCLUSION: Extremely wide and asymmetric decompression concomitant
      with pre-existing C4-C5 foraminal stenosis may cause postoperative C5 palsy. Our
      findings should be valuable for surgeons considering anterior cervical
      decompression and fusion that includes the C4-C5 level. Surgeons should consider
      restriction of the decompression width to less than 15 mm and avoiding asymmetric
      decompression to reduce the incidence of C5 palsy.

PMID- 24108302
TI  - Generalized disturbance of DNA methylation in the uterine decidua in the CBA/J x
      DBA/2 mouse model of pregnancy failure.
AB  - Nonchromosomal pregnancy failure is a common but poorly understood phenomenon.
      Because recent data have suggested that epigenetic abnormalities such as abnormal
      placental DNA methylation may play a role in human pregnancy failure, we
      undertook experiments to test whether decidual and/or placental DNA methylation
      abnormalities are present in a mouse model of pregnancy failure. A large number
      of studies have shown that crosses between CBA/J female mice and DBA/2 males
      result in pregnancies with a high rate of failure/resorption, whereas other
      crosses with CBA/J females produce normal pregnancies. Although the CBA/J * DBA/2
      mouse has frequently been used as a model for miscarriage, a detailed explanation
      for the pregnancy failure phenotype is lacking. We performed timed matings
      between CBA/J female and DBA/2 male mice as well as between DBA/2 female and
      CBA/J male mice. Decidual caps were isolated at Embryonic Day (E) 9.5 from both
      crosses, and a microarray-based method was used to comparatively assess genomic
      methylation at approximately 16,000 loci on mouse chromosome 7. In comparison
      with decidual caps from DBA/2 * CBA/J pregnancies, CBA/J * DBA/2 decidual caps
      were characterized by widely and apparently randomly disturbed methylation. In
      another set of analogous experiments, genomic methylation of placental DNA from
      E8.5 pregnancies was assessed using the same microarray-based method. This
      analysis revealed that in contrast to the decidua, placental DNA methylation from
      CBA/J * DBA/2 pregnancies was indistinguishable from that of normal controls. We
      conclude that abnormal DNA methylation in the uterine decidua likely plays a role
      in the CBA/J * DBA/2 model of pregnancy failure. To our knowledge, these
      experiments are the first to demonstrate that epigenetic abnormalities of the
      decidua are associated with pregnancy failure, and they set the stage for future
      efforts to understand the role of DNA methylation at the maternal-fetal
      interface.

PMID- 24108303
TI  - Conservation and expression of PIWI-interacting RNA pathway genes in male and
      female adult gonad of amniotes.
AB  - The PIWI-interacting RNA (piRNA) pathway is essential for germline development
      and transposable element repression. Key elements of this pathway are members of
      the piRNA-binding PIWI/Argonaute protein family and associated factors (e.g.,
      VASA, MAELSTROM, and TUDOR domain proteins). PIWI-interacting RNAs have been
      identified in mouse testis and oocytes, but information about the expression of
      the different piRNA pathway genes, in particular in the mammalian ovary, remains
      incomplete. We investigated the evolution and expression of piRNA pathway genes
      in gonads of amniote species (chicken, platypus, and mouse). Database searches
      confirm a high level of conservation and revealed lineage-specific gain and loss
      of Piwi genes in vertebrates. Expression analysis in mammals shows that orthologs
      of Piwi-like (Piwil) genes, Mael (Maelstrom), Mvh (mouse vasa homolog), and Tdrd1
      (Tudor domain-containing protein 1) are expressed in platypus adult testis. In
      contrast to mouse, Piwil4 is expressed in platypus and human adult testis. We
      found evidence for Mael and Piwil2 expression in mouse Sertoli cells.
      Importantly, we show mRNA expression of Piwil2, Piwil4, and Mael in oocytes and
      supporting cells of human, mouse, and platypus ovary. We found no Piwil1
      expression in mouse and chicken ovary. The conservation of gene expression in
      somatic parts of the gonad and germ cells of species that diverged over 800
      million yr ago indicates an important role in adult male and female gonad. 

PMID- 24108304
TI  - Dynamics of imprinted DNA methylation and gene transcription for imprinting
      establishment in mouse oocytes in relation to culture duration variability.
AB  - Several studies have linked assisted reproductive technologies to aberrant
      imprinting. We previously showed that 12-day in vitro follicle culture supports
      normal imprinting establishment in mouse oocytes. The aim of the present study
      was to assess whether shortened in vitro follicle growth (8 days of culture
      compared with 12 days, as a model for human in vitro maturation) or preovulatory
      intrafollicular oocyte "aging" in culture (14 days of culture) leads to
      imprinting mutations in oocytes. Limiting-dilution bisulphite sequencing showed
      that shortened in vitro follicle growth (8 days) does not induce oocyte
      epimutations at the imprinted Snrpn and Mest genes. In contrast, extension of
      oocyte residence in large unluteinized follicles in vitro was associated with a
      low level (1 of 54 alleles) of epimutations for Mest but not for Snrpn. The
      latter condition may occur during controlled ovarian stimulation where the oocyte
      growth phase may be extended for several days. Furthermore, we studied the
      dynamics during follicle culture of transcript levels for genes previously shown
      to be essential for imprinting establishment in oocytes, including Dnmt3a,
      Dnmt3L, and Zfp57. Oocyte total mRNA levels during in vitro follicle culture
      showed the timely shutdown in transcription at the antral follicle stage, and
      total mRNA levels were comparable to those of in vivo grown equine chorionic
      gonadotropin-stimulated oocytes. 

PMID- 24108305
TI  - Waveform generation is controlled by phosphorylation and swimming direction is
      controlled by Ca2+ in sperm from the mosquito Culex quinquefasciatus.
AB  - Most animal sperm are quiescent in the male reproductive tract and become
      activated after mixing with accessory secretions from the male and/or female
      reproductive tract. Sperm from the mosquito Culex quinquefasciatus initiate
      flagellar motility after mixing with male accessory gland components, and the
      sperm flagellum displays three distinct motility patterns over time: a low
      amplitude, a long wavelength form (Wave A), a double waveform consisting of two
      superimposed waveforms over the length of the flagellum (Wave B), and finally, a
      single helical waveform that propels the sperm at high velocity (Wave C). This
      flagellar behavior is replicated by treating quiescent sperm with trypsin. When
      exposed to either broad spectrum or tyrosine kinase inhibitors, sperm activated
      by accessory gland secretions exhibited motility through Wave B but were unable
      to progress to Wave C. The MEK1/2 inhibitor UO126 and the ERK1/2 inhibitor
      FR180204 each blocked the transition from Wave B to Wave C, indicating a role for
      MAPK activity in the control of waveform and, accordingly, progressive movement.
      Furthermore, a MAPK substrate antibody stained the flagellum of activated sperm.
      In the absence of extracellular Ca(2+), a small fraction of sperm swam backwards,
      whereas most could not be activated by either accessory glands or trypsin and
      were immotile. However, the phosphatase inhibitor okadaic acid in the absence of
      extracellular Ca(2+) induced all sperm to swim backwards with a flagellar
      waveform similar to Wave A. These results indicate that flagellar waveform
      generation and direction of motility are controlled by protein phosphorylation
      and Ca(2+) levels, respectively. 

PMID- 24108306
TI  - Anion receptor chemistry: highlights from 2011 and 2012.
AB  - This review covers advances in anion complexation in the years 2011 and 2012. The
      review covers both organic and inorganic systems and also highlights the
      applications to which anion receptors can be applied such as self-assembly and
      molecular architecture, sensing, catalysis and anion transport. 

PMID- 24108307
TI  - Sumatriptan/naproxen sodium for the acute treatment of probable migraine without
      aura: a randomized study.
AB  - OBJECTIVE: Probable migraine is a common, disabling migraine subtype fulfilling
      all but one of the diagnostic criteria for migraine. This study was conducted to
      evaluate the efficacy and tolerability of sumatriptan/naproxen sodium for the
      acute treatment of probable migraine without aura. METHODS: Patients treated a
      headache of probable migraine without aura when pain was moderate or severe with
      sumatriptan/naproxen sodium ( N  = 222 intent-to-treat (ITT)) or placebo ( N  =
      221 ITT/complete case analysis (a) ) in this randomized, double-blind, parallel
      group study. RESULTS: Sumatriptan/naproxen sodium was more effective than placebo
      with respect to the co-primary efficacy endpoints two-hour pain-free response
      (29% sumatriptan/naproxen sodium vs 11% placebo, P  < 0.001) and two- to 24-hour
      sustained pain-free response (24% sumatriptan/naproxen sodium vs 9% placebo, P  <
      0.001). Sumatriptan/naproxen sodium was significantly more effective than placebo
      with respect to the secondary efficacy endpoints of pain-free response four hours
      postdose ( P  < 0.001), pain-free response maintained one to two hours postdose (
      P  = 0.034) and two to four hours postdose ( P  < 0.001), headache relief four
      hours postdose ( P  < 0.001), headache relief maintained two to four hours
      postdose ( P  = 0.015), sustained headache relief two through 24 hours postdose (
      P  = 0.002), and rescue medication use ( P  < 0.001); but not productivity
      scores. The most common adverse events were dizziness (4% sumatriptan/naproxen
      sodium,<1% placebo), dry mouth (2% sumatriptan/naproxen sodium, <1% placebo), and
      nausea (2% sumatriptan/naproxen sodium, <1% placebo). CONCLUSION:
      Sumatriptan/naproxen sodium is effective in the acute treatment of probable
      migraine as demonstrated by higher rates of freedom from pain and restoration of
      function.

PMID- 24108308
TI  - Comparative efficacy of triptans for the abortive treatment of migraine: a
      multiple treatment comparison meta-analysis.
AB  - BACKGROUND: Migraine is the most common neurological condition in developed
      countries. The abortive treatment of migraine attacks is important both for
      quality of life and costs associated with illness. Triptans, serotonin 5-HT1B/1D
      receptor agonists, effectively relieve the pain, disability, and associated
      symptoms of migraine while improving health-related quality of life. Although a
      number of direct head-to-head triptan comparisons have been made, data for all
      possible permutations are not available, and unlikely to ever be so, although in
      clinical practice such information would be useful. OBJECTIVE: We aimed to
      determine the relative efficacy of all available triptans to abort migraine
      headache among patients with previous adequate response to migraine treatments.
      METHODS: We included only double-blinded randomized clinical trials comparing
      triptans to either placebo or another triptan. Our primary outcomes were pain
      free response at two hours and 24-hour sustained pain-free response, and our
      secondary outcomes were headache response at two hours and 24-hour sustained
      headache response. We used Bayesian multiple treatment comparison meta-analyses
      of seven triptans used in adult patients to abort migraine attacks. We applied a
      random-effects analysis with meta-regression adjusting for dose. Results are
      reported as odds ratios with 95% credible intervals. RESULTS: We included data
      from 74 randomized clinical trials. All triptans were significantly superior to
      placebo for all outcomes, with the exception of naratriptan for 24-hour sustained
      pain-free response. Eletriptan consistently yielded the highest treatment effect
      estimates. For the two-hour endpoints, eletriptan was statistically significantly
      superior to sumatriptan, almotriptan, naratriptan, and frovatriptan for at least
      one of the two outcomes. Rizatriptan yielded the second highest treatment effects
      followed by zolmitriptan. For the 24-hour endpoints, eletriptan was statistically
      significantly superior to sumatriptan, rizatriptan, almotriptan, and naratriptan
      for at least one of the two outcomes. Frovatriptan data were not available at
      that endpoint. Further, the probability that eletriptan is the most likely of all
      triptans to produce a favorable outcome was 68% for pain-free response at two
      hours, and 54% for 24-hour sustained pain-free response. CONCLUSION: Triptans
      appear to offer differing treatment effects. In the populations studied
      eletriptan was most likely to produce pain-free responses that were sustained.

PMID- 24108309
TI  - Electrochemical surface-enhanced Raman spectroscopy (E-SERS) of novel
      biodegradable ionic liquids.
AB  - Electrochemical SERS (E-SERS) was used for the first time to study the
      interfacial behavior of a class of pyridinium-based biodegradable ionic liquids
      at a silver nanoparticle (AgNP) electrode surface. An isomeric series of ionic
      liquids (IL) based on 3-butoxycarbonyl-1-methylpyridinium
      bis(trifluoromethanesulfonyl)imide were prepared, which have demonstrable
      biodegradability. It was found that all four of the isomeric ionic liquids
      studied exhibited excellent electrochemical stability as binary mixtures combined
      with methanol, with the absence of any specific redox processes occurring over
      nearly 3.0 V of applied potential. Normal Raman measurements of the neat isobutyl
      IL showed a signal rich in vibrational features, with strong contributions from
      both the anion and the bulky organic cation. E-SERS of the neat isobutyl IL was
      shown to exhibit excellent potential stability, with no potential-induced
      orientational change at the metal surface. When the ionic liquids were prepared
      as methanolic binary mixtures, dissociation of the IL ions was observed, and only
      the organic cation was shown to adsorb at the Ag/solution interface. The nature
      of the substituent on the ester group of the IL series was observed to have a
      significant effect on the orientation of the cation on the metal surface, based
      on the application of the metal surface selection rules combined with
      computational data. Notably, the isobutyl and sec-butyl isomers were observed to
      have an orientation wherein the pyridinium ring was oriented perpendicular to the
      surface, while the tert-butyl and n-butyl isomers were observed to have an
      orientation wherein the pyridinium ring was lying flat on the metal surface. 

PMID- 24108310
TI  - Adverse effects of psychosocial work factors on blood pressure: systematic review
      of studies on demand-control-support and effort-reward imbalance models.
AB  - OBJECTIVES: A growing body of research has investigated the adverse effects of
      psychosocial work factors on blood pressure (BP) elevation. There is now a clear
      need for an up-to-date, critical synthesis of reliable findings on this topic.
      This systematic review aimed to evaluate the adverse effects of psychosocial work
      factors of both the demand-control-support (DCS) and effort-reward imbalance
      (ERI) models on BP among men and women, according to the methodological quality
      of the studies. METHODS: To be eligible, studies had to: (i) evaluate at least
      one psychosocial work factor, (ii) evaluate BP or hypertension, (iii) comprise
      >=100 workers, (iv) be written in English or French, and (v) be published in a
      peer-reviewed journal. RESULT: A total of 74 studies were included. Of these, 64
      examined the DCS model, and 12 looked at the ERI model, with 2 studies
      considering both models. Approximately half the studies observed a significant
      adverse effect of psychosocial work factors on BP. A more consistent effect was
      observed, however, among men than women. For job strain, a more consistent effect
      was also observed in studies of higher methodological quality, ie, studies using
      a prospective design and ambulatory BP measures. CONCLUSIONS: A more consistent
      adverse effect of psychosocial work factors was observed among men than women and
      in studies of higher methodological quality. These findings contribute to the
      current effort of primary prevention of cardiovascular disease by documenting the
      psychosocial etiology of elevated BP, a major cardiovascular risk factor.

PMID- 24108311
TI  - Triazole biotin: a tight-binding biotinidase-resistant conjugate.
AB  - The natural amide bond found in all biotinylated proteins has been replaced with
      a triazole through CuAAC reaction of an alkynyl biotin derivative. The resultant
      triazole-linked adducts are shown to be highly resistant to the ubiquitous
      hydrolytic enzyme biotinidase and to bind avidin with dissociation constants in
      the low pM range. Application of this strategy to the production of a series of
      biotinidase-resistant biotin-Gd-DOTA contrast agents is demonstrated. 

PMID- 24108312
TI  - "Adiponcosis": a new term to name the obesity and cancer link.

PMID- 24108313
TI  - The IGSF1 deficiency syndrome: characteristics of male and female patients.
AB  - CONTEXT: Ig superfamily member 1 (IGSF1) deficiency was recently discovered as a
      novel X-linked cause of central hypothyroidism (CeH) and macro-orchidism.
      However, clinical and biochemical data regarding growth, puberty, and metabolic
      outcome, as well as features of female carriers, are scarce. OBJECTIVE: Our
      objective was to investigate clinical and biochemical characteristics associated
      with IGSF1 deficiency in both sexes. METHODS: All patients (n = 42, 24 males)
      from 10 families examined in the university clinics of Leiden, Amsterdam,
      Cambridge, and Milan were included in this case series. Detailed clinical data
      were collected with an identical protocol, and biochemical measurements were
      performed in a central laboratory. RESULTS: Male patients (age 0-87 years, 17
      index cases and 7 from family studies) showed CeH (100%), hypoprolactinemia (n =
      16, 67%), and transient partial GH deficiency (n = 3, 13%). Pubertal testosterone
      production was delayed, as were the growth spurt and pubic hair development.
      However, testicular growth started at a normal age and attained macro-orchid size
      in all evaluable adults. Body mass index, percent fat, and waist circumference
      tended to be elevated. The metabolic syndrome was present in 4 of 5 patients over
      55 years of age. Heterozygous female carriers (age 32-80 years) showed CeH in 6
      of 18 cases (33%), hypoprolactinemia in 2 (11%), and GH deficiency in none. As in
      men, body mass index, percent fat, and waist circumference were relatively high,
      and the metabolic syndrome was present in 3 cases. CONCLUSION: In male patients,
      the X-linked IGSF1 deficiency syndrome is characterized by CeH,
      hypoprolactinemia, delayed puberty, macro-orchidism, and increased body weight. A
      subset of female carriers also exhibits CeH.

PMID- 24108314
TI  - The clinical course of treated hyperparathyroidism among patients receiving
      hemodialysis and the effect of cinacalcet: the EVOLVE trial.
AB  - CONTEXT: The clinical course of secondary hyperparathyroidism (sHPT) in patients
      on hemodialysis is not well described, and the effect of the calcimimetic
      cinacalcet on disease progression is uncertain. OBJECTIVE: Our objective was to
      describe 1) the clinical course of sHPT in patients treated with phosphate
      binders and/or vitamin D sterols and 2) the impact of cinacalcet on the
      occurrence of severe unremitting HPT, defined by the persistence of markedly
      elevated PTH concentrations together with hypercalcemia or parathyroidectomy
      (PTX). DESIGN AND SETTING: This was a randomized, double-blind, placebo
      controlled, global, multicenter clinical trial. PATIENTS: Of 5755 patients
      screened with moderate to severe sHPT, 3883 patients on hemodialysis were
      included in the trial. MAIN OUTCOME MEASURES: Outcomes included PTX; severe,
      unremitting HPT; and use of commercial cinacalcet (a protocol violation).
      INTERVENTION: Intervention was cinacalcet (30-180 mg daily) or placebo for up to
      64 months. RESULTS: In the 1935 patients randomized to placebo, 278 patients
      (14%) underwent PTX (median PTH 1872 pg/mL within the previous 12 weeks from
      surgery). Age, sex, geographic region, co-morbidity, calcium-containing phosphate
      binder use, and baseline serum calcium, phosphorus, and PTH concentrations were
      associated with PTX. Commercial cinacalcet was started in 443 (23%) patients
      (median PTH 1108 pg/mL before treatment began). Severe unremitting HPT developed
      in 470 patients (24%). In a multivariable Cox model, the relative hazard
      (comparing patients randomized to cinacalcet versus placebo) of severe
      unremitting HPT was 0.31 (95% confidence interval = 0.26-0.37). The relative
      hazard differed little when adjusted by baseline clinical characteristics.
      CONCLUSIONS: Severe unremitting HPT develops frequently in patients on
      hemodialysis despite conventional therapy, and cinacalcet substantially reduces
      its occurrence.

PMID- 24108315
TI  - Disuse impairs the muscle protein synthetic response to protein ingestion in
      healthy men.
AB  - BACKGROUND: Disuse leads to rapid skeletal muscle atrophy, which brings about
      numerous negative health consequences. Muscle disuse atrophy is, at least in
      part, attributed to a decline in basal (postabsorptive) muscle protein synthesis
      rates. However, it remains to be determined whether muscle disuse also impairs
      the muscle protein synthetic response to dietary protein ingestion. PURPOSE: We
      assessed muscle protein synthesis rates after protein ingestion before and after
      a period of disuse in humans. METHODS: Twelve healthy young (24 +/- 1 year) men
      underwent a 14-day period of one-legged knee immobilization by way of a full leg
      cast. Before and after the immobilization period, quadriceps cross-sectional
      area, muscle strength, skeletal muscle protein synthesis rates, and associated im
      (intramuscular) molecular signaling were assessed. Continuous infusions of l
      [ring-2H5]phenylalanine were applied to assess mixed-muscle protein fractional
      synthetic rates after the ingestion of 20 g dietary protein. RESULTS:
      Immobilization led to an 8.4% +/- 2.8% (P < .001) and 22.9% +/- 2.6% (P < .001)
      decrease in quadriceps muscle cross-sectional area and strength, respectively.
      Immobilization resulted in a 31% +/- 12% reduction in postprandial muscle protein
      synthesis rates (from 0.046% +/- 0.004% to 0.032% +/- 0.006% per hour; P < .05).
      These findings were observed without any discernible changes in the skeletal
      muscle phosphorylation status of mammalian target of rapamycin or p70 ribosomal
      protein S6 kinase. CONCLUSIONS: A short period of muscle disuse impairs the
      muscle protein synthetic response to dietary protein intake in vivo in healthy
      young men. Thus, anabolic resistance to protein ingestion contributes
      significantly to the loss of muscle mass that is observed during disuse.

PMID- 24108316
TI  - A randomized study on the effect of vitamin D3 supplementation on skeletal muscle
      morphology and vitamin D receptor concentration in older women.
AB  - CONTEXT: Studies examining whether vitamin D supplementation increases muscle
      mass or muscle-specific vitamin D receptor (VDR) concentration are lacking.
      OBJECTIVE: Our objective was to determine whether vitamin D3 4000 IU/d alters
      muscle fiber cross-sectional area (FCSA) and intramyonuclear VDR concentration
      over 4 months. DESIGN AND SETTING: This was a randomized, double-blind, placebo
      controlled study in a single center. PARTICIPANTS: Participants were 21 mobility
      limited women (aged >= 65 years) with serum 25-hydroxyvitamin D (25OHD) levels of
      22.5 to 60 nmol/L. MAIN OUTCOME MEASURES: Baseline and 4-month FCSA and
      intramyonuclear VDR were measured from vastus lateralis muscle cross-sections
      probed for muscle fiber type (I/IIa/IIx) and VDR using immunofluorescence.
      RESULTS: At baseline, mean (+/-SD) age was 78 +/- 5 years; body mass index was 27
      +/- 5 kg/m2, 25OHD was 46.3 +/- 9.5 nmol/L, and a short physical performance
      battery score was 7.95 +/- 1.57 out of 12. At 4 months, 25OHD level was 52.5 +/-
      17.1 (placebo) vs 80.0 +/- 11.5 nmol/L (vitamin D [VD]; P < .01), and change in
      25OHD level was strongly associated with percent change in intramyonuclear VDR
      concentration-independent of group (r = 0.87, P < .001). By treatment group,
      percent change in intramyonuclear VDR concentration was 7.8% +/- 18.2% (placebo)
      vs 29.7% +/- 11.7% (VD; P = .03) with a more pronounced group difference in type
      II vs I fibers. Percent change in total (type I/II) FCSA was -7.4% +/- 18.9%
      (placebo) vs 10.6% +/- 20.0% (VD; P = .048). CONCLUSION: Vitamin D3
      supplementation increased intramyonuclear VDR concentration by 30% and increased
      muscle fiber size by 10% in older, mobility-limited, vitamin D-insufficient
      women. Further work is needed to determine whether the observed effect of vitamin
      D on fiber size is mediated by the VDR and to identify which signaling pathways
      are involved.

PMID- 24108317
TI  - Relationship between asking an older adult about falls and surgical outcomes.
AB  - IMPORTANCE: More than one-third of all US inpatient operations are performed on
      patients aged 65 years and older. Existing preoperative risk assessment
      strategies are not adequate to meet the needs of the aging population.
      OBJECTIVES: To evaluate the relationship of a history of falls (a geriatric
      syndrome) to postoperative outcomes in older adults undergoing major elective
      operations. DESIGN, SETTING, AND PARTICIPANTS: This prospective, cohort study was
      conducted at a referral medical center. Persons aged 65 years and older
      undergoing elective colorectal and cardiac operations were enrolled. The
      predictor variable was having fallen in the 6 months prior to the operation. MAIN
      OUTCOMES AND MEASURES: Postoperative outcomes measured included 30-day
      complications, the need for discharge institutionalization, and 30-day
      readmission. RESULTS: There were 235 subjects with a mean (SD) age of 74 (6)
      years. Preoperative falls occurred in 33%. One or more postoperative
      complications occurred more frequently in the group with prior falls compared
      with the nonfallers following both colorectal (59% vs 25%; P = .004) and cardiac
      (39% vs 15%; P = .002) operations. These findings were independent of advancing
      chronologic age. The need for discharge to an institutional care facility
      occurred more frequently in the group that had fallen in comparison with the
      nonfallers in both the colorectal (52% vs 6%; P < .001) and cardiac (62% vs 32%;
      P = .001) groups. Similarly, 30-day readmission was higher in the group with
      prior falls following both colorectal (P = .04) and cardiac (P = .02) operations.
      CONCLUSIONS AND RELEVANCE: A history of 1 or more falls in the 6 months prior to
      an operation forecasts increased postoperative complications, the need for
      discharge institutionalization, and 30-day readmission across surgical
      specialties. Using a history of prior falls in preoperative risk assessment for
      an older adult represents a shift from current preoperative assessment
      strategies.

PMID- 24108318
TI  - Live pigs produced from genome edited zygotes.
AB  - Transcription activator-like effector nuclease (TALEN) and zinc finger nuclease
      (ZFN) genome editing technology enables site directed engineering of the genome.
      Here we demonstrate for the first time that both TALEN and ZFN injected directly
      into pig zygotes can produce live genome edited pigs. Monoallelic as well as
      heterozygous and homozygous biallelic events were identified, significantly
      broadening the use of genome editor technology in livestock by enabling gene
      knockout in zygotes from any chosen mating. 

PMID- 24108319
TI  - A systematic review of model-based economic evaluations of diagnostic and
      therapeutic strategies for lower extremity artery disease.
AB  - Lower extremity artery disease (LEAD) is a sign of wide spread atherosclerosis
      also affecting coronary, cerebral and renal arteries and is associated with
      increased risk of cardiovascular events. Many economic evaluations have been
      published for LEAD due to its clinical, social and economic importance. The aim
      of this systematic review was to assess modelling methods used in published
      economic evaluations in the field of LEAD. Our review appraised and compared the
      general characteristics, model structure and methodological quality of published
      models. Electronic databases MEDLINE and EMBASE were searched until February 2013
      via OVID interface. Cochrane database of systematic reviews, Health Technology
      Assessment database hosted by National Institute for Health research and National
      Health Services Economic Evaluation Database (NHSEED) were also searched. The
      methodological quality of the included studies was assessed by using the Philips'
      checklist. Sixteen model-based economic evaluations were identified and included.
      Eleven models compared therapeutic health technologies; three models compared
      diagnostic tests and two models compared a combination of diagnostic and
      therapeutic options for LEAD. Results of this systematic review revealed an
      acceptable to low methodological quality of the included studies. Methodological
      diversity and insufficient information posed a challenge for valid comparison of
      the included studies. In conclusion, there is a need for transparent,
      methodologically comparable and scientifically credible model-based economic
      evaluations in the field of LEAD. Future modelling studies should include
      clinically and economically important cardiovascular outcomes to reflect the
      wider impact of LEAD on individual patients and on the society. 

PMID- 24108320
TI  - Circuit reactivation dynamically regulates synaptic plasticity in neocortex.
AB  - Circuit reactivations involve a stereotyped sequence of neuronal firing and have
      been behaviourally linked to memory consolidation. Here we use multiphoton
      imaging and patch-clamp recording, and observe sparse and stereotyped circuit
      reactivations that correspond to UP states within active neurons. To evaluate the
      effect of the circuit on synaptic plasticity, we trigger a single spike-timing
      dependent plasticity (STDP) pairing once per circuit reactivation. The pairings
      reliably fall within a particular epoch of the circuit sequence and result in
      long-term potentiation. During reactivation, the amplitude of plasticity
      significantly correlates with the preceding 20-25 ms of membrane depolarization
      rather than the depolarization at the time of pairing. This circuit-dependent
      plasticity provides a natural constraint on synaptic potentiation, regulating the
      inherent instability of STDP in an assembly phase-sequence model. Subthreshold
      voltage during endogenous circuit reactivations provides a critical informative
      context for plasticity and facilitates the stable consolidation of a
      spatiotemporal sequence. 

PMID- 24108321
TI  - Ostomy-related complications after emergent abdominal surgery: a 2-year follow-up
      study.
AB  - PURPOSE: The aim of this study was to prospectively evaluate ostomy-related
      complications and describe ostomy configuration in patients undergoing acute
      abdominal surgery. SUBJECTS AND SETTING: The study sample comprised 144 patients
      with a median age of 67 years (IOR: 53.5-78 years) who underwent an intestinal
      ostomy as part of an acute abdominal surgical procedure. The research setting was
      the surgical and gynecological clinics at the Sahlgrenska University Hospital in
      Gothenburg, Sweden. METHODS: Ostomy configuration, diameter, height, and the
      presence of stomal and peristomal complications were assessed by a WOC nurse 1 to
      2 times while in hospital, once at the ostomy outpatient clinic 2 weeks after
      discharge, and at 3, 6, 12, and 24 months following ostomy creation. RESULTS: The
      types of ostomies evaluated were end colostomy (58%), end ileostomy (18%), loop
      ileostomy (17%), and loop colostomy (7%). Most stomal or peristomal complications
      occurred within 1 year after surgery (31 of 57; 54.4%). Necrosis, separation, and
      stenosis were most common in patients with an end colostomy. Peristomal skin
      complications occurred in 45% of subjects during the first 6 months after
      surgery. The ostomy's diameter decreased significantly during the hospital course
      and over the first 2 weeks following hospital discharge in patients with end
      colostomy (P< .0001), end ileostomy (P< .0081), loop ileostomy (P= .008), and
      loop colostomy (ns). Patients with a low ostomy had peristomal skin problems
      ranging between 21% and 57% over this time period. The frequency of using a
      pouching system that incorporated convexity was highest in the case of loop
      ileostomy, used in 67% at 6 months. CONCLUSION: During the first 2 weeks after
      discharge, the physical configuration of the ostomy evolves and the pouching
      system must be frequently adjusted by a WOC nurse. Stomal and peristomal
      complications are prevalent during the first 2 postoperative years and especially
      during the first 6 months.

PMID- 24108322
TI  - Deciphering logopenic primary progressive aphasia: a clinical, imaging and
      biomarker investigation.
AB  - Within primary progressive aphasia the logopenic variant remains less understood
      than the two other main variants, namely semantic and non-fluent progressive
      aphasia. This may be because of the relatively small number of explored patients
      and because of the lack of investigations with a comprehensive three-level
      characterization of cognitive, brain localization and biological aspects. The aim
      of the present study was to decipher the logopenic variant through a multimodal
      approach with a large cohort of 19 patients (age 66.5 +/- 8.7 years, symptom
      duration 3.2 +/- 0.6 years) using detailed cognitive and linguistic assessments,
      magnetic resonance imaging and perfusion single-photon emission computed
      tomography as well as cerebrospinal fluid biomarkers screening for Alzheimer
      pathology. The linguistic assessment unveiled that language dysfunction is not
      limited to the typical feature of word finding and verbal working memory
      impairments but that it extends into the language system affecting to some degree
      syntactic production, phonological encoding and semantic representations.
      Perfusion tomography revealed damage of the temporal-parietal junction with a
      peak of significance in the superior temporal gyrus (Brodmann area 42), and of
      some less significant prefrontal areas (Brodmann areas 8, 9 and 46), whereas
      hippocampal cortices were unaffected. Magnetic resonance imaging, which was
      visually assessed in a larger group of 54 patients with logopenic, non-fluent,
      semantic variants as well as with posterior cortical atrophy, confirmed that the
      logopenic variant demonstrates predominant atrophy of left temporal-parietal
      junction, but that this atrophy pattern has a relatively poor sensitivity and
      specificity for clinical diagnosis. Finally, the biomarker study revealed that
      two-thirds of the logopenic patients demonstrated a profile indicative of
      Alzheimer pathology whereas one-third had a non-Alzheimer profile. Splitting the
      two groups showed that logopenic aphasia due to probable Alzheimer pathology is a
      more aggressive variant characterized by more extensive language/cognitive
      disorders affecting, in addition to lexical processes and verbal working memory,
      also phoneme sequencing, semantic processing and ideomotor praxis. Concordantly,
      logopenic aphasia due to probable Alzheimer pathology demonstrated more extensive
      brain hypoperfusion involving larger regions throughout the inferior parietal,
      the posterior-superior and the middle temporal cortex. These findings allow for
      unfolding logopenic aphasia into two subvariants differing by disease severity,
      lesion nature and lesion distribution, which has important implications for
      diagnosis, patient management and for potential future trials with anti-Alzheimer
      drugs. The present data therefore provide novel insight into the cognition and
      brain damage of logopenic patients while unveiling the existence of distinct
      diseases constituting a 'logopenic aphasia complex'. 

PMID- 24108323
TI  - Micromonospora polyrhachis sp. nov., an actinomycete isolated from edible Chinese
      black ant (Polyrhachis vicina Roger).
AB  - A novel actinomycete, designated strain NEAU-ycm2(T), was isolated from edible
      Chinese black ants (Polyrhachis vicina Roger) and characterized using a
      polyphasic approach. The organism was found to have morphological and
      chemotaxonomic characteristics typical of the genus Micromonospora. The 16S rRNA
      gene sequence of strain NEAU-ycm2(T) showed highest similarity to those of
      Micromonospora sonneratiae 274745(T) (99.12%), Micromonospora pattaloongensis TJ2
      2(T) (98.85%), Micromonospora pisi GUI 15(T) (98.76%), Polymorphospora rubra TT
      97-42(T) (98.42%) and Micromonospora eburnea LK2-10(T) (98.21%). Phylogenetic
      analysis based on the 16S rRNA gene and gyrB gene demonstrated that strain NEAU
      ycm2(T) is a member of the genus Micromonospora and supported the close
      phylogenetic relationship to M. sonneratiae 274745(T), M. pattaloongensis JCM
      12833(T) and M. pisi GUI 15(T). Furthermore, a combination of DNA-DNA
      hybridization and some physiological and biochemical properties indicated that
      the novel strain could be readily distinguished from its closest phylogenetic
      relatives. Therefore, it is proposed that NEAU-ycm2(T) represents a novel species
      of the genus of Micromonospora, for which the name Micromonospora polyrhachis sp.
      nov. is proposed. The type strain is NEAU-ycm2(T) ( = CGMCC 4.7100(T) = DSM
      45886(T)).

PMID- 24108324
TI  - Aquimarina amphilecti sp. nov., isolated from the sponge Amphilectus fucorum.
AB  - A Gram-stain-negative, rod-shaped, orange-coloured, catalase- and oxidase
      positive, non-motile bacterium, designated strain 92V(T), was isolated from the
      marine sponge Amphilectus fucorum, collected from Lough Hyne, County Cork,
      Ireland. 16S rRNA gene sequence analysis revealed that strain 92V(T) clustered
      with members of the family Flavobacteriaceae, the closest member being Aquimarina
      latercula NCIMB 1399(T), with a gene sequence similarity of 97.5%. Strain 92V(T)
      required seawater for growth with optimal growth occurring at 25  degrees C, at
      pH 6-7 and with 3% (w/v) NaCl. MK-6 was the sole respiratory quinone present and
      the major fatty acids were iso-C(17 : 0) 3-OH, iso-C(15 : 0), iso-C(17 :
      1)omega9c and iso-C(15 : 0) 3-OH. The DNA G+C content was 36.1 mol%. Combined
      phenotypic differences and phylogenetic analysis indicate that strain 92V(T)
      represents a novel species of the genus Aquimarina, for which the name Aquimarina
      amphilecti sp. nov. is proposed. The type strain is 92V(T) ( = NCIMB 14723(T) =
      DSM 25232(T)).

PMID- 24108325
TI  - Methanobacterium movilense sp. nov., a hydrogenotrophic, secondary-alcohol
      utilizing methanogen from the anoxic sediment of a subsurface lake.
AB  - A novel strain of methanogenic archaea, designated MC-20(T), was isolated from
      the anoxic sediment of a subsurface lake in Movile Cave, Mangalia, Romania. Cells
      were non-motile, Gram-stain-negative rods 3.5-4.0 um in length and 0.6-0.7 um in
      width, and occurred either singly or in short chains. Strain MC-20(T) was able to
      utilize H2/CO2, formate, 2-propanol and 2-butanol as substrate, but not acetate,
      methanol, ethanol, dimethyl sulfide, monomethylamine, dimethylamine or
      trimethylamine. Neither trypticase peptone nor yeast extract was required for
      growth. The major membrane lipids of strain MC-20(T) were archaeol
      phosphatidylethanolamine and diglycosyl archaeol, while archaeol
      phosphatidylinositol and glycosyl archaeol were present only in minor amounts.
      Optimal growth was observed at 33  degrees C, pH 7.4 and 0.08 M NaCl. Based on
      phylogenetic analysis of 16S rRNA gene sequences, strain MC-20(T) was closely
      affiliated with Methanobacterium oryzae FPi(T) (similarity 97.1%) and
      Methanobacterium lacus 17A1(T) (97.0%). The G+C content of the genomic DNA was
      33.0 mol%. Based on phenotypic and genotypic differences, strain MC-20(T) was
      assigned to a novel species of the genus Methanobacterium for which the name
      Methanobacterium movilense sp. nov. is proposed. The type strain is MC-20(T) ( =
      DSM 26032(T) = JCM 18470(T)).

PMID- 24108326
TI  - Kurthia huakuii sp. nov., isolated from biogas slurry, and emended description of
      the genus Kurthia.
AB  - A novel facultatively anaerobic bacterium, designated strain LAM0618(T), was
      isolated from biogas slurry samples collected from the large-scale anaerobic
      digester of Modern Farming Corporation in Hebei Province, China. Cells of strain
      LAM0618(T) were Gram-stain-positive, motile, non-spore-forming and short-rod
      shaped. The optimal temperature and pH for growth were 30  degrees C and 7.0,
      respectively. The strain did not require NaCl for growth but tolerated up to 70 g
      NaCl l(-1). The major fatty acids of strain LAM0618(T) were iso-C(15 : 0),
      anteiso-C(15 : 0), iso-C(14 : 0), C(16 : 0) and C(18 : 0). The predominant
      menaquinones of strain LAM0618(T) were menaquinone 7 (MK-7) and menaquinone 6 (MK
      6). The main polar lipids of strain LAM0618(T) were phosphatidylglycerol,
      diphosphatidylglycerol, phosphatidylethanolamine and six unknown glycolipids. The
      genomic DNA G+C content was 41 mol% as determined by the Tm method. Analysis of
      the 16S rRNA gene sequence revealed that strain LAM0618(T) was a member of the
      genus Kurthia, and was most closely related to 'Kurthia massiliensis' DSM 24639,
      Kurthia zopfii DSM 20580(T), Kurthia gibsonii DSM 20636(T) and Kurthia sibirica
      DSM 4747(T), with 96.9, 95.7, 95.6 and 94.9 % sequence similarity, respectively.
      Based on its phenotypic and genotypic properties, strain LAM0618(T) is suggested
      to represent a novel species of the genus Kurthia, for which the name Kurthia
      huakuii sp. nov. is proposed. The type strain is LAM0618(T) ( = ACCC 06121(T) =
      JCM 19187(T)).

PMID- 24108327
TI  - Distinct responses of soil microbial communities to elevated CO2 and O3 in a
      soybean agro-ecosystem.
AB  - The concentrations of atmospheric carbon dioxide (CO2) and tropospheric ozone
      (O3) have been rising due to human activities. However, little is known about how
      such increases influence soil microbial communities. We hypothesized that
      elevated CO2 (eCO2) and elevated O3 (eO3) would significantly affect the
      functional composition, structure and metabolic potential of soil microbial
      communities, and that various functional groups would respond to such atmospheric
      changes differentially. To test these hypotheses, we analyzed 96 soil samples
      from a soybean free-air CO2 enrichment (SoyFACE) experimental site using a
      comprehensive functional gene microarray (GeoChip 3.0). The results showed the
      overall functional composition and structure of soil microbial communities
      shifted under eCO2, eO3 or eCO2+eO3. Key functional genes involved in carbon
      fixation and degradation, nitrogen fixation, denitrification and methane
      metabolism were stimulated under eCO2, whereas those involved in N fixation,
      denitrification and N mineralization were suppressed under eO3, resulting in the
      fact that the abundance of some eO3-supressed genes was promoted to ambient, or
      eCO2-induced levels by the interaction of eCO2+eO3. Such effects appeared
      distinct for each treatment and significantly correlated with soil properties and
      soybean yield. Overall, our analysis suggests possible mechanisms of microbial
      responses to global atmospheric change factors through the stimulation of C and N
      cycling by eCO2, the inhibition of N functional processes by eO3 and the
      interaction by eCO2 and eO3. This study provides new insights into our
      understanding of microbial functional processes in response to global atmospheric
      change in soybean agro-ecosystems. 

PMID- 24108329
TI  - Loline alkaloid production by fungal endophytes of Fescue species select for
      particular epiphytic bacterial microflora.
AB  - The leaves of fescue grasses are protected from herbivores by the production of
      loline alkaloids by the mutualist fungal endophytes Neotyphodium sp. or Epichloe
      sp. Most bacteria that reside on the leaf surface of such grasses can consume
      these defensive chemicals. Loline-consuming bacteria are rare on the leaves of
      other plant species. Several bacterial species including Burkholderia ambifaria
      recovered from tall fescue could use N-formyl loline as a sole carbon and
      nitrogen source in culture and achieved population sizes that were about
      eightfold higher when inoculated onto plants harboring loline-producing fungal
      endophytes than on plants lacking such endophytes or which were colonized by
      fungal variants incapable of loline production. In contrast, mutants of B.
      ambifaria and other bacterial species incapable of loline catabolism achieved
      similarly low population sizes on tall fescue colonized by loline-producing
      Neotyphodium sp. and on plants lacking this endophytic fungus. Lolines that are
      released onto the surface of plants benefiting from a fungal mutualism thus
      appear to be a major resource that can be exploited by epiphytic bacteria,
      thereby driving the establishment of a characteristic bacterial community on such
      plants. 

PMID- 24108328
TI  - Genetic and functional properties of uncultivated MCG archaea assessed by
      metagenome and gene expression analyses.
AB  - The Miscellaneous Crenarchaeota group (MCG) Archaea is one of the predominant
      archaeal groups in anoxic environments and may have significant roles in the
      global biogeochemical cycles. However, no isolate of MCG has been cultivated or
      characterized to date. In this study, we investigated the genetic organization,
      ecophysiological properties and evolutionary relationships of MCG archaea with
      other archaeal members using metagenome information and the result of gene
      expression experiments. A comparison of the gene organizations and similarities
      around the 16S rRNA genes from all available MCG fosmid and cosmid clones
      revealed no significant synteny among genomic fragments, demonstrating that there
      are large genetic variations within members of the MCG. Phylogenetic analyses of
      large-subunit+small-subunit rRNA, concatenated ribosomal protein genes and
      topoisomerases IB gene (TopoIB) all demonstrate that MCG constituted a sister
      lineage to the newly proposed archaeal phylum Aigarchaeota and Thaumarchaeota.
      Genes involved in protocatechuate degradation and chemotaxis were found in a MCG
      fosmid 75G8 genome fragment, suggesting that this MCG member may have a role in
      the degradation of aromatic compounds. Moreover, the expression of a putative 4
      carboxymuconolactone decarboxylase was observed when the sediment was
      supplemented with protocatechuate, further supporting the hypothesis that this
      MCG member degrades aromatic compounds. 

PMID- 24108331
TI  - Role of polyethylene glycol in childhood constipation.
AB  - Constipation is a common and chronic problem in children worldwide. Long-term use
      of laxatives is necessary for successful treatment of chronic constipation.
      Commonly used laxatives in children include milk of magnesia, lactulose, mineral
      oil, and polyethylene glycol (PEG). Recent studies report the efficacy and safety
      of PEG for the long-term treatment of constipation in children. Because of its
      excellent patient acceptance, PEG is being used widely in children for
      constipation. In this commentary, we review the recently published pediatric
      literature on the efficacy, safety, and patient acceptance of PEG. We also assess
      the role of PEG in childhood constipation by comparing it with other laxatives in
      terms of efficacy, safety, patient acceptance, and cost. 

PMID- 24108332
TI  - [The importance of subjectivity].

PMID- 24108330
TI  - Gene-targeted metagenomic analysis of glucan-branching enzyme gene profiles among
      human and animal fecal microbiota.
AB  - Glycoside hydrolases (GHs), the enzymes that breakdown complex carbohydrates, are
      a highly diversified class of key enzymes associated with the gut microbiota and
      its metabolic functions. To learn more about the diversity of GHs and their
      potential role in a variety of gut microbiomes, we used a combination of 16S,
      metagenomic and targeted amplicon sequencing data to study one of these enzyme
      families in detail. Specifically, we employed a functional gene-targeted
      metagenomic approach to the 1-4-alpha-glucan-branching enzyme (gBE) gene in the
      gut microbiomes of four host species (human, chicken, cow and pig). The
      characteristics of operational taxonomic units (OTUs) and operational glucan
      branching units (OGBUs) were distinctive in each of hosts. Human and pig were
      most similar in OTUs profiles while maintaining distinct OGBU profiles.
      Interestingly, the phylogenetic profiles identified from 16S and gBE gene
      sequences differed, suggesting the presence of different gBE genes in the same
      OTU across different vertebrate hosts. Our data suggest that gene-targeted
      metagenomic analysis is useful for an in-depth understanding of the diversity of
      a particular gene of interest. Specific carbohydrate metabolic genes appear to be
      carried by distinct OTUs in different individual hosts and among different
      vertebrate species' microbiomes, the characteristics of which differ according to
      host genetic background and/or diet. 

PMID- 24108333
TI  - [Effect of posteroventral pallidotomy on event-related P300 in Parkinson's
      disease].
AB  - BACKGROUND: Ablative procedures are still frequent for the surgical treatment of
      Parkinson's disease (PD). Although the P300 component has been used to assess
      cognitive changes induced by levodopa and deep brain stimulation (DBS), the
      effects caused by unilateral pallidotomy remain unknown. MATERIAL AND METHODS:
      P300 amplitude and latency in 10 PD patients who underwent unilateral pallidotomy
      with and without levodopa treatment were compared with 10 healthy controls.
      Measurements in patients were performed 6 months before and after surgery while
      only once in controls, throughout the 6-month lapse between the comparative
      measurements performed in patients. RESULTS: Statistical differences in P300
      amplitude and latency were found between the control and PD groups (p < 0.001).
      On the other hand, there were no differences between the groups with the use of
      the levodopa treatment or surgery. DISCUSSION: Lack of statistically significant
      results after six months of pallidotomy or treatment with levodopa suggests an
      absence of cognitive impairment. Our results obtained with P300 in which safety
      of surgical treatment has been assessed in PD are consistent with those of other
      procedures, such as DBS.

PMID- 24108334
TI  - [Rituximab in pediatric patients with systemic lupus erythematosus].
AB  - Systemic lupus erythematosus (SLE) is an autoimmune disease that is more severe
      in pediatric population than in adults. Biological therapy with anti-CD20
      (rituximab) in children with SLE was begun to use only a few years ago, in
      patients that do not respond to conventional therapy. The aim of this study is to
      determine the clinical response in pediatric patients with SLE that received
      treatment with rituximab in a third level hospital. RESULTS: Eight pediatric
      patients with SLE treated with rituximab were included. Female gender
      predominated with six (75%). The age at diagnosis of SLE was a mean of 11.3 +/-
      1.03 years. The mean time between the onset of symptoms and diagnosis was 4.12 +/
      1.01 months, and the application of rituximab was 20.7 +/- 6.2 months after
      diagnosis. The most common diagnostic criteria were: malar erythema, hematologic
      disease, arthritis and kidney disease. Positive ANA title was found in 62.5% of
      the patients. The clinical activity index MEX-SLEDAI before rituximab was 11.63
      +/- 6.8 points. Four patients (50%) died, they had activity index before
      rituximab of 23 +/- 1.7 and the survivors of 12.2 +/- 3.2 (p = 0.002). After
      treatment with rituximab the patients that died had 17.6 +/- 8.5 points and the
      survivors 8 +/- 2.1 (p = 0.038). In laboratory findings, only C3 and C4 had a
      significant change after treatment (p = 0.048 and 0.032). CONCLUSIONS: Rituximab
      reduces lupus activity index and increases complement levels in children with LES
      that don't respond to conventional therapy.

PMID- 24108335
TI  - [Profile characterization of Parkinson's disease in Mexico: ReMePARK study].
AB  - INTRODUCTION: The Mexican Registry of Parkinson's disease (ReMePARK) is nested
      within a multicentric cohort aimed to describe motor, non-motor, and genetic
      determinants of Parkinson's disease in Mexican patients. MATERIAL AND METHODS: To
      date, clinical and demographic data from 1,083 subjects has been obtained. Here
      we present the demographic and clinical data of the current sample along with its
      comparison with international reports. RESULTS: A total of 607 male and 476
      female subjects with Parkinson's disease were included. The mean age of the
      patients was 64.7 +/- 12.9 years. The time from onset of symptoms to diagnosis
      was 2.4 +/- 2.6 years. About 34% of subjects had only elementary education. Of
      the subjects, 54.4% were under treatment with dopamine agonists. CONCLUSION:
      Subjects with Parkinson's disease incorporated into ReMePARK are comparable with
      other international registries, with the exception of the years of formal
      education, time to diagnosis, and the use of dopamine agonists. The
      characterization of the Mexican population with Parkinson's disease will improve
      diagnosis and therapeutic management as well as define research efforts in this
      area. Finally, registry future directions are presented.

PMID- 24108336
TI  - [General aspects of pulmonary innervation].
AB  - Practically all organs of the respiratory system are under the control of the
      autonomic nervous system. Double vegetative innervation, sympathetic and
      parasympathetic, contributes to the regulation of airway smooth muscle tone, and
      modulates secretion from the submucosal glands. Nevertheless, more than 20 years
      ago, the classical view of excitatory cholinergic and inhibitory adrenergic
      innervation changed considerably when the existence was proved of the non
      adrenergic non-cholinergic system (NANC), which is able to produce both effects.
      Several purines and peptides have been postulated as neurotransmitters of this
      system, and some of them coexist with the acetylcholine or norepinephrine; for
      example, vasoactive intestinal peptide (VIP) on cholinergic nerves and
      neuropeptide Y in the adrenergic nerves. The aim of this paper is to describe the
      anatomo-physiological aspects of the airways' autonomic innervation and the
      possible implication of a neural mechanism that contributes in the development of
      the symptomatology in respiratory diseases. 

PMID- 24108337
TI  - [Usefulness, validity, and reliability of ultrasound in the diagnosis of
      osteoarthritis: a critical review of the literature].
AB  - Ultrasound is outstripping other diagnostic imaging techniques in the evaluation
      of osteoarthritis (OA). Due to its sub-millimetric resolution, ultrasound has the
      ability to detect minimal morphostructural abnormalities, even from preclinical
      or asymptomatic disease stages located in the main joint structures predominantly
      affected by OA: articular cartilage, synovial membrane, and subchondral bone. As
      of today, ultrasound has proven to be a useful tool for the detection of
      abnormalities occurring within soft tissues, including synovial hypertrophy,
      fluid accumulation, and synovial cysts, as well as bony abnormalities, such as
      osteophyte formation. Additionally, power Doppler signal correlated with
      histologic evidence of synovial membrane vascularization. In order to describe
      the ultrasonographic findings of OA, its utility, reliability, and validity as a
      diagnostic and monitoring tool, a critical review of the literature of hand, hip,
      and knee OA is provided.

PMID- 24108338
TI  - [Tumor necrosis factor alfa in cardiovascular diseases: molecular biology and
      genetics].
AB  - Cardiovascular diseases are a major public health problem globally. In 1997,
      cardiovascular disease caused 41% of deaths in the United States. It has been
      reported that about 60 million people in the United States have some form of
      cardiovascular disease. These entities are chronic conditions initiated by a
      dysregulation of the immune response. One gene and its protein product -tumor
      necrosis factor a (TNF-alpha)- a powerful pleiotropic cytokine with multiple
      cellular functions, plays a role in the inflammation, initiation, development,
      susceptibility, severity, and response to treatment, etc. of coronary artery
      disease (CAD). The focus of the present review is to summarize recent evidence
      showing the biological role of TNF-alpha in the initiation and progression of
      endothelial dysfunction and complications of atherosclerosis, and as a genetic
      variation of TNF-alpha confer susceptibility, severity, and treatment response in
      CAD: ST-segment elevation myocardial infarction and non-ST segment elevation
      myocardial infarction, unstable angina, and coronary restenosis. 

PMID- 24108339
TI  - [Immune responses and immunopathogenesis in infections with dengue virus].
AB  - We still have an incomplete understanding of both immunoprotection and
      immunopathogenesis mechanisms in dengue. Proper balance among the components of
      the immune response plays an important role in protection as well as in
      pathogenesis because these impact clinical outcomes and severity of dengue cases.
      In this article, we review the elements of the immune response that participate
      in DENV infections, and we contrast the levels of immune effectors in both
      classic dengue fever and the severe dengue fever cases. We also emphasize the
      components frequently related to the immunopathogenesis in dengue. It is clear
      that several effectors are increased or dysregulated in the severe cases.
      Finally, the global mechanism that contributes to the subversion of the immune
      system in dengue hemorrhagic fever or dengue shock syndrome still requires
      complete elucidation. 

PMID- 24108340
TI  - [Clinical and immunological characteristics in pediatric patients with
      coccidioidomycosis in northeastern Mexico].
AB  - BACKGROUND: Coccidioidomycosis is a systemic fungal disease caused by
      Coccidioides spp. Patients with phagocytic, cellular, or humoral
      immunodeficiencies exhibit immunodeficiencies that confer increased
      susceptibility to fungal infections. In Mexico there is an underreporting of this
      disease and no studies currently describe the immune status of these patients in
      an endemic area. OBJECTIVE: To describe the clinical and immunological
      characteristics of pediatric patients with coccidioidomycosis. MATERIALS AND
      METHODS: Pediatric patients with diagnosis of coccidioidomycosis from two
      tertiary level hospitals of northeastern Mexico were included, from the period
      2008-2012; immune status was assessed by clinical history, immunoglobulins
      levels, levels of lymphocytes T, B, and NK (natural killer), and the nitroblue
      tetrazolium test. RESULTS: Thirty patients were included, 18 male (60%). The age
      at diagnosis was five years (median, range 0.25-13). Twelve were from Coahuila
      (40%). Residual pulmonary coccidioidomycosis was the clinical type presentation
      found in 16 patients (53%). A primary humoral immunodeficiency was found in three
      patients (10%) and a secondary immunodeficiency in another three (10%). Case
      fatality rate was 16%. CONCLUSIONS: . The disease predominated in male patients.
      In 33% of patients, levels of IgG were elevated, probably due to stimulation by
      chronic fungal infection. In 20% of patients, immunodeficiency was documented.
      There was a high mortality rate.

PMID- 24108341
TI  - [Trigeminal-cavernous fistula. Report of a case and review of the literature].
AB  - Persistent primitive trigeminal artery is a rare anatomical variant resulting
      from the absence of obliteration of the embryonic trigeminal artery. The shunt
      between the persistent primitive trigeminal artery and the cavernous sinus is
      called trigeminal-cavernous fistula. We report the case of a woman with a
      trigeminal-cavernous fistula secondary to head trauma who was treated by
      transarterial embolization. 

PMID- 24108342
TI  - [Eagle's Syndrome].
AB  - Eagle's Syndrome is an entity that is rarely clinically and anatomopathologically
      identified, and is defined as the elongation of the styloid process and/or the
      calcification of the styloid ligament. It produces intense pain in the
      craniocervical region and limitation of cervical movements. It can be mistaken
      for temporomandibular joint dysfunction. The diagnosis of this entity can be done
      by physical examination with palpation of the styloid process in the tonsillar
      fossa, and radiological studies help confirm the diagnosis. 

PMID- 24108343
TI  - [Human resources for health in the context of the reform of the health system in
      Mexico: professional training and labor market].
AB  - The role that human resources for health should play in future stages of the
      Mexican Health System reform is discussed. The following dimensions are
      considered to guide the discussion: the orientation of training, the institutions
      responsible for training, the mechanisms to link graduates to health institutions
      and the ways health workers should respond to the current managerial
      modifications. Changes should be based on a pre-defined strategic planning
      exercise based on institutional agreements which allow defining common objectives
      as well as clear procedures to attain those objectives. 

PMID- 24108344
TI  - [Equity, public health and genomics: the legal, social and biotechnology
      challenge in Mexico].
AB  - Mexico has entered an era where health research is enriched by the study of
      genetic variants that determinate how the different human populations are
      differentially susceptible to diseases. The objective is to design new strategies
      in health care and services based on medical genomics. However, to ensure
      universal access to these products, we should rethink the legal aspects that
      facilitate the design of health policies, based on the principle of equity.
      Intrinsic factors of the Mexican health system as inequity, poverty and low
      investment in health research, are challenges that add to the development of
      appropriate distribution strategies for the use of new genomic products for
      health. This article discusses these challenges and establish the basis to design
      policies and appropriate use of these new genomic-based health care services. 

PMID- 24108345
TI  - [The National Academy of Medicine of Mexico (1836-1912)].
AB  - The article presents a summary of the development of the National Academy of
      Medicine of Mexico since its beginnings in 1836, when the first Academy was
      created, until 1912 when the organization became an official institution and an
      advisory authority for the Federal Government. The different stages that the
      Academy has gone through show the dynamism of the corporation and the activity
      and energy of its members. As a whole, they advanced medicine in the country at
      the same time as the Academy fought for the recognition, consolidation, and
      support of its research. 

PMID- 24108346
TI  - [Mortality trends and years of potential life lost from prostate cancer in the 32
      states and 7 sociecononomic regions of Mexico, 2000-2010].
AB  - OBJECTIVE: To determine trends of mortality from prostate cancer (PC) and years
      of potential life lost (YPLL) by federative entity and by socioeconomic region in
      the period 2000-2010. METHODS: Records of mortality associated with PC 2000-2010
      were obtained from the National Information System of the Secretariat of Health.
      This information is generated by the National Institute of Statistics and
      Geography through death certificates issued throughout the country. International
      Classification of Diseases, 10th revision, codes corresponding to the basic cause
      of death from PC were identified. Rates of mortality nationwide, by state, and by
      socioeconomic region were calculated. Rates of YPLL were calculated by federative
      entity and by socioeconomic region. The seven socioeconomic regions were
      elaborated by the National Institute of Statistics and Geography and include the
      31 states and Mexico City according to indicators that are related to well-being
      such as education, occupation, health, housing, and employment. RESULTS: Raw
      mortality rates per 100,000 inhabitants who died from PC increased from 7.8 to
      9.8 between 2000-2010. The states and socioeconomic regions with the higher rates
      of mortality from PC were Sinaloa, Sonora, Baja California Sur, Nayarit, Colima
      and regions 6 and 3. The state and socioeconomic regions with higher rate of APVP
      from PC were Aguascalientes, Nuevo Leon, Campeche, Baja California Sur, Durango
      and regions 6, 5, 3, 1 and 2. CONCLUSIONS: Raw mortality rates per 100,000
      inhabitants who died from PC increased from 7.8 to 9.8 between 2000-2010. The
      states and socioeconomic region with the higher mortality rates were Sinaloa,
      Sonora, Baja California Sur, Nayarit, Colima and regions 6 and 3. Mexico.

PMID- 24108348
TI  - Electronic excited states of a strongly correlated organic radical 1,3,5-trithia
      2,4,6-triazapentalenyl (TTTA) adsorbed on a Si(001) surface.
AB  - Electronic excited states of a strongly correlated organic radical, 1,3,5-trithia
      2,4,6-triazapentalenyl (TTTA), adsorbed on a Si(001) surface were investigated by
      means of two-photon photoemission spectroscopy (2PPE) to elucidate the functional
      organic thin-film formation on a typical semiconductor substrate. The spectra
      were interpreted with the aid of density functional theoretical calculations. The
      unpaired electron of TTTA forms a covalent bond with the dangling bond of the Si
      dimer initially, and there are resonant states of TTTA to Si near the surface.
      The molecules adsorbed at room temperature form dimers having diamagnetic
      properties at thicknesses of a few monolayers, while the paramagnetic phase
      appears at multilayer thickness. From the change in the work function, the
      orientation of the adsorbed TTTA molecules was determined to change depending on
      the thickness of the adsorbed layer. 

PMID- 24108347
TI  - [Update on the epidemiology of mycetoma in Mexico. A review of 3933 cases].
AB  - Mycetoma is one of the most frequent chronic subcutaneous infections in many
      tropical and subtropical regions. OBJECTIVE: To update the epidemiological data
      of mycetoma cases in Mexico. METHOD: A survey in the main mycological diagnosis
      centers in this country was performed. Each mycologist was requested for number
      of diagnosed mycetoma cases, age, sex, occupation, geographic origin, type of
      mycetoma, and etiological agents. RESULTS: Until 2012, we have registered 3,933
      cases in the last 54 years. Sex distribution corresponds to 75.6% for men and
      24.4% for women. In 75.72% is present in adults between 16-50 years old. The
      predominant work group of patients is farmers (58.41%) followed by housewives
      (21.79%). Most of patients come from Jalisco, Morelos, Nuevo Leon, Guerrero,
      Veracruz and Michoacan states. The most affected body areas are limbs (60.29%)
      and trunk (19.76%). Actinomycetoma has a frequency of 96.52%, and the commonest
      etiological agent is Nocardia brasiliensis (65.58%). Eumycetoma (3.48%) is mainly
      caused by Madurella grisea (28.47%) and M. mycetomatis (26.28%). CONCLUSIONS:
      Mycetoma is an under-diagnosed pathology representing a health problem in rural
      regions and must be attended with more interest by the health institutions.

PMID- 24108349
TI  - Thermo- and mechanical-grinding-triggered color and luminescence switches of the
      diimine-platinum(II) complex with 4-bromo-2,2'-bipyridine.
AB  - The square-planar diimine-platinum(II) complex, Pt(4-Brbpy)(C=CC6H5)2 (1) (4
      Brbpy = 4-bromo-2,2'-bipyridine), was prepared and characterized. Solid-state 1
      exhibits reversible thermo- and mechanical-grinding-triggered color and
      luminescence changes. When crystalline 1.2(CH2Cl2) or 1.2(CHCl3) are heated or
      ground, the original bright yellow-green emission centered at 525 (549, sh) nm
      changed to 637 and 690 nm, corresponding to thermo- and mechanochromic response
      shifts of approximately 88-112 nm and 141-165 nm, respectively. Meanwhile the
      crystalline state changes into an amorphous phase in both processes. Once the
      amorphous sample absorbs organic vapors, it can be reverted to the original
      crystalline state, along with red luminescence turning back to yellow-green
      emission. The reversibility of thermo- and mechanical-grinding-triggered chromic
      luminescence properties has been dynamically monitored by emission spectra and X
      ray diffraction patterns. The dramatic thermo- and mechanical-grinding-triggered
      emission red shifts are most likely due to the conversion of the (3)MLCT/(3)LLCT
      emission state into the (3)MMLCT triplet state.

PMID- 24108350
TI  - Design and biological evaluation of synthetic retinoids: probing length vs.
      stability vs. activity.
AB  - All trans-retinoic acid (ATRA) is widely used to direct the differentiation of
      cultured stem cells. When exposed to the pluripotent human embryonal carcinoma
      (EC) stem cell line, TERA2.cl.SP12, ATRA induces ectoderm differentiation and the
      formation of neuronal cell types. We report in this study that novel polyene
      chain length analogues of ATRA require a specific chain length to elicit a
      biological responses of the EC cells TERA2.cl.SP12, with synthetic retinoid AH61
      being particularly active, and indeed more so than ATRA. The impacts of both the
      synthetic retinoid AH61 and natural ATRA on the TERA2.cl.SP12 cells were directly
      compared using both RT-PCR and Fourier Transform Infrared Micro-Spectroscopy (FT
      IRMS) coupled with multivariate analysis. Analytical results produced from this
      study also confirmed that the synthetic retinoid AH61 had biological activity
      comparable or greater than that of ATRA. In addition to this, AH61 has the added
      advantage of greater compound stability than ATRA, therefore, avoiding issues of
      oxidation or decomposition during use with embryonic stem cells. 

PMID- 24108351
TI  - Tandem triad systems based on FRET for two-photon induced release of glutamate.
AB  - Tandem systems allowing enhanced two-photon (2P) absorption in a wavelength range
      permitting coupling of the primary excitation by energy transfer to an
      intramolecular cage known to have fragmentation properties suited to photolysis
      in neuroscience is demonstrated to lead to a 10-fold improvement in the 2P
      photolysis cross-section at experimentally compatible wavelengths. 

PMID- 24108352
TI  - Spectral multidimensional scaling.
AB  - An important tool in information analysis is dimensionality reduction. There are
      various approaches for large data simplification by scaling its dimensions down
      that play a significant role in recognition and classification tasks. The
      efficiency of dimension reduction tools is measured in terms of memory and
      computational complexity, which are usually a function of the number of the given
      data points. Sparse local operators that involve substantially less than
      quadratic complexity at one end, and faithful multiscale models with quadratic
      cost at the other end, make the design of dimension reduction procedure a
      delicate balance between modeling accuracy and efficiency. Here, we combine the
      benefits of both and propose a low-dimensional multiscale modeling of the data,
      at a modest computational cost. The idea is to project the classical
      multidimensional scaling problem into the data spectral domain extracted from its
      Laplace-Beltrami operator. There, embedding into a small dimensional Euclidean
      space is accomplished while optimizing for a small number of coefficients. We
      provide a theoretical support and demonstrate that working in the natural
      eigenspace of the data, one could reduce the process complexity while maintaining
      the model fidelity. As examples, we efficiently canonize nonrigid shapes by
      embedding their intrinsic metric into , a method often used for matching and
      classifying almost isometric articulated objects. Finally, we demonstrate the
      method by exposing the style in which handwritten digits appear in a large
      collection of images. We also visualize clustering of digits by treating images
      as feature points that we map to a plane. 

PMID- 24108353
TI  - Correction of mutations within the cystic fibrosis transmembrane conductance
      regulator by site-directed RNA editing.
AB  - Adenosine deaminases that act on RNA are a conserved family of enzymes that
      catalyze a natural process of site-directed mutagenesis. Biochemically, they
      convert adenosine to inosine, a nucleotide that is read as guanosine during
      translation; thus when editing occurs in mRNAs, codons can be recoded and the
      changes can alter protein function. By removing the endogenous targeting domains
      from human adenosine deaminase that acts on RNA 2 and replacing them with an
      antisense RNA oligonucleotide, we have engineered a recombinant enzyme that can
      be directed to edit anywhere along the RNA registry. Here we demonstrate that
      this enzyme can efficiently and selectively edit a single adenosine. As proof of
      principle in vitro, we correct a premature termination codon in mRNAs encoding
      the cystic fibrosis transmembrane conductance regulator anion channel. In Xenopus
      oocytes, we show that a genetically encoded version of our editase can correct
      cystic fibrosis transmembrane conductance regulator mRNA, restore full-length
      protein, and reestablish functional chloride currents across the plasma membrane.
      Finally, in a human cell line, we show that a genetically encoded version of our
      editase and guide RNA can correct a nonfunctional version of enhanced green
      fluorescent protein, which contains a premature termination codon. This
      technology should spearhead powerful approaches to correcting a wide variety of
      genetic mutations and fine-tuning protein function through targeted nucleotide
      deamination. 

PMID- 24108354
TI  - Insect nicotinic receptor interactions in vivo with neonicotinoid,
      organophosphorus, and methylcarbamate insecticides and a synergist.
AB  - The nicotinic acetylcholine (ACh) receptor (nAChR) is the principal insecticide
      target. Nearly half of the insecticides by number and world market value are
      neonicotinoids acting as nAChR agonists or organophosphorus (OP) and
      methylcarbamate (MC) acetylcholinesterase (AChE) inhibitors. There was no
      previous evidence for in vivo interactions of the nAChR agonists and AChE
      inhibitors. The nitromethyleneimidazole (NMI) analog of imidacloprid, a highly
      potent neonicotinoid, was used here as a radioligand, uniquely allowing for
      direct measurements of house fly (Musca domestica) head nAChR in vivo
      interactions with various nicotinic agents. Nine neonicotinoids inhibited house
      fly brain nAChR [(3)H]NMI binding in vivo, corresponding to their in vitro
      potency and the poisoning signs or toxicity they produced in intrathoracically
      treated house flies. Interestingly, nine topically applied OP or MC insecticides
      or analogs also gave similar results relative to in vivo nAChR binding inhibition
      and toxicity, but now also correlating with in vivo brain AChE inhibition,
      indicating that ACh is the ultimate OP- or MC-induced nAChR active agent. These
      findings on [(3)H]NMI binding in house fly brain membranes validate the nAChR in
      vivo target for the neonicotinoids, OPs and MCs. As an exception, the remarkably
      potent OP neonicotinoid synergist, O-propyl O-(2-propynyl) phenylphosphonate,
      inhibited nAChR in vivo without the corresponding AChE inhibition, possibly via a
      reactive ketene metabolite reacting with a critical nucleophile in the cytochrome
      P450 active site and the nAChR NMI binding site. 

PMID- 24108355
TI  - Ligand-specific conformational change of the G-protein-coupled receptor ALX/FPR2
      determines proresolving functional responses.
AB  - Formyl-peptide receptor type 2 (FPR2), also called ALX (the lipoxin A4 receptor),
      conveys the proresolving properties of lipoxin A4 and annexin A1 (AnxA1) and the
      proinflammatory signals elicited by serum amyloid protein A and cathelicidins,
      among others. We tested here the hypothesis that ALX might exist as homo- or
      heterodimer with FPR1 or FPR3 (the two other family members) and operate in a
      ligand-biased fashion. Coimmunoprecipitation and bioluminescence resonance energy
      transfer assays with transfected HEK293 cells revealed constitutive dimerization
      of the receptors; significantly, AnxA1, but not serum amyloid protein A, could
      activate ALX homodimers. A p38/MAPK-activated protein kinase/heat shock protein
      27 signaling signature was unveiled after AnxA1 application, leading to
      generation of IL-10, as measured in vitro (in primary monocytes) and in vivo
      (after i.p. injection in the mouse). The latter response was absent in mice
      lacking the ALX ortholog. Using a similar approach, ALX/FPR1 heterodimerization
      evoked using the panagonist peptide Ac2-26, identified a JNK-mediated
      proapoptotic path that was confirmed in primary neutrophils. These findings
      provide a molecular mechanism that accounts for the dual nature of ALX and
      indicate that agonist binding and dimerization state contribute to the
      conformational landscape of FPRs. 

PMID- 24108356
TI  - Lanthanide near infrared imaging in living cells with Yb3+ nano metal organic
      frameworks.
AB  - We have created unique near-infrared (NIR)-emitting nanoscale metal-organic
      frameworks (nano-MOFs) incorporating a high density of Yb(3+) lanthanide cations
      and sensitizers derived from phenylene. We establish here that these nano-MOFs
      can be incorporated into living cells for NIR imaging. Specifically, we introduce
      bulk and nano-Yb-phenylenevinylenedicarboxylate-3 (nano-Yb-PVDC-3), a unique MOF
      based on a PVDC sensitizer-ligand and Yb(3+) NIR-emitting lanthanide cations.
      This material has been structurally characterized, its stability in various media
      has been assessed, and its luminescent properties have been studied. We
      demonstrate that it is stable in certain specific biological media, does not
      photobleach, and has an IC50 of 100 MUg/mL, which is sufficient to allow live
      cell imaging. Confocal microscopy and inductively coupled plasma measurements
      reveal that nano-Yb-PVDC-3 can be internalized by cells with a cytoplasmic
      localization. Despite its relatively low quantum yield, nano-Yb-PVDC-3 emits a
      sufficient number of photons per unit volume to serve as a NIR-emitting reporter
      for imaging living HeLa and NIH 3T3 cells. NIR microscopy allows for highly
      efficient discrimination between the nano-MOF emission signal and the cellular
      autofluorescence arising from biological material. This work represents a
      demonstration of the possibility of using NIR lanthanide emission for biological
      imaging applications in living cells with single-photon excitation. 

PMID- 24108357
TI  - SUMOylation regulates the SNF1 protein kinase.
AB  - The AMP-activated protein kinase (AMPK) is a major stress sensor of mammalian
      cells. AMPK's homolog in the yeast Saccharomyces cerevisiae, the SNF1 protein
      kinase, is a central regulator of carbon metabolism that inhibits the Snf3/Rgt2
      Rgt1 glucose sensing pathway and activates genes involved in respiration. We
      present evidence that glucose induces modification of the Snf1 catalytic subunt
      of SNF1 with the small ubiquitin-like modifier protein SUMO, catalyzed by the
      SUMO (E3) ligase Mms21. Our results suggest that SUMOylation of Snf1 inhibits its
      function in two ways: by interaction of SUMO attached to lysine 549 with a SUMO
      interacting sequence motif located near the active site of Snf1, and by targeting
      Snf1 for destruction via the Slx5-Slx8 (SUMO-directed) ubiquitin ligase. These
      findings reveal another way SNF1 function is regulated in response to carbon
      source. 

PMID- 24108359
TI  - Stereoselective preparation of lipidated carboxymethyl-proline/pipecolic acid
      derivatives via coupling of engineered crotonases with an alkylmalonyl-CoA
      synthetase.
AB  - The trisubstituted enolate- and C-C bond-forming capacities of engineered
      carboxymethylproline synthases CMPSs are coupled with the malonyl-CoA synthetase
      MatB to enable stereoselective preparation of 5- and 6-membered N-heterocycles
      functionalised with alkyl-substituted carboxymethyl side chains, starting from
      achiral alkyl-substituted malonic acids and L-amino acid semialdehydes. The
      results illustrate the biocatalytic utility of crotonases in tandem enzyme
      catalysed reactions for stereoselective synthesis.

PMID- 24108358
TI  - Structural and functional characterization of two alpha-synuclein strains.
AB  - alpha-Synuclein aggregation is implicated in a variety of diseases including
      Parkinson's disease, dementia with Lewy bodies, pure autonomic failure and
      multiple system atrophy. The association of protein aggregates made of a single
      protein with a variety of clinical phenotypes has been explained for prion
      diseases by the existence of different strains that propagate through the
      infection pathway. Here we structurally and functionally characterize two
      polymorphs of alpha-synuclein. We present evidence that the two forms indeed
      fulfil the molecular criteria to be identified as two strains of alpha-synuclein.
      Specifically, we show that the two strains have different structures, levels of
      toxicity, and in vitro and in vivo seeding and propagation properties. Such
      strain differences may account for differences in disease progression in
      different individuals/cell types and/or types of synucleinopathies.

PMID- 24108360
TI  - Mandatory contrast-enhanced venography to detect deep-vein thrombosis (DVT) in
      studies of DVT prophylaxis: upsides and downsides.
AB  - The introduction of venography into patient care was a major advance because it
      was the first accurate method for the diagnosis of DVT. Compression ultrasound
      has since become the preferred test for patients with suspected DVT because,
      unlike venography, it is simple, non-invasive and widely available. Venography
      has facilitated the development and approval of new anticoagulants and remains
      widely used as an efficacy outcome in trials of venous thromboembolism
      prevention. Most thrombi detected by screening venography are, however, small and
      unimportant for patients. In order to calculate the trade-off between an
      asymptomatic thrombus and a bleed we require an estimate of the number of
      asymptomatic thrombi that must be prevented to avoid a patient-important
      thrombus. A credible estimate of this ratio is not available. Therefore when used
      as a measure of efficacy in trials of thromboprophylaxis, venography has
      limitations for comparing the relative effects of alternative antithrombotic
      agents on outcomes important to patients.

PMID- 24108362
TI  - NaH mediated isomerisation-allylation reaction of 1,3-substituted propenols.
AB  - A base mediated isomerisation-allylation protocol of 1,3-disubstituted propenols
      has been established. The use of diaryl and aryl-silyl substrates is reported
      alongside the use of substituted allyl bromides. Mechanistic experiments have
      also been conducted to elucidate the reaction pathway. 

PMID- 24108361
TI  - Hydrogen production by tuning the photonic band gap with the electronic band gap
      of TiO2.
AB  - Tuning the photonic band gap (PBG) to the electronic band gap (EBG) of Au/TiO2
      catalysts resulted in considerable enhancement of the photocatalytic water
      splitting to hydrogen under direct sunlight. Au/TiO2 (PBG-357 nm) photocatalyst
      exhibited superior photocatalytic performance under both UV and sunlight compared
      to the Au/TiO2 (PBG-585 nm) photocatalyst and both are higher than Au/TiO2
      without the 3 dimensionally ordered macro-porous structure materials. The very
      high photocatalytic activity is attributed to suppression of a fraction of
      electron-hole recombination route due to the co-incidence of the PBG with the EBG
      of TiO2 These materials that maintain their activity with very small amount of
      sacrificial agents (down to 0.5 vol.% of ethanol) are poised to find direct
      applications because of their high activity, low cost of the process, simplicity
      and stability.

PMID- 24108363
TI  - Making progress with magnetic resonance spectroscopy.

PMID- 24108364
TI  - A new nasopharyngeal dynamic reference frame improves accuracy in navigated skull
      base targets.
AB  - OBJECTIVE: We questioned whether the position of the dynamic reference frame
      (DRF) influences the application accuracy in electromagnetically navigated
      cranial procedures. A carrier for an electromagnetic DRF was developed, which
      could be fixed at the posterior edge of the vomer near the center of the head.
      This nasopharyngeal DRF was compared with a standard DRF fixed to the surface of
      the forehead. METHODS: Image coordinates and real-world coordinates were co
      registered and the total target error (TTE) was measured in the frontal and the
      lateral skull base of formalin fixed human head. At each anatomical site, 10
      targets served for TTE determinations and 5 different fiducial combinations were
      used for registration. RESULTS: With the nasopharyngeal DRF, lower TTE values
      (2.8 +/- 1.4 mm; mean +/- SD) were observed when compared with the forehead DRF
      (3.7 +/- 2.8 mm; P = .004). TTEs of both anatomical sites investigated were
      significantly lower when using the nasopharyngeal DRF (frontal skull base 3.4 vs
      2.1 mm, P = .005 and lateral skull base 3.9 vs 3.5 mm, P = .013) than with the
      standard forehead mounted one. CONCLUSION: Positioning the DRF in the center of
      the head significantly improved the application accuracy of targets in the skull
      base with electromagnetic navigation by 25%.

PMID- 24108365
TI  - Polymorphism -2604G>A variants in TLR4 promoter are associated with different
      gene expression level in peripheral blood of atherosclerotic patients.
AB  - Toll-like receptor-4 (TLR4) is a primary receptor of the innate immune reaction
      and compelling evidence demonstrates its involvement in the pathogenesis of
      atherosclerosis and stroke. TLR4 is constitutively expressed on monocytes and
      endothelial cells; it is highly expressed in atherosclerotic plaques and in
      peripheral blood of patients after ischemic stroke. Polymorphisms in the promoter
      region that alter the transcriptional regulation of this gene may represent
      genetic risk factors involved in the predisposition to atherosclerotic disease.
      In this study we investigated the effect on TLR4 gene expression of three
      polymorphisms in the upstream regulatory region at positions -1607T>C/rs10759932,
      -2026A>G/rs1927914 and -2604G>A/rs10759931 in peripheral blood of atherosclerotic
      patients. RNA from individuals homozygous for the -2604A allele showed a lower
      expression of the gene when compared to patients carrying the counterparts GG+GA.
      Electrophoretic mobility shift assays showed differences in the electrophoretic
      mobility of the DNA-nuclear protein complexes formed by the G>A variants,
      suggesting that the two alleles differ in their binding affinity to
      transcriptional factors. 

PMID- 24108366
TI  - Comprehensive analysis of common and rare mitochondrial DNA variants in elite
      Japanese athletes: a case-control study.
AB  - The purpose of the present study was to identify mitochondrial DNA (mtDNA)
      polymorphisms and rare variants that associate with elite Japanese athletic
      status. Subjects comprised 185 elite Japanese athletes who had represented Japan
      at international competitions (that is, 100 endurance/middle-power athletes: EMA;
      85 sprint/power athletes: SPA) and 672 Japanese controls (CON). The entire mtDNA
      sequences (16 569 bp) were analyzed by direct sequencing. Nucleotide variants
      were detected at 1488 sites in the 857 entire mtDNA sequences. A total of 311
      variants were polymorphisms (minor allele frequency 1% in CON), and the
      frequencies of these polymorphisms were compared among the three groups. The EMA
      displayed excess of seven polymorphisms, including subhaplogroup D4e2- and D4g
      specific polymorphisms, compared with CON (P<0.05), whereas SPA displayed excess
      of three polymorphisms and dearth of nine polymorphisms, including haplogroup G-
      and subhaplogroup G2a-specific polymorphisms, compared with CON (P<0.05). The
      frequencies of 10 polymorphisms, including haplogroup G- and subhaplogroup G2a
      specific polymorphisms, were different between EMA and SPA (P<0.05): although
      none of these polymorphisms differed significantly between groups after
      correcting for multiple comparison (false discovery rate q-value 0.05). The
      number of rare variants in the 12S ribosomal RNA and NADH dehydrogenase subunit I
      genes were also higher in SPA than in CON (P<0.05). Analysis of the entire mtDNA
      of elite Japanese athletes revealed several haplogroup- and subhaplogroup
      specific polymorphisms to be potentially associated with elite Japanese athletic
      status.

PMID- 24108367
TI  - Nematicons and their electro-optic control: light localization and signal
      readdressing via reorientation in liquid crystals.
AB  - Liquid crystals in the nematic phase exhibit substantial reorientation when the
      molecules are driven by electric fields of any frequencies. Exploiting such a
      response at optical frequencies, self-focusing supports transverse localization
      of light and the propagation of self-confined beams and waveguides, namely
      "nematicons". Nematicons can guide other light signals and interact with
      inhomogeneities and other beams. Moreover, they can be effectively deviated by
      using the electro-optic response of the medium, leading to several strategies for
      voltage-controlled reconfiguration of light-induced guided-wave circuits and
      signal readdressing. Hereby, we outline the main features of nematicons and
      review the outstanding progress achieved in the last twelve years on beam self
      trapping and electro-optic readdressing. 

PMID- 24108368
TI  - CD8+ T cell-induced expression of tissue inhibitor of metalloproteinses-1
      exacerbated osteoarthritis.
AB  - Despites the fact that T cells are involved in the pathogenesis of osteoarthritis
      (OA) little is known about the roles of CD8+ T cells in this disease. We
      investigated the effects of CD8+ T cells and the expression of tissue inhibitor
      of metalloproteinases 1 (TIMP-1) on joint pathology. Using anterior cruciate
      ligament-transection (ACLT), OA was induced in mice. The knee joints were
      histologically assessed for manifestations of OA. The CD8+ T cells from
      splenocytes and synovium were flow-cytometrically and immunochemically evaluated,
      respectively. Local expression of TIMP-1, matrix metalloproteinase (MMP)-13, and
      VEGF were examined. Cartilage degeneration was slower in CD8+ T cell knockout
      mice than in control mice. CD8+ T cells were activated once OA was initiated and
      expanded during OA progression. More CD8+ T cells from splenocytes expressed TIMP
      1 in ACLT-group mice than in Sham-group mice. The number of TIMP-1-expressing
      CD8+ T cells in OA mice correlated with the disease severity. TIMP-1 expression
      in cartilage was co-localized with that of MMP-13 and VEGF. TIMP-1 protein was
      detected in synovium in which angiogenesis occurred. During the pathogenesis of
      OA, the expression of TIMP-1, VEGF and MMP-13 accompanying with CD8+ T cells
      activation were increased. Furthermore, inhibiting the expression of TIMP-1 in
      joints could retard the progression of OA. 

PMID- 24108369
TI  - Eleven novel polymorphic microsatellite Loci for oval squid Sepioteuthis
      lessoniana (Shiro-Ika type).
AB  - The oval squid Sepioteuthis lessoniana is one of the most economically important
      squid species in Japan; however, its population structure is poorly understood
      due to the lack of hypervariable markers. Such information is critical for
      managing sustainable fisheries, as well as for ensuring the existence of wild S.
      lessoniana stocks. Eleven candidate microsatellite loci were isolated from a
      small insert genomic DNA library. Polymorphisms in these 11 loci were screened in
      24 wild individuals. The number of alleles per locus was found to range from 5 to
      19 alleles, and the observed heterozygosity ranged from 0.292 to 0.958. No
      evidence for linkage disequilibrium was detected among all the loci. The
      genotypic proportions conformed to Hardy-Weinberg equilibrium, except at one
      locus. In conclusion, these polymorphic microsatellite loci may be used to
      develop a genetic framework to manage S. lessoniana in the future. 

PMID- 24108371
TI  - Organometallic turnstiles: acid and base locking and unlocking.
AB  - A symmetrical organometallic Pt(II) based molecular turnstile 1, composed of a
      rotor bearing two benzonitrile units as coordinating sites and a stator equipped
      with a dianionic tridentate coordinating pole, undergoes a reversible switching
      process between two open and one closed states. In the absence of an effector,
      the turnstile is in its open state defined by the free rotation of the rotor
      around the stator. In the presence of Pd(II), the latter is simultaneously
      complexed by both the rotor and the stator (1-Pd) leading to the first closed
      state owing to locking of the rotational movement. The turnstile can be unlocked
      to its second open state 1-Pd-DMAP by addition of para-dimethylaminopyridine
      (DMAP) behaving as an external competitive ligand replacing the bound
      benzonitrile in the coordination sphere of the Pd centre. Upon addition of
      PdCl2(CH3CN)2, a competitive metal complex to remove DMAP, the turnstile is
      switched back to its closed state. The same process can also be achieved upon
      addition of MsOH causing the protonation of DMAP into DMAP-H(+) and its
      decomplexation and replacement by one of the two benzonitrile groups of the
      rotor. Finally, the deprotonation of DMAP-H(+) by addition of Et3N as a base
      regenerates the second open state of the turnstile.

PMID- 24108370
TI  - N,N'-alkylated Imidazolium-derivatives act as quorum-sensing inhibitors targeting
      the Pectobacterium atrosepticum-induced symptoms on potato tubers.
AB  - Bacteria belonging to the Pectobacterium genus are the causative agents of the
      blackleg and soft-rot diseases that affect potato plants and tubers worldwide. In
      Pectobacterium, the expression of the virulence genes is controlled by quorum
      sensing (QS) and N-acylhomoserine lactones (AHLs). In this work, we screened a
      chemical library of QS-inhibitors (QSIs) and AHL-analogs to find novel QSIs
      targeting the virulence of Pectobacterium. Four N,N'-bisalkylated imidazolium
      salts were identified as QSIs; they were active at the uM range. In potato tuber
      assays, two of them were able to decrease the severity of the symptoms provoked
      by P. atrosepticum. This work extends the range of the QSIs acting on the
      Pectobacterium-induced soft-rot disease. 

PMID- 24108372
TI  - [Medical and scientific research in Peru: newfields].

PMID- 24108373
TI  - [Clinical and endoscopic features of a selected population with serrated
      colorectal adenomas in a private clinic in Lima - Peru].
AB  - OBJECTIVE: To describe the clinical and endoscopic caracteristics of a population
      that has only serrated polyps of colon (mainly sessile serrated adenomas) in a
      private clinic in Lima, Peru, from 2009-2011. MATERIALS AND METHODS:
      Retrospective study conducted at the endoscopy center of Clinic Ricardo Palma,
      Lima, Peru. Olympus colonoscope was used with high definition, including NBI
      (narrow band imaging) and electronic magnification. Patients had pathologic
      diagnosis of a?oepolyps and / or colorectal serrated adenomasa?? and excluded
      those with synchronous tubular or villous adenomas. Images were evaluated by two
      endoscopists and then by a third gastroenterologist. RESULTS: We found 201
      serrated polyps in 108 patients. Women were 60.2% and overweight predominated.
      Eighty (74.1%) had only one serrated adenoma and 23 (21.3%) with at least one
      synchronous hyperplastic polyp. The average size of sessile serrated adenomas was
      5.12 mm (A+/- 3.87 DS) and the flat type was 91 (58.7%). There were significant
      differences in the diameter of sessile serrated adenomas between the distal and
      proximal colon (4.47 mm A+/- 2.23 vs. 6.90 mm A+/- 6.25; p<0.000). The common
      features of sessile serrated adenomas were: White (31/36, 86.1%), smooth (28/36,
      77.8%) and regular margins (26/36, 72.2%). There was a relationship between
      vascular pattern according NBI and serrated polyp histology (p=0.024).
      CONCLUSION: The endoscopic features of sessile serrated adenomas can evade
      detection to white light. NBI is a useful tool to define some features of these
      lesions.

PMID- 24108374
TI  - [Impact of duodenopancreatectomy in elder patients].
AB  - The incidence of periampullary neoplasms substantially increases with age. If we
      take into account that this incidence is higher in the elder patient and that
      life expectancy is nowadays longer, questioning surgical approach in this group
      of patients turns out to be controversial. OBJECTIVE: [corrected] Asses if in the
      elder patients the duodenopancreatectomy has a higher mortality and
      complications. MATERIALS AND METHODS: A retrospective study including patients
      who underwent duodenopancreatectomy between October 2002 and June 2012 was
      undertaken to assess whether the elder ones had a higher morbidity and mortality
      after surgery. Patients were distributed in two groups according to age. The
      first group included 240 patients younger than 75 years, and the second one
      included 74 patients older than 75 years. There wasn't NO significant difference
      in morbidity between the two groups. RESULTS: General mortality for the whole
      series was 4%. The first group had a 2.9% mortality whereas in the second one
      mortality reached 4.9%, a significant difference. However, when we changed the
      reference age from 75 years to 65 or 70 years the difference was not significant
      any more. CONCLUSION: From this study we can ascertain that an age more than 75
      years significantly increases the mortality risk in duodenopancreatectomy
      patients. This age, however, doesn't proscribe surgical approach, since surgery
      is the only choice for curative treatment in patients with this type of cancer.

PMID- 24108375
TI  - [Risk factors associated to mortality by upper GI bleeding in patients from a
      public hospital. A case control study].
AB  - OBJECTIVE: Identify and establish risk factors associated with mortality
      secondary to upper gastrointestinal bleeding up to 30 days after the episode, at
      the Hospital Nacional Cayetano Heredia. MATERIAL AND METHODS: A retrospective
      analytic observational case-control study was made with a case: control
      proportion of 1:3, analyzing 180 patient from which 135 were the controls and 45
      the cases. It was determined by biological plausibility as potential risk factors
      to 14 variables, with which were performed bivariate and multivariate logistic
      analyses. RESULTS: It was found in the bivariate logistic analysis as variables
      statistically related to mortality: age (OR=1.02), hematemesis (OR=2.57), in
      hospital upper gastrointestinal bleeding (OR=4), cirrhosis (OR=2.67), malignancy
      (OR=5,37), admittance to intensive care unit/Shock-Trauma (OR=9.29), Rockall
      score greater than 4 (OR=19.75), rebleeding (OR=5.65), and number of packed red
      blood cell transfusions(OR=1.22). While in the multivariate logistic analysis,
      the only variables statistically related to mortality were: malignancy (OR=5.35),
      admittance to intensive care unit/Shock-Trauma (OR=8.29), and Rockall score
      greater than 4 (OR=8.43). CONCLUSIONS: The factors that increase the risk of
      mortality in patient with upper gastrointestinal bleeding are: Rockall score
      greater than 4, admittance to intensive care unit/Shock-Trauma, rebleeding, in
      hospital upper gastrointestinal bleeding, cirrhosis, hematemesis, malignancy, the
      number of red blood cell transfusion, and age.

PMID- 24108376
TI  - [Frequency and mortality by rebleeding in cirrhotic patients treated for bleeding
      esophagic varices in two hospitals in Lima Peru during years 2009 to 2011].
AB  - During the first 6 weeks after a variceal hemorrhage there is a 30-40% of
      probability of recurrence and those who rebleed 20- 30% die. Passed this period,
      the risk of rebleeding is of 60% and reaches a mortality of 60-70% in two years
      without treatment. OBJECTIVE: Describe the frequency of rebleeding and mortality
      due to rebleeding in cirrhotic patients treated for variceal hemorrhage at
      Endoscopic Centers of Hospital Nacional Cayetano Heredia, Lima, Peru and Hospital
      Nacional Arzobispo Loayza, Lima, Peru during the years 2009-2011. MATERIALS AND
      METHODS: The study type is a transversal, periodic and retrospective one in which
      were included 176 cirrhotic patients older than 14 years who have bleed for
      esophageal varices and that have received endoscopic therapy. The instruments
      used were a data sheet with all the information obtained from the clinical chart
      of each patient, the CHILD score to assess severity of hepatic disease,
      endoscopic informs and phone calls. RESULTS: The frequency of rebleeding before 6
      weeks was 32.20% (56 patients). Also, the frequency of rebleeding after that time
      was 22.56% (37 patients). There was a mortality rate of 5.70% (10 patients) and a
      mortality rate due to rebleeding of 13.33% (6 patients). CONCLUSIONS: Variceal
      hemorrhage is an important cause of mobimortality in peruvian people. The
      frequency of rebleeding and mortality due to rebleeding resulted slightly lower
      than in other countries.

PMID- 24108377
TI  - [Endoscopic management of the complications of pancreatitis].
AB  - Acute and chronic pancreatitis may lead to complications that prior the recent
      advancement of therapeutic endoscopy had to be treated with conventional surgery.
      The current techniques in interventional endoscopy allow us to access the
      pancreas and treat some of the complications in a minimally invasive way leading
      to less morbidity in our patients. Approximately 90% of acute pancreatitis
      episodes are edematous with early resolution of clinical symptoms and rarely
      leading to major complications. Patients with necrotizing pancreatitis are
      susceptible to local and systemic complications particularly in the setting of
      organ failure. On the other hand chronic pancreatitis is as a chronic
      inflammatory process that leads to fibrosis of the gland and in occasions to
      exocrine and/or endocrine insufficiency. The main objective of therapeutic
      endoscopy in chronic pancreatitis is to relief the obstruction and decreases the
      pressure in the pancreatic duct with the intention to alleviate abdominal pain.
      In this review we will address the indications and endoscopic techniques to treat
      the different complications of pancreatitis such as pseudo cyst drainage, walled
      off necrosis debridement, disconnected duct syndrome and different options for
      endoscopic therapy in chronic pancreatitis. 

PMID- 24108378
TI  - [Chronic liver disease associated with cystic fibrosis in the Hospital Alberto
      Sabogal Sologuren, Lima, Peru: report of a case].
AB  - Cystic fibrosis (CF) is the most frequent recessive genetic disorder in the
      caucasian population and is produced by the alteration of electrolyte and water
      transport in the epithelial cell membrane. Liver disease is a frequent
      complication towards the end of the first decade of life, being weird its onset,
      except in patients with a history of meconium ileus. The characteristic liver
      injury in CF is focal biliary cirrhosis, but fatty infiltration can also be
      found. The diagnosis is made considering the clinical, laboratory and imaging
      results having in consideration that the normal liver function tests do not rule
      out the disease. Ultrasound is the most widely used and can detect the presence
      of steatosis, stones, fibrosis, cirrhosis, portal hypertension or abnormalities
      of the biliary tree. There is an also available technique such as computed
      tomography or magnetic resonance imaging, which allows a morphological study.
      Important aspects in the treatment are nutritional management, administration of
      soluble vitamins and the use of ursodeoxycholic acid (UDCA). In cases of advanced
      cirrhosis, transplantation, isolated or combined with the lung, is an option to
      consider, with acceptable survival rates. We report the case of an 11 year old
      patient with a diagnosis of chronic liver disease associated with cystic
      fibrosis. 

PMID- 24108379
TI  - [Colonic intussusception by leiomyosarcoma].
AB  - We report the case of female patient, 34 years old, occupation Secretary.
      BACKGROUND: Polycystic ovary and chronic anemia. No family history of cancer. The
      patient reported three weeks abdominal pain, fever, bloody loose stools, nausea
      and vomiting. Abdominal pain is located in flank and right lower quadrant, is
      colicky, intensity 5 / 10, associated with abdominal distension. On physical
      examination, vital functions indicated T 38.6 A degrees  FC 98 x min, FR 18 x
      min, BP 120/80, was awake, she looked pale, in generally fair condition, lucid
      and oriented. The abdomen was distended, the increased bowel sounds, tympanic to
      percussion, with tenderness in the right abdomen (more intense in the right iliac
      fossa), palpable mass is not defined edges lower right quadrant of about 6cm.
      CLINICAL DIAGNOSIS: abdominal pain syndrome (appendicular mass, intestinal
      obstruction, intussusceptions). In examinations auxiliars highlighted in 9.1 g of
      hemoglobin with decreased corpuscular constants. Reviewed by history "rectal
      bleeding", DRE: yellow stool, no trace of blood, so that colonoscopy was
      deferred. Reassessed at 24 hours, we decide surgery with a presumptive diagnosis
      of intestinal obstruction, intussusception. In surgery, we identified a
      transverse colon tumor (with colo-colonic intussusception) and 10cm of colon was
      resected and meso tumor: TT anastomosis was performed in transverse colon. The
      lesion was a tumor of the middle region of the transverse colon, proliferative
      fibroid appearance, which almost completely obstructed the intestinal lumen,
      measuring about 7x5cm. The study of pathology with immunohistochemistry indicated
      that the tumor corresponded to leiomyosarcoma of the colon. Was discharged in
      good condition. The rarity of this type of malignancy and this type of
      presentation led us to make this report.

PMID- 24108380
TI  - [Acute portal thrombosis and gas in the liver: a report of two cases].
AB  - The presence in adults of intrahepatic portal gas is a multifactorial event in
      which systemic inflammatory and prothrombotic factors coexist, it is common in
      patients with advanced liver cirrhosis and rare in those with a healthy liver,
      however its frequency increases with the presence of inflammatory abdominal
      disorders and hypercoagulability related to systemic inflammatory response, their
      manifestations are unspecific and varies according to severity. We study two
      cases with unspecific symptoms, where imaging studies reported intrahepatic
      portal gas, one secondary to diverticular disease and the second related to liver
      abscesses, which favorably response with surgical, antibiotic and anticoagulant
      treatment. 

PMID- 24108381
TI  - [Giant retroperitoneal solitary fibrous tumor: report of a case].
AB  - Giant solitary fibrous tumor (TFSG) is a spindle cell neoplasm, uncommon, being
      pleural a common site. We report a case of chronic presentation of 4 months
      duration with a palpable mass. We found, a tumor 35 x 20 x 15 cm .In the
      literature tumors diagnosed as TFSG are very rare, the first reported in our
      country. 

PMID- 24108382
TI  - [How to approach the rise of liver enzymes in healthy people? The importance for
      the general practitioner].
AB  - In this study we make a review of the most common causes of the rise of the
      levels of aminotransferases, alkaline fosphatase and gamma glutamil
      transpeptidase en healthy people, also we offer a view of the diagnosis and
      management of these patients as simple as possible. 

PMID- 24108383
TI  - Superacid-doped polybenzimidazole-decorated carbon nanotubes: a novel high
      performance proton exchange nanocomposite membrane.
AB  - Here we demonstrate design and electrochemical characterization of novel proton
      exchange membranes based on Nafion and superacid-doped polymer coated carbon
      nanotubes (CNTs). Polybenzimidazole-decorated CNT (PBI-CNT), a high-performance
      proton exchange nanostructure, was doped using phosphotungstic acid (PWA) as a
      super proton conductor. The engineered nanohybrid structure was shown to retain
      water molecules and provide high proton conduction at low humidity and elevated
      temperatures. The developed complex nanomaterial was then incorporated into the
      Nafion matrix to fabricate nanocomposite membranes. The acid-base interactions
      between imidazole groups of PBI and sulfonate groups of Nafion facilitate proton
      conductivity, especially at elevated temperatures. The improved characteristics
      of the membranes at the nanoscale result in enhanced fuel cell power generation
      capacity (386 mW cm(-2)) at elevated temperatures and low humidity (40% R.H.),
      which was found to be considerably higher than the commercial Nafion(r)117
      membrane (73 mW cm(-2)). 

PMID- 24108384
TI  - Risk of fatal unintentional injuries in children by migration status: a
      nationwide cohort study with 46 years' follow-up.
AB  - BACKGROUND: Injuries are responsible for much child and adolescent mortality in
      the world. OBJECTIVE: To study the effect of parental birth country on the risk
      of fatal unintentional injuries. METHODS: We established a cohort by linkages
      between Swedish national registers through personal identification number. The
      main variable was country of birth of parents. Children with both parents born in
      Sweden were the reference group. The cohort was followed up from the starting
      date of the study (1 January 1961) or date of birth, whichever occurred last,
      until the exit date, which was death due to unintentional injury, first
      emigration or end of the follow-up (31 December 2007), whichever came first. We
      calculated HRs with 95% CIs adjusted for age at exit, parental education and
      calendar period of birth by Cox proportional hazards models. RESULTS: We found a
      significantly higher risk of fatal unintentional injuries among children with a
      foreign background than among native children. We found a higher risk of fatal
      transportation-related injuries and drowning among boys with a foreign background
      and a higher risk of fatal burns/fire and falls among girls with a foreign
      background than among same sex native children. We also found a higher risk of
      fatal unintentional injuries among children with a foreign background at older
      ages than among native children at the same ages. CONCLUSIONS: Injury prevention
      work against unintentional injuries among children of foreign origin is more
      complex than that among native children. We recommend designing specific studies
      to find out the factors responsible and planning preventive interventions aiming
      at this particular group of children with a foreign background.

PMID- 24108385
TI  - The level of physical exercise is associated with self-reported health status (EQ
      5D) in adults with congenital heart disease.
AB  - BACKGROUND: The prognosis in adults with congenital aortic valve disease is
      usually favourable; nevertheless, a number of medical and social factors might
      hamper long-term prognosis and quality of life. With a focus on physical exercise
      level, data from the Swedish National Registry on Congenital Heart Disease
      (SWEDCON) were analysed and variables associated with health-related quality of
      life in adults with congenital aortic valve disease were identified. METHODS: In
      this registry study, SWEDCON was searched for adult patients with isolated
      congenital aortic valve disease and valid EuroQol-5Dimensions health
      questionnaire (EQ-5D) data. RESULTS: This study identified 315 patients. The
      majority (n = 202, 64%) reported best possible health status (EQ-5D(index) = 1)
      whereas 113 (35%) reported some impairment (EQ-5D(index) < 1) with mean EQ
      5D(index) 0.73 +/- 0.17. In a multivariate logistic regression model, self
      reported physical exercise > 3 h/week was independently associated with best
      possible health status (EQ-5D(index) = 1; p = 0.013). Moreover presence of
      cardiovascular symptoms (p < 0.001), active smoking (p = 0.002), history of valve
      surgery (p = 0.017), low educational level (p = 0.022), and higher systolic blood
      pressure (p = 0.029) were independently associated with impaired health status
      (EQ-5D(index) < 1). CONCLUSIONS: Physical exercise >3 h/week was, as a single
      variable, associated with best possible health status in adults with congenital
      aortic valve disease. In contrast, a number of medical and social factors are
      associated with worse self-reported health status. Among these, symptoms,
      smoking, and educational level are potential targets for modification and
      intervention. There is a need for studies investigating the effect of increased
      level of physical exercise in patients with congenital aortic valve disease.

PMID- 24108386
TI  - Enantioselective Michael addition of 1,3-dicarbonyl compounds to a nitroalkene
      catalyzed by chiral squaramides - a key step in the synthesis of pregabalin.
AB  - Asymmetric organocatalytic 1,4-additions provide access to a large number of
      biologically relevant compounds. Chiral squaramides efficiently catalyse
      enantioselective Michael addition of 1,3-dicarbonyl compounds to aliphatic
      nitroalkenes. The resulting gamma-nitro carboxylic derivatives were obtained in
      high yields and in high enantiomeric purities. Quantum chemical calculations
      helped us to devise a transition state model, which explains the observed
      stereochemical course of the addition. The best results were obtained with
      Meldrum's acid as a donor, with which enantiomeric purity of the Michael adduct
      was 97 : 3 e.r. Using this methodology pregabalin was synthesized in three steps
      in overall 52% yield. 

PMID- 24108387
TI  - The platelet--thrombosis and beyond.

PMID- 24108388
TI  - Methylglyoxal impairs GLUT4 trafficking and leads to increased glucose uptake in
      L6 myoblasts.
AB  - Methylglyoxal (MG) is a highly reactive dicarbonyl compound derived mainly from
      glucose degradation pathways, but also from protein and fatty acid metabolism. MG
      modifies structure and function of different biomolecules and thus plays an
      important role in the pathogenesis of diabetic complications. Hyperglycemia
      associated accumulation of MG might be associated with generation of oxidative
      stress and subsequently insulin resistance. Therefore, the effects of MG on
      insulin signaling and on translocation of glucose transporter 4 (GLUT4) were
      investigated in the rat skeletal muscle cell line L6-GLUT4myc stably expressing
      myc-tagged GLUT4. Twenty four-hour MG treatment resulted in elevated GLUT4
      presentation on the surface of L6 myoblasts and in an increased uptake of glucose
      even without insulin stimulation. Exogenously added MG neither effected IRS-1
      expression nor IRS-1 phosphorylation. A decreased expression of Akt1 but not Akt2
      and concomitantly increased apoptosis were detected following MG treatment. To
      exclude that oxidative stress caused by MG treatment leads to increased GLUT4
      translocation, effects of pretreatment with 2 antioxidants were investigated. The
      antioxidant and MG scavenger NAC prevented the MG-induced GLUT4 translocation. In
      contrast, tiron, a well-known antioxidant that does not exert MG-scavenger
      function, had no impact on MG-induced GLUT4 translocation supporting the
      hypothesis of a direct effect of MG on GLUT4 trafficking. In conclusion,
      prolonged treatment with MG augments GLUT4 level on the surface of L6 myoblasts,
      at least in part through a higher translocation of GLUT4 from the intracellular
      compartment as well as a reduction of GLUT4 internalization, resulting in
      increased glucose uptake. 

PMID- 24108389
TI  - Effects of the selective estrogen receptor modulator ospemifene on bone in rats.
AB  - Ospemifene is a non-estrogen agent that exerts tissue-specific estrogen agonistic
      and weak antagonistic effects (i. e., is a selective estrogen receptor modulator
      [SERM]). The effects of various once-daily oral doses of ospemifene on bone are
      examined across 3 studies for 4 or 52 weeks after surgery in the ovariectomized
      (OVX) rat model of postmenopausal bone loss. Ospemifene treatment reduced the
      loss of bone mineral content and density observed in untreated OVX rats,
      significantly increased distal femur bone mineral content at 51 weeks at 25 mg/kg
      dose compared with untreated OVX rats (p<0.01), and significantly increased
      trabecular bone mineral density of the distal femur and proximal tibia with 1, 5,
      or 25 mg/kg doses after 52 weeks. Ospemifene 5 and 25 mg/kg preserved distal
      femur trabecular structure; trabecular number was significantly increased,
      whereas trabecular separation and eroded surface values were significantly
      decreased (all p<0.01). Structural changes associated with ospemifene were
      accompanied by increased mechanical strength of femurs and 4th lumbar vertebra
      compared with untreated OVX rats. Ospemifene 10 mg/kg prevented OVX-induced bone
      loss; trabecular bone volume of distal femurs was increased after 4 weeks.
      Further, histomorphometric measures revealed decreased bone resorption after 4
      weeks of ospemifene treatment, with effects similar to other SERMs (raloxifene
      and droloxifene). Ospemifene 3 and 10 mg/kg significantly inhibited OVX-induced
      increases in osteoclast number, and doses >=0.3 mg/kg dose-dependently reversed
      the OVX-induced increase in the double-labeled volume:bone volume ratio. These
      results demonstrate antiresorptive, selective agonist effects of ospemifene on
      bone that appear similar to raloxifene in this in vivo animal model of estrogen
      deficiency. 

PMID- 24108390
TI  - Inhibitory effect of submaximal doses of ghrelin on gonadotropin secretion in
      women.
AB  - The effect of ghrelin on gonadotropin secretion has been equivocal. Recent data
      have shown an inhibitory effect of repeated injections of ghrelin on nocturnal LH
      and FSH secretion in women. The aim of this study was to investigate the effect
      of submaximal doses of ghrelin on the diurnal secretion of gonadotropins. Ten
      normally cycling women received 2 consecutive dosages of ghrelin (0.15 MUg/kg and
      0.30 MUg/kg) intravenously in the early and late follicular phases of the cycle.
      Saline was injected in the preceding cycle. Blood samples in relation to ghrelin
      or saline administration (time 0 and 90 min) were taken at -15, 0, 30, 90, 120,
      150, and 180 min. Serum estradiol concentrations were significantly higher in the
      late than in the early follicular phase. Following ghrelin administration, serum
      LH and FSH levels decreased significantly, in relation to the saline injection,
      in the late (p<0.01), although FSH values showed a within the group decrease also
      in the early follicular phase (p<0.05). The study suggests a differential action
      of ghrelin on diurnal gonadotropin secretion throughout the follicular phase of
      the cycle.

PMID- 24108391
TI  - A mechanism underlying hypertensive occurrence in the metabolic syndrome:
      cooperative effect of oxidative stress and calcium accumulation in vascular
      smooth muscle cells.
AB  - Several lines of evidence indicate that reactive oxygen species (ROS)
      overproduction under the metabolic syndrome condition is the leading cause of
      cardiovascular events. Calcium is an important stimulus for vasoconstriction and
      plays a pivotal role in the development of hypertension. Here, we investigate
      whether a relationship exists between metabolic syndrome-induced mitochondrial
      ROS overproduction and Ang II-mediated Ca2+ release in vascular smooth muscle
      cells (VSMC). The effect of mitochondrial ROS on AT1 expression, and Ca2+ and IP3
      generation was studied in 2 VSMC models of metabolic syndrome using fura-2/AM
      probes and ELISA-based assay. Ang II-mediated aortic ring contraction in SD rats
      fed with high-fat diet (HFD) was measured using a force transducer connected to
      chart recorder. In the metabolic syndrome, almost 2-fold increased mitochondrial
      O2 - significantly upregulated AT1 expressions by ~60%, companied by elevated
      Ca2+ and IP3 levels in VSMC and enhanced aortic rings contraction. All these
      increments were blocked by rotenone (inhibitor of mitochondrial respiratory chain
      complex I), ruthenium red (inhibitor of calcium uniporter), cyclosporin A
      (inhibitor of mitochondrial permeability pore), and N-acetylcysteine. Therefore,
      in the states of metabolic syndrome, ROS overproduction in mitochondrial complex
      I enhances Ang II-mediated vascular contraction via an AT1-dependent pathway. In
      addition, the import of Ca2+ from endoplasmic reticulum to mitochondria via
      calcium uniporter and mitochondrial permeability pore seems to serve as a
      mechanism to further aggravate mitochondrial damage and vascular dysfunction that
      may contribute to the occurrence of hypertension. 

PMID- 24108392
TI  - Cost effectiveness of radiofrequency microremodeling for stress urinary
      incontinence.
AB  - INTRODUCTION AND HYPOTHESIS: Stress urinary incontinence (SUI) is a common and
      growing problem among adult women and affects individuals and society through
      decreased quality of life (QoL), decreased work productivity, and increased
      health care costs. A new, nonsurgical treatment option has become available for
      women who have failed conservative therapy, but its cost effectiveness has not
      been evaluated. This study examined the cost effectiveness of transurethral
      radiofrequency microremodeling of the female bladder neck and proximal urethra
      compared with synthetic transobturator tape (TOT), retropubic transvaginal tape
      (TVT) sling, and Burch colposuspension surgeries for treating SUI. METHODS: A
      Markov model was used to compare the cost effectiveness of five strategies for
      treating SUI for patients who had previously failed conservative therapy. The
      strategies were designed to compare the value of starting with a less invasive
      treatment. The cost-effectiveness analysis was conducted from the health care
      system perspective. Efficacy and adverse event rates were obtained from the
      literature; reimbursement costs were based on Medicare fee schedule. The model
      cycle was 3 months, with a 3-year time horizon. Single-variable sensitivity
      analyses were conducted to assess stability of base-case results. RESULTS: Two of
      the five strategies employed the use of transurethral radiofrequency
      microremodeling and achieved 17-30 % lower mean costs relative to their
      comparative sling or Burch strategies. CONCLUSIONS: Superior safety and cost
      effectiveness are recognized when patients are offered a sequential approach to
      SUI management that employs transurethral radiofrequency microremodeling before
      invasive surgical procedures. This sequential approach is consistent with
      treatment strategies for other conditions and offers a solution for women with
      SUI who want to avoid the inherent risks and costs of invasive continence
      surgery.

PMID- 24108393
TI  - Time resolved study of cell death mechanisms induced by amine-modified
      polystyrene nanoparticles.
AB  - Positively charged polymers and nanoparticles (NPs) can be toxic to cells in
      various systems. Using human astrocytoma cells, we have previously shown that 50
      nm amine-modified polystyrene NPs damage mitochondria and induce cell death by
      apoptosis. Here we provide comprehensive details of the cellular events occurring
      after exposure to the NPs in a time-resolved manner. We demonstrate that the
      accumulation of NPs in lysosomes plays a central role in the observed cell death,
      leading to swelling of the lysosomes and release of cathepsins into the cytosol,
      which ultimately propagates the damage to the mitochondria with subsequent
      activation of apoptosis. This is accompanied and sustained by other events, such
      as increasing ROS levels and autophagy. Using various inhibitors, we also show
      the interplay between apoptosis and autophagy as a response to NP accumulation in
      lysosomes. 

PMID- 24108394
TI  - Independent modulation of engagement and connectivity of the facial network
      during affect processing by CACNA1C and ANK3 risk genes for bipolar disorder.
AB  - IMPORTANCE: Genome-wide association studies (GWASs) indicate that single
      nucleotide polymorphisms in the CACNA1C and ANK3 genes increase the risk for
      bipolar disorder (BD). The genes influence neuronal firing by modulating calcium
      and sodium channel functions, respectively. Both genes modulate gamma
      aminobutyric acid-transmitting interneuron function and can thus affect brain
      regional activation and interregional connectivity. OBJECTIVE: To determine
      whether the genetic risk for BD associated with 2 GWAS-supported risk single
      nucleotide polymorphisms at CACNA1C rs1006737 and ANK3 rs10994336 is mediated
      through changes in regional activation and interregional connectivity of the
      facial affect-processing network. DESIGN, SETTING, AND PARTICIPANTS: Cross
      sectional functional magnetic resonance imaging study at a research institute of
      41 euthymic patients with BD and 46 healthy participants, all of British white
      descent. MAIN OUTCOMES AND MEASURES: Blood oxygen level-dependent signal and
      effective connectivity measures during the facial affect-processing task.
      RESULTS: In healthy carriers, both genetic risk variants were independently
      associated with increased regional engagement throughout the facial affect
      processing network and increased effective connectivity between the visual and
      ventral prefrontal cortical regions. In contrast, BD carriers of either genetic
      risk variant exhibited pronounced reduction in ventral prefrontal cortical
      activation and visual-prefrontal effective connectivity. CONCLUSIONS AND
      RELEVANCE: Our data demonstrate that the effect of CACNA1C rs1006737 and ANK3
      rs10994336 (or genetic variants in linkage disequilibrium) on the brain converges
      on the neural circuitry involved in affect processing and provides a mechanism
      linking BD to genome-wide genetic risk variants.

PMID- 24108395
TI  - Schiff bases: a short survey on an evergreen chemistry tool.
AB  - The review reports a short biography of the Italian naturalized chemist Hugo
      Schiff and an outline on the synthesis and use of his most popular discovery: the
      imines, very well known and popular as Schiff Bases. Recent developments on their
      "metallo-imines" variants have been described. The applications of Schiff bases
      in organic synthesis as partner in Staudinger and hetero Diels-Alder reactions,
      as "privileged" ligands in the organometallic complexes and as biological active
      Schiff intermediates/targets have been reported as well. 

PMID- 24108396
TI  - The Piancatelli rearrangement: new applications for an intriguing reaction.
AB  - Nearly forty years ago, at the University of Rome, Giovanni Piancatelli and co
      workers discovered the acid-catalyzed water-mediated rearrangement of 2
      furylcarbinols into 4-hydroxycyclopentenones. These motifs are core components of
      several pharmacologically active compounds and precursors of many natural
      products. The main features of this reaction are the simple experimental
      conditions, the stereochemical outcome and the generality of the procedure.
      Consequently, a re-emergence of this reaction has been seen recently, including
      developments of the Piancatelli rearrangement with some interesting inter- and
      intramolecular variants. This review will mainly focus on the general aspects of
      the reaction along with its more recent applications. 

PMID- 24108397
TI  - Anti-plasmodial activity of some Zulu medicinal plants and of some triterpenes
      isolated from them.
AB  - Mimusops caffra E. Mey. ex A.DC and Mimusops obtusifolia Lam (both members of the
      Sapotaceae family), and Hypoxis colchicifolia Bak (family Hypoxidaceae) are used
      by traditional healers in Zululand to manage malaria. Anti-plasmodial
      investigation of the crude extracts and some triterpenes isolated from the plants
      showed activity against a chloroquine sensitive (CQS) strain of Plasmodium
      falciparum (D10). Among the crude extracts the leaves of M. caffra exhibited the
      highest activity, with an IC50 of 2.14 MUg/mL. The pentacyclic tritepenoid
      ursolic acid (1), isolated from the leaves of M. caffra was the most active
      compound (IC50 6.8 MUg/mL) as compared to taraxerol (2) and sawamilletin (3)
      isolated from the stem bark of M. obtusifolia (IC50 > 100). Chemical modification
      of the ursolic acid (1) to 3beta-acetylursolic acid (4) greatly enhanced its anti
      plasmodial activity. Compound 4 reduced parasitaemia against Plasmodium berghei
      by 94.01% in in vivo studies in mice. The cytotoxicity of 3beta-acetylursolic
      acid (IC50) to two human cell lines (HEK293 and HepG2) was 366.00 MUg/mL and
      566.09 MUg/mL, respectively. The results validate the use of these plants in folk
      medicine.

PMID- 24108398
TI  - Characterization and determination of 2-(2-phenylethyl)chromones in agarwood by
      GC-MS.
AB  - Agarwood is the fragrant resinous heartwood obtained from certain trees in the
      genus Aquilaria belonging to the family Thymelaeaceae. 2-(2-Phenylethyl)chromones
      and characteristic sesquiterpenes are the main classes of aromatic compounds
      isolated from agarwood. Although there are many sesquiterpenes, relatively few 2
      (2-phenylethyl)chromones have been determined in agarwood by GC-MS. After
      analysis of the MS spectra of eighteen 2-(2-phenylethyl)chromone derivatives
      isolated from agarwood and identified by NMR spectroscopy, together with the
      reported MS data and characteristic of structures of 2-(2-phenylethyl)chromones,
      the MS characterization, fragmentation patterns and characteristic fragment peaks
      for the compounds were deduced and a table summarizing MS characterization of 2
      (2-phenylethyl)chromones in agarwood is presented. All the 2-(2
      phenylethyl)chromones previously reported in agarwood are substituted by methoxy
      or/and hydroxy groups, except for one compound. Due to the fact they all possess
      the same basic skeleton (molecular weight: 250) and similar substituent groups
      (methoxy or hydroxy groups), a formula (30m + 16n = MW - 250) is provided to
      calculate the number of methoxy (m) or hydroxy (n) groups according to molecular
      ion peak or molecular weight (MW). We deduced that the characteristic
      fragmentation behaviors of the 2-(2-phenylethyl)chromones are the cleavages of
      the CH2-CH2 bond between chromone moiety and phenyl moiety. Thus, characteristic
      fragment ions, such as m/z 91 [C7H7], 107 [C7H6+OH], 121 [C7H6+OCH3], 137
      [C7H5+OH+OCH3] are formed by different substituted benzyl moieties, while
      characteristic fragment ions such as m/z 160 [C10H8O2], 176 [C10H7O2+OH], 190
      [C10H7O2+OCH3], 220 [C10H6O2+OCH3*2] are formed by different substituted chromone
      moieties. Furthermore, rules regarding to the relationship between the positions
      of hydroxy or methoxy groups and the relative abundances of benzyl and chromone
      fragment ions have been deduced. Elucidation of how the positions of hydroxy or
      methoxy groups affect the relative abundances of benzyl and chromone fragment
      peaks is also provided. Fifteen unidentified compounds of an artificial agarwood
      sample analyzed by GC-MS, were preliminary determined as 2-(2
      phenylethyl)chromones by analysis of their MS characterization and by comparison
      of their MS spectra with those of 18 standard compounds or 2-(2
      phenylethyl)chromones reported in literature according to the above-mentioned
      methods and rules. This report will be helpful for the analysis and structural
      elucidation of 2-(2-phenylethyl)chromones in agarwood by GC-MS, and provides fast
      and reliable characterization of the quality of agarwood.

PMID- 24108399
TI  - Synthesis of boron-containing primary amines.
AB  - In this study, boron-containing primary amines were synthesized for use as
      building blocks in the study of peptoids. In the first step, Gabriel synthesis
      conditions were modified to enable the construction of seven different
      aminomethylphenyl boronate esters in good to excellent yields. These compounds
      were further utilized to build peptoid analogs via an Ugi four-component reaction
      (Ugi-4CR) under microwave irradiation. The prepared Ugi-4CR boronate esters were
      then successfully converted to the corresponding boronic acids. Finally, the
      peptoid structures were successfully modified by cross-coupling to
      aryl/heteroaryl chlorides via a palladium-mediated Suzuki coupling reaction to
      yield the corresponding derivatives in moderate to good yields. 

PMID- 24108400
TI  - G-quadruplex structures in the human genome as novel therapeutic targets.
AB  - G-quadruplexes are secondary structures that may form within guanine-rich nucleic
      acid sequences. Telomeres have received much attention in this regard since they
      can fold into several distinct intramolecular G-quadruplexes, leading to the
      rational design and development of G-quadruplex-stabilizing molecules. These
      ligands were shown to selectively exert an antiproliferative and chemosensitizing
      activity in in vitro and in vivo tumor models, without appreciably affecting
      normal cells. Such findings point to them as possible drug candidates for
      clinical applications. Other than in telomeres, G-quadruplexes may form at
      additional locations in the human genome, including gene promoters and
      untranslated regions. For instance, stabilization of G-quadruplex structures
      within the promoter of MYC, KIT, or KRAS resulted in the down-regulation of the
      corresponding oncogene either in gene reporter assays or in selected experimental
      models. In addition, the alternative splicing of a number of genes may be
      affected for a therapeutic benefit through the stabilization of G-quadruplexes
      located within pre-mRNAs. It is now emerging that G-quadruplex structures may act
      as key regulators of several biological processes. Consequently, they are
      considered as attractive targets for broad-spectrum anticancer therapies, and
      much effort is being made to develop a variety of ligands with improved G
      quadruplex recognition properties. Quarfloxin, a fluoroquinolone derivative
      designed to target a G-quadruplex within ribosomal DNA and disrupt protein-DNA
      interactions, has entered clinical trials for different malignancies. This review
      will provide some hints on the role of G-quadruplex structures in biological
      processes and will evaluate their implications as novel therapeutic targets. 

PMID- 24108401
TI  - The involvement of amino acid side chains in shielding the nickel coordination
      site: an NMR study.
AB  - Coordination of proteins and peptides to metal ions is known to affect their
      properties, often by a change in their structural organization. Side chains of
      the residues directly involved in metal binding or very close to the coordination
      centre may arrange themselves around it, in such a way that they can, for
      instance, disrupt the protein functions or stabilize a metal complex by shielding
      it from the attack of water or other small molecules. The conformation of these
      side chains may be crucial to different biological or toxic processes. In our
      research we have encountered such behaviour in several cases, leading to
      interesting results for our purposes. Here we give an overview on the structural
      changes involving peptide side chains induced by Ni(II) coordination. In this
      paper we deal with a number of peptides, deriving from proteins containing one or
      more metal coordinating sites, which have been studied through a series of NMR
      experiments in their structural changes caused by Ni(II) complexation. Several
      peptides have been included in the study: short sequences from serum albumin
      (HSA), Des-Angiotensinogen, the 30-amino acid tail of histone H4, some fragments
      from histone H2A and H2B, the initial fragment of human protamine HP2 and
      selected fragments from prion and Cap43 proteins. NMR was the election technique
      for gathering structural information. Experiments performed for this purpose
      included 1D 1H and 13C, and 2D HSQC, COSY, TOCSY, NOESY and ROESY acquisitions,
      which allowed the calculation of the Ni(II) complexes structural models.

PMID- 24108402
TI  - Mechanical, rheological and release behaviors of a poloxamer 407/ poloxamer
      188/carbopol 940 thermosensitive composite hydrogel.
AB  - The aims of this study were to prepare a thermosensitive composite hydrogel (TCH)
      by mixing 24% (w/v) poloxamer 407 (P407), 16% (w/v) poloxamer 188 (P188) and 0.1%
      (w/v) carbopol 940 (C940), and to determine the effect of natural borneol/ (2
      hydroxypropyl)-beta-cyclodextrin (NB/HP-beta-CD) inclusion complex on the phase
      transition temperature, mechanical, rheological properties, and release behaviors
      of the TCH using the tube inversion method, a texture analyzer, a rheometer, and
      in vitro release , respectively. The results showed that as the concentration of
      NB/HP-beta-CD increased, the phase transition temperature of the TCH was
      increased from 37.26 to 38.34  degrees C and the mechanical properties of the TCH
      showed that the hardness, cohesiveness, strength, and adhesiveness were increased
      from 0.025 to 0.064 kg, 0.022 to 0.064 kg, 0.110 to 0.307 kg and 0.036 to 0.105
      kg, respectively, but the rheological properties of the TCH showed that G', G''
      and eta were decreased from 7,760 to 157.50 Pa, 1,274 to 36.28 Pa and 1,252 to
      25.37 Pas, respectively. The in vitro release showed that an increasing NB/HP
      beta-CD concentration decreased the release rate of NB from the TCH, but the
      amount of NB released was more than 96% at 60 min, which showed the TCH had good
      release behavior. 

PMID- 24108403
TI  - Barefoot running: an evaluation of current hypothesis, future research and
      clinical applications.
AB  - Barefoot running has become a popular research topic, driven by the increasing
      prescription of barefoot running as a means of reducing injury risk. Proponents
      of barefoot running cite evolutionary theories that long-distance running ability
      was crucial for human survival, and proof of the benefits of natural running.
      Subsequently, runners have been advised to run barefoot as a treatment mode for
      injuries, strength and conditioning. The body of literature examining the
      mechanical, structural, clinical and performance implications of barefoot running
      is still in its infancy. Recent research has found significant differences
      associated with barefoot running relative to shod running, and these differences
      have been associated with factors that are thought to contribute to injury and
      performance. Crucially, long-term prospective studies have yet to be conducted
      and the link between barefoot running and injury or performance remains tenuous
      and speculative. The injury prevention potential of barefoot running is further
      complicated by the complexity of injury aetiology, with no single factor having
      been identified as causative for the most common running injuries. The aim of the
      present review was to critically evaluate the theory and evidence for barefoot
      running, drawing on both collected evidence as well as literature that have been
      used to argue in favour of barefoot running. We describe the factors driving the
      prescription of barefoot running, examine which of these factors may have merit,
      what the collected evidence suggests about the suitability of barefoot running
      for its purported uses and describe the necessary future research to confirm or
      refute the barefoot running hypotheses. 

PMID- 24108404
TI  - A ZnFe2O4-ZnO nanorod array p-n junction composite and its photoelectrochemical
      performance.
AB  - A ZnFe2O4-ZnO nanorod array (NRA) with a three-dimensional network nanometer
      structure was prepared. The photoelectrochemical performance of the ZnFe2O4-ZnO
      NRA composite is significantly improved due to the formation of a p-n
      heterojunction electric field at the interface between ZnFe2O4 and ZnO, the
      increase of the overall utilization efficiency of incident light energy, and the
      visible light absorption capability of ZnFe2O4. 

PMID- 24108405
TI  - Resistance to RAF inhibitors revisited.
AB  - In early 2011, we reviewed the initial success of the RAF inhibitor vemurafenib
      in mutant V600 BRAF melanoma patients. It was soon evident that the response to
      RAF inhibitor is heterogeneous and that the short-term benefits are burdened by
      the development of resistance. The field has progressed rapidly with the Food and
      Drug Administration approval of vemurafenib and the development of other RAF and
      MEK (mitogen-activated protein kinase/extracellular signal-regulated kinase)
      inhibitors. Despite these advances, the issue of RAF inhibitor resistance
      remains. Here, we review recent clinical advances in the field, the growing
      number of resistance mechanisms, preclinical evidence for combinatorial trials
      using RAF inhibitors as the building blocks, and the new challenges that are
      arising. 

PMID- 24108407
TI  - A systematic review and meta-analysis of the evidence base for add-on treatment
      for patients with major depressive disorder who have not responded to
      antidepressant treatment: a European perspective.
AB  - Previous comparative reviews of add-on therapies for patients with major
      depressive disorder (MDD) with an inadequate response to antidepressants have not
      used meta-analytic techniques to compare different drug classes and have included
      non-licensed therapies. This meta-analysis reviewed all published peer-reviewed
      evidence for the efficacy of EU-licensed therapies in patients with MDD and an
      inadequate response to antidepressant monotherapy. Papers concerning randomized
      clinical trials (RCTs) were identified using criteria from the Cochrane Handbook
      for Systematic Reviews of Interventions. Add-on therapies reviewed were
      antidepressants, quetiapine XR, lithium, and S-adenosyl-l-methionine (SAMe).
      Seven RCTs that reported response and remission in a way that allowed
      quantitative analysis were included in this meta-analysis. Comparison of the
      different drug classes indicated that most interventions had similar efficacy.
      The likelihood of response was significantly greater with SAMe versus placebo and
      lithium and with quetiapine XR versus placebo. Most add-on interventions
      demonstrated comparable efficacy in patients with MDD and an inadequate response
      to initial antidepressants. However, there is currently a paucity of high-quality
      data regarding the use of add-on treatments in patients with MDD who are
      inadequate responders to antidepressants, with quetiapine XR presenting the most
      comprehensive evidence base to date. 

PMID- 24108406
TI  - YAP and TAZ regulate skin wound healing.
AB  - The Hippo signaling pathway regulates organ size, tissue regeneration, and stem
      cell self-renewal. The two key downstream transcription coactivators in this
      pathway, Yes-associated protein (YAP) and transcriptional coactivator with PDZ
      binding motif (TAZ), mediate the major gene regulation and biological functions
      of the Hippo pathway. The biological functions of YAP and TAZ in many tissues are
      known; however, their roles in skin wound healing remain unclear. To analyze
      whether YAP and/or TAZ are required for cutaneous wound healing, we performed
      small interfering RNA (siRNA)-mediated knockdown of YAP/TAZ in full-thickness
      skin wounds. YAP is strongly expressed in the nucleus and cytoplasm in the
      epidermis and hair follicle. Interestingly, YAP is expressed in the nucleus in
      the dermis at 2 and 7 days after wounding. TAZ normally localizes to the
      cytoplasm in the dermis but is distributed in both the nucleus and cytoplasm at 1
      day after wounding. The knockdown of YAP and TAZ markedly delayed the rate of
      wound closure and reduced the transforming growth factor-beta1 (TGF-beta1)
      expression in the wound. YAP and TAZ also modulate the expression of TGF-beta1
      signaling pathway components such as Smad-2, p21, and Smad-7. These results
      suggest that YAP and TAZ localization to the nucleus is required for skin wound
      healing. 

PMID- 24108408
TI  - Tyrosine-free amino acid mixtures reduce physiologically-evoked release of
      dopamine in a selective and activity-dependent manner.
AB  - Depletion of the catecholamine precursor tyrosine using tyrosine-free amino acid
      mixtures is an important tool in neuropsychological studies, and often considered
      dopamine selective on the basis of neuropharmacological studies. However, little
      is known of the effects of tyrosine depletion when catecholamine neurons are
      activated physiologically. Here we investigated the effect of tyrosine-free amino
      acid mixtures on catecholamine release evoked in vivo using a stimulation
      paradigm aimed to approximate the phasic firing pattern of these neurons that
      accompanies cognitive and behavioural change. Dopamine and noradrenaline release
      was monitored by microdialysis in rat medial prefrontal cortex (mPFC) and
      striatum (chloral hydrate anaesthesia, perfusion medium containing 1 uM cocaine).
      Electrical stimulation of the medial forebrain bundle (MFB) caused a short
      lasting, frequency-dependent increase in dopamine and noradrenaline. A full
      tyrosine-free amino acid mixture reduced the release of dopamine in mPFC and
      striatum, across a range of stimulation frequencies, and the effect was greater
      as stimulation frequency increased. Similar results were obtained using a smaller
      tyrosine-free amino acid mixture. In the same experiments showing decreased
      dopamine, neither tyrosine-free mixture of amino acids significantly altered
      stimulation-evoked release of noradrenaline. These results show that tyrosine
      depletion using tyrosine-free amino acid mixtures causes a selective, activity
      dependent decrease in dopamine release when dopamine neurons are driven
      physiologically. 

PMID- 24108409
TI  - Anxiolytic effects of vestipitant in a sub-group of healthy volunteers known to
      be sensitive to CO2 challenge.
AB  - The pharmacological properties of two NK1 antagonists were studied in comparison
      with a benzodiazepine during a 7% CO2 challenge in a population of healthy
      volunteers selected for a high sensitivity to the challenge. In total, 19 healthy
      subjects, pre-screened for their responsiveness to the 7% CO2 test, took part in
      the randomised, double-blind, cross-over, incomplete block design study. After
      receiving treatment or placebo, the volunteers were subjected to three 7% CO2
      challenges each for a time of 20 min. The treatment consisted of the
      administration of the following three active drugs: a single dose of
      benzodiazepine alprazolam (0.75 mg) and a single dose of the NK1 antagonists
      vestipitant (GW597599) (15 mg) and vofopitant (GR205171) (25 mg). Anxiety during
      the challenge was evaluated with Visual Analogue Scale-Anxiety (VAS-A) and with
      Panic Symptom List (PSL III-R). Respiratory parameters, heart rate and skin
      conductance were also recorded. Compared with placebo, vestipitant showed a
      significant reduction (p<0.05) in anxiety assessed on the VAS-A scale (DeltaVAS
      A%) while alprazolam significantly (p<0.01) attenuated the PSL III-R total score.
      Vofopitant did not show any anxiolytic effect. In the comparison analysis between
      placebo and drugs, none of the respiratory and other physiological parameters
      showed a statistically significant difference. 

PMID- 24108410
TI  - Limited central side effects of a beta-subunit subtype-selective GABAA receptor
      allosteric modulator.
AB  - GABAergic anxiolytics have well-documented centrally mediated side effects
      including sedation, potentiation of ethanol, tolerance, abuse liability and
      memory impairment. Most research directed towards identifying an anxioselective
      GABAergic therapeutic has been based upon the theory that these side effects
      could be mitigated by avoiding alpha1/5-subunit GABAA receptors while
      specifically targeting those with the alpha2/3-subunit. Unfortunately, there are
      prominent exceptions to this theory and it has yet to be translated into clinical
      success. We previously demonstrated that beta2/3-subunit-selective GABAA receptor
      positive allosteric modulators act as anxiolytics with reduced sedation and
      ethanol potentiation regardless of their activity at alpha1-subunit GABAA
      receptors. The prototypical beta2/3-subunit-selective positive allosteric
      modulator, 2-261, is further characterized here for additional side effects
      commonly associated with central GABAA receptor activation. In mice, 10 times the
      anxiolytic dose (10 mg/kg) of 2-261 does not induce behavioral tolerance in the
      elevated plus maze following a 2 week subchronic treatment. In rats, an
      anxiolytic dose (10 mg/kg) of 2-261 is inactive in conditioned place preference,
      suggesting a reduced abuse liability. In rats, 10 times the anxiolytic dose (100
      mg/kg) of 2-261 does not have a significant amnestic effect in the radial arm
      maze, suggesting a greater therapeutic index for memory impairment. These results
      suggest that beta2/3-subunit subtype-selective GABAA receptor-positive allosteric
      modulators not only have reduced sedative liability, but also a reduction in
      other central side effects commonly associated with broader GABAA receptor
      activation. beta2/3-subunit-selective compounds may represent a novel design
      template for anxiolytics with benzodiazepine-like efficacy and mitigated side
      effects. 

PMID- 24108411
TI  - Atomic-scale fingerprint of Mn dopant at the surface of Sr3(Ru1-xMnx)2O7.
AB  - Chemical doping in materials is known to give rise to emergent phenomena. These
      phenomena are extremely difficult to predict a priori, because electron-electron
      interactions are entangled with local environment of assembled atoms. Scanning
      tunneling microscopy and low energy electron diffraction are combined to
      investigate how the local electronic structure is correlated with lattice
      distortion on the surface of Sr3(Ru1-xMnx)2O7, which has double-layer building
      blocks formed by (Ru/Mn)O6 octahedra with rotational distortion. The presence of
      doping-dependent tilt distortion of (Ru/Mn)O6 octahedra at the surface results in
      a C2v broken symmetry in contrast with the bulk C4v counterpart. It also enables
      us to observe two Mn sites associated with the octahedral rotation in the bulk
      through the "chirality" of local electronic density of states surrounding Mn,
      which is randomly distributed. These results serve as fingerprint of chemical
      doping on the atomic scale.

PMID- 24108412
TI  - Photodetachment and photodissociation of the linear OCuO- molecular anion: energy
      and time dependence of Cu- production.
AB  - A photodissociative study of CuO2(-) is presented using a combination of energy
      and time domain photoelectron spectroscopy. Ion source conditions are used that
      solely produce linear OCuO(-). Photodissociation of this isomer to produce Cu(-)
      + O2 is conclusively demonstrated at wavelengths between 765 and 340 nm.
      Nanosecond pulsed photoexcitation at wavelengths shorter than 340 nm produces
      single photon detachment transitions from the first excited state of CuO2(-). At
      longer wavelengths narrow Cu(-) fragment transitions are observed as a result of
      a sequential two photon process. In addition, the longer wavelengths produce a
      weak, broad two photon dependent signal, the result of detachment of the
      dissociating linear isomer. Time resolved pump-probe measurements reveal a long
      timescale growth (up to 150 ps) of the Cu(-) fragment yield, consistent with the
      unfavorable starting geometry for the dissociative process and indicating a
      potential energy surface which has one or more substantial barriers to
      dissociation. 

PMID- 24108413
TI  - Survival and toxicity in patients with disseminated germ cell cancer aged 40
      years and older.
AB  - BACKGROUND: Germ-cell cancer (GCC) patients aged >=40 years have a two-fold
      higher GCC-specific mortality. It has been hypothesized that reduced treatment
      intensity combined with increased treatment related toxicity could be the
      explanation. The objective was to analyze chemotherapy intensity, treatment
      related toxicity and survival in patients aged >=40 years treated with standard
      chemotherapy for GCC compared with a younger control group that received similar
      treatment during the same period. METHODS: From 1984 to 2011, 135 patients aged
      >=40 years with disseminated GCC treated with bleomycin, etoposide and cisplatin
      (BEP). A control-group of 135 patients aged 18-35 years was randomly selected
      matched on year of BEP treatment. Cumulated doses of BEP as well as bone marrow
      toxicity, renal- and lung functions were recorded before, during and after
      termination of treatment. All patients were followed until death or October 1,
      2011. RESULTS: The cumulated doses of BEP were comparable between the two groups,
      however, more patients aged >=40 years were reduced in bleomycin doses based on a
      decrease in carbon monoxide diffusion capacity corrected for haemoglobin (P =
      0.03). No differences between the two groups were found regarding bone marrow
      toxicity or mean percentage changes in lung- or renal function. Patients aged
      >=40 year had increased cancer specific mortality, HR = 4.8 (P = 0.005). In
      particular patients with disease progression after first line chemotherapy had
      increased mortality (P = 0.015). Moreover, the 5-year overall survival for
      patients aged >=40 years was 82.5% compared to the expected 5-year survival of
      the background population of 96.3% (P <0.001). CONCLUSIONS: Treatment related
      toxicity could not explain the increased cancer specific mortality in patients
      aged >=40 years compared to a younger control-group, and while there were no
      differences in the administrated doses of cisplatin/etoposide, a decreased number
      of bleomycin doses were administered in the older patients. Apart from this, the
      inferior prognosis could be related to tumour biology, increased co-morbidity, or
      more severe toxicity in relation to second line treatment.

PMID- 24108414
TI  - Characterization of CYP76AH4 clarifies phenolic diterpenoid biosynthesis in the
      Lamiaceae.
AB  - Miltiradiene (1) is the precursor of phenolic diterpenoids such as ferruginol
      (2), requiring aromatization and hydroxylation. While this has been attributed to
      a single cytochrome P450 (CYP76AH1), characterization of the rosemary ortholog
      CYP76AH4 led to the discovery that these CYPs simply hydroxylate the facilely
      oxidized aromatic intermediate abietatriene (3). 

PMID- 24108415
TI  - Safely and effectively reducing inpatient length of stay: a controlled study of
      the General Internal Medicine Care Transformation Initiative.
AB  - PURPOSE: Whether improving the efficiency of hospital care will worsen post
      discharge outcomes is unclear. We designed this study to evaluate the General
      Internal Medicine (GIM) Care Transformation Initiative implemented at one of the
      seven teaching hospitals in the Canadian province of Alberta. METHODS: Controlled
      before-after study of GIM patients hospitalised at the University of Alberta
      Hospital (UAH, intervention site, n=1896) or the six other teaching hospitals in
      Alberta-three in Edmonton (intra-regional controls (IRC), n=4550) and three in
      Calgary (extra-regional controls (ERC), n=4095). The primary effectiveness
      outcome was risk-adjusted length of stay (LOS) and the primary safety outcome was
      'mortality during index hospitalisation or all-cause readmission or death within
      30-days of discharge'. RESULTS: LOS for GIM patients decreased by 0.68 days at
      Alberta teaching hospitals between 2009 and 2012; GIM patients hospitalised at
      the UAH exhibited a further 20% relative decline in adjusted LOS (total
      reduction=1.43 days, 95% CI 0.94 to 1.92 days) from PRE to POST. Interrupted time
      series (ITS) confirmed that the 1.43 day reduction at the UAH was statistically
      significant (level change p=0.003), while the declines at the IRC (p=0.37) and
      ERC (p=0.45) were not. Our safety outcome did not change for UAH patients (18.4%
      PRE-intervention vs 17.8% POST-intervention, adjusted OR 1.02 (95%CI 0.80 to
      1.31), p=0.42 on ITS), nor for those hospitalised at the IRC (p=0.33) or the ERC
      (p=0.73) sites. CONCLUSIONS: The Care Transformation Initiative was associated
      with substantial reductions in LOS without increasing post-discharge events
      commonly quoted as proxies for quality.

PMID- 24108416
TI  - GalaxyDock2: protein-ligand docking using beta-complex and global optimization.
AB  - In this article, an enhanced version of GalaxyDock protein-ligand docking program
      is introduced. GalaxyDock performs conformational space annealing (CSA) global
      optimization to find the optimal binding pose of a ligand both in the rigid
      receptor mode and the flexible-receptor mode. Binding pose prediction has been
      improved compared to the earlier version by the efficient generation of high
      quality initial conformations for CSA using a predocking method based on a beta
      complex derived from the Voronoi diagram of receptor atoms. Binding affinity
      prediction has also been enhanced by using the optimal combination of energy
      components, while taking into consideration the energy of the unbound ligand
      state. The new version has been tested in terms of binding mode prediction,
      binding affinity prediction, and virtual screening on several benchmark sets,
      showing improved performance over the previous version and AutoDock, on which the
      GalaxyDock energy function is based. GalaxyDock2 also performs better than or
      comparable to other state-of-the-art docking programs. GalaxyDock2 is freely
      available at http://galaxy.seoklab.org/softwares/galaxydock.html.

PMID- 24108417
TI  - [Papilledema, hydrocephalus and diplopia - not a temporal but a causal
      connection?].

PMID- 24108418
TI  - Maternal depression during pregnancy and the postnatal period: risks and possible
      mechanisms for offspring depression at age 18 years.
AB  - IMPORTANCE: Some small studies suggest that maternal postnatal depression is a
      risk factor for offspring adolescent depression. However, to our knowledge, no
      large cohort studies have addressed this issue. Furthermore, only 1 small study
      has examined the association between antenatal depression and later offspring
      depression. Understanding these associations is important to inform prevention.
      OBJECTIVE: To investigate the hypothesis that there are independent associations
      between antenatal and postnatal depression with offspring depression and that the
      risk pathways are different, such that the risk is moderated by disadvantage (low
      maternal education) with postnatal depression but not with antenatal depression.
      DESIGN, SETTING, AND PARTICIPANTS: Prospective investigation of associations
      between symptoms of antenatal and postnatal parental depression with offspring
      depression at age 18 years in a UK community-based birth cohort (Avon
      Longitudinal Study of Parents and Children) with data from more than 4500 parents
      and their adolescent offspring. MAIN OUTCOMES AND MEASURES: Diagnosis of
      offspring aged 18 years with major depression using the International
      Classification of Diseases, 10th Revision. RESULTS: Antenatal depression was an
      independent risk factor. Offspring were 1.28 times (95% CI, 1.08-1.51; P = .003)
      more likely to have depression at age 18 years for each standard deviation
      increase in maternal depression score antenatally, independent of later maternal
      depression. Postnatal depression was also a risk factor for mothers with low
      education, with offspring 1.26 times (95% CI, 1.06-1.50; P = .01) more likely to
      have depression for each standard deviation increase in postnatal depression
      score. However, for more educated mothers, there was little association (odds
      ratio, 1.09; 95% CI, 0.88-1.36; P = .42). Analyses found that maternal education
      moderated the effects of postnatal but not antenatal depression. Paternal
      depression antenatally was not associated with offspring depression, while
      postnatally, paternal depression showed a similar pattern to maternal depression.
      CONCLUSIONS AND RELEVANCE: The findings suggest that treating maternal depression
      antenatally could prevent offspring depression during adulthood and that
      prioritizing less advantaged mothers postnatally may be most effective.

PMID- 24108419
TI  - Decoration of electrospun nanofibers with monomeric catechols to facilitate cell
      adhesion.
AB  - Monomeric catechols are displayed on the surface of polymeric nanofibers by
      robust catechol-thiol interactions to enhance cell adhesion and migration.
      Dihydroxyphenyl propionic acid is chemically conjugated to primary amine groups
      of poly(epsilon-caprolactone)-poly(ethylene glycol)-amine (PCL-PEG) nanofibers to
      display catechol moieties on the surface. At basic pH, catecholized nanofibers
      incorporate thiol groups at a five-fold higher rate than at acidic pH, while
      catechol-coated surfaces do not show any pH-dependent binding. Live/dead cell
      staining indicates that the catecholized nanofibers do not exert any cytotoxic
      effects. Also, NIH 3T3 cells cultured on the catecholized nanofibers show
      increased attachment and migration that is proportional to the amount of the
      immobilized catechol moieties on the surface. These results clearly indicate that
      6 nmol of monomeric catechols on the surface of nanofiber can promote cell
      adhesion and migration by thiol-catehol interactions. 

PMID- 24108420
TI  - Highly efficient deep-blue emitters based on cis and trans N-heterocyclic carbene
      Pt(II) acetylide complexes: synthesis, photophysical properties, and mechanistic
      studies.
AB  - We have synthesized cis and trans N-heterocyclic carbene (NHC) platinum(II)
      complexes bearing sigma-alkynyl ancillary ligands, namely [Pt(dbim)2 (C?CR)2 ]
      [DBIM=N,N'-didodecylbenzimidazoline-2-ylidene; R=C6 H4 F (4), C6 H5 (5), C6 H2
      (OMe)3 (6), C4 H3 S (7), and C6 H4 C?CC6 H5 (8)] and [Pt(ibim)2 (C?CC6 H5 )2 ]
      (9) (ibim=N,N'-diisopropylbenzimidazoline-2-ylidene), starting from
      [Pt(cod)(C?CR)2 ] (COD=cyclooctadiene) and 2 equivalents of [dbimH]Br ([ibimH]Br
      for complexes 9) in the presence of tBuOK and THF. Mechanistic investigations
      aimed at uncovering the cis to trans isomerization reaction have been performed
      on the representative cis complex 5 a [Pt(dbim)2 (C?CC6 H5 )2 ] and revealed the
      isomerization to progress smoothly in good yield when 5 a was treated with
      catalytic amounts of [Pt(cod)(C?CR)2 ] at 75  degrees C in THF or when 5 a was
      heated at 200  degrees C in the solid state under an inert atmosphere. Detailed
      examination of the reactions points to the possible involvement, in a catalytic
      fashion, of a solvent-stabilized Pt(II) dialkyne complex in the former case and a
      Pt(0) NHC complex in the latter case, for the transformation of the cis isomer to
      the corresponding trans complex. Thermal stability and the isomerization process
      in the solid state have been further investigated on the basis of TGA and DSC
      measurements. X-ray diffraction studies have been carried out to confirm the
      solid-state structures of 4 b, 5 a, 5 b, and 9 b. All of the synthesized dialkyne
      complexes 4-9 exhibit phosphorescence in solution, in the solid state at room
      temperature (RT), and also in frozen solvent glasses at 77 K. The emission
      wavelengths and quantum yields have been found to be highly tunable as a function
      of the alkynyl ligand. In particular, the trans isomer of complex 9 in a spin
      coated film (10 wt % in poly(methyl methacrylate), PMMA) exhibits a high
      phosphorescence quantum yield of 80 %, which is the highest reported for Pt(II) 
      based deep-blue emitters. Experimental observations and time-dependent density
      functional theory (TD-DFT) calculations are strongly indicative of the emission
      being mainly governed by metal-perturbed interligand ((3) IL) charge transfer. 

PMID- 24108423
TI  - Homogeneous visible-light photoredox catalysis.

PMID- 24108424
TI  - Titanium dioxide@polypyrrole core-shell nanowires for all solid-state flexible
      supercapacitors.
AB  - Herein, we developed a facile two-step process to synthesize TiO2@PPy core-shell
      nanowires (NWs) on carbon cloth and reported their improved electrochemical
      performance for flexible supercapacitors (SCs). The fabricated solid-state SC
      device based on TiO2@PPy core-shell NWs not only has excellent flexibility, but
      also exhibits remarkable electrochemical performance. 

PMID- 24108425
TI  - MPTP-induced dopamine neuron degeneration and glia activation is potentiated in
      MDMA-pretreated mice.
AB  - Clinical observations report a greater propensity to develop Parkinson's disease
      (PD) in amphetamine users. 3,4-Methylenedioxymethamphetamine (MDMA; "ecstasy") is
      an amphetamine-related drug that is largely consumed by adolescents and young
      adults, which may have neuroinflammatory and neurotoxic effects. Here, the
      objective was to evaluate in mice whether consumption of MDMA during adolescence
      might influence the neuroinflammatory and neurotoxic effects of 1-methyl-4-phenyl
      1,2,3,6-tetrahydropyridine (MPTP), a toxin known to induce PD in humans. The
      activation of astroglia and microglia by glial fibrillary acidic protein (GFAP)
      and complement receptor type 3 (CD11b) immunohistochemistry and the degeneration
      of dopaminergic neurons by tyrosine hydroxylase (TH) immunohistochemistry were
      evaluated. MPTP (20 mg/kg * 4) was administered to mice treated from ages 8 weeks
      to 17 weeks with MDMA (10 mg/kg twice daily, two times a week). In mice that were
      chronically treated with MDMA, administration of MPTP induced a higher microglial
      and astroglial response in both the striatum and the substantia nigra pars
      compacta (SNc) compared with vehicle-treated or vehicle + MPTP-treated mice.
      Inflammatory changes were associated with a decrease in TH immunoreactivity in
      the SNc of MDMA-treated mice and with a further decrease in the striatum and the
      SNc of MDMA + MPTP-treated mice compared with vehicle-treated, MDMA-treated, and
      MPTP-treated mice. The results demonstrate that chronic administration of MDMA
      during late adolescence in mice exacerbates the neurodegeneration and
      neuroinflammation caused by MPTP, suggesting that MDMA may constitute a risk
      factor for dopaminergic neuron degeneration.

PMID- 24108426
TI  - Robust Kalman filtering cooperated Elman neural network learning for vision
      sensing-based robotic manipulation with global stability.
AB  - In this paper, a global-state-space visual servoing scheme is proposed for
      uncalibrated model-independent robotic manipulation. The scheme is based on
      robust Kalman filtering (KF), in conjunction with Elman neural network (ENN)
      learning techniques. The global map relationship between the vision space and the
      robotic workspace is learned using an ENN. This learned mapping is shown to be an
      approximate estimate of the Jacobian in global space. In the testing phase, the
      desired Jacobian is arrived at using a robust KF to improve the ENN learning
      result so as to achieve robotic precise convergence of the desired pose.
      Meanwhile, the ENN weights are updated (re-trained) using a new input-output data
      pair vector (obtained from the KF cycle) to ensure robot global stability
      manipulation. Thus, our method, without requiring either camera or model
      parameters, avoids the corrupted performances caused by camera calibration and
      modeling errors. To demonstrate the proposed scheme's performance, various
      simulation and experimental results have been presented using a six-degree-of
      freedom robotic manipulator with eye-in-hand configurations. 

PMID- 24108428
TI  - Clinical judgement heuristics: methods and models.

PMID- 24108430
TI  - Glomangiomatosis of the sural nerve.

PMID- 24108429
TI  - Profile of changes in bone turnover markers during once-weekly teriparatide
      administration for 24 weeks in postmenopausal women with osteoporosis.
AB  - SUMMARY: Changes in bone turnover markers with weekly 56.5 MUg teriparatide
      injections for 24 weeks were investigated in women with osteoporosis. Changes in
      bone turnover markers 24 h after each injection of teriparatide were constant.
      During the 24 week period, bone formation markers increased and baseline bone
      resorption marker levels were maintained. INTRODUCTION: This study aimed to
      clarify the changes in bone turnover markers during 24 weeks of once-weekly
      teriparatide injections in postmenopausal women with osteoporosis. METHODS: The
      24 h changes in pharmacokinetics (PK), calcium metabolism, and bone turnover
      markers (serum osteocalcin, procollagen type I N-terminal propeptide (P1NP),
      urinary cross-linked N-telopeptide of type I collagen (NTX), deoxypiridinoline
      (DPD)) after each injection of 56.5 MUg teriparatide at the data collection weeks
      (0, 4, 12, and 24 weeks) were investigated. The changes were evaluated by
      comparison with the data at 0 h in each data collection week. RESULTS: Similar 24
      h changes in each parameter after injection of teriparatide were observed in each
      data collection week. Serum calcium increased transiently, and intact PTH
      decreased 4-8 h after injection; serum calcium subsequently returned to baseline
      levels. Calcium and intact PTH levels decreased for 24 weeks. Although serum
      osteocalcin decreased at 24 h, it was significantly increased at 4 weeks. P1NP
      decreased transiently and then increased significantly at 24 h. P1NP was
      significantly increased at 4 weeks. Urinary NTX and DPD were significantly
      increased transiently and then decreased at 24 h. The urinary DPD level decreased
      significantly at 4 weeks. CONCLUSIONS: Twenty-four hour changes in PK, calcium
      metabolism, and bone turnover markers showed the same direction and level after
      once-weekly teriparatide injections for 24 weeks, with no attenuation of the
      effect over time. After 24 weeks, the bone formation marker, serum osteocalcin,
      increased significantly, but the serum P1NP, did not. Bone resorption markers
      decreased or remained the same.

PMID- 24108431
TI  - Changing frequency of equivocal HER-2/neu scores and factors predictive of
      negative HER 2/neu fluorescent in situ hybridisation in invasive carcinomas of
      the breast.
AB  - BACKGROUND: Analysis of human epidermal growth factor receptor 2 (HER-2) status
      has become standard of care in breast cancer patients due to its important
      prognostic and therapeutic implications. Immunohistochemistry (IHC) is the most
      commonly used primary method for detection of HER-2 overexpression. Controversy
      exists on the interpretation of samples that are equivocal for HER 2 status (IHC
      2+). Recent guidelines state that samples equivocal for HER 2 status require
      validation with fluorescent in situ hybridisation (FISH). The use of FISH,
      however, despite higher accuracy comes at a higher cost that is not affordable to
      all patients. METHODS: This study is a retrospective study conducted at the
      American University of Beirut Medical Center, including women diagnosed with
      breast cancer with equivocal IHC scores presenting between 2009 and 2011. We
      attempted to correlate clinicopathological characteristics of patients diagnosed
      with breast cancer that can influence conclusions made on HER 2 status when
      analysing IHC equivocal samples in an effort to decrease the need for FISH
      testing. 113 patients in our records were included; charts were reviewed for
      different patient clinical characteristics and samples were analysed for
      pathological characteristics. RESULTS: Using logistic regression, progesterone
      receptor status and HER-2 staining of the normal glands around the tumour by IHC
      were the two statistically significant variables that showed association with
      FISH results. The strength of progesterone receptor status positivity and HER-2
      staining of the normal glands around the tumour were proportional to the
      likelihood of a negative FISH. Also, the presence of strong and diffuse hormone
      receptor positivity in low-grade tumours was predictive of negative HER-2 status.
      CONCLUSIONS: In countries where resources are strained, oncologists need to think
      of measures to minimise the increasing financial burden of cancer care. Our study
      serves to highlight a few clinicopathological characteristics that might
      eliminate the need for further testing through FISH.

PMID- 24108432
TI  - Four cases of solitary fibrous tumour of the eye and orbit: one with sarcomatous
      transformation after radiotherapy and one in a 5-year-old child's eyelid.
AB  - BACKGROUND: Solitary fibrous tumour (SFT) is quite a rare neoplasm involving the
      eye and the orbit. It is described as showing benign behaviour in adults, but
      malignant cases are exceptionally reported in this location. This report
      describes four new cases of SFT/giant cell angiofibroma (GCA) of the eyelid and
      orbit, one in a 5-year-old child, and one with sarcomatous dedifferentiated
      transformation occurring 9 years after radiotherapy. METHODS: Four cases of
      ocular SFT/GCA were retrieved from the database of the Pathological Anatomy Unit,
      University of Padova; immunohistochemistry and RT-PCR were used to identify
      COL1A1-PDBGF fusion gene transcripts in all cases. RESULTS: In case 1, late
      relapse 9 years later was characterised by abrupt transition into a high-grade
      component, associated with a non-distinctive high-grade sarcomatous area. The
      latter component was CD34, CD99 and Bcl2 negative and smooth muscle actin
      positive. Molecular characterisation showed the absence of COL1A1-PDGFB fusion
      transcripts in cases 1, 3 and 4, excluded diagnosis of giant cell fibroblastoma
      in all cases. Analysis could not be performed in case 2. CONCLUSIONS: An eyelid
      SFT/GCA in a 5-year-old child is the youngest case reported in the literature,
      indicating that the tumour is not exclusive to adults. The case with sarcomatous
      transformation, with dedifferentiated features occurring 9 years after
      radiotherapy, raises some questions about the choice of treatment for ocular SFT,
      in which excision is sometimes difficult without devastating surgery.

PMID- 24108433
TI  - Impact of the fracture risk assessment on patient and physician behavior in
      osteoporosis prevention.
AB  - OBJECTIVE: To evaluate the impact of a pharmacist-directed osteoporosis screening
      program utilizing the fracture risk assessment (FRAX) tool on patient and
      physician behavior. METHODS: Postmenopausal women 45 to 65 years with Achilles T
      score <-1.0 not receiving bisphosphonate therapy were randomly assigned to a
      control or intervention group. All participants received a heel ultrasound and
      pharmacist education on risks of low bone mass. The intervention group received
      the FRAX and shared their results with their physician. Three months after
      screening, a telephonic questionnaire was administered to all participants.
      RESULTS: A total of 749 patients were screened, with 87 meeting the enrollment
      criteria (43 control and 44 intervention). Physician behavior was not different
      between the groups with respect to ordering vitamin D levels, prescription
      medication, or dual-energy x-ray absorptiometry scan. A significant difference in
      vitamin D supplementation occurred between the 2 groups (P = .024). At follow-up,
      72.2% of responding participants increased daily calcium intake and 76.4% started
      or increased physical activity. CONCLUSION: Physician behavior was not influenced
      by FRAX results in the intervention group; however, positive patient behavior
      changes occurred in both groups. Primary prevention efforts conducted through
      heel ultrasound screening and pharmacist consultation led women to follow-up;
      however, awareness still needs to be raised of the value of FRAX in osteoporosis
      prevention.

PMID- 24108434
TI  - New phenolics from the flowers of Punica granatum and their in vitro alpha
      glucosidase inhibitory activities.
AB  - Two new phenolics, a 3-substituted coumarin, 7,8-dihydroxy-3
      carboxymethylcoumarin-5-carboxylic acid, and a hydrolyzable tannin, namely
      punicatannin C, together with 10 known phenolics, were isolated from the flowers
      of pomegranate (Punica granatum). Their structures were determined on the basis
      of extensive spectroscopic analyses including HRESIMS, 1D and 2D NMR data. All
      the isolates were evaluated for in vitro alpha-glucosidase inhibitory activities.

PMID- 24108435
TI  - Treatment of diabetes in the mouse model by delphinidin and cyanidin
      hydrochloride in free and liposomal forms.
AB  - Cyanidin and delphinidin are the main phenolic antioxidants in the grape (Vitis
      vinifera). The aim of this study was to investigate the in vitro and in vivo
      inhibitory effects of delphinidin and cyanidin chloride in the free and liposomal
      forms on the albumin glycation reaction. Delphinidin and cyanidin chlorides were
      encapsulated in the liposomes using an extrusion method. The rate of albumin
      glycation was evaluated using the ELISA method. Finally, in vivo anti-glycation
      of delphinidin and cyanidin chloride in the free and liposomal forms in diabetic
      mice was investigated. The encapsulation efficacies of delphinidin and cyanidin
      chloride in the liposomes were 89.05 % +/- 0.18 and 85.00 % +/- 0.15,
      respectively. In vitro treatment with 100 mg/mL delphinidin and cyanidin chloride
      in free forms could reduce the rate of albumin glycation to 30.50 +/- 3.46 and
      46.00 +/- 2.50 %, respectively. Under identical conditions, the delphinidin and
      cyanidin chloride-loaded liposomes could reduce the rate of albumin glycation to
      8.50 +/- 2.10 and 14.60 +/- 3.60 %, respectively. In vivo testing showed that
      anti-glycation activity of delphinidin and cyanidin in loaded forms was higher
      than in free forms. The daily administration of 100 mg/kg delphinidin chloride
      loaded liposomes to diabetic mice at eight weeks could decrease the rate of
      albumin and HbA1c glycation to 46.35 +/- 1.20 and 3.60 +/- 0.25 %, respectively.
      Moreover, under identical conditions, the loaded liposomes with cyanidin chloride
      could decrease the rate of albumin and HbA1c glycation to 55.56 +/- 1.32 and 4.95
      +/- 0.20 %, respectively. The findings showed that delphinidin and cyanidin
      chloride, in particular in the liposomal forms, could be used for treatment of
      diabetes mellitus complications. 

PMID- 24108436
TI  - Pharmacokinetics of isoliquiritigenin and its metabolites in rats: low
      bioavailability is primarily due to the hepatic and intestinal metabolism.
AB  - Isoliquiritigenin, a chalcone found in licorice has shown a variety of biological
      activities including antioxidative, anti-inflammatory, estrogenic,
      chemopreventive and antitumor effects. Thus, pharmacokinetics of
      isoliquiritigenin and its metabolites [liquiritigenin, glucuronidated
      isoliquiritigenin (M1), and glucuronidated liquiritigenin (M2)] after intravenous
      and oral administration of isoliquiritigenin was evaluated in rats. The
      pharmacokinetics of isoliquiritigenin, liquiritigenin, M1, and M2 showed no dose
      dependence after both intravenous and oral administration of isoliquiritigenin.
      Although approximately 92.0 % of the oral isoliquiritigenin was absorbed, the
      extent of the absolute bioavailability value was only 11.8 % of the oral dose.
      The low absolute bioavailability value of isoliquiritigenin might be due to the
      considerable metabolism of isoliquiritigenin in the small intestine and liver.
      This was supported by the facts that the ratios of AUC(M1)/AUC(isoLQ) and
      AUC(M2)/AUC(isoLQ) were high (over 0.25), isoliquiritigenin disappeared, and M1
      and M2 were formed mainly in S9 fractions of the liver and small intestine. The
      affinities of liquiritigenin, isoliquiritigenin, M1, and M2 were high in the
      liver, small intestine, large intestine, and/or kidney.

PMID- 24108437
TI  - Metabolism and excretion of kakkalide and its metabolites in rat urine, bile, and
      feces as determined by HPLC/UV and LC/MS/MS.
AB  - This study investigated the metabolic fate of kakkalide (irisolidone 7
      xylosylglucoside), a major isoflavone found in extracts of Pueraria lobata
      flowers, and in rat urine, bile, and feces. Using HPLC/UV or LC/MS/MS methods,
      seven metabolites, tectorigenin-7-O-glucuronide, tectorigenin-7-O-sulfate,
      tectorigenin-4'-O-sulfate, 6-OH biochanin A-glucuronide, irisolidone-7-O
      glucuronide, tectorigenin, and irisolidone were identified in rat urine after
      oral administration of kakkalide. Furthermore, irisolidone-7-O-glucuronide was
      found in bile, and irisolidone and kakkalide were found in feces. An HPLC/UV
      method for simultaneous quantification of all the metabolites and kakkalide in
      urine, bile, and feces was developed using daidzein or apigenin as the internal
      standard. Over a 72-h period, 13.2 +/- 2.8 % of the kakkalide was excreted as
      seven metabolites in urine. Over the same time period, irisolidone-7-O
      glucuronide excretion in bile accounted for 3.8 +/- 1.1 % of the dose, while
      kakkalide and irisolidone excretion in feces accounted for 2.1 +/- 0.7 % and 0.7
      +/- 0.1 % of the dose, respectively. The results indicate that urine is the
      primary route of kakkalide elimination in vivo and that extensive metabolism may
      be one of the reasons for the low bioavailability of kakkalide. 

PMID- 24108438
TI  - Is there a role for beta-blockade in septic shock?

PMID- 24108439
TI  - Elevated fatty acid synthase expression in prostate needle biopsy cores predicts
      upgraded Gleason score in radical prostatectomy specimens.
AB  - BACKGROUND: We examined whether fatty acid synthase (FAS) expression in prostate
      biopsy cores had valuable information and could predict a Gleason score (GS)
      upgraded from biopsy to radical prostatectomy (RP) specimens. METHODS:
      Immunostaining with a FAS antibody was performed on paraffin-embedded prostate
      biopsy cores with GS 5-6 obtained from 80 patients who subsequently underwent RP.
      The correlations between FAS expression and clinicopathological parameters,
      upgrading group, and clinicopathological parameters including FAS expression were
      analyzed. Logistic regression analysis was performed to identify a significant
      set of independent predictors for upgrading GS. RESULTS: A total of 46 patients
      (57.5%) with biopsy GS 5-6 were upgraded to GS >=7 at RP. FAS expression was
      significantly associated with clinical T stage (P = 0.0232) and positive core
      rate (P = 0.0245). Upgrading from biopsy GS 5-6 to GS >=7 at RP was significantly
      associated with clinical T stage (P = 0.0337), positive core rate (P = 0.0262),
      and FAS expression (P < 0.0001). FAS expression was a significant predictor for
      upgrading from biopsy GS 5-6 to GS >=7 at RP in multivariate analysis (P <
      0.0001; odds ratio, 12.35). FAS scores showed the largest area under the receiver
      operating characteristic curve (AUC) in preoperative parameters (AUC = 0.753).
      CONCLUSIONS: Increased FAS expression in prostate biopsy cores could be a novel
      parameter for upgrading from biopsy GS 5-6 to GS >=7 at RP. If a biopsy GS is
      low, the treatment strategy for patients with high FAS expression in prostate
      biopsy cores should be carefully determined.

PMID- 24108440
TI  - Increased hippocampal glutamate and volumetric deficits in unmedicated patients
      with schizophrenia.
AB  - IMPORTANCE: Alterations in glutamatergic neurotransmission have been postulated
      to be a key pathophysiologic mechanism in schizophrenia. OBJECTIVE: To evaluate
      hippocampal volumetric measures and neurometabolites in unmedicated patients with
      schizophrenia and the correlations between these markers. Our a priori hypothesis
      was that glutamate levels would negatively correlate with hippocampal volume in
      schizophrenia. DESIGN, SETTING, AND PARTICIPANTS: Combined 3-T structural
      magnetic resonance imaging and single-voxel proton magnetic resonance
      spectroscopy study at the Department of Psychiatry and Behavioral Neurobiology,
      University of Alabama at Birmingham, of 27 unmedicated patients with
      schizophrenia and 27 healthy controls. MAIN OUTCOMES AND MEASURES: Hippocampal
      volumetric measures and neurometabolites, and the correlations between volumetric
      measurements and neurometabolites. RESULTS: Hippocampal volumetric deficits,
      increased ratios of hippocampal glutamate and glutamine to creatine (Glx/Cr), and
      a loss of correlation between hippocampal N-acetylaspartate (NAA)/Cr and Glx/Cr
      in patients with schizophrenia were found. Significant correlations between
      hippocampal volumetric measures and Glx/Cr were also found in patients with
      schizophrenia but not healthy controls. CONCLUSIONS AND RELEVANCE: Our findings
      support the theory that alterations in hippocampal glutamate levels potentially
      account for structural deficits in the hippocampus observed in schizophrenia
      neuroimaging studies.

PMID- 24108441
TI  - Bioluminescence as a light source for photosynthesis.
AB  - The luminol bioluminescence system containing luminol, hydrogen peroxide and HRP
      was used as a potential substitute light source of sunlight for the
      photosynthesis of plants, in which the electron flow of the photosynthesis
      process was proven using chloroplasts isolated from spinach leaves. 

PMID- 24108442
TI  - Discovery of a new class of immunosuppressants from Trichothecium roseum co
      inspired by cross-kingdom similarity in innate immunity and pharmacophore motif.
AB  - The limited selection of immunosuppressants in the clinic hampers the efficient
      management of immune disorders such as rejections after organ transplantations.
      However, the search for new immunosuppressive compounds remains random and
      creates inevitably financial and laborious wastes. Herein, we present an immunity
      inspired discovery strategy that rationally allows an efficient identification of
      immunosuppressive compounds from the endophyte culture, as exemplified by the new
      peptide trichomide A. This compound exerts its immunosuppressive action more
      selectively than cyclosporin A. It was found that trichomide A decreases the
      expression of Bcl-2, increases the expression of Bax, and has a small or
      negligible effect on the expressions of p-Akt, CD25, and CD69. Our study
      strengthens the idea that the cross-kingdom similarity in immunity among living
      things could provide a shorter route towards the identification of natural
      products valuable for the development of new immunosuppressants. 

PMID- 24108443
TI  - Nickel-catalyzed arylation, alkenylation, and alkynylation of unprotected
      thioglycosides at room temperature.
AB  - Unprotected thioglycosides were effective nucleophiles for Ni(0)-catalyzed C-S
      bond-forming reaction with functionalized (hetero)aryl, alkenyl, and alkynyl
      halides. The functional-group tolerance on the electrophilic partner was
      typically high and the anomeric selectivities of the thioglycosides were high in
      all cases. The efficiency of this general procedure was well-demonstrated by the
      synthesis of 4-methyl-7-thioumbelliferyl-beta-D-cellobioside (MUS-CB).

PMID- 24108444
TI  - Tracking stem cells in tissue-engineered organs using magnetic nanoparticles.
AB  - The use of human stem cells (SCs) in tissue engineering holds promise in
      revolutionising the treatment of numerous diseases. There is a pressing need to
      comprehend the distribution, movement and role of SCs once implanted onto
      scaffolds. Nanotechnology has provided a platform to investigate this through the
      development of inorganic magnetic nanoparticles (MNPs). MNPs can be used to label
      and track SCs by magnetic resonance imaging (MRI) since this clinically available
      imaging modality has high spatial resolution. In this review, we highlight recent
      applications of iron oxide and gadolinium based MNPs in SC labelling and MRI; and
      offer novel considerations for their future development. 

PMID- 24108445
TI  - T-cell help dependence of memory CD8+ T-cell expansion upon vaccinia virus
      challenge relies on CD40 signaling.
AB  - Due to their capacity to differentiate into long-lived memory cells, CD8(+) T
      cells are able to resolve subsequent infections faster than during the primary
      response. Among other factors, CD4(+) T cells play a crucial role during primary
      and secondary CD8(+) T-cell responses. However, the timing and mechanisms by
      which they influence CD8(+) T cells may differ in primary and secondary
      responses. Here, we demonstrate that during both primary and secondary vaccinia
      virus infection, CD4(+) T cells are necessary to promote CD8(+) T-cell responses.
      While CD4(+) T cells contributed to memory CD8(+) T-cell development, they were
      even more important during memory recall responses during challenge, as absence
      of CD4(+) T cells during challenge resulted in markedly decreased proliferation
      and increased apoptosis. T-cell help during primary and secondary responses was
      mediated via CD40 signaling, with DCs being an integral part of that pathway. As
      opposed to primary CD8(+) T-cell responses where only a combination of agonistic
      CD40 signaling and provision of IL-2 could substitute for T-cell help, agonistic
      CD40 triggering alone was sufficient to rescue memory CD8(+) T-cell responses in
      absence of T-cell help in the context of vaccinia virus infection. 

PMID- 24108446
TI  - Topical analgesics for neuropathic pain: preclinical exploration, clinical
      validation, future development.
AB  - Topical analgesics applied locally to skin or to specialized compartments modify
      pain by actions on sensory nerve endings and/or adjacent cellular elements. With
      this approach, there are low systemic drug levels, good tolerability and few drug
      interactions, and combination with oral formulations is feasible. The goal of
      this review is to provide an overview of the potential for topical analgesics to
      contribute to improved management of neuropathic pain. Mechanistic and
      preclinical studies indicate much potential for development of novel topical
      analgesics for neuropathic pain. In humans, two topical analgesics are approved
      for use in post-herpetic neuralgia (lidocaine 5% medicated plaster, capsaicin 8%
      patch), and there is evidence for efficacy in other neuropathic pain conditions.
      Comparative trials indicate similar efficacy between topical and oral analgesics.
      Not all individuals respond to topical analgesics, and there is interest in
      determining factors (patient factors, sensory characteristics) which might
      predict responsiveness to topical analgesics. There is a growing number of
      controlled trials and case reports of investigational agents (vasodilators,
      glutamate receptor antagonists, alpha2-adrenoreceptor agonists, antidepressants,
      centrally acting drugs), including combinations of several agents, indicating
      these produce pain relief in neuropathic pain. There is interest in compounding
      topical analgesics for neuropathic pain, but several challenges remain for this
      approach. Topical analgesics have the potential to be a valuable additional
      approach for the management of neuropathic pain. 

PMID- 24108447
TI  - The endophenotype and the phenotype: temporal discrimination and adult-onset
      dystonia.
AB  - The pathogenesis and the genetic basis of adult-onset primary torsion dystonia
      remain poorly understood. Because of markedly reduced penetrance in this
      disorder, a number of endophenotypes have been proposed; many of these may be
      epiphenomena secondary to disease manifestation. Mediational endophenotypes
      represent gene expression; the study of trait (endophenotypic) rather than state
      (phenotypic) characteristics avoids the misattribution of secondary adaptive
      cerebral changes to pathogenesis. We argue that abnormal temporal discrimination
      is a mediational endophenotype; its use facilitates examination of the effects of
      age, gender, and environment on disease penetrance in adult-onset dystonia. Using
      abnormal temporal discrimination in unaffected first-degree relatives as a marker
      for gene mutation carriage may inform exome sequencing techniques in families
      with few affected individuals. We further hypothesize that abnormal temporal
      discrimination reflects dysfunction in an evolutionarily conserved subcortical
      basal ganglia circuit for the detection of salient novel environmental change.
      The mechanisms of dysfunction in this pathway should be a focus for future
      research in the pathogenesis of adult-onset primary torsion dystonia.

PMID- 24108448
TI  - Automated determination of metastases in unstructured radiology reports for
      eligibility screening in oncology clinical trials.
AB  - Enrolling adequate numbers of patients that meet protocol eligibility criteria in
      a timely manner is critical, yet clinical trial accrual continues to be
      problematic. One approach to meet these accrual challenges is to utilize
      technology to automatically screen patients for clinical trial eligibility. This
      manuscript reports on the evaluation of different automated approaches to
      determine the metastatic status from unstructured radiology reports using the
      Clinical Trials Eligibility Database Integrated System (CTED). The study sample
      included all patients (N = 5,523) with radiologic diagnostic studies (N = 10,492)
      completed in a two-week period. Eight search algorithms (queries) within CTED
      were developed and applied to radiology reports. The performance of each
      algorithm was compared to a reference standard which consisted of a physician's
      review of the radiology reports. Sensitivity, specificity, positive, and negative
      predicted values were calculated for each algorithm. The number of patients
      identified by each algorithm varied from 187 to 330 and the number of true
      positive cases confirmed by physician review ranged from 171 to 199 across the
      algorithms. The best performing algorithm had sensitivity 94%, specificity 100%,
      positive predictive value 90%, negative predictive value 100%, and accuracy of
      99%. Our evaluation process identified the optimal method for rapid
      identification of patients with metastatic disease through automated screening of
      unstructured radiology reports. The methods developed using the CTED system could
      be readily implemented at other institutions to enhance the efficiency of
      research staff in the clinical trials eligibility screening process. 

PMID- 24108449
TI  - Luminescent gold nanoparticles: a new class of nanoprobes for biomedical imaging.
AB  - Our fundamental understanding of cell biology and early diagnosis of human
      diseases have been greatly benefited from the development of fluorescent probes.
      Over the past decade, luminescent gold nanoparticles (AuNPs) with diverse
      structural parameters including particle size, surface ligands, valence state and
      grain size have been synthesized and have begun to emerge as a new class of
      fluorescent probes for bioimaging because of their great biocompatibility, robust
      photophysical properties and tunable emissions from the visible range to the near
      infrared region. In this minireview, we summarize the recent progress in
      applications of different-sized luminescent AuNPs as imaging probes for both in
      vitro and in vivo levels. 

PMID- 24108450
TI  - Toxoplasma encephalitis in an HIV-infected patient on highly active
      antiretroviral therapy despite sustained immune response.
AB  - Toxoplasma encephalitis (TE) is usually diagnosed in advanced stages of HIV
      infection when the CD4+ count is <100-200 cells/ul. A 55-year-old woman with
      HIV/AIDS, well controlled on antiretroviral therapy (ART), CD4+ count in the 300
      cells/MUl range for >1 year presented with acute onset of headache, nausea and
      vomiting. She had been on her current ART regimen consisting of raltegravir, co
      formulated emtricitabine/tenofovir and etravirine for three years and had been
      off Pneumocystis prophylaxis for 10 months (trimethoprim-sulfamethoxazole). Brain
      MRI showed multiple ring-enhancing, supratentorial and infra-tentorial
      parenchymal lesions suspicious for metastases. She had no other evidence of
      metastatic disease in her body. The possibilities of TE and primary CNS lymphoma
      were considered but deemed unlikely given the high CD4+ count. A brain biopsy
      demonstrated Toxoplasma tachyzoites. There was no evidence of lymphoma or
      carcinoma. Anti-toxoplasma treatment yielded good initial clinical and
      radiographic responses. While on TE maintenance therapy, she developed similar
      symptoms. Repeat MRI showed progression of lesions. Further work-up including CSF
      Epstein-Barr virus PCR and SPECT Th 201 imaging was not conclusive for CNS
      lymphoma. The patient's clinical condition deteriorated and she died. We
      postulate that functional immunological dysfunction is a possible mechanism by
      which our patient developed TE despite demonstrating sustained immune response on
      ART.

PMID- 24108451
TI  - Bringing testing to the people - benefits of mobile unit HIV/syphilis testing in
      Lima, Peru, 2007-2009.
AB  - Mobile unit (MU) HIV testing is an alternative method of providing healthcare
      access. We compared demographic and behavioural characteristics, HIV testing
      history and HIV prevalence between participants seeking testing at a MU vs. fixed
      clinic (FC) in Lima, Peru. Our analysis included men and transgender women (TW)
      in Lima aged >= 18 years old seeking HIV testing at their first visit to a
      community-based MU or FC from October 2007 to November 2009. HIV testing history,
      HIV serostatus and behavioural characteristics were analysed. A large percentage
      of MU attendees self-identified as transgender (13%) or heterosexual (41%). MU
      attendees were more likely to engage in transactional sex (24% MU vs. 10% FC, p <
      0.001), use alcohol/drugs during their last sexual encounter (24% MU vs. 20% FC,
      p < 0.01) and/or be a first-time HIV tester (48% MU vs. 41% FC, p < 0.001). MU
      HIV prevalence was 9% overall and 5% among first-time testers (49% in TW and 11%
      in men who have sex with men [MSM] first-time testers). MU testing reached large
      numbers of at-risk (MSM/TW) populations engaged in unsafe sexual behaviours,
      making MU outreach a worthy complement to FC testing. Investigation into whether
      MU attendees would otherwise access HIV testing is warranted to determine the
      impact of MU testing.

PMID- 24108452
TI  - Atazanavir and chest pain.
AB  - We present a case of a 41-year-old man complaining of chest pain, which he
      directly attributed to his antiretrovirals, specifically atazanavir and
      ritonavir. The chest pain resolved on stopping the treatment, and recurred when
      atazanavir was restarted, again resolving on discontinuation. Cardiovascular risk
      factors are an important consideration with any antiretroviral therapy but
      particularly with protease inhibitors. The association between atazanavir and
      cardiac arrhythmias has been reported elsewhere including the British National
      Formulary, and it may be good practice to perform electrocardiogram assessments
      in patients commencing and using atazanavir-based regimens. 

PMID- 24108453
TI  - Symptomatic relapse of HIV-associated cryptococcal meningitis: recurrent
      cryptococcal meningitis or Cryptococcus-related immune reconstitution
      inflammatory syndrome?
AB  - Cryptococcosis, a significant opportunistic infection, has become a global
      concern since the advent of immunosuppressive chemotherapy or in immunodeficient
      patients. Host responses range from a harmless colonization to disseminated
      disease. An accurate or definitive diagnosis in patients with cryptococcal
      meningitis is often delayed because of the similar clinical presentation and
      biochemical or cerebrospinal fluid findings to those of a variety of infectious
      and non-infectious aetiologies, most of which are also especially prevalent in
      developing countries. Rarely, patients with cryptococcal meningitis can develop
      immune reconstitution inflammatory syndrome (IRIS) when initiated on combination
      antiretroviral therapy (cART) the diagnosis which is often missed and can be
      fatal. Due to the similar presentation of infection and IRIS, it is often
      confused with the relapse of cryptococcal meningitis. We report a case of
      paradoxical recurrent meningitis in response to the initiation of cART in a
      patient diagnosed with cryptococcal meningitis and propose that the recurrent
      symptoms resulted from a therapy-induced reconstitution of the immune response
      against residual Cryptococcus neoformans.

PMID- 24108454
TI  - Biopsy using a magnetic capsule endoscope carrying, releasing, and retrieving
      untethered microgrippers.
AB  - This paper proposes a new wireless biopsy method where a magnetically actuated
      untethered soft capsule endoscope carries and releases a large number of thermo
      sensitive, untethered microgrippers (MU-grippers) at a desired location inside
      the stomach and retrieves them after they self-fold and grab tissue samples. We
      describe the working principles and analytical models for the MU-gripper release
      and retrieval mechanisms, and evaluate the proposed biopsy method in ex vivo
      experiments. This hierarchical approach combining the advanced navigation skills
      of centimeter-scaled untethered magnetic capsule endoscopes with highly parallel,
      autonomous, submillimeter scale tissue sampling MU-grippers offers a
      multifunctional strategy for gastrointestinal capsule biopsy.

PMID- 24108455
TI  - A submillimetric 3-DOF force sensing instrument with integrated fiber Bragg
      grating for retinal microsurgery.
AB  - Vitreoretinal surgery requires very fine motor control to perform precise
      manipulation of the delicate tissue in the interior of the eye. Besides
      physiological hand tremor, fatigue, poor kinesthetic feedback, and patient
      movement, the absence of force sensing is one of the main technical challenges.
      Previous two degrees of freedom (DOF) force sensing instruments have demonstrated
      robust force measuring performance. The main design challenge is to incorporate
      high sensitivity axial force sensing. This paper reports the development of a
      submillimetric 3-DOF force sensing pick instrument based on fiber Bragg grating
      (FBG) sensors. The configuration of the four FBG sensors is arranged to maximize
      the decoupling between axial and transverse force sensing. A superelastic nitinol
      flexure is designed to achieve high axial force sensitivity. An automated
      calibration system was developed for repeatability testing, calibration, and
      validation. Experimental results demonstrate a FBG sensor repeatability of 1.3
      pm. The linear model for calculating the transverse forces provides an accurate
      global estimate. While the linear model for axial force is only locally accurate
      within a conical region with a 30 degrees  vertex angle, a second-order
      polynomial model can provide a useful global estimate for axial force. Combining
      the linear model for transverse forces and nonlinear model for axial force, the 3
      DOF force sensing instrument can provide sub-millinewton resolution for axial
      force and a quarter millinewton for transverse forces. Validation with random
      samples show the force sensor can provide consistent and accurate measurement of
      3-D forces.

PMID- 24108457
TI  - Minimum variance brain source localization for short data sequences.
AB  - In the electroencephalogram (EEG) or magnetoencephalogram (MEG) context, brain
      source localization methods that rely on estimating second-order statistics often
      fail when the number of samples of the recorded data sequences is small in
      comparison to the number of electrodes. This condition is particularly relevant
      when measuring evoked potentials. Due to the correlated background EEG/MEG
      signal, an adaptive approach to localization is desirable. Previous work has
      addressed these issues by reducing the adaptive degrees of freedom (DoFs). This
      reduction results in decreased resolution and accuracy of the estimated source
      configuration. This paper develops and tests a new multistage adaptive processing
      technique based on the minimum variance beamformer for brain source localization
      that has been previously used in the radar statistical signal processing context.
      This processing, referred to as the fast fully adaptive (FFA) approach, can
      significantly reduce the required sample support, while still preserving all
      available DoFs. To demonstrate the performance of the FFA approach in the limited
      data scenario, simulation and experimental results are compared with two previous
      beamforming approaches; i.e., the fully adaptive minimum variance beamforming
      method and the beamspace beamforming method. Both simulation and experimental
      results demonstrate that the FFA method can localize all types of brain activity
      more accurately than the other approaches with limited data.

PMID- 24108456
TI  - Small-animal whole-body photoacoustic tomography: a review.
AB  - With the wide use of small animals for biomedical studies, in vivo small-animal
      whole-body imaging plays an increasingly important role. Photoacoustic tomography
      (PAT) is an emerging whole-body imaging modality that shows great potential for
      preclinical research. As a hybrid technique, PAT is based on the acoustic
      detection of optical absorption from either endogenous tissue chromophores, such
      as oxyhemoglobin and deoxyhemoglobin, or exogenous contrast agents. Because
      ultrasound scatters much less than light in tissue, PAT generates high-resolution
      images in both the optical ballistic and diffusive regimes. Using near-infrared
      light, which has relatively low blood absorption, PAT can image through the whole
      body of small animals with acoustically defined spatial resolution. Anatomical
      and vascular structures are imaged with endogenous hemoglobin contrast, while
      functional and molecular images are enabled by the wide choice of exogenous
      optical contrasts. This paper reviews the rapidly growing field of small-animal
      whole-body PAT and highlights studies done in the past decade. 

PMID- 24108459
TI  - Muscle injury during critical illness.

PMID- 24108458
TI  - Detection and quantification of focal uptake in head and neck tumours: (18)F-FDG
      PET/MR versus PET/CT.
AB  - PURPOSE: Our objectives were to assess the quality of PET images and coregistered
      anatomic images obtained with PET/MR, to evaluate the detection of focal uptake
      and SUV, and to compare these findings with those of PET/CT in patients with head
      and neck tumours. METHODS: The study group comprised 32 consecutive patients with
      malignant head and neck tumours who underwent whole-body (18)F-FDG PET/MR and
      PET/CT. PET images were reconstructed using the attenuation correction sequence
      for PET/MR and CT for PET/CT. Two experienced observers evaluated the anonymized
      data. They evaluated image and fusion quality, lesion conspicuity, anatomic
      location, number and size of categorized (benign versus assumed malignant)
      lesions with focal uptake. Region of interest (ROI) analysis was performed to
      determine SUVs of lesions and organs for both modalities. Statistical analysis
      considered data clustering due to multiple lesions per patient. RESULTS: PET/MR
      coregistration and image fusion was feasible in all patients. The analysis
      included 66 malignant lesions (tumours, metastatic lymph nodes and distant
      metastases), 136 benign lesions and 470 organ ROIs. There was no statistically
      significant difference between PET/MR and PET/CT regarding rating scores for
      image quality, fusion quality, lesion conspicuity or anatomic location, number of
      detected lesions and number of patients with and without malignant lesions. A
      high correlation was observed for SUVmean and SUVmax measured on PET/MR and
      PET/CT for malignant lesions, benign lesions and organs (rho = 0.787 to 0.877, p
      < 0.001). SUVmean and SUVmax measured on PET/MR were significantly lower than on
      PET/CT for malignant tumours, metastatic neck nodes, benign lesions, bone marrow,
      and liver (p < 0.05). The main factor affecting the difference between SUVs in
      malignant lesions was tumour size (p < 0.01). CONCLUSION: In patients with head
      and neck tumours, PET/MR showed equivalent performance to PET/CT in terms of
      qualitative results. Comparison of SUVs revealed an excellent correlation for
      measurements on both modalities, but underestimation of SUVs measured on PET/MR
      as compared to PET/CT.

PMID- 24108460
TI  - How I treat monoclonal gammopathy of renal significance (MGRS).
AB  - Recently, the term monoclonal gammopathy of renal significance (MGRS) was
      introduced to distinguish monoclonal gammopathies that result in the development
      of kidney disease from those that are benign. By definition, patients with MGRS
      have B-cell clones that do not meet the definition of multiple myeloma or
      lymphoma. Nevertheless, these clones produce monoclonal proteins that are capable
      of injuring the kidney resulting in permanent damage. Except for immunoglobulin
      light chain amyloidosis with heart involvement in which death can be rapid,
      treatment of MGRS is often indicated more to preserve kidney function and prevent
      recurrence after kidney transplantation rather than the prolongation of life.
      Clinical trials are rare for MGRS-related kidney diseases, except in
      immunoglobulin light chain amyloidosis. Treatment recommendations are therefore
      based on the clinical data obtained from treatment of the clonal disorder in its
      malignant state. The establishment of these treatment recommendations is
      important until data can be obtained by clinical trials of MGRS-related kidney
      diseases. 

PMID- 24108463
TI  - Fast tomographic reconstruction from limited data using artificial neural
      networks.
AB  - Image reconstruction from a small number of projections is a challenging problem
      in tomography. Advanced algorithms that incorporate prior knowledge can sometimes
      produce accurate reconstructions, but they typically require long computation
      times. Furthermore, the required prior knowledge can be very specific, limiting
      the type of images that can be reconstructed. Here, we present a reconstruction
      method that automatically learns prior knowledge using an artificial neural
      network. We show that this method can be viewed as a combination of filtered
      backprojection steps, and, therefore, has a relatively low computational cost.
      Results for two different cases show that the new method is able to use the
      learned information to produce high quality reconstructions in a short time, even
      when presented with a small number of projections.

PMID- 24108462
TI  - Unraveling a novel transcription factor code determining the human arterial
      specific endothelial cell signature.
AB  - Endothelial cells (ECs) lining arteries and veins have distinct
      molecular/functional signatures. The underlying regulatory mechanisms are
      incompletely understood. Here, we established a specific fingerprint of freshly
      isolated arterial and venous ECs from human umbilical cord comprising 64 arterial
      and 12 venous genes, representing distinct functions/pathways. Among the arterial
      genes were 8 transcription factors (TFs), including Notch target HEY2, the
      current "gold standard" determinant for arterial EC (aEC) specification. Culture
      abrogated differential gene expression in part due to gradual loss of canonical
      Notch activity and HEY2 expression. Notably, restoring HEY2 expression or Delta
      like4-induced Notch signaling in cultured ECs only partially reinstated the aEC
      gene signature, whereas combined overexpression of the 8 TFs restored this
      fingerprint more robustly. Whereas some TFs stimulated few genes, others boosted
      a large proportion of arterial genes. Although there was some overlap and cross
      regulation, the TFs largely complemented each other in regulating the aEC gene
      profile. Finally, overexpression of the 8 TFs in human umbilical vein ECs
      conveyed an arterial-like behavior upon their implantation in a Matrigel plug in
      vivo. Thus, our study shows that Notch signaling determines only part of the aEC
      signature and identifies additional novel and complementary transcriptional
      players in the complex regulation of human arteriovenous EC identity.

PMID- 24108461
TI  - A critical role for Lyn kinase in strengthening endothelial integrity and barrier
      function.
AB  - The Src family kinases (SFKs) c-Src and Yes mediate vascular leakage in response
      to various stimuli including lipopolysaccharide (LPS) and vascular endothelial
      growth factor (VEGF). Here, we define an opposing function of another SFK, Lyn,
      which in contrast to other SFKs, strengthens endothelial junctions and thereby
      restrains the increase in vascular permeability. Mice lacking Lyn displayed
      increased mortality in LPS-induced endotoxemia and increased vascular
      permeability in response to LPS or VEGF challenge compared with wild-type
      littermates. Lyn knockout mice repopulated with wild-type bone marrow-derived
      cells have higher vascular permeability than wild-type mice, suggesting a role of
      endothelial Lyn in the maintenance of the vascular barrier. Small interfering RNA
      mediated down-regulation of Lyn disrupted endothelial barrier integrity, whereas
      expression of a constitutively active mutant of Lyn enhanced the barrier.
      However, down-regulation of Lyn did not affect LPS-induced endothelial
      permeability. We demonstrate that Lyn association with focal adhesion kinase
      (FAK) and phosphorylation of FAK at tyrosine residues 576/577 and 925 were
      required for Lyn-dependent stabilization of endothelial adherens junctions. Thus,
      in contrast to c-Src and Yes, which increase vascular permeability in response to
      stimuli, Lyn stabilizes endothelial junctions through phosphorylation of FAK.
      Therefore, therapeutics activating Lyn kinase may strengthen the endothelial
      barrier junction and hence have anti-inflammatory potential. 

PMID- 24108464
TI  - Metamer mismatching.
AB  - A new algorithm for calculating the metamer mismatch volumes that arise in colour
      vision and colour imaging is introduced. Unlike previous methods, the proposed
      method places no restrictions on the set of possible object reflectance spectra.
      As a result of such restrictions, previous methods have only been able to provide
      approximate solutions to the mismatch volume. The proposed new method is the
      first to characterize precisely the metamer mismatch volume for any possible
      reflectance. 

PMID- 24108465
TI  - Single-image noise level estimation for blind denoising.
AB  - Noise level is an important parameter to many image processing applications. For
      example, the performance of an image denoising algorithm can be much degraded due
      to the poor noise level estimation. Most existing denoising algorithms simply
      assume the noise level is known that largely prevents them from practical use.
      Moreover, even with the given true noise level, these denoising algorithms still
      cannot achieve the best performance, especially for scenes with rich texture. In
      this paper, we propose a patch-based noise level estimation algorithm and suggest
      that the noise level parameter should be tuned according to the scene complexity.
      Our approach includes the process of selecting low-rank patches without high
      frequency components from a single noisy image. The selection is based on the
      gradients of the patches and their statistics. Then, the noise level is estimated
      from the selected patches using principal component analysis. Because the true
      noise level does not always provide the best performance for nonblind denoising
      algorithms, we further tune the noise level parameter for nonblind denoising.
      Experiments demonstrate that both the accuracy and stability are superior to the
      state of the art noise level estimation algorithm for various scenes and noise
      levels.

PMID- 24108466
TI  - Hybrid patching for a sequence of differently exposed images with moving objects.
AB  - It is very challenging to synthesize a high dynamic range (HDR) image from
      multiple differently exposed low dynamic range images when there are moving
      objects in the images. This is due to the fact that the moving objects will cause
      ghosting artifacts to appear in the synthesized HDR image. To prevent such
      artifacts, a patching algorithm is required to correct motion regions such that
      all the moving objects are synchronized in the differently exposed images. In
      this paper, a new optimization problem is formulated to correct the motion
      regions of the multiple differently exposed images by considering both spatial
      and temporal consistencies. The resultant scheme is a hybrid patching scheme
      composed of a correction method which is an intensity mapping function at pixel
      level, and a hole-filling method that uses block-level template matching. The
      proposed patching scheme is not only robust to large intensity changes in these
      input images, but also at regions that are over- or underexposed. Experimental
      results show that the proposed method is able to prevent ghosting artifacts from
      appearing in the final synthesized HDR image.

PMID- 24108467
TI  - Identification of a novel complex BRAF mutation associated with major clinical
      response to vemurafenib in a patient with metastatic melanoma.
AB  - IMPORTANCE: There is an increasing interest in BRAF V600 mutations in melanomas
      and their associated sensitivity to vemurafenib, a BRAF inhibitor. However,
      physicians cannot find information in the literature about vemurafenib response
      for rare and/or atypical BRAF mutations. OBSERVATIONS: We describe the
      identification of a novel complex BRAF mutation associated with major clinical
      response to vemurafenib in a patient with metastatic melanoma. Using a
      pyrosequencing method, we determined that the tumor positive for mutated BRAF,
      uncovering a novel c.1799_1803delinsAT; p.V600-K601>D variant. We uncovered this
      atypical BRAF mutation with 2 different sequencing methods, both in the primary
      lesion and in 1 metastasis. The patient was immediately treated with vemurafenib
      as monotherapy and achieved a prolonged (5.5-month) positive response.
      CONCLUSIONS AND RELEVANCE: We analyzed the consequences of the BRAF V600-K601>D
      mutation in terms of amino acids. We referred to the published data and databases
      to screen chemical properties of well-known BRAF V600 mutations and other complex
      BRAF mutations to find common features of activated BRAF mutations. Importantly,
      we highlighted that both the site of the mutation and the involved amino acids
      are important to predict vemurafenib response. Our conclusion is that complex
      BRAF mutation surrounding codon 600 could also be sensitive to BRAF inhibitors.

PMID- 24108468
TI  - Coagulation in inflammatory diseases of the central nervous system.
AB  - Thrombin and other proteases involved in coagulation also have the potential to
      stimulate inflammation in the brain to a large extent through the protease
      activated receptors (PARs). Such exposure of the brain to increased levels of
      coagulation factors is more likely to occur during vasculitis and activation of
      intrinsic coagulation in the brain and may cause inflammatory diseases such as
      multiple sclerosis. There is growing evidence from animal models and human brain
      samples that links upregulation of coagulation factors to inflammatory central
      nervous system (CNS) disease. Evidence includes measures of thrombin-like
      activity, levels of its receptors, PARs, and inhibitors of the coagulation
      pathway. The major receptor for thrombin, PAR-1, has now been definitively
      located to the synapse and node of Ranvier and its excessive activation leads to
      blocks in long-term potentiation and in nerve conduction. There is growing
      evidence that modulating coagulation in models of CNS inflammatory disease has
      beneficial clinical effects. These findings suggest that coagulation-like
      pathways play a significant role in the pathogenesis of inflammatory diseases in
      the CNS and present a viable target for therapeutic strategies. 

PMID- 24108469
TI  - Vitamin K and brain function.
AB  - One of the fat-soluble vitamins, vitamin K was initially discovered for its role
      in blood coagulation. Although several vitamin K-dependent hemostatic proteins
      are particularly important for the brain, other vitamin K-dependent proteins
      (VKDPs), not associated with blood coagulation, also contribute to the brain
      function. In addition to the VKDPs, vitamin K participates in the nervous system
      through its involvement in sphingolipid metabolism, a class of lipids widely
      present in brain cell membranes. Classically known for their structural role,
      sphingolipids are biologically potent molecules involved in a wide range of
      cellular actions. Also, there is growing evidence that the K vitamer, menaquinone
      4, has anti-inflammatory activity and offers protection against oxidative stress.
      Finally, although limited in numbers, reports point to a modulatory role of
      vitamin K in cognition. This short review presents an overview of the known role
      of vitamin K in brain function to date. 

PMID- 24108470
TI  - Multiple roles of tissue plasminogen activator in schizophrenia pathophysiology.
AB  - Schizophrenia, a disabling mental disorder, is characterized by brain atrophy,
      especially in the superior temporal gyrus and the medial temporal lobe, which
      includes the hippocampus and the amygdala. The model that better explains brain
      atrophy includes a trigger and a predisposing condition. The trigger is
      exemplified by illicit drugs or environmental stressors that promote release of
      substances harmful to the neurons, such as glucocorticoids or noradrenalin.
      Predisposed patients would have one or more conditions that impair neuronal
      plasticity and neurogenesis. Evidence indicates that abnormal tissue plasminogen
      activator (tPA) activity is an important predisposing condition. tPA plays an
      important role in synaptic regulation and plasticity, and in neurogenesis, being
      crucial to the biology of memory, learning, and emotions. Several biochemical
      abnormalities seen in schizophrenics are related to decreased levels or impaired
      activity of tPA, including deficient dopamine transmission at D1 receptors in the
      prefrontal cortex, impaired cleavage of a precursor of brain-derived neurotrophic
      factor into its mature form (mature brain-derived neurotrophic factor), abnormal
      N-methyl-d-aspartate receptor-mediated signaling, reduced Akt phosphorylation,
      and abnormal activation of reelin. Clinical conditions related to schizophrenia,
      such as hyperhomocysteinemia, insulin resistance, and type 2 diabetes mellitus
      are characterized by a loss of tPA function or decreased tPA levels. This article
      reviews how low levels or abnormal function of tPA are related to the
      pathogenesis of schizophrenia. 

PMID- 24108471
TI  - Brain neoplasms and coagulation.
AB  - Brain vasculature is uniquely programmed to protect central nervous system
      tissues and respond to their metabolic demands. These functions are subverted
      during the development of primary and metastatic brain tumors, resulting in
      vascular perturbations that are thought to contribute to progression and
      comorbidities of the underlying disease, including thrombosis and hemorrhage.
      Chronic activation of the coagulation system is particularly obvious in
      glioblastoma multiforme (GBM), where intratumoral vasoocclusive thrombosis may
      contribute to hypoxia, pseudopalisading necrosis, and angiogenesis. GBM is also
      associated with spontaneous or iatrogenic bleeding, and the emission of
      circulating procoagulants implicated in the unusually high risk of peripheral
      venous thromboembolism. Tissue factor (TF) expression is elevated in several
      types of brain tumors, including adult and pediatric GBM, as is the production of
      TF-containing microparticles (TF-MPs). Both TF expression and its vesicular
      emission are regulated by tumor microenvironment (e.g., hypoxia), in concert with
      activated oncogenic and growth factor pathways (RAS, EGFR, MET), as well as the
      loss of tumor suppressor gene activity (PTEN). Discovery of distinct oncogenic
      networks led to recognition of unique molecular subtypes within brain tumors, of
      which GBM (proneural, neural, classical, and mesenchymal), and medulloblastoma
      (SHH, WNT, group 3, and group 4) exhibit subtype-specific composition of the
      tumor coagulome. It remains to be established whether mechanisms of thrombosis
      and biological effects of coagulation in brain tumors are also subtype specific.
      In this regard, TF pathway represents a paradigm, and its impact on tumor
      dormancy, inflammation, angiogenesis, formation of cancer stem cell niches, and
      dissemination is a subject of considerable interest. However, establishing the
      extent to which TF and TF-MPs contribute to pathogenesis and thromboembolic
      disease in the context of primary and secondary brain tumors may require
      molecular stratification of patient populations. We suggest that a better
      understanding of these molecular linkages may pave the way to a more effective
      (targeted) therapy, prophylaxis, adjunctive use of anticoagulants, and other
      agents able to modulate interactions between brain tumors and the coagulation
      system. 

PMID- 24108472
TI  - Brain hemorrhages in cerebral amyloid angiopathy.
AB  - Cerebral amyloid angiopathy (CAA) is cerebrovascular amyloid deposition. It is
      classified into several types according to the cerebrovascular amyloid proteins
      involved. Sporadic amyloid beta-protein (Abeta)-type CAA is commonly found in
      elderly individuals and patients with Alzheimer disease. CAA-related disorders
      include hemorrhagic and ischemic stroke and dementia. CAA-related hemorrhages
      include intracerebral lobar macrohemorrhages, cortical microhemorrhages, and
      focal subarachnoidal hemorrhages/superficial siderosis. CAA-associated
      vasculopathies, such as microaneurysmal formation with fibrinoid necrosis,
      underlie such cerebrovascular events. Sensitive magnetic resonance imaging
      procedures, such as gradient-echo T2* imaging and susceptibility-weighted images,
      are useful to detect microhemorrhagic lesions. Amyloid images with amyloid
      binding positron emission tomography ligands can detect CAA, although they cannot
      discriminate vascular from parenchymal amyloid deposits. Hemorrhage-inducing
      factors for sporadic Abeta-type CAA include apolipoprotein E genotype,
      thrombolytic, anticoagulation, and antiplatelet therapies, hypertension, minor
      head trauma, and antiamyloid therapies. We need future strategies for protection
      of vessel walls against amyloid-related vascular damage, such as toxicity of
      Abeta oligomers, Abeta-induced oxidative stress, and inflammation, as well as
      development of antiamyloid therapies for CAA. 

PMID- 24108474
TI  - Reply: To PMID 23446990.

PMID- 24108476
TI  - A Fully Reconfigurable Low-Noise Biopotential Sensing Amplifier With 1.96 Noise
      Efficiency Factor.
AB  - A fully reconfigurable biopotential sensing amplifier utilizing floating-gate
      transistors is presented in this paper. By using the complementary differential
      pairs along with the current reuse technique, the theoretical limit for the noise
      efficiency factor of the proposed amplifier is below 1.5. Without consuming any
      extra power, floating-gate transistors are employed to program the low-frequency
      cutoff corner of the amplifier and to implement the common-mode feedback. A
      concept proving prototype chip was designed and fabricated in a 0.35 MUm CMOS
      process occupying 0.17 mm (2) silicon area. With a supply voltage of 2.5 V, the
      measured midband gain is 40.7 dB and the measured input-referred noise is 2.8
      MUVrms. The chip was tested under several configurations with the amplifier
      bandwidth being programmed to 100 Hz, 1 kHz , and 10 kHz. The measured noise
      efficiency factors in these bandwidth settings are 1.96, 2.01, and 2.25,
      respectively, which are among the best numbers reported to date. The measured
      common-mode rejection and the supply rejection are above 70 dB . When the
      bandwidth is configured to be 10 kHz, the dynamic range measured at 1 kHz is 60
      dB with total harmonic distortion less than 0.1%. The proposed amplifier is also
      demonstrated by recording electromyography (EMG), electrocardiography (ECG),
      electrooculography (EOG), and electroencephalography (EEG) signals from human
      bodies.

PMID- 24108475
TI  - Spectroscopic and molecular modeling studies of the interaction between morin and
      polyamidoamine dendrimer.
AB  - Interactions between the polyamidoamine (PAMAM) dendrimer and drug molecules are
      of interest for their potential biomedical applications. The goal of this work is
      to examine the interaction of PAMAM-C12 25% dendrimer with morin. The ultraviolet
      visible, fluorescence spectroscopic methods as well as molecular modeling were
      used to analyze drug-binding mode, binding constants and binding sites, etc. The
      experimental data showed that the binding constant of morin-PAMAM-C12 25% is
      about 10(5) L/mol. The interaction of morin with PAMAM-C12 25% is mainly driven
      by the hydrophobic, electrostatic, hydrogen bonds and van der Waals forces. There
      are mainly three classes of binding site of morin at the interface of PAMAM-C12
      25%. These results provided some useful information for self-assembling and
      disassembling the PAMAM dendrimer as well as efficient drug delivery and
      therapeutic applications.

PMID- 24108477
TI  - A 0.7-V 17.4- MU W 3-lead wireless ECG SoC.
AB  - This paper presents a fully integrated sub-1 V 3-lead wireless ECG System-on-Chip
      (SoC) for wireless body sensor network applications. The SoC includes a two
      channel ECG front-end with a driven-right-leg circuit, an 8-bit SAR ADC, a custom
      designed 16-bit microcontroller, two banks of 16 kb SRAM, and a MICS band
      transceiver. The microcontroller and SRAM blocks are able to operate at sub-/near
      threshold regime for the best energy consumption. The proposed SoC has been
      implemented in a standard 0.13- MU m CMOS process. Measurement results show the
      microcontroller consumes only 2.62 pJ per instruction at 0.35 V . Both
      microcontroller and memory blocks are functional down to 0.25 V. The entire SoC
      is capable of working at single 0.7-V supply. At the best case, it consumes 17.4
      MU W in heart rate detection mode and 74.8 MUW in raw data acquisition mode under
      sampling rate of 500 Hz. This makes it one of the best ECG SoCs among state-of
      the-art biomedical chips. 

PMID- 24108478
TI  - Quality by design for herbal drugs: a feedforward control strategy and an
      approach to define the acceptable ranges of critical quality attributes.
AB  - INTRODUCTION: The concept of quality by design (QbD) has been widely accepted and
      applied in the pharmaceutical manufacturing industry. There are still two key
      issues to be addressed in the implementation of QbD for herbal drugs. The first
      issue is the quality variation of herbal raw materials and the second issue is
      the difficulty in defining the acceptable ranges of critical quality attributes
      (CQAs). OBJECTIVE: To propose a feedforward control strategy and a method for
      defining the acceptable ranges of CQAs for the two issues. METHODS: In the case
      study of the ethanol precipitation process of Danshen (Radix Salvia miltiorrhiza)
      injection, regression models linking input material attributes and process
      parameters to CQAs were built first and an optimisation model for calculating the
      best process parameters according to the input materials was established. Then,
      the feasible material space was defined and the acceptable ranges of CQAs for the
      previous process were determined. RESULTS: In the case study, satisfactory
      regression models were built with cross-validated regression coefficients (Q(2) )
      all above 91 %. The feedforward control strategy was applied successfully to
      compensate the quality variation of the input materials, which was able to
      control the CQAs in the 90-110 % ranges of the desired values. In addition, the
      feasible material space for the ethanol precipitation process was built
      successfully, which showed the acceptable ranges of the CQAs for the
      concentration process. CONCLUSION: The proposed methodology can help to promote
      the implementation of QbD for herbal drugs.

PMID- 24108479
TI  - Virtual reality exposure therapy for the treatment of posttraumatic stress
      disorder: a methodological review using CONSORT guidelines.
AB  - CONTEXT: Virtual reality exposure therapy (VRET) is an extension of traditional
      exposure therapy and has been used to treat a variety of anxiety disorders. VRET
      utilizes a computer-generated virtual environment to present fear-relevant
      stimuli. Recent studies have evaluated the use of VRET for treatment of PTSD;
      however, a systematic evaluation of the methodological quality of these studies
      has yet to be conducted. OBJECTIVES: This review aims to (a) identify treatment
      outcome studies examining the use of VRET for the treatment of PTSD and (b)
      appraise the methodological quality of each study using the 2010 Consolidating
      Standards of Reporting Trials (CONSORT) Statement and its 2008 extension for
      nonpharmacologic interventions. METHODS: Two independent assessors conducted a
      database search (PsycINFO, Medline, CINAHL, Google Scholar) of studies published
      between January 1990 and June 2013 that reported outcome data comparing VRET with
      another type of treatment or a control condition. Next, a CONSORT quality
      appraisal of each study was completed. RESULTS: The search yielded nine unique
      studies. The CONSORT appraisal revealed that the methodological quality of
      studies examining VRET as a treatment for PTSD was variable. CONCLUSION: Although
      preliminary findings suggest some positive results for VRET as a form of exposure
      treatment for PTSD, additional research using well-specified randomization
      procedures, assessor blinding, and monitoring of treatment adherence is
      warranted. Movement toward greater standardization of treatment manuals, virtual
      environments, and equipment would further facilitate interpretation and
      consolidation of this literature.

PMID- 24108480
TI  - A theoretical study on the structure, intramolecular interactions, and detonation
      performance of hydrazinium dinitramide.
AB  - The structures of hydrazinium dinitramide (HDN) in the gas phase and in aqueous
      solution have been studied at different levels of theory by using quantum
      chemistry. The intramolecular hydrogen-bond interactions in HDN were studied by
      employing the quantum theory of atoms in molecules (QTAIM), as well as those in
      ammonium dinitramide (ADN), hydrazinium nitroformate (HNF), and ammonium
      nitroformate (ANF) for comparison. The results showed that HDN possessed the
      strongest hydrogen bonds, with the largest hydrogen-bond energy (-47.95 kJ mol(
      1)) and the largest total hydrogen-bond energy (-60.29 kJ mol(-1)). In addition,
      the charge transfer between the cation and the anion, the binding energy, the
      energy difference between the frontier orbitals, and the second-order
      perturbation energy of HDN were all the largest among the investigated compounds.
      These strongest intramolecular interactions accounted for the highest
      decomposition temperature of HDN among all four compounds. The IR spectra in the
      gas phase and in aqueous solution were very different and showed the significant
      influence of the solvent. The UV spectrum showed the strongest absorption at
      about 253 nm. An orbital-interaction diagram demonstrated that the transition of
      electrons mainly happened inside the anion of HDN. The detonation velocity
      (D=8.34 km s(-1)) and detonation pressure (P=30.18 GPa) of HDN were both higher
      than those of ADN (D=7.55 km s(-1) and P=24.83 GPa). The composite explosive
      HDN/CL-20 with the weight ratio wCL-20 /wHDN =0.388:0.612 showed the best
      performance (D=9.36 km s(-1) , P=39.82 GPa), which was close to that of CL-20
      (D=9.73 km s(-1), P=45.19 GPa) and slightly better than that of the composite
      explosive ADN/CL-20 (wCL-20 /wADN =0.298:0.702, D=9.34 km s(-1), P=39.63 GPa).

PMID- 24108482
TI  - Detection of respiratory arousals using photoplethysmography (PPG) signal in
      sleep apnea patients.
AB  - Respiratory events during sleep induce cortical arousals and manifest changes in
      autonomic markers in sleep disorder breathing (SDB). Finger photoplethysmography
      (PPG) has been shown to be a reliable method of determining sympathetic
      activation. We hypothesize that changes in PPG signals are sufficient to predict
      the occurrence of respiratory-event-related cortical arousal. In this study, we
      develop a respiratory arousal detection model in SDB subjects by using PPG
      features. PPG signals from 10 SDB subjects (9 male, 1 female) with age range 43
      75 years were used in this study. Time domain features of PPG signals, such as 1)
      PWA--pulse wave amplitude, 2) PPI--peak-to-peak interval, and 3) Area--area under
      peak, were used to detect arousal events. In this study, PWA and Area have shown
      better performance (higher accuracy and lower false rate) compared to PPI
      features. After investigating possible groupings of these features, combination
      of PWA and Area (PWA + Area) was shown to provide better accuracy with a lower
      false detection rate in arousal detection. PPG-based arousal indexes agreed well
      across a wide range of decision thresholds, resulting in a receiver operating
      characteristic with an area under the curve of 0.91. For the decision threshold
      (PC(thresh) = 25%) chosen for the final analyses, a sensitivity of 68.1% and a
      specificity of 95.2% were obtained. The results showed an accuracy of 84.68%,
      85.15%, 86.93%, and 50.79% with a false rate of 21.80%, 55.41%, 64.78%, and
      50.79% at PC(thresh) = 25% or PPI, PWA, Area , and PWA + Area features,
      respectively. This indicates that combining PWA and Area features reduced the
      false positive rate without much affecting the sensitivity of the arousal
      detection system. In conclusion, the PPG-based respiratory arousal detection
      model is a simple and promising alternative to the conventional
      electroencephalogram (EEG)-based respiratory arousal detection system.

PMID- 24108481
TI  - The assistant function of three-dimensional information for I125 particle
      implantation.
AB  - The purpose of this study was to explore the assistant function of 3-D
      information for I125 particle implantation of multineedle intervention under the
      guidance of ultrasound. The assistant function of 3-D information was verified by
      a simulation experiment system which consists of an ultrasound probe, an
      abdominal phantom, the preoperative computed tomography image of a patient, the
      electromagnetic tracking device, and the self-developed 3-D image navigation
      software with a practical and friendly graphical user interface. The simulation
      particle implantation experiments were divided into the two groups. The first
      group of experiments was performed with the aid of 3-D information. Seven days
      later, the second group of experiments was carried out with the aid of 2-D
      information. We made the statistical analysis of the experimental results
      obtained by nine medical students, nine interventional radiologists, and nine
      attending physicians. With the assistance of 3-D information, the percentage of
      tumor coverage increased (p < 0.01), the operation time shortened (p < 0.01), and
      the number of insertions reduced (p < 0.01). The assistant function of 3-D
      information for particle implantation of multineedle intervention under the
      guidance of ultrasound was technically feasible and effective.

PMID- 24108483
TI  - Designing an architecture for monitoring patients at home: ontologies and web
      services for clinical and technical management integration.
AB  - This paper presents the design and implementation of an architecture based on the
      combination of ontologies, rules, web services, and the autonomic computing
      paradigm to manage data in home-based telemonitoring scenarios. The architecture
      includes two layers: 1) a conceptual layer and 2) a data and communication layer.
      On the one hand, the conceptual layer based on ontologies is proposed to unify
      the management procedure and integrate incoming data from all the sources
      involved in the telemonitoring process. On the other hand, the data and
      communication layer based on REST web service (WS) technologies is proposed to
      provide practical backup to the use of the ontology, to provide a real
      implementation of the tasks it describes and thus to provide a means of
      exchanging data (support communication tasks). A case study regarding chronic
      obstructive pulmonary disease data management is presented in order to evaluate
      the efficiency of the architecture. This proposed ontology-based solution defines
      a flexible and scalable architecture in order to address main challenges
      presented in home-based telemonitoring scenarios and thus provide a means to
      integrate, unify, and transfer data supporting both clinical and technical
      management tasks.

PMID- 24108484
TI  - Design and evaluation of RFID deployments in a trauma resuscitation bay.
AB  - We examined configuring a radio frequency identification (RFID) equipment for the
      best object use detection in a trauma bay. Unlike prior work on RFID, we 1)
      optimized the accuracy of object use detection rather than just object detection;
      and 2) quantitatively assessed antenna placement while addressing issues specific
      to tag placement likely to occur in a trauma bay. Our design started with an
      analysis of the environment requirements and constraints. We designed several
      antenna setups with different number of components (RFID tags or antennas) and
      their orientations. Setups were evaluated under scenarios simulating a dynamic
      medical setting. We used three metrics with increasing complexity and bias: read
      rate, received signal strength indication distribution distance, and target
      application performance. Our experiments showed that antennas above the regions
      with high object density are most suitable for detecting object use. We explored
      tagging strategies for challenging objects so that sufficient readout rates are
      obtained for computing evaluation metrics. Among the metrics, distribution
      distance was correlated with target application performance, and also less biased
      and simpler to calculate, which made it an excellent metric for context-aware
      applications. We present experimental results obtained in the real trauma bay to
      validate our findings. 

PMID- 24108486
TI  - [Abstracts of the Fall Meeting of the DGK and the Annual Meeting of the Working
      Group for Pacemakers and Arrhythmia. October 10-12, 2013. Dresden, Germany ].

PMID- 24108485
TI  - Making a pragmatic choice for fluid resuscitation in critically ill patients.

PMID- 24108487
TI  - Suicide: the long and winding road from research to practice.

PMID- 24108488
TI  - Suicide among United States military personnel: determining the root causes.

PMID- 24108489
TI  - Anxiety disorders are independently associated with suicide ideation and
      attempts: propensity score matching in two epidemiological samples.
AB  - BACKGROUND: Research suggests that suicidal behavior in individuals with anxiety
      disorders is attributable to co-occurring risk factors, such as depression. We
      argue that these conclusions are founded primarily in statistical adjustments
      that may obscure independent associations. We explored independent associations
      between specific anxiety disorders and suicide attempts and ideation by means of
      propensity score matching, a process that simulates a case-control study by
      creating matched groups that differ in group status (e.g., diagnosis of a
      specific anxiety disorder) but that are statistically equivalent on observed
      covariates. METHODS: We made use of the National Comorbidity Survey Replication
      (NCS-R) and the National Epidemiologic Survey on Alcohol and Related Conditions
      (NESARC), which include a total of 43,935 adults. Diagnoses included agoraphobia
      without panic disorder, generalized anxiety disorder, panic disorder with or
      without agoraphobia, posttraumatic stress disorder, social anxiety disorder, and
      specific phobia. RESULTS: Each anxiety disorder was (95% confidence intervals)
      associated with increased odds of lifetime suicide attempts (odds ratios 3.57
      6.64 [NCS-R], 3.03-7.00 [NESARC]) and suicidal ideation (odds ratios 2.62-4.87
      [NCS-R], 3.34-10.57 [NESARC]). Odds ratios for each disorder remained
      statistically significant after matching on diagnostic status of dysthymia, major
      depressive disorder, alcohol abuse/dependence, substance abuse/dependence,
      bipolar disorder I, bipolar disorder II, all other anxiety disorders, and on
      sociodemographic variables. CONCLUSIONS: This is the first report to present
      evidence that each anxiety disorder is associated with suicide ideation and
      suicide attempts beyond the effects of co-occurring mental disorders. These
      findings warrant consideration in assessment, intervention, and related policies.

PMID- 24108491
TI  - A scatter learning particle swarm optimization algorithm for multimodal problems.
AB  - Particle swarm optimization (PSO) has been proved to be an effective tool for
      function optimization. Its performance depends heavily on the characteristics of
      the employed exemplars. This necessitates considering both the fitness and the
      distribution of exemplars in designing PSO algorithms. Following this idea, we
      propose a novel PSO variant, called scatter learning PSO algorithm (SLPSOA) for
      multimodal problems. SLPSOA contains some new algorithmic features while
      following the basic framework of PSO. It constructs an exemplar pool (EP) that is
      composed of a certain number of relatively high-quality solutions scattered in
      the solution space, and requires particles to select their exemplars from EP
      using the roulette wheel rule. By this means, more promising solution regions can
      be found. In addition, SLPSOA employs Solis and Wets' algorithm as a local
      searcher to enhance its fine search ability in the newfound solution regions. To
      verify the efficiency of the proposed algorithm, we test it on a set of 16
      benchmark functions and compare it with six existing typical PSO algorithms.
      Computational results demonstrate that SLPSOA can prevent premature convergence
      and produce competitive solutions. 

PMID- 24108492
TI  - Triplex transfer learning: exploiting both shared and distinct concepts for text
      classification.
AB  - Transfer learning focuses on the learning scenarios when the test data from
      target domains and the training data from source domains are drawn from similar
      but different data distributions with respect to the raw features. Along this
      line, some recent studies revealed that the high-level concepts, such as word
      clusters, could help model the differences of data distributions, and thus are
      more appropriate for classification. In other words, these methods assume that
      all the data domains have the same set of shared concepts, which are used as the
      bridge for knowledge transfer. However, in addition to these shared concepts,
      each domain may have its own distinct concepts. In light of this, we systemically
      analyze the high-level concepts, and propose a general transfer learning
      framework based on nonnegative matrix trifactorization, which allows to explore
      both shared and distinct concepts among all the domains simultaneously. Since
      this model provides more flexibility in fitting the data, it can lead to better
      classification accuracy. Moreover, we propose to regularize the manifold
      structure in the target domains to improve the prediction performances. To solve
      the proposed optimization problem, we also develop an iterative algorithm and
      theoretically analyze its convergence properties. Finally, extensive experiments
      show that the proposed model can outperform the baseline methods with a
      significant margin. In particular, we show that our method works much better for
      the more challenging tasks when there are distinct concepts in the data. 

PMID- 24108493
TI  - Feature selection inspired classifier ensemble reduction.
AB  - Classifier ensembles constitute one of the main research directions in machine
      learning and data mining. The use of multiple classifiers generally allows better
      predictive performance than that achievable with a single model. Several
      approaches exist in the literature that provide means to construct and aggregate
      such ensembles. However, these ensemble systems contain redundant members that,
      if removed, may further increase group diversity and produce better results.
      Smaller ensembles also relax the memory and storage requirements, reducing
      system's run-time overhead while improving overall efficiency. This paper extends
      the ideas developed for feature selection problems to support classifier ensemble
      reduction, by transforming ensemble predictions into training samples, and
      treating classifiers as features. Also, the global heuristic harmony search is
      used to select a reduced subset of such artificial features, while attempting to
      maximize the feature subset evaluation. The resulting technique is systematically
      evaluated using high dimensional and large sized benchmark datasets, showing a
      superior classification performance against both original, unreduced ensembles,
      and randomly formed subsets. 

PMID- 24108496
TI  - Tolerance profiles and immunosuppression.

PMID- 24108494
TI  - Diseases attributable to asbestos exposure: years of potential life lost, United
      States, 1999-2010.
AB  - BACKGROUND: Although asbestos use has been restricted in recent decades, asbestos
      associated deaths continue to occur in the United States. OBJECTIVES: We
      evaluated premature mortality and loss of potentially productive years of life
      attributable to asbestos-associated diseases. METHODS: Using 1999-2010 National
      Center for Health Statistics mortality data, we identified decedents aged >=25
      years whose death certificate listed asbestosis and malignant mesothelioma as the
      underlying cause of death. We computed years of potential life lost to life
      expectancy (YPLL) and to age 65 (YPLL65 ). RESULTS: During 1999-2010, a total of
      427,005 YPLL and 55,184 YPLL65 were attributed to asbestosis (56,907 YPLL and
      2,167 YPLL65 ), malignant mesothelioma (370,098 YPPL and 53,017 YPLL65 ). Overall
      and disease-specific asbestos-attributable total YPLL and YPLL65 and median YPLL
      and YPLL65 per decedent did not change significantly from 1999 to 2010.
      CONCLUSIONS: The continuing occurrence of asbestos-associated diseases and their
      substantial premature mortality burden underscore the need for maintaining
      prevention efforts and for ongoing surveillance to monitor temporal trends in
      these diseases.

PMID- 24108498
TI  - Rh-catalyzed aldehyde-aldehyde cross-aldol reaction under base-free conditions:
      in situ aldehyde-derived enolate formation through orthogonal activation.
AB  - The chemoselective generation of aldehyde-derived enolates to realize an aldehyde
      aldehyde cross-aldol reaction is described. A combined Rh/dippf system
      efficiently promoted the isomerization/aldol sequence by using primary allylic,
      homoallylic, and bishomoallylic alcohols; secondary allylic and homoallylic
      alcohols; and trialkoxyboranes that were derived from primary allylic and
      homoallylic alcohols. The reaction proceeded at ambient temperature under base
      free conditions, thus giving cross-aldol products with high chemoselectivity.
      Mechanistic studies, as well as its application to double-aldol processes under
      protecting-group-free conditions, are also described.

PMID- 24108497
TI  - HPLC profiling with at-line microdilution assay for the early identification of
      anti-fungal compounds in plants from French Polynesia.
AB  - INTRODUCTION: The search for anti-fungal compounds has maintained a scientific
      interest notably due to existing difficulties in the treatment of mycoses and
      their increasing occurrence in hospitals. OBJECTIVE: Development of a simple
      method to rapidly identify anti-fungal compounds in crude plant extracts based on
      a HPLC microfractionation approach combined with an at-line anti-Candida assay.
      METHODS: The scale of the semi-preparative HPLC microfractionation was adapted to
      fit the sensitivity of the Candida albicans anti-fungal in a 96-well
      microdilution assay. This format is also compatible for MS and NMR dereplication
      of the active compounds. RESULTS: Based on the screening of 12 crude extracts of
      plants from French Polynesia, three plants, which displayed various levels of
      anti-fungal activities, were selected to assess the efficiency of the HPLC anti
      fungal profiling and the scale necessary for microfractionation. The same anti
      Candida assay was performed on the HPLC microfractions collected using a generic
      profiling method. Analysis of active microfractions by MS and NMR issued from the
      most active extract enabled an efficient dereplication of the compounds
      responsible for the anti-fungal activity. CONCLUSION: A generic HPLC anti-fungal
      profiling method was developed which revealed that only 50 mg of crude extract
      were sufficient for a rapid identification of compound(s) responsible for the
      anti-Candida activity. This approach was illustrated by the study of Alphitonia
      zizyphoides, a plant traditionally used to treat dermatomycoses.

PMID- 24108499
TI  - Crystal structures of starch binding domain from Rhizopus oryzae glucoamylase in
      complex with isomaltooligosaccharide: insights into polysaccharide binding
      mechanism of CBM21 family.
AB  - Glucoamylases are responsible for hydrolysis of starch and polysaccharides to
      yield beta-D-glucose. Rhizopus oryzae glucoamylase (RoGA) is composed of an N
      terminal starch binding domain (SBD) and a C-terminal catalytic domain connected
      by an O-glycosylated linker. Two carbohydrate binding sites in RoSBD have been
      identified, site I is created by three highly conserved aromatic residues, Trp47,
      Tyr83, and Tyr94, and site II is built up by Tyr32 and Phe58. Here, the two
      crystal structures of RoSBD in complex with only alpha-(1,6)-linked
      isomaltotriose (RoSBD-isoG3) and isomaltotetraose (RoSBD-isoG4) have been
      determined at 1.2 and 1.3 A, respectively. Interestingly, site II binding is
      observed in both complexes, while site I binding is only found in the RoSBD-isoG4
      complex. Hence, site II acts as the recognition binding site for carbohydrate and
      site I accommodates site II to bind isoG4. Site I participates in sugar binding
      only when the number of glucosyl units of oligosaccharides is more than three.
      Taken together, two carbohydrate binding sites in RoSBD cooperate to reinforce
      binding mode of glucoamylase with polysaccharides as well as the starch.

PMID- 24108500
TI  - Are all units created equal?

PMID- 24108501
TI  - Acute skeletal muscle wasting in critical illness.
AB  - IMPORTANCE: Survivors of critical illness demonstrate skeletal muscle wasting
      with associated functional impairment. OBJECTIVE: To perform a comprehensive
      prospective characterization of skeletal muscle wasting, defining the pathogenic
      roles of altered protein synthesis and breakdown. DESIGN, SETTING, AND
      PARTICIPANTS: Sixty-three critically ill patients (59% male; mean age: 54.7 years
      [95% CI, 50.0-59.6 years]) with an Acute Physiology and Chronic Health Evaluation
      II score of 23.5 (95% CI, 21.9-25.2) were prospectively recruited within 24 hours
      following intensive care unit (ICU) admission from August 2009 to April 2011 at a
      university teaching and a community hospital in England. Patients were recruited
      if older than 18 years and were anticipated to be intubated for longer than 48
      hours, to spend more than 7 days in critical care, and to survive ICU stay. MAIN
      OUTCOMES AND MEASURES: Muscle loss was determined through serial ultrasound
      measurement of the rectus femoris cross-sectional area (CSA) on days 1, 3, 7, and
      10. In a subset of patients, the fiber CSA area was quantified along with the
      ratio of protein to DNA on days 1 and 7. Histopathological analysis was
      performed. In addition, muscle protein synthesis, breakdown rates, and respective
      signaling pathways were characterized. RESULTS: There were significant reductions
      in the rectus femoris CSA observed at day 10 (-17.7% [95% CI, -25.9% to 8.1%]; P
      < .001). In the 28 patients assessed by all 3 measurement methods on days 1 and
      7, the rectus femoris CSA decreased by 10.3% (95% CI, 6.1% to 14.5%), the fiber
      CSA by 17.5% (95% CI, 5.8% to 29.3%), and the ratio of protein to DNA by 29.5%
      (95% CI, 13.4% to 45.6%). Decrease in the rectus femoris CSA was greater in
      patients who experienced multiorgan failure by day 7 (-15.7%; 95% CI, -27.7% to
      11.4%) compared with single organ failure (-3.0%; 95% CI, -5.3% to 2.1%) (P <
      .001), even by day 3 (-8.7% [95% CI, -59.3% to 50.6%] vs -1.8% [95% CI, -12.3% to
      10.5%], respectively; P = .03). Myofiber necrosis occurred in 20 of 37 patients
      (54.1%). Protein synthesis measured by the muscle protein fractional synthetic
      rate was depressed in patients on day 1 (0.035%/hour; 95% CI, 0.023% to
      0.047%/hour) compared with rates observed in fasted healthy controls
      (0.039%/hour; 95% CI, 0.029% to 0.048%/hour) (P = .57) and increased by day 7
      (0.076% [95% CI, 0.032%-0.120%/hour]; P = .03) to rates associated with fed
      controls (0.065%/hour [95% CI, 0.049% to 0.080%/hour]; P = .30), independent of
      nutritional load. Leg protein breakdown remained elevated throughout the study
      (8.5 [95% CI, 4.7 to 12.3] to 10.6 [95% CI, 6.8 to 14.4] MUmol of
      phenylalanine/min/ideal body weight * 100; P = .40). The pattern of intracellular
      signaling supported increased breakdown (n = 9, r = -0.83, P = .005) and
      decreased synthesis (n = 9, r = -0.69, P = .04). CONCLUSIONS AND RELEVANCE: Among
      these critically ill patients, muscle wasting occurred early and rapidly during
      the first week of critical illness and was more severe among those with
      multiorgan failure compared with single organ failure. These findings may provide
      insights into skeletal muscle wasting in critical illness.

PMID- 24108502
TI  - Proposal of a new disease concept "biliary diseases with pancreatic
      counterparts". Anatomical and pathological bases.
AB  - The biliary tract and pancreas are located closely anatomically, and both develop
      from the endoderm foregut almost at the same time. Interestingly, the lining
      epithelia of the bile duct and main pancreatic duct show similar morphologies and
      phenotypes, and both are accompanied by periductal glands. Furthermore, the
      exocrine pancreatic acini are remnantly found in the peribiliary glands. Based on
      these findings, it seems plausible that the biliary tract has features of
      pancreatic elements in addition to the duct system, which is specialized for the
      drainage of bile secreted by hepatic parenchyma, particularly, hepatocytes.
      Interestingly, some pancreatic and biliary diseases show similar pathological
      features and even biological behaviors. For example, extrahepatic
      cholangiocarcinoma and ductal adenocarcinoma of the pancreas share many
      clinicopathological features. Both of them are hypothesized to arise from similar
      preneoplastic and early neoplastic intraepithelial lesions. Intraductal papillary
      tumors, with frequent mucin hyperproduction, develop in the pancreas (intraductal
      papillary mucinous neoplasm) and also in the biliary tract (intraductal papillary
      neoplasm of the bile duct). IgG4-related disease affects the biliary tract (IgG4
      related sclerosing cholangitis) and the pancreas (autoimmune pancreatitis) in the
      same patients, with both showing similar morphologies. Herein, we propose that
      these non-neoplastic and neoplastic biliary diseases showing similarities to
      corresponding pancreatic diseases could be included in a new disease concept
      "biliary diseases with pancreatic counterparts". Based on this new concept,
      information obtained in biliary tract diseases could be applied to the analysis
      of pancreatic disease and vice versa, and also novel therapeutical strategies and
      molecular and genetic studies on pancreatic and biliary diseases may be developed
      with a unified approach.

PMID- 24108503
TI  - Ex situ NMR relaxometry of metal-organic frameworks for rapid surface-area
      screening.

PMID- 24108504
TI  - Methotrexate-induced nausea and vomiting in adolescent and young adult patients.
AB  - This study aims to determine the prevalence of methotrexate-induced nausea and
      vomiting in both adolescent and adult patients with inflammatory arthritis. A
      survey of methotrexate side effects was conducted on patients with inflammatory
      arthritis. We provided a brief questionnaire to unselected patients with
      inflammatory arthritis being treated with methotrexate attending adolescent and
      adult rheumatology clinics. The questions related to the presence, absence, and
      severity of nausea and vomiting, the temporal relationship with methotrexate and
      whether anti-emetics had been prescribed. A total of 106 patients from the age of
      13 years and above--57 adults (over 20 years) and 49 adolescents (13-19 years)
      were included in this study. The median age for those experiencing nausea was 19
      years (interquartile range (IQR) 7) and for those with no nausea 55 years (IQR
      46) (p < 0.001). Thirty-six out of 49 adolescent patients reported nausea (73%)
      compared to only 20/57 adults (35%) (p < 0.001). Multiple logistic regression
      analysis showed that the nausea group had a significantly higher proportion of
      adolescents (p = 0.0002), patients taking subcutaneous (SC) methotrexate MTX (p =
      0.002), and patients with duration of MTX of more than 1 year (p = 0.049).
      Adolescents were estimated to have over 6 times higher odds of nausea compared to
      adults (OR 6.31, 95% CI 2.38 to 16.75, p = 0.0002) after adjusting for SC MTX and
      duration of MTX. Only 22% of adolescents and 10% of adults were prescribed anti
      emetics. There is a higher prevalence of MTX-induced nausea and vomiting in
      adolescents and younger adult patients with inflammatory arthritis compared to
      older adults. The role of anti-emetics in the treatment of these symptoms is
      unclear.

PMID- 24108505
TI  - The impact of asbestos exposure in Swedish construction workers.
AB  - OBJECTIVE: To study the occurrence of pleural mesothelioma as a measure of the
      impact on health from asbestos exposure in the construction industry. METHODS:
      The occurrence of pleural mesothelioma in different occupations, time periods and
      birth cohorts was studied in a cohort of construction workers. They were
      prospectively followed after they had participated in health examinations between
      1971 and 1993. The analysis was restricted to men and in total 367,568 men was
      included in the analysis. RESULTS: In total there were 419 cases of pleural
      mesotheliomas between 1972 and 2009. As expected the age adjusted incidence was
      high in insulation workers and plumbers (39 and 16 cases per 100,000 person
      years, respectively). However, only 21% of the pleural mesotheliomas occurred in
      those occupational groups. Occupational groups with many cases of pleural
      mesothelioma were concrete workers (N = 56), wood workers (N = 55), painters (N =
      32), electricians (N = 48), and foremen (N = 37). The highest risk was in birth
      cohorts born between 1935 and 1945. Between 1995 and 2009 around one-third of all
      male cases in the country occurred in this birth cohort. The risk seemed to
      decrease considerably in men born after 1955. CONCLUSION: In Sweden a
      considerable proportion of pleural mesotheliomas occur among construction
      workers; and not only in jobs traditionally associated with asbestos exposure
      such as insulators and plumbers but also among electricians, for example. The
      results shows that asbestos exposure occurs in many occupational groups,
      indicating that safe handling of asbestos is a very difficult or even impossible
      task in the construction industry.

PMID- 24108508
TI  - Laser microdissection: a sample preparation technique for plant micrometabolic
      profiling.
AB  - INTRODUCTION: Unlike unicellular organisms, plants have evolved as complex
      organisms that are defined by their ability to distribute special vital functions
      to spatially separated organs and tissues. Current phytochemical approaches
      mostly ignore this fact by analysing samples that consist of different cell types
      and thus average the information obtained. A comprehensive metabolite analysis
      with high spatial resolution is essential to fully characterise the state of a
      certain tissue; hence, the analysis of metabolites occurring in specialised plant
      cells is of considerable interest in chemical ecology, plant natural product
      chemistry and other bioscience disciplines. Laser microdissection (LMD),
      including laser capture microdissection and laser microdissection and pressure
      catapulting, is a convenient sampling technique to harvest homogeneous cell types
      for the microanalysis of plant metabolites. OBJECTIVE: The objective of this work
      is to provide an introduction to LMD methodology and a concise review of recent
      applications of LMD in the high-resolution analysis of metabolites in different
      plant materials. METHODS: A step-by-step approach to LMD sampling techniques is
      described. How LMD can be used to sample cells or microscopic tissue pieces from
      different plant organs, such as leaves, stems, and seeds, is shown in detail.
      Finally, the future of LMD in plant metabolites analysis is discussed. RESULTS:
      This review summarises studies over the past decade not only showing technical
      details but also indicating the wide application of this method for high
      resolution plant metabolite analysis. CONCLUSION: Laser microdissection is a
      powerful sampling technique for plant micrometabolic profiling and metabolomics
      research.

PMID- 24108509
TI  - Direct synthesis of sorbitol and glycerol from cellulose over ionic Ru/magnetite
      nanoparticles in the absence of external hydrogen.
AB  - A sweet catalyst: A catalyst formed of Ru/functionalized silica-coated magnetite
      nanoparticles is highly efficient in the one-pot production of sorbitol and
      glycerol, starting from cellulose and in the absence of an external hydrogen
      source. The ease of recoverability of the catalyst from the solid residues, and
      its reuse without loss of activity or selectivity for several runs, is an
      important green element of the process. 

PMID- 24108511
TI  - Antibiotics for the prophylaxis of bacterial endocarditis in dentistry.
AB  - BACKGROUND: Infective endocarditis is a severe infection arising in the lining of
      the chambers of the heart with a high mortality rate.Many dental procedures cause
      bacteraemia and it was believed that this may lead to bacterial endocarditis (BE)
      in a few people. Guidelines in many countries have recommended that prior to
      invasive dental procedures antibiotics are administered to people at high risk of
      endocarditis. However, recent guidance by the National Institute for Health and
      Care Excellence (NICE) in England and Wales has recommended that antibiotics are
      not required. OBJECTIVES: To determine whether prophylactic antibiotic
      administration, compared to no such administration or placebo, before invasive
      dental procedures in people at risk or at high risk of bacterial endocarditis
      influences mortality, serious illness or the incidence of endocarditis. SEARCH
      METHODS: The following electronic databases were searched: the Cochrane Oral
      Health Group's Trials Register (to 21 January 2013), the Cochrane Central
      Register of Controlled Trials (CENTRAL) (The Cochrane Library 2012, Issue 12),
      MEDLINE via OVID (1946 to 21 January 2013) and EMBASE via OVID (1980 to 21
      January 2013). We searched for ongoing trials in the US National Institutes of
      Health Trials Register (http://clinicaltrials.gov) and the metaRegister of
      Controlled Trials (http://www.controlled-trials.com/mrct/). No restrictions were
      placed on the language or date of publication when searching the electronic
      databases. SELECTION CRITERIA: Due to the low incidence of BE it was anticipated
      that few if any trials would be located. For this reason, cohort and case-control
      studies were included where suitably matched control or comparison groups had
      been studied. The intervention was the administration of antibiotic, compared to
      no such administration, before a dental procedure in people with an increased
      risk of BE. Cohort studies would need to follow those individuals at increased
      risk and assess outcomes following any invasive dental procedures, grouping by
      whether prophylaxis was received or not. Included case-control studies would need
      to match people who had developed endocarditis (and who were known to be at
      increased risk before undergoing an invasive dental procedure preceding the onset
      of endocarditis) with those at similar risk but who had not developed
      endocarditis. Outcomes of interest were mortality or serious adverse events
      requiring hospital admission; development of endocarditis following any dental
      procedure in a defined time period; development of endocarditis due to other non
      dental causes; any recorded adverse events to the antibiotics; and cost
      implications of the antibiotic provision for the care of those patients who
      developed endocarditis. DATA COLLECTION AND ANALYSIS: Two review authors
      independently selected studies for inclusion then assessed risk of bias and
      extracted data from the included study. MAIN RESULTS: No randomised controlled
      trials (RCTs), controlled clinical trials (CCTs) or cohort studies were included.
      One case-control study met the inclusion criteria. It collected all the cases of
      endocarditis in the Netherlands over two years, finding a total of 24 people who
      developed endocarditis within 180 days of an invasive dental procedure,
      definitely requiring prophylaxis according to current guidelines, and who were at
      increased risk of endocarditis due to a pre-existing cardiac problem. This study
      included participants who died because of the endocarditis (using proxies).
      Controls attended local cardiology outpatient clinics for similar cardiac
      problems, had undergone an invasive dental procedure within the past 180 days,
      and were matched by age with the cases. No significant effect of penicillin
      prophylaxis on the incidence of endocarditis could be seen. No data were found on
      other outcomes. AUTHORS' CONCLUSIONS: There remains no evidence about whether
      antibiotic prophylaxis is effective or ineffective against bacterial endocarditis
      in people at risk who are about to undergo an invasive dental procedure. It is
      not clear whether the potential harms and costs of antibiotic administration
      outweigh any beneficial effect. Ethically, practitioners need to discuss the
      potential benefits and harms of antibiotic prophylaxis with their patients before
      a decision is made about administration.

PMID- 24108510
TI  - Effect of statin therapy on mortality in patients with ventilator-associated
      pneumonia: a randomized clinical trial.
AB  - IMPORTANCE: Observational studies have reported that statin use may be associated
      with improved outcomes of various infections. Ventilator-associated pneumonia
      (VAP) is the most common infection in the intensive care unit (ICU) and is
      associated with substantial mortality. OBJECTIVE: To determine whether statin
      therapy can decrease day-28 mortality in patients with VAP. DESIGN, SETTING, AND
      PARTICIPANTS: Randomized, placebo-controlled, double-blind, parallel-group,
      multicenter trial performed in 26 intensive care units in France from January
      2010 to March 2013. For power to detect an 8% absolute reduction in the day-28
      mortality rate, we planned to enroll 1002 patients requiring invasive mechanical
      ventilation for more than 2 days and having suspected VAP, defined as a modified
      Clinical Pulmonary Infection Score of 5 or greater. The futility stopping rules
      were an absolute increase in day-28 mortality of at least 2.7% with simvastatin
      compared with placebo after enrollment of the first 251 patients. INTERVENTIONS:
      Participants were randomized to receive simvastatin (60 mg) or placebo, started
      on the same day as antibiotic therapy and given until ICU discharge, death, or
      day 28, whichever occurred first. MAIN OUTCOMES AND MEASURES: Primary outcome was
      day-28 mortality. Day-14, ICU, and hospital mortality rates were determined, as
      well as duration of mechanical ventilation and Sequential Organ Failure
      Assessment (SOFA) scores on days 3, 7, and 14. RESULTS: The study was stopped for
      futility at the first scheduled interim analysis after enrollment of 300
      patients, of whom all but 7% in the simvastatin group and 11% in the placebo
      group were naive to statin therapy at ICU admission. Day-28 mortality was not
      lower in the simvastatin group (21.2% [95% CI, 15.4% to 28.6%) than in the
      placebo group (15.2% [95% CI, 10.2% to 22.1%]; P = .10; hazard ratio, 1.45 [95%
      CI, 0.83 to 2.51]); the between-group difference was 6.0% (95% CI, -3.0% to
      14.9%). In statin-naive patients, day-28 mortality was 21.5% (95% CI, 15.4% to
      29.1%) with simvastatin and 13.8% (95% CI, 8.8% to 21.0%) with placebo (P = .054)
      (between-group difference, 7.7% [95%CI, -1.8% to 16.8%). There were no
      significant differences regarding day-14, ICU, or hospital mortality rates;
      duration of mechanical ventilation; or changes in SOFA score. CONCLUSIONS AND
      RELEVANCE: In adults with suspected VAP, adjunctive simvastatin therapy compared
      with placebo did not improve day-28 survival. These findings do not support the
      use of statins with the goal of improving VAP outcomes. TRIAL REGISTRATION:
      clinicaltrials.gov Identifier: NCT01057758.

PMID- 24108512
TI  - Multiple tense bullae localized to the right breast in a woman in her seventies.

PMID- 24108513
TI  - The holy grail in genetic toxicology: follow-up approaches for positive results
      in the Ames assay.
AB  - Positive results in the Ames/E. coli bacterial mutagenicity assay create a
      significant hurdle for the development of new products/drugs and as a result,
      most companies drop mutagenic ingredients from further development. One important
      consequence of this is that the understanding of the human relevance of chemicals
      that are positive in the Ames assay is not increasing at the pace seen with
      ingredients that are positive in the other in vitro genotoxicity assays. Recent
      advances in defining thresholds for mutagenic carcinogens, along with new assays
      for measuring mutagenicity in vivo suggests it is time to direct more attention
      to the holy grail of clearly defining practical approaches to address positive
      results in the Ames assay. To stimulate further discussion and research in this
      area, a review of the most current thinking on approaches for dealing with Ames
      positive results is provided along with some suggestions for the way forward.

PMID- 24108514
TI  - Formation of a new benzotriquinane skeleton via intramolecular photocycloaddition
      reactions of a phenylethynes moiety to a 1-cyanonaphthalene ring system.
AB  - Photoirradiation of 1-cyano-2-(2,2-dicyano-5-phenylpentyn-4-yl)naphthalene and
      its analogues promotes sequential intramolecular [2pi + 2pi] photocycloaddition
      and cyclobutene ring opening to form benzocyclooctatetraenes, which are then
      transformed to benzotriquinanes in good yields via a photochemical transannular
      cyclization process. 

PMID- 24108515
TI  - Effects of fluid resuscitation with colloids vs crystalloids on mortality in
      critically ill patients presenting with hypovolemic shock: the CRISTAL randomized
      trial.
AB  - IMPORTANCE: Evidence supporting the choice of intravenous colloid vs crystalloid
      solutions for management of hypovolemic shock remains unclear. OBJECTIVE: To test
      whether use of colloids compared with crystalloids for fluid resuscitation alters
      mortality in patients admitted to the intensive care unit (ICU) with hypovolemic
      shock. DESIGN, SETTING, AND PARTICIPANTS: A multicenter, randomized clinical
      trial stratified by case mix (sepsis, trauma, or hypovolemic shock without sepsis
      or trauma). Therapy in the Colloids Versus Crystalloids for the Resuscitation of
      the Critically Ill (CRISTAL) trial was open label but outcome assessment was
      blinded to treatment assignment. Recruitment began in February 2003 and ended in
      August 2012 of 2857 sequential ICU patients treated at 57 ICUs in France,
      Belgium, North Africa, and Canada; follow-up ended in November 2012.
      INTERVENTIONS: Colloids (n = 1414; gelatins, dextrans, hydroxyethyl starches, or
      4% or 20% of albumin) or crystalloids (n = 1443; isotonic or hypertonic saline or
      Ringer lactate solution) for all fluid interventions other than fluid maintenance
      throughout the ICU stay. MAIN OUTCOMES AND MEASURES: The primary outcome was
      death within 28 days. Secondary outcomes included 90-day mortality; and days
      alive and not receiving renal replacement therapy, mechanical ventilation, or
      vasopressor therapy. RESULTS: Within 28 days, there were 359 deaths (25.4%) in
      colloids group vs 390 deaths (27.0%) in crystalloids group (relative risk [RR],
      0.96 [95% CI, 0.88 to 1.04]; P = .26). Within 90 days, there were 434 deaths
      (30.7%) in colloids group vs 493 deaths (34.2%) in crystalloids group (RR, 0.92
      [95% CI, 0.86 to 0.99]; P = .03). Renal replacement therapy was used in 156
      (11.0%) in colloids group vs 181 (12.5%) in crystalloids group (RR, 0.93 [95% CI,
      0.83 to 1.03]; P = .19). There were more days alive without mechanical
      ventilation in the colloids group vs the crystalloids group by 7 days (mean: 2.1
      vs 1.8 days, respectively; mean difference, 0.30 [95% CI, 0.09 to 0.48] days; P =
      .01) and by 28 days (mean: 14.6 vs 13.5 days; mean difference, 1.10 [95% CI, 0.14
      to 2.06] days; P = .01) and alive without vasopressor therapy by 7 days (mean:
      5.0 vs 4.7 days; mean difference, 0.30 [95% CI, -0.03 to 0.50] days; P = .04) and
      by 28 days (mean: 16.2 vs 15.2 days; mean difference, 1.04 [95% CI, -0.04 to
      2.10] days; P = .03). CONCLUSIONS AND RELEVANCE: Among ICU patients with
      hypovolemia, the use of colloids vs crystalloids did not result in a significant
      difference in 28-day mortality. Although 90-day mortality was lower among
      patients receiving colloids, this finding should be considered exploratory and
      requires further study before reaching conclusions about efficacy. TRIAL
      REGISTRATION: clinicaltrials.gov Identifier: NCT00318942.

PMID- 24108516
TI  - Exposed surfaces on shape-controlled ceria nanoparticles revealed through AC-TEM
      and water-gas shift reactivity.
AB  - Aberration-corrected transmission electron microscopy and high-angle annular dark
      field imaging was used to investigate the surface structures and internal defects
      of CeO2 nanoparticles (octahedra, rods, and cubes). Further, their catalytic
      reactivity in the water-gas shift (WGS) reaction and the exposed surface sites by
      using FTIR spectroscopy were tested. Rods and octahedra expose stable (111)
      surfaces whereas cubes have primarily (100) facets. Rods also had internal voids
      and surface steps. The exposed planes are consistent with observed reactivity
      patterns, and the normalized WGS reactivity of octahedra and rods were similar,
      but the cubes were more reactive. In situ FTIR spectroscopy showed that rods and
      octahedra exhibit similar spectra for -OH groups and that carbonates and formates
      formed upon exposure to CO whereas for cubes clear differences were observed.
      These results provide definitive information on the nature of the exposed
      surfaces in these CeO2 nanostructures and their influence on the WGS reactivity.

PMID- 24108517
TI  - Low-density macroporous foams obtained from a molecular sieve by temperature
      induced amorphization.

PMID- 24108518
TI  - A global logrank test for adaptive treatment strategies based on observational
      studies.
AB  - In studying adaptive treatment strategies, a natural question that is of
      paramount interest is whether there is any significant difference among all
      possible treatment strategies. When the outcome variable of interest is time-to
      event, we propose an inverse probability weighted logrank test for testing the
      equivalence of a fixed set of pre-specified adaptive treatment strategies based
      on data from an observational study. The weights take into account both the
      possible selection bias in an observational study and the fact that the same
      subject may be consistent with more than one treatment strategy. The asymptotic
      distribution of the weighted logrank statistic under the null hypothesis is
      obtained. We show that, in an observational study where the treatment selection
      probabilities need to be estimated, the estimation of these probabilities does
      not have an effect on the asymptotic distribution of the weighted logrank
      statistic, as long as the estimation of the parameters in the models for these
      probabilities is n-consistent. Finite sample performance of the test is assessed
      via a simulation study. We also show in the simulation that the test can be
      pretty robust to misspecification of the models for the probabilities of
      treatment selection. The method is applied to analyze data on antidepressant
      adherence time from an observational database maintained at the Department of
      Veterans Affairs' Serious Mental Illness Treatment Research and Evaluation
      Center.

PMID- 24108519
TI  - Unexpected cononsolvency behavior of poly (N-isopropylacrylamide)-based
      microgels.
AB  - Poly (N-isopropylacrylamide) (pNIPAm)-based microgels undergo a transition from
      fully water swollen (solvated) to deswollen (desolvated) as the temperature of
      the water they are dissolved in is increased >32  degrees C. In this submission,
      we examine how the temperature of this transition, i.e., the volume phase
      transition temperature (VPTT), depends on the concentration of methanol (MeOH) in
      water the microgels are dissolved in. To accomplish this, pNIPAm-based etalons
      are utilized, and it is shown that the VPTT for the microgels is much less than
      that previously observed for linear pNIPAm and pNIPAm-based microgels.
      Furthermore, and most interestingly, it is determined that the microgels can
      collapse in solutions containing high MeOH (>~65% MeOH) concentration. This is in
      contrast to previous studies, which show that no VPTT is observed for pNIPAm in
      aqueous solutions containing >~65% MeOH. 

PMID- 24108520
TI  - Upregulation of glutamate transporter GLT-1 by mTOR-Akt-NF-kB cascade in
      astrocytic oxygen-glucose deprivation.
AB  - Excessive extracellular glutamate leads to neuronal death in central nervous
      system. Excitatory glutamate transporter subtype 2 (GLT-1) carries bulk of
      glutamate reuptake in cerebral ischemia. Although GLT-1 expression fluctuates
      during the period of ischemia, little is known about its regulatory mechanism.
      Here we show an up-regulation of GLT-1 via mammalian target of rapamycin (mTOR)
      Akt-nuclear factor-kB (NF-kB) signaling cascade in oxygen glucose deprivation
      (OGD). We found that brief rapamycin treatment significantly increased GLT-1
      expression in cultured astrocytes. Rapamycin increased phosphorylation of raptor
      at Ser792 and decreased phosphorylation of rictor at Thr1135, suggesting that
      both mTOR complex 1 (mTORC1) and mTOR complex 2 (mTORC2) are involved in GLT-1
      expression. This conclusion was further confirmed by raptor and rictor disruption
      experiments. Akt was activated by mTORC1 inhibition and required for GLT-1
      expression because triciribine, a specific inhibitor of Akt, blocked the increase
      of GLT-1 expression. mTOR-Akt cascade then activated NF-kB and increased kB-motif
      binding phosphoprotein (KBBP) expression and GLT-1 transcription. We next
      demonstrated that mTOR-Akt-NF-kB cascade was activated in OGD and subsequently
      caused the upregulation of GLT-1. Supporting evidence included: (1) inhibition of
      Akt or NF-kB occluded OGD-induced GLT-1 upregulation; (2) Raptor knock-down plus
      OGD did not add to the increase of GLT-1 expression; (3) Intact mTORC2 was
      required for GLT-1 enhancement. In summary, our data first showed that mTOR-Akt
      NF-kB cascade played critical roles to up-regulate GLT-1 in OGD. This signaling
      cascade may work to promote glutamate uptake in brain ischemia and
      neurodegenerative diseases.

PMID- 24108521
TI  - Fields of effects of 2 commercial preparations of botulinum toxin type A at equal
      labeled unit doses: a double-blind randomized trial.
AB  - IMPORTANCE: This article provides new data on a controversial issue, the
      influence of doses on the diffusion characteristics of 2 botulinum toxins type A.
      OBJECTIVE To assess the fields of effect of abobotulinumtoxinA and
      onabotulinumtoxinA at the same labeled unit dose (1:1 U) comparing sweat gland
      and muscle activity. DESIGN, SETTING, AND PARTICIPANTS: A prospective, single
      center, randomized, double-blind study was conducted at the Brazilian Center for
      Studies in Dermatology in Porto Alegre, Brazil. The participants included 19
      women. INTERVENTIONS: Each patient received 2 U of abobotulinumtoxinA on one side
      of the forehead and 2 U of onabotulinumtoxinA on the other side. MAIN OUTCOMES
      AND MEASURES: Horizontal and vertical diameter and area of the fields of
      anhidrotic effect, the amplitude of evoked compound muscle action potentials, and
      the 4-point validated Wrinkle Severity Scale were assessed at 28 days. RESULTS:
      The horizontal and vertical diameters of the fields of effect and the areas were
      significantly larger for onabotulinumtoxinA than those obtained for
      abobotulinumtoxinA. There were no significant differences between the products in
      the Wrinkle Severity Scale scores and Evoked Compound Muscle Action Potentials.
      OnabotulinumtoxinA had significantly more diffusion than abobotulinumtoxinA when
      isovolumetric injections of the same labeled unit dose of the products were
      injected. CONCLUSIONS AND RELEVANCE Although many studies state that diffusion is
      product dependent and abobotulinumtoxinA diffuses more than onabotulinumtoxinA,
      findings from the present study confirm that diffusion is dose dependent and the
      more potent dose tested diffuses more. TRIAL REGISTRATION clinicaltrials.gov
      Identifier: NCT01732809.

PMID- 24108523
TI  - Integrated disease management interventions for patients with chronic obstructive
      pulmonary disease.
AB  - BACKGROUND: In people with chronic obstructive pulmonary disease (COPD) there is
      considerable variation in symptoms, limitations and well-being, which often
      complicates medical care. To improve quality of life (QoL) and exercise
      tolerance, while reducing the number of exacerbations, a multidisciplinary
      program including different elements of care is needed. OBJECTIVES: To evaluate
      the effects of integrated disease management (IDM) programs or interventions in
      people with COPD on health-related QoL, exercise tolerance and number of
      exacerbations. SEARCH METHODS: We searched the Cochrane Airways Group Register of
      trials, CENTRAL, MEDLINE, EMBASE and CINAHL for potentially eligible studies
      (last searched 12 April 2012). SELECTION CRITERIA: Randomized controlled trials
      evaluating IDM programs for COPD compared with controls were included. Included
      interventions consisted of multidisciplinary (two or more health care providers)
      and multi-treatment (two or more components) IDM programs with a duration of at
      least three months. DATA COLLECTION AND ANALYSIS: Two review authors
      independently assessed trial quality and extracted data; if required, we
      contacted authors for additional data. We performed meta-analyses using random
      effects modeling. We carried out sensitivity analysis for allocation concealment,
      blinding of outcome assessment, study design and intention-to-treat analysis.
      MAIN RESULTS: A total of 26 trials involving 2997 people were included, with a
      follow-up ranging from 3 to 24 months. Studies were conducted in 11 different
      countries. The mean age of the included participants was 68 years, 68% were male
      and the mean forced expiratory volume in one second (FEV1)% predicted value was
      44.3% (range 28% to 66%). Participants were treated in all types of healthcare
      settings: primary (n = 8), secondary (n = 12), tertiary care (n = 1), and in both
      primary and secondary care (n = 5). Overall, the studies were of high to moderate
      methodological quality.Compared with controls, IDM showed a statistically and
      clinically significant improvement in disease-specific QoL on all domains of the
      Chronic Respiratory Questionnaire after 12 months: dyspnea (mean difference (MD)
      1.02; 95% confidence interval (CI) 0.67 to 1.36); fatigue (MD 0.82; 95% CI 0.46
      to 1.17); emotional (MD 0.61; 95% CI 0.26 to 0.95) and mastery (MD 0.75; 95% CI
      0.38 to 1.12). The St. George's Respiratory Questionnaire (SGRQ) for QoL reached
      the clinically relevant difference of four units only for the impact domain (MD 
      4.04; 95% CI -5.96 to -2.11, P < 0.0001). IDM showed a significantly improved
      disease-specific QoL on the activity domain of the SGRQ: MD -2.70 (95% CI -4.84
      to -0.55, P = 0.01). There was no significant difference on the symptom domain of
      the SGRQ: MD -2.39 (95% CI -5.31 to 0.53, P = 0.11). According to the GRADE
      approach, quality of evidence on the SGRQ was scored as high quality, and on the
      CRQ as moderate quality evidence. Participants treated with an IDM program had a
      clinically relevant improvement in six-minute walking distance of 43.86 meters
      compared with controls after 12 months (95% CI 21.83 to 65.89; P < 0.001,
      moderate quality). There was a reduction in the number of participants with one
      or more hospital admissions over three to 12 months from 27 per 100 participants
      in the control group to 20 (95% CI 15 to 27) per 100 participants in the IDM
      group (OR 0.68; 95% CI 0.47 to 0.99, P = 0.04; number needed to treat = 15).
      Hospitalization days were significantly lower in the IDM group compared with
      controls after 12 months (MD -3.78 days; 95% CI -5.90 to -1.67, P < 0.001).
      Admissions and hospital days were graded as high quality evidence. No adverse
      effects were reported in the intervention group. No difference between groups was
      found on mortality (OR 0.96; 95%CI 0.52 to 1.74). There was insufficient evidence
      to refute or confirm the long term effectiveness of IDM. AUTHORS' CONCLUSIONS: In
      these COPD participants, IDM not only improved disease-specific QoL and exercise
      capacity, but also reduced hospital admissions and hospital days per person.

PMID- 24108522
TI  - Traffic-related air pollution and selected birth defects in the San Joaquin
      Valley of California.
AB  - BACKGROUND: Birth defects are a leading cause of infant morbidity and mortality.
      Studies suggest associations between environmental contaminants and some
      structural anomalies, although evidence is limited and several anomalies have not
      been investigated previously. METHODS: We used data from the California Center of
      the National Birth Defects Prevention Study and the Children's Health and Air
      Pollution Study to estimate the odds of 26 congenital birth defect phenotypes
      with respect to quartiles of seven ambient air pollutant and traffic exposures in
      California during the first 2 months of pregnancy, 1997 to 2006 (874 cases and
      849 controls). We calculated odds ratios (adjusted for maternal race/ethnicity,
      education, and vitamin use; aOR) for 11 phenotypes that had at least 40 cases.
      RESULTS: Few odds ratios had confidence intervals that did not include 1.0. Odds
      of esophageal atresia were increased for the highest versus lowest of traffic
      density (aOR = 2.8, 95% confidence interval [CI], 1.1-7.4) and PM10 exposure (aOR
      4.9; 95% CI, 1.4-17.2). PM10 was associated with a decreased risk of hydrocephaly
      (aOR= 0.3; 95% CI, 0.1-0.9) and CO with decreased risk of anotia/microtia (aOR =
      0.4; 95% CI, 0.2-0.8) and transverse limb deficiency (aOR = 0.4; 95% CI, 0.2
      0.9), again reflecting highest versus lowest quartile comparisons. CONCLUSION:
      Most analyses showed no substantive association between air pollution and the
      selected birth defects with few exceptions of mixed results.

PMID- 24108524
TI  - Biodistribution and dosimetry of 195mPt-cisplatin in normal volunteers. Imaging
      agent for single photon emission computed tomography.
AB  - 195mPt-cisplatin is regarded as a promising imaging agent for optimizing dosage
      in patients receiving cisplatin chemotherapy. METHODS: We investigated the whole
      body distribution and radiation dosimetry of 195mPt-cisplatin in humans. Whole
      body scans were obtained up to 144 h after intravenous injection of 112.4 MBq
      195mPt-cisplatin in each of five subjects. Blood samples were taken at various
      times up to 144 h after injection. Urine was collected up to 114 h after
      injection for calculation of renal clearance and whole-body clearance.
      Time/activity curves were generated by fitting the organ-specific geometric mean
      counts, obtained from regions of interest, on the respective images as a function
      of the time after injection. OLINDA software package was applied to calculate the
      absorbed radiation dose for various organs. RESULTS: Most of the activity (32 +/-
      4%) was excreted in the urine during the first 5 h. The effective clearance half
      life derived from extrapolation of the whole-body curve was 40 hours (1.7 days).
      On average, the highest dose was received by the kidneys (mean dose received 2.68
      +/- 1.5 mGy/MBq), followed by the spleen (mean dose received 1.6 +/- 0.8 mGy/MBq)
      followed by the liver (mean dose received 1.45 +/- 0.38 mGy/MBq). The estimated
      mean effective dose for the adult subject was 0.185 +/- 0.034 mSv/MBq.
      CONCLUSION: 195mPt-cisplatin proved a safe radiopharmaceutical with a favourable
      biodistribution for early and delayed imaging of pathology above the diaphragm.
      The ED obtained was 0.185 +/- 0.034 mSv/MBq. The highest organ dose was received
      by the kidneys (2.68 +/- 1.5 mGy/MBq).

PMID- 24108525
TI  - An unstable paramagnetic isopolyoxomolybdate intermediate non-homogeneously
      reduced at different sites and trapped in a host based on chemical adaptability.

PMID- 24108526
TI  - Effect of heart rate control with esmolol on hemodynamic and clinical outcomes in
      patients with septic shock: a randomized clinical trial.
AB  - IMPORTANCE: beta-Blocker therapy may control heart rate and attenuate the
      deleterious effects of beta-adrenergic receptor stimulation in septic shock.
      However, beta-Blockers are not traditionally used for this condition and may
      worsen cardiovascular decompensation related through negative inotropic and
      hypotensive effects. OBJECTIVE: To investigate the effect of the short-acting
      beta-blocker esmolol in patients with severe septic shock. DESIGN, SETTING, AND
      PATIENTS: Open-label, randomized phase 2 study, conducted in a university
      hospital intensive care unit (ICU) between November 2010 and July 2012, involving
      patients in septic shock with a heart rate of 95/min or higher requiring high
      dose norepinephrine to maintain a mean arterial pressure of 65 mm Hg or higher.
      INTERVENTIONS: We randomly assigned 77 patients to receive a continuous infusion
      of esmolol titrated to maintain heart rate between 80/min and 94/min for their
      ICU stay and 77 patients to standard treatment. MAIN OUTCOMES AND MEASURES: Our
      primary outcome was a reduction in heart rate below the predefined threshold of
      95/min and to maintain heart rate between 80/min and 94/min by esmolol treatment
      over a 96-hour period. Secondary outcomes included hemodynamic and organ function
      measures; norepinephrine dosages at 24, 48, 72, and 96 hours; and adverse events
      and mortality occurring within 28 days after randomization. RESULTS: Targeted
      heart rates were achieved in all patients in the esmolol group compared with
      those in the control group. The median AUC for heart rate during the first 96
      hours was -28/min (IQR, -37 to -21) for the esmolol group vs -6/min (95% CI, -14
      to 0) for the control group with a mean reduction of 18/min (P < .001). For
      stroke volume index, the median AUC for esmolol was 4 mL/m2 (IQR, -1 to 10) vs 1
      mL/m2 for the control group (IQR, -3 to 5; P = .02), whereas the left ventricular
      stroke work index for esmolol was 3 mL/m2 (IQR, 0 to 8) vs 1 mL/m2 for the
      control group (IQR, -2 to 5; P = .03). For arterial lactatemia, median AUC for
      esmolol was -0.1 mmol/L (IQR, -0.6 to 0.2) vs 0.1 mmol/L for the control group
      (IQR, -0.3 for 0.6; P = .007); for norepinephrine, -0.11 MUg/kg/min (IQR, -0.46
      to 0.02) for the esmolol group vs -0.01 MUg/kg/min (IQR, -0.2 to 0.44) for the
      control group (P = .003). Fluid requirements were reduced in the esmolol group:
      median AUC was 3975 mL/24 h (IQR, 3663 to 4200) vs 4425 mL/24 h(IQR, 4038 to
      4775) for the control group (P < .001). We found no clinically relevant
      differences between groups in other cardiopulmonary variables nor in rescue
      therapy requirements. Twenty-eight day mortality was 49.4% in the esmolol group
      vs 80.5% in the control group (adjusted hazard ratio, 0.39; 95% CI, 0.26 to 0.59;
      P < .001). CONCLUSIONS AND RELEVANCE: For patients in septic shock, open-label
      use of esmolol vs standard care was associated with reductions in heart rates to
      achieve target levels, without increased adverse events. The observed improvement
      in mortality and other secondary clinical outcomes warrants further
      investigation. TRIAL REGISTRATION: clinicaltrials.gov Identifier: NCT01231698.

PMID- 24108527
TI  - Galsulfase (Naglazyme(r)) therapy in infants with mucopolysaccharidosis VI.
AB  - OBJECTIVE: To evaluate the efficacy and safety of two dose levels of galsulfase
      (Naglazyme(r)) in infants with MPS VI. STUDY DESIGN: This was a phase 4,
      multicenter, multinational, open-label, two-dose level study. Subjects were
      randomized 1:1 to receive weekly infusions of 1.0 or 2.0 mg/kg of galsulfase for
      a minimum of 52 weeks. Progression of skeletal dysplasia was determined by
      monitoring physical appearance, radiographic changes, and growth. Urinary
      glycosaminoglycan (GAG) levels, gross and fine motor function, cardiac function,
      vision, hearing, and health resource utilization were evaluated. Safety
      assessments were performed. RESULTS: Four infants (aged 3.3-12.7 months)
      participated in the study. Galsulfase was well tolerated at 1.0 and 2.0
      mg/kg/week dose levels with no drug-related serious adverse events. Two subjects
      experienced a total of four possible treatment-related adverse events which were
      all considered mild. Length and weight remained within age-expected norms.
      Skeletal abnormalities continued to progress in all subjects. High baseline
      urinary GAG levels (mean: 870 MUg/mg creatinine) decreased by approximately 70%;
      these reduced levels were maintained (mean: 220 MUg/mg creatinine at week 52)
      despite the development of anti-galsulfase antibodies. Hearing, cardiac function,
      hepatosplenomegaly, and facial dysmorphism stabilized or improved, but corneal
      clouding progressed. There was no clear difference in safety or efficacy between
      the two doses. CONCLUSIONS: Galsulfase at two dose levels was safe and well
      tolerated in infants. Normal growth was maintained but skeletal abnormalities
      continued to progress. Urinary GAG levels decreased with treatment. Early
      initiation of galsulfase may prevent or slow progression of some disease
      manifestations.

PMID- 24108528
TI  - A conditioning platform based on fludarabine, busulfan, and 2 days of rabbit
      antithymocyte globulin results in promising results in patients undergoing
      allogeneic transplantation from both matched and mismatched unrelated donor.
AB  - Conditioning regimen including fludarabine, intravenous busulfan (Bx), and 5
      mg/kg total dose of rabbit antithymocyte globulin (r-ATG) (FBx-ATG) results in
      low incidence of graft-versus-host disease (GVHD) and non-relapse mortality (NRM)
      after allogeneic hematopoietic stem cell transplantation (Allo-HSCT) from HLA
      matched related or unrelated donors (MUD). However, whether this platform
      produces similar results in the setting of one mismatch unrelated donor (MMUD)
      Allo-HSCT is not known. We retrospectively analyzed patients aged less than 65
      years who were diagnosed with hematological malignancies and received FBx-ATG
      regimen prior to Allo-HSCT from MUD (N = 74) or MMUD (N = 40). We compared
      outcome of MUD versus MMUD patients. There was no difference in the cumulative
      incidence of grades II-IV acute GVHD (MUD: 34% vs. MMUD: 35%, P = 0.918), but
      MMUD patients developed more grade III-IV acute GVHD (MUD: 5% vs. MMUD: 15%, P =
      0.016). The cumulative incidences of overall chronic GVHD (MUD: 33% vs. MMUD:
      22%, P = 0.088) and extensive chronic GVHD (MUD: 20% vs. MMUD: 19%, P = 0.594)
      were comparable. One-year NRM was similar in both groups (MUD: 16% vs. MMUD: 14%,
      P = 0.292); similarly, progression-free survival (MUD: 59% vs. MMUD: 55%, P =
      0.476) and overall survival (MUD: 63% vs. MMUD: 61%, P = 0.762) were not
      different between both groups. With a median follow up of 24 months, 35 of 74 MUD
      patients (47%) and 19 of 40 MMUD patients (48%) were free of both disease
      progression and immunosuppressive treatment. We conclude that the FBx-ATG regimen
      results in low incidences of NRM and GVHD in both MUD and the MMUD recipients.

PMID- 24108529
TI  - An unusual origin of the celiac trunk and the superior mesenteric artery in the
      thorax.
AB  - The authors report a case of a 44-year-old male found to have unusual origins of
      the celiac trunk (CT) and superior mesernteric artrery (SMA) as revealed by
      routine multidetector computed tomograph (MDCT) angiography. The CT and SMA
      originate from the thoracic aorta (TA) 21 mm and 9 mm above the aortic hiatus,
      respectively. The median arcuate ligament (MAL) is located at the level of the L1
      L2 intervertebral disc. The course of the CT descends in the thoracic cavity
      making a 14 degrees  acute downward angle in front of the TA; below the level of
      the MAL, the CT descends, making an angle of 47 degrees . The course of the SMA
      descends at both the thoracic and abdominal level making an angle of 17 degrees ,
      and having an aortomesenteric distance of 9 mm at the level of the third part of
      the duodenum. In the present case, the supradiaphragmatic origin of the CT and
      the SMA was determined by their incomplete caudal descent, associated with a
      pronounced apparent descent of the diaphragm. A thoracic origin of the CT and SMA
      and the acute downward aortomesenteric angle (17 degrees ) associated with a
      reduced aortomesenteric distance at the level of the third part of the duodenum
      (9 mm), although no clinical signs are present, may predispose the patient to
      develop simultaneously a triple syndrome: the compression of CT by MAL (celiac
      axis compression syndrome), the compression of SMA by MAL (superior mesenteric
      artery compression syndrome), and the compression of the duodenum by the SMA
      (superior mesenteric artery syndrome).

PMID- 24108531
TI  - Psychological interventions for needle-related procedural pain and distress in
      children and adolescents.
AB  - BACKGROUND: This review is an updated version of the original Cochrane review
      published in Issue 4, 2006. Needle-related procedures are a common source of pain
      and distress for children. Our previous review on this topic indicated that a
      number of psychological interventions were efficacious in managing pediatric
      needle pain, including distraction, hypnosis, and combined cognitive behavioural
      interventions. Considerable additional research in the area has been published
      since that time. OBJECTIVES: To provide an update to our 2006 review assessing
      the efficacy of psychological interventions for needle-related procedural pain
      and distress in children and adolescents. SEARCH METHODS: Searches of the
      following databases were conducted for relevant randomized controlled trials
      (RCTs): Cochrane Central Register of Controlled Trials (CENTRAL); MEDLINE;
      EMBASE; PsycINFO; the Cumulative Index to Nursing and Allied Health Literature
      (CINAHL); and Web of Science. Requests for relevant studies were also posted on
      various electronic list servers. We ran an updated search in March 2012, and
      again in March 2013. SELECTION CRITERIA: Participants included children and
      adolescents aged two to 19 years undergoing needle-related procedures. Only RCTs
      with at least five participants in each study arm comparing a psychological
      intervention group with a control or comparison group were eligible for
      inclusion. DATA COLLECTION AND ANALYSIS: Two review authors extracted data and
      assessed trial quality and a third author helped with data extraction and coding
      for one non-English study. Included studies were coded for quality using the
      Cochrane Risk of bias tool. Standardized mean differences with 95% confidence
      intervals were computed for all analyses using Review Manager 5.2 software. MAIN
      RESULTS: Thirty-nine trials with 3394 participants were included. The most
      commonly studied needle procedures were venipuncture, intravenous (IV) line
      insertion, and immunization. Studies included children aged two to 19 years, with
      the most evidence available for children under 12 years of age. Consistent with
      the original review, the most commonly studied psychological interventions for
      needle procedures were distraction, hypnosis, and cognitive behavioural therapy
      (CBT). The majority of included studies (19 of 39) examined distraction only. The
      additional studies from this review update continued to provide strong evidence
      for the efficacy of distraction and hypnosis. No evidence was available to
      support the efficacy of preparation and information, combined CBT (at least two
      or more cognitive or behavioural strategies combined), parent coaching plus
      distraction, suggestion, or virtual reality for reducing children's pain and
      distress. No conclusions could be drawn about interventions of memory alteration,
      parent positioning plus distraction, blowing out air, or distraction plus
      suggestion, as evidence was available from single studies only. In addition, the
      Risk of bias scores indicated several domains with high or unclear bias scores
      (for example, selection, detection, and performance bias) suggesting that the
      methodological rigour and reporting of RCTs of psychological interventions
      continue to have considerable room for improvement. AUTHORS' CONCLUSIONS:
      Overall, there is strong evidence supporting the efficacy of distraction and
      hypnosis for needle-related pain and distress in children and adolescents, with
      no evidence currently available for preparation and information or both, combined
      CBT, parent coaching plus distraction, suggestion, or virtual reality. Additional
      research is needed to further assess interventions that have only been
      investigated in one RCT to date (that is, memory alteration, parent positioning
      plus distraction, blowing out air, and distraction plus suggestion). There are
      continuing issues with the quality of trials examining psychological
      interventions for needle-related pain and distress.

PMID- 24108532
TI  - Pediatric oncology surveillance imaging: two recommendations. Abandon CT
      scanning, and randomize to imaging or solely clinical follow-up.
AB  - Radiologic assessments in children with cancer provide information crucial to
      patient management at diagnosis and during follow-up. Many studies have now been
      published, however, questioning the usefulness of off-therapy surveillance
      imaging. There is growing concern regarding the hazards from diagnostic
      irradiation to young patients, most notably from CT scanning. In this paper we
      advocate abandoning repeated CT surveillance in young patients with a previously
      treated solid malignancy not arising in the central nervous system. In addition,
      randomized studies of imaging surveillance versus no imaging surveillance
      strategies are needed to determine whether earlier detection of recurrence
      results in improved survival.

PMID- 24108530
TI  - Morpho-physiological criteria divide dentate gyrus interneurons into classes.
AB  - GABAergic inhibitory interneurons control fundamental aspects of neuronal network
      function. Their functional roles are assumed to be defined by the identity of
      their input synapses, the architecture of their dendritic tree, the passive and
      active membrane properties and finally the nature of their postsynaptic targets.
      Indeed, interneurons display a high degree of morphological and physiological
      heterogeneity. However, whether their morphological and physiological
      characteristics are correlated and whether interneuron diversity can be described
      by a continuum of GABAergic cell types or by distinct classes has remained
      unclear. Here we perform a detailed morphological and physiological
      characterization of GABAergic cells in the dentate gyrus, the input region of the
      hippocampus. To achieve an unbiased and efficient sampling and classification we
      used knock-in mice expressing the enhanced green fluorescent protein (eGFP) in
      glutamate decarboxylase 67 (GAD67)-positive neurons and performed cluster
      analysis. We identified five interneuron classes, each of them characterized by a
      distinct set of anatomical and physiological parameters. Cross-correlation
      analysis further revealed a direct relation between morphological and
      physiological properties indicating that dentate gyrus interneurons fall into
      functionally distinct classes which may differentially control neuronal network
      activity.

PMID- 24108533
TI  - Gender, ethnicity and graduate status, and junior doctors' self-reported
      preparedness for clinical practice: national questionnaire surveys.
AB  - OBJECTIVES: Medical schools need to ensure that graduates feel well prepared for
      their first medical job. Our objective was to report on differences in junior
      doctors' self-reported preparedness for work according to gender, ethnicity and
      graduate status. DESIGN: Postal and electronic questionnaires. SETTING: UK.
      PARTICIPANTS: Medical graduates of 2008 and 2009, from all UK medical schools,
      one year after graduation. MAIN OUTCOME MEASURES: The main outcome measure was
      the doctors' level of agreement with the statement that 'My experience at medical
      school prepared me well for the jobs I have undertaken so far', to which
      respondents were asked to reply on a scale from 'strongly agree' to 'strongly
      disagree'. RESULTS: Women were slightly less likely than men to agree that they
      felt well prepared for work (50% of women agreed or strongly agreed vs. 54% of
      men), independently of medical school, ethnicity, graduate entry status and
      intercalated degree status, although they were no more likely than men to regard
      lack of preparedness as having been a problem for them. Adjusting for the other
      subgroup differences, non-white respondents were less likely to report feeling
      well prepared than white (44% vs. 54%), and were more likely to indicate that
      lack of preparedness was a problem (30% non-white vs. 24% white). There were also
      some gender and ethnic differences in preparedness for specific areas of work.
      CONCLUSIONS: The identified gender and ethnic differences need to be further
      explored to determine whether they are due to differences in self-confidence or
      in actual preparedness.

PMID- 24108534
TI  - A toolkit to support the implementation of electronic prescribing systems into UK
      hospitals: preliminary recommendations.

PMID- 24108535
TI  - A case of 'cardiology envy'?

PMID- 24108536
TI  - Primary care delays in diagnosing cancer: what is causing them and what can we do
      about them?

PMID- 24108537
TI  - Sarcoidosis presenting as complete heart block in a 45-year-old farmer: an
      aetiology not to miss.
AB  - Sarcoidosis should always be part of the differential diagnosis when faced with a
      young patient with significant cardiac conduction disease. 

PMID- 24108538
TI  - Compassion in healthcare - lessons from a qualitative study of the end of life
      care of people with dementia.
AB  - OBJECTIVES: A lack of compassion in UK healthcare settings has received much
      recent attention. This study explores the experiences of people with dementia in
      the last year of life and time surrounding death and how the presence and lack of
      compassion, kindness and humanity influenced the experience of care. DESIGN:
      Qualitative in-depth interviews with bereaved informal carers of people with
      dementia. SETTING: United Kingdom. PARTICIPANTS: Forty bereaved carers - 31 women
      and nine men - with an age range of 18-86 years and from wide socioeconomic
      backgrounds participated. MAIN OUTCOME MEASURES: Experiences of carers of care
      for person with dementia during last year of life. RESULTS: The interviews
      highlighted differences and challenges in care settings in providing
      compassionate, humanistic care and the impact of the care experienced by the
      person with dementia during the last year of life on informal carers during the
      bereavement period and beyond. Excellent examples of compassionate care were
      experienced alongside very poor and inhumane practices. CONCLUSION: The concepts
      of compassion, kindness and humanity in dementia care are discussed within the
      paper. The ability to deliver care that is compassionate, kind and humanistic
      exists along a continuum across care settings - examples of excellent care sit
      alongside examples of very poor care and the reasons for this are explored
      together with discussion as to how health and social care staff can be trained
      and supported to deliver compassionate care.

PMID- 24108539
TI  - Effect of F8 B domain gene variants on synthesis, secretion, activity and
      stability of factor VIII protein.
AB  - The B domain of the coagulation factor (F)VIII comprises some unique
      characteristics. Though the B domain is important for processing, intracellular
      transport and secretion of FVIII protein, its role in the coagulation still
      remains unclear. This study aims to investigate the influence of 19 reported B
      domain variants on quantity and quality of expressed FVIII protein. F8 variants
      were transiently expressed in HEK293T cells. Media and cell lysates were
      collected after 72 hours. FVIII synthesis, relative secretion, activity and
      thermostability were analysed in comparison to FVIII wild-type. Eleven of 19
      analysed B domain variants showed normal FVIII activity (FVIII:C), and antigen
      values (40-150 %). Eight variants exhibited a decreased FVIII:C, corresponding to
      a mild phenotype most likely due to impaired expression and secretion mechanism,
      reduced thermostability or combined mechanisms. One variant, p.His1066Tyr, showed
      markedly reduced FVIII antigen in cell lysate. The variants p.Asp845Glu,
      p.His998Gln, and p.Ala1610Ser revealed a significantly decreased relative
      secretion. Additionally, six B domain variants significantly reduced stability of
      FVIII. In conclusion, none of the analysed missense mutations was causative for a
      severe haemophilia A (HA) phenotype. Nevertheless, the mutations p.Asp845Glu,
      p.Pro947Arg, p.Glu1057Lys, p.His1066Tyr, p.Arg1126Trp, p.Arg1329His,
      p.Leu1481Pro, and p.Ala1610Ser resulted in decreased FVIII:C values that may
      explain mild HA phenotypes. 

PMID- 24108540
TI  - Molecular pathology and prostate cancer therapeutics: from biology to bedside.
AB  - Prostate cancer (PCa) is the second most commonly diagnosed malignancy in men and
      has an extremely heterogeneous clinical behaviour. The vast majority of PCas are
      hormonally driven diseases in which androgen signalling plays a central role. The
      realization that castration-resistant prostate cancer (CRPC) continues to rely on
      androgen signalling prompted the development of new, effective androgen blocking
      agents. As the understanding of the molecular biology of PCas evolves, it is
      hoped that stratification of prostate tumours into distinct molecular entities,
      each with its own set of vulnerabilities, will be a feasible goal. Around half of
      PCas harbour rearrangements involving a member of the ETS transcription factor
      family. Tumours without this rearrangement include SPOP mutant as well as SPINK1
      over-expressing subtypes. As the number of targeted therapy agents increases, it
      is crucial to determine which patients will benefit from these interventions and
      molecular pathology will be key in this respect. In addition to directly
      targeting cells, therapies that modify the tumour microenvironment have also been
      successful in prolonging the lives of PCa patients. Understanding the molecular
      aspects of PCa therapeutics will allow pathologists to provide core
      recommendations for patient management.

PMID- 24108541
TI  - Practicing prevention with probiotics.

PMID- 24108543
TI  - Persistence and sorption of imazapyr in three Argentinean soils.
AB  - Imazapyr is a herbicide widely used for weed control in imidazolinone-tolerant
      sunflower. Imazapyr has a high potential for leaching into groundwater because it
      is highly water-soluble, persistent in soil, and only weakly sorbed by soils.
      There is a lack of information available in Argentina concerning groundwater
      leaching of imazapyr. Therefore, the objective of the present study was to
      determine the persistence and sorption of imazapyr in 3 Argentinean soils
      (Tandil, Anguil, and Cerro Azul sites). The presence and concentration of
      imazapyr were determined and quantified by ultra-performance liquid
      chromatography and tandem mass spectrometry. The persistence in soils followed
      the order: Cerro Azul > Tandil > Anguil, with half-life values of 121 d, 75 d,
      and 37 d, respectively. The half-life of imazapyr was negatively associated with
      soil pH and iron and aluminum content, and was positively related to clay
      content. Imazapyr sorption was found to be well described by the Freundlich
      isotherm. Soil pH and clay, iron, and aluminum contents were the main factors
      affecting the sorption of imazapyr. The sorption had a limiting effect on the
      degradation rate. Under certain conditions, the weak sorption and high
      persistence may increase the movement of imazapyr in the soil profile and the
      risk of groundwater pollution.

PMID- 24108544
TI  - Readmissions following pancreatoduodenectomy: it's when things don't go well that
      experienced pancreatic surgeons earn their keep.

PMID- 24108542
TI  - Placental disease and the maternal syndrome of preeclampsia: missing links?
AB  - Preeclampsia remains a significant obstetric risk worldwide. The pathophysiology
      of preeclampsia is complex, with multiple stages involving maladaptations in both
      placental and maternal physiology. The placenta links the pre-clinical stage of
      impaired remodeling of the uterine vasculature, occurring in early pregnancy, to
      the later clinical stages characterised by the maternal syndrome of hypertension
      and proteinuria. This review focuses on some of the recent candidates for the
      missing links in this process. 

PMID- 24108545
TI  - Two cases of neuroblastoma comprising two distinct clones.
AB  - We report two cases of high-risk metastatic neuroblastoma, comprising two
      biologically distinct components in the adrenal primary tumor, which showed clear
      differences not only histologically but also in MYCN amplification and HA
      RAS/TRKA immunoreactivity (Case 1), anaplastic lymphoma kinase (ALK)
      immunoreactivity (Case 2). These two cases with multiple separated components
      were similar to cases classified as ganglioneuroblastoma, nodular subtype (GNBn),
      in terms of composite tumor. Comparable to the GNBn category, the prognosis of
      the patients described here may depend on the components with unfavorable
      histology according to International Neuroblastoma Pathology Classification.
      Further analyses of such composite neuroblastoma cases are important for
      assessing disease prognosis.

PMID- 24108546
TI  - Probably benign breast MRI lesions: frequency, lesion type, and rate of
      malignancy.
AB  - PURPOSE: To determine the frequency, malignancy rate, and imaging characteristics
      of BI-RADS (Breast Imaging Reporting and Data System) 3 MRI detected lesions.
      MATERIALS AND METHODS: A total of 4370 consecutive contrast-enhanced breast MRI
      exams from March 1, 2004, to March 1, 2009, were retrospectively reviewed. The
      study was HIPAA (Health Insurance Portability Accountability Act) compliant and
      Institutional Review Board approved. The frequency of BI-RADS 3 MRI
      interpretations and lesion type, as well as malignancy rate at follow-up were
      calculated. RESULTS: There were 348/4370 (8%) BI-RADS 3 exams performed on 345
      patients. There were 125 foci (35.9%), 52 non-masslike enhancements (14.9%), and
      171 masses (49.1%). There were 207 lesions with biopsy or imaging follow-up of at
      least 24 months (mean, 32 months; range, 6-77 months) of the BI-RADS 3 lesion.
      Five of these 207 (2.4%) lesions were found to be malignant. CONCLUSION: Rate of
      malignancy among BI-RADS 3 MRI exams with follow-up was 2.4%. Types of lesions
      assigned as probably benign were 35.9% foci, 14.9% non-masslike enhancements, and
      49.1% masses.

PMID- 24108547
TI  - Neural stem cells harvested from live brains by antibody-conjugated magnetic
      nanoparticles.
AB  - It stems from the magnetism: The extraction of stem/progenitor cells from the
      brain of live animals is possible using antibodies conjugated to magnetic
      nanoparticles (Ab-MNPs). The Ab-MNPs are introduced to a rat's brain with a
      superfine micro-syringe. The stem cells attach to the Ab-MNPs and are
      magnetically isolated and removed. They can develop into neurospheres and
      differentiate into different types of cells outside the subject body. The rat
      remains alive and healthy. 

PMID- 24108549
TI  - 25th anniversary article: Ion exchange in colloidal nanocrystals.
AB  - We review the progress in ion exchange in a variety of nanocrystal structures
      from the earliest accounts dating back over two decades ago to the present day.
      In recent years the number of groups using this method to form otherwise
      difficult or inaccessible nanoparticle shapes and morphologies has increased
      considerably and the field has experienced a resurgence of interest. Whilst most
      of the early work on cation exchange centered on II-VI materials, the methodology
      has been expanded to cover a far broader range of semiconductor nanocrystals
      including low toxicity I-III-VI materials and the much less facile III-V
      materials. The extent of exchange can be controlled leading to lightly doped
      nanoparticles, alloys, core-shells, segmented rods and dots-in-rods. Progress has
      been driven by a better understanding of the underlying principles of the
      exchange process - from thermodynamic factors (differences in cation
      solubilities); the interactions between ions and transfer agents (solvents,
      ligands, anions, co-dopants); ionic in-diffusion mechanisms and kinetics. More
      recent availability of very detailed electron microscopy coupled with image
      reconstruction techniques has been a valuable tool to investigate the resulting
      heterostructures and internal interfaces. We start by surveying the range of
      synthetic approaches most often used to carry out ion exchange, mainly focusing
      on cation replacement strategies, and then describe the rich variety of
      nanostructures these techniques can bring forth. We also describe some of the
      principles that are used to establish the relative ease of exchange and to
      systematically improve the process where the basic energetics are less favorable.
      To help further the understanding of the underlying fundamentals we have gathered
      together useful data from the literature on solubilities, cation and anion
      hardness, ligand and solvent Lewis acid or base strengths for a wide range of
      chemical species generally used. We offer a perspective on the outlook for the
      field in terms of the emerging applications and the ion exchange derived
      materials that will enable them. 

PMID- 24108550
TI  - Imaging of oncologic emergencies: what every radiologist should know.
AB  - Acute life-threatening conditions in oncology patients may develop either because
      of underlying malignancy or as a complication from treatment. Oncologic
      emergencies can be categorized as metabolic, hematologic, and structural
      conditions. Metabolic and hematologic emergencies are mainly diagnosed on the
      basis of clinical and laboratory findings. Structural pathologic conditions that
      result in bleeding, mechanical compression, or obstruction to the hollow organs,
      such as the trachea and bowel loops, may first be suspected because of clinical
      findings, including decreasing hematocrit levels, difficulty in breathing, and
      abdominal pain; however, performance of imaging studies is critical for timely
      diagnosis and management. Life-threatening conditions of the central nervous
      system (such as cerebral herniation, carcinomatous meningitis, and spinal cord
      compression), thoracic emergent conditions (such as central airway obstruction,
      esophagorespiratory fistula, massive hemoptysis, pulmonary embolism, superior
      vena cava syndrome, and pericardial tamponade), and abdominopelvic emergencies
      (such as uncontrolled intraabdominal hemorrhage, bowel obstruction, intestinal
      perforation, bowel ischemia, intussusception, and urinary tract obstruction) can
      be definitively diagnosed on the basis of projectional or cross-sectional imaging
      findings in appropriate clinical scenarios. Select emergent conditions in cancer
      patients related to chemotherapy and radiation treatment, as well as iatrogenic
      emergencies secondary to either surgery or placement of central venous catheters,
      may also demonstrate characteristic findings at imaging studies. In addition,
      interventional procedures are of great help in the treatment of acute superior
      vena cava syndrome, massive hemoptysis, and uncontrolled intraabdominal
      hemorrhage. Radiologists should be aware of these select, "not to be missed"
      imaging findings of oncologic emergencies to make an accurate, timely diagnosis
      and provide appropriate patient care.

PMID- 24108551
TI  - MR imaging-guided focused ultrasound for treatment of bone metastasis.
AB  - Magnetic resonance (MR) imaging-guided focused ultrasound is an alternative
      noninvasive method for reducing the pain in skeletal metastases. MR imaging
      guided focused ultrasound ablation offers several key advantages over other
      noninvasive treatment modalities. This technology enables the performance of
      three-dimensional treatment planning with MR imaging and continuous temperature
      mapping of treated tissue by using MR thermometry, thereby enabling real-time
      monitoring of thermal damage in the target zone. The concentration of acoustic
      energy on the intact surface of cortical bone produces a rapid temperature
      increase that mediates critical thermal damage to the adjacent periosteum, the
      most innervated component of mature bone tissue. Such thermal ablation has been
      shown to be an extremely effective approach for pain management. Energy delivered
      during MR imaging-guided focused ultrasound ablation and accumulated inside the
      pathologic soft tissue of the metastases can create a variable amount of tissue
      necrosis. This technique has also a potential role in achieving local tumor
      control, allowing remineralization of trabecular bone or reduction in lesion
      size. The current report presents a detailed step-by-step guide for performing MR
      imaging-guided focused ultrasound ablation of bone metastases, including use of
      MR thermometry for monitoring treatment, protocol selection for simple palliation
      of pain or for local tumor control, and a description of imaging features of
      periosteal neurolysis or metastasis ablation. Two case studies are also
      presented: in the first, the technique provided palliation of pain in bone
      metastases, and in the second, the technique achieved tumor control as further
      proof of primary efficacy. MR imaging-guided focused ultrasound ablation is a
      promising method for successful palliation of bone metastasis pain and tumor
      control, because of the bony structure remodeling induced by thermo-related
      coagulative necrosis.

PMID- 24108552
TI  - Ductal carcinoma in situ of the breasts: review of MR imaging features.
AB  - The incidence of ductal carcinoma in situ (DCIS) has increased over the past few
      decades and now accounts for over 20% of newly diagnosed cases of breast cancer.
      Although the detection of DCIS has increased with the advent of widespread
      mammography screening, it is essential to have a more accurate assessment of the
      extent of DCIS for successful breast conservation therapy. Recent studies
      evaluating the detection of DCIS with magnetic resonance (MR) imaging have used
      high spatial resolution techniques and have increasingly been performed to screen
      a high-risk population as well as to evaluate the extent of disease. This work
      has shown that MR imaging is the most sensitive modality currently available for
      identifying DCIS and is more accurate than mammography in evaluating the extent
      of DCIS. MR imaging is particularly sensitive for identifying high-grade and
      intermediate-grade DCIS. DCIS may have variable morphologic features on MR
      images, with non-mass enhancement morphology being the most common manifestation.
      Less commonly, DCIS may also manifest as a mass on MR images, in which case it is
      most likely to be irregular. The kinetics of DCIS are also variable, with fast
      uptake and a plateau curve reported as the most common kinetic pattern.
      Additional MR imaging tools such as diffusion-weighted imaging and quantitative
      kinetic analysis combined with the benefit of high field strength, such as 3 T,
      may increase the sensitivity and specificity of breast MR imaging in the
      detection of DCIS.

PMID- 24108553
TI  - Axillary staging of breast cancer: what the radiologist should know.
AB  - Identifying the presence of axillary node and internal mammary node metastases in
      patients with invasive breast cancer is critical for determining prognosis and
      for deciding on appropriate treatment. Sentinel lymph node biopsy (SLNB) is the
      definitive method to exclude axillary metastases. Patients with positive SLNB
      results generally undergo axillary lymph node dissection (ALND). The benefit of
      preoperative identification of axillary metastases is that it allows the surgeon
      to proceed directly to ALND and to avoid an unnecessary SLNB and the need for a
      second surgical procedure involving the axillary nodes. Knowledge of the
      important anatomic landmarks of the axilla is important in finding and accurately
      reporting suspicious lymph nodes. The pathologic features of nodal metastases
      illuminate the imaging appearances of these nodes, as depicted with all
      modalities. Ultrasonography (US) is the primary imaging modality for evaluating
      axillary nodes. Morphologic criteria, such as cortical thickening, hilar
      effacement, and nonhilar cortical blood flow, are more important than size
      criteria in the identification of metastases. US-guided lymph node sampling,
      especially with core biopsy, is invaluable in confirming the presence of a
      metastasis in a suspicious node. Core biopsy has been shown to be equal in safety
      to fine needle aspiration and has a significantly lower false-negative rate.
      Magnetic resonance imaging is also useful, with the added benefit of providing a
      global view of both axillae. Computed tomography and radionuclide imaging play a
      lesser role in imaging the axilla. Preoperative image-based identification and
      sampling of abnormal lymph nodes that have a high positive predictive value for
      metastases is an extremely important component in the management of patients with
      invasive breast cancer.

PMID- 24108554
TI  - Primary pericardial tumors.
AB  - Primary pericardial tumors are rare and may be classified as benign or malignant.
      The most common benign lesions are pericardial cysts and lipomas. Mesothelioma is
      the most common primary malignant pericardial neoplasm. Other malignant tumors
      include a wide variety of sarcomas, lymphoma, and primitive neuroectodermal
      tumor. When present, signs and symptoms are generally nonspecific. Patients often
      present with dyspnea, chest pain, palpitations, fever, or weight loss. Although
      the imaging approach usually begins with plain radiography of the chest or
      transthoracic echocardiography, the value of these imaging modalities is limited.
      Cross-sectional imaging, on the other hand, plays a key role in the evaluation of
      these lesions. Computed tomography and magnetic resonance imaging allow further
      characterization and may, in some cases, provide diagnostic findings.
      Furthermore, the importance of cross-sectional imaging lies in assessing the
      exact location of the tumor in relation to neighboring structures. Both benign
      and malignant tumors may result in compression of vital mediastinal structures.
      Malignant lesions may also directly invade structures, such as the myocardium and
      great vessels, and result in metastatic disease. Imaging plays an important role
      in the detection, characterization, and staging of pericardial tumors; in their
      treatment planning; and in the posttreatment follow-up of affected patients. The
      prognosis of patients with benign tumors is good, even in the few cases in which
      surgical intervention is required. On the other hand, the length of survival for
      patients with malignant pericardial tumors is, in the majority of cases, dismal.

PMID- 24108555
TI  - Spectrum of pulmonary neuroendocrine proliferations and neoplasms.
AB  - Neuroendocrine neoplasms are ubiquitous tumors found throughout the body, most
      commonly in the gastrointestinal tract followed by the thorax. Neuroendocrine
      cells occur normally in the bronchial and bronchiolar epithelium and may be
      solitary or may occur in clusters. Although neuroendocrine cell proliferations
      may be found in association with chronic lung disease, a broad range of
      neuroendocrine proliferations and neoplasms may occur and exhibit variable
      biologic behavior. Diffuse idiopathic neuroendocrine cell hyperplasia (DIPNECH)
      is a diffuse idiopathic form of neuroendocrine cell hyperplasia and is considered
      a preinvasive lesion that may give rise to carcinoid tumors. Patients with
      DIPNECH are typically older women who may be asymptomatic or may present with
      chronic respiratory symptoms. DIPNECH manifests as multifocal bilateral pulmonary
      micronodules on expiratory high-resolution computed tomographic (CT) images; the
      air trapping is secondary to constrictive bronchiolitis. Carcinoid tumors are low
      grade malignant neoplasms that typically affect symptomatic children and young
      adults. Carcinoids manifest as well-defined pulmonary nodules or masses that are
      often closely related to central bronchi. They may exhibit intrinsic
      calcification and contrast material enhancement at CT, and patients with
      carcinoids may have postobstructive atelectasis and pneumonia. Although typical
      carcinoids are indolent neoplasms and patients have a good prognosis, atypical
      carcinoids are aggressive malignancies with a propensity for metastasis. Both are
      optimally treated with complete surgical excision. Large cell neuroendocrine
      carcinoma and small cell lung cancer are highly aggressive neuroendocrine
      malignancies that usually affect elderly smokers. These tumors manifest with
      large peripheral or central pulmonary masses. Local invasion, intrathoracic
      lymphadenopathy, and distant metastases are frequent at presentation. As a
      result, affected patients may not be candidates for surgical resection, are often
      treated with chemotherapy with or without radiation, and have a poor prognosis.

PMID- 24108556
TI  - Hepatocellular carcinoma: illustrated guide to systematic radiologic diagnosis
      and staging according to guidelines of the American Association for the Study of
      Liver Diseases.
AB  - Hepatocellular carcinoma is a malignancy that predominantly occurs in the setting
      of cirrhosis. Its incidence is rising worldwide. Hepatocellular carcinoma differs
      from most malignancies because it is commonly diagnosed on the basis of imaging
      features alone, without histologic confirmation. The guidelines from the American
      Association for the Study of Liver Diseases (AASLD) are a leading statement for
      the diagnosis and staging of hepatocellular carcinoma, and they have recently
      been updated, incorporating several important changes. AASLD advocates the use of
      the Barcelona Clinic Liver Cancer (BCLC) staging system, which combines validated
      imaging and clinical predictors of survival to determine stage and which links
      staging with treatment options. Each stage of the BCLC system is outlined
      clearly, with emphasis on case examples. Focal liver lesions identified at
      ultrasonographic surveillance in patients with cirrhosis require further
      investigation. Lesions larger than 1 cm should be assessed with multiphasic
      computed tomography or magnetic resonance imaging. Use of proper equipment and
      protocols is essential. Lesions larger than 1 cm can be diagnosed as
      hepatocellular carcinoma from a single study if the characteristic dynamic
      perfusion pattern of arterial hyperenhancement and venous or delayed phase
      washout is demonstrated. If the imaging characteristics of hepatocellular
      carcinoma are not met, the alternate modality should be performed. Biopsy should
      be used if neither modality is diagnostic of hepatocellular carcinoma. Once the
      diagnosis has been made, the cancer should be assigned a BCLC stage, which will
      help determine suitable treatment options. Radiologists require a systematic
      approach to diagnose and stage hepatocellular carcinoma with appropriate accuracy
      and precision.

PMID- 24108557
TI  - Beyond the GIST: mesenchymal tumors of the stomach.
AB  - Intramural gastric masses arise in the wall of the stomach (generally within the
      submucosa or muscularis propria), often with intact overlying mucosa. These
      tumors are typically mesenchymal in origin and have overlapping radiologic
      appearances. A combination of features such as location, attenuation,
      enhancement, and growth pattern may suggest one diagnosis over another.
      Gastrointestinal stromal tumors (GISTs) account for the majority of intramural
      tumors and can vary widely in appearance, from small intraluminal lesions to
      exophytic masses that protrude into the peritoneal cavity, commonly with areas of
      hemorrhage or necrosis. A well-circumscribed mass measuring -70 to -120 HU is a
      lipoma. Leiomyomas usually manifest as low-attenuation masses at the gastric
      cardia. Homogeneous attenuation is a noteworthy characteristic of schwannomas,
      particularly for larger lesions that might otherwise be mistaken for GISTs. A
      hypervascular mass in the antrum is a common manifestation of glomus tumors.
      Hemangiomas are also hypervascular but often manifest in childhood. Inflammatory
      fibroid polyps usually arise as a polypoid mass in the antrum. Inflammatory
      myofibroblastic tumors are infiltrative neoplasms with a propensity for local
      recurrence. Plexiform fibromyxomas are rare, usually antral tumors. Carcinoid
      tumors are epithelial in origin, but often submucosal in location, and therefore
      should be distinguished from other intramural lesions. Multiple carcinoid tumors
      are associated with hypergastrinemia, either in the setting of chronic atrophic
      gastritis or Zollinger-Ellison syndrome. Sporadic solitary carcinoid tumors not
      associated with hypergastrinemia have a higher rate of metastasis.
      Histopathologic analysis, including immunohistochemistry, is usually required for
      diagnosis of intramural masses.

PMID- 24108558
TI  - Metastatic renal cell carcinoma: radiologic findings and assessment of response
      to targeted antiangiogenic therapy by using multidetector CT.
AB  - Recent advances in treatment of metastatic renal cell carcinoma (RCC), such as
      new molecular therapies that use novel antiangiogenic agents, have led to
      revision of the most frequently used guideline to evaluate tumor response to
      therapy: Response Evaluation Criteria in Solid Tumors (RECIST 1.1). Assessment of
      the response of metastatic RCC to therapy has traditionally been based on changes
      in target lesion size. However, the mechanism of action of newer antiangiogenic
      therapies is more cytostatic than cytotoxic, which leads to disease stabilization
      rather than to tumor regression. This change in tumor response makes RECIST 1.1-
      a system whose criteria are based exclusively on tumor size--inadequate to
      discriminate patients with early tumor progression from those with more
      progression-free disease and prolonged survival. New criteria such as changes in
      attenuation, morphology, and structure, as seen at contrast-enhanced
      multidetector computed tomography (CT), are being incorporated into new
      classifications used to assess response of metastatic RCC to antiangiogenic
      therapies. The new classifications provide better assessments of tumor response
      to the new therapies, but they have some limitations. The authors provide a
      practical review of these systems--the Choi, modified Choi, and Morphology,
      Attenuation, Size, and Structure (MASS) criteria--by explaining their differences
      and limitations that may influence the feasibility and reproducibility of these
      classifications. The authors review the use of multidetector CT in the detection
      of metastatic RCC and the different appearances and locations of these lesions.
      They also provide an overview of the new antiangiogenic therapies and their
      mechanisms of action and a brief introduction to functional imaging techniques.
      Functional imaging techniques, especially dynamic contrast-enhanced CT, seem
      promising for assessing response of metastatic RCC to treatment. Nonetheless,
      further studies are needed before functional imaging can be used in routine
      clinical practice.

PMID- 24108559
TI  - Perineural spread in head and neck malignancies: clinical significance and
      evaluation with 18F-FDG PET/CT.
AB  - Certain tumors of the head and neck use peripheral nerves as a direct conduit for
      tumor growth away from the primary site by a process known as perineural spread.
      Perineural spread is associated with decreased survival and a higher risk of
      local recurrence and metastasis. Radiologists play an important role in the
      assessment and management of head and neck cancer, and positron emission
      tomography/computed tomography (PET/CT) with 2-[fluorine 18]fluoro-2-deoxy-d
      glucose (FDG) is part of the work-up and follow-up of many affected patients.
      Awareness of abnormal FDG uptake patterns within the head and neck is fundamental
      for diagnosing perineural spread. The cranial nerves most commonly affected by
      perineural spread are the trigeminal and facial nerves. Risk of perineural spread
      increases with a midface location of the tumor, male gender, increasing tumor
      size, recurrence after treatment, and poor histologic differentiation. Focal or
      linear increased FDG uptake along the V2 division of the trigeminal nerve or
      along the medial surface of the mandible, or asymmetric activity in the
      masticator space, foramen ovale, or Meckel cave should raise suspicion for
      perineural spread. If FDG PET/CT findings suggest perineural spread, the
      radiologist should look at available results of other imaging studies, especially
      magnetic resonance imaging, to confirm the diagnosis. Knowledge of common FDG
      PET/CT patterns of neoplastic involvement along the cranial nerves and potential
      diagnostic pitfalls is of the utmost importance for adequate staging and
      treatment planning.

PMID- 24108560
TI  - Orbital neoplasms in adults: clinical, radiologic, and pathologic review.
AB  - Orbital neoplasms in adults may be categorized on the basis of location and
      histologic type. Imaging features of these lesions often reflect their tissue
      composition. Cavernous malformations (also known as cavernous hemangiomas),
      although not true neoplasms, are the most common benign adult orbital tumor. They
      typically appear as a well-circumscribed, ovoid intraconal mass on cross
      sectional images. Lymphoma, which may be primary or secondary to systemic
      disease, is the most prevalent orbital neoplasm in older adults (>=60 years of
      age). Choroidal melanoma is the most common primary adult ocular malignancy.
      Melanin has intrinsic T1 and T2 shortening effects, classically manifesting with
      hyperintense signal on T1-weighted magnetic resonance (MR) images and with
      hypointense signal on T2-weighted images. However, amelanotic or mildly pigmented
      lesions of melanoma do not demonstrate these characteristic MR imaging features.
      Breast cancer is the most common malignancy to metastasize to the orbit, followed
      by prostate cancer, melanoma, and lung cancer. In women with bilateral
      enophthalmos, metastatic scirrhous breast cancer should be considered in the
      differential diagnosis. Neoplasms that arise from the optic nerve or its sheath
      include glioma and meningioma. At imaging, gliomas often cause fusiform expansion
      of the optic nerve, in which the nerve itself cannot be delineated from the
      lesion. In contrast, meningiomas classically have a "tram-track" configuration,
      whereby the contrast-enhancing tumor is seen alongside the optic nerve. Neoplasms
      that derive from peripheral nerves include schwannoma and neurofibroma, the
      latter of which is associated with neurofibromatosis type 1. MR imaging is
      particularly valuable for evaluation of orbital neoplasms, as it provides
      critical anatomic information about ocular structures involved, perineural
      spread, and intracranial extension. 

PMID- 24108561
TI  - Transoral robotic surgery in head and neck cancer: what radiologists need to know
      about the cutting edge.
AB  - The evolution of oncologic surgical technology has moved toward reducing patient
      morbidity and mortality without compromising oncologic resection or oncologic
      outcomes. The goals in treating head and neck cancer are to cure patients, as
      well as to provide quality of life by improving functional and social outcomes
      through organ-preservation therapies, which may include surgery, chemotherapy,
      and/or radiation therapy. Transoral robotic surgery (TORS) is an emerging
      technique that provides several benefits over existing treatment regimens and
      over open surgery for head and neck cancer, including reductions in operative
      times, blood loss, intensive care unit stays, and overall duration of patient
      hospitalization. Transoral robotic techniques allow wide-view, high-resolution,
      magnified three-dimensional optics for visualization of the mucosal surfaces of
      the head and neck through an endoscope, while avoiding the extensive external
      cervical incisions often required for open surgeries. Radiologists play an
      important role in the successful outcome of these procedures, both before and
      after TORS. Determining a cancer patient's surgical candidacy for TORS requires a
      thorough preoperative radiologic evaluation, coupled with clinical and
      intraoperative assessment. Radiologists must pay particular attention to
      important anatomic landmarks that are clinical blind spots for surgeons.
      Knowledge of the expected postoperative imaging appearances, so that they can be
      distinguished from recurrent disease and second primary tumors, is essential for
      all radiologists involved in the care of these patients. 

PMID- 24108562
TI  - Assessment of liver tumor response to therapy: role of quantitative imaging.
AB  - Quantitative imaging is the analysis of retrieved numeric data from images with
      the goal of reducing subjective assessment. It is an increasingly important
      radiologic tool to assess treatment response in oncology patients. Quantification
      of response to therapy depends on the tumor type and method of treatment.
      Anatomic imaging biomarkers that quantify liver tumor response to cytotoxic
      therapy are based on temporal change in the size of the tumors. Anatomic
      biomarkers have been incorporated into the World Health Organization criteria and
      the Response Evaluation Criteria in Solid Tumors (RECIST) versions 1.0 and 1.1.
      However, the development of novel therapies with different mechanisms of action,
      such as antiangiogenesis or radioembolization, has required new methods for
      measuring response to therapy. This need has led to development of tumor- or
      therapy-specific guidelines such as the Modified CT Response Evaluation (Choi)
      Criteria for gastrointestinal stromal tumors, the European Association for Study
      of the Liver (EASL) criteria, and modified RECIST for hepatocellular carcinoma,
      among many others. The authors review the current quantification criteria used in
      the evaluation of treatment response in liver tumors, summarizing their
      indications, advantages, and disadvantages, and discuss future directions with
      newer methods that have the potential for assessment of treatment response.
      Knowledge of these quantitative methods is important to facilitate pivotal
      communication between oncologists and radiologists about cancer treatment, with
      benefit ultimately accruing to the patient.

PMID- 24108563
TI  - Cardiac complications of oncologic therapy.
AB  - As survival rates continue to increase for patients with childhood and adult
      malignancies, imaging utilization in these patients will likely increase
      substantially. It is important to detect disease recurrence and to recognize the
      potential complications that occur after treatment with oncologic medications and
      therapeutic radiation. The most common cardiotoxic side effect of the
      anthracycline drug class is a dose-dependent decline in ejection fraction, which
      may result in dilated cardiomyopathy. Multiple-uptake gated acquisition (MUGA)
      scanning plays an important role in diagnosis of this subclinical cardiac
      dysfunction. Other less common cardiotoxic side effects of chemotherapeutic
      medications include arrhythmia, myocarditis, coronary artery disease, tamponade,
      pericarditis, and pericardial effusion. Radiation therapy can also lead to
      cardiotoxicity when the heart or pericardium is included in the radiation portal.
      Radiation-induced conditions include pericardial disease, coronary artery
      disease, valvular disease, and cardiomyopathy. Many of these side effects are
      asymptomatic until late in the course of the disease. With imaging, these
      pathologic conditions can often be diagnosed before symptom onset, which may
      allow early intervention. Radiologists should be familiar with the current
      knowledge and pathophysiology regarding cardiac complications related to
      chemotherapy and radiation therapy of malignant neoplasms and the appearances of
      treatment-related cardiotoxicity that can be found at radiography, nuclear
      medicine examinations, and cross-sectional imaging. Supplemental material
      available at http://radiographics.rsna.org/lookup/suppl/doi:10.1148/rg.336125005/
      /DC1.

PMID- 24108564
TI  - Identifying and distinguishing treatment effects and complications from
      malignancy at FDG PET/CT.
AB  - Fluorine 18 fluorodeoxyglucose (FDG) positron emission tomography/computed
      tomography (PET/CT) is increasingly used in the initial staging, evaluation of
      treatment response, and surveillance of many malignancies. Uptake of FDG is
      substantially increased in most malignancies, compared with its uptake in normal
      tissues, and the finding of FDG avidity often leads to cancer detection earlier
      than abnormalities can be seen at anatomic imaging. However, FDG is not a cancer
      specific agent, and FDG avidity can be seen in many benign processes. It can be
      particularly challenging to discriminate malignancy from benign FDG-avid changes
      caused by surgery and procedures, radiation therapy, and chemotherapy. FDG-avid
      abnormalities caused by surgery and procedures include inflammation at sites of
      incision or dissection, inflammation from vascular compromise or surgical
      retraction, surgical transposition of structures with physiologic FDG avidity
      (such as ovaries or testes), and pleurodesis inflammation. Radiation therapy may
      induce FDG-avid pneumonitis, esophagitis, or hepatitis, as well as
      osteoradionecrosis or fractures. FDG-avid chemotherapy complications include
      pneumonitis, osteonecrosis, enterocolitis, and pancreatitis. Use of granulocyte
      colony stimulating factor for treatment of bone marrow suppression after
      chemotherapy induces temporary increases of FDG avidity in the bone marrow and
      spleen. Familiarity with common and unusual iatrogenic causes of FDG avidity that
      can confound interpretation of FDG PET/CT results will improve the accuracy of
      distinguishing treatment effects and complications from residual or recurrent
      malignancy at FDG PET/CT examinations. 

PMID- 24108565
TI  - Novel antiplatelet drugs in clinical development.
AB  - The clinical value of antiplatelet compounds strongly depends on the benefit-risk
      balance between their anti-thrombotic effects and the bleeding risk they incur.
      This ratio is especially important in the treatment of cerebro-vascular disease.
      Several novel compounds in clinical development hold promise to improve this
      benefit-risk ratio. 

PMID- 24108566
TI  - Identification of folding intermediates of streblin, the most stable serine
      protease: biophysical analysis.
AB  - Streblin, a serine proteinase from plant Streblus asper, has been used to
      investigate the conformational changes induced by pH, temperature, and
      chaotropes. The near/far UV circular dichroism activities under fluorescence
      emission spectroscopy and 8-aniline-1-naphthalene sulfonate (ANS) binding have
      been carried out to understand the unfolding of the protein in the presence of
      denaturants. Spectroscopic studies reveal that streblin belongs to the alpha+beta
      class of proteins and exhibits stability towards chemical denaturants, guanidine
      hydrochloride (GuHCl). The pH-induced transition of this protein is
      noncooperative for transition phases between pH 0.5 and 2.5 (midpoint, 1.5) and
      pH 2.5 and 10.0 (midpoint, 6.5). At pH 1.0 or lower, the protein unfolds to form
      acid-unfolded state, and for pH 7.5 and above, protein turns into an alkaline
      denatured state characterized by the absence of ANS binding. At pH 2.0 (1 M
      GuHCl), streblin exists in a partially unfolded state with characteristics of a
      molten globule state. The protein is found to exhibit strong and predominant ANS
      binding. In total, six different intermediate states has been identified to show
      protein folding pathways. 

PMID- 24108567
TI  - Geriatric risk assessment in surgery: keeping it simple.

PMID- 24108568
TI  - Comparative morbidity and mortality from cervical or thoracic esophageal
      anastomoses.
AB  - BACKGROUND: In the modern era of esophagectomy, we hypothesized that
      perioperative morbidity and mortality from cervical or thoracic sites of
      anastomoses would not be different. METHODS: We used the American College of
      Surgeons National Surgical Quality Improvement Program database to identify
      patients who underwent esophagectomy for lower esophageal or gastroesophageal
      (GE) junction malignancies from 2005 to 2010. Patients were categorized as having
      either a cervical or thoracic anastomosis based on CPT codes. RESULTS: There were
      601 (66%) cervical and 308 (34%) thoracic anastomoses. Cervical anastomoses were
      associated with greater than 2 units of blood transfusion in a higher proportion
      of patients (10% vs. 3%, P = 0.001), and higher superficial surgical site
      infections (13% vs. 7%, P = 0.003). There were no difference in rates of
      organ/space infections (6% vs. 7%, P = 0.70), overall morbidity (38% vs. 39%, P =
      0.84), or mortality (3% vs. 4%, P = 0.34). Median length of stay was similar
      (11.5 days cervical vs. 11 days thoracic, P = 0.89), even among patients with
      organ/space infections (18 days cervical vs. 21 days thoracic, P = 0.49). On
      multivariate analysis thoracic anastomosis was not a significant predictor of
      increased overall morbidity (OR 1.13: 95%CI 0.83-1.54). CONCLUSION: After
      esophagectomy, the site of anastomosis does not predict an increased risk of
      perioperative morbidity or mortality.

PMID- 24108569
TI  - Dynamic contrast-enhanced MRI of nasopharyngeal carcinoma: a preliminary study of
      the correlations between quantitative parameters and clinical stage.
AB  - PURPOSE: To evaluate the relationship between quantitative parameters of dynamic
      contrast-enhanced magnetic resonance imaging (DCE-MRI) and clinical stage of
      nasopharyngeal carcinoma (NPC). MATERIALS AND METHODS: Fifty-one newly diagnosed
      NPC patients received MRI examination on Philips Achieva 3.0 Tesla TX MR system.
      We used DCE-Tool (Philips Healthcare, Best, The Netherlands) to investigate
      parameters from primary tumors. Tumor/node/metastasis and corresponding clinical
      stages were determined based on 2009 UICC 7th edition. The correlations between
      quantitative parameters and clinical stage were correlated using Pearson
      correlation analysis. RESULTS: Mean K(trans) , Kep , ve , and vp for primary
      tumors were 0.500 +/- 0.188/min, 0.744 +/- 0.273/min, 0.986 +/- 0.595, and 0.052
      +/- 0.071, respectively. Both K(trans) and Kep of tumors showed moderate negative
      correlation with clinical stage, T stage and N stage (P < 0.05), while ve showed
      moderate positive correlation with them (P < 0.05). vp revealed a moderate
      negative correlation with T stage (r = -0.369; P < 0.004). Kep and ve have
      significant differences between many early and advanced stages patients.
      CONCLUSION: DCE-MRI is feasible to assess vascular permeability of NPC patients.
      Our results first revealed that the quantitative parameters were significantly
      related to clinical stage of NPC. Thus, DCE-MRI may be valuable to add
      noninvasive prognostic indicators in evaluating NPC.

PMID- 24108570
TI  - Summer migrant students learn healthy choices through videography.
AB  - The purpose of this single-group pre- and posttest intervention pilot study was
      to teach middle school migrant farmworker children the benefits of healthy eating
      and activity using a multimedia and ethnic-tailored health curriculum, embedded
      in a 7-week summer Migrant Education Program. Conceptual frameworks were from
      transcultural nursing, education, and child development. Student-made video
      productions enhanced classroom learning and content retention. Outcomes were
      health infomercials, body mass index (BMI), BMI percentile, muscle strength and
      flexibility, and We Can! and Coordinated Approach To Child Health (CATCH)
      surveys. Sixty-four students were enrolled (girls n = 31, boys n = 33), 96%
      Latino, and 65% were overweight or obese. Students had significant improvement in
      12 knowledge and attitudes measures with significant gender differences in 11
      measures. Although not statistically significant, trends toward healthier weight
      were seen. Five student infomercials were produced. The school environment
      effectively delivered health promotion to migrant children and will serve as a
      prototype for middle school health interventions. 

PMID- 24108571
TI  - Real-time in situ powder X-ray diffraction monitoring of mechanochemical
      synthesis of pharmaceutical cocrystals.
AB  - Looking in: The penetrating power of high-energy X-rays provides a means to
      monitor in situ and in real time the course of ball-milling reactions of organic
      pharmaceutical solids by detecting crystalline phases and assessing the evolution
      of their particle sizes. Upon switching from neat grinding to liquid-assisted
      grinding, cocrystal formation is enabled or tremendously accelerated, while the
      reaction mechanism alters its course. 

PMID- 24108572
TI  - Depth-dependent refractive index of normal and early degenerated articular
      cartilage.
AB  - The depth distributions of refractive index (RI) in normal and early degenerated
      articular cartilage (AC) were measured and correlated to the pathological
      statuses. Utilizing a confocal microscope, the depth distribution of RI was
      determined with an interval of 50 MUm from the articular surface and approximated
      as a smooth curve. The fluctuation of RI was quantified with a specially defined
      coefficient and the proteoglycan (PG) loss was quantified with histological
      images. The overall RI of the AC collected from the femoral condyles of mature
      sheep was 1.4444. Significant differences existed in the refractive indices of
      different cartilage samples or even in the different depths of the same sample.
      The RI of normal cartilage distributed as a regular ramp or arch curve with depth
      and peaked in the middle-deep zone. The cartilage samples detected with high PG
      losses were coupled with severe fluctuations of RI. The fluctuating level was
      increased with pathological progress. The coefficient of RI fluctuation can
      distinguish the normal cartilage from the initially degenerated one, which
      potentially provides an indicator to detect the pathological development of AC.

PMID- 24108573
TI  - Multimodal tissue imaging: using coregistered optical tomography data to estimate
      tissue autofluorescence intensity change due to scattering and absorption by
      neoplastic epithelial cells.
AB  - Autofluorescence (AF) imaging provides valuable information about the structural
      and chemical states of tissue that can be used for early cancer detection.
      Optical scattering and absorption of excitation and emission light by the
      epithelium can significantly affect observed tissue AF intensity. Determining the
      effect of epithelial attenuation on the AF intensity could lead to a more
      accurate interpretation of AF intensity. We propose to use optical coherence
      tomography coregistered with AF imaging to characterize the AF attenuation due to
      the epithelium. We present imaging results from three vital tissue models, each
      consisting of a three-dimensional tissue culture grown from one of three
      epithelial cell lines (HCT116, OVCAR8, and MCF7) and immobilized on a
      fluorescence substrate. The AF loss profiles in the tissue layer show two
      different regimes, each approximately linearly decreasing with thickness. For
      thin cell cultures (<300 MUm), the AF signal changes as AF(t)/AF(0)=1-1.3t (t is
      the thickness in millimeter). For thick cell cultures (>400 MUm), the AF loss
      profiles have different intercepts but similar slopes. The data presented here
      can be used to estimate AF loss due to a change in the epithelial layer thickness
      and potentially to reduce AF bronchoscopy false positives due to inflammation and
      non-neoplastic epithelial thickening.

PMID- 24108574
TI  - Monte Carlo simulation of light transport in tissue for optimizing light delivery
      in photoacoustic imaging of the sentinel lymph node.
AB  - Noninvasive or minimally invasive identification of sentinel lymph node (SLN) is
      essential to reduce the surgical effects of SLN biopsy. Photoacoustic (PA)
      imaging of SLN in animal models has shown its promise for clinical use in the
      future. Here, we present a Monte Carlo simulation for light transport in the SLN
      for various light delivery configurations with a clinical ultrasound probe. Our
      simulation assumes a realistic tissue layer model and also can handle the
      transmission/reflectance at SLN-tissue boundary due to the mismatch of refractive
      index. Various light incidence angles show that for deeply situated SLNs the
      maximum absorption of light in the SLN is for normal incidence. We also show that
      if a part of the diffused reflected photons is reflected back into the skin using
      a reflector, the absorption of light in the SLN can be increased significantly to
      enhance the PA signal.

PMID- 24108575
TI  - Novel shifts in memory research and their impact on the legal process:
      introduction to the special issue on memory formation and suggestibility in the
      legal process.
AB  - The functioning and frailties of memory are frequently at the centerpiece of much
      expert testimony about the reliability of eyewitness accounts. Although we have
      much knowledge about how false memories and suggestibility can affect
      testimonies, the contributions in this special issue show that when using a sound
      theoretical framework, novel directions in this field can surface. The papers in
      this issue can broadly be divided into contributions that are related to: (1) the
      exact determinants of false memory and suggestibility; (2) new paradigms in legal
      psychology; (3) positive consequences of memory illusions; and (4) developmental
      false memory research. Collectively, these contributions have the potential to
      provide novel shifts in memory research and push this field beyond its current
      boundaries.

PMID- 24108576
TI  - The effect of expertise on memory conformity: a test of informational influence.
AB  - Conforming to erroneous memory reports of co-witnesses can have serious impacts
      on subsequent forensic investigation and court reports. One theoretical
      explanation proposed is that memory conformity arises due to informational
      influence; the co-witness desires to give accurate information and reports the co
      witness's version because they perceive the co-witness as being more credible. We
      tested the idea that perceptions of credibility drive memory conformity. We
      manipulated credibility through expertise; specifically, by telling participants
      that the (confederate) co-witness had previously worked as either a policeman
      (high expertise) or an electrician (low expertise). After a discussion with the
      co-witness, we assessed cued-recall memory and perceptions of credibility about
      the co-witness and the self. We found that higher expertise led to greater memory
      conformity. Although higher expertise also led to higher credibility assessments
      of the co-witness, this was only for perceptions of the credibility as an eye
      witness and memory confidence, neither of which predicted memory conformity. By
      contrast, memory accuracy of the co-witness relative to self-memory accuracy
      predicted memory conformity, but this was not affected by expertise. These
      results show support for an informational influence explanation but suggest that
      expertise perceptions operate differently from our explanation.

PMID- 24108577
TI  - Renal medullary carcinoma in an adolescent with sickle cell anemia.

PMID- 24108578
TI  - Redox-responsive self-healing for corrosion protection.
AB  - Raspberry-shaped redox-responsive capsules for storing corrosion inhibitors are
      introduced, targeted to solve the drawbacks of conducting-polymer-based coating
      systems for corrosion protection. These capsules synthesized via the miniemulsion
      technique have a remarkable release property upon reduction (onset of corrosion)
      and cease release upon reoxidation (passivation of the defect). The self-healing
      capability is demonstrated by application of these capsules as part of a
      composite coating on zinc. 

PMID- 24108579
TI  - Extracellular haemoglobin upregulates and binds to tissue factor on macrophages:
      implications for coagulation and oxidative stress.
AB  - The mechanisms of crosstalk between haemolysis, coagulation and innate immunity
      are evolutionarily conserved from the invertebrate haemocyanin to the vertebrate
      haemoglobin (Hb). In vertebrates, extracellular Hb resulting from haemolytic
      infections binds bacterial lipopolysaccharide (LPS) to unleash the antimicrobial
      redox activity of Hb. Because bacterial invasion also upregulates tissue factor
      (TF), the vertebrate coagulation initiator, we asked whether there may be
      functional interplay between the redox activity of Hb and the procoagulant
      activity of TF. Using real-time PCR, TF-specific ELISA, flow cytometry and TF
      activity assay, we found that Hb upregulated the expression of functional TF in
      macrophages. ELISA, flow cytometry and immunofluorescence microscopy showed
      binding between Hb and TF, in isolation and in situ. Bioinformatic analysis of Hb
      and TF protein sequences showed co-evolution across species, suggesting that
      Hbbeta binds TF. Empirically, TF suppressed the LPS-induced activation of Hb
      redox activity. Furthermore, Hb desensitised TF to the effects of antioxidants
      like glutathione or serum. This bi-directional regulation between Hb and TF
      constitutes a novel link between coagulation and innate immunity. In addition,
      induction of TF by Hb is a potentially central mechanism for haemolysis to
      trigger coagulation. 

PMID- 24108580
TI  - Influence of patient, physician, and hospital factors on 30-day readmission
      following pancreatoduodenectomy in the United States.
AB  - IMPORTANCE It is not known whether hospital and surgeon volumes have an
      association with readmission among patients undergoing pancreatoduodenectomy.
      OBJECTIVE: To evaluate patient-, surgeon-, and hospital-level factors associated
      with readmission. DESIGN, SETTING, AND PARTICIPANTS: Retrospective cohort study
      using the Surveillance, Epidemiology, and End Results (SEER)-Medicare data with
      cases diagnosed from January 1, 1998, to December 31, 2005, and followed up until
      December 2007. Population-based cancer registry data were linked to Medicare data
      for the corresponding patients. A total of 1488 unique individuals who underwent
      a pancreatoduodenectomy were identified. INTERVENTIONS: Undergoing
      pancreatoduodenectomy at hospitals classified by volume of pancreatoduodenectomy
      procedures performed at the facility were either very-low, low, medium, or high
      volume. Undergoing pancreatoduodenectomy by surgeons classified by volume of
      pancreatoduodenectomy procedures performed by the surgeon were either very-low,
      low, medium, or high volume. MAIN OUTCOMES AND MEASURES: In-hospital morbidity,
      mortality, and 30-day readmission were examined. RESULTS: The median age was 74
      years, and 1436 patients (96.5%) had a least 1 medical comorbidity. Patients were
      treated by 575 distinct surgeons at 298 distinct hospitals. Length of stay was
      longest (median, 17 days) and 90-day mortality highest (17.2%) at very-low-volume
      hospitals (P < .001). Among all pancreatoduodenectomy patients, 292 (21.3%) were
      readmitted within 30 days of discharge. There was no effect of surgeon volume and
      a modest effect of hospital volume (odds ratio for highest- vs lowest-volume
      quartiles, 1.85; 95% CI, 1.22-2.80; P = .02). The presence of significant
      preoperative medical comorbidities was associated with an increased risk for
      hospital readmission after pancreatoduodenectomy. A comorbidity score greater
      than 13 had a pronounced effect on the chance of readmission following
      pancreatoduodenectomy (odds ratio, 2.06; 95% CI, 1.56-2.71; P < .001). The source
      of variation in readmission was primarily attributable to patient-related factors
      (95.4%), while hospital factors accounted for 4.3% of the variability and
      physician factors for only 0.3%. CONCLUSIONS AND RELEVANCE: Nearly 1 in 5
      patients are readmitted following pancreatoduodenectomy. While variation in
      readmission is, in part, attributable to differences among hospitals, the largest
      share of variation was found at the patient level.

PMID- 24108582
TI  - Molecular component distribution imaging of living cells by multivariate curve
      resolution analysis of space-resolved Raman spectra.
AB  - Label-free Raman microspectroscopy combined with a multivariate curve resolution
      (MCR) analysis can be a powerful tool for studying a wide range of biomedical
      molecular systems. The MCR with the alternating least squares (MCR-ALS)
      technique, which retrieves the pure component spectra from complicatedly
      overlapped spectra, has been successfully applied to in vivo and molecular-level
      analysis of living cells. The principles of the MCR-ALS analysis are reviewed
      with a model system of titanium oxide crystal polymorphs, followed by two
      examples of in vivo Raman imaging studies of living yeast cells, fission yeast,
      and budding yeast. Due to the non-negative matrix factorization algorithm used in
      the MCR-ALS analysis, the spectral information derived from this technique is
      just ready for physical and/or chemical interpretations. The corresponding
      concentration profiles provide the molecular component distribution images
      (MCDIs) that are vitally important for elucidating life at the molecular level,
      as stated by Schroedinger in his famous book, "What is life?" Without any a
      priori knowledge about spectral profiles, time- and space-resolved Raman
      measurements of a dividing fission yeast cell with the MCR-ALS elucidate the
      dynamic changes of major cellular components (lipids, proteins, and
      polysaccharides) during the cell cycle. The MCR-ALS technique also resolves
      broadly overlapped OH stretch Raman bands of water, clearly indicating the
      existence of organelle-specific water structures in a living budding yeast cell.

PMID- 24108581
TI  - Clinical experience with insulin detemir in patients with type 2 diabetes from
      the near East countries.
AB  - INTRODUCTION: This study aimed at determining the clinical safety and efficacy of
      insulin detemir (IDet) in combination with oral anti-diabetic drugs (OADs) in
      type 2 diabetes (T2D) patients from four Near East Countries (Israel, Jordan,
      Pakistan and Lebanon). METHODS: This prospective observational study included T2D
      patients previously on OADs and newly diagnosed patients initiating IDet with or
      without OADs, at the discretion of physicians. Safety objectives included
      evaluation of hypoglycemia and adverse drug reactions (ADRs) from baseline to
      Week 24. Efficacy outcomes included baseline to Week 24 changes in glucose
      control parameters (glycated hemoglobin [HbA1c], fasting plasma glucose [FPG] and
      post-breakfast post-prandial plasma glucose [PPPG]). Change in body weight during
      this period was also assessed. RESULTS: A total of 2,155 patients (mean +/- SD:
      age 57.1 +/- 11.0 years, BMI 29.4 +/- 5.1 kg/m(2), average diabetes duration 9.2
      +/- 5.4 years) were included. IDet dose at baseline was 0.20 +/- 0.09 U/kg
      titrated up to 0.34 +/- 0.14 U/kg by Week 24. From baseline to Week 24, the total
      number of hypoglycemic episodes increased from 1.30 to 1.37 events/patient-year,
      while major hypoglycemic episodes decreased from 0.15 to 0.02 events/patient
      year. A total of 9 ADRs were reported, of which one event was a serious ADR.
      Statistically significant improvements in glucose control were reported from
      baseline to Week 24 (HbA1c: 9.6 +/- 1.6% vs. 7.6 +/- 1.1%; FPG: 201.5 +/- 59.5
      mg/dL vs. 124.9 +/- 31.6 mg/dL; PPPG: 264.2 +/- 65.7 mg/dL vs. 167.2 +/- 36.8
      mg/dL; all p < 0.0001). Body weight did not change significantly after 24 weeks
      of IDet therapy. CONCLUSION: IDet therapy in combination with OADs improved
      glycemic control without increasing the risk of hypoglycemia or weight gain.

PMID- 24108583
TI  - Loss-of-function mutation in the NOTCH3 gene: simply a polymorphism?

PMID- 24108584
TI  - Mechanical and biological properties of chitosan/carbon nanotube nanocomposite
      films.
AB  - In this article, different concentrations of multiwalled carbon nanotube (MWCNT)
      were homogeneously dispersed throughout the chitosan (CS) matrix. A simple
      solvent-cast method was used to fabricate chitosan films with 0.1, 0.5, and 1% of
      MWCNT with the average diameter around 30 nm. The CS/MWCNT films were
      characterized for structural, viscous and mechanical properties with optical
      microscopy, wide-angle X-ray diffraction, Raman spectroscopy, tensile test
      machine, and microindentation testing machine. Murine osteoblasts were used to
      examine the cell viability and attachment of the nanocomposite films at two time
      points. In comparison to the pure chitosan film, the mechanical properties,
      including the tensile modulus and strength of the films, were greatly improved by
      increasing the percentage of MWCNT. Furthermore, adding MWCNT up to 1% increased
      the viscosity of the chitosan solution by 15%. However, adding MWCNT decreased
      the samples ductility and transparency. In biological point of view, no toxic
      effect on osteoblasts was observed in the presence of different percentages of
      MWCNT at day 3 and day 7. This investigation suggested MWCNT could be a promising
      candidate for improving chitosan mechanical properties without inducing
      remarkable cytotoxicity on bone cells.

PMID- 24108585
TI  - An orders-of-magnitude increase in the rate of the solid-catalyzed CO oxidation
      by in situ ball milling.

PMID- 24108586
TI  - Systemic rheumatoid vasculitis in the era of modern immunosuppressive therapy.
AB  - OBJECTIVES: Systemic rheumatoid vasculitis (SRV) is a rare but potentially
      serious systemic disease manifestation of rheumatoid arthritis (RA) characterized
      by the development of necrotizing vasculitis. The incidence of SRV appears to be
      decreasing possibly reflecting progress in RA treatment. The aims of this study
      were to review the clinical manifestations of SRV in a stable well-defined
      population during 2001-10 and to compare with our previous cohort (1988-2000) and
      also a cohort from 1975 to 1981. METHODS: Using Norfolk Vasculitis Register, a
      prospective register of patients with systemic vasculitis since 1988, all
      patients with a diagnosis of SRV from 1 January 2001 until 31 December 2010 were
      identified. SRV was defined according to the Scott and Bacon criteria (1984).
      Clinical features were obtained by retrospective case note review. RESULTS:
      Eighteen patients with SRV were identified (10 male), median age at diagnosis was
      72 years and average disease duration 15.6 years. The average annual incidence
      for 2001-10 was 3.9 per million. One-year mortality was 12% and 5-year mortality
      60%. The clinical manifestations were similar apart from systemic and cutaneous
      features which were more common in the earlier cohorts. CONCLUSION: The incidence
      of SRV has declined significantly in the last 40 years; but the clinical
      manifestations remain similar. Systemic symptoms, and cutaneous manifestations
      such as infarcts and nodules, are slightly less common in the recent cohort.
      Despite modern immunosuppressive therapy the prognosis remains poor.

PMID- 24108589
TI  - Asymmetric C(sp(2) )-H activation.
AB  - A "niche" topic in the past decade, the asymmetric C-H bond activation has been
      attracting growing interest over the last few years. Particularly significant
      advances have been achieved in the field of direct, stereoselective
      transformations of C(sp(2) )-H bonds. This Concept article intends to showcase
      different types of asymmetric C(sp(2) )-H bond activation reactions, emphasising
      both the nature of the stereo-discriminating step and the variability of valuable
      scaffolds that could be rapidly constructed by means of such strategies.

PMID- 24108590
TI  - Formation of a covalent glycosyl-enzyme species in a retaining
      glycosyltransferase.
AB  - Elusive glycosyl-enzyme adduct: Using classical MD simulations and QM/MM
      metadynamics, the long-time sought glycosyl-enzyme covalent intermediate of a
      retaining glycosyltransferase, with a putative nucleophile residue in the active
      site, has been trapped (MD=molecular dynamics; QM/MM=quantum mechanics/molecular
      mechanics). 

PMID- 24108591
TI  - Stabilisation of carbon-supported palladium nanoparticles through the formation
      of an alloy with gold: application to the Sonogashira reaction.
AB  - Oh my Gold! Gold atoms stabilise catalytically active palladium nanoparticles
      when engaged in an alloy heterogenised on carbon. The increased durability makes
      the Pd-Au/C catalyst more recyclable than the gold-free Pd/C catalyst for the
      Sonogashira reaction. 

PMID- 24108592
TI  - Direct use of methanol as an alternative to formaldehyde for the synthesis of
      3,3'-bisindolylmethanes (3,3'-BIMs).
AB  - Red card for formaldehyde: The direct coupling of indoles with methanol to 3,3'
      bisindolylmethanes with good to excellent yields was accomplished by using a
      commercially available iridium complex. This study demonstrates the potential of
      direct use of methanol as an alternative to formaldehyde for synthetic
      transformations. 

PMID- 24108593
TI  - Gold(I)-catalyzed protodecarboxylation of (hetero)aromatic carboxylic acids.
AB  - Golden delivery: A gold(I)-NHC complex catalyses the protodecarboxylation of
      various (hetero)aromatic acids. This methodology is simple, highly efficient and
      combines both the advantages of copper and silver methods with applications to
      completely deactivated substrates. Moreover, intermediates in this reaction have
      been isolated and fully characterized and provide fundamental insights into the
      mechanism of protodecarboxylation with gold. 

PMID- 24108594
TI  - Visible-light-induced trifluoromethylation of N-aryl acrylamides: a convenient
      and effective method to synthesize CF(3)-containing oxindoles bearing a
      quaternary carbon center.
AB  - Trifluoromethylation/arylation: N-aryl acrylamides undergo visible-light-induced
      tandem trifluoromethylation/arylation in the presence of a ruthenium
      photocatalyst with Togni's reagent as the CF3 source. This reaction serves as a
      powerful and ecofriendly synthetic method for the preparation of a variety of CF3
      -containing oxindoles bearing a quaternary carbon center. 

PMID- 24108595
TI  - Copper-catalyzed trifluoromethyl thiolation--mild and efficient synthesis of
      trifluoromethyl thioethers.
AB  - Mild-mannered sulfur: A general method for the synthesis of vinyl trifluoromethyl
      thioethers starting from readily available di-, tri-, and tetrasubstituted vinyl
      iodides was developed. A wide variety of substrates were applied in the reaction
      with CuSCF3 to give the corresponding products in high yields, within short
      reaction times, with retention of the initial E/Z isomer ratio. In addition, a
      copper-catalyzed trifluoromethyl thioether protocol has been also developed. 

PMID- 24108596
TI  - beta-Type glycosidic bond formation by palladium-catalyzed decarboxylative
      allylation.
AB  - Decarboxylative allylation of glycals: A beta-type glycosidic bond has been
      constructed in high regio- and stereoselectivity by means of a palladium
      catalyzed decarboxylative O-glycosylation. Various kinds of glycals with
      different protecting groups have been examined for this reaction to afford a
      diverse set of glycosylated products, including phenolic O-glycosides,
      thiophenolic S-glycoside, aliphatic O-glycosides, and disaccharides with
      excellent beta-selectivity and reasonable to excellent yields. 

PMID- 24108597
TI  - Synthesis and transistor properties of asymmetric oligothiophenes: relationship
      between molecular structure and device performance.
AB  - A series of three thiophene-naphthalene-based asymmetric oligomers-5-decyl
      2,2':5',2'':5'',2'''-quaterthiophene (DtT), 5-decyl-5''-(naphthalen-2-yl)
      2,2':5',2''-terthiophene (D3TN), and 5-(4-decylphenyl)-5'-(naphthalen-2-yl)-2,2'
      bithiophene (DP2TN)-was synthesized by Suzuki cross-coupling reactions. The long
      alkyl side chains improved both the solubility of the oligomers in solvents and
      their tendency to self-assemble. UV/Vis absorption measurements suggested that
      DtT, D3TN, and DP2TN form H-type aggregates with a face-to-face packing
      structure. In addition, the three oligomers were found to adopt vertically
      aligned crystalline structures in films deposited on substrates, as revealed by
      grazing-incidence wide-angle X-ray scattering. These oligomers were used as the
      active layers of p-type organic field-effect transistors, and the resulting
      devices showed field-effect mobilities of 3.3*10(-3)  cm(2)  V(-1)  s(-1) for
      DtT, 1.6*10(-2)  cm(2)  V(-1)  s(-1) for D3TN, and 3.7*10(-2)  cm(2)  V(-1)  s(
      1) for DP2TN. The differences in transistor performances were attributed to the
      degree of pi overlap and the morphological differences determined by the
      molecular structures. 

PMID- 24108598
TI  - Size- and orientation-selective encapsulation of C(70) by cycloparaphenylenes.
AB  - The size- and orientation-selective formation of the shortest-possible C70 peapod
      in solution and in the solid state by using the shortest structural unit of an
      "armchair" carbon nanotube (CNT), cycloparaphenylene (CPP), has been studied.
      [10]CPP and [11]CPP exothermically formed 1:1 complexes with C70 , thereby giving
      the resulting peapods. A van't Hoff plot analysis revealed that the formation of
      these complexes in 1,2-dichlorobenzene was mainly driven by entropy, whereas the
      theoretical calculations suggested that the formation of the complex in the gas
      phase was predominantly driven by enthalpy. C70 was found to exist in two
      distinct orientations inside the CPP cavity, namely "lying" and "standing",
      depending on the specific size of the CPP. The theoretical calculations and the X
      ray crystallographic analysis revealed that the interactions between [10]CPP and
      the short axis of C70 in its lying orientation were isotropic and similar to
      those observed between [10]CPP and C60 . However, the interactions between
      [11]CPP and C70 in its standing orientation were anisotropic, thereby involving
      the radial deformation of [11]CPP into an ellipsoidal shape. This "induced fit"
      maximized the van der Waals interactions with the long axis of C70 . Theoretical
      calculations revealed that the deformation occurred readily with low energy loss,
      thus suggesting that CPPs are highly radially elastic molecules. These results
      also indicate that the same type of radial deformation should occur in CNT
      peapods that encapsulate anisotropic fullerenes. 

PMID- 24108599
TI  - Cyclometalated ruthenium(II) complexes featuring tridentate click-derived ligands
      for dye-sensitized solar cell applications.
AB  - A series of heteroleptic bis(tridentate) Ru(II) complexes featuring N^C^N
      cyclometalating ligands is presented. The 1,2,3-triazole-containing tridentate
      ligands are readily functionalized with hydrophobic side chains by means of click
      chemistry and the corresponding cyclometalated Ru(II) complexes are easily
      synthesized. The performance of these thiocyanate-free complexes in a dye
      sensitized solar cell was tested and a power conversion efficiency (PCE) of up to
      4.0 % (Jsc =8.1 mA cm(-2) , Voc =0.66 V, FF=0.70) was achieved, while the black
      dye ((NBu4 )3 [Ru(Htctpy)(NCS)3 ]; Htctpy=2,2':6',2''-terpyridine-4'-carboxylic
      acid-4,4''-dicarboxylate) showed 5.2 % (Jsc =10.7 mA cm(-2) , Voc =0.69 V,
      FF=0.69) under comparable conditions. When co-adsorbed with chenodeoxycholic
      acid, the PCE of the best cyclometalated dye could be improved to 4.5 % (Jsc =9.4
      mA cm(-2) , Voc =0.65 V, FF=0.70). The PCEs correlate well with the light
      harvesting capabilities of the dyes, while a comparable incident photon-to
      current efficiency was achieved with the cyclometalated dye and the black dye.
      Regeneration appeared to be efficient in the parent dye, despite the high energy
      of the highest occupied molecular orbital. The device performance was
      investigated in more detail by electrochemical impedance spectroscopy.
      Ultimately, a promising Ru(II) sensitizer platform is presented that features a
      highly functionalizable "click"-derived cyclometalating ligand. 

PMID- 24108600
TI  - Transcriptome dynamics of transgene amplification in Chinese hamster ovary cells.
AB  - Dihydrofolate reductase (DHFR) system is used to amplify the product gene to
      multiple copies in Chinese Hamster Ovary (CHO) cells for generating cell lines
      which produce the recombinant protein at high levels. The physiological changes
      accompanying the transformation of the non-protein secreting host cells to a high
      producing cell line is not well characterized. We performed transcriptome
      analysis on CHO cells undergoing the selection and amplification processes. A
      host CHO cell line was transfected with a vector containing genes encoding the
      mouse DHFR (mDHFR) and a recombinant human IgG (hIgG). Clones were isolated
      following selection and subcloned following amplification. Control cells were
      transfected with a control plasmid which did not have the hIgG genes. Although
      methotrexate (MTX) amplification increased the transcript level of the mDHFR gene
      significantly, its effect on both hIgG heavy and light chain genes was more
      modest. The subclones appeared to retain the transcriptome signatures of their
      parental clones, however, their productivity varied among those derived from the
      same clone. The transcript levels of hIgG transgenes of all subclones fall in a
      narrower range than the product titer, alluding to the role of many functional
      attributes, other than transgene transcript, on productivity. We cross examined
      functional class enrichment during selection and amplification as well as between
      high and low producers and discerned common features among them. We hypothesize
      that the role of amplification is not merely increasing transcript levels, but
      also enriching survivors which have developed the cellular machinery for
      secreting proteins, leading to an increased frequency of isolating high-producing
      clones. We put forward the possibility of assembling a hyper-productivity gene
      set through comparative transcriptome analysis of a wide range of samples.

PMID- 24108601
TI  - A novel natural mutation AalphaPhe98Ile in the fibrinogen coiled-coil affects
      fibrinogen function.
AB  - The aim of this study was to investigate the structure and function of fibrinogen
      obtained from a patient with normal coagulation times and idiopathic
      thrombophilia. This was done by SDS-PAGE and DNA sequence analyses, scanning
      electron microscopy, fibrinopeptide release, fibrin polymerisation initiated by
      thrombin and reptilase, fibrinolysis, and platelet aggregometry. A novel
      heterozygous point mutation in the fibrinogen Aalpha chain, Phe98 to Ile, was
      found and designated as fibrinogen Vizovice. The mutation, which is located in
      the RGDF sequence (Aalpha 95-98) of the fibrinogen coiled-coil region,
      significantly affected fibrin clot morphology. Namely, the clot formed by
      fibrinogen Vizovice contained thinner and curled fibrin fibers with reduced
      length. Lysis of the clots prepared from Vizovice plasma and isolated fibrinogen
      were found to be impaired. The lysis rate of Vizovice clots was almost four times
      slower than the lysis rate of control clots. In the presence of platelets
      agonists the mutant fibrinogen caused increased platelet aggregation. The data
      obtained show that natural mutation of Phe98 to Ile in the fibrinogen Aalpha
      chain influences lateral aggregation of fibrin protofibrils, fibrinolysis, and
      platelet aggregation. They also suggest that delayed fibrinolysis, together with
      the abnormal fibrin network morphology and increased platelet aggregation, may be
      the direct cause of thrombotic complications in the patient associated with
      pregnancy loss. 

PMID- 24108602
TI  - Efficacy of antibacterial bioactive glass S53P4 against S. aureus biofilms grown
      on titanium discs in vitro.
AB  - We evaluated the effectiveness of different sizes of bioactive glass S53P4
      against Staphylococcus aureus biofilms grown on metal discs in vitro. S. aureus
      biofilms were cultivated on titanium discs. BAG-S53P4 (0.5-0.8 mm and <45 um)
      were placed in contact with the discs containing biofilms. Glass beads (0.5 mm)
      were used as a control. After each interval, the pH from each sample was
      measured. Colony forming units were counted for the biofilm recovery
      verification. In parallel, we tested the activity of bioactive glass against S.
      aureus planktonic cells. We found that BAG-S53P4 can suppress S. aureus biofilm
      formation on titanium discs in vitro. The suppression rate of biofilm cells by
      BAG-S53P4 <45 um was significantly higher than by BAG-S53P4 0.5-0.8 mm. BAG-S53P4
      has a clear growth-inhibitory effect on S. aureus biofilms. BAG-S53P4 <45 um is
      more efficient against biofilm growth in vitro comparing with BAG-S53P4 0.5-0.8
      mm. Bioactive glass S53P4 has potential to be used as bone substitute for the
      resolution of infection complications in joint replacement surgeries and
      treatment of chronic osteomyelitis.

PMID- 24108603
TI  - Utility of specimens positive for Neisseria gonorrhoeae by the Aptima Combo 2
      assay for assessment of strain diversity and antibiotic resistance.
AB  - In our jurisdiction, the Aptima Combo 2 assay (Gen-Probe, Inc.) is used to detect
      Neisseria gonorrhoeae from specimens collected at clinics for sexually
      transmitted infections (STI) and from select community patients. In addition,
      swabs are also collected for N. gonorrhoeae culture, susceptibility testing, and
      sequence typing (ST). Since only a small proportion of samples from provincial
      cases undergo culture, the available trends in antimicrobial susceptibility and
      predominant strain types may not be representative of all N. gonorrhoeae
      infections. Due to the limitations facing the use of N. gonorrhoeae culture to
      understand these trends in the general community, we performed a molecular
      analysis for markers of cephalosporin resistance and ST determination by using
      nucleic acid extracts of specimens sent for Aptima testing. Thirty-four samples
      submitted for both Aptima testing and N. gonorrhoeae culture from the same
      anatomic location (within 24 h) were included in the study. Sequence type was
      determined based on the sequence of the por and tbpB genes, and amino acid
      changes in the PBP 2 protein, encoded by the penA gene, were considered
      representative for the assessment of antimicrobial susceptibility. Sequence
      identity of 100% was observed between the sequences obtained from Aptima-analyzed
      samples and culture samples. Sequencing results showed an association between
      decreased susceptibility to extended-spectrum cephalosporins (ESC(ds)), tbp
      allele 110, ST 1407, and amino acid changes (G545S, I312M, and V316T) in the PBP
      2 protein. Our data, generated based on a few representative genes, suggest that
      gonococcal samples positive by Aptima testing can be used to determine single
      nucleotide polymorphisms associated with ESC(ds) and the sequence type based on
      molecular strain typing. Confirmation of these findings may obviate the need for
      gonorrhea culture in the future. 

PMID- 24108604
TI  - Sensitivity, specificity, and reproducibility of the Capilia TB-Neo assay.
AB  - The performance of the Capilia TB-Neo assay, a new-generation assay, was assessed
      by determining its sensitivity, specificity, reproducibility, and cross-reaction
      with contaminating organisms. The sensitivity and specificity were 99.2 and 96.4%
      and 89.3 and 100% in pure and mixed-culture isolates, respectively. The kappa
      statistic was 95.0 and 77.9% in pure and mixed culture isolates, respectively.
      There was no cross-reaction with contaminating organisms. 

PMID- 24108605
TI  - Extraintestinal pathogenic Escherichia coli carrying the Shiga Toxin gene stx2.

PMID- 24108606
TI  - Consistency of influenza A virus detection test results across respiratory
      specimen collection methods using real-time reverse transcription-PCR.
AB  - In our prospective cohort study, we compared the performance of nasopharyngeal,
      oropharyngeal, and nasal swabs for the detection of influenza virus using real
      time reverse transcription-PCR assay. Joint consideration of results from
      oropharyngeal and nasal swabs was as effective as consideration of results from
      nasopharyngeal swabs alone, as measured by sensitivity and noninferiority
      analysis. 

PMID- 24108607
TI  - Molecular diagnosis of Actinomadura madurae infection by 16S rRNA deep
      sequencing.
AB  - Next-generation DNA sequencing can be used to catalog individual organisms within
      complex, polymicrobial specimens. Here, we utilized deep sequencing of 16S rRNA
      to implicate Actinomadura madurae as the cause of mycetoma in a diabetic patient
      when culture and conventional molecular methods were overwhelmed by overgrowth of
      other organisms. 

PMID- 24108608
TI  - Temporal and spatial compartmentalization of drug-resistant cytomegalovirus (CMV)
      in a child with CMV meningoencephalitis: implications for sampling in molecular
      diagnosis.
AB  - We describe a case of antiviral-resistant cytomegalovirus meningoencephalitis
      occurring after hematopoietic stem cell transplantation. Antiviral-resistant
      cytomegalovirus was identified in blood 16 months earlier. However, wild-type
      cytomegalovirus was evidenced in blood when the meningoencephalitis was
      diagnosed. Treatment of meningoencephalitis should be adapted to all previously
      identified resistance mutations in any compartment. 

PMID- 24108609
TI  - Clinical evaluation of BacT/Alert FA plus and FN plus bottles compared with
      standard bottles.
AB  - The performance of the BacT/Alert FA Plus and FN Plus resin bottles was evaluated
      in comparison with that of standard aerobic (SA) and standard anaerobic (SN)
      bottles. Twenty milliliters of blood from adult patients was equally distributed
      into four types of bottles: FA Plus, FN Plus, SA, and SN. The detection of
      clinically significant organisms and the time to detection (TTD) were monitored
      for each bottle. Among the 3,103 blood culture sets that were requested, the
      blood volume of each bottle was over 4 ml in 1,481 sets (47.7%). Among these
      1,481 sets, 158 cultures grew in the FA Plus and SA bottles, and 136 grew in the
      FN Plus and SN bottles. Growth in only one type of bottle was more commonly
      observed for the FA Plus (n = 38) than for the SA (n = 14) (P = 0.001) bottles
      and for the FN Plus (n = 27) than for the SN (n = 10) (P = 0.008) bottles. Gram
      negative bacilli were more frequently isolated in the resin bottles (P < 0.05).
      The skin contamination rate was 1.2% in the resin bottles and the standard
      bottles. The mean TTD was 11.1 h in the FA Plus bottles versus 13.1 h in the SA
      bottles (P < 0.001) and 12.0 h in the FN Plus bottles versus 12.8 h in the SN
      bottles (P = 0.083). Clinically significant bacteria, including Gram-negative
      bacilli, were isolated more frequently from the resin bottles than from the
      standard bottles. Clinically significant bacteria were detected faster using the
      aerobic resin bottles than using the standard aerobic bottles. This finding might
      not be applicable to the standard-practice 10-ml protocol for each bottle because
      the results from using a smaller volume (5 ml) might be less pronounced. 

PMID- 24108610
TI  - Exploring alternative biomaterials for diagnosis of pulmonary tuberculosis in HIV
      negative patients by use of the GeneXpert MTB/RIF assay.
AB  - The utility of the GeneXpert MTB/RIF (Xpert) assay for detection of Mycobacterium
      tuberculosis in sputum samples has been extensively studied. However, the
      performance of the Xpert assay as applied to other readily accessible body fluids
      such as exhaled breath condensate (EBC), saliva, urine, and blood has not been
      established. We used the Xpert assay to test EBC, saliva, urine, and blood
      samples from HIV-negative, smear- and culture-positive pulmonary tuberculosis
      (TB) patients for the presence of M. tuberculosis. To compare the ability of the
      assay to perform bacterial load measurements on sputum samples with versus
      without sample processing, the assay was also performed on paired direct and
      processed sputum samples from each patient. The Xpert assay detected M.
      tuberculosis in none of the 26 EBC samples (sensitivity, 0.0%; 95% confidence
      interval [95% CI], 0.0%, 12.9%), 10 of the 26 saliva samples (sensitivity, 38.5%;
      95% CI, 22.4%, 57.5%), 1 of 26 urine samples (sensitivity, 3.8%; 95% CI, 0.7%,
      18.9%), and 2 of 24 blood samples (sensitivity, 8.3%; 95% CI, 2.3%, 25.8%). For
      bacterial load measurements in the different types of sputum samples, the cycle
      thresholds of the two M. tuberculosis-positive sputum types were well correlated
      (Spearman correlation of 0.834). This study demonstrates that the Xpert assay
      should not be routinely used to detect M. tuberculosis in EBC, saliva, urine, or
      blood samples from HIV-negative patients suspected of having pulmonary
      tuberculosis. As a test of bacterial load, the assay produced similar results
      when used to test direct versus processed sputum samples. Sputum remains the
      optimal sample type for diagnosing pulmonary tuberculosis in HIV-negative
      patients with the Xpert assay. 

PMID- 24108611
TI  - Comparison of multilocus variable-number tandem-repeat analysis and whole-genome
      sequencing for investigation of Clostridium difficile transmission.
AB  - No study to date has compared multilocus variable-number tandem-repeat analysis
      (MLVA) and whole-genome sequencing (WGS) in an investigation of the transmission
      of Clostridium difficile infection. Isolates from 61 adults with ongoing and/or
      recurrent C. difficile infections and 17 asymptomatic carriage episodes in
      children (201 samples), as well as from 61 suspected outbreaks affecting 2 to 41
      patients in 31 hospitals in the United Kingdom (300 samples), underwent 7-locus
      MLVA and WGS in parallel. When the first and last samples from the same
      individual taken for a median (interquartile range [IQR]) of 63 days (43 to 105
      days) apart were compared, the estimated rates of the evolution of single
      nucleotide variants (SNVs), summed tandem-repeat differences (STRDs), and locus
      variants (LVs) were 0.79 (95% confidence interval [CI], 0.00 to 1.75), 1.63 (95%
      CI, 0.00 to 3.59), and 1.21 (95% CI, 0.00 to 2.67)/called genome/year,
      respectively. Differences of >2 SNVs and >10 STRDs have been used to exclude
      direct case-to-case transmission. With the first serial sample per individual
      being used to assess discriminatory power, across all pairs of samples sharing a
      PCR ribotype, 192/283 (68%) differed by >10 STRDs and 217/283 (77%) by >2 SNVs.
      Among all pairs of cases from the same suspected outbreak, 1,190/1,488 (80%)
      pairs had concordant results using >2 SNVs and >10 STRDs to exclude transmission.
      For the discordant pairs, 229 (15%) had >=2 SNVs but <=10 STRDs, and 69 (5%) had
      <=2 SNVs but >=10 STRDs. Discordant pairs had higher numbers of LVs than
      concordant pairs, supporting the more diverse measure in each type of discordant
      pair. Conclusions on whether the potential outbreaks were confirmed were
      concordant in 58/61 (95%) investigations. Overall findings using MLVA and WGS
      were very similar despite the fact that they analyzed different parts of the
      bacterial genome. With improvements in WGS technology, it is likely that MLVA
      locus data will be available from WGS in the near future. 

PMID- 24108612
TI  - Aspergillus PCR-based investigation of fresh tissue and effusion samples in
      patients with suspected invasive Aspergillosis enhances diagnostic capabilities.
AB  - Although it is a severe complication in immunocompromised patients, diagnosing
      invasive fungal disease (IFD), especially invasive aspergillosis (IA), remains
      difficult. In certain clinical scenarios, examining tissue samples for
      identification of the infectious organism becomes important. As culture-based
      methods rarely yield results, the performance of an Aspergillus-specific nested
      PCR in fresh tissue or pleural effusion samples was evaluated. Fresh tissue (n =
      59) and effusion (n = 47) specimens from 79 immunocompromised patients were
      subjected to an Aspergillus-specific PCR assay. Twenty-six patients had proven (n
      = 20) or probable (n = 6) IFD, according to the European Organization for
      Research and Treatment of Cancer/Invasive Fungal Infections Cooperative Group and
      National Institute of Allergy and Infectious Diseases Mycoses Study Group
      (EORTC/MSG) criteria, while the remaining patients were classified as having
      either possible IFD (n = 30) or no IFD (n = 23). IA was identified as the
      underlying IFD in 21/26 proven/probable cases. PCR positivity was observed for
      18/21 proven/probable and 6 possible IA cases; cases classified as no IA did not
      show positive signals. Patients with proven IFD (n = 5) with cultures positive
      for non-Aspergillus molds also had negative Aspergillus PCR results. Aspergillus
      PCR performance analysis yielded sensitivity and specificity values of 86% (95%
      confidence interval [CI], 65% to 95%) and 100% (95% CI, 86% to 100%),
      respectively, thus leading to a diagnostic odds ratio of >200. In this analysis,
      good diagnostic performance of the PCR assay for detection of IA was observed for
      tissue samples, while effusion samples showed lower sensitivity rates. PCR
      testing represents a complementary tool; a positive PCR result strengthens the
      likelihood of IA, whereas IA seems unlikely in cases with negative results but
      findings could indicate non-Aspergillus IFD. Thus, PCR testing of these specimens
      enhances the diagnostic capabilities. 

PMID- 24108613
TI  - Comparison of careHPV and hybrid capture 2 assays for detection of high-risk
      human Papillomavirus DNA in cervical samples from HIV-1-infected African women.
AB  - The careHPV and HC2 assays were compared for high-risk human papillomavirus (HR
      HPV) DNA detection in cervical samples from 149 HIV-1-infected African women. The
      HR-HPV DNA detection rates were 37.6% and 34.9% for careHPV and HC2,
      respectively. Agreement between the two tests was 94.6% (95% confidence interval
      [CI], 89.7% to 97.7%) with a kappa value of 0.88 (95% CI, 0.81 to 0.96),
      indicating an excellent agreement. careHPV may be considered as suitable as HC2
      for cervical cancer screening among HIV-infected African women. 

PMID- 24108614
TI  - Epidemiology, species distribution, antifungal susceptibility, and outcome of
      candidemia across five sites in Italy and Spain.
AB  - Candidemia has become an important bloodstream infection that is frequently
      associated with high rates of mortality and morbidity, and its growing incidence
      is related to complex medical and surgical procedures. We conducted a multicenter
      study in five tertiary care teaching hospitals in Italy and Spain and evaluated
      the epidemiology, species distribution, antifungal susceptibilities, and outcomes
      of candidemia episodes. In the period of 2008 to 2010, 995 episodes of candidemia
      were identified in these hospitals. The overall incidence of candidemia was 1.55
      cases per 1,000 admissions and remained stable during the 3-year analysis.
      Candida albicans was the leading agent of infection (58.4%), followed by Candida
      parapsilosis complex (19.5%), Candida tropicalis (9.3%), and Candida glabrata
      (8.3%). The majority of the candidemia episodes were found in the internal
      medicine department (49.6%), followed by the surgical ward, the intensive care
      unit (ICU), and the hemato-oncology ward. Out of 955 patients who were eligible
      for evaluation, 381 (39.9%) died within 30 days from the onset of candidemia.
      Important differences in the 30-day mortality rates were noted between
      institutions: the lowest mortality rate was in the Barcelona hospital, and the
      highest rate was in the Udine hospital (33.6% versus 51%, respectively; P =
      0.0005). Overall, 5.1% of the 955 isolates tested were resistant or susceptible
      dose dependent (SDD) to fluconazole, with minor differences between the hospitals
      in Italy and Spain (5.7% versus 3.5%, respectively; P = 0.2). Higher MICs for
      caspofungin were found, especially with C. parapsilosis complex (MIC90, 1
      MUg/ml). Amphotericin B had the lowest MICs. This report shows that candidemia is
      a significant source of morbidity in Europe, causing a substantial burden of
      disease and mortality. 

PMID- 24108615
TI  - Blue-carba, an easy biochemical test for detection of diverse carbapenemase
      producers directly from bacterial cultures.

PMID- 24108616
TI  - Duplex real-time PCR for rapid simultaneous detection of Batrachochytrium
      dendrobatidis and Batrachochytrium salamandrivorans in Amphibian samples.
AB  - Chytridiomycosis is a lethal fungal disease contributing to declines and
      extinctions of amphibian species worldwide. The currently used molecular
      screening tests for chytridiomycosis fail to detect the recently described
      species Batrachochytrium salamandrivorans. In this study, we present a duplex
      real-time PCR that allows the simultaneous detection of B. salamandrivorans and
      Batrachochytrium dendrobatidis. With B. dendrobatidis- and B. salamandrivorans
      specific primers and probes, detection of the two pathogens in amphibian samples
      is possible, with a detection limit of 0.1 genomic equivalent of zoospores of
      both pathogens per PCR. The developed real-time PCR shows high degrees of
      specificity and sensitivity, high linear correlations (r(2) > 0.995), and high
      amplification efficiencies (>94%) for B. dendrobatidis and B. salamandrivorans.
      In conclusion, the described duplex real-time PCR can be used to detect DNA of B.
      dendrobatidis and B. salamandrivorans with highly reproducible and reliable
      results. 

PMID- 24108617
TI  - Broad-range PCR-electrospray ionization mass spectrometry for detection and
      typing of adenovirus and other opportunistic viruses in stem cell transplant
      patients.
AB  - Hematopoietic stem cell transplant patients are highly susceptible to viral
      infections. Follow-up after transplantation includes weekly screening using
      single, virus-specific real-time PCR tests, mainly for viruses in the families
      Herpesviridae and Adenoviridae that contribute to a high morbidity, especially in
      pediatric populations. The Abbott PLEX-ID platform combines broad-range PCR with
      electrospray ionization mass spectrometry to enable the simultaneous detection of
      multiple pathogens in a single assay. The Viral IC Spectrum assay detects human
      adenoviruses, viruses from the family Herpesviridae (herpes simplex virus 1 [HSV
      1], HSV-2, cytomegalovirus [CMV], Epstein-Barr virus [EBV], varicella-zoster
      virus [VZV], and human herpesvirus 8 [HHV-8]), human enterovirus, polyomaviruses
      (BK and JC), and parvovirus B19. We evaluated the performance of the Viral IC
      Spectrum assay with samples from 16 adult and 36 pediatric stem cell transplant
      patients. The sensitivity of the Viral IC Spectrum assay compared to real-time
      PCR quantification using the adenovirus Rgene kit for the detection of adenovirus
      was 96.7% from plasma samples (n = 92) and 78% from stool samples (n = 100). No
      adenovirus was detected in samples from noninfected patients (n = 30). PLEX-ID
      species identification was perfectly concordant with species-specific real-time
      PCR assays. In plasma and stool samples, the level of amplified products measured
      by PLEX-ID and the quantity in copies/ml (r = 0.82 and 0.78, respectively) were
      correlated up to 6 log10 copies/ml. In 67.4% of adenovirus-positive plasma
      samples, at least one other viral infection was detected; these included BK virus
      (n = 41), CMV (n = 30), EBV (n = 26), JC virus (n = 9), and HSV-1 (n = 6). The
      results of this study suggest that the Viral IC Spectrum assay performed on the
      PLEX-ID platform is reliable for adenovirus infection diagnosis in
      immunocompromised patients. 

PMID- 24108618
TI  - The development of the Multidimensional Social Competence Scale: a standardized
      measure of social competence in autism spectrum disorders.
AB  - Autism and its related disorders are commonly described as lying along a
      continuum that ranges in severity and are collectively referred to as autism
      spectrum disorders (ASDs). Although all individuals with ASD meet the social
      impairment diagnostic criteria outlined in the DSM-IV-TR, they do not present
      with the same social difficulties. The variability in the expression and severity
      of social competence is particularly evident among the group of individuals with
      "high-functioning" ASD who appear to have difficulty applying their average to
      above average intelligence in a social context. There is a striking paucity of
      empirical research investigating individual differences in social functioning
      among individuals with high-functioning ASD. It is possible that more detailed
      investigations of social competence have been impeded by the lack of standardized
      measures available to assess the nature and severity of social impairment. The
      aim of the current study was to develop and evaluate a parent rating scale
      capable of assessing individual differences in social competence (i.e. strengths
      and challenges) among adolescents with ASD: the Multidimensional Social
      Competence Scale (MSCS). Results from confirmatory factor analyses supported the
      hypothesized multidimensional factor structure of the MSCS. Seven relatively
      distinct domains of social competence were identified including social
      motivation, social inferencing, demonstrating empathic concern, social knowledge,
      verbal conversation skills, nonverbal sending skills, and emotion regulation.
      Psychometric evidence provided preliminary support for the reliability and
      validity of the scale. Possible applications of this promising new parent rating
      scale in both research and clinical settings are discussed.

PMID- 24108620
TI  - How to Collect National Institute of Standards and Technology (NIST) Traceable
      Fluorescence Excitation and Emission Spectra.
AB  - Contemporary spectrofluorimeters comprise exciting light sources, excitation and
      emission monochromators, and detectors that without correction yield data not
      conforming to an ideal spectral response. The correction of the spectral
      properties of the exciting and emission light paths first requires calibration of
      the wavelength and spectral accuracy. The exciting beam path can be corrected up
      to the sample position using a spectrally corrected reference detection system.
      The corrected reference response accounts for both the spectral intensity and
      drift of the exciting light source relative to emission and/or transmission
      detector responses. The emission detection path must also be corrected for the
      combined spectral bias of the sample compartment optics, emission monochromator,
      and detector. There are several crucial issues associated with both excitation
      and emission correction including the requirement to account for spectral band
      pass and resolution, optical band-pass or neutral density filters, and the
      position and direction of polarizing elements in the light paths. In addition,
      secondary correction factors are described including (1) subtraction of the
      solvent's fluorescence background, (2) removal of Rayleigh and Raman scattering
      lines, as well as (3) correcting for sample concentration-dependent inner-filter
      effects. The importance of the National Institute of Standards and Technology
      (NIST) traceable calibration and correction protocols is explained in light of
      valid intra- and interlaboratory studies and effective spectral qualitative and
      quantitative analyses including multivariate spectral modeling. 

PMID- 24108619
TI  - Exome sequencing as a diagnostic tool for pediatric-onset ataxia.
AB  - Ataxia demonstrates substantial phenotypic and genetic heterogeneity. We set out
      to determine the diagnostic yield of exome sequencing in pediatric patients with
      ataxia without a molecular diagnosis after standard-of-care assessment in Canada.
      FORGE (Finding Of Rare disease GEnes) Canada is a nation-wide project focused on
      identifying novel disease genes for rare pediatric diseases using whole-exome
      sequencing. We retrospectively selected all FORGE Canada projects that included
      cerebellar ataxia as a feature. We identified 28 such families and a molecular
      diagnosis was made in 13; a success rate of 46%. In 11 families, we identified
      mutations in genes associated with known neurological syndromes and in two we
      identified novel disease genes. Exome analysis of sib pairs and/or patients born
      to consanguineous parents was more likely to be successful (9/13) than simplex
      cases (4/15). Our data suggest that exome sequencing is an effective first line
      test for pediatric patients with ataxia where a specific single gene is not
      immediately suspected to be causative.

PMID- 24108621
TI  - Steady-state fluorescence polarization/anisotropy for the study of protein
      interactions.
AB  - Fluorescence methods are often employed for the characterization of molecular
      interactions. In particular, polarization/anisotropy studies are widely utilized
      in the life sciences as they allow quantification of protein interactions in the
      micro- and nanomolar concentration range. Herein we shall briefly describe the
      theoretical aspects of polarization/anisotropy and outline an experiment for
      determination of the dissociation constant for a protein-ligand complex. 

PMID- 24108622
TI  - Quantitative fluorescence spectral analysis of protein denaturation.
AB  - This chapter describes a procedure of global analysis of the steady-state spectra
      measured with different concentrations of the denaturant to quantitatively study
      protein denaturation. With the help of physicochemical models, relevant spectral
      parameters that characterize the folding intermediate and thermodynamic
      parameters that describe a three-state model N-I-U can be estimated.

PMID- 24108623
TI  - High-pressure fluorescence applications.
AB  - Fluorescence is the most widely used technique to study the effect of pressure on
      biochemical systems. The use of pressure as a physical variable sheds light into
      volumetric characteristics of reactions. Here we focus on the effect of pressure
      on protein solutions using a simple unfolding example in order to illustrate the
      applications of the methodology. Topics covered in this review include the
      relationships between practical aspects and technical limitations; the effect of
      pressure and the study of protein cavities; the interpretation of thermodynamic
      and relaxation kinetics; and the study of relaxation amplitudes. Finally, we
      discuss the insights available from the combination of fluorescence and other
      methods adapted to high pressure, such as SAXS or NMR. Because of the simplicity
      and accessibility of high-pressure fluorescence, the technique is a starting
      point that complements appropriately multi-methodological approaches related to
      understanding protein function, disfunction, and folding from the volumetric
      point of view. 

PMID- 24108624
TI  - Frequency domain fluorometry: theory and application.
AB  - Frequency domain fluorometry is a widely utilized tool in the physical, chemical,
      and biological sciences. This chapter focuses on the theory of the method and the
      practical aspects required to carry out intensity decay, i.e., lifetime
      measurements on a modern frequency domain fluorometer. Several
      chemical/biological systems are utilized to illustrate data acquisition
      protocols. Data analysis procedures and methodologies are also discussed. 

PMID- 24108625
TI  - Polar plot representation of time-resolved fluorescence.
AB  - Measuring changes in a molecule's fluorescence emission is a common technique to
      study complex biological systems such as cells and tissues. Although the steady
      state fluorescence intensity is frequently used, measuring the average amount of
      time that a molecule spends in the excited state (the fluorescence lifetime)
      reveals more detailed information about its local environment. The lifetime is
      measured in the time domain by detecting directly the decay of fluorescence
      following excitation by short pulse of light. The lifetime can also be measured
      in the frequency domain by recording the phase and amplitude of oscillation in
      the emitted fluorescence of the sample in response to repetitively modulated
      excitation light. In either the time or frequency domain, the analysis of data to
      extract lifetimes can be computationally intensive. For example, a variety of
      iterative fitting algorithms already exist to determine lifetimes from samples
      that contain multiple fluorescing species. However, recently a method of analysis
      referred to as the polar plot (or phasor plot) is a graphical tool that projects
      the time-dependent features of the sample's fluorescence in either the time or
      frequency domain into the Cartesian plane to characterize the sample's lifetime.
      The coordinate transformations of the polar plot require only the raw data, and
      hence, there are no uncertainties from extensive corrections or time-consuming
      fitting in this analysis. In this chapter, the history and mathematical
      background of the polar plot will be presented along with examples that highlight
      how it can be used in both cuvette-based and imaging applications. 

PMID- 24108626
TI  - Ensemble and single-molecule detected time-resolved FRET methods in studies of
      protein conformations and dynamics.
AB  - Most proteins are nanomachines that are selected to execute specific functions
      and therefore should have some degree of flexibility. The driving force that
      excites specific motions of domains and smaller chain elements is the thermal
      fluctuations of the solvent bath which are channeled to selected modes of motions
      by the structural constraints. Consequently characterization of the ensembles of
      conformers of proteins and their dynamics should be expressed in statistical
      terms, i.e., determination of probability distributions of the various
      conformers. This can be achieved by measurements of time-resolved dynamic non
      radiative excitation energy transfer (trFRET) within ensembles of site
      specifically labeled protein molecules. Distributions of intramolecular segmental
      end-to-end distances and their fast fluctuations can be determined, and fast and
      slow conformational transitions within selected sections of the molecule can be
      monitored and analyzed. Both ensemble and single-molecule detection methods can
      be applied for data collection. In combination with synchronization methods, time
      resolved FRET was also used for studies of fast conformational transitions, in
      particular the folding/unfolding transitions. 

PMID- 24108627
TI  - MD + QM correlations with tryptophan fluorescence spectral shifts and lifetimes.
AB  - Principles behind quenching of tryptophan (Trp) fluorescence are updated and
      extended in light of recent 100-ns and 1-MUs molecular dynamics (MD) trajectories
      augmented with quantum mechanical (QM) calculations that consider electrostatic
      contributions to wavelength shifts and quenching. Four studies are summarized,
      including (1) new insight into the single exponential decay of NATA, (2) a study
      revealing how unsuspected rotamer transitions affect quenching of Trp when used
      as a probe of protein folding, (3) advances in understanding the origin of
      nonexponential decay from 100-ns simulations on 19 Trps in 16 proteins, and (4)
      the correlation of wavelength with lifetime for decay-associated spectra (DAS).
      Each study strongly reinforces the concept that-for Trp-electron transfer-based
      quenching is controlled much more by environment electrostatic factors affecting
      the charge transfer (CT) state energy than by distance dependence of electronic
      coupling. In each case, water plays a large role in unexpected ways. 

PMID- 24108628
TI  - Analysis of time-dependent red shifts in fluorescence emission from tryptophan
      residues in proteins.
AB  - Instantaneous fluorescence emission spectra measured at different times after
      excitation often shift to the red as the delay between the excitation pulse and
      fluorescence detection is increased. In the case of Trp fluorescence in proteins,
      the time-dependent red shift (TDRS) may have its origins in relaxation,
      heterogeneity, or a mixture of the two. In those cases where it is possible to
      rule out the contribution of heterogeneity, the TDRS can be used to study
      nonequilibrium relaxation dynamics of the protein matrix and the solvent on the
      picosecond and nanosecond time scales. Here we describe the experimental and
      computational procedures involved in recording spectrally and time-resolved
      fluorescence, detecting heterogeneity, and extracting information about
      protein/solvent relaxation dynamics. 

PMID- 24108629
TI  - Global analysis of time-resolved fluorescence data.
AB  - In this chapter, we describe the global analysis approach for processing time
      resolved fluorescence spectroscopy data of molecules in the condensed phase.
      Combining simultaneous analysis of data measured under different experimental
      conditions (spatial coordinates, temperature, concentration, emission wavelength,
      excitation intensity, etc.) with the fitting strategy, enabling parameter linkage
      and thus decreasing the total amount of estimated variables, makes global
      analysis more robust and more consistent compared to a sequential fit of single
      experimental data. We consider the main stages of the global analysis approach
      and provide some details that are important for its practical implementation. The
      application of the global approach to the analysis of time-resolved fluorescence
      anisotropy is demonstrated on experimental data of (enhanced) green fluorescent
      protein in aqueous solution. 

PMID- 24108630
TI  - Nanometrology.
AB  - Methods and protocols are described when using fluorescence metrology to
      determine the average nanoparticle (np) size in colloids in the range of 1-10 nm.
      The technique is based on determining the rotational correlation time of the np
      from the decay of fluorescence anisotropy of a dye that is electrostatically or
      covalently attached to the np as it undergoes Brownian rotation. The np size is
      then calculated from the Stokes-Einstein equation. The exemplar of silica nps is
      presented, but the approach can also be applied to other types of nps.

PMID- 24108632
TI  - Subpicosecond Kerr-gate spectrofluorometry.
AB  - This chapter describes an experimental layout for time and spectrally resolved
      fluorescence measurements with femtosecond time resolution based on Kerr gating.
      The combination of data recorded using different Kerr media allows a temporal
      dynamic range from ~100 fs to several nanoseconds. Simultaneous analysis of
      multiple datasets is described.

PMID- 24108631
TI  - Upconversion spectrophotofluorometry.
AB  - As the other chapters attest, sensitivity of fluorescent molecules to their local
      environment has created powerful tools in the study of molecular biology,
      particularly in the study of protein, DNA, and lipid dynamics. Surprisingly, even
      events faster than the nanosecond lifetimes of fluorophores are important in
      protein function, and in particular, events lasting just a few ps reflect on
      water motion and the coupled dynamics of proteins. These ultrafast phenomena can
      best be studied by using the same laser that excites fluorescence to also
      "strobe" the emission, providing sub-picosecond time slices of the action. We
      explain the strobing "upconversion" technique and some limits on its execution. 

PMID- 24108633
TI  - Photoinduced electron transfer modeling to simulate flavoprotein fluorescence
      decay.
AB  - A method of analysis is described on the photoinduced electron transfer (PET)
      from aromatic amino acids as tryptophans (Trp) and tyrosines (Tyr) to the excited
      isoalloxazine (Iso*) in FMN-binding proteins (FBP) from Desulfovibrio vulgaris
      (strain, Miyazaki F). Time-dependent geometrical factors as the donor-acceptor
      distances are determined by means of a molecular dynamics simulation (MDS) of the
      proteins. Fluorescence decays of the single mutated isoforms of FBP are used as
      experimental data. The electrostatic (ES) energy between the photoproducts and
      ionic groups in the proteins is introduced into the Kakitani and Mataga (KM)
      model, which is modeled for an electron transfer process in solution. The PET
      parameters contained in the KM rate are determined by means of a nonlinear least
      square method, according to the Marquardt algorithm. The agreement between the
      observed and calculated decays is quite good, but not optimal. Characteristics on
      PET in flavoproteins, obtained by the present method, are described. Possible
      improvements of the method are discussed. 

PMID- 24108634
TI  - Biosynthetic incorporation of tryptophan analogs in proteins.
AB  - Biosynthetic incorporation of Trp analogs in a protein can help in its
      characterization using fluorescence spectroscopy and other methodologies like NMR
      and phosphorescence. Here a protocol is presented resulting in the efficient
      incorporation of Trp analogs in a recombinant protein, using an Escherichia coli
      Trp auxotroph. An overview of recent developments in the Trp analog incorporation
      field is also presented. 

PMID- 24108635
TI  - Optimization of fluorescent proteins.
AB  - Nowadays, fluorescent protein (FP) variants have been engineered to fluoresce in
      all different colors; to display photoswitchable, or photochromic, behavior; or
      to show yet other beneficial properties that enable or enhance a still growing
      set of new fluorescence spectroscopy and microcopy techniques. This has allowed
      the (in situ) study of biomolecules with unprecedented resolution, specificity,
      sensitivity, and ease of labeling. However, brighter FPs, more photostable FPs,
      and FPs that display an even better compatibility with biophysical
      microspectroscopic techniques are still highly desired. The key characteristics
      of FPs-absorption spectrum, emission spectrum, brightness, fluorescence lifetime,
      maturation rate, oligomeric state, photostability, pH sensitivity, and
      functionality in protein fusions-determine their application. This chapter will
      describe these key features and present several experimental protocols to
      optimize them.The optimization procedure contains three steps. First the amino
      acid sequence of a template FP is changed via random or site-directed
      mutagenesis. A primary screening based on fluorescence intensity, fluorescence
      lifetime, and emission spectrum is applied on the FP libraries expressed in
      bacteria. The most promising mutants are isolated, purified, and characterized in
      vitro. In this step all key characteristics are determined experimentally.
      Finally the new FPs are evaluated for use in vivo. The protein production and
      maturation is monitored in bacteria, while transfected mammalian cells report on
      the photostability, relative brightness, and correct localization to various
      subcellular compartments. 

PMID- 24108636
TI  - Monitoring membrane properties and apoptosis using membrane probes of the 3
      hydroxyflavone family.
AB  - Environment-sensitive fluorescent membrane probes are attractive tools for
      investigating the membrane properties and their changes under perturbing
      conditions. Membrane probes of the 3-hydroxyflavone family are of particular
      interest due to their excited-state intramolecular proton transfer (ESIPT)
      reaction, which confers a dual emission highly sensitive to the polarity and
      hydration of the environment. In the present work, we will describe the protocols
      used with these probes in order to monitor the physicochemical properties of
      lipid membrane models and cell plasma membranes and to detect apoptosis. 

PMID- 24108637
TI  - Rectangle FRAP for measuring diffusion with a laser scanning microscope.
AB  - Fluorescence recovery after photobleaching (FRAP) is one of the most useful
      microscopy techniques for studying the mobility of molecules in terms of a
      diffusion coefficient. Here, we describe a FRAP method that allows such
      measurements, relying on the photobleaching of a rectangular region of any size
      and aspect ratio. We start with a brief overview of the rectangle FRAP theory,
      and next we provide guidelines for performing FRAP measurements, including a
      discussion of the experimental setup and the data analysis. Finally, we discuss
      how to verify correct use of the rectangle FRAP method using test solutions. 

PMID- 24108638
TI  - A quantitative protocol for intensity-based live cell FRET imaging.
AB  - Forster resonance energy transfer (FRET) has become one of the most ubiquitous
      and powerful methods to quantify protein interactions in molecular biology. FRET
      refers to the sensitization of an acceptor molecule through transfer of energy
      from a nearby donor, and it can occur if the emission band of the donor exhibits
      spectral overlap with the absorption band of the acceptor molecule. Numerous
      methods exist to quantify FRET levels from interacting protein labels including
      fluorescence lifetime, acceptor photobleaching, and polarization-resolved imaging
      (Lakowicz, Principles of fluorescence spectroscopy, 2006; Jares-Erijman and
      Jovin, Curr Opin Chem Biol 10(5):409-416, 2006; van Munster and Gadella,
      Microscopy techniques, 2005). For live cell imaging, however, sensitized emission
      FRET (seFRET) is the most powerful and robust method of FRET signal
      quantification (Chakrabortee et al., Proc Natl Acad Sci USA 107(37):16084-16089,
      2010). It is fast, can be applied using straight forward microscopy equipment,
      and offers information not only on strength of interaction but, uniquely, also on
      the relative changes between interacting and noninteracting moieties in the
      reaction, referred to as FRET stoichiometry. A rigorous and quantitative
      application of seFRET is far from trivial, however, and requires appropriate
      calibration experiments and constructs, control over hardware settings, and
      appropriate image processing steps.This protocol presents a rigorous method to
      perform quantitative seFRET measurements in live cells, providing the maximum
      possible information content from the measurement. The theoretical development
      and validation of the method is described in detail in Elder et al. (J R Soc
      Interface 6:S59-S81, 2009) where it is also demonstrated in the kinetic ("time
      lapse") analysis of protein interactions governing mitosis. The present protocol
      gives a detailed recipe for application of seFRET. It is written specifically for
      use with CFP (cyan fluorescence protein) as donor fluorophore and YFP (yellow
      fluorescent protein) as acceptor fluorophore, a popular choice for many
      experiments. The protocol is however valid for any other FRET fluorophore pair,
      and we indicate how to adapt the protocol in such situations. We also provide a
      software program that automates the calibration tasks outlined in this protocol
      and which is available for free to download (
      http://wiki.laser.ceb.cam.ac.uk/wiki/index.php/Resources ). 

PMID- 24108639
TI  - Wide-field fluorescence lifetime imaging with multi-anode detectors.
AB  - Fluorescence lifetime imaging microscopy (FLIM) has become a powerful and widely
      used tool to monitor inter- and intramolecular dynamics of fluorophore-labeled
      proteins inside living cells.Here, we present recent achievements in the
      construction of a positional sensitive wide-field single-photon counting detector
      system to measure fluorescence lifetimes in the time domain and demonstrate its
      usage in FRET applications.The setup is based on a conventional fluorescence
      microscope equipped with synchronized short-pulse lasers that illuminate the
      entire field of view at minimal invasive intensities, thereby enabling long-term
      experiments of living cells. The system is capable to acquire single-photon
      counting images and measures directly the transfer rate of fast photophysical
      processes as, for instance, FRET, in which it can resolve complex fluorescence
      decay kinetics. 

PMID- 24108640
TI  - Global analysis of FRET-FLIM data in live plant cells.
AB  - This chapter describes the procedure for globally analyzing fluorescence lifetime
      imaging (FLIM) data for the observation and quantification of Forster resonance
      energy transfer (FRET) in live plant cells. The procedure is illustrated by means
      of a case study, for which plant protoplasts were transfected with different
      visible fluorescent proteins and subsequently imaged using two-photon excitation
      FLIM. Spatially resolved fluorescence lifetime images were obtained by
      application of global analysis using the program Glotaran, which is open-source
      and freely available software. Using this procedure it is possible to extract the
      fraction and distance of interacting species between, or conformational changes
      within proteins, from complex experimental FRET-FLIM datasets, even at low signal
      to-noise ratios. In addition, the software allows excluding inherently present
      autofluorescence from the plant cells, which improves the accuracy of the FRET
      analysis. The results from the case study are presented and interpreted in the
      context of the current scientific understanding of these biological systems. 

PMID- 24108642
TI  - Multimodal fluorescence imaging spectroscopy.
AB  - Multimodal fluorescence imaging is a versatile method that has a wide application
      range from biological studies to materials science. Typical observables in
      multimodal fluorescence imaging are intensity, lifetime, excitation, and emission
      spectra which are recorded at chosen locations at the sample. This chapter
      describes how to build instrumentation that allows for multimodal fluorescence
      imaging and explains data analysis procedures for the observables. 

PMID- 24108641
TI  - Time-resolved fluorescence anisotropy imaging.
AB  - Fluorescence can be characterized by its intensity, position, wavelength,
      lifetime, and polarization. The more of these features are acquired in a single
      measurement, the more can be learned about the sample, i.e., the microenvironment
      of the fluorescence probe. Polarization-resolved fluorescence lifetime imaging
      time-resolved fluorescence anisotropy imaging, TR-FAIM-allows mapping of
      viscosity or binding or of homo-FRET which can indicate dimerization or generally
      oligomerization. 

PMID- 24108643
TI  - Application of fluorescence correlation spectroscopy (FCS) to measure the
      dynamics of fluorescent proteins in living cells.
AB  - Fluorescence correlation spectroscopy (FCS) can add dynamic molecular information
      to images of live cells. For example, a confocal laser scanning microscope (CLSM)
      equipped with an accessory FCS unit provides the possibility to first image the
      spatial distribution of a fluorescent protein before probing its mobility within
      defined regions of interest. Whereas specific protein-protein interactions are
      preferably assayed with a dual-color approach, single-color FCS can still provide
      valuable information about the size of the diffusing entities and potential
      interactions with other, nonfluorescent, proteins or subcellular structures.
      Because number fluctuations are measured, the concentrations of freely diffusing
      complexes and their state of oligomerization are accessible. 

PMID- 24108644
TI  - Fluorescence cross-correlation spectroscopy (FCCS) in living cells.
AB  - Fluorescence cross-correlation spectroscopy (FCCS) is a single-molecule sensitive
      technique to quantitatively study interactions among fluorescently tagged
      biomolecules. Besides the initial implementation as dual-color FCCS (DC-FCCS),
      FCCS has several powerful derivatives, including single-wavelength FCCS (SW
      FCCS), two-photon FCCS (TP-FCCS), and pulsed interleaved excitation FCCS (PIE
      FCCS). However, to apply FCCS successfully, one needs to be familiar with
      procedures ranging from fluorescent labeling, instrumentation setup and
      alignment, sample preparation, and data analysis. Here, we describe the
      procedures to apply FCCS in various biological samples ranging from live cells to
      in vivo measurements, with the focus on DC-FCCS and SW-FCCS. 

PMID- 24108645
TI  - Quantifying lipid-protein interaction by fluorescence correlation spectroscopy
      (FCS).
AB  - Fluorescence correlation spectroscopy (FCS) is a powerful method to investigate
      molecular interactions based on the variation of diffusion properties at the
      single-molecule level. This technique allows studying quantitatively the
      interaction of fluorescently labeled proteins/peptides with lipid vesicles. Here,
      we describe how to acquire and analyze FCS partition data in order to accurately
      determine the protein/peptide partition coefficients between the aqueous and
      lipid phases. It is shown that the recovery of unbiased partition coefficients
      from FCS partition curves (fractional amplitude of the bound species versus lipid
      concentration) requires considering explicitly the Poissonian loading of the
      lipid vesicles with the fluorescently labeled protein in order to account for the
      variable liposome brightness in each sample. Additionally, the impact of a trace
      amount of a fluorescent non-binding component on the partition curves determined
      by FCS is also discussed. 

PMID- 24108646
TI  - PET-FCS: probing rapid structural fluctuations of proteins and nucleic acids by
      single-molecule fluorescence quenching.
AB  - Quenching of organic fluorophores by aromatic amino acids and DNA nucleotides
      with expelled electron donating properties allows the study of conformational
      dynamics of biomolecules. Efficient fluorescence quenching via photoinduced
      electron transfer (PET) requires van der Waals contact and can be used as
      reporter for structural fluctuations at the 1-nm scale in proteins, peptides, and
      nucleic acids. The combination of PET with fluorescence correlation spectroscopy
      (FCS) establishes a powerful method (PET-FCS) to study equilibrium dynamics at
      the single-molecule level on time scales from nano- to milliseconds. We delineate
      the fundamentals of PET-based fluorescence quenching, reporter engineering,
      instrumental and experimental design, and provide examples. 

PMID- 24108647
TI  - Z-scan fluorescence correlation spectroscopy as a tool for diffusion measurements
      in planar lipid membranes.
AB  - Studies of lateral diffusion are used for the characterization of the dynamics of
      biological membranes. One of the techniques that can be used for this purpose is
      fluorescence correlation spectroscopy (FCS), which belongs to the single-molecule
      techniques. Unfortunately, FCS measurements, when performed in planar lipid
      systems, are associated with a few sources of inaccuracy in the determination of
      the lateral diffusion coefficient. The main problems are related to the imperfect
      positioning of the laser focus relative to the plane of the sample. Another
      source of inaccuracy is the requirement for external calibration of the detection
      volume size. This protocol introduces a calibration-free method called Z-scan
      fluorescence correlation spectroscopy (Z-scan FCS), which is based on the
      determination of the diffusion time and particle number in steps along the
      optical (z-) axis by sequential FCS measurements. Z-scan FCS could be employed
      for diffusion measurements in planar membrane model systems-supported
      phospholipid bilayers (SPBs) and giant unilamellar vesicles (GUVs) and also in
      biological membranes. A result from measurements in SPBs is also presented in the
      protocol as a principle example of the Z-scan technique. 

PMID- 24108648
TI  - Scanning fluorescence correlation spectroscopy (SFCS) with a scan path
      perpendicular to the membrane plane.
AB  - Scanning fluorescence correlation spectroscopy (SFCS) with a scan path
      perpendicular to the membrane plane was introduced to measure diffusion and
      interactions of fluorescent components in free-standing biomembranes. Using a
      confocal laser scanning microscope (CLSM), the open detection volume is
      repeatedly scanned through the membrane at a kHz frequency. The fluorescence
      photons emitted from the detection volume are continuously recorded and stored in
      a file. While the accessory hardware requirements for a conventional CLSM are
      minimal, data evaluation can pose a bottleneck. The photon events must be
      assigned to each scan, in which the maximum signal intensities have to be
      detected, binned, and aligned between the scans, in order to derive the membrane
      related intensity fluctuations of one spot. Finally, this time-dependent signal
      must be correlated and evaluated by well-known FCS model functions. Here we
      provide two platform-independent, open source software tools (PyScanFCS and
      PyCorrFit) that allow to perform all of these steps and to establish
      perpendicular SFCS in its one- or two-focus as well as its single- or dual-color
      modality. 

PMID- 24108649
TI  - Implementation and application of pulsed interleaved excitation for dual-color
      FCS and RICS.
AB  - Pulsed interleaved excitation (PIE) employs pulsed laser sources that are
      interleaved such that differentially colored fluorophores can be measured or
      imaged quasi-simultaneously in the absence of spectral crosstalk. PIE improves
      the robustness and reduces data analysis complexity of many fluorescence
      techniques, such as fluorescence cross-correlation spectroscopy (FCCS) and raster
      image cross-correlation spectroscopy (ccRICS), two methods used for quantitative
      investigation of molecular interactions in vitro and in living cells. However, as
      PIE is most often used for fluorescence fluctuation spectroscopy and burst
      analysis experiments and utilizes time-correlated single-photon counting
      detection and advanced optoelectronics, it has remained a technique that is
      mostly used by specialized single-molecule research groups. This protocols
      chapter provides an accessible overview of PIE for anyone considering
      implementing the method on a homebuilt or commercial microscope. We give details
      on the instrumentation, data collection and analysis software, on how to properly
      set up and align a PIE microscope, and finally, on how to perform proper dual
      color FCS and RICS experiments. 

PMID- 24108650
TI  - Quantitative study of protein-protein interactions in live cell by dual-color
      fluorescence correlation spectroscopy.
AB  - Dual-color FCS is a powerful method to monitor protein-protein interactions in
      living cells. The main idea is based on the cross-correlation analysis of
      temporal fluorescence intensity fluctuations of two fluorescent proteins to
      obtain their co-diffusion and relative concentration. But, when performing these
      experiments, the spectral overlap in the emission of the two colors produces an
      artifact that corrupts the cross-correlation data: spectral bleed-through. We
      have shown that problems with cross talk are overcome with Fluorescence Lifetime
      Correlation Spectroscopy (FLCS). FLCS applied to dual-color cross-correlation,
      utilizing for example eGFP and mCherry fluorescent proteins, allows the
      determination of protein-protein interactions in living cells without the need of
      spectral bleed-through calibration. Here, we present in detail how this
      methodology can be implemented using a commercial setup (Microtime from
      PicoQuant, SP8 SMD from Leica or any conventional confocal with PicoQuant TCSPC
      module, and also with a Becker and Hickl TCSPC module). The dual-color FLCS
      experimental procedure where the different laser intensities do not have to be
      controlled during the experiment constitutes a very powerful technique to
      quantitatively study protein interactions in live samples. 

PMID- 24108651
TI  - Brightness experiments.
AB  - This chapter presents an overview of quantitative fluorescence brightness
      experiments with special emphasis on single-color measurements of protein homo
      interactions inside living cells. We discuss practical considerations in the
      choice of the fluorescent labels and the calibration measurements necessary for
      quantitative interpretation of brightness experiments. Methods to identify and
      avoid common pitfalls, such as bleaching and saturation, are addressed. We
      examine the interpretation of brightness data with moment analysis. In
      particular, we focus on how to avoid or correct for undersampling, as well as how
      to characterize and adjust for photon detector effects. We conclude by describing
      brightness titration experiments which determine the binding curve and
      stoichiometry of a protein from apparent brightness data. 

PMID- 24108652
TI  - Global analysis of autocorrelation functions and photon counting distributions in
      fluorescence fluctuation spectroscopy.
AB  - In fluorescence correlation spectroscopy (FCS) and photon counting histogram
      (PCH) analysis, the same experimental fluorescence intensity fluctuations are
      used, but each analytical method focuses on a different property of the signal.
      The time-dependent decay of the correlation of fluorescence fluctuations is
      measured in FCS yielding molecular diffusion coefficients and triplet-state
      parameters such as fraction and decay time. The amplitude distribution of these
      fluctuations is calculated by PCH analysis yielding the molecular brightness.
      Both FCS and PCH give information about the molecular concentration. Here we
      describe a global analysis protocol that simultaneously recovers relevant and
      common parameters in model functions of FCS and PCH from a single fluorescence
      fluctuation trace. Application of a global analysis approach allows increasing
      the information content available from a single measurement that results in more
      accurate values of molecular diffusion coefficients and triplet-state parameters
      and also in robust, time-independent estimates of molecular brightness and number
      of molecules. 

PMID- 24108653
TI  - Simulation of autocorrelation function and photon counting distribution in
      fluorescence fluctuation spectroscopy.
AB  - In modern fluorescence fluctuation spectroscopy, the autocorrelation function and
      photon counting distribution are two widely used statistical characteristics of
      the measured fluctuating fluorescence intensity signal. Applying special analysis
      methods such as fluorescence correlation spectroscopy (FCS) and photon counting
      histogram (PCH) to these properties, it is possible to recover values of
      different parameters of fluorescent molecules such as the concentration,
      diffusion coefficient, molecular brightness, and kinetic rate constants. The
      development of new analysis methods is senseless without testing their validity,
      accuracy, and robustness. The most appropriate check of a method is its
      application to experimental data. However, sometimes it is more convenient and
      easier to verify a method on simulated data. Simulation is also useful for better
      understanding the processes that were modeled during the development of analysis
      methods. Here, we present two simulation models providing an autocorrelation
      function and photon counting distribution of a sequence of photon arrival times
      detected in fluorescence fluctuation spectroscopy. 

PMID- 24108654
TI  - Single-molecule fluorescence of nucleic acids.
AB  - Single-molecule fluorescence studies of nucleic acids are revolutionizing our
      understanding of fundamental cellular processes related to DNA and RNA processing
      mechanisms. Detailed molecular insights into DNA repair, replication,
      transcription, and RNA folding and function are continuously being uncovered by
      using the full repertoire of single-molecule fluorescence techniques. The
      fundamental reason behind the stunning growth in the application of single
      molecule techniques to study nucleic acid structure and dynamics is the unmatched
      ability of single-molecule fluorescence, and mostly single-molecule FRET, to
      resolve heterogeneous static and dynamic populations and identify transient and
      low-populated states without the need for sample synchronization. New advances in
      DNA and RNA synthesis, post-synthetic dye-labeling methods, immobilization and
      passivation strategies, improved dye photophysics, and standardized analysis
      methods have enabled the implementation of single-molecule techniques beyond
      specialized laboratories. In this chapter, we introduce the practical aspects of
      applying single-molecule techniques to investigate nucleic acid structure,
      dynamics, and function. 

PMID- 24108655
TI  - Photoswitchable fluorescent proteins for superresolution fluorescence microscopy
      circumventing the diffraction limit of light.
AB  - In the last two decades, fluorescent proteins became an indispensable tool to
      noninvasively label a protein in living cells. The discovery of photoswitchable
      fluorescent proteins expanded the applications of the fluorescent proteins to
      techniques such as molecular tracking and highlighting on a microscope. Recently,
      a new microscopic modality to achieve a superresolution circumventing the
      diffraction limit of light (photoactivated localization microscopy, PALM) has
      been developed based on the photoswitchable fluorescent proteins. Here we
      introduce a basic protocol of PALM through the visualization of actin bundles
      with superresolution. 

PMID- 24108656
TI  - Temporal bone squamous cell carcinoma: analyzing prognosis with univariate and
      multivariate models.
AB  - OBJECTIVES/HYPOTHESIS: Temporal bone squamous cell carcinoma (SCC) is an uncommon
      malignancy accounting for less than 0.2% of head and neck cancers. Despite
      advances in its early diagnosis, skull base microsurgery, radiotherapy, and
      integrated treatments, prognosis in advanced SCCs remains dismal. The present
      study aimed to analyze the clinicopathological variables potentially influencing
      outcome in a series of temporal bone SCCs. STUDY DESIGN: The prognosis of 41
      patients with temporal bone SCC was assessed retrospectively using univariate and
      multivariate statistical approaches. PATIENTS AND METHODS: Twenty-two women and
      19 men consecutively operated for primary temporal bone SCC with a curative
      intent at a tertiary referral center between 1980 and 2008. RESULTS: On
      univariate analysis, cT stage correlated with disease-free survival in months
      (DFS) (P = 0.037), and pT stage correlated with recurrence rate (P = 0.038), DFS
      (P = 0.013), and disease-specific survival (DSS) (P = 0.025). Lymph node status
      (cN0 or pN0 vs. pN+) was associated with DFS (P = 0.025). SCC grading correlated
      significantly with recurrence rate (P = 0.005), DFS (P = 0.004), and DSS (P =
      0.0036). Dura mater involvement was significantly associated with a higher
      recurrence rate (P = 0.001), a shorter DFS (P = 0.00001), and a lower DSS (P =
      0.0001). On multivariate analysis, only dura mater involvement (P = 0.001) and N
      status (P = 0.012) remained independently prognostic of DFS. CONCLUSION:
      Recurrences occurred despite obtaining block resections according to the tumor's
      clinical stage and pathologically free margins in all cases. Further analyses are
      mandatory to investigate hidden microscopic pathways of tumor diffusion,
      particularly in bone. Multi-institutional protocols are needed to facilitate
      comparisons between studies and enable meaningful meta-analyses.

PMID- 24108657
TI  - Structure-property relationships and (1)O)2) photosensitisation in sterically
      encumbered diimine Pt(II) acetylide complexes.
AB  - A series of sterically encumbered [Pt(L)(sigma-acetylide)2 ] complexes were
      prepared in which L, a dendritic polyaromatic diimine ligand, was held constant
      (L=1-(2,2'-bipyrid-6-yl)-2,3,4,5-tetrakis(4-tert-butylphenyl)benzene) and the cis
      ethynyl co-ligands were varied. The optical properties of the complexes were
      tuned by changing the electronic character, extent of pi conjugation and steric
      bulk of the ethynyl ligands. Replacing electron-withdrawing phenyl-CF3
      substituents (4) with electron-donating pyrenes (5) resulted in a red shift of
      both the lowest-energy absorption (DeltaE=3300 cm(-1) , 61 nm) and emission bands
      (DeltaE=1930 cm(-1) , 64 nm). The emission, assigned in each case as
      phosphorescence on the basis of the excited-state lifetimes, switched from being
      (3) MMLL'CT-derived (mixed metal-ligand-to-ligand charge transfer) when
      phenyl/polyphenylene substituents (3, 4, 6) were present, to ligand-centred (3)
      pipi* when the substituents were more conjugated aromatic platforms [pyrene (5)
      or hexa-peri-hexabenzocoronene (7)]. The novel Pt(II) acetylide complexes 5 and 7
      absorb strongly in the visible region of the electromagnetic spectrum, which
      along with their long triplet excited-state lifetimes suggested they would be
      good candidates for use as singlet-oxygen photosensitisers. Determined by in situ
      photooxidation of 1,5-dihydroxynaphthalene (DHN), the photooxidation rate with
      pyrenyl-5 as sensitiser (kobs =39.3*10(-3)  min(-1) ) was over half that of the
      known (1) O2 sensitiser tetraphenylporphyrin (kobs =78.6*10(-3)  min(-1) ) under
      the same conditions. Measured (1) O2 quantum yields of complexes 5 and 7 were
      half and one-third, respectively, of that of TPP, and thus reveal an efficient
      triplet-triplet energy-transfer process in both cases. 

PMID- 24108658
TI  - The hutterite variant of Treacher Collins syndrome: a 28-year-old story solved.
AB  - Treacher Collins syndrome (TCS), the best known form of mandibulofacial
      dysostosis (MFD) comprises a recognizable pattern of anomalies. In 1985, Lowry et
      al. reported on two Hutterite sisters born to apparently unaffected parents with
      TCS, raising the possibility of an autosomal recessive (AR) variant of TCS,
      subsequently given a unique Mendelian Inheritance of Man (MIM) number (248390).
      Recently, biallelic mutations in POLR1C were found in TCS patients, confirming AR
      TCS as a distinct entity. The Hutterites, an endogamous Anabaptist group, like
      other genetically isolated populations, provide a powerful resource for mapping
      AR disorders. We elected to study the molecular basis of TCS in the Hutterite
      population including the original kindred described in 1985, and another
      unrelated Hutterite patient. Prior to starting this study, a TCOF1 mutation had
      apparently been excluded in the original family at two outside institutions. We
      hypothesized that an AR variant of TCS was present in the three Hutterite
      patients, but homozygosity mapping did not show convincing evidence of shared
      regions between the affected individuals. TCOF1 analysis was undertaken and
      mutations were found in the three affected patients and an unaffected parent.
      These data show that the initial Hutterite family reported with AR TCS in fact
      has classic TCS due to a TCOF1 mutation, despite recent data confirming the
      existence of AR TCS in other populations. These results have significant
      counseling implications for the affected families in the Hutterite population and
      in the population at large. (c) 2013 Wiley Periodicals, Inc. 

PMID- 24108659
TI  - Dynamic display of bioactivity through host-guest chemistry.

PMID- 24108660
TI  - Pharmacological modulation of procoagulant microparticles improves haemodynamic
      dysfunction during septic shock in rats.
AB  - Circulating microparticles play a pro-inflammatory and procoagulant detrimental
      role in the vascular dysfunction of septic shock. It was the objective of this
      study to investigate mechanisms by which a pharmacological modulation of
      microparticles could affect vascular dysfunction in a rat model of septic shock.
      Septic or sham rats were treated by activated protein C (aPC) and resuscitated
      during 4 hours. Their microparticles were harvested and inoculated to another set
      of healthy recipient rats. Haemodynamic parameters were monitored, circulating
      total procoagulant microparticles assessed by prothrombinase assay, and their
      cell origin characterised. Mesenteric resistance arteries, aorta and heart were
      harvested for western blotting analysis. We found that a) the amount and
      phenotype of circulating microparticles were altered in septic rats with an
      enhanced endothelial, leucocyte and platelet contribution; b) aPC treatment
      significantly reduced the generation of leucocyte microparticles and
      norepinephrine requirements to reach the mean arterial pressure target in septic
      rats; c) Microparticles from untreated septic rats, but not from aPC-treated
      ones, significantly reduced the healthy recipients' mean arterial pressure; d)
      Microparticle thromboxane content and aPC activity were significantly increased
      in aPC-treated septic rats. In inoculated naive recipients, microparticles from
      aPC-treated septic rats prompted reduced NF-kappaB and cyclooxygenase-2 arterial
      activation, blunted the generation of pro-inflammatory iNOS and secondarily
      increased platelet and endothelial microparticles. In conclusion, in this septic
      shock model, increased circulating levels of procoagulant microparticles led to
      negative haemodynamic outcomes. Pharmacological treatment by aPC modified the
      cell origin and levels of circulating microparticles, thereby limiting vascular
      inflammation and favouring haemodynamic improvement. 

PMID- 24108661
TI  - Gene signature of the embryonic meniscus.
AB  - The meniscus is a fibrocartilagenous disc in the knee that protects the joint
      from damage. Meniscal injuries are common, however repair efforts are largely
      unsuccessful and are not able to prevent the degenerative changes that result in
      development of osteoarthritis. Tissue regeneration in adults often recapitulates
      events of embryonic development, suggesting the regulatory pathways controlling
      morphogenesis are candidate repair signals. Here we use laser capture
      microdissection to collect mouse embryonic day 16 (E16) meniscus, articular
      cartilage, and cruciate ligaments. RNA isolated from these tissues was then used
      to perform genome-wide microarray analysis. We found 38 genes were differentially
      expressed between E16 meniscus and articular cartilage and 43 genes were
      differentially expressed between E16 meniscus and cruciate ligaments. Included in
      our data set were extracellular matrix proteins, transcription factors, and
      growth factors, including TGF-beta modulators (Lox, Dpt) and IGF-1 pathway
      members (Igf-1, Igfbp2, Igfbp3, Igfbp5). Ingenuity Pathway Analysis revealed that
      IGF-1 signaling was enriched in the meniscus compared to the other joint
      structures, while qPCR showed that Igf-1, Igfbp2, and Igfbp3 expression declined
      with age. We also found that several meniscus-enriched genes were expressed
      either in the inner or outer meniscus, establishing that regionalization of the
      meniscus occurs early in development.

PMID- 24108662
TI  - Prevalence and risk factors for musculoskeletal problems associated with
      microlaryngeal surgery: a national survey.
AB  - OBJECTIVES/HYPOTHESIS: Microlaryngeal surgery (MLS) presents ergonomic challenges
      to surgeons and potential risks for developing musculoskeletal symptoms (MSSx).
      This study describes prevalence and risk factors of MLS-associated MSSx. STUDY
      DESIGN: Cross-sectional survey. METHODS: A questionnaire was administered to
      members of the American Academy of Otolaryngology-Head and Neck Surgery. Outcome
      measures related to surgeon demographics, training, MLS experience, operating
      room setup, experience of MSSx in relation to MLS, treatment sought, and practice
      changes due to MSSx. RESULTS: Response rate was 9.2% (n = 476); 83% reported
      musculoskeletal symptoms during MLS, and 21% reported rest breaks during MLS.
      Taking breaks was independently associated with back support lack (odds ratio
      [OR] = 2.08) and surgery lasting >30 minutes (OR = 1.68). Areas most commonly
      affected were neck, upper back, shoulder, and lower back. Ten percent reported
      treatment for MLS-related MSSx. Some respondents reported major practice changes
      due to MSSx, including fewer cases, ceasing to perform MLS, applying for
      disability, and early retirement. CONCLUSIONS: Musculoskeletal symptoms are
      common (83%) among surgeons performing microlaryngeal surgery. Findings suggest
      multiple factors may contribute to development of MSSx in otolaryngologists. Risk
      factors for MSSx and taking breaks during surgery include average case operating
      time >30 minutes and absence of back support. Previous studies have identified
      neck flexion and lack of arm support as associated with risk of musculoskeletal
      injury. This study demonstrates that MSSx related to surgery do occur in
      otolaryngologists, and that poor surgical ergonomics may play a role. Surgeons
      should consider proper support and positioning during MLS to protect their
      health.

PMID- 24108663
TI  - Utilizing two-dimensional ultrasound to develop normative curves for estimated
      placental volume.
AB  - OBJECTIVE: The objective of this study was to use two-dimensional (2D) ultrasound
      (US) during routine prenatal surveillance to develop normative estimated
      placental volume (EPV) growth curves. STUDY DESIGN: Patients >= 18 years old with
      singleton pregnancies were prospectively followed from 11 weeks gestational age
      (GA) until delivery. At routine US visits, placental width, height, and thickness
      were measured and EPV calculated using a validated mathematical model. RESULTS:
      In this study, 423 patients were scanned between 9.7 and 39.3 weeks GA to
      generate a total of 627 EPV calculations. Readings were clustered at 12 and 20
      weeks, times of routine scanning. The mean EPV was 73 +/- 47 cc at 12.5 +/- 1.5
      weeks (n = 444) and 276 +/- 106 cc at 20 +/- 2 weeks (n = 151). The data best fit
      a parabolic function as follows: EPV = (0.384GA - 0.00366GA(2))(3). Tenth and
      90th percentile lines were generated with +/- 1.28 SE offset. EPV readings below
      the 10th or above the 90th percentiles tended to be associated with either small
      or large newborns, respectively. CONCLUSION: Routine 2D US created EPV growth
      curves, which may be useful for stratifying patients into prenatal risk groups.

PMID- 24108664
TI  - Fetal thrombotic vasculopathy and perinatal thrombosis: should all placentas be
      examined?
AB  - OBJECTIVE: Numerous fetal placenta vascular lesions seem to be a predisposing
      condition for some types of perinatal disease. Placental disease and newborn
      thromboses might be both manifestations of the same underlying disorder.
      Objective of this study is to describe pathological lesions of the placenta in
      newborns with perinatal thrombosis. STUDY DESIGN: We present retrospective data
      review and analysis regarding neonates admitted at our neonatal intensive care
      unit and diagnosed with an episode of thromboembolic events (TE) in the period
      from 2009 to 2013; among them we report three cases of perinatal thrombosis in
      newborns whose placentas demonstrated fetal thrombotic vasculopathy (FTV).
      RESULTS: In all the three cases a prothrombotic maternal condition was found, and
      in one patient a maternal infection with chorioamnionitis; the histological
      examination of placenta, required soon after birth for maternal pathological
      conditions, was important in confirming and explaining the clinical diagnosis of
      neonatal thrombosis and for the management of future pregnancies. CONCLUSION: It
      is proposed that placenta of newborns with TE in first days of life should always
      be examined, for its association with FTV and thus the storage of placentas for a
      week after birth should be routinely implemented.

PMID- 24108665
TI  - Oliguria during hydrocortisone dosage wean in very low birth weight infants.
AB  - BACKGROUND: Intravenous hydrocortisone (HC) is often used in very low birth
      weight infants (VLBW) but can be complicated by oliguria when discontinued or
      tapered. OBJECTIVES: To determine which factors were associated with oliguria
      during HC taper. METHODS: We reviewed all VLBW infants who received initial doses
      of HC >= 1 mg/kg/d. The initial dose and duration of HC, and the incidence of
      oliguria (urine output [UO] < 2 mL/kg/h) during HC taper, were recorded. In those
      with oliguria, we recorded the change in UO (mL/kg/h), blood pressure, and
      creatinine. RESULTS: The mean initial HC dose was 2.8 +/- 1 mg/kg/d, and the mean
      total duration of HC therapy was 23 +/- 25 days. Oliguria occurred in 24% (13/54)
      of treated infants. These infants were exposed to higher and longer duration of
      the initial HC dose than infants without oliguria. Oliguria was predicted by the
      initial HC dose (odds ratio [OR] 5.8, 95% confidence interval [CI] 1.3-25.8, p =
      0.02) and by the number of days at initial dose (OR 1.7, 95%CI 1.1-2.7, p =
      0.03). CONCLUSIONS: Oliguria during HC dosage weaning was associated with higher
      initial HC exposure.

PMID- 24108666
TI  - Investigating the balance of reporting maternal and infant outcomes in pregnancy
      and childbirth Cochrane reviews.
AB  - OBJECTIVE: To summarize the overall conclusions of Cochrane Pregnancy and
      Childbirth Group (PCG) reviews where interventions have different effects on
      maternal and infant outcomes. METHODS: PCG reviews were analyzed and primary
      outcomes extracted and categorized by maternal and infant outcomes. The overall
      conclusions were categorized depending on whether they follow the benefit or harm
      for one group or are inconclusive due to the discrepancy. RESULTS: A total of 451
      current PCG reviews were assessed out of which 206 were analyzed. In general, the
      overall conclusions of reviews followed both beneficial and harmful outcomes.
      Around 58 (28.2%) recommended the intervention, 60 (29.1%) discouraged the
      intervention, and 88 (42.7%) were inconclusive. Total 10 Reviews reported
      opposing maternal and fetal/neonatal outcomes. Six (60%) contained inconclusive
      final recommendations. Three of the remaining four (75%) had a summary
      recommendation following the fetal/neonatal outcome. We did not detect bias based
      on whether the author group was obstetric or pediatric providers. CONCLUSION: The
      final author conclusions in PCG reviews generally follow the overall assessment
      of maternal and fetal/neonatal outcomes. There were, however, a large number of
      inconclusive final recommendations in PCG reviews. These findings highlight the
      fact that many interventions represent trade-offs between maternal and fetal
      outcomes.

PMID- 24108667
TI  - A targeted and FRET-based ratiometric fluorescent nanoprobe for imaging
      mitochondrial hydrogen peroxide in living cells.
AB  - Hydrogen peroxide (H2 O2 ) is a prominent member of the reactive oxygen species
      family and plays crucial roles in living organisms, thus detecting H2 O2 and
      elucidating its biological functions has become an important area of biological
      and biomedical research. Herein, a multifunctional fluorescent nanoprobe is
      demonstrated for detecting mitochondrial H2 O2 . The nanoprobe is prepared by
      covalently linking a mitochondria-targeting ligand (triphenylphosphonium, TPP)
      and a H2 O2 recognition element (PFl) onto carbon dots (CDs). For this nanoprobe,
      the CD serves as the carrier and the FRET donor. In the presence of H2 O2 , the
      PFl moieties on a CD undergo structural and spectral conversion, affording the
      nanoplatform a FRET-based ratiometric probe for H2 O2 . The nanoprobe displays
      excellent water dispersibility, high sensitivity and selectivity, satisfactory
      cell permeability, and very low cytotoxicity. Following the living cell uptake,
      this nanoprobe can specifically target and stain the mitochondria; and it can
      detect the exogenous H2 O2 in L929 cells, as well as the endogenously produced
      mitochondrial H2 O2 in Raw 264.7 cells upon stimulation by PMA. This study shows
      that CDs can serve as promising nano-carriers for fabricating practical
      multifunctional fluorescent nanosensors.

PMID- 24108669
TI  - Lone-pair...pi interaction: a rotational study of the chlorotrifluoroethylene
      water adduct.

PMID- 24108668
TI  - Phase 1 and pharmacodynamic trial of everolimus in combination with cetuximab in
      patients with advanced cancer.
AB  - BACKGROUND: Preclinical and clinical studies suggest mTOR (mammalian target of
      rapamycin) inhibitors may have metabolic and antiangiogenic effects, and
      synergize with epidermal growth factor pathway inhibitors. Therefore, a phase
      1/pharmacodynamic trial of everolimus with cetuximab was performed. METHODS: A
      total of 29 patients were randomized to a run-in of oral everolimus (30, 50, or
      70 mg) or cetuximab (400 mg/m(2) loading, 250 mg/m(2) maintenance) weekly,
      followed by the combination in this dose-escalation study. Primary endpoints were
      phase 2 dose and toxicity characterization. [(18)F]Fluorodeoxyglucose positron
      emission tomography (FDG-PET) was performed as a pharmacodynamic marker of mTOR
      inhibition, and dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI)
      was performed as an indicator of tumor perfusion changes, at 3 time points.
      RESULTS: Everolimus and cetuximab were tolerable at full doses, with an expected
      toxicity profile. Dose-limiting toxicities in the everolimus 70 mg group included
      grade 3 skin toxicity in 2 patients, and mucositis in 1 patient. Of 16 patients
      evaluable for response, 5 had stable disease lasting 4 to 19 months. Mean change
      in maximum standardized uptake value (SUV(max)) for those treated initially with
      everolimus was -24% (2% to -54%), and with cetuximab was -5% (-23 to 36%). The
      K(trans) measured by DCE-MRI did not decrease, regardless of run-in drug.
      CONCLUSIONS: Everolimus and cetuximab can be safely administered at standard
      doses, and are associated with prolonged disease control. The recommended phase 2
      dose of oral weekly everolimus is 70 mg in combination with standard cetuximab.
      Imaging studies reveal that metabolic inhibition by everolimus alone and in
      combination with cetuximab predominates over changes in tumor perfusion in this
      patient population.

PMID- 24108670
TI  - New reactions of N-tert-butylimines; formation of N-heterocycles by methyl
      radical elimination on flash vacuum thermolysis of N-benzylidene- and N-(2
      pyridylmethylidene)-tert-butylamines.
AB  - Thermal reactions of N-benzylidene- and N-(2-pyridylmethylidene)-tert-butylamines
      (5 and 13) under FVT conditions have been investigated. Unexpectedly, at 800 
      degrees C, compound 5 yields 1,2-dimethylindole and 3-methylisoquinoline. In the
      reaction of 13 at 800  degrees C, 3-methylimidazo[1,5-a]pyridine was obtained as
      the major product. Mechanisms of these reactions have been proposed on the basis
      of DFT calculations. Furthermore, UV-photoelectron spectroscopy combined with FVT
      has been applied for direct monitoring and characterization of the thermolysis
      products in situ. 

PMID- 24108671
TI  - Chitosan-based injectable hydrogel as a promising in situ forming scaffold for
      cartilage tissue engineering.
AB  - Chitosan-beta glycerophosphate-hydroxyethyl cellulose (CH-GP-HEC) is a
      biocompatible and biodegradable scaffold exhibiting a sol-gel transition at 37
      degrees C. Chondrogenic factors or mesenchymal stem cells (MSCs) can be included
      in the CH-GP-HEC, and injected into the site of injury to fill the cartilage
      tissue defects with minimal invasion and pain. The possible impact of the
      injectable CH-GP-HEC on the viability of the encapsulated MSCs was assessed by
      propidium iodide-fluorescein diacetate staining. Proliferation of the human and
      rat MSCs was also determined by MTS assay on days 0, 7, 14 and 28 after
      encapsulation. To investigate the potential application of CH-GP-HEC as a drug
      delivery device, the in vitro release profile of insulin was quantified by
      QuantiPro-BCATM protein assay. Chondrogenic differentiation capacity of the
      encapsulated human MSCs (hMSCs) was also determined after induction of
      differentiation with transforming growth factor beta3. MSCs have very good
      survival and proliferative rates within CH-GP-HEC hydrogel during the 28-day
      investigation. A sustained release of insulin occurred over 8 days. The CH-GP-HEC
      hydrogel also provided suitable conditions for chondrogenic differentiation of
      the encapsulated hMSCs. In conclusion, the high potential of CH-GP-HEC as an
      injectable hydrogel for cartilage tissue engineering is emphasised. 

PMID- 24108672
TI  - Juvenile nasopharyngeal angiofibroma resection: novel technique to improve
      posterior/inferior margin control.

PMID- 24108674
TI  - Social foragers adopt a riskier foraging mode in the centre of their groups.
AB  - Foraging in groups provides many benefits that are not necessarily experienced
      the same way by all individuals. I explore the possibility that foraging mode,
      the way individuals exploit resources, varies as a function of spatial position
      in the group, reflecting commonly occurring spatial differences in predation
      risk. I show that semipalmated sandpipers (Calidris pusilla), a social foraging
      avian species, tended to adopt a riskier foraging mode in the central, more
      protected areas of their groups. Central birds effectively used the more
      peripheral group members as sentinels, allowing them to exploit a wider range of
      resources within the same group at the same time. This finding provides a novel
      benefit of living in groups, which may have a broad relevance given that social
      foraging species often exploit a large array of resources. 

PMID- 24108673
TI  - Lack of ADAM10 in endothelial cells affects osteoclasts at the chondro-osseus
      junction.
AB  - Mice lacking ADAM10 in endothelial cells (Adam10DeltaEC mice) have shorter
      femurs, tibiae, and humeri than controls, raising questions about how endothelial
      cells could control long bone growth. We performed a histopathological evaluation
      of the femur and tibia growth plates at different postnatal stages, and assessed
      the distribution of TRAP-positive osteoclasts and endothelial cells at the growth
      plate. The growth plates in Adam10DeltaEC mice appeared normal at P7 and P14, but
      a thickened zone of hypertrophic chondrocytes and increased trabecular bone
      density were apparent by P21 and later. The number of TRAP+ cells at the COJ was
      normal at P7 and P14, but was strongly reduced at P21 and later. Moreover, the
      density of endomucin-stained endothelial cells at the COJ was increased starting
      at P7. The defects in long bone growth in Adam10DeltaEC mice could be caused by a
      lack of osteoclastogenesis at the COJ. Moreover, ADAM10 appears to regulate
      endothelial cell organization in the developing bone vasculature, perhaps in a
      similar manner as in the developing retinal vascular tree, where ADAM10 is
      thought to control Notch-dependent endothelial cell fate decisions. This study
      provides evidence for the regulation of osteoclast function by endothelial cells
      in vivo.

PMID- 24108675
TI  - Immune-priming in ant larvae: social immunity does not undermine individual
      immunity.
AB  - Social insects deploy numerous strategies against pathogens including
      behavioural, biochemical and immunological responses. While past research has
      revealed that adult social insects can generate immunity, few studies have
      focused on the immune function during an insect's early life stages. We
      hypothesized that larvae of the black carpenter ant Camponotus pennsylvanicus
      vaccinated with heat-killed Serratia marcescens should be less susceptible to a
      challenge with an active and otherwise lethal dose of the bacterium. We compared
      the in vivo benefits of prior vaccination of young larvae relative to naive and
      ringer injected controls. Regardless of colony of origin, survival parameters of
      vaccinated individuals following a challenge were significantly higher than those
      of the other two treatments. Results support the hypothesis that ant larvae
      exhibit immune-priming. Based on these results, we can infer that brood care by
      workers does not eliminate the need for individual-level immunological responses.
      Focusing on these early stages of development within social insect colonies can
      start addressing the complex dynamics between physiological (individual level)
      and social (collective) immunity. 

PMID- 24108676
TI  - The early bird gets the worm: foraging strategies of wild songbirds lead to the
      early discovery of food sources.
AB  - Animals need to manage the combined risks of predation and starvation in order to
      survive. Theoretical and empirical studies have shown that individuals can reduce
      predation risk by delaying feeding (and hence fat storage) until late afternoon.
      However, little is known about how individuals manage the opposing pressures of
      resource uncertainty and predation risks. We suggest that individuals should
      follow a two-part strategy: prioritizing the discovery of food early in the day
      and exploiting the best patch late in the day. Using automated data loggers, we
      tested whether a temporal component exists in the discovery of novel foraging
      locations by individuals in a mixed-species foraging guild. We found that food
      deployed in the morning was discovered significantly more often than food
      deployed in the afternoon. Based on the diurnal activity patterns in this
      population, overall rates of new arrivals were also significantly higher than
      expected in the morning and significantly lower than expected in the afternoon.
      These results align with our predictions of a shift from patch discovery to
      exploitation over the course of the day. 

PMID- 24108677
TI  - Detecting spring after a long winter: coma or slow vigilance in cold, hypoxic
      turtles?
AB  - Many freshwater turtle species can spend the winter submerged in ice-covered
      lakes by lowering their metabolism, and it has been proposed that such severe
      metabolic depression render these turtles comatose. This raises the question of
      how they can detect the arrival of spring and respond in a sensible way to
      sensory information during hibernation. Using evoked potentials from cold or
      hypoxic turtles exposed to vibration and light, we show that hibernating turtles
      maintain neural responsiveness to light stimuli during prolonged hypoxia.
      Furthermore, turtles held under hibernation conditions for 14 days increase their
      activity when exposed to light or elevated temperatures, but not to vibration or
      increased oxygen. It is concluded that hibernating turtles are not comatose, but
      remain vigilant during overwintering in cold hypoxia, allowing them to respond to
      the coming of spring and to adjust their behaviour to specific sensory inputs. 

PMID- 24108678
TI  - Polyaniline-coupled multifunctional 2D metal oxide/hydroxide graphene
      nanohybrids.

PMID- 24108679
TI  - Reply to colorectal carcinomas, KRAS p.G13D mutant allele-specific imbalance, and
      anti-epidermal growth factor receptor therapy.

PMID- 24108680
TI  - Design of glycosyltransferase inhibitors: pyridine as a pyrophosphate surrogate.
AB  - A series of ten glycosyltransferase inhibitors has been designed and synthesized
      by using pyridine as a pyrophosphate surrogate. The series was prepared by
      conjugation of carbohydrate, pyridine, and nucleoside building blocks by using a
      combination of glycosylation, the Staudinger-Vilarrasa amide-bond formation, and
      azide-alkyne click chemistry. The compounds were evaluated as inhibitors of five
      metal-dependent galactosyltransferases. Crystallographic analyses of three
      inhibitors complexed in the active site of one of the enzymes confirmed that the
      pyridine moiety chelates the Mn(2+) ion causing a slight displacement (2 A) from
      its original position. The carbohydrate head group occupies a different position
      than in the natural uridine diphosphate (UDP)-Gal substrate with little
      interaction with the enzyme.

PMID- 24108681
TI  - Preparing to work with big data in proteomics - a report on the HUPO-PSI Spring
      Workshop: April 15-17, 2013, Liverpool, UK.
AB  - The Human Proteome Organisation Proteomics Standards Initiative (HUPO-PSI) was
      established in 2002 with the aim of defining community standards for data
      representation in proteomics and facilitating data comparison, exchange and
      verification. The 2013 annual spring workshop was hosted by the University of
      Liverpool, UK and concentrated on updating and refining the existing standards in
      the light of new methodologies and technologies. To control the inflation of file
      sizes, strategies for file compression, particularly for mzML files, were
      explored. Best practices for encoding information such as protein grouping and
      PTM localisation were refined and documented. Additional example files for the
      mzQuantML format were designed to provide support for selected reaction
      monitoring techniques. Enhancements to the PSI Common Query Interface (PSICQUIC)
      and PSI-MI XML were discussed. Finally, the group engaged in discussion on how
      the existing work of the HUPO-PSI can be leveraged by the Metabolomics Standards
      Initiative to improve the capture of metabolite data.

PMID- 24108682
TI  - Early diagnosis of neurodegenerative diseases - the long awaited Holy Grail and
      bottleneck of modern brain research - 19th HUPO BPP workshop: May 22-24, 2013,
      Dortmund, Germany.
AB  - The HUPO Brain Proteome Project (HUPO BPP) held its 19th workshop in Dortmund,
      Germany, from May 22 to 24, 2013. The focus of the spring workshop was on
      strategies and developments concerning early diagnosis of neurodegenerative
      diseases.

PMID- 24108683
TI  - Multidimensional separation prior to mass spectrometry: getting closer to the
      bottom of the iceberg.
AB  - While prefractionation has previously been shown to improve results in MS
      analysis, a novel combination provides an additional dimension of separation:
      protein fractionation by SDS-PAGE followed by IEF of tryptic peptides before
      separation by RP-LC [Atanassov and Urlaub, Proteomics 2013, 13, 2947-2955]. This
      three-step separation procedure prior to MS/MS substantially increases proteome
      coverage and represents a further step toward a more comprehensive analysis of
      complex proteomes.

PMID- 24108688
TI  - At the intersection of math and reading disabilities: introduction to the special
      issue.
AB  - Individuals with comorbid disabilities in mathematics and reading face
      significant challenges in acquiring the componential skills related to each
      domain. Persons with these comorbid conditions are significantly understudied and
      this paucity of work limits how effective practitioners can be at addressing the
      needs of this population. In the United States, roughly 7% of all children suffer
      from math disability; of these, an estimated 17% to 66% also has a comorbid
      reading disability. Underspecification of current conceptualizations of math and
      reading disabilities, including how to best identify and classify individuals
      with one or more of these disabilities, hampers our efforts to intervene
      effectively. To conceptualize how to move forward in these areas, the Eunice
      Kennedy Shriver National Institute of Child Health and Human Development held a
      workshop focused on examining the etiology, classification, and remediation of
      comorbid math and reading disabilities. This special issue, titled At the
      Intersection of Math and Reading Disabilities, continues that discussion.
      Contributing authors articulate a path forward to address the needs of these
      learners and inform the foundational understanding of both conditions in
      isolation and as they interact. 

PMID- 24108690
TI  - Formation of two-dimensional supramolecular polymers by amphiphilic pyrene
      oligomers.
AB  - Reading the bands: Amphiphilic pyrene trimers self-assemble into two-dimensional,
      supramolecular polymers in aqueous medium. Folding and aggregation processes are
      accompanied by simultaneous development of J- and H-bands and significant changes
      in the fluorescence properties. The formation of sheet-like nano-structures is
      confirmed by AFM. 

PMID- 24108691
TI  - Fluorescent protein capped mesoporous nanoparticles for intracellular drug
      delivery and imaging.
AB  - A multifunctional system for intracellular drug delivery and simultaneous
      fluorescent imaging was constructed by using histidine-tagged, cyan fluorescent
      protein (CFP)-capped magnetic mesoporous silica nanoparticles (MMSNs). This
      protein-capped multifunctional nanostructure is highly biocompatible and does not
      affect cell viability or proliferation. The CFP acts not only as a capping agent,
      but also as a fluorescent imaging agent. The nanoassembly was activated by
      histidine-based replacement, leading to release of drug molecules encapsulated in
      the nanopores into the bulk solution. The fluorescent imaging functionality would
      allow noninvasive tracking of the nanoparticles in the body. By combining the
      drug delivery with cell-imaging capability, these nanoparticles may provide
      valuable multifunctional nanoplatforms for biomedical applications. 

PMID- 24108692
TI  - CLCN7 and TCIRG1 mutations differentially affect bone matrix mineralization in
      osteopetrotic individuals.
AB  - Osteopetrosis is an inherited disorder of impaired bone resorption, with the most
      commonly affected genes being CLCN7 and TCIRG1, encoding the Cl(-) /H(+)
      exchanger CLC-7 and the a3 subunit of the vacuolar H(+) -ATPase, respectively. We
      and others have previously shown that the disease is frequently accompanied by
      osteomalacia, and that this additional pathology is also found in Tcirg1
      deficient oc/oc mice. The remaining question was whether osteoid enrichment is
      specifically associated with TCIRG1 inactivation, or whether CLCN7 mutations
      would also cause skeletal mineralization defects. Here we describe a complete
      osteologic assessment of one family carrying a novel mutation in CLCN7 (D145G),
      which impairs the activation and relaxation kinetics of the CLC-7 ion
      transporter. The two siblings carrying the mutation in the homozygous state
      displayed high bone mass, increased serum levels of bone formation markers, but
      no impairment of calcium homeostasis when compared to the other family members.
      Most importantly, however, undecalcified processing of an iliac crest biopsy from
      one of the affected children clearly demonstrated a pathological increase of
      trabecular bone mass, but no signs of osteomalacia. Given the potential relevance
      of these findings we additionally performed undecalcified histology of iliac
      crest biopsies from seven additional cases with osteopetrosis caused by a
      mutation in TNFRSF11A (n=1), CLCN7 (n=3), or TCIRG1 (n=3). Here we observed that
      all cases with TCIRG1-dependent osteopetrosis displayed severe osteoid
      accumulation and decreased calcium content within the mineralized matrix. In
      contrast, there was no detectable bone mineralization defect in the cases with
      TNFRSF11A-dependent or CLCN7-dependent osteopetrosis. Taken together, our
      analysis demonstrates that CLCN7 and TCIRG1 mutations differentially affect bone
      matrix mineralization, and that there is a need to modify the current
      classification of osteopetrosis.

PMID- 24108693
TI  - Biphasic responses in multi-site phosphorylation systems.
AB  - Multi-site phosphorylation systems are repeatedly encountered in cellular biology
      and multi-site modification is a basic building block of post-translational
      modification. In this paper, we demonstrate how distributive multi-site
      modification mechanisms by a single kinase/phosphatase pair can lead to
      biphasic/partial biphasic dose-response characteristics for the maximally
      phosphorylated substrate at steady state. We use simulations and analysis to
      uncover a hidden competing effect which is responsible for this and analyse how
      it may be accentuated. We build on this to analyse different variants of multi
      site phosphorylation mechanisms showing that some mechanisms are intrinsically
      not capable of displaying this behaviour. This provides both a consolidated
      understanding of how and under what conditions biphasic responses are obtained in
      multi-site phosphorylation and a basis for discriminating between different
      mechanisms based on this. We also demonstrate how this behaviour may be combined
      with other behaviour such as threshold and bistable responses, demonstrating the
      capacity of multi-site phosphorylation systems to act as complex molecular signal
      processors. 

PMID- 24108694
TI  - Subtoxic and toxic concentrations of benzene and toluene induce Nrf2-mediated
      antioxidative stress response and affect the central carbon metabolism in lung
      epithelial cells A549.
AB  - Since people in industrialized countries spend most of their time indoors, the
      effects of indoor contaminants such as volatile organic compounds become more and
      more relevant. Benzene and toluene are among the most abundant compounds in the
      highly heterogeneous group of indoor volatile organic compounds. In order to
      understand their effects on lung epithelial cells (A549) representing lung's
      first line of defense, we chose a global proteome and a targeted metabolome
      approach in order to detect adverse outcome pathways caused by exposure to
      benzene and toluene. Using a DIGE approach, 93 of 469 detected protein spots were
      found to be differentially expressed after exposure to benzene, and 79 of these
      spots were identified by MS. Pathway analysis revealed an enrichment of proteins
      involved in Nrf2-mediated and oxidative stress response
      glycolysis/gluconeogenesis. The occurrence of oxidative stress at nonacute toxic
      concentrations of benzene and toluene was confirmed by the upregulation of the
      stress related proteins NQO1 and SOD1. The changes in metabolism were validated
      by ion chromatography MS/MS analysis revealing significant changes of glucose-6
      phosphate, fructose-6-phosphate, 3-phosphoglycerate, and NADPH. The molecular
      alterations identified as a result of benzene and toluene exposure demonstrate
      the detrimental effect of nonacute toxic concentrations on lung epithelial cells.
      The data provided here will allow for a targeted validation in in vivo models. 

PMID- 24108695
TI  - Burden of respiratory viruses in patients with acute respiratory failure.
AB  - Respiratory viruses (RVs) are ubiquitous pathogens that represent a major cause
      of community-acquired pneumonia and chronic pulmonary diseases exacerbations.
      However, their contribution to acute respiratory failure events requiring
      intensive care unit admission in the era of rapid multiplex molecular assay
      deserves further evaluation. This study investigated the burden of viral
      infections in non immunocompromised patients admitted to the intensive care unit
      for acute respiratory failure using a multiplex molecular assay. Patients were
      investigated for RVs using immunofluoresence testing and a commercial multiplex
      molecular assay, and for bacteria using conventional culture. Half the patients
      (34/70, 49%) had a documented RVs infection. No other pathogen was found in 24
      (71%) patients. Viral infection was detected more frequently in patients with
      obstructive respiratory diseases (64% vs. 29%; P = 0.0075). Multiplex molecular
      assay should be considered as an usefull diagnostic tool in patients admitted to
      the intensive care unit with acute respiratory failure, especially those with
      acute exacerbations of chronic obstructive pulmonary disease and asthma.

PMID- 24108697
TI  - MAIT recognition of a stimulatory bacterial antigen bound to MR1.
AB  - MR1-restricted mucosal-associated invariant T (MAIT) cells represent a
      subpopulation of alphabeta T cells with innate-like properties and limited TCR
      diversity. MAIT cells are of interest because of their reactivity against
      bacterial and yeast species, suggesting that they play a role in defense against
      pathogenic microbes. Despite the advances in understanding MAIT cell biology, the
      molecular and structural basis behind their ability to detect MR1-Ag complexes is
      unclear. In this study, we present our structural and biochemical
      characterization of MAIT TCR engagement of MR1 presenting an Escherichia coli
      derived stimulatory ligand, rRL-6-CH2OH, previously found in Salmonella
      typhimurium. We show a clear enhancement of MAIT TCR binding to MR1 due to the
      presentation of this ligand. Our structure of a MAIT TCR/MR1/rRL-6-CH2OH complex
      shows an evolutionarily conserved binding orientation, with a clear role for both
      the CDR3alpha and CDR3beta loops in recognizing the rRL-6-CH2OH stimulatory
      ligand. We also present two additional xenoreactive MAIT TCR/MR1 complexes that
      recapitulate the docking orientation documented previously, despite having
      variation in the CDR2beta and CDR3beta loop sequences. Our data support a model
      by which MAIT TCRs engage MR1 in a conserved fashion, with their binding
      affinities modulated by the nature of the MR1-presented Ag or diversity
      introduced by alternate Vbeta usage or CDR3beta sequences. 

PMID- 24108696
TI  - Molecular basis of 9G4 B cell autoreactivity in human systemic lupus
      erythematosus.
AB  - 9G4(+) IgG Abs expand in systemic lupus erythematosus (SLE) in a disease-specific
      fashion and react with different lupus Ags including B cell Ags and apoptotic
      cells. Their shared use of VH4-34 represents a unique system to understand the
      molecular basis of lupus autoreactivity. In this study, a large panel of
      recombinant 9G4(+) mAbs from single naive and memory cells was generated and
      tested against B cells, apoptotic cells, and other Ags. Mutagenesis eliminated
      the framework-1 hydrophobic patch (HP) responsible for the 9G4 idiotype. The
      expression of the HP in unselected VH4-34 cells was assessed by deep sequencing.
      We found that 9G4 Abs recognize several Ags following two distinct structural
      patterns. B cell binding is dependent on the HP, whereas anti-nuclear Abs,
      apoptotic cells, and dsDNA binding are HP independent and correlate with
      positively charged H chain third CDR. The majority of mutated VH4-34 memory cells
      retain the HP, thereby suggesting selection by Ags that require this germline
      structure. Our findings show that the germline-encoded HP is compulsory for the
      anti-B cell reactivity largely associated with 9G4 Abs in SLE but is not required
      for reactivity against apoptotic cells, dsDNA, chromatin, anti-nuclear Abs, or
      cardiolipin. Given that the lupus memory compartment contains a majority of HP(+)
      VH4-34 cells but decreased B cell reactivity, additional HP-dependent Ags must
      participate in the selection of this compartment. This study represents the first
      analysis, to our knowledge, of VH-restricted autoreactive B cells specifically
      expanded in SLE and provides the foundation to understand the antigenic forces at
      play in this disease. 

PMID- 24108698
TI  - A distinct subpopulation of human NK cells restricts B cell transformation by
      EBV.
AB  - NK cells constitute the first line of defense against pathogens and transformed
      cells. They mature in secondary lymphoid organs, including tonsils, where common
      pathogens, such as EBV, enter the host and potentially imprint differentiating
      cells, which then patrol the body via the blood stream. Therefore, we set out to
      characterize a distinct human NK cell population in tonsils that produces high
      amounts of the immunomodulatory and antiviral cytokine IFN-gamma. We found that
      the tonsilar IFN-gamma(high) NK cell subset is
      CD56(bright)NKG2A(+)CD94(+)CD54(+)CD62L(-), is present in tonsils ex vivo and is
      more mature than other CD56(bright) NK cells in tonsils and less mature than
      other NK cells in blood, shows very low plasticity even after prolonged cytokine
      stimulation, accumulates in tonsils of EBV carriers, and is able to potently
      restrict EBV-induced transformation of B cells. Thus, we characterized a distinct
      and stable IFN-gamma(high) NK cell subpopulation that can specifically restrict
      malignant transformation of EBV-infected B cells. This subset should be exploited
      for future development of cell-based therapeutic approaches in EBV-associated
      malignancies. 

PMID- 24108699
TI  - Cutting edge: Smad2 and Smad4 regulate TGF-beta-mediated Il9 gene expression via
      EZH2 displacement.
AB  - IL-9 is a proallergic cytokine produced by a newly proposed Th cell subset, Th9.
      Th9 cells can be generated by treatment of naive T cells with TGF-beta and IL-4
      in vitro. However, it is still not clear how TGF-beta signaling regulates Th9
      differentiation. In this study, we demonstrate that Smad2 and Smad4, two
      transcriptional factors activated by TGF-beta signaling, are required for Th9
      differentiation in vitro. Deficiency of Smad2 or Smad4 in T cells resulted in
      impaired IL-9 expression, which was coincident with enrichment of repressive
      chromatin modification histone H3 K27 trimethylation and enhanced EZH2 binding to
      the Il9 locus. Pharmacologic inhibition of EZH2 partially rescued IL-9 production
      in Smad-deficient Th9 cells. Smad proteins may displace EZH2 directly from the
      Il9 locus, because Smad2 and Smad4 can bind EZH2. Our data shed light on the
      molecular mechanisms underlying Th9 cell differentiation, revealing that the TGF
      beta-Smad2/4-signaling pathway regulates IL-9 production through an epigenetic
      mechanism. 

PMID- 24108700
TI  - Antigen modulation confers protection to red blood cells from antibody through
      Fcgamma receptor ligation.
AB  - Autoantibodies and alloantibodies can damage self-tissue or transplanted tissues
      through either fixation of complement or ligation of FcgammaRs. Several pathways
      have been described that imbue self-tissues with resistance to damage from
      complement fixation, as a protective measure against damage from these Abs.
      However, it has been unclear whether parallel pathways exist to provide
      protection from FcgammaR ligation by bound Abs. In this article, we describe a
      novel pathway by which cell surface Ag is specifically decreased as a result of
      Ab binding (Ag modulation) to the extent of conferring protection to recognized
      cells from Fcgamma-dependent clearance. Moreover, the Ag modulation in this
      system requires FcgammaR ligation. Together, these findings provide unique
      evidence of self-protective pathways for FcgammaR-mediated Ab damage. 

PMID- 24108702
TI  - Specific splice variants are associated with Parkinson's disease.
AB  - BACKGROUND: Diagnosis of Parkinson's disease (PD) currently relies on assessment
      of motor symptoms. Recently, sensitive, specific, and readily available splice
      variant-specific biomarkers were identified in peripheral blood from participants
      in the Diagnostic and Prognostic Biomarkers in Parkinson Disease study. METHODS:
      Here we test for an association between candidate splice variant biomarkers and
      PD in blood of an independent population of cases and controls nested in the
      Harvard NeuroDiscovery Center Biomarker Study. RESULTS: Expression of 7 out of 13
      candidate biomarkers was dysregulated in whole cellular blood of patients with
      PD. CONCLUSIONS: These results support the view that differential expression of a
      subset of splice-variant markers in blood is associated with PD. Further
      evaluation in untreated, de novo patients and at-risk subjects is warranted.

PMID- 24108703
TI  - At the Bench: Preclinical rationale for exploiting NK cells and gammadelta T
      lymphocytes for the treatment of high-risk leukemias.
AB  - NK cells and gammadelta T lymphocytes display potent cytolytic activity against
      leukemias and CMV-infected cells and are thus, promising immune effector cells in
      the context of allo-HSCT. NK cells express HLA class I-specific inhibitory
      receptors and preferentially kill HLA class I(low) tumors or virus-infected
      cells. Killing occurs upon engagement of activating NKRs with ligands that are up
      regulated on tumors and infected cells. A similar activating receptor/ligand
      interaction strategy is used by gammadelta T cells, which in addition, use their
      TCRs for recognition of phosphorylated antigens and still largely undefined
      ligands on tumor cells. In the haploidentical allo-HSCT setting, alloreactive NK
      cells, derived from donor HSCs, can exert potent antileukemia activity and kill
      residual patient DCs and T cells, thus preventing GvHD and graft rejection.
      However, generation of KIR(+) alloreactive NK cells from HSCs requires many
      weeks, during which leukemia relapses, and life-threatening infections may occur.
      Importantly, mature NK cells and gammadelta T cells can control certain
      infectious agents efficiently, in particular, limit CMV reactivation, and
      infusion of such donor cells at the time of HSCT has been implemented.
      Development of novel, cell-based immunotherapies, allowing improved trafficking
      and better targeting, will endow NK cells and gammadelta T lymphocytes with
      enhanced anti-tumor activity, also making them key reagents for therapies against
      solid tumors. The clinical aspects of using NK cells and gammadelta T lymphocytes
      against hematological malignancies, including the allo-HSCT context, are reviewed
      in the related side-by-side paper by Locatelli and colleagues [1]. 

PMID- 24108701
TI  - Structure-based design of altered MHC class II-restricted peptide ligands with
      heterogeneous immunogenicity.
AB  - Insights gained from characterizing MHC-peptide-TCR interactions have held the
      promise that directed structural modifications can have predictable functional
      consequences. The ability to manipulate T cell reactivity synthetically or
      through genetic engineering might thus be translated into new therapies for
      common diseases such as cancer and autoimmune disorders. In the current study, we
      determined the crystal structure of HLA-DR4 in complex with the nonmutated
      dominant gp100 epitope gp10044-59, associated with many melanomas. Altered
      peptide ligands (APLs) were designed to enhance MHC binding and hence T cell
      recognition of gp100 in HLA-DR4(+) melanoma patients. Increased MHC binding of
      several APLs was observed, validating this approach biochemically. Nevertheless,
      heterogeneous preferences of CD4(+) T cells from several HLA-DR4(+) melanoma
      patients for different gp100 APLs suggested highly variable TCR usage, even among
      six patients who had been vaccinated against the wild-type gp100 peptide. This
      heterogeneity prevented the selection of an APL candidate for developing an
      improved generic gp100 vaccine in melanoma. Our results are consistent with the
      idea that even conservative changes in MHC anchor residues may result in subtle,
      yet crucial, effects on peptide contacts with the TCR or on peptide dynamics,
      such that alterations intended to enhance immunogenicity may be unpredictable or
      counterproductive. They also underscore a critical knowledge gap that needs to be
      filled before structural and in vitro observations can be used reliably to devise
      new immunotherapies for cancer and other disorders. 

PMID- 24108704
TI  - Tolerogenic dendritic cells: molecular and cellular mechanisms in
      transplantation.
AB  - During the discovery of mechanisms that govern immune activation and suppression,
      immune tolerance always came second in the scientific timeline. This has
      subsequently shaped the advances in the clinical translation of DC therapy
      protocols used for immunostimulation or immunosuppression. With several hundred
      clinical trials already registered within the U.S. National Institutes of Health
      for the use of DCs in cancer vaccination, only a few involve TolDCs for use as
      negative vaccines. However, as a result of the strong scientific rationale from
      preclinical and clinical trials, the use of negative vaccination in organ
      transplantation is likely on its way to reach the extent of the use of positive
      cancer vaccines in the future. As the underlying mechanisms emerge, the role of
      DCs in the induction of transplant tolerance is recognized unambiguously as
      central in the bidirectional communication with various types of immune cells.
      This is achieved by a complex interplay of numerous tolerogenic signals involving
      regulatory cytokines and other surface-bound or soluble inhibitory molecules
      associated with corresponding inhibitory signaling cascades. A detailed
      understanding of these processes will accelerate the advances of clinical
      immunologists in translating their knowledge from bench to bedside. In this
      review, we present the role of TolDCs as well as the most recent findings
      concerning associated molecular and cellular mechanisms that shape the balance
      between regulatory and effector immune responses during organ transplantation. 

PMID- 24108705
TI  - Grand challenges in mapping the human brain: NSF workshop report.
AB  - This report summarizes the outcomes of the NSF Workshop on Mapping and
      Engineering the Brain, held at Arlington, VA, during August 13-14, 2013. Three
      grand challenges were identified, including high spatiotemporal resolution
      neuroimaging, perturbation-based neuroimaging, and neuroimaging in naturalistic
      environments. It was highlighted that each grand challenge requires
      groundbreaking discoveries, enabling technologies, appropriate knowledge
      transfer, and multi- and transdisciplinary education and training for success. 

PMID- 24108706
TI  - Modeling the glucose sensor error.
AB  - Continuous glucose monitoring (CGM) sensors are portable devices, employed in the
      treatment of diabetes, able to measure glucose concentration in the interstitium
      almost continuously for several days. However, CGM sensors are not as accurate as
      standard blood glucose (BG) meters. Studies comparing CGM versus BG demonstrated
      that CGM is affected by distortion due to diffusion processes and by time-varying
      systematic under/overestimations due to calibrations and sensor drifts. In
      addition, measurement noise is also present in CGM data. A reliable model of the
      different components of CGM inaccuracy with respect to BG (briefly, "sensor
      error") is important in several applications, e.g., design of optimal digital
      filters for denoising of CGM data, real-time glucose prediction, insulin dosing,
      and artificial pancreas control algorithms. The aim of this paper is to propose
      an approach to describe CGM sensor error by exploiting n multiple simultaneous
      CGM recordings. The model of sensor error description includes a model of blood
      to-interstitial glucose diffusion process, a linear time-varying model to account
      for calibration and sensor drift-in-time, and an autoregressive model to describe
      the additive measurement noise. Model orders and parameters are identified from
      the n simultaneous CGM sensor recordings and BG references. While the model is
      applicable to any CGM sensor, here, it is used on a database of 36 datasets of
      type 1 diabetic adults in which n = 4 Dexcom SEVEN Plus CGM time series and
      frequent BG references were available simultaneously. Results demonstrates that
      multiple simultaneous sensor data and proper modeling allow dissecting the sensor
      error into its different components, distinguishing those related to physiology
      from those related to technology. 

PMID- 24108707
TI  - Predicting free-living energy expenditure using a miniaturized ear-worn sensor:
      an evaluation against doubly labeled water.
AB  - Accurate estimation of daily total energy expenditure (EE)is a prerequisite for
      assisted weight management and assessing certain health conditions. The use of
      wearable sensors for predicting free-living EE is challenged by consistent sensor
      placement, user compliance, and estimation methods used. This paper examines
      whether a single ear-worn accelerometer can be used for EE estimation under free
      living conditions.An EE prediction model as first derived and validated in a
      controlled setting using healthy subjects involving different physical
      activities. Ten different activities were assessed showing a tenfold cross
      validation error of 0.24. Furthermore, the EE prediction model shows a mean
      absolute deviation(MAD) below 1.2 metabolic equivalent of tasks. The same model
      was applied to a free-living setting with a different population for further
      validation. The results were compared against those derived from doubly labeled
      water. In free-living settings, the predicted daily EE has a correlation of 0.74,
      p 0.008, and a MAD of 272 kcal day. These results demonstrate that laboratory
      derived prediction models can be used to predict EE under free-living conditions
      [corrected].

PMID- 24108709
TI  - Accurate localization of in-body medical implants based on spatial sparsity.
AB  - Wearable and implantable wireless communication devices have in recent years
      gained increasing attention for medical diagnostics and therapeutics. In
      particular, wireless capsule endoscopy has become a popular method to visualize
      and diagnose the human gastrointestinal tract. Estimating the exact position of
      the capsule when each image is taken is a very critical issue in capsule
      endoscopy. Several approaches have been developed by researchers to estimate the
      capsule location. However, some unique challenges exist for in-body localization,
      such as the severe multipath issue caused by the boundaries of different organs,
      inconsistency of signal propagation velocity and path loss parameters inside the
      human body, and the regulatory restrictions on using high-bandwidth or high-power
      signals. In this paper, we propose a novel localization method based on spatial
      sparsity. We directly estimate the location of the capsule without going through
      the usual intermediate stage of first estimating time-of-arrival or received
      signal strength, and then a second stage of estimating the location. We
      demonstrate the accuracy of the proposed method through extensive Monte Carlo
      simulations for radio frequency emission signals within the required power and
      bandwidth range. The results show that the proposed method is effective and
      accurate, even in massive multipath conditions.

PMID- 24108708
TI  - Integration of network topological and connectivity properties for neuroimaging
      classification.
AB  - Rapid advances in neuroimaging techniques have provided an efficient and
      noninvasive way for exploring the structural and functional connectivity of the
      human brain. Quantitative measurement of abnormality of brain connectivity in
      patients with neurodegenerative diseases, such as mild cognitive impairment (MCI)
      and Alzheimer's disease (AD), have also been widely reported, especially at a
      group level. Recently, machine learning techniques have been applied to the study
      of AD and MCI, i.e., to identify the individuals with AD/MCI from the healthy
      controls (HCs). However, most existing methods focus on using only a single
      property of a connectivity network, although multiple network properties, such as
      local connectivity and global topological properties, can potentially be used. In
      this paper, by employing multikernel based approach, we propose a novel
      connectivity based framework to integrate multiple properties of connectivity
      network for improving the classification performance. Specifically, two different
      types of kernels (i.e., vector-based kernel and graph kernel) are used to
      quantify two different yet complementary properties of the network, i.e., local
      connectivity and global topological properties. Then, multikernel learning (MKL)
      technique is adopted to fuse these heterogeneous kernels for neuroimaging
      classification. We test the performance of our proposed method on two different
      data sets. First, we test it on the functional connectivity networks of 12 MCI
      and 25 HC subjects. The results show that our method achieves significant
      performance improvement over those using only one type of network property.
      Specifically, our method achieves a classification accuracy of 91.9%, which is
      10.8% better than those by single network-property-based methods. Then, we test
      our method for gender classification on a large set of functional connectivity
      networks with 133 infants scanned at birth, 1 year, and 2 years, also
      demonstrating very promising results.

PMID- 24108710
TI  - A Generalized Correlation-Based Model for Out-of-Plane Motion Estimation in
      Freehand Ultrasound.
AB  - A big challenge in sensorless image-based ultrasound tracking is in the out-of
      plane motion estimation. The correlation value of a specific model of speckle
      known as fully developed speckle (FDS) can be used to estimate the out-of-plane
      displacement. In real tissue, this kind of pattern is rare and the deviation of
      speckle pattern from the ideal FDS model diminishes the accuracy of the out-of
      plane motion estimation. In this paper a new method for estimation of the out-of
      plane motion is proposed. Firstly a closed-form mathematical derivation is
      provided for the correlation of two RF echo signal patches at different
      positions. A linear regression model of the ultrasound beam profile is proposed
      to account for the spatial variability of the ultrasound beam and enhance the
      accuracy of out-of-plane motion estimation in real tissue. The statistical model
      of speckle used here is based on the Rician-Inverse Gaussian (RiIG) stochastic
      process of the speckle formation, which can be considered as a generalized form
      of the K-distribution with richer parametrization. In this work, for the first
      time the second-order statistics of the RIG model is used for speckle tracking.
      This statistical model allows for derivation of a closed-form formulation for the
      correlation coefficient based on the statistical parameters of every patch. Since
      the effect of coherency is considered in the RiIG model, it increases the
      reliability of the out-of-plane motion estimation. The flexibility of the
      proposed method enables almost any patch through the whole image to be used for
      the purpose of displacement estimation. The method has been evaluated both on ex
      vivo and in vivo tissues in various experiments including out-of-plane rotation
      (tilt, yaw) and free-hand imaging. The overall outcome demonstrates the potential
      of the proposed method for in vivo tissues. 

PMID- 24108712
TI  - Investigation of the role of feature selection and weighted voting in random
      forests for 3-D volumetric segmentation.
AB  - This paper describes a novel 3-D segmentation technique posed within the Random
      Forests (RF) classification framework. Two improvements over the traditional RF
      framework are considered. Motivated by the high redundancy of feature selection
      in the traditional RF framework, the first contribution develops methods to
      improve voxel classification by selecting relatively "strong" features and
      neglecting "weak" ones. The second contribution involves weighting each tree in
      the forest during the testing stage, to provide an unbiased and more accurate
      decision than provided by the traditional RF. To demonstrate the improvement
      achieved by these enhancements, experimental validation is performed on adult
      brain MRI and 3-D fetal femoral ultrasound datasets. In a comparison of the new
      method with a traditional Random Forest, the new method showed a notable
      improvement in segmentation accuracy. We also compared the new method with other
      state-of-the-art techniques to place it in context of the current 3-D medical
      image segmentation literature. 

PMID- 24108711
TI  - A unified approach to diffusion direction sensitive slice registration and 3-D
      DTI reconstruction from moving fetal brain anatomy.
AB  - This paper presents an approach to 3-D diffusion tensor image (DTI)
      reconstruction from multi-slice diffusion weighted (DW) magnetic resonance
      imaging acquisitions of the moving fetal brain. Motion scatters the slice
      measurements in the spatial and spherical diffusion domain with respect to the
      underlying anatomy. Previous image registration techniques have been described to
      estimate the between slice fetal head motion, allowing the reconstruction of 3D a
      diffusion estimate on a regular grid using interpolation. We propose Approach to
      Unified Diffusion Sensitive Slice Alignment and Reconstruction (AUDiSSAR) that
      explicitly formulates a process for diffusion direction sensitive DW-slice-to-DTI
      volume alignment. This also incorporates image resolution modeling to iteratively
      deconvolve the effects of the imaging point spread function using the multiple
      views provided by thick slices acquired in different anatomical planes. The
      algorithm is implemented using a multi-resolution iterative scheme and multiple
      real and synthetic data are used to evaluate the performance of the technique. An
      accuracy experiment using synthetically created motion data of an adult head and
      an experiment using synthetic motion added to sedated fetal monkey dataset show a
      significant improvement in motion-trajectory estimation compared to current state
      of-the-art approaches. The performance of the method is then evaluated on
      challenging but clinically typical in utero fetal scans of four different human
      cases, showing improved rendition of cortical anatomy and extraction of white
      matter tracts. While the experimental work focuses on DTI reconstruction (second
      order tensor model), the proposed reconstruction framework can employ any 5-D
      diffusion volume model that can be represented by the spatial parameterizations
      of an orientation distribution function. 

PMID- 24108713
TI  - Automatic tuberculosis screening using chest radiographs.
AB  - Tuberculosis is a major health threat in many regions of the world. Opportunistic
      infections in immunocompromised HIV/AIDS patients and multi-drug-resistant
      bacterial strains have exacerbated the problem, while diagnosing tuberculosis
      still remains a challenge. When left undiagnosed and thus untreated, mortality
      rates of patients with tuberculosis are high. Standard diagnostics still rely on
      methods developed in the last century. They are slow and often unreliable. In an
      effort to reduce the burden of the disease, this paper presents our automated
      approach for detecting tuberculosis in conventional posteroanterior chest
      radiographs. We first extract the lung region using a graph cut segmentation
      method. For this lung region, we compute a set of texture and shape features,
      which enable the X-rays to be classified as normal or abnormal using a binary
      classifier. We measure the performance of our system on two datasets: a set
      collected by the tuberculosis control program of our local county's health
      department in the United States, and a set collected by Shenzhen Hospital, China.
      The proposed computer-aided diagnostic system for TB screening, which is ready
      for field deployment, achieves a performance that approaches the performance of
      human experts. We achieve an area under the ROC curve (AUC) of 87% (78.3%
      accuracy) for the first set, and an AUC of 90% (84% accuracy) for the second set.
      For the first set, we compare our system performance with the performance of
      radiologists. When trying not to miss any positive cases, radiologists achieve an
      accuracy of about 82% on this set, and their false positive rate is about half of
      our system's rate. 

PMID- 24108714
TI  - Harmonic motion microwave Doppler imaging: a simulation study using a simple
      breast model.
AB  - A hybrid method for tissue imaging using dielectric and elastic properties is
      proposed and investigated with simple bi-layered breast model. In this method,
      local harmonic motion is generated in the tissue using a focused ultrasound
      probe. A narrow-band microwave signal is transmitted to the tissue. The Doppler
      component of the scattered signal, which depends on the dielectric and elastic
      properties of the vibrating region, is sensed. A plane-wave spectrum technique is
      used together with reciprocity theorem for calculating the response of a
      vibrating electrically small spherical tumor in breast tissue. The effects of
      operating frequency, antenna alignment and distance, and tumor depth on the
      received signal are presented. The effect of harmonic motion frequency on the
      vibration amplitude and displacement distribution is investigated with mechanical
      simulations using the finite element method. The safety of the method is analyzed
      in terms of microwave and ultrasound exposure of the breast tissue. The results
      show that the method has a potential in detecting tumors inside fibro-glandular
      breast tissue. 

PMID- 24108715
TI  - Contrast enhancement based on layered difference representation of 2D histograms.
AB  - A novel contrast enhancement algorithm based on the layered difference
      representation of 2D histograms is proposed in this paper. We attempt to enhance
      image contrast by amplifying the gray-level differences between adjacent pixels.
      To this end, we obtain the 2D histogram h(k, k + l ) from an input image, which
      counts the pairs of adjacent pixels with gray-levels k and k + l , and represent
      the gray-level differences in a tree-like layered structure. Then, we formulate a
      constrained optimization problem based on the observation that the gray-level
      differences, occurring more frequently in the input image, should be more
      emphasized in the output image. We first solve the optimization problem to derive
      the transformation function at each layer. We then combine the transformation
      functions at all layers into the unified transformation function, which is used
      to map input gray-levels to output gray-levels. Experimental results demonstrate
      that the proposed algorithm enhances images efficiently in terms of both
      objective quality and subjective quality.

PMID- 24108716
TI  - Bayesian predictor combination for lossless image compression.
AB  - Adaptive predictor combination (APC) is a framework for combining multiple
      predictors for lossless image compression and is often at the core of state-of
      the-art algorithms. In this paper, a Bayesian parameter estimation scheme is
      proposed for APC. Extensive experiments using natural, medical, and remote
      sensing images of 8-16 bit/pixel have confirmed that the predictive performance
      is consistently better than that of APC for any combination of fixed predictors
      and with only a marginal increase in computational complexity. The predictive
      performance improves with every additional fixed predictor, a property that is
      not found in other predictor combination schemes studied in this paper. Analysis
      and simulation show that the performance of the proposed algorithm is not
      sensitive to the choice of hyper-parameters of the prior distributions.
      Furthermore, the proposed prediction scheme provides a theoretical justification
      for the error correction stage that is often included as part of a prediction
      process.

PMID- 24108718
TI  - 3D Materials image segmentation by 2D propagation: a graph-cut approach
      considering homomorphism.
AB  - Segmentation propagation, similar to tracking, is the problem of transferring a
      segmentation of an image to a neighboring image in a sequence. This problem is of
      particular importance to materials science, where the accurate segmentation of a
      series of 2D serial-sectioned images of multiple, contiguous 3D structures has
      important applications. Such structures may have distinct shape, appearance, and
      topology, which can be considered to improve segmentation accuracy. For example,
      some materials images may have structures with a specific shape or appearance in
      each serial section slice, which only changes minimally from slice to slice, and
      some materials may exhibit specific inter-structure topology that constrains
      their neighboring relations. Some of these properties have been individually
      incorporated to segment specific materials images in prior work. In this paper,
      we develop a propagation framework for materials image segmentation where each
      propagation is formulated as an optimal labeling problem that can be efficiently
      solved using the graph-cut algorithm. Our framework makes three key
      contributions: 1) a homomorphic propagation approach, which considers the
      consistency of region adjacency in the propagation; 2) incorporation of shape and
      appearance consistency in the propagation; and 3) a local non-homomorphism
      strategy to handle newly appearing and disappearing substructures during this
      propagation. To show the effectiveness of our framework, we conduct experiments
      on various 3D materials images, and compare the performance against several
      existing image segmentation methods.

PMID- 24108717
TI  - Statistical analysis of tongue images for feature extraction and diagnostics.
AB  - In this paper, an in-depth analysis on the statistical distribution
      characteristics of human tongue color that aims to propose a mathematically
      described tongue color space for diagnostic feature extraction is presented.
      Three characteristics of tongue color space, i.e., tongue color gamut that
      defines the range of colors, color centers of 12 tongue color categories, and
      color distribution of typical image features in the tongue color gamut, are
      elaborately investigated in this paper. Based on a large database, which contains
      over 9000 tongue images collected by a specially designed noncontact colorimetric
      imaging system using a digital camera, the tongue color gamut is established in
      the CIE chromaticity diagram by an innovatively proposed color gamut boundary
      descriptor using one-class SVM algorithm. Thereafter, centers of 12 tongue color
      categories are defined accordingly. Furthermore, color distributions of several
      typical tongue features, such as red points and petechial points, are obtained to
      build a relationship between the tongue color space and color distributions of
      various tongue features. With the obtained tongue color space, a new color
      feature extraction method is proposed for diagnostic classification purposes,
      with experimental results validating its effectiveness.

PMID- 24108719
TI  - Algorithms for transform selection in multiple-transform video compression.
AB  - With a proper transform, an image or motion-compensated residual can be
      represented quite accurately with a small fraction of the transform coefficients.
      This is referred to as the energy compaction property. When multiple transforms
      are used, selecting the best transform for each block that leads to the best
      energy compaction is difficult. In this paper, we develop two algorithms to solve
      this problem. The first algorithm, which is computationally simple, leads to a
      locally optimal solution. The second algorithm, which is more computationally
      intensive, gives a globally optimal solution. We discuss the algorithms and their
      performance. Two-dimensional discrete cosine transform (2D-DCT) and direction
      adaptive one-dimensional discrete cosine transforms (1D-DCTs) are used to
      evaluate the performance of our algorithms. Results obtained are consistent with
      their coding performance. As an application example of this paper, we apply our
      algorithm to evaluate the performance of a potential video compression system
      based on a very large number of transforms.

PMID- 24108720
TI  - The technologically integrated oncosimulator: combining multiscale cancer
      modeling with information technology in the in silico oncology context.
AB  - This paper outlines the major components and function of the technologically
      integrated oncosimulator developed primarily within the Advancing Clinico Genomic
      Trials on Cancer (ACGT) project. The Oncosimulator is defined as an information
      technology system simulating in vivo tumor response to therapeutic modalities
      within the clinical trial context. Chemotherapy in the neoadjuvant setting,
      according to two real clinical trials concerning nephroblastoma and breast
      cancer, has been considered. The spatiotemporal simulation module embedded in the
      Oncosimulator is based on the multiscale, predominantly top-down, discrete entity
      discrete event cancer simulation technique developed by the In Silico Oncology
      Group, National Technical University of Athens. The technology modules include
      multiscale data handling, image processing, invocation of code execution via a
      spreadsheet-inspired environment portal, execution of the code on the grid, and
      the visualization of the predictions. A refining scenario for the eventual
      coupling of the oncosimulator with immunological models is also presented.
      Parameter values have been adapted to multiscale clinical trial data in a
      consistent way, thus supporting the predictive potential of the oncosimulator.
      Indicative results demonstrating various aspects of the clinical adaptation and
      validation process are presented. Completion of these processes is expected to
      pave the way for the clinical translation of the system.

PMID- 24108721
TI  - Radial Basis Function Based Neural Network for Motion Detection in Dynamic
      Scenes.
AB  - Motion detection, the process which segments moving objects in video streams, is
      the first critical process and plays an important role in video surveillance
      systems. Dynamic scenes are commonly encountered in both indoor and outdoor
      situations and contain objects such as swaying trees, spouting fountains,
      rippling water, moving curtains, and so on. However, complete and accurate motion
      detection in dynamic scenes is often a challenging task. This paper presents a
      novel motion detection approach based on radial basis function artificial neural
      networks to accurately detect moving objects not only in dynamic scenes but also
      in static scenes. The proposed method involves two important modules: a
      multibackground generation module and a moving object detection module. The
      multibackground generation module effectively generates a flexible probabilistic
      model through an unsupervised learning process to fulfill the property of either
      dynamic background or static background. Next, the moving object detection module
      achieves complete and accurate detection of moving objects by only processing
      blocks that are highly likely to contain moving objects. This is accomplished by
      two procedures: the block alarm procedure and the object extraction procedure.
      The detection results of our method were evaluated by qualitative and
      quantitative comparisons with other state-of-the-art methods based on a wide
      range of natural video sequences. The overall results show that the proposed
      method substantially outperforms existing methods with Similarity and F1 accuracy
      rates of 69.37% and 65.50%, respectively. 

PMID- 24108722
TI  - Sample Subset Optimization Techniques for Imbalanced and Ensemble Learning
      Problems in Bioinformatics Applications.
AB  - Data sampling is a widely used technique in a broad range of machine learning
      problems. Traditional sampling approaches generally rely on random resampling
      from a given dataset. However, these approaches do not take into consideration
      additional information, such as sample quality and usefulness. We recently
      proposed a data sampling technique, called sample subset optimization (SSO). The
      SSO technique relies on a cross-validation procedure for identifying and
      selecting the most useful samples as subsets. In this paper, we describe the
      application of SSO techniques to imbalanced and ensemble learning problems,
      respectively. For imbalanced learning, the SSO technique is employed as an under
      sampling technique for identifying a subset of highly discriminative samples in
      the majority class. In ensemble learning, the SSO technique is utilized as a
      generic ensemble technique where multiple optimized subsets of samples from each
      class are selected for building an ensemble classifier. We demonstrate the
      utilities and advantages of the proposed techniques on a variety of
      bioinformatics applications where class imbalance, small sample size, and noisy
      data are prevalent. 

PMID- 24108723
TI  - Detection of moving objects using multi-channel kernel fuzzy correlogram based
      background subtraction.
AB  - In this paper, we examine the suitability of correlogram for background
      subtraction, as a step towards moving object detection. Correlogram captures
      inter-pixel relationships in a region and is seen to be effective for modeling
      the dynamic backgrounds. A multi-channel correlogram is proposed using inter
      channel and intra-channel correlograms to exploit full color information and the
      inter-pixel relations on the same color planes and across the planes. We
      thereafter derive a novel feature, termed multi-channel kernel fuzzy correlogram,
      composed by applying a fuzzy membership transformation over multi-channel
      correlogram. Multi-channel kernel fuzzy correlogram maps multi-channel
      correlogram into a reduced dimensionality space and is less sensitivity to noise.
      The approach handles multimodal distributions without using multiple models per
      pixel unlike traditional approaches. The approach does not require ideal
      background frames for background model initialization and can be initialized with
      moving objects also. Effectiveness of the proposed method is illustrated on
      different video sequences. 

PMID- 24108724
TI  - Dominance-based ranking functions for interval-valued intuitionistic fuzzy sets.
AB  - The ranking of interval-valued intuitionistic fuzzy sets (IvIFSs) is difficult
      since they include the interval values of membership and nonmembership. This
      paper proposes ranking functions for IvIFSs based on the dominance concept. The
      proposed ranking functions consider the degree to which an IvIFS dominates and is
      not dominated by other IvIFSs. Based on the bivariate framework and the dominance
      concept, the functions incorporate not only the boundary values of membership and
      nonmembership, but also the relative relations among IvIFSs in comparisons. The
      dominance-based ranking functions include bipolar evaluations with a parameter
      that allows the decision-maker to reflect his actual attitude in allocating the
      various kinds of dominance. The relationship for two IvIFSs that satisfy the dual
      couple is defined based on four proposed ranking functions. Importantly, the
      proposed ranking functions can achieve a full ranking for all IvIFSs. Two
      examples are used to demonstrate the applicability and distinctiveness of the
      proposed ranking functions. 

PMID- 24108725
TI  - How much control is enough? Influence of unreliable input on user experience.
AB  - Brain-computer interfaces (BCI) provide a valuable new input modality within
      human-computer interaction systems. However, like other body-based inputs such as
      gesture or gaze based systems, the system recognition of input commands is still
      far from perfect. This raises important questions, such as what level of control
      should such an interface be able to provide. What is the relationship between
      actual and perceived control? And in the case of applications for entertainment
      in which fun is an important part of user experience, should we even aim for the
      highest level of control, or is the optimum elsewhere? In this paper, we evaluate
      whether we can modulate the amount of control and if a game can be fun with less
      than perfect control. In the experiment users (n = 158) played a simple game in
      which a hamster has to be guided to the exit of a maze. The amount of control the
      user has over the hamster is varied. The variation of control through confusion
      matrices makes it possible to simulate the experience of using a BCI, while using
      the traditional keyboard for input. After each session the user completed a short
      questionnaire on user experience and perceived control. Analysis of the data
      showed that the perceived control of the user could largely be explained by the
      amount of control in the respective session. As expected, user frustration
      decreases with increasing control. Moreover, the results indicate that the
      relation between fun and control is not linear. Although at lower levels of
      control fun does increase with improved control, the level of fun drops just
      before perfect control is reached (with an optimum around 96%). This poses new
      insights for developers of games who want to incorporate some form of BCI or
      other modality with unreliable input in their game: for creating a fun game,
      unreliable input can be used to create a challenge for the user.

PMID- 24108726
TI  - Therapy for sepsis: Einstein once said...

PMID- 24108727
TI  - ARDS: progress unlikely with non-biological definition.

PMID- 24108728
TI  - Clinical guidelines and the question of uncertainty.

PMID- 24108729
TI  - Dorsal scapular nerve injury: a complication of ultrasound-guided interscalene
      block.

PMID- 24108730
TI  - Navigation-assisted peripherally inserted central catheter's insertion performed
      by university degree nurses: technical report of two cases.

PMID- 24108731
TI  - Training for tracheostomy.

PMID- 24108732
TI  - Pain management: a global perspective.

PMID- 24108733
TI  - Simulator for teaching hand-eye coordination during ultrasound-guided regional
      anaesthesia.

PMID- 24108734
TI  - Paediatric application of the EZ-Blocker for thoracoscopic sympathectomy.

PMID- 24108735
TI  - Quadriplegia after interscalene block for shoulder surgery in sitting position.

PMID- 24108736
TI  - Acupuncture for treatment of therapy-resistant post-dural puncture headache: a
      retrospective case series.

PMID- 24108744
TI  - ERK1/2 blockade prevents epithelial-mesenchymal transition in lung cancer cells
      and promotes their sensitivity to EGFR inhibition.
AB  - Overcoming cellular mechanisms of de novo and acquired resistance to drug therapy
      remains a central challenge in the clinical management of many cancers, including
      non-small cell lung cancer (NSCLC). Although much work has linked the epithelial
      mesenchymal transition (EMT) in cancer cells to the emergence of drug resistance,
      it is less clear where tractable routes may exist to reverse or inhibit EMT as a
      strategy for drug sensitization. Here, we demonstrate that extracellular signal
      regulated kinase (ERK) 1/2 (mitogen-activated protein kinase 3/1, MAPK3/1)
      signaling plays a key role in directing the mesenchymal character of NSCLC cells
      and that blocking ERK signaling is sufficient to heighten therapeutic responses
      to EGF receptor (EGFR) inhibitors. MEK1/2 (MAPKK1/2) inhibition promoted an
      epithelial phenotype in NSCLC cells, preventing induction of EMT by exogenous TGF
      beta. Moreover, in cells exhibiting de novo or acquired resistance to the EGFR
      inhibitor gefitinib, MEK inhibition enhanced the sensitivity to gefitinib and
      slowed cell migration. These effects only occurred, however, if MEK was inhibited
      for a period sufficient to trigger changes in EMT marker expression. Consistent
      with these findings, changes in EMT phenotypes and markers were also induced by
      the expression of mutant KRAS in a MEK-dependent manner. Our results suggest that
      prolonged exposure to MEK or ERK inhibitors may not only restrain EMT but also
      overcome naive or acquired resistance of NSCLC to EGFR-targeted therapy in the
      clinic.

PMID- 24108746
TI  - Induced current pharmacological split stimulation system for neuronal networks.
AB  - Magnetic stimulation noninvasively modulates neuronal activity through a
      magnetically induced current. However, despite the usefulness and popularity of
      this method, the effects of neuronal activity in the nonstimulated regions on the
      stimulus responses are unknown. Here, we report that the induced current-evoked
      responses were affected by neuronal activities in the nonstimulated regions. Our
      experiment used a Mu-metal-based localized induced current stimulation (LICS)
      system combined with the microfabricated cell culture chamber system and a
      microelectrode array (MEA). The cell culture chamber system has radiating
      microtunnels connecting one central and eight outer chambers, which were
      fabricated using soft lithography and a replica modeling technique with SU-8
      photoresist and polydimethylsiloxane (PDMS). Rat cortical neurons were separately
      cultured in the chambers and formed functional synaptic connections through the
      microtunnels. By applying a biphasic alternating pulsed magnetic field to the Mu
      metal located in the central chamber, induced currents were mainly generated near
      the cultured neurons and modified the neuronal activities, which were recorded
      through MEA. Furthermore, we confirmed that the evoked responses were modified by
      localized pharmacological stimulation (LPS) in the outer chambers. These results
      suggest that our system would be promising tool for analyzing the effect of
      magnetic stimulation on interacting neuronal activity.

PMID- 24108745
TI  - A Gerbode-like defect associated with Ebstein's anomaly in an adult patient.

PMID- 24108747
TI  - Advanced statistical matrices for texture characterization: application to cell
      classification.
AB  - This paper presents new structural statistical matrices which are gray level size
      zone matrix (SZM) texture descriptor variants. The SZM is based on the
      cooccurrences of size/intensity of each flat zone (connected pixels with the same
      gray level). The first improvement increases the information processed by merging
      multiple gray-level quantizations and reduces the required parameter numbers. New
      improved descriptors were especially designed for supervised cell texture
      classification. They are illustrated thanks to two different databases built from
      quantitative cell biology. The second alternative characterizes the DNA
      organization during the mitosis, according to zone intensities radial
      distribution. The third variant is a matrix structure generalization for the
      fibrous texture analysis, by changing the intensity/size pair into the
      length/orientation pair of each region. 

PMID- 24108748
TI  - Segmentation of high angular resolution diffusion MRI using sparse riemannian
      manifold clustering.
AB  - We address the problem of segmenting high angular resolution diffusion imaging
      (HARDI) data into multiple regions (or fiber tracts) with distinct diffusion
      properties. We use the orientation distribution function (ODF) to model diffusion
      and cast the ODF segmentation problem as a clustering problem in the space of
      ODFs. Our approach integrates tools from sparse representation theory and
      Riemannian geometry into a graph theoretic segmentation framework. By exploiting
      the Riemannian properties of the space of ODFs, we learn a sparse representation
      for each ODF and infer the segmentation by applying spectral clustering to a
      similarity matrix built from these representations. In cases where regions with
      similar (resp. distinct) diffusion properties belong to different (resp. same)
      fiber tracts, we obtain the segmentation by incorporating spatial and user
      specified pairwise relationships into the formulation. Experiments on synthetic
      data evaluate the sensitivity of our method to image noise and to the
      concentration parameters, and show its superior performance compared to
      alternative methods when analyzing complex fiber configurations. Experiments on
      phantom and real data demonstrate the accuracy of the proposed method in
      segmenting simulated fibers and white matter fiber tracts of clinical importance.

PMID- 24108749
TI  - Multi-part modeling and segmentation of left atrium in C-arm CT for image-guided
      ablation of atrial fibrillation.
AB  - As a minimally invasive surgery to treat atrial fibrillation (AF), catheter based
      ablation uses high radio-frequency energy to eliminate potential sources of
      abnormal electrical events, especially around the ostia of pulmonary veins (PV).
      Fusing a patient-specific left atrium (LA) model (including LA chamber,
      appendage, and PVs) with electro-anatomical maps or overlaying the model onto 2-D
      real-time fluoroscopic images provides valuable visual guidance during the
      intervention. In this work, we present a fully automatic LA segmentation system
      on nongated C-arm computed tomography (C-arm CT) data, where thin boundaries
      between the LA and surrounding tissues are often blurred due to the cardiac
      motion artifacts. To avoid segmentation leakage, the shape prior should be
      exploited to guide the segmentation. A single holistic shape model is often not
      accurate enough to represent the whole LA shape population under anatomical
      variations, e.g., the left common PVs vs. separate left PVs. Instead, a part
      based LA model is proposed, which includes the chamber, appendage, four major
      PVs, and right middle PVs. Each part is a much simpler anatomical structure
      compared to the holistic one and can be segmented using a model-based approach
      (except the right middle PVs). After segmenting the LA parts, the gaps and
      overlaps among the parts are resolved and segmentation of the ostia region is
      further refined. As a common anatomical variation, some patients may contain
      extra right middle PVs, which are segmented using a graph cuts algorithm under
      the constraints from the already extracted major right PVs. Our approach is
      computationally efficient, taking about 2.6 s to process a volume with 256 * 256
      * 245 voxels. Experiments on 687 C-arm CT datasets demonstrate its robustness and
      state-of-the-art segmentation accuracy. 

PMID- 24108750
TI  - Simulation of the expected performance of a seamless scanner for brain PET based
      on highly pixelated CdTe detectors.
AB  - The aim of this work is the evaluation of the design for a nonconventional PET
      scanner, the voxel imaging PET (VIP), based on pixelated room-temperature CdTe
      detectors yielding a true 3-D impact point with a density of 450 channels/cm(3),
      for a total 6 336 000 channels in a seamless ring shaped volume. The system is
      simulated and evaluated following the prescriptions of the NEMA NU 2-2001 and the
      NEMA NU 4-2008 standards. Results show that the excellent energy resolution of
      the CdTe detectors (1.6% for 511 keV photons), together with the small voxel
      pitch (1 * 1 * 2 mm(3)), and the crack-free ring geometry, give the design the
      potential to overcome the current limitations of PET scanners and to approach the
      intrinsic image resolution limits set by physics. The VIP is expected to reach a
      competitive sensitivity and a superior signal purity with respect to values
      commonly quoted for state-of-the-art scintillating crystal PETs. The system can
      provide 14 cps/kBq with a scatter fraction of 3.95% and 21 cps/kBq with a scatter
      fraction of 0.73% according to NEMA NU 2-2001 and NEMA NU 4-2008, respectively.
      The calculated NEC curve has a peak value of 122 kcps at 5.3 kBq/mL for NEMA NU 2
      2001 and 908 kcps at 1.6 MBq/mL for NEMA NU 4-2008. The proposed scanner can
      achieve an image resolution of ~ 1 mm full-width at half-maximum in all
      directions. The virtually noise-free data sample leads to direct positive impact
      on the quality of the reconstructed images. As a consequence, high-quality high
      resolution images can be obtained with significantly lower number of events
      compared to conventional scanners. Overall, simulation results suggest the VIP
      scanner can be operated either at normal dose for fast scanning and high patient
      throughput, or at low dose to decrease the patient radioactivity exposure. The
      design evaluation presented in this work is driving the development and the
      optimization of a fully operative prototype to prove the feasibility of the VIP
      concept. 

PMID- 24108751
TI  - Sit-to-stand measurement for in-home monitoring using voxel analysis.
AB  - We present algorithms to segment the activities of sitting and standing, and
      identify the regions of sit-to-stand (STS) transitions in a given image sequence.
      As a means of fall risk assessment, we propose methods to measure STS time using
      the 3-D modeling of a human body in voxel space as well as ellipse fitting
      algorithms and image features to capture orientation of the body. The proposed
      algorithms were tested on ten older adults with ages ranging from 83 to 97. Two
      techniques in combination yielded the best results, namely the voxel height in
      conjunction with the ellipse fit. Accurate STS time was computed on various STSs
      and verified using a marker-based motion capture system. This application can be
      used as part of a continuous video monitoring system in the homes of older adults
      and can provide valuable information to help detect fall risk and enable early
      interventions. 

PMID- 24108752
TI  - Supervised hierarchical Bayesian model-based electomyographic control and
      analysis.
AB  - This work suggests a supervised hierarchical Bayesian model for surface
      electromyography (sEMG)-based motion classification and its strategy analysis.
      The proposed model unifies the optimal feature extraction and classification
      through probabilistic inference and learning by identifying the latent neural
      states (LNSs) that govern a collection of sEMG signals. In addition, the
      inference step provides an approach to identify distinct muscle activation
      strategies according to sEMG patterns based on LNSs. To validate the model, nine
      class classification using four sEMG sensors on the limb motions is tested. The
      model performance is evaluated with relatively high and low activation levels,
      generalized classification across subjects and online classification. The model,
      based on LNSs to capture various motions, is assessed with respect to activation
      levels, individual subjects and transition during online classification. Our
      approach cannot only classify sEMG patterns, but also provide the interpretation
      of sEMG strategic patterns. This work supports the potential of the proposed
      model for sEMG control-based applications.

PMID- 24108753
TI  - A three-step multimodal analysis framework for modeling corticomuscular activity
      with application to Parkinson's disease.
AB  - Corticomuscular coupling analysis based on multiple datasets such as
      electroencephalography (EEG) and electromyography (EMG) signals provides a useful
      tool for understanding human motor control systems. A popular conventional method
      to assess corticomuscular coupling has been the pair-wise magnitude-squared
      coherence (MSC) between EEG and concomitant EMG recordings. However, there are
      certain limitations associated with the MSC, including the difficulty in robustly
      assessing group inference, only dealing with two types of datasets simultaneously
      and the biologically implausible assumption of pair-wise interactions. To
      overcome such limitations, in this paper, we propose assessing corticomuscular
      coupling by combining multiset canonical correlation analysis (M-CCA) and joint
      independent component analysis (jICA). The proposed method takes advantage of the
      M-CCA and jICA to ensure that the extracted components are maximally correlated
      across multiple datasets and meanwhile statistically independent within each
      dataset. Simulations were performed to illustrate the performance of the proposed
      method. We also applied the proposed method to concurrent EEG, EMG, and behavior
      data collected in a Parkinson's disease (PD) study. The results reveal highly
      correlated temporal patterns among the three types of signals and corresponding
      spatial activation patterns. In addition to the expected motor areas, the
      corresponding spatial activation patterns demonstrate enhanced occipital
      connectivity in the PD subjects, consistent with previous medical findings.

PMID- 24108754
TI  - Sleep and wake classification with actigraphy and respiratory effort using
      dynamic warping.
AB  - This paper proposes the use of dynamic warping (DW) methods for improving
      automatic sleep and wake classification using actigraphy and respiratory effort.
      DW is an algorithm that finds an optimal nonlinear alignment between two series
      allowing scaling and shifting. It is widely used to quantify (dis)similarity
      between two series. To compare the respiratory effort between sleep and wake
      states by means of (dis)similarity, we constructed two novel features based on
      DW. For a given epoch of a respiratory effort recording, the features search for
      the optimally aligned epoch within the same recording in time and frequency
      domain. This is expected to yield a high (or low) similarity score when this
      epoch is sleep (or wake). Since the comparison occurs throughout the entire-night
      recording of a subject, it may reduce the effects of within- and between-subject
      variations of the respiratory effort, and thus help discriminate between sleep
      and wake states. The DW-based features were evaluated using a linear discriminant
      classifier on a dataset of 15 healthy subjects. Results show that the DW-based
      features can provide a Cohen's Kappa coefficient of agreement kappa = 0.59 which
      is significantly higher than the existing respiratory-based features and is
      comparable to actigraphy. After combining the actigraphy and the DW-based
      features, the classifier achieved a kappa of 0.66 and an overall accuracy of
      95.7%, outperforming an earlier actigraphy- and respiratory-based feature set (
      kappa = 0.62). The results are also comparable with those obtained using an
      actigraphy- and cardiorespiratory-based feature set but have the important
      advantage that they do not require an ECG signal to be recorded.

PMID- 24108755
TI  - A cluster-based differential evolution with self-adaptive strategy for multimodal
      optimization.
AB  - Multimodal optimization is one of the most challenging tasks for optimization. It
      requires an algorithm to effectively locate multiple global and local optima, not
      just single optimum as in a single objective global optimization problem. To
      address this objective, this paper first investigates a cluster-based
      differential evolution (DE) for multimodal optimization problems. The clustering
      partition is used to divide the whole population into subpopulations so that
      different subpopulations can locate different optima. Furthermore, the self
      adaptive parameter control is employed to enhance the search ability of DE. In
      this paper, the proposed multipopulation strategy and the self-adaptive parameter
      control technique are applied to two versions of DE, crowding DE (CDE) and
      species-based DE (SDE), which yield self-CCDE and self-CSDE, respectively. The
      new algorithms are tested on two different sets of benchmark functions and are
      compared with several state-of-the-art designs. The experiment results
      demonstrate the effectiveness and efficiency of the proposed multipopulation
      strategy and the self-adaptive parameter control technique. The proposed
      algorithms consistently rank top among all the competing state-of-the-art
      algorithms. 

PMID- 24108756
TI  - Association of mitral annular calcification with endothelial dysfunction, carotid
      intima-media thickness and serum fetuin-A: an observational study.
AB  - OBJECTIVE: Mitral annular calcification (MAC) is characterized by degenerative
      calcification of the mitral valve annulus. Atherosclerosis plays role in
      progression of MAC. Fetuin A is the inhibitor of pathological calcification. In
      the present study, we investigated the relationship between MAC and fetuin A with
      carotid intima media thickness (CIMT) and endothelial dysfunction. METHODS: In
      this observational cross-sectional study, 40 patients with documented MAC on
      transthoracic echocardiography and 40 without MAC were included. All patients had
      coronary artery disease (CAD). Endothelial functions were assessed by brachial
      artery Doppler ultrasound (USG) and carotid artery Doppler USG. Serum fetuin-A
      level was also measured. Linear regression analysis and receiver operator curve
      analysis were performed. RESULTS: Endothelial derived vasodilatory response
      (EDVR) was significantly decreased and CIMT value was increased in MAC group.
      There was a strong positive correlation between EDVR and serum fetuin-A value.
      There was a strong negative correlation between CIMT and EDVR, moderately
      negative correlation between CIMT and serum fetuin-A level. Simple linear
      regression analysis revealed that CIMT (beta=0.367, p=0.001) and serum fetuin-A
      level (beta=-0.291, p=0.009) were independent factors associated with MAC. The
      area under the curve (AUC) for serum fetuin-A level was 0.731 (95% 0.620-0.824)
      and AUC for CIMT was 0.724 (95% CI 0.613-0.818). CONCLUSION: We observed that MAC
      is closely related with CIMT and serum fetuin-A level. Serum fetuin-A and CIMT
      can be used as independent markers in the diagnosis of MAC. We suggest that MAC
      can be used as an early determinant of CAD.

PMID- 24108757
TI  - The relationship between gamma-glutamyltransferase and coronary collateral
      circulation in patients with chronic total occlusion.
AB  - OBJECTIVE: The aim of this study was to evaluate the relation between blood gamma
      glutamyltransferase (GGT) levels and coronary collateral circulation in patients
      with chronic total occlusion (CTO). METHODS: Two hundred twenty-two patients with
      chronic stable coronary artery disease (CAD) and CTO were included in this cross
      sectional, observational study. Coronary collaterals were graded from 0 to 3
      according to the Rentrop method. Patients with grade 0-1 collateral development
      were regarded as poor collateral group (n=66) while patients with grade 2-3
      collateral development were regarded as good collateral group (n=156).
      Statistical analysis was performed using independent samples t, Mann-Whitney U
      and Chi-square tests, logistic regression and receiver operator curve analysis.
      RESULTS: The poor coronary collateral group had significantly higher levels of
      serum GGT compared to the good collateral group (p<0.001). Multiple logistic
      regression analysis showed that GGT levels were independent predictors of poor
      collateral circulation (OR-0.946, 95% CI=0.918-0.9719, p<0.001). The result of
      ROC curve analysis for GGT was as following: area under the ROC curve
      (AUC)=0.732, 95% CI: 0.622-0.841, p<0.001. CONCLUSION: Higher GGT levels are
      associated with poor coronary collateral circulation in patients with CTO. GGT
      may be used to predict the grade of coronary collateral circulation in CTO
      patients with chronic stable CAD.

PMID- 24108758
TI  - Pre-ictal heart rate variability assessment of epileptic seizures by means of
      linear and non-linear analyses.
AB  - OBJECTIVE: The purpose of the present study was to analyze the effects of
      epilepsy on the autonomic control of the heart in pre-ictal phase in order to
      find an algorithm of early detection of seizure onset. METHODS: Overall 133
      epileptic seizures were analyzed from 12 patients with epilepsy (seven males and
      five females; mean age 43.91 years, SD: 10.16) participated in this study. Single
      lead electrocardiogram recordings of epileptic patients were compiled. 240, 90
      30, 30-10 and 5 minutes heart rate variability (HRV) signals of preseizure were
      chosen for analysis of heart rate. As HRV signals are non-stationary, a set of
      time and frequency domain features (Mean HR, Triangular Index, LF, HF, LF/HF) and
      nonlinear parameters (SD1, SD2 and SD2/SD1 indices derived from Poincare plots)
      extracted from HRV is analyzed. Statistical analysis was performed using paired
      sample t-test for comparisons of the segments and differences between pre-ictal
      segments were evaluated by Tukey tests. RESULTS: There was slight tachycardia in
      segments near the seizure (30 minutes before: 85.3517 bpm, 5 minutes before:
      119.3630.82 bpm, p=0.0207) which significantly differ from baseline in segments
      far from seizure (240 minutes before: 66.5211.7 bpm). Also there was significant
      increase in LF/HF ratio (30 minutes before: 1.10.22, 5 minutes before: 2.120.5,
      p=0.0332) and SD2/SD1 ratio (30 minutes before: 1.20.15, 5 minutes before:
      2.030.55, p=0.0431) when compared to segments far from the seizure (240 minutes
      before: 0.780.24 and 0.780.14) respectively. Although there was about decrease of
      triangular index in segments near the seizure the percentage of decrease was not
      comparable to segments far from the seizure. CONCLUSION: Significant changes of
      HRV parameters in pre-ictal (5 minutes before the seizure) are obviously higher
      in comparison to interictal baseline. Pre-ictal significant changes of HRV
      suggesting that this time can be considered as prediction time for designing an
      algorithm of early detection of seizure onset based on HRV.

PMID- 24108759
TI  - Almanac 2013: acute coronary syndromes.
AB  - Unstable coronary artery plaque is the most common underlying cause of acute
      coronary syndromes (ACS) and can manifest as unstable angina, non-ST segment
      elevation infarction (NSTE-ACS), and ST elevation myocardial infarction (STEMI),
      but can also manifest as sudden cardiac arrest due to ischaemia induced
      tachyarrhythmias. ACS mortality has decreased significantly over the last few
      years, especially from the more extreme manifestations of ACS, STEMI, and cardiac
      arrest. This trend is likely to continue based on recent therapeutic progress
      which includes novel antiplatelet agents such as prasugrel, ticagrelor, and
      cangrelor. 

PMID- 24108760
TI  - Long-term prognosis of mild functional tricuspid regurgitation after mitral valve
      replacement.
AB  - OBJECTIVE: Functional tricuspid regurgitation (FTR) is the most common type of
      tricuspid insufficiency and occurs approximately in 30% of patients with mitral
      valve disease. The major etiologic factor in the triggering of right ventricular
      dilation and thus causing functional tricuspid regurgitation, is pulmonary artery
      hypertension secondary to mitral valve disease. We aimed to analyze long-term
      outcomes of patients with mild tricuspid regurgitation at the time of mitral
      valve replacement. METHODS: Sixty-six patients with mild tricuspid insufficiency
      who underwent mitral valve replacement were included in this observational
      retrospective study. Mean follow-up time was 8.3 +/- 0.7 years. Patients whose
      tricuspid regurgitation remained unchanged or decreased following operation were
      enrolled to group 1 (n=32), patients whose tricuspid regurgitation increased were
      included to group 2 (n=34) and data were compared statistically with t-test, Mann
      Whitney U, Chi-square and Fisher Exact test. Multiple regression analysis was
      performed to determine independent risk factors for FTR progression.
      REESULTS:Preoperatively female gender (p=0.02), body surface area (p=0.04), left
      atrium diameter (p=0.01), functional capacity (p=0.03), right ventricle diameter
      (p=0.04), and left ventricle mass index (p=0.04) were found to be statistically
      significant between groups. In the follow-up; functional capacity, grade of
      tricuspid insufficiency, pulmonary artery pressure, vena contracta width
      (p<0.001), TAPSE (tricuspid annular plane systolic excursion index) (p=0.04),
      annulus diameter (p=0.02), right ventricle diameter (p=0.01), left ventricle mass
      index (p=0.05), and ejection fraction (p=0.02) were found to be statistically
      different between groups. In multiple logistic regression analysis; preoperative
      LA diameter (OR=5.05; 95% CI:1.49-17.12; p=0.009) and female gender (OR=10.93;
      95% CI:1.77-67.31; p=0.01) were found as independent risk factors for FTR
      progression. CONCLUSION: This study revealed that mild FTR might advance to
      moderate to severe grade in more than half of the patients in the follow-up.
      Thus, surgical approach to even mild FTR should be individualized based on
      patient's risk assessment.

PMID- 24108761
TI  - Manipulation of autophagy by HCMV infection is involved in mTOR and influences
      the replication of virus.

PMID- 24108762
TI  - miR-106a confers cisplatin resistance by regulating PTEN/Akt pathway in gastric
      cancer cells.
AB  - Recent studies have shown that microRNA-106a (miR-106a) is overexpressed in
      gastric cancer and contributes to tumor growth. In this study, we investigated
      whether miR-106a mediated resistance of the gastric cancer cell line SGC7901 to
      the chemotherapeutic agent cisplatin (DDP). MiR-106a expression was up-regulated
      in the DDP resistant cell line SGC7901/DDP compared with its parental line
      SGC7901. Transfection of miR-106a induced DDP resistance in SGC7901, while
      suppression of miR-106a in SGC7901/DDP led to enhanced DDP cytotoxicity. Further
      study indicated that the mechanism of miR-106a-induced DDP resistance involved
      the expression of phosphatase and tensin homolog deleted from chromosome 10
      (PTEN) protein and its downstream phosphatidylinositol 3 kinase (PI3K)/protein
      kinase B (AKT) pathway. This study provides a novel mechanism of DDP resistance
      in gastric cancer. 

PMID- 24108763
TI  - Identification of a miRNA signature in neutrophils after traumatic injury.
AB  - Traumatic injury is the cause of significant mortality and morbidity. The
      molecular mechanisms underlying traumatic injury logically involve changes in
      gene expression that may be regulated through microRNAs (miRNAs). However, the
      association between miRNA deregulation and traumatic injury is largely unknown.
      The purpose of the present study is to address this issue. In this study, we used
      microarray profiling to evaluate the differential expressions of miRNAs in
      neutrophils obtained from patients with major trauma (injury severity scores
      >16), relative to healthy individuals. This neutrophilic miRNA signature was
      further validated using quantitative real-time reverse transcription-polymerase
      chain reaction (qRT-PCR). Genes and signaling pathways related to trauma-induced
      deregulated miRNAs were investigated in silico using the ontology-based and
      network mapping algorithms of Gene Ontology and Kyoto Encyclopedia of Genes or
      Genomes. Results showed that 13 miRNAs in neutrophils of major trauma patients
      were significantly and differentially expressed compared with the miRNA profiles
      of healthy controls. The results of qRT-PCR and in silico analysis revealed that
      miR-23a-5p, miR-30e-3p, miR-223-5p, miR-3945, miR-155-5p, and miR-150-5p were
      likely participants in the traumatic pathogenesis of these patients. In
      conclusion, neutrophils associated with traumatic injury were found to have a
      unique miRNA signature. Changes in signaling pathways due to deregulated miRNAs
      may be involved in the pathological processes of traumatic injury. 

PMID- 24108764
TI  - Enoyl coenzyme a hydratase domain-containing 2, a potential novel regulator of
      myocardial ischemia injury.
AB  - BACKGROUND: We reported previously that Brown Norway (BN) rats are more resistant
      to myocardial ischemia/reperfusion (I/R) injury than are Dahl S (SS) rats. To
      identify the unique genes differentially expressed in the hearts of these rats,
      we used DNA microarray analysis and observed that enoyl coenzyme A hydratase
      containing domain 2 (ECHDC2) is highly expressed (~18-fold) in the SS hearts
      compared with the BN hearts. METHODS AND RESULTS: RT-PCR, Western blot, and
      immunohistochemistry analyses verified that ECHDC2 was highly expressed in SS
      hearts compared with the BN hearts. ECHDC2 gene locates at chromosome 5 of rat
      and is expressed in mitochondria of the heart, mainly in cardiomyocytes but not
      in cardiofibroblasts. Overexpression of ECHDC2 in cells increased susceptibility
      to I/R injury while knockdown of ECHDC2 enhanced resistance to I/R injury.
      Furthermore, we observed that left anterior descending coronary artery ligation
      induced myocardial infarction was more severe in the SS hearts than in the BN
      hearts or SSBN5 hearts, which was built on SS rats but had the substitution of
      chromosome 5 from BN rats. We also demonstrated that ECHDC2 did not alter
      mitochondrial O2 consumption, metabolic intermediates and ATP production. By gas
      chromatography-mass spectrometry, we found that ECHDC2 overexpression increased
      the levels of the cellular branched chain amino acids leucine and valine.
      CONCLUSION: ECHDC2, a mitochondrial protein, may be involved in regulating cell
      death and myocardial injury. Its deficiency in BN rats contributes to their
      increased resistance to myocardial I/R compared with SS rats. ECHDC2 increases
      branched chain amino acid metabolism and appears to be a novel regulator linking
      cell metabolism with cardiovascular disease.

PMID- 24108765
TI  - Infected total knee arthroplasty due to postoperative wound contamination with
      Pasteurella multocida.
AB  - Pasteurella multocida is a small Gram-negative bacterium comprising part of the
      normal gastrointestinal and nasopharyngeal flora of domestic pets, such as dogs
      and cats. It rarely causes infection in humans. Previous reports of P multocida
      causing prosthetic joint infection have described either haematogenous spread of
      infection from a distant site through a scratch or bite, or reactivation of
      infection from a previous injury. We report a case of acute total knee
      arthroplasty joint infection becoming acutely infected by P multocida. We
      postulate that the mechanism of infection was direct contamination of the wound
      as a consequence of the patient being licked by his pet dog. We discuss the
      potential role played by thromboprophylaxis as a factor contributing to prolonged
      wound leak. 

PMID- 24108766
TI  - Clostridium perfringens gas gangrene at a wrist intravenous line insertion.
AB  - A patient admitted to the intensive care unit for management of hypotension
      following a multiple medications overdose subsequently deteriorated rapidly with
      sepsis. A cannula site was noted to be bruised, swollen and erythematous and the
      X-ray demonstrated gas sitting within the tissues surrounding the metacarpal
      bones. The patient was referred to the orthopaedic surgeons and quickly taken for
      debridement of the affected area and fasciotomies of the forearm. Microbiological
      investigation confirmed Clostridium perfringens to be present in multiple fluid
      samples taken from the affected site. 

PMID- 24108767
TI  - V1-V2-V3-V4 T wave inversion: left or right ventricle?
AB  - An 84-year-old woman, affected by Alzheimer's disease, presented to the emergency
      department with intense dyspnoea. Since ECG was showing T wave inversion in
      anterior leads and troponin-T was high, the patient was admitted to our unit with
      a diagnosis of anterior non-ST elevation myocardial infarction. However, the
      patient's medical history and a further review of the ECG led us to suspect a
      pulmonary embolism (PE) as a possible differential clinical diagnosis. We tested
      this alternative hypothesis: echocardiography as well as contrast-enhanced CT
      scan confirmed the diagnosis of PE. We describe these misleading ECG findings
      together with a brief discussion of electrocardiographical changes in pulmonary
      embolism. 

PMID- 24108768
TI  - The first report of survival post Rothia aeria endocarditis.
AB  - A 61-year-old patient presented with drowsiness, decreased appetite and weight
      loss. On examination he had several splinter haemorrhages and a tender mass over
      the right temporal region. Respiratory and abdominal examinations were
      unremarkable and heart sounds were normal with no clinically audible murmurs. He
      spiked regular temperatures and consequently had several blood cultures taken.
      Transthoracic and transoeseophageal echocardiogram showed a 3 cm mitral valve
      vegetation. MRI confirmed suspicions of septic emboli in the brain. Blood
      cultures grew Rothia aeria and he was started on benzylpenicillin, rifampicin and
      gentamicin. After a period of observation he deteriorated clinically and
      biochemically, surgical intervention therefore ensued with an urgent metallic
      mitral valve replacement. Nineteen days postsurgery the patient was successfully
      discharged on outpatient antibiotic therapy and warfarin. In view of
      complications such as embolisation and cerebral infarction, R aeria endocarditis
      should be managed aggressively and with a high index of clinical suspicion. 

PMID- 24108769
TI  - Primary pulmonary melanoma: the unexpected tumour.
AB  - A 62-year-old woman was referred to our pulmonology team with exertional dyspnoea
      and chest tightness of 2 months duration. Her medical history included cervical
      cancer and thyroid nodules. Imaging studies showed collapse of left upper lobe.
      Fiberoptic bronchoscopy unveiled an endoluminal lesion and bronchial biopsy
      displayed features of melanoma. She denied a history of melanoma or excision of
      lesions of skin, mucous membranes or the eye. A thorough evaluation including
      combined positron emission tomography with CT scan excluded other possible sites
      of primary melanoma, but there was a metastasis in a thoracic vertebra.
      Palliative radiotherapy of the spine was performed. Chemotherapy initiation with
      dacarbazine was postponed by the appearance of a malignant pleural effusion,
      confirmed by pleural fluid cytology. After four cycles chemotherapy was
      discontinued due to disease progression. The patient is still alive with a follow
      up of 12 months, currently on best supportive care. 

PMID- 24108770
TI  - Floating thrombus in the left upper pulmonary vein dissolved by dabigatran.
AB  - Pulmonary vein thrombosis (PVT) is a rare but life-threatening condition.
      Although warfarin reduces the risk of atrial fibrillation (AF)-related stroke by
      64%, the use of this drug has some limitations. Dabigatran is a relatively novel
      therapeutic option for patients with AF. The mechanism of action of dabigatran is
      unclear, and its ability to dissolve pulmonary vein thrombi is uncertain. Scans
      from a 64-slice multidetector CT (64-MDCT) scanner can evaluate coronary artery
      stenosis and detect left atrial appendage thrombi and pulmonary vein thrombi. A
      73-year-old male patient presented with chest pain, and a 64-MDCT scan was
      performed to assess coronary artery stenosis. The 64-MDCT scan showed no stenosis
      but it did reveal a thrombus located in the centre of the left upper pulmonary
      vein. After 3 months of dabigatran therapy, the thrombus disappeared. This is the
      first case report of dabigatran dissolving a left upper pulmonary vein thrombus,
      as assessed by a 64-MDCT scan. 

PMID- 24108771
TI  - An unfamiliar presentation of a lateral periodontal cyst.
AB  - Lateral periodontal cyst, developmental in origin, typically is observed in the
      cuspid-bicuspid region of the mandible and less frequently in the maxilla. It may
      arise initially as a dentigerous cyst developing by expansion of the follicle
      along the lateral surface of the crown which eventually comes to lie on the
      lateral aspect of the root if tooth eruption is normal. Alternatively, it may
      arise from the cell rests of malassez. The incidence of lateral periodontal cysts
      has been reported to be less than 1% and these cysts represent nearly 0.8% of all
      central cysts of the maxillary bone. Here we present one such case with unusual
      findings. 

PMID- 24108772
TI  - Osler-Weber-Rendu syndrome.

PMID- 24108773
TI  - Osteomalacia as inaugural manifestation of Sjogren syndrome.
AB  - Osteomalacia is a relatively common condition, which is frequently underdiagnosed
      due to lack of clinical suspicion and non-specific symptoms. Osteomalacia can
      complicate tubulo-interstital nephritis. However, it occurs exceptionally as the
      first manifestation of Sjogren syndrome with renal involvement. It is a
      consequence of chronic metabolic acidosis and is associated with distal renal
      tubular acidosis. We report a 31-year-old woman hospitalised for a 1 year history
      of muscle weakness and joint and chest wall pains. Skeletal imagery showed
      Looser's zones in the left femoral neck. Investigations concluded to the
      diagnosis of primary Sjogren's syndrome. 

PMID- 24108774
TI  - Risky behaviour: a rare complication of an uncommon disease in a returning
      traveller.
AB  - A 49-year-old man with a history of hypertension and no known drug allergies was
      admitted with a 4-day history of fever, general malaise, sore throat and
      diarrhoea. Eleven days ago, he had returned from a 2-week adventure holiday to
      South Africa. On admission, he was noted to have a creatinine 392 umol/L, alanine
      aminotransferase 133 IU/L, alkaline phosphatase 211 IU/L and platelets
      151*10(9)/L. A differential diagnosis of suspected leptospirosis or bacterial
      sepsis was made and he was started on ceftriaxone. Two hours later he became
      hypotensive, tachypnoeic with severe myalgia and a temperature of 41 degrees C,
      type I respiratory failure and metabolic acidosis. There was no stridor, facial
      swelling or rash. A diagnosis of Jarisch-Herxheimer reaction was made. A second
      dose of ceftriaxone was given without any reaction. The patient thereafter
      completed 7 days of doxycycline. PCR confirmed leptospirosis and subsequent
      leptospirosis IgM was positive. He improved clinically with treatment and was
      discharged after 10 days of admission. 

PMID- 24108776
TI  - Stroke mimicking acute myocardial infarction.

PMID- 24108775
TI  - Brown-McLean syndrome.
AB  - An 80-year-old Chinese man with high myopia and a history of right eye cataract
      extraction and superior peripheral iridectomy developed peripheral corneal oedema
      after a period of aphakia. The peripheral corneal oedema was static over years
      and did not progress to involve central cornea hence his visual acuity remained
      stable. The condition was compatible with the relatively rare Brown-McLean
      syndrome. Specular microscopy showed normal endothelial cell density in the
      oedematous peripheral as well as central cornea. While anterior segment optical
      coherence tomography demonstrated the cross-sectional architecture of cornea,
      Scheimpflug imaging was used to measure the peripheral corneal thickening and to
      demonstrate increased corneal density as compared with the contralateral normal
      eye. These investigations not only help better characterise the rare disease, but
      also in precisely monitoring any disease progression by periodic measurements. 

PMID- 24108777
TI  - Pyoderma gangrenosum of the abdominal wall.

PMID- 24108778
TI  - Evaluation of a prototype flow cytometry test for serodiagnosis of canine
      visceral leishmaniasis.
AB  - Diagnosing canine visceral leishmaniasis (CVL) is a critical challenge since
      conventional immunoserological tests still present some deficiencies. The current
      study evaluated a prototype flow cytometry serology test, using antigens and
      fluorescent antibodies that had been stored for 1 year at 4 degrees C, on a broad
      range of serum samples. Noninfected control dogs and Leishmania infantum-infected
      dogs were tested, and the prototype test showed excellent performance in
      differentiating these groups with high sensitivity, specificity, positive and
      negative predictive values, and accuracy (100% in all analyses). When the CVL
      group was evaluated according to the dogs' clinical status, the prototype test
      showed outstanding accuracy in all groups with positive serology (asymptomatic
      II, oligosymptomatic, and symptomatic). However, in dogs which had positive
      results by PCR-restriction fragment length polymorphism (RFLP) but negative
      results by conventional serology (asymptomatic I), serological reactivity was not
      observed. Additionally, sera from 40 dogs immunized with different vaccines
      (Leishmune, Leish-Tec, or LBSap) did not present serological reactivity in the
      prototype test. Eighty-eight dogs infected with other pathogens (Trypanosoma
      cruzi, Leishmania braziliensis, Ehrlichia canis, and Babesia canis) were used to
      determine cross-reactivity and specificity, and the prototype test performed
      well, particularly in dogs infected with B. canis and E. canis (100% and 93.3%
      specificities, respectively). In conclusion, our data reinforce the potential of
      the prototype test for use as a commercial kit and highlight its outstanding
      performance even after storage for 1 year at 4 degrees C. Moreover, the prototype
      test efficiently provided accurate CVL serodiagnosis with an absence of false
      positive results in vaccinated dogs and minor cross-reactivity against other
      canine pathogens.

PMID- 24108779
TI  - Immunogenicity and safety after booster vaccination of diphtheria, tetanus, and
      acellular pertussis in young adults: an open randomized controlled trial in
      Japan.
AB  - The recent increase of pertussis in young adults in Japan is hypothesized to be
      due in part to waning protection from the acellular pertussis vaccine. While a
      booster immunization may prevent an epidemic of pertussis among these young
      adults, little is known about the safety and immunogenicity of such a booster
      with the diphtheria, tetanus, and acellular pertussis vaccine (DTaP), which is
      currently available in Japan. One hundred and eleven medical students with a mean
      age of 19.4 years were randomly divided into 2 groups of 55 and 56 subjects and
      received, respectively, 0.2 or 0.5 ml of DTaP. Immunogenicity was assessed by
      performing the immunoassay using serum, and the geometric mean concentration
      (GMC), GMC ratio (GMCR), seropositive rate, and booster response rate were
      calculated. Adverse reactions and adverse events were monitored for 7 days after
      vaccination. After booster vaccination in the two groups, significant increases
      were found in the antibodies against pertussis toxin, filamentous hemagglutinin,
      diphtheria toxoid, and tetanus toxoid, and the booster response rates for all
      subjects reached 100%. The GMCs and GMCRs against all antigens were significantly
      higher in the 0.5-ml group than in the 0.2-ml group. No serious adverse events
      were observed. Frequencies of local reactions were similar in the 2 groups,
      although the frequency of severe local swelling was significantly higher in the
      0.5-ml group. These data support the acceptability of booster immunization using
      both 0.2 and 0.5 ml of DTaP for young adults for controlling pertussis. (This
      study was registered at UMIN-CTR under registration number UMIN000010672.).

PMID- 24108780
TI  - Immunogenicity, safety, and lot consistency of a novel inactivated enterovirus 71
      vaccine in Chinese children aged 6 to 59 months.
AB  - The determination of lot-to-lot consistency in the manufacturing process is a
      mandatory step in the clinical development of the novel enterovirus 71 (EV71)
      vaccine. A phase III, randomized, placebo-controlled, double-blind trial assessed
      the lot consistency, immunogenicity, and safety of the EV71 vaccine in children
      aged 6 to 59 months. Healthy children (n = 1,400) received one of three lots of
      the EV71 vaccine containing 400 U of EV71 antigen or a placebo at days 0 and 28.
      Blood samples were collected before dose 1 and at 28 days after dose 2 (day 56)
      for an anti-EV71 neutralizing antibody (NTAb) assay. The geometric mean titer
      (GMT) and the seropositivity rates (with titers of >=1:8) were compared at day
      56. After each dose, the solicited injection site and general adverse events
      (AEs) were recorded for 7 days, and unsolicited AEs were recorded for 28 days. At
      day 56, the seropositivity rates ranged from 99.7% to 100% for the vaccine
      groups. The NTAb GMTs for the vaccine were 140.3 (95% confidence interval [CI],
      117.8 to 167.1), 141.5 (95% CI, 118.0 to 169.6), and 146.6 (95% CI, 122.5 to
      175.3). The two-sided 95% CI of the log difference in GMTs between the pairs of
      lots were between -0.176 and 0.176, therefore meeting the predefined equivalence
      criteria. The percentages of subjects reporting any injection site AEs, general
      AEs, or serious AEs were similar across the four vaccination groups. In
      conclusion, the demonstration of consistency between the manufacturing lots
      confirms for the purposes of clinical development the reliability of the EV71
      vaccine production process. (This study has been registered at ClinicalTrials.gov
      under registration no. NCT01636245.).

PMID- 24108781
TI  - Dietary patterns and breast cancer risk in the California Teachers Study cohort.
AB  - BACKGROUND: Evidence that diet is associated with breast cancer risk is
      inconsistent. Most studies have examined risks associated with specific foods and
      nutrients, rather than measures of overall diet. OBJECTIVE: This study aimed to
      evaluate dietary patterns and their relation to breast cancer risk in a large
      cohort of women. DESIGN: Data from 91,779 women in the California Teachers Study
      cohort were analyzed, including data from 4140 women with a diagnosis of invasive
      breast cancer made between 1995 and 2009. Five predominant dietary patterns were
      identified by using principal components factor analysis: a plant-based diet,
      high in fruit and vegetables; a high-protein, high-fat diet, high in meats, eggs,
      fried foods, and high-fat condiments; a high-carbohydrate diet, high in
      convenience foods, pasta, and bread products; an ethnic diet, high in legumes,
      soy-based foods, rice, and dark-green leafy vegetables; and a salad and wine
      diet, high in lettuce, fish, wine, low-fat salad dressing, and coffee and tea.
      RESULTS: The plant-based pattern was associated with a reduction in breast cancer
      risk (RR: 0.85; 95% CI: 0.76, 0.95 for the highest compared with the lowest
      consumption quintile; P-trend = 0.003); risk reduction was greater for estrogen
      receptor-negative progesterone receptor-negative (ER-PR-) tumors (RR: 0.66; 95%
      CI: 0.48, 0.91; P-trend = 0.03). The salad and wine pattern was associated with
      an increased risk of estrogen receptor-positive progesterone receptor-positive
      tumors (RR: 1.29; 95% CI: 1.12, 1.49); this effect was only slightly attenuated
      after adjustment for alcohol consumption. CONCLUSION: The finding that greater
      consumption of a plant-based dietary pattern is associated with a reduced breast
      cancer risk, particularly for ER-PR- tumors, offers a potential avenue for
      prevention.

PMID- 24108783
TI  - Effect of vitamin D supplementation on antibiotic use: a randomized controlled
      trial.
AB  - BACKGROUND: Observational data suggested that supplementation with vitamin D
      could reduce risk of infection, but trial data are inconsistent. OBJECTIVE: We
      aimed to examine the effect of oral vitamin D supplementation on antibiotic use.
      DESIGN: We conducted a post hoc analysis of data from pilot D-Health, which is a
      randomized trial carried out in a general community setting between October 2010
      and February 2012. A total of 644 Australian residents aged 60-84 y were randomly
      assigned to receive monthly doses of a placebo (n = 214) or 30,000 (n = 215) or
      60,000 (n = 215) IU oral cholecalciferol for <=12 mo. Antibiotics prescribed
      during the intervention period were ascertained by linkage with pharmacy records
      through the national health insurance scheme (Medicare Australia). RESULTS:
      People who were randomly assigned 60,000 IU cholecalciferol had nonsignificant
      28% lower risk of having antibiotics prescribed at least once than did people in
      the placebo group (RR: 0.72; 95% CI: 0.48, 1.07). In analyses stratified by age,
      in subjects aged >=70 y, there was a significant reduction in antibiotic use in
      the high-dose vitamin D compared with placebo groups (RR: 0.53; 95% CI: 0.32,
      0.90), whereas there was no effect in participants aged <70 y (RR: 1.07; 95% CI:
      0.58, 1.97) (P-interaction = 0.1). CONCLUSION: Although this study was a post hoc
      analysis and statistically nonsignificant, this trial lends some support to the
      hypothesis that supplementation with 60,000 IU vitamin D/mo is associated with
      lower risk of infection, particularly in older adults. The trial was registered
      at the Australian New Zealand Clinical Trials Registry (anzctr.org.au) as
      ACTRN12609001063202.

PMID- 24108782
TI  - The association between MTHFR 677C>T genotype and folate status and genomic and
      gene-specific DNA methylation in the colon of individuals without colorectal
      neoplasia.
AB  - BACKGROUND: Decreased genomic and increased gene-specific DNA methylation
      predispose to colorectal cancer. Dietary folate intake and the
      methylenetetrahydrofolate reductase polymorphism (MTHFR 677C>T) may influence
      risk by modifying DNA methylation. OBJECTIVE: We investigated the associations
      between MTHFR 677C>T genotype, folate status, and DNA methylation in the colon.
      DESIGN: We conducted a cross-sectional study of 336 men and women (age 19-92 y)
      in the United Kingdom without colorectal neoplasia. We obtained blood samples for
      measurement of serum and red blood cell folate, plasma homocysteine, and MTHFR
      677C>T genotype and colonic tissue biopsies for measurement of colonic tissue
      folate and DNA methylation (genomic- and gene-specific, estrogen receptor 1,
      ESR1; myoblast determination protein 1, MYOD1; insulin-like growth factor II,
      IGF2; tumor suppressor candidate 33, N33; adenomatous polyposis coli, APC; mut-L
      homolog 1, MLH1; and O(6)-methylguanine-DNA methyltransferase, MGMT) by liquid
      chromatography/electrospray ionization mass spectrometry and pyrosequencing,
      respectively. RESULTS: Of the 336 subjects recruited, 185 (55%) carried the CC,
      119 (35%) the CT, and 32 (10%) the TT alleles. No significant differences in
      systemic markers of folate status and colonic tissue folate between genotypes
      were found. The MTHFR TT genotype was not associated with genomic or gene
      specific DNA methylation. Biomarkers of folate status were not associated with
      genomic DNA methylation. Relations between biomarkers of folate status and gene
      specific methylation were inconsistent. However, low serum folate was associated
      with high MGMT methylation (P = 0.001). CONCLUSION: MTHFR 677C>T genotype and
      folate status were generally not associated with DNA methylation in the colon of
      a folate-replete population without neoplasia.

PMID- 24108784
TI  - Autophagic-lysosomal pathway is the main proteolytic system modified in the
      skeletal muscle of esophageal cancer patients.
AB  - BACKGROUND: In cancer cachexia, muscle depletion is related to morbidity and
      mortality. Muscle-wasting mechanisms in cancer patients are not fully understood.
      OBJECTIVE: We investigated the involvement of the proteolytic systems
      (proteasome, autophagic-lysosomal, calpain, and caspase) in muscle wasting during
      cancer cachexia. DESIGN: Esophageal cancer patients [n = 14; mean +/- SD age:
      64.1 +/- 6.6 y] and weight-stable control patients undergoing reflux surgery (n =
      8; age: 57.5 +/- 5.8 y) were included. Enzymatic activities were measured in the
      vastus lateralis and diaphragm. Protein expressions were also measured in the
      vastus lateralis of control (n = 7) and cancer (n = 8) patients. RESULTS:
      Proteasome, calpain, and caspase 3 activities in the vastus lateralis and
      diaphragm muscles did not differ between the 2 groups. Cathepsin B and L
      activities were 90% (+/- SD) [2.4 +/- 0.2 compared with 1.3 +/- 0.2 pmol 7-amido
      4-methylcoumarin (AMC) . MUg protein-1 . min-1; P < 0.001] and 115% (5.3 +/- 0.4
      compared with 2.5 +/- 0.3 pmol AMC . MUg protein-1 . min-1; P < 0.001) greater,
      respectively, in the vastus lateralis of cancer patients than in that of control
      subjects. We observed (in conjunction with increased lysosomal protease
      activities) higher microtubule-associated protein 1 light chain 3B-II/I ratios
      (0.14 +/- 0.08 compared with 0.04 +/- 0.04) and cathepsin B and L expressions in
      the vastus lateralis of cancer patients than in that of control subjects (P <
      0.05). Protein expression of p62 in the vastus lateralis did not differ between
      the 2 groups. CONCLUSIONS: The autophagic-lysosomal pathway in the skeletal
      muscle of cancer patients was modified, whereas other proteolytic systems were
      unchanged. These findings suggest involvement of the autophagic-lysosomal
      proteolytic system during cancer cachexia development in humans.

PMID- 24108785
TI  - High folate and low vitamin B-12 intakes during pregnancy are associated with
      small-for-gestational age infants in South Indian women: a prospective
      observational cohort study.
AB  - BACKGROUND: Folic acid supplementation in those with a low vitamin B-12 intake or
      status may have adverse effects. These effects are unknown with regard to birth
      outcome in pregnant Indian women who are routinely supplemented with high doses
      of folic acid. OBJECTIVE: The objective was to examine the association of
      unbalanced vitamin B-12 and total folate (folic acid supplement + dietary folate)
      intakes during pregnancy with outcomes in small-for-gestational-age (SGA)
      infants. DESIGN: This was a prospective observational cohort study of 1838
      pregnant women in South India. Low intake of dietary vitamin B-12 in the presence
      of high total folate intake was examined as the ratio of vitamin B-12 intake to
      total folate intake. RESULTS: The inadequacy of vitamin B-12 intake (<1.2 MUg/d)
      assessed by a food-frequency questionnaire in the first, second, and third
      trimesters of pregnancy was 25%, 11%, and 10%, respectively. Multivariate log
      binomial regression showed that low vitamin B-12 and folate intakes in the first
      trimester were independently associated with a higher risk of SGA. In a subgroup
      of women with high supplemental folic acid intakes in the second trimester, those
      with the lowest tertile of vitamin B-12:folate ratio had a higher risk of SGA
      outcome than did those in the highest tertile (adjusted RR: 2.73; 95% CI: 1.17,
      6.37). A similar trend was observed in the analysis of blood micronutrient status
      in a random subset (n = 316) of the sample. CONCLUSIONS: These findings suggest
      that, in addition to vitamin B-12 and folate deficiencies alone, there may be
      adverse birth outcomes associated with unbalanced vitamin B-12 and folate intakes
      or status during pregnancy. These findings have important implications for the
      antenatal B vitamin supplementation policy in India. This trial was registered at
      the Clinical Trial Registry of India as 2013/07/005342.

PMID- 24108786
TI  - Postnatal dietary fatty acid composition permanently affects the structure of
      hypothalamic pathways controlling energy balance in mice.
AB  - BACKGROUND: We previously reported that dietary lipid quality during early life
      can have long-lasting effects on metabolic health and adiposity. Exposure to a
      postnatal diet with low dietary omega-6 (n-6) or high omega-3 (n-3) fatty acid
      (FA) content resulted in reduced body fat accumulation when challenged with a
      moderate Western-style diet (WSD) beginning in adolescence. OBJECTIVE: We
      determined whether this programming effect is accompanied by changes in
      hypothalamic neural projections or modifications in the postnatal leptin surge,
      which would indicate the altered development of hypothalamic circuits that
      control energy balance. DESIGN: Neonatal mice were subjected to a control diet
      (CTR) or experimental diet with altered relative n-6 and n-3 FA contents [ie, a
      diet with a relative reduction in n-6 fatty acid (LOW n-6) or a diet with a
      relative increase in n-3 fatty acid (HIGH n-3) compared with the CTR from
      postnatal day (PN) 2 to 42]. RESULTS: Compared with CTR mice, mice fed a LOW n-6
      or HIGH n-3 during postnatal life showed significant reductions in the density of
      both orexigenic and anorexigenic neural projections to the paraventricular
      nucleus of the hypothalamus at PN 28. These impairments persisted into adulthood
      and were still apparent after the WSD challenge between PNs 42 and 98. However,
      the neuroanatomical changes were not associated with changes in the postnatal
      leptin surge. CONCLUSION: Although the exact mechanism remains to be elucidated,
      our data indicate that the quality of dietary FA during postnatal life affects
      the development of the central regulatory circuits that control energy balance
      and may do so through a leptin-independent mechanism.

PMID- 24108788
TI  - Transmission electron microscopy study of microstructural properties and
      dislocation characterization in the GaN film grown on the cone-shaped patterned
      Al2O3 substrate.
AB  - Growing a GaN film on a patterned Al2O3 substrate is one of the methods of
      reducing threading dislocations (TDs), which can significantly deteriorate the
      performance of GaN-based LEDs. In this study, the microstructural details of the
      GaN film grown on a cone-shaped patterned Al2O3 substrate were investigated using
      high-resolution transmission electron microscopy and weak-beam dark-field
      techniques. Various defects such as misfit dislocations (MDs), recrystallized GaN
      (R-GaN) islands and nano-voids were observed on the patterned Al2O3 surfaces,
      i.e. the flat surface (FS), the inclined surface (IS) and the top surface (TS),
      respectively. Especially, the crystallographic orientation of R-GaN between the
      GaN film and the inclined Al2O3 substrate was identified as $[?overline 1
      2?overline 1 0]_{{?rm GaN}} ?hbox{//}[?overline 1 101]_{{?rm R - GaN} ?,{?rm
      on}?,{?rm IS}} ?hbox{//}[?overline 1 100]_{ {{?rm Al}} _{?rm 2} {?rm O}_{?rm 3}}
      $, $(?overline 1 012)_{{?rm GaN}} ?hbox{//}(1?overline 1 02)_{{?rm R - Ga}?,{?rm
      Non}?,{?rm IS}} ?hbox{//}(?overline {11} 26)_{ {{?rm Al}} _{?rm 2} {?rm O}_{?rm
      3}} $. In addition, a rotation by 9 degrees  between $(10?overline 1 1)_{{?rm R -
      GaN}} $ and $(0002)_{{?rm GaN}} $ and between $(10?overline 1 1)_{{?rm R - GaN}}
      $ and $(0006)_{ {{?rm Al}} _{?rm 2} {?rm O}_{?rm 3}} $ was found to reduce the
      lattice mismatch between the GaN film and the Al2O3 substrate. Many TDs in the
      GaN film were observed on the FS and TS of Al2O3. However, few TDs were observed
      on the IS. Most of the TDs generated from the FS of Al2O3 were bent to the
      inclined facet rather than propagating to the GaN surface, resulting in a
      reduction in the dislocation density. Most of the TDs generated from the TS of
      Al2O3 were characterized as edge dislocations. 

PMID- 24108789
TI  - Circulating soluble CD27 and CD30 in workers exposed to 2,3,7,8
      Tetrachlorodibenzo-p-dioxin (TCDD).
AB  - Previous studies suggest that 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) exposure
      may be associated with non-Hodgkin lymphoma (NHL) but findings remain
      inconclusive. There is a need for mechanistic studies to evaluate the biologic
      plausibility of this association. In this cross-sectional study, we investigated
      changes in plasma levels of interleukin 1 receptor antagonist (IL1RA) and soluble
      (s)CD27 and sCD30 which have been found to be predictive of lymphoma, among
      workers of a cohort occupationally exposed to TCDD. Eighty-five workers who had
      been exposed to TCDD more than 30 years before blood collection were included in
      the current investigation. Plasma level of the markers was measured by ELISA.
      Current plasma levels of TCDD were determined by high-resolution gas
      chromatography/isotope dilution high-resolution mass spectrometry. TCDD blood
      levels at time of last exposure were estimated using a one-compartment first
      order kinetic model. Exposure-response analyses showed no significant association
      between blood levels of sCD27, and sCD30 and current and estimated TCDD levels at
      time of last exposure. IL1RA showed a borderline significant decrease with
      increasing plasma TCDD levels (P = 0.07), which reached formal statistical
      significance when excluding subjects with chronic diseases. In conclusion, no
      clear dose-response relationship was observed between the measured markers and
      TCDD level. However, there was a suggestion that markers in particular IL1RA
      tended to decrease with increasing TCDD levels. This observation is consistent
      with our earlier observation on decreasing cytokine levels, suggesting
      immunosuppression, with increasing exposures. These findings possibly provide new
      insights in the etiology of NHL and the mechanisms through which TCDD can
      increase lymphoma risk.

PMID- 24108791
TI  - Parity and kidney cancer risk: evidence from epidemiologic studies.
AB  - BACKGROUND: Observational studies have reported conflicting results between
      parity and kidney cancer risk. To our knowledge, a comprehensive and quantitative
      assessment of the association between parity and kidney cancer has not been
      reported. Thus, we conducted a systematic review and dose-response meta-analysis
      of published epidemiologic studies to summarize the evidence of this association.
      METHODS: Relevant published studies of parity and kidney cancer were identified
      using MEDLINE (PubMed) database through end of June 2013. Two authors
      independently assessed eligibility and extracted data. Six prospective and eight
      case-control studies reported relative risk (RR) estimates and 95% confidence
      intervals (CI) of kidney cancer associated with parity or parity number. Fixed-
      or random-effects models were used to estimate summary relative risk. RESULTS:
      The summary relative risk of kidney cancer for the parity versus nulliparous was
      1.23 (95% CI, 1.10-1.36; Q = 12.41; P = 0.413; I(2) = 3.3%). In addition,
      significant association was also found for the highest versus lowest parity
      number, with summary RR = 1.36 (95% CI, 1.19-1.56; Q = 8.24; P = 0.766; I(2) =
      0%). In the dose-response analysis, the summary per one live birth relative risk
      was 1.08 (95% CI: 1.05-1.10; Q = 9.34; P = 0.500; I(2) = 0%), also indicating the
      positive effect of parity on kidney cancer risk. No evidence of publication bias
      and significant heterogeneity between subgroups was detected by meta-regression
      analyses. CONCLUSIONS: In summary, findings from this meta-analysis suggest that
      ever parity and higher parity number is significantly associated with increased
      risk of kidney cancer. IMPACT: The present results suggest a positive association
      between parity and kidney cancer risk.

PMID- 24108790
TI  - An exploratory study of respiratory quotient calibration and association with
      postmenopausal breast cancer.
AB  - BACKGROUND: The respiratory quotient (RQ), defined as the ratio of carbon dioxide
      exhaled to oxygen uptake, reflects substrate utilization when energy is expended.
      Fat and alcohol have RQ values of approximately 0.7, compared with 1.0 for
      carbohydrate, and approximately 0.8 for protein. Here, the association between RQ
      and postmenopausal breast cancer risk is studied. METHODS: Paired RQ measurements
      were obtained, separated by approximately 6 months, for women in the reliability
      subset of a Women's Health Initiative (WHI) Nutrition and Physical Activity
      Assessment Study. Linear regression of the average of the paired log RQ
      assessments on a corresponding log food quotient (FQ) average and other study
      subject characteristics, including age, body mass index, race, and education,
      yielded calibration equations for predicting RQ. RESULTS: Calibration equations,
      using any of food frequency, food record, or dietary recall data, explained an
      appreciable fraction of measured log RQ variation, and these were used to compute
      calibrated RQ estimates throughout WHI cohorts. Calibrated RQ estimates using 4
      day food record (4DFR) data related inversely (P = 0.004) to (invasive) breast
      cancer risk in the WHI Dietary Modification trial comparison group, and
      corresponding RQ estimates using food-frequency data related inversely (P =
      0.002) to breast cancer incidence in this cohort combined with the larger WHI
      observational study. CONCLUSION: Although preliminary, these analyses suggest a
      substantially higher postmenopausal breast cancer risk among women having
      relatively low RQ. IMPACT: RQ elevation could provide a novel target for breast
      cancer risk reduction.

PMID- 24108792
TI  - Central complex neurons exhibit behaviorally gated responses to visual motion in
      Drosophila.
AB  - Sensory systems provide abundant information about the environment surrounding an
      animal, but only a small fraction of that information is relevant for any given
      task. One example of this requirement for context-dependent filtering of a
      sensory stream is the role that optic flow plays in guiding locomotion. Flying
      animals, which do not have access to a direct measure of ground speed, rely on
      optic flow to regulate their forward velocity. This observation suggests that
      progressive optic flow, the pattern of front-to-back motion on the retina created
      by forward motion, should be especially salient to an animal while it is in
      flight, but less important while it is standing still. We recorded the activity
      of cells in the central complex of Drosophila melanogaster during quiescence and
      tethered flight using both calcium imaging and whole cell patch-clamp techniques.
      We observed a genetically identified set of neurons in the fan-shaped body that
      are unresponsive to visual motion while the animal is quiescent. During flight
      their baseline activity increases, and they respond to front-to-back motion with
      changes relative to this baseline. The results provide an example of how nervous
      systems selectively respond to complex sensory stimuli depending on the current
      behavioral state of the animal. 

PMID- 24108793
TI  - Thalamostriatal projections from the medial posterior and parafascicular nuclei
      have distinct topographic and physiologic properties.
AB  - The dorsolateral striatum (DLS) is critical for executing sensorimotor behaviors
      that depend on stimulus-response (S-R) associations. In rats, the DLS receives it
      densest inputs from primary somatosensory (SI) cortex, but it also receives
      substantial input from the thalamus. Much of rat DLS is devoted to processing
      whisker-related information, and thalamic projections to these whisker-responsive
      DLS regions originate from the parafascicular (Pf) and medial posterior (POm)
      nuclei. To determine which thalamic nucleus is better suited for mediating S-R
      associations in the DLS, we compared their input-output connections and neuronal
      responses to repetitive whisker stimulation. Tracing experiments demonstrate that
      POm projects specifically to the DLS, but the Pf innervates both dorsolateral and
      dorsomedial parts of the striatum. The Pf nucleus is innervated by whisker
      sensitive sites in the superior colliculus, and these sites also send dense
      projections to the zona incerta, a thalamic region that sends inhibitory
      projections to the POm. These data suggest that projections from POm to the DLS
      are suppressed by incertal inputs when the superior colliculus is activated by
      unexpected sensory stimuli. Simultaneous recordings with two electrodes indicate
      that POm neurons are more responsive and habituate significantly less than Pf
      neurons during repetitive whisker stimulation. Response latencies are also
      shorter in POm than in Pf, which is consistent with the fact that Pf receives its
      whisker information via synaptic relays in the superior colliculus. These
      findings indicate that, compared with the Pf nucleus, POm transmits somatosensory
      information to the DLS with a higher degree of sensory fidelity. 

PMID- 24108794
TI  - Whole person-evoked fMRI activity patterns in human fusiform gyrus are accurately
      modeled by a linear combination of face- and body-evoked activity patterns.
AB  - Visual cues from the face and the body provide information about another's
      identity, emotional state, and intentions. Previous neuroimaging studies that
      investigated neural responses to (bodiless) faces and (headless) bodies have
      reported overlapping face- and body-selective brain regions in right fusiform
      gyrus (FG). In daily life, however, faces and bodies are typically perceived
      together and are effortlessly integrated into the percept of a whole person,
      raising the possibility that neural responses to whole persons are qualitatively
      different than responses to isolated faces and bodies. The present study used
      fMRI to examine how FG activity in response to a whole person relates to activity
      in response to the same face and body but presented in isolation. Using
      multivoxel pattern analysis, we modeled person-evoked response patterns in right
      FG through a linear combination of face- and body-evoked response patterns. We
      found that these synthetic patterns were able to accurately approximate the
      response patterns to whole persons, with face and body patterns each adding
      unique information to the response patterns evoked by whole person stimuli. These
      results suggest that whole person responses in FG primarily arise from the
      coactivation of independent face- and body-selective neural populations. 

PMID- 24108795
TI  - Effects of the motor cortical quadripulse transcranial magnetic stimulation (QPS)
      on the contralateral motor cortex and interhemispheric interactions.
AB  - Corpus callosum connects the bilateral primary motor cortices (M1s) and plays an
      important role in motor control. Using the paired-pulse transcranial magnetic
      stimulation (TMS) paradigm, we can measure interhemispheric inhibition (IHI) and
      interhemispheric facilitation (IHF) as indexes of the interhemispheric
      interactions in humans. We investigated how quadripulse transcranial magnetic
      stimulation (QPS), one form of repetitive TMS (rTMS), on M1 affects the
      contralateral M1 and the interhemispheric interactions. QPS is able to induce
      bidirectional plastic changes in M1 depending on the interstimulus intervals
      (ISIs) of TMS pulses: long-term potentiation (LTP)-like effect by QPS-5 protocol,
      and long-term depression-like effect by QPS-50, whose numbers indicate the ISI
      (ms). Twelve healthy subjects were enrolled. We applied QPS over the left M1 and
      recorded several parameters before and 30 min after QPS. QPS-5, which increased
      motor-evoked potentials (MEPs) induced by left M1 activation, also increased MEPs
      induced by right M1 activation. Meanwhile, QPS-50, which decreased MEPs elicited
      by left M1 activation, did not induce any significant changes in MEPs elicited by
      right M1 activation. None of the resting motor threshold, active motor threshold,
      short-interval intracortical inhibition, long-interval intracortical inhibition,
      intracortical facilitation, and short-interval intracortical inhibition in right
      M1 were affected by QPS. IHI and IHF from left to right M1 significantly
      increased after left M1 QPS-5. The degree of left first dorsal interosseous MEP
      amplitude change by QPS-5 significantly correlated with the degree of IHF change.
      We suppose that the LTP-like effect on the contralateral M1 may be produced by
      some interhemispheric interactions through the corpus callosum. 

PMID- 24108797
TI  - Spatial constant equi-affine speed and motion perception.
AB  - The two-thirds power law, postulating an inverse local relation between the
      velocity and cubed root of curvature of planar trajectories, is a long
      established simplifying principle of human hand movements. In perception, the
      motion of a dot along a planar elliptical path appears most uniform for speed
      profiles closer to those predicted by the power law than to constant Euclidean
      speed, a kinetic-visual illusion. Mathematically, complying with this law is
      equivalent to moving at constant planar equi-affine speed, while unconstrained
      three-dimensional drawing movements generally follow constant spatial equi-affine
      speed. Here we test the generalization of this illusion to visual perception of
      spatial motion for a dot moving along five differently shaped paths, using
      stereoscopic projection. The movements appeared most uniform for speed profiles
      closer to constant spatial equi-affine speed than to constant Euclidean speed,
      with path torsion (i.e., local deviation from planarity) directly affecting the
      speed profiles perceived as most uniform, as predicted for constant spatial equi
      affine speed. This demonstrates the dominance of equi-affine geometry in spatial
      motion perception. However, constant equi-affine speed did not fully account for
      the variability among the speed profiles selected as most uniform for different
      shapes. Moreover, in a followup experiment, we found that viewing distance
      affected the speed profile reported as most uniform for the extensively studied
      planar elliptical motion paths. These findings provide evidence for the critical
      role of equi-affine geometry in spatial motion perception and contribute to the
      mounting evidence for the role of non-Euclidean geometries in motion perception
      and production. 

PMID- 24108796
TI  - An auditory colliculothalamocortical brain slice preparation in mouse.
AB  - Key questions about the thalamus are still unanswered in part because of the
      inability to stimulate its inputs while monitoring cortical output. To address
      this, we employed flavoprotein autofluorescence optical imaging to expedite the
      process of developing a brain slice in mouse with connectivity among the auditory
      midbrain, thalamus, thalamic reticular nucleus, and cortex. Optical,
      electrophysiological, anatomic, and pharmacological tools revealed ascending
      connectivity from midbrain to thalamus and thalamus to cortex as well as
      descending connectivity from cortex to thalamus and midbrain and from thalamus to
      midbrain. The slices were relatively thick (600-700 MUm), but, based on typical
      measures of cell health (resting membrane potential, spike height, and input
      resistance) and use of 2,3,5-triphenyltetrazolium chloride staining, the slices
      were as viable as thinner slices. As expected, after electrical stimulation of
      the midbrain, the latency of synaptic responses gradually increased from thalamus
      to cortex, and spiking responses were seen in thalamic neurons. Therefore, for
      the first time, it will be possible to manipulate and record simultaneously the
      activity of most of the key brain structures that are synaptically connected to
      the thalamus. The details for the construction of such slices are described
      herein. 

PMID- 24108798
TI  - Sharp wave-associated synchronized inputs from the piriform cortex activate
      olfactory tubercle neurons during slow-wave sleep.
AB  - During slow-wave sleep, anterior piriform cortex neurons show highly synchronized
      discharges that accompany olfactory cortex sharp waves (OC-SPWs). The OC-SPW
      related synchronized activity of anterior piriform cortex neurons travel down to
      the olfactory bulb and is thought to be involved in the reorganization of bulbar
      neuronal circuitry. However, influences of the OC-SPW-related activity on other
      regions of the central olfactory system are still unknown. Olfactory tubercle is
      an area of OC and part of ventral striatum that plays a key role in reward
      directed motivational behaviors. In this study, we show that in freely behaving
      rats, olfactory tubercle receives OC-SPW-associated synchronized inputs during
      slow-wave sleep. Local field potentials in the olfactory tubercle showed SPW-like
      activities that were in synchrony with OC-SPWs. Single-unit recordings showed
      that a subpopulation of olfactory tubercle neurons discharged in synchrony with
      OC-SPWs. Furthermore, correlation analysis of spike activity of anterior piriform
      cortex and olfactory tubercle neurons revealed that the discharges of anterior
      piriform cortex neurons tended to precede those of olfactory tubercle neurons.
      Current source density analysis in urethane-anesthetized rats indicated that the
      current sink of the OC-SPW-associated input was located in layer III of the
      olfactory tubercle. These results indicate that OC-SPW-associated synchronized
      discharges of piriform cortex neurons travel to the deep layer of the olfactory
      tubercle and drive discharges of olfactory tubercle neurons. The entrainment of
      olfactory tubercle neurons in the OC-SPWs suggests that OC-SPWs coordinate
      reorganization of neuronal circuitry across wide areas of the central olfactory
      system including olfactory tubercle during slow-wave sleep. 

PMID- 24108799
TI  - Neural conflict-control mechanisms improve memory for target stimuli.
AB  - According to conflict-monitoring models, conflict serves as an internal signal
      for reinforcing top-down attention to task-relevant information. While evidence
      based on measures of ongoing task performance supports this idea, implications
      for long-term consequences, that is, memory, have not been tested yet. Here, we
      evaluated the prediction that conflict-triggered attentional enhancement of
      target-stimulus processing should be associated with superior subsequent memory
      for those stimuli. By combining functional magnetic resonance imaging (fMRI) with
      a novel variant of a face-word Stroop task that employed trial-unique face
      stimuli as targets, we were able to assess subsequent (incidental) memory for
      target faces as a function of whether a given face had previously been
      accompanied by congruent, neutral, or incongruent (conflicting) distracters. In
      line with our predictions, incongruent distracters not only induced behavioral
      conflict, but also gave rise to enhanced memory for target faces. Moreover,
      conflict-triggered neural activity in prefrontal and parietal regions was
      predictive of subsequent retrieval success, and displayed conflict-enhanced
      functional coupling with medial-temporal lobe regions. These data provide support
      for the proposal that conflict evokes enhanced top-down attention to task
      relevant stimuli, thereby promoting their encoding into long-term memory. Our
      findings thus delineate the neural mechanisms of a novel link between cognitive
      control and memory. 

PMID- 24108801
TI  - Unconscious presentation of fearful face modulates electrophysiological responses
      to emotional prosody.
AB  - Cross-modal integration of visual and auditory emotional cues is supposed to be
      advantageous in the accurate recognition of emotional signals. However, the
      neural locus of cross-modal integration between affective prosody and
      unconsciously presented facial expression in the neurologically intact population
      is still elusive at this point. The present study examined the influences of
      unconsciously presented facial expressions on the event-related potentials (ERPs)
      in emotional prosody recognition. In the experiment, fearful, happy, and neutral
      faces were presented without awareness by continuous flash suppression
      simultaneously with voices containing laughter and a fearful shout. The
      conventional peak analysis revealed that the ERPs were modulated interactively by
      emotional prosody and facial expression at multiple latency ranges, indicating
      that audio-visual integration of emotional signals takes place automatically
      without conscious awareness. In addition, the global field power during the late
      latency range was larger for shout than for laughter only when a fearful face was
      presented unconsciously. The neural locus of this effect was localized to the
      left posterior fusiform gyrus, giving support to the view that the cortical
      region, traditionally considered to be unisensory region for visual processing,
      functions as the locus of audiovisual integration of emotional signals. 

PMID- 24108800
TI  - Cell type-specific effects of adenosine on cortical neurons.
AB  - The neuromodulator adenosine is widely considered to be a key regulator of sleep
      homeostasis and an indicator of sleep need. Although the effect of adenosine on
      subcortical areas has been previously described, the effects on cortical neurons
      have not been addressed systematically to date. To that purpose, we performed in
      vitro whole-cell patch-clamp recordings and biocytin staining of pyramidal
      neurons and interneurons throughout all layers of rat prefrontal and
      somatosensory cortex, followed by morphological analysis. We found that
      adenosine, via the A1 receptor, exerts differential effects depending on neuronal
      cell type and laminar location. Interneurons and pyramidal neurons in layer 2 and
      a subpopulation of layer 3 pyramidal neurons that displayed regular spiking were
      insensitive to adenosine application, whereas other pyramidal cells in layers 3-6
      were hyperpolarized (range 1.2-10.8 mV). Broad tufted pyramidal neurons with
      little spike adaptation showed a small adenosine response, whereas slender tufted
      pyramidal neurons with substantial adaptation showed a bigger response. These
      studies of the action of adenosine at the postsynaptic level may contribute to
      the understanding of the changes in cortical circuit functioning that take place
      between sleep and awakening. 

PMID- 24108802
TI  - Disrupted effective connectivity between the amygdala and orbitofrontal cortex in
      social anxiety disorder during emotion discrimination revealed by dynamic causal
      modeling for FMRI.
AB  - Social anxiety disorder (SAD) is characterized by over-reactivity of fear-related
      circuits in social or performance situations and associated with marked social
      impairment. We used dynamic causal modeling (DCM), a method to evaluate effective
      connectivity, to test our hypothesis that SAD patients would exhibit dysfunctions
      in the amygdala-prefrontal emotion regulation network. Thirteen unmedicated SAD
      patients and 13 matched healthy controls performed a series of facial emotion and
      object discrimination tasks while undergoing fMRI. The emotion-processing network
      was identified by a task-related contrast and motivated the selection of the
      right amygdala, OFC, and DLPFC for DCM analysis. Bayesian model averaging for DCM
      revealed abnormal connectivity between the OFC and the amygdala in SAD patients.
      In healthy controls, this network represents a negative feedback loop. In
      patients, however, positive connectivity from OFC to amygdala was observed,
      indicating an excitatory connection. As we did not observe a group difference of
      the modulatory influence of the FACE condition on the OFC to amygdala connection,
      we assume a context-independent reduction of prefrontal control over amygdalar
      activation in SAD patients. Using DCM, it was possible to highlight not only the
      neuronal dysfunction of isolated brain regions, but also the dysbalance of a
      distributed functional network. 

PMID- 24108804
TI  - Capturing with EEG the neural entrainment and coupling underlying sensorimotor
      synchronization to the beat.
AB  - Synchronizing movements with rhythmic inputs requires tight coupling of sensory
      and motor neural processes. Here, using a novel approach based on the recording
      of steady-state-evoked potentials (SS-EPs), we examine how distant brain areas
      supporting these processes coordinate their dynamics. The electroencephalogram
      was recorded while subjects listened to a 2.4-Hz auditory beat and tapped their
      hand on every second beat. When subjects tapped to the beat, the EEG was
      characterized by a 2.4-Hz SS-EP compatible with beat-related entrainment and a
      1.2-Hz SS-EP compatible with movement-related entrainment, based on the results
      of source analysis. Most importantly, when compared with passive listening of the
      beat, we found evidence suggesting an interaction between sensory- and motor
      related activities when subjects tapped to the beat, in the form of (1)
      additional SS-EP appearing at 3.6 Hz, compatible with a nonlinear product of
      sensorimotor integration; (2) phase coupling of beat- and movement-related
      activities; and (3) selective enhancement of beat-related activities over the
      hemisphere contralateral to the tapping, suggesting a top-down effect of movement
      related activities on auditory beat processing. Taken together, our results are
      compatible with the view that rhythmic sensorimotor synchronization is supported
      by a dynamic coupling of sensory and motor related activities.

PMID- 24108803
TI  - Refinement but not maintenance of visual receptive fields is independent of
      visual experience.
AB  - Visual deprivation is reported to prevent or delay the development of mature
      receptive field (RF) properties in primary visual cortex (V1) in several species.
      In contrast, visual deprivation neither prevents nor delays refinement of RF size
      in the superior colliculus (SC) of Syrian hamsters, although vision is required
      for RF maintenance in the SC. Here, we report that, contrary to expectation,
      visual cortical RF refinement occurs normally in dark-reared animals. As in the
      SC, a brief period of visual experience is required to maintain V1 RF refinement
      in adulthood. Whereas in the SC, 3 days of visual experience within a sensitive
      period (P37-40) was sufficient to protect RFs from deprivation-induced
      enlargement in adulthood, 7 days (P33-40) were required for RF size maintenance
      in V1. Thus, spontaneous activity is sufficient for RF refinement at these 2
      levels of the visual pathway, and visual input is necessary only to prevent
      deprivation-induced RF enlargement in adulthood. These studies show that sensory
      experience during a late juvenile sensitive period protects the visual pathway
      against sensory deprivation in adulthood, and suggest that more importance may
      have been placed on the role of early visual experience in visual RF development
      than is warranted. 

PMID- 24108805
TI  - Facilitation of synaptic transmission in the anterior cingulate cortex in
      viscerally hypersensitive rats.
AB  - Electrophysiological studies have shown the enhanced response of anterior
      cingulate cortex (ACC) to colorectal distension in viscerally hypersensitive (VH)
      rats, which can be observed up to 7 weeks following colonic anaphylaxis,
      independent of colon inflammation, suggesting a mechanism for learning and
      triggering of pain memories in the ACC neuronal circuitry. Activity-dependent
      plasticity in synaptic strength may serve as a key mechanism that reflects
      cortical plasticity. However, only a few reports have indicated the synaptic
      plasticity of ACC in vivo. In the present study, electrophysiological recording
      showed long-lasting potentiation of local field potential in the medial thalamus
      (MT)-ACC synapses in VH rats. Theta burst stimulation in the MT reliably induced
      long-term potentiation in the MT-ACC pathway in normal rats, but was occluded in
      the VH state. Further, repeated tetanization of MT increased ACC neuronal
      activity and visceral pain responses of normal rats, mimicking VH rats. In
      conclusion, we demonstrated for the first time that visceral hypersensitivity is
      associated with alterations of synaptic plasticity in the ACC. The ACC synaptic
      strengthening in chronic visceral pain may engage signal transduction pathways
      that are in common with those activated by electrical stimulation, and serves as
      an attractive cellular model of functional visceral pain. 

PMID- 24108807
TI  - Morphological and physiological characterization of pyramidal neuron subtypes in
      rat medial prefrontal cortex.
AB  - The medial prefrontal cortex (mPFC) has been implicated in cognitive and
      executive processes including decision making, working memory and behavioral
      flexibility. Cortical processing depends on the interaction between distinct
      neuronal cell types in different cortical layers. To better understand cortical
      processing in the rat mPFC, we studied the diversity of pyramidal neurons using
      in vitro whole-cell patch clamp recordings and biocytin staining of neurons,
      followed by morphological analysis. Using unsupervised cluster analysis for the
      objective grouping of neurons, we identified more than 10 different pyramidal
      subtypes spread across the different cortical layers. Layer 2 pyramidal neurons
      possessed a unique morphology with wide apical dendritic field spans and a narrow
      basal field span. Layer 3 contained the only subtype that showed a burst of
      action potentials upon current injection. Layer 5 pyramidal neurons showed the
      largest voltage sags. Finally, pyramidal neurons in layer 6 (L6) showed a great
      variety in their morphology with 39% of L6 neurons possessing tall apical
      dendrites that extend into layer 1. Future experiments on the functional role of
      the mPFC should take into account the great diversity of pyramidal neurons. 

PMID- 24108806
TI  - Visual cortical gamma-band activity during free viewing of natural images.
AB  - Gamma-band activity in visual cortex has been implicated in several cognitive
      operations, like perceptual grouping and attentional selection. So far, it has
      been studied primarily under well-controlled visual fixation conditions and using
      well-controlled stimuli, like isolated bars or patches of grating. If gamma-band
      activity is to subserve its purported functions outside of the laboratory, it
      should be present during natural viewing conditions. We recorded neuronal
      activity with a 252-channel electrocorticographic (ECoG) grid covering large
      parts of the left hemisphere of 2 macaque monkeys, while they freely viewed
      natural images. We found that natural viewing led to pronounced gamma-band
      activity in the visual cortex. In area V1, gamma-band activity during natural
      viewing showed a clear spectral peak indicative of oscillatory activity between
      50 and 80 Hz and was highly significant for each of 65 natural images. Across the
      ECoG grid, gamma-band activity during natural viewing was present over most of
      the recorded visual cortex and absent over most remaining cortex. After saccades,
      the gamma peak frequency slid down to 30-40 Hz at around 80 ms postsaccade, after
      which the sustained 50- to 80-Hz gamma-band activity resumed. We propose that
      gamma-band activity plays an important role during natural viewing. 

PMID- 24108808
TI  - Predicting planning performance from structural connectivity between left and
      right mid-dorsolateral prefrontal cortex: moderating effects of age during
      postadolescence and midadulthood.
AB  - Complex cognitive abilities such as planning are known to critically rely on
      activity of bilateral mid-dorsolateral prefrontal cortex (mid-dlPFC). However,
      the functional relevance of the structural connectivity between left and right
      mid-dlPFC is yet unknown. Here, we applied global tractography to derive
      streamline counts as estimates of the structural connectivity between mid-dlPFC
      homologs and related it to planning performance in the Tower of London task
      across early to midadulthood, assuming a moderating effect of age. Multiple
      regression analyses with interaction effects revealed that streamline counts
      between left and right mid-dlPFC were negatively associated with planning
      performance specifically in early postadolescence. From the fourth life decade
      on, there was a trend for a reversed, positive association. These differential
      findings were corroborated by converging results from fractional anisotropy and
      white-matter density estimates in the genu of the corpus callosum where fibers
      connecting mid-dlPFC homologs traversed. Moreover, the results for streamline
      counts were regionally specific, marking the strength of mid-dlPFC connectivity
      as critical in predicting interindividual differences in planning performance
      across different stages of adulthood. Taken together, present findings provide
      first evidence for nonadditive effects of age on the relation between complex
      cognitive abilities and the structural connectivity of mid-dlPFC homologs. 

PMID- 24108809
TI  - Selective permeabilization of the blood-brain barrier at sites of metastasis.
AB  - BACKGROUND: Effective chemotherapeutics for primary systemic tumors have limited
      access to brain metastases because of the blood-brain barrier (BBB). The aim of
      this study was to develop a strategy for specifically permeabilizing the BBB at
      sites of cerebral metastases. METHODS: BALB/c mice were injected intracardially
      to induce brain metastases. After metastasis induction, either tumor necrosis
      factor (TNF) or lymphotoxin (LT) was administered intravenously, and 2 to 24
      hours later gadolinium- diethylenetriaminepentaacetic acid, horseradish
      peroxidase, or radiolabeled trastuzumab ((111)In-BnDTPA-Tz) was injected
      intravenously. BBB permeability was assessed in vivo using gadolinium-enhanced T1
      weighted magnetic resonance imaging and confirmed histochemically. Brain uptake
      of (111)In-BnDTPA-Tz was determined using in vivo single photon emission computed
      tomography/computed tomography. Endothelial expression of TNF receptors was
      determined immunohistochemically in both mouse and human brain tissue containing
      metastases. Group differences were analyzed with one-way analysis of variance
      followed by post hoc tests, Wilcoxon signed rank test, and Kruskal-Wallis with
      Dunn's multiple comparison test. All statistical tests were two-sided. RESULTS:
      Localized expression of TNF receptor 1 (TNFR1) was evident on the vascular
      endothelium associated with brain metastases. Administration of TNF or LT
      permeabilized the BBB to exogenous tracers selectively at sites of brain
      metastasis, with peak effect at 6 hours. Metastasis-specific uptake ratio of
      (111)In-BnDTPA-Tz was also demonstrated after systemic TNF administration vs
      control (0.147+/-0.066 vs 0.001+/-0.001). Human brain metastases displayed a
      similar TNF receptor profile compared with the mouse model, with predominantly
      vascular TNFR1 expression. CONCLUSIONS: These findings describe a new approach to
      selectively permeabilize the BBB at sites of brain metastases to aid in detection
      of micrometastases and facilitate tumor-specific access of chemotherapeutic
      agents. We hypothesize that this permeabilization works primarily though TNFR1
      activation and has the potential for clinical translation.

PMID- 24108810
TI  - Justifying the choice of endpoints for clinical trials.

PMID- 24108811
TI  - Progression-free survival as a surrogate for overall survival in
      advanced/recurrent gastric cancer trials: a meta-analysis.
AB  - The traditional endpoint for assessing efficacy of chemotherapies for
      advanced/recurrent gastric cancer is overall survival (OS), but OS requires
      prolonged follow-up. We investigated whether progression-free survival (PFS) is a
      valid surrogate for OS. Using individual patient data from the GASTRIC meta
      analysis, surrogacy of PFS was assessed through the correlation between the
      endpoints and through the correlation between the treatment effects on the
      endpoints. External validation of the prediction based on PFS was also evaluated.
      Individual data from 4069 patients in 20 randomized trials were analyzed. The
      rank correlation coefficient between PFS and OS was 0.853 (95% confidence
      interval [CI] = 0.852 to 0.854). The R (2) between treatment effects on PFS and
      on OS was 0.61 (95% CI = 0.04 to 1.00). Treatment effects on PFS and on OS were
      only moderately correlated, and we could not confirm the validity of PFS as a
      surrogate endpoint for OS in advanced/recurrent gastric cancer. 

PMID- 24108812
TI  - Disease-free survival as a surrogate for overall survival in adjuvant trials of
      gastric cancer: a meta-analysis.
AB  - BACKGROUND: In investigations of the effectiveness of surgery and adjuvant
      chemotherapy for gastric cancers, overall survival (OS) is considered the gold
      standard endpoint. However, the disadvantage of using OS as the endpoint is that
      it requires an extended follow-up period. We sought to investigate whether
      disease-free survival (DFS) is a valid surrogate for OS in trials of adjuvant
      chemotherapy for gastric cancer. METHODS: The GASTRIC group initiated a meta
      analysis of individual patient data collected in randomized clinical trials
      comparing adjuvant chemotherapy vs surgery alone for patients with curatively
      resected gastric cancer. Surrogacy of DFS was assessed through the correlation
      between the endpoints as well as through the correlation between the treatment
      effects on the endpoints. External validation of the prediction based on DFS was
      also evaluated. RESULTS: Individual patient data from 14 randomized clinical
      trials that included a total of 3288 patients were analyzed. The rank correlation
      coefficient between DFS and OS was 0.974 (95% confidence interval [CI] = 0.971 to
      0.976). The coefficient of determination between the treatment effects on DFS and
      on OS was as high as 0.964 (95% CI = 0.926 to 1.000), and the surrogate threshold
      effect based on adjusted regression analysis was 0.92. In external validation,
      the six hazard ratios for OS predicted according to DFS were in very good
      agreement with those actually observed for OS. CONCLUSIONS: DFS is an acceptable
      surrogate for OS in trials of cytotoxic agents for gastric cancer in the adjuvant
      setting.

PMID- 24108813
TI  - Comparison of positively and negatively charged achiral co-monomers added to
      cyclodextrin monolith: improved chiral separations in capillary
      electrochromatography.
AB  - Cyclodextrins (CDs) and their derivatives have been one of the most popular and
      successful chiral additives used in electrokinetic chromatography because of the
      presence of multiple chiral centers, which leads to multiple chiral interactions.
      However, there has been relatively less published work on the use of CDs as
      monolithic media for capillary electrochromatography (CEC). The goal of this
      study was to show how the addition of achiral co-monomer to a polymerizable CD
      such as glycidyl methacrylate beta-cyclodextrin (GMA/beta-CD) can affect the
      enantioselective separations in monolithic CEC. To achieve this goal, polymeric
      monoliths columns were prepared by co-polymerizing GMA/beta-CD with cationic or
      anionic achiral co-monomers [(2-acrylamido-2-methyl-1-propanesulfonic acid (AMPS)
      and vinyl benzyltrimethyl-ammonium (VBTA)] in the presence of conventional
      crosslinker (ethylene dimethacrylate) and ternary porogen system including
      butanediol, propanol and water. A total of 34 negatively charged compounds, 30
      positively charged compounds and 33 neutral compounds were screened to compare
      the enantioresolution capability on the GMA/beta-CD, GMA/beta-CD-VBTA and
      GMA/beta-CD-AMPS monolithic columns. 

PMID- 24108814
TI  - Development of a sensitive HPTLC method for quantification of nimbolide in
      Azadirachta indica and its dosage form.
AB  - An improved and sensitive High Performance Thin-Layer Chromatography (HPTLC)
      method has been developed for determination of anticancer compound, nimbolide in
      different parts of Azadirachta indica and its dosage form. A quick and simple
      ultrasonication technique was used for the preparation of sample solutions.
      Separation of the components was achieved on precoated TLC plates by using
      optimized tertiary mobile phase consisting of n-hexane:ethyl acetate:acetic acid
      (6:4:0.2, v/v/v) with a solvent migration distance of 68 mm. Densitometric
      quantification was performed after derivatization of the plate with methanol
      sulfuric acid reagent in reflection/absorption mode at 515 nm. A linear response
      of nimbolide was obtained over the range of 200-1400 ng/spot with a correlation
      coefficient of r(2) = 0.99968, indicating good relationship between concentration
      and peak area. The method sensitivity was found to be increased by performing the
      analysis after derivatization with methanol-sulfuric acid reagent. The limit of
      detection and limit of quantification were found to be 70 and 200 ng/spot,
      respectively. The obtained recovery range from 96.70 to 98.01% with an average of
      97.46% proves excellent accuracy of the method. ICH protocol was followed for
      validation of the HPTLC method in terms of precision, repeatability and accuracy.
      The developed method was found to be highly sensitive and the mobile phase
      efficiently separated nimbolide from other components. The maximum content of
      nimbolide was found in leaves. Further, the developed HPTLC method can be applied
      successfully for the marker evaluation of the formulations containing A. indica. 

PMID- 24108862
TI  - Hypertension control in community health centers across China: analysis of
      antihypertensive drug treatment patterns.
AB  - BACKGROUND: Blood pressure (BP) control in China is generally poor. It is assumed
      that an important cause of this unsatisfactory situation is the present standard
      of care provided by primary care physicians. METHODS: One thousand community
      health centers (CHCs) were selected across China based on geographical location,
      previous cooperative experience, and acceptance of an invitation to implement a
      standardized protocol of community-based BP management. Baseline information for
      each hypertensive patient under the care of these CHCs was collected, and the
      present pattern of hypertensive drug treatment was analyzed. RESULTS: Of all
      identified hypertensive patients (n = 249,830), 37% were treated with drugs.
      Characteristics linked with hypertension treatment included systolic BP, age,
      sex, region, smoking and alcohol consumption status, body mass index,
      comorbidities, and family history. The most frequently prescribed classes of
      antihypertensive drugs were diuretics (56.0%), followed by centrally active drugs
      (CADs) (38.3%), calcium channel blockers (CCBs) (36.8%), vasodilators (26.5%),
      and angiotensin-converting enzyme inhibitors (ACEIs) (23.3%). In regards to drug
      combination patterns, diuretics plus CADs was the most frequently used 2-drug
      combination (61.4%) and vasodilators plus CADs plus diuretics was the most
      frequently used 3-drug therapy (69.2%). Seventy-seven percent of patients on
      combination therapy were prescribed single pill combinations, 87.2% of which were
      composed of CADs and vasodilators and 12.8% of which were composed of ACEIs and
      diuretics. The control rates of patients on monotherapy and combination therapy
      were 27.7% and 24.1% (P < 0.05), respectively. CONCLUSIONS: Our study identified
      major shortcomings in the present status of antihypertensive pharmacotherapy in
      routine medical practice in China. It is essential to implement a program of
      professional education regarding the appropriate use of antihypertensive drugs.

PMID- 24108863
TI  - U-shaped relationship of left ventricular ejection time index and all-cause
      mortality.
AB  - BACKGROUND: Previous studies have suggested that systolic and diastolic heart
      failure is associated with alterations of left ventricular ejection time index
      (LVETI). We sought to examine the relation of LVETI to mortality in an elderly
      population. METHODS: We prospectively enrolled 852 patients undergoing cardiac
      catheterization for suspected coronary artery disease (CAD) in 2001 and 2002.
      LVETI was measured noninvasively using radial applantation tonometry and pulse
      waveform analysis. Mortality data were assessed by telephone interviews with
      general practitioners, hospital records, and the national mortality register.
      RESULTS: The mean age was 64.8 years, 60.7% of subjects were men, 70.1% of
      subjects had significant CAD, and 28.6% of subjects had impaired systolic
      function. After a mean follow-up of 8.2 +/- 2.3 years, 183 deaths occurred. At
      baseline, LVETI was significantly associated with age, systolic and diastolic
      blood pressure, pulse pressure, and N-terminal probrain natriuretic peptide. A
      shorter LVETI was significantly and independently associated with impaired
      systolic function. Kaplan-Meier analysis revealed that both prolonged and
      shortened ejection time index (1st and 3rd tertile LVETI) were associated with a
      decreased survival probability (P <0.05, log-rank-test) compared with normal
      LVETI (2nd tertile). In multivariable Cox regression analysis, the hazard ratios
      for all-cause mortality were 1.66 for 1st tertile LVETI (P = 0.01) and 1.75 for
      3rd tertile LVETI (P = 0.006). The effect of a shortened LVETI on mortality was
      partly due to the effect of impaired systolic function on ejection duration.
      CONCLUSIONS: We observed a U-shaped relation between ejection duration and all
      cause mortality.

PMID- 24108864
TI  - Blood pressure and cardiovascular mortality in dialysis patients with left
      ventricular systolic dysfunction.
AB  - BACKGROUND: In patients chronically treated with hemodialysis, the prevalence of
      heart failure is high with a consequently poor prognosis. The role played by
      blood pressure (BP) on cardiovascular (CV) mortality of these patients has not
      been clearly defined. METHODS: In this follow-up study, we investigated the
      relationship of pre- and postdialysis measurements of BP with CV and all-cause
      mortality in a cohort of 557 dialysis patients with a left ventricular (LV)
      ejection fraction <50%. RESULTS: During the follow-up (mean = 21.6 +/- 8.8
      months), 179 deaths were recorded. Ninety-eight patients died from CV causes. By
      the Cox multivariable analysis, we constructed a predictive model of CV mortality
      including age, duration on dialysis, diabetes, serum albumin, diffusive dialysis
      technique, predialysis mean arterial pressure (MAP) (hazard ratio (HR) = 0.978;
      95% confidence interval (CI) = 0.956-0.999), and postdialysis MAP (HR = 1.035;
      95% CI = 1.010-1.061). The relationship with mortality was inverse for
      predialysis MAP and direct for postdialysis MAP. In a subsequent analysis, we
      found that pre- and postdialysis systolic BP, but not diastolic BP, were
      predictive of CV mortality. Predialysis MAP was in a direct relationship with
      body mass index. Postdialysis MAP had an inverse relationship with weight loss
      during dialysis session. CONCLUSIONS: CV mortality in dialysis patients with LV
      dysfunction is associated with both pre- and postdialysis BP interacting in a
      complex relationship. Nutritional state and fluid balance and removal are
      possible clues to this relationship.

PMID- 24108865
TI  - Tubulin acetylation a valuable accessory of the platelet cytoskeleton. Focus on
      "Histone deacetylase 6-mediated deacetylation of alpha-tubulin coordinates
      cytoskeletal and signaling events during platelet activation".

PMID- 24108866
TI  - Molecular mechanisms of dysautonomia during heart failure. Focus on "Heart
      failure-induced changes of voltage-gated Ca2+ channels and cell excitability in
      rat cardiac postganglionic neurons".

PMID- 24108868
TI  - Temperature influences neuronal activity and CO2/pH sensitivity of locus
      coeruleus neurons in the bullfrog, Lithobates catesbeianus.
AB  - The locus coeruleus (LC) is a chemoreceptive brain stem region in anuran
      amphibians and contains neurons sensitive to physiological changes in CO2/pH. The
      ventilatory and central sensitivity to CO2/pH is proportional to the temperature
      in amphibians, i.e., sensitivity increases with increasing temperature. We
      hypothesized that LC neurons from bullfrogs, Lithobates catesbeianus, would
      increase CO2/pH sensitivity with increasing temperature and decrease CO2/pH
      sensitivity with decreasing temperature. Further, we hypothesized that cooling
      would decrease, while warming would increase, normocapnic firing rates of LC
      neurons. To test these hypotheses, we used whole cell patch-clamp
      electrophysiology to measure firing rate, membrane potential (V(m)), and input
      resistance (R(in)) in LC neurons in brain stem slices from adult bullfrogs over a
      physiological range of temperatures during normocapnia and hypercapnia. We found
      that cooling reduced chemosensitive responses of LC neurons as temperature
      decreased until elimination of CO2/pH sensitivity at 10 degrees C. Chemosensitive
      responses increased at elevated temperatures. Surprisingly, chemosensitive LC
      neurons increased normocapnic firing rate and underwent membrane depolarization
      when cooled and decreased normocapnic firing rate and underwent membrane
      hyperpolarization when warmed. These responses to temperature were not observed
      in nonchemosensitive LC neurons or neurons in a brain stem slice 500 MUm rostral
      to the LC. Our results indicate that modulation of cellular chemosensitivity
      within the LC during temperature changes may influence temperature-dependent
      respiratory drive during acid-base disturbances in amphibians. Additionally, cold
      activated/warm-inhibited LC neurons introduce paradoxical temperature sensitivity
      in respiratory control neurons of amphibians.

PMID- 24108867
TI  - Combined acute hyperglycemic and hyperinsulinemic clamp induced profibrotic and
      proinflammatory responses in the kidney.
AB  - Increase in matrix protein content in the kidney is a cardinal feature of
      diabetic kidney disease. While renal matrix protein content is increased by
      chronic hyperglycemia, whether it is regulated by acute elevation of glucose and
      insulin has not been addressed. In this study, we aimed to evaluate whether short
      duration of combined hyperglycemia and hyperinsulinemia, mimicking the metabolic
      environment of prediabetes and early type 2 diabetes, induces kidney injury.
      Normal rats were subjected to either saline infusion (control, n = 4) or 7 h of
      combined hyperglycemic-hyperinsulinemic clamp (HG+HI clamp; n = 6). During the
      clamp, plasma glucose and plasma insulin were maintained at about 350 mg/dl and
      16 ng/ml, respectively. HG+HI clamp increased the expression of renal cortical
      transforming growth factor-beta (TGF-beta) and renal matrix proteins, laminin and
      fibronectin. This was associated with the activation of SMAD3, Akt, mammalian
      target of rapamycin (mTOR) complexes, and ERK signaling pathways and their
      downstream target events in the initiation and elongation phases of mRNA
      translation, an important step in protein synthesis. Additionally, HG+HI clamp
      provoked renal inflammation as shown by the activation of Toll-like receptor 4
      (TLR4) and infiltration of CD68-positive monocytes. Urinary F2t isoprostane
      excretion, an index of renal oxidant stress, was increased in the HG+HI clamp
      rats. We conclude that even a short duration of hyperglycemia and
      hyperinsulinemia contributes to activation of pathways that regulate matrix
      protein synthesis, inflammation, and oxidative stress in the kidney. This finding
      could have implications for the control of short-term rises in blood glucose in
      diabetic individuals at risk of developing kidney disease. 

PMID- 24108869
TI  - Daily exposure to a running wheel entrains circadian rhythms in mice in parallel
      with development of an increase in spontaneous movement prior to running-wheel
      access.
AB  - Entrainment of circadian behavior rhythms by daily exposure to a running wheel
      was examined in mice under constant darkness. Spontaneous movement was
      individually monitored for more than 6 mo by a thermal sensor. After
      establishment of steady-state free running, mice were placed in a different cage
      equipped with a running-wheel for 3 h once per day at 6 AM. The daily exchange
      was continued for 80 days. The number of wheel revolutions during exposure to the
      running wheel was also measured simultaneously with spontaneous movement. In 13
      out of 17 mice, circadian behavior rhythm was entrained by daily wheel exposure,
      showing a period indistinguishable from 24 h. The entrainment occurred in
      parallel with an increase in spontaneous movement immediately prior to the daily
      wheel exposure. A similar preexposure increase was observed in only one of four
      nonentrained mice. The preexposure increase appeared in 19.5 days on average
      after the start of daily wheel exposure and persisted for 36 days on average
      after the termination of the exposure schedule. The preexposure increase was
      detected only when daily wheel exposure came into the activity phase of the
      circadian behavior rhythm, which was accompanied by an increase in the number of
      wheel revolutions. These findings indicate that a novel oscillation with a
      circadian period is induced in mice by daily exposure to a running wheel at a
      fixed time of day and suggest that the oscillation is involved in the nonphotic
      entrainment of circadian rhythms in spontaneous movement. 

PMID- 24109089
TI  - Estrogens downregulate urocortin 2 expression in rat uterus.
AB  - Urocortin 2 (Ucn2) is a member of the corticotropin-releasing factor peptide
      family and is expressed by various tissues, including reproductive tissues such
      as the uterus, ovary, and placenta. However, the regulatory mechanisms of Ucn2
      expression and the physiological significance of Ucn2 in these tissues remain
      unclear. We previously showed that passive immunization of immature female rats
      by i.p. injection of anti-Ucn2 IgG induces earlier onset of puberty. Therefore,
      this study was designed to clarify the site and regulatory mechanisms of Ucn2
      expression in the uterus. Expression levels of Ucn2 mRNA in the uterus were
      higher in immature (2- and 4-week-old) and aged (17-month-old) rats than in
      mature (9-week-old) rats in the proestrus phase. In 9-week-old rats, mRNA
      expression levels and contents in the uterus were lower in the proestrus phase
      than in the diestrus phase, while plasma Ucn2 concentrations did not differ
      between the two phases. Ucn2-like immunoreactivitiy was detected in the
      endometrial gland epithelial cells of the uterus. S.c. injection of estradiol
      benzoate or an estrogen receptor alpha (ERalpha) agonist significantly reduced
      mRNA expression levels and contents of Ucn2 in the uterus when compared with
      vehicle-injected ovariectomized rats. By contrast, estradiol benzoate increased
      Ucn2 mRNA expression levels in the lung. Thus, estrogens downregulate Ucn2
      expression in the uterus in a tissue-specific manner, and Ucn2 may play a role in
      the regulatory mechanisms of maturation of the uterus through ERalpha and estrous
      cycle. 

PMID- 24109090
TI  - Patient needs from general practice following a traumatic injury: a qualitative
      study using narrative interviews with British service personnel.
AB  - OBJECTIVES: To explore the first period of sick leave in military patients
      following a traumatic battle injury, and the role of primary care. To identify if
      and where patients perceived difficulties. METHOD: Participants were recruited
      from The Defence Medical Rehabilitation Centre (DMRC) Headley Court on their
      second admission. Purposive sampling was used to access a range of different
      injuries and experiences. Nine patients were interviewed at DMRC where they were
      asked to recount their stories throughout rehabilitation. Thematic and structural
      analysis of the narrative accounts was applied. RESULTS: The majority of problems
      encountered by the participants occurred during their initial period of sick
      leave between Royal Centre for Defence Medicine (RCDM), Queen Elizabeth Hospital,
      Birmingham, and DMRC. Participants often had difficulty identifying who to
      contact if they had a problem on sick leave, with many ringing secondary care
      directly. Time spent travelling to medical reviews was identified as affecting
      the quality of leave. CONCLUSIONS: There is a need for greater patient
      understanding regarding whom to contact should they develop problems while on
      sick leave. A patient passport containing all discharge documentation and
      simplified contact details may help reduce patient confusion regarding whom to
      contact. GPs require greater awareness and understanding of the complexity of
      these patients' injuries and the need for early secondary care review to prevent
      delayed or inappropriate admissions. Most problems that patients face will occur
      on their first period of sick leave. Reducing the time spent on sick leave before
      admission to DMRC would limit the likelihood of problems occurring at this high
      risk time.

PMID- 24109091
TI  - A pilot study of an enhanced mental health assessment during routine and
      discharge medicals in the British Armed Forces.
AB  - OBJECTIVES: A pilot study to assess the practicality of introducing an enhanced
      mental health assessment (EMHA) into all routine and discharge medicals of the UK
      Armed Forces in order to facilitate treatment prior to and on return to civilian
      life. METHODS: A pilot study was conducted using an EMHA questionnaire with
      questions about depression, anxiety, post-traumatic stress disorder, alcohol use,
      sleep and anger/irritability. At pilot sites, the EMHA was completed during all
      routine and discharge medicals between May 2011 and July 2011. At the end of the
      study period, qualitative data were collected from participating medical officers
      and practice managers regarding their opinions about the pilot study. RESULTS:
      The quantitative data revealed an average pick-up rate for mental health (MH)
      problems. Out of the four military medical centres who participated and the 325
      questionnaires collected, one referral to a Department of Community Mental Health
      was made. 26 (8%) patients were categorised as 'some concern and patient offered
      advice and/or reassurance'. The vast majority of patients were found to have no
      evidence of MH problems. However, using a validated alcohol screening tool, 64%
      of service personnel were found to have a score indicating 'higher risk
      drinking'. Analysis of the qualitative data suggests that the EMHA is an easy
      tool to implement with minimal additional time and resources needed. The
      interviewees pointed out a number of limitations and suggestions for possible
      further studies. CONCLUSIONS: The pilot study successfully demonstrated that the
      EMHA questionnaire is easy to administer, does not take up a large amount of
      additional resources or manpower and provides a useful check of MH status. The
      study picked up an average number of MH cases and the questions on alcohol
      consumption highlighted that military personnel may be at a 'higher risk of
      drinking'.

PMID- 24109092
TI  - Alcohol consumption in the UK armed forces: are we drinking too much?

PMID- 24109093
TI  - Dental treatment on a German warship during a three-month deployment.
AB  - INTRODUCTION: Despite routine dental screenings and treatments before military
      deployments, dental emergencies may arise due to acute infections, trauma or
      failed restorations. The purpose of this study is to evaluate the dental service
      during a three-month deployment on a German warship. METHODS: A retrospective
      analysis of dental attendances and treatments in a German naval task group of
      three ships with an average total of 650 soldiers. Diagnosis, treatments
      performed, percentage of emergencies, routine procedures and numbers of
      appointments were recorded. RESULTS: Out of 650 soldiers, there were 71 patients
      (10.92%) with a mean age of 25.1 +/-5 .3 years. Out of 136 treatments, 17.65%
      were for emergency treatment, which is equivalent to 3.69% of all servicemen of
      the task group. Combining the reasons for dental emergencies, 95.84% were caused
      by caries. CONCLUSIONS: The pre-screening of sailors before an overseas
      deployment is necessary to avoid severe dental treatments. Caries remains the
      main cause for dental emergencies, and medical doctors should be trained to treat
      caries lesions if a dentist is not on board.

PMID- 24109094
TI  - A survey of post-amputation pains in serving military personnel.
AB  - INTRODUCTION: Amputation is a common injury in survivors of current military
      conflicts. The primary aim of this study was to establish the prevalence rate of
      phantom limb pain (PLP) in military personnel undergoing rehabilitation at the
      UK's Defence Medical Rehabilitation Centre. The secondary aims were to establish
      treatment failure rates and prevalence rates of phantom limb sensations (PLS) and
      residual limb pains (RLP). METHOD: A questionnaire survey was developed from that
      used in a previous study of pains in veterans. Questions were asked of the
      intensity of PLP, RLP and PLS over the previous month and the entire time since
      amputation. Treatment failure was defined as greater than 'mild' pain. A
      literature review for similar studies was undertaken. RESULTS: There were 48
      responders with 65 amputations. PLP in the previous month was reported by 49% of
      respondents and 20% were classed as treatment failures; 76% had PLP at some point
      and 56% were analgesic failures. PLS was commoner with 70% reported over the
      previous month and 66% at any time. 65% had RLP over the previous month, 31% were
      treatment failures and 80% had experienced RLP at some point and 63% of these
      were failures of treatment. Eight other papers were found for comparison.
      CONCLUSIONS: This is the first paper that describes prevalence of pains
      associated with amputation in a serving military population. It also describes
      the use of analgesic failure as a concept and provides an encouraging rate of as
      low as 20% in this population.

PMID- 24109095
TI  - Determining the velocity required for skin perforation by fragment simulating
      projectiles: a systematic review.
AB  - INTRODUCTION: Explosively propelled fragments are the most common cause of injury
      to soldiers on current operations. Researchers desire models to predict their
      injurious effects so as to refine methods of potential protection. Well validated
      physical and numerical models based on the penetration of standardised fragment
      simulating projectiles (FSPs) through muscle exist but not for skin, thereby
      reducing the utility of such models. METHOD: A systematic review of the
      literature was undertaken using the Preferred Reporting Items for Systematic
      Reviews and Meta-Analyses methodology to identify all open source information
      quantifying the effects of postmortem human subject (PMHS) and animal skin on the
      retardation of metallic projectiles. Projectile sectional density (mass over
      presented cross-sectional area) was compared with the velocity required for skin
      perforation or penetration, with regard to skin origin (animal vs PMHS),
      projectile shape (sphere vs cylinder) and skin backing (isolated skin vs that
      backed by muscle). RESULTS: 17 original experimental studies were identified,
      predominantly using skin from the thigh. No statistical difference in the
      velocity required for skin perforation with regard to skin origin or projectile
      shape was found. A greater velocity was required to perforate intact skin on a
      whole limb than isolated skin alone (p<0.05). An empirical relationship
      describing the velocity required to perforate skin by metallic FSPs of a range of
      sectional densities was generated. DISCUSSION: Skin has a significant effect on
      the retardation of FSPs, necessitating its incorporation in future injury models.
      Perforation algorithms based on animal and PMHS skin can be used interchangeably
      as well as spheres and cylinders of matching sectional density. Future numerical
      simulations for skin perforation must match the velocity for penetration and also
      require experimental determination of mechanical skin properties, such as tensile
      strength, strain and elasticity at high strain rates.

PMID- 24109096
TI  - Gunshot induced indirect femoral fracture: mechanism of injury and fracture
      morphology.
AB  - INTRODUCTION: Indirect ballistic fractures occur when a projectile passes close
      to, but not contacting, the bone. The mechanism of how these fractures occur is
      not yet proven, but recently the acoustic shockwave has been excluded as a cause.
      The objective of this study is to determine whether the expanding temporary
      cavity, the collapse of this cavity or its oscillation causes these fractures. In
      addition, we describe the fracture morphology and biomechanical causes of this
      injury. METHOD: 40 fresh deer femora were strain gauged and embedded in ballistic
      gelatin before being shot with four different projectiles with varying distances
      off the bone. Pressure recordings, chronographs and radar allowed assessment of
      local pressures and energy transfer. High-speed video allowed the temporal
      relationship between the temporary cavity and fracture formation to be analysed,
      while sample dissection allowed the fracture morphology to be described. RESULTS:
      The fractures produced were consistently wedge-shaped and caused by the expansion
      of the temporary cavity, flexing the bone beyond its yield point, causing tension
      failure on the cortex opposite the expanding temporary cavity and a compression
      wedge on the side of the cavity. Local pressure was not predictive of fracture
      formation but the energy transfer to the gelatin block was predictive.
      CONCLUSIONS: Indirect fractures are caused by the expansion of the temporary
      cavity and relate to the proximity of this cavity to the bone. Fractures occur
      from flexion of the bone and classically display wedge-shaped fracture patterns
      with the apex of the wedge pointing away from the expanding cavity.

PMID- 24109097
TI  - French military general practitioner: ultrasound practice.
AB  - OBJECTIVES: Ultrasound has been used in the field and in emergency departments
      for more than two decades. In a military setting, its use has grown rapidly as it
      has gained widespread acceptance among emergency physicians and as the range of
      diagnostic and triage applications has continued to expand. Technological changes
      have enabled ultrasound devices to become accessible to general practitioners
      (GP), and it could be of particular interest for military GPs in isolated
      environments. We have investigated both the training of French military GPs in
      the area of ultrasonography and the use of ultrasound devices, in daily practice
      and abroad, in isolated military settings. METHODS: In 2011, a questionnaire was
      sent to all 147 in-the-field GPs of the French southeast regional military health
      service. The questionnaire evaluated the training of military GPs in
      ultrasonography, the use of ultrasound in France in daily practice, and during
      military operations in isolated environments abroad during 2010. RESULTS: The
      response rate was 52%. On the one hand, half the responding GPs had been
      specially trained in ultrasound, mainly (97%) in military institutes. On the
      other hand, only a quarter of doctors used ultrasound in daily practice. Among
      those GPs performing ultrasound examinations in France, 75% used it in 2010
      during isolated operations abroad. Ultrasound examinations performed in such an
      austere environment were retrospectively declared useful to guide clinical
      reasoning (41% of examinations carried out), diagnosis (21%) and decision making
      as regards evacuation (11%). CONCLUSIONS: The challenge for the future is to make
      ultrasound courses mandatory for all military GPs going on overseas operations,
      to develop daily practice, and to investigate effective triage systems, combining
      both ultrasound imagery and physical examination.

PMID- 24109098
TI  - Femoral and tibial stress fractures associated with vitamin D insufficiency.
AB  - We describe a case highlighting the need to consider hypovitaminosis-D when
      investigating background causation and treatment of femoral and tibial stress
      fractures. The case also suggests that prescribing calcium and vitamin D
      supplementation may help with fracture healing in soldiers presenting with stress
      fractures who may have unrecognised hypovitaminosis-D which if left untreated may
      delay fracture healing. 

PMID- 24109099
TI  - Determining the wounding effects of ballistic projectiles to inform future injury
      models: a systematic review.
AB  - INTRODUCTION: Penetrating wounds from explosively propelled fragments and bullets
      are the most common causes of combat injury experienced by UK service personnel
      on current operations. There is a requirement for injury models capable of
      simulating such a threat in order to optimise body armour design. METHOD: A
      systematic review of the open literature was undertaken using the Preferred
      Reporting Items for Systematic Reviews and Meta-Analyses methodology. Original
      papers describing the injurious effects of projectiles on skin, bone, muscle,
      large vessels and nerves were identified. RESULTS: Projectiles injure these
      tissues by producing a permanent wound tract (PWT), comprised of a central
      permanent wound cavity, in conjunction with a zone of irreversible macroscopic
      tissue damage laterally. The primary mechanism of injury was the crushing and
      cutting effect of the presented surface of the projectile, with an additional
      smaller component due to macroscopic damage produced by the radial tissue
      displacement from the temporary tissue cavity (TTC). No conclusive evidence could
      be found for permanent pathological effects produced by the pressure wave or that
      any microscopic tissue changes due to the TTC (in the absence of visible
      macroscopic damage) led to permanent injury. DISCUSSION: Injury models should use
      the PWT to delineate the area of damage to tissues from penetrating ballistic
      projectiles. The PWT, or its individual components, will require quantification
      in terms of the amount of damage produced by different projectiles penetrating
      these tissues. There is a lack of information qualifying the injurious effect of
      the temporary cavity, particularly in relation to that caused by explosive
      fragments, and future models should introduce modularity to potentially enable
      incorporation of these mechanisms at a later date were they found to be
      significant.

PMID- 24109100
TI  - One year of burns at a role 3 Medical Treatment Facility in Afghanistan.
AB  - OBJECTIVES: Historically, burns have formed a significant proportion of the
      casualties of war. The management of burns in recent conflict has been found to
      be a resource-heavy undertaking, though its impact on both personnel and
      resources in current conflicts is unclear. A case analysis has been carried out
      in order to quantify the logistical impact of the management of burns on Role 3
      Medical Treatment Facility (MTF) infrastructure and to examine if and how the
      cause and management of burns have evolved in early 21st century conflict.
      METHODS: All casualties treated for burns at a Role 3 MTF over one calendar year
      were identified and scanned copies of their notes obtained from the UK Joint
      Theatre Trauma Registry and retrospectively analysed. RESULTS: 88 of the 1461
      (6.0%) trauma patients presenting to the Role 3 MTF over the year were treated
      for burns of whom 52.3% were combat troops and 45.4% civilians. Half of the burns
      were caused by non-conflict related mechanisms; the two commonest mechanisms were
      flame burns in 38/88 mostly non-conflict related cases and blast in 30/88 cases
      most of which were conflict related. CONCLUSIONS: The management of burns at war
      is a complex process. It is further confounded by the management of civilians
      with non-conflict related burns, which places a predictable strain on Role 3 MTF
      resources: theatre time, nursing time, dressing resources and bed space. This
      must be planned for in current and future deployed operations.

PMID- 24109102
TI  - Ergonomic assessment of enhanced protection under body armour combat shirt neck
      collars.
AB  - INTRODUCTION: Combat neck injury due to explosively propelled fragments is a
      significant cause of mortality and long-term morbidity in UK soldiers deployed on
      current operations. Reinforcing the collar of the existing under body armour
      combat shirt (UBACS) has been suggested as a potential method for reducing the
      incidence of combat neck injury. METHOD: 20 soldiers serving in Afghanistan
      objectively compared three designs of enhanced protection UBACS (EP-UBACS) using
      10 representative military tasks against a baseline of a standard UBACS. Each EP
      UBACS design was trialled using three constituent materials: two layers of para
      aramid felt, one layer of ultra high molecule weight polyethylene (UHMWPE) felt
      or two layers of a silk fabric. Subjective assessment of these nine
      configurations in terms of comfort, heat dissipation and overall acceptability
      were compared with the standard UBACS using a chi2 test. RESULTS: All military
      tasks could be performed with all nine configurations of EP-UBACS. Although silk
      was the most comfortable material, it was not functionally practical in any of
      the three designs. Crossover collars incorporating UHMWPE or para-aramid were the
      only two of the nine configurations to demonstrate similar user acceptability to
      a standard UBACS. CONCLUSIONS: The EP-UBACS has the potential to provide neck
      protection without reducing performance incorporating materials analogous to
      either of the felts assessed in this study. The collar should provide stand-off
      from the skin to improve heat dissipation and comfort, which can be maximised by
      changing the current UBACS collar shape to one that crosses over at the front.
      Should a zip be desired, it should be moved to one side of the midline to reduce
      rubbing on the chin and be covered with ballistic protective material. Additional
      semi-circles of silk beneath the collar at the front and back would improve
      protection without affecting comfort.

PMID- 24109103
TI  - The changing pattern of amputations.
AB  - INTRODUCTION: Conflict in the Middle East over the past 10 years has seen a
      change in warfare tactics from the use of ballistic missiles to blast weapons,
      which has resulted in a well-documented change in wounding patterns. Due to the
      severity of these injuries, there have been large numbers of amputations, both as
      life and limb saving procedures. The purpose of this paper is to retrospectively
      review all UK service personnel who have undergone limb amputation in the last 8
      years of conflict and compare those from the early years with the more recent.
      METHODS: All UK service personnel scoring more than 1 on the extremity score of
      the Abbreviated Injury Score were identified from the UK Joint Theatre Trauma
      Registry and separated into two temporal cohorts (August 2003-February 2008 and
      August 2008-July 2010). Intheatre medical facility and Role 4 hospital notes from
      the Queen Elizabeth Hospital Birmingham were examined for details of mechanisms
      of injury, number of limbs injured, associated injuries, method of amputation,
      microbiology of contaminating organisms and outcome. RESULTS: There were
      significant differences in the nature of the amputations, the number of multiple
      amputations and soft tissue perineal wounds, as well as a significantly higher
      Injury Severity Score in the later time period. There were also significant
      differences in the surgical techniques, with more guillotine amputations in the
      early group, and mechanism of injury, with more blast injuries in the late group.
      CONCLUSIONS: This study has confirmed the clinical impression that there has been
      a significant change in the limb trauma from the Iraq conflict to Afghanistan.
      These injury patterns have significantly different logistic implications and this
      must be considered when planning the required medical assets in future conflicts.

PMID- 24109104
TI  - Response to: the safety and efficacy, and recommendations for the use of biologic
      drugs in the UK military rheumatology population.

PMID- 24109105
TI  - Defining combat helmet coverage for protection against explosively propelled
      fragments.
AB  - INTRODUCTION: Prevention against head wounds from explosively propelled fragments
      is currently the Mark 7 general service combat helmet, although only limited
      evidence exists to define the coverage required for the helmet to adequately
      protect against such a threat. The Royal Centre for Defence Medicine was tasked
      by Defence Equipment and Support to provide a framework for determining the
      optimum coverage of future combat helmets in order to inform the VIRTUS
      procurement programme. METHOD: A systematic review of the literature was
      undertaken to identify potential solutions to three components felt necessary to
      define the ideal helmet coverage required for protection against explosively
      propelled fragments. RESULTS: The brain and brainstem were identified as the
      structures requiring coverage by a helmet. No papers were identified that
      directly defined the margins of these structures to anatomical landmarks, nor how
      these could be related to helmet coverage. CONCLUSIONS: We recommend relating the
      margins of the brain to three identifiable anatomical landmarks (nasion, external
      auditory meatus and superior nuchal line), which can in turn be related to the
      coverage provided by the helmet. Early assessments using an anatomical mannequin
      indicate that the current helmet covers the majority of the brain and brainstem
      from projectiles with a horizontal trajectory but not from ones that originate
      from the ground. Protection from projectiles with ground-originating trajectories
      is reduced by helmets with increased stand-off from the skin. Future helmet
      coverage assessments should use a finite element numerical modelling approach
      with representative material properties assigned to intracranial anatomical
      structures to enable differences in projectile trajectory and helmet coverage to
      be objectively compared.

PMID- 24109106
TI  - The challenges in developing a finite element injury model of the neck to predict
      the penetration of explosively propelled projectiles.
AB  - INTRODUCTION: Neck injuries sustained by UK service personnel serving on current
      operations from explosively propelled fragments result in significant mortality
      and long-term morbidity. Many of these injuries could potentially have been
      prevented had the soldiers been wearing their issued neck collars at the time of
      injury. The aim of this research is to develop an accurate method of predicting
      the resultant damage to cervical neurovascular structures from explosively
      propelled fragments. CURRENT STATUS: A finite element numerical model has been
      developed based on an anatomically accurate, anthropometrically representative 3D
      mathematical mesh of cervical neurovascular structures. Currently, the model
      simulates the passage of a fragment simulating projectile through all anatomical
      components of the neck using material models based upon 20% ballistic gelatin on
      the simplification that all tissue types act like homogenous muscle. FUTURE
      RESEARCH: The material models used to define the properties of each element
      within the model will be sequentially replaced by ones specific to each
      individual tissue within an anatomical structure. However, the cumulative effect
      of so many additional variables will necessitate experimental validation against
      both animal models and post-mortem human subjects to improve the credibility of
      any predictions made by the model. We believe this approach will in the future
      have the potential to enable objective comparisons between the mitigative effects
      of different body armour systems to be made with resultant time and financial
      savings.

PMID- 24109107
TI  - Challenges of managing toxic alcohol poisoning in a resource-limited setting.
AB  - We present a series of patients with profound metabolic acidosis admitted to the
      Role 3 Medical Treatment Facility, Camp Bastion, Afghanistan, in 2012. A police
      service breath alcohol analyser, calculation of the osmolar gap and urine
      microscopy assisted in diagnosing methanol poisoning. The challenge of diagnosing
      and managing toxic alcohol poisoning in this resource-limited setting is
      discussed. We believe this is the first description of using a breath alcohol
      analyser to assist a diagnosis of methanol poisoning. 

PMID- 24109109
TI  - The effectiveness of blood product warming circuits in a simulated MERT
      environment.

PMID- 24109110
TI  - Successful management of a severe combat penetrating brain injury.
AB  - We report the case of successful management of a transcranial penetrating high
      energy transfer injury in a 20-year-old soldier. The bullet traversed both
      cerebral hemispheres and lacerated the superior sagittal sinus rendering him
      unconscious. We detail the care received at all stages following injury from
      'Buddy Aid' on the battlefield, resuscitation by a forward medical team through
      to prompt neurosurgery within 2 h of injury. Subsequent aeromedical evacuation
      and continuing aggressive critical care has allowed the patient to survive with
      acceptable neurological impairment after what is generally considered an
      unsurvivable injury.

PMID- 24109111
TI  - Misdiagnosis of cutaneous leishmaniasis and recurrence after surgical excision.
AB  - Cutaneous Leishmaniasis (CL) occurs in British troops deployed to Belize,
      Afghanistan, Iraq and elsewhere. From 1998 to 2009, 156 (45%) of 343 confirmed
      cases seen in the UK were in military personnel. CL is a rare disease and
      requires specialist clinical management because numerous pitfalls exist during
      diagnosis and treatment. A 19-year-old soldier developed CL on his neck 6 weeks
      after taking part in jungle warfare training in Belize. However, this was not
      suspected and the diagnosis was not made from either a skin biopsy or following
      surgical excision. The travel history and the patient's own photograph prompted
      retrospective investigations that confirmed this was CL due to Leishmania
      mexicana. Three months after surgery, the disease recurred locally and was
      treated appropriately with a good outcome. British military personnel with
      suspected CL should be referred to the UK Role 4 Military Infectious Diseases &
      Tropical Medicine Service. 

PMID- 24109112
TI  - Evaluation of a disposable sheath bronchoscope system for use in the deployed
      field hospital.
AB  - At present, UK field hospitals use standard flexible bronchoscopes which require
      specialised disinfection services that are not integral to the hospital. This
      leads to prolonged turnover of used bronchoscopes as they have to be sent away to
      external facilities, which takes 1-3 days and is dependent on air transport to
      other facilities. In contingency operations, off site sterilisation facilities
      may not be available. There is a need for a bronchoscope system which can be
      rapidly cleaned and reused. We evaluated the Vision Sciences EndoSheath
      Bronchoscopy system, which uses a disposable outer sheath to remove the need for
      specialised disinfection. We report our experience of using this system in a
      deployed field hospital in Afghanistan.

PMID- 24109113
TI  - The Role 1 capability review: mitigation and innovation for Op HERRICK 18 and
      into contingency.
AB  - The Role 1 orientated JRAMC of September 2012 was a welcome addition to the body
      of Role 1 literature. In particular, the Role 1 capability review by Hodgetts and
      Findlay detailed both current issues and future aspirations for Role 1 provision.
      This personal view considers issues still prevalent during Op HERRICK 18 namely
      the provision of primary healthcare by combat medical technicians on operations
      and the organisational issues that contribute to historical structural and
      attitudinal obstructions to the employment of combat medical technicians in firm
      base primary healthcare. It also considers a dynamically updating dashboard
      capable of displaying risk across the Role 1 network with the implied move to a
      model of continuous healthcare assurance. 

PMID- 24109114
TI  - A modern combat trauma.
AB  - INTRODUCTION: The world remains plagued by wars and terrorist attacks, and
      improvised explosive devices (IED) are the main weapons of our current enemies,
      causing almost two-thirds of all combat injuries. We wished to analyse the
      pattern of blast trauma on the modern battlefield and to compare it with combat
      gunshot injuries. MATERIALS AND METHODS: Analysis of a consecutive series of
      combat trauma patients presenting to two Bulgarian combat surgical teams in
      Afghanistan over 11 months. Demographics, injury patterns and Injury Severity
      Scores (ISS) were compared between blast and gunshot-injured casualties using
      Fisher's Exact Test. RESULTS: The blast victims had significantly higher median
      ISS (20.54 vs 9.23) and higher proportion of ISS>16 (60% vs 33.92%, p=0.008) than
      gunshot cases. They also had more frequent involvement of three or more body
      regions (47.22% vs 3.58%, p<0.0001). A significantly higher frequency of head
      (27.27% vs 3.57%), facial (20% vs 0%) and extremities injuries (85.45% vs 42.86%)
      and burns (12.72% vs 0%) was noted among the victims of explosion (p<0.0001).
      Based on clinical examination and diagnostic imaging, primary blast injury was
      identified in 24/55 (43.6%), secondary blast injury in 37 blast cases (67.3%),
      tertiary in 15 (27.3%) and quaternary blast injury (all burns) in seven (12.72%).
      CONCLUSIONS: Our results corroborate the 'multidimensional' injury pattern of
      blast trauma. The complexity of the blast trauma demands a good knowledge and a
      special training of the military surgeons and hospital personnel before
      deployment.

PMID- 24109116
TI  - The medical aspects of the 1565 Great Siege of Malta.
AB  - The 1565 Siege of Malta served as a turning point in the westward Ottoman
      advance. The 4-month long siege was resisted by the indomitable belief of the
      defenders that their cause was just and holy. It also required prior detailed
      organisation to ensure sufficient war materials and that the overall health of
      the combatants and non-combatants was maintained throughout the months of the
      siege. This article reviews the contemporary and historical sources relating to
      the conflict to identify the medical operational plans used by the military
      during this historic siege. 

PMID- 24109117
TI  - Know pain know gain: proposing a treatment approach for phantom limb pain.
AB  - Phantom limb pain affects between 50 and 80% of amputees. With an increasing
      number of battle casualties having had an amputation after combat trauma, it is
      inevitable that both primary and secondary care clinicians will come into contact
      with a patient with phantom limb pain (PLP). It is widely acknowledged that its
      complex aetiology means that this condition is often poorly understood and
      difficult to manage. A growing pathophysiological understanding is shedding new
      light on the mechanisms which underlie PLP. Knowledge of these mechanisms will
      inform treatment and enable clinicians to plan and implement solutions which make
      a difference to those individuals with this condition. This paper seeks to
      outline current research into this condition and proposes an approach to
      treatment. This approach has been formulated from an amalgamation of clinical
      experience working with battle casualties at the Defence Medical Rehabilitation
      Centre, Headley Court. 

PMID- 24109118
TI  - Sir Gilbert Blane: the father of naval medical science.

PMID- 24109119
TI  - Treatment of rectal war wounds.
AB  - Treatment strategies for penetrating rectal injuries (PRI) in civilian settings
      are still not uniformly agreed, in part since high-energy transfer PRI, such as
      is frequently seen in military settings, are not taken into account. Here, we
      describe three cases of PRI, treated in a deployed combat environment, and
      outline the management strategies successfully employed. We also discuss the
      literature regarding PRI management. Where there is a major soft tissue
      component, repetitive debridement and vacuum therapy is useful. A loop or end
      colostomy should be used, depending on the degree of damage to the anal sphincter
      complex. 

PMID- 24109120
TI  - The damage control surgery set: rethinking for contingency.

PMID- 24109122
TI  - Did the Olympics need more drugs? a doctor's reflection on providing medical care
      during Op OLYMPICS.
AB  - This paper examines some of the medical problems arising from the successful
      deployment of Defence Medical Services personnel to Op OLYMPICS (mid-June 2012
      September 2012). It does not aim to be all encompassing in its scope, but focuses
      on the most pressing issues affecting a junior military doctor's ability to work
      effectively under field conditions. This will entail a discussion about whether
      in a deployment such as Op OLYMPICS medical care should be based upon offering
      solely primary healthcare in medical centres or using Role 1 medical treatment
      facilities, which include primary healthcare and pre-hospital emergency care. The
      main recommendations arising from the deployment are: clinicians should deploy
      with a minimum of basic emergency drugs and equipment; a medical facility
      treating a large population at risk for a prolonged period should have a broad
      stock of medications available on site; and medical risk assessments must be
      performed on all Reservists during mobilisation. 

PMID- 24109125
TI  - A high quality library service.

PMID- 24109131
TI  - Disease and non-battle injury(DNBI) have always caused much greater morbidity.

PMID- 24109132
TI  - Update on military diarrhoea: current status and future plans.

PMID- 24109133
TI  - UK role 4 military infection services: past, present and future.
AB  - NATO describes 'Role 4' military medical services as those provided for the
      definitive care of patients who cannot be treated within a theatre of operations
      and these are usually located in a military force's country of origin and may
      include the involvement of civilian medical services. The UK Defence Medical
      Services have a proud history of developing and providing clinical services in
      infectious diseases and tropical medicine, sexual health and HIV medicine, and
      medical microbiology and virology. These UK Role 4 Military Infection Services
      have adapted well to recent overseas deployments, but new challenges will arise
      due to current military cutbacks and a greater diversity of contingency
      operations in the future. Further evidence-based development of these services
      will require leadership by military clinicians and improved communication and
      support for 'reach-back' services. 

PMID- 24109134
TI  - Rapid intelligence and failing weapons: meeting the challenges of 21st century
      infections in the deployed clinical environment.

PMID- 24109135
TI  - A brief history of British military experiences with infectious and tropical
      diseases.
AB  - Infectious and tropical diseases have been a problem for British expeditionary
      forces ever since the Crusades. Outbreaks were especially common on Navy ships
      from the 16th to 18th centuries due to poor living conditions and travel to the
      tropics. However, since these occurred in small, isolated and controlled
      environments it meant that naval medical practitioners were able to keep detailed
      records and develop empirical approaches for their prevention. The first Royal
      Naval Hospitals were established in response to these diseases and Royal Navy
      doctors made valuable early contributions towards understanding them. Even larger
      outbreaks of infectious and tropical diseases occurred in the Army during the
      Napoleonic, Crimean and Boer Wars and throughout the colonial era, which strongly
      influenced the formation of the Army Medical Services including provision for
      teaching and research. The establishment of germ theory led to a golden era of
      discovery regarding these diseases and British Army doctors made numerous
      important contributions. Subsequent improvements in prevention, diagnosis and
      treatment reduced the mortality from infectious and tropical diseases during the
      World Wars, but they remained a significant problem in the non-European campaigns
      and also the numerous 'small wars' that followed. Even in the 21st century some
      of these diseases still cause outbreaks with significant morbidity and impact on
      deployments, but the military clinical and academic resources to deal with them
      are now much reduced. Preventive measures such as hygiene, sanitation, infection
      control, vaccination and chemoprophylaxis are invaluable, but history shows that
      these can become neglected over time and disrupted or overwhelmed during the
      early or most intense stages of military operations. This is why military
      specialists in infectious diseases, tropical medicine, sexual health, medical
      microbiology and communicable diseases control are still required. 

PMID- 24109136
TI  - Malaria.
AB  - Malaria is a life-threatening disease, with its largest impact being due to
      Plasmodium falciparum infection in Africa. Military populations continue to be at
      a high risk of malaria and reported case series have frequently revealed poor
      compliance with preventative measures. The symptoms of malaria are non-specific
      and its management depends on awareness of the diagnosis and early recognition
      and treatment. This is aided by new and simple rapid diagnostic tests, but these
      should not replace the examination of blood films if these are available.
      Artemisinin combination therapy provides a more rapid and dependable cure of
      uncomplicated P falciparum infection, with artesunate now being the drug of
      choice in severe infection. 

PMID- 24109137
TI  - Hepatitis E: the forgotten virus.
AB  - Hepatitis E virus (HEV) has a long military association being first discovered
      during the Soviet occupation of Afghanistan in the 1980s after an outbreak of
      unexplained hepatitis at a military camp. HEV is now endemic in the UK, and
      should be considered in all cases of jaundice. The prevalence is high in certain
      operational areas (28.5% in Afghanistan), and maintenance of integrity of food
      and water supplies together with scrupulous attention to environmental hygiene
      remains paramount. Pregnancy confers a much higher risk of fulminant hepatitis,
      with a mortality rate of up to 25%. Management is usually symptomatic, but
      ribavirin can be considered in non-pregnant patients with fulminant hepatitis.
      This narrative review examines the presentations and management of Hepatitis E in
      military populations. 

PMID- 24109138
TI  - Hepatitis B and C in the armed forces.
AB  - Hepatitis B and hepatitis C are prevalent in several areas of the world. Armed
      Forces personnel may be exposed to these viruses through risk behaviour or
      ballistic transmission. This article discusses the epidemiology and treatment of
      these viruses, together with occupational health considerations. 

PMID- 24109139
TI  - Sepsis management in the deployed field hospital.
AB  - Sepsis, a syndrome caused by severe infection, affects a small proportion of
      military casualties but has a significant effect in increasing morbidity and
      mortality, including causing some preventable deaths. Casualties with abdominal
      trauma and those with significant tissue loss appear to be at a greater risk of
      sepsis. In this article, the diagnosis and management of sepsis in military
      casualties with reference to the Surviving Sepsis Campaign guidelines are
      examined. We discuss the management considerations specific to military
      casualties in the deployed setting and also discuss factors affecting evacuation
      by the UK Royal Air Force Critical Care Air Support Team. 

PMID- 24109140
TI  - Respiratory infections in the military.
AB  - Military training facilities and operational theatres, and the stressful
      activities undertaken in such settings, are unique. Military personnel living and
      working in these environments are at considerable risk of the acquisition and
      onward transmission of a variety of respiratory infections. While these generally
      cause mild illness, severe disease may occur with significant associated
      morbidity and, occasionally, mortality. Epidemic outbreaks among military
      personnel may have a significant detrimental impact on training schedules and
      operational effectiveness. The recognition of the burden of such illness among
      British military personnel, and the development of strategies required to prevent
      or limit negative impacts, can only be achieved through the use of comprehensive
      laboratory-based surveillance programmes. 

PMID- 24109141
TI  - Tuberculosis and the military.
AB  - Tuberculosis (TB) causes significant morbidity and mortality among the global
      civilian population. Historically, TB has also been responsible for a
      considerable burden of disease among military populations during periods of both
      peace and conflict. TB will continue to be of importance to the military for
      several reasons. Military units live and work in confined environments, personnel
      may deploy to areas highly endemic for TB where there is the potential to be
      exposed to infected local communities, and they undertake physiologically
      stressful activities during training and operations. These are just a few of the
      factors that may increase the risk of acquiring, developing and transmitting TB
      among military personnel. This review examines the military relevance of TB in
      the modern era within the context of epidemiological, pathological and clinical
      considerations of this ancient disease. 

PMID- 24109142
TI  - Undifferentiated febrile illnesses in military personnel.
AB  - Undifferentiated febrile illnesses (UFIs) present with acute symptoms, objective
      fever and no specific organ focus on clinical assessment. The term is mostly used
      in developing and tropical countries where a wide range of infections may be
      responsible. Laboratory diagnosis often requires specialist microbiology
      investigations that are not widely available, and serology tests that only become
      positive during convalescence. Optimal clinical management requires a good travel
      history, awareness of local endemic diseases, an understanding of the features
      that may help distinguish different causes and appropriate use of empirical
      antibiotics. This review describes the most common examples of UFI in military
      personnel on overseas deployments, and provides a practical approach to their
      initial management. 

PMID- 24109143
TI  - Sexual health and HIV in the Army.
AB  - Sexual acquisition of infections has always been an important part of military
      history and although disease patterns have changed over time, the problem has not
      gone away. This article will look at how to recognise infection, the general
      principles of management, where to access guidance and how to get specialised
      help within the complexities of the military environment. 

PMID- 24109144
TI  - Skin and soft tissue infections in the military.
AB  - Skin and soft tissue infections (SSTI) are common in military populations
      regularly living and training in close contact with each other. The majority of
      such infections are simple and can be easily treated with antibiotics and
      appropriate infection control practices. Some, however, can progress to become
      complex and even life threatening, such as Panton-Valentine Leukocidin (PVL)
      associated staphylococcus aureus pneumonia, or Streptococcus pyogenes necrotising
      fasciitis, which carry a mortality rate of up to 65% and 30%, respectively. This
      review focuses on the most important SSTIs and those more commonly affecting
      military personnel with advice on how they are best managed. 

PMID- 24109145
TI  - Tropical skin diseases in British military personnel.
AB  - Skin complaints are common in travellers to foreign countries and are responsible
      for up to 25% of medical consultations by military personnel during deployments
      in the tropics. They also have relatively high rates of field hospital admission,
      medical evacuation and referral to UK Role 4 healthcare facilities. Non
      infectious tropical skin diseases include sunburn, heat rash, arthropod bites,
      venomous bites, contact dermatitis and phytophotodermatitis. During tropical
      deployments skin infections that commonly occur in military personnel may become
      more frequent, severe and difficult to treat. Several systemic tropical
      infections have cutaneous features that can be useful in making early diagnoses.
      Tropical skin infections such as cutaneous larva migrans, cutaneous myiasis,
      cutaneous leishmaniasis and leprosy do occur in British troops and require
      specialist clinical management. This illustrated review focuses on the most
      significant tropical skin diseases that have occurred in British military
      personnel in recent years. Clinical management of these conditions on deployments
      would be improved and medical evacuations could be reduced if a military
      dermatology 'reach-back' service (including a telemedicine facility) was
      available. 

PMID- 24109146
TI  - Deployed antimicrobial stewardship: an audit of antimicrobial use at Role 3.
AB  - INTRODUCTION: Infections due to multidrug-resistant organisms are increasingly
      prevalent, and antimicrobial stewardship has become a priority for many
      healthcare organisations, including the Defence Medical Services. In military
      environments, infectious diseases remain a significant burden, and infections
      complicating the care of modern complex combat injuries are well recognised. A
      focus on infection prevention and control in the deployed environment is
      essential, and an important element of this is an antimicrobial formulary and
      stewardship programme. This audit analyses antimicrobial prescribing practices by
      military clinicians in patients admitted to UK/US Role 3 medical treatment
      facility in Camp Bastion, Afghanistan, relative to the UK published guidance.
      METHODS: Retrospective case note review of all in-patient admissions during two
      time periods (October 2011 and October 2012). Notes were independently reviewed
      by an infection specialist not involved in the management of the patients.
      RESULTS: 475 case notes were reviewed, of which 250 received antimicrobials.
      Coalition forces represented the most common patient group (131/250), with battle
      injury the most frequent indication (139/250) for antimicrobial prescription,
      followed by disease (100/250). A total of 302 antimicrobials were prescribed,
      with co-amoxiclav being the most frequently used antibiotic in 74% (185/250) of
      patients. 84.8% (212/250) were prescribed antimicrobials in line with the
      antimicrobial formulary. In battle injury, 93.5% (130/139) of antimicrobial
      prescriptions were in line with the formulary compared with 73.9% (82/111) in
      disease and non-battle injury patients. CONCLUSIONS: Maintaining a strong
      infection control effort in the deployed setting, even in a stabilised
      operational environment, is difficult, but our data show good compliance to the
      antimicrobial formulary superior to that reported in civilian hospitals. To
      improve this, further innovative strategies are required, combined with a
      continued focus on infection control basics across the full spectrum of care.

PMID- 24109147
TI  - Metabolic rate and body size are linked with perception of temporal information.
AB  - Body size and metabolic rate both fundamentally constrain how species interact
      with their environment, and hence ultimately affect their niche. While many
      mechanisms leading to these constraints have been explored, their effects on the
      resolution at which temporal information is perceived have been largely
      overlooked. The visual system acts as a gateway to the dynamic environment and
      the relative resolution at which organisms are able to acquire and process visual
      information is likely to restrict their ability to interact with events around
      them. As both smaller size and higher metabolic rates should facilitate rapid
      behavioural responses, we hypothesized that these traits would favour perception
      of temporal change over finer timescales. Using critical flicker fusion
      frequency, the lowest frequency of flashing at which a flickering light source is
      perceived as constant, as a measure of the maximum rate of temporal information
      processing in the visual system, we carried out a phylogenetic comparative
      analysis of a wide range of vertebrates that supported this hypothesis. Our
      results have implications for the evolution of signalling systems and predator
      prey interactions, and, combined with the strong influence that both body mass
      and metabolism have on a species' ecological niche, suggest that time perception
      may constitute an important and overlooked dimension of niche differentiation.

PMID- 24109148
TI  - Ambient temperature influences birds' decisions to eat toxic prey.
AB  - Aposematic prey warn predators of their toxicity using conspicuous signals.
      However, predators regularly include aposematic prey in their diets, particularly
      when they are in a poor energetic state and in need of nutrients. We investigated
      whether or not an environmental factor, ambient temperature, could change the
      energetic state of predators and lead to an increased intake of prey that they
      know to contain toxins. We found that European starlings, Sturnus vulgaris,
      increased their consumption of mealworm, Tenebrio molitor, prey containing
      quinine (a mild toxin) when the ambient temperature was reduced below their
      thermoneutral zone from 20  degrees C to 6  degrees C. The birds differed in
      their sensitivity to changes in ambient temperature, with heavier birds
      increasing the number of toxic prey they ate more rapidly with decreasing
      temperature compared to birds with lower body mass. This could have been the
      result of their requiring more nutrients at lower temperatures or being better
      able to detoxify quinine. Taken together, our results suggest that conspicuous
      coloration may be more costly at lower temperatures, and that aposematic prey may
      need to invest more in chemical defences as temperatures decline. Our study also
      provides novel insights into what factors affect birds' decisions to eat toxic
      prey, and demonstrates that selection pressures acting on prey defences can vary
      with changing temperature across days, seasons, climes, and potentially in
      response to climate change.

PMID- 24109149
TI  - The benefit of evolving a larger brain: big-brained guppies perform better in a
      cognitive task.
AB  - *We previously selected for large and small brain size in guppies.*Large-brained
      females outperformed small-brained females in a learning task.*Healy and Rowe
      challenged our interpretations of larger brains = better learning.*Here we argue
      why we think they are mistaken.

PMID- 24109150
TI  - Do Parents Know Best? Examining the Relationship Between Parenting Profiles,
      Prevention Efforts, and Peak Drinking in College Students.
AB  - The study examined parent profiles among high school athletes transitioning to
      college and their association with high-risk drinking in a multi-site, randomized
      trial. Students (n = 587) were randomized to a control or combined parent-based
      and brief motivational intervention condition and completed measures at baseline
      and at 5- and 10-month follow-ups. Four parent profiles (authoritative,
      authoritarian, permissive, indifferent) were observed among participants.
      Findings indicated control participants with authoritarian parenting were at the
      greatest risk for heavy drinking. Alternately, students exposed to permissive or
      authoritarian parenting reported lower peak drinking when administered the
      combined intervention, compared to controls. Findings suggest the combined
      intervention was efficacious in reducing peak alcohol consumption among high-risk
      students based on athlete status and parenting profiles.

PMID- 24109151
TI  - Development and Validation of the Middle Years Development Instrument (MDI):
      Assessing Children's Well-Being and Assets across Multiple Contexts.
AB  - Few instruments provide reliable and valid data on child well-being and
      contextual assets during middle childhood, using children as informants. The
      authors developed a population-level, self-report measure of school-aged
      children's well-being and assets-the Middle Years Development Instrument (MDI)
      and examined its reliability and validity. The MDI was designed to assess child
      well-being inside and outside of school on five dimensions: (1) Social and
      emotional development, (2) Connectedness to peers and to adults at school, at
      home, and in the neighborhood, (3) School experiences, (4) Physical health and
      well-being, and (5) Constructive use of time after school. This paper describes
      the theoretical framework, selection of items and scales for the survey, and four
      studies that were conducted to revise the MDI and examine its psychometric
      properties. The findings indicate a theoretically predicted factor structure,
      high internal consistency, and document the convergent and discriminant validity
      of the MDI scales. The discussion delineates a plan for future validation studies
      that address further validity questions, such as predictive validity, measurement
      invariance, and fairness/bias, and provides a brief outlook of how the MDI may be
      used by practitioners, educators, and decision makers in schools and communities
      to motivate and inform action in support children's well-being.

PMID- 24109152
TI  - Medical informatics education at medical faculty of sarajevo university - 15
      years experience.
AB  - CONFLICT OF INTEREST: NONE DECLARED In Bosnia and Herzegovina, Medical
      informatics has been a separate subject for the last 15 years with regard to
      Medical curriculum at the biomedical faculties in the country (1,2). Education in
      the field of Medical informatics is based on the concept which is used in
      developed countries, according to the recommendations of the working groups EDU -
      Education of Medical Informatics, of the European Federation for Medical
      Informatics (EFMI) and International Medical Informatics Association (IMIA).
      Theoretical and practical teaching and training performance as a whole is
      performed by use of the computer equipment, and the final knowledge check of the
      students is also performed using the Data Base Management System MS Access
      specifically designed to cover full teaching and training material by using
      question sets in the data base which encircled nearly 1500 question combinations.
      The distance learning is logical step that can further improve this method of
      education. In this paper, authors present 15 years of experience of Medical
      informatics education at biomedical faculties in Bosnia and Herzegovina. Medical
      Informatics, as an obligatory subject, was introduced to the biomedical faculties
      in Sarajevo (medical, dental and pharmaceutical as well as the High medical
      school) in 1992 and 1993. Students have practical computer exercises for a period
      of 7 weeks. Students had training in Excel, Word etc. During the semester, the
      students perform specific operation such as creation of data carrier for
      manipulation with medical information. The information was analyzed by
      statistical program such as Excel. From 2002 years Medical Informatics is divided
      in two parts in order to facilitate data processing and other procedure that are
      necessary to perform at time when student's knowledge of medicine is sufficient
      for practicing specific tasks that include management the data about patient,
      anamnesis and similar parameters cause we noticed that students without such
      knowledge cannot figure out the whole picture without difficulties. The
      Theoretical part of examination is done using the multiple choice answer form
      provided by special software with randomly selected questions for each student.
      Such way of practical and theoretical path of final exam make possible to perform
      such procedures such as electronic registration for exam and distance testing.
      Possibilities of introduction of distance learning in medical curriculum are the
      title of project which has been realizing at Cathedra for medical Informatics,
      Medical faculty since year 2002. Our undergraduate and postgraduate students are
      satisfied with contents and organization of the teaching process.

PMID- 24109153
TI  - Cervical pain syndrome as consequence of computer use in daily practice.
AB  - CONFLICT OF INTEREST: NONE DECLARED NECK PAIN SYNDROME IS DESCRIBED AS: Pain in
      the neck affects at least once in a lifetime every second person, and also 10 %
      of adult population suffers from chronic pain in this area. It is more often
      among women. A constant increase of incidence in the industrialized countries is
      noticed. It is also the leading cause of referral to physical rehabilitation. It
      is causing huge financial costs in the health care system. There is no consensus
      regarding Neck pain syndrome management, but many therapeutic modalities are
      applied: a) to isolate (or manage) rare, but potentially dangerous states that
      can cause neck pain; b) identify and treat each co morbid state and risk factors;
      c) provide resources and information's, especially about regarding use computers
      in dayly practice. Physical and manual treatments can be: a) physical therapy can
      assist to achieve early mobilization and return to daily activities; b) active
      physical therapy , mobilization, manipulation and exercises can assure short time
      relief of neck pain; c) home based exercises, as shown by this research, can
      significantly prolong the pain free period, in case of patients with the chronic
      syndrome; d) Medications, combined with the exercise program and ergonomic
      improvements can be effective solution for the chronic or recurrent neck pain.
      Intensive treatments in Neck pain syndrome are: a) Surgical and other intensive
      treatment (rarely indicated); b) invasive treatments includes and percutaneous
      radiofrequent neurotomy and cervical epidural analgesis.

PMID- 24109154
TI  - E-learning as new method of medical education.
AB  - CONFLICT OF INTEREST: NONE DECLARED Distance learning refers to use of
      technologies based on health care delivered on distance and covers areas such as
      electronic health, tele-health (e-health), telematics, telemedicine, tele
      education, etc. For the need of e-health, telemedicine, tele-education and
      distance learning there are various technologies and communication systems from
      standard telephone lines to the system of transmission digitalized signals with
      modem, optical fiber, satellite links, wireless technologies, etc. Tele-education
      represents health education on distance, using Information Communication
      Technologies (ICT), as well as continuous education of a health system
      beneficiaries and use of electronic libraries, data bases or electronic data with
      data bases of knowledge. Distance learning (E-learning) as a part of tele
      education has gained popularity in the past decade; however, its use is highly
      variable among medical schools and appears to be more common in basic medical
      science courses than in clinical education. Distance learning does not preclude
      traditional learning processes; frequently it is used in conjunction with in
      person classroom or professional training procedures and practices. Tele
      education has mostly been used in biomedical education as a blended learning
      method, which combines tele-education technology with traditional instructor-led
      training, where, for example, a lecture or demonstration is supplemented by an
      online tutorial. Distance learning is used for self-education, tests, services
      and for examinations in medicine i.e. in terms of self-education and individual
      examination services. The possibility of working in the exercise mode with image
      files and questions is an attractive way of self education. Automated tracking
      and reporting of learners' activities lessen faculty administrative burden.
      Moreover, e-learning can be designed to include outcomes assessment to determine
      whether learning has occurred. This review article evaluates the current status
      and level of tele-education development in Bosnia and Herzegovina outlining its
      components, faculty development needs for implementation and the possibility of
      its integration as official learning standard in biomedical curricula in Bosnia
      and Herzegovina. Tele-education refers to the use of information and
      communication technologies (ICT) to enhance knowledge and performance. Tele
      education in biomedical education is widely accepted in the medical education
      community where it is mostly integrated into biomedical curricula forming part of
      a blended learning strategy. There are many biomedical digital repositories of e
      learning materials worldwide, some peer reviewed, where instructors or developers
      can submit materials for widespread use. First pilot project with the aim to
      introduce tele-education in biomedical curricula in Bosnia and Herzegovina was
      initiated by Department for Medical Informatics at Medical Faculty in Sarajevo in
      2002 and has been developing since. Faculty member's skills in creating tele
      education differ from those needed for traditional teaching and faculty rewards
      must recognize this difference and reward the effort. Tele-education and use of
      computers will have an impact of future medical practice in a life long learning.
      Bologna process, which started last years in European countries, provide us to
      promote and introduce modern educational methods of education at biomedical
      faculties in Bosnia and Herzegovina. Cathedra of Medical informatics and Cathedra
      of Family medicine at Medical Faculty of University of Sarajevo started to use
      Web based education as common way of teaching of medical students. Satisfaction
      with this method of education within the students is good, but not yet suitable
      for most of medical disciplines at biomedical faculties in Bosnia and
      Herzegovina.

PMID- 24109155
TI  - The advantages and limitations of international classification of diseases,
      injuries and causes of death from aspect of existing health care system of bosnia
      and herzegovina.
AB  - CONFLICT OF INTEREST: NONE DECLARED. INTRODUCTION: The International
      classification of diseases (ICD) is the most important classification in
      medicine. It is used by all medical professionals. CONCEPT: The basic concept of
      ICD is founded on the standardization of the nomenclature for the names of
      diseases and their basic systematization in the hierarchically structured
      category. ADVANTAGES AND DISADVANTAGES: The health care provider institutions
      such as hospitals are subjects that should facilitate implementation of medical
      applications that follows the patient medical condition and facts connected with
      him. The definitive diagnosis that can be coded using ICD can be achieved after
      several visits of patient and rarely during the first visit. CONCLUSION: The ICD
      classification is one of the oldest and most important classifications in
      medicine. In the scope of ICD are all fields of medicine. It is used in
      statistical purpose and as a coding system in medical databases.

PMID- 24109156
TI  - Evidence based medicine - new approaches and challenges.
AB  - CONFLICT OF INTEREST: NONE DECLARED Evidence based medicine (EBM) is the
      conscientious, explicit, judicious and reasonable use of modern, best evidence in
      making decisions about the care of individual patients. EBM integrates clinical
      experience and patient values with the best available research information. It is
      a movement which aims to increase the use of high quality clinical research in
      clinical decision making. EBM requires new skills of the clinician, including
      efficient literature-searching, and the application of formal rules of evidence
      in evaluating the clinical literature. The practice of evidence-based medicine is
      a process of lifelong, self-directed, problem-based learning in which caring for
      one's own patients creates the need for clinically important information about
      diagnosis, prognosis, therapy and other clinical and health care issues. It is
      not "cookbook" with recipes, but its good application brings cost-effective and
      better health care. The key difference between evidence-based medicine and
      traditional medicine is not that EBM considers the evidence while the latter does
      not. Both take evidence into account; however, EBM demands better evidence than
      has traditionally been used. One of the greatest achievements of evidence-based
      medicine has been the development of systematic reviews and meta-analyses,
      methods by which researchers identify multiple studies on a topic, separate the
      best ones and then critically analyze them to come up with a summary of the best
      available evidence. The EBM-oriented clinicians of tomorrow have three tasks: a)
      to use evidence summaries in clinical practice; b) to help develop and update
      selected systematic reviews or evidence-based guidelines in their area of
      expertise; and c) to enrol patients in studies of treatment, diagnosis and
      prognosis on which medical practice is based.

PMID- 24109157
TI  - Development and evaluation of a computer-based program for assessing quality of
      family medicine teams based on accreditation standards.
AB  - CONFLICT OF INTEREST: NONE DECLARED. INTRODUCTION: Agency for healthcare quality
      and accreditation in Federation of Bosnia and Herzegovina (AKAZ) is authorized
      body in the field of healthcare quality and safety improvement and accreditation
      of healthcare institutions. Beside accreditation standards for hospitals and
      primary health care centers, AKAZ has also developed accreditation standards for
      family medicine teams. METHODS: Software development was primarily based on
      Accreditation Standards for Family Medicine Teams. Seven chapters / topics: (1.
      Physical factors; 2. Equipment; 3. Organization and Management; 4. Health
      promotion and illness prevention; 5. Clinical services; 6. Patient survey; and 7.
      Patient's rights and obligations) contain 35 standards describing expected level
      of family medicine team's quality. Based on accreditation standards structure and
      needs of different potential users, it was concluded that software backbone
      should be a database containing all accreditation standards, self assessment and
      external assessment details. In this article we will present the development of
      standardized software for self and external evaluation of quality of service in
      family medicine, as well as plans for the future development of this software
      package. CONCLUSION: Electronic data gathering and storing enhances the
      management, access and overall use of information. During this project we came to
      conclusion that software for self assessment and external assessment is ideal for
      accreditation standards distribution, their overview by the family medicine team
      members, their self assessment and external assessment.

PMID- 24109158
TI  - Register of oncological diseases in canton sarajevo.
AB  - CONFLICT OF INTEREST: NONE DECLARED. SUMMARY: The register of oncological
      diseases in Canton Sarajevo is important as it can be used to track and improve
      healthcare, especially in older age groups. The oncological registers are a way
      of recording data, suitable as a source of indicators. In the analyzed register,
      1124 new cases of malignancy were recorded. There are slightly more malignant
      diseases in male (53%). The incidence of cancer varies depending of the age of
      patients. This analysis gives us important estimation in the relation of cancer
      morbidity, cancer types, age distribution, demographic factors, cancer stages and
      important cancer risks. The register and the analysis give us a chance for
      correlating and comparing the state of oncological diseases with other countries.

PMID- 24109159
TI  - Medical informatics in a United and healthy europe.

PMID- 24109160
TI  - E-health in bosnia - starting from the ground-up.
AB  - CONFLICT OF INTEREST: NONE DECLARED. SUMMARY: The development of the digital
      Information Communication Technology (ICT) has definitely changed healthcare
      system in all its areas. The development of standardized electronic medical
      record (EMR) make possible other forms of E-Health like transmural care,
      telemedicine etc. In this paper was described Health Information System (HIS) of
      Tuzla Canton and Brcko DC (whose citizens gravitate toward Tuzla Clinical
      Center). Tuzla Clinical Center is the only Clinic for tertiary healthcare in this
      region. To estimate level and types of the HIS, telecommunications and
      information management we have designed questionnaire. Based on this research we
      have presented current state of E-Health in Canton and the most important
      problems in this area. Also, based on this research and our experiences, we have
      identified the main directions of the HIS development, its standardization and
      integration as the base for E-Heath in Bosnia.

PMID- 24109161
TI  - Task force of the European Federation of medical informatics journals:
      background, rationale and purpose.
AB  - CONFLICT OF INTEREST: NONE DECLARED The paper presents an analysis of how EFMI
      disseminates new knowledge and of the active medical informatics journals in EFMI
      member countries, which was carried out as an outcome of the EFMI Council
      meetings in London in 2008, Sarajevo in 2009 and Antalya in 2009 . The analysis
      identifies eight active major informatics journals and several other
      publications. Most are subscription-based and published at least quarterly. There
      is a possibility for the editors to meet regularly and form a community of
      practice with the aim of further improving their effectiveness in disseminating
      new knowledge and best practice in medical informatics. It is feasible to share
      expertise and it may be possible to harmonise several aspects of preparation and
      submission of manuscripts so that some of the identified barriers in publishing
      are reduced.

PMID- 24109162
TI  - Electronic chronic disease registers based on accreditation standards for family
      medicine teams.
AB  - CONFLICT OF INTEREST: NONE DECLARED. SUMMARY: Agency for Quality and
      Accreditation of Federation of Bosnia and Herzegovina (AKAZ) has developed
      computer based chronic disease register based on the accreditation standards in
      order to facilitate maintenance of chronic disease registers in the absence of
      electronic health records, and to speed up and simplify calculation for over 70
      clinical indicators from accreditation standards for family medicine teams. This
      article presents development of the software and its practical use.

PMID- 24109163
TI  - The role of inflammatory mediators in immune-to-brain communication during health
      and disease.

PMID- 24109164
TI  - Consistency in color parameters of a commonly used shade guide.
AB  - OBJECTIVE: The use of shade guides to assess the color of natural teeth
      subjectively remains one of the most common means for dental shade assessment.
      Any variation in the color parameters of the different shade guides may lead to
      significant clinical implications. Particularly, since the communication between
      the clinic and the dental laboratory is based on using the shade guide
      designation. The purpose of this study was to investigate the consistency of the
      L*a*b* color parameters of a sample of a commonly used shade guide. MATERIALS AND
      METHODS: The color parameters of a total of 100 VITAPAN Classical Vacuum shade
      guide (VITA Zahnfabrik, Bad Sackingen, Germany(were measured using a X-Rite
      ColorEye 7000A Spectrophotometer (Grand Rapids, Michigan, USA). Each shade guide
      consists of 16 tabs with different designations. Each shade tab was measured five
      times and the average values were calculated. RESULTS: The DeltaE between the
      average L*a*b* value for each shade tab and the average of the 100 shade tabs of
      the same designation was calculated. Using the Student t-test analysis, no
      significant differences were found among the measured sample. CONCLUSION: There
      is a high consistency level in terms of color parameters of the measured VITAPAN
      Classical Vacuum shade guide sample tested.

PMID- 24109165
TI  - The effect of root canal sealers and timing of cementation on the microlekage of
      the parapost luted with resin cement.
AB  - OBJECTIVES: The objectives of the study were to study the effect of root canal
      sealers either eugenol or non-eugenol and timing of cementation on microleakage
      of the parapost luted with resin cement. MATERIALS AND METHODS: Seventy extracted
      human, single-rooted teeth were instrumented using a crown-down technique. All
      teeth were instrumented up to a size 50 .04 taper ProFile followed by the use of
      Gates Glidden drills from size 2 up to 5. Following instrumentation, the teeth
      were randomly divided into four experimental groups of fifteen teeth each, based
      on type of root canal sealer (eugenol or non-eugenol sealer) and timing of post
      cementation (immediate or delayed). The remaining ten teeth were divided into two
      control groups with five teeth per group. All teeth were tested for microleakage
      using a fluid filtration method. RESULTS: The microleakage of the paraposts luted
      with resin cement increased over time, irrespective of sealer type or timing of
      post cementation. Immediate post cementation following obturation with AH26 (non
      eugenol sealer) produced the least microleakage at all three time periods at 24
      h, 2 months and 3 months. CONCLUSIONS: The microleakage paraposts luted with
      resin cement was not influenced by either sealer type or timing of post
      placement. All experimental groups demonstrated a significant increase in
      microleakage over time as well as the presence of voids at the resin-dentin
      interface.

PMID- 24109166
TI  - The effect of commonly used types of coffee on surface microhardness and color
      stability of resin-based composite restorations.
AB  - OBJECTIVE: This study assessed the influence of commonly used types of coffee, in
      Saudi Arabia, on surface microhardness and color stability of microhybrid resin
      based composite (Filtek Z250), nanofilled resin-based composite (Filtek Supreme)
      and organic modified ceramic composite (Ormocer). MATERIALS AND METHODS: A total
      of 75 disk-shaped specimens were fabricated (25 discs from each type of
      material). After initial color and microhardness recording, samples were randomly
      divided into five groups (n = 5). Four groups of specimens from each material
      were immersed in 1 of 4 types of coffee (American, Arabic, Turkish and Espresso
      coffee) and the fifth group was stored in saline to serve as control. The
      specimens were immersed in the different types of coffee for 3 weeks. At the end
      of the test period, surface microhardness and color were measured again. RESULTS:
      It was observed that there is no significant difference in microhardness of the
      three tested materials after immersion in the different types of coffee. However,
      all resin-based materials showed significant color change when compared to
      control (saline). Filtek Z250 showed the least color change among the three
      materials followed by Ormocer. On the other hand, Filtek Supreme was the most
      common material prone to discoloration. Espresso coffee caused the most change in
      color followed by Turkish then American coffee. Nevertheless, Arabic coffee
      caused the least color change of the three materials. CONCLUSIONS: Color
      stability of resin-based materials is affected by their different material
      composition.

PMID- 24109167
TI  - Different techniques of transconjunctival cannulated vitrectomy versus
      conventional non-cannulated vitrectomy in various vitreoretinal disorders.
AB  - PURPOSE: To evaluate the safety and efficacy of different methods of
      transconjunctival cannulated vitrectomy versus conventional non-cannulated
      vitrectomy in various vitreoretinal disorders. METHODS: A prospective randomized
      study was done from August 2009 to February 2011. The study included 129 eyes of
      122 patients, randomly divided into four groups. Group 1 comprised 34 eyes
      operated on using transconjunctival 20-gauge cannula Claes system. Group 2
      comprised 32 eyes operated on using transconjunctival cannulated 23 gauge system.
      Group 3 comprised 27 eyes operated on using combined 20-gauge non-cannulated and
      23-gauge transconjunctival cannulated system. Group 4 comprised 36 eyes operated
      on using conventional non-cannulated 20-gauge system. RESULTS: The four groups
      were demographically similar. Anatomical outcome was achieved in all cases.
      Vision was improved in 29 eyes (85.3%) in group 1, 23 eyes (71.9%) in group 2, 19
      eyes (70.4%) in group 3, and 26 eyes (72.2%) in group 4. There was no statistical
      difference between the four groups 1-day postoperative (P=0.405) and 1-week
      postoperative intraocular pressure (P=0.254). The number of sutureless
      sclerotomies was 68 (66.6%) in group 1, 78 (81.3%) in group 2, 50 (61.8%) in
      group 3, and 0 in group 4. Hypotony occurred in one eye (2.9%) in group 1, three
      eyes (9.4%) in group 2, two eyes (7.4%) in group 3, and no eyes in group 4.
      Operative endophthalmitis did not occur in any one of the four groups.
      CONCLUSION: Final anatomical and functional outcomes were not related to the type
      of sclerotomy used (cannulated or non-cannulated), the gauge used (20 or 23), the
      route (transconjunctival or transscleral), or type of suture used. The advantages
      of small-gauge transconjunctival vitrectomy were patient comfort, early
      ambulation, and preservation of the conjunctiva. This should be weighed against
      the cost of this cannula system.

PMID- 24109168
TI  - Peripheral laser iridoplasty opens angle in plateau iris by thinning the cross
      sectional tissues.
AB  - Plateau iris syndrome has been described as persistent angle narrowing or
      occlusion with intraocular pressure elevation after peripheral iridotomy due to
      the abnormal plateau iris configuration. Argon laser peripheral iridoplasty
      (ALPI) is an effective adjunct procedure to treat plateau iris syndrome. Classic
      theory suggests that the laser causes the contraction of the far peripheral iris
      stroma, "pulls" the iris away from the angle, and relieves the iris-angle
      apposition. We report a case of plateau iris syndrome that was successfully
      treated with ALPI. Spectral domain optical coherence tomography confirmed the
      angle was open at areas with laser treatment but remained appositionally closed
      at untreated areas. Further analysis suggested significant cross-sectional
      thinning of the iris at laser-treated areas in comparison with untreated areas.
      The findings indicate that APLI opens the angle, not only by contracting the iris
      stroma, but also by thinning the iris tissue at the crowded angle. This is
      consistent with the ALPI technique to aim at the iris as far peripheral as
      possible. This case also suggests that spectral domain optical coherence
      tomography is a useful adjunct imaging tool to gonioscopy in assessing the angle
      condition. 

PMID- 24109169
TI  - Safety and effectiveness of a glistening-free single-piece hydrophobic acrylic
      intraocular lens (enVista).
AB  - PURPOSE: To evaluate the safety and effectiveness of a single-piece hydrophobic
      acrylic intraocular lens (IOL; enVista model MX60; Bausch & Lomb, Rochester, NY,
      USA) when used to correct aphakia following cataract extraction in adults.
      METHODS: This was a prospective case series (NCT01230060) conducted in private
      practices in the US. Eligible subjects were adult patients with age-related
      cataract amenable to treatment with standard phacoemulsification/extracapsular
      cataract extraction. With follow-up of 6 months, primary safety and effectiveness
      end points included the rates of US Food and Drug Administration (FDA)-defined
      cumulative and persistent adverse events and the percentage of subjects who
      achieved best-corrected visual acuity (BCVA) of 20/40 or better at final visit.
      To evaluate rotational stability, subjects were randomized (1:1:1:1) to have the
      lens implanted in one of four axis positions in 45 degrees  increments. RESULTS:
      A total of 122 subjects were enrolled. The rate of cumulative and persistent
      adverse events did not significantly exceed historical controls, as per FDA draft
      guidance. At the final postoperative visit, all subjects (100%) achieved a BCVA
      of 20/40 compared with the FDA historical control of 96.7%. Rotation of the IOL
      between the two final follow-up visits was <=5 degrees  for 100% of eyes, and
      refractive stability was demonstrated. A low evaluation of posterior capsule
      opacification score was demonstrated, and no glistenings of any grade were
      reported for any subject at any visit. CONCLUSION: This study demonstrated the
      safety and effectiveness of the MX60 IOL. Favorable clinical outcomes included
      preserved BCVA, excellent rotational and refractive stability, no glistenings,
      and a low evaluation of posterior capsule opacification score.

PMID- 24109170
TI  - The role of topical vitamin A in promoting healing in surface refractive
      procedures: a prospective randomized controlled study.
AB  - AIM: To evaluate the effect of topical vitamin A supplementation on corneal re
      epithelialization time, postoperative pain, visual acuity, and haze following
      photorefractive keratectomy (PRK). PATIENTS AND METHODS: This prospective study
      included 32 patients. For each patient, one eye was randomized to the vitamin A
      group and the fellow eye to the non-vitamin A group (control group). Eyes in the
      vitamin A group received perioperative topical vitamin A (retinol palmitate, 250
      IU/g VitAPOS eye ointment [AFT Pharmaceuticals Pty, Ltd, Sydney, NSW, Australia])
      in addition to the classic treatment for PRK. Clinical outcomes were evaluated up
      to 3 months after PRK. RESULTS: There was no difference in the mean time to
      complete healing between the vitamin A group and the control group (3.36 +/- 0.6
      days in the control group; 3.42 +/- 0.7 days in the vitamin A group; P = 0.854).
      Mean postoperative pain at the 48-hour visit was 4.35 +/- 1.42 over 10 in the
      control group, and 4.42 +/- 1.37 over 10 in the vitamin A group, with no
      difference between the two groups (P = 0.589). Subepithelial haze evaluated at 3
      months postoperatively did not differ between the two groups (P = 0.960). Also,
      visual and refractive outcomes were not different between the two groups 3 months
      postoperatively. CONCLUSION: Topical vitamin A supplementation did not affect re
      epithelialization time, postoperative pain, corneal haze formation, or visual
      outcomes after PRK.

PMID- 24109171
TI  - Changes in retinal nerve fiber layer thickness following mechanical microkeratome
      assisted versus femtosecond laser-assisted LASIK.
AB  - PURPOSE: To study the influence of the transient elevation of intraocular
      pressure during suction in laser-assisted in situ keratomileusis (LASIK) on the
      retinal nerve fiber layer (RNFL) thickness both in microkeratome assisted and
      femotsecond (FS) LASIK. PATIENTS AND METHODS: An interventional case series that
      included 40 eyes suffering from myopia who were candidates for LASIK. All
      underwent Wave Front Guided LASIK by the same surgeon using the VisX CustomVue
      platform. A corneal flap was created in 20 eyes using a mechanical microkeratome
      Moria M2 (MMK), while the IFS IntraLaseTM was used in the remaining 20 eyes. Mean
      suction time was recorded from "Suction ON" to "Suction OFF" time. Optic cube and
      RNFL thickness analysis using Spectral Domain Optical Coherence Tomography (SD
      OCT) Cirrus-HD was completed before, and 1 month after LASIK. RESULTS: The study
      included 40 eyes of 20 patients. All were females with mean age 33.5 +/- 6.4
      years. Mean preoperative spherical equivalent was -3.62 +/- 2.31D. Average
      preoperative RNFL thickness was 94.6 +/- 12.1MUm in MMK group while the
      postoperative average thickness was 95.1 +/- 11.9 um with no statistically
      significant difference (P-value: 0.37). Average preoperative RNFL thickness was
      108.28 +/- 8.4 MUm in FS group compared to 108.38 +/- 11.2 MUm in the
      postoperative average with no statistically significant difference (P-value:
      0.94). Mean "Suction ON" to "Suction OFF" time was 22 seconds in the MMK group
      compared to 41 seconds in the FS group. CONCLUSION: The rise of intraocular
      pressure during application of suction ring in LASIK surgery does not affect the
      RNFL thickness as measured by SD-OCT, whether the flap is created by MMK or FS.

PMID- 24109172
TI  - Photorefractive keratectomy in patients with mild to moderate stable keratoconus:
      a five-year prospective follow-up study.
AB  - BACKGROUND: The purpose of this study was to evaluate the visual outcome of
      photorefractive keratectomy (PRK) in patients with mild to moderate stable
      keratoconus and to assess the risk of progression of the disease after the
      excimer laser procedure. METHODS: In this prospective study, carried out at the
      Clemenceau Medical Center, an affiliate of Johns Hopkins International, in
      Beirut, Lebanon, 119 eyes from 72 patients with grade 1-2 keratoconus (Amsler
      Krumeich classification) underwent PRK. Forty-seven patients had both eyes
      treated and 25 patients had one eye treated. The procedure was done using the
      Wavelight Eye Q Excimer laser. Uncorrected and best-corrected visual acuity,
      corneal topography, and pachymetry were assessed before the procedure and 3, 6,
      12, 36, and 60 months after the procedure. RESULTS: Mean uncorrected visual
      acuity showed a statistically significant improvement (P < 0.05) at one, 3, and 5
      years follow-up. One hundred and seventeen eyes (98.3%) showed no progression
      while two eyes (1.7%) showed progression of the disease at 5 years follow-up, as
      documented by corneal topography and pachymetry. These two eyes were treated with
      corneal collagen crosslinking. CONCLUSION: PRK in mild to moderate keratoconus is
      a safe and effective procedure for improving uncorrected vision in patients with
      mild refractive errors. However, close follow-up of patients is needed to detect
      any progression of the disease. Longer follow-up is needed to assess the overall
      effect of this procedure on progression of the disease.

PMID- 24109173
TI  - Effects of topical bevacizumab application on early bleb failure after
      trabeculectomy: observational case series.
AB  - BACKGROUND: The aim of this study was to evaluate the influence of topical
      bevacizumab on the formation and function of filtering blebs in eyes with early
      bleb failure after antiglaucoma surgery. METHODS: Of all patients who underwent
      mitomycin-augmented trabeculectomy for glaucoma in the Department of
      Ophthalmology at the Medical University in Lublin, Poland, between March 2009 and
      March 2010, a total of 21 eyes from 20 patients with injected filtration bleb 9.8
      +/- 4.7 days after surgery were included in this observational case series. All
      patients were treated with standard steroid therapy and topical bevacizumab 5
      mg/mL five times a day for 20.9 +/- 9.8 days. Patients were followed up every
      other day, and a full eye examination was performed 14, 30, 60, and 180 days
      after initiation of treatment. Blebs were evaluated for vascularity by slit-lamp
      examination with concomitant photographic documentation and intraocular pressure
      measurement. RESULTS: Elevated functional bleb with significantly reduced
      vascularity was present in 16 eyes, and was flat and nonfunctional in five eyes.
      Intraocular pressure in all eyes decreased from a mean of 26.6 +/- 9.6 mmHg
      before surgery to 14.6 +/- 7.7 mmHg and 15.8 +/- 8.3 mmHg at 2 and 6 months after
      surgery, respectively. Filtration bleb leak was noted in three eyes while on
      treatment with bevacizumab. CONCLUSION: Topical application of bevacizumab might
      favor functional bleb formation after trabeculectomy in eyes with a high risk of
      failure.

PMID- 24109174
TI  - Small-aperture corneal inlay in patients with prior radial keratotomy surgeries.
AB  - This paper describes the 3-month results of two patients who underwent KAMRATM
      (AcuFocus, Inc, Irvine, CA, USA) inlay implantation surgery with a history of
      prior radial keratotomy. The refractive error just before KAMRA inlay
      implantation was corrected in one patient with a laser-assisted in situ
      keratomileusis (LASIK) procedure. The post-inlay implantation surgery results
      showed effective uncorrected near visual acuity outcomes with no impact on
      uncorrected distance visual acuity in both patients. 

PMID- 24109175
TI  - Changes in retinal nerve fiber layer and optic disc algorithms by optical
      coherence tomography in glaucomatous Arab subjects.
AB  - PURPOSE: To assess the difference in retinal nerve fiber layer (RNFL) and optic
      disc algorithms between glaucomatous and normal Arab subjects using optical
      coherence tomography (OCT). METHODS: RNFL thickness and optic disc parameters
      were obtained in 65 patients aged 50.1 +/- 7.7 years. Percentage differences in
      all parameters were calculated and analyzed between groups. RESULTS: The mean
      RNFL thickness around the disc and at all quadrants was significantly thinner in
      glaucomatous eyes than in normal eyes (P < 0.01). The greatest decrease in RNFL
      thickness was observed at the inferior (39.5%) and superior (39.3%) quadrants and
      at 1 o'clock (43%) and 5 o'clock (40%) hour sectors. Significant differences were
      observed between glaucomatous and control eyes in all disc parameters (P < 0.005)
      assessed. The disc area, cup area, mean cup/disc ratio, and vertical and
      horizontal cup/disc ratios were significantly larger (P < 0.01), whereas the
      vertical integrated rim area, horizontal integrated rim width, and rim area were
      significantly smaller (P < 0.001) in glaucomatous eyes than in normal eyes.
      CONCLUSION: Stratus OCT is still a valuable tool in the diagnosis of early
      glaucoma changes and, as such, its use should be encouraged in glaucoma clinics
      in Saudi Arabia. The best OCT parameters for detecting early glaucoma change were
      RNFL thickness in the inferior, superior, and 1 o'clock hour sector; the cup
      area; and the vertical integrated rim area of the optic disc.

PMID- 24109176
TI  - Descemet's stripping and non-Descemet's stripping automated endothelial
      keratoplasty for microcornea using 6.0 mm donor grafts.
AB  - BACKGROUND: The purpose of this paper is to report our experience of Descemet's
      stripping and non-Descemet's stripping automated endothelial keratoplasty
      (DSAEK/nDSAEK) for microcorneas using 6.0 mm donor grafts. METHODS: Three eyes of
      two patients (a 56-year-old woman and a 59-year-old woman) with microcornea and
      suffering from bullous keratopathy were treated with either DSAEK or nDSAEK. A
      small donor graft (6.0 mm) was inserted into the anterior chamber using a double
      glide (Busin glide and intraocular lens sheet glide) donor insertion technique.
      Both patients were followed for at least 12 months. Clinical outcomes, including
      intraoperative and postoperative complications, visual acuity, and endothelial
      cell density were evaluated. RESULTS: In all three cases (100%), no
      intraoperative complications were noted. In one case with a flat keratometry
      value (32.13 D), a partial donor detachment was noted one day postoperatively,
      but it was reattached by rebubbling. In another case, rejection was noted 8
      months postoperatively, but treatment with systemic corticosteroids was
      successful. A clear cornea remained in all three cases (100%), with best
      corrected visual acuity greater than 20/100 (mean 20/50) at 12 months. Mean
      postoperative endothelial cell counts were 2,603 +/- 18 cells/mm(2) at 6 months
      (7.4% decrease from preoperative donor cell counts) and 1,799 +/- 556 cells/mm(2)
      at 12 months (36.5% decrease). CONCLUSION: We report for the first time the
      successful use of a small donor graft (6.0 mm) for DSAEK/nDSAEK in cases of
      microcornea. Additional stud ies using a large number of patients are required to
      evaluate fully the potential advantages and drawbacks of small diameter donor
      grafts for microcornea.

PMID- 24109177
TI  - New structure-activity relationships of chalcone inhibitors of breast cancer
      resistance protein: polyspecificity toward inhibition and critical substitutions
      against cytotoxicity.
AB  - Adenosine triphosphate-binding cassette subfamily G member 2 (ABCG2) plays a
      major role in cancer cell multidrug resistance, which contributes to low efficacy
      of chemotherapy. Chalcones were recently found to be potent and specific
      inhibitors, but unfortunately display a significant cytotoxicity. A cellular
      screening against ABCG2-mediated mitoxantrone efflux was performed here by flow
      cytometry on 54 chalcone derivatives from three different series with a wide
      panel of substituents. The identified leads, with submicromolar IC50 (half
      maximal inhibitory concentration) values, showed that the previously identified
      2'-OH-4',6'-dimethoxyphenyl, as A-ring, could be efficiently replaced by a 2'
      naphthyl group, or a 3',4'-methylenedioxyphenyl with lower affinity. Such a
      structural variability indicates 3polyspecificity of the multidrug transporter
      for inhibitors. At least two methoxyl groups were necessary on B-ring for optimal
      inhibition, but substitution at positions 3, 4, and 5 induced cytotoxicity. The
      presence of a large O-benzyl substituent at position 4 and a 2'-naphthyl as A
      ring markedly decreased the cytotoxicity, giving a high therapeutic ratio, which
      constitutes a critical requirement for future in-vivo assays in animal models.

PMID- 24109178
TI  - A novel dimeric thymosin beta 4 with enhanced activities accelerates the rate of
      wound healing.
AB  - OBJECTIVE: Thymosin beta 4 (Tbeta4) is a peptide with 43 amino acids that is
      critical for repair and remodeling tissues on the skin, eye, heart, and neural
      system following injury. To fully realize its utility as a treatment for disease
      caused by injury, the authors constructed a cost-effective novel Tbeta4 dimer and
      demonstrated that it was better able to accelerate tissue repair than native
      Tbeta4. METHODS: A prokaryotic vector harboring two complete Tbeta4 genes with a
      short linker was constructed and expressed in Escherichia coli. A pilot-scale
      fermentation (10 L) was performed to produce engineered bacteria and the Tbeta4
      dimer was purified by one-step hydrophobic interaction chromatography. The
      activities of the Tbeta4 dimer to promote endothelial cell proliferation,
      migration, and sprouting were assessed by tetramethylbenzidine (methylthiazol
      tetrazolium), trans-well, scratch, and tube formation assays. The ability to
      accelerate dermal healing was assessed on rats. RESULTS: After fermentation, the
      Tbeta4 dimer accounted for about 30% of all the bacteria proteins. The purity of
      the Tbeta4 dimer reached 98% after hydrophobic interaction chromatography
      purification. An average of 562.4 mg/L Tbeta4 dimer was acquired using a 10 L
      fermenter. In each assay, the dimeric Tbeta4 exhibited enhanced activities
      compared with native Tbeta4. Notably, the ability of the dimeric Tbeta4 to
      promote cell migration was almost two times higher than that of Tbeta4. The rate
      of dermal healing in the dimeric Tbeta4-treated rats was approximately 1 day
      faster than with native Tbeta4-treated rats. CONCLUSION: The dimeric Tbeta4
      exhibited enhanced activity on wound healing than native Tbeta4, and the
      purification process was simple and cost-effective. This data could be of
      significant benefit for the high pain and morbidity associated with chronic
      wounds disease. A better strategy to develop Tbeta4 as a treatment for other
      diseases caused by injuries such as heart attack, neurotrophic keratitis, and
      multiple sclerosis was also described.

PMID- 24109180
TI  - The influence of severe hypoalbuminemia on the half-life of vancomycin in elderly
      patients with methicillin-resistant Staphylococcus aureus hospital-acquired
      pneumonia.
AB  - BACKGROUND: Vancomycin (VCM) treatment outcomes depend on the characteristics of
      the patient, and it is well known that hypoalbuminemia is a risk factor for poor
      treatment outcomes, as reported in a previous study. However, the reason that
      severe hypoalbuminemia has an influence on the treatment outcome of VCM remains
      unknown. OBJECTIVE: To elucidate the association between severe hypoalbuminemia
      and VCM treatment outcomes, we examined pharmacokinetic/pharmacodynamic (PK/PD)
      parameters in elderly patients with severe hypoalbuminemia. METHODS: We conducted
      a retrospective observational study of 94 patients with methicillin-resistant
      Staphylococcus aureus (MRSA) hospital-acquired pneumonia who had been treated
      with VCM between January 2006 and December 2012. The 94 patients were divided
      into severe hypoalbuminemia and non-severe hypoalbuminemia groups. The PK/PD
      parameters and treatment outcomes of VCM were compared between the two groups.
      RESULTS: The half-life of VCM in the severe hypoalbuminemia group was
      significantly longer than in the non-severe hypoalbuminemia group (33.2 + 5.4 vs
      24.9 + 1.6; P = 0.049). Area under the concentration curve (AUC)/minimum
      inhibitory concentration (MIC) values of 250-450 and >450 MUg * h/mL were
      significantly associated with 28-day mortality in the severe hypoalbuminemia
      group (P < 0.001), whereas AUC/MIC values of <250 MUg * h/mL were not associated.
      We also detected a significant difference in the increased percentage of
      nephrotoxicity in the severe hypoalbuminemia group (6 of 23 patients [26%])
      compared with the non-severe hypoalbuminemia group (6 of 71 patients [8%]; P <
      0.001). CONCLUSION: These findings indicate that severe hypoalbuminemia
      influences the half-life of VCM and treatment outcomes in elderly patients (>=75
      years of age). To establish a more effective and safer treatment protocol, the
      issue of malnutrition in elderly patients needs to be addressed and improved.

PMID- 24109179
TI  - Advances with microRNAs in Parkinson's disease research.
AB  - Parkinson's disease (PD) is the second-most common age-dependent
      neurodegenerative disorder and is caused by severe degeneration of dopaminergic
      neurons in the substantia nigra pars compacta. Unfortunately, current treatment
      only targets symptoms and involves dopamine replacement therapy, which does not
      counteract progressive degeneration. MicroRNAs (miRNAs) are a class of small RNA
      molecules implicated in post-transcriptional regulation of gene expression during
      development. Recent studies show that miRNAs are playing an important role in the
      pathophysiology of PD. miRNA-based therapy is a powerful tool with which to study
      gene function, investigate the mechanism of the disease, and validate drug
      targets. In this review, we focus on the recent advances of the use of miRNAs in
      the pathogenesis of PD. 

PMID- 24109181
TI  - Sn doping induced enhancement in the activity of ZnO nanostructures against
      antibiotic resistant S. aureus bacteria.
AB  - Highly ionic metal oxide nanostructures are attractive, not only for their
      physiochemical properties but also for antibacterial activity. Zinc oxide (ZnO)
      nanostructures are known to have inhibitory activity against many pathogens but
      very little is known about doping effects on it. The antibacterial activity of
      undoped ZnO and tin (Sn) doped ZnO nanostructures synthesized by a simple,
      versatile, and wet chemical technique have been investigated against Escherichia
      coli, methicillin-resistant Staphylococcus aureus, and Pseudomonas aeruginosa
      bacterial strains. It has been interestingly observed that Sn doping enhanced the
      inhibitory activity of ZnO against S. aureus more efficiently than the other two
      bacterial strains. From cytotoxicity and reactive oxygen species (ROS) production
      studies it is found that Sn doping concentration in ZnO does not alter the
      cytotoxicity and ROS production very much. It has also been observed that undoped
      and Sn doped ZnO nanostructures are biosafe and biocompatible materials towards
      SH-SY5Y Cells. The observed behavior of ZnO nanostructures with Sn doping is a
      new way to prevent bacterial infections of S. aureus, especially on skin, when
      using these nanostructures in creams or lotions in addition to their sunscreen
      property as an ultraviolet filter. Structural investigations have confirmed the
      formation of a single phase wurtzite structure of ZnO. The morphology of ZnO
      nanostructures is found to vary from spherical to rod shaped as a function of Sn
      doping. The excitation absorption peak of ZnO is observed to have a blue shift,
      with Sn doping leading toward a significant tuning in band gap. 

PMID- 24109182
TI  - Dual-degradable disulfide-containing PEI-Pluronic/DNA polyplexes: transfection
      efficiency and balancing protection and DNA release.
AB  - Polymeric gene-delivery vectors to achieve lack of toxicity and a balance between
      protection and DNA release remains a formidable challenge. Incorporating
      intracellular environment-responsive degradable bonds is an appreciable step
      toward developing safer transfection agents. In this study, novel, dual
      degradable polycation copolymers (Pluronic-diacrylate [PA]-polyethyleneimine
      [PEI]-SS) were synthesized through the addition of low molecular weight (800 Da)
      PEI cross-linked with SS (PEI-SS) to PA. Three PA-PEI-SS copolymers (PA-PEI-SS1,
      2, and 3) with different PEI-SS to Pluronic molar ratios were investigated and
      found to strongly condense plasmid DNA into positively charged nanoparticles with
      an average particle size of approximately 200 nm and to possess higher stability
      against DNase I digestion and sodium heparin. Disulfide and ester bonds of the
      copolymers were susceptible to intracellular redox conditions. In vitro
      experiments demonstrated that the PA-PEI-SS copolymers had significantly lower
      cytotoxicity and higher transfection efficiency in both BGC-823 and 293T cell
      lines than the controls of degradable PEI-SS and nondegradable 25 kDa PEI.
      Transfection activity was influenced by the PEI-SS content in the polymers and PA
      PEI-SS1 showed the highest efficiency of the three copolymers. These studies
      suggest that these dual-degradable copolymers could be used as potential
      biocompatible gene delivery carriers. 

PMID- 24109183
TI  - Synergetic effect of functional cadmium-tellurium quantum dots conjugated with
      gambogic acid for HepG2 cell-labeling and proliferation inhibition.
AB  - We prepared and studied novel fluorescent nanocomposites based on gambogic acid
      (GA) and cadmium-tellurium (CdTe) quantum dots (CdTe QDs) modified with
      cysteamine for purpose of cancer cell labeling and combined treatment. The
      nanocomposites were denoted as GA-CdTe. Characterization results indicated that
      the CdTe QDs can readily bind onto cell plasma membranes and then be internalized
      into cancer cells for real-time labeling and tracing of human liver
      hepatocellular carcinoma cell line (HepG2) cells. GA-CdTe significantly enhanced
      drug accumulation in HepG2 cells and inhibited cancer cell proliferation. GA-CdTe
      nanocomposites also improved the drug action of GA molecules in HepG2 cells and
      induced the G2/M phase arrest of the cancer cell cycle, promoting cell apoptosis.
      Given the sensitive, pH-triggered release of GA-CdTe, the side effects of GA
      anticancer agents on normal cells/tissues in the blood circulation markedly
      decreased. Efficient drug release and accumulation in target tumor cells were
      also facilitated. Thus, the fluorescent GA-CdTe offered a new strategy for
      potential multimode cancer therapy and provided new channels for research into
      naturally-active compounds extracted from traditional Chinese medicinal plants. 

PMID- 24109185
TI  - Younger age, female sex, and high number of awakenings and arousals predict
      fatigue in patients with sleep disorders: a retrospective polysomnographic
      observational study.
AB  - BACKGROUND: The Fatigue Severity Scale (FSS) is widely used to assess fatigue,
      not only in the context of multiple sclerosis-related fatigue, but also in many
      other medical conditions. Some polysomnographic studies have shown high FSS
      values in sleep-disordered patients without multiple sclerosis. The Modified
      Fatigue Impact Scale (MFIS) has increasingly been used in order to assess
      fatigue, but polysomnographic data investigating sleep-disordered patients are
      thus far unavailable. Moreover, the pathophysiological link between sleep
      architecture and fatigue measured with the MFIS and the FSS has not been
      previously investigated. METHODS: This was a retrospective observational study (n
      = 410) with subgroups classified according to sleep diagnosis. The statistical
      analysis included nonparametric correlation between questionnaire results and
      polysomnographic data, age and sex, and univariate and multiple logistic
      regression. RESULTS: The multiple logistic regression showed a significant
      relationship between FSS/MFIS values and younger age and female sex. Moreover,
      there was a significant relationship between FSS values and number of arousals
      and between MFIS values and number of awakenings. CONCLUSION: Younger age, female
      sex, and high number of awakenings and arousals are predictive of fatigue in
      sleep-disordered patients. Further investigations are needed to find the
      pathophysiological explanation for these relationships.

PMID- 24109184
TI  - Current approaches to treatments for schizophrenia spectrum disorders, part II:
      psychosocial interventions and patient-focused perspectives in psychiatric care.
AB  - Schizophrenia is a disabling psychiatric illness associated with disruptions in
      cognition, emotion, and psychosocial and occupational functioning. Increasing
      evidence shows that psychosocial interventions for people with schizophrenia, as
      an adjunct to medications or usual psychiatric care, can reduce psychotic
      symptoms and relapse and improve patients' long-term outcomes such as recovery,
      remission, and illness progression. This critical review of the literature was
      conducted to identify the common approaches to psychosocial interventions for
      people with schizophrenia. Treatment planning and outcomes were also explored and
      discussed to better understand the effects of these interventions in terms of
      person-focused perspectives such as their perceived quality of life and
      satisfaction and their acceptability and adherence to treatments or services
      received. We searched major health care databases such as EMBASE, MEDLINE, and
      PsycLIT and identified relevant literature in English from these databases. Their
      reference lists were screened, and studies were selected if they met the criteria
      of using a randomized controlled trial or systematic review design, giving a
      clear description of the interventions used, and having a study sample of people
      primarily diagnosed with schizophrenia. Five main approaches to psychosocial
      intervention had been used for the treatment of schizophrenia: cognitive therapy
      (cognitive behavioral and cognitive remediation therapy), psychoeducation, family
      intervention, social skills training, and assertive community treatment. Most of
      these five approaches applied to people with schizophrenia have demonstrated
      satisfactory levels of short- to medium-term clinical efficacy in terms of
      symptom control or reduction, level of functioning, and/or relapse rate. However,
      the comparative effects between these five approaches have not been well studied;
      thus, we are not able to clearly understand the superiority of any of these
      interventions. With the exception of patient relapse, the longer-term (eg, >2
      years) effects of these approaches on most psychosocial outcomes are not well
      established among these patients. Despite the fact that patients' perspectives on
      treatment and care have been increasingly concerned, not many studies have
      evaluated the effect of interventions on this perspective, and where they did,
      the findings were inconclusive. To conclude, current approaches to psychosocial
      interventions for schizophrenia have their strengths and weaknesses, particularly
      indicating limited evidence on long-term effects. To improve the longer-term
      outcomes of people with schizophrenia, future treatment strategies should focus
      on risk identification, early intervention, person-focused therapy, partnership
      with family caregivers, and the integration of evidence-based psychosocial
      interventions into existing services. 

PMID- 24109186
TI  - Right putamen hemorrhage manifesting as apraxia of eyelid opening.
AB  - PURPOSE: The purpose of this report is to demonstrate a rare clinical
      manifestation of apraxia eyelid opening related to a basal ganglia lesion. CASE
      REPORT: In this study, we report a 91-year-old woman suffering from difficulty in
      eyelid opening after being treated for myocardial ischemia with dual antiplatelet
      medications. She could open her eyelid with fingers touching her forehead. Brain
      computed tomography revealed a right putamen hemorrhage. Surface electromyography
      revealed persistent frontalis muscle contraction during relaxation of orbicularis
      oculi muscles. Apraxia of eyelid opening was diagnosed. Her eyelid symptom
      resolved 2 months later. CONCLUSION: Apraxia of eyelid opening may be caused by
      subcortical hemorrhage of the basal ganglia. In addition to the primary motor
      cortex and supplemental motor area, the basal ganglia may also play a role in
      eyelid opening.

PMID- 24109188
TI  - Left ventricular dysfunction in normotensive type II diabetic patients in Port
      Harcourt, Nigeria.
AB  - BACKGROUND: Diabetes mellitus (DM) is on the increase globally. Cardiovascular
      complications, such as left ventricular dysfunction is a major cause of death in
      patients with type II DM. Prior to the development of symptomatic heart failure,
      subclinical left ventricular dysfunction (systolic and diastolic) may exist for
      some time. AIM: The aim of the study was to determine the prevalence of left
      ventricular dysfunction in non-hypertensive type II DM patients. METHODS: A cross
      sectional study of left ventricular function in 90 normotensive type II diabetes
      mellitus patients using echocardiography was carried out. Healthy normotensive
      controls matched for age, sex, and body mass index were selected for comparison.
      Patients and controls who had hypertension (blood pressure of >140/90 mmHg),
      history of smoking, significant alcohol history, pregnancy, features of thyroid
      disease, or valvular heart disease were excluded. Left ventricular diastolic and
      systolic functions were assessed. RESULTS: Ninety patients, (39 males and 51
      females) and 90 healthy controls (39 males and 51 females) were enrolled. Mean
      age of patients was 50.76 +/- 9.13 years and 51.33 +/- 7.84 years for controls.
      Mean body mass index was 26.88 +/- 4.73 kg/m2 in patients and 27.09 +/- 4.04
      kg/m2 in controls. Mean ejection fraction was 62.4% +/- 8.47% and 68.52% +/-
      7.94% in patients and controls, respectively (P < 0.001). Fourteen (15.56%)
      patients had ejection fraction less than 55% compared to four (4.44%) in controls
      (P < 0.001; odds ratio = 3.96). Impaired diastolic function was found in 65.6% of
      patients compared to 3.3% of controls (P < 0.001). Left ventricular mass index of
      >99 kg/m2 in females and >115 kg/m2 in males was considered abnormal. The left
      ventricular mass index was also higher in patients than in controls (95.17 +/-
      25.67 g/m2 versus 85.40 +/- 18.0 g/m2; P = 0.004). CONCLUSION: Normotensive
      diabetic patients have a high prevalence of left ventricular dysfunction even in
      the absence of cardiac symptoms.

PMID- 24109187
TI  - Role of nucleus accumbens glutamatergic plasticity in drug addiction.
AB  - Substance dependence is characterized by a group of symptoms, according to the
      Diagnostic and Statistical Manual of Mental Disorders, 4th Edition, Text Revision
      (DSM-IV-TR). These symptoms include tolerance, withdrawal, drug consumption for
      alleviating withdrawal, exaggerated consumption beyond original intention,
      failure to reduce drug consumption, expending a considerable amount of time
      obtaining or recovering from the substance's effects, disregard of basic aspects
      of life (for example, family), and maintenance of drug consumption, despite
      facing adverse consequences. The nucleus accumbens (NAc) is a brain structure
      located in the basal forebrain of vertebrates, and it has been the target of
      addictive drugs. Different neurotransmitter systems at the level of the NAc
      circuitry have been linked to the different problems of drug addiction, like
      compulsive use and relapse. The glutamate system has been linked mainly to
      relapse after drug-seeking extinction. The dopamine system has been linked mainly
      to compulsive drug use. The glutamate homeostasis hypothesis centers around the
      dynamics of synaptic and extrasynaptic levels of glutamate, and their impact on
      circuitry from the prefrontal cortex (PFC) to the NAc. After repetitive drug use,
      deregulation of this homeostasis increases the release of glutamate from the PFC
      to the NAc during drug relapse. Glial cells also play a fundamental role in this
      hypothesis; glial cells shape the interactions between the PFC and the NAc by
      means of altering glutamate levels in synaptic and extrasynaptic spaces. On the
      other hand, cocaine self-administration and withdrawal increases the surface
      expression of subunit glutamate receptor 1 (GluA1) of alpha-amino-3-hydroxy-5
      methyl-4-isoxazolepropionic acid (AMPA) receptors at the level of the NAc. Also,
      cocaine self-administration and withdrawal induce the formation of subunit
      glutamate receptor 2 (GluA2), lacking the Ca(2+)-permeable AMPA receptors (CP
      AMPARs) at the level of the NAc. Antagonism of the CP-AMPARs reduces cravings. It
      is necessary to pursue further exploration of the AMPA receptor subunit
      composition and variations at the level of the NAc for a better understanding of
      glutamatergic plastic changes. It is known that cocaine and morphine are able to
      induce changes in dendritic spine morphology by modifying actin cycling. These
      changes include an initial increase in spine head diameter and increases in AMPA
      receptor expression, followed by a second stage of spine head diameter retraction
      and reduction of the AMPA receptors' expression in spines. Besides glutamate and
      dopamine, other factors, like brain-derived neurotrophic factor (BDNF), can
      influence NAc activity and induce changes in dendritic spine density. BDNF also
      induces drug-related behaviors like self-administration and relapse. Neither
      apoptosis nor neurogenesis plays a relevant role in the neurobiological processes
      subjacent to cocaine addiction in adults (rodent or human). Different therapeutic
      drugs like N-acetylcysteine (NAC), modafinil, acamprosate, and topiramate have
      been tested in preclinical and/or clinical models for alleviating drug relapse.
      Moreover, these therapeutic drugs target the glutamatergic circuitry between the
      PFC and the NAc. NAC and acamprosate have shown inconsistent results in clinical
      trials. Modafinil and topiramate have shown some success, but more clinical
      trials are necessary. Based on the current review findings, it could be
      recommendable to explore therapeutic approaches that include synergism between
      different drugs and neurotransmitter systems. The discrepancy in the results of
      some therapeutic drugs between preclinical versus clinical trials for alleviating
      relapse or drug dependence could be linked to the scarce exploration of
      preclinical models that mimic polydrug abuse patterns, for example, cocaine plus
      alcohol. At the clinical level, the pattern of polydrug consumption is a
      phenomenon of considerable frequency. Finally, as a complement at the end, an
      updated summary is included about the role of glutamate in other neuropsychiatric
      disorders (for example, mood disorders, schizophrenia, and others). 

PMID- 24109189
TI  - Comparative effectiveness of a fixed-dose combination of losartan + HCTZ versus
      bisoprolol + HCTZ in patients with moderate-to-severe hypertension: results of
      the 6-month ELIZA trial.
AB  - BACKGROUND: The aim of this study was to compare the antihypertensive efficacy of
      losartan 100 mg + hydrochlorothiazide (HCTZ) 25 mg versus bisoprolol 10 mg + HCTZ
      25 mg and their influence on arterial stiffness and central blood pressure (BP).
      METHODS: Of 60 patients with a mean BP of 173.3 +/- 1.7/98.4 +/- 1.2 mmHg, 59
      were randomized to losartan + HCTZ (n = 32) or bisoprolol + HCTZ (n = 27).
      Amlodipine was added if target BP was not achieved at 1 month, and doxazosin was
      added if target BP was not achieved after 3 months. Body mass index, office and
      24-hour ambulatory BP, pulse wave velocity (carotid-femoral [PWVE] and radial
      [PWVM]), noninvasive central systolic BP, augmentation index (AIx), laboratory
      investigations, and electrocardiography were done at baseline and after 6 months
      of treatment. RESULTS: Losartan + HCTZ was as effective as bisoprolol + HCTZ,
      with target office BP achieved in 96.9% and 92.6% of patients and target 24-hour
      BP in 75% and 66.7% of patients, respectively, after 6 months. Effective
      treatment of BP led to significant lowering of central systolic BP, but this was
      decreased to a significantly (P < 0.05) greater extent by losartan + HCTZ (-23.0
      +/- 2.3 mmHg) than by bisoprolol + HCTZ (-15.4 +/- 2.9 mmHg) despite equal
      lowering of brachial BP. Factors correlated with central systolic BP and its
      lowering differed between the treatment groups. Losartan + HCTZ did not alter
      arterial stiffness patterns significantly, but bisoprolol + HCTZ significantly
      increased AIx. We noted differences in DeltaPWVE, DeltaPWVM, and DeltaAIx between
      the groups in favor of losartan + HCTZ. Decreased heart rate was associated with
      higher central systolic BP and AIx in the bisoprolol + HCTZ group, but was not
      associated with increased AIx in the losartan + HCTZ group. CONCLUSION: Although
      both treatments decreased both office and 24-hour BP, losartan + HCTZ
      significantly decreased central systolic BP and had a more positive influence on
      pulse wave velocity, with a less negative effect of decreased heart rate on AIx
      and central systolic BP.

PMID- 24109191
TI  - A multicenter evaluation of the efficacy and duration of action of alcaftadine
      0.25% and olopatadine 0.2% in the conjunctival allergen challenge model.
AB  - BACKGROUND: The purpose of this study was to evaluate the efficacy and duration
      of action of once-daily dosing with alcaftadine 0.25% ophthalmic solution and
      olopatadine 0.2% ophthalmic solution as compared with placebo in the prevention
      of ocular itching, and to directly compare the efficacy of alcaftadine 0.25% with
      olopatadine 0.2% in the prevention of ocular itching associated with allergic
      conjunctivitis using the conjunctival allergen challenge model. METHODS: Subjects
      with allergic conjunctivitis (n = 127) were enrolled in a multicenter, double
      masked, randomized, active-controlled and placebo-controlled clinical trial.
      Using the conjunctival allergen challenge model, this study was conducted over
      the course of approximately 5 weeks. Subjects were randomized into one of three
      treatment arms: alcaftadine 0.25% ophthalmic solution, olopatadine 0.2%
      ophthalmic solution, or placebo. Study medications were administered twice over
      the course of the trial. The primary efficacy measure for the study was ocular
      itching evaluated by the subject at 3, 5, and 7 minutes post challenge. Secondary
      endpoints, measured at 7, 15, and 20 minutes post challenge, included
      conjunctival, ciliary, and episcleral redness, lid swelling, chemosis, and
      tearing. Duration of action was measured at 16 and 24 hours post-instillation of
      the study medication at visits 3 and 4, respectively. RESULTS: For the primary
      measure of ocular itching, both actives, alcaftadine 0.25% and olopatadine 0.2%,
      were statistically superior to placebo at all three measured time points for both
      the 16-hour and 24-hour measures (P < 0.0001). Eyes treated with alcaftadine
      0.25% had numerically lower mean ocular itching scores than eyes treated with
      olopatadine 0.2% at every time point, and this difference was statistically
      significant at the 3-minute time point 16 hours post instillation (P = 0.026).
      Eyes treated with alcaftadine 0.25% and with olopatadine 0.2% displayed
      significantly less lid swelling relative to placebo at every time point for the
      16-hour and 24-hour post-instillation visits (P < 0.005). Alcaftadine 0.25% was
      the only active treatment that provided statistically significant relief of
      chemosis at every time point of the 24-hour post-instillation visit. CONCLUSION:
      Both the alcaftadine 0.25% and olopatadine 0.2% ophthalmic solutions provided
      highly effective relief of ocular itching at both 16 and 24 hours post
      instillation. Treatment differences between the actives were most pronounced at
      the earliest time point (3 minutes post-challenge) following conjunctival
      allergen challenge (16 hours), when alcaftadine 0.25% ophthalmic solution was
      statistically superior to olopatadine 0.2% ophthalmic solution. Alcaftadine 0.25%
      was the only treatment to provide significant relief from chemosis at both 16 and
      24 hours post-instillation. Both active treatments and placebo were generally
      safe and well tolerated.

PMID- 24109190
TI  - Personalized treatment strategies in glioblastoma: MGMT promoter methylation
      status.
AB  - The identification of molecular genetic biomarkers considerably increased our
      current understanding of glioma genesis, prognostic evaluation, and treatment
      planning. In glioblastoma, the most malignant intrinsic brain tumor entity in
      adults, the promoter methylation status of the gene encoding for the repair
      enzyme O6-methylguanine-DNA methyltransferase (MGMT) indicates increased efficacy
      of current standard of care, which is concomitant and adjuvant chemoradiotherapy
      with the alkylating agent temozolomide. In the elderly, MGMT promoter methylation
      status has recently been introduced to be a predictive biomarker that can be used
      for stratification of treatment regimes. This review gives a short summery of
      epidemiological, clinical, diagnostic, and treatment aspects of patients who are
      currently diagnosed with glioblastoma. The most important molecular genetic
      markers and epigenetic alterations in glioblastoma are summarized. Special focus
      is given to the physiological function of DNA methylation-in particular, of the
      MGMT gene promoter, its clinical relevance, technical aspects of status
      assessment, its correlation with MGMT mRNA and protein expressions, and its place
      within the management cascade of glioblastoma patients. 

PMID- 24109192
TI  - MicroRNA and nephropathy: emerging concepts.
AB  - Micro ribonucleic acids (miRNAs) are short noncoding RNAs that inhibit gene
      expression through the post-transcriptional repression of their target mRNAs.
      Increasing evidence shows that miRNAs have emerged as key players in diverse
      biologic processes. Aberrant miRNA expression is also closely related to various
      human diseases, including kidney diseases. From clinical and experimental animal
      studies, emerging evidence demonstrates a critical role for miRNAs in renal
      pathophysiology. Renal fibrosis is the hallmark of various chronic kidney
      diseases and transforming growth factor beta (TGF-beta) is recognized as a vital
      mediator of renal fibrosis because it can induce production of extracellular
      matrix proteins resulting in dysfunction of the kidneys. The relationship between
      TGF-beta signaling and miRNAs expression during renal diseases has been recently
      established. TGF-beta positively or negatively regulates expression of several
      miRNAs, such as miR-21, miR-192, miR-200, and miR-29. Both miR-192 and miR-21 are
      positively regulated by TGF-beta1/Smad3 signaling and play a pathological role in
      kidney diseases. Conversely, members of both miR-29 and miR-200 families are
      negatively regulated by TGF-beta/Smad3 and play a protective role in renal
      fibrosis by inhibiting the deposition of extracellular matrix and preventing
      epithelial-to-mesenchymal transition, respectively. Clinically, levels of miRNAs
      in circulation and urine may be potential biomarkers for detecting early stages
      of renal diseases and targeting miRNAs also provides promising therapeutic
      effects in rodent models of chronic kidney disease. However, mechanisms and roles
      of miRNAs under disease conditions remain to be explored. Thus, understanding the
      function of miRNAs in the pathogenesis of kidney diseases may offer an innovative
      approach for both early diagnosis and treatment of renal diseases. 

PMID- 24109193
TI  - Patient selection and targeted treatment in the management of platinum-resistant
      ovarian cancer.
AB  - Ovarian cancer (OC) has the highest mortality rate of any gynecologic cancer, and
      patients generally have a poor prognosis due to high chemotherapy resistance and
      late stage disease diagnosis. Platinum-resistant OC can be treated with cytotoxic
      chemotherapy such as paclitaxel, topotecan, pegylated liposomal doxorubicin, and
      gemcitabine, but many patients eventually relapse upon treatment. Fortunately,
      there are currently a number of targeted therapies in development for these
      patients who have shown promising results in recent clinical trials. These
      treatments often target the vascular endothelial growth factor pathway (eg,
      bevacizumab and aflibercept), DNA repair mechanisms (eg, iniparib and olaparib),
      or they are directed against folate related pathways (eg, pemetrexed,
      farletuzumab, and vintafolide). As many targeted therapies are only effective in
      a subset of patients, there is an increasing need for the identification of
      response predictive biomarkers. Selecting the right patients through biomarker
      screening will help tailor therapy to patients and decrease superfluous treatment
      to those who are biomarker negative; this approach should lead to improved
      clinical results and decreased toxicities. In this review the current targeted
      therapies used for treating platinum-resistant OC are discussed. Furthermore, use
      of prognostic and response predictive biomarkers to define OC patient populations
      that may benefit from specific targeted therapies is also highlighted. 

PMID- 24109194
TI  - Parental risk factors for the development of pediatric acute and chronic
      postsurgical pain: a longitudinal study.
AB  - BACKGROUND: The goal of this longitudinal study was to examine the associations
      among psychological factors and pain reports of children and their parents over
      the 12 month period after pediatric surgery. MATERIALS AND METHODS: Included in
      the study were 83 children aged 8-18 years undergoing major surgery. In each
      case, the child and one of their parents completed measures of pain intensity and
      unpleasantness, psychological function, and functional disability at 48-72 hours,
      2 weeks (child only), 6 months, and 12 months after surgery. RESULTS: The
      strength of the correlation coefficients between the psychological measures of
      the parent and their child increased significantly over time. There was a fair
      level of agreement between parent ratings of child acute and chronic pain (6
      months after surgery) and the child's actual ratings. Parent and child pain
      anxiety scores 48-72 hours after surgery interacted significantly to predict pain
      intensity, pain unpleasantness, and functional disability levels 2 weeks after
      discharge from hospital. Parent pain catastrophizing scores 48-72 hours after
      surgery predicted child pain intensity reports 12 months later. CONCLUSION: These
      results raise the possibility that as time from surgery increases, parents exert
      greater and greater influence over the pain response of their children, so that
      by 12 months postsurgery mark, parent pain catastrophizing (measured in the days
      after surgery) is the main risk factor for the development of postsurgical pain
      chronicity.

PMID- 24109195
TI  - Hyperacute drug-induced hepatitis with intravenous amiodarone: case report and
      review of the literature.
AB  - Amiodarone is a benzofuran class III antiarrhythmic drug used to treat a wide
      spectrum of ventricular tachyarrhythmias. The parenteral formulation is prepared
      in polysorbate 80 diluent. We report an unusual case of acute elevation of
      aminotransaminase concentrations after the initiation of intravenous amiodarone.
      An 88-year-old Caucasian female developed acute hepatitis and renal failure after
      initiating intravenous amiodarone for atrial fibrillation with a rapid
      ventricular response in the setting of acutely decompensated heart failure and
      hepatic congestion. Liver transaminases returned to baseline within 7 days after
      discontinuing the drug. Researchers hypothesized that this type of injury is
      related to liver ischemia with possible superimposed direct drug toxicity. The
      CIOMS/RUCAM scale identifies our patient's acute hepatitis as a highly probable
      adverse drug reaction. Future research is needed to understand the mechanisms by
      which hyperacute drug toxicity occurs in the setting of impaired hepatic
      perfusion and venous congestion. 

PMID- 24109197
TI  - Ospemifene for the treatment of dyspareunia associated with vulvar and vaginal
      atrophy: potential benefits in bone and breast.
AB  - Ospemifene is a selective estrogen receptor modulator (SERM), or estrogen
      receptor agonist/antagonist, that was recently approved by the US Food and Drug
      Administration for the treatment of dyspareunia associated with vulvar and
      vaginal atrophy, a chronic condition that affects up to 60% of postmenopausal
      women. Ospemifene is the first and only nonestrogen compound approved for this
      indication. Compared with other approved SERMs, such as tamoxifen, toremifene,
      bazedoxifene, and raloxifene, the estrogen-like effects of ospemifene in the
      vaginal epithelium are unique. This review first discusses the rationale for
      developing ospemifene, including its mechanism of action, and then focuses on the
      clinical development of ospemifene for the treatment of dyspareunia associated
      with vulvar and vaginal atrophy. Included are discussions of the effects of
      ospemifene on the endometrium, serum lipids, coagulation markers, bone, and
      breast cancer. In conclusion, ospemifene is a SERM with a unique estrogen
      agonist/antagonist tissue profile that was recently approved in the US for the
      treatment of dyspareunia associated with vulvar and vaginal atrophy in
      postmenopausal women. Ospemifene warrants further clinical investigation for the
      treatment and prevention of osteoporosis and breast cancer. 

PMID- 24109196
TI  - Management of urolithiasis in pregnancy.
AB  - Kidney stones are very common and unfortunately do not spare the pregnant
      population. Anatomical and pathophysiological changes occur in the pregnant
      female that alter the risk for development of nephrolithiasis. Acute renal colic
      during pregnancy is associated with significant potential risks to both mother
      and fetus. Diagnosis is often challenging because good imaging options without
      radiation use are limited. Management of diagnosed nephrolithiasis is unique in
      the pregnant population and requires multi-disciplinary care. Herein, we review
      the metabolic alterations during pregnancy that may promote kidney stone
      formation, the complications associated with acute renal colic in the pregnant
      state, and our proposed diagnostic and management algorithms when dealing with
      this clinical scenario. 

PMID- 24109198
TI  - Offering extended use of the combined contraceptive pill: a survey of specialist
      family planning services.
AB  - BACKGROUND: The purpose of this study was to determine attitudes to, and
      provision of, extended regimens for taking the combined oral contraceptive pill
      (COC) by specialist contraception practitioners from three contrasting specialist
      contraception services in London. METHODS: An online cross-sectional survey was
      administered to all doctors and nurses, who counsel, provide, or prescribe the
      oral contraceptive pill at each clinic. RESULTS: A total of 105 clinicians
      received the questionnaire and 67 (64%) responded. Only one of three clinics
      initiated and maintained guidelines for extended COC use. In that service, 60% of
      staff prescribing COC advised more than 50% of patients regarding alternative COC
      regimens. In the other two services, this was discussed with 20% and 6% of
      patients, respectively (P < 0.001). The reasons for prescribing extended use
      included cyclic headaches, menorrhagia, patient request, menstrual-related
      cramps, and endometriosis, and did not differ between the three different
      settings. The most common extended regimens were 63 pills or continuous use until
      bleeding occurs, followed by a hormone-free interval. Concerns highlighted by
      providers and patients were "unhealthy not to have a monthly bleed", "future
      fertility", and "breakthrough bleeding". Such comments highlight the need for
      further information for providers and patients. CONCLUSION: There is growing
      evidence, backed by national guidance, about extended COC use, but routine
      provision of this information is patchy and varies ten-fold, even within
      specialist family planning services. Targeted training, use of service
      guidelines, and implementation research will be needed to extend patient choice
      of different COC regimens and change clinical practice.

PMID- 24109199
TI  - Acoustic radiation force impulse imaging with Virtual TouchTM tissue
      quantification: mean shear wave velocity of malignant and benign breast masses.
AB  - Acoustic radiation force impulse imaging (ARFI) with Virtual TouchTM tissue
      quantification (VTTQ) enables the determination of shear wave velocity (SWV) in
      meters per second (m/s). The aim of our study was to describe the mean SWV in
      normal breast tissue and various breast masses. We performed measurements of SWV
      with ARFI VTTQ in 145 breast masses (57 malignant, 88 benign) and in the adjacent
      breast parenchyma and adipose tissue. The mean SWV as well as the rate of
      successful measurements were analyzed. The difference between adipose tissue and
      parenchyma was statistically significant (3.05 versus 3.65 m/s) (P < 0.001).
      Focusing on breast masses, numerous measurements exceeded the upper limit of
      possible measurement (>=9.10 m/s, indicated as "X.XX m/s"). Nevertheless, the
      difference between the malignant and benign masses was statistically significant
      (8.38 +/- 1.99 m/s versus 5.39 +/- 2.95 m/s) (P < 0.001). The best diagnostic
      accuracy (75.9%) was achieved when the cutoff point for malignancy was set to
      9.10 m/s in ARFI VTTQ. This implies that the SWV was regarded as suspicious when
      the upper limit of possible measurement was exceeded and the machine returned the
      value X.XX m/s. In conclusion, ARFI VTTQ is a feasible method for measurement of
      SWV in a region of interest. Furthermore, we propose the event of a highly
      elevated SWV as a significant criterion for malignancy. However, the method is
      technically not yet fully developed, and the problem of unsuccessful measurements
      must still be solved. 

PMID- 24109200
TI  - Counseling about gestational weight gain and healthy lifestyle during pregnancy:
      Canadian maternity care providers' self-evaluation.
AB  - INTRODUCTION: There is discord between the recall of maternity care providers and
      patients when it comes to discussion of gestational weight gain (GWG) and obesity
      management. Few women report being advised on GWG, physical activity (PA), and
      nutrition, yet the majority of health care providers report discussing these
      topics with patients. We evaluated whether various Canadian maternal health care
      providers can identify appropriate GWG targets for patients with obesity and
      determine if providers report counseling on GWG, physical activity, and
      nutrition. METHODS: A valid and reliable e-survey was created using SurveyMonkey
      software and distributed by the Society of Obstetricians and Gynaecologists of
      Canada listserve. A total of 174 health care providers finished the survey.
      Respondents self-identified as general practitioners, obstetricians, maternal
      fetal medicine specialists, midwives, or registered nurses. RESULTS: GWG
      recommendations between disciplines for all body mass index categories were
      similar and fell within Health Canada/Institute of Medicine (IOM) guidelines. Of
      those who answered this question, 110/160 (68.8%) were able to correctly identify
      the maximum IOM GWG recommended for patients with obesity, yet midwives tended to
      recommend 0.5-1 kg more GWG (P = 0.05). PA counseling during pregnancy differed
      between disciplines (P < 0.01), as did nutrition counseling during pregnancy (P <
      0.05). CONCLUSION: In contrast to patient reports, the majority of health care
      providers document counseling on GWG, PA, and nutrition and appropriately
      identify GWG limits for obese patients. However, the content and quality of the
      discourse between patient and provider warrants further investigation.

PMID- 24109202
TI  - Determination of lamivudine and stavudine in pharmaceutical preparations using
      chemometrics-assisted spectrophotometry.
AB  - A simple chemometrics-assisted spectrophotometric method for the simultaneous
      determination of lamivudine and stavudine in pharmaceutical tablets is described.
      The UV absorption spectra of the studied drugs, in the range of 200-310 nm,
      showed a considerable degree of spectral overlapping ([Di ](0.5) = 94.9%).
      Resolution of the mixture has been accomplished by using classical least-squares
      regression analysis (CLS) and principle components regression analysis methods
      (PCR). Beer's law was obeyed for both drugs in the general concentration ranges
      of 2-12 and 3-15 MUg ml(-1) for lamivudine and stavudine, respectively. The
      proposed methods were successfully applied for the determination of the two drugs
      in laboratory prepared mixtures. The overall recoveries percent were found 98.58
      +/- 1.53-101.30 +/- 1.35 (CLS) and 98.62 +/- 1.65-101.13 +/- 1.04 (PCR) for
      lamivudine and 98.43 +/- 1.62-99.42 +/- 1.55 (CLS) and 98.23 +/- 1.97-101.20 +/-
      1.79 (PCR) for stavudine, respectively. The commercial tablets percentage content
      was found 98.10 +/- 2.5-102.47 +/- 2.94 (CLS) and 99.12 +/- 1.71-100.92 +/- 1.54
      (PCR) for lamivudine and 96.00 +/- 2.94-98.17 +/- 1.72 (CLS) and 97.40 +/- 1.55
      97.80 +/- 1.92 (PCR) for stavudine, respectively. Good percentage recoveries and
      proper statistical data obtained with both the laboratory prepared mixtures and
      the commercial tablets proved the suitability and efficiency of the proposed
      procedures for routine analysis and quality control purposes with quite
      satisfactory precision. A comparison of the obtained results from CLS and PCR
      were also performed with those obtained from reported method. The obtained F- and
      t-values obtained indicating no significant differences between the results of
      the proposed and reported methods. 

PMID- 24109203
TI  - Synthesis and antihistaminic activity of 3H-benzo [4,5] thieno [2,3-d][1,2,3]
      triazin-4-ones.
AB  - In the present study the antihistaminic activity of tricyclic benzothieno 1,2,3
      triazine derivatives namely CP-3 (3-(phenyl)-5,6,7,8-tetrahydro,3H-benzo[4,5]
      thieno [2,3-d][1,2,3] triazin-4-one), CP-5 (3-(3-methyl phenyl)-5,6,7,8
      tetrahydro,3H-benzo[4,5] thieno [2,3-d][1,2,3] triazin-4-one) and CP-8 (3-(4
      chloro phenyl)-5,6,7,8-tetrahydro,3H-benzo[4,5] thieno [2,3-d][1,2,3] triazin-4
      one) were evaluated using in vitro (isolated guinea pig ileum) and in vivo
      (bronchodilator activity in guinea pigs) models and the sedative potential of the
      test compounds were evaluated using actophotometer in mice. In in vitro
      antihistaminic study, the CP-3, CP-5, CP-8 and chlorpheniramine maleate (CPM)
      have shown a rightward shift in concentration response curve (CRC) of histamine
      with a change in EC50 values of histamine in all the four tissue preparations.
      The slope obtained in the schild plot indicated that CP-5, CP-8 and CPM were
      competitive in nature for H1-receptors. However, CP-3 has shown non-competitive
      antagonism. In in vivo antihistaminic study, the CP-3, CP-5, CP-8 and CPM have
      shown mean increase in exposition time against histamine challenge compared to
      control group (p < 0.001). All the test drugs (10 mg/kg) and CPM (2 mg/kg) have
      offered a significant (p < 0.001) protection against preconvulsive dyspnoea (PCD)
      compared to control. In conclusion, all the test drugs have shown very good
      antihistaminic activity and the test drugs have very little sedative action
      compared to CPM. 

PMID- 24109201
TI  - Obstructive sleep apnea in children: a critical update.
AB  - Obstructive sleep apnea (OSA) in children is a highly prevalent disorder caused
      by a conglomeration of complex pathophysiological processes, leading to recurrent
      upper airway dysfunction during sleep. The clinical relevance of OSA resides in
      its association with significant morbidities that affect the cardiovascular,
      neurocognitive, and metabolic systems. The American Academy of Pediatrics
      recently reiterated its recommendations that children with symptoms and signs
      suggestive of OSA should be investigated with polysomnography (PSG), and treated
      accordingly. However, treatment decisions should not only be guided by PSG
      results, but should also integrate the magnitude of symptoms and the presence or
      absence of risk factors and signs of OSA morbidity. The first-line therapy in
      children with adenotonsillar hypertrophy is adenotonsillectomy, although there is
      increasing evidence that medical therapy, in the form of intranasal steroids or
      montelukast, may be considered in mild OSA. In this review, we delineate the
      major concepts regarding the pathophysiology of OSA, its morbidity, diagnosis,
      and treatment. 

PMID- 24109204
TI  - Transfer of drug dissolution testing by statistical approaches: Case study.
AB  - The analytical transfer is a complete process that consists in transferring an
      analytical procedure from a sending laboratory to a receiving laboratory. After
      having experimentally demonstrated that also masters the procedure in order to
      avoid problems in the future. Method of transfers is now commonplace during the
      life cycle of analytical method in the pharmaceutical industry. No official
      guideline exists for a transfer methodology in pharmaceutical analysis and the
      regulatory word of transfer is more ambiguous than for validation. Therefore, in
      this study, Gauge repeatability and reproducibility (R&R) studies associated with
      other multivariate statistics appropriates were successfully applied for the
      transfer of the dissolution test of diclofenac sodium as a case study from a
      sending laboratory A (accredited laboratory) to a receiving laboratory B. The
      HPLC method for the determination of the percent release of diclofenac sodium in
      solid pharmaceutical forms (one is the discovered product and another generic)
      was validated using accuracy profile (total error) in the sender laboratory A.
      The results showed that the receiver laboratory B masters the test dissolution
      process, using the same HPLC analytical procedure developed in laboratory A. In
      conclusion, if the sender used the total error to validate its analytical method,
      dissolution test can be successfully transferred without mastering the analytical
      method validation by receiving laboratory B and the pharmaceutical analysis
      method state should be maintained to ensure the same reliable results in the
      receiving laboratory. 

PMID- 24109205
TI  - Design of a novel bilayered gastric mucoadhesive system for localized and
      unidirectional release of lamotrigine.
AB  - Lamotrigine is a BCS class II drug with pH dependent solubility. The bilayered
      gastric mucoadhesive tablets of lamotrigine were designed such that the drug and
      controlled release polymers were incorporated in the upper layer and the lower
      layer had the mucoadhesive polymers. The major ingredients selected for the upper
      layer were the drug and control release polymer (either HPMC K15M or polyox)
      while the lower MA layer predominantly comprised of Carbopol 974P. A 2(3) full
      factorial design was constructed for this study and the tablets were optimized
      for parameters like tablet size, shape, ex vivo mucoadhesive properties and
      unidirectional drug release. Oval tablets with an average size of 14 mm diameter
      were set optimum. Maximum mucoadhesive bond strength of 79.3 +/- 0.91 * 10(3)
      dyn/cm(2) was achieved with carbopol when used in combination with a synergistic
      resin polymer. All the tested formulations presented a mucoadhesion time of
      greater than 12 h. The incorporation of methacrylic polymers in the lower layer
      ensured unidirectional drug release from the bilayered tablets. The
      unidirectional drug release was confirmed after comparing the dissolution results
      of paddle method with those of a modified basket method. Model independent
      similarity and dissimilarity factor methods were used for the comparison of
      dissolution results. Controlled drug release profiles with zero order kinetics
      were obtained with polyox and HPMC K15M which reported t 90% at 6th and 12th
      hours, respectively. The "n" value with polyox was 0.992 and that with HPMC K15M
      was 0.946 indicating an approximate case II transport. These two formulations
      showed the potential for oral administration of lamotrigine as bilayered gastric
      mucoadhesive tablets by yielding highest similarity factor values, 96.06 and
      92.47, respectively, between the paddle and modified basket method dissolution
      release profiles apart from reporting the best tablet physical properties and
      maximum mucoadhesive strength. 

PMID- 24109206
TI  - Physicochemical characterization and in vitro dissolution studies of solid
      dispersions of ketoprofen with PVP K30 and d-mannitol.
AB  - Aim of the present study was to improve the solubility and dissolution rate of
      poorly water soluble, BCS class-II drug Ketoprofen (KETO) by solid-dispersion
      approach. Solid dispersions were prepared by using polyvinylpyrrolidone K30 (PVP
      K30) and d-mannitol in different drugs to carrier ratios. Dispersions with PVP
      K30 were prepared by kneading and solvent evaporation techniques, whereas solid
      dispersions containing d-mannitol were prepared by kneading and melting
      techniques. These formulations were characterized in the liquid state by phase
      solubility studies and in the solid state by Differential Scanning Calorimetry
      (DSC), Fourier Transform Infrared (FTIR) spectroscopy, X-ray diffraction (XRD)
      and Scanning Electron Microscopy (SEM). The aqueous solubility of KETO was
      favored by the presence of both carriers. The negative values of Gibbs free
      energy illustrate the spontaneous transfer from pure water to the aqueous polymer
      environment. Solid state characterization indicated KETO was present as fine
      particles in d-mannitol solid dispersions and entrapped in carrier matrix of PVP
      K30 solid dispersions. In contrast to the very slow dissolution rate of pure
      KETO, dispersions of drug in carriers considerably improved the dissolution rate.
      This can be attributed to increased wettability and dispersibility, as well as
      decreased crystallinity and increase in amorphous fraction of drug. Solid
      dispersions prepared with PVP K30 showed the highest improvement in dissolution
      rate of KETO. Even physical mixtures of KETO prepared with both carriers also
      showed better dissolution profiles than those of pure KETO. 

PMID- 24109207
TI  - Stability switches of arbitrary high-order consensus in multiagent networks with
      time delays.
AB  - High-order consensus seeking, in which individual high-order dynamic agents share
      a consistent view of the objectives and the world in a distributed manner, finds
      its potential broad applications in the field of cooperative control. This paper
      presents stability switches analysis of arbitrary high-order consensus in
      multiagent networks with time delays. By employing a frequency domain method, we
      explicitly derive analytical equations that clarify a rigorous connection between
      the stability of general high-order consensus and the system parameters such as
      the network topology, communication time-delays, and feedback gains.
      Particularly, our results provide a general and a fairly precise notion of how
      increasing communication time-delay causes the stability switches of consensus.
      Furthermore, under communication constraints, the stability and robustness
      problems of consensus algorithms up to third order are discussed in details to
      illustrate our central results. Numerical examples and simulation results for
      fourth-order consensus are provided to demonstrate the effectiveness of our
      theoretical results. 

PMID- 24109208
TI  - A comparison of ice cold water pretreatment and alpha-bromonaphthalene
      cytogenetic method for identification of Papaver species.
AB  - The plants belonging to many species in genus Papaver are very similar and have
      very small chromosomes that make identification very difficult. The study aimed
      to compare the effects of alpha-bromonaphtalene and ice cold water pretreatment
      to identify chromosomes of Papaver species collected from different areas of
      Iranian West Azerbaijan and Turkish Van, Agri and, Hakkari provinces. The seeds
      were germinated in Jacobson trays at 24 degrees C under continuous light.
      Thereafter, roots from 1.5 cm long plantlets were pretreated with alpha
      bromonaphtalene for 15, 30, and 45 min or at 0 degrees C in ice cold water for 24
      h before fixing, hydrolyzation, and feulgen staining. The ice cold water
      pretreatment was more appropriate and easy to determine chromosomes. Seeds from
      seven samples did not germinate. Sixty samples out of the rest of 62 samples were
      identified as P. pseudo orientale, one sample was identified as P. bracteatum,
      and another as P. orientale. This is the first study that used ice cold water to
      determine the chromosomes in papaver species. It is hoped that it will also
      facilitate to determine chromosome number and identify other papver species.

PMID- 24109209
TI  - Comparative analyses of response surface methodology and artificial neural
      network on medium optimization for Tetraselmis sp. FTC209 grown under mixotrophic
      condition.
AB  - Mixotrophic metabolism was evaluated as an option to augment the growth and lipid
      production of marine microalga Tetraselmis sp. FTC 209. In this study, a five
      level three-factor central composite design (CCD) was implemented in order to
      enrich the W-30 algal growth medium. Response surface methodology (RSM) was
      employed to model the effect of three medium variables, that is, glucose (organic
      C source), NaNO3 (primary N source), and yeast extract (supplementary N, amino
      acids, and vitamins) on biomass concentration, X(max), and lipid yield,
      P(max)/X(max). RSM capability was also weighed against an artificial neural
      network (ANN) approach for predicting a composition that would result in maximum
      lipid productivity, Pr(lipid). A quadratic regression from RSM and a Levenberg
      Marquardt trained ANN network composed of 10 hidden neurons eventually produced
      comparable results, albeit ANN formulation was observed to yield higher values of
      response outputs. Finalized glucose (24.05 g/L), NaNO3 (4.70 g/L), and yeast
      extract (0.93 g/L) concentration, affected an increase of X(max) to 12.38 g/L and
      lipid a accumulation of 195.77 mg/g dcw. This contributed to a lipid productivity
      of 173.11 mg/L per day in the course of two-week cultivation.

PMID- 24109210
TI  - Activation of the endoplasmic reticulum calcium sensor STIM1 and store-operated
      calcium entry by rotavirus requires NSP4 viroporin activity.
AB  - Rotavirus nonstructural protein 4 (NSP4) induces dramatic changes in cellular
      calcium homeostasis. These include increased endoplasmic reticulum (ER)
      permeability, resulting in decreased ER calcium stores and activation of plasma
      membrane (PM) calcium influx channels, ultimately causing a 2- to 4-fold
      elevation in cytoplasmic calcium. Elevated cytoplasmic calcium is absolutely
      required for virus replication, but the underlying mechanisms responsible for
      calcium influx remain poorly understood. NSP4 is an ER-localized viroporin, whose
      activity depletes ER calcium, which ultimately leads to calcium influx. We
      hypothesized that NSP4-mediated depletion of ER calcium activates store-operated
      calcium entry (SOCE) through activation of the ER calcium sensor stromal
      interaction molecule 1 (STIM1). We established and used a stable yellow
      fluorescent protein-expressing STIM1 cell line (YFP-STIM1) as a biosensor to
      assess STIM1 activation (puncta formation) by rotavirus infection and NSP4
      expression. We found that STIM1 is constitutively active in rotavirus-infected
      cells and that STIM1 puncta colocalize with the PM-localized Orai1 SOCE calcium
      channel. Expression of wild-type NSP4 activated STIM1, resulting in PM calcium
      influx, but an NSP4 viroporin mutant failed to induce STIM1 activation and did
      not activate the PM calcium entry pathway. Finally, knockdown of STIM1
      significantly reduced rotavirus yield, indicating STIM1 plays a critical role in
      virus replication. These data demonstrate that while rotavirus may ultimately
      activate multiple calcium channels in the PM, calcium influx is predicated on
      NSP4 viroporin-mediated activation of STIM1 in the ER. This is the first report
      of viroporin-mediated activation of SOCE, reinforcing NSP4 as a robust model to
      understand dysregulation of calcium homeostasis during virus infections. 

PMID- 24109211
TI  - The nuclear-cytoplasmic shuttling of virion host shutoff RNase is enabled by
      pUL47 and an embedded nuclear export signal and defines the sites of degradation
      of AU-rich and stable cellular mRNAs.
AB  - The herpes simplex virus host shutoff RNase (VHS-RNase) is the major early block
      of host responses to infection. VHS-RNase is introduced into cells during
      infection and selectively degrades stable mRNAs made before infection and the
      normally short-lived AU-rich stress response mRNAs induced by sensors of innate
      immunity. Through its interactions with pUL47, another tegument protein, it
      spares from degradation viral mRNAs. Analyses of embedded motifs revealed that
      VHS-RNase contains a nuclear export signal (NES) but not a nuclear localization
      signal. To reconcile the potential nuclear localization with earlier studies
      showing that VHS-RNase degrades mRNAs in polyribosomes, we constructed a mutant
      in which NES was ablated. Comparison of the mutant and wild-type VHS-RNases
      revealed the following. (i) On infection, VHS-RNase is transported to the
      nucleus, but only the wild-type protein shuttles between the nucleus and
      cytoplasm. (ii) Both VHS-RNases localized in the cytoplasm following
      transfection. On cotransfection with pUL47, a fraction of VHS-RNase was
      translocated to the nucleus, suggesting that pUL47 may enable nuclear
      localization of VHS-RNase. (iii) In infected cells, VHS-RNase lacking NES
      degraded the short-lived AU-rich mRNAs but not the stable mRNAs. In transfected
      cells, both wild-type and NES mutant VHS-RNases effectively degraded cellular
      mRNAs. Our results suggest that the stable mRNAs are degraded in the cytoplasm,
      whereas the AU-rich mRNAs may be degraded in both cellular compartments. The
      selective sparing of viral mRNAs may take place during the nuclear phase in the
      course of interaction of pUL47, VHS-RNase, and nascent viral mRNAs. 

PMID- 24109212
TI  - Truncation and sequence shuffling of segment 6 generate replication-competent
      neuraminidase-negative influenza H5N1 viruses.
AB  - Influenza viruses are highly genetically variable and escape from immunogenic
      pressure by antigenic changes in their surface proteins, referred to as
      "antigenic drift" and "antigenic shift." To assess the potential genetic
      plasticity under strong selection pressure, highly pathogenic avian influenza
      virus (HPAIV) of subtype H5N1 was passaged 50 times in embryonated chicken eggs
      in the presence of a neutralizing, polyclonal chicken serum. The resulting mutant
      acquired major alterations in the neuraminidase (NA)-encoding segment. Extensive
      deletions and rearrangements were detected, in contrast to only 12 amino acid
      substitutions within all other segments. Interestingly, this new neuraminidase
      segment resulted from complex sequence shuffling and insertion of a short
      fragment originating from the PA segment. Characterization of that novel variant
      revealed a loss of the neuraminidase protein and enzymatic activity, but its
      replication efficiency remained comparable to that of the wild type. Using
      reverse genetics, a recombinant virus consisting of the wild-type backbone and
      the shortened NA segment could be generated; however, generation of this
      recombinant virus required the polybasic hemagglutinin cleavage site. Two
      independent repetitions starting with egg passage 30 in the presence of
      alternative chicken-derived immune sera selected mutants with similar but
      different large deletions within the NA segment without any neuraminidase
      activity, indicating a general mechanism. In chicken, these virus variants were
      avirulent, even though the HPAIV polybasic hemagglutinin cleavage site was still
      present. Overall, the variants reported here are the first HPAIV H5N1 strains
      without a functional neuraminidase shown to grow efficiently without any helper
      factor. These novel HPAIV variants may facilitate future studies shedding light
      on the role of neuraminidase in virus replication and pathogenicity. 

PMID- 24109213
TI  - Contributions of herpes simplex virus 1 envelope proteins to entry by
      endocytosis.
AB  - Herpes simplex virus (HSV) proteins specifically required for endocytic entry but
      not direct penetration have not been identified. HSVs deleted of gE, gG, gI, gJ,
      gM, UL45, or Us9 entered cells via either pH-dependent or pH-independent
      endocytosis and were inactivated by mildly acidic pH. Thus, the required HSV
      glycoproteins, gB, gD, and gH-gL, may be sufficient for entry regardless of entry
      route taken. This may be distinct from entry mechanisms employed by other human
      herpesviruses.

PMID- 24109214
TI  - Simian foamy virus infection of rhesus macaques in Bangladesh: relationship of
      latent proviruses and transcriptionally active viruses.
AB  - Simian foamy viruses (SFV) are complex retroviruses that are ubiquitous in
      nonhuman primates (NHP) and are zoonotically transmitted to humans, presumably
      through NHP saliva, by licking, biting, and other behaviors. We have studied SFV
      in free-ranging rhesus macaques in Bangladesh. It has been previously shown that
      SFV in immunocompetent animals replicates to detectable levels only in
      superficial epithelial cells of the oral mucosa, although latent proviruses are
      found in most, if not all, tissues. In this study, we compare DNA sequences from
      latent SFV proviruses found in blood cells of 30 Bangladesh rhesus macaques to
      RNA sequences of transcriptionally active SFV from buccal swabs obtained from the
      same animals. Viral strains, defined by differences in SFV gag sequences, from
      buccal mucosal specimens overlapped with those from blood samples in 90% of
      animals. Thus, latent proviruses in peripheral blood mononuclear cells (PBMC)
      are, to a great extent, representative of viruses likely to be transmitted to
      other hosts. The level of SFV RNA in buccal swabs varied greatly between
      macaques, with increasing amounts of viral RNA in older animals. Evidence of
      APOBEC3-induced mutations was found in gag sequences derived from the blood and
      oral mucosa. 

PMID- 24109215
TI  - Sequence and functional analysis of the envelope glycoproteins of hepatitis C
      virus variants selectively transmitted to a new host.
AB  - Hepatitis C virus (HCV) remains a challenging public health problem worldwide.
      The identification of viral variants establishing de novo infections and
      definition of the phenotypic requirements for transmission would facilitate the
      design of preventive strategies. We explored the transmission of HCV variants in
      three cases of acute hepatitis following needlestick accidents. We used single
      genome amplification of glycoprotein E1E2 gene sequences to map the genetic
      bottleneck upon transmission accurately. We found that infection was likely
      established by a single variant in two cases and six variants in the third case.
      Studies of donor samples showed that the transmitted variant E1E2 amino acid
      sequences were identical or closely related to those of variants from the donor
      virus populations. The transmitted variants harbored a common signature site at
      position 394, within hypervariable region 1 of E2, together with additional
      signature amino acids specific to each transmission pair. Surprisingly, these
      E1E2 variants conferred no greater capacity for entry than the E1E2 derived from
      nontransmitted variants in lentiviral pseudoparticle assays. Mutants escaping the
      antibodies of donor sera did not predominate among the transmitted variants
      either. The fitness parameters affecting the selective outgrowth of HCV variants
      after transmission in an immunocompetent host may thus be more complex than those
      suggested by mouse models. Human antibodies directed against HCV envelope
      effectively cross-neutralized the lentiviral particles bearing E1E2 derived from
      transmitted variants. These findings provide insight into the molecular
      mechanisms underlying HCV transmission and suggest that viral entry is a
      potential target for the prevention of HCV infection. 

PMID- 24109216
TI  - Effect of multimerization on membrane association of Rous sarcoma virus and HIV-1
      matrix domain proteins.
AB  - In most retroviruses, plasma membrane (PM) association of the Gag structural
      protein is a critical step in viral assembly, relying in part on interaction
      between the highly basic Gag MA domain and the negatively charged inner leaflet
      of the PM. Assembly is thought to begin with Gag dimerization followed by
      multimerization, resulting in a hexameric lattice. To directly address the role
      of multimerization in membrane binding, we fused the MA domains of Rous sarcoma
      virus (RSV) and HIV-1 to the chemically inducible dimerization domain FK506
      binding protein (FKBP) or to the hexameric protein CcmK4 from cyanobacteria. The
      cellular localization of the resulting green fluorescent protein (GFP)-tagged
      chimeric proteins was examined by fluorescence imaging, and the association of
      the proteins with liposomes was quantified by flotation in sucrose gradients,
      following synthesis in a reticulocyte extract or as purified proteins. Four lipid
      compositions were tested, representative of liposomes commonly reported in
      flotation experiments. By themselves, GFP-tagged RSV and HIV-1 MA proteins were
      largely cytoplasmic, but both hexamerized proteins were highly concentrated at
      the PM. Dimerization led to partial PM localization for HIV-1 MA. These in vivo
      effects of multimerization were reproduced in vitro. In flotation analyses, the
      intact RSV and HIV-1 Gag proteins were more similar to multimerized MA than to
      monomeric MA. RNA is reported to compete with acidic liposomes for HIV-1 Gag
      binding, and thus we also examined the effects of RNase treatment or tRNA
      addition on flotation. tRNA competed with liposomes in the case of some but not
      all lipid compositions and ionic strengths. Taken together, our results further
      underpin the model that multimerization is critical for PM association of
      retroviral Gag proteins. In addition, they suggest that the modulation of
      membrane binding by RNA, as previously reported for HIV-1, may not hold for RSV. 

PMID- 24109217
TI  - A two-pronged structural analysis of retroviral maturation indicates that core
      formation proceeds by a disassembly-reassembly pathway rather than a displacive
      transition.
AB  - Retrovirus maturation involves sequential cleavages of the Gag polyprotein,
      initially arrayed in a spherical shell, leading to formation of capsids with
      polyhedral or conical morphology. Evidence suggests that capsids assemble de novo
      inside maturing virions from dissociated capsid (CA) protein, but the possibility
      persists of a displacive pathway in which the CA shell remains assembled but is
      remodeled. Inhibition of the final cleavage between CA and spacer peptide SP1/SP
      blocks the production of mature capsids. We investigated whether retention of SP
      might render CA assembly incompetent by testing the ability of Rous sarcoma virus
      (RSV) CA-SP to assemble in vitro into icosahedral capsids. Capsids were indeed
      assembled and were indistinguishable from those formed by CA alone, indicating
      that SP was disordered. We also used cryo-electron tomography to characterize HIV
      1 particles produced in the presence of maturation inhibitor PF-46396 or with the
      cleavage-blocking CA5 mutation. Inhibitor-treated virions have a shell that
      resembles the CA layer of the immature Gag shell but is less complete. Some CA
      protein is generated but usually not enough for a mature core to assemble. We
      propose that inhibitors like PF-46396 bind to the Gag lattice where they deny the
      protease access to the CA-SP1 cleavage site and prevent the release of CA. CA5
      particles, which exhibit no cleavage at the CA-SP1 site, have spheroidal shells
      with relatively thin walls. It appears that this lattice progresses displacively
      toward a mature-like state but produces neither conical cores nor infectious
      virions. These observations support the disassembly-reassembly pathway for core
      formation. 

PMID- 24109218
TI  - Next-generation sequence analysis of the genome of RFHVMn, the macaque homolog of
      Kaposi's sarcoma (KS)-associated herpesvirus, from a KS-like tumor of a pig
      tailed macaque.
AB  - The complete sequence of retroperitoneal fibromatosis-associated herpesvirus
      Macaca nemestrina (RFHVMn), the pig-tailed macaque homolog of Kaposi's sarcoma
      associated herpesvirus (KSHV), was determined by next-generation sequence
      analysis of a Kaposi's sarcoma (KS)-like macaque tumor. Colinearity of genes was
      observed with the KSHV genome, and the core herpesvirus genes had strong sequence
      homology to the corresponding KSHV genes. RFHVMn lacked homologs of open reading
      frame 11 (ORF11) and KSHV ORFs K5 and K6, which appear to have been generated by
      duplication of ORFs K3 and K4 after the divergence of KSHV and RFHV. RFHVMn
      contained positional homologs of all other unique KSHV genes, although some
      showed limited sequence similarity. RFHVMn contained a number of candidate
      microRNA genes. Although there was little sequence similarity with KSHV
      microRNAs, one candidate contained the same seed sequence as the positional
      homolog, kshv-miR-K12-10a, suggesting functional overlap. RNA transcript splicing
      was highly conserved between RFHVMn and KSHV, and strong sequence conservation
      was noted in specific promoters and putative origins of replication, predicting
      important functional similarities. Sequence comparisons indicated that RFHVMn and
      KSHV developed in long-term synchrony with the evolution of their hosts, and both
      viruses phylogenetically group within the RV1 lineage of Old World primate
      rhadinoviruses. RFHVMn is the closest homolog of KSHV to be completely sequenced
      and the first sequenced RV1 rhadinovirus homolog of KSHV from a nonhuman Old
      World primate. The strong genetic and sequence similarity between RFHVMn and
      KSHV, coupled with similarities in biology and pathology, demonstrate that RFHVMn
      infection in macaques offers an important and relevant model for the study of
      KSHV in humans. 

PMID- 24109219
TI  - Tetherin upregulation in simian immunodeficiency virus-infected macaques.
AB  - Here we show that simian immunodeficiency virus (SIV) infection of rhesus
      macaques results in rapid upregulation of tetherin (BST-2 or CD317) on peripheral
      blood lymphocytes, including the CD4(+) CCR5(+) T cell targets of virus
      infection, with a peak of induction that coincides with peak alpha interferon
      (IFN-alpha) levels in plasma, and that tetherin remains above baseline levels
      throughout chronic infection. These observations are consistent with a role for
      tetherin in innate immunity to immunodeficiency virus infection. 

PMID- 24109220
TI  - HSP90 protects the human T-cell leukemia virus type 1 (HTLV-1) tax oncoprotein
      from proteasomal degradation to support NF-kappaB activation and HTLV-1
      replication.
AB  - Human T-cell leukemia virus type 1 (HTLV-1) is the causative agent of adult T
      cell leukemia (ATL) and HTLV-1-associated myelopathy/tropical spastic paraparesis
      (HAM/TSP). The HTLV-1 genome encodes the Tax protein that plays essential
      regulatory roles in HTLV-1 replication and oncogenic transformation of T
      lymphocytes. Despite intensive study of Tax, how Tax interfaces with host
      signaling pathways to regulate virus replication and drive T-cell proliferation
      and immortalization remains poorly understood. To gain new insight into the
      mechanisms of Tax function and regulation, we used tandem affinity purification
      and mass spectrometry to identify novel cellular Tax-interacting proteins. This
      screen identified heat shock protein 90 (HSP90) as a new binding partner of Tax.
      The interaction between HSP90 and Tax was validated by coimmunoprecipitation
      assays, and colocalization between the two proteins was observed by confocal
      microscopy. Treatment of HTLV-1-transformed cells with the HSP90 inhibitor 17
      DMAG elicited proteasomal degradation of Tax in the nuclear matrix with
      concomitant inhibition of NF-kappaB and HTLV-1 long terminal repeat (LTR)
      activation. Knockdown of HSP90 by lentiviral shRNAs similarly provoked a loss of
      Tax protein in HTLV-1-transformed cells. Finally, treatment of HTLV-1-transformed
      cell lines with 17-DMAG suppressed HTLV-1 replication and promoted apoptotic cell
      death. Taken together, our results reveal that Tax is a novel HSP90 client
      protein and HSP90 inhibitors may exert therapeutic benefits for ATL and HAM/TSP
      patients. 

PMID- 24109222
TI  - Reversible inactivation and desiccation tolerance of silicified viruses.
AB  - Long-distance host-independent virus dispersal is poorly understood, especially
      for viruses found in isolated ecosystems. To demonstrate a possible dispersal
      mechanism, we show that bacteriophage T4, archaeal virus Sulfolobus spindle
      shaped virus Kamchatka, and vaccinia virus are reversibly inactivated by
      mineralization in silica under conditions similar to volcanic hot springs. In
      contrast, bacteriophage PRD1 is not silicified. Moreover, silicification provides
      viruses with remarkable desiccation resistance, which could allow extensive
      aerial dispersal. 

PMID- 24109221
TI  - Standard trivalent influenza virus protein vaccination does not prime antibody
      dependent cellular cytotoxicity in macaques.
AB  - Yearly vaccination with the trivalent inactivated influenza vaccine (TIV) is
      recommended, since current vaccines induce little cross neutralization to
      divergent influenza strains. Whether the TIV can induce antibody-dependent
      cellular cytotoxicity (ADCC) responses that can cross-recognize divergent
      influenza virus strains is unknown. We immunized 6 influenza-naive pigtail
      macaques twice with the 2011-2012 season TIV and then challenged the macaques,
      along with 12 control macaques, serially with H1N1 and H3N2 viruses. We measured
      ADCC responses in plasma to a panel of H1 and H3 hemagglutinin (HA) proteins and
      influenza virus-specific CD8 T cell (CTL) responses using a sensitive major
      histocompatibility complex (MHC) tetramer reagent. The TIV was weakly immunogenic
      and, although binding antibodies were detected by enzyme-linked immunosorbent
      assay (ELISA), did not induce detectable influenza virus-specific ADCC or CTL
      responses. The H1N1 challenge elicited robust ADCC to both homologous and
      heterologous H1 HA proteins, but not influenza virus HA proteins from different
      subtypes (H2 to H7). There was no anamnestic influenza virus-specific ADCC or CTL
      response in vaccinated animals. The subsequent H3N2 challenge did not induce or
      boost ADCC either to H1 HA proteins or to divergent H3 proteins but did boost CTL
      responses. ADCC or CTL responses were not induced by TIV vaccination in influenza
      naive macaques. There was a marked difference in the ability of infection
      compared to that of vaccination to induce cross-reactive ADCC and CTL responses.
      Improved vaccination strategies are needed to induce broad-based ADCC immunity to
      influenza. 

PMID- 24109223
TI  - A chimeric dengue virus vaccine using Japanese encephalitis virus vaccine strain
      SA14-14-2 as backbone is immunogenic and protective against either parental virus
      in mice and nonhuman primates.
AB  - The development of a safe and efficient dengue vaccine represents a global
      challenge in public health. Chimeric dengue viruses (DENV) based on an attenuated
      flavivirus have been well developed as vaccine candidates by using reverse
      genetics. In this study, based on the full-length infectious cDNA clone of the
      well-known Japanese encephalitis virus live vaccine strain SA14-14-2 as a
      backbone, a novel chimeric dengue virus (named ChinDENV) was rationally designed
      and constructed by replacement with the premembrane and envelope genes of dengue
      2 virus. The recovered chimeric virus showed growth and plaque properties similar
      to those of the parental DENV in mammalian and mosquito cells. ChinDENV was
      highly attenuated in mice, and no viremia was induced in rhesus monkeys upon
      subcutaneous inoculation. ChinDENV retained its genetic stability and attenuation
      phenotype after serial 15 passages in cultured cells. A single immunization with
      various doses of ChinDENV elicited strong neutralizing antibodies in a dose
      dependent manner. When vaccinated monkeys were challenged with wild-type DENV,
      all animals except one that received the lower dose were protected against the
      development of viremia. Furthermore, immunization with ChinDENV conferred
      efficient cross protection against lethal JEV challenge in mice in association
      with robust cellular immunity induced by the replicating nonstructural proteins.
      Taken together, the results of this preclinical study well demonstrate the great
      potential of ChinDENV for further development as a dengue vaccine candidate, and
      this kind of chimeric flavivirus based on JE vaccine virus represents a powerful
      tool to deliver foreign antigens. 

PMID- 24109224
TI  - The Fc region of an antibody impacts the neutralization of West Nile viruses in
      different maturation states.
AB  - Flavivirus-infected cells secrete a structurally heterogeneous population of
      viruses because of an inefficient virion maturation process. Flaviviruses
      assemble as noninfectious, immature virions composed of trimers of envelope (E)
      and precursor membrane (prM) protein heterodimers. Cleavage of prM is a required
      process during virion maturation, although this often remains incomplete for
      infectious virus particles. Previous work demonstrated that the efficiency of
      virion maturation could impact antibody neutralization through changes in the
      accessibility of otherwise cryptic epitopes on the virion. In this study, we show
      that the neutralization potency of monoclonal antibody (MAb) E33 is sensitive to
      the maturation state of West Nile virus (WNV), despite its recognition of an
      accessible epitope, the domain III lateral ridge (DIII-LR). Comprehensive epitope
      mapping studies with 166 E protein DIII-LR variants revealed that the functional
      footprint of MAb E33 on the E protein differs subtly from that of the well
      characterized DIII-LR MAb E16. Remarkably, aromatic substitutions at E protein
      residue 306 ablated the maturation state sensitivity of E33 IgG, and the
      neutralization efficacy of E33 Fab fragments was not affected by changes in the
      virion maturation state. We propose that E33 IgG binding on mature virions
      orients the Fc region in a manner that impacts subsequent antibody binding to
      nearby sites. This Fc-mediated steric constraint is a novel mechanism by which
      the maturation state of a virion modulates the efficacy of the humoral immune
      response to flavivirus infection. 

PMID- 24109225
TI  - Measles virus fusion machinery activated by sialic acid binding globular domain.
AB  - Paramyxoviruses, including the human pathogen measles virus (MV) and the avian
      Newcastle disease virus (NDV), enter host cells through fusion of the viral
      envelope with the target cell membrane. This fusion is driven by the concerted
      action of two viral envelope glycoproteins: the receptor binding protein and the
      fusion protein (F). The MV receptor binding protein (hemagglutinin [H]) attaches
      to proteinaceous receptors on host cells, while the receptor binding protein of
      NDV (hemagglutinin-neuraminidase [HN]) interacts with sialic acid-containing
      receptors. The receptor-bound HN/H triggers F to undergo conformational changes
      that render it competent to mediate fusion of the viral and cellular membranes.
      The mechanism of fusion activation has been proposed to be different for sialic
      acid-binding viruses and proteinaceous receptor-binding viruses. We report that a
      chimeric protein containing the NDV HN receptor binding region and the MV H stalk
      domain can activate MV F to fuse, suggesting that the signal to the stalk of a
      protein-binding receptor binding molecule can be transmitted from a sialic acid
      binding domain. By engineering the NDV HN globular domain to interact with a
      proteinaceous receptor, the fusion activation signal was preserved. Our findings
      are consistent with a unified mechanism of fusion activation, at least for the
      Paramyxovirinae subfamily, in which the receptor binding domains of the receptor
      binding proteins are interchangeable and the stalk determines the specificity of
      F activation. 

PMID- 24109226
TI  - Evolution of a self-inducible cytolethal distending toxin type V-encoding
      bacteriophage from Escherichia coli O157:H7 to Shigella sonnei.
AB  - Some cdt genes are located within the genome of inducible or cryptic
      bacteriophages, but there is little information about the mechanisms of cdt
      transfer because of the reduced number of inducible Cdt phages described. In this
      study, a new self-inducible Myoviridae Cdt phage (PhiAA91) was isolated from a
      nonclinical O157:H7 Shiga toxin-producing Escherichia coli strain and was used to
      lysogenize a cdt-negative strain of Shigella sonnei. We found that the phage
      induced from S. sonnei (PhiAA91-ss) was not identical to the original phage.
      PhiAA91-ss was used to infect a collection of 57 bacterial strains, was
      infectious in 59.6% of the strains, and was able to lysogenize 22.8% of them. The
      complete sequence of PhiAA91-ss showed a 33,628-bp genome with characteristics of
      a P2-like phage with the cdt operon located near the cosR site. We found an IS21
      element composed of two open reading frames inserted within the cox gene of the
      phage, causing gene truncation. Truncation of cox does not affect lytic induction
      but could contribute to phage recombination and generation of lysogens. The IS21
      element was not present in the PhiAA91 phage from E. coli, but it was
      incorporated into the phage genome after its transduction in Shigella. This study
      shows empirically the evolution of temperate bacteriophages carrying virulence
      genes after infecting a new host and the generation of a phage population with
      better lysogenic abilities that would ultimately lead to the emergence of new
      pathogenic strains. 

PMID- 24109227
TI  - Efficiency of cell-free and cell-associated virus in mucosal transmission of
      human immunodeficiency virus type 1 and simian immunodeficiency virus.
AB  - Effective strategies are needed to block mucosal transmission of human
      immunodeficiency virus type 1 (HIV-1). Here, we address a crucial question in HIV
      1 pathogenesis: whether infected donor mononuclear cells or cell-free virus plays
      the more important role in initiating mucosal infection by HIV-1. This
      distinction is critical, as effective strategies for blocking cell-free and cell
      associated virus transmission may be different. We describe a novel ex vivo model
      system that utilizes sealed human colonic mucosa explants and demonstrate in both
      the ex vivo model and in vivo using the rectal challenge model in rhesus monkeys
      that HIV-1-infected lymphocytes can transmit infection across the mucosa more
      efficiently than cell-free virus. These findings may have significant
      implications for our understanding of the pathogenesis of mucosal transmission of
      HIV-1 and for the development of strategies to prevent HIV-1 transmission. 

PMID- 24109228
TI  - Nonhuman transferrin receptor 1 is an efficient cell entry receptor for
      Ocozocoautla de Espinosa virus.
AB  - Ocozocoautla de Espinosa virus (OCEV) is a novel, uncultured arenavirus. We found
      that the OCEV glycoprotein mediates entry into grivet and bat cells through
      transferrin receptor 1 (TfR1) binding but that OCEV glycoprotein precursor (GPC)
      pseudotyped retroviruses poorly entered 53 human cancer cell lines.
      Interestingly, OCEV and Tacaribe virus could use bat, but not human, TfR1.
      Replacing three human TfR1 amino acids with their bat ortholog counterparts
      transformed human TfR1 into an efficient OCEV and Tacaribe virus receptor. 

PMID- 24109229
TI  - Polyomavirus large T antigen binds symmetrical repeats at the viral origin in an
      asymmetrical manner.
AB  - Polyomaviruses have repeating sequences at their origins of replication that bind
      the origin-binding domain of virus-encoded large T antigen. In murine
      polyomavirus, the central region of the origin contains four copies (P1 to P4) of
      the sequence G(A/G)GGC. They are arranged as a pair of inverted repeats with a 2
      bp overlap between the repeats at the center. In contrast to simian virus 40
      (SV40), where the repeats are nonoverlapping and all four repeats can be
      simultaneously occupied, the crystal structure of the four central murine
      polyomavirus sequence repeats in complex with the polyomavirus origin-binding
      domain reveals that only three of the four repeats (P1, P2, and P4) are occupied.
      Isothermal titration calorimetry confirms that the stoichiometry is the same in
      solution as in the crystal structure. Consistent with these results, mutation of
      the third repeat has little effect on DNA replication in vivo. Thus, the apparent
      2-fold symmetry within the DNA repeats is not carried over to the protein-DNA
      complex. Flanking sequences, such as the AT-rich region, are known to be
      important for DNA replication. When the orientation of the central region was
      reversed with respect to these flanking regions, the origin was still able to
      replicate and the P3 sequence (now located at the P2 position with respect to the
      flanking regions) was again dispensable. This highlights the critical importance
      of the precise sequence of the region containing the pentamers in replication. 

PMID- 24109230
TI  - Varicella-zoster virus glycoprotein I is essential for spread in dorsal root
      ganglia and facilitates axonal localization of structural virion components in
      neuronal cultures.
AB  - Neurons of the sensory ganglia are the major site of varicella-zoster virus (VZV)
      latency and may undergo productive infection during reactivation. Although the
      VZV glycoprotein E/glycoprotein I (gE/gI) complex is known to be critical for
      neurovirulence, few studies have assessed the roles of these proteins during
      infection of dorsal root ganglia (DRG) due to the high human specificity of the
      virus. Here, we show that the VZV glycoprotein I gene is an important neurotropic
      gene responsible for mediating the spread of virus in neuronal cultures and
      explanted DRG. Inoculation of differentiated SH-SY5Y neuronal cell cultures with
      a VZV gI gene deletion strain (VZV rOkaDeltagI) showed a large reduction in the
      percentage of cells infected and significantly smaller plaque sizes in a
      comparison with cultures infected with the parental strain (VZV rOka). In
      contrast, VZV rOkaDeltagI was not significantly attenuated in fibroblast
      cultures, demonstrating a cell type-specific role for VZV gI. Analysis of
      rOkaDeltagI protein localization by immunofluorescent staining revealed aberrant
      localization of viral glycoprotein and capsid proteins, with little or no
      staining present in the axons of differentiated SH-SY5Y cells infected with
      rOkaDeltagI, yet axonal vesicle trafficking was not impaired. Further studies
      utilizing explanted human DRG indicated that VZV gI is required for the spread of
      virus within DRG. These data demonstrate a role for VZV gI in the cell-to-cell
      spread of virus during productive replication in neuronal cells and a role in
      facilitating the access of virion components to axons. 

PMID- 24109231
TI  - CpG dinucleotide frequencies reveal the role of host methylation capabilities in
      parvovirus evolution.
AB  - Parvoviruses are rapidly evolving viruses that infect a wide range of hosts,
      including vertebrates and invertebrates. Extensive methylation of the parvovirus
      genome has been recently demonstrated. A global pattern of methylation of CpG
      dinucleotides is seen in vertebrate genomes, compared to "fractional" methylation
      patterns in invertebrate genomes. It remains unknown if the loss of CpG
      dinucleotides occurs in all viruses of a given DNA virus family that infect host
      species spanning across vertebrates and invertebrates. We investigated the link
      between the extent of CpG dinucleotide depletion among autonomous parvoviruses
      and the evolutionary lineage of the infected host. We demonstrate major
      differences in the relative abundance of CpG dinucleotides among autonomous
      parvoviruses which share similar genome organization and common ancestry,
      depending on the infected host species. Parvoviruses infecting vertebrate hosts
      had significantly lower relative abundance of CpG dinucleotides than parvoviruses
      infecting invertebrate hosts. The strong correlation of CpG dinucleotide
      depletion with the gain in TpG/CpA dinucleotides and the loss of TpA
      dinucleotides among parvoviruses suggests a major role for CpG methylation in the
      evolution of parvoviruses. Our data present evidence that links the relative
      abundance of CpG dinucleotides in parvoviruses to the methylation capabilities of
      the infected host. In sum, our findings support a novel perspective of host
      driven evolution among autonomous parvoviruses. 

PMID- 24109232
TI  - Epstein-Barr virus latent membrane protein 2 effects on epithelial acinus
      development reveal distinct requirements for the PY and YEEA motifs.
AB  - Epstein-Barr virus (EBV) is a gammaherpesvirus associated with numerous cancers,
      including the epithelial cancers nasopharyngeal carcinoma (NPC) and gastric
      carcinoma. The latent membrane protein 2 (LMP2) encoded by EBV is consistently
      detected in NPC tumors and promotes a malignant phenotype when expressed in
      epithelial cells by inducing transformation and migration and inhibiting
      differentiation. Grown in three dimensions (3D) on Matrigel, the nontumorigenic
      mammary epithelial cell line MCF10A forms hollow, spherical acinar structures
      that maintain normal glandular features. Expression of oncogenes in these cells
      allows for the study of multiple aspects of tumor development in a 3D culture
      system. This study sought to examine the effects of LMP2 on the generation of
      MCF10A acini. LMP2 expression induced abnormal acini that were large, misshapen,
      and filled, indicating that LMP2 induced proliferation, impaired cellular
      polarization, and induced resistance to cell death, leading to luminal filling.
      Induction of cell death resistance required the PY, immunoreceptor tyrosine
      activation motif (ITAM), and YEEA signaling domains of LMP2 and activation of the
      Src and Akt signaling pathways. The PY domain was required for the inhibition of
      anoikis and also the delayed proliferative arrest of the LMP2-expressing cells.
      In addition to directly altering acinus formation, expression of LMP2 also
      induced morphological and protein expression changes consistent with epithelial
      mesenchymal transition (EMT) in a manner that required only the YEEA signaling
      motif of LMP2. These findings indicate that LMP2 has considerable transforming
      properties that are not evident in standard tissue culture and requires the
      ability of LMP2A to bind ubiquitin ligases and Src family kinases. 

PMID- 24109233
TI  - Fatal measles virus infection prevented by brain-penetrant fusion inhibitors.
AB  - Measles virus (MV) infection causes an acute childhood disease that can include
      infection of the central nervous system and can rarely progress to severe
      neurological disease for which there is no specific treatment. We generated
      potent antiviral peptide inhibitors of MV entry and spreading and MV-induced cell
      fusion. Dimers of MV-specific peptides derived from the C-terminal heptad repeat
      region of the MV fusion protein, conjugated to cholesterol, efficiently protect
      SLAM transgenic mice from fatal MV infection. Fusion inhibitors hold promise for
      the prophylaxis of MV infection in unvaccinated and immunocompromised people, as
      well as potential for the treatment of grave neurological complications of
      measles. 

PMID- 24109234
TI  - Targeting cell division cycle 25 homolog B to regulate influenza virus
      replication.
AB  - Influenza virus is a worldwide global health concern causing seasonal morbidity
      mortality and economic burden. Chemotherapeutics is available; however, rapid
      emergence of drug-resistant influenza virus strains has reduced its efficacy.
      Thus, there is a need to discover novel antiviral agents. In this study, RNA
      interference (RNAi) was used to screen host genes required for influenza virus
      replication. One pro-influenza virus host gene identified was dual-specificity
      phosphatase cell division cycle 25 B (CDC25B). RNAi screening of CDC25B resulted
      in reduced influenza A virus replication, and a CDC25B small-molecule inhibitor
      (NSC95397) inhibited influenza A virus replication in a dose-dependent fashion.
      Viral RNA synthesis was reduced by NSC95397 in favor of increased beta interferon
      (IFN-beta) expression, and NSC95397 was found to interfere with nuclear
      localization and chromatin association of NS1, an influenza virus protein. As NS1
      has been shown to be chromatin associated and to suppress host transcription, it
      is likely that CDC25B supports NS1 nuclear function to hijack host transcription
      machinery in favor of viral RNA synthesis, a process that is blocked by NSC95397.
      Importantly, NSC95397 treatment protects mice against lethal influenza virus
      challenge. The findings establish CDC25B as a pro-influenza A virus host factor
      that may be targeted as a novel influenza A therapeutic strategy. 

PMID- 24109235
TI  - Comprehensive analysis of human endogenous retrovirus group HERV-W locus
      transcription in multiple sclerosis brain lesions by high-throughput amplicon
      sequencing.
AB  - Human endogenous retroviruses (HERVs) of the HERV-W group comprise hundreds of
      loci in the human genome. Deregulated HERV-W expression and HERV-W locus ERVWE1
      encoded Syncytin-1 protein have been implicated in the pathogenesis of multiple
      sclerosis (MS). However, the actual transcription of HERV-W loci in the MS
      context has not been comprehensively analyzed. We investigated transcription of
      HERV-W in MS brain lesions and white matter brain tissue from healthy controls by
      employing next-generation amplicon sequencing of HERV-W env-specific reverse
      transcriptase (RT) PCR products, thus revealing transcribed HERV-W loci and the
      relative transcript levels of those loci. We identified more than 100 HERV-W loci
      that were transcribed in the human brain, with a limited number of loci being
      predominantly transcribed. Importantly, relative transcript levels of HERV-W loci
      were very similar between MS and healthy brain tissue samples, refuting
      deregulated transcription of HERV-W env in MS brain lesions, including the high
      level-transcribed ERVWE1 locus encoding Syncytin-1. Quantitative RT-PCR likewise
      did not reveal differences in MS regarding HERV-W env general transcript or
      ERVWE1- and ERVWE2-specific transcript levels. However, we obtained evidence for
      interindividual differences in HERV-W transcript levels. Reporter gene assays
      indicated promoter activity of many HERV-W long terminal repeats (LTRs),
      including structurally incomplete LTRs. Our comprehensive analysis of HERV-W
      transcription in the human brain thus provides important information on the
      biology of HERV-W in MS lesions and normal human brain, implications for study
      design, and mechanisms by which HERV-W may (or may not) be involved in MS. 

PMID- 24109236
TI  - NFX1-123 and human papillomavirus 16E6 increase Notch expression in
      keratinocytes.
AB  - The high-risk human papillomavirus (HR HPV) E6 oncoprotein binds host cell
      proteins to dysregulate multiple regulatory pathways, including apoptosis and
      senescence. HR HPV16 E6 (16E6) interacts with the cellular protein NFX1-123, and
      together they posttranscriptionally increase hTERT expression, the catalytic
      subunit of telomerase. NFX1-123 interacts with hTERT mRNA and stabilizes it,
      leading to greater telomerase activity and the avoidance of cellular senescence.
      Little is known regarding what other transcripts are dependent on or augmented by
      the association of NFX1-123 with 16E6. Microarray analysis revealed enhanced
      expression of Notch1 mRNA in 16E6-expressing keratinocytes when NFX1-123 was
      overexpressed. A moderate increase in Notch1 mRNA was seen with overexpression of
      NFX1-123 alone, but with 16E6 coexpression the increase in Notch1 was enhanced.
      The PAM2 motif and R3H protein domains in NFX1-123, which were important for
      increased hTERT expression, were also important in the augmentation of Notch1
      expression by 16E6. These findings identify a second gene coregulated by 16E6 and
      NFX1-123 and the protein motifs in NFX1-123 that are important for this effect. 

PMID- 24109237
TI  - The cytoprotective enzyme heme oxygenase-1 suppresses Ebola virus replication.
AB  - Ebola virus (EBOV) is the causative agent of a severe hemorrhagic fever in humans
      with reported case fatality rates as high as 90%. There are currently no licensed
      vaccines or antiviral therapeutics to combat EBOV infections. Heme oxygenase-1
      (HO-1), an enzyme that catalyzes the rate-limiting step in heme degradation, has
      antioxidative properties and protects cells from various stresses. Activated HO-1
      was recently shown to have antiviral activity, potently inhibiting the
      replication of viruses such as hepatitis C virus and human immunodeficiency
      virus. However, the effect of HO-1 activation on EBOV replication remains
      unknown. To determine whether the upregulation of HO-1 attenuates EBOV
      replication, we treated cells with cobalt protoporphyrin (CoPP), a selective HO-1
      inducer, and assessed its effects on EBOV replication. We found that CoPP
      treatment, pre- and postinfection, significantly suppressed EBOV replication in a
      manner dependent upon HO-1 upregulation and activity. In addition, stable
      overexpression of HO-1 significantly attenuated EBOV growth. Although the exact
      mechanism behind the antiviral properties of HO-1 remains to be elucidated, our
      data show that HO-1 upregulation does not attenuate EBOV entry or budding but
      specifically targets EBOV transcription/replication. Therefore, modulation of the
      cellular enzyme HO-1 may represent a novel therapeutic strategy against EBOV
      infection. 

PMID- 24109238
TI  - Functional antagonism of rhesus macaque and chimpanzee BST-2 by HIV-1 Vpu is
      mediated by cytoplasmic domain interactions.
AB  - Human immunodeficiency virus type 1 (HIV-1) Vpu enhances the release of viral
      particles from infected cells by interfering with the function of BST-2/tetherin,
      a cellular protein inhibiting virus release. The Vpu protein encoded by NL4-3, a
      widely used HIV-1 laboratory strain, antagonizes human BST-2 but not monkey or
      murine BST-2, leading to the conclusion that BST-2 antagonism by Vpu is species
      specific. In contrast, we recently identified several primary Vpu isolates, such
      as Vpu of HIV-1DH12, capable of antagonizing both human and rhesus BST-2. Here we
      report that while Vpu interacts with human BST-2 primarily through their
      respective transmembrane domains, antagonism of rhesus BST-2 by Vpu involved an
      interaction of their cytoplasmic domains. Importantly, a Vpu mutant carrying two
      mutations in its transmembrane domain (A14L and W22A), rendering it incompetent
      for interaction with human BST-2, was able to interact with human BST-2 carrying
      the rhesus BST-2 cytoplasmic domain and partially neutralized the ability of this
      BST-2 variant to inhibit viral release. Bimolecular fluorescence complementation
      analysis to detect Vpu-BST-2 interactions suggested that the physical interaction
      of Vpu with rhesus or chimpanzee BST-2 involves a 5-residue motif in the
      cytoplasmic domain of BST-2 previously identified as important for the antagonism
      of monkey and great ape BST-2 by simian immunodeficiency virus (SIV) Nef. Thus,
      our study identifies a novel mechanism of antagonism of monkey and great ape BST
      2 by Vpu that targets the same motif in BST-2 used by SIV Nef and might explain
      the expanded host range observed for Vpu isolates in our previous study. 

PMID- 24109239
TI  - Merkel cell polyomavirus small T antigen targets the NEMO adaptor protein to
      disrupt inflammatory signaling.
AB  - Merkel cell carcinoma (MCC) is a highly aggressive nonmelanoma skin cancer
      arising from epidermal mechanoreceptor Merkel cells. In 2008, a novel human
      polyomavirus, Merkel cell polyomavirus (MCPyV), was identified and is strongly
      implicated in MCC pathogenesis. Currently, little is known regarding the virus
      host cell interactions which support virus replication and virus-induced
      mechanisms in cellular transformation and metastasis. Here we identify a new
      function of MCPyV small T antigen (ST) as an inhibitor of NF-kappaB-mediated
      transcription. This effect is due to an interaction between MCPyV ST and the NF
      kappaB essential modulator (NEMO) adaptor protein. MCPyV ST expression inhibits
      IkappaB kinase alpha (IKKalpha)/IKKbeta-mediated IkappaB phosphorylation, which
      limits translocation of the NF-kappaB heterodimer to the nucleus. Regulation of
      this process involves a previously undescribed interaction between MCPyV ST and
      the cellular phosphatase subunits, protein phosphatase 4C (PP4C) and/or protein
      phosphatase 2A (PP2A) Abeta, but not PP2A Aalpha. Together, these results
      highlight a novel function of MCPyV ST to subvert the innate immune response,
      allowing establishment of early or persistent infection within the host cell. 

PMID- 24109240
TI  - Differential requirements of cellular and humoral immune responses for Fv2
      associated resistance to erythroleukemia and for regulation of retrovirus-induced
      myeloid leukemia development.
AB  - To assess the possible contribution of host immune responses to the exertion of
      Fv2-associated resistance to Friend virus (FV)-induced disease development, we
      inoculated C57BL/6 (B6) mice that lacked various subsets of lymphocytes with FV
      containing no lactate dehydrogenase-elevating virus. Fv2(r) B6 mice lacking
      CD4(+) T cells developed early polycythemia and fatal erythroleukemia, while B6
      mice lacking CD8(+) T cells remained resistant. Erythroid progenitor cells
      infected with spleen focus-forming virus (SFFV) were eliminated, and no
      polycythemia was observed in B cell-deficient B6 mice, but they later developed
      myeloid leukemia associated with oligoclonal integration of ecotropic Friend
      murine leukemia virus. Additional depletion of natural killer and/or CD8(+) T
      cells from B cell-deficient B6 mice resulted in the expansion of SFFV proviruses
      and the development of polycythemia, indicating that SFFV-infected erythroid
      cells are not only restricted in their growth but are actively eliminated in
      Fv2(r) mice through cellular immune responses. 

PMID- 24109241
TI  - Type I interferon and NF-kappaB activation elicited by herpes simplex virus gH/gL
      via alphavbeta3 integrin in epithelial and neuronal cell lines.
AB  - alphavbeta3 integrin represents a novel sensing system which detects herpes
      simplex virus (HSV) and bacterial constituents. In cooperation with Toll-like
      receptor 2 (TLR2), it elicits an innate response that leads to activation of type
      I interferon (IFN), NF-kappaB, and a specific set of cytokines. We report that
      this defensive branch is functional in cells which represent experimental models
      of epithelial, including keratinocytic, and neuronal cells. These are the major
      targets of HSV in vivo. HSV entered the three cell lines via distinct routes.
      Hence, the defensive response was independent of the route of virus entry.
      Soluble gH/gL sufficed to elicit type I IFN and NF-kappaB activation and
      represents the viral pathogen-associated molecular pattern (PAMP) of this defense
      system. 

PMID- 24109242
TI  - Evolution of the hemagglutinin protein of the new pandemic H1N1 influenza virus:
      maintaining optimal receptor binding by compensatory substitutions.
AB  - Pandemic influenza A H1N1 (pH1N1) virus emerged in 2009. In the subsequent 4
      years, it acquired several genetic changes in its hemagglutinin (HA). Mutations
      may be expected while virus is adapting to the human host or upon evasion from
      adaptive immune responses. However, pH1N1 has not displayed any major antigenic
      changes so far. We examined the effect of the amino acid substitutions found to
      be most frequently occurring in the pH1N1 HA protein before 1 April 2012 on the
      receptor-binding properties of the virus by using recombinant soluble HA trimers.
      Two changes (S186P and S188T) were shown to increase the receptor-binding avidity
      of HA, whereas two others (A137T and A200T) decreased binding avidity.
      Construction of an HA protein tree revealed the worldwide emergence of several HA
      variants during the past few influenza seasons. Strikingly, two major variants
      harbor combinations of substitutions (S186P/A137T and S188T/A200T, respectively)
      with opposite individual effects on binding. Stepwise reconstruction of the HA
      proteins of these variants demonstrated that the mutations that increase receptor
      binding avidity are compensated for by the acquisition of subsequent mutations.
      The combination of these substitutions restored the receptor-binding properties
      (avidity and specificity) of these HA variants to those of the parental virus.
      The results strongly suggest that the HA of pH1N1 was already optimally adapted
      to the human host upon its emergence in April 2009. Moreover, these results are
      in agreement with a recent model for antigenic drift, in which influenza A virus
      mutants with high and low receptor-binding avidity alternate. 

PMID- 24109244
TI  - Physical model for absorption of intraocular gas.
AB  - PURPOSE: To present a physical model for intraocular absorption of an inert gas
      used as a tamponade. METHODS: The absorption kinetics of gas in contact with the
      retinal surface is examined, including the changing geometry of the shrinking gas
      bubble inside the eye. RESULTS: An analytic solution is derived that predicts how
      the bubble dimensions change with time, yielding a formula for the lifetime of
      the gas bubble. Comparison to an experimental measurement shows that the analytic
      solution accurately replicates the time evolution of the bubble geometry. The
      result is also compared to an alternative exponential model, which does not
      predict a finite bubble lifetime. CONCLUSIONS: Further experiments are needed to
      discriminate between the surface absorption and exponential models.

PMID- 24109243
TI  - Human coronavirus OC43 nucleocapsid protein binds microRNA 9 and potentiates NF
      kappaB activation.
AB  - The human coronavirus OC43 is a major contributor to the common cold worldwide,
      though due to its low mortality rate, little research has focused on this human
      pathogen. The nucleocapsid is an essential structural protein with conserved
      functions across the coronavirus family. While a multitude of studies have
      examined nucleocapsid function, none have described the effects of OC43
      nucleocapsid on the transcription factor NF-kappaB. We report that the
      nucleocapsid protein of OC43 causes potentiation of NF-kappaB activation. This
      prolonged activation is the direct result of the ability of the nucleocapsid to
      bind RNA, specifically microRNA 9 (miR-9), which is a negative regulator of NF
      kappaB. This previously undescribed interaction between virus and host is a
      potential mechanism of immune evasion in RNA viruses. 

PMID- 24109245
TI  - Intracameral injection of tissue plasminogen activator to treat severe
      postoperative fibrinous reaction in iridocorneal endothelial syndrome.
AB  - Iridocorneal endothelial (ICE) syndrome is a primary endothelial abnormality that
      can cause a spectrum of iris changes, corneal edema, and glaucoma. Glaucoma
      secondary to ICE is difficult to manage because of the inflammatory reaction and
      fibrosis it can cause. We present a case of postoperative fibrinous reaction
      following endoscopic cyclophotocoagulation in ICE that caused aqueous tube shunt
      occlusion and high intraocular pressure. The condition was successfully managed
      with tissue plasminogen activator. 

PMID- 24109246
TI  - Congenital hypertrophy of the retinal pigment epithelium complicated by a
      choroidal neovascular membrane.
AB  - A 66-year-old woman presenting with a history of visual loss in her left eye was
      diagnosed with congenital hypertrophy of the retinal pigment epithelium
      accompanied by a choroidal neovascular membrane (CNVM) affecting the macula.
      Visual acuity improved after 2 treatments of verteporfin photodynamic therapy.
      Recurrent CNVM in the same eye 3 years later was stabilized and vision slowly
      improved with a series of intravitreal bevacizumab injections. 

PMID- 24109247
TI  - Acute retinal necrosis (ARN) in the context of neonatal HSV-2 exposure and
      subconjunctival dexamethasone: case report and literature review.
AB  - HSV-2 is an important cause of the acute retinal necrosis (ARN) syndrome in
      younger patients. We describe an atypical case of HSV-2 ARN in the context of
      neonatal exposure and subconjunctival steroid injection. Clinicians should be
      aware of the association of neonatal or congenital exposure to HSV-2 as a risk
      factor for this disease because early treatment may improve outcome and/or avoid
      involvement of both eyes. 

PMID- 24109248
TI  - Spontaneous resolution of ophthalmologic symptoms following bilateral traumatic
      carotid cavernous fistulae.
AB  - A 38-year-old woman developed bilateral carotid cavernous fistulae (CCF)
      following a motor vehicle collision. Her initial ophthalmologic findings included
      periorbital edema, palsies of the left oculomotor and abducens nerves, and
      residual dilated pupils. She subsequently developed significant optic disc edema
      and retinal vascular dilation bilaterally. Patients with similar injuries
      typically require neurosurgical or vascular intervention. In this case, the
      patient's signs resolved spontaneously by 21 months after onset, leaving no
      residual ocular deficits. 

PMID- 24109249
TI  - Artisan iris-fixated toric phakic intraocular lens for the correction of high
      astigmatism after deep anterior lamellar keratoplasty.
AB  - We report the refractive correction of high astigmatism in one eye of a 23-year
      old woman following deep anterior lamellar keratoplasty (DALK) using an Artisan
      iris-fixated, toric, phakic intraocular lens (IOL). One year after implantation,
      uncorrected and corrected distance visual acuities were both 20/25, refraction
      was -1.00 D cylinder, and the endothelial cell count was 1827 cells/mm(2). Iris
      fixated phakic IOLs are not recommended for every postkeratoplasty patient with
      high refractive error; however, this procedure can offer good outcomes in
      carefully selected cases of previous DALK. 

PMID- 24109250
TI  - A 48-year-old woman with redness, photophobia, and eye discomfort.

PMID- 24109251
TI  - Calcium hexa-kis(dihydrogen-phosphito)-stannate(IV), Ca[Sn(H2PO2)6], with some
      remarks on the so-called Ge2(H2PO2)6 structure type.
AB  - The title compound, Ca[Sn(H2PO2)6], was formed after a few days when tin(II)
      fluoride was allowed to react with phosphinic acid at ambient conditions. The
      structure consists of chains of Ca(2+) and Sn(4+) cations in octa-hedral sites
      with -3 symmetry bridged by bidentate hypophosphite anions. The chains are hexa
      gonally close packed along [001]. The discovery of the compound and the
      successful structure refinement provides strong evidence that an isostructural
      compound, originally described as the mixed-valence compound, Ge2[H2PO2]6
      [Weakley (1983 ?). J. Chem. Soc. Pak. 5, 279-281], must be reformulated as
      Ca[Ge(H2PO2)6]. 

PMID- 24109252
TI  - Tetraammine(carbonato-kappa(2) O,O')cobalt(III) perchlorate.
AB  - In the title complex, [Co(CO3)(NH3)4]ClO4, both the cation and anion lie on a
      mirror plane. The Co(III) ion is coordinated by two NH3 ligands and a chelating
      carbonato ligand in the equatorial sites and by two NH3 groups in the axial
      sites, forming a distorted octa-hedral geometry. In the crystal, N-H?O hydrogen
      bonds connect the anions and cations, forming a three-dimensional network. 

PMID- 24109253
TI  - K0.78Na0.22MoO2AsO4.
AB  - The title compound, potassium sodium dioxidomolybden-um(VI) arsenate,
      K0.78Na0.22MoO2AsO4, was synthesized by a solid-state reaction route. The
      structure is built up from corner-sharing MoO6 octa-hedra and AsO4 tetra-hedra,
      creating infinite [MoAsO8]infinity chains running along the b-axis direction. As,
      Mo and all but one O atom are on special positions (4c) with m symmetry and K
      (occupancy 0.78) is on a position (4a) of -1 in the tunnels. The possible motion
      of the alkali cations has been investigated by means of the bond-valance sum
      (BVS) model. The simulation shows that the Na(+) motion appears to be easier
      mainly along the b-axis direction. Structural relationships between the different
      compounds of the AMoO2AsO4 (A = Ag, Li, Na, K, Rb) series and MXO8 (M = V; X = P,
      As) chains are discussed. 

PMID- 24109254
TI  - Redetermination of MgCrO4.5H2O.
AB  - The CCD-data based redetermination of the crystal structure of the title
      compound, magnesium chromate(VI) penta-hydrate, confirms in principle the
      previous study based on precession film data [Bertrand et al. (1971 ?). C. R.
      Hebd. Seances Acad. Sci. Serie C, 272, 530-533.], but with all atoms refined with
      anisotropic displacement parameters and with all H atoms localized. This allowed
      an unambiguous assignment of the hydrogen-bonding pattern. MgCrO4.5H2O adopts the
      MgSO4.5H2O structure type. It contains two Mg(2+) sites on special positions with
      site symmetry -1, one tetra-hedral CrO4 group and five water mol-ecules. Four of
      them coordinate to the Mg(2+) cation, and one is an uncoordinating lattice water
      mol-ecule. The octa-hedral environment of the Mg(2+) cation is completed by two
      axial O atoms of CrO4 tetra-hedra. This arrangement leads to the formation of
      chains parallel to [011]. Adjacent chains are linked through O-H?O hydrogen bonds
      (one of them bifurcated), involving both the coordi-nating and lattice water mol
      ecules, into a three-dimensional network. 

PMID- 24109255
TI  - Distrontium trimanganese(II) bis-(hydro-gen-phosphate) bis-(ortho-phosphate).
AB  - The title compound, Sr2Mn3(HPO4)2(PO4)2, was synthesized under hydro-thermal
      conditions. In the structure, one of two Mn atoms is located on an inversion
      centre, whereas all others atoms are located in general positions. The framework
      structure is built up from two types of MnO6 octa-hedra (one almost undistorted,
      one considerably distorted), one PO3OH and one PO4 tetra-hedron. The
      centrosymmetric MnO6 octa-hedron is linked to two other MnO6 octa-hedra by edge
      sharing, forming infinite zigzag chains parallel to [010]. The PO3OH and PO4
      tetra-hedra connect these chains through common vertices or edges, resulting in
      the formation of sheets parallel to (100). The Sr(2+) cation is located in the
      inter-layer space and is bonded to nine O atoms in form of a distorted polyhedron
      and enhances the cohesion of the layers. Additional stabilization is achieved by
      a strong inter-layer O-H?O hydrogen bond between the PO3OH and PO4 units. The
      structure of the title phosphate is isotypic to that of Pb2Mn3(HPO4)2(PO4)2. 

PMID- 24109256
TI  - Penta-zirconium copper tribismuth.
AB  - Penta-zirconium copper tribismuth, Zr5CuBi3, crystallizes in the hexa-gonal
      Hf5CuSn3 structure type. The asymmetric unit contains two Zr sites (site
      symmetries 3.2 and m2m), one Cu site (site symmetry 3.m) and one Bi site (site
      symmetry m2m). The environment of the Bi atoms is a tetra-gonal anti-prism with
      one added atom and a coordination number (CN) of 9. The polyhedron around the Zr1
      atom is a defective cubo-octa-hedron with CN = 11. The bicapped hexa-gonal anti
      prism (CN = 14) is typical for Zr2 atoms. The Cu atom is enclosed in a eight
      vertex polyhedron (octa-hedron with two centered faces). The metallic type of
      bonding was indicated by an analysis of the inter-atomic distances and electronic
      structure calculation data. 

PMID- 24109257
TI  - RbCuFe(PO4)2.
AB  - A new iron phosphate, rubidium copper(II) iron(III) bis-(phosphate),
      RbCuFe(PO4)2, has been synthesized as single crystals by the flux method. This
      compound is isostructural with KCuFe(PO4)2 [Badri et al. (2011 ?), J. Solid State
      Chem. 184, 937-944]. Its structure is built up from Cu2O8 units of edge-sharing
      CuO5 polyhedra, inter-connected by FeO6 octa-hedra through common corners to form
      undulating chains that extend infinitely along the [011] and [01-1] directions.
      The linkage of such chains is ensured by the PO4 tetra-edra and the resulting
      three-dimensional framework forms quasi-elliptic tunnels parallel to the [101]
      direction in which the Rb(+) cations are located. 

PMID- 24109258
TI  - Na7Al3(As2O7)4.
AB  - The title compound, hepta-sodium trialuminium tetrakis(diarsenate), has been
      isolated as single crystals from a solid-state reaction. Its structure, which is
      isotypic with that of the Na7Fe3(X 2O7)4 (X = As, P) family of compounds,
      consists of AlO6 octa-hedra sharing their vertices with As2O7 groups, forming a
      three-dimensional [Al3(As2O7)4]infinity framework incorporating channels occupied
      by the sodium ions. One of the aluminium ions lies on a crystallographic twofold
      axis. The sodium ions are situated over ten positions (one with site symmetry 2),
      all but one of which are partially occupied. 

PMID- 24109259
TI  - Poly[MU-aqua-MU-(N,4-di-chloro-2-methyl-benzene-sulfonamidato)-potassium].
AB  - In the title compound, [K(C7H6Cl2NO2S)(H2O)] n , the K(+) cation is hepta
      coordinated by two water O atoms, a sulfonyl O atom from each of four different
      N,4-dichloro-2-methyl-benzene-sulfonamidate anions and a Cl atom of one of the
      anions. Further, K-O-K bridges form extensive polymeric chains along the b axis.
      In the crystal structure, the anions are linked into layers parallel to (100) by
      O-H?Cl and O-H?N hydrogen bonds. 

PMID- 24109260
TI  - catena-Poly[[tri-phenyl-tin(IV)]-MU-N-(4-acetyl-phen-yl)maleamato].
AB  - The crystal structure of the polymeric title compound, [Sn(C6H5)3(C12H10NO4)] n ,
      comprises polymeric chains whereby adjacent Sn atoms are bridged by carboxyl-ate
      and amide carbonyl O atoms [Sn-O = 2.115 (15) and 2.653 (1) A, respectively]. The
      Sn(IV) atom is five-coordinated showing a distorted trigonal-bipyramid geometry,
      with the three phenyl ipso-C atoms defining the trigonal plane and the axial
      positions occupied by O atoms [O-Sn-O = 171.91 (5) degrees ]. Intra-molecular N
      H?O hydrogen bonding leads to a seven-membered loop. There is an intra-molecular
      C-H?O inter-action within the polymeric chain. An inter-molecular C-H?O inter
      action along c links the polymeric chains into sheets which are linked into a
      three-dimensional network via C-H?pi inter-actions. 

PMID- 24109261
TI  - Bis(1-ethyl-4,4'-bipyridin-1-ium) bis-(1,2-di-cyano-ethene-1,2-di-thiol-ato
      kappa(2) S,S')nickelate(II).
AB  - In the anion of the title compound, (C12H13N2)[Ni(C4N2S2)2], the Ni(II) atom is
      coordinated by four S atoms from two 1,2-di-cyano-ethene-1,2-di-thiol-ate (mnt)
      ligands in a suqare-planar geometry. Weak C-H?N and C-H?S hydrogen bonds between
      the 1-ethyl-4,4'-bipyridin-1-ium cations and mnt anions and weak pi-pi inter
      actions between the pyridine rings of the cations [centroid-centroid distances =
      3.808 (3) and 3.972 (3) A] lead to a two-dimensional network parallel to (010). 

PMID- 24109262
TI  - (2,2'-Bipyrid-yl-kappa(2) N,N')bis-(eta(5)-penta-methyl-cyclo-penta-dien
      yl)barium.
AB  - In the title compound, [Ba(C10H15)2(C10H8N2)], the Ba-N distances are 2.798 (3)
      and 2.886 (3) A, and the Cp ring centroid distances to Ba(2+) are 2.7291 (7) and
      2.7192 (9) A. The angle between the N atoms in the bypyridine ligand and the
      metal ion is 56.80 (8) degrees  and the N-C-C-N torsion angle in the bi-pyridine
      ligand is 1.7 (4) degrees . The bi-pyridine ligand is almost planar, the dihedral
      angle formed by the intersection of the planes defined by the pyridyl rings being
      3.04 (19) degrees , and the angle between the plane defined by the Ba(2+) ion and
      the two bipyridyl N atoms and the plane defined by the 12 atoms of the bi
      pyridine ligand is 10.2 (3) degrees . The average Ba-N and Ba-centroid distances
      are 0.16 and 0.14 A longer, respectively, than the equivalent distances in the
      isotypic strontium compound [Kazhdan et al. (2008 ?). Acta Cryst. E64, m1134].
      This difference is in accord with the difference between the ionic radii of 0.16
      A suggested by Shannon [Acta Cryst. (1976 ?), A32, 751-767]. 

PMID- 24109263
TI  - Tris(2-formyl-phenolato-kappa(2) O,O')(1,10-phenanthroline-kappa(2)
      N,N')samarium(III).
AB  - In the title compound, [Sm(C7H5O2)3(C12H8N2)], the Sm(III) cation is coordinated
      by six O atoms from three bidentate 2-formyl-phenolate ligands and by two N atoms
      from 1,10-phenanthroline ligand. The resulting SmN2O6 coordination polyhedron is
      a distorted square anti-prism. In the crystal, C-H?O inter-actions connect mol
      ecules into chains along the b-axis direction. In addition, pi-pi stacking inter
      actions are observed with centroid-centroid distances in the range 3.6422 (13)
      3.7329 (13) A. 

PMID- 24109264
TI  - Tetra-kis(MU-3-chloro-benzoato-kappa(2) O:O')bis-[(N,N-di-ethyl-nicotinamide
      kappaN (1))copper(II)].
AB  - In the title centrosymmetric binuclear Cu(II) complex,
      [Cu2(C7H4ClO2)4(C10H14N2O)2], the two Cu(II) cations [Cu?Cu = 2.6314 (4) A] are
      bridged by four 3-chloro-benzoate (CB) anions. The four carboxyl-ate O atoms
      around each Cu(II) cation form a distorted square-planar arrangement, the
      distorted square-pyramidal coordination geometry being completed by the pyridine
      N atom of the N,N-di-ethyl-nicotinamide (DENA) mol-ecule. The dihedral angle
      between the benzene ring and the carboxyl-ate group is 4.49 (11) degrees  in one
      of the independent CB ligands and 12.00 (10) degrees  in the other. The benzene
      rings of the independent CB ligands are oriented at a dihedral angle of 84.13 (6)
      degrees . In the crystal, weak C-H?O hydrogen bonds link the binuclear complex
      mol-ecules into supra-molecular chains running along [101]. 

PMID- 24109265
TI  - {2-[2,2-Bis(4,4-dimethyl-4,5-di-hydro-1,3-oxazol-2-yl-kappaN)prop-yl]pyridine}
      dichlorido-iron(II).
AB  - The title compound,[FeCl2(C18H25N3O2)], has a distorted tetra-hedral Cl2N2
      coordination of the Fe(II) atom as a result of the constraints imposed by the 2
      [2,2-bis-(4,4-dimethyl-4,5-di-hydro-1,3-oxazol-2-yl)prop-yl]pyridine ligand. The
      pyridine ring is almost perpendicular to the six-membered chelated ring
      containing the metal atom [dihedral angle between their mean planes = 88.5 (1)
      degrees ]. 

PMID- 24109266
TI  - Dichloridobis[3-(4-meth-oxy-phen-yl)-2-methyl-5-(piperidin-1-yl)-2,3-di-hydro
      1,2,4-oxa-diazole-kappaN (4)]platinum(II).
AB  - In title compound, [PtCl2(C15H21N3O2)2], the Pt(II) cation, located on an
      inversion center, is coordinated by two Cl(-) anions and two 3-(4-meth-oxy-phen
      yl)-2-methyl-5-(piperidin-1-yl)-2,3-di-hydro-1,2,4-oxa-diazole ligands in a
      distorted Cl2N2 square-planar geometry. The di-hydro-oxa-diazole and piperidine
      rings display envelope (with the non-coordinating N atom as the flap atom) and
      chair conformations, respectively. In the crystal, weak C-H?Cl hydrogen bonds
      link the mol-ecules into supra-molecular chains running along the b axis. The
      piperidine ring is disordered over two positions with the occupancy ratio of
      0.528 (4):0.472 (4). 

PMID- 24109267
TI  - catena-Poly[heptyl-enedi-ammonium [[tetra-chloridobismuthate(III)]-MU-chlorido]].
AB  - The title organic-inorganic hybrid compound, {(C7H20N2)[BiCl5]} n , consists of
      distorted corner-joined [BiCl6] octa-hedra forming zigzag polymeric anionic
      chains parallel to [001], separated by columns of heptyl-enedi-ammonium cations.
      The asymmetric unit contains two crystallographically independent bis-muth metal
      atoms, one of which lies on an inversion centre and the other on a twofold axis.
      In the crystal, the polymeric chains and cations are linked by N-H?Cl hydrogen
      bonds, forming undulating layers parallel to (110). 

PMID- 24109268
TI  - Tri-aqua-(pyrazole-4-carboxyl-ato-kappaN (1))lithium.
AB  - In the monomeric title complex, [Li(C4H3N2O2)(H2O)3], the Li(+) cation is
      coordinated by a pyrazole N atom and three water mol-ecules in a distorted tetra
      hedral geometry. The carboxyl-ate group is deprotonated. The complex mol-ecules
      are involved in O-H?O and N-H?O hydrogen bonding, forming layers stacked along
      the b axis. 

PMID- 24109269
TI  - Di-aqua-bis-[2-(2-hy-droxy-eth-yl)pyridine-kappa(2) N,O]cobalt(II) dichloride.
AB  - In the title salt, [Co(C7H9NO)2(H2O)2]Cl2, the Co(II) cation, located on an
      inversion center, is N,O-chelated by two hy-droxy-ethyl-pyridine ligands and
      coordinated by two water mol-ecules in a distorted O4N2 octa-hedral geometry. In
      the crystal, the Cl(-) anions link with the complex cations via O-H?Cl hydrogen
      bonds, forming a three-dimensional supra-molecular architecture. pi-pi stacking
      is observed between the pyridine rings of adjacent mol-ecules [centroid-centroid
      distance = 3.5810 (11) A]. 

PMID- 24109270
TI  - Trichlorido(1,3-dimethyl-2,3-di-hydro-1H-imidazol-2-yl-idene-kappaC
      (2))aluminium(III).
AB  - The title compound, [Al(C5H8N2)Cl3], was prepared by a thermolytic decomposition
      under high-vacuum conditions and presents a formal adduct of an Arduengo carbene,
      1,3-dimethyl-1H-imidazol-2-yl-idene, and aluminium trichloride. The Al atom
      adopts a pseudo-tetra-hedral CCl3 coordination environment. All N and C atoms,
      the Al atom, one of the Cl atoms, and all aromatic H atoms of the mol-ecule lie
      on a mirror plane. As a result of the mirror symmetry of the mol-ecule, the H
      atoms of all methyl groups are disordered between symmetry-equivalent positions. 

PMID- 24109271
TI  - Bis[2-(1,3-benzo-thia-zol-2-yl)phenyl-kappa(2) C (1),N][1,3-bis-(4-bromo-phen
      yl)propane-1,3-dionato-kappa(2) O,O']iridium(III).
AB  - The title complex, [Ir(C15H9Br2O2)(C13H8NS)2], lies about a crystallographic
      twofold rotation axis passing through the Ir(III) atom and the central C atom of
      the bis-(bromo-phen-yl)propane-1,3-dionate ligand. The Ir(III) atom adopts a
      distorted octa-hedral geometry coordinated by two N atoms in the axial positions,
      and two C and two O atoms in the equatorial plane. The dihedral angle between the
      two thia-zole ring systems in the complex is 77.45 (10) degrees . 

PMID- 24109272
TI  - (5,10,15,20-Tetra-phenyl-porphyrinato-kappa(4) N)zinc-18-crown-6 (1/1).
AB  - In the title compound, [Zn(C44H28N4)].C12H24O6, the Zn(II) ion lies on an
      inversion center and the asymmetric unit contains one half of a Zn(TPP) complex
      (TPP = 5,10,15,20-tetra-phenyl-porphyrin dianion) and one half of a
      centrosymmetric 18-crown-6 mol-ecule. The Zn(TPP) complex exhibits a nearly
      planar conformation of the porphyrin core [maximum deviation = 0.106 (2) A] with
      an average Zn-N distance of 2.047 (2) A. The title compound is considered as a
      one-dimensional polymer along [010], in which the Zn(TPP) moiety is linked to the
      closest O atoms of two symmetry-related 18-crown-6 mol-ecules with a Zn-O
      distance of 2.582 (1) A, completing a distorted octahedral coordination
      environment of the metal ion. The chains are mainly sustained by weak C-H?pi
      inter-actions. An ethyl-ene group of the 18-crown-6 mol-ecule is disordered over
      three sites with occupancies of 0.50, 0.25 and 0.25. 

PMID- 24109273
TI  - Dichloridobis[3-(4-chloro-phen-yl)-2,N,N-trimethyl-2,3-di-hydro-1,2,4-oxa-diazole
      5-amine-kappaN (4)]platinum(II)-4-chloro-benzaldehyde (1/1).
AB  - In the title 1:1 co-crystal, [PtCl2(C11H14ClN3O)2].C7H5ClO, the coordination
      polyhedron of the Pt(II) atom is slightly distorted square-planar with the
      chloride and 2,3-di-hydro-1,2,4-oxa-diazole ligands mutually trans, as the Pt
      atom lies on an inversion center. The 4-chloro-benzaldehyde mol-ecules are
      statistically disordered about an inversion centre with equal occupancies for the
      two positions. The Pt(II) complex forms a three-dimensional structure through C
      H?Cl and weaker C-H?O inter-actions with the 4-chloro-benzaldehyde mol-ecule. 

PMID- 24109274
TI  - (2,2'-Bi-pyridine-kappa(2) N,N')tetra-kis-(dimethyl sulfoxide-kappaO)copper(II)
      bis-(perchlorate).
AB  - The title compound, [Cu(C2H6OS)4(C10H8N2)](ClO4)2, contains a Cu(II) ion with a
      distorted octa-hedral coordination environment, bonded by four O atoms of the
      monodentate dimethyl sulfoxide ligands and two N atoms of the bidentate chelating
      2,2'-bi-pyridine ligand. The equatorial Cu-N and Cu-O bond lengths are in the
      range 1.979 (2)-1.998 (3) A. The axial Cu-O bond distances are 2.365 (2) and
      2.394 (2) A. In the crystal, the complex cations and perchlorate anions are
      connected by numerous C-H?O hydrogen bonds, which leads to additional
      stabilization of the structure. The perchlorate anion is disordered over two sets
      of sites with a 0.716 (3):0.284 (3) occupancy ratio. 

PMID- 24109275
TI  - Tetra-kis(pyridine-kappaN)bis-(tetrafluorido-borato-kappaF)copper(II).
AB  - In the title complex, [Cu(BF4)2(C5H5N)2], the Cu(II) ion is in an octa-hedral
      coordination environment and is surrounded by four pyridine and two tetra
      fluoridoborate mol-ecules. The four pyridine mol-ecules are coordinated to the
      copper ion through their N atoms in the equatorial plane and display a right
      handed screw arrangement around the Cu(II) ion. The remaining two trans positions
      in the octa-hedron are occupied by the BF4 (-) anions, each coordinating weakly
      through an F atom. The crystal packing shows a two-dimensional sheet structure
      parallel to the ab plane that is formed by C-H?F hydrogen-bonding inter-actions. 

PMID- 24109276
TI  - catena-Poly[[[tetra-aqua-magnesium]-trans-MU-[(piperazine-1,4-diium-1,4-di-yl)bis
      (methyl-ene)]di-phospho-nato] hemihydrate].
AB  - The structure of the title polymer, }[Mg(C6H14N2O6P2)(H2O)4].0.5H2O} n , is based
      on centrosymmetric MgO6 octahedra, which are linked by [(piperazine-1,4-diium-1,4
      di-yl)bis-(methyl-ene)]di-phospho-nate ligands, forming chains parallel to [1-1
      1]. These chains are connected via hydrogen bonds primarily formed between the
      phospho-nate groups and water mol-ecules. The latter constitute four of the
      corners of the MgO6 polyhedra and bind to the O atoms of the phospho-nate groups
      of neighbouring chains. The lattice water molecule is disordered around an
      inversion centre, exhibiting an occupancy of 0.25. 

PMID- 24109277
TI  - Di-aqua-bis-(pyridine-2-carboxyl-ato-kappa(2) N,O)zinc di-methyl-formamide
      hemisolvate.
AB  - In the title compound, [Zn(C6H4NO2)2(H2O)2].0.5C3H7NO, the Zn(II) ion is
      coordinated in a distorted octa-hedral N2O4 environment by two N,O-chelating
      pyridine-2-carboxyl-ate ligands and two cis water mol-ecules. The chelating
      pyridine-2-carboxyl-ate ligands create two five-membered Zn/N/C/C/O rings, which
      form a dihedral angle of 86.4 (2) degrees . In the crystal, O-H?O hydrogen bonds
      link the complex mol-ecules into a two-dimensional network parallel to (100). The
      di-methyl-formamide solvent mol-ecule is disordered about a twofold rotation
      axis. 

PMID- 24109278
TI  - Bis[MU-3,5-bis-(pyridin-2-yl)pyrazolato]bis-[(hexa-fluoro-phosphato)copper(II)].
AB  - The title dinuclear complex mol-ecule, [Cu2(C13H9N4)2(PF6)2], lies about an
      inversion center. The Cu(II) atom shows a square-pyramidal coordination geometry
      with the basal plane formed by four N atoms of the two bis-chelating 3,5-bis
      (pyridin-2-yl)pyrazolate ions and with one F atom of the hexa-fluoro-phosphate
      ion in the apical position. Mol-ecules are stacked in a column along the a axis
      through C-H?F hydrogen bonds. The columns are further linked by other C-H?F
      hydrogen bonds, forming a three-dimensional network. 

PMID- 24109279
TI  - Bis{N-benzyl-N-[2-(thio-phen-2-yl)eth-yl]di-thio-carbamato-kappa(2)
      S,S'}lead(II).
AB  - The mol-ecule of the title compound, [Pb(C14H14NS3)2], is located on a twofold
      rotation axis. The di-thio-carbamate anion S,S'-chelates to the Pb(II) atom,
      which shows a Psi-trigonal-bipyramidal coordination. The thio-phene ring is
      disordered over two positions, the major component having 71.3 (7)% occupancy.
      The mol-ecular conformation is stabilized by intra-molecular C-H?S inter-actions.

PMID- 24109280
TI  - Aqua-bis-(3-chloro-benzoato-kappaO)bis-(N,N-di-ethyl-nicotinamide
      kappaN)copper(II).
AB  - The title compound, [Cu(C7H4ClO2)2(C10H14N2O)2(H2O)], has twofold symmetry with
      the Cu(II) cation and the O atom of the coordinating water mol-ecule located on
      the axis. The Cu(II) cation is coordinated by two carboxyl-ate O atoms of chloro
      benzoate (CB) anions, two N atoms of N,N-di-ethyl-nicotinamide (DENA) ligands and
      one water mol-ecule in a distorted N2O3 square-pyramidal geometry. The benzene
      and pyridine rings are oriented at a dihedral angle of 82.51 (6) degrees . In the
      anionic ligand, the carboxyl-ate group is twisted away from the attached benzene
      ring by 12.85 (11) degrees . In the crystal, O-H?O hydrogen bonds between the
      coordinating water mol-ecule and the carboxyl group link the complex mol-ecules
      into supra-molecular chains running along the c-axis direction. 

PMID- 24109281
TI  - (Methanol-kappaO)-cis-dioxido{(4Z,N'E)-N'-[(Z)-4-oxido-4-phenyl-but-3-en-2-yl
      idene]iso-nicotino-hydrazidato}molybdenum(VI).
AB  - In the title complex, [Mo(C16H13N3O2)O2(CH3OH)], the deprotonated Schiff base (E)
      N'-[(Z)-4-oxido-4-phenyl-but-3-en-2-yl-idene]isonicotinohydrazide coordinates in
      a meridional fashion through the enolate O-, imine N- and amidate O-atom donors
      to the Mo atom of a cis-[MoO2](2+) core. The sixth coordination site of
      molybdenum is occupied by the O atom of a methanol mol-ecule. In this complex,
      the NO5 coordination sphere adopts a distorted octa-hedral coordination geometry.
      The metal atom is shifted by 0.335 (1) A from the square plane defined by the
      three donor atoms of the Schiff base ligand and one oxide group towards the
      second oxide group in the cis position. In the crystal, the complex forms
      inversion dimers through a pair of O-H?N hydrogen bonds involving the methanol 
      OH group and the pyridine N atom. Additional C-H?O contacts stack the mol-ecules
      along the b axis. 

PMID- 24109282
TI  - Tetra-ethyl-ammonium dicyanido(5,10,15,20-tetra-phenyl-porphyrinato)ferrate(III)
      di-chloro-methane monosolvate.
AB  - The title compound, (C8H20N)[Fe(C44H28N4)(CN)2].CH2Cl2 or (Et4N)[Fe(TPP)(CN)2],
      was recrystallized from di-chloro-methane-diethyl ether. The compound
      crystallizes with the two unique halves of the Fe(III) porphyrinato complex, one
      tetra-ethyl-ammonium cation and one inter-stitial di-chloro-methane mol-ecule
      within the asymmetric unit. Both anionic Fe(III) complexes exhibit inversion
      symmetry. Both the cation and the solvent mol-ecules show positional disorder.
      The cation is disordered over two sets of sites with an occupancy ratio of 0.710
      (3):0.290 (3); the solvent mol-ecule is disordered over three positions with a
      0.584 (6):0.208 (3):0.202 (5) ratio. The crystal packing features columns of
      [Fe(TPP)(CN)2](-) anions that propagate along [001]. The columns further pack
      into layers that are parallel to (011) and also include the Et4N(+) cations. The
      inter-stitial CH2Cl2 mol-ecules appear in the inter-layer space. This complex may
      serve as a useful precursor for the assembly of multinuclear and extended CN
      bridged complexes for the design of single-mol-ecule and single-chain magnets,
      respectively. 

PMID- 24109283
TI  - Poly[[MU-bis-(4-nitro-phen-yl) phosphato-kappa(2) O,O']sodium].
AB  - The title compound, [Na(C12H8N2O8P)], consists of one Na(+) cation and one bis-(p
      nitro-phen-yl)phosphate anion with a considerable distortion of the phosphate
      tetra-hedron due to the presence of two P-O ester bonds. The anion bridges five
      Na(+) cations whereby each cation is chelated by the nitro O atoms of one anion
      and bonded via a nitro O atom and phosphate O atoms to four other anions. This
      bridging arrangement leads to the formation of double layers parallel to (001).
      Adjacent layers are linked through weak C-H?O hydrogen bonds. 

PMID- 24109284
TI  - catena-Poly[[aqua-bis-(3-chloro-benzoato-kappa(2) O,O')cadmium]-MU-N,N-di-ethyl
      nico-tin-amide-kappa(2) N (1):O].
AB  - In the crystal of the title Cd(II) polymeric complex,
      [Cd(C7H4ClO2)2(C10H14N2O)(H2O)] n , the Cd(II) cation is chelated by two chloro
      benzoate anions and coordinated by two N,N-di--ethyl-nicotinamide (DENA) ligands
      and one water mol-ecule in a distorted NO6 penta-gonal-bipyramidal geometry. The
      Cd(II) cations are bridged by the pyridine N atom and carbonyl O atom of the DENA
      ligand to form a polymeric chain running along the b axis. Inter-molecular O-H?O
      hydrogen bonds between coordinating water mol-ecules and carboxyl-ate groups link
      adjacent chains into layers parallel to the bc plane. pi-pi contacts between
      benzene rings [shortest centroid-centroid distance = 3.912 (2) A] further
      stabilizes the crystal structure. In the mol-ecule, weak C-H?O hydrogen bonds
      occur between the pyridine ring and carboxyl-ate groups; the dihedral angles
      between the carboxyl-ate groups and adjacent benzene rings are 4.6 (3) and 12.8
      (3) degrees , while the benzene rings are oriented at a dihedral angle of 1.89
      (13) degrees . 

PMID- 24109285
TI  - (Azido-kappaN){(E)-2-[1-(pyridin-2-yl)ethyl-idene-amino]-phenolato-kappa(3)
      N,N',O}copper(II).
AB  - In the title complex, [Cu(C13H11N2O)(N3)], the Cu(II) cation is four-coordinated
      by an N2O donor set of the tridentate Schiff base ligand and by the terminal N
      atom of the azide anion, forming a slightly distorted square-planar
      configuration. 

PMID- 24109286
TI  - Diammonium tetra-kis-(iso-thio-cyanato)-zincate-1,4,10,13,16-hexa-oxa-cyclo-octa
      deca-ne-water (1/2/1).
AB  - The title compound, (NH4)2[Zn(NCS)4].2C12H24O6.H2O, the result of the reaction of
      ammonium thio-cyanate, 18-crown-6 and zinc(II) chloride in aqueous solution,
      exhibits an unusual supra-molecular structure. The Zn atom, two of the thio
      cyanate chains and a water mol-ecule, disordered over two positions, lie on a
      mirror plane. The macrocycle adopts a conformation with approximate D 3d
      symmetry. The ammonium mol-ecules are contained within the bowl of the macrocycle
      via extensive N-H?O hydrogen bonds and the complex mol-ecules are linked via N
      H?S hydrogen bonds, forming chains along the c-axis direction. The macrocycle is
      disordered over two positions [refined occupancy ratio = 0.666 (8):0.334 (8)].
      The S atoms of two iso-thio-cyanate ligands are disordered within and about the
      mirror plane. 

PMID- 24109287
TI  - [5,10,15,20-Tetra-kis(4-meth-oxy-phen-yl)porphyrinato]zinc di-chloro-methane
      disolvate.
AB  - In the title compound, [Zn(C48H36N4O4)].2CH2Cl2, the Zn(II) ion lies on an
      inversion center and is coordinated in an almost ideal square-planar geometry.
      The asymmetric unit also contains one di-chloro-methane solvent mol-ecule. The
      unique meth-oxy-substituted benzene rings form dihedral angles of 59.38 (6) and
      66.77 (6) degrees  with the mean plane (r.m.s. deviation of fitted atoms = 0.0282
      A) of the atoms in the porphyrin core. The packing is characterized by close
      contacts between the Zn(II) ion and two symmetry-related mol-ecules through the O
      atoms of a meth-oxy-phenyl group [Zn?O = 2.694 (2) A], forming a two-dimensional
      network parallel to (100). 

PMID- 24109288
TI  - trans-Bis(MU-benzene-thiol-ato-kappa(2) S:S)bis[chlorido-(tri-phenyl-phosphane
      kappaP)palladium(II)] chloro-form disolvate.
AB  - The title compound, [Pd2Cl2(C6H5S)2(C18H15P)2].2CHCl3, contains a centrosymmetric
      dinuclear palladium complex with the Pd(II) cation in a slightly distorted square
      planar coordination environment. The Pd(II) cations are bridged by the S atoms of
      two benzene-thiol-ate ligands with different Pd-S distances [2.2970 (11) and
      2.3676 (11) A]. The coordination of the metal atom is completed by a chloride
      anion [2.3383 (11) A] and a tri-phenyl-phosphane ligand [2.2787 (11) A]. Weak C
      H?Cl inter-actions are present between complex mol-ecules and the CHCl3 solvent
      mol-ecule. The latter is disordered over two positions in a 0.792 (8):0.208 (8)
      ratio. The crystal under investigation was found to be twinned by nonmerohedry,
      with a fraction of 73.4 (1)% for the major twin component. 

PMID- 24109289
TI  - Bis(cyclo-hexyl-ammonium) tetra-chlorido-(oxalato)stannate(IV).
AB  - The title salt, (C6H14N)2[Sn(C2O4)Cl4], was obtained as a by-product from the
      reaction between 2C6H14N(+).C2O4 (2-).1.5H2O and SnCl2.2H2O. The cyclo-hexyl
      ammonium cation has a chair conformation. The complex anion consists of an
      oxalate anion chelating the SnCl4 moiety, resulting in a distorted octa-hedral
      coordination sphere of the Sn(IV) atom with the O atoms in equatorial cis
      positions. In the crystal, cations and anions are linked through N-H?O and N-H?Cl
      inter-actions into a layered arrangement parallel to (100). 

PMID- 24109290
TI  - trans-Acetyl-dicarbon-yl(eta(5)-cyclo-penta-dien-yl)[tris-(furan-2-yl)phosphane
      kappaP]molybdenum(II).
AB  - The title compound, [Mo(C5H5)(C2H3O)(C12H9O3P)(CO)2], was prepared by reaction of
      [Mo(C5H5)(CO)3(CH3)] with tris-(furan-2-yl)phosphane. The Mo(II) atom exhibits a
      four-legged piano-stool coordination geometry with the acetyl and phosphine
      ligands trans to each other. The O atom of the acetyl ligand points down, away
      from the Cp ring. In the crystal, mol-ecules form centrosymmetrical dimers via pi
      pi inter-actions between furyl rings [the centroid-centroid distance is 3.396 (4)
      A]. The dimers are linked by C-H?O hydrogen bonds into layers parallel to (100). 

PMID- 24109291
TI  - catena-Poly[ammonium [aqua-bis-(MU-2,3,5,6-tetra-oxo-4-nitro-pyridin-4
      ido)argentate(I)]].
AB  - In the title compound, {(NH4)[Ag(C5HN2O6)2(H2O)]} n , the Ag(I) cation is seven
      coordinated and is surrounded by four oxo O atoms of the 2,3,5,6-tetra-oxo-4
      nitro-pyridin-4-ide species [Ag-O = 2.3848 (19), 2.4931 (18), 2.5361 (18) and
      2.573 (2) A], two nitro O atoms [Ag-O = 2.644 (2) and 2.661 (2) A], and one water
      mol-ecule [Ag-O = 2.3133 (19) A]. The pyridin-4-ide mono-anions act as
      polydentate bridging ligands and form a three-dimensional network that is
      stabilized through O-H?O and N-H?O hydrogen bonds involving the coordinating
      water mol-ecule and the imide function as donator groups. The ammonium cations
      are located in the cavities of the framework and are also involved in hydrogen
      bonding to O atoms of the ligand. 

PMID- 24109292
TI  - 4-Chloro-butyl 7-chloro-1-cyclo-propyl-4-(1,3-diethyl-4,6-dioxo-2-sulfanyl-idene
      1,3-diazinan-5-yl-idene)-6-fluoro-1,4-di-hydro-quinoline-3-carboxyl-ate.
AB  - The title compound, C25H26Cl2FN3O4S, contains two bio-active moieties (thio
      barbituric acid and fluoro-quinolone). In the crystal, mol-ecules are linked via
      C-H?O and C-H?F hydrogen bonds, forming two-dimensional slab-like networks lying
      parallel to the bc plane. The benzene ring substituted by F and Cl atoms and the
      4-chloro-butyl group seem to be partly disordered, however attempts to model the
      disorder were unsuccessful. 

PMID- 24109293
TI  - 2-[1'-(Benz-yloxy)spiro-[indane-1,2'-pyrrolidine]-5'-yl]aceto-nitrile.
AB  - In the title compound, C21H22N2O, the planes of the two six-membered rings make a
      dihedral angle of 89.51 (7) degrees . The pyrrolidine ring has a puckering
      amplitude q 2 = 0.418 (3) and a pseudo-rotation phase angle phi2 = -166.8 (5),
      adopting a twist conformation (T). The other five-membered ring has a puckering
      amplitude q 2 = 0.247 (2) and a pseudo-rotation phase angle phi2 = -173.7 (5),
      adopting an envelope conformation with the CH2 atom adjacent to the C atom common
      with the pyrrolidine ring as the flap. In the crystal, mol-ecules are linked via
      C-H?N, enclosing R (2) 2(20) rings, forming chains propagating along [100]. The
      aceto-nitrile group is disordered over two positions and was refined with a fixed
      occupancy ratio of 0.56:0.44. 

PMID- 24109294
TI  - 1'-(1,3-Diphenyl-1H-pyrazol-4-yl)-1''-(prop-2-en-1-yl)-2',3',5',6',7',7a'-hexa
      hydro-1'H-di-spiro-[1-benzo-pyran-3,2'-pyrrolizine-3',3''-indoline]-2'',4-dione
      0.75-hydrate.
AB  - In the central aza-bi-cyclo-octane unit of the title compound,
      C40H34N4O3.0.75H2O, the peripheral pyrrolidine ring adopts an envelope
      conformation with the N atom deviating by 0.209 (2) A, whereas the other
      pyrrolidine ring adopts a twisted conformation with the bridging N and C atoms
      deviating by -0.218 (2) and 0.236 (3) A, respectively, from the rest of the ring.
      The pyrazole ring forms dihedral angles of 42.36 (7) and 24.07 (8) degrees  with
      its C- and N-attached phenyl groups, respectively. The solvent water mol-ecule
      has a partial occupancy of 0.75. In the crystal, the water mol-ecules link the
      fused-ring mol-ecules into chains along the b axis via O-H?N and O-H?O hydrogen
      bonds. The crystal packing is further stabilized by C-H?pi inter-actions
      involving a methyl-ene group of the pyran ring and the C-attached benzene ring on
      the pyrazole ring. 

PMID- 24109295
TI  - 3-{5-Bromo-2-[(tri-phenyl-phosphanyl-idene)amino]-phen-yl}-4,5-di-hydro-1,2,3-oxa
      diazol-3-ylium-5-olate.
AB  - In general, sydnone compounds are synthesized with an aromatic substituent at the
      N-3 position and this feature adds to the stability of the mesoionic five
      membered heterocyclic ring. In the title compound, C26H19BrN3O2P, the aromatic
      substitutent is tri-phenyl-phosphine 4-bromo-phenyl-imide. The dihedral angle
      between the planes of the sydnone and the attached phenyl ring is 45.98 (7)
      degrees . In the crystal, the mol-ecules packed as pairs in which the sydnone
      rings lie in parallel planes separated by 0.849 A and sandwiched between two
      parallel phenyl rings. The mol-ecules inter-act through cyclic C-H?O=C hydrogen
      bonds. 

PMID- 24109296
TI  - (2S,3R)-3-(2-Bromo-phen-yl)-2-nitro-2,3,6,7-tetra-hydro-1-benzo-furan-4(5H)-one.
AB  - The title compound, C14H12BrNO4, has two chiral C atoms. The C atom next to the O
      atom in the di-hydro-furan ring has an S configuration, while the adjacent chiral
      C atom has an R configuration. The cyclo-hex-2-enone and di-hydro-furan rings
      both adopt envelope conformations, with the flap atoms (middle CH2 in cyclo-hex-2
      enone and NO2-substituted C in di-hydro-furan) lying 0.612 (3) and 0.295 (2) A,
      respectively, from the mean plane of the remaining atoms. The dihedral angle
      between the mean planes of the furan and benzene rings is 80.0 (3) degrees . In
      the crystal, the mol-ecules are linked by C-H?O inter-actions, generating a three
      dimensional network. 

PMID- 24109297
TI  - 2,2'-[(4-Methyl-2-phenyl-imidazolidine-1,3-di-yl)bis-(methyl-ene)]diphenol.
AB  - The methyl-substituted imidazolidine ring of the title compound, C24H26N2O2,
      adopts an envelope conformation with the N atom adjacent to the methyl-ene group
      as the flap. The meth-yl-ethyl-ene fragment in this ring is disordered over two
      positions with an occupancy ratio of 0.899 (4):0.101 (4). The hy-droxy-benzyl
      groups are inclined at 71.57 (15) and 69.97 (19) degrees  to the mean plane of
      major disorder component of the heterocyclic ring with an inter-planar angle
      between the two hy-droxy-benzyl groups of 66.00 (5) degrees . The phenyl substit
      uent approaches a nearly perpendicular orientation relative to the mean plane of
      the imidazolidine ring, making a dihedral angle of 75.60 (12) degrees . This
      conformation is stabilized by two intra-molecular O-H?N bonds, which generate
      S(6) ring motifs. 

PMID- 24109298
TI  - 14-Meth-oxy-4,6-dimethyl-9-phenyl-8,12-dioxa-4,6-di-aza-tetra-cyclo
      [8.8.0.0(2,7).0(13,18)]octa-deca-2(7),13,15,17-tetra-ene-3,5,11-trione.
AB  - The title compound, C23H20N2O6, crystallizes with two mol-ecules in the
      asymmetric unit in which the dihedral angles between the mean planes of the pyran
      and phenyl rings are 66.6 (1) and 61.9 (1)  degrees . The fused pyrone and pyran
      rings each adopts a sofa conformation. In the crystal, C-H?O hydrogen bonds link
      the mol-ecules, forming a two-dimensional network parallel to [001]. 

PMID- 24109299
TI  - (Naphthalen-1-yl){2-[(5,6,7,8-tetrahydronaphthalen-2
      yl)carbonyl]phenyl}methanone.
AB  - The title compound C28H22O2, basically consists of three ring systems, viz. a
      central benzene ring, with a lateral napthalene group to which it subtends a
      dihedral angle of 66.56 (4) degrees  and a tetra-hydro-pyran ring exhibiting a
      half-chair conformation. The mol-ecular structure is stabilized by a weak intra
      molecular C-H?O inter-action, while the crystal packing features weak C-H?pi
      contacts. 

PMID- 24109300
TI  - 5-Fluoro-3-phenyl-N'-(4-propyl-cyclo-hexyl-idene)-1H-indole-2-carbohydrazide.
AB  - In the title compound, C24H26FN3O, the cyclo-hexane ring adopts a chair
      conformation; the propyl substituent is in an equatorial orientation and the bond
      angle sum at the C atom bonded to the carbohydrazide N atom is 360.0 degrees .
      The dihedral angle between the 1H-indole ring system and the phenyl ring is 82.77
      (13) degrees . A weak intra-molecular C-H?pi contact occurs. In the crystal,
      pairs of mol-ecules related by a crystallographic twofold axis are linked by
      bifurcated N-H?(O,N) hydrogen bonds; a C-H?O inter-action occurs between the same
      pair. The dimers are linked by C-H?F and C-H?pi inter-actions, generating a three
      dimensional network. 

PMID- 24109301
TI  - 1-(2,4-Di-nitro-phen-yl)-2-[(E)-2,4,5-tri-meth-oxy-benzyl-idene]hydrazine.
AB  - The title compound, C16H16N4O7, is close to being planar, with a dihedral angle
      of 3.15 (11) degrees  between the benzene rings. The meth-oxy groups at the ortho
      and para-positions of the 2,4,5-tri-meth-oxy-phenyl group are almost coplanar
      with the ring [deviations of the C atoms = 0.017 (2) and -0.025 (2) A,
      respectively], whereas the meta-meth-oxy group deviates slightly [C-atom
      displacement = 0.162 (2) A]. Both the ortho- and para-nitro groups are close to
      being coplanar with their attached ring [dihedral angles = 7.81 (12) and 8.56
      (11) degrees , respectively]. An intra-molecular N-H?O hydrogen bond generates an
      S(6) ring motif. In the crystal, inversion dimers linked by pairs of N-H?O
      hydrogen bonds involving the same H atom as the intra-molecular bond generate R 2
      (2)(12) loops. The dimers are linked by weak C-H?O inter-actions into sheets
      parallel to the (10-4) plane and the sheets are stacked by pi-pi inter-actions,
      with a centroid-centroid distance of 3.5974 (14) A. 

PMID- 24109302
TI  - 3-(4-Bromo-phenyl-sulfin-yl)-2,5,6-trimethyl-1-benzo-furan.
AB  - In the title compound, C17H15BrO2S, the dihedral angle between the mean plane
      [r.m.s. deviation = 0.003 (2) A] of the benzo-furan ring system and the mean
      plane [r.m.s. deviation = 0.006 (2) A] of the 4-bromo-phenyl ring is 83.09 (7)
      degrees . In the crystal, weak C-H?pi inter-actions are observed. 

PMID- 24109303
TI  - Bifenox: methyl 5-(2,4-di-chloro-phen-oxy)-2-nitro-benzoate.
AB  - In the title compound, the herbicide bifenox, C14H9Cl2NO5, the dihedral angle
      between the dichlorobenzene and nitro-benzene rings is 78.79 (14) degrees . In
      the crystal, C-H?O hydrogen bonds give rise to a three-dimensional network
      structure in which there are both a pi-pi inter-action [ring centroid separation
      = 3.6212 (16) A] and a C-Cl?pi inter-action [Cl?ring centroid = 3.4754 (8) A]. In
      addition, short Cl?Cl contacts [3.3767 (11) and 3.3946 (11) A] are present. 

PMID- 24109304
TI  - Napropamide.
AB  - THE TITLE COMPOUND [SYSTEMATIC NAME: N,N-diethyl-2-(naphthalen-1-yl
      oxy)propanamide], C17H21NO2, crystallizes with two independent mol-ecules in the
      asymmetric unit in which the dihedral angles between the naphthalene ring systems
      and the amide groups are 88.1 (9) and 88.7 (3) degrees . Four C-H?O hydrogen
      bonds stabilize the crystal structure. 

PMID- 24109305
TI  - 5''-(4-Nitro-benzyl-idene)-7'-(4-nitro-phen-yl)-1''-methyl-1',3',5',6',7',7a'
      hexa-hydro-dispiro-[ace-naphthyl-ene-1,5'-pyrrolo-[1,2-c][1,3]thia-zole-6',3''
      piperidine]-2,4''(1H)-dione including an unknown solvate.
AB  - The title compound, C35H28N4O6S, crystallizes with two mol-ecules in the
      asymmetric unit. In both mol-ecules, the piperidine ring adopts a shallow-chair
      conformation, the thia-zole ring adopts a twisted conformation about the Cm-N
      bond (m = methine) and the pyrrole ring adopts an envelope conformation with the
      C atom shared with the thia-zole ring as the flap. In the crystal, inversion
      dimers linked by pairs of C-H?O inter-actions generate R 2 (2)(34) loops for one
      of the asymmetric mol-ecules. Further C-H?O links also involving the other mol
      ecule lead to a three-dimesional network. The contribution of the highly
      disordered solvent to the scattering was removed with SQUEEZE option of PLATON
      [Spek (2009 ?). Acta Cryst. D65, 148-155]. The solvent contribution is not
      included in the reported mol-ecular weight and density. 

PMID- 24109306
TI  - 5-Chloro-3-ethyl-sulfinyl-2-(3-fluoro-phen-yl)-1-benzo-furan.
AB  - The asymmetric unit of the title compound, C16H12ClFO2S, contains two independent
      mol-ecules in which the benzo-furan ring systems are essentially planar, with
      r.m.s. deviations of 0.007 (1) and 0.013 (1) A. In the crystal, mol-ecules are
      linked by weak C-H?O hydrogen bonds into chains extending along the b axis. These
      chains are further packed into stacks along the c -axis by S?O contacts [3.1898
      (11) and 3.1361 (11) A] involving the sulfinyl groups. In both 3-fluoro-phenyl
      rings, the F atom is disordered over two positions, with site-occupancy factors
      of 0.921 (2) and 0.079 (2). 

PMID- 24109307
TI  - 5-Fluoro-N'-(4-methyl-cyclo-hexyl-idene)-3-phenyl-1H-indole-2-carbohydrazide.
AB  - The title compound, C22H22FN3O, crystallized with two independent mol-ecules (A
      and B) in the asymmetric unit; these are linked by a pair of N-H?O hydrogen
      bonds, forming a pseudo-centrosymmetric dimer with an R (2) 2(10) motif. In
      addition, a number of C-H?pi inter-actions are also observed. The 1H-indole ring
      systems in mol-ecules A and B are essentially planar [maximum deviations of 0.019
      (2) and 0.014 (2) A, respectively] and make dihedral angles of 77.64 (10) and
      69.50 (9) degrees , respectively, with thephenyl rings. 

PMID- 24109308
TI  - 5-Chloro-2-(4-methyl-phen-yl)-3-methyl-sulfinyl-1-benzo-furan.
AB  - In the title compound, C16H13ClO2S, the dihedral angle between the mean plane
      [r.m.s. deviation = 0.004 (2) A] of the benzo-furan ring system and the 4-methyl
      phenyl ring is 29.25 (8) degrees . In the crystal, inversion dimers linked by
      pairs of weak C-H?O interactions generate R 2 (2)(14) loops. 

PMID- 24109309
TI  - Methyl 3'-benzyl-4'-(2-chloro-phen-yl)-1'-methyl-2-oxo-spiro-[indoline-3,2'
      pyrrolidine]-3'-carboxyl-ate.
AB  - In the title compound, C27H25ClN2O3, the methyl-pyrrolidine ring adopts an
      envelope conformation with the N atom at the flap. The mean plane of the
      pyrrolidine ring makes dihedral angles of 82.1 (1), 84.4 (1) and 79.8 (1) degrees
      , respectively, with the adjacent benzene ring, the mean plane of the indoline
      ring system and the phenyl ring. The mol-ecular structure is stabilized by intra
      molecular C-H?O hydrogen bonds. In the crystal, mol-ecules are linked into chains
      along [101] by N-H?O hydrogen bonds. C-H?pi inter-actions are observed between
      the chains. 

PMID- 24109310
TI  - 2-Chloro-N-(3-meth-oxy-benzo-yl)benzene-sulfonamide.
AB  - In the title compound, C14H12ClNO4S, the dihedral angle between the chloro- and
      meth-oxy-substituted benzene rings is 87.40 (1) degrees . In the crystal,
      adjacent mol-ecules form inversion-related dimers through strong N-H?O hydrogen
      bonds, generating R 2 (2)(8) loops. The dimers are further connected through two
      C-H?O inter-actions that form C(11) chains and R 2 (2)(14) loops. Aromatic pi-pi
      stacking inter-actions [centroid-centroid separation = 3.8574 (1) A] are also
      observed. 

PMID- 24109311
TI  - Bis(1,3-dimethyl-1H-imidazolium) hexa-fluoro-silicate methanol 0.33-solvate.
AB  - The title compound, 6C5H9N2 (+).3SiF6 (2-).CH3OH, (I), was prepared by
      recrystallization of the crude salt from methanol along with solvent-free 2C5H9N2
      (+).SiF6 (2-) (II). Crystals of these solvatomorphs can be separated manually.
      The solvate (I) crystallizes in a rare hexa-gonal space group P6/mcc. Its
      asymmetric unit comprises one half of an imidazolium cation bis-ected by the
      crystallographic m-plane, one-sixth and one-twelfth of two crystallographically
      independent SiF6 (2-) dianions (Si atoms are located on the 3.2 and 6/m inversion
      centres), and one-twelfth of a methanol mol-ecule (C atoms are situated on the
      622 inversion centres, other atoms are disordered between general positions). In
      (I), all F atoms of 3.2-located SiF6 (2-) dianions participate in the formation
      of symmetry-equivalent contacts to the H atoms of imidazolium fragments, thus
      forming rod-type ensembles positioned on the -6 axes. These 'pillar' rods are, in
      turn, F?H inter-linked through SiF6 (2-) dianions disordered around the 6/m
      centres. The twelvefold disordered methanol mol-ecules are appended to this array
      by O-H?F hydrogen bonds to the 6/m located SiF6 (2-) dianions. In terms of graph
      set notation, the first and second level networks in (I) are N 1 = C 2 (2)(7)[3R
      4 (4)(14)]D 2 (2)(4) and N 2 = D 2 (2)(5) (C-H?O hydrogen bonds are not
      considered). After locating all symmetrically independent atoms in the cation and
      anions, there remained a strong (> 3 e A(-3)) residual electron density peak
      located at the 622 inversion centre. Treatment of this pre-refined model with the
      SQUEEZE procedure in PLATON [Spek (2009). Acta Cryst. D65, 148-155] revealed two
      voids per unit cell, indicative of the presence of the solvent methanol mol-ecule
      disordered about the 622 inversion centre. 

PMID- 24109312
TI  - Bis(1,3-dimethyl-1H-imidazolium) hexa-fluoro-silicate: the second monoclinic
      polymorph.
AB  - The title compound, 2C5H9N2 (+).SiF6 (2-), (I), crystallized as a new polymorph,
      different from the previously reported one (Ia) [Light et al. (2007 ?) private
      communication (refcode: NIQFAV). CCDC, Cambridge, England]. The symmetry [space
      groups P21/n for (I) and C2/c for(Ia)] and crystal packing patterns are markedly
      different for this pair of polymorphs. In (I), all imidazolium cations in the
      lattice are nearly parallel to each other, whereas a herringbone arrangement can
      be found in (Ia). In (I), each SiF6 (2-) dianion forms four short C-H?F contacts
      with adjacent C5H9N2 (+) cations, resulting in the formation of layers parallel
      to the ac plane. In (Ia), the C-H?F contacts are generally longer and result in
      the formation of layers along the bc plane. 

PMID- 24109313
TI  - 1-(2-Chloro-phen-yl)-3-(2-ethyl-hexa-noyl)thio-urea.
AB  - In the title compound, C15H21ClN2OS, the central chromophore moiety (C2N2OS) is
      approximately planar, with a maximum deviation of -0.027 (1) A, and is oriented
      at a dihedral angle of 86.7 (1) degrees  with respect to the chloro-phenyl ring.
      An intra-molecular N-H?O hydrogen bond stabilizes the mol-ecular conformation. In
      the crystal, mol-ecules associate via N-H?S hydrogen bonds, forming inversion
      dimers with motif R 2 (2)(8). These dimers are further connected by N-H?O
      hydrogen bonds, forming R 2 (2)(12) dimers. As a result, hydrogen-bonded chains
      running along [110] are formed. C-H?S inter-actions also occur. The terminal two
      C atoms of the butyl chain are disordered over two positions with an occupancy
      ratio of 0.54:0.46. 

PMID- 24109314
TI  - 2,2'-{[2-(2-Chloro-phen-yl)-4-methyl-imidazolidine-1,3-di-yl]bis-(methyl
      ene)}diphenol.
AB  - In the title compound, C24H25ClN2O2, the 2-hy-droxy-benzyl substituents and the 2
      chloro-phenyl group occupy the sterically preferred equatorial positions, whereas
      the methyl group occupies the axial position. The imidazolidine ring adopts an
      envelope conformation with one of the N atoms adjacent to the methylene group as
      the flap. The chloro-phenyl substit-uent approaches a nearly perpendicular
      orientation relative to the mean plane of the imidazolidine ring, making a
      dihedral angle of 73.44 (12) degrees  and the Cl atom is almost coplanar with the
      C atom bearing the chloro-phenyl substituent [Cl-C-C-C torsion angle = 1.1 (3)
      degrees ]. The hy-droxy-benzyl groups make dihedral angles of 71.23 (15) and
      69.13 (19) degrees  with the mean plane of the heterocyclic ring. The dihedral
      angle between the two hy-droxy-benzyl groups is 69.61 (12) degrees . The mol
      ecular structure features two intra-molecular O-H?N hydrogen bonds with graph-set
      motif S(6) between the phenolic hydroxyl groups and N atoms. 

PMID- 24109315
TI  - (Z)-Ethyl 2-cyano-3-(1H-imidazol-2-yl)acrylate.
AB  - The crystal structure of the title compound, C9H9N3O2, features N-H?N and C-H?O
      inter-actions. The N-H?N inter-action generates a chain running along the a axis
      and the C-H?O inter-action generates a chain along the c axis. An intra-molecular
      C-H?O inter-action is also observed. 

PMID- 24109316
TI  - 2,3-Tri-methyl-ene-7,8-di-hydro-pyrrolo-[1,2-a]thieno[2,3-d]pyrimidin-4(6H)-one.
AB  - The title mol-ecule, C12H12N2OS, is planar, with an r.m.s. deviation of 0.04 A.
      In the crystal, the N atom adjacent to the carbonyl group is sp (2)-hybridized.
      The crystal structure is stabilized by pi-pi stacking inter-actions observed
      between thio-phene and pyrimidinone rings of c-glide-related mol-ecules [centroid
      centroid distance = 3.9554 (13) A] and by C-H?pi inter-actions, forming an
      infinite chain along the c-axis direction. 

PMID- 24109317
TI  - 3-[(E)-(Benzyl-iminiumyl)meth-yl]-6,8-di-chloro-2H-chromen-4-olate.
AB  - In the title compound, C17H13Cl2NO2, the H atom of the -OH group is transferred
      to the N atom of the imine, forming a zwitterion. Thus, there is a intra
      molecular O?H-N, rather than O-H?N, hydrogen bond, which forms a six-membered
      ring. 

PMID- 24109318
TI  - (E)-6,8-Di-chloro-3-{[(naphthalen-1-ylmeth-yl)iminiumyl]meth-yl}-2H-chromen-4
      olate.
AB  - In the title compound, C21H15Cl2NO2, the H atom of the -OH group is transferred
      to the N atom of the imine, forming a zwitterion. Thus, there is formation of a
      six-membered ring via an intra-molecular O?H-N, rather than O-H?N, hydrogen bond
      in the mol-ecule. The dihedral angle between the naphthalene ring system and the
      benzene ring of the 2H-chromen system is 87.41 (4) degrees . In the crystal, the
      mol-ecules are packed through N-H?O, pi-pi [centroid-centroid distances = 3.744
      (3) and 3.780 (3) A], C-Cl?pi [Cl?centroid = 3.261 (3) A], C-H?pi and C-H?O inter
      actions. 

PMID- 24109319
TI  - 3-(4-Amino-phen-yl)-5-(4-meth-oxy-phen-yl)-4,5-di-hydro-1H-pyrazole-1-carbo-thio
      amide.
AB  - In the mol-ecule of title pyrazoline derivative, C17H18N4OS, the pyrazole ring
      adopts an envelope conformation with the flap atom, which bears the meth-oxy
      phenyl substituent, displaced by 0.0750 (12) A from the plane through the other
      ring atoms. The two substituted benzene rings make a dihedral angle of 70.59 (6)
      degrees . The meth-oxy group is twisted slightly with respect to the attached
      benzene ring [Cmeth-yl-O-C-C torsion angle = -8.84 (15) degrees ]. An intra
      molecular N-H?N hydrogen bond occurs. In the crystal, the pyrazoline mol-ecules
      are linked by N-H?O and N-H?S hydrogen bonds into zigzag layers parallel to the
      bc plane and stacked along the a axis by pi-pi inter-actions with centroid
      centroid distances of 3.4690 (7) and 3.5792 (7) A. C-H?pi inter-actions are also
      present. 

PMID- 24109320
TI  - 5-Fluoro-N-(2-methyl-3-oxo-1-thia-4-aza-spiro-[4.5]dec-4-yl)-3-phenyl-1H-indole-2
      carboxamide.
AB  - In the title compound, C24H24FN3O2S, the 1,3-thia-zolidine ring adopts an
      envelope conformation with the S atom as the flap, while the cyclo-hexane ring is
      in a chair conformation. In the crystal, mol-ecules are linked by N-H?O and C-H?F
      hydrogen bonds, forming a three-dimensional network. The unit cell contains six
      voids of 57 A(3), but the residual electron density (highest peak = 0.23 e A(-3)
      and deepest hole = -0.19 e A(-3)) in the difference Fourier map suggests no
      solvent mol-ecule occupies this void. 

PMID- 24109321
TI  - N-Butanoyl-N-(3-chloro-1,4-dioxonaph-thalen-2-yl)butanamide.
AB  - In the title compound, C18H18ClNO4, the imide group with its two alkyl
      substituents is approximately perpendicular to the plane of the naphtho-quinone
      ring system [dihedral angle = 78.5 (1) degrees ]. Further, the imide carbonyl
      groups are oriented in an anti sense. In the crystal, the substituted naphtho
      quinone rings form pi-pi stacks in the a-axis direction [perpendicular centroid
      centroid distance = 3.209 (2) A and slippage = 4.401 A]. 

PMID- 24109322
TI  - Ethyl (Z)-4'-(4-eth-oxy-1-hy-droxy-3,4-dioxobut-1-en-1-yl)-[1,1'-biphen-yl]-3
      carboxyl-ate.
AB  - The 1,3-diketone group of the title compound, C21H20O6, exists in a keto-enol
      form stabilized by a strong intra-molecular O-H?O hydrogen bond. As a result, a
      planar (mean deviation = 0.0099 A) six-membered hydrogen-bonded ring is formed.
      The C-O and C-C bond lengths suggest significant electron delocalization in the
      ring. The dihedral angle between the six-membered hydrogen-bonded ring and its
      adjacent benzene ring is 8.78 (5) degrees  and that between the benzene rings is
      19.70 (5) degrees . In the crystal, mol-ecules are packed in a layered structure
      parallel to the b axis through C-H?O and pi-pi inter-actions [centroid-centroid
      distance between stacked benzene rings = 3.868 (2) A]. 

PMID- 24109323
TI  - N-(3-Meth-oxy-benzo-yl)-2-methyl-benzene-sulfonamide.
AB  - In the title compound, C15H15NO4S, the dihedral angle between the methyl- and
      meth-oxy-substituted benzene rings is 88.99 (12) degrees . An intra-molecular C
      H?O hydrogen bond occurs. In the crystal, adjacent mol-ecules form inversion
      related dimers through strong N-H?O hydrogen bonds, generating R 2 (2)(8) loops.
      The dimers are further connected through C-H?O inter-actions that form C(8)
      chains parallel to (001). Mol-ecules are also connected through other C-H?O
      hydrogen bonds along the b axis, forming additional C(8) chains. Two aromatic pi
      pi stacking inter-actions [centroid-centroid separations = 3.6150 (1) and 3.6837
      (1) A] generate a three-dimensional architecture. 

PMID- 24109324
TI  - 5-[(4-Benzyl-1H-1,2,3-triazol-1-yl)meth-yl]-5H-dibenzo[b,f]azepine.
AB  - In the title compound, C24H20N4, the azepine ring adopts a boat conformation and
      the dihedral angle between the benzene rings fused to it is 57.95 (8) degrees .
      The bond-angle sum at the azepine N atom is 346.6 degrees , indicating a
      significant deviation from planarity. The triazole ring subtends a dihedral angle
      of 71.45 (10) degrees  with the terminal phenyl group. A weak intra-molecular C
      H?Na (a = azepine) inter-action occurs, which closes an S(6) ring. 

PMID- 24109325
TI  - 4-Fluoro-N-[(E)-3,4,5-tri-meth-oxy-benzyl-idene]aniline.
AB  - The title compound, C16H16FNO3, exists in a trans configuration with respect to
      the C=N bond [1.258 (2) A]. The central meth-oxy O atom deviates from the plane
      of the attached benzene ring by 0.0911 (14) A. The dihedral angle between the
      aromatic rings is 47.58 (11) degrees . The crystal structure features C-H?N and C
      H?O inter-actions. 

PMID- 24109326
TI  - 2-Amino-4,6-di-methyl-pyrimidine-sorbic acid (1/1).
AB  - In the crystal of the title compound, C6H9N3.C6H8O2, the 2-amino-4,6-di-methyl
      pyrimidine and sorbic acid mol-ecules are linked through N-H?O and O-H?N hydrogen
      bonds, which generate a cyclic bimolecular heterosynthon with an R 2 (2)(8) graph
      set motif. Further, two inversion-related pyrimidine mol-ecules are base-paired
      via a pair of N-H?N hydrogen bonds, forming a cyclic bimolecular homosynthon with
      a graph-set of R 2 (2)(8). A discrete hetero tetra-meric supra-molecular unit
      along the b axis is formed by the fusion of two heterosynthons and one
      homosynthon. An aromatic pi-pi inter-action [centroid-centroid distance = 3.7945
      (16) A] is observed between these tetra-meric units. 

PMID- 24109327
TI  - 4-Sulfamoylanilinium perchlorate.
AB  - In the crystal of the title salt, C6H9N2O2S(+).ClO4 (-), the components are
      linked by N-H?O hydrogen bonds, forming a three-dimensional network. The cations
      are connected along a and b axes, leading to linear and zigzag C(3) and C(8)
      chain motifs, respectively. A cation-anion inter-action along the c axis leads to
      a C 2 (2)(12) chain motif. R 3 (3)(18) and R 3 (3)(20) ring motifs are observed
      as cation-anion-type inter-actions. These hydrogen-bonding ring and chain motifs
      are localized at z = 0 or 1, leading to alternate hydro-philic and hydro-phobic
      regions along the c axis as a result of the stacking of anions and the aromatic
      cationic parts. 

PMID- 24109328
TI  - Tenulin 0.25-hydrate, a sesquiterpene lactone isolated from Helenium amarum.
AB  - The asymmetric unit of the title compound, C17H22O5.0.25H2O [systematic name: 2
      hy-droxy-2,2a,6,9a-tetra-methyl-2a,4a,5,6,6a,9a,9b,9c-octa-hydro-2H-1,4-dioxadi
      cyclo-pent[cd,f]azulene-3,9-dione 0.25-hydrate], a natural product isolated from
      Helenium amarum, contains two independent tenulin mol-ecules and half a water mol
      ecule of crystallization situated on a twofold rotation axis. The hy-droxy group
      of the hemiketal moiety is in a beta-position. In the crystal, each water mol
      ecule inter-acts with four tenulin mol-ecules via O-H?O hydrogen bonds. The two
      independent tenulin mol-ecules (A and B) differ only in the character of their
      participation in hydrogen bonding. Specifically, while A is an acceptor of Owater
      H?O A and a donor of O A -H?O B hydrogen bonds, mol-ecule B is an acceptor of the
      latter hydrogen bond and the donor of an O B -H?Owater hydrogen bond. In the
      crystal, these O-H?O hydrogen bonds link the tenulin and water mol-ecules into
      layers parallel to the ac plane. 

PMID- 24109329
TI  - Ethyl 3-(4-chloro-phen-yl)-2-phenyl-3-(4-phenyl-1,2,3-selena-diazol-5-yl)propano
      ate.
AB  - In the title compound, C25H21ClN2O2Se, the selena-diazole ring is almost planar
      [maximum deviation = 0.004 (2) A], and the adjacent benzene ring is twisted by
      50.6 (1) degrees  with respect to this ring. 

PMID- 24109330
TI  - 2-[(2-Chloro-phen-yl)(hy-droxy)meth-yl]phenol.
AB  - In the title compound, C13H11ClO2, the dihedral angle between the mean planes of
      the 2-chloro-phenyl and phenol rings is 87.4 (9) degrees . The methyl hy-droxy
      group lies nearly perpendicular to the plane of its attached benzene ring [O-C-C
      C torsion angle = 84.3 (3) degrees ]. The two hy-droxy groups lie on the same
      side of the mol-ecule and are in a slightly twisted gauche conformation [O-C-C-O
      torsion angle = 77.1 (8) degrees ] to each other. In the crystal, O-H?O hydrogen
      bonds between nearby methyl-hydroxy groups form dimers in alternating pairs
      aligned diagonally along the b axis. A view along the c axis reveals a hexa-meric
      aggregate mediated by a ring of six O-H?O hydrogen bonds generating an R 6
      (6)(12) motif loop. 

PMID- 24109331
TI  - 1,4-Bis(2-diazo-acet-yl)piperazine.
AB  - The asymmetric unit of the title compound, C8H10N6O2, contains one-half mol
      ecule, which is completed by a crystallographic center of symmetry. The
      piperazine ring adopts a chair conformation. In the crystal, weak C-H?O inter
      actions link the mol-ecules into layers parallel to the bc plane. The crystal
      packing also exhibits short N?N contacts of 3.0467 (16) A between the terminal
      diazo N atoms from neighbouring mol-ecules. 

PMID- 24109332
TI  - Ethyl 2-(5-meth-oxy-2-methyl-1H-indol-3-yl)acetate.
AB  - In the title compound, C14H17NO3, the nine-membered 1H-indole ring system is
      essentially planar [maximum deviation = 0.019 (1) A]. In the crystal, mol-ecules
      are linked via N-H?O hydrogen bonds, forming chains along [001]. These chains are
      linked via C-H?O hydrogen bonds and C-H?pi inter-actions, forming a two
      dimensional network lying parallel to the ac plane. 

PMID- 24109333
TI  - 2-(4-Chloro-phen-yl)-1-pentyl-4,5-di-phenyl-1H-imidazole.
AB  - In the title compound, C26H25ClN2, the phenyl rings and the 2-(4-chloro-phen-yl)
      group make dihedral angles of 30.03 (11), 67.49 (12) and 41.56 (11) degrees ,
      respectively, with the imidazole ring. In the crystal, the mol-ecules inter-act
      with each other via very weak C-H?pi contacts, forming layers parallel to (110). 

PMID- 24109334
TI  - Ethyl 3-amino-5-anilino-4-cyano-thio-phene-2-carboxyl-ate.
AB  - In the title compound, C14H13N3O2S, the dihedral angle between the thio-phene and
      phenyl rings is 24.95 (8) degrees . The mol-ecular structure is consolidated by
      intra-molecular N-H?O and C-H?S inter-actions. The crystal structure features N
      H?N and N-H?O hydrogen bonds forming centrosymmetric R 2 (2)(12) dimers, which
      are linked into a two-dimensional network parallel to (011) with an S(6)R 2 (2)
      S(6) motif. In addition, pi-pi stacking inter-actions [centroid-centroid distance
      = 3.7013 (12) A] occur between the thio-phene and phenyl rings of adjacent mol
      ecules. 

PMID- 24109335
TI  - 2-Bromo-5-fluoro-benzaldehyde.
AB  - In the title compound, C7H4BrFO, the benzaldehyde O atom is found to be trans to
      the 2-bromo substituent. In the crystal, short Br?F inter-actions between the
      bromine and fluorine substituents are observed at distances of 3.1878 (14),
      3.3641 (13) and 3.3675 (14) A. Offset face-to-face pi-stacking inter-actions are
      also observed for both of the independent mol-ecules in the asymmetric unit
      running parallel to the crystallographic b axis, characterized by centroid
      centroid distances of 3.8699 (2) and 3.8699 (2) A. 

PMID- 24109336
TI  - 7-Benzyl-3-methyl-6-phenyl-imidazo[2,1-b][1,3]thia-zol-7-ium chloride 0.75
      hydrate.
AB  - Theasymmetric unit of the title salt, C19H17N2S(+).Cl(-).0.75H2O, contains two
      symmetrically independent formula units of the carbenium salt along with three
      water mol-ecules. The water mol-ecules are only 50% occupated, and one of them is
      positioned in a hydro-phobic pocket not forming any hydrogen bonds. The
      conformation of the independent cations is very similar, with dihedral angles of
      61.0 (2) and 61.5 (3) degrees  between the benzene rings. They form quasi
      centrosymmetric couples via pi-pi stacking inter-actions between the benzene and
      imidazo[2,1-b]thia-zole rings [centroid-centroid distances = 3.718 (3) and 3.663
      (3) A]. In the crystal, O-H?Cl hydrogen bonds lead to the formation of a helical
      anion-water chain along the c-axis direction. The cations connect to the anion
      water chain through C-H?Cl inter-actions, generating a three-dimensional supra
      molecular network. O-H?S hydrogen bonds and C-H?O inter-actions also occur. 

PMID- 24109337
TI  - N'-(2,4-Di-nitro-phen-yl)acetohydrazide monohydrate.
AB  - In the crystal structure of the title compound, C8H8N4O5.H2O, the organic and
      lattice water mol-ecules are linked together via N-H?O and O-H?O hydrogen bonds.
      A C-H?O inter-action is also observed between the organic mol-ecules. These
      hydrogen bonds and inter-actions lead to the formation of a three-dimensional
      network. An intra-molecular N-H?O hydrogen bond also occurs. The dihedral angle
      between the acetyl group and the almost planar hydrazide moiety [maximum
      deviation from the least-squares plane is 0.209 (2) A for one of the nitro O
      atoms] is 88.5 (3) degrees . 

PMID- 24109338
TI  - (E)-1-[(2,4,6-Tri-bromo-phen-yl)diazen-yl]naphthalen-2-ol.
AB  - The title azo mol-ecule, C16H9Br3N2O, adopts a trans conformation with respect to
      the azo N=N double bond. An intra-molecular O-H?N hydrogen bond forms an S(6)
      ring motif. The dihedral angle between the naphthalene ring system and the
      benzene ring is 33.80 (16) degrees . In the crystal, mol-ecules are stacked in
      columns along the a axis by pi-pi inter-actions [centroid-centroid distances =
      3.815 (3) and 3.990 (3) A]. 

PMID- 24109339
TI  - 1-(5-Bromo-2-oxoindolin-3-yl-idene)thio-semicarbazone.
AB  - The title mol-ecule, C9H7BrN4OS, is essentially planar [r.m.s. deviation = 0.066
      (2) A], the maximum deviation from the mean plane through the non-H atoms being
      0.190 (3) A for the terminal amine N atom. In the crystal, mol-ecules are linked
      through N-H?O and N-H?S inter-actions, generating infinite chains along the b
      axis direction. In turn, the chains are stacked along the a axis via pi-pi inter
      actions [centroid-centroid distance = 3.470 (2) A] and further connected by N
      H?Br inter-actions into a three-dimensional network. An intra-molecular N-H?O
      hydrogen bond is also observed. 

PMID- 24109340
TI  - (Di-methyl-phosphor-yl)methanaminium iodide-(di-methyl-phosphor-yl)methan-amine
      (1/1).
AB  - The asymmetric unit of the title structure, C3H11NOP(+).I(-).C3H10NOP, consists
      of one (di-methyl-phosphor-yl)methanamine (dpma) mol-ecule, one (di-methyl
      phosphor-yl)methanaminium (dpmaH) ion and one iodide counter-anion. In the
      crystal, medium-strong to weak N-H?O and N-H?N hydrogen bonds connect dpmaH
      cations and dpma mol-ecules into strands along [001]. The iodide counter-anions
      form only very weak hydrogen bonds. The crystal used for the diffraction study
      was found to be an inversion twin with a ratio of 0.83 (2):0.17 (2). The title
      structure is isotypic to that of dpmaH[ClO4].dpma [Buhl et al. (2013 ?). Crystals
      3, 350-362]. 

PMID- 24109341
TI  - 2,2-Diphenyl-N-{[2-(tri-fluoro-meth-yl)phen-yl]carbamo-thio-yl}acetamide.
AB  - The title mol-ecule, C22H17F3N2OS, adopts a trans-cis conformation with respect
      to the positions of the carbonyl and tri-fluoro-methyl-benzene groups against the
      thio-carbonyl group across the C-N bonds. The mol-ecular structure is stabilized
      by an intra-molecular N-H?O hydrogen bond with an S(6) ring motif. The tri-fluoro
      methyl-substituted benzene ring forms dihedral angles of 66.05 (9) and 47.19 (9)
      degrees  with the terminal phenyl rings and is twisted from the O=C-N-(C=S)-N
      carbonyl-thio-urea plane [maximum deviation = 0.0535 (12) A], making a dihedral
      angle of 63.59 (8) degrees . In the crystal, N-H?O and C-H?F hydrogen bonds link
      the mol-ecules into a layer parallel to the bc plane. A C-H?pi inter-action is
      also observed. 

PMID- 24109342
TI  - Allyl 2-(2,2-dimethyl-3a,6a-di-hydro-furo[3,2-d][1,3]dioxol-5-yl)-4-oxo-4H
      chromene-3-carboxyl-ate.
AB  - In the title compound, C20H18O7, the dioxolane ring adopts an envelope
      conformation with the dimethyl-substituted C atom as the flap, and its mean plane
      makes a dihedral angle of 73.25 (2) degrees  with the pyran ring mean plane. The
      furan ring makes dihedral angles of 67.43 (12) and 6.20 (11) degrees  with the
      mean plane of the dioxolane and pyran rings, respectively. The O atom attached to
      the pyran ring deviates by 0.0219 (2) A from its mean plane. In the crystal, mol
      ecules are linked via C-H?O hydrogen bonds, forming chains along [010] and
      enclosing R 2 (2)(9) loops. They stack along the a axis with pi-pi inter-actions
      involving the 4H-chromene units [centroid-centroid distances of 3.6389 (13) and
      3.6555 (13) A]. The terminal CH2=CH- atoms of the allyl acetate group are
      disordered over two sets of sites with a refined occupancy ratio of 0.717
      (6):0.283 (6). 

PMID- 24109343
TI  - 4-Phenyl-1,2,4-tri-aza-spiro-[4.5]dec-1-ene-3-thione.
AB  - In the title compound, C13H15N3S, the 4,5-di-hydro-3H-1,2,4-triazole ring is
      nearly planar [maximum deviation = 0.020 (1) A], while the cyclo-hexane ring
      adopts a chair conformation. The dihedral angle between the 4,5-di-hydro-3H-1,2,4
      triazole ring and the phenyl ring is 74.68 (7) degrees . No specific inter
      molecular inter-actions are discerned in the crystal packing. 

PMID- 24109344
TI  - 2,2'-[Ethane-1,2-diylbis(-oxy)]dibenz-alde-hyde.
AB  - In the title compound, C16H14O4, the benzene rings are inclined at a dihedral
      angle of 75.14 (9) degrees . The torsion angle of the bridging O-C-C-O group is 
      76.50 (11) degrees . In the crystal, mol-ecules are linked by C-H?O hydrogen
      bonds, forming C(6) chains along [100]. Furthermore, C-H?pi inter-actions and pi
      pi stacking inter-actions [centroid-centroid distances = 3.6957 (7) and 3.6735
      (8) A] contribute to the stability of the crystal packing. 

PMID- 24109345
TI  - (1S,3S,8R,9S,11R)-10,10-Di-bromo-3,7,7,11-tetra-methyl-tetra-cyclo
      [6.5.0.0(1,3).0(9,11)]trideca-ne.
AB  - The title compound, C17H26Br2, was synthesized from beta-himachalene (3,5,5,9
      tetra-methyl-2,4a,5,6,7,8-hexa-hydro-1H-benzo-cyclo-heptene), which was isolated
      from the essential oil of the Atlas cedar (Cedrus Atlantica). The asymmetric unit
      contains two independent mol-ecules with similar conformations. Each mol-ecule is
      built up from fused six- and seven-membered rings and two appended three-membered
      rings. In both mol-ecules, the six-membered ring has a screw boat conformation,
      whereas the seven-membered ring displays a boat conformation. No specific inter
      molecular inter-actions were discerned in the crystal packing. 

PMID- 24109346
TI  - Methyl 5-(4-acet-oxy-phen-yl)-2-(2-bromo-benzyl-idine)-7-methyl-3-oxo-2,3-di
      hydro-5H-1,3-thia-zolo[3,2-a]pyrimidine-6-carboxyl-ate.
AB  - In the title mol-ecule, C24H19BrN2O5S, the pyrimidine ring is in a flattened half
      chair conformation and the 4-acet-oxy-phenyl group is substituted axially to this
      ring. The thia-zole ring is essentially planar [with a maximum deviation of 0.012
      (2) A for the N atom] and forms dihedral angles of 17.65 (13) and 88.95 (11)
      degrees  with the bromo- and acet-oxy-substituted benzene rings, respectively.
      The dihedral angle between the benzene rings is 81.84 (13) A. In the crystal,
      pairs of weak C-H?O hydrogen bonds lead to the formation of inversion dimers. A
      weak C-H?pi inter-action and pi-pi stacking inter-actions with centroid-centroid
      distances of 3.5903 (14) A are observed. 

PMID- 24109347
TI  - N-(3-Meth-oxy-benzo-yl)-4-methyl-benzene-sulfonamide.
AB  - In the title compound, C15H15NO4S, the dihedral angle between the benzene rings
      is 88.87 (1) degrees . In the crystal, adjacent mol-ecules form inversion dimers
      through pairs of strong N-H?O hydrogen bonds, generating R 2 (2)(8) loops. Two C
      H?pi inter-actions and an aromatic pi-pi inter-action [centroid-centroid
      separation = 3.8191 (1) A] are also observed. 

PMID- 24109348
TI  - Carbinoxaminium dipicrate.
AB  - In the dication of the title salt, C16H21ClN2O(2+).2C6H2N3O7 (-) [systematic
      name: 2-{(4-chloro-phen-yl)[2-(di-methyl-aza-nium-yl)eth-oxy]meth-yl}pyridinium
      bis-(2,4,6-tri-nitro-phenolate), contains a carbinoxaminium dication and two
      picrate anions, which are held together through inter-molecular N-H?O hydrogen
      bonds. In the dication, the two aromatic rings form a dihedral angle of 80.1 (1)
      degrees . In the two independent picrate anions, the nitro groups are twisted
      from the benzene plane, the largest dihedral angle in each ion being 42.8 (1) and
      81.1 (5) degrees . In the crystal, in addition to the classical N-H?O hydrogen
      bonds, weak C-H?O hydrogen bonds and pi-pi inter-actions between the aromatic
      rings of the anions [centroid-centroid distances of 3.5768 (15) and 3.7436 (15)
      A] help to establish the packing. 

PMID- 24109349
TI  - Bis(2,4,6-tri-amino-pyrimidin-1-ium) sulfate penta-hydrate.
AB  - The asymmetric unit of the title salt, 2C4H8N5 (+).SO4 (2-).5H2O, contains four
      2,4,6-tri-amino-pyrimidinium (TAPH(+)) cations, two sulfate anions and ten
      lattice water mol-ecules. Each two of the four TAPH(+) cations form dimers via N
      H?N hydrogen bonds between the amino groups and the unprotonated pyrimidine N
      atoms [graph-set motif R 2 (2)(8)]. The (TAPH(+))2 dimers, in turn, form slightly
      offset infinite pi-pi stacks parallel to [010], with centroid-centroid distances
      between pyrimidine rings of 3.5128 (15) and 3.6288 (16) A. Other amino H atoms,
      as well as the pyrimidinium N-H groups, are hydrogen-bonded to sulfate and
      lattice water O atoms. The SO4 (2-) anions and water mol-ecules are inter
      connected with each other via O-H?O hydrogen bonds. The combination of hydrogen
      bonding inter-actions and pi-pi stacking leads to the formation of a three
      dimensional network with alternating columns of TAPH(+) cations and channels
      filled with sulfate anions and water mol-ecules. One of the sulfate anions shows
      a minor disorder by a ca 37 degrees  rotation around one of the S-O bonds
      [occupancy ratio of the two sets of sites 0.927 (3):0.073 (3)]. One water mol
      ecule is disordered over two mutually exclusive positions with an occupancy ratio
      of 0.64 (7):0.36 (7). 

PMID- 24109350
TI  - N'-(3-Sulfanyl-idene-3,4-di-hydro-quinoxalin-2-yl)benzohydrazide di-methyl
      formamide monosolvate.
AB  - The 2-sulfanyl-idene-3,4-di-hydro-quinoxalin-2-yl ring system of the title
      solvate, C15H12N4OS.C3H7NO, is essentially planar, the maximum deviation from the
      mean plane being 0.024 (2) A for the thione C atom. The mean plane through the
      fused-ring system is almost perpendicular to the terminal phenyl ring, as
      indicated by the dihedral angle of 70.05 (8) degrees . In the crystal, the main
      and solvent mol-ecules are linked by N-H?O hydrogen bonds, forming a layer
      parallel to (010). 

PMID- 24109351
TI  - Ethyl 1,4-bis-(4-chloro-phen-yl)-2-methyl-1H-pyrrole-3-carboxyl-ate.
AB  - In the title mol-ecule, C20H17Cl2NO2, the pyrrole moiety makes dihedral angles of
      63.42 (11) and 70.43 (12) degrees  with the chlorobenzene rings. The eth-oxy
      carbonyl unit is present in a synperiplanar conformation with respect to the
      pyrrole ring, as indicated by the dihedral angle of 14.5 (3) degrees . In the
      crystal, mol-ecules are linked into chains parallel to the a-axis direction by
      weak C-H?O hydrogen bonds. 

PMID- 24109352
TI  - (2S,3S)-3-(3-Bromo-phen-yl)-6,6-dimethyl-2-nitro-2,3,6,7-tetra-hydro-benzo-furan
      4(5H)-one.
AB  - The title compound, C16H16BrNO4, has two adjacent chiral C atoms and both have an
      S configuration. The fused cyclo-hex-2-enone and di-hydro-furan rings both adopt
      envelope conformations, with the quaternary C atom and the nitro-substituted C
      atoms as the respective flap. The flap atoms lie 0.607 (3) and -0.253 (2) A,
      respectively, from the mean plane of the remaining ring atoms on opposite sides.
      The dihedral angle between the mean plane of the four coplanar atoms of the di
      hydro-furan ring and the phenyl ring is 86.16 (3) degrees . In the crystal, mol
      ecules are linked by weak C-H?O inter-actions, forming a ladder motif parallel to
      the b axis. 

PMID- 24109353
TI  - (Z)-3-Methyl-4-[1-(4-methyl-anilino)propyl-idene]-1-phenyl-1H-pyrazol-5(4H)-one.
AB  - In the title mol-ecule, C20H21N3O, the central pyrazole ring forms dihedral
      angles of 4.75 (9) and 49.11 (9) degrees , respectively, with the phenyl and
      methyl-substituted benzene rings. The dihedral angle between the phenyl and
      benzene rings is 51.76 (8) degrees . The amino group and carbonyl O atom are
      involved in an intra-molecular N-H?O hydrogen bond. In the crystal, pi-pi inter
      actions are observed between benzene rings [centroid-centroid seperation = 3.892
      (2) A] and pyrazole rings [centroid-centroid seperation = 3.626 (2) A], forming
      chains along [111]. The H atoms of the methyl group on the p-tolyl substituent
      were refined as disordered over two sets of sites in a 0.60 (4):0.40 (4) ratio. 

PMID- 24109354
TI  - 3,4-Di-methyl-thieno[2,3-b]thio-phene-2,5-dicarbo-nitrile.
AB  - The asymmetric unit of the title compound, C10H6N2S2, contains two
      crystallographically independent but conformationally similar mol-ecules. The
      fused thio-phene ring cores are almost planar [maximum deviation = 0.027 (3) A]
      with the thio-phene rings forming dihedral angles of 0.5 (4) degrees  in one mol
      ecule and 1.91 (4) degrees  in the other. The crystal packing is stabilized only
      by van der Waals inter-actions. 

PMID- 24109355
TI  - 2-[(1,3-Benzo-thia-zol-2-yl)imino-meth-yl]-6-meth-oxy-phenol: a new monoclinic
      polymorph.
AB  - The title compound, C15H12N2O2S, is a P21/c polymorph of a previously reported
      P21/n polymorph [Buyukgungor et al. (2004 ?). Acta Cryst. E60, o1414-o1416]. The
      dihedral angle between the benzo-thia-zole (r.m.s. deviation = 0.010 A) and the
      benzene ring of 7.86 (6) degrees  compares with 10.76 (10) degrees  in the
      literature structure. The meth-oxy substituent is almost coplanar with the
      benzene ring to which it is attached [C-O-C-C torsion angle = 178.31 (14) degrees
      ] and the conformation about the imine bond [1.287 (2) A] is E. There is an intra
      molecular O-H?N hydrogen bond and the hy-droxy O and thio-ether S atoms are syn.
      In the crystal, columns are formed along the b axis as centrosymmetric dimeric
      aggregates, mediated by C-H?O inter-actions and linked by pi-pi inter-actions
      between the thia-zole and benzene rings [centroid-to-centroid distance = 3.8256
      (10) A]. 

PMID- 24109356
TI  - (2E)-3-(6-Chloro-2-meth-oxy-quinolin-3-yl)-1-(2,4-di-methyl-quinolin-3-yl)prop-2
      en-1-one.
AB  - The mol-ecule of the title compound, C24H19ClN2O2, is bent, with the dihedral
      angle between the terminal quinoline ring systems being 63.30 (5) degrees . The
      quinolinyl residues are connected by an almost planar prop-2-en-1-one bridge
      (r.m.s. deviation = 0.022 A), with the dihedral angles between this plane and the
      appended quinolinyl residues being 75.86 (7) and 38.54 (7) degrees . The C atom
      of the meth-oxy group is close to coplanar with its attached ring [deviation =
      0.116 (2) A]. In the crystal, a three-dimensional architecture is constructed by
      meth-yl-carbonyl C-H?O inter-actions and pi-pi inter-actions between
      centrosymmetrically related quinolinyl residues [centroid-to-centroid separations
      3.5341 (10) and 3.8719 (9) A]. 

PMID- 24109357
TI  - (2E)-3-(2-Chloro-8-methyl-quinolin-3-yl)-1-(2,4-di-methyl-quinolin-3-yl)prop-2-en
      1-one.
AB  - In the mol-ecule of the title compound, C24H19ClN2O, the terminal quinolinyl
      residues are close to perpendicular to each other [dihedral angle 83.72 (4)
      degrees ]. The quinolinyl residues are connected by and inclined to the prop-2-en
      1-one bridge, with the Car-Car-C-C (ar = aromatic) torsion angles being 71.01
      (17) and 20.6 (2) degrees . The crystal structure features phen-yl-carbonyl C-H?O
      inter-actions and pi-pi inter-actions between centrosymmetrically related
      quinolinyl residues [3.5341 (10) and 3.8719 (9) A], which together lead to a
      three-dimensional architecture. 

PMID- 24109358
TI  - [(4E)-1-Methyl-2,6-diphenyl-3-(propan-2-yl)piperidin-4-yl-idene]amino 3-methyl
      benzoate.
AB  - In the title compound, C29H32N2O2, the piperidine ring exists in a chair
      conformation (the bond-angle sum at the sp (2)-hybridized C atom is 359.79
      degrees ). The phenyl rings and the methyl group substituted on the heterocyclic
      ring are in equatorial orientations. In the crystal, pairs of C-H?pi inter
      actions result in the formation of inversion dimers. 

PMID- 24109359
TI  - 3-Hy-droxy-anilinium p-toluene-sulfonate.
AB  - The asymmetric unit of the title salt, C6H8NO(+).C7H7O3S(-), contains two cations
      and two anions. In the crystal, the cations and anions are linked through
      extensive N-H?O and O-H?O hydrogen-bonding inter-actions, which result in R 4
      (4)(18) and R 2 (1)(4) ring motifs, forming a three-dimensional network. 

PMID- 24109360
TI  - 1,4,8,11-Tetra-azonia-cyclo-tetra-decane tetra-kis-(hydrogensulfate).
AB  - In the title salt, C10H28N4 (4+).4HSO4 (-), the cation lies about an inversion
      center. In the crystal, O-H?O and N-H?O hydrogen bonds connect the anions and
      cations, forming a three-dimensional network. 

PMID- 24109361
TI  - 5-Amino-1H-1,2,4-triazol-4-ium hydrogen oxalate.
AB  - In the title salt, C2H5N4 (+).C2HO4 (-), the hydrogen oxalate anions form
      corrugated chains parallel to the c axis, linked by inter-molecular O-H?O
      hydrogen bonds. The 5-amino-1H-1,2,4-triazol-4-ium cations are connected into
      centrosymmetric clusters via weak C-H?N hydrogen bonds forming nine-membered
      rings with an R 3 (3)(9) motif. These clusters are inter-connected via anions
      through N-H?O hydrogen bonds, building a three-dimensional network. 

PMID- 24109362
TI  - N,N-Diethyl-4-[(E)-(pyridin-3-yl)diazen-yl]aniline.
AB  - The mol-ecule of the title compound, C15H18N4, adopts a trans conformation with
      respect to the diazo N=N bond. The dihedral angle between the benzene and
      pyridine rings in the mol-ecule is 8.03 (5) degrees . In the crystal, a weak C
      H?pi inter-action arranges the mol-ecules into a corrugated ribbon, with an anti
      parallel orientation of neighboring mol-ecules propagating in the [100]
      direction. 

PMID- 24109363
TI  - 2-Cyano-1-methyl-pyridinium iodide.
AB  - The cation in the title compound, C7H7N2 (+).I(-), is planar (r.m.s. deviation
      for the nine fitted non-H atoms = 0.040 A). The crystal packing is best described
      as undulating layers of cations and anions associated via C-H?I inter-actions. 

PMID- 24109364
TI  - 2-(10',10'-Dimethyl-3'-sulfanyl-idene-4'-aza-tri-cyclo-[5.2.1.0(1,5)]decan-2'-
      yl)-10,10-dimethyl-4-aza-tri-cyclo-[5.2.1.0(1,5)]decane-3-thione.
AB  - The title compound, C28H40N2O2S2, was obtained as a minor product from an anti
      aldol reaction between the corresponding N-propionyl-thiol-actam and
      benzaldehyde. The asymmetric unit contains one half-molecule, which is completed
      by inversion symmetry. The molecule displays a nearly eclipsed conformation along
      the central C-C bond with a C-C-C-C- torsion angle of 20.4 (3) degrees . 

PMID- 24109365
TI  - (1S,3R,8R,11S)-11-Bromo-10-bromo-methyl-2,2-di-chloro-3,7,7-tri-methyl-tricyclo
      [6.4.0.0(1,3)]dodec-9-ene.
AB  - The title compound, C16H22Br2Cl2, was synthesized from beta-him-achalene (3,5,5,9
      tetra-methyl-2,4a,5,6,7,8-hexa-hydro-1H-benzo-cyclo-heptene), which was isolated
      from the essential oil of the Atlas cedar (Cedrus Atlantica). The mol-ecule is
      built up from fused six- and seven-membered rings and an appended three-membered
      ring. The six-membered ring has a half-chair conformation, whereas the seven
      membered ring displays a chair conformation. The dihedral angle between the two
      best plane through each ring is 59.5 (2) degrees . No specific inter-molecular
      inter-actions were discerned in the crystal packing. 

PMID- 24109366
TI  - (2-tert-Butyl-3-phenyl-2,3-di-hydro-isoxazole-4,5-di-yl)bis-(phenyl-methanone).
AB  - The phenyl and tert-butyl groups of the title compound, C27H25NO3, exhibit a
      trans configuration in agreement with the stereochemistry of the Z phenyl-N-tert
      butyl-nitrone starting material. The attached carbonyl groups are not coplanar
      with the neighboring di-hydro-isoxazole ring and the phenyl rings they are bonded
      to, with torsion angles of 59.26 (8), 17.53 (11), 16.52 (12) and 52.86 (7)
      degrees . The dihedral angle between the di-hydro-isoxazole ring and the directly
      attached phenyl group is 86.86 (8) degrees . There are two nonclassical inter
      molecular C-H?O hydrogen-bonding inter-actions that operate together with an
      inter-molecular C-H?pi inter-action to form a supramolecular architecture in the
      crystal system. 

PMID- 24109367
TI  - 5-(4-Chloro-phen-yl)-7-(4-methyl-phen-yl)-4-(pyrrolidin-1-yl)-7H-pyrrolo-[2,3
      d]pyrimidine.
AB  - The title compound, C23H21ClN4, contains two molecules (A and B) in the
      asymmetric unit, which are related to one another by a pseudo-inversion center.
      The non-aromatic pyrrolidine ring in each independent mol-ecule adopts a half
      chair conformation; the ring puckering parameters are theta = 0.407 (3) A and phi
      = 270.5 (4) degrees , and the pseudo-rotation parameters are rho = 72.5 (3)
      degrees  and tau = 42.2 (2) degrees  for an N-C bond of molecule A, and the
      corresponding values are 0.415 (3) A, 271.6 (4) degrees , 73.6 (3) degrees  and
      42.6 (2) degrees  for molecule B. The dihedral angles between the central fused
      ring system and the substituted chlorophenyl and methylphenyl rings are 66.35 and
      45.59 degrees , respectively, for molecule A, and 64.51 and 41.89 degrees  for
      molecule B. The geometry of all four intramolecular C-H?pi interactions are of
      type III. pi-pi interactions involving the centroids of symmetry-related pyrrole
      rings of molecule B are 4.390 A, contributing further to the stability of the
      molecule. 

PMID- 24109368
TI  - 2-Cyano-anilinium iodide.
AB  - The solid-state structure of the title salt, C7H7N2 (+.)I(-), consists of cation
      anion sheets lying parallel to (110), with the components linked by N-H?I
      hydrogen bonds. 

PMID- 24109369
TI  - (E)-Benz-yl(1-phenyl-ethyl-idene)amine.
AB  - The title compound, C15H15N, represents an E isomer. The mol-ecule exhibits a
      minor [9.1 (2)%] disorder with methyl-benzyl-idene and benzyl groups inter
      changing their positions. The C=N bond length is 1.292 (2) A. The mol-ecular
      geometry is essentially planar, with the maximal twist of 8.5 (3) degrees  for
      the benzyl group. The herringbone packing arrangement does not exhibit any pi
      stacking inter-actions. 

PMID- 24109370
TI  - Isotenulin.
AB  - Isotenulin, C17H22O5, is a sesquiterpene lactone isolated from sneezeweed
      Helenium amarum. It crystallizes with two independent mol-ecules in the
      asymmetric unit. In each mol-ecule, two five-membered rings (cyclo-pentenone and
      lactone) are trans-fused to the central seven-membered ring. The five-membered
      rings each adopt envelope conformations. The seven-membered ring adopts a twist
      chair conformation. In the crystal, the molecules are linked by C-H?O
      interactions, which generate a three-dimensional network. 

PMID- 24109371
TI  - 5''-(2-Fluoro-benzyl-idene)-1'-(2-fluoro-phen-yl)-1''-methyl
      1',2',3',5',6',7',8',8a'-octa-hydro-dispiro-[ace-naphthyl-ene-1,3'-indolizine
      2',3''-piperidine]-2,4''(1H)-dione.
AB  - In the title compound, C37H32F2N2O2, the central six-membered piperidine ring
      adopts a twisted half-chair conformation, with the N and methyl-ene C atoms
      deviating by -0.2875 (16) and 0.4965 (15) A, respectively, from the mean plane
      defined by the other four atoms. The piperidine connected to the octa-hydro
      indolizine ring is in a half-chair conformation. The five-membered pyrrole ring
      adopts a slightly twisted envelope conformation with the piperidine C atom as the
      flap atom. The F and H atoms of both fluoro-benzene rings are disordered, with
      occupancy factors of 0.941 (3):0.059 (3) and 0.863 (3):0.137 (3). The mol-ecular
      structure features some intra-molecular C-H?O inter-actions. In the crystal, a
      supra-molecular zigzag chain sustained by C-H?F inter-actions parallel to the c
      axis is formed, generating a C(12) graph-set motif. 

PMID- 24109372
TI  - 1-(4-Meth-oxy-phen-yl)-2-[4-(tri-fluoro-meth-yl)phen-yl]-1H-phenanthro[9,10
      d]imidazole.
AB  - In the title compound, C29H19F3N2O, a phenanthroline-fused imidazole tetra-cyclic
      system, the fused benzene rings deviate slightly from the central ring and make
      dihedral angles with this ring of 3.47 (8) and 3.05 (8) degrees . The tri-fluoro
      methyl-phenyl ring is roughly coplanar with the phenanthroline-fused imidazole
      tetra-cyclic system [dihedral angle = 11.02 (6) degrees ], while the meth-oxy
      phenyl ring is almost perpendicular [dihedral angle = 87.65 (6) degrees ]. There
      are intra-molecular C-H ?pi inter-actions involving the meth-oxy-phenyl ring and
      the central phenanthroline ring, as well as an inter-molecular C-H?pi inter
      action involving the phenanthroline ring. In addition, there is an inter
      molecular pi-pi inter-action involving the central phenanthroline ring and the
      tri-fluoro-methyl-phenyl ring [centroid-centroid distance = 3.685 (2) A], as well
      as C-H?N inter-actions linking the mol-ecules into dimers. 

PMID- 24109373
TI  - 2,2'-{[2-(2-Hy-droxy-phen-yl)-4-methyl-imidazolidine-1,3-di-yl]bis-(methyl
      ene)}diphenol.
AB  - The asymmetric unit in the title compound, C24H26N2O3, comprises two independent
      mol-ecules (A and B). In molecule A, the central 2-hydroxyphenyl ring is inclined
      to the mean plane of the major component of the imidazolidine ring by 84.52 (14)
      degrees , and by 68.08 (9) and 47.48 (9) degrees  to the outer phenol rings. The
      later are inclined to one another by 66.76 (9) degrees  and by 78.12 (14) and
      80.20 (14) degrees  to the imidazoline ring mean plane. In molecule B, the
      central 2-hydroxyphenyl ring is inclined to the mean plane of the imidazolidine
      ring by 73.64 (10) degrees , and by 75.60 (8) and 38.32 (9) degrees  to the outer
      phenol rings. The later are inclined to one another by 69.47 (9) degrees  and by
      82.60 (10) and 64.26 (10) degrees  to the imidazolidine ring mean plane. In each
      of the independent mol-ecules, two intra-molecular O-H?N hydrogen bond form S(6)
      ring motifs. In disordered mol-ecule A, the O-H groups of the 2-hy-droxy-benzyl
      groups are also involved in intra-molecular O-H?O hydrogen bonds, with the O atom
      of the hy-droxy-phenyl group acting as the acceptor. In the crystal, A molecules
      are linked by pairs of O-H?O hydrogen bonds forming inversion dimers. These
      dimers are linked to the B molecules via O-H?O hydrogen bonds forming double
      layered slabs lying parallel to the bc plane. 

PMID- 24109375
TI  - N-tert-But-oxy-carbonyl-alpha-(2-fluoro-benzyl)-l-proline.
AB  - In the title compound, C17H22FNO4, the pyrrolidine ring adopts an envelope
      conformation with the disordered com-ponents of the methylene C atom, with site
      occupancies of 0.896 (7) and 0.104 (7), being the flap on either side of the mean
      plane involving the other atoms of the ring. The carb-oxy-lic acid group forms
      dihedral angles of 72.06 (11) and 45.44 (5) degrees  with the N-tert-but-oxy
      carbonyl group and the 2-fluoro-benzyl group, respectively. In the crystal, two
      dimensional layers of mol-ecules parallel to (001) are built through an R 4
      (4)(23) motif generated via O-H?O, C-H?O and C-H?F inter-actions, and an R 2
      (2)(11) motif generated by C-H?O and C-H?F inter-actions. 

PMID- 24109374
TI  - 3-[1-(2-Hy-droxy-anilino)ethyl-idene]-3H-chromen-2,4-dione.
AB  - The title compound is a new amino-coumarin derivative, C17H13NO4, and was
      synthesized by the condensation of 2-amino-phenol and 3-acetyl-4-hy-droxy
      coumarin. An intra-molecular N-H?O hydrogen bond generates an S(6) ring motif. In
      the crystal, the molecules are linked into chains extending in the [010]
      direction by O-H?O hydrogen bonds. There is also a pi-pi stacking inter-action
      between the bicyclic coumarin fragment and the phenol ring [centroid-centroid
      distance = 3.7510 (14) A], and these ring systems form between them a dihedral
      angle of 53.3 (2) degrees . Intermolecular hydrogen bond C-H?O hydrogen bonding
      is also observed in the interconnection of the crystal packing. 

PMID- 24109376
TI  - Thio-phene-2-carbonyl azide.
AB  - The title compound, C5H3N3OS, is almost planar (r.m.s. deviation for the ten non
      H atoms = 0.018 A) and forms an extended layer structure in the (100) plane, held
      together via hydrogen-bonding inter-actions between adjacent mol-ecules. Of
      particular note is the occurrence of RC-H?N(-)=N(+)=NR inter-actions between an
      aromatic C-H group and an azide moiety which, in conjunction with a complementary
      C-H?O=C inter-action, forms a nine-membered ring. 

PMID- 24109377
TI  - 3-(2-Bromo-phenyl-sulfin-yl)-2,5,7-trimethyl-1-benzo-furan.
AB  - In the title compound, C17H15BrO2S, both the benzo-furan and 2-bromo-phenyl rings
      are virtually planar, with r.m.s. deviations of 0.009 (2) and 0.006 (2) A,
      respectively. The dihedral angle between these mean planes is 89.31 (7) degrees .
      In the crystal, mol-ecules are linked via pairs of C-H?pi inter-actions into
      inversion dimers. These dimers are further linked by C-H?pi inter-actions into
      supra-molecular chains running along the b axis. In addition, C-S?pi inter
      actions, with an S-to-ring-centroid distance of 3.50 (2) A, are observed between
      inversion-related dimers. 

PMID- 24109378
TI  - Amitraz.
AB  - In the asymmetric unit of the title compound {systematic name: N'-(2,4-di-methyl
      phen-yl)-N-[N-(2,4-di-methyl-phen-yl)carbox-imido-yl]-N-methyl-methanimidamide},
      C19H23N3, which is a formamidine pesticide, there are two independent and
      conformationally similar mol-ecules, with the dihedral angle between the mean
      planes of the 2,4-di-methylbenzene rings in each mol-ecule being 41.63 (6) and
      42.09 (5) degrees . The crystal structure is stabilized by a C-H?N hydrogen bond,
      as well as weak inter-molecular C-H?pi and pi-pi inter-actions [ring centroid
      separation = 3.7409 (15) A], giving one-dimensional chains extending down the b
      direction. 

PMID- 24109379
TI  - N (2)-(4-Meth-oxy-salicyl-idene)arginine hemihydrate.
AB  - The title compound, C14H20N4O4.0.5H2O [systematic name: (2S)-5-{[amino-(iminium
      yl)meth-yl]amino}-2-{[(1Z)-4-meth-oxy-2-oxido-benzyl-idene]aza-nium-yl}penta
      noate hemihydrate], has been synthesized by the reaction of l-arginine and 4-meth
      oxy-salicyl-aldehyde and crystallizes with two independent substituted l-arginine
      mol-ecules and one water mol-ecule of solvation in the asymmetric unit. Each mol
      ecule exists as a zwitterion and adopts a Z configuration about the central C=N.
      The mol-ecular conformation is stabilized by strong intra-molecular N-H?O
      hydrogen bonds that generate S(6) and S(10) ring motifs. Inter-molecular N-H?O
      and O-H?O hydrogen bonds involving also the water mol-ecule and weak inter
      molecular C-H?Owater inter-actions link the mol-ecules into an infinite one
      dimensional ribbon structure extending along the b axis. The known (2S) absolute
      configuration for l-arginine was invoked. Weak intermolecular C-H?pi interactions
      are also present. 

PMID- 24109380
TI  - 4-(2-Hy-droxy-eth-oxy)phenol.
AB  - The asymmetric unit of the title compound, C8H10O3, contains four mol-ecules,
      which differ in the orientation of the hy--droxy-ethyl group [O-C-C-O torsion
      angles = -168.89 (17), 72.9 (2), -65.8 (2) and 71.8 (2) degrees ], as well as the
      orientation of the hy-droxy H atoms. Furthermore, the crystal structure displays
      two different types of strong hydrogen bond. The first is between an alcohol O-H
      and another alcohol O atom, and the second between an alcohol O-H group and an
      ether O atom. Additional weak hydrogen bonds between C-H groups and ether O atoms
      stabilize the structure. 

PMID- 24109381
TI  - 2-Hy-droxy-N'-methyl-5-nitro-benzohydrazide.
AB  - In the title compound, C8H9N3O4, there are two mol-ecules in the asymmetric unit,
      one of which is in the zwitterionic form. The zwitterion contains an intra
      molecular N-H?O hydrogen bond and the other mol-ecule contains both an intra
      molecular N-H?O and an intra-molecular O-H?O hydrogen bond. In the crystal, N-H?O
      and N-H?N hydrogen bonds link the mol-ecules, formimg a two-dimensional network
      parallel to (10-1). 

PMID- 24109382
TI  - 2-(Di-phenyl-methyl-idene)-2,3-di-hydro-1H-inden-1-one.
AB  - In the title mol-ecule, C22H16O, the indanone ring system is approximately planar
      with a dihedral angle between the fused rings of 5.13 (14) degrees . Two benzene
      rings are linked together at one side of a double bond, sitting on either side of
      the indanone ring system and making dihedral angles of 70.30 (12) and 44.74 (13)
      degrees  with it. In the crystal, hydrogen bonding is not present, but weak C
      H?pi or pi-pi inter-actions occur and mol-ecules form a sheet-like structure in
      the bc plane. 

PMID- 24109383
TI  - Absolute configuration of (1R,3S,8R,11R)-3,7,7,10-tetra-methyl-tri-cyclo
      [6.4.0.0(1,3)]dodec-9-en-11-ol.
AB  - The absolute configuration of the title compound, C16H26O, was determined as
      (1R,3S,8R,11R) based mainly on the synthetic pathway but is also implied by the X
      ray analysis. The mol-ecule contains fused six- and seven-membered rings. Part of
      the seven-membered ring was refined as disordered over two sets of sites with the
      occupancy ratio fixed at 0.86:0.14. The disorder corresponds to a major chair
      conformation and a minor boat conforation. In the crysyal, O-H?O hydrogen bonds
      connect the mol-ecules into chains parallel to the a axis. 

PMID- 24109384
TI  - Methyl 2-(2,2-dimethyl-3a,6a-di-hydro-furo[3,2-d][1,3]dioxol-5-yl)-4-oxo-4H
      chromene-3-carboxyl-ate.
AB  - In the title mol-ecule, C18H16O7, the dioxolane ring adopts an envelope
      conformation with the dimethyl-substituted C atom as the flap. The furan ring is
      almost coplanar with the pyran ring, with a dihedral angle of 1.04 (10) degrees 
      between the planes, and it makes a dihedral angle of 67.97 (11) degrees  with the
      mean plane of the dioxolane ring. The latter makes a dihedral angle of 67.15 (10)
      degrees  with the pyran ring. The O atom attached to the pyran ring deviates by 
      0.009 (1) A. The crystal packing features C-H?O hydrogen bonds, forming a three
      dimensional structure. The meth-oxy-carbonyl atoms are disordered over two
      positions, with a refined occupancy ratio of 0.508 (18):0.492 (18). 

PMID- 24109385
TI  - 2-(Benz-yloxy)iso-quinoline-1,3(2H,4H)-dione.
AB  - The title compound, C16H13NO3, exists in the keto form and the iso-quinoline
      system is essentially planar (mean deviation = 0.0424 A). The dihedral angle
      between the aromatic rings is 4.2 (2) degrees . In the crystal, mol-ecules are
      linked via weak C-H?O hydrogen bonds and C-H?pi inter-actions, forming a three
      dimensional structure. 

PMID- 24109386
TI  - 2-Hy-droxy-iso-quinoline-1,3(2H,4H)-dione.
AB  - The title mol-ecule, C9H7NO3, exists in the diketo form and the iso-quinoline
      unit is approximately planar (r.m.s. deviation = 0.0158 A). In the crystal, mol
      ecules are linked into inversion dimers through pairs of O-H?O hydrogen bonds and
      are further assembled into the (100) layers via stacking inter-actions [centroid
      centroid distances = 3.460 (3) and 3.635 (4) A]. 

PMID- 24109387
TI  - 2-(4-Oxo-3-phenyl-1,3-thia-zolidin-2-yl-idene)propanedi-nitrile.
AB  - In the title compound, C12H7N3OS, the five-membered 1,3-thia-zolidine ring is
      nearly planar [maximum deviation = 0.032 (2) A] and makes a dihedral angle of
      84.14 (9) degrees  with the phenyl ring. In the crystal, mol-ecules are linked by
      C-H?N hydrogen bonds into infinite chains along [-101]. C-H?pi inter-actions
      contribute to the arrangement of the mol-ecules into layers parallel to (101). 

PMID- 24109388
TI  - 1,10,10-Trimethyl-5-phenyl-3-oxa-4-aza-tri-cyclo-[5.2.1.0(2,6)]dec-4-en-2-ol.
AB  - The title compound, C17H21NO2, was synthesized by the reaction of (1R)-(+)-3
      benzyl-camphor and hydroxyl-amine. The oxazole ring makes a dihedral angle of
      23.42 (16) degrees  with the phenyl ring. The six-membered ring of the norboryl
      group adopts a boat conformation, whereas each of the five-membered rings of the
      norboryl group displays a flattened envelope conformation, with the C atom
      carrying the methyl groups representing the flap for both rings. In the crystal,
      mol-ecules are linked into zigzag chains propagating along the b axis by O-H?N
      hydrogen bonds. 

PMID- 24109389
TI  - 2-[1-(2-Hy-droxy-4-meth-oxy-phen-yl)ethyl-idene]-N-methyl-hydrazinecarbo-thio
      amide.
AB  - In the title compound, C11H15N3O2S, the dihedral angle between the mean planes of
      the benzene ring and hydrazinecarbo-thio-amide group is 9.2 (1) degrees . An
      intra-molecular O-H?N hydrogen bond is observed, serving to maintain an
      approximately planar conformation for the molecule. In the crystal, inversion
      dimers linked by C-H?O inter-actions occur. Further C-H?O contacts link dimers
      into (010) chains. 

PMID- 24109390
TI  - N,N-Diethyl-4-[1-phenyl-3-(pyridin-2-yl)-4,5-di-hydro-1H-pyrazol-5-yl]aniline.
AB  - In the title mol-ecule, C24H26N4, the pyrazoline ring assumes an envelope
      conformation with the aniline-bearing C atom at the flap position. The benzene
      ring and the pyridine ring form with the pyrazoline ring dihedral angles of 4.53
      (1) and 6.26 (1) degrees , respectively. In turn, the aniline group is nearly
      perpendicular to the pyrazoline ring [dihedral angle = 79.96 (1) degrees ]. The
      ethyl groups of the di-ethyl-amine substituent are disordered over two sets of
      sites, with an occupancy ratio of 0.624 (8):0.376 (8). 

PMID- 24109391
TI  - 2-Chloro-3-[(2-oxo-2H-chromen-6-yl)amino]-naphthalene-1,4-dione.
AB  - In the title compound, C19H10ClNO4, the dihedral angle between the naphtho
      quinone and coumarin rings is 48.99 (6) degrees . In the crystal, mol-ecules are
      linked by strong N-H?O hydrogen bonds into chains with graph-set motif C(6) along
      [101]. The packing also features pi-pi stacking inter-actions between naphtho
      quinone and coumarin rings [centroid-to-centroid distances = 3.7679 (12) and
      3.6180 (13) A]. 

PMID- 24109392
TI  - (2E)-3-(2-Chloro-8-methyl-quinolin-3-yl)-1-(2-methyl-4-phenyl-quinolin-3-yl)prop
      2-en-1-one.
AB  - In the title compound, C29H21ClN2O, there is a twist in the bridging prop-2-en-1
      one group [C=C-C=O torsion angle = 22.7 (2) degrees ]. The quinolinyl residues
      form a dihedral angle of 86.92 (4) degrees , indicating an almost perpendicular
      relationship. In the crystal, supra-molecular layers in the bc plane are
      stabilized by C-H?pi and pi-pi inter-actions [centroid-centroid distance = 3.4947
      (7) A]. 

PMID- 24109393
TI  - (2E)-3-(6-Chloro-2-meth-oxy-quinolin-3-yl)-1-(2-methyl-4-phenyl-quinolin-3
      yl)prop-2-en-1-one acetone monosolvate.
AB  - In the title solvate, C29H21ClN2O2.C3H6O, a prop-2-en-1-one bridge links two
      quinolinyl residues; the latter are almost perpendicular [dihedral angle = 78.27
      (6) degrees ]. The dihedral angle between the quinonyl ring system and its
      pendant phenyl group is 59.78 (8) degrees . A small twist in the bridging prop-2
      en-1-one group is noted [O=C-C=C torsion angle = -10.6 (3) degrees ]. In the
      crystal, a three-dimensional architecture arises as a result of C-H?O and pi-pi
      stacking [centroid-centroid distances = 3.5504 (12)-3.6623 (12) A]. 

PMID- 24109394
TI  - N'-Phenyl-N'-[3-(2,4,5-triphenyl-2,5-di-hydro-1H-pyrazol-3-yl)quinoxalin-2
      yl]benzohydrazide.
AB  - The mol-ecule of the title compound, C42H32N6O, is built up from one pyrazole
      ring linked to three phenyl rings and to an approximately planar [maximum
      deviation = 0.0455 (15) A] quinoxaline system connected to a phenyl
      benzohydrazide group. The pyrazole ring assumes an envelope conformation, the C
      atom attached to the quinoxalin-3-yl ring system being the flap atom. The
      dihedral angle between the two phenyl rings of the phenyl-benzohydrazide group is
      of 58.27 (9) degrees . The mean plane through the pyrazole ring is nearly
      perpendicular to the quinoxaline ring system and to the phenyl ring attached to
      the opposite side, forming dihedral angles of 82.58 (7) and 87.29 (9) degrees ,
      respectively. An intra-molecular C-H?O hydrogen bond is present. In the crystal,
      mol-ecules are linked by pairs of N-H?N hydrogen bonds, forming inversion dimers,
      which are further connected by C-H?N hydrogen bonds into chains parallel to the b
      axis. 

PMID- 24109395
TI  - 1-[(E)-2-(2-Hy-droxy-5-methyl-phen-yl)diazen-2-ium-1-yl]naphthalen-2-olate.
AB  - The title zwitterion, C17H14N2O2, crystallizes with two independent mol-ecules in
      the asymmetric unit, both of which are approximately planar, the dihedral angles
      between the benzene ring and the naphthalene ring system being 4.39 (12) degrees 
      in one mol-ecule and 5.83 (12) degrees  in the other, and show an E conformation
      with respect to the azo double bond. An intra-molecular N-H?O hydrogen bond in
      each molecule helps to establish their near planar conformation. In the crystal,
      mol-ecules are linked through O-H?O hydrogen bonds into infinite chains running
      along the a-axis direction. In addition, the chains are stacked along the b axis
      via pi-pi inter-actions between the benzene and the naphthalene rings of adjacent
      mol-ecules, the centroid-centroid distances being 3.722 (3) and 3.823 (4) A. 

PMID- 24109396
TI  - (1Z,2E)-1-(3,4-Diphenyl-2,3-di-hydro-1,3-thia-zol-2-yl-idene)-2-(1-p-tolyl-ethyl
      idene)hydrazine.
AB  - In the title compound, C24H21N3S, the thia-zole ring makes dihedral angles of
      52.03 (6), 62.63 (6) and 12.35 (6) degrees , respectively, with the two phenyl
      rings and the benzene ring. In the crystal, weak C-H?pi inter-actions occur
      between inversion-related mol-ecules. 

PMID- 24109397
TI  - 1,3-Bis[(5-amino-furan-2-yl)meth-yl]-3,4,5,6-tetra-hydro-pyrimidin-1-ium hexa
      fluoro-phosphate.
AB  - The asymmetric unit of the title salt, C16H21N2O2 (+).PF6 (-), contains half of
      the whole ion pair, which has crystallographic mirror symmetry. Two F atoms
      related by the mirror plane are disordered over two sites of equal occupancy. The
      dihedral angle between the central ring and the furan ring is 59.3 () degrees .
      In the crystal, the anions and cations are linked through C-H?F inter-actions,
      forming a three-dimensional network. 

PMID- 24109398
TI  - 2-[4-(2-Chloro-acet-yl)phen-yl]-2-methyl-1-(pyrrolidin-1-yl)propan-1-one.
AB  - The asymmetric unit of the title compound, C16H20ClNO2, contains two mol-ecules
      in which the dihedral angles between the benzene ring and the plane of the amide
      unit are 77.4 (1) and 81.1 (1) degrees . In both mol-ecules, the five-membered
      ring adopts an envelope conformation with one of the beta-C atoms as the flap. In
      the crystal, mol-ecules are connected via C-H?O hydrogen bonds, forming chains
      along the b-axis direction. These chains are further linked by C-H?pi inter
      actions, forming a three-dimensional network. 

PMID- 24109399
TI  - 1-Benzoyl-4-thio-biuret.
AB  - IN THE TITLE COMPOUND (SYSTEMATIC NAME: {[(phenyl-formamido)-carbon-yl]amino}
      methane-thio-amide), C9H9N3O2S, both benzoyl and terminal thio-urea fragments
      adopt transoid conformations with respect to the central carbonyl O atom. The
      benzoyl and thio-biuret groups are almost coplanar, making a dihedral angle of
      4.40 (8) degrees . The mol-ecular structure is stabilized by two intra-molecular
      N-H?O hydrogen bonds. In the crystal, N-H?O and N-H?S hydrogen bonds link the mol
      ecules into a tape running along [101].

PMID- 24109400
TI  - 1-Ethyl-4'-(1H-indol-3-ylcarbon-yl)-1'-methyl-2,2''-dioxodi-spiro-[indoline-3,2'
      pyrrolidine-3',3''-indoline]-4'-carbo-nitrile dimethyl sulfoxide monosolvate.
AB  - In the title compound, C31H25N5O3.C2H6OS, the three indole/indoline units are all
      essentially planar with maximum deviations of 0.0172 (3), 0.053 (2) and 0.07 (2)
      A. The pyrrolidine ring adopts an envelope conformation with the C atoms bearing
      the 1-ethyl-2-oxo-indole substituent (in which the five-membered ring adopts a
      twisted conformation) as the flap. The dimethyl sulfoxide solvent mol-ecule is
      disordered over two positions, with an occupancy factor ratio of 0.871 (4):0.129
      (4). The solvent components are linked to the heterocyclic mol-ecule via C-H?O
      and C-H?S hydrogen bonds. In the crystal, the solvent components are linked to
      the heterocyclic molecule via C-H?O and C-H?S inter-actions, forming R 2 (2)(10)
      ring motifs. The mol-ecules are further connected into a chain along the a-axis
      direction via N-H?O hydrogen bonds. 

PMID- 24109401
TI  - 1-(2,6-Diiso-propyl-phen-yl)-1H-benzimidazole.
AB  - In the title compound, C19H22N2, both the benzimidazole unit and the 2,6-diiso
      propyl-phenyl group are essentially planar [maximum deviations from the least
      squares planes of 0.005 (1) and 0.009 (1) A, respectively]. The dihedral angle
      between the two planes is 79.6 (7) degrees . In the crystal, mol-ecules are
      linked into chains along the a-axis direction by weak C-H?N inter-actions. The
      crystal structure also features C-H?pi inter-actions, which link the chains into
      a three-dimensional network. 

PMID- 24109402
TI  - N'-(4-Ethyl-cyclo-hexyl-idene)-5-fluoro-3-phenyl-1H-indole-2-carbohydrazide.
AB  - The title compound, C23H24FN3O, crystallizes with two independent mol-ecules (I
      and II) in the asymmetric unit. These pairs of mol-ecules are linked to each
      other as N-H?O dimers with an R 2 (2)(10) motif. Furthermore, the crystal
      structure also exhibits C-H?pi inter-actions. The atoms of the ethyl group in mol
      ecule I are disordered over two sites with an occupancy ratio of 0.817 (6):0.183
      (6). 

PMID- 24109403
TI  - 1-[6-(3,5-Di-methyl-pyrazol-1-yl)-1,2,4,5-tetra-zin-3-yl]guanidin-2-ium
      perchlorate methanol monosolvate.
AB  - In the title solvated salt, C8H12N9 (+).ClO4 (-).CH3OH, the dihedral angle
      between the tetra-zine and pyrazole rings is 26.05 (7) degrees . The two N atoms
      bonded to the 1,2,4,5-tetra-zine ring deviate from the plane defined by its four
      N atoms by 0.234 (2) and 0.186 (2) A. There is an intra-molecular N-H?N hydrogen
      bond between the protonated guanidine fragment and one of the tetra-zine N atoms.
      In the crystal, two cations and two perchlorate anions are connected via N-H?O
      hydrogen bonds into centrosymmetric assemblies. These assemblies are further
      linked into a two-dimensional network parallel to (100) via bifurcated O-H?(N,N)
      hydrogen bonds formed with the bridging methanol mol-ecules. 

PMID- 24109404
TI  - A triclinic polymorph of (E)-2-(4-iso-butyl-phen-yl)-N'-[1-(4-nitro-phen-yl)ethyl
      idene]propano-hydrazide.
AB  - The asymmetric unit of the triclinic polymorph of the title compound, C21H25N3O3,
      consists of two mol-ecules, whereas for the monoclinic polymorph Z' = 1 [Fun et
      al. (2009 ?). Acta Cryst. E65, o445]. The two mol-ecules exhibit an E
      configuration with respect to the C=N bond. The mol-ecules are linked into dimers
      by N-H?O and C-H?O hydrogen bonds forming R 2 (2)(8) ring motifs. In addition, pi
      pi inter-actions occur between nitro-phenyl groups [minimum centroid-centroid
      distance 3.940 (2) A], stacking the molecules along the ac plane. 

PMID- 24109405
TI  - 5-[1-(1,3-Dimethyl-2,4,6-trioxohexa-hydropyrimidin-5-yl)-2-oxoprop-yl]-1,3-di
      methyl-pyrimidine-2,4,6(1H,3H,5H)-trione.
AB  - The title compound, C15H18N4O7, is a product of the substitution reaction of 5,5
      di-bromo-1,3-di-methyl-barbituric acid with sodium sulfide in aqueous acetone. In
      the crystal, mol-ecules display neither inter-molecular nor intra-molecular
      hydrogen bonding and the two barbiturate rings adopt the keto form. 

PMID- 24109406
TI  - (E)-1-(2-Phenyl-diazen-2-ium-1-yl)naph-thalen-2-olate.
AB  - In the title zwitterionic compound, C16H12N2O, the dihedral angle between the
      phenyl ring and the naphthalene ring system is 17.85 (8) degrees ; an intra
      molecular N-H?O hydrogen bond occurs. In the crystal, pi-pi stacking is observed
      between naphthalene ring systems of adjacent mol-ecules, the centroid-centroid
      distance being 3.6486 (11) A. 

PMID- 24109407
TI  - 1-(5-Bromo-2-oxoindolin-3-yl-idene)-4-phenyl-thio-semicarbazide.
AB  - In the title compound, C15H11BrN4OS, the least-squares plane through the 5-bromo
      isatin fragment forms a dihedral angle of 13.63 (14) degrees  with the phenyl
      ring. The mol-ecular conformation features intra-molecular N-H?N and N-H?O
      hydrogen bonds. In the crystal, mol-ecules are connected via pairs of N-H?O inter
      actions into centrosymmetric dimers. Additionally, pi-pi stacking inter-actions
      link mol-ecules into chains parallel to the a axis with short C?C distances being
      observed between the phenyl and thio-carbonyl [3.236 (8) A] groups and between
      the thio-carbonyl and carbonyl [3.351 (4) A] groups of stacked mol-ecules. 

PMID- 24109408
TI  - 3-Amino-4-(1,3-benzoxazol-2-yl)-5-(cyclo-hexyl-amino)-thio-phene-2-carbo-nitrile.
AB  - In the title compound, C18H18N4OS, the cyclo-hexyl ring adopts a chair
      conformation. The other rings of this compound lie almost in the same plane, with
      a mean deviation of 0.03 (2) A from the least-squares plane defined by the 14
      constituent atoms. There are intra-molecular N-H?N and N-H?O hydrogen bonds, as
      well as inter-molecular N-H?N hydrogen bonds, which link the mol-ecules into
      centrosymmetric dimers. 

PMID- 24109409
TI  - 2-Hy-droxy-methyl-1,3-dimethyl-1H-imidazol-3-ium triiodide.
AB  - The crystal packing of the title salt, C6H11N2O(+).I3 (-), can be described as
      consisting of alternating layers of cations and anions parallel to the (100)
      plane along the a-axis direction. The components are linked by O-H?I, C-H?I and C
      H?O interactions, generating a three-dimensional network. The O atom deviates
      from the imidazol ring by 0.896 (2) A. 

PMID- 24109410
TI  - N'-{(E)-[5-(Hy-droxy-meth-yl)furan-2-yl]methyl-idene}pyridine-4-carbohydrazide
      dihydrate.
AB  - In the title compound, C12H11N3O3.2H2O, the dihedral angle formed by the planes
      of the pyridine and the furan rings of the organic carbohydrazide mol-ecule is
      4.66 (7) degrees . In the crystal, these mol-ecules form stacks along the b-axis
      direction, neighbouring mol-ecules within each stack being related by inversion
      and the shortest distance between the centroids of the pyridine and furan rings
      being 3.714 (1) A. Mol-ecules from neighboring stacks are linked by pairs of N
      H?O hydrogen bonds. The water mol-ecules fill the channels between the stacks
      being linked by O-H?O hydrogen bonds into helices along [010]. Besides this,
      water mol-ecules are involved in O-H?N and O-H?O hydrogen bonds with the
      carbohydrazide mol-ecules, thus forming a three-dimensional network, augmented by
      weak C-H?O interactions. 

PMID- 24109411
TI  - Flunarizinium hydrogen maleate.
AB  - In the cation of the title salt {systematic name: 4-[bis-(4-fluoro-phen-yl)meth
      yl]-1-[(2E)-3-phenyl-prop-2-en-1-yl]piperazin-1-ium hydrogen maleate}, C26H27F2N2
      (+).C4H3O4 (-), the protonated piperazine ring is in a chair conformation. The
      dihedral angle between the 4-fluoro-phenyl rings is 68.2 (2) degrees . An intra
      molecular O-H?O hydrogen bond occurs in the anion. In the crystal, N-H?O, C-H?O
      and C-H?F inter-actions are observed, which link the ions into [001] chains. 

PMID- 24109412
TI  - 1''-Allyl-5''-(4-meth-oxy-benzyl-idene)-7'-(4-methoxy-phen-yl)-1',3',5',6',7',7a'
      hexa-hydro-dispiro-[ace-naphthyl-ene-1,5'-pyrrolo-[1,2-c][1,3]thia-zole-6',3''
      piperidine]-2,4''(1H)-dione.
AB  - In the title compound, C39H36N2O4S, the piperidine ring adopts a twisted half
      chair conformation. In the pyrrolo-thia-zole fused-ring system, the pyrrole ring
      adopts an envelope conformation (with the C atom bound to the thia-zole ring
      being the flap atom) and the thia-zole ring also exhibits an envelope
      conformation (with the N atom bound to the pyrrole ring as the flap). The mol
      ecular structure features a weak intra-molecular C-H?O inter-action. In the
      crystal, a C-H?O inter-action forms a linear chain along the diagonal of the ac
      plane, generating a C(14) graph-set motif. A weak C-H?pi inter-action also
      occurs. 

PMID- 24109413
TI  - (E)-2,2'-[3-(4-Chloro-phen-yl)prop-2-ene-1,1-di-yl]bis-(3-hy-droxy-5,5-di-methyl
      cyclo-hex-2-en-1-one).
AB  - The title compound, C25H29ClO4, adopts a trans conformation about the C=C double
      bond and the di-methyl-cyclo-hexenone rings both show an envelope conformation
      with the dimethyl-substituted C atom as the flap. In the mol-ecule, the hy-droxy
      and carbonyl groups form two intra-molecular O-H?O hydrogen bonds typical for
      xanthene derivatives. In the crystal, weak C-H?O hydrogen bonds link the mol
      ecules into chains running parallel to the a-axis direction. 

PMID- 24109414
TI  - 1-Di-chloro-acetyl-t-3-isopropyl-r-2,c-6-di-phenyl-piperidin-4-one.
AB  - In the title compound, C22H23Cl2NO2, the piperidine ring adopts a twist-boat
      conformation. The phenyl rings substituted at the 2- and 6-positions of the
      piperidine ring subtend dihedral angles of 60.6 (2) and 84.2 (1) degrees ,
      respectively, with the mean plane of the piperidine ring. In the crystal, mol
      ecules are linked by C-H?O inter-actions into zigzag chains running along the c
      axis direction. 

PMID- 24109415
TI  - 2-[(E)-(5-Chloro-2-methyl-phen-yl)imino-meth-yl]-4-methyl-phenol.
AB  - In the mol-ecule of the title Schiff base compound, C15H14ClNO, the two benzene
      rings are twisted with respect to each other, with a dihedral angle of 35.0 (3)
      degrees ; an intra-molecular O-H?N hydrogen bond occurs. In the crystal, weak C
      H?pi inter-actions between methyl groups and chloro-phenyl rings link the mol
      ecules into supra-molecular chains running along the a axis. 

PMID- 24109416
TI  - (1S,3S,8R,10R,11R)-3,7,7,10-Tetra-methyl-tri-cyclo-[6.4.0.0(1,3)]dodecan-11-ol.
AB  - The title compound, C16H28O, was synthesized by three steps from beta-himachalene
      (3,5,5,9-tetra-methyl-2,4a,5,6,7,8-hexa-hydro-1H-benzo-cyclo-heptene), which was
      isolated from the essential oil of the Atlas cedar (Cedrus atlantica). The mol
      ecule is built up from fused six- and seven-membered rings and an appended three
      membered ring. The six-membered ring has twist-boat conformation, whereas the
      seven-membered ring displays a chair conformation. In the crystal, mol-ecules are
      linked into chains propagating along the a-axis direction by O-H?O hydrogen
      bonds. 

PMID- 24109417
TI  - Bruceolline J: 2-hy-droxy-3,3-dimethyl-2,3-di-hydro-cyclo-penta-[b]indol-1(4H)
      one.
AB  - The 12-membered cyclo-penta-[b]indole ring system in the title compound,
      C13H13NO2, deviates only slightly from planarity (r.m.s. deviation = 0.051 A). In
      the crystal, N-H?O and O-H?O hydrogen bonds link the mol-ecules into sheets
      parallel to (100). The five-membered cyclopentanone ring is in slightly distorted
      envelope conformation with the C atom bearing the hydroxy substituent as the
      flap. 

PMID- 24109418
TI  - N-(2-Allyl-4-chloro-2H-indazol-5-yl)-4-meth-oxy-benzene-sulfonamide hemi-hydrate.
AB  - The fused five- and six-membered rings in the title compound,
      C17H16ClN3O3S.0.5H2O, are practically coplanar, with the maximum deviation from
      the mean plane being 0.057 (3) A for the C atom bound to the exocyclic N atom.
      The indazole system makes a dihedral angle of 66.18 (12) degrees  with the plane
      through the benzene ring, and it is nearly perpendicular to the allyl group, as
      indicated by the N-N-C-C torsion angle of 79.2 (3) degrees . In the crystal, the
      water mol-ecule, lying on a twofold axis, forms O-H?N and accepts N-H?O hydrogen
      bonds. Additional C-H?O hydrogen bonds contribute to the formation of a chain
      along the b-axis direction. 

PMID- 24109419
TI  - (E)-2-[(2-Formyl-phen-oxy)meth-yl]-3-(4-iso-propyl-phen-yl)acrylo-nitrile.
AB  - In the title compound, C20H19NO2, the dihedral angle between the benzene rings is
      77.12 (8) degrees . The terminal isopropyl group is disordered over two
      orientations, with site occupancies of 0.720 (14) and 0.280 (14). In the crystal,
      mol-ecules are linked through a weak C-H?O inter-action, forming a zigzag chain
      along the c-axis direction. 

PMID- 24109420
TI  - 4-[4-(Hept-yloxy)benzo-yloxy]phenyl 2-oxo-7-tri-fluoro-methyl-2H-chromene-3
      carboxyl-ate.
AB  - The title compound, C31H27F3O7, is a liquid crystal and exhibits enanti-otropic
      SmA and nematic phase transitions. In the crystal, the the 2H-chromene ring
      system makes dihedral angles of 54.46 (17) and 7.79 (16) degrees , respectively,
      with the central benzene ring and 4-(hept-yloxy)benzene ring. The three F atoms
      of the -CF3 group are disordered over two sets of sites, with an occupancy ratio
      of 0.62 (3):0.38 (3). The crystal structre features two pairs of C-H?O hydrogen
      bonds, which form inversion dimers and generate R 2 (2)(10) and R 2 (2)(30) ring
      patterns. C-H?O inter-actions along [100] and C-H?pi inter-actions futher
      consolidate the packing, leading to a three-dimensional network. 

PMID- 24109421
TI  - Quinoline-2-sulfonamide.
AB  - In the title compound, C9H8N2O2S, the sulfamoyl -NH2 group is involved in inter
      molecular hydrogen bonding with the sulfonamide O and quinoline N atoms. In the
      crystal, mol-ecules are linked into dimers via pairs of N-H?N hydrogen bonds,
      forming an R 2 (2)(10) motif. The dimers are further assembled into chains
      parallel to the b axis through N-H?O hydrogen bonds, generating a C(4) motif. The
      crystal packing is additionally stabilized by inter-molecular C-H?O inter
      actions. The crystal studied was a non-merohedral twin with a domain ratio of
      0.938 (2):0.062 (2). Density functional theory (DFT) calculations, at the B3LYP/6
      31 G(d,p) level of theory, were used to optimize the mol-ecular structure and to
      determine inter-action energies for the title compound. The resulting inter
      action energy is ~4.4 kcal mol(-1) per bridge for the C(4) chain and ~5.9 kcal
      mol(-1) per bridge for the R 2 (2)(10) motif. 

PMID- 24109422
TI  - Bis(1-ethyl-3-methyl-imidazolium) 3,6-diselanyl-idene-1,2,4,5-tetra-selena-3,6
      diphospha-cyclo-hexane-3,6-di-selen-olate.
AB  - In the title compound, 2C6H11N2 (+).P2Se8 (2-) or [EMIM]2P2Se8 (EMIM = 1-ethyl-3
      methyl-imidazolium), the anions, located about inversion centers between EMIM
      cations, exhibit a cyclo-hexane-like chair conformation. The cations are found in
      columns along the a axis, with centroid-centroid distances of 3.8399 (3) and
      4.7530 (2) A. The observed P-Se distances and Se-P-Se angles agree with other
      salts of this anion. 

PMID- 24109423
TI  - 2,4-Di-bromo-1,3-dihy-droxy-9H-xanthen-9-one.
AB  - The title compound, C13H6Br2O4, derived from xanthone, a fundamental structural
      framework of active ingredients in many medicinal plants, and was synthesized by
      bromination of 1,3-di-hydroxyxanthen-9-one with N-bromo-succinimide. The mol
      ecular conformation is essentially planar, the dihedral angle between the benzene
      rings being 1.1 (4) degrees . This conformation is favorable for the formation of
      an intra-molecular O-H?O hydrogen bond between a hy-droxy group and the xanthone
      carbonyl group. In the crystal, mol-ecules are associated into chains along the b
      axis direction via C=O?H-O hydrogen bonds involving the other hy-droxy group. 

PMID- 24109424
TI  - Tris(4-formyl-phen-yl)phosphane oxide tetra-hydro-furan hemisolvate.
AB  - The title compound, C21H15O4P.0.5C4H8O, contains an ordered phosphane oxide in a
      general position and a tetra-hydro-furan solvent mol-ecule disordered about a
      twofold axis. All three aldehyde substituents are nearly coplanar with their
      attached benzene rings, with C-C-C-O torsion angles in the range 1.64 (17)-4.24
      (19) degrees . All three have different conformations with respect to the P=O
      group, one syn, one anti, and one gauche. Two of the aldehyde substituents form
      inter-molecular C-H?O contacts. 

PMID- 24109425
TI  - 2-Di-phenyl-phosphanyl-1-methyl-1H-benzimidazole.
AB  - In the title compound, C20H18N2P, the P atom is bonded to the two phenyl and
      imidazole groups, with an average P-C bond length of 1.828 (2) A. The three C-P-C
      bond angles have values consistent with a tetra-hedral geometry around the P atom
      with the fourth site occupied by a H atom. Crystal packing is through van der
      Waals inter-actions. 

PMID- 24109428
TI  - Cerebrospinal fluid: a rising subject in brain development.

PMID- 24109427
TI  - Imaging stretch-activated firing of spinal afferent nerve endings in mouse colon.
AB  - Spinal afferent neurons play a major role in detecting noxious and innocuous
      stimuli from visceral organs, such as the gastrointestinal tract. However, all
      our understanding about spinal afferents has been obtained from recordings of
      spinal afferent axons, or cell bodies that lie outside the gut wall, or
      peripheral organ they innervate. No recordings have been made directly from
      spinal afferent nerve endings, which is where sensory transduction occurs. We
      developed a preparation whereby recordings could be made from rectal afferent
      nerve endings in the colon, to characterize mechanisms underlying sensory
      transduction. Dorsal root ganglia (L6-S2) were removed from mice, whilst
      retaining neural continuity with the colon. Fluo-4-AM was used to record from
      rectal afferent nerve endings in myenteric ganglia and circular muscle at 36
      degrees C. In slack (unstretched) preparations of colon, no calcium transients
      were recorded from spinal afferent endings. However, in response to a maintained
      increase in circumferential diameter, a maintained discharge of calcium
      transients occurred simultaneously in multiple discrete varicosities along single
      axons of rectal afferents in myenteric ganglia and circular muscle. Stretch
      activated calcium transients were resistant to hexamethonium and nifedipine, but
      were abolished by tetrodotoxin, CPA, BAPTA-AM, cobalt, gadolinium, or replacement
      of extracellular Na(+) with NMDG. In summary, we present a novel preparation in
      which stretch-activated firing of spinal afferent nerve endings can be recorded,
      using calcium imaging. We show that circumferential stretch of the colon
      activates a maintained discharge of calcium transients simultaneously in
      varicosities along single rectal afferent endings in myenteric ganglia and
      circular muscle. Non-selective cation channels, TTX-sensitive Na(+) channels and
      both extracellular calcium influx and intracellular Ca(2+) stores are required
      for stretch-activated calcium transients in rectal afferent endings. 

PMID- 24109426
TI  - Metabolic disturbances connecting obesity and depression.
AB  - Obesity markedly increases the odds of developing depression. Depressed mood not
      only impairs motivation, quality of life and overall functioning but also
      increases the risks of obesity complications. Abdominal obesity is a better
      predictor of depression and anxiety risk than overall adipose mass. A growing
      amount of research suggests that metabolic abnormalities stemming from central
      obesity that lead to metabolic disease may also be responsible for the increased
      incidence of depression in obesity. As reviewed here, a higher mass of
      dysfunctional adipose tissue is associated with several metabolic disturbances
      that are either directly or indirectly implicated in the control of emotions and
      mood. To better comprehend the development of depression in obesity, this review
      pulls together select findings addressing the link between adiposity, diet and
      negative emotional states and discusses the evidence that alterations in
      glucocorticoids, adipose-derived hormones, insulin and inflammatory signaling
      that are characteristic of central obesity may be involved. 

PMID- 24109429
TI  - Contribution of PGE2 EP1 receptor in hemin-induced neurotoxicity.
AB  - Although hemin-mediated neurotoxicity has been linked to the production of free
      radicals and glutamate excitotoxicity, the role of the prostaglandin E2 (PGE2)
      EP1 receptor remains unclear. Activation of the EP1 receptor in neurons results
      in increased intracellular calcium levels; therefore, we hypothesize that the
      blockade of the EP1 receptor reduces hemin neurotoxicity. Using postnatal primary
      cortical neurons cultured from wild-type (WT) and EP1(-/-) mice, we investigated
      the EP1 receptor role in hemin neurotoxicity measured by lactate dehydrogenase
      (LDH) cell survival assay. Hemin (75 MUM) induced greater release of LDH in WT
      (34.7 +/- 4.5%) than in EP1(-/-) (27.6 +/- 3.3%) neurons. In the presence of the
      EP1 receptor antagonist SC-51089, the hemin-induced release of LDH decreased. To
      further investigate potential mechanisms of action, we measured changes in the
      intracellular calcium level [Ca(2+)]i following treatment with 17-phenyl trinor
      PGE2 (17-pt-PGE2) a selective EP1 agonist. In the WT neurons, 17-pt-PGE2 dose
      dependently increased [Ca(2+)]i. However, in EP1(-/-) neurons, [Ca(2+)]i was
      significantly attenuated. We also revealed that hemin dose-dependently increased
      [Ca(2+)]i in WT neurons, with a significant decrease in EP1(-/-) neurons. Both 17
      pt-PGE2 and hemin-induced [Ca(2+)]i were abolished by N-methyl-D-aspartic (NMDA)
      acid receptor and ryanodine receptor blockers. These results suggest that
      blockade of the EP1 receptor may be protective against hemin neurotoxicity in
      vitro. We speculate that the mechanism of hemin neuronal death involves [Ca(2+)]i
      mediated by NMDA acid receptor-mediated extracellular Ca(2+) influx and EP1
      receptor-mediated intracellular release from ryanodine receptor-operated Ca(2+)
      stores. Therefore, blockade of the EP1 receptor could be used to minimize
      neuronal damage following exposure to supraphysiological levels of hemin. 

PMID- 24109430
TI  - Lack of serotonin reuptake during brain development alters rostral raphe
      prefrontal network formation.
AB  - Besides its "classical" neurotransmitter function, serotonin (5-HT) has been
      found to also act as a neurodevelopmental signal. During development, the 5-HT
      projection system, besides an external placental source, represents one of the
      earliest neurotransmitter systems to innervate the brain. One of the targets of
      the 5-HT projection system, originating in the brainstem raphe nuclei, is the
      medial prefrontal cortex (mPFC), an area involved in higher cognitive functions
      and important in the etiology of many neurodevelopmental disorders. Little is
      known, however, about the exact role of 5-HT and its signaling molecules in the
      formation of the raphe-prefrontal network. Using explant essays, we here studied
      the role of the 5-HT transporter (5-HTT), an important modulator of the 5-HT
      signal, in rostral raphe-prefrontal network formation. We found that the
      chemotrophic nature of the interaction between the origin (rostral raphe cluster)
      and a target (mPFC) of the 5-HT projection system was affected in rats lacking
      the 5-HTT (5-HTT(-/-)). While 5-HTT deficiency did not affect the dorsal raphe 5
      HT-positive outgrowing neurites, the median raphe 5-HT neurites switched from a
      strong repulsive to an attractive interaction when co-cultured with the mPFC.
      Furthermore, the fasciculation of the mPFC outgrowing neurites was dependent on
      the amount of 5-HTT. In the mPFC of 5-HTT(-/-) pups, we observed clear
      differences in 5-HT innervation and the identity of a class of projection neurons
      of the mPFC. In the absence of the 5-HTT, the 5-HT innervation in all subareas of
      the early postnatal mPFC increased dramatically and the number of Satb2-positive
      callosal projection neurons was decreased. Together, these results suggest a 5
      HTT dependency during early development of these brain areas and in the formation
      of the raphe-prefrontal network. The tremendous complexity of the 5-HT projection
      system and its role in several neurodevelopmental disorders highlights the need
      for further research in this largely unexplored area. 

PMID- 24109431
TI  - Increased physical activity is not enough to recover astrocytic population from
      dark-rearing. Synergy with multisensory enrichment is required.
AB  - Elimination of sensory inputs (deprivation) modifies the properties of the
      sensory cortex and serves as a model for studying plasticity during postnatal
      development. Many studies on the effects of deprivation have been performed in
      the visual cortex using dark-rearing as a visual deprivation model. It induces
      changes in all cellular and molecular components, including astrocytes, which
      play an important role in the development, maintenance, and plasticity of the
      cortex, mediated by cytokines which have been termed angioglioneurins. When one
      sense is deprived, a compensatory mechanism called cross-modal plasticity
      increases performance in the remaining senses. Environmental enrichment is so far
      the best-known method to compensate sensorial deprivation. The aim of this work
      is to study the effects of exercise alone, and of an enriched environment
      combined with exercise, on astroglial population in order to observe the effects
      of exercise by itself, or the potential synergistic effect during the rat visual
      system development. Pregnant Sprague-Dawley rats were raised in one of the
      following rearing conditions: in total darkness and enriched environment
      conditions with physical exercise, and in total darkness with voluntary physical
      exercise. Astrocytic density was estimated by immunohistochemistry for S-100beta
      protein and quantifications were performed in layer IV. The somatosensorial
      cortex barrel field was also studied as control. Our main result shows that an
      enriched environment combined with voluntary physical exercise manages to reverse
      the negative effects induced by darkness over the astroglial population of both
      the visual and the somatosensory cortices. On the other hand, exercise alone only
      produces effects upon the astroglial population of the somatosensory cortex, and
      less so when combined with an enriched environment. 

PMID- 24109432
TI  - MicroRNA regulation and dysregulation in epilepsy.
AB  - Epilepsy, one of the most frequent neurological disorders, represents a group of
      diseases that have in common the clinical occurrence of seizures. The
      pathogenesis of different types of epilepsy involves many important biological
      pathways; some of which have been shown to be regulated by microRNAs (miRNAs). In
      this paper, we will critically review relevant studies regarding the role of
      miRNAs in epilepsy. Overall, the most common type of epilepsy in the adult
      population is temporal lobe epilepsy (TLE), and the form associated with mesial
      temporal sclerosis (MTS), called mesial TLE, is particularly relevant due to the
      high frequency of resistance to clinical treatment. There are several target
      studies, as well few genome-wide miRNA expression profiling studies reporting
      abnormal miRNA expression in tissue with MTS, both in patients and in animal
      models. Overall, these studies show a fine correlation between miRNA
      regulation/dysregulation and inflammation, seizure-induced neuronal death and
      other relevant biological pathways. Furthermore, expression of many miRNAs is
      dynamically regulated during neurogenesis and its dysregulation may play a role
      in the process of cerebral corticogenesis leading to malformations of cortical
      development (MCD), which represent one of the major causes of drug-resistant
      epilepsy. In addition, there are reports of miRNAs involved in cell
      proliferation, fate specification, and neuronal maturation and these processes
      are tightly linked to the pathogenesis of MCD. Large-scale analyzes of miRNA
      expression in animal models with induced status epilepticus have demonstrated
      changes in a selected group of miRNAs thought to be involved in the regulation of
      cell death, synaptic reorganization, neuroinflammation, and neural excitability.
      In addition, knocking-down specific miRNAs in these animals have demonstrated
      that this may consist in a promising therapeutic intervention. 

PMID- 24109433
TI  - Comparative neuronal differentiation of self-renewing neural progenitor cell
      lines obtained from human induced pluripotent stem cells.
AB  - Most human neuronal disorders are associated with genetic alterations that cause
      defects in neuronal development and induce precocious neurodegeneration. In order
      to fully characterize the molecular mechanisms underlying the onset of these
      devastating diseases, it is important to establish in vitro models able to
      recapitulate the human pathology as closely as possible. Here we compared three
      different differentiation protocols for obtaining functional neurons from human
      induced pluripotent stem cells (hiPSCs): human neural progenitors (hNPs) obtained
      from hiPSCs were differentiated by co-culturing them with rat primary neurons,
      glial cells or simply by culturing them on matrigel in neuronal differentiation
      medium, and the differentiation level was compared using immunofluorescence,
      biochemical and electrophysiological methods. We show that the differentiated
      neurons displayed distinct maturation properties depending on the protocol used
      and the faster morphological and functional maturation was obtained when hNPs
      were co-cultured with rat primary neurons. 

PMID- 24109434
TI  - IP3R1 deficiency in the cerebellum/brainstem causes basal ganglia-independent
      dystonia by triggering tonic Purkinje cell firings in mice.
AB  - The type 1 inositol 1,4,5- trisphosphate receptor (IP3R1) is a Ca(2+) channel on
      the endoplasmic reticulum and is a predominant isoform in the brain among the
      three types of IP3Rs. Mice lacking IP3R1 show seizure-like behavior; however the
      cellular and neural circuit mechanism by which IP3R1 deletion causes the abnormal
      movements is unknown. Here, we found that the conditional knockout mice lacking
      IP3R1 specifically in the cerebellum and brainstem experience dystonia and show
      that cerebellar Purkinje cell (PC) firing patterns were coupled to specific
      dystonic movements. Recordings in freely behaving mice revealed epochs of low and
      high frequency PC complex spikes linked to body extension and rigidity,
      respectively. Remarkably, dystonic symptoms were independent of the basal
      ganglia, and could be rescued by inactivation of the cerebellum, inferior olive
      or in the absence of PCs. These findings implicate IP3R1-dependent PC firing
      patterns in cerebellum in motor coordination and the expression of dystonia
      through the olivo-cerebellar pathway. 

PMID- 24109435
TI  - Brain anatomy of the marine isopod Saduria entomon Linnaeus, 1758 (Valvifera,
      Isopoda) with special emphasis on the olfactory pathway.
AB  - Representatives of at least six crustacean taxa managed to establish a
      terrestrial life style during their evolutionary history and the Oniscidea
      (Isopoda) are currently held as the most successfully terrestrialized
      malacostracan crustaceans. The brain architecture of terrestrial isopods is
      fairly well understood and studies on this field suggest that the evolutionary
      transition from sea to land in isopods coincided with a considerable size
      reduction and functional loss of their first pair of antennae and associated
      brain areas. This finding suggests that terrestrial isopods may have no or poor
      abilities to detect volatile substances but that their chemosensory ecology is
      most likely restricted to contact chemoreception. In this study, we explored how
      the brain of a marine isopod and particularly its olfactory system compares to
      that of terrestrial relatives. Using histochemical and immunohistochemical
      labeling, brightfield and confocal laser-scan microscopy, we show that in the
      marine isopod Saduria entomon aesthetascs on the first pair of antennae provide
      input to a well defined deutocerebrum (DC). The deutocerebral chemosensory lobes
      (DCL) are divided into spherical neuropil compartments, the olfactory glomeruli
      (og). Secondary processing areas in the lateral protocerebrum (lPC) are supplied
      by a thin but distinct projection neuron tract (PNT) with a contralateral
      connection. Hence, contrary to terrestrial Isopoda, S. entomon has at least the
      neuronal substrate to perceive and process olfactory stimuli suggesting the
      originally marine isopod lineage had olfactory abilities comparable to that of
      other malacostracan crustaceans. 

PMID- 24109436
TI  - Toward a common theory for learning from reward, affect, and motivation: the
      SIMON framework.
AB  - While the effects of reward, affect, and motivation on learning have each
      developed into their own fields of research, they largely have been investigated
      in isolation. As all three of these constructs are highly related, and use
      similar experimental procedures, an important advance in research would be to
      consider the interplay between these constructs. Here we first define each of the
      three constructs, and then discuss how they may influence each other within a
      common framework. Finally, we delineate several sources of evidence supporting
      the framework. By considering the constructs of reward, affect, and motivation
      within a single framework, we can develop a better understanding of the processes
      involved in learning and how they interplay, and work toward a comprehensive
      theory that encompasses reward, affect, and motivation. 

PMID- 24109437
TI  - Synchrony in Parkinson's disease: importance of intrinsic properties of the
      external globus pallidus.
AB  - The mechanisms for the emergence and transmission of synchronized oscillations in
      Parkinson's disease, which are potentially causal to motor deficits, remain
      debated. Aside from the motor cortex and the subthalamic nucleus, the external
      globus pallidus (GPe) has been shown to be essential for the maintenance of these
      oscillations and plays a major role in sculpting neural network activity in the
      basal ganglia (BG). While neural activity of the healthy GPe shows almost no
      correlations between pairs of neurons, prominent synchronization in the beta
      frequency band arises after dopamine depletion. Several studies have proposed
      that this shift is due to network interactions between the different BG nuclei,
      including the GPe. However, recent studies demonstrate an important role for the
      properties of neurons within the GPe. In this review, we will discuss these
      intrinsic GPe properties and review proposed mechanisms for activity
      decorrelation within the dopamine-intact GPe. Failure of the GPe to desynchronize
      correlated inputs can be a possible explanation for synchronization in the whole
      BG. Potential triggers of synchronization involve the enhancement of GPe-GPe
      inhibition and changes in ion channel function in GPe neurons. 

PMID- 24109438
TI  - The role of frontostriatal impairment in freezing of gait in Parkinson's disease.
AB  - Freezing of gait (FOG) is a disabling symptom of advanced Parkinson's disease
      (PD) that leads to an increased risk of falls and nursing home placement.
      Interestingly, multiple lines of evidence suggest that the manifestation of FOG
      is related to specific deficits in cognition, such as set shifting and the
      ability to process conflict-related signals. These findings are consistent with
      the specific patterns of abnormal cortical processing seen during functional
      neuroimaging experiments of FOG, implicating increased neural activation within
      cortical structures underlying cognition, such as the Cognitive Control Network.
      In addition, these studies show that freezing episodes are associated with
      abnormalities in the BOLD response within key structures of the basal ganglia,
      such as the striatum and the subthalamic nucleus. In this article, we discuss the
      implications of these findings on current models of freezing behavior and propose
      an updated model of basal ganglia impairment during FOG episodes that integrates
      the neural substrates of freezing from the cortex and the basal ganglia to the
      cognitive dysfunctions inherent in the condition. 

PMID- 24109439
TI  - Duration differences of corticostriatal responses in striatal projection neurons
      depend on calcium activated potassium currents.
AB  - The firing of striatal projection neurons (SPNs) exhibits afterhyperpolarizing
      potentials (AHPs) that determine discharge frequency. They are in part generated
      by Ca(2+)-activated K(+)-currents involving BK and SK components. It has
      previously been shown that suprathreshold corticostriatal responses are more
      prolonged and evoke more action potentials in direct pathway SPNs (dSPNs) than in
      indirect pathway SPNs (iSPNs). In contrast, iSPNs generate dendritic
      autoregenerative responses. Using whole cell recordings in brain slices, we asked
      whether the participation of Ca(2+)-activated K(+)-currents plays a role in these
      responses. Secondly, we asked if these currents may explain some differences in
      synaptic integration between dSPNs and iSPNs. Neurons obtained from BAC D1 and D2
      GFP mice were recorded. We used charybdotoxin and apamin to block BK and SK
      channels, respectively. Both antagonists increased the depolarization and delayed
      the repolarization of suprathreshold corticostriatal responses in both neuron
      classes. We also used NS 1619 and NS 309 (CyPPA), to enhance BK and SK channels,
      respectively. Current enhancers hyperpolarized and accelerated the repolarization
      of corticostriatal responses in both neuron classes. Nevertheless, these drugs
      made evident that the contribution of Ca(2+)-activated K(+)-currents was
      different in dSPNs as compared to iSPNs: in dSPNs their activation was slower as
      though calcium took a diffusion delay to activate them. In contrast, their
      activation was fast and then sustained in iSPNs as though calcium flux activates
      them at the moment of entry. The blockade of Ca(2+)-activated K(+)-currents made
      iSPNs to look as dSPNs. Conversely, their enhancement made dSPNs to look as
      iSPNs. It is concluded that Ca(2+)-activated K(+)-currents are a main intrinsic
      determinant causing the differences in synaptic integration between
      corticostriatal polysynaptic responses between dSPNs and iSPNs. 

PMID- 24109440
TI  - The microbiota-gut-brain axis: neurobehavioral correlates, health and sociality.
AB  - Recent data suggest that the human body is not such a neatly self-sufficient
      island after all. It is more like a super-complex ecosystem containing trillions
      of bacteria and other microorganisms that inhabit all our surfaces; skin, mouth,
      sexual organs, and specially intestines. It has recently become evident that such
      microbiota, specifically within the gut, can greatly influence many physiological
      parameters, including cognitive functions, such as learning, memory and decision
      making processes. Human microbiota is a diverse and dynamic ecosystem, which has
      evolved in a mutualistic relationship with its host. Ontogenetically, it is
      vertically inoculated from the mother during birth, established during the first
      year of life and during lifespan, horizontally transferred among relatives, mates
      or close community members. This micro-ecosystem serves the host by protecting it
      against pathogens, metabolizing complex lipids and polysaccharides that otherwise
      would be inaccessible nutrients, neutralizing drugs and carcinogens, modulating
      intestinal motility, and making visceral perception possible. It is now evident
      that the bidirectional signaling between the gastrointestinal tract and the
      brain, mainly through the vagus nerve, the so called "microbiota-gut-vagus-brain
      axis," is vital for maintaining homeostasis and it may be also involved in the
      etiology of several metabolic and mental dysfunctions/disorders. Here we review
      evidence on the ability of the gut microbiota to communicate with the brain and
      thus modulate behavior, and also elaborate on the ethological and cultural
      strategies of human and non-human primates to select, transfer and eliminate
      microorganisms for selecting the commensal profile. 

PMID- 24109441
TI  - Serotonin enhances solitariness in phase transition of the migratory locust.
AB  - The behavioral plasticity of locusts is a striking trait presented during the
      reversible phase transition between solitary and gregarious individuals. However,
      the results of serotonin as a neurotransmitter from the migratory locust Locusta
      migratoria in phase transition showed an alternative profile compared to the
      results from the desert locust Schistocerca gregaria. In this study, we
      investigated the roles of serotonin in the brain during the phase change of the
      migratory locust. During the isolation of gregarious nymphs, the concentration of
      serotonin in the brain increased significantly, whereas serotonin receptors
      (i.e., 5-HT 1 , 5-HT 2 , and 5-HT 7 ) we identified here showed invariable
      expression patterns. Pharmacological intervention showed that serotonin injection
      in the brain of gregarious nymphs did not induced the behavioral change toward
      solitariness, but injection of this chemical in isolated gregarious nymphs
      accelerated the behavioral change from gregarious to solitary phase. During the
      crowding of solitary nymphs, the concentration of serotonin in the brain remained
      unchanged, whereas 5-HT 2 increased after 1 h of crowding and maintained stable
      expression level thereafter. Activation of serotonin-5-HT2 signaling with a
      pharmaceutical agonist inhibited the gregariousness of solitary nymphs in
      crowding treatment. These results indicate that the fluctuations of serotonin
      content and 5-HT 2 expression are results of locust phase change. Overall, this
      study demonstrates that serotonin enhances the solitariness of the gregarious
      locusts. Serotonin may regulate the withdrawal-like behavioral pattern displayed
      during locust phase change and this mechanism is conserved in different locust
      species. 

PMID- 24109442
TI  - Context prediction analysis and episodic memory.
AB  - Events that happen at a particular place and time come to define our episodic
      memories. Extensive experimental and clinical research illustrate that the
      hippocampus is central to the processing of episodic memories, and this is in
      large part due to its analysis of context information according to spatial and
      temporal references. In this way, hippocampus defines ones expectations for a
      given context as well as detects errors in predicted contextual features. The
      detection of context prediction errors is hypothesized to distinguished events
      into meaningful epochs that come to be recalled as separate episodic memories.
      The nature of the spatial and temporal context information processed by
      hippocampus is described, as is a hypothesis that the apparently self-regulatory
      nature of hippocampal context processing may ultimately be mediated by natural
      homeostatic operations and plasticity. Context prediction errors by hippocampus
      are suggested to be valued by the midbrain dopamine system, the output of which
      is ultimately fed back to hippocampus to update memory-driven context
      expectations for future events. Thus, multiple network functions (both within and
      outside hippocampus) combine to result in adaptive episodic memories. 

PMID- 24109443
TI  - Opioidergic and dopaminergic manipulation of gambling tendencies: a preliminary
      study in male recreational gamblers.
AB  - Gambling is characterized by cognitive distortions in the processing of chance
      and skill that are exacerbated in pathological gambling. Opioid and dopamine
      dysregulation is implicated in pathological gambling, but it is unclear whether
      these neurotransmitters modulate gambling distortions. The objective of the
      current study was to assess the effects of the opioid receptor antagonist
      naltrexone and the dopamine D2 receptor antagonist haloperidol on gambling
      behavior. Male recreational gamblers (n = 62) were assigned to receive single
      oral doses of naltrexone 50 mg, haloperidol 2 mg or placebo, in a parallel-groups
      design. At 2.5 h post-dosing, participants completed a slot machine task to
      elicit monetary wins, "near-misses," and a manipulation of personal choice, and a
      roulette game to elicit two biases in sequential processing, the gambler's
      fallacy and the hot hand belief. Psychophysiological responses (electrodermal
      activity and heart rate) were taken during the slot machine task, and plasma
      prolactin increase was assessed. The tasks successfully induced the gambling
      effects of interest. Some of these effects differed across treatment groups,
      although the direction of effect was not in line with our predictions.
      Differences were driven by the naltrexone group, which displayed a greater
      physiological response to wins, and marginally higher confidence ratings on
      winning streaks. Prolactin levels increased in the naltrexone group, but did not
      differ between haloperidol and placebo, implying that naltrexone but not
      haloperidol may have been functionally active at these doses. Our results support
      opioid modulation of cognition during gambling-like tasks, but did not support
      the more specific hypothesis that naltrexone may act to ameliorate cognitive
      distortions. 

PMID- 24109444
TI  - The time course of reading processes in children with and without dyslexia: an
      ERP study.
AB  - The main diagnostic criterion for developmental dyslexia (DD) in transparent
      orthographies is a remarkable reading speed deficit, which is often accompanied
      by spelling difficulties. These deficits have been traced back to both deficits
      in orthographic and phonological processing. For a better understanding of the
      reading speed deficit in DD it is necessary to clarify which processing steps are
      degraded in children with DD during reading. In order to address this question
      the present study used EEG to investigate three reading related ERPs: the N170,
      N400 and LPC. Twenty-nine children without DD and 52 children with DD performed a
      phonological lexical decision (PLD)-task, which tapped both orthographic and
      phonological processing. Children were presented with words, pseudohomophones,
      pseudowords and false fonts and had to decide whether the presented stimulus
      sounded like an existing German word or not. Compared to control children,
      children with DD showed deficits in all the investigated ERPs. Firstly, a
      diminished mean area under the curve for the word material-false font contrasts
      in the time window of the N170 was observed, indicating a reduced degree of print
      sensitivity; secondly, N400 amplitudes, as suggested to reflect the access to the
      orthographic lexicon and grapheme-phoneme conversion, were attenuated; and
      lastly, phonological access as indexed by the LPC was degraded in children with
      DD. Processing differences dependent on the linguistic material in children
      without DD were observed only in the LPC, suggesting that similar reading
      processes were adopted independent of orthographic familiarity. The results of
      this study suggest that effective treatment should include both orthographic and
      phonological training. Furthermore, more longitudinal studies utilizing the same
      task and stimuli are needed to clarify how these processing steps and their time
      course change during reading development. 

PMID- 24109445
TI  - Predicting the behavioral impact of transcranial direct current stimulation:
      issues and limitations.
AB  - The transcranial application of weak currents to the human brain has enjoyed a
      decade of widespread use, providing a simple and powerful tool for non-invasively
      altering human brain function. However, our understanding of current delivery and
      its impact upon neural circuitry leaves much to be desired. We argue that the
      credibility of conclusions drawn with transcranial direct current stimulation
      (tDCS) is contingent upon realistic explanations of how tDCS works, and that our
      present understanding of tDCS limits the technique's use to localize function in
      the human brain. We outline two central issues where progress is required: the
      localization of currents, and predicting their functional consequence. We
      encourage experimenters to eschew simplistic explanations of mechanisms of
      transcranial current stimulation. We suggest the use of individualized current
      modeling, together with computational neurostimulation to inform mechanistic
      frameworks in which to interpret the physiological impact of tDCS. We hope that
      through mechanistically richer descriptions of current flow and action, insight
      into the biological processes by which transcranial currents influence behavior
      can be gained, leading to more effective stimulation protocols and empowering
      conclusions drawn with tDCS. 

PMID- 24109446
TI  - Physiological noise in brainstem FMRI.
AB  - The brainstem is directly involved in controlling blood pressure, respiration,
      sleep/wake cycles, pain modulation, motor, and cardiac output. As such it is of
      significant basic science and clinical interest. However, the brainstem's
      location close to major arteries and adjacent pulsatile cerebrospinal fluid
      filled spaces, means that it is difficult to reliably record functional magnetic
      resonance imaging (fMRI) data from. These physiological sources of noise generate
      time varying signals in fMRI data, which if left uncorrected can obscure signals
      of interest. In this Methods Article we will provide a practical introduction to
      the techniques used to correct for the presence of physiological noise in time
      series fMRI data. Techniques based on independent measurement of the cardiac and
      respiratory cycles, such as retrospective image correction (RETROICOR, Glover et
      al., 2000), will be described and their application and limitations discussed.
      The impact of a physiological noise model, implemented in the framework of the
      general linear model, on resting fMRI data acquired at 3 and 7 T is presented.
      Data driven approaches based such as independent component analysis (ICA) are
      described. MR acquisition strategies that attempt to either minimize the
      influence of physiological fluctuations on recorded fMRI data, or provide
      additional information to correct for their presence, will be mentioned. General
      advice on modeling noise sources, and its effect on statistical inference via
      loss of degrees of freedom, and non-orthogonality of regressors, is given.
      Lastly, different strategies for assessing the benefit of different approaches to
      physiological noise modeling are presented. 

PMID- 24109447
TI  - The role of accent imitation in sensorimotor integration during processing of
      intelligible speech.
AB  - Recent theories on how listeners maintain perceptual invariance despite variation
      in the speech signal allocate a prominent role to imitation mechanisms. Notably,
      these simulation accounts propose that motor mechanisms support perception of
      ambiguous or noisy signals. Indeed, imitation of ambiguous signals, e.g.,
      accented speech, has been found to aid effective speech comprehension. Here, we
      explored the possibility that imitation in speech benefits perception by
      increasing activation in speech perception and production areas. Participants
      rated the intelligibility of sentences spoken in an unfamiliar accent of Dutch in
      a functional Magnetic Resonance Imaging experiment. Next, participants in one
      group repeated the sentences in their own accent, while a second group vocally
      imitated the accent. Finally, both groups rated the intelligibility of accented
      sentences in a post-test. The neuroimaging results showed an interaction between
      type of training and pre- and post-test sessions in left Inferior Frontal Gyrus,
      Supplementary Motor Area, and left Superior Temporal Sulcus. Although alternative
      explanations such as task engagement and fatigue need to be considered as well,
      the results suggest that imitation may aid effective speech comprehension by
      supporting sensorimotor integration. 

PMID- 24109448
TI  - Phase-amplitude cross-frequency coupling in the human nucleus accumbens tracks
      action monitoring during cognitive control.
AB  - The Nucleus Accumbens (NAcc) is an important structure for the transfer of
      information between cortical and subcortical structures, especially the
      prefrontal cortex and the hippocampus. However, the mechanism that allows the
      NAcc to achieve this integration is not well understood. Phase-amplitude cross
      frequency coupling (PAC) of oscillations in different frequency bands has been
      proposed as an effective mechanism to form functional networks to optimize
      transfer and integration of information. Here we assess PAC between theta and
      high gamma oscillations as a potential mechanism that facilitates motor
      adaptation. To address this issue we recorded intracranial field potentials
      directly from the bilateral human NAcc in three patients while they performed a
      motor learning task that varied in the level of cognitive control needed to
      perform the task. As in rodents, PAC was observable in the human NAcc,
      transiently occurring contralateral to a movement following the motor response.
      Importantly, PAC correlated with the level of cognitive control needed to monitor
      the action performed. This functional relation indicates that the NAcc is engaged
      in action monitoring and supports the evaluation of motor programs during
      adaptive behavior by means of PAC. 

PMID- 24109449
TI  - Ten year neurocognitive trajectories in first-episode psychosis.
AB  - OBJECTIVE: Neurocognitive impairment is commonly reported at onset of psychotic
      disorders. However, the long-term neurocognitive course remains largely
      uninvestigated in first episode psychosis (FEP) and the relationship to
      clinically significant subgroups even more so. We report 10 year longitudinal
      neurocognitive development in a sample of FEP patients, and explore whether the
      trajectories of cognitive course are related to presence of relapse to psychosis,
      especially within the first year, with a focus on the course of verbal memory.
      METHOD: Forty-three FEP subjects (51% male, 28 +/- 9 years) were followed-up
      neurocognitively over five assessments spanning 10 years. The test battery was
      divided into four neurocognitive indices; Executive Function, Verbal Learning,
      Motor Speed, and Verbal Fluency. The sample was grouped into those relapsing or
      not within the first, second and fifth year. RESULTS: The four neurocognitive
      indices showed overall stability over the 10 year period. Significant relapse by
      index interactions were found for all indices except Executive Function. Follow
      up analyses identified a larger significant decrease over time for the encoding
      measure within Verbal Memory for patients with psychotic relapse in the first
      year [F (4, 38) = 5.8, p = 0.001, eta(2) = 0.40]. CONCLUSIONS: Main findings are
      long-term stability in neurocognitive functioning in FEP patients, with the
      exception of verbal memory in patients with psychotic relapse or non-remission
      early in the course of illness. We conclude that worsening of specific parts of
      cognitive function may be expected for patients with on-going psychosis, but that
      the majority of patients do not show significant change in cognitive performance
      during the first 10 years after being diagnosed.

PMID- 24109450
TI  - Effects of social intention on movement kinematics in cooperative actions.
AB  - Optimal control models of biological movements are used to account for those
      internal variables that constrain voluntary goal-directed actions. They, however,
      do not take into account external environmental constraints as those associated
      to social intention. We investigated here the effects of the social context on
      kinematic characteristics of sequential actions consisting in placing an object
      on an initial pad (preparatory action) before reaching and grasping as fast as
      possible the object to move it to another location (main action). Reach-to-grasp
      actions were performed either in an isolated condition or in the presence of a
      partner (audience effect), located in the near or far space (effect of shared
      reachable space), and who could intervene on the object in a systematic fashion
      (effect of social intention effect) or not (effect of social uncertainty).
      Results showed an absence of audience effect but nevertheless an influence of the
      social context both on the main and the preparatory actions. In particular, a
      "localized" effect of shared reachable space was observed on the main action,
      which was smoother when performed within the reachable space of the partner.
      Furthermore, a "global" effect of social uncertainty was observed on both actions
      with faster and jerkier movements. Finally, social intention affected the
      preparatory action with higher wrist displacements and slower movements when the
      object was placed for the partner rather than placed for self-use. Overall, these
      results demonstrate specific effects of action space, social uncertainty and
      social intention on the planning of reach-to-grasp actions, in particular on the
      preparatory action, which was performed with no specific execution constraint.
      These findings underline the importance of considering the social context in
      optimal models of action control for human-robot interactions, in particular when
      focusing on the implementation of motor parameters required to afford intuitive
      interactions. 

PMID- 24109451
TI  - Learning indoor robot navigation using visual and sensorimotor map information.
AB  - As a fundamental research topic, autonomous indoor robot navigation continues to
      be a challenge in unconstrained real-world indoor environments. Although many
      models for map-building and planning exist, it is difficult to integrate them due
      to the high amount of noise, dynamics, and complexity. Addressing this challenge,
      this paper describes a neural model for environment mapping and robot navigation
      based on learning spatial knowledge. Considering that a person typically moves
      within a room without colliding with objects, this model learns the spatial
      knowledge by observing the person's movement using a ceiling-mounted camera. A
      robot can plan and navigate to any given position in the room based on the
      acquired map, and adapt it based on having identified possible obstacles. In
      addition, salient visual features are learned and stored in the map during
      navigation. This anchoring of visual features in the map enables the robot to
      find and navigate to a target object by showing an image of it. We implement this
      model on a humanoid robot and tests are conducted in a home-like environment.
      Results of our experiments show that the learned sensorimotor map masters complex
      navigation tasks. 

PMID- 24109453
TI  - Targeting sites of inflammation: intercellular adhesion molecule-1 as a target
      for novel inflammatory therapies.
AB  - Targeted drug delivery to sites of inflammation will provide effective, precise,
      and safe therapeutic interventions for treatment of diverse disease conditions,
      by limiting toxic side effects and/or increasing drug action. Disease-site
      targeting is believed to play a major role in the enhanced efficacy observed for
      a variety of drugs when formulated inside lipid vesicles. This article will focus
      on the factors and mechanisms involved in drug targeting to sites of inflammation
      and the importance of cell adhesion molecules, in particular intercellular
      adhesion molecule-1, in this process. 

PMID- 24109452
TI  - Insights into the metabolic response to traumatic brain injury as revealed by
      (13)C NMR spectroscopy.
AB  - The present review highlights critical issues related to cerebral metabolism
      following traumatic brain injury (TBI) and the use of (13)C labeled substrates
      and nuclear magnetic resonance (NMR) spectroscopy to study these changes. First
      we address some pathophysiologic factors contributing to metabolic dysfunction
      following TBI. We then examine how (13)C NMR spectroscopy strategies have been
      used to investigate energy metabolism, neurotransmission, the intracellular redox
      state, and neuroglial compartmentation following injury. (13)C NMR spectroscopy
      studies of brain extracts from animal models of TBI have revealed enhanced
      glycolytic production of lactate, evidence of pentose phosphate pathway (PPP)
      activation, and alterations in neuronal and astrocyte oxidative metabolism that
      are dependent on injury severity. Differential incorporation of label into
      glutamate and glutamine from (13)C labeled glucose or acetate also suggest TBI
      induced adaptations to the glutamate-glutamine cycle. 

PMID- 24109454
TI  - Multifractal detrended fluctuation analysis of human gait diseases.
AB  - In this paper multifractal detrended fluctuation analysis (MFDFA) is used to
      study the human gait time series for normal and diseased sets. It is observed
      that long range correlation is primarily responsible for the origin of
      multifractality. The study reveals that the degree of multifractality is more for
      normal set compared to diseased set. However, the method fails to distinguish
      between the two diseased sets. 

PMID- 24109455
TI  - Functional effects of KCNQ K(+) channels in airway smooth muscle.
AB  - KCNQ (Kv7) channels underlie a voltage-gated K(+) current best known for control
      of neuronal excitability, and its inhibition by Gq/11-coupled, muscarinic
      signaling. Studies have indicated expression of KCNQ channels in airway smooth
      muscle (ASM), a tissue that is predominantly regulated by muscarinic receptor
      signaling. Therefore, we investigated the function of KCNQ channels in rodent ASM
      and their interplay with Gq/11-coupled M3 muscarinic receptors. Perforated-patch
      clamp of dissociated ASM cells detected a K(+) current inhibited by the KCNQ
      antagonist, XE991, and augmented by the specific agonist, flupirtine. KCNQ
      channels begin to activate at voltages near resting potentials for ASM cells, and
      indeed XE991 depolarized resting membrane potentials. Muscarinic receptor
      activation inhibited KCNQ current weakly (~20%) at concentrations half-maximal
      for contractions. Thus, we were surprised to see that KCNQ had no affect on
      membrane voltage or muscle contractility following muscarinic activation.
      Further, M3 receptor-specific antagonist J104129 fumarate alone did not reveal
      KCNQ effects on muscarinic evoked depolarization or contractility. However, a
      role for KCNQ channels was revealed when BK-K(+) channel activities are reduced.
      While KCNQ channels do control resting potentials, they appear to play a
      redundant role with BK calcium-activated K(+) channels during ASM muscarinic
      signaling. In contrast to effect of antagonist, we observe that KCNQ agonist
      flupirtine caused a significant hyperpolarization and reduced contraction in
      vitro irrespective of muscarinic activation. Using non-invasive whole animal
      plethysmography, the clinically approved KCNQ agonist retigabine caused a
      transient reduction in indexes of airway resistance in both wild type and BK
      beta1 knockout (KO) mice treated with the muscarinic agonist. These findings
      indicate that KCNQ channels can be recruited via agonists to oppose muscarinic
      evoked contractions and may be of therapeutic value as bronchodilators. 

PMID- 24109456
TI  - Mathematical biomarkers for the autonomic regulation of cardiovascular system.
AB  - Heart rate and blood pressure are the most important vital signs in diagnosing
      disease. Both heart rate and blood pressure are characterized by a high degree of
      short term variability from moment to moment, medium term over the normal day and
      night as well as in the very long term over months to years. The study of new
      mathematical algorithms to evaluate the variability of these cardiovascular
      parameters has a high potential in the development of new methods for early
      detection of cardiovascular disease, to establish differential diagnosis with
      possible therapeutic consequences. The autonomic nervous system is a major player
      in the general adaptive reaction to stress and disease. The quantitative
      prediction of the autonomic interactions in multiple control loops pathways of
      cardiovascular system is directly applicable to clinical situations. Exploration
      of new multimodal analytical techniques for the variability of cardiovascular
      system may detect new approaches for deterministic parameter identification. A
      multimodal analysis of cardiovascular signals can be studied by evaluating their
      amplitudes, phases, time domain patterns, and sensitivity to imposed stimuli,
      i.e., drugs blocking the autonomic system. The causal effects, gains, and dynamic
      relationships may be studied through dynamical fuzzy logic models, such as the
      discrete-time model and discrete-event model. We expect an increase in accuracy
      of modeling and a better estimation of the heart rate and blood pressure time
      series, which could be of benefit for intelligent patient monitoring. We foresee
      that identifying quantitative mathematical biomarkers for autonomic nervous
      system will allow individual therapy adjustments to aim at the most favorable
      sympathetic-parasympathetic balance. 

PMID- 24109457
TI  - Impairments of motor-cortex responses to unilateral and bilateral direct current
      stimulation in schizophrenia.
AB  - Transcranial direct current stimulation (tDCS) is a non-invasive stimulation
      technique that can be applied to modulate cortical activity through induction of
      cortical plasticity. Since various neuropsychiatric disorders are characterized
      by fluctuations in cortical activity levels (e.g., schizophrenia), tDCS is
      increasingly investigated as a treatment tool. Several studies have shown that
      the induction of cortical plasticity following classical, unilateral tDCS is
      reduced or impaired in the stimulated and non-stimulated primary motor cortices
      (M1) of patients with schizophrenia. Moreover, an alternative, bilateral tDCS
      setup has recently been shown to modulate cortical plasticity in both hemispheres
      in healthy subjects, highlighting another potential treatment approach. Here we
      present the first study comparing the efficacy of unilateral tDCS (cathode left
      M1, anode right supraorbital) with simultaneous bilateral tDCS (cathode left M1,
      anode right M1) in patients with schizophrenia. tDCS-induced cortical plasticity
      was monitored by investigating motor-evoked potentials induced by single-pulse
      transcranial magnetic stimulation applied to both hemispheres. Healthy subjects
      showed a reduction of left M1 excitability following unilateral tDCS on the
      stimulated left hemisphere and an increase in right M1 excitability following
      bilateral tDCS. In schizophrenia, no plasticity was induced following both
      stimulation paradigms. The pattern of these results indicates a complex interplay
      between plasticity and connectivity that is impaired in patients with
      schizophrenia. Further studies are needed to clarify the biological underpinnings
      and clinical impact of these findings. 

PMID- 24109458
TI  - Addiction is Not a Natural Kind.
AB  - I argue that addiction is not an appropriate category to support generalizations
      for the purposes of scientific prediction. That is, addiction is not a natural
      kind. I discuss the Homeostatic Property Cluster (HPC) theory of kinds, according
      to which members of a kind share a cluster of properties generated by a common
      mechanism or set of mechanisms. Leading accounts of addiction in literature fail
      to offer a mechanism that explains addiction across substances. I discuss popular
      variants of the disease conception and demonstrate that at least one class of
      substances that fails to confirm a major prediction of each account. When no
      mechanism can be found to explain the occurrence of the relevant properties in
      members of a category, the HPC view suggests that we revise our categories. I
      discuss options offered by the HPC view, including category revision and category
      replacement. I then conclude that talk of addiction as a prediction-supporting
      category should be replaced with categories such as "S-addiction" and "T
      addiction," where S and T are substances or sets of substances of abuse, as these
      categories are genuine natural kinds. 

PMID- 24109459
TI  - Differential pharmacological effects on brain reactivity and plasticity in
      Alzheimer's disease.
AB  - Acetylcholinesterase inhibitors (AChEIs) are the most commonly prescribed
      monotherapeutic medications for Alzheimer's disease (AD). However, their
      underlying neurophysiological effects remain largely unknown. We investigated the
      effects of monotherapy (AChEI) and combination therapy (AChEI and memantine) on
      brain reactivity and plasticity. Patients treated with monotherapy (AChEI) (N =
      7) were compared to patients receiving combination therapy (COM) (N = 9) and a
      group of age-matched, healthy controls (HCs) (N = 13). Cortical reactivity and
      plasticity of the motor cortex were examined using transcranial magnetic
      stimulation. Cognitive functions were assessed with the cognitive subscale of the
      Alzheimer Disease Assessment Scale-Cognitive Subscale (ADAS-Cog), activities of
      daily living (ADLs) with the ADCS-ADL. In addition we assessed the degree of
      brain atrophy by measuring brain-scalp distances in seven different brain areas.
      Patient groups differed in resting motor threshold and brain atrophy, with COM
      showing a lower motor threshold but less atrophy than AChEI. COM showed similar
      plasticity effects as the HC group, while plasticity was reduced in AChEI. Long
      interval intracortical inhibition (LICI) was impaired in both patient groups when
      compared to HC. ADAS-Cog scores were positively correlated with LICI measures and
      with brain atrophy, specifically in the left inferior parietal cortex. AD
      patients treated with mono- or combination-therapy show distinct
      neurophysiological patterns. Further studies should investigate whether these
      measures might serve as biomarkers of treatment response and whether they could
      guide other therapeutic interventions. 

PMID- 24109461
TI  - A computational model to investigate assumptions in the headturn preference
      procedure.
AB  - In this paper we use a computational model to investigate four assumptions that
      are tacitly present in interpreting the results of studies on infants' speech
      processing abilities using the Headturn Preference Procedure (HPP): (1)
      behavioral differences originate in different processing; (2) processing involves
      some form of recognition; (3) words are segmented from connected speech; and (4)
      differences between infants should not affect overall results. In addition, we
      investigate the impact of two potentially important aspects in the design and
      execution of the experiments: (a) the specific voices used in the two parts on
      HPP experiments (familiarization and test) and (b) the experimenter's criterion
      for what is a sufficient headturn angle. The model is designed to be maximize
      cognitive plausibility. It takes real speech as input, and it contains a module
      that converts the output of internal speech processing and recognition into
      headturns that can yield real-time listening preference measurements. Internal
      processing is based on distributed episodic representations in combination with a
      matching procedure based on the assumptions that complex episodes can be
      decomposed as positive weighted sums of simpler constituents. Model simulations
      show that the first assumptions hold under two different definitions of
      recognition. However, explicit segmentation is not necessary to simulate the
      behaviors observed in infant studies. Differences in attention span between
      infants can affect the outcomes of an experiment. The same holds for the
      experimenter's decision criterion. The speakers used in experiments affect
      outcomes in complex ways that require further investigation. The paper ends with
      recommendations for future studies using the HPP. 

PMID- 24109462
TI  - Learning on the IGT follows emergence of knowledge but not differential somatic
      activity.
AB  - The importance of unconscious autonomic activity vs. knowledge in influencing
      behavior on the Iowa Gambling Task (IGT) has been the subject of debate. The
      task's developers, Bechara and colleagues, have claimed that behavior on the IGT
      is influenced by somatic activity and that this activity precedes the emergence
      of knowledge about the task contingencies sufficient to guide behavior. Since
      then others have claimed that this knowledge emerges much earlier on the task.
      However, it has yet to be established whether somatic activity which
      differentiates between advantageous and disadvantageous choices on the IGT is
      found before this point. This study describes an experiment to determine whether
      knowledge sufficient to guide behavior precedes differential autonomic activity
      or vice versa. This experiment used a computerized version of the IGT, knowledge
      probes after every 10 trials and skin conductance recording to measure somatic
      activity. Whereas in previous reports the majority of participants end the task
      with full conceptual knowledge of the IGT contingencies we found little evidence
      in support of this conclusion. However, full conceptual knowledge was not
      critical for advantageous deck selection to occur and most participants had
      knowledge sufficient to guide behavior after approximately 40 trials. We did not
      find anticipatory physiological activity sufficient to differentiate between deck
      types in the period prior to acquiring this knowledge. However, post-punishment
      physiological activity was found to be larger for the disadvantageous decks in
      the pre-knowledge period, but only for participants who displayed knowledge. Post
      reward physiological activity distinguished between the advantageous and
      disadvantageous decks across the whole experiment but, again, only in
      participants who displayed knowledge and then only in later trials following
      their display of knowledge. 

PMID- 24109463
TI  - Meditation and neurofeedback.

PMID- 24109464
TI  - Children benefit from morphological relatedness when they learn to spell new
      words.
AB  - Use of morphologically related words often helps in selecting among spellings of
      sounds in French. For instance, final /wa/ may be spelled oi (e.g., envoi
      "sendoff"), oit (e.g., exploit "exploit"), ois (e.g., siamois, "siamese"), or oie
      (e.g., joie "joy"). The morphologically complex word exploiter "to exploit", with
      a pronounced t, can be used to indicate that the stem exploit is spelled with a
      silent t. We asked whether 8-year-old children benefited from such cues to learn
      new spellings. Children read silently stories which included two target nonwords,
      one presented in an opaque condition and the other in a morphological condition.
      In the opaque condition, the sentence provided semantic information (e.g., a
      vensois is a musical instrument) but no morphological information that could
      justify the spelling of the target word's final sound. Such justification was
      available in the morphological condition (e.g., the vensoisist plays the vensois
      instrument, which justifies that vensois includes a final silent s). 30 min after
      having read the stories, children's orthographic learning was assessed by asking
      them to choose the correct spelling of each nonword from among three
      phonologically plausible alternatives (e.g., vensois, vensoit, vensoie). Children
      chose correct spellings more often in the morphological condition than the opaque
      condition, even though the root (vensois) had been presented equally often in
      both conditions. That is, children benefited from information about the spelling
      of the morphologically complex word to learn the spelling of the stem. 

PMID- 24109460
TI  - The evolutionary and genetic origins of consciousness in the Cambrian Period over
      500 million years ago.
AB  - Vertebrates evolved in the Cambrian Period before 520 million years ago, but we
      do not know when or how consciousness arose in the history of the vertebrate
      brain. Here we propose multiple levels of isomorphic or somatotopic neural
      representations as an objective marker for sensory consciousness. All extant
      vertebrates have these, so we deduce that consciousness extends back to the
      group's origin. The first conscious sense may have been vision. Then vision,
      coupled with additional sensory systems derived from ectodermal placodes and
      neural crest, transformed primitive reflexive systems into image forming brains
      that map and perceive the external world and the body's interior. We posit that
      the minimum requirement for sensory consciousness and qualia is a brain including
      a forebrain (but not necessarily a developed cerebral cortex/pallium), midbrain,
      and hindbrain. This brain must also have (1) hierarchical systems of
      intercommunicating, isomorphically organized, processing nuclei that extensively
      integrate the different senses into representations that emerge in upper levels
      of the neural hierarchy; and (2) a widespread reticular formation that integrates
      the sensory inputs and contributes to attention, awareness, and neural
      synchronization. We propose a two-step evolutionary history, in which the optic
      tectum was the original center of multi-sensory conscious perception (as in fish
      and amphibians: step 1), followed by a gradual shift of this center to the dorsal
      pallium or its cerebral cortex (in mammals, reptiles, birds: step 2). We address
      objections to the hypothesis and call for more studies of fish and amphibians. In
      our view, the lamprey has all the neural requisites and is likely the simplest
      extant vertebrate with sensory consciousness and qualia. Genes that pattern the
      proposed elements of consciousness (isomorphism, neural crest, placodes) have
      been identified in all vertebrates. Thus, consciousness is in the genes, some of
      which are already known. 

PMID- 24109465
TI  - Good things peak in pairs: a note on the bimodality coefficient.

PMID- 24109466
TI  - How does graphotactic knowledge influence children's learning of new spellings?
AB  - TWO EXPERIMENTS INVESTIGATED WHETHER AND HOW THE LEARNING OF SPELLINGS BY FRENCH
      THIRD GRADERS IS INFLUENCED BY TWO GRAPHOTACTIC PATTERNS: consonants cannot
      double in word-initial position (Experiment 1) and consonants cannot double after
      single consonants (Experiment 2). Children silently read meaningful texts that
      contained three types of novel spellings: no doublet (e.g., mupile, guprane),
      doublet in a legal position (e.g., muppile, gupprane), and doublet in an illegal
      position (e.g., mmupile, guprrane). Orthographic learning was assessed with a
      task of spelling to dictation. In both experiments, children recalled items
      without doublets better than items with doublets. In Experiment 1, children
      recalled spellings with a doublet in illegal word-initial position better than
      spellings with a doublet in legal word-medial position, and almost all
      misspellings involved the omission of the doublet. The fact that the graphotactic
      violation in an item like mmupile was in the salient initial position may explain
      why children often remembered both the presence and the position of the doublet.
      In Experiment 2, children recalled non-words with a doublet before a single
      consonant (legal, e.g., gupprane) better than those with a doublet after a single
      consonant (illegal, e.g., guprrane). Omission of the doublet was the most
      frequent error for both types of items. Children also made some transposition
      errors on items with a doublet after a single consonant, recalling for example
      gupprane instead of guprrane. These results suggest that, when a doublet is in
      the hard-to-remember medial position, children sometimes remember that an item
      contains a doublet but not which letter is doubled. Their knowledge that double
      consonants can occur before but not after single consonants leads to
      transposition errors on items like guprrane. These results shed new light on the
      conditions under which children use general knowledge about the graphotactic
      patterns of their writing system to reconstruct spellings. 

PMID- 24109467
TI  - Tonal cues modulate line bisection performance: preliminary evidence for a new
      rehabilitation prospect?
AB  - The effect of the presentation of two different auditory pitches (high and low)
      on manual line-bisection performance was studied to investigate the relationship
      between space and magnitude representations underlying motor acts. Participants
      were asked to mark the midpoint of a given line with a pen while they were
      listening a pitch via headphones. In healthy participants, the effect of the
      presentation order (blocked or alternative way) of auditory stimuli was tested
      (Experiment 1). The results showed no biasing effect of pitch in blocked-order
      presentation, whereas the alternative presentation modulated the line-bisection.
      Lower pitch produced leftward or downward bisection biases whereas higher pitch
      produced rightward or upward biases, suggesting that visuomotor processing can be
      spatially modulated by irrelevant auditory cues. In Experiment 2, the effect of
      such alternative stimulations in line bisection in right brain damaged patients
      with a unilateral neglect and without a neglect was tested. Similar biasing
      effects caused by auditory cues were observed although the white noise
      presentation also affected the patient's performance. Additionally, the effect of
      pitch difference was larger for the neglect patient than for the no-neglect
      patient as well as for healthy participants. The neglect patient's bisection
      performance gradually improved during the experiment and was maintained even
      after 1 week. It is therefore, concluded that auditory cues, characterized by
      both the pitch difference and the dynamic alternation, influence spatial
      representations. The larger biasing effect seen in the neglect patient compared
      to the no-neglect patient and healthy participants suggests that auditory cues
      could modulate the direction of the attentional bias that is characteristic of
      neglect patients. Thus, the alternative presentation of auditory cues could be
      used as rehabilitation for neglect patients. The space-pitch associations are
      discussed in terms of a generalized magnitude system. 

PMID- 24109468
TI  - Dependency-dependent interference: NPI interference, agreement attraction, and
      global pragmatic inferences.
AB  - Previous psycholinguistics studies have shown that when forming a long distance
      dependency in online processing, the parser sometimes accepts a sentence even
      though the required grammatical constraints are only partially met. A mechanistic
      account of how such errors arise sheds light on both the underlying linguistic
      representations involved and the processing mechanisms that put such
      representations together. In the current study, we contrast the negative polarity
      items (NPI) interference effect, as shown by the acceptance of an ungrammatical
      sentence like "The bills that democratic senators have voted for will ever become
      law," with the well-known phenomenon of agreement attraction ("The key to the
      cabinets are ... "). On the surface, these two types of errors look alike and
      thereby can be explained as being driven by the same source: similarity based
      memory interference. However, we argue that the linguistic representations
      involved in NPI licensing are substantially different from those of subject-verb
      agreement, and therefore the interference effects in each domain potentially
      arise from distinct sources. In particular, we show that NPI interference at
      least partially arises from pragmatic inferences. In a self-paced reading study
      with an acceptability judgment task, we showed NPI interference was modulated by
      participants' general pragmatic communicative skills, as quantified by the Autism
      Spectrum Quotient (AQ, Baron-Cohen et al., 2001), especially in offline tasks.
      Participants with more autistic traits were actually less prone to the NPI
      interference effect than those with fewer autistic traits. This result contrasted
      with agreement attraction conditions, which were not influenced by individual
      pragmatic skill differences. We also show that different NPI licensors seem to
      have distinct interference profiles. We discuss two kinds of interference effects
      for NPI licensing: memory-retrieval based and pragmatically triggered. 

PMID- 24109469
TI  - Exploration, novelty, surprise, and free energy minimization.
AB  - This paper reviews recent developments under the free energy principle that
      introduce a normative perspective on classical economic (utilitarian) decision
      making based on (active) Bayesian inference. It has been suggested that the free
      energy principle precludes novelty and complexity, because it assumes that
      biological systems-like ourselves-try to minimize the long-term average of
      surprise to maintain their homeostasis. However, recent formulations show that
      minimizing surprise leads naturally to concepts such as exploration and novelty
      bonuses. In this approach, agents infer a policy that minimizes surprise by
      minimizing the difference (or relative entropy) between likely and desired
      outcomes, which involves both pursuing the goal-state that has the highest
      expected utility (often termed "exploitation") and visiting a number of different
      goal-states ("exploration"). Crucially, the opportunity to visit new states
      increases the value of the current state. Casting decision-making problems within
      a variational framework, therefore, predicts that our behavior is governed by
      both the entropy and expected utility of future states. This dissolves any
      dialectic between minimizing surprise and exploration or novelty seeking. 

PMID- 24109470
TI  - MRI screening for chronic anticoagulation in atrial fibrillation.
AB  - Anticoagulation is highly effective in preventing stroke due to atrial
      fibrillation, but numerous studies have demonstrated low utilization of
      anticoagulation for these patients. Assessment of clinicians' attitudes on this
      topic indicate that fear of intracerebral hemorrhage (ICH), rather than
      appreciation of anticoagulation benefits, largely drives clinical decision-making
      for treatment with anticoagulation in atrial fibrillation. Risk stratification
      strategies have been used for anticoagulation benefits and hemorrhage risk, but
      ICH is not specifically addressed in the commonly used hemorrhage risk
      stratification systems. Cerebral microbleeds are cerebral microscopic hemorrhages
      demonstrable by brain MRI, indicative of prior microhemorrhages, and predictive
      of future risk of ICH. Prevalence of cerebral microbleeds increases with age; and
      cross-sectional and limited prospective studies generally indicate that
      microbleeds confer substantial risk of ICH in patients treated with chronic
      anticoagulation. MRI thus is a readily available and appealing modality that can
      directly assess risk of future ICH in patients receiving anticoagulants for
      atrial fibrillation. Incorporation of MRI into routine practice is, however,
      fraught with difficulties, including the uncertain relationship between number
      and location of microbleeds and ICH risk, as well as cost-effectiveness of MRI. A
      proposed algorithm is provided, and relevant advantages and disadvantages are
      discussed. At present, MRI screening appears most appropriate for a subset of
      atrial fibrillation patients, such as those with intermediate stroke risk, and
      may provide reassurance for clinicians whose concerns for ICH tend to outweigh
      benefits of anticoagulation. 

PMID- 24109471
TI  - Modafinil as a catecholaminergic agent: empirical evidence and unanswered
      questions.
AB  - Modafinil, in its two clinical formulations (Provigil((r)) and Nuvigil((r))), is
      a widely prescribed wake-promoting therapeutic agent. It binds competitively to
      the cell-membrane dopamine (DA) transporter and is dependent on catecholaminergic
      (dopaminergic and adrenergic) signaling for its wake-promoting effects. The
      clinical spectrum of effects for modafinil is distinct from the effects seen with
      other catecholaminergic agents. Relative to other commonly used agents that act
      through catecholaminergic mechanisms, modafinil has a relatively low abuse
      potential, produces wakefulness with an attenuated compensatory sleep recovery
      thereafter, and does not ameliorate cataplexy in narcolepsy. These clinically
      relevant phenomenological differences between modafinil and agents such as
      amphetamines and cocaine do not eliminate catecholaminergic effects as a possible
      mediator of its wake-promoting action; they merely reflect its unique
      pharmacological profile. Modafinil is an exceptionally weak, but apparently very
      selective, DA transporter inhibitor. The pharmacodynamic response to modafinil,
      as measured by DA levels in brain microdialyzate, is protracted relative to other
      agents that act via catecholaminergic mechanisms. The conformational constraints
      on the interaction of modafinil with the DA transporter - and probably, as a
      consequence, its effects on trace amine receptor signaling in the
      catecholaminergic cell - are unique among catecholaminergic agents. These unique
      pharmacological properties of modafinil should be considered both in seeking to
      thoroughly understand its putatively elusive mechanism of action and in the
      design of novel therapeutic agents. 

PMID- 24109472
TI  - Dopaminergic meso-cortical projections to m1: role in motor learning and motor
      cortex plasticity.
AB  - Although the architecture of a dopaminergic (DA) system within the primary motor
      cortex (M1) was well characterized anatomically, its functional significance
      remained obscure for a long time. Recent studies in rats revealed that the
      integrity of DA fibers in M1 is a prerequisite for successful acquisition of
      motor skills. This essential contribution of DA for motor learning is plausible
      as it modulates M1 circuitry at multiple levels thereby promoting plastic changes
      that are required for information storage: at the network level, DA increases
      cortical excitability and enhances the stability of motor maps. At the cellular
      level, DA induces the expression of learning-related genes via the transcription
      factor c-Fos. At the level of synapses, DA is required for the formation of long
      term potentiation, a mechanism that likely is a fingerprint of a motor memory
      trace within M1. DA fibers innervating M1 originate within the midbrain,
      precisely the ventral tegmental area (VTA) and the medial portion of substantia
      nigra (SN). Thus, they could be part of the meso-cortico-limbic pathway - a
      network that provides information about saliency and motivational value of an
      external stimulus and is commonly referred as "reward system." However, the
      behavioral triggers of the release of dopamine in M1 are not yet identified. As
      alterations in DA transmission within M1 occur under various pathological
      conditions such as Parkinson disease or ischemic and traumatic brain injury, a
      deeper understanding of the interaction of VTA/SN and M1 may reveal a deeper
      insight into a large spectrum of neurological disorders. 

PMID- 24109473
TI  - Neuroimaging, biomarkers, and management of dementia with lewy bodies.

PMID- 24109474
TI  - The role of levetiracetam in treatment of seizures in brain tumor patients.
AB  - Levetiracetam, trade name Keppra, is a new second generation antiepileptic drug
      that is being increasingly used in brain tumor patients. In patients suffering
      with brain tumors, seizures are one of the leading neurologic complications being
      seen in more than 30% of patients. Unlike other antiepileptic drugs,
      levetiracetam is proposed to bind to a synaptic vesicle protein inhibiting
      calcium release. Brain tumor patients are frequently on chemotherapy or other
      drugs that induce cytochrome P450, causing significant drug interactions.
      However, levetiracetam does not induce the P450 system and does not exhibit any
      relevant drug interactions. Intravenous delivery is as bioavailable as the oral
      medication allowing it to be used in emergency situations. Levetiracetam is an
      attractive option for brain tumor patients suffering from seizures, but also can
      be used prophylactically in patients with brain tumors, or patients undergoing
      neurological surgery. Emerging studies have also demonstrated that levetiracetam
      can increase the sensitivity of Glioblastoma tumors to the chemotherapy drug
      temozolomide. Levetiracetam is a safe alternative to conventional antiepileptic
      drugs and an emerging tool for brain tumor patients combating seizures. 

PMID- 24109475
TI  - Can Chronic Remote Cortical Hypoperfusion Induced by Thalamic Infarction Cause
      Damage of Tracts Passing through Those Hypoperfused Regions?
AB  - We report the case of a woman presenting with changes on cerebral imaging a year
      and a half after a bi-thalamic (predominantly left-sided) infarction including
      lateral and medial thalamic nuclei. Lateral geniculate body and pulvinar were not
      damaged. Hypoperfusion was observed in left cortical and basal structures. White
      matter FLAIR hyperintense lesions occurred in the left hemisphere and the
      occipital region 1 year and half after stroke. Medial and lateral thalamic nuclei
      are not highly connected to the occipital cortex. Therefore, in addition to
      Wallerian degeneration after thalamic stroke, we hypothesize that the chronic
      left temporal hypoperfusion induced by diaschisis can lead to a lateralized
      chronic hypoxic damage of the occipital fiber tract (optic radiation) that passes
      through the temporal lobe. 

PMID- 24109477
TI  - Quantitative and phylogenetic study of the Deep Sea Archaeal Group in sediments
      of the Arctic mid-ocean spreading ridge.
AB  - In marine sediments archaea often constitute a considerable part of the microbial
      community, of which the Deep Sea Archaeal Group (DSAG) is one of the most
      predominant. Despite their high abundance no members from this archaeal group
      have so far been characterized and thus their metabolism is unknown. Here we show
      that the relative abundance of DSAG marker genes can be correlated with
      geochemical parameters, allowing prediction of both the potential electron donors
      and acceptors of these organisms. We estimated the abundance of 16S rRNA genes
      from Archaea, Bacteria, and DSAG in 52 sediment horizons from two cores collected
      at the slow-spreading Arctic Mid-Ocean Ridge, using qPCR. The results indicate
      that members of the DSAG make up the entire archaeal population in certain
      horizons and constitute up to ~50% of the total microbial community. The
      quantitative data were correlated to 30 different geophysical and geochemical
      parameters obtained from the same sediment horizons. We observed a significant
      correlation between the relative abundance of DSAG 16S rRNA genes and the content
      of organic carbon (p < 0.0001). Further, significant co-variation with iron
      oxide, and dissolved iron and manganese (all p < 0.0000), indicated a direct or
      indirect link to iron and manganese cycling. Neither of these parameters
      correlated with the relative abundance of archaeal or bacterial 16S rRNA genes,
      nor did any other major electron donor or acceptor measured. Phylogenetic
      analysis of DSAG 16S rRNA gene sequences reveals three monophyletic lineages with
      no apparent habitat-specific distribution. In this study we support the
      hypothesis that members of the DSAG are tightly linked to the content of organic
      carbon and directly or indirectly involved in the cycling of iron and/or
      manganese compounds. Further, we provide a molecular tool to assess their
      abundance in environmental samples and enrichment cultures. 

PMID- 24109476
TI  - Traumatic brain injury - modeling neuropsychiatric symptoms in rodents.
AB  - Each year in the US, ~1.5 million people sustain a traumatic brain injury (TBI).
      Victims of TBI can suffer from chronic post-TBI symptoms, such as sensory and
      motor deficits, cognitive impairments including problems with memory, learning,
      and attention, and neuropsychiatric symptoms such as depression, anxiety,
      irritability, aggression, and suicidal rumination. Although partially associated
      with the site and severity of injury, the biological mechanisms associated with
      many of these symptoms - and why some patients experience differing assortments
      of persistent maladies - are largely unknown. The use of animal models is a
      promising strategy for elucidation of the mechanisms of impairment and treatment,
      and learning, memory, sensory, and motor tests have widespread utility in rodent
      models of TBI and psychopharmacology. Comparatively, behavioral tests for the
      evaluation of neuropsychiatric symptomatology are rarely employed in animal
      models of TBI and, as determined in this review, the results have been
      inconsistent. Animal behavioral studies contribute to the understanding of the
      biological mechanisms by which TBI is associated with neurobehavioral symptoms
      and offer a powerful means for pre-clinical treatment validation. Therefore,
      further exploration of the utility of animal behavioral tests for the study of
      injury mechanisms and therapeutic strategies for the alleviation of emotional
      symptoms are relevant and essential. 

PMID- 24109478
TI  - Design of a large-scale femtoliter droplet array for single-cell analysis of drug
      tolerant and drug-resistant bacteria.
AB  - Single-cell analysis is a powerful method to assess the heterogeneity among
      individual cells, enabling the identification of very rare cells with properties
      that differ from those of the majority. In this Methods Article, we describe the
      use of a large-scale femtoliter droplet array to enclose, isolate, and analyze
      individual bacterial cells. As a first example, we describe the single-cell
      detection of drug-tolerant persisters of Pseudomonas aeruginosa treated with the
      antibiotic carbenicillin. As a second example, this method was applied to the
      single-cell evaluation of drug efflux activity, which causes acquired antibiotic
      resistance of bacteria. The activity of the MexAB-OprM multidrug efflux pump
      system from Pseudomonas aeruginosa was expressed in Escherichia coli and the
      effect of an inhibitor D13-9001 were assessed at the single cell level. 

PMID- 24109479
TI  - Multifaceted Impact of Host C-C Chemokine CCL2 in the Immuno-Pathogenesis of HIV
      1/M. tuberculosis Co-Infection.
AB  - Active tuberculosis remains the leading cause of death among the HIV-1
      seropositive individuals. Although significant success has been achieved in
      bringing down the number of HIV/AIDS-related mortality and morbidity following
      implementation of highly active anti-retroviral therapy (HAART). Yet, co
      infection of Mycobacterium tuberculosis (Mtb) has posed severe clinical and
      preventive challenges in our efforts to eradicate the virus from the body. Both
      HIV-1 and Mtb commonly infect macrophages and trigger production of host
      inflammatory mediators that subsequently regulate the immune response and disease
      pathogenesis. These inflammatory mediators can impose beneficial or detrimental
      effects on each pathogen and eventually on host. Among these, inflammatory C-C
      chemokines play a central role in HIV-1 and Mtb pathogenesis. However, their role
      in lung-specific mechanisms of HIV-1 and Mtb interaction are poorly understood.
      In this review we highlight current view on the role of C-C chemokines, more
      precisely CCL2, on HIV-1: Mtb interaction, potential mechanisms of action and
      adverse clinical consequences in a setting HIV-1/Mtb co-infection. Targeting
      common chemokine regulators of HIV-1/Mtb pathogenesis can be an attractive and
      potential anti-inflammatory intervention in HIV/AIDS-related comorbidities. 

PMID- 24109480
TI  - Human APECED; a Sick Thymus Syndrome?
AB  - Loss-of-function mutations in the Autoimmune Regulator (AIRE) gene cause a rare
      inherited form of autoimmune disease, autoimmune polyendocrinopathy-candidiasis
      ectodermal dystrophy, also known as autoimmune polyglandular syndrome type 1. The
      patients suffer from multiple endocrine deficiencies, the most common
      manifestations being hypoparathyroidism, Addison's disease, hypogonadism, and
      secondary amenorrhea, usually accompanied by typical autoantibodies against the
      target tissues. Chronic mucocutaneous candidiasis is also a prominent part of the
      disease. The highest expression of AIRE is found in medullary thymic epithelial
      cells (mTECs). Murine studies suggest that it promotes ectopic transcription of
      self antigens in mTECs and is thus important for negative selection. However,
      failed negative selection alone is not enough to explain key findings in human
      patients, necessitating the search for alternative or additional pathogenetic
      mechanisms. A striking feature of the human AIRE-deficient phenotype is that all
      patients develop high titers of neutralizing autoantibodies against type I
      interferons, which have been shown to downregulate the expression of interferon
      controlled genes. These autoantibodies often precede clinical symptoms and other
      autoantibodies, suggesting that they are a reflection of the pathogenetic
      process. Other cytokines are targeted as well, notably those produced by Th17
      cells; these autoantibodies have been linked to the defect in anti-candida
      defenses. A defect in regulatory T cells has also been reported in several
      studies and seems to affect already the recent thymic emigrant population. Taken
      together, these findings in human patients point to a widespread disruption of T
      cell development and regulation, which is likely to have its origins in an
      abnormal thymic milieu. The absence of functional AIRE in peripheral lymphoid
      tissues may also contribute to the pathogenesis of the disease. 

PMID- 24109481
TI  - The effect of age on thymic function.
AB  - Age-related regression of the thymus is associated with a decline in naive T cell
      output. This is thought to contribute to the reduction in T cell diversity seen
      in older individuals and linked with increased susceptibility to infection,
      autoimmune disease, and cancer. Thymic involution is one of the most dramatic and
      ubiquitous changes seen in the aging immune system, but the mechanisms which
      underlying this process are poorly understood. However, a picture is emerging,
      implicating the involvement of both extrinsic and intrinsic factors. In this
      review we assess the role of the thymic microenvironment as a potential target
      that regulates thymic involution, question whether thymocyte development in the
      aged thymus is functionally impaired, and explore the kinetics of thymic
      involution. 

PMID- 24109482
TI  - Comparative Genomic and Sequence Analysis Provides Insight into the Molecular
      Functionality of NOD1 and NOD2.
AB  - Amino acids with functional or key structural roles display higher degrees of
      conservation through evolution. The comparative analysis of protein sequences
      from multiple species and/or between homologous proteins can be highly
      informative in the identification of key structural and functional residues.
      Residues which in turn provide insight into the molecular mechanisms of protein
      function. We have explored the genomic and amino acid conservation of the
      prototypic innate immune genes NOD1 and NOD2. NOD1 orthologs were found in all
      vertebrate species analyzed, whilst NOD2 was absent from the genomes of avian,
      reptilian and amphibian species. Evolutionary trace analysis was used to identify
      highly conserved regions of NOD1 and NOD2 across multiple species. Consistent
      with the known functions of NOD1 and NOD2 highly conserved patches were
      identified that matched the Walker A and B motifs and provided interaction
      surfaces for the adaptor protein RIP2. Other patches of high conservation reflect
      key structural functions as predicted by homology models. In addition, the
      pattern of residue conservation within the leucine-rich repeat (LRR) region of
      NOD1 and NOD2 is indicative of a conserved mechanism of ligand recognition
      involving the concave surface of the LRRs. 

PMID- 24109484
TI  - The modulation of the cell-cycle: a sentinel to alert the NK cells of dangers.
AB  - Natural killer (NK) cells are an essential component of innate immunity that
      provides a rapid response to detect stressed, infected, or transformed target
      cells. This system is controlled by a balance of inhibitory and activating
      signals transmitted by a myriad of receptors and their specific ligands.
      Inhibitory receptors mainly recognize self-MHC class-I molecules, whereas
      activating receptors, such as natural cytotoxic receptors, NKG2D, and DNAM-1,
      interact with self-proteins, normally not expressed on the cell surface of
      healthy cells, but up-regulated by cellular stress or infections and are
      frequently expressed on tumor cells. In these circumstances, regulatory controls
      ensure that specific ligands are induced mainly in diseased cells and not in
      normal cells. Each ligand seems to exhibit some distinct specializations
      providing broad "coverage" for numerous stresses associated with various
      diseases. Deregulated cell proliferation is a hallmark of these abnormal
      situations, and may serve as a sentinel for the elimination of the targets by NK
      cells. The purpose of this review is to discuss recent implications of cell-cycle
      to create a warning control system that relays various danger signals via
      specific ligands to the NK receptor system. 

PMID- 24109483
TI  - Nucleic Acid sensors and type I interferon production in systemic lupus
      erythematosus.
AB  - The characteristic serologic feature of systemic lupus erythematosus (SLE) is
      autoantibodies against one's own nucleic acid or nucleic acid-binding proteins -
      DNA and RNA-binding nuclear proteins. Circulating autoantibodies can deposit in
      the tissue, causing inflammation and production of cytokines such as type 1
      interferon (IFN). Investigations in human patients and animal models have
      implicated environmental as well as genetic factors in the biology of the SLE
      autoimmune response. Viral/Bacterial nucleic acid is a potent stimulant of innate
      immunity by both toll-like receptor (TLR) and non-TLR signaling cascades.
      Additionally, foreign DNA may act as an immunogen to drive an antigen-specific
      antibody response. Self nucleic acid is normally restricted to the nucleus or the
      mitochondria, away from the DNA/RNA sensors, and mechanisms exist to
      differentiate between foreign and self nucleic acid. In normal immunity, a
      diverse range of DNA and RNA sensors in different cell types form a dynamic and
      integrated molecular network to prevent viral infection. In SLE, pathologic
      activation of these sensors occurs via immune complexes consisting of
      autoantibodies bound to DNA or to nucleic acid-protein complexes. In this review,
      we will discuss recent studies outlining how mismanaged nucleic acid sensing
      networks promote autoimmunity and result in the over-production of type I IFN.
      This information is critical for improving therapeutic strategies for SLE
      disease. 

PMID- 24109485
TI  - A CRISPR CASe for high-throughput silencing.
AB  - Manipulation of gene expression on a genome-wide level is one of the most
      important systematic tools in the post-genome era. Such manipulations have
      largely been enabled by expression cloning approaches using sequence-verified
      cDNA libraries, large-scale RNA interference libraries (shRNA or siRNA) and zinc
      finger nuclease technologies. More recently, the CRISPR (clustered regularly
      interspaced short palindromic repeats) and CRISPR-associated (Cas)9-mediated gene
      editing technology has been described that holds great promise for future use of
      this technology in genomic manipulation. It was suggested that the CRISPR system
      has the potential to be used in high-throughput, large-scale loss of function
      screening. Here we discuss some of the challenges in engineering of CRISPR/Cas
      genomic libraries and some of the aspects that need to be addressed in order to
      use this technology on a high-throughput scale. 

PMID- 24109486
TI  - The effects of transcription factor competition on gene regulation.
AB  - Transcription factor (TF) molecules translocate by facilitated diffusion (a
      combination of 3D diffusion around and 1D random walk on the DNA). Despite the
      attention this mechanism received in the last 40 years, only a few studies
      investigated the influence of the cellular environment on the facilitated
      diffusion mechanism and, in particular, the influence of "other" DNA binding
      proteins competing with the TF molecules for DNA space. Molecular crowding on the
      DNA is likely to influence the association rate of TFs to their target site and
      the steady state occupancy of those sites, but it is still not clear how it
      influences the search in a genome-wide context, when the model includes
      biologically relevant parameters (such as: TF abundance, TF affinity for DNA and
      TF dynamics on the DNA). We performed stochastic simulations of TFs performing
      the facilitated diffusion mechanism, and considered various abundances of cognate
      and non-cognate TFs. We show that, for both obstacles that move on the DNA and
      obstacles that are fixed on the DNA, changes in search time are not statistically
      significant in case of biologically relevant crowding levels on the DNA. In the
      case of non-cognate proteins that slide on the DNA, molecular crowding on the DNA
      always leads to statistically significant lower levels of occupancy, which may
      confer a general mechanism to control gene activity levels globally. When the
      "other" molecules are immobile on the DNA, we found a completely different
      behavior, namely: the occupancy of the target site is always increased by higher
      molecular crowding on the DNA. Finally, we show that crowding on the DNA may
      increase transcriptional noise through increased variability of the occupancy
      time of the target sites. 

PMID- 24109487
TI  - Correlation between PPAR Gene Polymorphisms and Primary Nephrotic Syndrome in
      Children.
AB  - Pediatric primary nephrotic syndrome (PNS) is a chronic disease promoted by
      metabolic and immune dysfunctions. Peroxisome proliferator-activated receptor
      (PPAR) polymorphisms have been associated with a variety of metabolic and kidney
      disorders. We therefore hypothesized that PPAR polymorphisms might be involved in
      the pathophysiology of PNS. We compared the distributions of the PPAR-gamma
      Pro12Ala and Val290Met, PPAR-gamma coactivator-alpha (PGC-1alpha) Gly482Ser, and
      PPAR-alpha Leu162Val single nucleotide polymorphisms (SNPs) between children with
      PNS and normal controls and analyzed their correlations with clinical and
      metabolic indicators and steroid responsiveness. There were no significant
      differences in distributions of any of the polymorphisms between PNS cases and
      controls. However, PNS patients with the PPAR-gamma (Pro12Ala) PP genotype had
      significantly higher fasting serum insulin, IgA, and HOMA-IR levels and lower
      insulin sensitivity than did patients with PA and AA genotypes. Additionally, the
      PGC-1alpha (Gly482Ser) A allele was associated with lower CD8+ T-cell counts and
      higher triglyceride and complement C3 levels compared with the G allele. No
      polymorphisms were related to hormone sensitivity. These results suggest that the
      PPAR-gamma (Pro12Ala) and PGC-1alpha (Gly482Ser) SNPs may influence insulin and
      triglyceride metabolism in children with PNS and may thus be relevant to the
      prognosis of this chronic condition. 

PMID- 24109488
TI  - Effects of bFGF on the Modulation of Apoptosis in Gingival Fibroblasts with
      Different Host Ages.
AB  - The purpose of this study was to investigate the effects of basic fibroblast
      growth factor (bFGF) treatment on the proliferation and apoptosis of cultured
      gingival fibroblasts (GFs). Human GFs were isolated from the palatal gingival
      tissues of 16 healthy volunteers ranging in the age from 9 to 35 years old.
      Cultured GFs were subjected to the analyses for cell proliferation by ELISA
      assay, gene expression by RT-PCR analysis, and apoptosis potency by caspase-3
      assay. The cell proliferation activity and gene expression of type-I collagen and
      caspase-3 activity were enhanced significantly by the treatment with bFGF in
      cultured GFs. Furthermore, the activity of caspase-3 in cultured GFs from young
      subjects was significantly higher than that in GFs from adults. It is shown that
      bFGF significantly enhances the gene expression of type-I collagen in cultured
      fibroblasts from human gingival tissues. It also demonstrated that bFGF modulates
      the apoptosis of periodontal fibroblasts, and the effect is higher in young
      subjects, indicating a significant role of bFGF in the prevention of scar
      formation during wound healing. 

PMID- 24109489
TI  - Myeloid sarcoma developing in prexisting hydroxyurea-induced leg ulcer in a
      polycythemia vera patient.
AB  - Myeloid sarcoma (MS) is an extramedullary tumour consisting of myeloblasts or
      immature myeloid cells located in an extramedullary site. It may occur at
      presentation of AML, at relapse, or prior to the onset of frank leukemia. We
      report a rare case of MS developing in prexisting Hydroxyurea-induced leg Ulcer
      in a 70-year-old woman. 

PMID- 24109490
TI  - Loranthus micranthus Linn.: Biological Activities and Phytochemistry.
AB  - Loranthus micranthus Linn. is a medicinal plant from the Loranthaceae family
      commonly known as an eastern Nigeria species of the African mistletoe and is
      widely used in folkloric medicine to cure various ailments and diseases. It is
      semiparasitic plant because of growing on various host trees and shrubs and
      absorbing mineral nutrition and water from respective host. Hence, the
      phytochemicals and biological activities of L. micranthus demonstrated strong
      host and harvesting period dependency. The leaves have been proved to possess
      immunomodulatory, antidiabetic, antimicrobial, antihypertensive, antioxidant,
      antidiarrhoeal, and hypolipidemic activities. This review summarizes the
      information and findings concerning the current knowledge on the biological
      activities, pharmacological properties, toxicity, and chemical constituents of
      Loranthus micranthus. 

PMID- 24109492
TI  - Antimicrobial activity of lippia species from the brazilian semiarid region
      traditionally used as antiseptic and anti-infective agents.
AB  - Lippia origanoides Kunth, Lippia alnifolia Schauer, and Lippia thymoides Martius
      and Schauer are shrubs used in the traditional Brazilian medicine as antiseptics,
      as well as in the treatment of infectious diseases. This study was designed to
      investigate the antibacterial and antifungal activities of the methanolic
      extracts of these species, as new potential sources of antimicrobial drugs. The
      antimicrobial activity of methanolic extracts was investigated against resistant
      yeasts and bacteria by agar disk diffusion. Then, the MIC determination of the
      most active species and its fractions in hexane, dichloromethane, ethyl acetate,
      and water was performed. By the agar diffusion assay, all species were active
      against at least two microorganisms, giving evidence to support their use in the
      popular medicine. L. origanoides leaves exhibited the widest antimicrobial
      action, inhibiting the growth of two Gram-positive bacteria and two yeasts; this
      activity was also confirmed by the MIC evaluation. The fractionation of L.
      origanoides crude extracts improved the activity in spectrum and intensity. The
      results obtained in this study indicate that L. origanoides may be a promising
      alternative in the treatment of bacterial and fungal infections and in the
      seeking of new antimicrobial drugs. 

PMID- 24109491
TI  - A current update on the rule of alternative and complementary medicine in the
      treatment of liver diseases.
AB  - There is a vast body of knowledge which is ever-increasing about the treatment of
      liver disease with alternative and complementary medicine for which hundreds of
      thousands of literatures have been documented. Liver disease is a general term.
      This term covers all the potential problems that cause the liver to fail to
      perform its specified operations. Liver disease has a variety of presentations
      and causes a great public health problem worldwide which threatens the wellness
      of billions of people. Incidences of many types of liver disease are currently
      rising. Although there is still a debate about the entity of alternative and
      complementary medicine, it is now widely used and it is improving. And it covers
      the shortages and compensates for the weaknesses of conventional methods in the
      treatment of liver diseases. Alternative and complementary medicine for liver
      diseases provides benefits by regulating immunity, controlling disease
      progression, improving quality of life, and prolonging survival. This paper
      reviews the increasing interest and growing research into alternative and
      complementary medicine for liver diseases, with a look at the rough
      classification, principle of management, evidence-based applications, and issues
      for prescription and perspectives. 

PMID- 24109493
TI  - Developing and testing the effectiveness of a novel health qigong for frail
      elders in Hong Kong: a preliminary study.
AB  - Eight-Section Brocades and Yijin Jing consist of some routine movements that are
      too difficult for frail elders. A novel health qigong protocol was developed and
      its effectiveness for frail elders was examined using a randomized clinical trial
      (RCT). An expert panel performed functional anatomy analysis and safety field
      test prior to the RCT. The experimental group (n = 61, 83 +/- 6 yr) was given a
      12-week qigong exercise program, while the comparison group (n = 55, 84 +/- 6 yr)
      participated in a newspaper reading program with the same duration and frequency.
      Pre-, mid-, post-, and follow-up assessments were conducted. At 12 weeks, the
      qigong group had significant improvements in thinking operations (F = 4.05, P =
      .02) and significant reduction of resting heart rate (F = 3.14, P = .045) as
      compared to the newspaper reading group. A trend of improvements in grip strength
      and a decreasing trend of depression levels were observed among the qigong group.
      Significant perceived improvements in physical health (F = 13.01, P = .001),
      activities of daily living (F = 5.32, P = .03), and overall health status (F =
      15.26, P = .0001) were found. There are improvements in some aspects of
      psychosocial, cognitive, physical, and physiological domains. Clinical
      applications and possibilities for further research are discussed. 

PMID- 24109494
TI  - Fluids, rivers, and vessels: metaphors and body concepts in Mesopotamian
      gynaecological texts.
AB  - This paper discusses the peculiar disease condition of "locked fluids" found in a
      number of gynaecological texts from 2nd and 1st millennium BCE Mesopotamia. To
      venture an interpretation of the underlying disease concept, the condition of
      "locked fluids" is first examined in the context of related and contrasting
      symptoms and female health problems connected to body fluids within the
      gynaecological corpus. The second part of this article turns to the physiological
      concepts of the (female) body linked to the disease condition of "locked fluids".
      The author highlights metaphors and comparisons with objects from daily life and
      the natural environment, which can be found in medical incantations and
      therapeutic rituals used to combat gynaecological disorders, as a key to
      indigenous concepts of physiology. The use of the same metaphors in connection
      with intestinal disorders points to an intuitive understanding of different
      processes within the body on the basis of comparisons and equations stemming from
      daily-life experiences. The last section presents similar notions to the
      Mesopotamian disease concept of "locked fluids", which are contained in
      gynaecological treatises of other cultures and times.

PMID- 24109496
TI  - Coronary-cameral fistulas in adults (first of two parts).
AB  - This is a case series and review of the literature adding 11 new cases. Coronary
      cameral fistulas (CCFs) are infrequent anomalies which are in general co
      incidentally found during diagnostic coronary angiography (CAG). To delineate the
      characteristics of congenital and acquired CCFs in adults, we performed a PubMed
      search for papers dealing with congenital or acquired CCFs in adults.
      Publications on coronary-vascular fistulas or paediatric subjects were not
      included. From the world literature, a total of 243 adult patients were
      identified who had congenital (65%) or acquired (35%) CCFs. In this review, which
      is part one of a two-part series on CCFs, we describe and discuss the congenital
      fistulas, give an overview on the published literature and report details of our
      own series of 11 patients with MMFs and solitary macro CCFs. Of the congenital
      group, 85% were small or large solitary macro CCFs (cut-off 1.5 mm) and 15% were
      coronary artery-ventricular multiple micro-fistulas (MMFs). Apical hypertrophic
      cardiomyopathy was reported in some of the reviewed subjects with MMFs (3/24 =
      13%) but not was seen in our own series. Conservative medical management was
      generally the treatment of choice in congenital MMFs; prophylactic implantable
      cardioverter defibrillators (ICD) were implanted in 2/24 (8%) of subjects,
      especially when extensive micro-fistulisations were involved. None of the
      patients of our own series required an ICD, as the MMFs were of limited size.
      Congenital or acquired CCFs in adults are infrequent anomalies having a wide
      spectrum of clinical presentation may varies from asymptomatic to severely
      devastating states requiring different treatment modalities. 

PMID- 24109495
TI  - Hyponatremia in patients with heart failure.
AB  - The present review analyses the mechanisms relating heart failure and
      hyponatremia, describes the association of hyponatremia with the progress of
      disease and morbidity/mortality in heart failure patients and presents treatment
      options focusing on the role of arginine vasopressin (AVP)-receptor antagonists.
      Hyponatremia is the most common electrolyte disorder in the clinical setting and
      in hospitalized patients. Patients with hyponatremia may have neurologic symptoms
      since low sodium concentration produces brain edema, but the rapid correction of
      hyponatremia is also associated with major neurologic complications. Patients
      with heart failure often develop hyponatremia owing to the activation of many
      neurohormonal systems leading to decrease of sodium levels. A large number of
      clinical studies have associated hyponatremia with increased morbidity and
      mortality in patients hospitalized for heart failure or outpatients with chronic
      heart failure. Treatment options for hyponatremia in heart failure, such as water
      restriction or the use of hypertonic saline with loop diuretics, have limited
      efficacy. AVP-receptor antagonists increase sodium levels effectively and their
      use seems promising in patients with hyponatremia. However, the effects of AVP
      receptor antagonists on hard outcomes in patients with heart failure and
      hyponatremia have not been thoroughly examined. 

PMID- 24109498
TI  - Subcutaneous implantable defibrillator: State-of-the art 2013.
AB  - The subcutaneous implantable cardioverter-defibrillator (S-ICD) has recently been
      approved for commercial use in Europe, New Zealand and the United States. It is
      comprised of a pulse generator, placed subcutaneously in a left lateral position,
      and a parasternal subcutaneous lead-electrode with two sensing electrodes
      separated by a shocking coil. Being an entirely subcutaneous system it avoids
      important periprocedural and long-term complications associated with transvenous
      implantable cardioverter-defibrillator (TV-ICD) systems as well as the need for
      fluoroscopy during implant surgery. Suitable candidates include pediatric
      patients with congenital heart disease that limits intracavitary lead placements,
      those with obstructed venous access, chronic indwelling catheters or high
      infection risk, as well as young patients with electrical heart disease (e.g.,
      Brugada Syndrome, long QT syndrome, and hypertrophic cardiomyopathy).
      Nevertheless, given the absence of intracavitary leads, the S-ICD is unable to
      offer pacing (apart from short-term post-shock pacing). It is therefore not
      suitable in patients with an indication for antibradycardia pacing or cardiac
      resynchronization therapy, or with a history of repetitive monomorphic
      ventricular tachycardia that would benefit from antitachycardia pacing. Current
      data from initial clinical studies and post-commercialization "real-life" case
      series, including over 700 patients, have so far been promising and shown that
      the S-ICD successfully converts induced and spontaneous ventricular
      tachycardia/ventricular fibrillation episodes with associated complication and
      inappropriate shock rates similar to that of TV-ICDs. Furthermore, by using far
      field electrograms better tachyarrhythmia discrimination when compared to TV-ICDs
      has been reported. Future results from ongoing clinical studies will determine
      the S-ICD system's long-term performance, and better define suitable patient
      profiles. 

PMID- 24109497
TI  - Relationship between vitamin D deficiency and cardiovascular disease.
AB  - Epidemiological studies have found that low 25-hydroxyvitamin D levels may be
      associated with coronary risk factors and adverse cardiovascular outcomes.
      Additionally, vitamin D deficiency causes an increase in parathyroid hormone,
      which increases insulin resistance and is associated with diabetes, hypertension,
      inflammation, and increased cardiovascular risk. In this review, we analyze the
      association between vitamin D supplementation and the reduction in cardiovascular
      disease. The role of vitamin D deficiency in cardiovascular morbidity and
      mortality is still controversial, and larger scale, randomized placebo controlled
      trials are needed to investigate whether oral vitamin D supplementation can
      reduce cardiovascular risk. Given the low cost, safety, and demonstrated benefit
      of higher 25-hydroxyvitamin D levels, vitamin D supplementation should become a
      public health priority for combating common and costly chronic cardiovascular
      diseases. 

PMID- 24109499
TI  - Cardiac resynchronization therapy in acute pulmonary edema: A case report.
AB  - We are reporting a case of 71-year old lady with a dual chamber demand pacemaker,
      who developed acute pulmonary edema due to an acute left ventricular (LV)
      dysfunction and worsening in mitral valve regurgitation after atrioventricular
      nodal ablation for uncontrolled atrial fibrillation. This was attributed to right
      ventricular apical pacing leading to LV dyssynchronization. Patient dramatically
      improved within 12-24 h after upgrading her single chamber pacemaker to
      biventricular pacing. Our case demonstrates that biventricular pacing can be an
      effective modality of treatment of acute congestive heart failure. In particular,
      it can be used when it is secondary to LV dysfunction and severe mitral
      regurgitation attributed to significant dyssynchrony created by right ventricular
      pacing in patients with atrioventricular nodal ablation for chronic atrial
      fibrillation. 

PMID- 24109500
TI  - Exercise-induced left bundle branch block: an infrequent phenomenon: Report of
      two cases.
AB  - Exercise-induced left bundle branch block (EI-LBBB) is infrequent phenomenon. We
      present two patients with angina pectoris who developed EI-LBBB during exercise
      tolerance test. The first patient with typical angina pectoris had significant
      obstructive coronary artery disease (CAD) requiring percutaneous coronary
      intervention of multiple lesions including placement of drug eluting stents. The
      second patient had atypical chest pain without signs of CAD at all. EI-LBBB
      occurred at a heart rate of 80 bpm and 141 bpm in the first and second patient,
      respectively. EI-LBBB remained visible through the test till the recovery period
      in the first patient at a heart rate of 83 bpm and disappeared at 96 bpm in the
      second patient. Both patients with this infrequent phenomenon are discussed and
      the literature is reviewed. 

PMID- 24109501
TI  - Complete regression of myocardial involvement associated with lymphoma following
      chemotherapy.
AB  - Cardiac involvement as an initial presentation of malignant lymphoma is a rare
      occurrence. We describe the case of a 26 year old man who had initially been
      diagnosed with myocardial infiltration on an echocardiogram, presenting with a
      testicular mass and unilateral peripheral facial paralysis. On admission,
      electrocardiograms (ECG) revealed negative T-waves in all leads and ST-segment
      elevation in the inferior leads. On two-dimensional echocardiography, there was
      infiltration of the pericardium with mild effusion, infiltrative thickening of
      the aortic walls, both atria and the interatrial septum and a mildly depressed
      systolic function of both ventricles. An axillary biopsy was performed and
      reported as a T-cell lymphoblastic lymphoma (T-LBL). Following the diagnosis and
      staging, chemotherapy was started. Twenty-two days after finishing the first
      cycle of chemotherapy, the ECG showed regression of T-wave changes in all leads
      and normalization of the ST-segment elevation in the inferior leads. A follow-up
      Two-dimensional echocardiography confirmed regression of the myocardial
      infiltration. This case report illustrates a lymphoma presenting with testicular
      mass, unilateral peripheral facial paralysis and myocardial involvement, and
      demonstrates that regression of infiltration can be achieved by intensive
      chemotherapy treatment. To our knowledge, there are no reported cases of T-LBL
      presenting as a testicular mass and unilateral peripheral facial paralysis, with
      complete regression of myocardial involvement. 

PMID- 24109502
TI  - Endovascular technique using a snare and suture for retrieving a migrated
      peripherally inserted central catheter in the left pulmonary artery.
AB  - We report a successful endovascular technique using a snare with a suture for
      retrieving a migrated broken peripherally inserted central catheter (PICC) in a
      chemotherapy patient. A 62-year-old male received monthly chemotherapy through a
      central venous port implanted into his right subclavian area. The patient
      completed chemotherapy without complications 1 mo ago; however, he experienced
      pain in the right subclavian area during his last chemotherapy session. Computed
      tomography on that day showed migration of a broken PICC in his left pulmonary
      artery, for which the patient was admitted to our hospital. We attempted to
      retrieve the ectopic PICC through the right jugular vein using a gooseneck snare,
      but were unsuccessful because the catheter was lodged in the pulmonary artery
      wall. Therefore, a second attempt was made through the right femoral vein using a
      snare with triple loops, but we could not grasp the migrated PICC. Finally, a
      string was tied to the top of the snare, allowing us to curve the snare toward
      the pulmonary artery by pulling the string. Finally, the catheter body was
      grasped and retrieved. The endovascular suture technique is occasionally
      extremely useful and should be considered by interventional cardiologists for
      retrieving migrated catheters. 

PMID- 24109503
TI  - Persistent left superior vena cava and pacemaker implantation.
AB  - Our study group read with interest the paper from Vijayvergiya et al describing
      the implantation of an implantable cardioverter-defibrillator lead in the
      presence of the persistence of the left superior vena cava. The issue of the
      identification a persistent left superior vena cava is of paramount importance in
      interventional cardiology, being the most common venous anomaly of the thoracic
      distribution, and because it may create some problem to any physician while
      performing a pacemaker lead implantation. In our letter we underscore the
      specific issues related to pacemaker implantation while encountering a persistent
      left superior vena cava (and maybe the absence of the right vena cava) and the
      workup that should be performed to obtain the preoperative diagnosis of the
      venous anomaly. More specifically, we consider avoiding any kind of defibrillator
      lead implantation through the coronary sinus for safety issues, and underscore
      the straightforward transthoracic ultrasound approach to identify the left
      superior vena cava. 

PMID- 24109504
TI  - Spatial hearing and hearing aids.

PMID- 24109505
TI  - Umbilical cord blood stem cells replenish mesenchymal cell lineages.

PMID- 24109506
TI  - Mouse phenotyping consortium identifies novel osteoporosis genes.

PMID- 24109507
TI  - Losing weight in old age is a major risk factor for hyperkyphosis.

PMID- 24109508
TI  - Inhibiting PHOSPHO1 reduces calcification in smooth muscle cells.

PMID- 24109509
TI  - Role for VEGF in osteoporosis development?

PMID- 24109510
TI  - Incidence and variants of posterior arch defects of the atlas vertebra.
AB  - In order to describe the incidence and existing variants of congenital anomalies
      of the atlas vertebrae in a Caucasian population, we examined 1069 CT scans of
      the upper cervical spine. We found 41 cases with altered atlas vertebrae,
      representing 3.8% of all analyzed patients. With 83% of all found anomalies, the
      predominant type is characterized by a small dorsal cleft (3.2% of all patients).
      Rare varieties feature unilateral or bilateral dorsal arch defects, combined
      anterior and posterior clefts (0.2% of all patients) or total erratic atlas
      vertebra malformation (0.1% of all patients). Atlas arch defects are found nearly
      4% at the time. Most anomalies affect the posterior arch, whereas the anterior
      arch or both are rarely affected. Totally irregular C1 vertebrae are extremely
      infrequent. 

PMID- 24109511
TI  - Merkel cell carcinoma of the head and neck: challenges in diagnosis and therapy.

PMID- 24109512
TI  - The effect of polymer content on the non-newtonian behavior of acetaminophen
      suspension.
AB  - Acetaminophen is used as an analgesic and antipyretic agent. The aim of the study
      was evaluation of the effect of different polymers on rheological behavior of
      acetaminophen suspension. In order to achieve controlled flocculation, sodium
      chloride was added. Then structural vehicles such as carboxymethyl cellulose
      (CMC), polyvinyl pyrrolidone (PVP), tragacanth, and magnesium aluminum silicate
      (Veegum) were evaluated individually and in combination. Physical stability
      parameters such as sedimentation volume (F), redispersibility (n), and growth of
      crystals of the suspensions were determined. Also, the rheological properties of
      formulations were studied. The results of this study showed that the combination
      of suspending agents had the most physical stability and pseudoplastic behavior
      with some degree of thixotropy. Viscosity of suspensions was increased by adding
      NaCl 0.02%. Presence of PVP is necessary for improving rheological behavior of
      suspensions by NaCl. This may be related to the cross-linking between the
      carbonyl group in the PVP segment and Na(+) ions. 

PMID- 24109513
TI  - Proof of Principle for a Real-Time Pathogen Isolation Media Diagnostic: The Use
      of Laser-Induced Breakdown Spectroscopy to Discriminate Bacterial Pathogens and
      Antimicrobial-Resistant Staphylococcus aureus Strains Grown on Blood Agar.
AB  - Laser-Induced Breakdown Spectroscopy (LIBS) is a rapid, in situ, diagnostic
      technique in which light emissions from a laser plasma formed on the sample are
      used for analysis allowing automated analysis results to be available in seconds
      to minutes. This speed of analysis coupled with little or no sample preparation
      makes LIBS an attractive detection tool. In this study, it is demonstrated that
      LIBS can be utilized to discriminate both the bacterial species and strains of
      bacterial colonies grown on blood agar. A discrimination algorithm was created
      based on multivariate regression analysis of spectral data. The algorithm was
      deployed on a simulated LIBS instrument system to demonstrate discrimination
      capability using 6 species. Genetically altered Staphylococcus aureus strains
      grown on BA, including isogenic sets that differed only by the acquisition of
      mutations that increase fusidic acid or vancomycin resistance, were also
      discriminated. The algorithm successfully identified all thirteen cultures used
      in this study in a time period of 2 minutes. This work provides proof of
      principle for a LIBS instrumentation system that could be developed for the rapid
      discrimination of bacterial species and strains demonstrating relatively minor
      genomic alterations using data collected directly from pathogen isolation media. 

PMID- 24109514
TI  - Implication for bone marrow derived stem cells in hepatocyte regeneration after
      orthotopic liver transplantation.
AB  - The liver has the outstanding ability to regenerate itself and restore
      parenchymal tissue after injury. The most common cell source in liver
      growth/regeneration is replication of preexisting hepatocytes although liver
      progenitor cells have been postulated to participate in liver regeneration in
      cases of massive injury. Bone marrow derived hematopoietic stem cells (BM-HSC)
      have the formal capacity to act as a source for hepatic regeneration under
      special circumstances; however, the impact of this process in liver tissue
      maintenance and regeneration remains controversial. Whether BM-HSC are involved
      in liver regeneration or not would be of particular interest as the cells have
      been suggested to be an alternative donor source for the treatment of liver
      failure. Data from murine models of liver disease show that BM-HSC can repopulate
      liver tissue and restore liver function; however, data obtained from human liver
      transplantation show only little evidence for liver regeneration by this
      mechanism. The cell source for liver regeneration seems to depend on the nature
      of regeneration process and the extent of injury; however, the precise mechanisms
      still need to be resolved. Current data suggest, that in human orthotopic liver
      transplantation, liver regeneration by BM-HSC is a rather rare event and
      therefore not of clinical relevance. 

PMID- 24109515
TI  - Serum levels of asymmetric dimethylarginine, vascular endothelial growth factor,
      and nitric oxide metabolite levels in preeclampsia patients.
AB  - Background. Hypertensive disorder generally complicates 5-10 percent of all
      pregnancies. Angiogenic growth factors may be helpful for the diagnosis and
      prediction of preeclampsia. Therefore, in this study we attempted to determine
      the serum levels of asymmetric dimethylarginine (ADMA), vascular endothelial
      growth factor (VEGF), and nitric oxide (NO) metabolite (nitrite) in preeclampsia
      patients and compared the levels with those obtained from normal pregnant women.
      Methods. Ninety pregnant women (19-33 years old) in two groups of preeclampsia
      and normal were considered during 2012. The levels of ADMA, VEGF, and nitrite
      were measured in maternal serum samples using ELISA kits. Results. Significant
      increase of VEGF and nitrite levels was observed in preeclampsia patients when
      compared with other groups (P < 0.05). The serum level of ADMA demonstrated a
      similar increased trend in preeclampsia patients; however, the increase was not
      statistically significant (P = 0.08). Conclusion. The findings reveal that the
      elevation of serum levels of VEGF and nitrite and possibly ADMA may be involved
      in the pathogenesis of preeclampsia. 

PMID- 24109516
TI  - N-Terminal proBNP Levels and Tissue Doppler Echocardiography in Acute Rheumatic
      Carditis.
AB  - Background. Rheumatic heart disease (RHD) is a leading cause of heart failure in
      children and young adults worldwide. B-type natriuretic peptide (BNP) is a useful
      marker of critical pediatric heart disease, and its N-terminal peptide, NT
      proBNP, is elevated in congenital and acquired heart disease in children. Aim. To
      measure NT-proBNP levels as a marker of carditis in children with acute rheumatic
      carditis, as compared to children with quiescent RHD and healthy controls.
      Methods. 16 children with acute rheumatic carditis, 33 children with quiescent
      RHD, and a cohort of 30 healthy children were studied. Transthoracic
      echocardiography was performed to assess valve and cardiac function. Tissue
      Doppler echocardiography was performed for E/E' (ratio between mitral inflow E
      wave and lateral mitral annulus E' wave) and systolic strain. Results. NT-proBNP
      levels were significantly higher in children with acute rheumatic carditis and
      dropped with its resolution. Strain and E/E' values were comparable among the
      three groups. Conclusion. NT-proBNP is significantly elevated in children with
      acute rheumatic carditis in the acute stage compared to children with quiescent
      RHD and healthy subjects, in the presence of comparable echocardiographic indices
      of LV systolic and diastolic function. 

PMID- 24109517
TI  - Reasons for Nonattendance across the Hepatitis C Disease Course.
AB  - This descriptive qualitative study examined the patient, provider, and
      institutional factors contributing to nonattendance for hepatitis C (HCV) care
      throughout the disease course. Eighty-four patients and health and social care
      providers were interviewed. Thematic analysis of the data yielded 6 interrelated
      nonattendance themes: self-protection, determining the benefits, competing
      priorities, knowledge gaps, access to services, and restrictive policies. Factors
      within the themes varied with the disease course, type of provider/service, and
      patient context. Nonattendance could span months to years and most frequently
      began at diagnosis where providers either advised that followup was not necessary
      or did not recommend any followup. The way services were organized (low barrier
      access) and delivered (nonjudgmental approach) and higher HCV knowledge levels of
      patients and providers encouraged attendance. This is the first study to explore
      the reasons for nonattendance for HCV care throughout the disease course and
      validate them from multiple perspectives. There are missed opportunities for
      providers to encourage attendance throughout the disease course beginning at
      diagnosis. Interventions required include development of integrated health and
      social service delivery models; mechanisms to improve knowledge dissemination of
      the disease, its management, and treatment; and implementation of standardized
      followup protocols for liver disease monitoring in primary care. 

PMID- 24109518
TI  - Early versus Late Surgical Treatment for Neurogenic Thoracic Outlet Syndrome.
AB  - Objectives. To compare the outcome of early surgical intervention versus late
      surgical treatment in cases of neurogenic thoracic outlet syndrome (NTOS).
      Design. Prospective study. Settings. Secondary care (Al-Minia University
      Hospital, Egypt) from 2007 to 2010. Participants. Thirty-five patients of NTOS
      (25 women and 10 men, aged 20-52 years), were classified into 2 groups. First
      group (20 patients) was operated within 3 months of the onset and the second
      group (15 patients) was operated 6 months after physiotherapy. Interventions. All
      patients were operated via supraclavicular surgical approach. Outcomes Measures.
      Both groups were evaluated clinically and, neurophysiologically and answered the
      disabilities of the arm, shoulder, and hand (DASH) questionnaire preoperatively
      and 6 months after the surgery. Results. Paraesthesia, pain, and sensory nerve
      action potential (SNAP) of ulnar nerve were significantly improved in group one.
      Muscle weakness and denervation in electromyography EMG were less frequent in
      group one. The postoperative DASH score improved in both groups but it was less
      significant in group two (P < .001 in group 1 and P < .05 in group 2).
      Conclusions. Surgical treatment of NTOS improves functional disability and stop
      degeneration of the nerves. Early surgical treatment decreases the occurrence of
      muscle wasting and denervation of nerves compared to late surgery. 

PMID- 24109519
TI  - Dynamics of B-Cell Populations in CSF and Blood in Patients Treated with a
      Combination of Rituximab and Mitoxantrone.
AB  - Background. Mitoxantrone (MTX) and Rituximab (RTX) are successfully used for
      treatment of multiple sclerosis (MS) and can be combined to increase efficacy.
      Objective. We used MTX, RTX, and methylprednisolone in a single combined regiment
      and observed patients prospectively. Methods. We present results of observational
      pilot study of combined therapy of RTX and MTX in 28 patients with active MS.
      Therapeutic protocol consisted of two infusions within 14 days. First infusion
      was 1000 mg methylprednisolone (MP) IV, 1000 mg RTX IV, and 20 mg MTX IV. On day
      14, 1000 mg MP IV and 1000 mg RTX IV were given. Patients were followed
      prospectively from 12 to 48 months. Results and Conclusion. There were no
      relapses among all 28 patients during the observation period. B-cell depletion of
      CD19+ and CD19+/CD27+ memory B-cell subpopulation in both compartments was
      confirmed in all patients at 6 months. We found a more rapid reconstitution of B
      cells in the CSF than in the peripheral blood and longstanding depression of
      CD19+CD27+ memory B-cell. Conclusion. Effectiveness of combined regimen of RTX
      and MTX could be related to longstanding depletion of CD19+CD27+ memory B-cell
      subset. 

PMID- 24109520
TI  - Noneczematous contact dermatitis.
AB  - Irritant or allergic contact dermatitis usually presents as an eczematous
      process, clinically characterized by erythematoedematovesicous lesions with
      intense itching in the acute phase. Such manifestations become erythematous-scaly
      as the condition progresses to the subacute phase and papular-hyperkeratotic in
      the chronic phase. Not infrequently, however, contact dermatitis presents with
      noneczematous features. The reasons underlying this clinical polymorphism lie in
      the different noxae and contact modalities, as well as in the individual
      susceptibility and the various targeted cutaneous structures. The most
      represented forms of non-eczematous contact dermatitis include the erythema
      multiforme-like, the purpuric, the lichenoid, and the pigmented kinds. These
      clinical entities must obviously be discerned from the corresponding "pure"
      dermatitis, which are not associated with contact with exogenous agents. 

PMID- 24109521
TI  - Is There a Limitation of RECIST Criteria in Prediction of Pathological Response,
      in Head and Neck Cancers, to Postinduction Chemotherapy?
AB  - This study studied the coorelation between radiological response to induction
      chemotherapy and acheivement of pCR or near pCR. It was a retrospective analysis
      in which all patients who received NACT from 2008 till april 2012 were subjected
      to inclusion criteria. Coorelation analysis was performed between CR + PR and
      acheivement of pCR or near pCR. Twenty four patients were identified.The primary
      site of tumor was oral cavity in 19 patients (79.2%), maxilla in 2 patients
      (4.2%), laryngopharynx in 2 patients (4.2%) and oropharynx in 1 patient (4.2%).
      The clinical stage was stage IVA in 16 patients ( 66.7%) and IVB in 8 patients
      (33.3%). The overall response rates ie a combination of CR and PR was seen in
      11patients (45.8%). The pCR was seen in 15 patients (62.5%) and rest had near
      pCR. There was no linear coorelation between radiological size decrement and
      tumor response. On coorelation analysis the spearman correlation coefficent was 
      0.039 (P = 0.857). This suggest that presently used radiological response
      criterias for response assesment in head and neck cancers severly limit our
      ability to identify patients who would have pCR or near pCR. 

PMID- 24109523
TI  - Rectal ischemia mimicked tumor mass.
AB  - Ischemic proctitis is a rare disease which is usually encountered in elderly with
      comorbidities. We present a case of an 80-year old man with severe coronary
      disease who presented with severe hematochezia and hypotension. Endoscopy
      revealed a rectal mass 3-4 cm above the dental line and rectosigmoid mucosal
      inflammation compatible with ischemic colitis. The rectal insult was so intense
      that it resembled a neoplasmatic lesion. We discuss the causes, the prognostic
      factors, and the clinical and therapeutic challenges of this rare, albeit life
      threatening entity, and we review the relative literature. A percentage of 10%
      20% of patients with ischemic colitis usually have a distal potentially
      obstructing lesion or disorder such as cancer, diverticulitis or fecal impaction.
      Ischemic colitis, when mucosal and submucosal edema is severe and hemorrhagic
      nodules are large enough, can mimic a neoplasmatic lesion. The best treatment
      approach is a conservative management initially with a close clinical followup
      and after stabilization a repetition of rectal endoscopy with new biopsies. Early
      recognition of this clinical entity is of paramount importance to implement
      appropriate therapy (conservative or surgical) and avoid potentially fatal
      treatment of presumed inflammatory or infectious bowel diseases. 

PMID- 24109522
TI  - Postmastectomy radiation therapy: an overview for the practicing surgeon.
AB  - Locoregional control of breast cancer is the shared domain and responsibility of
      surgeons and radiation oncologists. Because surgeons are often the first
      providers to discuss locoregional control and recurrence risks with patients and
      because they serve in a key gatekeeping role as referring providers for radiation
      therapy, a sophisticated understanding of the evidence regarding radiotherapy in
      breast cancer management is essential for the practicing surgeon. This paper
      synthesizes the complex and evolving evidence regarding the role of radiation
      therapy after mastectomy. Although substantial evidence indicates that radiation
      therapy can reduce the risk of locoregional failure after mastectomy (with a
      relative reduction of risk of approximately two-thirds), debate persists
      regarding the specific subgroups who have sufficient risks of residual
      microscopic locoregional disease after mastectomy to warrant treatment with
      radiation. This paper reviews the evidence available to guide appropriate
      referral and patient decision making, with special attention to areas of
      controversy, including patients with limited nodal disease, those with large
      tumors but negative nodes, node-negative patients with high risk features,
      patients who have received systemic chemotherapy in the neoadjuvant setting, and
      patients who may wish to integrate radiation therapy with breast reconstruction
      surgery. 

PMID- 24109526
TI  - Recurrence of a t(8;21)-Positive Acute Myeloid Leukemia in the Form of a
      Granulocytic Sarcoma Involving Cranial Bones: A Diagnostic and Therapeutic
      Challenge.
AB  - Granulocytic sarcoma (GS) is a rare extramedullary solid tumor defined as an
      accumulation of myeloblasts or immature myeloid cells. It can cooccur with or
      precede the acute myeloid leukemia (AML) as well as following treated AML. The
      incidence of GS in AML patients is 3-8% but it significantly rises in M2 FAB
      subtype AML. This variety of AML harbors t(8;21) in up to 20-25% of cases
      (especially in children and black ones of African origin) and, at a molecular
      level, it is characterized by the generation of a fusion gene known as RUNX1
      RUNX1T1. Approximately 10% of M2 AML patients will develop GS, as a consequence,
      the t(8;21) and the relative transcript represent the most common cytogenetic and
      molecular abnormalities in GS. FLT3-ITD mutation was rarely described in AML
      patients presenting with GS. FLT3 ITD is generally strongly associated with poor
      prognosis in AML, and is rarely reported in patients with t(8;21). GS
      presentation is extremely variable depending on organs involved; in general,
      cranial bones and sinus are very rarely affected sites. We report a rare case of
      GS occurring as a recurrence of a previously treated t(8;21), FLT3-ITD positive
      AML, involving mastoid bones and paravertebral tissues. 

PMID- 24109527
TI  - Rapid Evolution to Blast Crisis Associated with a Q252H ABL1 Kinase Domain
      Mutation in e19a2 BCR-ABL1 Chronic Myeloid Leukaemia.
AB  - A minority of chronic myeloid leukaemia (CML) patients express variant
      transcripts of which the e19a2 BCR-ABL1 fusion is the most common. Instances of
      tyrosine kinase inhibitor (TKI) resistance in e19a2 BCR-ABL1 CML patients have
      rarely been reported. A case of e19a2 BCR-ABL1 CML is described in whom imatinib
      resistance, associated with a Q252H ABL1 kinase domain mutation, became apparent
      soon after initiation of TKI therapy. The patient rapidly transformed to myeloid
      blast crisis (BC) with considerable bone marrow fibrosis and no significant
      molecular response to a second generation TKI. The clinical course was
      complicated by comorbidities with the patient rapidly succumbing to advanced
      disease. This scenario of Q252H-associated TKI resistance with rapid BC
      transformation has not been previously documented in e19a2 BCR-ABL1 CML. This
      case highlights the considerable challenges remaining in the management of TKI
      resistant BC CML, particularly in the elderly patient. 

PMID- 24109528
TI  - Ventriculoperitoneal shunt peritoneal catheter knot formation.
AB  - The ventriculoperitoneal (VP) shunt is a common procedure in pediatric
      neurosurgery that carries a risk of complications at cranial and abdominal sites.
      We report on the case of a child with shunt infection and malfunction. The
      peritoneal catheter was tethered within the abdominal cavity, precluding its
      removal. Subsequently, laparoscopic exploration identified a knot at the distal
      end of the peritoneal catheter around the omentum. A new VP shunt was inserted
      after the infection was healed. This type of complication occurs rarely, so there
      are a limited number of case reports in the literature. This report is
      complemented by a literature review. 

PMID- 24109529
TI  - Native Valve Endocarditis due to Enterococcus hirae Presenting as a Neurological
      Deficit.
AB  - Enterococcus hirae is a rare isolate in clinical specimens. We describe a case of
      native aortic valve endocarditis in a 56-year-old man. This is the third reported
      case of endocarditis due to this organism, the first without recurrence of
      endocarditis and the first presenting as a neurological deficit. 

PMID- 24109530
TI  - Iron-Deficiency Anemia Leading to Transient Ischemic Attacks due to Intraluminal
      Carotid Artery Thrombus.
AB  - Reactive thrombocytosis secondary to iron-deficiency anemia (IDA) is a rare but
      recognized cause of stroke. We report the case of a patient with iron-deficiency
      anemia presenting with multiple transient ischemic attacks (TIA) due to
      intraluminal thrombus of an internal carotid artery. The putative mechanisms
      underlying anemia and stroke syndromes are not completely understood, and it is
      believed that iron deficiency may cause ischemic stroke by several potential
      mechanisms. Thrombocytosis is often associated with iron deficiency, and
      microcytosis produces a reduction in the red cell deformability and could produce
      a hypercoagulable state. The platelet count and function observed in iron
      deficiency anemia could act synergistically to promote thrombus formation,
      especially in the setting of an underlying atherosclerotic disease. The presence
      of floating thrombus in a patient with clinical and MRI evidence of stroke
      represents a significant therapeutic dilemma and requires immediate decision
      about treatment. 

PMID- 24109531
TI  - Emergency excision of cardiac myxoma and endovascular coiling of intracranial
      aneurysm after cerebral infarction.
AB  - Cardiac myxoma is the most common primary tumor of the heart, located mainly in
      the left atrium. Cerebral embolization or intracranial aneurysm formation as a
      consequence of left atrial myxomas has been well documented, whereas myxoma
      embolization causing the combination of cerebral infarction and intracranial
      myxomatous aneurysm is rare. We report herein, a 67-year-old female with a
      cardiac myxoma who experienced a left hemispheric embolic ischemic stroke and in
      addition was found to have right internal carotid artery aneurysm. The patient
      underwent emergency surgical excision of left atrial myxoma 2 hours after the
      stroke onset and endovascular coiling of the aneurysm a week later. Although the
      timing of cardiac surgery is controversial in patients who have had recent
      ischemic stroke, we recommend immediate resection of cardiac myxoma, if feasible,
      and early endovascular treatment of associated intracranial myxomatous aneurysms.

PMID- 24109532
TI  - An unusual extremely distant noncommunicating uterine horn with myoma and
      adenomyosis treated with laparoscopic hemihysterectomy.
AB  - A 41-year-old woman referred to us with dysmenorrhea and severe pelvic pain
      although she was previously submitted to right laparotomic adnexectomy for
      ovarian endometrioma and to a subsequent operative laparoscopy for pelvic
      adhesions. After ultrasound examination, the patient underwent diagnostic
      hysteroscopy and operative laparoscopy which confirmed the clinic suspect of an
      unicornuate uterus. However, it was very unusual to see an extremely distanced
      right horn, without communication with uterus, without adnexa, and with a small
      myoma belonging to it. Moreover, omentum and bowel were attached to fundus of
      right horn and thick adhesions fixed it to rectum and right pelvic wall.
      Therefore, identification of anatomical structures was difficult, as it was
      extremely arduous to isolate the ureter, which was involved inside the adhesions
      surrounding the right uterine horn. Nevertheless, laparoscopic right
      hemihysterectomy was successfully performed and right horn was sent to our
      pathologist who recognized hypotrophic endometrium and adenomyosis. 

PMID- 24109533
TI  - Urethral mucosa prolapse in an 18-year-old adolescent.
AB  - Urethra mucosa prolapse is a benign condition in which there is a circular
      protrusion of the distal urethra through the external urethra meatus. It is more
      commonly seen in prepubertal black girls and postmenopausal white women. It is
      rare in the reproductive age group. This case describes the presentation and
      management of an 18-year-old adolescent with urethra mucosa prolapse. 

PMID- 24109534
TI  - Two Live Births following Robotic-Assisted Abdominal Cerclage in Nonpregnant
      Women.
AB  - Introduction. To report the robotic-assisted abdominal cerclage performed in two
      nonpregnant women and the success of live birth outcomes. Presentation of Cases.
      A 36-year-old woman with a complaint of recurrent second trimester pregnancy
      losses and a 35-year-old patient with a complaint of preterm deliveries and
      cervical insufficiency underwent robotic assisted abdominal cervicoisthmic
      cerclage placement in nonpregnant period. The two patients had spontaneous
      pregnancy after the robotic-assisted abdominal cerclage and delivered healthy
      infants. Discussion. The limitations of traditional laparoscopic abdominal
      cerclage have been accomplished with robotic surgery advantages especially
      intuitive movements and increased range of motion. There are only a few studies
      in the literature including robotic assisted abdominal cerclage in nonpregnant
      women, and only five successful live birth outcomes were reported. In this paper,
      we reported the sixth and seventh cases of achieved live pregnancy after robotic
      assisted abdominal cerclage in the literature. Conclusion. Robotic assisted
      abdominal cerclage is a good alternative surgical method with successful
      pregnancy outcomes. 

PMID- 24109535
TI  - Extramedullary hematopoiesis in the uterine cervix associated with tissue repair.
AB  - Extramedullary hematopoiesis (EMH) is the presence of hematopoietic precursors
      outside the bone marrow. This condition is usually associated with hematologic
      disorders. Although EMH can be found in almost every site in the body, female
      genital tract involvement is rare. The authors report EMH in the uterine cervix
      from a 64-year-old patient following cervical biopsy due to abnormal cervical
      cytology. Neither neoplasm nor hematologic disorder was detected before the
      diagnosis and after 1 year of follow up. To the best of our knowledge, this is
      the first reported case of EMH involving the uterine cervix which showed an
      association with tissue repair. 

PMID- 24109536
TI  - Diagnosis of primary langerhans cell histiocytosis of the vulva in a
      postmenopausal woman.
AB  - Langerhans cell histiocytosis (LCH) is a very rare disease of female genital
      tract, most commonly seen in vulva and unusual in postmenopausal period. Herein,
      we report the 8th case of pure vulvar LCH in a postmenopausal woman. We pay
      attention to the differential diagnosis in postmenopausal state, features of
      pathologic diagnosis, and treatment options. 

PMID- 24109537
TI  - Management of Cervical Fibroid during the Reproductive Period.
AB  - This is a case report of a 29-year-old lady who presented with excessive vaginal
      discharge and sessile cervical fibroid arising from the vaginal portion of the
      cervix. She was not suitable for uterine artery embolization as she has never
      previously been pregnant before. She was encouraged to get pregnant and to avoid
      surgical excision which can lead to hysterectomy. Shortly after, she became
      pregnant. She had many admissions during pregnancy due to bleeding from the
      fibroid, and in one occasion she had blood transfusions. The fibroid increased in
      size to become larger than the head of the baby. An emergency caesarean section
      was performed at 37 weeks when she attended in labour before the date of her
      elective caesarean section. She was managed conservatively following delivery in
      the hope that the fibroid becomes smaller making surgery easier. The fibroid
      degenerated and reduced in size. Vaginal myomectomy was carried out. The patient
      is now pregnant for the second time and had a cervical suture at 20 weeks
      gestation. In this educational case report we discuss the different management
      options of cervical fibroids and review the literature of other similar cases and
      their outcome. 

PMID- 24109538
TI  - Choroidal metastasis of non-small cell lung cancer that responded to gefitinib.
AB  - A 52-year-old Japanese woman presented with optical symptoms, including left
      sided myodesopsia, blurred vision, narrowed visual field, and diminished visual
      acuity. Ocular evaluation revealed a metastatic tumor in the choroid. Further
      examinations identified pulmonary adenocarcinoma as the primary tumor. Because an
      epidermal growth factor receptor gene (EGFR) mutation was detected in a biopsy
      specimen, gefitinib treatment was initiated. Dramatic responses were obtained in
      the primary tumor and metastatic foci. Optical symptoms improved and remained
      stable for 5 months during the treatment, until relapse. This report demonstrates
      that gefitinib is effective for choroidal metastasis of pulmonary adenocarcinoma
      harboring an EGFR mutation. 

PMID- 24109539
TI  - Inflammation in retinal disease.

PMID- 24109540
TI  - On the relevance of an argument as regards the role of existential suffering in
      the end-of-life context.

PMID- 24109541
TI  - Stability Studies of Thiocolchicoside in Bulk and Capsules Using RP
      HPTLC/Densitometry.
AB  - A new stability-indicating reversed-phase high-performance thin-layer
      chromatographic (RP-HPTLC) method for densitometric analysis of thiocolchicoside
      was developed and validated. The chromatograms were developed using aluminum
      plates pre-coated with silica gel 60 RP-18 F254S as a stationary phase and
      methanol : water (70 : 30 v/v) as a mobile phase. The compact band for
      thiocolchicoside was observed at R f value of 0.60 +/- 0.02 at an absorption
      wavelength of 377 nm. The linear regression data for the calibration plots (r (2)
      = 0.9984) was found with respect to peak area in the concentration range of 100
      600 ng per band. The limit of detection (LOD) and limit of quantification (LOQ)
      were 9.77 ng and 29.63 ng, respectively. The drug was exposed to acidic and
      alkaline hydrolysis, oxidation, photo degradation, and dry heat conditions. The
      peaks of degradation products were well-resolved from the peak of the standard
      drug with significantly different R f values. Statistical analysis proved that
      the established RP-HPTLC method is reproducible, selective, and accurate for the
      determination of thiocolchicoside in its formulations. The method can effectively
      separate the drug from its degradation products, and it can be considered as
      stability-indicating assay. 

PMID- 24109542
TI  - Adsorptive cathodic stripping voltammetric determination of cefoperazone in bulk
      powder, pharmaceutical dosage forms, and human urine.
AB  - The electroreduction behaviour and determination of cefoperazone using a hanging
      mercury drop electrode were investigated. Cyclic voltammograms of cefoperazone
      recorded in universal Britton-Robinson buffers pH 3-6 exhibited a single
      irreversible cathodic peak. The process was adsorption-controlled. Britton
      Robinson buffer 0.04 M pH 4.0 was selected as a supporting electrolyte for
      quantitative purposes by differential pulse and square wave adsorptive cathodic
      stripping voltammetry. The experimental voltammetric conditions were optimized
      using Central Composite Face design. A reduction wave was seen in the range from 
      0.7 to -0.8 V. These voltammetric techniques were successfully validated as per
      ICH guidelines and applied for the determination of cefoperazone in its single
      and sulbactam containing powders for injection and statistically comparable to
      USP-HPLC. They were further extended to determine cefoperazone in spiked human
      urine with no matrix effect. 

PMID- 24109543
TI  - Periodontal status among adolescents in Georgia. A pathfinder study.
AB  - Objectives. The aim of the present pathfinder study was to screen and map the
      periodontal status of Georgian population in accordance with the guidelines of
      the World Health Organization for population based surveys. Methods. During 2012,
      a pathfinder study was conducted to collect this data. For the periodontal
      portion of the study, 15-year-old school children were examined in the capital
      city of Tbilisi as well as in two other large cities and 4 smaller villages. All
      participants were examined by a trained dental team in a classroom using a dental
      mirror and a periodontal probe. Periodontal examination included plaque scores,
      calculus scores, probing depth measurements and bleeding on probing. These
      measurements were recorded for the Ramfjord index teeth. Results. A total of 397
      15-year-old participants were examined in this pathfinder study. There were 240
      females (60.45%) and 157 males (39.55%). Of the total participants 196 (49.37%)
      were urban adolescents while 201 (50.63%) were from rural communities. Mean
      probing depth was 3.34 +/- 0.57 mm with a range of 1 to 10 mm; a relatively high
      proportion (34.26%) of these subjects presented with at least one site with
      pockets of 5 mm or deeper. Males presented with greater plaque, calculus and
      probing depths than females. When urban and rural populations were compared,
      urban participants presented with more plaque, probing depths and bleeding on
      probing. Greater pocket depths were found to be related to the presence of plaque
      calculus and bleeding on probing. Conclusions. Overall, rather high incidences of
      periodontal pockets >= 5 mm were detected in this population. This data should
      serve to prepare further more detailed epidemiological studies that will serve to
      plan and implement prevent and treat strategies for periodontal diseases in
      Georgia and also help make manpower decisions. 

PMID- 24109544
TI  - Between tide and wave marks: a unifying model of physical zonation on littoral
      shores.
AB  - The effects of tides on littoral marine habitats are so ubiquitous that
      shorelines are commonly described as 'intertidal', whereas waves are considered a
      secondary factor that simply modifies the intertidal habitat. However mean
      significant wave height exceeds tidal range at many locations worldwide. Here we
      construct a simple sinusoidal model of coastal water level based on both tidal
      range and wave height. From the patterns of emergence and submergence predicted
      by the model, we derive four vertical shoreline benchmarks which bracket up to
      three novel, spatially distinct, and physically defined zones. The (1) emergent
      tidal zone is characterized by tidally driven emergence in air; the (2) wave zone
      is characterized by constant (not periodic) wave wash; and the (3) submergent
      tidal zone is characterized by tidally driven submergence. The decoupling of
      tidally driven emergence and submergence made possible by wave action is a
      critical prediction of the model. On wave-dominated shores (wave height ? tidal
      range), all three zones are predicted to exist separately, but on tide-dominated
      shores (tidal range ? wave height) the wave zone is absent and the emergent and
      submergent tidal zones overlap substantially, forming the traditional "intertidal
      zone". We conclude by incorporating time and space in the model to illustrate
      variability in the physical conditions and zonation on littoral shores. The
      wave:tide physical zonation model is a unifying framework that can facilitate our
      understanding of physical conditions on littoral shores whether tropical or
      temperate, marine or lentic. 

PMID- 24109545
TI  - Publication trends in neuroimaging of minimally conscious states.
AB  - We used existing and customized bibliometric and scientometric methods to analyze
      publication trends in neuroimaging research of minimally conscious states and
      describe the domain in terms of its geographic, contributor, and content
      features. We considered publication rates for the years 2002-2011, author
      interconnections, the rate at which new authors are added, and the domains that
      inform the work of author contributors. We also provided a content analysis of
      clinical and ethical themes within the relevant literature. We found a 27% growth
      in the number of papers over the period of study, professional diversity among a
      wide range of peripheral author contributors but only few authors who dominate
      the field, and few new technical paradigms and clinical themes that would
      fundamentally expand the landscape. The results inform both the science of
      consciousness as well as parallel ethics and policy studies of the potential for
      translational challenges of neuroimaging in research and health care of people
      with disordered states of consciousness. 

PMID- 24109546
TI  - The controlled imitation task: a new paradigm for studying self-other control.
AB  - In the automatic imitation task (AIT) participants make a cued response during
      simultaneous exposure to a congruent or incongruent action made by another agent.
      Participants are slower to make the cued response on incongruent trials, which is
      thought to reflect conflict between the motor representation activated by the cue
      and the motor representation activated by the observed action. On incongruent
      trials, good performance requires the capacity to suppress the imitative action,
      in favor of producing the cued response. Here, we introduce a new experimental
      paradigm that complements the AIT, and is therefore a useful task for studying
      the control of self and other activated representations. In what we term the
      "Controlled Imitation Task (CIT)", participants are cued to make an action, but
      on 50% of trials, within 100 ms of this cue, an on-screen hand makes a congruent
      or incongruent action. If the onscreen hand moves, the participant must suppress
      the cued response, and instead imitate the observed action as quickly and
      accurately as possible. In direct contrast to the AIT, the CIT requires
      suppression of a self-activated motor representation, and prioritization of an
      imitative response. In experiment 1, we report a robust pattern of interference
      effects in the CIT, such that participants are slower to make the imitative
      response on incongruent compared to congruent trials. In experiment 2, we
      replicate this effect while including a non-imitative spatial-cue control
      condition to show that the effect is particularly robust for imitative response
      tendencies per se. Owing to the essentially opposite control requirements of the
      CIT versus the AIT (i.e., suppression of self-activated motor representations
      instead of suppression of other-activated motor representations), we propose that
      this new task is a potentially informative complementary paradigm to the AIT that
      can be used in studies of self-other control processes. 

PMID- 24109547
TI  - MiR-184 regulates insulin secretion through repression of Slc25a22.
AB  - Insulin secretion from pancreatic beta-cells plays an essential role in blood
      glucose homeostasis and type 2 diabetes. Many genes are involved in the secretion
      of insulin and most of these genes can be targeted by microRNAs (miRNAs).
      However, the role of miRNAs in insulin secretion and type 2 diabetes has not been
      exhaustively studied. The expression miR-184, a miRNA enriched in pancreatic
      islets, negatively correlates with insulin secretion, suggesting that it is a
      good candidate for miRNA-mediated regulation of insulin secretion. Here we report
      that miR-184 inhibits insulin secretion in the MIN6 pancreatic beta-cell line
      through the repression of its target Slc25a22, a mitochondrial glutamate carrier.
      Our study provides new insight into the regulation of insulin secretion by
      glutamate transport in mitochondria. 

PMID- 24109548
TI  - Microgeographic maladaptive performance and deme depression in response to roads
      and runoff.
AB  - Despite theoretical understanding and empirical detection of local adaptation in
      natural environments, our knowledge of such divergence in fragmented habitats
      remains limited, especially in the context of microgeographic spatial scales and
      contemporary time scales. I used a combination of reciprocal transplant and
      common garden exposure experiments to evaluate potential microgeographic
      divergence in a pool-breeding amphibian occupying a landscape fragmented by
      roads. As indicated by reduced rates of survival and increased rates of
      malformation, I found evidence for maladaptation in road adjacent populations.
      This response is in direct counterpoint to recently described local adaption by a
      cohabiting species of amphibian. These results suggest that while divergence
      might commonly follow habitat modification, the direction of its outcome cannot
      be generalized even in identical habitats. Further, maladaptive responses can be
      associated with a more generalized depression effect that transcends the local
      environment. Alongside recent reports, these results suggest that maladaptive
      responses may be an emerging consequence of human-induced environmental change.
      Thus future studies should carefully consider the population unit as a key level
      for inference. 

PMID- 24109549
TI  - Using cloud-based mobile technology for assessment of competencies among medical
      students.
AB  - Valid, direct observation of medical student competency in clinical settings
      remains challenging and limits the opportunity to promote performance-based
      student advancement. The rationale for direct observation is to ascertain that
      students have acquired the core clinical competencies needed to care for
      patients. Too often student observation results in highly variable evaluations
      which are skewed by factors other than the student's actual performance. Among
      the barriers to effective direct observation and assessment include the lack of
      effective tools and strategies for assuring that transparent standards are used
      for judging clinical competency in authentic clinical settings. We developed a
      web-based content management system under the name, Just in Time Medicine (JIT),
      to address many of these issues. The goals of JIT were fourfold: First, to create
      a self-service interface allowing faculty with average computing skills to author
      customizable content and criterion-based assessment tools displayable on internet
      enabled devices, including mobile devices; second, to create an assessment and
      feedback tool capable of capturing learner progress related to hundreds of
      clinical skills; third, to enable easy access and utilization of these tools by
      faculty for learner assessment in authentic clinical settings as a means of just
      in time faculty development; fourth, to create a permanent record of the
      trainees' observed skills useful for both learner and program evaluation. From
      July 2010 through October 2012, we implemented a JIT enabled clinical evaluation
      exercise (CEX) among 367 third year internal medicine students. Observers
      (attending physicians and residents) performed CEX assessments using JIT to guide
      and document their observations, record their time observing and providing
      feedback to the students, and their overall satisfaction. Inter-rater reliability
      and validity were assessed with 17 observers who viewed six videotaped student
      patient encounters and by measuring the correlation between student CEX scores
      and their scores on subsequent standardized-patient OSCE exams. A total of 3567
      CEXs were completed by 516 observers. The average number of evaluations per
      student was 9.7 (+/-1.8 SD) and the average number of CEXs completed per observer
      was 6.9 (+/-15.8 SD). Observers spent less than 10 min on 43-50% of the CEXs and
      68.6% on feedback sessions. A majority of observers (92%) reported satisfaction
      with the CEX. Inter-rater reliability was measured at 0.69 among all observers
      viewing the videotapes and these ratings adequately discriminated competent from
      non-competent performance. The measured CEX grades correlated with subsequent
      student performance on an end-of-year OSCE. We conclude that the use of JIT is
      feasible in capturing discrete clinical performance data with a high degree of
      user satisfaction. Our embedded checklists had adequate inter-rater reliability
      and concurrent and predictive validity. 

PMID- 24109550
TI  - When given the opportunity, chimpanzees maximize personal gain rather than "level
      the playing field".
AB  - We provided chimpanzees (Pan troglodytes) with the ability to improve the quality
      of food rewards they received in a dyadic test of inequity. We were interested to
      see if this provision influenced their responses and, if so, whether it was
      mediated by a social partner's outcomes. We tested eight dyads using an exchange
      paradigm in which, depending on the condition, the chimpanzees were rewarded with
      either high-value (a grape) or low-value (a piece of celery) food rewards for
      each completed exchange. We included four conditions. In the first, "Different"
      condition, the subject received different, less-preferred, rewards than their
      partner for each exchange made (a test of inequity). In the "Unavailable"
      condition, high-value rewards were shown, but not given, to both chimpanzees
      prior to each exchange and the chimpanzees were rewarded equally with low-value
      rewards (a test of individual contrast). The final two conditions created equity.
      In these High-value and Low-value "Same" conditions both chimpanzees received the
      same food rewards for each exchange. Within each condition, the chimpanzees first
      completed ten trials in the Baseline Phase, in which the experimenter determined
      the rewards they received, and then ten trials in the Test Phase. In the Test
      Phase, the chimpanzees could exchange tokens through the aperture of a small
      wooden picture frame hung on their cage mesh in order to receive the high-value
      reward. Thus, in the Test Phase, the chimpanzees were provided with an
      opportunity to improve the quality of the rewards they received, either
      absolutely or relative to what their partner received. The chimpanzees responded
      in a targeted manner; in the Test Phase they attempted to maximize their returns
      in all conditions in which they had received low-value rewards during the
      Baseline Phase. Thus, the chimpanzees were apparently motivated to increase their
      reward regardless of their partners', but they only used the mechanism provided
      when it afforded the opportunity for them to increase their rewards. We also
      found evidence that the chimpanzees' responses were enhanced by social
      facilitation. Specifically, the chimpanzees were more likely to exchange their
      tokens through the frame when their test partner also did so, even in
      circumstances in which their reward value could not be improved. Our paradigm
      provided the chimpanzees with the possibility to improve the quality of rewards
      they received in the Test Phase. We found that refusals - to exchange tokens or
      to eat rewards - decreased significantly in the Test Phase compared to the
      Baseline Phase, where no such opportunity for improvement of outcomes existed.
      Thus, the chimpanzees participated more when they could improve the rewards they
      received. 

PMID- 24109551
TI  - Mind the gaps: investigating the cause of the current range disjunction in the
      Cape Platanna, Xenopus gilli (Anura: Pipidae).
AB  - Low-lying areas of the Cape at Africa's south-westernmost tip have undergone
      dramatic marine-remodelling, with regular changes in sea-level following glacial
      cycles. Species for which marine barriers are impenetrable underwent concomitant
      radical distribution changes which may account for current range disjunctions.
      The Cape platanna, Xenopus gilli, is a frog distributed in only three disjunt
      areas within low-lying regions of the southwestern Cape. We determined the
      relationship between frogs from these three disjunct areas, by using a
      combination of morphometric analysis and mtDNA (ND2 and 16S fragments) sequences
      of 130 frogs from eight ponds. Coalescent analyses on molecular data dated the
      divergence in two major clades to around 4.6 Mya, a period during which major
      uplifting on the eastern side of the subcontinent caused climate changes
      throughout southern Africa. Principal components analysis showed significant
      morphometric differences between each clade on head and limb measurements.
      Consistent differences in ventral colouration and patterning were also observed.
      We report on increased levels of hybridisation with X. laevis throughout the
      range of X. gilli, which reaches at least 27% hybrids in some ponds. Urgent
      conservation actions are required to control habitat loss from alien invasive
      vegetation, and prevent introgression with the domestic-exotic, X. laevis. 

PMID- 24109553
TI  - Prescribing of psychotropic medications to the elderly population of a Canadian
      province: a retrospective study using administrative databases.
AB  - Background. Psychotropic medications, in particular second-generation
      antipsychotics (SGAs) and benzodiazepines, have been associated with harm in
      elderly populations. Health agencies around the world have issued warnings about
      the risks of prescribing such medications to frail individuals affected by
      dementia and current guidelines recommend their use only in cases where the
      benefits clearly outweigh the risks. This study documents the use of psychotropic
      medications in the entire elderly population of a Canadian province in the
      context of current clinical guidelines for the treatment of behavioural
      disturbances. Methods. Prevalent and incident utilization of antipsychotics,
      benzodiazepines and related medications (zopiclone and zaleplon) were determined
      in the population of Manitobans over age 65 in the time period 1997/98 to 2008/09
      fiscal years. Comparisons between patients living in the community and those
      living in personal care (nursing) homes (PCH) were conducted. Influence of
      sociodemographic characteristics on prescribing was assessed by generalized
      estimating equations. Non-optimal use was defined as the prescribing of high dose
      of antipsychotic medications and the use of combination therapy of a
      benzodiazepine (or zopiclone/zaleplon) with an antipsychotic. A decrease in
      intensity of use over time and lower proportions of patients treated with
      antipsychotics at high dose or in combination with benzodiazepines (or
      zopiclone/zaleplon) was considered a trend toward better prescribing. Multiple
      regression analysis determined predictors of non-optimal use in the elderly
      population. Results. A 20-fold greater prevalent utilization of SGAs was observed
      in PCH-dwelling elderly persons compared to those living in the community. In
      2008/09, 27% of PCH-dwelling individuals received a prescription for an SGA.
      Patient characteristics, such as younger age, male gender, diagnoses of dementia
      (or use of an acetylcholinesterase inhibitor) or psychosis in the year prior the
      prescription, were predictors of non-optimal prescribing (e.g., high dose
      antipsychotics). During the period 2002/3 and 2007/8, amongst new users of SGAs,
      10.2% received high doses. Those receiving high dose antipsychotics did not show
      high levels of polypharmacy. Conclusions. Despite encouraging trends, the use of
      psychotropic medications remains high in elderly individuals, especially in
      residents of nursing homes. Clinicians caring for such patients need to carefully
      assess risks and benefits. 

PMID- 24109554
TI  - Behavioral niche partitioning in a sympatric tiger beetle assemblage and
      implications for the endangered Salt Creek tiger beetle.
AB  - How behavioral patterns are related to niche partitioning is an important
      question in understanding how closely related species within ecological
      communities function. Behavioral niche partitioning associated with
      thermoregulation is well documented in tiger beetles as a group. Co-occurring
      species of salt flat tiger beetles have adapted many thermoregulatory behaviors
      to cope with this harsh ecosystem. On first examination these beetles appear to
      occur in overlapping microhabitats and therefore compete for resources. To
      determine if behavioral niche partitioning is allowing multiple species to occur
      within the same harsh salt flat ecosystem we observed Cicindela nevadica
      lincolniana, Cicindela circumpicta, Cicindela fulgida, and Cicindela togata
      between 8:00 h and 21:00 h and recorded all behaviors related to thermoregulation
      using a digital voice recorder. Results of this study strongly indicate that
      competition among these species for resources has been reduced by the adaptation
      of different thermoregulatory behaviors such as spending time in shallow water,
      avoiding the sun during the hottest parts of the day, and by positioning their
      body against or away from the soil. The endangered C. n. lincolniana appears to
      rely most heavily on the shallow water of seeps for their diurnal foraging
      behavior (potentially limiting their foraging habitat), but with the advantage of
      allowing foraging during the hottest times of the day when potential competitors
      are less frequent. Ironically, this association also may help explain C. n.
      lincolniana's susceptibility to extinction: beyond the loss of saline wetlands
      generally, limited seeps and pools even within remaining saline habitat may
      represent a further habitat limitation within an already limited habitat. 

PMID- 24109552
TI  - Galaxy tools and workflows for sequence analysis with applications in molecular
      plant pathology.
AB  - The Galaxy Project offers the popular web browser-based platform Galaxy for
      running bioinformatics tools and constructing simple workflows. Here, we present
      a broad collection of additional Galaxy tools for large scale analysis of gene
      and protein sequences. The motivating research theme is the identification of
      specific genes of interest in a range of non-model organisms, and our central
      example is the identification and prediction of "effector" proteins produced by
      plant pathogens in order to manipulate their host plant. This functional
      annotation of a pathogen's predicted capacity for virulence is a key step in
      translating sequence data into potential applications in plant pathology. This
      collection includes novel tools, and widely-used third-party tools such as NCBI
      BLAST+ wrapped for use within Galaxy. Individual bioinformatics software tools
      are typically available separately as standalone packages, or in online browser
      based form. The Galaxy framework enables the user to combine these and other
      tools to automate organism scale analyses as workflows, without demanding
      familiarity with command line tools and scripting. Workflows created using Galaxy
      can be saved and are reusable, so may be distributed within and between research
      groups, facilitating the construction of a set of standardised, reusable
      bioinformatic protocols. The Galaxy tools and workflows described in this
      manuscript are open source and freely available from the Galaxy Tool Shed
      (http://usegalaxy.org/toolshed or http://toolshed.g2.bx.psu.edu). 

PMID- 24109555
TI  - iSNO-AAPair: incorporating amino acid pairwise coupling into PseAAC for
      predicting cysteine S-nitrosylation sites in proteins.
AB  - As one of the most important and universal posttranslational modifications (PTMs)
      of proteins, S-nitrosylation (SNO) plays crucial roles in a variety of biological
      processes, including the regulation of cellular dynamics and many signaling
      events. Knowledge of SNO sites in proteins is very useful for drug development
      and basic research as well. Unfortunately, it is both time-consuming and costly
      to determine the SNO sites purely based on biological experiments. Facing the
      explosive protein sequence data generated in the post-genomic era, we are
      challenged to develop automated vehicles for timely and effectively determining
      the SNO sites for uncharacterized proteins. To address the challenge, a new
      predictor called iSNO-AAPair was developed by taking into account the coupling
      effects for all the pairs formed by the nearest residues and the pairs by the
      next nearest residues along protein chains. The cross-validation results on a
      state-of-the-art benchmark have shown that the new predictor outperformed the
      existing predictors. The same was true when tested by the independent proteins
      whose experimental SNO sites were known. A user-friendly web-server for iSNO
      AAPair was established at http://app.aporc.org/iSNO-AAPair/, by which users can
      easily obtain their desired results without the need to follow the mathematical
      equations involved during its development. 

PMID- 24109556
TI  - Goats favour personal over social information in an experimental foraging task.
AB  - Animals can use their environments more efficiently by selecting particular
      sources of information (personal or social), according to specific situations.
      Group-living animals may benefit from gaining information based on the behaviour
      of other individuals. Indeed, social information is assumed to be faster and less
      costly to use than personal information, thus increasing foraging efficiency.
      However, when food sources change seasonally or are randomly distributed,
      individual information may become more reliable than social information. The aim
      of this study was to test the use of conflicting personal versus social
      information in goats (Capra hircus), in a foraging task. We found that goats
      relied more on personal than social information, when both types of information
      were available and in conflict. No effect of social rank was found on the
      occasions when goats followed other demonstrator goats. Goats are selective
      browsers/grazers and therefore relying on personal rather than social information
      could be the most efficient way to find patchily distributed resources in highly
      variable environments. Studies testing specific assumptions regarding the use of
      different sources of information can extend our understanding of decision making,
      including observed patterns of social learning. 

PMID- 24109557
TI  - Why do leaf-tying caterpillars abandon their leaf ties?
AB  - Leaf-tying caterpillars act as ecosystem engineers by building shelters between
      overlapping leaves, which are inhabited by other arthropods. Leaf-tiers have been
      observed to leave their ties and create new shelters (and thus additional
      microhabitats), but the ecological factors affecting shelter fidelity are poorly
      known. For this study, we explored the effects of resource limitation and
      occupant density on shelter fidelity and assessed the consequences of shelter
      abandonment. We first quantified the area of leaf material required for a
      caterpillar to fully develop for two of the most common leaf-tiers that feed on
      white oak, Quercus alba. On average, Psilocorsis spp. caterpillars consumed 21.65
      +/- 0.67 cm(2) leaf material to complete development. We also measured the area
      of natural leaf ties found in a Maryland forest, to determine the distribution of
      resources available to caterpillars in situ. Of 158 natural leaf ties examined,
      47% were too small to sustain an average Psilocorsis spp. caterpillar for the
      entirety of its development. We also manipulated caterpillar densities within
      experimental ties on potted trees to determine the effects of cohabitants on the
      likelihood of a caterpillar to leave its tie. We placed 1, 2, or 4 caterpillars
      in ties of a standard size and monitored the caterpillars twice daily to track
      their movement. In ties with more than one occupant, caterpillars showed a
      significantly greater propensity to leave their tie, and left sooner and at a
      faster rate than those in ties as single occupants. To understand the
      consequences of leaf tie abandonment, we observed caterpillars searching a tree
      for a site to build a shelter in the field. This is a risky behavior, as 17% of
      the caterpillars observed died while searching for a shelter site. Caterpillars
      that successfully built a shelter traveled 110 +/- 20 cm and took 28 +/- 7 min to
      find a suitable site to build a shelter. In conclusion, leaf-tying caterpillars
      must frequently abandon their leaf tie due to food limitation and interactions
      with other caterpillars, but this is a costly behavior. 

PMID- 24109558
TI  - The beta-carboline alkaloid harmine inhibits telomerase activity of MCF-7 cells
      by down-regulating hTERT mRNA expression accompanied by an accelerated senescent
      phenotype.
AB  - The end replication problem, which occurs in normal somatic cells inducing
      replicative senescence, is solved in most cancer cells by activating telomerase.
      The activity of telomerase is highly associated with carcinogenesis which makes
      the enzyme an attractive biomarker in cancer diagnosis and treatment. The indole
      alkaloid harmine has multiple pharmacological properties including DNA
      intercalation which can lead to frame shift mutations. In this study, harmine was
      applied to human breast cancer MCF-7 cells. Its activity towards telomerase was
      analyzed by utilizing the telomeric repeat amplification protocol (TRAP). Our
      data indicate that harmine exhibits a pronounced cytotoxicity and induces an anti
      proliferation state in MCF-7 cells which is accompanied by a significant
      inhibition of telomerase activity and an induction of an accelerated senescence
      phenotype by over-expressing elements of the p53/p21 pathway. 

PMID- 24109559
TI  - Data reuse and the open data citation advantage.
AB  - Background. Attribution to the original contributor upon reuse of published data
      is important both as a reward for data creators and to document the provenance of
      research findings. Previous studies have found that papers with publicly
      available datasets receive a higher number of citations than similar studies
      without available data. However, few previous analyses have had the statistical
      power to control for the many variables known to predict citation rate, which has
      led to uncertain estimates of the "citation benefit". Furthermore, little is
      known about patterns in data reuse over time and across datasets. Method and
      Results. Here, we look at citation rates while controlling for many known
      citation predictors and investigate the variability of data reuse. In a
      multivariate regression on 10,555 studies that created gene expression microarray
      data, we found that studies that made data available in a public repository
      received 9% (95% confidence interval: 5% to 13%) more citations than similar
      studies for which the data was not made available. Date of publication, journal
      impact factor, open access status, number of authors, first and last author
      publication history, corresponding author country, institution citation history,
      and study topic were included as covariates. The citation benefit varied with
      date of dataset deposition: a citation benefit was most clear for papers
      published in 2004 and 2005, at about 30%. Authors published most papers using
      their own datasets within two years of their first publication on the dataset,
      whereas data reuse papers published by third-party investigators continued to
      accumulate for at least six years. To study patterns of data reuse directly, we
      compiled 9,724 instances of third party data reuse via mention of GEO or
      ArrayExpress accession numbers in the full text of papers. The level of third
      party data use was high: for 100 datasets deposited in year 0, we estimated that
      40 papers in PubMed reused a dataset by year 2, 100 by year 4, and more than 150
      data reuse papers had been published by year 5. Data reuse was distributed across
      a broad base of datasets: a very conservative estimate found that 20% of the
      datasets deposited between 2003 and 2007 had been reused at least once by third
      parties. Conclusion. After accounting for other factors affecting citation rate,
      we find a robust citation benefit from open data, although a smaller one than
      previously reported. We conclude there is a direct effect of third-party data
      reuse that persists for years beyond the time when researchers have published
      most of the papers reusing their own data. Other factors that may also contribute
      to the citation benefit are considered. We further conclude that, at least for
      gene expression microarray data, a substantial fraction of archived datasets are
      reused, and that the intensity of dataset reuse has been steadily increasing
      since 2003. 

PMID- 24109561
TI  - Internet-delivered therapist-guided physical activity for mild to moderate
      depression: a randomized controlled trial.
AB  - Objective. The main hypothesis, and the objective of the study, was to test if
      the participants allocated to the treatment group would show a larger reduction
      in depressive symptoms than those in the control group. Methods. This study was a
      randomized nine week trial of an Internet-administered treatment based on guided
      physical exercise for Major Depressive Disorder (MDD). A total of 48 participants
      with mild to moderate depression, diagnosed using the Structured Clinical
      Interview for DSM-IV Axis I Disorders, were randomized either to a treatment
      intervention or to a waiting-list control group. The main outcome measure for
      depression was the Beck Depression Inventory-II (BDI-II), and physical activity
      level was measured using the International Physical Activity Questionnaire
      (IPAQ). The treatment program consisted of nine text modules, and included
      therapist guidance on a weekly basis. Results. The results showed significant
      reductions of depressive symptoms in the treatment group compared to the control
      group, with a moderate between-group effect size (Cohen's d = 0.67; 95%
      confidence interval: 0.09-1.25). No difference was found between the groups with
      regards to increase of physical activity level. For the treatment group, the
      reduction in depressive symptoms persisted at six months follow-up. Conclusions.
      Physical activity as a treatment for depression can be delivered in the form of
      guided Internet-based self-help. Trial Registration. The trial was registered at
      ClinicalTrials.gov (NCT01573130). 

PMID- 24109562
TI  - Fuzzy inference game approach to uncertainty in business decisions and market
      competitions.
AB  - The increasing challenges and complexity of business environments are making
      business decisions and operations more difficult for entrepreneurs to predict the
      outcomes of these processes. Therefore, we developed a decision support scheme
      that could be used and adapted to various business decision processes. These
      involve decisions that are made under uncertain situations such as business
      competition in the market or wage negotiation within a firm. The scheme uses game
      strategies and fuzzy inference concepts to effectively grasp the variables in
      these uncertain situations. The games are played between human and fuzzy players.
      The accuracy of the fuzzy rule base and the game strategies help to mitigate the
      adverse effects that a business may suffer from these uncertain factors. We also
      introduced learning which enables the fuzzy player to adapt over time. We tested
      this scheme in different scenarios and discover that it could be an invaluable
      tool in the hand of entrepreneurs that are operating under uncertain and
      competitive business environments. 

PMID- 24109560
TI  - Integrating precision medicine in the study and clinical treatment of a severely
      mentally ill person.
AB  - Background. In recent years, there has been an explosion in the number of
      technical and medical diagnostic platforms being developed. This has greatly
      improved our ability to more accurately, and more comprehensively, explore and
      characterize human biological systems on the individual level. Large quantities
      of biomedical data are now being generated and archived in many separate research
      and clinical activities, but there exists a paucity of studies that integrate the
      areas of clinical neuropsychiatry, personal genomics and brain-machine
      interfaces. Methods. A single person with severe mental illness was implanted
      with the Medtronic Reclaim((r)) Deep Brain Stimulation (DBS) Therapy device for
      Obsessive Compulsive Disorder (OCD), targeting his nucleus accumbens/anterior
      limb of the internal capsule. Programming of the device and psychiatric
      assessments occurred in an outpatient setting for over two years. His genome was
      sequenced and variants were detected in the Illumina Whole Genome Sequencing
      Clinical Laboratory Improvement Amendments (CLIA)-certified laboratory. Results.
      We report here the detailed phenotypic characterization, clinical-grade whole
      genome sequencing (WGS), and two-year outcome of a man with severe OCD treated
      with DBS. Since implantation, this man has reported steady improvement,
      highlighted by a steady decline in his Yale-Brown Obsessive Compulsive Scale
      (YBOCS) score from ~38 to a score of ~25. A rechargeable Activa RC
      neurostimulator battery has been of major benefit in terms of facilitating a
      degree of stability and control over the stimulation. His psychiatric symptoms
      reliably worsen within hours of the battery becoming depleted, thus providing
      confirmatory evidence for the efficacy of DBS for OCD in this person. WGS
      revealed that he is a heterozygote for the p.Val66Met variant in BDNF, encoding a
      member of the nerve growth factor family, and which has been found to predispose
      carriers to various psychiatric illnesses. He carries the p.Glu429Ala allele in
      methylenetetrahydrofolate reductase (MTHFR) and the p.Asp7Asn allele in ChAT,
      encoding choline O-acetyltransferase, with both alleles having been shown to
      confer an elevated susceptibility to psychoses. We have found thousands of other
      variants in his genome, including pharmacogenetic and copy number variants. This
      information has been archived and offered to this person alongside the clinical
      sequencing data, so that he and others can re-analyze his genome for years to
      come. Conclusions. To our knowledge, this is the first study in the clinical
      neurosciences that integrates detailed neuropsychiatric phenotyping, deep brain
      stimulation for OCD and clinical-grade WGS with management of genetic results in
      the medical treatment of one person with severe mental illness. We offer this as
      an example of precision medicine in neuropsychiatry including brain-implantable
      devices and genomics-guided preventive health care. 

PMID- 24109563
TI  - The dilemma of the symbols: analogies between philosophy, biology and artificial
      life.
AB  - This article analyzes some analogies going from Artificial Life questions about
      the symbol-matter connection to Artificial Intelligence questions about symbol
      grounding. It focuses on the notion of the interpretability of syntax and how the
      symbols are integrated in a unity ("binding problem"). Utilizing the DNA code as
      a model, this paper discusses how syntactic features could be defined as high
      grade characteristics of the non syntactic relations in a material-dynamic
      structure, by using an emergentist approach. This topic furnishes the ground for
      a confutation of J. Searle's statement that syntax is observer-relative, as he
      wrote in his book "Mind: A Brief Introduction". Moreover the evolving discussion
      also modifies the classic symbol-processing doctrine in the mind which Searle
      attacks as a strong AL argument, that life could be implemented in a
      computational mode. Lastly, this paper furnishes a new way of support for the
      autonomous systems thesis in Artificial Life and Artificial Intelligence, using,
      inter alia, the "adaptive resonance theory" (ART). 

PMID- 24109564
TI  - Monoclonal antibody 10A5 recognizes an antigen unique to the water-insoluble
      25/45 membrane fraction of the rat ocular lens.
AB  - The water-insoluble 25/45 fraction and non-sedimenting membrane fraction (NSMF)
      are two membrane preparations isolated from the ocular lens. The fractions are
      postulated to represent distinct subdomains of the lens with unique functions.
      However, attempts to distinguish between the two fractions by detecting proteins
      present in one fraction but absent from other have been unsuccessful. In this
      study, we exploited the ability of the mouse immune system to detect antigenic
      differences between the 25/45 fraction and NSMF isolated from the lenses of 20
      day-old rats. We generated a monoclonal antibody (MAb 10A5) that reacts with a
      ganglioside-like antigen that is present in the 25/45 fraction but absent from
      the NSMF. Restriction of the antigen to the 25/45 fraction in 20-day-old animals
      supports the hypothesis that the 25/45 fraction and NSMF represent different
      subdomains within the ocular lens. 

PMID- 24109565
TI  - A systematic review and meta-analysis on the safety and efficacy of the frozen
      elephant trunk technique in aortic arch surgery.
AB  - BACKGROUND: The treatment of complex pathologies of the aortic arch and proximal
      descending aorta represents a significant challenge for cardiac surgeons. Various
      surgical techniques and prostheses have been implemented over the past several
      decades, all with varying degrees of success. The introduction of the frozen
      elephant trunk (FET) technique facilitates one-stage repair of such pathologies.
      The present systematic review and meta-analysis aims to assess the safety and
      efficacy of the FET approach in the current literature. METHODS: Electronic
      searches were performed using six databases from their inception to July 2013.
      Relevant studies utilizing the FET technique were identified. Data were extracted
      and analyzed according to predefined clinical endpoints. RESULTS: Seventeen
      studies were identified for inclusion for qualitative and quantitative analyses,
      all of which were observational reports. Pooled mortality was 8.3%, while stroke
      and spinal cord injuries were 4.9% and 5.1% respectively. Cardiopulmonary bypass
      time, myocardial ischemia time, and circulatory arrest time strongly correlated
      with perioperative mortality in a linear relationship, while moderate
      correlations between cerebral perfusion time and mortality, and circulatory
      arrest time and spinal cord injury, were also identified. Five-year survival,
      reported in five studies, ranged between 63-88%. CONCLUSIONS: Overall, results of
      the present systematic review and meta-analysis suggest that the FET procedure
      can be performed with acceptable mortality and morbidity risks.

PMID- 24109566
TI  - Aortic arch replacement with frozen elephant trunk-when not to use it.
AB  - Current scientific evidence suggests the frozen elephant trunk (FET) technique
      plays an important role in modern aortic arch repair operations, both for
      aneurysmal disease and acute aortic dissection. Its use in extended aneurysm is
      generally therapeutic, aiming for complete exclusion of the diseased descending
      thoracic aorta. In acute aortic dissection type A, the application of FET is more
      prophylactic in nature, with the aim of preventing late dilatation of the
      proximal descending thoracic aorta. This review will present the journey of the
      elephant trunk from its conception to the current available technology. By
      tracing the historical evolution of the FET technique and prosthesis development,
      we explore the challenges and limitations of evidence-based surgical research. We
      present data from our growing experience in aortic arch reconstruction, the
      results from our latest 27 patients undergoing the 4-branch FET indicating
      substantially reduced morbidity and mortality (0%) in this complex patient
      cohort. 

PMID- 24109567
TI  - Frozen elephant trunk surgery-the Bologna's experience.
AB  - BACKGROUND: Different approaches are available to treat patients with complex and
      extensive diseases of the thoracic aorta. This study aims to report and comment
      on our experience with the frozen elephant trunk (FET) technique. METHODS:
      Between January 2007 and July 2012, 122 patients (male: 86.9%; mean age: 61
      years) underwent extensive thoracic aorta surgery using the FET approach with an
      E-vita open prosthesis. The most frequent indications for surgery included
      residual type A chronic dissection (45.9%), extensive degenerative aneurysm of
      the thoracic aorta (27%), and type A acute aortic dissection (7.4%). Sixty-nine
      patients had already undergone cardiac/aortic interventions through a median
      sternotomy. A total of 60 associated procedures were performed, with 76.6% on the
      aortic root. Selective antegrade cerebral perfusion and moderate hypothermia were
      used in all cases. RESULTS: Overall, hospital mortality was 15.2%. Post
      operatively, 7.4% and 9.0% of patients were complicated by permanent neurologic
      dysfunction and spinal cord injury, respectively. For the surviving patients, 1-
      and 3-year freedom from all-cause mortality was (91.7+/-2.8)% and (79.1+/-6.1)%,
      respectively. 1- and 3-year freedom from re-intervention was (83.1+/-3.5)% and
      (74.1+/-4.3)%, respectively. CONCLUSIONS: In our experience, FET surgery allowed
      treatment of complex patients with extensive thoracic aortic diseases with
      satisfactory short- and mid-term results. Acute and chronic dissections represent
      interesting subsets for FET application. While further larger and longer-term
      studies are required to show the survival benefits of the FET technique versus
      other types of management, new strategies for spinal cord injury
      (paraplegia/paraparesis) reduction should also be researched.

PMID- 24109568
TI  - Early- and medium-term results after aortic arch replacement with frozen elephant
      trunk techniques-a single center study.
AB  - BACKGROUND: The treatment of patients with extensive thoracic aortic disease
      involving the arch and descending thoracic/thoracoabdominal aorta is often
      performed using the frozen elephant trunk technique (FET). We retrospectively
      analyzed our results of the FET operation. METHODS: A total of 51 consecutive
      patients underwent total aortic arch surgery with the FET technique between
      January 2006 and August 2013. For all patients, the E-vita hybrid open stent
      graft (Jotec, Hechingen, Germany) was used. The patients had a mean age of 64+/
      13 years, with 51.1% being female. Degenerative or atherosclerotic aneurysm was
      the indication for surgery in 62.7% of patients. Another 15.7% and 13.7% suffered
      from acute Type A, and Type B aortic dissection, respectively. RESULTS: The in
      hospital and 30-day mortality was 7.8%. Stroke occurred in 11.8% (n=6), and new
      onset paraplegia in 19.6% (n=10) of patients. The core body temperature >=28 
      degrees C during circulatory arrest, in combination with a prolonged circulatory
      arrest time of more than 45 minutes, was an independent predictor of permanent
      spinal cord injury [odds ratios (OR), 4.8; 95% confidence intervals (CI), 1.1-21;
      P=0.04]. The estimated 1- and 5-year survival was (80.2+/-5.5)% and (59.7+/
      10.2)%, respectively, with a mean survival time of 3.4+/-0.4 years. The estimated
      mean freedom from endovascular intervention was 4.2+/-0.4 years. The unadjusted 1
      and 5-year freedom from thoracic endovascular aortic repair (TEVAR) was (84.9+/
      5.9)% and (69.2+/-11.2)%, respectively. CONCLUSIONS: The FET procedure for
      extensive thoracic aortic disease is associated with an acceptable early and
      medium term mortality rate. This procedure is associated with a high incidence of
      perioperative spinal cord injury. In order to prevent the above complication,
      deep hypothermia is strongly recommended in patients with expected prolonged
      circulatory arrest time.

PMID- 24109569
TI  - Overall Essen's experience with the E-vita open hybrid stent graft system and
      evolution of the surgical technique.
AB  - BACKGROUND: The hybrid stent graft prosthesis E-vita open was designed and
      introduced by us in 2005 to avoid a two-stage surgical approach in the surgical
      treatment of complex thoracic aortic disease. Experience in ascending aortic and
      arch replacement with simultaneous stent grafting of the descending aorta was
      accumulated over the past 8 years. Facilitation of surgical technique by moving
      the distal suture line from Zone 3 into Zone 2 took place in 2009. We report our
      mid-term single-center experience comparing both surgical periods. METHODS:
      Between January 2005 and July 2013 a total of 132 patients (mean age 59+/-11
      years) underwent one stage surgery for acute (AAD, n=74), chronic aortic
      dissection (CAD, n=35) or an extensive thoracic aortic aneurysm (TAA, n=23).
      Patients were separated in two groups according to distal anastomosis level in
      Zone 2 (Z2, 41/132) and Zone 3 (Z3, 91/132). Outcome, ischemic and operative
      times as well as adverse events were monitored during follow up. RESULTS: Overall
      in-hospital mortality was 13% (17/132) without difference between the groups.
      However, Zone 2 anastomosis resulted in reduction of cardioplegic arrest (117+/
      39 vs. 147+/-35 minutes; P<0.001), selective cerebral perfusion (52+/-15 vs. 68+/
      18 minutes; P<0.001) and visceral ischemic time (51+/-19 vs. 72+/-23 minutes;
      P<0.001). The incidence of postoperative temporary hemodialysis decreased from
      40% to 20% in Z2 (P=0.028), postoperative re-exploration rate from 15% to 2%
      (P=0.037). No difference was found in dissection with complete false lumen
      thrombosis in 83% (90/109) within 10 days, as well as in TAA, where 100% aneurysm
      exclusion was observed. Three-year survival, freedom from thoracoabdominal aortic
      surgery and endovascular repair was 93%, 88%, 88%, respectively. Overall 5-year
      survival was 76% in AAD, 85% in CAD and 79% in TAA patients. CONCLUSIONS: The
      dimension of surgery could be successfully reduced, indicated by significantly
      shortened ischemic times and postoperative complications. Durable one-stage
      repair of complex thoracic aortic disease could be achieved in the majority of
      cases with acceptable mortality. Distal reintervention is infrequent but
      associated with low risk when indicated.

PMID- 24109571
TI  - The Sun procedure-a new paradigm of treatment in DeBakey type 1 acute aortic
      dissection?

PMID- 24109570
TI  - Sun's procedure of total arch replacement using a tetrafurcated graft with
      stented elephant trunk implantation: analysis of early outcome in 398 patients
      with acute type A aortic dissection.
AB  - BACKGROUND: Acute type A aortic dissection (AAAD) remains one of the most lethal
      conditions requiring surgical repair, and is associated with a high rate of
      postoperative mortality and morbidity. Despite the satisfactory clinical outcomes
      achieved with the frozen elephant trunk technique so far, controversies still
      exist regarding the use of this aggressive approach in patients with AAAD. In
      this study, we seek to analyze the early outcomes of the Sun's procedure, which
      is an approach integrating total arch replacement using a 4-branched graft with
      implantation of a special stented graft in the descending aorta, and identify the
      risk factors for postoperative mortality and morbidity of the Sun's procedure in
      patients with AAAD. METHODS: Clinical data of 398 consecutive AAAD patients
      undergoing the Sun's procedure were analyzed. The associations between 20
      preoperative and intraoperative variables and early mortality were assessed by
      univariate and multivariate analysis. RESULTS: Early mortality occurred in 31
      patients (7.8%, 31/398), with leading causes including multi-organ failure in 16
      patients (51.6%), permanent neurologic deficit in 6 (19.4%), and low cardiac
      output syndrome in 4 (12.9%). Permanent neurologic deficit and spinal cord injury
      occurred, each in 10 patients (2.5%, 10/398). Five significant risk factors for
      early mortality were identified with multivariate analysis: preexisting
      cerebrovascular disease [relative risk (RR) 14.76; P<0.001], acute heart failure
      (RR 18.18; P=0.001), spinal cord malperfusion (RR 60.13; P<0.002), visceral
      malperfusion (RR 30.25; P<0.001) and cardiopulmonary bypass time >190 minutes (RR
      3.62; P=0.007). CONCLUSIONS: The Sun's procedure has generated a relatively lower
      mortality rate in 398 patients with AAAD. Patients with preexisting
      cerebrovascular disease, acute heart failure, spinal cord malperfusion, visceral
      malperfusion and long cardiopulmonary bypass time are at a higher risk of early
      mortality.

PMID- 24109572
TI  - Importance of entry tears in Type B aortic dissection prognosis.

PMID- 24109573
TI  - Trade in the hammer for a power driver-perspectives on the frozen elephant trunk
      repair for aortic arch disease.
AB  - Like a power driver for which the bit can be changed for each screw that is
      turned, improvement of brain protection strategies and the development of hybrid
      techniques have provided us with the ability to offer tailored repair options for
      patients with complex thoracic disease involving the arch. Variations of the
      frozen elephant trunk operation have been the most versatile of the newer hybrid
      approaches to repair complex thoracic aortic pathology. The frozen elephant trunk
      procedure includes the use of circulatory arrest in combination with suturing a
      stentgraft into the arch, and may reduce the risk of stroke and endoleaks. This
      article describes various methods of performing the frozen elephant trunk
      procedure with a focus on preoperative considerations including the etiology of
      disease, the time and urgency of presentation, and the indications to operate. 

PMID- 24109574
TI  - Frozen elephant trunk in acute type I dissection-a personal view.

PMID- 24109575
TI  - Sun's procedure for complex aortic arch repair: total arch replacement using a
      tetrafurcate graft with stented elephant trunk implantation.
AB  - The Sun's procedure is a surgical technique proposed by Dr. Li-Zhong Sun in 2002
      that integrates total aortic arch replacement using a tetrafurcated graft with
      implantation of a specially designed frozen elephant trunk (Cronus((r))) in the
      descending aorta. It is used as a treatment option for extensive aortic
      dissections or aneurysms involving the ascending aorta, aortic arch and the
      descending aorta. The technical essentials of Sun's procedure include
      implantation of the special open stented graft into the descending aorta, total
      arch replacement with a 4-branched vascular graft, right axillary artery
      cannulation, selective antegrade cerebral perfusion for brain protection,
      moderate hypothermic circulatory arrest at 25  degrees C, a special anastomotic
      sequence for aortic reconstruction (i.e., proximal descending aorta -> left
      carotid artery -> ascending aorta -> left subclavian artery -> innominate
      artery), and early rewarming and reperfusion after distal anastomosis to minimize
      cerebral and cardiac ischemia. The core advantage of Sun's procedure lies in the
      use of a unique stented graft, which has superior technical simplicity,
      flexibility, inherent mechanical durability and an extra centimeter of attached
      regular vascular graft at both ends. Since its introduction in 2003, the Sun's
      procedure has produced satisfactory early and long-term results in over 8,000
      patients in China and more than 200 patients in South American countries. In a
      series of 1,092 patients, the authors have achieved an in-hospital mortality rate
      of 6.27% (7.98% in emergent or urgent vs. 3.98% in elective cases). Given the
      accumulating clinical experience and the consequent, continual evolution of
      surgical indications, the Sun's procedure is becoming increasingly applied/used
      worldwide as an innovative and imaginative enhancement of surgical options for
      the dissected (or aneurysmal) ascending aorta, aortic arch and proximal
      descending aorta, and may become the next standard treatment for type A aortic
      dissections requiring repair of the aortic arch. 

PMID- 24109577
TI  - Angioscopy as a supplement to frozen elephant trunk treatment.

PMID- 24109576
TI  - Total arch replacement with frozen elephant trunk technique.

PMID- 24109578
TI  - Frozen elephant trunk surgery using the E-vita open plus prosthesis.

PMID- 24109579
TI  - Frozen elephant trunk surgery using the Vascutek Thora-flex hybrid prosthesis.

PMID- 24109580
TI  - Facilitated surgical strategy in total arch replacement and descending aorta
      stent grafting with the E-vita open hybrid prosthesis.

PMID- 24109581
TI  - Sun's procedure for chronic type A aortic dissection: total arch replacement
      using a tetrafurcate graft with stented elephant trunk implantation.

PMID- 24109582
TI  - Aortic root and total arch replacement with frozen elephant trunk procedure,
      using a Thoraflex Hybrid Graft.

PMID- 24109583
TI  - Safety and pitfalls in frozen elephant trunk implantation.
AB  - The frozen elephant trunk (FET) procedure, or open stent grafting, is a tool for
      the combined open and endovascular treatment via a median sternotomy of extensive
      aortic disease involving both aortic arch and descending thoracic aorta. The
      technique aims to stabilize the maximum extent of the thoracic aorta in one step,
      with the goal of either rendering a secondary intervention to the downstream
      aorta unnecessary or producing an easy landing zone for secondary thoracic
      endovascular aortic repair (TEVAR) or open surgery. Even though large case series
      have reported good results, we still have no conclusive evidence as to which
      patients and what kind of pathologies benefit from this technique. The surgical
      sequences described for total arch replacement with the FET procedure are just as
      varied as the associated devices and indications. This article focuses on
      important perioperative and surgical aspects, as well as potential complications
      during FET procedures. 

PMID- 24109584
TI  - Systematic review protocol: single-dose histidine-tryptophan-ketoglutarate vs.
      intermittent crystalloid or blood cardioplegia.

PMID- 24109585
TI  - Systematic review protocol: robotically-assisted minimally invasive mitral valve
      surgery.

PMID- 24109587
TI  - Hybrid aortic arch surgery.

PMID- 24109586
TI  - Meta-analysis protocol: MitraClip system versus surgery for treatment of severe
      mitral regurgitation.

PMID- 24109589
TI  - Why Healthcare Providers Should Focus on the Fertility of AYA Cancer Survivors:
      It's Not Too Late!
AB  - Reproductive health among cancer survivors is an important quality of life issue.
      Certain cancer therapies have known fertility risks. There is an existing cohort
      of adolescents and young adults (AYA) cancer survivors that, seen less frequently
      in clinical care settings than active patients, are likely not having discussions
      of fertility and other reproductive health issues. A survivor or healthcare
      provider can easily assume that the window of opportunity for fertility
      preservation has passed, however emerging research has shown this may not be the
      case. Recent data demonstrates a close relationship between fertility and other
      late effects to conclude that ongoing assessment during survivorship is
      warranted. Some fertility preservation procedures have also been shown to
      mitigate common late effects. This review explores the link between late effects
      from treatment and common comorbidities from infertility, which may exacerbate
      these late effects. This review also highlights the relevance of fertility
      discussions in the AYA survivorship population. 

PMID- 24109588
TI  - Implications of Rho GTPase Signaling in Glioma Cell Invasion and Tumor
      Progression.
AB  - Glioblastoma (GB) is the most malignant of primary adult brain tumors,
      characterized by a highly locally invasive cell population, as well as abundant
      proliferative cells, neoangiogenesis, and necrosis. Clinical intervention with
      chemotherapy or radiation may either promote or establish an environment for
      manifestation of invasive behavior. Understanding the molecular drivers of
      invasion in the context of glioma progression may be insightful in directing new
      treatments for patients with GB. Here, we review current knowledge on Rho family
      GTPases, their aberrant regulation in GB, and their effect on GB cell invasion
      and tumor progression. Rho GTPases are modulators of cell migration through
      effects on actin cytoskeleton rearrangement; in non-neoplastic tissue, expression
      and activation of Rho GTPases are normally under tight regulation. In GB, Rho
      GTPases are deregulated, often via hyperactivity or overexpression of their
      activators, Rho GEFs. Downstream effectors of Rho GTPases have been shown to
      promote invasiveness and, importantly, glioma cell survival. The study of
      aberrant Rho GTPase signaling in GB is thus an important investigation of cell
      invasion as well as treatment resistance and disease progression. 

PMID- 24109590
TI  - Tumor regression grading of gastrointestinal carcinomas after neoadjuvant
      treatment.
AB  - Multimodal therapy concepts have been successfully implemented in the treatment
      of locally advanced gastrointestinal malignancies. The effects of neoadjuvant
      chemo- or radiochemotherapy such as scarry fibrosis or resorptive changes and
      inflammation can be determined by histopathological investigation of the
      subsequent resection specimen. Tumor regression grading (TRG) systems which aim
      to categorize the amount of regressive changes after cytotoxic treatment mostly
      refer onto the amount of therapy induced fibrosis in relation to residual tumor
      or the estimated percentage of residual tumor in relation to the previous tumor
      site. Commonly used TRGs for upper gastrointestinal carcinomas are the Mandard
      grading and the Becker grading system, e.g., and for rectal cancer the Dworak or
      the Rodel grading system, or other systems which follow similar definitions.
      Namely for gastro-esophageal carcinomas these TRGs provide important prognostic
      information since complete or subtotal tumor regression has shown to be
      associated with better patient's outcome. The prognostic value of TRG may even
      exceed those of currently used staging systems (e.g., TNM staging) for tumors
      treated by neoadjuvant therapy. There have been some limitations described
      regarding interobserver variability especially in borderline cases, which may be
      improved by standardization of work up of resection specimen and better training
      of histopathologic determination of regressive changes. It is highly recommended
      that TRG should be implemented in every histopathological report of neoadjuvant
      treated gastrointestinal carcinomas. The aim of this review is to disclose the
      relevance of histomorphological TRG to accomplish an optimal therapy for patients
      with gastrointestinal carcinomas. 

PMID- 24109591
TI  - The Role of Bystander Effects in the Antitumor Activity of the Hypoxia-Activated
      Prodrug PR-104.
AB  - Activation of prodrugs in tumors (e.g., by bioreduction in hypoxic zones) has the
      potential to generate active metabolites that can diffuse within the tumor
      microenvironment. Such "bystander effects" may offset spatial heterogeneity in
      prodrug activation but the relative importance of this effect is not understood.
      Here, we quantify the contribution of bystander effects to antitumor activity for
      the first time, by developing a spatially resolved
      pharmacokinetic/pharmacodynamic (SR-PK/PD) model for PR-104, a phosphate ester
      pre-prodrug that is converted systemically to the hypoxia-activated prodrug PR
      104A. Using Green's function methods we calculated concentrations of oxygen, PR
      104A and its active metabolites, and resultant cell killing, at each point of a
      mapped three-dimensional tumor microregion. Model parameters were determined in
      vitro, using single cell suspensions to determine relationships between PR-104A
      metabolism and clonogenic cell killing, and multicellular layer (MCL) cultures to
      measure tissue diffusion coefficients. LC-MS/MS detection of active metabolites
      in the extracellular medium following exposure of anoxic single cell suspensions
      and MCLs to PR-104A confirmed that metabolites can diffuse out of cells and
      through a tissue-like environment. The SR-PK/PD model estimated that bystander
      effects contribute 30 and 50% of PR-104 activity in SiHa and HCT116 tumors,
      respectively. Testing the model by modulating PR-104A-activating reductases and
      hypoxia in tumor xenografts showed overall clonogenic killing broadly consistent
      with model predictions. Overall, our data suggest that bystander effects are
      important in PR-104 antitumor activity, although their reach may be limited by
      macroregional heterogeneity in hypoxia and reductase expression in tumors. The
      reported computational and experimental techniques are broadly applicable to all
      targeted anticancer prodrugs and could be used to identify strategies for
      rational prodrug optimization. 

PMID- 24109592
TI  - Host specialization in ticks and transmission of tick-borne diseases: a review.
AB  - Determining patterns of host use, and the frequency at which these patterns
      change, are of key importance if we are to understand tick population dynamics,
      the evolution of tick biodiversity, and the circulation and evolution of
      associated pathogens. The question of whether ticks are typically host
      specialists or host generalists has been subject to much debate over the last
      half-century. Indeed, early research proposed that morphological diversity in
      ticks was linked to host specific adaptations and that most ticks were
      specialists. Later work disputed this idea and suggested that ticks are largely
      limited by biogeographic conditions and tend to use all locally available host
      species. The work presented in this review suggests that the actual answer likely
      lies somewhere between these two extremes. Although recent observational studies
      support the view that phylogenetically diverse host species share ticks when
      found on similar ecological ranges, theory on host range evolution predicts that
      host specialization should evolve in ticks given their life history
      characteristics. Contemporary work employing population genetic tools to examine
      host-associated population structure in several tick systems support this
      prediction and show that simple species records are not enough to determine
      whether a parasite is a true host generalist; host specialization does evolve in
      ticks at local scales, but may not always lead to speciation. Ticks therefore
      seem to follow a pattern of being global generalists, local specialists. Given
      this, the notion of host range needs to be modified from an evolutionary
      perspective, where one simply counts the number of hosts used across the
      geographic distribution, to a more ecological view, where one considers host use
      at a local scale, if we are to better understand the circulation of tick-borne
      pathogens and exposure risks for humans and livestock. 

PMID- 24109593
TI  - Hepatic-specific accessibility of Igf1 gene enhancers is independent of growth
      hormone signaling.
AB  - The diverse roles of IGF-1 in physiology include acting as the endocrine
      intermediate to elicit the anabolic actions of GH. The majority of serum IGF-1 is
      synthesized in liver, where GH stimulates Igf1 gene transcription via the
      transcription factor, signal transducer and activator of transcription (Stat)5b.
      We and others have identified multiple Stat5-binding domains at the Igf1 locus
      that function in gene regulation, but it remains unclear whether the roles of
      these domains are tissue specific. Survey of the chromatin landscape of
      regulatory domains can provide insight about mechanisms of gene regulation, with
      chromatin accessibility regarded as a hallmark feature of regulatory domains. We
      prepared chromatin from liver, kidney, and spleen of C57BL/6 mice, and used
      formaldehyde-associated isolation of regulatory elements to assess chromatin
      accessibility at the major Igf1 promoter and 7 -binding enhancers. Whereas the
      promoters of other prototypical tissue-specific genes are open in a tissue
      specific way, the major Igf1 promoter is open in all 3 tissues, albeit moderately
      more so in liver. In contrast, chromatin accessibility at Igf1 Stat5-binding
      domains is essentially restricted to liver, indicating that the enhancers are
      driving extensive differences in tissue expression. Furthermore, studies with
      Ghrhr(lit/lit) mice reveal that prior GH exposure is not necessary to establish
      open chromatin at these domains. Lastly, formaldehyde-associated isolation of
      regulatory elements of human liver samples confirms open chromatin at IGF1
      Promoter 1, but unexpectedly, homologous Stat5-binding motifs are not accessible.
      We conclude that robust GH-stimulated hepatic Igf1 gene transcription utilizes
      tissue-specific mechanisms of epigenetic regulation that are established
      independent of GH signaling. 

PMID- 24109595
TI  - Two potentially novel amylolytic enzyme specificities in the prokaryotic
      glycoside hydrolase alpha-amylase family GH57.
AB  - Glycoside hydrolase (GH) family 57 consists of more than 900 proteins from
      Archaea (roughly one-quarter) and Bacteria (roughly three-quarters), mostly from
      thermophiles. Fewer than 20 GH57 members have already been biochemically
      characterized as real, (almost exclusively) amylolytic enzymes. In addition to a
      recently described dual-specificity amylopullulanase-cyclomaltodextrinase, five
      enzyme specificities have been well established in the family--alpha-amylase,
      amylopullulanase, branching enzyme, 4-alpha-glucanotransferase and alpha
      galactosidase--plus a group of the so-called alpha-amylase-like homologues
      probably without the enzyme activity. A (beta/alpha)7-barrel succeeded by a
      bundle of a few alpha-helices forming the catalytic domain, and five conserved
      sequence regions (CSRs), are the main characteristics of family GH57. The main
      goal of the present bioinformatics study was to describe two novel groups within
      family GH57 that represent potential non-specified amylases (127 sequences mostly
      from Bacteria) and maltogenic amylases (12 sequences from Archaea). These were
      collected from sequence databases based on an indication of their biochemical
      characterization. Although both the non-specified amylases and the maltogenic
      amylases share the in silico identified catalytic machinery and predicted fold
      with the experimentally determined GH57 members, the two novel groups may define
      new GH57 subfamilies. They are distinguishable from the other, previously
      recognized, subfamilies by specific sequence features present especially in their
      CSRs (the so-called sequence fingerprints), also reflecting their own
      evolutionary histories.

PMID- 24109594
TI  - Androgen regulation of the TMPRSS2 gene and the effect of a SNP in an androgen
      response element.
AB  - More than 50% of prostate cancers have undergone a genomic reorganization that
      juxtaposes the androgen-regulated promoter of TMPRSS2 and the protein coding
      parts of several ETS oncogenes. These gene fusions lead to prostate-specific and
      androgen-induced ETS expression and are associated with aggressive lesions, poor
      prognosis, and early-onset prostate cancer. In this study, we showed that an
      enhancer at 13 kb upstream of the TMPRSS2 transcription start site is crucial for
      the androgen regulation of the TMPRSS2 gene when tested in bacterial artificial
      chromosomal vectors. Within this enhancer, we identified the exact androgen
      receptor binding sequence. This newly identified androgen response element is
      situated next to two binding sites for the pioneer factor GATA2, which were
      identified by DNase I footprinting. Both the androgen response element and the
      GATA-2 binding sites are involved in the enhancer activity. Importantly, a single
      nucleotide polymorphism (rs8134378) within this androgen response element reduces
      binding and transactivation by the androgen receptor. The presence of this SNP
      might have implications on the expression and/or formation levels of TMPRSS2
      fusions, because both have been shown to be influenced by androgens. 

PMID- 24109596
TI  - Syntaxin 16 is a master recruitment factor for cytokinesis.
AB  - Recently it was shown that both recycling endosome and endosomal sorting complex
      required for transport (ESCRT) components are required for cytokinesis, in which
      they are believed to act in a sequential manner to bring about secondary
      ingression and abscission, respectively. However, it is not clear how either of
      these complexes is targeted to the midbody and whether their delivery is
      coordinated. The trafficking of membrane vesicles between different intracellular
      organelles involves the formation of soluble N-ethylmaleimide-sensitive factor
      attachment protein receptor (SNARE) complexes. Although membrane traffic is known
      to play an important role in cytokinesis, the contribution and identity of
      intracellular SNAREs to cytokinesis remain unclear. Here we demonstrate that
      syntaxin 16 is a key regulator of cytokinesis, as it is required for recruitment
      of both recycling endosome-associated Exocyst and ESCRT machinery during late
      telophase, and therefore that these two distinct facets of cytokinesis are
      inextricably linked.

PMID- 24109597
TI  - Identification of cell cycle-regulated genes periodically expressed in U2OS cells
      and their regulation by FOXM1 and E2F transcription factors.
AB  - We identify the cell cycle-regulated mRNA transcripts genome-wide in the
      osteosarcoma-derived U2OS cell line. This results in 2140 transcripts mapping to
      1871 unique cell cycle-regulated genes that show periodic oscillations across
      multiple synchronous cell cycles. We identify genomic loci bound by the G2/M
      transcription factor FOXM1 by chromatin immunoprecipitation followed by high
      throughput sequencing (ChIP-seq) and associate these with cell cycle-regulated
      genes. FOXM1 is bound to cell cycle-regulated genes with peak expression in both
      S phase and G2/M phases. We show that ChIP-seq genomic loci are responsive to
      FOXM1 using a real-time luciferase assay in live cells, showing that FOXM1
      strongly activates promoters of G2/M phase genes and weakly activates those
      induced in S phase. Analysis of ChIP-seq data from a panel of cell cycle
      transcription factors (E2F1, E2F4, E2F6, and GABPA) from the Encyclopedia of DNA
      Elements and ChIP-seq data for the DREAM complex finds that a set of core cell
      cycle genes regulated in both U2OS and HeLa cells are bound by multiple cell
      cycle transcription factors. These data identify the cell cycle-regulated genes
      in a second cancer-derived cell line and provide a comprehensive picture of the
      transcriptional regulatory systems controlling periodic gene expression in the
      human cell division cycle. 

PMID- 24109598
TI  - NuMA localization, stability, and function in spindle orientation involve 4.1 and
      Cdk1 interactions.
AB  - The epidermis is a multilayered epithelium that requires asymmetric divisions for
      stratification. A conserved cortical protein complex, including LGN, nuclear
      mitotic apparatus (NuMA), and dynein/dynactin, plays a key role in establishing
      proper spindle orientation during asymmetric divisions. The requirements for the
      cortical recruitment of these proteins, however, remain unclear. In this work, we
      show that NuMA is required to recruit dynactin to the cell cortex of
      keratinocytes. NuMA's cortical recruitment requires LGN; however, LGN
      interactions are not sufficient for this localization. Using fluorescence
      recovery after photobleaching, we find that the 4.1-binding domain of NuMA is
      important for stabilizing its interaction with the cell cortex. This is
      functionally important, as loss of 4.1/NuMA interaction results in spindle
      orientation defects, using two distinct assays. Furthermore, we observe an
      increase in cortical NuMA localization as cells enter anaphase. Inhibition of
      Cdk1 or mutation of a single residue in NuMA mimics this effect. NuMA's anaphase
      localization is independent of LGN and 4.1 interactions, revealing two distinct
      mechanisms responsible for NuMA cortical recruitment at different stages of
      mitosis. This work highlights the complexity of NuMA localization and reveals the
      importance of NuMA cortical stability for productive force generation during
      spindle orientation. 

PMID- 24109599
TI  - Repressed synthesis of ribosomal proteins generates protein-specific cell cycle
      and morphological phenotypes.
AB  - The biogenesis of ribosomes is coordinated with cell growth and proliferation.
      Distortion of the coordinated synthesis of ribosomal components affects not only
      ribosome formation, but also cell fate. However, the connection between ribosome
      biogenesis and cell fate is not well understood. To establish a model system for
      inquiries into these processes, we systematically analyzed cell cycle
      progression, cell morphology, and bud site selection after repression of 54
      individual ribosomal protein (r-protein) genes in Saccharomyces cerevisiae. We
      found that repression of nine 60S r-protein genes results in arrest in the G2/M
      phase, whereas repression of nine other 60S and 22 40S r-protein genes causes
      arrest in the G1 phase. Furthermore, bud morphology changes after repression of
      some r-protein genes. For example, very elongated buds form after repression of
      seven 60S r-protein genes. These genes overlap with, but are not identical to,
      those causing the G2/M cell cycle phenotype. Finally, repression of most r
      protein genes results in changed sites of bud formation. Strikingly, the r
      proteins whose repression generates similar effects on cell cycle progression
      cluster in the ribosome physical structure, suggesting that different topological
      areas of the precursor and/or mature ribosome are mechanistically connected to
      separate aspects of the cell cycle. 

PMID- 24109600
TI  - The Hsp70/90 cochaperone, Sti1, suppresses proteotoxicity by regulating spatial
      quality control of amyloid-like proteins.
AB  - Conformational diseases are associated with the conversion of normal proteins
      into aggregation-prone toxic conformers with structures similar to that of beta
      amyloid. Spatial distribution of amyloid-like proteins into intracellular quality
      control centers can be beneficial, but cellular mechanisms for protective
      aggregation remain unclear. We used a high-copy suppressor screen in yeast to
      identify roles for the Hsp70 system in spatial organization of toxic
      polyglutamine-expanded Huntingtin (Huntingtin with 103Q glutamine stretch
      [Htt103Q]) into benign assemblies. Under toxic conditions, Htt103Q accumulates in
      unassembled states and speckled cytosolic foci. Subtle modulation of Sti1
      activity reciprocally affects Htt toxicity and the packaging of Htt103Q into
      foci. Loss of Sti1 exacerbates Htt toxicity and hinders foci formation, whereas
      elevation of Sti1 suppresses Htt toxicity while organizing small Htt103Q foci
      into larger assemblies. Sti1 also suppresses cytotoxicity of the glutamine-rich
      yeast prion [RNQ+] while reorganizing speckled Rnq1-monomeric red fluorescent
      protein into distinct foci. Sti1-inducible foci are perinuclear and contain
      proteins that are bound by the amyloid indicator dye thioflavin-T. Sti1 is an
      Hsp70 cochaperone that regulates the spatial organization of amyloid-like
      proteins in the cytosol and thereby buffers proteotoxicity caused by amyloid-like
      proteins. 

PMID- 24109601
TI  - Site-specific structural constraints on protein sequence evolutionary divergence:
      local packing density versus solvent exposure.
AB  - Protein sequences evolve under selection pressures imposed by functional and
      biophysical requirements, resulting in site-dependent rates of amino acid
      substitution. Relative solvent accessibility (RSA) and local packing density
      (LPD) have emerged as the best candidates to quantify structural constraint.
      Recent research assumes that RSA is the main determinant of sequence divergence.
      However, it is not yet clear which is the best predictor of substitution rates.
      To address this issue, we compared RSA and LPD with site-specific rates of
      evolution for a diverse data set of enzymes. In contrast with recent studies, we
      found that LPD measures correlate better than RSA with evolutionary rate.
      Moreover, the independent contribution of RSA is minor. Taking into account that
      LPD is related to backbone flexibility, we put forward the possibility that the
      rate of evolution of a site is determined by the ease with which the backbone
      deforms to accommodate mutations. 

PMID- 24109602
TI  - Ancient origins of vertebrate-specific innate antiviral immunity.
AB  - Animals deploy various molecular sensors to detect pathogen infections. RIG-like
      receptor (RLR) proteins identify viral RNAs and initiate innate immune responses.
      The three human RLRs recognize different types of RNA molecules and protect
      against different viral pathogens. The RLR protein family is widely thought to
      have originated shortly before the emergence of vertebrates and rapidly
      diversified through a complex process of domain grafting. Contrary to these
      findings, here we show that full-length RLRs and their downstream signaling
      molecules were present in the earliest animals, suggesting that the RLR-based
      immune system arose with the emergence of multicellularity. Functional
      differentiation of RLRs occurred early in animal evolution via simple gene
      duplication followed by modifications of the RNA-binding pocket, many of which
      may have been adaptively driven. Functional analysis of human and ancestral RLRs
      revealed that the ancestral RLR displayed RIG-1-like RNA-binding. MDA5-like
      binding arose through changes in the RNA-binding pocket following the duplication
      of the ancestral RLR, which may have occurred either early in Bilateria or later,
      after deuterostomes split from protostomes. The sensitivity and specificity with
      which RLRs bind different RNA structures has repeatedly adapted throughout
      mammalian evolution, suggesting a long-term evolutionary arms race with viral RNA
      or other molecules. 

PMID- 24109603
TI  - Chorion patterning: a window into gene regulation and Drosophila species'
      relatedness.
AB  - Changes in gene regulation are associated with the evolution of morphologies.
      However, the specific sequence information controlling gene expression is largely
      unknown and discovery is time and labor consuming. We use the intricate
      patterning of follicle cells to probe species' relatedness in the absence of
      sequence information. We focus on one of the major families of genes that pattern
      the Drosophila eggshell, the Chorion protein (Cp). Systematically screening for
      the spatiotemporal patterning of all nine Cp genes in three species (Drosophila
      melanogaster, D. nebulosa, and D. willistoni), we found that most genes are
      expressed dynamically during mid and late stages of oogenesis. Applying an
      annotation code, we transformed the data into binary matrices that capture the
      complexity of gene expression. Gene patterning is sufficient to predict species'
      relatedness, consistent with their phylogeny. Surprisingly, we found that
      expression domains of most genes are different among species, suggesting that Cp
      regulation is rapidly evolving. In addition, we found a morphological novelty
      along the dorsalmost side of the eggshell, the dorsal ridge. Our matrix analysis
      placed the dorsal ridge domain in a cluster of epidermal growth factor receptor
      associated domains, which was validated through genetic and chemical
      perturbations. Expression domains are regulated cooperatively or independently by
      signaling pathways, supporting that complex patterns are combinatorially
      assembled from simple domains. 

PMID- 24109610
TI  - Reconstruction and analysis of the pupil dilation signal: Application to a
      psychophysiological affective protocol.
AB  - Pupil dilation (PD) dynamics reflect the interactions of sympathetic and
      parasympathetic innervations in the iris muscle. Different pupillary responses
      have been observed with respect to emotionally characterized stimuli. Evidences
      of the correlation between PD and respiration, heart rate variability (HRV) and
      blood pressure (BP) are present in literature, making the pupil dilation a
      candidate for estimating the activity state of the Autonomic Nervous System
      (ANS), in particular during stressful and/or emotionally characterized stimuli.
      The aim of this study is to investigate whether both slow and fast PD dynamics
      can be addressed to characterized different affective states. Two different
      frequency bands were considered: the classical autonomic band [0-0.45] Hz and a
      very high frequency (VHF) band [0.45-5] Hz. The pupil dilation signals from 13
      normal subjects were recorded during a psychological protocol suitable to evoke
      particular affective states. An elaborate reconstruction of the missing data
      (blink events and artifacts) was performed to obtain a more reliable signal,
      particularly in the VHF band. Results show a high correlation between the arousal
      of the event and the power characteristics of the signal, in all frequencies. In
      particular, for the "Anger" condition, we can observe 10 indices out of 13
      significantly different with respect to "Baseline" counterparts. These
      preliminary results suggest that both slow and fast oscillations of the PD can be
      used to characterize affective states. 

PMID- 24109604
TI  - Experimental evolution of pseudogenization and gene loss in a plant RNA virus.
AB  - Viruses have evolved highly streamlined genomes and a variety of mechanisms to
      compress them, suggesting that genome size is under strong selection. Horizontal
      gene transfer has, on the other hand, played an important role in virus
      evolution. However, evolution cannot integrate initially nonfunctional sequences
      into the viral genome if they are rapidly purged by selection. Here we report on
      the experimental evolution of pseudogenization in virus genomes using a plant RNA
      virus expressing a heterologous gene. When long 9-week passages were performed,
      the added gene was lost in all lineages, whereas viruses with large genomic
      deletions were fixed in only two out of ten 3-week lineages and none in 1-week
      lineages. Illumina next-generation sequencing revealed considerable convergent
      evolution in the 9- and 3-week lineages with genomic deletions. Genome size was
      correlated to within-host competitive fitness, although there was no correlation
      with virus accumulation or virulence. Within-host competitive fitness of the 3
      week virus lineages without genomic deletions was higher than for the 1-week
      lineages. Our results show that the strength of selection for a reduced genome
      size and the rate of pseudogenization depend on demographic conditions. Moreover,
      for the 3-week passage condition, we observed increases in within-host fitness,
      whereas selection was not strong enough to quickly remove the nonfunctional
      heterologous gene. These results suggest a demographically determined "sweet
      spot" might exist, where heterologous insertions are not immediately lost while
      evolution can act to integrate them into the viral genome. 

PMID- 24109611
TI  - Adaptive sensing of ECG signals using R-R interval prediction.
AB  - There is growing demand for systems consisting of tiny sensor nodes powered with
      small batteries that acquire electrocardiogram (ECG) data and wirelessly transmit
      the data to remote base stations or mobile phones continuously over a long
      period. Conserving electric power in the wireless sensor nodes (WSNs) is
      essential in such systems. Adaptive sensing is promising for this purpose since
      it can reduce the energy consumed not only for data transmission but also for
      sensing. However, the basic method of adaptive sensing, referred to here as
      "plain adaptive sensing," is not suitable for ECG signals because it sometimes
      capture the R waves defectively. We introduce an improved adaptive sensing method
      for ECG signals by incorporating R-R interval prediction. Our method improves the
      characteristics of ECG compression and drastically reduces the total energy
      consumption of the WSNs. 

PMID- 24109612
TI  - Real time eye blink noise removal from EEG signals using morphological component
      analysis.
AB  - This paper presents a method of removing the noise caused by eye blinks from an
      electroencephalogram (EEG) signal in real time based on morphological component
      analysis (MCA). This method sparsely represents both the eye blink and the EEG
      signal basis matrices using a Short Time Fourier Transform (STFT). This approach
      has two main advantages: 1) fast computation of the estimation of the signal
      coefficients using the basis pursuit algorithm 2) less memory requirement. The
      obtained result shows that the correlation coefficient between the raw EEG and
      the cleaned EEG is between 0.72 and 0.94 which implies that it is possible to
      remove eye blink noise from the EEG signal in real time without affecting an
      underlying brain signal. 

PMID- 24109613
TI  - Multiple sensor integration for seizure onset detection in human patients
      comparing conventional disc versus novel tripolar concentric ring electrodes.
AB  - As epilepsy affects approximately one percent of the world population, electrical
      stimulation of the brain has recently shown potential for additive seizure
      control therapy. Closed-loop systems that apply electrical stimulation when
      seizure onset is automatically detected require high accuracy of automatic
      seizure detection based on electrographic brain activity. To improve this
      accuracy we propose to use noninvasive tripolar concentric ring electrodes that
      have been shown to have significantly better signal-to-noise ratio, spatial
      selectivity, and mutual information compared to conventional disc electrodes. The
      proposed detection methodology is based on integration of multiple sensors using
      exponentially embedded family (EEF). In this preliminary study it is validated on
      over 26.3 hours of data collected using both tripolar concentric ring and
      conventional disc electrodes concurrently each from 7 human patients with
      epilepsy including five seizures. For a cross-validation based group model EEF
      correctly detected 100% and 80% of seizures respectively with <0.76 and <1.56
      false positive detections per hour respectively for the two electrode modalities.
      These results clearly suggest the potential of seizure onset detection based on
      data from tripolar concentric ring electrodes. 

PMID- 24109614
TI  - Human joint motion estimation for electromyography (EMG)-based dynamic motion
      control.
AB  - This study aims to investigate a joint motion estimation method from
      Electromyography (EMG) signals during dynamic movement. In most EMG-based
      humanoid or prosthetics control systems, EMG features were directly or indirectly
      used to trigger intended motions. However, both physiological and
      nonphysiological factors can influence EMG characteristics during dynamic
      movements, resulting in subject-specific, non-stationary and crosstalk problems.
      Particularly, when motion velocity and/or joint torque are not constrained, joint
      motion estimation from EMG signals are more challenging. In this paper, we
      propose a joint motion estimation method based on muscle activation recorded from
      a pair of agonist and antagonist muscles of the joint. A linear state-space model
      with multi input single output is proposed to map the muscle activity to joint
      motion. An adaptive estimation method is proposed to train the model. The
      estimation performance is evaluated in performing a single elbow flexion
      extension movement in two subjects. All the results in two subjects at two load
      levels indicate the feasibility and suitability of the proposed method in joint
      motion estimation. The estimation root-mean-square error is within 8.3% ~ 10.6%,
      which is lower than that being reported in several previous studies. Moreover,
      this method is able to overcome subject-specific problem and compensate non
      stationary EMG properties. 

PMID- 24109615
TI  - Study on method to simulate light propagation on tissue with characteristics of
      radial-beam LED based on Monte-Carlo method.
AB  - In biomedical, Monte-carlo simulation is commonly used for simulation of light
      diffusion in tissue. But, most of previous studies did not consider a radial beam
      LED as light source. Therefore, we considered characteristics of a radial beam
      LED and applied them on MC simulation as light source. In this paper, we consider
      3 characteristics of radial beam LED. The first is an initial launch area of
      photons. The second is an incident angle of a photon at an initial photon
      launching area. The third is the refraction effect according to contact area
      between LED and a turbid medium. For the verification of the MC simulation, we
      compared simulation and experimental results. The average of the correlation
      coefficient between simulation and experimental results is 0.9954. Through this
      study, we show an effective method to simulate light diffusion on tissue with
      characteristics for radial beam LED based on MC simulation. 

PMID- 24109616
TI  - A new method to estimate sound energy entering the middle ear.
AB  - Standing waves in the ear canal can cause inaccurate quantification of the sound
      pressure level (SPL) entering the ear and therefore lead to unreliable results in
      clinical tests. Since it is impractical to directly measure the SPL at the
      eardrum position, in this study we proposed a new method to estimate the eardrum
      SPL by solely making measurement at the entry of the ear canal. To achieve this,
      the acoustic characteristics of the earphone were calculated using a calculation
      tube with variable lengths. Then the ear canal impedance was calculated according
      to the obtained source characteristics. Finally, the eardrum SPL was estimated by
      the ear-canal impedance and the SPL measured at the entry of the ear canal. The
      results showed that the eardrum SPL could be reliably estimated for all the five
      subjects participated in this study. The maximal estimation error was less than 3
      dB for all frequencies from 0.5 to 10 kHz. These findings suggested that the
      proposed method could avoid the standing wave problem and therefore might be a
      great candidate for accurate calibration of sound pressure in various acoustic
      measurements. 

PMID- 24109617
TI  - Near-infrared parameters extraction: A potential method to detect skin cancer.
AB  - The wavelength-dependent absorption coefficients can be used to analyse optical
      properties of human skin. Existing absorption models for narrow ranges in the
      visible and near infrared are insufficient to simultaneously incorporate the
      spectral contrast produced by differences in chromophores, water and lipid
      content of skin tissue into skin cancer detection. In the broad range up to 1600
      nm, recent analysis approaches for absorption spectra do not consistently provide
      significant differences between healthy and cancerous skins. We propose an
      absorption model to fit the absorption coefficient spectra of skin samples over
      the range from 400 nm to 1600 nm and an advanced algorithm to find the optimal
      estimation. The extracted parameters of this model are analysed by a statistical
      t-test. The test results demonstrate the significant differences between all
      pairs of tumour-normal skin. Therefore, our approach has strong potential for
      early skin cancer detection using near infrared spectroscopy (NIRS). 

PMID- 24109618
TI  - Electromagnetic tomography via source-space-ICA.
AB  - We propose a technique, called source-space-ICA to provide spatiotemporal
      reconstruction of brain sources. First, the weight-vector-normalized minimum
      variance beamformer is applied to reconstruct the electrical activity of a 3D
      scanning grid which covers the whole brain. Second, principal component analysis
      is used to reduce the dimension of the reconstructed signal matrix of the source
      space, then independent component analysis (ICA) is applied on the resulting
      matrix to identify multiple signal sources in the source-space. Third, the
      demixing weight vectors obtained by ICA for the identified independent components
      are projected back into the SS to obtain tomographic maps of the sources. Besides
      localization, the proposed source-space-ICA approach reconstructs the time-course
      of each source in a single time-series without requiring prior knowledge of
      location, orientation, and number of sources for a given segment of EEG/MEG.
      Simulated EEG was used to evaluate the source-space-ICA. The results show that
      the source-space-ICA approach is able to separate and localize multiple weak
      sources and is robust to interference from other sources as it identifies the
      sources based on their statistical independence. 

PMID- 24109619
TI  - Dipolar source localization from intracerebral SEEG recordings.
AB  - This paper aims at exploring the feasibility of a brain source localization
      method from intracerebral stereo-electroencephalography (SEEG) measurements. The
      SEEG setup consists in multi-contact electrodes inserted in the brain volume,
      each containing about 10 collinear measuring contacts. In clinical context, these
      signals are usually observed using a bipolar montage (potential differences
      between neighbouring contacts of a SEEG electrode). The propagation of distant
      activity is thus suppressed, resulting in the observation of local activities
      around the contacts. We propose in this paper to take benefit of the propagation
      information by considering the original SEEG recordings (common reference
      montage), with the objective to localize sources possibly distant from the
      electrode contacts, and whose activities are propagating through the volume. Our
      method is based on an equivalent dipole model for the source and homogeneous
      infinite models for the propagation environment. This simple approach shows
      satisfactory localization performance under appropriate conditions, described in
      this paper. The proposed method is validated on real SEEG signals for the
      localisation of an intra-cortical electrical stimulation (ICS) generator. 

PMID- 24109620
TI  - Detection of supraventricular and ventricular ectopic beats using a single lead
      ECG.
AB  - Two simple algorithms for supraventricular (SVEB) and ventricular ectopic beat
      (VEB) detection using the electrocardiogram (ECG) are presented. Both algorithms
      use time-domain features and a linear classifier. The first algorithm requires
      QRS detection only and the second algorithm requires P, QRS and T wave
      segmentation. Data was obtained from the 44 non-pacemaker recordings of the MIT
      BIH arrhythmia database and contained approximately 100,000 beats. Performance
      assessment of the best system resulted in an accuracy of 94.4% when
      discriminating SVEB from non-SVEBs and 97.8% in discriminating VEB from non-VEBs.

PMID- 24109621
TI  - Joint symbolic dynamics as an effective approach to study the influence of
      respiratory phase on baroreflex function.
AB  - This study sought to employ a novel approach based on joint symbolic dynamics
      (JSD) to study the influence of respiratory phase on baroreflex function. We
      recorded electrocardiograms (ECG), blood pressure and respiration in 10 (5 male/5
      female) healthy experienced athletes. For our analysis, time series of R-R
      intervals and systolic blood pressure were extracted, and respiratory phases were
      obtained using the Hilbert transform. Based on the changes between successive
      values, each series was transformed into binary symbol vectors, and words of
      length '2' were formed. From parallel analysis of the symbolic dynamics in the
      three time series, the relationship between respiratory phases and baroreflex
      function was quantified. We analysed baroreflex patterns via different word
      combinations for specific respiratory phases and observed that baroreflex
      patterns occurred at similar frequency during expiration, inspiration and phase
      transitions (25.0+/-14.4% vs. 33.4+/-19.5%, expiration-inspiration: 25.0+/-12.6%
      and inspiration-expiration: 22.1+/-17.4%, respectively). From this study, it
      appears that JSD provides a novel and efficient technique for the combined
      analysis of interactions between respiration, heart rate and blood pressure. 

PMID- 24109622
TI  - Automatic drift calibration for EOG-based gaze input interface.
AB  - A drift calibration technique for DC-coupled EOG (electrooculogram) systems is
      proposed. It assumes a non-linear relationship between EOG and eye angle and
      estimates the absolute eye angle by the EOG differences during saccade. Drift is
      calibrated every saccade without user's explicit action, so it is especially
      suitable for long-term gaze input interfaces. An experiment confirms that it can
      estimate horizontal absolute eye angle with an error of about 5 degrees  in
      addition to accurate eye movement. 

PMID- 24109623
TI  - Application of higher order spectra for accurate delineation of atrial
      arrhythmia.
AB  - The electrocardiogram (ECG) is being commonly used as a diagnostic tool to
      distinguish different types of atrial tachyarrhythmias. The inherent complexity
      and mechanistic and clinical inter-relationships often brings about diagnostic
      difficulties to treating physicians and primary health care professionals
      creating frequent misdiagnoses and cross classifications using visual criteria.
      The current paper presents a methodology for ECG based pattern analysis for
      detection of atrial flutter, atrial fibrillation and normal sinus rhythm beats.
      ECG is an inherently non-linear and non-stationary signal; its variation may
      contain indicators of current disease, or warnings about impending cardiac
      diseases. Routinely used time domain and frequency domain methods will not be
      able to capture the hidden information present in the ECG beats. In the present
      study, we have used non-linear features of higher order spectra (HOS) to
      differentiate the normal, atrial fibrillation and atrial flutter ECG beats. The
      bispectrum features were subjected to independent component analysis (ICA) for
      data reduction. The ICA coefficients were subsequently subjected to K-nearest
      neighbor (KNN), classification and regression tree (CART) and neural network (NN)
      classifiers to evaluate the best automated classifier. We have obtained an
      average accuracy of 97.65%, sensitivity and specificity of 98.75% and 99.53%
      respectively using ten-fold cross validation. Overall, the results show that
      application of higher order spectra statistics is useful for the classification
      of atrial tachyarrhythmias with reasonably high accuracies. Further validation of
      the proposed technique will yield acceptable results for clinical implementation.

PMID- 24109625
TI  - Fuzzy central tendency measure for time series variability analysis with
      application to fatigue electromyography signals.
AB  - A new method, namely fuzzy central tendency measure (fCTM) analysis, that could
      enable measurement of the variability of a time series, is presented in this
      study. Tests on simulated data sets show that fCTM is superior to the
      conventional central tendency measure (CTM) in several respects, including
      improved relative consistency and robustness to noise. The proposed fCTM method
      was applied to electromyograph (EMG) signals recorded during sustained isometric
      contraction for tracking local muscle fatigue. The results showed that the fCTM
      increased significantly during the development of muscle fatigue, and it was more
      sensitive to the fatigue phenomenon than mean frequency (MNF), the most commonly
      used muscle fatigue indicator. 

PMID- 24109626
TI  - Multicompartment retinal ganglion cells response to high frequency bi-phasic
      pulse train stimulation: Simulation results.
AB  - Retinal ganglion cells (RGCs) are the sole output neurons of the retina that
      carry information about a visual scene to the brain. By stimulating RGCs with
      electrical stimulation, it is possible to elicit a sensation of light for people
      with macular degeneration or retinitis pigmentosa. To investigate the responses
      of RGCs to high frequency bi-phasic pulse train stimulation, we use previously
      constrained models of multi-compartment OFF RGCs. The morphologies of mouse RGCs
      are taken from the Chalupa set of the NeuroMorpho database. The cell models are
      divided into compartments representing the dendrites, soma and axon that vary
      between the cells. A total of 132 cells are simulated in the NEURON environment.
      Results show that the cell morphology plays an important role in the response
      characteristics of the cell to high frequency bi-phasic pulse train stimulation. 

PMID- 24109628
TI  - Study of the variability of short association bundles on a HARDI database.
AB  - The construction of an atlas of the human brain connectome, in particular, the
      cartography of fiber bundles of superficial white matter (SWM) is a complex and
      unachieved task. Its description is essential for the understanding of human
      brain function and the study of several pathologies. In this work we applied an
      automatic white matter bundle segmentation method proposed in the literature for
      the analysis of the variability of a big amount of superficial white matter
      bundles. The method was applied to 30 subjects of a high quality HARDI database,
      adding several processing steps in order to improve the results. Then we
      calculated some indices for studying the variability of 40 SWM fiber bundles from
      each hemisphere, and we constructed a model of these bundles in the MNI standard
      space. 

PMID- 24109627
TI  - Adapting parcellation schemes to study fetal brain connectivity in serial imaging
      studies.
AB  - A crucial step in studying brain connectivity is the definition of the Regions Of
      Interest (ROI's) which are considered as nodes of a network graph. These ROI's
      identified in structural imaging reflect consistent functional regions in the
      anatomies being compared. However in serial studies of the developing fetal brain
      such functional and associated structural markers are not consistently present
      over time. In this study we adapt two non-atlas based parcellation schemes to
      study the development of connectivity networks of a fetal monkey brain using
      Diffusion Weighted Imaging techniques. Results demonstrate that the fetal brain
      network exhibits small-world characteristics and a pattern of increased cluster
      coefficients and decreased global efficiency. These findings may provide a route
      to creating a new biomarker for healthy fetal brain development. 

PMID- 24109629
TI  - Investigation of muscle degeneration process in young rats with ischemia injury
      using MR diffusion tensor imaging.
AB  - Skeletal muscle is vulnerable to ischemia injury after direct trauma or indirect
      causes. Magnetic resonance diffusion tensor imaging (DTI) has been demonstrated
      to be a powerful tool to investigate muscle structures. However, most previous
      DTI studies that investigated ischemia muscle were performed on mature species,
      results of which may not apply on other age populations, such as young groups. In
      this study, age-related variation of muscle regeneration course after ischemia
      injury was investigated for the first time. Ten young and ten mature SD rats were
      induced ischemia in hindlimbs, and the evolutions of the skeletal muscle
      regeneration were longitudinally studied using DTI before and till 21 days after
      surgery. Results showed that the young group was more sensitive to ischemia and
      recovered more rapidly than the mature one. This study confirms the age-related
      variation of muscle regeneration process, and may provide supplemental
      information for better understanding of muscle repair evolution. 

PMID- 24109630
TI  - Online agglomerative hierarchical clustering of neural fiber tracts.
AB  - We consider the problem of clustering neural fiber pathways, produced from
      diffusion MRI data via tractography, into different bundles. Existing clustering
      methods often suffer from the burden of computing pairwise fiber
      (dis)similarities, which escalates quadratically as the number of fiber pathways
      increases. To address this challenge, we adopt the scenario of clustering data
      streams into the fiber clustering framework. Specifically, we propose to use an
      online hierarchical clustering method, which yields a framework similar to doing
      clustering while simultaneously performing tractography. We evaluate the proposed
      method through experiments on phantom and real diffusion MRI data. Experiments on
      phantom data evaluate the sensitivity of our method to initialization and show
      its superior performance compared with alternative methods. Experiments on real
      data demonstrate the accuracy in clustering selected white matter fiber tracts
      into anatomically consistent bundles. 

PMID- 24109631
TI  - GPU-based acceleration of an automatic white matter segmentation algorithm using
      CUDA.
AB  - This paper presents a parallel implementation of an algorithm for automatic
      segmentation of white matter fibers from tractography data. We execute the
      algorithm in parallel using a high-end video card with a Graphics Processing Unit
      (GPU) as a computation accelerator, using the CUDA language. By exploiting the
      parallelism and the properties of the memory hierarchy available on the GPU, we
      obtain a speedup in execution time of 33.6 with respect to an optimized
      sequential version of the algorithm written in C, and of 240 with respect to the
      original Python/C++ implementation. The execution time is reduced from more than
      two hours to only 35 seconds for a subject dataset of 800,000 fibers, thus
      enabling applications that use interactive segmentation and visualization of
      small to medium-sized tractography datasets. 

PMID- 24109632
TI  - On high order tensor-based diffusivity profile estimation.
AB  - Diffusion weighted magnetic resonance imaging (dMRI) is used to measure, in vivo,
      the self-diffusion of water molecules in biological tissues. High order tensors
      (HOTs) are used to model the apparent diffusion coefficient (ADC) profile at each
      voxel from the dMRI data. In this paper we propose: (i) A new method for
      estimating HOTs from dMRI data based on weighted least squares (WLS)
      optimization; and (ii) A new expression for computing the fractional anisotropy
      from a HOT that does not suffer from singularities and spurious zeros. We also
      present an empirical evaluation of the proposed method relative to the two
      existing methods based on both synthetic and real human brain dMRI data. The
      results show that the proposed method yields more accurate estimation than the
      competing methods. 

PMID- 24109633
TI  - Open system for micro-ultrasound.
AB  - Micro-ultrasound is able to delineate small structures with fine spatial
      resolution on the order of several tens of microns. It is an invaluable imaging
      tool for many clinical and preclinical applications. This paper presents the
      development of an open system for various biomedical studies. The system design
      was based on field programmable gate array (FPGA) embedded in a printed circuit
      board to achieve flexible imaging applications. The major image processing
      algorithms were achieved by the novel field programmable technology for high
      speed and flexibility. Real-time imaging processing was achieved by fast
      processing algorithms and high speed data transfer interface. Extensive tests
      including hardware, algorithms, tissue mimicking phantom, and tissue specimen
      measurements were conducted to demonstrate good performance of the system. Multi
      modality imaging was also facilitated by the developed open system. 

PMID- 24109634
TI  - A high-frequency transimpedance amplifier for CMOS integrated 2D CMUT array
      towards 3D ultrasound imaging.
AB  - One transimpedance amplifier based CMOS analog front-end (AFE) receiver is
      integrated with capacitive micromachined ultrasound transducers (CMUTs) towards
      high frequency 3D ultrasound imaging. Considering device specifications from
      CMUTs, the TIA is designed to amplify received signals from 17.5MHz to 52.5MHz
      with center frequency at 35MHz; and is fabricated in Global Foundry 0.18-um 30-V
      high-voltage (HV) Bipolar/CMOS/DMOS (BCD) process. The measurement results show
      that the TIA with power-supply 6V can reach transimpedance gain of 61dBOmega and
      operating frequency from 17.5MHz to 100MHz. The measured input referred noise is
      27.5pA/?Hz. Acoustic pulse-echo testing is conducted to demonstrate the receiving
      functionality of the designed 3D ultrasound imaging system. 

PMID- 24109635
TI  - Validation of Echo-Dynamography by virtual color doppler echocardiography
      generated from phase contrast magnetic resonance angiography datasets.
AB  - Echo-Dynamography (EDG) is a smart visualization technique in echocardiography in
      which two-dimensional distribution of blood flow vectors in cardiovascular system
      is deduced by applying fluid dynamics theories into Doppler velocity datasets.
      Previous validation studies such as numerical simulation of free jet model or
      model circulation were too simple to reproduce unstable and asymmetrical flow in
      left ventricle. In the present study, virtual color Doppler echocardiography is
      generated from PC-MRA (phase contrast magnetic resonance angiography) datasets.
      EDG is applied on virtual Doppler data and the blood flow vectors are compared
      with those of the original PC-MRA data. EDG-derived blood flow vectors showed
      similar pattern as the original PC-MRA data when blood flow velocity had high
      value. The errors were caused from underestimating the magnitude of vortex flow
      component in the flow field near the boundary of the left ventricular wall. The
      results also indicated that apical long axis view had small error compared with
      parasternal long axis view. Despite EDG method causes small errors, it provides
      important information on blood flow dynamics in most parts. 

PMID- 24109636
TI  - Mixture noise removal in ultrasound images using SCoBeP and low-rank matrix
      completion.
AB  - Denoising as one of the most significant tools in ultrasound imaging was studied
      widely in the literature. However, most existing ultrasound image denoising
      algorithms have assumed the additive white Gaussian noise. In this work, we
      propose two efficient ultrasound image denoising methods that can handle a noise
      mixture of various types. Our methods are based on SCoBeP and low-rank matrix
      completion as follows. In our first method, a noisy image is processed in
      blockwise manner and for each processed block we find candidate match pixels on
      other images using sparse coding and belief propagation, where in our second
      algorithm, we use overlapped patches to further lower the computation complexity.
      The blocks centered around these candidate pixels then will stack together and
      unreliable pixels will be removed using fast matrix completion method. We
      demonstrate the effectiveness of our algorithm in removing the mixed noise
      through the results. We also compare with other denoising technique using matrix
      completion. Our methods results in comparable performance with significantly
      lower computation complexity.

PMID- 24109637
TI  - In vivo patient measurements of bladder elasticity using Ultrasound Bladder
      Vibrometry (UBV).
AB  - A healthy compliant bladder is capable of storing increasing volumes of urine at
      low pressures. The loss of bladder compliance is associated with various
      diseases. The urodynamic studies (UDS), the current clinical gold standard for
      measuring bladder compliance, requires catheterization and measuring intra
      bladder pressure as a function of filling volumes. Ultrasound Bladder Vibrometry
      (UBV) is a noninvasive technique that uses focused ultrasound radiation force to
      excite Lamb waves in the bladder wall and pulse-echo techniques to track the wave
      motion in tissue. Cross-spectral analysis is used to calculate the wave velocity,
      which is directly related to the elastic properties of the bladder wall. In this
      study, we compare the measurements of changes in bladder elasticity as a function
      of bladder pressure and volume obtained using UBV and the pressure-volume
      measurements obtained using UDS. UBV and UDS of an excised porcine bladder are
      presented. Comparative studies in neurogenic and healthy patient bladders are
      also summarized. 

PMID- 24109638
TI  - Dynamic method of optical coherence elastography in determining viscoelasticity
      of polymers and tissues.
AB  - In this paper, we report on a novel quantitative elastography technique that
      combines optical coherence tomography (OCT) with acoustic radiation force (ARF)
      excitation to estimate the complex modulus. Sinusoidally modulated ARF
      excitations between 200 - 4000 Hz generate a surface wave at the tissue surface
      that can be related to bulk viscoelastic (VE) properties in a manner that is both
      precise and quantitative. This method is very well suited to studying media at
      high spatial resolution and over a very broad range of force frequencies.
      Mechanical characterization was calibrated using hydropolymers before studying
      liver samples. Fresh porcine liver samples were measured over time with and
      without formalin fixation. These data were used to evaluate the utility of the
      Kelvin-Voigt rheological model commonly used to fit dispersion data when
      estimating modulus values. We also investigated use of square-wave force
      excitation to measure the step response of tissues. 

PMID- 24109639
TI  - New methods for quantifying and visualizing information from images of cells: An
      overview.
AB  - New microscopy imaging techniques have enabled the acquisition of cellular and
      sub-cellular information with unprecedented accuracy and specificity.
      Fluorescence techniques have enabled labeling of numerous, previously
      inaccessible, molecules and organelles, while Raman spectrographic techniques,
      for example, have enabled label free acquisition. Together with the development
      of high throughput techniques, these technologies now allow for the acquisition
      of a significant amount of information about cellular processes and have enabled
      high throughput and high content screening. Beyond image formation and
      acquisition, computational techniques comprise an important part of the process
      of obtaining biological understanding from such experiments. Here we review the
      pros and cons of the main approaches that have been used to extract information
      from digital images of cells. In addition, we also offer an overview of modern
      computational techniques that beyond allowing for discrimination between two
      hypothesis, also allow for modeling, visualization, and understanding of
      biological phenomena. 

PMID- 24109640
TI  - Live imaging of transgenic mice expressing FRET biosensors.
AB  - In recent years, fluorescence imaging has received particular attention, due to
      increasing availabilities of fluorescent proteins and dyes, which had driven the
      development of novel biosensors. Genetically-encoded biosensors based on the
      principle of Forster resonance energy transfer (FRET) have been widely used in
      biology to visualize the spatiotemporal dynamics of signaling molecules. Despite
      the increasing multitude of these biosensors, their application has been mostly
      limited to cultured cells with transient biosensor expression, due to
      difficulties in stable expression of FRET biosensors. In this study, we report
      efficient generation of transgenic mouse lines expressing heritable and
      functional biosensors for ERK and PKA. These transgenic mice were generated by
      the cytoplasmic co-injection of Tol2 transposase mRNA and a circular plasmid
      harboring Tol2 recombination sites. Observation of these transgenic mice by two
      photon excitation microscopy yielded real-time activity maps of ERK and PKA in
      various tissues, with greatly improved signal-to-background ratios. Our
      transgenic mice may be bred into diverse genetic backgrounds; moreover, the
      protocol we have developed paves the way for the generation of transgenic mice
      that express other FRET biosensors, with important applications in the
      characterization of physiological and pathological signal transduction events in
      addition to drug development and screening. 

PMID- 24109641
TI  - Ultrafast automated image cytometry for cancer detection.
AB  - We present a method for ultrafast automated single-cell optical microscopy that
      performs blur-free image acquisition and non-stop real-time image-recording and
      classification of cells during high-speed flow. This method is based on a unique
      integration of ultrafast optical imaging, self-focusing microfluidics,
      optoelectronics, and information technology. To show the system's utility, we
      demonstrate high-throughput image-based screening of rare breast cancer cells in
      blood with an unprecedented throughput of 100,000 cells/s and a record false
      positive rate of one in a million. This method is expected to be effective for
      early, noninvasive, low-cost detection of cancer. 

PMID- 24109642
TI  - Super-resolution confocal live imaging microscopy (SCLIM) - Cutting-edge
      technology in cell biology.
AB  - Super-resolution confocal live imaging microscopy (SCLIM) we developed provides
      amazingly high-speed live cell imaging at high space resolution. With this
      technology we are now able to observe details of membrane traffic events,
      including behaviors of small vesicles, cisternal maturation of the Golgi
      apparatus, and membrane segregation within a compartment. 

PMID- 24109643
TI  - A quantitative analysis of F-actin features and distribution in fluorescence
      microscopy images to distinguish cells with different modes of motility.
AB  - Actin is one of the most abundant proteins in eukaryote cells, playing a key role
      in cell dynamic morphological alterations and tumor metastatic spread. To
      investigate the relationship between the distribution patterns of actin and the
      aggressiveness of cancer cells, we developed an image analysis framework for
      quantifying cell F-actin distributions examined with fluorescence microscopy. The
      images are first segmented with multichannel information of both F-actin and
      nuclear staining. Using the watershed method and Voronoi tessellation, the cells
      can be well segmented based on both F-actin and nuclear information. Altogether,
      sixteen F-actin distribution features are calculated for each individual cell. A
      linear Support Vector Machine (SVM) is then applied in the feature space to
      separate cells with different modes of motility. Our results show that cells with
      different modes of motility can be distinguished by F-actin distributions. To our
      knowledge, this is the first study managing to distinguish cancer cells with
      different aggressiveness based on quantitative analysis of F-actin distribution
      patterns. 

PMID- 24109644
TI  - An ergonomic, instrumented ultrasound probe for 6-axis force/torque measurement.
AB  - An ergonomic, instrumented ultrasound probe has been developed for medical
      imaging applications. The device, which fits compactly in the hand of
      sonographers and permits rapid attachment & removal of the ultrasound probe,
      measures ultrasound probe-to-patient contact forces and torques in all six axes.
      The device was used to measure contact forces and torques applied by ten
      professional sonographers on five patients during thirty-six abdominal exams. Of
      the three contact forces, those applied along the probe axis were found to be
      largest, averaging 7.0N. Measurement noise was quantified for each axis, and
      found to be small compared with the axial force. Understanding the range of
      forces applied during ultrasound imaging enables the design of more accurate
      robotic imaging systems and could also improve understanding of the correlation
      between contact force and sonographer fatigue and injury. 

PMID- 24109645
TI  - Development of an arthroscopic ultrasound probe for assessment of articular
      cartilage degeneration.
AB  - Quantitative assessment of articular cartilage is important for the early
      diagnosis of osteoarthritis, intra-operation joint tissue evaluation and judgment
      of repaired cartilage quality. This technique is also applicable to the cartilage
      if arthroscopic instrument embedding this technique can be developed. In this
      study, an arthroscopic water-jet ultrasound indentation probe was developed with
      the help of a small profile intra-articular ultrasound imaging (IAUS) catheter
      for the intra-articular measurement of cartilage condition. The probe can provide
      measurement of morphological, acoustical and mechanical properties of articular
      cartilage. Preliminary tests were conducted on 10 intact porcine knees with the
      guide of arthroscopy for the evaluation of cartilage degeneration, which was
      induced by trypsin digestion. Results showed the cartilage stiffness decreased
      significantly after the digestion (p < 0.001) with the measurement conducted by
      the developed probe. In summary, an arthroscopic ultrasound probe has been
      successfully developed and its utility in detecting the cartilage degeneration
      was demonstrated in this study. Future work includes the improvement of the probe
      design and studies on measurement of animal or human samples in vivo. 

PMID- 24109646
TI  - Integrated MEMS platform with silicon nanotweezers and open microfluidic device
      for real-time and routine biomechanical probing on molecules and cells.
AB  - This paper describes an integrated biomechanical platform for real-time molecular
      or cellular assays. This platform is composed of silicon nanotweezers to
      manipulate the biological samples and an open microfluidic to handle solution and
      reactive agents. The tweezers are fabricated by standard Silicon-On-Insulator
      based micromachining processes (2 masks +1 additional mask for special tips) and
      integrate actuator, trapping tips and sensor. The microfluidic device is produced
      from common polydimethylsiloxane (PDMS) micromolding and integrates active valves
      for controlling the biological medium. Combining both technologies, a versatile
      experimental setup, built up in an enclosed space (< 10 cm(3)), enables direct
      interrogation of molecules or cells in solution. The silicon nanotweezers sense
      slight biological modifications of the trapped molecules or cell by monitoring
      the mechanical resonance response, which keeps a high Q factor (over 20) in
      liquid. Biomolecular assays (molecule trapping and enzymatic reaction kinetics)
      as well as characterizations of cells are reported here. The system provide
      molecular level resolution and is sensitive enough to capture cell biomechano
      transduction activities. Moreover as the system is handy, it may be an easy, fast
      and quantitative alternative to existing methods. 

PMID- 24109647
TI  - Load Monitoring System for Partial Weight Bearing Therapy for rehabilitation of
      lower extremity fractures.
AB  - Partial Weight Bearing Therapy (PWB) is used during in rehabilitation of lower
      extremity fractures, but optimal outcomes are limited by the paucity of data
      supporting the current standard of care, the inability of clinicians to assess
      patients' compliance to the prescribed therapy, and by the patient's inability to
      apply clinical loading guidelines. To address these needs a Load Monitoring
      System (LMS) was developed using a novel long-term load measuring technology
      coupled with consumer electronics for storing and reporting of patient limb
      loading data. The project was planned as a staged effort and the results of the
      first stage development are presented here. During the first stage of this
      project, the LMS insole load sensor was developed for 6-week standalone
      operation. The LMS was subjected to bench-testing, demonstrating low static and
      dynamic drift. 

PMID- 24109648
TI  - A novel method for monolithic fabrication of polymer microneedles on a platform
      for transdermal drug delivery.
AB  - This paper reports on the creation of a novel method for monolithic fabrication
      of out-of-plane polymer (SU-8) microneedles incorporating sharpness of needle
      tips, hollowness of needle lumen as well as a platform on which the microneedles
      stand orthogonally with the hollow of the needle lumen continuous through the
      platform. In essence, both the microneedle as well as the platform on which it
      stands, are made of the same polymer material, rendering the process monolithic.
      The microneedle tips produced were quite sharp with tip diameters ranging between
      5 to 10 um, needle heights greater than 1 mm and resulting aspect ratio of 40.
      Further, mechanical tests performed on the fabricated microneedles demonstrate a
      critical compressive failure load of about 173 mN on average per microneedle,
      which translates into a safety factor greater than one for skin penetration. 

PMID- 24109649
TI  - Transplantation tool integrated with MEMS manipulator for retinal pigment
      epithelium cell sheet.
AB  - This paper reports a transplantation tool for the retinal pigment epithelium in
      an eye. We have developed MEMS manipulator as an end-effector for transplantation
      of retinal pigment epithelium cell sheet. Typical size of MEMS manipulator is
      3mm*3mm. MEMS manipulator was made of polydimethylsiloxane and driven by
      pneumatic balloon actuators. MEMS manipulator have been improved and integrated
      with several functions by sensors and actuators. MEMS manipulator is integrated
      into a transplantation tool. A whole tool also requires improvements based on our
      experimental results. We have improved our tool in terms of assembling, sealing,
      and operation. 

PMID- 24109650
TI  - A CMOS enhanced solid-state nanopore based single molecule detection platform.
AB  - Solid-state nanopores have emerged as a single molecule label-free electronic
      detection platform. Existing transimpedance stages used to measure ionic current
      nanopores suffer from dynamic range limitations resulting from steady-state
      baseline currents. We propose a digitally-assisted baseline cancellation CMOS
      platform that circumvents this issue. Since baseline cancellation is a form of
      auto-zeroing, the 1/f noise of the system is also reduced. Our proposed design
      can tolerate a steady state baseline current of 10uA and has a usable bandwidth
      of 750kHz. Quantitative DNA translocation experiments on 5kbp DNA was performed
      using a 5nm silicon nitride pore using both the CMOS platform and a commercial
      system. Comparison of event-count histograms show that the CMOS platform clearly
      outperforms the commercial system, allowing for unambiguous interpretation of the
      data. 

PMID- 24109651
TI  - Development of a paper-based carbon nanotube sensing microfluidic device for
      biological detection.
AB  - Carbon nanotube (CNT) has been utilized for the biological detection due to its
      extremely sensitive to biological molecules. A paper-based CNT sensing
      microfluidic device has been developed for the detection of protein, i.e., biotin
      avidin, binding. We have developed a fabrication method that allows controlled
      deposition of bundled CNTs with well-defined dimensions to form sensors on paper.
      Then, polydimethyl siloxane (PDMS) was used to pattern the hydrophobic boundary
      on paper to form the reaction sites. The proposed fabrication method is based on
      vacuum filtration process with a metal mask covering on a filter paper for the
      definition of the dimension of sensor. The length, width, and thickness of the
      CNT-based sensors are readily controlled by the metal mask and the weight of the
      CNT powder used during the filtration process, respectively. Homogeneous
      deposition of CNTs with well-defined dimensions can be achieved. The CNT-based
      sensor on paper has been demonstrated on the detection of the protein binding.
      Biotin was first immobilized on the CNT's sidewall and avidin suspended solution
      was applied to the site. The result of the biotin-avidin binding was measured by
      the resistance change of the sensor, which is a label-free detection method. It
      showed the CNT is sensitive to the biological molecules and the proposed paper
      based CNT sensing device is a possible candidate for point-of-care biosensors.
      Thus, electrical bio-assays on paper-based microfluidics can be realized to
      develop low cost, sensitive, and specific diagnostic devices. 

PMID- 24109652
TI  - A novel bioelectronic glucose sensor to process distinct electrical activities of
      pancreatic beta-cells.
AB  - Glucose sensors have improved and facilitated therapy for type 1 diabetes.
      However, they are still not capable to sense all physiological signals and to act
      in a closed-loop. Pancreatic beta-cells have been shaped during evolution as
      biological sensors and offer the advantage to integrate all physiological signals
      in addition to glucose. Moreover, biosensors based on these cells may also serve
      for non-invasive and continuous long-term characterization of beta-cells, drug
      research, tissue engineering and pre-transplantation quality control. beta-cells
      alter their electrical activity upon exposure to glucose and physiological
      hormones and we have used these properties to design a biosensor. To this end
      signals were recorded extracellularly from islet cells kept on multi-electrode
      arrays. Slow and rapid oscillations were observed, both modulated by glucose.
      Especially slow oscillations are very robust and have an excellent signal/noise
      ratio. Signal processing functions were designed to separate the two activities
      to extract and analyze relevant parameters. These parameters correlate very well
      with either increasing or decreasing glucose concentrations. An electronic device
      is under construction, based on an embedded FPGA capable of processing multiple
      channels in parallel. In the future, such a device shall be used as a portable
      real-time biosensor regulating insulin delivery from a pump. 

PMID- 24109653
TI  - Novel device to trend impedance and fluorescence of the cervix for preterm birth
      detection.
AB  - Preterm birth is the leading cause of worldwide neonatal mortality. It follows a
      pathologically accelerated form of the normal processes that govern cervical
      softening and dilation. Softening and dilation occur due to changes in cervical
      collagen crosslinking, which can be measured non-invasively by changes in tissue
      fluorescence and impedance. We present a novel device designed specifically to
      take fluorescence and impedance measurements throughout pregnancy, with the end
      goal of fusing and trending these measurements to form an early diagnosis of
      preterm labor. 

PMID- 24109654
TI  - Non-invasive measurement of cell viability in 3-dimensional cell culture
      construct.
AB  - In this work, a non-invasive measurement technique for the quantitative
      determination of cell viability in a three-dimensional (3D) cell culture
      construct is proposed. This technique is based on on-site electrical impedance
      measurement. A microfluidic chip with a 3D culture chamber is fabricated to
      demonstrate this technique. In vitro 3D cell culture has been interpreted for
      faithfully representation of the in vivo cellular responses in 3D cell culture
      construct is normally time-consuming and labor-intensive. In this study, the
      microfluidic chip consists of a culture chamber, in which a pair of vertical
      electrodes at its opposite sidewalls was embedded, and a fluidic channel for drug
      perfusion. Cancer cells encapsulated in agarose gel were loaded into the culture
      chamber to perform 3D cell culture under the perfusion of culture medium and anti
      cancer drug in different concentrations (6, 12, 18, and 24 ug/ml) for 2 days.
      Since higher drug concentration led to more cell damage or death, the total
      impedance magnitude of the culture construct was shown to be reasonably
      proportional to the anti-cancer drug concentration. Moreover, cell proliferation
      can be also monitored using this technique. The proposed measurement method can
      determine cell viability without affecting the cellular behaviors during culture.
      It has a high potential to develop a fast and easy measurement compared with the
      conventional cellular analysis techniques. 

PMID- 24109655
TI  - Novel platinum black electroplating technique improving mechanical stability.
AB  - Platinum black microelectrodes are widely used as an effective neural signal
      recording sensor. The simple fabrication process, high quality signal recording
      and proper biocompatibility are the main advantages of platinum black
      microelectrodes. When microelectrodes are exposed to actual biological system,
      various physical stimuli are applied. However, the porous structure of platinum
      black is vulnerable to external stimuli and destroyed easily. The impedance level
      of the microelectrode increases when the microelectrodes are damaged resulting in
      decreased recording performance. In this study, we developed mechanically stable
      platinum black microelectrodes by adding polydopamine. The polydopamine layer was
      added between the platinum black structures by electrodeposition method. The
      initial impedance level of platinum black only microelectrodes and polydopamine
      added microelectrodes were similar but after applying ultrasonication the
      impedance value dramatically increased for platinum black only microelectrodes,
      whereas polydopamine added microelectrodes showed little increase which were
      nearly retained initial values. Polydopamine added platinum black microelectrodes
      are expected to extend the availability as neural sensors. 

PMID- 24109656
TI  - Osteoporosis risk prediction using machine learning and conventional methods.
AB  - A number of clinical decision tools for osteoporosis risk assessment have been
      developed to select postmenopausal women for the measurement of bone mineral
      density. We developed and validated machine learning models with the aim of more
      accurately identifying the risk of osteoporosis in postmenopausal women, and
      compared with the ability of a conventional clinical decision tool, osteoporosis
      self-assessment tool (OST). We collected medical records from Korean
      postmenopausal women based on the Korea National Health and Nutrition Surveys
      (KNHANES V-1). The training data set was used to construct models based on
      popular machine learning algorithms such as support vector machines (SVM), random
      forests (RF), artificial neural networks (ANN), and logistic regression (LR)
      based on various predictors associated with low bone density. The learning models
      were compared with OST. SVM had significantly better area under the curve (AUC)
      of the receiver operating characteristic (ROC) than ANN, LR, and OST. Validation
      on the test set showed that SVM predicted osteoporosis risk with an AUC of 0.827,
      accuracy of 76.7%, sensitivity of 77.8%, and specificity of 76.0%. We were the
      first to perform comparisons of the performance of osteoporosis prediction
      between the machine learning and conventional methods using population-based
      epidemiological data. The machine learning methods may be effective tools for
      identifying postmenopausal women at high risk for osteoporosis. 

PMID- 24109657
TI  - Interpretation of movement during stair ascent for predicting severity and
      prognosis of knee osteoarthritis in elderly women using support vector machine.
AB  - Several studies have demonstrated that pathologic movement changes in knee
      osteoarthritis (OA) may contribute to disease progression. The aim of this study
      was to investigate the association between movement changes during stair ascent
      and pain, radiographic severity, and prognosis of knee OA in the elderly women
      using machine learning (ML) over a seven-year follow-up period. Eighteen elderly
      female patients with knee OA and 20 healthy controls were enrolled. Kinematic
      data for stair ascent were obtained using a 3D-motion analysis system at
      baseline. Kinematic factors were analyzed based on one of the popular ML methods,
      support vector machines (SVM). SVM was used to search kinematic predictors
      associated with pain, radiographic severity of knee OA, and unfavorable outcomes,
      which were defined as persistent knee pain as reported at the seven-year follow
      up or as having undergone total knee replacement during the follow-up period. Six
      patients (46.2%) had unfavorable outcomes at the seven-year follow-up. SVM showed
      accuracy of detection of knee OA (97.4%), prediction of pain (83.3%),
      radiographic severity (83.3%), and unfavorable outcomes (69.2%). The predictors
      with SVM included the time of stair ascent, maximal anterior pelvis tilting, knee
      flexion at initial foot contact, and ankle dorsiflexion at initial foot contact.
      The interpretation of movement during stair ascent using ML may be helpful for
      physicians not only in detecting knee OA, but also in evaluating pain and
      radiographic severity. 

PMID- 24109658
TI  - Taking a break from chemotherapy to fight drug-resistance: The cases of cancer
      and HIV/AIDS.
AB  - In this work, we present how optimized treatment interruptions during
      chemotherapy may be used to control drug-resistance, a major challenge for
      clinicians worldwide. Specifically, we examine resistance in cancer and HIV/AIDS.
      For each disease, we use mathematical models alongside real data to represent the
      respective complex biological phenomena and optimal control algorithms to design
      optimized treatment schedules aiming at controlling disease progression and
      patient death. In both diseases, it is shown that the key to controlling
      resistance is the optimal management of the frequency and magnitude of treatment
      interruptions as a way to facilitate the interplay between the competitive
      resistant/sensitive strains. 

PMID- 24109659
TI  - High-order sliding-mode control for anesthesia.
AB  - Depth of anesthesia can be indirectly measured by Bispectral Index (BIS),
      therefore it is possible to administer propofol in a closed loop to maintain the
      optimal level of anesthesia while minimizing the dose to improve the
      postanesthesia recovery. High-Order Sliding-Mode control can be used to
      individualize drug dosing. In this study, the controller is tested with four in
      silico patients. 

PMID- 24109660
TI  - A model-based control protocol for transition from ICU to HDU: Robustness
      analysis.
AB  - The robustness of a model-based control protocol as a less intensive TGC protocol
      using insulin Glargine for provision of basal insulin is simulated in this study.
      To quantify the performance and robustness of the protocol to errors, namely
      physiological variability and sensor errors, an in-silico Monte Carlo analysis is
      performed. Actual patient data from Christchurch Hospital, New Zealand were used
      as virtual trial patients. 

PMID- 24109662
TI  - Assessment of conceptual inconsistencies in the hybrid reservoir-wave model.
AB  - The reservoir-wave paradigm separates pressure into windkessel-related
      'reservoir' and wave-related 'excess' components, however the conceptual validity
      of this approach has not been sufficiently scrutinized. This paper assesses two
      logical implications of the reservoir-wave concept. First, parameters defining
      the reservoir (resistance and compliance) should be independent of wave effects.
      Second, wave analysis performed using excess pressure should provide a more
      accurate and physically intuitive representation of wave propagation and
      reflection in a vascular system, compared with the traditional wave analysis
      based on unseparated pressure. These issues were investigated with one
      dimensional numerical models. Using a single vessel model, reservoir parameters
      were shown to be highly influenced by wave propagation effects. In a single
      bifurcation model, wave analysis based on excess pressure underestimated the
      reflection coefficient of the known impedance mismatch at the junction,
      overestimated the distance to this reflection site, and exhibited backward
      expansion waves suggestive of multiple negative impedance mismatches that did not
      exist in the system. Traditional wave analysis accurately and intuitively
      described waves. The identified conceptual inconsistencies in the reservoir-wave
      paradigm may arise from the use of hybrid (0D and 1D) dimensionality, rather than
      a hierarchical approach to model dimensionality. 

PMID- 24109661
TI  - Shape model of the maxillary dental arch using Fourier descriptors with an
      application in the rehabilitation for edentulous patient.
AB  - The knowledge of teeth positions on the maxillary arch is useful in the
      rehabilitation of the edentulous patient. A combination of angular (theta), and
      linear (l) variables representing position of four teeth were initially proposed
      as the shape descriptor of the maxillary dental arch. Three categories of shape
      were established, each having a multivariate normal distribution. It may be
      argued that 4 selected teeth on the standardized digital images of the dental
      casts could be considered as insufficient with respect to representing shape.
      However, increasing the number of points would create problems with dimensions
      and proof of existence of the multivariate normal distribution is extremely
      difficult. This study investigates the ability of Fourier descriptors (FD) using
      all maxillary teeth to find alternative shape models. Eight FD terms were
      sufficient to represent 21 points on the arch. Using these 8 FD terms as an
      alternative shape descriptor, three categories of shape were verified, each
      category having the complex normal distribution. 

PMID- 24109663
TI  - Application of cardiovascular models in comparative physiology and blood pressure
      variability.
AB  - The usefulness of cardiovascular models is determined by their intended function
      with respect to elucidating underlying hemodynamic concepts and to enable
      simulations that will assist in understanding the effects of specific parameters.
      Models can take different forms, including mock circulatory constructs with
      physical components, mathematical representations of parameter space relations
      employing constitutive equations, or closed form representations of electrical
      circuit analogs described in the time or frequency domain. This investigation
      describes the use of cardiovascular models based on electrical analogs of
      mechanical hydrodynamic systems to elucidate two different physiologic concepts:
      (i) the use of distributed vascular impedance to investigate comparative
      physiology of optimal design and features related to body size across a broad
      range of animal species; (ii) use of lumped parameter models to assess the role
      of arterial stiffness in blood pressure variability. The impedance model shows
      that an allometric relationship between body weight and aortic effective length
      can be determined by using the frequency of minimum input impedance and aortic
      pulse wave velocity. This concept provides a background for optimal matching of
      body size and hemodynamic load on the heart. The lumped parameter model indicates
      that arterial stiffness, simulated by the total arterial compliance term, has a
      significant impact on variability of arterial pressure when changes are due to
      dynamic alterations of peripheral resistance. In addition, the known pressure
      dependency of arterial stiffness results in a curvilinear relationship between
      blood pressure variability and mean pressure. This has implications in
      hypertensive treatment where there are marked changes in arterial stiffness, as
      occurs with aging. 

PMID- 24109664
TI  - Basis of monitoring central blood pressure and hemodynamic parameters by
      peripheral arterial pulse waveform analyses.
AB  - In hypertension clinics, central blood pressure (CBP) should be estimated,
      instead of directly measured, by the "signal processing" of a noninvasive
      peripheral pressure waveform. This paper deals with the data obtained in our
      three separate studies focusing on a major estimation method, i.e., radial artery
      late systolic shoulder pressure (rSBP2)-based CBP estimation. Study 1: Using a
      wave separation analysis of precise animal data of pressure wave transmission
      along the upper-limb arteries, we first demonstrate that pulse pressure
      amplification is largely attributable to local wave reflection alone. Study 2: A
      frequency component analysis of simultaneously recorded human central and radial
      artery pressure waveforms showed a predominance of lower (1st+2nd) harmonic
      components in determining the central augmentation peak amplitude. The features
      of a central pressure waveform, including its phase property, may contribute to
      the less-altered transmission of augmentation peak pressure to rSBP2. Study 3:
      Comparisons of noninvasive rSBP2 with direct or estimated central systolic blood
      pressure (cSBP) revealed broad agreement but also augmentation-dependent biases.
      Based on the features of the biases as well as the counterbalanced relationship
      between pulse pressure amplification and the transmission-induced alterations of
      augmentation peak amplitude observed in Study 2, we propose an improved cSBP
      estimate, SBPm, the simple arithmetic mean of rSBP2 and peripheral systolic blood
      pressure.

PMID- 24109665
TI  - A comparative analysis of reduced arterial models for hemodynamic monitoring.
AB  - We performed a comparative analysis of reduced arterial models. These models are
      characterized by a few parameters that can be uniquely estimated from the limited
      measurements often available in practice. Hence, they offer a means to improve
      hemodynamic monitoring. We specifically describe Windkessel, transmission-line,
      and recursive difference equation models, show how they are related, pinpoint
      their capabilities and limitations, and review how we have applied them for less
      invasive cardiac output monitoring. 

PMID- 24109666
TI  - The importance of wave reflection: A comparison of wave intensity analysis and
      separation of pressure into forward and backward components.
AB  - Waves and wave reflections play an undoubted role in arterial hemodynamics. Wave
      intensity analysis and separation of pressure into forward and backward
      components can both be used to analyze wave phenomena in arteries, but result in
      different interpretations regarding the contribution of wave reflections to the
      aorta blood pressure waveform. We compare these approaches using pressure and
      flow measurements made in the human aorta and discuss why the interpretations
      might differ. 

PMID- 24109667
TI  - The barriers to clinical application of non-invasively obtained central blood
      pressure.
AB  - With the demonstration of superior prognostic value of central blood pressure
      (CBP) beyond traditionally used brachial BP, there have been increasing interest
      in the development of novel devices reporting parameters of CBP. The emerging
      devices for non-invasive estimation of CBP, based on either tonometry-based or
      cuff-based techniques, were evaluated with various validation studies. Therefore,
      the research community and clinicians have been faced with challenges regarding
      the conduction and interpretation of the validation studies for the non
      invasively obtained CBP. We summarize here the barriers to the clinical
      application of the CBP concept, which provide research opportunities to further
      the subsequent translation. 

PMID- 24109668
TI  - Computational model of cerebellar transcranial direct current stimulation.
AB  - This work aimed to estimate the distribution of the electric field and current
      density generated by cerebellar tDCS using electromagnetics computational
      techniques applied to a realistic human models of different ages and gender.
      Results show that the stronger electric field and current density occur mainly in
      the cerebellar cortex, with a spread toward the occipital region of the cortex,
      while the current spread to other structures is negligible. Moreover, changes of
      about 1 cm in the position of the scalp electrode delivering tDCS did not
      influence the E and J distribution in the cerebellum. 

PMID- 24109669
TI  - Comparison of neuronal excitation between extruded slab partial head model and
      full head model in subdural cortical stimulation.
AB  - Cortical stimulation (CS) is an appealing and emerging treatment for neurological
      disorders. CS is known to promote functional recovery effectively; however, its
      underlying mechanism and the optimal parameters for the effective treatment are
      not clearly understood. In this work, we developed a realistic three-dimensional
      full head and chest model for subdural CS. Our proposed model was compared at the
      neuron level with an existing simplified extruded slab partial head model
      depicting around precentral gyral cortex only. Each model was coupled with the
      pyramidal neuronal model in order to investigate an extent of neuronal
      excitation. We found that the crown of the cortex was the most excitable area in
      the unipolar stimulation, while in the bipolar stimulation, the lip and bank were
      excited more easily than other areas. Finally, it was evident that our proposed
      model was substantially different in excitation threshold from the existing
      simplified model, which is compelling to do computational CS study on more
      realistic head models. 

PMID- 24109670
TI  - Equalization for intracortical microstimulation artifact reduction.
AB  - We present a method for decreasing the duration of artifacts present during intra
      cortical microstimulation (ICMS) recordings by using techniques developed for
      digital communications. We replace the traditional monophasic or biphasic current
      stimulation pulse with a patterned pulse stream produced by a Zero Forcing
      Equalizer (ZFE) filter after characterizing the artifact as a communications
      channel. The results find that using the ZFE stimulus has the potential to reduce
      artifact width by more than 70%. Considerations for the hardware implementation
      of the equalizer are presented. 

PMID- 24109671
TI  - Integrated slanted microneedle-LED array for optogenetics.
AB  - This paper presents a three-dimensional (3-D) flexible micro light emitting diode
      (MU-LED) array for selective optical stimulation of cortical neurons. The array
      integrated individually addressable MU-LED chips with slanted polymer-based
      microneedle waveguides to allow precise light delivery to multiple cortical
      layers simultaneously. A droplet backside exposure method was developed to
      monolithically fabricate slanted microneedles on a single polymer platform. A
      wafer-level assembly technique was demonstrated, which permits large-scale, high
      density system integration. The electrical, optical, thermal, and mechanical
      properties of the 3-D slanted microneedle-LED array were characterized
      experimentally. 

PMID- 24109672
TI  - Multiple optical stimulation to neuron using Si opto-neural probe with multiple
      optical waveguides and metal-cover for optogenetics.
AB  - We have developed a Si opt-neural probe with multiple waveguides and metal cover
      for highly accurate optical stimulation. This neural probe had 16 recording
      sites, three optical waveguides, and metal cover for suppressing light leakage.
      We evaluated electrochemical properties of the recording sites, and confirmed
      that the neural probe had suitable characteristics for neural recording. We also
      demonstrated the optical stimulation to the neurons expressing ChR2 using our
      probe. As a result, we succeeded multisite optical stimulation, and observed that
      no light leakage from the optical waveguides because of the metal cover. From in
      vivo experiments, we successfully recorded optically modulated local field
      potential using the fabricated Si neural probe with optical waveguides. Moreover,
      we applied current source density analysis to the recorded LFPs. As a result, we
      confirmed that light induced membrane current sink in locally stimulated area.
      Our Si opto-neural probe with multiple optical waveguides and metal-cover is one
      of the most versatile tools for optogenetics. 

PMID- 24109673
TI  - Performance of a high-speed transcutaneous link with error correction coding.
AB  - Several low-power communication strategies have been studied for interfacing with
      cortical implants via mutual inductance links. In this paper, we consider
      performance optimization strategies for a mutual-inductance link based on the
      Pulse Harmonic Modulation method. We consider two enhancements that may allow for
      increased throughput in the PHM system. First, a low-power error-correcting code
      is used to improve the system's robustness against noise, timing jitter and other
      non-ideal factors. Second, the system is adapted for multi-level modulation as a
      means of increasing the data rate. Our results characterize each systems' bit
      error rate as a function of pulse jitter, power interference and comparator
      offset. 

PMID- 24109674
TI  - Motor imagery BCI for upper limb stroke rehabilitation: An evaluation of the EEG
      recordings using coherence analysis.
AB  - Brain-computer interface (BCI) technology has the potential as a post-stroke
      rehabilitation tool, and the efficacy of the technology is most often
      demonstrated through output peripherals such as robots, orthosis and computers.
      In this study, the EEG signals recorded during the course of upper limb stroke
      rehabilitaion using motor imagery BCI were analyzed to better understand the
      effect of BCI therapy for post-stroke rehabilitation. The stroke patients
      recruited underwent 10 sessions of 1-hour BCI with robotic feedback for 2 weeks,
      5 times a week. The analysis was performed by computing the coherences of the EEG
      in the lesion and contralesion side of the hemisphere from each session, and the
      coherence index of the lesion hemisphere (0 <= CI <= 1) was computed. The
      coherence index represents the rate of activation of the lesion hemisphere, and
      the correlation with the Fugl-Meyer assessment (FMA) before and after the BCI
      therapy was investigated. Significant improvement in the FMA scores was reported
      for five of the six patients (p = 0.01). The analysis showed that the number of
      sessions with CI >= 0.5 correlated with the change in the FMA scores. This
      suggests that post-stroke motor recovery best results from the activation in the
      lesion hemisphere, which is in agreement with previous studies performed using
      multimodal imaging technologies. 

PMID- 24109676
TI  - Brain-computer interface supported collaborative work: Implications for
      rehabilitation.
AB  - Working together and collaborating in a group can provide greater benefits for
      people with severe motor disability. However, it is still not clear how
      collaboration should be supported by BCI systems. The present study explored BCI
      supported collaborative work by investigating differences in performance and
      brain activity between when a pair of users performs a task jointly with each
      other and when they do alone only through means of their brain activity. We found
      differences in performance and brain activity between different work conditions.
      The results of this research should provide fundamental knowledge of BCI
      supported cooperative work. 

PMID- 24109675
TI  - Functional recovery in upper limb function in stroke survivors by using brain
      computer interface A single case A-B-A-B design.
AB  - Resent studies suggest that brain-computer interface (BCI) training for chronic
      stroke patient is useful to improve their motor function of paretic hand.
      However, these studies does not show the extent of the contribution of the BCI
      clearly because they prescribed BCI with other rehabilitation systems, e.g. an
      orthosis itself, a robotic intervention, or electrical stimulation. We therefore
      compared neurological effects between interventions with neuromuscular electrical
      stimulation (NMES) with motor imagery and BCI-driven NMES, employing an ABAB
      experimental design. In epoch A, the subject received NMES on paretic extensor
      digitorum communis (EDC). The subject was asked to attempt finger extension
      simultaneously. In epoch B, the subject received NMES when BCI system detected
      motor-related electroencephalogram change while attempting motor imagery. Both
      epochs were carried out for 60 min per day, 5 days per week. As a result, EMG
      activity of EDC was enhanced by BCI-driven NMES and significant cortico-muscular
      coherence was observed at the final evaluation. These results indicate that the
      training by BCI-driven NMES is effective even compared to motor imagery combined
      with NMES, suggesting the superiority of closed-loop training with BCI-driven
      NMES to open-loop NMES for chronic stroke patients. 

PMID- 24109677
TI  - Treatment effectiveness of brain-computer interface training for patients with
      focal hand dystonia: A double-case study.
AB  - Neuronal mechanism underlying dystonia is poorly understood. Dystonia can be
      treated with botulinum toxin injections or deep brain stimulation but these
      methods are not available for every patient therefore we need to consider other
      methods Our study aimed to develop a novel rehabilitation training using brain
      computer interface system that decreases neural overexcitation in the
      sensorimotor cortex by bypassing brain and external world without the normal
      neuromuscular pathway. To achieve this purpose, we recorded electroencephalograms
      (10 channels) and forearm electromyograms (3 channels) from 2 patients with the
      diagnosis of writer's cramp and healthy control participants as a preliminary
      experiment. The patients were trained to control amplitude of their
      electroencephalographic signal using feedback from the brain-computer interface
      for 1 hour a day and then continued the training twice a month. After the 5-month
      training, a patient clearly showed reduction of dystonic movement during writing.

PMID- 24109678
TI  - Specifications of an electromyogram-driven neuromuscular stimulator for upper
      limb functional recovery.
AB  - An electromyogram (EMG)-driven neuromuscular stimulator for upper limb functional
      recovery (Muraoka et al., 1998) can stimulate target muscles in proportion to the
      amount of voluntary EMG of the identical target muscles. Furthermore, it can
      facilitate the contraction of paralyzed muscles by electrical stimulation at
      subthreshold intensity level. Although it has been suggested that to use the
      stimulator for as long a time as possible might be needed for more effective
      treatment, the utilization time was limited by the size of the stimulator, which
      involved a laptop personal computer. To use in daily life, the device was
      improved to be a smaller size of 95*65*40 mm (including batteries) which was
      equivalent to a mobile phone (in 2002). The stimulator was called the Integrated
      Volitional-control Electrical Stimulator (IVES). IVES has already been
      manufactured and its use has spread in Japan since 2008. Nowadays, therapy using
      IVES is an effective therapy to improve the motor function of the upper limb in
      post-stroke patients with hemiparesis. However, the signal processing and
      internal structure of IVES has not yet been reported. In this study the device
      specification of IVES is described, especially its electrical circuits and signal
      processing that detect voluntary EMG and stimulate from the same electrodes. IVES
      uses two DIACs for detecting voluntary EMG from stimulating electrodes. The DIACs
      switch passively between the stimulation circuit and the EMG amplifier circuit.
      Furthermore, the signal processing of the time-shifted difference of the 2-cycle
      EMG signal following identical stimulation pulses eliminates stimulation
      artifacts and evoked potentials, and extracts voluntary EMG.

PMID- 24109679
TI  - Is event-related desynchronization a biomarker representing corticospinal
      excitability?
AB  - Brain computer interfaces (BCIs) using event-related desynchronization (ERD) of
      the electroencephalogram (EEG), which is believed to represent increased
      activation of the sensorimotor cortex, have attracted attention as tools for
      rehabilitation of upper limb motor functions in hemiplegic stroke patients.
      However, it remains unclear whether the corticospinal excitability is actually
      correlated with ERD. The purpose of this study was to assess the association
      between the ERD magnitude and the excitability of primary motor cortex (M1) and
      spinal motoneurons. M1 excitability was tested by motor evoked potentials (MEPs),
      short-interval intracortical inhibition (SICI) and intracortical facilitation
      (ICF) using transcranial magnetic stimulation, and spinal motoneuronal
      excitability was tested by F-waves using peripheral nerve stimulation. Results
      showed that large ERD during motor imagery was associated with significantly
      increased F-wave persistence and reduced SICI, but no significant changes in ICF
      and the response average of F-wave amplitudes. Our findings suggest that ERD
      magnitude during motor imagery represents the instantaneous excitability of both
      M1 and spinal motoneurons. This study provides electrophysiological evidence that
      ERD-based BCI with motor imagery task increases corticospinal excitability as
      changes accompanying actual movements. 

PMID- 24109680
TI  - Brain-machine interface control using broadband spectral power from local field
      potentials.
AB  - Recent progress in brain-machine interfaces (BMIs) has shown tremendous
      improvements in task complexity and degree of control. In particular, closed-loop
      decoder adaptation (CLDA) has emerged as an effective paradigm for both improving
      and maintaining the performance of BMI systems. Here, we demonstrate the first
      reported use of a CLDA algorithm to rapidly achieve high-performance control of a
      BMI based on local field potentials (LFPs). We trained a non-human primate to
      control a 2-D computer cursor by modulating LFP activity to perform a center-out
      reaching task, while applying CLDA to adaptively update the decoder. We show that
      the subject is quickly able to readily reach and hold at all 8 targets with an
      average success rate of 74% +/- 7% (sustained peak rate of 85%), with rapid
      convergence in the decoder parameters. Moreover, the subject is able to maintain
      high performance across 4 days with minimal adaptations to the decoder. Our
      results indicate that CLDA can be used to facilitate LFP-based BMI systems,
      allowing for both rapid improvement and maintenance of performance. 

PMID- 24109681
TI  - Utilizing movement synergies to improve decoding performance for a brain machine
      interface.
AB  - A major challenge facing the development of high degree of freedom (DOF) brain
      machine interface (BMI) devices is a limited ability to provide prospective users
      with independent control of many DOFs when using a complex prosthesis. It has
      been previously shown that a large range of complex hand postures can be
      replicated using a relatively low number of movement synergies. Thus, a high DOF
      joint space, such as the one the hand resides in, may be decomposed via principal
      component analysis (PCA) into a lower DOF (eigen-reach) space that contains most
      of the variance of the original movements. By decoding in this eigen-reach space,
      BMI users need only control a few eigen-reach values to be able to make movements
      using all DOFs in the arm and hand. In this paper we examine how using PCA before
      decoding neural activity may lead to improvements in decoding performance. 

PMID- 24109682
TI  - Investigating the role of firing-rate normalization and dimensionality reduction
      in brain-machine interface robustness.
AB  - The intraday robustness of brain-machine interfaces (BMIs) is important to their
      clinical viability. In particular, BMIs must be robust to intraday perturbations
      in neuron firing rates, which may arise from several factors including recording
      loss and external noise. Using a state-of-the-art decode algorithm, the
      Recalibrated Feedback Intention Trained Kalman filter (ReFIT-KF) we introduce two
      novel modifications: (1) a normalization of the firing rates, and (2) a reduction
      of the dimensionality of the data via principal component analysis (PCA). We
      demonstrate in online studies that a ReFIT-KF equipped with normalization and PCA
      (NPC-ReFIT-KF) (1) achieves comparable performance to a standard ReFIT-KF when at
      least 60% of the neural variance is captured, and (2) is more robust to the
      undetected loss of channels. We present intuition as to how both modifications
      may increase the robustness of BMIs, and investigate the contribution of each
      modification to robustness. These advances, which lead to a decoder achieving
      state-of-the-art performance with improved robustness, are important for the
      clinical viability of BMI systems.

PMID- 24109683
TI  - Direction and speed tuning of motor-cortex multi-unit activity and local field
      potentials during reaching movements.
AB  - Primary motor-cortex multi-unit activity (MUA) and local-field potentials (LFPs)
      have both been suggested as potential control signals for brain-computer
      interfaces (BCIs) aimed at movement restoration. Some studies report that LFP
      based decoding is comparable to spiking-based decoding, while others offer
      contradicting evidence. Differences in experimental paradigms, tuning models and
      decoding techniques make it hard to directly compare these results. Here, we use
      regression and mutual information analyses to study how MUA and LFP encode
      various kinematic parameters during reaching movements. We find that in addition
      to previously reported directional tuning, MUA also contains prominent speed
      tuning. LFP activity in low-frequency bands (15-40Hz, LFPL) is primarily speed
      tuned, and contains more speed information than both high-frequency LFP (100
      300Hz, LFPH) and MUA. LFPH contains more directional information compared to
      LFPL, but less information when compared with MUA. Our results suggest that a
      velocity and speed encoding model is most appropriate for both MUA and LFPH,
      whereas a speed only encoding model is adequate for LFPL. 

PMID- 24109684
TI  - Operant conditioning of a multiple degree-of-freedom brain-machine interface in a
      primate model of amputation.
AB  - Operant conditioning with biofeedback has been shown to be an effective method to
      modify neural activity to generate goal-directed actions in a brain-machine
      interface. It is particularly useful when neural activity cannot be
      mathematically mapped to motor actions of the actual body such as in the case of
      amputation. Here, we implement an operant conditioning approach with visual
      feedback in which an amputated monkey is trained to control a multiple degree-of
      freedom robot to perform a reach-to-grasp behavior. A key innovation is that each
      controlled dimension represents a behaviorally relevant synergy among a set of
      joint degrees-of-freedom. We present a number of behavioral metrics by which to
      assess improvements in BMI control with exposure to the system. The use of non
      human primates with chronic amputation is arguably the most clinically-relevant
      model of human amputation that could have direct implications for developing a
      neural prosthesis to treat humans with missing upper limbs. 

PMID- 24109685
TI  - Long-term, stable behavior of local field potentials during brain machine
      interface use.
AB  - Local field potentials (LFPs) have the potential to provide robust, long-lasting
      control signals for brain-machine interfaces (BMIs). Moreover, they have been
      hypothesized to be a stable signal source. Here we assess the long-term stability
      of LFPs and multi-unit spikes (MSPs) in two monkeys using both LFP-based and MSP
      based, biomimetic BMIs to control a computer cursor. The monkeys demonstrated
      highly accurate performance using both the LFP- and MSP-based BMIs. This
      performance remained high for 11 and 6 months, respectively, without adapting or
      retraining. We evaluated the stability of the LFP features and MSPs themselves by
      building, in each session, linear decoders of the BMI-controlled cursor velocity
      using single features or single MSPs. We then used these single-feature decoders
      to decode BMI-controlled cursor velocity in the last session. Many of the LFP
      features and MSPs showed stably-high correlations with the cursor velocity over
      the entire study period. This implies that the monkeys were able to maintain a
      stable mapping between either motor cortical field potentials or multi-spike
      potentials and BMI-controlled outputs. 

PMID- 24109687
TI  - 3D fabrication of biological machines.
AB  - Cell-based biological machines can be defined as a set of sub-components
      consisting of living cells and cell-instructive micro-environments that interact
      to perform a range of prescribed tasks. The realization of biological machines
      and their sub-components will require a number of suitable cell sources,
      biomaterials, and enabling technologies. Here, we review our group's recent
      accomplishments and continuing efforts toward the development of building
      biological machines. 

PMID- 24109688
TI  - Self-oscillating polymer gels as novel biomimetic materials.
AB  - Stimuli-responsive polymer gels and their application to smart materials have
      been widely studied. On the other hand, as a novel biomimetic gel, we developed
      gels with an autonomous self-oscillating function like a heart muscle, which was
      firstly reported in 1996. We designed the self-oscillating polymers and gels by
      utilizing the oscillating reaction, called the Belousov-Zhabotinsky (BZ) reaction
      as a chemical model of the TCA cycle. The self-oscillating polymer is composed of
      a poly(N-isopropylacrylamide) network in which the metal catalyst for the BZ
      reaction is covalently bonded. In a closed solution containing the reactants
      other than the catalyst, the polymer gel undergoes spontaneous cyclic swelling
      deswelling changes without any on-off switching of external stimuli. Their
      potential applications include several kinds of functional material systems, such
      as biomimetic actuators and mass transport surface. Here recent progress on the
      novel polymer gels is introduced. 

PMID- 24109689
TI  - Enhanced differentiation of rat MSCs into cardiomyocytes with 5
      azacytidine/collagen I nano-molecules.
AB  - This study was to investigate the enhancement ability of 5-azacytidine (5-aza)
      and collagen I nano-molecules treatment to the differentiation of rat mesenchymal
      stem cells (MSCs) towards a cardiomyocytes in vitro. The results demonstrated
      that the size of the cells increased significantly and connecting with adjoining
      cells by forming myotube-like structures. Also, additional treatment of the MSCs
      with collagen I nano-fibrils significantly increased two transcription factors
      GATA-4 and Nkx2.5 expressions and three expressions of cardiac genes of troponin
      I, beta-myosin heavy chain and cardiac alpha-actin compared with MSC groups
      treated only with 5-aza at early 3 d culturing(all, P<0.01 or better). These
      results indicate that culturing MSCs with collagen I nano-molecules, which could
      act as scaffolds or soluble protein ingredients, leads to alterations in gene
      expression and affects the differentiation fate induced with 5-aza. 

PMID- 24109690
TI  - Engineered muscle systems having individually addressable distributed muscle
      actuators controlled by optical stimuli.
AB  - A multi degree-of-freedom system using live skeletal muscles as actuators is
      presented. Millimeter-scale, optically excitable 3D skeletal muscle strips are
      created by culturing genetically coded precursory muscle cells that are activated
      with light: optogenetics. These muscle bio-actuators are networked together to
      create a distributed actuator system. Unlike traditional mechanical systems where
      fixed axis joints are rotated with electric motors, the new networked muscle bio
      actuators can activate loads having no fixed joint. These types of loads include
      shoulders, the mouth, and the jaw. The optogenetic approach offers high
      spatiotemporal resolution for precise control of muscle activation, and opens up
      the possibility to activate hundreds of interconnected muscles in a
      spatiotemporally coordinated manner. In this work, we explore the design of
      robotic systems composed of multiple light-activated live muscular actuator
      units. We describe and compare massively parallel and highly serial/networked
      distributions of these building-block actuator units. We have built functional
      fundamental prototypes and present experimental results to demonstrate the
      feasibility of the construction of larger scale muscle systems. 

PMID- 24109691
TI  - Development of control model for intelligently controllable ankle-foot orthosis.
AB  - We have developed an intelligently controllable ankle-foot orthosis (i-AFO). In
      this paper, we formulated a new control method for the i-AFO. In the method the
      sensor system of the i-AFO estimates walking speed of user and decide optimal
      drop speed of foot at the duration between initial contact and foot flat. We
      conducted the pretest for eight healthy subjects to make a control rule for the
      drop speed. Then we conducted the modeling test for one patient to make an
      estimation rule for walking speed. Finally we conducted the evaluation test for
      the proposed method. Despite the walking speed estimation show errors, the i-AFO
      successfully controlled the foot motion depending on the gait states. 

PMID- 24109692
TI  - Control of wearable motion assist robot for upper limb based on the equilibrium
      position estimation.
AB  - In this paper, we propose a robotic system for assisting patients who have upper
      limb dysfunction in performing reaching movements through flexion. Since upper
      limb motion is more strongly needed than lower limb mobility for near work, a
      patient's level of recovery of upper limb function influences daily life.
      Recently, with the widespread application of robotic technology in rehabilitation
      medicine, active movement has often been noted to be more important than passive
      movement for rapid recovery. A novel control method for assisting upper limb
      movement by using a control system with two degrees of freedom is proposed. In
      the process of estimating the trajectory, the minimum jerk criterion is used to
      compute the velocity trajectory and to determine the reach position. The aim is
      to eventually develop a movement assistance system for the upper limb which will
      enable wearers to perform flexion and extension covering ranges of motion which
      are otherwise impossible to achieve autonomously. The effectiveness of the
      developed system is demonstrated experimentally. 

PMID- 24109693
TI  - Control of an optimal finger exoskeleton based on continuous joint angle
      estimation from EMG signals.
AB  - Patients suffering from loss of hand functions caused by stroke and other spinal
      cord injuries have driven a surge in the development of wearable assistive
      devices in recent years. In this paper, we present a system made up of a low
      profile, optimally designed finger exoskeleton continuously controlled by a
      user's surface electromyographic (sEMG) signals. The mechanical design is based
      on an optimal four-bar linkage that can model the finger's irregular trajectory
      due to the finger's varying lengths and changing instantaneous center. The
      desired joint angle positions are given by the predictive output of an artificial
      neural network with an EMG-to-Muscle Activation model that parameterizes
      electromechanical delay (EMD). After confirming good prediction accuracy of
      multiple finger joint angles we evaluated an index finger exoskeleton by
      obtaining a subject's EMG signals from the left forearm and using the signal to
      actuate a finger on the right hand with the exoskeleton. Our results show that
      our sEMG-based control strategy worked well in controlling the exoskeleton,
      obtaining the intended positions of the device, and that the subject felt the
      appropriate motion support from the device. 

PMID- 24109694
TI  - NEUROExos: A powered elbow orthosis for post-stroke early neurorehabilitation.
AB  - This paper presents the development of a portable version of the robotic elbow
      exoskeleton NEUROExos, designed for the treatment of stroke survivors in
      acute/sub-acute phases. The design was improved by a novel Series Elastic
      Actuation (SEA) system. The system implements two control modalities: a near-zero
      output impedance torque control and a passive-compliance position control. 

PMID- 24109695
TI  - Development of a smart backboard system for real-time feedback during CPR chest
      compression on a soft back support surface.
AB  - The quality of cardiopulmonary resuscitation (CPR) is often inconsistent and
      frequently fails to meet recommended guidelines. One promising approach to
      address this problem is for clinicians to use an active feedback device during
      CPR. However, one major deficiency of existing feedback systems is that they fail
      to account for the displacement of the back support surface during chest
      compression (CC), which can be important when CPR is performed on a soft surface.
      In this study we present the development of a real-time CPR feedback system based
      on an algorithm which uses force and dual-accelerometer measurements to provide
      accurate estimation of the CC depth on a soft surface, without assuming full
      chest decompression. Based on adult CPR manikin tests it was found that the
      accuracy of the estimated CC depth for a dual accelerometer feedback system is
      significantly better (7.3% vs. 24.4%) than for a single accelerometer system on
      soft back support surfaces, in the absence or presence of a backboard. In
      conclusion, the algorithm used was found to be suitable for a real-time, dual
      accelerometer CPR feedback application since it yielded reasonable accuracy in
      terms of CC depth estimation, even when used on a soft back support surface. 

PMID- 24109696
TI  - Development of a diagnostic glove for unobtrusive measurement of chest
      compression force and depth during neonatal CPR.
AB  - Optimizing chest compression (CC) performance during neonatal cardiopulmonary
      resuscitation (CPR) is critical to improving survival outcomes since current
      clinical protocols often achieve only a fraction of the native cardiovascular
      perfusion. This study presents the development of a diagnostic tool to
      unobtrusively measure the CC depth and force during neonatal CPR using sensors
      mounted on a glove platform. The performance of the glove was evaluated by infant
      manikin tests using the two-thumb (TT) and two-finger (TF) methods of CC during
      simulated, unventilated neonatal CPR. The TT method yielded maximum CC depths and
      forces of as much as 25.7 +/- 3.2 mm and 35.9 +/- 2.2 N while the TF method
      produced CC depths and forces of as much as 21.6 +/- 2.2 mm and 23.7 +/- 2.9 N.
      These results are consistent with clinical findings which suggest that TT
      compression is more effective than TF compression since it produces greater CC
      depths and forces. 

PMID- 24109697
TI  - Health technology assessment to improve the medical equipment life cycle
      management.
AB  - Health technology assessment (HTA) is a tool to support decision making that is
      intended to assist healthcare managers in their strategic decisions. The use of
      HTA as a tool for clinical engineering is especially relevant in the domain of
      the medical equipment once it could improve the performance of the medical
      equipment. It would be done by their systematically evaluation in several
      aspects, in their life cycle. In Brazil, the Institute of Biomedical Engineering
      (IEB-UFSC) through the clinical engineering area has been working on the
      development of methodologies and improvements on HTA for medical equipment.
      Therefore, this paper presents the effort to create specific methodologies that
      will improve the dissemination of HTA, focusing on incorporation and utilization
      phase of the medical equipment life cycle. This will give a better support to the
      decision makers in the management of the health care system. 

PMID- 24109698
TI  - Development of automated 3-dimensional tissue fabrication system Tissue Factory -
      Automated cell isolation from tissue for regenerative medicine.
AB  - We have developed a new automated cell isolation system as one of the modules of
      automated cell sheet production system named Tissue-Factory (T-Factory). This
      system enables isolation of the target cells from tissue. Using this new system,
      we successfully isolated skeletal myoblast from skeletal muscle tissue. The cell
      isolation system makes us stably prepare cell suspension from each tissue
      automatically and safely. Isolation of skeletal myoblasts will contribute to
      labor-saving cell cultivation and operational stability, and lead further process
      in tissue engineering and regenerative medicine. 

PMID- 24109699
TI  - Lower limb examinations for muscular tension estimation methods for each muscle
      group based on functionally different effective muscle theory.
AB  - Conventional estimation methods distribute tension to muscles by solving
      optimization problems, because the system is redundant. The theory of
      functionally different effective muscle, based on 3 antagonistic pairs of muscle
      groups in limbs, has enabled to calculate the maximum joint torque of each pair,
      i.e. functionally different effective muscle force. Based on this theory, a
      method to estimate muscular tension has been proposed, where joint torque of each
      muscle group is derived by multiplying functionally different effective muscle
      force, the muscular activity of muscular activity pattern for direction of tip
      force, and ratio of tip force to maximum output force. The estimation of this
      method is as good as Crowninshield's method, moreover this method also reduce the
      computation time if the estimation concerns a selected muscle group. 

PMID- 24109700
TI  - Anthropometric body measurements based on multi-view stereo image reconstruction.
AB  - Anthropometric measurements, such as the circumferences of the hip, arm, leg and
      waist, waist-to-hip ratio, and body mass index, are of high significance in
      obesity and fitness evaluation. In this paper, we present a home based imaging
      system capable of conducting anthropometric measurements. Body images are
      acquired at different angles using a home camera and a simple rotating disk.
      Advanced image processing algorithms are utilized for 3D body surface
      reconstruction. A coarse body shape model is first established from segmented
      body silhouettes. Then, this model is refined through an inter-image consistency
      maximization process based on an energy function. Our experimental results using
      both a mannequin surrogate and a real human body validate the feasibility of the
      proposed system. 

PMID- 24109701
TI  - An image guided treatment platform for prostate cancer photodynamic therapy.
AB  - This study describes a multimodality images based platform to drive photodynamic
      therapies of prostate cancer using WST 11 TOOKAD Soluble drug. The platform
      integrates a pre-treatment planning tool based on magnetic resonance imaging and
      a per-treatment guidance tool based on transrectal ultrasound images. Evaluation
      of the platform on clinical data showed that prediction of the therapy outcome
      was possible with an accuracy of 90 %. 

PMID- 24109702
TI  - Optical diagnostic and therapy applications of femtosecond laser radiation using
      lens-axicon focusing.
AB  - Diagnostic modalities by means of optical and/or near infrared femtosecond
      radiation through biological media can in principle be adapted to therapeutic
      applications. Of specific interest are soft tissue diagnostics and subsequent
      therapy through hard tissue such as bone. Femto-second laser pulses are delivered
      to hydroxyapatite representing bone, and photo-acoustic spectroscopy is presented
      in order to identify the location of optical anomalies in an otherwise
      homogeneous medium. Imaging through bone is being considered for diagnostic, and
      potentially therapeutic, applications related to brain tumors. The use of
      mesomeric optics such as lens-axicon combinations is of interest to achieve the
      favorable distribution of focused radiation. Direct therapy by increasing local
      temperature to induce hyperthermia is one mode of brain tumor therapy. This can
      be enhanced by seeding the tumor with nanoparticles. Opto-acoustic imaging using
      femtosecond laser radiation is a further opportunity for diagnosis. 

PMID- 24109703
TI  - Monitoring of temperature increase and tissue vaporization during laser
      interstitial thermotherapy of ex vivo swine liver by computed tomography.
AB  - Laser interstitial thermotherapy (LITT) is a minimally invasive technique used to
      thermally destroy tumour cells. Being based on hyperthermia, LITT outcome depends
      on the temperature distribution inside the tissue. Recently, CT scan thermometry,
      based on the dependence of the CT number (HU) on tissue temperature (T) has been
      introduced during LITT; it is an attractive approach to monitor T because it
      overcomes the concerns related to the invasiveness. We performed LITT on nine ex
      vivo swine livers at three different laser powers, (P=1.5 W, P=3 W, P=5 W) with a
      constant treatment time t=200 s; HU is averaged on two ellipsoidal regions of
      interest (ROI) of 0.2 cm2, placed at two distances from the applicator (d=3.6 mm
      and d=8.7 mm); a reference ROI was placed away from the applicator (d=30 mm). The
      aim of this study is twofold: 1) to evaluate the effect of the T increase in
      terms of HU variation in ex vivo swine livers undergoing LITT; and 2) to estimate
      the P value for tissue vaporization. To the best of our knowledge, this is the
      first study focused on the HU variation in swine livers undergoing LITT at
      different P. The reported findings could be useful to assess the effect of LITT
      on the liver in terms of both T changes and tissue vaporization, with the aim to
      obtain an effective therapy.

PMID- 24109704
TI  - Derivation of the relationship between the rate of temperature rise and
      viscoelasticity for constructing a coagulation model for liver radio frequency
      ablation.
AB  - Radio frequency ablation (RFA) is usually conducted using ultrasound (US) imaging
      to monitor the insertion procedure and the coagulation extent of liver tissue
      which is contiguous to the RFA electrode. However, when RFA surgery is started,
      the US image becomes unclear because of water vapor. This disadvantage of RFA can
      lead to excessive and insufficient RFA thereby diminishing the advantages of the
      procedure. In the present study, we proposed a simulation system which shows the
      progress status of coagulation for liver RFA. To derive the coagulation
      characteristics in liver RFA, we used the viscoelasticity of liver tissue as the
      coagulation indicator to investigate coagulation development for liver RFA. This
      paper shows the acquisition procedures for analyzing the relationship between the
      rate of temperature and viscoelasticity. We measured the complex modulus of
      porcine liver tissue under different rate of temperature in RFA by controlling
      the output power. We showed that the viscoelasticity of liver tissue depended on
      temperature previous temperature increase above 60 degrees C. This result
      indicates that in RFA, controlling the output power is important to completely
      coagulate the tumor. 

PMID- 24109705
TI  - The relation between temperature distribution for lung RFA and electromagnetic
      wave frequency dependence of electrical conductivity with changing a lung's
      internal air volumes.
AB  - Radio frequency ablation (RFA) for lung cancer has increasingly been used over
      the past few years because it is a minimally invasive treatment. As a feature of
      RFA for lung cancer, lung contains air during operation. Air is low thermal and
      electrical conductivity. Therefore, RFA for this cancer has the advantage that
      only the cancer is coagulated, and it is difficult for operators to control the
      precise formation of coagulation lesion. In order to overcome this limitation, we
      previously proposed a model-based robotic ablation system using finite element
      method. Creating an accurate thermo physical model and constructing thermal
      control method were a challenging problem because the thermal properties of the
      organ are complex. In this study, we measured electromagnetic wave frequency
      dependence of lung's electrical conductivity that was based on lung's internal
      air volumes dependence with in vitro experiment. In addition, we validated the
      electromagnetic wave frequency dependence of lung's electrical conductivity using
      temperature distribution simulator. From the results of this study, it is
      confirmed that the electromagnetic wave frequency dependence of lung's electrical
      conductivity effects on heat generation of RFA. 

PMID- 24109706
TI  - Real-time temperature control system based on the finite element method for liver
      radiofrequency ablation: effect of the time interval on control.
AB  - Radiofrequency (RF) ablation is increasingly being used to treat liver cancer
      because it is minimally invasive. However, it is difficult for operators to
      control the size of the coagulation zones precisely, because no method has been
      established to form an adequate and suitable ablation area. To overcome this
      limitation, we propose a new system that can control the coagulation zone size.
      The system operates as follows: 1) the liver temperature is estimated using a
      temperature-distribution simulator to reduce invasiveness; 2) the output power of
      the RF generator is controlled automatically according to the liver temperature.
      To use this system in real time, both the time taken to calculate the temperature
      in the simulation and the control accuracy are important. We therefore
      investigated the relationship between the time interval required to change the
      output voltage and temperature control stability in RF ablation. The results
      revealed that the proposed method can control the temperature at a point away
      from the electrode needle to obtain the desired ablation size. It was also shown
      to be necessary to reduce the time interval when small tumors are cauterized to
      avoid excessive treatment. In contrast, such high frequency feedback control is
      not required when large tumors are cauterized. 

PMID- 24109707
TI  - Synthetic octacalcium phosphate: a possible carrier for mesenchymal stem cells in
      bone regeneration.
AB  - The present paper reviews biomaterial studies of synthetic octacalcium phosphate
      (OCP) as a scaffold of osteoblastic cells. OCP crystals have been suggested to be
      one of precursor phases in hydroxyapatite (HA) crystal formation in bone and
      tooth. The recent intensive biomaterials and tissue engineering studies using
      synthetic OCP disclosed the potential function of OCP as a bioactive material as
      well as synthetic HA materials due to its highly osteoconductive and
      biodegradable properties. In vitro studies showed that OCP crystals exhibit a
      positive effect on osteoblastic cell differentiation. In vivo studies confirmed
      that the materials of OCP in a granule forms and OCP-based composite materials
      with natural polymers, such as gelatin and collagen, enhance bone regeneration if
      implanted in various model bone defects with critical-sized diameters, defined as
      a defect which does not heal spontaneously throughout the lifetime of the
      animals. One of particular characteristics of OCP, found as a mechanism to
      enhance bone regeneration in vivo, is a process of progressive conversion from
      OCP to HA at physiological conditions. The OCP-HA conversion is accompanied by
      progressive physicochemical changes of the material properties, which affects the
      tissue reaction around the crystals where osteoblastic cells are encountered.
      Mesenchymal stem cells (MSCs) seeded in an OCP-based material enhanced bone
      regeneration in the rat critical-sized calvaria defect more than that by the
      material alone. The overall results reveal that OCP crystals have an effect on
      osteoblastic cell differentiation including the differentiation of MSCs in vivo.
      The evidence collected experimentally in the laboratory was presented. 

PMID- 24109708
TI  - Frictional properties of articular cartilage-like tissues repaired with a
      mesenchymal stem cell-based tissue engineered construct.
AB  - We have been developing a novel tissue engineering technique for cartilage repair
      using a scaffold-free tissue engineered construct (TEC) bio-synthesized from
      synovium-derived mesenchymal stem cells (MSCs). In the present study, the effect
      of TEC on the repair of chondral defect in the femoral condyle of immature and
      mature pigs were investigated. The permeability of TEC-treated repaired tissues
      was significantly higher than normal level at surface layer in immature animals,
      while the permeability was slightly higher than normal level at middle and deep
      layers in mature animals. In immature animals, the coefficient of friction of TEC
      treated tissues against a glass plate was load-dependently increased, with a
      significantly higher value than normal level observed at a high load (280 kPa).
      In contrast, the coefficient of friction was load-dependently decreased in mature
      animals, with no significant differences from normal level observed at all loads
      (70, 140, and 280 kPa). It is suggested that the frictional properties of TEC
      treated cartilage-like repaired tissues are recovered to normal level in mature
      animals, while they are unrecovered to normal level due to underdeveloped,
      permeable surface layer in immature animals. 

PMID- 24109709
TI  - How do chondrocytes aggregate on fibroin substrate.
AB  - The effects of substrate material on the spatio-temporal behavior of cells is an
      important issue. Although cell aggregation has been observed on various fibroin
      substrates, the mechanisms of this aggregation have yet to be fully clarified. In
      this study, cell aggregation behavior on fibroin substrates were evaluated,
      focusing on the distance between each cell and the direction of individual cell
      migration. Our results showed that on fibroin substrates cells did not attract
      each other. However cells stayed close to adjacent cells over 24 hours of
      cultivation. 

PMID- 24109710
TI  - In vitro bone formation by mesenchymal stem cells with 3D collagen/beta-TCP
      composite scaffold.
AB  - Recent years, various kinds of natural polymers and bioceramics has been used to
      develop porous scaffolds for bone tissue engineering. Among of them, collagen
      guarantees good biological conditions, and beta-tricalcium phosphate (beta-TCP)
      possesses good oseteoconductivity, cellular adhesion, accelerated differentiation
      and mechanical property. In this study, rat bone marrow mesenchymal stem cells
      (rMSC) were cultured in beta-TCP/collagen composite scaffolds up to 28 days in
      order to assess the time-dependent behavior of the extracellular matrix formation
      and the mechanical performance of the scaffold-cell system. The cell number and
      ALP activity were evaluated using a spectrophotometric plate reader. Gene
      expression of osteogenesis was analyzed using the real-time PCR reactions.
      Compression tests were also conducted periodically by using a conventional
      testing machine to evaluate the elastic modulus. The increasing behaviors of cell
      number and ALP activity in the composite scaffold were much better than in the
      collagen scaffold. The gene expression of osteocalcin and collagen type-I in
      collagen/beta-TCP scaffold was higher than that of the collagen scaffold. The
      compressive modulus also increased up to 28 days. These results clearly showed
      that the distribution of micro beta-TCP particles is very effective to increase
      the elastic modulus and promote cell growth.

PMID- 24109711
TI  - An approach to absence epileptic seizures detection using Approximate Entropy.
AB  - Epilepsy is one of the most common chronic neurological diseases and the most
      common neurological chronic disease of childhood. The electroencephalogram (EEG)
      signal provides significant information neurologists take into consideration in
      the investigation and analysis of epileptic seizures. The Approximate Entropy
      (ApEn) is a formulated statistical parameter commonly used to quantify the
      regularity of a time series data of physiological signals. In this paper ApEn is
      used in order to detect the onset of epileptic seizures. The results show that
      the method provides promising results towards efficient detection of onset and
      ending of seizures, based on analyzing the corresponding EEG signals. ApEn
      parameters affect the method's behavior, suggesting that a more detailed study
      and a consistent methodology of their determination should be established. A
      preliminary analysis for the proper determination of these parameters is
      performed towards improving the results. 

PMID- 24109712
TI  - Tracking non-stationary spectral peak structure in EEG data.
AB  - We develop a particle filter algorithm to simultaneously estimate and track the
      instantaneous peak frequency, amplitude, and bandwidth of multiple concurrent non
      stationary components of an EEG signal in the time-frequency domain. We use this
      method to characterize human EEG activity during anesthesia-induced
      unconsciousness. 

PMID- 24109713
TI  - The effect of applying orthogonal projection technique in short window segments
      to obtain fetal magnetocardiogram.
AB  - Non-invasive recordings of fetal heart and brain have been possible for almost a
      decade with the advancement in biomagnetic sensors using the SQUID
      (Superconducting Quantum Interference Device) technology. Techniques such as
      orthogonal projection and ICA have been applied to attenuate interference from
      other biological sources such as maternal heart. Successful application of such
      techniques among other factors depend on the non-stationary characteristics of
      the signals. To minimize the effect of non-stationarity due to maternal and/or
      fetal movement in long duration datasets, we proposed to investigate the minimal
      time window that is needed to obtain averaging with good SNR to apply the
      orthogonal projection technique to attenuate maternal magnetocardiogram (MCG) and
      obtain fetal MCG. The quantifying measure is based on spectral power of signals
      from 151-channel SQUID array system. 

PMID- 24109714
TI  - Motion artifact suppression in the ECG signal by successive modifications in
      frequency and time.
AB  - Ambulatory electrocardiogram signals can be contaminated with various types of
      noise. Among these, electrode motion 'em' artifacts are considered particularly
      undesired as they can be mistaken for ectopic beats. Unfortunately, 'em' noise
      has proved difficult to tackle using ordinary filtering techniques. In this
      paper, we explore a novel filtering alternative, and show that it could be
      considered as a potential candidate for dealing with electrode motion artifacts.
      The proposed system is composed of two simple parts: a frequency filter and a
      time window, interconnected in series. The two components are designed such that
      the overall system operates optimally in the mean square error sense.
      Experimentation on signals obtained from the MIT-BIH database demonstrates the
      superiority of the above approach over optimal Fourier filtering. 

PMID- 24109715
TI  - Feature consistency-based model adaptation in session-to-session classification:
      a study using motor imagery of swallow EEG signals.
AB  - The performance degradation for session to session classification in brain
      computer interface is a critical problem. This paper proposes a novel method for
      model adaptation based on motor imagery of swallow EEG signal for dysphagia
      rehabilitation. A small amount of calibration testing data is utilized to select
      the model catering for test data. The features of the training and calibration
      testing data are firstly clustered and each cluster is labeled by the dominant
      label of the training data. The cluster with the minimum impurity is selected and
      the number of features consistent with the cluster label are calculated for both
      training and calibration testing data. Finally, the training model with the
      maximum number of consistent features is selected. Experiments conducted on motor
      imagery of swallow EEG data achieved an average accuracy of 74.29% and 72.64%
      with model adaptation for Laplacian derivates of power features and wavelet
      features, respectively. Further, an average accuracy increase of 2.9% is achieved
      with model adaptation using wavelet features, in comparison with that achieved
      without model adaptation, which is significant at 5% significance level as
      demonstrated in the statistical test. 

PMID- 24109716
TI  - Design of an online EEG based neurofeedback game for enhancing attention and
      memory.
AB  - Brain-Computer Interface (BCI) is an alternative communication and control
      channel between brain and computer which finds applications in neuroprosthetics,
      brain wave controlled computer games etc. This paper proposes an
      Electroencephalogram (EEG) based neurofeedback computer game that allows the
      player to control the game with the help of attention based brain signals. The
      proposed game protocol requires the player to memorize a set of numbers in a
      matrix, and to correctly fill the matrix using his attention. The attention level
      of the player is quantified using sample entropy features of EEG. The
      statistically significant performance improvement of five healthy subjects after
      playing a number of game sessions demonstrates the effectiveness of the proposed
      game in enhancing their concentration and memory skills. 

PMID- 24109717
TI  - Normalized power variance change between pre-ictal and ictal phase of an epilepsy
      patient using NAT analysis: a case study.
AB  - Variance of state variables shifts due to phase-instability and may serve as an
      early-warning signal of phase transition of complex systems such as an epileptic
      seizure of brain cortical activity. Neuronal Activity Topology (NAT) analysis
      calculates a normalized-power-variance (NPV) of electroencephalogram (EEG) data
      in each frequency band to obtain relative values comparable among different power
      states. 

PMID- 24109718
TI  - Classification of iRBD and Parkinson's disease patients based on eye movements
      during sleep.
AB  - Patients suffering from the sleep disorder idiopathic rapid-eye-movement sleep
      behavior disorder (iRBD) have been observed to be in high risk of developing
      Parkinson's disease (PD). This makes it essential to analyze them in the search
      for PD biomarkers. This study aims at classifying patients suffering from iRBD or
      PD based on features reflecting eye movements (EMs) during sleep. A Latent
      Dirichlet Allocation (LDA) topic model was developed based on features extracted
      from two electrooculographic (EOG) signals measured as parts in full night
      polysomnographic (PSG) recordings from ten control subjects. The trained model
      was tested on ten other control subjects, ten iRBD patients and ten PD patients,
      obtaining a EM topic mixture diagram for each subject in the test dataset. Three
      features were extracted from the topic mixture diagrams, reflecting "certainty",
      "fragmentation" and "stability" in the timely distribution of the EM topics.
      Using a Naive Bayes (NB) classifier and the features "certainty" and "stability"
      yielded the best classification result and the subjects were classified with a
      sensitivity of 95 %, a specificity of 80% and an accuracy of 90 %. This study
      demonstrates in a data-driven approach, that iRBD and PD patients may exhibit
      abnorm form and/or timely distribution of EMs during sleep. 

PMID- 24109719
TI  - Feature selection for computerized fetal heart rate analysis using genetic
      algorithms.
AB  - During birth, timely and accurate diagnosis is needed in order to prevent severe
      conditions such as birth asphyxia. The fetal heart rate (FHR) is often monitored
      during labor to assess the condition of fetal health. Computerized FHR analysis
      is needed to help clinicians identify abnormal patterns and to intervene when
      necessary. The objective of this study is to apply Genetic Algorithms (GA) as a
      feature selection method to select a best feature subset from 64 FHR features and
      to integrate these best features to recognize unfavorable FHR patterns. The GA
      was trained on 408 cases and tested on 102 cases (both balanced datasets) using a
      linear SVM as classifier. 100 best feature subsets were selected according to
      different splits of data; a committee was formed using these best classifiers to
      test their classification performance. Fair classification performance was shown
      on the testing set (Cohen's kappa 0.47, proportion of agreement 73.58%). To our
      knowledge, this is the first time that a feature selection method has been tested
      for FHR analysis on a database of this size. 

PMID- 24109720
TI  - Estimation of the site of wheezes in pulmonary emphysema: airflow simulation
      study by the use of A 4D lung model.
AB  - Adventitious lung sounds in pulmonary emphysema, wheezes, are continuous musical
      sounds during expiration with 400 Hz or more. The textbook tells that expiratory
      airflow limitation in emphysema occurs at the peripheral airways and that wheezes
      are generated there. We have recently proposed a novel hypothesis based on image
      analysis and theoretical consideration that expiratory airflow limitation in
      emphysema occurs at the intra-mediastinal airway (trachea, main bronchi, and
      right lobar bronchi) due to compression by overinflated lungs. We performed
      expiratory airflow simulation by the use of a 4D finite element lung model, and
      found periodical vortex release with 300-900 Hz at the end of protrusion of the
      the tracheal posterior wall. Relationship between the peak frequency of pressure
      fluctuation and airflow velocity was in agreement with Strahal's law either in
      normal or emphysematous condition. Contrarily, airflow simulation in a small
      bronchus (1.5 mm in diameter) indicated no apparent periodic vortex release.

PMID- 24109721
TI  - 4D model generator of the human lung, "Lung4Cer".
AB  - We have developed a free software applications which generates 4D (= 3D + time)
      lung models for the purpose of studying lung anatomy, physiology, and
      pathophysiology. The coinage of 4C is originated from Japanese words, Catachi (=
      shape, structure) and Calacli (= machine, function). Lung4Cer makes 4D finite
      element models from the trachea to alveoli, which allow airflow simulation by
      means of computational fluid dynamics. Visualization of the generated models is
      expected to use a popular free software application, ParaView. There are several
      versions of Lung4Cer from basic lung morphology to advanced airflow computations
      simulating various clinical pulmonary function tests (PFT4Cer). All versions are
      designed so as to be operated on a common PC. Users can select model types and
      the element number according to their purposes and available computer resources. 

PMID- 24109722
TI  - Analysis of a dielectric EAP as smart component for a neonatal respiratory
      simulator.
AB  - Nowadays, respiratory syndrome represents the most common neonatal pathology.
      Nevertheless, being respiratory assistance in newborns a great challenge for
      neonatologists and nurses, use of simulation-based training is quickly becoming a
      valid meaning of clinical education for an optimal therapy outcome. Commercially
      available simulators, are, however, not able to represent complex breathing
      patterns and to evaluate specific alterations. The purpose of this work has been
      to develop a smart, lightweight, compliant system with variable rigidity able to
      replicate the anatomical behavior of the neonatal lung, with the final aim to
      integrate such system into an innovative mechatronic simulator device. A smart
      material based-system has been proposed and validated: Dielectric Electro Active
      Polymers (DEAP), coupled to a purposely shaped silicone camera, has been
      investigated as active element for a compliance change simulator able to
      replicate both physiological and pathological lung properties. Two different
      tests have been performed by using a bi-components camera (silicone shape coupled
      to PolyPower film) both as an isolated system and connected to an infant
      ventilator. By means of a pressure sensor held on the silicon structure, pressure
      values have been collected and compared for active and passive PolyPower working
      configuration. The obtained results confirm a slight pressure decrease in active
      configuration, that is in agreement with the film stiffness reduction under
      activation and demonstrates the real potentiality of DEAP for active volume
      changing of the proposed system. 

PMID- 24109723
TI  - Effects of the air sac thickness on ventilation by a 1D model of an avian
      respiratory system.
AB  - Airflow in an avian respiratory system was simulated to study why birds affected
      with airsacculitis have respiratory distress. The airflow in the avian lung was
      modeled with a 1D electrical circuit and simulated for investigating what effect
      an increase in wall thickness of air sacs caused by airsacculitis has on flow in
      lung. The results demonstrated that thickening of the air sac wall caused anti
      synchronization between an elastic recoiling force of the air sac walls and an
      intra-pleural pressure, bringing difficulties in expansion of air sacs to draw in
      airs during an inspiration period and thereby decreasing air to be pumped out
      during an expiration period. This was reflected in a decrease in air flow volume
      in parabronchi where gas exchange takes place. Therefore, it was concluded that
      airsacculitis causes imbalance in air flow dynamics in the avian lung and thus
      impairs breathing ability of birds. 

PMID- 24109724
TI  - A simple gas exchange model predicting arterial oxygen content for various FiO2
      levels.
AB  - The application of mechanical ventilation is a life-saving routine therapy that
      allows the patient to overcome the physiological impact of surgeries, trauma or
      critical illness by ensuring vital oxygenation and carbon dioxide removal. Above
      a certain level of minute ventilation (usually set to ensure acceptable carbon
      dioxide removal and oxygenation) oxygenation is only marginally affected by a
      further increase in minute ventilation. Thus, oxygenation is predominantly
      influenced by inspiratory oxygen fraction (FiO2) Usually, finding the appropriate
      setting is a trial-and-error procedure, as the clinician is unaware of the exact
      value that needs to be set in order to reach the desired arterial oxygen partial
      pressures (PaO2) in the patient. 

PMID- 24109725
TI  - A new method to increase the quality of cardiopulmonary resuscitation in
      hospital.
AB  - In order to ensure that high-quality cardio-pulmonary-resuscitation (CPR) is
      performed, many kinds of feedback devices have been developed that are helpful
      for achieving correct chest compression (CC) in manikin studies. However, the
      mattress compression depth (MCD) can cause overestimation of chest compression
      depth (CCD) during CPR using a feedback device. Herein, we propose a new method
      using a vinyl cover that encloses the foam mattress and is compressed by vacuum
      pump just before performing CPR, which could increase the performance of CCs
      during CPR. 

PMID- 24109726
TI  - Lumped parameter model of cardiovascular-respiratory interaction.
AB  - The aim of this work was to develop a lumped parameter model of the
      cardiovascular system and to couple it with a model of respiratory mechanics. In
      comparison to existing models, modifications and additions have been implemented
      to include a model of the upper limb vasculature employing the electrical analogy
      of hemodynamic variables. The model prediction of respiratory effects on arterial
      pressure was compared with in vivo invasive measurement of blood pressure in
      patients. The model indicates that the inherent coupling between the
      cardiovascular and respiratory systems can be described by mathematical
      relationships of physiological parameters with robust predictions. With
      specification of parameters based on individual measurements of cardio
      respiratory variables, the model can be used in the clinical setting of intensive
      care units to predict hemodynamic changes and to optimize ventilation and volume
      loading strategies. 

PMID- 24109727
TI  - Self biofeedback control of oxygen consumption (Vo2) during cycling exercise:
      based on its real time estimate.
AB  - The aim of this paper is to develop the self biofeedback (SBF) control of oxygen
      consumption (Vo2) during cycling exercise. The developed system uses an estimator
      that can predict Vo2 in real time by using the measurements of heart rate (HR),
      respiratory rate (RespR) and frequency of exercising activity, this terms is
      known as Exercise Rate (ER). The biofeedback command is given to the exercising
      subject in terms of the desired action required by the subject to achieve the
      targeted Vo2 (Vo2target) profile. The desired action is determined by the SBF
      system based on the current estimates of Vo2 and is communicated to the
      exercising subject by flashing an indicator on the computer screen. The results
      obtained in this study demonstrate that the estimator developed for cycling
      exercise is capable of estimating Vo2 in real time. The developed system is
      tested on six healthy male subjects. The obtained results show that the SBF
      system performs well with the average steady state error in terms of Root Mean
      Square Error (RMSE) of 1 ml/min/Kg during low intensity exercise and with RMSE of
      1.6426 ml/min/Kg during high intensity exercise. 

PMID- 24109728
TI  - Using of porous portion to simulate pulmonary resistance in the computational
      fluid dynamic models of Fontan connection.
AB  - In this study, we performed computational fluid dynamic (CFD) simulations in a
      patient-specific three-dimensional extracardiac conduit Fontan connection. The
      pulmonary resistance was incorporated in the CFD model by connecting porous
      portions in the left and right pulmonary arteries. The pressure in the common
      atrium was set as boundary conditions at the outlets of the pulmonary arteries.
      The flow rate in the innominate veins and the inferior vena cava (IVC) was set as
      inflow boundary conditions. Furthermore, the inflow rate of IVC was increased to
      2 and 3 times of that measured to perform another two simulations and the
      resistance provided by the porous portions was compared among these three
      conditions. We found out that the pulmonary resistance set as porous portion in
      the CFD models remains relatively steady despite the change of the inflow rate.
      We concluded that, in the CFD simulations for the Fontan connections, porous
      portion could be used to represent pulmonary resistance steadily. The pulmonary
      resistance and pressure in the common atrium could be acquired directly by
      clinical examination. The employment of porous portion together with pressure in
      the common atrium in the CFD model could facilitate and accurate the set of
      outlet boundary conditions especially for those actual pulmonary flow splits was
      unpredictable such as virtual operative designs related CFD simulations. 

PMID- 24109729
TI  - Feasibility study on development of Cerenkov fiber-optic dosimeter for
      radiotherapy application.
AB  - To obtain real-time dose information in photon-beam therapy using a clinical
      linear accelerator, we fabricated a novel Cerenkov fiber-optic dosimeter using
      two plastic optical fibers without employing a scintillator. In this study, the
      light intensity and spectrum of Cerenkov radiation induced by a high-energy
      photon beam were measured as functions of the irradiation angle and the length
      difference between the two plastic optical fibers in the dosimeter probe. Also,
      we obtained a percentage depth dose curve for a 6 MV photon beam with a field
      size of 10 * 10 cm(2) according to the depth of the solid water phantom. Based on
      the results of this study, it is anticipated that the proposed Cerenkov fiber
      optic dosimeter can be developed as a useful dosimeter to accurately obtain dose
      information prior to conducting radiotherapy. 

PMID- 24109730
TI  - Metallic tip enhanced fluorescence for DNA replication monitoring.
AB  - We have successfully performed localized loop-mediated isothermal reactions of
      hepatitis B virus (HBV) and hepatitis C virus (HCV) on the apex (50~100 nm) of
      metallic tips coated with Bst polymerases. The SYBR green molecules binding to
      the new formed HBV DNA inside the optical near fields were excited by two-photon
      fluorescence microscopy, and directly imaged in far field. Another reporter
      primer is used for HCV replication detection. Preliminary results are presented
      in this manuscript.

PMID- 24109731
TI  - Nanodots array rapidly fabricated by Dip-Pen nanolithography with temperature and
      humidity control.
AB  - This study demonstrates the advantage of Dip-Pen Nanolithography (DPN) as a
      research and design tool for metal nano-structure fabrications. We design two
      different gold nano-structures, which are fabricated by DPN etching method with
      temperature and humidity control. The plasmon resonance frequencies of both
      structures are measured with dark field scattering spectroscopy. Our results show
      that with temperature and humidity control, DPN is highly potential in developing
      photonic circuit, solar cell and biomedical devices due to the rapid fabrication
      and cost effectiveness. 

PMID- 24109732
TI  - Lock-in amplification for implantable multiwavelength pulse oximeters.
AB  - Standard as well as multiwavelength pulse oximetry as established methods for
      measuring blood oxygen saturation or fractions of dyshemoglobins suffer from
      different kinds of interference and noise. Employing lock-in technique as a read
      out approach for multiwavelength pulse oximetry is proposed here and strongly
      decreases such signal disturbance. An analog lock-in amplifier was designed to
      modulate multiple LEDs simultaneously and to separate the signals detected by a
      single photodiode. In vivo measurements show an improved signal-to-noise ratio of
      photoplethysmographic signals and a suppression of interference by means of the
      lock-in approach. This allows the detection of higher order overtones and,
      therefore, more detailed data for pulse wave analysis, especially for implantable
      sensors directly applied at arteries. 

PMID- 24109733
TI  - Automated temperature calculation method for DWI-thermometry: the usefulness of
      LV probability map on healthy subjects.
AB  - Diffusion-weight imaging (DWI) has already been incorporated as a regular
      sequence for patients. If DWI could indicate brain temperature without a
      complicated procedure, such information may greatly contribute to initial
      diagnosis. The temperature (T:  degrees C) was calculated using the following
      equation form the diffusion coefficient (D): T= 2256.74/ln (4.39221/D) - 273.15.
      The cerebrospinal fluid region for automated temperature computation was
      segmented by lateral ventricle probability map which was constructed from 46
      healthy volunteers. No significant differences were seen between temperatures
      using the proposed method and the manually segmented. The proposed method of
      fully automated deep brain temperature computation from DWI may prove feasible
      for application in MRI consoles. 

PMID- 24109734
TI  - Atlas-based segmentation of white matter structures from DTI using tensor
      invariants and orientation.
AB  - This paper presents a novel method for the segmentation of anatomical structures
      in the white matter from DTI (Diffusion Tensor Imaging) data. Our approach is
      based on: (a) the use of a DTI white matter atlas to guide the segmentation
      process, (b) the use of tensor invariants and the orientation information of the
      tensor as features, and (c) a statistical modeling of the data with a level set
      implementation. This formulation allows for controlling the relative importance
      of the different properties of the diffusion tensor and uses the anatomical
      information of the atlas to constrain the segmentation. The method has been
      applied to the segmentation of DTI volumes, and results show it constitutes a
      valid alternative to other approaches such as VBM or TBSS for white matter
      analysis. 

PMID- 24109735
TI  - Merging squared-magnitude approaches to DWI denoising: An adaptive Wiener filter
      tuned to the anatomical contents of the image.
AB  - We present a new method for denoising of Diffusion Weighted Images (DWI) that
      shares several desirable features of state-of-the-art proposals: 1) it works with
      the squared-magnitude signal, allowing for a closed-form formulation as a Linear
      Minimum Mean Squared Error (LMMSE) estimator, a.k.a. Wiener filter; 2) it jointly
      accounts for the DWI channels altogether, being able to unveil anatomical
      structures that remain hidden in each separated channel; 3) it uses a Non-Local
      Means (NLM)-like scheme to discriminate voxels corresponding to different fiber
      bundles, being able to enhance the anatomical structures of the DWI. We report
      extensive experiments evidencing the new approach outperforms several related
      methods for all the range of input signal-to-noise ratios (SNR). An open-source
      C++ implementation of the algorithm is also provided for the sake of
      reproducibility. 

PMID- 24109736
TI  - Cramer-Rao bound for Intravoxel Incoherent Motion Diffusion Weighted Imaging
      fitting.
AB  - The precision of parameter estimation for Intravoxel Incoherent Motion Diffusion
      Weighted Imaging (IVIM-DWI) was investigated by examining their Cramer-Rao bounds
      (CRBs) under the presence of Rician noise. Monte Carlo (MC) simulation was also
      conducted to validate the CRB results. The estimation uncertainties of true
      diffusion coefficient (D) and perfusion fraction (f0) could reach 3.89% and
      11.65% respectively with typical parameter values at a moderate signal-to-noise
      ratio (SNR) of 40. However, to estimate pseudo diffusion coefficient (D*) within
      10% uncertainty requires SNR>122. The results also showed that the estimation
      precision of each parameter is not only dependent on SNR but also their true
      values, while this mutual dependency is complicated. Under some particular cases,
      estimation uncertainty for certain parameters might be smaller than 5% at a
      moderate SNR of 40. However, the simultaneous precise estimation for all three
      parameters is theoretically difficult and highly SNR demanding. 

PMID- 24109737
TI  - Correlation between diffusion tensor tractography and proton MR spectroscopy in
      normal controls.
AB  - Tractography is a procedure that can track and demonstrate the 3D neural tracts
      of the white matter of the brain. The images of the brain are obtained by
      analyzing the diffusion tensor, identification of which can provide the
      anatomical connections of the brain. Studying these connections is integral to
      the understanding of the brain function. Specifically, the uncinate fasciculus
      and fornix, which are the white matter in the human brain, are said to be related
      to cognitive function. The tractography is calculated using diffusion tensor
      imaging (DTI) parameter. Studies have shown that the DTI parameter of dementia
      patients is lower than that of healthy individuals. It is also suggested that the
      DTI parameter of healthy individuals decreases with age. In addition, Proton MR
      Spectroscopy ((1)H-MRS) is indicative of neuronal damage and has been used for
      decades as a noninvasive technique for assessing the biochemistry of the human
      brain. This is reflected by the increasing number of clinical MRS investigations
      of neurological disorders. Thus, MRS and DTI can provide complementary images on
      white matter in brain and it is important to investigate the white matter brain
      changes by simultaneously acquiring DTI and MRS in health control subjects. In
      this research, we have calculated the correlation coefficient between the DTI
      parameter of uncinate fasciculus, fornix and (1)H-MRS. Our result shows that the
      correlation coefficient of DTI parameter and (1)H-MRS of a left fornix is 0.65 at
      the maximum. Correlation between DTI measurement and (1)H-MRS suggests the
      relationships between the uncinate fasciculus, fornix and cognitive neuronal
      function. Our finding matches previous reports on the correlation between DTI
      parameters and (1)H-MRS. 

PMID- 24109738
TI  - Estimation of fiber orientation by filtered q-ball imaging*.
AB  - We proposed a filtered q-ball imaging (fQBI) method for the reconstruction of
      fiber orientation distribution function (ODF) together with the quantitative
      comparison to unfiltered QBI. The filter kernel increases the high angular
      frequency content that is beneficial for the angular resolution in resolving
      crossing fibers. Through a series of simulations using Monte-Carlo model, the
      angular resolution of fQBI was demonstrated better than traditional QBI but the
      deviation of fiber orientation estimate also becomes larger. The improvement of
      the angular resolution can also reduce the underestimation of separation angles
      as well as the bias of fiber orientation estimations. In conclusion, fQBI was
      demonstrated to improve the angular resolution of QBI in resolving crossing
      fibers. This improvement will be helpful to precisely reconstruct fiber tract and
      brain network in applications by QBI. 

PMID- 24109739
TI  - Investigating the effects of streamline-based fiber tractography on matrix
      scaling in brain connective network.
AB  - Investigating the brain connective network using the modern graph theory has been
      widely applied in cognitive and clinical neuroscience research. In this study, we
      aimed to investigate the effects of streamline-based fiber tractography on the
      change of network properties and established a systematic framework to understand
      how an adequate network matrix scaling can be determined. The network properties,
      including degree, efficiency and betweenness centrality, show similar tendency in
      both left and right hemispheres. By employing the curve-fitting process with
      exponential law and measuring the residuals, the association between changes of
      network properties and threshold of track numbers is found and an adequate range
      of investigating the lateralization of brain network is suggested. The proposed
      approach can be further applied in clinical applications to improve the
      diagnostic sensitivity using network analysis with graph theory. 

PMID- 24109740
TI  - A prediction model for cognitive performance in health ageing using diffusion
      tensor imaging with graph theory.
AB  - In this study, we employed diffusion tensor imaging (DTI) to construct brain
      structural network and then derive the connection matrices from 96 healthy
      elderly subjects. The correlation analysis between these topological properties
      of network based on graph theory and the Cognitive Abilities Screening Instrument
      (CASI) index were processed to extract the significant network characteristics.
      These characteristics were then integrated to estimate the models by various
      machine-learning algorithms to predict user's cognitive performance. From the
      results, linear regression model and Gaussian processes model showed presented
      better abilities with lower mean absolute errors of 5.8120 and 6.25 to predict
      the cognitive performance respectively. Moreover, these extracted topological
      properties of brain structural network derived from DTI also could be regarded as
      the bio-signatures for further evaluation of brain degeneration in healthy aged
      and early diagnosis of mild cognitive impairment (MCI). 

PMID- 24109741
TI  - The accuracy and precision of signal source localization with tetrodes.
AB  - Four-sensor microelectrodes, commonly referred to as tetrodes, have the ability
      to significantly increase the signal-to-noise ratio of neuronal extracellular
      recordings. They also provide spatio-temporal information about extracellular
      action potentials (EAP) which may be used to localize and resolve individual
      neuronal signal sources. Since the relative position of sensors and neurons whose
      EAPs are recorded is not known during in vivo experiments, the accuracy and
      precision of neuronal source localization algorithms remain untested. In this
      study, electrical signals generated by a stimulator were recorded simultaneously
      with four recording micropipettes immersed in artificial cerebrospinal fluid. The
      location of the source was estimated using the multiple signal classification
      algorithm, with an accuracy and precision of ~4 um and ~7 um, respectively. These
      results suggest that in vivo localization and resolution of individual neuronal
      sources is feasible.

PMID- 24109742
TI  - Characterization of laplacian surface electromyographic signals during isometric
      contraction in biceps brachii.
AB  - Surface electromyography (sEMG) is a noninvasive technique for monitoring the
      electrical activity produced by the muscles. Usually, sEMG is performed by
      carrying out monopolar or bipolar recordings by means of conventional Ag/AgCl
      electrodes. In contrast, Laplacian recordings of sEMG could also be obtained by
      using coaxial ring electrodes. Laplacian recordings increase spatial resolution
      and attenuate other distant bioelectric interferences. Nevertheless, the spectral
      characteristics of this kind of recordings have been scarcely studied. The
      objective of this paper is to characterize the sEMG signals recorded with a
      Laplacian ring electrode and to compare them with traditional bipolar recordings
      with disc electrodes. Both kinds of signals were collected simultaneously in two
      healthy subjects during resting and sustained isometric voluntary contraction
      activities in biceps brachii. The conducted study computed the cumulative
      percentage of the power spectrum of sEMG so as to determine the energy bandwidth
      of the two kinds of recordings and the signal to noise ratio in different bands
      of the sEMG spectrum. Also, muscle fatigue, a condition when muscle force is
      reduced, was assessed using indexes from amplitude and frequency domain. The
      results of this study suggest that Laplacian sEMG has higher spectral bandwidth
      but a lower signal to noise ratio in comparison to bipolar sEMG. In addition,
      frequency fatigue indexes showed that Laplacian recording had better response
      than bipolar recording, which suggests that Laplacian electrode can be useful to
      study muscular fatigue due to better spatial resolution. 

PMID- 24109743
TI  - Impedance spectra of polypyrrole coated platinum electrodes.
AB  - Polypyrrole (PPy) coated electrodes may provide new solutions to increase the
      charge injection capacity and biocompatibility of metal electrodes in e.g.,
      neural stimulus applications. In this study, electrical impedance spectra of PPy
      coated platinum (Pt) electrodes having three different coating thicknesses were
      measured and modeled. A suitable equivalent electrical circuit providing the
      material characteristics was chosen and the impedance data was analyzed using the
      model and data fitting. The modeled parameter values of different coating
      thicknesses were compared and our results demonstrated the changes in charge
      transfer properties and mechanisms of thin and thick PPy film coatings. 

PMID- 24109744
TI  - Ear-EEG from generic earpieces: a feasibility study.
AB  - The use of brain monitoring based on EEG, in natural environments and over long
      time periods, is hindered by the limited portability of current wearable systems,
      and the invasiveness of implanted systems. To that end, we introduce an ear-EEG
      recording device based on generic earpieces which meets key patient needs
      (discreet, unobstrusive, user-friendly, robust) and that is low-cost and suitable
      for off-the-shelf use; thus promising great advantages for healthcare
      applications. Its feasibility is validated in a comprehensive comparative study
      with our established prototype, based on a personalized earpiece, for a key EEG
      paradigm. 

PMID- 24109745
TI  - Novel flexible Dry multipin electrodes for EEG: Signal quality and interfacial
      impedance of Ti and TiN coatings.
AB  - Conventional Silver/Silver-Chloride electrodes are inappropriate for routine high
      density EEG and emerging new fields of application like brain computer
      interfaces. A novel multipin electrode design is proposed. It enables rapid and
      easy application while maintaining signal quality and patient comfort. The
      electrode design is described and impedance and EEG tests are performed with
      Titanium and Titanium Nitride coated electrodes. The results are compared to
      conventional reference electrodes in a multi-volunteer study. The calculated
      signal parameters prove the multipin electrode concept to reproducibly acquire
      EEG signal quality comparable to Ag/AgCl electrodes. The promising results
      encourage further investigation and can provide a technological base for future
      preparation-free multichannel EEG systems. 

PMID- 24109746
TI  - Comb-shaped polymer-based Dry electrodes for EEG/ECG measurements with high user
      comfort.
AB  - Soft, comfortable polymer-based dry electrodes are fabricated. Impedance and
      biopotential measurements are carried out to compare the performance of
      conventional gel electrodes with our dry electrodes. The impedance of our dry
      electrodes is reduced by adding more conductive additives to the polymer
      material. To further lower the impedance, two skin pretreatment techniques are
      evaluated regarding their influence on skin impedance. However, these techniques
      are found to have only temporary beneficial effects. Finally biopotential
      measurements (both ECG and EEG) are performed using our soft polymer electrodes.
      The ECG signal acquired with both gel and our polymer electrodes demonstrates
      high degree of similarity. Therefore, heart beat detection is straightforward. To
      enable monitoring of EEG signals with smaller amplitudes, our dry electrodes need
      to be combined with pre-amplifiers. Initial EEG tests show that the alpha waves
      are clearly identifiable with the dry electrodes when subjects close their eyes.
      Based on the results, combining with sophisticated signal acquisition
      electronics, the dry electrodes provide a high user comfort solution for high
      quality biopotential measurements, even on very hairy skin. 

PMID- 24109747
TI  - Multi-layered fabric electrode for movement artifact reduction in capacitive ECG
      measurement.
AB  - An electrode configuration composed of multi-layered fabric electrodes were
      examined and compared with that composed of non-layered fabric electrodes in
      terms of movement artifact reduction when using the electrodes in capacitive
      electrocardiogram measurement from human buttocks in a vibrating environment.
      Experiments performed with six participants revealed that the multi-layered
      configuration composed of sensing electrode, driven shield and ground layers
      reduced amplitude of movement artifact significantly than the non-layered
      configuration. 

PMID- 24109748
TI  - Portable bioimpedance monitor evaluation for continuous impedance measurements.
      Towards wearable plethysmography applications.
AB  - Personalised Health Systems (PHS) that could benefit the life quality of the
      patients as well as decreasing the health care costs for society among other
      factors are arisen. The purpose of this paper is to study the capabilities of the
      System-on-Chip Impedance Network Analyser AD5933 performing high speed single
      frequency continuous bioimpedance measurements. From a theoretical analysis, the
      minimum continuous impedance estimation time was determined, and the AD5933 with
      a custom 4-Electrode Analog Front-End (AFE) was used to experimentally determine
      the maximum continuous impedance estimation frequency as well as the system
      impedance estimation error when measuring a 2R1C electrical circuit model.
      Transthoracic Electrical Bioimpedance (TEB) measurements in a healthy subject
      were obtained using 3M gel electrodes in a tetrapolar lateral spot electrode
      configuration. The obtained TEB raw signal was filtered in MATLAB to obtain the
      respiration and cardiogenic signals, and from the cardiogenic signal the
      impedance derivative signal (dZ/dt) was also calculated. The results have shown
      that the maximum continuous impedance estimation rate was approximately 550
      measurements per second with a magnitude estimation error below 1% on 2R1C
      parallel bridge measurements. The displayed respiration and cardiac signals
      exhibited good performance, and they could be used to obtain valuable information
      in some plethysmography monitoring applications. The obtained results suggest
      that the AD5933-based monitor could be used for the implementation of a portable
      and wearable Bioimpedance plethysmograph that could be used in applications such
      as Impedance Cardiography. These results combined with the research done in
      functional garments and textile electrodes might enable the implementation of PHS
      applications in a relatively short time from now. 

PMID- 24109749
TI  - Using transmission properties to determine blood glucose levels.
AB  - A non-intrusive technique based on modeling the body as a transmission channel
      was tested in vitro and was shown to perform equally with a commercial OTS
      glucose meter on saline-glucose solutions of concentrations of glucose from 30 to
      300 mg/dL. The technique uses an initial frequency sweep to locate a frequency
      where a resonant response occurs. At that position the phase is changing rapidly
      and can therefore be used more easily to measure a phase difference. This sweet
      spot can be natural or assisted. Present efforts are toward a system which uses a
      feedback amplifier with a low phase margin in order to easily find the the region
      of rapid phase change. Initial tests measuring known glucose concentrations with
      an OTS glucose meter and then using the proposed technique were shown to
      correlate with the actual concentrations with an R(2) = 0.9879 and R(2) = 0.9952
      respectively (with one outlier data point removed). Further tests are being
      conducted in vitro on whether other interfering agents may disrupt results. The
      ultimate goal of the development of this technique is to fabricate a device that
      is worn externally on the upper arm and does not require blood for testing. A
      device is being built and is scheduled for human subject testing in Summer 2013.
      Some results of human testing may be available at the EMBC conference. Human
      testing will involve measurements done with our device against an OTS glucose
      meter and results compared. The future goal is to refine the device so that it
      can be worn 24 hours a day and will automatically test the wearer at a user
      specified interval such as 10 or 20 minutes by transmitting a low power signal
      for a few microseconds. Power levels are still being determined but, in
      simulation, nano-watts was sufficient for the distance needed to travel which is
      orders of magnitude less than present day cell phones. To evaluate safety of the
      system, 3D electromagnetic simulations are being carried out with the device
      positioned strapped to the upper arm. Simulations show transmission along the
      targeted paths which suggests that affective glucose sensing is possible with
      this device. 

PMID- 24109750
TI  - Smart textile device using ion polymer metal compound.
AB  - We have developed a smart textile device that detects angular displacement of
      attached surface using ion polymer metal compound. The device was composed of ion
      polymer metal compound (IPMC) which was fabricated from Nafion resin by heat
      press and chemical gold plating. The generated voltage from IPMC was measured as
      a function of bending angle. Fabricated IPMC device was weaved into a cotton
      cloth and multidirectional movements were detected. 

PMID- 24109751
TI  - A new virtual instrument for estimating punch velocity in combat sports.
AB  - For improving the performance in combat sport, especially percussion, it is
      necessary achieving high velocity in punches and kicks. The aim of this study was
      to evaluate the applicability of 3D accelerometry in a Virtual Instrumentation
      System (VIS) designed for estimating punch velocity in combat sports. It was
      conducted in two phases: (1) integration of the 3D accelerometer with the
      communication interface and software for processing and visualization, and (2)
      applicability of the system. Fifteen karate athletes performed five gyaku zuki
      type punches (with reverse leg) using the accelerometer on the 3rd metacarpal on
      the back of the hand. It was performed nonparametric Mann-Whitney U-test to
      determine differences in the mean linear velocity among three punches performed
      sequentially (p <0.05). The maximum velocities measured varied in the range of 10
      and 10.2 m/s and the mean velocities from 6 to 6.8 m/s. There was no difference
      on the mean velocity for the tested punches. The VIS demonstrated regularity and
      proper functionality for assessing punches in combat sport. 

PMID- 24109752
TI  - Identification of altered MET network in oral cancer progression based on
      nonparametric network design.
AB  - Oral cancer is characterized by multiple genetic events such as alterations of a
      number of oncogenes and tumour suppressor genes. The aim of this study is to
      identify genes and their functional interactions that may play a crucial role on
      a specific disease-state, especially during oral cancer progression. We examine
      gene interaction networks on blood genomic data, obtained from twenty three oral
      cancer patients at four different time stages. We generate the gene-gene networks
      from sparse experimental temporal data using two methods, Partial Correlations
      and Kernel Density Estimation, in order to capture genetic interactions. The
      network study reveals an altered MET (hepatocyte growth factor receptor) network
      during oral cancer progression, which is further analyzed in relation to other
      studies. 

PMID- 24109754
TI  - Hierarchical clustering combining numerical and biological similarities for gene
      expression data classification.
AB  - High throughput data analysis is a challenging problem due to the vast amount of
      available data. A major concern is to develop algorithms that provide accurate
      numerical predictions and biologically relevant results. A wide variety of tools
      exist in the literature using biological knowledge to evaluate analysis results.
      Only recently, some works have included biological knowledge inside the analysis
      process improving the prediction results. 

PMID- 24109755
TI  - Nucleotide sequence alignment using sparse coding and belief propagation.
AB  - Advances in DNA information extraction techniques have led to huge sequenced
      genomes from organisms spanning the tree of life. This increasing amount of
      genomic information requires tools for comparison of the nucleotide sequences. In
      this paper, we propose a novel nucleotide sequence alignment method based on
      sparse coding and belief propagation to compare the similarity of the nucleotide
      sequences. We used the neighbors of each nucleotide as features, and then we
      employed sparse coding to find a set of candidate nucleotides. To select optimum
      matches, belief propagation was subsequently applied to these candidate
      nucleotides. Experimental results show that the proposed approach is able to
      robustly align nucleotide sequences and is competitive to SOAPaligner [1] and BWA
      [2]. 

PMID- 24109756
TI  - Optimisation algorithms for microarray biclustering.
AB  - In providing simultaneous information on expression profiles for thousands of
      genes, microarray technologies have, in recent years, been largely used to
      investigate mechanisms of gene expression. Clustering and classification of such
      data can, indeed, highlight patterns and provide insight on biological processes.
      A common approach is to consider genes and samples of microarray datasets as
      nodes in a bipartite graphs, where edges are weighted e.g. based on the
      expression levels. In this paper, using a previously-evaluated weighting scheme,
      we focus on search algorithms and evaluate, in the context of biclustering,
      several variations of Genetic Algorithms. We also introduce a new heuristic
      "Propagate", which consists in recursively evaluating neighbour solutions with
      one more or one less active conditions. The results obtained on three well-known
      datasets show that, for a given weighting scheme, optimal or near-optimal
      solutions can be identified. 

PMID- 24109757
TI  - Role for gene sequence, codon bias and mRNA folding energy in modulating
      structural symmetry of proteins.
AB  - Structural symmetry in proteins is commonly observed in the majority of
      fundamental protein folds. Meanwhile, nascent polypeptide chains of proteins have
      the potential to start the co-translational folding process and this process can
      have drastic effects on protein structure. Thus we are interested in
      understanding mechanisms that gene adopts in specifying structural symmetry in
      proteins. In the present paper, we reveal that for two representative symmetric
      proteins from (abeta)8-barrel fold and beta-trefoil fold, intragenic symmetry is
      detected in the corresponding gene sequences. Codon bias and mRNA folding energy
      might be involved in mediating translation speed for the formation of structural
      symmetry: at least one major decrease in both codon bias and mRNA folding energy
      can be observed in the connecting region of the symmetric substructures along the
      codon sequence. Results suggest that gene duplication and fusion is responsible
      for structural symmetry in these proteins, and the usage of rare codons or higher
      order of secondary structure near the boundaries of symmetric substructures might
      be selected in order to slow down translation speed for effectively co
      translational folding process of symmetric proteins. 

PMID- 24109758
TI  - Systemes analysis of interactions between microRNAs and genes in hepatocellular
      carcinoma.
AB  - MicroRNAs (miRNAs) are short noncoding RNAs and can regulate gene expression at
      the transcriptional and/or translational levels. There is mounting evidence that
      miRNAs play an important role in the control of the dynamics of localized gene
      expression. Expression profiling of miRNA in various cancers revealed that miRNA
      profiles could discriminate malignancies from their counter parts. In this study,
      to investigate the localized effect of miRNA in cancer, we analyzed gene and
      miRNA expressions in hepatocellular carcinoma (HCC) and surrounding nontumor
      tissues. Based on gene expression levels around miRNAs, we investigated how many
      miRNAs correlated positively/negatively in expression with genes in the vicinity.
      Next, the Pearson correlation coefficients were compared between the HCC and
      nontumor tissues. The results imply that the relationship between the intronic
      miRNAs and their host genes was altered in HCC, and that feedback loops including
      the host gene, intronic miRNA, target genes might be formed in HCC. 

PMID- 24109759
TI  - Dictionary learning improves subtyping of breast cancer aCGH data.
AB  - The advent of Comparative Genomic Hybridization (CGH) data led to the development
      of new mathematical models and computational methods to automatically infer
      chromosomal alterations. In this work we tackle a standard clustering problem
      exploiting the good representation properties of a novel method based on
      dictionary learning. The identified dictionary atoms, which show co-occuring
      shared alterations among samples, can be easily interpreted by domain experts. We
      compare a state-of-the-art approach with an original method on a breast cancer
      dataset. 

PMID- 24109760
TI  - Combination of gene expression and genome copy number alteration has a prognostic
      value for breast cancer.
AB  - Specific genome copy number alterations, such as deletions and amplifications are
      an important factor in tumor development and progression, and are also associated
      with changes in gene expression. By combining analyses of gene expression and
      genome copy number we identified genes as candidate biomarkers of BC which were
      validated as prognostic factors of the disease progression. These results suggest
      that the proposed combined approach may become a valuable method for BC
      prognosis. 

PMID- 24109761
TI  - Measurement of swallowing using flexible polymer sensor.
AB  - We proposed a new method to measure swallowing in this study. A flexible polymer
      sensor was used to measure human swallowing. Electromyogram (EMG) of suprahyoid
      muscles were measured as a reference of swallowing. We also developed a
      measurement system for the flexible polymer sensor, which consists of two
      measurement circuits; the 1(st) one measures the voltage of flexible polymer
      sensor, and the 2(nd) one EMG of suprahyoid muscles. We conducted measurement
      experiments focused on human swallowing to confirm the ability of this sensor. At
      the experiment one subject was asked to sit in three different postures and to
      drink a cup of water. Results show that human swallowing can be detected by this
      flexible polymer sensor. 

PMID- 24109762
TI  - Measurement of tongue-artificial nipple contact force in infants with sucking
      difficulties.
AB  - Infants are known to suckle and ingest breast milk by wrapping the tongue around
      a nipple, writhing the tongue, and pressing the nipple. However, the dynamic
      mechanisms of tongue movement are still obscure, and factors related to sucking
      difficulties of infants are not well understood. We developed an artificial
      nipple installed with small cantilever-type sensors and directly measured the
      force applied on the nipple by the tongue. Small force sensors were arranged
      within the artificial nipple in a two-dimensional matrix of 3 * 2 to measure the
      force at 6 points. Subjects were 20 healthy infants (Group A) and 5 infants who
      had difficulty sucking (Group B). The latter could not breastfeed well and were
      fed from bottles or tubes. Informed consent was provided by the parents or
      guardians. The measured maximum force at the tip of the nipple was 1.4 +/- 0.4 N
      and 1.2 +/- 0.3 N (mean +/- SD) in Groups A and B, respectively. At the base of
      the nipple, the maximum force recorded was 0.8 +/- 0.5 N and 0.3 +/- 0.3 N (mean
      +/- SD), respectively, showing a statistically significant difference (p<0.05).
      The sucking period was 0.6 +/- 0.1 s (mean +/- SD) in both groups. The difference
      in time necessary to reach the maximum forces between the sensors at the tip and
      base was 39.7 +/- 28.8 ms (mean +/- SD) and 37.2 +/- 75.9 ms in Groups A and B,
      respectively.

PMID- 24109763
TI  - Intracranial temperature and pressure measurement: in vitro temperature sensing
      characteristics of the dual sensing element.
AB  - A pressure sensor has been used to measure temperature concurrently. We have
      designed, and characterized the measurement of temperature from the same sensor
      to allow simultaneous monitoring of intracranial temperature and pressure. The
      temperature measurement has a sensitivity of 85.08 mV/ degrees C across the
      measurement range 20-45  degrees C. The time constant of the temperature sensor
      is 150 ms. We have evaluated the accuracy of the temperature measurement and the
      long term drift of 13 sensors over 28 days. The mean difference of the
      temperature measurements from the reference measurements was less than 0.2 
      degrees C. 

PMID- 24109764
TI  - Developing a thermoacoustic sensor adaptive to ambient temperatures.
AB  - In this paper, a simple and adaptive thermoacoustic sensor was designed to
      measure Low Intensity Pulsed Ultrasound (LIPUS). Compared to other thermoacoustic
      sensor designs, our novelty lies in (i) integrating an ultrasound medium layer
      during the measurement to simplify the complicated set-up procedures and (ii)
      taking the effect of ambient temperatures into design consideration. After
      measuring temperature increases with various ambient temperatures under different
      ultrasound intensities, a relationship among ultrasound intensities, ambient
      temperatures and coefficients of temporal temperature changes was calculated. Our
      improved design has made the sensor easy to operate and its performance more
      accurate and consistent than the thermoacoustic sensor designs without
      considering ambient temperatures. In all, our improved design greatly enhances
      the thermoacoustic sensor in practical ultrasound calibration. 

PMID- 24109765
TI  - Smart sensing of tool/tissue interaction by resistive coupling.
AB  - A smart sensing of tool-tissue interaction is required to monitor the surgical
      task without disturbing the tool manipulation. We proposed a new tactile sensing
      method that enables us to detect the tool-tissue interaction with a simple
      hardware by resistive coupling. The system consists of two electrodes, a bridge
      circuit and a differential amplifier for the robust sensing of the contact
      resistance between the tool and tissue. In order to evaluate the sensing method,
      we investigated the relationship between the sensor output and the deformation of
      a wet sponge sample by retraction task. According to the model fitting of the
      deformation-output profile, we concluded that the proposed sensor provide enough
      reproducibility in the simple situation. Furthermore, we confirmed that the
      developed sensor works with a biological sample. 

PMID- 24109766
TI  - Improving the function of dopamine electrodes with novel carbon materials.
AB  - For therapeutic purposes, an accurate measurement of dopamine level in situ would
      be highly desirable. A novel strategy for the selective determination of dopamine
      concentration based on the diamond-like carbon (DLC) electrode is presented in
      this abstract. The developed DLC electrode is able to detect 10 uM dopamine and
      has improved sensitivity compared to platinum. Compared to carbon fiber
      electrodes, the DLC electrode is more stable because the background current is
      much lower. 

PMID- 24109767
TI  - In-depth analysis of interrelation between quality scores and real errors in
      Illumina reads.
AB  - In sequencing results, the quality score is reported for each base, representing
      the probability that the base is called incorrectly. The notion of quality scores
      was initially developed for conventional Sanger sequencing, but is widely used
      for next-generation sequencing techniques, including Illumina. In this paper, we
      carry out in-depth analysis of quality scores reported for Illumina reads and
      present how they are related to real errors in the reads. We confirmed strong
      interrelation between quality scores and real errors in Illumina reads, and
      observed that reverse reads tend to have lower quality scores than forward reads
      in paired-end reads do. In addition, we discovered other interesting patterns
      from quality score analysis. Our hope is that the findings in this paper will be
      helpful for designing error-correction and/or filtering methods for next
      generation sequencing. 

PMID- 24109768
TI  - Efficient Markov clustering algorithm for protein sequence grouping.
AB  - In this paper we propose an efficient reformulation of a Markov clustering
      algorithm, suitable for fast and accurate grouping of protein sequences, based on
      pairwise similarity information. The proposed modification consists of optimal
      reordering of rows and columns in the similarity matrix after every iteration,
      transforming it into a matrix with several compact blocks along the diagonal, and
      zero similarities outside the blocks. These blocks are treated separately in
      later iterations, thus reducing the computational burden of the algorithm. The
      proposed algorithm was tested on protein sequence databases like SCOP95. In terms
      of efficiency, the proposed solution achieves a speed-up factor in the range 15
      50 compared to the conventional Markov clustering, depending on input data size
      and parameter settings. This improvement in computation time is reached without
      losing anything from the partition accuracy. The convergence is usually reached
      in 40-50 iterations. Combining the proposed method with sparse matrix
      representation and parallel execution will certainly lead to a significantly more
      efficient solution in future. 

PMID- 24109769
TI  - Contact potentials via wavelet transform for prediction of subcellular
      localizations in gram negative bacterial proteins.
AB  - Predicting the localization of a protein has become a useful practice for
      inferring its function. Most of the reported methods to predict subcellular
      localizations in Gram-negative bacterial proteins have shown a low false positive
      rate. However, some subcellular compartmens like "periplasm" and "extracellular
      medium" are difficult to predict and remain high false negative rates. In this
      paper, a method based on representation from statistical contact potentials and
      wavelet transform is presented. The wavelet-based method achieves an overall high
      performance holding low false and negative rates particularly on periplasm and
      extracellular medium. Results suggest the contact potentials as an useful
      alternative to characterize protein sequences. 

PMID- 24109770
TI  - Benchmarking RNA-Seq quantification tools.
AB  - RNA-Seq, a deep sequencing technique, promises to be a potential successor to
      microarrays for studying the transcriptome. One of many aspects of
      transcriptomics that are of interest to researchers is gene expression
      estimation. With rapid development in RNA-Seq, there are numerous tools available
      to estimate gene expression, each producing different results. However, we do not
      know which of these tools produces the most accurate gene expression estimates.
      In this study we have addressed this issue using Cufflinks, IsoEM, HTSeq, and
      RSEM to quantify RNA-Seq expression profiles. Comparing results of these
      quantification tools, we observe that RNA-Seq relative expression estimates
      correlate with RT-qPCR measurements in the range of 0.85 to 0.89, with HTSeq
      exhibiting the highest correlation. But, in terms of root-mean-square deviation
      of RNA-Seq relative expression estimates from RT-qPCR measurements, we find HTSeq
      to produce the greatest deviation. Therefore, we conclude that, though Cufflinks,
      RSEM, and IsoEM might not correlate as well as HTSeq with RT-qPCR measurements,
      they may produce expression values with higher accuracy.

PMID- 24109771
TI  - Implementation of a custom hardware-accelerator for short-read mapping using
      Burrows-Wheeler alignment.
AB  - The mapping of millions of short DNA fragments to a large genome is a great
      challenge in modern computational biology. Usually, it takes many hours or days
      to map a large genome using software. However, the recent progress of
      programmable hardware such as field programmable gate arrays (FPGAs) provides a
      cost effective solution to this challenge. FPGAs contain millions of programmable
      logic gates to design massively parallel accelerators. This paper proposes a
      hardware architecture to accelerate the short-read mapping using Burrows-Wheeler
      alignment. The speed-up of the proposed architecture is estimated to be at least
      10 times compared to its equivalent software application. 

PMID- 24109772
TI  - EpiDiff: entropy-based quantitative identification of differential epigenetic
      modification regions from epigenomes.
AB  - Genome-wide epigenetic modification dynamics, including DNA methylation and
      chromatin modification, are involved in biological processes such as development,
      aging, and disease. Quantitative identification of differential epigenetic
      modification regions (DEMRs) from various temporal and spatial epigenomes is a
      crucial step towards investigating the relationship between epigenotype and
      phenotype. Here, we describe EpiDiff (http://bioinfo.hrbmu.edu.cn/epidiff/), an
      integrated software platform that supports quantification of epigenetic
      difference and identification of DEMRs by Shannon entropy. Two main modules,
      quantitative differential chromatin modification region (QDCMR) and quantitative
      differentially methylated region (QDMR) are provided for bioinformatic analysis
      of chromatin modifications and DNA methylation data, respectively. The third
      module, quantitative differential expressed gene (QDEG), can be used to identify
      differentially expressed genes. The platform-free and species-free nature of
      EpiDiff makes it potentially applicable to a wide variety of epigenomes at an
      unprecedented scale and resolution. The graphical user interface provides
      biologists with a practicable and reliable way to analyze and visualize
      epigenetic difference. 

PMID- 24109773
TI  - Genetic algorithm optimization of transcutaneous energy transmission systems for
      implantable ventricular assist devices.
AB  - Transcutaneous energy transmission systems (TETS) wirelessly transmit power
      through the skin. TETS is particularly desirable for ventricular assist devices
      (VAD), which currently require cables through the skin to power the implanted
      pump. Optimizing the inductive link of the TET system is a multi-parameter
      problem. Most current techniques to optimize the design simplify the problem by
      combining parameters leading to sub-optimal solutions. In this paper we present
      an optimization method using a genetic algorithm to handle a larger set of
      parameters, which leads to a more optimal design. Using this approach, we were
      able to increase efficiency while also reducing power variability in a prototype,
      compared to a traditional manual design method. 

PMID- 24109774
TI  - A magnetic fluid seal for rotary blood pumps: image and computational analyses of
      behaviors of magnetic fluids.
AB  - A magnetic fluid (MF) seal has excellent durability. The performance of an MF
      seal, however, has been reported to decrease in liquids (several days). We have
      developed an MF seal that has a shield mechanism. The seal was perfect for 275
      days in water. To investigate the effect of a shield, behaviors of MFs in a seal
      in water were studied both experimentally and computationally. (a) Two kinds of
      MF seals, one with a shield and one without a shield, were installed in a
      centrifugal pump. Behaviors of MFs in the seals in water were observed with a
      video camera and high-speed microscope. In the seal without a shield, the surface
      of the water in the seal waved and the turbulent flow affected behaviors of the
      MFs. In contrast, MFs rotated stably in the seal with a shield in water even at
      high rotational speeds. (b) Computational fluid dynamics analysis revealed that a
      stationary secondary flow pattern in the seal and small velocity difference
      between magnetic fluid and water at the interface. These MF behaviors prolonged
      the life of an MF seal in water. 

PMID- 24109775
TI  - Evaluation of titanium mesh electrode using for transcutaneous intrabody
      communication by tissue-electrode impedance.
AB  - We developed a new transcutaneous communication system (TCS) that uses the human
      body as a conductive medium for monitoring and controlling an artificial heart
      and other implanted artificial organs in the body. The TCS is able to transmit
      data between everywhere on the surface of the body and everywhere inside the
      body, however poor contact between tissue and the electrode influences on
      communication performance. Thus in this study, we have developed a titanium mesh
      electrode for the internal transmission electrode. The titanium mesh electrode
      has advantages of histocompatibility and mechanical stable contact to the tissue
      by infiltration of the tissue into the titanium mesh like as an extracellular
      matrix. There titanium mesh electrodes were implanted separately into the dorsal
      region of the rats under the skin and the electrical performance of the titanium
      mesh electrode was evaluated by means of measuring the electrode-tissue boundary
      resistance. In vivo experimental results showed that the titanium mesh electrode
      had stable mechanical contact to tissue and lower electrode -tissue boundary
      resistance. In conclusion, the titanium mesh electrode showed excellent
      histocompatibility it realized stable contact to tissue as anchor, and it had
      superior electrical property. Thus the titanium mesh electrode is suitable for an
      internal electrode of the TCS to monitor artificial organs implanted into the
      body. 

PMID- 24109776
TI  - Relation between left atrial pressure and the corresponding pulse pressure in the
      helical flow total artificial heart.
AB  - The present control method used in our helical flow total artificial heart
      (HFTAH) would only need four parameters. Nowadays, gauge pressure sensors are
      being used to obtain the pressure needed for control parameters. Nevertheless,
      there are also many following problems such as calibration, maintenance, offset
      drift and infection due to the skin-penetrative lines for the usage of gauge
      pressure sensor. Therefore, it is preferable to find another substitutional way
      instead of the gauge sensor to measure the pressure. In addition, with an eye to
      completing an implantable HFTAH, we would like to do without any lines through
      the experiment animal. Therefore, it was confirmed in this study that whether
      there is a relation between the left atrial pressure (LAP) and its pulse pressure
      (amplitude). Subsequently the mean value of LAP and its amplitude were
      quantified. There are two methods used in this study to process the data. Method
      one, frequency spectrum analysis, is to quantify the signals by getting the
      absolute value of amplitude for a fixed heartbeat analysis. Method two, by using
      the synchronous detection method, it is postulated to be more applicable to
      variant heartbeat data with 1/R control. By the relation of LAP and the pulse
      pressure acquired in the above two methods, as long as the amplitude of LAP is
      known by the absolute pressure sensor, it's able to obtain the mean value of LAP
      (for it suggests a linear relation). Therefore the characteristic could
      substitute one of the control parameter (that is the LAP), and the other three
      parameters will be acquired by estimation thus it doesn't need to measure them
      additionally. Consequently, it is expected that acquiring LAP by absolute
      pressure sensor for one of the control parameters could attain to an implantable
      HFTAH. 

PMID- 24109777
TI  - Physiological control of implantable rotary blood pumps for heart failure
      patients.
AB  - In general, patient variability and diverse environmental operation makes
      physiological control of a left ventricular assist device (LVAD) a complex and
      complicated problem. In this work, we implement a Starling-like controller which
      adjusts mean pump flow using pump flow pulsatility as the feedback parameter. The
      linear relationship between mean pump flow and pump flow pulsatility forms the
      desired flow of the Starling-like controller. A tracking control algorithm based
      on sliding mode control (SMC) has been implemented. The controller regulates the
      estimated mean pulsatile flow (Qp) and flow pulsatility (PIQp) generated from a
      model of the assist device. A lumped parameter model of the cardiovascular system
      (CVS) was used to test the control strategy. The immediate response of the
      controller was evaluated by inducing a fall in left ventricle (LV) preload
      following a reduction in circulating blood volume. The simulation supports the
      speed and robustness of the proposed strategy.

PMID- 24109778
TI  - Modeling aortic valve closure under the action of a ventricular assist device.
AB  - The support of a failing heart with pump devices has been an essential element in
      cardiac health care for several decades. It is therefore important to understand
      the left ventricular response to the pumping action of these devices when
      connected to the native heart. Furthermore, monitoring of aortic valve opening
      and closure is important in avoiding valve stenosis and thrombogenesis during
      pump support. This paper reports the first steps in simulating the effects of
      outlet pump pressure on aortic valve closure of the heart assisted by an
      implantable blood pump. A two-dimensional fluid structure interaction aortic
      valve model is presented with blood flow in left ventricular chamber using the
      Arbitrary Lagrangian-Eulerian Finite Element Method formulation to predict the AV
      closure during outflow of blood from the left ventricle into the left ventricular
      assist device (LVAD). 

PMID- 24109779
TI  - Peristaltic hemodynamics of a new pediatric circulatory assist system for Fontan
      circulation using shape memory alloy fibers.
AB  - Fontan procedure is one of the common surgical treatments of congenital heart
      diseases. Patients with Fontan circulation have single ventricle in the systemic
      circulation with the total cavopulmonary connection. We have been developing a
      pulmonary circulatory assist device using shape memory alloy fibers for Fontan
      circulation with total cavopulmonary connection. It consisted of the shape memory
      alloy fibers, the diameter of which are 100 um. The fibers could wrap the ePTFE
      conduit for Fontan TCPC connection from the outside. We designed the sequential
      motion control system for sophisticated pulmonary hemodynamics by the pulsatile
      flow generation. In order to achieve pulsatile flow assistance in pulmonary
      arterial system, we fabricated a mechanical structure by sequential contraction
      of shape memory alloy fibers. Then, we developed a sequential contraction
      controller for the assist system, which could reproduce the wall contractile
      velocity at 6.0 to 20.0 cm/sec. We examined hemodynamic characteristic of its
      function using a mock circulatory system, which consisted of two overflow tanks
      representing venous and pulmonary arterial pressures in Fontan circulation. As a
      result, the pulmonary circulation assist device with sequential contraction could
      achieve effective promotion of the pulsatility in pulmonary arterial flow. 

PMID- 24109780
TI  - Noninvasive assessment of left ventricular force-frequency relationships by
      measuring carotid arterial wave intensity during exercise stress.
AB  - BACKGROUND: Evaluation of the contractile state of the left ventricle during
      exercise is important in drawing up a protocol of cardiac rehabilitation. It has
      been demonstrated that color Doppler- and echo tracking-derived carotid arterial
      wave intensity is a sensitive index of global left ventricular (LV)
      contractility. OBJECTIVES: We assessed the feasibility of measuring carotid
      arterial wave intensity and determining force-frequency (contractility-heart
      rate) relationships (FFR's) during exercise totally noninvasively. METHODS: We
      measured carotid arterial wave intensity with a combined color Doppler and echo
      tracking system in 15 healthy young male volunteers (age 20.8 +/- 1.3 years) at
      rest and during exercise. FFR's were constructed by plotting the maximum value of
      wave intensity (WD1) against heart rate (HR). RESULTS: WD1 increased linearly
      with an increase in HR. The goodness-of-fit of the regression line of WD1 on HR
      in each subject was very high (r2 0.67 ~ 0.91, p < 0.0001 respectively). The
      slope of the WD1-HR relation ranged from 0.31 to 1.52 [m/s(3)(beat/min)].
      CONCLUSIONS: A global LV FFR can be generated in healthy young volunteers with an
      entirely noninvasive combination of exercise and wave intensity. These data
      should show the potential usefulness of FFR in the context of cardiac
      rehabilitation.

PMID- 24109781
TI  - Effective arterial elastance and arterial compliance in heart failure patients
      with preserved ejection fraction.
AB  - Heart failure (HF) patients have often been observed to have their ejection
      fractions somewhat preserved (HFpEF). Since left ventricular (LV) ejection is
      dependent on the coupled arterial load, the preserved ejection may be dependent
      on the effective arterial elastance (Ea). Whether this is indeed the case is
      subject to further analysis. We investigated this aspect in 67 patients with
      cardiac disease; 34 of them met the matching criteria for HFpEF. Both Ea, an
      arterial system (ASy) property, and aortic compliance (C), a physical property,
      were obtained in an attempt to differentiate the LV-ASy interaction in HFpEF and
      HFrEF (reduced ejection fraction) patients. Outcome of the study allowed us to
      conclude that Ea does not parallel changes in C. While Ea may be useful in
      assessing the severity of HFrEF, it is a weak indicator of EF dependence in HFpEF
      patients. 

PMID- 24109782
TI  - Myocardial performance index is sensitive to changes in cardiac contractility,
      but is also affected by vascular load condition.
AB  - Myocardial performance index (MPI), or Tei index, is measured by Doppler
      echocardiography in clinical practice. MPI has been shown to be useful in
      evaluating left ventricular (LV) performance and predicting prognosis in cardiac
      patients. However, the effects of LV load and contractile states on MPI remain to
      be thoroughly investigated. In 14 anesthetized dogs, we obtained LV pressure
      volume relationship with use of sonomicrometry and catheter-tip manometry. MPI
      was determined from the time derivative of LV volume and pressure. LV end
      systolic pressure-volume ratio (Ees'), effective arterial elastance (Ea) and LV
      end-diastolic volume (Ved) were used as indices of LV contractility, afterload
      and preload, respectively. Hemodynamic conditions were varied over wide ranges
      [heart rate (HR), 66-192 bpm; mean arterial pressure, 71-177 mmHg] by infusing
      cardiovascular agents, by inducing ischemic heart failure and by electrical
      atrial pacing. Multiple linear regression analysis of pooled data (66 data sets)
      indicated that MPI (0.6-1.8) significantly correlated with Ees' [1.5-17.5 mmHg .
      ml(-1), p<0.0001, standard partial regression coefficient (beta) =-0.66], Ea (3.6
      21.9 mmHg . ml(-1), p<0.001, beta = 0.4) and Ved (11-100 ml, p<0.0001, beta = 
      0.69). MPI directly correlated with the time constant of isovolumic relaxation
      (19-66 ms, p<0.05), but not with HR or LV diastolic-stiffness (all p>0.1).
      Theoretical analysis also indicated that MPI decreases following the increases in
      LV contractility and in preload, while it increases in response to an increase in
      LV afterload. We conclude that MPI sensitively detects changes in LV
      contractility. However, MPI is also affected by changes in LV afterload and
      preload.

PMID- 24109783
TI  - DT-MRI measurement of myolaminar structure: accuracy and sensitivity to time post
      fixation, b-value and number of directions.
AB  - DT-MRI has been widely used to quantify myocardial fiber and laminar
      orientations. These structural orientations influence both the spread of
      excitation and the reorganization of the myocardium during contraction and are
      altered in disease states. Studies have sought to validate DT-MRI but questions
      remain about the accuracy of the method and its sensitivity to the time post
      fixation and imaging parameters, including b-value, number of diffusion
      directions and image voxel size. The advent of high-spatial resolution ex vivo
      MRI and structure tensor (ST) analysis provides a means of direct validation of
      DT-MRI and assessment of sensitivity to the b-value, the number of diffusion
      directions and the image voxel size. We find that, with the fixation method we
      used, structure does not change with time (up to 72 hours). We show that DT-MRI
      and ST/HR-MRI are markedly similar measures of fiber orientation but DT-MRI and
      ST are much less similar measures of laminar orientation. DT-MRI performance is
      not sensitive to the number of directions, with similar structural orientations
      measured with 6 or 12 directions. Likewise, DT-MRI performance is generally
      insensitive to b-value, but laminar measurement is moderately more accurate at b
      = 500 than for higher b-values. 

PMID- 24109784
TI  - FSI simulation of intra-ventricular flow in patient-specific ventricular model
      with both mitral and aortic valves.
AB  - Investigating the intra-ventricular flow is the most important to understand the
      left ventricular function. In this study, we proposed a fluid-structure
      interaction (FSI) approach to simulate the blood flow in patient-specific model
      by combining both mitral and aortic valves. To accommodate the large mesh
      deformation, moving arbitrary Lagrangian-Eulerian (ALE) meshes were used for
      moving ventricular wall and rotating leaflets of valves. The left ventricular
      wall was predescribed according to the points acquired from magnetic resonance
      image (MRI). Mitral and aortic valves were integrated into the model by assuming
      each leaflet as a rigid body. Fluid-structure interaction (FSI) approach was
      adopted to capture the rapid motion of leaflets. The simulation results were
      qualitatively similar to the measurements reported in literatures. To the best of
      our knowledge, this is the first to simulate the patient-specific ventricular
      flow with the presence of both mitral and aortic valves. 

PMID- 24109785
TI  - Numerical simulation and hemodynamic analysis of the modified Blalock-Taussig
      shunt.
AB  - The modified Blalock-Taussig (mB-T) shunt is an effective palliative surgical
      method in the treatment of cyanotic congenital heart diseases. It increases the
      pulmonary blood flow through an implanted shunt between systemic and pulmonary
      arteries. The surgical technique improved over the years. However, it is still a
      challenge to control appropriate distribution of blood flow through this shunt
      after this kind of procedure till now. Here, we report on the method of
      computational fluid dynamics (CFD) for the hemodynamic studies of a patient
      specific case after the mB-T shunt. The analysis system that we validated
      previously in the studies of the Norwood procedure was applied to predict the
      hemodynamic characteristics in the mB-T hunt area. The real-time velocities
      derived from Echocardiography measurements and the blood pressure wave
      reflections from peripheral vessels were utilized as boundary conditions to
      physiologically capture the blood flow information in the simulation. The local
      pressure, blood flow distribution and wall shear stress were calculated. The
      results suggest pressure decreases greatly through the shunt and around 40% of
      blood flow is distributed from the systemic circulation to pulmonary arteries in
      one cardiac cycle. These indict computational hemodynamics may be applied in
      future studies of establishing quantitative standards to evaluate the outcomes of
      the mB-T shunt and to optimize the implantation of the mB-T shunt in virtual
      surgeries. 

PMID- 24109786
TI  - Simulation of transcatheter aortic valve implantation under consideration of
      leaflet calcification.
AB  - Transcatheter aortic valve implantation (TAVI) is a minimally invasive off-pump
      procedure to replace diseased aortic heart valves. Known complications include
      paravalvular leaks, atrioventricular blocks, coronary obstruction and annular
      rupture. Careful procedure planning including appropriate stent selection and
      sizing are crucial. Few patient-specific geometric parameters, like annular
      diameters, annular perimeter and measurement of the distance to the coronary
      ostia, are currently used within this process. Biomechanical simulation allows
      the consideration of extracted anatomy and material parameters for the
      intervention, which may improve planning and execution phases. We present a
      simulation workflow using a fully segmented aortic root anatomy, which was
      extracted from pre-operative CT-scan data and apply individual material models
      and parameters to predict the procedure outcome. Our results indicate the high
      relevance of calcification location and size for intervention planning, which are
      not sufficiently considered at this time. Our analysis can further provide
      guidance for accurate, patient-specific device positioning and future adaptations
      to stent design. 

PMID- 24109788
TI  - Detection of growth-restricted fetuses using a patient-specific model.
AB  - Fetal growth restriction (FGR) is one of the major contributors to adverse
      perinatal outcome. The purpose of this work was to extend the use of Ultrasound
      Doppler measurements and allow early and accurate detection of FGR. To this end,
      a mathematical model was developed to represent the major fetal hemodynamic
      mechanisms involved. Based on model parameters' values, the forward model
      predicted flow waveforms at the locations where Doppler measurements are
      routinely performed. Blood velocity waveforms measured in 20 FGR and 20 normal
      fetuses were used as inputs to an inverse model solution to obtain the
      parameters' values of the specific fetus. Model predictions indicated significant
      changes in the circulation of FGR fetuses compared to normal fetuses. Estimated
      cardiac output was significantly lower in the FGR group compared to the control
      group (330 +/- 52 ml min(-1) Kg(-1) compared to 396 +/- 52 ml min(-1) Kg(-1),
      P<0.001). Also, estimated cardiac output distribution towards the placenta was
      lower for the FGR group (145 +/- 49 ml min(-1) Kg(-1) compared to 181 +/- 31 ml
      min(-1) Kg(-1), P<0.01). In the FGR group the model indicated also significant
      increase in estimated cardiac output distribution towards the brain (9.6 +/-
      0.7%, compared to 8.0 +/- 1.6 %, P<0.01) and in the degree of blood shunted by
      the ductus venosus (60.6 +/- 17.7 %, compared to 39.7 +/- 14.8 %, P<0.01),
      indicating severe brain-sparing state in these fetuses. We conclude that patient
      specific mathematical modeling is a promising direction for personalizing and
      optimizing the treatment options in pregnancies complicated by fetal growth
      restriction.

PMID- 24109787
TI  - A novel dynamic cardiac simulator utilizing pneumatic artificial muscle.
AB  - With the development of methods and skills of minimally invasive surgeries,
      equipments for doctors' training and practicing are in high demands. Especially
      for the cardiovascular surgeries, operators are requested to be familiar with the
      surgical environment of a beating heart. In this paper, we present a new dynamic
      cardiac simulator utilizing pneumatic artificial muscle to realize heartbeat.
      It's an artificial left ventricular of which the inner chamber is made of
      thermoplastic elastomers (TPE) with an anatomical structure of the real human
      heart. It is covered by another layer of material forming the artificial muscle
      which actuates the systole and diastole uniformly and omnidirectionally as the
      cardiac muscle does. Preliminary experiments were conducted to evaluate the
      performance of the simulator. The results indicated that the pressure at the
      terminal of the aorta could be controlled within the range of normal human
      systolic pressure, which quantitatively validated the new actuating mode of the
      heart-beating is effective. 

PMID- 24109789
TI  - Relationships between local geometrical features and hemodynamic flow properties.
AB  - Stroke is among the leading causes of death and disability worldwide. Most
      strokes are ischemic, mostly caused by the blockage of a cerebral artery by a
      thrombotic embolus. Carotid atherosclerosis and the subsequent plaque rupture can
      be a major source of these emboli. It is well known that blood flow affects where
      atherosclerotic plaque will arise. In particular, vascular wall shear stress
      (WSS) has been linked to the initiation and progression of carotid plaque.
      However, it is difficult to measure WSS in vivo and it is time-consuming to
      compute WSS using computational fluid dynamics packages. The goals of this paper
      are (i) to identify a set of local geometric parameters that are correlated with
      WSS and (ii) to develop a regression model to predict WSS from the geometric
      parameters. We validated our regression model using the root mean squared error
      (RMSE), adjusted R(2) and Akaike information criterion (AIC). The experimental
      study involved six carotid arteries with the internal and external carotid
      arteries (ICA and ECA respectively) analyzed separately. The adjusted R(2)s for 9
      of the 12 branches were higher than 0.8. Since the proposed local geometric
      parameters can be obtained efficiently, these parameters can potentially be used
      as carotid disease phenotypes that will allow for a much more cost-effective
      method to identify subjects with elevated stroke risk. 

PMID- 24109790
TI  - A novel coupling algorithm for computing blood flow in viscoelastic arterial
      models.
AB  - We propose a novel coupling algorithm, based on the operator-splitting scheme,
      which implements the viscoelastic wall law at the coupling nodes of the vessels.
      Two different viscoelastic models are used (V1 and V2), leading to five different
      computational setups: elastic wall law, model V1 applied at interior and coupling
      grid points, model V1 applied only at the interior grid points (V1-int), model V2
      applied at interior and coupling grid points, model V2 applied only at the
      interior grid points (V2-int). These have been tested with two arterial
      configurations: (i) single artery, and (ii) complete arterial tree. Models V1-int
      and V2-int lead to incorrect conclusions and to errors which can be of the same
      order as, and are at least 1/5 of, the difference between the results with the
      elastic and the viscoelastic laws. Both test cases demonstrate the importance of
      modeling the viscous component of the pressure-area relationship at all grid
      points, including the coupling points between vessels or at the inlet/outlet of
      the model. 

PMID- 24109791
TI  - Estimation of aortic pressure waveforms from 4D phase-contrast MRI.
AB  - Several approaches for the non-invasive MRI-based measurement of the aortic
      pressure waveform over the heart cycle have been proposed in the last years.
      These methods are normally based on time-resolved, two-dimensional phase-contrast
      sequences with uni-directionally encoded velocities (2D PC-MRI). In contrast,
      three-dimensional acquisitions with tridirectional velocity encoding (4D PC-MRI)
      have been shown to be a suitable data source for detailed investigations of blood
      flow and spatial blood pressure maps. In order to avoid additional MR
      acquisitions, it would be advantageous if the aortic pressure waveform could also
      be computed from this particular form of MRI. Therefore, we propose an approach
      for the computation of the aortic pressure waveform which can be completely
      performed using 4D PC-MRI. After the application of a segmentation algorithm, the
      approach automatically computes the aortic pressure waveform without any manual
      steps. We show that our method agrees well with catheter measurements in an
      experimental phantom setup and produces physiologically realistic results in
      three healthy volunteers. 

PMID- 24109792
TI  - An hemodynamic work bench for in-vitro measurements in arterial bifurcations:
      experimental results and comparison with the output of a simplified CFD model.
AB  - To quantify fluid-structure interactions in arterial walls, from a biomechanical
      standpoint, a complete characterization of blood flow, shear stress in the
      interface between blood and endothelium, wall elasticity and wall stresses
      distribution are needed. 

PMID- 24109793
TI  - Characterization of pressure reduction in coil-filled aneurysm under flow of
      human blood with and without anti-coagulant.
AB  - Filling aneurysms with embolization coils is a widely used part of the treatment
      to stop intracranial aneurysm from rupturing. However, the effect of coiling on
      aneurysmal pressure has not been established. In this study, the effect of intra
      aneurysmal coiling on pressure reduction was characterized. Coil deployment in
      the aneurysm will disturb flow and may induce aneurysmal coagulation. These
      effects were experimentally examined in this study using silicone rubber saccular
      aneurysm models. Changes in aneurysmal blood pressure under pulsatile flow were
      characterized. With coils in the aneurysm, results showed that flow reduction of
      anti-coagulated blood in the aneurysm did not reduce aneurysmal pressure.
      Significant pressure reduction was observed only when the blood's coagulation
      ability is restored to normal. These results suggest that blood coagulation is
      pivotal to pressure reduction and concomitant with rupture risk reduction in
      treatments of aneurysm with coils. 

PMID- 24109795
TI  - Neural recording front-end IC using action potential detection and analog buffer
      with digital delay for data compression.
AB  - This paper presents a neural recording analog front-end IC intended for
      simultaneous neural recording with action potential (AP) detection for data
      compression in wireless multichannel neural implants. The proposed neural
      recording front-end IC detects the neural spikes and sends only the preserved AP
      information for wireless transmission in order to reduce the overall power
      consumption of the neural implant. The IC consists of a low-noise neural
      amplifier, an AP detection circuit and an analog buffer with digital delay. The
      neural amplifier makes use of a current-reuse technique to maximize the
      transconductance efficiency for attaining a good noise efficiency factor. The AP
      detection circuit uses an adaptive threshold voltage to generate an enable signal
      for the subsequent functional blocks. The analog buffer with digital delay is
      employed using a finite impulse response (FIR) filter which preserves the AP
      waveform before the enable signal as well as provides low-pass filtering. The
      neural recording front-end IC has been designed using standard CMOS 0.18-um
      technology occupying a core area of 220 um by 820 um. 

PMID- 24109796
TI  - Multicoil resonance-based parallel array for smart wireless power delivery.
AB  - This paper presents a novel resonance-based multicoil structure as a smart power
      surface to wirelessly power up apparatus like mobile, animal headstage, implanted
      devices, etc. The proposed powering system is based on a 4-coil resonance-based
      inductive link, the resonance coil of which is formed by an array of several
      paralleled coils as a smart power transmitter. The power transmitter employs
      simple circuit connections and includes only one power driver circuit per
      multicoil resonance-based array, which enables higher power transfer efficiency
      and power delivery to the load. The power transmitted by the driver circuit is
      proportional to the load seen by the individual coil in the array. Thus, the
      transmitted power scales with respect to the load of the electric/electronic
      system to power up, and does not divide equally over every parallel coils that
      form the array. Instead, only the loaded coils of the parallel array transmit
      significant part of total transmitted power to the receiver. Such adaptive
      behavior enables superior power, size and cost efficiency then other solutions
      since it does not need to use complex detection circuitry to find the location of
      the load. The performance of the proposed structure is verified by measurement
      results. Natural load detection and covering 4 times bigger area than
      conventional topologies with a power transfer efficiency of 55% are the novelties
      of presented paper. 

PMID- 24109797
TI  - BaroLoop: using a multichannel cuff electrode and selective stimulation to reduce
      blood pressure.
AB  - The therapy of refractory hypertension is an increasing problem for health care
      systems and a frontend in research in both pharmacology and neuroelectronic
      engineering. Overriding the baroreceptive information of afferent nerve fibers,
      originating from pressure sensors in the aortic arch, can trigger the baroreflex,
      a systemic control system that lowers the blood pressure (BP) almost
      instantaneously. Using a multichannel cuff electrode, wrapped around a rat vagal
      nerve, we were able to regulate the BP using selective, tripolar stimulation. The
      tripolar stimulation was sufficiently selective to not trigger any unwanted side
      effects like bradycardia or bradypnea. The BP was reduced best with charge
      balanced stimulation amplitudes of 1 mA and pulse duration of 0.3 ms. The
      stimulation frequency had only a mild influence on the effectiveness of the
      stimulation and did work best at 40 Hz. We found that the BP took up to five
      times the stimulation period to recover to the value prior to stimulation. 

PMID- 24109798
TI  - Materials design considerations involved in the fabrication of implantable
      bionics by metallization of ceramic substrates.
AB  - The Pt metallization of co-fired Al2O3/SiO2 substrates containing Pt feedthroughs
      was shown to be a suitable means to construct implantable bionics. The use of
      forge welding to join an electrode to such a metallized feedthrough was
      demonstrated and subsequently evaluated through the use of metallography and
      electron microscopy. Metallurgical phenomena involved in forge welding relevant
      to the fabrication of all types of biomedical implants are discussed within this
      paper. The affect of thermal profiles used in brazing or welding to build
      implantable devices from metal components is analysed and the case for considered
      selection of alloys in implant design is put forward. 

PMID- 24109799
TI  - Hybrid EEG and eye movement interface to multi-directional target selection.
AB  - This work addresses the development of a low-cost hybrid interface with eye
      tracking and brain signals. Eye movement detection is used for search task and
      EEG-based brain computer interface (BCI) for selection task. Multi-directional
      target selection experiments with the hybrid interface device were conducted with
      five subjects to evaluate the proposed hybrid interface scheme. The task asked
      each user to move a cursor onto a circular target among twelve possible positions
      and select it. Using the Fitts' law, the interface performance was compared with
      the computer mouse. With two BCI selection confirmation schemes, the hybrid
      interface attained 2-2.7 bit/s overall. Based on the results, the potential of
      the proposed hybrid interface was discussed. 

PMID- 24109800
TI  - Droplet backside exposure for making slanted SU-8 microneedles.
AB  - This paper presented a droplet backside exposure (DBE) method for making slanted
      microneedle structures on a flexible polymer substrate. To demonstrate the
      feasibility of the DBE approach, SU-8 microneedle arrays were fabricated on
      polydimethylsiloxane (PDMS) substrates. The length of the microneedles was
      controlled by tuning the volume of the SU-8 droplet, utilizing the wetting
      barrier phenomenon at a liquid-vapor-hydrophilic surface-hydrophobic surface
      interface. The experimental results showed excellent repeatability and
      controllability of the DBE method for microneedle fabrication. Analytical models
      were also studied to predict the dimensions of the microneedles, which agreed
      with the experimental data. 

PMID- 24109801
TI  - Spiral peripheral nerve interface; updated fabrication process of the
      regenerative implant.
AB  - The spiral peripheral nerve interface (SPNI) has been developed to record neural
      activity by utilizing the body's own ability to regenerate axons after injury.
      The implantable device is capable of providing a chronic recording array for use
      with technology designed to compensate for a loss of motor function. The SPNI
      offers a good route to establishing an effective interface to the peripheral
      nervous system (PNS) as the signals are enclosed within an insulating array that
      amplifies the axon signals for the neural recording, and reduces the amount of
      current necessary for stimulation. This paper presents an updated fabrication
      process that addresses the problems of previous designs and allows for an easier
      integration to external electronics via a ball-bonding technique. The updated
      device has been tested electrically in vitro, to show that it is capable of
      providing a reliable electrical interface to the regenerated tissue. 

PMID- 24109802
TI  - Misalignment tolerable coil structure for biomedical applications with wireless
      power transfer.
AB  - Coil-misalignment is one of the major hurdles for inductively coupled wireless
      power transfer in applications like retinal prosthesis. Weak magnetic flux
      linkage due to coil misalignments would significantly impair the power
      efficiency. A novel receiver configuration with high misalignment tolerance is
      presented in this paper. The proposed receiver is composed of two receiver coils
      placed orthogonally, so as to reduce the variation of mutual inductance between
      transmitting and receiving coils under misalignment conditions. Three different
      receiver coil structures are analyzed and compared using the same length of wire.
      Theoretical predictions have been confirmed with measurement results. 

PMID- 24109803
TI  - A multichannel integrated circuit for neural spike detection based on EC-PC
      threshold estimation.
AB  - In extracellular neural recording experiments, spike detection is an important
      step for information decoding of neuronal activities. An ASIC implementation of
      detection algorithms can provide substantial data-rate reduction and facilitate
      wireless operations. In this paper, we present a 16-channel neural spike
      detection ASIC. The chip takes raw data as inputs, and outputs three data streams
      simultaneously: field potentials down sampled at 1.25 KHz, band-pass filtered
      neural data, and spiking probability maps sampled at 40 KHz. The functionality
      and the performance of the chip have been verified in both in-vivo and benchtop
      experiments. Fabricated in a 0.13 um CMOS process, the chip has a peak power
      dissipation of 85 uW per channel and achieves a data-rate reduction of 98.44%. 

PMID- 24109804
TI  - Current amplitude-dependent modulation of rotational behavior with GPi
      stimulation in the rodent model of Parkinson's Disease.
AB  - The globus pallidus interna (GPi) is the main output nucleus of the basal
      ganglia, the neural circuit involved in motor and cognitive performance which is
      impacted by Parkinson's Disease (PD). Although deep brain stimulation (DBS) of
      the GPi is an effective treatment for the motor symptoms of PD in humans, the
      link between the stimulation signal space and the therapeutic benefits of DBS is
      not well understood. The rodent model of PD is useful for characterization of
      ameliorative DBS, though prior work focuses on the rodent model for DBS of the
      subthalamic nucleus (STN). This work investigates GPi-DBS in the rat model of PD
      under the framework of an amphetamine-induced rotational behavior. This work
      elucidates the relationship between stimulation current intensity and the motor
      effects of the dopaminergic lesion. Our results show that rotational behavior is
      modulated by the current intensity and validates GPi-DBS as a beneficial
      treatment of PD. 

PMID- 24109806
TI  - Analysis of fractal electrodes for efficient neural stimulation.
AB  - Planar electrodes are increasingly used in a variety of neural stimulation
      techniques such as epidural spinal cord stimulation, epidural cortical
      stimulation, transcranial direct current stimulation and functional electric
      stimulation. Recently, optimized electrode geometries have been shown to increase
      the efficiency of neural stimulation by maximizing the variation of current
      density on the electrode surface. In the present work, a new family of modified
      fractal electrode geometries is developed to increase the neural activation
      function and enhance the efficiency of neural stimulation. It is hypothesized
      that the key factor in increasing the activation function in the tissue adjacent
      to the electrode is to increase the "edginess" of the electrode surface, a
      concept that is explained and quantified by fractal mathematics. Rigorous finite
      element simulations were performed to compute the distribution of electric
      potential produced by proposed geometries, demonstrating that the neural
      activation function was significantly enhanced in the tissue. The activation of
      800 model axons positioned around the electrodes was also quantified, showing
      that modified fractal geometries yielded a 22% reduction in input power
      consumption while maintaining the same level of neural activation. The results
      demonstrate the feasibility of increasing stimulation efficiency using modified
      fractal geometries beyond the levels already reported in the literature. 

PMID- 24109805
TI  - A programmable analog subthreshold biomimetic model for bi-directional
      communication with the brain.
AB  - In this paper, we present a hardware implementation of a second order Laguerre
      Expansion of Volterra Kernel (LEV) model with four basis functions. The model is
      versatile enough to be applied at different abstraction levels (synapse, neuron,
      or network of neurons) and is implemented with analog building blocks in a
      modular manner. These analog blocks, realized using low power subthreshold CMOS
      transistors, can serve as a basis for large-scale hardware systems that emulate
      multi-input multi-output (MIMO) spike transformations in populations of neurons.
      The normalized mean square error between the signals produced by the circuit LEV
      implementation and the ideal LEV model is 8.15%. The total power consumption of
      the analog circuitry is less than 33nW. 

PMID- 24109807
TI  - Calculating the induced electromagnetic fields in real human head by deep
      transcranial magnetic stimulation.
AB  - Stimulation of deeper brain structures by transcranial magnetic stimulation (TMS)
      may be beneficial in the treatment of several neurological and psychiatric
      disorders. This paper presents numerical simulation of deep transcranial magnetic
      stimulation (dTMS) by considering double cone, H-and Halo coils. Three
      dimensional distributions of the induced fields i.e. magnetic flux density,
      current density and electric fields in realistic head model by dTMS coils were
      calculated by impedance method and the results were compared with that of figure
      of-eight coil. It was found that double cone and H-coils have significantly deep
      field penetration at the expense of induced higher and wider spread electrical
      fields in superficial cortical regions. The Halo coil working with a circular
      coil carrying currents in opposite directions provides a flexible way to
      stimulate deep brain structures with much lower stimulation in superficial brain
      tissues. 

PMID- 24109808
TI  - An in vitro demonstration of CMOS-based optoelectronic neural interface device
      for optogenetics.
AB  - A CMOS-based neural interface device equipped with an integrated micro light
      source array for optogenetics was fabricated and demonstrated. A GaInN LED array
      formed on sapphire substrate was successfully assembled with a multifunctional
      CMOS image sensor that is capable of on-chip current injection. We demonstrated a
      functionality of light stimulation onto ChR2-expressed cells in an in vitro
      experiment. A ChR2-expressed cell were successfully stimulated with the light
      emitted from the fabricated device. 

PMID- 24109809
TI  - Habituation of steady-state visual evoked potentials in response to high
      frequency polychromatic foveal visual stimulation.
AB  - In an attempt to develop safe and robust methods for monitoring migraineurs'
      brain states, we explores the feasibility of using white, red, green and blue LED
      lights flickering around their critical flicker fusion (CFF) frequencies as
      foveal visual stimuli for inducing steady-state visual evoked potentials (SSVEP)
      and causing discernible habituation trends. After comparing the habituation
      indices, the multi-scale entropies and the time dependent intrinsic correlations
      of their SSVEP signals, we reached a tentative conclusion that sharp red and
      white light pulses flickering barely above their CFF frequencies can replace
      commonly used 13Hz stimuli to effectively cause SSVEP habituation among normal
      subjects. Empirical results showed that consecutive short bursts of light can
      produce more consistent responses than a single prolonged stimulation. Since
      these high frequency stimuli do not run the risk of triggering migraine or
      seizure attacks, further tests of these stimuli on migraine patients are
      warranted in order to verify their effectiveness. 

PMID- 24109810
TI  - Photodynamic cell membrane perforation for intracellular electrodes.
AB  - We report a new aspect of rapid (<10 seconds) light-induced cell membrane
      perforation for intracellular electrode by Hematoporphyrin (HP), which is an
      original photosensitizer for photodynamic therapy concept. A microelectrode
      insertion process to cell could be improved by pinpoint use of the
      photosensitizing effect to degenerate cell membranes prior to insertion.
      According to the concept, simple electrode coating with photosensitizer will
      enable intracellular electrode array for neural engineering. 

PMID- 24109811
TI  - Fundamental short-term memory of semi-artificial neuronal network.
AB  - Spatiotemporal pattern of neuronal network activity is a key component of brain
      information processing. Cultured rat hippocampal neurons on the multielectrodes
      array dish are suitable for analyzing and manipulating network dynamics and its
      developmental changes. We applied paired electrical inputs at various inter
      stimulus intervals (ISi) and analyzed the spatio-temporal pattern of evoked
      responses. We found that the pattern of evoked electrical activity was affected
      by existence of a prior input in the case that ISi of paired stimuli was within 2
      s. These results suggest that a semi-artificial neuronal network on a culture
      dish has a fundamental component of short-term memory, and the origin of this
      hysteresis is transition among the internal states of the network, undertaken by
      synaptic transmissions. 

PMID- 24109812
TI  - Anatomical variability predicts individual differences in transcranial electric
      stimulation motor threshold.
AB  - We have proposed that the current amplitude in electroconvulsive therapy (ECT) be
      lowered to produce stimulation closer to the neural activation threshold and
      individualized to account for anatomical variability across patients. A novel
      approach to individualize the ECT current amplitude could be via motor threshold
      (MT) determination with transcranial electric stimulation (TES) applied through
      the ECT electrodes instead of the fixed high current approach. This study derives
      an estimate of the electric field (E-field) neural activation threshold and tests
      whether individual differences in TES MT are explained by anatomical variability
      measurements and simulations in individual head models. The E-field distribution
      induced by a right unilateral (RUL) ECT electrode configuration was computed in
      subject-specific finite element head models of four nonhuman primates (NHPs) for
      whom MT was measured. By combining the measured MTs and the computed E-field
      maps, the neural activation threshold is estimated to be 0.45 +/- 0.07 V/cm for
      0.2 ms stimulus pulse width. The individual MT was correlated with the electrode
      to-cortex distance under the superior electrode (R(2)=.96, p=.022) as well as
      with the simulated electrode-current/induced-E-field ratio (R(2)=.95, p=.026),
      indicating that both anatomical measurements and computational models could
      predict the individual current requirements for transcranial stimulation. These
      findings could be used with realistic human head models and in clinical studies
      to explore novel ECT dosing paradigms, and as a new noninvasive means to
      determine individual dosage requirement with ECT. 

PMID- 24109813
TI  - Comparison of three right-unilateral electroconvulsive therapy montages.
AB  - The efficacy and cognitive outcomes of electroconvulsive therapy (ECT) on
      psychiatric disorders have been shown to depend on variations in electrode
      montages. Conventionally, the right-unilateral (RUL) montage was temporoparietal,
      originally proposed by d'Elia. Although it was reported to have better cognitive
      outcomes than the bitemporal montage, it is still associated with substantial
      memory side effects. Two other RUL montages utilizing a frontal electrode, also
      proposed by d'Elia, may be more beneficial. In order to investigate this, a high
      resolution finite element human head model was generated from MRI scans and
      implemented with tissue heterogeneity. The model was used to compare the effects
      of three different d'Elia RUL montages. The results suggest that the two
      alternative placements are likely to result in lesser memory side effects, and
      may have useful efficacy. 

PMID- 24109814
TI  - Inconsistent outcomes of transcranial direct current stimulation (tDCS) may be
      originated from the anatomical differences among individuals: a simulation study
      using individual MRI data.
AB  - Transcranial direct current stimulation (tDCS) is a kind of neuromodulation
      protocol, which transmits small amount of DC currents through scalp electrodes to
      facilitate or inhibit particular areas of the brain. Although many studies have
      demonstrated that tDCS can effectively modulate excitability of various brain
      sites, the outcomes of the tDCS treatment are not consistent among subjects to
      whom identical electrode montages were applied. So far, no studies have clearly
      elucidated the main cause of this individual variability. The hypothesis of our
      study was that the individual variability in the tDCS effect might be originated
      due to the anatomical differences among subjects. To verify our hypothesis, we
      investigated the relationship between the current density value at dorsolateral
      prefrontal cortex (DLPFC) simulated using finite element method (FEM) and the
      behavioral outcomes of a simple working memory (WM) task. A 3-back WM task
      experiment was conducted with twenty-five healthy subjects before and after the
      DC stimulation, when the cathode and anode electrodes were attached to right
      supraorbital area and F3 location, respectively, for all subjects. The results
      showed that participants who showed enhanced WM task performance after tDCS had a
      significantly larger current density on DLPFC, suggesting that the inconsistent
      behavioral outcomes of tDCS might be partially due to the anatomical differences
      among subjects. 

PMID- 24109815
TI  - A low emission, low power non-linear frequency modulation based transmitter for
      implanted devices.
AB  - The paper proposes a low emission, non linear frequency modulator for
      transmitting neural signals. With the advent of embedded medical devices,
      designers need to start developing low Electromagnetic Interference (EMI) and
      Radio Frequency Interference (RFI) devices. We propose a non-phase locked loop
      based frequency modulator. The modulator utilizes a ramp to encode the bit stream
      from the neural amplifier. In addition it utilizes a non linear signal to
      modulate the encoded signal leading to lowering of peak of power spectrum, a
      measure of electro-magnetic interference. The proposed algorithm has been
      implemented on 0.18u AMS technology and results presented. 

PMID- 24109816
TI  - A synchronization method for wireless acquisition systems, application to brain
      computer interfaces.
AB  - A synchronization method for wireless acquisition systems has been developed and
      implemented on a wireless ECoG recording implant and on a wireless EEG recording
      helmet. The presented algorithm and hardware implementation allow the precise
      synchronization of several data streams from several sensor nodes for
      applications where timing is critical like in event-related potential (ERP)
      studies. The proposed method has been successfully applied to obtain visual
      evoked potentials and compared with a reference biosignal amplifier. The control
      over the exact sampling frequency allows reducing synchronization errors that
      will otherwise accumulate during a recording. The method is scalable to several
      sensor nodes communicating with a shared base station. 

PMID- 24109817
TI  - Design of a high voltage stimulator chip for a stroke rehabilitation system.
AB  - This paper describes the design of an 8-channel high voltage stimulator chip for
      rehabilitation of stroke patients through surface stimulation, which requires
      high stimulation currents and high compliance voltage. The chip gets stimulation
      control data through its Serial Peripheral Interface (SPI), and can accordingly
      generate biphasic stimulation currents with different amplitudes, duration,
      frequencies and polarities independently for each channel. The current driver is
      implemented with thick oxide devices with a supply voltage up to 90V. The chip is
      designed in a 0.35epsilonm X-FAB high voltage process. 

PMID- 24109818
TI  - Source localization techniques for direction decoding from local field
      potentials.
AB  - Local Field Potential (LFP) recordings are one type of intracortical recordings,
      (besides Single Unit Activity) that can help decode movement direction
      successfully. In the longterm however, using LFPs for decoding presents some
      major challenges like inherent instability and non-stationarity. Our approach to
      overcome this challenge bases around the hypothesis that each task has a
      signature source-location pattern. The methodology involves introduction of
      source localization, and tracking of sources over a period of time that enables
      us to decode movement direction in an eight-direction center-out-reach-task. We
      establish that such tracking can be used for long term decoding, with preliminary
      results indicating consistent patterns. In fact, tracking task related source
      locations render up to 66% accuracy in decoding movement direction one week after
      the decoding model was learnt. 

PMID- 24109819
TI  - Microfluidic device with dual mechanical cues for cell migration investigation.
AB  - Cell migration plays an important role in numerous physiological and pathological
      conditions, such as angiogenesis, wound healing and cancer metastasis.
      Understanding the fundamental mechanisms of cell migration is crucial to develop
      strategies for disease treatment and regenerative medicine. Several biomechanical
      cues have been well studied about their effects on guiding cell migration.
      However, the effects of dual or multiple cues on cell migration are barely
      addressed. In this work, we developed a microfluidic-based device to study the
      combinatory effects of osmotic and stiffness gradient on cell migration. Computer
      simulation and experimental validation showed that the device was capable of
      providing stable osmotic and stiffness gradient to cultured cells at the same
      time. Preliminary results suggest that our device has a valuable potential in
      studying cell migration in complex conditions which better recapitulate the
      complex environmental conditions in vivo. 

PMID- 24109821
TI  - Biological effects of ultrasound stimulus on cells derived from human ovarian
      follicular liquid.
AB  - Low-Intensity Pulsed Ultrasound Stimulus (LIPUS) accelerates the bone fracture
      healing in animal models and in clinical studies. In this work, according to the
      literature, we have chosen the mesenchymal stem cells (MSCs) as precursors of
      bony tissue, in particular the MSCs derived from the human ovarian follicular
      liquid (FL), and we have investigated the effects of ultrasounds on their
      proliferation. We tested two different durations of ultrasound stimulus (2 and 5
      min) and compared these data to the control without ultrasound treatment. To
      quantify the proliferation of these putative MSCs, we used the BrdU incorporation
      assay: in comparison with the control, the results showed that 5 min of
      ultrasound stimulus significantly increased the percentage number of cells in
      intensive proliferative activity; on the other hand, there was no significant
      difference using 2 min of stimulation, hypothetically because the transmitted
      energy was not sufficient to stimulate the cells and to consequently enhance
      their proliferation. In conclusion, the effects of LIPUS on putative MSCs derived
      from ovarian follicular liquid show potential developments in biotech or medical
      applications. 

PMID- 24109820
TI  - Ultrasound stimulus to enhance the bone regeneration capability of gelatin
      cryogels.
AB  - In the present study, gelatin-based cryogels have been seeded with human SAOS-2
      osteoblasts. In order to overcome the drawbacks associated with in vitro culture
      systems, such as limited diffusion and inhomogeneous cell-matrix distribution,
      this work describes the application of ultrasounds (average power, 149 mW;
      frequency, 1.5 MHz) to physically enhance the cell culture in vitro. The results
      indicate that the physical stimulation of cell-seeded gelatin-based cryogels
      upregulates the bone matrix production. 

PMID- 24109822
TI  - Effects of the hydrostatic pressure in in vitro beating cardiac syncytia in terms
      of kinematics (kinetic energy and beat frequency) and syncytia geometrical
      functional classification.
AB  - Many important observations and discoveries in heart physiology have been made
      possible using the isolated heart method of Langendorff, e.g. the discovery of
      the very famous Frank-Starling law of the heart. Nevertheless, the Langendorff's
      method has some limitations and disadvantages such as the probability of
      preconditioning and a high oxidative stress, leading to the deterioration of the
      contractile function. To avoid the preceding drawbacks associated to the use of a
      whole heart, we have alternatively used beating mouse cardiac syncytia cultured
      in vitro in order to assess the ergotropic and chronotropic effects of both
      increasing and decreasing hydrostatic pressures. To achieve the preceding aim, we
      have developed a method based on image processing analysis to evaluate the
      kinematics of that pressure-loaded beating syncytia starting from the video
      registration of their contraction movement. We have verified the Frank-Starling
      law of the heart in in vitro beating cardiac syncytia and we have obtained their
      geometrical-functional classification. The present method could be used in in
      vitro studies of beating cardiac patches, as alternative to the Langendorff's
      heart in biochemical, pharmacological, and physiology studies, and, especially,
      when the Langendorff's technique is inapplicable. Furthermore, the method could
      help, in heart tissue engineering and bioartificial heart researches, to
      "engineer the heart piece by piece". 

PMID- 24109823
TI  - Evaluation of strontium introduced apatite cement as the injectable bone
      substitute developments.
AB  - We have developed bone cement introducing Strontium (Sr) to promote early bone
      regeneration. To prolong the release duration of Sr, we applied inorganic Sr
      filler for containing into the cement powder. The purpose of this study is to
      evaluate the mechanical properties, crystallinic properties, and ion release
      activities, especially Sr anion, of this cement. Alpha-TCP powder was mixed with
      Sr filler, with 0.1wt%, 0.5wt%, 1.0wt%, and 5.0wt%. These were mixed with mixing
      liquid and formed for each test. They were incubated and crystalized in 95%
      moisture for 1 week. The mechanical properties were studied by the compression,
      the diametral tensile strength and 4-point vending. Tested specimens were
      evaluated by X-ray diffraction(XRD) and scanning electron microscopic(SEM)
      imaging. The ion release behaviors were measured by inductively coupled plasma
      mass spectrometry(ICP-MS). The mechanical properties were increased in
      consistency of filler, but decreased in some samples because of declining the
      apatite matrix. And the Sr release showed interesting results as the sequential
      resource of Sr. By adjusting the mixing ratio or considering the application of
      these Sr releasable cements, this material would show good performance by its
      strength and longer Sr release for bone regeneration. 

PMID- 24109824
TI  - Low cost, patterning of human hNT brain cells on parylene-C with UV & IR laser
      machining.
AB  - This paper describes the use of 800nm femtosecond infrared (IR) and 248nm
      nanosecond ultraviolet (UV) laser radiation in performing ablative micromachining
      of parylene-C on SiO2 substrates for the patterning of human hNT astrocytes.
      Results are presented that support the validity of using IR laser ablative
      micromachining for patterning human hNT astrocytes cells while UV laser radiation
      produces photo-oxidation of the parylene-C and destroys cell patterning. The
      findings demonstrate how IR laser ablative micromachining of parylene-C on SiO2
      substrates can offer a low cost, accessible alternative for rapid prototyping,
      high yield cell patterning. 

PMID- 24109826
TI  - Admittance control scheme for implementing model-based assistance-as-needed on a
      robot.
AB  - A model-based assistance-as-needed paradigm has been developed to govern the
      assistance provided by an assistive robot to its operator. This paradigm has
      advantages over existing methods of providing assistance-as-needed for
      applications such as robotic rehabilitation. However, implementation of the model
      based paradigm requires a control scheme to be developed which controls the robot
      so as to provide the assistance calculated by the model-based paradigm to its
      operator. In this paper an admittance control scheme for providing model-based
      assistance-as-needed is presented. It is developed considering its suitability
      for human-robot interaction, and its role within the model-based assistance-as
      needed framework. Results from the control implemented on an example robot showed
      it is capable of providing the operator with the desired level of assistance as
      governed by the model-based paradigm. This is an essential requirement for the
      paradigm to be capable of providing efficacious assistance-as-needed in
      applications such as robotic rehabilitation. 

PMID- 24109825
TI  - Experimental evaluation of a model-based assistance-as-needed paradigm using an
      assistive robot.
AB  - In robotic rehabilitation a promising paradigm is assistance-as-needed. This is
      because it promotes patient active participation which is essential for neuro
      rehabilitation. A model-based assistance-as-needed paradigm has been developed
      which utilizes a musculoskeletal model representing the subject to calculate
      their assistance needs. In this paper we experimentally evaluate this model-based
      paradigm to control an assistive robot and provide a subject with assistance-as
      needed at the muscular level. A subject with impairments defined in specific
      muscle groups performs a number of upper limb tasks, whilst receiving assistance
      from a robotic exoskeleton. The paradigm is evaluated on its ability to provide
      assistance only as the subject needs, depending on the tasks being performed and
      the impairments defined. Results show that the model-based assistance-as-needed
      paradigm was relatively successful in providing assistance when it was needed. 

PMID- 24109827
TI  - Low-cost implementation of a self-paced treadmill by using a commercial depth
      sensor.
AB  - A self-paced treadmill that can simulate overground walking has the potential to
      improve the effectiveness of treadmill training for gait rehabilitation. We have
      implemented a self-paced treadmill without the need for expensive equipment such
      as a motion capture system and an instrumented treadmill. For this, an
      inexpensive depth sensor, ASUS XtionTM, substitutes for the motion capture
      system, and a low-cost commercial treadmill is considered as the platform of the
      self-paced treadmill. The proposed self-paced treadmill is also convenient
      because the depth sensor does not require markers placed on user's body. Through
      pilot tests with two healthy subjects, it is quantitatively and qualitatively
      verified that the proposed self-paced treadmill achieves similar performance as
      one which utilizes a commercial motion capture system (VICON) as well as an
      instrumented treadmill. 

PMID- 24109828
TI  - Yaw rate and linear velocity stabilized manual wheelchair.
AB  - We present the development of a prototype novel low-power, inexpensive stability
      control system for manual wheelchairs. Manual wheelchairs, while providing the
      ability to maneuver in relatively small indoor spaces, have a high center of
      gravity making them prone to tipping. Additionally, they can easily slide on
      sloped surfaces and can even spin and tip when attempting to turn or brake too
      quickly. When used on ramps and in outdoor environments where the surface is
      rarely perfectly flat (slopes greater than 1?20 (5%) are common), wheelchair
      users can easily encounter potentially dangerous situations. The design and
      evaluation of an accident prevention system for independent manual wheelchair
      users that increases independence by enabling mobility with greater confidence
      and safety is described. The system does not limit a wheelchair user's ability to
      manually brake, rather, if the system detects that the wheelchair is out of
      control, braking force will be added by the system to either one or both wheels.
      The prototype utilized inexpensive bicycle technologies for the wheel brake and
      electrical power generator assemblies. Custom servos were designed along with
      custom electronics and firmware in the prototype to evaluate performance. The
      goal of the project was to derive specifications for a control and actuation
      system that utilizes inexpensive bicycle components in this cost-sensitive
      application. The design is detailed and the final specifications provided. 

PMID- 24109829
TI  - Proposal of bioinstrumentation using shape deformation of amputated upper limb.
AB  - Some upper limb amputees have been annually supplied with myoelectric prostheses
      by social rehabilitation promotion services. However, the persons supplied with
      the prostheses have been limited because a supply system has not been established
      yet. Accordingly, we propose a new bioinstrumentation using the shape deformation
      of the amputated upper limbs without using the myoelectricity generated on the
      skin of the upper limbs. The repeatability is superior to the myoelectricity
      because the shape deformation is directly measured by strain gages and also the
      cost is much superior to the myoelectricity. 

PMID- 24109830
TI  - Robot-assisted upper limb rehabilitation in chronic stroke patients.
AB  - The goal of this study is to evaluate the effects of upper limb robot-assisted
      treatment in chronic post-stroke patients using clinical outcome measures and
      kinematic parameters. Thirty-two chronic stroke patients participated in the
      study. Fugl-Meyer (FM) Assessment scale and Motricity Index (MI) were used for
      clinical assessment, and a set of kinematic parameters was computed. A
      significant decrease in motor impairment after the robotassisted treatment (FM
      p<0.001 and MI p<0.001) was found. Movement mean velocity (p<0.001) and accuracy
      (p<0.05) increased. Robotic treatment is effective to reduce motor impairment in
      chronic stroke patients. The exclusive use of clinical scales do not provide an
      exhaustive evaluation of effectiveness of treatment and our study suggests that
      kinematic parameters should be computed as well.

PMID- 24109831
TI  - Adapting the design of Anesthesia Information Management Systems to innovations
      depicted in Industrial Property documents.
AB  - The purpose of this paper is to present the design and the current development
      status of an Anesthesia Information Management System (AIMS). For this system,
      the physical and technical advances, depicted in relevant, recently published
      Industrial Property documents, have been taken into account. Additional
      innovative sensors create further data-load to be managed. Novel wireless data
      transmission modes demand eventually compliance to further proper standards, so
      that interoperability between AIMS and the existing Hospital Information Systems
      is being sustained. We attempted to define, the state-of-the-art concerning the
      functions, the design-prerequisites and the relevant standards and of an
      "emerging" AIMS that is combining hardware innovation, real-time data
      acquisition, processing and displaying and lastly enabling the necessary
      interoperability with the other components of the existing Hospital Information
      Systems. Finally, we report based on this approach, about the design and
      implementation status, of our "real-world" system under development and discuss
      the multifarious obstacles encountered during this still on-going project. 

PMID- 24109832
TI  - An efficient capacitive sensing scheme for an ophthalmic regional anesthesia
      training system.
AB  - Ophthalmic regional blocks are critical preoperative procedures involving the
      insertion of a syringe needle into the orbital cavity at such a position and
      angle that akinesia and analgesia is achieved without damage or harm to the eye
      and its associated musculature. A training system that accurately represents the
      orbital anatomical features and provides qualitative feedback on the performed
      anesthetic technique, can be of immense help in reducing risks involved in
      regional block administration. In this paper, a training system that employs a
      special but simple capacitive sensing scheme has been developed. A rapid
      prototyped eye-model has been used to ensure anatomical accuracy. Capacitive
      transmitter electrodes placed on the orbital wall along the length of the
      extraocular muscles are excited with a special excitation sequence and the
      displacement current at the needle of the syringe is measured using simple
      electronic unit and a Data Acquisition System, enabling the developed Virtual
      Instrument to detect the depth of penetration and proximity of the syringe needle
      to the ocular muscles. Additionally, the system detects needle touch of the
      muscles accurately. The proposed electrode array system and excitation schemes
      have been validated on a prototype system thus demonstrating its usefulness for
      practical training purposes. 

PMID- 24109833
TI  - Supporting management of medical equipment for inpatient service in public
      hospitals: a case study.
AB  - This work presents a study of medical equipment availability in the short and
      long term. The work is divided in two parts. The first part is an analysis of the
      medical equipment inventory for the institution of study. We consider the
      replacement, maintenance, and reinforcement of the available medical equipment by
      considering local guidelines and surveying clinical personnel appreciation. The
      resulting recommendation is to upgrade the current equipment inventory if
      necessary. The second part considered a demand analysis in the short and medium
      term. We predicted the future demand with a 5-year horizon using Holt-Winters
      models. Inventory analysis showed that 27% of the medical equipment in stock was
      not functional. Due to this poor performance result we suggested that the
      hospital gradually addresses this situation by replacing 29 non-functional
      equipment items, reinforcing stock with 40 new items, and adding 11 items not
      available in the inventory but suggested by the national guidelines. The results
      suggest that general medicine inpatient demand has a tendency to increase within
      the time e.g. for general medicine inpatient service the highest increment is
      obtained by respiratory (12%, RMSE=8%) and genitourinary diseases (20%, RMSE=9%).
      This increment did not involve any further upgrading of the proposed inventory. 

PMID- 24109834
TI  - Quantitative evaluation of cerebellar ataxia based on pathological patterns of
      the muscle activities.
AB  - Quantitative evaluation of cerebellar ataxia is crucial for precise evaluation of
      cerebellar diseases. In particular, it is essential to capture anomaly of the
      causal motor commands as well as the resultant movement for the ataxia. In this
      paper, we propose a new method to make a quantitative evaluation of the
      cerebellar ataxia based on EMG signals. As an experimental task, we asked
      subjects to perform step-tracking wrist movements with a manipulandum, and
      recorded wrist joint movements and muscle activities of four wrist prime movers
      with surface electrodes. The subjects included fourteen patients with cerebellar
      diseases and thirteen normal controls. We succeeded to extract two parameters
      from the EMG signals of the four wrist prime movers, which characterize the
      pathological patterns of muscle activities for the cerebellar ataxia, Total Co
      contraction Level (TCL) and Directionality of Muscle Activity (DMA). We found
      that the two parameters were useful to characterize pathological patterns of
      muscle activities in cerebellar ataxia. Consequently, it is expected that our
      proposed method is useful not only in tracking condition of cerebellar patients
      but also in evaluating the effects of a treatment or neuro-rehabilitation aiming
      at the normalization of motor commands. 

PMID- 24109835
TI  - Fully automatic rapid DNA Ploidy Analyzer for intraoperative rapid diagnosis
      support.
AB  - Frozen section studies are a useful method to rapidly define tumor malignancy and
      identify the extent of surgical resection. However, diagnosis with a frozen
      section is qualitative and sometimes difficult. Therefore a quantitative method
      for grading tumors is desired. We have already reported a technique of
      intraoperative flow cytometry (iFC) that supports intraoperative
      histopathological examination of frozen sections. In this study, we report an
      advanced system named "Fully Automatic Rapid DNA Ploidy Analyzer" with a tissue
      pretreatment function and a freeze-dried reagent kit for cell staining. To
      evaluate our system, we analyzed samples from glioma patients who underwent open
      surgery for brain tumors. We observed obvious difference of the Malignancy Index
      (MI) between neoplastic and perilesional brain tissue (26.0 +/-22.1% and 4.1 +/
      2.5%, respectively, P<0.001). Cut-off level for identification of the tumor in
      the biopsy specimen was 6.8% which provided 86% sensitivity and 81% specificity.
      We also obtained a good correlation between the MI and histological grade (WHO
      grading). Our new system also enabled finishing the process from sample
      preparation to the end of analysis in ten minutes or less. These results
      demonstrate that our fully automatic rapid DNA ploidy analyzer is feasible for
      rapid determination of glioma presence in a surgical biopsy sample. 

PMID- 24109836
TI  - Path tracking control of an omni-directional walker considering pressures from a
      user.
AB  - An omni-directional walker (ODW) is being developed to support the people with
      walking disabilities to do walking rehabilitation. The training paths, which the
      user follows in the rehabilitation, are defined by physical therapists and stored
      in the ODW. In order to obtain a good training effect, the defined training paths
      need to be performed accurately. However, the ODW deviates from the training path
      in real rehabilitation, which is caused by the variation of the whole system's
      parameters due to the force from the user. In this paper, the characteristics of
      pressures from a user are measured, based on which an adaptive controller is
      proposed to deal with this problem, and validated in an experiment in which a
      pseudo handicapped person follows the ODW. The experimental results show that the
      proposed method can control the ODW to accurately follow the defined path with or
      without a user. 

PMID- 24109837
TI  - Detectability and appraisal thresholds of split pulse signals for the MemoPatchTM
      device, an electronic skin patch intended to deliver tactile medication reminder
      signals (study TS-104).
AB  - Patient non-adherence to prescribed medication regimens is a significant problem
      and affects clinical treatment outcomes. The MemoPatchTM medical device,
      currently in development, is an electronic skin patch intended to deliver tactile
      medication reminder signals. Fifty volunteers completed a laboratory experiment
      that evaluated the detectability and appraisal thresholds of five split signals;
      specifically, the current thresholds (in mA) at which a signal was detected
      (threshold T1), was considered sufficiently detectable to serve as a reminder
      signal (threshold T2), and became too strong as a reminder signal (threshold T3).
      Signals were selected under consideration of three data points: T1Max and T2Max
      (defined as, resp., the maximum current observed at T1 and T2) and T3Pct90 (the
      T3 current at the 90(th) percentile). A signal was considered to be useable in
      future versions of the MemoPatchTM device if it met the constraint that (T3Pct90
      T2Max) should not be negative. One signal met the constraint requirement as its
      T3Pct90-T2Max=0.96mA. 

PMID- 24109838
TI  - Analysis of liquid reservoir effect induced by pulsed laser liquid jet.
AB  - A pulsed-laser-induced liquid jet (LILJ) is a new device used in neurosurgery to
      simultaneously crush, incise, and aspirate tissues and tumors, preserving blood
      vessels and nerves. In addition, a feature of a pulsed LILJ is its ability to
      excavate tissue at constant depth while a liquid jet is being repeatedly focused
      at the same point. To clarify the mechanisms of constant depth of excavation, we
      employed a gelatin phantom and extracted brain tissue using a high-speed camera,
      and we then confirmed that the liquid-reservoir-induced LILJ played an important
      role in enabling the safe usage of an LILJ. 

PMID- 24109839
TI  - A queueing theory based model for business continuity in hospitals.
AB  - Clinical activities can be seen as results of precise and defined events'
      succession where every single phase is characterized by a waiting time which
      includes working duration and possible delay. Technology makes part of this
      process. For a proper business continuity management, planning the minimum number
      of devices according to the working load only is not enough. A risk analysis on
      the whole process should be carried out in order to define which interventions
      and extra purchase have to be made. Markov models and reliability engineering
      approaches can be used for evaluating the possible interventions and to protect
      the whole system from technology failures. The following paper reports a case
      study on the application of the proposed integrated model, including risk
      analysis approach and queuing theory model, for defining the proper number of
      device which are essential to guarantee medical activity and comply the business
      continuity management requirements in hospitals.

PMID- 24109840
TI  - Validation of cleaning evaluation of surgical instruments with RFID tags attached
      based on cleaning appraisal judgment guidelines.
AB  - In medical institutions, the threat of infection is closely focused, in
      particular, inspections regarding surgical site infections (SSI) are carried out.
      In this study, development of the application of Radio frequency identification
      (RFID) tags for surgical instrument has been promoted. It enables traceability
      and individual management of surgical instruments. An experiment was carried out
      following the cleaning Appraisal guidelines, which contaminated surgical
      instruments, and using the washer-disinfector (WD) as the main cleaner for
      surgical instruments with developed RFID tags attached to them. As a result, all
      of the instruments with RFID tags, the amount of residual protein was less than
      the recommended acceptable level of 100ug. If WD is used correctly, a sufficient
      cleaning effect can be expected. From this result, it became evident that the
      secondary infection risk is low from surgical instrument with RFID tags attached.

PMID- 24109841
TI  - Accuracy evaluation of dynamic volume measurements performed by opto-electronic
      plethysmograph, by using a pulmonary simulator.
AB  - Opto-electronic systems (OS) are motion analysis systems, employed in different
      clinical applications. Optoelectronic plethysmograph (OEP) is a particular OS
      able to measure pulmonary volumes, starting from marker displacements, placed on
      the thorax. The aim of this work is to assess the OED's accuracy on volume
      measurements, by using a volumetric respiratory simulator (RS). The RS is
      realized in order to simulate the human quiet breathing and an algorithm computes
      volume variations. Different trials have been carried out, by measuring volume
      through OEP and comparing with volume computed by algorithm. Results show OEP
      accuracy on tidal volume measurement does not depend on thorax displacement's
      magnitude and it ranges from 9% to 20%. Therefore, accuracy of OEP on dynamic
      volume measurements appears not to be influenced by thorax's movement magnitude.

PMID- 24109842
TI  - Performances of heated humidifiers in mechanical ventilation: a preliminary intra
      breath analysis.
AB  - A correct humidification of gases delivered to mechanically ventilated patients
      is essential to avoid some complications. Heated Humidifiers (HHs) are widely
      used in long lasting ventilation to treat gases delivered to patients. Their
      performances depend on some parameters, such as environmental conditions and
      ventilatory settings. The aim of this work is to experimentally assess the
      influence of minute volume (MV), respiratory frequency (f) and the ratio between
      duration of inspiration and expiration (I:E) on HHs performances in terms of
      relative humidity (RH) at the humidification chamber outlet. The main novelty of
      this work is the assessment of RH oscillations during artificial ventilation.
      Results show marked oscillations of RH during a single breath (ripple of 20% in
      the worst case); oscillations decrease if f and I:E increase, on the other hand
      they increase with MV. Since the variation of gas temperature during a
      respiratory act can be neglected, the RH oscillations are related to the vapour
      content in the delivered gases. These results further support the hypothesis
      which asserts that HHs performances could be improved by using a control strategy
      taking into account ventilatory settings.

PMID- 24109843
TI  - Development and evaluation of hardware for Point-of-Care assessment of upper-limb
      motor performance.
AB  - This paper presents prototypes of a hardware interface that is directed towards
      possible integration with a Point-of-Care Testing Environment for Neurological
      Assessment (POCTENA). While the complete system is intended to assist with
      diagnosis of mild Traumatic Brain Injury (TBI), the focus of this paper is to
      present designs of necessary hardware that can be used to assess upper-limb motor
      performance in a point-of-care setting. The hardware interface is expected to
      facilitate execution of several visuomotor tasks in an attempt to reliably
      quantify motor deficits. System usability results are shown to corroborate future
      directions of the POCTENA system. 

PMID- 24109844
TI  - Preliminary results of ON/OFF detection using an integrated system for
      Parkinson's disease monitoring.
AB  - This paper describes the experimental set up of a system composed by a set of
      wearable sensors devices for the recording of the motion signals and software
      algorithms for the signal analysis. This system is able to automatically detect
      and assess the severity of bradykinesia, tremor, dyskinesia and akinesia motor
      symptoms. Based on the assessment of the akinesia, the ON-OFF status of the
      patient is determined for each moment. The assessment performed through the
      automatic evaluation of the akinesia is compared with the status reported by the
      patients in their diaries. Preliminary results with a total recording period of
      32 hours with two PD patients are presented, where a good correspondence (88.2 +/
      3.7 %) was observed. Best (93.7%) and worst (87%) correlation results are
      illustrated, together with the analysis of the automatic assessment of the
      akinesia symptom leading to the status determination. The results obtained are
      promising, and if confirmed with further data, this automatic assessment of PD
      motor symptoms will lead to a better adjustment of medication dosages and timing,
      cost savings and an improved quality of life of the patients. 

PMID- 24109845
TI  - Computerized Lenke classification of scoliotic spine.
AB  - A computer-aided approach was proposed to reduce the variability in the Lenke
      classification. At the first step, endplate inclination of each vertebra on both
      the coronal and sagittal radiographs was measured by a computerized system. The
      Cobb angles of the proximal thoracic, the main thoracic, and the
      thoracolumbar/lumbar curves were then automatically calculated in the standing
      and side-bending coronal planes and the standing sagittal plane. A computerized
      algorithm automatically classified the spinal type. The classification results of
      37 scoliotic patients by five observers showed that with the computer aid, the
      average interobserver and intraobserver kappa values were improved from 0.77 to
      0.88 and from 0.68 to 0.83, respectively. This computerized tool can assist in
      the Lenke classification of scoliosis. 

PMID- 24109846
TI  - In-home measurement of the effect of strategically weighted vests on ambulation.
AB  - Strategically weighted vests are currently being used to treat patients with
      Parkinson's, Multiple Sclerosis, and ataxia. While studies have been conducted to
      demonstrate the effectiveness of these vests, there has been very little research
      into the mechanisms that give rise to the vest's results. This study demonstrates
      the ability to capture gait parameters from depth images[1] in the home with
      sufficient sensitivity to support future investigation of the weighted vest
      intervention. The study also explores multiple metrics, using in-home gait
      sensing, to study a subject's ambulatory ability including gait mechanics,
      uncertainty in motion, and gait cadence. We then investigate the effects of these
      vests on a subject's ambulation by examining these metrics both before and after
      the vest is worn. While only four subjects were used, results are promising,
      showing a statistically significant and clinically significant change in many of
      these metrics as a result of the vest. The cases presented here concern two
      subjects, one with a "tight" gait caused by Progressive Supranuclear Palsy, and
      the second with an excessively "loose" gait due to Parkinson's disease. We show
      that in both subjects, using the vest immediately moved the metrics in a
      direction beneficial to the subject's clinical condition. This result concurs
      with clinical observations as measured using various clinical fall risk
      instruments. 

PMID- 24109847
TI  - Unsupervised segmentation of heel-strike IMU data using rapid cluster estimation
      of wavelet features.
AB  - When undertaking gait-analysis, one of the most important factors to consider is
      heel-strike (HS). Signals from a waist worn Inertial Measurement Unit (IMU)
      provides sufficient accelerometric and gyroscopic information for estimating gait
      parameter and identifying HS events. In this paper we propose a novel adaptive,
      unsupervised, and parameter-free identification method for detection of HS events
      during gait episodes. Our proposed method allows the device to learn and adapt to
      the profile of the user without the need of supervision. The algorithm is
      completely parameter-free and requires no prior fine tuning. Autocorrelation
      features (ACF) of both antero-posterior acceleration (aAP) and medio-lateral
      acceleration (aML) are used to determine cadence episodes. The Discrete Wavelet
      Transform (DWT) features of signal peaks during cadence are extracted and
      clustered using Swarm Rapid Centroid Estimation (Swarm RCE). Left HS (LHS), Right
      HS (RHS), and movement artifacts are clustered based on intra-cluster
      correlation. Initial pilot testing of the system on 8 subjects show promising
      results up to 84.3%+/-9.2% and 86.7%+/-6.9% average accuracy with 86.8%+/-9.2%
      and 88.9%+/-7.1% average precision for the segmentation of LHS and RHS
      respectively. 

PMID- 24109848
TI  - A pilot study on the use of accelerometer sensors for monitoring post acute
      stroke patients.
AB  - The high incidence of stroke has raised a major concern among health
      professionals in recent years. Concerted efforts from medical and engineering
      communities are being exercised to tackle the problem at its early stage. In this
      direction, a pilot study to analyze and detect the affected arm of the stroke
      patient based on hand movements is presented. The premise is that the correlation
      of magnitude of the activities of the two arms vary significantly for stroke
      patients from controls. Further, the cross-correlation of right and left arms for
      three axes are differentiable for patients and controls. A total of 22 subjects
      (15 patients and 7 controls) were included in this study. An overall accuracy of
      95.45% was obtained with sensitivity of 1 and specificity of 0.86 using
      correlation based method. 

PMID- 24109849
TI  - Monitoring technology for wheelchair users with advanced multiple sclerosis.
AB  - This paper presents a non-invasive assistive device for people with advanced
      Multiple Sclerosis (MS) who use electric power wheelchairs (EPW). The proposed
      system can acquire respiration and heart activity from ballistocardiogram (BCG),
      seat and back pressure distribution, wheelchair tilt angle and ambient
      temperature and relative humidity. The sensors collect information related to the
      main issues of MS patients: fatigue, heat sensitivity and low mobility.
      Preliminary results show the signals as the wheelchair is moving, stopped and
      tilting. The system is able to capture sufficient relevant information to provide
      suggestions and alarms in a future stage. The system will be tested at The Boston
      Home, a specialized residence for adults with advanced MS. 

PMID- 24109850
TI  - Application of a variation of empirical mode decomposition and Teager energy
      operator to EEG signals for mental task classification.
AB  - This paper presents a simple and effective methodology for mental task
      classification using a novel variation of the empirical mode decomposition (EMD)
      algorithm and the Teager energy operator applied to electroencephalography (EEG)
      signals. EEG signals corresponding to various types of mental tasks performed by
      human subjects are decomposed using the variation of EMD, called Empirical Mode
      Decomposition-Modified Peak Selection (EMD-MPS), which allows direct separation
      of the signals into a de-trended component, and a trend, according to a frequency
      separation criterion. Teager energy operator is then applied to calculate the
      average energy values of both components obtained after signal decomposition
      using EMD-MPS. These energy values are used to construct feature vectors, and one
      versus-one classification of mental tasks is performed using a simple classifier,
      namely the 1-NN classifier. An average correct classification rate of 87% is
      obtained, improving on previous results and thereby also demonstrating the
      effectiveness of the methodology. 

PMID- 24109851
TI  - Adaptive neuro-fuzzy inference system for acoustic analysis of 4-channel
      phonocardiograms using empirical mode decomposition.
AB  - The heart's mechanical activity can be appraised by auscultation recordings,
      taken from the 4-Standard Auscultation Areas (4-SAA), one for each cardiac valve,
      as there are invisible murmurs when a single area is examined. This paper
      presents an effective approach for cardiac murmur detection based on adaptive
      neuro-fuzzy inference systems (ANFIS) over acoustic representations derived from
      Empirical Mode Decomposition (EMD) and Hilbert-Huang Transform (HHT) of 4-channel
      phonocardiograms (4-PCG). The 4-PCG database belongs to the National University
      of Colombia. Mel-Frequency Cepstral Coefficients (MFCC) and statistical moments
      of HHT were estimated on the combination of different intrinsic mode functions
      (IMFs). A fuzzy-rough feature selection (FRFS) was applied in order to reduce
      complexity. An ANFIS network was implemented on the feature space, randomly
      initialized, adjusted using heuristic rules and trained using a hybrid learning
      algorithm made up by least squares and gradient descent. Global classification
      for 4-SAA was around 98.9% with satisfactory sensitivity and specificity, using a
      50-fold cross-validation procedure (70/30 split). The representation capability
      of the EMD technique applied to 4-PCG and the neuro-fuzzy inference of acoustic
      features offered a high performance to detect cardiac murmurs. 

PMID- 24109852
TI  - Detection of phase synchronization in EEG with Bivariate Empirical Mode
      Decomposition.
AB  - In recent years, the phase synchronization phenomenon in the
      electroencephalograph (EEG) has been widely used to observe interactions between
      separate areas of the cortex. However, the traditional coherence to measure the
      phase synchronization need target signals to be stationary. In this paper, we
      propose a technique to measure the phase synchrony of non-stationary signals by
      the Phase Locking Value (PLV) with Hilbert transform and the Bivariate Empirical
      Mode Decomposition (BEMD). We analyzed the phase synchronization of EEG signals
      which were recorded during Dynamical Dot Quartet (DDQ) tasks using the
      conventional method and the proposed method. The analysis result suggests that
      proposed method more suitable for detecting the phase synchrony during the DDQ
      tasks than the conventional methods. 

PMID- 24109853
TI  - Employing ensemble empirical mode decomposition for artifact removal: extracting
      accurate respiration rates from ECG data during ambulatory activity.
AB  - Observation of a patient's respiration signal can provide a clinician with the
      required information necessary to analyse a subject's wellbeing. Due to an
      increase in population number and the aging population demographic there is an
      increasing stress being placed on current healthcare systems. There is therefore
      a requirement for more of the rudimentary patient testing to be performed outside
      of the hospital environment. However due to the ambulatory nature of these
      recordings there is also a desire for a reduction in the number of sensors
      required to perform the required recording in order to be unobtrusive to the
      wearer, and also to use textile based systems for comfort. The extraction of a
      proxy for the respiration signal from a recorded electrocardiogram (ECG) signal
      has therefore received considerable interest from previous researchers. To allow
      for accurate measurements, currently employed methods rely on the availability of
      a clean artifact free ECG signal from which to extract the desired respiration
      signal. However, ambulatory recordings, made outside of the hospital-centric
      environment, are often corrupted with contaminating artifacts, the most degrading
      of which are due to subject motion. This paper presents the use of the ensemble
      empirical mode decomposition (EEMD) algorithm to aid in the extraction of the
      desired respiration signal. Two separate techniques are examined; 1) Extraction
      of the respiration signal directly from the noisy ECG 2) Removal of the artifact
      components relating to the subject movement allowing for the use of currently
      available respiration signal detection techniques. Results presented illustrate
      that the two proposed techniques provide significant improvements in the accuracy
      of the breaths per minute (BPM) metric when compared to the available true
      respiration signal. The error reduced from +/- 5.9 BPM prior to the use of the
      two techniques to +/- 2.9 and +/- 3.3 BPM post processing using the EEMD
      algorithm techniques. 

PMID- 24109854
TI  - Estimation of instantaneous frequency from empirical mode decomposition on
      respiratory sounds analysis.
AB  - Instantaneous frequency (IF) calculated by empirical mode decomposition (EMD)
      provides a novel approach to analyze respiratory sounds (RS). Traditionally, RS
      have been analyzed using classical time-frequency distributions, such as short
      time Fourier transform (STFT) or wavelet transform (WT). However, EMD has become
      a powerful tool for nonlinear and non-stationary data analysis. IF estimated by
      EMD has two major advantages: its high temporal resolution and the fact that a
      priori knowledge of the signal characteristics is not required. In this study, we
      have estimated IF by EMD on real RS signals in order to identify continuous
      adventitious sounds (CAS), such as wheezes, within inspiratory sounds cycles. We
      show that there are differences in IF distribution among frequency scales of RS
      signal when CAS are within RS. Therefore, a new method for RS analysis and
      classification may be developed by combining both EMD and IF. 

PMID- 24109855
TI  - Low frequency-modulated high frequency oscillations in seizure-like events
      recorded from in-vivo MeCP2-deficient mice.
AB  - Rett syndrome is a neurodevelopmental condition caused by mutations in the gene
      encoding methyl CpG-binding protein 2 (MeCP2). Seizures are often associated with
      Rett syndrome and can be observed in intracranial electroencephalogram (iEEG)
      recordings. To date most studies have focused on the low frequencies oscillations
      (LFOs), however recent findings in epilepsy studies link high frequency
      oscillations (HFOs) with epileptogenesis. In this study, we examine the presence
      of HFOs in the male and female MeCP2-deficient mouse models of Rett syndrome and
      their interaction with the LFOs present during seizure-like events (SLEs). Our
      findings indicate that HFOs (200-600 Hz) are present during the SLEs and in
      addition, we reveal strong phase-amplitude coupling between LFOs (6-10 Hz) and
      HFOs (200-600 Hz) during female SLEs in the MeCP2-deficient mouse model. 

PMID- 24109856
TI  - Classification of wheelchair commands using brain computer interface: comparison
      between able-bodied persons and patients with tetraplegia.
AB  - This paper presents a three-class mental task classification for an
      electroencephalography based brain computer interface. Experiments were conducted
      with patients with tetraplegia and able bodied controls. In addition, comparisons
      with different time-windows of data were examined to find the time window with
      the highest classification accuracy. The three mental tasks used were letter
      composing, arithmetic and imagery of a Rubik's cube rolling forward; these tasks
      were associated with three wheelchair commands: left, right and forward,
      respectively. An eyes closed task was also recorded for the algorithms testing
      and used as an additional on/off command. The features extraction method was
      based on the spectrum from a Hilbert-Huang transform and the classification
      algorithm was based on an artificial neural network with a fuzzy particle swarm
      optimization with cross-mutated operation. The results show a strong eyes closed
      detection for both groups with average accuracy at above 90%. The overall result
      for the combined groups shows an improved average accuracy of 70.6% at 1s, 74.8%
      at 2s, 77.8% at 3s, 79.6% at 4s and 81.4% at 5s. The accuracy for individual
      groups were lower for patients with tetraplegia compared to the able-bodied
      group, however, does improve with increased duration of the time-window. 

PMID- 24109857
TI  - Optimal sampling frequency in wavelet-based signal feature extraction using
      particle swarm optimization.
AB  - A methodology for optimum sampling frequency selection for wavelet feature
      extraction is presented. We show that classification accuracy is enhanced by
      adequately selecting the parameters: number of decomposition levels, wavelet
      function and sampling rate. A novel approach for selecting the parameters based
      on particle swarm optimization (PSO) is presented. Experimental results conducted
      on two different datasets with support vector machine (SVM) classifiers confirm
      the superiority and advantages of the proposed method. It is shown empirically
      that the proposed method outperforms significantly the existing methods in terms
      of accuracy rate. 

PMID- 24109858
TI  - Analysis and modeling of noise in biomedical systems.
AB  - Noise characteristics play an important role in evaluating tools developed to
      study biomedical systems. Despite usual assumptions, noise in biomedical systems
      is often nonwhite or non-Gaussian. In this paper, we present a method to analyze
      the noise component of a biomedical system. We demonstrate the effectiveness of
      the method in the analysis of noise in voluntary ankle torque measured by a
      torque transducer and eye movements measured by electro-oculography (EOG). 

PMID- 24109859
TI  - Exercise muscle fatigue detection system implementation via wireless surface
      electromyography and empirical mode decomposition.
AB  - Surface electromyography (sEMG) is an important measurement for monitoring
      exercise and fitness. A wireless Bluetooth transmission sEMG measurement system
      with a sampling frequency of 2 KHz is developed. Traditional muscle fatigue is
      detected from the median frequency of the sEMG power spectrum. The regression
      slope of the linear regression of median frequency is an important muscle fatigue
      index. As fatigue increases, the power spectrum of the sEMG shifts toward lower
      frequencies. The goal of this study is to evaluate the sensitivity of empirical
      mode decomposition (EMD) quantifying the electrical manifestations of the local
      muscle fatigue during exercising in health people. We also compared this method
      with the raw data and discrete wavelet transform (DWT). Five male and five female
      volunteers participated. Each subject was asked to run on a multifunctional
      pedaled elliptical trainer for about 30 minutes, twice a week, and there were a
      total of six recording times for each subject with a wireless EMG recording
      system. The results show that sensitivity of the highest frequency component of
      EMD is better than the highest frequency component of DWT, and raw data. 

PMID- 24109860
TI  - Seizure detection methods using a cascade architecture for real-time implantable
      devices.
AB  - Implantable high-accuracy, and low-power seizure detection is a challenge. In
      this paper, we propose a cascade architecture to combine different seizure
      detection algorithms to optimize power and accuracy of the overall seizure
      detection system. The proposed architecture consists of a cascade of two seizure
      detection stages. In the first-stage detector, a lightweight (low-power)
      algorithm is used to detect seizure candidates with the understanding that there
      will be a high number of false positives. In the second-stage detector-and only
      for the seizure candidates detected in the first detector-a high-accuracy
      algorithm is used to eliminate the false positives. We show that the proposed
      cascade architecture can reduce power consumption of seizure detection by 80%
      with high accuracy, offering a suitable option for real-time implantable seizure
      detectors. 

PMID- 24109861
TI  - Compression-ratio-based seizure detection.
AB  - For wireless seizure monitoring devices seizure detection and data compression
      are two critical tasks that need to be carefully designed against a very tight
      power budget to maximize the battery life. These two tasks are usually considered
      separately and algorithms for each are developed separately. In this paper, we
      consider having a single low-power algorithm for implementing both seizure
      detection and data compression. Towards that end, we investigated compression
      ratio (CR) as a seizure marker and show that the seizure detection can be
      achieved as a by-product of compression with no additional cost, and thus overall
      system power can be reduced. We show that the proposed method, the CR-based
      seizure detection has promising performance with 88% seizure detection accuracy,
      and 5.5 false positives per hour (FPh) without any computation overhead. 

PMID- 24109862
TI  - A novel through-wall respiration detection algorithm using UWB radar.
AB  - Through-wall respiration detection using Ultra-wideband (UWB) impulse radar can
      be applied to the post-disaster rescue, e.g., searching living persons trapped in
      ruined buildings after an earthquake. Since strong interference signals always
      exist in the real-life scenarios, such as static clutter, noise, etc., while the
      respiratory signal is very weak, the signal to noise and clutter ratio (SNCR) is
      quite low. Therefore, through-wall respiration detection using UWB impulse radar
      under low SNCR is a challenging work in the research field of searching survivors
      after disaster. In this paper, an improved UWB respiratory signal model is built
      up based on an even power of cosine function for the first time. This model is
      used to reveal the harmonic structure of respiratory signal, based on which a
      novel high-performance respiration detection algorithm is proposed. This novel
      algorithm is assessed by experimental verification and simulation and shows about
      a 1.5dB improvement of SNR and SNCR. 

PMID- 24109863
TI  - Analysis and evaluation of vascular sounds in hemodialysis.
AB  - A vascular access is required for hemodialysis. Because the vascular access is an
      important lifeline for patients with renal failure, its monitoring and management
      are essential. The vascular access is typically monitored through auscultation of
      vascular sounds because these sounds provide some indication of access patency;
      however, this is not a quantitative assessment. The objective of this study is to
      develop a quantitative assessment of vascular sounds in hemodialysis. We propose
      several parameters to evaluate discontinuities in sound power and to specify the
      shape of the power spectrum, using signal processing techniques such as the
      theory of spectral distance with autoregressive model and the nonlinear closing
      operation from the field of mathematical morphology, which is essential for
      robust segmentation of waveform. In our demonstrations, abnormal vascular sounds
      are seen to exhibit different parameters compared to normal sounds. This shows
      that these parameters may be useful for assessing conditions of vascular sounds. 

PMID- 24109864
TI  - Evaluating epicardial mapping electrogram by the method of dominant frequency and
      Lorenz plot.
AB  - The methods of dominant frequency and Lorenz plot are used in this study to
      evaluate the activation rate and the activation rate variability of cardiac
      signals during atrial fibrillation. An epicardial mapping system was applied to
      acquire the atrial electrogram of mongrel dogs. The dominant frequency and Lorenz
      plot of each signal from various myocardial regions of the atria were analyzed.
      Our results show that both a frequency gradient and a variability gradient exist
      in the atria and the roots of pulmonary veins. The dominant frequencies of the
      anterior atria are higher than the posterior ones and the activation variability
      of both atria was higher than those of the pulmonary veins. A combination of
      these two methods may provide a more comprehensive understanding of the
      electrophysiology mechanism associated with atrial fibrillation. 

PMID- 24109865
TI  - Statistical significance of task related deep brain EEG dynamic changes in the
      time-frequency domain.
AB  - We present an off-line analysis procedure for exploring brain activity recorded
      from intra-cerebral electroencephalographic data (SEEG). The objective is to
      determine the statistical differences between different types of stimulations in
      the time-frequency domain. The procedure is based on computing relative signal
      power change and subsequent statistical analysis. An example of characteristic
      statistically significant event-related de/synchronization (ERD/ERS) detected
      across different frequency bands following different oddball stimuli is
      presented. The method is used for off-line functional classification of different
      brain areas. 

PMID- 24109866
TI  - Automated signal pattern detection in ECG during human ventricular arrhythmias.
AB  - Ventricular arrhythmias seriously affects cardiac function. Of these arrhythmias,
      Ventricular fibrillation is considered as a lethal cardiac condition. Recent
      studies have reported that ventricular arrhythmias are not completely random and
      may exhibit regional spatio-temporal organizations. These organizations could be
      indicative of reoccurring signal patterns and might be embedded within the
      surface electrocardiograms (ECGs) during ventricular arrhythmias. In this work,
      we aim to identify such reoccurring ECG signal patterns during ventricular
      arrhythmias. The detection of such signal patterns and their distribution could
      be of help in sub-classifying the affected population for better targeted
      diagnosis and treatment. Our analysis on 14 ECG segments (on average 3.24 minutes
      per segment) obtained from the MIT-BIH ventricular arrhythmia database identified
      three reoccurring signal patterns. A wavelet based technique was developed for
      automating the pattern identification process using ECGs. The proposed method
      achieved automated detection accuracies of 73.3%, 75.0% and 86.6% for the
      proposed signal patterns. 

PMID- 24109867
TI  - Electrooculogram filtering using wavelet and wavelet packet transforms.
AB  - This paper presents a proposal for filtering electrooculogram signals using the
      Discrete Wavelet and the Discrete Wavelet Packet Transforms. We compare our
      proposal with other digital filters commonly used for this type of biological
      signals, evaluating the results in terms of signal-to-noise ratio improvement,
      energy, correlation coefficient and mean absolute error reduction. For the
      analyzed cases, the wavelet and wavelet packet approaches improve considerably
      the results obtained with digital filters. Moreover, we also provide the most
      suitable parameters for the wavelet and the wavelet packet analysis. 

PMID- 24109868
TI  - Influence of ionotropic receptors localization on glutamatergic synaptic response
      to paired-pulse stimulation protocol.
AB  - Paired-pulse protocol is a stimulation pattern that is often used to characterize
      short-term changes in synaptic potency. Responses to such protocol often yield
      varying results, going from a depressing response to a facilitated one following
      the second pulse. Similarly, experimental results have shown that synaptic
      structures are dynamic and receptors move along the postsynaptic membrane. The
      present study provides insights on the impact of glutamatergic receptors
      localization with respect to the neurotransmitters release site on the
      postsynaptic currents measured; it also proposes an explanation on the diversity
      of responses observed experimentally. The platform we used is the EONS/RHENOMS
      modeling platform widely described in the literature, which encompasses a
      multitude of highly detailed subsynaptic elements to most faithfully replicate
      synaptic function. 

PMID- 24109869
TI  - Insights on synaptic paired-pulse response using parametric and non-parametric
      models.
AB  - Paired-pulse protocol is a well-established stimulation pattern used to
      characterize short-term changes in synaptic potency. Due to the experimental
      difficulty in accessing and measuring responses and interactions between
      subsynaptic elements, understanding the mechanisms that shape synaptic response
      is extremely challenging. We already proposed to address this issue and gain
      insights on the matter using a complex integrated modeling platform called EONS
      (Elementary Objects of the Nervous System). The use of this parametric platform
      provided us with insightful information on the subsynaptic components and how
      their interactions shape synaptic dynamics. We herein propose to add and combine
      a non-parametric model to (i) simplify the modeling framework, the number of
      underlying parameters and the overall computational complexity while faithfully
      maintaining the desirable synaptic behavior and (ii) provide a clear and concise
      framework to characterize AMPA and NMDA contributions to the observed paired
      pulse responses. 

PMID- 24109870
TI  - Analysis of neuronal cells of dissociated primary culture on high-density CMOS
      electrode array.
AB  - Spontaneous development of neuronal cells was recorded around 4-34 days in vitro
      (DIV) with high-density CMOS array, which enables detailed study of the spatio
      temporal activity of neuronal culture. We used the CMOS array to characterize the
      evolution of the inter-spike interval (ISI) distribution from putative single
      neurons, and estimate the network structure based on transfer entropy analysis,
      where each node corresponds to a single neuron. We observed that the ISI
      distributions gradually obeyed the power law with maturation of the network. The
      amount of information transferred between neurons increased at the early stage of
      development, but decreased as the network matured. These results suggest that
      both ISI and transfer entropy were very useful for characterizing the dynamic
      development of cultured neural cells over a few weeks. 

PMID- 24109871
TI  - Effective digitized spatial size of unit dipole field in Quantitative
      Susceptibility Mapping.
AB  - Quantitative Susceptibility Mapping (QSM) calculates a distribution of tissue
      magnetic susceptibility difference in vivo using measured magnetic field
      perturbation. The magnetic field perturbation can be approximated in first order
      by convolution of the susceptibility distribution with a spatial unit dipole
      field. Since the convolution has to be done in all space, a novel technique using
      harmonic properties of the dipole field is introduced to confine the calculation
      within the measurable region. However, discretized dipole field does not satisfy
      the harmonic property near its orign. Here, we investigate an effective spatial
      size of the dipole field in relation with the nonharmonic property using Shepp
      Logan phantoms including partial volume effects. This study suggests that the
      dipole field can be effectively restricted to 15 voxels in diameter and that this
      value relates with the nonharmonic region of the discretized dipole field.
      Moreover, the effective size in a real space is scaled with a spatial resolution
      of a QSM experiment. 

PMID- 24109872
TI  - Unsupervised segmentation of brain regions with similar microstructural
      properties: application to alcoholism.
AB  - In this work, a novel brain MRI segmentation approach evaluates microstructural
      differences between groups. Going further from the traditional segmentation of
      brain tissues (white matter -WM-, gray matter -GM- and cerebrospinal fluid -CSF-
      or a mixture of them), a new way to classify brain areas is proposed using their
      microstructural MR properties. Eight rats were studied using the proposed
      methodology identifying regions which present microstructural differences as a
      consequence on one month of hard alcohol consumption. Differences in relaxation
      times of the tissues have been found in different brain regions (p<0.05).
      Furthermore, these changes allowed the automatic classification of the animals
      based on their drinking history (hit rate of 93.75 % of the cases). 

PMID- 24109873
TI  - Classification of bipolar disorder using basal-ganglia-related functional
      connectivity in the resting state.
AB  - The emotional and cognitive symptoms of bipolar disorder (BD) are suggested to
      involve in a distributed neural network. The resting-state functional magnetic
      resonance imaging (fMRI) offers an important tool to investigate the alterations
      in brain network level of BD. The aim of this study was to discriminate BD
      patients from healthy controls using whole-brain resting-state functional
      connectivity patterns. The majority of most discriminating functional
      connectivities were between the basal ganglia and three core neurocognitive
      networks, including the default mode, executive control and salience networks.
      Using these resting-state functional connectivities between the basal ganglia and
      three core neurocognitive networks as the features, the clustering accuracy
      achieved 90%. 

PMID- 24109874
TI  - Bloch simulations towards direct detection of oscillating magnetic fields using
      MRI with spin-lock sequence.
AB  - A new MRI method using the spin-lock sequence has attracted wide attention
      because of its potential for detecting small oscillating magnetic fields.
      However, as the mechanism involved is complicated, we visualized the
      magnetization performance during the spin-lock sequence in order to better
      understand interaction of the spin-lock pulse and the externally applied
      oscillating magnetic fields by means of a fast-and-simple method using matrix
      operations to solve a time-dependent Bloch equation. To improve spin-lock imaging
      in the detection of small magnetic fields (in an fMRI experiment that modeled
      neural magnetic fields), we observed that the phenomenon decreases MR signals,
      which led us to investigate how spin-lock parameters cause the MR signal to
      decrease; based on this, we determined that MR signals decrease in oscillating
      magnetic fields that are resonant with the spin-lock pulse. We also determined
      that MR signals decrease is directly proportional to spin-lock duration. Our
      results suggest that MRI can feasibly detect oscillating magnetic fields directly
      by using of the spin-lock sequence. 

PMID- 24109875
TI  - A phantom and in vivo study of mice following an ischemic stroke using sodium
      MRI.
AB  - Sodium is one of the essential indicators of cell viability in vivo. Regarding
      extant literature, sodium MRI is widely employed for various studies, including
      research on tumors, strokes, and neurocognition, because it can non-invasively
      provide data of physiological metabolism in vivo. Currently, strokes are among
      the 3 leading causes of death worldwide, and can be categorized as hemorrhagic or
      ischemic. Approximately 70% to 80% of stroke patients experience an ischemic
      stroke. Although numerous relevant studies have focused on larger animal models,
      such as rats, cats, and nonhuman primates, literature that employs mice
      experimental models is scarce. In this study, we conducted sodium MRI on the
      brains of mice after an ischemic stroke to observe sodium signal variations in
      the brain following this type of stroke. The findings indicated that the sodium
      signals in the brain regions affected by stroke were 2.3 times stronger than
      those in the lateral ventricles. 

PMID- 24109876
TI  - Neurophysiological correlates of different moods and feelings induced by chords
      and harmonized scales revealed by fMRI.
AB  - Activated brain areas in response to major, minor, augmented and diminished
      chords as well as to major and minor harmonized scales were investigated by fMRI.
      The activated areas for the chord experiments included regions related to emotion
      processing. Results of the scale experimnts were less straightforward than those
      of the chord experiments. Possible relationship between the known functions of
      the areas activated by each category of stimuli and the behavioral (emotinal)
      effects of the category was discussed. 

PMID- 24109877
TI  - Theoretical study of evaluation method for MRI metal artifact.
AB  - In dental field, the effect of the Magnetic Resonance Imaging (MRI) artifact
      generated by the magnetic metal is a significant problem. The MRI metal artifact
      occurs when using magnetic attachment and the keeper of the ferromagnetic
      substance remains implanted in the mouth as the MR image is taken. In this study,
      we theoretically evaluated and analyzed the artifact of MR images caused by the
      keeper based on the actual principle of MRI by means of simulation. As a result
      we were able to recognize the changes and distortion in the signal strength of
      the output image. We found that our results of output images and previously
      reported results of actual measurement are very similar. MRI artifact caused by
      dental magnetic metal showed that it can be reported by theoretical simulation. 

PMID- 24109878
TI  - Superpixels in brain MR image analysis.
AB  - A large number of sophisticated techniques have been proposed over the last few
      decades for automatic analysis of brain MR images to help clinicians better
      diagnose and understand anatomical changes due to neurological disorders. While
      significant improvements in performance have been achieved, almost all techniques
      suffer from a common limitation of high computational complexity due to the large
      number of voxels present in a typical MR volume. Computational complexity is a
      major hurdle in the clinical application of these sophisticated image analysis
      techniques. Brain MR volumes consist of approximately piecewise constant tissue
      regions with high redundancy among voxel intensities, which can be grouped into
      perceptually meaningful entities (superpixels) to reduce the complexity. In this
      study, we investigate the utility of superpixels (2D) and supervoxels (3D) in
      reducing computational complexity of brain MR analysis tasks. We investigate the
      extent of spatial and intensity distortions introduced in superpixel
      representation of MR images and evaluate its effect on brain tissue segmentation
      as an example task. We observe that superpixels are highly promising for
      significantly reducing the computational complexity of the lower-level image
      analysis tasks that are often essential components of MR analysis pipelines. 

PMID- 24109879
TI  - On high-resolution image estimation using low-resolution brain MRI.
AB  - In the context of medical imaging, super-resolution (SR) is currently a promising
      post-processing technique to increase the image resolution. However, although
      many SR methods have been proposed in the literature, the gain of this type of
      approach in a real situation has not been precisely quantified. In this work, we
      evaluate image acquisition protocols and SR algorithms using in-vivo brain MR
      data as gold standard. The results show that using orthogonal image acquisition
      protocols lead to better reconstructed images than overlapping parallel low
      resolution image stacks. Moreover, if the preprocessing steps (such as image
      denoising and intensity correction) are carefully performed, there is no
      significant differences between the evaluated SR algorithms. 

PMID- 24109880
TI  - Mitigate B1(+) inhomogeneity by nonlinear gradients and RF shimming.
AB  - High-field MRI has the challenge of inhomogeneous B1(+) and consequently an
      inhomogeneous flip angle distribution. This causes spatially dependent contrast
      and makes clinical diagnosis difficult. Under the small flip angle approximation
      and using nonlinear spatial encoding magnetic fields (SEMs), we propose a method
      to remap the B1(+) map into a lower dimension coordinate system. Combining with
      RF shimming method, a simple pulse sequence design using nonlinear SEMs can
      achieve a homogenous flip angle distribution efficiently. Using simulations, we
      demonstrate that combining RF shimming and spatially selective RF excitation
      using generalized SEMs (SAGS) using linear and quadratic SEMs in a multi-spoke k
      space trajectory can mitigate the B1(+) inhomogeneity at 7T efficiently without
      using parallel RF transmission. 

PMID- 24109881
TI  - A fast pulse design for parallel excitation with gridding conjugate gradient.
AB  - Parallel excitation (pTx) is recognized as a crucial technique in high field MRI
      to address the transmit field inhomogeneity problem. However, it can be time
      consuming to design pTx pulses which is not desirable. In this work, we propose a
      pulse design with gridding conjugate gradient (CG) based on the small-tip-angle
      approximation. The two major time consuming matrix-vector multiplications are
      substituted by two operators which involves with FFT and gridding only.
      Simulation results have shown that the proposed method is 3 times faster than
      conventional method and the memory cost is reduced by 1000 times. 

PMID- 24109882
TI  - Synthesis and proton NMR spectroscopy of intra-vesicular gamma-aminobutyric acid
      (GABA).
AB  - We report the synthesis of vesicles containing gamma-aminobutyric acid (GABA),
      and their proton nuclear magnetic resonance ((1)H NMR) spectra. These vesicles
      were constructed to more closely mimic the intracellular environment wherein GABA
      exists. For this study, these GABA-containing vesicles were examined under (1)H
      NMR as a potential platform for future studies on the differences between aqueous
      phantoms, ex vivo brain extracts, and in vivo magnetic resonance spectroscopy
      results. We found that intra-vesicular GABA faithfully yielded the chemical
      shifts and J-coupling constants of free aqueous GABA, alongside the chemical
      shift signals of the vesicle wall. 

PMID- 24109883
TI  - Nonlinear coil sensitivity estimation for parallel magnetic resonance imaging
      using data-adaptive steering kernel regression method.
AB  - The parallel magnetic resonance imaging (parallel imaging) technique reduces the
      MR data acquisition time by using multiple receiver coils. Coil sensitivity
      estimation is critical for the performance of parallel imaging reconstruction.
      Currently, most coil sensitivity estimation methods are based on linear
      interpolation techniques. Such methods may result in Gibbs-ringing artifact or
      resolution loss, when the resolution of coil sensitivity data is limited. To
      solve the problem, we proposed a nonlinear coil sensitivity estimation method
      based on steering kernel regression, which performs a local gradient guided
      interpolation to the coil sensitivity. The in vivo experimental results
      demonstrate that this method can effectively suppress Gibbs ringing artifact in
      coil sensitivity and reduces both noise and residual aliasing artifact level in
      SENSE reconstruction. 

PMID- 24109884
TI  - Assessment of flow and hemodynamics in the carotid artery using a reduced TE 4D
      flow spiral phase-contrast MRI.
AB  - 4D flow MRI is a powerful technique for quantitative flow assessment and
      visualization of complex flow patterns and hemodynamics of cardiovascular flows.
      This technique results in more anatomical information and comprehensive
      assessment of blood flow. However, conventional 4D PC MRI suffers from a few
      obstacles for clinical applications. The total scan time is long, especially in
      large volumes with high spatial resolutions. Inaccuracy of conventional Cartesian
      PC MRI in the setting of atherosclerosis and in general, disturbed and turbulent
      blood flow is another important challenge. This inaccuracy is the consequence of
      signal loss, intravoxel dephasing and flow-related artifact in the presence of
      disturbed and turbulent flow. Spiral k-space trajectory has valuable attributes
      which can help overcome some of the problems with 4D flow Cartesian acquisitions.
      Spiral trajectory benefits from shorter TE and reduces the flow-related
      artifacts. In addition, short spiral readouts with spiral interleaves can
      significantly reduce the total scan time, reducing the chances of patient motion
      which may also corrupt the data in the form of motion artifacts. In this paper,
      the accuracy of flow assessment and flow visualization with reduced TE 4D Spiral
      PC was investigated and good agreement was observed between the spiral and
      conventional technique. The systolic mean velocity, peak flow and the average
      flow in CCA and ICA of normal volunteers using 4D spiral PC MRI showed errors
      less than 10% compared to conventional 4D PC MRI. In addition, the scan time
      using spiral sequence was 3?31 min which is half of the time using conventional
      sequence. 

PMID- 24109885
TI  - Noise estimation in magnetic resonance SENSE reconstructed data.
AB  - Parallel imaging methods allow to increase the acquisition rate via subsampled
      acquisitions of the k-space. SENSE is one of the most popular reconstruction
      methods proposed in order to suppress the artifacts created by this subsampling.
      However, the SENSE reconstruction process yields to a variance of noise value
      which is dependent on the position within the image. Hence, the traditional noise
      estimation methods based on a single noise level for the whole image fail.
      Accordingly, we propose a novel method to recover the complete spatial pattern of
      the variance of noise in SENSE reconstructed images up from the sensitivity maps
      of each receiver coil. Our method fits applications in statistical image
      processing tasks such as image denoising. 

PMID- 24109886
TI  - Preliminary study of non-invasive shock wave treatment of capsular contracture
      after breast implant: animal model.
AB  - The incidence rate of capsular contracture after breast implant is about 8% to
      12%. Patients would feel extremely uncomfortable after scar formation.
      Administering oral medications (such as vitamin E and Zafirlukast tablets, etc.)
      or invasive breast capsulectomy surgery was commonly used for capsular
      contracture repair in clinical therapy. However, the therapeutic effect is still
      under investigation. Shock waves can be used to remove soft connective tissue in
      clinical applications. It has been widely used in orthopedics and rehabilitation.
      No related research paper about shock wave treatment of capsular contracture has
      been published yet. It might provide another choice for capsular contracture
      repair. In order to simulate breast implantation, two silica-gel bags filled with
      normal saline were implanted into New Zealand rabbit's thighs bilaterally as an
      animal model. Six weeks later, daily shock wave treatment on the right thigh was
      performed for six weeks after capsular contractures were formed, while the other
      thigh was used as a control. Then, magnetic resonance imaging (MRI) was used to
      compare the difference between treated and un-treated thighs. Afterwards,
      pathological sections were analyzed to confirm the findings. It has been
      demonstrated that shock wave treatments are capable of changing the structure and
      composition of capsular contractures. The structure of scar became myxoid changed
      or collagen deposition of scar decreased after shock wave treatment, hence, the
      formation of scars decreased. Increased myxoid and decreased collagen deposition
      has also been found. 

PMID- 24109887
TI  - Relation between morphology of sebaceous glands inside human skin and
      viscoelastic properties.
AB  - Three-dimensional ultrasound microscopy with the central frequency of 120 MHz
      made it possible to observe in vivo sebaceous glands at the deep part of the
      dermis at microscopic level. The deformation displacements were measured by an
      established testing device, and the viscoelasticity was estimated from the
      measured displacements and Voigt model. The occupancy, density or average size of
      sebaceous glands was compared with the viscoleasticity. There were three major
      findings in the comparisons. First, the occupancy of sebaceous gland showed
      negative correlation with the elasticity. Second, the density of sebaceous glands
      showed positive correlation with the viscosity. Third, the average size of
      sebaceous glands showed negative correlation with the viscosity. In conclusion,
      viscoelastic property of human skin is strongly influenced by the morphology of
      the sebaceous glands. 

PMID- 24109888
TI  - Ultrasonic and photoacoustic imaging of knee joints in normal and osteoarthritis
      rats.
AB  - Osteoarthritis (OA) is a common joint disorder and estimated to cause symptoms in
      20-40% of the elderly population. 532 nm laser is much absorbed in developed
      vascular network in the spongy bone which is one of the main characteristics of
      OA. In this study, a photoacoustic (PA) imaging system with 532 nm laser and 50
      MHz US (ultrasound) transducer was developed. Normal and OA knee joints were
      observed by US and PA imaging. PA signal from the spongy bone was strong where US
      reflection was very weak. PA signal from the spongy bone was significantly strong
      in OA compared with that in normal knee while US showed similar low intensity
      echo in normal and OA. Detailed structure and information on vascular density of
      spongy bone in rat knee joint were successfully obtained with US / PA combined
      imaging. US / PA imaging should be useful for early diagnosis of OA. 

PMID- 24109889
TI  - Preliminary study on the effect of stiffness on lamb wave propagation in bovine
      corneas.
AB  - The viscoelastic properties of human cornea could provide valuable information
      for various clinical applications. Particularly, it will be helpful to achieve a
      patient-specific biomechanical optimization in LASIK refractive surgery, early
      detection of corneal ecstatic disease or improved accuracy of intraocular
      pressure (IOP) measurement. However, there are few techniques that are capable of
      accurately assessing the corneal elasticity in situ in a nondestructive fashion.
      In order to develop a quantitative method for assessing both elasticity and
      viscosity of the cornea, we use ultrasound radiation force to excite Lamb waves
      in cornea, and a pulse echo transducer to track the tissue vibration. The fresh
      postmortem bovine eyes were treated via collagen cross-linking to make the cornea
      stiff. The effect of stiffness was studied by comparing the propagation of Lamb
      waves in normal and treated corneas. It was found that the waveform of generated
      Lamb waves changed significantly due to the increase in higher modes in treated
      corneas. This result indicated that the generated waveform was a complex of
      multiple harmonics and the varied stiffness will affect the energy distribution
      over different components. Therefore, it is important for assessing the
      viscoelastic properties of the cornea to know the components of Lamb wave and
      calculate the phase velocity appropriately. 

PMID- 24109890
TI  - Evaluation of a 3D technique for quantifying neovascularization within plaques
      imaged by contrast enhanced ultrasound.
AB  - Intra-plaque neovascularization and inflammation are considered as important
      indicators of plaque vulnerability, which when ruptured, may cause stroke or
      acute myocardial infarction. The purpose of this research was to validate and
      evaluate a semi-automatic method, which allows quantification of carotid plaque
      neovascularization using contrast-enhanced ultrasound cines, thus enabling
      assessment of plaque vulnerability. The method detects contrast clusters in the
      images, and tracks them, to generate over time a path that portrays the
      neovasculature. It classifies the paths as either artifacts or 'blood vessels'
      and reconstructs the 3D arterial tree. Software-based phantom was developed to
      represent volumetric structures of the carotid lumen, the plaque, and 'objects'
      passing through the intra-plaque neovasculature. These 3D objects, which mimic
      microbubbles or clusters of microbubbles, were based on original 2D formations,
      imaged during clinical examinations using contrast-enhanced ultrasound. Within a
      plaque, several paths were constructed, representing flow inside blood vessels,
      and several isolated objects were added, representing artifacts. Different paths
      were generated, classified into 4 groups: separate paths, paths that merge at
      some point, paths that branch and intersecting paths. The phantom was used to
      generate sets of cines, which were then processed by the method. The method
      identified artifacts and different paths, which were then compared to the 'true'
      ones. Sixty-four 'objects' in 16 movies were examined. All of them were detected.
      79% of those objects were well tracked and classified to either artifacts or real
      blood vessels. The results of this study show that the method accurately
      identifies artifacts and paths, which allows reconstruction of intra-plaque
      vascular tree and quantification of the plaque neovasculature, which is
      associated with plaque vulnerability.

PMID- 24109891
TI  - Quantitative analysis of peri-tumor tissue elasticity based on shear-wave
      elastography for breast tumor classification.
AB  - For shear-wave elastography (SWE) images, the most common site of tumor
      associated stiffness is generally in the surrounding stroma rather than the tumor
      itself. The aim of this study is to assess the value of the peri-tumor tissue
      elasticity in the classification of breast tumors. SWE images of 106 breast
      tumors (65 benign, 41 malignant) were collected from 82 consecutive patients. By
      applying the image processing method, 5 elastographic features of the peri-tumor
      area (elasticity modulus mean, maximum, standard deviation, hardness degree and
      elasticity ratio) were computed to represent peri-tumor tissue elasticity. B-mode
      Breast Imaging Reporting and Data System (BI-RADS) were used for comparing the
      diagnostic performances between the grayscale US and color SWE images.
      Histopathologic results were used as the reference standard. The t-test, point
      biserial correlation coefficient and receiver operating characteristic (ROC)
      curve analysis were performed for statistical analysis. As a result, the Az
      values (area under ROC curve) were 0.92, 0.95, 0.94, 0.91, and 0.98 for the
      classifiers using the five elastographic features respectively, and 0.91 for BI
      RADS assessment. The results showed that the peri-tumor tissue elasticity could
      provide valuable information for breast tumor classification. 

PMID- 24109892
TI  - A regularization-free Young's modulus reconstruction algorithm for ultrasound
      elasticity imaging.
AB  - Ultrasound elasticity imaging aims to reconstruct the distribution of elastic
      modulus (e.g., Young's modulus) within biological tissues, since the value of
      elastic modulus is often related to pathological changes. Currently, most
      elasticity imaging algorithms face a challenge of choosing the value of the
      regularization constant. We propose a more applicable algorithm without the need
      of any regularization. This algorithm is not only simple to use, but has a
      relatively high accuracy. Our method comprises of a nonrigid registration
      technique and tissue incompressibility assumption to estimate the two-dimensional
      (2D) displacement field, and finite element method (FEM) to reconstruct the
      Young's modulus distribution. Simulation and phantom experiments are performed to
      evaluate the algorithm. Simulation and phantom results showed that the proposed
      algorithm can reconstruct the Young's modulus with an accuracy of 63~85%. 

PMID- 24109893
TI  - Quantitative elastography and its application to blood pressure estimation:
      theoretical and experimental results.
AB  - Elastography is a method that can be used to measure the elasticity of soft
      biological tissue and, ultimately, to detect cancerous tumors. In this paper,
      quantitative elastography is developed using a fast multi-scale approach. Results
      are presented in simulation and preliminary results are presented in experiment.
      The optimization methods of elastography are applied to measure noninvasively the
      arterial wall stiffness of a vessel as well as blood pressure. Simulation results
      are presented that confirm the accuracy of methods, and preliminary experimental
      results are presented that measure pressure within a cylindrical cavity in a
      phantom. Using ultrasound, these methods could provide noninvasive continuous
      measurement of blood pressure in major arteries and could give doctors another
      method with which to gather information about a patient's cardiovascular health. 

PMID- 24109894
TI  - Rotatable flexible neck-model for the evaluation of minimally invasive operation
      procedures with the help of an ultrasound-based navigation system.
AB  - Future minimally invasive neck surgery requires a navigation system adapted to
      the actual intraoperative bedding of the patient. The detection of the bedding
      caused tissue shift is essential for a safe orientation for the surgeons' new
      endoscopic operation procedures in neck surgery. It is essential to visualize the
      relation between important anatomic landmarks and operation instruments at any
      time. Within the scientific project SACAS we focus on developing an ultrasound
      supported navigation system based on preoperative imaging which considers the
      intraoperative tissue shift. A rotatable, flexible neck-model provides the basis
      for our analyses to evaluate the tissue shift and to invent the new navigation
      system for endoscopic neck surgery. The total registration error of the system
      was 2 mm. 

PMID- 24109895
TI  - A multiresolution framework for ultrasound image segmentation by combinative
      active contours.
AB  - We propose a novel multiresolution framework for ultrasound image segmentation in
      this paper. The framework exploits both local intensity and local phase
      information to tackle the degradations of ultrasound images. First,
      multiresolution scheme is adopted to build a Gaussian pyramid for each speckled
      image. Speckle noise is gradually smoothed out at higher levels of the pyramid.
      Then local intensity-driven active contours are employed to locate the coarse
      contour of the target from the coarsest image, followed by local phase-based
      geodesic active contours to further refine the contour in finer images. Compared
      with traditional gradient-based methods, phase-based methods are more suitable
      for ultrasound images because they are invariant to variations in image contrast.
      Experimental results on left ventricle segmentation from echocardiographic images
      demonstrate the advantages of the proposed model. 

PMID- 24109896
TI  - Evaluation of various speckle reduction filters on medical ultrasound images.
AB  - At present, ultrasound is one of the essential tools for noninvasive medical
      diagnosis. However, speckle noise is inherent in medical ultrasound images and it
      is the cause for decreased resolution and contrast-to-noise ratio. Low image
      quality is an obstacle for effective feature extraction, recognition, analysis,
      and edge detection; it also affects image interpretation by doctor and the
      accuracy of computer-assisted diagnostic techniques. Thus, speckle reduction is
      significant and critical step in pre-processing of ultrasound images. Many
      speckle reduction techniques have been studied by researchers, but to date there
      is no comprehensive method that takes all the constraints into consideration. In
      this paper we discuss seven filters, namely Lee, Frost, Median, Speckle Reduction
      Anisotropic Diffusion (SRAD), Perona-Malik's Anisotropic Diffusion (PMAD) filter,
      Speckle Reduction Bilateral Filter (SRBF) and Speckle Reduction filter based on
      soft thresholding in the Wavelet transform. A comparative study of these filters
      has been made in terms of preserving the features and edges as well as
      effectiveness of de-noising.We computed five established evaluation metrics in
      order to determine which despeckling algorithm is most effective and optimal for
      real-time implementation. In addition, the experimental results have been
      demonstrated by filtered images and statistical data table. 

PMID- 24109897
TI  - Dynamic perfusion assessment by contrast-enhanced ultrasound in blood-brain
      barrier disruption.
AB  - Recently, blood-brain barrier disruption (BBBD) has been performed by focused
      ultrasound (FUS) combining with microbubbles (MBs). The outcome of BBBD enhances
      local drug or gene delivery for improving the treatment efficiency of brain
      diseases. However, over-excitation of FUS may cause brain damage such as shutdown
      blood flow, intracerebral hemorrhage and brain edema. Therefore, it is essential
      to develop a an imaging system to assess dynamic perfusion changes during FUS
      induced BBBD process. Here, we used the high-frequency destruction/reperfusion
      contrast-enhanced imaging technique to observe the cerebral perfusion under the
      cases of with/without hemorrhage in BBBD procedure. The BBB was disrupted by a
      2.25 MHz FUS combining with MBs at 0.5-0.7 MPa (pulse repetition frequency: 1 Hz,
      pulse length: 1 ms, sonication time: 60 s). The results showed that the velocity
      of blood flow decreased after BBBD induced by FUS sonication. Particularly, the
      plateau of time-intensity curve was higher than prior to MBs destruction at 20 s
      after sonication and the blood flow would be obstructed due to the blood
      coagulates at 60s after sonication. The pattern of hemorrhagic damage caused by
      FUS can be monitored by the TIC. In addition, the location of blood flow velocity
      decrease was consistent with the areas of BBBD and the variation of blood flow
      depends on the applied acoustic pressure. In conclusion, the blood flow velocity
      changes have potential as an in vivo tool for quantifying the extent of the FUS
      induced BBBD and detecting intracerebral hemorrhage occurrence. 

PMID- 24109898
TI  - Automatic correction of rotating ultrasound bio microscopy acquisitions for the
      segmentation of the eye anterior segment.
AB  - We have developed a rotating 3D probe prototype in order to acquire the anterior
      segment of the eye in three dimensions. The acquisition accuracy has to be
      sufficient to allow for the use of automatic segmentation of the provided data,
      and thus generate a 3D structure of the eye, for which it could be easier to
      obtain measurements than in 2D images. We have created an image post processing
      scheme in order to compensate for vibrations and eye movements during acquisition
      that are associated with increased noise. These tools have been applied to 92
      volume datasets acquired on 21 patients in pre-operative conditions. Acquisition
      noise was reduced by 97% in specific conditions with respect to data acquired
      without correction.

PMID- 24109899
TI  - GPS-based outdoor activity pattern recording and analysis system.
AB  - In this paper, a recording and analysis system is designed and developed for
      outdoor activity patterns characterization. Some mental problems of aging,
      especially the occurrence of dementia, are not easily noticed in early stage. In
      this study, the proposed system is employed for outdoor activity patterns
      analysis. From the pattern analysis, the abnormal activity which is different
      from the usual patterns may be differentiated and warned. The proposed system
      integrates the tablet PC and GPS to track and to detect the occurrence of
      abnormal condition off-line. In the beginning, the sequence of GPS data is
      segmented in time frame, and represented in vector form for data reduction. Some
      filtering technique is also applied for noise reduction. 

PMID- 24109900
TI  - Evaluation of the android-based fall detection system with physiological data
      monitoring.
AB  - Aging population is considered to be major problem in modern healthcare. At the
      same time, fall incidents often occur among elderly and cause serious injuries
      affecting their independent living. This paper proposes a framework which uses
      mobile phone technology together with physiological data monitoring in order to
      detect falls. The system carries out collecting, storing and processing of
      acceleration data with further alarm generating and transferring all the
      measurements to remote caregiver. To perform evaluation, an experimental setup
      involving novice ice-skaters were carried out to obtain realistic fall data and
      examine the effects of falling on physiological parameters. A fall detection
      algorithm has been designed therefore to cope with large variations of movement
      in the torso. The online algorithm operating showed performance results of 90%
      specificity, 100% sensitivity and 94% accuracy.

PMID- 24109901
TI  - Interactive mobile system for smoking cessation.
AB  - Tobacco use remains the single largest preventable cause of death and disease in
      the United States. We developed an interactive mobile system to facilitate
      smoking cessation by identifying which stage of change the patient was currently
      in and creating a custom intervention and cessation action plan based upon their
      feedback and experience. It is designed to follow the patient through their
      smoking cessation experience and adapt to their changing attitudes over time. We
      piloted this program with 49 current smokers hospitalized at Johns Hopkins
      Hospital. The mobile smoking cessation system was generally well received by
      hospitalized patients. Improvement in attitudes and stage of change were noticed
      between pretest and posttest, suggesting an ability to help change patient's
      attitudes towards smoking and motivate them to quit. Providing real time decision
      support and tailoring the content shown to the patients to their personal profile
      can be a viable means in smoking cessation. 

PMID- 24109902
TI  - A mobile phone enabled health promotion program for middle-aged males.
AB  - The prevalence of chronic diseases among middle aged males outweigh their female
      counterparts in developed countries. To prevent this, delivery of health
      promotion programs targeting lifestyle modifications of physical activity and
      nutrition in middle-aged males has been essential, but often difficult. ManUp
      health promotion program was a recent initiative that uses current advances in
      information and communication technology (ICT) to reach the middle-aged males.
      One of the key components of the ICT approach was the development of smartphone
      application to enable middle-aged men to uptake the program with their own mobile
      phone. The smart phone application was aimed at providing varied level of
      challenges towards physical activity and healthy eating behavior, with
      interactive and motivational feedback SMS messages. The ManUp program was
      recently implemented and trialed in a randomized control trial in Gladstone and
      Rockhampton, Queens. This paper describes the components of the smart phone
      application integrated within the ManUp health promotion program. 

PMID- 24109903
TI  - An effective low-complexity multi-vital-signs compression technique for embedded
      link e-home healthcare.
AB  - Transplanting the existing e-home healthcare system to source-limited embedded
      link device for home-use health monitoring, intelligent medical diagnosis and
      wireless transmission is attractive. Yet, constrains of portable storage,
      computing and transmission promote the need of data compression for such
      applications. Existing compression techniques are mostly desktop-computer-based
      and computation-consuming, making them unsuitable for mobile device. To tackle
      such a bottleneck problem, this paper addresses an effective low-complexity multi
      vital-signs compression technique based on orthogonal polynomial decomposition
      (OPD) algorithm using Hermite functions. The technique is proposed and operated
      on the designated healthcare system with optimized parameters. Validated and
      tested with cardiovascular disease (CVD) diagnosis based on sphygmogram both
      experimentally and clinically, the proposed technique achieves comparable good
      performance with distortion less than 2% and compression ratio up to 6, and
      preserves significant pathological features of multi-vital-signs for clinical
      diagnosis. The proposed technique is highly robust even for freaky and
      pathological signals. In addition, the compressed results reflecting
      morphological features can be directly adapted to the subsequent medical analysis
      without further decompression. 

PMID- 24109904
TI  - Somnography using unobtrusive motion sensors and Android-based mobile phones.
AB  - Sleep plays a fundamental role in the life of every human. The prevalence of
      sleep disorders has increased significantly, now affecting up to 50% of the
      general population. Sleep is usually analyzed by extracting a hypnogram
      containing sleep stages. The gold standard method polysomnography (PSG) requires
      subjects to stay overnight in a sleep laboratory and to wear a series of
      obtrusive devices. This work presents an easy to use method to perform
      somnography at home using unobtrusive motion sensors. Ten healthy male subjects
      were recorded during two consecutive nights. Sensors from the Shimmer platform
      were placed in the bed to record accelerometer data, while reference hypnograms
      were collected using a SOMNOwatch system. A series of filters were used to
      extract a motion feature in 30 second epochs from the accelerometer signals. The
      feature was used together with the ground truth information to train a Naive
      Bayes classifiers that distinguished wakefulness, REM and non-REM sleep.
      Additionally the algorithm was implemented on an Android mobile phone. Averaged
      over all subjects, the classifier had a mean accuracy of 79.0 % (SD 9.2%) for the
      three classes. The mobile phone implementation was able to run in realtime during
      all experiments. In future this will lead to a method for simple and unobtrusive
      somnography using mobile phones.

PMID- 24109905
TI  - Wearable diet monitoring through breathing signal analysis.
AB  - This paper presents the design, system structure and performance for a wireless
      and wearable diet monitoring system. Food and drink intake can be detected by the
      way of detecting a person's swallow events. The system works based on the key
      observation that a person's otherwise continuous breathing process is interrupted
      by a short apnea when she or he swallows as a part of solid or liquid intake
      process. We detect the swallows through the difference between normal breathing
      cycle and breathing cycle with swallows using a wearable chest-belt. Three
      popular machine learning algorithms have been applied on extracted time and
      frequency domain features. It is shown that high detection performance can be
      achieved with only few features. 

PMID- 24109906
TI  - Feasibility for the enhancement of an online support system for persons with
      metabolic syndrome, aimed at applications for ischemic heart disease and heart
      failure.
AB  - Previously, we developed of an online support system for persons with metabolic
      syndrome. In this study, we investigated the possibility of enhancing our system
      for applications in ischemic heart disease (IHD) and heart failure (HF). The main
      causes of IHD are obesity, hypertension, arteriosclerosis, hyperglycemia and
      other metabolic disorders. These conditions are related to lifestyle issues, such
      as diet and exercise. Dietary management becomes more difficult as the patient's
      condition worsens. We primarily focused on behavior changes. To raise the user's
      awareness of food intake, we improved a number of functions of the developed
      system: an entry of the user's lifestyle information, a calculation of the total
      calorie intake and a reference of food model pictures in 80 kcal standard
      quantities. IHD encompasses many of the causes of HF. Management tools
      appropriate for HF are few. We describe the main functions of our system and
      promote self-management as a requirement for IHD and HF. We expect that the
      framework of our system is applicable to the management of patients with chronic
      HF. 

PMID- 24109907
TI  - Wegoto: A Smartphone-based approach to assess and improve accessibility for
      wheelchair users.
AB  - This paper proposes a description of a Smartphone-based approach to assess and
      improve accessibility for wheelchair users. The developed system employs a
      dedicated Smartphone application that records various complementary sensor
      measurements (acceleration, deceleration, inclination, orientation, speed, GPS
      position) and permits obstacle denunciation. Then, accessibility information are
      reported on maps in a Geographic Information System which can calculate the most
      accessible route for wheelchair users taking into account their profiles and
      capabilities. A case study involving a wheelchair-dependent paraplegic was
      performed to preliminary assess the feasibility of our Smartphone-based approach
      to provide an accessibility index for wheelchair users. Although preliminary, our
      results do suggest that the Wegoto system could be used as an innovative
      assistive navigation system for wheelchair users and ultimately could help to
      improve their autonomy and quality of life. 

PMID- 24109908
TI  - Evaluation of a Smartphone-based audio-biofeedback system for improving balance
      in older adults--a pilot study.
AB  - This study was designed to assess the effectiveness of a Smartphone-based audio
      biofeedback (ABF) system for improving balance in older adults. This so-called
      "iBalance-ABF" system that we recetly developed is "all-inclusive" in the sense
      that its three main components of a balance prosthesis, (i) the sensory input
      unit, (ii) the processing unit, and (iii) the sensory output unit, are entirely
      embedded into the Smartphone. The underlying principle of this system is to
      supply the user with supplementary information about the medial-lateral (ML)
      trunk tilt relative to a predetermined adjustable "dead zone" through sound
      generation in earphones. Six healthy older adults voluntarily participated in
      this pilot study. Eyes closed, they were asked to stand upright and to sway as
      little as possible in two (parallel and tandem) stance conditions executed
      without and with the use of the iBalance-ABF system. Results showed that, without
      any visual information, the use of the Smartphone-based ABF allowed the older
      healthy adults to significantly decrease their ML trunk sway in the tandem stance
      posture and to mitigate the destabilizing effect induced by this particular
      stance. Although an extended study including a larger number of participants is
      needed to confirm these data, the present results are encouraging. They do
      suggest that Smartphone-based ABF system could be used for balance training and
      rehabilitation therapy in older adults. 

PMID- 24109909
TI  - Improvement of the dual-heat-flux method for deep body temperature measurement
      based on a finite element model.
AB  - Based on finite element method, this study was dedicated to improve the
      performance of the newly proposed dual-heat-flux method (DHF) for noninvasive
      deep body temperature (DBT) measurement. This study focused mainly on the
      dimensions, e.g., the height and radius, of the probe of DHF to improve its
      performance, in terms of the measurement depth beneath the skin. This paper was
      also engaged in confirmation of the improved probe's performance on a
      physiological significant temperature range, 35 to 40  degrees C. The results
      showed that a probe with lower in height and larger in radius would have better
      performance. It suggests that we should reduce the height of the probe to half of
      the original and keep the radius unchanged for a better performance. 

PMID- 24109910
TI  - Statistical characterization of the dynamic human body communication channel at
      45 MHz.
AB  - The dynamic human body communication (HBC) propagation channel at 45 MHz was
      statistical characterized in this paper. A large amount of measurement data has
      been gathered in practical environment with real activities -treadmill running at
      different speeds in a lab room. The received power between two lower legs was
      acquired from three volunteers, with more than 60,000 snap shot of data in total.
      The statistical analyses confirmed that the HBC propagation channel at 45 MHz
      followed the Gamma and Lognormal distributions at the slower (2 km/h and 4 km/h)
      and faster (6 km/h and 8 km/h) running activities, respectively. The channel is
      insensitive to body motion with the maximum average fade duration is 0.0413 s and
      the most averaging bad channel duration time being less than 60 ms with the
      percentage of the bad channel duration time being less than 4.35%.

PMID- 24109911
TI  - Towards a smart Holter system with high performance analogue front-end and
      enhanced digital processing.
AB  - Multiple-lead dynamic ECG recorders (Holter) play an important role in the
      earlier detection of various cardiovascular diseases. In this paper, we present
      the first several steps towards a 12-lead Holter system with high-performance AFE
      (Analogue Front-End) and enhanced digital processing. The system incorporates an
      analogue front-end chip (ADS1298 from TI), which has not yet been widely used in
      most commercial Holter products. A highly-efficient data management module was
      designated to handle the data exchange between the ADS1298 and the microprocessor
      (STM32L151 from ST electronics). Furthermore, the system employs a Field
      Programmable Gate Array (Spartan-3E from Xilinx) module, on which a dedicated
      real-time 227-step FIR filter was executed to improve the overall filtering
      performance, since the ADS1298 has no high-pass filtering capability and only
      allows limited low-pass filtering. The Spartan-3E FPGA is also capable of
      offering further on-board computational ability for a smarter Holter. The results
      indicate that all functional blocks work as intended. In the future, we will
      conduct clinical trials and compare our system with other state-of-the-arts. 

PMID- 24109912
TI  - Attempt for noninvasive evaluation of in vivo triglyceride in blood.
AB  - To find an early symptom of postprandial hyperlipidemia, we developed a technique
      to measure the change in triglyceride noninvasively. We examined the feasibility
      to measure the change in the triglyceride concentration as the change in the
      scattering coefficient of the blood. In an experiment, good correlation was
      obtained between the change in the triglyceride after a meal and the optical
      change. This suggested the feasibility of the noninvasive measurement of the
      triglyceride in blood. 

PMID- 24109913
TI  - Body Area Networks performance analysis using UWB.
AB  - The successful realization of a Wireless Body Area Network (WBAN) using Ultra
      Wideband (UWB) technology supports different medical and consumer electronics
      (CE) applications but stand in a need for an innovative solution to meet the
      different requirements of these applications. Previously, we proposed to use
      adaptive processing gain (PG) to fulfill the different QoS requirements of these
      WBAN applications. In this paper, interference occurred between two different
      BANs in a UWB-based system has been analyzed in terms of acceptable ratio of
      overlapping between these BANs' PG providing the required QoS for each BAN. The
      first BAN employed for a healthcare device (e.g. EEG, ECG, etc.) with a
      relatively longer spreading sequence is used and the second customized for
      entertainment application (e.g. wireless headset, wireless game pad, etc.) where
      a shorter spreading code is assigned. Considering bandwidth utilization and
      difference in the employed spreading sequence, the acceptable ratio of
      overlapping between these BANs should fall between 0.05 and 0.5 in order to
      optimize the used spreading sequence and in the meantime satisfying the required
      QoS for these applications. 

PMID- 24109914
TI  - Comparative evaluation of an ambulatory EEG platform vs. clinical gold standard.
AB  - Electroencephalography (EEG) testing in clinical labs makes use of large
      amplifiers and complex software for data acquisition. While there are new
      ambulatory electroencephalogram (EEG) systems, few have been directly compared to
      a gold standard system. Here, an ultra-low power wireless EEG system designed by
      Imec is tested against the gold standard Neuroscan SynAmps2 EEG system, recording
      simultaneously from the same laboratory cap prepared with electrode gel. The data
      was analyzed using correlation analysis for both time domain and frequency domain
      data. The analysis indicated a high Pearson's correlation coefficient
      (mean=0.957, median=0.985) with high confidence (mean P=0.002) for 10-second sets
      of data transformed to the frequency domain. The time domain results had
      acceptable Pearson's coefficient (mean=0.580, median =0.706) with high confidence
      (mean P=0.008). 

PMID- 24109915
TI  - Applying NISHIJIN historical textile technique for e-Textile.
AB  - The e-Textile is the key technology for continuous ambient health monitoring to
      increase quality of life of patients with chronic diseases. The authors introduce
      techniques of Japanese historical textile, NISHIJIN, which illustrate almost any
      pattern from one continuous yarn within the machine weaving process, which is
      suitable for mixed flow production. Thus, NISHIJIN is suitable for e-Textile
      production, which requires rapid prototyping and mass production of very
      complicated patterns. The authors prototyped and evaluated a few vests to take
      twelve-lead electrocardiogram. The result tells that the prototypes obtains
      electrocardiogram, which is good enough for diagnosis. 

PMID- 24109916
TI  - Forward kinematics using IMU on-body sensor network for mobile analysis of human
      kinematics.
AB  - The feasibility of large network inertial measurement units (IMUs) are evaluated
      for purposes requiring feedback. A series of wireless IMUs were attached to a
      human lower-limb laboratory model outfitted with joint angle encoders. The goal
      was to discover if large networks of wireless IMUs can give realtime joint
      orientation data while still maintaining an acceptable degree of accuracy. 

PMID- 24109917
TI  - System development and performance evaluation on detection schemes for UWB-IR
      implant communications.
AB  - Ultra wideband-impulse radio (UWB-IR) transmission is one of promising
      transmission technologies in implant body area networks (BANs). Although some
      studies have investigated the channel model and communication architecture in
      implant BANs, no study quantitatively shows the feasibility of UWB-IR
      communication in the human body with actual developed transceivers at a high data
      rate. In this paper, we focus on experimental evaluation of the correlation
      detection (coherent detection) and the energy detection (non-coherent detection)
      for UWB-IR transmission with multi-pulse position modulation (MPPM). For this
      purpose, we develop a UWB-IR communication system with MPPM scheme, and
      experimentally evaluate the transmission performance of the developed systems
      with the two different detection schemes. In addition to the experimental
      evaluation, we also theoretically analyze the bit error rate (BER) performance by
      using Gaussian approximation. From the experimental results, the developed system
      has achieved a BER of 10(-2) at the propagation loss of 75 dB with a data rate of
      2 Mbps in the correlation detection. This result shows the feasibility of
      reliable UWB-IR communication in actual implant BANs.

PMID- 24109918
TI  - A study on reception electrodes for the vital-sign monitor using near-field intra
      body communication enhanced by spread spectrum technique.
AB  - As a novel vital sign monitor, we have developed wireless ECG monitoring system
      with Near-field intra-body communication (NF-IBC) technique. However, it was hard
      to ensure communication reliability because transmission channel is noisy and
      unstable. In order to solve the problem, we utilize spread spectrum (SS), which
      is known as robust communication technique even through poor transmission
      channel. In previous study, we have already developed an ECG monitor using NF-IBC
      enhanced by SS. In this paper, we evaluated on structure of the reception
      electrode for reliable communication. Based on the evaluations with bit error
      rate, we suggested the reception electrode structure which can keep the
      communication reliability. As the results we considered that we can expand the
      reception electrode up to 2.25 m(2). Moreover, we proposed the structure of the
      reception electrodes that can keep the communication reliability. Finally we
      suggested how to use the SS NF-IBC vital-sign monitor in room that larger than
      2.25 m(2), and we had shown the practicability of the systems.

PMID- 24109919
TI  - Effect of the antenna-body distance on the on-ext and on-on channel link path
      gain in UWB WBAN applications.
AB  - This paper investigates the effect of the operation distance (i.e., practical
      use) between an antenna and a human body on wireless body area network (WBAN)
      channel path gain. Different use cases in WBAN on-external (ext) and on-on links
      with different antenna-body distances for ultra wideband (UWB) technology are
      considered. These studies are carried out with two types of planar UWB antennas
      in the vicinity of a real human body. Corresponding scenarios are repeated by
      computer simulations, and differences between these environs (i.e., challenges in
      the modelling of the measurement situation) are analysed and discussed. 

PMID- 24109920
TI  - M-BRIDGE: Wireless portable onbody aggregator and visualizer system for Wireless
      Body Sensor Network.
AB  - Advances made in electronics, intelligent and wireless technologies enable
      individuals to self-observe their health states anywhere anytime. The shift in
      self care becomes a promising paradigm to alleviate burdens on centralized
      institutional care. As a result, Wireless Body Sensor Network (WBSN) personal
      health solutions can be seen increasingly although medical community still has
      concerns on their usability and applicability. Especially, there is still lacking
      in portable wireless wearable gateway to integrate WBSN into existing healthcare
      solutions. To fulfill this gap, we design and develop MobilE on-Body aGgregator
      and vIsualizer Device (M-BRIDGE) system using Android smart phone. Our proposed
      solution fully supports the needs of flexible device interfacing, data
      aggregation, efficient data distribution and user-friendly visualization. We also
      explain how M-BRIDGE's unique features and operation can complement with and
      fulfill the deficiency of existing WBSN healthcare solutions. We finally present
      the details of implementation and technical evaluation as well as discussion on
      the potential issues and future works. 

PMID- 24109921
TI  - A compensation method to improve the performance of IPI-based entity recognition
      system in body sensor networks.
AB  - Security of wireless body sensor networks (BSNs) with telemedicine applications
      remains a crucial issue. A family of novel biometrics schemes has been recently
      proposed for node recognition and cryptographic key distribution without any pre
      deployment in BSNs, where dynamic entity identifiers (EIs) generated from
      physiological signals captured by individual sensor nodes are used for nodes to
      recognize each other. As the recognition performance of EIs determines the
      maximal performance that can be achieved in such biometric systems, several kinds
      of EI generation schemes have been proposed. The inter-pulse intervals based EI
      generation scheme is more promising for such applications in actual scenarios
      because of its acceptable recognition performance. However, it was found that
      such generated EIs by true pairs of nodes, i.e. two nodes from the same BSN, have
      some error pattern which could be considered while doing node recognition or key
      distribution for an improved success rate. To address the problem, this work
      proposes an error-correcting code based compensation method which can be easily
      combined together with the key distribution process to achieve an improved
      recognition performance. Results of statistical analysis with experimental data
      collected from 14 subjects show that the bit difference between EIs from true
      pairs of nodes can be effectively reduced with the proposed method. 

PMID- 24109922
TI  - Estimate of the fetal temperature increase due to UHF RFID exposure.
AB  - Exposure from electromagnetic (EM) devices has increased during the last decades
      due to the rapid development of new technologies. Among them, radiofrequency
      identification (RFID) applications are used in almost every aspect of everyday
      life, which could expose people unselectively. This scenario could pose potential
      risks for certain groups of general population, such as pregnant women, who are
      more sensitive to thermal effects produced by EM exposure. In this paper, the
      temperature rise at the steady state in two pregnant women models exposed to UHF
      RFID has been assessed. Results show that heating of tissues is far from the
      threshold of biological effects indicated by radiation protection guidelines. 

PMID- 24109923
TI  - Road information collection and sharing system.
AB  - Walking is an important factor in good health, and people derive many benefits
      from travelling by foot. However, walking entails risks such as traffic accidents
      and falls. If people recognize specific risks before walking, then they may avoid
      such accidents. This paper proposes a road information collection and sharing
      tool for the public. The proposed system stores passive risks from the properties
      of the landscape and active risks identified by people. Moreover, it realizes an
      easy way to access such risk information. When people know and avoid these risks,
      they will be able to walk safely. 

PMID- 24109924
TI  - The discriminant analysis of the voice expression of emotion--focus on the
      nursing experience-.
AB  - The characteristics of emotional expression in everyday life vary significantly
      depending on one's life experiences, role in society, and other factors,
      especially special occupation experiences. We focus on the nursing experience.
      The purpose of this study is to establish a method to discriminate voice of
      nurse's emotion. We performed the pronunciation experiment at first and through
      the sound analysis, extracted the effective speech parameters. For make clear of
      the differences of these parameters between emotions and discriminate emotions,
      we performed the multiple comparisons and discriminant analysis. In the result,
      found that the speech parameters different between emotions and these affected
      parameters are different at two groups based on nursing experience. In four
      emotions of our study, the Sadness is easy discriminant emotion; the Joy is most
      difficult to discriminate. Through the discriminant analysis, found two stable
      speech parameters. 

PMID- 24109925
TI  - Applications of software-defined radio (SDR) technology in hospital environments.
AB  - A software-defined radio (SDR) is a radio communication system where the major
      part of its functionality is implemented by means of software in a personal
      computer or embedded system. Such a design paradigm has the major advantage of
      producing devices that can receive and transmit widely different radio protocols
      based solely on the software used. This flexibility opens several application
      opportunities in hospital environments, where a large number of wired and
      wireless electronic devices must coexist in confined areas like operating rooms
      and intensive care units. This paper outlines some possible applications in the
      2360-2500 MHz frequency band. These applications include the integration of
      wireless medical devices in a common communication platform for seamless
      interoperability, and cognitive radio (CR) for body area networks (BANs) and
      wireless sensor networks (WSNs) for medical environmental surveillance. The
      description of a proof-of-concept CR prototype is also presented. 

PMID- 24109926
TI  - Finite element analysis of the contact interface between trans-femoral stump and
      prosthetic socket.
AB  - Transfemoral amputees need prosthetic devices after amputation surgery, and the
      interface pressure between the residual limb and prosthetic socket has a
      significant effect on an amputee's satisfaction and comfort. The purpose of this
      study was to build a nonlinear finite element model to investigate the interface
      pressure between the above-knee residual limb and its prosthetic socket. The
      model was three-dimensional (3D) with consideration of nonlinear boundary
      conditions. Contact analysis was used to simulate the friction conditions between
      skin and the socket. The normal stresses up to 80.57 kPa at the distal end of the
      soft tissue. The longitudinal and circumferential shear stress distributions at
      the limb-socket interface were also simulated. This study explores the influences
      of load transfer between trans-femoral residual limb and its prosthetic socket. 

PMID- 24109927
TI  - Estimating personalized risk ranking using laboratory test and medical knowledge
      (UMLS).
AB  - In this paper, we introduce a Concept Graph Engine (CG-Engine) that generates
      patient specific personalized disease ranking based on the laboratory test data.
      CG-Engine uses the Unified Medical Language System database as medical knowledge
      base. The CG-Engine consists of two concepts namely, a concept graph and its
      attributes. The concept graph is a two level tree that starts at a laboratory
      test root node and ends at a disease node. The attributes of concept graph are:
      Relation types, Semantic types, Number of Sources and Symmetric Information
      between nodes. These attributes are used to compute the weight between laboratory
      tests and diseases. The personalized disease ranking is created by aggregating
      the weights of all the paths connecting between a particular disease and
      contributing abnormal laboratory tests. The clinical application of CG-Engine
      improves physician's throughput as it provides the snapshot view of abnormal
      laboratory tests as well as a personalized disease ranking. 

PMID- 24109928
TI  - Authoring tool: acquiring sharable knowledge for Smart CDSS.
AB  - Clinical Decision Support Systems (CDSS) assist clinicians in making clinical
      decisions by using experts' knowledge stored in the knowledge base. However,
      sharing and reusing the knowledge is a challenging task. Many systems are
      developed to facilitate sharing of medical knowledge and allow its reusability.
      These systems are compliant to standard approaches such as HL7 Arden Syntax and
      HL7 CDA (Clinical Document Architecture) to incorporate medical logic in standard
      format. The main drawback with these systems is the complicated procedure in the
      development of clinical knowledge by ordinary clinicians. The proposed research
      work is focusing on developing authoring tool that creates sharable clinical
      knowledge base using standards such as HL7 Arden Syntax, HL7 vMR and HL7 CDA.
      Moreover, the authoring tool provides user friendly GUI to facilitate clinicians
      in creating standard based executable clinical knowledge base. We are closely
      working with oncologists and clinicians of a prominent cancer hospital to deploy
      the tool for Head and Neck Cancer diagnosis and treatment recommendations. 

PMID- 24109929
TI  - TCIA: An information resource to enable open science.
AB  - Reusable, publicly available data is a pillar of open science. The Cancer Imaging
      Archive (TCIA) is an open image archive service supporting cancer research. TCIA
      collects, de-identifies, curates and manages rich collections of oncology image
      data. Image data sets have been contributed by 28 institutions and additional
      image collections are underway. Since June of 2011, more than 2,000 users have
      registered to search and access data from this freely available resource. TCIA
      encourages and supports cancer-related open science communities by hosting and
      managing the image archive, providing project wiki space and searchable metadata
      repositories. The success of TCIA is measured by the number of active research
      projects it enables (>40) and the number of scientific publications and
      presentations that are produced using data from TCIA collections (39). 

PMID- 24109930
TI  - Planning of hepatectomy for tumor resection: resection surface construction and
      optimization.
AB  - An interactive liver surgery planning system has been developed to construct and
      optimize the resection plan. With this system, the segmentation results of the
      liver and its components (such as tumors and vessels) are comprehensively
      visualized for surgeons to have an intuitive understanding of the internal
      anatomical structure of the liver. This system will also allow surgeons to
      interactively create and modify a resection plan on the virtual liver model. The
      resection surface, whose boundary is a closed curve, will be automatically
      constructed with the safe resection margins of tumors. Different from other
      systems, our developed system is able to generate the safety margins to all
      tumors. During surgery, a larger resection surface may cause potentially more
      bleeding and other complications. Therefore, area minimization is applied during
      the resection surface construction by adopting the minimal area mesh, which is a
      smooth surface with minimal area. After these virtual modifications, the
      resultant resection surface indicates the route to cut the liver for tumor
      removal. The volumes for both resected liver and residual liver are calculated
      for clinical decision making. 

PMID- 24109931
TI  - Predicting post-treatment survivability of patients with breast cancer using
      Artificial Neural Network methods.
AB  - In the last decade, the use of data mining techniques has become widely accepted
      in medical applications, especially in predicting cancer patients' survival. In
      this study, we attempted to train an Artificial Neural Network (ANN) to predict
      the patients' five-year survivability. Breast cancer patients who were diagnosed
      and received standard treatment in one hospital during 2000 to 2003 in Taiwan
      were collected for train and test the ANN. There were 604 patients in this
      dataset excluding died not in breast cancer. Among them 140 patients died within
      five years after their first radiotherapy treatment. The artificial neural
      networks were created by STATISTICA((r)) software. Five variables (age, surgery
      and radiotherapy type, tumor size, regional lymph nodes, distant metastasis) were
      selected as the input features for ANN to predict the five-year survivability of
      breast cancer patients. We trained 100 artificial neural networks and chose the
      best one to analyze. The accuracy rate is 85% and area under the receiver
      operating characteristic (ROC) curve is 0.79. It shows that artificial neural
      network is a good tool to predict the five-year survivability of breast cancer
      patients. 

PMID- 24109932
TI  - Machine learning approach to an otoneurological classification problem.
AB  - In this paper we applied altogether 13 classification methods to otoneurological
      disease classification. The main point was to use Half-Against-Half (HAH)
      architecture in classification. HAH structure was used with Support Vector
      Machines (SVMs), k-Nearest Neighbour (k-NN) method and Naive Bayes (NB) methods.
      Furthermore, Multinomial Logistic Regression (MNLR) was tested for the dataset.
      HAH-SVM with the linear kernel achieved clearly the best accuracy being 76.9%
      which was a good result with the dataset tested. From the other classification
      methods HAH-k-NN with cityblock metric, HAH-NB and MNLR methods achieved above
      60% accuracy. Around 77% accuracy is a good result compared to previous
      researches with the same dataset. 

PMID- 24109933
TI  - Preference based load balancing as an outpatient appointment scheduling aid.
AB  - Load balancing is a performance improvement aid in various applications of
      distributed systems. In this paper we propose a preference based load balancing
      strategy as a scheduling aid in an outpatient clinic of an online medical
      consultation system. The performance objectives are to maximizing throughout and
      minimizing waiting time. Patients will provide a standard set of preferences
      prior to scheduling an appointment. The preferences are rated on to a scale and
      each service request will have a respective preference score. The available
      doctors will also be classified into classes based on their clinical expertise
      and the nature of the past diagnosis and the types of patients consulted. The
      preference scores will then be mapped on to each class and the appointment will
      be scheduled. The proposed scheme was modeled as a queuing system in Matlab.
      Matlab SimEvents library modules were used for constructing the model.
      Performance was analysed based on the average waiting time and utilization. The
      results revealed that the preference based load balancing scheme markedly reduce
      the waiting time and significantly improve the utilization under different load
      conditions. 

PMID- 24109934
TI  - Steganography-based access control to medical data hidden in electrocardiogram.
AB  - Steganographic techniques allow secret data to be embedded inside another host
      data such as an image or a text file without significant changes to the quality
      of the host data. In this research, we demonstrate how steganography can be used
      as the main mechanism to build an access control model that gives data owners
      complete control to their sensitive cardiac health information hidden in their
      own Electrocardiograms. Our access control model is able to protect the privacy
      of users, the confidentiality of medical data, reduce storage space and make it
      more efficient to upload and download large amount of data. 

PMID- 24109935
TI  - RespDoc: a new clinical decision support system for childhood asthma management
      based on Fraction of Exhaled Nitric Oxide (FeNO) measurements.
AB  - The use of Fraction of Exhaled Nitric Oxide (FeNO) for measurement of
      inflammation in the respiratory system is a good way to assess the level of
      asthma in children. In this paper we present a new Clinical Decision Support
      System (CDSS) for Childhood Asthma Management based on FeNO, which is named
      RespDoc. The core of RespDoc is a decision making algorithm and a patient's
      monitoring process that are extensively analyzed in the paper. The performance of
      RespDoc is tested through the process and assessment of archived patients' data. 

PMID- 24109936
TI  - Fuzzy logic applied to a Patient Classification System.
AB  - The optimization of the clinical staff resources is a very complicated task that
      can be supported by a set of tools called Patient Classification Systems (PCS).
      These methods allow the evaluation of the correct number of nurses and healthcare
      workers needed in order to guarantee an appropriate care level. 

PMID- 24109937
TI  - Adverse event prediction in patients with left ventricular assist devices.
AB  - This work presents the Treatment Tool, which is a component of the Specialist's
      Decision Support Framework (SDSS) of the SensorART platform. The SensorART
      platform focuses on the management of heart failure (HF) patients, which are
      treated with implantable, left ventricular assist devices (LVADs). SDSS supports
      the specialists on various decisions regarding patients with LVADs including
      decisions on the best treatment strategy, suggestion of the most appropriate
      candidates for LVAD weaning, configuration of the pump speed settings, while also
      provides data analysis tools for new knowledge extraction. The Treatment Tool is
      a web-based component and its functionality includes the calculation of several
      acknowledged risk scores along with the adverse events appearance prediction for
      treatment assessment. 

PMID- 24109938
TI  - Variations of snoring properties with macro sleep stages in a population of
      Obstructive Sleep Apnea patients.
AB  - Snoring is common in Obstructive Sleep Apnea (OSA) patients. Snoring originates
      from the vibration of soft tissues in the upper airways (UA). Frequent UA
      collapse in OSA patients leads to sleep disturbances and arousal. In a routine
      sleep diagnostic procedure, sleep is broadly divided into rapid eye movement
      (REM), non-REM (NREM) states. These Macro-Sleep States (MSS) are known to be
      involved with different neuromuscular activities. These differences should
      influence the UA mechanics in OSA patients as well as the snoring sound (SS). In
      this paper, we propose a logistic regression model to investigate whether the
      properties of SS from OSA patients can be separated into REM/NREM group.
      Analyzing mathematical features of more than 500 SS events from 7 OSA patients,
      the model achieved 76% (+/- 0.10) sensitivity and 75% (+/- 0.10) specificity in
      categorizing REM and NREM related snores. These results indicate that snoring is
      affected by REM/NREM states and proposed method has potential in differentiating
      MSS. 

PMID- 24109939
TI  - An acoustic method of automatically evaluating patient inhaler technique.
AB  - Chronic respiratory diseases such as asthma and chronic obstructive pulmonary
      disease (COPD) affect millions of people worldwide. Inhalers are devices utilized
      to deliver medication in small doses directly to the airways in the treatment of
      asthma and COPD. Despite the proven effectiveness of inhaler medication in
      controlling symptoms, many patients suffer from technique errors leading to
      decreased levels of medication efficacy. This study employs a recording device
      attached to a commonly used dry powder inhaler (DPI) to obtain the acoustic
      signals of patients taking their inhaler medication. The audio files provide
      information on how a patient uses their inhaler over a period of one month.
      Manually listening to such a large quantity of audio files would be a time
      consuming and monotonous process and therefore an algorithm that could
      automatically carry out this task would be of great benefit. An algorithm was
      thus designed and developed to detect inhalation, exhalation and blister events
      in the audio signals, analyze the quantity of each event, the order in which the
      events took place and finally provide a score on the overall performance. The
      algorithm was tested on a dataset of 185 audio files obtained from five community
      dwelling asthmatic patients in real world environments. Evaluation of the
      algorithm on this dataset revealed that it had an accuracy of 92.8% in deciding
      the correct technique score compared to manual detection methods. 

PMID- 24109940
TI  - A study on EGG affected by viscosity and shear rate dependence of fluid and semi
      solid diets.
AB  - The purpose of this study is to clarify the relation among the viscosity values
      of semi-solid diets and the electrical mechanism of gastric motility. Firstly, a
      measurement procedure suitable for stomach physiology was proposed. A new
      measurement procedure lessened the psychological and physiological burdens of the
      subjects, and controlled the cycle of gastric activity of the subjects. And the
      dispersion of data for subjects was decreased by this new method, in which the
      measurements were started after 4 hours fasting. Secondly, we prepared five
      grades of viscosities of fluid to semi-solid diets from low to high viscosity (30
      mPa . s ~ 20000 mPa . s) mixed by five different amounts of two kinds of
      thickening agents. The measurements were performed for 8 healthy volunteer
      subjects. By evaluating DPr (Dominant Power ratio: Ratio of post/pre-prandial DP
      values), a significant increment by ingestion of high viscosity semi-solid diets
      was confirmed in both kinds of thickening agents. DFD (Dominant Frequency
      Dispersion) was significantly decreased in both high viscosity semi-solid diets.
      Thus, these results suggested that gastric activity was physiologically
      stimulated and the cycle of gastric activity became stable by ingestion of high
      viscosity diets. The results showed that an electrophysiological phenomenon in
      the evaluation of electrogastrography (EGG) is affected by the viscosity of
      diets, and also suggested that the difference in the shear rate dependence of
      diets was not really significant to the electrical behavior of gastric motility.

PMID- 24109941
TI  - 3D characterization and trend analysis of scents from EEG recordings of repeated
      scent exposure.
AB  - Scent plays an important role in influencing the brain and has been commonly used
      in psychological research. Much of such research has been conducted without the
      use of electroencephalography (EEG) to measure the response of the human brain to
      scent stimulus. Recent studies have involved the use of EEG to perform
      comparative studies on how different scents can affect brain activity. However,
      little has been done to analyze the trend of brain activity when a subject is
      repeatedly exposed to the same scent. This paper discusses the use of 4 features 
      Entropy Difference, Entropy Ratio, Entropy Time and Root Mean Square (RMS) to
      perform trend analysis of EEG signals in a repeated scent-exposure setting. The
      results show that different types of scents cause the brain to be stimulated at
      different degrees for each repeated exposure, giving rise to different trend
      patterns. It is also observed that the 4 features give similar trends for the
      same scent. This similarity allows us to combine the 4 features by forming a
      feature vector and plotting them in 3 dimensional (3D) space, using 3 repeated
      scent exposures as the axes. The region of space where the feature vector lies is
      represented by an ellipsoid, which can be used to characterize a particular
      scent. Unlike previous work, which did not characterize scent from EEG
      recordings, this paper investigates the different trends of scent after its
      repeated exposure to the human subject and by using the 3D representation to
      characterize the scent. 

PMID- 24109942
TI  - Can an algorithm predict a voiding contraction in unconscious rats?
AB  - Urinary incontinence (UI) is a very common and serious disorder which can be
      classified in stress and urge incontinence, the latter mainly caused by an
      overactive bladder (OAB). A definitive treatment for OAB does not exist yet due
      to its complex nature. Therefore, more attention must be focused on improving the
      patient's quality of life. A device able to alert the patient to development of a
      voiding contraction would be highly desirable, enabling actions to avoid
      incontinence. The main hypothesis of this work is that a voiding contraction is
      preceded by a consistent change in the pattern of intravesical pressure (p(ves)).
      We developed an algorithm based on frequency analysis of p(ves) recordings of two
      strains of rats whose bladders were first filled with saline (S fillings) and
      then with acetic acid (AA fillings); the latter was used as model for OAB in
      rats. The algorithm was designed to provide an alarm when an increase in the
      range 0.2-0.6 Hz of the amplitude spectrum was detected. The accuracy of the
      algorithm has been tested and quantified, successful alarms were those taking
      place within fifty seconds before the start of voiding. Although the results are
      still very preliminary, due to the low number of tested animals, they seem
      encouraging since, in five rats, only one showed a percentage of success lower
      than 50%, with one rat reaching 100%. The accuracy of the algorithm is affected
      by the choice of the values for the controlling parameters, which have been set
      the same for all rats; future developments might include individual values for
      each rat.

PMID- 24109943
TI  - A robust EC-PC spike detection method for extracellular neural recording.
AB  - This paper models signals and noise for extracellular neural recording. Although
      recorded data approximately follow Gaussian distribution, there are slight
      deviations that are critical for signal detection: a statistical examination of
      neural data in Hilbert space shows that noise forms an exponential term while
      signals form a polynomial term. These two terms can be used to estimate a spiking
      probability map that indicates spike presence. Both synthesized data and animal
      data are used for the detection performance evaluation and comparison against
      other popular detectors. Experimental results suggest that the predicted spiking
      probability map is consistent with the benchmark and work robustly with different
      recording preparations. 

PMID- 24109944
TI  - Detection of sleep-disordered breating with Pressure Bed Sensor.
AB  - A Pressure Bed Sensor (PBS) can offer an unobtrusive method for sleep monitoring.
      This study focuses on the detection of the sleep related breathing disorders
      using a PBS in comparison to the methods used in a sleep laboratory. A newly
      developed PCA modeling approach for the eight sensor signals of the PBS is
      evaluated using the Reduced Respiratory Amplitude Index (RRAI) as a central
      measure. The method computes the respiration amplitude with the Hilbert
      transform, and then detects the events based on a 20% amplitude reduction from
      the baseline signal. A similar calculation was used for the sleep laboratory RIP
      measurements, and both PBS and RIP were compared against the reference based on
      the nasal flow signal. In the reference RRAI method, the respiratory-disordered
      events were obtained using RemLogic respiration analyzer to detect over 50%
      amplitude reduction in the nasal respiratory flow, but removing the RemLogic
      standard hypopnea event associations on the oxygen desaturation events and the
      sleep arousals. The movement artifacts were automatically detected based on the
      movement activity signal of the PBS. Twenty-five (25) out of 28 patients were
      finally analysed. On average 87% of a night measurement has been covered by the
      system. The correlation coefficient was 0.92 between the PBS and the reference
      RRAI, and the performance of the PBS was similar with the RIP belts. Classifying
      the severity of the sleep related breathing by dividing RRAI in groups according
      to the severity criteria, the sensitivity was 92% and the specificity was 70% for
      the PBS. The results suggest that PBS recording can provide an easy and un
      obstructive alternative method for the detection of the sleep disordered
      breathing and thus has a great promise for the home monitoring. 

PMID- 24109945
TI  - Applicability of the "Emotiv EEG Neuroheadset" as a user-friendly input
      interface.
AB  - We aimed to develop an input interface by using the P3 component of visual event
      related potentials (ERPs). When using electroencephalography (EEG) in daily
      applications, coping with ocular-motor artifacts and ensuring that the equipment
      is user-friendly are both important. To address the first issue, we applied a
      previously proposed method that applies an unmixing matrix to acquire independent
      components (ICs) obtained from another dataset. For the second issue, we
      introduced a 14-channel EEG commercial headset called the "Emotiv EEG
      Neuroheadset". An advantage of the Emotiv headset is that users can put it on by
      themselves within 1 min without any specific skills. However, only a few studies
      have investigated whether EEG and ERP signals are accurately measured by Emotiv.
      Additionally, no electrodes of the Emotiv headset are located over the
      centroparietal area of the head where P3 components are reported to show large
      amplitudes. Therefore, we first demonstrated that the P3 components obtained by
      the headset and by commercial plate electrodes and a multipurpose bioelectric
      amplifier during an oddball task were comparable. Next, we confirmed that eye
      blink and ocular movement components could be decomposed by independent component
      analysis (ICA) using the 14-channel signals measured by the headset. We also
      demonstrated that artifacts could be removed with an unmixing matrix, as long as
      the matrix was obtained from the same person, even if they were measured on
      different days. Finally, we confirmed that the fluctuation of the sampling
      frequency of the Emotiv headset was not a major problem. 

PMID- 24109946
TI  - A mobile SSVEP-based brain-computer interface for freely moving humans: the
      robustness of canonical correlation analysis to motion artifacts.
AB  - Recently, translating a steady-state visual-evoked potential (SSVEP)-based brain
      computer interface (BCI) from laboratory settings to real-life applications has
      gained increasing attention. This study systematically tests the signal quality
      of SSVEP acquired by a mobile electroencephalogram (EEG) system, which features
      dry electrodes and wireless telemetry, under challenging (e.g. walking) recording
      conditions. Empirical results of this study demonstrated the robustness of
      canonical correlation analysis (CCA) to movement artifacts for SSVEP detection.
      This demonstration considerably improves the practicality of real-life
      applications of mobile and wireless BCI systems for users actively behaving in
      and interacting with their environments. 

PMID- 24109947
TI  - Adventitious lung sounds imaging by ICA-TVAR scheme.
AB  - Adventitious lung sounds (ALS) as crackles and wheezes are present in different
      lung alterations and their automated characterization and recognition have become
      relevant. In fact, recently their 2D spatial distribution (SD) imaging has been
      proposed to help diagnose of pulmonary diseases. In this work, independent
      component analysis (ICA) by infomax was used to find crackles sources and from
      them to apply a time variant autoregressive model (TVAR) to count and imaging the
      ALS. The proposed methodology was assessed on multichannel LS recordings by
      embedding simulated fine crackles with known SD in recorded normal breathing
      sounds. Afterwards, the adventitious image of two patients with fibrosis and
      emphysema were obtained and contrasted with the classical pulmonary auscultation
      provided by a pneumologist. The results showed that combining ICA and TVAR leads
      to a robust methodology to imaging ALS. 

PMID- 24109948
TI  - De-noising the abdominal phonogram for foetal heart rate extraction: blind source
      separation versus empirical filtering.
AB  - This work explored the suitability of using the foetal phonocardiogram (FPCG)
      blindly separated from the abdominal phonogram as a source for foetal heart rate
      (FHR) measuring in antenatal surveillance. To this end, and working on a dataset
      of 15 abdominal phonograms, the FPCG was estimated by using two de-noising
      approaches (1) single-channel independent component analysis (SCICA) to produce
      FPCG(e) and (2) empirical filtering to produce FPCG(g). Next, the FPCGs were
      further processed to collect the beat-to-beat FHR and the resulting time-series
      (FCTG(e) and FCTG(g) were compared to the reference signal given by the abdominal
      ECG (FCTG(r)). Results are promising, the FPCG(e) gives rise to a FCTG(e) that
      resembles FCTG(r) and, most importantly, whose mean FHR value is statistically
      equivalent to that given by FCTG(r) (p > 0.05). Thus, the mean FHR value obtained
      from the FPCG(e), is likely to be equivalent to the value given by the abdominal
      ECG, which is especially significant since the FPCG(e) is retrieved from the
      noisy abdominal phonogram. Hence, as far as this study has gone, it can be said
      that, when using SCICA to de-noise the abdominal phonogram, the resulting FPCG is
      likely to become a useful source for FHR collection in antenatal surveillance.

PMID- 24109949
TI  - Dipole source analysis for readiness potential and field using simultaneously
      measured EEG and MEG signals.
AB  - Various source localization techniques have indicated the generators of each
      identifiable component of movement-related cortical potentials, since the
      discovery of the surface negative potential prior to self-paced movement by
      Kornhuber and Decke. Readiness potentials and fields preceding self-paced finger
      movements were recorded simultaneously using multichannel electroencephalography
      (EEG) and magnetoencephalography (MEG) from five healthy subjects. The cortical
      areas involved in this paradigm are the supplementary motor area (SMA)
      (bilateral), pre-SMA (bilateral), and contralateral motor area of the moving
      finger. This hypothesis is tested in this paper using the dipole source analysis
      independently for only EEG, only MEG, and both combined. To localize the sources,
      the forward problem is first solved by using the boundary-element method for
      realistic head models and by using a locally-fitted-sphere approach for spherical
      head models consisting of a set of connected volumes, typically representing the
      scalp, skull, and brain. In the source reconstruction it is to be expected that
      EEG predominantly localizes radially oriented sources while MEG localizes
      tangential sources at the desired region of the cortex. The effect of MEG on EEG
      is also observed when analyzing both combined data. When comparing the two head
      models, the spherical and the realistic head models showed similar results. The
      significant points for this study are comparing the source analysis between the
      two modalities (EEG and MEG) so as to assure that EEG is sensitive to mostly
      radially orientated sources while MEG is only sensitive to only tangential
      sources, and comparing the spherical and individual head models. 

PMID- 24109950
TI  - Comparison of functional network integrity in TBI and orthopedic
      controlpatientsusing graph-theoretical analysis.
AB  - The integrity of functional brain networks inpatients (n=12) diagnosed with
      traumatic brain injury (TBI) was compared to age-matched subjects (n=12) with
      orthopedic injury (OI) during a working memory task. A graph-theoretical analysis
      algorithm was developed and integrated into the AFNI software. Functional
      networks with correlations between time courses as edge-weights were
      automatically created and their integrity was quantified by determining the
      statistical significance of the following network parameters: diameter, density,
      clustering coefficient, average path length, two largest eigenvalues, spectral
      density, and minimum eccentricity. Network graphs using a spring-embedded layout
      (Cytoscape) and a 3D layout integrated into the anatomical space (Paraview) were
      created. Functional images were composed by color-coding the degree of each voxel
      (network node) and transformed into Talairach space. Using the AFNI Talairach
      atlas, degrees of distinct brain regions were quantified. Reduced averaged BOLD
      responses were found for the TBI group with a higher network integrity
      potentially as a compensatory mechanism. Regions of high functional connectivity
      varied in between groups with largest differences in the cerebellum, the temporal
      lobes and deep brain structures including the lentiform nucleus, caudate and
      thalamus. 

PMID- 24109951
TI  - Sensitivity of MRI for directly detecting neuronal electrical activities in rat
      brain slices.
AB  - We developed an experimental setup for magnetic resonance imaging (MRI) of rat
      brain slices maintained in a hemoglobin-free medium and showed that the MRI
      system has a sensitivity to magnetic fields of 10(-11) T. The originally
      developed non-magnetic sample holder consisted of a microelectrode array for
      recording neuronal potentials and perfusing channels for the medium. Because of
      the hemoglobin-free condition, the magnetic fields could be distinguished from
      the baseline signal fluctuations due to hemoglobin. A theoretical estimation of
      the signal-to-noise ratio showed a sensitivity of 3.3 * 10(-10) T. Parameter
      optimization using a 7-T MRI system with the developed sample holder resulted in
      an experimental sensitivity of 4.0 * 10(-10) T. These MRI sensitivities
      potentially enable us to detect weak magnetic fields arising from neuronal
      activities, and are sufficiently high for detecting neuronal magnetic fields of
      1.4 * 10(-11) T generated in rat brain slices by averaging signals 810 times. 

PMID- 24109952
TI  - A graph-theoretical analysis algorithm for quantifying the transition from
      sensory input to motor output by an emotional stimulus.
AB  - Graph-theoretical analysis algorithms have been used for identifying subnetworks
      in the human brain during the Default Mode State. Here, these methods are
      expanded to determine the interaction of the sensory and the motor subnetworks
      during the performance of an approach-avoidance paradigm utilizing the
      correlation strength between the signal intensity time courses as measure of
      synchrony. From functional magnetic resonance imaging (fMRI) data of 9 healthy
      volunteers, two signal time courses, one from the primary visual cortex (sensory
      input) and one from the motor cortex (motor output) were identified and a
      correlation difference map was calculated. Graph networks were created from this
      map and visualized with spring-embedded layouts and 3D layouts in the original
      anatomical space. Functional clusters in these networks were identified with the
      MCODE clustering algorithm. Interactions between the sensory sub-network and the
      motor sub-network were quantified through the interaction strengths of these
      clusters. The percentages of interactions involving the visual cortex ranged from
      85 % to 18 % and the motor cortex ranged from 40 % to 9 %. Other regions with
      high interactions were: frontal cortex (19 +/- 18 %), insula (17 +/- 22 %),
      cuneus (16 +/- 15 %), supplementary motor area (SMA, 11 +/- 18 %) and subcortical
      regions (11 +/- 10 %). Interactions between motor cortex, SMA and visual cortex
      accounted for 12 %, between visual cortex and cuneus for 8 % and between motor
      cortex, SMA and cuneus for 6 % of all interactions. These quantitative findings
      are supported by the visual impressions from the 2D and 3D network layouts. 

PMID- 24109953
TI  - Coupling of fMRI and NIRS measurements in the study of negative BOLD response to
      intermittent photic stimulation.
AB  - Functional Magnetic Resonance Imaging (fMRI) in combination with Near Infrared
      Spectroscopy (NIRS) is finding widespread use in the analysis of brain function.
      While most of the studies deal with the detection of positive responses, here we
      focus on negative responses to visual stimulation. In a group fMRI study on
      Intermittent Photic Stimulation (IPS) we detected a sustained Negative BOLD
      Response (NBR) in the extrastriate visual cortex. To confirm and better
      characterize NBR, we repeated the same protocol during NIRS recordings. In this
      paper we show fMRI results and demonstrate the NBR on the basis of NIRS findings.

PMID- 24109954
TI  - An algorithm for determination of rank and degree of contribution of sMRI
      volumetric features in depression detection.
AB  - Brain volume changes at structural level appear to have utmost importance in
      depression biomarkers studies. However, these brain volumetric findings have very
      minimal utilization in depression detection studies at individual level. Thus,
      this paper presents an evaluation of volumetric features to identify the
      relevant/optimal features for the detection of depression. An algorithm is
      presented for determination of rank and degree of contribution (DoC) of
      structural magnetic resonance imaging (sMRI) volumetric features. The algorithm
      is based on the frequencies of each feature contribution toward the desired
      accuracy limit. Forty-four volumetric features from various brain regions were
      adopted for evaluation. From DoC analysis, the DoC of each volumetric feature for
      depression detection is calculated and the features that dominate the
      contribution are determined. 

PMID- 24109955
TI  - Structural connectivity analysis reveals topological aberrations in patients with
      schizophrenia.
AB  - Topological analysis and the associated parameters allow elucidation of brain
      networks in health and illness. Evidently useful measures for defining network
      competency such as small-worldness can potentially improve understanding of brain
      connectivity and their disruptions underlying neuropsychiatric conditions such as
      schizophrenia. In the current study, we assessed the structural differences of
      brain networks in schizophrenia patients as compared with healthy controls. As
      proof of concept investigation, diffusion tensor imaging recordings from 2
      schizophrenia patients and 2, gender and age matched, control subjects were
      subjected to analysis using several graph network distance metrics. Among them,
      those that appeared to have the ability to encode and highest sensitivity in
      shedding light about anatomical changes in neuron deficiency were the shortest
      path length and clustering coefficient parameters. Schizophrenia patients
      displayed comparatively lower clustering coefficient, longer path lengths and
      hence reduced small-worldness. These results suggest aberrant topological
      architecture in the structural brain networks of patients with schizophrenia,
      which may impact the psychopathological and cognitive manifestations of this
      potentially crippling illness. 

PMID- 24109956
TI  - Fundamental study on micro calcification detection using twinkling sign (TS): the
      effect of stiffness of surrounding tissue on the appearance of TS.
AB  - The twinkling sign (TS) observed in ultrasound imaging (e.g., color flow mode and
      pulse Doppler mode) has been reported in previous researches as a potential
      phenomenon to detect micro calcification in soft tissue. However, the mechanism
      of the twinkling sign has not been clearly understood yet. The authors
      investigated the effect of stiffness of surrounding tissue on the appearance of
      TS using the soft tissue-mimicking phantoms and a medical ultrasound device. The
      author used Poly (vinyl alcohol) hydro (PVA-H) gel as the material of phantom and
      developed three phantoms with different PVA concentration; 8 %wt, 10 %wt and 15
      %wt those correspond to Young's modulus (E) as 50 kPa, 100 kPa and 230 kPa,
      respectively. Micro glass and CaCO3 particles were embedded in the phantoms as
      pseudo micro calcification. The authors observed TS in each phantom and analyzed
      the temporal average of TS. The temporal average of TS was largest in the 8 %wt
      (E = 50 kPa) PVA-H gel phantom, and decreased with increasing the phantom
      stiffness. The result indicated that the micro oscillation of the particles had a
      close relationship with the occurrence of TS.

PMID- 24109957
TI  - Virtual navigator 3D panoramic for breast examination.
AB  - Breast examination both for screening and second level of investigation has
      spread worldwide, due to increased breast cancer awareness. Thus, different
      diagnostic imaging technologies emerged in breast application. Ultrasound (US), a
      real-time examination, non-invasive, cost effective, ideal also for repetitive
      follow-up and able to give information about anatomy, hemodynamics and tissue
      stiffness, plays an important role in breast diagnostics. The present work
      describes the innovative three-dimensional (3D) Panoramic (Pan) tool of Virtual
      Navigator technology for real-time fusion imaging of breast 3D US volumes with bi
      dimensional US scans. A Motion Control Sensor enables the correction of the
      examined subject's movements. Data about fusion precision and system performances
      will be presented regarding tests in vitro, in ex-vivo and in vivo. 

PMID- 24109958
TI  - Real-time high-resolution vascular ultrasound using frequency domain
      interferometry with the ROI-division process.
AB  - We have proposed a high-range-resolution ultrasound imaging method for human
      carotid artery using an adaptive beamforming technique based on frequency domain
      interferometry (FDI). The method assumes that the received signal consists of
      multiple echoes of targets and noise, where the waveform of each echo is similar
      to that of the reference signal. In this study, we examine the dependence of the
      echo waveform on the target depth, and investigate the proper measurement-range
      for the FDI imaging method using a reference signal. Furthermore, we propose a
      ROI-division process, where each sub-ROI has a proper measurement-range for the
      application of the FDI imaging method. Simulation and experimental results show
      the efficiency of the ROI-division process in improving the image quality of
      human carotid artery acquired using the FDI imaging method. We believe that the
      modified FDI imaging method with the ROI-division process has the potential to
      facilitate significant progress in the detection of vessel stenosis and in the
      assessment of cardiovascular disease risk. 

PMID- 24109959
TI  - Aortic valve segmentation from ultrasound images based on shape constraint CV
      model.
AB  - Image Guided Intervention for valvular heart disease is increasingly making
      progress in minimally invasive manner, where effective and accurate segmentation
      of aortic valve (AV) from echocardiography is fundamental to improve the intra
      operative location accuracy. This paper proposes a shape constraint Chan-Vese
      (CV) model for segmenting the AV from ultrasound (US) images. Considering the
      poor quality and speckle noise in AV US images, the problem of the overflow at
      the weak edge is solved by adding the shape constraint to the CV model. The
      predefined shape constructed from AV region is applied as an energy constraint to
      the energy function through a signed distance map, and the AV is detected from
      the US image by minimizing the energy function. A hundred AV segmentation results
      are analyzed in the experiment, where the evaluation parameters are 95.38 +/-
      2.7%, 1.4 +/- 0.5 mm, 2.07 +/- 1.3 mm in transthoracic AV and 97.21 +/- 1.6%, 0.7
      +/- 0.15 mm, 1.04 +/- 0.6 mm in transesophageal AV, which reveal that the shape
      constraint CV model can segment AV accurately, efficiently and robustly.

PMID- 24109960
TI  - Virtual navigator real-time ultrasound fusion imaging with positron emission
      tomography for liver interventions.
AB  - Real-time fusion imaging technologies are increasingly being used among
      interventional radiologists, mostly Computed Tomography (CT) or Magnetic
      Resonance Imaging (MRI) dataset, fused with Ultrasound (US) imaging. In addition,
      fusion of Positron Emission Tomography (PET) and CT is increasingly diffused in
      clinical practice, due to the wide availability of PET scanners and the
      capability to make either a direct (acquisitions performed within the same
      system) or an indirect (procedure performed on an external workstation, merging
      the two different sets of acquired data) fusion with CT data. The present work
      describes the feasibility of real-time fusion imaging directly between PET data
      and US imaging, with CT scans being used only for PET-US fusion registration.
      Data on multimodality registration precision and clinical applications are
      presented as well. 

PMID- 24109961
TI  - Ultrasound image-based endoscope localization for minimally invasive fetoscopic
      surgery.
AB  - The purpose of this work is to introduce an ultrasound image-based intraoperative
      scheme for rigid endoscope localization during minimally invasive fetoscopic
      surgery. Positional information of surgical instruments with respect to
      anatomical features is important for the development of computer-aided surgery
      applications. While most surgical navigation systems use optical tracking systems
      with satisfactory accuracy, there are several operation limitations in such
      systems. We propose an elegant framework for intraoperative instrument
      localization that does not require any external tracking system but uses an
      ultrasound imaging system and a computation scheme based on constrained
      kinematics of minimally invasive fetoscopic surgery. Our proposed algorithm
      simultaneously estimates endoscope and port positions in an online sequential
      fashion with standard deviation of 1.28 mm for port estimation. Robustness of the
      port estimation algorithm against external disturbance was demonstrated by
      intentionally introducing artificial errors to measurement data. The estimation
      converges within eight iterations under disturbance magnitude of 30 mm. 

PMID- 24109962
TI  - Dual-band multi-aperture enhanced redox imaging of colonic adenomas for
      endoscopes with a high-performance CMOS imager.
AB  - Dual-band multi-aperture imaging of colonic adenomas based on the redox condition
      of mucosal cells for next-generation endoscopes is proposed. A low-noise and high
      dynamic-range CMOS imager with the folding integration and the cyclic ADC is
      utilized in the single-imager multi-aperture camera system with 475-nm and 530-nm
      band-pass filters. A redox image is calculated from four kinds of images, 475-nm
      and 530-nm fluorescence images for 365-nm and 405-nm excitation lights. Dark
      current and random noise are reduced with a selective averaging method. The
      contrast of the redox image has been successfully enhanced. 

PMID- 24109963
TI  - Development of dual-color simultaneous single molecule imaging system for
      analyzing multiple intracellular trafficking activities.
AB  - Intracellular trafficking is a critical process for cell physiology. Previous
      extensive studies employing biochemical and molecular biological approaches have
      provided qualitative information about intracellular trafficking, but we have
      little quantitative information due to technical limitations of these assays. We
      therefore developed a novel method for quantifying intracellular trafficking
      based on single molecule imaging with Quantum dot (QD) fluorescent nanocrystals
      and quantitatively described the trafficking properties of some recycling
      proteins. We herein first describe how to label intracellular molecules with QD
      which has no cell permeability and how to quantify intracellular trafficking, and
      then we detail the development of a novel experimental system allowing multi
      color simultaneous single molecule imaging for analyzing the relationships of
      intracellular trafficking activities among multiple molecules having distinct
      trafficking properties. Finally, we document how we confirmed the reliability of
      our system by simultaneously analyzing the intracellular movements of two
      recycling protein, GLUT4 glucose transporter and transferrin receptor. Since
      impairment of intracellular trafficking has critical etiological roles in various
      late-onset diseases such as type 2 diabetes, our novel imaging system may be a
      powerful tool for developing next-generation biomedical devices for diagnostics
      and medical treatment based on intracellular trafficking. 

PMID- 24109964
TI  - A real-time spectral mapper as an emerging diagnostic technology in biomedical
      sciences.
AB  - Real time spectral imaging and mapping at video rates can have tremendous impact
      not only on diagnostic sciences but also on fundamental physiological problems.
      We report the first real-time spectral mapper based on the combination of snap
      shot spectral imaging and spectral estimation algorithms. Performance evaluation
      revealed that six band imaging combined with the Wiener algorithm provided high
      estimation accuracy, with error levels lying within the experimental noise. High
      accuracy is accompanied with much faster, by 3 orders of magnitude, spectral
      mapping, as compared with scanning spectral systems. This new technology is
      intended to enable spectral mapping at nearly video rates in all kinds of dynamic
      bio-optical effects as well as in applications where the target-probe relative
      position is randomly and fast changing. 

PMID- 24109965
TI  - Automated localization of cysts in diabetic macular edema using optical coherence
      tomography images.
AB  - This paper presents a novel automated system that localizes cysts in optical
      coherence tomography (OCT) images of patients with diabetic macular edema (DME).
      First, in each image, six sub-retinal layers are detected using an iterative high
      pass filtering approach. Next, significantly dark regions within the retinal
      micro-structure are detected as candidate cystoid regions. Each candidate cystoid
      region is then further analyzed using solidity, mean and maximum pixel value of
      the negative OCT image as decisive features for estimating the area of cystoid
      regions. The proposed system achieves 90% correlation between the estimated
      cystoid area and the manually marked area, and a mean error of 4.6%. Finally the
      proposed algorithm locates the cysts in the inner plexiform region, inner nuclear
      region and outer nuclear region with an accuracy of 88%, 86% and 80%,
      respectively. 

PMID- 24109966
TI  - Fully automated calcium detection using optical coherence tomography.
AB  - Optical Coherence Tomography (OCT) is a new invasive technology for performing
      high-resolution cross-sectional imaging of the coronary arteries. In OCT images
      only Calcified plaque (CA) components can be accurately depicted as light
      penetrates hard tissue. In this work we present an automated method for detecting
      CA in OCT images. The method is fully automated as no user intervention is needed
      and includes three steps. In the first step the region between the lumen and the
      maximum penetration depth of OCT from the lumen border is determined. In the
      second step the region is classified into 3 clusters using the K-means algorithm.
      CA is identified using the results of k-means. The method was validated using
      experts' annotations on 27 images. The sensitivity of the method is 83% with
      Positive predictive value (PVV) 74 %.

PMID- 24109967
TI  - A novel edge tracking approach for cornea in optical coherence tomography
      anterior chamber images.
AB  - A new edge tracking method for cornea in optical coherence tomography anterior
      chamber images has been proposed in the paper. The new approach detects the edge
      of cornea outside the cornea first. Then, it fixes the detected edge, which
      follows the future knowledge of cornea, to make sure that only the real edge of
      cornea could be left. Finally, the method fits the fixed edge by fourth order
      least squares. The advantage of this proposed method is that it could fit the
      edge of cornea even for abnormal corneas. 

PMID- 24109968
TI  - Raman molecular fingerprint of non-structural protein 1 in phosphate buffer
      saline with gold substrate.
AB  - SERS is a form of Raman spectroscopy that is enhanced with nano-sensing chip as
      substrate. It can yield distinct biochemical fingerprint for molecule of solids,
      liquids and gases. Vice versa, it can be used to identify unknown molecule. It
      has further advantage of being non-invasive, non-contact and cheap, as compared
      to other existing laboratory based techniques. NS1 has been clinically accepted
      as an alternative biomarker to IgM in diagnosing viral diseases carried by virus
      of flaviviridae. Its presence in the blood serum at febrile stage of the
      flavivirus infection has been proven. Being an antigen, it allows early detection
      that can help to reduce the mortality rate. This paper proposes SERS as a
      technique for detection of NS1 from its scattering spectrum. Contribution from
      our work so far has never been reported. From our experiments, it is found that
      NS1 protein is Raman active. Its spectrum exhibits five prominent peaks at Raman
      shift of 548, 1012, 1180, 1540 and 1650 cm(-1). Of these, peak at 1012 cm(-1)
      scales the highest intensity. It is singled out as the peak to fingerprint the
      NS1 protein. This is because its presence is verified by the ring breathing
      vibration of the benzene ring structure side chain molecule. The characteristic
      peak is found to vary in proportion to concentration. It is found that for a 99%
      change in concentration, a 96.7% change in intensity is incurred. This yields a
      high sensitivity of about one a.u. per ppm. Further investigation from the
      characterization graph shows a correlation coefficient of 0.9978 and a standard
      error estimation of 0.02782, which strongly suggests a linear relationship
      between the concentration and characteristic peak intensity of NS1. Our finding
      produces favorable evidence to the use of SERS technique for detection of NS1
      protein for early detection of flavivirus infected diseases with gold substrate.

PMID- 24109969
TI  - Magnetic field effects on mitochondrion-activity-related optical properties in
      slime mold and bone forming cells.
AB  - In the present study, a cellular level response of Cyto-aa3 oxidation was
      investigated in real time under both time-varying and strong static magnetic
      fields of 5 T. Two kinds of cells, a slime mold, Physarum polycephalum, and bone
      forming cells, MC-3T3-E1, were used for the experiments. The oxidation level of
      the Cyto-aa3 was calculated by optical absorptions at 690 nm, 780 nm and 830 nm.
      The sample, fiber-optics and an additional optical fiber for light stimulation
      were set in a solenoidal coil or the bore of a 5-T superconducting magnet. The
      solenoidal coil for time-varying magnetic fields produced sinusoidal magnetic
      fields of 6 mT. The slime mold showed a periodic change in Cyto-aa3 oxidation,
      and the oxidation-reduction cycle of Cyto-aa3 was apparently changed when visible
      light irradiated the slime mold. Similarly to the case with light, time-varying
      magnetic stimulations changed the oxidation-reduction cycle during and after the
      stimulation for 10 minutes. The same phenomena were observed in the MC-3T3-E1
      cell assembly, although their cycle rhythm was comparatively random. Finally,
      magnetic field exposure of up to 5 T exhibited a distinct suppression of Cyto-aa3
      oscillation in the bone forming cells. Exposure up to 5 T was repeated five
      times, and the change in Cyto-aa3 oxidation reproducibly occurred.

PMID- 24109970
TI  - A novel single compartment in vitro model: Perflurocarbons for
      electrophysiological studies of the rat urinary bladder.
AB  - This study presents a novel single compartment model for in vitro
      electrophysiological studies of the rat urinary bladder. We tested the
      functionality and suitability of FC-770 (a Perflurocarbon) for in vitro recording
      of nerve activity arising from the bladder in a single compartment setup. We have
      also favorably tested stimulation of the bladder via the bladder nerves in FC
      770. The organ viability was monitored by recording spontaneous contractions of
      the bladder for a certain time. We propose the use of FC-770 as a fluid for nerve
      recording/stimulation in vitro as well as for maintaining organ viability, over
      the commonly used two compartmental methods. 

PMID- 24109971
TI  - A necklace sonar with adjustable scope range for assisting the visually impaired.
AB  - A sonar based device with tactile feedback was developed to improve the mobility
      and independence of visually impaired individuals. It features a
      transceiver/receiver, a potentiometer, a microcontroller, a rechargeable polymer
      lithium ion battery, and a Nokia Cell phone vibrator. All components are
      commercially available and housed in a custom acrylic package with 86 mm * 34 mm
      * 12 mm in dimension, and 120 grms in weight. Additionally, the device features
      an adjustable detection scheme for user customization of distance range, and a
      tactile feedback system that avoids interference with auditory sensory
      information. The device was tested for its navigational efficacy in an artificial
      indoor environment, and in a live outdoor setting. Ten subjects (9 males and 1
      female), with a mean age of 35 years-old (range: 17 to 52) were presented with a
      series of navigational tasks resulting in considerable reduction of head,
      shoulder, chest, and arms collisions during their locomotion. We conclude that
      this device greatly improves the mobility and safety of visually impaired
      individuals. 

PMID- 24109972
TI  - Sub-threshold standard cell library design for ultra-low power biomedical
      applications.
AB  - Portable/Implantable biomedical applications usually exhibit stringent power
      budgets for prolonging battery life time, but loose operating frequency
      requirements due to small bio-signal bandwidths, typically below a few kHz. The
      use of sub-threshold digital circuits is ideal in such scenario to achieve
      optimized power/speed tradeoffs. This paper discusses the design of a sub
      threshold standard cell library using a standard 0.18-um CMOS technology. A
      complete library of 56 standard cells is designed and the methodology is ensured
      through schematic design, transistor width scaling and layout design, as well as
      timing, power and functionality characterization. Performance comparison between
      our sub-threshold standard cell library and a commercial standard cell library
      using a 5-stage ring oscillator and an ECG designated FIR filter is performed.
      Simulation results show that our library achieves a total power saving of 95.62%
      and a leakage power reduction of 97.54% when compared with the same design
      implemented by the commercial standard cell library (SCL). 

PMID- 24109973
TI  - A wireless energy transfer platform, integrated at the bedside.
AB  - This paper presents the design of a wireless energy transfer platform, integrated
      at the bedside. The system contains a matrix of identical inductive power
      transmitters, which are optimised to provide power to a wearable sensor network,
      with the purpose of wirelessly recording vital signals over an extended period of
      time. The magnetic link, operates at a transfer frequency of 6.78MHz and is able
      to transfer a power of 3.3mW to the remote side at an inter-coil distance of
      100mm. The total efficiency of the power link is 26%. Moreover, the platform is
      able to dynamically determine the position of freely moving sensor nodes and
      selectively induce a magnetic field in the area where the sensor nodes are
      positioned. As a result, the patient will not be subjected to unnecessary
      radiation and the specific absorption rate standards are met more easily. 

PMID- 24109974
TI  - Glucose detection in human sweat using an electronic nose.
AB  - In the last years attempts to develop a non-invasive glucose system based on the
      glucose levels in sweat have been studied. In this paper, 32 metal oxide
      semiconductor (MOS) sensors operating at different temperatures have been used to
      develop a multisensor olfactory system that allows to study the glucose levels in
      sweat. In order to develop repeatable experiments, artificial sweat at different
      glucose concentrations were developed in the laboratory. The obtained results
      suggest high viability of the approach. Although, the sensitivity of the sensors
      system needs to be improved. 

PMID- 24109975
TI  - Investigating the impact of force and movements on impedance magnitude and EEG.
AB  - The success of applying dry sensor technology in measuring electroencephalogram
      (EEG) signals will have a significant impact on a wider adoption of brain
      activity monitoring in ambulatory as well as real life solutions. The presence of
      motion artifacts is the major obstacle in applying dry sensors for long-term EEG
      monitoring. In this paper we assess the impact of external forces applied on a
      dry EEG electrode as well as the impact of head and body movements on the
      electrode-tissue contact impedance and the EEG signal. The data collection method
      and the preliminary correlation analysis are presented. The analysis demonstrates
      that the impedance magnitude and EEG changes are highly correlated when artifacts
      are induced by the application of force or head and body movements, only in case
      these artifacts are short (less than 3s) and exhibit regular pattern. The
      correlation between the EEG and impedance magnitude is lower for longer artifact
      segments, especially the ones containing artifacts with irregular movements or
      large variations in the applied force. This indicates a time-dependent, non
      linear relation between the artifact-related phenomena, impedance magnitude, and
      EEG. 

PMID- 24109976
TI  - Kinect-based system for automated control of terrestrial insect biobots.
AB  - Centimeter scale mobile biobots offer unique advantages in uncertain
      environments. Our previous experimentation has demonstrated neural stimulation
      techniques in order to control the motion of Madagascar hissing cockroaches.
      These trials relied on stimulation by a human operator using a remote control. We
      have developed a Kinect-based system for computer operated automatic control of
      cockroaches. Using image processing techniques and a radio transmitter, this
      platform both detects the position of the roach biobot and sends stimulation
      commands to an implanted microcontroller-based receiver. The work presented here
      enables repeatable experimentation and allows precise quantification of the line
      following capabilities of the roach biobot. This system will help refine our
      model for the stimulation response of the insect and improve our ability to
      direct them in increasingly dynamic situations. 

PMID- 24109977
TI  - An ultra-low power (ULP) bandage-type ECG sensor for efficient cardiac disease
      management.
AB  - This paper proposed an ultra-low power bandage-type ECG sensor (the size: 76 * 34
      * 3 (mm(3)) and the power consumption: 1 mW) which allows for a continuous and
      real-time monitoring of a user's ECG signals over 24h during daily activities.
      For its compact size and lower power consumption, we designed the analog front
      end, the SRP (Samsung Reconfigurable Processor) based DSP of 30 uW/MHz, and the
      ULP wireless RF of 1 nJ/bit. Also, to tackle motion artifacts(MA), a MA
      monitoring technique based on the HCP (Half-cell Potential) is proposed which
      resulted in the high correlation between the MA and the HCP, the correlation
      coefficient of 0.75 +/- 0.18. To assess its feasibility and validity as a
      wearable health monitor, we performed the comparison of two ECG signals recorded
      form it and a conventional Holter device. As a result, the performance of the
      former is a little lower as compared with the latter, although showing no
      statistical significant difference (the quality of the signal: 94.3% vs 99.4%;
      the accuracy of arrhythmia detection: 93.7% vs 98.7%). With those results, it has
      been confirmed that it can be used as a wearable health monitor due to its
      comfortability, its long operation lifetime and the good quality of the measured
      ECG signal.

PMID- 24109978
TI  - Characterization of dry biopotential electrodes.
AB  - Driven by the increased interest in wearable long-term healthcare monitoring
      systems, varieties of dry electrodes are proposed based on different materials
      with different patterns and structures. Most of the studies reported in the
      literature focus on proposing new electrodes and comparing its performance with
      commercial electrodes. Few papers are about detailed comparison among different
      dry electrodes. In this paper, printed metal-plate electrodes, textile based
      electrodes, and spiked electrodes are for the first time evaluated and compared
      under the same experimental setup. The contact impedance and noise
      characterization are measured. The in-vivo electrocardiogram (ECG) measurement is
      applied to evaluate the overall performance of different electrodes. Textile
      electrodes and printed electrodes gain comparable high-quality ECG signals. The
      ECG signal obtained by spiked electrodes is noisier. However, a clear ECG
      envelope can be observed and the signal quality can be easily improved by backend
      signal processing. The features of each type of electrodes are analyzed and the
      suitable application scenario is addressed. 

PMID- 24109979
TI  - Preamplifiers for non-contact capacitive biopotential measurements.
AB  - Non-contact biopotential sensing is an attractive measurement strategy for a
      number of health monitoring applications, primarily the ECG and the EEG. In all
      such applications a key technical challenge is the design of a low-noise trans
      impedance preamplifier for the typically low-capacitance, high source impedance
      sensing electrodes. In this paper, we compare voltage and charge amplifier
      designs in terms of their common mode rejection ratio, noise performance, and
      frequency response. Both amplifier types employ the same operational
      transconductance amplifier (OTA), which was fabricated in a 0.35 um CMOS process.
      The results show that a charge amplifier configuration has advantages for small
      electrode-to-subject coupling capacitance values (less than 10 pF--typical of
      noncontact electrodes) and that the voltage amplifier configuration has
      advantages for electrode capacitances above 10 pF.

PMID- 24109980
TI  - Toward improving the Laplacian estimation with novel multipolar concentric ring
      electrodes.
AB  - Conventional electroencephalography with disc electrodes has major drawbacks
      including poor spatial resolution, selectivity and low signal-to-noise ratio that
      are critically limiting its use. Concentric ring electrodes are a promising
      alternative with potential to improve all of the aforementioned aspects
      significantly. In our previous work, the tripolar concentric ring electrode was
      successfully used in a wide range of applications demonstrating its superiority
      to conventional disc electrode, in particular, in accuracy of Laplacian
      estimation. This paper takes the first fundamental step toward further improving
      the Laplacian estimation of the novel multipolar concentric ring electrodes by
      proposing a general approach to estimation of the Laplacian for an (n + 1)-polar
      electrode with n rings using the (4n + 1)-point method for n >= 2 that allows
      cancellation of all the truncation terms up to the order of 2n. Examples of using
      the proposed approach to estimate the Laplacian for the cases of tripolar and,
      for the first time, quadripolar concentric ring electrode are presented. 

PMID- 24109981
TI  - Sparse generalized canonical correlation analysis for biological model
      integration: a genetic study of psychiatric disorders.
AB  - In the post-genomic era, unveiling causal traits in the complex mechanisms that
      involve a number of diseases has been highlighted as one of the key goals. Much
      research has recently suggested integrative approaches of both genomewide
      association studies (GWAS) and gene expression profiling-based studies provide
      greater insight of the mechanism than utilizing only one. In this paper, we
      propose a novel method, sparse generalized canonical correlation analysis
      (SGCCA), to integrate multiple biological data such as genetic markers, gene
      expressions, and disease phenotypes. The proposed method provides a powerful
      approach to comprehensively analyze complex biological mechanism while utilizing
      the multiple data simultaneously. The new method is also designed to identify a
      few of the elements significantly involved in the system among a large number of
      elements within the variable sets. The advantage of the method as well lies in
      the output of easily interpretable solutions. To verify the performance of SGCCA,
      we performed experiments with simulation data and human brain data of psychiatric
      diseases. Its capability to detect significant elements of the sets and the
      relations of the complex system is assessed. 

PMID- 24109982
TI  - Code generator for distributed parameter biological model simulation with PDE
      numerical schemes.
AB  - The physiological simulation at the tissue and organ level typically involves the
      handling of partial differential equations (PDEs). Boundary conditions and in
      cases like pharmacokinetics, distributed parameters add to the complexity of the
      PDE solution. These factors make most PDE solutions and their corresponding
      program codes tailored for specific problems. We propose a general approach for
      handling PDEs in computational models using a replacement scheme for
      discretization. This method allows for the handling of the different PDE types.
      The replacement scheme involves substituting all the partial differential terms
      with the numerical solution equations. Once the model equations are discretized
      with the numerical solution scheme, instances of the equations are generated to
      undergo dependency analysis. The result of the dependency analysis is then used
      to determine the simulation loop structure and generate the program code. 

PMID- 24109983
TI  - Analysis of selective constraints on mitochondrial DNA, flight ability and
      physiological index on avian.
AB  - For most of the birds in the word, they can be divided into two main groups, i.e.
      resident birds and migratory ones. Most of the energy required for long-distance
      migration is supplied by mitochondria via oxidative phosphorylation. Therefore,
      the evolutionary constraints acted on the mitochondria DNA (mtDNA) are considered
      to vary with the locomotive abilities and flight speed. The flight speed is
      assumed to increase with mass and wing loading according to the fundamental
      aerodynamic theories, which is common between aves and aircrafts. We compared 148
      avian mitochondrial genomes and main physiological parameters. More nonsynonymous
      nucleotide substitutions than synonymous ones are accumulated in low-speed and
      flightless birds rather than high-speed flying birds. No matter how the speed is
      obtained, directly measured or estimated through physiological index. Our results
      demonstrated that, besides artificial and environmental factors, selective
      constraints relevant to flight ability play an essential role in the evolution of
      mtDNA, even it might cause the extinction of avian species. 

PMID- 24109984
TI  - GOseek: a gene ontology search engine using enhanced keywords.
AB  - We propose in this paper a biological search engine called GOseek, which
      overcomes the limitation of current gene similarity tools. Given a set of genes,
      GOseek returns the most significant genes that are semantically related to the
      given genes. These returned genes are usually annotated to one of the Lowest
      Common Ancestors (LCA) of the Gene Ontology (GO) terms annotating the given
      genes. Most genes have several annotation GO terms. Therefore, there may be more
      than one LCA for the GO terms annotating the given genes. The LCA annotating the
      genes that are most semantically related to the given gene is the one that
      receives the most aggregate semantic contribution from the GO terms annotating
      the given genes. To identify this LCA, GOseek quantifies the contribution of the
      GO terms annotating the given genes to the semantics of their LCAs. That is, it
      encodes the semantic contribution into a numeric format. GOseek uses microarray
      experiment data to rank result genes based on their significance. We evaluated
      GOseek experimentally and compared it with a comparable gene prediction tool.
      Results showed marked improvement over the tool. 

PMID- 24109985
TI  - Modeling of change in blood volume and extracellular fluid volume during
      hemodialysis.
AB  - Knowledge of dynamics of shift of fluid volume between intra- and extravascular
      compartments during hemodialysis (HD) is important for managing HD treatment to
      help patients approach dry weight without hypotension. The Relative blood volume
      (RBV) monitor indicates change in plasma volume based on the difference between
      ultrafiltration rate (UFR) and plasma refilling rate (PRR) during HD. However,
      the absolute value of PRR cannot be obtained from RBV. The aim of this study was
      to investigate whether fluid transport from the interstitial to blood spaces can
      be quantitatively analyzed with a two compartments model. 14 patients (30
      measurements) were studied. RBV using a blood volume monitor (BVM, Fresenius) and
      calf extracellular volumes (ECV) by calf bioimpedance device (Hydra 4200, Xitron)
      were continuously measured during HD. A mathematic model was established with
      unknown transport coefficients (k1, k2, alpha, beta, gamma, delta) and these
      coefficients were estimated using a Least Squares Optimization algorithm by
      fitting from experimental data. A high correlation (R(2)>0.8) between
      experimental data and calculation by the model were observed in both RBV and ECV
      measurements. Coefficients k1 and delta significantly differed with different
      degree of hydration. This model provides parameters which can used to understand
      relationships between degree of hydration and refilling rate. 

PMID- 24109986
TI  - A high performance cloud computing platform for mRNA analysis.
AB  - Multiclass classification is an important technique to many complex
      bioinformatics problems. However, their performance is limited by the computation
      power. Based on the Apache Hadoop design framework, this study proposes a two
      layer architecture that exploits the inherent parallelism of GA-SVM
      classification to speed up the work. The performance evaluations on an mRNA
      benchmark cancer dataset have reduced 86.55% features and raised accuracy from
      97.53% to 98.03%. With a user-friendly web interface, the system provides
      researchers an easy way to investigate the unrevealed secrets in the fast-growing
      repository of bioinformatics data. 

PMID- 24109987
TI  - Stochastic pacing effect on cardiac alternans--simulation study of a 2D human
      ventricular tissue.
AB  - The physiological heart rate is not deterministic but rather varies in time;
      those variations are termed heart rate variability (HRV). It is well known that
      low HRV is often seen in patients prone to arrhythmias. The ability of HRV to
      predict arrhythmia events is traditionally attributed to an impaired balance
      between the autonomic sympathetic and parasympathetic tone. However, there is no
      concrete model that directly relates low HRV to the electrical conduction in the
      cardiac tissue and to arrhythmogenic dynamic properties. We simulated stochastic
      cardiac pacing with Gaussian distribution using 2D human ventricular tissue
      model. Conduction stabilization was obtained with stochastic pacing owing to
      reduced propensity of the appearance of action potential duration (APD)
      discordant alternans and reduced APD spatial heterogeneity. 

PMID- 24109988
TI  - Modeling atrial pacing.
AB  - We present a model-based study of a therapeutical approach to atrial fibrillation
      based on pacing. After a systematic evaluation of different atrial pacing sites,
      we selected pacing from the septum area and designed a novel septum pacing
      protocol for atrial fibrillation termination. We then evaluated the performance
      of septum pacing in different models of atrial fibrillation and investigated the
      effect atrial substrate (cellular properties, anisotropy and heterogeneities) on
      the ability to capture during pacing. This study highlights the need for the
      development of patient-specific algorithms for atrial therapies. 

PMID- 24109989
TI  - A patient-specific model of virtual ablation for atrial fibrillation.
AB  - The purpose of this study was to propose a patient-specific model of atrial
      fibrillation (AF) and apply it to virtual radiofrequency ablation (RFA). We
      obtained patient-specific geometries of the left atrium (LA) from CT data and
      constructed three-dimensional (3D) simulation models. A bidomain Courtemanche
      model was used to simulate the 3D electric waves on the LA surface, and an S1-S2
      protocol was applied to induce AF in the model. To identify scar areas in the
      models, we converted clinically measured voltage data on the LA surface to the
      scar maps of the simulation model. Then, after initiation of AF, we applied the
      virtual ablation scheme to the model and investigated whether the AF was
      terminated by the scheme. The computed results of AF and ablation were similar to
      those of clinical observation, providing a clinically important simulation method
      for preclinical virtual trials of AF treatment. 

PMID- 24109990
TI  - Models of ventricular arrhythmia mechanisms.
AB  - The mechanisms that initiate and sustain ventricular arrhythmias in the human
      heart are clinically important, but hard to study experimentally. In this study,
      a monodomain model of electrical activation was used to examine how dynamics of
      electrophysiology at the cell scale influence the surface activation patterns of
      VF at the tissue scale. Cellular electrophysiology was described with two
      variants of a phenomenological model of the human ventricular epicardial action
      potential. The tissue geometry was an 8.0 * 8.0 * 1.2 cm 3D tissue slab with
      axially symmetric anisotropy. In both cases an initial re-entrant wave fragmented
      into multiple wavelets of activation. The model variant with steep action
      potential duration restitution produced much more complex activation, with a
      greater average number of filaments (13.79) than the variant with less steep
      restitution (3.08). More complex activation was associated with proportionally
      fewer transmural filaments, and so the average number of epicardial wavefronts
      and phase singularities per filament was lower. The average number of epicardial
      phase singularities and wavefronts for the model variant with less steep
      restitution were consistent with experimental observations in the human heart.
      This study shows that small changes in cell scale dynamics can have a large
      influence on the complexity of re-entrant activation in simulated 3D tissue, as
      well as on the features observed on the epicardial surface.

PMID- 24109991
TI  - A bilayer representation of the human atria.
AB  - Atrial fibrillation is the most commonly encountered clinical arrhythmia. Despite
      recent advances in treatment by catheter ablation, its origin is still
      incompletely understood and it may be difficult to treat. Computer modelling
      offers an attractive complement to experiment. Simulations of fibrillation,
      however, are computationally demanding since the phenomenon requires long periods
      of observation. Because the atria are thin walled structures, they are often
      modelled as surfaces. However, this may not always be appropriate as the crista
      terminalis and pectinate muscles are discrete fibrous structures lying on the
      endocardium and cannot be incorporated into the surface. In the left atrium,
      there are essentially two layers with an abrupt change in fibre orientation
      between them. We propose a double layer method, using shell elements to
      incorporate wall thickness, where fibre direction is independent in each layer
      and layers are electrically linked. Starting from human multi-detector CT (MDCT)
      images, we extracted surfaces for the atria and manually added a coronary sinus.
      Propagation of electrical activity was modelled with the monodomain equation.
      Results indicate that major features are retained while reducing computation cost
      considerably. Meshes based on the two layer approach will facilitate studies of
      AF. 

PMID- 24109992
TI  - Parametrization strategies for matching activation sequences in models of
      ventricular electrophysiology.
AB  - Driven by recent advances in medical imaging, image segmentation and numerical
      techniques computer models of ventricular electrophysiology account for
      increasingly finer levels of anatomical and biophysical detail. However,
      considering the large number of model parameters involved parametrization poses a
      major challenge. A minimum requirement in combined experimental and modeling
      studies which aim at making specific predictions on a case by case basis is to
      achieve good agreement in activation and repolarization sequences between model
      and experiment or patient data. In this study we propose basic techniques which
      aide in determining bidomain parameters to match ventricular activation
      sequences. Two specific aspects will be considered. First, conduction velocity in
      the ventricles is orthotropic and varies in space. An iterative parametrization
      algorithm is implemented which determines appropriate conductivities which yield
      prescribed velocities. Secondly, impulse propagation in the ventricles is
      initiated subendocardially at Purkinje-ventricular junctions, the terminal
      endings of Purkinje system (PS), and, thus, the PS plays a key role in
      determining the shape of activation wave fronts as reflected in the QRS complex
      of the electro-cardiogram (ECG). While ventricular models equipped with generic
      PS topologies match well with experimental observation in terms of epicardial
      breakthrough sites, predicted ECGs match poorly with known key ECG
      characteristics. 

PMID- 24109993
TI  - Population activity in auditory cortex of the awake rat revealed by recording
      with dense microelectrode array.
AB  - Cortical mechanisms of auditory perception include temporal interaction between
      neuronal ensembles in a functional cortical structure such as a place code of
      frequency, or tonotopic map. To investigate the mechanism, a recording method is
      needed to densely map spatio-temporal activity pattern within the predefined
      tonotopic organization specifically in the awake condition. The present study has
      proposed and developed an experimental system that is capable of simultaneous
      neural recording with a grid array of 100 sites with 400-um inter-electrode
      distance in the 4(th) layer of auditory cortex of awake rat. Both multiunit
      activities (MUA) and local field potentials (LFPs) confirmed the tonotopic map in
      the auditory cortex. In addition, spectral powers in higher frequency components
      (4-120 Hz) were enhanced and a lower frequency component (1-4 Hz) was reduced
      during waking. Phase synchronization between recording sites in the gamma-band
      oscillatory activity was generally smaller in the awake cortex than in the
      anesthetized cortex. These results have proven the feasibility of our recording
      and will open a new avenue to investigate neural activities in the functional map
      of awake cortex. 

PMID- 24109994
TI  - Identification and quantification of electrical leakage pathways in floating
      microelectrode arrays.
AB  - The long-term reliability of neural recording and stimulation electrode arrays is
      becoming the limiting factor for neural interfaces. For effective electrode
      design, electrical connection to the surrounding neural tissue and fluid should
      be limited to the electrode tips, with all other leakage currents minimized. It
      is the goal of this study to identify and quantify electrical leakage within
      commercially available floating microelectrode arrays (FMAs). Both short term and
      accelerated stress tests were performed on entire FMAs, as well as on individual
      electrodes typical of such arrays. Preliminary results of these tests indicate
      that leakage currents are present due to water penetration of their insulation
      layer initially, but that prolonged water exposure at high temperature may seal
      the defects that cause these currents. SEM photos taken of the electrode shafts
      show extensive defect regions that may correlate with the test data. 

PMID- 24109995
TI  - Improved chronic neural stimulation using high surface area platinum electrodes.
AB  - We report a novel nano-cluster platinum (NCPt) film that exhibits enhanced
      performance as an electrode material for neural stimulation applications. Nano
      cluster films were deposited using a custom physical vapor deposition process and
      patterned on a flexible polyimide microelectrode array using semiconductor
      processing technology. Electrode performance was characterized in vitro using
      electrochemical impedance spectroscopy and compared with sputtered thinfilm
      platinum (TFPt) electrodes. We characterized electrode impedance, charge storage
      capacity, voltage transient properties, and relative surface area enhancement in
      vitro. Preliminary lifetime testing of the electrode reveals that the NCPt
      electrodes degrade more slowly than TFPt electrodes. The combination of material
      biocompatibility, electrochemical performance, and preliminary lifetime results
      point to a promising new electrode material for neural interface devices. 

PMID- 24109996
TI  - Ultra-compliant neural probes are subject to fluid forces during dissolution of
      polymer delivery vehicles.
AB  - Ultra-compliant neural probes implanted into tissue using a molded,
      biodissolvable sodium carboxymethyl cellulose (Na-CMC)-saccharide composite
      needle delivery vehicle are subjected to fluid-structure interactions that can
      displace the recording site of the probe with respect to its designed implant
      location. We applied particle velocimetry to analyze the behavior of ultra
      compliant structures under different implantation conditions for a range of CMC
      based materials and identified a fluid management protocol that resulted in the
      successful targeted depth placement of the recording sites. 

PMID- 24109997
TI  - Time-domain finite element models of electrochemistry in intracochlear
      electrodes.
AB  - Most neural prostheses feature metallic electrodes to act as an interface between
      the device and the physiological tissue. When charge is injected through these
      electrodes, potentially harmful reactions may result. Others have developed
      finite element models to evaluate the performance of stimulating electrodes in
      vivo. Few however, model an electrode-electrolyte interface, and many do not
      address electrode corrosion and safety concerns with respect to irreversible
      reactions. In this work, we successfully develop a time domain finite element
      model of cochlear implant electrodes that incorporate oxygen reduction and
      platinum oxidation reactions. We find that when electrodes are stimulated with
      current pulses (0.5 mA, 25 us), faradaic reactions may cause an increase in the
      peripheral enhancement of the current density. 

PMID- 24109998
TI  - A laboratory instrument for characterizing multiple microelectrodes.
AB  - The task of chronic monitoring and characterizing a large number of
      microelectrodes can be tedious and error prone, especially if needed to be done
      in vivo. This paper presents a lab instrument that automates the measurement and
      data processing, allowing for large numbers of electrodes to be characterized
      within a short time period. A version 1.0 of the Electrode Analyser System (EAS
      1.0) has already been used in various neural engineering laboratories, as well by
      one electrode array manufacturer. The goal of the current work is to implement
      the EAS 2.0 system that provides improved performance beyond that of the 1.0
      system, as well as reducing size and cost. 

PMID- 24110000
TI  - Investigation of the trade-off between time window length, classifier update rate
      and classification accuracy for restorative brain-computer interfaces.
AB  - Recently, the application of restorative brain-computer interfaces (BCIs) has
      received significant interest in many BCI labs. However, there are a number of
      challenges, that need to be tackled to achieve efficient performance of such
      systems. For instance, any restorative BCI needs an optimum trade-off between
      time window length, classification accuracy and classifier update rate. In this
      study, we have investigated possible solutions to these problems by using a
      dataset provided by the University of Graz, Austria. We have used a continuous
      wavelet transform and the Student t-test for feature extraction and a support
      vector machine (SVM) for classification. We find that improved results, for
      restorative BCIs for rehabilitation, may be achieved by using a 750 milliseconds
      time window with an average classification accuracy of 67% that updates every 32
      milliseconds. 

PMID- 24110001
TI  - Improving the performance of a neural-machine interface for prosthetic legs using
      adaptive pattern classifiers.
AB  - Pattern classification has been used for design of neural-machine interface (NMI)
      that identifies user intent. Our previous NMI based on electromyographic (EMG)
      signals and intrinsic mechanical feedback has shown great promise for neural
      control of artificial legs. In order to make this NMI practical, however, it is
      desired that classification algorithms can adapt to EMG pattern variations over
      time, caused by various physical and physiological changes. This study aimed to
      develop an adaptive pattern recognition framework in the NMI to improve the
      robustness of NMI performance over time. Two adaptive algorithms, i.e. entropy
      based adaptation and Learning From Testing Data (LIFT) adaptation, were presented
      and compared to the NMI with non-adaptive classifiers. Support vector machine
      (SVM) was selected as the basic classifier. Gradual change of EMG signals was
      simulated over time on EMG data collected from four transfemoral (TF) amputees.
      The preliminary results showed that the NMI with adaptive classifiers produced
      more consistent performance over time than the classifier without adaptation. The
      results of this preliminary study indicate the potential of using adaptive
      classifiers to improve the NMI reliability for neural control of powered
      prosthetic legs. 

PMID- 24110002
TI  - A brain-machine interface for control of burst suppression in medical coma.
AB  - Burst suppression is an electroencephalogram (EEG) marker of profound brain
      inactivation and unconsciousness and consists of bursts of electrical activity
      alternating with periods of isoelectricity called suppression. Burst suppression
      is the EEG pattern targeted in medical coma, a drug-induced brain state used to
      help recovery after brain injuries and to treat epilepsy that is refractory to
      conventional drug therapies. The state of coma is maintained manually by
      administering an intravenous infusion of an anesthetic, such as propofol, to
      target a pattern of burst suppression on the EEG. The coma often needs to be
      maintained for several hours or days, and hence an automated system would offer
      significant benefit for tight control. Here we present a brain-machine interface
      (BMI) for automatic control of burst suppression in medical coma that selects the
      real-time drug infusion rate based on EEG observations and can precisely control
      the burst suppression level in real time in rodents. We quantify the burst
      suppression level using the burst suppression probability (BSP), the brain's
      instantaneous probability of being in the suppressed state, and represent the
      effect of the anesthetic propofol on the BSP using a two-dimensional linear
      compartment model that we fit in experiments. We compute the BSP in real time
      from the EEG segmented into a binary time-series by deriving a two-dimensional
      state-space algorithm. We then derive a stochastic controller using both a linear
      quadratic-regulator strategy and a model predictive control strategy. The BMI can
      promptly change the level of burst suppression without overshoot or undershoot
      and maintains precise control of time-varying target levels of burst suppression
      in individual rodents in real time. 

PMID- 24110003
TI  - NeuroRex: a clinical neural interface roadmap for EEG-based brain machine
      interfaces to a lower body robotic exoskeleton.
AB  - In this communication, a translational clinical brain-machine interface (BMI)
      roadmap for an EEG-based BMI to a robotic exoskeleton (NeuroRex) is presented.
      This multi-faceted project addresses important engineering and clinical
      challenges: It addresses the validation of an intelligent, self-balancing,
      robotic lower-body and trunk exoskeleton (Rex) augmented with EEG-based BMI
      capabilities to interpret user intent to assist a mobility-impaired person to
      walk independently. The goal is to improve the quality of life and health status
      of wheelchair-bounded persons by enabling standing and sitting, walking and
      backing, turning, ascending and descending stairs/curbs, and navigating sloping
      surfaces in a variety of conditions without the need for additional support or
      crutches. 

PMID- 24110004
TI  - Online adaptive decoding of intended movements with a hybrid kinetic and
      kinematic brain machine interface.
AB  - Traditional brain machine interfaces for control of a prosthesis have typically
      focused on the kinematics of movement, rather than the dynamics. BMI decoders
      that extract the forces and/or torques to be applied by a prosthesis have the
      potential for giving the patient a much richer level of control across different
      dynamic scenarios or even scenarios in which the dynamics of the limb/environment
      are changing. However, it is a challenge to train a decoder that is able to
      capture this richness given the small amount of calibration data that is usually
      feasible to collect a priori. In this work, we propose that kinetic decoders
      should be continuously calibrated based on how they are used by the subject. Both
      intended hand position and joint torques are decoded simultaneously as a monkey
      performs a random target pursuit task. The deviation between intended and actual
      hand position is used as an estimate of error in the recently decoded joint
      torques. In turn, these errors are used to drive a gradient descent algorithm for
      improving the torque decoder parameters. We show that this approach is able to
      quickly restore the functionality of a torque decoder following substantial
      corruption with Gaussian noise. 

PMID- 24110005
TI  - An intent recognition strategy for transfemoral amputee ambulation across
      different locomotion modes.
AB  - Powered lower limb prostheses, capable of multiple locomotion modes, are being
      developed for transfemoral amputees. Current devices do not seamlessly transition
      between modes such as level walking, stairs and slopes. The purpose of this study
      was to develop an intent recognition system and test its performance across five
      different modes. A Dynamic Bayesian Network (DBN) was used for classification of
      neural and mechanical signals while four amputees completed a circuit containing
      level-walking, ramp ascent, ramp descent, stair ascent and stair descent. Our
      results indicate that transitional and steady-state stair steps had a high
      recognition rate (>99%), while ramp steps were significantly more difficult to
      classify (p<0.01) (13.7% error on transition steps and 1.3% on steady-state
      steps). With all five modes trained into the same system, the transitional error
      rate was 11.3%. Transitional error could be reduced by 31% by training the ramp
      ascent mode as level walking, and 92% by training both ramp ascent and descent as
      level walking. This is a viable solution when the level-walking mode can
      accommodate ramp modes which is currently the case with the ramp ascent. The high
      recognition rates for recognizing stairs shown in this study demonstrates the
      potential for an intent recognition system using neural information to allow
      amputees to naturally transition between locomotion modes on powered prostheses. 

PMID- 24110006
TI  - Effects of inertial properties of transfemoral prosthesis on leg swing motion
      during stair ascent.
AB  - Stair ascent, especially the step-over-step gait, is a difficult motor task for
      people with transfemoral amputation. Our previous study demonstrated the effects
      of foot placement on the leg swing of able-bodied subjects. The study examined
      stair ascent with full-foot contact (FFC) and half-foot contact (HFC) as
      ambulation strategies. The results suggested that HFC causes the leg swing to
      have a greater inertial motion than FFC, as well as the applicability of the
      stair ascent strategy for transfemoral amputees with transfemoral prostheses
      without a motorized prosthetic knee joint. The present study investigated the
      effects of the inertial properties of a transfemoral prosthesis on leg motion
      during the stair ascent swing phase in simulation trials. The joint moment at the
      hip became smaller than that of an able-bodied subject. The peak values of the
      horizontal and vertical components of the joint reaction force were approximately
      the same as those of an able-bodied subject. These results suggest that a
      transfemoral prosthesis leg swing can be achieved with similar or smaller kinetic
      demand at the hip joint when half-foot contact on the stair steps is used as a
      stair ascent strategy. The mass had the largest effect of the inertial properties
      on the variability of the simulated kinetic parameters. The results of the
      present study may enhance prosthesis design with regard to the inertial
      properties and usability. 

PMID- 24110007
TI  - Artificial proprioception for myoelectric control.
AB  - The typical control of myoelectric interfaces, be it in real-life prosthetic
      applications or laboratory settings, largely relies on visual feedback, while
      proprioceptive feedback from controlling muscles is not very informative about
      the task carried out. If proprioceptive feedback were artificially provided to a
      non-controlling limb, could it be effectively integrated into myoelectric
      control? In a two-dimensional myoelectric-controlled centre-out task, we aimed to
      restore proprioception by guiding subjects' right hands along the trajectory of a
      visual cursor they were controlling with isometric muscle contractions in their
      left hand. Overall task success was equally high with vision alone as it was with
      the additional proprioceptive signal, indicating that visual feedback was already
      sufficient. Still, presence of artificial proprioception did enhance control when
      visual feedback was not available. Interestingly, sensory integration of the
      proprioceptive information was established while it appeared to be redundant to
      existing visual feedback. However, utilization of the artificial proprioceptive
      signal was severely impaired when it was vertically mirrored with respect to
      visual feedback, outlining the importance of congruence of sensory modalities for
      implicit multi-sensory integration. 

PMID- 24110008
TI  - Pattern recognition control outperforms conventional myoelectric control in upper
      limb patients with targeted muscle reinnervation.
AB  - Pattern recognition myoelectric control shows great promise as an alternative to
      conventional amplitude based control to control multiple degree of freedom
      prosthetic limbs. Many studies have reported pattern recognition classification
      error performances of less than 10% during offline tests; however, it remains
      unclear how this translates to real-time control performance. In this
      contribution, we compare the real-time control performances between pattern
      recognition and direct myoelectric control (a popular form of conventional
      amplitude control) for participants who had received targeted muscle
      reinnervation. The real-time performance was evaluated during three tasks; 1) a
      box and blocks task, 2) a clothespin relocation task, and 3) a block stacking
      task. Our results found that pattern recognition significantly outperformed
      direct control for all three performance tasks. Furthermore, it was found that
      pattern recognition was configured much quicker. The classification error of the
      pattern recognition systems used by the patients was found to be 16% +/-(1.6%)
      suggesting that systems with this error rate may still provide excellent control.
      Finally, patients qualitatively preferred using pattern recognition control and
      reported the resulting control to be smoother and more consistent. 

PMID- 24110009
TI  - Motion recognition for simultaneous control of multifunctional transradial
      prostheses.
AB  - Electromyography (EMG) pattern-recognition based control strategies for
      multifunctional myoelectric prosthesis systems have been studied commonly in a
      controlled laboratory setting. Most previous efforts concentrated on evaluating
      the performance of EMG pattern-recognition algorithms in identifying one signal
      movement at a time. Therefore, the current motion classification methods would be
      limited with the difficulties in identifying the combined upper-limb motion
      classes that are commonly required in performing activities daily. In this paper,
      four improved classifier training schemes were proposed and investigated to
      address the difficulties mentioned above. Our preliminary results showed that
      three of the four proposed training schemes could improve the classification
      performance. The average classification accuracies of the three methods were
      75.10% +/- 9.71%, 76.95% +/- 8.02%, and 77.56% +/- 6.55% for the able-bodied
      subjects, and 63.38% +/- 7.51%, 62.55% +/- 9.06%, and 62.50% +/- 9.36% for the
      transradial amputees, respectively. These results suggested that the proposed
      methods could provide better classification performance in identifying the
      combined motions than the current methods. 

PMID- 24110010
TI  - Label-free monitoring of whole cell vitality.
AB  - The Intelligent Mobile Lab (IMOLA) delivers metabolic and morphological
      parameters of living cells in a label-free and real time way. It represents a key
      technology for the development of new cell-based assays. Electrochemical
      microsensors are used to measure the extracellular acidification (pH), cellular
      respiration (pO2), changes in cell number and morphology (electric impedance) in
      a controlled environment. These parameters are closely linked to the
      intracellular signaling network of the living cells. They are thus likely to
      respond sensitively to changes in cellular vitality. A wide spectrum of cell
      types can be tested with the system, including adherent and suspended cells,
      continuous cell lines, primary cells or tissue samples. The platform is described
      in detail and applications in the field's oncology, toxicology and environmental
      monitoring are shown. 

PMID- 24110011
TI  - Low-voltage DEP microsystem for submicron particle manipulation in artificial
      cerebrospinal fluid.
AB  - In this paper, we present a new low voltage biochip for micro and nanoparticle
      separation. The proposed system is designed to detect the concentration of
      particles after being separated through reconfigurable DEP-based electrode
      architecture. The described system in this work is focusing on the particle
      frequency dependent separation. Experimental results in artificial cerebrospinal
      fluid (ACSF) show that each particle has its own crossover frequency. Thus based
      on the crossover frequency, particles are attracted to the electrode's surface,
      while others are pushed away. Five different particles are tested with different
      diameters in the range of 500 nm to 4 um. All separation process is controlled by
      a CMOS chip fabricated using 0.18 um technology from TSMC and powered with 3.3 V.
      Efficient particle separation is observed with low voltage, below 3.3V unlike
      other techniques in the range of kV. The proposed platform includes an advanced
      PDMS based assembly technique for fast testing and prototyping in addition to
      reconfigurable electrode architecture. 

PMID- 24110012
TI  - Increased performance in genetic manipulation by modeling the dielectric
      properties of the rodent brain.
AB  - Genetic approaches to control DNA expression in different brain areas have
      provided an excellent system to characterize gene function in health and disease
      of animal models. With respect to others, in utero electroporation of exogenous
      DNA into progenitor cells committed to specific brain areas is the optimal
      solution in terms of simplicity and velocity. Indeed, this method entails one
      quick and easy surgical procedure aimed at DNA injection in the embryonic brain
      followed by brief exposure to a strong electric field by a bipolar electrode.
      Nevertheless, the technique is still lacking the necessary control and
      reliability in addressing the field. Moving from a theoretical model that
      accounts for the morphology and the dielectric properties of the embryonic brain,
      we developed here a set of novel and reliable experimental configurations based
      on the use of three electrodes for electroporation in mouse. Indeed, by means of
      a full 3D model of the embryonic brain and the surrounding environment, we showed
      that the distribution of the electric field can be finely tuned in order to
      target specific brain regions at a desired temporal window by proper placement of
      the three electrodes. In the light of this theoretical background, we
      manufactured a three-electrode device and performed model-guided experimental
      sessions. The result was an increased spatial control, extended time frames and
      unprecedented reliability of the genetic manipulation, with respect to the
      current state of the art. In particular, the outcomes of this method applied into
      the mouse model are reported here for the first time. 

PMID- 24110013
TI  - Optogenetic LED array for perturbing cardiac electrophysiology.
AB  - Optogenetics is the targeted genetic introduction of light-sensitive channels,
      such as Channelrhodopsin, and pumps, such as Halorhodopsin, into electrically
      excitable cells that enables high spatiotemporal electrical stimulation and
      inhibition by optical actuation. Technologies for inducing optogenetically-based
      electrical stimulation for investigating in vitro and in vivo neural
      perturbations have been described. However, modification of existing technologies
      or creation of new ones has not been described for chronic cardiac applications.
      Here, an LED array system for optogenetically perturbing cardiac
      electrophysiology is described. The overall layout of the system consists of an
      LED holder containing six LED's that deliver pulsed ~470 nm light to pluripotent
      stem cell-derived cardiomyocytes cultured in a 6-well tissue culture plate. The
      response of the cardiomyocytes is monitored by microscopy and the system is
      enclosed within a standard incubator. This system is relatively simple to create
      and uses mostly off-the-shelf components. The overall function of the system is
      to deliver chronic light stimulation over days to weeks to differentiating stem
      cell-derived cardiomyocytes in order to investigate perturbations in their
      electrophysiology. 

PMID- 24110014
TI  - Optical mapping of optically paced embryonic hearts.
AB  - Conduction maps of early embryonic hearts with optical mapping point to
      heterogeneous conduction patterns that quickly evolve over time. In adult hearts,
      electrical pacing is utilized to determine the anisotropy of the conduction
      patterns and the susceptibility of the tissue to arrhythmias. However, studying
      electrophysiology in developing hearts is limited due to their size. Electrical
      pacing creates an electrical artifact that obscures recordings from the entirety
      of early embryonic hearts. In this study, optical point stimulation using a 1440
      nm near-infrared diode laser with a 12-um diameter beam waist was used to pace
      embryonic quail hearts. Electrical activity was recorded across the surface of
      the embryonic hearts by high resolution optical mapping using di-4-ANEPPS and
      cytochalasin D. While there were no electrical artifacts produced by the optical
      point stimulation, an optical artifact due to thermal lensing did obscure the
      optical mapping near the point of stimulation. The optical artifact can be
      minimized by optimizing the stimulation parameters to minimize the energy
      deposited and can be further reduced by signal processing. Despite the presence
      of the optical artifact, the electrical activity over the majority of the heart
      can be obtained. 

PMID- 24110016
TI  - Sex determination from scapular length measurements by CT scans images in a
      Caucasian population.
AB  - Together with race, stature and age, sex is a main component of the biological
      identity. Thanks to its proportional correlation with parts of the human body,
      sex can be evaluated form the skeleton. The most accurate approach to determine
      sex by bone size is based on os coxae or skull. After natural disaster their
      presence can never be guaranteed, therefore the development of methods of sex
      determination using other skeletal elements can result crucial. Herein, sexual
      dimorphism in the human scapula is used to develop a two-variable discriminant
      function for sex estimation. We have enrolled 100 males and 100 females who
      underwent thoracic CT scan evaluation and we have estimated two scapular
      diameters. The estimation has been carried out by analyzing images of the
      scapulae of each patient after three dimensional post-processing reconstructions.
      The two-variable function allows to obtain an overall accuracy of 88% on the
      calibration sample. Furthermore, we have employed the mentioned function on a
      collection of 10 individual test sample from the collection of the "Museo di
      Anatomia Umana di Firenze" of the Universita degli Studi di Firenze; sex has been
      correctly predicted on 9 skeletons.

PMID- 24110015
TI  - Electrical stimulation via a biocompatible conductive polymer directs retinal
      progenitor cell differentiation.
AB  - The goal of this study was to simulate in vitro the spontaneous electrical wave
      activity associated with retinal development and investigate if such
      biometrically designed signals can enhance differentiation of mouse retinal
      progenitor cells (mRPC). To this end, we cultured cells on an electroconductive
      transplantable polymer, polypyrrole (PPy) and measured gene expression and
      morphology of the cells. Custom-made 8-well cell culture chambers were designed
      to accommodate PPy deposited onto indium tin oxide-coated (ITO) glass slides,
      with precise control of the PPy film thickness. mRPCs were isolated from post
      natal day 1 (P1) green fluorescent protein positive (GFP+) mice, expanded, seeded
      onto PPY films, allowed to adhere for 24 hours, and then subjected to electrical
      stimulation (100 uA pulse trains, 5 s in duration, once per minute) for 4 days.
      Cultured cells and non-stimulated controls were processed for immunostaining and
      confocal analysis, and for RNA extraction and quantitative PCR. Stimulated cells
      expressed significantly higher levels of the early photoreceptor marker cone-rod
      homebox (CRX, the earliest known marker of photoreceptor identity), and protein
      kinase-C (PKC), and significantly lower levels of the glial fibrillary acidic
      protein (GFAP). Consistently, stimulated cells developed pronounced neuronal
      morphologies with significantly longer dendritic processes and larger cell bodies
      than non-stimulated controls. Taken together, the experimental evidence shows
      that the application of an electrical stimulation designed based on retinal
      development can be implemented to direct and enhance retinal differentiation of
      mRPCs, suggesting a role for biomimetic electrical stimulation in directing
      progenitor cells toward neural fates. 

PMID- 24110017
TI  - Correcting LCD luminance non-uniformity for threshold Saccadic Vector Optokinetic
      Perimetry (SVOP).
AB  - The accurate assessment of visual field function can provide valuable information
      on a range of visual disorders. Saccadic Vector Optokinetic Perimetry (SVOP) is a
      novel instrument for measuring supra-threshold visual fields in young children
      who are otherwise unable to perform Automated Static Perimetry (ASP). However,
      limitations in Liquid Crystal Display (LCD) technology restrict the ability of
      SVOP to determine threshold values at various points in the visual field, often
      required in detailed perimetry examinations. This paper introduces a purpose
      specific LCD luminance non-uniformity compensation approach to address this
      limitation. Thorough quantitative evaluation identifies the effectiveness of the
      proposed approach in (i) compensating for luminance non-uniformities across an
      LCD, and (ii) enabling SVOP to perform accurate and precise threshold visual
      field tests. The findings demonstrate that SVOP provides a promising alternative
      to the current threshold ASP standard (Humphrey Field Analyser). 

PMID- 24110018
TI  - Comparison between transmission and scattering spectrum reconstruction methods
      based on EPID images.
AB  - Numerous improved physics-based methods for Linac photon spectra reconstruction
      have been published; some of them are based on transmission data analysis and
      others on scattering data. In this work, the two spectrum unfolding approaches
      are compared in order to experimentally validate its robustness and to determine
      which is the optimal methodology for application on a clinical quality assurance
      routine. Both studied methods are based on EPID images generated when the
      incident photon beam impinges onto plastic blocks. The distribution of
      transmitted/scatter radiation produced by this object centered at the beam field
      size was measured. Measurements were performed using a 6 MeV photon beam produced
      by the linear accelerator. The same radiation distribution conditions were also
      simulated with Monte Carlo code for a series of monoenergetic identical geometry
      photon beams for both cases. Two systems of linear equations were generated to
      combine the polyenergetic EPID measurements with the monoenergetic simulation
      results. Regularization techniques were applied to solve the systems for
      obtaining the incident photon spectrum. We present a comparison between the well
      known photon Spectral Reconstruction based on Transmission Data (Trans-based)
      technology and the Spectral Reconstruction based on Scattering Data (Scatt
      based), which we both developed using EPID images. It is shown that Trans-based
      reconstruction results display much better agreement with photon spectrum
      theoretical predictions. 

PMID- 24110020
TI  - Artificial Neural Networks as an alternative to traditional fall detection
      methods.
AB  - Falls are common events among older adults and may have serious consequences.
      Automatic fall detection systems are becoming a popular tool to rapidly detect
      such events, helping family or health personal to rapidly help the person that
      falls. This paper presents the results obtained in the process of testing a new
      fall detection method, based on Artificial Neural Networks (ANN). This method
      intends to improve fall detection accuracy, by avoiding the traditional threshold
      - based fall detection methods, and introducing ANN as a suitable option on this
      application.Also ANN have low computational cost, this characteristic makes them
      easy to implement on a portable device, comfortable to be wear by the patient. 

PMID- 24110019
TI  - Epilepsy analytic system with cloud computing.
AB  - Biomedical data analytic system has played an important role in doing the
      clinical diagnosis for several decades. Today, it is an emerging research area of
      analyzing these big data to make decision support for physicians. This paper
      presents a parallelized web-based tool with cloud computing service architecture
      to analyze the epilepsy. There are many modern analytic functions which are
      wavelet transform, genetic algorithm (GA), and support vector machine (SVM)
      cascaded in the system. To demonstrate the effectiveness of the system, it has
      been verified by two kinds of electroencephalography (EEG) data, which are short
      term EEG and long term EEG. The results reveal that our approach achieves the
      total classification accuracy higher than 90%. In addition, the entire training
      time accelerate about 4.66 times and prediction time is also meet requirements in
      real time. 

PMID- 24110021
TI  - Automated detection of sleep apnea in infants using minimally invasive sensors.
AB  - To address the difficult and necessity of early detection of sleep apnea hypopnea
      syndrome in infants, we present a study into the effectiveness of pulse oximetry
      as a minimally invasive means of automated diagnosis of sleep apnea in infants.
      Overnight polysomnogram data from 328 infants were used to extract time-domain
      based oximetry features and scored arousal data for each subject. These records
      were then used to determine apnea events and to train a classifier model based on
      linear discriminants. Performance of the classifier was evaluated using a leave
      one-out cross-validation scheme and an accuracy of 68% was achieved, with a
      specificity of 68.6% and a sensitivity of 55.9%. 

PMID- 24110022
TI  - IEEE802.15.6 -based multi-accelerometer WBAN system for monitoring Parkinson's
      disease.
AB  - In this paper we present a detailed example of a wireless body area network
      (WBAN) scenario utilizing the recent IEEE802.15.6 standard as applied to a multi
      accelerometer system for monitoring Parkinson's disease and fall detection. Ultra
      wideband physical layer and standard security protocols are applied to meet
      application requirements for data rate and security. 

PMID- 24110023
TI  - IEEE802.15.6 NB portable BAN clinic and M2M international standardization.
AB  - The increase of non communicable diseases (NCDs) will change the direction of
      health services to emphasize the role of preventive medicine in healthcare
      services. The first short-range medical body are network (BAN) standard
      IEEE802.15.6 is expected to be used for secure and user-friendly sensor devices
      for portable medical equipment. A BAN is an enabler for uploading medical data to
      a backend system for remote diagnoses and treatment. Machine-to-Machine (M2M)
      infrastructure is also a key technology for providing flexible and affordable
      services extending electronic health record (EHR) systems. This paper proposes a
      BAN-based portable clinic that collects health-check data from user-friendly
      medical devices and sensors and sends the data to a local backend server, and it
      evaluates the clinic in fields of actual usage. We discuss issues experienced
      from actual deployment of the system and focus on integrating it into upcoming
      healthcare M2M infrastructure to achieve affordable and dependable clinic
      services. We explain the components and workflow of the clinic and the system
      model. The system is set up at a temporary health center and has a network link
      to a remote medical help center. The paper concludes with our plan to introduce
      our system to contribute to internationally standardized preventive medicine. 

PMID- 24110024
TI  - Self-powered wireless disposable sensor for welfare application.
AB  - A self-powered urinary incontinence sensor consisting of a flexible urine
      activated battery and a wireless transmitter has been developed as an application
      for wireless biosensor networks. The flexible urine-activated battery is embedded
      in a disposal diaper and makes possible both the sensing of urine leakage and
      self-powered operation. An intermittent power-supply circuit that uses an
      electric double-layer capacitor (EDLC) with a small internal resistance
      suppresses the supply voltage drop due to the large internal resistance of the
      battery. This circuit supplies the power to a wireless transmitter. A 315-MHz
      band wireless transmitter performs low-power operation. To verify the
      effectiveness of the circuit scheme, we fabricated a prototype sensor system.
      When 80 cc of urine is poured onto the diaper, the battery outputs a voltage of 1
      V; and the sensor can transmit an ID signal over a distance of 5 m. 

PMID- 24110025
TI  - GramHealth: a bottom-up approach to provide preventive healthcare services for
      unreached community.
AB  - Insufficient healthcare facilities and unavailability of medical experts in rural
      areas are the two major reasons that kept the people unreached to healthcare
      services. Recent penetration of mobile phone and the demand to basic healthcare
      services, remote health consultancy over mobile phone became popular in
      developing countries. In this paper, we introduce two such representative
      initiatives from Bangladesh and discuss the technical challenges they face to
      serve a remote patient. To solve these issues, we have prototyped a box with
      necessary diagnostic tools, we call it a "portable clinic" and a software tool,
      "GramHealth" for managing the patient information. We carried out experiments in
      three villages in Bangladesh to observe the usability of the portable clinic and
      verify the functionality of "GramHealth". We display the qualitative analysis of
      the results obtained from the experiment. GramHealth DB has a unique combination
      of structured, semi-structured and un-structured data. We are currently looking
      at these data to see whether these can be treated as BigData and if yes, how to
      analyze the data and what to expect from these data to make a better clinical
      decision support. 

PMID- 24110026
TI  - Evaluation of "Portable Health Clinic" with BAN standard for 10K subjects in
      Bangladesh.
AB  - Management system of chronic diseases in developing countries and post-disaster
      situation has been required. Body area network (BAN, IEEE 802.15.6) is expected
      to be useful in medical field. To evaluate BAN standard, we are implementing BAN
      in our attache case type sensor set named "Portable Health Clinic" (PHC), and
      conducting systematic health checkup in rural and urban areas in Bangladesh.
      (Methods) In the PHC, we packed weight scale, blood pressure meter, blood sugar
      meter, body thermometer, pulse oxymeter, as electrical devices, and tape measure
      (for height, waist and hip), urine test tape (for urine sugar, urine protein and
      urobilinogen) as no-electrical devices. We provided checkup in rural villages and
      urban companies in Bangladesh by PHC, and transmitted data by cellphone network
      to the data center in Dhaka. Individual health condition was categorized into 4
      grades, green (healthy), yellow (caution), orange (affected), and red (emergent)
      by international diagnosis standards of diseases. We provided telemedicine for
      orange and red, and tele-prescription for hypertensive patients. We are making
      all sensor devices implemented with BAN. (Results) The health checkup was
      provided to 5498 subjects until the end of 2012 and categorized green 14%, yellow
      66%, orange 17%, and red 3%. The result shows its potency as an effective
      healthcare system in developing countries and in a chronic phase after disaster.
      We continue to provide the e-health service for 10K-15 K people each year until
      March 2014. 

PMID- 24110027
TI  - On IEEE 802.15.6 IR-UWB receivers - simulations for DBPSK modulation.
AB  - In 2002, Federal Communications Commission (FCC) was the first in defining
      regulations for ultra wideband (UWB) communications followed by Europe and Japan
      some years later. Focusing on impulse radio (IR) UWB, in 2007 was the time for
      the first published standard targeting in personal area networks, released by the
      IEEE. The second IEEE released standard including UWB definitions is targeted for
      wireless body area networks (WBAN) and was published in 2012. As the wireless
      communications has been and will be passing through almost any levels in society,
      the natural step with WBAN is using it in different medical, healthcare and
      wellbeing applications. The arguments for these are related to the modern
      lifestyle, in which people have increasingly more free time and are more
      interested in taking care of their health and wellbeing. Another challenge is the
      population composition, i.e., aging in developed countries which call for new
      solutions and procedures, particularly from cost wise. In this paper, we are
      evaluating UWB receivers based on the IEEE 802.15.6 physical layer definitions
      and capable of detecting differentially encoded modulation. The evaluation is
      performed using two different WBAN channel models. 

PMID- 24110028
TI  - Comparison of averaging and regression techniques for estimating Event Related
      Potentials.
AB  - The traditional method of estimating an Event Related Potential (ERP) is to take
      the average of signal epochs time locked to a set of similar experimental events.
      This averaging method is useful as long as the experimental procedure can
      sufficiently isolate the brain or non-brain process of interest. However, if
      responses from multiple cognitive processes, time locked to multiple classes of
      closely spaced events, overlap in time with varying inter-event intervals,
      averaging will most likely fail to identify the individual response time courses.
      For this situation, we study estimation of responses to all recorded events in an
      experiment by a single model using standard linear regression (the rERP
      technique). Applied to data collected during a Rapid Serial Visual Presentation
      (RSVP) task, our analysis shows: (1) The rERP technique accounts for more
      variance in the data than averaging when individual event responses are highly
      overlapping; (2) the variance accounted for by the estimates is concentrated into
      a fewer ICA components than raw EEG channel signals. 

PMID- 24110029
TI  - Dynamic modeling of respiratory sinus arrhythmia component from HRV with
      multivariate Kalman smoother.
AB  - The estimates of heart rate variability (HRV) low frequency (LF) and high
      frequency (HF) components with constant frequency bands may distort when the
      frequency of respiratory sinus arrhythmia induced HF component approaches the LF
      HF frequency limit. In this study we present a method for dynamically estimating
      the LF-HF limit and dividing the spectrum to LF and HF components that can
      overlap. The method is based on multivariate autoregressive model which is solved
      dynamically with Kalman smoother algorithm. The spectra of each individual pole
      with all the zeros are calculated and then multiplied with a Hanning window on
      the pole frequency. These spectra are summed to LF or HF components. The method
      was applied to three subjects whose electrocardiogram and respiration was
      recorded during a controlled breathing protocol. The results show that the HF
      component power increases when breathing frequency decreases. Also the component
      powers obtained with the presented method are reliable even when LF and HF
      frequencies are close to each other. 

PMID- 24110030
TI  - Distinction between added-energy and phase-resetting mechanisms in non-invasively
      detected somatosensory evoked responses.
AB  - Non-invasively recorded averaged event-related potentials (ERP) represent a
      convenient opportunity to investigate human brain perceptive and cognitive
      processes. Nevertheless, generative ERP mechanisms are still debated. Two
      previous approaches have been contested in the past: the added-energy model in
      which the response raises independently from the ongoing background activity, and
      the phase-reset model, based on stimulus-driven synchronization of oscillatory
      ongoing activity. Many criteria for the distinction of these two models have been
      proposed, but there is no definitive methodology to disentangle them, owing also
      to the limited information at the single trial level. Here, we propose a new
      approach combining low-noise EEG technology and multivariate decomposition
      techniques. We present theoretical analyses based on simulated data and identify
      in high-frequency somatosensory evoked responses an optimal target for the
      distinction between the two mechanisms. 

PMID- 24110031
TI  - Discriminating between best performing features for seizure detection and data
      selection.
AB  - Seizure detection algorithms have been developed to solve specific problems, such
      as seizure onset detection, occurrence detection, termination detection and data
      selection. It is thus inherent that each type of seizure detection algorithm
      would detect a different EEG characteristic (feature). However most feature
      comparison studies do not specify the seizure detection problem for which their
      respective features have been evaluated. This paper shows that the best
      features/algorithm bases are not the same for all types of algorithms but depend
      on the type of seizure detection algorithm wanted. To demonstrate this, 65
      features previously evaluated for online seizure data selection are re-evaluated
      here for seizure occurrence detection, using performance metrics pertinent to
      each seizure detection type whilst keeping the testing methodology the same. The
      results show that the best performing features/algorithm bases for data selection
      and occurrence detection algorithms are different and that it is more challenging
      to achieve high detection accuracy for the former seizure detection type. This
      paper also provides a comprehensive evaluation of the performance of 65 features
      for seizure occurrence detection to aid future researchers in choosing the best
      performing feature(s) to improve seizure detection accuracy. 

PMID- 24110032
TI  - Cardiac arrhythmia detection using combination of heart rate variability analyses
      and PUCK analysis.
AB  - This paper presents cardiac arrhythmia detection using the combination of a heart
      rate variability (HRV) analysis and a "potential of unbalanced complex kinetics"
      (PUCK) analysis. Detection performance was improved by adding features extracted
      from the PUCK analysis. Initially, R-R interval data were extracted from the
      original electrocardiogram (ECG) recordings and were cut into small segments and
      marked as either normal or arrhythmia. HRV analyses then were conducted using the
      segmented R-R interval data, including a time-domain analysis, frequency-domain
      analysis, and nonlinear analysis. In addition to the HRV analysis, PUCK analysis,
      which has been implemented successfully in a foreign exchange market series to
      characterize change, was employed. A decision-tree algorithm was applied to all
      of the obtained features for classification. The proposed method was tested using
      the MIT-BIH arrhythmia database and had an overall classification accuracy of
      91.73%. After combining features obtained from the PUCK analysis, the overall
      accuracy increased to 92.91%. Therefore, we suggest that the use of a PUCK
      analysis in conjunction with HRV analysis might improve performance accuracy for
      the detection of cardiac arrhythmia. 

PMID- 24110033
TI  - Polycarbazole-based organic photodiodes for highly sensitive chemiluminescent
      immunoassays.
AB  - It is reported the development of a polycarbazole-based organic photodetector for
      chemiluminescent immunoassays. The optical detector comprised a 1?4 blend by
      weight of poly [N-9'-heptadecanyl-2,7-carbazole-alt-5,5-(4',7'-di-2-thienyl
      2',1',3'-benzothiadiazole)] (PCDTBT) and [6,6]-phenyl C71-butyric acid methyl
      ester (PC70BM). Optimization of the photodetector design was conducted aiming to
      maximize photosensitivity and reduce the background level. Quantitation of
      recombinant human thyroid stimulating hormone indicated good linearity and
      yielded a detection sensitivity of ~3.7 nA * nM(-1) and a detection limit of 80
      pg/ml. 

PMID- 24110034
TI  - Effects of LED-backlit computer screen and emotional selfregulation on human
      melatonin production.
AB  - Melatonin is a circadian hormone transmitted via suprachiasmatic nucleus (SCN) in
      the hypothalamus and sympathetic nervous system to the pineal gland. It is a
      hormone necessary to many human functions such as immune, cardiovascular, neuron
      and sleep/awake functions. Since melatonin enhancement or suppression is reported
      to be closely related to the photic information from retina, in this paper, we
      aim further to study both the lighting condition and the emotional self
      regulation in different lighting conditions together with their effects on the
      production of human melatonin. In this experiment, five participants are in three
      light exposure conditions by LED backlit computer screen (No light, Red light
      (~650nm) and Blue light (~470nm)) for 30 minute (8-8:30pm), then they are
      collected saliva both before and after the experiments. After the experiment, the
      participants are also asked to answer the emotional self-regulation questionnaire
      of PANAS and BRUMS regarding each light exposure condition. These results show
      that positive mood mean difference of PANAS between no light and red light is
      significant with p=0.001. Tension, depression, fatigue, confusion and vigor from
      BRUMS are not significantly changed while we can observe the significant change
      in anger mood. Finally, we can also report that the blue light of LED-backlit
      computer screen significantly suppress melatonin production (91%) more than red
      light (78%) and no light (44%). 

PMID- 24110035
TI  - A household LOC device for online monitoring bacterial pathogens in drinking
      water with green design concept.
AB  - Bacterial waterborne pathogens often threaten the water safety of the drinking
      water system. In order to protect the health of home users, a household lab-on-a
      chip (LOC) device was developed for online monitoring bacterial pathogens in
      drinking water, which are in accord with green design concept. The chip
      integrated counter-flow micromixers, a T-junction droplet generator and time
      delay channels (TD-Cs), which can mix water sample and reactants into droplets in
      air flow and incubate the droplets in the LOC for about 18 hours before
      observation. The detection module was simplified into a transparent observation
      chamber, from which the home users can evaluate the qualitative result by naked
      eyes. The liquid waste generated by the LOC system was sterilized and absorbed by
      quicklime powders. No secondary pollution was found. The preliminary test of the
      prototype system met its design requirements. 

PMID- 24110037
TI  - Fabrication of polydimethylsiloxane (PDMS) - based multielectrode array for
      neural interface.
AB  - Flexible multielectrode arrays (MEAs) are being developed with various materials,
      and polyimide has been widely used due to the conveniece of process. Polyimide is
      developed in the form of photoresist. And this enable precise and reproducible
      fabrication. PDMS is another good candidate for MEA base material, but it has
      poor surface energy and etching property. In this paper, we proposed a better
      fabrication process that could modify PDMS surface for a long time and open the
      site of electrode and pad efficiently without PDMS etching. 

PMID- 24110036
TI  - Concept for E.coli detection using interdigitated microelectrode impedance
      sensor.
AB  - This paper presents the concept to detect Escherichia coli O157:H7 based on
      electrochemical impedance spectroscopy at interdigitated microelectrode.
      Interdigitated microelectrode structures was designed and fabricated, with glass
      as substrate material and gold electrodes. The performance of the sensors was
      studied by measuring the capacitance in air and impedance spectra in DI water.
      The feasibility of the fabricated sensor for detecting different concentrations
      of Escherichia coli in water was demonstrated. Electrochemical impedance
      spectroscopy (EIS) was employed as the detection technique. The impedance based
      response significant change for different E.coli concentrations in the frequency
      range between 1 kHz to 100 kHz. 

PMID- 24110038
TI  - Electromagnetic levitation platform for wireless study of insect flight
      neurophysiology.
AB  - An electromagnetic levitation platform for use in a light emitting diode (LED)
      arena based virtual reality environment was developed for wireless recording of
      neural and neuromuscular signals from the flight related muscle groups in Manduca
      sexta. The platform incorporates the use of Early Metamorphosis Insertion
      Technology to implant recording electrodes into the flight muscles of late stage
      pupal moths. Analysis of the insects' response to changes in the LED arena
      rotation direction indicate that this setup could be used to perform a variety of
      flight behavior studies during yaw maneuvers. 

PMID- 24110039
TI  - Comparison between red, green and blue light reflection photoplethysmography for
      heart rate monitoring during motion.
AB  - Reflection photoplethysmography (PPG) using 530 nm (green) wavelength light has
      the potential to be a superior method for monitoring heart rate (HR) during
      normal daily life due to its relative freedom from artifacts. However, little is
      known about the accuracy of pulse rate (PR) measured by 530 nm light PPG during
      motion. Therefore, we compared the HR measured by electrocadiography (ECG) as a
      reference with PR measured by 530, 645 (red), and 470 nm (blue) wavelength light
      PPG during baseline and while performing hand waving in 12 participants. In
      addition, we examined the change of signal-to-noise ratio (SNR) by motion for
      each of the three wavelengths used for the PPG. The results showed that the limit
      of agreement in Bland-Altman plots between the HR measured by ECG and PR measured
      by 530 nm light PPG (+/-0.61 bpm) was smaller than that achieved when using 645
      and 470 nm light PPG (+/-3.20 bpm and +/-2.23 bpm, respectively). The DeltaSNR
      (the difference between baseline and task values) of 530 and 470nm light PPG was
      significantly smaller than DeltaSNR for red light PPG. In conclusion, 530 nm
      light PPG could be a more suitable method than 645 and 470nm light PPG for
      monitoring HR in normal daily life. 

PMID- 24110040
TI  - Evaluation of a combined reflectance photoplethysmography and laser Doppler
      flowmetry surface probe.
AB  - This study presents evaluation of a system combining laser Doppler flowmetry and
      photoplethysmography (PPG) in a single probe for the simultaneous measurement of
      perfusion and blood flow in the finger. A cuff sphygmomanometer was used to
      partially occlude the arteries supplying the hand to investigate the effect of
      low pressure on photoplethysmographic and laser Doppler signals and also on
      calculated arterial blood oxygen saturation values (SpO2). Red and infrared PPG
      and Doppler signals were recorded from six healthy volunteers at various
      pressures. Good quality signals were recorded in all subjects at low cuff
      pressures; however both PPG and Doppler signals showed a gradual decrease in
      amplitude at higher pressures. SpO2 values calculated from the PPG signals showed
      higher deviation from measurements made on the contralateral hand using a
      commercial pulse oximeter at higher cuff pressures. 

PMID- 24110041
TI  - Esophageal SpO2 measurements from a pediatric burns-patient: a case study.
AB  - Pulse oximetry is being used in everyday clinical practice in anesthesia
      utilizing peripheral saturation sensors. However, it may be unreliable in certain
      clinical situations such as peripheral hypoperfusion. Similar situations occur in
      burns patients and more importantly burns to extremities which limit the sites
      available for measurement of peripheral oxygen saturation (SpO2). To overcome
      these limitations, the esophagus has been investigated as an alternative
      measurement site, as perfusion may be preferentially preserved centrally. A
      miniaturized reflectance esophageal saturation (SpO2 probe has been constructed
      utilizing infrared and red photodiodes and a photodetector. Our case study was
      aimed at evaluating the reliability of esophageal pulse oximetry in a major burns
      infant. Measurable photoplethysmographic (PPG) traces and SpO2 values were
      obtained in the neonatal esophagus. It was found that the esophageal pulse
      oximeter results were in good agreement with oxygen saturation measurements
      obtained by a commercial ear lobe pulse oximeter. This study suggests that the
      esophagus can be used as an alternative site for monitoring arterial blood oxygen
      saturation by pulse oximetry in burned infants. 

PMID- 24110042
TI  - Devepopment of an optical probe to investigate the suitability of measuring
      photoplethysmographs and blood oxygen saturation from the human auditory canal.
AB  - Pulse oximetry has become a standard for patient monitoring in the operating
      room, and the finger is the most common site used for monitoring blood oxygen
      saturation (SpO2). However, SpO2 measurements made from extremities such as the
      finger, ear lobe and toes become susceptible to inaccuracies, when patients
      become hypothermic, hypovolemic and vasoconstrictive. This is due to the week
      arterial pulsations detected in these conditions. To overcome this limitation,
      the external auditory canal has been proposed as an alternative monitoring site
      for estimating SpO2, on the hypothesis that this central site will be better
      perfused. A dual wavelength optoelectronic sensor along with a processing system
      was developed to investigate the suitability of measuring photoplethysmographic
      (PPG) signals and SpO2 values in the human auditory canal. A pilot study was
      conducted on 12 healthy volunteers to validate the developed sensor. The red and
      infrared PPG signals obtained from all the volunteers were of very good quality.
      The SpO2 values recorded from the ear canal were compared with simultaneously
      acquired data from a commercial finger pulse oximeter. The results show good
      correlation between the commercial pulse oximeter and the custom made ear canal
      sensor (r(2) = 0.825). 

PMID- 24110043
TI  - Low cost MATLAB-based pulse oximeter for deployment in research and development
      applications.
AB  - Problems such as motion artifact and effects of ambient lights have forced
      developers to design different signal processing techniques and algorithms to
      increase the reliability and accuracy of the conventional pulse oximeter device.
      To evaluate the robustness of these techniques, they are applied either to
      recorded data or are implemented on chip to be applied to real-time data.
      Recorded data is the most common method of evaluating however it is not as
      reliable as real-time measurements. On the other hand, hardware implementation
      can be both expensive and time consuming. This paper presents a low cost MATLAB
      based pulse oximeter that can be used for rapid evaluation of newly developed
      signal processing techniques and algorithms. Flexibility to apply different
      signal processing techniques, providing both processed and unprocessed data along
      with low implementation cost are the important features of this design which
      makes it ideal for research and development purposes, as well as commercial,
      hospital and healthcare application. 

PMID- 24110044
TI  - Using an ambulatory stress monitoring device to identify relaxation due to
      untrained deep breathing.
AB  - The objective of this paper is to assess the efficacy of deep breathing as a
      relaxation activity using a wearable stress monitor. For this purpose, we
      developed a protocol with different mentally stressful activities interleaved
      with regular sessions of deep breathing. We used three physiological sensors: a
      heart rate monitor, a respiration sensor, and an electrodermal activity sensor,
      to extract parameters that are consistent with the dominance of the sympathetic
      nervous system. Our results indicate that a large number of subjects were not
      able to perform the paced deep breathing exercise properly, which caused their
      stress levels to increase rather than to decrease. The study also showed that our
      wearable stress monitor can be used to monitor breathing technique and assess its
      effectiveness in relaxing individuals. 

PMID- 24110045
TI  - Integration of user centered design in the development of health monitoring
      system for elderly.
AB  - This paper presents a health monitoring system by incorporating the approach of
      user centered design (UCD) for enhancing system usability for the elderly. The
      system is designed for monitoring cardiovascular diseases (CVD) related
      physiological signals including electrocardiogram (ECG), pulse wave (PW) and body
      weight (BW). Ease of use and non-obtrusiveness are two key requirements for
      design criteria. Our health monitoring system is designed on three levels:
      personal medical device layer, mobile application layer and remote central
      service layer. A chair-based apparatus was built for physiological signal
      acquisition and a mobile application was developed for data delivery and health
      management. Finally, usability evaluation was conducted and the system efficiency
      was quantitatively analyzed by system usability scale (SUS). The results
      demonstrate that the performance of the system is acceptable for the elderly and
      the UCD principle is helpful for health system design. 

PMID- 24110046
TI  - Optimal frequency range for medical radar measurements of human heartbeats using
      body-contact radar.
AB  - In this paper the optimal frequency range for heartbeat measurements using body
      contact radar is experimentally evaluated. A Body-contact radar senses
      electromagnetic waves that have penetrated the human body, but the range of
      frequencies that can be used are limited by the electric properties of the human
      tissue. The optimal frequency range is an important property needed for the
      design of body-contact radar systems for heartbeat measurements. In this study
      heartbeats are measured using three different antennas at discrete frequencies
      from 0.1 - 10 GHz, and the strength of the received heartbeat signal is
      calculated. To characterize the antennas, when in contact with the body, two port
      S-parameters(?) are measured for the antennas using a pork rib as a phantom for
      the human body. The results shows that frequencies up to 2.5 GHz can be used for
      heartbeat measurements with body-contact radar. 

PMID- 24110047
TI  - Noncontact measurement of cardiac beat by using active stereo with waved-grid
      pattern projection.
AB  - We propose a method to observe cardiac beat from 3D shape information of body
      surface by using the active stereo with waved-grid pattern projection, and report
      preliminary experiments to evaluate validities of the proposed method. By
      comparing results of our method with those of electrocardiogram (ECG), we
      confirmed sufficient correspondences between peak intervals of depth changes
      between contiguous frames measured by the active stereo and R-R intervals
      measured by ECG. We proposed the visualization of the spatial distribution of
      depth change plotted on the 3D shape of chest surface. We confirm that the
      spatial phase difference, which is caused by heart pump ability, appears in the 3
      D shape change of chest surface. 

PMID- 24110048
TI  - Packet radar spectrum recovery for physiological signals.
AB  - Packet Doppler radar is investigated for extracting physiological signals. System
      on Chip is employed as a signal source in packet mode, and it transmits signals
      intermittently at 2.405 GHz to save power. Reflected signals are demodulated
      directly by spectral analysis of received pulses in the baseband. Spectral
      subtraction, using data from an empty room, is applied to extract the periodic
      movement. It was experimentally demonstrated that frequency of the periodic
      motion can be accurately extracted using this technique. Proposed approach
      reduces the computation complexity of the signal processing part effectively. 

PMID- 24110049
TI  - Neural network based algorithm for automatic identification of cough sounds.
AB  - Cough is the most common symptom of the several respiratory diseases containing
      diagnostic information. It is the best suitable candidate to develop a simplified
      screening technique for the management of respiratory diseases in timely manner,
      both in developing and developed countries, particularly in remote areas where
      medical facilities are limited. However, major issue hindering the development is
      the non-availability of reliable technique to automatically identify cough
      events. Medical practitioners still rely on manual counting, which is laborious
      and time consuming. In this paper we propose a novel method, based on the neural
      network to automatically identify cough segments, discarding other sounds such a
      speech, ambient noise etc. We achieved the accuracy of 98% in classifying 13395
      segments into two classes, 'cough' and 'other sounds', with the sensitivity of
      93.44% and specificity of 94.52%. Our preliminary results indicate that method
      can develop into a real-time cough identification technique in continuous cough
      monitoring systems. 

PMID- 24110050
TI  - Local effect of compression stockings on skin microcirculatory activity through
      the measurement of skin effective thermal conductivity.
AB  - This paper presents a preliminary study to demonstrate the instantaneous local
      effect of compression stocking (Class 2) on skin microcirculatory activity. The
      measurement needs to be carefully performed as the sensor is placed under the
      garment. To assess the local effect of compression stockings, we use the
      ambulatory device Hematron located on the calf under the garment. Skin
      microcirculatory activity is assessed through the skin's effective thermal
      conductivity measurement. A specific housing for the sensor has been designed to
      avoid excessive pressure induced by the sensor when squeezed by stockings. The
      experiment, conducted on ten healthy subjects, comprised two stages: without and
      with compression stockings. Skin effective thermal conductivity was recorded at
      three successive positions (supine, sitting and standing). Significant
      improvement in skin microcirculatory activity was recorded by the Hematron device
      for the three positions. We have also demonstrated that Hematron sensor can be
      used under compression stockings. 

PMID- 24110051
TI  - A novel approach for deriving global activation maps from non-averaged cardiac
      optical signals.
AB  - Cardiac arrhythmias are often characterized by non-repetitive complex activation
      sequences. The properties of electrical activity in cardiac tissue, such as
      activation time (AT), can be accurately determined using optical imaging of
      electrical signals using voltage-sensitive dyes. The electrical AT of optical
      action potentials is known to accurately correlate with the time of the maximal
      derivative (dF/dt(max)) of the upstroke of ensemble averaged optical signals. The
      sensitivity of dF/dt(max) to noise is therefore problematic for mapping AT from
      nonrepetitive activity. Here we experimentally evaluated a novel method to
      determine activation times (AT) from non-averaged epicardial optical signals. The
      method depends upon the time delays of activation between adjacent pixels
      developing a global AT map, as opposed to measuring local AT from each pixel
      independently based on dF/dt(max). ATs from dF/dt(max) and global AT maps of non
      ensemble averaged signals were correlated with averaged signals. Global ATs
      improved linear correlation coefficients and accuracy of AT patterns.
      Furthermore, global AT maps were significantly more robust at reproducing AT maps
      between consecutive stable beats. The proposed method of global AT mapping will
      potentially enable accurate mapping of non-repetitive propagation during
      arrhythmias.

PMID- 24110052
TI  - Image-based analysis of droplets in microfluidics.
AB  - In order to design a microfluidic device that can produce monodispersed
      encapsulated enzymes as droplets, it is essential to be able to evaluate the
      system during its development. An automated method to determine the size of the
      droplets as well as a method to tag and track droplets as they move in the system
      is desirable for system evaluation. We apply the Hough transform for circles to
      determine droplet size. Most of the droplets in the images are detected, and the
      best results are obtained at 20x magnification. We also test the ability of the
      ImageJ 'particle tracker' plugin to determine the behaviour of the droplets as
      they move in microfluidic systems. It is effective in tracking droplets that
      travel less than 50 pixels between frames. 

PMID- 24110053
TI  - Functional near-infrared spectroscopy based discrimination of mental counting and
      no-control state for development of a brain-computer interface.
AB  - In this paper we propose to apply functional near-infrared spectroscopy (fNIRS)
      to measure the brain activity during mental counting and discriminate it from the
      no-control (rest) state, which could potentially lead to a two-choice brain
      computer interface (BCI) application. fNIRS is a relatively new optical brain
      imaging modality that can be used for BCI. The major advantages using fNIRS are
      its relatively low cost, safety, portability, wearability and overall ease of
      use. In the present research, five healthy subjects are asked to perform mental
      counting during the activity period. Signals from the prefrontal cortex are
      acquired using a continuous-wave imaging system. The mental counting and no
      control states are classified, using linear discriminant analysis (LDA), with an
      average accuracy of 80.6%. These classified signals can be translated into
      control commands for a two-choice BCI. These results show fNIRS to be a potential
      candidate for BCI. 

PMID- 24110054
TI  - Asymmetry brain function in auditory cortex: a functional near-infrared
      spectroscopy study.
AB  - Functional near-infrared spectroscopy (fNIRS) can measure the change of
      hemodynamic response, it enables to determine the concentration changes of oxy
      hemoglobin and deoxy-hemoglobin. The aim in this paper is to investigate the
      forms of lateralization or asymmetry brain function in auditory cortex using
      fNIRS. This technique shows good promise for assessment of asymmetry functions in
      the auditory cortex. 

PMID- 24110056
TI  - Exploration of cerebral activation using hemodynamic modality separation method
      in high-density multichannel fNIRS.
AB  - Hemodynamic modality separation (HMS) is a method for separating the functional
      near infrared spectroscopy (fNIRS) signal into the cerebral functional and
      systemic physiological components based on their difference in hemodynamic
      modalities: 1) Changes in oxyhemoglobin and deoxyhemoglobin (DeltaHbO and
      DeltaHbR) in the cerebral capillaries during neural activation negatively
      correlate with each other; 2) Other physiological hemodynamic changes originating
      from major vessels cause a positive correlation in DeltaHbO and DeltaHbR. We
      applied this simple method to a high-density multichannel (HDM) fNIRS
      measurement. In the case of functional signal detection in the parietal area of
      human adults during a single-sided finger-tapping task, conventional fNIRS data
      showed very unclear signal laterality, while the functional components separated
      by the HMS method highly localized at the contralateral area of the tapping side.
      Using the HMS method for HDM NIRS, we successfully explored cerebral activation
      in the parietal area. This is the first report that HMS method was utilized for
      the exploratory detection of cerebral activity. 

PMID- 24110055
TI  - GLM analysis of time resolved NIRS data of motor activation during different
      motor tasks.
AB  - The hemodynamic response to motor activation was investigated by time-resolved
      NIRS in healthy subjects and patients with unilateral impairment in motor
      ability. Healthy subjects performed a simple and a complex finger movement task,
      patients a handgrip task. A General Linear Model approach (GLM) was applied
      during NIRS data processing. In general, compared to the integral (continuous
      wave signal), higher significance of activation was found for the variance signal
      that selectively represents changes in the deep compartment. A discussion of GLM
      results with respect to task complexity and difficulty is provided. 

PMID- 24110057
TI  - New reconstruction technique for 3 dimensional structure in shallow layer of
      turbid medium using optical transillumination images - Attempt for reconstruction
      with limited view angle.
AB  - In transillumination imaging of an animal body with near-infrared light, the
      shallower structure appears clearer. Therefore, we can reconstruct the three
      dimensional (3D) image of the shallow structure using the transillumination
      images as the projection images. In the 3D reconstruction, it may be better to
      use the projection images of limited observation-angle range rather than those
      from 360 degrees  range. We investigated this possibility and devised a new
      technique to reconstruct the 3D image of the light absorbing structure in shallow
      region of a turbid medium. This technique is applicable to the turbid object
      without any a priori knowledge on the angular position of the absorbing
      structure. The feasibility of the proposed technique was verified in experiments.

PMID- 24110058
TI  - Study of neurovascular coupling functions for transient focal cerebral ischemia
      in rats using electrocorticography functional photoacoustic microscopy (ECoG
      fPAM).
AB  - Recently, the functional photoacoustic microscopy (fPAM) system has been proven
      to be a reliable imaging technique for measuring the total hemoglobin
      concentration (HbT), cerebral blood volume (CBV) and hemoglobin oxygen saturation
      (SO2) in single cerebral blood vessels of rats. In this study, we report for the
      first time the combination of electrocorticography (ECoG) recordings and fPAM
      (ECoG-fPAM) to investigate functional hemodynamic changes and neuro-vascular
      coupling in single cortical arterioles of rats with electrical forepaw
      stimulation after photothrombotic stroke. Because of the optical focusing nature
      of our fPAM system, photo-induced ischemic stroke targeting on single cortical
      arterioles can be easily conducted with simple adaptation. Functional cerebral
      HbT, CBV and SO2 changes associated with the induced stroke in selected
      arterioles from the anterior cerebral artery system were imaged with a 36 * 65-um
      spatial resolution. The ECoG-fPAM system complements existing imaging techniques
      and has the potential to offer a favorable tool for explicitly studying cerebral
      hemodynamics and neuro-vascular coupling in small animal models of photo-induced
      ischemic stroke. 

PMID- 24110059
TI  - Dynamics of hemoglobin states in the sensorimotor cortex during motor tasks: a
      functional near infrared spectroscopy study.
AB  - In this study, we used functional near infrared spectroscopy (fNIRS) imaging to
      investigate the independent levels of oxygenated, deoxygenated, and total
      hemoglobin (oxy-Hb, deoxy-Hb, and total-Hb, respectively) at the sensorimotor
      cortex during hand-grasping motor tasks. Our results showed that the activation
      of contralateral primary motor cortex (M1) exhibited increased oxy-Hb and reduced
      dexoy-Hb after hand grasping began. Meanwhile, the contralateral primary
      somatosensory cortex (S1) was deactivated with reductions of both oxy-Hb and
      deoxy-Hb concentration. The Hb circulation patterns indicated that the hand
      grasping demanded rapid and sufficient O2 supply at contralateral M1, which was
      achieved by the local vasodilation. The contralateral S1 presented decreased
      total-Hb via the mechanism of vasoconstriction, and maintained the local
      oxygenation level in a relatively stable state (mostly with O2 debt) to
      compensate the blood demanding at nearby M1. This study presented that fNIRS data
      can efficiently differentiate the activation of M1 from the deactivation of S1
      during motor tasks, which can provide full interpretations of hemodynamic
      response to the neuronal activation in comparison with the Blood Oxygenation
      Level Dependent signal of functional magnetic resonance imaging. 

PMID- 24110060
TI  - Cerebral blood flow changes during rat cardiopulmonary bypass and deep
      hypothermic circulatory arrest model: a preliminary study.
AB  - Cardiopulmonary bypass (CPB) and deep hypothermic circulatory arrest (DHCA) are
      important techniques often used in complex cardiac surgery for neonates and
      infants heart diseases. Cerebral blood flow (CBF) serves as an important
      physiological parameter and provides valuable hemodynamic information during the
      surgery. Laser speckle imaging (LSI), as an optical imaging technique, can
      provide full-field CBF information with a high spatiotemporal resolution. In this
      preliminary study, we acquired the real-time CBF images with a self-developed
      miniaturized head-mounted LSI system during the whole CPBillHCA rat model.
      Relative CBF velocity in veins and arteries in bilateral hemispheres dropped
      significantly during cooling period and reached to nearly zero during arrest
      period (n = 5). More interestingly, two rats showing more dramatic CBF variations
      in veins than in arteries during cooling period exhibited severe cerebral edema
      after surgery. The real-time full-field CBF imaging during the CPBillHCA surgery
      could add more insights into the operation and be utilized to study the surgical
      protocols with the ultimate goal ofreducing neurologic injury after surgery. 

PMID- 24110061
TI  - In vivo time-resolved DOT measurement and image reconstruction of human forearm
      under exercises.
AB  - In vivo measurement of time-resolved diffuse optical tomography (TR-DOT) were
      performed for human forearms under the exercises. The DOT images of oxygenation
      state were reconstructed, and the activities of the inner muscles were assessed. 

PMID- 24110062
TI  - Hemodynamic effects of pressure-volume relation in the atrial contraction model
      on the total artificial heart using centrifugal blood pumps.
AB  - Hemodynamic effects of atrial contraction with centrifugal pump type total
      artificial heart is unknown. In this study, we simulated an atrial contraction in
      a mock model. By the driving condition with higher pressure in the mock atrial
      model, the load during atrial contraction increased. Based on these findings, we
      examined atrial contraction in the animal using adult goats. Prior to the
      measurement, we installed a centrifugal-type ventricular assist device (VADs),
      and then clamped both ventricles. We measured the hemodynamic data without
      ventricular contractile functions in order to obtain the effect of atrial
      contraction on hemodynamics under the condition of the total artificial heart
      (TAH) circulatory support model. We could estimate the heart rate by revolution
      number and voltage of pumps. There might be a possibility that we could regulate
      autonomic nervous response with the control of cardiac output. 

PMID- 24110063
TI  - Effects of hyperglycemia on variability of RR, QT and corrected QT intervals in
      Type 1 diabetic patients.
AB  - In this study, we evaluated the effects of hyperglycemia on the variability of RR
      (HRV), QT interval variability (QTV) and corrected QT interval variability (QTcV)
      during hyperglycemic and non-hyperglycemic conditions in six Type 1 diabetic
      patients at nights. The aim of this study was to investigate the association of
      high blood glucose levels with autonomic modulation of heart rate and variation
      in ventricular repolarization. Blood glucose level (BGL) threshold for defining
      hyperglycemia state was set at 8.33 mmol/l. Variability of RR, QT and corrected
      QT intervals during hyperglycemic and non-hyperglycemic were quantified using
      time and frequency domain measures. Hypomon(r) device was used to monitor ECG
      signals and acquire RR and QT intervals in Type 1 diabetic patients overnight.
      The results indicated that time and frequency domain HRV variables were
      significantly decreased under hyperglycemic condition and inversely correlated
      with BGL. QTV parameters also reduced when BGL increased and time domain measures
      of QTV were inversely associated with BGL. Variability in QTc interval was much
      less than in the QT interval and demonstrated a lower SDNN and LF power. We
      concluded that certain components of HRV, time-domain measures of QTV and QTc but
      not QTcV are strongly correlated to high blood glucose levels and can be good
      markers to identify hyperglycemic events in T1DM. 

PMID- 24110064
TI  - An algorithm to improve the estimation accuracy of a non-invasive method for
      cardiac output measurement based on prolonged expiration.
AB  - Cardiac output (CO) monitoring is important in the hemodynamic management of
      critically ill patients. In a previous study, a novel non-invasive technique for
      CO monitoring based on prolonged expiration was proposed. The novel method showed
      good agreement with thermodilution on stable mechanically ventilated patients;
      unstable patients were excluded. The aim of this study is to improve the outcome
      of the above mentioned method on hemodynamic unstable patients, requiring
      vasoactive medications, and showing marked cardiogenic oscillations on waveforms
      related to expired gases. This prospective study has been carried out on three
      cardiac surgery patients; eighteen CO measurements were performed on each
      patient, and these values were compared with data obtained by thermodilution. The
      designed and tested algorithm allowed to reach a good agreement between CO
      measured by our method and by thermodilution (e.g., the mean percentage
      differences were 4%, 11% and 3%). Even though further validation is necessary,
      the results are quite promising and the adopted solution appears to allow the
      suitability of the prolonged expiration method also on unstable patients.

PMID- 24110065
TI  - Simultaneous analysis system for blood pressure and flow using
      photoplethysmography and ultrasonic-measurement-integrated simulation.
AB  - We developed a simultaneous analysis system for blood pressure and flow using
      photoplethysmography and ultrasonic-measurement-integrated simulation. The
      validity of the system was confirmed by analysis of blood flow field in a carotid
      artery and corresponding wave intensity (WI) values. 

PMID- 24110066
TI  - Design, manufacture and in-vitro evaluation of a new microvascular anastomotic
      device.
AB  - INTRODUCTION: Many microvascular anastomoses have been proposed for use with
      physical assisted methods, such as cuff, ring-pin, stapler, clip to the
      anastomose blood vessel. The ring-pin type anastomotic device (e.g., 3M
      Microvascular Anastomotic System) is the most commonly used worldwide because the
      anastomotic procedure can be conducted more rapidly and with fewer traumas than
      using sutures. However, problems including vessel leakage, ring slippage, high
      cost and high surgical skill demand need to be resolved. The aim of this study is
      to design and manufacture a new anastomotic device for microvascular anastomosis
      surgery and validate the device functions with in-vitro testing. METHODS: The new
      device includes one pair of pinned rings and a set of semi-automatic flap
      apparatus designed and made using computer-aided design / computer-aided
      manufacture program. A pair of pinned rings was used to impale vessel walls and
      establish fluid communication with rings joined. The semi-automatic flap
      apparatus was used to assist the surgeon to invert the vessel walls and impale
      onto each ring pin, then turning the apparatus knob to bring the rings together.
      The device was revised until it became acceptable for clinical requires. An in
      vitro test was performed using a custom-made seepage micro-fluid system to detect
      the leakage of the anastomotic rings. The variation between input and output flow
      for microvascular anastomoses was evaluated. RESULTS: The new microvascular
      anastomotic device was convenient and easy to use. It requires less time than
      sutures to invert and impale vessel walls onto the pinned rings using the semi
      automatic flap apparatus. The in-vitro test data showed that there were no tears
      from the joined rings seam during the procedures. CONCLUSIONS: The new
      anastomotic devices are effective even with some limitations still remaining.
      This device can be helpful to simplify the anastomosis procedure and reduce the
      surgery time.

PMID- 24110067
TI  - Blood pressure monitor with a position sensor for wrist placement to eliminate
      hydrostatic pressure effect on blood pressure measurement.
AB  - Accurate measurement of blood pressure at wrist requires the heart and wrist to
      be kept at the same level to avoid the effects of hydrostatic pressure. Although
      a blood pressure monitor with a position sensor that guides appropriate forearm
      angle without use of a chair and desk has already been proposed, a similar
      functioning device for measuring upper arm blood pressure with a chair and desk
      is needed. In this study, a calculation model was first used to explore design of
      such a system. The findings were then implemented into design of a new blood
      pressure monitor. Results of various methods were compared. The calculation model
      of the wrist level from arthrosis angles and interarticulars lengths was
      developed and considered using published anthropometric dimensions. It is
      compared with 33 volunteer persons' experimental results. The calculated
      difference of level was -4.1 to 7.9 (cm) with a fixed chair and desk. The
      experimental result was -3.0 to 5.5 (cm) at left wrist and -2.1 to 6.3(cm) at
      right wrist. The absolute difference level equals +/-4.8 (mmHg) of blood pressure
      readings according to the calculated result. This meets the AAMI requirements for
      a blood pressure monitor. In the conclusion, the calculation model is able to
      effectively evaluate the difference between the heart and wrist level. Improving
      the method for maintaining wrist to heart level will improve wrist blood pressure
      measurement accuracy when also sitting in the chair at a desk. The leading angle
      of user's forearm using a position sensor is shown to work for this purpose. 

PMID- 24110069
TI  - Noninvasive diagnosis of coronary artery disease using two parameters extracted
      in an extrema circle of magnetocardiogram.
AB  - Magnetocardiography (MCG) is a complementary or alternative tool for noninvasive
      detection of coronary artery disease (CAD). The effectiveness of the tool for CAD
      diagnosis is generally evaluated by statistical analysis. In this study, we
      present a new method for screening CAD, in which two parameters including the
      curvature of magnetic field zero line and the area ratio of the extrema circle
      are extracted in magnetic field maps. 50 normal and 28 CAD subjects, whose
      signals were recorded by a 4-channel superconducting quantum interference device
      system, are analyzed with this method. The statistical results show a sensitivity
      and specificity of 71.4% and 72.0% respectively. 

PMID- 24110070
TI  - Wearable and superhydrophobic hardware for ambulatory biopotential acquisition.
AB  - Wearable monitoring devices are a promising trend for ambulatory and real time
      biosignal processing, because they improve access and coverage by means of
      comfortable sensors, with real-time communication via mobile networks. In this
      paper, we present a garment for ambulatory electrocardiogram monitoring, a smart
      t-shirt with a textile electrode that conducts electricity and has a coating
      designed to preserve the user's hygiene, allowing long-term mobile measurements.
      Silicon dioxide nanoparticles were applied on the surface of the textile
      electrodes to preserve conductivity and impart superhydrophobic properties. A
      model to explain these results is proposed. The best result of this study is
      obtained when the contact angles between the fluid and the fabric exceeded 150
      degrees , while the electrical resistivity remained below 5 Omega.cm, allowing an
      acquisition of high quality electrocardiograms in moving patients. Thus, this
      tool represents an interesting alternative for medium and long-term measurements,
      preserving the textile feeling of clothing and working under motion conditions. 

PMID- 24110071
TI  - ActimedARM - design of a wearable system to monitor daily actimetry.
AB  - We developed a low power kinematic sensor, ActimedARM, incorporating three-axis
      accelerometer and magnetometer, a microcontroller ARM3, a ZigBee wireless
      communication and MUSD memory storage. With embedded algorithms it can detect in
      real time the postures of the subject. A preliminary assessment conducted on 12
      subjects reached a 97% correct classification rate. The device exhibits 32 days
      of autonomy on a 3600 mAh capacity battery, which makes it convenient for field
      experiments in true daily life. 

PMID- 24110072
TI  - A reliable medium access mechanism based on priorities for wireless body sensor
      networks.
AB  - Wireless body sensor networks (WBSN) provide health related information for
      monitoring or professional analysis by collecting various signals of human body
      or environment information with sensors. But different data acquired in many
      applications have different transmission requirements. The dropping of life
      critical messages could possibly create life threatening results if the network
      is not reliable. To improve the reliability this paper proposes a novel reliable
      medium access mechanism (RMAM) which guarantees transmission of data with
      different priorities in less delay and energy consumption. The mechanism is
      designed and evaluated by Castalia. The improved performances of latency, packets
      breakdown and energy consumption are analyzed and depicted with comparison. 

PMID- 24110073
TI  - Columnar transmitter based wireless power delivery system for implantable device
      in freely moving animals.
AB  - A wireless power delivery system is developed to deliver electrical power to the
      neuroprosthetic devices that are implanted into animals freely moving inside the
      cage. The wireless powering cage is designed for long-term animal experiments
      without cumbersome wires for power supply or the replacement of batteries. In the
      present study, we propose a novel wireless power transmission system using
      resonator-based inductive links to increase power efficiency and to minimize the
      efficiency variations. A columnar transmitter coil is proposed to provide lateral
      uniformity of power efficiency. Using this columnar transmitter coil, only 7.2%
      efficiency fluctuation occurs from the maximum transmission efficiency of 25.9%.
      A flexible polymer-based planar type receiver coil is fabricated and assembled
      with a neural stimulator and an electrode. Using the designed columnar
      transmitter coil, the implantable device successfully operates while it moves
      freely inside the cage. 

PMID- 24110074
TI  - Implantable image sensor based on intra-brain image transmission.
AB  - We developed and fabricated a micro-imager based on wireless intra-brain
      communication using conductive property of living tissues. An pixel array, analog
      to-digital converter and transmitter are integrated on a single chip. The
      dimensions of the chip are 1 mm * 1mm * 0.15 mm. We demonstrate wireless image
      transmission through phosphate buffer saline as a brain phantom. 

PMID- 24110075
TI  - Development of an implantable wireless ECoG 128ch recording device for clinical
      brain machine interface.
AB  - Brain Machine Interface (BMI) is a system that assumes user's intention by
      analyzing user's brain activities and control devices with the assumed intention.
      It is considered as one of prospective tools to enhance paralyzed patients'
      quality of life. In our group, we especially focus on ECoG (electro-corti-gram)
      BMI, which requires surgery to place electrodes on the cortex. We try to implant
      all the devices within the patient's head and abdomen and to transmit the data
      and power wirelessly. Our device consists of 5 parts: (1) High-density multi
      electrodes with a 3D shaped sheet fitting to the individual brain surface to
      effectively record the ECoG signals; (2) A small circuit board with two
      integrated circuit chips functioning 128 [ch] analogue amplifiers and A/D
      converters for ECoG signals; (3) A Wifi data communication & control circuit with
      the target PC; (4) A non-contact power supply transmitting electrical power
      minimum 400[mW] to the device 20[mm] away. We developed those devices, integrated
      them, and, investigated the performance. 

PMID- 24110076
TI  - Downsizing of coreless coils for transcutaneous energy transmission in
      implantable devices - improvement of coupling factor and efficiency between
      coils.
AB  - Transcutaneous energy transmission is useful for improving patient quality of
      life and for supplying energy to implantable devices noninvasively. To supply
      highly efficient energy transmission through the skin, it is necessary to
      increase the coupling factor between the coils and increase the inductance of
      each coil. In this study, the optimal shape required for the coils to increase
      the coupling factor was investigated. 

PMID- 24110077
TI  - A novel wireless power and data transmission AC to DC converter for an
      implantable device.
AB  - This article presents a novel AC to DC converter implemented by standard CMOS
      technology, applied for wireless power transmission. This circuit combines the
      functions of the rectifier and DC to DC converter, rather than using the
      rectifier to convert AC to DC and then supplying the required voltage with
      regulator as in the transitional method. This modification can reduce the power
      consumption and the area of the circuit. This circuit also transfers the loading
      condition back to the external circuit by the load shift keying(LSK), determining
      if the input power is not enough or excessive, which increases the efficiency of
      the total system. The AC to DC converter is fabricated with the TSMC 90nm CMOS
      process. The circuit area is 0.071mm(2). The circuit can produce a 1V DC voltage
      with maximum output current of 10mA from an AC input ranging from 1.5V to 2V, at
      1MHz to 10MHz. 

PMID- 24110079
TI  - A study on transmission characteristics and specific absorption rate using
      impedance-matched electrodes for various human body communication.
AB  - Human body communication (HBC) is a new communication technology that has
      presented potential applications in health care and elderly support systems in
      recent years. In this study, which is focused on a wearable transmitter and
      receiver for HBC in a body area network (BAN), we performed electromagnetic field
      analysis and simulation using the finite difference time domain (FDTD) method
      with various models of the human body. Further we redesigned a number of
      impedance-matched electrodes to allow transmission without stubs or transformers.
      The specific absorption rate (SAR) and transmission characteristics S21 of these
      electrode structures were compared for several models. 

PMID- 24110078
TI  - Development of distance-selective nerve recruitment for subcortical brain mapping
      by controlling stimulation waveforms.
AB  - During brain surgery, it is important to determine the functional brain area and
      cortico-cortical pathways so as to keep them intact and preserve patients'
      quality of life. Cortical and subcortical brain mappings are techniques that
      deliver direct current stimulation to the brain surface and beneath gray matter
      to identify the brain area and nerve fibers related to higher-order functions.
      However, because of the non-selective effect of conventional electrical
      stimulation methods, it has been difficult to obtain precise spatial distribution
      of nerve fibers in the subcortical region. We investigated the electrical
      stimulation of subcortical mapping to evaluate axon-to-electrode distance
      selectivity. It was clarified that a conventional rectangular biphasic pulse
      activates axons non-selectively. We propose double exponential waveforms and show
      that they can recruit targeted fibers and change the location of a target by
      manipulating stimulus intensity. These results suggest the usefulness of
      introducing distance-selective stimulation into subcortical brain mapping. 

PMID- 24110080
TI  - Development of electromagnetic phantom at low-frequency band.
AB  - This paper describes the development of a human electrical phantom at a low
      frequency band. The conventional highly hydrous electromagnetic phantom does not
      mimic the electrical properties of a living body. The electrical properties of
      the newly developed phantom, by adding a carbon microcoil (CMC) and NaCl to the
      conventional phantom, are in good agreement with those of a living body. In
      addition, the electrical properties of the phantom with a CMC and twice the
      amount of NaCl added are evaluated at frequency bands above 300 MHz, similar to
      the conventional highly hydrous gel phantom. The results show that the newly
      developed phantom can effectively function in the conventional target frequency
      band by a simple mechanism. 

PMID- 24110081
TI  - 3D simulation of platelet aggregation in cryosurgery.
AB  - In cryosurgery for cancer treatment, cells are injured not only by freezing but
      also by vascular stasis. The vascular stasis caused by thrombosis necrotizes the
      surrounding non-targeted cells due to the lack of oxygen and nourishment.
      Inhibition of thrombus formation, which is the former phase of the vascular
      stasis, is required to prevent damaging normal cells around a tumorDForegoing
      studies simulated platelet aggregation based on distance between platelets.
      However, in cryosurgery, temperature dependency of blood-clotting factors'
      activity is required to be considered. The authors constructed a three
      dimensional model consisting of vascular and extra- vascular tissues, and
      simulated heat transform and platelet aggregation. Heat transform was analyzed by
      boundary fitted coordinates method, and platelet aggregation was analyzed by
      particle method. The probability of bonding between platelets is derived from
      chemical reaction kinetics. The results showed larger size of simulated thrombus
      on higher temperature. The simulation with varied temperature around destructed
      area showed platelet aggregation depending on temperature. 

PMID- 24110082
TI  - Hemodynamics at the ostium of cerebral aneurysms with relation to post-treatment
      changes by a virtual flow diverter: a computational fluid dynamics study.
AB  - Computational fluid dynamics (CFD) techniques have been refined for modeling the
      hemodynamics in cerebral aneurysms. Recent interest has focused on understanding
      hemodynamic changes by treatment with a flow diverter (FD), i.e. a stent with a
      dense metal mesh which is placed across the ostium to divert the majority of flow
      away from the aneurysm. Potential complications include remnant inflow jets but,
      more seriously, aneurysm hemorrhage. For optimization of treatment outcome, a
      better understanding of the effects caused by the FD would be beneficial. In
      particular, pressure and velocity distributions at the aneurysm ostium are of
      interest, as they will be directly affected by the FD which in turn will
      influence post-treatment hemodynamics inside the aneurysm. Here, we report the
      results of a CFD study investigating the relationship between pre-treatment and
      post-treatment velocities, pressures and wall shear stresses (WSS) in the
      aneurysm with corresponding hemodynamic conditions at the aneurysm ostium prior
      to treatment. The study was carried out using a dedicated CFD prototype which
      allows modeling the effects of a virtual FD integrated into patient-specific
      geometries utilizing Darcy's law. Velocities and WSS were reduced in all cases
      post FD treatment, pressure increased in one case. Heterogeneous distributions of
      the velocity magnitude were found at the ostium with focal maxima indicating
      potential risk zones for remnant inflow jets into the aneurysms. Pressures at the
      ostium correlated with pressure changes inside the aneurysm which could become a
      pre-treatment indicator for the evaluation of the suitability of a particular
      aneurysm for FD treatment. 

PMID- 24110083
TI  - Study of thermal effect on breast tumor metabolism and growth using metabonomics.
AB  - In this study, the biological effects of long-term mild hyperthermia treatment on
      tumor metabolism and growth were investigated using 4T1 murine mammary carcinoma,
      a common animal model of metastatic breast cancer. Periodic thermal treatment (12
      hours per day) was applied to tumors and carried out for 3 days, 7 days, 14 days,
      and 21 days, respectively. The metabolites of tumor tissues were analyzed by gas
      chromatography-mass spectrometry. The results showed that the growth rate of
      thermally treated tumors was inversely related to the abundance of long chain
      fatty acids and acyl glycerols identified in tumor tissues. In the first two
      weeks, the growth of thermally treated tumors was significantly inhibited, while
      there was an obvious accumulation of long chain fatty acids and acyl glycerols in
      tumor tissues. In the third week, the thermally treated tumors adapted to the
      thermal environment and started to regrow, while the abundance of long chain
      fatty acids and acyl glycerols decreased in the tumor tissues. These observations
      suggested that the blockade of long chain fatty acid synthesis during mild
      hyperthermia treatment of tumors could improve the long-term treatment effect by
      limiting the supply of substance and energy for tumor re-growth. 

PMID- 24110084
TI  - A simulator for mixed Doppler ultrasound signals from pulsatile blood flow and
      vessel wall with mild stenosis.
AB  - A novel computer simulator to generate mixed Doppler ultrasound signals from the
      pulsatile blood flow and vessel wall with mild stenosis is presented in this
      paper. In-phase and quadrature Doppler blood flow signals are generated using
      cosine-superposed components modulated by a spectrogram estimated from velocity
      profile. Meanwhile,Doppler signals echoed from bidirectional moving walls are
      generated with the input waveforms of the wall velocities. Finally, the Doppler
      signals determined above are summed respectively to yield the combined Doppler
      signals in terms of given sample volume shape. The experimental results show that
      the proposed simulator generates mixed Doppler signals with the characteristics
      similar to those found in practice, and could be an useful experimental data
      source for evaluating the performance of wall filters. 

PMID- 24110085
TI  - Fetal electrocardiogram enhancement in abdominal recordings: recording setup
      analysis.
AB  - The fetal electrocardiogram (fECG) obtained from the abdominal signals, to
      monitor the wellbeing of the fetus, is a weak signal, recorded by placing
      electrodes on the maternal abdomen surface. When recording the abdominal fECG,
      the main problem is to separate the fECG from the background noise, including the
      maternal electrocardiogram (mECG) and/or the power line interference (PLI), this
      leading to an improved fECG signal to noise ratio (SNR). This paper proposes and
      evaluates three types of recording configurations, having different reference
      location, and analyzes the performance of each recording setup, based on the
      corresponding SNRs, quantitatively evaluated. The fECG extraction is carried out
      in order to evaluate the performance of each proposed configuration. 

PMID- 24110086
TI  - Feature extraction and classification of sEMG signals applied to a virtual hand
      prosthesis.
AB  - This paper presents the classification of motor tasks, using surface
      electromyography (sEMG) to control a virtual prosthetic hand for rehabilitation
      of amputees. Two types of classifiers are compared: k-Nearest Neighbor (k-NN) and
      Bayesian (Discriminant Analysis). Motor tasks are divided into four groups
      correlated. The volunteers were people without amputation and several analyzes of
      each of the signals were conducted. The online simulations use the sliding window
      technique and for feature extraction RMS (Root Mean Square), VAR (Variance) and
      WL (Waveform Length) values were used. A model is proposed for reclassification
      using cross-validation in order to validate the classification, and a
      visualization in Sammon Maps is provided in order to observe the separation of
      the classes for each set of motor tasks. Finally, the proposed method can be
      implemented in a computer interface providing a visual feedback through an
      virtual hand prosthetic developed in Visual C++ and MATLAB commands. 

PMID- 24110087
TI  - In-vitro quantification of rat liver viscoelasticity with shear wave dispersion
      ultrasound vibrometry.
AB  - As a new imaging method for tissue mechanical properties, ultrasound elastography
      has always been the research focus in the field of medical ultrasound imaging
      ever since it has been proposed. This paper developed an ultrasound
      viscoelasticity measurement system based on shear wave dispersion ultrasound
      vibrometry (SDUV). This system applied acoustic radiation force to excite
      harmonic vibration in soft tissue. The propagation of the shear wave induced by
      the vibration was detected and the tissue viscoelasticity properties were
      calculated. Based on this system, rat livers were measured in vitro. The results
      shows that the system can measure the viscoelasticity reliably, offering a
      potential alternative to diagnosis of liver fibrosis. 

PMID- 24110088
TI  - An algorithm for assessment of inflow and washout of optical contrast agent to
      the brain by analysis of time-resolved diffuse reflectance and fluorescence
      signals.
AB  - In optical measurements of the brain oxygenation and perfusion the problem of
      contamination of the signals with the components related to the extracerebral
      tissues remains an obstacle limiting clinical applicability of the technique. In
      this paper we present an algorithm allowing for derivation of signals related to
      the changes in absorption in the intracerebral tissues based on analysis of time
      resolved diffuse reflectance and fluorescence. The proposed method was validated
      in series of Monte Carlo simulations in which inflow and washout of an optical
      contrast agent into the two-layered human head model was considered. It was shown
      that the decomposed intracerebral component of the signal can be derived with
      uncertainty of about 5%. This result suggests that the method proposed can be
      applied in improved estimation of brain perfusion parameters based on the bolus
      tracking technique. 

PMID- 24110089
TI  - Modelling muscle spindle dynamics for a proprioceptive prosthesis.
AB  - Muscle spindles are found throughout our skeletal muscle tissue and continuously
      provide us with a sense of our limbs' position and motion (proprioception). This
      paper advances a model for generating artificial muscle spindle signals for a
      prosthetic limb, with the aim of one day providing amputees with a sense of
      feeling in their artificial limb. By utilising the Opensim biomechanical
      modelling package the relationship between a joint's angle and the length of
      surrounding muscles is estimated for a prosthetic limb. This is then applied to
      the established Mileusnic model to determine the associated muscle spindle firing
      pattern. This complete system model is then reduced to allow for a
      computationally efficient hardware implementation. This reduction is achieved
      with minimal impact on accuracy by selecting key mono-articular muscles and
      fitting equations to relate joint angle to muscle length. Parameter values
      fitting the Mileusnic model to human spindles are then proposed and validated
      against previously published human neural recordings. Finally, a model for
      fusimotor signals is also proposed based on data previously recorded from reduced
      animal experiments. 

PMID- 24110090
TI  - A new approach to improve the quality of biosensor signals using Fast Independent
      Component Analysis: feasibility study using EMG recordings.
AB  - The proposed signal processing technique uses Fast Independent Component Analysis
      (ICA) algorithm to improve the quality of the original biosensors recordings,
      which can be used as valuable pre-processing technique such as cross talk
      removal, artefact reduction etc. Initially, the ill conditioned original surface
      Electromyography (sEMG) recordings were separated using ICA methods and later
      they were reconstructed using modified un-mixing matrix. The simulation results
      showed huge improvement of the original recorded signal after reconstruction. The
      proposed method has potential applications in various biomedical signal
      processing techniques. 

PMID- 24110091
TI  - Ultrasonic guided waves dispersion reversal for long bone thickness evaluation: a
      simulation study.
AB  - It has been shown that ultrasonic guided waves have great potentials for long
      cortical bone evaluation. However, due to the multimodal dispersion, the received
      signals usually contain several mixed guided modes, which highly complicates the
      mode separation and signal processing. In the study, we showed that the use of
      dispersion reversal excitation allows the self-compensation of the dispersive
      modes in the long cortical bone. Two-dimension finite-difference time-domain (2D
      FDTD) method was employed to simulate the propagation of two fundamental guided
      modes, symmetrical S0 and anti-symmetrical A0, in the long cortical bones. It was
      demonstrated that the pulse-like modes of S0 and A0 can be detected under the
      dispersion reversal excitations. The simulations also illustrated that the
      proposed dispersion reversal method can be used to evaluate the cortical
      thickness. Results are promising for the application of dispersion reversal
      method in ultrasonic assessment of the long cortical bone. 

PMID- 24110092
TI  - Temporal and steady state acoustic field in a cell culture well: simulation.
AB  - The present study was to understand the true power irradiated to the cell line
      cultured on a culture well, in relation to the nominal power from ultrasonic
      transducer, and to characterize the temporal variations of the acoustic pressure
      exerted on the cell. Numerical simulation was carried out for a typical culture
      well exposed to 1 MHz continuous ultrasound generated by a circular transducer
      contact underneath the well. The results showed that the ultrasonic pressure
      exposed to the cell layer in the well was 6.7 times larger than the nominal
      pressure of the ultrasonic transducer. The ultrasonic pressure in the transient
      period rose rapidly and was widely variable, and the temporal peak was even
      greater than that of the steady state period. This suggests that the cells
      undergo characteristically different ultrasonic exposure between the transient
      and the steady state period. 

PMID- 24110093
TI  - Measuring chest circumference change during respiration with an electromagnetic
      biosensor.
AB  - In this paper, an off-the-shelf DC motor is modified into a chest belt and used
      to successfully measure circumference change on a mechanical chest model, while
      simultaneously harvesting significant power. Chest circumference change can
      provide information on tidal volume, which is vital in assessing lung function.
      The chest circumference change is calculated from the motor's voltage output.
      Calculated values are within 0.95mm of measured circumference changes, with a
      standard deviation of 0.37mm. The wearable motor can also harvest at least 29.4uW
      during normal breathing. 

PMID- 24110094
TI  - Respiratory-cycle related analysis of the EEG-spectrum during sleep: a healthy
      population study.
AB  - Recent research has shown the EEG's spectral changes that occur in synchrony with
      the respiratory-cycle. During wakefulness, and for healthy subjects it is
      reported that the EEG power in several frequency bands changes between the
      expiratory and inspiratory phases. For sleep-disordered breathing (SDB) patients,
      it is reported that the amplitude of changes in normalized EEG power (referred to
      as respiratory-cycle related EEG changes RCREC) within a respiratory-cycle
      decreases after a successful intervention to alleviate the SDB condition. In this
      paper, we focus on analyzing the changes in the sleep's EEG spectrum related to
      the respiratory-cycle for a healthy population comprising 39 subjects. For 3
      sleep stages (N2, N3, REM), 6 EEG channels, and 7 frequency bands, two types of
      EEG spectral analyzes were considered: 1) the ratio between the EEG power during
      expiration and that during inspiration, and 2) the RCREC. For the first type of
      analysis and at the population level, no statistically significant difference was
      found between the EEG power during expiration and that during inspiration. For
      the second type of analysis, the RCREC for all conditions is at a level that is
      statistically significantly larger than 0.1. The latter being the value at which
      the RCREC decreased after successful SDB intervention.

PMID- 24110095
TI  - A pipeline VLSI design of fast singular value decomposition processor for real
      time EEG system based on on-line recursive independent component analysis.
AB  - This paper presents a pipeline VLSI design of fast singular value decomposition
      (SVD) processor for real-time electroencephalography (EEG) system based on on
      line recursive independent component analysis (ORICA). Since SVD is used
      frequently in computations of the real-time EEG system, a low-latency and high
      accuracy SVD processor is essential. During the EEG system process, the proposed
      SVD processor aims to solve the diagonal, inverse and inverse square root
      matrices of the target matrices in real time. Generally, SVD requires a huge
      amount of computation in hardware implementation. Therefore, this work proposes a
      novel design concept for data flow updating to assist the pipeline VLSI
      implementation. The SVD processor can greatly improve the feasibility of real
      time EEG system applications such as brain computer interfaces (BCIs). The
      proposed architecture is implemented using TSMC 90 nm CMOS technology. The sample
      rate of EEG raw data adopts 128 Hz. The core size of the SVD processor is 580*580
      um(2), and the speed of operation frequency is 20MHz. It consumes 0.774mW of
      power during the 8-channel EEG system per execution time. 

PMID- 24110096
TI  - Microwave technology for localization of traumatic intracranial bleedings-a
      numerical simulation study.
AB  - Traumatic brain injury (TBI) is a major public health problem worldwide.
      Intracranial bleedings represents the most serious complication of TBI and need
      to be surgically evacuated promptly to save lives and mitigate injury. Microwave
      technology (MWT) is promising as a complement to computed tomography (CT) to be
      used in road and air ambulances for early detection of intracranial bleedings. In
      this study, we perform numerical simulations to investigate if a classification
      algorithm based on singular value decomposition can distinguish between bleedings
      at different positions adjacent to the skull bone for a similar but simplified
      problem. The classification accuracy is 94-100% for all classes, a result that
      encourages us to pursue our efforts with MWT for more realistic scenarios. This
      indicates that MWT has potential for localizing a detected bleeding, which would
      increase the diagnostic value of this technique. 

PMID- 24110097
TI  - Automated analgesic drugs delivery guided by vagal tone evaluation: interest of
      the Analgesia Nociception Index (ANI).
AB  - Analgesic drugs delivery optimization constitutes one of the main objectives of
      modern anesthesia. Indeed, their over or under determination constitutes a risk
      for anesthetized patient in terms of hemodynamic reactivity or post-operative
      hyperalgesia. Nowadays, new physiological indexes allow anesthesiologists to
      evaluate the balance between the analgesia level and the noxious stimulus
      importance. ANI is an index related to the autonomic nervous system activity
      based on heart rate variability analysis. Its ability for the analgesia /
      nociception balance evaluation has been established bringing evidences about its
      helpfulness for analgesic drug delivery. In this article, we describe a device
      for automatic analgesic drugs administration based on the ANI evolution during
      surgical procedures under general anesthesia. We hypothesized that such a device
      could improve the quality and safety of anesthesia by reducing adverse
      cardiovascular events and delivered analgesic drugs doses. 

PMID- 24110098
TI  - BioSigPlot: an opensource tool for the visualization of multi-channel biomedical
      signals with Matlab.
AB  - This paper presents a Matlab-based software (MathWorks inc.) called BioSigPlot
      for the visualization of multi-channel biomedical signals, particularly for the
      EEG. This tool is designed for researchers on both engineering and medicine who
      have to collaborate to visualize and analyze signals. It aims to provide a highly
      customizable interface for signal processing experimentation in order to plot
      several kinds of signals while integrating the common tools for physician. The
      main advantages compared to other existing programs are the multi-dataset
      displaying, the synchronization with video and the online processing. On top of
      that, this program uses object oriented programming, so that the interface can be
      controlled by both graphic controls and command lines. It can be used as EEGlab
      plug-in but, since it is not limited to EEG, it would be distributed separately.
      BioSigPlot is distributed free of charge (http://biosigplot.sourceforge.net),
      under the terms of GNU Public License for non-commercial use and open source
      development. 

PMID- 24110099
TI  - Arterial pressure fractality is highly dependent on wave reflection.
AB  - Wave reflection is an important factor that influences pressure wave morphology
      and becomes more significant with aging, when cardiovascular risk increases. A
      pressure wave, measured at any location in the arterial tree, can be decomposed
      into its forward and backward components and depends on the corresponding
      amplitude and shifting time delays. Fractal dimension (FD) quantifies the time
      series complexity defined by its geometrical representation. OBJECTIVE: The aim
      of this study was to evaluate the arterial pressure and diameter time series in
      order to assess the relationship between wave reflection and arterial pressure
      fractal dimension (FD). METHODS: Simultaneous aortic pressure and diameter were
      measured in 14 conscious dogs. A pair of ultrasonic crystals, a pressure
      microtransducer and a pneumatic cuff occluder were positioned in the upper third
      of the descending aorta. RESULTS: Total reflection induced by the occlusion
      maneuver decreased FD concomitant to the aortic stiffening. CONCLUSION: Arterial
      pressure fractality is highly dependent on wave reflection.

PMID- 24110100
TI  - A new mechanical index for gauging the human bioeffects of low frequency
      ultrasound.
AB  - Low frequency ultrasound has a diverse set of industrial and medical applications
      ranging from high power industrial ultrasound equipment through to various
      therapeutic medical applications. In recent years, several speech interface
      applications have also been developed which exploit the low ultrasonic frequency
      region to augment human-computer interfacing. These devices tend to operate just
      above the threshold of human hearing where signals can be generated and detected
      using off-the-shelf audio hardware components. Mechanical index has long been one
      of the main criteria used for determining safety limits for human exposure to
      ultrasound, however it is known to be inaccurate below about 500 kHz. This paper
      revisits the mathematical and physical foundations of the mechanical index, in
      particular transient cavitation, and applies these to the low-frequency
      ultrasound region. Simulations are performed to evaluate the effects on both
      blood and water. From the results, a new mechanical index formulation is
      proposed, which extends down to significantly lower frequencies. The aim is to
      provide a gauge for determining bio-effects of emerging and future low frequency
      ultrasonic applications operating around 20 kHz to 100 kHz. 

PMID- 24110101
TI  - Effect of using ECG derived respiration (EDR) signal in linear parametric QT-RR
      modeling.
AB  - Linear parametric modeling techniques are widely used for modeling the short term
      QT-RR interaction to explore the factors (i.e. heart rate variability, Autonomic
      Nervous system) controlling ventricular repolarisation variability. Recent
      studies established that respiration also has important effect on the ventricular
      repolarisation process like it has on the heart rate variability. So for the
      clear understanding of cardiac regulations, respiration signal should be
      considered for modeling the QT-RR dynamics. Due to several problems in collecting
      original respiration signal using the traditional recording devices that measure
      the nasal air flow or abdominal or chest pressure, a lot of research has been
      done to extract respiration information from the ECG signal called the ECG
      derived respiration (EDR). In this study we verify the use of EDR signal as a
      surrogate of original respiratory signal in modeling QT-RR interaction. We
      collect 10 young subjects' ECG and respiration signal from Fantasia database. We
      developed linear parametric autoregressive model with multiple exogenous inputs
      with an autoregressive noise term and check the model performance by using
      original respiration and EDR signal and found statistically similar result. Our
      findings showed that EDR can be used as a surrogate of original respiration in QT
      RR model for the better understanding of cardiac regulations in young healthy
      subjects. 

PMID- 24110102
TI  - Spatial correlation based artifact detection for automatic seizure detection in
      EEG.
AB  - Automatic EEG-processing systems such as seizure detection systems are more and
      more in use to cope with the large amount of data that arises from long-term EEG
      monitorings. Since artifacts occur very often during the recordings and disturb
      the EEG-processing, it is crucial for these systems to have a good automatic
      artifact detection. We present a novel, computationally inexpensive automatic
      artifact detection system that uses the spatial distribution of the EEG-signal
      and the location of the electrodes to detect artifacts on electrodes. The
      algorithm was evaluated by including it into the automatic seizure detection
      system EpiScan and applying it to a very large amount of data including a large
      variety of EEGs and artifacts. 

PMID- 24110103
TI  - Automatic optimization of parameters for seizure detection systems.
AB  - A parameter optimization method for an automatic seizure detection algorithm
      using the Nelder Mead algorithm is presented. A suitable cost function for joint
      optimization of sensitivity and false alarm rate is proposed. The optimization is
      done using EEG datasets from 23 patients and validated on datasets from another
      23 patients. The resulting sensitivity was 82.3% with a false alarm rate of 0.24
      FA/h. This is a reduction of the false alarm rate by 1.58 FA/h with an acceptable
      loss of sensitivity of 4.3%. 

PMID- 24110104
TI  - Analyzing EEG signals under insulin-induced hypoglycemia in type 1 diabetes
      patients.
AB  - Hypoglycemia is dangerous and considered as a limiting factor of the glycemic
      control therapy for patients with type 1 diabetes mellitus (T1DM). Nocturnal
      hypoglycemia is especially feared because early warning symptoms are unclear
      during sleep so an episode of hypoglycemia may lead to a fatal effect on
      patients. The main objective of this paper is to explore the correlation between
      hypoglycemia and electroencephalography (EEG) signals. To do this, the EEG of
      five T1DM adolescents from an overnight insulin-induced study is analyzed by
      spectral analysis to extract four different parameters. We aim to explore the
      response of these parameters during the clamp study which includes three main
      phases of normal, hypoglycemia and recovery. We also look at data at the blood
      glucose level (BGL) of 3.3-3.9 mmol/l to find a threshold to distinguish between
      non-hypoglycemia and hypoglycemia states. The results show that extracted EEG
      parameters are highly correlated with patients' conditions during the study. It
      is also shown that at the BGL of 3.3 mmol/l, responses to hypoglycemia in EEG
      signals start to significantly occur. 

PMID- 24110105
TI  - Corticospinal signals recorded with MEAs can predict the volitional forearm
      forces in rats.
AB  - We set out to investigate if volitional components in the descending tracts of
      the spinal cord white matter can be accessed with multi-electrode array (MEA)
      recording technique. Rats were trained to press a lever connected to a haptic
      device with force feedback to receive sugar pellets. A flexible-substrate multi
      electrode array was chronically implanted into the dorsal column of the cervical
      spinal cord. Field potentials and multi-unit activities were recorded from the
      descending axons of the corticospinal tract while the rat performed a lever
      pressing task. Forelimb forces, recorded with the sensor attached to the lever,
      were reconstructed using the hand position data and the neural signals through
      multiple trials over three weeks. The regression coefficients found from the
      trial set were cross-validated on the other trials recorded on same day.
      Approximately 30 trials of at least 2 seconds were required for accurate model
      estimation. The maximum correlation coefficient between the actual and predicted
      force was 0.7 in the test set. Positional information and its interaction with
      neural signals improved the correlation coefficient by 0.1 to 0.15. These results
      suggest that the volitional information contained in the corticospinal tract can
      be extracted with multi-channel neural recordings made with parenchymal
      electrodes. 

PMID- 24110106
TI  - The impact of rTMS over the dorsolateral prefrontal cortex on cognitive
      processing.
AB  - The purpose of the present study was to use event-related potentials (ERP) to
      clarify the effect of magnetic stimulation on cognitive processing. A figure
      eight-shaped flat repetitive transcranial magnetic stimulation (rTMS) coil was
      used to stimulate either the region over the left or the right dorsolateral
      prefrontal cortex, which is considered to be the origin of the P300 component.
      Stimulus frequencies were 1.00, 0.75 and 0.50 Hz rTMS. The strength of the
      magnetic stimulation was set at 80% of the motor threshold for each participant.
      The auditory oddball task was used to elicit P300s before and shortly after rTMS,
      and comprised a sequence of sounds containing standard (1 kHz pure tone, 80% of
      trials) and deviant (2 kHz pure tone, 20% of trials) stimuli. We found that a
      1.00 Hz rTMS pulse train over the left dorsolateral prefrontal cortex increased
      P300 latencies by 8.50 ms at Fz, 12.85 ms at Cz, and 11.25 ms at Pz. In contrast,
      neither 0.75 and 0.50 Hz rTMS pulse trains over the left dorsolateral prefrontal
      cortex nor 1.00, 0.75 and 0.50 Hz rTMS pulse trains over the right dorsolateral
      prefrontal cortex altered P300 latencies. These results indicate that rTMS
      frequency affects cognitive processing. Thus, we suggest that the effects of rTMS
      vary according to the activity of excitatory and inhibitory neurons in the
      cerebral cortex. 

PMID- 24110107
TI  - Estimation of templates and timings of spikes in extracellular voltage signals
      containing overlaps of the arbitrary number of spikes.
AB  - Development of methods to detect and classify neural spikes in extracellular
      voltage signals (e.g. commonly referred to as spike sorting) have been one of
      important subjects in neuroscience and neural engineering. Most of previous spike
      sorting methods suffer from unresolved overlaps of spike waveforms which make
      timings and shapes of spikes unclear. Some methods have got a handle on this
      problem, but they had restrictions about the type of electrodes or complexity of
      overlaps. In this paper, we attempted to develop a spike sorting method for the
      signal containing overlaps of the arbitrary number of spikes recorded with
      arbitrary electrodes. We estimated templates and timings of spikes by the
      inference based on hidden Markov model. In order to avoid the problem of too high
      computational cost and too much decomposition caused by assuming arbitrary
      overlaps, we imposed the weak probabilistic penalty on overlaps in the model and
      reduced computation of estimation by approximating low probabilities to zero. As
      the result of assessments using simulated signal and real extracellular
      recordings, we showed that proposed method could robustly detect and sort
      complexly overlapped spikes. 

PMID- 24110108
TI  - Effects of daytime exposures to short- and middle-wavelength lights on cortical
      activity during a cognitive task.
AB  - This study aimed to assess the effects of light wavelength on human cortical
      activity during a cognitive task, by observing event-related potentials (ERPs).
      We measured ERPs when subjects perform an auditory oddball task under daytime
      exposures to short- and middle-wavelength lights. In the oddball task, a standard
      tone of 1 kHz and a target tone of 2 kHz were used. Subjects were instructed to
      press a button as soon as they heard the target tone. The ERP component that
      occurs approximately 300 ms after a stimulus onset (P300) was analyzed. The
      results showed that amplitude of P300 in the short-wavelength light condition was
      significantly larger than that in the middle-wavelength light condition
      approximately 10-20 min after the start of light exposure. It has been suggested
      that the amplitude of P300 reflects the amount of attentional resources for a
      given task. Therefore, the results obtained suggest that amount of attentional
      resource allocated to the oddball task is increased during exposure to the short
      wavelength light in the daytime. 

PMID- 24110109
TI  - Transient acceleration response of a bone-conducted ultrasonic pulse in living
      human head.
AB  - Ultrasonic hearing through bone-conduction is referred to as bone-conducted
      ultrasound (BCU). Because the perceptual mechanisms of ultrasonic hearing are
      still unclear, it is necessary to approach the subject from various aspects to
      clarify such mechanisms; the propagation process of ultrasonic vibration in the
      head is one of them. To estimate propagation pathways and modes of BCU in living
      human head, we measured the transient acceleration responses for ultrasonic
      pulses. The acceleration responses were obtained at the left and right ears
      simultaneously for left-side, right-side and forehead excitations. Transient
      responses show that there are several transmission pathways or modes, and the
      dominant pathways of BCU were identified. 

PMID- 24110110
TI  - QRS classification and spatial combination for robust heart rate detection in low
      quality fetal ECG recordings.
AB  - Non-invasive fetal electrocardiography (ECG) can be used for prolonged monitoring
      of the fetal heart rate (FHR). However, the signal-to-noise-ratio (SNR) of non
      invasive ECG recordings is often insufficient for reliable detection of the FHR.
      To overcome this problem, source separation techniques can be used to enhance the
      fetal ECG. This study uses a physiology-based source separation (PBSS) technique
      that has already been demonstrated to outperform widely used blind source
      separation techniques. Despite the relatively good performance of PBSS in
      enhancing the fetal ECG, PBSS is still susceptible to artifacts. In this study an
      augmented PBSS technique is developed to reduce the influence of artifacts. The
      performance of the developed method is compared to PBSS on multi-channel non
      invasive fetal ECG recordings. Based on this comparison, the developed method is
      shown to outperform PBSS for the enhancement of the fetal ECG. 

PMID- 24110111
TI  - A 1V low power second-order delta-sigma modulator for biomedical signal
      application.
AB  - This paper presents the design and implementation of a low-power delta-sigma
      modulator for biomedical application with a standard 90 nm CMOS technology. The
      delta-sigma architecture is implemented as 2nd order feedforward architecture. A
      low quiescent current operational transconductance amplifier (OTA) is utilized to
      reduce power consumption. This delta-sigma modulator operated in 1V power supply,
      and achieved 64.87 dB signal to noise distortion ratio (SNDR) at 10 KHz bandwidth
      with an oversampling ratio (OSR) of 64. The power consumption is 17.14 uW, and
      the figure-of-merit (FOM) is 0.60 pJ/conv.

PMID- 24110112
TI  - An ADC-free adaptive interface circuit of resistive sensor for electronic nose
      system.
AB  - The initial resistance of chemiresistive gas sensors could be affected by
      temperature, humidity, and background odors. In a sensing system, the traditional
      interface circuit always requires an ADC to convert analog signal to digital
      signal. In this paper, we propose an ADC-free adaptive interface circuit for a
      resistive gas sensor to read sensor signal and cancel the baseline drift.
      Furthermore, methanol was used to test the proposed interface circuit, which was
      connected with a FIGARO(r) gas sensor. This circuit was fabricated by TSMC 0.18
      um CMOS process, and consumed 86.41 uW under 1 V supply voltage.

PMID- 24110113
TI  - Extraction of intended palpation times from facial EMGs in a mouse model of
      active sensing.
AB  - The rodent whisker system is a common model for somatosensory neuroscience and
      sensorimotor integration. In support of ongoing efforts to assess neural
      stimulation approaches for future sensory prostheses, in which we deliver
      optogenetic stimulation to the somatosensory cortex of behaving mice, we must
      coordinate feedback in real time with active sensing whisker motions. Here we
      describe methods for extracting the times of whisker palpations from bilateral
      bipolar facial electromyograms (EMG). In particular, we show onset times
      extracted offline from EMG envelopes lead whisker motion onsets extracted from
      high speed video (HSV) by ~ 16 ms. While HSV provides ground truth for sensing
      motions, it is not a feasible source of real time information suitable for
      neurofeedback experiments. As an alternative, we find the temporal derivative of
      the EMG envelope reliably predicts whisker motion onsets with short latency. Thus
      EMG, although providing noisy and partial information, can serve well as an input
      to control algorithms for testing neural processing of active sensing
      information, and providing stimulation for artificial touch experiments. 

PMID- 24110116
TI  - Removing cardiac interference from the electroencephalogram using a modified Pan
      Tompkins algorithm and linear regression.
AB  - Cardiac interference can alter the results of quantitative electroencephalograms
      (qEEG) used for medical diagnoses. The methods currently employed for the
      automated removal of cardiac interference, which rely solely on the
      electroencephalogram (EEG), are susceptible to non-cardiac interference commonly
      encountered in EEGs. Methods that rely on the electrocardiogram (ECG)--besides
      being unreliable when non-cardiac artifacts corrupt the ECG--either assume
      periodicity of the cardiac (QRS) peaks or alter uncorrupted EEG segments. This
      paper proposes a robust method for the automated removal of cardiac interference
      from EEGs by identifying QRS peaks in the ECG without assuming periodicity.
      Artificial signals consisting only of QRS peaks and the zero-lines in between are
      computed. Linear regression of the EEG channels on the "QRS signals" removes
      cardiac interference without altering uncorrupted EEG segments. The QRS-based
      regression method was tested on 30 multi-channel EEGs exhibiting cardiac
      interference of elderly subjects (15 male, 15 female). Achieving a correction
      rate of 80%, the QRS-based regression method has proved effective in removing
      cardiac interference from the EEG even in presence of additional non-cardiac
      interference in the EEG.

PMID- 24110115
TI  - Increased variability in respiratory parameters heralds obstructive events in
      children with sleep disordered breathing.
AB  - Sleep disordered breathing (SDB) is characterized by repeated episodes of central
      or obstructive apneas, disturbing respiratory patterns. The purpose of this study
      is to quantify respiratory variability associated with apneic/hypopneic events by
      computing respiratory parameters and thoraco-abdominal asynchrony (TAA) over
      sleep periods preceding the occurrence of obstructive events in children with
      SDB. One minute artifact-free epochs of ribcage (RC) and abdominal (AB) signals
      were extracted from the respiratory inductive plethysmograph (RIP) channel of the
      PSG prior to the onset of each obstruction. Breath-by-breath values of TAA were
      computed using a Hilbert transform based technique that measures the phase shift
      between the RC and AB signals. In addition, the following parameters were
      computed breath-by-breath from the RC signal: inspiratory time (Ti), expiratory
      time (Te), total time (Ttot), and the inspiratory duty cycle (DC=Ti/Ttot).
      Standard deviation of the parameters (SD_TAA, SD_Ti, SD_Te, SD_Ttot, SD_DC) over
      each 1 min epoch were calculated and averaged over each subject with respect to
      sleep stage. For comparison, similar measures were computed from within quiet
      breathing periods of each subject. We found that breaths immediately before
      apnea/hypopneas were associated with a high degree of variability in respiratory
      timing and TAA. The proposed variability analysis of RIP signals may be useful
      for detecting acute epochs of respiratory instability in children with SDB. 

PMID- 24110117
TI  - Preprocessing by means of subspace projections for continuous Cerebral
      Autoregulation assessment using NIRS.
AB  - Cerebral Autoregulation (CA) refers to the capability of the brain to maintain a
      more or less stable cerebral blood flow (CBF), despite the changes in blood
      perfusion. Monitoring this mechanism is of vital importance, especially in
      neonates, in order to prevent damage due to ischemia or hemorrhage. In clinical
      practice near-infrared spectroscopy (NIRS) measurements are used as a surrogate
      measurement for CBF. However, NIRS signals are highly dependent on the variations
      in arterial oxygen saturation (SaO2). Therefore, only segments with relatively
      constant SaO2 are used for CA assessment; which limits the possibilities of the
      use of NIRS for online monitoring. In this paper we propose the use of subspace
      projections to subtract the influence of SaO2 from NIRS measurements. Since this
      approach will be used in an online monitoring system, this preprocessing is
      carried out in a window-by-window framework. However, the use of subspace
      projections in consecutive segments produces discontinuities; we propose a
      methodology to reduce these effects. Obtained results indicate that the proposed
      method reduces the effect of discontinuities between consecutive segments. In
      addition, this methodology is able to subtract the influence of SaO2 from NIRS
      measurements. This approach facilitates the introduction of NIRS for online CA
      assessment. 

PMID- 24110118
TI  - A speech enhancement method for cochlear implant listeners.
AB  - This paper discusses a single-channel speech enhancement method for cochlear
      implant listeners. It is assumed that the Fourier Transform coefficients of
      speech and background noise have different statistical distributions. A
      statistical-model-based method is adopted to update the signal-to-noise ratio and
      estimate the background noise so that the musical noise and speech distortion
      induced by traditional spectral subtraction method can be effectively reduced.
      This enhancement method was evaluated on seven postlingually deaf Chinese
      cochlear implant listeners in comparison with other two speech enhancement
      methods. Test materials were Mandarin sentences corrupted by three different
      types of background noise. Experimental results showed that the proposed speech
      enhancement method could benefit the speech intelligibility of Chinese cochlear
      implant listeners. The results suggest that different noise types may affect the
      performance of different speech enhancement algorithms. 

PMID- 24110120
TI  - OSA severity assessment based on sleep breathing analysis using ambient
      microphone.
AB  - In this paper, an audio-based system for severity estimation of obstructive sleep
      apnea (OSA) is proposed. The system estimates the apnea-hypopnea index (AHI),
      which is the average number of apneic events per hour of sleep. This system is
      based on a Gaussian mixture regression algorithm that was trained and validated
      on full-night audio recordings. Feature selection process using a genetic
      algorithm was applied to select the best features extracted from time and spectra
      domains. A total of 155 subjects, referred to in-laboratory polysomnography (PSG)
      study, were recruited. Using the PSG's AHI score as a gold-standard, the
      performances of the proposed system were evaluated using a Pearson correlation,
      AHI error, and diagnostic agreement methods. Correlation of R=0.89, AHI error of
      7.35 events/hr, and diagnostic agreement of 77.3% were achieved, showing
      encouraging performances and a reliable non-contact alternative method for OSA
      severity estimation. 

PMID- 24110121
TI  - Noninvasive cellular quantity measurement in Bone Marrow Stromal Cells/ Beta
      tricalcium phosphate.
AB  - This paper describes noninvasive cellular quantity measurement in Bone Marrow
      Stromal Cells/ beta-tricalcium phosphate. We attempt to identify cellular
      quantity with an ultrasonic system. The ultrasonic waves are reflected at
      boundaries where there is a difference in acoustic impedances of the materials on
      each side of the boundary. Therefore, we focus on the reflected signal. From the
      obtained ultrasonic data, we extract two features; amplitude and frequency.
      Amplitude is obtained from the raw ultrasonic wave, and frequency is calculated
      from frequency spectrum obtained by applying cross-spectrum method. Therefore, we
      suggest the superiority of frequency to analyze Bone Marrow Stromal Cells. This
      study shows the ability of intervention to produce the desired beneficial effect.

PMID- 24110122
TI  - Noncontact screening system with two microwave radars for the diagnosis of sleep
      apnea-hypopnea syndrome.
AB  - There were two key problems in applying Doppler radar to a diagnosis system for
      sleep apnea-hypopnea syndrome. The first is noise associated with body movements
      and the second is the body positions in bed and the changes of the sleeping
      posture. We focused on the changes of the amplitude of the radar output signal
      corresponding to the changes in the tidal volume, and proposed a method of
      detecting the change of the respiratory amplitude value without the influence of
      body position in bed. In addition, we challenged the detection of the apnea
      hypopnea event confirmed by accompanied rise of heart rates. To increase the
      accuracy of heart rate measurement, we propose a new automatic gain control and a
      real-time radar-output channel selection method based on a spectrum shape
      analysis. A prototype of the system was set up at a sleep disorder center in a
      hospital and field tests were carried out with eight subjects. Despite the
      subjects engaging in frequent body movements while sleeping, the system was quite
      effective in the diagnosis of sleep apnea-hypopnea syndrome (the correlation
      coefficient r = 0.98). 

PMID- 24110124
TI  - Quantification of physiological disparities and task performance in stress and
      control conditions.
AB  - In mental stress studies, cerebral activation and autonomic nervous system are
      important distinctly. This study aims to analyze disparities associated with
      scalp potential, which may have impact on autonomic activation of heart during
      mental stress. Ten healthy subjects participated in this study that performed
      arithmetic tasks in stress and control environment. Task difficulty was
      calculated from their correct responses. During the experiment,
      electroencephalogram (EEG) and electrocardiogram (ECG) signals were recorded
      concurrently. Sympathetic innervation of heart was estimated from heart rate
      (HR), which is extracted from the ECG. The value of theta Fz/alpha Pz was
      measured from EEG scalp potential. The results show a significant surge in the
      value of theta Fz/alpha Pz in stress as compared to baseline (p<0.013) and
      control (p<0.042). The results also present tachycardia while in stress as
      compared to baseline (p<0.05). Task difficulty in stress is also considerably
      higher than control environment (p<0.003). 

PMID- 24110123
TI  - Novel algorithm for real-time onset detection of surface electromyography in step
      tracking wrist movements.
AB  - We present a novel algorithm for real-time detection of the onset of surface
      electromyography signal in step-tracking wrist movements. The method identifies
      abrupt increase of the quasi-tension signal calculated from sEMG resulting from
      the step-by-step recruitment of activated motor units. We assessed the
      performance of our proposed algorithm using both simulated and real sEMG signals,
      and compared with two existing detection methods. Evaluation with simulated sEMG
      showed that the detection accuracy of our method is robust to different signal-to
      noise ratios, and that it outperforms the existing methods in terms of bias when
      the noise is large (low SNR). Evaluation with real sEMG analysis also indicated
      better detection performance compared to existing methods. 

PMID- 24110125
TI  - Analysis of EEG signals regularity in adults during video game play in 2D and 3D.
AB  - Video games have long been part of the entertainment industry. Nonetheless, it is
      not well known how video games can affect us with the advancement of 3D
      technology. The purpose of this study is to investigate the EEG signals
      regularity when playing video games in 2D and 3D modes. A total of 29 healthy
      subjects (24 male, 5 female) with mean age of 21.79 (1.63) years participated.
      Subjects were asked to play a car racing video game in three different modes (2D,
      3D passive and 3D active). In 3D passive mode, subjects needed to wear a passive
      polarized glasses (cinema type) while for 3D active, an active shutter glasses
      was used. Scalp EEG data was recorded during game play using 19-channel EEG
      machine and linked ear was used as reference. After data were pre-processed, the
      signal irregularity for all conditions was computed. Two parameters were used to
      measure signal complexity for time series data: i) Hjorth-Complexity and ii)
      Composite Permutation Entropy Index (CPEI). Based on these two parameters, our
      results showed that the complexity level increased from eyes closed to eyes open
      condition; and further increased in the case of 3D as compared to 2D game play. 

PMID- 24110126
TI  - The factors influence compatibility of pulse-pulse intervals with R-R intervals.
AB  - Cardiac autonomic dysfunction assessed by power spectral analysis of
      electrocardigographic (ECG) R-R intervals (RRI) is a useful method in clinical
      research. The compatibility of pulse-pulse intervals (PPI) acquired by
      photoplethysmography (PPG) with RRI is equivocal. In this study, we would like to
      investigate factors influence the compatibility. We recruited 25 young and health
      subjects divided into two groups: normal subjects (Group1, BMI < 24, n=15) and
      overweight subjects (Group2, BMI >/= 24, n=10). ECG and PPG were measured for 5
      minutes. Used cross-approximate entropy (CAE) and Fast Fourier transform (FFT) to
      obtained compatibility between RRI and PPI. The CAE value in Group1 were
      significantly lower than in Group2 (1.71 +/- 0.12 vs. 1.83 +/- 0.11, P = 0.011).
      A positive linear relationship between CAE value and risk factors of metabolic
      syndrome. No significantly difference between LFP/HFP ratio of RRI (LHRRRI) and
      LFP/HFP ratio of PPI (LHRPPI) in Group1 (1.42 +/- 0.19 vs. 1.38 +/- 0.17, P =
      0.064), LHRRRI significantly higher than LHRPPI in Group2 (2.18 +/- 0.37 vs. 1.93
      +/- 0.30, P = 0.005). It should be careful that using PPI to assess autonomic
      function in the obese subjects or the patients with metabolic syndrome.

PMID- 24110127
TI  - Assessing spontaneous baroreflex in aged with pulse-pulse intervals and pulse
      amplitudes.
AB  - Cardiac autonomic dysfunction is a serious condition in the elder subjects.
      Baroreflex sensitivity (BRS) by measuring pulse intervals and blood pressure has
      been proven as an effective indicator. This paper proposes a novel index by
      substitution blood pressure with amplitudes of pressure pulse. We recruited 61
      subjects divided into two groups: healthy young subjects (Group1, n=33), healthy
      elders (Group2, n=28). The wrist pulse pressures of each subject were measured
      for 5 minutes to obtain pulse-pulse intervals and amplitudes then applied within
      the spontaneous sequence technique to calculate the pulse-pulse interval and
      amplitude ratio (PAR). We verified the reproducibility of PAR and agreement with
      spectral analysis of heart rate variability in group1 participants. We discovered
      significant differences between different groups in PAR (Group1 vs. Group2: 0.90
      +/- 0.42 vs. 0.62 +/- 0.27, P=0.010). In contrast with measurements of BRS, this
      study proposes a simple approach without the necessity of blood pressure
      calibration or professional expertise to conduct measurements, thereby providing
      a convenient method for assessing autonomic function at home.

PMID- 24110128
TI  - T-wave alternans search over 24 hour holter ECG recordings based on singular
      value decomposition.
AB  - This paper proposes an efficient method to search for T-wave alternans (TWA) over
      24 hour Holter ECG recordings. After appropriate pre-processing to remove
      baseline drift and artifact, data are segmented to 2 minute successive time
      intervals. For each beat in the segment, singular value decomposition is applied
      to derive orthogonal characteristic signals. Then two prominent orthogonal
      signals are used for the TWA search. A pair of alternans indices is defined for
      each beat as the orthogonal waveform distance between the target beat and the
      adjacent two beats. When alternans presents, the first index will be larger than
      the second index. The periodogram of the sequence of alternans indices in each
      segment yields a useful alternans measure named Alternans Ratio (AR). To show the
      effectiveness of the measure, the method is applied to 25 control and 24 data
      from patients with various cardio vascular disorders. AR distribution showed
      prominent differences among subject groups. It has been demonstrated that the
      measure AR is not only useful to detect the presence of TWA but the AR
      distribution can be used for the stratification of the TWA risk. 

PMID- 24110129
TI  - Classification of vibratory patterns of the upper airway during sleep.
AB  - Upper airway (UA) narrowing and collapse during sleep results in obstructive
      sleep apnea (OSA). We hypothesize that vibratory patterns of snoring can
      distinguish simple snorers from those with OSA. Samples of breath sounds were
      collected from 7 snorers without OSA and 5 with OSA. Snoring pitch (F0) contours
      were found using the robust algorithm for pitch tracking (RAPT). The OSA snoring
      contours showed fluctuating patterns as compared to the smoother patterns of
      simple snorers. This suggests that snoring reveals the underlying instabilities
      of UA tissue in OSA. Conditional random fields, a statistical sequence
      classifier, gave 75% accuracy in distinguishing the 2 groups. 

PMID- 24110130
TI  - Open architecture software platform for biomedical signal analysis.
AB  - Biomedical signals are very important reporters of the physiological status in
      human body. Therefore, great attention is devoted to the study of analysis
      methods that help extracting the greatest amount of relevant information from
      these signals. There are several free of charge softwares which can process
      biomedical data, but they are usually closed architecture, not allowing addition
      of new functionalities by users. This paper presents a proposal for free open
      architecture software platform for biomedical signal analysis, named JBioS.
      Implemented in Java, the platform offers some basic functionalities to load and
      display signals, and allows the integration of new software components through
      plugins. JBioS facilitates validation of new analysis methods and provides an
      environment for multi-methods analysis. Plugins can be developed for
      preprocessing, analyzing and simulating signals. Some applications have been done
      using this platform, suggesting that, with these features, JBioS presents itself
      as a software with potential applications in both research and clinical area. 

PMID- 24110131
TI  - Feasibility study on a perceived fatigue prediction dependent power control for
      an electrically assisted bicycle.
AB  - Several types of electric motor assists have been developed, as a result, it is
      important to control muscular fatigue on-site in terms of health promotion and
      motor rehabilitation. Predicting the perceived fatigue by several biosignal
      related variables with the multiple regression model and polynomial
      approximation, we try to propose a self control design for the electrically
      assisted bicycle (EAB). We also determine the meaningful muscles during pedaling
      by muscle synergies in relation to the motion maturity. In field experiments,
      prediction of ongoing perceived physical fatigue could have the potential of
      suitable control of EAB. 

PMID- 24110132
TI  - Reduction of EEG artefacts induced by vibration in the MR-environment.
AB  - The EEG acquired simultaneously with functional magnetic resonance imaging (fMRI)
      is distorted by a number of artefacts related to the presence of strong magnetic
      fields. In order to allow for a useful interpretation of the EEG data, it is
      necessary to reduce these artefacts. For the two most prominent artefacts,
      associated with magnetic field gradient switching and the heart beat, reduction
      methods have been developed and applied successfully. Due to their repetitive
      nature, such artefacts can be reduced by subtraction of the respective template
      retrieved by averaging across cycles. In this paper, we investigate additional
      artefacts related to the MR environment and propose a method for the reduction of
      the vibration artefact caused by the cryo-cooler compression pumps system. Data
      were collected from the EEG cap placed on an MR head phantom, in order to
      characterise the MR environment related artefacts. Since the vibration artefact
      was found to be repetitive, a template subtraction method was developed for its
      reduction, and this was then adjusted to meet the specific requirements of
      patient data. The developed methodology successfully reduced the vibration
      artefact by about 90% in five EEG-fMRI datasets collected from two epilepsy
      patients. 

PMID- 24110133
TI  - Automatic ictal HFO detection for determination of initial seizure spread.
AB  - High-frequency oscillations (HFOs) are a reliable indicator for the epileptic
      seizure onset zone (SOZ) in ECoG recordings. We propose a novel method for the
      automatic detection of ictal HFOs in the ripple band (80-250 Hz) based on CFAR
      matched sub-space filtering. This allows to track the early propagation of ictal
      HFOs, revealing initial and follow-up epileptic activity on the electrodes. We
      apply this methodology to two seizures from one patient suffering from focal
      epilepsy. The electrodes identified are in very good accordance with the visual
      HFO analysis by clinicians. Furthermore the electrodes with initial HFO activity
      are correlated well with the SOZ (conventional v-activity).

PMID- 24110134
TI  - Seizure prediction using adaptive neuro-fuzzy inference system.
AB  - In this study, we present a neuro-fuzzy approach of seizure prediction from
      invasive Electroencephalogram (EEG) by applying adaptive neuro-fuzzy inference
      system (ANFIS). Three nonlinear seizure predictive features were extracted from a
      patient's data obtained from the European Epilepsy Database, one of the most
      comprehensive EEG database for epilepsy research. A total of 36 hours of
      recordings including 7 seizures was used for analysis. The nonlinear features
      used in this study were similarity index, phase synchronization, and nonlinear
      interdependence. We designed an ANFIS classifier constructed based on these
      features as input. Fuzzy if-then rules were generated by the ANFIS classifier
      using the complex relationship of feature space provided during training. The
      membership function optimization was conducted based on a hybrid learning
      algorithm. The proposed method achieved highest sensitivity of 80% with false
      prediction rate as low as 0.46 per hour. 

PMID- 24110135
TI  - Stochastic relevance analysis of epileptic EEG signals for channel selection and
      classification.
AB  - Time-frequency decompositions (TFDs) are well known techniques that permit to
      extract useful information or features from EEG signals, being necessary to
      distinguish between irrelevant information and the features effectively
      representing the subjacent physiological phenomena, according to some evaluation
      measure. This work introduces a new method to obtain relevant features extracted
      from time-frequency plane for epileptic EEG signals. Particularly, EEG features
      are extracted by common spectral methods such as short time Fourier transform
      (STFT), wavelets transform and Empirical Mode Decomposition (EMD). Then, each
      method is evaluated by Stochastic Relevance Analysis (SRA) that is further used
      for EEG classification and channel selection. The classification measures are
      carried out based on the performance of the k-NN classifier, while the channels
      selected are validated by visual inspection and topographic scalp map. The study
      uses real and multi-channel EEG data and all the experiments have been supervised
      by an expert neurologist. Results obtained in this paper show that SRA is a good
      alternative for automatic seizure detection and also opens the possibility of
      formulating new criteria to select, classify or analyze abnormal EEG channels. 

PMID- 24110136
TI  - Quantitative evaluation of arousal level based on the analyses of microsaccade
      rates and pupil fluctuations.
AB  - In this study, we proposed an objective estimation of decline of arousal level by
      analyzing microsaccade rate and pupil fluctuation while subjects were
      continuously gazing a fixation target. Previous studies show that the slow eye
      movements (SEMs) could be a candidate for an indicator of decline of arousal.
      However, it is not sufficient to evaluate transition of arousal states since SEMs
      appear just prior to sleep onset. To establish more objective assessment of
      arousal, we examined the effects of the transition of arousal on microsaccade
      rate and pupil fluctuation. The subjects were instructed to indicate by mouse
      clicks when they were aware of having slept. We have analyzed the eye movement
      and pupil fluctuation data in advance of the occurrence of SEMs which were
      detected just before the mouse clicks. In the results, longitudinal pupil
      diameter shrinking and gradual rise of microsaccade rate were observed prior to
      SEMs. These results suggest that the arousal level could be evaluated by
      monitoring eye movements and pupil fluctuations. 

PMID- 24110137
TI  - Evaluation of the effectiveness of muscle assistive device using muscle fatigue
      analysis.
AB  - There have been many kinds of wearable robots or wearable assistive devices to
      reduce the burden of workers in several industries. But there is no quantitative
      and objective method to evaluate the effectiveness of the device. In this study,
      a new method to evaluate the effectiveness of the muscle assistive device is
      suggested. 

PMID- 24110138
TI  - Towards a time-feature independent phonocardiogram segmentation.
AB  - Delimitation and classification of each heart sound is a rather difficult task.
      Elevated heart rates, as found in pediatrics and in some adults as well,
      influence some of the most reliable features used by existing methods.
      Furthermore, in real life scenarios, cardiologists will not have the time to
      acquire the signal's length required by some of the existing algorithms, which
      make us think that different approaches ought to be pursued. This paper presents
      the work on heart sound segmentation using structural and energy based features.
      It is an attempt to not rely on features considered crucial to most existing
      approaches. Yet, it achieves a high sensitivity and specificity comparable to
      some literature. 

PMID- 24110139
TI  - Considerations for integration of a physiological radar monitoring system with
      gold standard clinical sleep monitoring systems.
AB  - A design for a physiological radar monitoring system (PRMS) that can be
      integrated with clinical sleep monitoring systems is presented. The PRMS uses two
      radar systems at 2.45 GHz and 24 GHz to achieve both high sensitivity and high
      resolution. The system can acquire data, perform digital processing and output
      appropriate conventional analog outputs with a latency of 130 ms, which can be
      recorded and displayed by a gold standard sleep monitoring system, along with
      other standard sensor measurements.

PMID- 24110140
TI  - Detection of sleep apnea on a per-second basis using respiratory signals.
AB  - There has been a growing interest in out-of-center sleep testing with portable
      devices for accurate diagnosis of sleep apnea syndrome. This paper presents a new
      algorithm that extracts features based on filtering and statistical dispersion of
      the nasal airflow respiration signal and detects apnea events on a per-second
      basis. The data records were randomly selected from the Sleep Heart Health Study
      (SHHS-2) database to represent 100 control subjects with Apnea-Hypopnea Index
      (AHI) less than 5, and 100 apnea subjects with AHI values from 30 to 75. The
      algorithm was optimized according to the product of sensitivity and positive
      predictive value of apnea events among a training dataset of 50 apnea subjects
      with a constraint on the false positive rate among a training dataset of 50
      control subjects. From testing of the algorithm on separate datasets, the false
      positive rate among 50 control subjects was found to be 1.3 events per hour,
      which corresponds to 100% specificity of classifying apnea subjects. The
      sensitivity and positive predictive value among 50 apnea subjects were found to
      be 83.6% and 72.3%, respectively. Among the identified false positive events in
      the apnea subjects, 64.3% of the events were found to be hypopnea events. Thus,
      incorporation of hypopnea detection would enhance the performance of the apnea
      detection algorithm. 

PMID- 24110141
TI  - Computation and study of the low-frequency oscillation of surface electromyogram
      recorded in biceps during isometric upper limb contraction.
AB  - This study has experimentally studied the low frequency oscillation in surface
      electromyogram (sEMG) during isometric muscle contraction for Biceps brachii
      muscle. The time constant corresponding to this low frequency oscillation was
      computed for sEMG. Experiments were repeated for 25 subjects, and for isometric
      muscle contraction, ranging between 25% and 100 % maximum voluntary contraction
      (MVC), while the subjects were given real-time visual feedback of the force of
      contraction, recorded at 1000 samples/ second. The time constant (Tc)
      corresponding to the variability of sEMG was computed using the Hilbert transform
      and envelope detection. The results show that the time constant, Tc of sEMG
      recorded from the biceps during isometric contraction was the same for all the
      subjects, and for different levels of force of muscle contraction, and was 78 ms
      (+/- 1.1). This suggests that the low frequency oscillation of sEMG of the biceps
      brachii muscles is a fundamental property of that muscle, and corresponds to a
      fundamental phenomenon, which has never been observed earlier. By comparison from
      delays reported in literature, this delay is similar to M2 stretch reflex
      latency, and may be attributed to the neural pathway delay.

PMID- 24110142
TI  - Cuffless blood pressure estimation using only photoplethysmography based on
      cardiovascular parameters.
AB  - This study provides cuffless blood pressure estimation. In general, blood
      pressure changes when the subject's condition changes, and it is important to
      estimate it continuously and noninvasively. In many previous studies, they used
      PTT (Pulse Transmission Time) for estimating. However, PTT needs both
      electrocardiogram and photoplethysmography to be measured. Our method needs only
      a finger type photoplethysmographic sensor for estimating. We use the features
      obtained only from photoplethysmography for estimating, instead of PTT obtained
      from electrocardiogram. The features used are accelerated plethysmography's
      waveform, Heart Rate Variability and the rate of photoplethysmography's drift.
      Blood pressure is modeled as the product of CO (Cardiac Output) and TPR (Total
      Peripheral Resistance) in general. Then, we estimated blood pressure as the
      product of eCO and eTPR estimated by proposed photoplethysmography's features
      with Stepwise multiple regression analysis. Therefore, our proposed method
      provides not only blood pressure, but also CO and TPR. As of result, we estimated
      blood pressure based on eCO and eTPR, and we obtained r = 0.71. Therefore, we
      could obtain the result closer to Finometer in accuracy. 

PMID- 24110143
TI  - Automated estimation of relative fundamental frequency.
AB  - Relative fundamental frequency (RFF), defined as the normalized fundamental
      frequencies of vowels surrounding voiceless consonants, has been shown to have a
      characteristic pattern in healthy voices that differs from those with disordered
      voices (e.g. vocal hyperfunction, Parkinson's disease). However no large-scale
      clinical study has been performed, mainly because the current estimation protocol
      requires trained technicians to manually perform this time-consuming task. In
      this study, we developed a method to automate RFF estimation and tested the
      algorithm on recordings from 12 healthy participants and 12 participants with
      Parkinson's disease. The means and variations of RFFs estimated using the
      automation algorithm were similar to the 'gold standard' estimates developed by
      two trained technicians. The mean squared error for the automated estimates, when
      compared to the 'gold standard' RFF estimates, were similar to those estimated
      manually by an additional trained technician. Future work will focus on improving
      vocal cycle detection and extending the automation to estimate RFF from instances
      in running speech. 

PMID- 24110144
TI  - Detection of EMG-based muscle fatigue during cyclic dynamic contraction using a
      monopolar configuration.
AB  - Measurement of surface EMG signals is usually performed using the bipolar (single
      differential) configuration. However, even if contraction during exercise is
      performed until near-complete exhaustion, the change in the surface EMG
      accompanying the fatigue could be undetectable using the bipolar configuration.
      In order to overcome this disadvantage, this study proposes the measurement of
      surface EMG using the monopolar configuration. Experimental results show that the
      monopolar configuration can detect the change in muscle fatigue with greater
      sensitivity and better stability, as compared to the bipolar configuration. 

PMID- 24110145
TI  - Improvements on EMG-based handwriting recognition with DTW algorithm.
AB  - Previous works have shown that Dynamic Time Warping (DTW) algorithm is a proper
      method of feature extraction for electromyography (EMG)-based handwriting
      recognition. In this paper, several modifications are proposed to improve the
      classification process and enhance recognition accuracy. A two-phase template
      making approach has been introduced to generate templates with more salient
      features, and modified Mahalanobis Distance (mMD) approach is used to replace
      Euclidean Distance (ED) in order to minimize the interclass variance. To validate
      the effectiveness of such modifications, experiments were conducted, in which
      four subjects wrote lowercase letters at a normal speed and four-channel EMG
      signals from forearms were recorded. Results of offline analysis show that the
      improvements increased the average recognition accuracy by 9.20%. 

PMID- 24110146
TI  - Microsaccades generated during car driving.
AB  - Microsaccades together with drift and tremor are fixational eye movements that
      are generated when we try to fixate our gaze on a visual target. Besides their
      function in vision to prevent neural adaptation to unchanging retinal image,
      microsaccades have been studied in neuroscience as an indicator of attentional
      states for the last decade. Most of microsaccade researches have been conducted
      in unnatural laboratory environments, using controlled artificial visual stimuli.
      Thus, little is known about the characteristics of microsaccades in natural
      viewing conditions. Here we attempted to evaluate microsaccades during car
      driving condition in the aim of estimating driver's spatial attention. We
      demonstrate that microsaccades are generated during car driving, and the rate of
      microsaccade generation is modulated by road conditions such as appearance of
      pedestrians or/and other cars. 

PMID- 24110147
TI  - Chaotic phase space differential algorithm for real-time detection of ventricular
      arrhythmias: application in animal model.
AB  - Life-threatening ventricular arrhythmias remain the main cause of death among
      patients with cardiovascular diseases. Efforts have been spent on early detection
      of such fatal cardiac signs. We have previously reported a novel chaotic phase
      space differential (CPSD) algorithm in discriminating VPC, VT, and VF from normal
      sinus rhythm with both good sensitivity and specificity. In this article, we
      apply this algorithm on the rat model of calcium induced ventricular tachycardia.
      Peaked CPSD values can be observed along with the occurrence of ventricular
      tachycardia. In addition, minor ECG changes such as new onset S wave or sinus
      arrhythmia can also be noted on CPSD tracing. We believe that the CPSD algorithm
      not only is capable of detecting lethal ventricular arrhythmias, but also is
      potentially a good tool for long-term monitoring the change of ECG signals. 

PMID- 24110148
TI  - Low-power hardware for neural spike compression in BMIs.
AB  - Within brain-machine interface systems, cortically implanted microelectrode
      arrays and associated hardware have a low-power budget for data sampling,
      processing, and transmission. Recent studies have shown the feasibility of data
      transmission rate reduction using compressed sensing on detected neural spikes.
      They provide power savings while maintaining clustering and classification
      abilities. We propose and analyze here a low-power hardware implementation for
      spike detection and compression. The resulting integrated circuit, designed in
      CMOS 65 nm technology, consumes 2.83 uW and provides 97% of data rate reduction.

PMID- 24110149
TI  - Classification of mental tasks in the prefrontal cortex using fNIRS.
AB  - Functional near infrared spectroscopy (fNIRS) is rapidly gaining interest in both
      the Neuroscience, as well as the Brain-Computer-Interface (BCI) community.
      Despite these efforts, most single-trial analysis of fNIRS data is focused on
      motor-imagery, or mental arithmetics. In this study, we investigate the
      suitability of different mental tasks, namely mental arithmetics, word generation
      and mental rotation for fNIRS based BCIs. We provide the first systematic
      comparison of classification accuracies achieved in a sample study. Data was
      collected from 10 subjects performing these three tasks. 

PMID- 24110150
TI  - A brain-computer interface controlled mail client.
AB  - In this paper, we propose a brain-computer interface (BCI) based mail client.
      This system is controlled by hybrid features extracted from scalp-recorded
      electroencephalographic (EEG). We emulate the computer mouse by the motor imagery
      based mu rhythm and the P300 potential. Furthermore, an adaptive P300 speller is
      included to provide text input function. With this BCI mail client, users can
      receive, read, write mails, as well as attach files in mail writing. The system
      has been tested on 3 subjects. Experimental results show that mail communication
      with this system is feasible. 

PMID- 24110151
TI  - A remote constant current stimulator designed for rat-robot navigation.
AB  - In this paper, a remote stimulator is developed for rat-robot navigation based on
      the technique of Brain-Computer-Interface (BCI). The stimulator can output
      constant current from 0 to 1000 uA, which overcome several shortages of our
      previous constant voltage stimulator. The constant current stimulator consists of
      four major components, including power supply, micro control unit (MCU), constant
      current source and bluetooth transceiver for downloading stimulation commands.
      The stimulator has a weight of about 20 g and size of 32 mm*25 mm*6mm. It has
      five channels of stimulation, which are connected with implanted microelectrodes
      in rat brain. The electrical parameters were characterized on three rats with
      different recovery time after brain surgery. Increasing current stimulations were
      applied on the dorsolateral periaqueductal gray (dlPAG) area to prove the effect
      of current stimulation on rat behavior.

PMID- 24110152
TI  - Encode the "STOP" command by photo-stimulation for precise control of rat-robot.
AB  - Studies on behavior control are important for bio-robots designation. For auto or
      manual navigation of the bio-robots, the accuracy of the command execution is
      especially critical. In this paper, we reported a precise "STOP" command for the
      rat-robots by optical stimulation of the central nervous system (CNS). We labeled
      dorsolateral periaqueductal gray (dlPAG) neurons with light sensitive
      channelrhodopsin-2 (ChR2) and directly probed the optical fiber to reactivate
      these neurons. The rats showed freezing behavior only upon the optical
      stimulation with an appropriate range of laser intensity and stimulation
      frequency. Neuron spikes and local field potential (LFP) were simultaneously
      recorded with optical stimulation by optrodes on free moving rat-robots.
      Together, our findings demonstrated the utility of deep brain optical stimulation
      for the stopping behavior of rat-robot control and indicated a potential
      application of optogenetics for precise control of bio-robots in further work. 

PMID- 24110153
TI  - An approximation approach for rendering visual flickers in SSVEP-based BCI using
      monitor refresh rate.
AB  - Steady-state visual evoked potential (SSVEP)-based brain-computer interfaces
      (BCIs) have potential to realize a direct communication between the human brain
      and the external environment in practical situations. In the conventional
      stimulus presentation approach, which requires a constant period of stimulation,
      the number of frequencies that can be presented on a computer monitor is always
      limited by the refresh rate of a monitor. Although an alternative approach that
      uses a variable on/off frame number to approximate a target flickering stimulus
      has been proposed in our recent study, a direct comparison between SSVEPs
      elicited by the conventional constant period approach and the approximation
      approach is still missing. This study aims to compare the amplitude, signal-to
      noise ratio (SNR) and target identification accuracy of SSVEPs elicited using
      these two approaches with a monitor at two refresh rates (75Hz and 120Hz).
      Results of this study suggest that the SSVEPs elicited by the approximation
      approach are mostly comparable with those elicited by the constant period
      approach. 

PMID- 24110154
TI  - Automatic design for independent component analysis based brain-computer
      interfacing.
AB  - This study proposes a new framework, independent component ensemble, to leverage
      the acquired knowledge into a truly automatic and on-line EEG-based brain
      computer interfacing (BCI). The envisioned design includes: (1) independent
      source recover using independent component analysis (ICA) (2) automatic selection
      of the independent components of interest (ICi) associated with human behaviors;
      (3) multiple classifiers with a parallel constructing and processing structure;
      and (4) a simple fusion scheme to combine the decisions from multiple
      classifiers. Its implications in BCI are demonstrated through a sample
      application: cognitive-state monitoring of participants performing a realistic
      sustained-attention driving task. Empirical results showed the proposed ensemble
      design could provide an improvement of 7% ~ 15% in overall accuracy for the
      classification of the arousal state and the driving performance. In summary,
      constructing ICi-ensemble classifiers and combining their outputs demonstrates a
      practical option for ICA-based BCIs to reduce the risk of not obtaining any
      desired independent source or selecting an inadequate component. Most
      importantly, the ensemble design for integrating information across multiple
      brain areas creates potentials for developing more complicated BCIs for real
      world applications.

PMID- 24110155
TI  - Real-time modeling and 3D visualization of source dynamics and connectivity using
      wearable EEG.
AB  - This report summarizes our recent efforts to deliver real-time data extraction,
      preprocessing, artifact rejection, source reconstruction, multivariate dynamical
      system analysis (including spectral Granger causality) and 3D visualization as
      well as classification within the open-source SIFT and BCILAB toolboxes. We
      report the application of such a pipeline to simulated data and real EEG data
      obtained from a novel wearable high-density (64-channel) dry EEG system. 

PMID- 24110156
TI  - Improving session-to-session transfer performance of motor imagery-based BCI
      using Adaptive Extreme Learning Machine.
AB  - Non-stationarity of electroencephalograph (EEG) data from session-to-session
      transfer is one of the challenges for EEG-based brain-computer interface systems,
      which can inversely affect their performance. Among methods proposed to address
      non-stationarity, adaptation is a promising method. In this study, an adaptive
      extreme learning machine (AELM) is proposed to update the initial classifier from
      the calibration session by using chunks of EEG data from the evaluation session
      whereby the common spatial pattern (CSP) algorithm is used to extract the most
      discriminative features. The effectiveness of the proposed algorithm is on motor
      imagery data collected from 12 healthy subjects during a calibration session and
      an evaluation session on a separate day. The results from the proposed AELM were
      compared with non-adaptive ELM and SVM classifiers. The results showed that AELM
      was significantly better (p=0.03). Moreover, the results also showed that
      accumulating the evaluation session data and using them for adapting the
      classifier will significantly improve the performance (p=0.001). Hence, the
      proposed AELM is effective in addressing the non-stationarity of EEG signal for
      online BCI systems.

PMID- 24110158
TI  - Inferring driver's turning direction through detection of error related brain
      activity.
AB  - This work presents EEG-based Brain-computer interface (BCI) that uses error
      related brain activity to improve the prediction of driver's intended turning
      direction. In experiments while subjects drive in a realistic car simulator, we
      show a directional cue before reaching intersection, and analyze error related
      EEG potential to infer if the presented direction coincides with the driver's
      intention. In this protocol, the directional cue provides an initial estimation
      of the driving direction (based on EEG, environmental or previous driving
      habits), and we focus on the recognition of error-potentials it may elicit.
      Experiments with 7 healthy human subjects yield an average classification 0.69 +/
      0.16, which confirms the feasibility of decoding these signals to help
      estimating driver's turning direction. This study can be further exploited by
      intelligent cars to tune their driving assistant systems to improve their
      performance and enhance the driving experience.

PMID- 24110159
TI  - A competitive brain computer interface: multi-person car racing system.
AB  - Brain computer interface (BCI) technique is successfully utilized to bridge the
      interruption between brain and peripheral nerves and muscles, and to establish a
      new pathway making brain directly output information (or command). Up to now, a
      majority of BCI systems are developed to restore communication ability or
      movement functionality for people with severe disabilities, especially for
      paralyzed patients. To our best knowledge, other researchers haven't developed a
      multi-person BCI with competitive mode. Therefore, in this paper, we introduced a
      multi-person car racing system, which allows more than one person to play game at
      the same time and they can compete with each other for the aim of first reaching
      destination. The reason of development of car racing system has two aspects. At
      one hand, we introduced BCI to entertainment industry and provided a prototype
      for entertainment. At the other hand, we proposed a competitive mode for BCI.
      According to practical evaluation, the results demonstrated that our proposed
      system achieved a good performance. 

PMID- 24110160
TI  - Single-trial discrimination of EEG signals for stroke patients: a general multi
      way analysis.
AB  - It has been demonstrated that Brain-Computer Interface (BCI), combined with
      Functional Electrical Stimulation (FES), is an effective and efficient way for
      post-stroke patients to restore motor function. However, traditional feature
      extraction methods, such as Common Spatial Pattern (CSP), do not work well for
      post-stroke patients' EEG data due to its irregular patterns. In this study, we
      introduce a novel tensorbased feature extraction algorithm, which takes both
      spatial-spectral-temporal features of EEG data into consideration. EEG data
      recorded from post-stroke patients is used for simulation experiments to assess
      the effectiveness of the proposed algorithm. The results show that the the
      proposed algorithm outperforms some traditional algorithms. 

PMID- 24110161
TI  - Gaussian mixture modeling in stroke patients' rehabilitation EEG data analysis.
AB  - Traditional 2-class Motor Imagery (MI) Electroencephalography (EEG)
      classification approaches like Common Spatial Pattern (CSP) and Support Vector
      Machine (SVM) usually underperform when processing stroke patients'
      rehabilitation EEG which are flooded with unknown irregular patterns. In this
      paper, the classical CSP-SVM schema is improved and a feature learning method
      based on Gaussian Mixture Model (GMM) is utilized for depicting patients' imagery
      EEG distribution features. We apply the proposed modeling program in two
      different modules of our online BCI-FES rehabilitation platform and achieve a
      relatively higher discrimination accuracy. Sufficient observations and test cases
      on patients' MI data sets have been implemented for validating the GMM model. The
      results also reveal some working mechanisms and recovery appearances of impaired
      cortex during the rehabilitation training period. 

PMID- 24110162
TI  - DTU BCI speller: an SSVEP-based spelling system with dictionary support.
AB  - In this paper, a new brain computer interface (BCI) speller, named DTU BCI
      speller, is introduced. It is based on the steady-state visual evoked potential
      (SSVEP) and features dictionary support. The system focuses on simplicity and
      user friendliness by using a single electrode for the signal acquisition and
      displays stimuli on a liquid crystal display (LCD). Nine healthy subjects
      participated in writing full sentences after a five minutes introduction to the
      system, and obtained an information transfer rate (ITR) of 21.94 +/- 15.63
      bits/min. The average amount of characters written per minute (CPM) is 4.90 +/-
      3.84 with a best case of 8.74 CPM. All subjects reported systematically on
      different user friendliness measures, and the overall results indicated the
      potentials of the DTU BCI Speller system. For subjects with high classification
      accuracies, the introduced dictionary approach greatly reduced the time it took
      to write full sentences. 

PMID- 24110163
TI  - Movement related cortical potentials in severe chronic stroke.
AB  - Movement related cortical potentials (MRCPs) have been studied for many years and
      controlled using brain computer interfaces (BCIs). Furthermore, MRCPs have been
      proposed as reliable and immediate indicators of cortical reorganizations in
      motor learning and after stroke. In this study MRCPs preceding and during hand
      movements in severe chronic stroke were investigated. Eight severely impaired (no
      residual finger extension) chronic stoke patients underwent EEG and EMG
      recordings during a cue triggered hand movement paradigm. Four patients presented
      subcortical lesions only while the other four presented mixed (cortical and
      subcortical) lesions. MRCPs were measured before (slow cortical potentials SCPs)
      and at movement onset (motor potentials MPs). SCPs were observed during paretic
      hand movements only. Latencies were longer and reached their negativity peak
      earlier during paretic hand movement. When dividing the patients in subcortical
      only and mixed lesion patients, we observed significantly bigger MP peak
      amplitudes over the lesioned hemisphere during paretic and healthy hand movements
      in subcortical stroke patients. Furthermore, we observed a significant difference
      in MP peak latency between subcortical and mixed stroke patients during paretic
      hand movements. We demonstrated for the first time significant differences
      between subcortical only and mixed (cortical and subcortical) stroke patients'
      MRCPs during motor preparation and execution. Furthermore, we demonstrated how
      stroke produces a longer MRCP and that lesion location affects MP peak amplitude
      and latency. Finally, we propose the use MRCP based BCIs to reduce their duration
      (towards normal) and induce motor function recovery. 

PMID- 24110164
TI  - Frequency recognition methods for dual-frequency SSVEP based brain-computer
      interface.
AB  - Dual-frequency steady-state visual evoked potential (SSVEP) was suggested to
      generate more stimuli using a few flickering frequencies for brain-computer
      interface. Dual--frequency SSVEP peaks at more than two frequencies-both main and
      harmonic frequencies. However multi-frequency recognition strategy has not been
      investigated for dual-frequency SSVEP. In this paper, three modified power
      spectral density analysis (PSDA) methods and two modified canonical correlation
      analysis (CCA) methods were tested for dual-frequency SSVEP classification. Three
      methods among the five methods used conventional features or classification
      techniques, and the other two methods used modified features for harmonic
      frequencies. As a result, CCA with novel features showed the best BCI
      performance. Also the use of harmonic frequencies improved BCI performance of
      dual-frequency SSVEP.

PMID- 24110165
TI  - Classification of brain signals associated with imagination of hand grasping,
      opening and reaching by means of wavelet-based common spatial pattern and mutual
      information.
AB  - An important issue in designing a practical brain-computer interface (BCI) is the
      selection of mental tasks to be imagined. Different types of mental tasks have
      been used in BCI including left, right, foot, and tongue motor imageries.
      However, the mental tasks are different from the actions to be controlled by the
      BCI. It is desirable to select a mental task to be consistent with the desired
      action to be performed by BCI. In this paper, we investigated the detecting the
      imagination of the hand grasping, hand opening, and hand reaching in one hand
      using electroencephalographic (EEG) signals. The results show that the ERD/ERS
      patterns, associated with the imagination of hand grasping, opening, and reaching
      are different. For classification of brain signals associated with these mental
      tasks and feature extraction, a method based on wavelet packet, regularized
      common spatial pattern (CSP), and mutual information is proposed. The results of
      an offline analysis on five subjects show that the two-class mental tasks can be
      classified with an average accuracy of 77.6% using proposed method. In addition,
      we examine the proposed method on datasets IVa from BCI Competition III and IIa
      from BCI Competition IV. 

PMID- 24110166
TI  - The potential of multilateral analyses of neuronal activities in future brain
      machine interface research.
AB  - Current brain-machine interfaces are based on the implicit assumption that
      information encoded by neuronal activities does not change despite some recent
      physiological studies indicating that information encoded by neuronal activities
      changes. Here, we highlight the necessity for advanced decoding of neuronal
      activities. Especially, we discuss the advantages of multilateral analyses of
      neuronal activities, including synchronization and variability. 

PMID- 24110167
TI  - Toward binary brain computer interface using steady-state visually evoked
      potential under eyes closed condition.
AB  - It is highly difficult for severely amyotrophic lateral sclerosis and heavily
      spinal cord injury patients to use the brain computer interfaces (BCIs) based on
      the steady-state visual evoked potential (SSVEP) which need to control the
      direction of their eye gaze. We investigated amplitude change of the SSVEP
      associated with mental concentration on flicker to develop the SSVEP-based BCI
      usable under eyes-closed condition. Under the stimulus conditions of the
      flickering frequency of 10 Hz and the stimulus intensity of 5 lx, significant
      difference between the SSVEP amplitude in relaxed state and that in concentrated
      state was observed in the wide region of the scalp except the left frontal
      region, while such significance was also seen in the bilateral occipital lobes
      and left parietal region under the conditions of 14 Hz and 5 lx. Such an impact
      of mental concentration on the SSVEP amplitude was reproducible. 

PMID- 24110168
TI  - Development of an "eyes-closed" brain-computer interface system for communication
      of patients with oculomotor impairment.
AB  - The goal of this study was to develop a new steady-state visual evoked potential
      (SSVEP)-based BCI system, which can be applied to disabled individuals with
      impaired oculomotor function. The developed BCI system allows users to express
      their binary intentions without needing to open their eyes. To present visual
      stimuli, we used a pair of glasses with two LEDs flickering at different
      frequencies. EEG spectral patterns were classified in real time while
      participants were attending to one of the presented visual stimuli with their
      eyes closed. Through offline experiments performed with 11 healthy participants,
      we confirmed that SSVEP responses could be modulated by visual selective
      attention to a specific light stimulus penetrating through the eyelids, and could
      be classified with accuracy high enough for use in a practical BCI system. After
      customizing the parameters of the proposed SSVEP-based BCI paradigm based on the
      offline analysis results, binary intentions of five healthy participants and one
      locked-in state patient were classified online. The average ITR of the online
      experiments reached to 10.83 bits/min with an average accuracy of 95.3 %. An
      online experiment applied to a patient with ALS showed a classification accuracy
      of 80 % and an ITR of 2.78 bits/min, demonstrating the practical feasibility of
      our BCI paradigm. 

PMID- 24110169
TI  - Development of a hybrid mental speller combining EEG-based brain-computer
      interface and webcam-based eye-tracking.
AB  - The main goal of this study was to develop a hybrid mental spelling system
      combining a steady-state visual evoked potential (SSVEP)-based brain-computer
      interface (BCI) technology and a webcam-based eye-tracker, which utilizes
      information from the brain electrical activity and eye gaze direction at the same
      time. In the hybrid mental spelling system, a character decoded using SSVEP was
      not typed if the position of the selected character was not matched with the eye
      direction information ('left' or 'right') obtained from the eye-tracker. Thus,
      the users did not need to correct a misspelled character using a 'BACKSPACE' key.
      To verify the feasibility of the developed hybrid mental spelling system, we
      conducted online experiments with ten healthy participants. Each participant was
      asked to type 15 English words consisting of 68 characters. As a result, 16.6
      typing errors could be prevented on average, demonstrating that the implemented
      hybrid mental spelling system could enhance the practicality of our mental
      spelling system. 

PMID- 24110170
TI  - Character identification by maximizing the difference between target and non
      target responses in EEG without sophisticated classifiers.
AB  - We propose a simple character identification method demonstrated by using an
      electroencephalogram (EEG) with a stimulus presentation technique. The method
      assigns a code maximizing the minimum Hamming distance between character codes.
      Character identification is achieved by increasing the difference between target
      and non-target responses without sophisticated classifiers such as neural network
      or support vector machine. Here, we introduce two kinds of scores reflecting the
      existence of the P300 component from the point of time and frequency domains. We
      then applied this method to character identification using a 3 * 3 matrix and
      compared the results to that of a conventional P300 speller. The accuracy of
      character identification with our method indicated a performance of 100%
      character identification from five subjects. In contrast, the correct character
      was detected in two subjects and a wrong one was detected for one subject. For
      the remaining two subjects, no character was detected within ten trials. Our
      method required 4.8 trials on average to detect the correct character.

PMID- 24110171
TI  - High-frequency spectral changes in Dorsolateral Prefrontal Cortex for potential
      neuoroprosthetics.
AB  - Dorsolateral Prefrontal Cortex (DLPFC) has been associated with goal encoding in
      primates. Thus far, the majority of research involving DLPFC, including all
      electrophysiology studies, has been performed in non-human primates. In this
      paper, we explore the possibility of utilizing the cortical activity in DLPFC in
      humans for use in Brain-Computer Interfaces (BCIs). Electrocorticographic signals
      were recorded from seven patients with intractable epilepsy who had electrode
      coverage over DLPFC. These subjects performed a visuomotor target-based task to
      assess DLPFC's involvement in planning, execution, and accomplishment of the
      simple motor task. These findings demonstrate that there is a distinct high
      frequency spectral component in DLPFC associated with accomplishment of the task.
      It is envisioned that these signals could potentially provide a novel
      verification of task accomplishment for a BCI. 

PMID- 24110172
TI  - An efficient words typing P300-BCI system using a modified T9 interface and
      random forest classifier.
AB  - The conventional P300-based character spelling BCI system consists of a character
      presentation paradigm and a classification system. In this paper, we propose
      modifications to both in order to increase the word typing speed and accuracy. In
      the paradigm part, we have modified the T9 (Text on Nine keys) interface which is
      similar to the keypad of mobile phones being used for text messaging. Then we
      have integrated a custom-built dictionary to give word suggestions to a user
      while typing. The user can select one out of the given suggestions to complete
      word typing. Our proposed paradigms significantly reduce the word typing time and
      make words typing more convenient by typing complete words with only few initial
      character spellings. In the classification part we have adopted a Random Forest
      (RF) classifier. The RF improves classification accuracy by combining multiple
      decision trees. We conducted experiments with five subjects using the proposed
      BCI system. Our results demonstrate that our system increases typing speed
      significantly: our proposed system took an average time of 1.83 minutes per word,
      while typing ten random words, whereas the conventional spelling required 3.35
      minutes for the same words under the same conditions, decreasing the typing time
      by 45.37%. 

PMID- 24110173
TI  - Common spatial patterns for steady-state somatosensory evoked potentials.
AB  - Steady-state somatosensory evoked potential (SSSEP) is a recently developing
      brain-computer interface (BCI) paradigm where the brain response to tactile
      stimulation of a specific frequency is used. Thus far, spatial information was
      not examined in depth in SSSEP BCI, because frequency information was regarded as
      the main concern of SSSEP analysis. However, given that the somatosensory cortex
      areas, each of which correspond to a different body part, are well clustered, we
      can assume that the spatial information could be beneficial for SSSEP analysis.
      Based on this assumption, we apply the common spatial pattern (CSP) method, which
      is the spatial feature extraction method most widely used for the motor imagery
      BCI paradigm, to SSSEP BCI. Experimental results show that our approach, where
      two CSP methods are applied to the signal of each frequency band, has a
      performance improvement from 70% to 75%. 

PMID- 24110174
TI  - Performance of a tactile P300 speller for healthy people and severely disabled
      patients.
AB  - P300 based Brain-Computer Interfaces (BCIs) for communication are well known
      since many years. Most of them use visual stimuli to elicit evoked potentials
      because it is easy to integrate a high number of different classes into the
      paradigm. Nevertheless, a BCI that depends on visual stimuli is sometimes not
      feasible due to the presence of visual impairment in patients with severe brain
      injuries. In this case, it could be possible to use auditory or somatosensory
      stimulation. In this publication a vibrotactile P300 based BCI is introduced. Two
      different approaches were tested: a first approach using two stimulators and a
      second one that utilizes three stimulators for emitting the stimuli. The two
      paradigms were tested on 16 users: A group of ten healthy users and a second
      group comprising of 6 patients suffering Locked-In Syndrome. The control accuracy
      was calculated for both groups and both approaches, proving the feasibility of
      the device, not only for healthy people but also in severely disabled patients.
      In a second step we evaluated the influence of the number of stimuli on the
      accuracy. It was shown that in many cases the maximum accuracy was already
      reached with a small number of stimuli, this could be used in future tests to
      speed up the Information transfer rate. 

PMID- 24110175
TI  - Detection of the optimal region of interest for camera oximetry.
AB  - The estimation of heart rate and blood oxygen saturation with an imaging array on
      a mobile phone (camera oximetry) has great potential for mobile health
      applications as no additional hardware other than a camera and LED flash enabled
      phone are required. However, this approach is challenging as the configuration of
      the camera can negatively influence the estimation quality. Further, the number
      of photons recorded with the photo detector is largely dependent on the optical
      path length, resulting in a non-homogeneous image. In this paper we describe a
      novel method to automatically detect the optimal region of interest (ROI) for the
      captured image to extract a pulse waveform. We also present a study to select the
      optimal camera settings, notably the white balance. The experiments show that the
      incandescent white balance mode is the preferable setting for camera oximetry
      applications on the tested mobile phone (Samsung Galaxy Ace). Also, the ROI
      algorithm successfully identifies the frame regions which provide waveforms with
      the largest amplitudes. 

PMID- 24110176
TI  - Design and tests of a smartphones-based multi-lead ECG monitoring system.
AB  - With the rapid development of wireless communications and sensor technologies,
      multi-lead electrocardiogram (ECG) monitoring systems can be implemented for real
      time Cardiovascular Disease (CVD) tracking and prevention services by using
      mobile terminals. To meet this objective, we designed a 7-lead ECG monitoring
      system enabled by smartphones, which is a combination of user mobility
      requirement and clinical intelligent function. In the system, an application
      layer protocol is conceived and tested for guaranteeing data transmission
      reliability between smartphones and portable sensors. In addition, the smartphone
      in the system can be customized as a personal health manager, which can control
      system function modes and device states, and also perform information management
      and deeper data analysis. Most significantly, we developed a health risk alarm
      algorithm to detect ECG signal abnormities, which could help professionals pick
      out the data with key clinical information. To test our system performance and
      validity, we carried out simulation tests and system experiments. The results
      show our system is helpful in CVD prevention services. 

PMID- 24110177
TI  - Improving quality of experience in m-health monitoring system.
AB  - Quality of Experience (QoE) is proposed to evaluate user's overall satisfaction
      with the network system and services. For m-health systems, improving QoE means
      starting from user's view to make patients and doctors (the main users of m
      health system who are especially captious to services related to health) to
      achieve best satisfaction. In this paper, we proposed an improved model for QoE
      of m-health systems based on energy consumption and information integrity
      received by the users, and then explore on how the users' satisfaction with m
      health systems' energy consumption and received information integrity by
      exponential formula, which is influenced by the quantity of the transmitted
      information. Finally, from the results of simulation, we concluded that the
      appropriate compression of information quantity is the best way to improve QoE
      performance of the m-health system. 

PMID- 24110178
TI  - Improving chronic disease management with mobile health platform.
AB  - In modern society, aging and chronic disease is becoming common phenomenon due to
      the increasing numbers of elderly patients. To best treat this growing segment of
      the population, medical care should be based on constant vital sign monitoring.
      In this study, we propose a mobile vital sign measurement and data collection
      system for chronic disease management.. And we implemented a middle ware using
      Multi-Agent platform in SOS (Self-Organizing System) platform that transmits
      patient clinical data for services. We also implemented a HL7 messaging interface
      for interoperability of clinical data exchange. We propose health services on a
      self-organized software platform.

PMID- 24110179
TI  - iACT--an interactive mHealth monitoring system to enhance psychotherapy for
      adolescents with sickle cell disease.
AB  - Sickle cell disease (SCD) is the most common inherited disease, and SCD symptoms
      impact functioning and well-being. For example, adolescents with SCD have a
      higher tendency of psychological problems than the general population. Acceptance
      and Commitment Therapy (ACT), a cognitive-behavioral therapy, is an effective
      intervention to promote quality of life and functioning in adolescents with
      chronic illness. However, traditional visit-based therapy sessions are restrained
      by challenges, such as limited follow-up, insufficient data collection, low
      treatment adherence, and delayed intervention. In this paper, we present Instant
      Acceptance and Commitment Therapy (iACT), a system designed to enhance the
      quality of pediatric ACT. iACT utilizes text messaging technology, which is the
      most popular cell phone activity among adolescents, to conduct real-time
      psychotherapy interventions. The system is built on cloud computing technologies,
      which provides a convenient and cost-effective monitoring environment. To
      evaluate iACT, a trial with 60 adolescents with SCD is being conducted in
      conjunction with the Georgia Institute of Technology, Children's Healthcare of
      Atlanta, and Georgia State University. 

PMID- 24110180
TI  - Design of real-time encryption module for secure data protection of wearable
      healthcare devices.
AB  - Wearable devices for biomedical instrumentation could generate the medical data
      and transmit to a repository on cloud service through wireless networks. In this
      process, the private medical data will be disclosed by man in the middle attack.
      Thus, the archived data for healthcare services would be protected by non
      standardized security policy by healthcare service provider (HSP) because HIPAA
      only defines the security rules. In this paper, we adopted the Advanced
      Encryption Standard (AES) for security framework on wearable devices, so
      healthcare applications using this framework could support the confidentiality
      easily. The framework developed as dynamic loadable module targeted for
      lightweight microcontroller such as msp430 within embedded operating system. The
      performance was shown that the module can support the real-time encryption using
      electrocardiogram and photoplethysmogram. In this regard, the processing load for
      enabling security is distributed to wearable devices, and the customized data
      protection method could be composed by HSP for a trusted healthcare service. 

PMID- 24110181
TI  - Local pulse wave velocity estimation using magnetic plethysmograph.
AB  - Pulse Wave Velocity(PWV) is an established measure of arterial stiffness. We
      present a method of measuring local pulse wave velocity by the use of Magnetic
      Plethysmograph(MPG) sensors. The design of a Compact Single element MPG (CS-MPG)
      sensor is presented. The functionality of the sensor is verified by phantom
      experiments. The utility of this sensor for in-vivo measurements of PWV is also
      demonstrated. Further, a Dual-element MPG (D-MPG) for evaluation of local PWV is
      also presented. The error in measurement of PWV using this sensor is
      characterised experimentally and shown to be within acceptable limits. The
      ability of this dual element sensor to measure local PWV in-vivo is also
      demonstrated by trials on volunteers. 

PMID- 24110182
TI  - Detection of hemodynamic adaptations during impending syncope: implementation of
      a robust algorithm based on pulse arrival time measurements only.
AB  - Syncopes are a major public health concern since they can cause severe injuries
      e.g. by associated falls. We previously demonstrated the feasibility of syncope
      prediction based on the pulse arrival time (PAT) analysis. Importantly,
      algorithms for early detection of impending syncope need to be robust against
      measurement noise, in particular photoplethysmography (PPG) artifacts, causing
      false detection. We introduce in this work an algorithm concept to deal with
      artifacts as well as to detect the onset of syncope based on tracking of relative
      PAT changes only. Our method has been shown useful to improve detection
      performance for measurements during impending syncope in patients undergoing head
      up tilt table testing which might improve syncope prediction. 

PMID- 24110183
TI  - A new movement artifact detector for photoplethysmographic signals.
AB  - Oximeters are commonly used in abbreviated cardiorespiratory studies (ACS) to
      monitor blood oxygen saturation and heart rate using the photoplethysmography
      (PPG) signal. These data are prone to movement artifacts, especially in infants
      who move or need to be handled often. Therefore segments of PPG data contaminated
      by movement artifact must be detected as a first stage of analysis. In ACS this
      identification is generally done manually, by having an expert visually assess
      the quality of the signal. This is subjective and very time consuming, especially
      for long data records. For this reason we present a novel detector of PPG
      movement artifacts that uses moving average filters to remove trends, reduce the
      effect of white noise, and notch filter pulse-related information. The normalized
      root mean square of the filtered signal is then used as a detection statistic. We
      demonstrate its detection properties using a data set from infants recovering
      from anesthesia, and show that it performs better than other automated methods
      based on entropy or higher-order statistics. Furthermore, the new method is more
      robust than the other methods in the presence of large noise. 

PMID- 24110184
TI  - The effect of local cold and warm exposure on index finger photoplethysmographic
      signal waveform.
AB  - The study was carried out in order to analyse the changes in
      photoplethysmographic (PPG) signal waveform, which are caused by cold and warm
      stimulation. The study was carried out on 7 subjects. The right hand was immersed
      in cold and warm water up to the wrist during the experiment. The PPG signal was
      registered from right hand index finger. As a reference, the temperatures of
      index finger and pulse transit time (PTT) values were measured. A correlation of
      r = -0.70 was found between normalised slope of the PPG signal and the subject's
      age. The normalised slope increased noticeably due to the cold and decreased due
      to the warm water stimulation. It was opposite to the expected results with PTTs
      and the behaviour has to be investigated in future studies.

PMID- 24110185
TI  - Potential value of electrocardiogram and photoplethysmogram for non-invasive
      blood pressure estimation during exercise.
AB  - Blood pressure (BP) monitoring is required to ensure safety of home-based
      exercise in seniors. Pulse transit time (PTT) defined as the time it takes a
      pulse wave to travel between two arterial sites is considered to be inversely
      proportional to BP. Different approaches have been described to calculate PTT
      using photoplethysmogram (PPG) and electrocardiogram (ECG) however it is not
      clear which approach produces better BP estimates. The purpose of this study was
      to compare potential value of different approaches for calculating PTT and other
      derivatives of PPG and ECG described in the literature for assessing BP during
      exercise. Three calibration points were collected from five study participants at
      different levels of exertion on three different days. A high precision automated
      BP monitor was used to obtain reference BP. A correlation matrix between PPG/ECG
      derivatives and the reference BP values was analyzed. Based on the bivariate
      correlation analysis, PPG/ECG derivatives that demonstrated the most prominent
      association with reference BP were identified. The results of the study confirmed
      the value of individualized calibration for BP estimation using PTT and
      identified optimal means to derive it from PPG and ECG. 

PMID- 24110186
TI  - Estimation of cardiac output and total peripheral resistance in preterm infants
      by arterial waveform analysis.
AB  - This study investigated whether arterial blood pressure waveform analysis could
      be useful for estimating left ventricular outflow (LVO) and total peripheral
      resistance (TPR) in preterm infants. A cohort of 27 infants were studied, with 89
      measurements of left ventricular outflow (LVO) using Doppler echocardiography and
      arterial pressure using catheters, performed in 0, 12, 24 and 36 hours after
      birth. TPR was computed as mean arterial pressure divided by LVO. The diastolic
      decay rate (1/tau) was obtained via fitting an exponential function to the last
      one third of each arterial pulse, with the mean rate computed from 50 pulses
      selected from each infant. This decay rate was considered to be inversely related
      to TPR while positively related to LVO. The results of regression analysis have
      confirmed that the diastolic decay rate had significant positive and negative
      relationships with LVO and TPR respectively(r = 0.383, P = 0.0002 and r = -0.379,
      P = 0.0002 respectively). These preliminary results demonstrated the potential
      utility of arterial pressure waveform analysis for estimating LVO and TPR in
      preterm infants, but more advanced multi-parameter models may be needed to
      improve accuracy of the estimation. 

PMID- 24110187
TI  - Robust separation of visceral and subcutaneous adipose tissues in micro-CT of
      mice.
AB  - One of the common practices in obesity and diabetes studies is to measure the
      volumes and weights of various adipose tissues, among which, visceral adipose
      tissue (VAT) and subcutaneous adipose tissue (SAT) play critical yet different
      physiological roles in mouse aging. In this paper, a robust two-stage VAT/SAT
      separation framework for micro-CT mouse data is proposed. The first stage is to
      distinguish adipose from other tissue types, including background, soft tissue
      and bone, through a robust mixture of Gaussian model. Spatial recognition
      relevant to anatomical locations is carried out in the second step to determine
      whether the adipose is visceral or subcutaneous. We tackle this problem through a
      novel approach that relies on evolving the abdominal muscular wall to keep
      VAT/SAT separated. The VAT region of interest (ROI) is also automatically set up
      through an atlas based skeleton matching procedure. The results of our method are
      compared with VAT/SAT delineations by human experts, and a high classification
      accuracy is demonstrated on eight micro-CT mouse volume sets.

PMID- 24110188
TI  - Virtual colon flattening based on colonic outer surface.
AB  - Virtual colon flattening (VF) is a non-invasive procedure to inspect the colonic
      inner surface for detecting colorectal polyps. Unfortunately, the performance of
      VF is impeded by deformation distortions of colonic inner surface.
      Conventionally, the colonic inner surface itself is used to correct deformation
      distortions. In this paper, we propose a colonic outer surface based VF method to
      correct distortions instead of colonic inner surface. The proposed method was
      validated with 60 cases and 200 annotated polyps. Visual inspections were carried
      out by three operators independently and were compared with three existing VF
      methods which are based on colonic inner surface. The correct detection rate of
      the proposed method and the three existing methods were 88.0%, 76.5%, 80.0% and
      81.5% respectively. False positives per case were 0.16, 0.32, 0.21, and 0.26
      respectively. The proposed method has higher correct detection rate and less
      false positives than the other three VF methods, demonstrating the usefulness of
      colonic outer surface as a correction tool for VF results. 

PMID- 24110189
TI  - Fast grating-based X-ray phase-contrast tomosynthesis.
AB  - As an imaging technique with low radiation dose and improved contrast, digital x
      ray tomosynthesis is widely used in clinical diagnoses. Based on the superior
      capability of x-ray phase-contrast imaging (PCI) techniques for imaging low
      density materials, the combination of X-ray tomosynthesis and PCI can potentially
      provide higher efficiency in the detection of soft tissues. The goal of this work
      was to develop a fast imaging method for phase-contrast tomosynthesis, called
      fast grating-based phase-contrast tomosynthesis (GPC-Tomo), which integrates
      tomosynthesis with a grating-based PCI technique. Following the interlaced phase
      stepping (PS) data collection method, which is much faster than conventional PS
      method, we propose a novel image reconstruction method called inner-focusing (IF)
      reconstruction for the fast GPC-Tomo. The proposed IF reconstruction method was
      validated by real experiments and the results suggested its effectiveness in
      achieving a fast GPC-Tomo. 

PMID- 24110190
TI  - Attenuation correction effects on SPECT/CT procedures: phantoms studies.
AB  - Attenuation correction is widely used in SPECT/CT (Single Photon Emission
      Computed Tomography) procedures, especially for imaging of the thorax region.
      Different compensation methods have been developed and introduced into clinical
      practice. Most of them use attenuation maps obtained using transmission scanning
      systems. However, this gives extra dose of radiation to the patient. The purpose
      of this study was to identify when attenuation correction is really important
      during SPECT/CT procedures.For this purpose, we used Jaszczak phantom and phantom
      with three line sources, filled with technetium ((99m)-Tc), with scattering
      materials, like air, water and acrylic, in different detectors configurations. In
      all images acquired were applied analytic and iterative reconstruction
      algorithms; the last one with or without attenuation correction. We analyzed
      parameters such as eccentricity, contrast and spatial resolution in the
      images.The best reconstruction algorithm on average was iterative, for images
      with 128 * 128 and 64 * 64 matrixes. The analytical algorithm was effective only
      to improve eccentricity in 64 * 64 matrix and matrix in contrast 128 * 128 with
      low statistics. Turning to the clinical routine examinations, on average, for 128
      * 128 matrix and low statistics counting, the best algorithm was the iterative,
      without attenuation correction,improving in 150% the three parameters analyzed
      and, for the same matrix size, but with high statistical counting, iterative
      algorithm with attenuation correction was 25% better than that without
      correction. We can conclude that using the iterative algorithm with attenuation
      correction in the water, and its extra dose given, is not justified for the
      procedures of low statistic counting, being relevant only if the intention is to
      prioritize contrast in acquisitions with high statistic counting.

PMID- 24110191
TI  - A new method for the integration of digital dental models and cone-beam computed
      tomography images.
AB  - This study introduces a regional-surface-based registration without markers for
      integration of laser-scanned dental images into maxillofacial cone-beam computed
      tomography (CBCT) images. The method just needs to manually select three similar
      areas without artifact on the digital dental image and CBCT image, and then the
      process is automatically complete the fusion (superimposition) of maxillofacial
      model and the digital dental model. Then the differences such as mean error and
      root-mean-square (RMS) error are automatically computed between the 2 images
      according to the selected surfaces and expressed in a color scale. Experimental
      results show that the mean errors between the 2 models at the integrated model
      range from 0.15 mm to 0.45 mm and the RMS errors range 0.18 mm to 0.49 mm. The
      numbers are similar to the results of previous methods and reach a desirable
      error. Moreover, it is robust feasibility for especially serious artifacts CBT
      images. It is worth mentioning that all measurements of intra-operator
      reproducibility and inter-operator reliability are excellent. 

PMID- 24110192
TI  - Effect of aluminium filtration on dose and image quality in paediatric slot
      scanning radiography.
AB  - This paper examines the effect that a 1.8 mm aluminium filter has on paediatric
      patient dose and image quality for linear slot scanning radiography (LSSR). A
      dynamic dose prediction model for LSSR accurately predicted the dose reduction
      effects of added aluminium filtration. A cadaver imaging study was carried out to
      assess the effects of filtration on image quality. With 1.8 mm added aluminium
      filtration, no visible degradation to image contrast or clarity was found, and in
      some cases the aluminium filtration improved the image quality as judged by
      radiologists. 

PMID- 24110193
TI  - Multifractal analysis of microvasculature in health and disease.
AB  - A growing body of evidence suggests that there is a strong association between
      neurodegenerative diseases such as Alzheimer's Diseases and the abnormality of
      the cerebral vasculature, in particular the microvessels/capillaries that are
      responsible for the exchange of nutrients across the blood-brain barrier [1].
      Many microvessels are described as being kinked or distorted [2], implying that
      they are modified by some destructive process. Imaging devices such as microCT
      can achieve resolutions on the order of several um, allowing imaging the three
      dimensional (3D) microvasculature down to the capillary level. However, the main
      weakness of using microCT for vascular research is considered to be the lack of
      software for 3D quantification of microvasculature and microvascular image
      databases for developing and testing algorithms. In this paper we describe a
      multifractal analysis method for the microvasculature automatically segmented
      from microCT images of the mouse brain. Due to the lack of a benchmark microCT
      image database, the method has been tested using a surrogate database--a publicly
      available retinal vessel database. The results are preliminary indication of the
      multifractal properties of mouse brain vasculature. A potential solution to
      automated classification of healthy and disease brains are discussed.

PMID- 24110194
TI  - Computed microtomography and X-ray fluorescence analysis for comprehensive
      analysis of structural changes in bone.
AB  - This paper presents the results of a comprehensive analysis of structural changes
      in the caudal vertebrae of Turner's thick-toed geckos by computer microtomography
      and X-ray fluorescence analysis. We present algorithms used for the
      reconstruction of tomographic images which allow to work with high noise level
      projections that represent typical conditions dictated by the nature of the
      samples. Reptiles, due to their ruggedness, small size, belonging to the amniote
      and a number of other valuable features, are an attractive model object for long
      orbital experiments on unmanned spacecraft. Issues of possible changes in their
      bone tissue under the influence of spaceflight are the subject of discussions
      between biologists from different laboratories around the world. 

PMID- 24110195
TI  - Pleura detection in chest computed tomography with application for nodule
      detection.
AB  - This paper proposes an efficient algorithm for detecting pleural objects that
      come in contact with a nodule. To reduce complexity, the algorithm recursively
      performed a curve-fitting method on each slice of the volume of interest to
      locate the object between the parietal and visceral pleurae surfaces and measured
      the quality of the fitting curve. When a nodule contacted the surfaces of the
      chest wall or diaphragm, they were automatically separated using the fitting
      curve. The algorithm was performed on 864 slices of 40 nodules. The segmentation
      results were visually inspected by a consensus of attending physicians to search
      for any segmentation errors. The consensus accepted 93.6% of the segmentation
      results. 

PMID- 24110196
TI  - The feasibility study on 3-dimensional fluorescent x-ray computed tomography
      using the pinhole effect for biomedical applications.
AB  - We propose a 3-dimensional fluorescent x-ray computed tomography (CT) pinhole
      collimator, aimed at providing molecular imaging with quantifiable measures and
      sub-millimeter spatial resolution. In this study, we demonstrate the feasibility
      of this concept and investigate imaging properties such as spatial resolution,
      contrast resolution and quantifiable measures, by imaging physical phantoms using
      a preliminary imaging system developed with monochromatic synchrotron x rays
      constructed at the BLNE-7A experimental line at KEK, Japan. 

PMID- 24110197
TI  - Threshold choices of Huber regularization using global- and local-edge-detecting
      operators for X-ray computed tomographic reconstruction.
AB  - Statistical iterative reconstruction (SIR) approaches have shown great potential
      in x-ray computed tomographic (CT) reconstruction in the case of low-dose
      protocol. For yielding high quality image, an edge-preserving regularization
      should be incorporated into the objective function of SIR approaches. A typical
      example is the Huber regularization with an edge-preserving non-quadratic
      potential function which increases less rapidly than the quadratic potential
      function for sufficiently large arguments. However, a major drawback of the Huber
      regularization is the determining the threshold, which precludes its extensive
      applications. In this paper, we investigate both global- and local- edge
      detecting operators for threshold choices of Huber regularization and apply them
      to SIR CT image reconstruction with low-dose scan protocol. Experiments were
      performed on XCAT phantom by using a CT simulator to obtain the low-dose
      projection data. 

PMID- 24110198
TI  - Radiation dose and accuracy analysis of newly developed cone-beam CT for dental
      and maxillofacial imaging.
AB  - Cone-beam computed tomography (CBCT) has become increasingly popular in dental
      and maxillofacial imaging due to its accurate 3D information, minimal radiation
      dose, and low machine cost. In this paper, we have proposed the newly developed
      CBCT scanner, called DentiiScan. Our gantry system consisting of a cone-beam X
      ray source and an amorphous silicon flat panel detector is rotated around a
      patient's head. With the large area detector, only a single rotation is needed to
      reconstruct the field-of-view area from chin to eyes and our reconstructed
      algorithm based on GPU calculation is about 30 times faster than the CPU-based
      algorithm. The radiation dose was measured and compared to other dental and
      medical CT machines. The absorbed radiation dose from our proposed CBCT machine
      is significantly low. In addition, geometric accuracy was analyzed when the test
      object was scanned at the normal position as well as the inclined position. The
      results from three observers repeated for five times confirm that the machine can
      produce reconstructed images with high accuracy. 

PMID- 24110199
TI  - Computer-aided liver surgical planning system using CT volumes.
AB  - In this paper, we presented our newly developed computer-aided liver surgical
      planning system for patient-specific treatments by using the patient's CT
      volumes. The system is composed of three modules, liver segmentation, vessel
      extraction, and visualization & interaction modules. It can prepare a virtual
      environment for patient-specific liver surgical planning and simulations. We also
      developed an original visualization library, which is based on GPU (graphics
      processing unit) computing for real-time interaction and visualization. The
      effectiveness of our system was evaluated by surgeons with liver surgery
      simulations. 

PMID- 24110200
TI  - A new tool for quantifying and characterizing asymmetry in bilaterally paired
      structures.
AB  - This paper introduces a new tool to quantify and characterize asymmetry in
      bilaterally paired structures. This method uses deformable registration to
      produce a dense vector field describing the point correspondences between two
      images of bilaterally paired structures. The deformation vector field properties
      are clustered to detect and describe regions of relevant asymmetry. Three methods
      are provided to analyze the asymmetries: the global asymmetry score uses cluster
      features to quantify overall asymmetry, the local asymmetry score quantifies
      asymmetry in user-defined regions of interest, and the asymmetry similarity
      measure quantifies pairwise similarity of individual asymmetry. The scores and
      image distances generated by this tool are shown to correlate highly with
      asymmetry ratings assigned by an expert. 

PMID- 24110201
TI  - Method for location of puncture point guided by digital mammography image.
AB  - The main purpose of this study was to develop a method that can optimize the
      algorithm for puncture point calculation, and therefore improve the accuracy of X
      ray guided breast biopsy. The proposed method is: first, select two guiding
      points; then, use the guiding points to construct X-ray cone-beams, so the
      joining section of the cone-beams can be used to determine the puncture target
      point. The method was verified by a phantom emulation, in which the calculated
      target-points were all found within the central part of the target lesion, and
      far away from the boarder of the lesion (change the x-ray tube angle by 15
      degrees  would only cause a slight deviation no more than 1.4 mm), the accuracy
      is enough to fulfill the needs of biopsy operation. This study also found out
      that, the shorter the distance between the guiding point and the center of the
      lesion's project, the nearer the calculated biopsy-point will be to the actual
      lesion center. 

PMID- 24110202
TI  - Curvature analysis of femoral shaft in total knee arthroplasty patient and
      control group.
AB  - For some patients with joint illnesses such as rheumarthritis or varus deformity,
      the total knee arthroplasty (TKA) procedures are performed. However, when
      inserting metal cutting guide for the procedures, due to the femoral shaft
      bowing, complications such as the cortex of the femoral shaft damages or
      secondary fractures can be caused. If the central coordinate value of the femoral
      shaft is known, the metal cutting guide could be inserted into the anatomical
      center, so such complications can be prevented. In this study, CT images of
      femoral shafts of 10 individuals in the experiment group who are in need of
      receiving the total knee arthroplasty procedures and those of 10 individuals in
      the control group without illness in the femoral shaft have been utilized to
      locate the 3-dimensional coordinate values. Then, Matlab was utilized to identify
      the central coordinate value in order to obtain a graph reflecting the anatomical
      shapes as well as to acquire the 3-dimensional curvature values by section. As a
      result, the average curvature range of femoral shafts of the experiment group was
      determined to be 631.2 mm whereas the average curvature range of femoral shafts
      of the control group was determined to be 1430.4 mm. The statistical significant
      of the measured results was verified through ANOVA analysis. Based on these
      results, it was verified that the level of curvature of the femoral shaft of the
      experiment group was higher. If the anatomical central points are located and
      analyzed using this methodology, it would be helpful in performing orthopedic
      operations such as the total knee arthroplasty. 

PMID- 24110204
TI  - A quantitative technique for assessing the change in severity over time in
      psoriatic lesions using computer aided image analysis.
AB  - Psoriasis is a chronic skin disease affecting an estimated 125 million people
      worldwide. One of the key problems in the management of this condition is the
      objective measurement of lesion severity over time. Currently, severity is scored
      by clinicians using visual protocols leading to intra and inter observer
      variability that makes measurement of treatment efficacy subjective. In this
      paper, an automatic computer aided image analysis system is proposed that
      quantitatively assess the changes of erythema and scaling severity of psoriatic
      lesions in long-term treatment. The algorithm proposed in this paper works on 2D
      digital images by selecting features that can be used to accurately segment
      erythema and scaling in psoriasis lesions and assess their changes in severity,
      according to the popular psoriasis area and severity index (PASI). The algorithms
      are validated by developing linear models that correlate well with changes in
      severity scores given by dermatologists. To the best of our knowledge, no such
      computer assisted method for psoriasis severity assessment in a long-term
      treatment exists. 

PMID- 24110203
TI  - 3D CT spine data segmentation and analysis of vertebrae bone lesions.
AB  - A method is presented aiming at detecting and classifying bone lesions in 3D CT
      data of human spine, via Bayesian approach utilizing Markov random fields. A
      developed algorithm for necessary segmentation of individual possibly heavily
      distorted vertebrae based on 3D intensity modeling of vertebra types is presented
      as well. 

PMID- 24110205
TI  - Unfolding X-ray spectra using a flat panel detector.
AB  - It is difficult to measure the energy spectrum of X-ray tubes due to the pile up
      effect produced by the high fluence of photons. Using attenuating materials,
      appropriate detector devices and the Monte Carlo method, primary X-ray spectrum
      of these devices can be estimated. In this work, a flat panel detector with a
      PMMA wedge has been used to obtain a dose curve corresponding to certain working
      conditions of a radiodiagnostic X-ray tube. The relation between the dose curve
      recorded by the flat panel and the primary X-ray spectrum is defined by a
      response function. Normally this function can be approximated by a matrix, which
      can be obtained by means of the Monte Carlo method. Knowing the measured dose
      curve and the response matrix, the primary X-ray spectrum can be unfolded.
      However, there are some problems that strongly affect the applicability of this
      method: i.e. technical features of the flat panel and inherent characteristics of
      the involved radiation physics (ill-posed problem). Both aspects are analyzed in
      this work, concluding that the proposed method can be applied with an acceptable
      accuracy for spectra without characteristic lines, for instance, tungsten anode
      in the 50-70 kVp range. 

PMID- 24110207
TI  - In vivo optical investigation of short term skin water contact and moisturizer
      application using NIR spectroscopy.
AB  - Nowadays, a number of noninvasive methods and instruments are available to
      inspect the biophysical properties and effects of various applicants on human
      skin, providing quantitative measurements and more details regarding the
      interactions between skin and various products. Such methods include Near
      Infrared Spectroscopy (NIRS), a technique which over the years, has gained quite
      a reputation in being able to accurately determine moisture levels and water
      contents due to its sensitivity to hydrogen bonding. This paper reports
      preliminary results of an in vivo study carried out on the skin of a small number
      of human participants, investigating the optical response of human skin after
      direct short-term contact with water followed by application of a moisturizer,
      using a highly advanced spectrophotometer in the region of 900-2100 nm, and
      equipped with a reflectance fibre optic probe. Results obtained here certainly
      raise some questions regarding the optical characteristics of different skin
      types and the influence of frequent moisturizer use, as well as the varying
      response between different water bands in the NIR region. Future work will focus
      on gaining more knowledge about these, in order to further improve optical skin
      measurements, and hopefully support the design and development of a portable
      and/or miniaturized optical device that could provide reliable, accurate and fast
      skin hydration readings in real time.

PMID- 24110208
TI  - Nonstructural protein 1 characteristic peak from NS1-saliva mixture with Surface
      Enhanced Raman spectroscopy.
AB  - Surface Enhanced Raman spectroscopy (SERS) is an enhanced technique of Raman
      spectroscopy, which amplifies the intensity of Raman scattering to a practical
      range with adsorption of analyte onto nano-size plasmonic material such as gold,
      silver or copper. This feature of SERS has given it a niche in tracing molecular
      structure, especially useful for marking diseases specific biomarker. NS1 protein
      has been clinically accepted as an alternative biomarker for diseases caused by
      flavivirus. Detection of Nonstructural Protein 1 (NS1) will allow early diagnosis
      of the diseases. Its presence in the blood serum has been reported as early as
      first day of infection. With gold substrate, our work here intends to explore if
      SERS is suitable to detect NS1 from saliva, with saliva becoming the most favored
      alternative to blood as diagnostic fluid due to its advantages in sample
      collection. Our experimental results find both gold coated slide (GS) and saliva
      being Raman inactive, but the molecular fingerprint of NS1 protein at Raman shift
      1012 cm(-1), which has never been reported before. The distinct peak is
      discovered to be attributed by breathing vibration of the benzene ring structure
      of NS1 side chain molecule. The characteristic peak is also found to vary in
      direct proportion to concentration of the NS1-saliva mixture, with a correlation
      coefficient of +0.96118 and a standard error estimation of 0.11382.

PMID- 24110209
TI  - An optically coupled system for quantitative monitoring of MRI gradient currents
      induced into endocardial leads.
AB  - The time-varying gradient fields generated during Magnetic Resonance Imaging
      (MRI) procedures have the potential to induce electrical current on implanted
      endocardial leads. Whether this current can result in undesired cardiac
      stimulation is unknown. This paper presents an optically coupled system with the
      potential to quantitatively measure the currents induced by the gradient fields
      into endocardial leads during MRI procedures. Our system is based on a
      microcontroller that works as analog-to-digital (A/D) converter and sends the
      current signal acquired from the lead to an optical high-speed light-emitting
      diode transmitter. Plastic fiber guides the light outside the MRI chamber, to a
      photodiode receiver and then to an acquisition board connected to a PC. The
      preliminary characterization of the performances of the system is also presented.

PMID- 24110210
TI  - Finite Element Modeling of scattered electromagnetic waves for stroke analysis.
AB  - Stroke has become one of the leading causes of mortality worldwide and about 800
      in every 100,000 people suffer from stroke each year. The occurrence of stroke is
      ranked third among the causes of acute death and first among the causes for
      neurological dysfunction. Currently, Neurological examinations followed by
      medical imaging with CT, MRI or Angiography are used to provide better
      identification of the location and the type of the stroke, however they are
      neither fast, cost-effective nor portable. Microwave technology has emerged to
      complement these modalities to diagnose stroke as it is sensitive to the
      differences between the distinct dielectric properties of the brain tissues and
      blood. This paper investigates the possibility of diagnosing the type of stroke
      using Finite Element Analysis (FEA). The object of interest is a simulated head
      phantom with stroke, created with its specifying material characteristics like
      electrical conductivity and relative permittivity. The phantom is then placed in
      an electromagnetic field generated by a dipole antenna radiating at 1 GHz. The
      FEM forward model solver computes the scattered electromagnetic field by finding
      the solution for the Maxwell's wave equation in the head volume. Subsequently the
      inverse scattering problem is solved using the Contrast Source Inversion (CSI)
      method to reconstruct the dielectric profile of the head phantom. 

PMID- 24110211
TI  - Comparison of geometric torsion in scoliosis under Lenke classification.
AB  - The objective of this study is to investigate whether three dimensional (3D)
      variability exists within the Lenke classification, and to evaluate the
      correlations between the 3D features and the Cobb angle used in the Lenke
      classification. Forty-nine scoliotic patients with Lenke Type 1 curve were
      selected for analysis. For each patient, the 3D spine model was reconstructed
      from biplanar radiographs, and the geometric torsion was then calculated from the
      reconstructed spine model. An analysis of variance (ANOVA) was performed
      regarding the average torsion, the maximum torsion, and the Cobb angle, with the
      patients subdivided according to the torsion pattern. Results showed that a
      statistically significant difference was observed for the torsion parameters
      (i.e., the average torsion and the maximum torsion) between subgroups within the
      Lenke Type 1 curves while no statistically significant difference was found
      regarding the Cobb angle. The strengths of correlations between the torsion
      parameters and Cobb angle were stronger in the subgroup with torsion pattern of
      Type A. These results add the evidence that 3D geometric torsion reveals
      structural differences that are not apparent in the Cobb measurement. 

PMID- 24110212
TI  - Near-infrared spectroscopy system for determining brain hemoglobin level.
AB  - Traumatic brain injury (TBI) usually results from brain shaking or impact. It can
      affect the normal function of the brain and even cause people become disabled and
      death. However, there is lack of studies for the physiological changes of humans
      or animals under brain injury. In order to obtain the information of
      physiological state change, we designed and enforced a non-invasive, wireless
      multi-channel near-infrared spectroscopy (NIRS) for monitoring the concentration
      change of oxy-hemoglobin (HbO2), deoxy-hemoglobin (HbR) and total-hemoglobin
      (HbT) continuously during and after TBI. The experimental results indicated that
      the concentration change of HbO2 and HbT is significantly related to the impact
      strength and infarction volume. Thus, this system is easily used and stable for
      TBI study. 

PMID- 24110214
TI  - Capturing and analyzing wheelchair maneuvering patterns with mobile cloud
      computing.
AB  - Power wheelchairs have been widely used to provide independent mobility to people
      with disabilities. Despite great advancements in power wheelchair technology,
      research shows that wheelchair related accidents occur frequently. To ensure safe
      maneuverability, capturing wheelchair maneuvering patterns is fundamental to
      enable other research, such as safe robotic assistance for wheelchair users. In
      this study, we propose to record, store, and analyze wheelchair maneuvering data
      by means of mobile cloud computing. Specifically, the accelerometer and gyroscope
      sensors in smart phones are used to record wheelchair maneuvering data in real
      time. Then, the recorded data are periodically transmitted to the cloud for
      storage and analysis. The analyzed results are then made available to various
      types of users, such as mobile phone users, traditional desktop users, etc. The
      combination of mobile computing and cloud computing leverages the advantages of
      both techniques and extends the smart phone's capabilities of computing and data
      storage via the Internet. We performed a case study to implement the mobile cloud
      computing framework using Android smart phones and Google App Engine, a popular
      cloud computing platform. Experimental results demonstrated the feasibility of
      the proposed mobile cloud computing framework. 

PMID- 24110213
TI  - Optically-induced dielectrophoretic technology for cancer cells identification
      and concentration.
AB  - The detection and concentration of cancer cells in peripheral blood is of great
      importance for cancer diagnosis and prognosis. Optically-induced
      dielectrophoresis (ODEP) can achieve high resolution and low optical intensities,
      and the electrodes pattern can be dynamically changed by varied light pattern. In
      this paper, a special lens is used to project the entire image to the ODEP chip
      to achieve 2.6 * 2 mm(2) manipulating area. By changing projected light pattern,
      it is demonstrated to separate 10, 20, and 40 um PS (polystyrene) beads; HT-29,
      20 um PS beads. The MCF-7 cells concentrated experiments are also demo at 100
      um/sec velocity.

PMID- 24110215
TI  - A novel method for monitoring urinary bladder internal pressure: feasibility
      test.
AB  - The study presents a new approach for measuring non-invasively urinary bladder
      internal pressure which can resolve all the shortcomings of existing methods. The
      novel method makes use of acoustic cavitation. The theoretical foundation for the
      proposed technique was presented, together with the preliminary experimental
      validation. The study claims that the proposed novel non-invasive ultrasonic
      urinary bladder internal pressure monitoring is feasible and can be used any time
      regardless of gender, so that it will be of a great benefit to the diagnosis and
      therapy of urination related diseases. 

PMID- 24110216
TI  - Noninvasive monitoring of blood pressure using optical Ballistocardiography and
      Photoplethysmograph approaches.
AB  - A new all optical method for long term and continuous blood pressure measurement
      and monitoring without using cuffs is proposed by using Ballistocardiography
      (BCG) and Photoplethysmograph (PPG). Based on BCG signal and PPG signal, a time
      delay between these two signals is obtained to calculate both systolic blood
      pressure and diastolic blood pressure via linear regression analysis. The
      fabricated noninvasive blood pressure monitoring device consists of a fiber
      sensor mat to measure BCG signal and a SpO2 sensor to measure PPG signal. A
      commercial digital oscillometric blood pressure meter is used to obtain reference
      values and for calibration. It has been found that by comparing with the
      reference device, our prototype has typical means and standard deviations of 9+/
      5.6 mmHg for systolic blood pressure, 1.8+/-1.3 mmHg for diastolic blood pressure
      and 0.6+/-0.9 bpm for pulse rate, respectively. If the fiber optic SpO2 probe is
      used, this new all fiber cuffless noninvasive blood pressure monitoring device
      will truly be a MRI safe blood pressure measurement and monitoring device.

PMID- 24110217
TI  - Wireless remote patient monitoring in older adults.
AB  - Wireless patient monitoring systems are emerging as a low cost, reliable and
      accurate way of healthcare delivery. In this paper we present a wireless remote
      vital sign monitoring system with audio/video data transmission. Vital signs
      include; blood pressure (systolic and diastolic), heart rate, pulse, oxygen
      saturation, body temperature, lungs air volume and blood glucose level. In
      addition, a two-way audio/video communication link connects patients to their
      healthcare providers. The proposed system employs a computer-based software
      application that effectively incorporates current data with electronic medical
      record in order to enhance patient care. We evaluated this system with 10
      individuals for assessing its acceptability by the users and its compatibility
      with other medical devices. A clinical trial with more than 30 participants aged
      over 65 years is also in progress at a local hospital. 

PMID- 24110218
TI  - Measurement and analysis of Vibrio fischeri cell-based microfluidic device for
      personal health monitoring.
AB  - The cell-based microfluidic chip was designed and fabricated as a low-cost
      detector to continuously monitor toxicants in drinking water or human urine
      samples, which is expected to be an important component of a household health
      monitoring system in the future. The bioluminescent bacterium, Vibrio Fischeri,
      was selected to validate the function of device. Water samples and Vibrio
      fischeri cells were mixed and encapsulated into droplets in air flow, which can
      guarantee sufficient oxygen supply for cells in droplets. Preliminary tests were
      performed using copper ion (Cu(2+)) as the model toxicant. The droplet system was
      measured and analyzed at various flow rates in different observation chambers.
      Both deionized water and human urine samples were tested in the cell-based
      device. Interestingly, a strong relation between the R.L.U. (Relative
      Luminescence Units) in the observation chamber and the minute concentration of
      toxicant (Cu(2+)) was found using deionized water as solvent, whereas the
      relation was insignificant using human urine as solvent. This study showed the
      Vibrio fischeri cell-based device might be reliably employed as an early-warning
      system for the safety of drinking water. However, Vibrio fischeri is not
      competent to detect dangerous materials in a complex biofluid. With the
      replacement of cell sensors, the microfluidic device might be functional to
      analyze urine samples in theory. 

PMID- 24110219
TI  - Tidal breathing flow-volume curves with impedance pneumography during expiratory
      loading.
AB  - Diagnosis of asthma in the preschoold children is difficult due to lack of
      objective lung function tests suitable for this age group. Impedance pneumography
      (IP) is a mode of measurement that may potentially enable ambulatory 24h
      recording of tidal breathing indices and respiratory dynamics that are known to
      relate to small airway obstruction. The aim of this research was to induce
      changes in breathing control and mechanics and study the ability of IP to
      reproduce TBFVC and track its changes under potentially difficult conditions.
      This was achieved by a comparison of direct mouth pneumotachograph (PNT) and IP
      tidal breathing flow-volume curves (TBFVC) during free breathing and expiratory
      loading obtained from 17 young lung-healthy subjects. The expiratory loading
      produced strong and significant changes in the respiratory pattern and mouth
      pressure. The agreement of PNT and IP normalized TBFVCs was found excellent
      having the highest distance between the normalized TBFVCs of (mean +/- SD) 7.4 %
      +/- 3.6 % and 6.2 % +/- 3.0 % during free and loaded breathing, respectively. The
      agreement was not affected by the presence of the expiratory load despite it
      poses multiple potential hazards for the IP measurements. We conclude that by
      using correct electrode placement and cardiac filtering, IP was able to
      accurately reproduce and track changes in normalized TBFVCs under normal and
      abnormal respiratory conditions in healthy adult subjects.

PMID- 24110220
TI  - Model-based measurement of gas exchange in healthy subjects using ALPE essential-
      influence of age, posture and gender.
AB  - The ALPE Essential device for model-based measurement of pulmonary gas exchange
      status may be a useful alternative to current methods for diagnosing, monitoring
      and evaluating treatment related to pulmonary gas exchange. In this study, shunt
      and ventilation/perfusion mismatch were measured with ALPE Essential in 106
      healthy subjects with the aim of investigating the influence of age, posture and
      gender on gas exchange parameters and evaluating the test-retest reliability of
      the measurements. Age and gender did not have statistically significant influence
      on gas exchange parameters, although there was a tendency for poorer matching of
      ventilation and perfusion with age. Posture was shown to be important when
      measuring gas exchange parameters. Absolute measurement reliability was
      acceptable with future studies in patients being necessary for accurate
      evaluation of relative reliability.